PMID- 24884828
TI  - BRCA1/2 germline mutations and their clinical importance in Turkish breast cancer
      patients.
AB  - BRCA1/BRCA2 genes were screened in 117 patients with breast cancer by sequencing.
      Fourteen percent of patients tested positive for BRCA1/BRCA2 mutations. Four
      frame shift mutations, four pathogenic missense mutations, and 25 different
      sequence variations were detected. BRCA mutation positivity was significantly
      associated with Ki67 (p = .001). BRCA protein expressions were decreased in the
      patients harboring important mutations and polymorphisms (BRCA1;P508 stop,
      V1740G, Q1182R, Q1756P and BRCA2;V2466A) related with disease. Our findings
      contribute significantly to the types of germline BRCA1/BRCA2 mutations and their
      biological effects in Turkish women. These data could help guide the management
      of BRCA1/BRCA2 mutation-carrying patients when considering breast-conserving
      therapy.

PMID- 24884829
TI  - Changes in PKM2 associate with prostate cancer progression.
AB  - Pyruvate kinase M2 (PKM2) is essential for aerobic glycolysis, the dominant
      metabolic pathway utilized by cancer cells. To determine the association of PKM2
      with prostate cancer (PC), we examined 29 primary PC and three lymph node
      metastatic tumors; elevation of PKM2 was observed in Gleason 8-10 tumors compared
      to Gleason 6-7 carcinomas. High PKM2 was detected by immunohistochemistry in more
      aggressive xenograft tumors derived from PC stem-like cells (PCSCs) compared to
      those produced from non-PCSCs. While PCSCs and non-PCSCs expressed comparable
      levels of PKM2, distinct posttranslational modifications were observed.
      Collectively, upregulation and specific modification to PKM2 associate with PC
      progression.

PMID- 24884830
TI  - Differential expression patterns and clinical significance of estrogen receptor
      alpha and beta in papillary thyroid carcinoma.
AB  - BACKGROUND: The incidence of papillary thyroid cancer (PTC) is markedly higher in
      women than men during the reproductive years. In vitro studies have suggested
      that estrogen may play an important role in the development and progression of
      PTC through estrogen receptors (ERs). This study aimed to investigate the
      expression patterns of the two main ER subtypes, alpha and beta1 (wild-type
      ERbeta), in PTC tissue and their clinical significance. METHODS:
      Immunohistochemical staining of thyroid tissue sections was performed to detect
      ER expression in female patients with PTC (n =89) and nodular thyroid goiter
      (NTG; n =30) using the ElivisionTM plus two-step system. The relationships
      between ER subtype expression and clinicopathological/biological factors were
      further analyzed. RESULTS: The positive percentage and expression levels of
      ERalpha were significantly higher in female PTC patients of reproductive age (18
      45 years old; n =50) than age-matched female NTG patients (n =30), while ERbeta1
      exhibited the opposite pattern. There was no difference in ERalpha or ERbeta1
      expression between female PTC patients of reproductive age and those of advanced
      reproductive age (>45 years old; n =39). In the female PTC patients of
      reproductive age, ERalpha expression level was positively correlated with that of
      Ki-67, while ERbeta1 was negatively correlated with mutant P53. Furthermore, more
      patients with exclusively nuclear ERalpha expression had extrathyroidal extension
      (ETE) as compared with those with extranuclear ERalpha localization. VEGF
      expression was significantly decreased in female PTC patients of reproductive age
      with only nuclear ERbeta1 expression when compared with those with extranuclear
      ERbeta1 localization. In PTC patients of advanced reproductive age, neither
      ERalpha nor ERbeta1 expression showed any correlation with that of Ki-67, mutant
      P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases. CONCLUSIONS: The
      differential expression patterns of the two ER subtypes between PTC and NTG
      indicate that ERalpha may be a useful immunohistochemical marker for differential
      diagnosis of PTC. The associations of ER subtype expression with Ki-67, mutant
      P53, VEGF expression and ETE in female PTC patients of reproductive age suggest
      that estrogen-activated ERalpha may mediate stimulatory effects on PTC growth and
      progression whereas ERbeta1 has some inhibitory actions.

PMID- 24884831
TI  - Aggressive middle turbinate osteoblastoma with intracranial extension: a case
      report.
AB  - INTRODUCTION: Osteoblastoma is an uncommon benign bone tumor that accounts for 1
      percent of all primary bone tumors. About 30 to 40 percent of all osteoblastoma
      cases involve the spine. Osteoblastoma involving the nasal cavity is rare, with
      only 11 reported cases in the English-language literature, while only four cases
      of turbinate osteoblastoma have been described. CASE PRESENTATION: We report an
      unusual case of middle turbinate osteoblastoma associated with right-sided nasal
      obstruction and severe headache in a 14-year-old Caucasian girl. The tumor
      involved the right middle turbinate, complete anterior and incomplete posterior
      ethmoidal cells, and the frontal sinus ostium. Cribriform lamina was, in the most
      part, consumed by the tumor growth, while the skull base was mostly of normal
      bone structure. CONCLUSIONS: To the best of our knowledge, this is the first case
      of middle turbinate osteoblastoma with intracranial spread. Surgical treatment is
      the only therapeutic option for osteoblastoma.

PMID- 24884832
TI  - Adolescent outcomes and opportunities in a Canadian province: looking at siblings
      and neighbors.
AB  - BACKGROUND: Well-organized administrative data with large numbers of cases
      (building on linked files from several government departments) and a population
      registry facilitate new studies of population health and child development.
      Analyses of family relationships and a number of outcomes--educational
      achievement, health, teen pregnancy, and receipt of income assistance--are
      relatively easy to conduct using several birth cohorts. Looking both at
      means/proportions and at sibling correlations enriches our study of opportunity
      and well-being in late adolescence. With observational research possibly
      exaggerating the causal effects of risk factors, sibling comparisons involving
      individuals sharing both many family characteristics and many genes help deal
      with such criticisms. METHODS: This paper uses a rich dataset from one Canadian
      province (Manitoba) covering a wide range of geographical areas (cities to rural
      regions). Influences on opportunity and well-being are analyzed looking at both
      means/proportions and sibling correlations. We measure a variety of outcomes that
      may reflect different causal influences. A creative application of linear
      programming advances the use of data on residential location. RESULTS: Predicting
      educational achievement using available variables was much easier than predicting
      adolescent health status (R-square of .200 versus R-square of .043). Low levels
      of educational achievement, high levels of teenage pregnancy, and high sibling
      correlations outside Winnipeg and within Winnipeg's lower income areas highlight
      inequalities across socioeconomic and geographic backgrounds. Stratifying our
      analyses by different variables, such as income quintiles, reveals differences in
      means and correlations within outcomes and across groups. Particular events-
      changes in mother's marital status and in place of residence--were associated
      with less favorable outcomes in late adolescence. CONCLUSION: Our findings
      suggest a paradox: Canadian developmental outcomes through late adolescence
      appear quite similar to those in the United States, even though intergenerational
      mobility in Canada is closer to mobility in the Nordic countries than to that in
      the United States.

PMID- 24884833
TI  - Regional differences in acute corticosterone-induced dendritic remodeling in the
      rat brain and their behavioral consequences.
AB  - BACKGROUND: Glucocorticoid released by stressful stimuli elicits various stress
      responses. Acute treatment with a single dose of corticosterone (CORT;
      predominant glucocorticoid of rats) alone has previously been shown to trigger
      anxiety behavior and robust dendritic hypertrophy of neurons in the basolateral
      amygdala (BLA). Neurons in the medial prefrontal cortex (mPFC) are also known to
      be highly sensitive to stress and regulate anxiety-like behaviors. Nevertheless,
      we know less about acute CORT-induced structural changes of other brain regions
      and their behavioral outcomes. In addition, the temporal profile of acute CORT
      effects remains to be examined. The current study investigates time course
      changes of dendritic architectures in the stress vulnerable brain areas, the BLA
      and mPFC, and their behavioral consequences after acute treatment with a single
      dose of CORT. RESULTS: Acute CORT treatment produced delayed onset of dendritic
      remodeling in the opposite direction in the BLA and mPFC with different time
      courses. Acute CORT induced dendritic hypertrophy of BLA spiny neurons, which was
      paralleled by heightened anxiety, both peaked 12 days after the treatment.
      Meanwhile, CORT-induced dendritic atrophy of mPFC pyramidal neurons peaked on day
      6, concomitantly with impaired working memory. Both changed dendritic
      morphologies and altered behavioral outcomes were fully recovered. CONCLUSION:
      Our results suggest that stress-induced heightened anxiety appears to be a
      functional consequence of dendritic remodeling of BLA neurons but not that of
      mPFC. Instead, stress-induced dendritic atrophy of mPFC neurons is relevant to
      working memory deficit. Therefore, structural changes in the BLA and the mPFC
      might be specifically associated with distinct behavioral symptoms observed in
      stress-related mental disorders. Remarkably, stress-induced dendritic remodeling
      in the BLA as well as mPFC is readily reversible. The related behavioral outcomes
      also follow the similar time course in a reversible manner. Therefore, further
      studies on the cellular mechanism for the plasticity of dendrites architecture
      might provide new insight into the etiological factors for stress-related mental
      illness such as posttraumatic stress disorder (PTSD).

PMID- 24884834
TI  - Increased ethanol accumulation from glucose via reduction of ATP level in a
      recombinant strain of Saccharomyces cerevisiae overexpressing alkaline
      phosphatase.
AB  - BACKGROUND: The production of ethyl alcohol by fermentation represents the
      largest scale application of Saccharomyces cerevisiae in industrial
      biotechnology. Increased worldwide demand for fuel bioethanol is anticipated over
      the next decade and will exceed 200 billion liters from further expansions. Our
      working hypothesis was that the drop in ATP level in S. cerevisiae cells during
      alcoholic fermentation should lead to an increase in ethanol production (yield
      and productivity) with a greater amount of the utilized glucose converted to
      ethanol. Our approach to achieve this goal is to decrease the intracellular ATP
      level via increasing the unspecific alkaline phosphatase activity. RESULTS:
      Intact and truncated versions of the S. cerevisiae PHO8 gene coding for vacuolar
      or cytosolic forms of alkaline phosphatase were fused with the alcohol
      dehydrogenase gene (ADH1) promoter. The constructed expression cassettes used for
      transformation vectors also contained the dominant selective marker kanMX4 and S.
      cerevisiae delta-sequence to facilitate multicopy integration to the genome.
      Laboratory and industrial ethanol producing strains BY4742 and AS400
      overexpressing vacuolar form of alkaline phosphatase were characterized by a
      slightly lowered intracellular ATP level and biomass accumulation and by an
      increase in ethanol productivity (13% and 7%) when compared to the parental
      strains. The strains expressing truncated cytosolic form of alkaline phosphatase
      showed a prolonged lag-phase, reduced biomass accumulation and a strong defect in
      ethanol production. CONCLUSION: Overexpression of vacuolar alkaline phosphatase
      leads to an increased ethanol yield in S. cerevisiae.

PMID- 24884835
TI  - Relationship between clinical and surgical findings and reparability of large and
      massive rotator cuff tears: a longitudinal study.
AB  - BACKGROUND: The literature has shown good results with partial repairs of large
      and massive tears of rotator cuff but the role of factors that affect
      reparability is less clear. The purpose of this study was twofold, 1) to examine
      clinical outcomes following complete or partial repair of large or massive full
      thickness rotator cuff tear, and 2) to explore the value of clinical and surgical
      factors in predicting reparability. METHODS: This was a secondary data analysis
      of consecutive patients with large or massive rotator cuff tear who required
      surgical treatment (arthroscopic complete or partial repair) and were followed up
      for two years. Disability measures included the American Shoulder and Elbow
      Surgeons (ASES), the relative Constant-Murley score (CMS) and the shortened
      version of the Western Ontario Rotator Cuff Index (ShortWORC). The relationship
      between predictors and reparability was examined through logistic regressions and
      chi-square statistics as appropriate. Within group change over time and between
      group differences in disability outcomes, range of motion and strength were
      examined by student's T-tests and non-parametric statistics. RESULTS: One hundred
      and twenty two patients (41 women, 81 men, mean age 64, SD=9) were included in
      the analysis. There were 86 large (39 fully reparable, 47 partially reparable)
      and 36 (10 fully reparable, 26 partially reparable) massive tears. Reparability
      was not associated with age, sex, or pre-operative active flexion or abduction
      (p0>0.05) but the fully reparable tear group showed a better pre-operative ASES
      score (p=0.01) and better active external rotation in neutral (p=0.01).
      Reparability was associated with tear shape (p<0.0001), size (p=0.002), and
      tendon quality (p<0.0001). CONCLUSIONS: Reparability of large or massive tears is
      affected by a number of clinical and surgical factors. Patients whose tears could
      not be fully repaired showed a statistically significant improvement in range of
      motion, strength and disability at 2 years, although they had slightly inferior
      results compared to those with complete repairs.

PMID- 24884836
TI  - Quality of life after the initial treatments of non-small cell lung cancer: a
      persistent predictor for patients' survival.
AB  - BACKGROUND: Health-related quality of life (HRQoL) before treatment may predict
      survival of patients with non-small-cell lung cancer (NSCLC). We investigated the
      predictive role of HRQoL after the initial treatments, on the survival of these
      patients. METHODS: A prospective multi-center study conducted in northeastern
      France. The SF-36 and European Organization for Research and Treatment of Cancer,
      Quality of Life Questionnaire Core-30 (QLQ C-30) were mailed to patients 3 months
      after the end of the diagnostic process. High scores for functioning dimensions
      on both questionnaires indicated better QoL, and low scores for symptom
      dimensions on the QLQ C-30 indicated few symptoms. Cox regression modeling was
      used to identify predictive factors of survival. RESULTS: In total, 230 (63.5%)
      patients responded to the SF-36 and QLQ C-30. Before completing the
      questionnaires, almost 60% of patients had undergone some chemotherapy, about 10%
      underwent radio/chemotherapy or both and more than 30% underwent surgery or
      surgery plus chemo/radiotherapy. On SF-36, the highest mean score was for social
      functioning dimension (55.5 +/- 28), and the lowest was for the physical role
      dimension (17.9 +/- 32.2). On QLQ C-30, for the functioning dimensions, the
      highest mean score was for cognitive functioning (74.6 +/- 25.9) and the lowest
      was for role functioning (47.2 +/- 34.1). For symptom dimensions, the lowest
      score was for diarrhoea (11.5 +/- 24.2) and the highest was for fatigue (59.7 +/-
      27.7). On multivariate analysis, high bodily pain, social functioning and general
      health scores (SF-36) were associated with a lower risk of death (hazard ratio
      0.580; 95% confidence interval [0.400-0.840], p = 0.004; HR 0.652 [0.455-0.935],
      p < 0.02; HR 0.625 [0.437-0.895] respectively). Better general QoL on QLQ C-30
      was related to lower risk of death (HR 0.689 [0.501-0.946], p = 0.02).
      CONCLUSION: Adding to previous knowledge about factors that may influence
      patients QoL, this study shows a persisting relationship between better perceived
      health in HRQoL after the initial treatment of NSCLC and better survival.

PMID- 24884837
TI  - Type three secretion system-mediated escape of Burkholderia pseudomallei into the
      host cytosol is critical for the activation of NFkappaB.
AB  - BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, a
      potentially fatal disease endemic in Southeast Asia and Northern Australia. This
      Gram-negative pathogen possesses numerous virulence factors including three
      "injection type" type three secretion systems (T3SSs). B. pseudomallei has been
      shown to activate NFkappaB in HEK293T cells in a Toll-like receptor and MyD88
      independent manner that requires T3SS gene cluster 3 (T3SS3 or T3SSBsa). However,
      the mechanism of how T3SS3 contributes to NFkappaB activation is unknown.
      RESULTS: Known T3SS3 effectors are not responsible for NFkappaB activation.
      Furthermore, T3SS3-null mutants are able to activate NFkappaB almost to the same
      extent as wildtype bacteria at late time points of infection, corresponding to
      delayed escape into the cytosol. NFkappaB activation also occurs when bacteria
      are delivered directly into the cytosol by photothermal nanoblade injection.
      CONCLUSIONS: T3SS3 does not directly activate NFkappaB but facilitates bacterial
      escape into the cytosol where the host is able to sense the presence of the
      pathogen through cytosolic sensors leading to NFkappaB activation.

PMID- 24884838
TI  - Comparison of AMG 416 and cinacalcet in rodent models of uremia.
AB  - BACKGROUND: AMG 416 is a novel peptide agonist of the calcium-sensing receptor
      (CaSR). This report describes the activity of AMG 416 in two different rodent
      models of uremia, compared in each case to cinacalcet, an approved therapeutic
      for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease
      on dialysis. METHODS: AMG 416 was administered as a single intravenous (IV) bolus
      in a severe, acute model of renal insufficiency (the "1K1C" model) and plasma
      parathyroid hormone (PTH) and serum calcium levels were monitored for 24 hours.
      In a chronic, less severe model of renal dysfunction, the 5/6 nephrectomy (5/6
      Nx) model, AMG 416 was administered as a once-daily IV bolus for 28 days. Both
      studies included a control (vehicle) group and a comparison cinacalcet group (po
      dosing at 30 mg/kg and 10 mg/kg for the 1K1C and 5/6 Nx studies, respectively).
      RESULTS: Administration of AMG 416 by IV bolus injection into rats with acute
      renal dysfunction (1K1C model) resulted in a sustained reduction in plasma PTH
      from the initial elevated values. Following a single IV bolus (0.5 mg/kg), AMG
      416 caused a substantial drop in PTH levels which remained approximately 50%
      below their initial level at 24 hrs. In the same model, oral treatment with
      cinacalcet (30 mg/kg) resulted in an acute drop in PTH which almost returned to
      the starting level by 24 hours after dosing. In the 5/6 Nx chronic uremia model,
      daily IV dosing of AMG 416 over 4 weeks (1 mg/kg) resulted in a sustained
      reduction in PTH, with approximately 50% of the initial level observed 48 hours
      post treatment throughout the study. Cinacalcet treatment (10 mg/kg) in the same
      model resulted in acutely lowered plasma PTH levels which returned to placebo
      levels by 24 hours post-dose. Consistent with the reductions in plasma PTH,
      reductions in serum calcium were observed in both AMG 416- and cinacalcet-treated
      animals. CONCLUSIONS: As a long-acting CaSR agonist suitable for administration
      by the IV route, AMG 416 is a potential new therapy for the treatment of CKD
      patients with SHPT receiving hemodialysis.

PMID- 24884840
TI  - Recurrent erysipelas--risk factors and clinical presentation.
AB  - BACKGROUND: Erysipelas is a common infection that often recurs, but the impact of
      specific risk factors for reoccurrence remains elusive. In the present study we
      aimed at clarifying predisposing conditions for reoccurrence. METHODS: Medical
      records were reviewed from all patients >=18 years of age diagnosed with
      erysipelas at the Department of Infectious Diseases at Skane University Hospital,
      Sweden, from January 2007 to February 2011. 502 patients were included, of which
      357 were single episode erysipelas and 145 had recurrent erysipelas. These two
      groups were compared regarding underlying conditions and clinical presentation.
      RESULTS: Erysipelas in the lower limbs had the greatest propensity of recurrence.
      The associations between underlying conditions and recurrence were largely
      depending on the site of erysipelas. Overall, the most prominent risk factor for
      recurrence was lymphedema and other conditions causing a chronic impairment of
      the defence against microbes. Conditions temporarily disrupting the skin barrier
      (e.g. a local wound or toe web intertrigo), although likely being risk factors
      for erysipelas per se, did not seem to predispose to repeated episodes.
      Individuals with recurrent erysipelas tended to seek medical attention earlier,
      and were less likely to be hospitalized or receive intravenous antibiotics, but
      there was no evidence of any difference in inflammatory reaction when taking
      confounding factors into account. CONCLUSIONS: In this large cross-sectional
      study of over 500 patients with erysipelas, lymphedema was the most prominent
      risk factors for recurrence although the distribution of predisposing conditions
      varies depending on the site of erysipelas.

PMID- 24884839
TI  - The Netrin-1 receptor DCC is a regulator of maladaptive responses to chronic
      morphine administration.
AB  - BACKGROUND: Opioids are the cornerstone of treatment for moderate to severe pain,
      but chronic use leads to maladaptations that include: tolerance, dependence and
      opioid-induced hyperalgesia (OIH). These responses limit the utility of opioids,
      as well as our ability to control chronic pain. Despite decades of research, we
      have no therapies or proven strategies to overcome this problem. However, murine
      haplotype based computational genetic mapping and a SNP data base generated from
      analysis of whole-genome sequence data (whole-genome HBCGM), provides a
      hypothesis-free method for discovering novel genes affecting opioid maladaptive
      responses. RESULTS: Whole genome-HBCGM was used to analyze phenotypic data on
      morphine-induced tolerance, dependence and hyperalgesia obtained from 23 inbred
      strains. The robustness of the genetic mapping results was analyzed using strain
      subsets. In addition, the results of analyzing all of the opioid-related traits
      together were examined. To characterize the functional role of the leading
      candidate gene, we analyzed transgenic animals, mRNA and protein expression in
      behaviorally divergent mouse strains, and immunohistochemistry in spinal cord
      tissue. Our mapping procedure identified the allelic pattern within the netrin-1
      receptor gene (Dcc) as most robustly associated with OIH, and it was also
      strongly associated with the combination of the other maladaptive opioid traits
      analyzed. Adult mice heterozygous for the Dcc gene had significantly less
      tendency to develop OIH, become tolerant or show evidence of dependence after
      chronic exposure to morphine. The difference in opiate responses was shown not to
      be due to basal or morphine-stimulated differences in the level of Dcc expression
      in spinal cord tissue, and was not associated with nociceptive neurochemical or
      anatomical alterations in the spinal cord or dorsal root ganglia in adult
      animals. CONCLUSIONS: Whole-genome HBCGM is a powerful tool for identifying genes
      affecting biomedical traits such as opioid maladaptations. We demonstrate that
      Dcc affects tolerance, dependence and OIH after chronic opioid exposure, though
      not through simple differences in expression in the adult spinal cord.

PMID- 24884841
TI  - Higher incidence of premenopausal breast cancer in less developed countries; myth
      or truth?
AB  - BACKGROUND: Fundamental etiologic differences have been suggested to cause
      earlier onset of breast cancer in less developed countries (LDCs) than in more
      developed countries (MDCs). We explored this hypothesis using world-wide breast
      cancer incidence data. METHODS: We compared international age-standardized
      incidence rates (ASR) of pre- (<50 years) and postmenopausal (>=50 years) breast
      cancers as well as temporal trends in ASRs of pre-and postmenopausal breast
      cancer among selected countries during 1975-2008. We used joinpoint log-linear
      regression analysis to estimate annual percent changes (APC) for premenopausal
      and postmenopausal breast cancer in the northern Europe and in Black and White
      women population in the US. RESULTS: Premenopausal breast cancers comprised a
      substantially higher proportion of all incident breast cancers in LDCs (average
      47.3%) compared to MDCs (average 18.5%). However, the ASR of premenopausal breast
      cancer was consistently higher in MDCs (29.4/100,000) than LDCs (12.8/100,000).
      The ASR of postmenopausal cancer was about five-fold higher in the MDCs
      (307.6/100,000) than the LDCs (65.4/100,000). The APC of breast cancer in Denmark
      was substantially higher in postmenopausal (1.33%) than premenopausal cancer
      (0.98%). Higher incidence of breast cancer among the white than black women in
      the US was pertained only to the postmenopausal cancer. CONCLUSION: The
      substantial and consistent lower age-specific incidence of breast cancer in LDCs
      than in MDCs contradicts the theory of earlier onset. Demographic differences
      with fewer old women in LDCs and lower prevalence of risk factors of
      postmenopausal cancer are the most likely explanation to the lower mean age at
      diagnosis in these countries.

PMID- 24884842
TI  - Urinary soluble urokinase receptor levels are elevated and pathogenic in patients
      with primary focal segmental glomerulosclerosis.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a major cause of end
      stage renal disease. Recent studies have proposed that plasma soluble urokinase
      receptor (suPAR) might be a causative circulating factor but this proposal has
      caused controversy. This study aimed to measure urinary suPAR levels in patients
      with primary FSGS and its significance in the pathogenesis of FSGS. METHODS:
      Sixty-two patients with primary FSGS, diagnosed between January 2006 and January
      2012, with complete clinical and pathologic data were enrolled, together with
      disease and normal controls. Urinary suPAR levels were measured using commercial
      ELISA kits and were corrected by urinary creatinine (Cr). The associations
      between urinary suPAR levels and clinical data at presentation and during follow
      up were analyzed. Conditionally immortalized human podocytes were used to study
      the effect of urinary suPAR on activating beta3 integrin detected by AP5
      staining. RESULTS: The urinary suPAR level of patients with primary FSGS (500.56,
      IQR 262.78 to 1,059.44 pg/MUmol Cr) was significantly higher than that of
      patients with minimal change disease (307.86, IQR 216.54 to 480.18 pg/MUmol Cr, P
      = 0.033), membranous nephropathy (250.23, IQR 170.37 to 357.59 pg/MUmol Cr, P
      <0.001), secondary FSGS (220.45, IQR 149.38 to 335.54 pg/MUmol Cr, P <0.001) and
      normal subjects (183.59, IQR 103.92 to 228.78 pg/MUmol Cr, P <0.001). The urinary
      suPAR level of patients with cellular variant was significantly higher than that
      of patients with tip variant. The urinary suPAR level in the patients with
      primary FSGS was positively correlated with 24-hour urine protein (r = 0.287, P =
      0.024). During follow up, the urinary suPAR level of patients with complete
      remission decreased significantly (661.19, IQR 224.32 to 1,115.29 pg/MUmol Cr
      versus 217.68, IQR 121.77 to 415.55 pg/MUmol Cr, P = 0.017). The AP5 signal was
      strongly induced along the cell membrane when human differentiated podocytes were
      incubated with the urine of patients with FSGS at presentation, and the signal
      could be reduced by a blocking antibody specific to uPAR. CONCLUSIONS: Urinary
      suPAR was specifically elevated in patients with primary FSGS and was associated
      with disease severity. The elevated urinary suPAR could activate beta3 integrin
      on human podocytes.

PMID- 24884843
TI  - The role of ribonucleases in regulating global mRNA levels in the model organism
      Thermus thermophilus HB8.
AB  - BACKGROUND: RNA metabolism, including RNA synthesis and RNA degradation, is one
      of the most conserved biological systems and has been intensively studied;
      however, the degradation network of ribonucleases (RNases) and RNA substrates is
      not fully understood. RESULTS: The genome of the extreme thermophile, Thermus
      thermophilus HB8 includes 15 genes that encode RNases or putative RNases. Using
      DNA microarray analyses, we examined the effects of disruption of each RNase on
      mRNA abundance. Disruption of the genes encoding RNase J, RecJ-like protein and
      RNase P could not be isolated, indicating that these RNases are essential for
      cell viability. Disruption of the TTHA0252 gene, which was not previously
      considered to be involved in mRNA degradation, affected mRNA abundance, as did
      disruption of the putative RNases, YbeY and PhoH-like proteins, suggesting that
      they have RNase activity. The effects on mRNA abundance of disruption of several
      RNase genes were dependent on the phase of cell growth. Disruption of the RNase Y
      and RNase HII genes affected mRNA levels only during the log phase, whereas
      disruption of the PhoH-like gene affected mRNA levels only during the stationary
      phase. Moreover, disruption of the RNase R and PNPase genes had a greater impact
      on mRNA abundance during the stationary phase than the log phase, whereas the
      opposite was true for the TTHA0252 gene disruptant. Similar changes in mRNA
      levels were observed after disruption of YbeY or PhoH-like genes. The changes in
      mRNA levels in the bacterial Argonaute disruptant were similar to those in the
      RNase HI and RNase HII gene disruptants, suggesting that bacterial Argonaute is a
      functional homolog of RNase H. CONCLUSION: This study suggests that T.
      thermophilus HB8 has 13 functional RNases and that each RNase has a different
      function in the cell. The putative RNases, TTHA0252, YbeY and PhoH-like proteins,
      are suggested to have RNase activity and to be involved in mRNA degradation. In
      addition, PhoH-like and YbeY proteins may act cooperatively in the stationary
      phase. This study also suggests that endo-RNases function mainly during the log
      phase, whereas exo-RNases function mainly during the stationary phase. RNase HI
      and RNase HII may have similar substrate selectivity.

PMID- 24884844
TI  - PhenoVar: a phenotype-driven approach in clinical genomics for the diagnosis of
      polymalformative syndromes.
AB  - BACKGROUND: We propose a phenotype-driven analysis of encrypted exome data to
      facilitate the widespread implementation of exome sequencing as a clinical
      genetic screening test.Twenty test-patients with varied syndromes were selected
      from the literature. For each patient, the mutation, phenotypic data, and genetic
      diagnosis were available. Next, control exome-files, each modified to include one
      of these twenty mutations, were assigned to the corresponding test-patients.
      These data were used by a geneticist blinded to the diagnoses to test the
      efficiency of our software, PhenoVar. The score assigned by PhenoVar to any
      genetic diagnosis listed in OMIM (Online Mendelian Inheritance in Man) took into
      consideration both the patient's phenotype and all variations present in the
      corresponding exome. The physician did not have access to the individual
      mutations. PhenoVar filtered the search using a cut-off phenotypic match
      threshold to prevent undesired discovery of incidental findings and ranked the
      OMIM entries according to diagnostic score. RESULTS: When assigning the same
      weight to all variants in the exome, PhenoVar predicted the correct diagnosis in
      10/20 patients, while in 15/20 the correct diagnosis was among the 4 highest
      ranked diagnoses. When assigning a higher weight to variants known, or
      bioinformatically predicted, to cause disease, PhenoVar's yield increased to
      14/20 (18/20 in top 4). No incidental findings were identified using our cut-off
      phenotypic threshold. CONCLUSION: The phenotype-driven approach described could
      render widespread use of ES more practical, ethical and clinically useful. The
      implications about novel disease identification, advancement of complex diseases
      and personalized medicine are discussed.

PMID- 24884845
TI  - A model-based analysis: what potential could there be for a S. aureus vaccine in
      a hospital setting on top of other preventative measures?
AB  - BACKGROUND: Over the past decade, there has been sustained interest and efforts
      to develop a S. aureus vaccine. There is a need to better evaluate the potential
      public health impact of S. aureus vaccination, particularly given that
      preventative measures exist to reduce infection. To our knowledge, there is no
      previous work to assess the potential of a S. aureus vaccine to yield additional
      MRSA infection reduction in a hospital setting, on top of other preventative
      measures that already proved efficient. METHODS: The main objectives were to
      propose a versatile simulation framework for assessing potential added benefits
      of a hypothetical S. Aureus vaccine in conjunction with other preventative
      measures, and to illustrate possibilities in a given hospital setting. To this
      end, we employed a recently published dynamic transmission modelling framework
      that we further adapted and expanded to include a hypothetical S. aureus
      vaccination component in order to estimate potential benefits of vaccinating
      patients prior to hospital admission. RESULTS: Model-based projections indicate
      that even with other hygiene prevention measures in place, vaccination of
      patients prior to hospital admission has the potential to provide additional
      reduction of MRSA infection. Vaccine coverage and vaccine efficacy are key
      factors that would ultimately impact the magnitude of this reduction. For
      example, in an average case scenario with 50% decolonization, 50% screening and
      50% hygiene compliance level in place, S. aureus vaccination with 25% vaccine
      coverage, 75% vaccine efficacy against infection, and 0% vaccine efficacy against
      colonization, may lead to 12% model-projected additional reduction in MRSA
      infection prevalence due to vaccination, while this reduction could reach 37% for
      vaccination with 75% vaccine coverage and 75% vaccine efficacy against infection
      in the same average case scenario. CONCLUSIONS: S. aureus vaccination could
      potentially provide additional reduction of MRSA infection in a hospital setting,
      on top of reductions from hygiene prevention measures. The magnitude of such
      additional reductions can vary significantly depending on the level of hygiene
      prevention measures in place, as well as key vaccine factors such as coverage and
      efficacy. Identifying appropriate combinations of preventative measures may lead
      to optimal strategies to effectively reduce MRSA infection in hospitals.

PMID- 24884846
TI  - Automated ensemble assembly and validation of microbial genomes.
AB  - BACKGROUND: The continued democratization of DNA sequencing has sparked a new
      wave of development of genome assembly and assembly validation methods. As
      individual research labs, rather than centralized centers, begin to sequence the
      majority of new genomes, it is important to establish best practices for genome
      assembly. However, recent evaluations such as GAGE and the Assemblathon have
      concluded that there is no single best approach to genome assembly. Instead, it
      is preferable to generate multiple assemblies and validate them to determine
      which is most useful for the desired analysis; this is a labor-intensive process
      that is often impossible or unfeasible. RESULTS: To encourage best practices
      supported by the community, we present iMetAMOS, an automated ensemble assembly
      pipeline; iMetAMOS encapsulates the process of running, validating, and selecting
      a single assembly from multiple assemblies. iMetAMOS packages several leading
      open-source tools into a single binary that automates parameter selection and
      execution of multiple assemblers, scores the resulting assemblies based on
      multiple validation metrics, and annotates the assemblies for genes and
      contaminants. We demonstrate the utility of the ensemble process on 225
      previously unassembled Mycobacterium tuberculosis genomes as well as a
      Rhodobacter sphaeroides benchmark dataset. On these real data, iMetAMOS reliably
      produces validated assemblies and identifies potential contamination without user
      intervention. In addition, intelligent parameter selection produces assemblies of
      R. sphaeroides comparable to or exceeding the quality of those from the GAGE-B
      evaluation, affecting the relative ranking of some assemblers. CONCLUSIONS:
      Ensemble assembly with iMetAMOS provides users with multiple, validated
      assemblies for each genome. Although computationally limited to small or mid
      sized genomes, this approach is the most effective and reproducible means for
      generating high-quality assemblies and enables users to select an assembly best
      tailored to their specific needs.

PMID- 24884847
TI  - Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and
      bilateral brainstem lesions.
AB  - BACKGROUND: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly
      in complex I genes, have been associated with variably overlapping phenotypes of
      Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with
      stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first
      case in which the m.4171C>A/MT-ND1 mutation, previously reported only in
      association with LHON, leads also to a Leigh-like phenotype. CASE PRESENTATION: A
      16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo
      associated with bilateral brainstem lesions affecting the vestibular nuclei. His
      mother and one sister also presented subacute visual loss compatible with LHON.
      Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1
      mutation, previously associated with pure LHON, on a haplogroup H background.
      Three additional non-synonymous homoplasmic transitions affecting ND2
      (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits,
      well recognized as polymorphisms in other mtDNA haplogroups but never found on
      the haplogroup H background, were also present. CONCLUSION: This case widens the
      phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also
      lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of
      other ND non-synonymous variants, found outside of their usual mtDNA backgrounds,
      may have increased the pathogenic potential of the primary LHON mutation.

PMID- 24884848
TI  - Single dental implant retained mandibular complete dentures--influence of the
      loading protocol: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Over the years, there has been a strong consensus in dentistry that
      at least two implants are required to retain a complete mandibular denture. It
      has been shown in several clinical trials that one single median implant can
      retain a mandibular overdenture sufficiently well for up to 5 years without
      implant failures, when delayed loading was used. However, other trials have
      reported conflicting results with in part considerable failure rates when
      immediate loading was applied. Therefore it is the purpose of the current
      randomized clinical trial to test the hypothesis that immediate loading of a
      single mandibular midline implant with an overdenture will result in a comparable
      clinical outcome as using the standard protocol of delayed loading.
      METHODS/DESIGN: This prospective nine-center randomized controlled clinical trial
      is still ongoing. The final patient will complete the trial in 2016. In total,
      180 edentulous patients between 60 and 89 years with sufficient complete dentures
      will receive one median implant in the edentulous mandible, which will retain the
      existing complete denture using a ball attachment. Loading of the median implant
      is either immediately after implant placement (experimental group) or delayed by
      3 months of submerged healing at second-stage surgery (control group). Follow-up
      of patients will be performed for 24 months after implant loading. The primary
      outcome measure is non-inferiority of implant success rate of the experimental
      group compared to the control group. The secondary outcome measures encompass
      clinical, technical and subjective variables. The study was funded by the
      Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1).
      DISCUSSION: This multi-center clinical trial will give information on the ability
      of a single median implant to retain a complete mandibular denture when
      immediately loaded. If viable, this treatment option will strongly improve
      everyday dental practice. TRIAL REGISTRATION: The trial has been registered at
      Deutsches Register Klinischer Studien (German register of clinical trials) under
      DRKS-ID: DRKS00003730 since 23 August 2012. (http://www.germanctr.de).

PMID- 24884849
TI  - Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co
      presented on whole inactivated influenza vaccines.
AB  - BACKGROUND: Potent and safe adjuvants are needed to improve the efficacy of
      parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have
      all proven to be effective immunomodulatory adjuvants when administered with a
      variety of antigens. We have previously evaluated the efficacy of membrane
      anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing
      Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge.
      FINDINGS: Here, we describe studies evaluating the parenteral and mucosal
      adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice.
      Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine
      (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral
      lung burden following challenge compared to control WIV vaccinated animals. Both
      IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum
      and nasal washes. CONCLUSIONS: This study highlights for the first time the
      mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting
      mucosal immune responses and reducing viral lung burden. The co-presentation of
      immunomodulators in direct context with viral antigen in whole inactivated viral
      vaccines may provide a means to significantly lower the dose of vaccine required
      for protection.

PMID- 24884851
TI  - The role of private health providers in HIV testing: analysis of data from 18
      countries.
AB  - INTRODUCTION: HIV testing and counseling is a critical component of the overall
      response to the HIV epidemic in low and middle income countries. To date, little
      attention has been paid to the role of private for-profit providers in HIV
      testing. METHODS: We use data from Demographic and Health Surveys and AIDS
      Indicators Surveys to explore the extent to which this sector provides HIV
      testing in 18 developing countries. RESULTS: We find that use of the private
      sector for HIV testing varies significantly by country, with private for-profit
      providers playing a significant role in some countries and a relatively minor one
      in others. At the country level, use of private providers for HIV testing is
      correlated with use of private providers for other health services yet, in many
      countries, significant differences between use of the private sector for HIV
      testing and other services exist. Within countries, we find that wealth is
      strongly associated with use of the private sector for HIV testing in most
      countries, but the relative socio-economic profile of clients who receive an HIV
      test from a private provider varies considerably across countries. On the one
      measure of quality to which we have access, reported adherence to antenatal care
      testing guidelines, there are no statistically significant differences in
      performance between public and private for-profit providers in most countries
      after controlling for wealth. CONCLUSIONS: These results suggest that strategies
      for supervising and engaging private health providers with regard to HIV testing
      should be country specific and take into account local context.

PMID- 24884850
TI  - Nerve growth factor improves functional recovery by inhibiting endoplasmic
      reticulum stress-induced neuronal apoptosis in rats with spinal cord injury.
AB  - BACKGROUND: Endoplasmic reticulum (ER) stress-induced apoptosis plays a major
      role in various diseases, including spinal cord injury (SCI). Nerve growth factor
      (NGF) show neuroprotective effect and improve the recovery of SCI, but the
      relations of ER stress-induced apoptosis and the NGF therapeutic effect in SCI
      still unclear. METHODS: Young adult female Sprague-Dawley rats's vertebral column
      was exposed and a laminectomy was done at T9 vertebrae and moderate contusion
      injuries were performed using a vascular clip. NGF stock solution was diluted
      with 0.9% NaCl and administered intravenously at a dose of 20 MUg/kg/day after
      SCI and then once per day until they were executed. Subsequently, the rats were
      executed at 1d, 3 d, 7d and 14d. The locomotor activities of SCI model rats were
      tested by the 21-point Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined
      plane test and footprint analysis. In addition, Western blot analysis was
      performed to identify the expression of ER-stress related proteins including
      CHOP, GRP78 and caspase-12 both in vivo and in vitro. The level of cell apoptosis
      was determined by TUNEL in vivo and Flow cytometry in vitro. Relative downstream
      signals Akt/GSK-3beta and ERK1/2were also analyzed with or without inhibitors in
      vitro. RESULTS: Our results demonstrated that ER stress-induced apoptosis was
      involved in the injury of SCI model rats. NGF administration improved the motor
      function recovery and increased the neurons survival in the spinal cord lesions
      of the model rats. NGF decreases neuron apoptosis which measured by TUNEL and
      inhibits the activation of caspase-3 cascade. The ER stress-induced apoptosis
      response proteins CHOP, GRP78 and caspase-12 are inhibited by NGF treatment.
      Meanwhile, NGF administration also increased expression of growth-associated
      protein 43 (GAP43). The administration of NGF activated downstream signals
      Akt/GSK-3beta and ERK1/2 in ER stress cell model in vitro. CONCLUSION: The
      neuroprotective role of NGF in the recovery of SCI is related to the inhibition
      of ER stress-induced cell death via the activation of downstream signals, also
      suggested a new trend of NGF translational drug development in the central neural
      system injuries which involved in the regulation of chronic ER stress.

PMID- 24884852
TI  - Smoking, physical activity and healthy aging in India.
AB  - BACKGROUND: To identify levels of physical inactivity and smoking and examine
      their relationships to health among older people in India. METHODS: In 2010,
      Longitudinal Aging Study in India researchers interviewed 1,683 older adults in
      randomly sampled households with members aged >= 45 years in eight stratified
      districts in four states (90.9% response rate). We first used descriptive
      analyses to characterize older people in poor and good health. Differences
      between groups were established using chi-squared and t-tests. Multivariate
      logistic regression analyses were then performed to determine whether physical
      inactivity and smoking led to poor health while controlling for district of
      residence, caste, age, gender, marital status, and educational level. Regression
      analyses were also used to identify significant relationships between socio
      demographic characteristics and health behaviors. RESULTS: Larger proportions of
      older people in poor health were smokers (26.1% vs. 16.9%; p <= 0.001) and
      physically inactive (vigorous activities: 88.7% vs. 70.7%, p <= 0.001; moderate
      activities: 67.1% vs. 57.1%, p <= 0.01). Smoking (p <= 0.05) and lack of vigorous
      physical activity (p <= 0.001) increased the likelihood of poor health. Low
      educational level was significantly related to smoking and the lack of moderate
      physical activity (both p <= 0.001). Female gender decreased the likelihood of
      smoking. Male gender increased the likelihood of vigorous physical activity but
      decreased the likelihood of moderate physical activity. CONCLUSIONS: Smoking and
      physical inactivity have important impacts on the health of older people in
      India. Policy attention is needed to improve these modifiable health behaviors.

PMID- 24884853
TI  - Acid suppressive agents and risk of Mycobacterium tuberculosis: case-control
      study.
AB  - BACKGROUND: The acid-suppressive agents have been linked with an increased risk
      of infectious disease. The relationship between these drugs and Mycobacterium
      Tuberculosis (TB) was not been reported. METHODS: We conducted a case-control
      study using data from National Health Insurance research database of Taiwan. From
      1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9
      coding plus prescription two of four first-line anti-TB regimen for at least one
      month). Control subjects who were matched to the TB cases by age and sex were
      selected with 10:1 ratio. Medical records including acid-suppressive agent
      prescription and comorbidity, and socioeconomic status were analyzed. RESULTS: TB
      infection/activation was more frequent to comorbidity with chronic diseases,
      alcohol abuse, malignancy, immune deficient/suppression status and acid-related
      disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher
      exposure record to acid-suppressive agents within 3 months before TB index date
      (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and
      histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding
      factors, PPIs prescription 3 months before TB index date had an association of TB
      infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in
      H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive
      agents in TB infection/activation was fade gradually when the drug prescription
      period extended. CONCLUSIONS: Recent prescription of acid-suppressive agent seems
      to associate the TB infection/activation. In the society where TB was prevalent,
      evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.

PMID- 24884854
TI  - Evaluating team-based, lecture-based, and hybrid learning methods for neurology
      clerkship in China: a method-comparison study.
AB  - BACKGROUND: Neurology is complex, abstract, and difficult for students to learn.
      However, a good learning method for neurology clerkship training is required to
      help students quickly develop strong clinical thinking as well as problem-solving
      skills. Both the traditional lecture-based learning (LBL) and the relatively new
      team-based learning (TBL) methods have inherent strengths and weaknesses when
      applied to neurology clerkship education. However, the strengths of each method
      may complement the weaknesses of the other. Combining TBL with LBL may produce
      better learning outcomes than TBL or LBL alone. We propose a hybrid method (TBL +
      LBL) and designed an experiment to compare the learning outcomes with those of
      pure LBL and pure TBL. METHODS: One hundred twenty-seven fourth-year medical
      students attended a two-week neurology clerkship program organized by the
      Department of Neurology, Sun Yat-Sen Memorial Hospital. All of the students were
      from Grade 2007, Department of Clinical Medicine, Zhongshan School of Medicine,
      Sun Yat-Sen University. These students were assigned to one of three groups
      randomly: Group A (TBL + LBL, with 41 students), Group B (LBL, with 43 students),
      and Group C (TBL, with 43 students). The learning outcomes were evaluated by a
      questionnaire and two tests covering basic knowledge of neurology and clinical
      practice. RESULTS: The practice test scores of Group A were similar to those of
      Group B, but significantly higher than those of Group C. The theoretical test
      scores and the total scores of Group A were significantly higher than those of
      Groups B and C. In addition, 100% of the students in Group A were satisfied with
      the combination of TBL + LBL. CONCLUSIONS: Our results support our proposal that
      the combination of TBL + LBL is acceptable to students and produces better
      learning outcomes than either method alone in neurology clerkships. In addition,
      the proposed hybrid method may also be suited for other medical clerkships that
      require students to absorb a large amount of abstract and complex course
      materials in a short period, such as pediatrics and internal medicine clerkships.

PMID- 24884855
TI  - Recurring hyperammonemic encephalopathy induced by bacteria usually not producing
      urease.
AB  - BACKGROUND: Hyperammonemic encephalopathy may occur when urease-positive bacteria
      in the urinary tract produce ammonium which directly enters systemic circulation.
      Predisposing conditions such as a neurogenic bladder can increase both urinary
      tract infection and urine stagnation. CASE PRESENTATION: We describe the case of
      a 66 years old woman with a neurogenic bladder who twice developed hyperammonemic
      encephalopathy following urinary tract infection. During the second episode
      Escherichia coli and Enterococcus faecalis have been isolated in the urine. The
      neurologic examination showed psychomotor slowing, weak photomotor reflex,
      nystagmus in the lateral gaze and asterixis. The EEG showed triphasic waves which
      disappeared along with clinical recovery. CONCLUSION: Escherichia coli and
      Enterococcus faecalis are commonly considered urease-negative bacteria. Although
      frequently involved in urinary tract infections, their role in causing
      hyperammonemic encephalopathy have not been previously reported. Moreover,
      despite only one case with a neurogenic bladder have been described so far, our
      is the first patient with reoccurring hyperammonemic encephalopathy secondary to
      urinary tract infections.

PMID- 24884856
TI  - Fruiting bodies of the social amoeba Dictyostelium discoideum increase spore
      transport by Drosophila.
AB  - BACKGROUND: Many microbial phenotypes are the product of cooperative interactions
      among cells, but their putative fitness benefits are often not well understood.
      In the cellular slime mold Dictyostelium discoideum, unicellular amoebae
      aggregate when starved and form multicellular fruiting bodies in which stress
      resistant spores are held aloft by dead stalk cells. Fruiting bodies are thought
      to be adaptations for dispersing spores to new feeding sites, but this has not
      been directly tested. Here we experimentally test whether fruiting bodies
      increase the rate at which spores are acquired by passing invertebrates. RESULTS:
      Drosophila melanogaster accumulate spores on their surfaces more quickly when
      exposed to intact fruiting bodies than when exposed to fruiting bodies physically
      disrupted to dislodge spore masses from stalks. Flies also ingest and excrete
      spores that still express a red fluorescent protein marker. CONCLUSIONS:
      Multicellular fruiting bodies created by D. discoideum increase the likelihood
      that invertebrates acquire spores that can then be transported to new feeding
      sites. These results thus support the long-hypothesized dispersal benefits of
      altruism in a model system for microbial cooperation.

PMID- 24884857
TI  - Speculations on biting midges and other bloodsucking arthropods as alternative
      vectors of Leishmania.
AB  - Sand flies remain the only proven vectors of Leishmania spp. but recent
      implementation of PCR techniques has led to increasing speculation about
      "alternative vectors", including biting midges. Here, we summarize that PCR has
      considerable limits for studing the role of bloodsucking arthropods in the
      epidemiology of leishmaniasis. The Leishmania life cycle in the sand fly includes
      a complex series of interactions which are in many cases species-specific, the
      early phase of the infection is, however, non-specific to sand flies. These facts
      should be considered in detection of Leishmania in ,"alternative" or "new"
      vectors to avoid mistaken speculation about their vector competence. 

PMID- 24884858
TI  - A novel approach to minimizing adverse incentivization in healthcare payment
      systems.

PMID- 24884859
TI  - Toward a better understanding of patient-reported outcomes in clinical practice.
AB  - Current shifts toward patient-centered healthcare and accountable payment options
      point to the more personalized production of better health, not just healthcare,
      as a next organizational paradigm. Transformation to a system geared toward
      promoting health requires us to think broadly about what it means to engage
      patients meaningfully, to give them a voice in their health and care, and to
      capture more of their varied experience and attitudes beyond the provider visit.
      The collection and use of patient-reported outcome data into electronic health
      records represents an important step forward for the transition to a more patient
      centered health system. We set out an agenda for better understanding how and
      when patient-reported outcomes may improve patient health and care experience. 

PMID- 24884860
TI  - Consumer perspectives on personal health records: a 4-community study.
AB  - OBJECTIVES: To characterize consumer attitudes toward personal health records
      (PHRs) in 4 diverse communities across New York state (NYS). STUDY DESIGN:
      Combined analysis from four separate cross-sectional studies. METHODS: We
      analyzed pooled data from surveys separately administered to 4 NYS communities.
      Results from individual communities have been previously published. However,
      pooling the data allowed us to conduct multivariable regression analyses that
      identified key factors associated with potential usage among a broad group of
      consumers. RESULTS: We received responses from 701 consumers. A majority (74%) of
      respondents (n = 494) reported that they would use a PHR and the majority wanted
      a broad array of functionalities available. We found that potential PHR use was
      significantly associated with Internet use at least monthly (odds ratio [OR] =
      5.8, 95% confidence interval [CI] = 3.3-10.2), a belief that PHRs may improve the
      security of health information (OR = 2.6, 95% CI = 1.5-4.7), and a belief that
      PHRs may improve quality of care (OR = 4.1, 95% CI = 2.6-6.6). CONCLUSIONS: As
      federal initiatives aim to improve healthcare, which includes making care more
      patient centered, PHRs will likely play an increasing role. Our results provide
      critical information to inform policy efforts, suggesting that PHRs must offer a
      broad range of patient-centered functionalities while maintaining high privacy
      and security standards to narrow the gap between reported interest and actual
      use. Ensuring widespread access to and frequent use of the internet among
      consumers will also be critical to avoid creating healthcare disparities through
      PHR use.

PMID- 24884861
TI  - Physician behavior impact when revenue shifted from drugs to services.
AB  - OBJECTIVES: In partnership with a large nonprofit healthcare insurer for the Mid
      Atlantic region of the United States, we launched the first cancer clinical
      pathway in the United States in August 2008. Due to its early success with regard
      to savings and physician participation and compliance, a second-generation
      pathways program-the Oncology Medical Home-was piloted in 2011. This program
      offered a physician reimbursement model that shifted the source of revenue from
      drug reimbursement margin to professional charges for cognitive services
      (evaluation and management codes). We report our observations of the impact of
      that reimbursement model on physician prescribing behavior. STUDY DESIGN: This
      was a retrospective analysis. METHODS: A select group of practices that
      participated in the first-generation pathways program were invited to voluntarily
      participate in the Oncology Medical Home and its cognitive weighted reimbursement
      design. A matched control group was chosen from the first-generation pathways
      participants. Comparisons of physician behavior parameters were made pre- and
      postimplementation and between the Oncology Medical Home practices and the first
      generation pathways control group. RESULTS: Physician behavior was not
      significantly modified by cognitive weighted reimbursement. No significant change
      in frequency of office visits for established patients was observed. No change in
      chemotherapy prescribing was observed. Observed increases in generic regimen use
      were no different than matched control. CONCLUSIONS: Observations from this
      oncology medical home pilot program suggest that reimbursement methodology
      alternatives to the prevailing fee-for-service may have less impact on
      prescribing behavior than has been conjectured. Future research is ongoing to
      validate these observations and assess additional influences on prescribing
      behavior.

PMID- 24884862
TI  - Emergency department visit classification using the NYU algorithm.
AB  - OBJECTIVES: Reliable measures of emergency department (ED) use are important for
      studying ED utilization and access to care. We assessed the association of
      emergent classification of an ED visit based on the New York University ED
      Algorithm (EDA) with hospital mortality and hospital admission. STUDY DESIGN:
      Using diagnosis codes, we applied the EDA to classify ED visits into emergent,
      intermediate, and nonemergent categories and studied associations of emergent
      status with hospital mortality and hospital admissions. METHODS: We used a
      nationally representative sample of patients with visits to hospital-based EDs
      from repeated cross sections of the National Hospital Ambulatory Medical Care
      Survey from 2006 to 2009. We performed survey-weighted logistic regression
      analyses, adjusting for year and patient demographic and socioeconomic
      characteristics, to estimate the association of emergent ED visits with the
      probability of hospital mortality or hospital admission. RESULTS: The EDA measure
      of emergent visits was significantly and positively associated with mortality
      (odds ratio [OR]: 3.79, 95% confidence interval [CI]: 2.50-5.75) and hospital
      admission (OR: 5.28, 95% CI, 4.93-5.66). CONCLUSIONS: This analysis assessed the
      NYU algorithm in measuring emergent and nonemergent ED use in the general
      population. Emergent classification based on the algorithm was strongly and
      significantly positively associated with hospitalization and death in a
      nationally representative population. The algorithm can be useful in studying ED
      utilization and evaluating policies that aim to change it.

PMID- 24884863
TI  - How does drug coverage vary by insurance type? Analysis of argue formularies in
      the United States.
AB  - OBJECTIVES: To quantify how access to on-patent drugs by tier placement varies by
      insurance type and therapeutic area. STUDY DESIGN: Retrospective analysis of
      insurance plan drug coverage data. METHODS: Drug coverage information was
      collected from the Fingertip Formulary database in May 2011 for 3 drug classes
      (statins, angiotensin II receptor blockers, and protein-tyrosine kinase
      inhibitors) across 3 therapeutic areas with varying levels of generic drug
      availability. A generalized linear model was used to estimate the percentage of
      available on-patent drugs covered in the formulary tiers with lowest copay
      requirements (tiers 1 and 2) in different types of healthcare insurance plans in
      the United States. RESULTS: There were substantial differences between insurance
      types in the number of on-patent drugs reimbursed in tiers 1 and 2 (ie, with a
      low copay). Compared with commercial plans, there were more on-patent drugs
      reimbursed with a low copay in employer plans, union plans, and with pharmacy
      benefit management companies, and substantially fewer on-patent drugs with a low
      copay in Medicare plans (Medicare Advantage, special needs, prescription drug
      plans) and discount prescription programs. These results were expected, as union
      plans are known for their generosity and Medicare plans rely heavily on cost
      containment (eg, cost sharing). For commercial Medicaid and municipal plans, the
      findings were dependent on the therapeutic class, or were inconclusive. The
      number of competitors a plan faces did not consistently affect the coverage of on
      patent drugs. CONCLUSIONS: The degree of coverage of on-patent drugs in the
      lowest copay tiers varies dramatically between insurance types, especially for
      expensive protein-tyrosine kinase inhibitors.

PMID- 24884865
TI  - A simple method for the prediction of the detonation performances of metal
      containing explosives.
AB  - Accurate prediction to the detonation performances of different kinds of
      energetic materials has attracted significant attention in the area of high
      energy density materials (HEDMs). A common approach for the estimation of CHNO
      explosives is the Kamlet-Jacobs (K-J) equation. However, with the development of
      energetic materials, the components of explosives are no longer restricted to
      CHNO elements. In this study, we have extended the K-J equation to the
      calculation of certain metal-containing explosives. A new empirical method, in
      which metal elements are assumed to form metallic oxides, has been developed on
      the basis of the largest exothermic principle. In this method, metal oxides can
      be deemed as inert solids that release heat other than gases. To evaluate the
      prediction accuracy of new method, a commercial program EXPLO5 has been employed
      for the calculation. The difference involved in the ways of treating products has
      been taken into account, and the detonation parameters from two methods were
      subject to close comparison. The results suggest that the mean absolute values
      (MAVs) of relative deviation for detonation velocity (D) and detonation pressure
      (P) are less than 5%. Overall, this new method has exhibited excellent accuracy
      and simplicity, affording an efficient way to estimate the performance of
      explosives without relying on sophisticated computer programs. Therefore, it will
      be helpful in designing and synthesizing new metallic energetic compounds. 

PMID- 24884864
TI  - Having mentors and campus social networks moderates the impact of worries and
      video gaming on depressive symptoms: a moderated mediation analysis.
AB  - BACKGROUND: Easy access to the internet has spawned a wealth of research to
      investigate the effects of its use on depression. However, one limitation of many
      previous studies is that they disregard the interactive mechanisms of risk and
      protective factors. The aim of the present study was to investigate a resilience
      model in the relationship between worry, daily internet video game playing, daily
      sleep duration, mentors, social networks and depression, using a moderated
      mediation analysis. METHODS: 6068 Korean undergraduate and graduate students
      participated in this study. The participants completed a web-based mental health
      screening questionnaire including the Beck Depression Inventory (BDI) and
      information about number of worries, number of mentors, number of campus social
      networks, daily sleep duration, daily amount of internet video game playing and
      daily amount of internet searching on computer or smartphone. A moderated
      mediation analysis was carried out using the PROCESS macro which allowed the
      inclusion of mediators and moderator in the same model. RESULTS: The results
      showed that the daily amount of internet video game playing and daily sleep
      duration partially mediated the association between the number of worries and the
      severity of depression. In addition, the mediating effect of the daily amount of
      internet video game playing was moderated by both the number of mentors and the
      number of campus social networks. CONCLUSIONS: The current findings indicate that
      the negative impact of worry on depression through internet video game playing
      can be buffered when students seek to have a number of mentors and campus social
      networks. Interventions should therefore target individuals who have higher
      number of worries but seek only a few mentors or campus social networks. Social
      support via campus mentorship and social networks ameliorate the severity of
      depression in university students.

PMID- 24884866
TI  - The gut microbiota of larvae of Rhynchophorus ferrugineus Oliver (Coleoptera:
      Curculionidae).
AB  - BACKGROUND: The red palm weevil (RPW) Rhynchophorus ferrugineus Olivier
      (Coleoptera: Curculionidae) is one of the major pests of palms. The larvae bore
      into the palm trunk and feed on the palm tender tissues and sap, leading the host
      tree to death. The gut microbiota of insects plays a remarkable role in the host
      life and understanding the relationship dynamics between insects and their
      microbiota may improve the biological control of insect pests. The purpose of
      this study was to analyse the diversity of the gut microbiota of field-caught RPW
      larvae sampled in Sicily (Italy). RESULTS: The 16S rRNA gene-based Temporal
      Thermal Gradient Gel Electrophoresis (TTGE) of the gut microbiota of RPW field
      trapped larvae revealed low bacterial diversity and stability of the community
      over seasons and among pools of larvae from different host trees. Pyrosequencing
      of the 16S rRNA gene V3 region confirmed low complexity and assigned 98% of the
      75,564 reads to only three phyla: Proteobacteria (64.7%) Bacteroidetes (23.6%)
      and Firmicutes (9.6%) and three main families [Enterobacteriaceae (61.5%),
      Porphyromonadaceae (22.1%) and Streptococcaceae (8.9%)]. More than half of the
      reads could be classified at the genus level and eight bacterial genera were
      detected in the larval RPW gut at an abundance >=1%: Dysgonomonas (21.8%),
      Lactococcus (8.9%), Salmonella (6.8%), Enterobacter (3.8%), Budvicia (2.8%),
      Entomoplasma (1.4%), Bacteroides (1.3%) and Comamonas (1%). High abundance of
      Enterobacteriaceae was also detected by culturing under aerobic conditions.
      Unexpectedly, acetic acid bacteria (AAB), that are known to establish symbiotic
      associations with insects relying on sugar-based diets, were not detected.
      CONCLUSIONS: The RPW gut microbiota is composed mainly of facultative and
      obligate anaerobic bacteria with a fermentative metabolism. These bacteria are
      supposedly responsible for palm tissue fermentation in the tunnels where RPW
      larvae thrive and might have a key role in the insect nutrition, and other
      functions that need to be investigated.

PMID- 24884867
TI  - Perioperative blood transfusion adversely affects prognosis after resection of
      lung cancer: a systematic review and a meta-analysis.
AB  - BACKGROUND: It is speculated that blood transfusion may induce adverse
      consequences after cancer surgery due to immunosuppression. This study was
      intended to assess the impact of perioperative blood transfusion on the prognosis
      of patients who underwent lung cancer resection. METHODS: Eligible studies were
      identified through a computerized literature search. The pooled relative risk
      ratio (RR) with 95% confidence interval (CI) was calculated using Review Manager
      5.1 Software. RESULTS: Eighteen studies with a total of 5915 participants were
      included for this meta-analysis. Pooled analysis showed that perioperative blood
      transfusion was associated with worse overall survival (RR: 1.25, 95% CI: 1.13
      1.38; P <0.001) and recurrence-free survival (RR: 1.42, 95% CI: 1.20-1.67; P
      <0.001) in patients with resected lung cancer. CONCLUSIONS: Perioperative blood
      transfusion appears be associated with a worse prognosis in patients undergoing
      lung cancer resection. These data highlight the importance of minimizing blood
      transfusion during surgery.

PMID- 24884868
TI  - Early results of urethral dose reduction and small safety margin in intensity
      modulated radiation therapy (IMRT) for localized prostate cancer using a real
      time tumor-tracking radiotherapy (RTRT) system.
AB  - BACKGROUND: We prospectively assessed the utility of intensity-modulated
      radiation therapy (IMRT) with urethral dose reduction and a small margin between
      the clinical target volume (CTV) and the planning target volume (PTV) for
      patients with localized prostate cancer. METHODS: The study population was 110
      patients in low- (14.5%), intermediate- (41.8%), and high-risk (43.6%)
      categories. Three gold fiducial markers were inserted into the prostate. A soft
      guide-wire was used to identify the urethra when computed tomography (CT) scan
      for treatment planning was performed. A dose constraint of V70 < 10% was applied
      to the urethral region. Margins between the CTV-PTV were set at 3 mm in all
      directions. Patients were treated with 70 Gy IMRT in 30 fractions (D95 of PTV)
      over 7.5 weeks. The patient couch was adjusted to keep the gold markers within
      2.0 mm from their planned positions with the use of frequent on-line
      verification. RESULTS: The median follow-up period was 31.3 (3.2 to 82.1) months.
      The biochemical relapse-free survival (bRFS) rates at 3 years were 100%, 93.8%
      and 89.5% for the low-, intermediate-, and high-risk patients, respectively. The
      incidences of acute adverse events (AEs) were 45.5% and 0.9% for grades 1 and 2,
      respectively. The late AEs were grade 1 cystitis in 10.0% of the patients, rectal
      bleeding in 7.3%, and urinary urgency in 6.4%. Only three patients (2.7%)
      developed grade 2 late AEs. CONCLUSIONS: On-line image guidance with precise
      correction of the table position during radiotherapy achieved one of the lowest
      AEs rates with a bRFS equal to the highest in the literature.

PMID- 24884870
TI  - Smear positive pulmonary tuberculosis and its risk factors among tuberculosis
      suspect in South East Ethiopia; a hospital based cross-sectional study.
AB  - BACKGROUND: Tuberculosis remains a deadly infectious disease, affecting millions
      of people worldwide. Ethiopia ranks seventh among the twenty two high
      tuberculosis burden countries. The aim of this study was to determine the
      prevalence of smear positive pulmonary tuberculosis and its associated risk
      factors in Goba and Robe hospitals of Bale zone. METHODS: A cross-sectional study
      was conducted on tuberculosis suspected patients from February-May 2012. Sputum
      samples were examined for acid fast bacilli using Ziehl-Neelsen staining and
      interview was conducted for each patient. Descriptive statistics, binary logistic
      and multivariable logistic regression analyses were employed to identify factors
      associated with pulmonary tuberculosis infection. RESULT: The prevalence of smear
      positive tuberculosis was 9.2%. Age >36 (AOR = 3.54, 95% CI = 1. 3-9.82), marital
      status (AOR = 8.40, 95% CI = 3.02-23.20), family size (AOR = 4. 10, 95% CI = 1.60
      10.80), contact with active tuberculosis patient (AOR = 5. 90; 95% CI = 2. 30
      15.30), smoking cigarette regularly (AOR = 3. 90; 95% CI = 1. 20-12.40), and
      human immunodeficiency virus sero-status (AOR = 11. 70; 95% CI = 4. 30-31.70)
      were significantly associated with smear positive pulmonary tuberculosis.
      CONCLUSION: The prevalence of smear positive pulmonary tuberculosis was high in
      the study area. Age, marital status, family size, history of contact with active
      tuberculosis patient, smoking cigarettes, and HIV sero-status were among the risk
      factors significantly associated with acquiring tuberculosis. Hence, strict
      pulmonary tuberculosis screening of HIV patients and intensification of health
      education to avoid risk factors identified are recommended.

PMID- 24884869
TI  - A rice calcium-dependent protein kinase OsCPK9 positively regulates drought
      stress tolerance and spikelet fertility.
AB  - BACKGROUND: In plants, calcium-dependent protein kinases (CDPKs) are involved in
      tolerance to abiotic stresses and in plant seed development. However, the
      functions of only a few rice CDPKs have been clarified. At present, it is unclear
      whether CDPKs also play a role in regulating spikelet fertility. RESULTS: We
      cloned and characterized the rice CDPK gene, OsCPK9. OsCPK9 transcription was
      induced by abscisic acid (ABA), PEG6000, and NaCl treatments. The results of
      OsCPK9 overexpression (OsCPK9-OX) and OsCPK9 RNA interference (OsCPK9-RNAi)
      analyses revealed that OsCPK9 plays a positive role in drought stress tolerance
      and spikelet fertility. Physiological analyses revealed that OsCPK9 improves
      drought stress tolerance by enhancing stomatal closure and by improving the
      osmotic adjustment ability of the plant. It also improves pollen viability,
      thereby increasing spikelet fertility. In OsCPK9-OX plants, shoot and root
      elongation showed enhanced sensitivity to ABA, compared with that of wild-type.
      Overexpression and RNA interference of OsCPK9 affected the transcript levels of
      ABA- and stress-responsive genes. CONCLUSIONS: Our results demonstrated that
      OsCPK9 is a positive regulator of abiotic stress tolerance, spikelet fertility,
      and ABA sensitivity.

PMID- 24884872
TI  - Photothermally targeted thermosensitive polymer-masked nanoparticles.
AB  - The targeted delivery of therapeutic cargos using noninvasive stimuli has the
      potential to improve efficacy and reduce off-target effects (toxicity). Here, we
      demonstrate a targeting mechanism that uses a thermoresponsive copolymer to mask
      a peptide ligand that binds a widely distributed receptor (integrin beta1) on the
      surface of silica core-gold shell nanoparticles. The nanoparticles convert NIR
      light into heat, which causes the copolymer to collapse, exposing the ligand
      peptide, allowing cell binding. The use of NIR light could allow targeting of
      plasmonic nanoparticles deep within tissues. This approach could be extended to a
      variety of applications including photothermal therapy and drug delivery. 

PMID- 24884871
TI  - Serum cytokine biomarker panels for discriminating pancreatic cancer from benign
      pancreatic disease.
AB  - BACKGROUND: We investigated whether combinations of serum cytokines, used with
      logistic disease predictor models, could facilitate the detection of pancreatic
      ductal adenocarcinoma (PDAC). METHODS: The serum levels of 27 cytokines were
      measured in 241 subjects, 127 with PDAC, 49 with chronic pancreatitis, 20 with
      benign biliary obstruction and 45 healthy controls. Samples were split randomly
      into independent training and test sets. Cytokine biomarker panels were selected
      by identifying the top performing cytokines in best fit logistic regression
      models during multiple rounds of resampling from the training dataset. Disease
      prediction by logistic models, built using the resulting cytokine panels, was
      evaluated with training and test sets and further examined using resampled
      performance evaluation. RESULTS: For the discrimination of PDAC patients from
      patients with benign disease, a panel of IP-10, IL-6, PDGF plus CA19-9 offered
      improved diagnostic performance over CA19-9 alone in the training (AUC 0.838 vs.
      0.678) and independent test set (AUC 0.884 vs. 0.798). For the discrimination of
      PDAC from CP, a panel of IL-8, CA19-9, IL-6 and IP-10 offered improved diagnostic
      performance over CA19-9 alone with the training (AUC 0.880 vs. 0.758) and test
      set (AUC 0.912 vs. 0.848). Finally, for the discrimination of PDAC in the
      presence of jaundice from benign controls with jaundice, a panel of IP-10, IL-8,
      IL-1b and PDGF demonstrated improvement over CA19-9 in the training (AUC 0.810
      vs. 0.614) and test set (AUC 0.857 vs. 0.659). CONCLUSIONS: These findings
      support the potential role for cytokine panels in the discrimination of PDAC from
      patients with benign pancreatic diseases and warrant additional study.

PMID- 24884873
TI  - Enhancement of femtosecond lenticule extraction for visual symptomatic eye after
      myopia correction.
AB  - BACKGROUND: The novel Femtosecond lenticule extraction (FLEx) procedure has been
      considered safe, predictable, and effective in treating myopia and myopic
      astigmatism, with few complications. However, an enhancement procedure after FLEx
      may be required in some cases, but has not been reported in detail. CASE
      PRESENTATION: A 24-year-old woman who had undergone bilateral FLEx with the
      VisuMax femtosecond laser treatment for myopic astigmatism complained of double
      vision in her left eye after the operation. The manifest refraction was -0.50/
      1.25 * 180 degrees . The corneal topography showed a central-inferior steepened
      zone. The ocular wavefront measurements displayed a high value of total
      aberrations as well as coma. She was scheduled for an enhancement procedure and
      it was performed by relifting the primary FLEx flap in the left eye four months
      later. Ablation was made with the Mel-80 excimer laser. After retreatment, the
      corresponding aberrations were diminished and the corneal topography turned
      flattened. Her symptom resolved completely with good visual outcomes. CONCLUSION:
      This first detailed case report demonstrates the feasibility and efficacy of
      enhancement after FLEx for visual symptomatic eye after myopia correction. An
      analysis of more cases would be necessary to determine a more definite profile.

PMID- 24884874
TI  - Indirect genetic effects contribute substantially to heritable variation in
      aggression-related traits in group-housed mink (Neovison vison).
AB  - BACKGROUND: Since the recommendations on group housing of mink (Neovison vison)
      were adopted by the Council of Europe in 1999, it has become common in mink
      production in Europe. Group housing is advantageous from a production
      perspective, but can lead to aggression between animals and thus raises a welfare
      issue. Bite marks on the animals are an indicator of this aggressive behaviour
      and thus selection against frequency of bite marks should reduce aggression and
      improve animal welfare. Bite marks on one individual reflect the aggression of
      its group members, which means that the number of bite marks carried by one
      individual depends on the behaviour of other individuals and that it may have a
      genetic basis. Thus, for a successful breeding strategy it could be crucial to
      consider both direct (DGE) and indirect (IGE) genetic effects on this trait.
      However, to date no study has investigated the genetic basis of bite marks in
      mink. RESULT AND DISCUSSION: A model that included DGE and IGE fitted the data
      significantly better than a model with DGE only, and IGE contributed a
      substantial proportion of the heritable variation available for response to
      selection. In the model with IGE, the total heritable variation expressed as the
      proportion of phenotypic variance (T2) was six times greater than classical
      heritability (h2). For instance, for total bite marks, T2 was equal to 0.61,
      while h2 was equal to 0.10. The genetic correlation between direct and indirect
      effects ranged from 0.55 for neck bite marks to 0.99 for tail bite marks. This
      positive correlation suggests that mink have a tendency to fight in a reciprocal
      way (giving and receiving bites) and thus, a genotype that confers a tendency to
      bite other individuals can also cause its bearer to receive more bites.
      CONCLUSION: Both direct and indirect genetic effects contribute to variation in
      number of bite marks in group-housed mink. Thus, a genetic selection design that
      includes both direct genetic and indirect genetic effects could reduce the
      frequency of bite marks and probably aggression behaviour in group-housed mink.

PMID- 24884875
TI  - Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show
      ALDH(high)CD44(+) phenotype and sphere-forming capacity.
AB  - BACKGROUND: Conventional chemotherapy in malignant pleural mesothelioma (MPM) has
      minimal impact on patient survival due to the supposed chemoresistance of cancer
      stem cells (CSCs). We sought to identify a sub-population of chemoresistant cells
      by using putative CSC markers, aldehyde dehydrogenase (ALDH) and CD44 in three
      MPM cell lines; H28, H2052 and Meso4. METHODS: The Aldefluor assay was used to
      measure ALDH activity and sort ALDH(high) and ALDH(low) cells. Drug-resistance
      was evaluated by cell viability, anchorage-independent sphere formation, flow
      cytometry and qRT-PCR analyses. RESULTS: The ALDH(high) - and ALDH(low) -sorted
      fractions were able to demonstrate phenotypic heterogeneity and generate spheres,
      the latter being less efficient, and both showed an association with CD44. Cis-
      diamminedichloroplatinum (II) (cisplatin) treatment failed to reduce ALDH
      activity and conferred only a short-term inhibition of sphere generation in both
      ALDH(high) and ALDH(low) fractions of the three MPM cell lines. Induction of drug
      sensitivity by an ALDH inhibitor, diethylaminobenzaldehyde (DEAB) resulted in
      significant reductions in cell viability but not a complete elimination of the
      sphere-forming cells, suggestive of the presence of a drug-resistant
      subpopulation. At the transcript level, the cisplatin + DEAB-resistant cells
      showed upregulated mRNA expression levels for ALDH1A2, ALDH1A3 isozymes and CD44
      indicating the involvement of these markers in conferring chemoresistance in both
      ALDH(high) and ALDH(low) fractions of the three MPM cell lines. CONCLUSIONS: Our
      study shows that ALDH(high) CD44(+) cells are implicated in conveying tolerance
      to cisplatin in the three MPM cell lines. The combined use of CD44 and ALDH
      widens the window for identification and targeting of a drug-resistant population
      which may improve the current treatment modalities in mesothelioma.

PMID- 24884876
TI  - Identification of G protein-coupled receptors in Schistosoma haematobium and S.
      mansoni by comparative genomics.
AB  - BACKGROUND: Schistosomiasis is a parasitic disease affecting ~200 million people
      worldwide. Schistosoma haematobium and S. mansoni are two relatively closely
      related schistosomes (blood flukes), and the causative agents of urogenital and
      hepatointestinal schistosomiasis, respectively. The availability of genomic,
      transcriptomic and proteomic data sets for these two schistosomes now provides
      unprecedented opportunities to explore their biology, host interactions and
      schistosomiasis at the molecular level. A particularly important group of
      molecules involved in a range of biological and developmental processes in
      schistosomes and other parasites are the G protein-coupled receptors (GPCRs).
      Although GPCRs have been studied in schistosomes, there has been no detailed
      comparison of these receptors between closely related species. Here, using a
      genomic-bioinformatic approach, we identified and characterised key GPCRs in S.
      haematobium and S. mansoni (two closely related species of schistosome). METHODS:
      Using a Hidden Markov Model (HMM) and Support Vector Machine (SVM)-based
      pipeline, we classified and sub-classified GPCRs of S. haematobium and S.
      mansoni, combined with phylogenetic and transcription analyses. RESULTS: We
      identified and classified classes A, B, C and F as well as an unclassified group
      of GPCRs encoded in the genomes of S. haematobium and S. mansoni. In addition, we
      characterised ligand-specific subclasses (i.e. amine, peptide, opsin and orphan)
      within class A (rhodopsin-like). CONCLUSIONS: Most GPCRs shared a high degree of
      similarity and conservation, except for members of a particular clade (designated
      SmGPR), which appear to have diverged between S. haematobium and S. mansoni and
      might explain, to some extent, some of the underlying biological differences
      between these two schistosomes. The present set of annotated GPCRs provides a
      basis for future functional genomic studies of cellular GPCR-mediated signal
      transduction and a resource for future drug discovery efforts in schistosomes.

PMID- 24884877
TI  - Clinician-led improvement in cancer care (CLICC)--testing a multifaceted
      implementation strategy to increase evidence-based prostate cancer care: phased
      randomised controlled trial--study protocol.
AB  - BACKGROUND: Clinical practice guidelines have been widely developed and
      disseminated with the aim of improving healthcare processes and patient outcomes
      but the uptake of evidence-based practice remains haphazard. There is a need to
      develop effective implementation methods to achieve large-scale adoption of
      proven innovations and recommended care. Clinical networks are increasingly being
      viewed as a vehicle through which evidence-based care can be embedded into
      healthcare systems using a collegial approach to agree on and implement a range
      of strategies within hospitals. In Australia, the provision of evidence-based
      care for men with prostate cancer has been identified as a high priority.
      Clinical audits have shown that fewer than 10% of patients in New South Wales
      (NSW) Australia at high risk of recurrence after radical prostatectomy receive
      guideline recommended radiation treatment following surgery. This trial will test
      a clinical network-based intervention to improve uptake of guideline recommended
      care for men with high-risk prostate cancer. METHODS/DESIGN: In Phase I, a phased
      randomised cluster trial will test a multifaceted intervention that harnesses the
      NSW Agency for Clinical Innovation (ACI) Urology Clinical Network to increase
      evidence-based care for men with high-risk prostate cancer following surgery. The
      intervention will be introduced in nine NSW hospitals over 10 months using a
      stepped wedge design. Outcome data (referral to radiation oncology for discussion
      of adjuvant radiotherapy in line with guideline recommended care or referral to a
      clinical trial of adjuvant versus salvage radiotherapy) will be collected through
      review of patient medical records. In Phase II, mixed methods will be used to
      identify mechanisms of provider and organisational change. Clinicians' knowledge
      and attitudes will be assessed through surveys. Process outcome measures will be
      assessed through document review. Semi-structured interviews will be conducted to
      elucidate mechanisms of change. DISCUSSION: The study will be one of the first
      randomised controlled trials to test the effectiveness of clinical networks to
      lead changes in clinical practice in hospitals treating patients with high-risk
      cancer. It will additionally provide direction regarding implementation
      strategies that can be effectively employed to encourage widespread adoption of
      clinical practice guidelines. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry (ANZCTR): ACTRN12611001251910.

PMID- 24884879
TI  - A qualitative study of contextual factors' impact on measures to reduce surgery
      cancellations.
AB  - BACKGROUND: Contextual factors influence quality improvement outcomes.
      Understanding this influence is important when adapting and implementing
      interventions and translating improvements into new settings. To date, there is
      limited knowledge about how contextual factors influence quality improvement
      processes. In this study, we explore how contextual factors affected measures to
      reduce surgery cancellations, which are a persistent problem in healthcare. We
      discuss the usefulness of the theoretical framework provided by the model for
      understanding success in quality (MUSIQ) for this kind of research. METHOD: We
      performed a qualitative case study at Forde Hospital, Norway, where we had
      previously demonstrated a reduction in surgery cancellations. We interviewed 20
      clinicians and performed content analysis to explore how contextual factors
      affected measures to reduce cancellations of planned surgeries. RESULTS: We
      identified three common themes concerning how contextual factors influenced the
      change process: 1) identifying a need to change, 2) facilitating system-wide
      improvement, and 3) leader involvement and support. Input from patients helped
      identify a need to change and contributed to the consensus that change was
      necessary. Reducing cancellations required improving the clinical system. This
      improvement process was based on a strategy that emphasized the involvement of
      frontline clinicians in detecting and improving system problems. Clinicians
      shared information about their work by participating in improvement teams to
      develop a more complete understanding of the clinical system and its
      interdependencies. This new understanding allowed clinicians to detect system
      problems and design adequate interventions. Middle managers' participation in the
      improvement teams and in regular work processes was important for successfully
      implementing and adapting interventions. CONCLUSION: Contextual factors
      interacted with one another and with the interventions to facilitate changes in
      the clinical system, reducing surgery cancellations. The MUSIQ framework is
      useful for exploring how contextual factors influence the improvement process and
      how they influence one another. Discussing data in relation to a theoretical
      framework can promote greater uniformity in reporting findings, facilitating
      knowledge-building across studies.

PMID- 24884878
TI  - Subjective health complaints in patients with lumbar radicular pain and disc
      herniation are associated with a sex - OPRM1 A118G polymorphism interaction: a
      prospective 1-year observational study.
AB  - BACKGROUND: Earlier observations show that development of persistent pain may be
      associated with the genetic variability in the gene encoding for the MU-opioid
      receptor 1, the OPRM1 A118G (rs1799971). The aim of this study was to investigate
      the association between OPRM1 genotype and subjective health complaints in
      patients with radicular pain and disc herniation. METHODS: A prospective, 1-year
      observational study was conducted at a hospital back clinic, including 118
      Caucasian patients with lumbar radicular pain and MRI confirmed disc herniation.
      Single nucleotide polymorphism genotyping regarding the OPRM1 A118G was
      performed. The data of individuals with AA versus AG or GG were analysed
      separately by linear mixed models. The Subjective Health Complaints Inventory (0
      81) including 27 common complaints experienced the previous month on a scale from
      not at all (0) to severe (3) was used as outcome. Pain, prior duration of leg
      pain, age, smoking status, and lumbar disc surgery were considered as covariates.
      RESULTS: In total 23 of 118 patients were carriers of the OPRM1 G-allele. All
      patients except female carriers of the G-allele reported a decrease in pain from
      baseline to 1 year. Female carriers of the G-allele reported significantly higher
      subjective health complaints score during the study time span than male carriers
      of the G-allele when controlling for pain and pain duration. CONCLUSION: The
      present data indicate that, when controlling for pain intensity and duration,
      subjective health complaints are associated with a sex - OPRM1 A118G polymorphism
      interaction in patients with radicular pain.

PMID- 24884880
TI  - Inferior oncological prognosis of surgery without oral chemotherapy for stage III
      colon cancer in clinical settings.
AB  - BACKGROUND: Cancer patients not admissible for adjuvant chemotherapy are
      generally at high risk of considerably inferior prognosis. The aim of this
      retrospective study was to evaluate poorer survival without administration of
      oral adjuvant chemotherapy of stage III colon cancer patients in clinical
      settings. METHODS: Between April 2007 and September 2011, 259 patients with stage
      III colon cancer who underwent curative surgery were retrospectively assigned to
      the adjuvant chemotherapy group of 171 patients (66%) and the surgery alone group
      of 88 patients. Oral fluorouracil (5-FU) derivatives used in adjuvant
      chemotherapy, such as oral uracil and tegafur plus leucovorin (UFT/LV) or
      capecitabine, were the most commonly used. RESULTS: The 3-year relapse-free
      survival (RFS) rates were 74.9% for all cases, 58.3% for the surgery alone group,
      and 83.4% for the adjuvant chemotherapy group (P=0.0001). The chemotherapy group
      was associated with a dramatic improvement in survival for stage IIIB (surgery
      alone 57.7% versus adjuvant chemotherapy 83.9%; P=0.0001) and stage IIIC (surgery
      alone 18.2% versus adjuvant chemotherapy 57.3%; P=0.006) patients. There was a
      significant difference in the overall recurrence rate between groups (surgery
      alone 35.2% versus adjuvant chemotherapy 18.1%; P=0.002). Multivariate analysis
      identified adjuvant therapy as an independent predictive factor of reduced
      recurrence (hazard ratio (HR): 3.231; P=0.004) and improved RFS (HR: 2.653;
      P=0.001). CONCLUSION: In clinical settings, adjuvant therapy was the only
      significant prognostic factor of survival. Since many patients prefer not to
      receive chemotherapy, it is critical to inform stage III colon cancer patients
      that chemotherapy raises their chances of survival by three-fold compared with
      curative surgery alone.

PMID- 24884881
TI  - In vivo effect of two first-line ART regimens on inflammatory mediators in male
      HIV patients.
AB  - BACKGROUND: Persistent immune activation and inflammation are lying behind HIV
      infection even in the setting of ART mediated viral suppression. The purpose of
      this study is to define the in vivo effect of two first-line ART regimens on
      certain inflammatory mediators in male HIV patients. METHODS: Male, naive, HIV
      infected volunteers were assigned either to tenofovir-DF/emtricitabine/efavirenz
      (Group_T) or abacavir/lamivudine/efavirenz (Group_A). Platelet Activating Factor
      (PAF) levels and metabolic enzymes together with HIV-implicated cytokines (IL
      1beta, IL-6, IL-8, IL-10, IL-12p70, TNFa) and VEGF were determined for a 12-month
      period. Differences within each group were determined by non-parametric Friedman
      and Wilcoxon test, while the differences between the groups were checked by ANOVA
      repeated measures. RESULTS: Both ART regimens present pronounced effect on
      inflammatory mediators, resulting in decreased PAF levels and Lipoprotein
      associated phospholipase A2 (Lp-PLA2) activity for tenofovir-containing regimen
      and same as baseline PAF levels with a peak though at the 3rd month as well as
      elevated Lp-PLA2 activity for abacavir-containing regimen. CONCLUSIONS: Studies
      regarding the effect of first-line ART regimens on inflammation may be beneficial
      in preventing chronic morbidities during HIV-treatment. From this point of view,
      the present study suggests an anti-inflammatory effect of tenofovir-containing
      ART, while the temporary increase of PAF levels in abacavir-containing ART may be
      the link between the reported cardiovascular risk and abacavir administration.

PMID- 24884882
TI  - Glomerular changes and alterations of zonula occludens-1 in the kidneys of
      Plasmodium falciparum malaria patients.
AB  - BACKGROUND: The process of cytoadhesion in Plasmodium falciparum malaria
      infection causes signaling processes that lead to structural and functional
      changes at the cellular level. Histopathological changes of acute kidney injury
      (AKI) in P. falciparum malaria often involve glomerular proliferation, thickening
      of the glomerular basement membrane, acute tubular necrosis, and interstitial
      inflammation. Focusing on the glomeruli, this study aimed to investigate
      glomerular and tight junction-associated protein- zonula occludens-1 (ZO-1)
      changes in P. falciparum malaria patients. METHODS: Kidney tissues were grouped
      into P. falciparum with AKI (Cr >= 265 MUmol/L or 3 mg/dl), P. falciparum without
      AKI (Cr < 265 MUmol/L), and normal kidney tissues (control group). Glomerular
      cells and the glomerular area were quantified and compared in three experimental
      groups. The tight junction was investigated immunohistochemically using tight
      junction-associated protein, ZO-1, protein marker. A further immunofluorescence
      study was performed in an endothelial cell (EC)-parasitized red blood cell (PRBC)
      co-culture system, to evaluate the tight junction protein. RESULTS: Glomerular
      cell proliferation was significant in P. falciparum with AKI (Cr >= 265 MUmol/L).
      By contrast, the glomerular area decreased significantly. ZO-1 expression was
      significantly decreased in the AKI group compared with normal kidneys, and in
      kidney tissues without AKI (p < 0.05). This was further confirmed by the
      depletion in ZO-1 localization in ECs co-cultured with PRBCs. CONCLUSIONS: In P.
      falciparum malaria with AKI, the decrease in glomerular area, despite glomerular
      cell proliferation, could be due to the collapse of cellular structures secondary
      to damaged tight junction-associated protein, ZO-1.

PMID- 24884883
TI  - Receptionist rECognition and rEferral of PaTients with Stroke (RECEPTS) study -
      protocol of a mixed methods study.
AB  - BACKGROUND: As the first point of contact for patients and witnesses of stroke,
      General Practice receptionists can be instrumental in deciding the urgency of
      clinical contact. Despite the considerable complexity of this task, reception
      staff are not clinically trained. Minimising the time taken to access
      thrombolysis is crucial in acute stroke as treatment must be initiated within 4.5
      hours of the onset, and the earlier the better, to achieve the best outcomes.
      Research suggests that patients who first contact their General Practice
      following the onset of stroke symptoms are less likely to receive thrombolysis,
      in part due to significant delays within Primary Care.This study therefore aims
      to understand the role of General Practice receptionists, with particular
      interest in receptionist's ability to recognise people who may be suffering from
      a stroke and to handle such patients as a medical emergency. METHODS: The
      Receptionist rECognition and rEferral of PaTients with Stroke (RECEPTS) study
      will be a Primary Care based mixed methods study. 60 General Practices in the
      West Midlands will be recruited. Each practice will receive 10 unannounced
      simulated patient telephone calls, after the 10 calls questionnaires will be
      administered to each receptionist. These will examine the behaviour of
      receptionists towards patients presenting in Primary Care with stroke symptoms,
      and their knowledge of stroke symptoms. An embedded qualitative study will use
      interviews and focus groups to investigate the views of General Practice staff on
      the receptionists' role in patient referral and whether training in this area
      would be helpful. DISCUSSION: The results of the RECEPTS study will have
      important implications for providers of Primary Care. The study will establish
      current practice in UK primary care in terms of General Practice receptionists'
      knowledge of the presentation and appropriate referral of those who may be
      suffering a stroke. It will highlight training needs and how such training might
      be best delivered.

PMID- 24884884
TI  - In vitro inhibition of HUVECs by low dose methotrexate - insights into oral
      adverse events.
AB  - BACKGROUND: With socio-economic changes, dentists and maxillofacial surgeons are
      more and more faced with medically compromised patients. Especially, the
      admission of antirheumatic drugs has increased remarkably. So dentists and
      maxillofacial surgeons should be aware of related adverse reactions that affect
      the craniofacial region. To identify possible cellular effects of disease
      modifying antirheumatic drugs (DMARDs) we investigated the influence of
      methotrexate (MTX) on human umbilical vein endothelial cells (HUVECs). METHODS:
      HUVECs were incubated with various concentrations of MTX, corresponding to serum
      concentrations found in rheumatoid arthritis (RA) patients. The effect of MTX on
      cell proliferation, differentiation as well as mitochondrial activity was
      measured by use of immunostaining, cell counting and 3-(4, 5-dimethylthiazol-2
      yl)- 2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: All samples incubated
      with MTX (1-1000 nM) showed significantly decreased cell viability when compared
      to controls. Cells were less proliferating, but did not lose their ability to
      synthesize endothelial proteins. A slight dose dependency of inhibiting effects
      was demonstrated. The observed differences between control and sample groups were
      rising with longer duration. CONCLUSION: Because of the crucial role of
      endothelial cells and their precursor cells in wound healing, a negative
      influence of MTX on oral health has to be supposed, correlating to clinical
      observations of adverse reactions in the oral cavity, such as ulcerative or
      erosive lesions.

PMID- 24884886
TI  - Exogenous estradiol improves shell strength in laying hens at the end of the
      laying period.
AB  - BACKGROUND: Cracked shells, due to age related reduction of shell quality, are a
      costly problem for the industry. Parallel to reduced shell quality the skeleton
      becomes brittle resulting in bone fractures. Calcium, a main prerequisite for
      both eggshell and bone, is regulated by estrogen in a complex manner. The effects
      of estrogen, given in a low continuous dose, were studied regarding factors
      involved in age related changes in shell quality and bone strength of laying
      hens. A pellet containing 0.385 mg estradiol 3-benzoate (21-day-release) or
      placebo was inserted subcutaneously in 20 birds each of Lohmann Selected Leghorn
      (LSL) and Lohmann Brown (LB) at 70 weeks of age. Eggs were collected before and
      during the experiment for shell quality measurements. Blood samples for analysis
      of total calcium were taken three days after the insertion and at sacrifice (72
      weeks). Right femur was used for bone strength measurements and tissue samples
      from duodenum and shell gland were processed for morphology, immunohistochemical
      localization of estrogen receptors (ERalpha, ERbeta), plasma membrane calcium
      ATPase (PMCA) and histochemical localization of carbonic anhydrase (CA). RESULTS:
      Estrogen treatment increased shell thickness of both hybrids. In addition, shell
      weight and shell deformation improved in eggs from the brown hybrids. The more
      pronounced effect on eggs from the brown hybrid may be due to a change in
      sensitivity to estrogen, especially in surface epithelial cells of the shell
      gland, shown as an altered ratio between ERalpha and ERbeta. A regulatory effect
      of estrogen on CA activity, but not PMCA, was seen in both duodenum and shell
      gland, and a possible connection to shell quality is discussed. Bone strength was
      unaffected by treatment, but femur was stronger in LSL birds suggesting that the
      hybrids differ in calcium allocation between shell and bone at the end of the
      laying period. Plasma calcium concentrations and egg production were unaffected.
      CONCLUSIONS: A low continuous dose of estrogen improves shell strength but not
      bone strength in laying hens at the end of the laying period.

PMID- 24884887
TI  - Interplacental uterine expression of genes involved in prostaglandin synthesis
      during canine pregnancy and at induced prepartum luteolysis/abortion.
AB  - BACKGROUND: In the non-pregnant dog, ovarian cyclicity is independent of a
      uterine luteolysin. This is in contrast to pregnant animals where a prepartum
      increase of luteolytic PGF2alpha occurs, apparently originating in the pregnant
      uterus. Recently, the placenta as a source of prepartum prostaglandins (PGs) was
      investigated, indicating fetal trophoblast cells as the likely main source.
      However, the possible contribution of uterine interplacental tissues to the
      production of these hormones has not yet been thoroughly examined in the dog.
      METHODS: Several key factors involved in the production and/or actions of PGs
      were studied: cyclooxygenase 2 (COX2, PTGS2), PGF2alpha-synthase (PGFS/AKR1C3),
      PGE2-synthase (PGES), and the respective receptors FP (PTGFR), EP2 (PTGER2) and
      EP4 (PGTER4), 15-hydroxyprostaglandin dehydrogenase (HPGD), PG-transporter (PGT,
      SLCO2A1) and progesterone receptor. Their expression and localization patterns
      were assessed by Real Time PCR and immunohistology in the interplacental uterine
      sites from pregnant dogs during the pre-implantation period (days 8-12), post
      implantation (days 18-25), mid-gestation (days 35-40) and during antigestagen
      induced luteolysis/abortion. RESULTS: Whereas only low COX2 expression was
      observed in uterine samples at all the selected time points, expression of
      PGFS/AKR1C3 strongly increased post-implantation. A gradual increase in PGES-mRNA
      expression was noted towards mid-gestation. FP-mRNA expression decreased
      significantly with the progression of pregnancy until mid-gestation. This was
      associated with clearly detectable expression of HPGD, which did not change
      significantly over time. The expression of FP and EP2-mRNA decreased
      significantly over time while EP4-mRNA expression remained unaffected. The
      antigestagen-treatment led to a significant increase in expression of COX2, PGES,
      EP2 and PGT (SLCO2A1) mRNA. COX2 was localized predominantly in the myometrium.
      The expression of PGFS/AKR1C3, which was unchanged, was localized mostly to the
      surface luminal epithelium. The expression of EP4, PGT and HPGH did not change
      during treatment, they were co-localized with PGES and EP2 in all uterine
      compartments. CONCLUSIONS: The data clearly demonstrate the basic capability of
      the canine pregnant uterus to produce and respond to PGs and suggests their
      functions both as local regulatory factors involved in the establishment and
      maintenance of pregnancy, as well as potential contributors to the process of
      parturition, supporting the myometrial contractility associated with fetal
      expulsion.

PMID- 24884888
TI  - The development of a randomised controlled trial testing the effects of an online
      intervention among school students at risk of suicide.
AB  - BACKGROUND: Suicide-related behaviour among young people is of significant
      concern, yet little is known regarding the effectiveness of interventions
      designed to reduce risk among this population. Of those interventions that have
      been tested, cognitive-behavioural therapy appears to show some promise among
      young people with suicidal ideation. Internet-based interventions are becoming
      increasingly popular and have shown some effect in preventing and treating
      depression and anxiety in young people. However, to date there are no randomised
      controlled trials examining the impact of Internet-based Cognitive Behavioural
      Therapy among suicidal youth. METHODS/DESIGN: This is a randomised controlled
      trial testing the effects of Internet-based cognitive-behavioural therapy among
      suicidal high school students who have sought help from the school wellbeing
      team. The intervention comprises 8 modules of Cognitive Behavioural Therapy
      delivered online. The study has a staggered, two-year recruitment phase and
      participants are assessed at baseline, post intervention and 12 weeks later.
      DISCUSSION: If effective the program has the ability to be readily adapted and
      delivered to a range of populations in a range of settings, at relatively little
      cost. It can also be adapted for mobile applications. TRIAL REGISTRATION:
      ACTRN12613000864729. Date registered: 05/08/2013.

PMID- 24884885
TI  - Prevention of congenital malformations and other adverse pregnancy outcomes with
      4.0 mg of folic acid: community-based randomized clinical trial in Italy and the
      Netherlands.
AB  - BACKGROUND: In 2010 a Cochrane review confirmed that folic acid (FA)
      supplementation prevents the first- and second-time occurrence of neural tube
      defects (NTDs). At present some evidence from observational studies supports the
      hypothesis that FA supplementation can reduce the risk of all congenital
      malformations (CMs) or the risk of a specific and selected group of them, namely
      cardiac defects and oral clefts. Furthermore, the effects on the prevention of
      prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the
      most common recommendation is to take 0.4 mg/day, the problem of the most
      appropriate dose of FA is still open.The aim of this project is to assess the
      effect a higher dose of peri-conceptional FA supplementation on reducing the
      occurrence of all CMs. Other aims include the promotion of pre-conceptional
      counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm
      birth, small for gestational age, abruptio placentae. METHODS/DESIGN: This
      project is a joint effort by research groups in Italy and the Netherlands. Women
      of childbearing age, who intend to become pregnant within 12 months are eligible
      for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in
      study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy
      outcomes are derived from women-and-physician information.We foresee to analyze
      the data considering all the adverse outcomes of pregnancy taken together in a
      global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for
      gestational age). A total of about 1,000 pregnancies need to be evaluated to
      detect an absolute reduction of the frequency of 8%. Since the sample size needed
      for studying outcomes separately is large, this project also promotes an
      international prospective meta-analysis. DISCUSSION: The rationale of these
      randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is
      related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy
      outcomes. Our hope is that these trials will act as catalysers, and lead to other
      large RCTs studying the effects of this supplementation on CMs and other infant
      and maternal outcomes. TRIAL REGISTRATION: Italian trial: ClinicalTrials.gov
      Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161.

PMID- 24884889
TI  - Amyloid oligomers and protofibrils, but not filaments, self-replicate from native
      lysozyme.
AB  - Self-assembly of amyloid fibrils is the molecular mechanism best known for its
      connection with debilitating human disorders such as Alzheimer's disease but is
      also associated with various functional cellular responses. There is increasing
      evidence that amyloid formation proceeds along two distinct assembly pathways
      involving either globular oligomers and protofibrils or rigid monomeric
      filaments. Oligomers, in particular, have been implicated as the dominant
      molecular species responsible for pathogenesis. Yet the molecular mechanisms
      regulating their self-assembly have remained elusive. Here we show that
      oligomers/protofibrils and monomeric filaments, formed along distinct assembly
      pathways, display critical differences in their ability to template amyloid
      growth at physiological vs denaturing temperatures. At physiological
      temperatures, amyloid filaments remained stable but could not seed growth of
      native monomers. In contrast, oligomers and protofibrils not only remained intact
      but were capable of self-replication using native monomers as the substrate.
      Kinetic data further suggested that this prion-like growth mode of
      oligomers/protofibrils involved two distinct activities operating orthogonal from
      each other: autocatalytic self-replication of oligomers from native monomers and
      nucleated polymerization of oligomers into protofibrils. The environmental
      changes to stability and templating competence of these different amyloid species
      in different environments are likely to be important for understanding the
      molecular mechanisms underlying both pathogenic and functional amyloid self
      assembly. 

PMID- 24884890
TI  - Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an
      observational cohort.
AB  - BACKGROUND: There is limited data available regarding safety profile of
      artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a
      first-line treatment for malaria in first trimester due to associated embryo
      foetal toxicity in animal studies. The study assessed birth outcome among
      pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first
      trimester in comparison to those of women exposed to other anti-malarial drugs or
      no drug at all during the same period of pregnancy. METHODS: Pregnant women with
      gestational age <20 weeks were recruited from Maternal Health clinics or from
      monthly house visits (demographic surveillance), and followed prospectively until
      delivery. RESULTS: 2167 pregnant women were recruited and 1783 (82.3%) completed
      the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of
      whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine
      pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester
      was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1)
      and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for
      miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital
      anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]),
      quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group
      (19/1464[1.3%]). CONCLUSION: Exposure to AL in first trimester was more common
      than to any other anti-malarial drugs. Quinine exposure was associated with
      adverse pregnancy outcomes which was not the case following other anti-malarial
      intake. Since AL and quinine were used according to their availability rather
      than to disease severity, it is likely that the effect observed was related to
      the drug and not to the disease itself. Even with this caveat, a change of policy
      from quinine to AL for the treatment of uncomplicated malaria during the whole
      pregnancy period could be already envisaged.

PMID- 24884891
TI  - Gender differences in general and specialty outpatient mental health service use
      for depression.
AB  - BACKGROUND: This study ascertained gender-specific determinants of outpatient
      mental health (MH) service use for depression to highlight any gender disparities
      in barriers to care and explain how depressed men and women in need of care might
      differ in their help-seeking behaviour. METHODS: Data used in this study came
      from the Canadian Community Health Survey on Mental Health and Well Being, cycle
      1.2 (CCHS 1.2) conducted by Statistics Canada in 2002 (N = 36,984). The sample
      was limited to respondents filling criteria for a probable major depression in
      the 12 months prior to the interview (n = 1743). Gender-specific multivariate
      logistic regression analyses were carried out. RESULTS: The results showed that
      54.3% of respondents meeting criteria for major depression had consulted for
      mental health reasons in the year prior to interview. When looking at type of
      outpatient mental health service use, males were more likely to consult a general
      practitioner and a mental health specialist in the past year as opposed to
      females. However, females were more likely to consult a general practitioner only
      as opposed to no service use than males. Gender specific differences in
      determinants associated with outpatient service use included for males, lower
      adjusted household income, and for females, a younger age, the presence of social
      support, self-reported availability barriers, the presence of self-reported
      suicidal thoughts or attempt and a poorer self- perceived mental health.
      CONCLUSIONS: Continued efforts to promote access to mental health care are needed
      for men and women affected by depression, and this, to target specific vulnerable
      populations and increase utilization rates.

PMID- 24884893
TI  - The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from
      an updated meta-analysis.
AB  - BACKGROUND NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a central role in
      catalyzing the two-electron reduction of quinoid compounds into hydroquinones.
      The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic
      activity, which may result in increased incidence of carcinomas including breast
      cancer. Previous studies investigating the association between NQO1 Pro187Ser
      polymorphism and breast cancer risk showed inconsistent results. We performed a
      meta-analysis to summarize the possible association. METHODS: All studies
      published from January 1966 to February 2014 on the association between NQO1
      Pro187Ser polymorphism and breast cancer risk were identified by searching
      electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical
      Literature database (CBM). The association between NQO1 Pro187Ser polymorphism
      and breast cancer risk was assessed by odds ratios (ORs) together with their 95%
      confidence intervals (CIs). RESULTS: Ten studies with 2,773 cases and 4,076
      controls were finally included in the meta-analysis. We did not observe a
      significant association between NQO1 Pro187Ser polymorphism and breast cancer
      risk when all studies were pooled into the meta-analysis. In subgroup analysis by
      ethnicity, significant increased breast cancer risk was found in Caucasians
      (Ser/Pro vs. Pro/Pro: OR=1.145, 95% CI=1.008-1.301, P=0.038; Ser/Ser+Ser/Pro vs.
      Pro/Pro: OR=1.177, 95% CI=1.041-1.331, P=0.009). When stratified by source of
      control, significant increased breast cancer risk was found in population-based
      studies (Ser/Pro vs. Pro/Pro: OR=1.180, 95% CI=1.035-1.344, P=0.013;
      Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.191, 95% CI=1.050-1.350, P=0.007). However, in
      subgroup analyses according to menopausal status, quality score, and HWE in
      controls, no any significant association was detected. CONCLUSIONS: Our meta
      analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed
      to the breast cancer susceptibility among Caucasians. Further large and well
      designed studies are needed to confirm this association. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1248639991252504.

PMID- 24884892
TI  - Deep-sequencing transcriptome analysis of low temperature perception in a desert
      tree, Populus euphratica.
AB  - BACKGROUND: Compared with other Populus species, Populus euphratica Oliv.
      exhibits better tolerance to abiotic stress, especially those involving extreme
      temperatures. However, little is known about gene regulation and signaling
      pathways involved in low temperature stress responses in this species. Recent
      development of Illumina/Solexa-based deep-sequencing technologies has accelerated
      the study of global transcription profiling under specific conditions. To
      understand the gene network controlling low temperature perception in P.
      euphratica, we performed transcriptome sequencing using Solexa sequence analysis
      to generate a leaf transcriptome at a depth of 10 gigabases for each sample.
      RESULTS: Using the Trinity method, 52,081,238 high-quality trimmed reads were
      assembled into a non-redundant set and 108,502 unigenes with an average length of
      1,047 bp were generated. After performing functional annotations by aligning all
      unigenes with public protein databases, 85,584 unigenes were annotated.
      Differentially expressed genes were investigated using the FPKM method by
      applying the Benjamini and Hochberg corrections. Overall, 2,858 transcripts were
      identified as differentially expressed unigenes in at least two samples and 131
      were assigned as unigenes expressed differently in all three samples. In 4 
      degrees C-treated sample and -4  degrees C-treated sample, 1,661 and 866
      differently expressed unigenes were detected at an estimated absolute log2-fold
      change of > 1, respectively. Among them, the respective number of up-regulated
      unigenes in C4 and F4 sample was 1,113 and 630, while the respective number of
      down-regulated ungenes is 548 and 236. To increase our understanding of these
      differentially expressed genes, we performed gene ontology enrichment and
      metabolic pathway enrichment analyses. A large number of early cold (below or
      above freezing temperature)-responsive genes were identified, suggesting that a
      multitude of transcriptional cascades function in cold perception. Analyses of
      multiple cold-responsive genes, transcription factors, and some key transduction
      components involved in ABA and calcium signaling revealed their potential
      function in low temperature responses in P. euphratica. CONCLUSIONS: Our results
      provide a global transcriptome picture of P. euphratica under low temperature
      stress. The potential cold stress related transcripts identified in this study
      provide valuable information for further understanding the molecular mechanisms
      of low temperature perception in P. euphratica.

PMID- 24884895
TI  - Concentration and purification of enterovirus 71 using a weak anion-exchange
      monolithic column.
AB  - BACKGROUND: Enterovirus 71 (EV-71) is a neurotropic virus causing Hand, Foot and
      Mouth Disease (HFMD) in infants and children under the age of five. It is a major
      concern for public health issues across Asia-Pacific region. The most effective
      way to control the disease caused by EV-71 is by vaccination thus a novel vaccine
      is urgently needed. Inactivated EV-71 induces a strong, virus-neutralizing
      antibody response in animal models, protecting them against a lethal EV-71
      challenge and it has been shown to elicit cross-neutralizing antibodies in human
      trials. Hence, the large-scale production of purified EV-71 is required for
      vaccine development, diagnosis and clinical trials. METHODS: CIM(r) Monolith
      columns are single-piece columns made up of poly(glycidyl methacrylate co
      ethylene dimethacrylate) as support matrix. They are designed as porous channels
      rather than beads with different chemistries for different requirements. As
      monolithic columns have a high binding capacity, flow rate and resolution, a
      CIM(r) DEAE-8f tube monolithic column was selected for purification in this
      study. The EV-71 infected Rhabdomyosarcoma (RD) cell supernatant was concentrated
      using 8% PEG 8000 in the presence of 400 mM sodium chloride. The concentrated
      virus was purified by weak anion exchange column using 50 mM HEPES + 1 M sodium
      chloride as elution buffer. RESULTS: Highly pure viral particles were obtained at
      a concentration of 350 mM sodium chloride as confirmed by SDS-PAGE and electron
      microscopy. Presence of viral proteins VP1, VP2 and VP3 was validated by western
      blotting. The overall process achieved a recovery of 55%. CONCLUSIONS: EV-71
      viral particles of up to 95% purity can be recovered by a single step ion
      exchange chromatography using CIM-DEAE monolithic columns and 1 M sodium chloride
      as elution buffer. Moreover, this method is scalable to purify several litres of
      virus-containing supernatant, using industrial monolithic columns with a capacity
      of up to 8 L such as CIM(r) cGMP tube monolithic columns.

PMID- 24884894
TI  - Prevalence and correlates of diabetes mellitus in Malawi: population-based
      national NCD STEPS survey.
AB  - BACKGROUND: Previously considered as a disease of the affluent, west or urban
      people and not of public health importance, diabetes mellitus is increasingly
      becoming a significant cause of morbidity and mortality in sub-Saharan Africa.
      However, population-based data to inform prevention, treatment and control are
      lacking. METHODS: Using the WHO STEPwise approach to chronic disease risk factor
      surveillance, a population-based, nationwide cross-sectional survey was conducted
      between July and September 2009 on participants aged 25-64 years. A multi-stage
      cluster sample design and weighting were used to produce a national
      representative data for that age range. Detailed findings on the magnitude of
      diabetes mellitus and impaired fasting blood glucose are presented in this paper.
      RESULTS: Fasting blood glucose measurement was conducted on 3056 participants
      (70.2% females, 87.9% from rural areas). The age- sex standardised population
      based mean fasting blood glucose was 4.3 mmol/L (95% CI 4.1-4.4 mmol/L) with no
      significant differences by age, sex and location (urban/rural). The overall
      prevalence of impaired fasting blood glucose was 4.2% (95% CI 3.0%-5.4%).
      Prevalence of impaired blood glucose was higher in men than in women, 5.7% (95%
      CI 3.9%-7.5%) vs 2.7% (95% CI 1.6%- 3.8%), p < 0.01. In both men and women,
      prevalence of raised fasting blood glucose or currently on medication for
      diabetes was 5.6% (95% CI 2.6%- 8.5%). Although the prevalence of diabetes was
      higher in men than women, 6.5% (95% CI 2.6%-10.3%) vs 4.7% (95% CI 2.4%-7.0%), in
      rural than urban, 5.4% (95% CI 2.4%-8.4%) vs 4.4% (95% CI 2.8%-5.9%) and in males
      in rural than males in urban, 6.9% (95% CI 2.8%-11.0%) vs 3.2% (95% CI 0.1%
      6.3%), the differences were not statistically significant, p > 0.05. Compared to
      previous estimates, prevalence of diabetes increased from <1.0% in 1960s to 5.6%
      in 2009 (this study). CONCLUSION: High prevalence of impaired fasting blood
      glucose and diabetes mellitus call for the implementation of primary healthcare
      approaches such as the WHO package for essential non-communicable diseases to
      promote healthy lifestyles, early detection, treatment and control.

PMID- 24884896
TI  - Lactobacillus delbrueckii ssp. lactis and ssp. bulgaricus: a chronicle of
      evolution in action.
AB  - BACKGROUND: Lactobacillus delbrueckii ssp. lactis and ssp. bulgaricus are lactic
      acid producing bacteria that are largely used in dairy industries, notably in
      cheese-making and yogurt production. An earlier in-depth study of the first
      completely sequenced ssp. bulgaricus genome revealed the characteristics of a
      genome in an active phase of rapid evolution, in what appears to be an adaptation
      to the milk environment. Here we examine for the first time if the same
      conclusions apply to the ssp. lactis, and discuss intra- and inter-subspecies
      genomic diversity in the context of evolutionary adaptation. RESULTS: Both L.
      delbrueckii ssp. show the signs of reductive evolution through the elimination of
      superfluous genes, thereby limiting their carbohydrate metabolic capacities and
      amino acid biosynthesis potential. In the ssp. lactis this reductive evolution
      has gone less far than in the ssp. bulgaricus. Consequently, the ssp. lactis
      retained more extended carbohydrate metabolizing capabilities than the ssp.
      bulgaricus but, due to high intra-subspecies diversity, very few carbohydrate
      substrates, if any, allow a reliable distinction of the two ssp. We further show
      that one of the most important traits, lactose fermentation, of one of the
      economically most important dairy bacteria, L. delbruecki ssp. bulgaricus, relies
      on horizontally acquired rather than deep ancestral genes. In this sense this
      bacterium may thus be regarded as a natural GMO avant la lettre. CONCLUSIONS: The
      dairy lactic acid producing bacteria L. delbrueckii ssp. lactis and ssp.
      bulgaricus appear to represent different points on the same evolutionary track of
      adaptation to the milk environment through the loss of superfluous functions and
      the acquisition of functions that allow an optimized utilization of milk
      resources, where the ssp. bulgaricus has progressed further away from the common
      ancestor.

PMID- 24884898
TI  - Intraductal papilloma in an axillary lymph node of a patient with human
      immunodeficiency virus: a case report and review of the literature.
AB  - INTRODUCTION: Inclusions of ectopic breast tissue in axillary lymph nodes are
      reported very infrequently and typically are only identified microscopically as
      an incidental finding. Furthermore the development of a benign proliferative
      lesion in the form of an intraductal papilloma from intranodal ectopic breast
      tissue is an extremely rare phenomenon with only three previous cases reported.
      This report describes an unusual and rare case of an intraductal papilloma
      arising in an axillary lymph node of a patient known to have the human
      immunodeficiency virus. CASE PRESENTATION: A 40-year-old Black African woman
      underwent excision of an enlarged palpable axillary lymph node. In the preceding
      7 years she had received at least six separate surgical excisions to her
      ipsilateral breast for papillomatosis. The last surgical intervention was
      performed 1 year prior to presentation with an enlarged axillary lymph node.
      Histological examination of her axillary lymph node revealed a papillomatous
      proliferative epithelial lesion within an apparent encompassing duct, resembling
      a mammary intraductal papilloma. In the surrounding lymphoid tissue small groups
      of duct-like structures were additionally noted. Immunostaining with a panel of
      myoepithelial markers in conjunction with oestrogen receptor produced a mixed
      heterogeneous staining pattern in both the papillomatous lesion and the
      peripheral duct-like structures. This confirmed the diagnosis of a benign
      intraductal papilloma within an axillary lymph node, considered to have arisen
      from ectopic breast tissue. CONCLUSIONS: This case demonstrates that intranodal
      ectopic breast tissue has the potential to undergo benign proliferative change
      albeit extremely rarely. Therefore this possibility must be considered to ensure
      the correct diagnosis is made. In addition, to the best of our knowledge, this is
      the first case report which has described recurrent intraductal papillomas and
      the subsequent development of an intraductal papilloma within an ipsilateral
      axillary lymph node, in a patient who is human immunodeficiency virus positive.
      There is minimal literature investigating the specific types of breast
      pathologies experienced by patients infected with human immunodeficiency virus
      and it remains unexplored as to whether human immunodeficiency virus may lead to
      proliferative papillomatous epithelial changes. This report considers the role of
      the human papillomavirus and recommends that further investigatory studies are
      required.

PMID- 24884897
TI  - Bevacizumab with 5-fluorouracil, leucovorin, and oxaliplatin versus bevacizumab
      with capecitabine and oxaliplatin for metastatic colorectal carcinoma: results of
      a large registry-based cohort analysis.
AB  - BACKGROUND: Data from the Czech national registry were analysed retrospectively
      to describe treatment outcomes for capecitabine and oxaliplatin (XELOX) regimen
      with bevacizumab versus 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)
      regimen with bevacizumab in the first-line therapy for metastatic colorectal
      cancer (mCRC). METHODS: A national registry containing anonymised individual data
      on patients treated with targeted therapies was used as a data source. In total,
      2,191 mCRC patients who received a first-line therapy with bevacizumab combined
      with either FOLFOX regimen (n = 1,218, 55.6%) or XELOX regimen (n = 973, 44.4%)
      were included in the present analysis. RESULTS: No statistically significant
      difference in survival was observed between the two groups, with median overall
      survival (OS) of 27.0 months (95% confidence interval [CI] 24.6-29.5 months) and
      30.6 months (95% CI 27.8-33.4 months) for FOLFOX/bevacizumab and
      XELOX/bevacizumab, respectively (p = 0.281). Median progression-free survival
      (PFS) was 11.4 months (95% CI 10.7-12.1 months) for FOLFOX/bevacizumab and 11.5
      months (95% CI 10.8-12.3 months) for XELOX/bevacizumab (p = 0.337). The number of
      metastatic sites was identified as the most significant predictor of PFS and,
      together with the presence/absence of metastatic disease at diagnosis, also for
      OS. CONCLUSIONS: According to this large registry-based analysis, XELOX and
      FOLFOX regimens have similar effectiveness for use in combination with
      bevacizumab in the first-line treatment of mCRC. Multiple metastatic sites and
      the presence of metastatic disease at diagnosis were the strongest negative
      predictors of OS regardless of backbone chemotherapy regimen.

PMID- 24884899
TI  - An educational video to promote multi-factorial approaches for fall and injury
      prevention in long-term care facilities.
AB  - BACKGROUND: Older adults living in long term care (LTC) settings are vulnerable
      to fall-related injuries. There is a need to develop and implement evidence-based
      approaches to address fall injury prevention in LTC. Knowledge translation (KT)
      interventions to support the uptake of evidence-based approaches to fall injury
      prevention in LTC need to be responsive to the learning needs of LTC staff and
      use mediums, such as videos, that are accessible and easy-to-use. This article
      describes the development of two unique educational videos to promote fall injury
      prevention in long-term care (LTC) settings. These videos are unique from other
      fall prevention videos in that they include video footage of real life falls
      captured in the LTC setting. METHODS: Two educational videos were developed (2012
      2013) to support the uptake of findings from a study exploring the causes of
      falls based on video footage captured in LTC facilities. The videos were
      developed by: (1) conducting learning needs assessment in LTC settings via six
      focus groups (2) liaising with LTC settings to identify learning priorities
      through unstructured conversations; and (3) aligning the content with principles
      of adult learning theory. RESULTS: The videos included footage of falls,
      interviews with older adults and fall injury prevention experts. The videos
      present evidence-based fall injury prevention recommendations aligned to the
      needs of LTC staff and: (1) highlight recommendations deemed by LTC staff as most
      urgent (learner-centered learning); (2) highlight negative impacts of falls on
      older adults (encourage meaning-making); and, (3) prompt LTC staff to reflect on
      fall injury prevention practices (encourage critical reflection). CONCLUSIONS:
      Educational videos are an important tool available to researchers seeking to
      translate evidence-based recommendations into LTC settings. Additional research
      is needed to determine their impact on practice.

PMID- 24884900
TI  - Advancing geriatric education: development of an interprofessional program for
      health care faculty.
AB  - To improve the health care of older adults, a faculty development program was
      created to enhance geriatric knowledge. The University of Alabama at Birmingham
      (UAB) Geriatric Education Center leadership instituted a one-year, 36-hour
      curriculum focusing on older adults with complex health care needs. Content areas
      were chosen from the Institute of Medicine Transforming Health Care Quality
      report and a local needs assessment. Potential preceptors were identified and
      participant recruitment efforts began by contacting UAB department chairs of
      health care disciplines. This article describes the development of the program
      and its implementation over three cohorts of faculty scholars (n = 41)
      representing 13 disciplines, from nine institutions of higher learning. Formative
      and summative evaluation showed program success in terms of positive faculty
      reports of the program, information gained, and expressed intent by each scholar
      to apply learned content to teaching and/or clinical practice. This article
      describes the initial framework and strategies guiding the development of a
      thriving interprofessional geriatric education program. 

PMID- 24884901
TI  - Structural evolution of CatSper1 in rodents is influenced by sperm competition,
      with effects on sperm swimming velocity.
AB  - BACKGROUND: Competition between spermatozoa from rival males for success in
      fertilization (i.e., sperm competition) is an important selective force driving
      the evolution of male reproductive traits and promoting positive selection in
      genes related to reproductive function. Positive selection has been identified in
      reproductive proteins showing rapid divergence at nucleotide level. Other
      mutations, such as insertions and deletions (indels), also occur in protein
      coding sequences. These structural changes, which exist in reproductive genes and
      result in length variation in coded proteins, could also be subjected to positive
      selection and be under the influence of sperm competition. Catsper1 is one such
      reproductive gene coding for a germ-line specific voltage-gated calcium channel
      essential for sperm motility and fertilization. Positive selection appears to
      promote fixation of indels in the N-terminal region of CatSper1 in mammalian
      species. However, it is not known which selective forces underlie these changes
      and their implications for sperm function. RESULTS: We tested if length variation
      in the N-terminal region of CatSper1 is influenced by sperm competition intensity
      in a group of closely related rodent species of the subfamily Murinae. Our
      results revealed a negative correlation between sequence length of CatSper1 and
      relative testes mass, a very good proxy of sperm competition levels. Since
      CatSper1 is important for sperm flagellar motility, we examined if length
      variation in the N-terminus of CatSper1 is linked to changes in sperm swimming
      velocity. We found a negative correlation between CatSper1 length and several
      sperm velocity parameters. CONCLUSIONS: Altogether, our results suggest that
      sperm competition selects for a shortening of the intracellular region of
      CatSper1 which, in turn, enhances sperm swimming velocity, an essential and
      adaptive trait for fertilization success.

PMID- 24884902
TI  - Effects of aromatic compounds on the production of bacterial nanocellulose by
      Gluconacetobacter xylinus.
AB  - BACKGROUND: Bacterial cellulose (BC) is a polymeric nanostructured fibrillar
      network produced by certain microorganisms, principally Gluconacetobacter
      xylinus. BC has a great potential of application in many fields. Lignocellulosic
      biomass has been investigated as a cost-effective feedstock for BC production
      through pretreatment and hydrolysis. It is well known that detoxification of
      lignocellulosic hydrolysates may be required to achieve efficient production of
      BC. Recent results suggest that phenolic compounds contribute to the inhibition
      of G. xylinus. However, very little is known about the effect on G. xylinus of
      specific lignocellulose-derived inhibitors. In this study, the inhibitory effects
      of four phenolic model compounds (coniferyl aldehyde, ferulic acid, vanillin and
      4-hydroxybenzoic acid) on the growth of G. xylinus, the pH of the culture medium,
      and the production of BC were investigated in detail. The stability of the
      phenolics in the bacterial cultures was investigated and the main bioconversion
      products were identified and quantified. RESULTS: Coniferyl aldehyde was the most
      potent inhibitor, followed by vanillin, ferulic acid, and 4-hydroxybenzoic acid.
      There was no BC produced even with coniferyl aldehyde concentrations as low as 2
      mM. Vanillin displayed a negative effect on the bacteria and when the vanillin
      concentration was raised to 2.5 mM the volumetric yield of BC decreased to ~40%
      of that obtained in control medium without inhibitors. The phenolic acids,
      ferulic acid and 4-hydroxybenzoic acid, showed almost no toxic effects when less
      than 2.5 mM. The bacterial cultures oxidized coniferyl aldehyde to ferulic acid
      with a yield of up to 81%. Vanillin was reduced to vanillyl alcohol with a yield
      of up to 80%. CONCLUSIONS: This is the first investigation of the effect of
      specific phenolics on the production of BC by G. xylinus, and is also the first
      demonstration of the ability of G. xylinus to convert phenolic compounds. This
      study gives a better understanding of how phenolic compounds and G. xylinus
      cultures are affected by each other. Investigations in this area are useful for
      elucidating the mechanism behind inhibition of G. xylinus in lignocellulosic
      hydrolysates and for understanding how production of BC using lignocellulosic
      feedstocks can be performed in an efficient way.

PMID- 24884903
TI  - The role of social networks in adult health: introduction to the special issue.
AB  - The goal of this special issue is to highlight recent research examining the role
      of social networks in adults' physical health.

PMID- 24884904
TI  - Who needs a friend? Marital status transitions and physical health outcomes in
      later life.
AB  - OBJECTIVE: This study assessed the moderating role of 2 types of confidante
      relationships in mitigating the negative health impact of transitions involving
      spousal loss in late life (widowhood and divorce/separation). METHOD: The sample
      included 707 respondents who participated in the 1992 and 2004 waves of the
      Wisconsin Longitudinal Study (WLS, 2007) all of whom were married at Time 1 and
      by Time 2 experienced either an end of the marriage resulting from widowhood or
      divorce/separation or remained continuously married to the same spouse. The
      majority of the sample was female (n = 457) and 64.3 years old on average. Three
      indicators of physical health were examined, including somatic depressive
      symptomatology, self-rated health, and number of sick days in the preceding year.
      RESULTS: Moderated regression analyses showed that the availability of a friend
      as confidante at Time 2 played a significant moderating role in the link between
      marital transitions and health outcomes, buffering the health impact of
      widowhood. Specifically, among those who became widowed between the 2 waves,
      those who had available a friend as confidante at Time 2 reported significantly
      lower somatic depressive symptoms, better self-rated health, and fewer sick days
      in bed during the preceding year than those who reported not having a friend as
      confidante. No support was obtained for the moderating role of having a family
      member as confidante at Time 2 in the link from marital transitions to health.
      CONCLUSIONS: These results highlight the need to develop means to maintain and
      enhance confiding friendships among widowed older adults.

PMID- 24884905
TI  - Social relationships, leisure activity, and health in older adults.
AB  - OBJECTIVE: Although the link between enhanced social relationships and better
      health has generally been well established, few studies have examined the role of
      leisure activity in this link. This study examined how leisure influences the
      link between social relationships and health in older age. METHOD: Using data
      from the 2006 and 2010 waves of the nationally representative U.S. Health and
      Retirement Study and structural equation modeling analyses, we examined data on
      2,965 older participants to determine if leisure activities mediated the link
      between social relationships and health in 2010, controlling for race, education
      level, and health in 2006. RESULTS: The results demonstrated that leisure
      activities mediate the link between social relationships and health in these age
      groups. Perceptions of positive social relationships were associated with greater
      involvement in leisure activities, and greater involvement in leisure activities
      was associated with better health in older age. CONCLUSION: The contribution of
      leisure to health in these age groups is receiving increasing attention, and the
      results of this study add to the literature on this topic, by identifying the
      mediating effect of leisure activity on the link between social relationships and
      health. Future studies aimed at increasing leisure activity may contribute to
      improved health outcomes in older adults.

PMID- 24884906
TI  - Physical and social activities mediate the associations between social network
      types and ventilatory function in Chinese older adults.
AB  - OBJECTIVE: This study examined the associations between social network types and
      peak expiratory flow (PEF), and whether these associations were mediated by
      social and physical activities and mood. METHOD: Nine hundred twenty-four
      community-dwelling Chinese older adults, who were classified into five network
      types (diverse, friend-focused, family-focused, distant family, and restricted),
      provided data on demographics, social and physical activities, mood, smoking,
      chronic diseases, and instrumental activities of daily living. PEF and biological
      covariates, including blood lipids and glucose, blood pressure, and height and
      weight, were assessed. Two measures of PEF were analyzed: the raw reading in
      L/min and the reading expressed as percentage of predicted normal value on the
      basis of age, sex, and height. Diverse, friend-focused, and distant family
      networks were hypothesized to have better PEF values compared with restricted
      networks, through higher physical and/or social activities. No relative advantage
      was predicted for family-focused networks because such networks tend to be
      associated with lower physical activity. RESULTS: Older adults with diverse,
      friend-focused, and distant family networks had significantly better PEF measures
      than those with restricted networks. The associations between diverse network and
      PEF measures were partially mediated by physical exercise and socializing
      activity. The associations between friend-focused network and PEF measures were
      partially mediated by socializing activity. No significant PEF differences
      between family-focused and restricted networks were found. CONCLUSIONS: Findings
      suggest that social network types are associated with PEF in older adults, and
      that network-type differences in physical and socializing activity is partly
      responsible for this relationship.

PMID- 24884907
TI  - Social integration and pulmonary function in the elderly.
AB  - OBJECTIVE: This study sought to determine whether social integration, defined as
      number of social roles, is associated with better pulmonary function in the
      elderly and which roles are associated with greatest benefit. It also examined
      pathways that connect social integration to better lung health. METHODS: High
      functioning men (n = 518) and women (n = 629) ages 70-79 were recruited as part
      of the MacArthur Study of Successful Aging, and data were collected on social
      roles as well as pulmonary function as assessed by peak expiratory flow rate
      (PEFR). Multiple regressions predicting PEFR from the number of social roles
      controlled for age, sex, race, education, weight, and height. Physiological,
      behavioral, social, and psychological factors were tested as mediators of the
      association between the number of social roles and PEFR. RESULTS: More social
      roles were associated with better PEFR. Analysis of specific roles indicated that
      marriage was the strongest positive correlate of PEFR. However, greater numbers
      of roles were also associated with better PEFR independent of marriage. Being a
      relative or friend were each also individually associated with better PEFR. Even
      so, greater numbers of social roles were associated with better PEFR independent
      of relative and friend. The data were consistent with greater happiness, not
      smoking, and more physical activity acting as pathways linking the number of
      roles to PEFR. CONCLUSIONS: Number of social roles is an important correlate of
      healthy lung function in the elderly. This association may be driven by healthier
      behaviors and greater feelings of well-being.

PMID- 24884908
TI  - Social network characteristics associated with health promoting behaviors among
      Latinos.
AB  - OBJECTIVE: This study examined the relationship between social network
      characteristics and health promoting behaviors (having a routine medical check
      up, consuming no alcohol, consuming no fast food, and meeting recommendations for
      leisure-time physical activity and sleep duration) among Latinos to identify
      potential targets for behavioral interventions. METHOD: Personal network
      characteristics and health behavior data were collected from a community sample
      of 393 adult Latinos (73% women) in San Diego County, California. Network
      characteristics consisted of size and composition. Network size was calculated by
      the number of alters listed on a name generator questionnaire eliciting people
      with whom respondents discussed personal issues. Network composition variables
      were the proportion of Latinos, Spanish-speakers, females, family, and friends
      listed in the name generator. Additional network composition variables included
      marital status and the number of adults or children in the household. RESULTS:
      Network members were predominately Latinos (95%), Spanish-speakers (80%), females
      (64%), and family (55%). In multivariate logistic regression analyses, gender
      moderated the relationship between network composition, but not size, and a
      health behavior. Married women were more likely to have had a routine medical
      check-up than married men. For both men and women, having a larger network was
      associated with meeting the recommendation for leisure-time physical activity.
      CONCLUSION: Few social network characteristics were significantly associated with
      health promoting behaviors, suggesting a need to examine other aspects of social
      relationships that may influence health behaviors.

PMID- 24884909
TI  - Negative social interactions and incident hypertension among older adults.
AB  - OBJECTIVE: To determine if negative social interactions are prospectively
      associated with hypertension among older adults. METHOD: This is a secondary
      analysis of data from the 2006 and 2010 waves of the Health and Retirement Study,
      a survey of community-dwelling older adults (age > 50 years). Total average
      negative social interactions were assessed at baseline by averaging the frequency
      of negative interactions across 4 domains (partner, children, other family,
      friends). Blood pressure was measured at both waves. Individuals were considered
      to have hypertension if they reported use of antihypertensive medications, had
      measured average resting systolic blood pressure of 140 mmHg or higher, or
      measured average resting diastolic blood pressure of 90 mmHg or higher. Analyses
      excluded those who were hypertensive at baseline and controlled for demographics,
      personality, positive social interactions, and baseline health. RESULTS: Twenty
      nine percent of participants developed hypertension over the 4-year follow-up.
      Each 1-unit increase in the total average negative social interaction score was
      associated with a 38% increased odds of developing hypertension. Sex moderated
      the association between total average negative social interactions and
      hypertension, with effects observed among women but not men. The association of
      total average negative interactions and hypertension in women was attributable
      primarily to interactions with friends, but also to negative interactions with
      family and partners. Age also moderated the association between total average
      negative social interactions and hypertension, with effects observed among those
      ages 51-64 years, but not those ages 65 or older. CONCLUSION: In this sample of
      older adults, negative social interactions were associated with increased
      hypertension risk in women and the youngest older adults.

PMID- 24884910
TI  - Dyadic collaboration in shared health behavior change: the effects of a
      randomized trial to test a lifestyle intervention for high-risk Latinas.
AB  - OBJECTIVE: This study sought to evaluate the feasibility of a pilot, dyad-based
      lifestyle intervention, the Unidas por la Vida program, for improving weight loss
      and dietary intake among high-risk Mexican American mothers who have Type 2
      diabetes and their overweight/obese adult daughters. METHOD: Mother-daughter
      dyads (N = 89) were recruited from two federally qualified health centers and
      randomly assigned to either the Unidas intervention or to the control condition.
      The 16-week Unidas intervention consisted of the following: (a) four group
      meetings, (b) eight home visits, and (c) booster telephone calls by a lifestyle
      community coach. The control condition consisted of educational materials mailed
      to participants' homes. Participants completed surveys at T1 (baseline) and T2
      (16 weeks) that assessed various demographic, social network involvement, and
      dietary variables. RESULTS: Unidas participants lost significantly more weight at
      T2 (p < .003) compared with the control participants. Furthermore, intervention
      participants also were more likely to be eating foods with lower glycemic load (p
      < .001) and less saturated fat (p = .004) at T2. Unidas participants also
      reported a significant increase in health-related social support and social
      control (persuasion control only) and a decrease in undermining. CONCLUSIONS: The
      Unidas program promoted weight loss and improved dietary intake, as well as
      changes in diet-related involvement of participants' social networks. The results
      from this study demonstrate that interventions that draw upon multiple people who
      share a health-risk have the potential to foster significant changes in lifestyle
      behaviors and in social network members' health-related involvement. Future
      research that builds on these findings is needed to elucidate the specific dyadic
      and social network processes that may drive health behavior change.

PMID- 24884911
TI  - Individual and work-related risk factors for musculoskeletal pain: a cross
      sectional study among Estonian computer users.
AB  - BACKGROUND: Occupational use of computers has increased rapidly over recent
      decades, and has been linked with various musculoskeletal disorders, which are
      now the most commonly diagnosed occupational diseases in Estonia. The aim of this
      study was to assess the prevalence of musculoskeletal pain (MSP) by anatomical
      region during the past 12 months and to investigate its association with personal
      characteristics and work-related risk factors among Estonian office workers using
      computers. METHODS: In a cross-sectional survey, the questionnaires were sent to
      the 415 computer users. Data were collected by self-administered questionnaire
      from 202 computer users at two universities in Estonia. The questionnaire asked
      about MSP at different anatomical sites, and potential individual and work
      related risk factors. Associations with risk factors were assessed by logistic
      regression. RESULTS: Most respondents (77%) reported MSP in at least one
      anatomical region during the past 12 months. Most prevalent was pain in the neck
      (51%), followed by low back pain (42%), wrist/hand pain (35%) and shoulder pain
      (30%). Older age, right-handedness, not currently smoking, emotional exhaustion,
      belief that musculoskeletal problems are commonly caused by work, and low job
      security were the statistically significant risk factors for MSP in different
      anatomical sites. CONCLUSIONS: A high prevalence of MSP in the neck, low back,
      wrist/arm and shoulder was observed among Estonian computer users. Psychosocial
      risk factors were broadly consistent with those reported from elsewhere. While
      computer users should be aware of ergonomic techniques that can make their work
      easier and more comfortable, presenting computer use as a serious health hazard
      may modify health beliefs in a way that is unhelpful.

PMID- 24884912
TI  - Renal metastasis after esophagectomy of esophageal squamous cell carcinoma: a
      case report and literature review.
AB  - Solitary metastatic renal tumors are rarely encountered. We report the case of a
      63-year-old man who developed a solitary renal metastasis after undergoing an
      esophagectomy for esophageal squamous cell carcinoma and subsequent nephrectomy
      of the right kidney. 

PMID- 24884913
TI  - On the association of common and rare genetic variation influencing body mass
      index: a combined SNP and CNV analysis.
AB  - BACKGROUND: As the architecture of complex traits incorporates a widening
      spectrum of genetic variation, analyses integrating common and rare variation are
      needed. Body mass index (BMI) represents a model trait, since common variation
      shows robust association but accounts for a fraction of the heritability. A
      combined analysis of single nucleotide polymorphisms (SNP) and copy number
      variation (CNV) was performed using 1850 European and 498 African-Americans from
      the Study of Addiction: Genetics and Environment. Genetic risk sum scores (GRSS)
      were constructed using 32 BMI-validated SNPs and aggregate-risk methods were
      compared: count versus weighted and proxy versus imputation. RESULTS: The
      weighted SNP-GRSS constructed from imputed probabilities of risk alleles
      performed best and was highly associated with BMI (p=4.3*10(-16)) accounting for
      3% of the phenotypic variance. In addition to BMI-validated SNPs, common and rare
      BMI/obesity-associated CNVs were identified from the literature. Of the 84 CNVs
      previously reported, only 21-kilobase deletions on 16p12.3 showed evidence for
      association with BMI (p=0.003, frequency=16.9%), with two CNVs nominally
      associated with class II obesity, 1p36.1 duplications (OR=3.1, p=0.009, frequency
      1.2%) and 5q13.2 deletions (OR=1.5, p=0.048, frequency 7.7%). All other CNVs,
      individually and in aggregate, were not associated with BMI or obesity. The
      combined model, including covariates, SNP-GRSS, and 16p12.3 deletion accounted
      for 11.5% of phenotypic variance in BMI (3.2% from genetic effects). Models
      significantly predicted obesity classification with maximum discriminative
      ability for morbid-obesity (p=3.15*10(-18)). CONCLUSION: Results show that
      incorporating validated effect sizes and allelic probabilities improve prediction
      algorithms. Although rare-CNVs did not account for significant phenotypic
      variation, results provide a framework for integrated analyses.

PMID- 24884914
TI  - Anal signs of child sexual abuse: a case-control study.
AB  - BACKGROUND: There is uncertainty about the nature and specificity of physical
      signs following anal child sexual abuse. The study investigates the extent to
      which physical findings discriminate between children with and without a history
      of anal abuse. METHODS: Retrospective case note review in a paediatric forensic
      unit. CASES: all eligible cases from 1990 to 2007 alleging anal abuse. CONTROLS:
      all children examined anally from 1998 to 2007 with possible physical abuse or
      neglect with no identified concern regarding sexual abuse. Fisher's exact test
      (two-tailed) was performed to ascertain the significance of differences for
      individual signs between cases and controls. To explore the potential role of
      confounding, logistic regression was used to produce odds ratios adjusted for age
      and gender. RESULTS: A total of 184 cases (105 boys, 79 girls), average age 98.5
      months (range 26 to 179) were compared with 179 controls (94 boys, 85 girls)
      average age 83.7 months (range 35-193). Of the cases 136 (74%) had one or more
      signs described in anal abuse, compared to 29 (16%) controls. 79 (43%) cases and
      2 (1.1%) controls had >1 sign. Reflex anal dilatation (RAD) and venous congestion
      were seen in 22% and 36% of cases but <1% of controls (likelihood ratios (LR) 40,
      60 respectively), anal fissure in 14% cases and 1.1% controls (LR 13), anal
      laxity in 27% cases and 3% controls (LR 10).Novel signs seen significantly more
      commonly in cases were anal fold changes, swelling and twitching. Erythema,
      swelling and fold changes were seen most commonly within 7 days of last reported
      contact; RAD, laxity, venous congestion, fissure and twitching were observed up
      to 6 months after the alleged assault. CONCLUSIONS: Anal findings are more common
      in children alleging anal abuse than in those presenting with physical abuse or
      neglect with no concern about sexual abuse. Multiple signs are rare in controls
      and support disclosed anal abuse.

PMID- 24884915
TI  - A large de novo 9p21.3 deletion in a girl affected by astrocytoma and multiple
      melanoma.
AB  - BACKGROUND: Association of melanoma, neural system tumors and germ line mutations
      at the 9p21 region in the CDKN2A, CDKN2B and CDKN2BAS genes has been reported in
      a small number of families worldwide and described as a discrete syndrome in
      melanoma families registered as a rare disease, the melanoma-astrocytoma
      syndrome. CASE PRESENTATION: We here studied two young patients developing
      melanoma after radiotherapy for astrocytoma, both reporting lack of family
      history for melanoma or neural system tumors at genetic counselling. Patient A is
      a girl treated for anaplastic astrocytoma at 10 years and for multiple melanomas
      on the scalp associated to dysplastic nevi two years later. Her monozygotic twin
      sister carried dysplastic nevi and a slow growing, untreated cerebral lesion.
      Direct sequencing analysis showed no alterations in melanoma susceptibility genes
      including CDKN2A, CDK4, MC1R and MITF or in TP53. By microsatellite analysis,
      multiplex ligation-dependent probe amplification, and array comparative genomic
      hybridization a deletion including the CDKN2A, CDKN2B and CDKN2BAS gene cluster
      was detected in both twin sisters, encompassing a large region at 9p21.3 and
      occurring de novo after the loss of one paternal allele.Patient B is a boy of 7
      years when treated for astrocytoma then developing melanoma associated to
      congenital nevi on the head 10 years later: sequencing and multiplex ligation
      dependent probe amplification revealed a normal profile of the
      CDKN2A/CDKN2B/CDKN2BAS region. Array comparative genomic hybridization confirmed
      the absence of deletions at 9p21.3 and failed to reveal known pathogenic copy
      number variations. CONCLUSIONS: By comparison with the other germ line deletions
      at the CDKN2A, CDKN2B and CDKN2BAS gene cluster reported in melanoma susceptible
      families, the deletion detected in the two sisters is peculiar for its de novo
      origin and for its extension, as it represents the largest constitutive deletion
      at 9p21.3 region identified so far.In addition, the two studied cases add to
      other evidence indicating association of melanoma with exposure to ionizing
      radiation and with second neoplasm after childhood cancer. Melanoma should be
      considered in the monitoring of pigmented lesions in young cancer patients.

PMID- 24884916
TI  - Population correlates of circulating mercury levels in Korean adults: the Korea
      National Health and Nutrition Examination Survey IV.
AB  - BACKGROUND: Prior studies focused on bioaccumulation of mercury (Hg) and on
      large, long-lived fish species as the major environmental source of Hg, but
      little is known about consumption of small-sized fish or about non-dietary
      determinants of circulating Hg levels. The purpose of this study was to evaluate
      whole blood mercury concentration (WBHg) and its major dietary and non-dietary
      correlates in Korean adults. METHODS: We analyzed cross-sectional data from 3,972
      (male = 1,994; female = 1,978) participants who completed the Korean National
      Health and Nutrition Examination Survey IV, 2008 to 2009. Relevant factors
      included diet, geographic location of residence, demographics, and lifestyle.
      WBHg concentration was measured using cold-vapor atomic absorption spectrometry.
      Multivariable linear models assessed independent correlates of dietary and non
      dietary factors for WBHg levels. RESULTS: Median levels of WBHg were 5.1 MUg/L in
      men and 3.7 MUg/L in women. Higher levels of fish/shellfish intake were
      associated with higher levels of WBHg. Higher consumption of small-sized fish was
      linked to higher levels of WBHg. Non-dietary predictors of higher WBHg were being
      male, greater alcohol consumption, higher income and education,
      overweight/obesity, increasing age, and living in the southeast region.
      CONCLUSIONS: Both dietary and non-dietary factors were associated with WBHg
      levels in the Korean population. There is significant geographic variation in
      WBHg levels; residents living in the mid-south have higher WBHg levels. We
      speculate that uncontrolled geographic characteristics, such as local soil/water
      content and specific dietary habits are involved.

PMID- 24884917
TI  - Sensory neuronopathy complicating systemic lupus erythematosus: a case report.
AB  - INTRODUCTION: Systemic lupus erythematosus is a multi-system connective tissue
      disorder. Peripheral neuropathy is a known and underestimated complication in
      systemic lupus erythematosus. Ganglionopathy manifests when neuronal cell bodies
      in the dorsal root ganglion are involved. Autoimmune disorders are a known
      etiology, with systemic lupus erythematosus being a rare cause. CASE
      PRESENTATION: A 32-year-old South Asian woman presented with oral ulceration
      involving her lips following initiation of treatment for a febrile illness
      associated with dysuria. She had a history of progressively worsening numbness
      over a period of 4 months involving both the upper and lower limbs symmetrically
      while sparing the trunk. Her vibration sense was impaired, and her reflexes were
      diminished. For the past 4 years, she had had a bilateral, symmetrical, non
      deforming arthritis involving the upper and lower limbs. Her anti-nuclear
      antibody and anti-double-stranded deoxyribonucleic acid status were positive.
      Although her anti-Ro antibodies were positive, she did not have clinical features
      suggestive of Sjogren syndrome. Nerve conduction studies revealed sensory
      neuronopathy. A diagnosis of systemic lupus erythematosus complicated by sensory
      neuronopathy was made. Treatment with intravenous immunoglobulin resulted in
      clinical and electrophysiological improvement. CONCLUSION: Peripheral neuropathy
      in systemic lupus erythematosus can, by itself, be a disabling feature. Nerve
      conduction studies should be considered when relevant. Neuropathy in systemic
      lupus erythematosus should be given greater recognition, and rarer forms of
      presentation should be entertained in the differential diagnosis when the
      clinical picture is atypical. Intravenous immunoglobulin may have role in
      treatment of sensory neuronopathy in systemic lupus erythematosus.

PMID- 24884918
TI  - Improving photodynamic inactivation of bacteria in dentistry: highly effective
      and fast killing of oral key pathogens with novel tooth-colored type-II
      photosensitizers.
AB  - Increasing antibiotic resistances in microorganisms create serious problems in
      public health. This demands alternative approaches for killing pathogens to
      supplement standard treatment methods. Photodynamic inactivation of bacteria
      (PIB) uses light activated photosensitizers (PS) to generate reactive oxygen
      species immediately upon illumination, inducing lethal phototoxicity. Positively
      charged phenalen-1-one derivatives are a new generation of PS for light-mediated
      killing of pathogens with outstanding singlet oxygen quantum yield PhiDelta of
      >97%. Upon irradiation with a standard photopolymerizer light (bluephase C8, 1260
      +/- 50 mW/cm(2)) the PS showed high activity against the oral key pathogens
      Enterococcus faecalis, Actinomyces naeslundii, Streptococcus mutans, and
      Aggregatibacter actinomycetemcomitans. At a concentration of 10 MUM, a maximum
      efficacy of more than 6 log10 steps (>= 99.9999%) of bacteria killing is reached
      in less than 1 min (light dose 50 J/cm(2)) after one single treatment. The
      pyridinium substituent as positively charged moiety is especially advantageous
      for antimicrobial action.

PMID- 24884919
TI  - Care-seeking and appropriate treatment for childhood acute respiratory illness:
      an analysis of Demographic and Health Survey and Multiple Indicators Cluster
      Survey datasets for high-mortality countries.
AB  - BACKGROUND: Acute lower respiratory illness (ALRI) is a major global cause of
      morbidity and mortality among children under 5. Antibiotic treatment for ALRI is
      inexpensive and decreases case fatality, but care-seeking patterns and
      appropriate treatment vary widely across countries. This study sought to examine
      patterns of appropriate treatment and estimate the burden of cases of untreated
      ALRI in high mortality countries. METHODS: This study used cross-sectional survey
      data from the Phase 5/Phase 6 DHS and MIC3/MICS4 for 39 countries. We analyzed
      care-seeking patterns and antibiotic treatment based on country-level trends, and
      estimated the burden of untreated cases using country-level predictors in a
      general linear model. RESULTS: According to this analysis, over 66 million
      children were not treated with antibiotics for ALRI in 2010. Overall, African
      countries had a lower proportion of mothers who sought care for a recent episode
      of ALRI (41% to 86%) relative to Asian countries (75% to 87%). Seeking any care
      for ALRI was inversely related to seeking public sector care. Treatment with
      antibiotics ranged from 8% in Nepal to 87% in Jordan, and was significantly
      associated with urban residence. CONCLUSIONS: Untreated ALRI remains a
      substantial problem in high mortality countries. In Asia, the large population
      numbers lead to a high burden of children with untreated ALRI. In Africa, care
      seeking behaviors and access to care issues may lead to missed opportunities to
      treat children with antibiotics.

PMID- 24884920
TI  - Developing attributes and attribute-levels for a discrete choice experiment on
      micro health insurance in rural Malawi.
AB  - BACKGROUND: Discrete choice experiments (DCEs) are attribute-driven experimental
      techniques used to elicit stakeholders' preferences to support the design and
      implementation of policy interventions. The validity of a DCE, therefore, depends
      on the appropriate specification of the attributes and their levels. There have
      been recent calls for greater rigor in implementing and reporting on the
      processes of developing attributes and attribute-levels for discrete choice
      experiments (DCEs). This paper responds to such calls by carefully reporting a
      systematic process of developing micro health insurance attributes and attribute
      levels for the design of a DCE in rural Malawi. METHODS: Conceptual attributes
      and attribute-levels were initially derived from a literature review which
      informed the design of qualitative data collection tools to identify context
      specific attributes and attribute-levels. Qualitative data was collected in
      August-September 2012 from 12 focus group discussions with community residents
      and 8 in-depth interviews with health workers. All participants were selected
      according to stratified purposive sampling. The material was tape-recorded, fully
      transcribed, and coded by three researchers to identify context-specific
      attributes and attribute-levels. Expert opinion was used to scale down the
      attributes and levels. A pilot study confirmed the appropriateness of the
      selected attributes and levels for a DCE. RESULTS: First, a consensus, emerging
      from an individual level analysis of the qualitative transcripts, identified 10
      candidate attributes. Levels were assigned to all attributes based on data from
      transcripts and knowledge of the Malawian context, derived from literature.
      Second, through further discussions with experts, four attributes were discarded
      based on multiple criteria. The 6 remaining attributes were: premium level, unit
      of enrollment, management structure, health service benefit package,
      transportation coverage and copayment levels. A final step of revision and
      piloting confirmed that the retained attributes satisfied the credibility
      criteria of DCE attributes. CONCLUSION: This detailed description makes our
      attribute development process transparent, and provides the reader with a basis
      to assess the rigor of this stage of constructing the DCE. This paper contributes
      empirical evidence to the limited methodological literature on attributes and
      levels development for DCE, thereby providing further empirical guidance on the
      matter, specifically within rural communities of low- and middle-income
      countries.

PMID- 24884921
TI  - Left ventricular support adjustment to aortic valve opening with analysis of
      exercise capacity.
AB  - BACKGROUND: LVAD speed adjustment according to a functioning aortic valve has
      hypothetic advantages but could lead to submaximal support. The consequences of
      an open aortic valve policy on exercise capacity and hemodynamics have not yet
      been investigated systematically. METHODS: Ambulatory patients under LVAD support
      (INCOR(r), Berlin Heart, mean support time 465 +/- 257 days, average flow 4.0 +/-
      0.3 L/min) adjusted to maintain a near normal aortic valve function underwent
      maximal cardiopulmonary exercise testing (CPET) and right heart catheterization
      (RHC) at rest and during constant work rate exercise (20 Watt). RESULTS: Although
      patients (n = 8, mean age 45 +/- 13 years) were in NYHA class 2, maximum work
      load and peak oxygen uptake on CPET were markedly reduced with 69 +/- 13 Watts
      (35% predicted) and 12 +/- 2 mL/min/kg (38% predicted), respectively. All
      patients showed a typical cardiac limitation pattern and severe ventilatory
      inefficiency with a slope of ventilation to carbon dioxide output of 42 +/- 12.
      On RHC, patients showed an exercise-induced increase of mean pulmonary artery
      pressure (from 16 +/- 2.4 to 27 +/- 2.8 mmHg, p < 0.001), pulmonary artery wedge
      pressure (from 9 +/- 3.3 to 17 +/- 5.3 mmHg, p = 0.01), and cardiac output (from
      4.7 +/- 0.5 to 6.2 +/- 1.0 L/min, p = 0.008) with a corresponding slight increase
      of pulmonary vascular resistance (from 117 +/- 35.4 to 125 +/- 35.1 dyn*sec*cm-5,
      p = 0.58) and a decrease of mixed venous oxygen saturation (from 58 +/- 6 to 32
      +/- 9%, p < 0.001). CONCLUSION: An open aortic valve strategy leads to impaired
      exercise capacity and hemodynamics, which is not reflected by NYHA-class. Unknown
      compensatory mechanisms can be suspected. Further studies comparing higher vs.
      lower support are needed for optimization of LVAD adjustment strategies.

PMID- 24884923
TI  - The 9th annual INDUS-EM 2013 Emergency Medicine Summit, "Principles, Practices,
      and Patients," a level one international meeting, Kerala University of Health
      Sciences and Jubilee Mission Medical College and Research Institute, Thrissur,
      Kerala, India, October 23-27, 2013.
AB  - INDUS-EM is India's only level one conference imparting and exchanging quality
      knowledge in acute care. Specifically, in general and specialized emergency care
      and training in trauma, burns, cardiac, stroke, environmental and disaster
      medicine. It provides a series of exchanges regarding academic development and
      implementation of training tools related to developing future academic faculty
      and residents in Emergency Medicine in India. The INDUS-EM leadership and board
      of directors invited scholars from multiple institutions to participate in this
      advanced educational symposium that was held in Thrissur, Kerala in October 2013.

PMID- 24884922
TI  - Autoimmune pancreatitis can develop into chronic pancreatitis.
AB  - Autoimmune pancreatitis (AIP) has been recognized as a distinct type of
      pancreatitis that is possibly caused by autoimmune mechanisms. AIP is
      characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in
      affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid
      therapy and results in the amelioration of clinical findings. However, the long
      term prognosis and outcome of AIP remain unclear. We have proposed a working
      hypothesis that AIP can develop into ordinary chronic pancreatitis resembling
      alcoholic pancreatitis over a long-term course based on several clinical
      findings, most notably frequent pancreatic stone formation. In this review
      article, we describe a series of study results to confirm our hypothesis and
      clarify that: 1) pancreatic calcification in AIP is closely associated with
      disease recurrence; 2) advanced stage AIP might have earlier been included in
      ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience
      pancreatic stone formation over a long-term course, for which a primary risk
      factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of
      AIP patients progress to confirmed chronic pancreatitis according to the revised
      Japanese Clinical Diagnostic Criteria, with independent risk factors being
      pancreatic head swelling and non-narrowing of the pancreatic body duct. 

PMID- 24884924
TI  - Prednisolone has a positive effect on the kidney but not on the liver of brain
      dead rats: a potencial role in complement activation.
AB  - BACKGROUND: Contradictory evidence has been published on the effects of steroid
      treatments on the outcomes of kidney and liver transplantation from brain dead
      (BD) donors. Our study aimed to evaluate this disparity by investigating the
      effect of prednisolone administration on BD rats. METHODS: BD induction was
      performed in ventilated rats by inflating a Fogarty catheter placed in the
      epidural space. Prednisolone (22.5 mg/kg) was administered 30 min prior to BD
      induction. After four hours of determination of BD: serum, kidney and liver
      tissues samples were collected and stored. RT-qPCR, routine biochemistry and
      immunohistochemistry were performed. RESULTS: Prednisolone treatment reduced
      circulating IL-6 and creatinine plasma levels but not serum AST, ALT or LDH.
      Polymorphonuclear influx assessed by histology, and inflammatory gene expression
      were reduced in the kidney and liver. However, complement component 3 (C3)
      expression was decreased in kidney but not in liver. Gene expression of HSP-70, a
      cytoprotective protein, was down-regulated in the liver after treatment.
      CONCLUSIONS: This study shows that prednisolone decreases inflammation and
      improves renal function, whilst not reducing liver injury. The persistence of
      complement activation and the negative effect on protective cellular mechanisms
      in the liver may explain the disparity between the effects of prednisolone on the
      kidney and liver of BD rats. The difference in the molecular and cellular
      responses to prednisolone administration may explain the contradictory evidence
      of the effects of prednisolone on different organ types from brain dead organ
      donors.

PMID- 24884925
TI  - Antigenic and 3D structural characterization of soluble X4 and hybrid X4-R5 HIV-1
      Env trimers.
AB  - BACKGROUND: HIV-1 is decorated with trimeric glycoprotein spikes that enable
      infection by engaging CD4 and a chemokine coreceptor, either CCR5 or CXCR4. The
      variable loop 3 (V3) of the HIV-1 envelope protein (Env) is the main determinant
      for coreceptor usage. The predominant CCR5 using (R5) HIV-1 Env has been
      intensively studied in function and structure, whereas the trimeric architecture
      of the less frequent, but more cytopathic CXCR4 using (X4) HIV-1 Env is largely
      unknown, as are the consequences of sequence changes in and near V3 on
      antigenicity and trimeric Env structure. RESULTS: Soluble trimeric gp140 Env
      constructs were used as immunogenic mimics of the native spikes to analyze their
      antigenic properties in the context of their overall 3D structure. We generated
      soluble, uncleaved, gp140 trimers from a prototypic T-cell line-adapted (TCLA) X4
      HIV-1 strain (NL4-3) and a hybrid (NL4-3/ADA), in which the V3 spanning region
      was substituted with that from the primary R5 isolate ADA. Compared to an ADA
      (R5) gp140, the NL4-3 (X4) construct revealed an overall higher antibody
      accessibility, which was most pronounced for the CD4 binding site (CD4bs), but
      also observed for mAbs against CD4 induced (CD4i) epitopes and gp41 mAbs. V3 mAbs
      showed significant binding differences to the three constructs, which were
      refined by SPR analysis. Of interest, the NL4-3/ADA construct with the hybrid NL4
      3/ADA CD4bs showed impaired CD4 and CD4bs mAb reactivity despite the presence of
      the essential elements of the CD4bs epitope. We obtained 3D reconstructions of
      the NL4-3 and the NL4-3/ADA gp140 trimers via electron microscopy and single
      particle analysis, which indicates that both constructs inherit a propeller-like
      architecture. The first 3D reconstruction of an Env construct from an X4 TCLA HIV
      1 strain reveals an open conformation, in contrast to recently published more
      closed structures from R5 Env. Exchanging the X4 V3 spanning region for that of
      R5 ADA did not alter the open Env architecture as deduced from its very similar
      3D reconstruction. CONCLUSIONS: 3D EM analysis showed an apparent open trimer
      configuration of X4 NL4-3 gp140 that is not modified by exchanging the V3
      spanning region for R5 ADA.

PMID- 24884926
TI  - Therapeutic potential of a gamma-secretase inhibitor for hearing restoration in a
      guinea pig model with noise-induced hearing loss.
AB  - BACKGROUND: Notch signaling plays a crucial role in the fate determination of
      cochlear progenitor cells, hair cells, and supporting cells in the developing
      cochlea. Recent studies have demonstrated the temporal activation of Notch
      signaling in damaged mature cochleae, and have demonstrated the induction of new
      hair cells by pharmacologically inhibiting Notch signaling. The present study
      aimed to illustrate the feasibility of pharmacologically inhibiting Notch
      signaling by using a gamma-secretase inhibitor for treating sensorineural hearing
      loss. RESULTS: The effect of the sustained local delivery of MDL28170, a gamma
      secretase inhibitor, on hearing and hair cell induction was tested in a guinea
      pig model with noise-induced hearing loss. MDL28170 was directly delivered into
      the cochlear fluids via a micro-osmotic pump. Drug application was initiated 7
      days after noise exposure. Measurements of auditory brainstem responses revealed
      better hearing in the MDL28170-treated animals than in the vehicle controls.
      Histological analysis demonstrated a higher number of outer hair cells in the
      MDL28170-treated cochleae than the vehicle-treated cochleae. CONCLUSION: These
      findings strongly suggest that local sustained delivery of a gamma-secretase
      inhibitor into the cochlea could be a novel strategy for treating acute hearing
      loss that is refractory to conventional treatment.

PMID- 24884927
TI  - Multi-population genomic prediction using a multi-task Bayesian learning model.
AB  - BACKGROUND: Genomic prediction in multiple populations can be viewed as a multi
      task learning problem where tasks are to derive prediction equations for each
      population and multi-task learning property can be improved by sharing
      information across populations. The goal of this study was to develop a multi
      task Bayesian learning model for multi-population genomic prediction with a
      strategy to effectively share information across populations. Simulation studies
      and real data from Holstein and Ayrshire dairy breeds with phenotypes on five
      milk production traits were used to evaluate the proposed multi-task Bayesian
      learning model and compare with a single-task model and a simple data pooling
      method. RESULTS: A multi-task Bayesian learning model was proposed for multi
      population genomic prediction. Information was shared across populations through
      a common set of latent indicator variables while SNP effects were allowed to vary
      in different populations. Both simulation studies and real data analysis showed
      the effectiveness of the multi-task model in improving genomic prediction
      accuracy for the smaller Ayshire breed. Simulation studies suggested that the
      multi-task model was most effective when the number of QTL was small (n = 20),
      with an increase of accuracy by up to 0.09 when QTL effects were lowly correlated
      between two populations (rho = 0.2), and up to 0.16 when QTL effects were highly
      correlated (rho = 0.8). When QTL genotypes were included for training and
      validation, the improvements were 0.16 and 0.22, respectively, for scenarios of
      the low and high correlation of QTL effects between two populations. When the
      number of QTL was large (n = 200), improvement was small with a maximum of 0.02
      when QTL genotypes were not included for genomic prediction. Reduction in
      accuracy was observed for the simple pooling method when the number of QTL was
      small and correlation of QTL effects between the two populations was low. For the
      real data, the multi-task model achieved an increase of accuracy between 0 and
      0.07 in the Ayrshire validation set when 28,206 SNPs were used, while the simple
      data pooling method resulted in a reduction of accuracy for all traits except for
      protein percentage. When 246,668 SNPs were used, the accuracy achieved from the
      multi-task model increased by 0 to 0.03, while using the pooling method resulted
      in a reduction of accuracy by 0.01 to 0.09. In the Holstein population, the three
      methods had similar performance. CONCLUSIONS: Results in this study suggest that
      the proposed multi-task Bayesian learning model for multi-population genomic
      prediction is effective and has the potential to improve the accuracy of genomic
      prediction.

PMID- 24884928
TI  - Associations between indicators of nitrosative stress and levels of soluble HLA
      I, CD95 molecules in patients with COPD.
AB  - At the present stage of study of chronic obstructive pulmonary disease (COPD) one
      of the problem is the definition of new criteria for the topical and systemic
      chronic inflammation of this disease. The aim of the research was to study the
      concentration of nitric oxide metabolites, the level of soluble human leukocyte
      antigens class I (sHLA-I) and of soluble CD95 molecules (sCD95) in the serum of
      blood and exhaled breath condensate (EBC) in patients with exacerbation of COPD.
      We investigated 49 moderate-to-severe COPD patients with exacerbation, and 21
      healthy nonsmokers. The concentration of sHLA-I and sCD95 molecules was studied
      in serum and in EBC using the ELISA method. The nitrosative stress was evaluated
      by the measurement of NO2(-) levels in the serum and the concentration of
      SigmaNO2(2)/NO3(2) in the EBC. Exacerbation of COPD is associated with increasing
      concentrations of NO2(2) in the serum and of the levels of SigmaNO2(2)/NO3(2) in
      the EBC, together with the changing concentration of sHLA-I and sCD95 molecules
      in the both biological liquid. An association was discovered between the
      exacerbation of COPD and the indicators of nitrosative stress, the parameters of
      lung function and the concentration of sHLA-I, sCD95 molecules. The findings
      suggest a pathogenetic role of nitrosative stress and of soluble molecules of HLA
      I and CD95 in the progression of COPD. The studied markers can be used as
      predictors of unfavourable prognoses of COPD and as quantitative criteria in the
      diagnosis of exacerbation of moderate-to-severe COPD.

PMID- 24884929
TI  - Increasing late stage colorectal cancer and rectal cancer mortality demonstrates
      the need for screening: a population based study in Ireland, 1994-2010.
AB  - BACKGROUND: This paper describes trends in colorectal cancer incidence, survival
      and mortality from 1994 to 2010 in Ireland prior to the introduction of
      population-based screening. METHODS: We examined incidence (National Cancer
      Registry Ireland (NCRI) and mortality (Central Statistics Office) from 1994 to
      2010. Age standardised rates (ASR) for incidence and mortality have been
      calculated, weighted by the European standard population. Annual percentage
      change was calculated in addition to testing for linear trends in treatment and
      case fraction of early and late stage disease. Relative survival was calculated
      considering deaths from all causes. RESULTS: The colorectal cancer ASR was 63.7
      per 100,000 in males and 38.7 per 100,000 in females in 2010. There was little
      change in the ASR over time in either sex, or when colon and rectal cancers were
      considered separately; however the number of incident cancers increased
      significantly during 1994-2010 (1752 to 2298). The case fractions of late stage
      (III/IV) colon and rectal cancers rose significantly over time. One and 5 year
      relative survival improved for both sexes between the periods 1994-2008.
      Colorectal cancer mortality ASRs decreased annually from 1994-2009 by 1.8% (95%
      CI -2.2, -1.4). Rectal cancer mortality ASRs rose annually by 2.4% (95% CI 1.1,
      3.6) and 2.8% (95% CI 1.2, 4.4) in males and females respectively. CONCLUSIONS:
      Increases in late-stage disease and rectal cancer mortality demonstrate an urgent
      need for colorectal cancer screening. However, the narrow age range at which
      screening is initially being rolled-out in Ireland means that the full potential
      for reductions in late-stage cancers and incidence and mortality are unlikely to
      be achieved. While it is possible that the observed increase in rectal cancer
      mortality may be partly an artefact of cause of death misclassification, it could
      also be explained by variations in treatment and adherence to best practice
      guidelines; further investigation is warranted.

PMID- 24884930
TI  - 'Choice, culture and confidence': key findings from the 2012 having a baby in
      Queensland Aboriginal and Torres Strait Islander survey.
AB  - BACKGROUND: To describe the maternity care experiences of Aboriginal and/or
      Torres Strait Islander women in Queensland, Australia and to identify areas for
      policy and practice improvements. METHODS: A culturally-tailored survey
      requesting both quantitative and qualitative information was completed by
      respondents either independently (online or in hard copy) or with the assistance
      of a trained peer-interviewer. Data were analysed using descriptive statistics
      and thematic analysis.Eligible women were over 16 years of age, identified as
      Aboriginal and/or Torres Strait Islander, resided in Queensland, and had a live,
      singleton birth between the first of July 2011 and the first of July 2012.
      RESULTS: 187 women of 207 respondents were included in analyses. Women reported
      high rates of stressful life events in pregnancy, low levels of choice in place
      of birth and model of care and limited options to carry out cultural practices.
      High levels of confidence in parenting were also reported. Women were less likely
      to report being treated with kindness, understanding and respect by maternity
      care staff than women answering a similar mainstream survey. CONCLUSIONS:
      Aboriginal and Torres Strait Islander women have additional needs to mainstream
      Australian women. This study identified a number of recommendations to improve
      services including the need to enhance the cultural competence of maternity
      services; increase access to continuity of midwifery care models, facilitate more
      choices in care, work with the strengths of Aboriginal and Torres Strait Islander
      women, families and communities, and engage women in the design and delivery of
      care.

PMID- 24884931
TI  - The DREEM, part 1: measurement of the educational environment in an osteopathy
      teaching program.
AB  - BACKGROUND: Measurement of the educational environment has become more common in
      health professional education programs. Information gained from these
      investigations can be used to implement and measure changes to the curricula,
      educational delivery and the physical environment. A number of questionnaires
      exist to measure the educational environment, and the most commonly utilised of
      these is the Dundee Ready Educational Environment Measure (DREEM). METHODS: The
      DREEM was administered to students in all year levels of the osteopathy program
      at Victoria University (VU), Melbourne, Australia. Students also completed a
      demographic survey. Inferential and correlational statistics were employed to
      investigate the educational environment based on the scores obtained from the
      DREEM. RESULTS: A response rate of 90% was achieved. The mean total DREEM score
      was 135.37 (+/- 19.33) with the scores ranging from 72 to 179. Some subscales and
      items demonstrated differences for gender, clinical phase, age and whether the
      student was in receipt of a government allowance. CONCLUSIONS: There are a number
      of areas in the program that are performing well, and some aspects that could be
      improved. Overall students rated the VU osteopathy program as more positive than
      negative. The information obtained in the present study has identified areas for
      improvement and will enable the program leaders to facilitate changes. It will
      also provide other educational institutions with data on which they can make
      comparisons with their own programs.

PMID- 24884932
TI  - A cross-sectional analysis of symptom severity in adults with influenza and other
      acute respiratory illness in the outpatient setting.
AB  - BACKGROUND: Acute respiratory infections (ARIs) are common in outpatient
      practice, and the severity of symptoms contributes to the overall burden of
      illness. We examined the association between a subjective symptom severity score,
      demographic and clinical characteristics, and presence of laboratory-confirmed
      influenza among central Wisconsin adults who sought care for ARI during four
      influenza seasons. We hypothesized that adults with laboratory-confirmed
      influenza would rate their symptoms as more severe relative to adults without
      influenza, and vaccinated adults with influenza would rate symptoms as less
      severe than those who were not vaccinated. METHODS: Patients with acute
      respiratory illness, including feverishness or cough symptoms <= 7 days duration,
      were prospectively enrolled and tested for influenza by reverse transcription
      polymerase chain reaction (RT-PCR) during influenza seasons 2007-08 through 2010
      11. Perceived severity was self-rated during the enrollment interview for eight
      symptoms, on a scale of 0 (absent) to 3 (severe). Scores for each symptom were
      summed to generate a combined severity score ranging from 1 to 24 for each
      individual. The association between influenza test result and severity score was
      examined using linear regression. RESULTS: There were 2,374 individuals included
      in the analysis, including 324 with RT-PCR confirmed influenza. The mean symptom
      severity score was 12.3 (+/-4.1) points, and the most common symptoms were cough
      (92%), fatigue (91%), and nasal congestion (84%). In the final adjusted model,
      influenza infection was the strongest independent predictor of higher severity
      score, with a mean increase of 1.7 points compared to those who were influenza
      negative (p < 0.001). Among adults with influenza, the association between
      influenza vaccination and symptom severity was modified by age (p < 0.001). In
      adults >= 65 years old with RT-PCR confirmed influenza, symptom severity was 31%
      lower in those who were vaccinated as compared to those who were not vaccinated.
      CONCLUSIONS: Influenza is associated with more severe symptoms of acute
      respiratory illness. The association between influenza vaccination and reduced
      symptom severity in older adults should be confirmed and explored further in
      other populations and seasons.

PMID- 24884933
TI  - Rhabdomyomas and tuberous sclerosis complex: our experience in 33 cases.
AB  - BACKGROUND: Rhabdomyomas are the most common type of cardiac tumors in children.
      Anatomically, they can be considered as hamartomas. They are usually randomly
      diagnosed antenatally or postnatally sometimes presenting in the neonatal period
      with haemodynamic compromise or severe arrhythmias although most neonatal cases
      remain asymptomatic. Typically rhabdomyomas are multiple lesions and usually
      regress spontaneously but are often associated with tuberous sclerosis complex
      (TSC), an autosomal dominant multisystem disorder caused by mutations in either
      of the two genes, TSC1 or TSC2. Diagnosis of tuberous sclerosis is usually made
      on clinical grounds and eventually confirmed by a genetic test by searching for
      TSC genes mutations. METHODS: We report our experience on 33 cases affected with
      rhabdomyomas and diagnosed from January 1989 to December 2012, focusing on the
      cardiac outcome and on association with the signs of tuberous sclerosis complex.
      We performed echocardiography using initially a Philips Sonos 2500 with a 7,5/5
      probe and in the last 4 years a Philips IE33 with a S12-4 probe. We investigated
      the family history, brain, skin, kidney and retinal lesions, development of
      seizures, and neuropsychiatric disorders. RESULTS: At diagnosis we detected 205
      masses, mostly localized in interventricular septum, right ventricle and left
      ventricle. Only in 4 babies (12%) the presence of a mass caused a significant
      obstruction. A baby, with an enormous septal rhabdomyoma associated to multiple
      rhabdomyomas in both right and left ventricular walls died just after birth due
      to severe heart failure. During follow-up we observed a reduction of rhabdomyomas
      in terms of both number and size in all 32 surviving patients except in one
      child. Eight patients (24,2%) had an arrhythmia and in 2 of these cases
      rhabdomyomas led to Wolf-Parkinson-White Syndrome. For all patients the
      arrhythmia spontaneously totally disappeared or was reduced gradually. With
      regarding to association with tuberous sclerosis, we diagnosed tuberous sclerosis
      clinically in 31 babies (93,9%). CONCLUSION: Rhabdobyomas are tumors with
      favorable prognosis because they frequently do not cause symptoms and they often
      regress in numbers and size. Nevertheless, due to frequent association with
      tuberous sclerosis complex and the resulting neurological impairment, the
      prognosis can result unfavorable.

PMID- 24884934
TI  - The role of meal viscosity and oat beta-glucan characteristics in human appetite
      control: a randomized crossover trial.
AB  - BACKGROUND: Foods that enhance satiety can help consumers to resist environmental
      cues to eat, and improve the nutritional quality of their diets. Viscosity
      generated by oat beta-glucan, influences gastrointestinal mechanisms that mediate
      satiety. Differences in the source, processing treatments, and interactions with
      other constituents in the food matrix affect the amount, solubility, molecular
      weight, and structure of the beta-glucan in products, which in turn influences
      the viscosity. This study examined the effect of two types of oatmeal and an oat
      based ready-to-eat breakfast cereal (RTEC) on appetite, and assessed differences
      in meal viscosity and beta-glucan characteristics among the cereals. METHODS:
      Forty-eight individuals were enrolled in a randomized crossover trial. Subjects
      consumed isocaloric breakfast meals containing instant oatmeal (IO), old
      fashioned oatmeal (SO) or RTEC in random order at least a week apart. Each
      breakfast meal contained 218 kcal (150 kcal cereal, and 68 kcal milk) Visual
      analogue scales measuring appetite were completed before breakfast, and over four
      hours, following the meal. Starch digestion kinetics, meal viscosities, and beta
      glucan characteristics for each meal were determined. Appetite responses were
      analyzed by area under the curve. Mixed models were used to analyze response
      changes over time. RESULTS: IO increased fullness (p = 0.04), suppressed desire
      to eat (p = 0.01) and reduced prospective intake (p < 0.01) more than the RTEC
      over four hours, and consistently at the 60 minute time-point. SO reduced
      prospective intake (p = 0.04) more than the RTEC. Hunger scores were not
      significantly different except that IO reduced hunger more than the RTEC at the
      60 minute time-point. IO and SO had higher beta-glucan content, molecular weight,
      gastric viscosity, and larger hydration spheres than the RTEC, and IO had greater
      viscosity after oral and initial gastric digestion (initial viscosity) than the
      RTEC. CONCLUSION: IO and SO improved appetite control over four hours compared to
      RTEC. Initial viscosity of oatmeal may be especially important for reducing
      appetite.

PMID- 24884935
TI  - Tandem keyhole foraminotomy in the treatment of cervical radiculopathy:
      retrospective review of 35 cases.
AB  - BACKGROUND: There has been no report regarding the results of two-level keyhole
      foraminotomy. The purpose of this study was to detail clinical outcomes following
      consecutive two-level cervical foraminotomy (tandem keyhole foraminotomy (TKF))
      in patients with radiculopathy. METHODS: The authors conducted a retrospective
      review of 35 cases involving patients treated by a single surgeon using TKF.
      Clinical symptoms, data of physical examinations, pathology and clinical outcomes
      were detailed and discussed about this surgical method. RESULTS: Patients
      consisted of cervical disc herniation (CDH) (19/35), cervical spondylotic
      radiculopathy (CSR) (13/35), and cervical spondylotic amyotrophy (CSA) (3/35).
      TKF was performed from C3 to C5 in 2 patients (6%), from C4 to C6 in 7 patients
      (20%), from C5 to C7 in 23 patients (66%), and from C6 to T1 in 3 patients (8%).
      The mean operative duration was 99.2 min (range, 72 to 168 min). The mean
      estimated blood loss was 55.8 g (range, 0 to 200 g). Radicular pain was relieved
      within 3 months in 88% (29/32) and in 97% (31/32) at final follow-up. Resolution
      of muscle weakness was recognized within 6 months after operation in all CSA
      cases. Sixty-six percent of patients showed a greater than 20% deficit in grip
      weakness on the affected side compared with the normal side. After pain was
      relieved, grip strength improved by more than 15%. CONCLUSIONS: TKF is a safe and
      highly effective procedure for patients with cervical radiculopathy and does not
      require invasive preoperative examinations. Further investigation is required to
      determine the effects of consecutive facetectomy.

PMID- 24884936
TI  - Development and validation of the Japanese version of the obsessive-compulsive
      inventory.
AB  - BACKGROUND: The Obsessive-Compulsive Inventory (OCI) was designed to evaluate the
      severity of obsessive-compulsive symptoms in both clinical and non-clinical
      samples. The aim of the study was to develop a Japanese version of this scale
      (OCI-J) and validate it in both non-clinical and clinical Japanese samples.
      FINDINGS: In Study 1, the OCI-J, the Maudsley Obsessional Compulsive Inventory
      (MOCI), and measures of anxiety and depression were administered to 150
      undergraduate students (non-clinical sample) in order to investigate the internal
      consistency and convergent validity of the OCI-J. Furthermore, 118 non-clinical
      participants completed the OCI-J after a 2-week interval to determine the test
      retest reliability. In Study 2, OCD participants (n = 35), anxiety control
      participants with panic disorder (n = 22), and healthy control participants (n =
      37) completed the OCI-J in order to test its clinical discrimination
      ability.Correlational analysis indicated moderate to high correlations between
      the subscales and total scores of the OCI-J and MOCI. In addition, the OCI-J and
      its subscales demonstrated satisfactory test-retest reliabilities. Finally, the
      OCI-J showed good clinical discrimination for patients with OCD from healthy and
      anxiety controls. CONCLUSIONS: The OCI-J is a valid and reliable instrument for
      measuring OCD symptoms in both clinical and non-clinical samples of Japanese.

PMID- 24884937
TI  - Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic
      lateral sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron
      disease leading to the death of affected individuals within years. The
      involvement of inflammation in the pathogenesis of neurodegenerative diseases,
      including ALS, is increasingly recognized but still not well understood. The aim
      of this study is to evaluate the levels of inflammation-related IL-1 family
      cytokines (IL-1beta, IL-18, IL-33, IL-37) and their endogenous inhibitors (IL
      1Ra, sIL-1R2, IL-18BP, sIL-1R4) in patients with sporadic ALS (sALS), METHODS:
      Sera were collected from 144 patients (125 patients were characterized by disease
      form, duration, and disability, using the revised ALS functional rating scale
      (ALSFRS-R) and from 40 matched controls. Cerebrospinal fluid (CSF) was collected
      from 54 patients with sALS and 65 patients with other non-infectious non
      oncogenic diseases as controls. Cytokines and inhibitors were measured by
      commercial ELISA. RESULTS: Among the IL-1 family cytokines tested total IL-18,
      its endogenous inhibitor IL-18BP, and the active form of the cytokine (free IL
      18) were significantly higher in the sALS sera than in controls. No correlation
      between these soluble mediators and different clinical forms of sALS or the
      clinical setting of the disease was found. IL-18BP was the only mediator
      detectable in the CSF of patients. CONCLUSIONS: Among the IL-1 family cytokines,
      only IL-18 correlates with this disease and may therefore have a pathological
      role in sALS. The increase of total IL-18 suggests the activation of IL-18
      cleaving inflammasome. Whether IL-18 upregulation in circulation of sALS patients
      is a consequence of inflammation or one of the causes of the pathology still
      needs to be addressed.

PMID- 24884938
TI  - Fungemia due to Lachancea fermentati: a case report.
AB  - BACKGROUND: Lachancea fermentati is an environmental yeast that is also used in
      the fermentation of alcoholic drinks. It has not previously been described as a
      human pathogen although the closely related yeast, Saccharomyces boulardii, can
      cause fungemia. Here we report a case of L. fermentati acting as a pathogen in a
      septic patient with cultures positive from blood, peritoneal fluid, bile, and
      sputum. CASE PRESENTATION: A 36 year-old Caucasian man was hospitalized with
      acute alcoholic hepatitis complicated by Escherichia coli spontaneous bacterial
      peritonitis. Three days after admission, he developed new fevers with sepsis
      requiring mechanical ventilation and vasopressor support. He was found to have a
      bowel perforation. Cultures from blood, peritoneal fluid, and sputum grew a
      difficult-to-identify yeast. Micafungin was started empirically. On hospital day
      43 the yeast was identified as L. fermentati with low minimum inhibitory
      concentrations (by Epsilometer test) to all antifungals tested. Micafungin was
      changed to fluconazole to complete a 3-month course of therapy. Serial peritoneal
      fluid cultures remained positive for 31 days. One year after his initial
      hospitalization the patient had ongoing cirrhosis but had recovered from
      fungemia. CONCLUSION: This case demonstrates the need for clinicians to consider
      host factors when interpreting culture results with normally non-pathogenic
      organisms. In this immunocompromised host L. fermentati caused disseminated
      disease. We believe his hobby of brewing alcohol led to colonization with L.
      fermentati, which then resulted in invasive disease when the opportunity arose.

PMID- 24884939
TI  - Comparing the cultivated cochlear cells derived from neonatal and adult mouse.
AB  - BACKGROUND: Previous reports showed the presence of limited numbers of stem cells
      in neonatal murine cochlear sensory epithelia and these cells are progressively
      lost during the postnatal development. The goal of this study was to investigate
      whether stem cells can be derived from mature mouse cochleae under suspension
      culture conditions, and to analyze the expression of the stem cell and inner ear
      progenitor cell markers in cells dissociated from neonatal and adult mouse organs
      of Corti. METHODS: Organs of Corti were dissected from postnatal day 1 (P1) or
      postnatal day 60 (P60) mouse. The dissociated cells were cultivated under
      suspension cultures conditions. Reverse transcription-polymerase chain reaction
      (RT-PCR) and immunocytochemistry were conducted for phenotype characterization.
      RESULTS: The number of cochlear stem cells (otospheres) yielded from P1 organ of
      Corti was significantly higher than that of the P60 organ of Corti. RT-PCR
      analyses showed that the stem markers, such as nanog, sox2, klf4, and nestin can
      be found to be distributed similarly in the cells derived from both of organisms,
      but the inner ear developmental/progenitor cell markers showed lower expression
      in P60 organ of Corti compared to P1. Immunocytochemistry results also revealed
      the evidence that P60 otospheres lacking of differentiation potential in vitro,
      which opposed to the strong differentiation potential of otospheres at P1 stage.
      CONCLUSIONS: Our findings suggest that the loss of numbers and features of stem
      cells in the adult organ of Corti is associated with the substantial down
      regulation of inner ear progenitor key-markers during maturation of the cells in
      organ of Corti.

PMID- 24884941
TI  - Human epidermal growth factor receptor 2-positive microinvasive breast carcinoma
      with a highly aggressive course: a case report.
AB  - BACKGROUND: Microinvasive ductal carcinoma in situ of the breast is a rare entity
      defined as ductal carcinoma in situ with invasive foci measuring no more than 1
      mm. In general, the outcome is excellent, similar to ductal carcinoma in situ. We
      report a patient with breast ductal carcinoma in situ with microinvasion who died
      eight months after diagnosis due to progression of the disease - liver
      metastases. This is the first report in the literature of such an aggressive
      course. CASE PRESENTATION: A 47-year-old Caucasian woman presented with
      mammographic-detected suspicious microcalcinations in an area of 8.6 x 6 cm. A
      radical mastectomy with a sentinel lymph node biopsy and immediate breast
      reconstruction with implant was performed. A histopathological report showed a
      massive high grade ductal carcinoma in situ, of the solid and comedo type. In one
      quadrant, some foci of microinvasions of less than 1 mm were present. Tumour
      margins were free. Isolated tumour cells were found in the sentinel lymph node.
      Hormone receptors were negative and human epidermal growth factor receptor-2
      status was not performed. The patient received no adjuvant systemic therapy.
      Eight months after the surgery, she died from hepatic failure without known
      breast cancer progression before. An autopsy revealed diffuse liver metastases
      with human epidermal growth factor receptor 2-positive, hormone receptor negative
      breast cancer. Dissemination to other organs was not proven. CONCLUSION: Our
      patient is a rare case of ductal carcinoma in situ with microinvasion that
      developed distant metastases very early. In case of multiple foci of
      microinvasion, besides radical local treatment we suggest considering adjuvant
      systemic treatment based on biological characteristics since tumour size alone
      does not predict the prognosis well.

PMID- 24884940
TI  - Prevalence of gastrointestinal stromal tumour (GIST) in the United Kingdom at
      different therapeutic lines: an epidemiologic model.
AB  - BACKGROUND: The prevalence of patients with gastrointestinal stromal tumourgst
      (GIST) who fail currently available treatments imatinib and sunitinib (third-line
      treatment-eligible GIST) is unknown, but is expected to be below an ultra-orphan
      disease threshold of 2/100,000 population used in England and Wales. Our study
      was designed to estimate the prevalence and absolute number of UK patients with
      unresectable/metastatic GIST at first-, second- and eventually third-line
      treatment. METHODS: Our open population model estimates the probability that the
      prevalence of UK third-line treatment-eligible GIST patients will remain under
      the ultra-orphan disease threshold. Model parameters for incidence, proportion of
      unresectable/metastatic disease and survival estimates for GIST patients were
      obtained from a targeted literature review and a UK cancer register. The
      robustness of the results was checked through differing scenarios taking extreme
      values of the input parameters. RESULTS: The base-case scenario estimated a
      prevalence of third-line treatment-eligible GIST of 1/100,000 and a prevalence
      count of 598 with a 99.9% likelihood of being below the ultra-orphan disease
      threshold. The extreme scenarios, one-way and probabilistic sensitivity analyses
      and threshold analysis confirmed the robustness of these results. CONCLUSIONS:
      The prevalence of third-line treatment-eligible GIST is very low and highly
      likely below the ultra-orphan disease threshold.

PMID- 24884942
TI  - Genetic test to stop smoking (GeTSS) trial protocol: randomised controlled trial
      of a genetic test (Respiragene) and Auckland formula to assess lung cancer risk.
AB  - BACKGROUND: A gene-based estimate of lung cancer risk in smokers has been shown
      to act as a smoking cessation motivator in hospital recruited subjects. The
      objective of this trial is to determine if this motivator is as effective in
      subjects recruited from an NHS primary care unit. METHOD/DESIGN: Subjects will be
      recruited by mailings using smoking entries on the GP electronic data-base (total
      practice population = 32,048) to identify smokers who may want to quit. Smoking
      cessation clinics based on medical centre premises will run for eight weeks.
      Clinics will be randomised to have the gene-based test for estimation of lung
      cancer risk or to act as controls groups. The primary endpoint will be smoking
      cessation at eight weeks and six months. Secondary outcomes will include ranking
      of the gene-based test with other smoking cessation motivators. DISCUSSION: The
      results will inform as to whether the gene-based test is both effective as
      motivator and acceptable to subjects recruited from primary care. TRIAL
      REGISTRATION: Registered with Clinical Trials.gov, REGISTRATION NUMBER:
      NCT01176383.

PMID- 24884943
TI  - Characteristics of adults involved in alcohol-related intimate partner violence:
      results from a nationally representative sample.
AB  - BACKGROUND: More than 12 million women and men are victims of partner violence
      each year. Although the health outcomes of partner violence have been well
      documented, we know very little about specific event-level characteristics that
      may provide implications for prevention and intervention of partner violence
      situations. Therefore, the purpose of this study is to evaluate substance abuse
      and dependence as risk factors for event-level alcohol-related intimate partner
      violence (IPV). METHODS: Data were derived from Wave II of the National
      Epidemiological Survey on Alcohol and Related Conditions (2004-2005). Eligible
      participants (N = 2,255) reported IPV the year before the survey. Negative
      binomial and ordinal regression methods were used to assess risk factors for
      alcohol use during IPV. RESULTS: Respondent PTSD was the only mental health
      diagnosis related to alcohol use during IPV (OR = 1.45). Marijuana use was
      related to respondents' use of alcohol during IPV (OR = 2.68). Respondents'
      meeting the criteria for alcohol abuse/dependence was strongly associated with
      respondent drinking (OR = 10.74) and partner drinking (OR = 2.89) during IPV.
      CONCLUSION: Results indicate that PTSD, marijuana use disorders, alcohol abuse
      and dependence are associated with more frequent alcohol use during IPV. In
      addition, it is important to consider that the patient who presents in emergency
      settings (e.g., hospitals or urgent care facilities) may not be immediately
      identifiable as the victim or the perpetrator of partner violence. Therefore,
      screening and intervention programs should probe to further assess the event
      level characteristics of partner violence situations to ensure the correct
      service referrals are made to prevent partner violence.

PMID- 24884944
TI  - Medical insurance policy organized by Chinese government and the health inequity
      of the elderly: longitudinal comparison based on effect of New Cooperative
      Medical Scheme on health of rural elderly in 22 provinces and cities.
AB  - BACKGROUND: The alarming progression of the aging trend in China attracts much
      attention in the country and abroad. In 2003, the Chinese central government
      launched the New Cooperative Medical Scheme (NCMS) to resolve the inequity
      problem of health in regions with inadequate infrastructure and relative poverty.
      The rural elderly are the main beneficiaries of this policy; the improvement of
      their health through the medical insurance policy require exploration. METHODS:
      This study used data obtained from the Chinese Longitudinal Healthy Longevity
      Survey (CLHLS) conducted in 2005 and 2008. Elderly people living in rural areas
      and aged 60 and above were screened for the investigation. A total of 8658 and
      9904 elderly people were selected from 2005 and 2008, respectively. By
      establishing models and employing multi-logistic analysis, stereotype logistic
      analysis, we examined the effect of NCMS organized by Chinese government on three
      domains of the health of the rural elderly. RESULTS: A total of 948 and 6361
      elderly people participated in NCMS in 2005 (n = 8658) and 2008 (n = 9904),
      respectively. With regard to the independent variables, the number of
      participants in NCMS increased, whereas province distribution, gender, and years
      of education only slightly changed. As for the dependent variables, the rural
      elderly in 2005 had poor general health but good psychological health.
      Differences were found between different moods. Old people who engage in much
      outdoor activity can take care of themselves. After three-year promotion of NCMS,
      the differences between 2005 and 2008 indicate that the physical function of the
      rural elderly worsen, whereas the general health and psychological health
      improves. CONCLUSIONS: (1) In the 2005 data and 2008 data, result shows that NCMS
      participation can promote the self-rated quality and health change of the
      elderly. (2) After three years, the alleviation effect on anxiety and loneliness
      changed from insignificant to significant. Participants in NCMS have a stronger
      sense of uselessness, which weakens with time. (3 )NCMS participation passes the
      significance test in "outdoor activities" and "pick a book up from the floor"
      model. Elderly participants indicated higher frequencies of outdoor activities.

PMID- 24884945
TI  - Internal translation of the connexin 43 transcript.
AB  - BACKGROUND: Connexin 43 (Cx43), the most widely expressed gap junction protein,
      is associated with a number of physiological and pathological conditions. Many
      functions of Cx43 have been shown to be independent of gap junction formation and
      only require the expression of Cx43 C-terminal fragments. Recent evidence
      demonstrated that naturally occurring C-terminal isoforms can be generated via
      internal translation. FINDINGS: Here, we confirm that C-terminal domains of Cx43,
      particularly the major 20-kDa isoform, can be independently generated and
      regulated by internal translation of the same single GJA1 gene transcript that
      encodes full-length Cx43. Through direct RNA transfection experiments, we provide
      evidence that internal translation is not due to a bona fide cap-independent IRES
      mediated mechanism, as upstream ribosomal scanning or translation is required. In
      addition to the mTOR pathway, we show for the first time, using both inhibitors
      and cells from knockout mice, that the Mnk1/2 pathway regulates the translation
      of the main 20-kDa isoform. CONCLUSIONS: Internal translation of the Cx43
      transcript occurs but is not cap-independent and requires translation upstream of
      the internal start codon. In addition to the PI3K/AKT/mTOR pathway, the major 20
      kDa isoform is regulated by the Mnk1/2 pathway. Our results have major
      implications for past and future studies describing gap junction-independent
      functions of Cx43 in cancer and other pathological conditions. This study
      provides further clues to the signalling pathways that regulate internal mRNA
      translation, an emerging mechanism that allows for increased protein diversity
      and functional complexity from a single mRNA transcript.

PMID- 24884946
TI  - A novel quadruplex real-time PCR method for simultaneous detection of Cry2Ae and
      two genetically modified cotton events (GHB119 and T304-40).
AB  - BACKGROUND: To date, over 150 genetically modified (GM) crops are widely
      cultivated. To comply with regulations developed for genetically modified
      organisms (GMOs), including labeling policies, many detection methods for GMO
      identification and quantification have been developed. RESULTS: To detect the
      entrance and exit of unauthorized GM crop events in China, we developed a novel
      quadruplex real-time PCR method for simultaneous detection and quantification of
      GM cotton events GHB119 and T304-40 in cotton-derived products (based on the 5'
      flanking sequence) and the insect-resistance gene Cry2Ae. The limit of detection
      was 10 copies for GHB119 and Cry2Ae and 25 copies for T304-40. The limit of
      quantification was 25 copies for GHB119 and Cry2Ae and 50 copies for T304-40.
      Moreover, low bias and acceptable standard deviation and relative standard
      deviation values were obtained in quantification analysis of six blind samples
      containing different GHB119 and T304-40 ingredients. CONCLUSIONS: The developed
      quadruplex quantitative method could be used for quantitative detection of two GM
      cotton events (GHB119 and T304-40) and Cry2Ae gene ingredient in cotton derived
      products.

PMID- 24884947
TI  - HIV behavioural interventions targeted towards older adults: a systematic review.
AB  - BACKGROUND: The increasing number of people living with HIV aged 50 years and
      older has been recognised around the world yet non-pharmacologic HIV behavioural
      and cognitive interventions specifically targeted to older adults are limited.
      Evidence is needed to guide the response to this affected group. METHODS: We
      conducted a systematic review of the available published literature in MEDLINE,
      Embase and the Education Resources Information Center. A search strategy was
      defined with high sensitivity but low specificity to identify behavioural
      interventions with outcomes in the areas of treatment adherence, HIV testing
      uptake, increased HIV knowledge and uptake of prevention measures. Data from
      relevant articles were extracted into excel. RESULTS: Twelve articles were
      identified all of which originated from the Americas. Eight of the interventions
      were conducted among older adults living with HIV and four for HIV-negative older
      adults. Five studies included control groups. Of the included studies, four
      focused on general knowledge of HIV, three emphasised mental health and coping,
      two focused on reduced sexual risk behaviour, two on physical status and one on
      referral for care. Only four of the studies were randomised controlled trials and
      seven - including all of the studies among HIV-negative older adults - did not
      include controls at all. A few of the studies conducted statistical testing on
      small samples of 16 or 11 older adults making inference based on the results
      difficult. The most relevant study demonstrated that using telephone-based
      interventions can reduce risky sexual behaviour among older adults with control
      reporting 3.24 times (95% CI 1.79-5.85) as many occasions of unprotected sex at
      follow-up as participants. Overall however, few of the articles are sufficiently
      rigorous to suggest broad replication or to be considered representative and
      applicable in other settings. CONCLUSIONS: More evidence is needed on what
      interventions work among older adults to support prevention, adherence and
      testing. More methodological rigourised needed in the studies targeting older
      adults. Specifically, including control groups in all studies is needed as well
      as sufficient sample size to allow for statistical testing. Addition of specific
      bio-marker or validated behavioural or cognitive outcomes would also strengthen
      the studies.

PMID- 24884948
TI  - The challenge of recruiting patients into a placebo-controlled surgical trial.
AB  - BACKGROUND: Randomized placebo-controlled trials represent the gold standard in
      evaluating healthcare interventions but are rarely performed within orthopedics.
      Ethical concerns or well-known challenges in recruiting patients for surgical
      trials in general have been expressed and adding a placebo component only adds to
      this complexity. The purpose of this study was to report the challenges of
      recruiting patients into an orthopedic placebo-controlled surgical trial, to
      determine the number of patients needed to be screened and allocated in order to
      include one participant into the trial, and to identify reasons associated with
      participation in a placebo-controlled randomized surgical trial. METHODS: Data
      were extracted from an ongoing placebo-controlled randomized controlled trial
      (RCT) on meniscectomy versus placebo surgery. We calculated the number of
      patients needed to be screened in order to include the required number of
      participants into the RCT. Participating patients were asked about their
      rationale for joining the study and which type of information was most useful for
      deciding upon participation. RESULTS: A total of 476 patients entered the
      screening group, of which 190 patients fulfilled the inclusion and exclusion
      criteria. 102 patients declined to participate in the study due to various
      reasons and 46 were later excluded (no meniscus lesion on the magnetic resonance
      imaging scan or withdrawn consent). A total of 40 patients were finally included
      in the RCT. To include one patient into the RCT, 11.9 individuals needed to be
      screened. A total of 69% of participating patients considered the oral
      information to be the most important and the most common reason for participating
      was the contribution to research (90%). CONCLUSIONS: Patients are willing to
      participate in an orthopedic placebo-controlled surgical trial. Oral information
      given by the surgeon to the patient and the contribution to research are
      important aspects to enhance patient recruitment. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01264991, registered 21 December 2010.

PMID- 24884949
TI  - Manuka honey treatment of biofilms of Pseudomonas aeruginosa results in the
      emergence of isolates with increased honey resistance.
AB  - BACKGROUND: Medical grade manuka honeys are well known to be efficacious against
      Pseudomonas aeruginosa being bactericidal and inhibiting the development of
      biofilms; moreover manuka honey effectively kills P. aeruginosa embedded within
      an established biofilm. Sustained honey resistance has not been previously
      documented for planktonic or biofilm P. aeruginosa. METHODS: Minimum inhibitory
      concentrations for manuka honey and antibiotics were determined using broth micro
      dilution methods. Minimum biofilm eliminating concentrations (MBEC) and biofilm
      biomass were determined using the crystal violet method. Sub-culture used non
      selective media and the grid-plate method. RESULTS: When honey treated biofilm
      biomass of two strains of P. aeruginosa (reference strain ATCC 9027 and the
      clinical isolate 867) were sub-cultured onto non-selective media isolates emerged
      that exhibited reduced susceptibility to manuka honey. Significantly, this
      characteristic was sustained with repeated sub-culture onto non-selective media
      resulting in increased minimum inhibitory concentrations (MIC) of between 5-7%
      (w/v) and increased minimum biofilm eliminating concentrations (MBEC) of up to
      15% (w/v). Interestingly the resistant isolates showed reduced susceptibility to
      antibiotic treatment with rifampicin and imipenem as well as being more prolific
      biofilm-formers than the progenitor strains. CONCLUSIONS: P. aeruginosa biofilms
      treated with manuka honey equivalent to the MBEC harbour slow growing, viable
      persistor organisms that exhibit sustained, increased resistance to manuka honey
      and antibiotic treatment, suggesting a shared mechanism of resistance. This sheds
      new light on the propensity for biofilm embedded organisms to resist honey
      treatment and become persistor organisms that are tolerant to other antimicrobial
      therapies.

PMID- 24884950
TI  - Towards the PCR-based identification of Palaearctic Culicoides biting midges
      (Diptera: Ceratopogonidae): results from an international ring trial targeting
      four species of the subgenus Avaritia.
AB  - BACKGROUND: Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) are
      biological vectors of internationally important arboviruses. To understand the
      role of Culicoides in the transmission of these viruses, it is essential to
      correctly identify the species involved. Within the western Palaearctic region,
      the main suspected vector species, C. obsoletus, C. scoticus, C. dewulfi and C.
      chiopterus, have similar wing patterns, which makes it difficult to separate and
      identify them correctly. METHODS: In this study, designed as an inter-laboratory
      ring trial with twelve partners from Europe and North Africa, we assess four PCR
      based assays which are used routinely to differentiate the four species of
      Culicoides listed above. The assays based on mitochondrial or ribosomal DNA or
      microarray hybridisation were tested using aliquots of Culicoides DNA (extracted
      using commercial kits), crude lysates of ground specimens and whole Culicoides
      (265 individuals), and non-Culicoides Ceratopogonidae (13 individuals) collected
      from across Europe. RESULTS: A total of 800 molecular assays were implemented.
      The in-house assays functioned effectively, although specificity and sensitivity
      varied according to the molecular marker and DNA extraction method used. The
      Obsoletus group specificity was overall high (95-99%) while the sensitivity
      varied greatly (59.6-100%). DNA extraction methods impacted the sensitivity of
      the assays as well as the type of sample used as template for the DNA extraction.
      CONCLUSIONS: The results are discussed in terms of current use of species
      diagnostic assays and the future development of molecular tools for the rapid
      differentiation of cryptic Culicoides species.

PMID- 24884951
TI  - The role of intimate partner violence and other health-related social factors on
      postpartum common mental disorders: a survey-based structural equation modeling
      analysis.
AB  - BACKGROUND: Although studies suggest the relevance of intimate partner violence
      (IPV) and other health-related social characteristics as risk factors for
      postpartum mental health, literature lacks evidence about how these are
      effectively connected. This study thus aims to explore how socio-economic
      position, maternal age, household and marital arrangements, general stressors,
      alcohol misuse and illicit drug abuse, and especially psychological and physical
      IPV relate in a framework leading to postpartum common mental disorder (CMD).
      METHODS: The study was carried out in five primary health care units of Rio de
      Janeiro, Brazil, and included 810 randomly selected mothers of children up to
      five postpartum months waiting for pediatric visits. The postulated pathways
      between exposures and outcome were based on literature evidence and were further
      examined using structural equation models. RESULTS: Direct pathways to postpartum
      CMD arose from a latent variable depicting socio-economic position, a general
      stressors score, and both IPV variables. Notably, the effect of psychological IPV
      on postpartum CMD ran partly through physical IPV. The effect of teenage
      pregnancy, conjugal instability and maternal burden apparently happens solely
      through substance use, be it alcohol misuse, illicit drug abuse or both in
      tandem. Moreover, the effect of the latter on CMD seems to be entirely mediated
      through both types of IPV. CONCLUSION: Although the theoretical model underlying
      the analysis still requires in-depth detailing, results of this study may have
      shed some light on the role of both psychological and physical IPV as part of an
      intricate network of events leading to postpartum CMD. Health initiatives may
      want to make use of this knowledge when designing preventive and intervention
      approaches.

PMID- 24884952
TI  - Kaliziri extract upregulates tyrosinase, TRP-1, TRP-2 and MITF expression in
      murine B16 melanoma cells.
AB  - BACKGROUND: Kaliziri extract (KZE) is a traditional Uyghur medicine (TUM), used
      by traditional hospitals in China as an injection for treatment of vitiligo for
      more than 30 years. Clinical application has shown that this medicine has obvious
      therapeutic effects. However, its phytochemical analysis and mechanism have not
      been examined. METHODS: KZE was extracted from seeds of Kaliziri [Vernonia
      anthelmintica (L.) Willd.] in ethanol-water (80:20, v/v), its components were
      identified by LC-MS/MS, and the signaling pathway of melanin synthesis in KZE
      treated murine B16 melanoma cells was examined by western blotting. RESULTS:
      Liquid chromatography-mass spectrometry analysis confirmed that the main
      components of KZE are flavonoids. KZE increased the tyrosinase activity and
      melanin content in a dose-dependent manner at concentrations of 5-40 MUg/ml, and
      treatment with 20 MUg/ml of KZE enhanced the expression of tyrosinase in B16
      cells in a time-dependent manner. CONCLUSIONS: KZE induced melanogenesis by
      increasing the expression of TYR, TRP-1, TRP-2 and MITF in B16 cells.

PMID- 24884953
TI  - Casposons: a new superfamily of self-synthesizing DNA transposons at the origin
      of prokaryotic CRISPR-Cas immunity.
AB  - BACKGROUND: Diverse transposable elements are abundant in genomes of cellular
      organisms from all three domains of life. Although transposons are often regarded
      as junk DNA, a growing body of evidence indicates that they are behind some of
      the major evolutionary innovations. With the growth in the number and diversity
      of sequenced genomes, previously unnoticed mobile elements continue to be
      discovered. RESULTS: We describe a new superfamily of archaeal and bacterial
      mobile elements which we denote casposons because they encode Cas1 endonuclease,
      a key enzyme of the CRISPR-Cas adaptive immunity systems of archaea and bacteria.
      The casposons share several features with self-synthesizing eukaryotic DNA
      transposons of the Polinton/Maverick class, including terminal inverted repeats
      and genes for B family DNA polymerases. However, unlike any other known mobile
      elements, the casposons are predicted to rely on Cas1 for integration and
      excision, via a mechanism similar to the integration of new spacers into CRISPR
      loci. We identify three distinct families of casposons that differ in their gene
      repertoires and evolutionary provenance of the DNA polymerases. Deep branching of
      the casposon-encoded endonuclease in the Cas1 phylogeny suggests that casposons
      played a pivotal role in the emergence of CRISPR-Cas immunity. CONCLUSIONS: The
      casposons are a novel superfamily of mobile elements, the first family of
      putative self-synthesizing transposons discovered in prokaryotes. The likely
      contribution of capsosons to the evolution of CRISPR-Cas parallels the
      involvement of the RAG1 transposase in vertebrate immunoglobulin gene
      rearrangement, suggesting that recruitment of endonucleases from mobile elements
      as ready-made tools for genome manipulation is a general route of evolution of
      adaptive immunity.

PMID- 24884954
TI  - A fast and robust iterative algorithm for prediction of RNA pseudoknotted
      secondary structures.
AB  - BACKGROUND: Improving accuracy and efficiency of computational methods that
      predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing
      methods based on free energy minimization tend to be very slow and are limited in
      the types of pseudoknots that they can predict. Incorporating known structural
      information can improve prediction accuracy; however, there are not many methods
      for prediction of pseudoknotted structures that can incorporate structural
      information as input. There is even less understanding of the relative robustness
      of these methods with respect to partial information. RESULTS: We present a new
      method, Iterative HFold, for pseudoknotted RNA secondary structure prediction.
      Iterative HFold takes as input a pseudoknot-free structure, and produces a
      possibly pseudoknotted structure whose energy is at least as low as that of any
      (density-2) pseudoknotted structure containing the input structure. Iterative
      HFold leverages strengths of earlier methods, namely the fast running time of
      HFold, a method that is based on the hierarchical folding hypothesis, and the
      energy parameters of HotKnots V2.0.Our experimental evaluation on a large data
      set shows that Iterative HFold is robust with respect to partial information,
      with average accuracy on pseudoknotted structures steadily increasing from
      roughly 54% to 79% as the user provides up to 40% of the input
      structure.Iterative HFold is much faster than HotKnots V2.0, while having
      comparable accuracy. Iterative HFold also has significantly better accuracy than
      IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a
      robust method for prediction of pseudoknotted RNA secondary structures, whose
      accuracy with more than 5% information about true pseudoknot-free structures is
      better than that of IPknot, and with about 35% information about true pseudoknot
      free structures compares well with that of HotKnots V2.0 while being
      significantly faster. Iterative HFold and all data used in this work are freely
      available at http://www.cs.ubc.ca/~hjabbari/software.php.

PMID- 24884955
TI  - Adherence to statins and LDL-cholesterol goal attainment.
AB  - OBJECTIVES: To examine the relationship between low-density lipoprotein
      cholesterol (LDL-C) goal attainment and adherence to statin medications in
      patients with coronary artery disease (CAD). STUDY DESIGN: Cross-sectional study
      of CAD patients 18 years of age or older in an integrated healthcare system.
      METHODS: Patients dispensed 2 or more statin prescriptions between May 2009 and
      May 2010, were identified. Medication possession ratio (MPR) was calculated to
      estimate adherence. The LDL-C value closest to May 27, 2010, was used to
      determine goal. Adherence and LDL-C goal were defined as 80% or greater MPR and
      less than 100 mg/dL or less than 70 mg/dL, respectively. Electronic medical
      records were used to identify patient demographics and clinical information.
      Logistic regression was used to estimate the effect of these factors on goal
      attainment. RESULTS: A total of 67,100 CAD patients were identified. Overall,
      85.8% had LDL-C less than 100 mg/dL, 32.4% had LDL less than 70 mg/dL, and 79.8%
      were adherent to their statin medication. Over 65% of patients not at LDL-C goal
      less than 100 mg/dL were adherent. Among patients with LDL-C less than 100 mg/dL,
      17.9% were not adherent. Increasing medication adherence was associated with
      improved LDL-C levels. Adherence to statins, male sex, Asian and Hispanic
      race/ethnicity, a higher number of concurrent prescriptions, higher Charlson
      Comorbidity Index, and hypertension were associated with LDL-C goal attainment.
      CONCLUSIONS: Incorporating LDL-C levels and medication adherence at the point of
      care allows providers to focus interventions to address either adherence
      challenges or the need for medication titration in an effort to improve LDL-C
      goal attainment and ultimately reduce morbidity and mortality.

PMID- 24884956
TI  - A team approach to systematic behavioral screening and intervention.
AB  - OBJECTIVES: Unhealthy behaviors are responsible for most chronic disease, ample
      healthcare costs, and around 40% of deaths. This study assessed patient
      satisfaction and behavioral outcomes for a program that enables healthcare
      settings to deliver evidence-based, cost-saving behavioral screening and
      intervention (BSI) services, as recommended by the US Preventive Services Task
      Force and others. STUDY DESIGN: Pre-post program evaluation. METHODS: Thirty-one
      diverse primary care clinics and 2 other sites participated. Over 110,000
      patients completed multibehavioral screening questionnaires. Those with positive
      alcohol or drug screens met with dedicated, on-site health educators for further
      assessment, and then received either reinforcement, brief intervention, or
      referral. Over 300 patients completed satisfaction questionnaires during year 3
      of the program. A pseudo-randomly selected group of 675 patients participated in
      a 6-month follow-up telephone interview. In addition, for a short time in a pilot
      project at 3 clinics, 29 patients received depression screening, collaborative
      care, and behavioral activation, and 22 completed a 3-month follow-up telephone
      interview. RESULTS: Mean patient satisfaction scores for all services exceeded
      4.2 on a 5-point scale. Over 6 months, binge drinking episodes declined by over
      20% for most subgroups. Recent marijuana use decreased by 15%. Depression symptom
      scores decreased by 55%. CONCLUSIONS: With intensive training and ongoing
      support, cost-efficient paraprofessionals can deliver effective alcohol, drug,
      and depression screening and intervention services in busy healthcare settings.
      The approach holds promise for systematically addressing on a population-wide
      basis a variety of important behavioral health determinants and reducing related
      healthcare costs.

PMID- 24884958
TI  - Hepatitis B virus infection testing and prevalence among Asian and Pacific
      Islanders.
AB  - OBJECTIVES: Asian and Pacific Islanders (APIs) constitute less than 6% of the US
      population, but account for more than half of Americans with chronic hepatitis B
      virus (HBV) infection. We sought to examine the effect of country of origin on
      HBV testing and chronic HBV infection prevalence among APIs. METHODS: We analyzed
      demographic and clinical data collected for adults from Kaiser Permanente Hawaii
      with 1 or more healthcare encounters during 2006 to 2008, 12 months or more of
      follow-up before 2009, and no HBV-related diagnosis within 6 months of
      enrollment. Persons who received a test and a positive test result for HBV
      surface antigen or HBV DNA were classified "tested" and with "chronic HBV
      infection," respectively. RESULTS: Of 92,687 eligible APIs, 53,573 (58%) had
      country-of-origin data available. Among those, 41,263 were US born; 28.3% were
      tested; and 1.8% of those tested had chronic HBV infection. Of 12,310 foreign
      born APIs, 30.5% were tested and 7.4% of those tested had chronic HBV infection.
      Foreignborn APIs had higher odds of being tested (odds ratio [OR] = 1.15) and
      testing positive (OR = 4.18) compared with US-born APIs. Persons with 2 or more
      abnormal tests for alanine aminotransferase (ALT) levels had higher odds of
      getting tested (OR = 6.12) and of testing positive (OR = 1.86) compared with
      persons with other ALT levels. CONCLUSIONS: Less than one-third of this managed
      care API population (29% of 53,573) was tested, yet the prevalence of chronic HBV
      infection (3.2%) was 12 times higher than that of the general US population.
      These findings underscore the importance of adherence to HBV testing guidelines
      to identify persons with infection so they may be linked to care.

PMID- 24884957
TI  - Are obese patients assisted in losing weight?
AB  - OBJECTIVES: To quantify obesity inertia (OI) in primary healthcare in the
      Valencian Community (Spain) and determine the related factors. STUDY DESIGN:
      Cross-sectional analysis. METHODS: In 2003, the whole population 40 years and
      older was invited to undergo a check-up. We included all obese persons (body mass
      index [BMI] >= 30 kg/m2) of the first 6 months after the invitation (n = 8687).
      OI was defined as the lack of advice by the healthcare professionals to lose
      weight. Other data recorded: gender, history of cardiovascular risk factors
      (CVRFs) or cardiovascular disease (CVD), groups of BMI (Class I obesity [BMI < 35
      kg/m2] and the rest), age, blood pressure, and lipids. The patients without CVD
      and who were younger than 75 years (n = 7700) were classified according to the
      REGICOR cardiovascular risk as either high or low. The OI was quantified and
      related factors assessed, calculating the adjusted odds ratios (ORs) from
      multivariate models. RESULTS: In the overall sample, OI was 16.6% (95% confidence
      interval [CI], 15.8-17.4). Associated factors: male (OR = 1.19; 95% CI, 1.06
      1.35); no history of hypertension (OR = 0.85; 95% CI, 0.74-0.97), or
      dyslipidaemia (OR = 0.86; 95% CI, 0.73-1.01), or diabetes (OR = 0.80; 95% CI,
      0.64-1.00), or CVD (OR = 0.79; 95% CI, 0.62-1.01); and Class I obesity (OR =
      0.83; 95% CI, 0.72-0.96). In the REGICOR sample, the OI was 16.9% (95% CI, 16.0
      17.7). Associated factors: high REGICOR (OR = 2.27; 95% CI, 1.30-3.98) and Class
      I obesity (OR = 0.82; 95% CI, 0.71-0.95). CONCLUSIONS: OI exists in 1 of every 6
      patients. OI occurs less frequently in patients with a history of CVRF, and more
      frequently in Class I obesity and in those with a high cardiovascular risk.

PMID- 24884959
TI  - Studies of cardiovascular risk factors in polycystic ovary syndrome patients
      combined with subclinical hypothyroidism.
AB  - OBJECTIVE: To investigate cardiovascular risk factors in women with polycystic
      ovary syndrome (PCOS) combined with subclinical hypothyroidism (SCH). PATIENTS: A
      place-controlled study was performed. Group 1: 29 patients with PCOS and SCH;
      Group II: 35 patients with PCOS and normal thyroid function; and Group III: 34
      healthy women with normal thyroid function. MAIN MEASURE INDEXES: Total
      cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high
      density lipoprotein (HDL), Carotid Arterial Intima-Media Thickness (CIMT), free
      triiodothyronine 3 (FT3), free triiodothyronine 4 (FT4), thyroid stimulating
      hormone (TSH), fasting glucose, 1-hour oral glucose tolerance test (OGTT1), 2
      hour oral glucose tolerance test (OGTT2), fasting insulin, insulin after 1 hour
      oral glucose (INS1), insulin after 2 h oral glucose (INS2), HOM-IR = (fasting
      glucose * fasting insulin)/22.5. RESULTS: TG, TC FIN, INS1, and HOM-IR levels
      were significantly higher, but the mean HDL level was significantly lower in
      Group I than in Group II (p < 0.05). LDL cholesterol, FGOGTT1, OGTT2, and insulin
      after 2 h oral glucose were not significantly higher in Group I than in Group II
      (p > 0.05). TG, TC, FIN and INS contents 2 h meal, HOM-IR levels were
      significantly higher, and the mean HDL cholesterol level was significantly lower
      in Group I than in Group III (p < 0.05). Blood glucose levels after 1 and 2 h
      were not significantly higher in Group I than in the Group III (p > 0.05).
      Carotid Arterial Intima-Media Thickness (CIMT) was significantly thicker in Group
      I than other two groups. CONCLUSIONS: The PCOS patients combined with SCH have
      higher risk of cardiovascular risk factors than in controls or in patients with
      PCOS.

PMID- 24884960
TI  - RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell
      malignancy.
AB  - BACKGROUND: The tetraspanin CD63 is a highly N-glycosylated protein that is known
      to regulate cancer malignancy. However, the contribution of glycosylation of CD63
      to cancer malignancy remains unclear. Previously, we reported that ribophorin II
      (RPN2), which is part of an N-oligosaccharyle transferase complex, is responsible
      for drug resistance in breast cancer cells. In this study, we demonstrate that
      cancer malignancy associated with the glycosylation of CD63 is regulated by RPN2.
      RESULTS: Inhibition of RPN2 expression led to a reduction in CD63 glycosylation.
      In addition, the localization of CD63 was deregulated by knockdown of RPN2.
      Interestingly, multidrug resistance protein 1 (MDR1) localization was displaced
      from the cell surface in CD63-silenced cells. CD63 silencing reduced the
      chemoresistance and invasion ability of malignant breast cancer cells.
      Furthermore, the enrichment of CD63/MDR1-double positive cells was associated
      with lymph node metastasis. Taken together, these results indicated that high
      glycosylation of CD63 by RPN2 is implicated in clinical outcomes in breast cancer
      patients. CONCLUSIONS: These findings describe a novel and important function of
      RPN2-mediated CD63 glycosylation, which regulates MDR1 localization and cancer
      malignancy, including drug resistance and invasion.

PMID- 24884962
TI  - Crossed beam reactions of the phenyl (C6H5; X(2)A1) and phenyl-d5 radical (C6D5;
      X(2)A1) with 1,2-butadiene (H2CCCHCH3; X(1)A').
AB  - We explored the reactions on the phenyl (C6H5; X(2)A1) and phenyl-d5 (C6D5;
      X(2)A1) radical with 1,2-butadiene (C4H6; X(1)A') at a collision energy of about
      52 +/- 3 kJ mol(-1) in a crossed molecular beam apparatus. The reaction of phenyl
      with 1,2-butadiene is initiated by adding the phenyl radical with its radical
      center to the pi electron density at the C1/C3 carbon atom of 1,2-butadiene.
      Later, the initial collision complexes isomerize via phenyl group migration from
      the C1/C3 carbon atoms to the C2 carbon atom of the allene moiety of 1,2
      butadiene. The resulting intermediate undergoes unimolecular decomposition
      through hydrogen atom emission from the methyl group of the 1,2-butadiene moiety
      via a rather loose exit transition state leading to 2-phenyl-1,3-butadiene in an
      overall exoergic reaction (DeltaRG = -72 +/- 10 kJ mol(-1)). This finding reveals
      the strong collision-energy dependence of this system when the data are compared
      with those of the phenyl radical with 1,2-butadiene previously recorded at
      collision energies up to 160 kJ mol(-1), with the previous study exhibiting the
      thermodynamically less stable 1-phenyl-3-methylallene (DeltaRG = -33 +/- 10 kJ
      mol(-1)) and 1-phenyl-2-butyne (DeltaRG = -24 +/- 10 kJ mol(-1)) to be the
      dominant products. 

PMID- 24884961
TI  - The neural mobilization technique modulates the expression of endogenous opioids
      in the periaqueductal gray and improves muscle strength and mobility in rats with
      neuropathic pain.
AB  - BACKGROUND: The neural mobilization (NM) technique is a noninvasive method that
      has been proven to be clinically effective in reducing pain; however, the
      molecular mechanisms involved remain poorly understood. The aim of this study was
      to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the
      delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the
      periaqueductal gray (PAG) and improves locomotion and muscle force after chronic
      constriction injury (CCI) in rats. METHODS: The CCI was imposed on adult male
      rats followed by 10 sessions of NM every other day, starting 14 days after the
      CCI injury. At the end of the sessions, the PAG was analyzed using Western blot
      assays for opioid receptors. Locomotion was analyzed by the Sciatic functional
      index (SFI), and muscle force was analyzed by the BIOPAC system. RESULTS: An
      improvement in locomotion was observed in animals treated with NM compared with
      injured animals. Animals treated with NM showed an increase in maximal tetanic
      force of the tibialis anterior muscle of 172% (p < 0.001) compared with the CCI
      group. We also observed a decrease of 53% (p < 0.001) and 23% (p < 0.05) in DOR
      and KOR levels, respectively, after CCI injury compared to those from naive
      animals and an increase of 17% (p < 0.05) in KOR expression only after NM
      treatment compared to naive animals. There were no significant changes in MOR
      expression in the PAG. CONCLUSION: These data provide evidence that a non
      pharmacological NM technique facilitates pain relief by endogenous analgesic
      modulation.

PMID- 24884963
TI  - The effects of chemical interactions and culture history on the colonization of
      structured habitats by competing bacterial populations.
AB  - BACKGROUND: Bacterial habitats, such as soil and the gut, are structured at the
      micrometer scale. Important aspects of microbial life in such spatial ecosystems
      are migration and colonization. Here we explore the colonization of a structured
      ecosystem by two neutrally labeled strains of Escherichia coli. Using time-lapse
      microscopy we studied the colonization of one-dimensional arrays of habitat
      patches linked by connectors, which were invaded by the two E. coli strains from
      opposite sides. RESULTS: The two strains colonize a habitat from opposite sides
      by a series of traveling waves followed by an expansion front. When population
      waves collide, they branch into a continuing traveling wave, a reflected wave and
      a stationary population. When the two strains invade the landscape from opposite
      sides, they remain segregated in space and often one population will displace the
      other from most of the habitat. However, when the strains are co-cultured before
      entering the habitats, they colonize the habitat together and do not separate
      spatially. Using physically separated, but diffusionally coupled, habitats we
      show that colonization waves and expansion fronts interact trough diffusible
      molecules, and not by direct competition for space. Furthermore, we found that
      colonization outcome is influenced by a culture's history, as the culture with
      the longest doubling time in bulk conditions tends to take over the largest
      fraction of the habitat. Finally, we observed that population distributions in
      parallel habitats located on the same device and inoculated with cells from the
      same overnight culture are significantly more similar to each other than to
      patterns in identical habitats located on different devices inoculated with cells
      from different overnight cultures, even tough all cultures were started from the
      same -80 degrees C frozen stock. CONCLUSIONS: We found that the colonization of
      spatially structure habitats by two interacting populations can lead to the
      formation of complex, but reproducible, spatiotemporal patterns. Furthermore, we
      showed that chemical interactions between two populations cause them to remain
      spatially segregated while they compete for habitat space. Finally, we observed
      that growth properties in bulk conditions correlate with the outcome of habitat
      colonization. Together, our data show the crucial roles of chemical interactions
      between populations and a culture's history in determining the outcome of habitat
      colonization.

PMID- 24884964
TI  - A practical approximation algorithm for solving massive instances of
      hybridization number for binary and nonbinary trees.
AB  - BACKGROUND: Reticulate events play an important role in determining evolutionary
      relationships. The problem of computing the minimum number of such events to
      explain discordance between two phylogenetic trees is a hard computational
      problem. Even for binary trees, exact solvers struggle to solve instances with
      reticulation number larger than 40-50. RESULTS: Here we present CycleKiller and
      NonbinaryCycleKiller, the first methods to produce solutions verifiably close to
      optimality for instances with hundreds or even thousands of reticulations.
      CONCLUSIONS: Using simulations, we demonstrate that these algorithms run quickly
      for large and difficult instances, producing solutions that are very close to
      optimality. As a spin-off from our simulations we also present TerminusEst, which
      is the fastest exact method currently available that can handle nonbinary trees:
      this is used to measure the accuracy of the NonbinaryCycleKiller algorithm. All
      three methods are based on extensions of previous theoretical work (SIDMA
      26(4):1635-1656, TCBB 10(1):18-25, SIDMA 28(1):49-66) and are publicly available.
      We also apply our methods to real data.

PMID- 24884965
TI  - Lactobacillus crispatus L1: high cell density cultivation and exopolysaccharide
      structure characterization to highlight potentially beneficial effects against
      vaginal pathogens.
AB  - BACKGROUND: Vaginal lactic acid bacteria defend the host against pathogens
      through a combination of competitive exclusion, competition for nutrients,
      production of antimicrobial substances and through the activation of the immune
      system. A new human isolate named Lactobacillus crispatus L1 was characterized in
      this work, and a preliminary evaluation of its probiotic potential is described
      together with a process to obtain a high productivity of viable biomass. RESULTS:
      In a simulated digestion process 1.8?10(10) cells?ml(-1) survived the gastric
      environment with 80% viability, without being affected by small intestine juices.
      Experiments on six different C sources were performed to analyze growth and
      organic acids production and, glucose, provided the best performances. A
      microfiltration strategy was exploited to improve the cellular yield in 2 L
      fermentation processes, reaching 27 g . l(-1) of dry biomass. Moreover, L.
      crispatus L1 demonstrated a greater stability to high concentrations of lactic
      acid, compared to other lactobacilli. The specific L. crispatus L1
      exopolysaccharide was purified from the fermentation broth and characterized by
      NMR showing structural features and similarity to exopolysaccharides produced by
      pathogenic strains. Live L. crispatus L1 cells strongly reduced adhesion of a
      yeast pathogenic strain, Candida albicans in particular, in adherence assays.
      Interestingly a higher expression of the human defensin HBD-2 was also observed
      in vaginal cells treated with the purified exopolysaccharide, indicating a
      possible correlation with C. albicans growth inhibition. CONCLUSIONS: The paper
      describes the evaluation of L. crispatus L1 as potential vaginal probiotic and
      the fermentation processes to obtain high concentrations of viable cells.

PMID- 24884966
TI  - Is there a role for anterior zone sampling as part of saturation trans-rectal
      ultrasound guided prostate biopsy?
AB  - BACKGROUND: The prostatic anterior zone (AZ) is not targeted routinely by TRUS
      guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ
      tumors, but is often unavailable due to cost or system restrictions. We examined
      the diagnostic yield of office based AZ TRUS-Pbx. METHODS: 127 men at risk for AZ
      tumors were studied: Patients with elevated PSA and previous extended negative
      TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer
      patients (group 2, n = 49). None of the participants had a previous AZ biopsy.
      Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4
      transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single
      urologist under local peri-prostatic anaesthetic, using the B-K Medical US
      System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were
      reviewed by a single specialized uro-pathologist. Multivariate analysis was used
      to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate
      volume, BMI, and number of previous biopsies. RESULTS: Median PSA was 10.4 (group
      1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and
      cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both
      groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ
      cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the
      only zone involved (1.3% and 4.1% respectively). Gleason >= 7 AZ cancers were
      often accompanied by equal grade PZ tumors. In multivariate analysis only
      prostate volume predicted for AZ tumors. Patients detected with AZ tumors had
      significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ
      ultrasonic findings were uncommon (6.3%). CONCLUSIONS: TRUS-Pbx AZ sampling
      rarely improves the diagnostic yield of extended PZ sampling in patients with
      elevated PSA and previous negative biopsies. In low risk prostate cancer patients
      who are followed by active surveillance, AZ sampling changes risk stratification
      in 6% but larger studies are needed to define the role of AZ sampling in this
      population and its correlation with prostatectomy final pathological specimens.

PMID- 24884967
TI  - Critical appraisal of RapidArc radiosurgery with flattening filter free photon
      beams for benign brain lesions in comparison to GammaKnife: a treatment planning
      study.
AB  - BACKGROUND: To evaluate the role of RapidArc (RA) for stereotactic radiosurgery
      (SRS) of benign brain lesions in comparison to GammaKnife (GK) based technique.
      METHODS: Twelve patients with vestibular schwannoma (VS, n = 6) or cavernous
      sinus meningioma (CSM, n = 6) were planned for both SRS using volumetric
      modulated arc therapy (VMAT) by RA. 104 MV flattening filter free photon beams
      with a maximum dose rate of 2400 MU/min were selected. Data were compared against
      plans optimised for GK. A single dose of 12.5 Gy was prescribed. The primary
      objective was to assess treatment plan quality. Secondary aim was to appraise
      treatment efficiency. RESULTS: For VS, comparing best GK vs. RA plans,
      homogeneity was 51.7 +/- 3.5 vs. 6.4 +/- 1.5%; Paddick conformity Index (PCI)
      resulted 0.81 +/- 0.03 vs. 0.84 +/- 0.04. Gradient index (PGI) was 2.7 +/- 0.2
      vs. 3.8 +/- 0.6. Mean target dose was 17.1 +/- 0.9 vs. 12.9 +/- 0.1 Gy. For the
      brain stem, D(1cm3) was 5.1 +/- 2.0 Gy vs 4.8 +/- 1.6 Gy. For the ipsilateral
      cochlea, D(0.1cm3) was 1.7 +/- 1.0 Gy vs. 1.8 +/- 0.5 Gy. For CSM, homogeneity
      was 52.3 +/- 2.4 vs. 12.4 +/- 0.6; PCI: 0.86 +/- 0.05 vs. 0.88 +/- 0.05; PGI: 2.6
      +/- 0.1 vs. 3.8 +/- 0.5; D(1cm3) to brain stem was 5.4 +/- 2.8 Gy vs. 5.2 +/- 2.8
      Gy; D(0.1cm3) to ipsi-lateral optic nerve was 4.2 +/- 2.1 vs. 2.1 +/- 1.5 Gy;
      D(0.1cm3) to optic chiasm was 5.9 +/- 3.1 vs. 4.5 +/- 2.1 Gy. Treatment time was
      53.7 +/- 5.8 (64.9 +/- 24.3) minutes for GK and 4.8 +/- 1.3 (5.0 +/- 0.7) minutes
      for RA for schwannomas (meningiomas). CONCLUSIONS: SRS with RA and FFF beams
      revealed to be adequate and comparable to GK in terms of target coverage,
      homogeneity, organs at risk sparing with some gain in terms of treatment
      efficiency.

PMID- 24884968
TI  - Ensemble-based classification approach for micro-RNA mining applied on diverse
      metagenomic sequences.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenous ~22 nt RNAs that are identified in
      many species as powerful regulators of gene expressions. Experimental
      identification of miRNAs is still slow since miRNAs are difficult to isolate by
      cloning due to their low expression, low stability, tissue specificity and the
      high cost of the cloning procedure. Thus, computational identification of miRNAs
      from genomic sequences provide a valuable complement to cloning. Different
      approaches for identification of miRNAs have been proposed based on homology,
      thermodynamic parameters, and cross-species comparisons. RESULTS: The present
      paper focuses on the integration of miRNA classifiers in a meta-classifier and
      the identification of miRNAs from metagenomic sequences collected from different
      environments. An ensemble of classifiers is proposed for miRNA hairpin prediction
      based on four well-known classifiers (Triplet SVM, Mipred, Virgo and EumiR), with
      non-identical features, and which have been trained on different data. Their
      decisions are combined using a single hidden layer neural network to increase the
      accuracy of the predictions. Our ensemble classifier achieved 89.3% accuracy,
      82.2% f-measure, 74% sensitivity, 97% specificity, 92.5% precision and 88.2%
      negative predictive value when tested on real miRNA and pseudo sequence data. The
      area under the receiver operating characteristic curve of our classifier is 0.9
      which represents a high performance index.The proposed classifier yields a
      significant performance improvement relative to Triplet-SVM, Virgo and EumiR and
      a minor refinement over MiPred.The developed ensemble classifier is used for
      miRNA prediction in mine drainage, groundwater and marine metagenomic sequences
      downloaded from the NCBI sequence reed archive. By consulting the miRBase
      repository, 179 miRNAs have been identified as highly probable miRNAs. Our new
      approach could thus be used for mining metagenomic sequences and finding new and
      homologous miRNAs. CONCLUSIONS: The paper investigates a computational tool for
      miRNA prediction in genomic or metagenomic data. It has been applied on three
      metagenomic samples from different environments (mine drainage, groundwater and
      marine metagenomic sequences). The prediction results provide a set of extremely
      potential miRNA hairpins for cloning prediction methods. Among the ensemble
      prediction obtained results there are pre-miRNA candidates that have been
      validated using miRbase while they have not been recognized by some of the base
      classifiers.

PMID- 24884969
TI  - Sequencing of transcriptomes from two Miscanthus species reveals functional
      specificity in rhizomes, and clarifies evolutionary relationships.
AB  - BACKGROUND: Miscanthus is a promising biomass crop for temperate regions. Despite
      the increasing interest in this plant, limited sequence information has
      constrained research into its biology, physiology, and breeding. The whole genome
      transcriptomes of M. sinensis and M. sacchariflorus presented in this study may
      provide good resources to understand functional compositions of two important
      Miscanthus genomes and their evolutionary relationships. RESULTS: For M.
      sinensis, a total of 457,891 and 512,950 expressed sequence tags (ESTs) were
      produced from leaf and rhizome tissues, respectively, which were assembled into
      12,166 contigs and 89,648 singletons for leaf, and 13,170 contigs and 112,138
      singletons for rhizome. For M. sacchariflorus, a total of 288,806 and 267,952
      ESTs from leaf and rhizome tissues, respectively, were assembled into 8,732
      contigs and 66,881 singletons for leaf, and 8,104 contigs and 63,212 singletons
      for rhizome. Based on the distributions of synonymous nucleotide substitution
      (Ks), sorghum and Miscanthus diverged about 6.2 million years ago (MYA),
      Saccharum and Miscanthus diverged 4.6 MYA, and M. sinensis and M. sacchariflorus
      diverged 1.5 MYA. The pairwise alignment of predicted protein sequences from
      sorghum-Miscanthus and two Miscanthus species found a total of 43,770 and 35,818
      nsSNPs, respectively. The impacts of striking mutations found by nsSNPs were much
      lower between sorghum and Miscanthus than those between the two Miscanthus
      species, perhaps as a consequence of the much higher level of gene duplication in
      Miscanthus and resulting ability to buffer essential functions against
      disturbance. CONCLUSIONS: The ESTs generated in the present study represent a
      significant addition to Miscanthus functional genomics resources, permitting us
      to discover some candidate genes associated with enhanced biomass production. Ks
      distributions based on orthologous ESTs may serve as a guideline for future
      research into the evolution of Miscanthus species as well as its close relatives
      sorghum and Saccharum.

PMID- 24884970
TI  - Comparison of 1-year therapeutic effect of ranibizumab and bevacizumab for myopic
      choroidal neovascularization: a retrospective, multicenter, comparative study.
AB  - BACKGROUND: To compare the long-term efficacy of ranibizumab versus bevacizumab
      for myopic choroidal neovascularization (CNV). METHODS: This was a retrospective,
      multicenter, comparative, non-randomized study of 64 consecutive patients with
      myopic CNV treated with ranibizumab (22 patients) or bevacizumab (42 patients).
      Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical
      coherence tomography were evaluated before and after treatment. All the patients
      were followed for at least 12 months. RESULTS: BCVA (logarithm of the minimal
      angle of resolution) improved from 0.63 +/- 0.30 to 0.43 +/- 0.27, 0.41 +/- 0.37,
      0.40 +/- 0.39, 0.39 +/- 0.43, and 0.39 +/- 0.42 at 1, 2, 3, 6, and 12 months
      after treatment in the ranibizumab group, and from 0.67 +/- 0.28 to 0.52 +/-
      0.31, 0.49 +/- 0.31, 0.47 +/- 0.31, 0.42 +/- 0.32, and 0.46 +/- 0.43 in the
      bevacizumab group (all P < 0.05 compared with baseline BCVA in each group). CFT
      decreased by 20.21%, 19.58%, and 22.43% from the baseline 304 +/- 76 MUm at 3, 6,
      and 12 months after treatment in the former group, and by 15.20%, 15.67%, and
      15.56% from the baseline 297 +/- 62 MUm in the latter group (all P < 0.05
      compared with baseline CFT in each group). BCVA improvement and CFT reduction did
      not statistically differ when compared at the same periods from treatment between
      2 groups. Neither ocular nor systemic safety problems appeared during follow up.
      CONCLUSIONS: This study showed a similar functional and anatomical improvement
      after treatment of ranibizumab and bevacizumab for myopic CNV over a 12-month
      follow-up period.

PMID- 24884971
TI  - Concordance analysis for QTL detection in dairy cattle: a case study of leg
      morphology.
AB  - BACKGROUND: The present availability of sequence data gives new opportunities to
      narrow down from QTL (quantitative trait locus) regions to causative mutations.
      Our objective was to decrease the number of candidate causative mutations in a
      QTL region. For this, a concordance analysis was applied for a leg conformation
      trait in dairy cattle. Several QTL were detected for which the QTL status
      (homozygous or heterozygous for the QTL) was inferred for each individual.
      Subsequently, the inferred QTL status was used in a concordance analysis to
      reduce the number of candidate mutations. METHODS: Twenty QTL for rear leg set
      side view were mapped using Bayes C. Marker effects estimated during QTL mapping
      were used to infer the QTL status for each individual. Subsequently,
      polymorphisms present in the QTL regions were extracted from the whole-genome
      sequences of 71 Holstein bulls. Only polymorphisms for which the status was
      concordant with the QTL status were kept as candidate causative mutations.
      RESULTS: QTL status could be inferred for 15 of the 20 QTL. The number of
      concordant polymorphisms differed between QTL and depended on the number of QTL
      statuses that could be inferred and the linkage disequilibrium in the QTL region.
      For some QTL, the concordance analysis was efficient and narrowed down to a
      limited number of candidate mutations located in one or two genes, while for
      other QTL a large number of genes contained concordant polymorphisms.
      CONCLUSIONS: For regions for which the concordance analysis could be performed,
      we were able to reduce the number of candidate mutations. For part of the QTL,
      the concordant analyses narrowed QTL regions down to a limited number of genes,
      of which some are known for their role in limb or skeletal development in humans
      and mice. Mutations in these genes are good candidates for QTN (quantitative
      trait nucleotides) influencing rear leg set side view.

PMID- 24884972
TI  - Distinguishing the roles of trait and state anxiety on the nature of anxiety
      related attentional biases to threat using a free viewing eye movement paradigm.
AB  - Although attentional biases to threatening information are thought to contribute
      to the development and persistence of anxiety disorders, it is not clear whether
      an attentional bias to threat (ABT) is driven by trait anxiety, state anxiety or
      an interaction between the two. ABT may also be influenced by "top down"
      processes of motivation to attend or avoid threat. In the current study,
      participants high, mid and low in trait anxiety viewed high threat-neutral, mild
      threat-neutral and positive-neutral image pairs for 5 seconds in both calm and
      anxious mood states while their eye movements were recorded. State anxiety alone,
      but not trait anxiety, predicted greater maintenance of attention to high threat
      images (relative to neutral) following the first fixation (i.e., delayed
      disengagement) and over the time course. Motivation was associated with the time
      course of attention as would be expected, such that those motivated to look
      towards negative images showed the greatest ABT over time, and those highly
      motivated to look away from negative images showed the greatest avoidance.
      Interestingly, those ambivalent about where to direct their attention when
      viewing negative images showed the greatest ABT in the first 500 ms of viewing.
      Implications for theory and treatment of anxiety disorders, as well as areas for
      further study, are discussed. 

PMID- 24884973
TI  - Multiple scalp metastases from colonic neuroendocrine carcinoma: case report and
      literature review.
AB  - BACKGROUND: Colonic neuroendocrine neoplasms (NENs) are relatively rare tumors
      with an incidence rate of 0.11-0.21/100,000. NENs account for approximately 0.4%
      of colorectal neoplasms. Cutaneous metastases of colonic neuroendocrine
      carcinomas (NECs) are very infrequent, while cases of scalp metastasis are even
      fewer. Cutaneous metastases are more rare than visceral metastases and usually
      develop later; therefore, cutaneous metastases as initial distant metastases can
      be easily overlooked. This is the second case report of a colonic NEC with scalp
      metastasis. Compared with the previous case, in this instance scalp metastasis
      developed before visceral metastasis, and the cutaneous lesions were confined to
      the scalp alone. CASE PRESENTATION: A 62-year-old Chinese man, who had undergone
      radical surgery for a "locoregional" colonic NEC one and half months before, came
      to our hospital for adjuvant chemotherapy. We found multiple scalp nodules during
      physical examination. Moreover, these nodules had occurred and had not been
      detected prior to the patient undergoing radical surgery. The scalp nodules
      proved to be metastases from colonic NEC as determined using pathological and
      immunohistochemical examinations following lumpectomy. After one and half months,
      visceral metastases were detected in this patient. Ultimately, the patient died
      two months later. CONCLUSIONS: In this report an unusual case of a colonic NEC
      with initial distant metastasis confined to the scalp is presented. This case is
      unusual because of the development of cutaneous metastasis before visceral
      metastasis. The scalp metastasis were initially overlooked, leading to inaccurate
      staging and radical surgery that was not curative. This demonstrates that distant
      metastasis can occur during the early phase of tumor growth in these aggressive
      lesions. Thus, the possibility of distant metastases should be assessed in the
      initial work up to avoid mistaken clinical staging especially when distant
      metastases occur only in skin.

PMID- 24884975
TI  - Electrically and optically tunable plasmonic guest-host liquid crystals with long
      range ordered nanoparticles.
AB  - Practical guest-host devices in which dichroic dye molecules follow electrical
      switching of a liquid crystal host remain elusive for decades despite promising
      efficient displays and emergent applications such as smart windows. This is
      mainly because of poor stability, surface precipitation, and limited means for
      property engineering of the dyes. To overcome these challenges, we develop
      plasmonic metal nanoparticle analogues of dichroic guest-host liquid crystals.
      Nematic dispersions of aligned anisotropic gold nanoparticles are obtained by
      polymer passivation of their surfaces to impose weak tangential boundary
      conditions for orientation of anisotropic host molecules. Control of the ensuing
      surface interactions leads to long-range ordered colloidal dispersions, allowing
      for collective optical and electrical switching of rod- and platelet-like
      nanoparticles. This facile control of mesostructured plasmonic medium's optical
      properties in visible and infrared spectral ranges is of interest for many
      applications. 

PMID- 24884974
TI  - P53/microRNA-34-induced metabolic regulation: new opportunities in anticancer
      therapy.
AB  - MicroRNA-34 (miR-34) is directly regulated by p53, and its potential tumor
      suppressive roles have been studied extensively. As a p53-induced microRNA, miR
      34 functions as a tumor suppressor by playing a role in cell cycle arrest,
      apoptosis and metabolic regulation. Among these p53/miR-34 associated processes,
      apoptosis and cell cycle arrest are known as essential for p53/miR-34-mediated
      tumor suppression. P53-mediated metabolic processes have been shown to play
      pivotal roles in cancer cell biology. Recent studies have also identified several
      miR-34 targets involved in p53/miR-34-induced metabolic regulation. However,
      correlations among these metabolic targets remain to be fully elucidated. In this
      review, we summarize the current progress in the field of metabolic regulation by
      the p53/miR-34 axis and propose future directions for the development of
      metabolic approaches in anticancer therapy. 

PMID- 24884976
TI  - Integrating addiction treatment into primary care using mobile health technology:
      protocol for an implementation research study.
AB  - BACKGROUND: Healthcare reform in the United States is encouraging Federally
      Qualified Health Centers and other primary-care practices to integrate treatment
      for addiction and other behavioral health conditions into their practices. The
      potential of mobile health technologies to manage addiction and comorbidities
      such as HIV in these settings is substantial but largely untested. This paper
      describes a protocol to evaluate the implementation of an E-Health integrated
      communication technology delivered via mobile phones, called Seva, into primary
      care settings. Seva is an evidence-based system of addiction treatment and
      recovery support for patients and real-time caseload monitoring for clinicians.
      METHODS/DESIGN: Our implementation strategy uses three models of organizational
      change: the Program Planning Model to promote acceptance and sustainability, the
      NIATx quality improvement model to create a welcoming environment for change, and
      Rogers's diffusion of innovations research, which facilitates adaptations of
      innovations to maximize their adoption potential. We will implement Seva and
      conduct an intensive, mixed-methods assessment at three diverse Federally
      Qualified Healthcare Centers in the United States. Our non-concurrent multiple
      baseline design includes three periods - pretest (ending in four months of
      implementation preparation), active Seva implementation, and maintenance - with
      implementation staggered at six-month intervals across sites. The first site will
      serve as a pilot clinic. We will track the timing of intervention elements and
      assess study outcomes within each dimension of the Reach, Effectiveness,
      Adoption, Implementation, and Maintenance framework, including effects on
      clinicians, patients, and practices. Our mixed-methods approach will include
      quantitative (e.g., interrupted time-series analysis of treatment attendance,
      with clinics as the unit of analysis) and qualitative (e.g., staff interviews
      regarding adaptations to implementation protocol) methods, and assessment of
      implementation costs. DISCUSSION: If implementation is successful, the field will
      have a proven technology that helps Federally Qualified Health Centers and
      affiliated organizations provide addiction treatment and recovery support, as
      well as a proven strategy for implementing the technology. Seva also has the
      potential to improve core elements of addiction treatment, such as referral and
      treatment processes. A mobile technology for addiction treatment and accompanying
      implementation model could provide a cost-effective means to improve the lives of
      patients with drug and alcohol problems. TRIAL REGISTRATION: ClinicalTrials.gov
      (NCT01963234).

PMID- 24884977
TI  - Population prevalence of ultrasound features of osteoarthritis in the hand, knee
      and hip at age 63 years: the Newcastle thousand families birth cohort.
AB  - BACKGROUND: Musculoskeletal ultrasound has been found to be more sensitive than
      radiographs in detecting osteophytes. Our objective was to measure the prevalence
      of features of osteoarthritis (OA), in the dominant hand, knees and hips using
      ultrasound, within the Newcastle Thousand Families birth cohort. METHODS:
      Participants were aged 61-63 (mean 63) years. Knee images were scored for
      presence of osteophytes and effusion. Hip images were scored for the presence of
      osteophytes and femoral head abnormality. The first carpometacarpal joint,
      metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints
      of the index finger (dominant hand) were imaged for osteophytes. RESULTS: Among
      311 participants, prevalence of osteophytes at the distal interphalangeal joint
      was 70% while it was 23%, 10% and 41% for index proximal interphalangeal and
      metacarpophalangeal and thumb base carpometacarpal joints respectively.
      Prevalence of knee osteophytes was 30%, hip OA was 41%. Prevalence of knee
      effusions was 24% (right) and 20% (left). Ultrasound evidence of generalised OA
      (48%) and isolated hand OA (31%) was common, compared to isolated hip or knee OA
      (5%) and both hip and knee OA (3%). CONCLUSION: This is the first study to assess
      prevalence of ultrasound features of OA in a population-based sample. The higher
      prevalence of hand/hip OA, when compared to previous radiographic studies,
      supports the hypothesis that ultrasound is more sensitive than radiography in
      detecting OA, particularly for osteophytes.

PMID- 24884978
TI  - Estimating trematode prevalence in snail hosts using a single-step duplex PCR:
      how badly does cercarial shedding underestimate infection rates?
AB  - BACKGROUND: Trematode communities often consist of different species exploiting
      the same host population, with two or more trematodes sometimes co-occuring in
      the same host. A commonly used diagnostic method to detect larval trematode
      infections in snails has been based on cercarial shedding, though it is often
      criticized as inaccurate. In the present study we compare infection prevalences
      determined by cercarial emission with those determined, for the first time, by
      molecular methods, allowing us to quantify the underestimation of single and
      double infections based on cercarial emission. We thus developed a duplex PCR for
      two host-parasite systems, to specifically differentiate between single and
      double infections. The Ebro samples include two morphologically similar
      opecoelids, whereas the Otago samples include two morphologically different
      larval trematodes. METHODS: Snails were screened for infections by incubating
      them individually to induce cercarial emission, thus determining infection
      following the "classical" detection method. Snail tissue was then removed and
      fixed for the duplex PCR. After obtaining ITS rDNA sequences, four species
      specific primers were designed for each snail-trematode system, and duplex PCR
      prevalence was determined for each sample. Results from both methods were
      statistically compared using the McNemar's Chi-squared test and Cohen's Kappa
      Statistic for agreement between outcomes. RESULTS: Overall infection prevalences
      determined by duplex PCR were consistently and substantially higher than those
      based on cercarial shedding: among Ebro samples, between 17.9% and 60.1% more
      snails were found infected using the molecular method, whereas in the Otago
      samples, the difference was between 9.9% and 20.6%. Kappa values generally
      indicated a fair to substantial agreement between both detection methods, showing
      a lower agreement for the Ebro samples. CONCLUSIONS: We demonstrate that
      molecular detection of single and double infections by duplex PCR strongly
      outcompetes the classical method. Detection failure is most likely due to
      immature and covert infections, however, the higher incidence of misidentified
      double infections in the Ebro samples arises from morphological similarity of
      closely-related species. The higher accuracy of the duplex PCR method also adds
      to our understanding of community structure of larval trematodes in snail hosts,
      by providing a clearer assessment of the importance of interspecific interactions
      within the host.

PMID- 24884979
TI  - A comparison between reported therapy staffing levels and the department of
      health therapy staffing guidelines for stroke rehabilitation: a national survey.
AB  - BACKGROUND: This study compared reported staffing levels for stroke care within
      UK in-patient stroke units to stroke strategy staffing guidelines published by
      the UK Department of Health and the Royal College of Physicians. The purpose was
      to explore the extent to which stroke teams are meeting recommended staffing
      levels. METHOD: The data analyzed in this report consisted of the detailed
      therapist staffing levels reported in the demographic section of our national
      survey to determine upper limb treatment in stroke units (the ATRAS survey). A
      contact list of stroke practitioners was therefore compiled primarily in
      collaboration with the 28 National Stroke Improvement Networks. Geographic
      representation of the network areas was obtained by applying the straight-forward
      systematic sampling method and the N(th) name selection technique to each Network
      list. In total 192 surveys were emailed to stroke care providers around England.
      This included multiple contacts within stroke teams (e.g. a stroke consultant and
      a stroke co-coordinator) to increase awareness of the survey. RESULTS: A total of
      53 surveys were returned from stroke teams and represented 20 of the 28 network
      areas providing 71% national coverage. To compare reported staffing levels to
      suggested DoH guidelines, analysis was conducted on 19 of the 37 inpatient
      hospital care units that had no missing data for staff numbers, unit bed numbers,
      number of stroke patients treated per annum, average unit length-of-stay, and
      average unit occupancy rates. Only 42% of units analyzed reached the DoH
      guideline for physiotherapy and fewer than 16% of the units reached the guideline
      for speech & language therapy. By contrast, 84% of units surveyed reached the
      staffing guideline for occupational therapy. However, a post-hoc analysis
      highlights this as an irregularity in the DoH guidelines, revealing that all
      therapies are challenged to provide the recommended therapy time. CONCLUSIONS:
      Most in-patient stroke units are operating below the DoH guidelines and are
      therefore challenged in providing the recommended amount of therapy and patient
      time to facilitate optimal functional recovery for stroke patients.

PMID- 24884980
TI  - Intra-abdominal desmoid tumor mimicking gastric cancer recurrence: a case report.
AB  - Intra-abdominal desmoid tumors are rare and most often occur in patients with a
      history of familial adenomatous polyposis, surgery, or pregnancy. We report a
      case of an intra-abdominal desmoid tumor mimicking the recurrence of gastric
      cancer. A 57-year-old male had undergone distal gastrectomy for advanced gastric
      cancer. Serum levels of carcinoembryonic antigen were found to be elevated 27
      months after surgery. Computed tomography revealed a 15-mm mass in the mesentery
      of the transverse colon. In addition, radiotracer fluorodeoxyglucose uptake of
      the tumor was detected by positron emission tomography. The patient was diagnosed
      with gastric cancer recurrence, and chemotherapy consisting of cisplatin and S-1
      was commenced. After five courses of chemotherapy, although no significant
      clinical response was seen, no new lesions were seen either. Thus, a curative
      resection of the recurrent tumor seemed possible, which was successfully
      performed. Histological examination of the resected specimen revealed spindle
      shaped tumor cells with collagen fiber progression; no cancer cells were
      detected. The tumor was diagnosed as an intra-abdominal desmoid tumor. We report
      a rare case of an intra-abdominal desmoid tumor that mimicked a recurrent tumor
      arising from gastric cancer. In patients with history of surgery for intra
      abdominal malignancies, it may be difficult to distinguish the recurrence of
      malignancy from desmoid tumors but the possibility of desmoid tumors must be
      considered in the differential diagnosis. 

PMID- 24884981
TI  - Transcranial Doppler ultrasonography should it be the first choice for persistent
      foramen ovale screening?
AB  - BACKGROUND: Persistent foramen ovale (PFO) is considered a cause of cryptogenic
      stroke and a risk factor for neurological events in young patients. The reference
      standard for identifying a PFO is contrast-enhanced transesophageal
      echocardiography (TEE).The goal of this study was to evaluate the feasibility of
      transcranial color Doppler (TCD) and its diagnostic sensitivity compared with
      TEE. METHODS: We investigated 420 patients admitted to our department with
      cryptogenic stroke, transient ischemic attacks or other neurological symptoms.
      All patients underwent TCD and TEE evaluation. TCD and TEE examinations were
      performed according to a standardized procedure: air-mixed saline was injected
      into the right antecubital vein three times, while the Doppler signal was
      recorded during the Valsalva maneuver. During TCD the passage of contrast into
      the right-middle cerebral artery was recorded 25 seconds following the Valsalva
      maneuver. RESULTS: We detected a right-to-left shunt in 220 patients (52.3%) and
      no-shunts in 159 patients (37.9%) with both TCD and TEE. In 20 (4.8%) patients
      TEE did not reveal contrast passage which was then detected by TCD. In 21 (5.0%)
      patients only TEE revealed a PFO. The feasibility of both methods was 100%. TCD
      had a sensitivity of 95% and a specificity of 92% in the diagnosis of PFO.
      CONCLUSIONS: TCD has a relatively good sensitivity and specificity. TCD and TEE
      are complementary diagnostic tests for PFO, but TCD should be recommended as the
      first choice for screening because of its simplicity, non-invasive character, low
      cost and high feasibility.

PMID- 24884982
TI  - Magnetic resonance imaging of the brain in adults with severe falciparum malaria.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) allows detailed study of structural
      and functional changes in the brain in patients with cerebral malaria. METHODS:
      In a prospective observational study in adult Bangladeshi patients with severe
      falciparum malaria, MRI findings in the brain were correlated with clinical and
      laboratory parameters, retinal photography and optic nerve sheath diameter (ONSD)
      ultrasound (a marker of intracranial pressure). RESULTS: Of 43 enrolled patients,
      31 (72%) had coma and 12 (28%) died. MRI abnormalities were present in 79%
      overall with mostly mild changes in a wide range of anatomical sites. There were
      no differences in MRI findings between patients with cerebral and non-cerebral or
      fatal and non-fatal disease. Subtle diffuse cerebral swelling was common (n =
      22/43), but mostly without vasogenic oedema or raised intracranial pressure
      (ONSD). Also seen were focal extracellular oedema (n = 11/43), cytotoxic oedema
      (n = 8/23) and mildly raised brain lactate on magnetic resonance spectroscopy (n
      = 5/14). Abnormalities were much less prominent than previously described in
      Malawian children. Retinal whitening was present in 36/43 (84%) patients and was
      more common and severe in patients with coma. CONCLUSION: Cerebral swelling is
      mild and not specific to coma or death in adult severe falciparum malaria. This
      differs markedly from African children. Retinal whitening, reflecting
      heterogeneous obstruction of the central nervous system microcirculation by
      sequestered parasites resulting in small patches of ischemia, is associated with
      coma and this process is likely important in the pathogenesis.

PMID- 24884983
TI  - The significance of cone beam computed tomography for the visualization of
      anatomical variations and lesions in the maxillary sinus for patients hoping to
      have dental implant-supported maxillary restorations in a private dental office
      in Japan.
AB  - OBJECTIVES: The purpose of the present study was to elucidate the significance of
      cone bean computed tomography (CBCT) for patients hoping to undergo implant
      supported restorations of the maxilla. Therefore, two studies were planned. One
      was to compare the prevalence of anatomic variations and lesions in the maxillary
      sinus on CBCT of patients hoping to undergo implant-supported restorations of the
      maxilla with that in patients with other chief complaints in a private dental
      office in Japan. The other study was to elucidate the limitations of panoramic
      radiographs in the detection of anatomic variations and lesions in the maxillary
      sinus. STUDY DESIGN: Sixty-one pairs of panoramic radiographs and CBCT were
      retrospectively analyzed in two groups of patients, those who hoped to undergo
      implant-supported restorations in the maxilla (Implant group) and those who did
      not (Non-implant group). The presence of anatomic variations and lesions in the
      maxillary sinus were analyzed. RESULTS: The detection rate of mucosal thickening
      was significantly higher in the Implant group than in the Non-implant group. The
      detection rates for the features analyzed were significantly lower on panoramic
      radiographs. In particular, the detection rates of internal and anterior
      locations of some features were noticeably lower on panoramic radiographs. A
      significant relationship was found between the change in the detection rate on
      panoramic radiographs and the widths of mucosal thickening or the lengths of the
      major axis of SOLs in the maxillary sinus. If the width of mucosal thickening or
      the length of the major axis of SOLs was <3 mm or <4 mm, respectively, the
      detection rate on panoramic radiographs was significantly decreased. CONCLUSION:
      CBCT is important for patients hoping to undergo implant-supported restorations
      of the maxilla because of the mucosal thickening in the maxillary sinus in such
      patients and their lower detection rates on panoramic radiographs.

PMID- 24884984
TI  - Identification of factors associated with diagnostic error in primary care.
AB  - BACKGROUND: Missed, delayed or incorrect diagnoses are considered to be
      diagnostic errors. The aim of this paper is to describe the methodology of a
      study to analyse cognitive aspects of the process by which primary care (PC)
      physicians diagnose dyspnoea. It examines the possible links between the use of
      heuristics, suboptimal cognitive acts and diagnostic errors, using Reason's
      taxonomy of human error (slips, lapses, mistakes and violations). The influence
      of situational factors (professional experience, perceived overwork and fatigue)
      is also analysed. METHODS: Cohort study of new episodes of dyspnoea in patients
      receiving care from family physicians and residents at PC centres in Granada
      (Spain). With an initial expected diagnostic error rate of 20%, and a sampling
      error of 3%, 384 episodes of dyspnoea are calculated to be required. In addition
      to filling out the electronic medical record of the patients attended, each
      physician fills out 2 specially designed questionnaires about the diagnostic
      process performed in each case of dyspnoea. The first questionnaire includes
      questions on the physician's initial diagnostic impression, the 3 most likely
      diagnoses (in order of likelihood), and the diagnosis reached after the initial
      medical history and physical examination. It also includes items on the
      physicians' perceived overwork and fatigue during patient care. The second
      questionnaire records the confirmed diagnosis once it is reached. The complete
      diagnostic process is peer-reviewed to identify and classify the diagnostic
      errors. The possible use of heuristics of representativeness, availability, and
      anchoring and adjustment in each diagnostic process is also analysed. Each audit
      is reviewed with the physician responsible for the diagnostic process. Finally,
      logistic regression models are used to determine if there are differences in the
      diagnostic error variables based on the heuristics identified. DISCUSSION: This
      work sets out a new approach to studying the diagnostic decision-making process
      in PC, taking advantage of new technologies which allow immediate recording of
      the decision-making process.

PMID- 24884985
TI  - No global consensus: a cross-sectional survey of maternal weight policies.
AB  - BACKGROUND: Growing evidence suggests that maternal prepregnancy weight and
      gestational weight gain are risk factors for perinatal complications and
      subsequent maternal and child health. Postpartum weight retention is also
      associated with adverse birth outcomes and maternal obesity. Clinical guidelines
      addressing healthy weight before, during, and after pregnancy have been
      introduced in some countries, but at present a systematic accounting for these
      policies has not been conducted. The objective of the present study was to
      conduct a cross-national comparison of maternal weight guidelines. METHODS: This
      cross sectional survey administered a questionnaire online to key informants with
      expertise on the subject of maternal weight to assess the presence and content of
      preconceptional, pregnancy and postpartum maternal weight guidelines, their
      rationale and availability. We searched 195 countries, identified potential
      informants in 80 and received surveys representing 66 countries. We estimated the
      proportion of countries with guidelines by region, income, and formal or informal
      policy, and described and compared guideline content, including a rubric to
      assess presence or absence of 4 guidelines: encourage healthy preconceptional
      weight, antenatal weighing, encourage appropriate gestational gain, and encourage
      attainment of healthy postpartum weight. RESULTS: Fifty-three countries reported
      either a formal or informal policy regarding maternal weight. The majority of
      these policies included guidelines to assess maternal weight at the first
      prenatal visit (90%), to monitor gestational weight gain during pregnancy (81%),
      and to provide recommendations to women about healthy gestational weight gain
      (62%). Guidelines related to preconceptional (42%) and postpartum (13%) weight
      were less common. Only 8% of countries reported policies that included all 4
      fundamental guidelines. Guideline content and rationale varied considerably
      between countries, and respondents perceived that within their country, policies
      were not widely known. CONCLUSIONS: These results suggest that maternal weight is
      a concern throughout the world. However, we found a lack of international
      consensus on the content of guidelines. Further research is needed to understand
      which recommendations or interventions work best with respect to maternal weight
      in different country settings, and how pregnancy weight policies impact clinical
      practices and health outcomes for the mother and child.

PMID- 24884987
TI  - Vitamin D and assisted reproduction technologies: current concepts.
AB  - Accumulating evidence from animal and human studies suggests that vitamin D is
      involved in many functions of the human reproductive system in both genders, but
      no comprehensive analysis of the potential relationship between vitamin D status
      and Assisted Reproduction Technologies (ART) outcomes is currently available. On
      this basis, the purpose of this systematic review and meta-analysis was to
      perform an in-depth evaluation of clinical studies assessing whether vitamin D
      status of patients undergoing ART could be related to cycle outcome variables.
      This issue is of interest considering that vitamin D deficiency is easily
      amenable to correction and oral vitamin D supplementation is cheap and without
      significant side effects. Surprisingly, no studies are currently available
      assessing vitamin D status among male partners of couples undergoing ART, while
      seven studies on vitamin D status of women undergoing controlled ovarian
      hyperstimulation (COH) for ART were found and included in the review. Results
      show that vitamin D deficiency is highly prevalent among women undergoing COH,
      ranging from 21% to 31% across studies conducted in Western countries and
      reaching 75-99% in Iranian studies. Data on vitamin D deficiency (25
      hydroxyvitamin D serum levels <20 ng/ml) in relation to ART outcomes could be
      extracted from three studies and included in the meta-analysis, yielding a common
      risk ratio (RR) of 0.89 (95% CI 0.53-1.49) and showing a lower but not
      statistically significant likelihood of clinical pregnancy for vitamin-D
      deficient women compared with vitamin-D-sufficient patients. In conclusion, there
      is insufficient evidence to support the routine assessment of vitamin D status to
      predict the clinical pregnancy rate in couples undergoing ART. The partly
      conflicting results of the available studies, potentially explaining the lack of
      statistical significance for a negative influence of vitamin D deficiency on
      clinical pregnancy rate, are likely secondary to confounders and insufficient
      sample size, and further larger cohort and randomised controlled studies are
      required. 

PMID- 24884986
TI  - Mental health related determinants of parenting stress among urban mothers of
      young children--results from a birth-cohort study in Ghana and Cote d'Ivoire.
AB  - BACKGROUND: There are limited data on the parenting stress (PS) levels in sub
      Saharan African mothers and on the association between ante- and postnatal
      depression and anxiety on PS. METHODS: A longitudinal birth cohort of 577 women
      from Ghana and Cote d'Ivoire was followed from the 3rd trimester in pregnancy to
      2 years postpartum between 2010 and 2013. Depression and anxiety were assessed by
      the Patient Health Questionnaire depression module (PHQ-9) and the Generalized
      Anxiety Disorder (GAD-7) at baseline, 3 month, 12 month and 24 month postpartum.
      PS was measured using the Parenting Stress Index-Short Form (PSI-SF) at 3, 12 and
      24 month. The mean total PS score and the subscale scores were compared among
      depressed vs. non-depressed and among anxious vs. non-anxious mothers at 3, 12
      and 24 month postpartum. The proportions of clinical PS (PSI-SF raw score > 90)
      in depressed vs. non-depressed and anxious vs. non-anxious mothers were also
      compared. A generalized estimating equation (GEE) approach was used to estimate
      population-averaged associations between women's depression/anxiety and PS
      adjusting for age, child sex, women's anemia, education, occupation, spouse's
      education, and number of sick child visits. RESULTS: A total of 577, 531 and 264
      women completed the PS assessment at 3 month, 12 month and 24 month postpartum
      across the two sites and the prevalences of clinical PS at each time point was
      33.1%, 24.4% and 14.9% in Ghana and 30.2%, 33.5% and 22.6% in Cote d'Ivoire,
      respectively. At all three time points, the PS scores were significantly higher
      among depressed mothers vs. non-depressed mothers. In the multivariate regression
      analyses, antepartum and postpartum depression were consistently associated with
      PS after adjusting for other variables. CONCLUSIONS: Parenting stress is frequent
      and levels are high compared with previous studies from high-income countries.
      Antepartum and postpartum depression were both associated with PS, while
      antepartum and postpartum anxiety were not after adjusting for confounders. More
      quantitative and qualitative data are needed in sub-Saharan African populations
      to assess the burden of PS and understand associated mechanisms. Should our
      findings be replicated, it appears prudent to design and subsequently evaluate
      intervention strategies.

PMID- 24884988
TI  - The chemical arsenal of Burkholderia pseudomallei is essential for pathogenicity.
AB  - Increasing evidence has shown that small-molecule chemistry in microbes (i.e.,
      secondary metabolism) can modulate the microbe-host response in infection and
      pathogenicity. The bacterial disease melioidosis is conferred by the highly
      virulent, antibiotic-resistant pathogen Burkholderia pseudomallei (BP). Whereas
      some macromolecular structures have been shown to influence BP virulence (e.g.,
      secretion systems, cellular capsule, pili), the role of the large cryptic
      secondary metabolome encoded within its genome has been largely unexplored for
      its importance to virulence. Herein we demonstrate that BP-encoded small-molecule
      biosynthesis is indispensible for in vivo BP pathogenicity. Promoter exchange
      experiments were used to induce high-level molecule production from two gene
      clusters (MPN and SYR) found to be essential for in vivo virulence. NMR
      structural characterization of these metabolites identified a new class of
      lipopeptide biosurfactants/biofilm modulators (the malleipeptins) and syrbactin
      type proteasome inhibitors, both of which represent overlooked small-molecule
      virulence factors for BP. Disruption of Burkholderia virulence by inhibiting the
      biosynthesis of these small-molecule biosynthetic pathways may prove to be an
      effective strategy for developing novel melioidosis-specific therapeutics. 

PMID- 24884989
TI  - A positive association between anxiety disorders and cannabis use or cannabis use
      disorders in the general population--a meta-analysis of 31 studies.
AB  - BACKGROUND: The aim of the current study was to investigate the association
      between anxiety and cannabis use/cannabis use disorders in the general
      population. METHODS: A total of N = 267 studies were identified from a systematic
      literature search (any time- March 2013) of Medline and PsycInfo databases, and a
      hand search. The results of 31 studies (with prospective cohort or cross
      sectional designs using non-institutionalised cases) were analysed using a random
      effects meta-analysis with the inverse variance weights. Lifetime or past 12
      month cannabis use, anxiety symptoms, and cannabis use disorders (CUD; dependence
      and/or abuse/harmful use) were classified according to DSM/ICD criteria or scores
      on standardised scales. RESULTS: There was a small positive association between
      anxiety and either cannabis use (OR = 1.24, 95% CI: 1.06-1.45, p = .006; N = 15
      studies) or CUD (OR = 1.68, 95% CI: 1.23-2.31, p = .001; N = 13 studies), and
      between comorbid anxiety + depression and cannabis use (OR = 1.68, 95% CI: 1.17
      2.40, p = .004; N = 5 studies). The positive associations between anxiety and
      cannabis use (or CUD) were present in subgroups of studies with ORs adjusted for
      possible confounders (substance use, psychiatric illness, demographics) and in
      studies with clinical diagnoses of anxiety. Cannabis use at baseline was
      significantly associated with anxiety at follow-up in N = 5 studies adjusted for
      confounders (OR = 1.28, 95% CI: 1.06-1.54, p = .01). The opposite relationship
      was investigated in only one study. There was little evidence for publication
      bias. CONCLUSION: Anxiety is positively associated with cannabis use or CUD in
      cohorts drawn from some 112,000 non-institutionalised members of the general
      population of 10 countries.

PMID- 24884991
TI  - A genome scan for Plasmodium falciparum malaria identifies quantitative trait
      loci on chromosomes 5q31, 6p21.3, 17p12, and 19p13.
AB  - BACKGROUND: Genome-wide studies have mapped several loci controlling Plasmodium
      falciparum mild malaria and parasitaemia, only two of them being significant at
      the genome level. The objective of the present study was to identify malaria
      resistance loci in individuals living in Burkina Faso. METHODS: A genome scan
      that involved 314 individuals belonging to 63 families was performed. Markers
      located within chromosomes 6p21.3 and 17p12 were genotyped in 247 additional
      individuals belonging to 55 families. The linkage and the association of markers
      with parasitaemia and mild malaria were assessed by using the maximum-likelihood
      binomial method extended to quantitative trait linkage and the quantitative trait
      disequilibrium test, respectively. RESULTS: Multipoint linkage analysis showed a
      significant linkage of mild malaria to chromosome 6p21.3 (LOD score 3.73, P = 1.7
      10-5), a suggestive linkage of mild malaria to chromosome 19p13.12 (LOD score
      2.50, P = 3.5 10-4), and a suggestive linkage of asymptomatic parasitaemia to
      chromosomes 6p21.3 (LOD score 2.36, P = 4.9 10-4) and 17p12 (LOD score 2.87, P =
      1.4 10-4). Genome-wide family-based association analysis revealed a significant
      association between three chromosome 5q31 markers and asymptomatic parasitaemia,
      whereas there was no association with mild malaria. When taking into account 247
      additional individuals, a significant linkage of asymptomatic parasitaemia to
      chromosome 17p12 (LOD score 3.6, P = 2 10-5) was detected. CONCLUSION: A new
      genome-wide significant malaria locus on chromosome 17p12 and a new suggestive
      locus on chromosome 19p13.12 are reported. Moreover, there was evidence that
      confirmed the influence of chromosomes 5q31 and 6p21.3 as loci controlling mild
      malaria or asymptomatic parasitaemia.

PMID- 24884990
TI  - Transcriptome profiling of liver of non-genetic low birth weight and long term
      health consequences.
AB  - BACKGROUND: It is believed that the main factors of low prenatal growth in
      mammals are genetic and environmental. We used isogenic mice maintained in
      standard conditions to analyze how natural non-genetic microsomia (low birth
      weight) is produced in inbred mice and its long term effect on health. To better
      understand the molecular basis of non-genetic microsomia, we undertook
      transcriptome profiling of both male and female livers from small and normal size
      mice at birth. RESULTS: Naturally occurring neonatal microsomia was defined as a
      gender-specific weanling weight under the 10th percentile of the colony. Birth
      weight variation was similar in inbred and outbred lines. Mice were phenotyped by
      weight, size, blood pressure, organ size, their response to a glucose challenge,
      and survival rates. Regardless of diet, adult mice born with microsomia showed a
      significantly lower body weight and size, and differences in the weight of
      several organs of microsomic adult mice compared to normal birth weight adults
      were found. After a high-fat diet, microsomic mice were less prone to obesity,
      showing a better glucose tolerance and lower blood pressure. Through a
      transcriptome analysis, we detected a different pattern of mRNA transcription in
      the liver at birth comparing male vs female and microsomic vs normal mice, noting
      some modifications in epigenetic regulatory genes in females and modifications in
      some growth factor genes in males. Finally, using embryo transfer of embryos of
      different quality and age, we identified a putative preimplantation origin of
      this non-genetic microsomia. CONCLUSIONS: (1) neonatal microsomia is not always a
      risk factor for adult metabolic syndrome, (2) neonatal non-genetic microsomia
      displays changes in the expression of important epigenetic genes and changes in
      liver mRNA transcription profile at birth, exaggerating sexual dimorphism, and
      (3) random preimplantation phenotypic variability could partially explain body
      birth weight variation in isogenic lines.

PMID- 24884992
TI  - Genetic distance as an alternative to physical distance for definition of gene
      units in association studies.
AB  - BACKGROUND: Some association studies, as the implemented in VEGAS, ALIGATOR, i
      GSEA4GWAS, GSA-SNP and other software tools, use genes as the unit of analysis.
      These genes include the coding sequence plus flanking sequences. Polymorphisms in
      the flanking sequences are of interest because they involve cis-regulatory
      elements or they inform on untyped genetic variants trough linkage
      disequilibrium. Gene extensions have customarily been defined as +/-50 Kb. This
      approach is not fully satisfactory because genetic relationships between
      neighbouring sequences are a function of genetic distances, which are only poorly
      replaced by physical distances. RESULTS: Standardized recombination rates (SRR)
      from the deCODE recombination map were used as units of genetic distances. We
      searched for a SRR producing flanking sequences near the +/-50 Kb offset that has
      been common in previous studies. A SRR>=2 was selected because it led to gene
      extensions with median length=45.3 Kb and the simplicity of an integer value. As
      expected, boundaries of the genes defined with the +/-50 Kb and with the SRR>=2
      rules were rarely concordant. The impact of these differences was illustrated
      with the interpretation of top association signals from two large studies
      including many hits and their detailed analysis based in different criteria. The
      definition based in genetic distance was more concordant with the results of
      these studies than the based in physical distance. In the analysis of 18 top
      disease associated loci form the first study, the SRR>=2 genes led to a fully
      concordant interpretation in 17 loci; the +/-50 Kb genes only in 6.
      Interpretation of the 43 putative functional genes of the second study based in
      the SRR>=2 definition only missed 4 of the genes, whereas the based in the +/-50
      Kb definition missed 10 genes. CONCLUSIONS: A gene definition based on genetic
      distance led to results more concordant with expert detailed analyses than the
      commonly used based in physical distance. The genome coordinates for each gene
      are provided to maintain a simple use of the new definitions.

PMID- 24884993
TI  - Characterization of two new monoclonal antibodies against human papillomavirus
      type 16 L1 protein.
AB  - BACKGROUND: Human papillomavirus type 16 (HPV16) infection is implicated in
      cervical carcinogenesis. This study aimed to characterize two new monoclonal
      antibodies (mAbs) against HPV L1 protein. METHODS: The immunocompetence of AE3
      and AG7 mAbs for HPV L1 protein was evaluated by Western blot analysis,
      immunostaining, hemagglutination inhibition assay, and ELISA. The heavy chain
      variable region (VH) and light chain variable region (VL) of AE3 and AG7 mAbs
      were sequenced and analyzed. RESULTS: Both mAbs specifically recognized HPV16 L1
      and virus-like particles (VLPs). Both the affinity and the titer of AE3 mAb were
      higher than that of AG7. There were differences in sequences in the complementary
      determining regions (CDR) 2 and 3 of VL, as well as in the CDR1 and CDR3 of VH.
      The two mAbs have distinct predicted three-dimensional structures. CONCLUSIONS:
      We characterized two mAbs neutralizing antibodies for HPV L1 protein, which would
      help develop genetic-engineered neutralizing antibodies against HPV16 for
      diagnostic and therapeutic purposes.

PMID- 24884994
TI  - Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant
      bilateral myelolipomas from patients with congenital adrenal hyperplasia.
AB  - BACKGROUND: Although chronic adrenocorticotropic hormone (ACTH) and androgen
      hyperstimulation are assumed to be involved in the pathogenesis of adrenal
      myelolipomas associated with poor-compliance patients with congenital adrenal
      hyperplasia (CAH), the expression of their receptors has not yet been
      demonstrated in these tumors so far. METHODS: We analyzed Melanocortin 2 receptor
      (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1)
      expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas
      from two untreated simple virilizing CAH cases and in two sporadic adrenal
      myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat
      numbers in AR exon 1 gene were evaluated in the 4 cases. RESULTS: The MC2R gene
      was overexpressed in myelolipomas from 3 out of 4 patients. AR overexpression was
      detected in 2 tumors: a giant bilateral myelolipoma in a CAH patient and a
      sporadic case. Simultaneous overexpression of AR and MC2R genes was found in two
      of the cases. Interestingly, the bilateral giant myelolipoma associated with CAH
      that had high androgen and ACTH levels but lacked MC2R and AR overexpression
      presented a significantly shorter AR allele compared with other tumors. In
      addition, X-chromosome inactivation pattern analysis showed a polyclonal origin
      in all tumors, suggesting a stimulatory effect as the trigger for tumor
      development. CONCLUSION: These findings are the first evidence for MC2R or AR
      overexpression in giant bilateral myelolipomas from poor-compliance CAH patients.

PMID- 24884995
TI  - The delivery of distance education--is it time for doctoral programs in
      gerontology?
AB  - The delivery of higher education in gerontology is changing; students are now
      able to receive an education solely online. Perhaps it is time to consider
      offering this option at the doctoral level. A needs assessment was conducted to
      assess whether a doctoral program in gerontology should be created in the Great
      Plains Interactive Distance Education Alliance (GPIDEA) program. An online survey
      was sent to 247 students enrolled in the GPIDEA program and to students who had
      taken a GPIDEA course in gerontology but were not currently enrolled in the
      program. One hundred and twenty-three students began the survey, although only
      120 students completed the survey. Findings indicated students are interested in
      a doctoral program in gerontology. Approximately 65% of students were interested
      in obtaining a PhD from a distance education program. However, an applied program
      focusing on community outreach and leadership was of most interest to students.
      Students were less interested in research-based programs or in research
      residency. Therefore, the development of distance education doctoral degree
      programs in gerontology may need to be created differently than "traditional"
      formats. 

PMID- 24884996
TI  - Influenza vaccination during pregnancy: a qualitative study of the knowledge,
      attitudes, beliefs, and practices of general practitioners in Central and South
      Western Sydney.
AB  - BACKGROUND: Pregnant women have an increased risk of influenza complications.
      Influenza vaccination during pregnancy is safe and effective, however coverage in
      Australia is less than 40%. Pregnant women who receive a recommendation for
      influenza vaccination from a health care provider are more likely to receive it,
      however the perspectives of Australian general practitioners has not previously
      been reported. The aim of the study was to investigate the knowledge, attitudes,
      beliefs, and practices of general practitioners practicing in South-Western
      Sydney, Australia towards influenza vaccination during pregnancy. METHODS: A
      qualitative descriptive study was conducted, with semi-structured interviews
      completed with seventeen general practitioners in October 2012. A thematic
      analysis was undertaken by four researchers, and transcripts were analysed using
      N-Vivo software according to agreed codes. RESULTS: One-third of the general
      practitioners interviewed did not consider influenza during pregnancy to be a
      serious risk for the mother or the baby. The majority of the general
      practitioners were aware of the government recommendations for influenza
      vaccination during pregnancy, but few general practitioners were confident of
      their knowledge about the vaccine and most felt they needed more information.
      More than half the general practitioners had significant concerns about the
      safety of influenza vaccination during pregnancy. Their practices in the
      provision of the vaccine were related to their perception of risk of influenza
      during pregnancy and their confidence about the safety of the vaccine. While two
      thirds reported that they are recommending influenza vaccination to their
      pregnant patients, many were adopting principles of patient-informed choice in
      their approach and encouraged women to decide for themselves whether they would
      receive the vaccine. CONCLUSIONS: General practitioners have varied knowledge,
      attitudes, and beliefs about influenza vaccination during pregnancy, which
      influence their practices. Addressing these could have a significant impact on
      improving vaccine uptake during pregnancy.

PMID- 24884997
TI  - Utility of telephone survey methods in population-based health studies of older
      adults: an example from the Alberta Older Adult Health Behavior (ALERT) study.
AB  - BACKGROUND: Random digit dialing is often used in public health research
      initiatives to accrue and establish a study sample; however few studies have
      fully described the utility of this approach. The primary objective of this paper
      was to describe the implementation and utility of using random digit dialing and
      Computer Assisted Telephone Interviewing (CATI) for sampling, recruitment and
      data collection in a large population-based study of older adults [Alberta Older
      Adult Health Behavior (ALERT) study]. METHODS: Using random digit dialing, older
      adults (> = 55 years) completed health behavior and outcome and demographic
      measures via CATI. After completing the CATI, participants were invited to
      receive a step pedometer and waist circumference tape measure via mail to gather
      objectively derived ambulatory activity and waist circumference assessments.
      RESULTS: Overall, 36,000 telephone numbers were called of which 7,013 were deemed
      eligible for the study. Of those, 4,913 (70.1%) refused to participate in the
      study and 804 (11.4%) participants were not included due to a variety of call
      dispositions (e.g., difficult to reach, full quota for region). A total of 1,296
      participants completed telephone interviews (18.5% of those eligible and 3.6% of
      all individuals approached). Overall, 22.8% of households did not have an age 55+
      resident and 13.6% of individuals refused to participate, Average age was 66.5
      years, and 43% were male. A total of 1,081 participants (83.4%) also submitted
      self-measured ambulatory activity (i.e., via step pedometer) and anthropometric
      data (i.e., waist circumference). With the exception of income (18.7%), the rate
      of missing data for demographics, health behaviors, and health measures was
      minimal (<1%). CONCLUSIONS: Older adults are willing to participate in telephone
      based health surveys when randomly contacted. Researchers can use this
      information to evaluate the feasibility and the logistics of planned studies
      using a similar population and study design.

PMID- 24884998
TI  - Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder
      symptoms in rats.
AB  - BACKGROUND: Spinal cord injury (SCI) deteriorates various physical functions, in
      particular, bladder problems occur as a result of damage to the spinal cord. Stem
      cell therapy for SCI has been focused as the new strategy to treat the injuries
      and to restore the lost functions. The oral mucosa cells are considered as the
      stem cells-like progenitor cells. In the present study, we investigated the
      effects of oral mucosa stem cells on the SCI-induced neurogenic bladder in
      relation with apoptotic neuronal cell death and cell proliferation. RESULTS: The
      contraction pressure and the contraction time in the urinary bladder were
      increased after induction of SCI, in contrast, transplantation of the oral mucosa
      stem cells decreased the contraction pressure and the contraction time in the SCI
      induced rats. Induction of SCI initiated apoptosis in the spinal cord tissues,
      whereas treatment with the oral mucosa stem cells suppressed the SCI-induced
      apoptosis. Disrupted spinal cord by SCI was improved by transplantation of the
      oral mucosa stem cells, and new tissues were increased around the damaged
      tissues. In addition, transplantation of the oral mucosa stem cells suppressed
      SCI-induced neuronal activation in the voiding centers. CONCLUSIONS:
      Transplantation of oral mucosa stem cells ameliorates the SCI-induced neurogenic
      bladder symptoms by inhibiting apoptosis and by enhancing cell proliferation. As
      the results, SCI-induced neuronal activation in the neuronal voiding centers was
      suppressed, showing the normalization of voiding function.

PMID- 24884999
TI  - Northerners versus southerners: Italian anthropology and psychology faced with
      the "southern question".
AB  - Following the Unification of Italy (1861), when confronted with the
      underdevelopment problems of the south that had given rise to the so-called
      "southern question," some Italian anthropologists and psychologists began to
      study the populations of the south from the psycho-anthropological point of view.
      These scientists, at times subject to preconceived ideas toward the southerners,
      conveyed observations and descriptions of the southern character traits that, in
      general, were considered different, in a negative sense, with respect to those of
      the northern peoples. To explain such diversity in the "psychological"
      characteristics between the north and south of the country (presumed cause also
      of the south's backwardness), various hypotheses were advanced related to the
      kind of heredity theory adopted, which could be of, more or less, an "innatist"
      or "transformist" or "environmentalist" kind. The distinction proposed in this
      article between at least 2 different "hereditarian" theories formulated by the
      Italian scientists, and the confrontation of these theories with the hypotheses
      expressed by the "southernist" sociologists, contrary to the idea of "racial
      varieties" present in the Italian population, allows one to understand in what
      way and in what sense, at the threshold of the 20th century, there arose the
      ideology of "Nordicism" and the roots of racism were planted.

PMID- 24885000
TI  - Clara Harrison Town and the origins of the first institutional commitment law for
      the "feebleminded": psychologists as expert diagnosticians.
AB  - The first law providing for the commitment of "feeble-minded" individuals in the
      United States was passed in 1915, in the state of Illinois. House Bill 655 not
      only allowed for the permanent, involuntary institutionalization of feeble-minded
      individuals, but it shifted the commitment and discharge authority from the
      institution superintendents to the courts. Clara Harrison Town, a student of
      Lightner Witmer, and the state psychologist at the second largest institution for
      feeble-minded individuals in the country, was instrumental in this law passing
      and in ensuring that psychologists, for the first time, be viewed as court
      "experts" when testifying as to the feeble mindedness of individuals.

PMID- 24885001
TI  - Maximal exercise in obese patients with COPD: the role of fat free mass.
AB  - BACKGROUND: Obese patients (OB) with COPD may better tolerate exercise as
      compared to normal weight (NW) COPD patients, even if the reason for this is not
      yet fully understood. We investigated the interactions between obesity, lung
      hyperinflation, fat-free mass (FFM) and exercise capacity in COPD. METHODS: Forty
      four patients (16 females; age 65 +/- 8 yrs) were assessed by resting lung
      function and body composition and exercised on a cycle-ergometer to exhaustion.
      RESULTS: Twenty-two OB and 22 NW patients did not differ in age, gender and
      airflow obstruction degree, but in FFM (p < 0.05). OB had significantly higher
      values in inspiratory capacity/total lung capacity ratio (IC/TLC) at rest (p <
      0.01), but not at peak of exercise and showed significantly higher values in peak
      workload (p < 0.05) and in peak oxygen uptake (VO2), when expressed as absolute
      value (p < 0.05), but not when corrected by FFM. OB compared to NW experienced
      lower leg fatigue (p < 0.05), but similar dyspnea on exertion. In all patients,
      the regression equation by stepwise multiple regression analysis for peak
      workload and VO2, as dependent variables included both FFM and IC/TLC at rest, as
      independent variables (r(2) = 0.43 and 0.37, respectively). CONCLUSIONS: OB with
      COPD, as compared to NW patients matched for age, gender and airflow obstruction,
      had greater FFM and less resting lung hyperinflation and showed greater maximal
      exercise capacity. Pulmonary and non-pulmonary factors may explain the
      preservation of exercise tolerance in patients with COPD associated with obesity.

PMID- 24885002
TI  - Clinical relevance of breast cancer-related genes as potential biomarkers for
      oral squamous cell carcinoma.
AB  - BACKGROUND: Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer
      form with relatively low 5-year survival rates, due partially to late detection
      and lack of complementary molecular markers as targets for treatment. Molecular
      profiling of head and neck cancer has revealed biological similarities with basal
      like breast and lung carcinoma. Recently, we showed that 16 genes were
      consistently altered in invasive breast tumors displaying varying degrees of
      aggressiveness. METHODS: To extend our findings from breast cancer to another
      cancer type with similar characteristics, we performed an integrative analysis of
      transcriptomic and proteomic data to evaluate the prognostic significance of the
      16 putative breast cancer-related biomarkers in OSCC using independent microarray
      datasets and immunohistochemistry. Predictive models for disease-specific (DSS)
      and/or overall survival (OS) were calculated for each marker using Cox
      proportional hazards models. RESULTS: We found that CBX2, SCUBE2, and STK32B
      protein expression were associated with important clinicopathological features
      for OSCC (peritumoral inflammatory infiltration, metastatic spread to the
      cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are
      involved in the hedgehog signaling pathway which plays a pivotal role in
      metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein
      expression were correlated with DSS and OS, respectively. CONCLUSIONS: Taken
      together, these candidates and the hedgehog signaling pathway may be putative
      targets for drug development and clinical management of OSCC patients.

PMID- 24885004
TI  - Protracted primary cytomegalovirus infection presenting as ileoanal pouchitis in
      a non-immunosuppressed patient: a case report.
AB  - INTRODUCTION: Pouchitis often occurs after proctocolectomy and ileal pouch-anal
      anastomosis for ulcerative colitis. It is usually deemed idiopathic and commonly
      responds to antibacterial therapy. To date, only a few cases of cytomegalovirus
      pouchitis have been documented, and only a single report describes pouchitis in a
      case of assumed primary cytomegalovirus infection. CASE PRESENTATION: A 26-year
      old Caucasian woman underwent proctocolectomy and ileal pouch-anal anastomosis
      for refractory ulcerative colitis and adenocarcinoma. After 28 months she
      developed bloody diarrhoea, abdominal pain, fever, nausea and general malaise
      suggesting severe pouchitis. Antibiotic treatment reduced humoral inflammation,
      but failed to resolve her fever. A pouchoscopy revealed distinct pouchitis, and
      cytomegalovirus infection was diagnosed from pouch biopsies by polymerase chain
      reaction as well as conventional histology and immunohistochemistry. The
      infection was confirmed in her blood by polymerase chain reaction and pp65
      antigen test, and was clearly defined as the 'primary' infection by serial
      serological tests. Intravenous treatment with ganciclovir (10mg/kg body
      weight/day) led to resolution of symptoms and negative cytomegalovirus
      deoxyribonucleic acid and pp65 within a few days. When symptoms and laboratory
      evidence of cytomegalovirus infection recurred a few days after completing 20
      days of therapy with ganciclovir and valganciclovir, a second course of
      ganciclovir treatment was initiated. CONCLUSIONS: Cytomegalovirus infection of
      the ileoanal pouch is an important differential diagnosis of pouchitis even in
      non-immunosuppressed patients and can be treated with ganciclovir.

PMID- 24885003
TI  - Current development in genetic engineering strategies of Bacillus species.
AB  - The complete sequencing and annotation of the genomes of industrially-important
      Bacillus species has enhanced our understanding of their properties, and allowed
      advances in genetic manipulations in other Bacillus species. Post-genomic studies
      require simple and highly efficient tools to enable genetic manipulation. Here,
      we summarize the recent progress in genetic engineering strategies for Bacillus
      species. We review the available genetic tools that have been developed in
      Bacillus species, as well as methods developed in other species that may also be
      applicable in Bacillus. Furthermore, we address the limitations and challenges of
      the existing methods, and discuss the future research prospects in developing
      novel and useful tools for genetic modification of Bacillus species. 

PMID- 24885005
TI  - Video-based feedback of oral clinical presentations reduces the anxiety of ICU
      medical students: a multicentre, prospective, randomized study.
AB  - BACKGROUND: Oral presentations of clinical cases by medical students during
      medical rounds in hospital wards are a source of anxiety and little is known
      about how this anxiety can be alleviated. The objective of this study was to
      investigate whether video-based feedback of public oral presentations can reduce
      anxiety in 4th year medical students. METHODS: Multicentre randomized study
      conducted in six intensive care units (ICU) and emergency departments (ED) in
      France over a 9-month period in 2012. One hundred and forty two 4th year medical
      students were randomized to two groups: intervention and control. Students in the
      intervention group were recorded while making an oral presentation of a patient
      during morning ward rounds, followed by video-based feedback. Students in the
      control group conducted presented classical oral presentations without being
      filmed and with no formal feedback. Anxiety levels during a public oral
      presentation were assessed using the Spielberger State Anxiety Inventory (STAI
      S). The primary outcome was the difference in STAI-S scores between groups at the
      beginning and at the end of a 3-month ICU or ED internship. RESULTS: Seventy four
      students were randomized to the 'video-based feedback' group and 68 were
      randomized to the control group. In both groups, STAI-S scores were significantly
      lower after 3 months of internship. However, the reduction in STAI-S scores was
      significantly greater in the "video-based feedback" group than in controls (-9.2
      +/- 9.3 vs. -4.6 +/- 8.2, p = 0.024. Compared to the control group, significantly
      fewer students with high-level anxiety were observed in the "video-based
      feedback" group after 3 months of internship (68 vs. 28%, p <0.001). CONCLUSIONS:
      Compared to "usual practice", video-assisted oral feedback reduced anxiety and
      significantly decreased the proportion of students experiencing severe anxiety.

PMID- 24885006
TI  - Metastatic squamous cell carcinoma from hand skin causing small bowel
      obstruction: an unusual case presentation.
AB  - The small bowel rarely suffers from metastatic tumors from outside the abdomen.
      Small bowel obstructions caused by the metastatic spread of squamous cell
      carcinoma (SCC) of the hand to the intestines are even rarer. A 71-year-old man
      with intermittent abdominal distension and pain for 4 months was diagnosed with
      partial bowel obstruction. The patient underwent a video capsule endoscopic
      examination; however, the patient was unable to pass the capsule, which worsened
      the abdominal distension. He was transferred to our department for acute
      intestinal obstruction, and an emergency exploratory laparotomy was performed.
      Intraoperatively, a tumoral stricture of the intestine at a distance of 150 cm
      from the ileo-cecum and dilation of the proximal bowel was found. The involved
      segment was resected, and ileo-ileal anastomosis was performed. The pathological
      sections confirmed the lesion to be a moderately differentiated SCC with whole
      bowel layer infiltration. Immunohistochemical staining showed positive expression
      of cytokeratin 5/6 and p63. The patient had an uneventful recovery. However, 6
      months later, he was hospitalized again with intestinal obstruction. Reoperation
      was performed and revealed multiple metastases in the small bowel. He died 4
      months later. In this unusual case, metastasizing SCC of the hand skin led to
      intestinal obstruction and poor prognosis. Therefore, follow-up procedures
      regarding intestinal spread should be performed in patients with SCC who present
      with abdominal symptoms. 

PMID- 24885007
TI  - Incidence, histopathologic analysis and distribution of tumours of the hand.
AB  - BACKGROUND: The aim of this large collective and meticulous study of primary bone
      tumours and tumourous lesions of the hand was to enhance the knowledge about
      findings of traumatological radiographs and improve differential diagnosis.
      METHODS: This retrospective study reviewed data collected from 1976 until 2006 in
      our Bone Tumour Registry. The following data was documented: age, sex,
      radiological investigations, tumour location, histopathological features
      including type and dignity of the tumour, and diagnosis. RESULTS: The
      retrospective analysis yielded 631 patients with a mean age of 35.9 +/- 19.2
      years. The majority of primary hand tumours were found in the phalanges (69.7%)
      followed by 24.7% in metacarpals and 5.6% in the carpals. Only 10.6% of all cases
      were malignant. The major lesion type was cartilage derived at 69.1%, followed by
      bone cysts 11.3% and osteogenic tumours 8.7%. The dominant tissue type found in
      phalanges and metacarpals was of cartilage origin. Osteogenic tumours were
      predominant in carpal bones. Enchondroma was the most commonly detected tumour in
      the hand (47.1%). CONCLUSIONS: All primary skeletal tumours can be found in the
      hand and are most often of cartilage origin followed by bone cysts and osteogenic
      tumours. This study furthermore raises awareness about uncommon or rare tumours
      and helps clinicians to establish proper differential diagnosis, as the majority
      of detected tumours of the hand are asymptomatic and accidental findings on
      radiographs.

PMID- 24885008
TI  - The role of deleterious mutations in the stability of hybridogenetic water frog
      complexes.
AB  - BACKGROUND: Some species of water frogs originated from hybridization between
      different species. Such hybrid populations have a particular reproduction system
      called hybridogenesis. In this paper we consider the two species Pelophylax
      ridibundus and Pelophylax lessonae, and their hybrids Pelophylax esculentus. P.
      lessonae and P. esculentus form stable complexes (L-E complexes) in which P.
      esculentus are hemiclonal. In L-E complexes all the transmitted genomes by P.
      esculentus carry deleterious mutations which are lethal in homozygosity. RESULTS:
      We analyze, by means of an individual based computational model, L-E complexes.
      The results of simulations based on the model show that, by eliminating
      deleterious mutations, L-E complexes collapse. In addition, simulations show that
      particular female preferences can contribute to the diffusion of deleterious
      mutations among all P. esculentus frogs. Finally, simulations show how L-E
      complexes react to the introduction of translocated P. ridibundus. CONCLUSIONS:
      The conclusions are the following: (i) deleterious mutations (combined with
      sexual preferences) strongly contribute to the stability of L-E complexes; (ii)
      female sexual choice can contribute to the diffusion of deleterious mutations;
      and (iii) the introduction of P. ridibundus can destabilize L-E complexes.

PMID- 24885010
TI  - Effects of Gelam and Acacia honey acute administration on some biochemical
      parameters of Sprague Dawley rats.
AB  - BACKGROUND: Since ancient times, honey has been used for medicinal purposes in
      many cultures; it is one of the oldest and most enduring substances used in wound
      management. Scientific evidence for its efficacy is widely studied, but systemic
      safety studies are still lacking. It is essential to study the impact of
      consumption of honey on the health and proper development of the consumer.
      Therefore, the present study was designed to observe the effects of acute
      administration (14 days) of Gelam honey (GH), a wild harvesting honey and Acacia
      honey (AH), a beekeeping honey, on male and female Sprague Dawley (SD) rats.
      METHODS: An acute oral study was performed following OECD test guideline 423,
      with minor modifications. In the study, GH, AH and sucrose (S) were administered
      at 2000 mg/kg body weight. Animals were observed for the next 14 days. Gross
      pathology was performed at the end of the study. Animals were observed for
      mortality, morbidity, body weight changes, feed and water intake. Clinical
      biochemistry, gross pathology, relative organ weight and histopathological
      examination were performed. RESULTS: Rats fed with honey did not exhibit any
      abnormal signs or deaths. Results showed a decrease in weight gain and energy
      efficiency, but significantly increased in total food intake and total calories
      in female rats fed with GH, compared to control (p<0.05). Nevertheless, a
      significant increase in body weight was observed in male rats in all honey
      treated groups. Male rats fed with AH significantly decreased in total food
      intake, total calories and energy efficiency. Both male and female rats fed with
      GH displayed a significant decrease in triglycerides compared to control group.
      Hepatic and renal function levels were within acceptable range. The gross
      necropsy analysis did not reveal changes in any of the organs examined.
      CONCLUSIONS: Our results suggest that acute consumption of GH and AH at 2000
      mg/kg body weight of male and female SD rats has some discrepancy effects on
      biochemical parameters but in line with OECD regulation. Gelam honey may have
      potential in controlling weight gain and triglyceride levels in female rats
      compared to Acacia honey. SD rats have some effect on biochemical parameters, an
      exploration of which would make for intriguing analysis.

PMID- 24885011
TI  - Human Papillomavirus 16, 18, 31 and 45 viral load, integration and methylation
      status stratified by cervical disease stage.
AB  - BACKGROUND: Persistent infection with oncogenic Human Papillomavirus (HPV) is
      associated with the development of cervical cancer with each genotype differing
      in their relative contribution to the prevalence of cervical disease. HPV DNA
      testing offers improved sensitivity over cytology testing alone but is
      accompanied by a generally low specificity. Potential molecular markers of
      cervical disease include type-specific viral load (VL), integration of HPV DNA
      into the host genome and methylation of the HPV genome. The aim of this study was
      to evaluate the relationship between HPV type-specific viral load, integration
      and methylation status and cervical disease stage in samples harboring HPV16,
      HPV18, HPV31 or HPV45. METHODS: Samples singly infected with HPV16 (n=226), HPV18
      (n=32), HPV31 (n=75) or HPV45 (n=29) were selected from a cohort of 4,719 women
      attending cervical screening in England. Viral load and integration status were
      determined by real-time PCR while 3'L1-URR methylation status was determined by
      pyrosequencing or sequencing of multiple clones derived from each sample.
      RESULTS: Viral load could differentiate between normal and abnormal cytology with
      a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2
      26.1; p<0.001) with some variation between genotypes. Viral integration was
      poorly associated with cervical disease. Few samples had fully integrated genomes
      and these could be found throughout the course of disease. Overall, integration
      status could distinguish between normal and abnormal cytology with a sensitivity
      of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0-6.8; p=0.054). Methylation
      levels were able to differentiate normal and low grade cytology from high grade
      cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8
      18.0; p<0.001). However, methylation varied widely between genotypes with HPV18
      and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG
      sites than HPV16 and HPV31. CONCLUSIONS: This study lends support for HPV viral
      load and CpG methylation status, but not integration status, to be considered as
      potential biomarkers of cervical disease.

PMID- 24885009
TI  - The nuclear receptor gene family in the Pacific oyster, Crassostrea gigas,
      contains a novel subfamily group.
AB  - BACKGROUND: Nuclear receptors are a superfamily of transcription factors
      important in key biological, developmental and reproductive processes. Several of
      these receptors are ligand- activated and through their ability to bind
      endogenous and exogenous ligands, are potentially vulnerable to xenobiotics.
      Molluscs are key ecological species in defining aquatic and terrestrial habitats
      and are sensitive to xenobiotic compounds in the environment. However, the
      understanding of nuclear receptor presence, function and xenobiotic disruption in
      the phylum Mollusca is limited. RESULTS: Here, forty-three nuclear receptor
      sequences were mined from the genome of the Pacific oyster, Crassostrea gigas.
      They include members of NR0-NR5 subfamilies, notably lacking any NR6 members.
      Phylogenetic analyses of the oyster nuclear receptors have been conducted showing
      the presence of a large novel subfamily group not previously reported, which is
      named NR1P. Homologues to all previous identified nuclear receptors in other
      mollusc species have also been determined including the putative heterodimer
      partner retinoid X receptor, estrogen receptor and estrogen related receptor.
      CONCLUSION: C. gigas contains a highly diverse set of nuclear receptors including
      a novel NR1 group, which provides important information on presence and evolution
      of this transcription factor superfamily in invertebrates. The Pacific oyster
      possesses two members of NR3, the sex steroid hormone receptor analogues, of
      which there are 9 in humans. This provides increasing evidence that steroid
      ligand specific expansion of this family is deuterostome specific. This new
      knowledge on divergence and emergence of nuclear receptors in C. gigas provides
      essential information for studying regulation of molluscan gene expression and
      the potential effects of xenobiotics.

PMID- 24885012
TI  - Newborn pig trachea cell line cultured in air-liquid interface conditions allows
      a partial in vitro representation of the porcine upper airway tissue.
AB  - BACKGROUND: The domestic pig is an excellent animal model to study human
      microbial diseases due to its similarity to humans in terms of anatomy,
      physiology, and genetics. We assessed the suitability of an in vitro air-liquid
      interface (ALI) culture system for newborn pig trachea (NPTr) cells as a
      practical tool for analyzing the immune response of respiratory epithelial cells
      to aggressors. This cell line offers a wide microbial susceptibility spectrum to
      both viruses and bacteria. The purpose of our study was to evaluate and
      characterize diverse aspects of cell differentiation using different culture
      media. After the NPTr cells reached confluence, the apical medium was removed and
      the cells were fed by medium from the basal side. RESULTS: We assessed the
      cellular layer's capacity to polarize and differentiate in ALI conditions. Using
      immunofluorescence and electronic microscopy we evaluated the presence of goblet
      and ciliated cells, the epithelial junction organization, and the transepithelial
      electrical resistance. We found that the cellular layer develops a variable
      density of mucus producing cells and acquires a transepithelial resistance. We
      also identified increased development of cellular junctions over the culture
      period. Finally, we observed variable expression of transcripts associated to
      proteins such as keratin 8, mucins (MUC1, MUC2, and MUC4), occludin, and villin
      1. CONCLUSIONS: The culture of NPTr cells in ALI conditions allows a partial in
      vitro representation of porcine upper airway tissue that could be used to
      investigate some aspects of host/respiratory pathogen interactions.

PMID- 24885013
TI  - Apolipoprotein E gene epsilon4epsilon4 is associated with elevated risk of
      primary open angle glaucoma in Asians: a meta-analysis.
AB  - BACKGROUND: Epidemiological studies have evaluated the association between
      Apolipoprotein E (APOE) gene epsilon2/epsilon3/epsilon4 polymorphism and glaucoma
      susceptibility. However, the published data are still inconclusive. The aim of
      the present study is to evaluate the impact of APOE gene
      epsilon2/epsilon3/epsilon4 polymorphism on glaucoma risk by using meta-analysis.
      METHODS: A comprehensive literature search of PubMed, EMBASE, Cochrane, Elsevier
      Science Direct and CNKI databases was conducted to identify relevant articles,
      with the last report up to January 5, 2014. Pooled odds ratio (OR) and 95%
      confidence interval (CI) were used to assess the strength of association by using
      the fixed or random effect model. RESULTS: Fifteen separate studies including
      2,700 cases and 2,365 controls were included in the meta-analysis. We did not
      detect a significant association between APOE gene epsilon2/epsilon3/epsilon4
      polymorphism and glaucoma in overall population (P > 0.0083). In Asians, we
      detected an association of the epsilon4epsilon4 genotype with elevated risk for
      glaucoma (OR = 5.22, 95% CI = 1.85-14.68, P = 0.002), mainly for primary open
      angle glaucoma (OR = 4.98, 95% CI = 1.75-14.20, P = 0.003). CONCLUSIONS: The meta
      analysis suggests that APOE gene epsilon4epsilon4 may be associated with elevated
      risk for primary open angle glaucoma in Asians. However, more epidemiologic
      studies based on larger sample size, case-control design and stratified by
      ethnicity as well as types of glaucoma are suggested to further clarify the
      relationship between APOE gene epsilon2/epsilon3/epsilon4 polymorphism and
      genetic predisposition to glaucoma.

PMID- 24885014
TI  - 8-Methyltryptanthrin-induced differentiation of P19CL6 embryonal carcinoma cells
      into spontaneously beating cardiomyocyte-like cells.
AB  - Enhancement of cardiac differentiation is critical to stem cell transplantation
      therapy for severe ischemic heart disease. The aim of this study was to
      investigate whether several derivatives of tryptanthrin (1), extracted from the
      medicinal plant Polygonum tinctorium, induce the differentiation of P19CL6 mouse
      embryonal carcinoma cells into beating cardiomyocyte-like cells. P19CL6 cells
      were cultured in alpha-MEM supplemented with 10% FBS including a test compound or
      vehicle. Drug-induced differentiation was assessed by measuring the number of
      beating and nonbeating aggregates and the area of beating aggregates, and the
      expression of genes involved in cardiac differentiation was evaluated by real
      time PCR. A 1 MUM concentration of 8-methyltryptanthrin (2) induced the
      differentiation of P19CL6 cells into cardiomyocyte-like cells to a significantly
      greater degree than 1% dimethyl sulfoxide (DMSO), a conventional differentiation
      inducer of P19CL6 cells. Furthermore, 2 strongly increased both the number and
      the area of spontaneously beating aggregates in comparison with DMSO. Two
      distinct genes of the calcium channel family, Cav1.2 and Cav3.1, underlying
      cardiac automaticity were significantly expressed in the presence of 2. Gap
      junction genes GJA1 and GJA5 contributing to the synchronized contraction of the
      myocardium were also induced significantly by 2. These results suggest that 2
      successfully differentiated P19CL6 cells into spontaneously beating cardiomyocyte
      like cells by activating the gene expression of pacemaker channels and gap
      junctions. 

PMID- 24885015
TI  - Clinical and mutational features of Vietnamese children with X-linked
      agammaglobulinemia.
AB  - BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immune deficiency
      characterized by recurrent bacterial infections and profoundly depressed serum
      immunoglobulin levels and circulating mature B cells. It is caused by mutations
      of the Bruton tyrosine kinase (BTK) gene and is the most common form of inherited
      antibody deficiency. To our knowledge, this is the first report of XLA from
      Vietnam. METHODS: We investigated the BTK gene mutations and clinical features of
      four unrelated Vietnamese children. RESULTS: The mean ages at onset and at
      diagnosis were 2.5 and 8 years, respectively. All patients had a medical history
      of otitis media, pneumonia, and septicemia at the time of diagnosis. Other
      infections reported included sinusitis, bronchiectasis, arthritis, skin
      infections, meningitis, and recurrent diarrhea. We identified one previously
      reported mutation (c.441G >A) and three novel mutations: two frameshifts
      (c.1770delG and c.1742 delG), and one nonsense (c.1249A >T). CONCLUSIONS: The
      delayed diagnosis may be attributable to insufficient awareness of this rare
      disease on the background of frequent infections even in the immunocompetent
      pediatric population in Vietnam. Our results further support the importance of
      molecular genetic testing in diagnosis of XLA.

PMID- 24885016
TI  - Properdin has an ascendancy over factor H regulation in complement-mediated renal
      tubular damage.
AB  - BACKGROUND: Urinary (U)-complement components have been detected in patients with
      proteinuric renal diseases, and complement activation via the alternative pathway
      (AP) is believed to play a role in renal tubular damage. The present study aimed
      to examine the regulation of complement AP activation in patients with renal
      tubular damage by focusing on the balance between properdin (P) and factor H
      (fH). METHODS: In the in vivo studies, U concentrations of P, fH and membrane
      attack complex (MAC) were measured in patients with renal diseases using an
      enzyme-linked immunosorbent assay (ELISA), and their relationships with the
      clinical data were evaluated. In the in vitro studies, human proximal tubular
      epithelial cells (PTECs) were incubated with normal human serum (NHS), P-depleted
      serum (PDS), purified P and/or fH. Changes in cell morphology and phenotype were
      assessed by microscopy, real-time polymerase chain reaction (PCR), immunostaining
      and a cell viability assay. RESULTS: The U-P, fH and MAC concentrations were
      significantly higher in patients with renal disease than in normal controls and
      correlated with the U-protein and tubular damage markers. Furthermore,
      multivariate analysis revealed a relationship between P levels and tubular damage
      markers. There were no significant changes in morphology and mRNA expression in
      the AP components (P, fH, fB, C3, C5 and C9) after the addition of up to 25% NHS.
      Dose-dependent depositions of P or fH were observed after the addition of P or fH
      on PTECs. Depositions of P were not inhibited by fH in a mixture of a fixed
      concentration of P and a variable concentration of fH, and vice versa.
      Preincubation with the fixed concentration of P before the addition of NHS or PDS
      increased the depositions of P, C3 and MAC compared with incubation with intact
      NHS or intact PDS only; the depositions of C3 and MAC showed a serum-dependent
      trend. Preincubation with P before NHS addition significantly suppressed cell
      viability without causing morphological changes. CONCLUSIONS: In the pathogenesis
      of renal tubular damage, P can directly bind to PTECs and may accelerate AP
      activation by surpassing fH regulation.

PMID- 24885017
TI  - Comparing the EQ-5D 3L and 5L: measurement properties and association with
      chronic conditions and multimorbidity in the general population.
AB  - BACKGROUND: Studies comparing the measurement properties of EQ-5D 3L (3L) and EQ
      5D 5L (5L) are limited to specific patient populations with small sample sizes.
      Using a general population sample, we compared 3L and 5L in terms of their
      measurement properties and association with number of chronic conditions,
      including multimorbidity--the concurrent occurrence of two or more chronic
      conditions. METHODS: Data were available from two consecutive cycles of a cross
      sectional telephone interview survey using 3L (2010 cycle) and 5L (2012 cycle),
      in the general population of adults (age >= 18 years) in Alberta, Canada.
      Measurement properties were compared by determining their feasibility, ceiling
      effect, and discriminatory power (Shannon indices) for 3L and 5L. Linear
      regression models were fitted to test the associations between multimorbidity and
      EQ-5D index score. RESULTS: Data were available for 4946 (2010) and 4752 (2012)
      survey respondents with information on HRQL. Compared to 3L, 5L showed lower
      ceiling effect (32.3% versus 42.1%), higher absolute discriminatory power
      (Shannon index, mean 0.79 versus 0.52) and higher relative discriminatory power
      (Shannon Evenness index, mean 0.09 versus 0.06 for 3L). Despite these
      differences, similar relationships of lower HRQL with greater multimorbidity were
      observed for the 3L (beta = -0.13, 95% CI -0.15; -0.11) and 5L (beta = -0.12, 95%
      CI -0.13; -0.11). CONCLUSIONS: Using a general population sample, the EQ-5D 5L
      showed better measurement properties than the EQ-5D 3L. Nonetheless, clinically
      important differences in HRQL associated with multimorbidity were similar in
      magnitude using both versions of EQ-5D.

PMID- 24885018
TI  - Improving rheumatic fever surveillance in New Zealand: results of a surveillance
      sector review.
AB  - BACKGROUND: The New Zealand (NZ) Government has made a strong commitment to
      reduce the incidence of rheumatic fever (RF) by two thirds, to 1.4 cases per
      100,000, by mid-2017. We reviewed the NZ RF surveillance sector, aiming to
      identify potential improvements which would support optimal RF control and
      prevention activities. METHODS: This review used a recently developed
      surveillance sector review method. Interviews with 36 key informants were used to
      describe the sector, assess it and identify its gaps. Priorities for improvement
      and implementation strategies were determined following discussion with these key
      informants, with policy advisors and within the research team. RESULTS: Key
      improvements identified included the need for a comprehensive RF surveillance
      strategy, integrated reporting and an online national RF register. At a
      managerial level this review provided evidence for system change and built
      support for this across the surveillance sector. CONCLUSIONS: The surveillance
      sector review approach can be added to the small set of tools currently available
      for developing and evaluating surveillance systems. This new approach is likely
      to prove useful as we confront the challenges of combating new emerging
      infectious diseases, responding to global environmental changes, and reducing
      health inequalities.

PMID- 24885019
TI  - Genomic regions involved in yield potential detected by genome-wide association
      analysis in Japanese high-yielding rice cultivars.
AB  - BACKGROUND: High-yielding cultivars of rice (Oryza sativa L.) have been developed
      in Japan from crosses between overseas indica and domestic japonica cultivars.
      Recently, next-generation sequencing technology and high-throughput genotyping
      systems have shown many single-nucleotide polymorphisms (SNPs) that are proving
      useful for detailed analysis of genome composition. These SNPs can be used in
      genome-wide association studies to detect candidate genome regions associated
      with economically important traits. In this study, we used a custom SNP set to
      identify introgressed chromosomal regions in a set of high-yielding Japanese rice
      cultivars, and we performed an association study to identify genome regions
      associated with yield. RESULTS: An informative set of 1152 SNPs was established
      by screening 14 high-yielding or primary ancestral cultivars for 5760 validated
      SNPs. Analysis of the population structure of high-yielding cultivars showed
      three genome types: japonica-type, indica-type and a mixture of the two. SNP
      allele frequencies showed several regions derived predominantly from one of the
      two parental genome types. Distinct regions skewed for the presence of parental
      alleles were observed on chromosomes 1, 2, 7, 8, 11 and 12 (indica) and on
      chromosomes 1, 2 and 6 (japonica). A possible relationship between these
      introgressed regions and six yield traits (blast susceptibility, heading date,
      length of unhusked seeds, number of panicles, surface area of unhusked seeds and
      1000-grain weight) was detected in eight genome regions dominated by alleles of
      one parental origin. Two of these regions were near Ghd7, a heading date locus,
      and Pi-ta, a blast resistance locus. The allele types (i.e., japonica or indica)
      of significant SNPs coincided with those previously reported for candidate genes
      Ghd7 and Pi-ta. CONCLUSIONS: Introgression breeding is an established strategy
      for the accumulation of QTLs and genes controlling high yield. Our custom SNP set
      is an effective tool for the identification of introgressed genome regions from a
      particular genetic background. This study demonstrates that changes in genome
      structure occurred during artificial selection for high yield, and provides
      information on several genomic regions associated with yield performance.

PMID- 24885020
TI  - The general status of patients and limited physical activity as risk factors of
      Methicillin-resistant Staphylococcus aureus occurrence in long-term care
      facilities residents in Krakow, Poland.
AB  - BACKGROUND: The aim of this study was to investigate the epidemiology and
      resistance of methicillin-resistant Staphylococcus aureus (MRSA) isolates from
      long-term care facilities (LTCF) residents and to analyze the potential risk
      factors for MRSA occurrence, defined as MRSA colonization and/or infection.
      METHODS: Point prevalence (PPS) and prospective incidence continuous study (CS)
      was carried out on a group of 193 residents in 2009-2010. RESULTS: Overall MRSA
      occurred (with or without infection) among 17.6% of residents. There was 16 cases
      of infections with SA aetiology, of which 10 (58.8%) were caused by MRSA. The
      MRSA prevalence in PPS was 12.9%, in CS infection incidence rate was 5.2%.
      Factors associated with MRSA occurrence were: general status of patients, limited
      physical activity, wound infections (odds ratio, OR 4.6), ulcers in PPS (OR 2.1),
      diabetes (OR 1.6), urinary catheterization (OR 1.6) and stool incontinence (OR
      1.2). CONCLUSIONS: Our data indicate a need for screening of MRSA before
      hospitalization or transfer to rehabilitation centres, especially in a group of
      residents with limitations in physical activity - i.e. with the highest risk of
      MRSA. Results also suggest the need for contact precautions in patients with high
      risk of MRSA occurrence, only. Focus on the high-risk population might be a
      solution for the cost-effective surveillance.

PMID- 24885021
TI  - suPAR and Team Nephrology.
AB  - Primary focal segmental glomerulosclerosis (FSGS) accounts for nearly 10 % of
      patients who require renal replacement therapy. Elevated circulating levels of
      soluble urokinase receptor (suPAR) have been identified as a biomarker to
      discriminate primary FSGS from other glomerulopathies. Subsequent reports have
      questioned the diagnostic utility of this test. In a study in BMC Medicine, Huang
      et al. demonstrate that urinary soluble urokinase receptor (suPAR) excretion
      assists in distinguishing primary FSGS from other glomerular diseases, and that
      high plasma suPAR concentrations are not directly linked to a decline in
      glomerular filtration rate (GFR). This observation suggests that further
      investigation of suPAR is warranted in patients with FSGS. It should be
      interpreted in light of a recent report that B7-1 is expressed in the podocytes
      of a subset of patients with FSGS, and that blocking this molecule may represent
      the first successful targeted intervention for this disease. These advances
      highlight the rapid pace of scientific progress in the field of nephrology.
      Nephrologists should work together, share resources, and expedite the design of
      protocols to evaluate these novel biomarkers in a comprehensive and
      scientifically valid manner.

PMID- 24885023
TI  - Crystallization of confined water pools with radii greater than 1 nm in AOT
      reverse micelles.
AB  - Freezing of water pools inside aerosol sodium bis(2-ethylhexyl) sulfosuccinate
      (AOT) reverse micelles has been investigated. Previous freezing experiments
      suffer from collision and fusion of AOT micelles and resultant loss of water from
      the water pool by shedding out during the cooling process. These phenomena have
      restricted the formation of ice to only when the radius of the water pool (Rw) is
      below 1 nm, and only amorphous ice has been observed. To overcome the size
      limitation, a combination of rapid cooling and a custom-made cell allowing thin
      sample loading is applied for instantaneous and homogeneous freezing. The
      freezing process is monitored with attenuated total reflection infrared
      spectroscopy (ATR-IR) measurements. A cooling rate of ca. -100 K/min and a sample
      thickness of ca. 50 MUm overcomes the limitations mentioned above and allows the
      crystallization of water pools with larger radii (Rw > 1 nm). The corresponding
      ATR-IR spectra of the frozen water pools with Rw < 2.0 nm show similar features
      to the spectrum of metastable cubic ice (Ic). Further increase of the radius of
      the water pool (Rw > 2.0 nm), unfortunately, drastically decreased the integrated
      area of the nu(OH) band observed just after freezing, indicating the breakup of
      the micellar structure and shedding out of the water pool. In addition, it was
      revealed that Ic ice can also be formed in flexible organic self-assembled AOT
      reverse micelles for at least Rw <= ca. 2 nm, as well as in inorganic and solid
      materials with a pore radius of ca. 2 nm. The dependence of the phase transition
      temperature on the curvature of the reverse micelles is discussed from the
      viewpoint of the Gibbs-Thomson effect. 

PMID- 24885022
TI  - Estrogen receptor alpha and aryl hydrocarbon receptor independent growth
      inhibitory effects of aminoflavone in breast cancer cells.
AB  - BACKGROUND: Numerous studies have implicated the aryl hydrocarbon receptor (AhR)
      as a potential therapeutic target for several human diseases, including estrogen
      receptor alpha (ERalpha) positive breast cancer. Aminoflavone (AF), an activator
      of AhR signaling, is currently undergoing clinical evaluation for the treatment
      of solid tumors. Of particular interest is the potential treatment of triple
      negative breast cancers (TNBC), which are typically more aggressive and
      characterized by poorer outcomes. Here, we examined AF's effects on two TNBC cell
      lines and the role of AhR signaling in AF sensitivity in these model cell lines.
      METHODS: AF sensitivity in MDA-MB-468 and Cal51 was examined using cell counting
      assays to determine growth inhibition (GI50) values. Luciferase assays and qPCR
      of AhR target genes cytochrome P450 (CYP) 1A1 and 1B1 were used to confirm AF
      mediated AhR signaling. The requirement of endogenous levels of AhR and AhR
      signaling for AF sensitivity was examined in MDA-MB-468 and Cal51 cells stably
      harboring inducible shRNA for AhR. The mechanism of AF-mediated growth inhibition
      was explored using flow cytometry for markers of DNA damage and apoptosis, cell
      cycle analysis, and beta-galactosidase staining for senescence. Luciferase data
      was analyzed using Student's T test. Three-parameter nonlinear regression was
      performed for cell counting assays. RESULTS: Here, we report that ERalpha
      negative TNBC cell lines MDA-MB-468 and Cal51 are sensitive to AF. Further, we
      presented evidence suggesting that neither endogenous AhR expression levels nor
      downstream induction of AhR target genes CYP1A1 and CYP1B1 is required for AF
      mediated growth inhibition in these cells. Between these two ERalpha negative
      cell lines, we showed that the mechanism of AF action differs slightly. Low dose
      AF mediated DNA damage, S-phase arrest and apoptosis in MDA-MB-468 cells, while
      it resulted in DNA damage, S-phase arrest and cellular senescence in Cal51 cells.
      CONCLUSIONS: Overall, this work provides evidence against the simplified view of
      AF sensitivity, and suggests that AF could mediate growth inhibitory effects in
      ERalpha-positive and negative breast cancer cells, as well as cells with impaired
      AhR expression and signaling. While AF could have therapeutic effects on broader
      subtypes of breast cancer, the mechanism of cytotoxicity is complex, and likely,
      cell line- and tumor-specific.

PMID- 24885024
TI  - Atypical presentation of carcinoid tumor with unresolved right shoulder pain: a
      case report.
AB  - INTRODUCTION: Carcinoid tumors are variants of neuroendocrine tumors that
      typically arise from the gastrointestinal tract and the bronchus, but they can
      involve any organ. Unresolved right shoulder pain manifesting as the first
      clinical presentation of carcinoid tumor with unknown primary origin is a rare
      clinical entity. To the best of our knowledge, herein we present the first case
      report describing metastasis to the right shoulder joint in a patient who
      presented with bone pain as the first clinical manifestation of metastatic
      carcinoid tumor of unknown primary origin. Metastasis to the right scapula as the
      first presentation of an underlying carcinoid tumor in the primary bronchus has
      been reported previously. CASE PRESENTATION: A 72-year-old Caucasian woman
      presented with pain in her right shoulder after a fall. She delayed seeking
      medical attention for 4 weeks for personal reasons. Her physical examination
      revealed no erythema or swelling of the right shoulder. However, tenderness was
      noted on the right subacromial bursa and the right acromioclavicular joint. Her
      drop arm test was positive. An X-ray of the right upper extremity showed no
      fracture. She did not respond to methylprednisolone injections or physical
      therapy. Because of the unresolved right shoulder pain with disturbance of her
      daily activities, magnetic resonance imaging of the right shoulder was ordered,
      which revealed permeative destruction of the right scapula. Because the
      permeative destruction of the bone could have been an osteolytic malignant
      feature, positron emission tomography-computed tomography was performed, which
      produced a scan showing osseous metastasis to the right scapula, multiple liver
      metastases and a 1.7 cm right-lower-lobe pulmonary nodule. Her serotonin and
      chromogranin A levels were significantly elevated. The patient was treated with
      palliative cisplatin and etoposide chemotherapy followed by locoregional
      treatments for metastatic carcinoid tumor. She had mild improvement in her right
      shoulder pain, as well as better range of motion and improved quality of life,
      before she died less than 2 years after her diagnosis. CONCLUSION: Our present
      case report emphasizes the protean manifestations of carcinoid tumors with the
      importance of early diagnosis of bone metastases from these tumors, because early
      diagnosis plays a major role in choosing the therapeutic regimen and
      prognosticating the course of the disease. The treatment goals for high-grade,
      poorly differentiated carcinoid tumors of unknown origin are decreasing the tumor
      load while controlling symptoms with chemotherapy and local modality treatments.

PMID- 24885025
TI  - Finished sequence and assembly of the DUF1220-rich 1q21 region using a haploid
      human genome.
AB  - BACKGROUND: Although the reference human genome sequence was declared finished in
      2003, some regions of the genome remain incomplete due to their complex
      architecture. One such region, 1q21.1-q21.2, is of increasing interest due to its
      relevance to human disease and evolution. Elucidation of the exact variants
      behind these associations has been hampered by the repetitive nature of the
      region and its incomplete assembly. This region also contains 238 of the 270
      human DUF1220 protein domains, which are implicated in human brain evolution and
      neurodevelopment. Additionally, examinations of this protein domain have been
      challenging due to the incomplete 1q21 build. To address these problems, a single
      haplotype hydatidiform mole BAC library (CHORI-17) was used to produce the first
      complete sequence of the 1q21.1-q21.2 region. RESULTS: We found and addressed
      several inaccuracies in the GRCh37sequence of the 1q21 region on large and small
      scales, including genomic rearrangements and inversions, and incorrect gene copy
      number estimates and assemblies. The DUF1220-encoding NBPF genes required the
      most corrections, with 3 genes removed, 2 genes reassigned to the 1p11.2 region,
      8 genes requiring assembly corrections for DUF1220 domains (~91 DUF1220 domains
      were misassigned), and multiple instances of nucleotide changes that reassigned
      the domain to a different DUF1220 subtype. These corrections resulted in an
      overall increase in DUF1220 copy number, yielding a haploid total of 289 copies.
      Approximately 20 of these new DUF1220 copies were the result of a segmental
      duplication from 1q21.2 to 1p11.2 that included two NBPF genes. Interestingly,
      this duplication may have been the catalyst for the evolutionarily important
      human lineage-specific chromosome 1 pericentric inversion. CONCLUSIONS: Through
      the hydatidiform mole genome sequencing effort, the 1q21.1-q21.2 region is
      complete and misassemblies involving inter- and intra-region duplications have
      been resolved. The availability of this single haploid sequence path will aid in
      the investigation of many genetic diseases linked to 1q21, including several
      associated with DUF1220 copy number variations. Finally, the corrected sequence
      identified a recent segmental duplication that added 20 additional DUF1220 copies
      to the human genome, and may have facilitated the chromosome 1 pericentric
      inversion that is among the most notable human-specific genomic landmarks.

PMID- 24885026
TI  - Schmallenberg virus antibody persistence in adult cattle after natural infection
      and decay of maternal antibodies in calves.
AB  - BACKGROUND: Schmallenberg virus (SBV) has swept through the major part of Europe
      in the period 2011-2013. A vaccine against SBV has been developed and may be a
      possible preventive instrument against infection. Presently, there is no data
      available to refute the assumption that natural SBV infection results in long
      term immunity. In that respect, it is of interest to know how long (protecting)
      virus-neutralizing antibodies are present in naturally infected animals. New-born
      calves acquire passive immunity from their dams by ingestion and absorption of
      antibodies present in colostrum, which can block the production of serum
      antibodies when vaccine is administered to calves with maternally derived
      antibodies. In that respect, it is useful to know how long it takes for maternal
      antibodies against SBV to disappear in young animals born from infected dams.
      RESULTS: Longitudinal whole-herd serological monitoring using virus
      neutralization test (VNT) indicated that 80% of adult dairy cows still had
      measurable antibodies against SBV at least 24 months after the estimated
      introduction of the virus into the herd. Median 2Log VNT titer of the adult dairy
      cows (>=1 year) dropped from 8.6 to 5.6 in a period of 17 months. Median 2Log VNT
      maternal antibodies titers of calves sampled within 30 days after birth was 8.
      Calves lost their maternally-derived antibodies after 5-6 months. There was a
      definite positive relationship between the VNT titer of the dam and the VNT titer
      of the corresponding calf (age <= 30 days) of dam-calf combinations sampled on
      the same day: the higher the VNT titer of the dam, the higher the VNT titer
      (maternal antibodies) of the calf. CONCLUSIONS: Our field data support the
      assumption that natural SBV infection in adult cows results in persistence of
      specific antibodies for at least two years. Based on the observed decay of
      maternally-derived antibodies in calves, it is presumed safe to vaccinate calves
      against SBV at an age of approximately 6 months.

PMID- 24885027
TI  - An international survey of pain in adolescents.
AB  - BACKGROUND: A common belief is that pain is uncommon and short lived in
      adolescents. However, the burden of pain in adolescents is unclear because of
      limitations in previous research. The aim of this study is to estimate the
      prevalence of headache, stomach-ache and backache in adolescents and to explore
      the extent to which these three forms of pain coexist based upon a representative
      sample of adolescents from 28 countries. METHODS: Data were analysed from three
      consecutive waves (1997/98, 2001/02 and 2005/06) of the Health Behavior in School
      aged Children: WHO Collaborative Cross-National survey (HBSC). Prevalence
      estimates are based upon adolescents who reported experiencing headache, stomach
      ache or backache at least monthly for the last 6 months. RESULTS: There were a
      total of 404,206 participants with a mean (+/-SD) age of 13.6 (+/-1.7) years
      (range 9.8 to 17.3 years). The prevalence of headache was 54.1%, stomach-ache
      49.8%, backache 37%, and at least one of the three pains 74.4%. Girls had a
      higher prevalence of the three pains than boys and the prevalence of pain
      increased with age. Headache, stomach-ache and backache frequently coexist, for
      example, of those with headache: 21.2% had headache alone, 31% suffered from both
      headache and stomach-ache, 12.1% suffered from backache and headache, and 35.7%
      had all three pains. CONCLUSIONS: Somatic pain is very common in adolescents,
      more often coexisting than occurring in isolation. Our data supports the need for
      further research to improve the understanding of these pains in adolescents.

PMID- 24885028
TI  - Sequence artefacts in a prospective series of formalin-fixed tumours tested for
      mutations in hotspot regions by massively parallel sequencing.
AB  - BACKGROUND: Clinical specimens undergoing diagnostic molecular pathology testing
      are fixed in formalin due to the necessity for detailed morphological assessment.
      However, formalin fixation can cause major issues with molecular testing, as it
      causes DNA damage such as fragmentation and non-reproducible sequencing artefacts
      after PCR amplification. In the context of massively parallel sequencing (MPS),
      distinguishing true low frequency variants from sequencing artefacts remains
      challenging. The prevalence of formalin-induced DNA damage and its impact on
      molecular testing and clinical genomics remains poorly understood. METHODS: The
      Cancer 2015 study is a population-based cancer cohort used to assess the
      feasibility of mutational screening using MPS in cancer patients from Victoria,
      Australia. While blocks were formalin-fixed and paraffin-embedded in different
      anatomical pathology laboratories, they were centrally extracted for DNA
      utilising the same protocol, and run through the same MPS platform (Illumina
      TruSeq Amplicon Cancer Panel). The sequencing artefacts in the 1-10% and the 10
      25% allele frequency ranges were assessed in 488 formalin-fixed tumours from the
      pilot phase of the Cancer 2015 cohort. All blocks were less than 2.5 years of age
      (mean 93 days). RESULTS: Consistent with the signature of DNA damage due to
      formalin fixation, many formalin-fixed samples displayed disproportionate levels
      of C>T/G>A changes in the 1-10% allele frequency range. Artefacts were less
      apparent in the 10-25% allele frequency range. Significantly, changes were
      inversely correlated with coverage indicating high levels of sequencing artefacts
      were associated with samples with low amounts of available amplifiable template
      due to fragmentation. The degree of fragmentation and sequencing artefacts
      differed between blocks sourced from different anatomical pathology laboratories.
      In a limited validation of potentially actionable low frequency mutations, a NRAS
      G12D mutation in a melanoma was shown to be a false positive. CONCLUSIONS: These
      findings indicate that DNA damage following formalin fixation remains a major
      challenge in laboratories working with MPS. Methodologies that assess, minimise
      or remove formalin-induced DNA damaged templates as part of MPS protocols will
      aid in the interpretation of genomic results leading to better patient outcomes.

PMID- 24885029
TI  - Efficacy of surface disinfectant cleaners against emerging highly resistant gram
      negative bacteria.
AB  - BACKGROUND: Worldwide, the emergence of multidrug-resistant gram-negative
      bacteria is a clinical problem. Surface disinfectant cleaners (SDCs) that are
      effective against these bacteria are needed for use in high risk areas around
      patients and on multi-touch surfaces. We determined the efficacy of several SDCs
      against clinically relevant bacterial species with and without common types of
      multidrug resistance. METHODS: Bacteria species used were ATCC strains; clinical
      isolates classified as antibiotic-susceptible; and multi-resistant clinical
      isolates from Klebsiella oxytoca, Klebsiella pneumoniae, and Serratia marcescens
      (all OXA-48 and KPC-2); Acinetobacter baumannii (OXA-23); Pseudomonas aeruginosa
      (VIM-1); and Achromobacter xylosoxidans (ATCC strain). Experiments were carried
      out according to EN 13727:2012 in quadruplicate under dirty conditions. The five
      evaluated SDCs were based on alcohol and an amphoteric substance (AAS), an oxygen
      releaser (OR), surface-active substances (SAS), or surface-active-substances plus
      aldehydes (SASA; two formulations). Bactericidal concentrations of SDCs were
      determined at two different contact times. Efficacy was defined as a log10 >= 5
      reduction in bacterial cell count. RESULTS: SDCs based on AAS, OR, and SAS were
      effective against all six species irrespective of the degree of multi-resistance.
      The SASA formulations were effective against the bacteria irrespective of degree
      of multi-resistance except for one of the four P. aeruginosa isolates (VIM-1). We
      found no general correlation between SDC efficacy and degree of antibiotic
      resistance. CONCLUSIONS: SDCs were generally effective against gram-negative
      bacteria with and without multidrug resistance. SDCs are therefore suitable for
      surface disinfection in the immediate proximity of patients. Single bacterial
      isolates, however, might have reduced susceptibility to selected biocidal agents.

PMID- 24885030
TI  - Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71
      elicited protective immunity in mice.
AB  - BACKGROUND: Human Enterovirus 71 (EV71) has emerged as the leading cause of viral
      encephalitis in children, especially in the Asia-Pacific regions. EV71 vaccine
      development is of high priority at present, and neutralization antibodies have
      been documented to play critical roles during in vitro and in vivo protection
      against EV71 infection. RESULTS: In this study, a novel strategy to produce EV71
      vaccine candidate based on recombinant multiple tandem linear neutralizing
      epitopes (mTLNE) was proposed. The three well identified EV71 linear neutralizing
      epitopes in capsid proteins, VP1-SP55, VP1-SP70 and VP2-SP28, were sequentially
      linked by a Gly-Ser linker ((G4S)3), and expressed in E.coli in fusion with the
      Trx and His tag at either terminal. The recombinant protein mTLNE was soluble and
      could be purified by standard affinity chromatography. Following three dosage of
      immunization in adult mice, EV71-specific IgG and neutralization antibodies were
      readily induced by recombinant mTLNE. IgG subtyping demonstrated that lgG1
      antibodies dominated the mTLNE-induced humoral immune response. Especially,
      cytokine profiling in spleen cells from the mTLNE-immunized mice revealed high
      production of IL-4 and IL-6. Finally, in vivo challenge experiments showed that
      passive transfer with anti-mTLNE sera conferred full protection against lethal
      EV71 challenge in neonatal mice. CONCLUSION: Our results demonstrated that this
      rational designed recombinant mTLNE might have the potential to be further
      developed as an EV71 vaccine in the future.

PMID- 24885031
TI  - Right axillary and femoral artery perfusion with mild hypothermia for aortic arch
      replacement.
AB  - OBJECTIVES: Aortic arch replacement is associated with increased mortality and
      morbidity especially in acute type-A aortic dissection. Although hypothermic
      circulatory arrest with selective antegrade cerebral perfusion has been widely
      used because of its excellent cerebral protection, its optimal perfusion
      characteristics are unknown. The present study investigates clinical results
      obtained after perfusion method modification and temperature management during
      cardiopulmonary bypass (CPB). METHODS: Between July 2010 and August 2012, 16
      consecutive adult patients (mean age 50.0 yr +/- 14.1 yr, range 25 yr to 73 yr,
      12 males, 4 females) who presented with acute Stanford type-A aortic dissection
      underwent aortic arch replacement (total arch, n = 11; hemiarch, n = 5) under
      mild hypothermia (31.1  degrees C +/- 1.5  degrees C) with right axillary and
      femoral artery perfusion. RESULTS: The mean CPB time was 201 min +/- 53 min, and
      the mean myocardial ischemic time was 140 min +/- 42 min. The mean selective
      cerebral perfusion time was 80 min +/- 16 min, and the mean lower-body
      circulatory arrest time was 20 min +/- 13 min. No patient death occurred within
      30 post-operative days. The following details were observed: new post-operative
      permanent neurologic deficit in 1 patient (6.3%), temporary neurologic deficit in
      2 patients (12.5%), acute renal dysfunction (creatinine level > 230 umol/L) in 3
      patients (18.8%) and mechanical ventilation > 72 h in 5 patients (31.2%).
      CONCLUSIONS: Aortic arch replacement for acute type-A aortic dissection under
      mild hypothermia with right axillary and femoral artery perfusion could be safely
      performed in the patient cohort.

PMID- 24885032
TI  - Six weeks of home enteral nutrition versus standard care after esophagectomy or
      total gastrectomy for cancer: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Each year approximately 3000 patients in the United Kingdom undergo
      surgery for esophagogastric cancer. Jejunostomy feeding tubes, placed at the time
      of surgery for early postoperative nutrition, have been shown to have a positive
      impact on clinical outcomes in the short term. Whether feeding out of hospital is
      of benefit is unknown. Local experience has identified that between 15 and 20% of
      patients required 'rescue' jejunostomy feeding for nutritional problems and
      weight loss while at home. This weight loss and poor nutrition may contribute to
      the detrimental effect on the overall quality of life (QoL) reported in these
      patients. METHODS/DESIGN: This randomized pilot and feasibility study will
      provide preliminary information on the routine use of jejunostomy feeding after
      hospital discharge in terms of clinical benefits and QoL. Sixty participants
      undergoing esophagectomy or total gastrectomy will be randomized to receive
      either a planned program of six weeks of home jejunostomy feeding after discharge
      from hospital (intervention) or treatment-as-usual (control). The intention of
      this study is to inform a multi-centre randomized controlled trial. The primary
      outcome measures will be recruitment and retention rates at six weeks and six
      months. Secondary outcome measures will include disease specific and general QoL
      measures, nutritional parameters, total and oral nutritional intake, hospital
      readmission rates, and estimates of healthcare costs. Up to 20 participants will
      also be enrolled in a qualitative sub-study that will explore participants' and
      carers' experiences of home tube feeding.The results will be disseminated by
      presentation at surgical, gastroenterological and dietetic meetings and
      publication in appropriate peer review journals. A patient-friendly lay summary
      will be made available on the University of Leicester and the University
      Hospitals of Leicester NHS Trust websites. The study has full ethical and
      institutional approval and started recruitment in July 2012. TRIAL REGISTRATION:
      UKClinical Research Network ID #12447 (Main study); UKCRN ID#13361 (Qualitative
      sub study); ClinicalTrials.gov #NCT01870817 (First registered 28 May 2013).

PMID- 24885033
TI  - Corticosteroid therapy in regressive autism: a retrospective study of effects on
      the Frequency Modulated Auditory Evoked Response (FMAER), language, and behavior.
AB  - BACKGROUND: Up to a third of children with Autism Spectrum Disorder (ASD)
      manifest regressive autism (R-ASD).They show normal early development followed by
      loss of language and social skills. Absent evidence-based therapies, anecdotal
      evidence suggests improvement following use of corticosteroids. This study
      examined the effects of corticosteroids for R-ASD children upon the 4 Hz
      frequency modulated evoked response (FMAER) arising from language cortex of the
      superior temporal gyrus (STG) and upon EEG background activity, language, and
      behavior. An untreated clinical convenience sample of ASD children served as
      control sample. METHODS: Twenty steroid-treated R-ASD (STAR) and 24 not-treated
      ASD patients (NSA), aged 3 - 5 years, were retrospectively identified from a
      large database. All study participants had two sequential FMAER and EEG
      studies;Landau-Kleffner syndrome diagnosis was excluded. All subjects' records
      contained clinical receptive and expressive language ratings based upon a priori
      developed metrics. The STAR group additionally was scored behaviorally regarding
      symptom severity as based on the Diagnostic and Statistical Manual IV (DSM-IV)
      ASD criteria list. EEGs were visually scored for abnormalities. FMAER responses
      were assessed quantitatively by spectral analysis. Treated and untreated group
      means and standard deviations for the FMAER, EEG, language, and behavior, were
      compared by paired t-test and Fisher's exact tests. RESULTS: The STAR group
      showed a significant increase in the 4 Hz FMAER spectral response and a
      significant reduction in response distortion compared to the NSA group. Star
      group subjects' language ratings were significantly improved and more STAR than
      NSA group subjects showed significant language improvement. Most STAR group
      children showed significant behavioral improvement after treatment. STAR group
      language and behavior improvement was retained one year after treatment. Groups
      did not differ in terms of minor EEG abnormalities. Steroid treatment produced no
      lasting morbidity. CONCLUSIONS: Steroid treatment was associated with a
      significantly increased FMAER response magnitude, reduction of FMAER response
      distortion, and improvement in language and behavior scores. This was not
      observed in the non-treated group. These pilot findings warrant a prospective
      randomized validation trial of steroid treatment for R-ASD utilizing FMAER, EEG,
      and standardized ASD, language and behavior measures, and a longer follow-up
      period.Please see related article http://www.biomedcentral.com/1741-7015/12/79.

PMID- 24885034
TI  - Intratumoral distribution of EGFR mutations and copy number in metastatic lung
      cancer, what impact on the initial molecular diagnosis?
AB  - BACKGROUND: Activating epidermal growth factor receptor (EGFR) mutations
      characterize a subgroup of non-small-cell lung cancer that benefit from first
      line EGFR tyrosine kinase inhibitors (EGFR-TKI). However, the existence of
      polyclonal cell populations may hinder personalized-medicine strategies as
      patients' screening often depends upon a single tumor-biopsy sample. The purpose
      of this study is to clarify and to validate in clinical testing conditions the
      accuracy of EGFR genotyping using different tumor sites and various types of
      samples (transthoracic, surgical or endoscopic biopsies and cytology specimens).
      METHODS: We conducted a retrospective review of 357 consecutive patients
      addressed for EGFR mutation screening in accordance with the directive of the
      European Medicines Agency (stage IV NSCLC). Fifty-seven samples were EGFR mutated
      and 40 had adequate tumor specimens for analysis on multiple spatially separated
      sites. Ten wild type samples were also analyzed. A total of 153 and 39 tumor
      fragments, from mutated and non-mutated cases respectively, were generated to
      analyze tumor heterogeneity or primary-metastatic discordances. After
      histological review of all fragments, EGFR genotyping was assessed using the
      routine diagnostic tools: fragment analysis for insertions and deletions and
      allele specific TaqMan probes for point mutations. EGFR copy number (CN) was
      evaluated by qPCR using TaqMan probes. RESULTS: The identification of EGFR
      mutations was independent of localization within primary tumor, of specimen type
      and consistent between primary and metastases. At the opposite, for half of the
      samples, tumor loci showed different EGFR copy number that may affect mutation
      detection cut-off. CONCLUSIONS: This is the largest series reporting multiple
      EGFR testing in Caucasians. It validates the accuracy of EGFR mutation screening
      from single tumor-biopsy samples before first line EGFR-TKI. The unpredictable
      variability in EGFR CN and therefore in EGFR wild type/mutant allelic ratio
      justifies the implementation of sensitive methods to identify patients with EGFR
      mutated tumors.

PMID- 24885035
TI  - Validation of administrative health data for the pediatric population: a scoping
      review.
AB  - BACKGROUND: The purpose of this research was to perform a scoping review of
      published literature on the validity of administrative health data for
      ascertaining health conditions in the pediatric population (<=20 years). METHODS:
      A comprehensive search of OVID Medline (1946 - present), CINAHL (1937 - present)
      and EMBASE (1947 - present) was conducted. Characteristics of validation studies
      that were abstracted included the study population, health condition, topic of
      the validation (e.g., single diagnosis code versus case-finding algorithm),
      administrative and validation data sources. Inter-rater agreement was measured
      using Cohen's kappa. Extracted data were analyzed using descriptive statistics.
      RESULTS: A total of 37 articles met the study inclusion criteria. Cohen's kappa
      for study inclusion/exclusion and data abstraction was 0.88 and 0.97,
      respectively. Most studies validated administrative data from the USA (43.2%) and
      Canada (24.3%), and focused on inpatient records (67.6%). Case-finding algorithms
      (56.7%) were more frequently validated than diagnoses codes alone (37.8%). Five
      conditions were validated in more than one study: diabetes mellitus, inflammatory
      bowel disease, asthma, rotavirus infection, and tuberculosis. CONCLUSIONS: This
      scoping review identified a number of gaps in the validation of administrative
      health data for pediatric populations, including limited investigation of
      outpatient populations and older pediatric age groups.

PMID- 24885037
TI  - A four-part working bibliography of neuroethics: part 1: overview and reviews-
      defining and describing the field and its practices.
AB  - BACKGROUND: Neuroethics entails investigations of neurocognitive mechanisms of
      morality and ethics; and studies and address of the ethical issues spawned by the
      use of neuroscience and its technologies to investigate cognition, emotion and
      actions. These two principal emphases, or what have been called "traditions" of
      neuroethics both mirror traditional bioethical discussions (such as debates about
      the safety of technological and pharmaceutical advances and ethical implications
      of new scientific and technological discoveries), and engage discourse about
      neuroscientific investigations of (proto-moral and moral) cognition, emotions and
      behaviors, and what such findings may mean for human beliefs and conduct - from
      the individual to the political levels.Given the growth, range, and rapid
      maturation of the field of neuroethics we provide an iterative, four-part
      document that affords a repository of international papers, books, and chapters
      that address the field in overview, and present discussion(s) of more particular
      aspects and topics of neuroethics. This first installment lists reviews and
      overviews of the discipline, and broad summaries of basic developments and issues
      of the field. METHODS: To systematically survey the neuroethics literature,
      searches were performed by accessing 11 databases, 8 additional literature
      depositories, and 4 individual journal searches using indexing language for
      National Library of Medicine (NLM) Medical Subject Heading databases. Searches
      and assurance against overlapping coverage were conducted using the RefWorks
      citation management program. RESULTS: Overview, review and reflections upon the
      history and multicultural perspectives of neuroethics were obtained and relevant
      listings from international journals, books, and book chapters are provided. Part
      I will be followed by three installments that will address a): the neuroscience
      of morality and ethics, including discussions of free will, and personal
      autonomy; b) "second tradition neuroethics", to include specific ethical issues
      in neuroscience; clinical neuroethics; and c) neuroethics education/training;
      neuroethics and society; neuroethics and law; neuroethics and policy; and
      international neuroethics.

PMID- 24885036
TI  - Lack of synergistic effect of resveratrol and sigma-1 receptor agonist (PRE-084)
      in SOD1G93A ALS mice: overlapping effects or limited therapeutic opportunity?
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an adult onset
      neurodegenerative disease characterized by the loss of motoneurons (MNs) in the
      spinal cord, brainstem and motor cortex, causing progressive paralysis and death.
      Nowadays, there is no effective therapy and most patients die 2-5 years after
      diagnosis. Sigma-1R is a transmembrane protein highly expressed in the CNS and
      specially enriched in MNs. Mutations on the Sigma-1R leading to frontotemporal
      lobar degeneration-ALS were recently described in human patients. We previously
      reported the therapeutic role of the selective sigma-1R agonist 2-(4-morpholi
      nethyl)1-phenylcyclohexanecarboxylate (PRE-084) in SOD1G93A ALS mice, that
      promoted spinal MN preservation and extended animal survival by controlling NMDA
      receptor calcium influx. Resveratrol (RSV, trans-3,4',5-trihydroxystilbene) is a
      natural polyphenol with promising neuroprotective effects. We recently found that
      RSV administration to SOD1G93A mice preserves spinal MN function and increases
      mice survival. These beneficial effects were associated to activation of Sirtuin
      1 (Sirt1) and AMP-activated protein kinase (AMPK) pathways, leading to the
      modulation of autophagy and an increase of mitochondrial biogenesis. The main
      goal of this work was to assess the effect of combined RSV and PRE-084
      administration in SOD1G93A ALS mice. METHODS: We determined the locomotor
      performance of the animals by rotarod test and evaluated spinal motoneuron
      function using electrophysiological tests. RESULTS: RSV plus PRE-084 treatment
      from 8 weeks of age significantly improved locomotor performance and spinal MN
      function, accompanied by a significant reduction of MN degeneration and an
      extension of mice lifespan. In agreement with our previous findings, there was an
      induction of PKC-specific phosphorylation of the NMDA-NR1 subunit and an
      increased expression and activation of Sirt1 and AMPK in the ventral spinal cord
      of treated SOD1G93A animals. CONCLUSIONS: Although combined PRE and RSV treatment
      significantly ameliorated SOD1G93A mice, it did not show a synergistic effect
      compared to RSV-only and PRE-084-only treated groups.

PMID- 24885038
TI  - Fetal asphyctic preconditioning alters the transcriptional response to perinatal
      asphyxia.
AB  - BACKGROUND: Genomic reprogramming is thought to be, at least in part, responsible
      for the protective effect of brain preconditioning. Unraveling mechanisms of this
      endogenous neuroprotection, activated by preconditioning, is an important step
      towards new clinical strategies for treating asphyctic neonates.Therefore, we
      investigated whole-genome transcriptional changes in the brain of rats which
      underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal
      asphyctic preconditioning (FAPA). Offspring were sacrificed 6 h and 96 h after
      birth, and whole-genome transcription was investigated using the Affymetrix
      Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma
      package. In addition to univariate analysis, we performed Gene Set Enrichment
      Analysis (GSEA) in order to derive results with maximum biological relevance.
      RESULTS: We observed minimal, 25% or less, overlap of differentially regulated
      transcripts across different experimental groups which leads us to conclude that
      the transcriptional phenotype of these groups is largely unique. In both the PA
      and FAPA group we observe an upregulation of transcripts involved in cellular
      stress. Contrastingly, transcripts with a function in the cell nucleus were
      mostly downregulated in PA animals, while we see considerable upregulation in the
      FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are
      exclusively regulated in FAPA animals. CONCLUSIONS: This study is the first to
      investigate whole-genome transcription in the neonatal brain after PA alone, and
      after perinatal asphyxia preceded by preconditioning (FAPA). We describe several
      genes/pathways, such as ubiquitination and proteolysis, which were not previously
      linked to preconditioning-induced neuroprotection. Furthermore, we observed that
      the majority of upregulated genes in preconditioned animals have a function in
      the cell nucleus, including several epigenetic players such as HDACs, which
      suggests that epigenetic mechanisms are likely to play a role in preconditioning
      induced neuroprotection.

PMID- 24885039
TI  - The validation of a questionnaire to assess barriers to enteral feeding in
      critically ill patients: a multicenter international survey.
AB  - BACKGROUND: A growing body of literature supports the need to identify and
      address barriers to knowledge use as a strategy to improve care delivery. To this
      end, we developed a questionnaire to assess barriers to enterally feeding
      critically ill adult patients, and sought to gain evidence to support the
      construct validity of this instrument by testing the hypothesis that barriers
      identified by the questionnaire are inversely associated with nutrition
      performance. METHODS: We conducted a multilevel multivariable regression analysis
      of data from an observational study in 55 Intensive Care Units (ICUs) from 5
      geographic regions. Data on nutrition practices were abstracted from 1153 patient
      charts, and 1439 critical care nurses completed the 'Barriers to Enterally
      Feeding critically Ill Patients' questionnaire. Our primary outcome was adequacy
      of calories from enteral nutrition (proportion of prescribed calories received
      enterally) and our primary predictor of interest was a barrier score derived from
      ratings of importance of items in the questionnaire. RESULTS: The mean adequacy
      of calories from enteral nutrition was 48 (Standard Deviation (SD)17)%.
      Evaluation for confounding identified patient type, proportion of nurse
      respondents working in the ICU greater than 5 years, and geographic region as
      important covariates. In a regression model adjusting for these covariates plus
      evaluable nutrition days and APACHE II score, we observed that a 10 point
      increase in overall barrier score is associated with a 3.5 (Standard Error
      (SE)1.3)% decrease in enteral nutrition adequacy (p-values <0.01). CONCLUSION:
      Our results provide evidence to support our a priori hypothesis that barriers
      negatively impact the provision of nutrition in ICUs, suggesting that our
      recently developed questionnaire may be a promising tool to identify these
      important factors, and guide the selection of interventions to optimize nutrition
      practice. Further research is required to illuminate if and how the type of
      barrier, profession of the provider, and geographic location of the hospital may
      influence this association.

PMID- 24885040
TI  - Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell
      carcinoma.
AB  - BACKGROUND: Receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is
      derived from uterine adenocarcinoma and can induce apoptosis in lymphocytes,
      allowing tumor cells to escape from immune surveillance. RCAS1 is reportedly
      expressed in a membranous pattern on tumor cell or soluble one in serum of
      patients. The aim of this study was to investigate expression patterns of RCAS1
      and the effect on apoptosis in oral squamous cell carcinoma (OSCC) cell lines.
      METHODS: In four kinds of OSCC cell lines (HSC-2, HSC-3, SQUU-A, and SQUU-B),
      RCAS1 mRNAs and proteins were determined by RT-PCR and immunocytochemistry.
      Membranous RCAS1 was determined by flow cytometry. Culture supernatants were
      analyzed for detection of soluble RCAS1 by dot blotting and enzyme-linked
      immunosorbent assay. Apoptotic ability of RCAS1 on the erythroid leukemia cell
      line K562 with the putative receptor was evaluated by flow cytometry in co
      culture with highly metastatic SQUU-B, with knocked-down RCAS1 cells or in a no
      cell contact condition. RESULTS: RCAS1 mRNA and proteins were expressed in all of
      OSCC cell lines. Membranous pattern were expressed in all cell lines, while
      soluble pattern was detected in all supernatants. RCAS1 mRNA, membranous and
      soluble RCAS1 were significantly seen in SQUU-B more than the other 3 cell lines
      (P < 0.05). K562 apoptosis was induced in co-culture with each of all cell lines,
      particularly with SQUU-B. Apoptosis was markedly reduced in co-culture with RCAS1
      knockdown cells, but was induced in co-culture without cell contract of SQUU-B.
      CONCLUSIONS: Our study suggests that RCAS1 has an apoptotic function via
      membranous/soluble expression pattern in OSCC cells. RCAS1 may thus affect tumor
      escape from immune surveillance in OSCC by inducing apoptosis.

PMID- 24885041
TI  - Protocol study: sexual and reproductive health knowledge, information-seeking
      behaviour and attitudes among Saudi women: a questionnaire survey of university
      students.
AB  - BACKGROUND: Sexual and reproductive health (SRH), a basic right for women
      worldwide, is infrequently researched in countries in the Middle East and North
      Africa (MENA). No empirical studies of SRH among Saudi women exist. This protocol
      describes a study to explore the SRH knowledge, information-seeking behaviour and
      attitudes of Saudi female university students. METHODS/DESIGN: This study will
      administer a questionnaire survey to female students at 13 universities in
      Riyadh, Saudi Arabia. The questionnaire was developed following a literature
      search to identify relevant content, with psychometrically tested tools used when
      available. The content layout and the wording and order of the questions were
      designed to minimize the risk of bias. The questionnaire has been translated into
      Arabic and piloted in preparation for administration to the study sample. Ethical
      approval for the study has been granted (reference no. QMREC2012/54). After
      questionnaire administration, the data will be collated, analysed and reported
      anonymously. The findings will be published in compliance with reporting
      guidelines for survey research. DISCUSSION: This study will be the first to
      provide fundamental information concerning Saudi females university students SRH
      knowledge and information needs.

PMID- 24885042
TI  - Deficiency of complement receptors CR2/CR1 in Cr2-/- mice reduces the extent of
      secondary brain damage after closed head injury.
AB  - Complement activation at the C3 convertase level has been associated with acute
      neuroinflammation and secondary brain injury after severe head trauma. The
      present study was designed to test the hypothesis that Cr2-/- mice, which lack
      the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation
      fragments, are protected from adverse sequelae of experimental closed head
      injury. Adult wild-type mice and Cr2-/- mice on a C57BL/6 genetic background were
      subjected to focal closed head injury using a standardized weight-drop device.
      Head-injured Cr2-/- mice showed significantly improved neurological outcomes for
      up to 72 hours after trauma and a significantly decreased post-injury mortality
      when compared to wild-type mice. In addition, the Cr2-/- genotype was associated
      with a decreased extent of neuronal cell death at seven days post-injury. Western
      blot analysis revealed that complement C3 levels were reduced in the injured
      brain hemispheres of Cr2-/- mice, whereas plasma C3 levels remained unchanged,
      compared to wild-type mice. Finally, head-injured Cr2-/- had an attenuated extent
      of post-injury C3 tissue deposition, decreased astrocytosis and microglial
      activation, and attenuated immunoglobulin M deposition in injured brains compared
      to wild-type mice. Targeting of these receptors for complement C3 fragments
      (CR2/CR1) may represent a promising future approach for therapeutic
      immunomodulation after traumatic brain injury.

PMID- 24885043
TI  - Incidence and risk factors for influenza-like-illness in the UK: online
      surveillance using Flusurvey.
AB  - BACKGROUND: Influenza and Influenza-like-illness (ILI) represents a substantial
      public health problem, but it is difficult to measure the overall burden as many
      cases do not access health care. Community cohorts have the advantage of not
      requiring individuals to present at hospitals and surgeries and therefore can
      potentially monitor a wider variety of cases. This study reports on the incidence
      and risk factors for ILI in the UK as measured using Flusurvey, an internet-based
      open community cohort. METHODS: Upon initial online registration participants
      were asked background characteristics, and every week were asked to complete a
      symptoms survey. We compared the representativeness of our sample to the overall
      population. We used two case definitions of ILI, which differed in whether
      fever/chills was essential. We calculated ILI incidence week by week throughout
      the season, and investigated risk factors associated with ever reporting ILI over
      the course of the season. Risk factor analysis was conducted using binomial
      regression. RESULTS: 5943 participants joined the survey, and 4532 completed the
      symptoms survey at least twice. Participants who filled in symptoms surveys at
      least twice filled in a median of nine symptoms surveys over the course of the
      study. 46.1% of participants reported at least one episode of ILI, and 6.0% of
      all reports were positive for ILI. Females had slightly higher incidence, and
      individuals over 65 had the lowest incidence. Incidence peaked just before
      Christmas and declined dramatically during school holidays. Multivariate
      regression showed that, for both definitions of ILI considered, being female,
      unvaccinated, having underlying health issues, having contact with children,
      being aged between 35 and 64, and being a smoker were associated with the highest
      risk of reporting an ILI. The use of public transport was not associated with an
      increased risk of ILI. CONCLUSIONS: Our results show that internet based
      surveillance can be used to measure ILI and understand risk factors. Vaccination
      is shown to be linked to a reduced risk of reporting ILI. Taking public transport
      does not increase the risk of reporting ILI. Flusurvey and other participatory
      surveillance techniques can be used to provide reliable information to policy
      makers in nearly real-time.

PMID- 24885044
TI  - Wheat in the Mediterranean revisited--tetraploid wheat landraces assessed with
      elite bread wheat Single Nucleotide Polymorphism markers.
AB  - BACKGROUND: Single Nucleotide Polymorphism (SNP) panels recently developed for
      the assessment of genetic diversity in wheat are primarily based on elite
      varieties, mostly those of bread wheat. The usefulness of such SNP panels for
      studying wheat evolution and domestication has not yet been fully explored and
      ascertainment bias issues can potentially affect their applicability when
      studying landraces and tetraploid ancestors of bread wheat. We here evaluate
      whether population structure and evolutionary history can be assessed in
      tetraploid landrace wheats using SNP markers previously developed for the
      analysis of elite cultivars of hexaploid wheat. RESULTS: We genotyped more than
      100 tetraploid wheat landraces and wild emmer wheat accessions, some of which had
      previously been screened with SSR markers, for an existing SNP panel and obtained
      publically available genotypes for the same SNPs for hexaploid wheat varieties
      and landraces. Results showed that quantification of genetic diversity can be
      affected by ascertainment bias but that the effects of ascertainment bias can at
      least partly be alleviated by merging SNPs to haplotypes. Analyses of population
      structure and genetic differentiation show strong subdivision between the
      tetraploid wheat subspecies, except for durum and rivet that are not separable. A
      more detailed population structure of durum landraces could be obtained than with
      SSR markers. The results also suggest an emmer, rather than durum, ancestry of
      bread wheat and with gene flow from wild emmer. CONCLUSIONS: SNP markers
      developed for elite cultivars show great potential for inferring population
      structure and can address evolutionary questions in landrace wheat. Issues of
      marker genome specificity and mapping need, however, to be addressed.
      Ascertainment bias does not seem to interfere with the ability of a SNP marker
      system developed for elite bread wheat accessions to detect population structure
      in other types of wheat.

PMID- 24885045
TI  - The use of different reference foods in determining the glycemic index of starchy
      and non-starchy test foods.
AB  - BACKGROUND: Glycemic index (GI) is intended to be a property of food but some
      reports are suggestive that GI is influenced by participant characteristics when
      glucose is used as a reference. OBJECTIVE: To examine the influence of different
      reference foods on observed GI. DESIGN: The GIs of five varieties of rice and a
      sugary beverage (LoGiCaneTM) were tested in 31 European and 32 Chinese
      participants using glucose or jasmine rice as reference foods. The GIs of two
      ready-to-eat breakfast cereals (Kellogg's cornflakes and Sustain) were tested in
      20 younger and 60 older people using glucose or Sustain as reference foods.
      RESULTS: The GIs of rice tended to be higher in the Chinese compared with the
      Europeans when glucose was used as a reference (jasmine 80 vs 68, P = 0.033;
      basmati 67 vs 57, P = 0.170; brown 78 vs 65, P = 0.054; Doongara 67 vs 55, P =
      0.045; parboiled 72 vs 57, P = 0.011). There were no between-group differences in
      GI when jasmine rice was the reference. The GIs of breakfast cereals tended to be
      lower in younger compared with older groups (cornflakes 64 vs 81, P = 0.008;
      Sustain 56 vs 66, P = 0.054). There was no between-group difference in the GI of
      cornflakes when Sustain was the reference (cornflakes 115 vs 120, P = 0.64).
      There was no ethnic difference in GI when glucose was the reference for another
      sugary food (LoGiCaneTM 60 vs 62; P = 0.69). CONCLUSIONS: A starchy reference may
      be more appropriate than a glucose beverage when attempting to derive universally
      applicable GI values of starchy foods. TRIAL REGISTRATION: The Chinese/European
      trial is registered with the Australian New Zealand Clinical Trials Registry as
      ACTRN12612000519853.

PMID- 24885046
TI  - Income related inequalities in New Cooperative Medical Scheme: a five-year
      empirical study of Junan County in China.
AB  - INTRODUCTION: The Chinese New Cooperative Medical Scheme (NCMS) was launched in
      2003 aiming at protecting the poor in rural areas from high health expenditures
      and improving access to health services. The income related inequality of the
      reform is a debating and concerning policy issue in China. The purpose of this
      study is to analyze the degree and changes of income related inequalities in both
      inpatient and outpatient services among NCMS enrollees from 2007 to 2011. DATA
      AND METHODS: Data was extracted from the NCMS information system of Junan County
      in Shandong province from 2007 to 2011. The study targeted all NCMS enrollees in
      the county, 726850 registered in 2011. Detailed information included demographic
      data, inpatient and outpatient data in each year. Descriptive analysis of
      quintiles and standardized concentration index (CI*) were employed to examine the
      income related inequalities in both inpatient and outpatient care. RESULTS: For
      inpatient care, the benefit rate CI* was positive (pro-rich) and increased from
      2007 to 2011 while for outpatient care was negative (pro-poor) and a decreasing
      pattern was observed. For outpatient visits and expenses, the CI* changed from a
      positive sign in 2007 to a negative sign in 2011 with some fluctuations. The pro
      rich inequality exacerbated for admissions while alleviated for length of stay
      and total inpatient expenses during the study period. The pro-rich inequality for
      inpatient reimbursement aggravated from 2007 to 2010 and alleviated from 2010 to
      2011. For outpatient reimbursement, it altered from a positive sign in 2007 to a
      small negative sign in 2011. Finally, the richer needed to afford more self
      payments for inpatient services and the CI* decreased from 2009 to 2011 while the
      inequality for outpatient self-payments changed from pro-rich in 2007 to pro-poor
      in 2011. CONCLUSIONS: In the NCMS, the pro-rich inequality dominated for the
      inpatient care while a pro-poor advantage was shown for outpatient care from 2007
      to 2011 in Junan. The extent of pro-rich inequality in length of stay, inpatient
      expenses and inpatient reimbursement increased from 2007 to 2009, but recently
      between 2010 and 2011 showed a change favoring the poor.

PMID- 24885047
TI  - Biosynthesis of trans-4-hydroxyproline by recombinant strains of Corynebacterium
      glutamicum and Escherichia coli.
AB  - BACKGROUND: Trans-4-hydroxy-L-proline (trans-Hyp), one of the hydroxyproline
      (Hyp) isomers, is a useful chiral building block in the production of many
      pharmaceuticals. Although there are some natural biosynthetic pathways of trans
      Hyp existing in microorganisms, the yield is still too low to be scaled up for
      industrial applications. Until now the production of trans-Hyp is mainly from the
      acid hydrolysis of collagen. Due to the increasing environmental concerns on
      those severe chemical processes and complicated downstream separation, it is
      essential to explore some environment-friendly processes such as constructing new
      recombinant strains to develop efficient process for trans-Hyp production.
      RESULT: In this study, the genes of trans-proline 4-hydroxylase (trans-P4H) from
      diverse resources were cloned and expressed in Corynebacterium glutamicum and
      Escherichia coli, respectively. The trans-Hyp production by these recombinant
      strains was investigated. The results showed that all the genes from different
      resources had been expressed actively. Both the recombinant C. glutamicum and E.
      coli strains could produce trans-Hyp in the absence of proline and 2
      oxoglutarate. CONCLUSIONS: The whole cell microbial systems for trans-Hyp
      production have been successfully constructed by introducing trans-P4H into C.
      glutamicum and E. coli. Although the highest yield was obtained in recombinant E.
      coli, using recombinant C. glutamicum strains to produce trans-Hyp was a new
      attempt.

PMID- 24885048
TI  - Modeling optimal cervical cancer prevention strategies in Nigeria.
AB  - BACKGROUND: This study aims to assess the most efficient combinations of
      vaccination and screening coverage for the prevention of cervical cancer (CC) at
      different levels of expenditure in Nigeria. METHODS: An optimization procedure,
      using a linear programming approach and requiring the use of two models (an
      evaluation and an optimization model), was developed. The evaluation model, a
      Markov model, estimated the annual number of CC cases at steady state in a
      population of 100,000 women for four alternative strategies: screening only;
      vaccination only; screening and vaccination; and no prevention. The results of
      the Markov model for each scenario were used as inputs to the optimization model
      determining the optimal proportion of the population to receive screening and/or
      vaccination under different scenarios. The scenarios varied by available budget,
      maximum screening and vaccination coverage, and overall reachable population.
      RESULTS: In the base-case optimization model analyses, with a coverage constraint
      of 20% for one lifetime screening, 95% for vaccination and a budget constraint of
      $1 per woman per year to minimize CC incidence, the optimal mix of prevention
      strategies would result in a reduction of CC incidence of 31% (3-dose vaccination
      available) or 46% (2-dose vaccination available) compared with CC incidence pre
      vaccination. With a 3-dose vaccination schedule, the optimal combination of the
      different strategies across the population would be 20% screening alone, 39%
      vaccination alone and 41% with no prevention, while with a 2-dose vaccination
      schedule the optimal combination would be 71% vaccination alone, and 29% with no
      prevention. Sensitivity analyses indicated that the results are sensitive to the
      constraints included in the optimization model as well as the cervical
      intraepithelial neoplasia (CIN) and CC treatment cost. CONCLUSIONS: The results
      of the optimization model indicate that, in Nigeria, the most efficient
      allocation of a limited budget would be to invest in both vaccination and
      screening with a 3-dose vaccination schedule, and in vaccination alone before
      implementing a screening program with a 2-dose vaccination schedule.

PMID- 24885049
TI  - A mixed-methods study on perceptions towards use of Rapid Ethical Assessment to
      improve informed consent processes for health research in a low-income setting.
AB  - BACKGROUND: Rapid Ethical Assessment (REA) is a form of rapid ethnographic
      assessment conducted at the beginning of research project to guide the consent
      process with the objective of reconciling universal ethical guidance with
      specific research contexts. The current study is conducted to assess the
      perceived relevance of introducing REA as a mainstream tool in Ethiopia. METHODS:
      Mixed methods research using a sequential explanatory approach was conducted from
      July to September 2012, including 241 cross-sectional, self-administered and 19
      qualitative, in-depth interviews among health researchers and regulators
      including ethics committee members in Ethiopian health research institutions and
      universities. RESULTS: In their evaluation of the consent process, only 40.2%
      thought that the consent process and information given were adequately understood
      by study participants; 84.6% claimed they were not satisfied with the current
      consent process and 85.5% thought the best interests of study participants were
      not adequately considered. Commonly mentioned consent-related problems included
      lack of clarity (48.1%), inadequate information (34%), language barriers (28.2%),
      cultural differences (27.4%), undue expectations (26.6%) and power imbalances
      (20.7%). About 95.4% believed that consent should be contextualized to the study
      setting and 39.4% thought REA would be an appropriate approach to improve the
      perceived problems. Qualitative findings helped to further explore the gaps
      identified in the quantitative findings and to map-out concerns related to the
      current research consent process in Ethiopia. Suggestions included, conducting
      REA during the pre-test (pilot) phase of studies when applicable. The need for
      clear guidance for researchers on issues such as when and how to apply the REA
      tools was stressed. CONCLUSION: The study findings clearly indicated that there
      are perceived to be correctable gaps in the consent process of medical research
      in Ethiopia. REA is considered relevant by researchers and stakeholders to
      address these gaps. Exploring further the feasibility and applicability of REA is
      recommended.

PMID- 24885050
TI  - Spheroid formation of human thyroid cancer cells under simulated microgravity: a
      possible role of CTGF and CAV1.
AB  - BACKGROUND: Multicellular tumor spheroids (MCTS) formed scaffold-free under
      microgravity are of high interest for research and medicine. Their formation
      mechanism can be studied in space in real microgravity or on Earth using ground
      based facilities (GBF), which simulate microgravity. On Earth, these experiments
      are more cost-efficient and easily performable. However, each GBF might exert
      device-specific and altered superimposingly gravity-dependent effects on the
      cells. RESULTS: FTC-133 human thyroid cancer cells were cultivated on a 2D
      clinostat (CN) and a random positioning machine (RPM) and compared with
      corresponding 1 g control cells. Harvested cell samples were investigated by
      microscopy, quantitative realtime-PCR and Multi-Analyte Profiling. Spheroid
      formation and growth occurred during 72 h of cultivation on both devices.
      Cytokine secretion and gene activation patterns frequently altered in different
      ways, when the cells were cultured either on the RPM or the CN. A decreased
      expression of CAV1 and CTGF in MCTS compared to adherent cells was observed after
      cultivation on both machines. CONCLUSION: The development of MCTS proceeds
      similarly on the RPM and the CN resembling the situation observed under real
      microgravity conditions, while no MCTS formation was observed at 1 g under
      identical experimental conditions. Simultaneously, changes in the regulation of
      CTGF and CAV1 appeared in a comparable manner on both machines. A relationship
      between these molecules and MCTS formation is discussed.

PMID- 24885051
TI  - Plasma NT pro-BNP, hs-CRP and big-ET levels at admission as prognostic markers of
      survival in hospitalized patients with dilated cardiomyopathy: a single-center
      cohort study.
AB  - BACKGROUND: Circulating N-terminal pro-B-type natriuretic peptide (NT pro-BNP),
      high- sensitivity C-reactive protein (hs-CRP) and big endothelin (big-ET) have
      been shown to be increased in heart failure and to contribute to both hemodynamic
      deterioration and cardiovascular remodeling. Here, we examined the prognostic
      value of the three neurohormones at admission in a population of hospitalized
      patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: This cohort
      study was undertaken in 622 hospitalized patients with DCM in Fuwai Hospital from
      January 2005 to September 2011 (female 26.5%, 51.4 +/- 14.6 years old). Standard
      demographics, echocardiography and routine blood samples were obtained shortly
      after admission. NT pro-BNP, hs-CRP and big-ET were measured, and their
      concentrations in relation to all-cause mortality were assessed through a mean
      follow-up of 2.6 +/- 1.6 years. Kaplan-Meier curves showed that the all-cause
      mortality rates were higher in patients with NT pro-BNP > 2247 pmol/L compared to
      patients with NT pro-BNP < 2247 pmol/L (11.9% vs 34.8%, log-rank chi2 = 35.588, P
      < 0.001), in patients with hs-CRP > 3.90 mg/L compared to patients with hs-CRP <
      3.90 mg/L (12.8% vs 33.6%, log-rank chi2 = 39.662, P < 0.001) and in patients
      with big-ET > 0.95 pmol/L compared to patients with big-ET <0.95 pmol/L (12.5% vs
      31.0%, log-rank chi2 = 17.890, P < 0.001). High circulating concentrations of NT
      pro-BNP (HR 2.217, 95% CI 1.015-4.846, P = 0.046) and hs-CRP (HR 1.922, 95% CI
      1.236-2.988, P = 0.004), but not big-ET, in addition to left atrial diameter and
      fasting blood glucose, were independent predictors of the outcome defined as all
      cause mortality. CONCLUSIONS: In a large population of patients with DCM, the
      circulating concentrations of NT pro-BNP and hs-CRP, but not big-ET, were
      independent markers of all-cause mortality.

PMID- 24885052
TI  - Clinical and epidemiological characteristics of adult hand, foot, and mouth
      disease in northern Zhejiang, China, May 2008-November 2013.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) is an infectious disease
      typically caused by enterovirus 71 (EV71) and Coxsackievirus A16. The incidence
      of HFMD appears to be increasing across the Asia Pacific region, with deaths
      occurring predominantly among children. Therefore, most HFMD reports focus on
      children and few have studied HFMD in adults. However, more adult HFMD cases may
      be seen in the foreseeable future as a result of global warming, continued viral
      evolution, and an increase in traveling. Thus, this study investigated the
      clinical and epidemiological characteristics of adult HFMD. METHODS: Case data of
      49 adult HFMD patients who attended The First Affiliated Hospital of Jiaxing
      College, China from May 2008 to November 2013 were obtained. Socio-demographic
      data were collected through follow-up phone calls. Throat swab specimens were
      tested for enterovirus by quantitative reverse transcription-polymerase chain
      reaction and further confirmed by virus isolation assay. For 10 patients infected
      with EV71, the gene encoding the EV71 VP1 protein was sequenced and analyzed.
      Data from 8,354 child HFMD patients and 49 adult patients in the fever clinic of
      The First Affiliated Hospital of Jiaxing College during the same period were
      collected for comparison. RESULTS: This study revealed that close contact with
      HFMD patients and poor personal hygiene consciousness were risk factors for adult
      HFMD. This study also found that EV71 subgenotype C4a was the most common
      pathogen associated with adult HFMD in this area. Furthermore, this study
      demonstrated several unique epidemiological characteristics of adult HFMD
      compared to child HFMD, such as the geographic and gender distribution of adult
      HFMD patients and HFMD seasonality. CONCLUSIONS: The findings in this study
      showed the potential threat of adult HFMD.

PMID- 24885053
TI  - The psychological impact of a dual-disaster caused by earthquakes and radioactive
      contamination in Ichinoseki after the Great East Japan Earthquake.
AB  - BACKGROUND: The psychological impact of dual-disasters (earthquakes and a nuclear
      accident), on affected communities is unknown. This study investigated the impact
      of a dual-disaster (earthquakes and radioactive contamination) on the prevalence
      of psychological distress in a landlocked city within the Tohoku area, Japan.
      METHODS: A cross-sectional mail-in survey with a random sample of inhabitants
      from Ichinoseki city was conducted eleven months after the disasters, and data
      from 902 respondents were analyzed by logistic regression models, with multiple
      imputation methodology. The K6 was used to determine psychological distress.
      RESULTS: The estimated prevalence of psychological distress was 48.0 percent.
      House damage due to earthquakes and anxiety about radioactive contamination were
      significantly associated with psychological distress (p < 0.05), while an
      interactive effect between house damage and anxiety about radioactive
      contamination was not significant. Being female, middle-to-low educational status
      and unemployed were additional risk factors for psychological distress.
      CONCLUSIONS: This dual-disaster was associated with a moderate prevalence of
      psychological distress in the area. The impact of the earthquake and radioactive
      contamination appeared additive.

PMID- 24885054
TI  - Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children.
AB  - BACKGROUND: Paneth cell metaplasia (PCM) is well described in adults but little
      is known about the distribution of colonic Paneth cells and the occurrence of PCM
      in a paediatric population. The aim of this study is to determine whether Paneth
      cell hyperplasia or metaplasia characteristically occurs in the colons of
      children with newly diagnosed idiopathic inflammatory bowel disease (IBD).
      METHODS: We retrospectively reviewed colonic series from 28 new diagnoses of
      paediatric IBD at a tertiary referral centre, and from a further 14 children with
      IBD-like symptoms whose colonic biopsies and ancillary investigations were
      normal. Paneth cells were counted at 6 anatomical sites in the colon, and at each
      site acute and chronic inflammation were assessed semi-quantitatively and the
      presence or absence of crypt architectural distortion and eosinophilia was
      documented. RESULTS: In control, ulcerative colitis (UC) and Crohn's disease (CD)
      groups there was a gradient of decreasing Paneth cell numbers from caecum to
      rectum. Paneth cells were not seen in the distal colon in the control group, but
      they were present there in 11 of 13 patients with ulcerative colitis and 14 of 15
      with Crohn's disease. Only patients with IBD showed Paneth cell hyperplasia,
      assessed as more than 10 Paneth cells per 10 well-oriented crypts at any site.
      There was a statistically significant increase in Paneth cells in the caecum,
      ascending, transverse and descending colon in UC and in the ascending,
      transverse, descending and sigmoid colon in CD compared with controls. There was
      no significant difference between UC and CD. There was no correlation between the
      site of PCM and acute or chronic inflammation, crypt distortion or eosinophilia.
      CONCLUSION: Paneth cells are found in the proximal but not the distal colon in
      otherwise normal paediatric colonic series. A high proportion of UC and CD
      patients show PCM in the distal colon. This is present early in the disease and
      does not correlate with histological features of chronicity.

PMID- 24885055
TI  - Unprecedented high insulin secretion in a healthy human subject after intravenous
      glucagon-like peptide-1: a case report.
AB  - BACKGROUND: The gut-derived incretin hormones, glucose-dependent insulinotropic
      polypeptide and glucagon-like peptide-1, are released in response to ingestion of
      nutrients. Both hormones are highly insulinotropic in strictly glucose-dependent
      fashions and glucagon-like peptide-1 is often referred to as one of the most
      insulinotropic substances known. CASE PRESENTATION: Plasma insulin and C-peptide
      concentrations were measured in a healthy Caucasian male (age: 53 years; body
      mass index: 28.6 kg/m2; fasting plasma glucose: 5.7 mM; 2 h plasma glucose value
      following 75 g-oral glucose tolerance test: 3.5 mM; glycated haemoglobin A1c:
      5.5%) during glucagon (1 mg) and meal (2,370 kJ) tests, and during two 2 h 15 mM
      hyperglycaemic clamps with continuous intravenous infusion of glucagon-like
      peptide-1 (1 pmol/kg/min) and glucose-dependent insulinotropic polypeptide (4
      pmol/kg/min), respectively. Normal insulin and C-peptide responses were observed
      during meal test (peak concentrations: 300 and 3,278 pM) and glucagon test (peak
      concentrations: 250 and 2,483 pM). During the hyperglycaemic clamp with
      continuous intravenous infusion of GLP-1 the subject exhibited plasma insulin and
      C-peptide concentrations of 13,770 and 22,380 pM, respectively. CONCLUSIONS: To
      our knowledge insulin and C-peptide concentrations of these magnitudes have never
      been reported. Thus, the present data support the view that glucagon-like peptide
      1 is one of the most insulinotropic substances known.

PMID- 24885056
TI  - Magnetic resonance imaging in the tibial epiphyseal growth plate development of
      Wistar rat.
AB  - OBJECTIVE: This research aims to investigate magnetic resonance imaging (MRI) in
      the tibial epiphyseal growth plate development of Wistar rat. METHODS: Fifty
      weanling Wistar rats were divided by a computerized blocking procedure into five
      groups. The rats received standard commercial feed with or without T-2 toxin
      additive, low-protein feed with or without T-2 toxin additive, and Kashin-Beck
      disease (KBD)-affected feed. RESULTS: Compared with the control group rat, MRI
      showed localized epiphyseal plate swelling, rough appearance, and uneven signal
      on the tibia of rats fed with KBD-affected feed. Histology confirmed the
      epiphyseal plate degeneration seen by MRI, and the degenerative changes were
      characterized by abnormal distribution of chondrocytes with loss and clustering,
      cartilage fragmentation, and erosion in group E. CONCLUSIONS: The MR image of the
      rat epiphyseal plate is altered in the KBD model rats, and epiphyseal plate MRI
      appearance has been reproduced by using T-2 toxin and KBD-affected feed of
      epidemic district.

PMID- 24885057
TI  - Tuberculosis patients' knowledge and beliefs about tuberculosis: a mixed methods
      study from the Pacific Island nation of Vanuatu.
AB  - BACKGROUND: The setting for this study was the Pacific island nation of Vanuatu,
      an archipelago of 82 islands, located in the South Pacific Ocean. Our objective
      was to assess the knowledge, attitudes and practices of tuberculosis (TB)
      patients towards TB. METHODS: This was a descriptive study using qualitative and
      quantitative methods. Quantitative analysis was based on the responses provided
      to closed questions, and we present frequencies to describe the TB patients'
      knowledge, attitudes and practice relating to TB. Qualitative analysis was based
      on open questions permitting fuller explanations. We used thematic analysis and
      developed a posteriori inductive categories to draw conclusions. RESULTS: Thirty
      five TB patients were interviewed; 22 (63%) were male. They attributed TB to
      cigarettes, kava, alcohol, contaminated food, sharing eating utensils and
      "kastom" (the local term for the traditional way of life, but also for sorcery).
      Most (94%) did not attribute TB to a bacterial cause. However, almost all TB
      patients (89%) thought that TB was best treated at a hospital with antibiotics.
      Three quarters (74%) experienced stigma after their TB diagnosis. Seeking health
      care from a traditional healer was common; 54% of TB patients stated that they
      would first consult a traditional healer for any illness. When seeking a
      diagnosis for signs and symptoms of TB, 34% first consulted a traditional healer.
      Patients cited cost, distance and beliefs about TB causation as reasons for first
      consulting a traditional healer or going to the hospital. Of the TB patients who
      consulted a traditional healer first, there was an average of two weeks delay
      before they consulted the health service. In some cases, however, the delay was
      up to six years. CONCLUSION: The majority of the TB patients interviewed did not
      attribute TB to a bacterial cause. Consulting a traditional healer for health
      care, including while seeking a diagnosis for TB symptoms, was common and may
      have delayed diagnosis. People require better information about TB to correct
      commonly held misperceptions about the disease. Traditional healers could also be
      engaged with the national TB programme, in order to refer people with signs and
      symptoms of TB to the nearest health service.

PMID- 24885058
TI  - Prevalence of unprotected anal intercourse in men who have sex with men recruited
      online versus offline: a meta-analysis.
AB  - BACKGROUND: Men who have sex with men (MSM) are a high risk population for human
      immunodeficiency virus (HIV) infection. Our study aims to find whether MSM who
      were recruited online had a higher prevalence of self-reported unprotected anal
      intercourse (UAI) than those who were recruited offline. METHODS: A meta-analysis
      was conducted from the results of published studies. The analysis was stratified
      by the participants' geographic location, the sample size and the date of the
      last reported UAI. RESULTS: Based on fourteen studies, MSM who were recruited
      online (online-based group) reported that 33.9% (5,961/17,580) of them had UAI
      versus 24.9% (2,700/10,853) of MSM who were recruited offline (offline-based
      group). The results showed that it is more likely for an online-based MSM group
      to have UAI with male partners than an offline-based MSM group [odds ratio (OR) =
      1.35, 95% CI = 1.13-1.62, P < 0.01]. The subgroup analysis results also showed
      that the prevalence of UAI was higher in the European subsample (OR = 1.38, 95%
      CI = 1.17-1.63, P < 0.01) and in sample sizes of more than 500 individuals (OR =
      1.32, 95% CI = 1.09-1.61, P < 0.01) in the online group compared to the offline
      group. The prevalence of UAI was also significantly higher when the time of the
      last UAI was during the last 3 or more months (OR = 1.40, 95% CI = 1.13-1.74, P <
      0.05) in the online group compared to the offline group. A sensitivity analysis
      was used to test the reliability of the results, and it reported that the results
      remained unchanged and had the same estimates after deleting any one of the
      included studies. CONCLUSIONS: A substantial percentage of MSM were recruited
      online, and they were more inclined to engage in UAI than MSM who were recruited
      offline. Targeted interventions of HIV prevention programs or services are
      recommended when designing preventive interventions to be delivered via the
      Internet.

PMID- 24885059
TI  - Synergistic effects of IL-4 and TNFalpha on the induction of B7-H1 in renal cell
      carcinoma cells inhibiting allogeneic T cell proliferation.
AB  - BACKGROUND: The importance of B7-H molecules for the T cell/tumor communication
      and its impact on renal cell carcinoma (RCC) progression and prognosis has been
      recently described. Cytokine treatment of RCC has earlier been shown to be
      beneficial in preclinical settings, but its clinical implementation has not
      proven to be as effective. This might be partially explained by the yet
      incomplete picture of cellular alterations in tumor cells upon cytokine treatment
      investigated in detail in this study. METHODS: RCC tumor cell lines were treated
      with different cytokines alone or in combination. The constitutive and/or
      cytokine-induced expression of cytokine receptors signaling components and B7-H
      molecules in RCC cells were analysed by qPCR and flow cytometry. A mcherry
      reporter gene construct containing B7-H1 promoter was cloned and its activity was
      determined upon transfection in cytokine-stimulated cells. Cytokine pretreated
      tumor cells were co-cultured with allogeneic CD8+ T cells from healthy donors and
      T cell proliferation as well as cytokine secretion was determined. RESULTS: A
      heterogeneous, but constitutive B7-H1,-H2,-H3 and H4 expression was found on
      human RCC cell lines. IL-4 and TNFalpha treatment led to strong synergistic
      induction of B7-H1 in RCC cells, whereas B7-H2 was only increased by TNFalpha. In
      contrast, B7-H3 and B7-H4 expression were not altered by these cytokines.
      Treatment of RCC cells with TNFalpha and IL-4 was accompanied by an activation of
      signaling molecules like NF-kappaB, IkappaB and STAT6. The cytokine-mediated up
      regulation of B7-H1 was due to transcriptional control as determined by an
      increased B7-H1 promoter activity in the presence of IL-4 and TNFalpha. Despite
      HLA class I and LFA-1 were also increased, the cytokine-mediated up-regulation of
      B7-H1 was more pronounced and caused an inhibition of allospecifc CD8+ T cell
      proliferation. CONCLUSION: Thus, IL-4 and TNFalpha, which could be released by
      immune cells of the tumor microenvironment, are able to control the B7-H1
      expression in RCC thereby altering T cell responses. These data are of importance
      for understanding the complex interplay of tumor cells with immune cells
      orchestrated by a number of different soluble and membrane bound mediators and
      for the implementation of check point antibodies directed against B7-H1.

PMID- 24885060
TI  - Suppression of aquaporin, a mediator of water channel control in the carcinogenic
      liver fluke, Opisthorchis viverrini.
AB  - BACKGROUND: Opisthorchiasis and Opisthorchis viverrini-associated bile duct
      cancer represent major public health threats in Thailand and Laos. The tegument
      of this food borne fluke plays pivotal roles in parasite metabolism, homeostasis
      and osmoregulation. Excretory/secretory products also pass from the fluke to the
      biliary environment, products that likely underlie pathogenesis of liver fluke
      infection. Aquaporins (AQPs), belong to the major intrinsic protein superfamily
      of integral plasma membrane channel proteins that selectively transport water
      across cell membranes. AQPs play key roles as water and ion transport channels
      through the tegument of helminth parasites. METHODS: Here, two forms of AQP mRNAs
      from the adult developmental stage of O. viverrini, termed O. viverrini aquaporin
      1 and -2 (Ov-aqp-1 and -2) were investigated. Roles of Ov-aqp-1 and -2 in the
      movement of water across the tegument of this carcinogenic liver fluke were
      investigated using RNA interference. RESULTS: Ov-AQP-1 and Ov-AQP-2 contain
      unique characteristic asparagine-proline-alanine (NPA) motifs of AQP
      transmembrane proteins. Phylogenetic analysis indicated that Ov-AQPs belong to an
      expanding group of aquaglyceroporin-like water channel proteins characterized
      from helminth and protozoan parasites, which is pivotal to the specialized
      requirements of water and solute control during parasitism. Elevated
      transcription of Ov-aqp-1 was evident in the egg, cercaria, metacercaria and
      adult stages of O. viverrini, whereas Ov-aqp-2 transcripts were detected at
      higher level in egg, metacercaria, cercaria and adult stage, respectively. RNA
      interference using electroporated dsRNA suppressed transcript levels of Ov-aqp-1
      and Ov-aqp-2 in adult worms by 58-99% over periods of up to 16 days in vitro.
      Suppression of Ov-aqp-1 and Ov-aqp-2 in vitro disabled water transport in adult
      flukes. CONCLUSION: The apparently pivotal roles of Ov-AQP in solute homeostasis
      at the fluke surface suggest that deeper investigation will be informative for
      the pathophysiology of O. viverrini, and may uncover intervention targets,
      particularly in view of the singularly notable predilection of this pathogen for
      residence within ducts of the biliary tree.

PMID- 24885061
TI  - Zoom in at African country level: potential climate induced changes in areas of
      suitability for survival of malaria vectors.
AB  - BACKGROUND: Predicting anopheles vectors' population densities and boundary
      shifts is crucial in preparing for malaria risks and unanticipated outbreaks.
      Although shifts in the distribution and boundaries of the major malaria vectors
      (Anopheles gambiae s.s. and An. arabiensis) across Africa have been predicted,
      quantified areas of absolute change in zone of suitability for their survival
      have not been defined. In this study, we have quantified areas of absolute change
      conducive for the establishment and survival of these vectors, per African
      country, under two climate change scenarios and based on our findings, highlight
      practical measures for effective malaria control in the face of changing climatic
      patterns. METHODS: We developed a model using CLIMEX simulation platform to
      estimate the potential geographical distribution and seasonal abundance of these
      malaria vectors in relation to climatic factors (temperature, rainfall and
      relative humidity). The model yielded an eco-climatic index (EI) describing the
      total favourable geographical locations for the species. The EI values were
      classified and exported to a GIS package. Using ArcGIS, the EI shape points were
      clipped to the extent of Africa and then converted to a raster layer using
      Inverse Distance Weighted (IDW) interpolation method. Generated maps were then
      transformed into polygon-based geo-referenced data set and their areas computed
      and expressed in square kilometers (km(2)). RESULTS: Five classes of EI were
      derived indicating the level of survivorship of these malaria vectors. The
      proportion of areas increasing or decreasing in level of survival of these
      malaria vectors will be more pronounced in eastern and southern African countries
      than those in western Africa. Angola, Ethiopia, Kenya, Mozambique, Tanzania,
      South Africa and Zambia appear most likely to be affected in terms of absolute
      change of malaria vectors suitability zones under the selected climate change
      scenarios. CONCLUSION: The potential shifts of these malaria vectors have
      implications for human exposure to malaria, as recrudescence of the disease is
      likely to be recorded in several new areas and regions. Therefore, the need to
      develop, compile and share malaria preventive measures, which can be adapted to
      different climatic scenarios, remains crucial.

PMID- 24885063
TI  - Home visits to improve breast health knowledge and screening practices in a less
      privileged area in Jordan.
AB  - BACKGROUND: Breast cancer is the most common cancer afflicting women in Jordan.
      This study aimed to assess the effects of an educational intervention through
      home visits, including offering free mammography screening vouchers, on changing
      women's breast health knowledge and screening practices for early detection of
      breast cancer in a less privileged area in Jordan. METHODS: Two thousand four
      hundred breast health awareness home visits were conducted and 2363 women aged 20
      79 years (median: 41) answered a pre-test interview-administrated questionnaire
      to assess their breast health knowledge and practices at the baseline. After a
      home-based educational session, 625 women aged 40 years or older were referred to
      free mammography screening. Five hundred and ninety six homes were revisited six
      months later and out of these 593 women participated in a post-test. The women's
      retained breast health knowledge, the changes in their reported breast health
      practices and their usage of the free mammography voucher, were assessed.
      RESULTS: The mean knowledge score increased significantly (p < 0.001) from 11.4
      in the pre-test to 15.7 in the post-test (maximum score: 16). At the six month
      follow-up the post-test showed significant (p < 0.001) improvement in women's
      perceived breast self-examination (BSE) knowledge, reported BSE practice and
      mammography screening. Out of 625 women that received a voucher for free
      mammography screening 73% attended the mammography unit, while only two women
      without a voucher went for mammography screening at the assigned unit. Women who
      received a follow-up visit were more likely to use the free mammography voucher
      compared to those who were not followed-up (83% vs. 67%; p < 0.001). CONCLUSIONS:
      Home visits by local community outreach workers that incorporated education about
      breast cancer and breast health in addition to offering free mammography
      screening vouchers were effective in improving women's breast health knowledge
      and practices in a less privileged area in Jordan.

PMID- 24885062
TI  - Analyses of clinicopathological, molecular, and prognostic associations of KRAS
      codon 61 and codon 146 mutations in colorectal cancer: cohort study and
      literature review.
AB  - BACKGROUND: KRAS mutations in codons 12 and 13 are established predictive
      biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest
      that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR
      therapy in colorectal cancer. However, clinicopathological, molecular, and
      prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation
      remain unclear. METHODS: We utilized a molecular pathological epidemiology
      database of 1267 colon and rectal cancers in the Nurse's Health Study and the
      Health Professionals Follow-up Study. We examined KRAS mutations in codons 12,
      13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological
      features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG
      island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite
      instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type
      cancers to avoid confounding by BRAF mutation. Cox proportional hazards models
      were used to compute mortality hazard ratio, adjusting for potential confounders,
      including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI.
      RESULTS: KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146
      mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal
      cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall,
      KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in
      KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P <
      0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These
      trends were evident irrespective of mutated codon, though statistical power was
      limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was
      significantly associated with clinical outcome or prognosis in univariate or
      multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) =
      0.81, 95% confidence interval (CI) = 0.29-2.26 for codon 61 mutation; colorectal
      cancer-specific mortality HR = 0.86, 95% CI = 0.42-1.78 for codon 146 mutation].
      CONCLUSIONS: Tumors with KRAS mutations in codons 61 and 146 account for an
      appreciable proportion (approximately 5%) of colorectal cancers, and their
      clinicopathological and molecular features appear generally similar to KRAS codon
      12 or 13 mutated cancers. To further assess clinical utility of KRAS codon 61 and
      146 testing, large-scale trials are warranted.

PMID- 24885064
TI  - Improvement of domain-level ortholog clustering by optimizing domain-specific sum
      of-pairs score.
AB  - BACKGROUND: Identification of ortholog groups is a crucial step in comparative
      analysis of multiple genomes. Although several computational methods have been
      developed to create ortholog groups, most of those methods do not evaluate
      orthology at the sub-gene level. In our method for domain-level ortholog
      clustering, DomClust, proteins are split into domains on the basis of alignment
      boundaries identified by all-against-all pairwise comparison, but it often fails
      to determine appropriate boundaries. RESULTS: We developed a method to improve
      domain-level ortholog classification using multiple alignment information. This
      method is based on a scoring scheme, the domain-specific sum-of-pairs (DSP)
      score, which evaluates ortholog clustering results at the domain level as the sum
      total of domain-level alignment scores. We developed a refinement pipeline to
      improve domain-level clustering, DomRefine, by optimizing the DSP score. We
      applied DomRefine to domain-level ortholog groups created by DomClust using a
      dataset obtained from the Microbial Genome Database for Comparative Analysis
      (MBGD), and evaluated the results using COG clusters and TIGRFAMs models as the
      reference data. Thus, we observed that the agreement between the resulting
      classification and the classifications in the reference databases is improved at
      almost every step in the refinement pipeline. Moreover, the refined
      classification showed better agreement than the classifications in the eggNOG
      databases when TIGRFAMs was used as the reference database. CONCLUSIONS:
      DomRefine is a useful tool for improving the quality of domain-level ortholog
      classification among microbial genomes. Combining with a rapid domain-level
      ortholog clustering method, such as DomClust, it can be used to create a high
      quality ortholog database that can serve as a solid basis for various comparative
      genome analyses.

PMID- 24885065
TI  - Usefulness of reinforcing interventions on continuous positive airway pressure
      compliance.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a high prevalence sleep disorder
      characterized by upper airway obstruction during sleep, nocturnal intermittent
      hypoxemia, poor sleep quality, risk for cardiovascular and metabolic diseases.
      The adherence to CPAP is the key for an effective management of these
      patients.The aim of the study was to assess the adherence to CPAP therapy with
      and without early reinforcing interventions, consisting of motivational
      reinforcement and technical support in the first month of therapy. METHODS: Forty
      patients with OSA undergoing counseling and a one year follow-up on a quarterly
      basis were included in the study. Twenty subjects (intervention group) underwent
      reinforcing interventions with telephone interviews in the first month of
      therapy, and twenty (control group) remained without reinforcing interventions.
      The two populations were homogeneous for age, severity of illness and BMI.
      RESULTS: During the first month, intervention group patients showed a higher
      number of nights with a device use >=4 hours. Average treatment adherence in the
      first month (days of therapy with at least 4 hours per night on the total number
      of days from device delivery) was 77.5% in the intervention group and 55.7% in
      the control group (p = 0.022). At one year the differences between the two groups
      were not significant. CONCLUSIONS: Our findings suggest that it is important that
      adequate time and effort is spent to ensure patient comfort at the time of CPAP
      therapy start to optimize acceptance and adherence to treatment, and suggest that
      it is necessary to maintain reinforcing interventions over time.

PMID- 24885066
TI  - Integrating complementary and alternative medicine into mainstream healthcare
      services: the perspectives of health service managers.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is increasingly included
      within mainstream integrative healthcare (IHC) services. Health service managers
      are key stakeholders central to ensuring effective integrative health care
      services. Yet, little research has specifically investigated the role or
      perspective of health service managers with regards to integrative health care
      services under their management. In response, this paper reports findings from an
      exploratory study focusing exclusively on the perspectives of health service
      managers of integrative health care services in Australia regarding the role of
      CAM within their service and the health service managers rational for
      incorporating CAM into clinical care. METHODS: Health service managers from seven
      services were recruited using purposive and snowball sampling. Semi-structured
      interviews were conducted with the health service managers. The services
      addressed trauma and chronic conditions and comprised: five community-based
      programs including drug and alcohol rehabilitation, refugee mental health and
      women's health; and two hospital-based specialist services. The CAM practices
      included in the services investigated included acupuncture, naturopathy, Western
      herbal medicine and massage. RESULTS: Findings reveal that the health service
      managers in this study understand CAM to enhance the holistic capacity of their
      service by: filling therapeutic gaps in existing healthcare practices; by
      treating the whole person; and by increasing healthcare choices. Health service
      managers also identified CAM as addressing therapeutic gaps through the provision
      of a mind-body approach in psychological trauma and in chronic disease management
      treatment. Health service managers describe the addition of CAM in their service
      as enabling patients who would otherwise not be able to afford CAM to gain access
      to these treatments thereby increasing healthcare choices. Some health service
      managers expressly align the notion of treating the whole person within a health
      promotion model and focus on the relevance of diet and lifestyle factors as
      central to a CAM approach. CONCLUSIONS: From the perspectives of the health
      service managers, these findings contribute to our understanding around the
      rationale to include CAM within mainstream health services that deal with
      psychological trauma and chronic disease. The broader implications of this study
      can help assist in the development of health service policy on CAM integration in
      mainstream healthcare services.

PMID- 24885067
TI  - Mitochondria--metabolism and beyond.

PMID- 24885068
TI  - The CONSENSUS study: protocol for a mixed methods study to establish which
      outcomes should be included in a core outcome set for oropharyngeal cancer.
AB  - BACKGROUND: The incidence of oropharyngeal cancer is increasing in the developed
      world. This has led to a large rise in research activity and clinical trials in
      this area, yet there is no consensus on which outcomes should be measured. As a
      result, the outcomes measured often differ between trials of comparable
      interventions, making the combination or comparison of results between trials
      impossible. Outcomes may also be 'cherry-picked', such that favourable results
      are reported, and less favourable results withheld. The development of a minimum
      outcome reporting standard, known as a core outcome set, goes some way to
      addressing these problems. Core outcome sets are ideally developed using a
      patient-centred approach so that the outcomes measured are relevant to patients
      and clinical practice. Core outcome sets drive up the quality and relevance of
      research by ensuring that the right outcomes are consistently measured and
      reported in trials in specific areas of health or healthcare. METHODS/DESIGN:
      This is a mixed methods study involving three phases to develop a core outcome
      set for oropharyngeal cancer clinical trials. Firstly, a systematic review will
      establish which outcomes are measured in published oropharyngeal cancer
      randomised controlled trials (RCTs). Secondly, qualitative interviews with
      patients and carers in the UK and the USA will aim to establish which outcomes
      are important to these stakeholders. Data from these first two stages will be
      used to develop a comprehensive list of outcomes to be considered for inclusion
      in the core outcome set. In the third stage, patients and clinicians will
      participate in an iterative consensus exercise known as a Delphi study to refine
      the contents of the core outcome set. This protocol lays out the methodology to
      be implemented in the CONSENSUS study. DISCUSSION: A core outcome set defines a
      minimum outcome reporting standard for clinical trials in a particular area of
      health or healthcare. Its consistent implementation in oropharyngeal cancer
      clinical trials will improve the quality and relevance of research. TRIALS AND
      REGISTRATION: This study is registered at the National Institute for Health
      Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January
      2013).

PMID- 24885070
TI  - One-stage dorsal inlay oral mucosa graft urethroplasty for anterior urethral
      stricture.
AB  - BACKGROUND: Anterior urethral stricture remains a great challenge. We reported
      our clinical technique and results by using inlay dorsal buccal mucosal graft
      urethroplasty for repair of anterior urethral stricture. METHODS: From January
      2005 to July 2008, 87 male patients (range from 9 to 72 years old) with anterior
      urethral stricture have been treated by one-stage dorsal inlay oral mucosal graft
      (OMG) urethroplasty. All patients gave written informed consent for their
      participation. All patients showed that urethral plate had been either scarred or
      removed previously. In our surgery, the urethra was dissected dorsally and scar
      of the urethral plate was removed. The remnant urethral plate was split at
      midline and a buccal mucosa patch was inserted between the two parts. Neourethra
      was tubularized and covered with dartos flap. The pre-operative assessments
      included clinical data, urine analysis, uroflowmetry, retrograde and voiding
      cystogram, urethral ultrasonography and endoscopy. Postoperatively, the flow rate
      and void residual volume were analyzed by uroflowmetry and sonography. Any
      further instrumentation to assist voiding was considered as failure. RESULTS:
      After 12 to 48 months (mean: 25.8 months), 78 patients (89.66%) have shown good
      results by the one-stage urethroplasty. However, 9 patients (10.3%) required
      further treatment due to recurrence, while 6 patients (6.9%) had fistula.
      CONCLUSIONS: This one-stage dorsal inlay approach using dorsal oral mucosal
      grafts is a reliable method to create a substitute urethral plate for
      tubularization. This approach represents a safe option for anterior urethral
      stricture patients especially with grossly scarred urethral plate.

PMID- 24885069
TI  - Translating evidence-based interventions for implementation: Experiences from
      Project HEAL in African American churches.
AB  - BACKGROUND: Community-based approaches have been increasing in the effort to
      raise awareness and early detection for cancer and other chronic disease.
      However, many times, such interventions are tested in randomized trials, become
      evidence-based, and then fail to reach further use in the community. Project HEAL
      (Health through Early Awareness and Learning) is an implementation trial that
      aims to compare two strategies of implementing evidence-based cancer
      communication interventions in African American faith-based organizations.
      METHOD: This article describes the community-engaged process of transforming
      three evidence-based cancer communication interventions into a coherent, branded
      strategy for training community health advisors with two delivery mechanisms.
      Peer community health advisors receive training through either a traditional
      classroom approach (with high technical assistance/support) or a web-based
      training portal (with low technical assistance/support). RESULTS: We describe the
      process, outline the intervention components, report on the pilot test, and
      conclude with lessons learned from each of these phases. Though the pilot phase
      showed feasibility, it resulted in modifications to data collection protocols and
      team and community member roles and expectations. CONCLUSIONS: Project HEAL
      offers a promising strategy to implement evidence-based interventions in
      community settings through the use of technology. There could be wider
      implications for chronic disease prevention and control.

PMID- 24885071
TI  - Anterior segment dysgenesis associated with Williams-Beuren syndrome: a case
      report and review of the literature.
AB  - BACKGROUND: Williams-Beuren syndrome is characterized by mild mental retardation,
      specific neurocognitive profile, hypercalcemia during infancy, distinctive facial
      features and cardiovascular diseases. We report on complete ophthalmologic,
      sonographic and genetic evaluation of a girl with a clinical phenotype of
      Williams-Beuren syndrome, associated with unilateral anterior segment dysgenesis
      and bilateral cleft of the soft and hard palate. These phenotypic features have
      not been linked to the haploinsufficiency of genes involved in the microdeletion.
      CASE PRESENTATION: A term born girl presented at the initial examination with
      clouding of the right cornea. On ultrasound biomicroscopy the anterior chamber
      structures were difficult to differentiate, showing severe adhesions from the
      opacified cornea to the iris with a kerato-irido-lenticular contact to the
      remnant lens, a finding consistent with Peters' anomaly. Genetic analyses
      including FISH confirmed a loss of the critical region 7q11.23, usually
      associated with the typical Williams-Beuren syndrome. Microsatellite analysis
      showed a loss of about 2.36 Mb. CONCLUSIONS: A diagnosis of Williams-Beuren
      syndrome was made based on the microdeletion of 7q11.23. The unique features,
      including unilateral microphthalmia and anterior segment dysgenesis, were
      unlikely to be caused by the microdeletion. Arguments in favor of the latter are
      unilateral manifestation, as well as the fact that numerous patients with
      deletions of comparable or microscopically visible size have not shown similar
      manifestations.

PMID- 24885072
TI  - Bloodstream infections and sepsis in Greece: over-time change of epidemiology and
      impact of de-escalation on final outcome.
AB  - BACKGROUND: Choice of empirically prescribed antimicrobials for sepsis management
      depends on epidemiological factors. The epidemiology of sepsis in Greece was
      studied in two large-periods. METHODS: Sepsis due to bloodstream infections (BSI)
      from July 2006 until March 2013 was recorded in a multicenter study in 46
      departments. Patients were divided into sepsis admitted in the emergencies and
      hospitalized in the general ward (GW) and sepsis developing after admission in
      the Intensive Care Unit (ICU). The primary endpoints were the changes of
      epidemiology and the factors related with BSIs by multidrug-resistant (MDR)
      pathogens; the secondary endpoint was the impact of de-escalation on
      antimicrobial therapy. RESULTS: 754 patients were studied; 378 from 2006-2009 and
      376 from 2010-2013. Major differences were recorded between periods in the GW.
      They involved increase of: sepsis severity; the incidence of underlying diseases;
      the incidence of polymicrobial infections; the emergence of Klebsiella pneumoniae
      as a pathogen; and mortality. Factors independently related with BSI by MDR
      pathogens were chronic hemofiltration, intake of antibiotics the last three
      months and residence into long-term care facilities. De-escalation in BSIs by
      fully susceptible Gram-negatives did not affect final outcome. Similar
      epidemiological differences were not found in the ICU; MDR Gram-negatives
      predominated in both periods. CONCLUSIONS: The epidemiology of sepsis in Greece
      differs in the GW and in the ICU. De-escalation in the GW is a safe strategy.

PMID- 24885073
TI  - Trait impulsivity and impaired prefrontal impulse inhibition function in
      adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.
AB  - BACKGROUND: Recent studies suggest that Internet gaming addiction (IGA) is an
      impulse disorder, or is at least related to impulse control disorders. In the
      present study, we hypothesized that different facets of trait impulsivity may be
      specifically linked to the brain regions with impaired impulse inhibition
      function in IGA adolescents. METHODS: Seventeen adolescents with IGA and
      seventeen healthy controls were scanned during performance of a response
      inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness
      Scale (BIS)-11 was used to assess impulsivity. RESULTS: There were no differences
      in the behavioral performance on the Go/No-Go task between the groups. However,
      the IGA group was significantly hyperactive during No-Go trials in the left
      superior medial frontal gyrus, right anterior cingulate cortex, right
      superior/middle frontal gyrus, left inferior parietal lobule, left precentral
      gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal
      gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were
      significantly hypoactive during No-Go trials. Activation of the left superior
      medial frontal gyrus was positively associated with BIS-11 and Chen Internet
      Addiction Scale (CIAS) total score across IGA participants. CONCLUSIONS: Our data
      suggest that the prefrontal cortex may be involved in the circuit modulating
      impulsivity, while its impaired function may relate to high impulsivity in
      adolescents with IGA, which may contribute directly to the Internet addiction
      process.

PMID- 24885074
TI  - Singlet oxygen generation on porous superhydrophobic surfaces: effect of gas flow
      and sensitizer wetting on trapping efficiency.
AB  - We describe physical-organic studies of singlet oxygen generation and transport
      into an aqueous solution supported on superhydrophobic surfaces on which silicon
      phthalocyanine (Pc) particles are immobilized. Singlet oxygen ((1)O2) was trapped
      by a water-soluble anthracene compound and monitored in situ using a UV-vis
      spectrometer. When oxygen flows through the porous superhydrophobic surface,
      singlet oxygen generated in the plastron (i.e., the gas layer beneath the liquid)
      is transported into the solution within gas bubbles, thereby increasing the
      liquid-gas surface area over which singlet oxygen can be trapped. Higher
      photooxidation rates were achieved in flowing oxygen, as compared to when the gas
      in the plastron was static. Superhydrophobic surfaces were also synthesized so
      that the Pc particles were located in contact with, or isolated from, the aqueous
      solution to evaluate the relative effectiveness of singlet oxygen generated in
      solution and the gas phase, respectively; singlet oxygen generated on particles
      wetted by the solution was trapped more efficiently than singlet oxygen generated
      in the plastron, even in the presence of flowing oxygen gas. A mechanism is
      proposed that explains how Pc particle wetting, plastron gas composition and flow
      rate as well as gas saturation of the aqueous solution affect singlet oxygen
      trapping efficiency. These stable superhydrophobic surfaces, which can physically
      isolate the photosensitizer particles from the solution may be of practical
      importance for delivering singlet oxygen for water purification and medical
      devices. 

PMID- 24885075
TI  - Complete steady-state rate equation for DNA ligase and its use for measuring
      product kinetic parameters of NAD+-dependent DNA ligase from Haemophilus
      influenzae.
AB  - BACKGROUND: DNA ligase seals the nicks in the phosphodiester backbone between
      Okazaki fragments during DNA replication. DNA ligase has an unusual Bi Ter Ping
      Pong kinetic mechanism. Its substrates in eubacteria are NAD+ and nicked DNA
      (nDNA). Its products are nicotinamide mononucleotide (NMN), adenosine 5'
      monophosphate (AMP), and sealed DNA. Investigation of the kinetic mechanism and
      measurement of the kinetic constants of DNA ligase using steady-state kinetics
      would benefit from the availability of the complete steady-state rate equation,
      including terms for product concentrations and product-related kinetic constants,
      which has not previously been published. RESULTS: The rate equations for two
      possible Bi Ter kinetic mechanisms for DNA ligase, including products, are
      reported. The mechanisms differ according to whether the last two products, AMP
      and sealed DNA, are released in an ordered or rapid-equilibrium random (RER)
      manner. Steady-state kinetic studies of product inhibition by NMN and AMP were
      performed with Haemophilus influenzae NAD+-dependent DNA ligase. The complete
      rate equation enabled measurement of dissociation constants for NAD+, NMN, and
      AMP and eliminated one of 3 possible product release mechanisms. CONCLUSIONS:
      Steady-state kinetic product inhibition experiments and complete steady-state
      kinetic rate equations were used to measure dissociation constants of NAD+, NMN,
      and AMP and eliminate the possibility that AMP is the second product released in
      an ordered mechanism. Determining by steady-state kinetics whether the release of
      sealed DNA and AMP products goes by an ordered (AMP last off) or RER mechanism
      was shown to require a product inhibition study using sealed DNA.

PMID- 24885076
TI  - Retraining and assessing hand movement after stroke using the MusicGlove:
      comparison with conventional hand therapy and isometric grip training.
AB  - BACKGROUND: It is thought that therapy should be functional, be highly
      repetitive, and promote afferent input to best stimulate hand motor recovery
      after stroke, yet patients struggle to access such therapy. We developed the
      MusicGlove, an instrumented glove that requires the user to practice gripping
      like movements and thumb-finger opposition to play a highly engaging, music
      based, video game. The purpose of this study was to 1) compare the effect of
      training with MusicGlove to conventional hand therapy 2) determine if MusicGlove
      training was more effective than a matched form of isometric hand movement
      training; and 3) determine if MusicGlove game scores predict clinical outcomes.
      METHODS: 12 chronic stroke survivors with moderate hemiparesis were randomly
      assigned to receive MusicGlove, isometric, and conventional hand therapy in a
      within-subjects design. Each subject participated in six one-hour treatment
      sessions three times per week for two weeks, for each training type, for a total
      of 18 treatment sessions. A blinded rater assessed hand impairment before and
      after each training type and at one-month follow-up including the Box and Blocks
      (B & B) test as the primary outcome measure. Subjects also completed the
      Intrinsic Motivation Inventory (IMI). RESULTS: Subjects improved hand function
      related to grasping small objects more after MusicGlove compared to conventional
      training, as measured by the B & B score (improvement of 3.21+/-3.82 vs. -0.29+/
      2.27 blocks; P=0.010) and the 9 Hole Peg test (improvement of 2.14+/-2.98 vs. 
      0.85+/-1.29 pegs/minute; P=0.005). There was no significant difference between
      training types in the broader assessment batteries of hand function. Subjects
      benefited less from isometric therapy than MusicGlove training, but the
      difference was not significant (P>0.09). Subjects sustained improvements in hand
      function at a one month follow-up, and found the MusicGlove more motivating than
      the other two therapies, as measured by the IMI. MusicGlove games scores
      correlated strongly with the B & B score. CONCLUSIONS: These results support the
      hypothesis that hand therapy that is engaging, incorporates high numbers of
      repetitions of gripping and thumb-finger opposition movements, and promotes
      afferent input is a promising approach to improving an individual's ability to
      manipulate small objects. The MusicGlove provides a simple way to access such
      therapy.

PMID- 24885077
TI  - Comparative genomic analysis of the R2R3 MYB secondary cell wall regulators of
      Arabidopsis, poplar, rice, maize, and switchgrass.
AB  - BACKGROUND: R2R3 MYB proteins constitute one of the largest plant transcription
      factor clades and regulate diverse plant-specific processes. Several R2R3 MYB
      proteins act as regulators of secondary cell wall (SCW) biosynthesis in
      Arabidopsis thaliana (At), a dicotyledenous plant. Relatively few studies have
      examined SCW R2R3 MYB function in grasses, which may have diverged from dicots in
      terms of SCW regulatory mechanisms, as they have in cell wall composition and
      patterning. Understanding cell wall regulation is especially important for
      improving lignocellulosic bioenergy crops, such as switchgrass. RESULTS: Here, we
      describe the results of applying phylogenic, OrthoMCL, and sequence identity
      analyses to classify the R2R3 MYB family proteins from the annotated proteomes of
      Arabidposis, poplar, rice, maize and the initial genome (v0.0) and translated
      transcriptome of switchgrass (Panicum virgatum). We find that the R2R3 MYB
      proteins of the five species fall into 48 subgroups, including three dicot
      specific, six grass-specific, and two panicoid grass-expanded subgroups. We
      observe four classes of phylogenetic relationships within the subgroups of known
      SCW-regulating MYB proteins between Arabidopsis and rice, ranging from likely one
      to-one orthology (for AtMYB26, AtMYB103, AtMYB69) to no homologs identifiable
      (for AtMYB75). Microarray data for putative switchgrass SCW MYBs indicate that
      many maintain similar expression patterns with the Arabidopsis SCW regulators.
      However, some of the switchgrass-expanded candidate SCW MYBs exhibit differences
      in gene expression patterns among paralogs, consistent with subfunctionalization.
      Furthermore, some switchgrass representatives of grass-expanded clades have gene
      expression patterns consistent with regulating SCW development. CONCLUSIONS: Our
      analysis suggests that no single comparative genomics tool is able to provide a
      complete picture of the R2R3 MYB protein family without leaving ambiguities, and
      establishing likely false-negative and -positive relationships, but that used
      together a relatively clear view emerges. Generally, we find that most R2R3 MYBs
      that regulate SCW in Arabidopsis are likely conserved in the grasses. This
      comparative analysis of the R2R3 MYB family will facilitate transfer of
      understanding of regulatory mechanisms among species and enable control of SCW
      biosynthesis in switchgrass toward improving its biomass quality.

PMID- 24885078
TI  - Unfiltered Administration of the YMRS and CDRS-R in a Clinical Sample of
      Children.
AB  - The objective of this study is to evaluate discriminative validity of the Young
      Mania Rating Scale (YMRS) and Children's Depression Rating Scale-Revised (CDRS-R)
      in a clinical sample of children when administered in an unfiltered manner (i.e.,
      regardless of whether symptoms occur in a mood episode). The Kiddie Schedule for
      Affective Disorders and Schizophrenia is the gold standard for assessing
      psychiatric disorders in children and was used to make diagnoses in this study.
      Using a sample of 707 treatment-seeking youth (ages 6-12 years, Mage = 9.7 years,
      67.6% male), receiver operating curve analyses were performed and diagnostic
      likelihood ratios (DLRs) were calculated to evaluate the ability to change the
      odds and differentiate bipolar disorder from other disorders (using the YMRS) and
      depression from other disorders (using the CDRS-R). Using unfiltered
      administration, the YMRS achieved good discriminative validity when classifying
      bipolar disorder compared to other disorders (Area Under the Curve [AUC] = .86)
      and increased odds of a bipolar diagnosis given a score in the highest quintile
      (DLR = 6.12). Using unfiltered administration, the CDRS-R achieved moderate to
      good discriminative validity in classifying depressive disorders (DD) compared to
      other disorders (AUCBD in comparison = .78; AUCBD not in comparison = .84) and
      slightly increased odds of DD given a score in the highest quintile (DLRBD in
      comparison = 3.12; DLRBD not in comparison = 5.08). The YMRS and CDRS-R have
      moderate to good discriminative validity when administered in an unfiltered way
      in a sample of treatment seeking youth. 

PMID- 24885079
TI  - fPoxDB: fungal peroxidase database for comparative genomics.
AB  - BACKGROUND: Peroxidases are a group of oxidoreductases which mediate electron
      transfer from hydrogen peroxide (H2O2) and organic peroxide to various electron
      acceptors. They possess a broad spectrum of impact on industry and fungal
      biology. There are numerous industrial applications using peroxidases, such as to
      catalyse highly reactive pollutants and to breakdown lignin for recycling of
      carbon sources. Moreover, genes encoding peroxidases play important roles in
      fungal pathogenicity in both humans and plants. For better understanding of
      fungal peroxidases at the genome-level, a novel genomics platform is required. To
      this end, Fungal Peroxidase Database (fPoxDB;
      http://peroxidase.riceblast.snu.ac.kr/) has been developed to provide such a
      genomics platform for this important gene family. DESCRIPTION: In order to
      identify and classify fungal peroxidases, 24 sequence profiles were built and
      applied on 331 genomes including 216 from fungi and Oomycetes. In addition, NoxR,
      which is known to regulate NADPH oxidases (NoxA and NoxB) in fungi, was also
      added to the pipeline. Collectively, 6,113 genes were predicted to encode 25 gene
      families, presenting well-separated distribution along the taxonomy. For
      instance, the genes encoding lignin peroxidase, manganese peroxidase, and
      versatile peroxidase were concentrated in the rot-causing basidiomycetes,
      reflecting their ligninolytic capability. As a genomics platform, fPoxDB provides
      diverse analysis resources, such as gene family predictions based on fungal
      sequence profiles, pre-computed results of eight bioinformatics programs,
      similarity search tools, a multiple sequence alignment tool, domain analysis
      functions, and taxonomic distribution summary, some of which are not available in
      the previously developed peroxidase resource. In addition, fPoxDB is
      interconnected with other family web systems, providing extended analysis
      opportunities. CONCLUSIONS: fPoxDB is a fungi-oriented genomics platform for
      peroxidases. The sequence-based prediction and diverse analysis toolkits with
      easy-to-follow web interface offer a useful workbench to study comparative and
      evolutionary genomics of peroxidases in fungi.

PMID- 24885080
TI  - Prevalence and correlates of leisure-time physical activity among Nigerians.
AB  - BACKGROUND: Physical inactivity levels are rising in many countries with major
      implications for the prevalence of non-communicable diseases and the general
      health of the population worldwide. We conducted this study to examine leisure
      time physical activity levels among African adults in an urban setting. METHODS:
      We conducted a cross-sectional study among a random sample of 1,058 adults at a
      government worksite, in Abuja, an urban Nigerian city. We used log-binomial
      regression models to estimate the multivariable-adjusted associations of
      correlates of physical activity. RESULTS: The mean age of the study population
      was 42 +/- 9.3 years, 60% were men and 40% were women. The mean metabolic
      equivalent hours per week for all the participants was 6.8 +/- 7.2. In univariate
      analysis comparing the lowest to highest tertiles of physical activity, the
      prevalence ratio (PR) and (95% confidence interval, CI) was 0.95 (0.81-1.11) p =
      0.49, comparing women to men; compared to those aged <30 years the PR (95% CI)
      was 0.70 (0.57-0.86), 0.70 (0.58-0.85) and 0.78 (0.63-0.96) for age 30-39, 40-49
      and >=50 years respectively, p for trend = 0.03; compared to those who were
      normal weight, the PR was 0.93 (0.79-1.10) and 0.90 (0.74-1.09) for overweight
      and obese persons respectively, p = 0.26. The PR for age was attenuated to non
      significant levels in multivariable analyses. Being married was a statistically
      significant correlate of higher physical activity levels, the PR comparing
      unmarried to married persons in multivariate analysis was 0.81 (0.67-0.97), p =
      0.03. CONCLUSIONS: More than 80% of urban, professional Nigerian adults do not
      meet the WHO recommendations of physical activity. Urbanized Africans in this
      study population had low levels of leisure-time physical activity, independent of
      age, sex and body-mass index. This has major implications for the prevalence of
      non-communicable diseases in this population.

PMID- 24885081
TI  - Why alternative teenagers self-harm: exploring the link between non-suicidal self
      injury, attempted suicide and adolescent identity.
AB  - BACKGROUND: The term 'self-harm' encompasses both attempted suicide and non
      suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or
      sexual minorities, and more controversially, those who identify as 'Alternative'
      (Goth, Emo) have been proposed as being more likely to self-harm, while other
      groups such as 'Jocks' are linked with protective coping behaviours (for example
      exercise). NSSI has autonomic (it reduces negative emotions) and social (it
      communicates distress or facilitates group 'bonding') functions. This study
      explores the links between such aspects of self-harm, primarily NSSI, and youth
      subculture. METHODS: An anonymous survey was carried out of 452 15 year old
      German school students. Measures included: identification with different youth
      cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic);
      social background, e.g. socioeconomic status; and experience of victimisation.
      Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire
      and the Functional Assessment of Self-Mutilation (FASM). RESULTS: An
      "Alternative" identity was directly (r ~ 0.3) and a "Jock" identity inversely (r
      ~ -0.1) correlated with self-harm. "Alternative" teenagers self-injured more
      frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4-8 times
      more likely to attempt suicide (even after adjusting for social background) than
      their non-Alternative peers. They were also more likely to self-injure for
      autonomic, communicative and social reasons than other adolescents. CONCLUSIONS:
      About half of 'Alternative' adolescents' self-injure, primarily to regulate
      emotions and communicate distress. However, a minority self-injure to reinforce
      their group identity, i.e. 'To feel more a part of a group'.

PMID- 24885083
TI  - Identification of candidate genes and molecular markers for heat-induced brown
      discoloration of seed coats in cowpea [Vigna unguiculata (L.) Walp].
AB  - BACKGROUND: Heat-induced browning (Hbs) of seed coats is caused by high
      temperatures which discolors the seed coats of many legumes, affecting the visual
      appearance and quality of seeds. The genetic determinants underlying Hbs in
      cowpea are unknown. RESULTS: We identified three QTL associated with the heat
      induced browning of seed coats trait, Hbs-1, Hbs-2 and Hbs-3, using cowpea RIL
      populations IT93K-503-1 (Hbs positive) x CB46 (hbs negative) and IT84S-2246 (Hbs
      positive) x TVu14676 (hbs negative). Hbs-1 was identified in both populations,
      accounting for 28.3% -77.3% of the phenotypic variation. SNP markers 1_0032 and
      1_1128 co-segregated with the trait. Within the syntenic regions of Hbs-1 in
      soybean, Medicago and common bean, several ethylene forming enzymes, ethylene
      responsive element binding factors and an ACC oxidase 2 were observed. Hbs-1 was
      identified in a BAC clone in contig 217 of the cowpea physical map, where
      ethylene forming enzymes were present. Hbs-2 was identified in the IT93K-503-1 x
      CB46 population and accounted for of 9.5 to 12.3% of the phenotypic variance. Hbs
      3 was identified in the IT84S-2246 x TVu14676 population and accounted for 6.2 to
      6.8% of the phenotypic variance. SNP marker 1_0640 co-segregated with the heat
      induced browning phenotype. Hbs-3 was positioned on BAC clones in contig512 of
      the cowpea physical map, where several ACC synthase 1 genes were present.
      CONCLUSION: The identification of loci determining heat-induced browning of seed
      coats and co-segregating molecular markers will enable transfer of hbs alleles
      into cowpea varieties, contributing to higher quality seeds.

PMID- 24885082
TI  - Molecular mechanisms of nutlin-3 involve acetylation of p53, histones and heat
      shock proteins in acute myeloid leukemia.
AB  - BACKGROUND: The small-molecule MDM2 antagonist nutlin-3 has proved to be an
      effective p53 activating therapeutic compound in several preclinical cancer
      models, including acute myeloid leukemia (AML). We and others have previously
      reported a vigorous acetylation of the p53 protein by nutlin-treatment. In this
      study we aimed to investigate the functional role of this p53 acetylation in
      nutlin-sensitivity, and further to explore if nutlin-induced protein acetylation
      in general could indicate novel targets for the enhancement of nutlin-based
      therapy. RESULTS: Nutlin-3 was found to enhance the acetylation of p53 in the
      human AML cell line MOLM-13 (wild type TP53) and in TP53 null cells transfected
      with wild type p53 cDNA. Stable isotope labeling with amino acids in cell culture
      (SILAC) in combination with immunoprecipitation using an anti-acetyl-lysine
      antibody and mass spectrometry analysis identified increased levels of acetylated
      Histone H2B, Hsp27 and Hsp90 in MOLM-13 cells after nutlin-treatment, accompanied
      by downregulation of total levels of Hsp27 and Hsp90. Intracellular levels of
      heat shock proteins Hsp27, Hsp40, Hsp60, Hsp70 and Hsp90alpha were correlated to
      nutlin-sensitivity for primary AML cells (n = 40), and AML patient samples with
      low sensitivity to nutlin-3 tended to express higher levels of heat shock
      proteins than more responsive samples. Combination therapy of nutlin-3 and Hsp90
      inhibitor geldanamycin demonstrated synergistic induction of apoptosis in AML
      cell lines and primary AML cells. Finally, TP53 null cells transfected with a p53
      acetylation defective mutant demonstrated decreased heat shock protein
      acetylation and sensitivity to nutlin-3 compared to wild type p53 expressing
      cells. CONCLUSIONS: Altogether, our results demonstrate that nutlin-3 induces
      acetylation of p53, histones and heat shock proteins, and indicate that p53
      acetylation status and the levels of heat shock proteins may participate in
      modulation of nutlin-3 sensitivity in AML.

PMID- 24885084
TI  - Evaluating the feasibility of using insecticide quantification kits (IQK) for
      estimating cyanopyrethroid levels for indoor residual spraying in Vanuatu.
AB  - BACKGROUND: The quality of routine indoor residual spraying (IRS) operations is
      rarely assessed because of the limited choice of methods available for
      quantifying insecticide content in the field. This study, therefore, evaluated a
      user-friendly, rapid colorimetric assay for detecting insecticide content after
      routine IRS operations were conducted. METHODS: This study was conducted in Tafea
      Province, Vanuatu. Routine IRS was conducted with lambda cyhalothrin. Two methods
      were used to quantify the IRS activities: 1) pre-spray application of small felt
      pads and 2) post-spray removal of insecticide with adhesive. The insecticide
      content was quantified using a colorimetric assay (Insecticide Quantification Kit
      [IQK]), which involved exposing each sample to the test reagents for 15 mins. The
      concentration of insecticide was indicated by the depth of red colour. RESULTS:
      The IQK proved simple to perform in the field and results could be immediately
      interpreted by the programme staff. The insecticide content was successfully
      sampled by attaching felt pads to the house walls prior to spraying. The IRS
      operation was well conducted, with 83% of houses being sprayed at the target dose
      (20 - 30 mg AI/m2). The average reading across all houses was 24.4 +/- 1.5 mg
      AI/m2. The results from the felt pads applied pre-spray were used as a base to
      compare methods for sampling insecticide from walls post-spray. The adhesive of
      Sellotape did not collect adequate samples. However, the adhesive of the felt
      pads provided accurate samples of the insecticide content on walls. CONCLUSION:
      The IQK colorimetric assay proved to be a useful tool that was simple to use
      under realistic field conditions. The assay provided rapid information on IRS
      spray dynamics and spray team performance, facilitating timely decision making
      and reporting for programme managers. The IQK colorimetric assay will have direct
      applications for routine quality control in malaria control programmes globally
      and has the potential to improve the efficacy of vector control operations.

PMID- 24885085
TI  - A common-garden experiment to quantify evolutionary processes in copepods: the
      case of emamectin benzoate resistance in the parasitic sea louse Lepeophtheirus
      salmonis.
AB  - BACKGROUND: The development of pesticide resistance represents a global challenge
      to food production. Specifically for the Atlantic salmon aquaculture industry,
      parasitic sea lice and their developing resistance to delousing chemicals is
      challenging production. In this study, seventeen full sibling families,
      established from three strains of Lepeophtheirus salmonis displaying differing
      backgrounds in emamectin benzoate (EB) tolerance were produced and quantitatively
      compared under a common-garden experimental design. Lice surviving to the
      preadult stage were then exposed to EB and finally identified through the
      application of DNA parentage testing. RESULTS: With the exception of two families
      (19 and 29%), survival from the infectious copepod to preadult stage was very
      similar among families (40-50%). In contrast, very large differences in survival
      following EB exposure were observed among the families (7.9-74%). Family survival
      post EB exposure was consistent with the EB tolerance characteristics of the
      strains from which they were established and no negative effect on infection
      success were detected in association with increased EB tolerance. Two of the lice
      families that displayed reduced sensitivity to EB were established from a
      commercial farm that had previously used this chemical. This demonstrates that
      resistant alleles were present on this farm even though the farm had not reported
      treatment failure. CONCLUSIONS: To our knowledge, this represents the first study
      where families of any multi-cellular parasite have been established and compared
      in performance under communal rearing conditions in a common-garden experiment.
      The system performed in a predictable manner and permitted, for the first time,
      elucidation of quantitative traits among sea lice families. While this experiment
      concentrated on, and provided a unique insight into EB sensitivity among lice
      families, the experimental design represents a novel methodology to
      experimentally address both resistance development and other evolutionary
      questions in parasitic copepods.

PMID- 24885086
TI  - The efficacy of stereotactic body radiation therapy on huge hepatocellular
      carcinoma unsuitable for other local modalities.
AB  - BACKGROUND AND AIM: To evaluate the safety and efficacy of Cyberknife
      stereotactic body radiation therapy (SBRT) and its effect on survival in patients
      with unresectable huge hepatocellular carcinoma (HCC) unsuitable of other
      standard treatment option. METHODS: Between 2009 and 2011, 22 patients with
      unresectable huge HCC (?10 cm) were treated with SBRT. dose ranged from 26 Gy to
      40 Gy in five fractions. Overall survival (OS) and disease-progression free
      survival (DPFS) were determined by Kaplan-Meier analysis. Tumor response and
      toxicities were also assessed. RESULTS: After a median follow-up of 11.5 month
      (range 2-46 months). The objective response rate was achieved in 86.3% (complete
      response (CR): 22.7% and partial response (PR): 63.6%). The 1-yr. local control
      rate was 55.56%. The 1-year OS was 50% and median survival was 11 months (range 2
      46 months). In univariate analysis, Child-Pugh stage (p = 0.0056) and SBRT dose
      (p = 0.0017) were significant factors for survival. However, in multivariate
      analysis, SBRT dose (p = 0.0072) was the most significant factor, while Child
      Pugh stage of borderline significance. (p = 0.0514). Acute toxicities were mild
      and well tolerated. CONCLUSION: This study showed that SBRT can be delivered
      safely to huge HCC and achieved a substantial tumor regression and survival. The
      results suggest this technique should be considered a salvage treatment. However,
      local and regional recurrence remain the major cause of failure. Further studies
      of combination of SBRT and other treatment modalities may be reasonable.

PMID- 24885087
TI  - Erythrodermic psoriasis with bullous pemphigoid: combination treatment with
      methotrexate and compound glycyrrhizin.
AB  - We report a case of erythrodermic psoriasis with bullous pemphigoid (BP) in a 68
      year-old male. The patient had a history of psoriasis for 35 years and tense,
      blisterlike lesions for 4 months. He presented with diffuse flushing,
      infiltrative swelling, and tense blisterlike lesions on his head, trunk, and
      limbs. This patient was successfully treated by a combination of methotrexate and
      compound glycyrrhizin. We also discuss the clinical manifestations,
      histopathological features, and differentiation of erythrodermic psoriasis with
      BP and present a review of the pertinent literature. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1853737109114076.

PMID- 24885088
TI  - Characterization of Aspergillus species on Brazil nut from the Brazilian
      Amazonian region and development of a PCR assay for identification at the genus
      level.
AB  - BACKGROUND: Brazil nut is a protein-rich extractivist tree crop in the Amazon
      region. Fungal contamination of shells and kernel material frequently includes
      the presence of aflatoxigenic Aspergillus species from the section Flavi.
      Aflatoxins are polyketide secondary metabolites, which are hepatotoxic
      carcinogens in mammals. The objectives of this study were to identify Aspergillus
      species occurring on Brazil nut grown in different states in the Brazilian Amazon
      region and develop a specific PCR method for collective identification of member
      species of the genus Aspergillus. RESULTS: Polyphasic identification of 137
      Aspergillus strains isolated from Brazil nut shell material from cooperatives
      across the Brazilian Amazon states of Acre, Amapa and Amazonas revealed five
      species, with Aspergillus section Flavi species A. nomius and A. flavus the most
      abundant. PCR primers ASP_GEN_MTSSU_F1 and ASP_GEN_MTSSU_R1 were designed for the
      genus Aspergillus, targeting a portion of the mitochondrial small subunit
      ribosomal RNA gene. Primer specificity was validated through both electronic PCR
      against target gene sequences at Genbank and in PCR reactions against DNA from
      Aspergillus species and other fungal genera common on Brazil nut. Collective
      differentiation of the observed section Flavi species A. flavus, A. nomius and A.
      tamarii from other Aspergillus species was possible on the basis of RFLP
      polymorphism. CONCLUSIONS: Given the abundance of Aspergillus section Flavi
      species A. nomius and A. flavus observed on Brazil nut, and associated risk of
      mycotoxin accumulation, simple identification methods for such mycotoxigenic
      species are of importance for Hazard Analysis Critical Control Point system
      implementation. The assay for the genus Aspergillus represents progress towards
      specific PCR identification and detection of mycotoxigenic species.

PMID- 24885089
TI  - Total cost estimation for implementing genome-enabled selection in a multi-level
      swine production system.
AB  - BACKGROUND: Determining an animal's genetic merit using genomic information can
      improve estimated breeding value (EBV) accuracy; however, the magnitude of the
      accuracy improvement must be large enough to recover the costs associated with
      implementing genome-enabled selection. One way to reduce costs is to genotype
      nucleus herd selection candidates using a low-density chip and to use high
      density chip genotyping for animals that are used as parents in the nucleus
      breeding herd. The objective of this study was to develop a tool to estimate the
      cost structure associated with incorporating genome-enabled selection into multi
      level commercial breeding programs. RESULTS: For the purpose of this
      deterministic study, it was assumed that a commercial pig is created from a
      terminal line sire and a dam that is a cross between two maternal lines. It was
      also assumed that all male and female selection candidates from the 1000 sow
      maternal line nucleus herds were genotyped at low density and all animals used
      for breeding at high density. With the assumptions used in this analysis, it was
      estimated that genome-enabled selection costs for a maternal line would be
      approximately US$0.082 per weaned pig in the commercial production system. A
      total of US$0.164 per weaned pig is needed to incorporate genome-enabled
      selection into the two maternal lines. Similarly, for a 600 sow terminal line
      nucleus herd and genotyping only male selection candidates with the low-density
      panel, the cost per weaned pig in the commercial herd was estimated to be
      US$0.044. This means that US$0.21 per weaned pig produced at the commercial level
      and sired by boars obtained from the nucleus herd breeding program needs to be
      added to the genetic merit value in order to break even on the additional cost
      required when genome-enabled selection is used in both maternal lines and the
      terminal line. CONCLUSIONS: By modifying the input values, such as herd size and
      genotyping strategy, a flexible spreadsheet tool developed from this work can be
      used to estimate the additional costs associated with genome-enabled selection.
      This tool will aid breeders in estimating the economic viability of incorporating
      genome-enabled selection into their specific breeding program.

PMID- 24885090
TI  - Fast multiclonal clusterization of V(D)J recombinations from high-throughput
      sequencing.
AB  - BACKGROUND: V(D)J recombinations in lymphocytes are essential for immunological
      diversity. They are also useful markers of pathologies. In leukemia, they are
      used to quantify the minimal residual disease during patient follow-up. However,
      the full breadth of lymphocyte diversity is not fully understood. RESULTS: We
      propose new algorithms that process high-throughput sequencing (HTS) data to
      extract unnamed V(D)J junctions and gather them into clones for quantification.
      This analysis is based on a seed heuristic and is fast and scalable because in
      the first phase, no alignment is performed with germline database sequences. The
      algorithms were applied to TR gamma HTS data from a patient with acute
      lymphoblastic leukemia, and also on data simulating hypermutations. Our methods
      identified the main clone, as well as additional clones that were not identified
      with standard protocols. CONCLUSIONS: The proposed algorithms provide new insight
      into the analysis of high-throughput sequencing data for leukemia, and also to
      the quantitative assessment of any immunological profile. The methods described
      here are implemented in a C++ open-source program called Vidjil.

PMID- 24885091
TI  - BLASTGrabber: a bioinformatic tool for visualization, analysis and sequence
      selection of massive BLAST data.
AB  - BACKGROUND: Advances in sequencing efficiency have vastly increased the sizes of
      biological sequence databases, including many thousands of genome-sequenced
      species. The BLAST algorithm remains the main search engine for retrieving
      sequence information, and must consequently handle data on an unprecedented
      scale. This has been possible due to high-performance computers and parallel
      processing. However, the raw BLAST output from contemporary searches involving
      thousands of queries becomes ill-suited for direct human processing. Few programs
      attempt to directly visualize and interpret BLAST output; those that do often
      provide a mere basic structuring of BLAST data. RESULTS: Here we present a
      bioinformatics application named BLASTGrabber suitable for high-throughput
      sequencing analysis. BLASTGrabber, being implemented as a Java application, is OS
      independent and includes a user friendly graphical user interface. Text or XML
      formatted BLAST output files can be directly imported, displayed and categorized
      based on BLAST statistics. Query names and FASTA headers can be analysed by text
      mining. In addition to visualizing sequence alignments, BLAST data can be ordered
      as an interactive taxonomy tree. All modes of analysis support selection, export
      and storage of data. A Java interface-based plugin structure facilitates the
      addition of customized third party functionality. CONCLUSION: The BLASTGrabber
      application introduces new ways of visualizing and analysing massive BLAST output
      data by integrating taxonomy identification, text mining capabilities and generic
      multi-dimensional rendering of BLAST hits. The program aims at a non-expert
      audience in terms of computer skills; the combination of new functionalities
      makes the program flexible and useful for a broad range of operations.

PMID- 24885092
TI  - Failure of a dietary model to affect markers of inflammation in domestic cats.
AB  - BACKGROUND: Oxidative stress and inflammation can be altered by dietary factors
      in various species. However, little data are available in true carnivorous
      species such as domestic cats. As numerous anti-inflammatory and anti-oxidative
      additives become available and might be of use in cats with chronic low-grade
      inflammatory diseases, the current study aimed to develop a model of diet-induced
      inflammation by use of two opposite diets. It was hypothesized that a high fat
      diet enhanced in n-6 PUFA and with lower concentrations of antioxidants would
      evoke inflammation and oxidative stress in domestic cats. RESULTS: Sixteen
      healthy adult cats were allocated to two groups. One group received a moderate
      fat diet, containing pork lard and salmon oil (AA:(EPA + DHA) ratio 0.19) (MFn
      3), while the other group was fed a high fat diet, containing pork lard and
      chicken fat (AA:(EPA + DHA) ratio 2.06) (HFn-6) for 12 weeks. Prior to and 2, 4,
      6, 8, 10 and 12 weeks after starting the testing period, blood samples were
      collected. Erythrocytic fatty acid profile showed clear alterations in accordance
      to the dietary fatty acid profile. Serum thiobarbituric acid reactive substances
      was higher when fed MFn-3 compared to the HFn-6, suggesting augmented oxidative
      stress. This was associated with a reduced serum vitamin E status, as serum alpha
      tocopherol concentrations were lower with MFn-3, even with higher dietary levels
      of vitamin E. Serum cytokine and serum amyloid A concentrations were not
      influenced by diet. CONCLUSION: These results point towards a resistance of cats
      to develop dietary fat-induced inflammation, but also suggest a high
      susceptibility to oxidative stress when fed a fish oil-supplemented diet even
      with moderate fat level and additional vitamin E.

PMID- 24885093
TI  - Quantitative analysis of castration resistant prostate cancer progression through
      phosphoproteome signaling.
AB  - BACKGROUND: Although recent progress has been made in treating castration
      resistant prostate cancer, the interplay of signaling pathways which enable
      castration resistant growth is incompletely understood. A data driven,
      multivariate approach, was used in this study to predict prostate cancer cell
      survival based on the phosphorylation levels of key proteins in PC3, LNCaP, and
      MDA-PCa-2b cell lines in response to EGF, IGF1, IL6, TNFalpha,
      dihydrotestosterone, and docetaxel treatment. METHODS: The prostate cancer cell
      lines were treated with ligands or inhibitors, cell lyates were collected, and
      the amount of phosphoprotein quantified using 384 well ELISA assays. In separate
      experiments, relative cell viability was determined using an MTT assay.
      Normalized data was imported into Matlab where regression analysis was performed.
      RESULTS: Based on a linear model developed using partial least squares
      regression, p-Erk1/2 was found to correlate with castration resistant survival
      along with p-RPS6, and this model was determined to have a leave-one-out cross
      validated R2 value of 0.61. The effect of androgen on the phosphoproteome was
      examined, and increases in PI3K related phosphoproteins (p-Akt, p-RPS6, and p
      GSK3) were observed which accounted for the majority of the significant increase
      in androgen-mediated cell survival. Simultaneous inhibition of the PI3K pathway
      and treatment with androgen resulted in a non-significant increase in survival.
      Given the strong effect of PI3K related signaling in enabling castration
      resistant survival, the specific effect of mTor versus complete inhibition was
      examined using targeted inhibitors. It was determine that mTor inhibition
      accounts for 52% of the effect of complete PI3K inhibition on cell survival. The
      differences in signaling between the cell lines were explored it was observed
      that MDA-PCa-2b exhibited far less activation of p-Erk in response to varying
      treatments, explaining one of the reasons for the lack of castration resistance.
      CONCLUSION: In this work, regression analysis to the phosphoproteome was used to
      illustrate the sources of castration resistance between the cell lines including
      reduced p-Erk signaling in MDA-PCa-2b and variations in p-JNK across the cell
      lines, as well as studying the signaling pathways which androgen acts through,
      and determining the response to treatment with targeted inhibitors.

PMID- 24885094
TI  - Recurrent wheezing is associated with intestinal protozoan infections in Warao
      Amerindian children in Venezuela: a cross-sectional survey.
AB  - BACKGROUND: While in developed countries the prevalence of allergic diseases is
      rising, inflammatory diseases are relatively uncommon in rural developing areas.
      High prevalence rates of helminth and protozoan infections are commonly found in
      children living in rural settings and several studies suggest an inverse
      association between helminth infections and allergies. No studies investigating
      the relationship between parasitic infections and atopic diseases in rural
      children of developing countries under the age of 2 years have been published so
      far. We performed a cross-sectional survey to investigate the association of
      helminth and protozoan infections and malnutrition with recurrent wheezing and
      atopic eczema in Warao Amerindian children in Venezuela. METHODS: From August to
      November 2012, 229 children aged 0 to 2 years residing in the Orinoco Delta in
      Venezuela were enrolled. Data were collected through standardized questionnaires
      and physical examination, including inspection of the skin and anthropometric
      measurements. A stool sample was requested from all participants and detection of
      different parasites was performed using microscopy and real time polymerase chain
      reaction (PCR). RESULTS: We observed high prevalence rates of atopic eczema and
      recurrent wheezing, respectively 19% and 23%. The prevalence of helminth
      infections was 26% and the prevalence of protozoan infections was 59%. Atopic
      eczema and recurrent wheezing were more frequently observed in stunted compared
      with non-stunted children in multivariable analysis (OR 4.3, 95% CI 1.3 - 13.6, p
      = 0.015 and OR 4.5, 95% CI 0.97 - 21.2, p = 0.055). Furthermore, recurrent
      wheezing was significantly more often observed in children with protozoan
      infections than in children without protozoan infections (OR 6.7, 95% CI 1.5 -
      30.5). CONCLUSIONS: High prevalence rates of atopic eczema and recurrent wheezing
      in Warao Amerindian children under 2 years of age were related to stunting and
      intestinal protozoan infections respectively. Helminth infections were not
      significantly associated with either atopic eczema or recurrent wheezing.

PMID- 24885095
TI  - Time-course changes in left ventricular myocardial deformation in STZ-induced
      rabbits on velocity vector imaging.
AB  - OBJECTIVES: To clarify the time-course changes in left ventricular myocardial
      deformation using velocity vector imaging and to provide insights into our
      understanding of the cardiac pathophysiology in diabetes mellitus. METHODS:
      Thirty New Zealand white rabbits were randomly divided into either the control
      group (n = 10) or the diabetes mellitus (DM) group (induced with STZ, n = 20).
      For the myocardial deformation studies, echocardiography and syngo-vector
      velocity imaging (VVI) were performed at baseline and after 2, 4, 8, and 12 weeks
      in all of the rabbits. The left ventricular (LV) global longitudinal and
      circumferential strain and strain rate were measured. For histomorphological
      study of the heart structure, 2 of the STZ-induced rabbits were killed at 2, 4,
      8, and 12 weeks. Routine hematoxylin and eosin staining was performed. RESULTS:
      At 2 weeks, the global longitudinal strain (GLS), systolic strain rate (GLSRs),
      and diastolic strain rate (GLSRd) were significantly lower in the DM group
      compared with the control group (-18.16% versus -24.00%, -1.86 s(-1) versus -2.49
      s(-1), 1.93 s(-1) versus 2.42 s(-1), respectively, P < 0.05), while, compared
      with the control group, the global circumferential strain (GCS), systolic strain
      rate (GCSRs), and diastolic strain rate (GCSRd) in the DM group were
      significantly decreased (-12.77% versus -23.31%, -1.31 s(-1) versus -2.20 s(-1),
      1.41 s(-1) versus 2.15 s(-1), respectively, P < 0.05) at 8 weeks. With the
      progression of untreated diabetes, the histoanatomical alterations intensified
      gradually beginning at 2 weeks. CONCLUSIONS: The progressive impairments in LV
      myocardial deformation and structure occurred early in diabetic rabbits with
      normal LV ejection fraction (EF), FS, and E/A. VVI could be used to evaluate
      subtle cardiac dysfunction in the early phase of DM.

PMID- 24885096
TI  - A monitoring and feedback tool embedded in a counselling protocol to increase
      physical activity of patients with COPD or type 2 diabetes in primary care: study
      protocol of a three-arm cluster randomised controlled trial.
AB  - BACKGROUND: Physical activity is important for a healthy lifestyle. Although
      physical activity can delay complications and decrease the burden of the disease,
      the level of activity of patients with chronic obstructive pulmonary disease
      (COPD) or type 2 Diabetes Mellitus (DM2) is often far from optimal. To stimulate
      physical activity, a monitoring and feedback tool, consisting of an accelerometer
      linked to a smart phone and webserver (It's LiFe! tool), and a counselling
      protocol for practice nurses in primary care was developed (the Self-management
      Support Program). The main objective of this study is to measure the longitudinal
      effects of this counselling protocol and the added value of using the tool.
      METHODS/DESIGN: This three-armed cluster randomised controlled trial with 120
      participants with COPD and 120 participants with DM2 (aged 40-70), compares the
      counselling protocol with and without the use of the tool (group 1 and 2) with
      usual care (group 3). Recruitment takes place at GP practices in the southern
      regions of the Netherlands. Randomisation takes place at the practice level. The
      intended sample (three arms of 8 practices) powers the study to detect a 10
      minute difference of moderate and intense physical activity per day between
      groups 1 and 3. Participants in the intervention groups have to visit the
      practice nurse 3-4 times for physical activity counselling, in a 4-6-month
      period. Specific activity goals tailored to the individual patient's preferences
      and needs will be set. In addition, participants in group 1 will be instructed to
      use the tool in daily life. The primary outcome, physical activity, will be
      measured in all groups with a physical activity monitor (PAM). Secondary outcomes
      are quality of life, general - and exercise - self-efficacy, and health status.
      Follow-up will take place after 6 and 9 months. Separately, a process evaluation
      will be conducted to explore reasons for trial non-participation, and the
      intervention's acceptability for participating patients and nurses. DISCUSSION:
      Results of this study will give insight into the effects of the It's LiFe!
      monitoring and feedback tool combined with care from a practice nurse for people
      with COPD or DM2 on physical activity. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01867970.

PMID- 24885097
TI  - Strain- and defect-mediated thermal conductivity in silicon nanowires.
AB  - The unique thermal transport of insulating nanostructures is attributed to the
      convergence of material length scales with the mean free paths of quantized
      lattice vibrations known as phonons, enabling promising next-generation thermal
      transistors, thermal barriers, and thermoelectrics. Apart from size, strain and
      defects are also known to drastically affect heat transport when introduced in an
      otherwise undisturbed crystalline lattice. Here we report the first experimental
      measurements of the effect of both spatially uniform strain and point defects on
      thermal conductivity of an individual suspended nanowire using in situ Raman
      piezothermography. Our results show that whereas phononic transport in undoped Si
      nanowires with diameters in the range of 170-180 nm is largely unaffected by
      uniform elastic tensile strain, another means of disturbing a pristine lattice,
      namely, point defects introduced via ion bombardment, can reduce the thermal
      conductivity by over 70%. In addition to discerning surface- and core-governed
      pathways for controlling thermal transport in phonon-dominated insulators and
      semiconductors, we expect our novel approach to have broad applicability to a
      wide class of functional one- and two-dimensional nanomaterials. 

PMID- 24885098
TI  - Collision tumor of low-grade B-cell lymphoma and adenocarcinoma with tuberculosis
      in the colon: a case report and literature review.
AB  - This report presents a case of collision tumors of low-grade B-cell lymphoma and
      adenocarcinoma in the sigmoid colon of an 81-year-old man. All surgically
      resected regional mesenteric lymph nodes were found to be occupied by low-grade B
      cell lymphoma, and one lymph node showed the presence of adenocarcinoma. Low
      grade B-cell lymphoma was also observed in the resected spleen. Moreover,
      concurrent tuberculosis infection in the resected colon was proven by the
      presence of positive results obtained with polymerase chain reaction analysis of
      the mycobacterial DNA. Systemic chemotherapy was administered for advanced colon
      cancer with lung metastasis, and anti-tuberculosis treatment was also prescribed.
      The occurrence of synchronous lymphoma and adenocarcinoma of the colorectal
      region is rare. Furthermore, collisions of these different entities are also
      extremely unusual. The accurate clinical determination of the dominant tumor and
      a timely follow-up are required for the proper treatment of these cases. 

PMID- 24885099
TI  - Screening premorbid metabolic syndrome in community pharmacies: a cross-sectional
      descriptive study.
AB  - BACKGROUND: Premorbid metabolic syndrome (pre-MetS) is a cluster of
      cardiometabolic risk factors characterised by central obesity, elevated fasting
      glucose, atherogenic dyslipidaemia and hypertension without established
      cardiovascular disease or diabetes. Community pharmacies are in an excellent
      position to develop screening programmes because of their direct contact with the
      population.The main aim of the study was to determine the prevalence of pre-MetS
      in people who visited community pharmacies for measurement of any of its five
      risk factors to detect the presence of other risk factors. The secondary aims
      were to study the presence of other cardiovascular risk factors and determine
      patients' cardiovascular risk. METHODS: Cross-sectional, descriptive, multicentre
      study. Patients meeting selection criteria aged between 18 and 65 years who
      visited participating community pharmacies to check any of five pre-MetS
      diagnostic factors were included.The study involved 23 community pharmacies in
      Catalonia (Spain). Detection criteria for pre-MetS were based on the WHO proposal
      following IDF and AHA/NHBI consensus. Cardiovascular risk (CVR) was calculated by
      Regicor and Score methods. Other variables studied were smoking habit, physical
      activity, body mass index (BMI), and pharmacological treatment of dyslipidemia
      and hypertension. The data were collected and analysed with the SPSS programme.
      Comparisons of variables were carried out using the Student's T-test, Chi-Squared
      test or ANOVA test. Level of significance was 5% (0.05). RESULTS: The overall
      prevalence of pre-MetS was 21.9% [95% CI 18.7-25.2]. It was more prevalent in
      men, 25.5% [95% CI 22.1-28.9], than in women, 18.6% [95% CI 15.5-21.7], and
      distribution increased with age. The most common risk factors were high blood
      pressure and abdominal obesity. About 70% of people with pre-MetS were sedentary
      and over 85% had a BMI >=25 Kg/m2. Some 22.4% had two metabolic criteria and
      27.2% of patients with pre-MetS had no previous diagnosis. CONCLUSIONS: The
      prevalence of pre-MetS in our study (21.9%) was similar to that found in other
      studies carried out in Primary Care in Spain. The results of this study confirm
      emergent cardiometabolic risk factors such as hypertension, obesity and physical
      inactivity.Our study highlights the strategic role of the community pharmacy in
      the detection of pre-MetS in the apparently healthy population.

PMID- 24885100
TI  - Primary prevention in general practice - views of German general practitioners: a
      mixed-methods study.
AB  - BACKGROUND: Policy efforts focus on a reorientation of health care systems
      towards primary prevention. To guide such efforts, we analyzed the role of
      primary prevention in general practice and general practitioners' (GPs) attitudes
      toward primary prevention. METHODS: Mixed-method study including a cross
      sectional survey of all community-based GPs and focus groups in a sample of GPs
      who collaborated with the Institute of General Practice in Berlin, Germany in
      2011. Of 1168 GPs 474 returned the mail survey. Fifteen GPs participated in focus
      group discussions. Survey and interview guidelines were developed and tested to
      assess and discuss beliefs, attitudes, and practices regarding primary
      prevention. RESULTS: Most respondents considered primary prevention within their
      realm of responsibility (70%). Primary prevention, especially physical activity,
      healthy eating, and smoking cessation, was part of the GPs' health care
      recommendations if they thought it was indicated. Still a quarter of survey
      respondents discussed reduction of alcohol consumption with their patients
      infrequently even when they thought it was indicated. Similarly 18% claimed that
      they discuss smoking cessation only sometimes. The focus groups revealed that GPs
      were concerned about the detrimental effects an uninvited health behavior
      suggestion could have on patients and were hesitant to take on the role of
      "health policing". GPs saw primary prevention as the responsibility of multiple
      actors in a network of societal and municipal institutions. CONCLUSIONS: The
      mixed-method study showed that primary prevention approaches such as lifestyle
      counseling is not well established in primary care. GPs used a selective approach
      to offer preventive advice based upon indication. GPs had a strong sense that a
      universal prevention approach carried the potential to destroy a good patient
      physician relationship. Other approaches to public health may be warranted such
      as a multisectoral approach to population health. This type of restructuring of
      the health care sector may benefit patients who are unable to afford specific
      prevention programmes and who have competing demands that hinder their ability to
      focus on behavior change.

PMID- 24885101
TI  - An evaluation of a tailored intervention on village doctors use of electronic
      health records.
AB  - BACKGROUND: To describe and evaluate the effectiveness of tailored intervention
      on village doctor's use of electronic health records (EHR) in rural community
      health services in less developed areas. METHODS: Ten townships were selected. In
      each township, two similar health service station (CHSS) were chosen. One was
      randomly as allocated to the intervention group, the other to the control group.
      Over six monthly visits, a structured on-site intervention including education,
      supervision and technical support was provided to village doctors in the
      intervention group tailored to their needs. The Control group received no visits.
      A sample of 20 families from each CHSS was randomly chosen. An online evaluation
      of each family's EHR was conducted by the investigators at baseline and at the
      end of the 6 month intervention. RESULTS: In the intervention group, the
      proportion of households with complete records increased: basic personal
      information from 2.6% to 32.5%, (Z = -15.099, P = 0.000) and health education
      records from 0.3% to 1.6% (Z = -4.459, P = 0.000). Similarly at baseline none of
      the 80 elders had her records. This increased in the intervention group to 16.4%
      recorded in part and 37.0% in full (Z = -7.480, P = 0.000). The proportion of
      complete health management records for children aged 1 to 2 years and 3 to 6
      years increased from 28.6% and 33.3% to 66.7% and 74.2% respectively (the
      difference of children group 3 to 6 years of age was statistically significant, Z
      = -3.860, p = 0.000). The proportion of complete basic clinic records in the
      intervention group increased from 7.6% to 13.9% (Z = -3.252, P = 0.001). There
      were no significant differences in the control group. CONCLUSIONS: The pilot
      study showed that a on-site education, supervision and technical support tailored
      to their needs was associated with improvements in village doctors use of EHR.
      This model is worthy of implementation in other rural areas.

PMID- 24885102
TI  - Testicular histological and immunohistochemical aspects in a post-pubertal
      patient with 5 alpha-reductase type 2 deficiency: case report and review of the
      literature in a perspective of evaluation of potential fertility of these
      patients.
AB  - BACKGROUND: Testicular morphology and immunohistochemical studies have never been
      reported in genetically documented adult patients with 5 alpha-reductase type 2
      deficiency (5alpha-R2 deficiency). CASE PRESENTATION: We describe the testicular
      histopathology of a 17-year-old XY subject with 5alpha-R2 deficiency caused by
      the recurrent homozygous Gly115Asp loss of function mutation of the SRD5A2
      gene.We also performed an immunohistochemical analysis in order to further study
      the relationship between seminiferous tubules structure, Sertoli cell
      differentiation and androgenic signaling impairment in this case. We thus
      evaluated the testicular expression of the anti-Mullerian hormone (AMH), androgen
      receptor (AR) and 3beta-hydroxysteroid dehydrogenase (3betaHSD). Histological
      analysis revealed a heterogeneous aspect with a majority (92%) of seminiferous
      tubules (ST) presenting a mature aspect but containing only Sertoli cells and
      devoid of germ cells and spermatogenesis. Focal areas of immature ST (8%) were
      also found. Testicular AR and 3betaHSD expression were detected in adult male
      control, 5alpha-R2 deficiency and CAIS subjects. However, AMH expression was
      heterogeneous (detectable only in few AR negative prepubertal ST, but otherwise
      repressed) in the 5alpha-R2 deficiency, conversely to normal adult testis in
      which AMH was uniformly repressed and to an adult CAIS testis in which AMH was
      uniformly and strongly expressed. CONCLUSION: Intratesticular testosterone can
      repress AMH by itself, independently of its metabolism into dihydrotestosterone.
      We also compare our results to the few post pubertal cases of 5alpha-R2
      deficiency with available histological testicular description, reported in the
      literature. We will discuss these histological findings, in the more general
      context of evaluating the fertility potential of these patients if they were
      raised as males and were azoospermic.

PMID- 24885103
TI  - Evaluation of the quality of antenatal care using electronic health record
      information in family medicine clinics of Mexico City.
AB  - BACKGROUND: Evaluation of the quality of antenatal care (ANC) using indicators
      should be part of the efforts to improve primary care services in developing
      countries. The growing use of the electronic health record (EHR) has the
      potential of making the evaluation more efficient. The objectives of this study
      were: (a) to develop quality indicators for ANC and (b) to evaluate the quality
      of ANC using EHR information in family medicine clinics (FMCs) of Mexico City.
      METHODS: We used a mixed methods approach including: (a) in-depth interviews with
      health professionals; (b) development of indicators following the RAND-UCLA
      method; (c) a retrospective cohort study of quality of care provided to 5342
      women aged 12-49 years who had completed their pregnancy in 2009 and attended to
      at least one ANC visit with their family doctor. The study took place in four
      FMCs located in Mexico City. The source of information was the EHR. SAS
      statistical package served for programing and performing the descriptive
      statistical analysis. RESULTS: 14 ANC quality indicators were developed. The
      evaluation showed that 40.6% of women began ANC in the first trimester; 63.5%
      with low-risk pregnancy attended four or more ANC visits; 4.4% were referred for
      routine obstetric ultrasound, and 41.1% with vaginal infection were prescribed
      metronidazole. On average, the percentage of recommended care that women received
      was 32.7%. CONCLUSIONS: It is feasible to develop quality indicators suitable for
      evaluating the quality of ANC using routine EHR data. The study identified the
      ANC areas that require improvement; which can guide future strategies aimed at
      improving ANC quality.

PMID- 24885104
TI  - Delivery of health care at the end of life in cancer patients of four swiss
      cantons: a retrospective database study (SAKK 89/09).
AB  - BACKGROUND: The use of cancer related therapy in cancer patients at the end-of
      life has increased over time in many countries. Given a lack of published Swiss
      data, the objective of this study was to describe delivery of health care during
      the last month before death of cancer patients. METHODS: Claims data were used to
      assess health care utilization of cancer patients (identified by cancer registry
      data of four participating cantons), deceased between 2006-2008. Primary
      endpoints were hospitalization rate and delivery of cancer related therapies
      during the last 30 days before death. Multivariate logistic regression assessed
      the explanatory value of patient and geographic characteristics. RESULTS: 3809
      identified cancer patients were included. Hospitalization rate (mean 68.5%, 95%
      CI 67.0-69.9) and percentage of patients receiving anti-cancer drug therapies
      (ACDT, mean 14.5%, 95% CI 13.4-15.6) and radiotherapy (mean 7.7%, 95% CI 6.7-8.4)
      decreased with age. Canton of residence and insurance type status most
      significantly influenced the odds for hospitalization or receiving ACDT.
      CONCLUSIONS: The intensity of cancer specific care showed substantial variation
      by age, cancer type, place of residence and insurance type status. This may be
      partially driven by cultural differences within Switzerland and the cantonal
      organization of the Swiss health care system.

PMID- 24885105
TI  - Waterborne parasites: a current status from the Philippines.
AB  - BACKGROUND: Despite the amount of awareness created, waterborne disease still
      poses threat, especially in developing countries. Due to the scarcity of reported
      data on waterborne parasites, the consumption of unsafe water prolongs. Thus, the
      occurrences of waterborne parasites from various samples were investigated from
      one of the Southeast Asian country, the Philippines. METHODS: A total of thirty
      three samples, each consisting of twelve liters, were collected and processed to
      obtain the sediment. Ten liters of sample each was processed to detect
      Cryptosporidium spp. and Giardia spp. using an immunomagnetic separation method
      prior to enumeration via fluorescence microscope. Meanwhile, the remaining two
      liters were cultured to detect Acanthamoeba and Naegleria through microscopy
      examination and polymerase chain reaction (PCR) analysis. RESULTS: Twelve samples
      (36.4%) from river (5), swimming pool (1), pond (3), rain tank (1), and natural
      lake (2) were positive for Cryptosporidium spp., 17 (45.5%) samples from river
      (9), pond (2), swimming pool (1), rain tank (1), and natural lake (4) were
      positive for Giardia spp. while, 13 (33.3%) samples from river (3), swimming pool
      (2), pond (2), dispenser (1), well (1), tap (2) and natural lake (2) were
      positive for Acanthamoeba spp. and 5 (18.2%) samples from river (1), natural lake
      (1), tap (1), dispenser (1) and mineral (1) were Naegleria spp. positive.
      Physical parameters such as temperature, conductivity, total dissolved solid
      (TDS), salinity, dissolved oxygen (DO), pH, and turbidity and chemical parameters
      such as ammonia, chlorine, fluoride, nitrate and nitrite were also measured. The
      highest chemical contamination was observed at pond 2. A good correlation was
      observed between Giardia and nitrite (r = 0.736, p < 0.01) and Giardia and
      nitrate (r = 0.502, p < 0.01). CONCLUSION: This study was aimed to create greater
      awareness of parasitic contamination in the water environment in the Philippines
      and also to act as a platform of the current scenario for policymakers as water
      pollution is a key health issue in this region.

PMID- 24885106
TI  - The dirigent multigene family in Isatis indigotica: gene discovery and
      differential transcript abundance.
AB  - BACKGROUND: Isatis indigotica Fort. is one of the most commonly used traditional
      Chinese medicines. Its antiviral compound is a kind of lignan, which is formed
      with the action of dirigent proteins (DIR). DIR proteins are members of a large
      family of proteins which impart stereoselectivity on the phenoxy radical-coupling
      reaction, yielding optically active lignans from two molecules of E-coniferyl
      alcohol. They exist in almost every vascular plant. However, the DIR and DIR-like
      protein gene family in I. indigotica has not been analyzed in detail yet. This
      study focuses on discovery and analysis of this protein gene family in I.
      indigotica for the first time. RESULTS: Analysis of transcription profiling
      database from I. indigotica revealed a family of 19 full-length unique DIR and
      DIR-like proteins. Sequence analysis found that I. indigotica DIR and DIR-like
      proteins (IiDIR) were all-beta strand proteins, with a signal peptide at the N
      terminus. Phylogenetic analysis of the 19 proteins indicated that the IiDIR genes
      cluster into three distinct subfamilies, DIR-a, DIR-b/d, and DIR-e, of a larger
      plant DIR and DIR-like gene family. Gene-specific primers were designed for 19
      unique IiDIRs and were used to evaluate patterns of constitutive expression in
      different organs. It showed that most IiDIR genes were expressed comparatively
      higher in roots and flowers than stems and leaves. CONCLUSIONS: New DIR and DIR
      like proteins were discovered from the transcription profiling database of I.
      indigotica through bioinformatics methods for the first time. Sequence
      characteristics and transcript abundance of these new genes were analyzed. This
      study will provide basic data necessary for further studies.

PMID- 24885107
TI  - Patterns of malaria indices across three consecutive seasons in children in a
      highly endemic area of West Africa: a three times-repeated cross-sectional study.
AB  - OBJECTIVES: To study the manifestations of Plasmodium infection, and its
      relations with the malaria disease, especially when comparing dry and rainy
      seasons in a hyperendemic area of West Africa. METHODS: The study was carried out
      in an area where malaria transmission is high, showing important seasonal
      variations. One thousand children, representing the total child population (1-12
      year old), were observed transversally at the end of three consecutive seasons
      (dry/rainy/dry). The usual indicators, such as parasite density, splenomegaly,
      anaemia, or febrile disease were recorded and analysed. RESULTS: The prevalence
      of Plasmodium falciparum was high in all age groups and seasons, constantly
      around 60%. The high transmission season (rainy) showed higher rates of anaemia
      and spleen enlargement and, in the youngest children only, higher parasite
      densities. There were also differences between the two dry seasons: in the first
      one, there was a higher rate of fever than in the second one (p < 0.001). Low
      parasite density (<2,000 p/MUl) was never associated with fever during any
      season, raising some concern with regard to the usefulness of parasite detection.
      The possible origins of fever are discussed, together with the potential
      usefulness of analyzing these indices on a population sample, at a time when
      fever incidence rises and malaria is one potential cause among others. The
      distinction to be made between the Plasmodium infection and the malaria disease
      is highlighted. CONCLUSIONS: These data confirm previous hypotheses of a strong
      difference in malaria infection and disease between dry and rainy seasons. The
      most relevant seasonal indicator was not mainly parasite rate and density but
      anaemia, spleen enlargement, prevalence and possible origin of fever.
      RECOMMENDATIONS: In any situation (i.e. fever or not) and especially during the
      dry season, one must consider that detection of parasites in the blood is only
      evidence of a Plasmodium infection and not necessarily of a malaria disease. In
      such a situation, it seems suitable to obtain, through national malaria teams, a
      well-defined situation of transmission and prevalence of Plasmodium infection
      following zones and seasons, in order to adapt control strategies. For
      researchers, a systematic management of data separately for dry and rainy season
      appears mandatory.

PMID- 24885108
TI  - Detecting the neuropathic pain component in the clinical setting: a study
      protocol for validation of screening instruments for the presence of a
      neuropathic pain component.
AB  - BACKGROUND: The presence of nerve damage plays a key role in the development and
      prognosis of chronic pain states. Assessment of the presence and severity of a
      neuropathic pain component (NePC) is key in diagnosing chronic pain patients. Low
      back pain (LBP) and neck and shoulder pain (NSP) are highly prevalent and
      clinically important medical and societal problems in which a NePC is frequently
      present. The more severe the NePC, the worse the course of the pain, its
      prognosis and the results of treatment. Reliable and standardised diagnosis of
      the NePC remains difficult to achieve. Standardized and validated screening tools
      may help to reliably identify the NePC in individual chronic pain patients. The
      aim of this study is to validate the Dutch language versions of the PainDETECT
      Questionnaire (PDQ-Dlv) and the 'Douleur Neuropathique 4 Questions' (DN4-Dlv) for
      use in primary and specialist medical care settings to screen for a NePC in
      patients with chronic pain due to (1) LBP, (2) NSP or (3) known peripheral nerve
      damage (PND). METHODS/DESIGN: The study design is cross-sectional to assess the
      validity of the PDQ-Dlv and the DN4-Dlv with 2 weeks follow-up for test-retest
      reliability and 3 months follow-up for monitoring and prognosis. 438 patients
      with chronic pain due to (1) LBP, (2) NSP or (3) PND. will be included in this
      study. Based on the IASP definition of neuropathic pain, two physicians will
      independently assess whether the patient has a NEPC or not. This result will be
      compared with the outcome of the PDQ-Dlv & DN4-Dlv, the grading system for
      neuropathic pain, bed side examination and quantitative sensory testing. This
      study will further collect data regarding prevalence of NePC, general health
      status, mental health status, functioning, pain attribution and quality of life.
      DISCUSSION: The rationale for this study is to provide detailed information on
      the clinimetric quality of the PDQ-Dlv and DN4-Dlv in Dutch speaking countries.
      Our innovative multi-factorial approach should help achieve more reliable
      diagnosis and quantification of a NePC in patients with chronic pain. TRIAL
      REGISTRATION: The Netherlands National Trial Register (NTR3030).

PMID- 24885109
TI  - Outcome of bone defect reconstruction with clavicle bone cement prosthesis after
      tumor resection: a case series study.
AB  - BACKGROUND: To investigate the short and medium term outcomes of bone defect
      reconstruction with bone cement prosthesis after clavicle malignancies resection.
      METHODS: A total of 5 clavicular malignancy patients experienced bone cement
      prosthesis reconstruction after subtotal claviculectomy were enrolled the study
      from January 2005 to May 2012. Musculoskeletal Tumor Society score (MSTS), Visual
      Analogue scale (VAS) and American Shoulder and Elbow Surgeons shoulder outcome
      score (ASES) were adopted for assessment. RESULTS: The mean follow-up period was
      25.8 months. All patients were performed bone cement defect reconstruction after
      claviculectomy. In which, 3 cases showed disease-free and other 2 cases were
      alive with sickness. The average Musculoskeletal Tumor Society score was 85.40%
      +/- 5.68%(77%-90%), Visual Analogue Scale was 1.40 +/- 0.55 (1-2) and American
      Shoulder and Elbow Surgeons Shoulder Outcome Score was 92.40 +/- 3.29(87-96).
      CONCLUSIONS: Adoption of clavicle bone cement prosthesis for bone defect
      reconstruction after tumor resection can maintain the contour of shoulder and
      reduce the complications ascribe to the claviculectomy. It is an effective and
      feasible therapeutic procedure in clinical setting.

PMID- 24885111
TI  - Do emotional stimuli interfere with two distinct components of inhibition?
AB  - Emotions have recently been shown to interfere with the efficacy of inhibitory
      control. However, understanding their impact requires taking into account that
      inhibition is not a unitary construct, but consists of distinct functions
      underlain by specific mechanisms. In this study, 88 participants performed two
      emotional versions of classic laboratory tasks designed to assess (1) the ability
      to inhibit a prepotent response (a stop-signal task using faces with different
      emotional expressions) and (2) the capacity to resist the effect of proactive
      interference (PI; a recent negative task that included emotional words). Overall
      results showed that emotional stimuli interfered with inhibition capacities in
      both tasks. Although tending in the same direction, these results suggest that
      different underlying mechanisms (e.g., top-down vs. bottom-up processes) or
      consecutive differences in emotional processing (e.g., different interactions
      with stimulus/task properties, processing stages or motivational aspects) are at
      play in these two inhibition-related functions. 

PMID- 24885110
TI  - Prospective signs of cleidocranial dysplasia in Cebpb deficiency.
AB  - BACKGROUND: Although runt-related transcription factor 2 (RUNX2) has been
      considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were
      free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (Cebpb) is a key
      factor of Runx2 expression and our previous study has reported two CCD signs
      including hyperdontia and elongated coronoid process of the mandible in Cebpb
      deficient mice. Following that, this work aimed to conduct a case-control study
      of thoracic, zygomatic and masticatory muscular morphology to propose an
      association between musculoskeletal phenotypes and deficiency of Cebpb, using a
      sample of Cebpb-/-, Cebpb+/- and Cebpb+/+ adult mice. Somatic skeletons and
      skulls of mice were inspected with soft x-rays and micro-computed tomography
      (MUCT), respectively. Zygomatic inclination was assessed using methods of
      coordinate geometry and trigonometric function on anatomic landmarks identified
      with MUCT. Masseter and temporal muscles were collected and weighed. Expression
      of Cebpb was examined with a reverse transcriptase polymerase chain reaction (RT
      PCR) technique. RESULTS: Cebpb-/- mice displayed hypoplastic clavicles, a narrow
      thoracic cage, and a downward tilted zygomatic arch (p < 0.001). Although Cebpb+/
      mice did not show the phenotypes above (p = 0.357), a larger mass percentage of
      temporal muscles over masseter muscles was seen in Cebpb+/- littermates (p =
      0.012). The mRNA expression of Cebpb was detected in the clavicle, the zygoma,
      the temporal muscle and the masseter muscle, respectively. CONCLUSIONS:
      Prospective signs of CCD were identified in mice with Cebpb deficiency. These
      could provide an additional aetiological factor of CCD. Succeeding investigation
      into interactions among Cebpb, Runx2 and musculoskeletal development is
      indicated.

PMID- 24885113
TI  - How likely is "likely to reoffend" in sex offender civil commitment trials?
AB  - Many sexually violent predator (SVP) laws are ambiguous regarding the degree of
      reoffense risk that would indicate that an offender is sufficiently "likely to
      reoffend" to justify civil commitment. We review how SVP statutes operationalize
      likelihood of reoffending. We then examine what likelihood of recidivism actual
      SVP jurors considered to indicate that an offender was likely to reoffend. Real
      jurors (N = 153) from 14 actual SVP hearings completed a questionnaire after
      deliberating to a verdict. Most jurors (81.7%) considered a 15% estimated chance
      of recidivism to mean that the respondent was "likely" to reoffend, and many
      (53.6%) even considered a 1% chance to indicate likely reoffense. Jurors who
      heard lower risk estimates in trials were more likely to report that a low chance
      of recidivism (as low as 1%) indicated an offender was likely to reoffend.
      Results suggest that jurors view risk more in terms of the severity of potential
      harm than in terms of strict statistical probability. Results also suggest that
      when laws give jurors discretion to define tolerable risk, jurors consider even a
      statistically low degree of risk intolerable.

PMID- 24885112
TI  - Correlating tumor metabolic progression index measured by serial FDG PET-CT,
      apparent diffusion coefficient measured by magnetic resonance imaging (MRI) and
      blood genomics to patient's outcome in advanced colorectal cancer: the CORIOLAN
      study.
AB  - BACKGROUND: Metastatic colorectal cancer (mCRC) may present various behaviours
      that define different courses of tumor evolution. There is presently no available
      tool designed to assess tumor aggressiveness, despite the fact that this is
      considered to have a major impact on patient outcome. METHODS/DESIGN: CORIOLAN is
      a single-arm prospective interventional non-therapeutic study aiming mainly to
      assess the natural tumor metabolic progression index (TMPI) measured by serial
      FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for
      overall survival (OS) in patients with mCRC.Secondary objectives of the study aim
      to test the TMPI as a prognostic marker for progression-free survival (PFS), to
      assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to
      compare TMPI to classical clinico-biological assessment of prognosis, and to test
      the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient
      (ADC) and variation of vADC using voxel-based diffusion maps.Additionally, this
      study intends to identify genomic and epigenetic factors that correlate with
      progression of tumors and the OS of patients with mCRC. Consequently, this
      analysis will provide information about the signaling pathways that determine the
      natural and therapy-free course of the disease. Finally, it would be of great
      interest to investigate whether in a population of patients with mCRC, for which
      at present no known effective therapy is available, tumor aggressiveness is
      related to elevated levels of circulating tumor cells (CTCs) and to patient
      outcome. DISCUSSION: Tumor aggressiveness is one of the major determinants of
      patient outcome in advanced disease. Despite its importance, supported by
      findings reported in the literature of extreme outcomes for patients with mCRC
      treated with chemotherapy, no objective tool allows clinicians to base treatment
      decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET
      based metabolic imaging of patients with chemorefractory mCRC during a period of
      time without treatment. Results will be correlated to other assessment tools like
      DW-MRI, CTCs and circulating DNA, with the aim to provide usable tools in daily
      practice and in clinical studies in the future. ClinicalTrials.gov Number:
      NCT01591590.

PMID- 24885114
TI  - Do we need a different organ allocation system for kidney transplants using
      donors after circulatory death?
AB  - BACKGROUND: There is no national policy for allocation of kidneys from Donation
      after circulatory death (DCD) donors in the UK. Allocation is geographical and
      based on individual/regional centre policies. We have evaluated the short term
      outcomes of paired kidneys from DCD donors subject to this allocation policy.
      METHODS: Retrospective analysis of paired renal transplants from DCD's from 2002
      to 2010 in London. Cold ischemia time (CIT), recipient risk factors, delayed
      graft function (DGF), 3 and 12 month creatinine) were compared. RESULTS: Complete
      data was available on 129 paired kidneys.115 pairs were transplanted in the same
      centre and 14 pairs transplanted in different centres. There was a significant
      increase in CIT in kidneys transplanted second when both kidneys were accepted by
      the same centre (15.5 +/- 4.1 vs 20.5 +/- 5.8 hrs p<0.0001 and at different
      centres (15.8 +/- 5.3 vs. 25.2 +/- 5.5 hrs p=0.0008). DGF rates were increased in
      the second implant following sequential transplantation (p=0.05). CONCLUSIONS:
      Paired study sequential transplantation of kidneys from DCD donors results in a
      significant increase in CIT for the second kidney, with an increased risk of DGF.
      Sequential transplantation from a DCD donor should be avoided either by the
      availability of resources to undertake simultaneous procedures or the allocation
      of kidneys to 2 separate centres.

PMID- 24885115
TI  - Assessment of functional impairment after knee anterior cruciate ligament
      reconstruction using cardiorespiratory parameters: a cross-sectional study.
AB  - BACKGROUND: A dynamic sub-maximum exercise with the same absolute intensity,
      performed with different muscle groups, may present exacerbated cardiorespiratory
      responses. Therefore, cardiorespiratory responses to unilateral exercise may
      identify bilateral differences. The purpose of this study was to verify whether
      the cardiorespiratory responses to lower limb exercise display counter-lateral
      differences, and if they could be used to assist athletes and health
      professionals involved in rehabilitation. METHODS: Nine individuals participated
      in this cross-sectional study. They had been treated in a private rehabilitation
      clinic and submitted to intra-articular reconstruction of the anterior cruciate
      ligament. The cycling exercise with the same sub-maximal intensity and with one
      lower limb was used to gather data. Cardiorespiratory responses to exercise were
      compared between exercises performed with the involved and uninvolved limb after
      five minutes of exercise. RESULTS: Cardiorespiratory responses to exercise
      performed with the involved limb presented higher values after five minutes of
      cycling: oxygen uptake (+7%), carbon dioxide production (+10%), minute
      ventilation (+20%), breathing frequency (+19%), ventilatory equivalent for oxygen
      (+14%), end-tidal pressure of O2 oxygen (+4%), end-tidal pressure of O2 carbon
      dioxide (-9%) and heart rate (+9%). CONCLUSIONS: The exacerbated responses,
      including increase of the ventilatory equivalent and decrease of end-tidal
      pressure of carbon dioxide, indicate that this exercise protocol may be useful in
      the characterization of the functional deficit of the surgical limb during
      rehabilitation.

PMID- 24885116
TI  - CD40 mutant expression and its clinical significance to prognosis in gastric
      cancer patients.
AB  - BACKGROUND: We aimed to detect CD40 mutant expression and evaluate its clinical
      significance in gastric cancer. METHODS: CD40 mutant expression in 78 cases of
      gastric cancer tissues, 10 cases of normal gastric tissues, and 10 cases of
      gastric adenoma tissues by immunohistochemical test. Survival analyses were also
      performed. RESULTS: The positive CD40 mutant rate in gastric cancer was 55.1%
      (43/78). No positive CD40 mutant staining was observed in the normal gastric
      tissue or the gastric adenoma. CD40 mutants expression was significantly
      correlated with invasive depth, lymph metastasis, and TNM stage (P <0.05). Cases
      with negative CD40 mutant expression had a significantly longer median survival
      time than those with positive CD40 mutant expression (40 vs. 14 months, P <0.05).
      A lower death risk in negative CD40 mutant cases was observed comparing with
      positive CD40 mutant cases. CONCLUSIONS: Positive CD40 mutant expression suggests
      a poorer prognosis of gastric cancer cases.

PMID- 24885117
TI  - Characteristics and determinants of endurance cycle ergometry and six-minute walk
      distance in patients with COPD.
AB  - BACKGROUND: Exercise tolerance can be assessed by the cycle endurance test (CET)
      and six-minute walk test (6MWT) in patients with Chronic Obstructive Pulmonary
      Disease (COPD). We sought to investigate the characteristics of functional
      exercise performance and determinants of the CET and 6MWT in a large clinical
      cohort of COPD patients. METHODS: A dataset of 2053 COPD patients (43% female,
      age: 66.9 +/- 9.5 years, FEV1% predicted: 48.2 +/- 23.2) was analyzed
      retrospectively. Patients underwent, amongst others, respiratory function
      evaluation; medical tests and questionnaires, one maximal incremental cycle test
      where peak work rate was determined and two functional exercise tests: a CET at
      75% of peak work rate and 6MWT. A stepwise multiple linear regression was used to
      assess determinants. RESULTS: On average, patients had impaired exercise
      tolerance (peak work rate: 56 +/- 27% predicted, 6MWT: 69 +/- 17% predicted). A
      total of 2002 patients had CET time of duration (CET-Tend) less than 20 min while
      only 51 (2.5%) of the patients achieved 20 min of CET-Tend . In former patients,
      the percent of predicted peak work rate achieved differed significantly between
      men (48 +/- 21% predicted) and women (67 +/- 31% predicted). In contrast, CET
      Tend was longer in men (286 +/- 174 s vs 250 +/- 153 s, p < 0.001). Also, six
      minute walking distance (6MWD) was higher in men compared to women, both in
      absolute terms as in percent of predicted (443 m, 67%predicted vs 431 m,
      72%predicted, p < 0.05). Gender was associated with the CET-Tend but BMI, FEV1
      and FRC were related to the 6MWD highlighting the different determinants of
      exercise performance between CET and 6MWT. CONCLUSIONS: CET-Tend is a valuable
      outcome of CET as it is related to multiple clinical aspects of disease severity
      in COPD. Gender difference should temper the interpretation of CET.

PMID- 24885119
TI  - Immobilization of semisoft colloidal crystals formed by polymer-brush-afforded
      hybrid particles.
AB  - An immobilization technique for semisoft colloidal crystals, which are ordered
      arrays of polymer-brush-afforded hybrid particles synthesized by surface
      initiated living radical polymerization (SI-LRP), is reported. Silica particles
      were first grafted with well-defined block copolymers of poly(methyl methacrylate
      co-hydroxyethyl methacrylate)-b-poly(methyl methacrylate), P(MMA-co-HEMA)-b-PMMA
      by SI-LRP, which gave a graft density as high as 0.7 chains/nm(2). The HEMA units
      reacted with 2-isocyanatoethyl methacrylate to introduce vinyl groups at the
      outer layer of the polymer-brush shell. The modified hybrid particles formed a
      colloidal crystal in a solution containing a small amount of free polymers with
      vinyl groups. The colloidal crystal was photoirradiated in the presence of a
      photoradical initiator to immobilize it through a cross-linking reaction among
      the vinyl groups. The structural analyses of the colloidal crystals before and
      after the photoirradiation were carried out by confocal laser scanning
      microscopy; the results showed that the periodic structures of the crystals were
      maintained after immobilization. 

PMID- 24885118
TI  - Temporal evolution in caveolin 1 methylation levels during human esophageal
      carcinogenesis.
AB  - BACKGROUND: Esophageal cancer ranks eighth among frequent cancers worldwide. Our
      aim was to investigate whether and at which neoplastic stage promoter
      hypermethylation of CAV1 is involved in human esophageal carcinogenesis. METHODS:
      Using real-time quantitative methylation-specific PCR (qMSP), we examined CAV1
      promoter hypermethylation in 260 human esophageal tissue specimens. Real-time RT
      PCR and qMSP were also performed on OE33 esophageal cancer cells before and after
      treatment with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC).
      RESULTS: CAV1 hypermethylation showed highly discriminative ROC curve profiles,
      clearly distinguishing esophageal adenocarcinomas (EAC) and esophageal squamous
      cell carcinomas (ESCC) from normal esophagus (NE) (EAC vs. NE, AUROC = 0.839 and
      p < 0.0001; ESCC vs. NE, AUROC = 0.920 and p < 0.0001). Both CAV1 methylation
      frequency and normalized methylation value (NMV) were significantly higher in
      Barrett's metaplasia (BE), low-grade and high-grade dysplasia occurring in BE
      (D), EAC, and ESCC than in NE (all p < 0.01, respectively). Meanwhile, among 41
      cases with matched NE and EAC or ESCC, CAV1 NMVs in EAC and ESCC (mean = 0.273)
      were significantly higher than in corresponding NE (mean = 0.146; p < 0.01,
      Student's paired t-test). Treatment of OE33 EAC cells with 5-Aza-dC reduced CAV1
      methylation and increased CAV1 mRNA expression. CONCLUSIONS: CAV1 promoter
      hypermethylation is a frequent event in human esophageal carcinomas and is
      associated with early neoplastic progression in Barrett's esophagus.

PMID- 24885120
TI  - Transcriptomic analyses reveal the adaptive features and biological differences
      of guts from two invasive whitefly species.
AB  - BACKGROUND: The gut of phloem feeding insects is critical for nutrition uptake
      and xenobiotics degradation. However, partly due to its tiny size, genomic
      information for the gut of phloem feeding insects is limited. RESULTS: In this
      study, the gut transcriptomes of two species of invasive whiteflies in the
      Bemisia tabaci complex, Middle East Asia Minor 1 (MEAM1) and Mediterranean (MED),
      were analyzed using the Illumina sequencing. A total of 12,879 MEAM1 transcripts
      and 11,246 MED transcripts were annotated with a significant Blastx hit. In
      addition, 7,000 and 5,771 gut specific genes were respectively identified for
      MEAM1 and MED. Functional analyses on these gut specific genes demonstrated the
      important roles of gut in metabolism of insecticides and secondary plant
      chemicals. To reveal the molecular difference between guts of MEAM1 and MED, a
      comparison between gut transcriptomes of the two species was conducted and 3,910
      pairs of orthologous genes were identified. Based on the ratio of nonsynonymous
      and synonymous substitutions, 15 genes were found evolving under positive
      selection. Many of those genes are predicted to be involved in metabolism and
      insecticide resistance. Furthermore, many genes related to detoxification were
      expressed at an elevated level in the gut of MED compared to MEAM1, which might
      be responsible for the MED's higher resistance to insecticides and environmental
      stresses. CONCLUSION: The sequencing of MED and MEAM1 gut transcriptomes and
      extensive comparisons of MEAM1 and MED gut transcripts provide substantial
      sequence information for revealing the role of gut in whiteflies.

PMID- 24885121
TI  - Oral immunization with recombinant enterovirus 71 VP1 formulated with chitosan
      protects mice against lethal challenge.
AB  - BACKGROUND: Enterovirus 71 (EV71) is the etiologic agent of hand-foot-and-mouth
      disease (HFMD) in the Asia-Pacific region, Many strategies have been applied to
      develop EV71 vaccines but no vaccines are currently available. Mucosal
      immunization of the VP1, a major immunogenic capsid protein of EV71, may be an
      alternative way to prevent EV71 infection. RESULTS: In this study, mucosal
      immunogenicity and protect function of recombinant VP1 protein (rVP1) in
      formulation with chitosan were tested and assessed in female ICR mouse model. The
      results showed that the oral immunization with rVP1 induced VP1-specific IgA
      antibodies in intestine, feces, vagina, and the respiratory tract and serum
      specific IgG and neutralization antibodies in vaccinated mice. Splenocytes from
      rVP1-immunized mice induced high levels of Th1 (cytokine IFN-gamma), Th2
      (cytokine IL-4) and Th3 (cytokine TGF-beta) type immune responses after
      stimulation. Moreover, rVP1-immunized mother mice conferred protection (survival
      rate up to 30%) on neonatal mice against a lethal challenge of 103 plaque-forming
      units (PFU) EV71. CONCLUSIONS: These data indicated that oral immunization with
      rVP1 in formulation with chitosan was effective in inducing broad-spectrum immune
      responses and might be a promising subunit vaccine candidate for preventing EV71
      infection.

PMID- 24885122
TI  - Azithromycin is able to control Toxoplasma gondii infection in human villous
      explants.
AB  - BACKGROUND: Although Toxoplasma gondii infection is normally asymptomatic, severe
      cases of toxoplasmosis may occur in immunosuppressed patients or congenitally
      infected newborns. When a fetal infection is established, the recommended
      treatment is a combination of pyrimethamine, sulfadiazine and folinic acid (PSA).
      The aim of the present study was to evaluate the efficacy of azithromycin to
      control T. gondii infection in human villous explants. METHODS: Cultures of third
      trimester human villous explants were infected with T. gondii and simultaneously
      treated with either PSA or azithromycin. Proliferation of T. gondii, as well as
      production of cytokines and hormones by chorionic villous explants, was analyzed.
      RESULTS: Treatment with either azithromycin or PSA was able to control T. gondii
      infection in villous explants. After azithromycin or PSA treatment, TNF-alpha, IL
      17A or TGF-beta1 levels secreted by infected villous explants did not present
      significant differences. However, PSA-treated villous explants had decreased
      levels of IL-10 and increased IL-12 levels, while treatment with azithromycin
      increased production of IL-6. Additionally, T. gondii-infected villous explants
      increased secretion of estradiol, progesterone and HCG+beta, while treatments
      with azithromycin or PSA reduced secretion of these hormones concurrently with
      decrease of parasite load. CONCLUSIONS: In conclusion, these results suggest that
      azithromycin may be defined as an effective alternative drug to control T. gondii
      infection at the fetal-maternal interface.

PMID- 24885123
TI  - Cross cultural adaptation and validation of a Spanish version of the Lower Limb
      Functional Index.
AB  - BACKGROUND: The Lower Limb Functional Index (LLFI) is a relatively recently
      published regional outcome measure. The development article showed the LLFI had
      robust and valid clinimetric properties with sound psychometric and practical
      characteristics when compared to the Lower Limb Extremity Scale (LEFS) criterion
      standard. OBJECTIVE: The purpose of this study was cross cultural adaptation and
      validation of the LLFI Spanish-version (LLFI-Sp) in a Spanish population.
      METHODS: A two stage observational study was conducted. The LLFI was initially
      cross-culturally adapted to Spanish through double forward and single backward
      translation; then subsequently validated for the psychometric characteristics of
      validity, internal consistency, reliability, error score and factor structure.
      Participants (n = 136) with various lower limb conditions of >12 weeks duration
      completed the LLFI-Sp, Western Ontario and McMaster University Osteoarthritis
      Index (WOMAC) and the Euroqol Health Questionnaire 5 Dimensions (EQ-5D-3 L). The
      full sample was employed to determine internal consistency, concurrent criterion
      validity, construct validity and factor structure; a subgroup (n = 45) determined
      reliability at seven days concurrently completing a global rating of change
      scale. RESULTS: The LLFI-Sp demonstrated high but not excessive internal
      consistency (alpha = 0.91) and high reliability (ICC = 0.96). The factor
      structure was one-dimensional which supported the construct validity. Criterion
      validity with the WOMAC was strong (r = 0.77) and with the EQ-5D-3 L fair and
      inversely correlated (r = -0.62). The study limitations included the lack of
      longitudinal data and the determination of responsiveness. CONCLUSIONS: The LLFI
      Sp supports the findings of the original English version as being a valid lower
      limb regional outcome measure. It demonstrated similar psychometric properties
      for internal consistency, validity, reliability, error score and factor
      structure.

PMID- 24885124
TI  - Automated FiO2-SpO2 control system in neonates requiring respiratory support: a
      comparison of a standard to a narrow SpO2 control range.
AB  - BACKGROUND: Managing the oxygen saturation of preterm infants to a target range
      has been the standard of care for a decade. Changes in target ranges have been
      shown to significantly impact mortality and morbidity. Selecting and implementing
      the optimal target range are complicated not only by issues of training, but also
      the realities of staffing levels and demands. The potential for automatic control
      is becoming a reality. Results from the evaluation of different systems have been
      promising and our own experience encouraging. METHODS: This study was conducted
      in two tertiary level newborn nurseries, routinely using an automated FiO2-SpO2
      control system (Avea-CLiO2, Yorba Linda CA, USA). The aim of this study was to
      compare the performance of the system as used routinely (set control range of 87
      93% SpO2), to a narrower higher range (90-93%). We employed a 12-hour cross-over
      design with the order of control ranges randomly assigned for each of up to three
      days. The primary prospectively identified end points were time in the 87-93%
      SpO2 target range, time at SpO2 extremes and the distribution of the SpO2
      exposure. RESULTS: Twenty-one infants completed the study. The infants were born
      with a median EGA of 27 weeks and studied at a median age of 17 days and weight
      of 1.08 kg. Their median FiO2 was 0.32; 8 were intubated, and the rest
      noninvasively supported (7 positive pressure ventilation and 6 CPAP). The control
      in both arms was excellent, and required less than 2 manual FiO2 adjustments per
      day. There were no differences in the three primary endpoints. The
      narrower/higher set control range resulted in tighter control (IQR 3.0 vs. 4.3 p
      < 0.001), and less time with the SpO2 between 80-86 (6.2% vs. 8.4%, p = 0.006).
      CONCLUSIONS: We found that a shift in the median of the set control range of an
      automated FiO2-SpO2 control system had a proportional effect on the median and
      distribution of SpO2 exposure. We found that a dramatic narrowing of the set
      control range had a disproportionally smaller impact. Our study points to the
      potential to optimize SpO2 targeting with an automated control system.

PMID- 24885125
TI  - Is it time to shift the attention on early stages embryo development to avoid
      inconclusive evidence on HPV-related infertility: debate and proposal.
AB  - BACKGROUND: Current evidence about in-vivo effects of HPV cannot definitively
      clarify the possible negative role of this worldwide common infection in early
      embryo development. However in-vitro evidence, seems to underline a possible
      negative effect of HPV in increasing blastocyst apoptosis and in reducing the
      endometrial implantation of trophoblastic cells. On these bases we believe that a
      new scientific approach is necessary to better understand the real role of male
      and female HPV infection in infertility and early pregnancy development. METHODS:
      English literature review of manuscripts focused on HPV infection and human
      reproduction was conducted. We performed a critical analysis of evidence and
      possible bias affecting both in-vivo and in-vitro studies regarding this topic.
      RESULTS: The biggest limitation of the in-vivo studies is due to the
      inappropriate timing of HPV effects evaluation since evidence about in-vitro
      studies strongly suggests that a large part of HPV negative effects occurs during
      a very early stage of embryo development. All the efforts of the scientific
      community to investigate the real role of HPV in human reproduction disorders
      cannot underestimate the severe BIAS of actual evidence in postulating new
      hypothesis and research projects which are fundamental to clarify if HPV may be
      associated with unexplained couples infertility and early miscarriages.
      CONCLUSIONS: If the relationship between HPV gametes infection and early human
      reproduction step impairment will be confirmed, the HPV male and couple
      vaccination may represent a reliable option to improve fertility in some couples
      affected by infertility actually classified as "idiopathic" but maybe linked to
      HPV infection.

PMID- 24885126
TI  - Whole exome sequencing reveals concomitant mutations of multiple FA genes in
      individual Fanconi anemia patients.
AB  - BACKGROUND: Fanconi anemia (FA) is a rare inherited genetic syndrome with highly
      variable clinical manifestations. Fifteen genetic subtypes of FA have been
      identified. Traditional complementation tests for grouping studies have been used
      generally in FA patients and in stepwise methods to identify the FA type, which
      can result in incomplete genetic information from FA patients. METHODS: We
      diagnosed five pediatric patients with FA based on clinical manifestations, and
      we performed exome sequencing of peripheral blood specimens from these patients
      and their family members. The related sequencing data were then analyzed by
      bioinformatics, and the FANC gene mutations identified by exome sequencing were
      confirmed by PCR re-sequencing. RESULTS: Homozygous and compound heterozygous
      mutations of FANC genes were identified in all of the patients. The FA subtypes
      of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients
      harbored multiple mutations in at least two FA genes, and some of these mutations
      have not been previously reported. These patients' clinical manifestations were
      vastly different from each other, as were their treatment responses to
      androstanazol and prednisone. This finding suggests that heterozygous mutation(s)
      in FA genes could also have diverse biological and/or pathophysiological effects
      on FA patients or FA gene carriers. Interestingly, we were not able to identify
      de novo mutations in the genes implicated in DNA repair pathways when the
      sequencing data of patients were compared with those of their parents.
      CONCLUSIONS: Our results indicate that Chinese FA patients and carriers might
      have higher and more complex mutation rates in FANC genes than have been
      conventionally recognized. Testing of the fifteen FANC genes in FA patients and
      their family members should be a regular clinical practice to determine the
      optimal care for the individual patient, to counsel the family and to obtain a
      better understanding of FA pathophysiology.

PMID- 24885127
TI  - The 'placement' of people with profound impairments across the lifespan: re
      thinking age criteria.
AB  - BACKGROUND: Advances in lifesaving technologies and treatments make it possible
      for children with profound physical and cognitive impairments to survive into
      adulthood. Questions regarding how and where they should live are discussed
      rarely and, when they are, primarily focus on safety and/or containing costs.
      Since models of long-term care provision are age-based, children who reside in
      institutions are 'discharged' to adult facilities when they reach an arbitrary
      age. Such transfers may not be in the best interests of these young people or
      their families. Our aim in this debate is to highlight why age is a problematic
      criterion for placement decisions, with the goal of stimulating further research
      and inquiry. DISCUSSION: Transfers from pediatric to adult institutions are
      driven primarily by funding arrangements and underpinned by stage-based theories
      of human development. Arguments supporting such transfers point to the value of
      communal living with same age peers, and engagement in age-appropriate
      activities. These goals are questionable for individuals who are minimally
      interactive and/or where equally worthy interactions are feasible in
      intergenerational settings. Instead their accommodation needs might more closely
      align with palliative care principles of supporting individuals and families to
      enjoy what they bring to each other's lives and minimize suffering. Innovative
      models of 'vertical care' and 'lifetime homes', which enable continuous flexible
      services across the lifespan, are discussed as examples of alternative approaches
      requiring further debate and research. SUMMARY: Entrenched funding and service
      models that require the transfer of profoundly impaired young people from
      pediatric to adult facilities need to be re-examined with considerations of best
      interests, needs, and preferences of individuals and their families. Questions of
      what constitutes a 'good life' for these individuals are tenacious and require
      further thought and research. Nevertheless, they need to be regarded as citizens
      of our human community deserving of a good life in whatever form that may take,
      in settings that enable them to flourish.

PMID- 24885128
TI  - Prediction of high-risk areas for visceral leishmaniasis using socioeconomic
      indicators and remote sensing data.
AB  - Spatial heterogeneity in the incidence of visceral leishmaniasis (VL) is an
      important aspect to be considered in planning control actions for the disease.
      The objective of this study was to predict areas at high risk for visceral
      leishmaniasis (VL) based on socioeconomic indicators and remote sensing data. We
      applied classification and regression trees to develop and validate prediction
      models. Performance of the models was assessed by means of sensitivity,
      specificity and area under the ROC curve. The model developed was able to
      discriminate 15 subsets of census tracts (CT) with different probabilities of
      containing CT with high risk of VL occurrence. The model presented, respectively,
      in the validation and learning samples, sensitivity of 79% and 52%, specificity
      of 75% and 66%, and area under the ROC curve of 83% and 66%. Considering the
      complex network of factors involved in the occurrence of VL in urban areas, the
      results of this study showed that the development of a predictive model for VL
      might be feasible and useful for guiding interventions against the disease, but
      it is still a challenge as demonstrated by the unsatisfactory predictive
      performance of the model developed.

PMID- 24885129
TI  - Common risk factor approach to address socioeconomic inequality in the oral
      health of preschool children--a prospective cohort study.
AB  - BACKGROUND: Dental caries remains the most prevalent chronic condition in
      children and a major contributor to poor general health. There is ample evidence
      of a skewed distribution of oral health, with a small proportion of children in
      the population bearing the majority of the burden of the disease. This minority
      group is comprised disproportionately of socioeconomically disadvantaged
      children. An in-depth longitudinal study is needed to better understand the
      determinants of child oral health, in order to support effective evidence-based
      policies and interventions in improving child oral health. The aim of the Study
      of Mothers' and Infants' Life Events Affecting Oral Health (SMILE) project is to
      identify and evaluate the relative importance and timing of critical factors that
      shape the oral health of young children and then to seek to evaluate those
      factors in their inter-relationship with socioeconomic influences.
      METHODS/DESIGN: This investigation will apply an observational prospective study
      design to a cohort of socioeconomically-diverse South Australian newborns and
      their mothers, intensively following these dyads as the children grow to toddler
      age. Mothers of newborn children will be invited to participate in the study in
      the early post-partum period. At enrolment, data will be collected on parental
      socioeconomic status, mothers' general and dental health conditions, details of
      the pregnancy, infant feeding practice and parental health behaviours and
      practices. Data on diet and feeding practices, oral health behaviours and
      practices, and dental visiting patterns will be collected at 3, 6, 12 and 24
      months of age. When children turn 24-30 months, the children and their
      mothers/primary care givers will be invited to an oral examination to record oral
      health status. Anthropometric assessment will also be conducted. DISCUSSION: This
      prospective cohort study will examine a wide range of determinants influencing
      child oral health and related general conditions such as overweight. It will lead
      to the evaluation of the inter-relationship among main influences and their
      relative effect on child oral health. The study findings will provide high level
      evidence of pathways through which socio-environmental factors impact child oral
      health. It will also provide an opportunity to examine the relationship between
      oral health and childhood overweight.

PMID- 24885130
TI  - Determinants of distance walked during the six-minute walk test in patients
      undergoing cardiac surgery at hospital discharge.
AB  - INTRODUCTION: The aim of this study was to identify the determinants of distance
      walked in six-minute walk test (6MWD) in patients undergoing cardiac surgery at
      hospital discharge. METHODS: The assessment was performed preoperatively and at
      discharge. Data from patient records were collected and measurement of the
      Functional Independence Measure (FIM) and the Nottingham Health Profile (NHP)
      were performed. The six-minute walk test (6MWT) was performed at discharge.
      Patients undergoing elective cardiac surgery, coronary artery bypass grafting or
      valve replacement were eligible. Patients older than 75 years who presented
      arrhythmia during the protocol, with psychiatric disorders, muscular or
      neurological disorders were excluded from the study. RESULTS: Sixty patients
      (44.26% male, mean age 51.53 +/- 13 years) were assessed. In multivariate
      analysis the following variables were selected: type of surgery (P = 0.001),
      duration of cardiopulmonary bypass (CPB) (P = 0.001), Functional Independence
      Measure - FIM (0.004) and body mass index - BMI (0.007) with r = 0.91 and r2 =
      0.83 with P < 0.001. The equation derived from multivariate analysis: 6MWD =
      Surgery (89.42) + CPB (1.60) + MIF (2.79 ) - BMI (7.53) - 127.90. CONCLUSION: In
      this study, the determinants of 6MWD in patients undergoing cardiac surgery were:
      the type of surgery, CPB time, functional capacity and body mass index.

PMID- 24885131
TI  - The likelihood of khat chewing serving as a neglected and reverse 'gateway' to
      tobacco use among UK adult male khat chewers: a cross sectional study.
AB  - BACKGROUND: Chewing khat leaves is often accompanied by tobacco use. We assessed
      aspects of tobacco use and explored factors associated with tobacco use patterns
      (frequency of use per week) among khat chewers who used tobacco only when chewing
      khat ("simultaneous tobacco and khat users", STKU). METHODS: A sample of 204 male
      khat chewers was recruited during random visits to khat outlets. Data collected
      included socio-demographic items, tobacco use and khat chewing behaviours. Both
      psychological and physical dependence on khat were assessed using the Severity of
      Psychological Dependence on Khat (SDS-Khat) Scale, the Diagnostic Statistical
      Manual IV (DSM-IV) and adapted items from the Fagerstrom Test for Nicotine
      Dependence (chewing even when ill, and difficulty in abstaining from khat chewing
      for an entire week). Descriptive statistics and non-parametric analyses were
      conducted. RESULTS: Of the 204 khat chewers, 35% were khat chewers only, 20% were
      STKU, and the remainder were daily cigarette smokers. The mean age of STKU was
      38.12 (+/-14.05) years. Fifty seven percent of STKU smoked tobacco and chewed
      khat for two days per week and 43% smoked and chewed more frequently (three to
      six days: 33%, daily: 10%). Three quarters (74%) were former daily tobacco users.
      Khat chewing initiated tobacco smoking among 45% of STKU and 71% reported
      attempts to quit tobacco smoking during khat chew. Among STKU, smoking tobacco
      for more than two days per week was significantly associated (p < 0.05) with
      psychological dependence (increased levels of SDS-Khat), physical dependence
      (increased levels of DSM-IV symptoms, chewing even when ill, difficulty in
      abstaining from chewing for an entire week and self-reported health conditions)
      and behavioural factors (e.g. amount of khat chewed in typical khat session).
      CONCLUSIONS: Khat chewing may promote different patterns of tobacco smoking,
      initiate and sustain tobacco smoking, and trigger tobacco cessation relapses
      among STKU. Increased frequency of tobacco smoking among STKU was linked to
      psycho-physical and behavioural factors. Further investigation within large and
      representative samples of both sexes of STKU in different contexts should be
      considered for health research and policy development. Khat chewing should be
      considered when designing tobacco prevention uptake, cessation interventions and
      relapse prevention programmes.

PMID- 24885132
TI  - Evaluating the optimal timing of surgical antimicrobial prophylaxis: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Surgical site infections are the most common hospital-acquired
      infections among surgical patients. The administration of surgical antimicrobial
      prophylaxis reduces the risk of surgical site infections . The optimal timing of
      this procedure is still a matter of debate. While most studies suggest that it
      should be given as close to the incision time as possible, others conclude that
      this may be too late for optimal prevention of surgical site infections. A large
      observational study suggests that surgical antimicrobial prophylaxis should be
      administered 74 to 30 minutes before surgery. The aim of this article is to
      report the design and protocol of a randomized controlled trial investigating the
      optimal timing of surgical antimicrobial prophylaxis. METHODS/DESIGN: In this bi
      center randomized controlled trial conducted at two tertiary referral centers in
      Switzerland, we plan to include 5,000 patients undergoing general, oncologic,
      vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio
      into two groups: one receiving surgical antimicrobial prophylaxis in the
      anesthesia room (75 to 30 minutes before incision) and the other receiving
      surgical antimicrobial prophylaxis in the operating room (less than 30 minutes
      before incision). We expect a significantly lower rate of surgical site
      infections with surgical antimicrobial prophylaxis administered more than 30
      minutes before the scheduled incision. The primary outcome is the occurrence of
      surgical site infections during a 30-day follow-up period (one year with an
      implant in place). When assuming a 5% surgical site infection risk with
      administration of surgical antimicrobial prophylaxis in the operating room, the
      planned sample size has an 80% power to detect a relative risk reduction for
      surgical site infections of 33% when administering surgical antimicrobial
      prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We
      expect the study to be completed within three years. DISCUSSION: The results of
      this randomized controlled trial will have an important impact on current
      international guidelines for infection control strategies in the hospital.
      Moreover, the results of this randomized controlled trial are of significant
      interest for patient safety and healthcare economics. TRIAL REGISTRATION: This
      trial is registered on ClinicalTrials.gov under the identifier NCT01790529.

PMID- 24885133
TI  - Increased 3-hydroxypropionic acid production from glycerol, by modification of
      central metabolism in Escherichia coli.
AB  - BACKGROUND: 3-hydroxypropionic acid (3HP) is an important chemical precursor for
      the production of bioplastics. Microbial production of 3HP from glycerol has
      previously been developed through the optimization of culture conditions and the
      3HP biosynthesis pathway. In this study, a novel strategy for improving 3HP
      production in Escherichia coli was investigated by the modification of central
      metabolism based on a genome-scale metabolic model and experimental validation.
      RESULTS: Metabolic simulation identified the double knockout of tpiA and zwf as a
      candidate for improving 3HP production. A 3HP-producing strain was constructed by
      the expression of glycerol dehydratase and aldehyde dehydrogenase. The double
      knockout of tpiA and zwf increased the percentage carbon-molar yield (C-mol%) of
      3HP on consumed glycerol 4.4-fold (20.1 +/- 9.2 C-mol%), compared to the parental
      strain. Increased extracellular methylglyoxal concentrations in the DeltatpiA
      Deltazwf strain indicated that glycerol catabolism was occurring through the
      methylglyoxal pathway, which converts dihydroxyacetone phosphate to pyruvate, as
      predicted by the metabolic model. Since the DeltatpiA Deltazwf strain produced
      abundant 1,3-propanediol as a major byproduct (37.7 +/- 13.2 C-mol%), yqhD, which
      encodes an enzyme involved in the production of 1,3-propanediol, was disrupted in
      the DeltatpiA Deltazwf strain. The 3HP yield of the DeltatpiA Deltazwf DeltayqhD
      strain (33.9 +/- 1.2 C-mol%) was increased 1.7-fold further compared to the
      DeltatpiA Deltazwf strain and by 7.4-fold compared to the parental strain.
      CONCLUSION: This study successfully increased 3HP production by 7.4-fold in the
      DeltatpiA Deltazwf DeltayqhD E. coli strain by the modification of the central
      metabolism, based on metabolic simulation and experimental validation of
      engineered strains.

PMID- 24885134
TI  - Health-service performance of TB treatment for indigenous and non-indigenous
      populations in Brazil: a cross-sectional study.
AB  - BACKGROUND: Health-service evaluation studies are fundamental for proposing
      interventions and ensuring improvements in healthcare quality. The present study
      assesses the performance of health services for indigenous and non-indigenous
      populations with regard to tuberculosis (TB) control. METHODS: Interviews with TB
      patients who underwent treatment between 2009 and 2011 were conducted using the
      Primary Care Assessment Tool adapted for TB care in Brazil. RESULTS: Primary
      healthcare (PHC) was the first treatment for most patients at symptom onset, and
      the diagnoses were typically performed by specialized services. Many patients
      experienced delayed TB diagnoses that required more than three medical
      appointments (51% and 47% for indigenous and non-indigenous populations,
      respectively). Indigenous people received social support, such as basic-needs
      grocery packages (2.19 +/- 1.63 vs. 1.13 +/- 0.49 for non-indigenous people, p <
      0.01) and home visits from health professionals, with an emphasis on the
      performance of directly observed treatment strategies (DOT; 4.57 +/- 0.89 vs.
      1.68 +/- 1.04 for non-indigenous people, p < 0.01). CONCLUSIONS: Regardless of
      the differences between indigenous and non-indigenous populations, the time
      needed to receive a TB diagnosis was unsatisfactory for both groups. Furthermore,
      DOT must be performed with better coverage among non-indigenous patients.

PMID- 24885135
TI  - Impact of a chronic disease self-management program on health care utilization in
      rural communities: a retrospective cohort study using linked administrative data.
AB  - BACKGROUND: Internationally, chronic disease self-management programs (CDSMPs)
      have been widely promoted with the assumption that confident, knowledgeable
      patients practicing self-management behavior will experience improved health and
      utilize fewer healthcare resources. However, there is a paucity of published data
      supporting this claim and the majority of the evidence is based on self-report.
      METHODS: We used a retrospective cohort study using linked administrative health
      data. Data from 104 tele-CDSMP participants from 13 rural and remote communities
      in the province of Ontario, Canada were linked to administrative databases
      containing emergency department (ED) and physician visits and hospitalizations.
      Patterns of health care utilization prior to and after participation in the tele
      CDSMP were compared. Poisson Generalized Estimating Equations regression was used
      to examine the impact of the tele-CDSMP on health care utilization after
      adjusting for covariates. RESULTS: There were no differences in patterns of
      health care utilization before and after participating in the tele-CDSMP. Among
      participants <= 66 years, however, there was a 34% increase in physician visits
      in the 12 months following the program (OR = 1.34, 95% CI 1.11-1.61) and a trend
      for decreased ED visits in those >66 years (OR = 0.59, 95% CI 0.33-1.06).
      CONCLUSIONS: This is the first study to examine health care use following
      participation in the CDSMP in a Canadian population and to use administrative
      data to measure health care utilization. Similar to other studies that used self
      report measures to evaluate health care use we found no differences in health
      care utilization before and after participation in the CDSMP. Future research
      needs to confirm our findings and examine the impact of the CDSMP on health care
      utilization in different age groups to help to determine whether these
      interventions are more effective with select population groups.

PMID- 24885136
TI  - Esthetic outcome of implant-based reconstructions in augmented bone: comparison
      of autologous and allogeneic bone block grafting with the pink esthetic score
      (PES).
AB  - INTRODUCTION: To determine the esthetic outcome of implant-based reconstructions
      after autologous and allogeneic bone grafting. METHODS: From 2003 to 2009, 67
      patients underwent alveolar ridge augmentation and were enrolled in the study, 41
      meet the inclusion criteria and 31 agreed to take part in the study. Patients
      were 18-69 years old (mean: 49.3 +/- 13.8 years), and predominantly female.
      Patients received bone block grafts either autologous (n = 48) (AUBB) or
      allografts (ABB) (n = 19). Implants were inserted 4-7 months (autografts) or 5-6
      months (allografts) after bone grafting. The Pink Esthetic Score (PES) as well as
      radiographic and subjective assessments were employed for the outcome analysis.
      The PES was assessed twice within one month based on digital photographic images
      that were randomly rearranged between evaluations by three independent,
      experienced investigators. RESULTS: Across all observations and investigators,
      the average PES was 7.5 +/- 2.6 without differences between implants inserted in
      auto- and allografted bone, respectively. Patients assessed the allograft
      procedures as less painful and would have repeated it more often. The intra-rater
      reliability was excellent (correlation coefficients 0.7-0.9). The inter-observer
      agreement was lower (correlation coefficients 0.6-0.8). CONCLUSIONS: Bone
      grafting with ABB allografts yields equivalent results to autologous grafting,
      and patients appreciate the omission of bone harvesting. The PES is a reliable
      method but should be performed by the same individual.

PMID- 24885137
TI  - Association of body mass index with risk of acute myocardial infarction and
      mortality in Norwegian male and female patients with suspected stable angina
      pectoris: a prospective cohort study.
AB  - BACKGROUND: A number of previous studies have suggested that overweight or obese
      patients with coronary artery disease (CAD) may have lower morbidity and
      mortality than their leaner counterparts. Few studies have addressed possible
      gender differences, and the results are conflicting. We examined the association
      between body mass index (BMI) and risk of acute myocardial infarction (AMI),
      cardiovascular (CV) death and all-cause mortality in men and women with suspected
      stable angina pectoris. METHOD: The cohort included 4164 patients with suspected
      stable angina undergoing elective coronary angiography between 2000 and 2004.
      Events were registered until the end of 2006. Hazard ratios (HR) (95% confidence
      intervals) were estimated using Cox regression by comparing normal weight (18.5
      24.9 kg/m2) with overweight (25-29.9 kg/m2) and obese (>=30 kg/m2) patients.
      Underweight (<18.5 kg/m2) patients were excluded from the study. RESULTS: Of 4131
      patients with complete data, 72% were males and 75% were diagnosed with
      significant CAD. The mean (standard deviation (SD)) age in the total population
      was 62 (10) years. Mean (SD) BMI was 26.8 (3.9) kg/m2, 34% was normal weight, 48%
      overweight and 19% obese. During follow up, a total of 337 (8.2%) experienced an
      AMI and 302 (7.3%) patients died, of whom 165 (4.0%) died from cardiovascular
      causes. We observed a significant interaction between BMI groups and gender with
      regards to risk of AMI (p = 0.011) and CV death (p = 0.031), but not to risk of
      all-cause mortality; obese men had a multivariate adjusted increased risk of AMI
      (HR 1.80 (1.28, 2.52)) and CV death (HR 1.60 (1.00, 2.55)) compared to normal
      weight men. By contrast, overweight women had a decreased risk of AMI (HR 0.56
      (0.33, 0.98)) compared to normal weight women. The risk of all-cause mortality
      did not differ between BMI categories. CONCLUSION: Compared with normal weight
      subjects, obese men had an increased risk of AMI and CV death, while overweight
      women had a decreased risk of AMI. These findings may potentially explain some of
      the result variation in previous studies reporting on the obesity paradox.

PMID- 24885138
TI  - Genome-wide response to selection and genetic basis of cold tolerance in rice
      (Oryza sativa L.).
AB  - BACKGROUND: Cold stress is an important factor limiting rice yield in many areas
      of high latitude and altitude. Considerable efforts have been taken to
      genetically dissect cold tolerance (CT) in rice using DNA markers. Because of
      possible epistasis and gene * environment interactions associated with identified
      quantitative trait loci, the results of these genetic studies have unfortunately
      not been directly applicable to marker-assisted selection for improved rice CT.
      In this study, we demonstrated the utility of a selective introgression strategy
      for simultaneous improvement and genetic dissection of rice seedling CT. RESULTS:
      A set of japonica introgression lines (ILs) with significantly improved seedling
      CT were developed from four backcross populations based on two rounds of
      selection. Genetic characterization of these cold-tolerant ILs revealed two
      important aspects of genome-wide responses to strong phenotypic selection for
      rice CT: (1) significant over-introgression of donor alleles at 57 loci in 29
      functional genetic units (FGUs) across the rice genome and (2) pronounced non
      random associations between or among alleles at many unlinked CT loci. Linkage
      disequilibrium analyses of the detected CT loci allowed us to construct putative
      genetic networks (multi-locus structures) underlying the seedling CT of rice.
      Each network consisted of a single FGU, with high introgression as the putative
      regulator plus two to three groups of highly associated downstream FGUs. A
      bioinformatics search of rice genomic regions harboring these putative regulators
      identified a small set of candidate regulatory genes that are known to be
      involved in plant stress response. CONCLUSIONS: Our results suggest that CT in
      rice is controlled by multiple pathways. Genetic complementarity between parental
      derived functional alleles at many loci within a given pathway provides an
      appropriate explanation for the commonly observed hidden diversity and
      transgressive segregation of CT and other complex traits in rice.

PMID- 24885139
TI  - Coeliac disease and risk for other autoimmune diseases in patients with Williams
      Beuren syndrome.
AB  - BACKGROUND: A higher prevalence of coeliac disease (CD) has been reported in
      patients with Williams-Beuren syndrome (WBS), though coexistence with other
      autoimmune diseases has not been evaluated. OBJECTIVE: The aim of this study was
      to examine the prevalence of the more frequent autoimmune diseases and organ- and
      non-organ specific autoantibodies in WBS. METHODS: We longitudinally analysed 46
      WBS patients to evaluate the prevalence and co-occurrence of the major
      autoantibodies and HLA typing for CD diagnosis. These data were compared with
      healthy age- and sex-matched controls and Down (DS) and Turner (TS) syndrome
      patients. RESULTS: CD was diagnosed in one (2.2%) WBS patient; this differed
      significantly from DS and TS (respectively, 10.5% and 9.4%; P < 0.005) but not
      from healthy controls (0.6%; P = NS). However, no patients with WBS showed anti
      thyroid antibodies or other organ- and non-organ specific autoantibodies, which
      differed significantly from DS (respectively, 10.5% and 7.0%; P < 0.005) and TS
      (respectively, 9.4% and 9.3%; P < 0.005) patients but not from healthy controls
      (1.1% and 2.3%). The frequencies of CD-specific HLA-DQ heterodimers were not
      significantly higher than controls, even though the WBS patients more frequently
      carried the DQA1*0505 allele (57% vs. 39%; P < 0.05). CONCLUSIONS: CD may not be
      more frequent in patients with WBS. In fact, no evidence of a significantly
      higher prevalence of other autoimmune diseases or positivity of the main organ
      and non-organ specific autoantibodies was found in WBS, such as showed in the
      healthy controls and unlike by the patients with Turner or Down syndrome. This
      should prompt us to better understand the occurrence of CD in WBS. Other studies
      or longer follow-up might be useful to clarify this issue.

PMID- 24885140
TI  - A prospective, blinded evaluation of a video-assisted '4-stage approach' during
      undergraduate student practical skills training.
AB  - BACKGROUND: The 4-stage approach (4-SA) is used as a didactic method for teaching
      practical skills in international courses on resuscitation and the structured
      care of trauma patients. The aim of this study was to evaluate objective and
      subjective learning success of a video-assisted 4-SA in teaching undergraduate
      medical students. METHODS: The participants were medical students learning the
      principles of the acute treatment of trauma patients in their multidiscipline
      course on emergency and intensive care medicine. The participants were quasi-
      randomly divided into two groups. The 4-SA was used in both groups. In the
      control group, all four steps were presented by an instructor. In the study
      group, the first two steps were presented as a video. At the end of the course a
      5-minute objective, structured clinical examination (OSCE) of a simulated trauma
      patient was conducted. The test results were divided into objective results
      obtained through a checklist with 9 dichotomous items and the assessment of the
      global performance rated subjectively by the examiner on a Likert scale from 1 to
      6. RESULTS: 313 students were recruited; the results of 256 were suitable for
      analysis. The OSCE results were excellent in both groups and did not differ
      significantly (control group: median 9, interquantil range (IQR) 8-9, study
      group: median 9, IQR 8-9; p = 0.29). The global performance was rated
      significantly better for the study group (median 1, IQR 1-2 vs. median 2, IQR 1
      3; p < 0.01). The relative knowledge increase, stated by the students in their
      evaluation after the course, was greater in the study group (85% vs. 80%).
      CONCLUSION: It is possible to employ video assistance in the classical 4-SA with
      comparable objective test results in an OSCE. The global performance was
      significantly improved with use of video assistance.

PMID- 24885142
TI  - Drugs foresight 2020: a Delphi expert panel study.
AB  - BACKGROUND: Historically substance misuse has been relatively common in western
      countries, but comparatively few Finns report drug use. The Drugs 2020 study
      aimed at foreseeing changes in the drug situation in Finland by the year 2020.
      METHODS: The Delphi method was used, utilizing drug experts of the EU national
      network in Finland. RESULTS: Marked growth was foreseen in drug use, especially
      in synthetic designer drugs and misuse of medicinal drugs. Significant increase
      was also expected in growing cannabis at home. However, the control of drug
      market was expected to shift more into the hands of organized crime. No consensus
      was reached on how drug prices will develop in the time period. Drug use is
      likely to remain punishable although the use and possession of cannabis may be
      treated less severely. It seems likely that health and social services resources
      will be directed towards medicinal treatment. CONCLUSIONS: Foresight can be
      utilized in preparing for the future; desirable developments can be fostered, and
      measures can be taken to curb probable but undesirable lines of development.
      Based on the results of this study, the experts' view is that it is highly likely
      that the Finnish society will have to prepare for an increase in the demand for
      drug-related care, both in terms of content of the care and financing the
      services. Also, the forecasted increase in the role of legal prescription
      medicine used as intoxicants will call for efforts not only in changing
      prescription practices but in border and police control measures, as well.
      Parallel developments have been foreseen in the UK and Sweden, and it is likely
      that similar trends will actualize also in other western countries.

PMID- 24885141
TI  - The history of the North African mitochondrial DNA haplogroup U6 gene flow into
      the African, Eurasian and American continents.
AB  - BACKGROUND: Complete mitochondrial DNA (mtDNA) genome analyses have greatly
      improved the phylogeny and phylogeography of human mtDNA. Human mitochondrial DNA
      haplogroup U6 has been considered as a molecular signal of a Paleolithic return
      to North Africa of modern humans from southwestern Asia. RESULTS: Using 230
      complete sequences we have refined the U6 phylogeny, and improved the
      phylogeographic information by the analysis of 761 partial sequences. This
      approach provides chronological limits for its arrival to Africa, followed by its
      spreads there according to climatic fluctuations, and its secondary prehistoric
      and historic migrations out of Africa colonizing Europe, the Canary Islands and
      the American Continent. CONCLUSIONS: The U6 expansions and contractions inside
      Africa faithfully reflect the climatic fluctuations that occurred in this
      Continent affecting also the Canary Islands. Mediterranean contacts drove these
      lineages to Europe, at least since the Neolithic. In turn, the European
      colonization brought different U6 lineages throughout the American Continent
      leaving the specific sign of the colonizers origin.

PMID- 24885143
TI  - In vitro antibacterial, antioxidant and cytotoxic activity of acetone leaf
      extracts of nine under-investigated Fabaceae tree species leads to potentially
      useful extracts in animal health and productivity.
AB  - BACKGROUND: The Fabaceae family is the second largest family of medicinal plants,
      containing more than 490 species which are being used as traditional medicine.
      The aim of this study was to determine the antioxidant and antibacterial activity
      as well as the cytotoxicity of acetone leaf extracts of nine tree species from
      the Fabaceae family that have not been investigated well previously for possible
      use in animal health and production. METHODS: The antibacterial activity was
      determined by a serial microdilution method against three Gram-positive and three
      Gram-negative bacteria. Antioxidant activity was determined using free-radical
      scavenging assays. The safety of the extracts was ascertained using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Vero African
      green monkey kidney cells. RESULTS: Six of the nine acetone extracts had
      significant antibacterial activity against at least one of the six bacterial
      species with (MIC 20-80 MUg/mL). The Crotalaria capensis extract had the highest
      activity against Salmonella typhimurium, followed by Indigofera cylindrica with
      MICs of 20 MUg/mL and 40 MUg/mL respectively. The Dalbergia nitidula extract had
      free radical scavenging capacity (IC50 of 9.31+/-2.14 MUg/mL) close to that of
      the positive control Trolox in the DPPH assay. The Xylia torreana extract also
      had high activity (IC50 of 14.56+/-3.96 MUg/mL) in the ABTS assay. There was a
      good correlation between antioxidant activity and total phenolic content (R2
      values>0.8). The extracts had weak or no toxicity to Vero cells, compared to the
      positive control doxorubicin with the LC50 varying from 10.70+/-3.47 to 131.98+/
      24.87 MUg/mL at the concentrations tested. CONCLUSION: Extracts of D. nitidula,
      X. torreana, C. capensis and I. cylindrica had a low cytotoxicity and high
      antimicrobial and/or antioxidant activity. These species are therefore promising
      candidates for the development of useful antimicrobial/antioxidant preparations
      with a low cytotoxicity that may be useful in promoting animal health and
      productivity.

PMID- 24885144
TI  - Anticipated and experienced discrimination amongst people with schizophrenia,
      bipolar disorder and major depressive disorder: a cross sectional study.
AB  - BACKGROUND: The unfair treatment of individuals with severe mental illness has
      been linked to poorer physical and mental health outcomes. Additionally,
      anticipation of discrimination may lead some individuals to avoid participation
      in particular life areas, leading to greater isolation and social
      marginalisation. This study aimed to establish the levels and clinical and socio
      demographic associations of anticipated and experienced discrimination amongst
      those diagnosed with a schizophrenia and comparator severe mental illnesses
      (bipolar and major depressive disorders). METHODS: This study was a cross
      sectional analysis of anticipated and experienced discrimination from 202
      individuals in South London (47% with schizophrenia, 32% with depression and 20%
      with bipolar disorder). RESULTS: 93% of the sample anticipated discrimination and
      87% of participants had experienced discrimination in at least one area of life
      in the previous year. There was a significant association between the
      anticipation and the experience of discrimination. Higher levels of experienced
      discrimination were reported by those of a mixed ethnicity, and those with higher
      levels of education. Women anticipated more discrimination than men. Neither
      diagnosis nor levels of functioning were associated with the extent of
      discrimination. Clinical symptoms of anxiety, depression and suspiciousness were
      associated with more experienced and anticipated discrimination respectively.
      CONCLUSIONS: The unfair treatment of individuals with severe mental illnesses
      remains unacceptably common. Population level interventions are needed to reduce
      levels of discrimination and to safeguard individuals. Interventions are also
      required to assist those with severe mental illness to reduce internalised stigma
      and social avoidance.

PMID- 24885145
TI  - First report of a Chinese strain of coxsackie B3 virus infection in a newborn in
      Germany in 2011: a case report.
AB  - INTRODUCTION: Enteroviruses commonly encounter babies and children and infections
      present in a wide variety of symptoms ranging from asymptomatic infection, benign
      illness, and aseptic meningitis, hand-foot-and-mouth disease to severe life
      threatening disease. Some newborns develop severe disease in the first 2 weeks of
      life and long-term sequelae may occur among survivors. CASE PRESENTATION: We
      present a case report of a Caucasian newborn baby boy with severe encephalitis
      and systemic coxsackievirus B3 infection. The coincidence of maternal infection
      as well as previous mild respiratory illness in his sister suggests either
      prenatal or horizontal postnatal transmission. An electroencephalogram showed a
      severe pathologic pattern with theta-delta-rhythm and spike-wave complexes on
      both hemispheres. We also observed an unusual prolonged viremia for a period of 6
      weeks. Due to the lack of specific antiviral treatment options, the supportive
      management included ventilation and medical treatment of seizures. Phylogenetic
      analysis revealed a genogroup D2 virus previously exclusively detected in China
      and now described in Europe for the first time. CONCLUSIONS: Enteroviral
      infection is an important differential diagnosis in neonatal encephalitis.
      Prolonged viremia must be taken into account and might correlate with disease
      severity. The newly observed enterovirus genotype D2 is spreading from Asia to
      other continents.

PMID- 24885146
TI  - Effectiveness guidance document (EGD) for Chinese medicine trials: a consensus
      document.
AB  - BACKGROUND: There is a need for more Comparative Effectiveness Research (CER) on
      Chinese medicine (CM) to inform clinical and policy decision-making. This
      document aims to provide consensus advice for the design of CER trials on CM for
      researchers. It broadly aims to ensure more adequate design and optimal use of
      resources in generating evidence for CM to inform stakeholder decision-making.
      METHODS: The Effectiveness Guidance Document (EGD) development was based on
      multiple consensus procedures (survey, written Delphi rounds, interactive
      consensus workshop, international expert review). To balance aspects of internal
      and external validity, multiple stakeholders, including patients, clinicians,
      researchers and payers were involved in creating this document. RESULTS:
      Recommendations were developed for "using available data" and "future clinical
      studies". The recommendations for future trials focus on randomized trials and
      cover the following areas: designing CER studies, treatments, expertise and
      setting, outcomes, study design and statistical analyses, economic evaluation,
      and publication. CONCLUSION: The present EGD provides the first systematic
      methodological guidance for future CER trials on CM and can be applied to single
      or multi-component treatments. While CONSORT statements provide guidelines for
      reporting studies, EGDs provide recommendations for the design of future studies
      and can contribute to a more strategic use of limited research resources, as well
      as greater consistency in trial design.

PMID- 24885147
TI  - VAPB/ALS8 interacts with FFAT-like proteins including the p97 cofactor FAF1 and
      the ASNA1 ATPase.
AB  - BACKGROUND: FAF1 is a ubiquitin-binding adaptor for the p97 ATPase and belongs to
      the UBA-UBX family of p97 cofactors. p97 converts the energy derived from ATP
      hydrolysis into conformational changes of the p97 hexamer, which allows the
      dissociation of its targets from cellular structures or from larger protein
      complexes to facilitate their ubiquitin-dependent degradation. VAPB and the
      related protein VAPA form homo- and heterodimers that are anchored in the
      endoplasmic reticulum membrane and can interact with protein partners carrying a
      FFAT motif. Mutations in either VAPB or p97 can cause amyotrophic lateral
      sclerosis, a neurodegenerative disorder that affects upper and lower motor
      neurons. RESULTS: We show that FAF1 contains a non-canonical FFAT motif that
      allows it to interact directly with the MSP domain of VAPB and, thereby, to
      mediate VAPB interaction with p97. This finding establishes a link between two
      proteins that can cause amyotrophic lateral sclerosis when mutated, VAPB/ALS8 and
      p97/ALS14. Subsequently, we identified a similar FFAT-like motif in the ASNA1
      subunit of the transmembrane-domain recognition complex (TRC), which in turn
      mediates ASNA1 interaction with the MSP domain of VAPB. Proteasome inhibition
      leads to the accumulation of ubiquitinated species in VAPB immunoprecipitates and
      this correlates with an increase in FAF1 and p97 binding. We found that VAPB
      interaction with ubiquitinated proteins is strongly reduced in cells treated with
      FAF1 siRNA. Our efforts to determine the identity of the ubiquitinated targets
      common to VAPB and FAF1 led to the identification of RPN2, a subunit of an
      oligosaccharyl-transferase located at the endoplasmic reticulum, which may be
      regulated by ubiquitin-mediated degradation. CONCLUSIONS: The FFAT-like motifs we
      identified in FAF1 and ASNA1 demonstrate that sequences containing a single
      phenylalanine residue with the consensus (D/E)(D/E)FEDAx(D/E) are also proficient
      to mediate interaction with VAPB. Our findings indicate that the repertoire of
      VAPB interactors is more diverse than previously anticipated and link VAPB to the
      function of ATPase complexes such as p97/FAF1 and ASNA1/TRC.

PMID- 24885148
TI  - Primary care at Swiss universities--current state and perspective.
AB  - BACKGROUND: There is increasing evidence that a strong primary care is a
      cornerstone of an efficient health care system. But Switzerland is facing a
      shortage of primary care physicians (PCPs). This pushed the Federal Council of
      Switzerland to introduce a multifaceted political programme to strengthen the
      position of primary care, including its academic role. The aim of this paper is
      to provide a comprehensive overview of the situation of academic primary care at
      the five Swiss universities by the end of year 2012. RESULTS: Although primary
      care teaching activities have a long tradition at the five Swiss universities
      with activities starting in the beginning of the 1980ies; the academic institutes
      of primary care were only established in recent years (2005 - 2009). Only one of
      them has an established chair. Human and financial resources vary substantially.
      At all universities a broad variety of courses and lectures are offered,
      including teaching in private primary care practices with 1331 PCPs involved.
      Regarding research, differences among the institutes are tremendous, mainly
      caused by entirely different human resources and skills. CONCLUSION: So far, the
      activities of the existing institutes at the Swiss Universities are mainly
      focused on teaching. However, for a complete academic institutionalization as
      well as an increased acceptance and attractiveness, more research activities are
      needed. In addition to an adequate basic funding of research positions,
      competitive research grants have to be created to establish a specialty-specific
      research culture.

PMID- 24885149
TI  - Knowledge, attitudes and practice of primary health care physicians towards
      hepatitis B virus in Al-Jouf province, Saudi Arabia.
AB  - BACKGROUND: Primary health care (PHC) physicians will be in the forefront of
      managing hepatitis B (HBV) patients. In Saudi Arabia, very little is known about
      knowledge, attitudes, and practice of PHC physicians towards HBV. This study
      aimed to assess the same parameters. METHODS: During April 2012, a cross
      sectional survey of 180 practitioners aged 38.1 +/- 10.3 years was carried out in
      the primary health care centers (PHCCs) in AlJouf Province of Saudi Arabia. The
      physicians were asked to fill a valid questionnaire containing their
      sociodemographic data, and well-modified questions regarding their knowledge
      base, attitudes, and practice towards HBV. Data was processed and analyzed using
      SPSS (version 17) program, the level of significance was set at P < 0.05. RESULT:
      Response rate 88.3% yielded 159 questionnaires for analysis. Majority of the
      physicians surveyed 128 (80.6%) believed that PHC physicians are capable to
      achieve a major role in the management of HBV. 119 (74.8%) physicians surveyed
      were willing to manage HBV patients and 127 (79.9%) believed that vaccination is
      the most effective means to prevent HBV. There was a statistical significant
      correlation between physicians' qualifications and continuity of care for HBV
      patients (32.8% vs 23.4%; p = 0.006), while continuality of care was more
      frequent among physicians with higher degrees compared to graduate physicians.
      Only 69 (43.4%) physicians were able to interpret HBV seromarkers. The vast
      majority of the physicians 142 (89.3%) were willing to subscribe in regular
      training programs about HBV. CONCLUSION: Suitable attitudes with lack of
      knowledge are found, and practice of our physicians with regard to this
      significant health issue appeared inappropriate. More education focusing on HBV
      is recommended.

PMID- 24885150
TI  - Intracellular trafficking and endocytosis of CXCR4 in fetal mesenchymal
      stem/stromal cells.
AB  - BACKGROUND: Fetal mesenchymal stem/stromal cells (MSC) represent a
      developmentally-advantageous cell type with translational potential.To enhance
      adult MSC migration, studies have focussed on the role of the chemokine receptor
      CXCR4 and its ligand SDF-1 (CXCL12), but more recent work implicates an intricate
      system of CXCR4 receptor dimerization, intracellular localization, multiple
      ligands, splice variants and nuclear accumulation. We investigated the
      intracellular localization of CXCR4 in fetal bone marrow-derived MSC and role of
      intracellular trafficking in CXCR4 surface expression and function. RESULTS: We
      found that up to 4% of human fetal MSC have detectable surface-localized CXCR4.
      In the majority of cells, CXCR4 is located not at the cell surface, as would be
      required for 'sensing' migratory cues, but intracellularly. CXCR4 was identified
      in early endosomes, recycling endosomes, and lysosomes, indicating only a small
      percentage of CXCR4 travelling to the plasma membrane. Notably CXCR4 was also
      found in and around the nucleus, as detected with an anti-CXCR4 antibody directed
      specifically against CXCR4 isoform 2 differing only in N-terminal sequence. After
      demonstrating that endocytosis of CXCR4 is largely independent of endogenously
      produced SDF-1, we next applied the cytoskeletal inhibitors blebbistatin and
      dynasore to inhibit endocytotic recycling. These increased the number of cells
      expressing surface CXCR4 by 10 and 5 fold respectively, and enhanced the number
      of cells migrating to SDF1 in vitro (up to 2.6 fold). These molecules had a
      transient effect on cell morphology and adhesion, which abated after the removal
      of the inhibitors, and did not alter functional stem cell properties.
      CONCLUSIONS: We conclude that constitutive endocytosis is implicated in the
      regulation of CXCR4 membrane expression, and suggest a novel pharmacological
      strategy to enhance migration of systemically-transplanted cells.

PMID- 24885152
TI  - Adaptive accelerated ReaxFF reactive dynamics with validation from simulating
      hydrogen combustion.
AB  - We develop here the methodology for dramatically accelerating the ReaxFF reactive
      force field based reactive molecular dynamics (RMD) simulations through use of
      the bond boost concept (BB), which we validate here for describing hydrogen
      combustion. The bond order, undercoordination, and overcoordination concepts of
      ReaxFF ensure that the BB correctly adapts to the instantaneous configurations in
      the reactive system to automatically identify the reactions appropriate to
      receive the bond boost. We refer to this as adaptive Accelerated ReaxFF Reactive
      Dynamics or aARRDyn. To validate the aARRDyn methodology, we determined the
      detailed sequence of reactions for hydrogen combustion with and without the BB.
      We validate that the kinetics and reaction mechanisms (that is the detailed
      sequences of reactive intermediates and their subsequent transformation to
      others) for H2 oxidation obtained from aARRDyn agrees well with the brute force
      reactive molecular dynamics (BF-RMD) at 2498 K. Using aARRDyn, we then extend our
      simulations to the whole range of combustion temperatures from ignition (798 K)
      to flame temperature (2998K), and demonstrate that, over this full temperature
      range, the reaction rates predicted by aARRDyn agree well with the BF-RMD values,
      extrapolated to lower temperatures. For the aARRDyn simulation at 798 K we find
      that the time period for half the H2 to form H2O product is ~538 s, whereas the
      computational cost was just 1289 ps, a speed increase of ~0.42 trillion (10(12))
      over BF-RMD. In carrying out these RMD simulations we found that the ReaxFF
      COH2008 version of the ReaxFF force field was not accurate for such intermediates
      as H3O. Consequently we reoptimized the fit to a quantum mechanics (QM) level,
      leading to the ReaxFF-OH2014 force field that was used in the simulations. 

PMID- 24885151
TI  - Socioeconomic differences in self-rated health among women: a comparison of St.
      Petersburg to Estonia and Finland.
AB  - INTRODUCTION: Social determinants of health have not been intensively studied in
      Russia, even though the health divide has been clearly demonstrated by an
      increased mortality rate among those with low education. A comparative analysis
      of social health determinants in countries with different historical and economic
      backgrounds may provide useful evidence for addressing health inequalities. We
      aimed to assess socioeconomic determinants of self-rated health in St. Petersburg
      as compared to Estonia and Finland. METHODS: Data for women aged 18-44 were
      extracted from existing population-based surveys and analysed. In St. Petersburg
      the data were originally collected in 2003 (response rate 68%), in Estonia in
      2004-2005 (54%), and in Finland in 2000-2001 (86%). The study samples comprised
      865 women in St. Petersburg, 2141 in Estonia and 1897 in Finland. RESULTS: Self
      rated health was much poorer in St. Petersburg than in Estonia or Finland. High
      education was negatively associated with poor self-rated health in all the
      studied populations; it was (partially) mediated via health behaviour and
      limiting long-term illness only in Estonia and Finland, but not in St.
      Petersburg. High personal income and employment did not associate with poor self
      rated health among St. Petersburg women, as it did in Estonia and Finland. In St.
      Petersburg housewives rather than employed women had better self-rated health,
      unlike the two other areas. CONCLUSION: Women's self-rated health in St.
      Petersburg varied similarly by education but differently by income and employment
      as compared to Estonia and Finland. Education is likely the most meaningful
      dimension of women's socioeconomic position in St. Petersburg. More research is
      needed to further clarify the pathways between socioeconomic position and health
      in Russia.

PMID- 24885154
TI  - Component costs of foodborne illness: a scoping review.
AB  - BACKGROUND: Governments require high-quality scientific evidence to prioritize
      resource allocation and the cost-of-illness (COI) methodology is one technique
      used to estimate the economic burden of a disease. However, variable cost
      inventories make it difficult to interpret and compare costs across multiple
      studies. METHODS: A scoping review was conducted to identify the component costs
      and the respective data sources used for estimating the cost of foodborne
      illnesses in a population. This review was accomplished by: (1) identifying the
      research question and relevant literature, (2) selecting the literature, (3)
      charting, collating, and summarizing the results. All pertinent data were
      extracted at the level of detail reported in a study, and the component cost and
      source data were subsequently grouped into themes. RESULTS: Eighty-four studies
      were identified that described the cost of foodborne illness in humans. Most
      studies (80%) were published in the last two decades (1992-2012) in North America
      and Europe. The 10 most frequently estimated costs were due to illnesses caused
      by bacterial foodborne pathogens, with non-typhoidal Salmonella spp. being the
      most commonly studied. Forty studies described both individual (direct and
      indirect) and societal level costs. The direct individual level component costs
      most often included were hospital services, physician personnel, and drug costs.
      The most commonly reported indirect individual level component cost was
      productivity losses due to sick leave from work. Prior estimates published in the
      literature were the most commonly used source of component cost data. Data
      sources were not provided or specifically linked to component costs in several
      studies. CONCLUSIONS: The results illustrated a highly variable depth and breadth
      of individual and societal level component costs, and a wide range of data
      sources being used. This scoping review can be used as evidence that there is a
      lack of standardization in cost inventories in the cost of foodborne illness
      literature, and to promote greater transparency and detail of data source
      reporting. By conforming to a more standardized cost inventory, and by reporting
      data sources in more detail, there will be an increase in cost of foodborne
      illness research that can be interpreted and compared in a meaningful way.

PMID- 24885153
TI  - Overexpression of IL-17RC associated with ocular sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a chronic inflammatory disease with a systemic
      granulomatous disorder affecting multiple organs including the eye. Both CD4+ T
      cell and macrophage have been linked to the pathogenesis of the disease. METHODS:
      The expression of IL-17RC was measured using FACS,immunohistochemistry and real
      time PCR. Serum level of IL-17 was detected using ELISA. RESULTS: An elevated
      expression of IL-17RC on CD8+ T cells in peripheral blood was found in patients
      with ocular sarcoidosis as compared to healthy controls. Interestingly, we found
      a significant increase in the serum level of IL-17 in patients with ocular
      sarcoidosis as compared to healthy controls, which may be responsible for the
      induction of IL-17RC on CD8+ cells. In addition, IL-17RC appeared only in the
      retinal tissue of the patient with clinically active sarcoidosis. CONCLUSIONS:
      Our results suggested a potential involvement of IL-17RC+CD8+ T cells in
      pathogenesis of ocular sarcoidosis.

PMID- 24885155
TI  - Interleukin-2 alters distribution of CD144 (VE-cadherin) in endothelial cells.
AB  - BACKGROUND: High-dose IL-2 (HDIL2) is approved for the treatment of metastatic
      melanoma and renal cell carcinoma, but its use is limited in part by toxicity
      related to the development of vascular leak syndrome (VLS). Therefore, an
      understanding of the mechanisms that underlie the initiation and progression of
      HDIL2-induced increases in endothelial cell (EC) permeability leading to VLS are
      of clinical importance. METHODS: We established a novel ex vivo approach
      utilizing primary human pulmonary microvascular ECs to evaluate EC barrier
      dysfunction in response to IL-2. RESULTS: Complementary in vitro studies using
      exogenous IL-2 and ex vivo studies using serum from patients treated with IL-2
      demonstrate that HDIL2 induces VLS through CD144 (vascular endothelial (VE)
      cadherin) redistribution. CONCLUSIONS: These findings provide new insight into
      how IL-2 induces VLS and identifies VE-cadherin as a potential target for
      preventing IL-2-related VLS.

PMID- 24885156
TI  - Diagnostic assessment by dynamic contrast-enhanced and diffusion-weighted
      magnetic resonance in differentiation of breast lesions under different imaging
      protocols.
AB  - BACKGROUND: The apparent diffusion coefficient (ADC) is a highly diagnostic
      factor in discriminating malignant and benign breast masses in diffusion-weighted
      magnetic resonance imaging (DW-MRI). The combination of ADC and other pictorial
      characteristics has improved lesion type identification accuracy. The objective
      of this study was to reassess the findings on an independent patient group by
      changing the magnetic field from 1.5-Tesla to 3.0-Tesla. METHODS: This
      retrospective study consisted of a training group of 234 female patients,
      including 85 benign and 149 malignant lesions, imaged using 1.5-Tesla MRI, and a
      test group of 95 female patients, including 19 benign and 85 malignant lesions,
      imaged using 3.0-Tesla MRI. The lesion of interest was segmented from the raw
      image and four sets of measurements describing the morphology, kinetics, DW-MRI,
      and texture of the pictorial properties of each lesion were obtained. Each lesion
      was characterized by 28 features in total. Three classical machine-learning
      algorithms were used to build prediction models on the training group, which
      evaluated the prognostic performance of the multi-sided features in three
      scenarios. To reduce information redundancy, five highly diagnostic factors were
      selected to obtain a compact yet informative characterization of the lesion
      status. RESULTS: Three classification models were built on the training of 1.5
      Tesla patients and were tested on the independent 3.0-Tesla test group. The
      following results were found. i) Characterization of breast masses in a multi
      sided way dramatically increased prediction performance. The usage of all
      features gave a higher performance in both sensitivity and specificity than any
      individual feature groups or their combinations. ii) ADC was a highly effective
      factor in improving the sensitivity in discriminating malignant from benign
      masses. iii) Five features, namely ADC, Sum Average, Entropy, Elongation, and Sum
      Variance, were selected to achieve the highest performance in diagnosis of the
      3.0-Tesla patient group. CONCLUSIONS: The combination of ADC and other multi
      sided characteristics can increase the capability of discriminating malignant and
      benign breast lesions, even under different imaging protocols. The selected
      compact feature subsets achieved a high diagnostic performance and thus are
      promising in clinical applications for discriminating lesion type and for
      personalized treatment planning.

PMID- 24885157
TI  - A sporadic case of unilateral acrokeratoelastoidosis in Saudi Arabia: a case
      report.
AB  - INTRODUCTION: Acrokeratoelastoidosis is a rare condition characterized by
      bilateral multiple hyperkeratotic papules on the palms, soles, and dorsum of the
      hands and feet. To the best of our knowledge, only around 40 cases of
      acrokeratoelastoidosis have been reported worldwide, which are mostly familial.
      CASE PRESENTATION: We report the first case from Saudi Arabia in a 5-year-old
      Saudi girl of Arabian origin, who presented symptoms of acrokeratoelastoidosis
      with unilateral sporadic keratosis on her left hand and left foot. We also review
      the clinical and histopathologic features, etiology, differential diagnosis and
      its treatment. CONCLUSIONS: Given the rarity of acrokeratoelastoidosis, little is
      known about the disease. Further studies are required to understand the
      pathogenesis of the disease for better treatment options. Additional case reports
      of acrokeratoelastoidosis will help in recognizing risk factors, patient
      characteristics, environmental influences and possibly new etiological factors.

PMID- 24885158
TI  - Patients presenting to the hospital with MRSA pneumonia: differentiating
      characteristics and outcomes with empiric treatment.
AB  - BACKGROUND: Concern for MRSA in patients presented to the hospital with pneumonia
      may be overestimated leading to excessive prescribing of empiric anti-MRSA
      therapy. This study aims to identify at-risk patients and treatment outcomes.
      METHODS: Adults hospitalized during 2005-2011 with pneumonia diagnosed within 48
      h of admission were included. Medical charts were retrospectively reviewed for
      relevant data. Patients with MRSA were matched 1:1 to those with non-MRSA
      pathogen or negative culture. A published risk scoring system for MRSA pneumonia
      was applied. RESULTS: 268 elderly patients were included, 134 patients in each
      group. Compared to non-MRSA group, MRSA patients presented more acutely ill (p <
      0.0001) (pneumonia severity index score, 150 vs 93; vasopressor therapy, 34% vs
      6%; ICU admission, 47% vs 13%; and mechanical ventilation, 35% vs 10%) and had
      worse outcomes (p < 0.0001) (time to reach clinical stability, 6 vs 2.5d; length
      of stay, 10 vs 5d; clinical failure, 28% vs 4%; 28-day mortality, 22% vs 3%).
      When applied to our patients, a published risk scoring scheme had 93% sensitivity
      but lacked specificity at 55%; 40% of medium-risk patients did not have MRSA. A
      history of MRSA infection or pneumonia differentiated the latter group. Most MRSA
      patients (66%, 88/134) were treated empirically (primarily vancomycin) but
      outcome was not improved by receipt of empiric therapy. CONCLUSIONS: Use of a
      published risk scoring scheme with additional variables from this study can
      potentially reduce overprescribing of anti-MRSA empiric therapy in patients
      presented to the hospital with pneumonia. Prospective studies evaluating the
      treatment benefit of non-vancomycin alternatives as empiric therapy are needed.

PMID- 24885159
TI  - Factors associated with involvement in nonmetropolitan LGBTQ organizations:
      Proximity? Generativity? Minority stress? Social location?
AB  - Little is known about involvement in LGBTQ organizations. Factors associated with
      involvement in nonmetropolitan LGBTQ organizations were examined using logistic
      regression and survey data from 426 LGBTQ individuals residing in a
      nonmetropolitan region. Involvement was examined in five types of organizations
      (professional, social/recreational, religious, political, and community
      center/charity). The same model testing proximity, generativity, minority stress,
      and social location hypotheses was repeated for each organization type. Results
      demonstrate that the generativity hypothesis is most strongly supported. Indeed,
      emotional attachment to the LGBTQ community significantly increased the odds of
      involvement in every type of organization. However, the factors associated with
      involvement otherwise differed by organization type. Implications for
      organizational leaders are discussed. 

PMID- 24885160
TI  - Impact of the neutrophil response to granulocyte colony-stimulating factor on the
      risk of hemorrhage when used in combination with tissue plasminogen activator
      during the acute phase of experimental stroke.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is a pharmacologic
      agent inducing neutrophil mobilization and a new candidate for neuroprotection
      and neuroregeneration in stroke. Its effects when used in combination with tissue
      plasminogen activator (tPA) were explored during the acute phase of ischemic
      stroke. METHODS: We used a middle cerebral artery occlusion (MCAO) model of
      cerebral ischemia, associated with treatment with tPA, in male spontaneously
      hypertensive rats (SHR). Granulocyte colony-stimulating factor (G-CSF; 60 MUg/kg)
      was injected just before tPA. Neutrophil response in peripheral blood and in the
      infarct area was quantified in parallel to the infarct volume. Protease matrix
      metallopeptidase 9 (MMP-9) release from circulating neutrophils was analyzed by
      immunochemistry and zymography. Vascular reactivity and hemorrhagic volume in the
      infarct area was also assessed. RESULTS: Twenty four hours after ischemia and
      tPA, G-CSF administration induced a significant increase of neutrophils in
      peripheral blood (P <0.05). At 72 hours post-ischemia, G-CSF was significantly
      associated with an increased risk of hemorrhage in the infarct area (2.5 times
      more likely; P <0.05) and significant cerebral endothelium-dependent dysfunction.
      Ex vivo, an increased MMP-9 release from neutrophils after tPA administration
      correlated to the increased hemorrhagic risk (P <0.05). In parallel, G-CSF
      administration was associated with a decreased neutrophil infiltration in the
      infarct area (-50%; P <0.05), with a concomitant significant neuroprotective
      effect (infarct volume: -40%; P <0.05). CONCLUSIONS: We demonstrate that G-CSF
      potentiates the risk of hemorrhage in experimental stroke when used in
      combination with tPA by inducing neutrophilia. This effect is concomitant to an
      increased MMP-9 release from peripheral neutrophils induced by the tPA treatment.
      These results highlight the potential hemorrhagic risk of associating G-CSF to
      thrombolysis during the acute phase of stroke.

PMID- 24885161
TI  - p38 mitogen-activated protein kinase determines the susceptibility to cigarette
      smoke-induced emphysema in mice.
AB  - BACKGROUND: There is a need for agents that suppress inflammation and progression
      of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase
      (p38 MAPK) has been associated with this disorder, and several inhibitors of this
      cascade are in clinical trials for its treatment, but their efficacy and utility
      are unknown. This study evaluated the relationship between p38 MAPK activation
      and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its
      inhibition ameliorated the lung inflammation and injury in murine models of
      cigarette smoke exposure. METHODS: In acute and chronic CS exposure, the
      activation and expression of p38 MAPK in the lungs, as well as lung inflammation
      and injury (proteinase production, apoptosis, and oxidative DNA damage), were
      compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW
      (emphysema-resistant). The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was
      administrated intra-peritoneally to C57BL/6 mice, to examine whether it
      ameliorated cigarette smoke-induced lung inflammation and injury. RESULTS: Acute
      CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF
      alpha and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative
      DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was
      significantly activated and up-regulated by both acute and chronic CS exposure in
      C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in
      C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW
      mice. SB203580 significantly attenuated lung inflammation (neutrophil
      infiltration, mRNA expressions of TNF-alpha and MIP-2, protein levels of KC, MIP
      1alpha, IL-1beta, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA
      damage, and apoptosis caused by acute CS exposure. CONCLUSIONS: Cigarette smoke
      activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced
      emphysema. Its selective inhibition ameliorated lung inflammation and injury in a
      murine model of cigarette smoke exposure. p38 MAPK pathways are a possible
      molecular target for the treatment of chronic obstructive pulmonary disease.

PMID- 24885162
TI  - Alcohol dehydrogenases from Kluyveromyces marxianus: heterologous expression in
      Escherichia coli and biochemical characterization.
AB  - BACKGROUND: Kluyveromyces marxianus has recently become a species of interest for
      ethanol production since it can produce ethanol at high temperature and on a wide
      variety of substrates. However, the reason why this yeast can produce ethanol at
      high temperature is largely unknown. RESULTS: The ethanol fermentation capability
      of K. marxianus GX-UN120 at 40 degrees S was found to be the same as that of
      Saccharomyces cerevisiae at 34 degrees S. Zymogram analysis showed that alcohol
      dehydrogenase 1 (KmAdh1) was largely induced during ethanol production, KmAdh4
      was constitutively expressed at a lower level and KmAdh2 and KmAdh3 were almost
      undetectable. The genes encoding the four alcohol dehydrogenases (ADHs) were
      cloned from strain GX-UN120. Each KmADH was expressed in Escherichia coli and
      each recombinant protein was digested with enterokinase to remove the fusion
      protein. The optimum pH of the purified recombinant KmAdh1 was 8.0 and that of
      KmAdh2, KmAdh3 and KmAdh4 was 7.0. The optimum temperatures of KmAdh1, KmAdh2,
      KmAdh3 and KmAdh4 were 50, 45, 55 and 45 degrees C, respectively. The K(m) values
      of the recombinant KmAdh1 and KmAdh2 were 4.0 and 1.2 mM for acetaldehyde and
      39.7 and 49.5 mM for ethanol, respectively. The V(max) values of the recombinant
      KmAdh1 and KmAdh2 were 114.9 and 21.6 MUmol min-1 mg-1 for acetaldehyde and 57.5
      and 1.8 MUmol min-1 mg-1 for ethanol, respectively. KmAdh3 and KmAdh4 catalyze
      the oxidation reaction of ethanol to acetaldehyde but not the reduction reaction
      of acetaldehyde to ethanol, and the K(m) values of the recombinant KmAdh3 and
      KmAdh4 were 26.0 and 17.0 mM for ethanol, respectively. The V(max) values of the
      recombinant KmAdh3 and KmAdh4 were 12.8 and 56.2 MUmol min-1 mg-1 for ethanol,
      respectively. CONCLUSION: These data in this study collectively indicate that
      KmAdh1 is the primary ADH responsible for the production of ethanol from the
      reduction of acetaldehyde in K. marxianus. The relatively high optimum
      temperature of KmAdh1 may partially explain the ability of K. marxianus to
      produce ethanol at high temperature. Understanding the biochemical
      characteristics of KmAdhs will enhance our fundamental knowledge of the
      metabolism of ethanol fermentation in K. marxianus.

PMID- 24885163
TI  - Real-time imaging of ATP release induced by mechanical stretch in human airway
      smooth muscle cells.
AB  - Airway smooth muscle (ASM) cells within the airway walls are continually exposed
      to mechanical stimuli, and exhibit various functions in response to these
      mechanical stresses. ATP acts as an extracellular mediator in the airway.
      Moreover, extracellular ATP is considered to play an important role in the
      pathophysiology of asthma and chronic obstructive pulmonary disease. However, it
      is not known whether ASM cells are cellular sources of ATP secretion in the
      airway. We therefore investigated whether mechanical stretch induces ATP release
      from ASM cells. Mechanical stretch was applied to primary human ASM cells
      cultured on a silicone chamber coated with type I collagen using a stretching
      apparatus. Concentrations of ATP in cell culture supernatants measured by
      luciferin-luciferase bioluminescence were significantly elevated by cyclic
      stretch (12 and 20% strain). We further visualized the stretch-induced ATP
      release from the cells in real time using a luminescence imaging system, while
      acquiring differential interference contrast cell images with infrared optics.
      Immediately after a single uniaxial stretch for 1 second, strong ATP signals were
      produced by a certain population of cells and spread to surrounding spaces. The
      cyclic stretch-induced ATP release was significantly reduced by inhibitors of
      Ca(2+)-dependent vesicular exocytosis, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid tetraacetoxymethyl ester, monensin, N-ethylmaleimide, and
      bafilomycin. In contrast, the stretch-induced ATP release was not inhibited by a
      hemichannel blocker, carbenoxolone, or blockade of transient receptor potential
      vanilloid 4 by short interfering RNA transfection or ruthenium red. These
      findings reveal a novel property of ASM cells: mechanically induced ATP release
      may be a cellular source of ATP in the airway. 

PMID- 24885164
TI  - The Argus II prosthesis facilitates reaching and grasping tasks: a case series.
AB  - BACKGROUND: To evaluate the reach-to-grasp performance of patients fitted with an
      epiretinal artifical retina device. METHODS: This was a hospital-based case
      series consisting of six patients fitted with the Argus II (Second Sight Medical
      Products Inc, California, USA) retinal prosthesis. Participants were asked to
      reach out and pick up a high-contrast cuboid object with the prosthesis in the
      'On', 'Off' or 'Scrambled' setting presented in a randomised order. The
      'Scrambled' setting consisted of a random, scattered signal presented to the
      prosthesis. The session was repeated after a 4-6 week period. Hand movements were
      measured using motion detection cameras. The number of successful object grasps
      was calculated. RESULTS: The number of successful grasps was greater with the
      prosthesis in the 'On' setting (visit 1: median [interquartile range] percentage
      success: 'Off' = 0 [0 to 50]%, 'On' = 69 [67 to 95]%, 'Scrambled' = 59 [42 to
      95]%; Friedman Chi-squared test statistic 6.5, p = 0.04; visit 2 median [IQR]
      percentage success: 'Off' = 0 [0 to 25]%, 'On' = 69 [53 to 100]%, 'Scrambled' =
      28 [13 to 63]%; Friedman Chi-squared test statistic 8.4, p= 0.02). CONCLUSIONS:
      The use of an electronic retinal prosthesis facilitates reach-and-grasp
      performance. Further work should explore how performance can be improved with
      targeted rehabilitation.

PMID- 24885165
TI  - A web-based protein interaction network visualizer.
AB  - BACKGROUND: Interaction between proteins is one of the most important mechanisms
      in the execution of cellular functions. The study of these interactions has
      provided insight into the functioning of an organism's processes. As of October
      2013, Homo sapiens had over 170000 Protein-Protein interactions (PPI) registered
      in the Interologous Interaction Database, which is only one of the many public
      resources where protein interactions can be accessed. These numbers exemplify the
      volume of data that research on the topic has generated. Visualization of large
      data sets is a well known strategy to make sense of information, and protein
      interaction data is no exception. There are several tools that allow the
      exploration of this data, providing different methods to visualize protein
      network interactions. However, there is still no native web tool that allows this
      data to be explored interactively online. RESULTS: Given the advances that web
      technologies have made recently it is time to bring these interactive views to
      the web to provide an easily accessible forum to visualize PPI. We have created a
      Web-based Protein Interaction Network Visualizer: PINV, an open source, native
      web application that facilitates the visualization of protein interactions
      (http://biosual.cbio.uct.ac.za/pinv.html). We developed PINV as a set of
      components that follow the protocol defined in BioJS and use the D3 library to
      create the graphic layouts. We demonstrate the use of PINV with multi-organism
      interaction networks for a predicted target from Mycobacterium tuberculosis, its
      interacting partners and its orthologs. CONCLUSIONS: The resultant tool provides
      an attractive view of complex, fully interactive networks with components that
      allow the querying, filtering and manipulation of the visible subset. Moreover,
      as a web resource, PINV simplifies sharing and publishing, activities which are
      vital in today's research collaborative environments. The source code is freely
      available for download at https://github.com/4ndr01d3/biosual.

PMID- 24885166
TI  - NO, via its target Cx37, modulates calcium signal propagation selectively at
      myoendothelial gap junctions.
AB  - BACKGROUND: Gap junctional calcium signal propagation (transfer of calcium or a
      calcium releasing messenger via gap junctions) between vascular cells has been
      shown to be involved in the control of vascular tone. We have shown before that
      nitric oxide (NO) inhibits gap junctional communication in HeLa cells exclusively
      expressing connexin 37 (HeLa-Cx37) but not in HeLa-Cx40 or HeLa-Cx43. Here we
      studied the effect of NO on the gap junctional calcium signal propagation in
      endothelial cells which, in addition to Cx37, also express Cx40 and Cx43.
      Furthermore, we analyzed the impact of NO on intermuscle and on myoendothelial
      gap junction-dependent calcium signal propagation. Since specific effects of NO
      at one of these three junctional areas (interendothelial/ myoendothelial/
      intermuscle) may depend on a differential membrane localization of the connexins,
      we also studied the distribution of the vascular connexins in small resistance
      arteries. RESULTS: In endothelial (HUVEC) or smooth muscle cells (HUVSMC) alone,
      NO did not affect gap junctional Ca2+ signal propagation as assessed by analyzing
      the spread of Ca2+ signals after mechanical stimulation of a single cell. In
      contrast, at myoendothelial junctions, it decreased Ca2+ signal propagation in
      both directions by about 60% (co-cultures of HUVEC and HUVSMC). This resulted in
      a longer maintenance of calcium elevation at the endothelial side and a faster
      calcium signal propagation at the smooth muscle side, respectively.
      Immunohistochemical stainings (confocal and two-photon-microscopy) of cells in co
      cultures or of small arteries revealed that Cx37 expression was relatively higher
      in endothelial cells adjoining smooth muscle (culture) or in potential areas of
      myoendothelial junctions (arteries). Accordingly, Cx37 - in contrast to Cx40 -
      was not only expressed on the endothelial surface of small arteries but also in
      deeper layers (corresponding to the internal elastic lamina IEL). Holes of the
      IEL where myoendothelial contacts can only occur, stained significantly more
      frequently for Cx37 and Cx43 than for Cx40 (endothelium) or Cx45 (smooth muscle).
      CONCLUSION: NO modulates the calcium signal propagation specifically between
      endothelial and smooth muscle cells. The effect is due to an augmented
      distribution of Cx37 towards myoendothelial contact areas and potentially
      counteracts endothelial Ca2+ signal loss from endothelial to smooth muscle cells.
      This targeted effect of NO may optimize calcium dependent endothelial vasomotor
      function.

PMID- 24885167
TI  - Attitudes of medical students towards incentives offered by pharmaceutical
      companies -- perspective from a developing nation -- a cross-sectional study.
AB  - BACKGROUND: A training physician has his first interaction with a pharmaceutical
      representative during medical school. Medical students are often provided with
      small gifts such as pens, calendars and books, as well as free lunches as part of
      drug promotion offers. Ethical impact of these transactions as perceived by young
      medical students has not been investigated in Pakistan before. This study aimed
      to assess the association of socio-demographic variables with the attitudes of
      medical students towards pharmaceutical companies and their incentives. METHODS:
      As part of a cross-sectional survey, a validated questionnaire previously used
      for assessing attitude of medical students towards pharmaceutical industry, was
      modified, pre-tested and distributed among consenting clinical year students at
      DUHS and AKU. Questions included acceptability of pharmaceutically sponsored
      gifts, events and tuition fee, and their impact on future prescription. Responses
      were graded as agree, disagree or neutral which were then scored according to the
      AMSA guidelines of ethical conduct. RESULTS: Out of a total of 353 targeted
      students 303 responded, corresponding to a response rate of 85.8%. Responses
      indicated that 42.7% students believed in no interaction with drug companies
      during medical school. However, 81% of students favored pharmaceutical
      sponsorship of student-body events/seminars at medical colleges. More than one
      third of the students were comfortable receiving gifts from drug companies.
      Overall, the results of this study offer an interesting comparison between the
      students of a private medical school (AKU) and a public medical school (DUHS);
      AKU students exhibited a greater degree of mistrust towards drug information
      provided by pharmaceutical companies compared to DUHS students (p = 0.040).
      Furthermore, when asked if there was a need to incorporate guidelines in the
      undergraduate curriculum with regard to interaction with drug companies, 84.2%
      students at AKU agreed, compared to 54.9% at DUHS. Medical student Attitude
      Scores are more or less similar to each other independent of their various
      demographical differences. CONCLUSION: This study highlights that medical
      students in our population have a high level of acceptability towards incentives
      offered by pharmaceutical industry and that formal guidance regarding the subject
      should be incorporated into medical curriculum.

PMID- 24885168
TI  - Use of an automated blood culture system (BD BACTECTM) for diagnosis of
      prosthetic joint infections: easy and fast.
AB  - BACKGROUND: For the diagnosis of prosthetic joint infection (PJI) automated
      BACTECTM blood culture bottle methods have comparable sensitivity, specificity
      and a shorter time to positivity than traditional cooked meat enrichment broth
      methods. We evaluate the culture incubation period required to maximise
      sensitivity and specificity of microbiological diagnosis, and the ability of
      BACTECTM to detect slow growing Propionibacteria spp. METHODS: Multiple
      periprosthetic tissue samples taken by a standardised method from 332 patients
      undergoing prosthetic joint revision arthroplasty were cultured for 14 days,
      using a BD BACTECTM instrumented blood culture system, in a prospective study
      from 1st January to 31st August 2012. The "gold standard" definition for PJI was
      the presence of at least one histological criterion, the presence of a sinus
      tract or purulence around the device. Cases where > =2 samples yielded
      indistinguishable isolates were considered culture-positive. 1000 BACTECTM bottle
      cultures which were negative after 14 days incubation were sub-cultured for
      Propionibacteria spp. RESULTS: 79 patients fulfilled the definition for PJI, and
      66 of these were culture-positive. All but 1 of these 66 culture-positive cases
      of PJI were detected within 3 days of incubation. Only one additional (clinically
      insignificant) Propionibacterium spp. was identified on terminal subculture of
      1000 bottles. CONCLUSIONS: Prolonged microbiological culture for 2 weeks is
      unnecessary when using BACTECTM culture methods. The majority of clinically
      significant organisms grow within 3 days, and Propionibacteria spp. are
      identified without the need for terminal subculture. These findings should
      facilitate earlier decisions on final antimicrobial prescribing.

PMID- 24885169
TI  - Histological comparison between preoperative and surgical specimens of non-small
      cell lung cancer for distinguishing between "squamous" and "non-squamous" cell
      carcinoma.
AB  - BACKGROUND: Non-small cell lung cancers (NSCLCs) are frequently heterogeneous and
      in approximately 70% of cases, NSCLCs are diagnosed and staged by small biopsies
      or cytology rather than by examination of surgically resected specimens. Thus, in
      most patients, the diagnosis is established based on examination of preoperative
      specimens alone. Recently, classification of NSCLC into pathologic subtypes has
      been shown to be important for selecting the appropriate systemic therapy, from
      both the point of view of treatment efficacy and prevention of toxicity. METHODS:
      We retrospectively reviewed the data of 225 patients to compare the preoperative
      classification of the NSCLC subtype on biopsy specimens with the postoperative
      classification based on examination of the resected specimens, in order to
      compare the accuracy of the two for the diagnosis of various histological
      subtypes of NSCLC. RESULTS: In 169 of the 225 (75.1%) patients, the preoperative
      diagnosis was definite malignancy. Histologically, the final pathologic diagnosis
      made from the surgical specimens was adenocarcinoma (ADC) in 169 patients, and in
      75.5% of these cases, the diagnosis was concordant with the preoperative
      diagnosis. Among the patients who had squamous cell carcinoma (SQC) in the
      preoperative specimens, the diagnosis was concordant with the preoperative
      diagnosis in 65.7% of cases. Misclassified preoperative biopsies included an even
      number of SQCs and ADCs, with all the misclassified biopsies being ADCs
      morphologically mimicking SQC due to solid growth. Significantly higher
      specificity, negative predictive value and accuracy were observed for the
      diagnosis of SQC. CONCLUSIONS: Our study suggested that the concordance rates for
      diagnosis of the NSCLC subtypes, especially the "squamous" or "non-squamous"
      histologies, between preoperative and surgical specimens were satisfactory, as
      compared with previous reports. Therefore, pretreatment diagnosis of lung cancer
      using small samples is reasonable for selecting the optimal treatment. However,
      in order not to lose the opportunity for selecting an effective treatment, we
      should be aware that the diagnosis in preoperative small samples might be
      different from that based on examination of the surgical specimens. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2032698427120488.

PMID- 24885170
TI  - MicroRNA expression profiling of the fifth-instar posterior silk gland of Bombyx
      mori.
AB  - BACKGROUND: The growth and development of the posterior silk gland and the
      biosynthesis of the silk core protein at the fifth larval instar stage of Bombyx
      mori are of paramount importance for silk production. RESULTS: Here, aided by
      next-generation sequencing and microarry assay, we profile 1,229 microRNAs
      (miRNAs), including 728 novel miRNAs and 110 miRNA/miRNA* duplexes, of the
      posterior silk gland at the fifth larval instar. Target gene prediction yields
      14,222 unique target genes from 1,195 miRNAs. Functional categorization
      classifies the targets into complex pathways that include both cellular and
      metabolic processes, especially protein synthesis and processing. CONCLUSION: The
      enrichment of target genes in the ribosome-related pathway indicates that miRNAs
      may directly regulate translation. Our findings pave a way for further functional
      elucidation of these miRNAs and their targets in silk production.

PMID- 24885171
TI  - Radiographic study of iliac screw passages.
AB  - BACKGROUND: The optimal iliac screw path was determined to provide references for
      lumbosacral-pelvic reconstruction. METHODS: Radiographic data of 100 patients
      with normal pelvis were selected for this study. Four paths were designed. Paths
      A, B, and C were from the starting point of the crossing point of the chiotic
      line and posterior iliac crest (CLIC, located at 24.0 mm above the posterior
      superior iliac spine) to the upper edge of the acetabulum, anterior inferior
      iliac spine, and acetabulum center, respectively. Path D was from the starting
      point of the posterior superior iliac spine to the anterior inferior iliac spine.
      The lengths of the different paths of screw passage and bone plate thicknesses of
      two narrow places were measured and analyzed. RESULTS: Paths A, B, and D were
      approximately equal in length, but the thickness of the iliac plate in path A was
      significantly thicker than those in paths B and D. No significant difference was
      found between the iliac thickness of paths A and C, but the passage length of
      path A was significantly longer than that of path C. CONCLUSION: Path A had the
      longest passage length and thickest iliac plate and could accommodate the
      relatively longest and thickest iliac screw. Thus, path A was the optimal iliac
      screw passage.

PMID- 24885172
TI  - Resolution of a fungal mycotic aneurysm after a contaminated steroid injection: a
      case report.
AB  - BACKGROUND: In the past ten years there have been three separate outbreaks of
      fungal contaminated steroid injections from compounding pharmacies. The 2012
      outbreak of central nervous system fungal infections associated with contaminated
      methylprednisolone produced by a United States compounding pharmacy has led to
      750 infections (151 with meningitis and paraspinal infections and 325 cases with
      paraspinal infections without meningitis) and 64 deaths as of October 23, 2013.
      Exserohilum rostratum has been the predominant pathogen identified by culture,
      polymerase chain reaction or antibody tests. According to previous reports,
      cerebral involvement with phaeohyphomycosis has a high risk of morbidity and
      mortality. CASE PRESENTATION: We report a 41 year-old Caucasian woman who
      received a lumbar methylprednisolone injection from a contaminated lot in August
      2012. She was diagnosed with fungal meningitis by cerebrospinal fluid pleocytosis
      and positive (1, 3) beta-D-glucan after cultures and polymerase chain reaction
      were negative. Two weeks after onset of therapy, she developed a 4.1 mm superior
      cerebellar artery mycotic aneurysm associated with new stroke symptoms, which
      resolved with thirty-two weeks of antifungal treatment. CONCLUSIONS: This is the
      rare case report of successful medical management of a cerebral mycotic aneurysm
      with stroke symptoms related to a presumed phaeohyphomycosis in an
      immunocompetent individual. Further studies are needed to determine the utility
      of cerebrospinal fluid (1, 3) beta-D-glucan in diagnosing and monitoring patients
      with meningitis thought to be related to fungal infection.

PMID- 24885173
TI  - Persistence of microbial communities including Pseudomonas aeruginosa in a
      hospital environment: a potential health hazard.
AB  - BACKGROUND: The persistence of microbial communities and how they change in
      indoor environments is of immense interest to public health. Moreover, hospital
      acquired infections are significant contributors to morbidity and mortality.
      Evidence suggests that, in hospital environments agent transfer between surfaces
      causes healthcare associated infections in humans, and that surfaces are an
      important transmission route and may act as a reservoir for some of the
      pathogens.This study aimed to evaluate the diversity of microorganisms that
      persist on noncritical equipment and surfaces in a main hospital in Portugal, and
      are able to grow in selective media for Pseudomonas, and relate them with the
      presence of Pseudomonas aeruginosa. RESULTS: During 2 years, a total of 290
      environmental samples were analyzed, in 3 different wards. The percentage of
      equipment in each ward that showed low contamination level varied between 22% and
      38%, and more than 50% of the equipment sampled was highly contaminated. P.
      aeruginosa was repeatedly isolated from sinks (10 times), from the taps' biofilm
      (16 times), and from the showers and bedside tables (two times). Two ERIC clones
      were isolated more than once. The contamination level of the different taps
      analyzed showed correlation with the contamination level of the hand gels
      support, soaps and sinks. Ten different bacteria genera were frequently isolated
      in the selective media for Pseudomonas. Organisms usually associated with
      nosocomial infections as Stenotrophomonas maltophilia, Enterococcus feacalis,
      Serratia nematodiphila were also repeatedly isolated on the same equipment.
      CONCLUSIONS: The environment may act as a reservoir for at least some of the
      pathogens implicated in nosocomial infections. The bacterial contamination level
      was related to the presence of humidity on the surfaces, and tap water (biofilm)
      was a point of dispersion of bacterial species, including potentially pathogenic
      organisms. The materials of the equipment sampled could not be related to the
      microbial contamination level. The presence of a disinfectant in the isolation
      medium suggests that the number of microorganism in the environment could be
      higher and shows the diversity of disinfectant resistant species. The statistical
      analysis suggests that the presence of bacteria could increase the risk of
      transmission by hand manipulation.

PMID- 24885174
TI  - Burden of multimorbidity, socioeconomic status and use of health services across
      stages of life in urban areas: a cross-sectional study.
AB  - BACKGROUND: The burden of chronic conditions and multimorbidity is a growing
      health problem in developed countries. The study aimed to determine the estimated
      prevalence and patterns of multimorbidity in urban areas of Catalonia, stratified
      by sex and adult age groups, and to assess whether socioeconomic status and use
      of primary health care services were associated with multimorbidity. METHODS: A
      cross-sectional study was conducted in Catalonia. Participants were adults (19+
      years) living in urban areas, assigned to 251 primary care teams. MAIN OUTCOME:
      multimorbidity (>=2 chronic conditions). Other variables: sex (male/female), age
      (19-24; 25-44; 45-64; 65-79; 80+ years), socioeconomic status (quintiles), number
      of health care visits during the study. RESULTS: We included 1,356,761 patients;
      mean age, 47.4 years (SD: 17.8), 51.0% women. Multimorbidity was present in 47.6%
      (95% CI 47.5-47.7) of the sample, increasing with age in both sexes but
      significantly higher in women (53.3%) than in men (41.7%). Prevalence of
      multimorbidity in each quintile of the deprivation index was higher in women than
      in men (except oldest group). In women, multimorbidity prevalence increased with
      quintile of the deprivation index. Overall, the median (interquartile range)
      number of primary care visits was 8 (4-14) in multimorbidity vs 1 (0-4) in non
      multimorbidity patients. The most prevalent multimorbidity pattern beyond 45
      years of age was uncomplicated hypertension and lipid disorder. Compared with the
      least deprived group, women in other quintiles of the deprivation index were more
      likely to have multimorbidity than men until 65 years of age. The odds of
      multimorbidity increased with number of visits in all strata. CONCLUSIONS: When
      all chronic conditions were included in the analysis, almost 50% of the adult
      urban population had multimorbidity. The prevalence of multimorbidity differed by
      sex, age group and socioeconomic status. Multimorbidity patterns varied by life
      stage and sex; however, circulatory-endocrine-metabolic patterns were the most
      prevalent multimorbidity pattern after 45 years of age. Women younger than 80
      years had greater prevalence of multimorbidity than men, and women's
      multimorbidity prevalence increased as socioeconomic status declined in all age
      groups. Identifying multimorbidity patterns associated with specific age-related
      life-stages allows health systems to prioritize and to adapt clinical management
      efforts by age group.

PMID- 24885175
TI  - Increased mtDNA mutations with aging promotes amyloid accumulation and brain
      atrophy in the APP/Ld transgenic mouse model of Alzheimer's disease.
AB  - BACKGROUND: The role of mitochondrial dysfunction has long been implicated in age
      related brain pathology, including Alzheimer's disease (AD). However, the
      mechanism by which mitochondrial dysfunction may cause neurodegeneration in AD is
      unclear. To model mitochondrial dysfunction in vivo, we utilized mice that harbor
      a knockin mutation that inactivates the proofreading function of mitochondrial
      DNA polymerase gamma (PolgA D257A), so that these mice accumulate mitochondrial
      DNA mutations with age. PolgA D257A mice develop a myriad of mitochondrial
      bioenergetic defects and physical phenotypes that mimic premature ageing, with
      subsequent death around one year of age. RESULTS: We crossed the D257A mice with
      a well-established transgenic AD mouse model (APP/Ld) that develops amyloid
      plaques. We hypothesized that mitochondrial dysfunction would affect Abeta
      synthesis and/or clearance, thus contributing to amyloidogenesis and triggering
      neurodegeneration. Initially, we discovered that Abeta42 levels along with
      Abeta42 plaque density were increased in D257A; APP/Ld bigenic mice compared to
      APP/Ld monogenic mice. Elevated Abeta production was not responsible for
      increased amyloid pathology, as levels of BACE1, PS1, C99, and C83 were unchanged
      in D257A; APP/Ld compared to APP/Ld mice. However, the levels of a major Abeta
      clearance enzyme, insulin degrading enzyme (IDE), were reduced in mice with the
      D257A mutation, suggesting this as mechanism for increased amyloid load. In the
      presence of the APP transgene, D257A mice also exhibited significant brain
      atrophy with apparent cortical thinning but no frank neuron loss. D257A; APP/Ld
      mice had increased levels of 17 kDa cleaved caspase-3 and p25, both indicative of
      neurodegeneration. Moreover, D257A; APP/Ld neurons appeared morphologically
      disrupted, with swollen and vacuolated nuclei. CONCLUSIONS: Overall, our results
      implicate synergism between the effects of the PolgA D257A mutation and Abeta in
      causing neurodegeneration. These findings provide insight into mechanisms of
      mitochondrial dysfunction that may contribute to the pathogenesis of AD via
      decreased clearance of Abeta.

PMID- 24885176
TI  - An examination of exposure and avoidance behavior related to second-hand
      cigarette smoke among adolescent girls in Canada.
AB  - BACKGROUND: Although rates of tobacco use and exposure to second-hand smoke (SHS)
      are declining in Canada, SHS exposure among non-smoking adolescents remains high.
      This study aimed to describe frequency, locations, and avoidance behavior related
      to SHS exposure among adolescent girls in British Columbia, Canada. METHODS: Data
      were analyzed from 841 adolescent girls aged 13 to 15 years old who completed an
      internet-delivered survey as part of a cohort study examining SHS exposure and
      substance use. Measures assessed demographics, smoking behavior and intentions,
      frequency and locations of SHS exposure, and avoidance behavior related to SHS.
      RESULTS: Excluding their own smoking, 27% of girls reported exposure at least
      once a week and an additional 17% reported daily or almost daily exposure over
      the past month. Among girls who reported daily or almost daily exposure, the
      locations of most frequent levels of high exposure were in the home, at or near
      school, inside a vehicle, and outdoor public places. Avoidance behavior related
      to SHS exposure significantly differed by overall SHS exposure in the past month.
      CONCLUSIONS: Despite historically low smoking rates, many adolescent girls
      continue to report regular SHS exposure in multiple locations in British
      Columbia. Girls with the most frequent exposure were significantly less likely to
      report habitual avoidance behavior related to SHS compared to those less
      frequently exposed. This study elucidates settings of high SHS exposure among
      adolescent girls that could be targeted in future policy interventions.
      Additionally, future interventions could target adolescent girls who are
      frequently exposed to SHS and report infrequent avoidance behavior around their
      SHS exposure.

PMID- 24885177
TI  - The relationship between neurocognition and symptomatology in people with
      schizophrenia: social cognition as the mediator.
AB  - BACKGROUND: The relationship between neurocognition and symptomatology in people
      with schizophrenia has been established. The present study examined whether
      social cognition could mediate this relationship. METHODS: There were 119
      participants (58 people with paranoid schizophrenia and 61 healthy controls)
      participated in this study. Neurocognition was assessed by Raven's Progressive
      Matrices Test, the Judgment of Line Orientation Test, and the Tower of London
      Test. Psychiatric symptoms in people with schizophrenia were assessed by the
      Positive and Negative Syndrome Scale. Social cognition was measured by the Faux
      Pas Test, the "Reading the Mind in the Eyes" Test, and the Interpersonal
      Reactivity Index. RESULTS: Results were consistent with previous findings that
      neurocognition and social cognition were impaired in the clinical participants. A
      novel observation is that social cognition significantly mediated the
      relationship between neurocognition and symptomatology. CONCLUSIONS: These
      findings suggest that neurocognitive deficits predispose people with
      schizophrenia to worse psychiatric symptoms through the impairment of social
      cognition. Findings of the present study provide important insight into a
      functional model of schizophrenia that could guide the development of cost
      effective interventions for people with schizophrenia.

PMID- 24885178
TI  - Exposure to nature versus relaxation during lunch breaks and recovery from work:
      development and design of an intervention study to improve workers' health, well
      being, work performance and creativity.
AB  - BACKGROUND: The objective of this research project is to understand and to
      improve workers' recovery from work stress. Although recovery during lunch breaks
      is the most common within-workday break, it has received only minor research
      attention. Therefore, we will study whether lunch breaks including a relaxation
      session or exposure to nature have more favorable outcomes than usually spent
      lunch breaks concerning: a) recovery processes, b) health, c) well-being, d) job
      performance and e) creativity. We approach recovery by combining the theoretical
      frameworks of work and environmental psychology. METHODS/DESIGN: We conduct an
      intervention study in a sample of 268 knowledge-workers who engage in different
      lunch break activities for 15-minutes per day, two weeks in a row. We randomly
      assign participants to three experimental conditions: 1) exposure to nature, 2)
      relaxation and 3) control group (lunch break spent as usual). Online
      questionnaires before and after the intervention assess long term changes
      regarding recovery processes and the major outcome variables. Before, during and
      after the intervention, SMS and paper-pencil questionnaires measure the same
      constructs four times a day with fewer items. We also measure blood pressure and
      collect saliva samples to map cortisol excretion across the intervention period.
      A timed experimental task (i.e., the Alternative Uses Task) is used to examine
      differences in creativity between the three groups after the intervention period.
      DISCUSSION: By combining the knowledge of work and environmental psychology about
      recovery and restorative experiences, by merging three recovery perspectives
      (settings, processes, and outcomes) and by using data triangulation, we produce
      valid results that broaden our view on mechanisms underlying recovery and enhance
      our understanding about their links to psychological, behavioural and
      physiological outcomes, resulting in a more comprehensive picture of work stress
      recovery in general. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration
      System NCT02124837. Registered 24 April 2014.

PMID- 24885179
TI  - Molecular identification of Theileria parasites of northwestern Chinese Cervidae.
AB  - BACKGROUND: Theileria and Babesia protozoan parasites are transmitted mainly by
      tick vectors. These parasites cause heavy economic losses to the live-stock
      industry, as well as affecting the health of wild animals in parasite-endemic
      areas. Identification of infectious agents in wild animals is not only crucial
      for species preservation, but also provides valuable information on parasite
      epidemiology. Here, we conducted a molecular surveillance study in Northwestern
      China to assess the prevalence of blood pathogens in cervids. METHODS: PCR
      analysis and microscopic evaluation of blood smears to detect Theileria- and
      Babesia-related diseases in Cervidae were conducted, in which 22 blood samples
      from red deer (n = 22) in Qilian Mountain and 20 from sika deer (n = 20) in Long
      Mountain were collected and tested for the presence of Theileria and Babesia. The
      18S rRNA gene was amplified, and selected polymerase chain reaction (PCR)
      positive samples were sequenced for species identification. RESULTS: PCR revealed
      that 9.1% of the Qilian Mountain samples and 20% of the Long Mountain samples
      were positive for Theileria uilenbergi; 90.09% of the Qilian Mountain samples (n
      = 22) were positive for T. capreoli, but all of the Long Mountain samples (n =
      20) were negative for T. capreoli; no other Theileria or Babesia species were
      found. PCR showed that T. uilenbergi and T. capreoli were present in red deer in
      Qilian Mountain, while only T. uilenbergi was found in sika Deer in Long
      Mountain. The 18S rRNA gene sequences were aligned against the corresponding
      GenBank sequences of known isolates of Theileria and Babesia and subjected to
      phylogenetic analysis. The phylogenetic tree showed that the newly isolated
      Theileria spp. could be classified as belonging to two clades: one group belonged
      to the same clade as T. uilenbergi, the other to a clade containing T. capreoli.
      CONCLUSIONS: Our results provide important data to increase understanding of the
      epidemiology of Cervidae theileriosis, and will assist with the implementation of
      measures to control theileriosis transmission to Cervidae and small ruminants in
      central China.

PMID- 24885180
TI  - Education and knowledge helps combating malaria, but not degedege: a cross
      sectional study in Rufiji, Tanzania.
AB  - BACKGROUND: Traditional medicine is readily available in Tanzania, and local
      terms like degedege is widely used for malaria-like illnesses, often associated
      with supernatural forces. Malaria prevention and intervention efforts can benefit
      from policy-makers' awareness of local perceptions and beliefs in the rural areas
      affected by malaria. This study measured knowledge, attitudes and behaviour
      towards malaria and malaria-like illnesses. METHODS: A cross-sectional survey was
      conducted in a rural area in Rufiji, Tanzania. A case report form employing a
      scoring system was used to capture participants' knowledge of malaria and another
      for preventive actions against malaria. Logistic regression was used to assess
      factors associated with knowledge and preventive action. RESULTS: Most of the
      participants possessed good knowledge about malaria transmission (82.1%),
      prevention (85.2%) and where to get treatment (96.4%). Fewer were familiar with
      fever (58.2%) and other common symptoms of malaria (32.7%), and even fewer
      actually put their knowledge into action. The action score measured the use of
      bed net, treatment of nets, indoor use of insecticide residual spraying (IRS),
      and proportion of households with tight windows, among the participants. As many
      as 35.7% scored zero on preventive actions, while 37.2% achieved a high action
      score. Education level and belonging to the age group 30 to 49 were significantly
      associated with higher knowledge. Education level was associated with higher
      score for preventive action (OR 2.3, CI 95% 1.2-1.4). Participants generally
      perceived degedege, a local name for an illness with convulsion, as different
      from malaria both with regards to cause and possible preventive and curative
      interventions. CONCLUSION: Respondents considered degedege to have supernatural
      causes and to need treatment by a traditional healer. This may be one reason for
      care-seeking shopping and care-seeking delay. Regarding degedege as a separate
      entity may explain why malaria is not perceived as a serious health problem in
      the area, and why little preventive actions are taken. While the elders have high
      status in the society, their lack of knowledge of malaria may impact the care
      seeking pattern of their families.

PMID- 24885181
TI  - Emergence and evolution of social self-management of Parkinson's disease: study
      protocol for a 3-year prospective cohort study.
AB  - BACKGROUND: Parkinson's disease affects facial, vocal and trunk muscles. As
      symptoms progress, facial expression becomes masked, limiting the person's
      ability to communicate emotions and intentions to others. As people with the
      disease live and reside in their homes longer, the burden of caregiving is
      unmitigated by social and emotional rewards provided by an expressive individual.
      Little is known about how adults living with Parkinson's disease manage their
      social lives and how an inability to be emotionally expressive can affect social
      connections and health. Because social networks have been shown to be crucial to
      the overall well-being of people living with chronic diseases, research is needed
      on how expressive capacity affects life trajectories and health. METHODS/DESIGN:
      The overall objective is to understand the emergence and evolution of the
      trajectories of the self-management of the social lives of people living with
      Parkinson's disease. The central hypothesis is that expressive capacity predicts
      systematic change in the pattern of social self-management and quality of life
      outcomes. The specific aims of this 3-year longitudinal study of 120 people with
      the disease and a maximum of 120 care partners are: 1) characterize social self
      management trajectories over a 3-year period; 2) estimate the degree to which
      expressive nonverbal capacity predicts the trajectory; and 3) determine the
      moderating effect of gender on the association between expressive capacity and
      change in social self-management. Each participant will be assessed 14 times to
      detect rapid and non-linear changes in social participation and management of
      social activities; social network; and social comfort, general health and well
      being. DISCUSSION: This project will provide evidence to guide the development of
      interventions for supporting social integration of those living with Parkinson's
      disease, thus leading to improved overall health. It focuses on the novel
      construct of social self-management and known factors-expressive capacity and
      gender-that contribute to stigmatization. The repeated measures design detects
      triggers of rapid changes in social and health outcomes.

PMID- 24885182
TI  - Coexistence of HBsAg and HBsAb in a difficult-to-treat chronic hepatitis B: loss
      of HBsAg with entecavir plus tenofovir combination.
AB  - BACKGROUND: Some reports have documented the coexistence of Hepatitis B surfage
      Antigen (HBsAg) and anti-HBsAg antibodies (HBsAb) in patients with chronic
      hepatitis B (CHB), often in the absence of amino acid substitutions in the HBsAg
      sequences of the Hepatitis B Virus (HBV) genome able to explain an immunological
      escape variant.HBV genome has a very compact coding organization, with four
      partially overlapping open reading frames (ORFs). Because the reverse
      transcriptase region (rt) of HBV polymerase overlaps the HBsAg ORF, it is
      possible that some mutations in the HBsAg region correspond to mutations in the
      rt ORF, conferring resistance to current antiviral therapies. This unique case
      explores the response to antiviral therapies of a CHB with concurrent HBsAg and
      HBsAb positivity, and analyse the clinical implications of possible mutations in
      rt and HBsAg ORFs. CASE PRESENTATION: Here we describe the case of a 59 year-old
      Italian man suffering from Hepatitis B envelope Antigen (HBeAg) positive CHB with
      concurrent HBsAb positivity. By ultra-deep pyro-sequencing (UDPS) technique,
      mutations conferring immunological escape or resistance to antiviral therapies
      were found neither in HBsAg nor in HBV rt ORFs, respectively. The patient was
      unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus
      entecavir combination. Surprisingly, during entecavir plus tenofovir combination,
      anti-HBe seroconversion and HBsAg loss were observed, while the titer of HBsAb
      persisted. CONCLUSIONS: Concurrent HBsAg/HBsAb positivity in active CHB is a
      clinical and virological dilemma. In this setting, there are not consistent data
      about the response to conventional therapies and the immunological balance
      between host and virus remains so far unexplained. This is, to our knowledge, the
      first case described of a CHB with HBsAg/HBsAb positivity, wild type for
      clinically relevant mutations in HBsAg and rt ORFs, successfully treated with a
      combination of nucleot(s)ide analogues (NAs).

PMID- 24885183
TI  - The effects of diet induced obesity on breast cancer associated pathways in mice
      deficient in SFRP1.
AB  - BACKGROUND: Secreted frizzled-related proteins (SFRPs) are a family of proteins
      that block the Wnt signaling pathway and loss of Sfrp1 expression is observed in
      breast cancer. The molecular mechanisms by which obesity contributes to breast
      tumorigenesis are not well defined, but involve increased inflammation. Mice
      deficient in Sfrp1 show enhanced mammary gland inflammation in response to diet
      induced obesity (DIO). Furthermore, mammary glands from Sfrp1-/- mice exhibit
      increased Wnt signaling, decreased cell death responses, and excessive hyper
      branching. The work described here was initiated to investigate whether obesity
      exacerbates the aforementioned pathways, as they each play a key roles in the
      development of breast cancer. FINDINGS: Wnt signaling is significantly affected
      by DIO and Sfrp1-/- loss as revealed by analysis of Myc mRNA expression and
      active beta-catenin protein expression. Furthermore, Sfrp1-/- mice fed a high fat
      diet (HFD) exhibit an increase in mammary cell proliferation. The death response
      is also impaired in the mammary gland of Sfrp1-/- mice fed a normal diet (ND) as
      well as a HFD. In response to gamma-irradiation, mammary glands from Sfrp1-/-
      mice express significantly less Bax and Bbc3 mRNA, caspase-3 positive cells, and
      p53 protein. The expression of Wnt4 and Tnfs11 are critical for normal
      progesterone mediated mammary gland development and in response to obesity, Sfrp1
      /- mice express significantly more Wnt4 and Tnfs11 mRNA expression. Evaluation of
      progesterone receptor (PR) expression showed that DIO increases the number of PR
      positive cells. CONCLUSIONS: Our data indicate that the expression of Sfrp1 is a
      critical factor required for maintaining appropriate cellular homeostasis in
      response to the onset of obesity.

PMID- 24885184
TI  - Corporal punishment, maternal warmth, and child adjustment: a longitudinal study
      in eight countries.
AB  - Two key tasks facing parents across cultures are managing children's behaviors
      (and misbehaviors) and conveying love and affection. Previous research has found
      that corporal punishment generally is related to worse child adjustment, whereas
      parental warmth is related to better child adjustment. This study examined
      whether the association between corporal punishment and child adjustment problems
      (anxiety and aggression) is moderated by maternal warmth in a diverse set of
      countries that vary in a number of sociodemographic and psychological ways.
      Interviews were conducted with 7- to 10-year-old children (N = 1,196; 51% girls)
      and their mothers in 8 countries: China, Colombia, Italy, Jordan, Kenya, the
      Philippines, Thailand, and the United States. Follow-up interviews were conducted
      1 and 2 years later. Corporal punishment was related to increases, and maternal
      warmth was related to decreases, in children's anxiety and aggression over time;
      however, these associations varied somewhat across groups. Maternal warmth
      moderated the effect of corporal punishment in some countries, with increases in
      anxiety over time for children whose mothers were high in both warmth and
      corporal punishment. The findings illustrate the overall association between
      corporal punishment and child anxiety and aggression as well as patterns specific
      to particular countries. Results suggest that clinicians across countries should
      advise parents against using corporal punishment, even in the context of parent
      child relationships that are otherwise warm, and should assist parents in finding
      other ways to manage children's behaviors. 

PMID- 24885186
TI  - Technical considerations for genotyping multi-allelic copy number variation
      (CNV), in regions of segmental duplication.
AB  - BACKGROUND: Intrachromosomal segmental duplications provide the substrate for non
      allelic homologous recombination, facilitating extensive copy number variation in
      the human genome. Many multi-copy gene families are embedded within genomic
      regions with high levels of sequence identity (>95%) and therefore pose
      considerable analytical challenges. In some cases, the complexity involved in
      analyzing such regions is largely underestimated. Rapid, cost effective analysis
      of multi-copy gene regions have typically implemented quantitative approaches,
      however quantitative data are not an absolute means of certainty. Therefore any
      technique prone to degrees of measurement error can produce ambiguous results
      that may lead to spurious associations with complex disease. RESULTS: In this
      study we have focused on testing the accuracy and reproducibility of quantitative
      analysis techniques. With reference to the C-C Chemokine Ligand-3-like-1 (CCL3L1)
      gene, we performed analysis using real-time Quantitative PCR (QPCR), Multiplex
      Ligation-dependent Probe Amplification (MLPA) and Paralogue Ratio Test (PRT).
      After controlling for potential outside variables on assay performance, including
      DNA concentration, quality, preparation and storage conditions, we find that real
      time QPCR produces data that does not cluster tightly around copy number integer
      values, with variation substantially greater than that of the MLPA or PRT
      systems. We find that the method of rounding real-time QPCR measurements can
      potentially lead to mis-scoring of copy number genotypes and suggest caution
      should be exercised in interpreting QPCR data. CONCLUSIONS: We conclude that real
      time QPCR is inherently prone to measurement error, even under conditions that
      would seem favorable for association studies. Our results indicate that potential
      variability in the physicochemical properties of the DNA samples cannot solely
      explain the poor performance exhibited by the real-time QPCR systems. We
      recommend that more robust approaches such as PRT or MLPA should be used to
      genotype multi-allelic copy number variation in disease association studies and
      suggest several approaches which can be implemented to ensure the quality of the
      copy number typing using quantitative methods.

PMID- 24885185
TI  - Alternative splicing and nonsense-mediated decay of circadian clock genes under
      environmental stress conditions in Arabidopsis.
AB  - BACKGROUND: The circadian clock enables living organisms to anticipate recurring
      daily and seasonal fluctuations in their growth habitats and synchronize their
      biology to the environmental cycle. The plant circadian clock consists of
      multiple transcription-translation feedback loops that are entrained by
      environmental signals, such as light and temperature. In recent years,
      alternative splicing emerges as an important molecular mechanism that modulates
      the clock function in plants. Several clock genes are known to undergo
      alternative splicing in response to changes in environmental conditions,
      suggesting that the clock function is intimately associated with environmental
      responses via the alternative splicing of the clock genes. However, the
      alternative splicing events of the clock genes have not been studied at the
      molecular level. RESULTS: We systematically examined whether major clock genes
      undergo alternative splicing under various environmental conditions in
      Arabidopsis. We also investigated the fates of the RNA splice variants of the
      clock genes. It was found that the clock genes, including EARLY FLOWERING 3
      (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative
      splicing, undergo extensive alternative splicing through diverse modes of
      splicing events, such as intron retention, exon skipping, and selection of
      alternative 5' splice site. Their alternative splicing patterns were
      differentially influenced by changes in photoperiod, temperature extremes, and
      salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1
      (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway,
      whereas those of other clock genes were insensitive to NMD. CONCLUSION: Taken
      together, our observations demonstrate that the major clock genes examined
      undergo extensive alternative splicing under various environmental conditions,
      suggesting that alternative splicing is a molecular scheme that underlies the
      linkage between the clock and environmental stress adaptation in plants. It is
      also envisioned that alternative splicing of the clock genes plays more complex
      roles than previously expected.

PMID- 24885187
TI  - Quantitative measurements of HER2 and phospho-HER2 expression: correlation with
      pathologic response to neoadjuvant chemotherapy and trastuzumab.
AB  - BACKGROUND: Preoperative therapy with chemotherapy and the HER2-targeted
      monoclonal antibody trastuzumab is valuable for patients with large or locally
      advanced HER2-positive (HER2+) breast cancers but traditional methods of
      measuring HER2 expression do not accurately stratify patients for likelihood of
      response. Quantitative immunofluorescent approaches have the potential to provide
      a mathematically continuous measure of HER2. Here we seek to determine whether
      quantitative measurement of HER2 or phospho-HER2 correlates with likelihood of
      response to trastuzumab- containing neoadjuvant therapy. METHODS: We evaluated
      core biopsy samples from 27 HER2+ breast cancer patients enrolled in a
      preoperative clinical trial using trastuzumab, nab-paclitaxel and carboplatin
      combination therapy (BrUOG BR-211B (NCT00617942)). Tumor core biopsies were taken
      before initiation of treatment and 9-13 days after patients received "run-in"
      doses of either single agent trastuzumab or nab-paclitaxel. The AQUA method of
      quantitative immunofluorescence was used for analysis of in situ protein
      expression. Patients then received 18 weeks of treatment, followed by surgery to
      assess pathologic response to the neoadjuvant regimen. RESULTS: A HER2 score of
      2111 by AQUA analysis has been shown to be equivalent to HER2 3+ by
      immunohistochemical staining in previous studies. Of 20 evaluable patients, 10
      cases who achieved a pathologic complete response (pathCR) with neoadjuvant
      treatment had a mean HER2 level of 10251 compared with 4766 in the patients
      without pathCR (p = 0.0021). Measurement of phospho-HER2 showed no difference in
      pathCR vs non-pathCR groups. In 9 patients who had HER2 levels repeated after a
      single treatment with trastuzumab there was no evidence of a reduction in the
      HER2 or phospho-HER2 levels following that exposure. CONCLUSIONS: High levels of
      HER2 are associated with achievement of a pathCR in the preoperative setting,
      while levels of Phospho-HER2 were not predictive of response. This data suggests
      that accurate measurement of HER2 may help determine the likelihood of response
      in the pre-surgical setting. Further validation in larger cohorts is required,
      but this pilot data shows the feasibility of this approach.

PMID- 24885188
TI  - Daily activity during stability and exacerbation of chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: During most COPD exacerbations, patients continue to live in the
      community but there is little information on changes in activity during
      exacerbations due to the difficulties of obtaining recent, prospective baseline
      data. METHODS: Patients recorded on daily diary cards any worsening in
      respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken
      per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined
      by increased respiratory symptoms and the number of exacerbations experienced in
      the 12 months preceding the recording of daily step count used to divide patients
      into frequent (> = 2/year) or infrequent exacerbators. RESULTS: The 73 COPD
      patients (88% male) had a mean (+/-SD) age 71(+/-8) years and FEV1 53(+/-16)%
      predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At
      exacerbation onset, symptom count rose by 1.9(+/-1.3) and PEF fell by 7(+/-13)
      l/min. Mean daily step count fell from 4154(+/-2586) steps/day during a preceding
      baseline week to 3673(+/-2258) step/day during the initial 7 days of exacerbation
      (p = 0.045). Patients with larger falls in activity at exacerbation took longer
      to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count
      was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p <
      0.001). Recovery in step count was also faster in untreated compared to treated
      exacerbation (p = 0.030).Daily step count fell faster over time in the 40
      frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33
      infrequent exacerbators (p = 0.002). CONCLUSIONS: COPD exacerbations reduced
      physical activity and frequent exacerbations accelerate decline in activity over
      time.

PMID- 24885190
TI  - Effect of seasonality on the estimated mean value of nutrients and ranking
      ability of a self-administered diet history questionnaire.
AB  - BACKGROUND: We examined the effect of seasonality on the validity (ability to
      estimate the mean intake of a group and ranking ability) of nutrient intakes
      estimated with a comprehensive self-administered diet history questionnaire (DHQ)
      developed for the assessment of Japanese diets during the preceding one month,
      using semi-weighed dietary records (DRs) as a reference method. METHODS: This
      study was conducted in three areas in Japan (Osaka, Nagano, and Tottori). The
      study population included 92 Japanese men aged 32-76 years and 92 Japanese women
      aged 31-69 years (30 from Osaka, 31 from Nagano, and 31 from Tottori for each
      sex). A DHQ and a four-day DR were completed four times at 3-month intervals,
      once per season. The effect of seasonality was examined by the level of agreement
      among seasons using mean nutrient intake and correlation coefficients. RESULTS:
      Significant differences in estimated energy-adjusted intakes of 42 selected
      nutrients between the average of DRs administered 16 times throughout a year and
      that of the DHQ administered four times in each season (fall, winter, spring, and
      summer) were observed for 30, 29, 30, and 31 nutrients for men and 21, 28, 30,
      and 31 nutrients for women, respectively. Pearson correlation coefficients
      between the DRs and the DHQs for energy-adjusted intakes of the 42 nutrients
      showed significant inter-season differences in 11 nutrients for men and 13
      nutrients for women. Particularly, correlation coefficients of fat,
      monounsaturated fat, polyunsaturated fat, n-6 polyunsaturated fat, alpha
      linolenic acid, and cholesterol in spring and cryptoxanthin in summer for men,
      and fat, saturated fat, and monounsaturated fat in spring and summer and thiamin
      and iron in summer for women were markedly altered by seasonality. CONCLUSIONS:
      Mean nutrient intake estimated by the DHQ varied by season, indicating that any
      consideration of nutrient intake estimated by the DHQ as a yearly average intake
      may be problematic. In contrast, the effect of seasonality on the ranking ability
      of the DHQ was relatively small, and thus the use of a DHQ to rank individuals by
      nutrient intake is acceptable for epidemiological studies, regardless of season.

PMID- 24885189
TI  - Transcriptomic and metabolomic analysis of copper stress acclimation in
      Ectocarpus siliculosus highlights signaling and tolerance mechanisms in brown
      algae.
AB  - BACKGROUND: Brown algae are sessile macro-organisms of great ecological relevance
      in coastal ecosystems. They evolved independently from land plants and other
      multicellular lineages, and therefore hold several original ontogenic and
      metabolic features. Most brown algae grow along the coastal zone where they face
      frequent environmental changes, including exposure to toxic levels of heavy
      metals such as copper (Cu). RESULTS: We carried out large-scale transcriptomic
      and metabolomic analyses to decipher the short-term acclimation of the brown
      algal model E. siliculosus to Cu stress, and compared these data to results known
      for other abiotic stressors. This comparison demonstrates that Cu induces
      oxidative stress in E. siliculosus as illustrated by the transcriptomic overlap
      between Cu and H2O2 treatments. The common response to Cu and H2O2 consisted in
      the activation of the oxylipin and the repression of inositol signaling pathways,
      together with the regulation of genes coding for several transcription-associated
      proteins. Concomitantly, Cu stress specifically activated a set of genes coding
      for orthologs of ABC transporters, a P1B-type ATPase, ROS detoxification systems
      such as a vanadium-dependent bromoperoxidase, and induced an increase of free
      fatty acid contents. Finally we observed, as a common abiotic stress mechanism,
      the activation of autophagic processes on one hand and the repression of genes
      involved in nitrogen assimilation on the other hand. CONCLUSIONS: Comparisons
      with data from green plants indicate that some processes involved in Cu and
      oxidative stress response are conserved across these two distant lineages. At the
      same time the high number of yet uncharacterized brown alga-specific genes
      induced in response to copper stress underlines the potential to discover new
      components and molecular interactions unique to these organisms. Of particular
      interest for future research is the potential cross-talk between reactive oxygen
      species (ROS)-, myo-inositol-, and oxylipin signaling.

PMID- 24885191
TI  - DNA-encoded nucleosome occupancy is associated with transcription levels in the
      human malaria parasite Plasmodium falciparum.
AB  - BACKGROUND: In eukaryotic organisms, packaging of DNA into nucleosomes controls
      gene expression by regulating access of the promoter to transcription factors.
      The human malaria parasite Plasmodium falciparum encodes relatively few
      transcription factors, while extensive nucleosome remodeling occurs during its
      replicative cycle in red blood cells. These observations point towards an
      important role of the nucleosome landscape in regulating gene expression.
      However, the relation between nucleosome positioning and transcriptional activity
      has thus far not been explored in detail in the parasite. RESULTS: Here, we
      analyzed nucleosome positioning in the asexual and sexual stages of the
      parasite's erythrocytic cycle using chromatin immunoprecipitation of MNase
      digested chromatin, followed by next-generation sequencing. We observed a
      relatively open chromatin structure at the trophozoite and gametocyte stages,
      consistent with high levels of transcriptional activity in these stages.
      Nucleosome occupancy of genes and promoter regions were subsequently compared to
      steady-state mRNA expression levels. Transcript abundance showed a strong inverse
      correlation with nucleosome occupancy levels in promoter regions. In addition, AT
      repeat sequences were strongly unfavorable for nucleosome binding in P.
      falciparum, and were overrepresented in promoters of highly expressed genes.
      CONCLUSIONS: The connection between chromatin structure and gene expression in P.
      falciparum shares similarities with other eukaryotes. However, the remarkable
      nucleosome dynamics during the erythrocytic stages and the absence of a large
      variety of transcription factors may indicate that nucleosome binding and
      remodeling are critical regulators of transcript levels. Moreover, the strong
      dependency between chromatin structure and DNA sequence suggests that the P.
      falciparum genome may have been shaped by nucleosome binding preferences.
      Nucleosome remodeling mechanisms in this deadly parasite could thus provide
      potent novel anti-malarial targets.

PMID- 24885192
TI  - Safety relevant knowledge of orally anticoagulated patients without self
      monitoring: a baseline survey in primary care.
AB  - BACKGROUND: Effective and safe management of oral anticoagulant treatment (OAT)
      requires a high level of patient knowledge and adherence. The aim of this study
      was to assess patient knowledge about OAT and factors associated with patient
      knowledge. METHODS: This is a baseline survey of a cluster-randomized controlled
      trial in 22 general practices with an educational intervention for patients or
      their caregivers. We assessed knowledge about general information on OAT and key
      facts regarding nutrition, drug-interactions and other safety precautions of 345
      patients at baseline. RESULTS: Participants rated their knowledge about OAT as
      excellent to good (56%), moderate (36%) or poor (8%). However, there was a
      discrepancy between self-rated knowledge and evaluated actual knowledge and we
      observed serious knowledge gaps. Half of the participants (49%) were unaware of
      dietary recommendations. The majority (80%) did not know which non-prescription
      analgesic is the safest and 73% indicated they would not inform pharmacists about
      OAT. Many participants (35-75%) would not recognize important emergency
      situations. After adjustment in a multivariate analysis, older age and less than
      10 years education remained significantly associated with lower overall score,
      but not with self-rated knowledge. CONCLUSIONS: Patients have relevant knowledge
      gaps, potentially affecting safe and effective OAT. There is a need to assess
      patient knowledge and for structured education programs. TRIAL REGISTRATION:
      Deutsches Register Klinischer Studien (German Clinical Trials Register):
      DRKS00000586.Universal Trial Number (UTN U1111-1118-3464).

PMID- 24885193
TI  - FIGG: simulating populations of whole genome sequences for heterogeneous data
      analyses.
AB  - BACKGROUND: High-throughput sequencing has become one of the primary tools for
      investigation of the molecular basis of disease. The increasing use of sequencing
      in investigations that aim to understand both individuals and populations is
      challenging our ability to develop analysis tools that scale with the data. This
      issue is of particular concern in studies that exhibit a wide degree of
      heterogeneity or deviation from the standard reference genome. The advent of
      population scale sequencing studies requires analysis tools that are developed
      and tested against matching quantities of heterogeneous data. RESULTS: We
      developed a large-scale whole genome simulation tool, FIGG, which generates large
      numbers of whole genomes with known sequence characteristics based on direct
      sampling of experimentally known or theorized variations. For normal variations
      we used publicly available data to determine the frequency of different mutation
      classes across the genome. FIGG then uses this information as a background to
      generate new sequences from a parent sequence with matching frequencies, but
      different actual mutations. The background can be normal variations, known
      disease variations, or a theoretical frequency distribution of variations.
      CONCLUSION: In order to enable the creation of large numbers of genomes, FIGG
      generates simulated sequences from known genomic variation and iteratively
      mutates each genome separately. The result is multiple whole genome sequences
      with unique variations that can primarily be used to provide different reference
      genomes, model heterogeneous populations, and can offer a standard test
      environment for new analysis algorithms or bioinformatics tools.

PMID- 24885196
TI  - Surface morphology and properties of ternary polymer blends: effect of the
      migration of minor components.
AB  - In this work, the surface morphology and properties of ternary polymer blends and
      the migration of minor component molecules to the top surface layer of the films
      were studied. We used polystyrene (PS), poly(butylene adipate-co-terephthalate),
      polycaprolactone, poly(methyl methacrylate), and polylactide as second minor
      phases in a blend of polyethylene terephthalate-poly(ethylene glycol) (PET-PEG).
      The morphology of the ternary systems predicted using the spreading coefficient
      and relative interfacial energy concepts was confirmed by scanning electron
      microscopy images. The surface characterization results showed a higher rate of
      migration of PEG to the polymer-air interface in the systems with a nonwetting
      morphology and the highest in the PET-PS-PEG blend. Atomic force microscopy
      images suggested that the high surface hydrophilicity of the PET-PS-PEG blend is
      due to a dendritic pattern of PEG crystals on the film surface, which were not
      observed for the other samples. 

PMID- 24885194
TI  - Ubiquitin ligase Cbl-b represses IGF-I-induced epithelial mesenchymal transition
      via ZEB2 and microRNA-200c regulation in gastric cancer cells.
AB  - BACKGROUND: Insulin-like growth factor I (IGF-I) can induce epithelial
      mesenchymal transition (EMT) in many epithelial tumors; however, the molecular
      mechanism by which this occurs is not clearly understood. Additionally, little is
      known about the involvement of IGF-I in gastric cancer. METHODS: Two gastric
      cancer cell lines were treated with IGF-I to induce EMT and levels of
      transcription factor ZEB2 and microRNA-200c (miR-200c) were measured. Cells were
      treated with Akt/ERK inhibitors to investigate the role of these pathways in IGF
      I-mediated EMT. Transfection of shRNA plasmids was used to silence the ubiquitin
      ligase Cbl-b to assess its involvement in this process. The relationship between
      IGF-IR and Cbl-b expression, and the effect of IGF-IR and Cbl-b on metastasis
      were analyzed in primary gastric adenocarcinoma patients. RESULTS: IGF-I-induced
      gastric cancer cell EMT was accompanied by ZEB2 up-regulation. Furthermore, both
      Akt/ERK inhibitors and knockdown of Akt/ERK gene reversed IGF-I-induced ZEB2 up
      regulation and EMT through up-regulation of miR-200c, suggesting the involvement
      of an Akt/ERK-miR-200c-ZEB2 axis in IGF-I-induced EMT. The ubiquitin ligase Cbl-b
      also ubiquitinated and degraded IGF-IR and inhibited the Akt/ERK-miR-200c-ZEB2
      axis, leading to the repression of IGF-I-induced EMT. There was a significant
      negative correlation between the expression of IGF-IR and Cbl-b in gastric cancer
      patient tissues (r = -0.265, p < 0.05). More of patients with IGF-IR-positive
      expression and Cbl-b-negative expression were with lymph node metastasis (p <
      0.001). CONCLUSIONS: Together, these findings demonstrate that the ubiquitin
      ligase Cbl-b represses IGF-I-induced EMT, likely through targeting IGF-IR for
      degradation and further inhibiting the Akt/ERK-miR-200c-ZEB2 axis in gastric
      cancer cells.

PMID- 24885195
TI  - Reduced expression of ezrin in urothelial bladder cancer signifies more advanced
      tumours and an impaired survival: validatory study of two independent patient
      cohorts.
AB  - BACKGROUND: Reduced membranous expression of the cytoskeleton-associated protein
      ezrin has previously been demonstrated to correlate with tumour progression and
      poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder
      treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the
      associations with adverse clinicopathological factors have been validated in
      another, unselected, cohort (n = 104). In the present study, we examined the
      prognostic significance of ezrin expression in urothelial bladder cancer in a
      total number of 442 tumours from two independent patient cohorts. METHODS:
      Immunohistochemical expression of ezrin was evaluated in tissue microarrays with
      tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and
      one population-based cohort (n = 342; cohort II). Classification regression tree
      analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis,
      log rank test and Cox regression proportional hazards' modeling were used to
      evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific
      survival (DSS) and progression-free survival (PFS). RESULTS: Ezrin expression
      could be evaluated in tumours from 100 and 342 cases, respectively. In both
      cohorts, reduced membranous ezrin expression was significantly associated with
      more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p
      = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p
      < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a
      significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and
      HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31).
      This association also remained significant in adjusted analysis in Cohort I
      (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort
      II, there was no significant association between ezrin expression and time to
      progression. CONCLUSIONS: The results from this study validate previous findings
      of reduced membranous ezrin expression in urothelial bladder cancer being
      associated with unfavourable clinicopathological characteristics and an impaired
      survival. The utility of ezrin as a prognostic biomarker in transurethral
      resection specimens merits further investigation.

PMID- 24885197
TI  - A robotic test of proprioception within the hemiparetic arm post-stroke.
AB  - BACKGROUND: Proprioception plays important roles in planning and control of limb
      posture and movement. The impact of proprioceptive deficits on motor function
      post-stroke has been difficult to elucidate due to limitations in current tests
      of arm proprioception. Common clinical tests only provide ordinal assessment of
      proprioceptive integrity (eg. intact, impaired or absent). We introduce a
      standardized, quantitative method for evaluating proprioception within the arm on
      a continuous, ratio scale. We demonstrate the approach, which is based on signal
      detection theory of sensory psychophysics, in two tasks used to characterize
      motor function after stroke. METHODS: Hemiparetic stroke survivors and
      neurologically intact participants attempted to detect displacement- or force
      perturbations robotically applied to their arm in a two-interval, two-alternative
      forced-choice test. A logistic psychometric function parameterized detection of
      limb perturbations. The shape of this function is determined by two parameters:
      one corresponds to a signal detection threshold and the other to variability of
      responses about that threshold. These two parameters define a space in which
      proprioceptive sensation post-stroke can be compared to that of neurologically
      intact people. We used an auditory tone discrimination task to control for
      potential comprehension, attention and memory deficits. RESULTS: All but one
      stroke survivor demonstrated competence in performing two-alternative
      discrimination in the auditory training test. For the remaining stroke survivors,
      those with clinically identified proprioceptive deficits in the hemiparetic arm
      or hand had higher detection thresholds and exhibited greater response
      variability than individuals without proprioceptive deficits. We then identified
      a normative parameter space determined by the threshold and response variability
      data collected from neurologically intact participants. By plotting displacement
      detection performance within this normative space, stroke survivors with and
      without intact proprioception could be discriminated on a continuous scale that
      was sensitive to small performance variations, e.g. practice effects across days.
      CONCLUSIONS: The proposed method uses robotic perturbations similar to those used
      in ongoing studies of motor function post-stroke. The approach is sensitive to
      small changes in the proprioceptive detection of hand motions. We expect this new
      robotic assessment will empower future studies to characterize how proprioceptive
      deficits compromise limb posture and movement control in stroke survivors.

PMID- 24885198
TI  - Mode conversion in high-definition plasmonic optical nanocircuits.
AB  - Symmetric and antisymmetric guided modes on a plasmonic two-wire transmission
      line have distinct properties and are suitable for different circuit functions.
      Being able to locally convert the guided modes is important for realizing
      multifunctional optical nanocircuits. Here, we experimentally demonstrate
      successful local conversion between the symmetric and the antisymmetric modes in
      a single-crystalline gold plasmonic nanocircuit with an optimally designed mode
      converter for optical signals at 194.2 THz. Mode conversion may find applications
      in controlling nanoscale light-matter interaction. 

PMID- 24885199
TI  - Plumage condition in laying hens: genetic parameters for direct and indirect
      effects in two purebred layer lines.
AB  - BACKGROUND: Feather pecking is a major welfare issue in laying hen industry that
      leads to mortality. Due to a ban on conventional cages in the EU and on beak
      trimming in some countries of the EU, feather pecking will become an even bigger
      problem. Its severity depends both on the victim receiving pecking and on its
      group mates inflicting pecking (indirect effects), which together determine
      plumage condition of the victim. Plumage condition may depend, therefore, on both
      the direct genetic effect of an individual itself and on the indirect genetic
      effects of its group mates. Here, we present estimated genetic parameters for
      direct and indirect effects on plumage condition of different body regions in two
      purebred layer lines, and estimates of genetic correlations between body regions.
      METHODS: Feather condition scores (FCS) were recorded at 40 weeks of age for
      neck, back, rump and belly and these four scores were added-up into a total FCS.
      A classical animal model and a direct-indirect effects model were used to
      estimate genetic parameters for FCS. In addition, a bivariate model with
      mortality (0/1) was used to account for mortality before recording FCS. Due to
      mortality during the first 23 weeks of laying, 5363 (for W1) and 5089 (for WB)
      FCS records were available. RESULTS: Total heritable variance for FCS ranged from
      1.5% to 9.8% and from 9.8% to 53.6% when estimated respectively with the
      classical animal and the direct-indirect effects model. The direct-indirect
      effects model had a significantly higher likelihood. In both lines, 70% to 94% of
      the estimated total heritable variation in FCS was due to indirect effects. Using
      bivariate analysis of FCS and mortality did not affect estimates of genetic
      parameters. Genetic correlations were high between adjacent regions for FCS on
      neck, back, and rump but moderate to low for belly with other regions.
      CONCLUSION: Our results show that 70% to 94% of the heritable variation in FCS
      relates to indirect effects, indicating that methods of genetic selection that
      include indirect genetic effects offer perspectives to improve plumage condition
      in laying hens. This, in turn could reduce a major welfare problem.

PMID- 24885200
TI  - Development of an in vitro model of acquired resistance to toceranib phosphate
      (Palladia(r)) in canine mast cell tumor.
AB  - BACKGROUND: Mast cell tumors (MCTs) are the most common skin tumors in dogs and
      exhibit variable biologic behavior. Mutations in the c-kit proto-oncogene are
      associated with the tumorigenesis of MCTs, resulting in growth factor-independent
      and constitutive phosphorylation of the KIT receptor tyrosine kinase (RTK).
      Toceranib (TOC) phosphate (Palladia(r)) is a KIT RTK inhibitor that has
      biological activity against MCTs. Despite these benefits, patients ultimately
      develop resistance to TOC. Therefore, there is a need to identify distinguishing
      clinical and molecular features of resistance in this population. RESULTS: The
      canine C2 mastocytoma cell line contains an activating mutation in c-kit. Three
      TOC-resistant C2 sublines (TR1, TR2, TR3) were established over seven months by
      growing cells in increasing concentrations of TOC. TOC inhibited KIT
      phosphorylation and cell proliferation in a dose-dependent manner in the
      treatment-naive, parental C2 line (IC50 < 10 nM). In contrast, the three sublines
      were resistant to growth inhibition by TOC (IC50 > 1,000 nM) and phosphorylation
      of the KIT receptor was less inhibited compared to the TOC-sensitive C2 cells.
      Interestingly, sensitivity to three structurally distinct KIT RTK inhibitors was
      variable among the sublines, and all 3 sublines retained sensitivity to the
      cytotoxic agents vinblastine and lomustine. Sequencing of c-kit revealed
      secondary mutations in the juxtamembrane and tyrosine kinase domains of the
      resistant sublines. These included point mutations in TR1 (Q574R, M835T), TR2
      (K724R), and TR3 (K580R, R584G, A620S). Additionally, chronic TOC exposure
      resulted in c-kit mRNA and KIT protein overexpression in the TOC-resistant
      sublines compared to the parental line. C2, TR1, TR2, and TR3 cells demonstrated
      minimal P-glycoprotein (P-gp) activity and no functional P-gp. CONCLUSIONS: This
      study demonstrates the development of an in vitro model of acquired resistance to
      targeted therapy in canine MCTs harboring a c-kit-activating mutation. This model
      may be used to investigate the molecular basis of and strategies to overcome TOC
      resistance.

PMID- 24885202
TI  - Mental time travel for self and other in three- and four-year-old children.
AB  - Humans possess the unique ability to mentally travel backward in time to re
      experience past events (i.e., episodic memory) and forward in time to pre
      experience future events (i.e., episodic foresight). Although originally viewed
      as different cognitive skills, they are now both viewed as components of the
      episodic memory system. Recently, it has been suggested that the episodic system
      may allow us to not only pre-experience and predict our own future but also that
      of another person. In the current study, we investigate this possibility by
      examining the ability of three- and four-year-old children to plan for their own
      future and for that of another person. We found that both three- and four-year
      old children performed equally, when planning for their own future or when
      planning for the experimenter's future. These data are consistent with the
      finding that planning for someone else's future recruits the same neural
      structures that are used when planning for one's own future. 

PMID- 24885201
TI  - Vitamin D3 and gargling for the prevention of upper respiratory tract infections:
      a randomized controlled trial.
AB  - BACKGROUND: We undertook a 2X2 factorial, randomized controlled trial (RCT) to
      assess whether vitamin D3 supplementation (10,000 international units per week)
      versus placebo and gargling versus no gargling could prevent viral, clinical
      upper respiratory tract infection (URTI) in university students. METHODS: We
      randomized 600 students into 4 treatment arms: 1) vitamin D3 and gargling, 2)
      placebo and gargling, 3) vitamin D3 and no gargling, and 4) placebo and no
      gargling. Students completed weekly electronic surveys and submitted self
      collected mid-turbinate nasal flocked swabs during September and October in 2010
      or 2011. Symptomatic students also completed an electronic symptom diary. The
      primary and secondary outcomes were the occurrence of symptomatic clinical URTI
      and laboratory confirmed URTI respectively. RESULTS: Of 600 participants, 471
      (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%)
      reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D3
      reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79,
      CI95:0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to
      gargling reported clinical URTI compared to 65 participants (21.7%) randomized to
      the no gargling arm (RR:1.3, CI95:0.92-1.57, p = 0.19). Laboratory testing
      identified 70 infections (46.7 per 100 URTIs). Vitamin D3 treatment was
      associated with a significantly lower risk for laboratory confirmed URTI (RR:
      0.54, CI95:0.34-0.84, p = 0.007) and with a significantly lower mean viral load
      measured as log10 viral copies/mL (mean difference: -0.89, CI95: -1.7, -0.06, p =
      0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI,
      however this was not statistically significant (RR:0.82, CI95:0.53-1.26, p =
      0.36). CONCLUSIONS: These results suggest that vitamin D3 is a promising
      intervention for the prevention of URTI. Vitamin D3 significantly reduced the
      risk of laboratory confirmed URTI and may reduce the risk of clinical infections.
      TRIAL REGISTRATION:  CLINICAL TRIALS REGISTRATION: NCT01158560.

PMID- 24885203
TI  - A decrease in aquaporin 2 excretion is associated with bed rest induced high
      calciuria.
AB  - BACKGROUND: Exposure to microgravity or immobilization results in alterations of
      renal function, fluid redistribution and bone loss, which couples to a rise of
      urinary calcium excretion. We recently demonstrated that high calcium delivery to
      the collecting duct reduces local Aquaporin-2 (AQP2) mediated water reabsorption
      under vasopressin action, thus limiting the maximal urinary concentration and
      reducing calcium saturation. To investigate renal water balance adaptation during
      bed rest, a model to mimic the effects of microgravity on earth, the effect of
      changes in urinary calcium on urinary AQP2 excretion were assessed. METHODS: Ten
      healthy men (aged 21-28 years) participated in the experiment. Study design
      included 7 days of adaptation and 35 days of continuous bed rest (days -6 to 0
      and 1 to 35, respectively) under controlled diet. Food records and 24-hour urine
      samples were collected daily from day -3 to 35. Changes in blood hematocrit were
      used as an indirect index of plasma volume changes. AQP2 excretion was measured
      by ELISA. RESULTS: Bed rest induced bone demineralization and a transient
      increase in urinary calcium followed by transient decrease in AQP2 excretion,
      which can reduce the urine concentrating ability causing plasma volume reduction.
      The return of calciuria to baseline was followed by a recovery of AQP2 excretion,
      which allows for a partial restoration of plasma volume. CONCLUSIONS: These
      results further support the view that urinary calcium can modulate the
      vasopressin-dependent urine concentration through a down-regulation of AQP2
      expression/trafficking. This mechanism could have a key role in the prevention of
      urine super-saturation due to hypercalciuria.

PMID- 24885204
TI  - UK medical tourists in Thailand: they are not who you think they are.
AB  - BACKGROUND: Travel for medical treatment is an aspect of globalization and health
      that is comparatively less understood. Little is known about volume,
      characteristic and motivation of medical tourists, limiting understanding of
      effects on health systems and patients. Thailand is amongst a handful of
      countries that have positioned themselves as medical tourism destination. This
      paper examines in unprecedented detail volume and characteristics of medical
      tourists who travel from the UK to Thailand for treatment. METHODS: As part of a
      wider medical tourism study, authors gained access to over 4000 patient records
      from the five largest private hospitals in Thailand. These included information
      on country of origin, gender, age, arrival month, hospitalization, diagnosis,
      procedures, length of stay, medical expenditure and type of payment. Patient
      records were analysed to understand who travels and findings were triangulated
      with data from the UK International Passenger Survey (IPS). RESULTS: 104,830
      medical tourists visited these hospitals in Thailand in 2010. While patients
      originate all over the world, UK medical tourists represent the largest group
      amongst Europeans. The majority UK medical tourists (60%) have comparatively
      small, elective procedures, costing less than USD 500. A significant minority of
      patients travel for more serious orthopedic and cardiothoracic procedures. Data
      of individual patient records from Thailand shows a higher number of UK patients
      traveled to Thailand than indicated by the IPS. CONCLUSIONS: Thailand is
      attracting a large number of medical tourists including larger numbers of UK
      patients than previously estimated. However, as many patients travel for
      comparatively minor procedures treatment may not be their primary motivation for
      travel. The small but significant proportion of older UK residents traveling for
      complex procedures may point to challenges within the NHS.

PMID- 24885205
TI  - Correlation of survival and EGFR mutation with predominant histologic subtype
      according to the new lung adenocarcinoma classification in stage IB patients.
AB  - BACKGROUND: A new lung adenocarcinoma classification proposed by the
      International Association for the Study of Lung Cancer, American Thoracic
      Society, and European Respiratory Society (IASLC/ATS/ERS) has recently been
      published. This study aimed to investigate the utility of the new histological
      classification for identifying the prognostic subtypes of adenocarcinomas in
      stage IB patients.Correlations between the classification and the presence of
      epidermal growth factor receptor (EGFR) mutation status was also studied.
      METHODS: One hundred and thirty-six patients with stage IB lung adenocarcinoma
      operated on in Zhejiang Cancer Hospital were identified between 2002 and 2011.
      Patients overall survival and disease-free survival were calculated using Kaplan
      Meier and Cox regression analyses. EGFR mutations were detected using the
      amplification refractory mutation system. RESULTS: A total of 136 cases were
      included in current study, of which 38 were papillary predominant, 39 were acinar
      predominant, 22 were micropapillary predominant, 21 were lepidic predominant
      subtypes, 14 were solid predominant, and 2 were variants of invasive
      adenocarcinoma. Patients with micropapillary- and solid-predominant tumors had
      the lowest five-year disease-free survival (28.4 and 36.7%, respectively).
      Univariate and multivariate analysis showed that the micropapillary-predominant
      subtype was an independent predictor of disease-free survival (P = 0.0041 and
      0.048, respectively), but not overall survival (P = 0.175 and 0.214,
      respectively). EGFR mutations were significantly associated with the
      micropapillary-predominant subtype patients (P = 0.0026). The EGFR mutation
      frequency is lower in the solid-predominant subtype than other subtypes (P =
      0.0508). CONCLUSIONS: The predominant subtype in the primary tumor was associated
      with prognosis in resected stage IB lung adenocarcinoma. The EGFR mutation
      frequency of micropapillary-predominant subtype is higher than other subtypes.

PMID- 24885206
TI  - A lab-on-chip for malaria diagnosis and surveillance.
AB  - BACKGROUND: Access to timely and accurate diagnostic tests has a significant
      impact in the management of diseases of global concern such as malaria. While
      molecular diagnostics satisfy this need effectively in developed countries,
      barriers in technology, reagent storage, cost and expertise have hampered the
      introduction of these methods in developing countries. In this study a simple,
      lab-on-chip PCR diagnostic was created for malaria that overcomes these
      challenges. METHODS: The platform consists of a disposable plastic chip and a low
      cost, portable, real-time PCR machine. The chip contains a desiccated hydrogel
      with reagents needed for Plasmodium specific PCR. Chips can be stored at room
      temperature and used on demand by rehydrating the gel with unprocessed blood,
      avoiding the need for sample preparation. These chips were run on a custom-built
      instrument containing a Peltier element for thermal cycling and a laser/camera
      setup for amplicon detection. RESULTS: This diagnostic was capable of detecting
      all Plasmodium species with a limit of detection for Plasmodium falciparum of 2
      parasites/MUL of blood. This exceeds the sensitivity of microscopy, the current
      standard for diagnosis in the field, by ten to fifty-fold. In a blind panel of
      188 patient samples from a hyper-endemic region of malaria transmission in
      Uganda, the diagnostic had high sensitivity (97.4%) and specificity (93.8%)
      versus conventional real-time PCR. The test also distinguished the two most
      prevalent malaria species in mixed infections, P. falciparum and Plasmodium
      vivax. A second blind panel of 38 patient samples was tested on a streamlined
      instrument with LED-based excitation, achieving a sensitivity of 96.7% and a
      specificity of 100%. CONCLUSIONS: These results describe the development of a lab
      on-chip PCR diagnostic from initial concept to ready-for-manufacture design. This
      platform will be useful in front-line malaria diagnosis, elimination programmes,
      and clinical trials. Furthermore, test chips can be adapted to detect other
      pathogens for a differential diagnosis in the field. The flexibility,
      reliability, and robustness of this technology hold much promise for its use as a
      novel molecular diagnostic platform in developing countries.

PMID- 24885207
TI  - Genome analysis and CRISPR typing of Salmonella enterica serovar Virchow.
AB  - BACKGROUND: Salmonella enterica subsp. enterica serovar Virchow has been
      recognized as a significant health burden in Asia, Australia and Europe. In
      addition to its global distribution, S. Virchow is clinically significant due to
      the frequency at which it causes invasive infections and its association with
      outbreaks arising from food-borne transmission. Here, we examine the genome of an
      invasive isolate of S. Virchow SVQ1 (phage type 8) from an outbreak in southeast
      Queensland, Australia. In addition to identifying new potential genotyping
      targets that could be used for discriminating between S. Virchow strains in
      outbreak scenarios, we also aimed to carry out a comprehensive comparative
      analysis of the S. Virchow genomes. RESULTS: Genome comparisons between S.
      Virchow SVQ1 and S. Virchow SL491, a previously published strain, identified a
      high degree of genomic similarity between the two strains with fewer than 200
      single nucleotide differences. Clustered Regularly Interspaced Palindromic
      Repeats (CRISPR) regions were identified as a highly variable region that could
      be used to discriminate between S. Virchow isolates. We amplified and sequenced
      the CRISPR regions of fifteen S. Virchow isolates collected from seven different
      outbreaks across Australia. We observed three allelic types of the CRISPR region
      from these isolates based on the presence/absence of the spacers and were able to
      discriminate S. Virchow phage type 8 isolates originating from different
      outbreaks. A comparison with 27 published Salmonella genomes found that the S.
      Virchow SVQ1 genome encodes 11 previously described Salmonella Pathogenicity
      Islands (SPI), as well as additional genomic islands including a remnant
      integrative conjugative element that is distinct from SPI-7. In addition, the S.
      Virchow genome possesses a novel prophage that encodes the Type III secretion
      system effector protein SopE, a key Salmonella virulence factor. The prophage
      shares very little similarity to the SopE prophages found in other Salmonella
      serovars suggesting an independent acquisition of sopE. CONCLUSIONS: The
      availability of this genome will serve as a genome template and facilitate
      further studies on understanding the virulence and global distribution of the S.
      Virchow serovar, as well as the development of genotyping methods for outbreak
      investigations.

PMID- 24885208
TI  - The Carpathian range represents a weak genetic barrier in South-East Europe.
AB  - BACKGROUND: In the present study we have assessed whether the Carpathian
      Mountains represent a genetic barrier in East Europe. Therefore, we have analyzed
      the mtDNA of 128 native individuals of Romania: 62 of them from the North of
      Romania, and 66 from South Romania. RESULTS: We have analyzed their mtDNA
      variability in the context of other European and Near Eastern populations through
      multivariate analyses. The results show that regarding the mtDNA haplogroup and
      haplotype distributions the Romanian groups living outside the Carpathian range
      (South Romania) displayed some degree of genetic differentiation compared to
      those living within the Carpahian range (North Romania). CONCLUSION: The main
      differentiation between the mtDNA variability of the groups from North and South
      Romania can be attributed to the demographic movements from East to West
      (prehistoric or historic) that differently affected in these regions, suggesting
      that the Carpathian mountain range represents a weak genetic barrier in South
      East Europe.

PMID- 24885209
TI  - Distribution of superantigens in group A streptococcal isolates from Salvador,
      Brazil.
AB  - BACKGROUND: Group A streptococcus (GAS) causes invasive disease, superficial
      disease, and can asymptomatically colonize humans. Superantigens are one
      virulence factor found in GAS. Previous studies found associations between the
      genes that encode superantigens and emm type of GAS. It is unknown if these
      associations are due to underlying biological factors that limit the distribution
      of superantigens or, alternatively, if these associations are due to the
      expansion of local GAS linages where these studies took place. To further address
      this question we screened GAS isolates collected from Salvador, Brazil for 11
      known superantigen genes. METHODS: Seventy-seven GAS isolates were screened by
      PCR for superantigen genes. These superantigen genes were speA, speC, speG, speH,
      speI, speJ, speK, speL, speM, ssa, and smeZ. We used Fisher's two-sided exact
      test to identify associations between superantigens and GAS emm type. We then
      compared our results to previous reports of superantigen prevalence and
      superantigen association with emm type. RESULTS: In our collection we found
      several emm type and superantigen genotype combinations that have previously been
      reported in isolates from Europe and Australia. We also found that speA was
      significantly associated with emm type 1, and that speC was significantly
      associated with emm type 12. CONCLUSIONS: Our study reports superantigen
      genotypes of GAS from a region of the world that is lacking this information. We
      found evidence of common GAS superantigen genotypes that are spread worldwide as
      well as novel superantigen genotypes that, so far, are unique to Brazil.

PMID- 24885210
TI  - The usefulness of "corrected" body mass index vs. self-reported body mass index:
      comparing the population distributions, sensitivity, specificity, and predictive
      utility of three correction equations using Canadian population-based data.
AB  - BACKGROUND: National data on body mass index (BMI), computed from self-reported
      height and weight, is readily available for many populations including the
      Canadian population. Because self-reported weight is found to be systematically
      under-reported, it has been proposed that the bias in self-reported BMI can be
      corrected using equations derived from data sets which include both self-reported
      and measured height and weight. Such correction equations have been developed and
      adopted. We aim to evaluate the usefulness (i.e., distributional similarity;
      sensitivity and specificity; and predictive utility vis-a-vis disease outcomes)
      of existing and new correction equations in population-based research. METHODS:
      The Canadian Community Health Surveys from 2005 and 2008 include both measured
      and self-reported values of height and weight, which allows for construction and
      evaluation of correction equations. We focused on adults age 18-65, and compared
      three correction equations (two correcting weight only, and one correcting BMI)
      against self-reported and measured BMI. We first compared population
      distributions of BMI. Second, we compared the sensitivity and specificity of self
      reported BMI and corrected BMI against measured BMI. Third, we compared the self
      reported and corrected BMI in terms of association with health outcomes using
      logistic regression. RESULTS: All corrections outperformed self-report when
      estimating the full BMI distribution; the weight-only correction outperformed the
      BMI-only correction for females in the 23-28 kg/m2 BMI range. In terms of
      sensitivity/specificity, when estimating obesity prevalence, corrected values of
      BMI (from any equation) were superior to self-report. In terms of modelling BMI
      disease outcome associations, findings were mixed, with no correction proving
      consistently superior to self-report. CONCLUSIONS: If researchers are interested
      in modelling the full population distribution of BMI, or estimating the
      prevalence of obesity in a population, then a correction of any kind included in
      this study is recommended. If the researcher is interested in using BMI as a
      predictor variable for modelling disease, then both self-reported and corrected
      BMI result in biased estimates of association.

PMID- 24885211
TI  - Collaboration between municipal and specialist public health care in tuberculosis
      screening in Norway.
AB  - BACKGROUND: About 90% of new tuberculosis (TB) cases in Norway appear among
      immigrants from high incidence countries. There is a compulsory governmental
      tuberculosis screening programme for immigrants; immigrants with positive
      screening results are to be referred from municipal health care to the specialist
      health care for follow-up. Recent studies of the screening programme have shown
      inadequate follow-up. One of the main problems has been that patients referred
      for follow-up have not attended their appointment at the specialist health
      care.TB screening in the municipality of Trondheim is done by two different
      teams: the Refugee Healthcare Centre (RHC) screens refugees and the Vaccination
      and Infection Control Office (VICO) screens all the other groups. Patients with
      positive findings on screening are referred to the hospital's Pulmonary Out
      patient Department (POPD). The municipal and referral level public health care
      initiated a project aiming to improve follow-up through closer collaboration.
      METHODS: An intervention group and a pre-intervention control group were
      established for each screening group. During meetings between staff from the
      municipality and the POPD, inadequacies in the screening process were identified,
      and changes in procedures for summoning patients, and time and place for tests
      were implemented. For both the intervention group and the control group, time
      from referral until consultation at the POPD and number of patients that attended
      their first appointment were registered and compared. RESULTS: In the VICO group,
      97/134 (72%) of the controls and 109/123 (89%) of the intervention group attended
      their first appointment at the POPD after 30 weeks (median) and 10 weeks,
      respectively. In the RHC group 28/46 (61%) of the controls and 55/59 (93%) in the
      intervention group attended their first appointment after 15 and 8 weeks (median)
      respectively. CONCLUSION: Increased collaboration between the municipal and
      specialist health care can improve the follow-up of positive TB screening
      results.

PMID- 24885212
TI  - Functions of behavior change interventions when implementing multi-professional
      teamwork at an emergency department: a comparative case study.
AB  - BACKGROUND: While there is strong support for the benefits of working in multi
      professional teams in health care, the implementation of multi-professional
      teamwork is reported to be complex and challenging. Implementation strategies
      combining multiple behavior change interventions are recommended, but the
      understanding of how and why the behavior change interventions influence staff
      behavior is limited. There is a lack of studies focusing on the functions of
      different behavior change interventions and the mechanisms driving behavior
      change. In this study, applied behavior analysis is used to analyze the function
      and impact of different behavior change interventions when implementing multi
      professional teamwork. METHODS: A comparative case study design was applied. Two
      sections of an emergency department implemented multi-professional teamwork
      involving changes in work processes, aimed at increasing inter-professional
      collaboration. Behavior change interventions and staff behavior change were
      studied using observations, interviews and document analysis. Using a hybrid
      thematic analysis, the behavior change interventions were categorized according
      to the DCOM(r) model. The functions of the behavior change interventions were
      then analyzed using applied behavior analysis. RESULTS: The two sections used
      different behavior change interventions, resulting in a large difference in the
      degree of staff behavior change. The successful section enabled staff performance
      of teamwork behaviors with a strategy based on ongoing problem-solving and
      frequent clarification of directions. Managerial feedback initially played an
      important role in motivating teamwork behaviors. Gradually, as staff started to
      experience positive outcomes of the intervention, motivation for teamwork
      behaviors was replaced by positive task-generated feedback. CONCLUSIONS: The
      functional perspective of applied behavior analysis offers insight into the
      behavioral mechanisms that describe how and why behavior change interventions
      influence staff behavior. The analysis demonstrates how enabling behavior change
      interventions, managerial feedback and task-related feedback interact in their
      influence on behavior and have complementary functions during different stages of
      implementation.

PMID- 24885213
TI  - Social capital in association with health status of women in reproductive age:
      study protocol for a sequential explanatory mixed methods study.
AB  - BACKGROUND: Women's health is a general health priority. Preserving and improving
      women's health is not only a basic human right, but it is also essential for the
      health of all nations. Women's health in Reproductive age affects long-term
      health of theirs, their family members, and community. Origins of health
      inequalities are very complicated. Health outcomes are influenced by biological,
      social and political factors, so to improve women's health it is necessary to
      recognize all these factors. Social capital is one of the social determinants of
      health that might play a considerable role in health inequalities. The
      association between social capital and health varies according on the sample
      studied, the type of health outcome and the context in which it is studied. This
      mixed methods study was designed to determine and explore of relationship between
      social capital and health status of women of reproductive age in Tehran (capital
      city of Iran) with its specific social-cultural characteristics. METHODS/DESIGN:
      This study is sequential explanatory mixed methods study, follow-up explanations
      variant, with two strands (phases). This design will be implemented in two
      distinct phases. The first phase is a population-based cross-sectional survey on
      770 women of reproductive age residing in any of the 22 municipal districts
      across Tehran. Based on a need to further understand the quantitative results,
      researchers will implement a second qualitative phase that is designed to help
      explain the initial quantitative results. Finally, the researchers will present
      an interpretation about explanation of quantitative results using the qualitative
      data. DISCUSSION: This study promotes women's health by determining the
      priorities and designing evidence-based interventions founded on the basic and
      insightful information provided on social capital and the status of the health of
      women.

PMID- 24885214
TI  - Who could benefit the most from using a computer-aided detection system in full
      field digital mammography?
AB  - BACKGROUND: The computer-aided detection (CAD) system on mammography has the
      potential to assist radiologists in breast cancer screening. The purpose of this
      study is to evaluate the diagnostic performance of the CAD system in full-field
      digital mammography for detecting breast cancer when used by dedicated breast
      radiologist (BR) and radiology resident (RR), and to reveal who could benefit the
      most from a CAD application. METHODS: We retrospectively chose 100 image sets
      from mammographies performed with CAD between June 2008 and June 2010. Thirty
      masses (15 benign and 15 malignant), 30 microcalcifications (15 benign and 15
      malignant), and 40 normal mammography images were included. The participating
      radiologists consisted of 7 BRs and 13 RRs. We calculated the sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      for total, normal plus microcalcification and normal plus mass both with and
      without CAD use for each reader. We compared the diagnostic performance values
      obtained with and without CAD use for the BR and RR groups, respectively. The
      reading time reviewing one set of 100 images and time reduction with CAD use for
      the BR and RR groups were also evaluated. RESULTS: The diagnostic performance was
      generally higher in the BR group than in the RR group. Sensitivity improved with
      CAD use in the BR and RR groups (from 81.10 to 84.29% for BR; 75.38 to 77.95% for
      RR). A tendency for improvement in all diagnostic performance values was observed
      in the BR group, whereas in the RR group, sensitivity improved but specificity,
      PPV, and NPV did not. None of the diagnostic performance parameters were
      significantly different. The mean reading time was shortened with CAD use in both
      the BR and RR groups (111.6 minutes to 94.3 minutes for BR; 135.5 minutes to
      109.8 minutes for RR). The mean time reduction was higher for the RR than that in
      the BR group. CONCLUSIONS: CAD was helpful for dedicated BRs to improve their
      diagnostic performance and for RRs to improve the sensitivity in a screening
      setting. CAD could be essential for radiologists by decreasing reading time
      without decreasing diagnostic performance.

PMID- 24885215
TI  - Transcriptome profiling confirmed correlations between symptoms and
      transcriptional changes in RDV infected rice and revealed nucleolus as a possible
      target of RDV manipulation.
AB  - BACKGROUND: Rice dwarf virus (RDV) is the causal agent of rice dwarf disease,
      which limits rice production in many areas of south East Asia. Transcriptional
      changes of rice in response to RDV infection have been characterized by Shimizu
      et al. and Satoh et al.. Both studies found induction of defense related genes
      and correlations between transcriptional changes and symptom development in RDV
      infected rice. However, the same rice cultivar, namely Nipponbare belonging to
      the Japonic subspecies of rice was used in both studies. METHODS: Gene expression
      changes of the indica subspecies of rice, namely Oryza sativa L. ssp. indica cv
      Yixiang2292 that show moderate resistance to RDV, in response to RDV infection
      were characterized using an Affymetrix Rice Genome Array. Differentially
      expressed genes (DEGs) were classified according to their Gene Ontology (GO)
      annotation. The effects of transient expression of Pns11 in Nicotiana
      benthaminana on the expression of nucleolar genes were studied using real-time
      PCR (RT-PCR). RESULTS: 856 genes involved in defense or other physiological
      processes were identified to be DEGs, most of which showed up-regulation.
      Ribosome- and nucleolus related genes were significantly enriched in the DEGs.
      Representative genes related to nucleolar function exhibited altered expression
      in N. benthaminana plants transiently expressing Pns11 of RDV. CONCLUSIONS:
      Induction of defense related genes is common for rice infected with RDV. There is
      a co-relation between symptom severity and transcriptional alteration in RDV
      infected rice. Besides ribosome, RDV may also target nucleolus to manipulate the
      translation machinery of rice. Given the tight links between nucleolus and
      ribosome, it is intriguing to speculate that RDV may enhance expression of
      ribosomal genes by targeting nucleolus through Pns11.

PMID- 24885216
TI  - Changes in the activity of adult stages of Dermacentor reticulatus (Ixodida:
      Amblyommidae) induced by weather factors in eastern Poland.
AB  - BACKGROUND: The host-seeking activity in Dermacentor reticulatus ticks undergoes
      rhythmical changes correlated with environmental conditions. Therefore, this
      study is focused on investigating the activity of adult stages of the species
      during weather changes occurring in winter months in eastern Poland, i.e. a
      period of tick diapause. METHODS: D. reticulatus ticks were collected in a meadow
      ecosystem near Lublin (eastern Poland, 51 degrees 36'N, 22 degrees 58'E) between
      the third decade of November 2011 and the third decade of January 2012. During
      each collection, temperature and humidity were measured at the soil surface and
      at a height of 25 cm and the differences (delta) in the parameters between the
      two measurement points were calculated. RESULTS: During one hour of our
      observation, from 0 to 42 specimens were collected, with the greatest numbers (25
      40 specimens) between late November and mid- December. The activity of adult D.
      reticulatus (females and males in total) depended on soil and air temperature (r
      = -0.6986, p < 0.05). Soil and air humidity did not exert an impact on the
      questing behaviour of adult stages. In turn, the greater the moisture delta
      between these two measurement points was, the greater the activity of the adult
      tick stages was observed.Our investigations have demonstrated differences in the
      questing behaviour between D. reticulatus females and males correlated with
      environmental conditions. The temperatures of soil and air increased the
      migratory activity in females but did not affect migration of male ticks. In
      turn, the deltas of temperatures (r = -0.6986, p < 0.05) and humidity (r =
      0.6829, p < 0.05) did not have a statistically significant effect on stimulation
      of female activity but they induced significant changes on the behaviour of
      males, for which we found a highly negative correlation between the number of
      active specimens and the temperature delta (r = -0.7276, p < 0.05) and a highly
      positive correlation with the humidity delta (r = 0.8199, p < 0.01). CONCLUSIONS:
      Weather changes can be accompanied by activity of adult D. reticulatus even in
      their winter diapause period. Therefore, there is an increased threat to human
      and animal health posed by tick-borne diseases.

PMID- 24885217
TI  - Influence of antiTNF-alpha antibody treatment on fracture healing under chronic
      inflammation.
AB  - BACKGROUND: The overexpression of tumor necrosis factor (TNF)-alpha leads to
      systemic as well as local loss of bone and cartilage and is also an important
      regulator during fracture healing. In this study, we investigate how TNF-alpha
      inhibition using a targeted monoclonal antibody affects fracture healing in a TNF
      alpha driven animal model of human rheumatoid arthritis (RA) and elucidate the
      question whether enduring the anti TNF-alpha therapy after trauma is beneficial
      or not. METHODS: A standardized femur fracture was applied to wild type and human
      TNF-alpha transgenic mice (hTNFtg mice), which develop an RA-like chronic
      polyarthritis. hTNFtg animals were treated with anti-TNF antibody (Infliximab)
      during the fracture repair. Untreated animals served as controls. Fracture
      healing was evaluated after 14 and 28 days of treatment by clinical assessment,
      biomechanical testing and histomorphometry. RESULTS: High levels of TNF-alpha
      influence fracture healing negatively, lead to reduced cartilage and more soft
      tissue in the callus as well as decreased biomechanical bone stability. Blocking
      TNF-alpha in hTNFtg mice lead to similar biomechanical and histomorphometrical
      properties as in wild type. CONCLUSIONS: High levels of TNF-alpha during chronic
      inflammation have a negative impact on fracture healing. Our data suggest that
      TNF-alpha inhibition by an anti-TNF antibody does not interfere with fracture
      healing.

PMID- 24885218
TI  - Patterns of non-compliant buprenorphine, levomethadone, and methadone use among
      opioid dependent persons in treatment.
AB  - BACKGROUND: The non-compliant use of opioid substitution treatment (OST)
      medicines is widespread and well-documented. However, less is known about
      characteristics of non-compliant OST medicine use and the factors that predict
      it. The two main goals of this study are to compare characteristics of non
      compliant levomethadone, methadone, and buprenorphine use and to explore factors
      that may differentially predict it among opioid dependent persons in treatment.
      METHODS: Data from 595 opioid dependent patients with non-compliant OST medicine
      use were analyzed. Characteristics of use between substances were compared using
      chi-squared tests and predictive factors were explored through multinomial
      logistic regressions. RESULTS: Non-compliant levomethadone and methadone use was
      characterized by more frequent parallel consumption of other psychoactive
      substances and intravenous use, whereas buprenorphine was more often procured
      without a prescription. Regarding predictive factors, methadone was perceived to
      relieve withdrawal symptoms better than buprenorphine and levomethadone was
      perceived as being better at modulating the effects of other substances and worst
      at enhancing mood. CONCLUSIONS: Patterns of non-compliant use differ according to
      OST medicine. These patterns are considered with the reduction of non-compliant
      use and the improvement of treatment in mind.

PMID- 24885219
TI  - Successful surgical management of pace-marker induced infective endocarditis
      under the guidance of real-time three-dimensional trans-esophageal
      echocardiogram.
AB  - The infection of cardiac implantable electronic device is a serious and
      potentially lethal complication. Accurate preoperative evaluation of location of
      vegetation, cardiac valve pathology is of paramount important. We reported a case
      of 71-year-old male patient who suffered from pacemaker endocarditis was given
      suitable surgical treatment under the guidance of real-time three-dimensional
      trans-esophageal echocardiogram.

PMID- 24885220
TI  - Impact of emergency department probiotic treatment of pediatric gastroenteritis:
      study protocol for the PROGUT (Probiotic Regimen for Outpatient Gastroenteritis
      Utility of Treatment) randomized controlled trial.
AB  - BACKGROUND: The burden of acute gastroenteritis on children and their families
      continues to be enormous. Probiotics, defined as viable microbial preparations
      that have a beneficial effect on the health of the host, represent a rapidly
      expanding field. Although clinical trials in children with gastroenteritis have
      been performed, most have significant flaws, and guidelines do not consistently
      endorse their use. METHODS/DESIGN: PROGUT is a randomized, placebo-controlled,
      double-blind, five-center, Canadian, emergency department trial. Children aged 3
      months to 48 months who present between November 2013 and June 2017 with <72
      hours of gastroenteritis symptoms will be assessed for eligibility. A total of
      886 children will be randomized (1:1 allocation via an internet based, third
      party, randomization service) to receive 5 days of a combination probiotic agent
      (Lactobacillus rhamnosus and L. helveticus) or placebo. All participants,
      caregivers, and outcome assessors will be blinded to group assignment. The study
      includes three key outcomes: 1) clinical - the development of moderate to severe
      disease following an emergency department (ED) evaluation that employs a
      validated clinical score (Modified Vesikari Scale); 2) safety - side effect; and
      3) mechanism - fecal secretory immunoglobulin A levels. DISCUSSION: Definitive
      data are lacking to guide the clinical use of probiotics in children with acute
      gastroenteritis. Hence, probiotics are rarely prescribed by North American
      physicians. However, the following current trends obligate an urgent assessment:
      1) probiotics are sold as food supplements, and manufacturers can encourage their
      use while their relevance has yet to be established; 2) North American and
      European government agencies remain concerned about their value and safety; 3)
      some institutions are now recommending the routine use of probiotics; and 4)
      parents of affected children are often providing probiotics. With probiotic
      consumption increasing in the absence of solid evidence, there is a need to
      conduct this definitive trial to overcome the limitations of prior work in this
      field. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01853124; first registered 9
      May 2013.

PMID- 24885221
TI  - Hemoglobins in the genome of the cryptomonad Guillardia theta.
AB  - Cryptomonads, are a lineage of unicellular and mostly photosynthetic algae, that
      acquired their plastids through the "secondary" endosymbiosis of a red alga - and
      still retain the nuclear genome (nucleomorph) of the latter. We find that the
      genome of the cryptomonad Guillardia theta comprises genes coding for 13 globin
      domains, of which 6 occur within two large chimeric proteins. All the sequences
      adhere to the vertebrate 3/3 myoglobin fold. Although several globins have no
      introns, the remainder have atypical intron locations. Bayesian phylogenetic
      analyses suggest that the G. theta Hbs are related to the stramenopile and
      chlorophyte single domain globins.

PMID- 24885222
TI  - SPECT/CT lymphoscintigraphy of sentinel node(s) for superselective prophylactic
      irradiation of the neck in cN0 head and neck cancer patients: a prospective phase
      I feasibility study.
AB  - BACKGROUND: Clinically node negative HNSCC patients have a risk ranging between
      18 and 45% of occult metastases, making prophylactic irradiation mandatory.
      Selective irradiation of nodal target volume based on international guidelines is
      practice. Anyway, about half the tumours lying in an anatomical subsite known to
      potentially drain bilaterally effectively do so, leading to unnecessary large
      volume irradiation. Moreover, 15% of the tumours show drainage outside of
      predicted basin, increasing the risk for potential geographical misses. Three
      dimensional SPECT/CT lymphoscintigraphy (LS) of sentinel node(s) may help to
      individualize nodal target volume selection. This prospective phase I study
      explores its feasibility and the dosimetric impact. METHODS: Ten cN0 HNSCC
      patients eligible for definitive radiotherapy were imaged with SPECT/CT after
      99mTc nanocolloid injection around the tumour. The neck levels containing up to
      four hottest nodes were identified and selected for prophylactic irradiation
      (CTVn-LS) by volumetric modulated arc therapy. A comparative virtual planning was
      performed with volumes selected according to international guidelines (CTVn-IG).
      RESULTS: Migration was observed in all patients (one with gamma probe only). 2.9
      sentinel nodes were detected per patient on average. In some patients, accurate
      localization was difficult when not using thermoplastic mask for SPECT/CT. CTVn
      LS was totally encompassed by CTVn-IG in all patients but one (unpredicted
      drainage in retropharyngeal level). On average, CTVn-LS and related planning
      target volumes were two times smaller than IG ones. This led to significant dose
      decrease in identified organs at risk as well as remaining volume at risk.
      CONCLUSIONS: SPECT/CT LS is a promising tool to individualize prophylactic node
      CTV in cN0 HNSCC patients eligible for definitive radiotherapy. Oncological
      safety must be confirmed by ongoing phase II study.

PMID- 24885224
TI  - Senior physiotherapy students as standardised patients for junior students
      enhances self-efficacy and satisfaction in both junior and senior students.
AB  - BACKGROUND: Standardised patients are used in medical education to expose
      students to clinical contexts and facilitate transition to clinical practice, and
      this approach is gaining momentum in physiotherapy programs. Expense and
      availability of trained standardised patients are factors limiting widespread
      adoption, and accessing clinical visits with real patients can be challenging.
      This study addressed these issues by engaging senior students as standardised
      patients for junior students. It evaluated how this approach impacted self
      reported constructs of both the junior and senior students. METHODS: Learning
      activities for undergraduate physiotherapy students were developed in five
      courses (Neurology, Cardiorespiratory and three Musculoskeletal courses) so that
      junior students (Year 2 and 3) could develop skills and confidence in patient
      interview, physical examination and patient management through their interaction
      with standardised patients played by senior students (Year 4). Surveys were
      administered before and after the interactions to record junior students' self
      reported confidence, communication, preparedness for clinic, and insight into
      their abilities; and senior students' confidence and insight into what it is like
      to be a patient. Satisfaction regarding this learning approach was surveyed in
      both the junior and senior students. RESULTS: A total of 253 students completed
      the surveys (mean 92.5% response rate). Across all courses, junior students
      reported a significant (all P < 0.037) improvement following the standardised
      patient interaction in their: preparedness for clinic, communication with
      clients, confidence with practical skills, and understanding of their strengths
      and weaknesses in relation to the learning activities. Senior students
      demonstrated a significant improvement in their confidence in providing feedback
      and insight into their own learning (P < 0.001). All students reported high
      satisfaction with this learning experience (mean score 8.5/10). CONCLUSION: This
      new approach to peer-assisted learning using senior students as standardised
      patients resulted in positive experiences for both junior and senior students
      across a variety of physiotherapy areas, activities, and stages within a
      physiotherapy program. These findings support the engagement of senior students
      as standardised patients to enhance learning within physiotherapy programs, and
      may have application across other disciplines to address challenges associated
      with accessing real patients via clinical visits or utilising actors as
      standardised patients.

PMID- 24885223
TI  - Six1 is a key regulator of the developmental and evolutionary architecture of
      sensory neurons in craniates.
AB  - BACKGROUND: Various senses and sensory nerve architectures of animals have
      evolved during adaptation to exploit diverse environments. In craniates, the
      trunk sensory system has evolved from simple mechanosensory neurons inside the
      spinal cord (intramedullary), called Rohon-Beard (RB) cells, to multimodal
      sensory neurons of dorsal root ganglia (DRG) outside the spinal cord
      (extramedullary). The fish and amphibian trunk sensory systems switch from RB
      cells to DRG during development, while amniotes rely exclusively on the DRG
      system. The mechanisms underlying the ontogenic switching and its link to
      phylogenetic transition remain unknown. RESULTS: In Xenopus, Six1 overexpression
      promoted precocious apoptosis of RB cells and emergence of extramedullary sensory
      neurons, whereas Six1 knockdown delayed the reduction in RB cell number. Genetic
      ablation of Six1 and Six4 in mice led to the appearance of intramedullary sensory
      neuron-like cells as a result of medial migration of neural crest cells into the
      spinal cord and production of immature DRG neurons and fused DRG. Restoration of
      SIX1 expression in the neural crest-linage partially rescued the phenotype,
      indicating the cell autonomous requirements of SIX1 for normal extramedullary
      sensory neurogenesis. Mouse Six1 enhancer that mediates the expression in DRG
      neurons activated transcription in Xenopus RB cells earlier than endogenous six1
      expression, suggesting earlier onset of mouse SIX1 expression than Xenopus during
      sensory development. CONCLUSIONS: The results indicated the critical role of Six1
      in transition of RB cells to DRG neurons during Xenopus development and
      establishment of exclusive DRG system of mice. The study provided evidence that
      early appearance of SIX1 expression, which correlated with mouse Six1 enhancer,
      is essential for the formation of DRG-dominant system in mice, suggesting that
      heterochronic changes in Six1 enhancer sequence play an important role in
      alteration of trunk sensory architecture and contribute to the evolution of the
      trunk sensory system.

PMID- 24885225
TI  - RpoS integrates CRP, Fis, and PhoP signaling pathways to control Salmonella Typhi
      hlyE expression.
AB  - BACKGROUND: SPI-18 is a pathogenicity island found in some Salmonella enterica
      serovars, including S. Typhi. SPI-18 harbors two ORFs organized into an operon,
      hlyE and taiA genes, both implicated in virulence. Regarding the hlyE regulation
      in S. Typhi, it has been reported that RpoS participates as transcriptional up
      regulator under low pH and high osmolarity. In addition, CRP down-regulates hlyE
      expression during exponential growth. Previously, it has been suggested that
      there is another factor related to catabolite repression, different from CRP,
      involved in the down-regulation of hlyE. Moreover, PhoP-dependent hlyE up
      regulation has been reported in bacteria cultured simultaneously under low pH and
      low concentration of Mg2+. Nevertheless, the relative contribution of each
      environmental signal is not completely clear. In this work we aimed to better
      understand the regulation of hlyE in S. Typhi and the integration of different
      environmental signals through global regulators. RESULTS: We found that Fis
      participates as a CRP-independent glucose-dependent down-regulator of hlyE. Also,
      Fis and CRP seem to exert the repression over hlyE through down-regulating rpoS.
      Moreover, PhoP up-regulates hlyE expression via rpoS under low pH and low Mg2+
      conditions. CONCLUSIONS: All these results together show that, at least under the
      tested conditions, RpoS is the central regulator in the hlyE regulatory network,
      integrating multiple environmental signals and global regulators.

PMID- 24885226
TI  - Children's perception on obesity and quality of life: a Mexican survey.
AB  - BACKGROUND: Child obesity has become a major health problem worldwide. In order
      to design successful intervention strategies, it is necessary to understand how
      children perceive obesity and its consequences. METHODS: With the aim to evaluate
      scholar children perception of obesity as a significant factor on the quality of
      life, we developed and validated the "Obesity impact on the quality of life
      perception-questionnaire" (ObI-Q). We surveyed 1335 healthy children aged 6-12
      years, randomly selected from elementary schools in Mexico City. The ObI-Q
      comprises eight multiple-choice items that explore aspects related to the quality
      of life during adult life; such as health, life span, emotional status,
      lifestyle, social recognition and economic status. In order to identify
      perceptional modifier factors, results were analyzed through multivariable
      logistic regression. Variables included gender, age, and child nutritional
      status, as well as the child's perception of parental nutritional status.
      RESULTS: ObI-Q results showed that most children (64.71%) considered obesity as a
      negative condition that influences health and social performance. This perception
      was inversely related to age (OR = 0.64, p = 0.003), as well as to the perception
      of their mother nutritional status (OR = 0.47, p = 0.01). CONCLUSIONS: This study
      provides an overview of children's perception on obesity and its consequences.
      Because the high proportion of schoolchildren who do not view obesity as an
      adverse consequence to the quality of life, then the results of this study could
      be used as part of strategies for the prevention of overweight and obesity.

PMID- 24885227
TI  - Complex regional pain syndrome in a competitive athlete and regional osteoporosis
      assessed by dual-energy X-ray absorptiometry: a case report.
AB  - INTRODUCTION: Dual-energy X-ray absorptiometry is rarely utilized in the clinical
      care of patients with complex regional pain syndrome, but may be useful for the
      non-invasive determination of regional bone fragility and fracture risk, as well
      as muscular atrophy and regional body composition. This is the first report in
      the literature of complex regional pain syndrome and musculoskeletal co
      morbidities in an athlete, and is the first to focus on dual-energy X-ray
      absorptiometry for the clinical assessment of complex regional pain syndrome.
      CASE PRESENTATION: In this report, we describe the case of a 29-year-old
      Caucasian man with type 1 complex regional pain syndrome. His body mass index was
      29.4kg/m2 at the time of presentation. Despite severe complex regional pain
      syndrome in the left limb and long term use of a wheelchair, the patient
      participated in high-performance powerlifting. Dual-energy X-ray absorptiometry
      revealed marked unilateral differences in bone strength and lean mass between the
      affected regions and the contralateral regions. Low bone mineral density for age
      was found in the left hip, with Z-scores ranging from -2.2 to -3.0, and the
      patient had previously suffered two fractures. Bone density Z-scores in the right
      hip and legs were normal. CONCLUSIONS: Dual-energy X-ray absorptiometry is a
      valuable tool for the clinical investigation of musculoskeletal health in
      patients with complex regional pain syndrome. Regional osteoporosis in complex
      regional pain syndrome patients is complicated and should be investigated and
      monitored. Physical activity is possible for some complex regional pain syndrome
      patients, depending on the type of exercise and the region affected, and it may
      protect bone density and strength at non affected skeletal sites.

PMID- 24885228
TI  - Effects of astragalus injection on the TGFbeta/Smad pathway in the kidney in type
      2 diabetic mice.
AB  - BACKGROUND: In traditional Chinese medicine, astragalus injection is used to
      treat diabetic nephropathy (DN). The current study was conducted to determine the
      effects of astragalus injection on DN by assessing potential modulation of the
      transforming growth factor beta TGFbeta/Smad signaling pathway. METHODS:
      Diabetic, male KKAy mice, aged 14 weeks were randomly divided into a model group
      and an astragalus treatment group, while age-matched male C57BL/6J mice were
      selected as controls. The treatment group received daily intraperitoneal
      injections of astragalus (0.03 ml/10 g.d), while the model group received
      injections of an equivalent volume of saline. Mice were euthanized after 24
      weeks. Serum samples were obtained from animals in each group, and blood glucose,
      creatinine, and urea nitrogen levels were measured. Tissue samples from the
      kidney were used for morphometric studies. The expression of TGFbeta1, TGFbetaR
      Iota, Smad3, and Smad7 were evaluated using reverse transcription-polymerase
      chain reaction (RT-PCR), and western blot analysis. RESULTS: Mice in the model
      group became obese, and suffered complications, including hyperglycemia,
      polyuria, and proteinuria. Astragalus treatment significantly reduced
      albuminuria, improved renal function, and ameliorated changes in renal
      histopathology. Moreover, administration of astragalus injection increased Smad7
      expression, and inhibited the expression of TGFbetaR-Iota, Smad3 and its
      phosphorylation, and decreased the mRNA level of TGFbeta1. CONCLUSIONS: The
      TGFbeta/Smad signaling pathway plays an important role in the development of DN.
      Administration of astragalus injection could prevent or mitigate DN by
      rebalancing TGFbeta/Smad signaling, and could play a protective role in DN
      induced renal damage in KKAy mice.

PMID- 24885230
TI  - Differences in sickness absence between self-employed and employed doctors: a
      cross-sectional study on national sample of Norwegian doctors in 2010.
AB  - BACKGROUND: Doctors have a low prevalence of sickness absence. Employment status
      is a determinant in the multifactorial background of sickness absence. The effect
      of doctors' employment status on sickness absence is unexplored. The study
      compares the number of sickness absence days during the last 12 months and the
      impact of employment status, psychosocial work stress, self-rated health and
      demographics on sickness absence between self-employed practitioners and employed
      hospital doctors in Norway. METHODS: The study population consisted of a
      representative sample of 521 employed interns and consultants and 313 self
      employed GPs and private practice specialists in Norway, who received postal
      questionnaires in 2010. The questionnaires contained items on sickness absence
      days during the last 12 months, employment status, demographics, self-rated
      health, professional autonomy and psychosocial work stress. RESULTS: 84% (95% CI
      80 to 88%) of self-employed and 60% (95% CI 55 to 64%) of employed doctors
      reported no absence at all last year. In three multivariate logistic regression
      models with sickness absence as response variable, employment category was a
      highly significant predictor for absence vs. no absence, 1 to 3 days of absence
      vs. no absence and 4 to 99 days of absence vs. no absence), while in a model with
      100 or more days of absence vs. no absence, there was no difference between
      employment categories, suggesting that serious chronic disease or injury is less
      dependent on employment category. Average or poor self-rated health and low
      professional autonomy, were also significant predictors of sickness absence,
      while psychosocial work stress, age and gender were not. CONCLUSION: Self
      employed GPs and private practice specialist reported lower sickness absence than
      employed hospital doctors. Differences in sickness compensation, and
      organisational and individual factors may to a certain extent explain this
      finding.

PMID- 24885229
TI  - A comprehensive assessment of the transcriptome of cork oak (Quercus suber)
      through EST sequencing.
AB  - BACKGROUND: Cork oak (Quercus suber) is one of the rare trees with the ability to
      produce cork, a material widely used to make wine bottle stoppers, flooring and
      insulation materials, among many other uses. The molecular mechanisms of cork
      formation are still poorly understood, in great part due to the difficulty in
      studying a species with a long life-cycle and for which there is scarce
      molecular/genomic information. Cork oak forests are of great ecological
      importance and represent a major economic and social resource in Southern Europe
      and Northern Africa. However, global warming is threatening the cork oak forests
      by imposing thermal, hydric and many types of novel biotic stresses. Despite the
      economic and social value of the Q. suber species, few genomic resources have
      been developed, useful for biotechnological applications and improved forest
      management. RESULTS: We generated in excess of 7 million sequence reads, by
      pyrosequencing 21 normalized cDNA libraries derived from multiple Q. suber
      tissues and organs, developmental stages and physiological conditions. We
      deployed a stringent sequence processing and assembly pipeline that resulted in
      the identification of ~159,000 unigenes. These were annotated according to their
      similarity to known plant genes, to known Interpro domains, GO classes and E.C.
      numbers. The phylogenetic extent of this ESTs set was investigated, and we found
      that cork oak revealed a significant new gene space that is not covered by other
      model species or EST sequencing projects. The raw data, as well as the full
      annotated assembly, are now available to the community in a dedicated web portal
      at http://www.corkoakdb.org. CONCLUSIONS: This genomic resource represents the
      first trancriptome study in a cork producing species. It can be explored to
      develop new tools and approaches to understand stress responses and developmental
      processes in forest trees, as well as the molecular cascades underlying cork
      differentiation and disease response.

PMID- 24885231
TI  - Musculoskeletal conditions in children and adolescents managed in Australian
      primary care.
AB  - BACKGROUND: Primary care settings play a vital role in the early detection and
      appropriate management of musculoskeletal conditions in paediatric populations.
      However, little data exist regarding these conditions in a primary care context
      or on the presentation of specific musculoskeletal disorders in children. The aim
      of this study was to estimate the caseload and describe typical management of
      musculoskeletal conditions in children and adolescents presenting to primary care
      in Australia. METHODS: An analysis of data from the Bettering the Evaluation and
      Care of Health (BEACH) study was performed. The BEACH study is a continuous
      national study of general practice (GP) activity in Australia. We identified all
      GP encounters with children and adolescents over the past five years and
      extracted data on demographic details, the problems managed, and GP management of
      each problem. SAS statistical software was used to calculate robust proportions
      and after adjustment for the cluster, the 95% confidence intervals (CIs).
      RESULTS: From the period April 2006 to March 2011, there were 65,279 encounters
      with children and adolescents in the BEACH database. Of the 77,830 problems
      managed at these encounters, 4.9% (95%CI 4.7% to 5.1%) were musculoskeletal
      problems. The rate of musculoskeletal problems managed increased significantly
      with age, however there was a significant decrease for girls aged 15-17 years.
      Upper and lower limb conditions were the most common, followed by spine and trunk
      conditions. Spine and trunk conditions were significantly more likely to be
      managed with medication, but less likely to receive imaging, than upper or lower
      limb problems. CONCLUSIONS: Musculoskeletal problems in children and adolescents
      present a significant burden and an important challenge to the primary health
      care system in Australia. There is variability in rates of presentation between
      different age groups, gender and affected body region.

PMID- 24885232
TI  - A genomic copy number variant analysis implicates the MBD5 and HNRNPU genes in
      Chinese children with infantile spasms and expands the clinical spectrum of
      2q23.1 deletion.
AB  - BACKGROUND: Infantile spasms (IS) is a specific type of epileptic encephalopathy
      associated with severe developmental disabilities. Genetic factors are strongly
      implicated in IS, however, the exact genetic defects remain unknown in the
      majority of cases. Rare mutations in a single gene or in copy number variants
      (CNVs) have been implicated in IS of children in Western countries. The objective
      of this study was to dissect the role of copy number variations in Chinese
      children with infantile spasms. METHODS: We used the Agilent Human Genome CGH
      microarray 180 K for genome-wide detection of CNVs. Real-time qPCR was used to
      validate the CNVs. We performed genomic and medical annotations for individual
      CNVs to determine the pathogenicity of CNVs related to IS. RESULTS: We report
      herein the first genome-wide CNV analysis in children with IS, detecting a total
      of 14 CNVs in a cohort of 47 Chinese children with IS. Four CNVs (4/47 = 8.5%)
      (1q21.1 gain; 1q44, 2q31.1, and 17p13 loss) are considered to be pathogenic. The
      CNV loss at 17p13.3 contains PAFAH1B1 (LIS1), a causative gene for lissencephaly.
      Although the CNVs at 1q21.1, 1q44, and 2q23.1 have been previously implicated in
      a wide spectrum of clinical features including autism spectrum disorders (ASD)
      and generalized seizure, our study is the first report identifying them in
      individuals with a primary diagnosis of IS. The CNV loss in the 1q44 region
      contains HNRNPU, a strong candidate gene recently suggested in IS by the whole
      exome sequencing of children with IS. The CNV loss at 2q23.1 includes MBD5, a
      methyl-DNA binding protein that is a causative gene of ASD and a candidate gene
      for epileptic encephalopathy. We also report a distinct clinical presentation of
      IS, microcephaly, intellectual disability, and absent hallux in a case with the
      2q23.1 deletion. CONCLUSION: Our findings strongly support the role of CNVs in
      infantile spasms and expand the clinical spectrum associate with 2q23.1 deletion.
      In particular, our study implicates the HNRNPU and MBD5 genes in Chinese children
      with IS. Our study also supports that the molecular mechanisms of infantile
      spasms appear conserved among different ethnic backgrounds.

PMID- 24885233
TI  - Global spatiotemporal and genetic footprint of the H5N1 avian influenza virus.
AB  - BACKGROUND: Since 2005, the Qinghai-like lineage of the highly pathogenic avian
      influenza A virus H5N1 has rapidly spread westward to Europe, the Middle East and
      Africa, reaching a dominant level at a global scale in 2006. METHODS: Based on a
      combination of genetic sequence data and H5N1 outbreak information from 2005 to
      2011, we use an interdisciplinary approach to improve our understanding of the
      transmission pattern of this particular clade 2.2, and present cartography of
      global spatiotemporal transmission footprints with genetic characteristics.
      RESULTS: Four major viral transmission routes were derived with three sources-
      Russia, Mongolia, and the Middle East (Kuwait and Saudi Arabia)-in the three
      consecutive years 2005, 2006 and 2007. With spatiotemporal transmission along
      each route, genetic distances to isolate A/goose/Guangdong/1996 are becoming
      significantly larger, leading to a more challenging situation in certain regions
      like Korea, India, France, Germany, Nigeria and Sudan. Europe and India have had
      at least two incursions along multiple routes, causing a mixed virus situation.
      In addition, spatiotemporal distribution along the routes showed that 2007/2008
      was a temporal separation point for the infection of different host species;
      specifically, wild birds were the main host in 2005-2007/2008 and poultry was
      responsible for the genetic mutation in 2009-2011. "Global-to-local" and "high-to
      low latitude" transmission footprints have been observed. CONCLUSIONS: Our
      results suggest that both wild birds and poultry play important roles in the
      transmission of the H5N1 virus clade, but with different spatial, temporal, and
      genetic dominance. These characteristics necessitate that special attention be
      paid to countries along the transmission routes.

PMID- 24885234
TI  - The inhibitory effect of Mesembryanthemum edule (L.) bolus essential oil on some
      pathogenic fungal isolates.
AB  - BACKGROUND: Mesembryanthemum edule is a medicinal plant which has been indicated
      by Xhosa traditional healers in the treatment HIV associated diseases such as
      tuberculosis, dysentery, diabetic mellitus, laryngitis, mouth infections,
      ringworm eczema and vaginal infections. The investigation of the essential oil of
      this plant could help to verify the rationale behind the use of the plant as a
      cure for these illnesses. METHODS: The essential oil from M. edule was analysed
      by GC/MS. Concentration ranging from 0.005-5 mg/ml of the hydro-distilled
      essential oil was tested against some fungal strains, using micro-dilution
      method. The plant minimum inhibitory activity on the fungal strains was
      determined. RESULT: GC/MS analysis of the essential oil resulted in the
      identification of 28 compounds representing 99.99% of the total essential oil. A
      total amount of 10.6 and 36.61% constituents were obtained as monoterpenes and
      oxygenated monoterpenes. The amount of sesquiterpene hydrocarbons (3.58%) was low
      compared to the oxygenated sesquiterpenes with pick area of 9.28%. Total oil
      content of diterpenes and oxygenated diterpenes detected from the essential oil
      were 1.43% and 19.24%. The fatty acids and their methyl esters content present in
      the essential oil extract were found to be 19.25%. Antifungal activity of the
      essential oil extract tested against the pathogenic fungal, inhibited C. albican,
      C. krusei, C. rugosa, C. glabrata and C. neoformans with MICs range of 0.02-0.31
      mg/ml. the activity of the essential oil was found competing with nystatin and
      amphotericin B used as control. CONCLUSION: Having accounted the profile chemical
      constituent found in M. edule oil and its important antifungal properties, we
      consider that its essential oil might be useful in pharmaceutical and food
      industry as natural antibiotic and food preservative.

PMID- 24885235
TI  - Women participating in a web-based preconception study have a high prevalence of
      risk factors for adverse pregnancy outcomes.
AB  - BACKGROUND: Adverse pregnancy outcomes (APOs) can be increased by preconception
      risk factors and lifestyles.We measured the prevalence of preconception risk
      factors for APOs in a population of Italian women of childbearing age enrolled in
      a web-based study. METHODS: Participants were enrolled through a web platform
      (http://www.mammainforma.it). After enrollment, participants filled in a
      questionnaire regarding socio-demographic characteristics, clinical data and
      preconception risk factors for adverse pregnancy outcomes. Through logistic
      regression, we explored how the prevalence of risk factors was affected by age,
      education level, employment, parity, physician's recommendation and knowledge of
      the specific risk factor. RESULTS: We enrolled a total of 728 women. Sixty-two
      percent had a University degree, 84% were employed and 77% were planning their
      first pregnancy.Nearly 70% drank alcohol in any quantity; 16% were smokers; 6%
      was underweight; 21.4% was overweight; 51.6% did not assume folic acid; 22% was
      susceptible to rubella, 44.5% to hepatitis b and 13.2% to varicella.According to
      the multivariate analysis, compared to women who already had at least one
      pregnancy, nulliparous women had a higher BMI [OR 1.60 (CI 1.02;2.48)] and were
      less likely to be susceptible to rubella [OR 0.33 (CI 0.20;0.58)] and to be
      consuming alcohol [OR 0.47 (CI 0.31;0.70)] or cigarettes [OR 0.48 (CI
      0.26;0.90)].Appropriate knowledge was associated with a correct behavior
      regarding smoking, drinking alcohol and folic acid supplementation. CONCLUSIONS:
      This study shows that the prevalence of risk factors for APOs in our population
      is high.Interventions aimed at reducing risk factors for APOs are needed and, to
      this purpose, a web intervention may represent a feasible tool to integrate
      tailored information and to inform preconception counseling targeting a specific
      group of women planning a pregnancy who are engaged on the web.

PMID- 24885236
TI  - Translating a gene expression signature for multiple myeloma prognosis into a
      robust high-throughput assay for clinical use.
AB  - BACKGROUND: Widespread adoption of genomic technologies in the management of
      heterogeneous indications, including Multiple Myeloma, has been hindered by
      concern over variation between published gene expression signatures, difficulty
      in physician interpretation and the challenge of obtaining sufficient genetic
      material from limited patient specimens. METHODS: Since 2006, the 70-gene
      prognostic signature, developed by the University of Arkansas for Medical
      Sciences (UAMS) has been applied to over 4,700 patients in studies performed in 4
      countries and described in 17 peer-reviewed publications. Analysis of control
      sample and quality control data compiled over a 12-month period was performed.
      RESULTS: Over a 12 month period, the 70-gene prognosis score (range 0-100) of our
      multiple myeloma cell-line control sample had a standard deviation of 2.72 and a
      coefficient of variance of 0.03. The whole-genome microarray profile used to
      calculate a patient's GEP70 score can be generated with as little as 15 ng of
      total RNA; approximately 30,000 CD-138+ plasma cells. Results from each GEP70
      analysis are presented as either low (70-gene score <45.2) or high (>=45.2) risk
      for relapse (newly diagnosed setting) or shorter overall survival (relapse
      setting). A personalized and outcome-annotated gene expression heat map is
      provided to assist in the clinical interpretation of the result. CONCLUSIONS: The
      70-gene assay, commercialized under the name 'MyPRS(r)' (Myeloma Prognostic Risk
      Score) and performed in Signal Genetics' CLIA-certified high throughput flow
      cytometry and molecular profiling laboratory is a reproducible and standardized
      method of multiple myeloma prognostication.

PMID- 24885238
TI  - Spontaneous formation of one-dimensional hydrogen gas hydrate in carbon
      nanotubes.
AB  - We present molecular dynamics simulation evidence of spontaneous formation of
      quasi-one-dimensional (Q1D) hydrogen gas hydrates within single-walled carbon
      nanotubes (SW-CNTs) of nanometer-sized diameter (1-1.3 nm) near ambient
      temperature. Contrary to conventional 3D gas hydrates in which the guest
      molecules are typically contained in individual and isolated cages in the host
      lattice, the guest H2 molecules in the Q1D gas hydrates are contained within a 1D
      nanochannel in which the H2 molecules form a molecule wire. In particular, we
      show that in the (15,0) zigzag SW-CNT, the hexagonal H2 hydrate tends to form,
      with one H2 molecule per hexagonal prism, while in the (16,0) zigzag SW-CNT, the
      heptagonal H2 hydrate tends to form, with one H2 molecule per heptagonal prism.
      In contrast, in the (17,0) zigzag SW-CNT, the octagonal H2 hydrate can form, with
      either one H2 or two H2 molecules per pentagonal prism (single or double
      occupancy). Interestingly, in the hexagonal or heptagonal ice nanotube, the H2
      wire is solid-like as the axial diffusion constant is very low (<5 * 10(-10)
      cm(2)/s), whereas in the octagonal ice nanotube, the H2 wire is liquid-like as
      its axial diffusion constant is comparable to 10(-5) cm(2)/s. 

PMID- 24885237
TI  - Intermittent hypoxia-induced protein phosphatase 2A activation reduces PC12 cell
      proliferation and differentiation.
AB  - BACKGROUND: Intermittent hypoxia (IH) plays a critical role in sleep breathing
      disorder-associated hippocampus impairments, including neurocognitive deficits,
      irreversible memory and learning impairments. IH-induced neuronal injury in the
      hippocampus may result from reduced precursor cell proliferation and the relative
      numbers of postmitotic differentiated neurons. However, the mechanisms underlying
      IH-induced reactive oxygen species (ROS) generation effects on cell proliferation
      and neuronal differentiation remain largely unknown. RESULTS: ROS generation
      significantly increased after 1-4 days of IH without increased pheochromocytoma
      12 (PC12) cell death, which resulted in increased protein phosphatase 2A (PP2A)
      mRNA and protein levels. After 3-4 days of IH, extracellular signal-regulated
      kinases 1/2 (ERK1/2) protein phosphorylation decreased, which could be reversed
      by superoxide dismutase (SOD), 1,10-phenanthroline (Phe), the PP2A
      phosphorylation inhibitors, okadaic acid (OKA) and cantharidin, and the ERK
      phosphorylation activator nicotine (p < 0.05). In particular, the significantly
      reduced cell proliferation and increased proportions of cells in the G0/G1 phase
      after 1-4 days of IH (p < 0.05), which resulted in decreased numbers of PC12
      cells, could be reversed by treatment with SOD, Phe, PP2A inhibitors and an ERK
      activator. In addition, the numbers of nerve growth factor (NGF)-induced PC12
      cells with neurite outgrowths after 3-4 days of IH were less than those after 4
      days of RA, which was also reversed by SOD, Phe, PP2A inhibitors and an ERK
      activator. CONCLUSIONS: Our results suggest that IH-induced ROS generation
      increases PP2A activation and subsequently downregulates ERK1/2 activation, which
      results in inhibition of PC12 cell proliferation through G0/G1 phase arrest and
      NGF-induced neuronal differentiation.

PMID- 24885239
TI  - Individualized and institutionalized residential place-based discrimination and
      self-rated health: a cross-sectional study of the working-age general population
      in Osaka city, Japan.
AB  - BACKGROUND: Several studies have reported that individualized residential place
      based discrimination (PBD) affects residents' health. However, studies exploring
      the association between institutionalized PBD and health are scarce, especially
      in Asian countries including Japan. METHODS: A cross-sectional study was
      conducted with random two-stage sampling of 6191 adults aged 25-64 years in 100
      census tracts across Osaka city in 2011. Of 3244 respondents (response rate
      52.4%), 2963 were analyzed using multilevel logistic regression to examine the
      association of both individualized and institutionalized PBD with self-rated
      health (SRH) after adjustment for individual-level factors such as socioeconomic
      status (SES). An area-level PBD indicator was created by aggregating individual
      level PBD responses in each tract, representing a proxy for institutionalized
      PBD, i.e., the concept that living in a stigmatized neighborhood affects
      neighborhood health. 100 tracts were divided into quartiles in order. The health
      impact of area-level PBD was compared with that of area-level SES indicators
      (quartile) such as deprivation. RESULTS: After adjustment for individual-level
      PBD, the highest and third area-level PBD quartiles showed odds ratio (OR) 1.57
      (95% credible interval: 1.13-2.18) and 1.38 (0.99-1.92), respectively, for poor
      SRH compared with the lowest area-level PBD quartile. In a further SES-adjusted
      model, ORs of area-level PBD (highest and third quartile) were attenuated to 1.32
      and 1.31, respectively, but remained marginally significant, although those of
      the highest area-level not-home-owner (census-based indicator) and deprivation
      index quartiles were attenuated to 1.26 and 1.21, respectively, and not
      significant. Individual-level PBD showed significant OR 1.89 (1.33-2.81) for poor
      SRH in an age, sex, PBD and SES-adjusted model. CONCLUSION: Institutionalized PBD
      may be a more important environmental determinant of SRH than other area-level
      SES indicators such as deprivation. Although it may have a smaller health impact
      than individualized PBD, attention should be paid to invisible and unconscious
      aspects of institutionalized PBD to improve residents' health.

PMID- 24885240
TI  - Altered glutamyl-aminopeptidase activity and expression in renal neoplasms.
AB  - BACKGROUND: Advances in the knowledge of renal neoplasms have demonstrated the
      implication of several proteases in their genesis, growth and dissemination.
      Glutamyl-aminopeptidase (GAP) (EC. 3.4.11.7) is a zinc metallopeptidase with
      angiotensinase activity highly expressed in kidney tissues and its expression and
      activity have been associated wtih tumour development. METHODS: In this
      prospective study, GAP spectrofluorometric activity and immunohistochemical
      expression were analysed in clear-cell (CCRCC), papillary (PRCC) and chromophobe
      (ChRCC) renal cell carcinomas, and in renal oncocytoma (RO). Data obtained in
      tumour tissue were compared with those from the surrounding uninvolved kidney
      tissue. In CCRCC, classic pathological parameters such as grade, stage and tumour
      size were stratified following GAP data and analyzed for 5-year survival.
      RESULTS: GAP activity in both the membrane-bound and soluble fractions was
      sharply decreased and its immunohistochemical expression showed mild staining in
      the four histological types of renal tumours. Soluble and membrane-bound GAP
      activities correlated with tumour grade and size in CCRCCs. CONCLUSIONS: This
      study suggests a role for GAP in the neoplastic development of renal tumours and
      provides additional data for considering the activity and expression of this
      enzyme of interest in the diagnosis and prognosis of renal neoplasms.

PMID- 24885241
TI  - Serum activin A and B, and follistatin in critically ill patients with influenza
      A(H1N1) infection.
AB  - BACKGROUND: Activin A and its binding protein follistatin (FS) are increased in
      inflammatory disorders and sepsis. Overexpression of activin A in the lung causes
      similar histopathological changes as acute respiratory distress syndrome (ARDS).
      ARDS and severe respiratory failure are complications of influenza A(H1N1)
      infection. Interleukin 6 (IL-6), which in experimental studies increases after
      activin A release, is known to be related to the severity of H1N1 infection. Our
      aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and
      their association with the severity of respiratory failure in critically ill H1N1
      patients. METHODS: A substudy of a prospective, observational cohort of H1N1
      patients in Finnish intensive care units (ICU). Clinical information was recorded
      during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were
      measured at admission to ICU and on days 2 and 7. RESULTS: Blood samples from 29
      patients were analysed. At the time of admission to intensive care unit, elevated
      serum levels above the normal range for respective age group and sex were
      observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29
      patients, serial samples at all time points were available and in these the
      highest activin A, activin B and FS were above the normal range in 85%, 100% and
      46% of the patients, respectively. No difference in baseline or highest activin A
      or activin B was found in patients with or without acute lung injury (ALI) or
      ARDS (P > 0.05 for all). Peak levels of IL-6 were significantly elevated in
      ALI/ARDS patients. Peak activin A and activin A/FS were associated with
      ventilatory support free-days, severity of acute illness and length of ICU stay
      (P < 0.05 for all). CONCLUSIONS: Higher than normal values of these proteins were
      common in patients with H1N1 infection but we found no association with the
      severity of their respiratory failure.

PMID- 24885242
TI  - Design and implementation of a high yield production system for recombinant
      expression of peptides.
AB  - BACKGROUND: Making peptide pharmaceuticals involves challenging processes where
      many barriers, which include production and manufacture, need to be overcome. A
      non common but interesting research area is related to peptides with
      intracellular targets, which opens up new possibilities, allowing the modulation
      of processes occurring within the cell or interference with signaling pathways.
      However, if the bioactive sequence requires fusion to a carrier peptide to allow
      access into the cell, the resulting peptide could be such a length that
      traditional production could be difficult. The goal of the present study was the
      development of a flexible recombinant expression and purification system for
      peptides, as a contribution to the discovery and development of these potentially
      new drugs. RESULTS: In this work, a high throughput recombinant expression and
      purification system for production of cell penetrating peptides in Escherichia
      coli has been designed and implemented. The system designed produces target
      peptides in an insoluble form by fusion to a hexahistidine tagged ketosteroid
      isomerase which is then separated by a highly efficient thrombin cleavage
      reaction procedure. The expression system was tested on the anticancer peptides
      p53pAnt and PNC27. These peptides comprise the C-terminal region and the N
      terminal region of the protein p53, respectively, fused by its carboxyl terminal
      extreme to the cell penetrating peptide Penetratin. High yields of purified
      recombinant fused peptides were obtained in both cases; nevertheless, thrombin
      cleavage reaction was successful only for p53pAnt peptide release. The features
      of the system, together with the procedure developed, allow achievement of high
      production yields of over 30 mg of highly pure p53pAnt peptide per g of dry cell
      mass. It is proposed that the system could be used for production of other
      peptides at a similar yield. CONCLUSIONS: This study provides a system suitable
      for recombinant production of peptides for scientific research, including
      biological assays.

PMID- 24885243
TI  - Scandinavian systems monitoring the oral health in children and adolescents; an
      evaluation of their quality and utility in the light of modern perspectives of
      caries management.
AB  - BACKGROUND: Recording reliable oral health data is a challenge. The aims were a)
      to outline different Scandinavian systems of oral health monitoring, b) to
      evaluate the quality and utility of the collected data in the light of modern
      concepts of disease management and to suggest improvements. MATERIAL AND METHODS:
      The information for in this study was related to (a) children and adolescents,
      (b) oral health data and (c) routines for monitoring such data. This meant
      information available in the official web sites of the "KOSTRA-data"
      (Municipality-State-Report) in Norway, the Swedish National Board of Health and
      Welfare ("Socialstyrelsen") and Oral Health Register (the SCOR system, National
      Board of Health) in Denmark. RESULTS: A potential for increasing the reliability
      and validity of the data existed. Routines for monitoring other oral diseases
      than caries were limited. Compared with the other Scandinavian countries, the
      data collection system in Denmark appeared more functional and had adopted more
      modern concepts of disease management than other systems. In the light of modern
      concepts of caries management, data collected elsewhere had limited utility.
      CONCLUSIONS: The Scandinavian systems of health reporting had much in common, but
      some essential differences existed. If the quality of epidemiological data were
      enhanced, it would be possible to use the data for planning oral health care.
      Routines and procedures should be improved and updated in accordance with the
      modern ideas about caries prevention and therapy. For appropriate oral health
      planning in an organised dental service, reporting of enamel caries is essential.

PMID- 24885244
TI  - Incidence and outcome for patients with occult lymph node involvement in T1 and
      T2 oral squamous cell carcinoma: a prospective study.
AB  - BACKGROUND: The evidence base to inform the decision making process in patients
      with early stage oral cancer and a clinical and radiological N0 neck remains
      insufficient to answer the question when it is safe to "watch and wait" and when
      to proceed with a selective neck dissection. METHODS: A total of 327 consecutive
      cases of histopathologically staged T1-2, N0-1 and M0, but clinically N0,
      squamous cell carcinoma of the tongue were prospectively analysed. Univariate and
      multivariate analyses were used for statistical analysis and are represented as
      Kaplan-Meier analyses or Cox proportional hazard regression analysis. RESULTS: In
      61 patients (18.65%) lymph node involvement was found in the histopathological
      processing. The mean survival of all patients was 73.3 +/- 48.6 months. The 2
      year and 5-year overall survival rates of all patients were 87.5% and 68.4%,
      respectively. The 2-year and 5-year survival rates for stage N0 were 89.1% and
      70.7% compared to 83.3% and 62.9% in N1 situations. The 2-year and 5-year
      survival rates for stage T1 were 87.9% and 73.6% compared to 87.2% and 65.3% in
      stage T2, respectively. The time to recurrence in stage N0 was 35.1 +/- 30.5
      months compared to 25.63 +/- 24.6 months in cases with N1 disease. Stage T1 was
      associated with a time to recurrence of 38.1 +/- 33.9 months compared with 27.2
      +/- 22.7 months in patients classified T2.Variables found to be strongly
      associated with survival in the univariate analysis included older age, higher
      tumour and N stage, and grading. Age, tumour stage (p = 0.011, 95% CI, 1.09 to
      2.0), nodal stage (p = 0.038, 95% CI, 1.02 to 2.07), and recurrence were
      independently and significantly associated with survival in the multivariate
      analysis. CONCLUSIONS: This confirms a high overall disease free survival for
      patients with T1 and N0 treated with single modality surgery and in common with
      the literature confirms the poor impact on prognosis of the N positive neck.

PMID- 24885245
TI  - Fish-based remedies in Spanish ethnomedicine: a review from a historical
      perspective.
AB  - BACKGROUND: Fish-based therapeutics is fundamentally based on a dietary use, but
      these vertebrates have also been employed in the treatment of infectious and
      parasitic diseases, during pregnancy, childbirth and postpartum and to deal with
      diseases of the different systems. METHODS: An overview of the ethnomedical and
      historical Spanish literature has been carried out. Automated searches in the
      most important national and international databases have been performed. All
      related works have been thorough examined. RESULTS: We examine the historical use
      of 54 medicinal fish species, 48 marine and six from inland waters. As useful, in
      Ancient times 39 species have been recorded (of which only 21 have been collected
      in subsequent periods), seven in the Middle Ages, 18 in Modern times and 17 in
      the contemporary period. Anguilla anguilla, Engraulis encrasicolus or
      Scyliorhinus canicula are species that have survived over time as an ingredient
      in Spanish folk remedies. Most remedies used in the last century and currently
      are empirical remedies based on the humorism theory and the principle of
      contraria contrariis curantur (74%), and the rest (26%) are magical type remedies
      that complete the popular therapeutic arsenal. CONCLUSIONS: In the last century
      we find a progressive decrease in the number of fish species used in
      ethnomedicine. Only seven taxa have been documented as surviving therapeutic
      resources since centuries ago. The existence of a dynamic Spanish ethnomedicine
      has also been detected which has managed to generate new therapeutic resources in
      recent times. It is important to validate the remedies by ethnopharmacology and
      evidence-based medicine. In order to recover as much data as possible, it will be
      necessary to draw up an inventory of ethnoichthyological uses.

PMID- 24885247
TI  - Incidence and consequence of acute kidney injury in unselected emergency
      admissions to a large acute UK hospital trust.
AB  - BACKGROUND: AKI is common among hospital in-patients and places a huge financial
      burden on the UK National Health Service, causing increased length of hospital
      stay and use of critical care services, with increased requirement for complex
      interventions including dialysis. This may account for up to 0.6% of the total
      Health Service budget. To investigate the incidence and consequences of AKI, all
      unselected emergency admissions to a large acute UK single centre University
      Teaching Hospital over two separate 7 day periods were reviewed. METHODS: A
      retrospective audit of 745 case records was undertaken (54.6% male) including
      laboratory data post-discharge or death, with classification of AKI by RIFLE,
      AKIN and AKIB criteria. Participants were included whether admitted via their
      general practitioners, the emergency department, or as tertiary specialty
      transfers. Outcome measures were presence or absence of AKI recorded using each
      of the three AKI criteria, length of hospital stay (LOS), admission to, and LOS
      in critical care, and mortality. The most severe grade of AKI only, at any time
      during the admission, was recorded to prevent double counting. Renal outcome was
      determined by requirement for renal replacement therapy (RRT), and whether those
      receiving RRT remained dialysis dependent or not. RESULTS: AKI incidence was
      25.4% overall. With approximately one third present on admission and two thirds
      developing post admission. The AKI group had LOS almost three times higher than
      the non AKI group (10 vs 4 days). Requirement for critical care beds was 8.1% in
      the AKI group compared to 1.7% in non AKI group. Overall mortality was 5.5%, with
      the AKI group at 11.4% versus 3.3% in the non AKI group. CONCLUSIONS: AKI in
      acute unselected hospital admissions is more common than existing literature
      suggests, affecting 25% of unselected admissions. In many this is relatively mild
      and may resolve spontaneously, but is associated with increased LOS, likelihood
      of admission to critical care, and risk of death. If targeted effective
      interventions can be developed it seems likely that substantial clinical benefits
      for the patient, as well as financial and structural benefits for the healthcare
      organisation may accrue.

PMID- 24885248
TI  - Transcultural adaptation and validation of the "Hip and Knee" questionnaire into
      Spanish.
AB  - BACKGROUND: The purpose of the present study is to translate and validate the
      "Hip and Knee Outcomes Questionnaire", developed in English, into Spanish. The
      'Hip and Knee Outcomes Questionnaire is a questionnaire planned to evaluate the
      impact in quality of life of any problem related to the human musculoskeletal
      system. 10 scientific associations developed it. METHODS: The questionnaire
      underwent a validated translation/retro-translation process. Patients undergoing
      primary knee arthroplasty, before and six months postoperative, tested the final
      version in Spanish. Psychometric properties of feasibility, reliability, validity
      and sensitivity to change were assessed. Convergent validity with SF-36 and WOMAC
      questionnaires was evaluated. RESULTS: 316 patients were included. Feasibility: a
      high number of missing items in questions 3, 4 and 5 were observed. The number of
      patients with a missing item was 171 (51.35%) in the preoperative visit and 139
      (44.0%) at the postoperative. Internal validity: revision of coefficients in the
      item-rest correlation recommended removing question 6 during the preoperative
      visit (coefficient <0.20). Convergent validity: coefficients of correlation with
      WOMAC and SF-36 scales confirm the questionnaire's validity. Sensitivity to
      change: statistically significant differences were found between the mean scores
      of the first visit compared to the postoperative. CONCLUSION: The proposed
      translation to Spanish of the 'Hip and Knee Questionnaire' is found to be
      reliable, valid and sensible to changes produced at the clinical practice of
      patients undergoing primary knee arthroplasty. However, some changes at the
      completion instructions are recommended. LEVEL OF EVIDENCE: Level I. Prognostic
      study.

PMID- 24885249
TI  - Cloning, expression and biochemical characterization of the cholesterol oxidase
      CgChoA from Chryseobacterium gleum.
AB  - BACKGROUND: Cholesterol oxidases are important enzymes for applications such as
      the analysis of cholesterol in clinical samples, the synthesis of steroid derived
      drugs, and are considered as potential antibacterial drug targets. RESULTS: The
      gene choA encoding a cholesterol oxidase from Chryseobacterium gleum DSM 16776
      was cloned into the pQE-30 expression vector and heterologously expressed in
      Escherichia coli JM109 co-transformed with pRARE2. The N-terminally His-tagged
      cholesterol oxidase (CgChoA) was assigned to be a monomer in solution by size
      exclusion chromatography, showed a temperature optimum of 35 degrees C, and a pH
      optimum at 6.75 using 0.011 M MOPS buffer under the tested conditions. The
      purified protein showed a maximum activity of 15.5 U/mg. CgChoA showed a
      Michaelis-Menten like kinetic behavior only when the substrate was dissolved in
      water and taurocholate (apparent K(m) = 0.5 mM). In addition, the conversion of
      cholesterol by CgChoA was studied via biocatalytic batches at analytical scale,
      and cholest-4-en-3-one was confirmed as product by HPLC-MS. CONCLUSION: CgChoA is
      a true cholesterol oxidase which activity ranges among the high performing
      described cholesterol oxidases from other organisms. Thus, the enzyme broadens
      the available toolbox of cholesterol oxidases for e.g. synthetic and biosensing
      applications.

PMID- 24885250
TI  - Does physical activity prevent cognitive decline and dementia?: A systematic
      review and meta-analysis of longitudinal studies.
AB  - BACKGROUND: By 2050, it has been estimated that approximately one-fifth of the
      population will be made up of older adults (aged >=60 years). Old age often comes
      with cognitive decline and dementia. Physical activity may prevent cognitive
      decline and dementia. METHODS: We reviewed and synthesised prospective studies
      into physical activity and cognitive decline, and physical activity and dementia,
      published until January 2014. Forty-seven cohorts, derived from two previous
      systematic reviews and an updated database search, were used in the meta
      analyses. Included participants were aged >=40 years, in good health and/or
      randomly selected from the community. Studies were assessed for methodological
      quality. RESULTS: Twenty-one cohorts on physical activity and cognitive decline
      and twenty-six cohorts on physical activity and dementia were included. Meta
      analysis, using the quality-effects model, suggests that participants with higher
      levels of physical activity, when compared to those with lower levels, are at
      reduced risk of cognitive decline, RR 0.65, 95% CI 0.55-0.76, and dementia, RR
      0.86, 95% CI 0.76-0.97. Sensitivity analyses revealed a more conservative
      estimate of the impact of physical activity on cognitive decline and dementia for
      high quality studies, studies reporting effect sizes as ORs, greater number of
      adjustments (>=10), and longer follow-up time (>=10 years). When one heavily
      weighted study was excluded, physical activity was associated with an 18%
      reduction in the risk of dementia (RR 0.82; 0.73-0.91). CONCLUSIONS: Longitudinal
      observational studies show an association between higher levels of physical
      activity and a reduced risk of cognitive decline and dementia. A case can be made
      for a causal interpretation. Future research should use objective measures of
      physical activity, adjust for the full range of confounders and have adequate
      follow-up length. Ideally, randomised controlled trials will be conducted.
      Regardless of any effect on cognition, physical activity should be encouraged, as
      it has been shown to be beneficial on numerous levels.

PMID- 24885251
TI  - Birth weight and the risk of atrial fibrillation in whites and African Americans:
      the Atherosclerosis Risk In Communities (ARIC) study.
AB  - BACKGROUND: Low birth weight (LBW) has been associated with an increased risk of
      cardiovascular disease (CVD). A previous study, however, found higher risk of
      atrial fibrillation (AF) in individuals with higher birth weight (BW). To further
      understand this apparent paradox, we examined the relationship between AF and BW
      in the Atherosclerosis Risk in Communities (ARIC) cohort. METHODS: The analysis
      included 10,132 individuals free of AF at baseline (1996-1998), who provided BW
      information, were not born premature, and were not a twin. Self-reported BW was
      categorized as low (<2.5 kg), medium (2.5-4 kg), and high (>4.0 kg). AF incidence
      was ascertained from hospital discharge codes and death certificates. We used
      multivariable Cox proportional hazard models to determine the hazard ratios (HR)
      and 95% confidence intervals (CI) of AF across BW groups. RESULTS: During an
      average follow-up of 10.3 years, we identified 882 incident AF cases. LBW was
      associated with higher risk of AF. Compared to individuals in the medium BW
      category, the HR (95% CI) of AF was 1.33 (0.99, 1.78) for LBW and 1.00 (0.81,
      1.24) for high BW after adjusting for sociodemographic variables (p for trend =
      0.29). Additional adjustment for CVD risk factors did not attenuate the
      associations (HR 1.42, 95% CI 1.06, 1.90 for LBW and HR 0.86, 95% CI 0.69-1.07
      for high BW, compared to medium BW, p for trend = 0.01). CONCLUSION: LBW was
      associated with a higher risk of AF. This association was independent of known
      predictors of AF and is consistent with that observed for other cardiovascular
      diseases.

PMID- 24885252
TI  - Pro-osteogenic effects of fibrin glue in treatment of avascular necrosis of the
      femoral head in vivo by hepatocyte growth factor-transgenic mesenchymal stem
      cells.
AB  - BACKGROUND: Autologous transplantation of modified mesenchymal stem cells (MSCs)
      is a promising candidate for the treatment of the refractory clinical disease,
      avascular necrosis of the femoral head (ANFH). Our previous attempts by
      compounding MSCs with medical fibrin glue to treat ANFH in animal model have
      achieved excellent effects. However, the underlying molecular mechanism is
      unclear, especially on the transgenic gene expression. METHODS: Rabbit MSCs were
      isolated and compounded with fibrin glue. Following degrading of fibrin glue,
      proliferation, viability, expression of transgenic hepatocyte growth factor gene
      as well as osteogenic differentiation of MSCs were evaluated together with that
      of uncompounded MSCs. Fibrin glue-compounded MSCs were transplanted into the
      lesion of ANFH model, and the therapeutic efficacy was compared with uncompounded
      MSCs. One-Way ANOVA was used to determine the statistical significance among
      treatment groups. RESULTS: Fibrin glue compounding will not affect molecular
      activities of MSCs, including hepatocyte growth factor (HGF) secretion, cell
      proliferation and viability, and osteogenic differentiation in vitro. When
      applying fibrin glue-compounded MSCs for the therapy of ANFH in vivo, fibrin glue
      functioned as a drug delivery system and provided a sustaining microenvironment
      for MSCs which helped the relatively long-term secretion of HGF in the femoral
      head lesion and resulted in improved therapeutic efficacy when compared with
      uncompounded MSCs as indicated by hematoxylin-eosin staining and
      immunohistochemistry of osteocalcin, CD105 and HGF. CONCLUSION: Transplantation
      of fibrin glue-compounding MSCs is a promising novel method for ANFH therapy.

PMID- 24885253
TI  - Drug-repurposing identified the combination of Trolox C and Cytisine for the
      treatment of type 2 diabetes.
AB  - BACKGROUND: Drug-induced gene expression dataset (for example Connectivity Map,
      CMap) represent a valuable resource for drug-repurposing, a class of methods for
      identifying novel indications for approved drugs. Recently, CMap-based methods
      have successfully applied to identifying drugs for a number of diseases. However,
      currently few gene expression based methods are available for the repurposing of
      combined drugs. Increasing evidence has shown that the combination of drugs may
      valid for novel indications. METHOD: Here, for this purpose, we presented a
      simple CMap-based scoring system to predict novel indications for the combination
      of two drugs. We then confirmed the effectiveness of the predicted drug
      combination in an animal model of type 2 diabetes. RESULTS: We applied the
      presented scoring system to type 2 diabetes and identified a candidate
      combination of two drugs, Trolox C and Cytisine. Finally, we confirmed that the
      predicted combined drugs are effective for the treatment of type 2 diabetes.
      CONCLUSION: The presented scoring system represents one novel method for drug
      repurposing, which would provide helps for greatly extended the space of drugs.

PMID- 24885254
TI  - Pituitary metastasis of rhabdomyosarcoma: a case report and review of the
      literature.
AB  - INTRODUCTION: The pituitary gland is an uncommon site for metastases, in
      particular from rhabdomyosarcoma. Some authors have reported a recent increase in
      the incidence of metastases at infrequent sites, such as brain or bone, probably
      due to the expanded treatment options and the resulting improved survival.
      Treatment options are limited, but must be discussed and adapted to the patient
      profile. CASE PRESENTATION: We report the case of a 17-year-old Arabic man,
      diagnosed with alveolar rhabdomyosarcoma of the left shoulder, who, after several
      cycles of chemotherapy, presented symptoms and signs of pituitary dysfunction. To
      the best of our knowledge, it is the first case described. CONCLUSIONS: Pituitary
      metastasis of rhabdomyosarcoma is a rare situation, which must be actively
      researched to have access to an optimal therapeutic approach.

PMID- 24885255
TI  - Analysis of neuroretinal rim distribution and vascular pattern in eyes with
      presumed large physiological cupping: a comparative study.
AB  - BACKGROUND: To investigate possible differences in neuroretinal rim distribution,
      vascular pattern, and peripapillary region appearance between eyes with presumed
      large physiological optic disc cupping (pLPC) and eyes with minimal optic disc
      excavation. METHODS: We prospectively enrolled consecutive subjects with pLPC and
      individuals with minimal excavation (optic disc excavation within normal limits;
      control group). All eyes had normal visual fields and untreated intraocular
      pressure (IOP) <21 mmHg. Eyes with pLPC required vertical cup-to-disc ratio
      (VCDR) >= 0.6 and >= 30 months of follow-up with no evidence of glaucomatous
      neuropathy. For controls, VCDR was limited to <= 0.5. We compared ocular signs
      and characteristics related to the neuroretinal rim distribution, vascular
      pattern, peripapillary region appearance and disc size between groups. Whenever
      both eyes were eligible, one was randomly selected for analysis. RESULTS: A total
      of 74 patients (mean age, 45.6 +/- 14.9 years) with pLPC and 45 controls (mean
      age, 44.8 +/- 11.6 years) were enrolled (p = 0.76). Median disc size and VCDR was
      significantly larger in eyes with pLPC compared to controls (p < 0.01). The
      proportion of eyes with violation of the ISNT rule, laminar dot sign, nasal
      shifting of the central vessels, nasal excavation and baring of circumlinear
      vessel was significantly greater in the eyes with pLPC compared to controls (p <
      0.01). There were no significant differences regarding the proportions of eyes
      with peripapillary atrophy between groups (p < 0.09). Finally, disc size was
      significantly associated with VCDR (r(2) = 0.47, p < 0.01), with an increase of
      0.21 in VCDR for each 1 mm(2) in disc area. CONCLUSION: Compared to normal
      controls, eyes with pLPC may present a higher proportion of optic nerve head
      findings frequently observed in glaucomatous eyes. This seems to be explained in
      part by the larger discs found in these eyes. We believe care should be taken
      while classifying them as glaucomatous or not based solely on these
      characteristics.

PMID- 24885256
TI  - Workplace cluster of Bell's palsy in Lima, Peru.
AB  - BACKGROUND: We report on a workplace cluster of Bell's palsy that occurred within
      a four-month period in 2011 among employees of a three-story office building in
      Lima, Peru and our investigation to determine the etiology and associated risk
      factors. FINDINGS: An outbreak investigation was conducted to identify possible
      common infectious or environmental exposures and included patient interviews,
      reviews of medical records, an epidemiologic survey, serological analysis for IgM
      and IgG antibodies to putative Bell's palsy-inducing pathogens, and an
      environmental exposure assessment of the office building. Three cases of Bell's
      palsy were reported among 65 at-risk employees, attack rate 4.6%. Although two
      patients had underlying risk factors, there was no clear association or common
      identifiable risk factor among all cases. Serologic analysis showed no evidence
      of recent infections, and air and water sample measures of all known chemical or
      neurotoxins were below maximum allowable concentrations for exposure.
      CONCLUSIONS: An infection spread among workplace employees could not be excluded
      as a potential cause of this cluster; however, it was unlikely a pathogen
      commonly associated with individual cases of Bell's palsy. Although a specific
      etiology was not identified among all cases, we believe this methodology will aid
      future outbreak investigations of Bell's palsy and a better understanding of its
      etiology. While environmental assessments may be useful in their ability to
      ascertain the cause of clusters of Bell's palsy, future investigations should
      prioritize focus on common infectious etiology.

PMID- 24885257
TI  - FAP-alpha (Fibroblast activation protein-alpha) is involved in the control of
      human breast cancer cell line growth and motility via the FAK pathway.
AB  - BACKGROUND: Fibroblast Activation Protein alpha (FAP-alpha) or seprase is an
      integral membrane serine peptidase. Previous work has not satisfactorily
      explained both the suppression and promotion effects that have been observed in
      cancer. The purpose of this work was to investigate the role of FAP-alpha in
      human breast cancer. Expression of FAP-alpha was characterized in primary tumour
      samples and in cell lines, along with the effects of FAP-alpha expression on in
      vitro growth, invasion, attachment and migration. Furthermore the potential
      interaction of FAP-alpha with other signalling pathways was investigated.
      RESULTS: FAP-alpha was significantly increased in patients with poor outcome and
      survival. In vitro results showed that breast cancer cells over expressing FAP
      alpha had increased growth ability and impaired migratory ability. The growth of
      MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and
      MDA-MB-231 cells were not dramatically influenced by FAP-alpha expression. Over
      expression of FAP-alpha resulted in a reduction of phosphorylated focal adhesion
      kinase (FAK) level in both cells cultured in normal media and serum-free media.
      An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells
      and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels.
      However, inhibitors to PI3K, ERK, PLCUpsilon, NWASP, ARP2/3, and ROCK had no
      influence this. CONCLUSIONS: FAP-alpha in significantly associated with poor
      outcome in patients with breast cancer. In vitro, FAP-alpha promotes
      proliferation and inhibits migration of breast cancer cells, potentially by
      regulating the FAK pathway. These results suggest FAP-alpha could be a target for
      future therapies.

PMID- 24885258
TI  - The SystHERs registry: an observational cohort study of treatment patterns and
      outcomes in patients with human epidermal growth factor receptor 2-positive
      metastatic breast cancer.
AB  - BACKGROUND: Amplification of the human epidermal growth factor receptor 2 (HER2)
      gene occurs in approximately 20% of invasive breast cancer cases and is
      associated with a more aggressive disease course than HER2-negative breast
      cancer. HER2-targeted therapies have altered the natural history of HER2-positive
      breast cancer, a trend that will likely further improve with the recent approval
      of new agents. A prospective, observational cohort study was designed and
      initiated to provide real-world insights into current treatment patterns, long
      term survival, and patients' experiences with initial and subsequent treatments
      for HER2-positive metastatic breast cancer (MBC). METHODS/DESIGN: The Systematic
      Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs) is a US
      based prospective observational cohort study enrolling patients >=18 years of age
      with recently diagnosed HER2-positive MBC not previously treated with systemic
      therapy in the metastatic setting. The primary objective of the study is to
      identify treatment patterns and clinical outcomes in recently diagnosed patients
      in a variety of practice settings. Secondary objectives include comparative
      efficacy, safety, and patient-reported outcomes (PROs). Healthcare resource
      utilization is an exploratory end point. Tumor tissue and blood sample collection
      is optional.The SystHERs registry will enroll approximately 1000 patients over a
      3-year period, after which the study will continue for >=5 years, allowing for a
      maximum follow-up of 8 years. The treating physician will determine all care and
      the frequency of visits. PRO measures will be completed at study enrollment and
      every 90 days. Clinical data will be abstracted quarterly from patient records.
      The first patient was enrolled in June 2012, and preliminary descriptive data
      based on 25% to 30% of the final study population are expected at the end of
      2013, and as of April 25, 2014, 386 patients are enrolled. DISCUSSION: SystHERs
      is expected to provide in-depth data on demographic, clinicopathological, and
      treatment patterns and their associations with clinical outcomes, PROs, and
      healthcare resource utilization. Tumor tissue and DNA repositories will also be
      established for use in future translational research. TRIAL REGISTRATION NUMBER:
      NCT01615068 (ClinicalTrials.gov identifier).

PMID- 24885259
TI  - MiR-155 induction in microglial cells suppresses Japanese encephalitis virus
      replication and negatively modulates innate immune responses.
AB  - BACKGROUND: Microglial cells, which are resident macrophages of the central
      nervous system, play important roles in immune responses and pathogenesis.
      Japanese encephalitis virus (JEV) is a neurotropic virus that infects microglial
      cells in brain. Several microRNAs including miR-155 and miR-146a play an
      important role in defining the microglia inflammatory profile. In this study, we
      have investigated the effect of miR-155 and miR-146a modulation on JEV infection
      as well as innate immune responses in human microglial cells. METHODS: In vitro
      studies were performed in JEV-infected human microglial CHME3 cells. miR-155 or
      miR-146a were overexpressed and total RNA and protein were extracted following
      JEV-infection. Expression of genes involved in innate immune responses was
      studied by PCR array, quantitative real-time PCR (qPCR), western blot and
      Fluorescence activated cell sorter (FACS). JEV replication was monitored by
      studying the viral RNA by qPCR, protein by western blot, and titres by plaque
      assay. RESULTS: Overexpression of miR-155 in CHME3 cells resulted in
      significantly reduced JEV replication whereas miR-146a overexpression had an
      insignificant effect. Additionally, interferon regulatory factor 8 (IRF8) and
      complement factor H (CFH) were induced during JEV infection; however, this
      induction was attenuated in miR-155 overexpressing cells following JEV infection.
      Further, JEV-induced NF-kappaB regulated downstream gene expression was
      attenuated. Interestingly, an increased level of CD45, a negative regulator of
      microglia activation and a reduced phosphorylated-Signal Transducers and
      Activators of Transcription (p-STAT1) expression was observed in miR-155
      overexpressing cells upon JEV infection. CONCLUSION: Induction of miR-155 in
      human microglial cells may negatively modulate JEV-induced innate immune gene
      expression and may have a beneficial role in limiting JEV replication in human
      microglial cells.

PMID- 24885260
TI  - Determinant and outcome of early diagnosis of HIV infection among HIV-exposed
      infants in southwest Ethiopia.
AB  - BACKGROUND: Preventing mother-to-child transmission (PMTCT) of human
      immunodeficiency virus infection (HIV) has been a fundamental advancement in the
      acquired immunodeficiency syndrome (AIDS) response for the past decade. Several
      countries have made great strides in the efforts to prevent HIV through mother-to
      child transmission. The objective of this study is to assess the determinant and
      outcome of early diagnosis of HIV infection among HIV-exposed infants in
      southwest Ethiopia. METHODS: An institutional based retrospective cohort study
      was conducted in a hospital. Medical records of HIV-exposed infants and their
      mothers enrolled into the program were reviewed. Data entry and analysis was
      carried out using SPSS version 20 for Windows. RESULTS: A total of 426 HIV
      exposed infant-mother pairs where both mother and infants received a minimum ARV
      intervention for PMTCT were included in the study. Two hundred fifty-four (59.6%)
      of mothers had attended antenatal care (ANC). Of all participants, 234(54.9%)
      mothers did not receive any PMTCT prophylaxis during ANC, while only 104(24.4)
      received antiretroviral (ART) as PMTCT prophylaxis and 163(38.3%) claimed that
      did not observe any infant PMTCT interventions while 135(31.7%) of the infants
      received single-dose NVP + AZT. About 385(90.4%) infants were not infected at
      their final infection status. Those mothers who did not attended ANC follow-up,
      infants on mixed and complementary feeding and infants weaned off and mothers who
      were in WHO clinical stage III and IV were more likely to have HIV sero positive
      infant. CONCLUSION: This study showed that 385(90.4%) of the infants were not
      infected at their final infection status. Therefore, encouraging pregnant women
      to visit health facilities during their course of pregnancy, focusing on
      exclusive breast feeding counseling and promotion, and early initiation of
      antiretroviral treatment to HIV infected pregnant women are recommend.

PMID- 24885261
TI  - Behavioural and physiological adaptations to low-temperature environments in the
      common frog, Rana temporaria.
AB  - BACKGROUND: Extreme environments can impose strong ecological and evolutionary
      pressures at a local level. Ectotherms are particularly sensitive to low
      temperature environments, which can result in a reduced activity period, slowed
      physiological processes and increased exposure to sub-zero temperatures. The aim
      of this study was to assess the behavioural and physiological responses that
      facilitate survival in low-temperature environments. In particular, we asked: 1)
      do high-altitude common frog (Rana temporaria) adults extend the time available
      for larval growth by breeding at lower temperatures than low-altitude
      individuals?; and 2) do tadpoles sampled from high-altitude sites differ
      physiologically from those from low-altitude sites, in terms of routine metabolic
      rate (RMR) and freeze tolerance? Breeding date was assessed as the first day of
      spawn observation and local temperature recorded for five, paired high- and low
      altitude R. temporaria breeding sites in Scotland. Spawn was collected and
      tadpoles raised in a common laboratory environment, where RMR was measured as
      oxygen consumed using a closed respiratory tube system. Freeze tolerance was
      measured as survival following slow cooling to the point when all container water
      had frozen. RESULTS: We found that breeding did not occur below 5 degrees C at
      any site and there was no significant relationship between breeding temperature
      and altitude, leading to a delay in spawning of five days for every 100 m
      increase in altitude. The relationship between altitude and RMR varied by
      mountain but was lower for individuals sampled from high- than low-altitude sites
      within the three mountains with the highest high-altitude sites (>=900 m). In
      contrast, individuals sampled from low-altitudes survived freezing significantly
      better than those from high-altitudes, across all mountains. CONCLUSIONS: Our
      results suggest that adults at high-altitude do not show behavioural adaptations
      in terms of breeding at lower temperatures. However, tadpoles appear to have the
      potential to adapt physiologically to surviving at high-altitude via reduced RMR
      but without an increase in freeze tolerance. Therefore, survival at high-altitude
      may be facilitated by physiological mechanisms that permit faster growth rates,
      allowing completion of larval development within a shorter time period,
      alleviating the need for adaptations that extend the time available for larval
      growth.

PMID- 24885262
TI  - Study of bacterial adhesion on different glycopolymer surfaces by quartz crystal
      microbalance with dissipation.
AB  - Protein-carbohydrate interactions are involved in a wide variety of cellular
      recognition processes including cell growth regulation, differentiation and
      adhesion, the immune response, and viral or bacterial infections. A common way
      for bacteria to achieve adhesion is through their fimbriae which possess cellular
      lectins that can bind to complementary carbohydrates on the surface of the host
      tissues. In this work, we synthesized glycopolymers using reversible addition
      fragmentation chain transfer (RAFT) polymerization which were subsequently
      immobilized on a sensor surface for studies of bacterial adhesion by quartz
      crystal microbalance with dissipation (QCM-D). Ricinus communis Agglutinin
      (RCA120), a galactose specific lectin, was first studied by QCM-D to determine
      the specific lectin interactions to the different glycopolymers-treated surfaces.
      Subsequently, Pseudomonas aeruginosa PAO1 (a Gram-negative bacterium with
      galactose-specific binding C-type lectin (PA-IL)) and Escherichia coli K-12 (a
      Gram-negative bacterium with mannose-specific binding lectin) were then used as
      model bacteria to study bacterial adhesion mechanisms on different polymer
      treated sensor surfaces by the coupled resonance theory. Our results showed that
      lectin-carbohydrate interactions play significant roles in comparison to the
      nonspecific interactions, such as electrostatic interactions. A significantly
      higher amount of P. aeruginosa PAO1 could adhere on the glycopolymer surface with
      strong contact point stiffness as compared to E. coli K-12 on the same surface.
      Furthermore, in comparison to E. coli K-12, the adhesion of P. aeruginosa PAO1 to
      the glycopolymers was found to be highly dependent on the presence of calcium
      ions due to the specific C-type lectin interactions of PA-IL, and also the
      enhanced bacterial adhesion is attributed to the stiffer glycopolymer surface in
      higher ionic strength condition. 

PMID- 24885263
TI  - Fenretinide prevents inflammation and airway hyperresponsiveness in a mouse model
      of allergic asthma.
AB  - Arachidonic acid (AA) and docosahexaenoic acid (DHA) play important roles in
      inflammation and disease progression, where AA is viewed as proinflammatory and
      DHA as antiinflammatory. We observe in our model of allergic asthma that the
      AA/DHA ratio is significantly skewed in a proinflammatory direction. Fenretinide,
      a vitamin A derivative, has been shown to correct fatty acid imbalances in other
      diseases. Therefore, we explored if fenretinide can have a protective effect in
      allergic asthma. To accomplish this, we measured the levels of AA and DHA in the
      lungs of nonallergic, ovalbumin-induced allergic, and fenretinide-treated
      allergic mice. We also investigated the effect of allergic asthma and fenretinide
      treatment on markers of oxidative stress, levels of metabolites, IgE production,
      airway hyperresponsiveness, and histological changes. Our data demonstrate that
      treatment of allergen-sensitized mice with fenretinide before allergen challenge
      prevents ovalbumin-induced changes in the AA/DHA ratio. The levels of several
      metabolites, such as serotonin, and markers of cellular stress, which are
      increased after ovalbumin challenge, are also controlled by fenretinide
      treatment. We observed the protective effect of fenretinide against ovalbumin
      induced airway hyperresponsiveness and inflammation in the lungs, illustrated by
      a complete block in the infiltration of inflammatory cells to the airways and
      dramatically diminished goblet cell proliferation, even though IgE remained high.
      Our results demonstrate that fenretinide is an effective agent targeting
      inflammation, oxidation, and lung pathology observed in allergic asthma. 

PMID- 24885264
TI  - Differentiating cerebral ischemia from functional neurological symptom disorder:
      a psychosomatic perspective.
AB  - BACKGROUND: The differential diagnosis of pseudo-neurological symptoms often
      represents a clinical challenge. The Diagnostic and Statistical Manual of Mental
      Disorders, DSM-5, made an attempt to improve diagnostic criteria of conversion
      disorder (functional neurological symptom disorder). Incongruences of the
      neurological examination, i.e. positive neurological signs, indicate a new
      approach--whereas psychological factors are not necessary anymore. As the DSM-5
      will influence the International Classification of Diseases, ICD-11, this is of
      importance. In the case presented, a history of psychological distress and
      adverse childhood experiences coexisted with a true neurological disorder. We
      discuss the relevance of an interdisciplinary assessment and of operationalized
      diagnostic criteria. CASE PRESENTATION: A 32-year-old man presented twice with
      neurological symptoms without obvious pathological organic findings. A conversion
      disorder was considered early on at the second admission by the neurology team.
      Sticking to ICD-10, this diagnosis was not supported by a specialist for
      psychosomatic medicine, due to missing hints of concurrent psychological distress
      in temporal association with neurological symptoms. Further investigations then
      revealed a deep vein thrombosis (though D-dimers had been negative), which had
      probably resulted in a crossed embolus. CONCLUSION: The absence of a clear proof
      of biological dysfunction underlying neurological symptoms should not lead
      automatically to the diagnosis of a conversion disorder. In contrast, at least in
      more complex patients, the work-up should include repeated psychological and
      neurological assessments in close collaboration. According to ICD-10 positive
      signs of concurrent psychological distress are required, while DSM-5 emphasizes
      an incongruity between neurological symptoms and neurophysiological patterns of
      dysfunction. In the case presented, an extensive medical work-up was initially
      negative, and neither positive psychological nor positive neurological criteria
      could be identified. We conclude, that, even in times of more sophisticated
      operationalization of diagnostic criteria, the interdisciplinary assessment has
      to be based on an individual evaluation of all neurological and psychosocial
      findings. Prospective studies of inter-rater reliability and validity of
      psychological factors and positive neurological signs are needed, as evidence for
      both is limited. With respect to ICD-11, we suggest that positive neurological as
      well as psychological signs for functional neurological symptom disorder should
      be considered to increase diagnostic certainty.

PMID- 24885265
TI  - Are school-based mental health interventions for war-affected children effective
      and harmless?
AB  - In recent years, different approaches to large-scale mental health service
      provision for children in war-affected, mainly low- and middle-income, countries
      have been developed. Some school-based programs aiming at both strengthening
      resilience and reducing symptoms of trauma-related distress have been evaluated.
      In an article published in BMC Medicine, Tol and colleagues integrate their
      findings of the efficacy of universal school-based intervention across four
      countries and do not recommend classroom-based intervention as a treatment of
      trauma-related symptoms, since no consistent positive effects were found. On the
      contrary, for some children this type of universal intervention may impair
      recovery. Since universal school-based programs similar to the one evaluated here
      are widely implemented, Tol et al.'s results are highly relevant to inform the
      field of mental health service provision in war-affected countries.

PMID- 24885267
TI  - Femoral nerve block Intervention in Neck of Femur fracture (FINOF): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Hip fractures are very painful leading to lengthy hospital stays.
      Conventional methods of treating pain are limited. Non-steroidal anti
      inflammatories are relatively contraindicated and opioids have significant side
      effects.Regional anaesthesia holds promise but results from these techniques are
      inconsistent. Trials to date have been inconclusive with regard to which blocks
      to use and for how long. Interpatient variability remains a problem.
      METHODS/DESIGN: This is a single centre study conducted at Queen's Medical
      Centre, Nottingham; a large regional trauma centre in England. It is a pragmatic,
      parallel arm, randomized controlled trial. Sample size will be 150 participants
      (75 in each group). Randomization will be web-based, using computer generated
      concealed tables (service provided by Nottingham University Clinical Trials
      Unit). There is no blinding. Intervention will be a femoral nerve block (0.5
      mls/kg 0.25% levo-bupivacaine) followed by ropivacaine (0.2% 5 ml/hr-1) infused
      via a femoral nerve catheter until 48 hours post-surgery. The control group will
      receive standard care. Participants will be aged over 70 years, cognitively
      intact (abbreviated mental score of seven or more), able to provide informed
      consent, and admitted directly through the Emergency Department from their place
      of residence. Primary outcomes will be cumulative ambulation score (from day 1 to
      3 postoperatively) and cumulative dynamic pain scores (day 1 to 3
      postoperatively). Secondary outcomes will be cumulative dynamic pain score
      preoperatively, cumulative side effects, cumulative calorific and protein intake,
      EUROQOL EQ-5D score, length of stay, and rehabilitation outcome (measured by
      mobility score). DISCUSSION: Many studies have shown the effectiveness of
      regional blockade in neck of femur fractures, but the techniques used have
      varied. This study aims to identify whether early and continuous femoral nerve
      block can be effective in relieving pain and enhancing mobilization.Trial
      registration. TRIAL REGISTRATION: The trial is registered with the European
      clinical trials database Eudract ref: 2010-023871-25. (17/02/2011). ISRCTN:
      ISRCTN92946117. Registered 26 October 2012.

PMID- 24885266
TI  - Health care needs of cancer survivors in general practice: a systematic review.
AB  - BACKGROUND: The number of cancer survivors is increasing due to improved
      treatments. Consequently, general practitioners will treat more and more cancer
      survivors in the upcoming years. Only little is known about the care needs of
      these survivors and guidelines to support general practitioners in their
      treatment of these patients are lacking. The aim of this study was to gain
      insight in the health care needs of cancer survivors in general practice.
      METHODS: A systematic review on cancer survivors' general practice needs was
      conducted in PubMed, Embase and the Cochrane Library of Systematic Reviews.
      Eligible studies could be qualitative or quantitative studies examining cancer
      survivors' needs in general practice. Studies of adult survivors, with any cancer
      type, considered free of active disease and no longer receiving active treatment,
      were included. For each study a quality score was given using a form developed
      specifically for this study. Statements about survivors' general practice needs
      were collected and corresponding themes were grouped. RESULTS: Fifteen studies
      were included, of which twelve were qualitative. Most mentioned general practice
      needs were psychosocial needs, mainly being support received form the GP,
      followed by a need for help with medical issues, and a need for information on
      cancer, recovery, late treatment effects and on adjusting to life after
      treatment. CONCLUSIONS: Cancer survivors have different types of general practice
      needs that are currently not or insufficiently met. This review provides a
      starting point for the development of new guidelines for general practitioners to
      support in cancer survivorship.

PMID- 24885268
TI  - Determining the impacts of hospital cost-sharing on the uninsured near-poor
      households in Vietnam.
AB  - OBJECTIVES: The study objective was to identify the size of different hospital
      financing sources for different hospital services and their impact on the
      uninsured. METHODS: A panel dataset of 84 public general hospitals (2005-2008)
      with cross-section data on hospital activity and hospital revenue was created and
      used to calculate unit costs of different hospital services by applying multiple
      regression models. The resulting risk of catastrophic health expenditure (CHE)
      was estimated based on official income statistics. RESULTS: Average user fees
      (UF) for outpatient visits and inpatient bed days were US$4.13 and US$20.27,
      while actual full costs (AFC) were US$8.41 and US$36.66, respectively. These unit
      costs were 2.5 times higher in hospitals at the central versus the provincial
      level. UF for surgical inpatient bed days were 3.6 times that of non-surgical
      treatments (US$47.50 vs. 12.87) and AFC 5.0 times (US$101.72 vs. 20.08). UF
      accounted for 44.6%-77.9% of the AFC, the rest (22.1%-55.4%) was provided by
      direct government support (DGS). One surgical inpatient treatment at either
      central or provincial hospital level and one non-surgical inpatient treatment at
      central hospital level, immediately pushed uninsured near-poor households at risk
      of CHE. CONCLUSIONS: Around 45% of hospital AFC was paid by DGS, the larger rest
      by UF. UF have become a great financial burden on the uninsured near-poor
      households, who have to pay for these out-of-pocket and therefore may not utilize
      even necessary services. If the rate of DGS were reduced, this would have the
      effect of increasing UF, but the savings to Government could be spent on
      subsidizing insurance to ensure that a larger part of the population can cover UF
      through insurance, especially the near-poor households.

PMID- 24885269
TI  - Bronchial asthma is associated with increased risk of chronic kidney disease.
AB  - BACKGROUND: Bronchial asthma influences some chronic diseases such as coronary
      heart disease, diabetes mellitus, and hypertension, but the impact of asthma on
      vital diseases such as chronic kidney disease is not yet verified. This study
      aims to clarify the association between bronchial asthma and the risk of
      developing chronic kidney disease. METHODS: The National Health Research
      Institute provided a database of one million random subjects for the study. A
      random sample of 141 064 patients aged >=18 years without a history of kidney
      disease was obtained from the database. Among them, there were 35 086 with
      bronchial asthma and 105 258 without asthma matched for sex and age for a ration
      of 1:3. After adjusting for confounding risk factors, a Cox proportional hazards
      model was used to compare the risk of developing chronic kidney disease during a
      three-year follow-up period. RESULTS: Of the subjects with asthma, 2 196 (6.26%)
      developed chronic kidney disease compared to 4 120 (3.91%) of the control
      subjects. Cox proportional hazards regression analysis revealed that subjects
      with asthma were more likely to develop chronic kidney disease (hazard ratio
      [HR]: 1.56; 95% CI: 1.48-1.64; p < 0.001). After adjusting for sex, age, monthly
      income, urbanization level, geographic region, diabetes mellitus, hypertension,
      hyperlipidemia, and steroid use, the HR for asthma patients was 1.40 (95% CI:
      1.33-1.48; p = 0.040). There was decreased HRs in steroid use (HR: 0.56; 95% CI:
      0.62-0.61; p < 0.001) in the development of chronic kidney disease. Expectorants,
      bronchodilators, anti-muscarinic agents, airway smooth muscle relaxants, and
      leukotriene receptor antagonists may also be beneficial in attenuating the risk
      of chronic kidney disease. CONCLUSIONS: Patients with bronchial asthma may have
      increased risk of developing chronic kidney disease. The use of steroids or non
      steroidal drugs in the treatment of asthma may attenuate this risk.

PMID- 24885270
TI  - Generating genius: how an Alzheimer's drug became considered a 'cognitive
      enhancer' for healthy individuals.
AB  - BACKGROUND: Donepezil, an acetylcholinesterase inhibitor used in the treatment of
      Alzheimer's disease, has been widely cited in media and bioethics literature on
      cognitive enhancement (CE) as having the potential to improve the cognitive
      ability of healthy individuals. In both literatures, this claim has been
      repeatedly supported by the results of a small study published by Yesavage et al.
      in 2002 on non-demented pilots (30-70 years old). The factors contributing to
      this specific interpretation of this study's results are unclear. METHODS: We
      examined print media and interdisciplinary bioethics coverage of this small
      study, aiming to provide insight into how evidence from research may be shaped
      within different discourses, potentially influencing important policy, ethics,
      and clinical decisions. Systematic qualitative content analysis was used to
      examine how this study was reported in 27 media and 22 bioethics articles.
      Articles were analyzed for content related to: (1) headlines and titles; (2)
      colloquialisms; and, (3) accuracy of reporting of the characteristics and results
      of the study. RESULTS: In media and bioethics articles referencing this small
      study, strong claims were made about donepezil as a CE drug. The majority of
      headlines, titles, and colloquialisms used enhancement language and the majority
      of these suggest that donepezil could be used to enhance intellectual ability.
      Further, both literatures moved between reporting the results of the primary
      study and magnifying the perceived connection between these results and the CE
      debate that was alluded to in the primary study. Specific descriptions of the
      results overwhelmingly reported an improvement in performance on a flight
      simulator, while more general statements claimed donepezil enhanced cognitive
      performance. Further, a high level of reporting accuracy was found regarding
      study characteristics of the original study, but variable levels of accuracy
      surrounded the presentation of complex characteristics (i.e., methods) or
      contentious properties of the CE debate (i.e., initial health status of the study
      subjects). CONCLUSIONS: Hyped claims of CE effects cannot be completely accounted
      for by sheer inaccuracy in reporting. A complex interaction between the primary
      and secondary literature, and expectations and social pressures related to CE
      appears to drive enthusiastic reports.

PMID- 24885271
TI  - BicSPAM: flexible biclustering using sequential patterns.
AB  - BACKGROUND: Biclustering is a critical task for biomedical applications. Order
      preserving biclusters, submatrices where the values of rows induce the same
      linear ordering across columns, capture local regularities with constant,
      shifting, scaling and sequential assumptions. Additionally, biclustering
      approaches relying on pattern mining output deliver exhaustive solutions with an
      arbitrary number and positioning of biclusters. However, existing order
      preserving approaches suffer from robustness, scalability and/or flexibility
      issues. Additionally, they are not able to discover biclusters with symmetries
      and parameterizable levels of noise. RESULTS: We propose new biclustering
      algorithms to perform flexible, exhaustive and noise-tolerant biclustering based
      on sequential patterns (BicSPAM). Strategies are proposed to allow for symmetries
      and to seize efficiency gains from item-indexable properties and/or from
      partitioning methods with conservative distance guarantees. Results show BicSPAM
      ability to capture symmetries, handle planted noise, and scale in terms of memory
      and time. BicSPAM also achieves the best match-scores for the recovery of hidden
      biclusters in synthetic datasets with varying noise distributions and levels of
      missing values. Finally, results on gene expression data lead to complete
      solutions, delivering new biclusters corresponding to putative modules with
      heightened biological relevance. CONCLUSIONS: BicSPAM provides an exhaustive way
      to discover flexible structures of order-preserving biclusters. To the best of
      our knowledge, BicSPAM is the first attempt to deal with order-preserving
      biclusters that allow for symmetries and that are robust to varying levels of
      noise.

PMID- 24885272
TI  - Deciphering the mechanism behind Fibroblast Growth Factor (FGF) induced biphasic
      signal-response profiles.
AB  - BACKGROUND: The Fibroblast Growth Factor (FGF) pathway is driving various aspects
      of cellular responses in both normal and malignant cells. One interesting
      characteristic of this pathway is the biphasic nature of the cellular response to
      some FGF ligands like FGF2. Specifically, it has been shown that phenotypic
      behaviors controlled by FGF signaling, like migration and growth, reach maximal
      levels in response to intermediate concentrations, while high levels of FGF2
      elicit weak responses. The mechanisms leading to the observed biphasic response
      remains unexplained. RESULTS: A combination of experiments and computational
      modeling was used to understand the mechanism behind the observed biphasic
      signaling responses. FGF signaling involves a tertiary surface interaction that
      we captured with a computational model based on Ordinary Differential Equations
      (ODEs). It accounts for FGF2 binding to FGF receptors (FGFRs) and heparan sulfate
      glycosaminoglycans (HSGAGs), followed by receptor-phosphorylation, activation of
      the FRS2 adapter protein and the Ras-Raf signaling cascade. Quantitative protein
      assays were used to measure the dynamics of phosphorylated ERK (pERK) in response
      to a wide range of FGF2 ligand concentrations on a fine-grained time scale for
      the squamous cell lung cancer cell line H1703. We developed a novel approach
      combining Particle Swarm Optimization (PSO) and feature-based constraints in the
      objective function to calibrate the computational model to the experimental data.
      The model is validated using a series of extracellular and intracellular
      perturbation experiments. We demonstrate that in silico model predictions are in
      accordance with the observed in vitro results. CONCLUSIONS: Using a combined
      approach of computational modeling and experiments we found that competition
      between binding of the ligand FGF2 to HSGAG and FGF receptor leads to the
      biphasic response. At low to intermediate concentrations of FGF2 there are
      sufficient free FGF receptors available for the FGF2-HSGAG complex to enable the
      formation of the trimeric signaling unit. At high ligand concentrations the
      ligand binding sites of the receptor become saturated and the trimeric signaling
      unit cannot be formed. This insight into the pathway is an important
      consideration for the pharmacological inhibition of this pathway.

PMID- 24885273
TI  - Association between STAT3 gene polymorphisms and Crohn's disease susceptibility:
      a case-control study in a Chinese Han population.
AB  - BACKGROUND: Crohn's disease (CD) is an immune-related disease with genetic
      predisposition. This study aimed to investigate the association of three
      polymorphisms in the signal transducer and activator of transcription 3 (STAT3)
      gene with CD risk in a Chinese population. METHODS: We conducted a hospital-based
      case-control study involving 232 CD patients and 272 controls. Genotyping was
      performed using polymerase chain reaction with sequence-specific primer method.
      Statistical analyses were conducted using logistic regression and genotype risk
      scoring. RESULTS: Significant differences were found between patients and
      controls in allele/genotype distributions of rs744166 (Pallele=0.0008;
      Pgenotype=0.003) and allele distributions of rs4796793 (P = 0.03). The risk for
      CD associated with the rs744166-A mutant allele decreased by 37% [95% confidence
      interval (CI): 0.48-0.83] under the additive model, 39% (95% CI: 0.43-0.81) under
      the dominant model and 57% (95% CI: 0.24-0.77) under the recessive model.
      Carriers of the rs4796793-G mutant allele exhibited 25% (95% CI: 0.58-0.98;
      P=0.03) and 47% (95% CI: 0.30-0.95) decreased risks of developing CD under the
      additive and recessive models, respectively. CONCLUSIONS: STAT3 rs744166 and
      rs4796793 polymorphisms may be associated with CD occurrence and used as a
      predictive factor of CD in Chinese Han populations. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2169674321122294.

PMID- 24885274
TI  - Performance of seven serological assays for diagnosing tularemia.
AB  - BACKGROUND: Tularemia is a rare zoonotic disease caused by the Gram-negative
      bacterium Francisella tularensis. Serology is frequently the preferred diagnostic
      approach, because the pathogen is highly infectious and difficult to cultivate.
      The aim of this retrospective study was to determine the diagnostic accuracy of
      tularemia specific tests. METHODS: The Serazym(r)Anti-Francisella tularensis
      ELISA, Serion ELISA classic Francisella tularensis IgG/IgM, an in-house ELISA,
      the VIRapid(r) Tularemia immunochromatographic test, an in-house antigen
      microarray, and a Western Blot (WB) assay were evaluated. The diagnosis tularemia
      was established using a standard micro-agglutination assay. In total, 135 sera
      from a series of 110 consecutive tularemia patients were tested. RESULTS: The
      diagnostic sensitivity and diagnostic specificity of the tests were VIRapid
      (97.0% and 84.0%), Serion IgG (96.3% and 96.8%), Serion IgM (94.8% and 96.8%),
      Serazym (97.0% and 91.5%), in-house ELISA (95.6% and 76.6%), WB (93.3% and
      83.0%), microarray (91.1% and 97.9%). CONCLUSIONS: The diagnostic value of the
      commercial assays was proven, because the diagnostic accuracy was >90%. The
      diagnostic sensitivity of the in-house ELISA and the WB were acceptable, but the
      diagnostic accuracy was <90%. Interestingly, the antigen microarray test was very
      specific and had a very good positive predictive value.

PMID- 24885275
TI  - Predicting the fungal CUG codon translation with Bagheera.
AB  - BACKGROUND: Many eukaryotes have been shown to use alternative schemes to the
      universal genetic code. While most Saccharomycetes, including Saccharomyces
      cerevisiae, use the standard genetic code translating the CUG codon as leucine,
      some yeasts, including many but not all of the "Candida", translate the same
      codon as serine. It has been proposed that the change in codon identity was
      accomplished by an almost complete loss of the original CUG codons, making the
      CUG positions within the extant species highly discriminative for the one or
      other translation scheme. RESULTS: In order to improve the prediction of genes in
      yeast species by providing the correct CUG decoding scheme we implemented a web
      server, called Bagheera, that allows determining the most probable CUG codon
      translation for a given transcriptome or genome assembly based on extensive
      reference data. As reference data we use 2071 manually assembled and annotated
      sequences from 38 cytoskeletal and motor proteins belonging to 79 yeast species.
      The web service includes a pipeline, which starts with predicting and aligning
      homologous genes to the reference data. CUG codon positions within the predicted
      genes are analysed with respect to amino acid similarity and CUG codon
      conservation in related species. In addition, the tRNACAG gene is predicted in
      genomic data and compared to known leu-tRNACAG and ser-tRNACAG genes. Bagheera
      can also be used to evaluate any mRNA and protein sequence data with the codon
      usage of the respective species. The usage of the system has been demonstrated by
      analysing six genomes not included in the reference data. CONCLUSIONS: Gene
      prediction and consecutive comparison with reference data from other
      Saccharomycetes are sufficient to predict the most probable decoding scheme for
      CUG codons. This approach has been implemented into Bagheera
      (http://www.motorprotein.de/bagheera).

PMID- 24885276
TI  - Glenohumeral joint motion after subscapularis tendon repair: an analysis of
      cadaver shoulder models.
AB  - BACKGROUND: As for the surgical treatment of the rotator cuff tears, the
      subscapularis tendon tears have recently received much attention for the mini
      open or arthroscopic repair. The results of surgical repair for the subscapularis
      tendon tear are satisfactory, but the range of external rotation is reported to
      be restricted after the repair. The purpose of this study was to evaluate the
      range of glenohumeral joint motion after repairs of various sizes of
      subscapularis tendon tears. METHODS: Using eight fresh frozen human cadaveric
      shoulders (mean age at death, 81.5 years), three sizes of subscapularis tendon
      tear (small, medium, and large) were made and then repaired. With the scapula
      fixed to the wooden jig, the end-range of glenohumeral motion was measured with
      passive movement applied through 1.0-Nm torque in the directions of scapular
      elevation, flexion, abduction, extension, horizontal abduction, and horizontal
      adduction. The passive end-ranges of external and internal rotation in various
      positions with rotational torque of 1.0 Nm were also measured. Differences in the
      ranges among the three type tears were analyzed. RESULTS: As tear size increased,
      range of glenohumeral motion in horizontal abduction after repair decreased
      gradually and was significantly decreased with the large size tear (P < 0.01).
      The end-range of external rotation decreased progressively with increasing tear
      size in every glenohumeral position. The prominent decrease in external rotation
      (around 40 degrees  reduction from intact shoulders) was observed in shoulders
      after repair of large size tear at 30 degrees  to 60 degrees  of scapular
      elevation and abduction. CONCLUSIONS: As the size of the subscapularis tendon
      tear increased, the passive ranges of horizontal abduction and external rotation
      of the glenohumeral joint after repair decreased significantly. In shoulders with
      a subscapularis tendon tear, it is necessary to consider the reduction of
      external rotation depending on tear size.

PMID- 24885277
TI  - Cryptococcal meningitis presenting with bilateral complete ophthalmoplegia: a
      case report.
AB  - BACKGROUND: Cryptococcus neoformans is saprophytic encapsulated yeast. Infection
      is acquired by inhalation of the organism and could be asymptomatic or limited to
      the lungs, specially in the immunocompetent host. Cryptococcal meningitis is a
      serious opportunistic infection among post transplant recipients. Cranial nerve
      palsies and ophthalmoplegia are well known complications of this disease, but
      bilateral complete ophthalmoplegia is a very rare presentation. CASE
      PRESENTATION: A Sri Lankan young male, who is a post kidney transplant recipient,
      presented with bilateral complete ophthalmoplegia and subsequently was diagnosed
      to have cryptococcal meningitis based on Indian ink stain and culture of
      cerebrospinal fluid (CSF). His magnetic resonance imaging (MRI) showed bilateral
      multiple nodular lesions in both basal ganglia and thalami. Brainstem imaging was
      normal. CONCLUSIONS: Cryptococcal meningitis is a serious fungal infection in
      post transplant patients. It should be suspected in any immunocompromised patient
      with fever, headache and focal neurological signs. Bilateral thalamic lesions,
      inflammation and invasion of the cranial nerves and raised intracranial pressure
      were thought to be possible mechanisms resulting in bilateral complete
      ophthalmoplegia in this patient.

PMID- 24885278
TI  - Population attributable fraction of type 2 diabetes due to physical inactivity in
      adults: a systematic review.
AB  - BACKGROUND: Physical inactivity is a global pandemic. The population attributable
      fraction (PAF) of type 2 diabetes mellitus (T2DM) associated with physical
      inactivity ranges from 3% to 40%. The purpose of this systematic review was to
      determine the best estimate of PAF for T2DM attributable to physical inactivity
      and absence of sport participation or exercise for men and women. METHODS: We
      conducted a systematic review that included a comprehensive search of MEDLINE,
      EMBASE, SportDiscus, and CINAHL (1946 to April 30 2013) limited by the terms
      adults and English. Two reviewers screened studies, extracted PAF related data
      and assessed the quality of the selected studies. We reconstructed 95% CIs for
      studies missing these data using a substitution method. RESULTS: Of the eight
      studies reporting PAF in T2DM, two studies included prospective cohort studies (3
      total) and six were reviews. There were distinct variations in quality of
      defining and measuring physical inactivity, T2DM and adjusting for confounders.
      In the US, PAFs for absence of playing sport ranged from 13% (95% CI: 3, 22) in
      men and 29% (95% CI: 17, 41) in women. In Finland, PAFs for absence of exercise
      ranged from 3% (95% CI: -11, 16) in men to 7% (95% CI: -9, 20) in women.
      CONCLUSIONS: The PAF of physical inactivity due to T2DM is substantial. Physical
      inactivity is a modifiable risk factor for T2DM. The contribution of physical
      inactivity to T2DM differs by sex; PAF also differs if physical inactivity is
      defined as the absence of 'sport' or absence of 'exercise'.

PMID- 24885279
TI  - Role of the BaeSR two-component system in the regulation of Acinetobacter
      baumannii adeAB genes and its correlation with tigecycline susceptibility.
AB  - BACKGROUND: Tigecycline resistance in Acinetobacter baumannii is primarily
      acquired through overexpression of the AdeABC efflux pump. Besides AdeRS, other
      two-component regulatory systems (TCSs) involving the regulation of this
      transporter have not been clarified. RESULTS: In this study, we found that the
      TCS genes baeR and baeS are co-transcribed and function as stress responders
      under high osmotic conditions. The baeSR and adeAB genes showed increased
      transcription in both the laboratory-induced and clinical tigecycline-resistant
      strains compared with the wild-type strain. The deletion of baeR in the ATCC
      17978 strain led to 67-73% and 68% reduction in adeA and adeB expression,
      respectively, with a resultant 2-fold decrease in the tigecycline minimal
      inhibition concentration (MIC). In contrast, the overexpression of baeR resulted
      in a doubled tigecycline MIC, with a more than 2-fold increase in adeA and adeB
      expression. The influence of baeR knockout on adeAB gene expression can also be
      observed in the laboratory-induced tigecycline-resistant strain. A time-kill
      assay showed that the baeR deletion mutant showed an approximate 1-log10
      reduction in colony forming units (CFUs) relative to the wild-type strain when
      the tigecycline concentration was 0.25 MUg/mL throughout the assay period. The
      wild-type phenotype could be restored by trans-complementation with pWH1266-kanr
      baeR. Increasing the tigecycline concentration to 0.5 MUg/mL produced an even
      more marked 4.7-log10 reduction in CFUs of the baeR deletion mutant at 8 h, while
      only a 2.1-log10 reduction was observed for the wild-type strain. CONCLUSIONS:
      Taken together, these data show for the first time that the BaeSR TCS influences
      the tigecycline susceptibility of A. baumannii through the positive regulation of
      the resistance-nodulation-division efflux pump genes adeA and adeB.

PMID- 24885280
TI  - Health effects of indebtedness: a systematic review.
AB  - BACKGROUND: In the aftermath of the global financial crisis, millions of
      households have been left with debts that they are unable to manage. Indebtedness
      may impair the wellbeing of those affected by it for years to come. This
      systematic review focuses on the long-term consequences of indebtedness on
      health. METHODS: The method used in the paper is a systematic review. First,
      bibliographic databases were searched for peer-reviewed articles. Second, the
      references and citations of the included articles were searched for additional
      articles. RESULTS: The results from our sample of 33 peer-reviewed studies
      demonstrate serious health effects related to indebtedness. Individuals with
      unmet loan payments had suicidal ideation and suffered from depression more often
      than those without such financial problems. Unpaid financial obligations were
      also related to poorer subjective health and health-related behaviour. Debt
      counselling and other programmes to mitigate debt-related stress are needed to
      alleviate the adverse effects of indebtedness on health. CONCLUSIONS: The results
      demonstrate that indebtedness has serious effects on health.

PMID- 24885281
TI  - The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons.
AB  - 6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling
      degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also
      causes axonal degeneration, a process that appears to precede the death of DA
      neurons. To understand the processes involved in 6-OHDA-mediated axonal
      degeneration, a microdevice designed to isolate axons fluidically from cell
      bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA
      neurons. Results showed that 6-OHDA quickly induced mitochondrial transport
      dysfunction in both DA and non-DA axons. This appeared to be a general effect on
      transport function since 6-OHDA also disrupted transport of synaptophysin-tagged
      vesicles. The effects of 6-OHDA on mitochondrial transport were blocked by the
      addition of the SOD1-mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride
      (MnTBAP), as well as the anti-oxidant N-acetyl-cysteine (NAC) suggesting that
      free radical species played a role in this process. Temporally, microtubule
      disruption and autophagy occurred after transport dysfunction yet before DA cell
      death following 6-OHDA treatment. The results from the study suggest that ROS
      mediated transport dysfunction occurs early and plays a significant role in
      inducing axonal degeneration in response to 6-OHDA treatment. 

PMID- 24885282
TI  - Sleep duration, snoring habits and risk of acute myocardial infarction in China
      population: results of the INTERHEART study.
AB  - BACKGROUND: Less sleep time and snoring have been associated with cardiovascular
      disease (CVD) risk in Western populations; however, few studies have evaluated
      the different aspects of sleep duration and snoring frequency in relation to CVD,
      and this association has not been examined in China. The present study aimed to
      address the relation between sleep duration, snoring frequency and risk of acute
      myocardial infarction (AMI) in China population. METHODS: We conducted a hospital
      based case-control study. Cases were first AMI (n = 2909). Controls were matched
      to cases on age and sex. 2947 controls who did not report previous angina or
      physical disability completed a questionnaire on sleep duration and snoring
      frequency. We used logistic regression to control for other risk factors.
      RESULTS: We observed an inverse association between serious snoring frequency and
      AMI risk. After adjustment for all the risk factors, and the OR for everyday
      group and 3-5 times per week group was 1.45 (95% CI: 1.01 to 1.91) and 1.93 (95%
      CI: 1.52-2.46) compared to no snoring group. The OR for serious level group and
      moderate group was 1.77 (95% CI: 1.29 to 2.43) and 1.37 (95% CI: 1.10 to 1.69)
      compared to no snoring group. People having serious snoring increased 77% risk of
      AMI. 15.2% people in control group have <= 6 hours sleeping, compared with 17.4%
      in AMI group. CONCLUSIONS: Snoring frequency, including as much as everyday and 3
      5 times per week, was positively associated with AMI risk and less sleep duration
      was associated with risk of AMI. Less sleep time could increase AMI risk in China
      population.

PMID- 24885283
TI  - Effects of the vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor
      SU5416 on in vitro cultures of Plasmodium falciparum.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is taken up by parasitized
      red blood cells during malaria and stimulates intra-erythrocytic growth of
      Plasmodium falciparum in vitro. The cause and consequence of this uptake is not
      understood. METHODS: Plasmodium falciparum was cultured in vitro. Parasite growth
      and intracellular VEGF levels were assessed using flow cytometry. Intracellular
      VEGF was visualized by fluorescence immunocytochemistry. Phosphorylated tyrosine
      was measured by western blotting. In vivo assessment of intra-erythrocytic VEGF
      was performed in Plasmodium berghei ANKA-infected C57BL/6 mice. RESULTS: VEGF
      accumulated intracellularly in infected red blood cells, particularly in
      schizonts. In vitro growth of P. falciparum was unchanged when co-cultured with
      the anti-VEGF antibody bevacizumab or with an anti-VEGF receptor-1 peptide. In
      contrast, the VEGF receptor-2 inhibitor, SU5416, dose-dependently inhibited
      growth. None of the treatments reduced intracellular VEGF levels. Thus, the anti
      parasitic effect of SU5416 seemed independent of VEGF uptake. SU5416 reduced
      phosphorylated tyrosine in parasitized red blood cells. Similarly, the broad
      spectrum tyrosine kinase inhibitor genistein dose-dependently inhibited P.
      falciparum growth and reduced tyrosine phosphorylation. Neither bevacizumab nor
      anti-VEGF receptor-1 peptide affected tyrosine kinase activity. Finally, in vivo
      uptake of VEGF in P. berghei ANKA was demonstrated, analogous to the in vitro
      uptake in P. falciparum, making it a possible model for the effects of VEGF
      signalling in vivo during malaria. CONCLUSIONS: Inhibition of VEGFR-2 signalling
      reduces intra-erythrocytic growth of P. falciparum, likely due to tyrosine kinase
      inhibition. Internalisation of VEGF in P. falciparum-infected red blood cells
      does not rely on VEGF receptors. The function of in vivo uptake of VEGF can be
      studied in rodent malaria models.

PMID- 24885284
TI  - Autochthonous Dirofilaria repens in Austria.
AB  - BACKGROUND: In Europe animal and human infections due to Dirofilaria repens are
      increasing. FINDINGS: In a nationwide screening for filarioid parasites in
      Austria, 7,632 mosquitoes were collected from June till October 2012 and divided
      into 437 pools according to same trapping date and sight and mosquito species.
      For the molecular detection, a real-time PCR approach was followed by
      conventional PCR. D. repens was detected in the villages Moerbisch and Rust,
      Burgenland in one Anopheles maculipennis group and one Anopheles algeriensis
      species pool, respectively. CONCLUSIONS: The geographical distribution of the two
      positive pools points to the invasion of D. repens from Eastern neighboring
      countries. The finding of D. repens in mosquito vectors suggests the occurrence
      of the causative agent for cutaneous dirofilariosis in Austria.

PMID- 24885285
TI  - Prevalence of faecal incontinence and its related factors among patients in a
      Malaysian academic setting.
AB  - BACKGROUND: Prevalence data is essential for planning of healthcare services. The
      prevalence of faecal incontinence (FI) varies worldwide, and in Malaysia is not
      known. We sought to estimate its prevalence among patients with various
      conditions in a Malaysian academic setting. METHOD: A questionnaire-based survey
      was conducted among a convenience sample of adult patients and relatives who
      visited the Obstetrics and Gynaecology and General Surgery Clinics of University
      of Malaya Medical Centre (UMMC) from June 2009 to February 2010. Data collected
      included patient demographics and pre-existing medical conditions known to be FI
      risk factors. Severity of FI was assessed using the Wexner Continence Scale
      (WCS). RESULTS: Among the 1000 subjects recruited into the study, 760 (76%) were
      female and the median age was 38 years with an inter-quartile range of 24 years.
      The prevalence of FI among the study subjects was found to be 8.3%. Among them,
      63 subjects (75.9%) were determined to have mild FI as measured by the WCS. The
      proportions of patients with moderate and severe FI were 18.3% and 6.0%,
      respectively. FI was found to be significantly associated with older age,
      presence of diabetes mellitus and increased duration of defaecation. There was no
      statistically significant association between FI and sex, defaecation frequency,
      or history of surgery. CONCLUSION: FI in our setting is prevalent enough to
      warrant targeted healthcare interventions, including the need to improve general
      public awareness of the condition in order to counter social stigma and
      embarrassment that may be faced by patients.

PMID- 24885286
TI  - Determinants of high sensitivity cardiac troponin T elevation in acute ischemic
      stroke.
AB  - BACKGROUND: A proportion of patients with acute ischemic stroke have elevated
      cardiac troponin levels and ECG changes suggestive of cardiac injury, but the
      etiology is unclear. The aims of this study were to assess the frequency of high
      sensitivity cardiac troponin T (hs-cTnT) elevation, to identify determinants and
      ECG changes associated with hs-cTnT elevation, to identify patients with
      myocardial ischemia and to assess the impact of hs-cTnT elevation on in-hospital
      mortality. METHODS: Patients discharged with a diagnosis of acute ischemic stroke
      during a 1-year period, were included. Patients diagnosed with acute myocardial
      infarction (MI) within the last 7 days before admission or during hospitalization
      were excluded. RESULTS: In all, 156 (54.4%) of 287 patients had elevated hs-cTnT.
      The factors independently associated with hs-cTnT elevation were age >= 76 years
      (OR 3.71 [95% CI 2.04-6.75]), previous coronary heart disease (CHD) (OR 2.61
      [1.23-5.53]), congestive heart failure (OR 4.26 [1.15-15.82]), diabetes mellitus
      (OR 4.02 [1.50-10.76]) and lower eGFR (OR 0.97 [0.95-0.98]). Of the 182 patients
      who had two hs-cTnT measurements, 12 (6.6%) had both a rise or fall of hs-cTnT
      with at least one elevated value, and ECG manifestations of myocardial ischemia,
      e.g. meeting the criteria of acute MI. Both dynamic relative change (p = 0.026)
      and absolute change (p = 0.032) in hs-cTnT were significantly associated with
      higher in-hospital mortality. CONCLUSIONS: Established CHD and cardiovascular
      risk factors are associated with hs-cTnT elevation. Acute MI is likely
      underdiagnosed in acute ischemic stroke patients. Dynamic changes in troponin
      levels seem to be related to poor short-term prognosis.

PMID- 24885287
TI  - Salvage brachytherapy in prostate local recurrence after radiation therapy:
      predicting factors for control and toxicity.
AB  - PURPOSE: To evaluate efficacy and toxicity after salvage brachytherapy (BT) in
      prostate local recurrence after radiation therapy. METHODS AND MATERIALS: Between
      1993 and 2007, we retrospectively analyzed 56 consecutively patients (pts)
      undergoing salvage brachytherapy. After local biopsy-proven recurrence, pts
      received 145 Gy LDR-BT (37 pts, 66%) or HDR-BT (19 pts, 34%) in different dose
      levels according to biological equivalent doses (BED(2 Gy)). By the time of
      salvage BT, only 15 pts (27%) received ADT. Univariate and multivariate analyses
      were performed to identify predictors of biochemical control and toxicities.
      Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were
      graded using Common Terminology Criteria for Adverse Events (CTCv3.0). RESULTS:
      Median follow-up after salvage BT was 48 months. The 5-year FFbF was 77%. HDR and
      LDR late grade 3 GU toxicities were observed in 21% and 24%. Late grade 3 GI
      toxicities were observed in 2% (HDR) and 2.7% (LDR). On univariate analysis, pre
      salvage prostate-specific antigen (PSA) > 10 ng/ml (p = 0.004), interval to
      relapse after initial treatment < 24 months (p = 0.004) and salvage HDR-BT doses
      BED(2 Gy) level < 227 Gy (p = 0.012) were significant in predicting biochemical
      failure. On Cox multivariate analysis, pre-salvage PSA, and time to relapse were
      significant in predicting biochemical failure. HDR-BT BED(2 Gy) (alpha/beta 1.5
      Gy) levels >= 227 (p = 0.013), and ADT (p = 0.049) were significant in predicting
      grade >= 2 urinary toxicity. CONCLUSIONS: Prostate BT is an effective salvage
      modality in some selected prostate local recurrence patients after radiation
      therapy. Even, we provide some potential predictors of biochemical control and
      toxicity for prostate salvage BT, further investigation is recommended.

PMID- 24885288
TI  - Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition
      by influencing SOX2 expression in colorectal carcinoma cells.
AB  - BACKGROUND: Colorectal carcinoma (CRC) is a major cause of cancer mortality. The
      aberrant expression of several microRNAs is associated with CRC progression;
      however, the molecular mechanisms underlying this phenomenon are unclear.
      METHODS: miR-638 and SRY-box 2 (SOX2) expression levels were detected in 36 tumor
      samples and their adjacent, non-tumor tissues from patients with CRC, as well as
      in 4 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). SOX2
      expression levels were detected in 90 tumor samples and their adjacent tissue
      using immunohistochemistry. Luciferase reporter and Western blot assays were used
      to validate SOX2 as a target gene of miR-638. The regulation of SOX2 expression
      by miR-638 was assessed using qRT-PCR and Western blot assays, and the effects of
      exogenous miR-638 and SOX2 on cell invasion and migration were evaluated in vitro
      using the HCT-116 and SW1116 CRC cell lines. RESULTS: We found that miR-638
      expression was differentially impaired in CRC specimens and dependent on tumor
      grade. The inhibition of miR-638 by an antagomiR promoted cell invasion and a
      mesenchymal-like transition (lamellipodium stretching increased and cell-cell
      contacts decreased, which was accompanied by the suppression of the epithelial
      cell marker ZO-1/E-cadherin and the upregulation of the mesenchymal cell marker
      vimentin). A reporter assay revealed that miR-638 repressed the luciferase
      activity of a reporter gene coupled to the 3'-untranslated region of SOX2. miR
      638 overexpression downregulated SOX2 expression, and miR-638 inhibition
      upregulated SOX2 expression. Moreover, miR-638 expression levels were correlated
      inversely with SOX2 mRNA levels in human CRC tissues. The RNAi-mediated knockdown
      of SOX2 phenocopied the invasion-inhibiting effect of miR-638; furthermore, SOX2
      overexpression blocked the miR-638-induced CRC cell transition to epithelial-like
      cells. CONCLUSIONS: These results demonstrate that the loss of miR-638 promotes
      invasion and a mesenchymal-like transition by directly targeting SOX2 in vitro.
      These findings define miR-638 as a new, invasion-associated tumor suppressor of
      CRC.

PMID- 24885289
TI  - The Impact of Intensive Reading Intervention on Level of Attention in Middle
      School Students.
AB  - The purpose of the study was to estimate the impact of reading intervention on
      ratings of student attention over time. We used extant data from a longitudinal
      randomized study of a response-based reading intervention to fit a multiple
      indicator, multilevel growth model. The sample at randomization was 54% male, 18%
      limited English proficient, 85% eligible for free or reduced-price lunch, 58%
      African American, and 32% Hispanic. Reading ability was measured by using the
      Woodcock-Johnson III Tests of Achievement. Attention was measured by using the
      Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Scale. Findings
      indicate that intensive, response-based reading intervention over 3 years
      improved reading achievement and behavioral attention in middle school struggling
      readers, with treatment directly affecting reading, which in turn influenced
      attention. In the business-as-usual condition, there was no relation between
      improved reading and attention. The results are consistent with a correlated
      liabilities model of comorbidity. The results do not align with the inattention
      as-cause hypothesis, which predicts that reading intervention should not affect
      attention. The findings do not support, but do not necessarily preclude, the
      phenocopy hypothesis. The results are especially pertinent for older students who
      may be inattentive partly because of years of struggling with reading. 

PMID- 24885290
TI  - The peach volatilome modularity is reflected at the genetic and environmental
      response levels in a QTL mapping population.
AB  - BACKGROUND: The improvement of fruit aroma is currently one of the most sought
      after objectives in peach breeding programs. To better characterize and assess
      the genetic potential for increasing aroma quality by breeding, a quantity trait
      locus (QTL) analysis approach was carried out in an F1 population segregating
      largely for fruit traits. RESULTS: Linkage maps were constructed using the IPSC
      peach 9 K Infinium (r) II array, rendering dense genetic maps, except in the case
      of certain chromosomes, probably due to identity-by-descent of those chromosomes
      in the parental genotypes. The variability in compounds associated with aroma was
      analyzed by a metabolomic approach based on GC-MS to profile 81 volatiles across
      the population from two locations. Quality-related traits were also studied to
      assess possible pleiotropic effects. Correlation-based analysis of the volatile
      dataset revealed that the peach volatilome is organized into modules formed by
      compounds from the same biosynthetic origin or which share similar chemical
      structures. QTL mapping showed clustering of volatile QTL included in the same
      volatile modules, indicating that some are subjected to joint genetic control.
      The monoterpene module is controlled by a unique locus at the top of LG4, a locus
      previously shown to affect the levels of two terpenoid compounds. At the bottom
      of LG4, a locus controlling several volatiles but also melting/non-melting and
      maturity-related traits was found, suggesting putative pleiotropic effects. In
      addition, two novel loci controlling lactones and esters in linkage groups 5 and
      6 were discovered. CONCLUSIONS: The results presented here give light on the mode
      of inheritance of the peach volatilome confirming previously loci controlling the
      aroma of peach but also identifying novel ones.

PMID- 24885291
TI  - Mito-nuclear interactions as drivers of gene movement on and off the X
      chromosome.
AB  - BACKGROUND: Mito-nuclear gene interactions regulate energy conversion, and are
      fundamental to eukaryotes. Generally, mito-nuclear coadaptation would be most
      efficient if the interacting nuclear genes were X-linked, because this maximizes
      the probability of favorable mito-nuclear allelic combinations co-transmitting
      across generations. Thus, under a coadaptation (CA) hypothesis, nuclear genes
      essential for mitochondrial function might be under selection to relocate to the
      X-chromosome. However, maternal inheritance predisposes the mitochondrial DNA
      (mtDNA) to accumulate variation that, while male-harming, is benign to females.
      Numerous nuclear genes were recently reported in Drosophila melanogaster, which
      exhibit male-specific patterns of differential expression when placed alongside
      different mtDNA haplotypes, suggesting that nuclear genes are sensitive to an
      underlying male-specific mitochondrial mutation load. These genes are thus
      candidates for involvement in mito-nuclear interactions driven by sexual conflict
      (SC), and selection might have moved them off the X-chromosome to facilitate an
      optimal evolutionary counter-response, through males, to the presence of male
      harming mtDNA mutations. Furthermore, the presence of male-harming mtDNA
      mutations could exert selection for modifiers on the Y-chromosome, thus placing
      these mito-sensitive nuclear genes at the center of an evolutionary tug-of-war
      between mitochondrion and Y-chromosome.We test these hypotheses by examining the
      chromosomal distributions of three distinct sets of mitochondrial-interacting
      nuclear genes in D. melanogaster; the first is a list of genes with mitochondrial
      annotations by Gene Ontologies, the second is a list comprising the core
      evolutionary-conserved mitochondrial proteome, and the third is a list of genes
      involved in male-specific responses to maternally-inherited mitochondrial
      variation and which might be putative targets of Y-chromosomal regulation.
      RESULTS: Genes with mitochondrial annotations and genes representing the
      mitochondrial proteome do not exhibit statistically-significant biases in
      chromosomal representation. However, genes exhibiting sex-specific sensitivity to
      mtDNA are under-represented on the X-chromosome, over-represented among genes
      known to be sensitive to Y-chromosomal variation, and among genes previously
      associated with male fitness, but under-represented among genes associated with
      direct sexual antagonism. CONCLUSIONS: Our results are consistent with the SC
      hypothesis, suggesting that mitochondrial mutational pressure selects for gene
      movement off-the-X, hence enabling mito-nuclear coadaptation to proceed along
      trajectories that result in optimized fitness in both sexes.

PMID- 24885293
TI  - Association of LRP5 genotypes with osteoporosis in Tunisian post-menopausal
      women.
AB  - BACKGROUND: Osteoporosis is a highly heritable trait. Among the genes associated
      with bone mineral density (BMD), the low-density lipoprotein receptor-related
      protein 5 gene (LRP5) has been consistently identified in Caucasians. However
      LRP5 contribution to osteoporosis in populations of other ethnicities remains
      poorly known. METHODS: To determine whether LRP5 polymorphisms Ala1330Val and
      Val667Met are associated with BMD in North Africans, these genotypes were
      analyzed in 566 post-menopausal Tunisian women with mean age of 59.5 +/- 7 .7
      years, of which 59.1% have low bone mass (T-score<-1 at spine or hip). RESULTS:
      In post-menopausal Tunisian women, 1330Val was weakly associated with reduced BMD
      T-score at lumbar spine (p=0.047) but not femur neck. Moreover, the TT/TC
      genotypes tended to be more frequent in women with osteopenia and osteoporosis
      than in women with normal BMD (p=0.066). Adjusting for body size and other
      potential confounders, LRP5 genotypes were no longer significantly associated
      with aBMD at any site. CONCLUSIONS: The less common Val667Met polymorphism showed
      no association with osteoporosis. The Ala1330Val polymorphism is weakly
      associated with lower lumbar spine bone density and osteopenia/osteoporosis in
      postmenopausal Tunisian women. These observations expand our knowledge about the
      contribution of LRP5 genetic variation to osteoporosis risk in populations of
      diverse ethnic origin.

PMID- 24885292
TI  - The expression of beclin-1, an autophagic gene, in hepatocellular carcinoma
      associated with clinical pathological and prognostic significance.
AB  - BACKGROUND: A role for autophagy, a conserved cellular response to stress, has
      recently been demonstrated in human cancers. Aberrant expression of Beclin-1, an
      important autophagic gene, has been reported in various human cancers. In the
      present study, we investigated the significance and relationship between Beclin-1
      expression and cell proliferation, apoptosis, microvessel density (MVD) and
      clinical pathological changes or prognosis in human hepatocellular carcinoma
      (HCC). METHODS: A total of 103 primary HCC patients were involved in the study.
      Expression of Beclin-1, PCNA, NET-1, Bcl-2, Bax, Survivin in cancer cells and
      CD34 in stromal microvessels were evaluated immunohistochemically in tissue
      microarrays comprising 103 cases of HCC and 57 matched adjacent nontumor liver
      tissues. Correlations between clinicopathological characteristics and survival of
      HCC patients were explored. RESULTS: The positive rate of Beclin-1 was
      significantly lower in HCC tissues than adjacent tissues (72.8 vs. 89.5%, chi2 =
      6.085, P = 0.015). In HCC, Beclin-1 expression was negatively correlated with
      cirrhosis background (r = -0.216, P = 0.029), Edmondson grade (r = -0.249, P =
      0.011), vascular invasion (r = -0.246, P = 0.012), PCNA (r = -0.242, P = 0.014),
      NET-1 (r = -0.245, P = 0.013), anti-apoptosis protein Bcl-2 (r = -0.245, P =
      0.013) and MVD (r = -0.292, P = 0.003), and positively correlated with pro
      apoptosis protein Bax (r = 0.242, P = 0.014).Significant differences in the 5
      year survival rates were seen among patients with Beclin-1 strong positive (++)
      (59.1%, 13/22), moderate positive (+) (28.3%, 15/53) and weak negative expression
      (-) (14.6%, 7/28) (P = 0.043). Significant differences were detected between
      Beclin-1 (++) and either Beclin-1 (+) (P = 0.036) or Beclin-1 (-) groups (P =
      0.008), but no significant difference between Beclin-1 (+) and Beclin-1 (-)
      groups (P = 0.281) was observed.Survival rates were positively related to high
      Beclin-1 co-expressed with low PCNA, NET-1, or Bcl-2, lower MVD, and high Bax.
      Univariate and multivariate Cox regression analysis revealed that Beclin-1
      expression was an independent indicator for overall survival in HCC patients (P <
      0.05). CONCLUSIONS: The pathogenesis and progression of HCC are associated with
      reduced autophagy. The expression of Beclin-1 and Bax in HCC tissues may provide
      a synergistic effect towards inhibiting HCC proliferation, infiltration,
      metastasis and angiogenesis. Beclin-1 expression may be a valuable prognostic
      marker of HCC.

PMID- 24885294
TI  - Genetic architecture of limit dextrinase inhibitor (LDI) activity in Tibetan wild
      barley.
AB  - BACKGROUND: Limit dextrinase inhibitor (LDI) inhibits starch degradation in
      barley grains during malting because it binds with limit dextrinase (LD). There
      is a wide genetic variation in LDI synthesis and inactivation during barley grain
      development and germination. However, the genetic control of LDI activity remains
      little understood. RESULTS: In this study, association analysis was performed on
      162 Tibetan wild accessions by using LDI activity, 835 Diversity Arrays
      Technology (DArT) markers and single nucleotide polymorphisms (SNPs) of the gene
      HvLDI encoding LDI. Two DArT markers, bpb-8347, bpb-0068, and 31 SNPs of HvLDI
      were significantly associated with LDI activity, explaining 10.0%, 6.6% and 13.4%
      of phenotypic variation, respectively. Bpb-8347 is located on chromosome 6H, near
      the locus of HvLDI, and bpb-0068 is located on 3H. CONCLUSIONS: The current
      results confirmed the locus of the gene controlling LDI activity and identified a
      new DArT markers associated with LDI activity. The SNPs associated with LDI
      activity may provide a new insight into the genetic variation of LDI activity in
      barley grains.

PMID- 24885295
TI  - A comparison of performance of plant miRNA target prediction tools and the
      characterization of features for genome-wide target prediction.
AB  - BACKGROUND: Deep-sequencing has enabled the identification of large numbers of
      miRNAs and siRNAs, making the high-throughput target identification a main
      limiting factor in defining their function. In plants, several tools have been
      developed to predict targets, majority of them being trained on Arabidopsis
      datasets. An extensive and systematic evaluation has not been made for their
      suitability for predicting targets in species other than Arabidopsis. Nor, these
      have not been evaluated for their suitability for high-throughput target
      prediction at genome level. RESULTS: We evaluated the performance of 11
      computational tools in identifying genome-wide targets in Arabidopsis and other
      plants with procedures that optimized score-cutoffs for estimating targets.
      Targetfinder was most efficient [89% 'precision' (accuracy of prediction), 97%
      'recall' (sensitivity)] in predicting 'true-positive' targets in Arabidopsis
      miRNA-mRNA interactions. In contrast, only 46% of true positive interactions from
      non-Arabidopsis species were detected, indicating low 'recall' values. Score
      optimizations increased the 'recall' to only 70% (corresponding 'precision': 65%)
      for datasets of true miRNA-mRNA interactions in species other than Arabidopsis.
      Combining the results of Targetfinder and psRNATarget delivers high true positive
      coverage, whereas the intersection of psRNATarget and Tapirhybrid outputs deliver
      highly 'precise' predictions. The large number of 'false negative' predictions
      delivered from non-Arabidopsis datasets by all the available tools indicate the
      diversity in miRNAs-mRNA interaction features between Arabidopsis and other
      species. A subset of miRNA-mRNA interactions differed significantly for features
      in seed regions as well as the total number of matches/mismatches. CONCLUSION:
      Although, many plant miRNA target prediction tools may be optimized to predict
      targets with high specificity in Arabidopsis, such optimized thresholds may not
      be suitable for many targets in non-Arabidopsis species. More importantly, non
      conventional features of miRNA-mRNA interaction may exist in plants indicating
      alternate mode of miRNA target recognition. Incorporation of these divergent
      features would enable next-generation of algorithms to better identify target
      interactions.

PMID- 24885296
TI  - From sequence to enzyme mechanism using multi-label machine learning.
AB  - BACKGROUND: In this work we predict enzyme function at the level of chemical
      mechanism, providing a finer granularity of annotation than traditional Enzyme
      Commission (EC) classes. Hence we can predict not only whether a putative enzyme
      in a newly sequenced organism has the potential to perform a certain reaction,
      but how the reaction is performed, using which cofactors and with susceptibility
      to which drugs or inhibitors, details with important consequences for drug and
      enzyme design. Work that predicts enzyme catalytic activity based on 3D protein
      structure features limits the prediction of mechanism to proteins already having
      either a solved structure or a close relative suitable for homology modelling.
      RESULTS: In this study, we evaluate whether sequence identity, InterPro or
      Catalytic Site Atlas sequence signatures provide enough information for bulk
      prediction of enzyme mechanism. By splitting MACiE (Mechanism, Annotation and
      Classification in Enzymes database) mechanism labels to a finer granularity,
      which includes the role of the protein chain in the overall enzyme complex, the
      method can predict at 96% accuracy (and 96% micro-averaged precision, 99.9% macro
      averaged recall) the MACiE mechanism definitions of 248 proteins available in the
      MACiE, EzCatDb (Database of Enzyme Catalytic Mechanisms) and SFLD (Structure
      Function Linkage Database) databases using an off-the-shelf K-Nearest Neighbours
      multi-label algorithm. CONCLUSION: We find that InterPro signatures are critical
      for accurate prediction of enzyme mechanism. We also find that incorporating
      Catalytic Site Atlas attributes does not seem to provide additional accuracy. The
      software code (ml2db), data and results are available online at
      http://sourceforge.net/projects/ml2db/ and as supplementary files.

PMID- 24885298
TI  - Complex consultations in primary care: a tool for assessing the range of health
      problems and issues addressed in general practice consultations.
AB  - BACKGROUND: There is an increasing recognition that many consultations in general
      practice involve several problems covering multiple disease domains. However
      there is a paucity of reliable tools and techniques to understand and quantify
      this phenomenon. The objective was to develop a tool that can be used to measure
      the number and type of problems discussed in primary care consultations. METHODS:
      Thirteen consultations between general practitioners and patients were initially
      videoed and reviewed to identify the problems and issues discussed. An iterative
      process involving a panel of clinicians and researchers and repeated cycles of
      testing and development was used to develop a measurement proforma and coding
      manual for assessment of video recorded consultations. The inter-rater
      reliability of this tool was assessed in 60 consultations. RESULTS: The problems
      requiring action were usually readily identified. However the different
      dimensions of the problem and how they were addressed required the identification
      and definition of 'issues'. A coding proforma was developed that allowed
      quantification of the numbers and types of health problems and issues discussed.
      Ten categories of issues were identified and defined. At the consultation level,
      inter-rater agreements for the number of problems discussed (within +/- 1), types
      of problems and issues were 98.3%, 96.5% and 90% respectively. The tool has
      subsequently been used to analyse 229 consultations. CONCLUSION: The iterative
      approach to development of the tool reflected the complexity of doctor-patient
      interactions. A reliable tool has been developed that can be used to analyse the
      number and range of problems managed in primary care consultations.

PMID- 24885297
TI  - Reexpression of LSAMP inhibits tumor growth in a preclinical osteosarcoma model.
AB  - BACKGROUND: Osteosarcomas are the most common primary malignant tumors of bone,
      showing complex chromosomal rearrangements with multiple gains and losses. A
      frequent deletion within the chromosomal region 3q13.31 has been identified by us
      and others, and is mainly reported to be present in osteosarcomas. The purpose of
      the study was to further characterize the frequency and the extent of the
      deletion in an extended panel of osteosarcoma samples, and the expression level
      of the affected genes within the region. We have identified LSAMP as the target
      gene for the deletion, and have studied the functional implications of LSAMP
      reexpression. METHODS: LSAMP copy number, expression level and protein level were
      investigated by quantitative PCR and western blotting in an osteosarcoma panel.
      The expression of LSAMP was restored in an osteosarcoma cell line, and
      differences in proliferation rate, tumor formation, gene expression, migration
      rate, differentiation capabilities, cell cycle distribution and apoptosis were
      investigated by metabolic dyes, tumor formation in vivo, gene expression
      profiling, time-lapse photography, differentiation techniques and flow cytometry,
      respectively. RESULTS: We found reduced copy number of LSAMP in 45/76
      osteosarcoma samples, reduced expression level in 25/42 samples and protein
      expression in 9/42 samples. By restoring the expression of LSAMP in a cell line
      with a homozygous deletion of the gene, the proliferation rate in vitro was
      significantly reduced and tumor growth in vivo was significantly delayed. In
      response to reexpression of LSAMP, mRNA expression profiling revealed consistent
      upregulation of the genes hairy and enhancer of split 1 (HES1), cancer/testis
      antigen 2 (CTAG2) and kruppel-like factor 10 (KLF10). CONCLUSIONS: The high
      frequency and the specificity of the deletion indicate that it is important for
      the development of osteosarcomas. The deletion targets the tumor suppressor
      LSAMP, and based on the functional evidence, the tumor suppressor function of
      LSAMP is most likely exerted by reducing the proliferation rate of the tumor
      cells, possibly by indirectly upregulating one or more of the genes HES1, CTAG2
      or KLF10. To our knowledge, this study describes novel functions of LSAMP, a
      first step to understanding the functional role of this specific deletion in
      osteosarcomas.

PMID- 24885299
TI  - A compact theory of magnetic nerve stimulation: predicting how to aim.
AB  - BACKGROUND: A compact theory that predicts quantitatively when and where magnetic
      neurostimulation will occur is needed as a guide to therapy, ideally providing a
      single equation that defines the target volume of tissue excited by single or
      dual coils. METHODS: A first-principles analysis of magnetic stimulation
      incorporating a simplified description of electromagnetic fields and a simplified
      cable theory of the axon yields a mathematical synthesis predicting how to aim.
      RESULTS: Nerve stimulation produced by a single circular coil having one or more
      closely packed turns occurs in donut shaped volume of tissue beneath the coil.
      Axons spanning several millimeters are the sites of magnetic stimulation. The
      sites of maximal transmembrane depolarization in nerve fibers correspond to
      points where the axons enter or exit this volume of magnetically induced voltage
      and current. The axonal membrane at one end is depolarized locally during the
      rising phase of current in the coil. The axonal membrane at the opposite end is
      depolarized locally during the falling phase of current in the coil. Penetration
      depths of several centimeters from the skin surface or approximately one to two
      coil radii are practical. With two coils placed in a figure-of-eight
      configuration the separate clockwise and counterclockwise currents generate
      magnetic fields that add, producing maximal stimulation of a spindle shaped
      volume, centered at a depth of one-third to one-half coil radius from the body
      surface. CONCLUSIONS: This condensed synthesis of electromagnetic theory and
      cable theories of axon physiology provides a partial solution to the targeting
      problem in peripheral and in transcranial magnetic stimulation.

PMID- 24885301
TI  - Development of an in vitro model to measure bioactivity of botulinum neurotoxin A
      in rat bladder muscle strips.
AB  - BACKGROUND: Botulinum toxin A (BoNT-A) is a new treatment modality in various
      causes of bladder dysfunction; like neurogenic detrusor overactivity and
      overactive bladder. The best technique of administrating BoNT-A in patients is
      unknown. A validated in vitro model could be used to investigate newer
      intravesical administration techniques of BoNT-A. In this study, we describe the
      development and validation of in vitro model to measure inhibitory effects of
      BoNT-A on bladder strip contractions. METHODS: Rat bladder strips were mounted in
      organ baths filled with Krebs' solution. The strips were stimulated chemically
      (80 mM potassium chloride, 1 MUM carbachol) and electrically (Electrical Field
      Stimulation (EFS) 100 shocks, 50 V, 20 Hz, every 3 minutes). The viability of the
      strips was measured by carbachol stimulation at the beginning and at the end of
      the experiments. The strips were incubated in various concentrations of BoNT-A
      (0.03, 0.2, 0.3 nM). Controls were incubated in Krebs' solution only. The
      inhibition of strip contraction induced by EFS was measured. These measurements
      were statistically analyzed with a log-logistic model representing diffusion.
      RESULTS: All strips remained viable during the experiments. Inhibition of strip
      contraction was observed after incubation with 0.3 nM BoNT-A. The measurements
      fitted to a log-logistic model describing diffusion of BoNT-A in the bladder
      strip. The parameters of the log-logistic model representing diffusion were
      significant for 0.3 nM BoNT-A. Incubation with 0.2 nM BoNT-A showed insignificant
      results for 2 out of 3 runs. Incubation with 0.03 nM BoNT-A did not result in
      significant inhibition of strip contractions. CONCLUSIONS: An in vitro model was
      developed and validated in which the inhibitory effect of low concentrations of
      BoNT-A on bladder strip contractions can be measured.

PMID- 24885303
TI  - Self-induced stereoselective in situ trifluoromethylation: preparation of
      spiro[indoline-3,3'-quinoline] via palladium-catalyzed cascade reaction.
AB  - An efficient method to prepare 1'H-spiro[indoline-3,3'-quinoline]-2',4'-diones
      and their trifluoromethylated products was developed via a palladium-catalyzed
      Sonogashira coupling/Wacker-type oxypalladation/cyclization cascade reaction. The
      amount of water in the reaction system played an important role in the in situ
      trifluoromethylation reaction, and the trifluoromethylation exhibited excellent
      molecular self-induced stereoselectivity. 

PMID- 24885300
TI  - A systematic review on improving cognition in schizophrenia: which is the more
      commonly used type of training, practice or strategy learning?
AB  - BACKGROUND: The purpose of this article was to conduct a review of the types of
      training offered to people with schizophrenia in order to help them develop
      strategies to cope with or compensate for neurocognitive or sociocognitive
      deficits. METHODS: We conducted a search of the literature using keywords such as
      "schizophrenia", "training", and "cognition" with the most popular databases of
      peer-reviewed journals. RESULTS: We reviewed 99 controlled studies in total
      (though nine did not have a control condition). We found that drill and practice
      training is used more often to retrain neurocognitive deficits while drill and
      strategy training is used more frequently in the context of sociocognitive
      remediation. CONCLUSIONS: Hypotheses are suggested to better understand those
      results and future research is recommended to compare drill and strategy with
      drill and practice training for both social and neurocognitive deficits in
      schizophrenia.

PMID- 24885302
TI  - Altering length and velocity feedback during a neuro-musculoskeletal simulation
      of normal gait contributes to hemiparetic gait characteristics.
AB  - BACKGROUND: Spasticity is an important complication after stroke, especially in
      the anti-gravity muscles, i.e. lower limb extensors. However the contribution of
      hyperexcitable muscle spindle reflex loops to gait impairments after stroke is
      often disputed. In this study a neuro-musculoskeletal model was developed to
      investigate the contribution of an increased length and velocity feedback and
      altered reflex modulation patterns to hemiparetic gait deficits. METHODS: A
      musculoskeletal model was extended with a muscle spindle model providing real
      time length and velocity feedback of gastrocnemius, soleus, vasti and rectus
      femoris during a forward dynamic simulation (neural control model). By using a
      healthy subject's base muscle excitations, in combination with increased feedback
      gains and altered reflex modulation patterns, the effect on kinematics was
      simulated. A foot-ground contact model was added to account for the interaction
      effect between the changed kinematics and the ground. The qualitative effect i.e.
      the directional effect and the specific gait phases where the effect is present,
      on the joint kinematics was then compared with hemiparetic gait deviations
      reported in the literature. RESULTS: Our results show that increased feedback in
      combination with altered reflex modulation patterns of soleus, vasti and rectus
      femoris muscle can contribute to excessive ankle plantarflexion/inadequate
      dorsiflexion, knee hyperextension/inadequate flexion and increased hip
      extension/inadequate flexion during dedicated gait cycle phases. Increased
      feedback of gastrocnemius can also contribute to excessive
      plantarflexion/inadequate dorsiflexion, however in combination with excessive
      knee and hip flexion. Increased length/velocity feedback can therefore contribute
      to two types of gait deviations, which are both in accordance with previously
      reported gait deviations in hemiparetic patients. Furthermore altered modulation
      patterns, in particular the reduced suppression of the muscle spindle feedback
      during swing, can contribute largely to an increased plantarflexion and knee
      extension during the swing phase and consequently to hampered toe clearance.
      CONCLUSIONS: Our results support the idea that hyperexcitability of length and
      velocity feedback pathways, especially in combination with altered reflex
      modulation patterns, can contribute to deviations in hemiparetic gait.
      Surprisingly, our results showed only subtle temporal differences between length
      and velocity feedback. Therefore, we cannot attribute the effects seen in
      kinematics to one specific type of feedback.

PMID- 24885304
TI  - Video observation of hand hygiene practices during routine companion animal
      appointments and the effect of a poster intervention on hand hygiene compliance.
AB  - BACKGROUND: Hand hygiene is considered one of the most important infection
      control measures in human healthcare settings, but there is little information
      available regarding hand hygiene frequency and technique used in veterinary
      clinics. The objectives of this study were to describe hand hygiene practices
      associated with routine appointments in companion animal clinics in Ontario, and
      the effectiveness of a poster campaign to improve hand hygiene compliance.
      RESULTS: Observation of hand hygiene practices was performed in 51 clinics for
      approximately 3 weeks each using 2 small wireless surveillance cameras: one in an
      exam room, and one in the most likely location for hand hygiene to be performed
      outside the exam room following an appointment. Data from 38 clinics were
      included in the final analysis, including 449 individuals, 1139 appointments
      before and after the poster intervention, and 10894 hand hygiene opportunities.
      Overall hand hygiene compliance was 14% (1473/10894), while before and after
      patient contact compliance was 3% (123/4377) and 26% (1145/4377), respectively.
      Soap and water was used for 87% (1182/1353) of observed hand hygiene attempts
      with a mean contact time of 4 s (median 2 s, range 1-49 s), while alcohol-based
      hand rub (ABHR) was used for 7% (98/1353) of attempts with a mean contact time of
      8 s (median 7 s, range 1-30 s). The presence of the posters had no significant
      effect on compliance, although some staff reported that they felt the posters did
      increase their personal awareness of the need to perform hand hygiene, and the
      posters had some effect on product contact times. CONCLUSIONS: Overall hand
      hygiene compliance in veterinary clinics in this study was low, and contact time
      with hand hygiene products was frequently below current recommendations. Use of
      ABHR was low despite its advantages over hand washing and availability in the
      majority of clinics. The poster campaign had a limited effect on its own, but
      could still be used as a component of a multimodal hand hygiene campaign.
      Improving the infection control culture in veterinary medicine would facilitate
      future campaigns and studies in this area, as well as overall patient and staff
      safety.

PMID- 24885305
TI  - Recombination locations and rates in beef cattle assessed from parent-offspring
      pairs.
AB  - BACKGROUND: Recombination events tend to occur in hotspots and vary in number
      among individuals. The presence of recombination influences the accuracy of
      haplotype phasing and the imputation of missing genotypes. Genes that influence
      genome-wide recombination rate have been discovered in mammals, yeast, and
      plants. Our aim was to investigate the influence of recombination on haplotype
      phasing, locate recombination hotspots, scan the genome for Quantitative Trait
      Loci (QTL) and identify candidate genes that influence recombination, and
      quantify the impact of recombination on the accuracy of genotype imputation in
      beef cattle. METHODS: 2775 Angus and 1485 Limousin parent-verified sire/offspring
      pairs were genotyped with the Illumina BovineSNP50 chip. Haplotype phasing was
      performed with DAGPHASE and BEAGLE using UMD3.1 assembly SNP (single nucleotide
      polymorphism) coordinates. Recombination events were detected by comparing the
      two reconstructed chromosomal haplotypes inherited by each offspring with those
      of their sires. Expected crossover probabilities were estimated assuming no
      interference and a binomial distribution for the frequency of crossovers. The
      BayesB approach for genome-wide association analysis implemented in the GenSel
      software was used to identify genomic regions harboring QTL with large effects on
      recombination. BEAGLE was used to impute Angus genotypes from a 7K subset to the
      50K chip. RESULTS: DAGPHASE was superior to BEAGLE in haplotype phasing, which
      indicates that linkage information from relatives can improve its accuracy. The
      estimated genetic length of the 29 bovine autosomes was 3097 cM, with a genome
      wide recombination distance averaging 1.23 cM/Mb. 427 and 348 windows containing
      recombination hotspots were detected in Angus and Limousin, respectively, of
      which 166 were in common. Several significant SNPs and candidate genes, which
      influence genome-wide recombination were localized in QTL regions detected in the
      two breeds. High-recombination rates hinder the accuracy of haplotype phasing and
      genotype imputation. CONCLUSIONS: Small population sizes, inadequate half-sib
      family sizes, recombination, gene conversion, genotyping errors, and map errors
      reduce the accuracy of haplotype phasing and genotype imputation. Candidate
      regions associated with recombination were identified in both breeds.
      Recombination analysis may improve the accuracy of haplotype phasing and genotype
      imputation from low- to high-density SNP panels.

PMID- 24885306
TI  - High co-occurrence of anorectal chlamydia with urogenital chlamydia in women
      visiting an STI clinic revealed by routine universal testing in an observational
      study; a recommendation towards a better anorectal chlamydia control in women.
AB  - BACKGROUND: Symptom- and sexual history-based testing i.e., testing on
      indication, for anorectal sexually transmitted infections (STIs) in women is
      common. Yet, it is unknown whether this strategy is effective. Moreover, little
      is known about alternative transmission routes i.e. by fingers/toys. This study
      assesses anorectal STI prevalence and infections missed by current testing
      practice, thereby informing the optimal control strategy for anorectal STIs in
      women. METHODS: Women (n = 663) attending our STI-clinic between May 2012-July
      2013 were offered routine testing for anorectal and urogenital Chlamydia
      trachomatis and Neisseria gonorrhoeae. Data were collected on demographics,
      sexual behaviour and symptoms. Women were assigned to one of the categories:
      indication (reported anal sex/symptoms), fingers/toys (only reported use of
      fingers/toys), or without indication. RESULTS: Of women, 92% (n = 654)
      participated. There were 203 reports (31.0%) of anal sex and/or symptoms
      (indication), 48 reports (7.3%) of only using fingers/toys (fingers/toys), and
      403 reports (61.6%) of no anal symptoms, no anal sex and no anal use of
      fingers/toys (without indication). The overall prevalence was 11.2% (73/654) for
      urogenital chlamydia and 8.4% (55/654) for anorectal chlamydia. Gonorrhoea
      infections were not observed. Prevalence of anorectal chlamydia was 7.9% (16/203)
      for women with indication and 8.6% (39/451) for all other women (P = 0.74). Two
      thirds (39/55) of anorectal infections were diagnosed in women without
      indication. Isolated anorectal chlamydia was rare (n = 3): of all women with an
      anorectal infection, 94.5% (52/55) also had co-occurrence of urogenital
      chlamydia. Of all women with urogenital chlamydia, 71.2% (52/73) also had
      anorectal chlamydia. CONCLUSIONS: Current selective testing on indication of
      symptoms and sexual history is not an appropriate control strategy for anorectal
      chlamydia in women visiting an STI clinic. Routine universal anorectal testing is
      feasible and may be a possible control strategy in women. Yet costs may be a
      problem. When more restricted control measures are preferred, possible
      alternatives include (1) anorectal testing only in women with urogenital
      chlamydia (problem: treatment delay or loss to follow up), and (2) direct
      treatment for urogenital chlamydia that is effective for anorectal chlamydia as
      well.

PMID- 24885307
TI  - Influence of electroencephalography neurofeedback training on episodic memory: a
      randomized, sham-controlled, double-blind study.
AB  - The relationships between memory processes and oscillatory electroencephalography
      (EEG) are well established. Neurofeedback training (NFT) may cause participants
      to better regulate their brain EEG oscillations. The present study is a double
      blind sham-controlled design investigating the effect of NFT on memory. NFT
      included up-training upper alpha (UA) band, up-training sensory-motor rhythm
      (SMR) band and sham protocol. Thirty healthy adult volunteers were randomly
      divided into three treatment groups. NFT sessions (30 min each) took place twice
      weekly for a total of 10 sessions while memory testing took place pre- and post
      training. The results indicate dissociation between SMR and UA NFT and different
      memory processes. While the SMR protocol resulted in improving automatic, item
      specific and familiarity-based processes in memory, the UA protocol resulted in
      improved strategic and controlled recollection. The implications of the results
      are discussed. 

PMID- 24885309
TI  - CETA and pharmaceuticals: impact of the trade agreement between Europe and Canada
      on the costs of prescription drugs.
AB  - On a per capita basis, Canadian drug costs are already the second highest in the
      world after the United States and are among the fastest rising in the
      Organization for Economic Co-Operation and Development. The Comprehensive
      Economic and Trade Agreement (CETA) between the European Union (EU) and Canada
      will further exacerbate the rise in costs by:  Committing Canada to creating a
      new system of patent term restoration thereby delaying entry of generic medicines
      by up to two years; Locking in Canada's current term of data protection, and
      creating barriers for future governments wanting to reverse it;  Implementing a
      new right of appeal under the patent linkage system that will create further
      delays for the entry of generics.CETA will only affect intellectual property
      rights in Canada-not the EU. This analysis estimates that CETA's provisions will
      increase Canadian drug costs by between 6.2% and 12.9% starting in 2023. The
      Canadian government committed to compensating provinces for the rise in costs for
      their public drug plans. Importantly, this means that people paying out-of-pocket
      for their drugs or receiving them through private insurance, will be charged
      twice: once through higher drug costs and once more through their federal
      taxes.As drug costs continue to grow, there are limited options available for
      provincial/territorial governments: restrict the choice of medicines in public
      drug plans; transfer costs to patients who typically are either elderly or sick;
      or take money from other places in the health system, and threaten the viability
      of Canada's single payer system. CETA will therefore negatively impact the
      ability of Canada to offer quality health care.

PMID- 24885308
TI  - Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell
      proliferation, migration and invasion in epithelial ovarian cancer.
AB  - BACKGROUND: The Forkhead box M1 (FOXM1), an important regulator of cell
      differentiation and proliferation, is overexpressed in a number of aggressive
      human carcinomas. The purpose of this study was to examine the expression levels
      of FOXM1 in epithelial ovarian cancer (EOC), to identify the relationship between
      FOXM1 expression and patient survival, and to investigate the role of FOXM1 in
      human ovarian cancer development. METHODS: Immunohistochemical analysis for FOXM1
      was performed in a total of 158 ovarian tissue specimens, all with linked
      clinical outcome data. Kaplan-Meier method and Cox proportional hazards analysis
      were used to relate FOXM1 expression to clinicopathological variables and to
      progression-free survival (PFS) and overall survival (OS). In vitro studies were
      performed to determine the function of FOXM1 in cell proliferation, migration and
      invasion in EOC cells using pcDNA3.1-FOXM1 and FOXM1 shRNA. RESULTS: Elevated
      FOXM1 levels were associated with lymph node metastasis (P = 0.009), but not with
      age, FIGO stage, histological grade and histological type. Patients with high
      expression of FOXM1 had poorer PFS (P = 0.0001) and OS (P < 0.0001) than patients
      with low expression of FOXM1. Furthermore, multivariate analyses indicated that
      FOXM1 positivity was an independent prognostic factor for PFS (P = 0.046) and OS
      (P = 0.022), respectively. Overexpression of FOXM1 increased expression and
      activity of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial
      growth factor-A (VEGF-A), and cancer cell proliferation, migration and invasion
      of HO-8910 cells, whereas knockdown of FOXM1 reduced expression and activity of
      MMP-2, MMP-9 and VEGF-A, and cancer cell proliferation, migration and invasion of
      HO-8910 PM cells. CONCLUSIONS: Our results suggest that FOXM1 expression is
      likely to play important roles in EOC development and progression. FOXM1
      expression is a potential prognostic factor for PFS and OS, and it could be a
      novel treatment target in EOC patients.

PMID- 24885310
TI  - Solitary glandular papilloma of the peripheral lung: a report of two cases.
AB  - Solitary papilloma of the lung is thought to be a rare benign epithelial tumor,
      and complete surgical resection is currently the standard treatment for this
      pathology. However, some cases of papilloma have reportedly shown malignant
      potential. We report two cases of solitary glandular papilloma of the peripheral
      lung that were treated by thoracoscopic partial resection. The first patient
      presented with a nodular lesion in the lower lobe of the left lung that was
      detected on a follow-up chest computed tomography (CT) scan after treatment for
      laryngeal cancer. Partial lung resection was performed by video-assisted
      thoracoscopic surgery. In the second patient, a nodular lesion was incidentally
      identified in the lower lobe of the left lung during a health check-up. Partial
      lung resection was again performed by video-assisted thoracoscopic surgery. The
      postoperative course in both cases was uneventful, and no recurrences have been
      observed as of 44 months and 41 months postoperatively, respectively. To the best
      of our knowledge, malignant transformation has been reported both with the
      squamous type and the mixed type of solitary papilloma of the lung. The glandular
      variant has shown no tendency toward local recurrence after local excision and
      has no apparent malignant potential. Local excision is thus recommended for
      solitary glandular papilloma in order to preserve pulmonary function. 

PMID- 24885311
TI  - The contribution of reduction in malaria as a cause of rapid decline of under
      five mortality: evidence from the Rufiji Health and Demographic Surveillance
      System (HDSS) in rural Tanzania.
AB  - BACKGROUND: Under-five mortality has been declining rapidly in a number of sub
      Saharan African settings. Malaria-related mortality is known to be a major
      component of childhood causes of death and malaria remains a major focus of
      health interventions. The paper explored the contribution of malaria relative to
      other specific causes of under-five deaths to these trends. METHODS: This paper
      uses longitudinal demographic surveillance data to examine trends and causes of
      death of under-five mortality in Rufiji, whose population has been followed for
      over nine years (1999-2007). Causes of death, determined by the verbal autopsy
      technique, are analysed with Arriaga's decomposition method to assess the
      contribution of declining malaria-related mortality relative to other causes of
      death as explaining a rapid decline in overall childhood mortality. RESULTS: Over
      the 1999-2007 period, under-five mortality rate in Rufiji declined by 54.3%, from
      33.3 to 15.2 per 1,000 person-years. If this trend is sustained, Rufiji will be a
      locality that achieves MDG4 target. Although hypotrophy at birth remained the
      leading cause of death for neonates, malaria remains as the leading cause of
      death for post-neonates followed by pneumonia. However, declines in malaria death
      rates accounted for 49.9% of the observed under-five mortality decline while all
      perinatal causes accounted for only 19.9%. CONCLUSION: To achieve MDG 4 in
      malaria endemic settings, health programmes should continue efforts to reduce
      malaria mortality and more efforts are also needed to improve newborn survival.

PMID- 24885312
TI  - In silico analyses reveal common cellular pathways affected by loss of
      heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin's lymphoma
      (NHL).
AB  - BACKGROUND: The analysis of cellular networks and pathways involved in
      oncogenesis has increased our knowledge about the pathogenic mechanisms that
      underlie tumour biology and has unmasked new molecular targets that may lead to
      the design of better anti-cancer therapies. Recently, using a high resolution
      loss of heterozygosity (LOH) analysis, we identified a number of potential tumour
      suppressor genes (TSGs) within common LOH regions across cases suffering from two
      of the most common forms of Non-Hodgkin's lymphoma (NHL), Follicular Lymphoma
      (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the
      protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a
      common event in the lymphomagenesis of these B-cell lymphomas. The present study
      aimed to determine the cellular pathways affected by the inactivation of these
      TSGs including PTPRJ in FL and DLBCL tumourigenesis. RESULTS: Pathway analytical
      approaches identified that candidate TSGs located within common LOH regions
      participate within cellular pathways, which may play a crucial role in FL and
      DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified
      genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated
      in NHL may play an important role in tumourigenesis. We also detected genes that
      are differentially expressed in cases with and without LOH of PTPRJ, such as
      NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent
      3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was
      also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events
      causing inactivation of PTPRJ, apart from possibly inducing a constitutive
      activation of these pathways by reduction or abrogation of its dephosphorylation
      activity, may also induce upregulation of these pathways when inactivated. This
      finding implicates these pathways in the lymphomagenesis and progression of FL
      and DLBCL. CONCLUSIONS: The evidence obtained in this research supports findings
      suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it
      indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell
      tumours and suggests that activation of PTPRJ might be an interesting novel
      chemotherapeutic target for the treatment of these B-cell tumours.

PMID- 24885314
TI  - The epidemiology of childhood tuberculosis in the Netherlands: still room for
      prevention.
AB  - BACKGROUND: The occurrence of tuberculosis (TB) among children has long been
      neglected as a public health concern. However, any child with TB is a sentinel
      event indicating recent transmission. Vaccination, early case finding and
      treatment of those latently infected with TB can prevent cases, severe morbidity
      and unnecessary death. METHOD: The objective of the study was to describe the
      occurrence of TB events among children in the Netherlands which may be avoided
      through preventive measures. For this purpose we performed a trend analysis of
      routine Dutch TB and LTBI (surveillance data in 1993-2012 and a descriptive
      analysis of children with TB and with LTBI diagnosed in 2005-2012). RESULTS:
      Overall childhood TB incidence has declined over the last two decades from 3.6 in
      1993 to 1.9 per 100,000 children in 2012. The decline was stronger among Dutch
      born children compared to foreign-born children. In 2005-2012 64% of childhood TB
      cases were detected through active case finding. Foreign-born children with TB
      were less likely to be detected through active case finding, when not detected
      through post-entry TB screening. Childhood TB diagnosis was culture confirmed in
      68% of passively detected cases and 12% of actively detected cases. Of 1,049
      children with LTBI started on preventive treatment in 2005-2012, 90% completed
      treatment. In 37% of all childhood TB cases there was at least one 'missed
      opportunity' for prevention. Thirty nine percent of child TB patients eligible
      for BCG were not vaccinated. CONCLUSION: Children with TB in the Netherlands are
      generally detected at an early stage and treatment completion rates are high.
      However, more TB cases among children can be prevented through enhancing TB case
      finding and screening and preventive treatment of latent TB infection among
      migrant children, and improving the coverage of BCG vaccination among eligible
      risk groups.

PMID- 24885313
TI  - A novel genetic map of wheat: utility for mapping QTL for yield under different
      nitrogen treatments.
AB  - BACKGROUND: Common wheat (Triticum aestivum L.) is one of the most important food
      crops worldwide. Wheat varieties that maintain yield (YD) under moderate or even
      intense nitrogen (N) deficiency can adapt to low input management systems. A
      detailed genetic map is necessary for both wheat molecular breeding and genomics
      research. In this study, an F6:7 recombinant inbred line population comprising
      188 lines was used to construct a novel genetic map and subsequently to detect
      quantitative trait loci (QTL) for YD and response to N stress. RESULTS: A genetic
      map consisting of 591 loci distributed across 21 wheat chromosomes was
      constructed. The map spanned 3930.7 cM, with one marker per 6.7 cM on average.
      Genomic simple sequence repeat (g-SSR), expressed sequence tag-derived
      microsatellite (e-SSR), diversity arrays technology (DArT), sequence-tagged sites
      (STS), sequence-related amplified polymorphism (SRAP), and inter-simple sequence
      repeat (ISSR) molecular markers were included in the map. The linear
      relationships between loci found in the present map and in previously compiled
      physical maps were presented, which were generally in accordance. Information on
      the genetic and physical positions and allele sizes (when possible) of 17 DArT,
      50 e-SSR, 44 SRAP, five ISSR, and two morphological markers is reported here for
      the first time. Seven segregation distortion regions (SDR) were identified on
      chromosomes 1B, 3BL, 4AL, 6AS, 6AL, 6BL, and 7B. A total of 22 and 12 QTLs for YD
      and yield difference between the value (YDDV) under HN and the value under LN
      were identified, respectively. Of these, QYd-4B-2 and QYddv-4B, two major stable
      QTL, shared support interval with alleles from KN9204 increasing YD in LN and
      decreasing YDDV. We probe into the use of these QTLs in wheat breeding programs.
      Moreover, factors affecting the SDR and total map length are discussed in depth.
      CONCLUSIONS: This novel map may facilitate the use of novel markers in wheat
      molecular breeding programs and genomics research. Moreover, QTLs for YD and YDDV
      provide useful markers for wheat molecular breeding programs designed to increase
      yield potential under N stress.

PMID- 24885315
TI  - Non-adherence to self-care practices & medication and health related quality of
      life among patients with type 2 diabetes: a cross-sectional study.
AB  - BACKGROUND: Non-adherence to lifestyle modification among diabetic patients
      develops the short-term risks and the long-term complications as well as declines
      the quality of life. This study aimed to find out the association between non
      adherence to self-care practices, medication and health related quality of life
      (HR-QoL) among type 2 diabetic patients. METHODS: At least 1 year diagnosed
      patients with type 2 diabetes (N = 500), age>25 years were conveniently selected
      from the Out-Patient Department of Bangladesh Institute of Health Sciences
      Hospital. Patients' self-care practices were assessed via interviewer
      administered questionnaires using an analytical cross-sectional design. HRQoL was
      assessed by an adapted and validated Bangla version of the EQ-5D (EuroQol Group,
      2009) questionnaire which has five domains- mobility, self-care, usual
      activities, pain/discomfort and anxiety/depression and two levels on each
      dimension. EQ-5D responses were further translated into single summery EQ-5D
      index using UK TTO value set. Patients' were considered as non-adhered to self
      care practices according to the guidelines of Diabetic Association of Bangladesh.
      Multivariable linear regression was used to assess the association between non
      adherence towards self-care practices and HRQoL. RESULTS: Among the study
      patients, 50.2% were females and mean +/- SD age was 54.2 (+/-11.2) years. Non
      adherence rate were assessed for: blood glucose monitoring (37%), diet (44.8%),
      foot care (43.2%), exercise (33.2%) and smoking (37.2%). About 50.4% patients had
      problem in mobility, 28.2% in self-care, 47.6% in usual activities, 72.8% in
      pain/discomfort and 73.6% in anxiety/depression. On chi-squared test, significant
      association was found between non adherence to foot care and problem with
      mobility, self-care and usual activities (p < 0.05). Significant association was
      also found between non-adherence to exercise and poor mobility, self- care, usual
      activities, pain and anxiety (p < 0.05). Non-adherence to diet was associated
      with poor mobility (p < 0.05). In multivariable linear regression non-adherence
      to foot care (p = 0.0001), exercise (p = 0.0001), and smoking (p = 0.047) showed
      significant association with EQ-5D index after adjusting co-variates.
      CONCLUSIONS: In this study, patients who have a non-adherence rate also have a
      lower quality of life.

PMID- 24885317
TI  - Effects of a TELephone Counselling Intervention by Pharmacist (TelCIP) on
      medication adherence, patient beliefs and satisfaction with information for
      patients starting treatment: study protocol for a cluster randomized controlled
      trial.
AB  - BACKGROUND: Adherence to medication is often low. Pharmacists may improve
      adherence, but a one-size-fits-all approach will not work: different patients
      have different needs. Goal of the current study is to assess the effectiveness of
      a patient-tailored, telephone-based intervention by a pharmacist at the start of
      pharmacotherapy aimed at improving medication adherence, satisfaction with
      information and counselling and the beliefs about medicines. METHODS/DESIGN: A
      cluster randomized controlled intervention trial in 30 Dutch pharmacies, randomly
      assigned to 1 of 2 intervention groups. Each group consists of an intervention
      arm and an usual care arm. The intervention arm in the first group is the usual
      care arm in the second group and vice versa. One intervention arm focuses on
      patients starting with antidepressants or bisphosphonates and the other on
      antilipaemic drugs or renin angiotensin system (RAS)-inhibitors. The intervention
      consists of a telephone call by a pharmacist 2 or 3 weeks after a new
      prescription. A random sample of pharmacies will send questionnaires 3 months
      after the first prescription. This contains socio-demographic questions, a
      measure of beliefs about medicines (BMQ), satisfaction with information received
      (SIMS, abbreviated) and frequency of pharmacy counselling (Consumer Quality
      Index, CQI, abbreviated). The primary outcome measure will be medication
      adherence calculated from dispensing records retrieved 12 months after the
      intervention. Patients' beliefs on medication, perception of the quality of
      information received and pharmacy counselling are secondary outcomes. DISCUSSION:
      The TelCIP study will determine the effectiveness of telephone counselling to
      improve adherence in patients initiating a new treatment. By measuring
      satisfaction with information and counselling and beliefs about medication the
      study will also give clues for the reason of a potential increase in adherence.
      Finally the study will provide information on which patients are most likely to
      benefit from this intervention. TRIAL REGISTRATION: The trial is registered at
      http://www.trialregister.nl under the identifier NTR3237.

PMID- 24885316
TI  - Are public health professionals prepared for public health genomics? A cross
      sectional survey in Italy.
AB  - BACKGROUND: Public health genomics is an emerging multidisciplinary approach,
      which aims to integrate genome-based knowledge in a responsible and effective way
      into public health. Despite several surveys performed to evaluate knowledge,
      attitudes and professional behaviors of physicians towards predictive genetic
      testing, similar surveys have not been carried out for public health
      practitioners. This study is the first to assess knowledge, attitudes and
      training needs of public health professionals in the field of predictive genetic
      testing for chronic diseases. METHODS: A self-administered questionnaire was used
      to carry out a cross-sectional survey of a random sample of Italian public health
      professionals. RESULTS: A response rate of 67.4% (797 questionnaires) was
      achieved. Italian public health professionals have the necessary attitudinal
      background to contribute to the proper use of predictive genetic testing for
      chronic diseases, but they need additional training to increase their
      methodological knowledge. Knowledge significantly increases with exposure to
      predictive genetic testing during postgraduate training (odds ratio (OR) = 1.74,
      95% confidence interval (CI) = 1.05-2.88), time dedicated to continuing medical
      education (OR = 1.53, 95% CI = 1.14-2.04) and level of English language knowledge
      (OR = 1.36, 95% CI = 1.07-1.72). Adequate knowledge is the strongest predictor of
      positive attitudes from a public health perspective (OR = 3.98, 95% CI = 2.44
      6.50). Physicians show a lower level of knowledge and more public health
      attitudes than other public health professionals do. About 80% of public health
      professionals considered their knowledge inadequate and 86.0% believed that it
      should be improved through specific postgraduate training courses. CONCLUSIONS:
      Specific and targeted training initiatives are needed to develop a skilled public
      health workforce competent in identifying genomic technology that is ready for
      use in population health and in modeling public health genomic programs and
      primary care services that need to be developed, implemented and evaluated.

PMID- 24885318
TI  - Fertility intentions among HIV positive women aged 18-49 years in Addis Ababa
      Ethiopia: a cross sectional study.
AB  - BACKGROUND: Given the degree of HIV epidemic among women and the current
      antiretroviral therapy (ART) scale up in Ethiopia; considering the issue of
      fertility is vital to ensure the delivery of integrated reproductive health along
      with prevention services provided to positive women. This study was aimed to
      assess fertility intentions of women living with HIV attending public health
      institutions (hospitals & health centers) in Addis Ababa, Ethiopia. METHODS:
      Institution based cross sectional survey was conducted, among 1855 HIV positive,
      women aged 18-49 years selected from different public health facilities in Addis
      Ababa; from June to October 2012. Information was gathered by using interviewer
      administered questionnaires. Data were double entered in EPI Info version 3.5.2
      software, cleaned finally exported to IBM SPSS statistics version 20 for
      analysis. Logistic regression models were used to predict the association of
      study variables and adjusted for possible confounders. RESULT: Overall, 44% of
      women reported fertility intention. ART users had higher fertility intention
      (AOR; 1.26, 95%CI; 1.01 to 1.60) than ART naive. In addition to this, having
      partner being on sexual relationship, young age, being single and having fewer or
      no children were found to be predictors of fertility intentions. The presence of
      ART, improvement of health condition and the influence of husband were the main
      reasons for childbearing intentions of women in the study area. CONCLUSION: A
      considerable proportion of women reported fertility intention. There was an
      association between fertility intentions and ART use. It is important for health
      care providers and policy makers to strengthen the fertility need of HIV positive
      women along with HIV care so that women may decide freely and responsibly on
      their fertility issues.

PMID- 24885319
TI  - Diagnostic value of serum HE4 in endometrial cancer: a meta-analysis.
AB  - BACKGROUND: Endometrial cancer (EC) is a common female malignant cancer. The age
      of incidence has become younger than before. If the diagnosis is during stage I,
      then the survival rate is about 90%. To date, there are no specific tumor markers
      for endometrial cancer. We usually use serum CA125 to help in diagnosing it.
      However, a serum biomarker CA125 greater than 35 U/ml is not useful in diagnosing
      EC at an early stage. Now, human epididymis protein 4 (HE4) has been intensively
      studied, and has been described as a new marker for ovarian cancer. The goal of
      this study was to evaluate the clinical value of serum HE4 in the diagnosis of
      endometrial cancer by meta-analysis. METHODS: We used MEDLINE, EMBASE, Cochrane
      Library and CBM databases to search the literature. The meta-analysis was
      performed by using Meta-Disc 1.4 software. RESULTS: All data we obtained showed
      that the major advantage of HE4 lies in its specificity in endometrial cancer
      diagnosis. Its sensitivity in serum was not as high as expected. But this
      evidence is not enough. CONCLUSIONS: Additional studies, particularly to evaluate
      HE4's capability in identifying EC at an early stage, will be needed.

PMID- 24885320
TI  - Antibody-dependent infection of human macrophages by severe acute respiratory
      syndrome coronavirus.
AB  - BACKGROUND: Public health risks associated to infection by human coronaviruses
      remain considerable and vaccination is a key option for preventing the resurgence
      of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously
      reported that antibodies elicited by a SARS-CoV vaccine candidate based on
      recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of
      immune cell lines. These observations prompted us to investigate the molecular
      mechanisms and responses to antibody-mediated infection in human macrophages.
      METHODS: We have used primary human immune cells to evaluate their susceptibility
      to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence
      microscopy and real-time quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) were utilized to assess occurrence and consequences of
      infection. To gain insight into the underlying molecular mechanism, we performed
      mutational analysis with a series of truncated and chimeric constructs of
      fragment crystallizable gamma receptors (FcgammaR), which bind antibody-coated
      pathogens. RESULTS: We show here that anti-Spike immune serum increased infection
      of human monocyte-derived macrophages by replication-competent SARS-CoV as well
      as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with
      SARS-CoV, however, did not support productive replication of the virus. Purified
      anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse
      immune serum, were sufficient to enhance infection. Antibody-mediated infection
      was dependent on signaling-competent members of the human FcgammaRII family,
      which were shown to confer susceptibility to otherwise naive ST486 cells, as
      binding of immune complexes to cell surface FcgammaRII was necessary but not
      sufficient to trigger antibody-dependent enhancement (ADE) of infection.
      Furthermore, only FcgammaRII with intact cytoplasmic signaling domains were
      competent to sustain ADE of SARS-CoVpp infection, thus providing additional
      information on the role of downstream signaling by FcgammaRII. CONCLUSIONS: These
      results demonstrate that human macrophages can be infected by SARS-CoV as a
      result of IgG-mediated ADE and indicate that this infection route requires
      signaling pathways activated downstream of binding to FcgammaRII receptors.

PMID- 24885321
TI  - Laboratory assessment of sensitive molecular tools for detection of low levels of
      Echinococcus multilocularis-eggs in fox (Vulpes vulpes) faeces.
AB  - BACKGROUND: In endemic areas with very low infection prevalence, the frequency
      and intensity of Echinococcus multilocularis can be extremely low. This
      necessitates efficient, specific and sensitive molecular tools. We wanted to
      compare the existing molecular tools, used in the Norwegian national surveillance
      programme, and compare these with new techniques for detection of this zoonotic
      pathogen in fox faeces. Here we present the results of screening samples
      containing a known level of E. multilocularis eggs with two highly sensitive DNA
      isolation and extraction methods combined with one conventional PCR and three
      real-time PCR methods for detection. METHODS: We performed a comparison of two
      extraction protocols; one based on sieving of faecal material and one using
      targeted DNA sampling. Four methods of molecular detection were tested on E.
      multilocularis-egg spiked fox faeces. RESULTS: There were significant differences
      between the multiplex PCR/egg sieving DNA extraction methods compared to the new
      DNA fishing method and the three real-time PCR assays. Results also indicate that
      replicates of the PCR-reactions improve detection sensitivity when egg numbers
      are low. CONCLUSIONS: The results indicate that the use of real-time PCR combined
      with targeted DNA extraction, improves the sensitivity of E. multilocularis
      detection in faecal samples containing low numbers of E. multilocularis eggs.
      Results also indicate the importance of replicates of the PCR-reactions when
      pathogen levels are low.

PMID- 24885322
TI  - A qualitative exploration of attitudes towards alcohol, and the role of parents
      and peers of two alcohol-attitude-based segments of the adolescent population.
AB  - BACKGROUND: An earlier study using social marketing and audience segmentation
      distinguished five segments of Dutch adolescents aged 12-18 years based on their
      attitudes towards alcohol. The present, qualitative study focuses on two of these
      five segments ('ordinaries' and 'ordinary sobers') and explores the attitudes of
      these two segments towards alcohol, and the role of parents and peers in their
      alcohol use in more detail. METHODS: This qualitative study was conducted in the
      province of North-Brabant, the Netherlands. With a 28-item questionnaire,
      segments of adolescents were identified. From the ordinaries and ordinary sobers
      who were willing to participate in a focus group, 55 adolescents (30 ordinaries
      and 25 ordinary sobers) were selected and invited to participate. Finally, six
      focus groups were conducted with 12-17 year olds, i.e., three interviews with 17
      ordinaries and three interviews with 20 ordinary sobers at three different high
      schools. RESULTS: The ordinaries thought that drinking alcohol was fun and
      relaxing. Curiosity was an important factor in starting to drink alcohol. Peer
      pressure played a role, e.g., it was difficult not to drink when peers were
      drinking. Most parents advised their child to drink a small amount only. The
      attitude of ordinary sobers towards alcohol was that drinking alcohol was stupid;
      moreover, they did not feel the need to drink. Most parents set strict rules and
      prohibited the use of alcohol before the age of 16. CONCLUSIONS: Qualitative
      insight into the attitudes towards alcohol and the role played by parents and
      peers, revealed differences between ordinaries and ordinary sobers. Based on
      these differences and on health education theories, starting points for the
      development of interventions, for both parents and adolescents, are formulated.
      Important starting points for interventions targeting ordinaries are reducing
      perceived peer pressure and learning to make one's own choices. For the ordinary
      sobers, an important starting point includes enabling them to express to others
      that they do not feel the need to drink alcohol. Starting points for parents
      include setting strict rules, restricting alcohol availability at home and
      monitoring their child's alcohol use.

PMID- 24885323
TI  - Frailty index of deficit accumulation and falls: data from the Global
      Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort.
AB  - BACKGROUND: To investigate the association between frailty index (FI) of deficit
      accumulation and risk of falls, fractures, death and overnight hospitalizations
      in women aged 55 years and older. METHODS: The data were from the Global
      Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort. In this 3
      year longitudinal, observational cohort study, women (N=3,985) aged >= 55 years
      were enrolled between May 2008 and March 2009 in Hamilton, Canada. A FI including
      co-morbidities, activities of daily living, symptoms and signs, and healthcare
      utilization was constructed using 34 health deficits at baseline. Relationship
      between the FI and falls, fractures, death and overnight hospitalizations was
      examined. RESULTS: The FI was significantly associated with age, with a mean rate
      of deficit accumulation across baseline age of 0.004 or 0.021 (on a log scale)
      per year. During the third year of follow-up, 1,068 (31.89%) women reported at
      least one fall. Each increment of 0.01 on the FI was associated with a
      significantly increased risk of falls during the third year of follow-up (odds
      ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02-1.03). The area under the
      curve (AUC) of the predictive model was 0.69 (95% CI: 0.67-0.71). Results of
      subgroup and sensitivity analyses indicated the relationship between the FI and
      risk of falls was robust, while bootstrap analysis judged its internal
      validation. The FI was significantly related to fractures (hazard ratio [HR]:
      1.02, 95% CI: 1.01-1.03), death (OR: 1.05, 95% CI: 1.03-1.06) during the 3-year
      follow-up period and overnight hospitalizations (incidence rate ratio [IRR]:
      1.02, 95% CI: 1.02-1.03) for an increase of 0.01 on the FI during the third year
      of follow-up. Measured by per standard deviation (SD) increment of the FI, the
      ORs were 1.21 and 1.40 for falls and death respectively, while the HR was 1.17
      for fractures and the IRR was 1.18 for overnight hospitalizations respectively.
      CONCLUSION: The FI of deficit accumulation increased with chronological age
      significantly. The FI was associated with and predicted increased risk of falls,
      fractures, death and overnight hospitalizations significantly.

PMID- 24885324
TI  - Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase
      inhibitor-associated musculoskeletal symptoms: a study protocol for a
      multicenter, randomized, controlled clinical trial.
AB  - BACKGROUND: Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine
      treatment in postmenopausal women with early-stage breast cancer. One of the main
      adverse effects of AIs is musculoskeletal symptoms, which leads to a lower
      quality of life and poor adherence to AI treatment. To date, no effective
      management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has
      been developed. METHODS/DESIGN: To determine whether the traditional Chinese
      medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct
      a multicenter, randomized, double-blind, placebo-controlled clinical trial.
      Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled
      and treated with traditional Chinese medicine or placebo for 12 weeks. The
      primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario
      and McMaster Universities Osteoarthritis Index, and Modified Score for the
      Assessment and Quantification of Chronic Rheumatoid Affections of the Hands,
      which will be obtained at baseline and at 4, 8, 12 and 24 weeks. DISCUSSION: The
      results of this study will provide a new strategy to help relieve AIMSS. TRIAL
      REGISTRATION ISCTN: ISRCTN06129599 (assigned 14 August 2013).

PMID- 24885325
TI  - RPM-1 is localized to distinct subcellular compartments and regulates axon length
      in GABAergic motor neurons.
AB  - BACKGROUND: The PAM/Highwire/RPM-1 (PHR) proteins are conserved signaling
      proteins that regulate axon length and synapse formation during development. Loss
      of function in Caenorhabditis elegans rpm-1 results in axon termination and
      synapse formation defects in the mechanosensory neurons. An explanation for why
      these two phenotypes are observed in a single neuronal cell has remained absent.
      Further, it is uncertain whether the axon termination phenotypes observed in the
      mechanosensory neurons of rpm-1 mutants are unique to this specific type of
      neuron, or more widespread defects that occur with loss of function in rpm-1.
      RESULTS: Here, we show that RPM-1 is localized to both the mature axon tip and
      the presynaptic terminals of individual motor neurons and individual
      mechanosensory neurons. Genetic analysis indicated that GABAergic motor neurons,
      like the mechanosensory neurons, have both synapse formation and axon termination
      defects in rpm-1 mutants. RPM-1 functions in parallel with the active zone
      component SYD-2 (Liprin) to regulate not only synapse formation, but also axon
      termination in motor neurons. Our analysis of rpm-1-/-; syd-2-/- double mutants
      also revealed a role for RPM-1 in axon extension. The MAP3K DLK-1 partly mediated
      RPM-1 function in both axon termination and axon extension, and the relative role
      of DLK-1 was dictated by the anatomical location of the neuron in question.
      CONCLUSIONS: Our findings show that axon termination defects are a core phenotype
      caused by loss of function in rpm-1, and not unique to the mechanosensory
      neurons. We show in motor neurons and in mechanosensory neurons that RPM-1 is
      localized to multiple, distinct subcellular compartments in a single cell. Thus,
      RPM-1 might be differentially regulated or RPM-1 might differentially control
      signals in distinct subcellular compartments to regulate multiple developmental
      outcomes in a single neuron. Our findings provide further support for the
      previously proposed model that PHR proteins function to coordinate axon outgrowth
      and termination with synapse formation.

PMID- 24885326
TI  - Endothelial function is impaired in conduit arteries of pannexin1 knockout mice.
AB  - Pannexin1 is ubiquitously expressed in vertebrate tissues, but the role it plays
      in vascular tone regulation remains unclear. We found that Pannexin1 expression
      level is much higher in the endothelium relative to smooth muscle of saphenous
      artery. The ability of endothelium-intact arteries for dilation was significantly
      impaired whereas contractile responses were considerably increased in mice with
      genetic ablation of Pannexin1. No such increased contractile responses were
      detected in the endothelium-denuded arteries. Combined, our findings suggest a
      new function of Pannexin1 as an important player in normal endothelium-dependent
      regulation of arterial tone, where it facilitates vessel dilation and attenuates
      constriction.

PMID- 24885327
TI  - Late toxicity and five year outcomes after high-dose-rate brachytherapy as a
      monotherapy for localized prostate cancer.
AB  - BACKGROUND: To determine the 5-year outcome after high-dose-rate brachytherapy
      (HDR-BT) as a monotherapy. METHODS: Between 10/2003 and 06/2006, 36 patients with
      low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT
      monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within
      48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received
      concomitant androgen deprivation therapy (ADT). Toxicity was scored according to
      the common terminology criteria for adverse events from the National Cancer
      Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to
      the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for
      late grade 3 GU toxicity were analyzed using univariate and multivariate Cox
      regression analyses. RESULTS: The median follow-up was 6.9 years (range, 1.5-8.0
      years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%)
      and 7 (19%) patients, respectively. The actuarial proportion of patients with
      late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3
      gastrointestinal (GI) toxicities were not observed. The crude erectile function
      preservation rate in patients without ADT was 75%. The 5 year biochemical
      recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was
      associated with the urethral volume (p = 0.001) and the urethral V120 (urethral
      volume receiving >=120% of the PD; p = 0.0005) after multivariate Cox regression.
      CONCLUSIONS: After HDR-BT monotherapy late grade 3 GU was observed relatively
      frequently and was associated with the urethral V120. GI toxicity was negligible,
      the erectile function preservation rate and the bRFS rate was excellent.

PMID- 24885328
TI  - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in
      mice.
AB  - BACKGROUND: Human papillomaviruses (HPV) are the causative agents of cervical
      cancer in women, which results in over 250 000 deaths per year. Presently there
      are two prophylactic vaccines on the market, protecting against the two most
      common high-risk HPV types 16 and 18. These vaccines remain very expensive and
      are not generally affordable in developing countries where they are needed most.
      Additionally, there remains a need to treat women that are already infected with
      HPV, and who have high-grade lesions or cervical cancer. METHODS: In this paper,
      we characterize the immunogenicity of a therapeutic vaccine that targets the E7
      protein of the most prevalent high-risk HPV - type 16 - the gene which has
      previously been shown to be effective in DNA vaccine trials in mice. The
      synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but
      retains all naturally-occurring CTL epitopes. This was genetically fused to
      Zera(r), a self-assembly domain of the maize gamma-zein able to induce the
      accumulation of recombinant proteins into protein bodies (PBs), within the
      endoplasmic reticulum in a number of expression systems. RESULTS: High-level
      expression of the HPV 16E7SH protein fused to Zera(r) in plants was achieved, and
      the protein bodies could be easily and cost-effectively purified. Immune
      responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine
      model, with the protein vaccine successfully inducing a specific humoral as well
      as cell mediated immune response, and mediating tumour regression. CONCLUSIONS:
      The fusion of 16E7SH to the Zera(r) peptide was found to enhance the immune
      responses, presumably by means of a more efficient antigen presentation via the
      protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also
      enhanced immune responses, indicating an adjuvant activity for the Zera(r) PBs.

PMID- 24885330
TI  - The role of simulation in developing communication and gestural skills in medical
      students.
AB  - BACKGROUND: International studies have shown that laboratory training,
      particularly through the application of the principles of simulation learning, is
      an effective means of developing the communication and gestural skills of
      healthcare professionals. At the Advanced Simulation Center of the University of
      Genoa we have therefore established the first clinical skill laboratory with
      medical school students and an interprofessional team of trainers, as the first
      step towards developing simulation training of both medical and nursing students
      at our University.The aim of this study was to assess student satisfaction with
      laboratory training in an Advanced Simulation Center. METHODS: All of the third
      year students of the Medical School (n = 261) were invited to participate in the
      laboratory sessions at the Advanced Simulation Center. They were divided into
      groups and attended the Center for one week. The team of trainers included
      medical doctors and nurses involved in teaching at the University Medicine and
      Nursing programs. At the end of the week, the students were administered an
      anonymous questionnaire made up of two sections: the first one was on the content
      of individual laboratory sessions; the second on the training methods, materials
      used and the trainers. A five-point Likert scale was used to measure
      satisfaction. RESULTS: According to the students all of the topics covered by the
      laboratory sessions were irreplaceable. Questionnaire results showed a high level
      of satisfaction with the methods used, the instruments developed, and with the
      expertise and approachability of the educators. Almost all of the students wanted
      to participate in similar laboratory activities in the future. CONCLUSIONS: The
      study highlighted the need to permanently integrate laboratory training sessions
      into the curriculum of medical students, who found them very useful and
      stimulating. The limit of this study was that only the teaching staff was
      interprofessional, and the students were only 3rd Year students of medicine.In
      the future, we hope to include also nursing students because they will need to
      learn how to deal with aspects of their clinical practice that require an
      interprofessional approach.

PMID- 24885329
TI  - Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase
      D family protein as a novel virulence factor.
AB  - BACKGROUND: Klebsiella pneumoniae strains are pathogenic to animals and humans,
      in which they are both a frequent cause of nosocomial infections and a re
      emerging cause of severe community-acquired infections. K. pneumoniae isolates of
      the capsular serotype K2 are among the most virulent. In order to identify novel
      putative virulence factors that may account for the severity of K2 infections,
      the genome sequence of the K2 reference strain Kp52.145 was determined and
      compared to two K1 and K2 strains of low virulence and to the reference strains
      MGH 78578 and NTUH-K2044. RESULTS: In addition to diverse functions related to
      host colonization and virulence encoded in genomic regions common to the four
      strains, four genomic islands specific for Kp52.145 were identified. These
      regions encoded genes for the synthesis of colibactin toxin, a putative cytotoxin
      outer membrane protein, secretion systems, nucleases and eukaryotic-like
      proteins. In addition, an insertion within a type VI secretion system locus
      included sel1 domain containing proteins and a phospholipase D family protein
      (PLD1). The pld1 mutant was avirulent in a pneumonia model in mouse. The pld1
      mRNA was expressed in vivo and the pld1 gene was associated with K. pneumoniae
      isolates from severe infections. Analysis of lipid composition of a defective E.
      coli strain complemented with pld1 suggests an involvement of PLD1 in cardiolipin
      metabolism. CONCLUSIONS: Determination of the complete genome of the K2 reference
      strain identified several genomic islands comprising putative elements of
      pathogenicity. The role of PLD1 in pathogenesis was demonstrated for the first
      time and suggests that lipid metabolism is a novel virulence mechanism of K.
      pneumoniae.

PMID- 24885331
TI  - Identification of natural antimicrobial agents to treat dengue infection: In
      vitro analysis of latarcin peptide activity against dengue virus.
AB  - BACKGROUND: Although there have been considerable advances in the study of dengue
      virus, no vaccines or anti-dengue drugs are currently available for humans.
      Therefore, new approaches are necessary for the development of potent anti-dengue
      drugs. Natural antimicrobial peptides (AMPs) with potent antiviral activities are
      potential hits-to-leads for antiviral drug discovery. We performed this study to
      identify and characterise the inhibitory potential of the latarcin peptide (Ltc
      1, SMWSGMWRRKLKKLRNALKKKLKGE) against dengue virus replication in infected cells.
      RESULTS: The Ltc 1 peptide showed a significantly inhibitory effect against the
      dengue protease NS2B-NS3pro at 37 degrees C, a physiological human temperature,
      (IC50, 12.68 +/- 3.2 MUM), and greater inhibitory effect was observed at 40
      degrees C, a temperature similar to a high fever (IC50, 6.58 +/- 4.1 MUM). A
      greater reduction in viral load (p.f.u./ml) was observed at simultaneous (0.7 +/-
      0.3 vs. 7.2 +/- 0.5 control) and post-treatment (1.8 +/- 0.7 vs. 6.8 +/- 0.6
      control) compared to the pre-treatment (4.5 +/- 0.6 vs. 6.9 +/- 0.5 control).
      Treatment with the Ltc 1 peptide reduced the viral RNA in a dose-dependent manner
      with EC50 values of 8.3 +/- 1.2, 7.6 +/- 2.7 and 6.8 +/- 2.5 MUM at 24, 48 and 72
      h, respectively. CONCLUSIONS: The Ltc 1 peptide exhibited significant inhibitory
      effects against dengue NS2B-NS3pro and virus replication in the infected cells.
      Therefore, further investigation is necessary to develop the Ltc 1 peptide as a
      new anti-dengue therapeutic.

PMID- 24885332
TI  - Unintentional injury and its prevention in infant: knowledge and self-reported
      practices of main caregivers.
AB  - BACKGROUND: Unintentional injuries are the major cause of morbidity and mortality
      in infants. Prevention of unintentional injuries has been shown to be effective
      with education. Understanding the level of knowledge and practices of caregivers
      in infant safety would be useful to identify gaps for improvement. METHODS: A
      cross-sectional study was conducted in an urban government health clinic in
      Malaysia among main caregivers of infants aged 11 to 15 months. Face-to-face
      interviews were conducted using a semi-structured self-designed questionnaire.
      Responses to the items were categorised by the percentage of correct answers:
      poor (<50%), moderate (50% - 70%) and good (>70%). RESULTS: A total of 403
      caregivers participated in the study. Of the 21 items in the questionnaire on
      knowledge, 19 had good-to-moderate responses and two had poor responses. The two
      items on knowledge with poor responses were on the use of infant walkers (26.8%)
      and allowing infants on motorcycles as pillion riders (27.3%). Self-reported
      practice of infant safety was poor. None of the participants followed all 19
      safety practices measured. Eight (42.1%) items on self-reported practices had
      poor responses. The worst three of these were on the use of baby cots (16.4%),
      avoiding the use of infant walkers (23.8%) and putting infants to sleep in the
      supine position (25.6%). Better knowledge was associated with self-reported
      safety practices in infants (p < 0.05). However, knowledge did not correspond to
      correct practice, particularly on the use of baby cots, infant walkers and sarong
      cradles. CONCLUSION: Main caregivers' knowledge on infant safety was good but
      self-reported practice was poor. Further research in the future is required to
      identify interventions that target these potentially harmful practices.

PMID- 24885333
TI  - Coexistence of aneurysmal subarachnoid hemorrhage and surgically identified
      pituitary apoplexy: a case report and review of the literature.
AB  - INTRODUCTION: A ruptured aneurysm associated with a pituitary apoplexy is rare.
      We present the first case report of the coexistence of a ruptured posterior
      communicating aneurysm with a surgically discovered pituitary apoplexy where the
      pituitary apoplexy had not been diagnosed by a pre-operative computerized
      tomography scan. CASE PRESENTATION: A 31-year-old right-handed Chinese woman
      began to experience severe headache, vomiting and blurred vision which continued
      for two days. On admission to the hospital, a brain computerized tomography scan
      demonstrated a small amount of increased signal in the basal cisterns; no
      evidence of intrasellar and suprasellar lesions was seen. The appearance of her
      brain suggested aneurysmal subarachnoid hemorrhage. She had nuchal rigidity and
      reduced vision. There was no extra-ocular palsy and no other neurological
      deficit. Our patient had no stigmata of Cushing's syndrome or acromegaly. During
      an interview for further history, she reported normal menses and denied reduced
      vision.Cerebral digital subtraction angiography was subsequently performed, which
      revealed a 6mm left posterior communicating aneurysm. Urgent left pterional
      craniotomy was performed. The left ruptured posterior communicating artery
      aneurysm was completely dissected prior to clipping. At surgery, a suprasellar
      mass was discovered, the tumor bulging the diaphragma sella and projecting
      anteriorly under the chiasm raising suspicion of a pituitary tumor. The anterior
      part of the tumor capsule was opened and a necrotic tumor mixed with dark old
      blood was removed. The appearance suggested pituitary apoplexy.Histopathology
      revealed pituitary adenoma with evidence of hemorrhagic necrosis. Our patient
      made a good recovery. CONCLUSION: Our case report proves that pituitary apoplexy
      can be coexistent with the rupture of a posterior communicating aneurysm. This
      association should be considered when evaluating any case of aneurysm. A normal
      computerized tomography scan does not exclude pituitary apoplexy. Pre-operative
      magnetic resonance imaging interpretation is required if a pituitary apoplexy is
      suspected. Craniotomy allows a coexisting aneurysm and pituitary apoplexy to be
      simultaneously treated.

PMID- 24885335
TI  - Optimization of linkage mapping strategy and construction of a high-density
      American lotus linkage map.
AB  - BACKGROUND: Lotus is a diploid plant with agricultural, medicinal, and ecological
      significance. Genetic linkage maps are fundamental resources for genome and
      genetic study, and also provide molecular markers for breeding in agriculturally
      important species. Genotyping by sequencing revolutionized genetic mapping, the
      restriction-site associated DNA sequencing (RADseq) allowed rapid discovery of
      thousands of SNPs markers, and a crucial aspect of the sequence based mapping
      strategy is the reference sequences used for marker identification. RESULTS: We
      assessed the effectiveness of linkage mapping using three types of references for
      scoring markers: the unmasked genome, repeat masked genome, and gene models.
      Overall, the repeat masked genome produced the optimal genetic maps. A high
      density genetic map of American lotus was constructed using an F1 population
      derived from a cross between Nelumbo nucifera 'China Antique' and N. lutea 'AL1'.
      A total of 4,098 RADseq markers were used to construct the American lotus 'AL1'
      genetic map, and 147 markers were used to construct the Chinese lotus 'China
      Antique' genetic map. The American lotus map has 9 linkage groups, and spans
      494.3 cM, with an average distance of 0.7 cM between adjacent markers. The
      American lotus map was used to anchor scaffold sequences in the N. nucifera
      'China Antique' draft genome. 3,603 RADseq markers anchored 234 individual
      scaffold sequences into 9 megascaffolds spanning 67% of the 804 Mb draft genome.
      CONCLUSIONS: Among the unmasked genome, repeat masked genome and gene models, the
      optimal reference sequences to call RADseq markers for map construction is repeat
      masked genome. This high density genetic map is a valuable resource for genomic
      research and crop improvement in lotus.

PMID- 24885334
TI  - A study of antioxidant activity, enzymatic inhibition and in vitro toxicity of
      selected traditional Sudanese plants with anti-diabetic potential.
AB  - BACKGROUND: Diabetes mellitus is a chronic metabolic disease with life
      threatening complications. Despite the enormous progress in conventional medicine
      and pharmaceutical industry, herbal-based medicines are still a common practice
      for the treatment of diabetes. This study evaluated ethanolic and aqueous
      extracts of selected Sudanese plants that are traditionally used to treat
      diabetes. METHODS: Extraction was carried out according to method described by
      Sukhdev et. al. and the extracts were tested for their glycogen phosphorylase
      inhibition, Brine shrimp lethality and antioxidant activity using (DPPH) radical
      scavenging activity and iron chelating activity. Extracts prepared from the
      leaves of Ambrosia maritima, fruits of Foeniculum vulgare and Ammi visnaga,
      exudates of Acacia Senegal, and seeds of Sesamum indicum and Nigella sativa.
      RESULTS: Nigella sativa ethanolic extract showed no toxicity on Brine shrimp
      Lethality Test, while its aqueous extract was toxic. All other extracts were
      highly toxic and ethanolic extracts of Foeniculum vulgare exhibited the highest
      toxicity. All plant extracts with exception of Acacia senegal revealed
      significant antioxidant activity in DPPH free radical scavenging assay.
      CONCLUSIONS: These results highly agree with the ethnobotanical uses of these
      plants as antidiabetic. This study endorses further studies on plants
      investigated, to determine their potential for type 2 diabetes management.
      Moreover isolation and identification of active compounds are highly recommended.

PMID- 24885336
TI  - Health care utilization for acute illnesses in an urban setting with a refugee
      population in Nairobi, Kenya: a cross-sectional survey.
AB  - BACKGROUND: Estimates place the number of refugees in Nairobi over 100,000. The
      constant movement of refugees between countries of origin, refugee camps, and
      Nairobi poses risk of introduction and transmission of communicable diseases into
      Kenya. We assessed the care-seeking behavior of residents of Eastleigh, a
      neighborhood in Nairobi with urban refugees. METHODS: During July and August
      2010, we conducted a Health Utilization Survey in Section II of Eastleigh. We
      used a multistage random cluster sampling design to identify households for
      interview. A standard questionnaire on the household demographics, water and
      sanitation was administered to household caretakers. Separate questionnaires were
      administered to household members who had one or more of the illnesses of
      interest. RESULTS: Of 785 households targeted for interview, data were obtained
      from 673 (85.7%) households with 3,005 residents. Of the surveyed respondents,
      290 (9.7%) individuals reported acute respiratory illness (ARI) in the previous
      12 months, 222 (7.4%) reported fever in the preceding 2 weeks, and 54 (1.8%)
      reported having diarrhea in the 30 days prior to the survey. Children <5 years
      old had the highest frequency of all the illnesses surveyed: 17.1% (95% CI 12.2
      21.9) reported ARI, 10.0% (95% CI 6.2-13.8) reported fever, and 6.9% (3.8-10.0)
      reported diarrhea during the time periods specified for each syndrome. Twenty
      nine [7.5% (95% CI 4.3-10.7)] hospitalizations were reported among all age groups
      of those who sought care. Among participants who reported >=1 illness, 330
      (77.0%) sought some form of health care; most (174 [59.8%]) sought health care
      services from private health care providers. Fifty-five (18.9%) participants
      seeking healthcare services visited a pharmacy. Few residents of Eastleigh (38
      [13.1%]) sought care at government-run facilities, and 24 (8.2%) sought care from
      a relative, a religious leader, or a health volunteer. Of those who did not seek
      any health care services (99 [23.0%]), the primary reason was cost (44.8%),
      followed by belief that the person was not sick enough (34.6%). CONCLUSION:
      Health care utilization in Eastleigh is high; however, a large proportion of
      residents opt to seek care at private clinics or pharmacies, despite the
      availability of accessible government-provided health care services in this area.

PMID- 24885338
TI  - Interpretation and identification of causal mediation.
AB  - This article reviews the foundations of causal mediation analysis and offers a
      general and transparent account of the conditions necessary for the
      identification of natural direct and indirect effects, thus facilitating a more
      informed judgment of the plausibility of these conditions in specific
      applications. I show that the conditions usually cited in the literature are
      overly restrictive and can be relaxed substantially without compromising
      identification. In particular, I show that natural effects can be identified by
      methods that go beyond standard adjustment for confounders, applicable to
      observational studies in which treatment assignment remains confounded with the
      mediator or with the outcome. These identification conditions can be validated
      algorithmically from the diagrammatic description of one's model and are
      guaranteed to produce unbiased results whenever the description is correct. The
      identification conditions can be further relaxed in parametric models, possibly
      including interactions, and permit one to compare the relative importance of
      several pathways, mediated by interdependent variables.

PMID- 24885337
TI  - Schwann-like cells seeded in acellular nerve grafts improve nerve regeneration.
AB  - BACKGROUND: This study evaluated whether Schwann-like cells (SLCs) induced from
      bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into acellular
      nerve grafts (ANGs) could repair nerve defects compared with nerve isografts and
      ANGs with BM-MSCs. METHODS: BM-MSCs extracted, separated and purified from the
      bone marrow of rats, and some of the BM-MSCs were cultured with mixed induction
      agents that could induce BM-MSCs into SLCs. Either SLCs or BM-MSCs were seeded
      onto 10-mm ANGs, and the isografts were chosen as the control. The walking-track
      test, tibialis anterior muscle weight measurement, electrophysiological
      examination, toluidine blue staining, transmission electron micrographs and
      immunostaining of S-100 and VEGF in these three groups were evaluated in a 10-mm
      rat sciatic injury-repair model. RESULTS: The walking-track test, tibialis
      anterior muscle weight measurement and electrophysiological examination of the
      sciatic nerve suggested the groups of ANGs with SLCs and isografts obtained
      better results than the BM-MSC group (P<0.05). Meanwhile, the results of the SLCs
      and isograft groups were similar (P>0.05). All the histomorphometric analyses
      (toluidine blue staining, transmission electron micrographs and immunostaining of
      S-100 and VEGF) showed that there were more regenerating nerve fibers in the
      group of ANGs with SLCs than the BM-MSCs (P<0.05), but there was no significant
      difference between the SLC and isograft groups (P>0.05). CONCLUSIONS: SLCs seeded
      in ANGs and isografts show better functional regeneration compared with BM-MSCs
      seeded in ANGs. Additionally, SLCs combined with ANGs present almost the same
      outcome as the isografts. Therefore, SLCs with ANGs can be a good choice in nerve
      defect repairs.

PMID- 24885339
TI  - How bandwidth selection algorithms impact exploratory data analysis using kernel
      density estimation.
AB  - Exploratory data analysis (EDA) can reveal important features of underlying
      distributions, and these features often have an impact on inferences and
      conclusions drawn from data. Graphical analysis is central to EDA, and graphical
      representations of distributions often benefit from smoothing. A viable method of
      estimating and graphing the underlying density in EDA is kernel density
      estimation (KDE). This article provides an introduction to KDE and examines
      alternative methods for specifying the smoothing bandwidth in terms of their
      ability to recover the true density. We also illustrate the comparison and use of
      KDE methods with 2 empirical examples. Simulations were carried out in which we
      compared 8 bandwidth selection methods (Sheather-Jones plug-in [SJDP], normal
      rule of thumb, Silverman's rule of thumb, least squares cross-validation, biased
      cross-validation, and 3 adaptive kernel estimators) using 5 true density shapes
      (standard normal, positively skewed, bimodal, skewed bimodal, and standard
      lognormal) and 9 sample sizes (15, 25, 50, 75, 100, 250, 500, 1,000, 2,000).
      Results indicate that, overall, SJDP outperformed all methods. However, for
      smaller sample sizes (25 to 100) either biased cross-validation or Silverman's
      rule of thumb was recommended, and for larger sample sizes the adaptive kernel
      estimator with SJDP was recommended. Information is provided about implementing
      the recommendations in the R computing language.

PMID- 24885340
TI  - Modeling latent growth with multiple indicators: a comparison of three
      approaches.
AB  - Latent growth curve models (LGCMs) are widely used methods for analyzing change
      in psychology and the social sciences. To date, most applications use first-order
      (single-indicator) LGCMs. These models have several limitations that can be
      overcome with multiple-indicator LGCMs. Currently, almost all multiple-indicator
      applications use the so-called second-order growth model (SGM; McArdle, 1988). In
      this article, we review the SGM and discuss 2 alternative, but less well-known,
      multiple-indicator LGCMs that overcome some of the limitations of the SGM: the
      generalized second-order growth model (GSGM) and the indicator-specific growth
      model (ISGM). In contrast to the SGM, the GSGM does not involve a proportionality
      constraint on the ratio of general to specific variance. The ISGM allows
      researchers to model indicator-specific growth. Both of these alternative models
      allow testing measurement invariance across time for state-variability
      components. We also present an empirical application regarding changes in self
      reported levels of anxiety and discuss implications of the differences between
      the 3 models for applied research.

PMID- 24885341
TI  - An introduction to modeling longitudinal data with generalized additive models:
      applications to single-case designs.
AB  - Single-case designs (SCDs) are short time series that assess intervention effects
      by measuring units repeatedly over time in both the presence and absence of
      treatment. This article introduces a statistical technique for analyzing SCD data
      that has not been much used in psychological and educational research:
      generalized additive models (GAMs). In parametric regression, the researcher must
      choose a functional form to impose on the data, for example, that trend over time
      is linear. GAMs reverse this process by letting the data inform the choice of
      functional form. In this article we review the problem that trend poses in SCDs,
      discuss how current SCD analytic methods approach trend, describe GAMs as a
      possible solution, suggest a GAM model testing procedure for examining the
      presence of trend in SCDs, present a small simulation to show the statistical
      properties of GAMs, and illustrate the procedure on 3 examples of different
      lengths. Results suggest that GAMs may be very useful both as a form of
      sensitivity analysis for checking the plausibility of assumptions about trend and
      as a primary data analysis strategy for testing treatment effects. We conclude
      with a discussion of some problems with GAMs and some future directions for
      research on the application of GAMs to SCDs.

PMID- 24885342
TI  - De novo deletion of chromosome 11q12.3 in monozygotic twins affected by Poland
      Syndrome.
AB  - BACKGROUND: Poland Syndrome (PS) is a rare disorder characterized by
      hypoplasia/aplasia of the pectoralis major muscle, variably associated with
      thoracic and upper limb anomalies. Familial recurrence has been reported
      indicating that PS could have a genetic basis, though the genetic mechanisms
      underlying PS development are still unknown. CASE PRESENTATION: Here we describe
      a couple of monozygotic (MZ) twin girls, both presenting with Poland Syndrome.
      They carry a de novo heterozygous 126 Kbp deletion at chromosome 11q12.3
      involving 5 genes, four of which, namely HRASLS5, RARRES3, HRASLS2, and PLA2G16,
      encode proteins that regulate cellular growth, differentiation, and apoptosis,
      mainly through Ras-mediated signaling pathways. CONCLUSIONS: Phenotype
      concordance between the monozygotic twin probands provides evidence supporting
      the genetic control of PS. As genes controlling cell growth and differentiation
      may be related to morphological defects originating during development, we
      postulate that the observed chromosome deletion could be causative of the
      phenotype observed in the twin girls and the deleted genes could play a role in
      PS development.

PMID- 24885343
TI  - Spatial heterogeneity of type I error for local cluster detection tests.
AB  - BACKGROUND: Just as power, type I error of cluster detection tests (CDTs) should
      be spatially assessed. Indeed, CDTs' type I error and power have both a spatial
      component as CDTs both detect and locate clusters. In the case of type I error,
      the spatial distribution of wrongly detected clusters (WDCs) can be particularly
      affected by edge effect. This simulation study aims to describe the spatial
      distribution of WDCs and to confirm and quantify the presence of edge effect.
      METHODS: A simulation of 40 000 datasets has been performed under the null
      hypothesis of risk homogeneity. The simulation design used realistic parameters
      from survey data on birth defects, and in particular, two baseline risks. The
      simulated datasets were analyzed using the Kulldorff's spatial scan as a commonly
      used test whose behavior is otherwise well known. To describe the spatial
      distribution of type I error, we defined the participation rate for each spatial
      unit of the region. We used this indicator in a new statistical test proposed to
      confirm, as well as quantify, the edge effect. RESULTS: The predefined type I
      error of 5% was respected for both baseline risks. Results showed strong edge
      effect in participation rates, with a descending gradient from center to edge,
      and WDCs more often centrally situated. CONCLUSIONS: In routine analysis of real
      data, clusters on the edge of the region should be carefully considered as they
      rarely occur when there is no cluster. Further work is needed to combine results
      from power studies with this work in order to optimize CDTs performance.

PMID- 24885344
TI  - A preliminary evaluation of antihyperglycemic and analgesic activity of
      Alternanthera sessilis aerial parts.
AB  - BACKGROUND: Alternanthera sessilis is used by folk medicinal practitioners of
      Bangladesh for alleviation of severe pain. The objective of this study was to
      scientifically analyze the analgesic (non-narcotic) property of aerial parts of
      the plant along with antihyperglycemic activity. METHODS: Antihyperglycemic
      activity was measured by oral glucose tolerance tests. Analgesic (non-narcotic)
      activity was determined by observed decreases in abdominal writhings in
      intraperitoneally administered acetic acid-induced pain model in mice. RESULTS:
      Administration of methanol extract of aerial parts led to dose-dependent and
      significant reductions in blood glucose levels in glucose-loaded mice. At doses
      of 50, 100, 200 and 400 mg per kg body weight, the extract reduced blood sugar
      levels by 22.9, 30.7, 45.4 and 46.1%, respectively compared to control animals.
      By comparison, a standard antihyperglycemic drug, glibenclamide, when
      administered at a dose of 10 mg per kg body weight, reduced blood glucose level
      by 48.9%. In analgesic activity tests, the extract at the above four doses
      reduced the number of abdominal writhings by 27.6, 37.9, 41.4, and 44.8%,
      respectively. A standard analgesic drug, aspirin, reduced the number of writhings
      by 31.0 and 51.7%, respectively, when administered at doses of 200 and 400 mg per
      kg body weight. CONCLUSION: The results validate the folk medicinal use of the
      plant to alleviate pain. At the same time, the antihyperglycemic activity result
      suggests that the plant may be a potential source for blood sugar lowering
      drug(s).

PMID- 24885345
TI  - Small non-coding RNA signature in multiple sclerosis patients after treatment
      with interferon-beta.
AB  - BACKGROUND: Non-coding small RNA molecules play pivotal roles in cellular and
      developmental processes by regulating gene expression at the post-transcriptional
      level. In human diseases, the roles of the non-coding small RNAs in specific
      degradation or translational suppression of the targeted mRNAs suggest a
      potential therapeutic approach of post-transcriptional gene silencing that
      targets the underlying disease etiology. The involvement of non-coding small RNAs
      in the pathogenesis of neurodegenerative diseases such as Alzheimer's ,
      Parkinson's disease and Multiple Sclerosis has been demonstrated. Multiple
      sclerosis (MS) is an autoimmune disease of the central nervous system,
      characterized by chronic inflammation, demyelination and scarring as well as a
      broad spectrum of signs and symptoms. The current standard treatment for SM is
      interferon beta (IFNbeta) that is less than ideal due to side effects. In this
      study we administered the standard IFN-beta treatment to Relapsing-Remitting MS
      patients, all responder to the therapy; then examined their sncRNA expression
      profiles in order to identify the ncRNAs that were associated with MS patients'
      response to IFNbeta. METHODS: 40 IFNbeta treated Relapsing-Remitting MS patients
      were enrolled. We analyzed the composition of the entire small transcriptome by a
      small RNA cloning method, using peripheral blood from Relapsing-Remitting MS
      patients at baseline and 3 and 6 months after the start of IFNbeta therapy. Real
      time qPCR from the same patients group and from 20 additional patients was
      performed to profile miRNAs expression. RESULTS: Beside the altered expression of
      several miRNAs, our analyses revealed the differential expression of small
      nucleolar RNAs and misc-RNAs.For the first time, we found that the expression
      level of miR-26a-5p changed related to INF-beta response. MiR-26a-5p expression
      was significantly higher in IFN-beta treated RRMS patients at 3 months treatment,
      keeping quite stable at 6 months treatments. CONCLUSIONS: Our results might
      provide insights into the mechanisms of action of IFN-beta treatment in MS and
      provide fundamentals for the development of new biomarkers and/or therapeutic
      tools.

PMID- 24885346
TI  - Alcohol brief interventions in Scottish antenatal care: a qualitative study of
      midwives' attitudes and practices.
AB  - BACKGROUND: Infants exposed to alcohol in the womb are at increased risk of
      experiencing health problems. However, mixed messages about the consequences of
      prenatal alcohol consumption have resulted in inconsistent attitudes and
      practices amongst some healthcare practitioners. Screening and alcohol brief
      interventions (ABIs) can reduce risky drinking in various clinical settings.
      Recently, a program of screening and ABIs have been implemented in antenatal care
      settings in Scotland. However, current evidence suggests that midwives'
      involvement in alcohol brief interventions activities is patchy. This study
      explored midwives' attitudes and practices regarding alcohol screening and ABIs
      in order to understand why they are relatively underutilized in antenatal care
      settings compared to other clinical settings. METHODS: This was a qualitative
      study, involving semi-structured interviews with 15 midwives and a focus group
      with a further six midwifery team leaders (21 participants in total) in Scotland.
      Interview transcripts were analysed using thematic analysis. RESULTS: Midwives
      were positive about their involvement in the screening and ABI program. However,
      they were not completely convinced about the purpose and value of the screening
      and ABIs in antenatal care. In the midst of competing priorities, the program was
      seen as having a low priority in their workload. Midwives felt that the rapport
      between them and pregnant women was not sufficiently established at the first
      antenatal appointment to allow them to discuss alcohol issues appropriately. They
      reported that many women had already given up drinking or were drinking minimal
      amounts prior to the first antenatal appointment. CONCLUSIONS: Midwives
      recognised the important role they could play in alcohol intervention activities
      in antenatal care. As the majority of women stop consuming alcohol in pregnancy,
      many will not need an ABI. Those who have not stopped are likely to need an ABI,
      but midwives were concerned that it was this group that they were most likely to
      alienate by discussing such concerns. Further consideration should be given to
      pre-pregnancy preventative measures as they are more likely to reduce alcohol
      exposed pregnancies.

PMID- 24885347
TI  - Silicon substrate as a novel cell culture device for myoblast cells.
AB  - BACKGROUND: Tissue and organ regeneration via transplantation of cell bodies in
      situ has become an interesting strategy in regenerative medicine. Developments of
      cell carriers to systematically deliver cell bodies in the damage site have fall
      shorten on effectively meet this purpose due to inappropriate release control.
      Thus, there is still need of novel substrate to achieve targeted cell delivery
      with appropriate vehicles. In the present study, silicon based photovoltaic (PV)
      devices are used as a cell culturing substrate for the expansion of myoblast
      mouse cell (C2C12 cells) that offers an atmosphere for regular cell growth in
      vitro. The adherence, viability and proliferation of the cells on the silicon
      surface were examined by direct cell counting and fluorescence microscopy.
      RESULTS: It was found that on the silicon surface, cells proliferated over 7 days
      showing normal morphology, and expressed their biological activities. Cell
      culture on silicon substrate reveals their attachment and proliferation over the
      surface of the PV device. After first day of culture, cell viability was 88% and
      cell survival remained above 86% as compared to the seeding day after the seventh
      day. Furthermore, the DAPI staining revealed that the initially scattered cells
      were able to eventually build a cellular monolayer on top of the silicon
      substrate. CONCLUSIONS: This study explored the biological applications of
      silicon based PV devices, demonstrating its biocompatibility properties and found
      useful for culture of cells on porous 2-D surface. The incorporation of silicon
      substrate has been efficaciously revealed as a potential cell carrier or vehicle
      in cell growth technology, allowing for their use in cell based gene therapy,
      tissue engineering, and therapeutic angiogenesis.

PMID- 24885348
TI  - Super-reduced polyoxometalates: excellent molecular cluster battery components
      and semipermeable molecular capacitors.
AB  - Theoretical investigations are presented on the molecular and electronic
      structure changes that occur as alpha-Keggin-type polyoxometalate (POM(3-))
      clusters [PM12O40](3-) (M = Mo, W) are converted toward their super-reduced
      POM(27-) state during the discharging process in lithium-based molecular cluster
      batteries. Density functional theory was employed in geometry optimization, and
      first-principles molecular dynamics simulations were used to explore local minima
      on the potential energy surface of neutral POM clusters adorned with randomly
      placed Li atoms as electron donors around the cluster surface. On the basis of
      structural, electron density, and molecular orbital studies, we present evidence
      that the super-reduction is accompanied by metal-metal bond formation, beginning
      from the 12th to 14th excess electron transferred to the cluster. Afterward, the
      number of metal-metal bonds increases nearly linearly with the number of
      additionally transferred excess electrons. In alpha-Keggin-type POMs, metal
      triangles are a prominently emerging structural feature. The origin of the metal
      triangle formation during super-reduction stems from the formation of
      characteristic three-center two-electron bonds in triangular metal atom sites,
      created under preservation of the POM skeleton via "squeezing out" of oxygen
      atoms bridging two metal atoms when the underlying metal atoms form covalent
      bonds. The driving force for this unusual geometrical and electronic structure
      change is a local Jahn-Teller distortion at individual transition-metal
      octahedral sites, where the triply degenerate t2 d orbitals become partially
      filled during reduction and gain energy by distortion of the octahedron in such a
      way that metal-metal bonds are formed. The bonding orbitals show strong
      contributions from mixing with metal-oxygen antibonding orbitals, thereby
      "shuffling away" excess electrons from the cluster center to the outside of the
      cage. The high density of negatively charged yet largely separated oxygen atoms
      on the surface of the super-reduced POM(27-) polyanion allows the huge Coulombic
      repulsion due to the presence of the excess electrons to be counterbalanced by
      the presence of Li countercations, which partially penetrate into the outer
      oxygen shell. This "semiporous molecular capacitor" structure is likely the
      reason for the effective electron uptake in POMs. 

PMID- 24885351
TI  - Detection of Clostridium difficile infection clusters, using the temporal scan
      statistic, in a community hospital in southern Ontario, Canada, 2006-2011.
AB  - BACKGROUND: In hospitals, Clostridium difficile infection (CDI) surveillance
      relies on unvalidated guidelines or threshold criteria to identify outbreaks.
      This can result in false-positive and -negative cluster alarms. The application
      of statistical methods to identify and understand CDI clusters may be a useful
      alternative or complement to standard surveillance techniques. The objectives of
      this study were to investigate the utility of the temporal scan statistic for
      detecting CDI clusters and determine if there are significant differences in the
      rate of CDI cases by month, season, and year in a community hospital. METHODS:
      Bacteriology reports of patients identified with a CDI from August 2006 to
      February 2011 were collected. For patients detected with CDI from March 2010 to
      February 2011, stool specimens were obtained. Clostridium difficile isolates were
      characterized by ribotyping and investigated for the presence of toxin genes by
      PCR. CDI clusters were investigated using a retrospective temporal scan test
      statistic. Statistically significant clusters were compared to known CDI
      outbreaks within the hospital. A negative binomial regression model was used to
      identify associations between year, season, month and the rate of CDI cases.
      RESULTS: Overall, 86 CDI cases were identified. Eighteen specimens were analyzed
      and nine ribotypes were classified with ribotype 027 (n = 6) the most prevalent.
      The temporal scan statistic identified significant CDI clusters at the hospital
      (n = 5), service (n = 6), and ward (n = 4) levels (P <= 0.05). Three clusters
      were concordant with the one C. difficile outbreak identified by hospital
      personnel. Two clusters were identified as potential outbreaks. The negative
      binomial model indicated years 2007-2010 (P <= 0.05) had decreased CDI rates
      compared to 2006 and spring had an increased CDI rate compared to the fall (P =
      0.023). CONCLUSIONS: Application of the temporal scan statistic identified
      several clusters, including potential outbreaks not detected by hospital
      personnel. The identification of time periods with decreased or increased CDI
      rates may have been a result of specific hospital events. Understanding the
      clustering of CDIs can aid in the interpretation of surveillance data and lead to
      the development of better early detection systems.

PMID- 24885349
TI  - Why do mothers encourage their children to control their weight? A cross
      sectional study of possible contributing factors.
AB  - BACKGROUND: Mothers encouraging their children to control their weight is
      problematic as it is associated with children's body dissatisfaction and weight
      concerns as well as further weight gain. The aim of this study was to identify
      factors in children and mothers associated with mothers encouraging their
      children to control their weight and possible gender differences therein.
      METHODS: Cross-sectional questionnaire data was available from 1658 mothers of
      primary school children (mean age 7.1 +/-0.6 years, 50.4% boys) participating in
      the Baden-Wurttemberg Study. Children's body weight and height were measured in a
      standardised manner. Logistic regressions were computed separately for boys and
      girls, adjusted odds ratios (OR) and 95% confidence intervals (CI) from the final
      model are reported. RESULTS: 29% of children were encouraged by their mothers,
      girls (32.4%) significantly more often than boys (25.6%). Child BMI (girls OR
      1.77, CI 1.57 to 1.99; boys OR 1.88, CI 1.66 to 2.13), and child migration
      background (girls OR 2.14, CI 1.45 to 3.16; boys OR 1.60, CI 1.07 to 2.37) were
      significantly associated with encouragement by mothers. For girls, maternal body
      dissatisfaction (OR 1.59, CI 1.10 to 2.30) and maternal perception of a low
      influence on health (OR 0.51, CI 0.29 to 0.89) were also significantly associated
      with maternal encouragement. For boys, this was true of mothers self-efficacy to
      influence their children's physical activity (OR 0.58, CI 0.40 to 0.85).
      CONCLUSION: Different factors are associated with mothers encouraging boys and
      girls to control their weight. Identifying correlates and underlying processes of
      maternal encouragement can inform preventive measures targeting weight and eating
      related problems in children.

PMID- 24885350
TI  - Identification of genes regulating migration and invasion using a new model of
      metastatic prostate cancer.
AB  - BACKGROUND: Understanding the complex, multistep process of metastasis remains a
      major challenge in cancer research. Metastasis models can reveal insights in
      tumor development and progression and provide tools to test new intervention
      strategies. METHODS: To develop a new cancer metastasis model, we used DU145
      human prostate cancer cells and performed repeated rounds of orthotopic prostate
      injection and selection of subsequent lymph node metastases. Tumor growth,
      metastasis, cell migration and invasion were analyzed. Microarray analysis was
      used to identify cell migration- and cancer-related genes correlating with
      metastasis. Selected genes were silenced using siRNA, and their roles in cell
      migration and invasion were determined in transwell migration and Matrigel
      invasion assays. RESULTS: Our in vivo cycling strategy created cell lines with
      dramatically increased tumorigenesis and increased ability to colonize lymph
      nodes (DU145LN1-LN4). Prostate tumor xenografts displayed increased
      vascularization, enlarged podoplanin-positive lymphatic vessels and invasive
      margins. Microarray analysis revealed gene expression profiles that correlated
      with metastatic potential. Using gene network analysis we selected 3
      significantly upregulated cell movement and cancer related genes for further
      analysis: EPCAM (epithelial cell adhesion molecule), ITGB4 (integrin beta4) and
      PLAU (urokinase-type plasminogen activator (uPA)). These genes all showed
      increased protein expression in the more metastatic DU145-LN4 cells compared to
      the parental DU145. SiRNA knockdown of EpCAM, integrin-beta4 or uPA all
      significantly reduced cell migration in DU145-LN4 cells. In contrast, only uPA
      siRNA inhibited cell invasion into Matrigel. This role of uPA in cell invasion
      was confirmed using the uPA inhibitors, amiloride and UK122. CONCLUSIONS: Our
      approach has identified genes required for the migration and invasion of
      metastatic tumor cells, and we propose that our new in vivo model system will be
      a powerful tool to interrogate the metastatic cascade in prostate cancer.

PMID- 24885352
TI  - Biofertilizers function as key player in sustainable agriculture by improving
      soil fertility, plant tolerance and crop productivity.
AB  - Current soil management strategies are mainly dependent on inorganic chemical
      based fertilizers, which caused a serious threat to human health and environment.
      The exploitation of beneficial microbes as a biofertilizer has become paramount
      importance in agriculture sector for their potential role in food safety and
      sustainable crop production. The eco-friendly approaches inspire a wide range of
      application of plant growth promoting rhizobacteria (PGPRs), endo- and
      ectomycorrhizal fungi, cyanobacteria and many other useful microscopic organisms
      led to improved nutrient uptake, plant growth and plant tolerance to abiotic and
      biotic stress. The present review highlighted biofertilizers mediated crops
      functional traits such as plant growth and productivity, nutrient profile, plant
      defense and protection with special emphasis to its function to trigger various
      growth- and defense-related genes in signaling network of cellular pathways to
      cause cellular response and thereby crop improvement. The knowledge gained from
      the literature appraised herein will help us to understand the physiological
      bases of biofertlizers towards sustainable agriculture in reducing problems
      associated with the use of chemicals fertilizers. 

PMID- 24885353
TI  - Pediatricians' oral health recommendations for 0- to 3-year-old children: results
      of a survey in Thuringia, Germany.
AB  - BACKGROUND: German societies of pediatricians and dentists disagree about oral
      health-related preventive recommendations (use of fluoride supplements, fluoride
      containing toothpaste) for children aged 0-3 years. After failure to reach a
      consensus, there is no study that has evaluated the guidelines that pediatricians
      use in daily practice. METHODS: A standardized questionnaire was sent to all 167
      practicing pediatricians in the state of Thuringia, Germany, to assess the
      current oral health-related preventive recommendations. Data were analyzed using
      descriptive statistics. RESULTS: The response rate was 52.0%. More than 9.0% of
      the pediatricians advise parents with regard to diet, use of baby bottles, oral
      hygiene and dental visits. The majority of pediatricians recommend to start tooth
      brushing after the 1st birthday and recommend the use of toothpaste and a 1st
      dental visit after the 2nd birthday (78.0%). Additionally, 23.3% (n = 20) of
      pediatricians prescribe solely vitamin D, and 20.9% (n = 18) prescribe vitamin D
      combined with fluoride. Fluoride supplements are given as required by 37.2% (n =
      32) of pediatricians, primarily between the 1st and 6th birthdays. The guidelines
      of the Pediatric Society were used by 1.2% of the pediatricians, the guidelines
      of the dentists were used by 5.8%, and a mix of both was used by 93.0%. The
      simultaneous use of fluoride supplements and fluoride toothpaste in the first
      three years was recommended by 45.9% of the pediatricians. CONCLUSIONS:
      Pediatricians' oral health recommendations are based on a mix of the guidelines
      from the German societies of pediatricians and dentists and led to no use or
      possible overdose of fluoride. Against the background of early childhood caries
      and dental fluorosis, there is a need for uniform guidelines.

PMID- 24885354
TI  - Dexamethasone for the prevention of a pain flare after palliative radiotherapy
      for painful bone metastases: a multicenter double-blind placebo-controlled
      randomized trial.
AB  - BACKGROUND: Radiotherapy has a good effect in palliation of painful bone
      metastases, with a pain response rate of more than 60%. However, shortly after
      treatment, in approximately 40% of patients a temporary pain flare occurs, which
      is defined as a two-point increase of the worst pain score on an 11-point rating
      scale compared to baseline, without a decrease in analgesic intake, or a 25%
      increase in analgesic intake without a decrease in worst pain score, compared to
      baseline. A pain flare has a negative impact on daily functioning and mood of
      patients. It is thought to be caused by periostial edema after radiotherapy.
      Dexamethasone might diminish this edema and thereby reduce the incidence of pain
      flare. Two non-randomized studies suggest that dexamethasone reduces the
      incidence of a pain flare by 50%. The aim of this trial is to study the
      effectiveness of dexamethasone to prevent a pain flare after palliative
      radiotherapy for painful bone metastases and to determine the optimal dose
      schedule. METHODS AND DESIGN: This study is a three-armed, double-blind, placebo
      controlled multicenter trial. We aim to include 411 patients with uncomplicated
      painful bone metastases from any type of primary solid tumor who receive short
      schedule radiotherapy (all conventional treatment schedules from one to six
      fractions). Arm 1 consists of daily placebo for four days, arm 2 starts with 8 mg
      dexamethasone before the (first) radiotherapy and three days placebo thereafter.
      Arm 3 consists of four days 8 mg dexamethasone. The primary endpoint is the
      occurrence of a pain flare. Secondary endpoints are pain, quality of life and
      side-effects of dexamethasone versus placebo. Patients complete a questionnaire
      (Brief Pain Inventory with two added questions about side-effects of medication,
      the EORTC QLQ-C15-PAL and QLQ-BM22 for quality of life) at baseline, daily for
      two weeks and lastly at four weeks. DISCUSSION: This study will show whether
      dexamethasone is effective in preventing a pain flare after palliative
      radiotherapy for painful bone metastases and, if so, to determine the optimal
      dose. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov:
      NCT01669499.

PMID- 24885355
TI  - The current status of knowledge of herbal medicine and medicinal plants in Fiche,
      Ethiopia.
AB  - BACKGROUND: A majority of Ethiopians rely on traditional medicine as their
      primary form of health care, yet they are in danger of losing both their
      knowledge and the plants they have used as medicines for millennia. This study,
      conducted in the rural town of Fiche in Ethiopia, was undertaken with the support
      of Southern Cross University (SCU) Australia, Addis Ababa University (AAU)
      Ethiopia, and the Ethiopian Institute of Biodiversity (EIB), Ethiopia. The aim of
      this study, which included an ethnobotanical survey, was to explore the
      maintenance of tradition in the passing on of knowledge, the current level of
      knowledge about medicinal herbs and whether there is awareness and concern about
      the potential loss of both herbal knowledge and access to traditional medicinal
      plants. METHODS: This study was conducted using an oral history framework with
      focus groups, unstructured and semi-structured interviews, field-walk/discussion
      sessions, and a market survey. Fifteen people were selected via purposeful and
      snowball sampling. Analysis was undertaken using a grounded theory methodology.
      RESULTS: Fourteen lay community members and one professional herbalist provided
      information about 73 medicinal plants used locally. An ethnobotanical survey was
      performed and voucher specimens of 53 of the plants, representing 33 families,
      were collected and deposited at the EIB Herbarium. The community members are
      knowledgeable about recognition of medicinal plants and their usage to treat
      common ailments, and they continue to use herbs to treat sickness as they have in
      the past. A willingness to share knowledge was demonstrated by both the
      professional herbalist and lay informants. Participants are aware of the threat
      to the continued existence of the plants and the knowledge about their use, and
      showed willingness to take steps to address the situation. CONCLUSION: There is
      urgent need to document the valuable knowledge of medicinal herbs in Ethiopia.
      Ethnobotanical studies are imperative, and concomitant sustainable programmes
      that support the sustainability of herbal medicine traditions may be considered
      as a way to collect and disseminate information thereby supporting communities in
      their efforts to maintain their heritage. This study contributes to the
      documentation of the status of current traditional herbal knowledge in Ethiopia.

PMID- 24885356
TI  - The role of beliefs on learning about homosexuality in a college course.
AB  - The present research investigated how personal beliefs about homosexuality
      influence learning in a college course. We tested students in introductory
      psychology over material on the science of homosexuality by Simon LeVay (2010).
      All students reported information about their typical academic habits and the
      extent to which homosexuality was consistent with their beliefs and values. The
      results showed that students' personal beliefs were related to academic behaviors
      (e.g., reading assignments, skipping class) and retention of the course material.
      The results also showed that students' recall of course material six weeks later
      was predicted by the extent to which they reported studying information that is
      inconsistent with their beliefs for an exam and then forgetting it. Students who
      reported the material to be inconsistent with their beliefs engaged in selective
      forgetting of the material on homosexuality. The results provide evidence that
      personal beliefs can reduce the retention of belief-inconsistent information in a
      college course. 

PMID- 24885357
TI  - Comparison of diffusion-weighted imaging and contrast-enhanced T1-weighted
      imaging on a single baseline MRI for demonstrating dissemination in time in
      multiple sclerosis.
AB  - BACKGROUND: The 2010 Revisions to the McDonald Criteria have established that
      dissemination in time (DIT) of multiple sclerosis (MS) can be demonstrated by
      simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing
      lesions on a single magnetic resonance imaging (MRI). However, gadolinium-based
      contrast agents (GBCAs) have contraindications. Diffusion-weighted imaging (DWI)
      can detect diffusion alterations in active inflammatory lesions. The purpose of
      this study was to investigate if DWI can be an alternative to contrast-enhanced
      T1-weighted imaging (CE T1WI) for demonstrating DIT in MS. METHODS: We selected
      patients with clinically definite MS and evaluated their baseline brain MRI.
      Asymptomatic lesions were identified as either hyperintense or nonhyperintense on
      DWI and enhancing or nonenhancing on CE T1WI. Fisher's exact test was performed
      to determine whether the hyperintensity on DWI was related to the enhancement on
      CE T1WI (P < 0.05). The sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and accuracy of the DWI to predict lesion
      enhancement were calculated. RESULTS: Twenty-two patients with 384 demyelinating
      lesions that were hyperintense on T2-weighted imaging and more than 3 mm in size
      were recruited. The diffusion hyperintensity and lesion enhancement were
      significantly correlated (P <0.001). The sensitivity, specificity, PPV, NPV and
      accuracy were 100%, 67.9%, 32.3%, 100% and 72.1%, respectively. CONCLUSIONS: A
      hyperintense DWI finding does not necessarily overlap with contrast enhancement.
      There are many false positives, possibly representing other stages of lesion
      development. Although DWI may not replace CE T1WI imaging to demonstrate DIT due
      to the low PPV, it may serve as a screening MRI sequence where the use of GBCAs
      is a concern.

PMID- 24885358
TI  - Psychometric evaluation of the Korean version of the Diabetes Symptom Checklist
      Revised (DSC-R) for patients with type 2 diabetes.
AB  - BACKGROUND: This study was to elucidate the psychometric properties of the Korean
      version of the Diabetes Symptom Checklist-Revised (K-DSC-R), which is a patient
      reported outcome measure of diabetes symptom burden. METHODS: A sample of 432
      Korean patients with diabetes was recruited from university hospitals. The data
      were analyzed using exploratory factor analysis (EFA), confirmatory factor
      analysis (CFA), multitrait/multi-item correlation, Pearson's correlation, t-test,
      ANOVA, and Cronbach's alpha for construct, item-convergent/discriminant,
      concurrent, and known-groups validity, and internal consistency reliability.
      RESULTS: EFA extracted a total of 29 items clustered into 7 subscales from the K
      DSC-R. The construct of the seven-subscales was supported by CFA. The scaling
      success rates of item-convergent validity were 100% for all subscales, and those
      of item-discriminant validity ranged from 83.3% to 100%. Patients in more
      depressed groups and in the HbA1c-uncontrolled group had higher K-DSC-R scores,
      satisfying the known-groups validity. The subscales of the K-DSC-R were
      moderately correlated with health-related quality of life, indicative of the
      established concurrent validity. The Cronbach's alpha of the K-DSC-R was 0.92.
      CONCLUSIONS: The psychometric properties of the K-DSC-R have been established. It
      is thus appropriate for use with respect to reliability and validity in practice
      and clinical trials for Korean patients with type 2 diabetes.

PMID- 24885359
TI  - Fermentation performance and physiology of two strains of Saccharomyces
      cerevisiae during growth in high gravity spruce hydrolysate and spent sulphite
      liquor.
AB  - BACKGROUND: Lignocellulosic materials are a diverse group of substrates that are
      generally scarce in nutrients, which compromises the tolerance and fermentation
      performance of the fermenting organism. The problem is exacerbated by harsh pre
      treatment, which introduces sugars and substances inhibitory to yeast metabolism.
      This study compares the fermentation behaviours of two yeast strains using
      different types of lignocellulosic substrates; high gravity dilute acid spruce
      hydrolysate (SH) and spent sulphite liquor (SSL), in the absence and presence of
      yeast extract. To this end, the fermentation performance, energy status and
      fermentation capacity of the strains were measured under different growth
      conditions. RESULTS: Nutrient supplementation with yeast extract increased sugar
      uptake, cell growth and ethanol production in all tested fermentation conditions,
      but had little or no effect on the energy status, irrespective of media. Nutrient
      supplemented medium enhanced the fermentation capacity of harvested cells,
      indicating that cell viability and reusability was increased by nutrient
      addition. CONCLUSIONS: Although both substrates belong to the lignocellulosic
      spruce hydrolysates, their differences offer specific challenges and the overall
      yields and productivities largely depend on choice of fermenting strain.

PMID- 24885360
TI  - Compliance potential mapping: a tool to assess potential contributions of walking
      towards physical activity guidelines.
AB  - BACKGROUND: Walking for transport is increasingly considered an important
      component for meeting physical activity guidelines. This is true for individuals
      of all ages, and particularly important for seniors, for whom other physical
      activities may not be recommended. In order to evaluate the potential
      contributions of walking to physical activity, in this paper the concept of
      Compliance Potential Mapping is introduced. The concept is illustrated using
      seniors as a case study. METHODS: Based on estimates of walking trip distance and
      frequency, estimates of expected total daily walking distance are obtained. These
      estimates are converted to weekly walking minutes, which are in turn compared to
      recommended physical activity guidelines for seniors. Once estimates of travel
      behavior are available, the approach is straightforward and based on relatively
      simple map algebra operations. RESULTS: Compliance Potential Mapping as a tool to
      assess the potential contributions of walking towards physical activity is
      demonstrated using data from Montreal's 2008 travel survey. The results indicate
      that the central parts of Montreal Island display higher potential for compliance
      with physical activity guidelines, but with variations according to age, income,
      occupation, possession of driver's license and vehicle, and neighborhood and
      accessibility parameters. CONCLUSIONS: Compliance Potential Maps offer valuable
      information for public health and transportation planning and policy analysis.

PMID- 24885361
TI  - The impact of omega-3 polyunsaturated fatty acid supplementation on the incidence
      of cardiovascular events and complications in peripheral arterial disease: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Individuals with peripheral arterial disease are at higher risk for
      cardiovascular events than the general population. While supplementation with
      omega-3 polyunsaturated fatty acids (PUFA) has been shown to improve vascular
      function, it remains unclear if supplementation decreases serious clinical
      outcomes. We conducted a systematic review and meta-analysis to determine whether
      omega-3 PUFA supplementation reduces the incidence of cardiovascular events and
      complications in adults with peripheral arterial disease. METHODS: We searched
      five electronic databases (MEDLINE, EMBASE, CENTRAL, Scopus and the International
      Clinical Trials Registry Platform) from inception to 6 December 2013 to identify
      randomized trials of omega-3 PUFA supplementation (from fish or plant oils) that
      lasted >=12 weeks in adults with peripheral arterial disease. No language filters
      were applied. Data on trial design, population characteristics, and health
      outcomes were extracted. The primary outcome was major adverse cardiac events;
      secondary outcomes included myocardial infarction, cardiovascular death, stroke,
      angina, amputation, revascularization procedures, maximum and pain-free walking
      distance, adverse effects of the intervention, and quality of life. Trial quality
      was assessed using the Cochrane Risk of Bias tool. RESULTS: Of 741 citations
      reviewed, we included five trials enrolling 396 individuals. All included trials
      were of unclear or high risk of bias. There was no evidence of a protective
      association of omega-3 PUFA supplementation against major adverse cardiac events
      (pooled risk ratio 0.73, 95% CI 0.22 to 2.41, I2 75%, 2 trials, 288 individuals)
      or other serious clinical outcomes. Adverse events and compliance were poorly
      reported. CONCLUSIONS: Our results showed that insufficient evidence exists to
      suggest a beneficial effect of omega-3 PUFA supplementation in adults with
      peripheral arterial disease with regard to cardiovascular events and other
      serious clinical outcomes.

PMID- 24885362
TI  - De Novo modeling of Envelope 2 protein of HCV isolated from Pakistani patient and
      epitopes prediction for vaccine development.
AB  - Hepatitis C virus (HCV) is a universal health issue and a significant risk factor
      leading to hepatocellular carcinoma. HCV has infected approximately 170 million
      individuals worldwide. It is a member of Flaviviridae with positive sense RNA
      genome. In the absence of any effective vaccine against HCV, pegylated interferon
      with ribavirin is the standard of treatment against HCV infection. In this study,
      sequence and structural analysis of envelope 2 (E2) protein was performed which
      was isolated from patients of HCV genotype 3a in Pakistan. Then, epitopes were
      predicted which were specific for both B-cells and T-cells. Later, conservancy of
      epitopes was checked with the HCV 3a and 1a sequences from different countries. A
      total of 6 conserved epitopes were found from extra-membranous regions of E2
      protein. Presence of conserved epitopes in E2 protein generates the possibility
      that these epitopes can be used to elicit the immune response against HCV. 

PMID- 24885363
TI  - Increased expression of stathmin and elongation factor 1alpha in precancerous
      nodules with telomere dysfunction in hepatitis B viral cirrhotic patients.
AB  - BACKGROUND: Telomere dysfunction is important in carcinogenesis, and recently,
      stathmin and elongation factor 1alpha (EF1alpha) were reported to be up-regulated
      in telomere dysfunctional mice. METHODS: In the present study, the expression
      levels of stathmin and EF1alpha in relation to telomere length, telomere
      dysfunction-induced foci (TIF), gamma-H2AX, and p21WAF1/CIP1 expression were
      assessed in specimens of hepatitis B virus (HBV)-related multistep
      hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade
      dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas
      (HCC). Five normal liver specimens were used as controls. TIF were analyzed by
      telomere fluorescent in situ hybridization (FISH) combined with immunostaining,
      while the protein expressions of stathmin, EF1alpha, gamma-H2AX, and p21WAF1/CIP1
      were detected by immunohistochemistry. RESULT: The expressions of stathmin and
      EF1alpha gradually increased as multistep hepatocarcinogenesis progressed,
      showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade
      DNs than normal liver and liver cirrhosis, whereas EF1alpha mRNA expression did
      not show such a difference. The protein expressions of stathmin and EF1alpha were
      found in DNs of precancerous lesions, whereas they were absent or present at very
      low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher
      in high-grade DNs and low-grade DNs than in normal liver (all, P<0.05). EF1alpha
      histoscores were higher in high-grade DNs than in normal liver and liver
      cirrhosis (all, P<0.05). Stathmin mRNA levels and histoscores, as well as
      EF1alpha histoscores (but not mRNA levels), were positively correlated with
      telomere shortening and gamma-H2AX labeling index (all, P<0.05). EF1alpha
      histoscores were also positively correlated with TIF (P<0.001). Significantly
      greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade
      DNs, and HCC, compared to liver cirrhosis (all, P<0.05). p21WAF1/CIP1 labeling
      index was inversely correlated with TIF, stathmin mRNA level, and EF1alpha
      histoscore (all, P<0.05). CONCLUSION: Stathmin and EF1alpha are suggested to be
      closely related to telomere dysfunction, DNA damage, and inactivation of
      p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly,
      assessment of stathmin and EF1alpha levels as a reflection of telomere
      dysfunction may be helpful in evaluating the biological characteristics of
      precancerous hepatic nodules in hepatitis B viral cirrhotic patients.

PMID- 24885364
TI  - Anti-salivary gland protein 1 antibodies in two patients with Sjogren's syndrome:
      two case reports.
AB  - INTRODUCTION: Current diagnostic criteria for Sjogren's syndrome developed by the
      American College of Rheumatology include the presence of antinuclear antibodies,
      rheumatoid factor, anti-Ro or anti-La autoantibodies. The purpose of this report
      is to describe two patients with biopsy-proven Sjogren's syndrome lacking these
      autoantibodies but identified by antibodies to salivary gland protein 1.
      Diagnosis was delayed until salivary gland tumors developed in these patients
      because of the lack of the classic autoantibodies. This report emphasizes the
      existence of patients with primary Sjogren's syndrome who lack autoantibodies
      anti-Ro or anti-La and may therefore be misdiagnosed. Antibodies to salivary
      gland protein 1 identify some of these patients. CASE PRESENTATION: Two patients
      are described and were seen in the autoimmune disease clinics of the State
      University of New York (SUNY) at the Buffalo School of Medicine. In both
      patients, chronic dry mouth and dry eye had been dismissed as idiopathic because
      test results for autoantibodies anti-Ro and anti-La were negative. Both patients
      had swelling of major salivary glands that prompted biopsies. Biopsies of major
      salivary glands from both cases demonstrated salivary gland tumors and existence
      of inflammation consistent with Sjogren's syndrome. Serologic testing revealed
      antibodies to salivary gland protein 1. CONCLUSIONS: Patients presenting with
      classic clinical symptoms of dry mouth and eyes do not always show the current
      serologic markers of Sjogren's syndrome, anti-Ro and anti-La. In these cases,
      investigation for antibodies to salivary gland protein 1 is of importance to make
      the diagnosis of Sjogren's syndrome. Early diagnosis of Sjogren's syndrome is
      necessary for improved management as well as for vigilance regarding potential
      complications, such as salivary gland tumors as were seen in the described cases.

PMID- 24885365
TI  - Increased macular choroidal blood flow velocity and decreased choroidal thickness
      with regression of punctate inner choroidopathy.
AB  - BACKGROUND: Changes in choroidal circulation hemodynamics during the course of
      punctate inner choroidopathy (PIC) remain unknown. The aim of this study was to
      quantitatively evaluate changes in choroidal blood flow velocity by using laser
      speckle flowgraphy (LSFG) in patients with PIC. CASE PRESENTATION: This PIC
      patient was initially treated with systemic corticosteroids for 4 months. LSFG
      measurements were taken 10 consecutive times before treatment and at 1, 3, 12, 20
      and 23 months after the initiation of therapy. The mean blur rate (MBR), a
      quantitative index of relative blood flow velocity, was calculated using LSFG in
      three regions: Circles 1, 2 and 3 were set at the fovea, a lesion site, and an
      area of normal-appearing retina, respectively.The PIC lesions scarred after
      treatment along with improvements in visual function and outer retinal
      morphology. When the changing rate of macular flow over the 12-month follow-up
      period was compared with the MBR before treatment (100%), an increase of 16-37%,
      24-49% and 15-18% was detected in Circles 1, 2 and 3, respectively. At the time
      of PIC recurrence after 20 months, the MBR decreased temporarily but subsequently
      increased after retreatment with systemic corticosteroids. This trend was
      accompanied by a decrease in choroidal thickness at the lesion site after
      retreatment. CONCLUSIONS: Macular choroidal blood flow velocity increased and
      choroidal thickness decreased concurrently with regression of PIC. The present
      findings suggest that inflammation-related impairments in choroidal circulation
      may relate to the pathogenesis of PIC, extending over a wider area in the
      posterior pole than the PIC lesions per se.

PMID- 24885366
TI  - Life-threatening rupture of an external iliac artery pseudoaneurysm caused by
      necrotizing fasciitis following laparoscopic radical cystectomy: a case report.
AB  - BACKGROUND: Pseudoaneurysms are caused by trauma, tumors, infections, vasculitis,
      atherosclerosis and iatrogenic complications. In this paper, we report about a
      patient with rupture of an external iliac artery pseudoaneurysm, which lead to
      hemorrhagic shock, after undergoing laparoscopic radical cystectomy and extended
      pelvic lymphadenectomy. CASE PRESENTATION: The patient was a 68-year-old Japanese
      male diagnosed with invasive bladder cancer. Laparoscopic radical cystectomy and
      extended pelvic lymphadenectomy were performed. On postoperative day 12, he
      developed a high fever and an acute inflammatory response with redness and
      swelling in the right inguinal region. He was diagnosed with necrotizing
      fasciitis and underwent debridement. On postoperative day 42, a sudden hemorrhage
      developed from the open wound in the right inguinal region. He was diagnosed with
      external iliac artery pseudoaneurysm rupture by computed tomography. CONCLUSION:
      These complications occur extremely rarely after cystectomy with pelvic
      lymphadenectomy. There are no reports to date on these complications following
      laparoscopic cystectomy with pelvic lymphadenectomy.

PMID- 24885367
TI  - Mouse CCDC79 (TERB1) is a meiosis-specific telomere associated protein.
AB  - BACKGROUND: Telomeres have crucial meiosis-specific roles in the orderly
      reduction of chromosome numbers and in ensuring the integrity of the genome
      during meiosis. One such role is the attachment of telomeres to trans-nuclear
      envelope protein complexes that connect telomeres to motor proteins in the
      cytoplasm. These trans-nuclear envelope connections between telomeres and
      cytoplasmic motor proteins permit the active movement of telomeres and
      chromosomes during the first meiotic prophase. Movements of chromosomes/telomeres
      facilitate the meiotic recombination process, and allow high fidelity pairing of
      homologous chromosomes. Pairing of homologous chromosomes is a prerequisite for
      their correct segregation during the first meiotic division. Although inner
      nuclear envelope proteins, such as SUN1 and potentially SUN2, are known to bind
      and recruit meiotic telomeres, these proteins are not meiosis-specific, therefore
      cannot solely account for telomere-nuclear envelope attachment and/or for other
      meiosis-specific characteristics of telomeres in mammals. RESULTS: We identify
      CCDC79, alternatively named TERB1, as a meiosis-specific protein that localizes
      to telomeres from leptotene to diplotene stages of the first meiotic prophase.
      CCDC79 and SUN1 associate with telomeres almost concurrently at the onset of
      prophase, indicating a possible role for CCDC79 in telomere-nuclear envelope
      interactions and/or telomere movements. Consistent with this scenario, CCDC79 is
      missing from most telomeres that fail to connect to SUN1 protein in spermatocytes
      lacking the meiosis-specific cohesin SMC1B. SMC1B-deficient spermatocytes display
      both reduced efficiency in telomere-nuclear envelope attachment and reduced
      stability of telomeres specifically during meiotic prophase. Importantly, CCDC79
      associates with telomeres in SUN1-deficient spermatocytes, which strongly
      indicates that localization of CCDC79 to telomeres does not require telomere
      nuclear envelope attachment. CONCLUSION: CCDC79 is a meiosis-specific telomere
      associated protein. Based on our findings we propose that CCDC79 plays a role in
      meiosis-specific telomere functions. In particular, we favour the possibility
      that CCDC79 is involved in telomere-nuclear envelope attachment and/or the
      stabilization of meiotic telomeres. These conclusions are consistent with the
      findings of an independently initiated study that analysed CCDC79/TERB1
      functions.

PMID- 24885368
TI  - Demethylation of the miR-146a promoter by 5-Aza-2'-deoxycytidine correlates with
      delayed progression of castration-resistant prostate cancer.
AB  - BACKGROUND: Androgen deprivation therapy is the primary strategy for the
      treatment of advanced prostate cancer; however, after an initial regression, most
      patients will inevitably develop a fatal androgen-independent tumor. Therefore,
      understanding the mechanisms of the transition to androgen independence prostate
      cancer is critical to identify new ways to treat older patients who are
      ineligible for conventional chemotherapy. METHODS: The effects of 5-Aza-2'
      deoxycytidine (5-Aza-CdR) on the viability and the apoptosis of the androgen
      dependent (LNCaP) and androgen-independent (PC3) cell lines were examined by MTS
      assay and western blot analysis for the activation of caspase-3. The subcutaneous
      LNCaP xenografts were established in a nude mice model. MiR-146a and DNMTs
      expressions were analyzed by qRT-PCR and DNA methylation rates of LINE-1 were
      measured by COBRA-IRS to determine the global DNA methylation levels. The
      methylation levels of miR-146a promoter region in the different groups were
      quantified by the bisulfite sequencing PCR (BSP) assay. RESULTS: We validated
      that 5-Aza-CdR induced cell death and increased miR-146a expression in both LNCaP
      and PC3 cells. Notably, the expression of miR-146a in LNCaP cells was much higher
      than in PC3 cells. MiR-146a inhibitor was shown to suppress apoptosis in 5-Aza
      CdR-treated cells. In a castrate mouse LNCaP xenograft model, 5-Aza-CdR
      significantly suppressed the tumors growth and also inhibited prostate cancer
      progression. Meanwhile, miR-146a expression was significantly enhanced in the
      tumor xenografts of 5-Aza-CdR-treated mice and the androgen-dependent but not the
      androgen-independent stage of castrated mice. In particular, the expression of
      miR-146a was significantly augmented in both stages of the combined treatment
      (castration and 5-Aza-CdR). Additionally, the methylation percentage of the two
      CpG sites (-444 bp and -433 bp), which were around the NF-kappaB binding site at
      miR-146a promoter, showed the lowest methylation levels among all CpG sites in
      the combined treatment tumors of both stages. CONCLUSION: Up-regulating miR-146a
      expression via the hypomethylation of the miR-146a promoter by 5-Aza-CdR was
      correlated with delayed progression of castration-resistant prostate cancers.
      Moreover, site-specific DNA methylation may play an important role in miR-146a
      expression in androgen-dependent prostate cancer progression to androgen
      independent prostate cancer and therefore provides a potentially useful biomarker
      for assessing drug efficacy in prostate cancer.

PMID- 24885369
TI  - A symmetry model for genetic coding via a wallpaper group composed of the
      traditional four bases and an imaginary base E: towards category theory-like
      systematization of molecular/genetic biology.
AB  - BACKGROUND: Previously, we suggested prototypal models that describe some
      clinical states based on group postulates. Here, we demonstrate a group/category
      theory-like model for molecular/genetic biology as an alternative application of
      our previous model. Specifically, we focus on deoxyribonucleic acid (DNA) base
      sequences. RESULTS: We construct a wallpaper pattern based on a five-letter
      cruciform motif with letters C, A, T, G, and E. Whereas the first four letters
      represent the standard DNA bases, the fifth is introduced for ease in formulating
      group operations that reproduce insertions and deletions of DNA base sequences. A
      basic group Z5 = {r, u, d, l, n} of operations is defined for the wallpaper
      pattern, with which a sequence of points can be generated corresponding to
      changes of a base in a DNA sequence by following the orbit of a point of the
      pattern under operations in group Z5. Other manipulations of DNA sequence can be
      treated using a vector-like notation 'Dj' corresponding to a DNA sequence but
      based on the five-letter base set; also, 'Dj's are expressed graphically.
      Insertions and deletions of a series of letters 'E' are admitted to assist in
      describing DNA recombination. Likewise, a vector-like notation Rj can be
      constructed for sequences of ribonucleic acid (RNA). The wallpaper group B =
      {Z5*infinity, ?} (an infinity-fold Cartesian product of Z5) acts on Dj (or Rj)
      yielding changes to Dj (or Rj) denoted by 'Dj?B(j->k) = Dk' (or 'Rj?B(j->k) =
      Rk'). Based on the operations of this group, two types of groups-a modulo 5
      linear group and a rotational group over the Gaussian plane, acting on the five
      bases-are linked as parts of the wallpaper group for broader applications. As a
      result, changes, insertions/deletions and DNA (RNA) recombination (partial/total
      conversion) are described. As an exploratory study, a notation for the canonical
      "central dogma" via a category theory-like way is presented for future
      developments. CONCLUSIONS: Despite the large incompleteness of our methodology,
      there is fertile ground to consider a symmetry model for genetic coding based on
      our specific wallpaper group. A more integrated formulation containing "central
      dogma" for future molecular/genetic biology remains to be explored.

PMID- 24885370
TI  - Low prevalence of IgA anti-transglutaminase 1, 2, and 3 autoantibodies in
      children with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin
      disease presenting with a relapsing clinical pattern similar to chronic
      autoimmune disease. Several human transglutaminases have been defined and
      keratinocyte transglutaminase (TG1) and epidermal transglutaminase (TG3)
      expressed in the epidermis are associated with epidermal barrier dysfunction.
      Since impairments to the epidermal barrier represent an important factor in AD,
      we hypothesized that IgA autoantibodies specific for TG1 (IgA-anti-TG1) and TG3
      (IgA-anti-TG3) may affect AD development during childhood. METHODS: Active AD
      patients (n = 304), 28 patients with biopsy-confirmed coeliac disease (CD), 5
      patients with active AD and CD, and 55 control patients without CD and skin
      diseases were enrolled into the study. IgA-anti-TG1 and IgA-anti-TG3 reactivity
      was determined using an enzyme-linked immunosorbent assay. IgA-anti-TG2 were
      defined using a fluoroenzyme immunoassay. RESULTS: IgA-anti-TG1 antibodies were
      found in 2% and IgA-anti-TG3 antibodies in 3% of patients with active AD. Two out
      of the 5 patients with AD and concomitant CD had IgA-anti-TG1 and IgA-anti-TG2
      antibodies. In CD patients, 36% of individuals presented with elevated IgA-anti
      TG1 antibodies and 18% presented with elevated IgA-anti-TG3 antibodies and all CD
      patients presented with IgA-anti-TG2 antibodies (significantly different from AD
      patients and controls, p < 0.05). In CD patients, IgA-anti-TG1 and/or IgA-anti
      TG3 seropositivity tended to appear concurrently, whereas only one patient with
      AD had both types of autoantibodies. CONCLUSIONS: IgA-anti-TG1 and IgA-anti-TG3
      seropositivity was rare in active AD but frequent in CD patients. The level of
      circulating antibodies related to skin lesions could be studied by determining
      the levels of IgA-anti-TG1 and IgA-anti-TG3 in skin biopsies of AD patients.

PMID- 24885372
TI  - Asymmetric supported lipid bilayer formation via methyl-beta-cyclodextrin
      mediated lipid exchange: influence of asymmetry on lipid dynamics and phase
      behavior.
AB  - Supported lipid bilayers (SLBs) are broadly used as minimal membrane models and
      commonly produced by vesicle fusion (VF) on solid supports. Despite its
      advantages, VF does not allow the controlled formation of bilayers that mimic the
      leaflet asymmetry in lipid composition normally found in biological systems. Here
      we present a simple, quick, and versatile method to produce SLBs with a desired
      asymmetric lipid composition which is stable for ca. 4 h. We apply methyl-beta
      cyclodextrin mediated lipid exchange to SLBs formed by VF to enrich the upper
      leaflet of the bilayer with sphingomyelin. The bilayer asymmetry is assessed by
      fluorescence correlation spectroscopy, measuring the lipid mobility separately in
      each leaflet. To check the compatibility of the method with the most common
      protein reconstitution approaches, we report the production of asymmetric SLBs
      (aSLBs) in the presence of a glycosylphosphatidylinositol-anchored protein,
      reconstituted in the bilayer both, via direct protein insertion, and via
      proteoliposomes fusion. We finally apply aSLBs to study phase separation and
      transbilayer lipid movement of raft-mimicking lipid mixtures. The observed
      differences in terms of phase separation in symmetric and asymmetric SLBs with
      the same overall lipid composition provide further experimental evidence that the
      transversal lipid distribution affects the overall lipid miscibility and allow to
      temporally investigate leaflet mixing. 

PMID- 24885371
TI  - Investigating the effects of Pleistocene events on genetic divergence within
      Richardsonius balteatus, a widely distributed western North American minnow.
AB  - BACKGROUND: Biogeographers seek to understand the influences of global climate
      shifts and geologic changes to the landscape on the ecology and evolution of
      organisms. Across both longer and shorter timeframes, the western North American
      landscape has experienced dynamic transformations related to various geologic
      processes and climatic oscillations, including events as recently as the Last
      Glacial Maximum (LGM; ~20 Ka) that have impacted the evolution of the North
      American biota. Redside shiner is a cyprinid species that is widely distributed
      throughout western North America. The species' native range includes several well
      documented Pleistocene refugia. Here we use mitochondrial DNA sequence data to
      assess phylogeography, and to test two biogeographic hypotheses regarding post
      glacial colonization by redside shiner: 1) Redside shiner entered the Bonneville
      Basin at the time of the Bonneville Flood (Late Pleistocene; 14.5 Ka), and 2)
      redside shiner colonized British Columbia post-glacially from a single refugium
      in the Upper Columbia River drainage. RESULTS: Genetic diversification in redside
      shiner began in the mid to late Pleistocene, but was not associated with LGM.
      Different clades of redside shiner were distributed in multiple glacial age
      refugia, and each clade retains a signature of population expansion, with clades
      having secondary contact in some areas. CONCLUSIONS: Divergence times between
      redside shiner populations in the Bonneville Basin and the Upper Snake/Columbia
      River drainage precedes the Bonneville Flood, thus it is unlikely that redside
      shiner invaded the Bonneville Basin during this flooding event. All but one
      British Columbia population of redside shiner are associated with the Upper
      Columbia River drainage with the lone exception being a population near the
      coast, suggesting that the province as a whole was colonized from multiple
      refugia, but the inland British Columbia redside shiner populations are
      affiliated with a refugium in the Upper Columbia River drainage.

PMID- 24885373
TI  - Role of platelet-derived growth factor/platelet-derived growth factor receptor
      axis in the trafficking of circulating fibrocytes in pulmonary fibrosis.
AB  - Circulating fibrocytes have been reported to migrate into the injured lungs, and
      contribute to fibrogenesis via CXCL12-CXCR4 axis. In contrast, we report that
      imatinib mesylate prevented bleomycin (BLM)-induced pulmonary fibrosis in mice by
      inhibiting platelet-derived growth factor receptor (PDGFR), even when it was
      administered only in the early phase. The goal of this study was to test the
      hypothesis that platelet-derived growth factor (PDGF) might directly contribute
      to the migration of fibrocytes to the injured lungs. PDGFR expression in
      fibrocytes was examined by flow cytometry and RT-PCR. The migration of fibrocytes
      was evaluated by using a chemotaxis assay for human fibrocytes isolated from
      peripheral blood. The numbers of fibrocytes triple-stained for CD45, collagen-1,
      and CXCR4 were also examined in lung digests of BLM-treated mice. PDGFR mRNA
      levels in fibrocytes isolated from patients with idiopathic pulmonary fibrosis
      were investigated by real-time PCR. Fibrocytes expressed both PDGFR-alpha and 
      beta, and migrated in response to PDGFs. PDGFR inhibitors (imatinib, PDGFR
      blocking antibodies) suppressed fibrocyte migration in vitro, and reduced the
      number of fibrocytes in the lungs of BLM-treated mice. PDGF-BB was a stronger
      chemoattractant than the other PDGFs in vitro, and anti-PDGFR-beta-blocking
      antibody decreased the numbers of fibrocytes in the lungs compared with anti
      PDGFR-alpha antibody in vivo. Marked expression of PDGFR-beta was observed in
      fibrocytes from patients with idiopathic pulmonary fibrosis compared with healthy
      subjects. These results suggest that PDGF directly functions as a strong
      chemoattractant for fibrocytes. In particular, the PDGF-BB-PDGFR-beta biological
      axis might play a critical role in fibrocyte migration into the fibrotic lungs. 

PMID- 24885376
TI  - Patient presentation and physician management of upper respiratory tract
      infections: a retrospective review of over 5 million primary clinic consultations
      in Hong Kong.
AB  - BACKGROUND: Upper respiratory tract infection (URTI) has a significant healthcare
      burden worldwide. Considerable resources are consumed through health care
      consultations and prescribed treatment, despite evidence for little or no effect
      on recovery. Patterns of consultations and care including use of symptomatic
      medications and antibiotics for upper respiratory tract infections are poorly
      described. METHODS: We performed a retrospective review of computerized clinical
      data on patients presenting to all public primary care clinics in Hong Kong with
      symptoms of respiratory tract infections. International Classification of Primary
      care (ICPC)codes used to identify patients included otitis media (H71),
      streptococcal pharyngitis (R72), acute URTI (R74), acute sinusitis (R75), acute
      tonsillitis (R76), acute laryngitis (R77), and influenza (R80). Sociodemographic
      variables such as gender, age, chronic illness status, attendance date, type and
      duration of drug prescribed were also collected. RESULTS: Of the 5,529,755
      primary care consultations for respiratory symptoms from 2005 to 2010, 98%
      resulted in a prescription. Prescription patterns of symptomatic medication were
      largely similar across the 5 years. In 2010 the mean number of drugs prescribed
      per consultation was 3.2, of which the commonly prescribed medication were
      sedating antihistamines (79.9%), analgesia (58.9%), throat lozenges (40.4%) and
      expectorant cough syrup (33.8%). During the study period, there was an overall
      decline in antibiotic prescription (8.1% to 5.1%). However, in consultations
      where the given diagnosis was otitis media (H71), streptococcal pharyngitis
      (R72), acute sinusitis (R75) or acute laryngitis (R76), over 90% resulted in
      antibiotic prescription. CONCLUSION: There was a decline in overall antibiotic
      prescription over the study period. However, the use of antibiotics was high in
      some conditions e.g. otitis media and acute laryngitis a. Multiple symptomatic
      medications were given for upper respiratory tract infections. Further research
      is needed to develop clinical and patients directed interventions to reduce the
      number of prescriptions of symptomatic medications and antibiotics that could
      reduce costs for health care services and iatrogenic risk to patients.

PMID- 24885374
TI  - Study protocol: The Whitehall II imaging sub-study.
AB  - BACKGROUND: The Whitehall II (WHII) study of British civil servants provides a
      unique source of longitudinal data to investigate key factors hypothesized to
      affect brain health and cognitive ageing. This paper introduces the multi-modal
      magnetic resonance imaging (MRI) protocol and cognitive assessment designed to
      investigate brain health in a random sample of 800 members of the WHII study.
      METHODS/DESIGN: A total of 6035 civil servants participated in the WHII Phase 11
      clinical examination in 2012-2013. A random sample of these participants was
      included in a sub-study comprising an MRI brain scan, a detailed clinical and
      cognitive assessment, and collection of blood and buccal mucosal samples for the
      characterisation of immune function and associated measures. Data collection for
      this sub-study started in 2012 and will be completed by 2016. The participants,
      for whom social and health records have been collected since 1985, were between
      60-85 years of age at the time the MRI study started. Here, we describe the pre
      specified clinical and cognitive assessment protocols, the state-of-the-art MRI
      sequences and latest pipelines for analyses of this sub-study. DISCUSSION: The
      integration of cutting-edge MRI techniques, clinical and cognitive tests in
      combination with retrospective data on social, behavioural and biological
      variables during the preceding 25 years from a well-established longitudinal
      epidemiological study (WHII cohort) will provide a unique opportunity to examine
      brain structure and function in relation to age-related diseases and the
      modifiable and non-modifiable factors affecting resilience against and
      vulnerability to adverse brain changes.

PMID- 24885377
TI  - Staged transthoracic approach to persistent atrial fibrillation (TOP-AF): study
      protocol for a randomized trial.
AB  - BACKGROUND: Persistent atrial fibrillation frequently shows multiple different
      electrophysiological mechanisms of induction. This heterogeneity causes a low
      success rate of single procedures of ablation and a high incidence of recurrence.
      Surgical ablation through bilateral thoracotomy demonstrates better results after
      a single procedure. Prospective observational studies in inhomogeneous
      populations without control groups report a remarkable 90% of success with hybrid
      or staged procedures of surgical ablation coupled with catheter ablation. In this
      trial, we will examine the hypothesis that a staged approach involving initial
      minimally invasive surgical ablation of persistent atrial fibrillation, followed
      by a second percutaneous procedure in case of recurrence, has a higher success
      rate than repeated percutaneous procedures. METHODS/DESIGN: This is a controlled
      (2:1) randomized trial comparing use of a percutaneous catheter with minimally
      invasive transthoracic surgical ablation of persistent atrial fibrillation. The
      inclusion and exclusion criteria, definitions, and treatment protocols are those
      reported by the 2012 Expert Consensus Statement on catheter and surgical ablation
      of atrial fibrillation. Patients will be randomized to either percutaneous
      catheter (n = 100) or surgical (n = 50) ablation as the first procedure. After 3
      months, they are re-evaluated, according to the same guidelines, and receive a
      second procedure if necessary. Crossover will be allowed and data analyzed on an
      "intention-to-treat" basis. Primary outcomes are the incidence of sinus rhythm at
      6 and 12 months and the proportions of patients requiring a second procedure.
      DISCUSSION: The use of a staged strategy combining surgical and percutaneous
      approaches might be more favorable in treatment of persistent atrial fibrillation
      than the controversial single percutaneous ablation. TRIAL REGISTRATION:
      ISRCTN08035058 Reg 06.20.2013.

PMID- 24885375
TI  - An Italian prospective multicenter survey on patients suspected of having non
      celiac gluten sensitivity.
AB  - BACKGROUND: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome
      with several unsettled issues despite the increasing awareness of its existence.
      We carried out a prospective survey on NCGS in Italian centers for the diagnosis
      of gluten-related disorders, with the aim of defining the clinical picture of
      this new syndrome and to establish roughly its prevalence compared with celiac
      disease. METHODS: From November 2012 to October 2013, 38 Italian centers (27
      adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy)
      participated in this prospective survey. A questionnaire was used in order to
      allow uniform and accurate collection of clinical, biochemical, and instrumental
      data. RESULTS: In total, 486 patients with suspected NCGS were identified in this
      1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years
      (range 3-81). The clinical picture was characterized by combined gastrointestinal
      (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain,
      gastroesophageal reflux, aphthous stomatitis) and systemic manifestations
      (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness,
      'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the
      large majority of patients, the time lapse between gluten ingestion and the
      appearance of symptoms varied from a few hours to 1 day. The most frequent
      associated disorders were irritable bowel syndrome (47%), food intolerance (35%)
      and IgE-mediated allergy (22%). An associated autoimmune disease was detected in
      14% of cases. Regarding family history, 18% of our patients had a relative with
      celiac disease, but no correlation was found between NCGS and positivity for HLA
      DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients
      tested. Only a proportion of patients underwent duodenal biopsy; for those that
      did, the biopsies showed normal intestinal mucosa (69%) or mild increase in
      intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD
      diagnoses, assessed in 28 of the participating centers, was 1.15 to 1.
      CONCLUSIONS: This prospective survey shows that NCGS has a strong correlation
      with female gender and adult age. Based on our results, the prevalence of NCGS
      seems to be only slightly higher than that of celiac disease.

PMID- 24885378
TI  - Inequalities in health status among rural residents: EQ-5D findings from
      household survey China.
AB  - INTRODUCTION: This study analyzed inequalities in health status among different
      socioeconomic and demographic rural residents covered by the New Rural
      Cooperative Medical System in China. METHODS: A cross-sectional study was
      conducted in Lian Yungang City, China. A total of 337 respondents, who were
      selected by using a multistage stratified systematic random sampling method,
      completed the surveys. A questionnaire consisting of EQ-5D and demographic and
      socioeconomic information was adopted for data collection, and was administered
      by face-to-face interviews. Multiple regression models were employed to examine
      the differences in the Visual Analogue Scale (VAS) score and the EQ-5D
      dimensions. RESULTS: Compared with those with lower education attainment, the
      respondents with higher education levels tended to report a higher VAS score
      (beta = 2.666, 95% CI: 0.978 to 6.310), and were less likely to suffer from
      pain/discomfort (OR = 3.968; 95% CI: 1.447 to 10.880). The singles were more
      likely than the married to report moderate or extreme problems in usual
      activities (OR = 4.583; 95% CI: 1.188 to 17.676) and mobility (OR = 10.666; 95%
      CI: 2.464 to 6.171). However, no statistically significant differences were
      identified between the respondents with different income levels in the VAS score
      and EQ-5D dimensions. CONCLUSIONS: This study suggests that the singles and the
      people with lower education levels are high-risk groups for poorer health status
      in the Chinese rural population. The findings from this study warrant further
      investigation.

PMID- 24885379
TI  - Significance of fractional exhaled nitric oxide in chronic eosinophilic
      pneumonia: a retrospective cohort study.
AB  - BACKGROUND: Chronic eosinophilic pneumonia (CEP) is characterized by chronic
      eosinophilic infiltration of the lung. It is dramatically responsive to
      corticosteroid treatment, but symptoms and radiopacities recur frequently after
      tapering or discontinuing the medication. Fractional exhaled nitric oxide (FeNO)
      is a well-known noninvasive marker of eosinophilic airway inflammation. The aim
      of this retrospective cohort study was to investigate the relationships of FeNO
      with peripheral eosinophilia and the clinical state of CEP and its validity for
      predicting exacerbation of CEP. METHODS: Standard clinical and laboratory
      parameters, peripheral eosinophil percentage and count, and FeNO level were
      measured in 18 patients with CEP at several assessment points over 1 year.
      RESULTS: FeNO level was positively correlated with peripheral eosinophil count (r
      = 0.341, P = 0.005) and percentage (r = 0.362, P = 0.003). The median (IQR) FeNO
      levels were 79 (41-88) and 35 (26-49) ppb in uncontrolled (13/74 measurements)
      and controlled (61/74 measurements) CEP, respectively (P = 0.010). The FeNO level
      of 66.0 ppb showed the largest area under the curve (0.835) for predicting
      exacerbation of CEP (sensitivity = 0.80, specificity = 0.84). CONCLUSION: FeNO
      may be useful for monitoring eosinophilic parenchymal inflammation and
      determining the appropriate corticosteroid dose in CEP.

PMID- 24885381
TI  - HECTOR: a parallel multistage homopolymer spectrum based error corrector for 454
      sequencing data.
AB  - BACKGROUND: Current-generation sequencing technologies are able to produce low
      cost, high-throughput reads. However, the produced reads are imperfect and may
      contain various sequencing errors. Although many error correction methods have
      been developed in recent years, none explicitly targets homopolymer-length errors
      in the 454 sequencing reads. RESULTS: We present HECTOR, a parallel multistage
      homopolymer spectrum based error corrector for 454 sequencing data. In this
      algorithm, for the first time we have investigated a novel homopolymer spectrum
      based approach to handle homopolymer insertions or deletions, which are the
      dominant sequencing errors in 454 pyrosequencing reads. We have evaluated the
      performance of HECTOR, in terms of correction quality, runtime and parallel
      scalability, using both simulated and real pyrosequencing datasets. This
      performance has been further compared to that of Coral, a state-of-the-art error
      corrector which is based on multiple sequence alignment and Acacia, a recently
      published error corrector for amplicon pyrosequences. Our evaluations reveal that
      HECTOR demonstrates comparable correction quality to Coral, but runs 3.7* faster
      on average. In addition, HECTOR performs well even when the coverage of the
      dataset is low. CONCLUSION: Our homopolymer spectrum based approach is
      theoretically capable of processing arbitrary-length homopolymer-length errors,
      with a linear time complexity. HECTOR employs a multi-threaded design based on a
      master-slave computing model. Our experimental results show that HECTOR is a
      practical 454 pyrosequencing read error corrector which is competitive in terms
      of both correction quality and speed. The source code and all simulated data are
      available at: http://hector454.sourceforge.net.

PMID- 24885380
TI  - Voluntary participation and comprehension of informed consent in a genetic
      epidemiological study of breast cancer in Nigeria.
AB  - BACKGROUND: Studies on informed consent to medical research conducted in low or
      middle-income settings have increased, including empirical investigations of
      consent to genetic research. We investigated voluntary participation and
      comprehension of informed consent among women involved in a genetic
      epidemiological study on breast cancer in an urban setting of Nigeria comparing
      women in the case and control groups. METHODS: Surveys were administered in face
      to-face interviews with 215 participants following their enrollment in the
      genetic study (106 patients, 109 controls). Audio-taped in-depth interviews were
      conducted with a sub-sample of 17 (8%) women who completed the survey. RESULTS:
      The majority of all participants reported being told that participation in the
      genetic study was voluntary (97%), that they did not feel pressured to
      participate in the study (99%), and that they could withdraw from the study
      (81%). The majority of the breast cancer patients (83%) compared to 58% of women
      in the control group reported that the study purpose was to learn about the
      genetic inheritance of breast cancer (OR 3.44; 95% CI =1.66, 7.14, p value =
      0.001). Most participants reported being told about study procedures (95%) and
      study benefits (98%). Sixty-eight percent of the patients, compared to 47% of the
      control group reported being told about study risks (p-value <0.001). Of the 165
      married women, 19% reported asking permission from their husbands to enroll in
      the breast cancer study; no one sought permission from local elders. In-depth
      interviews highlight the use of persuasion and negotiation between a wife and her
      husband regarding study participation. CONCLUSIONS: The global expansion of
      genetic and genomic research highlights our need to understand informed consent
      practices for studies in ethnically diverse cultural environments such as Africa.
      Quantitative and qualitative empirical investigations of the informed consent
      process for genetic and genomic research will further our knowledge of complex
      issues associated with communication of information, comprehension, decisional
      authority and voluntary participation. In the future, the development and testing
      of innovative strategies to promote voluntary participation and comprehension of
      the goals of genomic research will contribute to our understanding of strategies
      that enhance the consent process.

PMID- 24885383
TI  - Clinical impact of circulating miR-133, miR-1291 and miR-663b in plasma of
      patients with acute myocardial infarction.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is one of the leading causes for
      death in both developed and developing countries and it is the single largest
      cause of death in the United States, responsible for 1 out of every 6 deaths. The
      objective of this study was to determine microRNA (miRNA) expression in AMI and
      determine whether miR-133, miR-1291 and miR-663b could be measured in plasma as a
      biomarker for recurrence. METHODS: Patients with AMI and those without AMI were
      retrospectively recruited for a comparison of their plasma miR-133, miR-1291 and
      miR-663b expression. RESULTS: miR-133, miR-1291 and miR-663b levels were
      significantly overexpressed in AMI compared with Non-AMI. MiR-133 showed an AUC
      of 0.912, with a sensitivity of 81.1% and a specificity of 91.2%. The AUC for miR
      1291 was 0.695, with a sensitivity of 78.4% and a specificity of 89.5%. The AUC
      for miR-663b was 0.611, with a sensitivity of 72.4% and a specificity of 76.5%.
      CONCLUSIONS: This study demonstrated that the levels of miR-133, miR-1291 and miR
      663b are associated with AMI. The potential of these miRNAs as biomarkers to
      improve patient stratification according to the risk of AMI and as circulating
      biomarkers for the AMI progonos warrants further study. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/8183629061241474.

PMID- 24885382
TI  - Bobby Sox homology regulates odontoblast differentiation of human dental pulp
      stem cells/progenitors.
AB  - BACKGROUND: Transcription factors have been implicated in regulating the
      differentiation of odontoblasts from dental pulp stem cells/progenitors
      (DPSCs/progenitors), but their regulatory network is not completely understood.
      RESULT: New transcription factors that control the odontoblast differentiation of
      human DPSCs/progenitors were analyzed using a microarray. The result revealed
      bobby sox homolog (BBX) to be expressed most strongly during odontoblast
      differentiation. Validation using RT-PCR also revealed the strong expression of
      BBX during the odontoblast differentiation of DPSCs/progenitors. BBX expression
      was also detected in adult molar odontoblasts and other tissues, including the
      heart, kidney, testis, and bone marrow. To understand the role of BBX in
      odontoblast differentiation, BBX variant 1 and 2 cDNA were cloned and
      overexpressed in DPSCs/progenitors. The results showed that the overexpression of
      BBX cDNA in DPSCs/progenitors induced substantial mineralization and expression
      of the odontoblast marker genes, such as ALP, OPN, BSP, DMP1, and DSPP. The
      knockdown of BBX using shRNA, however, did not affect mineralization, but the
      expression of ALP and DSPP was decreased substantially. Meanwhile overexpression
      or knockdown of BBX did not modulate proliferation of DPSCs/progenitors.
      CONCLUSION: Our results suggest that BBX plays an important role during the
      odontoblast differentiation of human DPSCs/progenitors.

PMID- 24885384
TI  - Comparing short to standard duration of antibiotic therapy for patients
      hospitalized with cellulitis (DANCE): study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Recommended therapy duration for patients hospitalized with
      cellulitis is 10-14 days. Unnecessary use of antibiotics is one of the key
      factors driving resistance. Recent studies have shown that antibiotic therapy for
      cellulitis in outpatients can safely be shortened, despite residual inflammation.
      This study will compare in hospitalized patients the safety and effectiveness of
      shortening antibiotic therapy for cellulitis from 12 to 6 days. METHODS/DESIGN:
      In a multicenter, randomized, double-blind, non-inferiority trial, adult patients
      admitted with cellulitis will be included. Cellulitis is defined as warmth,
      erythema, and induration of the skin and/or subcutaneous tissue, with or without
      pain (including erysipelas). All patients will initially be treated with
      intravenous flucloxacillin, and will be evaluated after 5-6 days. Those who have
      improved substantially (defined as being afebrile, and having a lower cellulitis
      severity score) will be randomized at day 6 between additional 6 days of oral
      flucloxacillin (n = 198) or placebo (n = 198). Treatment success is defined as
      resolution of cellulitis on day 14 (disappearance of warmth and tenderness,
      improvement of erythema and edema), without the need of additional antibiotics
      for cellulitis by day 28. Secondary endpoints are relapse rate (up to day 90),
      speed of recovery (using a cellulitis severity score until day 28, and VAS scores
      on pain and swelling until day 90), quality of life (using the SF-36 and EQ-5D
      questionnaires) and costs (associated with total antibiotic use and health-care
      resource utilization up to day 90). DISCUSSION: Inclusion is planned to start in
      Q2 2014. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02032654) and the Netherlands
      Trial Register (NTR4360).

PMID- 24885385
TI  - Comparative transcriptome analysis of eggplant (Solanum melongena L.) and turkey
      berry (Solanum torvum Sw.): phylogenomics and disease resistance analysis.
AB  - BACKGROUND: Eggplant (Solanum melongena L.) and turkey berry (S. torvum Sw.), a
      wild ally of eggplant with promising multi-disease resistance traits, are of
      great economic, medicinal and genetic importance, but genomic resources for these
      species are lacking. In the present study, we sequenced the transcriptomes of
      eggplant and turkey berry to accelerate research on these two non-model species.
      RESULTS: We built comprehensive, high-quality de novo transcriptome assemblies of
      the two Leptostemonum clade Solanum species from short-read RNA-Sequencing data.
      We obtained 34,174 unigenes for eggplant and 38,185 unigenes for turkey berry.
      Functional annotations based on sequence similarity to known plant datasets
      revealed a distribution of functional categories for both species very similar to
      that of tomato. Comparison of eggplant, turkey berry and another 11 plant
      proteomes resulted in 276 high-confidence single-copy orthologous groups,
      reasonable phylogenetic tree inferences and reliable divergence time estimations.
      From these data, it appears that eggplant and its wild Leptostemonum clade
      relative turkey berry split from each other in the late Miocene, ~6.66 million
      years ago, and that Leptostemonum split from the Potatoe clade in the middle
      Miocene, ~15.75 million years ago. Furthermore, 621 and 815 plant resistance
      genes were identified in eggplant and turkey berry respectively, indicating the
      variation of disease resistance genes between them. CONCLUSIONS: This study
      provides a comprehensive transcriptome resource for two Leptostemonum clade
      Solanum species and insight into their evolutionary history and biological
      characteristics. These resources establish a foundation for further
      investigations of eggplant biology and for agricultural improvement of this
      important vegetable. More generally, we show that RNA-Seq is a fast, reliable and
      cost-effective method for assessing genome evolution in non-model species.

PMID- 24885386
TI  - Plasmid-mediated AmpC beta-lactamase (CMY-2) gene in Salmonella typhimurium
      isolated from diarrheic pigs in South Korea.
AB  - BACKGROUND: Salmonella resistant to third-generation cephalosporin has been
      isolated from an increasing number of animals worldwide. The purpose of this
      study was to examine ESBL (extended-spectrum beta-lactamases)-producing and PABL
      (plasmid-mediated AmpC beta-lactamases)-producing Salmonella isolates from pigs
      in South Korea. RESULTS: Salmonella Typhimurium KVCC-BA1300259 was resistant to
      ampicillin, amoxicillin/clavulanic acid, cephalothin, chloramphenicol,
      florfenicol, cefoxithin, gentamicin, nalidixic acid,
      trimethoprim/sulfamethoxazole, tetracycline, and ceftiofur. The results of a
      double-disk synergy test and PCR confirmed that the isolate produced CMY-2
      (PABL). Analysis of plasmid incompatibility (Inc) groups revealed the presence of
      IncA/C and IncFIB, indicating antimicrobial resistance. This study is the first
      to identify S. Typhimurium isolates harboring CMY-2 in pigs in South Korea.
      CONCLUSIONS: The presence of CMY-2 in pigs poses a significant threat of possible
      horizontal spread between animals and humans.

PMID- 24885387
TI  - Comparison of single coracoclavicular suture fixation and hook plate for the
      treatment of acute unstable distal clavicle fractures.
AB  - BACKGROUND: Surgical managements are recommended for unstable distal clavicle
      fractures because of a high incidence of nonunion. A variety of methods have been
      previously reported, but there is no current consensus regarding which method is
      the most suitable. METHODS: Between December 2004 and August 2010, we treated 68
      patients with Neer type IIB distal clavicle fractures using single
      coracoclavicular suture fixation with Mersilene tape (M group) or clavicular hook
      plate (H group). Sixty-eight patients were followed at least 24 months (mean,
      37.9 months). We retrospectively compared the functional outcome, parameters, and
      perioperative course of the two treatments. Statistical analysis was performed
      with independent sample t test and chi-square test. RESULTS: The M group
      presented significantly less operation time (P = 0.005) and intra-operative blood
      loss (P = 0.010) than the H group. The mean University of California at Los
      Angeles (UCLA) shoulder rating scale, Oxford shoulder score, VAS scale, and
      satisfaction score revealed no significant difference between the M group and the
      H group. The M group had better range of motion in the operated shoulder during
      forward flexion and abduction at 3 and 6 months postoperatively. However, the
      range of motion at 1 and 2 years after operation revealed almost the same
      results. Two acromial osteolysis and one acromial fracture were noted in the H
      group and one superficial wound infection and one frozen shoulder in the M group
      during follow-up. Finally, there was no significant difference in the
      complication rate between the two groups, and all fractures achieved union
      clinically at final follow-up. CONCLUSIONS: Both single coracoclavicular suture
      fixation and clavicular hook plate offered effective treatment in acute unstable
      distal clavicle fractures. However, single coracoclavicular suture fixation with
      Mersilene tape provided early recovery of shoulder motion and avoided further
      morbidity of the acromion.

PMID- 24885388
TI  - Increasing the effectiveness of the Diabetes Prevention Program through if-then
      plans: study protocol for the randomized controlled trial of the McGill CHIP
      Healthy Weight Program.
AB  - BACKGROUND: The Diabetes Prevention Program (DPP) is highly effective in
      promoting weight loss in overweight and obese individuals. However, one-on-one
      DPP sessions are costly. As a cost-saving alternative, a group version of the
      DPP, called Group Lifestyle Balance program (GLB), has been developed but has
      been shown to be less effective. The aim of this two-arm parallel randomized
      controlled trial is to increase the effectiveness of the GLB by integrating habit
      formation techniques, namely if-then plans and their mental practice, into the
      program. METHODS/DESIGN: A total of 154 participants will be randomized to a
      standard or enriched GLB program. For the enriched GLB program, if-then plans and
      their mental practice will be integrated into the standard GLB program.
      Participants will be overweight or obese men and women (BMI of 28 to 45 kg/m2,
      waist circumference >= 88 for women, >= 102 for men, 18 to 75 years of age) who
      do less than 200 minutes of self-reported moderate or vigorous exercise per week.
      Measures will be completed at baseline, 3 months, post-intervention (12 months),
      and 12 months post-intervention (24 months). The primary outcome measure is
      weight loss at 3, 12, and 24 months. Secondary outcomes include percent reaching
      weight loss goal, physical activity at 3, 12, and 24 months, and weight-related
      risk factors (waist circumference, hemoglobin A1c, systolic/diastolic blood
      pressure, total cholesterol/HDL ratio). Standardized training of the life-style
      coaches, use of standardized manuals, and audio taping and reviewing of the
      sessions will ensure intervention fidelity. DISCUSSION: The study will provide
      evidence-based data on the effectiveness of an enhanced GLB intervention in
      promoting weight loss and in reducing weight-related risk factors for chronic
      health problems. Ethical clearance has been received from the Research Ethics and
      Compliance Board of the Faculty of Medicine Research and Graduate Studies Office
      at McGill University (Montreal, Canada). TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT02008435. Registered 6 December 2013.

PMID- 24885389
TI  - Characterization of multi-drug tolerant persister cells in Streptococcus suis.
AB  - BACKGROUND: Persister cells constitute a subpopulation of dormant cells within a
      microbial population which are genetically identical but phenotypically different
      to regular cells. Notably, persister cells show an elevated tolerance to
      antimicrobial agents. Thus, they are considered to represent a microbial 'bet
      hedging' strategy and are of particular importance in pathogenic bacteria.
      RESULTS: We studied the ability of the zoonotic pathogen Streptococcus (S.) suis
      to form multi-drug tolerant variants and identified persister cells dependent on
      the initial bacterial growth phase. We observed lower numbers of persisters in
      exponential phase cultures than in stationary growth phase populations. S. suis
      persister cells showed a high tolerance to a variety of antibiotics, and the
      phenotype was not inherited as tested with four passages of S. suis populations.
      Furthermore, we provide evidence that the persister phenotype is related to
      expression of genes involved in general metabolic pathways since we found higher
      numbers of persister cells in a mutant strain defective in the catabolic arginine
      deiminase system as compared to its parental wild type strain. Finally, we
      observed persister cell formation also in other S. suis strains and pathogenic
      streptococcal species. CONCLUSIONS: Taken together, this is the first study that
      reports multi-drug tolerant persister cells in the zoonotic pathogen S. suis.

PMID- 24885391
TI  - "Knowledge and attitudes of Spanish adolescent girls towards human papillomavirus
      infection: where to intervene to improve vaccination coverage".
AB  - BACKGROUND: HPV vaccine coverage is far from ideal in Valencia, Spain, and this
      could be partially related to the low knowledge about the disease and the
      vaccine, therefore we assessed these, as well as the attitude towards vaccination
      in adolescent girls, and tried to identify independently associated factors that
      could potentially be modified by an intervention in order to increase vaccine
      coverage. METHODS: A cross sectional study was conducted in a random selection of
      schools of the Spanish region of Valencia. We asked mothers of 1278 girls, who
      should have been vaccinated in the 2011 campaign, for informed consent. Those
      that accepted their daughters' participation, a questionnaire regarding the
      Knowledge of HPV infection and vaccine was passed to the girls in the school.
      RESULTS: 833 mothers (65.1%) accepted participation. All their daughters'
      responded the questionnaire. Of those, 89.9% had heard about HPV and they
      associated it to cervical cancer. Only 14% related it to other problems like
      genital warts. The knowledge score of the girls who had heard about HPV was
      6.1/10. Knowledge was unrelated to the number of contacts with the health system
      (Pediatrician or nurse), and positively correlated with the discussions with
      classmates about the vaccine. Adolescents Spanish in origin or with an older
      sister vaccinated, had higher punctuation. 67% of the girls thought that the
      vaccine prevented cancer, and 22.6% felt that although prevented cancer the
      vaccine had important safety problems. 6.4% of the girls rejected the vaccine for
      safety problems or for not considering themselves at risk of infection. 71.5% of
      the girls had received at least one vaccine dose. Vaccinated girls scored higher
      knowledge (p = 0.05). CONCLUSION: Knowledge about HPV infection and vaccine was
      fair in adolescents of Valencia, and is independent to the number of contacts
      with the health system, it is however correlated to the conversations about the
      vaccine with their peers and the vaccination status. An action to improve HPV
      knowledge through health providers might increase vaccine coverage in the
      adolescents.

PMID- 24885390
TI  - Hippocampal neuronal cells that accumulate alpha-synuclein fragments are more
      vulnerable to Abeta oligomer toxicity via mGluR5--implications for dementia with
      Lewy bodies.
AB  - BACKGROUND: In dementia with Lewy bodies (DLB) abnormal interactions between
      alpha-synuclein (alpha-syn) and beta amyloid (Abeta) result in selective
      degeneration of neurons in the neocortex, limbic system and striatum. However,
      factors rendering these neurons selectively vulnerable have not been fully
      investigated. The metabotropic glutamate receptor 5 (mGluR5) has been shown to be
      up regulated in DLB and might play a role as a mediator of the neurotoxic effects
      of Abeta and alpha-syn in vulnerable neuronal populations. In this context, the
      main objective of the present study was to investigate the role of mGluR5 as a
      mediator of the neurotoxic effects of alpha-syn and Abeta in the hippocampus.
      RESULTS: We generated double transgenic mice over-expressing amyloid precursor
      protein (APP) and alpha-syn under the mThy1 cassette and investigated the
      relationship between alpha-syn cleavage, Abeta, mGluR5 and neurodegeneration in
      the hippocampus. We found that compared to the single tg mice, the alpha-syn/APP
      tg mice displayed greater accumulation of alpha-syn and mGluR5 in the CA3 region
      of the hippocampus compared to the CA1 and other regions. This was accompanied by
      loss of CA3 (but not CA1) neurons in the single and alpha-syn/APP tg mice and
      greater loss of MAP 2 and synaptophysin in the CA3 in the alpha-syn/APP tg.
      mGluR5 gene transfer using a lentiviral vector into the hippocampus CA1 region
      resulted in greater alpha-syn accumulation and neurodegeneration in the single
      and alpha-syn/APP tg mice. In contrast, silencing mGluR5 with a lenti-shRNA
      protected neurons in the CA3 region of tg mice. In vitro, greater toxicity was
      observed in primary hippocampal neuronal cultures treated with Abeta oligomers
      and over-expressing alpha-syn; this effect was attenuated by down-regulating
      mGluR5 with an shRNA lentiviral vector. In alpha-syn-expressing neuronal cells
      lines, Abeta oligomers promoted increased intracellular calcium levels, calpain
      activation and alpha-syn cleavage resulting in caspase-3-dependent cell death.
      Treatment with pharmacological mGluR5 inhibitors such as 2-Methyl-6
      (phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine
      (MTEP) attenuated the toxic effects of Abeta in alpha-syn-expressing neuronal
      cells. CONCLUSIONS: Together, these results support the possibility that
      vulnerability of hippocampal neurons to alpha-syn and Abeta might be mediated via
      mGluR5. Moreover, therapeutical interventions targeting mGluR5 might have a role
      in DLB.

PMID- 24885392
TI  - The association between maternal hepatitis B e antigen status, as a proxy for
      perinatal transmission, and the risk of hepatitis B e antigenaemia in Gambian
      children.
AB  - BACKGROUND: Early age at infection with hepatitis B virus (HBV) increases the
      risk of chronic HBV infection. In addition early age at infection may further
      increase the risk of persistent viral replication beyond its effect on
      chronicity. The effects of perinatal and early postnatal transmission on the risk
      of prolonged hepatitis B e antigenaemia in children with chronic HBV infection
      are not well documented in Africa. We examine these associations using maternal
      HBV sero-status and the number of HBV-positive older siblings as proxy measures
      for perinatal and early postnatal transmission, respectively. METHODS: Hepatitis
      B e antigen (HBeAg)-positive mothers were identified in six population-based HBV
      sero-surveys conducted in The Gambia between 1986 and 1990. For every HBeAg
      positive mother, a hepatitis B surface antigen (HBsAg)-positive HBeAg-negative
      mother and HBsAg-negative mother were randomly selected from the population
      surveyed. These mothers and their family members were tested for HBV sero-markers
      in a subsequent survey conducted between 1991 and 1993. RESULTS: Thirty-eight
      HBeAg positive mothers and the same number of HBsAg-positive HBeAg-negative
      mothers and HBsAg-negative mothers participated in the study. Sixty-nine percent
      of their children also participated. There was a non-significant positive
      association between HBeAg prevalence in children and the number of HBeAg-positive
      older siblings (64.1%, 69.2% and 83.3% in children with 0, 1 and >=2 HBeAg
      positive older siblings, respectively). After adjusting for confounders, having
      an HBeAg-positive mother was a risk factor for HBeAg positivity in children
      carrying HBsAg (adjusted OR 4.5, 95% CI: 1.0-19.5, p = 0.04), whilst the number
      of HBeAg-positive older siblings was not. CONCLUSIONS: Maternal HBeAg was
      associated with positive HBeAg in children with chronic HBV infection. This
      suggests that interrupting mother-to-infant transmission in sub-Saharan Africa
      might help reduce the burden of liver disease. A timely dose of HBV vaccine
      within 24 hours of birth, as recommended by WHO, should be implemented in sub
      Saharan Africa.

PMID- 24885393
TI  - Frequency and tendency of malaria in Colombia, 1990 to 2011: a descriptive study.
AB  - BACKGROUND: Malaria is a serious health problem in Colombia. This paper intends
      to analyse the frequency and tendencies of the disease in Colombia over the last
      22 years. The researchers used the Box-Jenkins (ARIMA) methodology for the
      analysis of time series. METHODS: This descriptive study was done retrospectively
      by using the morbidity records of the Ministry of Health and of the System for
      the Monitoring of Public Health (SIVIGILA). The information about the population
      was obtained from the National Administrative Department of Statistics (DANE).
      The incidence rate according to age and sex was calculated from 1990 to 2011.
      Also, the Annual Parasite Index (API) for Plasmodium falciparum and for
      Plasmodium vivax was calculated. The mortality rates per year, from 1990 to 2011,
      were determined. Finally, the Box-Jenkins (ARIMA) methodology was used for the
      analysis of time series, grouped weekly. Information for ARIMA modelling was used
      from the year 2001. RESULTS: The total number of reported cases from 1990 to 2011
      was 2,964,818 cases with an annual average of 134,764. In the period from 2001 to
      2005 and from 2006 to 2011 a significant decrease of annual cases was observed.
      In general, a predominance of P. vivax over P. falciparum was observed. With
      respect to the API, it must be noted that there were peaks in 1994 in the
      departments of Guainia and Guaviare, and in 1998 in Guaviare and Choco. The
      department of Antioquia showed a tendency towards a decrease of the API through
      the years.In the time series model there were no statistically significant
      seasonal patterns for the total number of cases of malaria. However, for P.
      falciparum the number of cases was statistically significant. Lastly, between
      1990 and 2009, there were 1,905 deaths caused by malaria in Colombia with a
      significant tendency towards a decrease in deaths over those years. Plasmodium
      falciparum was more lethal than P. vivax. CONCLUSIONS: In Colombia, the
      transmission of malaria occurs in an endemic and epidemic context, which keeps an
      unstable endemic transmission pattern. Several factors specific to a country such
      as Colombia encourage the dissemination and permanence of the illness.

PMID- 24885394
TI  - Performance evaluation of point-of-care test for detection of Cryptosporidium
      stool antigen in children and HIV infected adults.
AB  - BACKGROUND: Gastro-enteritis is associated with significant morbidity and
      mortality in patients with HIV/AIDS and children, and Cryptosporidium is the most
      important parasite implicated. To date, several commercial companies have
      developed simple and rapid point-of-care tests for the detection of
      Cryptosporidium infection; however, information is scarce regarding their
      diagnostic significance in Ethiopia. This study aimed at evaluating the
      performance of a rapid diagnostic test (RDT) for the detection of Cryptosporidium
      stool antigen. METHODS: A hospital-based cross-sectional study was conducted in
      Hawassa University Hospital, southern Ethiopia from May to November 2013. Faecal
      samples were collected from a total of 100 children and 250 HIV infected
      individuals with diarrhea or CD4 T-cell count lower than 200 cells/MUl. Specimens
      were processed using direct, formol-ether concentration and modified Ziehl
      Neelsen techniques for diagnosis of Cryptosporidium and other parasites. One
      hundred faecal samples (50 positives for Cryptosporidium, 35 positives for other
      parasites and 15 negatives for any intestinal parasites) were tested using the
      CoproStripTMCryptosporidium kit (Savyon Diagnostics Ltd, Israel). Test parameters
      were calculated using microscopy of the modified Ziehl-Neelsen stained stool
      smear as reference method. RESULTS: The performance of the RDT was first compared
      to routine microscopic analysis (examination <=10 min). The
      CoproStripTMCryptosporidium RDT correctly detected 31 of 42 positive samples and
      49 of 50 negative samples (i.e., 11 false negatives and 1 false positive).
      Sensitivity, specificity, PPV, NPV and accuracy were calculated to be 74, 98, 97,
      84 and 88%, respectively. Upon thorough microscopic analysis (examination >10
      min), 8 more samples with very low oocyst density were found. However, these were
      missed by the kit and lower the sensitivity and NPV to 62 and 72%, respectively.
      No cross-reactivity was observed with any of the helminthic or other protozoan
      parasites including Isospora and Cyclospora species. CONCLUSION: Based on the
      results described herein, the CoproStripTMCryptosporidium test could be used as
      an alternative to conventional microscopy especially where diagnosis of
      Cryptosporidium is limited due to time constraints, lack of experienced
      microscopists or unavailability of appropriate equipment/electricity.

PMID- 24885395
TI  - Up-regulation of CNDP2 facilitates the proliferation of colon cancer.
AB  - BACKGROUND: Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20
      metallopeptidases. It was stated in previous articles that higher expression
      levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study
      explored the correlation between CN2 and colon carcinogenesis. METHODS: We
      analysed the relationship between 183 patients clinicopathological
      characteristics and its CN2 expression. To detect the levels of CN2 in colon
      cancer cell lines and colon cancer tissues by western blot. To verify cell
      proliferation in colon cancer cells with knockdown of CNDP2 and explore the
      causes of these phenomena. RESULTS: The expression levels of CN2 in clinical
      colon tumors and colon cancer cell lines were significantly higher than that in
      normal colon mucosa and colon cell lines. The difference in CN2 levels was
      associated with tumor location (right- and left-sided colon cancer), but there
      was no significant association with age, gender, tumor size, tumor grade, tumor
      stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell
      proliferation, blocked cell cycle progression and retarded carcinogenesis in an
      animal model. The signaling pathway through which knockdown of CNDP2 inhibited
      cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E.
      CONCLUSIONS: Knockdown of CNDP2 can inhibit the proliferation of colon cancer in
      vitro and retarded carcinogenesis in vivo.

PMID- 24885396
TI  - Parent artery reconstruction for large or giant cerebral aneurysms using a
      Tubridge flow diverter (PARAT): study protocol for a multicenter, randomized,
      controlled clinical trial.
AB  - BACKGROUND: The treatment of large (10-25 mm) or giant (>=25 mm) cerebral
      aneurysms remains technically challenging, with a much higher complication and
      recanalization rate than that is observed for smaller aneurysms. The use of a
      flow diverter seems to facilitate the treatment of this special entity. In a
      previous single-center prospective study approved by the Ethics Committee and
      China Food and Drug Administration (CFDA), we obtained promising results, showing
      remarkable safety and effectiveness for the Tubridge flow diverter. Nevertheless,
      the previous study may have been limited by biases due to its single-center
      design and limited number of subjects. Furthermore, although various articles
      have reported durable results from treating aneurysms using flow diverters,
      increasing questions have arisen about this form of treatment. Thus, prospective,
      multiple-center, randomized trials containing more subjects are needed.
      METHODS/DESIGN: This study is a multicenter, randomized, controlled clinical
      trial comparing clinical outcomes for patients with unruptured large/giant
      intracranial aneurysms treated with either conventional stent-assisted coiling or
      flow diverter implantation. A total of 124 patients who fulfill the inclusion and
      exclusion criteria will be randomized into either a treatment group or a control
      group in the ratio of 1:1. The treatment group will receive Tubridge implantation
      alone or combined with bared coils, and the control group will be treated with
      stent-assisted coiling (bare coils). The primary endpoint will be the complete
      occlusion rate at 6-month follow-up. Secondary endpoints include the immediate
      technique success rate, overall mortality, adverse events (ischemic stroke or
      intracranial bleeding) within 30 days, 90 days and 1 year post-operation, and the
      rate of intra-stent stenosis and thrombosis 6 months post-operation. DISCUSSION:
      This prospective trial may provide more information on the safety and efficacy of
      the Tubridge flow diverter and may potentially change the strategy for treatment
      of large or giant aneurysms. TRIAL REGISTRATION: The trial is registered on the
      Chinese Clinical Trial Registry: ChiCTR-TRC-13003127.

PMID- 24885397
TI  - Cytokine levels as biomarkers of radiation fibrosis in patients treated with
      breast radiotherapy.
AB  - BACKGROUND: Radiation fibrosis is not easily measurable although clinical scores
      have been developed for this purpose. Biomarkers present an alternative more
      objective approach to quantification, and estimation in blood provides accessible
      samples. We investigated if blood cytokines could be used to measure established
      fibrosis in patients who have undergone radiotherapy for breast cancer. METHODS:
      We studied two cohorts treated by breast-conserving surgery and radiotherapy in
      the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal
      fibrosis (controls). Two candidate cytokines, plasma connective tissue growth
      factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons
      between cases and controls used the t-test or Mann-Whitney test and associations
      between blood concentration and clinical factors were assessed using the Spearman
      rank correlation coefficient. RESULTS: Seventy patients were included (26 cases,
      44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No
      statistically significant differences between cases and controls in serum IL6
      (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or
      plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were
      identified. There were no significant associations between blood cytokine
      concentration and age, fibrosis severity, breast size or time since radiotherapy.
      CONCLUSIONS: No significant difference in IL6 or CTGF concentrations was detected
      between patients with breast fibrosis and controls with minimal or no fibrosis.

PMID- 24885399
TI  - Physician communication in the operating room.
AB  - In this study, communication research was conducted with multidisciplinary groups
      of operating-room physicians. Theoretical frameworks from intercultural
      communication and rhetoric were used to (a) measure latent cultural communication
      variables and (b) conduct communication training with the physicians. A six-step
      protocol guided the research with teams of physicians from different surgical
      specialties: anesthesiologists, general surgeons, and obstetrician-gynecologists
      (n = 85). Latent cultural communication variables were measured by surveys
      administered to physicians before and after completion of the protocol. The
      centerpiece of the 2-hour research protocol was an instructional session that
      informed the surgical physicians about rhetorical choices that support
      participatory communication. Post-training results demonstrated scores increased
      on communication variables that contribute to collaborative communication and
      teamwork among the physicians. This study expands health communication research
      through application of combined intercultural and rhetorical frameworks, and
      establishes new ways communication theory can contribute to medical education. 

PMID- 24885400
TI  - Iron(III) sulfate as terminal oxidant in the synthesis of methyl ketones via
      Wacker oxidation.
AB  - An efficient and environmentally benign method using Fe(III) sulfate as a
      terminal oxidant in the synthesis of methyl ketones from terminal olefins via the
      Wacker process is developed. The methodology offers high selectivity for a
      Markonikov product, shows good functional group compatibility, involves mild
      reaction conditions, and is operationally simple. Fe2(SO4)3 is the sole terminal
      oxidant in this process. The method holds potential for future applications in
      organic synthesis. 

PMID- 24885398
TI  - GAS5 long non-coding RNA in malignant pleural mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer with
      short overall survival. Long non-coding RNAs (lncRNA) are a class of RNAs more
      than 200 nucleotides long that do not code for protein and are part of the 90% of
      the human genome that is transcribed. Earlier experimental studies in mice showed
      GAS5 (growth arrest specific transcript 5) gene deletion in asbestos driven
      mesothelioma. GAS5 encodes for a lncRNA whose function is not well known, but it
      has been shown to act as glucocorticoid receptor decoy and microRNA "sponge". Our
      aim was to investigate the possible role of the GAS5 in the growth of MPM.
      METHODS: Primary MPM cultures grown in serum-free condition in 3% oxygen or MPM
      cell lines grown in serum-containing medium were used to investigate the
      modulation of GAS5 by growth arrest after inhibition of Hedgehog or PI3K/mTOR
      signalling. Cell cycle length was determined by EdU incorporation assay in
      doxycycline inducible short hairpinGAS5 clones generated from ZL55SPT cells. Gene
      expression was quantified by quantitative PCR. To investigate the GAS5 promoter,
      a 0.77 kb sequence was inserted into a pGL3 reporter vector and luciferase
      activity was determined after transfection into MPM cells. Localization of GAS5
      lncRNA was identified by in situ hybridization. To characterize cells expressing
      GAS5, expression of podoplanin and Ki-67 was assessed by immunohistochemistry.
      RESULTS: GAS5 expression was lower in MPM cell lines compared to normal
      mesothelial cells. GAS5 was upregulated upon growth arrest induced by inhibition
      of Hedgehog and PI3K/mTOR signalling in in vitro MPM models. The increase in GAS5
      lncRNA was accompanied by increased promoter activity. Silencing of GAS5
      increased the expression of glucocorticoid responsive genes glucocorticoid
      inducible leucine-zipper and serum/glucocorticoid-regulated kinase-1 and
      shortened the length of the cell cycle. Drug induced growth arrest was associated
      with GAS5 accumulation in the nuclei. GAS5 was abundant in tumoral quiescent
      cells and it was correlated to podoplanin expression. CONCLUSIONS: The
      observations that GAS5 levels modify cell proliferation in vitro, and that GAS5
      expression in MPM tissue is associated with cell quiescence and podoplanin
      expression support a role of GAS5 in MPM biology.

PMID- 24885401
TI  - Reduced tolerance to abiotic stress in transgenic Arabidopsis overexpressing a
      Capsicum annuum multiprotein bridging factor 1.
AB  - BACKGROUND: The pepper fruit is the second most consumed vegetable worldwide.
      However, low temperature affects the vegetative development and reproduction of
      the pepper, resulting in economic losses. To identify cold-related genes
      regulated by abscisic acid (ABA) in pepper seedlings, cDNA representational
      difference analysis was previously performed using a suppression subtractive
      hybridization method. One of the genes cloned from the subtraction was homologous
      to Solanum tuberosum MBF1 (StMBF1) encoding the coactivator multiprotein bridging
      factor 1. Here, we have characterized this StMBF1 homolog (named CaMBF1) from
      Capsicum annuum and investigated its role in abiotic stress tolerance. RESULTS:
      Tissue expression profile analysis using quantitative RT-PCR showed that CaMBF1
      was expressed in all tested tissues, and high-level expression was detected in
      the flowers and seeds. The expression of CaMBF1 in pepper seedlings was
      dramatically suppressed by exogenously supplied salicylic acid, high salt,
      osmotic and heavy metal stresses. Constitutive overexpression of CaMBF1 in
      Arabidopsis aggravated the visible symptoms of leaf damage and the electrolyte
      leakage of cell damage caused by cold stress in seedlings. Furthermore, the
      expression of RD29A, ERD15, KIN1, and RD22 in the transgenic plants was lower
      than that in the wild-type plants. On the other hand, seed germination, cotyledon
      greening and lateral root formation were more severely influenced by salt stress
      in transgenic lines compared with wild-type plants, indicating that CaMBF1
      overexpressing Arabidopsis plants were hypersensitive to salt stress.
      CONCLUSIONS: Overexpression of CaMBF1 in Arabidopsis displayed reduced tolerance
      to cold and high salt stress during seed germination and post-germination stages.
      CaMBF1 transgenic Arabidopsis may reduce stress tolerance by downregulating
      stress-responsive genes to aggravate the leaf damage caused by cold stress.
      CaMBF1 may be useful for genetic engineering of novel pepper cultivars in the
      future.

PMID- 24885402
TI  - Nucleosome positioning and histone modifications define relationships between
      regulatory elements and nearby gene expression in breast epithelial cells.
AB  - BACKGROUND: The precise nature of how cell type specific chromatin structures at
      enhancer sites affect gene expression is largely unknown. Here we identified cell
      type specific enhancers coupled with gene expression in two different types of
      breast epithelial cells, HMEC (normal breast epithelial cells) and MDAMB231
      (triple negative breast cancer cell line). RESULTS: Enhancers were defined by
      modified neighboring histones [using chromatin immunoprecipitation followed by
      sequencing (ChIP-seq)] and nucleosome depletion [using formaldehyde-assisted
      isolation of regulatory elements followed by sequencing (FAIRE-seq)]. Histone
      modifications at enhancers were related to the expression levels of nearby genes
      up to 750 kb away. These expression levels were correlated with enhancer status
      (poised or active), defined by surrounding histone marks. Furthermore, about
      fifty percent of poised and active enhancers contained nucleosome-depleted
      regions. We also identified response element motifs enriched at these enhancer
      sites that revealed key transcription factors (e.g. TP63) likely involved in
      regulating breast epithelial enhancer-mediated gene expression. By utilizing
      expression data, potential target genes of more than 600 active enhancers were
      identified. These genes were involved in proteolysis, epidermis development, cell
      adhesion, mitosis, cell cycle, and DNA replication. CONCLUSIONS: These findings
      facilitate the understanding of epigenetic regulation specifically, such as the
      relationships between regulatory elements and gene expression and generally, how
      breast epithelial cellular phenotypes are determined by cell type specific
      enhancers.

PMID- 24885403
TI  - YB-1 regulates Sox2 to coordinately sustain stemness and tumorigenic properties
      in a phenotypically distinct subset of breast cancer cells.
AB  - BACKGROUND: Sox2, a transcription factor and an embryonic stem cell marker, has
      been implicated in the pathogenesis of breast cancer (BC). YB-1 is another
      transcription factor that has been shown to promote stemness in BC cells.
      METHODS: Western blotting, quantitative PCR, and siRNAs were used to query the
      regulatory relationships between YB-1, Sox2, and their downstream targets.
      Chromatin immunoprecipitation was used to detect YB-1 interactions at the Sox2
      promoter. Mammosphere and soft agar assays were used to assess the phenotypic
      consequences of YB-1 knockdown. RESULTS: Here, we report that YB-1 regulates
      Sox2. YB-1 was found to bind to the SOX2 promoter and down-regulate its
      expression in MCF7 and ZR751. The regulatory interaction between YB-1 and Sox2
      was drastically different between the two phenotypically distinct cell subsets,
      purified based on their differential response to a Sox2 reporter. They are
      referred to as the reporter unresponsive (RU) cells and the reporter responsive
      (RR) cells. Upon siRNA knockdown of YB-1, RU cells showed an increase in Sox2
      expression but no change in Sox2 reporter activity; in contrast, RR cells
      exhibited increased expression and reporter activity of Sox2. Correlating with
      these findings, YB-1 knockdown induced a differential response in the expression
      of genes known to be regulated by both Sox2 and YB-1 (e.g. CCND1 and ITGA6). For
      instance, in response to YB-1 knockdown, CCND1 and ITGA6 expression were
      decreased or unchanged in RU cells but paradoxically increased in RR cells.
      Compared to RU cells, RR cells were significantly more resistant to the
      suppression of mammosphere formation due to YB-1 knockdown. Importantly,
      mammospheres derived from parental MCF7 cells treated with YB-1 siRNA knockdown
      exhibited higher expression levels of SOX2 and its downstream targets.
      CONCLUSIONS: To conclude, in a subset of BC cells, namely RR cells, YB-1
      regulates Sox2 to coordinately maintain stemness and tumorigenic properties.

PMID- 24885404
TI  - Comparing the functional impact of knee replacements in two cohorts.
AB  - BACKGROUND: To examine if different rates of total knee replacement (TKR) in two
      similar cohorts with symptomatic knee osteoarthritis (OA) were associated with
      different functional impact of disease. METHODS: Subjects from the Multicenter
      Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI), persons with
      or at high risk of OA, had knee radiographs, completed Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) surveys and had TKRs confirmed
      at each visit. At each visit, subjects were defined as having symptomatic OA
      (SxOA) if >= one knee had pain and radiographic OA or if they had a TKR. WOMAC
      function scores at each visit were compared by analysis of covariance adjusting
      for age, sex, body mass index, race, site, depression, comorbidity, painful leg
      joints and knees affected. Post-TKR function scores were imputed to estimate
      scores that would have been present without TKR. RESULTS: Subjects with SxOA
      (n>750 in MOST and in OAI) had a mean age 66 to 67 years; most were women and
      were White. Subjects were followed 4-5 years. Among those with SxOA, more TKRs
      were done in MOST (35%) than OAI (19%). Adjusted mean WOMAC function (0-68, 68 =
      worst) improved from 26.9 to 21.9 in MOST and from 24.5 to 22.0 in OAI
      (difference between MOST and OAI in change in WOMAC function, p = .01). Estimates
      of function without TKRs showed function would not have changed in MOST (23.2 at
      baseline to 22.4). CONCLUSIONS: Functional status of subjects with knee OA in
      MOST improved more than in OAI, probably because of higher rates of TKRs. The
      decline suggests that TKR diminishes the functional impact of OA in the
      community.

PMID- 24885405
TI  - The transcriptome landscape of early maize meiosis.
AB  - BACKGROUND: A major step in the higher plant life cycle is the decision to leave
      the mitotic cell cycle and begin the progression through the meiotic cell cycle
      that leads to the formation of gametes. The molecular mechanisms that regulate
      this transition and early meiosis remain largely unknown. To gain insight into
      gene expression features during the initiation of meiotic recombination, we
      profiled early prophase I meiocytes from maize (Zea mays) using capillary
      collection to isolate meiocytes, followed by RNA-seq. RESULTS: We detected ~2,000
      genes as preferentially expressed during early meiotic prophase, most of them
      uncharacterized. Functional analysis uncovered the importance of several cellular
      processes in early meiosis. Processes significantly enriched in isolated
      meiocytes included proteolysis, protein targeting, chromatin modification and the
      regulation of redox homeostasis. The most significantly up-regulated processes in
      meiocytes were processes involved in carbohydrate metabolism. Consistent with
      this, many mitochondrial genes were up-regulated in meiocytes, including nuclear-
      and mitochondrial-encoded genes. The data were validated with real-time PCR and
      in situ hybridization and also used to generate a candidate maize homologue list
      of known meiotic genes from Arabidopsis. CONCLUSIONS: Taken together, we present
      a high-resolution analysis of the transcriptome landscape in early meiosis of an
      important crop plant, providing support for choosing genes for detailed
      characterization of recombination initiation and regulation of early meiosis. Our
      data also reveal an important connection between meiotic processes and
      altered/increased energy production.

PMID- 24885407
TI  - A formal concept analysis approach to consensus clustering of multi-experiment
      expression data.
AB  - BACKGROUND: Presently, with the increasing number and complexity of available
      gene expression datasets, the combination of data from multiple microarray
      studies addressing a similar biological question is gaining importance. The
      analysis and integration of multiple datasets are expected to yield more reliable
      and robust results since they are based on a larger number of samples and the
      effects of the individual study-specific biases are diminished. This is supported
      by recent studies suggesting that important biological signals are often
      preserved or enhanced by multiple experiments. An approach to combining data from
      different experiments is the aggregation of their clusterings into a consensus or
      representative clustering solution which increases the confidence in the common
      features of all the datasets and reveals the important differences among them.
      RESULTS: We propose a novel generic consensus clustering technique that applies
      Formal Concept Analysis (FCA) approach for the consolidation and analysis of
      clustering solutions derived from several microarray datasets. These datasets are
      initially divided into groups of related experiments with respect to a predefined
      criterion. Subsequently, a consensus clustering algorithm is applied to each
      group resulting in a clustering solution per group.These solutions are pooled
      together and further analysed by employing FCA which allows extracting valuable
      insights from the data and generating a gene partition over all the experiments.
      In order to validate the FCA-enhanced approach two consensus clustering
      algorithms are adapted to incorporate the FCA analysis. Their performance is
      evaluated on gene expression data from multi-experiment study examining the
      global cell-cycle control of fission yeast. The FCA results derived from both
      methods demonstrate that, although both algorithms optimize different clustering
      characteristics, FCA is able to overcome and diminish these differences and
      preserve some relevant biological signals. CONCLUSIONS: The proposed FCA-enhanced
      consensus clustering technique is a general approach to the combination of
      clustering algorithms with FCA for deriving clustering solutions from multiple
      gene expression matrices. The experimental results presented herein demonstrate
      that it is a robust data integration technique able to produce good quality
      clustering solution that is representative for the whole set of expression
      matrices.

PMID- 24885406
TI  - A network-based approach to identify substrate classes of bacterial
      glycosyltransferases.
AB  - BACKGROUND: Bacterial interactions with the environment- and/or host largely
      depend on the bacterial glycome. The specificities of a bacterial glycome are
      largely determined by glycosyltransferases (GTs), the enzymes involved in
      transferring sugar moieties from an activated donor to a specific substrate. Of
      these GTs their coding regions, but mainly also their substrate specificity are
      still largely unannotated as most sequence-based annotation flows suffer from the
      lack of characterized sequence motifs that can aid in the prediction of the
      substrate specificity. RESULTS: In this work, we developed an analysis flow that
      uses sequence-based strategies to predict novel GTs, but also exploits a network
      based approach to infer the putative substrate classes of these predicted GTs.
      Our analysis flow was benchmarked with the well-documented GT-repertoire of
      Campylobacter jejuni NCTC 11168 and applied to the probiotic model Lactobacillus
      rhamnosus GG to expand our insights in the glycosylation potential of this
      bacterium. In L. rhamnosus GG we could predict 48 GTs of which eight were not
      previously reported. For at least 20 of these GTs a substrate relation was
      inferred. CONCLUSIONS: We confirmed through experimental validation our
      prediction of WelI acting upstream of WelE in the biosynthesis of
      exopolysaccharides. We further hypothesize to have identified in L. rhamnosus GG
      the yet undiscovered genes involved in the biosynthesis of glucose-rich glycans
      and novel GTs involved in the glycosylation of proteins. Interestingly, we also
      predict GTs with well-known functions in peptidoglycan synthesis to also play a
      role in protein glycosylation.

PMID- 24885408
TI  - Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing
      tumor angiogenesis.
AB  - BACKGROUND: Vasohibin-2 (VASH2) has been identified as an endogenous and vascular
      endothelial growth factor (VEGF)-independent angiogenic factor that is highly
      expressed in tumor cells. In the present study, we aimed to determine whether pre
      existing vascular changes can be used to predict tumor transformation as benign
      or malignant. We sought to characterize microvascular changes and tumor
      development in the intestinal tract of ApcMin/+ mice and ApcMin/+/Vash2-/- mice.
      METHODS: ApcMin/+ mice provide a unique orthotopic model for the development of
      spontaneous adenomatous polyposis and subsequent carcinomas, a phenomenon termed
      the adenoma-carcinoma sequence. ApcMin/+ mice were mated with Vash2-/- mice with
      a mixed C57BL/6 background and the resulting pups were screened for the Min
      mutation and for the Vash2-/- gene by PCR. Intestinal tumors from ApcMin/+ mice
      and ApcMin/+/Vash2-/- mice were removed and either frozen or epon-embedded for
      subsequent analyses. For 3-dimensional imaging using confocal laser-scanning
      microscopy and transmission electron microscopy, cryosections were made, and
      immunofluorescent staining for various markers was performed. RESULTS: We found
      that structural abnormalities in tumor vessels from benign tumors resembled those
      in malignant tumors. In addition, a novel angiogenic factor, vasohibin-2 (VASH2)
      protein, was detected around tumor blood vessels in late-stage adenomas and
      adenocarcinomas, but was absent from early-stage adenomas in ApcMin/+ mice.
      Tumors used to examine endogenous VASH2 (derived from CMT93 colon carcinomas)
      were less vascularized in Vash2-/- mice and were more regular than those seen in
      wild-type (WT) mice. In addition, tumors in Vash2-/- mice were smaller than those
      in WT mice. Furthermore, cross-breeding of mice homozygous for a deletion of
      Vash2 with mice heterozygous for the APC mutation resulted in animals that showed
      a significant decrease in the number of polyps in the small intestine.
      CONCLUSION: We propose that VASH2 may modulate the onset of tumors in the
      gastrointestinal tract by regulating tumor angiogenesis.

PMID- 24885409
TI  - Communicating cardiovascular disease risk: an interview study of General
      Practitioners' use of absolute risk within tailored communication strategies.
AB  - BACKGROUND: Cardiovascular disease (CVD) prevention guidelines encourage
      assessment of absolute CVD risk - the probability of a CVD event within a fixed
      time period, based on the most predictive risk factors. However, few General
      Practitioners (GPs) use absolute CVD risk consistently, and communication
      difficulties have been identified as a barrier to changing practice. This study
      aimed to explore GPs' descriptions of their CVD risk communication strategies,
      including the role of absolute risk. METHODS: Semi-structured interviews were
      conducted with a purposive sample of 25 GPs in New South Wales, Australia.
      Transcribed audio-recordings were thematically coded, using the Framework
      Analysis method to ensure rigour. RESULTS: GPs used absolute CVD risk within
      three different communication strategies: 'positive', 'scare tactic', and
      'indirect'. A 'positive' strategy, which aimed to reassure and motivate, was used
      for patients with low risk, determination to change lifestyle, and some concern
      about CVD risk. Absolute risk was used to show how they could reduce risk. A
      'scare tactic' strategy was used for patients with high risk, lack of motivation,
      and a dismissive attitude. Absolute risk was used to 'scare' them into taking
      action. An 'indirect' strategy, where CVD risk was not the main focus, was used
      for patients with low risk but some lifestyle risk factors, high anxiety, high
      resistance to change, or difficulty understanding probabilities. Non-quantitative
      absolute risk formats were found to be helpful in these situations. CONCLUSIONS:
      This study demonstrated how GPs use three different communication strategies to
      address the issue of CVD risk, depending on their perception of patient risk,
      motivation and anxiety. Absolute risk played a different role within each
      strategy. Providing GPs with alternative ways of explaining absolute risk, in
      order to achieve different communication aims, may improve their use of absolute
      CVD risk assessment in practice.

PMID- 24885411
TI  - Treatment outcome of patients with comorbid type 1 diabetes and eating disorders.
AB  - BACKGROUND: Co-morbidity between Type 1 Diabetes Mellitus (T1DM) and eating
      disorders (ED) has been previously described; however the effect of this illness
      on the outcomes for conventional ED treatments has not been previously
      investigated. This study aims to compare clinical, psychopathological and
      personality features between two samples of ED individuals: those with comorbid
      T1DM and those without (No-DM); and to identify differences in treatment outcomes
      between the groups. METHODS: This study compares treatment outcome, dropouts, ED
      psychopathology and personality characteristics for 20 individuals with ED and
      T1DM and 20 ED patients without diabetes, matched for diagnostic and treatment
      type. RESULTS: The study found higher dropout rates from therapy in individuals
      with T1DM and worse treatment outcome in spite of having no significant
      differences in eating disorder psychopathology, although individuals with T1DM
      report misusing insulin. CONCLUSIONS: The low levels of motivation to change, and
      insulin abuse in T1DM patients, may suggest that treatment for patients with ED
      and T1DM should consider the individual's personality and role of insulin abuse
      when determining the appropriate intervention.

PMID- 24885410
TI  - Short-term mechanical stretch fails to differentiate human adipose-derived stem
      cells into cardiovascular cell phenotypes.
AB  - BACKGROUND: We and others have previously demonstrated that adipose-derived stem
      cells (ASCs) transplantation improve cardiac dysfunction post-myocardium
      infarction (MI) under hemodynamic stress in rats. The beneficial effects appear
      to be associated with pleiotropic factors due to a complex interplay between the
      transplanted ASCs and the microenvironment in the absence of cell
      transdifferentiation. In the present work, we tested the hypothesis that
      mechanical stretch per se could change human ASCs (hASCs) into cardiovascular
      cell phenotypes that might influence post-MI outcomes. METHODS: Human ASCs were
      obtained from patients undergoing liposuction procedures. These cells were
      stretched 12%, 1Hz up to 96 hours by using Flexercell 4000 system. Protein and
      gene expression were evaluated to identify cardiovascular cell markers. Culture
      medium was analyzed to determine cell releasing factors, and contraction
      potential was also evaluated. RESULTS: Mechanical stretch, which is associated
      with extracellular signal-regulated kinase (ERK) phosphorylation, failed to
      induce the expression of cardiovascular cell markers in human ASCs, and
      mesenchymal cell surface markers (CD29; CD90) remained unchanged. hASCs and
      smooth muscle cells (SMCs) displayed comparable contraction ability. In addition,
      these cells demonstrated a profound ability to secrete an array of cytokines.
      These two properties of human ASCs were not influenced by mechanical stretch.
      CONCLUSIONS: Altogether, our findings demonstrate that hASCs secrete an array of
      cytokines and display contraction ability even in the absence of induction of
      cardiovascular cell markers or the loss of mesenchymal surface markers when
      exposed to mechanical stretch. These properties may contribute to beneficial post
      MI cardiovascular outcomes and deserve to be further explored under the
      controlled influence of other microenvironment components associated with
      myocardial infarction, such as tissue hypoxia.

PMID- 24885413
TI  - Designing an intracellular fluorescent probe for glutathione: two modulation
      sites for selective signal transduction.
AB  - A selective probe for glutathione was designed and synthesized. The design
      incorporates spatial and photophysical constraints for the maximal emission
      signal. Thus, pHs, as well as the intracellular thiol concentrations, determine
      the emission signal intensity through a tight control of charge-transfer and PeT
      processes. The probe works satisfactorily inside the human breast adenocarcinoma
      cells, highlighting GSH distribution in the cytosol. 

PMID- 24885412
TI  - Non-invasive neuromodulation to improve gait in chronic multiple sclerosis: a
      randomized double blind controlled pilot trial.
AB  - BACKGROUND: This study sought to examine the effect of targeted physical therapy
      with and without cranial nerve non-invasive neuromodulation (CN-NINM), on the
      walking ability of people with MS who exhibited a dysfunctional gait. We
      hypothesized that subjects who received electrical stimulation would have greater
      improvement than those who had a control device after a 14-week intervention.
      Gait disturbance is a common problem for people with multiple sclerosis (MS).
      Current management may include exercise, pharmacology, functional electrical
      stimulation, compensatory strategies, use of assistive devices, and implanted
      electrical devices. We have developed an effective rehabilitative strategy using
      neuromodulation of the cranial nerves via electrical stimulation of the tongue to
      enhance the plasticity of the brain. METHODS: The study is a within-subject
      blinded randomized control design. Twenty chronic MS subjects with an identified
      gait disturbance were assigned to either an active or control group. Both groups
      completed a 14-week intervention program using a standardized combination of
      exercise and a device that provided electrical stimulation to the tongue. Those
      in the active group received electrical stimulation on the tongue that they could
      perceive. Those in the control group used a device that did not provide a
      physiologically significant stimulus and was not perceivable. Subjects were
      assessed with the Dynamic Gait Index (DGI). RESULTS: The DGI scores improved for
      both groups. There were significant between-group differences, with the active
      group showing statistically greater improvement than the control group mean.
      CONCLUSION: People with MS demonstrated improved gait with CN-NINM training in a
      pilot randomized controlled trial. This study suggests that tongue-based
      neurostimulation may amplify the benefits of exercise for improving gait in
      people with chronic MS.

PMID- 24885414
TI  - Evaluation of a 3A-truncated foot-and-mouth disease virus in pigs for its
      potential as a marker vaccine.
AB  - Foot-and-mouth disease (FMD) is a highly contagious and economically devastating
      disease of cloven-hoofed animals in the world. The disease can be effectively
      controlled by vaccination of susceptible animals with the conventional
      inactivated vaccine. However, one major concern of the inactivated FMD virus
      (FMDV) vaccine is that it does not allow serological discrimination between
      infected and vaccinated animals, and therefore interferes with serologic
      surveillance and the epidemiology of disease. A marker vaccine has proven to be
      of great value in disease eradication and control programs. In this study, we
      constructed a marker FMDV containing a deletion of residues 93 to 143 in the
      nonstructural protein 3A using a recently developed FMDV infectious cDNA clone.
      The marker virus, r-HN/3A93-143, had similar growth kinetics as the wild type
      virus in culture cell and caused a symptomatic infection in pigs. Pigs immunized
      with chemically inactivated marker vaccine were fully protected from the wild
      type virus challenge, and the potency of this marker vaccine was 10 PD50 (50% pig
      protective dose) per dose, indicating it could be an efficacious vaccine against
      FMDV. In addition, we developed a blocking ELISA targeted to the deleted epitope
      that could clearly differentiate animals infected with the marker virus from
      those infected with the wild type virus. These results indicate that a marker
      FMDV vaccine can be potentially developed by deleting an immunodominant epitope
      in NSP 3A.

PMID- 24885416
TI  - Detection of a divergent Parainfluenza 4 virus in an adult patient with influenza
      like illness using next-generation sequencing.
AB  - BACKGROUND: Human Parainfluenza viruses are a common cause of both upper and
      lower respiratory tract infections, particularly in children. Of the four
      Parainfluenza virus serotypes, Parainfluenza 4 is least well characterised from
      both the clinical, epidemiological and genetic perspectives. METHODS: Flocked
      nose or throat swabs from a previous study investigating viral prevalence in
      community-based adults suffering from influenza like illness were used as the
      basis for this study. Samples in which no virus was detected using a 16 viral
      respiratory pathogen real-time PCR panel were barcoded and pyrosequenced using
      the Roche 454 GS FLX Titanium chemistry. The sequences were analysed using the
      VirusHunter bioinformatic pipeline. Sanger sequencing was used to complete the
      detected Parainfluenza 4 coding region. RESULTS: A variant Parainfluenza 4
      subtype b strain (QLD-01) was discovered in an otherwise healthy adult who
      presented with influenza like illness. Strain QLD-01 shared genomic similarities
      with both a and b subtypes. The extent of divergence of this genome from the 5
      available whole Parainfluenza 4 genomes impacted the predicted binding
      efficiencies of the majority of published Parainfluenza 4 PCR assays.
      CONCLUSIONS: These findings further support a possible role for Parainfluenza 4
      in the aetiology of adult respiratory disease within the community setting, and
      highlight the caution needed to be used in designing PCR assays from limited
      sequence information or in using proprietary commercial PCR assays.

PMID- 24885415
TI  - Genotyping of Coxiella burnetii from domestic ruminants and human in Hungary:
      indication of various genotypes.
AB  - BACKGROUND: Information about the genotypic characteristic of Coxiella burnetii
      from Hungary is lacking. The aim of this study is to describe the genetic
      diversity of C. burnetii in Hungary and compare genotypes with those found
      elsewhere. A total of 12 samples: (cattle, n = 6, sheep, n = 5 and human, n = 1)
      collected from across Hungary were studied by a 10-loci multispacer sequence
      typing (MST) and 6-loci multiple-locus variable-number of tandem repeat analysis
      (MLVA). Phylogenetic relationships among MST genotypes show how these Hungarian
      samples are related to others collected around the world. RESULTS: Three MST
      genotypes were identified: sequence type (ST) 20 has also been identified in
      ruminants from other European countries and the USA, ST28 was previously
      identified in Kazakhstan, and the proposed ST37 is novel. All MST genotypes
      yielded different MLVA genotypes and three different MLVA genotypes were
      identified within ST20 samples alone. Two novel MLVA types 0-9-5-5-6-2 (AG) and 0
      8-4-5-6-2 (AF) (Ms23-Ms24-Ms27-Ms28-Ms33-Ms34) were defined in the ovine
      materials correlated with ST28 and ST37. Samples from different parts of the
      phylogenetic tree were associated with different hosts, suggesting host-specific
      adaptations. CONCLUSIONS: Even with the limited number of samples analysed, this
      study revealed high genetic diversity among C. burnetii in Hungary. Understanding
      the background genetic diversity will be essential in identifying and controlling
      outbreaks.

PMID- 24885417
TI  - Associations of cardiorespiratory fitness with cardiovascular disease risk
      factors in middle-aged Chinese women: a cross-sectional study.
AB  - BACKGROUND: High levels of physical activity (PA) and cardiorespiratory fitness
      (CRF) are each associated with a favorable cardiovascular disease (CVD) risk
      profile. However, the relationship between CRF and obesity is still inconsistent
      across studies, and there has been no thorough exploration of the independent
      contribution of CRF to different CVD risk factors in Chinese women. This study
      investigated the relationship between CRF and CVD risk factors in 40-49 year old
      women in Beijing. METHODS: The study included 231 urban-dwelling asymptomatic 40
      49 year old women. Body mass index (BMI), body fat percentage (BF%), blood
      glucose, blood lipids, blood pressure, and pulse wave velocity (PWV) were
      measured at rest. Cycle ergometer exercise tests were conducted to assess CRF as
      indicated by maximal oxygen uptake (VO(2max)). Participants were categorized into
      three CRF levels (low, moderate and high). RESULTS: High CRF level was associated
      with significantly less BF%, lower PWV, and higher weekly physical activity
      compared with low and moderate CRF (P < 0.05). Compared to high CRF, the odds
      ratios for having >=3 main CVD risk factors (overweight, hypertension, and
      dyslipidemia) in low and moderate CRF were 2.09 (95% CI: 1.48-2.94) and 1.84 (95%
      CI: 1.29-2.62), respectively. The proportion of participants with clinical ST
      segment depression and prolonged QTC interval during cycle ergometer testing was
      significantly higher in women with low CRF. CONCLUSIONS: Overall, Chinese middle
      aged women demonstrated a moderate level of CRF. CRF was independently associated
      with CVD risk factors, including overweight, hypertension, dyslipidemia, arterial
      stiffness, and abnormal ECG during exercise, with the least fit women exhibiting
      the highest number of CVD risk factors.

PMID- 24885419
TI  - Rehabilitation in a complex case of topographical disorientation.
AB  - This paper describes the rehabilitation process of a patient with severe
      topographical disorientation. The study demonstrates the sustained effects of a
      tailor-made, meticulous rehabilitation programme based on the gradual development
      of compensatory strategies. The patient (RB) had a memory impairment specific to
      environmental landmarks. He was able to recognise objects in his environment, but
      was unable to identify any salient object as a landmark and was also unable to
      derive any directional information from a chosen landmark. As such, his
      topographical disorientation syndrome was complex in that he had elements of both
      landmark agnosia and a heading disorientation, as described by Aguirre and
      D'Esposito (1999). Because of this dual damage to the exocentric framework, the
      tools and methods used in RB's rehabilitation programme were all based on his
      intact egocentric frame of reference. Remarkable training effects were found for
      routes he used frequently. After years of training he could walk these routes
      without the aid of the written information he had used previously, which can be
      interpreted as a form of implicit learning. In the 12 years we followed this
      patient some transfer occurred, as the patient was ultimately able to identify
      his own landmarks. However, RB remains dependent on other people to construct new
      routes for him on the basis of these landmarks.

PMID- 24885418
TI  - Laminin 411 acts as a potent inducer of umbilical cord mesenchymal stem cell
      differentiation into insulin-producing cells.
AB  - BACKGROUND: Diabetes mellitus (DM) is an incurable metabolic disease constituting
      a major threat to human health. Insulin-producing cells (IPCs) differentiated
      from mesenchymal stem cells (MSCs) hold great promise in the treatment of DM. The
      development of an efficient IPC induction system is a crucial step for the
      clinical application of IPCs for DM. Laminin 411 is a key component of the
      basement membrane and is involved in the regulation of cell differentiation;
      however, little is known about a role of laminin 411 in the regulation of IPC
      differentiation from human MSCs. METHODS: MSCs were isolated from human umbilical
      cord (UC-MSCs) and expanded in an in vitro culture system. UC-MSCs were then
      cultured in the IPC induction and differentiation medium in the presence of
      laminin 411. Flow cytometry, Quantitative realtime PCR, immunofluorescence
      staining, ELISA, Western blotting and other techniques were applied to determine
      IPC generation, insulin expression and related mechanisms. To evaluate potential
      therapeutic efficacy of IPCs induced from UC-MSCs, a type-1 diabetes (T1DM) rat
      model was generated using streptozotocin. Blood glucose, insulin levels, and
      survival of rats were monitored periodically following intravenous injection of
      the tested cells. RESULTS: Laminin 411 markedly induced the expression of the
      genes Foxa2 and Sox17, markers for pancreatic precursor cells, efficiently
      induced IPC differentiation from MSCs, and up-regulated insulin expression at
      both mRNA and protein levels. Furthermore, the expression of the genes known to
      govern insulin expression including Pdx1 and Ngn3 was markedly induced by laminin
      411, which suggests that Pdx1 and Ngn3 signaling pathways are involved in laminin
      411 induced-insulin expression machinery. More importantly, administration of
      laminin 411-induced IPCs rapidly and significantly down-regulated fasting blood
      glucose levels, significantly reduced the HbA1c concentration and markedly
      improved the symptoms and survival of T1DM rats. CONCLUSIONS: Our results
      demonstrate that laminin 411 acts as a potent differentiation inducer of IPCs
      from UC-MSCs via the Pdx1 and Ngn3 signaling pathways. Moreover, transfusion of
      laminin 411 induced-IPCs more efficiently improves symptoms and survival of T1DM
      rats. These novel finding highlights a potential clinical application of laminin
      411 induced-IPCs in the treatment of T1DM, which calls for further studies.

PMID- 24885420
TI  - The challenge to avoid anti-malarial medicine stock-outs in an era of funding
      partners: the case of Tanzania.
AB  - BACKGROUND: Between 2007 and 2013, the Tanzanian public sector received 93.1
      million doses of first-line anti-malarial artemisinin-based combination therapy
      (ACT) in the form of artemether-lumefantrine entirely supplied by funding
      partners. The introduction of a health facility ACT stock monitoring system using
      SMS technology by the National Malaria Control Programme in mid 2011 revealed a
      high frequency of stock-outs of ACT in primary care public health facilities. The
      objective of this study was to determine the pattern of availability of ACT and
      possible causes of observed stock-outs across public health facilities in
      Tanzania since mid-2011. METHODS: Data were collected weekly by the mobile phone
      reporting tool SMS for Life on ACT availability from over 5,000 public health
      facilities in Tanzania starting from September 2011 to December 2012. Stock data
      for all four age-dose levels of ACT across health facilities were summarized and
      supply of ACT at the national level was also documented. RESULTS: Over the period
      of 15 months, on average 29% of health facilities in Tanzania were completely
      stocked out of all four-age dose levels of the first-line anti-malarial with a
      median duration of total stock-out of six weeks. Patterns of total stock-out by
      region ranged from a low of 9% to a high of 52%. The ACT stock-outs were most
      likely caused by: a) insufficient ACT supplies entering Tanzania (e.g. in 2012
      Tanzania received 10.9 million ACT doses compared with a forecast demand of 14.4
      million doses); and b) irregular pattern of ACT supply (several months with no
      ACT stock). CONCLUSION: The reduced ACT availability and irregular pattern of
      supply were due to cumbersome bureaucratic processes and delays both within the
      country and from the main donor, the Global Fund to Fight AIDS, Tuberculosis and
      Malaria. Tanzania should invest in strengthening both the supply system and the
      health information system using mHealth solutions such as SMS for Life. This will
      continue to assist in tracking ACT availability across the country where all
      partners work towards more streamlined, demand driven and accountable procurement
      and supply chain systems.

PMID- 24885421
TI  - Histological complete response to a combined docetaxel/cisplatin/fluorouracil
      neoadjuvant chemotherapy for T4 stage gastric adenocarcinoma.
AB  - Local advanced gastric carcinoma has a very poor prognosis. When a T4 gastric
      carcinoma has invaded the surrounding tissues and organs, curative resection is
      unlikely. We present here a case of a 63-year-old woman with a T4 unresectable
      gastric adenocarcinoma. She underwent two 3-week cycles of
      docetaxel/cisplatin/fluorouracil chemotherapy, followed by radical gastric
      resection. Each cycle consisted of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin on
      day 1, and 200 mg/m2 leucovorin and 500 mg/m2 fluorouracil on days 1 through 5.
      The patient exhibited a complete histologic response. Our results indicate that
      docetaxel/cisplatin/fluorouracil neoadjuvant chemotherapy is a promising method
      of treatment for advanced gastric cancer. 

PMID- 24885422
TI  - Maghrebi minors as translators in health services in Tarragona (Spain): a
      qualitative study of the discourse of the Maghrebi adults.
AB  - BACKGROUND: In the province of Tarragona (Spain), 24% of immigrants come from
      countries in the Maghreb. 40% of Maghrebis residing in Spain say their linguistic
      command of Spanish is inadequate, which could hinder their relationship with
      healthcare professionals. The use of minors as translators by health services is
      a fairly common practice. The suitability of using children as translators has
      been questioned, although there has been little specific research on the subject
      and most has been from the perspective of professionals. The aim of this study
      was to qualitatively analyze the discourse of Maghrebi adults to the use of
      Maghrebi minors as translators in the health services. METHODS: A qualitative
      study using 12 in-depth interviews and 10 focus groups with Maghrebi adults
      living in Tarragona. The scope of the study was primary healthcare and hospital
      services in the area. A content analysis was performed using open coding.
      RESULTS: The practice studied is attributed to a lack of funding for translation
      resources, and prioritization of adults' work over children's education. It is
      seen as a convenient solution to the community's communication problems, although
      it is considered unreliable and detrimental to the rights of the child. The
      attitudes of healthcare professionals to the phenomenon studied varies from
      acceptance without any ethical concerns to concern about its effects on the
      child. The solutions proposed are the organization of translation resources with
      a proactive approach which are adapted to real needs, and a change in the focus
      of language training activities for the adults in the community. CONCLUSIONS: It
      is necessary to reconcile access to healthcare for Maghrebi adults with the
      rights of children who act as translators in the healthcare context. This
      requires coordination between health and educational institutions, changes in the
      organization and provision of translation resources, and a guarantee that
      immigrants have employment rights under the same conditions as Spanish nationals.

PMID- 24885423
TI  - Sidestream dark field images of the microcirculation: intra-observer reliability
      and correlation between two semi-quantitative methods for determining flow.
AB  - BACKGROUND: Since analysis of Sidestream Dark Field images still requires
      subjective interpretation, we wanted to determine intra-observer repeatability
      and to estimate the correlation between different evaluation methods. METHODS:
      Fifty-four Sidestream Dark Field videos were analyzed twice by the same blinded
      observer using validated software. Vessels were detected, generating the
      parameter Total Vessel Density (TVD), and flow was determined by (i) classifying
      each vessel separately, generating the parameters Perfused Vessel Density (PVD)
      and Proportion of Perfused Vessels (PPV), and by (ii) the "Boerma" method,
      generating a Microvascular Flow Index (MFI) by quadrants. RESULTS: Intraclass
      Correlation Coefficients (ICCs) were above 0.9 for TVD and above 0.8 for PDV and
      PPV. MFIby quadrants had the lowest reliability (ICC = 0.52 for capillaries and
      ICC = 0.59 for all vessels), significantly lower than for PVD (ICC = 0.89, p <
      0.001 for capillaries and ICC = 0.90, p < 0.001 for all vessels) and PPV (ICC =
      0.82, p = 0.003 for capillaries and ICC = 0.83, p = 0.01 for all vessels).
      Correlation coefficient (r) between PPV and MFIby quadrants corrected for
      measurement error was 0.39 (0.10 - 0.64) for capillaries and 1.01 (0.85 - 1.16)
      for all vessels. CONCLUSIONS: Intra-observer reliability for full evaluation of
      Sidestream Dark Field images was good for vessel detection and for flow
      classification but significantly poorer for the faster "Boerma" method.
      Furthermore, the Boerma method is likely to estimate different aspects of
      capillary flow than do the standard methods.

PMID- 24885424
TI  - Factors associated with non-utilisation of health service for childbirth in Timor
      Leste: evidence from the 2009-2010 Demographic and Health Survey.
AB  - BACKGROUND: Timor-Leste is a young developing country in Asia. Most of its
      infrastructure was destroyed after a long armed conflict for independence.
      Despite recent expansion of health facilities and investment in healthcare,
      maternal mortality remains high with most mothers still giving birth at home.
      This study investigated factors affecting the non-utilisation of health service
      for childbirth in the aftermath of the independence conflict. METHODS: The Timor
      Leste Demographic and Health Survey 2009-2010 was the latest two-stage national
      survey, which used validated questionnaires to obtain information from 26
      clusters derived from 13 districts of the country. Factors influencing non
      utilisation of health facility for childbirth were investigated using univariate
      and multivariable logistic regression analyses, accounting for the cluster
      sampling and sample weight of the survey. RESULTS: Of the total 5986 participants
      included in the study, 4472 (74.8%) did not deliver their last child at a health
      facility. Lack of education for the mother (adjusted odds ratio (OR): 2.04; 95%
      confidence interval (CI) 1.56 to 2.66) and her partner (OR: 1.45; 95% CI 1.14 to
      1.84), low household wealth status (OR: 5.20; 95% CI 3.93 to 6.90), and rural
      residence (OR: 2.83; 95% CI 2.22 to 3.66), were associated with increased
      likelihood of non-utilisation of health facility for childbirth. Working mothers
      (OR: 1.55; 95% CI 1.32 to 1.81), who had high parity (OR: 1.78; 95% CI 1.36 to
      2.32) and did not attend antenatal care service (OR: 4.68; 95% CI 2.65 to 8.28)
      were also vulnerable for not delivering at a health facility. Conversely, the
      prevalence of non-utilisation of health facility for childbirth reduced with
      increasing number of service components received during antenatal care visits
      (OR: 0.72; 95% CI 0.64 to 0.80). CONCLUSIONS: Only a quarter of Timorese women
      delivered at a health facility. In order to reduce maternal mortality, future
      interventions should target disadvantaged mothers from poor families, those
      residing in rural areas, have higher parity but no education, and who seldom
      attend antenatal care service, by improving their utilisation of health facility
      for childbirth.

PMID- 24885425
TI  - Identification of candidate risk gene variations by whole-genome sequence
      analysis of four rat strains commonly used in inflammation research.
AB  - BACKGROUND: The DA rat strain is particularly susceptible to the induction of a
      number of chronic inflammatory diseases, such as models for rheumatoid arthritis
      and multiple sclerosis. Here we sequenced the genomes of two DA sub-strains and
      two disease resistant strains, E3 and PVG, previously used together with DA
      strains in genetically segregating crosses. RESULTS: The data uncovers genomic
      variations, such as single nucleotide variations (SNVs) and copy number
      variations that underlie phenotypic differences between the strains. Comparisons
      of regional differences between the two DA sub-strains identified 8 genomic
      regions that discriminate between the strains that together cover 38 Mbp and
      harbor 302 genes. We analyzed 10 fine-mapped quantitative trait loci and our data
      implicate strong candidates for genetic variations that mediate their effects.
      For example we could identify a single SNV candidate in a regulatory region of
      the gene Il21r, which has been associated to differential expression in both rats
      and human MS patients. In the APLEC complex we identified two SNVs in a highly
      conserved region, which could affect the regulation of all APLEC encoded genes
      and explain the polygenic differential expression seen in the complex.
      Furthermore, the non-synonymous SNV modifying aa153 of the Ncf1 protein was
      confirmed as the sole causative factor. CONCLUSION: This complete map of genetic
      differences between the most commonly used rat strains in inflammation research
      constitutes an important reference in understanding how genetic variations
      contribute to the traits of importance for inflammatory diseases.

PMID- 24885426
TI  - The impact of televised tobacco control advertising content on campaign recall:
      evidence from the International Tobacco Control (ITC) United Kingdom Survey.
AB  - BACKGROUND: Although there is some evidence to support an association between
      exposure to televised tobacco control campaigns and recall among youth, little
      research has been conducted among adults. In addition, no previous work has
      directly compared the impact of different types of emotive campaign content. The
      present study examined the impact of increased exposure to tobacco control
      advertising with different types of emotive content on rates and durations of
      self-reported recall. METHODS: Data on recall of televised campaigns from 1,968
      adult smokers residing in England through four waves of the International Tobacco
      Control (ITC) United Kingdom Survey from 2005 to 2009 were merged with estimates
      of per capita exposure to government-run televised tobacco control advertising
      (measured in GRPs, or Gross Rating Points), which were categorised as either
      "positive" or "negative" according to their emotional content. RESULTS: Increased
      overall campaign exposure was found to significantly increase probability of
      recall. For every additional 1,000 GRPs of per capita exposure to negative
      emotive campaigns in the six months prior to survey, there was a 41% increase in
      likelihood of recall (OR = 1.41, 95% CI: 1.24-1.61), while positive campaigns had
      no significant effect. Increased exposure to negative campaigns in both the 1-3
      months and 4-6 month periods before survey was positively associated with recall.
      CONCLUSIONS: Increased per capita exposure to negative emotive campaigns had a
      greater effect on campaign recall than positive campaigns, and was positively
      associated with increased recall even when the exposure had occurred more than
      three months previously.

PMID- 24885427
TI  - AMPD1 rs17602729 is associated with physical performance of sprint and power in
      elite Lithuanian athletes.
AB  - BACKGROUND: The C34T genetic polymorphism (rs17602729) in the AMPD1 gene,
      encoding the skeletal muscle-specific isoform of adenosine monophosphate
      deaminase (AMPD1), is a common polymorphism among Caucasians that can impair
      exercise capacity. The aim of the present study was twofold: (1) to determine the
      C34T AMPD1 allele/genotype frequency distributions in Lithuanian athletes (n =
      204, stratified into three groups: endurance, sprint/power and mixed) and compare
      them with the allele/genotype frequency distributions in randomly selected
      healthy Lithuanian non-athletes (n = 260) and (2) to compare common
      anthropometric measurements and physical performance phenotypes between the three
      groups of athletes depending on their AMPD1 genotype. RESULTS: The results of our
      study indicate that the frequency of the AMPD1 TT genotype was 2.4% in the
      control group, while it was absent in the athlete group. There were significantly
      more sprint/power-orientated athletes with the CC genotype (86.3%) compared with
      the endurance-orientated athletes (72.9%), mixed athletes (67.1%), and controls
      (74.2%). We determined that the AMPD1 C34T polymorphism is not associated with
      aerobic muscle performance phenotype (VO2max). For CC genotype the short-term
      explosive muscle power value (based on Vertical Jump test) of athletes from the
      sprint/power group was significantly higher than that of the endurance group
      athletes (P < 0.05). The AMPD1 CC genotype is associated with anaerobic
      performance (Vertical Jump). CONCLUSIONS: The AMPD1 C allele may help athletes to
      attain elite status in sprint/power-oriented sports, and the T allele is a factor
      unfavourable for athletics in sprint/power-oriented sports categories. Hence, the
      AMPD1 C allele can be regarded as a marker associated with the physical
      performance of sprint and power. Replications studies are required to confirm
      this association.

PMID- 24885428
TI  - Demographic relevancy of increased use of assisted reproduction in European
      countries.
AB  - BACKGROUND: Delayed childbearing in European countries has resulted in an
      increase in the number of women having children later in life. Thus more women
      face the problem of age-related infertility and cannot achieve their desired
      number of children. Childbearing postponement is one of the main reasons for the
      increasing use of assisted reproductive technology (ART) and conversely, the
      latter may be one of the factors contributing to the rise in female childbearing
      age. The research goal of our article is to evaluate the demographic importance
      of ART increased use and to examine its impact on both the fertility rate and
      birth timing. METHODS: Comparative analysis based on demographic and ART data
      collected by the European IVF-monitoring (EIM) Consortium for the European
      Society of Human Reproduction and Embryology (ESHRE). RESULTS: Most countries
      with a higher total fertility rate (TFR) also registered a higher number of
      treatment cycles per 1 million women of reproductive age. Despite the positive
      relationship between the postponement rate and the demand for ART among women
      aged 35 and older, the highest share of children born after ART was not found in
      countries characterized by a "delayed" fertility schedule. Instead, the highest
      proportion of ART births was found in countries with fertility schedules
      concentrated on women aged between 25 and 34. Accordingly, the effective use of
      ART can be expected in populations with a less advanced postponement rate.
      CONCLUSIONS: ART can have a demographic relevancy when women take advantage of it
      earlier rather than later in life. Furthermore it is suggested that the use of
      ART at a younger age increases women's chance of achieving their reproductive
      goals and reduces the risk of age-related infertility and failed ART. Based on a
      demographic approach, reproductive health policy may become an integral part of
      policies supporting early childbearing: it may keep women from delaying too long
      having children and increase the chance of diagnosing potential reproductive
      health problems requiring a timely ART application.

PMID- 24885429
TI  - Obese older adults report high satisfaction and positive experiences with care.
AB  - BACKGROUND: Obese, older adults often have multiple chronic conditions resulting
      in multiple health care encounters. However, their satisfaction and experiences
      with care are not well understood. The objective of this study was to examine the
      independent impact of obesity on patient satisfaction and experiences with care
      in adults 65 years of age and older with Medigap insurance. METHODS: Surveys were
      mailed to 53,286 randomly chosen adults with an AARP(r) Medicare Supplement
      Insurance Plan insured by UnitedHealthcare Insurance Company (for New York
      residents, UnitedHealthcare Insurance Company of New York) in 10 states.
      Following adjustment for non-response bias, multivariate regression modeling was
      used to adjust for demographic, socioeconomic and health status differences to
      estimate the independent impact of weight on satisfaction and experiences with
      care. Outcome variables included four global and four composite measures of
      satisfaction and experiences with care. RESULTS: 21.4% of the respondents were
      obese. Relative to normal weight, obesity was significantly associated with
      higher patient satisfaction and better experiences with care in seven of the
      eight ratings measured. CONCLUSIONS: Obese individuals were more satisfied and
      had better experiences with care. Obese individuals had more office visits and
      discussions about nutrition, exercise and medical checks. This may have led to
      increased attentiveness to care, explaining the increase in satisfaction and
      better experiences with care. Given the high level of satisfaction and
      experiences with care in older, obese adults, opportunities exist for clinicians
      to address weight concerns in this population.

PMID- 24885430
TI  - Predictors of pathological complete response to neoadjuvant chemoradiotherapy for
      esophageal squamous cell carcinoma.
AB  - BACKGROUNDS: In this study, we evaluated the factors associated with a pathologic
      complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal
      squamous cell carcinoma (ESCC). METHODS: Pre-nCRT parameters in ESCC patients
      treated between 1999 and 2006 were analyzed to identify predictors of pCR. All
      patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam
      radiation followed by scheduled esophagectomy. Variables were analyzed using
      univariate and multivariate analyses with pCR as the dependent variable.
      Estimated pCR rate was calculated with a regression model. RESULTS: Fifty-nine
      (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient
      factors (age, smoking status, drinking history and hypertension), one pre-nCRT
      parameter (tumor length) as significant predictors of pCR (all P <0.05). On
      multivariate analysis, tumor length <=3 cm (favorable, odds ratio (OR): 4.85, P =
      0.001), patient age >55 years (favorable, OR: 1.95, P = 0.035), and being a non
      smoker (favorable, OR: 3.6, P = 0.003) were independent predictors of pCR. The
      estimated pCR rates based on a logistic regression including those three
      predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12%
      for patients with 3, 2, 1 and 0 predictors, respectively. CONCLUSION: Age,
      smoking habit and tumor length were important pCR predictors. These factors may
      be used to predict outcomes for ESCC patients receiving nCRT, to develop risk
      adapted treatment strategies, and to select patients who could participate in
      trials on new therapies.

PMID- 24885431
TI  - Diagnosis of genital herpes simplex virus infection in the clinical laboratory.
AB  - Since the type of herpes simplex virus (HSV) infection affects prognosis and
      subsequent counseling, type-specific testing to distinguish HSV-1 from HSV-2 is
      always recommended. Although PCR has been the diagnostic standard method for HSV
      infections of the central nervous system, until now viral culture has been the
      test of choice for HSV genital infection. However, HSV PCR, with its consistently
      and substantially higher rate of HSV detection, could replace viral culture as
      the gold standard for the diagnosis of genital herpes in people with active
      mucocutaneous lesions, regardless of anatomic location or viral type.
      Alternatively, antigen detection-an immunofluorescence test or enzyme immunoassay
      from samples from symptomatic patients--could be employed, but HSV type
      determination is of importance. Type-specific serology based on glycoprotein G
      should be used for detecting asymptomatic individuals but widespread screening
      for HSV antibodies is not recommended. In conclusion, rapid and accurate
      laboratory diagnosis of HSV is now become a necessity, given the difficulty in
      making the clinical diagnosis of HSV, the growing worldwide prevalence of genital
      herpes and the availability of effective antiviral therapy. 

PMID- 24885432
TI  - The Sticky Resting Box, a new tool for studying resting behaviour of Afrotropical
      malaria vectors.
AB  - BACKGROUND: Monitoring densities of adult mosquito populations is a major
      challenge in efforts to evaluate the epidemiology of mosquito-borne diseases, and
      their response to vector control interventions. In the case of malaria,
      collection of outdoor-resting Anophelines is rarely incorporated into
      surveillance and control, partially due to the lack of standardized collection
      tools. Such an approach, however, is increasingly important to investigate
      possible changes in mosquito behaviour in response to the scale up of Insecticide
      Treated Nets and Indoor Residual Spraying. In this study we evaluated the Sticky
      Resting Box (SRB) - i.e. a sticky variant of previously investigated mosquito
      Resting Box, which allows passive collection of mosquitoes entering the box - and
      compared its performance against traditional methods for indoor and outdoor
      resting mosquito sampling. METHODS: Daily collections were carried out in two
      neighbouring villages of Burkina Faso during rainy season 2011 and dry season
      2012 by SRB located indoors and outdoors, and by Back-Pack aspiration inside
      houses (BP) and in ad hoc built outdoor pit-shelters (PIT). RESULTS: Overall,
      almost 20,000 Culicidae specimens belonging to 16 species were collected and
      morphologically identified. Malaria vectors included Anopheles coluzzii (53%),
      An. arabiensis (12%), An. gambiae s.s. (2.0%) and An. funestus (4.5%). The
      diversity of species collected in the two villages was similar for SRB and PIT
      collections outdoors, and significantly higher for SRB than for BP indoors. The
      population dynamics of An. gambiae s.l. mosquitoes, as obtained by SRB
      collections was significantly correlated with those obtained by the traditional
      methods. The predicted mean estimates of An. gambiae s.l. specimens/sampling
      unit/night-of-collections was 6- and 5-times lower for SRB than for BP indoors
      and PIT outdoors, respectively. CONCLUSIONS: Overall, the daily performance of
      SRB in terms of number of malaria vectors/trap was lower than that of
      traditionally used approaches for in- and outdoor collections. However, unlike
      these methods, SRB could be set up to collect mosquitoes passively over at least
      a week. This makes SRB a promising tool for passively monitoring anopheline
      resting populations, with data presented here providing guidance for how to set
      up SRB-based collections to acquire information comparable to those obtained with
      other methods.

PMID- 24885434
TI  - Could digital patient communities be the launch pad for patient-centric trial
      design?
AB  - The system of medical discovery does not revolve around patients as unique
      individuals with preferences, needs, and desires. Rather it revolves around
      scientific scrutiny, the needs of the sponsor, and the desires for regulatory
      approval. The patient is only a subject. Is it any wonder, then, that some
      patients have rejected the current medical paradigm and sought to find their own
      path? 

PMID- 24885433
TI  - The effect of spinal curvature on the photogrammetric assessment on static
      balance in elderly women.
AB  - BACKGROUND: Involutional changes to the body in elderly patients affect the shape
      of the spine and the activity of postural muscles. The purpose of this study was
      to assess the influence of age-related changes in spinal curvature on postural
      balance in elderly women. METHODS: The study population consisted of 90 women,
      with a mean age of 70 +/- 8.01 years. Static balance assessments were conducted
      on a tensometric platform, and posturographic assessments of body posture were
      performed using a photogrammetric method based on the Projection Moire method.
      RESULTS: The results obtained were analysed using the Spearman's rank correlation
      coefficient test. We found a statistically significant correlation between body
      posture and the quality of the balance system response based on the corrective
      function of the visual system. The shape of the spinal curvature influenced
      postural stability, as measured by static posturography. Improvement in the
      quality of the balance system response depended on corrective information from
      the visual system and proprioceptive information from the paraspinal muscles.
      CONCLUSIONS: The sensitivity of the balance system to the change of centre of
      pressure location was influenced by the direction of the change in rotation of
      the shoulder girdle and spine. Development of spinal curvature in the sagittal
      plane and maintenance of symmetry in the coronal and transverse planes are
      essential for correct balance control, which in turn is essential for the
      development of a properly proportioned locomotor system.

PMID- 24885436
TI  - Implementing stakeholder-informed research in the substance abuse treatment
      sector: strategies used by Connections, a Canadian knowledge translation and
      exchange project.
AB  - BACKGROUND: Researcher-stakeholder collaboration has been identified as critical
      to bridging research and health system change. While collaboration models vary,
      meaningful stakeholder involvement over time ("integrated knowledge translation")
      is advocated to improve the relevance of research to knowledge users. This short
      report describes the integrated knowledge translation efforts of Connections, a
      knowledge translation and exchange project to improve services for women with
      substance abuse problems and their children, and implementation barriers and
      facilitators. FINDINGS: Strategies of varying intensities were used to engage
      diverse stakeholders, including policy makers and people with lived experience,
      and executive directors, program managers, and service providers from Canadian
      addiction agencies serving women. Barriers to participation included individual
      (e.g., interest), organizational (e.g., funding), and system level (e.g., lack of
      centralized stakeholder database) barriers. Similarly, facilitators included
      individual (e.g., perceived relevance) and organizational (e.g., support)
      facilitators, as well as initiative characteristics (e.g., multiple involvement
      opportunities). Despite barriers, Connections' stakeholder-informed research
      efforts proved essential for developing clinically relevant and feasible
      processes, measures, and implementation strategies. CONCLUSIONS: Stakeholder
      researcher collaboration is possible and robust integrated knowledge translation
      efforts can be productive. Future work should emphasize developing and evaluating
      a range of strategies to address stakeholders' knowledge translation needs and to
      facilitate sustained and meaningful involvement in research.

PMID- 24885435
TI  - Delayed neurogenesis leads to altered specification of ventrotemporal retinal
      ganglion cells in albino mice.
AB  - BACKGROUND: Proper binocular vision depends on the routing at the optic chiasm of
      the correct proportion of retinal ganglion cell (RGC) axons that project to the
      same (ipsilateral) and opposite (contralateral) side of the brain. The
      ipsilateral RGC projection is reduced in mammals with albinism, a congenital
      disorder characterized by deficient pigmentation in the skin, hair, and eyes.
      Compared to the pigmented embryonic mouse retina, the albino embryonic mouse
      retina has fewer RGCs that express the zinc-finger transcription factor, Zic2,
      which is transiently expressed by RGCs fated to project ipsilaterally. Here,
      using Zic2 as a marker of ipsilateral RGCs, Islet2 as a marker of contralateral
      RGCs, and birthdating, we investigate spatiotemporal dynamics of RGC production
      as they relate to the phenotype of diminished ipsilateral RGC number in the
      albino retina. RESULTS: At embryonic day (E)15.5, fewer Zic2-positive (Zic2+)
      RGCs are found in the albino ventrotemporal (VT) retina compared with the
      pigmented VT retina, as we previously reported. However, the reduction in Zic2+
      RGCs in the albino is not accompanied by a compensatory increase in Zic2-negative
      (Zic2-) RGCs, resulting in fewer RGCs in the VT retina at this time point. At
      E17.5, however, the number of RGCs in the VT region is similar in pigmented and
      albino retinae, implicating a shift in the timing of RGC production in the
      albino. Short-term birthdating assays reveal a delay in RGC production in the
      albino VT retina between E13 and E15. Specifically, fewer Zic2+ RGCs are born at
      E13 and more Zic2- RGCs are born at E15. Consistent with an increase in the
      production of Zic2- RGCs born at later ages, more RGCs at E17.5 express the
      contralateral marker, Islet2, in the albino VT retina compared with the pigmented
      retina. CONCLUSIONS: A delay in neurogenesis in the albino retina is linked to
      the alteration of RGC subtype specification and consequently leads to the reduced
      ipsilateral projection that characterizes albinism.

PMID- 24885437
TI  - Comparing the effect of clopidogrel versus ticagrelor on coronary microvascular
      dysfunction in acute coronary syndrome patients (TIME trial): study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: Although prompt reperfusion treatment restores normal epicardial
      flow, microvascular dysfunction may persist in some patients with acute coronary
      syndrome (ACS). Impaired myocardial perfusion is caused by intraluminal
      platelets, fibrin thrombi and neutrophil plugging; antiplatelet agents play a
      significant role in terms of protecting against thrombus microembolization. A
      novel antiplatelet agent, ticagrelor, is a non-thienopyridine, direct P2Y12
      blocker that has shown greater, more rapid and more consistent platelet
      inhibition than clopidogrel. However, the effects of ticagrelor on the prevention
      of microvascular dysfunction are uncertain. The present study is a comparison
      between clopidogrel and ticagrelor use for preventing microvascular dysfunction
      in patients with ST elevation or non-ST elevation myocardial infarction (STEMI or
      NSTEMI, respectively). METHODS/DESIGN: The TIME trial is a single-center,
      randomized, open-label, parallel-arm study designed to demonstrate the
      superiority of ticagrelor over clopidogrel. A total of 152 patients with a
      spectrum of STEMI or NSTEMI will undergo prospective random assignment to
      clopidogrel or ticagrelor (1:1 ratio). The primary endpoint is an index of
      microcirculatory resistance (IMR) measured after percutaneous coronary
      intervention (PCI); the secondary endpoint is wall motion score index assessed at
      3 months by using echocardiography. DISCUSSION: The TIME trial is the first study
      designed to compare the protective effect of clopidogrel and ticagrelor on
      coronary microvascular dysfunction in patients with STEMI and NSTEMI. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02026219. Registration date: 24 December
      2013.

PMID- 24885438
TI  - IMRT credentialing for prospective trials using institutional virtual phantoms:
      results of a joint European Organization for the Research and Treatment of Cancer
      and Radiological Physics Center project.
AB  - BACKGROUND AND PURPOSE: Intensity-modulated radiotherapy (IMRT) credentialing for
      a EORTC study was performed using an anthropomorphic head phantom from the
      Radiological Physics Center (RPC; RPC(PH)). Institutions were retrospectively
      requested to irradiate their institutional phantom (INST(PH)) using the same
      treatment plan in the framework of a Virtual Phantom Project (VPP) for IMRT
      credentialing. MATERIALS AND METHODS: CT data set of the institutional phantom
      and measured 2D dose matrices were requested from centers and sent to a dedicated
      secure EORTC uploader. Data from the RPC(PH) and INST(PH) were thereafter
      centrally analyzed and inter-compared by the QA team using commercially available
      software (RIT; ver.5.2; Colorado Springs, USA). RESULTS: Eighteen institutions
      participated to the VPP. The measurements of 6 (33%) institutions could not be
      analyzed centrally. All other centers passed both the VPP and the RPC +/-7%/4 mm
      credentialing criteria. At the 5%/5 mm gamma criteria (90% of pixels passing),
      11(92%) as compared to 12 (100%) centers pass the credentialing process with
      RPC(PH) and INST(PH) (p = 0.29), respectively. The corresponding pass rate for
      the 3%/3 mm gamma criteria (90% of pixels passing) was 2 (17%) and 9 (75%; p =
      0.01), respectively. CONCLUSIONS: IMRT dosimetry gamma evaluations in a single
      plane for a H&N prospective trial using the INST(PH) measurements showed
      agreement at the gamma index criteria of +/-5%/5 mm (90% of pixels passing) for a
      small number of VPP measurements. Using more stringent, criteria, the RPC(PH) and
      INST(PH) comparison showed disagreement. More data is warranted and urgently
      required within the framework of prospective studies.

PMID- 24885439
TI  - RNA-seq: impact of RNA degradation on transcript quantification.
AB  - BACKGROUND: The use of low quality RNA samples in whole-genome gene expression
      profiling remains controversial. It is unclear if transcript degradation in low
      quality RNA samples occurs uniformly, in which case the effects of degradation
      can be corrected via data normalization, or whether different transcripts are
      degraded at different rates, potentially biasing measurements of expression
      levels. This concern has rendered the use of low quality RNA samples in whole
      genome expression profiling problematic. Yet, low quality samples (for example,
      samples collected in the course of fieldwork) are at times the sole means of
      addressing specific questions. RESULTS: We sought to quantify the impact of
      variation in RNA quality on estimates of gene expression levels based on RNA-seq
      data. To do so, we collected expression data from tissue samples that were
      allowed to decay for varying amounts of time prior to RNA extraction. The RNA
      samples we collected spanned the entire range of RNA Integrity Number (RIN)
      values (a metric commonly used to assess RNA quality). We observed widespread
      effects of RNA quality on measurements of gene expression levels, as well as a
      slight but significant loss of library complexity in more degraded samples.
      CONCLUSIONS: While standard normalizations failed to account for the effects of
      degradation, we found that by explicitly controlling for the effects of RIN using
      a linear model framework we can correct for the majority of these effects. We
      conclude that in instances in which RIN and the effect of interest are not
      associated, this approach can help recover biologically meaningful signals in
      data from degraded RNA samples.

PMID- 24885440
TI  - An integrated approach for the in vitro dosimetry of engineered nanomaterials.
AB  - BACKGROUND: There is a great need for screening tools capable of rapidly
      assessing nanomaterial toxicity. One impediment to the development of reliable in
      vitro screening methods is the need for accurate measures of cellular dose. We
      present here a methodology that enables accurate determination of delivered to
      cell dose metrics. This methodology includes (1) standardization of engineered
      nanomaterial (ENM) suspension preparation; (2) measurement of ENM characteristics
      controlling delivery to cells in culture; and (3) calculation of delivered dose
      as a function of exposure time using the ISDD model. The approach is validated
      against experimentally measured doses, and simplified analytical expressions for
      the delivered dose (Relevant In Vitro Dose (RID)f function) are derived for 20
      ENMs. These functions can be used by nanotoxicologists to accurately calculate
      the total mass (RIDM), surface area (RIDSA), or particle number (RIDN) delivered
      to cells as a function of exposure time. RESULTS: The proposed methodology was
      used to derive the effective density, agglomerate diameter and RID functions for
      17 industrially-relevant metal and metal oxide ENMs, two carbonaceous
      nanoparticles, and non-agglomerating gold nanospheres, for two well plate
      configurations (96 and 384 well plates). For agglomerating ENMs, the measured
      effective density was on average 60% below the material density. We report great
      variability in delivered dose metrics, with some materials depositing within 24
      hours while others require over 100 hours for delivery to cells. A neutron
      activated tracer particle system was employed to validate the proposed in vitro
      dosimetry methodology for a number of ENMs (measured delivered to cell dose
      within 9% of estimated). CONCLUSIONS: Our findings confirm and extend
      experimental and computational evidence that agglomerate characteristics affect
      the dose delivered to cells. Therefore measurement of these characteristics is
      critical for effective use of in vitro systems for nanotoxicology. The mixed
      experimental/computational approach to cellular dosimetry proposed and validated
      here can be used by nanotoxicologists to accurately calculate the delivered to
      cell dose metrics for various ENMs and in vitro conditions as a function of
      exposure time. The RID functions and characterization data for widely used ENMs
      presented here can together be used by experimentalists to design and interpret
      toxicity studies.

PMID- 24885441
TI  - A negative effect of Campylobacter capsule on bacterial interaction with an
      analogue of a host cell receptor.
AB  - BACKGROUND: Campylobacter jejuni (C. jejuni) is the leading causative agent of
      bacterial gastrointestinal infections. The rise of antibiotic resistant forms of
      this pathogen necessitates the development of novel intervention strategies. One
      approach is the design of drugs preventing bacterial attachment to host cells.
      Although some putative C. jejuni adhesins have been identified, the molecular
      mechanisms of their interaction with host cells and their role in pathogenesis
      remain to be elucidated. C. jejuni adhesion may also be modulated by a bacterial
      capsule. However, the role of this structure in adhesion was not clear due to
      conflicting results published by different research groups. The aim of this study
      was to clarify the role of capsule in bacterial interaction with host cells by
      using an in vitro model of adhesion and an analogue of a host cell receptor.
      RESULTS: In this study, we developed an in vitro bacterial adhesion assay, which
      was validated using various tests, including competitive inhibition studies,
      exoglycosydase treatment and site-directed mutagenesis. We demonstrate that PEB3
      is one of the cell surface glycoproteins required for bacterial interaction with
      an analogue of a host cell receptor. In contrast, JlpA glycoprotein adhesin is
      not required for such interaction. We demonstrate that the production of capsule
      reduces bacterial attachment, and that the genes involved in capsule and PEB3
      adhesin biosynthesis are differentially regulated. CONCLUSIONS: In this study we
      report an in vitro model for the investigation of bacterial interaction with
      analogs of host cell receptors. The results suggest an interfering effect of
      capsule on bacterial attachment. In addition, using a liquid culture, we
      demonstrate differential expression of a gene involved in capsule production
      (kpsM) and a gene encoding a glycoprotein adhesin (peb3). Further studies are
      required in order to establish if these genes are also differentially regulated
      during the infection process. The results will assist in better understanding of
      the mechanism of pathogenesis of C. jejuni in general and the role of capsule in
      the process in particular.

PMID- 24885442
TI  - A pilot study of a practice management training module for medical residents.
AB  - BACKGROUND: In 2005 a competency based curriculum was introduced in the Dutch
      postgraduate medical training programs. While the manager's role is one of the
      seven key competencies, there is still no formal management course in most
      postgraduate curricula. Based on a needs assessment we conducted, several themes
      were identified as important for a possible management training program. We
      present the results of the pilot training we performed to investigate two of
      these themes. METHODS: The topics "knowledge of the healthcare system" and "time
      management" were developed from the list of suggested management training themes.
      Fourteen residents participated in the training and twenty-four residents served
      as control. The training consisted of two sessions of four hours with a homework
      assignment in between. 50 True/false-questions were given as pre- and post-test
      to both the test and control groups to assess the level of acquired knowledge
      among the test group as well as the impact of the intervention. We also performed
      a qualitative evaluation using evaluation forms and in-depth interviews. RESULTS:
      All fourteen residents completed the training. Six residents in the control group
      were lost to follow up. The pre- and post-test showed improvement among the
      participating residents in comparison to the residents from the control group,
      but this improvement was not significant. The qualitative assessment showed that
      all residents evaluated the training positively and experienced it as a useful
      addition to their training in becoming a medical specialist. CONCLUSION: Our
      training was evaluated positively and considered to be valuable. This study
      supports the need for mandatory medical management training as part of the
      postgraduate medical curriculum. Our training could be an example of how to teach
      two important themes in the broad area of medical management education.

PMID- 24885443
TI  - Solitary lymph node metastasis is a distinct subset of colon cancer associated
      with good survival: a retrospective study of surveillance, epidemiology, and end
      results population-based data.
AB  - BACKGROUND: Colon cancer with lymph node metastases has been considered as
      advanced stage and to have poor survival. We postulated that patients with
      solitary lymph node metastasis are a distinct subset with better colon cancer
      specific survival than those with multiple lymph node metastases. METHODS: In
      this retrospective study, we searched Surveillance, Epidemiology, and End-Results
      (SEER) population-based data and identified 86,674 patients who had been
      diagnosed with colon cancer without distant metastases and with less than three
      metastatic nodes between 1991 and 2005. We divided lymph node status into three
      subgroups: pN0, pN1a, and pN1b and obtained 5-year colon cancer-specific survival
      for each pT stage. We used Kaplan-Meier and multivariate Cox regression models to
      assess correlations between risk factors and survival outcomes. RESULTS: Analysis
      of SEER data confirmed that patients with solitary lymph node metastases had
      better 5-year cancer-specific survival than pN1b according to both univariate and
      multivariate analysis. This finding was confirmed by further analyses in five pT
      subgroups. Cancer-specific survival of patients with pT1-2N1a was comparable to
      that of those with pIIA but higher than those with pIIB. In addition, survival of
      patients with pT3-4aN1a was better than those with pIIC. CONCLUSION: Colon cancer
      patients with solitary lymph node metastasis are a distinct subset with a
      favorable prognosis; full consideration should be given to this in clinical
      practice.

PMID- 24885444
TI  - Calprotectin in cystic fibrosis.
AB  - BACKGROUND: There is increasing evidence that intestinal inflammation plays a
      major role in gastrointestinal symptoms in cystic fibrosis (CF). Fecal
      calprotectin is a marker that is elevated in several gastrointestinal
      inflammatory diseases, but little is known about its value in CF. We aimed to
      look for associations of elevated fecal calprotectin among CF patients and
      whether its level correlates with the clinical manifestations of CF. METHODS: A
      single stool specimen was collected from 62 patients with CF. Fecal calprotectin
      was measured using the commercially available ELISA kits (PhiCalTM test).
      Clinical data were collected from patients' records and CF registry. RESULTS:
      There were no significant differences between CF patients with normal and
      abnormal fecal calprotectin levels. However, patients who were not receiving
      inhaled antibiotics had higher fecal calprotectin levels than those who were.
      CONCLUSION: Elevated fecal calprotectin may not accurately predict intestinal
      inflammation in CF. However, the fact that it was elevated in both pancreatic
      sufficient and insufficient groups supports the concept of "cystic fibrosis
      enteropathy" regardless of the pancreatic status.

PMID- 24885445
TI  - Chronic periaortitis (retroperitoneal fibrosis) concurrent with giant cell
      arteritis: a case report.
AB  - INTRODUCTION: Giant cell arteritis is the most common form of large-vessel
      vasculitides. However, it is probable that extracranial involvement is
      underdiagnosed in patients with classical giant cell arteritis. In the recent
      literature most cases of giant cell arteritis have been described in conjunction
      with aortic aneurysms or dissections. Nonetheless the coexistence of giant cell
      arteritis and retroperitoneal fibrosis is extremely rare. Here, we describe a
      case of giant cell arteritis at a very early clinical stage, in a woman with
      coexistence of retroperitoneal fibrosis. CASE PRESENTATION: We report a case of
      giant cell arteritis at a very early clinical stage, in a 47-year-old Greek woman
      with coexistence of retroperitoneal fibrosis who was admitted to our hospital
      with a history of high-grade fever and mild right periumbilical abdominal pain
      for the past 30 days. In the context of fever of unknown origin, an abdomen
      computed tomography was ordered. A temporal artery biopsy was also performed
      because during hospitalization she complained of a headache. Examination of eosin
      and hematoxylin slides from biopsy specimens of her temporal artery, showed
      lesions consisting of predominantly lymphocytes, few plasma cells and occasional
      polymorphonuclear leucocytes. In addition no giant cells were detected in
      examining biopsies at multiple levels. This was consistent with giant cell
      arteritis according to the American college of Rheumatology criteria. An abdomen
      computed tomography revealed the presence of a retroperitoneal soft-tissue mass
      located anteriorly to the upper infrarenal aorta at the site of the scintigraphic
      uptake. The computed tomography and magnetic resonance imaging characteristics of
      the mass were consistent with retroperitoneal fibrosis, and its morphology
      suggestive of benignity. Our patient started oral prednisolone and was afebrile
      from day one. CONCLUSIONS: In our experience this is the first case of
      retroperitoneal fibrosis due to giant cell arteritis occurring at the same time.
      Involvement of the aorta (aortitis) and its branches has been also observed in a
      subset of patients with giant cell arteritis. In addition, giant cell arteritis
      has been associated with a markedly increased risk of aortic aneurysm
      particularly thoracic aortic aneurysm.

PMID- 24885446
TI  - Polygonum viviparum L. induces vasorelaxation in the rat thoracic aorta via
      activation of nitric oxide synthase in endothelial cells.
AB  - BACKGROUND: In the past several decades, Polygonum viviparum L. (PV) was reported
      to have antibacterial, antiulcer, antioxidant, antitumor, anti-inflammatory, and
      antiarthritic properties. The anti-inflammatory pathway was recently elucidated
      through cytosolic nuclear factor E2-related factor 2 (Nrf2) activation and heme
      oxygenase (HO)-1 protein expression. PV is a perennial herb and widely
      distributed in high-elevation mountain regions, such as the Tibetan Plateau. In
      Tibetan traditional medicine, PV is usually used to boost the blood circulation
      to dissipate blood stasis. Therefore, this study focused on how PV improves the
      vascular circulation and acts on vascular tissues. METHODS: In this study, we
      isolated aortas from Sprague-Dawley rats (male, weight about 250~350 g), and
      detected the effects of PV on phenylephrine (PE)-induced contraction and cyclic
      guanosine 3',5'-monophosphate (cGMP) formation using aortic rings. In addition,
      human umbilical vein endothelial cells (HUVECs) were used to exam nitric oxygen
      (NO) synthase (NOS) activity by directly measuring NO production in the culture
      medium. Endothelial (e) NOS phosphorylation, and cytosolic Nrf2 and HO-1
      expressions were measured using a Western blot analysis. RESULTS: PV dose
      dependently relaxed PE-induced contractions in endothelial-intact but not 
      denuded aorta. The concentration to produce 50% relaxation was 22.04+/-1.77
      MUg/ml. PV-induced vasorelaxation was markedly blocked by pretreatment with NG
      nitro-L-arginine methyl ester (L-NAME), an NOS inhibitor, methylene blue (MB), a
      guanylyl cyclase inhibitor, and hemoglobin, an NO scavenger. PV increased cGMP
      formation; however, this effect was also suppressed by co-pretreatment with l
      NAME, MB, hemoglobin, and Ca2+-free medium. In HUVECs, PV increased NO formation,
      which was greatly attenuated by NOS inhibitors (L-NAME and L-NMMA) and by
      removing extracellular Ca2+ and chelating intracellular Ca2+ with BAPTA-AM. In
      addition, PV promoted eNOS phosphorylation, Nrf2 degradation, and HO-1 protein
      expression according to a Western blot analysis. CONCLUSIONS: The results suggest
      that PV possesses vasorelaxing action in an endothelium-dependent manner and
      works through activating Ca2+/calmodulin- dependent NO synthesis; when NO is
      released and then transferred to smooth muscle cells, NO activates guanylyl
      cyclase and increases cGMP formation, ultimately resulting in vasorelaxation.
      Thus, PV can be considered for application as a potential therapeutic approach
      for vascular-associated disorders.

PMID- 24885448
TI  - Social perception in adults with Parkinson's disease.
AB  - OBJECTIVE: Our study assessed how nondemented patients with Parkinson's disease
      (PD) interpret the affective and mental states of others from spoken language
      (adopt a "theory of mind") in ecologically valid social contexts. A secondary
      goal was to examine the relationship between emotion processing, mentalizing, and
      executive functions in PD during interpersonal communication. METHOD: Fifteen
      adults with PD and 16 healthy adults completed The Awareness of Social Inference
      Test, a standardized tool comprised of videotaped vignettes of everyday social
      interactions (McDonald, Flanagan, Rollins, & Kinch, 2003). Individual subtests
      assessed participants' ability to recognize basic emotions and to infer speaker
      intentions (sincerity, lies, sarcasm) from verbal and nonverbal cues, and to
      judge speaker knowledge, beliefs, and feelings. A comprehensive
      neuropsychological evaluation was also conducted. RESULTS: Patients with mild
      moderate PD were impaired in the ability to infer "enriched" social intentions,
      such as sarcasm or lies, from nonliteral remarks; in contrast, adults with and
      without PD showed a similar capacity to recognize emotions and social intentions
      meant to be literal. In the PD group, difficulties using theory of mind to draw
      complex social inferences were significantly correlated with limitations in
      working memory and executive functioning. CONCLUSIONS: In early PD, functional
      compromise of the frontal-striatal-dorsal system yields impairments in social
      perception and understanding nonliteral speaker intentions that draw upon
      cognitive theory of mind. Deficits in social perception in PD are exacerbated by
      a decline in executive resources, which could hamper the strategic deployment of
      attention to multiple information sources necessary to infer social intentions.

PMID- 24885447
TI  - Nucleotide excision repair/transcription gene defects in the fetus and impaired
      TFIIH-mediated function in transcription in placenta leading to preeclampsia.
AB  - BACKGROUND: Preeclampsia is a significant cause of maternal and fetal mortality
      and morbidity worldwide. We previously reported associations between
      trichothiodystrophy (TTD) nucleotide excision repair (NER) and transcription gene
      mutations in the fetus and the risk of gestational complications including
      preeclampsia. TTD NER/transcription genes, XPD, XPB and TTD-A, code for subunits
      of Transcription Factor (TF)IIH. Interpreting XPD mutations in the context of
      available biochemical data led us to propose adverse effects on CDK-activating
      kinase (CAK) subunit of TFIIH and TFIIH-mediated functions as a relevant
      mechanism in preeclampsia. In order to gain deeper insight into the underlying
      biologic mechanisms involving TFIIH-mediated functions in placenta, we analyzed
      NER/transcription and global gene expression profiles of normal and preeclamptic
      placentas and studied gene regulatory networks. RESULTS: We found high expression
      of TTD NER/transcription genes in normal human placenta, above the mean of their
      expression in all organs. XPD and XPB were consistently expressed from 14 to 40
      weeks gestation while expression of TTD-A was strongly negatively correlated (r=
      0.7, P<0.0001) with gestational age. Analysis of gene expression patterns of
      placentas from a case-control study of preeclampsia using Algorithm for
      Reconstruction of Accurate Cellular Networks (ARACNE) revealed GTF2E1, a
      component of TFIIE which modulates TFIIH, among major regulators of
      differentially-expressed genes in preeclampsia. The basal transcription pathway
      was among the largest dysregulated protein-protein interaction networks in this
      preeclampsia dataset. Within the basal transcription pathway, significantly down
      regulated genes besides GTF2E1 included those coding for the CAK complex of
      TFIIH, namely CDK7, CCNH, and MNAT1. Analysis of other relevant gene expression
      and gene regulatory network data also underscored the involvement of
      transcription pathways and identified JUNB and JUND (components of transcription
      factor AP-1) as transcription regulators of the network involving the TTD genes,
      GTF2E1, and selected gene regulators implicated in preeclampsia. CONCLUSIONS: Our
      results indicate that TTD NER/transcription genes are expressed in placenta
      during gestational periods critical to preeclampsia development. Our overall
      findings suggest that impairment of TFIIH-mediated function in transcription in
      placenta is a likely mechanism leading to preeclampsia and provide etiologic
      clues which may be translated into therapeutic and preventive measures.

PMID- 24885449
TI  - Remote thalamic microstructural abnormalities related to cognitive function in
      ischemic stroke patients.
AB  - OBJECTIVE: Ischemic stroke can lead to a continuum of cognitive sequelae, ranging
      from mild vascular cognitive impairment to vascular dementia. These cognitive
      deficits can be influenced by the disruption of cortico-subcortical circuits. We
      sought to explore remote thalamic microstructural abnormalities and their
      association with cognitive function after ischemic stroke. METHOD: Seventeen
      patients with right hemispheric ischemic stroke and 17 controls matched for age,
      sex, and years of education were included. All participants underwent
      neurological, neuropsychological, and diffusion tensor image examination.
      Patients were assessed 3 months poststroke. Voxel-wise analysis was used to study
      thalamic diffusion differences between groups. Mean fractional anisotropy (FA)
      and mean diffusivity (MD) values in significant thalamic areas were calculated
      for each subject and correlated with cognitive performance. RESULTS: Stroke
      patients showed lower FA values and higher MD values in specific areas of both
      the left and right thalamus compared with controls. In patients, decreased FA
      values were associated with lower verbal fluency performance in the right
      thalamus (R(2) = 0.45, beta = 0.74) and the left thalamus (R(2) = 0.57, beta =
      0.77) after adjusting for diabetes mellitus. Moreover, increased MD values were
      associated with lower verbal fluency performance in the right thalamus (R(2) =
      0.27, beta = -0.54) after adjusting for diabetes mellitus. In controls, thalamic
      FA and MD values were not related to any cognitive function. CONCLUSION: Our
      findings support the hypothesis that ischemic stroke lesions are associated with
      remote thalamic diffusion abnormalities, and that these abnormalities can
      contribute to cognitive dysfunction 3 months after a cerebrovascular event.

PMID- 24885450
TI  - Diverse attention deficits in patients with neurologically symptomatic and
      asymptomatic Wilson's disease.
AB  - OBJECTIVE: Cognitive deficits in patients with Wilson's disease (WD) have been
      reported in several studies, but there was no detailed analysis of the various
      components of attention, one of the most significant factors of the executive
      system. Our study determined the pattern of deficits in attention subsystems in
      WD patients, including selective attention, divided attention, attention
      switching, and sustained attention. METHOD: We examined 67 WD patients using the
      Test of Everyday Attention (TEA)-33 participants with neurological symptoms and
      34 who were neurologically asymptomatic, but most with mild hepatic dysfunctions.
      The results were compared with 43 matched healthy controls. RESULTS: The group of
      WD patients with neurological symptoms performed significantly worse (p < .05) in
      all components of attention: sustained attention, selective attention, divided
      attention, and attentional switching. WD patients without neurological symptoms
      exhibited significantly lower results in one component-sustained attention (p <
      .05). None of the TEA subtests scores were associated significantly with Unified
      Wilson's Disease Rating Scale scores, which may reflect that the cognitive and
      neurological consequences of WD are relatively independent. CONCLUSIONS: We found
      a deficiency in all components of attention in neurological WD patients. The most
      frequently disturbed function was attention switching. Relatively milder deficits
      concerned divided, selective, and sustained attention. These are all abilities
      creating the core of the executive system and are regulated by subcortical
      prefrontal circuits, which are usually dysfunctional in WD patients. In
      neurologically asymptomatic patients, an isolated deficit of sustained attention
      occurs; this may be a sign of mild hepatic encephalopathy.

PMID- 24885452
TI  - Inhibition of return is not impaired but masked by increased facilitation in
      schizophrenia patients.
AB  - OBJECTIVE: When attention is attracted to an irrelevant location, performance on
      a subsequent target is hindered at that location in relation to novel, not
      previously attended, locations. This phenomenon is known as inhibition of return
      (IOR). Previous research has shown that IOR is not observed, or its onset is
      delayed, in schizophrenia patients. In the present study, the authors tested the
      hypothesis that IOR may be intact but masked by increased facilitation in
      schizophrenia patients. To test this hypothesis, they used a procedure that
      usually reduces or eliminates the early facilitation. METHOD: In the first
      experiment, the authors used the typical single-cue IOR task in the group of
      healthy adults (N = 28) and in a group of schizophrenia patients (N = 32). In the
      second experiment, they manipulated cue-target discriminability by presenting
      spatially overlapping cues and targets where the cues were more intense than the
      targets. RESULTS: In Experiment 1, they did not find significant IOR effects in
      the group of schizophrenia patients, even with cue-target intervals as long as
      3,200 ms. However, in Experiment 2, IOR effects were significant at the 350- and
      450-ms cue-target intervals for healthy and patients, respectively. CONCLUSIONS:
      This is the first study that shows that schizophrenia patients can actually show
      inhibitory effects very similar to healthy controls, even when no help is
      provided to shift their attention away from the irrelevant location. The authors
      suggest that inhibition is intact in schizophrenia patients, but it is usually
      masked by increased facilitation.

PMID- 24885451
TI  - Ten-year longitudinal trajectories of older adults' basic and everyday cognitive
      abilities.
AB  - OBJECTIVE: To examine the longitudinal trajectories of everyday cognition and
      longitudinal associations with basic (i.e., laboratory and experimentally
      measured) cognitive abilities, including verbal memory, inductive reasoning,
      visual processing speed, and vocabulary. METHOD: Participants were healthy older
      adults drawn from the no-treatment control group (N = 698) of the Advanced
      Cognitive Training for the Independent and Vital Elderly (Willis et al., 2006)
      randomized trial and were assessed at baseline and 1, 2, 3, 5, and 10 years
      later. Analyses were conducted using latent growth models. RESULTS: Modeling
      revealed an overall inverted-U shape (quadratic) trajectory across cognitive
      domains. Among basic cognitive predictors, level and slope in reasoning
      demonstrated the closest association to level and slope of everyday cognition,
      and accounted for most of the individual differences in linear gain in everyday
      cognition. CONCLUSION: Everyday cognition is not buffered against decline, and is
      most closely related to inductive reasoning in healthy older adults. To establish
      the clinical utility of everyday cognitive measures, future research should
      examine these associations in samples with more cognitive impairment.

PMID- 24885453
TI  - Estimating age-based antiretroviral therapy costs for HIV-infected children in
      resource-limited settings based on World Health Organization weight-based dosing
      recommendations.
AB  - BACKGROUND: Pediatric antiretroviral therapy (ART) has been shown to
      substantially reduce morbidity and mortality in HIV-infected infants and
      children. To accurately project program costs, analysts need accurate estimations
      of antiretroviral drug (ARV) costs for children. However, the costing of
      pediatric antiretroviral therapy is complicated by weight-based dosing
      recommendations which change as children grow. METHODS: We developed a step-by
      step methodology for estimating the cost of pediatric ARV regimens for children
      ages 0-13 years old. The costing approach incorporates weight-based dosing
      recommendations to provide estimated ARV doses throughout childhood development.
      Published unit drug costs are then used to calculate average monthly drug costs.
      We compared our derived monthly ARV costs to published estimates to assess the
      accuracy of our methodology. RESULTS: The estimates of monthly ARV costs are
      provided for six commonly used first-line pediatric ARV regimens, considering
      three possible care scenarios. The costs derived in our analysis for children
      were fairly comparable to or slightly higher than available published ARV drug or
      regimen estimates. CONCLUSIONS: The methodology described here can be used to
      provide an accurate estimation of pediatric ARV regimen costs for cost
      effectiveness analysts to project the optimum packages of care for HIV-infected
      children, as well as for program administrators and budget analysts who wish to
      assess the feasibility of increasing pediatric ART availability in constrained
      budget environments.

PMID- 24885454
TI  - Task-shifting and prioritization: a situational analysis examining the role and
      experiences of community health workers in Malawi.
AB  - BACKGROUND: As low- and middle-income countries face continued shortages of human
      resources for health and the double burden of infectious and chronic diseases,
      there is renewed international interest in the potential for community health
      workers to assume a growing role in strengthening health systems. A growing list
      of tasks, some of them complex, is being shifted to community health workers' job
      descriptions. Health Surveillance Assistants (HSAs) - as the community health
      worker cadre in Malawi is known - play a vital role in providing essential health
      services and connecting the community with the formal health care sector. The
      objective of this study was to understand the performed versus documented roles
      of the HSAs, to examine how tasks were prioritized, and to understand HSAs'
      perspectives on their roles and responsibilities. METHODS: A situational analysis
      of the HSA cadre and its contribution to the delivery of health services in Zomba
      district, Malawi was conducted. Focus groups and interviews were conducted with
      70 HSAs. Observations of three HSAs performing duties and work diaries from five
      HSAs were collected. Lastly, six policy-maker and seven HSA supervisor interviews
      and a document review were used to further understand the cadre's role and to
      triangulate collected data. RESULTS: HSAs performed a variety of tasks in
      addition to those outlined in the job description resulting in issues of
      overloading, specialization and competing demands existing in the context of task
      shifting and prioritization. Not all HSAs were resistant to the expansion of
      their role despite role confusion and HSAs feeling they lacked adequate training,
      remuneration and supervision. HSAs also said that increasing workload was making
      completing their primary duties challenging. Considerations for policy-makers
      include the division of roles of HSAs in prevention versus curative care;
      community versus centre-based activities; and the potential specialization of
      HSAs. CONCLUSION: This study provides insights into HSAs' perceptions of their
      work, their expanding role and their willingness to change the scope of their
      practice. There are clear decision points for policy-makers regarding future
      direction in policy and planning in order to maximize the cadre's effectiveness
      in addressing the country's health priorities.

PMID- 24885455
TI  - Regulation of ubiquitin-proteasome and autophagy pathways after acute LPS and
      epoxomicin administration in mice.
AB  - BACKGROUND: The ubiquitin-proteasome pathway (UPP) is a major protein degradation
      pathway that is activated during sepsis and has been proposed as a therapeutic
      target for preventing skeletal muscle loss due to cachexia. Although several
      studies have investigated the modulation of proteasome activity in response to
      LPS administration, none have characterized the overall UPP response to LPS
      administration in the fate of proteasome inhibition. METHODS: Here, we determined
      the modulation pattern of the main key components of the UPP in the gastrocnemius
      (GAS) of mice during the acute phase of lipopolysaccharide (LPS)-mediated
      endotoxemia (7.5 mg/kg - 8 h) by measuring all three beta1, beta2 and beta5
      activites of the 20S and 26S proteasomes, the levels of steady state
      polyubiquitinated proteins, mRNA levels of muscle ligases, as well as signaling
      pathways regulating the UPP. Another goal was to assess the effects of
      administration of a specific proteasome inhibitor (epoxomicin, 0.5 mg/kg) on UPP
      response to sepsis. RESULTS: The acute phase of LPS-induced endotoxemia lowered
      GAS/body weight ratio and increased MuRF1 and MAFbx mRNA concomitantly to an
      activation of the pathways known to regulate their expression. Unexpectedly, we
      observed a decrease in all 20S and 26S proteasome activities measured in GAS,
      which might be related to oxidative stress, as oxidized proteins (carbonyl
      levels) increase with LPS. While significantly inhibiting 20S and 26S proteasome
      beta5 activities in heart and liver, epoxomicin did not lower proteasome activity
      in GAS. However, the increase in mRNA expression of the muscle ligases MuRF1 and
      MAFbx were partially rescued without affecting the other investigated signaling
      pathways. LPS also strongly activated autophagy, which could explain the observed
      GAS atrophy with LPS-induced reduction of proteasome activity. CONCLUSIONS: Our
      results highlight an opposite regulation of UPP in the early hours of LPS-induced
      muscle atrophy by showing reduced proteasome activities and increased mRNA
      expression of muscle specific ligases. Furthermore, our data do not support any
      preventive effect of epoxomicin in muscle atrophy due to acute cachexia since
      proteasome activities are not further repressed.

PMID- 24885457
TI  - A linear programming model for preserving privacy when disclosing patient spatial
      information for secondary purposes.
AB  - BACKGROUND: A linear programming (LP) model was proposed to create de-identified
      data sets that maximally include spatial detail (e.g., geocodes such as ZIP or
      postal codes, census blocks, and locations on maps) while complying with the
      HIPAA Privacy Rule's Expert Determination method, i.e., ensuring that the risk of
      re-identification is very small. The LP model determines the transition
      probability from an original location of a patient to a new randomized location.
      However, it has a limitation for the cases of areas with a small population
      (e.g., median of 10 people in a ZIP code). METHODS: We extend the previous LP
      model to accommodate the cases of a smaller population in some locations, while
      creating de-identified patient spatial data sets which ensure the risk of re
      identification is very small. RESULTS: Our LP model was applied to a data set of
      11,740 postal codes in the City of Ottawa, Canada. On this data set we
      demonstrated the limitations of the previous LP model, in that it produces
      improbable results, and showed how our extensions to deal with small areas allows
      the de-identification of the whole data set. CONCLUSIONS: The LP model described
      in this study can be used to de-identify geospatial information for areas with
      small populations with minimal distortion to postal codes. Our LP model can be
      extended to include other information, such as age and gender.

PMID- 24885456
TI  - Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF
      kappaB-dependent MMP-9 expression in MCF-7 breast cancer cells.
AB  - BACKGROUND: Saussurea lappa (SL) has been used as a traditional herbal medicine
      to treat abdominal pain and tenesmus, and has been suggested to possess various
      biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti
      viral, and cardiotonic activities. The effect of SL on breast cancer metastasis,
      however, is unknown. Cell migration and invasion are crucial in neoplastic
      metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular
      matrix, is a major component in cancer cell invasion. METHODS: Cell viability was
      examined by MTT assay, whereas cell motility was measured by invasion assay.
      Western blot, Real-time PCR, and Zymography assays were used to investigate the
      inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level
      in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF
      kappaB in MCF-7 cells. RESULTS: Cells threated with various concentrations of
      Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 MUM did not lead to a
      significant change in cell viability or morphology. Therefore, subsequent
      experiments utilized the optimal non-toxic concentration (2 or 4 MUM) of ESL. In
      this study, we investigated the inhibitory effect of ethanol extract of ESL on
      MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of
      nuclear factor-kappa B (NF-kappaB). However, this result obtained that ESL did
      not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK.
      Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell
      invasion involves the suppression of NF-kB pathway in MCF-7 cells. CONCLUSIONS:
      These results indicate that ELS-mediated inhibition of TPA-induced MMP-9
      expression and cell invasion involves the suppression of NF-kB pathway in MCF-7
      cells. Thus, ESL has potential for controlling breast cancer invasiveness in
      vitro.

PMID- 24885459
TI  - Functionalization of graphene grown on metal substrate with atomic oxygen:
      enolate vs epoxide.
AB  - Graphene functionalization is of great importance in applying graphene as a
      component in functional devices or in activating it for use as a catalyst. Here
      we reveal that atomic oxidation of epitaxial graphene grown on a metal substrate
      results in the formation of enolate, i.e., adsorption of atomic oxygen at the on
      top position, on the basal plane of a graphene, using periodic density functional
      theory calculations. This is striking because the enolate corresponds to the
      transition state between the epoxides on free-standing graphene and on graphite.
      Improved interfacial interaction between graphene and the metal substrate during
      atomic oxidation makes the graphene enolate a local minimum and further highly
      stabilizes it over the graphene epoxide. Our results provide not only a novel
      perspective for a chemical route to functionalizing graphene but also a new
      opportunity to utilize graphene enolate for graphene-based applications. 

PMID- 24885458
TI  - Geographical distribution, a risk factor for the incidence of lupus nephritis in
      China.
AB  - BACKGROUND: Geographical variation in lupus nephritis epidemiology may indicate
      important environmental factors contributions to the etiology of lupus nephritis.
      This paper first describes the epidemiology of biopsy-proven lupus nephritis in
      China by performing a systematic literature review and the possible social
      environmental influential factors. METHODS: The keywords "lupus nephritis",
      "renal biopsy" and "systemic lupus erythematous" were searched in the three
      largest Chinese electronic databases and Medline/PubMed. The data of the patients
      with biopsy-proven lupus nephritis were extracted. The possible environmental
      influential factors including the population density, ethnic group populations,
      the ratio of females to males, the average sunshine per year, annual average
      temperature and annual relative humidity, in different regions of China were
      analyzed. RESULTS: Forty-one study centers with 34574 renal disease patients, and
      3699 lupus nephritis patients met the inclusion criteria. Lupus nephritis
      accounts for 2.37% to 25% of all renal disease and 27.2% to 80.65% of renal
      disease associated with secondary glomerular diseases. The male-to-female ratio
      is approximately 1:5 in lupus nephritis patients. The included period is
      predominantly from 1995 to 2010. The proportion ratio of biopsy-proven lupus
      nephritis in all renal disease or in secondary glomerular disease significantly
      increased with decreasing latitude from the north to the south part of China. The
      population is predominantly Han Chinese. CONCLUSIONS: Geographical distribution
      appears to be a risk factor for the incidence of biopsy-proven LN in China.

PMID- 24885460
TI  - New grading system for upper urinary tract dilation using magnetic resonance
      urography in patients with neurogenic bladder.
AB  - BACKGROUND: In patients with neurogenic bladder (NB), elevated intravesical
      pressures can be transmitted to the upper urinary tract, causing hydronephrosis
      (HN) and ureteral dilation (UD), which are referred to as upper urinary tract
      dilation (UUTD). Ureteral obstruction at the bladder wall is another cause for
      UUTD, but is less of a concern. UUTD can lead to chronic renal failure.
      Therefore, evaluation and protection of UUT function is extremely important in
      the management for NB. Currently, the most common method by which to detect HN
      and UD is ultrasonography (US). The Society for Fetal Urology (SFU) established
      an US HN grading system in 1993, but this system was found to have some defects.
      The purpose of this study is to describe a new grading system for UUTD, including
      both HN and UD, based on magnetic resonance urography (MRU) and to correlate the
      new grading system with the SFU grading system for HN. METHODS: A retrospective
      review of 70 patients with unilateral or bilateral UUTD was completed. Ninety
      five sides in patients with UUTD were graded by the MRU-UUTD and SFU-HN grading
      systems. The results from the two grading systems were compared for each UUTD.
      RESULTS: The MRU-UUTD grading system revealed the following percentages for each
      grade: grade 0, 0; 1, 10.5%; 2, 19%; 3, 42.1%; and 4, 28.4%. The SFU-HN grading
      system revealed the following percentages for each grade: 0, 0; 1, 10.5%; 2, 19%;
      3, 36.8%; and 4, 33.7%. There was no significant systematic difference between
      the two grading systems (p > 0.05), but a significant difference between grades 3
      and 4 (p < 0.05). CONCLUSIONS: The MRU-UUTD grading system correlates well with
      SFU-HN grade, provides an objective and comprehensive evaluation for UUTD, and
      can be used for longitudinal monitoring of UUTD. This new grading system allows
      for better informed clinical decision-making, identifying changes in UUTD.

PMID- 24885461
TI  - The Midland and North of England Stillbirth Study (MiNESS).
AB  - BACKGROUND: The United Kingdom has one of the highest rates of stillbirth in
      Europe, resulting in approximately 4,000 stillbirths every year. Potentially
      modifiable risk factors for late stillbirths are maternal age, obesity and
      smoking, but the population attributable risk associated with these risk factors
      is small.Recently the Auckland Stillbirth Study reported that maternal sleep
      position was associated with late stillbirth. Women who did not sleep on their
      left side on the night before the death of the baby had double the risk compared
      with sleeping on other positions. The population attributable risk was 37%. This
      novel observation needs to be replicated or refuted. METHODS/DESIGN: Case control
      study of late singleton stillbirths without congenital abnormality. Controls are
      women with an ongoing singleton pregnancy, who are randomly selected from
      participating maternity units booking list of pregnant women, they are allocated
      a gestation for interview based on the distribution of gestations of stillbirths
      from the previous 4 years for the unit. The number of controls selected is
      proportional to the number of stillbirths that occurred at the hospital over the
      previous 4 years. DATA COLLECTION: Interviewer administered questionnaire and
      data extracted from medical records. SAMPLE SIZE: 415 cases and 830 controls.
      This takes into account a 30% non-participation rate, and will detect an OR of
      1.5 with a significance level of 0.05 and power of 80% for variables with a
      prevalence of 57%, such as non-left sleeping position. STATISTICAL ANALYSIS:
      Mantel-Haenszel odds ratios and unconditional logistic regression to adjust for
      potential confounders. DISCUSSION: The hypotheses to be tested here are
      important, biologically plausible and amenable to a public health intervention.
      Although this case-control study cannot prove causation, there is a striking
      parallel with research relating to sudden infant death syndrome, where case
      control studies identified prone sleeping position as a major modifiable risk
      factor. Subsequently mothers were advised to sleep babies prone ("Back to Sleep"
      campaign), which resulted in a dramatic drop in SIDS. This study will provide
      robust evidence to help determine whether such a public health intervention
      should be considered. TRIAL REGISTRATION NUMBER: NCT02025530.

PMID- 24885463
TI  - Association between risk of oral precancer and genetic variations in microRNA and
      related processing genes.
AB  - BACKGROUND: MicroRNAs have been implicated in cancer but studies on their role in
      precancer, such as leukoplakia, are limited. Sequence variations at eight miRNA
      and four miRNA processing genes were studied in 452 healthy controls and 299
      leukoplakia patients to estimate risk of disease. RESULTS: Genotyping by TaqMan
      assay followed by statistical analyses showed that variant genotypes at Gemin3
      and mir-34b reduced risk of disease [OR = 0.5(0.3-0.9) and OR = 0.7(0.5-0.9)
      respectively] in overall patients as well as in smokers [OR = 0.58(0.3-1) and OR
      = 0.68(0.5-0.9) respectively]. Among chewers, only mir29a significantly increased
      risk of disease [OR = 1.8(1-3)]. Gene-environment interactions using MDR-pt
      program revealed that mir29a, mir34b, mir423 and Xpo5 modulated risk of disease
      (p < 0.002) which may be related to change in expression of these genes as
      observed by Real-Time PCR assays. But association between polymorphisms and gene
      expressions was not found in our sample set as well as in larger datasets from
      open access platforms like Genevar and 1000 Genome database. CONCLUSION:
      Variations in microRNAs and their processing genes modulated risk of precancer
      but further in-depth study is needed to understand mechanism of disease process.

PMID- 24885464
TI  - Behavioural factors associated with diarrhea among adults over 18 years of age in
      Beijing, China.
AB  - BACKGROUND: To date, a large proportion of people still suffer from diarrhea
      diseases. In addition to the burden of diarrhea, there are substantial social and
      economic costs caused by the high incidence of diarrheal diseases. Therefore, the
      purpose of this study was to explore the self-reported prevalence of diarrhea and
      associated risk factors of diarrhea among adults in Beijing, China. METHODS: A
      multistage, stratified study based on cross-sectional data was performed using
      randomized and systematic sampling, recruiting 12,936 adults over 18 years of age
      in Beijing. All adults were requested to complete a questionnaire, including
      information such as demographic characteristics, incidence of diarrhea, and
      behaviors related to the diarrhea. RESULTS: The self-reported prevalence of
      diarrhea was 17.5% during the last year prior to the survey. Six behavioral
      factors were significantly associated with diarrhea in our study including: (1)
      washing hands before meals and after defecation (Adjusted Odds Ratio (AOR) 0.707,
      95% CI 0.597 ~ 0.837), (2) washing hands with soap and running water (AOR 0.872,
      95% CI 0.786 ~ 0.967), (3) consuming raw seafood (AOR 1.285, 95% CI 1.138 ~
      1.450), (4) using the same chopping block and knife when processing raw and
      cooked food (AOR 1.375, 95% CI 1.225 ~ 1.542), (5) using the same chopsticks to
      handle raw and cooked food (AOR1.149, 95% CI 1.041 ~ 1.268), and (6) regularly
      participating in physical exercise (AOR 0.719, 95% CI 0.651 ~ 0.793). CONCLUSION:
      Good health habits, good eating habits, and regular exercise can prevent the
      episodes of diarrhea, and thus decrease the potential for disease occurrence.

PMID- 24885462
TI  - Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS
      era.
AB  - BACKGROUND: Genome-scale studies of psoriasis have been used to identify genes of
      potential relevance to disease mechanisms. For many identified genes, however,
      the cell type mediating disease activity is uncertain, which has limited our
      ability to design gene functional studies based on genomic findings. METHODS: We
      identified differentially expressed genes (DEGs) with altered expression in
      psoriasis lesions (n = 216 patients), as well as candidate genes near
      susceptibility loci from psoriasis GWAS studies. These gene sets were
      characterized based upon their expression across 10 cell types present in
      psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding)
      loci was evaluated to identify sites of allele-specific transcription factor
      binding. RESULTS: Half of DEGs showed highest expression in skin cells, although
      the dominant cell type differed between psoriasis-increased DEGs (keratinocytes,
      35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS
      candidates tended to have highest expression in immune cells (71%), with a
      significant fraction showing maximal expression in neutrophils (24%, P < 0.001).
      By identifying candidate cell types for genes near susceptibility loci, we could
      identify and prioritize SNPs at which susceptibility variants are predicted to
      influence transcription factor binding. This led to the identification of
      potentially causal (non-coding) SNPs for which susceptibility variants influence
      binding of AP-1, NF-kappaB, IRF1, STAT3 and STAT4. CONCLUSIONS: These findings
      underscore the role of innate immunity in psoriasis and highlight neutrophils as
      a cell type linked with pathogenetic mechanisms. Assignment of candidate cell
      types to genes emerging from GWAS studies provides a first step towards
      functional analysis, and we have proposed an approach for generating hypotheses
      to explain GWAS hits at intergenic loci.

PMID- 24885465
TI  - What do women with gynecologic cancer know about HPV and their individual
      disease? A pilot study.
AB  - BACKGROUND: The vaccinations against human papilloma virus (HPV) are highly
      effective in preventing persistent infection. The level of knowledge about HPV
      and the consequences of an infection with this virus are low in the general
      population and in patients who suffer from HPV-associated diseases. We aimed to
      compare the level of knowledge about HPV and about the women's individual
      malignant disease between women with and without HPV-associated gynecologic
      cancer as well as the knowledge about individual malignant diseases. METHODS: In
      a pilot study, 51 women with HPV-related cancer (cervical cancer: n=30; vulvar or
      vaginal cancer: n=21) and 60 women with non-HPV associated gynecologic
      malignancies (ovarian cancer: n=30; endometrial cancer, n=30) were included. They
      answered a questionnaire including questions about personal medical history, risk
      factors for cancer development, and HPV. RESULTS: The general level of knowledge
      of the term "HPV" was low (29.7%, 33/111) and it was similar in patients with HPV
      related and non-HPV-associated cancer (18/60, 30.0% vs. 15/51, 29.4%,
      respectively; p=1.000). When asked about their disease, 80% (24/30) of women with
      ovarian cancer correctly named their diagnosis, followed by women with cervical
      cancer (73.3%, 22/30), endometrial cancer (70%, 21/30) and vaginal or vulvar
      cancer (42.9%, 9/21; p=0.008). CONCLUSION: The level of knowledge about HPV and
      the malignant diseases the patient suffered from was low. This applied even to
      patients with HPV associated malignancies.

PMID- 24885466
TI  - Absence of antibodies to Rickettsia spp., Bartonella spp., Ehrlichia spp. and
      Coxiella burnetii in Tahiti, French Polynesia.
AB  - BACKGROUND: In the Pacific islands countries and territories, very little is
      known about the incidence of infectious diseases due to zoonotic pathogens. To
      our knowledge, human infections due to Rickettsia spp., Coxiella burnetii,
      Ehrlichia spp. and Bartonella spp. have never been reported in French Polynesia;
      and infections due to C. burnetti have been reported worldwide except in New
      Zealand. To evaluate the prevalence of this disease, we conducted a serosurvey
      among French Polynesian blood donors. METHODS: The presence of immunoglobulin G
      antibodies against R. felis, R. typhi, R. conorii, C. burnetii, B. henselae, B.
      quintana, and E. chaffeensis was evaluated by indirect immunofluorescence assay
      in sera from 472 French Polynesian blood donors collected from 2011 to 2013. In
      addition, 178 ticks and 36 cat fleas collected in French Polynesia were also
      collected and tested by polymerase chain reaction to detect Rickettsia spp., B.
      henselae and Ehrlichia spp. RESULTS: None of the blood donors had antibodies at a
      significant level against Rickettsia spp., Coxiella burnetii, Ehrlichia spp. and
      Bartonella spp. All tested ticks and cat fleas were PCR-negative for Rickettsia
      spp., B. henselae, and Ehrlichia spp. CONCLUSION: We cannot conclude that these
      pathogens are absent in French Polynesia but, if present, their prevalence is
      probably very low. C. burnetii has been reported worldwide except in New Zealand.
      It may also be absent from French Polynesia.

PMID- 24885467
TI  - Substrate dependent in vitro antifungal activity of Bacillus sp strain AR2.
AB  - BACKGROUND: Biosurfactants are a structurally diverse group of secondary
      metabolites with lots of potential to serve mankind. Depending upon the structure
      and composition they may exhibit properties that make them suitable for a
      particular application. Structural and compositional diversity of biosurfactant
      is unambiguously substrate dependent. The present study investigates the
      qualitative and quantitative effect of different water soluble carbon source on
      the biosurfactant produced by Bacillus amylofaciens strain AR2. RESULTS: Strain
      AR2 produced lipopeptide type biosurfactant while growing on water soluble carbon
      sources. Maximum biosurfactant production was observed in the sucrose
      supplemented minimal salt medium (MSM). Strain AR2 exhibited carbon source
      dependent surface tension reduction in the range of 30-37 mN/m, critical micelle
      concentration (CMC) in the range 80-110 mg/l and emulsification index (EI24
      kerosene) in the range of 32-66%. In dextrose, sucrose and glycerol supplemented
      MSM, strain AR2 produced lipopeptides as a mixture of surfactin, iturin and
      fengycin. However, in the presence of maltose, lactose and sorbitol only iturin
      was produced. This substrate dependent compositional variation in the
      lipopeptides significantly influenced antifungal activity. Lipopeptides produced
      by strain AR2 while growing on sucrose and dextrose based MSM was observed to be
      most efficient as an antifungal agent. CONCLUSIONS: These results suggest that
      carbon source provided for the growth and biosurfactant production not only
      influences the yield but also the type of biosurfactant. Sucrose is the most
      suitable carbon source for production of lipopeptide biosurfactant with
      antifungal activity.

PMID- 24885468
TI  - Characteristics of activities that affect the development of women's same-sex
      relationships.
AB  - The author utilized semistructured interviews with 56 women to explore how a wide
      range of activities affected the development of the participants' same-sex
      attractions and relationships. The researcher was able to identify and describe
      some aspects of the process by which eight characteristics of activities that are
      more or less present in various social contexts have the potential to impact
      whether these contexts are more or less conducive or hindering to the development
      of women's same-sex attractions and relationships. Activities were more apt to
      nurture the development of the participants' same-sex attractions and
      relationships when the activity (a) included lesbians, (b) was composed primarily
      of women, (c) affirmed women, (d) facilitated bonding, (e) featured a climate of
      acceptance of lesbians/gays/bisexuals, (f) did not feature a climate that
      emphasized heteronormativity, (g) was perceived as gender neutral, and (h)
      generated or drew participants who were similar to each other. 

PMID- 24885470
TI  - Effect of Fe nanoparticle on growth and glycolipid biosurfactant production under
      solid state culture by marine Nocardiopsis sp. MSA13A.
AB  - BACKGROUND: Iron is an essential element in several pathways of microbial
      metabolism, and therefore low iron toxicity is expected on the usage of Fe
      nanoparticles (NPs). This study aims to determine the effect of Fe NPs on
      biosurfactant production by marine actinobacterium Nocardiopsis sp. MSA13A under
      solid state culture. Foam method was used in the production of Fe NPs which were
      long and fiber shaped in nature. RESULTS: The SEM observation showed non toxic
      nature of Fe NPs as no change in the morphology of the filamentous structure of
      Nocardiopsis MSA13A. The production of biosurfactant by Nocardiopsis MSA13A under
      solid state culture supplemented with Fe NPs increased to 80% over control. The
      biosurfactant produced by Nocardiopsis MSA13A was characterized as glycolipid
      derivative which effectively disrupted the pre-formed biofilm of Vibrio pathogen.
      CONCLUSION: The use of metal NPs as supplement would reduce the impact of non
      metallic ions of the metal salts in a fermentation process. This would ultimately
      useful to achieve greener production process for biosurfactants. The present
      results are first report on the optimization of biosurfactant production under
      SSC using Fe NPs.

PMID- 24885471
TI  - Encounters with fierce dogs and itchy bedbugs: why my first field work failed.
AB  - This essay, which is the fifth in the series "Recollections, Reflections, and
      Revelations: Personal Experiences in Ethnobiology", is a personal reminiscence by
      the researcher on his first field experience in Turkey in the late 1970s, which
      was a failure from an ethnobiological point of view but a success for a social
      scientist pursuing Turkic studies. The author later returned to ethnobiology
      during subsequent fieldwork on the Faroes. 

PMID- 24885469
TI  - Matrix metalloproteinase 12 is induced by heterogeneous nuclear ribonucleoprotein
      K and promotes migration and invasion in nasopharyngeal carcinoma.
AB  - BACKGROUND: Overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP
      K), a DNA/RNA binding protein, is associated with metastasis in nasopharyngeal
      carcinoma (NPC). However, the mechanisms underlying hnRNP K-mediated metastasis
      is unclear. The aim of the present study was to determine the role of matrix
      metalloproteinase (MMP) in hnRNP K-mediated metastasis in NPC. METHODS: We
      studied hnRNP K-regulated MMPs by analyzing the expression profiles of MMP family
      genes in NPC tissues and hnRNP K-knockdown NPC cells using Affymetrix microarray
      analysis and quantitative RT-PCR. The association of hnRNP K and MMP12 expression
      in 82 clinically proven NPC cases was determined by immunohistochemical analysis.
      The hnRNP K-mediated MMP12 regulation was determined by zymography and Western
      blot, as well as by promoter, DNA pull-down and chromatin immunoprecipitation
      (ChIP) assays. The functional role of MMP12 in cell migration and invasion was
      demonstrated by MMP12-knockdown and the treatment of MMP12-specific inhibitor, PF
      356231. RESULTS: MMP12 was overexpressed in NPC tissues, and this high level of
      expression was significantly correlated with high-level expression of hnRNP K (P
      = 0.026). The levels of mRNA, protein and enzyme activity of MMP12 were reduced
      in hnRNP K-knockdown NPC cells. HnRNP K interacting with the region spanning -42
      to -33 bp of the transcription start site triggered transcriptional activation of
      the MMP12 promoter. Furthermore, inhibiting MMP12 by MMP12 knockdown and MMP12
      specific inhibitor, PF-356231, significantly reduced the migration and invasion
      of NPC cells. CONCLUSIONS: Overexpression of MMP12 was significantly correlated
      with hnRNP K in NPC tissues. HnRNP K can induce MMP12 expression and enzyme
      activity through activating MMP12 promoter, which promotes cell migration and
      invasion in NPC cells. In vitro experiments suggest that NPC metastasis with high
      MMP12 expression may be treated with PF-356231. HnRNP K and MMP12 may be
      potential therapeutic markers for NPC, but additional validation studies are
      warranted.

PMID- 24885472
TI  - NF-kappaB-modulated miR-130a targets TNF-alpha in cervical cancer cells.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) induces a variety of biological
      processes through transcriptional gene control whose products are components in
      various signaling pathways. MicroRNAs are a small endogenous non-coding RNAs that
      regulate gene expression and are involved in tumorigenesis. Using human cervical
      cancer cell lines, this study aimed to investigate whether NF-kappaB could
      regulate miR-130a expression and the functions and targets of miR-130a. METHODS:
      We used the HeLa and C33A cervical cancer cell lines that were transfected with
      NF-kappaB or miR-130a overexpression plasmids to evaluate their effects on cell
      growth. We utilized bioinformatics, a fluorescent reporter assay, qRT-PCR and
      Western blotting to identify downstream target genes. RESULTS: In HeLa and C33A
      cells, NF-kappaB and miR-130a overexpression promoted cell growth, but genetic
      knockdowns suppressed growth. TNF-alpha was identified as a target of miR-130a by
      binding in a 3'-untranslated region (3'UTR) EGFP reporter assay and by Western
      blot analysis. Furthermore, low TNF-alpha concentrations stimulated NF-kappaB
      activity and then induced miR-130a expression, and TNF-alpha overexpression
      rescued the effects of miR-130a on cervical cancer cells. CONCLUSIONS: Our
      findings indicate that TNF-alpha can activate NF-kappaB activity, which can
      reduce miR-130a expression, and that miR-130a targets and downregulates TNF-alpha
      expression. Hence, we shed light on the negative feedback regulation of NF
      kappaB/miR-130a/TNF-alpha/NF-kappaB in cervical cancer and may provide insight
      into the carcinogenesis of cervical cancer.

PMID- 24885473
TI  - Reliability and validity of a questionnaire for self-assessment of complete
      dentures.
AB  - BACKGROUND: Demand for complete denture treatment is expected to rise over
      several decades. However, to date, no questionnaire on complete dentures, as
      evaluated by edentulous patients, has been shown to be reliable and valid. This
      study sought to assess the reliability and validity of Patient's Denture
      Assessment (PDA), which provides a multidimensional evaluation of dentures among
      edentulous patients. METHODS: Patients, who had new complete dentures fabricated
      at the University Hospital of Dentistry, Tokyo Medical and Dental University
      through 2009 to 2010, were enrolled. The reliability of the PDA was determined by
      examining internal consistency and test-retest reliability. Internal consistency
      for all of the question items and the six subscales was measured using Cronbach's
      alpha and average inter-item correlation coefficients among 93 participants. For
      33 of these participants, test-retest reliability was determined at a 2 month
      interval using the interclass correlation coefficients (ICCs) and 95% confidence
      interval for the summary scores and the six subscale scores. The PDA was
      validated in 93 participants by examining the difference in the summary score and
      the six subscale scores of the PDA before and after replacement with new dentures
      by the paired t-test. Ability to detect change was also tested in 93 patients
      using effect size. RESULTS: The Cronbach's alpha for the PDA ranged from 0.56 to
      0.93. The average inter-item correlation coefficients ranged from 0.28 to 0.83.
      ICCs for the PDA ranged from 0.37 to 0.83. The paired t-test showed a significant
      difference between the summary score and the six subscale scores before and after
      replacement with new dentures (p < 0.05) and the effect size was 0.97.
      CONCLUSIONS: The PDA demonstrated good reliability by assessing internal
      consistency and test-retest reliability. In addition, the PDA demonstrated good
      validity by assessing discriminant validity. Thus, the PDA could help dentists
      obtain a detailed understanding of the patients' perceptions in using their
      dentures.

PMID- 24885475
TI  - Fluoroethylene carbonate as an important component in electrolyte solutions for
      high-voltage lithium batteries: role of surface chemistry on the cathode.
AB  - The effect of fluorinated ethylene carbonate (FEC) as a cosolvent in alkyl
      carbonates/LiPF6 on the cycling performance of high-voltage (5 V) cathodes for Li
      ion batteries was investigated using electrochemical tools, X-ray photoelectron
      spectroscopy (XPS), and high-resolution scanning electron microscopy (HRSEM). An
      excellent cycling stability of LiCoPO4/Li, LiNi0.5Mn1.5O4/Si, and LiCoPO4/Si
      cells and a reasonable cycling of LiCoPO4/Si cells was achieved by replacing the
      commonly used cosolvent ethylene carbonate (EC) by FEC in electrolyte solutions
      for high-voltage Li-ion batteries. The roles of FEC in the improvement of the
      cycling performance of high-voltage Li-ion cells and of surface chemistry on the
      cathode are discussed. 

PMID- 24885474
TI  - Early intervention in Alzheimer's disease: a health economic study of the effects
      of diagnostic timing.
AB  - BACKGROUND: Intervention and treatment in Alzheimer's disease dementia (AD
      dementia) can be cost effective but the majority of patients are not diagnosed in
      a timely manner. Technology is now available that can enable the earlier
      detection of cognitive loss associated with incipient dementia, offering the
      potential for earlier intervention in the UK health care system. This study aimed
      to determine to what extent the timing of an intervention affects its cost
      effectiveness. METHODS: Using published data describing cognitive decline in the
      years prior to an AD diagnosis, we modelled the effects on healthcare costs and
      quality-adjusted life years of hypothetical symptomatic and disease-modifying
      interventions. Early and standard interventions were assumed to have equal
      clinical effects, but the early intervention could be applied up to eight years
      prior to standard diagnosis. RESULTS: A symptomatic treatment which immediately
      improved cognition by one MMSE point and reduced in efficacy over three years,
      would produce a maximum net benefit when applied at the earliest timepoint
      considered, i.e. eight years prior to standard diagnosis. In this scenario, the
      net benefit was reduced by around 17% for every year that intervention was
      delayed. In contrast, for a disease-modifying intervention which halted cognitive
      decline for one year, economic benefits would peak when treatment effects were
      applied two years prior to standard diagnosis. In these models, the maximum net
      benefit of the disease modifying intervention was fifteen times larger than that
      of the symptomatic treatment. CONCLUSION: Timeliness of intervention is likely to
      have an important impact on the cost-effectiveness of both current and future
      treatments. Healthcare policy should aim to optimise the timing of AD-dementia
      diagnosis, which is likely to necessitate detecting and treating patients several
      years prior to current clinical practice.

PMID- 24885476
TI  - Adoption of workplaces and reach of employees for a multi-faceted intervention
      targeting low back pain among nurses' aides.
AB  - BACKGROUND: Workplace adoption and reach of health promotion are important, but
      generally poorly reported. The aim of this study is therefore to evaluate the
      adoption of workplaces (organizational level) and reach of employees (individual
      level) of a multi-faceted workplace health promotion and work environment
      intervention targeting low back pain among nurses' aides in elderly care.
      METHODS: Percentage of adopters was calculated among eligible workplaces and
      differences between adopters and non-adopters were evaluated through workplace
      registrations and manager questionnaires from all eligible workplaces. From the
      adopted workplaces reach was calculated among eligible employees as the
      percentage who responded on a questionnaire. Responders were compared with non
      responders using data from company registrations. Among responders, comparisons
      based on questionnaire data were performed between those consenting to
      participate in the intervention (consenters) and those not consenting to
      participate in the intervention (non-consenters). Comparisons were done using
      Student's t-test for the continuous variables, Fisher's exact test for
      dichotomous variables and the Pearson's chi(2) for categorical variables.
      Moreover odds ratios for non-responding and non-consenting were investigated with
      binary logistic regression analyses. RESULTS: The project was adopted by 44% of
      the offered workplaces. The main differences between adopters and non-adopters
      were that workplaces adopting the intervention had a more stable organization as
      well as a management with positive beliefs of the intervention's potential
      benefits. Of eligible employees, 71% responded on the questionnaire and 57%
      consented to participate. Non-responders and non-consenters did not differ from
      the responders and consenters on demographic factors and health. However, more
      non-responders and non-consenters were low skilled, worked less than 30 hours pr.
      week, and worked evening and nightshift compared to responders and consenters,
      respectively. Consenters had more musculoskeletal pain and reduced self-rated
      health, as well as higher physical exertion during work compared to non
      consenters. CONCLUSIONS: Our recruitment effort yielded a population of
      consenters that was representative of the target population of nurses' aides with
      respect to demographic factors, and health. Moreover more consenters had problems
      like pain and high physical exertion during work, which fitted the scope of the
      intervention. TRIAL REGISTRATION: The study is registered as ISRCTN78113519.

PMID- 24885477
TI  - Psychometric study of the Persian short-form eight-item Parkinson's disease
      questionnaire (PDQ-8) to evaluate health related quality of life (HRQoL).
AB  - BACKGROUND: To assess validation and reliability of the Persian version of the
      short-form 8-item Parkinson's disease questionnaire (PDQ-8) and to compare its
      psychometric properties with that of the long-form questionnaire (PDQ-39) in
      order to evaluate the health-related quality of life (HRQoL) in patients with
      Parkinson's disease (PD). METHODS: This cross-sectional study was conducted on
      114 non-demented idiopathic PD (IPD) patients consecutively recruited from an
      outpatient referral movement disorder clinic. Patients were interviewed to fill
      in the Persian version of PDQ-39 and PDQ-8 questionnaires and clinical
      examination was performed to measure disease severity indices. RESULTS: The
      Cronbach's alpha coefficient of the entire PDQ-8 was 0.740 (95% CI: 0.661-0.806).
      Replacement of PDQ-8 items with other questions with the highest internal
      consistency within each dimension of the original PDQ-39 did not improve
      Cronbach's alpha coefficient [0.723 (95% CI: 0.639-0.794)]. The scores from both
      PDQ-8 and PDQ-39 had significant correlation with the Hoehn & Yahr (rPDQ-8 =
      0.376, rPDQ-39 = 0.442), and Schwab & England (rPDQ-8 = -0.503, rPDQ-39 = -0.598)
      disease severity scales and disease duration (rPDQ-8 = 0.342, rPDQ-39 = 0.396).
      CONCLUSIONS: Persian version of the short-form PDQ (PDQ-8) was shown to be a
      valid and reliable instrument to assess disease-specific HRQoL in a PD population
      when used independently. Although the PDQ-8 items were not necessarily those with
      the highest internal consistency in the components of PDQ-39, they entirely
      showed proper psychometric properties especially in mental and behavioral
      aspects. PDQ-8 is a practical and informative instrument in daily clinical
      practice where clinicians are in shortage of time and when a validated self
      reported brief questionnaire is of value.

PMID- 24885478
TI  - Latent transforming growth factor-beta1 protects against bleomycin-induced lung
      injury in mice.
AB  - Transforming growth factor (TGF)-beta1 is a potent mediator known to induce lung
      fibrosis. However, the role of latent TGF-beta1 in lung inflammation and fibrosis
      is unclear. To investigate the role of circulating latent TGF-beta1 in bleomycin
      induced lung injury, lung disease was induced in keratin-5 promoter-driven TGF
      beta1(wt) transgenic (Tg) mice by bleomycin. The role of latent TGF-beta1 in
      pulmonary inflammation and fibrosis was examined at Days 7 and 28 after
      administration of bleomycin. Compared with littermate wild-type (WT) mice, TGF
      beta1(wt) Tg mice had over twofold-higher levels of latent TGF-beta1 in both
      plasma and lung tissue, and were protected from bleomycin-induced pulmonary
      inflammation, such as up-regulation of IL-1beta, TNF-alpha, and macrophage
      chemotactic protein-1, and infiltration of CD3(+) T cells and F4/80(+)
      macrophages. In addition, the severity of lung fibrosis with massive collagen
      matrix accumulation was markedly reduced in TGF-beta1(wt) Tg mice. These
      protective effects were associated with higher levels of Smad7 and inactivation
      of both NF-kappaB and TGF-beta/Smad3 signaling pathways, in addition to an
      increase in forkhead box P3 (Foxp3)-dependent regulatory T cells, but inhibition
      of T helper 17-mediated lung injury. In summary, mice overexpressing latent TGF
      beta1 are protected from bleomycin-induced lung injury. Triggering the Smad7
      negative feedback mechanism to inhibit both NF-kappaB and TGF-beta/Smad signaling
      pathways, and enhancing the regulatory T cell response to counter-regulate T
      helper 17-mediated lung injury, are potential mechanisms by which latent TGF
      beta1 protects against bleomycin-induced lung injury. 

PMID- 24885480
TI  - Maternal deaths among rural-urban migrants in China: a case-control study.
AB  - BACKGROUND: Disparity in maternal mortality exists between rural-urban migrant
      and urban resident women in China, but little research has provided evidence for
      related policy development. The objective of this study was to identify
      associations with and risks for maternal death among rural-urban migrant women in
      order to improve health services for migrant women and reduce maternal mortality
      in China. METHODS: We conducted a prospective case-control study in urban areas
      of Guangdong, Zhejiang and Fujian provinces and Beijing municipality. In each,
      migrant women who died between July 1, 2010 and October 1, 2011 were identified
      through reports from China's Maternal and Child Mortality Surveillance System.
      For each, four matched controls were selected from migrant women who delivered in
      local hospitals during the same period. We compared socio-demographic
      characteristics, health status and health service variables between cases and
      controls, and used bivariate and multivariate conditional logistic regression
      analyses to determine associations with and risk factors for maternal death.
      RESULTS: 109 cases and 436 controls were assessed. Family income <2000 yuan per
      month (OR = 4.5; 95% CI 1.7-11.7) and lack of health insurance (OR = 1.3; 95% CI
      1.1-1.6) were more common amongst women who died, as were lack of antenatal care
      (ANC) (OR = 22.3; 95% CI 4.3-116.0) and attending ANC only 1-4 times (OR = 5.0;
      95% CI 1.6-15.5). Knowledge of danger signs during delivery was less common in
      this group (OR = 0.3; 95% CI 0.1-0.8). CONCLUSION: Differences existed between
      migrant women who died in pregnancy and surviving controls. The identified risk
      factors suggest strategies for health sector and community action on reducing
      maternal mortality among migrant women in China. A systematic approach to
      maternity care for rural-urban migrant women is recommended.

PMID- 24885479
TI  - Clinical experience with ipilimumab 3 mg/kg: real-world efficacy and safety data
      from an expanded access programme cohort.
AB  - BACKGROUND: Ipilimumab improves survival in patients with advanced melanoma. The
      activity and safety of ipilimumab outside of a clinical trial was assessed in an
      expanded access programme (EAP). METHODS: Ipilimumab was available upon physician
      request for patients aged 16 or over with pretreated stage III (unresectable)/IV
      melanoma, for whom no other therapeutic option was available. Patients received
      ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or
      an objective response to ipilimumab were eligible for retreatment upon disease
      progression. Tumour assessments were conducted at baseline and week 12. Patients
      were monitored for adverse events (AEs) within 3 to 4 days of each scheduled
      visit. RESULTS: Of 855 patients participating in the EAP in Italy, 833 were
      evaluable for response. Of these, 13% had an objective immune response, and the
      immune-related disease control rate was 34%. Median progression-free survival and
      overall survival were 3.7 and 7.2 months, respectively. Efficacy was independent
      of BRAF and NRAS mutational status. Overall, 33% of patients reported an immune
      related AE (irAE). The frequency of irAEs was not associated with response to
      ipilimumab. CONCLUSIONS: Outside of a clinical trial setting, ipilimumab is a
      feasible treatment option in patients with pretreated metastatic melanoma,
      regardless of BRAF and NRAS mutational status. Data from this large cohort of
      patients support clinical trial evidence that ipilimumab can induce durable
      disease control and long-term survival in patients who have failed to respond to
      prior treatment.

PMID- 24885481
TI  - MicroRNAs define distinct human neuroblastoma cell phenotypes and regulate their
      differentiation and tumorigenicity.
AB  - BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in
      children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell
      lines are classified by phenotype, each having distinct differentiation and
      tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal
      features and includes stem cells (I-cells) and neuronal cells (N-cells). The non
      neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with
      features of glial/smooth muscle precursor cells. This study identified miRNAs
      associated with each distinct cell phenotypes and investigated their role in
      regulating associated differentiation and tumorigenic properties. METHODS: A
      miRNA microarray was performed on the three cell phenotypes and expression
      verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated
      using miRNA inhibitors or stable transfection. Neuronal differentiation was
      induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity
      were assayed by soft agar colony forming ability. N-myc binding to miR-375
      promoter was assayed by chromatin-immunoprecipitation. RESULTS: Unsupervised
      hierarchical clustering of miRNA microarray data segregated neuroblastic and non
      neuronal cell lines and showed that specific miRNAs define each phenotype. qRT
      PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are
      associated with the non-neuronal phenotype, whereas increased levels of miR-124
      and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non
      neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of
      neuronal differentiation. Overexpression of miR-124 in stem cells induces
      terminal neuronal differentiation with reduced malignancy. Expression of miR-375
      is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc.
      Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding
      protein HuD. CONCLUSIONS: Thus, miRNAs define distinct NB cell phenotypes.
      Increased levels of miR-21, miR-221 and miR-335 characterize the non-neuronal,
      non-malignant phenotype and miR-335 maintains the non-neuronal features possibly
      by blocking neuronal differentiation. miR-124 induces terminal neuronal
      differentiation with reduction in malignancy. Data suggest N-myc inhibits
      neuronal differentiation of neuroblastic cells possibly by upregulating miR-375
      which, in turn, suppresses HuD. As tumor differentiation state is highly
      predictive of patient survival, the involvement of these miRNAs with NB
      differentiation and tumorigenic state could be exploited in the development of
      novel therapeutic strategies for this enigmatic childhood cancer.

PMID- 24885482
TI  - Two-dimensional strain-hardening membrane model for large deformation behavior of
      multiple red blood cells in high shear conditions.
AB  - BACKGROUND: Computational modeling of Red Blood Cell (RBC) flow contributes to
      the fundamental understanding of microhemodynamics and microcirculation. In order
      to construct theoretical RBC models, experimental studies on single RBC mechanics
      have presented a material description for RBC membranes based on their membrane
      shear, bending and area moduli. These properties have been directly employed in
      3D continuum models of RBCs but practical flow analysis with 3D models have been
      limited by their computationally expensive nature. As such, various researchers
      have employed 2D models to efficiently and qualitatively study microvessel flows.
      Currently, the representation of RBC dynamics using 2D models is a limited
      methodology that breaks down at high shear rates due to excessive and unrealistic
      stretching. METHODS: We propose a localized scaling of the 2D elastic moduli such
      that it increases with RBC local membrane strain, thereby accounting for effects
      such as the Poisson effect and membrane local area incompressibility lost in the
      2D simplification. Validation of our 2D Large Deformation (2D-LD) RBC model was
      achieved by comparing the predicted RBC deformation against the 3D model from
      literature for the case of a single RBC in simple shear flow under various shear
      rates (dimensionless shear rate G = 0.05, 0.1, 0.2, 0.5). The multi-cell flow of
      RBCs (38% Hematocrit) in a 20 MUm width microchannel under varying shear rates
      (50, 150, 150 s-1) was then simulated with our proposed model and the popularly
      employed 2D neo-Hookean model in order to evaluate the efficacy of our proposed
      2D-LD model. RESULTS: The validation set indicated similar RBC deformation for
      both the 2D-LD and the 3D models across the studied shear rates, highlighting the
      robustness of our model. The multi-cell simulation indicated that the 2D neo
      Hookean model predicts noodle-like RBC shapes at high shear rates (G = 0.5)
      whereas our 2D-LD model maintains sensible RBC deformations. CONCLUSION: The
      ability of the 2D-LD model to limit RBC strain even at high shear rates enables
      this proposed model to be employed in practical simulations of high shear rate
      microfluidic flows such as blood separation channels.

PMID- 24885483
TI  - Neck swelling from a retropharyngeal abscess caused by penicillin-resistant
      Streptococcus pneumoniae: a case report.
AB  - BACKGROUND: In small children, retropharyngeal abscesses usually occur after
      upper respiratory tract infections. Unlike in adults, these abscesses are
      difficult to diagnose in small children, and can rapidly develop into deep neck
      or mediastinal abscesses. CASE PRESENTATION: A 2-year-old Japanese boy recently
      presented to our department with a chief complaint of neck swelling. Physical
      examination revealed bilateral tonsillitis and swelling of the left posterior
      pharyngeal wall. Emergency neck computed tomography angiography showed a contrast
      enhanced abscess cavity posterior to the left retropharyngeal space, and a low
      density area surrounded by an area without contrast enhancement in the posterior
      neck. The latter was suspected to be a deep neck infection secondary to a
      retropharyngeal abscess. After surgery, the patient was diagnosed with a
      retropharyngeal abscess and concurrent cystic lymphangioma. The lesions improved
      after intraoral incision and drainage, and administration of antibiotics.
      CONCLUSION: Lymphangiomas and retropharyngeal abscesses are both known to be more
      common in children than in adults. However, we found no other reports of
      concomitant presentation of lymphangioma and retropharyngeal abscess in the
      literature.

PMID- 24885484
TI  - A case of herpes zoster uveitis with severe hyphema.
AB  - BACKGROUND: Uveitis sometimes causes hyphema, but severe hyphema as a
      complication following herpes zoster uveitis has rarely been reported. We report
      a rare case of zoster sine herpete with unusually severe hyphema. CASE
      PRESENTATION: A 41-year-old Japanese female developed hyphema filling almost one
      half of the depth of the anterior chamber after a two-week history of unilateral
      anterior uveitis. Hyphema persisted for four weeks while sectorial iris atrophy
      became gradually apparent. Systemic prednisolone and valaciclovir resulted in
      prompt resolution of uveitis and hyphema. Serum anti-varicella zoster virus (VZV)
      IgG measured by enzyme immunoassay was 116 at presentation and decreased to 20.3
      four month later. In addition, the antibody level in aqueous humor was almost 10
      fold higher than that in serum examined 9 months after presentation. Because
      there was no skin lesion, this case was diagnosed as zoster sine herpete. The
      patient underwent cataract operation due to secondary cataract. The final visual
      acuity in decimal notation was 1.0, but complications such as severe iris
      atrophy, wide anterior synechiae, corneal opacity, and decrease in corneal
      endothelial cell count remained. CONCLUSION: Zoster sine herpete is an important
      differential diagnosis in a case of acute anterior uveitis with severe hyphema,
      although such cases are quite rare. Measurement of anti-VZV IgG levels by enzyme
      immunoassay in aqueous humor and serum would be useful in the diagnosis of VZV
      reactivation. Prompt diagnosis and administration of corticosteroids and anti
      herpes virus medication may improve the outcome.

PMID- 24885485
TI  - Abandoning sex: multiple origins of asexuality in the ciliate Tetrahymena.
AB  - BACKGROUND: By segregating somatic and germinal functions into large, compound
      macronuclei and small diploid micronuclei, respectively, ciliates can explore
      sexuality in ways other eukaryotes cannot. Sex, for instance, is not for
      reproduction but for nuclear replacement in the two cells temporarily joined in
      conjugation. With equal contributions from both conjugants, there is no cost of
      sex which theory predicts should favor asexuality. Yet ciliate asexuality is
      rare. The exceptional Tetrahymena has abandoned sex through loss of the
      micronucleus; its amicronucleates are abundant in nature where they reproduce by
      binary fission but never form conjugating pairs. A possible reason for their
      abundance is that the Tetrahymena macronucleus does not accumulate mutations as
      proposed by Muller's ratchet. As such, Tetrahymena amicronucleates have the
      potential to be very old. This study used cytochrome oxidase-1 barcodes to
      determine the phylogenetic origin and relative age of amicronucleates isolated
      from nature. RESULTS: Amicronucleates constituted 25% of Tetrahymena-like wild
      isolates. Of the 244 amicronucleates examined for cox1 barcodes, 237 belonged to
      Tetrahymena, seven to other genera. Sixty percent originated from 12 named
      species or barcoded strains, including the model Tetrahymena thermophila, while
      the remaining 40% represent 19 putative new species, eight of which have
      micronucleate counterparts and 11 of which are known only as amicronucleates. In
      some instances, cox1 haplotypes were shared among micronucleate and
      amicronucleates collected from the same source. Phylogenetic analysis showed that
      most amicronucleates belong to the "borealis" clade in which mating type is
      determined by gene rearrangement. Some amicronucleate species were clustered on
      the SSU phylogenetic tree and had longer branch lengths, indicating more ancient
      origin. CONCLUSIONS: Naturally occurring Tetrahymena amicronucleates have
      multiple origins, arising from numerous species. Likely many more new species
      remain to be discovered. Shared haplotypes indicate that some are of contemporary
      origin, while phylogeny indicates that others may be millions of years old. The
      apparent success of amicronucleate Tetrahymena may be because macronuclear
      assortment and recombination allow them to avoid Muller's ratchet, incorporate
      beneficial mutations, and evolve independently of sex. The inability of
      amicronucleates to mate may be the result of error(s) in mating type gene
      rearrangement.

PMID- 24885487
TI  - Small cell carcinoma of the prostate presenting with skin metastasis: a case
      report.
AB  - INTRODUCTION: Small cell carcinoma of the prostate is a very rare and aggressive
      type of prostatic cancer. Most cases are diagnosed at advanced stage due to early
      metastasis. The bones, liver, regional and distant lymph nodes are the most
      common sites of metastasis of small cell carcinoma of the prostate. Skin
      metastasis of small cell carcinoma of the prostate is a very rare entity due to
      the uncommon metastatic site. Here, we describe the case of a patient with small
      cell carcinoma of the prostate which metastasized to his skin. CASE PRESENTATION:
      A 74-year-old Caucasian man presented to another urology center for mild lower
      urinary tract symptoms in 2003. His prostate-specific antigen was 23 ng/mL.
      According to the physical examination signs and prostate-specific antigen, he
      underwent a transrectal ultrasound-guided prostate biopsy. The pathologic
      examination of his prostate revealed a Gleason score: 3 + 4 = 7 adenocarcinoma of
      the prostate. Investigations showed stage T2N0M0 disease and he was treated with
      radiotherapy to his pelvic lymph nodes and prostate. Six years after the initial
      diagnosis, he complained of a palpable left-side 2 * 2 cm subcutaneous solitary
      mass localized just behind his scapula. The results of his laboratory tests
      including serum acid phosphatase and prostate-specific antigen were in normal
      ranges. Our general surgery department performed a diagnostic biopsy of the mass
      and totally excised the lesion. The pathologic examination of the mass showed
      small cell carcinoma metastasis with chromogranin + and the pathologist advised
      us to examine the lung or prostate for the primary tumor. The patient undertook a
      transrectal ultrasound-guided prostate biopsy and the pathologic result revealed
      small cell carcinoma within residual adenocarcinoma. We investigated the other
      sites for metastasis and restaging investigations showed a 1cm metastatic lesion
      in his liver. Our medical oncology department decided to treat him with
      combination chemotherapy with etoposide and cisplatin in six cycles; however, he
      died due to disseminated myocardial infarction before starting the fifth
      combination chemotherapy cycle. CONCLUSIONS: Clinicians should keep in mind that
      early diagnosis of this disease is very difficult due to early metastatic spread
      of small cell carcinoma and lack of concordant elevation of prostate-specific
      antigen. There is no accepted standard treatment modality for this pathology and
      overall prognosis is poor.

PMID- 24885486
TI  - The ENHANCES study--Enhancing Head and Neck Cancer patients' Experiences of
      Survivorship: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Few cancers pose greater challenges than head and neck (H&N) cancer.
      Residual effects following treatment include body image changes, pain, fatigue
      and difficulties with appetite, swallowing and speech. Depression is a common
      comorbidity. There is limited evidence about ways to assist patients to achieve
      optimal adjustment after completion of treatment. In this study, we aim to
      examine the effectiveness and feasibility of a model of survivorship care to
      improve the quality of life of patients who have completed treatment for H&N
      cancer. METHODS/DESIGN: This is a preliminary study in which 120 patients will be
      recruited. A prospective randomised controlled trial of the H&N Cancer Survivor
      Self-management Care Plan (HNCP) involving pre- and post-intervention assessments
      will be used. Consecutive patients who have completed a defined treatment
      protocol for H&N cancer will be recruited from two large cancer services and
      randomly allocated to one of three study arms: (1) usual care, (2) information in
      the form of a written resource or (3) the HNCP delivered by an oncology nurse who
      has participated in manual-based training and skill development in patient self
      management support. The trained nurses will meet patients in a face-to-face
      interview lasting up to 60 minutes to develop an individualised HNCP, based on
      principles of chronic disease self-management. Participants will be assessed at
      baseline, 3 and 6 months. The primary outcome measure is quality of life. The
      secondary outcome measures include mood, self-efficacy and health-care
      utilisation. The feasibility of implementing this intervention in routine
      clinical care will be assessed through semistructured interviews with
      participating nurses, managers and administrators. Interviews with patients who
      received the HNCP will explore their perceptions of the HNCP, including factors
      that assisted them in achieving behavioural change. DISCUSSION: In this study, we
      aim to improve the quality of life of a patient population with unique needs by
      means of a tailored self-management care plan developed upon completion of
      treatment. Delivery of the intervention by trained oncology nurses is likely to
      be acceptable to patients and, if successful, will be a model of care that can be
      implemented for diverse patient populations. TRIAL REGISTRATION:
      ACTRN12613000542796 (registered on 15 May 2013).

PMID- 24885488
TI  - Bilateral chylothorax following neck dissection: a case report.
AB  - BACKGROUND: Chylothorax is an extremely rare but potentially life-threatening
      complication after radical neck dissection. We report the case of a bilateral
      chylothorax after total thyroidectomy and cervico-central and cervico-lateral
      lymphadenectomy for thyroid carcinoma. CASE PRESENTATION: A 40-year-old European
      woman underwent total thyroidectomy and neck dissection for papillary thyroid
      carcinoma. Postoperatively she developed dyspnoea and pleural effusion. A
      chylothorax was found and the initial conservative therapy was not successful.
      She had to be operated on again and the thoracic duct was legated. CONCLUSION:
      The case presentation reports a very rare complication after total thyroidectomy
      and neck dissection, but it has to be kept in mind to prevent dangerous
      complications.

PMID- 24885489
TI  - The use of global positional satellite location in dementia: a feasibility study
      for a randomised controlled trial.
AB  - BACKGROUND: Getting lost outside is stressful for people with dementia and their
      caregivers and a leading cause of long-term institutionalisation. Although Global
      Positional Satellite (GPS) location has been promoted to facilitate safe walking,
      reduce caregivers' anxiety and enable people with dementia to remain at home,
      there is little high quality evidence about its acceptability, effectiveness or
      cost-effectiveness. This observational study explored the feasibility of
      recruiting and retaining participants, and the acceptability of outcome measures,
      to inform decisions about the feasibility of a randomised controlled trial (RCT).
      METHODS: People with dementia who had been provided with GPS devices by local
      social-care services and their caregivers were invited to participate in this
      study. We undertook interviews with people with dementia, caregivers and
      professionals to explore the perceived utility and challenges of GPS location,
      and assessed quality of life (QoL) and mental health. We piloted three methods of
      calculating resource use: caregiver diary; bi-monthly telephone questionnaires;
      and interrogation of health and social care records. We asked caregivers to
      estimate the time spent searching if participants became lost before and whilst
      using GPS. RESULTS: Twenty people were offered GPS locations services by social
      care services during the 8-month recruitment period. Of these, 14 agreed to be
      referred to the research team, 12 of these participated and provided data. Eight
      people with dementia and 12 caregivers were interviewed. Most participants and
      professionals were very positive about using GPS. Only one person completed a
      diary. Resource use, anxiety and depression and QoL questionnaires were
      considered difficult and were therefore declined by some on follow-up. Social
      care records were time consuming to search and contained many omissions.
      Caregivers estimated that GPS reduced searching time although the accuracy of
      this was not objectively verified. CONCLUSIONS: Our data suggest that a RCT will
      face challenges not least that widespread enthusiasm for GPS among social-care
      staff may challenge recruitment and its ready availability may risk contamination
      of controls. Potential primary outcomes of a RCT should not rely on caregivers'
      recall or questionnaire completion. Time spent searching (if this could be
      accurately captured) and days until long-term admission are potentially suitable
      outcomes.

PMID- 24885490
TI  - Non-celiac gluten sensitivity - why worry?
AB  - Wheat, once thought to be a critical ingredient in a healthy diet, has become a
      major threat, according to public opinion. The term non-celiac gluten sensitivity
      has been widely adopted to describe a clinical entity characterized by symptoms
      induced by gluten without the diagnostic criteria found in other gluten-related
      disorders. However, it has not been shown that gluten per se is involved, and it
      can be debated if the condition is a disease. Nevertheless, a large number of
      individuals go gluten-free, avoiding wheat, rye and barley, even without a
      defined medical cause. In a study in BMC Medicine, Volta and colleagues from
      Italy report on a large, multicenter attempt to enumerate the prevalence of non
      celiac gluten sensitivity in secondary gastroenterology care. They found that
      approximately 3% of their more than 12,000 patients fulfilled their criteria for
      non-celiac gluten sensitivity. However, we are still challenged with finding
      stricter clinical criteria for the condition, developing a usable clinical
      approach for gluten challenge in these individuals, and understanding the
      pathogenesis of the condition.

PMID- 24885491
TI  - The patient perspective on overactive bladder: a mixed-methods needs assessment.
AB  - BACKGROUND: While overactive bladder is often managed in the primary care
      setting, a number of barriers including embarrassment, poor communication, and
      low patient adherence contribute to the under-treatment of patients with
      burdensome urinary symptoms. In order to address these challenges, it is crucial
      to have a fundamental understanding of patient perspectives toward OAB and
      urinary symptoms. To meet this aim, researchers designed and conducted a study to
      identify patients' knowledge, experiences and attitudes, barriers to treatment
      adherence, and desires and tendencies regarding patient/clinician communications.
      METHODS: A mixed-methods qualitative/quantitative needs assessment of patients
      with overactive bladder and/or urinary symptoms. Researchers conducted in-depth
      qualitative interviews via telephone with 40 patients. Interview results informed
      the design and dissemination of a quantitative survey, which was completed by 200
      self-selected respondents who had previously identified themselves as having
      overactive bladder or bladder problems. Statistical and qualitative analysis of
      results were conducted. RESULTS: Among survey respondents, an average of 3.5
      years elapsed between symptom onset and seeking diagnosis by a physician. In the
      long term most patients do not experience improvement in symptoms. Medication non
      adherence is common and is related to therapy effectiveness and adverse effects.
      Patients clearly indicate that communication and patient/physician relationships
      are important to them and they would prefer the clinician initiate the
      conversation on overactive bladder. Patient experiences, perspectives, and
      attitudes toward their bladder symptoms differ in many ways from clinicians'
      assumptions. CONCLUSIONS: The significant time gap between symptom onset and
      diagnosis indicates ongoing need for screening and diagnosis of overactive
      bladder. Contrary to guideline recommendations, urinalysis and physical
      examination are not widely used in clinical practice. Many patients experience no
      improvement in symptoms over time. Patients indicate that clinician/patient
      relationships and communication regarding their condition are important.

PMID- 24885492
TI  - Health inequalities and development plans in Iran; an analysis of the past three
      decades (1984-2010).
AB  - INTRODUCTION: Reducing inequalities in health care is one of the main challenges
      in all countries. In Iran as in other oil-exporting upper middle income
      countries, we expected to witness fewer inequalities especially in the health
      sector with the increase in governmental revenues. METHODS: This study presents
      an inequalities assessment of health care expenditures in Iran. We used data from
      the Household Income and Expenditure Survey (HIES) in Iran from 1984-2010. The
      analysis included 308,735 urban and 342,532 rural households. RESULTS: The
      results suggest heightened inequality in health care expenditures in Iran over
      the past three decades, including an increase in the gap between urban and rural
      areas. Furthermore, inflation has affected the poor more than the rich. The
      Kakwani progressivity index in all years is positive, averaging 0.436 in rural
      and 0.470 in urban areas during the time period of analysis. Compared to
      inequality in income distribution over the last 30 years, health expenditures
      continuously show more inequality and progressivity over the same period of time.
      CONCLUSIONS: According to the result of our study, during this period Iran
      introduced four National Development Plans (NDPs); however, the NDPs failed to
      provide sustainable strategies for reducing inequalities in health care
      expenditures. Policies that protect vulnerable groups should be prioritized.

PMID- 24885493
TI  - Polycomb group protein expression during differentiation of human embryonic stem
      cells into pancreatic lineage in vitro.
AB  - BACKGROUND: Polycomb Group (PcG) proteins are chromatin modifiers involved in
      early embryonic development as well as in proliferation of adult stem cells and
      cancer cells. PcG proteins form large repressive complexes termed Polycomb
      Repressive Complexes (PRCs) of which PRC1 and PRC2 are well studied.
      Differentiation of human Embryonic Stem (hES) cells into insulin producing cells
      has been achieved to limited extent, but several aspects of differentiation
      remain unexplored. The PcG protein dynamics in human embryonic stem (hES) cells
      during differentiation into pancreatic lineage has not yet been reported. In the
      present study, the expression of RING1A, RING1B, BMI1, CBX2, SUZ12, EZH2, EED and
      JARID2 during differentiation of hES cells towards pancreatic lineage was
      examined. RESULTS: In-house derived hES cell line KIND1 was used to study
      expression of PcG protein upon spontaneous and directed differentiation towards
      pancreatic lineage. qRT-PCR analysis showed expression of gene transcripts for
      various lineages in spontaneously differentiated KIND1 cells, but no
      differentiation into pancreatic lineage was observed. Directed differentiation
      induced KIND1 cells grown under feeder-free conditions to transition from
      definitive endoderm (Day 4), primitive gut tube stage (Day 8) and pancreatic
      progenitors (Day 12-Day 16) as evident from expression of SOX17, PDX1 and SOX9 by
      qRT-PCR and Western blotting. In spontaneously differentiating KIND1 cells,
      RING1A and SUZ12 were upregulated at day 15, while other PcG transcripts were
      downregulated. qRT-PCR analysis showed transcripts of RING1B, BMI1, SUZ12, EZH2
      and EED were upregulated, while RING1A and CBX2 expression remained low and
      JARID2 was downregulated during directed differentiation of KIND1 cells.
      Upregulation of BMI1, EZH2 and SUZ12 during differentiation into pancreatic
      lineage was also confirmed by Western blotting. Histone modifications such as
      H3K27 trimethylation and monoubiquitinylation of H2AK119 increased during
      differentiation into pancreatic lineage as seen by Western blotting. CONCLUSION:
      Our study shows expression of PcG proteins was distinct during spontaneous and
      directed differentiation. Differentiation into pancreatic lineage was achieved by
      directed differentiation approach and was associated with increased expression of
      PcG proteins RING1B, BMI1, EZH2 and SUZ12 accompanied by increase in
      monoubiquitinylation of H2AK119 and trimethylation of H3K27.

PMID- 24885495
TI  - Attitudes of physicians and patients towards disclosure of genetic information to
      spouse and first-degree relatives: a case study from Turkey.
AB  - BACKGROUND: When considering the principle of medical confidentiality, disclosure
      of genetic information constitutes a special case because of the impact that this
      information can have on the health and the lives of relatives. The aim of this
      study is to explore the attitudes of Turkish physicians and patients about
      sharing information obtained from genetic tests. METHODS: The study was carried
      out in Kocaeli, Turkey. Participants were either paediatricians and
      gynaecologists registered in Kocaeli, or patients coming to the genetic diagnosis
      centre for karyotype analysis in 2008. A self-administered paper questionnaire
      was given to the physicians, and face-to-face structured interviews were
      conducted with patients. We used a case study involving a man who was found to be
      a balanced chromosome carrier as a result of a test conducted after his first
      baby was born with Down's syndrome. However, he refused to share this information
      with his wife or his siblings. Percentages of characteristics and preferences of
      the participants were calculated, and the results were analysed using Kruskal
      Wallis test. RESULTS: A total of 155 physicians (68% response rate) and 104
      patients (46% response rate) were participated in the study. Twenty-six percent
      of physicians and 49% of patients believed that genetic information belongs to
      the whole family. When participants were asked with whom genetic information
      should be shared for the case study, most of the physicians and patients thought
      the physician should inform the spouse (79%, 85%, respectively). They were less
      likely to support a physician informing a sibling (41%, 53%, respectively);
      whereas, many thought the testee has an obligation to inform siblings (70%, 94%,
      respectively). CONCLUSIONS: Although Turkey's national regulations certainly
      protect the right of privacy of the testee, the participants in our study appear
      to believe that informing the spouse, who is not personally at risk of serious
      damage, is the physician's responsibility, while informing siblings, is the
      testee's responsibility. Therefore we believe that opening ethical discussions
      with clinicians about the sharing of genetic information, establishing guidelines
      for practice and sharing these guidelines and the reasons behind them with the
      wider population, will help to pre-empt ethical dilemmas.

PMID- 24885494
TI  - Dynamics of soluble and cellular inflammatory markers in nasal lavage obtained
      from cystic fibrosis patients during intravenous antibiotic treatment.
AB  - BACKGROUND: In cystic fibrosis (CF) patients, the upper airways display the same
      ion channel defect as evident in the lungs, resulting in chronic inflammation and
      infection. Recognition of the sinonasal area as a site of first and persistent
      infection with pathogens, such as Pseudomonas aeruginosa, reinforces the "one
      airway" hypothesis. Therefore, we assessed the effect of systemic antibiotics
      against pulmonary pathogens on sinonasal inflammation. METHODS: Nasal lavage
      fluid (NLF) from 17 CF patients was longitudinally collected prior to and during
      elective intravenous (i.v.) antibiotic treatment to reduce pathogen burden and
      resulting inflammation (median treatment time at time of analysis: 6 days).
      Samples were assessed microbiologically and cytologically. Cytokine and chemokine
      expression was measured by Cytometric Bead Array and ELISA (interleukin (IL)
      1beta, IL-6, IL-8, MPO, MMP9, RANTES and NE). Findings were compared with
      inflammatory markers from NLF obtained from 52 healthy controls. RESULTS:
      Initially, the total cell count of the NLF was significantly higher in CF
      patients than in controls. However after i.v. antibiotic treatment it decreased
      to a normal level. Compared with controls, detection frequencies and absolute
      concentrations of MPO, IL-8, IL-6 and IL-1beta were also significantly higher in
      CF patients. The detection frequency of TNF was also higher. Furthermore, during
      i.v. therapy sinonasal concentrations of IL-6 decreased significantly (P =
      0.0059), while RANTES and MMP9 levels decreased 10-fold and two-fold,
      respectively. PMN-Elastase, assessed for the first time in NFL, did not change
      during therapy. CONCLUSIONS: Analysis of NLF inflammatory markers revealed
      considerable differences between controls and CF patients, with significant
      changes during systemic i.v. AB treatment within just 6 days. Thus, our data
      support further investigation into the collection of samples from the epithelial
      surface of the upper airways by nasal lavage as a potential diagnostic and
      research tool.

PMID- 24885496
TI  - Investigating perturbed pathway modules from gene expression data via structural
      equation models.
AB  - BACKGROUND: It is currently accepted that the perturbation of complex
      intracellular networks, rather than the dysregulation of a single gene, is the
      basis for phenotypical diversity. High-throughput gene expression data allow to
      investigate changes in gene expression profiles among different conditions.
      Recently, many efforts have been made to individuate which biological pathways
      are perturbed, given a list of differentially expressed genes (DEGs). In order to
      understand these mechanisms, it is necessary to unveil the variation of genes in
      relation to each other, considering the different phenotypes. In this paper, we
      illustrate a pipeline, based on Structural Equation Modeling (SEM) that allowed
      to investigate pathway modules, considering not only deregulated genes but also
      the connections between the perturbed ones. RESULTS: The procedure was tested on
      microarray experiments relative to two neurological diseases: frontotemporal
      lobar degeneration with ubiquitinated inclusions (FTLD-U) and multiple sclerosis
      (MS). Starting from DEGs and dysregulated biological pathways, a model for each
      pathway was generated using databases information biological databases, in order
      to design how DEGs were connected in a causal structure. Successively, SEM
      analysis proved if pathways differ globally, between groups, and for specific
      path relationships. The results confirmed the importance of certain genes in the
      analyzed diseases, and unveiled which connections are modified among them.
      CONCLUSIONS: We propose a framework to perform differential gene expression
      analysis on microarray data based on SEM, which is able to: 1) find relevant
      genes and perturbed biological pathways, investigating putative sub-pathway
      models based on the concept of disease module; 2) test and improve the generated
      models; 3) detect a differential expression level of one gene, and differential
      connection between two genes. This could shed light, not only on the mechanisms
      affecting variations in gene expression, but also on the causes of gene-gene
      relationship modifications in diseased phenotypes.

PMID- 24885498
TI  - Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed
      uninfected infants: protective mechanism or immunodeficiency.
AB  - BACKGROUND: Reports of increased morbidity and mortality from infectious diseases
      among HIV Exposed Uninfected (HEU) infants have raised concern about a possible
      underlying immunodeficiency among them. The objective of this study was to assess
      the immunological profile of HEU infants born to mothers exhibiting different
      levels of HIV-1 viremia at the time of delivery. METHODS: Study subjects were
      enrolled in the Centre maternel et infantile sur le SIDA (CMIS) mother-child
      cohort between 1997 and 2010 (n =585). Infant CD4+ T cell, CD8+ T cell and CD19+
      B cell counts were assessed at 2 and 6 months of age, and compared among HEU
      infants in groups defined by maternal viral load (VL) at the time of delivery (VL
      < 50 copies/ml, VL 50-1000 copies/ml, and VL > 1000 copies/ml) in a multivariable
      analysis. RESULTS: At 2 months of age, infants born to mothers with VL > 1000
      copies/ml had lower CD4+ T cell counts compared to those born to mothers with VL
      < 50 copies/ml at the time of delivery (44.3% versus 48.3%, p = 0.007, and 2884
      vs. 2432 cells/mm3, p = 0.02). These differences remained significant after
      adjusting for maternal and infant antiretroviral drug use, gender, race and
      gestational age, and persisted at 6 months of age. There were no differences in
      CD8+ T cell count or absolute CD19+ B cell count between groups, though higher
      CD19+ B cell percentage was seen among infants born to mothers with VL > 1000
      copies/ml. CONCLUSIONS: These results suggest that exposure to high levels of HIV
      1 viremia in utero, even in the absence of perinatal transmission, may affect the
      infant's developing immune system. While further work needs to be done to confirm
      these findings, they reinforce the need for optimal treatment of HIV infected
      pregnant women, and careful follow-up of HEU infants.

PMID- 24885497
TI  - Levels of physical activity among a nationally representative sample of people in
      early old age: results of objective and self-reported assessments.
AB  - BACKGROUND: Detailed assessment of physical activity (PA) in older adults is
      required to comprehensively describe habitual PA-levels in this growing
      population segment. Current evidence of population PA-levels is predominantly
      based on self-report. METHODS: We examined PA and sedentary behaviour in a
      nationally representative sample of British people aged 60-64, using individually
      calibrated combined heart-rate and movement sensing and a validated questionnaire
      (EPAQ2), and the socio-demographic and behavioural factors that may explain
      between-individual variation in PA. RESULTS: Between 2006-2010, 2224 participants
      completed EPAQ2 capturing the past year's activity in four domains (leisure,
      work, transportation and domestic life) and 1787 participants provided 2-5 days
      of combined-sensing data. According to objective estimates, median(IQR) physical
      activity energy expenditure (PAEE) was 33.5 (25.3-42.2) and 35.5 (26.6- 47.3)
      kJ/kg/day for women and men, respectively. Median (IQR) time spent in moderate-to
      vigorous PA (MVPA; >3MET), light-intensity PA (1.5-3 MET) and sedentary (<1.5
      MET) was 26.0 (12.3-48.1) min/day, 5.4 (4.2-6.7) h/day and 18.0 (16.6-19.4)
      h/day, respectively, in women; and 41.0 (18.8-73.0) min/day, 5.2 (4.0-6.5) h/day
      and 17.9 (16.3-19.4) h/day in men. PAEE and time spent in MVPA were lower and
      sedentary time was greater in obese individuals, those with poor health, and
      those with lower educational attainment (women only). Questionnaire-derived PAEE
      and MVPA tended to have similar patterns of variation across socio-demographic
      strata. In the whole sample, domestic PA had the greatest relative contribution
      to total questionnaire-derived PAEE (58%), whereas occupational PA was the main
      driver among employed participants (54%). Only 2.2% of participants achieved an
      average of >30 min MVPA per day combined with >60 min strength-training per week.
      CONCLUSIONS: The use of both self-report and objective monitoring to assess PA in
      early old age provides important information on the domains of PA, PAEE and time
      spent at different intensity levels. Our findings suggest PA levels are generally
      low and observed patterns of variation indicate specific subgroups who might
      benefit from targeted interventions to increase PA.

PMID- 24885499
TI  - Insecticidal and repellent activities of pyrethroids to the three major
      pyrethroid-resistant malaria vectors in western Kenya.
AB  - BACKGROUND: The dramatic success of insecticide treated nets (ITNs) and long
      lasting insecticidal nets (LLINs) in African countries has been countered by the
      rapid development of pyrethroid resistance in vector mosquitoes over the past
      decade. One advantage of the use of pyrethroids in ITNs is their excito
      repellency. Use of the excito-repellency of pyrethroids might be biorational,
      since such repellency will not induce or delay the development of any
      physiological resistance. However, little is known about the relationship between
      the mode of insecticide resistance and excito-repellency in pyrethroid-resistant
      mosquitoes. METHODS: Differences in the reactions of 3 major malaria vectors in
      western Kenya to pyrethroids were compared in laboratory tests. Adult
      susceptibility tests were performed using World Health Organization (WHO) test
      tube kits for F1 progenies of field-collected An. gambiae s.s., An. arabiensis,
      and An. funestus s.s., and laboratory colonies of An. gambiae s.s. and An.
      arabiensis. The contact repellency to pyrethroids or permethrin-impregnated LLINs
      (Olyset(r) Nets) was evaluated with a simple choice test modified by WHO test
      tubes and with the test modified by the WHO cone bioassay test. RESULTS: Field
      collected An. gambiae s.s., An. arabiensis, and An. funestus s.s. showed high
      resistance to both permethrin and deltamethrin. The allelic frequency of the
      point mutation in the voltage-gated sodium channel (L1014S) in An. gambiae s.s.
      was 99.3-100%, while no point mutations were detected in the other 2 species. The
      frequency of takeoffs from the pyrethroid-treated surface and the flying times
      without contacting the surface increased significantly in pyrethroid-susceptible
      An. gambiae s.s. and An. arabiensis colonies and wild An. arabiensis and An.
      funestus s.s. colonies, while there was no significant increase in the frequency
      of takeoffs or flying time in the An. gambiae s.s. wild colony. CONCLUSION: A
      different repellent reaction was observed in the field-collected An. gambiae s.s.
      than in An. arabiensis and An. funestus s.s. It might be that resistant
      mosquitoes governed by knockdown resistance (kdr) loose repellency to
      pyrethroids, whereas those lacking kdr maintain high repellency irrespective of
      their possessing metabolic resistance factors to pyrethroids. Further genetic
      evaluation is required for the demonstration of the above hypothesis.

PMID- 24885500
TI  - Adult primary paratesticular mesenchymal tumors with emphasis on a case
      presentation and discussion of spermatic cord leiomyosarcoma.
AB  - BACKGROUND: The aim of this report is related to adult primary paratesticular
      mesenchymal tumors with emphasis on a case presentation and discussion of the
      spermatic cord leiomyosarcoma. Primary paratesticular tumors are rare, only
      accounting for 7% to 10% of all intrascrotal tumors. In adults, more than 75% of
      these lesions arise from the spermatic cord, 20% being leiomyosarcoma. Tumor
      grade, stage, histologic type, and lymph node involvement are independently
      predictive of prognosis. FINDINGS: The case report concerns a 81-year-old man
      presented with a 3-year history of painless lump in the right hemiscrotum.
      Scrotal examination demonstrated a 5.1-cm, firm-to-hard mass attached to the
      spermatic cord. Scrotal ultrasound scan revealed a heterogeneous mass separate
      from the testis. He was treated with an radical orchi-funicolectomy.
      Histologically the lesion is composed of spindled cells with often elongated,
      blunt-ended nuclei and variably eosinophilic cytoplasm. Areas with pleomorphic
      morphology are present. The level of mitotic activity is equal to 3/10 HPF in the
      areas with spindle cell morphology and to 12/10 HPF in the areas with pleomorphic
      morphology. The final diagnosis was that a leiomyosarcoma of the spermatic cord,
      with grade 1 and grade 2 areas, stage pT2b cN0 and cM0. The patient has been
      followed up for 3 months with CT scans and shows no signs of recurrence.
      CONCLUSIONS: Spermatic cord leiomyosarcoma, although rare, should be one of the
      first differential diagnoses for a firm-to-hard lump in the cord. Apart from
      radical orchi-funicolectomy, there has been added benefit of adjuvant
      radiotherapy to prevent any loco-regional lymph node recurrence. VIRTUAL SLIDES:
      The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1613030331125632.

PMID- 24885502
TI  - Primary papillary carcinoma of the thymus with invasion into subcutaneous tissue
      through the sternum.
AB  - Thymic carcinoma is a rare malignant neoplasm. We present a Japanese case of
      papillary carcinoma of thymus in a 64-year-old man that invaded into subcutaneous
      tissue penetrating the sternum. We describe the clinical and pathologic features
      of this extremely rare thymic epithelial tumor, with disease-free survival at
      three years of follow-up. 

PMID- 24885503
TI  - Objectively determined habitual physical activity in South African adolescents:
      the PAHL study.
AB  - BACKGROUND: There is limited data on objectively determined habitual physical
      activity (PA) in 16-year old South African adolescents. The purpose of this study
      was to objectively determine the habitual PA of adolescents from the North West
      Province of South Africa by race and gender. METHODS: Adolescents (137 girls, 89
      boys) from the ongoing Physical Activity and Health Longitudinal Study (PAHL
      study), participated in the present study. Habitual PA was objectively recorded
      by means of the Actiheart(r) over a period of 7 days. Time spent in moderate-to
      vigorous intensity physical activity (MVPA) was assessed. RESULTS: Average MVPA
      for the study sample was 50.9 +/- 40.3 minutes/day. Girls were significantly more
      active than boys expending more time in MVPA (61.13 +/- 52.2 minutes/day; p <
      0.05) than boys (35.0 +/- 32.9 minutes/day). Although white adolescents spent
      more time in MVPA than black adolescents, there was no significant difference in
      MVPA between black (47.87 +/- 39.6 minutes/day; p = 0.58) and white adolescents
      (59.5 +/- 41.8 minutes/day). CONCLUSION: Physical activity varies by both gender
      and race in adolescents from the North West Province of South Africa. Objectively
      determined data from our study indicates that girls habitually spend more time in
      MVPA per day than boys, and that white adolescents habitually engage in more MVPA
      than black adolescents. Seeing as the average MVPA per day for the entire study
      sample falls below the recommended daily average of 60 minutes/day, adolescents
      should be the foremost targets of interventions aimed at enhancing habitual PA.

PMID- 24885501
TI  - Longissimus dorsi transcriptome analysis of purebred and crossbred Iberian pigs
      differing in muscle characteristics.
AB  - BACKGROUND: The two main genetic types in Iberian pig production show important
      phenotypic differences in growth, fattening and tissue composition since early
      developmental stages. The objective of this work was the evaluation of muscle
      transcriptome profile in piglets of both genetic types, in order to identify
      genes, pathways and regulatory factors responsible for their phenotypic
      differences. Contemporary families coming from pure Iberian pigs (IB) or from
      crossing with Duroc boars (DU*IB) were generated. Piglets (14 from each genetic
      type) were slaughtered at weaning (28 days) and longissimus dorsi was sampled for
      composition and gene expression studies. RNA was obtained and hybridized to
      Affymetrix Porcine Genechip expression arrays. RESULTS: Loin muscle chemical
      composition showed significant differences between genetic types in intramuscular
      fat content (6.1% vs. 4.3% in IB and DUxIB animals, respectively, P = 0.009) and
      in saturated (P = 0.019) and monounsaturated fatty acid proportions (P = 0.044).
      The statistical analysis of gene expression data allowed the identification of
      256 differentially expressed (DE) genes between genetic types (FDR < 0.10), 102
      upregulated in IB and 154 upregulated in DU*IB. Transcript differences were
      validated for a subset of DE genes by qPCR. We observed alteration in biological
      functions related to extracellular matrix function and organization, cellular
      adhesion, muscle growth, lipid metabolism and proteolysis. Candidate genes with
      known effects on muscle growth were found among the DE genes upregulated in
      DU*IB. Genes related to lipid metabolism and proteolysis were found among those
      upregulated in IB. Regulatory factors (RF) potentially involved in the expression
      differences were identified by calculating the regulatory impact factors. Twenty
      nine RF were found, some of them with known relationship with tissue development
      (MSTN, SIX4, IRX3), adipogenesis (CEBPD, PPARGC1B), or extracellular matrix
      processes (MAX, MXI1). Correlation among the expression of these RF and DE genes
      show relevant differences between genetic types. CONCLUSION: These results
      provide valuable information about genetic mechanisms determining the phenotypic
      differences on growth and meat quality between the genetic types studied, mainly
      related to the development and function of the extracellular matrix and also to
      some metabolic processes as proteolysis and lipid metabolism. Transcription
      factors and regulatory mechanisms are proposed for these altered biological
      functions.

PMID- 24885504
TI  - Simplified method to perform CLARITY imaging.
AB  - BACKGROUND: Imaging methods are used widely to understand structure of brain and
      other biological objects. However, sample penetration by light microscopy is
      limited due to light scattering by the tissue. A number of methods have been
      recently developed to solve this problem. In one approach (SeeDB) simple
      procedure for clarifying brain samples for imaging was described. However, this
      method is not compatible with immunostaining approach as SeeDB-prepared tissue is
      not permeable to the antibodies. Another technique for clearing brain tissue
      (CLARITY) was optimized for immunochemistry, but this method technically much
      more demanding than SeeDB. RESULTS: Here we report optimized protocol for imaging
      of brain samples (CLARITY2). We have simplified and shortened the original
      protocol. Following hydrogel fixation, we cut brain tissue to 1-1.5 mm thick
      coronal slices. This additional step enabled us to accelerate and simplify
      clearing, staining and imaging steps when compared to the original protocol. We
      validated the modified protocol in imaging experiments with brains from line M
      Thy1-GFP mouse and in immunostaining experiments with antibodies against
      postsynaptic protein PSD-95 and striatal-specific protein DARPP32. CONCLUSIONS:
      The original CLARITY protocol was optimized and simplified. Application of the
      modified CLARITY2 protocol could be useful for a broad range of scientists
      working in neurobiology and developmental biology.

PMID- 24885505
TI  - More than fishing in the dark: PCR of a dispersed sequence produces simple but
      ultrasensitive Wolbachia detection.
AB  - BACKGROUND: Detecting intracellular bacterial symbionts can be challenging when
      they persist at very low densities. Wolbachia, a widespread bacterial
      endosymbiont of invertebrates, is particularly challenging. Although it persists
      at high titers in many species, in others its densities are far below the
      detection limit of classic end-point Polymerase Chain Reaction (PCR). These low
      titer infections can be reliably detected by combining PCR with DNA
      hybridization, but less elaborate strategies based on end-point PCR alone have
      proven less sensitive or less general. RESULTS: We introduce a multicopy PCR
      target that allows fast and reliable detection of A-supergroup Wolbachia--even at
      low infection titers--with standard end-point PCR. The target is a multicopy
      motif (designated ARM: A-supergroup repeat motif) discovered in the genome of
      wMel (the Wolbachia in Drosophila melanogaster). ARM is found in at least seven
      other Wolbachia A-supergroup strains infecting various Drosophila, the wasp
      Muscidifurax and the tsetse fly Glossina. We demonstrate that end-point PCR
      targeting ARM can reliably detect both high- and low-titer Wolbachia infections
      in Drosophila, Glossina and interspecific hybrids. CONCLUSIONS: Simple end-point
      PCR of ARM facilitates detection of low-titer Wolbachia A-supergroup infections.
      Detecting these infections previously required more elaborate procedures. Our ARM
      target seems to be a general feature of Wolbachia A-supergroup genomes, unlike
      other multicopy markers such as insertion sequences (IS).

PMID- 24885507
TI  - Social relationships and health related behaviors among older US adults.
AB  - BACKGROUND: Health behaviors are a key determinant of health and well-being that
      are influenced by the nature of the social environment. This study examined
      associations between social relationships and health-related behaviors among a
      nationally representative sample of older people. METHODS: We analyzed data from
      three waves (1999-2004) of the US National Health and Nutrition Examination
      Survey (NHANES). Participants were 4,014 older Americans aged 60 and over. Log
      binomial regression models estimated prevalence ratios (PR) for the associations
      between social relationships and each of the following health behaviors: alcohol
      use, smoking, physical activity and dental attendance. RESULTS: Health
      compromising behaviors (smoking, heavy drinking and less frequent dental visits)
      were related to marital status, while physical activity, a health-promoting
      behavior, was associated with the size of friendship networks. Smoking was more
      common among divorced/separated (PR = 2.1; 95% CI: 1.6, 2.7) and widowed (PR =
      1.7; 95% CI: 1.3, 2.3) respondents than among those married or cohabiting, after
      adjusting for socio-demographic background. Heavy drinking was 2.6 times more
      common among divorced/separated and 1.7 times more common among widowed men
      compared to married/cohabiting men, while there was no such association among
      women. For women, heavy drinking was associated with being single (PR = 1.7; 95%
      CI: 1.0, 2.9). Being widowed was related to a lower prevalence of having visited
      a dentist compared to being married or living with a partner (PR = 0.92; 95% CI
      0.86, 0.99). Those with a larger circle of friends were more likely to be
      physically active (PR = 1.17; 95% CI:1.06, 1.28 for 5-8 versus less than 5
      friends). CONCLUSIONS: Social relationships of older Americans were independently
      associated with different health-related behaviors, even after adjusting for
      demographic and socioeconomic determinants. Availability of emotional support did
      not however mediate these associations. More research is needed to assess if
      strengthening social relationships would have a significant impact on older
      people's health behaviors and ultimately improve their health.

PMID- 24885506
TI  - Unmet mental health care need 10-11 years after the 9/11 terrorist attacks: 2011
      2012 results from the World Trade Center Health Registry.
AB  - BACKGROUND: There is little current information about the unmet mental health
      care need (UMHCN) and reasons for it among those exposed to the World Trade
      Center (WTC) terrorist attacks. The purpose of this study was to assess the level
      of UMHCN among symptomatic individuals enrolled in the WTC Health Registry
      (WTCHR) in 2011-2012, and to analyze the relationship between UMHCN due to
      attitudinal, cost, and access factors and mental health symptom severity, mental
      health care utilization, health insurance availability, and social support.
      METHODS: The WTCHR is a prospective cohort study of individuals with reported
      exposure to the 2001 WTC attacks. This study used data from 9,803 adults who
      completed the 2003-2004 (Wave 1) and 2011-2012 (Wave 3) surveys and had
      posttraumatic stress disorder (PTSD) or depression in 2011-2012. We estimated
      logistic regression models relating perceived attitudinal, cost and access
      barriers to symptom severity, health care utilization, a lack of health
      insurance, and social support after adjusting for sociodemographic
      characteristics. RESULTS: Slightly more than one-third (34.2%) of study
      participants reported an UMHCN. Symptom severity was a strong predictor of UMHCN
      due to attitudinal and perceived cost and access reasons. Attitudinal UMHCN was
      common among those not using mental health services, particularly those with
      relatively severe mental health symptoms. Cost-related UMHCN was significantly
      associated with a lack of health insurance but not service usage. Access-related
      barriers were significantly more common among those who did not use any mental
      health services. A higher level of social support served as an important buffer
      against cost and access UMHCN. CONCLUSIONS: A significant proportion of
      individuals exposed to the WTC attacks with depression or PTSD 10 years later
      reported an UMHCN, and individuals with more severe and disabling conditions,
      those who lacked health insurance, and those with low levels of social support
      were particularly vulnerable.

PMID- 24885508
TI  - Seasonal genetic partitioning in the neotropical malaria vector, Anopheles
      darlingi.
AB  - BACKGROUND: Anopheles darlingi is the main malaria mosquito vector in the
      Amazonia region. In spite of being considered a riverine, forest-dwelling
      species, this mosquito is becoming more abundant in peri-urban areas, increasing
      malaria risk. This has been associated with human-driven environmental changes
      such as deforestation. METHODS: Microsatellites were used to characterize A.
      darlingi from seven localities along the Madeira River, Rondonia (Brazil),
      collected in the early and late periods of the rainy season. RESULTS: Two
      genetically distinct subpopulations were detected: one (subpopulation A) was
      associated with the late rainfall period and seems to be ecologically closer to
      the typical forest A. darlingi; the other (subpopulation B) was associated with
      the early rainfall period and is probably more adapted to drier conditions by
      exploiting permanent anthropogenic breeding sites. Results suggest also a pattern
      of asymmetric introgression, with more subpopulation A alleles introgressed into
      subpopulation B. Both subpopulations (and admixed mosquitoes) presented similar
      malaria infection rates, highlighting the potential for perennial malaria
      transmission in the region. CONCLUSIONS: The co-occurrence of two genetically
      distinct subpopulations of A. darlingi adapted to different periods of rainfall
      may promote a more perennial transmission of malaria throughout the year. These
      findings, in a context of strong environmental impact due to deforestation and
      dam construction, have serious implications for malaria epidemiology and control
      in the Amazonian region.

PMID- 24885509
TI  - Wolbachia detection in insects through LAMP: loop mediated isothermal
      amplification.
AB  - BACKGROUND: The bacterium Wolbachia is a promising agent for the biological
      control of vector-borne diseases as some strains have the ability to block the
      transmission of key human disease-causing pathogens. Fast, accurate and
      inexpensive methods of differentiating between infected and uninfected insects
      will be of critical importance as field-based trials of Wolbachia-based bio
      control become increasingly common. FINDINGS: We have developed a specific and
      sensitive method of detecting Wolbachia based on the isothermal DNA
      amplification. This technique can be performed in an ordinary heat block without
      the need for gel-based visualisation, and is effective for a wide variety of
      insect hosts. CONCLUSION: Here we present the development of a rapid, highly
      sensitive and inexpensive method to detect Wolbachia in a variety of insect
      hosts, including key mosquito disease vectors.

PMID- 24885510
TI  - Diagnostic sensitivity of carbohydrate deficient transferrin in heavy drinkers.
AB  - BACKGROUND AND AIM: Carbohydrate deficient transferrin (CDT) is the most specific
      serum biomarker of heavy alcohol consumption, defined as >= 350-420 g
      alcohol/week. Despite introduction of a standardized reference measurement
      technique, widespread use of CDT remains limited due to low sensitivity. The aim
      of this study was to determine the factors that affect diagnostic sensitivity in
      patients with sustained heavy alcohol intake. METHODS: Patients with a self
      reported history of sustained heavy alcohol consumption were recruited from the
      hepatology outpatient department or medical wards. Each patient was interviewed
      with a validated structured questionnaire of alcohol consumption and CDT analysis
      using the standardized reference measurement technique with high performance
      liquid chromatography was performed on serum collected at time of interview.
      RESULTS: 52 patients were recruited: 19 from the hepatology outpatient department
      and 33 from general medical wards. Median alcohol intake was 1013 (range 366
      5880) g/week over the preceding two week period. 26 patients had a diagnostic CDT
      based on a threshold value of %CDT > 1.7 indicating heavy alcohol consumption,
      yielding a sensitivity of 50%. Overweight/obesity (defined as body mass index
      (BMI) >= 25 kg/m2 in Caucasians and >= 23.0 kg/m2 in Asians), female gender and
      presence of cirrhosis were independently associated with non-diagnostic %CDT (<=
      1.7). CONCLUSIONS: CDT has limited sensitivity as a biomarker of heavy alcohol
      consumption. Caution should be applied when ordering and interpreting %CDT
      results, particularly in women, patients with cirrhosis and those with an
      elevated BMI.

PMID- 24885511
TI  - Atypical language organization in temporal lobe epilepsy revealed by a passive
      semantic paradigm.
AB  - BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is the most common type of focal
      epilepsy in adults and can be successfully cured by surgery. One of the main
      complications of this surgery however is a decline in language abilities. The
      magnitude of this decline is related to the degree of language lateralization to
      the left hemisphere. Most fMRI paradigms used to determine language dominance in
      epileptic populations have used active language tasks. Sometimes, these paradigms
      are too complex and may result in patient underperformance. Only a few studies
      have used purely passive tasks, such as listening to standard speech. METHODS: In
      the present study we characterized language lateralization in patients with MTLE
      using a rapid and passive semantic language task. We used functional magnetic
      resonance imaging (fMRI) to study 23 patients [12 with Left (LMTLE), 11 with
      Right mesial temporal lobe epilepsy (RMTLE)] and 19 healthy right-handed controls
      using a 6 minute long semantic task in which subjects passively listened to
      groups of sentences (SEN) and pseudo sentences (PSEN). A lateralization index
      (LI) was computed using a priori regions of interest of the temporal lobe.
      RESULTS: The LI for the significant contrasts produced activations for all
      participants in both temporal lobes. 81.8% of RMTLE patients and 79% of healthy
      individuals had a bilateral language representation for this particular task.
      However, 50% of LMTLE patients presented an atypical right hemispheric dominance
      in the LI. More importantly, the degree of right lateralization in LMTLE patients
      was correlated with the age of epilepsy onset. CONCLUSIONS: The simple, rapid,
      non-collaboration dependent, passive task described in this study, produces a
      robust activation in the temporal lobe in both patients and controls and is
      capable of illustrating a pattern of atypical language organization for LMTLE
      patients. Furthermore, we observed that the atypical right-lateralization
      patterns in LMTLE patients was associated to earlier age at epilepsy onset. These
      results are in line with the idea that early onset of epileptic activity is
      associated to larger neuroplastic changes.

PMID- 24885512
TI  - V30 as a predictor for radiation-induced hypothyroidism: a dosimetric analysis in
      patients who received radiotherapy to the neck.
AB  - INTRODUCTION: The purpose of this study is to evaluate the possible predictors of
      thyroid disorders after neck radiotherapy, with a focus on radiation dose-volume
      factors. METHODS: Thyroid function was measured in 100 patients who had received
      radiotherapy to the neck, including the thyroid. All radiation-induced thyroid
      dysfunctions were determined with an endpoint of abnormal thyroid stimulating
      hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4) and thyroid
      peroxidase antibodies and (TPA). The total volume of the thyroid, mean radiation
      dose to the thyroid (Dmean) and thyroid volume percentage that received radiation
      doses of 10-50 Gy (V10-V50) were calculated in all patients. The evaluated risk
      factors for thyroid dysfunction included dose-volume parameters, sex, age,
      previous surgery, chemotherapy and comorbidity. RESULTS: There were 52 patients
      with hypothyroidism and V30 (p = 0.03), thyroid volume (p = 0.01) and Dmean (p =
      0.03) appeared to be correlated with hypothyroidism in univariate analysis.
      However, there was not association found in multivariate analysis for these
      factors. CONCLUSIONS: Thyroid disorders after radiation therapy to the neck still
      represent a clinically underestimated problem. V30 may be a useful tool for
      evaluating the risk of hypothyroidism when determining an individual patient's
      treatment.

PMID- 24885514
TI  - Let's Blog About Health! Exploring the Persuasiveness of a Personal HIV Blog
      Compared to an Institutional HIV Website.
AB  - On HIV blogs, people living with HIV share their intimate thoughts and
      experiences with the world in the form of personal online diaries. While previous
      research investigated the reasons why patients engage in blogging activities, the
      effects of such diaries on nondiseased recipients are largely unexplored.
      Following an experimental design, this study (n = 261) tested whether a one-time
      exposure to a personal HIV blog has greater persuasive effects on its readers
      than an institutional HIV website providing the same content. Results showed that
      although source credibility was perceived as higher when reading the HIV website
      from an official institution, blog readers had more positive attitudes and a
      higher self-efficacy toward condom use than website readers. Implications for
      health message design are discussed. 

PMID- 24885515
TI  - CuI-catalyzed C-N bond formation and cleavage for the synthesis of
      benzimidazo[1,2-a]quinazoline derivatives.
AB  - A copper(I)-catalyzed domino reaction of N-(2-benzimidazolyl)-2-aminobenzamide
      and 2-halogenated benzaldehyde has been studied. The procedure is based on a
      sequential CuI-catalyzed Ullmann reaction (C-N bond formation) and two bond
      cleavage reactions and provides an efficient strategy for the synthesis of
      benzimidazo[1,2-a]quinazolines catalyzed by CuI/L-proline.

PMID- 24885513
TI  - A novel approach to identify driver genes involved in androgen-independent
      prostate cancer.
AB  - BACKGROUND: Insertional mutagenesis screens have been used with great success to
      identify oncogenes and tumor suppressor genes. Typically, these screens use
      gammaretroviruses (gammaRV) or transposons as insertional mutagens. However,
      insertional mutations from replication-competent gammaRVs or transposons that
      occur later during oncogenesis can produce passenger mutations that do not drive
      cancer progression. Here, we utilized a replication-incompetent lentiviral vector
      (LV) to perform an insertional mutagenesis screen to identify genes in the
      progression to androgen-independent prostate cancer (AIPC). METHODS: Prostate
      cancer cells were mutagenized with a LV to enrich for clones with a selective
      advantage in an androgen-deficient environment provided by a dysregulated gene(s)
      near the vector integration site. We performed our screen using an in vitro AIPC
      model and also an in vivo xenotransplant model for AIPC. Our approach identified
      proviral integration sites utilizing a shuttle vector that allows for rapid
      rescue of plasmids in E. coli that contain LV long terminal repeat (LTR)
      chromosome junctions. This shuttle vector approach does not require PCR
      amplification and has several advantages over PCR-based techniques. RESULTS:
      Proviral integrations were enriched near prostate cancer susceptibility loci in
      cells grown in androgen-deficient medium (p < 0.001), and five candidate genes
      that influence AIPC were identified; ATPAF1, GCOM1, MEX3D, PTRF, and TRPM4.
      Additionally, we showed that RNAi knockdown of ATPAF1 significantly reduces
      growth (p < 0.05) in androgen-deficient conditions. CONCLUSIONS: Our approach has
      proven effective for use in PCa, identifying a known prostate cancer gene, PTRF,
      and also several genes not previously associated with prostate cancer. The
      replication-incompetent shuttle vector approach has broad potential applications
      for cancer gene discovery, and for interrogating diverse biological and disease
      processes.

PMID- 24885516
TI  - Dynamic photoinhibition exhibited by red coralline algae in the Red Sea.
AB  - BACKGROUND: Red coralline algae are critical components of tropical reef systems,
      and their success and development is, at least in part, dependent on
      photosynthesis. However, natural variability in the photosynthetic
      characteristics of red coralline algae is poorly understood. This study
      investigated diurnal variability in encrusting Porolithon sp. and free-living
      Lithophyllum kotschyanum. Measured parameters included: photosynthetic
      characteristics, pigment composition, thallus reflectance and intracellular
      concentrations of dimethylsulphoniopropionate (DMSP), an algal antioxidant that
      is derived from methionine, an indirect product of photosynthesis. L. kotschyanum
      thalli were characterised by a bleached topside and a pigmented underside.
      RESULTS: Minimum saturation intensity and intracellular DMSP concentrations in
      Porolithon sp. were characterised by significant diurnal patterns in response to
      the high-light regime. A smaller diurnal pattern in minimum saturation intensity
      in the topside of L. kotschyanum was also evident. The overall reflectance of the
      topside of L. kotschyanum also exhibited a diurnal pattern, becoming increasingly
      reflective with increasing ambient irradiance. The underside of L. kotschyanum,
      which is shaded from ambient light exposure, exhibited a much smaller diurnal
      variability. CONCLUSIONS: This study highlights a number of dynamic
      photoinhibition strategies adopted by coralline algae, enabling them to tolerate,
      rather than be inhibited by, the naturally high irradiance of tropical reef
      systems; a factor that may become more important in the future under global
      change projections. In this context, this research has significant implications
      for tropical reef management planning and conservation monitoring, which, if
      natural variability is not taken into account, may become flawed. The information
      provided by this research may be used to inform future investigations into the
      contribution of coralline algae to reef accretion, ecosystem service provision
      and palaeoenvironmental reconstruction.

PMID- 24885517
TI  - Evaluating the possibility of detecting evidence of positive selection across
      Asia with sparse genotype data from the HUGO Pan-Asian SNP Consortium.
AB  - BACKGROUND: The HUGO Pan-Asian SNP Consortium (PASNP) has generated a genetic
      resource of almost 55,000 autosomal single nucleotide polymorphisms (SNPs) across
      more than 1,800 individuals from 73 urban and indigenous populations in Asia.
      This has offered valuable insights into the correlation between the genetic
      ancestry of these populations with major linguistic systems and geography. Here,
      we attempt to understand whether adaptation to local climate, diet and
      environment partly explains the genetic variation present in these populations by
      investigating the genomic signatures of positive selection. RESULTS: To evaluate
      the impact to the selection analyses due to the considerably lower SNP density as
      compared to other population genetics resources such as the International HapMap
      Project (HapMap) or the Singapore Genome Variation Project, we evaluated the
      extent of haplotype phasing switch errors and the consistency of selection
      signals from three haplotype-based approaches (iHS, XP-EHH, haploPS) when the
      HapMap data is thinned to a similar density as PASNP. We subsequently applied
      haploPS to detect and characterize positive selection in the PASNP populations,
      identifying 59 genomics regions that were selected in at least one PASNP
      populations. A cluster analysis on the basis of these 59 signals showed that
      indigenous populations such as the Negrito from Malaysia and Philippines, the
      China Hmong, and the Taiwan Ami and Atayal shared more of these signals. We also
      reported evidence of a positive selection signal encompassing the beta globin
      gene in the Taiwan Ami and Atayal that was distinct from the signal in the HapMap
      Africans, suggesting the possibility of convergent evolution at this locus due to
      malarial selection. CONCLUSIONS: We established that the lower SNP content of the
      PASNP data conferred weaker ability to detect signatures of positive selection,
      but the availability of the new approach haploPS retained modest power. Out of
      all the populations in PASNP, we identified only 59 signals, suggesting a strong
      need for high-density population-level genotyping data or sequencing data in
      order to achieve a comprehensive survey of positive selection in Asian
      populations.

PMID- 24885518
TI  - Small-sized polymeric micelles incorporating docetaxel suppress distant
      metastases in the clinically-relevant 4T1 mouse breast cancer model.
AB  - BACKGROUND: The small size of ultra-small nanoparticles makes them suitable for
      lymphatic delivery, and many recent studies have examined their role in anti
      metastasis therapy. However, the anti-metastatic efficacy of small-sized
      nanocarriers loaded with taxanes such as docetaxel has not yet been investigated
      in malignant breast cancer. METHODS: We encapsulated docetaxel using poly(D,L
      lactide)1300-b-(polyethylene glycol-methoxy)2000 (mPEG2000-b-PDLLA1300) to
      construct polymeric micelles with a mean diameter of 16.76 nm (SPM). Patient-like
      4T1/4T1luc breast cancer models in Balb/c mice, with resected and unresected
      primary tumors, were used to compare the therapeutic efficacies of SPM and free
      docetaxel (Duopafei) against breast cancer metastasis using bioluminescent
      imaging, lung nodule examination, and histological examination. RESULT: SPM
      showed similar efficacy to Duopafei in terms of growth suppression of primary
      tumors, but greater chemotherapeutic efficacy against breast cancer metastasis.
      In addition, lung tissue inflammation was decreased in the SPM-treated group,
      while many tumor cells and neutrophils were found in the Duopafei-treated group.
      CONCLUSION: Small-sized mPEG2000-b-PDLLA1300 micelles could provide an enhanced
      method of docetaxel delivery in breast cancer metastasis, and may represent a
      valid chemotherapeutic strategy in breast cancer patients with resected primary
      tumors.

PMID- 24885519
TI  - Efficacy of intraoperative epidural steroids in lumbar discectomy: a systematic
      review.
AB  - BACKGROUND: This study is a descriptive review of the literature aimed at
      examining the efficacy of the use of intraoperative epidural steroids in lumbar
      disc surgery, a matter that remains controversial. METHODS: The relevant clinical
      trials were selected from databases and reviewed. The methodological quality of
      each included study was assessed and graded for perceived risk of bias. All the
      documented significant and non-significant findings were collected. Our outcome
      targets were reduction in postoperative pain scores, consumption of analgesia,
      duration of hospital stay and no increase in complication rates. The variation in
      the timing of postoperative pain assessments necessitated grouping the outcome
      into three postoperative stages; early: 0 to 2 weeks, intermediate: more than 2
      weeks to 2 months and late: more than 2 months to 1 year. RESULTS: Sixteen trials
      that were published from 1990 to 2012 were eligible. At least one significant
      reduction in pain score was reported in nine of the eleven trials that examined
      pain in the early stage, in four of the seven trials that examined pain in the
      intermediate stage and in two of the eight trials that examined pain in the late
      stage. Seven of the nine trials that looked at consumption of postoperative
      analgesia reported significant reduction while six of the ten trails that
      examined the duration of hospital stay reported significant reduction. None of
      the trials reported a significant increase of steroid-related complications.
      CONCLUSIONS: There is relatively strong evidence that intraoperative epidural
      steroids are effective in reducing pain in the early stage and reducing
      consumption of analgesia. There is also relatively strong evidence that they are
      ineffective in reducing pain in the late stage and in reducing duration of
      hospital stay. The evidence for their effectiveness in reducing pain in the
      intermediate stage is considered relatively weak. The heterogeneity between the
      trials makes it difficult to make undisputed conclusions and it indicates the
      need for a large multicenter trial with validated outcome measures that are
      recorded at fixed time intervals.

PMID- 24885520
TI  - The genetic architecture of constitutive and induced trichome density in two new
      recombinant inbred line populations of Arabidopsis thaliana: phenotypic
      plasticity, epistasis, and bidirectional leaf damage response.
AB  - BACKGROUND: Herbivory imposes an important selective pressure on plants. In
      Arabidopsis thaliana leaf trichomes provide a key defense against insect
      herbivory; however, trichome production incurs a fitness cost in the absence of
      herbivory. Previous work on A. thaliana has shown an increase in trichome density
      in response to leaf damage, suggesting a mechanism by which the cost associated
      with constitutively high trichome density might be mitigated; however, the
      genetic basis of trichome density induction has not been studied. RESULTS: Here,
      we describe the mapping of quantitative trait loci (QTL) for constitutive and
      damage induced trichome density in two new recombinant inbred line populations of
      A. thaliana; mapping for constitutive and induced trichome density also allowed
      for the investigation of damage response (plasticity) QTL. Both novel and
      previously identified QTL for constitutive trichome density and the first QTL for
      induced trichome density and response are identified. Interestingly, two of the
      four parental accessions and multiple RILs in each population exhibited lower
      trichome density following leaf damage, a response not previously described in A.
      thaliana. Importantly, a single QTL was mapped for the response phenotype and
      allelic variation at this locus appears to determine response trajectory in RILs.
      The data also show that epistatic interactions are a significant component of the
      genetic architecture of trichome density. CONCLUSIONS: Together, our results
      provide further insights into the genetic architecture of constitutive trichome
      density and new insights into induced trichome density in A. thaliana
      specifically and to our understanding of the genetic underpinnings of natural
      variation generally.

PMID- 24885522
TI  - LincSNP: a database of linking disease-associated SNPs to human large intergenic
      non-coding RNAs.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have successfully identified a
      large number of single nucleotide polymorphisms (SNPs) that are associated with a
      wide range of human diseases. However, many of these disease-associated SNPs are
      located in non-coding regions and have remained largely unexplained. Recent
      findings indicate that disease-associated SNPs in human large intergenic non
      coding RNA (lincRNA) may lead to susceptibility to diseases through their effects
      on lincRNA expression. There is, therefore, a need to specifically record these
      SNPs and annotate them as potential candidates for disease. DESCRIPTION: We have
      built LincSNP, an integrated database, to identify and annotate disease
      associated SNPs in human lincRNAs. The current release of LincSNP contains
      approximately 140,000 disease-associated SNPs (or linkage disequilibrium SNPs),
      which can be mapped to around 5,000 human lincRNAs, together with their
      comprehensive functional annotations. The database also contains annotated,
      experimentally supported SNP-lincRNA-disease associations and disease-associated
      lincRNAs. It provides flexible search options for data extraction and searches
      can be performed by disease/phenotype name, SNP ID, lincRNA name and chromosome
      region. In addition, we provide users with a link to download all the data from
      LincSNP and have developed a web interface for the submission of novel identified
      SNP-lincRNA-disease associations. CONCLUSIONS: The LincSNP database aims to
      integrate disease-associated SNPs and human lincRNAs, which will be an important
      resource for the investigation of the functions and mechanisms of lincRNAs in
      human disease. The database is available at http://bioinfo.hrbmu.edu.cn/LincSNP.

PMID- 24885521
TI  - Toxoplasma gondii merozoite gene expression analysis with comparison to the life
      cycle discloses a unique expression state during enteric development.
AB  - BACKGROUND: Considerable work has been carried out to understand the biology of
      tachyzoites and bradyzoites of Toxoplasma gondii in large part due to in vitro
      culture methods for these stages. However, culturing methods for stages that
      normally develop in the gut of the definitive felid host, including the merozoite
      and sexual stages, have not been developed hindering the ability to study a large
      portion of the parasite's life cycle. Here, we begin to unravel the molecular
      aspects of enteric stages by providing new data on merozoite stage gene
      expression. RESULTS: To profile gene expression differences in enteric stages we
      harvested merozoites from the intestine of infected cats and hybridized mRNA to
      the Affymetrix Toxoplasma GeneChip. We analyzed the merozoite data in context of
      the life cycle by comparing it to previously published data for the oocyst,
      tachyzoite, and bradyzoite stages. Principal component analysis highlighted the
      unique profile of merozoites, placing them approximately half-way on a continuum
      between the tachyzoite/bradyzoite and oocyst samples. Prior studies have shown
      that antibodies to surface antigen one (SAG1) and many dense granule proteins do
      not label merozoites: our microarray data confirms that these genes were not
      expressed at this stage. Also, the expression for many rhoptry and microneme
      proteins was drastically reduced while the expression for many surface antigens
      was increased at the merozoite stage. Gene Ontology and KEGG analysis revealed
      that genes involved in transcription/translation and many metabolic pathways were
      upregulated at the merozoite stage, highlighting unique growth requirements of
      this stage. To functionally test these predictions, we demonstrated that an
      upstream promoter region of a merozoite specific gene was sufficient to control
      expression in merozoites in vivo. CONCLUSIONS: Merozoites are the first
      developmental stage in the coccidian cycle that takes place within the gut of the
      definitive host. The data presented here describe the global gene expression
      profile of the merozoite stage and the creation of transgenic parasite strains
      that show stage-specific expression of reporter genes in the cat intestine. These
      data and reagents will be useful in unlocking how the parasite senses and
      responds to the felid gut environment to initiate enteric development.

PMID- 24885523
TI  - A novel mutation in C5L2 gene was associated with hyperlipidemia and retinitis
      pigmentosa in a Chinese family.
AB  - BACKGROUND: Previous studies indicated that hyperlipidemia was associated with
      retinitis pigmentosa (RP). We aimed to identify the mutations in the C5L2 gene
      which was reported to be associated with hyperlipidemia in a Chinese family with
      (RP). METHODS: The Proband from the family was screened for mutations in the C5L2
      gene that was known to cause hyperlipidemia. Cosegregation analysis was performed
      in the available family members. Linkage analysis was performed for one missense
      mutation to calculate the likelihood of its pathogenicity. One hundred and fifty
      unrelated, healthy Chinese subjects were screened to exclude nonpathogenic
      polymorphisms. RESULTS: By direct sequencing method, we identified a novel
      mutation (Thr196Asn) in C5L2 gene. In this family, each affected family members
      with RP showed a heterozygous mutation in the C5L2 gene. And all the carriers
      with heterozygous mutation have increased serum lipid levels in this family.
      CONCLUSIONS: The present study has extended the mutation spectrum of C5L2, and
      Thr196Asn mutations in C5L2 were associated with RP and serum lipid levels.

PMID- 24885524
TI  - Patients with persistent medically unexplained physical symptoms: a descriptive
      study from Norwegian general practice.
AB  - BACKGROUND: Further research on effective interventions for patients with
      peristent Medically Unexplained Physical Symptoms (MUPS) in general practice is
      needed. Prevalence estimates of such patients are conflicting, and other
      descriptive knowledge is needed for development and evaluation of effective
      future interventions. In this study, we aimed to estimate the consultation
      prevalence of patients with persistent MUPS in general practice, including
      patients' characteristics and symptom pattern, employment status and use of
      social benefits, and the general practitioners' (GPs) management strategy.
      METHOD: During a four-week period the participating Norwegian GPs (n=84)
      registered all consultations with patients who met a strict definition of MUPS
      (>3 months duration and function loss), using a questionnaire with simple tick
      off questions. Analyses were performed with descriptive statistics for all
      variables and split analysis on gender and age. RESULTS: The GPs registered 526
      patients among their total of 17 688 consultations, giving a consultation
      prevalence of persistent MUPS of 3%. The mean age of patients was 46 years, and
      399 (76%) were women. The most frequent group of symptoms was musculoskeletal
      problems, followed by asthenia/fatigue. There was no significant gender
      difference in symptom pattern. Almost half of the patients were currently working
      (45%), significantly more men. The major GP management strategy was supportive
      counseling. CONCLUSION: A consultation prevalence rate of 3% implies that
      patients with persistent MUPS are common in general practice. Our study disclosed
      heterogeneity among the patients such as differences in employment status, which
      emphasizes the importance of personalized focus rather than unsubstantiated
      stereotyping of "MUPS patients" as a group.

PMID- 24885525
TI  - Selected parameters of the corneal deformation in the Corvis tonometer.
AB  - INTRODUCTION: Contemporary ophthalmology knows many methods of measuring
      intraocular pressure, namely the methods of non-contact and impression
      applanation tonometry. In non-contact applanation tonometers, e.g. the Corvis,
      the corneal flattening is caused by an air puff. Image registration of the
      corneal deflection performed by a tonometer enables to determine other
      interesting biomechanical parameters of the eye, which are not available in the
      tonometer. The measurement of new selected parameters is presented in this paper.
      MATERIAL AND METHOD: Images with an M * N * I resolution of 200 * 576 * 140
      pixels were acquired from the Corvis device in the source recording format *.cst.
      A total of 13'400 2D images of patients examined routinely in the Clinical
      Department of Ophthalmology, in District Railway Hospital in Katowice, Poland,
      were analysed in accordance with the Declaration of Helsinki. A new method has
      been proposed for the analysis of corneal deflection images in the Corvis
      tonometer with the use of the Canny edge detection method, mathematical
      morphology methods and context-free operations. RESULTS: The resulting image
      analysis tool allows determination of the response of the cornea and the entire
      eyeball to an air puff. The paper presents the method that enables the
      measurement of the amplitude of curvature changes in the frequency range from 150
      to 500 Hz and automatic designation of the eyeball movement direction. The
      analysis of these data resulted in 3 new features of dynamics of the eye reaction
      to an air puff. Classification of these features enabled to propose 4 classes of
      deformation. The proposed algorithm allows to obtain reproducible results fully
      automatically at a time of 5 s per patient using the Core i5 CPU M460 @ 2.5GHz
      4GB of RAM. CONCLUSIONS: The paper presents the possibility of using a profiled
      algorithm of image analysis, proposed by the authors, to measure additional
      cornea deformation parameters. The new tool enables automatic measurement of the
      additional new parameters when using the Corvis tonometer. A detailed clinical
      examination based on this method will be presented in subsequent papers.

PMID- 24885527
TI  - Autonomous exoskeleton reduces metabolic cost of human walking during load
      carriage.
AB  - BACKGROUND: Many soldiers are expected to carry heavy loads over extended
      distances, often resulting in physical and mental fatigue. In this study, the
      design and testing of an autonomous leg exoskeleton is presented. The aim of the
      device is to reduce the energetic cost of loaded walking. In addition, we present
      the Augmentation Factor, a general framework of exoskeletal performance that
      unifies our results with the varying abilities of previously developed
      exoskeletons. METHODS: We developed an autonomous battery powered exoskeleton
      that is capable of providing substantial levels of positive mechanical power to
      the ankle during the push-off region of stance phase. We measured the metabolic
      energy consumption of seven subjects walking on a level treadmill at 1.5 m/s,
      while wearing a 23 kg vest. RESULTS: During the push-off portion of the stance
      phase, the exoskeleton applied positive mechanical power with an average across
      the gait cycle equal to 23 +/- 2 W (11.5 W per ankle). Use of the autonomous leg
      exoskeleton significantly reduced the metabolic cost of walking by 36 +/- 12 W,
      which was an improvement of 8 +/- 3% (p = 0.025) relative to the control
      condition of not wearing the exoskeleton. CONCLUSIONS: In the design of leg
      exoskeletons, the results of this study highlight the importance of minimizing
      exoskeletal power dissipation and added limb mass, while providing substantial
      positive power during the walking gait cycle.

PMID- 24885526
TI  - Adult attention-deficit/hyperactivity disorder and nicotine use: a qualitative
      study of patient perceptions.
AB  - BACKGROUND: Adult Attention-Deficit/Hyperactivity Disorder (ADHD) is associated
      with high rates of comorbid substance use disorders, and cigarette smoking has a
      particularly high prevalence in this population. However, there is an ongoing
      debate as to whether this tobacco use is an attempt at "self-medication" or due
      to behavioral disinhibition. There is a surprising lack of qualitative studies
      that investigate the subjective perceptions of adults with ADHD regarding
      cigarette smoking. The present study was designed to fill this gap in the
      literature. METHODS: We recruited twelve adult patients with ADHD and comorbid
      tobacco use from our ADHD consultation service, an outpatient facility of the
      Zurich University Psychiatric Hospital. Subjects were interviewed using
      qualitative methodology, and Mayring's qualitative content analysis was used to
      evaluate findings. RESULTS: We identified two explanatory models linking ADHD and
      tobacco use: smoking as an attempt at self-medication and "smoking as a social
      behavior". On one hand, subjects considered tobacco a therapeutic aid, reporting
      positive effects on "inner tension" and cognitive function, and noted possible
      antidepressant properties as well. On the other hand, subjects considered smoking
      to enhance social functioning and to have a positive impact on interpersonal
      relationships. The majority believed that stimulant medications offered only a
      transient decrease in patterns of tobacco use because their ability to reduce
      nicotine cravings wore off quickly. Others believed that stimulants had no effect
      or even reinforced cigarette use. CONCLUSIONS: Participants had different views
      about the link between cigarette smoking and ADHD. While the majority thought of
      nicotine as a sort of therapy, viewing smoking as a way to self-medicate symptoms
      of ADHD, motivations for nicotine use were also related to self-image, desire to
      belong to a peer-group, and a drive to undermine perceived social norms.
      Ultimately, these findings can be used by clinicians to improve treatment
      alliance and collaboration.

PMID- 24885528
TI  - Total synthesis of (-)-goniomitine.
AB  - The total synthesis of (-)-goniomitine has been accomplished in 11 steps starting
      from commercially available diethyl l-malate. The synthesis features a chiral
      pool approach to prepare the chiral C-9 unit containing a quaternary carbon
      center, an Ir-catalyzed C-H borylation to synthesize the 2-indoleboronic acid
      pinacol ester, and a Suzuki reaction to couple together the two key
      intermediates. Notably, the high degree of convergence of this strategy makes it
      particularly amenable to the total synthesis of other aspidosperma family natural
      products. 

PMID- 24885529
TI  - Chikungunya antibodies detected in non-human primates and rats in three Indian
      Ocean islands after the 2006 ChikV outbreak.
AB  - The role of terrestrial vertebrates in the epidemiology of chikungunya disease is
      poorly understood. We evaluated their exposure and amplification role during the
      2006 chikungunya outbreak in the Indian Ocean. Blood samples were collected from
      18 mammalian and reptile species from Reunion Island, Mauritius and Mayotte.
      Among the 1051 samples serologically tested for chikungunya virus (CHIKV), two
      crab-eating macaques (Macaca fascicularis) and two ship rats (Rattus rattus)
      proved to be exposed to CHIKV. CHIKV RNA was not detected in 791 analyzed sera.
      Our results confirm the preferential infection of simian primates and suggest
      that other vertebrates played a poor or no role in CHIKV transmission during the
      2006 outbreak.

PMID- 24885530
TI  - Phylogeny of Mycoplasma bovis isolates from Hungary based on multi locus sequence
      typing and multiple-locus variable-number tandem repeat analysis.
AB  - BACKGROUND: Mycoplasma bovis is an important pathogen causing pneumonia, mastitis
      and arthritis in cattle worldwide. As this agent is primarily transmitted by
      direct contact and spread through animal movements, efficient genotyping systems
      are essential for the monitoring of the disease and for epidemiological
      investigations. The aim of this study was to compare and evaluate the multi locus
      sequence typing (MLST) and the multiple-locus variable-number tandem repeat
      (VNTR) analysis (MLVA) through the genetic characterization of M. bovis isolates
      from Hungary. RESULTS: Thirty one Hungarian M. bovis isolates grouped into two
      clades by MLST. Two strains had the same sequence type (ST) as reference strain
      PG45, while the other twenty nine Hungarian isolates formed a novel clade
      comprising five subclades. Isolates originating from the same herds had the same
      STs except for one case. The same isolates formed two main clades and several
      subclades and branches by MLVA. One clade contained the reference strain PG45 and
      three isolates, while the other main clade comprised the rest of the strains.
      Within-herd strain divergence was also detected by MLVA. Little congruence was
      found between the results of the two typing systems. CONCLUSIONS: MLST is
      generally considered an intermediate scale typing method and it was found to be
      discriminatory among the Hungarian M. bovis isolates. MLVA proved to be an
      appropriate fine scale typing tool for M. bovis as this method was able to
      distinguish closely related strains isolated from the same farm. We recommend the
      combined use of the two methods for the genotyping of M. bovis isolates. Strains
      have to be characterized first by MLST followed by the fine scale typing of
      identical STs with MLVA.

PMID- 24885531
TI  - Lipocalin 2 in cerebrospinal fluid as a marker of acute bacterial meningitis.
AB  - BACKGROUND: Early differential diagnosis between acute bacterial and viral
      meningitis is problematic. We aimed to investigate whether the detection of
      lipocalin 2, a protein of the acute innate immunity response, may be used as a
      marker for acute bacterial meningitis. METHODS: Transgenic mice expressing the
      human transferrin were infected by intraperitoneal route and were imaged.
      Cerebrospinal fluid (CSF) was sampled up to 48hours post- infection to measure
      lipocalin 2. We also tested a collection of 90 and 44 human CSF with confirmed
      acute bacterial or acute viral meningitis respectively. RESULTS: Lipocalin 2 was
      detected after 5 h in CSF during experimental infection in mice. Lipocalin 2
      levels were significantly higher (p < 0.0001) in patients with confirmed acute
      bacterial meningitis (mean 125 pg/mL, range 106-145 pg/mL) than in patients with
      acute viral meningitis (mean 2 pg/mL, range 0-6 pg/mL) with a sensitivity of 81%,
      a specificity of 93%, a positive predictive value of 96% and a negative
      predictive value of 71% in diagnosing acute bacterial meningitis. CONCLUSIONS:
      Increased levels of lipocalin 2 in cerebrospinal fluid may discriminate between
      acute bacterial and viral meningitis in patients with clinical syndrome of
      meningitis.

PMID- 24885532
TI  - Prevalence of domestic violence during pregnancy and related risk factors: a
      cross-sectional study in southern Sweden.
AB  - BACKGROUND: Domestic violence during pregnancy is a serious public health issue
      which threatens maternal and foetal health outcomes. The aim of the study was to
      explore prevalence of domestic violence among pregnant women in southern Sweden
      (Scania) and to explore associations with background factors, as symptoms of
      depression and sense of coherence. METHODS: This study has a cross-sectional
      design and is the first part of a longitudinal, cohort study. Inclusion criteria
      were women >= 18 years, registered at antenatal care when pregnant and who
      understand and write Swedish or English. Questionnaires were collected
      prospectively at seventeen antenatal care receptions situated in the two cities
      and six smaller municipalities in Scania. Statistical analyses were done using
      descriptive statistics, chi-square tests, bivariate logistic regression and
      multiple regression with Odds ratios (OR) and 95% confidence intervals (95% CI).
      RESULTS: Study sample included 1939 women. History of violence was reported by
      39.5% (n =761) women. Significant differences were obtained between the groups
      with or without history of violence regarding being single/living apart,
      unemployment, financial distress, smoking/snuffing, unintended pregnancy as well
      as history of miscarriage/legalised abortion (p < 0.001). Experience of domestic
      violence during pregnancy regardless of type or level of abuse was 1.0% (n = 18);
      history of physical abuse by actual intimate partner was 2.2% (n = 42). History
      of violence was the strongest risk factor associated with domestic violence
      during pregnancy, where all women (n = 18) exposed reported history of violence
      (p < 0.001). Several symptoms of depression (adjusted for low socio-economic
      status, miscarriage/abortion, single/living apart, lack of sleep, unemployment,
      age and parity) were associated with a 7.0 fold risk of domestic violence during
      pregnancy (OR 7.0; 95% CI: 1.9-26.3). CONCLUSIONS: The reported prevalence of
      domestic violence during pregnancy in southwest Sweden is low. However, a
      considerable proportion of women reported history of living in a violent
      relationship. Both history of violence and the presence of several depressive
      symptoms detected in early pregnancy may indicate that the woman also is exposed
      to domestic violence during pregnancy. Increased attention to this vulnerable
      group of women is needed to improve maternal and child health.

PMID- 24885533
TI  - The factorial and discriminant validity of the German version of the Post
      traumatic Growth Inventory in stroke patients.
AB  - Post-traumatic growth (PTG) is the experience of positive changes that can follow
      a traumatic event. The current study examined the factorial as well as the
      discriminant validity of the German version of the Post-traumatic Growth
      Inventory (PTGI-G) in stroke patients. A total of 188 adult stroke patients
      (63.3% male; median age 69 years) completed the PTGI-G and the German version of
      the Hospital Anxiety and Depression Scale (HADS-D) at the end of their inpatient
      rehabilitation. Confirmatory factor analyses indicate an acceptable model fit of
      both the original five-factor solution as well as a second-order factor model of
      the PTGI-G (CFI > .95; RMSEA < .01). Small and non-significant correlations
      between the PTGI-G subscales and the depression scale of the HADS-D support the
      discriminant validity of the PTGI-G. The PTGI-G appears to be a valid tool in the
      context of stroke research. 

PMID- 24885534
TI  - An aberrant spliced transcript of focal adhesion kinase is exclusively expressed
      in human breast cancer.
AB  - PURPOSE: To clarify the roles of a new aberrantly spliced transcript of FAK that
      lacks exon 26 (denoted -26-exon FAK) in human breast cancers. METHODS:
      Transcripts of FAK expressed in 102 human breast tumor tissues and 52
      corresponding normal tissues were analyzed by RT-PCR and DNA sequencing, as well
      as agarose gel electrophoresis. The cDNA of -26-exon FAK was cloned and expressed
      in MCF-10A cells, and then the kinase activity, cellular localization and
      migration capability of FAK were examined by western blotting, immunofluorescent
      staining and migration assays, respectively. The expression levels of FAK were
      analyzed by western blotting in MCF-7 cells treated with TNF-alpha or in MCF-10A
      cells upon serum deprivation. The MCF-10A cells transfected with a plasmid
      expressing -26-exon FAK were cultured in serum-free medium and cell apoptosis was
      analyzed by flow cytometry. RESULTS: The -26-exon FAK transcript was exclusively
      present in human breast tumor tissues and the encoded protein possessed the same
      kinase activity, cellular localization and cell migration-promoting ability as
      wild-type FAK. In MCF-7 cells treated with TNF-alpha, and in MCF-10A cells upon
      serum deprivation, the -26-exon FAK was resistant to proteolysis while wild-type
      FAK was largely cleaved. In addition, the -26-exon FAK, but not wild-type FAK,
      inhibited cell apoptosis. CONCLUSIONS: The -26-exon FAK transcript, which is
      exclusively expressed in human breast tumor tissues, encodes a protein that
      possesses the same kinase activity and biological function as the wild-type FAK,
      but because it is resistant to the caspase-mediated cleavage that induces the
      proteolysis of the wild-type form, it ultimately prevents apoptosis.

PMID- 24885535
TI  - Characterization of drug resistance associated genetic polymorphisms among
      Plasmodium falciparum field isolates in Ujjain, Madhya Pradesh, India.
AB  - BACKGROUND: Since 2011, artesunate + sulphadoxine-pyrimethamine (ASP), instead of
      chloroquine, has been recommended for treatment of uncomplicated malaria in
      India. In Ujjain, central India, with an annual parasite index <0.1, the
      prevalence of drug-resistant Plasmodium falciparum is unknown. In other parts of
      India chloroquine and sulphadoxine-pyrimethamine-resistant P. falciparum is
      prevalent. The aim of this study was to determine the prevalence of anti-malarial
      drug resistance-associated genetic polymorphisms in P. falciparum collected in
      Ujjain in 2009 and 2010, prior to the introduction of ASP. METHODS: Blood samples
      from 87 patients with P. falciparum mono-infection verified by microscopy were
      collected on filter-paper at all nine major pathology laboratories in Ujjain
      city. Codons Pfcrt 72-76, pfmdr1 1034-1246, pfdhfr 16-185, pfdhps 436-632 and
      pfnhe1 ms4760 haplotypes were identified by sequencing. Pfcrt K76T and pfmdr1
      N86Y were identified by restriction fragment length polymorphism, and pfmdr1 gene
      copy number by real-time PCR. RESULTS: Sulphadoxine-pyrimethamine resistance
      associated pfdhfr 108 N and 59R alleles were found in 75/78 (96%) and 70/78 (90%)
      samples, respectively, and pfdhps 437G was found in 7/77 (9%) samples. Double
      mutant pfdhfr 59R + 108 N were found in 62/76 (82%) samples. Triple mutant pfdhfr
      59R + 108 N and pfdhps 437G were found in 6/76 (8%) samples. Chloroquine
      resistance-associated pfcrt 76 T was found in 82/87 (94%). The pfcrt 72-76
      haplotypes found were: 80/84 (95%) SVMNT, 3/84 (4%) CVMNK and 1/84 (1%) CVMNT.
      Pfmdr1 N86 and 86Y were identified in 70/83 (84%) and 13/83 (16%) samples,
      respectively. Pfmdr1 S1034 + N1042 + D1246 were identified together in 70/72
      (97%) of successfully sequenced samples. One pfmdr1 gene copy was found in 74/75
      (99%) successfully amplified samples. CONCLUSION: This is the first
      characterization of key anti-malarial drug resistance-associated genetic markers
      among P. falciparum collected in Ujjain, Madhya Pradesh, India. The results
      indicate that the efficacy of standard dose chloroquine at the time of the study
      was likely to be poor, whereas ASP was likely to be efficacious, supporting the
      changed drug treatment policy. However, P. falciparum with reduced susceptibility
      to sulphadoxine-pyrimethamine is highly prevalent, highlighting the need for
      continuous surveillance of ASP efficacy in the study area.

PMID- 24885536
TI  - Expression of fibroblast specific protein-1 in pleural tuberculosis and its
      clinical biological significance.
AB  - BACKGROUND: Fibroblast specific protein-1 (S100A4) is related with many fibrotic
      diseases, but its role in the pathogenesis of pleural fibrosis has not been fully
      elucidated. Then we aim to investigate the expression and effect of fibroblast
      specific protein-1 (S100A4) in pleural tuberculosis and, subsequently, pleural
      fibrosis. METHODS: The expression of S100A4 in pleura was examined in 30 patients
      with pleural tuberculosis and 5 control (disease-free) patients by
      immunohistochemistry using the streptavidin-peroxidase (S-P) conjugated method.
      RESULTS: The expression of S100A4 in pleura was mainly distributed in the nucleus
      and cytoplasm of fibroblasts and vascular endothelial cells, and the positive
      rate was 90.0% (27 out of 30 patients with pleural tuberculosis). There were no
      expressions of S100A4 in the control group. In the pleura of all 30 patients with
      pleural tuberculosis, S100A4 had a higher expression in the two- to eight-week
      duration of the disease. CONCLUSIONS: S100A4 plays an important role in the
      phenotypic transformation of pleural mesothelial cells and the development of
      pleural fibrosis.

PMID- 24885537
TI  - Sexual violence and sub-Saharan migrants in Morocco: a community-based
      participatory assessment using respondent driven sampling.
AB  - BACKGROUND: The European Union contracted Morocco to regulate migration from so
      called "transit migrants" from Morocco to Europe via the European Neighbourhood
      Policy. Yet, international organisations signal that human, asylum and refugee
      rights are not upheld in Morocco and that many sub-Saharan migrants suffer from
      ill-health and violence. Hence, our study aimed at 1) investigating the nature of
      violence that sub-Saharan migrants experience around and in Morocco, 2) assessing
      which determinants they perceive as decisive and 3) formulating prevention
      recommendations. METHODS: Applying Community-Based Participatory Research, we
      trained twelve sub-Saharan migrants as Community Researchers to conduct in-depth
      interviews with peers, using Respondent Driven Sampling. We used Nvivo 8 to
      analyse the data. We interpreted results with Community Researchers and the
      Community Advisory Board and commonly formulated prevention recommendations.
      RESULTS: Among the 154 (60 F-94 M) sub-Saharan migrants interviewed, 90% reported
      cases of multiple victimizations, 45% of which was sexual, predominantly gang
      rape. Seventy-nine respondents were personally victimized, 41 were forced to
      witness how relatives or co-migrants were victimized and 18 others knew of peer
      victimisation. Severe long lasting ill-health consequences were reported while
      sub-Saharan victims are not granted access to the official health care system.
      Perpetrators were mostly Moroccan or Algerian officials and sub-Saharan gang
      leaders who function as unofficial yet rigorous migration professionals at
      migration 'hubs'. They seem to proceed in impunity. Respondents link risk factors
      mainly to their undocumented and unprotected status and suggest that migrant
      communities set-up awareness raising campaigns on risks while legal and policy
      changes enforcing human rights, legal protection and human treatment of migrants
      along with severe punishment of perpetrators are politically lobbied for.
      CONCLUSION: Sub-Saharan migrants are at high risk of sexual victimization and
      subsequent ill-health in and around Morocco. Comprehensive cross-border and multi
      level prevention actions are urgently called for. Given the European
      Neighbourhood Policy, we deem it paramount that the European Union politically
      cares for these migrants' lives and health, takes up its responsibility,
      drastically changes migration regulation into one that upholds human rights
      beyond survival and enforces all authorities involved to restore migrants' lives
      worthy to be lived again.

PMID- 24885538
TI  - Detection of driver metabolites in the human liver metabolic network using
      structural controllability analysis.
AB  - BACKGROUND: Abnormal states in human liver metabolism are major causes of human
      liver diseases ranging from hepatitis to hepatic tumor. The accumulation in
      relevant data makes it feasible to derive a large-scale human liver metabolic
      network (HLMN) and to discover important biological principles or drug-targets
      based on network analysis. Some studies have shown that interesting biological
      phenomenon and drug-targets could be discovered by applying structural
      controllability analysis (which is a newly prevailed concept in networks) to
      biological networks. The exploration on the connections between structural
      controllability theory and the HLMN could be used to uncover valuable information
      on the human liver metabolism from a fresh perspective. RESULTS: We applied
      structural controllability analysis to the HLMN and detected driver metabolites.
      The driver metabolites tend to have strong ability to influence the states of
      other metabolites and weak susceptibility to be influenced by the states of
      others. In addition, the metabolites were classified into three classes:
      critical, high-frequency and low-frequency driver metabolites. Among the
      identified 36 critical driver metabolites, 27 metabolites were found to be
      essential; the high-frequency driver metabolites tend to participate in different
      metabolic pathways, which are important in regulating the whole metabolic
      systems. Moreover, we explored some other possible connections between the
      structural controllability theory and the HLMN, and find that transport reactions
      and the environment play important roles in the human liver metabolism.
      CONCLUSION: There are interesting connections between the structural
      controllability theory and the human liver metabolism: driver metabolites have
      essential biological functions; the crucial role of extracellular metabolites and
      transport reactions in controlling the HLMN highlights the importance of the
      environment in the health of human liver metabolism.

PMID- 24885540
TI  - Health and human rights in eastern Myanmar prior to political transition: a
      population-based assessment using multistaged household cluster sampling.
AB  - BACKGROUND: Myanmar/Burma has received increased development and humanitarian
      assistance since the election in November 2010. Monitoring the impact of foreign
      assistance and economic development on health and human rights requires knowledge
      of pre-election conditions. METHODS: From October 2008-January 2009, community
      based organizations conducted household surveys using three-stage cluster
      sampling in Shan, Kayin, Bago, Kayah, Mon and Tanintharyi areas of Myanmar. Data
      was collected from 5,592 heads of household on household demographics,
      reproductive health, diarrhea, births, deaths, malaria, and acute malnutrition of
      children 6-59 months and women aged 15-49 years. A human rights focused survey
      module evaluated human rights violations (HRVs) experienced by household members
      during the previous year. RESULTS: Estimated infant and under-five rates were 77
      (95% CI 56 to 98) and 139 (95% CI 107 to 171) deaths per 1,000 live births; and
      the crude mortality rate was 13 (95% CI 11 to 15) deaths per thousand persons.
      The leading respondent-reported cause of death was malaria, followed by acute
      respiratory infection and diarrhea, causing 21.2% (95% CI 16.5 to 25.8), 16.6%
      (95% CI 11.8 to 21.4), and 12.3% (95% CI 8.7 to 15.8), respectively. Over a third
      of households suffered at least one human rights violation in the preceding year
      (36.2%; 30.7 to 41.7). Household exposure to forced labor increased risk of death
      among infants (rate ratio (RR) = 2.2; 95% CI 1.1 to 4.4) and children under five
      (RR = 2.1; 95% CI 1.3 to 3.6). The proportion of children suffering from moderate
      to severe acute malnutrition was higher among households that were displaced
      (prevalence ratio (PR) = 3.3; 95% CI 1.9 to 5.6). CONCLUSIONS: Prior to the 2010
      election, populations of eastern Myanmar experienced high rates of disease and
      death and high rates of HRVs. These population-based data provide a baseline that
      can be used to monitor national and international efforts to improve the health
      and human rights situation in the region.

PMID- 24885539
TI  - Comparative genome analysis of pathogenic and non-pathogenic Clavibacter strains
      reveals adaptations to their lifestyle.
AB  - BACKGROUND: The genus Clavibacter harbors economically important plant pathogens
      infecting agricultural crops such as potato and tomato. Although the vast
      majority of Clavibacter strains are pathogenic, there is an increasing number of
      non-pathogenic isolates reported. Non-pathogenic Clavibacter strains isolated
      from tomato seeds are particularly problematic because they affect the current
      detection and identification tests for Clavibacter michiganensis subsp.
      michiganensis (Cmm), which is regulated with a zero tolerance in tomato seed.
      Their misidentification as pathogenic Cmm hampers a clear judgment on the seed
      quality and health. RESULTS: To get more insight in the genetic features linked
      to the lifestyle of these bacteria, a whole-genome sequence of the tomato seed
      borne non-pathogenic Clavibacter LMG 26808 was determined. To gain a better
      understanding of the molecular determinants of pathogenicity, the genome sequence
      of LMG 26808 was compared with that of the pathogenic Cmm strain (NCPPB 382). The
      comparative analysis revealed that LMG 26808 does not contain plasmids pCM1 and
      pCM2 and also lacks the majority of important virulence factors described so far
      for pathogenic Cmm. This explains its apparent non-pathogenic nature in tomato
      plants. Moreover, the genome analysis of LMG 26808 detected sequences from a
      plasmid originating from a member of Enterobacteriaceae/Klebsiella relative.
      Genes received that way and coding for antibiotic resistance may provide a
      competitive advantage for survival of LMG 26808 in its ecological niche.
      Genetically, LMG 26808 was the most similar to the pathogenic Cmm NCPPB 382 but
      contained more mobile genetic elements. The genome of this non-pathogenic
      Clavibacter strain contained also a high number of transporters and regulatory
      genes. CONCLUSIONS: The genome sequence of the non-pathogenic Clavibacter strain
      LMG 26808 and the comparative analyses with other pathogenic Clavibacter strains
      provided a better understanding of the genetic bases of virulence and adaptation
      mechanisms present in the genus Clavibacter.

PMID- 24885541
TI  - Relationships in oocyte recipient couples - a Swedish national prospective follow
      up study.
AB  - BACKGROUND: The long-term effect of treatment with donated oocytes on women's and
      men's perception of their relationship has been little studied. Thus the aim of
      this study was to analyse satisfaction with relationships in couples at the time
      of acceptance for treatment and 2-5 years after treatment with donated gametes
      and to compare them with IVF couples treated with their own gametes. METHOD: A
      prospective follow-up study in which data were collected twice on two groups;
      cohabitating couples receiving oocyte donation and cohabitating IVF couples using
      their own gametes. A standardised instrument, the ENRICH inventory, was used to
      gain information about the couples' subjective experience of their relationships.
      RESULTS: At acceptance for treatment the couples in the two groups assessed their
      relationships as being very solid on all dimensions and that the women receiving
      treatment with oocyte showed a higher satisfaction compared to women treated with
      own gametes. For couples that did have a child, the group of women who had been
      through the oocyte donating program reported a better quality of their
      relationship than women in the control group. There were no significant
      differences in perceived relationship quality between men in the different
      groups, whether they had a child or not. CONCLUSIONS: From a long-term
      perspective couples using oocyte donation treatment have a balanced and solid
      view of their relationship and treatment, having children or not after treatment
      did not affect the nature of the relationships.

PMID- 24885542
TI  - A pragmatic, randomized, controlled study evaluating the impact of access to
      smoking cessation pharmacotherapy coverage on the proportion of successful
      quitters in a Canadian population of smokers motivated to quit (ACCESSATION).
AB  - BACKGROUND: Many smokers find the cost of smoking cessation medications a
      barrier. Financial coverage for these medications increases utilization of
      pharmacotherapies. This study assesses whether financial coverage increases the
      proportion of successful quitters. METHODS: A pragmatic, open-label, randomized,
      controlled trial was conducted in 58 Canadian sites between March 2009 and
      September 2010. Smokers (>=10 cigarettes/day) without insurance coverage who were
      motivated to quit within 14 days were randomized (1:1) in a blinded manner to
      receive either full coverage eligibility for 26 weeks or no coverage.
      Pharmacotherapies covered were varenicline, bupropion, or nicotine patches/gum.
      Investigators/subjects were unblinded to study group assignment after
      randomization and prior to choosing a smoking cessation method(s). All subjects
      received brief smoking cessation counseling. The primary outcome measure was self
      reported 7-day point prevalence of abstinence (PPA) at week 26. RESULTS: Of the
      1380 randomized subjects (coverage, 696; no coverage, 684), 682 (98.0%) and 435
      (63.6%), respectively, were dispensed at least one smoking cessation medication
      dose. The 7-day PPA at week 26 was higher in the full coverage versus no coverage
      group: 20.8% (n = 145) and 13.9% (n = 95), respectively; odds ratio (OR) = 1.64,
      95% confidence interval (CI) 1.23-2.18; p = 0.001. Urine cotinine-confirmed 7-day
      PPA at week 26 was 15.7% (n = 109) and 10.1% (n = 69), respectively; OR = 1.68,
      95% CI 1.21-2.33; p = 0.002. After pharmacotherapy, coverage eligibility was
      withdrawn from the full coverage group, continuous abstinence between weeks 26
      and 52 was 6.6% (n = 46) and 5.6% (n = 38), in the full coverage and no coverage
      groups, respectively; OR = 1.19, 95% CI 0.76-1.87; p = 0.439. CONCLUSIONS: In
      this study, the adoption of a smoking cessation medication coverage drug policy
      was an effective intervention to improve 26-week quit rates in Canada. The
      advantages were lost once coverage was discontinued. Further study is required on
      the duration of coverage to prevent relapse to smoking. (clinicaltrials.gov
      identifier: NCT00818207; the study was sponsored by Pfizer Inc.).

PMID- 24885543
TI  - Mapping dynamic QTL for plant height in triticale.
AB  - BACKGROUND: Plant height is a prime example of a dynamic trait that changes
      constantly throughout adult development. In this study we utilised a large
      triticale mapping population, comprising 647 doubled haploid lines derived from 4
      families, to phenotype for plant height by a precision phenotyping platform at
      multiple time points. RESULTS: Using multiple-line cross QTL mapping we
      identified main effect and epistatic QTL for plant height for each of the time
      points. Interestingly, some QTL were detected at all time points whereas others
      were specific to particular developmental stages. Furthermore, the contribution
      of the QTL to the genotypic variance of plant height also varied with time as
      exemplified by a major QTL identified on chromosome 6A. CONCLUSIONS: Taken
      together, our results in the small grain cereal triticale reveal the importance
      of considering temporal genetic patterns in the regulation of complex traits such
      as plant height.

PMID- 24885544
TI  - Impact of a program to prevent incivility towards and assault of healthcare staff
      in an ophtalmological emergency unit: study protocol for the PREVURGO On/Off
      trial.
AB  - BACKGROUND: The emergency department has been identified as an area within the
      health care sector with the highest reports of violence. The best way to control
      violence is to prevent it before it becomes an issue. Ideally, to prevent violent
      episodes we should eliminate all triggers of frustration and violence. Our study
      aims to assess the impact of a quality improvement multi-faceted program aiming
      at preventing incivility and violence against healthcare professionals working at
      the ophthalmological emergency department of a teaching hospital. METHODS/DESIGN:
      This study is a single-center prospective, controlled time-series study with an
      alternate-month design. The prevention program is based on the successive
      implementation of five complementary interventions: a) an organizational approach
      with a standardized triage algorithm and patient waiting number screen, b) an
      environmental approach with clear signage of the premises, c) an educational
      approach with informational videos for patients and accompanying persons in
      waiting rooms, d) a human approach with a mediator in waiting rooms and e) a
      security approach with surveillance cameras linked to the hospital security. The
      primary outcome is the rate of incivility or violence by patients, or those
      accompanying them against healthcare staff. All patients admitted to the
      ophthalmological emergency department, and those accompanying them, will be
      enrolled. In all, 45,260 patients will be included in over a 24-month period. The
      unit analysis will be the patient admitted to the emergency department. Data
      analysis will be blinded to allocation, but due to the nature of the
      intervention, physicians and patients will not be blinded. DISCUSSION: The
      strengths of this study include the active solicitation of event reporting, that
      this is a prospective study and that the study enables assessment of each of the
      interventions that make up the program. The challenge lies in identifying
      effective interventions, adapting them to the context of care in an emergency
      department, and thoroughly assessing their efficacy with a high level of
      proof.The study has been registered as a cRCT at clinicaltrials.gov (identifier:
      NCT02015884).

PMID- 24885545
TI  - A comparison of thoracic or lumbar patient-controlled epidural analgesia methods
      after thoracic surgery.
AB  - BACKGROUND: We aimed to compare patient-controlled thoracic or lumbar epidural
      analgesia methods after thoracotomy operations. METHODS: One hundred and twenty
      patients were prospectively randomized to receive either thoracic epidural
      analgesia (TEA group) or lumbar epidural analgesia (LEA group). In both groups,
      epidural catheters were administered. Hemodynamic measurements, visual analog
      scale scores at rest (VAS-R) and after coughing (VAS-C), analgesic consumption,
      and side effects were compared at 0, 2, 4, 8, 16, and 24 hours postoperatively.
      RESULTS: The VAS-R and VAS-C values were lower in the TEA group in comparison to
      the LEA group at 2, 4, 8, and 16 hours after surgery (for VAS-R, P = 0.001, P =
      0.01, P = 0.008, and P = 0.029, respectively; and for VAS-C, P = 0.035, P =
      0.023, P = 0.002, and P = 0.037, respectively). Total 24-hour analgesic
      consumption was different between groups (175 +/- 20 mL versus 185 +/- 31 mL; P =
      0.034). The comparison of postoperative complications revealed that the incidence
      of hypotension (21/57, 36.8% versus 8/63, 12.7%; P = 0.002), bradycardia (9/57,
      15.8% versus 2/63, 3.2%; P = 0.017), atelectasis (1/57, 1.8% versus 7/63, 11.1%;
      P = 0.04), and the need for intensive care unit (ICU) treatment (0/57, 0% versus
      5/63, 7.9%; P = 0.03) were lower in the TEA group in comparison to the LEA group.
      CONCLUSIONS: TEA has beneficial hemostatic effects in comparison to LEA after
      thoracotomies along with more satisfactory pain relief profile.

PMID- 24885546
TI  - Oncolytic therapy of a recombinant Newcastle disease virus D90 strain for lung
      cancer.
AB  - BACKGROUND: Lung cancer is one of the leading causes of deaths from cancer
      worldwide. Tumor virotherapy using naturally oncolytic Newcastle disease virus
      (NDV) has been shown to be safe and effective in preclinical studies and clinical
      trials. Previously, we have reported the NDV D90 strain that was isolated from
      natural source has an antiproliferative effect in human lung cancer cell line
      A549. METHODS AND RESULTS: In this study, we constructed a reverse genetics
      system based on the oncolytic NDV D90 strain and generated a recombinant NDV
      carrying a gene encoding enhanced green fluorescent protein (rNDV-GFP). The
      rescued virus rNDV-D90 and rNDV-GFP showed the similar characteristics of
      replication and apoptotic ability in lung cancer A549 cells, which suggested that
      the recombinant viruses sustained the property of tumor-selective replication and
      induced apoptosis of tumor cells. The athymic mice bearing implanted lung cancer
      were treated with the parental D90 virus, the rescued rNDV-D90 and rNDV-GFP via
      intratumoral injections, respectively. The results showed that the recombinant
      viruses as well as the parental D90 virus significantly suppressed the loss of
      body weight and tumor growth. CONCLUSIONS: The study provides a new platform to
      develop effective therapeutic agents for tumor treatment. The availability of the
      reverse genetics system for NDV D90 strain will make it possible to develop novel
      recombinant oncolytic viruses based on the NDV D90 strain for improving the
      efficacy of tumor treatment.

PMID- 24885547
TI  - Starvation of low-density lipoprotein-derived cholesterol induces bradyzoite
      conversion in Toxoplasma gondii.
AB  - BACKGROUND: Lacking enzymes for sterol synthesis, the intracellular protozoan
      Toxoplasma gondii scavenges cholesterol from host cells to multiply. T. gondii
      has a complex life cycle consisting of two asexual stages; the proliferative
      stage (tachyzoite), and the latent stage characterized by tissue cysts
      (bradyzoite). In vitro, bradyzoite development can be induced by mimicking host
      immune response stressors through treatment with IFN-gamma, heat shock, nitric
      oxide, and high pH. However, the extent to which host nutrients contribute to
      stage conversion in T. gondii is unknown. In this study, we examined the impact
      of host cholesterol levels on stage conversion in this parasite. METHODS: Growth
      of T. gondii tachyzoites (ME49 strain) was investigated in Chinese hamster ovary
      (CHO) cells using various concentrations of low-density lipoprotein (LDL), oleic
      acid, or glucose. Squalestatin, which is an inhibitor of squalene synthase and
      is, therefore, an inhibitor of sterol synthesis, was used to treat the CHO cells.
      Tachyzoite to bradyzoite conversion rates were analyzed by indirect fluorescent
      antibody tests. RESULTS: Parasite growth was significantly enhanced by addition
      of exogenous LDL, whereas no such enhancement occurred with oleic acids or
      glucose. In ME49, growth inhibition from squalestatin treatment was not obvious.
      Although growth of the RH strain was unaffected by squalestatin in the presence
      of lipoprotein, in its absence growth of this strain was suppressed. The
      frequency of BAG1-positive vacuoles in ME49 increased under lipoprotein-free
      conditions. However, addition of exogenous LDL did not increase tachyzoite to
      bradyzoite conversion in this strain. Furthermore, treatment with squalestatin
      did not enhance stage conversion. CONCLUSION: Our results suggest that LDL
      derived cholesterol levels play a crucial role in bradyzoite conversion in T.
      gondii.

PMID- 24885548
TI  - Detailed statistical analysis plan for the difficult airway management
      (DIFFICAIR) trial.
AB  - BACKGROUND: Preoperative airway assessment in Denmark is based on a non-specific
      clinical assessment left to the discretion of the responsible anesthesiologist.
      The DIFFICAIR trial compares the effect of using a systematic and consistent
      airway assessment versus a non-specific clinical assessment on the frequency of
      unanticipated difficult airway management.To prevent outcome bias and selective
      reporting, we hereby present a detailed statistical analysis plan as an amendment
      (update) to the previously published protocol for the DIFFICAIR trial.
      METHOD/DESIGN: The DIFFICAIR trial is a stratified, parallel group, cluster
      (cluster = department) randomized multicenter trial involving 28 departments of
      anesthesia in Denmark randomized to airway assessment either by the Simplified
      Airway Risk Index (SARI) or by a usual non-specific assessment. Data from
      patients' preoperative airway assessment are registered in the Danish Anesthesia
      Database. An objective score for intubation grading the severity, that is the
      severity of the intubations, as well as the frequency of unanticipated difficult
      intubation, is measured for each group.Primary outcome measures are the fraction
      of unanticipated difficult and easy intubations.The database is programmed so
      that the registration of the SARI is mandatory for the intervention group but
      invisible to controls.Data recruitment was commenced in October 2012 and ended in
      ultimo December 2013. CONCLUSION: We intend to increase the transparency of the
      data analyses regarding the DIFFICAIR trial by an a priori publication of a
      statistical analysis plan. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01718561.

PMID- 24885549
TI  - Spinal pain in adolescents: prevalence, incidence, and course: a school-based two
      year prospective cohort study in 1,300 Danes aged 11-13.
AB  - BACKGROUND: The severity and course of spinal pain is poorly understood in
      adolescents. The study aimed to determine the prevalence and two-year incidence,
      as well as the course, frequency, and intensity of pain in the neck, mid back,
      and low back (spinal pain). METHODS: This study was a school-based prospective
      cohort study. All 5th and 6th grade students (11-13 years) at 14 schools in the
      Region of Southern Denmark were invited to participate (N=1,348). Data were
      collected in 2010 and again two years later, using an e-survey completed during
      school time. RESULTS: The lifetime prevalence of spinal pain was 86% and 89% at
      baseline and follow-up, respectively. A group of 13.6% (95% CI: 11.8, 15.6) at
      baseline and 19.5% (95% CI: 17.1, 22.0) at follow-up reported that they had pain
      frequently. The frequency of pain was strongly associated with the intensity of
      pain, i.e., the majority of the participants reported their pain as relatively
      infrequent and of low intensity, whereas the participants with frequent pain also
      experienced pain of higher intensity. The two-year incidence of spinal pain
      varied between 40% and 60% across the physical locations. Progression of pain
      from one to more locations and from infrequent to more frequent was common over
      the two-year period. CONCLUSIONS: Spinal pain is common at the age of 11-15
      years, but some have more pain than others. The pain is likely to progress, i.e.,
      to more locations, higher frequency, and higher pain intensity over a two-year
      period.

PMID- 24885550
TI  - Genome-wide expression profile of the response to spinal cord injury in Xenopus
      laevis reveals extensive differences between regenerative and non-regenerative
      stages.
AB  - BACKGROUND: Xenopus laevis has regenerative and non-regenerative stages. As a
      tadpole, it is fully capable of functional recovery after a spinal cord injury,
      while its juvenile form (froglet) loses this capability during metamorphosis. We
      envision that comparative studies between regenerative and non-regenerative
      stages in Xenopus could aid in understanding why spinal cord regeneration fails
      in human beings. RESULTS: To identify the mechanisms that allow the tadpole to
      regenerate and inhibit regeneration in the froglet, we obtained a transcriptome
      wide profile of the response to spinal cord injury in Xenopus regenerative and
      non-regenerative stages. We found extensive transcriptome changes in regenerative
      tadpoles at 1 day after injury, while this was only observed by 6 days after
      injury in non-regenerative froglets. In addition, when comparing both stages, we
      found that they deployed a very different repertoire of transcripts, with more
      than 80% of them regulated in only one stage, including previously unannotated
      transcripts. This was supported by gene ontology enrichment analysis and
      validated by RT-qPCR, which showed that transcripts involved in metabolism,
      response to stress, cell cycle, development, immune response and inflammation,
      neurogenesis, and axonal regeneration were regulated differentially between
      regenerative and non-regenerative stages. CONCLUSIONS: We identified differences
      in the timing of the transcriptional response and in the inventory of regulated
      transcripts and biological processes activated in response to spinal cord injury
      when comparing regenerative and non-regenerative stages. These genes and
      biological processes provide an entry point to understand why regeneration fails
      in mammals. Furthermore, our results introduce Xenopus laevis as a genetic model
      organism to study spinal cord regeneration.

PMID- 24885551
TI  - Efficacy and cost-effectiveness of an experimental short-term inpatient
      Dialectical Behavior Therapy (DBT) program: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Borderline Personality Disorder (BPD) is a serious psychiatric
      condition associated with substantial mortality, burden and public health costs.
      DBT is the treatment model with the largest number of published research articles
      showing effectiveness. However, some patients are not sufficiently engaged in
      outpatient treatment while presenting severe parasuicidal behavior, making
      hospitalization necessary. The Center for Personality Disorders Jelgersma
      developed an intensive 12-week inpatient DBT program that (i) rapidly reduces
      core borderline symptoms like suicidal behavior, (ii) minimizes the negative
      effects of an inpatient setting, and (iii) enhances compliance with outpatient
      treatment. We evaluate the (cost-) effectiveness of this experimental program.
      METHODS/DESIGN: Seventy patients, aged 18 to 45 years with a primary diagnosis of
      BPD, showing a chronic pattern of parasuicidal gestures and/or reporting high
      degrees of severity of other borderline symptoms, are randomly allocated to the
      control and intervention groups. Subjects in the control group receive standard
      outpatient DBT, provided in one of three regular mental health settings in GGZ
      Rivierduinen. Subjects in the intervention group receive 12 weeks of intensified
      inpatient DBT plus six months of standard DBT, provided in the Center for
      Personality Disorders Jelgersma. The primary outcome is the number of suicide
      attempts/self-harming acts. Secondary outcomes are severity of other borderline
      complaints, quality of life, general psychopathological symptoms and health care
      utilization and productivity costs. Data are gathered using a prospective, two
      (group: intervention and control) by five (time of measurement) repeated measures
      factorial design.Participants will complete three-monthly outcome assessments in
      the course of therapy: at baseline, and 12, 24, 36 and 52 weeks after the start
      of the treatment. The period of recruitment started in March 2012 and the study
      will end in December 2014. DISCUSSION: Highly suicidal outpatient patients can
      pose a dilemma for mental health care professionals. Although hospitalization
      seems inevitable under some circumstances, it has proven to be harmful in its own
      right. This paper outlines the background and methods of a randomized trial
      evaluating the possible surplus value of a short-term inpatient DBT program.

PMID- 24885552
TI  - Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an
      indicator of prostate cancer aggressiveness.
AB  - BACKGROUND: We tested the feasibility of a simple method for assessment of
      prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance
      imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between
      prostate cancer and healthy prostatic tissue. METHODS: The requirement for
      institutional review board approval was waived. A set of 20 standardized core
      transperineal saturation biopsy specimens served as the reference standard for
      placement of regions of interest on ADC maps in tumorous and normal prostatic
      tissue of 22 men with PCa (median Gleason score: 7; range, 6-9). A total of 128
      positive sectors were included for evaluation. Two diagnostic ratios were
      computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the
      ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC
      central ratio (the ratio between tumor ADC and normal central zone tissue, ADC
      CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason
      8 and 9) was assessed using the area under the receiver operating characteristic
      curve (AUC). RESULTS: Both ADC ratios presented significantly lower values in
      high-risk tumors (0.48 +/- 0.13 for ADC-CR and 0.40 +/- 0.09 for ADC-PR) compared
      with low-risk tumors (0.66 +/- 0.17 for ADC-CR and 0.54 +/- 0.09 for ADC-PR) (p <
      0.001) and had better diagnostic performance (ADC-CR AUC = 0.77, sensitivity =
      82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%,
      specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%,
      specificity = 70.6%) for identifying high-risk lesions. CONCLUSIONS: The ADC
      ratio as an intrapatient-normalized diagnostic tool may be better in detecting
      high-grade lesions compared with analysis based on tumor ADCs alone, and may
      reduce the rate of biopsies.

PMID- 24885553
TI  - Towards a common terminology: a simplified framework of interventions to promote
      and integrate evidence into health practices, systems, and policies.
AB  - BACKGROUND: A wide range of diverse and inconsistent terminology exists in the
      field of knowledge translation. This limits the conduct of evidence syntheses,
      impedes communication and collaboration, and undermines knowledge translation of
      research findings in diverse settings. Improving uniformity of terminology could
      help address these challenges. In 2012, we convened an international working
      group to explore the idea of developing a common terminology and an overarching
      framework for knowledge translation interventions. FINDINGS: Methods included
      identifying and summarizing existing frameworks, mapping together a subset of
      those frameworks, and convening a multi-disciplinary group to begin working
      toward consensus. The group considered four potential approaches to creating a
      simplified framework: melding existing taxonomies, creating a framework of
      intervention mechanisms rather than intervention strategies, using a consensus
      process to expand one of the existing models/frameworks used by the group, or
      developing a new consensus framework. CONCLUSIONS: The work group elected to
      draft a new, simplified consensus framework of interventions to promote and
      integrate evidence into health practices, systems and policies. The framework
      will include four key components: strategies and techniques (active ingredients),
      how they function (causal mechanisms), how they are delivered (mode of delivery),
      and what they aim to change (intended targets). The draft framework needs to be
      further developed by feedback and consultation with the research community and
      tested for usefulness through application and evaluation.

PMID- 24885554
TI  - Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous
      cell carcinoma.
AB  - BACKGROUND: Standard therapy for patients with stage I-III squamous cell
      carcinoma (SCC) of the anal canal is chemo-radiotherapy with 5-fluorouracil (5
      FU) and mitomycin C (MMC). While there is limited published evidence to
      substitute capecitabine (CAP) for 5-FU, the objectives of the study were to
      describe the toxicity, dose intensity and outcomes of a sequential cohort of
      patients treated with chemo-radiotherapy with CAP and MCC in a population-based
      setting. METHODS: Patients with stage I-III malignancies of the anal canal
      referred between February 2010 and March 2012 were included. Dose intensity was
      calculated by comparing delivered versus planned radiation and chemotherapy
      treatments and toxicity was retrospectively graded according to standard protocol
      specified criteria. RESULTS: Among 66 eligible patients, median planned dose of
      radiation was 51.9 Gy over 5.5 weeks, range 25.0 to 63 Gy, and dose intensity was
      98%. Median delivered dose of MCC delivered was 12 mg/m2 on day one, week one
      while median CAP dose was 825 mg/m2 twice daily on radiation days. CAP dose
      reductions due to toxicity were recorded for 13 patients (20%). Median follow-up
      was 20 months and 94% of patients with squamous cell histology had no evidence of
      relapse. CONCLUSIONS: Chemo-radiation with CAP plus MMC is well tolerated and may
      be a reasonable consideration for patients with stage I-III SCC of the anal
      canal. A range of planned radiation dose was observed and longer follow-up is
      necessary to ensure that patients who received lower doses of radiation have
      similar outcomes to those who received larger doses.

PMID- 24885556
TI  - Immunotoxicity of silver nanoparticles in an intravenous 28-day repeated-dose
      toxicity study in rats.
AB  - BACKGROUND: Nanosilver is used in a variety of medical and consumer products
      because of its antibacterial activity. This wide application results in an
      increased human exposure. Knowledge on the systemic toxicity of nanosilver is,
      however, relatively scarce. In a previous study, the systemic toxicity of 20 nm
      silver nanoparticles (Ag-NP) was studied in a 28-day repeated-dose toxicity study
      in rats. Ag-NP were intravenously administered with a maximum dose of 6 mg/kg
      body weight (bw)/day. Several immune parameters were affected: reduced thymus
      weight, increased spleen weight and spleen cell number, a strongly reduced NK
      cell activity, and reduced IFN-gamma production were observed. METHODS: Prompted
      by these affected immune parameters, we wished to assess exposure effects on the
      functional immune system. Therefore, in the present study the T-cell dependent
      antibody response (TDAR) to keyhole limpet hemocyanin (KLH) was measured in a
      similar 28-day intravenous repeated-dose toxicity study. In addition, a range of
      immunological parameters was measured. Data obtained using the benchmark dose
      (BMD) approach were analyzed by fitting dose-response models to the parameters
      measured. RESULTS: A reduction in KLH-specific IgG was seen, with a lowest 5%
      lower confidence bound of the BMD (BMDL) of 0.40 mg/kg bw/day. This suggests that
      Ag-NP induce suppression of the functional immune system. Other parameters
      sensitive to Ag-NP exposure were in line with our previous study: a reduced
      thymus weight with a BMDL of 0.76 mg/kg bw/day, and an increased spleen weight,
      spleen cell number, and spleen cell subsets, with BMDLs between 0.36 and 1.11
      mg/kg bw/day. Because the effects on the spleen are not reflected by increased
      KLH-specific IgG, they, however, do not suggest immune stimulation. CONCLUSIONS:
      Intravenous Ag-NP administration in a 28-day repeated-dose toxicity study induces
      suppression of the functional immune system. This finding underscores the
      importance to study the TDAR to evaluate immunotoxicity and not to rely solely on
      measuring immune cell subsets.

PMID- 24885557
TI  - The validity and reliability of the self-directed learning instrument (SDLI) in
      mainland Chinese nursing students.
AB  - BACKGROUND: Self-directed learning is crucial to the professional development of
      nursing students, and which enables them to expand the knowledge and enhance the
      quality of their practice. A validated self-directed learning instrument is
      important not only in assessing the individual's self-directed learning level,
      but also in evaluating the effectiveness of teaching or learning methods. The aim
      of this study is to evaluate the validity and reliability of the SDLI in mainland
      Chinese nursing students. METHODS: A cross-sectional design with convenience
      sampling was used to recruit participants from three nursing schools. The
      mainland Chinese version of SDLI was tested with respect to validity and
      reliability in 1,499 nursing students, and another 30 nursing students were
      invited to evaluate the test-retest reliability of the scale in 7 days interval.
      RESULTS: Explorary factor analysis identified a four-factor structure, accounting
      for 56.101% of the total variance. The confirmatory factor analysis showed a good
      overall fit of this four-factor model. Convergent validity was supported by the
      highly positive Pearson's correlation between SDLI score and SRSSDL score (r =
      .876, p = .000). Cronbach's alpha for internal consistency of overall scale was
      .916, and 4 dimensions were between .755-.825.The test-retest reliability of
      overall scale was .850, and 4 dimensions were between .708-.821. The intraclass
      correlation coefficient (ICC) of overall scale was .916, and 4 dimensions were
      .822-.889. CONCLUSIONS: This study indicates that the SDLI is a valid and
      reliable instrument for assessing self-directed learning in mainland Chinese
      nursing students. Nurse educators could use such knowledge to develop their roles
      and plan to support nursing students in becoming self-directed learners and
      lifelong learner.

PMID- 24885555
TI  - BMP2-induced chemotaxis requires PI3K p55gamma/p110alpha-dependent
      phosphatidylinositol (3,4,5)-triphosphate production and LL5beta recruitment at
      the cytocortex.
AB  - BACKGROUND: BMP-induced chemotaxis of mesenchymal progenitors is fundamental for
      vertebrate development, disease and tissue repair. BMP2 induces Smad and non-Smad
      signalling. Whereas signal transduction via Smads lead to transcriptional
      responses, non-Smad signalling induces both, transcriptional and immediate/early
      non-transcriptional responses. However, the molecular mechanisms by which BMP2
      facilitates planar cell polarity, cortical actin rearrangements, lamellipodia
      formation and chemotaxis of mesenchymal progenitors are poorly understood. Our
      aim was to uncover the molecular mechanism by which BMP2 facilitates chemotaxis
      via the BMP2-dependent activation of PI3K and spatiotemporal control of PIP3
      production important for actin rearrangements at the mesenchymal cell cytocortex.
      RESULTS: We unveiled the molecular mechanism by which BMP2 induces non-Smad
      signalling by PI3K and the role of the second messenger PIP3 in BMP2-induced
      planar cell polarity, cortical actin reorganisation and lamellipodia formation.
      By using protein interaction studies, we identified the class Ia PI3K regulatory
      subunit p55gamma to act as a specific and non-redundant binding partner for BMP
      receptor type II (BMPRII) in concert with the catalytic subunit p110alpha. We
      mapped the PI3K interaction to a region within the BMPRII kinase. Either BMP2
      stimulation or increasing amounts of BMPRI facilitated p55gamma association with
      BMPRII, but BMPRII kinase activity was not required for the interaction. We
      visualised BMP2-dependent PIP3 production via PI3K p55gamma/p110alpha and were
      able to localise PIP3 to the leading edge of intact cells during the process of
      BMP2-induced planar cell polarity and actin dependent lamellipodia formation.
      Using mass spectrometry, we found the highly PIP3-sensitive PH-domain protein
      LL5beta to act as a novel BMP2 effector in orchestrating cortical actin
      rearrangements. By use of live cell imaging we found that knock-down of p55gamma
      or LL5beta or pharmacological inhibition of PI3K impaired BMP2-induced migratory
      responses. CONCLUSIONS: Our results provide evidence for an important
      contribution of the BMP2-PI3K (p55gamma/p110alpha)- PIP3-LL5beta signalling axis
      in mesenchymal progenitor cell chemotaxis. We demonstrate molecular insights into
      BMP2-induced PI3K signalling on the level of actin reorganisation at the leading
      edge cytocortex. These findings are important to better understand BMP2-induced
      cytoskeletal reorganisation and chemotaxis of mesenchymal progenitors in
      different physiological or pathophysiological contexts.

PMID- 24885558
TI  - Osteoporosis resulting from acute lymphoblastic leukemia in a 7-year-old boy: a
      case report.
AB  - INTRODUCTION: Osteoporosis in children is rare and usually secondary to an
      underlying disease process whose diagnosis may be difficult to detect.
      Etiological factors responsible for osteoporosis secondary to chronic illness
      include immobility, pubertal delay and other hormonal disturbances. Rarely, it
      can be a manifestation of acute lymphoblastic leukemia. Most of the reported bone
      fracture incidences associated with acute lymphoblastic leukemia occur during the
      course of the chemotherapy, not at the point of the first symptoms of leukemic
      disease, as happened with the case presented here. CASE PRESENTATION: A 7-year
      old Asian Balinese boy presented with back pain. His anteroposterior pelvic
      radiograph showed osteoporotic bone. A bone age study revealed growth failure of
      his metacarpals, phalanges and sesamoid. His total bone mass density was 97% age
      match. However, a peripheral blood smear showed normochromic anemia with
      thrombocytopenia. Immunophenotyping of his peripheral blood revealed no dominant
      markers, but a bone marrow aspiration confirmed a diagnosis of acute
      lymphoblastic leukemia. CONCLUSIONS: Osteoporosis was the only manifestation of
      the child's underlying acute lymphoblastic leukemia. Leukemia was diagnosed when
      his bone marrow was found to contain more than 25% blasts. Because of leucopenia,
      the immunophenotype failed to reveal a dominant marker in this case, thus we were
      unable to classify the acute lymphoblastic leukemia.

PMID- 24885559
TI  - Too many crying babies: a systematic review of pain management practices during
      immunizations on YouTube.
AB  - BACKGROUND: Early childhood immunizations, although vital for preventative
      health, are painful and too often lead to fear of needles. Effective pain
      management strategies during infant immunizations include breastfeeding, sweet
      solutions, and upright front-to-front holding. However, it is unknown how often
      these strategies are used in clinical practice. We aimed to review the content of
      YouTube videos showing infants being immunized to ascertain parents' and health
      care professionals' use of pain management strategies, as well as to assess
      infants' pain and distress. METHODS: A systematic review of YouTube videos
      showing intramuscular injections in infants less than 12 months was completed
      using the search terms "baby injection" and "baby vaccine" to assess (1) the use
      of pain management strategies and (2) infant pain and distress. Pain was assessed
      by crying duration and pain scores using the FLACC (Face, Legs, Activity, Cry,
      Consolability) tool. RESULTS: A total of 142 videos were included and coded by
      two trained individual viewers. Most infants received one injection (range of one
      to six). Almost all (94%) infants cried before or during the injections for a
      median of 33 seconds (IQR = 39), up to 146 seconds. FLACC scores during the
      immunizations were high, with a median of 10 (IQR = 3). No videos showed
      breastfeeding or the use of sucrose/sweet solutions during the injection(s), and
      only four (3%) videos showed the infants being held in a front-to-front position
      during the injections. Distraction using talking or singing was the most commonly
      used (66%) pain management strategy. CONCLUSIONS: YouTube videos of infants being
      immunized showed that infants were highly distressed during the procedures. There
      was no use of breastfeeding or sweet solutions and limited use of upright or
      front-to-front holding during the injections. This systematic review will be used
      as a baseline to evaluate the impact of future knowledge translation
      interventions using YouTube to improve pain management practices for infant
      immunizations.

PMID- 24885560
TI  - Single and combinatorial chromatin coupling events underlies the function of
      transcript factor Kruppel-like factor 11 in the regulation of gene networks.
AB  - BACKGROUND: Kruppel-like factors (KLFs) are a group of master regulators of gene
      expression conserved from flies to human. However, scant information is available
      on either the mechanisms or functional impact of the coupling of KLF proteins to
      chromatin remodeling machines, a deterministic step in transcriptional
      regulation. RESULTS AND DISCUSSION: In the current study, we use genome-wide
      analyses of chromatin immunoprecipitation (ChIP-on-Chip) and Affymetrix-based
      expression profiling to gain insight into how KLF11, a human transcription factor
      involved in tumor suppression and metabolic diseases, works by coupling to three
      co-factor groups: the Sin3-histone deacetylase system, WD40-domain containing
      proteins, and the HP1-histone methyltransferase system. Our results reveal that
      KLF11 regulates distinct gene networks involved in metabolism and growth by using
      single or combinatorial coupling events. CONCLUSION: This study, the first of its
      type for any KLF protein, reveals that interactions with multiple chromatin
      systems are required for the full gene regulatory function of these proteins.

PMID- 24885561
TI  - Quality of reporting on randomized controlled trials of acupuncture for stroke
      rehabilitation.
AB  - BACKGROUND: Results from clinical studies on acupuncture for stroke
      rehabilitation are contradictory. The reason for the inconsistent findings
      especially lie in the transparency and accuracy of randomized controlled trials
      (RCTs) reports. This study aims to analyze the quality of reporting and its
      correlates in RCTs on acupuncture for stroke rehabilitation. METHODS: Quality of
      reporting for included papers was assessed against a subset of criteria adapted
      from the CONSORT 2010 statement and STRICTA. An overall quality score (OQS) and a
      combined key methodological index score (MIS) was calculated for each trial.
      Then, factors associated with OQS and MIS were identified. RESULTS: A total of 15
      RCTs were included in full text. The median OQS based on the CONSORT statement
      and STRICTA was 8 and 12, respectively. The significant predictors for CONSORT
      OQS was funding source, for STRICTA was year of publication. With regard to the
      MIS, no variable was associated with improved methodological quality.
      CONCLUSIONS: Our study found that the overall quality of reporting on RCTs of
      acupuncture for stroke rehabilitation was general or good. But some items'
      reporting was found where information was insufficient or inadequate in most
      studies which needed substantial improvement.

PMID- 24885562
TI  - Acceptance of illness and satisfaction with life among malaria patients in rivers
      state, Nigeria.
AB  - BACKGROUND: Health condition is one of the basic factors affecting satisfaction
      with life, and the level of illness acceptance. The purpose of the study was to
      analyse the level of illness acceptance, the level of satisfaction with life
      among malaria patients, and the level of trust placed in the physician and the
      nurse. METHODS: The study employs the method of diagnostic survey based on
      standardised AIS and SWLS scales, as well as Anderson and Dedrick's PPTS and PNTS
      scales. RESULTS: The average AIS level was 12 points, while the average level of
      SwL at the SWLS scale was 16.5 points. The average level of trust in the
      physician and the nurse amounted to 50.6 points and 51.4 points, respectively.
      The correlation between the level of illness acceptance and self-evaluated
      satisfaction with life was statistically significant, with R = 0.56. The marital
      status influenced the level of illness acceptance with p < 0.05 and the level of
      satisfaction with life with p < 0.05. The employment status affected the level of
      satisfaction with life with p < 0.05 and the level of illness acceptance with p <
      0.05. CONCLUSIONS: The majority of malaria patients did not accept their illness,
      while the level of satisfaction with life was low. The majority of respondents
      trusted their physician and nurse. There is a statistically significant
      correlation between the level of illness acceptance and the self-evaluated
      satisfaction with life. The marital status had a statistically significant effect
      on the acceptance of illness and the satisfaction with life. The individuals who
      had a job demonstrated higher levels of quality of life and illness acceptance.

PMID- 24885564
TI  - Identification of novel driver mutations of the discoidin domain receptor 2
      (DDR2) gene in squamous cell lung cancer of Chinese patients.
AB  - BACKGROUND: Although many of the recently approved genomically targeted therapies
      have improved outcomes for patients in non-small-cell lung cancer (NSCLC) with
      lung adenocarcinoma, little is known about the genomic alterations that drive
      lung squamous cell cancer (SCC) and development of effective targeted therapies
      in lung SCC is a promising area to be further investigated. Discoidin domain
      receptor 2 (DDR2), is a novel receptor tyrosine kinases that respond to several
      collagens and involved in tissue repair, primary and metastatic cancer
      progression. METHODS: Expression of DDR2 mRNA was analyzed in 54 lung SCC tissues
      by qRT-PCR. Over-expression approaches were used to investigate the biological
      functions of DDR2 and its' mutations in lung SCC cells. Conventional Sanger
      sequencing was used to investigate the mutations of DDR2 gene in 86 samples. The
      effect of DDR2 and its' mutations on proliferation was evaluated by MTT and
      colony formation assays; cell migration and invasion was evaluated by trasnwell
      assays. Lung SCC cells stably transfected with pEGFP-DDR2 WT, pEGFP-DDR2-S131C or
      empty vector were injection into nude mice to study the effect of DDR2 and its'
      mutation on tumorigenesis in vivo. Protein and mRNA expression levels of E
      cadherin and MMP2 were determined by qRT-PCR and western blot analysis.
      Differences between groups were tested for significance using Student's t-test
      (two-tailed). RESULTS: In this study, we found that DDR2 mRNA levels were
      significantly decreased in 54 lung SCC tissues compared with normal lung tissues.
      Moreover, there were 3 novel DDR2 mutations (G531V, S131C, T681I) in 4 patients
      and provide the mutation rate of 4.6% in the 86 patients with lung SCC. The
      mutation of S131C in DDR2 could promote lung SCC cells proliferation, migration
      and invasion via inducing MMP-2, but reducing E-cadherin expression. CONCLUSIONS:
      These data indicated that the novel DDR2 mutation may contribute to the
      development and progression of lung SCC and this effect may be associated with
      increased proliferation and invasiveness, at least in part, via regulating E
      cadherin expression.

PMID- 24885565
TI  - Time to address gender discrimination and inequality in the health workforce.
AB  - Gender is a key factor operating in the health workforce. Recent research
      evidence points to systemic gender discrimination and inequalities in health pre
      service and in-service education and employment systems. Human resources for
      health (HRH) leaders' and researchers' lack of concerted attention to these
      inequalities is striking, given the recognition of other forms of discrimination
      in international labour rights and employment law discourse. If not acted upon,
      gender discrimination and inequalities result in systems inefficiencies that
      impede the development of the robust workforces needed to respond to today's
      critical health care needs.This commentary makes the case that there is a clear
      need for sex- and age-disaggregated and qualitative data to more precisely
      illuminate gender-related trends and dynamics in the health workforce. Because of
      their importance for measurement, the paper also presents definitions and
      examples of sex or gender discrimination and offers specific case examples.At a
      broader level, the commentary argues that gender equality should be an HRH
      research, leadership, and governance priority, where the aim is to strengthen
      health pre-service and continuing professional education and employment systems
      to achieve better health systems outcomes, including better health coverage. Good
      HRH leadership, governance, and management involve recognizing the diversity of
      health workforces, acknowledging gender constraints and opportunities,
      eliminating gender discrimination and equalizing opportunity, making health
      systems responsive to life course events, and protecting health workers' labour
      rights at all levels. A number of global, national and institution-level actions
      are proposed to move the gender equality and HRH agendas forward. 

PMID- 24885563
TI  - Nucleomorph and plastid genome sequences of the chlorarachniophyte Lotharella
      oceanica: convergent reductive evolution and frequent recombination in
      nucleomorph-bearing algae.
AB  - BACKGROUND: Nucleomorphs are residual nuclei derived from eukaryotic
      endosymbionts in chlorarachniophyte and cryptophyte algae. The endosymbionts that
      gave rise to nucleomorphs and plastids in these two algal groups were green and
      red algae, respectively. Despite their independent origin, the chlorarachniophyte
      and cryptophyte nucleomorph genomes share similar genomic features such as
      extreme size reduction and a three-chromosome architecture. This suggests that
      similar reductive evolutionary forces have acted to shape the nucleomorph genomes
      in the two groups. Thus far, however, only a single chlorarachniophyte
      nucleomorph and plastid genome has been sequenced, making broad evolutionary
      inferences within the chlorarachniophytes and between chlorarachniophytes and
      cryptophytes difficult. We have sequenced the nucleomorph and plastid genomes of
      the chlorarachniophyte Lotharella oceanica in order to gain insight into
      nucleomorph and plastid genome diversity and evolution. RESULTS: The L. oceanica
      nucleomorph genome was found to consist of three linear chromosomes totaling ~610
      kilobase pairs (kbp), much larger than the 373 kbp nucleomorph genome of the
      model chlorarachniophyte Bigelowiella natans. The L. oceanica plastid genome is
      71 kbp in size, similar to that of B. natans. Unexpectedly long (~35 kbp) sub
      telomeric repeat regions were identified in the L. oceanica nucleomorph genome;
      internal multi-copy regions were also detected. Gene content analyses revealed
      that nucleomorph house-keeping genes and spliceosomal intron positions are well
      conserved between the L. oceanica and B. natans nucleomorph genomes. More
      broadly, gene retention patterns were found to be similar between nucleomorph
      genomes in chlorarachniophytes and cryptophytes. Chlorarachniophyte plastid
      genomes showed near identical protein coding gene complements as well as a high
      level of synteny. CONCLUSIONS: We have provided insight into the process of
      nucleomorph genome evolution by elucidating the fine-scale dynamics of sub
      telomeric repeat regions. Homologous recombination at the chromosome ends appears
      to be frequent, serving to expand and contract nucleomorph genome size. The main
      factor influencing nucleomorph genome size variation between different
      chlorarachniophyte species appears to be expansion-contraction of these telomere
      associated repeats rather than changes in the number of unique protein coding
      genes. The dynamic nature of chlorarachniophyte nucleomorph genomes lies in stark
      contrast to their plastid genomes, which appear to be highly stable in terms of
      gene content and synteny.

PMID- 24885566
TI  - Open reduction and closed reduction internal fixation in treatment of femoral
      neck fractures: a meta-analysis.
AB  - BACKGROUND: A meta-analysis was performed to assess the association between
      healing rate, avascular necrosis (AVN) of femoral head and two reductions-open
      reduction internal fixation (ORIF) and closed reduction internal fixation (CRIF)
      for femoral neck fracture. METHODS: A literature-based search was conducted to
      identify all relevant studies published before September 10, 2013. The odd ratio
      (OR) and 95% confidence interval (CI) were used for estimating the effects of the
      two reduction methods. Data were independently extracted by two investigators who
      reached a consensus on all of the items. The heterogeneity between studies was
      examined by chi2-based Q statistic. Egger's regression analysis was used to
      evaluate publication bias. Statistical analysis was performed by Stata 10.0
      software. RESULTS: We examined 14 publications. The results of the present meta
      analysis showed that AVN of femoral head were significant associated with the two
      reductions (CRIF vs. ORIF, OR=1.746, 95% CI 1.159-2.628, p=0.008), while the
      healing rate were not (CRIF vs. ORIF, OR=0.853, 95% CI 0.573-1.270, p=0.433).
      CONCLUSION: The present meta-analysis indicated the risk of AVN of femoral head
      was significant higher after CRIF fixation compared with ORIF, but no association
      between the healing rate and the two reductions for femoral neck fracture.

PMID- 24885567
TI  - Maternal embryonic leucine zipper kinase enhances gastric cancer progression via
      the FAK/Paxillin pathway.
AB  - BACKGROUND: Elevated MELK expression is featured in multiple tumors and
      correlated with tumorigenesis and tumor development. This study is aimed to
      investigate the mechanisms of MELK-mediated development of gastric cancer.
      METHODS: MELK expression levels in human gastric cancer were determined by
      quantitative-PCR and immunohistochemistry. The effect of MELK on cell activity
      was explored by knockdown and overexpression experiments. Cell growth was
      measured using the CCK-8 assay. Apoptosis and cell cycle distributions were
      analyzed by flow cytometry. Migration and invasion were tested using a transwell
      migration assay. Cytoskeletal changes were analyzed by immunofluorescence. To
      explore the molecular mechanism and effect of MELK on migration and invasion,
      Western blotting was used to analyze the FAK/Paxillin pathway and pull down
      assays for the activity of small Rho GTPases. In vivo tumorigenicity and
      peritoneal metastasis experiments were performed by tumor cell engraftment into
      nude mice. RESULTS: MELK mRNA and protein expression were both elevated in human
      gastric cancer, and this was associated with chemoresistance to 5-fluorouracil (5
      FU). Knockdown of MELK significantly suppressed cell proliferation, migration and
      invasion of gastric cancer both in vitro and in vivo, decreased the percentages
      of cells in the G1/G0 phase and increased those in the G2/M and S phases.
      Moreover, knockdown of MELK decreased the amount of actin stress fibers and
      inhibited RhoA activity. Finally, knockdown of MELK decreased the phosphorylation
      of the FAK and paxillin, and prevented gastrin-stimulated FAK/paxillin
      phosphorylation. By contrast, MELK overexpression had the opposite effect.
      CONCLUSIONS: MELK promotes cell migration and invasion via the FAK/Paxillin
      pathway, and plays an important role in the occurrence and development of gastric
      cancer. MELK may be a potential target for treatment against gastric cancer.

PMID- 24885568
TI  - Integrative analysis of the transcriptome profiles observed in type 1, type 2 and
      gestational diabetes mellitus reveals the role of inflammation.
AB  - BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease, while type 2 (T2D)
      and gestational diabetes (GDM) are considered metabolic disturbances. In a
      previous study evaluating the transcript profiling of peripheral mononuclear
      blood cells obtained from T1D, T2D and GDM patients we showed that the gene
      profile of T1D patients was closer to GDM than to T2D. To understand the
      influence of demographical, clinical, laboratory, pathogenetic and treatment
      features on the diabetes transcript profiling, we performed an analysis
      integrating these features with the gene expression profiles of the annotated
      genes included in databases containing information regarding GWAS and immune cell
      expression signatures. METHODS: Samples from 56 (19 T1D, 20 T2D, and 17 GDM)
      patients were hybridized to whole genome one-color Agilent 4x44k microarrays. Non
      informative genes were filtered by partitioning, and differentially expressed
      genes were obtained by rank product analysis. Functional analyses were carried
      out using the DAVID database, and module maps were constructed using the Genomica
      tool. RESULTS: The functional analyses were able to discriminate between T1D and
      GDM patients based on genes involved in inflammation. Module maps of
      differentially expressed genes revealed that modulated genes: i) exhibited
      transcription profiles typical of macrophage and dendritic cells; ii) had been
      previously associated with diabetic complications by association and by meta
      analysis studies, and iii) were influenced by disease duration, obesity, number
      of gestations, glucose serum levels and the use of medications, such as
      metformin. CONCLUSION: This is the first module map study to show the influence
      of epidemiological, clinical, laboratory, immunopathogenic and treatment features
      on the transcription profiles of T1D, T2D and GDM patients.

PMID- 24885569
TI  - Antiviral activity and possible mode of action of ellagic acid identified in
      Lagerstroemia speciosa leaves toward human rhinoviruses.
AB  - BACKGROUND: Human rhinoviruses (HRVs) are responsible for more than half of all
      cases of the common cold and cause billions of USD annually in medical visits and
      school and work absenteeism. An assessment was made of the cytotoxic and
      antiviral activities and possible mode of action of the tannin ellagic acid from
      the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses,
      HRV-2, -3, and -4. METHODS: The antiviral property and mechanism of action of
      ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse
      transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those
      of the currently used broad-spectrum antiviral agent, ribavirin. RESULTS: As
      judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3,
      and 2.2 times more toxic toward HRV-2 (38 MUg/mL), HRV-3 (31 MUg/mL), and HRV-4
      (29 MUg/mL) than ribavirin, respectively. The inhibition rate of preincubation
      with 50 MUg/mL ellagic acid was 17%, whereas continuous presence of ellagic acid
      during infection led to a significant increase in the inhibition (70%). Treatment
      with 50 MUg/mL ellagic acid considerably suppressed HRV-4 infection only when
      added just after the virus inoculation (0 h) (87% inhibition), but not before -1
      h or after 1 h or later (<20% inhibition). These findings suggest that ellagic
      acid does not interact with the HRV-4 particles and may directly interact with
      the human cells in the early stage of HRV infections to protect the cells from
      the virus destruction. Furthermore, RT-PCR analysis revealed that 50 MUg/mL
      ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells,
      suggesting that ellagic acid inhibits virus replication by targeting on cellular
      molecules, rather than virus molecules. CONCLUSIONS: Global efforts to reduce the
      level of antibiotics justify further studies on L. speciosa leaf-derived
      materials containing ellagic acid as potential anti-HRV products or a lead
      molecule for the prevention or treatment of HRV infection.

PMID- 24885570
TI  - Incidental findings on cardiac computed tomography in incident hemodialysis
      patients: the predictors of arrhythmic and cardiovascular events in end-stage
      renal disease (PACE) study.
AB  - BACKGROUND: This is the first study that has examined non-cardiac incidental
      findings in research cardiac computed tomography (CT) of hemodialysis patients
      and their relationship with patient characteristics. METHODS: We performed a
      cross-sectional analysis in the Predictors of Arrhythmic and Cardiovascular
      Events in End-Stage Renal Disease (PACE) study, a prospective cohort study on
      incident hemodialysis patients. Non-cardiac structures in the cardiac CT scan
      were reviewed and evaluated. The type and frequencies of non-cardiac incidental
      CT findings were summarized. Univariate and multivariate logistic regression were
      performed to analyze the associations between gender, older age, obesity, history
      of cardiovascular disease (CVD), smoking status, history of chronic pulmonary
      disease and history of cancer with presence of any incidental CT findings and,
      separately, pulmonary nodules. RESULTS: Among the 260 participants, a total of
      229 non-cardiac incidental findings were observed in 145 participants (55.8% of
      all participants). Of these findings, pulmonary nodules were the most common
      incidental finding (24.2% of all findings), and 41.3% of them requiring further
      follow-up imaging per radiology recommendation. Vascular and gastrointestinal
      findings occurred in 11.8% and 15.3% of participants, respectively. Participants
      65 years or older had a higher odds of any incidental findings (Odds Ratio (OR)
      =2.55; 95% Confidence Intervals (CI) 1.30, 4.99) and pulmonary nodules (OR=4.80;
      95% CI 2.51, 9.18). Prior history of CVD was independently and significantly
      associated with any incidental findings (OR=2.00; 95% CI 1.19, 3.40); but not
      with the presence of pulmonary nodules. CONCLUSIONS: We demonstrate that the
      prevalence of incidental findings by cardiac CT scanning is extremely high among
      patients on hemodialysis. Further investigations to follow-up on the high
      occurrence of incidental findings during our research study and potentially
      clinical studies raises important practical, ethical and medico-legal issues that
      need to be carefully considered in research projects using imaging studies.

PMID- 24885571
TI  - A variant of green fluorescent protein exclusively deposited to active
      intracellular inclusion bodies.
AB  - BACKGROUND: Inclusion bodies (IBs) were generally considered to be inactive
      protein deposits and did not hold any attractive values in biotechnological
      applications. Recently, some IBs of recombinant proteins were confirmed to show
      their functional properties such as enzyme activities, fluorescence, etc. Such
      biologically active IBs are not commonly formed, but they have great potentials
      in the fields of biocatalysis, material science and nanotechnology. RESULTS: In
      this study, we characterized the IBs of DL4, a deletion variant of green
      fluorescent protein which forms active intracellular aggregates. The DL4 proteins
      expressed in Escherichia coli were exclusively deposited to IBs, and the IBs were
      estimated to be mostly composed of active proteins. The spectral properties and
      quantum yield of the DL4 variant in the active IBs were almost same with those of
      its native protein. Refolding and stability studies revealed that the deletion
      mutation in DL4 didn't affect the folding efficiency of the protein, but
      destabilized its structure. Analyses specific for amyloid-like structures
      informed that the inner architecture of DL4 IBs might be amorphous rather than
      well-organized. The diameter of fluorescent DL4 IBs could be decreased up to 100
      200 nm by reducing the expression time of the protein in vivo. CONCLUSIONS: To
      our knowledge, DL4 is the first GFP variant that folds correctly but aggregates
      exclusively in vivo without any self-aggregating/assembling tags. The fluorescent
      DL4 IBs have potentials to be used as fluorescent biomaterials. This study also
      suggests that biologically active IBs can be achieved through engineering a
      target protein itself.

PMID- 24885572
TI  - Maternal inheritance of an inactive type III deiodinase gene allele affects mouse
      pancreatic beta-cells and disrupts glucose homeostasis.
AB  - Dio3 is the most distal gene of the imprinted Dlk1-Dio3 gene locus and is
      expressed according to parental origin. Dio3 encodes the type 3 deiodinase (D3),
      a thioredoxin-fold like containing selenoenzyme that inactivates thyroid hormone
      and dampens thyroid hormone signaling. Here we used heterozygous animals with
      disruption of the Dio3 gene to study the allelic expression pattern of Dio3 in
      pancreatic beta-cells and the metabolic phenotype resulting from its
      inactivation. Adult heterozygous mice with disruption of the Dio3 gene with
      maternal inheritance of the inactive Dio3 allele exhibited a total loss of D3
      activity in isolated pancreatic islets, approximately 30% reduction in total
      pancreatic islet area, a marked decrease in insulin2 mRNA and in vivo glucose
      intolerance. In contrast, inheritance of the inactive Dio3 allele from the father
      did not affect D3 activity in isolated pancreatic islets and did not result in a
      pancreatic phenotype. Furthermore, exposure of pancreatic explants, D3-expressing
      MIN6-C3 cells or isolated pancreatic islets to 100 nM T3 for 24 hours reduced
      insulin2 mRNA by approximately 50% and the peak of glucose-induced insulin
      secretion. An unbiased analysis of T3-treated pancreatic islets revealed the down
      regulation of 21 gene sets (false discovery rate q value < 25%) involved in
      nucleolar function and transcription of rRNA, ribonucleotide binding, mRNA
      translation, and membrane organization. We conclude that the Dio3 gene is
      preferentially expressed from the maternal allele in pancreatic islets and that
      the inactivation of this allele is sufficient to disrupt glucose homeostasis by
      reducing the pancreatic islet area, insulin2 gene expression, and glucose
      stimulated insulin secretion. 

PMID- 24885573
TI  - Orphan nuclear receptor Nur77 mediates fasting-induced hepatic fibroblast growth
      factor 21 expression.
AB  - The fasting-induced hepatic hormone, fibroblast growth factor 21 (FGF21), is a
      potential candidate for the treatment of metabolic syndromes. Although peroxisome
      proliferator-activated receptor (PPAR)alpha is known to play a major role in the
      induction of hepatic FGF21 expression, other fasting-induced transcription
      factors that induce FGF21 expression have not yet been fully studied. In the
      present study, we investigated whether the fasting-induced activation of the
      orphan nuclear receptor Nur77 increases hepatic FGF21 expression. We found that
      fasting induced hepatic Nur77 and FGF21 expression. Glucagon and forskolin
      increased Nur77 and FGF21 expression in vivo and in vitro, respectively, and
      adenovirus-mediated overexpression of Nur77 (Ad-Nur77) increased FGF21 expression
      in vitro and in vivo. Moreover, knockdown of endogenous Nur77 expression by siRNA
      Nur77 abolished the effect of forskolin on FGF21 expression. The results of ChIP
      assays, EMSA, and mutagenesis analysis showed that Nur77 bound to the putative
      NBRE of the FGF21 promoter in cultured hepatocytes and fasting induced Nur77
      binding to the FGF21 promoter in vivo. Knockdown of PPARalpha partially inhibited
      forskolin-induced FGF21 expression, suggesting PPARalpha involvement in glucagon
      stimulated FGF21 expression. In addition, double knockdown of PPARalpha and Nur77
      further diminished FGF21 expression in cultured hepatocytes. In conclusion, this
      study shows that Nur77 mediates fasting-induced hepatic FGF21 expression, and
      suggests an alternative mechanism via which hepatic FGF21 transcription is
      mediated under fasting conditions. 

PMID- 24885574
TI  - Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite
      preserved gonadotropin secretion.
AB  - Premature ovarian failure (POF) affects 1% of women in reproductive age, but its
      etiology remains uncertain. Whereas kisspeptins, the products of Kiss1 that act
      via Kiss1r (aka, Gpr54), are known to operate at the hypothalamus to control
      GnRH/gonadotropin secretion, additional actions at other reproductive organs,
      including the ovary, have been proposed. Yet, their physiological relevance is
      still unclear. We present here a series of studies in Kiss1r haplo-insufficient
      and null mice suggesting a direct role of kisspeptin signaling in the ovary, the
      defect of which precipitates a state of primary POF. Kiss1r hypomorph mice
      displayed a premature decline in ovulatory rate, followed by progressive loss of
      antral follicles, oocyte loss, and a reduction in all categories of preantral
      follicles. These alterations were accompanied by reduced fertility. Because of
      this precocious ovarian ageing, mice more than 48 weeks of age showed atrophic
      ovaries, lacking growing follicles and corpora lutea. This phenomenon was
      associated with a drop in ovarian Kiss1r mRNA expression, but took place in the
      absence of a decrease in circulating gonadotropins. In fact, FSH levels increased
      in aged hypomorph animals, reflecting loss of follicular function. In turn,
      Kiss1r-null mice, which do not spontaneously ovulate and have arrested follicular
      development, failed to show normal ovulatory responses to standard gonadotropin
      priming and required GnRH prestimulation during 1 week in order to display
      gonadotropin-induced ovulation. Yet, the magnitude of such ovulatory responses
      was approximately half of that seen in control immature wild-type animals.
      Altogether, our data are the first to demonstrate that Kiss1r haplo-insufficiency
      induces a state of POF, which is not attributable to defective gonadotropin
      secretion. We also show that the failure of follicular development and ovulation
      linked to the absence of Kiss1r cannot be fully rescued by (even extended)
      gonadotropin replacement. These findings suggest a direct ovarian role of
      kisspeptin signaling, the perturbation of which may contribute to the
      pathogenesis of POF. 

PMID- 24885576
TI  - Perinatal mortality by gestational week and size at birth in singleton
      pregnancies at and beyond term: a nationwide population-based cohort study.
AB  - BACKGROUND: Whether gestational age per se increases perinatal mortality in post
      term pregnancy is unclear. We aimed at assessing gestational week specific
      perinatal mortality in small-for-gestational-age (SGA) and non-SGA term and post
      term gestations, and specifically to evaluate whether the relation between post
      term gestation and perinatal mortality differed before and after ultrasound was
      introduced as the standard method of gestational age estimation. METHODS: A
      population-based cohort study, using data from the Medical Birth Registry of
      Norway (MBRN), 1967-2006, was designed. Singleton births at 37 through 44
      gestational weeks (n = 1 855 682), excluding preeclampsia, diabetes and fetal
      anomalies, were included. Odds ratios (OR) with 95% confidence intervals (CI) for
      perinatal mortality and stillbirth in SGA and non-SGA births by gestational week
      were calculated. RESULTS: SGA infants judged post-term by LMP had significantly
      higher perinatal mortality than post-term non-SGA infants at 40 weeks,
      independent of time period (highest during 1999-2006 [OR 9.8, 95% CI: 5.7-17.0]).
      When comparing years before (1967-1986) versus after (1987-2006) ultrasound was
      introduced, there was no decrease in the excess mortality for post-term SGA
      versus non-SGA births (ORs from 6.1 [95% CI: 5.2-7.1] to 6.7 [5.2-8.5]), while
      mortality at 40 weeks decreased significantly (ORs from 4.6, [4.0-5.3] to 3.2
      [2.5-3.9]). When assessing stillbirth risk (1999-2006), more than 40% of SGA
      stillbirths (11/26) judged to be >=41 weeks by LMP were shifted to lower
      gestational ages using ultrasound estimation. CONCLUSIONS: Mortality risk in post
      term infants was strongly associated with growth restriction. Such infants may
      erroneously be judged younger than they are when using ultrasound estimation, so
      that the routine assessment for fetal wellbeing in the prolonged gestation may be
      given too late.

PMID- 24885575
TI  - Minireview: transgenerational epigenetic inheritance: focus on endocrine
      disrupting compounds.
AB  - The idea that what we eat, feel, and experience influences our physical and
      mental state and can be transmitted to our offspring and even to subsequent
      generations has been in the popular realm for a long time. In addition to classic
      gene mutations, we now recognize that some mechanisms for inheritance do not
      require changes in DNA. The field of epigenetics has provided a new appreciation
      for the variety of ways biological traits can be transmitted to subsequent
      generations. Thus, transgenerational epigenetic inheritance has emerged as a new
      area of research. We have four goals for this minireview. First, we describe the
      topic and some of the nomenclature used in the literature. Second, we explain the
      major epigenetic mechanisms implicated in transgenerational inheritance. Next, we
      examine some of the best examples of transgenerational epigenetic inheritance,
      with an emphasis on those produced by exposing the parental generation to
      endocrine-disrupting compounds (EDCs). Finally, we discuss how whole-genome
      profiling approaches can be used to identify aberrant epigenomic features and
      gain insight into the mechanism of EDC-mediated transgenerational epigenetic
      inheritance. Our goal is to educate readers about the range of possible
      epigenetic mechanisms that exist and encourage researchers to think broadly and
      apply multiple genomic and epigenomic technologies to their work. 

PMID- 24885578
TI  - An examination of the heterosexism scale.
AB  - Researchers explored the factor structure of Park's Heterosexism Scale (2001)
      with heterosexual parents of lesbian, gay, or bisexual sons or daughters. Results
      suggested a two-factor solution, but results varied from Park's two-factor model.
      Additionally, relations between the Heterosexism Scale subscales and measures of
      cognitive flexibility, religious commitment, and general family functioning were
      examined. Implications for clinical practice and future research are discussed. 

PMID- 24885577
TI  - Adherence to the cervical cancer screening program in women living with HIV in
      Denmark: comparison with the general population.
AB  - BACKGROUND: Women living with HIV (WLWH) are at increased risk of invasive
      cervical cancer (ICC). International HIV guidelines suggest cervical screening
      twice the first year after HIV diagnosis and thereafter annually. Adherence to
      the HIV cervical screening program in Denmark is unknown. METHODS: We studied
      women from a population-based, nationwide HIV cohort in Denmark and a cohort of
      age-matched females from the general population. Screening behaviour was assessed
      from 1999-2010. Adjusted odds ratios (OR's) for screening attendance in the two
      cohorts and potential predictors of attendance to guidelines were estimated.
      Pathology specimens were identified from The Danish Pathology Data Bank. RESULTS:
      We followed 1143 WLWH and 17,145 controls with no prior history of ICC for 9,509
      and 157,362 person-years. The first year after HIV diagnosis 2.6% of WLWH
      obtained the recommended two cervical cytologies. During the different calendar
      intervals throughout the study period between 29-46% of WLWH followed the HIV
      cervical screening guidelines. Adjusted OR's of attendance to the general
      population screening program for WLWH aged 30, 40 and 50 years, compared to
      controls, were 0.69 (95% CI: 0.56-0.87), 0.67 (0.55-0.80) and 0.84 (0.61-1.15).
      Predictors of attendance to the HIV cervical screening program were a CD4 count >
      350 cells/MUL and HIV RNA < 500 copies/mL. Calendar period after 2002 and HIV RNA
      < 500 copies/mL predicted attendance to the general population cervical screening
      program. CONCLUSIONS: The majority of WLWH do not follow the HIV guidelines for
      cervical screening. We support the idea of cytology as part of an annual review
      and integration of HIV care and cervical screening in a single clinic setting.

PMID- 24885579
TI  - Prevalence and sociodemographic trends of weight misperception in Korean
      adolescents.
AB  - BACKGROUND: Rapid physical and emotional growth occurs during youth. Adolescence
      is one of the most important periods for adapting to body change and establishing
      an ideal body image. Body change is an important and sensitive concern for
      adolescents, and the values and self-conception established at this time affect
      various aspects of the entire life. This study aimed to investigate the
      prevalence and trends of weight misperception among adolescents in Korea.
      METHODS: We analyzed raw data from the 2011 Korea Youth Risk Behaviour Web-based
      Survey-VII (KYRBWS-VII), in which 73,474 adolescents from the middle-school first
      grade to the high-school third grade (aged 12-18) participated. For the
      multivariate logistic regression model, the dependent variable was existence of
      misperception (yes/no) and independent variables were sociodemographic factors.
      RESULTS: We found that the prevalence of weight misperception was 49.3%
      (overestimation, 23.7%; underestimation, 25.6%). Among male students, 65.0%
      underestimated their weight, whereas 62.2% of female students overestimated their
      weight. Multivariate logistic regression analysis revealed that gender (OR =
      1.254; 95% CI = 1.214-1.294; p < 0.001) and socioeconomic status (OR = 1.173; 95%
      CI = 1.121-1.228; p < 0.001) were significantly associated with weight
      misperception. Compared with overweight/obese adolescents, adolescents whose BMI
      based body weight was underweight or normal showed 2.386-times higher (OR =
      2.386; 95% CI = 2.045-2.783, p < 0.001) and 32.804-times higher (OR = 32.804; 95%
      CI = 29.829-36.077, p < 0.001) body shape misperception, respectively.
      CONCLUSIONS: An effective obesity intervention program for adolescents must
      reflect and monitor body shape perception as well as BMI, and should include
      subjects who overestimate as well as underestimate their weight.

PMID- 24885580
TI  - Visfatin induces MUC8 and MUC5B expression via p38 MAPK/ROS/NF-kappaB in human
      airway epithelial cells.
AB  - BACKGROUND: Among a variety of inflammatory mediators, visfatin is a
      proinflammatory adipocytokine associated with inflammatory reactions in obesity,
      metabolic syndrome, chronic inflammatory disease, and autoimmune disease.
      However, the biological role of visfatin in secretion of major mucins in human
      airway epithelial cells has not been reported. Therefore, this study was
      conducted in order to investigate the effect and the brief signaling pathway of
      visfatin on MUC8 and MUC5B expression in human airway epithelial cells. RESULTS:
      Visfatin significantly induced MUC8 and MUC5B expression. Visfatin significantly
      activated phosphorylation of p38 MAPK. Treatment with SB203580 (p38 MAPK
      inhibitor) and knockdown of p38 MAPK by siRNA significantly blocked visfatin
      induced MUC8 and MUC5B expression.Visfatin significantly increased ROS formation.
      Treatment with SB203580 significantly attenuated visfatin-induced ROS formation.
      Treatment with NAC (ROS scavenger) and DPI (NADPH oxidase inhibitor)
      significantly attenuated visfatin-induced MUC8 and MUC5B expression. However,
      treatment with NAC and DPI did not attenuate visfatin-activated phosphorylation
      of p38 MAPK. Visfatin significantly activated the phosphorylation of NF-kappaB.
      Treatment with PDTC (NF-kappaB inhibitor) significantly attenuated visfatin
      induced MUC8 and MUC5B expression. CONCLUSIONS: These results suggest that
      visfatin induces MUC8 and MUC5B expression through p38 MAPK/ROS/NF-kappaB
      signaling pathway in human airway epithelial cells.

PMID- 24885581
TI  - Clinicopathological analysis of thymic malignancies with a consistent
      retrospective database in a single institution: from Tokyo Metropolitan Cancer
      Center.
AB  - BACKGROUND: Thymic epithelial tumors (TETs), which comprise thymoma and thymic
      carcinoma, are rare cancers with specific morphological and clinical features.
      Their clinical characteristics and outcomes have gradually been clarified by
      assessing large-scale, retrospective data obtained with international
      cooperation. METHODS: The study is a retrospective review of 187 Japanese
      patients with TETs who attended our institution from 1976 to 2012. Relevant
      clinical features of patients with TETs and their tumors, including histology,
      staging, treatment strategies, and overall survival, were investigated.
      Differences in survival were assessed by the Kaplan-Meier method and uni- and
      multi-variate Cox proportional hazards regression analyses. RESULTS: The 187
      patients included 52 patients with stage I, 37 with stage II, 22 with stage III,
      and 76 with stage IVa/IVb tumors according to the Masaoka-Koga Staging System. As
      to histological type, five patients had type A, 33 type AB, 19 type B1, 39 type
      B2, and 15 type B3 thymomas, whereas 68 patients had thymic carcinoma, including
      11 with neuroendocrine carcinomas according to the 2004 WHO classification.
      Either insufficient data were available to classify the tumors of the remaining
      eight patients or they had rare types. Immunological abnormalities were present
      in 26 patients, most of whom had thymomas (21.8% of the thymoma group). Most of
      the patients who presented with symptoms had myasthenia gravis or extensive
      thymic carcinoma. Secondary cancers were present in 25 patients (13.3%). The
      overall 5- and 10-year survival rates for thymoma were 85.4 and 71.5%,
      respectively, and those for thymic carcinoma were 33.8 and 2.3%, respectively. OS
      differed significantly between stage IVa thymomas and thymic carcinomas. The
      stage and whether the tumors were thymomas or thymic carcinomas were significant
      determinants of survival according to multivariate analysis. CONCLUSION: The
      efficacy of treatments for thymoma and thymic carcinoma should be investigated
      separately because these tumors differ in their clinical features and prognosis.

PMID- 24885582
TI  - Primary mucin-producing urothelial-type adenocarcinoma of the prostatic urethra
      diagnosed on TURP: a case report and review of literature.
AB  - BACKGROUND: Mucin-producing urothelial-type adenocarcinoma of the prostatic
      urethra is extremely rare. These lesions must be differentiated from other
      mucinous tumors including mucin-producing prostatic adenocarcinoma and metastases
      from either colonic or bladder primaries. CASE PRESENTATION: We report here a
      case of urothelial-type adenocarcinoma arising from the prostatic urethra. The
      patient is an 81 year-old man with a history of pT1 urothelial cell carcinoma of
      the bladder status post trans-urethral resection of bladder tumor (TURBT) who
      initially presented with irritative lower urinary tract symptoms and mucosuria
      refractory to Flomax and finasteride. A shared decision was made for the patient
      to undergo trans-urethral resection of prostate (TURP). At the time of surgery, a
      papillary tumor emanating from the prostatic urethra was found and no urothelial
      lesions were noted in the bladder. Pathology of the resected prostatic chips
      revealed an invasive adenocarcinoma with intestinal-type differentiation that
      stained positive for CK7, CK20, and villin, but negative for PSA, PSAP,
      uroplakin, and CDX-2. Colonoscopy was normal and CT scan did not show any
      evidence of colonic lesions nor visceral or lymph node metastases. Thus, the
      patient was diagnosed with a primary urothelial-type adenocarcinoma of the
      prostatic urethra. CONCLUSION: Herein we review the literature regarding this
      unusual entity, and discuss the differential diagnosis, immunohistochemistry, and
      the importance of correctly identifying this rare tumor.

PMID- 24885583
TI  - Quantification of tumour budding, lymphatic vessel density and invasion through
      image analysis in colorectal cancer.
AB  - BACKGROUND: Tumour budding (TB), lymphatic vessel density (LVD) and lymphatic
      vessel invasion (LVI) have shown promise as prognostic factors in colorectal
      cancer (CRC) but reproducibility using conventional histopathology is
      challenging. We demonstrate image analysis methodology to quantify the
      histopathological features which could permit standardisation across institutes
      and aid risk stratification of Dukes B patients. METHODS: Multiplexed
      immunofluorescence of pan-cytokeratin, D2-40 and DAPI identified epithelium,
      lymphatic vessels and all nuclei respectively in tissue sections from 50 patients
      diagnosed with Dukes A (n = 13), Dukes B (n = 29) and Dukes C (n = 8) CRC. An
      image analysis algorithm was developed and performed, on digitised images of the
      CRC tissue sections, to quantify TB, LVD, and LVI at the invasive front. RESULTS:
      TB (HR =5.7; 95% CI, 2.38-13.8), LVD (HR =5.1; 95% CI, 2.04-12.99) and LVI (HR
      =9.9; 95% CI, 3.57-27.98) were successfully quantified through image analysis and
      all were shown to be significantly associated with poor survival, in univariate
      analyses. LVI (HR =6.08; 95% CI, 1.17-31.41) is an independent prognostic factor
      within the study and was correlated to both TB (Pearson r =0.71, p <0.0003) and
      LVD (Pearson r =0.69, p <0.0003). CONCLUSION: We demonstrate methodology through
      image analysis which can standardise the quantification of TB, LVD and LVI from a
      single tissue section while decreasing observer variability. We suggest this
      technology is capable of stratifying a high risk Dukes B CRC subpopulation and we
      show the three histopathological features to be of prognostic significance.

PMID- 24885584
TI  - Knowledge about tooth avulsion and its management among dental assistants in
      Riyadh, Saudi Arabia.
AB  - BACKGROUND: Studies evaluating dental assistants' knowledge about tooth avulsion
      and its management are rare. The purpose of this study was to evaluate the level
      of knowledge about tooth avulsion and its management among dental assistants in
      Riyadh, Saudi Arabia and to assess its relationship with their educational
      background. METHODS: A convenience sampling methodology was employed for sample
      selection. Over a period of four months starting in February, 2013, 691 pretested
      17-item questionnaires were distributed. A total of 498 questionnaires were
      returned for an overall response rate of 72.1%. Six questions were related to
      knowledge about permanent tooth avulsion and one question was related to
      knowledge about primary tooth avulsion. Correct answers to these questions were
      assigned one point each, and based on this scoring system, an overall knowledge
      score was calculated. An analysis of covariance was used to test the association
      between the level of knowledge (total score) and the educational qualifications
      of the respondents (dental degree and others). A P-value of 0.05 was considered
      the threshold for statistical significance. RESULTS: The majority of the
      respondents (n = 387; 77.7%) were non-Saudis (377 were from the Philippines), and
      79.1% (n = 306) of the Filipinos had a dental degree. The question about
      recommendations for an avulsed tooth that is dirty elicited the highest number of
      correct responses (n = 444; 89.2%), whereas the question about the best storage
      media elicited the lowest number of correct responses (n = 192; 38.6%). The
      overall mean score for knowledge about tooth avulsion was 6.27 +/- 1.74. The mean
      knowledge score among the respondents with a dental degree was 6.63 +/- 1.37,
      whereas that among the respondents with other qualifications was 5.71 +/- 2.08.
      CONCLUSIONS: The educational qualifications of the surveyed dental assistants
      were strongly correlated with the level of knowledge about tooth avulsion and its
      management.

PMID- 24885585
TI  - The protocol and design of a randomised controlled study on training of attention
      within the first year after acquired brain injury.
AB  - BACKGROUND: To describe the design of the study aiming to examine intensive
      targeted cognitive rehabilitation of attention in the acute (<4 months) and
      subacute rehabilitation phases (4-12 months) after acquired brain injury and to
      evaluate the effects on function, activity and participation (return to work).
      METHODS/DESIGN: Within a prospective, randomised, controlled study 120
      consecutive patients with stroke or traumatic brain injury were randomised to 20
      hours of intensive attention training by Attention Process Training or by
      standard, activity based training. Progress was evaluated by Statistical Process
      Control and by pre and post measurement of functional and activity levels. Return
      to work was also evaluated in the post-acute phase. Primary endpoints were the
      changes in the attention measure, Paced Auditory Serial Addition Test and changes
      in work ability. Secondary endpoints included measurement of cognitive functions,
      activity and work return. There were 3, 6 and 12-month follow ups focussing on
      health economics. DISCUSSION: The study will provide information on
      rehabilitation of attention in the early phases after ABI; effects on function,
      activity and return to work. Further, the application of Statistical Process
      Control might enable closer investigation of the cognitive changes after acquired
      brain injury and demonstrate the usefulness of process measures in
      rehabilitation. The study was registered at ClinicalTrials.gov Protocol. TRIAL
      REGISTRATION: NCT02091453, registered: 19 March 2014.

PMID- 24885586
TI  - Medicinal plants used in traditional medicine by Oromo people, Ghimbi District,
      Southwest Ethiopia.
AB  - BACKGROUND: Ethiopia is one of the six centres of biodiversity in the world with
      several topographies, climatic conditions and various ethnic cultures.
      Ethnobotanical study is a real and encourageable in rich biological resource
      areas for medicinal plant identification, documentation, ranking, conservation
      and sustainable usages. The purpose of this study was to identify the most
      effective medicinal plants for specific treatment through priority ranking and to
      assess the status of the transfer of Traditional Botanical Knowledge (TBK) based
      on age groups and educational levels. METHODOLOGY: Ethnobotanical data were
      collected using field observation and semi-structured interview, A total of 30
      key informants and 165 community members were interviewed and data on medicinal
      plant species and associated knowledge were recorded, quantified and verified
      using several preference ranking methods. RESULTS: The study revealed a total of
      49 medicinal plant species (belonging to 31 families and 46 genera) used to treat
      various human ailments, the majority of which 40 (81.6%) species were collected
      from wild while the rests from home garden. Herbs constituted the largest growth
      habit (18 species, 37%) followed by trees (16 species, 32%) and shrubs (15
      species, 31%). Leaf '17 (35%) is the plant part widely used followed by root 13
      (27%), leafy-stem 5 (10%), and seed 6 (12%). Oral administration was the dominant
      route (63%), followed by dermal route (22%) and nasal (11%). The highest number
      of plant species being used for infectious (48%) followed by two or more diseases
      and non-infectious disease. Of five and seven medicinal plants of preference
      ranking the highest ranks were given first for Croton macrostaychus used for
      malaria treatment and for Prunus africana as ''rare" for immediate collection and
      use in the traditional treatment. Significantly higher average number of
      medicinal plants (p < 0.05) were reported by informants of higher institution
      (14.3 +/- 34) and adult age groups (11.6 +/- 43). CONCLUSION: The Ghimbi people
      possess rich ethno-medicinal knowledge. This study can be used as a basis for
      developing management plans for conservation, sustainable use and drug
      development.

PMID- 24885588
TI  - Micropatterned ferrocenyl monolayers covalently bound to hydrogen-terminated
      silicon surfaces: effects of pattern size on the cyclic voltammetry and
      capacitance characteristics.
AB  - The effect of the size of patterns of micropatterned ferrocene (Fc)
      functionalized, oxide-free n-type Si(111) surfaces was systematically
      investigated by electrochemical methods. Microcontact printing with amine
      functionalized Fc derivatives was performed on a homogeneous acid fluoride
      terminated alkenyl monolayer covalently bound to n-type H-terminated Si surfaces
      to give Fc patterns of different sizes (5 * 5, 10 * 10, and 20 * 20 MUm(2)),
      followed by backfilling with n-butylamine. These Fc-micropatterned surfaces were
      characterized by static water contact angle measurements, ellipsometry, X-ray
      photoelectron spectroscopy (XPS), infrared reflection-absorption spectroscopy
      (IRRAS), atomic force microscopy (AFM), and scanning electron microscopy (SEM).
      The charge-transfer process between the Fc-micropatterned and underlying Si
      interface was subsequently studied by cyclic voltammetry and capacitance. By
      electrochemical studies, it is evident that the smallest electroactive ferrocenyl
      patterns (i.e., 5 * 5 MUm(2) squares) show ideal surface electrochemistry, which
      is characterized by narrow, perfectly symmetric, and intense cyclic voltammetry
      and capacitance peaks. In this respect, strategies are briefly discussed to
      further improve the development of photoswitchable charge storage microcells
      using the produced redox-active monolayers. 

PMID- 24885587
TI  - Saccharification and liquefaction of cassava starch: an alternative source for
      the production of bioethanol using amylolytic enzymes by double fermentation
      process.
AB  - BACKGROUND: Cassava starch is considered as a potential source for the commercial
      production of bioethanol because of its availability and low market price. It can
      be used as a basic source to support large-scale biological production of
      bioethanol using microbial amylases. With the progression and advancement in
      enzymology, starch liquefying and saccharifying enzymes are preferred for the
      conversion of complex starch polymer into various valuable metabolites. These
      hydrolytic enzymes can selectively cleave the internal linkages of starch
      molecule to produce free glucose which can be utilized to produce bioethanol by
      microbial fermentation. RESULTS: In the present study, several filamentous fungi
      were screened for production of amylases and among them Aspergillus fumigatus
      KIBGE-IB33 was selected based on maximum enzyme yield. Maximum alpha-amylase,
      amyloglucosidase and glucose formation was achieved after 03 days of fermentation
      using cassava starch. After salt precipitation, fold purification of alpha
      amylase and amyloglucosidase increased up to 4.1 and 4.2 times with specific
      activity of 9.2 kUmg-1 and 393 kUmg-1, respectively. Concentrated amylolytic
      enzyme mixture was incorporated in cassava starch slurry to give maximum glucose
      formation (40.0 gL-1), which was further fermented using Saccharomyces cerevisiae
      into bioethanol with 84.0% yield. The distillate originated after recovery of
      bioethanol gave 53.0% yield. CONCLUSION: An improved and effective dual enzymatic
      starch degradation method is designed for the production of bioethanol using
      cassava starch. The technique developed is more profitable due to its fast
      liquefaction and saccharification approach that was employed for the formation of
      glucose and ultimately resulted in higher yields of alcohol production.

PMID- 24885589
TI  - The effects of conjugate and light dose on photo-immunotherapy induced
      cytotoxicity.
AB  - BACKGROUND: Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy,
      which employs monoclonal antibodies conjugated to a potent photosensitizer (mAb
      IR700). Once the conjugate has bound to the target cell, exposure to near
      infrared (NIR) light induces necrosis only in targeted cells with minimal damage
      to adjacent normal cells in vivo. Herein, we report on the effect of altering mAb
      IR700 and light power and dose on effectiveness of PIT. METHODS: For evaluating
      cytotoxicity, we employed ATP-dependent bioluminescence imaging using a
      luciferase-transfected MDA-MB-468luc cell line, which expresses EGFR and
      luciferase. In in vitro experiments, panitumumab-IR700 (Pan-IR700) concentration
      was varied in combination with varying NIR light doses administered by an LED at
      one of three power settings, 100 mA and 400 mA continuous wave and 1733 mA
      intermittent wave. For in vivo experiments, the MDA-MB-468luc orthotopic breast
      cancer was treated with varying doses of Pan-IR700 and light. RESULTS: The in
      vitro cell study demonstrated that PIT induced cytotoxicity depended on light
      dose, when the conjugate concentration was kept constant. Increasing the dose of
      Pan-IR700 allowed lowering of the light dose to achieve equal effects thus
      indicating that for a given level of efficacy, the conjugate concentration
      multiplied by the light dose was a constant. A similar relationship between
      conjugate and light dose was observed in vivo. CONCLUSIONS: The efficacy of PIT
      is defined by the product of the number of bound antibody conjugates and the dose
      of NIR light and can be achieve equally with continuous and pulse wave LED light
      using different power densities.

PMID- 24885590
TI  - Network-meta analysis made easy: detection of inconsistency using factorial
      analysis-of-variance models.
AB  - BACKGROUND: Network meta-analysis can be used to combine results from several
      randomized trials involving more than two treatments. Potential inconsistency
      among different types of trial (designs) differing in the set of treatments
      tested is a major challenge, and application of procedures for detecting and
      locating inconsistency in trial networks is a key step in the conduct of such
      analyses. METHODS: Network meta-analysis can be very conveniently performed using
      factorial analysis-of-variance methods. Inconsistency can be scrutinized by
      inspecting the design * treatment interaction. This approach is in many ways
      simpler to implement than the more common approach of using treatment-versus
      control contrasts. RESULTS: We show that standard regression diagnostics
      available in common linear mixed model packages can be used to detect and locate
      inconsistency in trial networks. Moreover, a suitable definition of factors and
      effects allows devising significance tests for inconsistency. CONCLUSION:
      Factorial analysis of variance provides a convenient framework for conducting
      network meta-analysis, including diagnostic checks for inconsistency.

PMID- 24885591
TI  - "Getting stuck with LAM": patients perspectives on living with
      lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease
      that affects almost exclusively women and is most often diagnosed before
      menopause. The main symptom of LAM is shortness of breath. LAM patients'
      perceptions of how the disease impacts their lives is largely unknown, but such
      information could be useful to generate patient reported outcome measures for use
      in drug trials (or other research studies) and to formulate interventions aimed
      at easing the burdens LAM imposes on patients. OBJECTIVE: To capture patients'
      perceptions of how LAM affects their lives. METHODS: We used reflexive team
      analysis to analyze transcripts from semi-structured focus groups conducted with
      LAM patients at LAMposium 2013. We sought to determine what patients perceive as
      the primary symptoms of LAM and how the disease affects them in their daily
      lives. RESULTS: The 37 participants described seven primary symptoms of LAM and
      five common psychological experiences from living with the disease. Shortness of
      breath and low energy (or fatigue) dominated the symptomatic picture; cough,
      sensations in the chest, difficulty sleeping, gastrointestinal issues, and mild
      cognitive difficulties were less common. The common psychological experiences
      participants reported included frustration, worry, loss of identity,
      embarrassment, and in some participants, a healthy defiance against the disease.
      CONCLUSIONS: Patients perceive the physical symptoms from LAM to be intrusive and
      limiting. Women living with LAM are frustrated by their physical limitations, and
      they worry about what the future will be like if the disease progresses.
      Therapeutic interventions should take aim at improving these perceptions.

PMID- 24885592
TI  - Three-dimensional canine displacement patterns in response to translation and
      controlled tipping retraction strategies.
AB  - OBJECTIVE: To validate whether applying a well-defined initial three-dimensional
      (3D) load can create consistently expected tooth movement in patients. MATERIALS
      AND METHODS: Twenty-one patients who needed bilateral canine retraction to close
      extraction space were selected for this split-mouth clinical trial. After initial
      alignment and leveling, two canines in each patient were randomly assigned to
      receive either translation (TR) or controlled tipping (CT) load. The load was
      delivered by segmental T-loops designed to give specific initial moment/force
      ratios to the canines in each treatment interval (TI), verified with an
      orthodontic force tester. Maxillary dental casts were made before canine
      retraction and after each TI. The casts were digitized with a 3D laser scanner.
      The digital models were superimposed on the palatal rugae region. The 3D canine
      displacements and the displacement patterns in terms of TR, CT, and torque were
      calculated for each TI. RESULTS: The method can reliably detect a TR displacement
      greater than 0.3 mm and a rotation greater than 1.5 degrees . Ninety-two TIs had
      displacements that were greater than 0.3 mm and were used for further analysis.
      Most displacements were oriented within +/-45 degrees  from the distal direction.
      The displacement pattern in terms of TR or CT was not uniquely controlled by the
      initial moment/force ratio. CONCLUSIONS: The initial load system is not the only
      key factor controlling tooth movement. Using a segmental T-loop with a well
      controlled load system, large variations in canine displacement can be expected
      clinically.

PMID- 24885593
TI  - Responsiveness of the individual work performance questionnaire.
AB  - BACKGROUND: Individual work performance is an important outcome measure in
      studies in the workplace. Nevertheless, its conceptualization and measurement has
      proven challenging. To overcome limitations of existing scales, the Individual
      Work Performance Questionnaire (IWPQ) was recently developed. The aim of the
      current study was to gain insight into the responsiveness of the IWPQ. METHODS:
      Data were used from the Be Active & Relax randomized controlled trial. The aim of
      the trial was to investigate the effectiveness of an intervention to stimulate
      physical activity and relaxation of office workers, on need for recovery.
      Individual work performance was a secondary outcome measure of the trial. In
      total, 39 hypotheses were formulated concerning correlations between changes on
      the IWPQ scales and changes on similar constructs (e.g., presenteeism) and
      distinct constructs (e.g., need for recovery) used in the trial. RESULTS: 260
      Participants completed the IWPQ at both baseline and 12 months of follow-up. For
      the IWPQ scales, 23%, 15%, and 38%, respectively, of the hypotheses could be
      confirmed. In general, the correlations between change scores were weaker than
      expected. Nevertheless, at least 85% of the correlations were in the expected
      direction. CONCLUSIONS: Based on results of the current study, no firm
      conclusions can be drawn about the responsiveness of the IWPQ. Several reasons
      may account for the weaker than expected correlations. Future research on the
      IWPQ's responsiveness should be conducted, preferably in other populations and
      intervention studies, where greater changes over time can be expected.

PMID- 24885594
TI  - Discrepant alterations in main candidate genes among multiple primary melanomas.
AB  - BACKGROUND: Alterations in key-regulator genes of disease pathogenesis (BRAF,
      cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma
      (MPM). METHODS: One hundred twelve MPM patients (96 cases with two primary
      melanomas, 15 with three, and 1 with four) were included into the study. Paired
      synchronous/asynchronous MPM tissues (N=229) were analyzed for BRAF mutations and
      cKIT/CyclynD1 gene amplifications. RESULTS: BRAF mutations were identified in
      109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were
      observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While
      frequency rates of BRAF mutations were quite identical across the different MPM
      lesions, a significant increase of cKIT (p<0.001) and CyclinD1 (p=0.002)
      amplification rates was observed between first and subsequent primary melanomas.
      Among the 107 patients with paired melanoma samples, 53 (49.5%) presented
      consistent alteration patterns between first and subsequent primary tumors. About
      one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern
      of BRAF mutations as compared to incident primary tumors. CONCLUSIONS: The low
      consistency in somatic mutation patterns among MPM lesions from same patients
      provides further evidence that melanomagenesis is heterogeneous and different
      cell types may be involved. This may have implications in clinical practice due
      to the difficulties in molecularly classifying patients with discrepant primary
      melanomas.

PMID- 24885595
TI  - Matrix metalloproteinase-10 promotes tumor progression through regulation of
      angiogenic and apoptotic pathways in cervical tumors.
AB  - BACKGROUND: Cancer invasion and metastasis develops through a series of steps
      that involve the loss of cell to cell and cell to matrix adhesion, degradation of
      extracellular matrix and induction of angiogenesis. Different protease systems
      (e.g., matrix metalloproteinases, MMPs) are involved in these steps. MMP-10, one
      of the lesser studied MMPs, is limited to epithelial cells and can facilitate
      tumor cell invasion by targeting collagen, elastin and laminin. Enhanced MMP-10
      expression has been linked to poor clinical prognosis in some cancers, however,
      mechanisms underlying a role for MMP-10 in tumorigenesis and progression remain
      largely unknown. Here, we report that MMP-10 expression is positively correlated
      with the invasiveness of human cervical and bladder cancers. METHODS: Using
      commercial tissue microarray (TMA) of cervical and bladder tissues, MMP-10
      immunohistochemical staining was performed. Furthermore using a panel of human
      cells (HeLa and UROtsa), in vitro and in vivo experiments were performed in which
      MMP-10 was overexpressed or silenced and we noted phenotypic and genotypic
      changes. RESULTS: Experimentally, we showed that MMP-10 can regulate tumor cell
      migration and invasion, and endothelial cell tube formation, and that MMP-10
      effects are associated with a resistance to apoptosis. Further investigation
      revealed that increasing MMP-10 expression stimulates the expression of HIF
      1alpha and MMP-2 (pro-angiogenic factors) and PAI-1 and CXCR2 (pro-metastatic
      factors), and accordingly, targeting MMP-10 with siRNA in vivo resulted in
      diminution of xenograft tumor growth with a concomitant reduction of angiogenesis
      and a stimulation of apoptosis. CONCLUSION: Taken together, our findings show
      that MMP-10 can play a significant role in tumor growth and progression, and that
      MMP-10 perturbation may represent a rational strategy for cancer treatment.

PMID- 24885596
TI  - Mathematical modeling of the effects of glutathione on arsenic methylation.
AB  - BACKGROUND: Arsenic is a major environmental toxin that is detoxified in the
      liver by biochemical mechanisms that are still under study. In the traditional
      metabolic pathway, arsenic undergoes two methylation reactions, each followed by
      a reduction, after which it is exported and released in the urine. Recent
      experiments show that glutathione plays an important role in arsenic
      detoxification and an alternative biochemical pathway has been proposed in which
      arsenic is first conjugated by glutathione after which the conjugates are
      methylated. In addition, in rats arsenic-glutathione conjugates can be exported
      into the plasma and removed by the liver in the bile. METHODS: We have developed
      a mathematical model for arsenic biochemistry that includes three mechanisms by
      which glutathione affects arsenic methylation: glutathione increases the speed of
      the reduction steps; glutathione affects the activity of arsenic
      methyltranferase; glutathione sequesters inorganic arsenic and its methylated
      downstream products. The model is based as much as possible on the known
      biochemistry of arsenic methylation derived from cellular and experimental
      studies. RESULTS: We show that the model predicts and helps explain recent
      experimental data on the effects of glutathione on arsenic methylation. We
      explain why the experimental data imply that monomethyl arsonic acid inhibits the
      second methylation step. The model predicts time course data from recent
      experimental studies. We explain why increasing glutathione when it is low
      increases arsenic methylation and that at very high concentrations increasing
      glutathione decreases methylation. We explain why the possible temporal variation
      of the glutathione concentration affects the interpretation of experimental
      studies that last hours. CONCLUSIONS: The mathematical model aids in the
      interpretation of data from recent experimental studies and shows that the
      Challenger pathway of arsenic methylation, supplemented by the glutathione
      effects described above, is sufficient to understand and predict recent
      experimental data. More experimental studies are needed to explicate the detailed
      mechanisms of action of glutathione on arsenic methylation. Recent experimental
      work on the effects of glutathione on arsenic methylation and our modeling study
      suggest that supplements that increase hepatic glutathione production should be
      considered as strategies to reduce adverse health effects in affected
      populations.

PMID- 24885597
TI  - Retinal nerve fibre layer, ganglion cell layer and choroid thinning in migraine
      with aura.
AB  - BACKGROUND: The aim of this study was to investigate the thickness of the retinal
      nerve fiber layer (RNFL), the ganglion cell layer (GCL), and choroid thickness
      (CT) in patients who have migraines, with and without aura, using spectral
      optical coherence tomography (OCT). METHODS: Forty-five patients who had
      migraines without aura (Group 1), 45 patients who had migraines with aura (Group
      2), and 30 healthy participants (control group) were included in the study.
      Spectral OCT was used to measure the RNFL, GCL and CT values for all patients.
      RESULTS: The mean age of Group 1, Group 2, and the control group was 34.6 +/-
      4.3, 32.8 +/- 4.9, and 31.8 +/- 4.6 years, respectively. The mean attack
      frequency was 3.6/month in Group 1 and 3.7/month in Group 2. The mean age among
      the groups (p = 0.27) and number of attacks in migraine patients (p = 0.73) were
      not significantly different. There was significant thinning in the RNFL and GCL
      in Group 2 (p < 0.05, p < 0.001 respectively), while there were no significant
      differences in RNFL and GCL measurements between Group 1 and the control group (p
      > 0.05). All groups were significantly different from one another with respect to
      CT, with the most thinning observed in Group 2 (p < 0.001). When all migraine
      patients (without grouping) were compared with the control group, there were
      significant differences on all parameters: RNFL thickness, GCC thickness and CT
      (p < 0.05). CONCLUSIONS: RNFL and GCL were significantly thinner in the migraine
      patients with aura as compared with both the migraine patients without aura and
      the control subjects. In migraine, both with aura and without aura, patients'
      choroid thinning should be considered when evaluating ophthalmological findings.

PMID- 24885598
TI  - Trade-offs drive resource specialization and the gradual establishment of
      ecotypes.
AB  - BACKGROUND: Speciation is driven by many different factors. Among those are trade
      offs between different ways an organism utilizes resources, and these trade-offs
      can constrain the manner in which selection can optimize traits. Limited
      migration among allopatric populations and species interactions can also drive
      speciation, but here we ask if trade-offs alone are sufficient to drive
      speciation in the absence of other factors. RESULTS: We present a model to study
      the effects of trade-offs on specialization and adaptive radiation in asexual
      organisms based solely on competition for limiting resources, where trade-offs
      are stronger the greater an organism's ability to utilize resources. In this
      model resources are perfectly substitutable, and fitness is derived from the
      consumption of these resources. The model contains no spatial parameters, and is
      therefore strictly sympatric. We quantify the degree of specialization by the
      number of ecotypes evolved and the niche breadth of the population, and observe
      that these are sensitive to resource influx and trade-offs. Resource influx has a
      strong effect on the degree of specialization, with a clear transition between
      minimal diversification at high influx and multiple species evolving at low
      resource influx. At low resource influx the degree of specialization further
      depends on the strength of the trade-offs, with more ecotypes evolving the
      stronger trade-offs are. The specialized organisms persist through negative
      frequency-dependent selection. In addition, by analyzing one of the evolutionary
      radiations in greater detail we demonstrate that a single mutation alone is not
      enough to establish a new ecotype, even though phylogenetic reconstruction
      identifies that mutation as the branching point. Instead, it takes a series of
      additional mutations to ensure the stable coexistence of the new ecotype in the
      background of the existing ones. CONCLUSIONS: Trade-offs are sufficient to drive
      the evolution of specialization in sympatric asexual populations. Without trade
      offs to restrain traits, generalists evolve and diversity decreases. The
      observation that several mutations are required to complete speciation, even when
      a single mutation creates the new species, highlights the gradual nature of
      speciation and the importance of phyletic evolution.

PMID- 24885599
TI  - Types and drug susceptibility patterns of bacterial isolates from eye discharge
      samples at Gondar University Hospital, Northwest Ethiopia.
AB  - BACKGROUND: The type and pattern of organisms that cause ocular infection changes
      over time. Moreover, the causative organisms have developed increased drug
      resistance. Therefore, the aim of this study was to determine the prevalent
      bacterial agents of eye discharge and their drug susceptibility patterns to
      commonly used antimicrobial agents. METHODS: A retrospective study was conducted
      at Gondar University Hospital, Northwest Ethiopia from September, 2009 to August,
      2012. Culture and drug susceptibility test results of patients who had eye
      infections were taken for analysis. Eye discharge samples were cultured on
      MacConkey agar, blood agar and chocolate agar plates. A standard biochemical
      procedure was used for full identification of bacterial isolates. Antimicrobial
      susceptibility tests were done on Mueller-Hinton agar by using disk diffusion
      method. Data was entered and analyzed by using SPSS version 16 software. RESULT:
      A total of 102 eye discharges were submitted for microbiological evaluation, of
      which (60.8%) had bacterial growth. The most frequently isolated bacterial
      isolates were gram-positive bacteria (74.2%). The predominant bacterial species
      isolated was Coagulase-negative staphylococci (27.4%) followed by S. aureus
      (21%). Within the age group of 1 day-2 years old, (66.1%) of bacteria were
      isolated. Most of the bacterial isolates were resistance to ampicilin (71%),
      amoxicilin (62.9%), erythromycin (43.5%), gentamicin (45.2%), penicillin (71%),
      trimethoprim-sulphamethoxazole (58.1%), and tetracycline (64.6%) while Ceftriaxon
      and Ciprofloxacin showed (75.8%) and (80%) susceptibility respectively. From the
      total bacterial isolates, (87.1%) were showed multi drug resistance (MDR) to two
      or more drugs. CONCLUSION: The prevalence of bacterial isolates in eye discharge
      was high in the study area and majority of isolates were gram-positive bacteria.
      Most of the bacterial isolates were resistant to frequently used antimicrobials.
      Therefore, drug susceptibility test is necessary before prescribing any
      antimicrobials.

PMID- 24885602
TI  - A method for generating highly multiplexed ChIP-seq libraries.
AB  - BACKGROUND: The barcoding of next generation sequencing libraries has become an
      essential part of the experimental design. Barcoding not only allows the
      sequencing of more than one sample per lane, but also reduces technical bias.
      However, current barcoding strategies impose significant limitations and/or
      technical barriers in their implementation for ChIP-sequencing. FINDINGS:
      Converting Y-shaped sequencing adapters to double stranded DNA prior to agarose
      gel size selection reduces adapter dimer contamination and quantitating the
      number of cycles required for amplification of the library with qPCR prior to
      library amplification eliminates library over-amplification. CONCLUSIONS: We
      describe an efficient and cost effective method for making barcoded ChIP-seq
      libraries for sequencing on the Illumina platform.

PMID- 24885601
TI  - Development and psychometric properties of the Y-PASS questionnaire to assess
      correlates of lunchtime and after-school physical activity in children.
AB  - BACKGROUND: To frame interventions, it is useful to understand context- and time
      specific correlates of children's physical activity. To do this, we need accurate
      assessment of these correlates. There are currently no measures that assess
      correlates at all levels of the social ecological model, contain items that are
      specifically worded for the lunchtime and/or after-school time periods, and
      assess correlates that have been conceptualised and defined by children. The aim
      of this study was to develop and evaluate the psychometric properties of the
      lunchtime and after-school Youth Physical Activity Survey for Specific Settings
      (Y-PASS) questionnaires. METHODS: The Y-PASS questionnaire was administered to
      264 South Australian children (146 boys, 118 girls; mean age = 11.7 +/- 0.93
      years). Factorial structure and internal consistency of the intrapersonal,
      sociocultural and physical environmental/policy lunchtime and after-school
      subscales were examined through an exploratory factor analysis. The test-retest
      reliability of the Y-PASS subscales was assessed over a one-week period on a
      subsample of children (lunchtime Y-PASS: n = 12 boys, 12 girls, mean age of 11.6
      +/- 0.8 years; after-school Y-PASS: n = 9 boys, 13 girls; mean age = 11.4 +/- 0.9
      years). RESULTS: For the lunchtime Y-PASS, three factors were identified under
      each of the intrapersonal, sociocultural and physical environmental/policy
      subscales. For the after-school Y-PASS, six factors were identified in the
      intrapersonal subscale, four factors in the sociocultural subscale and seven
      factors in the physical environmental/policy subscale. Following item reduction,
      all subscales demonstrated acceptable internal consistency (Cronbach alpha = 0.78
      0.85), except for the lunchtime sociocultural subscale (Cronbach alpha = 0.55).
      The factors and items demonstrated fair to very high test-retest reliability (ICC
      = 0.26-0.93). CONCLUSION: The preliminary reliability and factorial structure
      evidence suggests the Y-PASS correlate questionnaires are robust tools for
      measuring correlates of context-specific physical activity in children. The multi
      dimensional factor structure provides justification for exploring physical
      activity correlates from a social ecological perspective and demonstrates the
      importance of developing items that are context specific. Further development and
      refinement of the Y-PASS questionnaires is recommended, including a confirmatory
      factor analysis and exploring the inclusion of additional items.

PMID- 24885600
TI  - The effectiveness of antioxidant vitamins C and E in reducing myocardial infarct
      size in patients subjected to percutaneous coronary angioplasty (PREVEC Trial):
      study protocol for a pilot randomized double-blind controlled trial.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of mortality
      worldwide. Oxidative stress has been involved in the ischemia-reperfusion injury
      in AMI. It has been suggested that reperfusion accounts for up to 50% of the
      final size of a myocardial infarct, a part of the damage likely to be
      prevented.Therefore, we propose that antioxidant reinforcement through vitamins C
      and E supplementation should protect against the ischemia-reperfusion damage,
      thus decreasing infarct size.The PREVEC Trial (Prevention of reperfusion damage
      associated with percutaneous coronary angioplasty following acute myocardial
      infarction) seeks to evaluate whether antioxidant vitamins C and E reduce infarct
      size in patients subjected to percutaneous coronary angioplasty after AMI.
      METHODS/DESIGN: This is a randomized, 1:1, double-blind, placebo-controlled
      clinical trial.The study takes place at two centers in Chile: University of Chile
      Clinical Hospital and San Borja Arriaran Clinical Hospital.The subjects will be
      134 adults with acute myocardial infarction with indication for percutaneous
      coronary angioplasty.This intervention is being performed as a pilot study,
      involving high-dose vitamin C infusion plus oral administration of vitamin E
      (Vitamin-treatment group) or placebo (Control group) during the angioplasty
      procedure. Afterward, the Vitamin-treatment group receives oral doses of vitamins
      C and E, and the Control group receives placebo for 84 days after coronary
      angioplasty.Primary outcome is infarct size, assessed by cardiac magnetic
      resonance (CMR), measured 6 and 84 days after coronary angioplasty.Secondary
      outcomes are ejection fraction, measured 6 and 84 days after coronary angioplasty
      with CMR, and biomarkers for oxidative stress, antioxidant status, heart damage,
      and inflammation, which will be measured at baseline, at the onset of
      reperfusion, 6 to 8 hours after revascularization, and at hospital discharge.
      DISCUSSION: The ischemia-reperfusion event occurring during angioplasty is known
      to increase myocardial infarct size. The cardioprotective benefits of high doses
      of vitamin C combined with vitamin E have not been fully explored. The PREVEC
      Trial seeks to determine the suitability of the therapeutic use of vitamins C and
      E against the reperfusion damage produced during angioplasty.Patient recruitment
      opened in February 2013. The trial is scheduled to end in March 2016. TRIAL
      REGISTRATION: ISRCTN56034553.

PMID- 24885603
TI  - Leukemoid reaction and autocrine growth of bladder cancer induced by
      paraneoplastic production of granulocyte colony-stimulating factor--a potential
      neoplastic marker: a case report and review of the literature.
AB  - INTRODUCTION: Granulocyte colony-stimulating factor produced by nonhematopoietic
      malignant cells is able to induce a leukemoid reaction by excessive stimulation
      of leukocyte production. Expression of granulocyte colony-stimulating factor and
      its functional receptors have been confirmed in bladder cancer cells. In vitro
      studies have demonstrated that granulocyte colony-stimulating factor/receptor
      exhibits a high affinity binding and this biological axis increases proliferation
      of the carcinoma. Urothelial carcinoma of the bladder is rarely associated with a
      leukemoid reaction and autocrine growth induced by paraneoplastic production of
      granulocyte colony-stimulating factor. In the world literature, there have been
      less than 35 cases reported in the last 35 years. The clinicopathological
      aspects, biology, prognosis and management of granulocyte colony-stimulating
      factor-secreting bladder cancers are poorly understood. CASE PRESENTATION: A 39
      year-old Caucasian woman with an invasive high-grade urothelial carcinoma
      presented with hematuria and low-grade fevers. Laboratory tests revealed an
      elevated white blood cell count and absolute neutrophil count and an elevated 24
      hour urine protein. Upon further evaluation she was found to have locally
      advanced high-grade urothelial carcinoma without nodal or distant metastasis. Her
      serum granulocyte colony-stimulating factor level was 10 times the normal limit.
      This led to the diagnosis of a paraneoplastic leukemoid reaction. Her white blood
      cell count immediately normalized after cystectomy but increased in concordance
      with recurrence of her disease. Unfortunately, she rapidly progressed and expired
      within 10 months from the time of first diagnosis. CONCLUSIONS: This is one of
      the few cases reported that illustrates the existence of a distinct and highly
      aggressive subtype of bladder cancer which secretes granulocyte colony
      stimulating factor. Patients presenting with a leukemoid reaction should be
      tested for granulocyte colony-stimulating factor/receptor biological axis.
      Moreover, granulocyte colony-stimulating factor could be a potential neoplastic
      marker as it can follow the clinical course of the underlying tumor and thus be
      useful for monitoring its evolution. Neoadjuvant chemotherapy should be
      considered in these patients due to the aggressive nature of these tumors. With a
      better understanding of the biology, this autocrine growth signal could be a
      potential target for therapy in future.

PMID- 24885605
TI  - Type 2 diabetes patients' perspectives on lifestyle counselling and weight
      management in general practice: a qualitative study.
AB  - BACKGROUND: Lifestyle counselling is a pivotal aspect of diabetes care. But
      general practitioners (GPs) often have problems in finding their role in
      patients' weight management. The aims of this study were to investigate the
      experiences of type 2 diabetes patients with lifestyle counselling from their GPs
      and to explore how patients' preferences regarding counselling are embedded in
      the context of self-management and wider cultural aspects of nutrition. METHODS:
      Narrative interviews were conducted with 35 people with type 2 diabetes aged
      between 35 and 77 years. The interviews were transcribed verbatim and analysed
      using the thematic framework method. RESULTS: Many patients had a strong feeling
      of personal responsibility for weight reduction as integral to diabetes self
      management but found it difficult to integrate the changes their disease requires
      into their self-management activities. They attached great importance to their
      GPs' advice on diet. While some patients appreciated direct communication, others
      regarded dramatic pictures as either unhelpful or offending. A serious problem
      was the incompatibility of the dietary recommendations with daily life resulting
      in a reluctance to adjust the whole diet to the needs of diabetes care.
      CONCLUSIONS: Ambivalence towards patient self-management and tensions between the
      necessary changes to patients' lifestyles and their culture, makes the GP's role
      difficult and full of conflict. Instead of focusing exclusively on the guidelines
      of diabetes management and provision of information, GPs should explore the
      patients' capabilities of self-management through open communication and accept
      their patients' wishes to protect nutrition as part of their culture.

PMID- 24885604
TI  - CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exocytosis and insulin
      secretion in human and murine pancreatic beta-cells.
AB  - BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene lead to the disease cystic fibrosis (CF). Although patients with CF
      often have disturbances in glucose metabolism including impaired insulin release,
      no previous studies have tested the hypothesis that CFTR has a biological
      function in pancreatic beta-cells. METHODS: Experiments were performed on islets
      and single beta-cells from human donors and NMRI-mice. Detection of CFTR was
      investigated using PCR and confocal microscopy. Effects on insulin secretion were
      measured with radioimmunoassay (RIA). The patch-clamp technique was used to
      measure ion channel currents and calcium-dependent exocytosis (as changes in
      membrane capacitance) on single cells with high temporal resolution. Analysis of
      ultrastructure was done on transmission electron microscopy (TEM) images.
      RESULTS: We detected the presence of CFTR and measured a small CFTR conductance
      in both human and mouse beta-cells. The augmentation of insulin secretion at 16.7
      mM glucose by activation of CFTR by cAMP (forskolin (FSK) or GLP-1) was
      significantly inhibited when CFTR antagonists (GlyH-101 and/or CFTRinh-172) were
      added. Likewise, capacitance measurements demonstrated reduced cAMP-dependent
      exocytosis upon CFTR-inhibition, concomitant with a decreased number of docked
      insulin granules. Finally, our studies demonstrate that CFTR act upstream of the
      chloride channel Anoctamin 1 (ANO1; TMEM16A) in the regulation of cAMP- and
      glucose-stimulated insulin secretion. CONCLUSION: Our work demonstrates a novel
      function for CFTR as a regulator of pancreatic beta-cell insulin secretion and
      exocytosis, and put forward a role for CFTR as regulator of ANO1 and downstream
      priming of insulin granules prior to fusion and release of insulin. The
      pronounced regulatory effect of CFTR on insulin secretion is consistent with
      impaired insulin secretion in patients with CF.

PMID- 24885606
TI  - Association between wheeze and selected air pollution sources in an air pollution
      priority area in South Africa: a cross-sectional study.
AB  - BACKGROUND: An association between wheeze (a symptom of asthma) and environmental
      tobacco smoke (ETS), types of fuel used for residential heating or cooking and
      the frequency of trucks passing near homes, has been reported mainly in developed
      countries. Little is known about the strength of such associations in developing
      countries. This study was conducted in residential areas situated in Ekurhuleni
      Metropolitan Municipality, namely Tembisa and Kempton Park, which form part of
      the Highveld region, a priority area in terms of air pollution in South Africa.
      METHODS: From 3764 eligible school children, aged between 13 and 14 years, from
      16 selected high schools in the study area, 3468 completed a modified
      questionnaire based on the International Study of Asthma and Allergies in
      Childhood (ISAAC). Data were analysed using multiple logistic regression models.
      RESULTS: The results are based on data from 3424 children. In the adjusted
      models, exposure to ETS at school was associated with wheeze ever (OR 1.22 95%
      CI: 1.03 - 1.45) and current wheeze (OR 1.33 95% CI: 1.08 - 1.64). When gas was
      most frequently used for residential heating the likelihood of wheeze ever
      increased by 47% (OR 1.47 95% CI: 1.15 - 1.88). Trucks passing near homes for
      almost the whole day during weekdays, increased the likelihood of wheeze ever (OR
      1.32 95% CI: 1.01 - 1.73), current wheeze (OR 1.61 95% CI: 1.15 - 2.24) and
      current severe wheeze (OR 2.22 95% CI: 1.28 - 3.77). When data were stratified
      according to residential area, for children living in Tembisa, ETS exposure at
      home was associated with current wheeze (OR 1.36 95% CI: 1.06 - 1.77); gas most
      frequently used for residential heating was associated with wheeze ever (OR 1.68
      95% CI: 1.23 - 2.28) and current wheeze (OR 1.61 95% CI: 1.08 - 2.39); paraffin
      most frequently used for residential heating was associated with current severe
      wheeze (OR 1.85 95% CI: 1.04 - 3.28). CONCLUSION: It was concluded that children
      living in one of the air pollution priority areas of South Africa, have an
      increased risk of wheezing due to exposure to both indoor and outdoor air
      pollution sources.

PMID- 24885607
TI  - Effect of acacia honey on cultured rabbit corneal keratocytes.
AB  - BACKGROUND: Acacia honey is a natural product which has proven to have
      therapeutic effects on skin wound healing, but its potential healing effects in
      corneal wound healing have not been studied. This study aimed to explore the
      effects of Acacia honey (AH) on corneal keratocytes morphology, proliferative
      capacity, cell cycle, gene and protein analyses. Keratocytes from the corneal
      stroma of six New Zealand white rabbits were isolated and cultured until passage
      1. The optimal dose of AH in the basal medium (FD) and medium containing serum
      (FDS) for keratocytes proliferation was identified using MTT assay. The
      morphological changes, gene and protein expressions of aldehyde dehydrogenase
      (ALDH), marker for quiescent keratocytes and vimentin, marker for fibroblasts
      were detected using q-RTPCR and immunocytochemistry respectively. Flowcytometry
      was performed to evaluate the cell cycle analysis of corneal keratocytes.
      RESULTS: Cultured keratocytes supplemented with AH showed no morphological
      changes compared to control. Keratocytes cultured in FD and FDS media
      supplemented with 0.025% AH showed optimal proliferative potential compared with
      FD and FDS media, respectively. Gene expressions of ADLH and vimentin were
      increased in keratocytes cultured with AH enriched media. All proteins were
      expressed in keratocytes cultured in all media in accordance to the gene
      expression findings. No chromosomal changes were detected in keratocytes in AH
      enriched media. CONCLUSION: Corneal keratocytes cultured in media supplemented
      with 0.025% AH showed an increase in proliferative capacity while retaining their
      morphology, gene and protein expressions with normal cell cycle. The results of
      the present study show promising role of AH role in accelerating the initial
      stage of corneal wound healing.

PMID- 24885608
TI  - Extraordinary response to crizotinib in a woman with squamous cell lung cancer
      after two courses of failed chemotherapy.
AB  - BACKGROUND: The discovery of the fusion gene echinodermmicro tubule associated
      proteinlike 4-anaplastic lymphoma kinase, EML4-ALK, in patients with non-small
      cell lung cancer has led to the remarkable development of anaplastic lymphoma
      kinase inhibitors, such as crizotinib. Consequently, the clinical outcomes of
      these patients have improved dramatically. Herein, we report the case of a woman
      with ALK gene translocation-squamous cell lung cancer who experienced a
      remarkable tumor response to crizotinib after two courses of failed chemotherapy.
      CASE PRESENTATION: A 55-year-old Chinese woman was diagnosed with cervical lymph
      node metastatic squamous carcinoma. Chest computed tomography scan showed the
      primary tumor in the lower lobe of the right lung. The patient had received two
      successive courses of first-line chemotherapy without tumor response. Tumor cells
      were negative for wild-type of epidermal growth factor receptor/K-RAS variants;
      thus, she was not eligible for tyrosine kinase inhibitor therapy. Unfortunately,
      increased levels of interleukin-6 and carcinoembryonic antigen, and computed
      tomography scan results indicated cancer progression. Once crizotinib was
      approved by the China Food and Drug Administration and the ALK gene translocation
      was identified in tumor cells by fluorescent in situ hybridization, the patient
      commenced treatment with crizotinib. Remarkably, the tumor response to crizotinib
      was classified as partial response after only 26 days of treatment commencement.
      The partial response status has been maintained to date (23 weeks). CONCLUSION:
      Considering this remarkable response to crizotinib, we can safely conclude that
      patients with squamous cell lung cancer should have the option of undergoing ALK
      testing to determine if there is indication for crizotinib treatment even after
      they have failed chemotherapy.

PMID- 24885609
TI  - Informed consent practices for surgical care at university teaching hospitals: a
      case in a low resource setting.
AB  - BACKGROUND: Informed consent in medical practice is essential and a global
      standard that should be sought at all the times doctors interact with patients.
      Its intensity would vary depending on the invasiveness and risks associated with
      the anticipated treatment. To our knowledge there has not been any systematic
      review of consent practices to document best practices and identify areas that
      need improvement in our setting. The objective of the study was to evaluate the
      informed consent practices of surgeons at University teaching Hospitals in a low
      resource setting. METHODS: A cross-sectional study conducted at three university
      teaching hospitals in Uganda. Self-guided questionnaires were left at a central
      location in each of the surgical departments after verbally communicating to the
      surgeons of the intention of the study. Filled questionnaires were returned at
      the same location by the respondents for collection by the research team. In
      addition, 20 in-depth interviews were held with surgeons and a review of 384
      patients' record files for informed consent documentation was done. RESULTS: A
      total of 132 (62.1%) out of 214 questionnaires were completed and returned.
      Respondents were intern doctors, residents and specialists from General surgery,
      Orthopedic surgery, Ear, Nose and Throat, Ophthalmology, Dentistry, Obstetrics
      and Gynaecology departments. The average working experience of respondents was
      4.8 years (SD 4.454, range 0-39 years). 48.8% of the respondents said they
      obtained consent all the time surgery is done while 51.2% did not obtain consent
      all the time. Many of the respondents indicated that informed consent was not
      obtained by the surgeon who operated the patient but was obtained either at
      admission or by nurses in the surgical units. The consent forms used in the
      hospitals were found to be inadequate and many times signed at admission before
      diagnosing the patient's disease. CONCLUSIONS: Informed consent administration
      and documentation for surgical health care is still inadequate at University
      teaching hospitals in Uganda.

PMID- 24885610
TI  - piBUSS: a parallel BEAST/BEAGLE utility for sequence simulation under complex
      evolutionary scenarios.
AB  - BACKGROUND: Simulated nucleotide or amino acid sequences are frequently used to
      assess the performance of phylogenetic reconstruction methods. BEAST, a Bayesian
      statistical framework that focuses on reconstructing time-calibrated molecular
      evolutionary processes, supports a wide array of evolutionary models, but lacked
      matching machinery for simulation of character evolution along phylogenies.
      RESULTS: We present a flexible Monte Carlo simulation tool, called piBUSS, that
      employs the BEAGLE high performance library for phylogenetic computations to
      rapidly generate large sequence alignments under complex evolutionary models.
      piBUSS sports a user-friendly graphical user interface (GUI) that allows
      combining a rich array of models across an arbitrary number of partitions. A
      command-line interface mirrors the options available through the GUI and
      facilitates scripting in large-scale simulation studies. piBUSS may serve as an
      easy-to-use, standard sequence simulation tool, but the available models and data
      types are particularly useful to assess the performance of complex BEAST
      inferences. The connection with BEAST is further strengthened through the use of
      a common extensible markup language (XML), allowing to specify also more advanced
      evolutionary models. To support simulation under the latter, as well as to
      support simulation and analysis in a single run, we also add the piBUSS core
      simulation routine to the list of BEAST XML parsers. CONCLUSIONS: piBUSS offers a
      unique combination of flexibility and ease-of-use for sequence simulation under
      realistic evolutionary scenarios. Through different interfaces, piBUSS supports
      simulation studies ranging from modest endeavors for illustrative purposes to
      complex and large-scale assessments of evolutionary inference procedures.
      Applications are not restricted to the BEAST framework, or even time-measured
      evolutionary histories, and piBUSS can be connected to various other programs
      using standard input and output format.

PMID- 24885611
TI  - The value of (pre)school playgrounds for children's physical activity level: a
      systematic review.
AB  - The (pre)school environment is an important setting to improve children's health.
      Especially, the (pre)school playground provides a major opportunity to intervene.
      This review presents an overview of the existing evidence on the value of both
      school and preschool playgrounds on children's health in terms of physical
      activity, cognitive and social outcomes. In addition, we aimed to identify which
      playground characteristics are the strongest correlates of beneficial effects and
      for which subgroups of children effects are most distinct. In total, 13
      experimental and 17 observational studies have been summarized of which 10 (77%)
      and 16 (94%) demonstrated moderate to high methodological quality, respectively.
      Nearly all experimental studies (n = 11) evaluated intervention effects on time
      spent in different levels of physical activity during recess. Research on the
      effects of (pre)school playgrounds on cognitive and social outcomes is scarce (n
      = 2). The experimental studies generated moderate evidence for an effect of the
      provision of play equipment, inconclusive evidence for an effect of the use of
      playground markings, allocating play space and for multi-component interventions,
      and no evidence for an effect of decreasing playground density, the promotion of
      physical activity by staff and increasing recess duration on children's health.
      In line with this, observational studies showed positive associations between
      play equipment and children's physical activity level. In contrast to
      experimental studies, significant associations were also found between children's
      physical activity and a decreased playground density and increased recess
      duration. To confirm the findings of this review, researchers are advised to
      conduct more experimental studies with a randomized controlled design and to
      incorporate the assessment of implementation strategies and process evaluations
      to reveal which intervention strategies and playground characteristics are most
      effective. 

PMID- 24885612
TI  - Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on
      phenotypic resistance to available non-nucleoside and nucleoside inhibitors in
      China.
AB  - BACKGROUND: The aim of this study was to investigate the role of K101Q, Y181C and
      H221Y emerging in HIV-1 reverse transcriptase with different mutations patterns
      in phenotypic susceptibility to currently available NNRTIs (nevirapine NVP,
      efavirenz EFV) and NRTIs (zidovudine AZT, lamivudine 3TC, stavudine d4T) in
      China. METHODS: Phenotype testing of currently available NNRTIs (NVP, EFV) and
      NRTIs (AZT, 3TC, d4T) was performed on TZM-b1 cells using recombined virus
      strains. P <= 0.05 was defined significant considering the change of 50%
      inhibitory drug concentration (IC50) compared with the reference, while P <= 0.01
      was considered to be statistically significant considering multiple comparisons.
      RESULTS: Triple-mutation K101Q/Y181C/H221Y and double-mutation K101Q/Y181C
      resulted in significant increase in NVP resistance (1253.9-fold and 986.4-fold),
      while only K101Q/Y181C/H221Y brought a 5.00-fold significant increase in EFV
      resistance. Remarkably, K101Q/H221Y was hypersusceptible to EFV (FC = 0.04), but
      was significantly resistant to the three NRTIs. Then, the interaction analysis
      suggested the interaction was not significant to NVP (F = 0.77, P = 0.4061) but
      significant to EFV and other three NRTIs. CONCLUSION: Copresence of mutations
      reported to be associated with NNRTIs confers significant increase to NVP
      resistance. Interestingly, some may increase the susceptibility to EFV.
      Certainly, the double mutation (K101Q/H221Y) also changes the susceptibility of
      viruses to NRTIs. Interaction between two different sites makes resistance more
      complex.

PMID- 24885613
TI  - Activity of Cinnamomum osmophloeum leaf essential oil against Anopheles gambiae
      s.s.
AB  - BACKGROUND: The increasing status of insecticide resistant mosquitoes in sub
      Saharan Africa is a threatening alert to the existing control efforts. All
      sibling species of An. gambiae complex have evolved insecticide resistance in
      wild populations for different approved classes of the insecticides currently in
      use in the field. An alternative compound for vector control is absolutely
      urgently needed. In this study, the larvicidal activity and chemical composition
      of the Cinnamomum osmophloeum leaf essential oils were investigated. METHODS: C.
      osmophloeum leaf essential oils were extracted by hydrodistillation in a
      Clevenger-type apparatus for 6 hours, and their chemical compositions identified
      using GC-MS. These oils were evaluated against An. gambiae s.s. in both
      laboratory and semi-field situations. The WHO test procedures for monitoring
      larvicidal efficacy in malaria vectors were used. RESULTS: The composition of C.
      osmophloeum leaf essential oil has been found to have 11 active compounds. The
      most abundant compound was trans-cinnamaldehyde (70.20%) and the least abundant
      was caryophyllene oxide (0.08%). The larvicidal activity was found to be dosage
      and time dependant both in laboratory and semi-field environments with mortality
      ranging from 0% to 100%. The LC50 value was found to vary from 22.18 to 58.15
      MUg/ml in the laboratory while in semi-field environments it was 11.91 to 63.63
      MUg/ml. The LC90 value was found to range between 57.71 to 91.54 MUg/ml in the
      laboratory while in semi-field environments was 52.07 to 173.77 MUg/ml. Mortality
      ranged from 13% to 100% in the laboratory while in semi-field environments it
      ranged between 43% to 100% within mortality recording time intervals of 12, 24,
      48, and 72 hours. CONCLUSIONS: The larvicidal activity shown by C. osmophloeum
      leaf essential oil is a promising alternative to existing larvicides or to be
      incorporated in integrated larval source management compounds for An. gambiae s.s
      control. The efficacy observed in this study is attributed to both major and
      minor compounds of the essential oils.

PMID- 24885614
TI  - Efficacy and complication of endoscopic submucosal dissection for superficial
      esophageal carcinoma: a systematic review and meta-analysis.
AB  - AIM: For patients with superficial esophageal carcinoma, ESD was one of treatment
      modalities to remove the lesion safely and effectively. We perform this meta
      analysis to determine the efficacy and incidence of complication of ESD for
      patients with superficial esophageal carcinoma. METHOD: Articles were searched in
      MEDLINE (PubMed and Ovid), Cochrane Database of Systemic Reviews, Google scholar,
      and Web of Science. Two reviewers independently searched and extracted data. Meta
      analysis of the efficacy of ESD was analyzed by calculating pooled en bloc and R0
      resection rate. Incidence of complications such as perforation, stenosis and
      mediastinal emphysema was also calculated. Pooling was conducted using either
      fixed-effects model or random-effects model depending on the heterogeneity across
      studies. RESULTS: 21 studies (1152 patients and 1240 lesions) were included in
      this analysis. The pooled en bloc resection rate was 99% (95% CI 99%-100%).
      Stratified by tumor size, en bloc resection rates did not show any significant
      difference. The pooled R0 resection rate was 90% (95% CI 87%-93%). The pooled R0
      resection rate was 85% (95% CI, 80%-90%) for large tumor and 92% (95% CI, 87%
      93%) for small tumor (p < 0.001). Stenosis served as the most common reported
      complication with pooled incidence of 5% (95% CI 3-8%), followed by perforation
      (1%, 95% CI 0-1%) and mediastinal emphysema (0% CI 0-1%). The incidence of
      postoperative stenosis decreased significantly after 2011 (2%, 95% CI 0-3%)
      compared with that before 2011 (9%, 95% CI 3-8%) (p < 0.001). CONCLUSION: ESD was
      an efficient modality for treating superficial esophageal carcinoma, with perfect
      en bloc and R0 resection rate and low complication rate. The most common
      complication of ESD was stenosis. Although recurrence rate was low, patients
      should be maintained in a scheduled surveillance program.

PMID- 24885615
TI  - Genome-wide identification of Hfq-regulated small RNAs in the fire blight
      pathogen Erwinia amylovora discovered small RNAs with virulence regulatory
      function.
AB  - BACKGROUND: Erwinia amylovora is a phytopathogenic bacterium and causal agent of
      fire blight disease in apples and pears. Although many virulence factors have
      been characterized, the coordination of expression of these virulence factors in
      E. amylovora is still not clear. Regulatory small RNAs (sRNAs) are important post
      transcriptional regulatory components in bacteria. A large number of sRNAs
      require the RNA chaperone Hfq for both stability and functional activation. In E.
      amylovora, Hfq was identified as a major regulator of virulence and various
      virulence traits. However, information is still lacking about Hfq-dependent sRNAs
      on a genome scale, including the virulence regulatory functions of these sRNAs in
      E. amylovora. RESULTS: Using both an RNA-seq analysis and a Rho-independent
      terminator search, 40 candidate Hfq-dependent sRNAs were identified in E.
      amylovora. The expression and sizes of 12 sRNAs and the sequence boundaries of
      seven sRNAs were confirmed by Northern blot and 5' RACE assay respectively.
      Sequence conservation analysis identified sRNAs conserved only in the Erwinia
      genus as well as E. amylovora species-specific sRNAs. In addition, a dynamic re
      patterning of expression of Hfq-dependent sRNAs was observed at 6 and 12 hours
      after induction in Hrp-inducing minimal medium. Furthermore, sRNAs that control
      virulence traits were characterized, among which ArcZ positively controls the
      type III secretion system (T3SS), amylovoran exopolysaccahride production,
      biofilm formation, and motility, and negatively modulates attachment while RmaA
      (Hrs6) and OmrAB both negatively regulate amylovoran production and positively
      regulate motility. CONCLUSIONS: This study has significantly enhanced our
      understanding of the Hfq-dependent sRNAs in E. amylovora at the genome level. The
      identification of multiple virulence-regulating sRNAs also suggests that post
      transcriptional regulation by sRNAs may play a role in the deployment of
      virulence factors needed during varying stages of pathogenesis during host
      invasion by E. amylovora.

PMID- 24885616
TI  - Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus
      patients: a systemic review and meta-analysis.
AB  - BACKGROUND: Insulin is widely used in patients with type 2 diabetes mellitus
      (T2DM). More attention was focused on its higher risk of colorectal cancer (CRC).
      This meta-analysis examined the relationship between levels of insulin use and
      the risk of CRC. METHODS: A meta-analysis using data from 12 published
      epidemiologic studies (7 case-control, and 5 cohort studies) published before
      Jan. 2014 was done to examine the association between insulin use and CRC. Random
      effects analyses were done to calculate relative risk (RR) and 95% confidence
      intervals (CI). Heterogeneity among studies was measured by the chi2 and I2
      statistic. RESULTS: Overall, the risk of CRC was significantly associated with
      insulin use to a random-effects model (RR, 1.69; 95% CI, 1.25 -2.27). When
      subgroup analyses were conducted according to the study types, no associations
      were detected in cohort group (RR, 1.25; 95% CI, 0.95-1.65; I2, 75.7%); however
      significant association was detected in case-control group (RR, 2.15; 95% CI,
      1.41-3.26; I2, 89.1%). CONCLUSIONS: A significant harmful effect of insulin,
      observed mainly among case-control studies, may result from study design
      differences and amount of included studies. Although these results suggest a
      harmful effect of insulin use for CRC risk, additional large studies are
      warranted to support these preliminary evidences. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2194715731194123.

PMID- 24885617
TI  - Impact of housing improvement and the socio-physical environment on the mental
      health of children's carers: a cohort study in Australian Aboriginal communities.
AB  - BACKGROUND: The mental health of carers is an important proximate factor in the
      causal web linking housing conditions to child health, as well as being important
      in its own right. Improved understanding of the nature of the relationships
      between housing conditions, carer mental health and child health outcomes is
      therefore important for informing the development of housing programs. This paper
      examines the relationship between the mental health of the carers of young
      children, housing conditions, and other key factors in the socio-physical
      environment. METHODS: This analysis is part of a broader prospective cohort study
      of children living in Aboriginal communities in the Northern Territory (NT) of
      Australia at the time of major new community housing programs. Carer's mental
      health was assessed using two validated scales: the Affect Balance scale and the
      Brief Screen for Depression. The quality of housing infrastructure was assessed
      through detailed surveys. Secondary explanatory variables included a range of
      socio-environmental factors, including validated measures of stressful life
      events. Hierarchical regression modelling was used to assess associations between
      outcome and explanatory variables at baseline, and associations between change in
      housing conditions and change in outcomes between baseline and follow-up.
      RESULTS: There was no clear or consistent evidence of a causal relationship
      between the functional state of household infrastructure and the mental health of
      carers of young children. The strongest and most consistent associations with
      carer mental health were the measures of negative life events, with a dose
      response relationship, and adjusted odds ratio of over 6 for carers in the
      highest stress exposure category at baseline, and consistent associations in the
      follow up analysis. CONCLUSIONS: The findings highlight the need for housing
      programs to be supported by social, behavioral and community-wide environmental
      programs if potential health gains are to be more fully realized, and for
      rigorous evaluation of such programs for the purpose of informing future housing
      initiatives.

PMID- 24885619
TI  - The influence of locus of control on self-rated health in context of chronic
      disease: a structural equation modeling approach in a cross sectional study.
AB  - BACKGROUND: Self-rated health is a robust predictor of several health outcomes,
      such as functional ability, health care utilization, morbidity and mortality. The
      purpose of this study is to investigate and explore how health locus of control
      and disease burden relate to self-rated health among patients at risk for
      cardiovascular disease. METHODS: In 2009, 414 Swedish patients who were using
      statins completed a questionnaire about their health, diseases and their views on
      the three-dimensional health locus of control scale. The scale determines which
      category of health locus of control - internal, chance or powerful others - a
      patient most identifies with. The data was analyzed using logistic regression and
      a structural equation modeling approach. RESULTS: The analyses showed positive
      associations between internal health locus of control and self-rated health, and
      a negative association between health locus of control in chance and powerful
      others and self-rated health. High internal health locus of control was
      negatively associated with the cumulative burden of diseases, while health locus
      of control in chance and powerful others were positively associated with burden
      of diseases. In addition, age and education level had indirect associations with
      self-rated health through health locus of control. CONCLUSIONS: This study
      suggests that self-rated health is positively correlated with internal locus of
      control and negatively associated with high locus of control in chance and
      powerful others in patients at high risk for cardiovascular disease. Furthermore,
      disease burden seems to be negatively associated with self-rated health.

PMID- 24885621
TI  - Designing and implementing interventions to change clinicians' practice in the
      management of uncomplicated malaria: lessons from Cameroon.
AB  - BACKGROUND: Effective case management of uncomplicated malaria is a fundamental
      pillar of malaria control. Little is known about the various steps in designing
      interventions to accompany the roll out of rapid diagnostic tests (RDTs) and
      artemisinin-based combination therapy (ACT). This study documents the process of
      designing and implementing interventions to change clinicians' practice in the
      management of uncomplicated malaria. METHODS: A literature review combined with
      formative quantitative and qualitative research were carried out to determine
      patterns of malaria diagnosis and treatment and to understand how malaria and its
      treatment are enacted by clinicians. These findings were used, alongside a
      comprehensive review of previous interventions, to identify possible strategies
      for changing the behaviour of clinicians when diagnosing and treating
      uncomplicated malaria. These strategies were discussed with ministry of health
      representatives and other stakeholders. Two intervention packages - a basic and
      an enhanced training were outlined, together with logic model to show how each
      was hypothesized to increase testing for malaria, improve adherence to test
      results and increase appropriate use of ACT. The basic training targeted
      clinicians' knowledge of malaria diagnosis, rapid diagnostic testing and malaria
      treatment. The enhanced training included additional modules on adapting to
      change, professionalism and communicating effectively. Modules were delivered
      using small-group work, card games, drama and role play. Interventions were
      piloted, adapted and trainers were trained before final implementation. RESULTS:
      Ninety-six clinicians from 37 health facilities in Bamenda and Yaounde sites
      attended either 1-day basic or 3-day enhanced training. The trained clinicians
      then trained 632 of their peers at their health facilities. Evaluation of the
      training revealed that 68% of participants receiving the basic and 92% of those
      receiving the enhanced training strongly agreed that it is not appropriate to
      prescribe anti-malarials to a patient if they have a negative RDT result.
      CONCLUSION: Formative research was an important first step, and it was valuable
      to engage stakeholders early in the process. A logic model and literature reviews
      were useful to identify key elements and mechanisms for behaviour change
      intervention. An iterative process with feedback loops allowed appropriate
      development and implementation of the intervention. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01350752.

PMID- 24885620
TI  - Associations between different types of physical activity and teachers' perceived
      mental, physical, and work-related health.
AB  - BACKGROUND: The teaching profession is characterized by high levels of stress and
      physical complaints, which might be improved through regular participation in
      physical activity (PA). However, the effect of PA on mental and physical health
      is not always consistent and depends on the type of PA performed. The aim of this
      study was to examine the mental, physical, and work-related health of Flemish
      secondary school teachers and identify the impact on those health variables by
      demographic and teaching-related factors and various types of PA. METHODS: This
      study included an online survey conducted across a representative sample of
      secondary school teachers (n = 1066, average age 40 years; 68 percent female).
      Level of PA and sitting time were estimated using the International Physical
      Activity Questionnaire, and perceived mental health and physical health were
      estimated using the Short Form 36. Work-related factors such as job satisfaction,
      occupational stress, and absenteeism were also collected. T-tests, ANOVAs, and
      linear regression analyses were performed. RESULTS: Flemish secondary school
      teachers have poorer perceived mental and physical health than a general healthy
      population. This difference is particularly evident among female teachers, who
      reported lower perceived health, more occupational stress, and more absent days
      compared to their male colleagues. Higher participation in leisure-time PA was
      associated with a more positive perceived health. In contrast, higher levels of
      occupational PA and sitting time had a negative impact on perceived health. Total
      amount of PA, total amount of moderate-to-vigorous PA, transportation-related PA,
      and PA at home were not associated to teachers' perceived health. CONCLUSION:
      Because secondary school teachers' levels of perceived health are low, they are
      an important target group for interventions aiming to improve health. Only
      leisure-time PA was associated with more positive perceived health. This finding
      may indicate that teachers performing more exercise during leisure time, or in a
      more autonomous way, may be more resistant to physical and mental health
      problems. Future research should verify whether promoting leisure-time PA among
      teachers has the potential to improve their mental and physical health, and
      counteract the negative associations between teachers' health and their
      occupational PA.

PMID- 24885622
TI  - Influence of nutrition on infection and re-infection with soil-transmitted
      helminths: a systematic review.
AB  - BACKGROUND: The relationship between nutrition and soil-transmitted helminthiasis
      is complex and warrants further investigation. We conducted a systematic review
      examining the influence of nutrition on infection and re-infection with soil
      transmitted helminths (i.e. Ascaris lumbricoides, hookworm, Trichuris trichiura
      and Strongyloides stercoralis) in humans. Emphasis was placed on the use of
      nutritional supplementation, alongside anthelminthic treatment, to prevent re
      infection with soil-transmitted helminths. METHODS: We searched eight electronic
      databases from inception to 31 July 2013, with no restriction of language or type
      of publication. For studies that met our inclusion criteria, we extracted
      information on the soil-transmitted helminth species, nutritional supplementation
      and anthelminthic treatment. Outcomes were presented in forest plots and a
      summary of findings (SoF) table. An evidence profile (EP) was generated by rating
      the evidence quality of the identified studies according to the GRADE system.
      RESULTS: Fifteen studies met our inclusion criteria; eight randomised controlled
      trials and seven prospective cohort studies. Data on A. lumbricoides were
      available from all studies, whereas seven and six studies additionally contained
      data on T. trichiura and hookworm, respectively. None of the studies contained
      data on S. stercoralis. Positive effects of nutritional supplementation or the
      host's natural nutritional status on (re-)infection with soil-transmitted
      helminths were reported in 14 studies, while negative effects were documented in
      six studies. In terms of quality, a high, low and very low quality rating was
      assigned to the evidence from four, six and five studies, respectively.
      CONCLUSIONS: Our findings suggest that the current evidence-base is weak,
      precluding guidelines on nutrition management as a potential supplementary tool
      to preventive chemotherapy targeting soil-transmitted helminthiasis. Moreover,
      several epidemiological, immunological and methodological issues have been
      identified, and these should be considered when designing future studies.

PMID- 24885623
TI  - Chronic Bickerstaff's encephalitis with cognitive impairment, a reality?
AB  - BACKGROUND: Bickerstaff's encephalitis (BE) is an acute post-infectious
      demyelinating disease with albuminocytological dissociation. A chronic form has
      rarely been described previously. CASE PRESENTATION: A 44-year-old man was
      hospitalized for drowsiness, cognitive complaint limb weakness, ataxia and
      sensory disturbance after diarrhea. Neuropsychological evaluation showed slowing,
      memory and executive function impairment, while analysis of the CSF showed
      albuminocytological dissociation. Immunologic tests showed positive anti
      ganglioside antibodies (anti-GM1 IgM, anti-GD1a IgG and anti-GD1b IgM). Brain MRI
      was normal but SPECT showed bilateral temporal and frontal hypoperfusion. Outcome
      under immunoglobulin treatment (IVIG) was favorable with an initial improvement
      but was marked by worsening after a few weeks. Consequently, the patient was
      treated with IVIG every 2 months due to the recurrence of symptoms after 6 weeks.
      CONCLUSION: This case raises the question of the existence of a chronic form of
      BE with cognitive impairment, in the same way as chronic inflammatory
      demyelinating polyneuropathy is considered to be a chronic form of Guillain-Barre
      syndrome.

PMID- 24885624
TI  - Prognostic factors for survival and radiation necrosis after stereotactic
      radiosurgery alone or in combination with whole brain radiation therapy for 1-3
      cerebral metastases.
AB  - BACKGROUND: In the present study factors affecting survival and toxicity in
      cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were
      analyzed with special focus on radiation necrosis. PATIENTS AND METHODS: 340
      patients with 1-3 cerebral metastases having been treated with SRS were
      retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET
      imaging. Univariate and multivariate analysis using a Cox proportional hazards
      regression model and log-rank test were performed to determine the prognostic
      value of treatment-related and individual factors for outcome and SRS-related
      complications. RESULTS: Median overall survival was 282 days and median follow-up
      721 days. 44% of patients received WBRT during the course of disease. Concerning
      univariate analysis a significant difference in overall survival was found for
      Karnofsky Performance Status (KPS <= 70: 122 days; KPS > 70: 342 days), for RPA
      (recursive partitioning analysis) class (RPA class I: 1800 days; RPA class II:
      281 days; RPA class III: 130 days), irradiated volume (<=2.5 ml: 354 days; > 2.5
      ml: 234 days), prescribed dose (<=18 Gy: 235 days; > 18 Gy: 351 days), gender
      (male: 235 days; female: 327 days) and whole brain radiotherapy (+WBRT: 341 days/
      WBRT: 231 days). In multivariate analysis significance was confirmed for KPS, RPA
      class and gender. MRI and clinical symptoms suggested radiation necrosis in 21
      patients after SRS +/- whole brain radiotherapy (WBRT). In five patients
      clinically relevant radiation necrosis was confirmed by PET imaging. CONCLUSIONS:
      SRS alone or in combination with WBRT represents a feasible option as initial
      treatment for patients with brain metastases; however a significant subset of
      patients may develop neurological complications. Performance status, RPA class
      and gender were identified to predict improved survival in cerebral metastasized
      patients.

PMID- 24885625
TI  - High glucose increases LPS-induced DC apoptosis through modulation of ERK1/2, AKT
      and Bax/Bcl-2.
AB  - BACKGROUND: This study investigates the effect of glucose on the LPS-induced
      apoptosis of dendritic cells in the intestinal tract of mice and the dendritic
      cell line DC2.4. METHODS: Flow cytometry was used to detect dendritic cell
      apoptosis both in vivo and in vitro. Hoechst 33258 staining was used to detect
      the morphological changes characteristic of apoptotic nuclei. Expression of
      apoptosis related proteins was investigated by western blot analysis and
      immunohistochemistry. RESULTS: Pretreatment with a high concentration of glucose
      increased apoptosis of LPS-treated dendritic cells both in vivo and in vitro at
      24 h. No effect was evident at the earlier time points of 15 min and 6 h in
      vitro. Furthermore, at 24 hours the expression of the survival proteins AKT, ERK
      and Bcl-2 was decreased, while the expression of the proapoptotic protein Bax was
      increased. AKT, ERK, Bcl-2 and Bax were mainly located in the cytoplasm by
      immunohistochemistry. CONCLUSIONS: These results suggest that high glucose
      concentrations might prime dendritic cells for apoptosis induced by LPS in the
      intestinal tract through upregulating the expression of Bax and downregulating
      the expression of AKT, ERK and Bcl-2. Therefore, this study may give clues to
      understanding the immunological mechanism behind gastrointestinal complications
      in diabetes mellitus.

PMID- 24885627
TI  - Thyrotropin levels within the lower normal range are associated with an increased
      risk of hip fractures in euthyroid women, but not men, over the age of 65 years.
AB  - CONTEXT: The contemporary literature on the relationship between serum TSH levels
      and osteoporotic fractures in euthyroid individuals is limited by conflicting
      results and analyses conducted on a small number of fractures. OBJECTIVE: Our
      objective was to examine the association between the normal range of variation of
      TSH and the incidence of hip fractures in male and female euthyroid patients aged
      65 years or older. DESIGN AND SETTING: We performed a population-based historical
      prospective cohort study within the Clalit Health Services population.
      PARTICIPANTS: Clalit Health Services members aged >=65 years with at least 1 TSH
      measurement during the year 2004. We excluded patients with preexisting hip
      fracture, thyroid disease, malignancy, or chronic kidney disease. OUTCOME
      MEASURES: The primary outcome was hip fracture, and the secondary outcome was any
      other osteoporotic fracture. STATISTICAL ANALYSIS: Adjusted odds ratios comparing
      episodes of each outcome across 3 TSH groups (low, 0.35-1.6 mIU/L; intermediate,
      1.7-2.9 mIU/L; high, 3-4.2 mIU/L) were generated using logistic regression
      models. RESULTS: The 14 325 included participants suffered from 514 hip fractures
      (mean follow-up, 102 +/- 3 months). Women, but not men, in the lowest TSH group
      had a higher incidence of hip fractures (odds ratio = 1.28, 95% confidence
      interval = 1.03-1.59, P = .029) when compared with the intermediate group, after
      multivariate adjustment for age, comorbidities, and use of drugs affecting bone
      metabolism. There was no difference in hip fracture incidence between
      intermediate- and high-TSH groups. No association was found between TSH levels
      and other osteoporotic fractures. CONCLUSIONS: TSH levels within the lower normal
      range are associated with an increased risk of hip fractures in euthyroid women,
      but not men, aged 65 years and more.

PMID- 24885626
TI  - miR-300 inhibits epithelial to mesenchymal transition and metastasis by targeting
      Twist in human epithelial cancer.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a key step of the
      progression of tumor cell metastasis. Recent work has demonstrated some miRNAs
      play critical roles in EMT. In this study, we focused on the roles of miR-300 in
      regulating EMT. METHODS: The expression levels of miR-300 were examined in
      epithelial carcinoma cells that underwent an EMT using quantitative reverse
      transcription-PCR. The role of miR-300 in EMT was investigated by transfection of
      the miR-300 mimic or inhibitor in natural epithelial-mesenchymal phenotype cell
      line pairs and in transforming growth factor (TGF) beta-induced EMT cell models.
      A luciferase reporter assay and a rescue experiment were conducted to confirm the
      target gene of miR-300. The efficacy of miR-300 against tumor invasion and
      metastasis was evaluated both in vitro and in vivo. Correlation analysis between
      miR-300 expression and the expression levels of its target gene, as well as tumor
      metastasis was performed in specimens from patients with head and neck squamous
      cell carcinoma (HNSCC). RESULTS: MiR-300 was found down-regulated in the HNSCC
      cells and breast cancer cells that underwent EMT. Ectopic expression of miR-300
      effectively blocked TGF-beta-induced EMT and reversed the phenotype of EMT in HN
      12 and MDA-MB-231 cells, but inhibition of miR-300 in the epithelial phenotype
      cells, HN-4 and MCF-7 cells, could induce EMT. The luciferase reporter assay and
      the rescue assay results showed that miR-300 directly targets the 3'UTR of Twist.
      Enforced miR-300 expression suppressed cell invasion in vitro and experimental
      metastasis in vivo. Clinically, miR-300 expression was found inversely correlated
      with Twist expression and reduced miR-300 was associated with metastasis in
      patient specimens. CONCLUSIONS: Down-regulation of miR-300 is required for EMT
      initiation and maintenance. MiR-300 may negatively regulate EMT by direct
      targeting Twist and therefore inhibit cancer cell invasion and metastasis, which
      implicates miR-300 as an attractive candidate for cancer therapy.

PMID- 24885628
TI  - Associations of serum 25-hydroxyvitamin D concentrations with quality of life and
      self-rated health in an older population.
AB  - CONTEXT: Vitamin D deficiency has been associated with impaired physical
      functioning, depression, and several chronic diseases and might thereby affect
      quality of life and self-rated health. OBJECTIVE: The aim of this study was to
      assess relationships of serum 25-hydroxyvitamin D [25(OH)D] with quality of life
      and self-rated health and to examine whether physical performance, depressive
      symptoms, and number of chronic diseases mediate these relationships. DESIGN: We
      analyzed data from the Longitudinal Aging Study Amsterdam, an ongoing population
      based cohort study of older Dutch individuals. MAIN OUTCOME MEASURES: Serum
      25(OH)D was classified into the following categories: less than 25, 25-50, and 50
      nmol/L or greater. We assessed quality of life (QOL) using the Short Form-12
      Health Survey (SF-12; n = 862) and self-rated health (SRH) with a single
      question, dichotomized into good vs poor SRH (n = 1248). RESULTS: Individuals
      with serum 25(OH)D less than 25 nmol/L scored lower on the physical component
      score of the SF-12 and had a lower odds on good SRH score compared with
      individuals with serum 25(OH)D greater than 50 nmol/L (beta (95% confidence
      interval) -3.9 (-6.5 to -1.3) for SF-12, and odds ratio [95% confidence interval)
      0.50 (0.33-0.76) for SRH]. Physical performance, depressive symptoms, and the
      number of chronic diseases were associated with vitamin D status, QOL, and SRH.
      Adding all these potential mediators to regression models attenuated associations
      of 25(OH)D less than 25 nmol/L with QOL with 78% and SRH with 32%. CONCLUSION:
      Lower 25(OH)D status is related to lower scores on QOL and SRH. A large part of
      the association with QOL can statistically be explained by physical performance,
      depressive symptoms, and the number of chronic diseases.

PMID- 24885629
TI  - Measurements of 25-hydroxyvitamin D concentrations in archived dried blood spots
      are reliable and accurately reflect those in plasma.
AB  - CONTEXT: Recognition that vitamin D might be associated with many chronic
      diseases has led to large-scale epidemiological and clinical studies. Dried blood
      spots (DBS) are a useful resource for these studies. Consequently, accurate,
      efficient, and inexpensive assays to quantify 25-hydroxyvitamin D (25OHD) in DBS
      are required. OBJECTIVE: This study evaluated the validity and reliability of a
      liquid chromatography-tandem mass spectrometry assay for measuring 25OHD in
      archived DBS and compared measurements of 25OHD in DBS with those in plasma.
      DESIGN AND PARTICIPANTS: Sixty-two participants in the Melbourne Collaborative
      Cohort Study who had plasma and matching DBS stored since study entry in the
      early 1990s were randomly selected for a study calibrating 25OHD concentrations
      in DBS with plasma. As part of a study of vitamin D and mortality, cancer, and
      diabetes, we also assessed the reliability of measurements from DBS using 500
      replicates placed randomly within 31 batches run over 15 months. OUTCOME MEASURE:
      25OHD concentrations were measured by liquid chromatography-tandem mass
      spectrometry. RESULTS: There was good agreement between measurements of 25OHD
      from DBS and plasma; R(2) = 0.73 from a regression of plasma concentration on DBS
      concentration. The within-batch and between-batch intraclass correlations from
      the 500 replicate measurements were 0.82 (95% confidence interval, 0.80, 0.85)
      and 0.73 (95% confidence interval, 0.68, 0.78), respectively. CONCLUSIONS:
      Measuring 25OHD in DBS is a valid and reliable alternative to measuring 25OHD in
      sera or plasma. A simple calibration model was developed to convert measurements
      from DBS to equivalent plasma measurements, thus enabling comparisons against
      clinical reference ranges and with studies using sera or plasma samples.

PMID- 24885630
TI  - A mutated vitamin D receptor in hereditary vitamin D-resistant rickets prevents
      induction of bronchial hyperreactivity and inflammation.
AB  - CONTEXT: Previous studies have reported an association between vitamin D
      deficiency and asthma. Hereditary 1,25-dihydroxyvitamin D-resistant rickets
      (HVDRR) patients provide a natural model to assess the role of the vitamin D
      receptor (VDR) in regulating human lung immune responses and airway
      hyperreactivity. OBJECTIVES: The aim of the study was to determine the role of
      the VDR on lung functions, airways, and systemic markers of inflammation and
      allergy in HVDRR patients. DESIGN AND METHODS: Thirteen HVDRR patients (aged 6-37
      y) and 17 normal controls (aged 6-38 y) underwent spirometry, a methacholine
      challenge test (MCT), blood tests, allergy skin tests, determination of
      fractional exhaled nitric oxide, and measurement of serum and exhaled breath
      condensate cytokines, including IL-4, IL-5, IL-10, IL-17, and interferon-gamma
      levels. RESULTS: All HVDRR patients had negative MCT results, whereas six
      controls (35.3%) had positive MCT results (P < .014). Serum IgE levels,
      eosinophil counts, and fractional exhaled nitric oxide and allergy skin test
      results were similar for the HVDRR patients and controls, as were the serum
      cytokine concentrations. The HVDRR patients had different cytokine levels in
      their exhaled breath condensate (increased IL-4 and IL-17 and decreased IL-5, IL
      10, and interferon-gamma levels) compared to the controls (P < .005).
      CONCLUSIONS: HVDRR patients show diverse exhaled cytokine profiles but seem to be
      protected against provoked bronchial hyperreactivity and clinical asthma. These
      findings suggest that an intact VDR has an important role in asthma
      pathophysiology.

PMID- 24885631
TI  - 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP
      concentration and genotype.
AB  - CONTEXT: There is uncertainty over the equivalence of vitamins D2 and D3 to
      maintain plasma 25-hydroxyvitamin D (25(OH)D). OBJECTIVE: The objective of the
      study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two
      distinct populations with different dietary calcium intake and 25(OH)D status.
      PARTICIPANTS: Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or
      the United Kingdom (n = 18) participated in the study. INTERVENTIONS: The
      intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated
      25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days. MAIN OUTCOME
      MEASURES: 25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and
      vitamin D binding protein (DBP) and DBP genotypes were measured. RESULTS:
      25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life
      [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs
      14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6
      (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P <
      .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The
      Gambia and United Kingdom, respectively. Half-lives were positively associated
      with plasma DBP concentration for countries combined [25(OH)D2 half-life:
      regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half
      life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d;
      P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants.
      The DBP concentration * country interactions were not significant. DBP Gc1f/1f
      homozygotes had shorter 25(OH)D2 half-lives compared with other combined
      genotypes (P = .007) after correction for country. CONCLUSIONS: 25(OH)D2 half
      life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP
      concentration and genotype. The stable isotope 25(OH)D half-life measurements
      provide a novel tool to investigate vitamin D metabolism and vitamin D
      expenditure and aid in the assessment of vitamin D requirements.

PMID- 24885632
TI  - Soluble Flt1 and placental growth factor are novel determinants of newborn
      thyroid (dys)function: the generation R study.
AB  - CONTEXT: Adequate thyroid hormone availability during fetal and early life is
      crucial for normal child growth and development. Fetal growth heavily depends on
      angiogenesis. Placental growth factor (PlGF) is a proangiogenic factor sharing
      high homology with vascular endothelial growth factor, whereas soluble FMS-like
      tyrosine kinase-1 (sFlt1) is a potent antagonist of vascular endothelial growth
      factor and PlGF signaling. Because the thyroid is a highly vascularized organ, we
      hypothesized that fetal angiogenic factors influence in utero thyrogenesis and
      impair newborn thyroid function. Therefore, we investigated the association
      between sFlt1 and PlGF on newborn thyroid function. DESIGN, SETTING, AND
      PARTICIPANTS: sFlt1, PlGF, TSH, and free T4 (FT4) were determined in cord serum
      of 3525 newborns from a large prospective cohort study. Analyses were adjusted
      for relevant maternal and child covariates. RESULTS: sFlt1 levels were positively
      associated with TSH (beta 0.07 +/- 0.02 mU/L; P < .001) and inversely with FT4
      (beta -0.58 +/- 0.11; P < .001). PlGF showed a positive association with FT4
      (beta 0.19 +/- 0.02; P < .001). Elevated levels of sFlt1 were associated with a
      2.8-fold increased risk of hypothyroxinemia (P = .04). Decreased levels of PlGF
      were associated with a 6.7-fold increased risk of hypothyroxinemia (P < .001).
      Within the normal range, a dose-dependent effect of sFlt1 on thyroid dysfunction
      was observed: high-normal sFlt1 levels were associated with a 17.7-fold increased
      risk of hypothyroxinemia (P < .001) and a 2.7-fold increased risk of
      hyperthyrotropinemia (P = .01). CONCLUSION: Fetal angiogenic factors sFlt1 and
      PlGF are associated with newborn thyroid function. Possible effects are most
      likely mediated through effects on in utero thyrogenesis. Abnormal as well as
      normal-range fetal sFlt1 and PlGF levels influence the risk of impaired newborn
      thyroid function, which has been associated with adverse neurodevelopmental
      effects. These data provide important novel insights into the physiology of
      thyrogenesis and into the etiology of newborn thyroid (dys)function.

PMID- 24885633
TI  - Secretions from the ventral eversible gland of Spodoptera exigua caterpillars
      activate defense-related genes and induce emission of volatile organic compounds
      in tomato, Solanum lycopersicum.
AB  - BACKGROUND: Plant induced defense against herbivory are generally associated with
      metabolic costs that result in the allocation of photosynthates from growth and
      reproduction to the synthesis of defense compounds. Therefore, it is essential
      that plants are capable of sensing and differentiating mechanical injury from
      herbivore injury. Studies have shown that oral secretions (OS) from caterpillars
      contain elicitors of induced plant responses. However, studies that shows whether
      these elicitors originated from salivary glands or from other organs associated
      with feeding, such as the ventral eversible gland (VEG) are limited. Here, we
      tested the hypothesis that the secretions from the VEG gland of Spodoptera exigua
      caterpillars contain elicitors that induce plant defenses by regulating the
      expression of genes involved in the biosynthesis of volatile organic compounds
      (VOCs) and other defense-related genes. To test this hypothesis, we quantified
      and compared the activity of defense-related enzymes, transcript levels of
      defense-related genes and VOC emission in tomato plants damaged by S. exigua
      caterpillars with the VEG intact (VEGI) versus plants damaged by caterpillars
      with the VEG ablated (VEGA). RESULTS: The quantified defense-related enzymes
      (i.e. peroxidase, polyphenol oxidase, and lipoxigenase) were expressed in
      significantly higher amounts in plants damaged by VEGI caterpillars than in
      plants damaged by VEGA caterpillars. Similarly, the genes that encode for the key
      enzymes involved in the biosynthesis of jasmonic acid and terpene synthase genes
      that regulate production of terpene VOCs, were up-regulated in plants damaged by
      VEGI caterpillars. Moreover, the OS of VEGA caterpillars were less active in
      inducing the expression of defense genes in tomato plants. Increased emissions of
      VOCs were detected in the headspace of plants damaged by VEGI caterpillars
      compared to plants damaged by VEGA caterpillars. CONCLUSION: These results
      suggest that the VEG of S. exigua caterpillars contains elicitors of late plant
      defense signaling in tomato which trigger defense-related enzymatic activity,
      regulate expression of defense-related genes, and induce emission of plant VOCs.
      These signaling cascades may have important ramifications for plant-insect and
      tritrophic interactions.

PMID- 24885634
TI  - Fluorination of flavones and chromones using elemental fluorine.
AB  - Flavonoids are abundant micronutrients in our diet, possessing various biological
      activities. Fluorine was successfully added across the double bond of various
      flavones and chromones. The difluoro derivative products were easily
      dehydrofluorinated to form the corresponding 3-fluoroflavones and 3
      fluorochromones. 

PMID- 24885635
TI  - MicroRNA profiling of rats with ochratoxin A nephrotoxicity.
AB  - BACKGROUND: Nephrotoxicity is the most prominent one among the various toxicities
      of ochratoxin A (OTA). MicroRNAs (miRNAs) are small non-coding RNAs that have an
      impact on a wide range of biological processes by regulating gene expression at
      post-transcriptional level or protein systhesis level. The objective of this
      study is to analyze miRNA profiling in the kidneys of rats gavaged with OTA.
      RESULTS: To profile miRNAs in the kidneys of rats with OTA nephrotoxicity, high
      throughput sequencing and bioinformatics approaches were applied to analyze the
      miRNAs in the kidney of rats following OTA treatment. A total of 409 known miRNAs
      and 8 novel miRNAs were identified in the kidney and the levels of the novel
      miRNAs were varied in response to different doses of OTA. Expression of miR-129,
      miR-130a, miR-130b, miR-141, miR-218b and miR-3588 were uniquely suppressed in
      mid dose but then elevated in high dose, with opposite expression to their target
      genes. The expression pattern was closely related with the "MAPK signaling
      pathway". Dicer1 and Drosha were significantly suppressed, indicating an
      impairment of miRNA biogenesis in response to OTA. CONCLUSIONS: The abrogation of
      miRNA maturation process suggests a new target of OTA toxicity. Moreover, the
      identification of the differentially expressed miRNAs provides us a molecular
      insight into the nephrtoxicity of OTA.

PMID- 24885636
TI  - Tumor-associated macrophage-derived IL-6 and IL-8 enhance invasive activity of
      LoVo cells induced by PRL-3 in a KCNN4 channel-dependent manner.
AB  - BACKGROUND: Tumor-associated macrophages (TAMs) are known to promote cancer
      progression and metastasis through the release of a variety of cytokines.
      Phosphatase of regenerating liver (PRL-3) has been considered as a marker of
      colorectal cancer (CRC) liver metastasis. Our previous research suggests that PRL
      3 can enhance the metastasis of CRC through the up-regulation of intermediate
      conductance Ca2+-activated K+ (KCNN4) channel, which is dependent on the
      autocrine secretion of tumor necrosis factor-alpha (TNF-alpha). However, whether
      TAMs participate in the progression and metastasis of CRC induced by PRL-3
      remains unknown. METHODS: We used flow cytometry, coculture, western blotting,
      invasion assays, real-time quantitative PCR, chromatin immunoprecipitation,
      luciferase reporter assays, and immunofluorescence staining to determine the
      effect of TAMs on the ability of PRL-3 to promote invasiveness of CRC cells.
      RESULTS: In this study, we found that TAMs facilitated the metastasis of CRC
      induced by PRL-3. When TAMs were cocultured with CRC cells, the expression of
      KCNN4 was increased in TAMs and the invasion of CRC cells was enhanced.
      Furthermore, cytokines that were secreted by TAMs, such as IL-6 and IL-8, were
      also significantly increased. This response was attenuated by treating TAMs with
      the KCNN4 channel-specific inhibitor, 1-[(2-chlorophenyl) diphenylmethyl]-1H
      pyrazole (TRAM-34), which suggested that KCNN4 channels may be involved in
      inducing the secretion of IL-6 and IL-8 by TAMs and improving CRC cell
      invasiveness. Moreover, the expression of KCNN4 channels in TAMs was regulated
      through the NF-kappaB signal pathway, which is activated by TNF-alpha from CRC
      cells. Immunofluorescence analysis of colorectal specimens indicated that IL-6
      and IL-8 double positive cells in the stroma showed positive staining for the TAM
      marker CD68, suggesting that TAMs produce IL-6 and IL-8. Increased numbers of
      these cells correlated with higher clinical stage. CONCLUSIONS: Our findings
      suggested that TAMs participate in the metastasis of CRC induced by PRL-3 through
      the TNF-alpha mediated secretion of IL-6 and IL-8 in a paracrine manner.

PMID- 24885637
TI  - A randomized controlled trial of nonoperative treatment versus open reduction and
      internal fixation for stable, displaced, partial articular fractures of the
      radial head: the RAMBO trial.
AB  - BACKGROUND: The choice between operative or nonoperative treatment is questioned
      for partial articular fractures of the radial head that have at least 2
      millimeters of articular step-off on at least one radiograph (defined as
      displaced), but less than 2 millimeter of gap between the fragments (defined as
      stable) and that are not associated with an elbow dislocation, interosseous
      ligament injury, or other fractures. These kinds of fractures are often
      classified as Mason type-2 fractures. Retrospective comparative studies suggest
      that operative treatment might be better than nonoperative treatment, but the
      long-term results of nonoperative treatment are very good. Most experts agree
      that problems like reduced range of motion, painful crepitation, nonunion or bony
      ankylosis are infrequent with both nonoperative and operative treatment of an
      isolated displaced partial articular fracture of the radial head, but determining
      which patients will have problems is difficult. A prospective, randomized
      comparison would help minimize bias and determine the balance between operative
      and nonoperative risks and benefits. METHODS/DESIGN: The RAMBO trial (Radial Head
      - Amsterdam - Amphia - Boston - Others) is an international prospective,
      randomized, multicenter trial. The primary objective of this study is to compare
      patient related outcome defined by the 'Disabilities of Arm, Shoulder and Hand
      (DASH) score' twelve months after injury between operative and nonoperative
      treated patients. Adult patients with partial articular fractures of the radial
      head that comprise at least 1/3rd of the articular surface, have >= 2 millimeters
      of articular step-off but less than 2 millimeter of gap between the fragments
      will be enrolled. Secondary outcome measures will be the Mayo Elbow Performance
      Index (MEPI), the Oxford Elbow Score (OES), pain intensity through the 'Numeric
      Rating Scale', range of motion (flexion arc and rotational arc), radiographic
      appearance of the fracture (heterotopic ossification, radiocapitellar and
      ulnohumeral arthrosis, fracture healing, and signs of implant loosening or
      breakage) and adverse events (infection, nerve injury, secondary interventions)
      after one year. DISCUSSION: The successful completion of this trial will provide
      evidence on the best treatment for stable, displaced, partial articular fractures
      of the radial head. TRIAL REGISTRATION: The trial is registered at the Dutch
      Trial Register: NTR3413.

PMID- 24885638
TI  - Defining the full tomato NB-LRR resistance gene repertoire using genomic and cDNA
      RenSeq.
AB  - BACKGROUND: The availability of draft crop plant genomes allows the prediction of
      the full complement of genes that encode NB-LRR resistance gene homologs,
      enabling a more targeted breeding for disease resistance. Recently, we developed
      the RenSeq method to reannotate the full NB-LRR gene complement in potato and to
      identify novel sequences that were not picked up by the automated gene prediction
      software. Here, we established RenSeq on the reference genome of tomato (Solanum
      lycopersicum) Heinz 1706, using 260 previously identified NB-LRR genes in an
      updated Solanaceae RenSeq bait library. RESULT: Using 250-bp MiSeq reads after
      RenSeq on genomic DNA of Heinz 1706, we identified 105 novel NB-LRR sequences.
      Reannotation included the splitting of gene models, combination of partial genes
      to a longer sequence and closing of assembly gaps. Within the draft S.
      pimpinellifolium LA1589 genome, RenSeq enabled the annotation of 355 NB-LRR
      genes. The majority of these are however fragmented, with 5'- and 3'-end located
      on the edges of separate contigs. Phylogenetic analyses show a high conservation
      of all NB-LRR classes between Heinz 1706, LA1589 and the potato clone DM,
      suggesting that all sub-families were already present in the last common
      ancestor. A phylogenetic comparison to the Arabidopsis thaliana NB-LRR complement
      verifies the high conservation of the more ancient CCRPW8-type NB-LRRs. Use of
      RenSeq on cDNA from uninfected and late blight-infected tomato leaves allows the
      avoidance of sequence analysis of non-expressed paralogues. CONCLUSION: RenSeq is
      a promising method to facilitate analysis of plant resistance gene complements.
      The reannotated tomato NB-LRR complements, phylogenetic relationships and
      chromosomal locations provided in this paper will provide breeders and scientists
      with a useful tool to identify novel disease resistance traits. cDNA RenSeq
      enables for the first time next-gen sequencing approaches targeted to this very
      low-expressed gene family without the need for normalization.

PMID- 24885640
TI  - The inverse association between relative abundances of oleic acid and arachidonic
      acid is related to alpha -linolenic acid.
AB  - BACKGROUND: Many health effects of oils rich in oleic acid (OA, 18:1 n9) seem to
      be opposite those of arachidonic acid (AA, 20:4 n6), i.e. concerning
      cardiovascular risk. In recent studies in humans and in the rat we observed that
      percentages of OA and AA were inversely related, raising the question of whether
      the inverse association is a general one, and how it might be explained. In the
      present work we examine whether percentages of OA and AA are inversely associated
      in breast muscle lipids of chickens, and whether alpha-linolenic acid (ALA) may
      be related to the OA/AA ratio. METHODS: The study group consisted of 163
      chickens. Breast muscle was collected, and the concentration of fatty acids in
      muscle lipids was determined using gas chromatography. We studied association
      between fatty acids using bivariate correlations (Pearson) and linear regression.
      Synthesis of OA from stearic acid (Stear) was estimated using the OA/Stear ratio,
      and formation of AA from linoleic acid (LA) was estimated by the AA/LA ratio.
      RESULTS: We found a strong inverse relationship (r = -0.942, p < 0.001; n = 163)
      between % OA and % AA in breast muscle lipids of the chickens. There was an
      inverse association (r = -0.887, p < 0.001) between the OA/Stearic acid ratio,
      estimating Delta9 desaturase, and the AA/LA ratio, estimating
      desaturases/elongase activities. Furthermore, there was a strong negative
      association between % AA and the OA/Stearic acid ratio (r = -0.925, p < 0.001),
      and % OA correlated negatively (r = -0.914, p < 0.001) with the AA/LA ratio. ALA
      was positively associated (r = 0.956, p < 0.001) with the OA/AA ratio, and this
      association prevailed when controlling for the other fatty acids. ALA was
      positively associated (r = 0.857, p < 0.001) with the OA/Stear ratio, but was
      negatively related (r = -0.827, p < 0.001) to the AA/LA ratio. CONCLUSIONS: The
      relative abundances of OA and AA that are inversely related in muscle lipids of
      chickens may be explained by a feedback regulation between the synthesis of OA
      and AA, and related to ALA, which seems to stimulate formation of OA, and inhibit
      synthesis of AA, but further studies are required to clarify whether this
      hypothesis is valid.

PMID- 24885639
TI  - Construction of a SNP-based genetic linkage map in cultivated peanut based on
      large scale marker development using next-generation double-digest restriction
      site-associated DNA sequencing (ddRADseq).
AB  - BACKGROUND: Cultivated peanut, or groundnut (Arachis hypogaea L.), is an
      important oilseed crop with an allotetraploid genome (AABB, 2n=4x=40). In recent
      years, many efforts have been made to construct linkage maps in cultivated
      peanut, but almost all of these maps were constructed using low-throughput
      molecular markers, and most show a low density, directly influencing the value of
      their applications. With advances in next-generation sequencing (NGS) technology,
      the construction of high-density genetic maps has become more achievable in a
      cost-effective and rapid manner. The objective of this study was to establish a
      high-density single nucleotide polymorphism (SNP)-based genetic map for
      cultivated peanut by analyzing next-generation double-digest restriction-site
      associated DNA sequencing (ddRADseq) reads. RESULTS: We constructed reduced
      representation libraries (RRLs) for two A. hypogaea lines and 166 of their
      recombinant inbred line (RIL) progenies using the ddRADseq technique.
      Approximately 175 gigabases of data containing 952,679,665 paired-end reads were
      obtained following Solexa sequencing. Mining this dataset, 53,257 SNPs were
      detected between the parents, of which 14,663 SNPs were also detected in the
      population, and 1,765 of the obtained polymorphic markers met the requirements
      for use in the construction of a genetic map. Among 50 randomly selected in
      silico SNPs, 47 were able to be successfully validated. One linkage map was
      constructed, which was comprised of 1,685 marker loci, including 1,621 SNPs and
      64 simple sequence repeat (SSR) markers. The map displayed a distribution of the
      markers into 20 linkage groups (LGs A01-A10 and B01-B10), spanning a distance of
      1,446.7 cM. The alignment of the LGs from this map was shown in comparison with a
      previously integrated consensus map from peanut. CONCLUSIONS: This study showed
      that the ddRAD library combined with NGS allowed the rapid discovery of a large
      number of SNPs in the cultivated peanut. The first high density SNP-based linkage
      map for A. hypogaea was generated that can serve as a reference map for
      cultivated Arachis species and will be useful in genetic mapping. Our results
      contribute to the available molecular marker resources and to the assembly of a
      reference genome sequence for the peanut.

PMID- 24885641
TI  - Improving the sensitivity of sample clustering by leveraging gene co-expression
      networks in variable selection.
AB  - BACKGROUND: Many variable selection techniques have been proposed for the
      clustering of gene expression data. While these methods tend to filter out
      irrelevant genes and identify informative genes that contribute to a clustering
      solution, they are based on criteria that do not consider the potential
      interactive influence among individual genes. Motivated by ensemble clustering,
      there is a strong interest in leveraging the structure of gene networks for gene
      selection, so that the relationship information between genes can be effectively
      utilized, while the selected genes are expected to preserve all the possible
      clustering structures in the data. RESULTS: We present a new filter method that
      uses the gene connectivity in the gene co-expression network as the evaluation
      criteria for variable selection. The gene connectivity measures the importance of
      the genes in term of their expression similarity with others in the co-expression
      network. The hard threshold and soft threshold transformations are employed to
      construct the gene co-expression networks. Both simulation studies and real data
      analysis have shown that the network based on soft thresholding is more effective
      in selecting relevant variables and provides better clustering results compared
      to the hard thresholding transformation and two other canonical filter methods
      for variable selection. Furthermore, a new module analysis approach is proposed
      to reveal the higher order organization of the gene space, where the genes of a
      module share significant topological similarity and are associated with a
      consensus partition of the sample space. We demonstrate that the identified
      modules can lead to biologically meaningful sample partitions that might be
      missed by other methods. CONCLUSIONS: By leveraging the structure of gene co
      expression network, first we propose a variable selection method that selects
      individual genes with top connectivity. Both simulation studies and real data
      application have demonstrated that our method has better performance in terms of
      the reliability of the selected genes and sample clustering results. In addition,
      we propose a module recovery method that can help discover novel sample
      partitions that might be hidden when performing clustering analyses using all
      available genes. The source code of our program is available at
      http://nba.uth.tmc.edu/homepage/liu/netVar/.

PMID- 24885642
TI  - Factors influencing the work passion of Chinese community health service workers:
      an investigation in five provinces.
AB  - BACKGROUND: After the implementation of new healthcare reform, Chinese government
      paid increasing attention to developing community health service (CHS). The
      current focus is mainly on cultivating community general practitioners but paying
      less attention to the working status and occupational demands of in-service CHS
      workers. Work passion is playing an important role for medical workers. With work
      passion, CHS workers' team will become more stable and more effective, ensuring
      the sustainable development of CHS system. At present, the work passion of CHS
      workers is relatively low. Studying on influencing factors of work passion of CHS
      workers, promoting their work passion, and making them keep enthusiasm for work
      are significant. METHODS: A total of 100 CHS organizations were sampled randomly
      in 10 cities from 5 Chinese provinces for this study. A total of 3450 CHS workers
      from these CHS institutions took part in the surveys. Questionnaires were used to
      collect data, including socio-demographic information, work passion and opinion
      on influencing causes, and work-related satisfaction. Pearson chi-square
      statistical method was used to identify the factors related to CHS workers' work
      passion. Binary logistic regression was performed to determine the significant
      factors that influence CHS workers' work passion. RESULTS: A total of 38.77% of
      those who accomplished the questionnaire expressed that they didn't have passion
      for current work. The related factors that influence CHS workers' work passion
      are (1) socio-demographic factors such as age, and years of employment, and (2)
      other work-related factors such as learning and training opportunities,
      compensation packages, work stress, and personal development opportunities. CHS
      workers were most dissatisfied with the balance between remuneration and
      workload, job promotion opportunities. CONCLUSIONS: Based on the results, the
      government should concern for CHS workers' working status and work-related
      demands, pay more attention and meet their demands for reasonable compensation
      packages and self-development, balance the income and workload, provide more
      learning and training opportunities and personal development opportunities for
      CHS workers, in order to promote CHS workers' work satisfaction, improve their
      work passion and enthusiasm.

PMID- 24885643
TI  - Are gait variability and stability measures influenced by directional changes?
AB  - BACKGROUND: Many gait variability and stability measures have been proposed in
      the literature, with the aim to quantify gait impairment, degree of neuro-motor
      control and balance disorders in healthy and pathological subjects. These
      measures are often obtained from lower trunk acceleration data, typically
      acquired during rectilinear gait, but relevant experimental protocols and data
      processing techniques lack in standardization. Since directional changes
      represent an essential aspect of gait, the assessment of their influence on such
      measures is essential for standardization. In addition, their investigation is
      needed to evaluate the applicability of these measures in laboratory trials and
      in daily life activity analysis. A further methodological aspect to be
      standardized concerns the assessment of the sampling frequency, which could
      affect stability measures. The aim of the present study was hence to assess if
      gait variability and stability measures are affected by directional changes, and
      to evaluate the influence of sampling frequency of trunk acceleration data on the
      results. METHODS: Fifty-one healthy young adults performed a 6-minute walk test
      along a 30 m straight pathway, turning by 180 deg at each end of the pathway.
      Nine variability and stability measures (Standard deviation, Coefficient of
      variation, Poincare plots, maximum Floquet multipliers, short-term Lyapunov
      exponents, Recurrence quantification analysis, Multiscale entropy, Harmonic ratio
      and Index of harmonicity) were calculated on stride duration and trunk
      acceleration data (acquired at 100 Hz and 200 Hz) coming from straight walking
      windows and from windows including both straight walking and the directional
      change. RESULTS: Harmonic ratio was the only measure that resulted to be affected
      by directional changes and sampling frequency, decreasing with the presence of a
      directional change task. HR was affected in the AP and V directions for the 200
      Hz, but only in AP direction for the 100 Hz group. CONCLUSION: Multiscale
      entropy, short term Lyapunov exponents and Recurrence quantification analysis
      were generally not affected by directional changes nor by sampling frequency, and
      could contribute to the definition of a fall risk index in free-walking
      conditions.

PMID- 24885644
TI  - Changed processing of visual sexual stimuli under GnRH-therapy--a single case
      study in pedophilia using eye tracking and fMRI.
AB  - BACKGROUND: Antiandrogen therapy (ADT) has been used for 30 years to treat
      pedophilic patients. The aim of the treatment is a reduction in sexual drive and,
      in consequence, a reduced risk of recidivism. Yet the therapeutic success of
      antiandrogens is uncertain especially regarding recidivism. Meta-analyses and
      reviews report only moderate and often mutually inconsistent effects. CASE
      PRESENTATION: Based on the case of a 47 year old exclusively pedophilic forensic
      inpatient, we examined the effectiveness of a new eye tracking method and a new
      functional magnetic resonance imaging (fMRI)-design in regard to the evaluation
      of ADT in pedophiles. We analyzed the potential of these methods in exploring the
      impact of ADT on automatic and controlled attentional processes in pedophiles.
      Eye tracking and fMRI measures were conducted before the initial ADT as well as
      four months after the onset of ADT. The patient simultaneously viewed an image of
      a child and an image of an adult while eye movements were measured. During the
      fMRI-measure the same stimuli were presented subliminally. Eye movements
      demonstrated that controlled attentional processes change under ADT, whereas
      automatic processes remained mostly unchanged. We assume that these results
      reflect either the increased ability of the patient to control his eye movements
      while viewing prepubertal stimuli or his better ability to manipulate his answer
      in a socially desirable manner. Unchanged automatic attentional processes could
      reflect the stable pedophilic preference of the patient. Using fMRI, the
      subliminal presentation of sexually relevant stimuli led to changed activation
      patterns under the influence of ADT in occipital and parietal brain regions, the
      hippocampus, and also in the orbitofrontal cortex. We suggest that even at an
      unconscious level ADT can lead to changed processing of sexually relevant
      stimuli, reflecting changes of cognitive and perceptive automatic processes.
      CONCLUSION: We are convinced that our experimental designs using eye tracking and
      fMRI could prospectively add additional and valuable information in the
      evaluation of ADT in paraphilic patients and sex offenders. But with respect to
      the limited significance of this single case study, these first results are
      preliminary and further studies have to be conducted with healthy subjects and
      patients.

PMID- 24885645
TI  - Rehabilitation of the hemiparetic gait by nociceptive withdrawal reflex-based
      functional electrical therapy: a randomized, single-blinded study.
AB  - BACKGROUND: Gait deficits are very common after stroke and improved therapeutic
      interventions are needed. The objective of this study was therefore to
      investigate the therapeutic use of the nociceptive withdrawal reflex to support
      gait training in the subacute post-stroke phase. METHODS: Individuals were
      randomly allocated to a treatment group that received physiotherapy-based gait
      training supported by withdrawal reflex stimulation and a control group that
      received physiotherapy-based gait training alone. Electrical stimuli delivered to
      the arch of the foot elicited the withdrawal reflex at heel-off with the purpose
      of facilitating the initiation and execution of the swing phase. Gait was
      assessed before and immediately after finishing treatment, and one month and six
      months after finishing treatment. Assessments included the Functional Ambulation
      Category (FAC) test, the preferred and maximum gait velocities, the duration of
      the stance phase in the hemiparetic side, the duration of the gait cycle, and the
      stance time symmetry ratio. RESULTS: The treatment group showed an improved post
      treatment preferred walking velocity (p < 0.001) and fast walking velocity (p <
      0.001) compared to the control group. Furthermore, subjects in the treatment
      group with severe walking impairment at inclusion time showed the best
      improvement as assessed by a longer duration of the stance phase in the
      hemiparetic side (p < 0.002) and a shorter duration of the gait cycle (p <
      0.002). The stance time symmetry ratio was significantly better for the treatment
      than the control group after finishing training (p < 0.02). No differences
      between groups were detected with the FAC test after finishing training (p =
      0.09). CONCLUSION: Withdrawal reflex-based functional electrical therapy was
      useful in the rehabilitation of the hemiparetic gait of severely impaired
      patients.

PMID- 24885646
TI  - Expedient synthesis of alpha-(2-azaheteroaryl) acetates via the addition of silyl
      ketene acetals to azine-N-oxides.
AB  - A new and expedient synthesis of alpha-(2-azaheteroaryl) acetates is presented.
      The reaction proceeds rapidly under mild conditions via the addition of silyl
      ketene acetals to azine-N-oxides in the presence of the phosphonium salt PyBroP.
      This procedure affords diverse alpha-(2-azaheteroaryl) acetates which are highly
      desirable components/building blocks in molecules of pharmaceutical interest but
      are traditionally challenging to synthesize via contemporary methods. The
      reaction optimization and mechanism as well as a novel electronically enhanced
      PyBroP derivative are described. 

PMID- 24885647
TI  - Infected or not: are PCR-positive oropharyngeal swabs indicative of low
      pathogenic influenza A virus infection in the respiratory tract of Mallard Anas
      platyrhynchos?
AB  - Detection of influenza virus in oropharyngeal swabs collected during wild bird
      surveillance is assumed to represent respiratory infection, although intestine is
      the main site of infection. We tested this assumption by histological examination
      of the respiratory tract of wild Mallards with virus-positive oropharyngeal
      swabs. Thirty-two of 125 Mallards tested had viral-RNA positive oropharyngeal
      swabs. The respiratory tracts of four Mallards with the most virus were examined
      in detail by immunohistochemistry. None had detectable virus antigen in the
      respiratory tract, suggesting it was not infected. An alternative explanation is
      that the oropharynx was contaminated with virus through feeding in surface water
      or through preening.

PMID- 24885648
TI  - Acute gastroesophageal intussusception in a juvenile Australian Shepherd dog:
      endoscopic treatment and long-term follow-up.
AB  - BACKGROUND: Canine gastroesophageal intussusception (GEI) is a rare and
      potentially fatal disease usually affecting puppies or young dogs < 3 months of
      age and of medium to large breeds. Surgical intervention has been advocated as
      the therapy of choice by most authors. Endoscopic treatment may offer an
      advantageous or alternative method of treatment. CASE PRESENTATION: GEI was
      diagnosed in a nine-week-old Australian Shepherd dog with an acute onset of
      vomiting and regurgitation and compatible radiographic findings on thoracic
      radiography. Treatment consisted of endoscopic gastric repositioning and
      placement of a percutaneous endoscopic gastrostomy (PEG) tube to prevent repeated
      dislocation of the stomach, and to allow for nutritional supplementation During a
      follow-up period of eight months, thoracic radiographs were obtained showing
      persistent esophageal dilatation in the absence of compatible clinical signs.
      CONCLUSION: Endoscopic intervention is an effective, alternative in selected
      canine GEI- cases, allowing for rapid, minimally invasive confirmation of
      diagnosis and therapy. After initial treatment, radiographic long-term follow-up
      seems prudent even in asymptomatic patients.

PMID- 24885651
TI  - Medical hypnotherapy for pain management.
AB  - Questions from patients about pain conditions and analgesic pharmacotherapy and
      responses from authors are presented to help educate patients and make them more
      effective self-advocates. Hypnotherapy, its uses and process, and certification
      and training of hypnotherapy professionals are addressed.

PMID- 24885650
TI  - "If you can't treat HPV, why test for it?" Women's attitudes to the changing face
      of cervical cancer prevention: a focus group study.
AB  - BACKGROUND: The relationship between infection with high-risk strains of human
      papillomavirus (HPV) and cervical cancer is transforming prevention through HPV
      vaccination and HPV oncogenic testing. In Ireland, a national cervical cancer
      screening programme and HPV vaccination were recently launched; HPV testing is
      currently being integrated into the screening programme. Women's views on the
      transformation of cervical cancer prevention have been relatively little
      investigated. METHODS: Using qualitative focus groups, we determined women's
      knowledge, attitudes towards, and acceptability of cervical cancer screening, HPV
      oncogenic testing and vaccination of HPV. Fifty nine women, recruited through
      primary care in Ireland, participated in ten focus groups. A dynamic topic guide
      was developed from literature reviewed. Women were provided with standardised
      information about HPV infection, HPV testing. Discussion transcripts were
      analysed thematically. RESULTS: The primary themes that emerged regarding HPV
      infection were: knowledge, emotional response and societal influences; especially
      those of healthcare practitioners. Knowledge, logistics, and psychological impact
      were the primary themes relating to HPV testing. Women's attitudes towards HPV
      testing changed during discussion as issues were explored, thus demonstrating the
      complexity of this issue; lack of existing treatment for HPV infection influenced
      women's attitudes, attachment to existing cervical cancer screening also was a
      significant factor. CONCLUSIONS: Women currently have a strong attachment to
      cytology and any changes towards HPV primary testing will need to be managed
      carefully. To ensure that future cervical cancer prevention strategies will be
      acceptable to women, sufficient thought will have to be given to information
      provision and education. We identified the importance to women of healthcare
      practitioners' opinions regarding HPV. Appropriate and timely information on HPV
      will be crucial in order to minimise possible psychological effects women may
      have.

PMID- 24885649
TI  - The second generation of HIV-1 vertically exposed infants: a case series from the
      Italian Register for paediatric HIV infection.
AB  - BACKGROUND: In the Highly Active Antiretroviral Therapy (HAART) era, the
      prognosis of children perinatally infected with HIV-1 has significantly improved,
      so the number of perinatally-infected females entering child-bearing age and
      experiencing motherhood is increasing. METHODS: A description of the medical
      history and pregnancy outcomes of women with perinatal acquired HIV-1 infection
      enrolled in the Italian Register for HIV infection in Children. RESULTS: Twenty
      three women had 29 pregnancies. They had started an antiretroviral therapy at a
      median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a
      median of 4 therapeutic regimens (IQR 2-6). Twenty women (87%) had taken
      zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21
      pregnancies a protease inhibitor-based regimen was used. At delivery, the median
      of CD4+ T lymphocytes was 450/MUL (IQR 275-522), and no viral load was detectable
      in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered
      through caesarean section (median gestational age: 38 weeks, IQR 36-38, median
      birth weight: 2550 grams, IQR 2270 - 3000). Intravenous AZT was administered
      during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR
      31 - 42), with no adverse events reported. No child acquired HIV-1 infection.
      CONCLUSIONS: Despite a long history of maternal infection, multiple
      antiretroviral regimens and, perhaps, the development of drug-resistant viruses,
      the risk of mother-to-child transmission does not seem to have increased among
      the second-generation of HIV-1 exposed infants.

PMID- 24885652
TI  - Comparison of two preclinical myocardial infarct models: coronary coil deployment
      versus surgical ligation.
AB  - BACKGROUND: Despite recent advances, myocardial infarction (MI) remains the
      leading cause of death worldwide. Pre-clinical animal models that closely mimic
      human MI are pivotal for a quick translation of research and swine have
      similarities in anatomy and physiology. Here, we compared coronary surgical
      ligation versus coil embolization MI models in swine. METHODS: Fifteen animals
      were randomly distributed to undergo surgical ligation (n=7) or coil embolization
      (n=8). We evaluated infarct size, scar fibrosis, inflammation, myocardial
      vascularization, and cardiac function by magnetic resonance imaging (MRI).
      RESULTS: Thirty-five days after MI, there were no differences between the models
      in infarct size (P=0.53), left ventricular (LV) ejection fraction (P=0.19), LV
      end systolic volume (P=0.22), LV end diastolic volume (P=0.84), and cardiac
      output (P=0.89). Histologically, cardiac scars did not differ and the collagen
      content, collagen type I (I), collagen type III (III), and the I/III ratio were
      similar in both groups. Inflammation was assessed using specific anti-CD3 and
      anti-CD25 antibodies. There was similar activation of inflammation throughout the
      heart after coil embolization (P=0.78); while, there were more activated
      lymphocytes in the infarcted myocardium in the surgical occlusion model (P=0.02).
      Less myocardial vascularization in the infarction areas compared with the border
      and remote zones only in coil embolization animals was observed (P=0.004 and
      P=0.014, respectively). CONCLUSIONS: Our results support that surgical occlusion
      and coil embolization MI models generate similar infarct size, cardiac function
      impairment, and myocardial fibrosis; although, inflammation and myocardial
      vascularization levels were closer to those found in humans when coil
      embolization was performed.

PMID- 24885653
TI  - Decision-making on intra-household allocation of bed nets in Uganda: do
      households prioritize the most vulnerable members?
AB  - BACKGROUND: Access to insecticide-treated bed nets has increased substantially in
      recent years, but ownership and use remain well below 100% in many malaria
      endemic areas. Understanding decision-making around net allocation in households
      with too few nets is essential to ensuring protection of the most vulnerable.
      This study explores household net allocation preferences and practices across
      four districts in Uganda. METHODS: Data collection consisted of eight focus group
      discussions, twelve in-depth interviews, and a structured questionnaire to
      inventory 107 sleeping spaces in 28 households. RESULTS: In focus group
      discussions and in-depth interviews, participants almost unanimously stated that
      pregnant women, infants, and young children should be prioritized when allocating
      nets. However, sleeping space surveys reveal that heads of household sometimes
      receive priority over children less than five years of age when households have
      too few nets to cover all members. CONCLUSIONS: When asked directly, most net
      owners highlight the importance of allocating nets to the most biologically
      vulnerable household members. This is consistent with malaria behaviour change
      and health education messages. In actual allocation, however, factors other than
      biological vulnerability may influence who does and does not receive a net.

PMID- 24885655
TI  - Patient guardians as an instrument for person centered care.
AB  - Person-centered care involves keeping the person at the center of the care
      planning and decision-making process. While the theory behind person-centered
      care is commonly shared, its application in healthcare settings is more
      challenging. In a number of African countries, a lesson emerges involving the
      application of person-centered care through the use of patient guardians. Patient
      guardians, often family or close friends, act as an extension of the patient's
      hospital care team. Medical teams engage with these self-designated individuals
      who invest their time and efforts in the care of the patient. More importantly,
      the guardian continues this role and relationship when the patient is released
      from the hospital to return home. Healthcare workers view patient guardians as a
      valuable resource. In a structured manner, guardians become stewards of
      information regarding topics such as hand hygiene and infection control. The
      knowledge gained can help the recovering patient upon discharge and potentially
      spread the information to others in the community. Further study of this model
      may show clear applicability to help improve health literacy in underserved
      settings in both low-income and high-income countries. 

PMID- 24885654
TI  - Total thyroidectomy without prophylactic central neck dissection in clinically
      node-negative papillary thyroid cancer: is it an adequate treatment?
AB  - BACKGROUND: Cervical lymph node metastases in papillary thyroid cancer are
      common. Although central neck dissection is indicated in clinically nodal
      positive disease, it remains controversial in patients with no clinical evidence
      of nodal metastasis. The aim of this retrospective study was to determine the
      outcomes of clinically lymph node-negative patients with papillary thyroid cancer
      who underwent total thyroidectomy without a central neck dissection, in order to
      determine the rates of recurrence and reoperation in these patients compared with
      a group of patients submitted to total thyroidectomy with central neck
      dissection. METHODS: Two-hundred and eighty-five patients undergoing total
      thyroidectomy with preoperative diagnosis of papillary thyroid cancer, in the
      absence of suspicious nodes, were divided in two groups: those who underwent a
      thyroidectomy only (group A; n=220) and those who also received a central neck
      dissection (group B; n=65). RESULTS: Six cases (2.1%) of nodal recurrence were
      observed: 4 in group A and 2 in group B. Tumor histology was associated with risk
      of recurrence: Hurthle cell-variant and tall cell-variant carcinomas were
      associated with a high risk of recurrence. Multifocality and extrathyroidal
      invasion also presented a higher risk, while smaller tumors were at lower risk.
      CONCLUSIONS: The role of prophylactic central lymph node dissection in the
      management of papillary thyroid cancer remains controversial. Total thyroidectomy
      appears to be an adequate treatment for clinically node-negative papillary
      thyroid cancer. Prophylactic central neck dissection could be considered for the
      more appropriate selection of patients for radioiodine treatment and should be
      reserved for high-risk patients only. No clinical or pathological factors are
      able to predict with any certainty the presence of nodal metastasis. In our
      experience, tumor size, some histological types, multifocality, and locoregional
      infiltration are related to an increased risk of recurrence. The potential use of
      molecular markers will hopefully offer a further strategy to stratify the risk of
      recurrence in patients with papillary thyroid cancer and allow a more tailored
      approach to offer prophylactic central neck dissection to patients with the
      greatest benefit. Multi-institutional larger studies with longer follow-up
      periods are necessary to draw definitive conclusions.

PMID- 24885656
TI  - A model reduction method for biochemical reaction networks.
AB  - BACKGROUND: In this paper we propose a model reduction method for biochemical
      reaction networks governed by a variety of reversible and irreversible enzyme
      kinetic rate laws, including reversible Michaelis-Menten and Hill kinetics. The
      method proceeds by a stepwise reduction in the number of complexes, defined as
      the left and right-hand sides of the reactions in the network. It is based on the
      Kron reduction of the weighted Laplacian matrix, which describes the graph
      structure of the complexes and reactions in the network. It does not rely on
      prior knowledge of the dynamic behaviour of the network and hence can be
      automated, as we demonstrate. The reduced network has fewer complexes, reactions,
      variables and parameters as compared to the original network, and yet the
      behaviour of a preselected set of significant metabolites in the reduced network
      resembles that of the original network. Moreover the reduced network largely
      retains the structure and kinetics of the original model. RESULTS: We apply our
      method to a yeast glycolysis model and a rat liver fatty acid beta-oxidation
      model. When the number of state variables in the yeast model is reduced from 12
      to 7, the difference between metabolite concentrations in the reduced and the
      full model, averaged over time and species, is only 8%. Likewise, when the number
      of state variables in the rat-liver beta-oxidation model is reduced from 42 to
      29, the difference between the reduced model and the full model is 7.5%.
      CONCLUSIONS: The method has improved our understanding of the dynamics of the two
      networks. We found that, contrary to the general disposition, the first few
      metabolites which were deleted from the network during our stepwise reduction
      approach, are not those with the shortest convergence times. It shows that our
      reduction approach performs differently from other approaches that are based on
      time-scale separation. The method can be used to facilitate fitting of the
      parameters or to embed a detailed model of interest in a more coarse-grained yet
      realistic environment.

PMID- 24885657
TI  - A study protocol: using demand-side financing to meet the birth spacing needs of
      the underserved in Punjab Province in Pakistan.
AB  - BACKGROUND: High fertility rates, unwanted pregnancies, low modern contraceptive
      prevalence and a huge unmet need for contraception adversely affect women's
      health in Pakistan and this problem is compounded by limited access to reliable
      information and quality services regarding birth spacing especially in rural and
      underserved areas. This paper presents a study protocol that describes an
      evaluation of a demand-side financing (DSF) voucher approach which aims to
      increase the uptake of modern contraception among women of the lowest two wealth
      quintiles in Punjab Province, Pakistan. METHODS/DESIGN: This study will use quasi
      experimental design with control arm and be implemented in: six government
      clinics from the Population Welfare Department; 24 social franchise facilities
      branded as 'Suraj' (Sun), led by Marie Stopes Society (a local non-governmental
      organization); and 12 private sector clinics in Chakwal, Mianwali and Bhakkar
      districts. The study respondents will be interviewed at baseline and endline
      subject to voluntary acceptance and medical eligibility. In addition, health
      service data will record each client visit during the study period. DISCUSSION:
      The study will examine the impact of vouchers in terms of increasing the uptake
      of modern contraception by engaging private and public sector service providers
      (mid-level and medical doctors). If found effective, this approach can be a
      viable solution to satisfying the current demand and meeting the unmet need for
      contraception, particularly among the poorest socio-economic group.

PMID- 24885659
TI  - A cognitive perspective on health systems integration: results of a Canadian
      Delphi study.
AB  - BACKGROUND: Ongoing challenges to healthcare integration point toward the need to
      move beyond structural and process issues. While we know what needs to be done to
      achieve integrated care, there is little that informs us as to how. We need to
      understand how diverse organizations and professionals develop shared knowledge
      and beliefs - that is, we need to generate knowledge about normative integration.
      We present a cognitive perspective on integration, based on shared mental model
      theory, that may enhance our understanding and ability to measure and influence
      normative integration. The aim of this paper is to validate and improve the
      Mental Models of Integrated Care (MMIC) Framework, which outlines important
      knowledge and beliefs whose convergence or divergence across stakeholder groups
      may influence inter-professional and inter-organizational relations. METHODS: We
      used a two-stage web-based modified Delphi process to test the MMIC Framework
      against expert opinion using a random sample of participants from Canada's
      National Symposium on Integrated Care. Respondents were asked to rate the
      framework's clarity, comprehensiveness, usefulness, and importance using seven
      point ordinal scales. Spaces for open comments were provided. Descriptive
      statistics were used to describe the structured responses, while open comments
      were coded and categorized using thematic analysis. The Kruskall-Wallis test was
      used to examine cross-group agreement by level of integration experience, current
      workplace, and current role. RESULTS: In the first round, 90 individuals
      responded (52% response rate), representing a wide range of professional roles
      and organization types from across the continuum of care. In the second round, 68
      individuals responded (75.6% response rate). The quantitative and qualitative
      feedback from experts was used to revise the framework. The re-named "Integration
      Mindsets Framework" consists of a Strategy Mental Model and a Relationships
      Mental Model, comprising a total of nineteen content areas. CONCLUSIONS: The
      Integration Mindsets Framework draws the attention of researchers and
      practitioners to how various stakeholders think about and conceptualize
      integration. A cognitive approach to understanding and measuring normative
      integration complements dominant cultural approaches and allows for more fine
      grained analyses. The framework can be used by managers and leaders to facilitate
      the interpretation, planning, implementation, management and evaluation of
      integration initiatives.

PMID- 24885658
TI  - Gene expression profiling of 49 human tumor xenografts from in vitro culture
      through multiple in vivo passages--strategies for data mining in support of
      therapeutic studies.
AB  - BACKGROUND: Development of cancer therapeutics partially depends upon selection
      of appropriate animal models. Therefore, improvements to model selection are
      beneficial. RESULTS: Forty-nine human tumor xenografts at in vivo passages 1, 4
      and 10 were subjected to cDNA microarray analysis yielding a dataset of 823
      Affymetrix HG-U133 Plus 2.0 arrays. To illustrate mining strategies supporting
      therapeutic studies, transcript expression was determined: 1) relative to other
      models, 2) with successive in vivo passage, and 3) during the in vitro to in vivo
      transition. Ranking models according to relative transcript expression in vivo
      has the potential to improve initial model selection. For example, combining p53
      tumor expression data with mutational status could guide selection of tumors for
      therapeutic studies of agents where p53 status purportedly affects efficacy
      (e.g., MK-1775). The utility of monitoring changes in gene expression with
      extended in vivo tumor passages was illustrated by focused studies of drug
      resistance mediators and receptor tyrosine kinases. Noteworthy observations
      included a significant decline in HCT-15 colon xenograft ABCB1 transporter
      expression and increased expression of the kinase KIT in A549 with serial
      passage. These trends predict sensitivity to agents such as paclitaxel (ABCB1
      substrate) and imatinib (c-KIT inhibitor) would be altered with extended passage.
      Given that gene expression results indicated some models undergo profound changes
      with in vivo passage, a general metric of stability was generated so models could
      be ranked accordingly. Lastly, changes occurring during transition from in vitro
      to in vivo growth may have important consequences for therapeutic studies since
      targets identified in vitro could be over- or under-represented when tumor cells
      adapt to in vivo growth. A comprehensive list of mouse transcripts capable of
      cross-hybridizing with human probe sets on the HG-U133 Plus 2.0 array was
      generated. Removal of the murine artifacts followed by pairwise analysis of in
      vitro cells with respective passage 1 xenografts and GO analysis illustrates the
      complex interplay that each model has with the host microenvironment.
      CONCLUSIONS: This study provides strategies to aid selection of xenograft models
      for therapeutic studies. These data highlight the dynamic nature of xenograft
      models and emphasize the importance of maintaining passage consistency throughout
      experiments.

PMID- 24885660
TI  - Sensitivity of fever for diagnosis of clinical malaria in a Kenyan area of
      unstable, low malaria transmission.
AB  - BACKGROUND: Malaria in highland areas of Kenya affects children and adults. Local
      clinicians include symptoms other than fever when screening for malaria because
      they believe that fever alone does not capture all cases of malaria. METHODS:
      Individuals who presented to dispensaries in a highland Kenya site of low,
      unstable malaria transmission from 2007-2011 with 1 or more of 11 symptoms were
      tested by microscopy for malaria. Clinical malaria was defined as asexual
      Plasmodium falciparum infection on peripheral blood smear in an individual with
      any screening symptom. Asymptomatic P. falciparum infection was assessed in a
      cohort at ten time points to determine the extent to which symptomatic episodes
      with parasitaemia might be attributable to baseline (asymptomatic) parasitaemia
      in the community. RESULTS: 3,420 individuals were screened for malaria, 634 < 5
      years of age and 2,786 >= 5 years of age. For the diagnosis of clinical malaria,
      the symptom of fever had a sensitivity and specificity of 88.9% and15.4% in
      children <5 years, and 55.8% and 54.4% in children >=5 years, respectively.
      Adding the symptom of headache increased sensitivity to 94. 4% in children <5
      years and 96.8% in individuals >=5 years, but decreased specificity to 9.9% and
      11.6%, respectively, and increased the number of individuals who would be tested
      by 6% and 92%, respectively. No combination of symptoms improved upon the
      presence fever or headache for detection of clinical malaria. In the cohort of
      asymptomatic individuals, P. falciparum parasitaemia was infrequent (0.1%).
      CONCLUSION: In areas of low, unstable malaria transmission, fever is a sensitive
      indicator of clinical malaria in children <5 years, but not in older children and
      adults. Adding headache to fever as screening symptom increases sensitivity of
      detection in individuals >=5 years old at the cost of decreased specificity.
      Screening for symptoms in addition to fever may be required to accurately capture
      all cases of clinical malaria in individuals >=5 years old in areas of low
      malaria transmission.

PMID- 24885661
TI  - Mapping QTL conferring resistance in maize to gray leaf spot disease caused by
      Cercospora zeina.
AB  - BACKGROUND: Gray leaf spot (GLS) is a globally important foliar disease of maize.
      Cercospora zeina, one of the two fungal species that cause the disease, is
      prevalent in southern Africa, China, Brazil and the eastern corn belt of the USA.
      Identification of QTL for GLS resistance in subtropical germplasm is important to
      support breeding programmes in developing countries where C. zeina limits
      production of this staple food crop. RESULTS: A maize RIL population (F7:S6) from
      a cross between CML444 and SC Malawi was field-tested under GLS disease pressure
      at five field sites over three seasons in KwaZulu-Natal, South Africa. Thirty QTL
      identified from eleven field trials (environments) were consolidated to seven QTL
      for GLS resistance based on their expression in at least two environments and
      location in the same core maize bins. Four GLS resistance alleles were derived
      from the more resistant parent CML444 (bin 1.10, 4.08, 9.04/9.05, 10.06/10.07),
      whereas the remainder were from SC Malawi (bin 6.06/6.07, 7.02/7.03, 9.06). QTLs
      in bin 4.08 and bin 6.06/6.07 were also detected as joint QTLs, each explained
      more than 11% of the phenotypic variation, and were identified in four and seven
      environments, respectively. Common markers were used to allocate GLS QTL from
      eleven previous studies to bins on the IBM2005 map, and GLS QTL "hotspots" were
      noted. Bin 4.08 and 7.02/7.03 GLS QTL from this study overlapped with hotspots,
      whereas the bin 6.06/6.07 and bin 9.06 QTLs appeared to be unique. QTL for
      flowering time (bin 1.07, 4.09) in this population did not correspond to QTL for
      GLS resistance. CONCLUSIONS: QTL mapping of a RIL population from the subtropical
      maize parents CML444 and SC Malawi identified seven QTL for resistance to gray
      leaf spot disease caused by C. zeina. These QTL together with QTL from eleven
      studies were allocated to bins on the IBM2005 map to provide a basis for
      comparison. Hotspots of GLS QTL were identified on chromosomes one, two, four,
      five and seven, with QTL in the current study overlapping with two of these. Two
      QTL from this study did not overlap with previously reported QTL.

PMID- 24885662
TI  - Vaccination coverage for seasonal influenza among residents and health care
      workers in Norwegian nursing homes during the 2012/13 season, a cross-sectional
      study.
AB  - BACKGROUND: WHO has set a goal of 75% vaccination coverage (VC) for seasonal
      influenza for residents and also recommends immunization for all healthcare
      workers (HCWs) in nursing homes (NHs). We conducted a cross-sectional study to
      estimate the VC for seasonal influenza vaccination in Norwegian NHs in 2012/2013
      since the VC in NHs and HCWs is unknown. METHODS: We gathered information from
      NHs concerning VC for residents and HCWs, and vaccination costs for HCWs, using a
      web-based questionnaire. We calculated VC among NH residents by dividing the
      number of residents vaccinated by the total number of residents for each NH. VC
      among HCWs was similarly calculated by dividing the number of HCWs vaccinated by
      the total number of HCWs for each NH. The association between VC and possible
      demographic variables were explored. RESULTS: Of 910 NHs, 354 (38.9%) responded.
      Median VC per NH was 71.7% (range 0-100) among residents and 0% (range 0-100)
      among HCWs, with 214 (60%) NHs reporting that none of their HCWs was vaccinated.
      Median VC for HCWs in NHs with an annual vaccination campaign was 0% (range 0
      53), compared to when they did not have an annual vaccination campaign 0% (range
      0-12); the distributions in the two groups differed significantly (Mann-Whitney
      U, P = 0.006 two tailed). CONCLUSION: Median influenza VC in Norwegian NHs was
      marginally lower than recommended among residents and exceptionally low among
      HCWs. The VC in HCWs was significantly higher when NHs had an annual vaccination
      campaign. We recommend that NHs implement measures to increase VC among residents
      and HCWs, including vaccination campaigns and studies to identify potential
      barriers to vaccination.

PMID- 24885663
TI  - "If you do vasectomy and come back here weak, I will divorce you": a qualitative
      study of community perceptions about vasectomy in Southern Ghana.
AB  - BACKGROUND: Male involvement in contraceptive use is increasingly becoming a
      global reproductive health issue. Vasectomy is one of the two male modern
      contraceptive methods espoused by the National Family Planning Policy in Ghana.
      Despite these advocacies, there are reports of low patronage of this method in
      Ghana. This study adhering to RATS guidelines on qualitative research therefore
      explored the social and cultural factors that may be affecting the low vasectomy
      uptake in Southern Ghana. METHODS: The study was conducted in Sefwi Bibiani
      Ahwiaso Bekwai (SBAB) District and Komenda-Edina-Eguafo-Abrem (KEEA) Municipal
      area in the Western and Central regions of Ghana respectively. Twelve Focus Group
      Discussions were held with both male and female community members. In-depth
      interviews were also carried out with Community Health Officers (CHOs), Community
      Health Volunteers (CHVs) and health managers at both the district and regional
      levels. The discussions and interviews were recorded, transcribed verbatim and
      analysed using Nvivo 10. RESULTS: The study revealed that vasectomy was perceived
      as an act against God, which was punishable either by death or answerable on
      judgement day. Vasectomy was also perceived to be a form of castration, which can
      make men weak and incapable, thereby unable to satisfy their wives sexually,
      leading to marital conflicts. Women were more concerned about the negative
      effects of vasectomy on men. Cafalgin and panacin which are locally manufactured
      analgesics were perceived to have contraceptive abilities and therefore used by
      men as an alternative to modern contraceptive methods. CONCLUSIONS: Stigma and
      the misconceptions in the community may be accounting for the low vasectomy
      uptake in Ghana despite several advocacy strategies. Women were highly
      influential in a man's decision on vasectomy. This calls for the need to increase
      health education to demystify the misconceptions about vasectomy. Vasectomy
      related campaign messages should target both men and women.

PMID- 24885665
TI  - 3D-MRCP for evaluation of intra- and extrahepatic bile ducts: comparison of
      different acquisition and reconstruction planes.
AB  - BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is an established
      technique for the evaluation of intra- and extrahepatic bile ducts in patients
      with known or suspected hepatobiliary disease. However, the ideal acquisition and
      reconstruction plane for optimal bile duct evaluation with 3D technique has not
      been evaluated. The purpose of our study was to compare different acquisition and
      reconstruction planes of 3D-MRCP for bile duct assessment. METHODS: 34 patients
      (17f/17 m, mean age 41y) referred for MRCP were included in this prospective IRB
      approved study. Respiratory-triggered 3D-T2w-MRCP sequences were acquired in
      coronal and axial plane. Coronal and axial MIP were reconstructed based on each
      dataset (resulting in two coronal and two axial MIP, respectively). Three readers
      in two sessions independently assessed the MIP, regarding visualization of bile
      ducts and image quality. Results were compared (Wilcoxon test). Intra- and
      interobserver variability were calculated (kappa-statistic). RESULTS: In case of
      coronal data acquisition, visualization of bile duct segments was significantly
      better on coronal reconstructed MIP images as compared to axial reconstructed MIP
      (p < 0.05). Regarding visualization, coronal MIP of the coronal acquisition were
      equal to coronal MIP of the axial acquisition (p > 0.05). Image quality of
      coronal and axial datasets did not differ significantly. Intra- and interobserver
      agreement regarding bile duct visualization were moderate to excellent (kappa
      range 0.55-1.00 and 0.42-0.85, respectively). CONCLUSIONS: The results of our
      study suggest that for visualization and evaluation of intra- and extrahepatic
      bile duct segments reconstructed images in coronal orientation are preferable.
      The orientation of the primary dataset (coronal or axial) is negligible.

PMID- 24885664
TI  - Dynamic mechanisms of neuroligin-dependent presynaptic terminal assembly in
      living cortical neurons.
AB  - BACKGROUND: Synapse formation occurs when synaptogenic signals trigger
      coordinated development of pre and postsynaptic structures. One of the best
      characterized synaptogenic signals is trans-synaptic adhesion. However, it
      remains unclear how synaptic proteins are recruited to sites of adhesion. In
      particular, it is unknown whether synaptogenic signals attract synaptic vesicle
      (SV) and active zone (AZ) proteins to nascent synapses or instead predominantly
      function to create sites that are capable of forming synapses. It is also unclear
      how labile synaptic proteins are at developing synapses after their initial
      recruitment. To address these issues, we used long-term, live confocal imaging of
      presynaptic terminal formation in cultured cortical neurons after contact with
      the synaptogenic postsynaptic adhesion proteins neuroligin-1 or SynCAM-1.
      RESULTS: Surprisingly, we find that trans-synaptic adhesion does not attract SV
      or AZ proteins nor alter their transport. In addition, although neurexin (the
      presynaptic partner of neuroligin) typically accumulates over the entire region
      of contact between axons and neuroligin-1-expressing cells, SV proteins
      selectively assemble at spots of enhanced neurexin clustering. The arrival and
      maintenance of SV proteins at these sites is highly variable over the course of
      minutes to hours, and this variability correlates with neurexin levels at
      individual synapses. CONCLUSIONS: Together, our data support a model of
      synaptogenesis where presynaptic proteins are trapped at specific axonal sites,
      where they are stabilized by trans-synaptic adhesion signaling.

PMID- 24885666
TI  - The adaptation of a CTN-1 rabies virus strain to high-titered growth in chick
      embryo cells for vaccine development.
AB  - BACKGROUND: Rabies virus is the causative agent of rabies, a central nervous
      system disease that is almost invariably fatal. Currently vaccination is the most
      effective strategy for preventing rabies, and vaccines are most commonly produced
      from cultured cells. Although the vaccine strains employed in China include CTN,
      aG, PM and PV, there are no reports of strains that are adapted to primary chick
      embryo cells for use in human rabies prevention in China. RESULTS: Rabies virus
      strain CTN-1 V was adapted to chick embryo cells by serial passage to obtain the
      CTNCEC25 strain. A virus growth curve demonstrated that the CTNCEC25 strain
      achieved high titers in chick embryo cells and was nonpathogenic to adult mice by
      intracerebral inoculation. A comparison of the structural protein genes of the
      CTNCEC25 strain and the CTN-1 V strain identified eight amino acid changes in the
      mature M, G and L proteins. The immunogenicity of the CTNCEC25 strain increased
      with the adaptation process in chick embryo cells and conferred high protective
      efficacy. The inactivated vaccine induced high antibody responses and provided
      full protection from an intramuscular challenge in adult mice. CONCLUSIONS: This
      is the first description of a CTNCEC25 strain that was highly adapted to chick
      embryo cells, and both its in vitro and in vivo biological properties were
      characterized. Given the high immunogenicity and good propagation characteristics
      of the CTNCEC25 strain, it has excellent potential to be a candidate for
      development into a human rabies vaccine with high safety and quality
      characteristics for controlling rabies in China.

PMID- 24885667
TI  - The effect of hormonal estrus induction on maternal effect and apoptosis-related
      genes expression in porcine cumulus-oocyte complexes.
AB  - BACKGROUND: The effect of hormonal estrus induction on maternal effect (MATER -
      maternal antigen that embryo requires, ZAR-1 - zygote arrest 1, and BMP15 - bone
      morphogenetic protein 15) and apoptosis-related genes expression (BCL-2 and BAX)
      in porcine cumulus-oocyte complexes (COCs) and selected follicular parameters was
      investigated in this study. METHODS: Gilts were divided into three groups: (I)
      with natural estrus; (II) stimulated with PMSG/hCG; and (III) with PMSG/hCG +
      PGF2alpha. Analysis of maternal effect and apoptosis-related transcripts
      expression in COCs, and progesterone synthesis pathway genes expression (P450scc
      and 3betaHSD) in granulosa cells was performed by qPCR. BMP15 protein expression
      in follicular fluid (FF) was analyzed by western blot. Oocyte nuclear maturation
      was assessed by aceto-orcein staining. Progesterone (P4) and estradiol (E2)
      concentrations in FF and serum were measured by ELISA. Data were analyzed with
      the one-way ANOVA and Bonferroni post-test or Kruskal-Wallis test and Dunns post
      test. RESULTS: The highest expression of MATER, ZAR-1, and BMP15 genes was found
      in COCs recovered from gilts treated with PMSG/hCG when compared to PMSG/hCG +
      PGF2alpha-stimulated or non-stimulated gilts. Hormonal treatment did not affect
      the BMP15 protein expression in FF, but increased the expression of genes
      participating in P4 synthesis in granulosa cells. The higher percentage of
      immature oocytes was found in PMSG/hCG-treated when compared to the non
      stimulated gilts. The expression of BCL-2 and BAX mRNA, and BCL-2/BAX mRNA ratio
      was significantly higher in COCs derived from PMSG/hCG-treated when compared to
      PMSG/hCG + PGF2alpha-treated or non-stimulated subjects. The level of P4 in serum
      was similar in animals from all experimental groups, while its concentration in
      FF was greater in gilts subjected to PMSG/hCG treatment than in PMSG/hCG +
      PGF2alpha-stimulated and non-stimulated gilts. The concentration of E2 did not
      differ in the serum or FF between the control group and the hormonally stimulated
      groups. CONCLUSIONS: Hormonal induction of estrus affected maternal effect gene
      transcripts levels in COCs and and oocyte nuclear maturation. The inclusion of
      PGF2alpha into the stimulation protocol enabled maintaining of physiological
      concentration of P4 in FF. Additionally, both hormonal treatments seem to be
      beneficial for apoptosis prevention through increasing BCL-2/BAX transcript
      ratio.

PMID- 24885668
TI  - Individual experience affects host choice in malaria vector mosquitoes.
AB  - BACKGROUND: Despite epidemiological importance, few studies have explored whether
      individual experience and learning could affect the vertebrate host choice of
      mosquito disease vectors. Here, we investigated whether a first successful blood
      meal can modulate mosquito preference during a second blood meal. METHODS: In no
      choice situations, females of the mosquito Anopheles coluzzii, one of the primary
      African malaria vectors, were first allowed to feed on either human, rabbit or
      guinea pig. Four days later in dual-choice situations, the same mosquitoes were
      allowed to choose between the two uncommon hosts, rabbit and guinea pig, as a
      source of blood. ELISA assays were then used to determine which host mosquitoes
      fed on. RESULTS: Our results indicate that, overall, mosquitoes preferred to feed
      on rabbit over guinea pig and that the nature of the first blood meal had a
      significant impact on the mosquito host choice during the second blood meal.
      Compared to mosquitoes that previously fed on guinea pigs or humans, mosquitoes
      that fed on rabbits were less likely to choose this host species during a second
      exposition. The decreased preference for rabbit was observed four days after
      mosquitoes were first exposed to this host, suggesting that the effect lasts at
      least the duration of a gonotrophic cycle. Furthermore, this effect was observed
      after only one successful blood meal. Fitness measurements on mosquitoes fed on
      the three different vertebrate hosts showed that the origin of the blood meal
      affected mosquito longevity but not fecundity. In particular, human-fed
      mosquitoes lived longer than guinea pig-fed or rabbit-fed mosquitoes.
      CONCLUSIONS: Our study demonstrates that individual experience affects host
      choice in this mosquito species and might have strong repercussions on biting
      patterns in natural conditions and hence on malaria transmission.

PMID- 24885669
TI  - Integration of robotic surgery into routine practice and impacts on
      communication, collaboration, and decision making: a realist process evaluation
      protocol.
AB  - BACKGROUND: Robotic surgery offers many potential benefits for patients. While an
      increasing number of healthcare providers are purchasing surgical robots, there
      are reports that the technology is failing to be introduced into routine
      practice. Additionally, in robotic surgery, the surgeon is physically separated
      from the patient and the rest of the team, with the potential to negatively
      impact teamwork in the operating theatre. The aim of this study is to ascertain:
      how and under what circumstances robotic surgery is effectively introduced into
      routine practice; and how and under what circumstances robotic surgery impacts
      teamwork, communication and decision making, and subsequent patient outcomes.
      METHODS AND DESIGN: We will undertake a process evaluation alongside a randomised
      controlled trial comparing laparoscopic and robotic surgery for the curative
      treatment of rectal cancer. Realist evaluation provides an overall framework for
      the study. The study will be in three phases. In Phase I, grey literature will be
      reviewed to identify stakeholders' theories concerning how robotic surgery
      becomes embedded into surgical practice and its impacts. These theories will be
      refined and added to through interviews conducted across English hospitals that
      are using robotic surgery for rectal cancer resection with staff at different
      levels of the organisation, along with a review of documentation associated with
      the introduction of robotic surgery. In Phase II, a multi-site case study will be
      conducted across four English hospitals to test and refine the candidate
      theories. Data will be collected using multiple methods: the structured
      observation tool OTAS (Observational Teamwork Assessment for Surgery); video
      recordings of operations; ethnographic observation; and interviews. In Phase III,
      interviews will be conducted at the four case sites with staff representing a
      range of surgical disciplines, to assess the extent to which the results of Phase
      II are generalisable and to refine the resulting theories to reflect the
      experience of a broader range of surgical disciplines. The study will provide (i)
      guidance to healthcare organisations on factors likely to facilitate successful
      implementation and integration of robotic surgery, and (ii) guidance on how to
      ensure effective communication and teamwork when undertaking robotic surgery.

PMID- 24885670
TI  - Updates on clinical studies of selenium supplementation in radiotherapy.
AB  - To establish guidelines for the selenium supplementation in radiotherapy we
      assessed the benefits and risks of selenium supplementation in radiotherapy.
      Clinical studies on the use of selenium in radiotherapy were searched in the
      PubMed electronic database in January 2013. Sixteen clinical studies were
      identified among the 167 articles selected in the initial search. Ten articles
      were observational studies, and the other 6 articles reported studies on the
      effects of selenium supplementation in patients with cancer who underwent
      radiotherapy. The studies were conducted worldwide including European, American
      and Asian countries between 1987 and 2012. Plasma, serum or whole blood selenium
      levels were common parameters used to assess the effects of radiotherapy and the
      selenium supplementation status. Selenium supplementation improved the general
      conditions of the patients, improved their quality of life and reduced the side
      effects of radiotherapy. At the dose of selenium used in these studies (200-500
      MUg/day), selenium supplementation did not reduce the effectiveness of
      radiotherapy, and no toxicities were reported. Selenium supplementation may offer
      specific benefits for several types of cancer patients who undergo radiotherapy.
      Because high-dose selenium and long-term supplementation may be unsafe due to
      selenium toxicity, more evidence-based information and additional research are
      needed to ensure the therapeutic benefits of selenium supplementation.

PMID- 24885672
TI  - Comparison of conventional medicine, TCM treatment, and combination of both
      conventional medicine and TCM treatment for patients with chronic obstructive
      pulmonary disease: study protocol of a randomized comparative effectiveness
      research trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects millions
      worldwide. Although many therapies exist and are being developed to relieve
      symptoms and reduce mortality, few data are available to understand which of the
      therapeutic alternatives is the most cost-effective for COPD patients in everyday
      clinical practice, especially for traditional Chinese medicine (TCM). Comparative
      effectiveness research can help patients, clinicians, and decision-makers make
      best informed treatment decisions where such evidence was previously lacking.
      This study aims to compare the effectiveness and economic evaluation of three
      treatments: (1) conventional Western medicine; (2) TCM treatments, which have
      been evaluated and have certain effect; and (3) a combination of both
      conventional Western medicine and TCM treatments, and then determine which
      treatment is the most suitable for COPD patients. METHODS/DESIGN: A multicenter,
      pragmatic, randomized, controlled trial is adopted. A total of 360 patients will
      be recruited and randomly assigned to one of the three treatments group, with 120
      in each group. Patients in the conventional Western medicine group will be given
      Salbutamol, Formoterol, Salmeterol/fluticasone, respectively, according to the
      guidelines. For the TCM group, patients will be given Bufei granule, Bu-Fei Jian
      Pi granule, Bu-Fei Yi-Shen granule, and Yi-Qi Zi-Shen granule based on their
      corresponding TCM syndrome patterns, respectively. For the combination of
      conventional medicine and TCM treatments group, patients will be given a
      combination of conventional Western medicine and TCM granules. Treatments in each
      group are recognized as a whole comprehensive intervention. After the 26-week
      treatment, another 26 weeks will be followed up. The outcome measures including
      the frequency and duration of acute exacerbations, lung function, dyspnea,
      exercise capacity, quality of life, and economic evaluation will be assessed.
      DISCUSSION: It is hypothesized that each of the three treatments will have
      beneficial effects in reducing the frequency and duration of acute exacerbations,
      improving exercise capacity and psychosocial function of COPD patients. In
      addition, the combination of conventional medicine and TCM treatments may be most
      suitable for COPD patients with better effectiveness and economic evaluation.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01836016.

PMID- 24885671
TI  - Induction of stem-like cells with malignant properties by chronic exposure of
      human lung epithelial cells to single-walled carbon nanotubes.
AB  - BACKGROUND: Carbon nanotubes (CNT) hold great promise to create new and better
      products for commercial and biomedical applications, but their long-term adverse
      health effects are a major concern. The objective of this study was to address
      human lung cancer risks associated with chronic pulmonary exposure to single
      walled (SW) CNT through the fundamental understanding of cellular and molecular
      processes leading to carcinogenesis. We hypothesized that the acquisition of
      cancer stem cells (CSC), a subpopulation that drive tumor initiation and
      progression, may contribute to CNT carcinogenesis. METHODS: Non-tumorigenic human
      lung epithelial cells were chronically exposed to well-dispersed SWCNT for a
      period of 6 months at the physiologically relevant concentration of 0.02 MUg/cm2
      surface area dose. Chronic SWCNT-exposed cells were evaluated for the presence of
      CSC-like cells under CSC-selective conditions of tumor spheres and side
      population (SP). CSC-like cells were isolated using fluorescence-activated cell
      sorting and were assessed for aggressive behaviors, including acquired apoptosis
      resistance and increased cell migration and invasion in vitro, and tumor
      initiating capability in vivo. Non-small cell lung cancer cells served as a
      positive control. RESULTS: We demonstrated for the first time the existence of
      CSC-like cells in all clones of chronic SWCNT-exposed lung epithelial cells.
      These CSC-like cells, in contrary to their non-CSC counterpart, possessed all
      biological features of lung CSC that are central to irreversible malignant
      transformation, self-renewal, aggressive cancer behaviors, and in vivo
      tumorigenesis. These cells also displayed aberrant stem cell markers, notably
      Nanog, SOX-2, SOX-17 and E-cadherin. Restored expression of tumor suppressor p53
      abrogated CSC properties of CSC-like cells. Furthermore, we identified specific
      stem cell surface markers CD24low and CD133high that are associated with SWCNT
      induced CSC formation and tumorigenesis. CONCLUSIONS: Our findings provide new
      and compelling evidence for the acquisition of CSC-like cells induced by chronic
      SWCNT exposure, which are likely to be a major driving force for SWCNT
      tumorigenesis. Thus, our study supports prudent adoption of prevention strategies
      and implementation of exposure control for SWCNT. We also suggest that the
      detection of CSC and associated surface markers may provide an effective
      screening tool for prediction of the carcinogenic potential of SWCNT and related
      nanoparticles.

PMID- 24885673
TI  - Effectiveness of the Dader Method for pharmaceutical care in patients with
      bipolar I disorder: EMDADER-TAB: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Bipolar I disorder (BD-I) is a chronic mental illness characterized
      by the presence of one or more manic episodes, or both depressive and manic
      episodes, usually separated by asymptomatic intervals. Pharmacists can contribute
      to the management of BD-I, mainly with the use of effective and safe drugs, and
      improve the patient's life quality through pharmaceutical care. Some studies have
      shown the effect of pharmaceutical care in the achievement of therapeutic goals
      in different illnesses; however, to our knowledge, there is a lack of randomized
      controlled trials designed to assess the effect of pharmacist intervention in
      patients with BD. The aim of this study is to assess the effectiveness of the
      Dader Method for pharmaceutical care in patients with BD-I. METHODS/DESIGN:
      Randomized, controlled, prospective, single-center clinical trial with duration
      of 12 months will be performed to compare the effect of Dader Method of
      pharmaceutical care with the usual care process of patients in a psychiatric
      clinic. Patients diagnosed with BD-I aged between 18 and 65 years who have been
      discharged or referred from outpatients service of the San Juan de Dios Clinic
      (Antioquia, Colombia) will be included. Patients will be randomized into the
      intervention group who will receive pharmaceutical care provided by pharmacists
      working in collaboration with psychiatrists, or into the control group who will
      receive usual care and verbal-written counseling regarding BD. Study outcomes
      will be assessed at baseline and at 3, 6, 9, and 12 months after randomization.
      The primary outcome will be to measure the number of hospitalizations, emergency
      service consultations, and unscheduled outpatient visits. Effectiveness, safety,
      adherence, and quality of life will be assessed as secondary outcomes.
      Statistical analyses will be performed using two-tailed McNemar tests, Pearson
      chi-square tests, and Student's t-tests; a P value <0.05 will be considered as
      statistically significant. DISCUSSION: As far as we know, this is the first
      randomized controlled trial to assess the effect of the Dader Method for
      pharmaceutical care in patients with BD-I and it could generate valuable
      information and recommendations about the role of pharmacists in the improvement
      of therapeutic goals, solution of drug-related problems, and adherence. TRIAL
      REGISTRATION: Registration number NCT01750255 on August 6, 2012. First patient
      randomized on 24 November 2011.

PMID- 24885674
TI  - The development of a comprehensive multidisciplinary care pathway for patients
      with a hip fracture: design and results of a clinical trial.
AB  - BACKGROUND: Hip fractures frequently occur in older persons and severely decrease
      life expectancy and independence. Several care pathways have been developed to
      lower the risk of negative outcomes but most pathways are limited to only one
      aspect of care. The aim of this study was therefore to develop a comprehensive
      care pathway for older persons with a hip fracture and to conduct a preliminary
      analysis of its effect. METHODS: A comprehensive multidisciplinary care pathway
      for patients aged 60 years or older with a hip fracture was developed by a
      multidisciplinary team. The new care pathway was evaluated in a clinical trial
      with historical controls. The data of the intervention group were collected
      prospectively. The intervention group included all patients with a hip fracture
      who were admitted to University Medical Center Groningen between 1 July 2009 and
      1 July 2011. The data of the control group were collected retrospectively. The
      control group comprised all patients with a hip fracture who were admitted
      between 1 January 2006 and 1 January 2008. The groups were compared with the
      independent sample t-test, the Mann-Whitney U-test or the Chi-squared test (Phi
      test). The effect of the intervention on fasting time and length of stay was
      adjusted by linear regression analysis for differences between the intervention
      and control group. RESULTS: The intervention group included 256 persons (women,
      68%; mean age (SD), 78 (9) years) and the control group 145 persons (women, 72%;
      mean age (SD), 80 (10) years). Median preoperative fasting time and median length
      of hospital stay were significantly lower in the intervention group: 9 vs. 17
      hours (p < 0.001), and 7 vs. 11 days (p < 0.001), respectively. A similar result
      was found after adjustment for age, gender, living condition and American Society
      of Anesthesiologists (ASA) classification. In-hospital mortality was also lower
      in the intervention group: 2% vs. 6% (p < 0.05). There were no statistically
      significant differences in other outcome measures. CONCLUSIONS: The new
      comprehensive care pathway was associated with a significant decrease in
      preoperative fasting time and length of hospital stay.

PMID- 24885676
TI  - Nutrition education and leadership for improved clinical outcomes: training and
      supporting junior doctors to run 'Nutrition Awareness Weeks' in three NHS
      hospitals across England.
AB  - BACKGROUND: One in four adults are estimated to be at medium to high risk of
      malnutrition when screened using the 'Malnutrition Universal Screening Tool' upon
      admission to hospital in the United Kingdom. The Need for Nutrition
      Education/Education Programme (NNEdPro) Group was developed to address this issue
      and the Nutrition Education and Leadership for Improved Clinical Outcomes
      (NELICO) is a project within this group.The objective of NELICO was to assess
      whether an intensive training intervention combining clinical and public health
      nutrition, organisational management and leadership strategies, could equip
      junior doctors to contribute to improvement in nutrition awareness among
      healthcare professionals in the National Health Service in England. METHODS:
      Three junior doctors were self-selected from the NNEdPro Group original training.
      Each junior doctor recruited three additional team members to attend an intensive
      training weekend incorporating nutrition, change management and leadership. This
      equipped them to run nutrition awareness weeks in their respective hospitals.
      Knowledge, attitudes and practices were evaluated at baseline as well as one and
      four months post-training as a quality assurance measure. The number and type of
      educational events held, pre-awareness week Online Hospital Survey results,
      attendance and qualitative feedback from training sessions, effectiveness of
      dissemination methods such as awareness stalls, Hospital Nutrition Attitude
      Survey results and overall feedback were also used to determine impact. RESULTS:
      When the weighted average score for knowledge, attitudes and practices at
      baseline was compared with four months post-intervention scores, there was a
      significant increase in the overall score (p = 0.03). All three hospital teams
      conducted an effective nutrition awareness week, as determined by qualitative
      data collected from interviews and feedback from educational sessions.
      CONCLUSION: The NELICO project and its resulting nutrition awareness weeks were
      considered innovative in terms of concept and content. It was considered useful,
      both for the junior doctors who showed improvement in their nutrition knowledge
      and reported enthusiasm and for the hospital setting, increasing awareness of
      clinical and public health nutrition among healthcare professionals. The NELICO
      project is one innovative method to promote nutrition awareness in tomorrow's
      doctors and shows they have the enthusiasm and drive to be nutrition champions.

PMID- 24885675
TI  - Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and
      modulatory determinants of Wnt signaling activity.
AB  - BACKGROUND: Wnt proteins are a family of secreted signaling molecules that
      regulate key developmental processes in metazoans. The molecular basis of Wnt
      binding to Frizzled and LRP5/6 co-receptors has long been unknown due to the lack
      of structural data on Wnt ligands. Only recently, the crystal structure of the
      Wnt8-Frizzled8-cysteine-rich-domain (CRD) complex was solved, but the
      significance of interaction sites that influence Wnt signaling has not been
      assessed. RESULTS: Here, we present an extensive structure-function analysis of
      mouse Wnt3a in vitro and in vivo. We provide evidence for the essential role of
      serine 209, glycine 210 (site 1) and tryptophan 333 (site 2) in Fz binding.
      Importantly, we discovered that valine 337 in the site 2 binding loop is critical
      for signaling without contributing to binding. Mutations in the presumptive
      second CRD binding site (site 3) partly abolished Wnt binding. Intriguingly, most
      site 3 mutations increased Wnt signaling, probably by inhibiting Wnt-CRD
      oligomerization. In accordance, increasing amounts of soluble Frizzled8-CRD
      protein modulated Wnt3a signaling in a biphasic manner. CONCLUSIONS: We propose a
      concentration-dependent switch in Wnt-CRD complex formation from an inactive
      aggregation state to an activated high mobility state as a possible modulatory
      mechanism in Wnt signaling gradients.

PMID- 24885677
TI  - Giant aneurysm of distal posterior inferior cerebellar artery: a case report and
      review of the literature.
AB  - INTRODUCTION: Aneurysms in the vertebrobasilar system are rare and in the distal
      segment of the posterior inferior cerebellar artery they are even less frequent.
      Giant aneurysms are also rare in the posterior cranial fossa. Giant aneurysms of
      the distal posterior inferior cerebellar artery generally can have mainly
      compressive effects on the adjacent structures and they can be mistaken for
      tumors. CASE PRESENTATION: We report the case of a 74-year-old Italian woman who
      presented with a complaint of dizziness. Her dizziness was found to be a result
      of aneurysmal dilatation arising from the distal segment of the right posterior
      inferior cerebellar artery. A mid-line suboccipital craniotomy was performed, and
      the aneurysm was clipped without post-operative deficits and with improvement in
      the patient's dizziness. In our present report, we also review the literature and
      discuss our case with regard to the clinical and radiological features and
      surgical procedure performed. CONCLUSION: To the best of our knowledge, few cases
      of this type of aneurysm have been described in the literature. Our patient had a
      good outcome after surgical treatment.

PMID- 24885678
TI  - In-office diagnostic arthroscopy for knee and shoulder intra-articular injuries
      its potential impact on cost savings in the United States.
AB  - BACKGROUND: The purpose of this analysis was to determine whether in office
      diagnostic needle arthroscopy (Visionscope Imaging System [VSI]) can provide for
      improved diagnostic assessment and; more cost effective care. METHODS: Data on
      arthroscopy procedures in the US for deep seated pathology in the knee and
      shoulder were used (Calendar Year 2012). These procedures represent approximately
      25-30% of all arthroscopic procedures performed annually. Sensitivities,
      specificities, positive predictive, and negative predictive values for MRI
      analysis of this deep seated pathology from systematic reviews and meta-analyses
      were used in assessing for false positive and false negative MRI findings. The
      costs of performing diagnostic and surgical arthroscopy procedures (using 2013
      Medicare reimbursement amounts); costs associated with false negative findings;
      and the costs for treating associated complications arising from diagnostic and
      therapeutic arthroscopy procedures were then assessed. RESULTS: In patients
      presenting with medial meniscal pathology (ICD9CM diagnosis 836.0 over 540,000
      procedures in CY 2012); use of the VSI system in place of MRI assessment
      (standard of care) resulted in a net cost savings to the system of $151 million.
      In patients presenting with rotator cuff pathology (ICD9CM 840.4 over 165,000
      procedures in CY2012); use of VSI in place of MRI similarly saved $59 million.
      These savings were realized along with more appropriate care as; fewer patients
      were exposed to higher risk surgical arthroscopic procedures. CONCLUSIONS: The
      use of an in-office arthroscopy system can: possibly save the US healthcare
      system money; shorten the diagnostic odyssey for patients; potentially better
      prepare clinicians for arthroscopic surgery (when needed) and; eliminate
      unnecessary outpatient arthroscopy procedures, which commonly result in surgical
      intervention.

PMID- 24885679
TI  - Hyper-heuristic Evolution of Dispatching Rules: A Comparison of Rule
      Representations.
AB  - Dispatching rules are frequently used for real-time, online scheduling in complex
      manufacturing systems. Design of such rules is usually done by experts in a time
      consuming trial-and-error process. Recently, evolutionary algorithms have been
      proposed to automate the design process. There are several possibilities to
      represent rules for this hyper-heuristic search. Because the representation
      determines the search neighborhood and the complexity of the rules that can be
      evolved, a suitable choice of representation is key for a successful evolutionary
      algorithm. In this paper we empirically compare three different representations,
      both numeric and symbolic, for automated rule design: A linear combination of
      attributes, a representation based on artificial neural networks, and a tree
      representation. Using appropriate evolutionary algorithms (CMA-ES for the neural
      network and linear representations, genetic programming for the tree
      representation), we empirically investigate the suitability of each
      representation in a dynamic stochastic job shop scenario. We also examine the
      robustness of the evolved dispatching rules against variations in the underlying
      job shop scenario, and visualize what the rules do, in order to get an intuitive
      understanding of their inner workings. Results indicate that the tree
      representation using an improved version of genetic programming gives the best
      results if many candidate rules can be evaluated, closely followed by the neural
      network representation that already leads to good results for small to moderate
      computational budgets. The linear representation is found to be competitive only
      for extremely small computational budgets. 

PMID- 24885680
TI  - Fitness Probability Distribution of Bit-Flip Mutation.
AB  - Bit-flip mutation is a common mutation operator for evolutionary algorithms
      applied to optimize functions over binary strings. In this paper, we develop
      results from the theory of landscapes and Krawtchouk polynomials to exactly
      compute the probability distribution of fitness values of a binary string
      undergoing uniform bit-flip mutation. We prove that this probability distribution
      can be expressed as a polynomial in p, the probability of flipping each bit. We
      analyze these polynomials and provide closed-form expressions for an easy linear
      problem (Onemax), and an NP-hard problem, MAX-SAT. We also discuss a connection
      of the results with runtime analysis. 

PMID- 24885681
TI  - Paraneoplastic granulocyte colony-stimulating factor secretion in soft tissue
      sarcoma mimicking myeloproliferative neoplasia: a case report.
AB  - BACKGROUND: While paraneoplastic leukocytosis is a common phenomenon in solid
      tumors, extreme elevations of white blood counts (WBC) in the range of more than
      100,000/MUl are uncommon in patients with non-hematologic malignancies.
      Leukocytosis with mature neutrophils due to a granulocyte colony-stimulating
      factor (G-CSF) producing tumor is only seen on rare occasions. CASE PRESENTATION:
      Massive neutrophil leukocytosis of approximately 100,000/MUl was diagnosed in a
      57-year-old Caucasian woman with metastatic undifferentiated endometrial sarcoma.
      A bone marrow trephine biopsy revealed massively increased granulopoiesis, but no
      evidence of monoclonal myeloproliferative disease. After the primary tumor had
      been resected, white blood count (WBC) plummeted and went back to nearly normal
      levels within one week. With progressive metastatic disease, granulocyte colony
      stimulating factor (G-CSF) plasma levels were found to be increased by 10-fold.
      White blood count (WBC) strictly correlated with tumor burden and response to
      chemotherapy. In the final stage of treatment resistent disease, white blood
      count (WBC) approximated 300,000/MUl. CONCLUSION: We report on a granulocyte
      colony-stimulating factor (G-CSF) secreting undifferentiated endometrial sarcoma,
      which was associated with extreme neutrophil counts. White blood count (WBC) were
      closely correlated with tumor burden and associated with an aggressive clinical
      course. We suggest that paraneoplastic neutrophilia represents a poor prognostic
      sign in soft tissue sarcoma. In patients with similar constellations, antitumor
      therapy must not be delayed.

PMID- 24885682
TI  - Assessing the antibiotic potential of essential oils against Haemophilus ducreyi.
AB  - BACKGROUND: Haemophilus ducreyi is the bacterium responsible for the genital
      ulcer disease chancroid, a cofactor for the transmission of HIV, and it is
      resistant to many antibiotics. With the goal of exploring possible alternative
      treatments, we tested essential oils (EOs) for their efficacy as antimicrobial
      agents against H. ducreyi. METHODS: We determine the minimum inhibitory
      concentration (MIC) of Cinnamomum verum (cinnamon), Eugenia caryophyllus (clove)
      and Thymus satureioides (thyme) oil against 9 strains of H. ducreyi using the
      agar dilution method. We also determined the minimum lethal concentration for
      each oil by subculturing from the MIC plates onto fresh agar without essential
      oil. For both tests, we used a 2-way ANOVA to evaluate whether antibiotic
      resistant strains had a different sensitivity to the oils relative to non
      resistant strains. RESULTS: All 3 oils demonstrated excellent activity against H.
      ducreyi, with MICs of 0.05 to 0.52 mg/mL and MLCs of 0.1-0.5 mg/mL. Antibiotic
      resistant strains of H. ducreyi were equally susceptible to these 3 essential
      oils relative to non-resistant strains (p=0.409). CONCLUSION: E. caryophyllus, C.
      verum and T. satureioides oils are promising alternatives to antibiotic treatment
      for chancroid.

PMID- 24885683
TI  - Burnout and daily recovery: a day reconstruction study.
AB  - What can employees who are at risk of burnout do in their off-job time to recover
      adequately from their work? Extending the effort-recovery theory, we hypothesize
      that the continuation of work during off-job time results in lower daily
      recovery, whereas engagement in 'nonwork' activities (low-effort, social, and
      physical activities) results in higher daily recovery for employees who are at
      risk of burnout versus employees with low levels of burnout. A day reconstruction
      method was used to assess daily time spent on off-job activities after work, and
      daily recovery levels (i.e., physical vigor, cognitive liveliness, and recovery).
      In total, 287 employees filled in a general questionnaire to assess general
      levels of burnout. Thereafter, participants were asked to reconstruct their off
      job time use and state recovery levels during 2 workweeks, resulting in a total
      of 2,122 workdays. Results of multilevel modeling supported all hypotheses,
      except the hypothesis regarding off-job time spent on physical activities. The
      findings contribute to the literature by showing that employees who are at risk
      of burnout should stop working and start spending time on nonwork activities to
      adequately recover from work on a daily basis.

PMID- 24885684
TI  - Embeddedness and well-being in the United States and Singapore: the mediating
      effects of work-to-family and family-to-work conflict.
AB  - Guided by conservation of resources theory, we propose that both organizational
      and community embeddedness are associated with increased work-to-family conflict
      (WFC) and family to-work conflict (FWC), which in turn are associated with strain
      related outcomes. Because stress can have both short-term and long-term
      consequences, we examined negative mood as an immediate reaction to stress and
      chronic insomnia as a longer-term reaction to stress. We examined these
      relationships in 2-career couples in both the United States (n = 416) and
      Singapore (n = 400). Results provided full support for the mediating effects of
      WFC and FWC in the U.S. sample, with only limited support for those mediating
      effects in the Singaporean sample. In addition, we found that the effects of
      community embeddedness on FWC were significantly stronger in the U.S. sample than
      in the Singaporean sample.

PMID- 24885685
TI  - Time pressure and coworker support mediate the curvilinear relationship between
      age and occupational well-being.
AB  - As the proportion of older employees in the workforce is growing, researchers
      have become increasingly interested in the association between age and
      occupational well-being. The curvilinear nature of relationships between age and
      job satisfaction and between age and emotional exhaustion is well-established in
      the literature, with employees in their late 20s to early 40s generally reporting
      lower levels of occupational well-being than younger and older employees.
      However, the mechanisms underlying these curvilinear relationships are so far not
      well understood due to a lack of studies testing mediation effects. Based on an
      integration of role theory and research from the adult development and career
      literatures, this study examined time pressure, work-home conflict, and coworker
      support as mediators of the relationships between age and job satisfaction and
      between age and emotional exhaustion. Data came from 771 employees between 17 and
      74 years of age in the construction industry. Results showed that employees in
      their late 20s to early 40s had lower job satisfaction and higher emotional
      exhaustion than younger and older employees. Time pressure and coworker support
      fully mediated both the U-shaped relationship between age and job satisfaction
      and the inversely U-shaped relationship between age and emotional exhaustion.
      These findings suggest that organizational interventions may help increase the
      relatively low levels of occupational well-being in certain age groups.

PMID- 24885686
TI  - Boredom at work: proximal and distal consequences of affective work-related
      boredom.
AB  - Boredom is an emotion that occurs regularly at the workplace, with negative
      consequences for the employee and the organization. It is therefore important to
      understand why work-related boredom leads to such adverse consequences and what
      can be done to mitigate its occurrence and its negative consequences. In the
      present study we proposed a model suggesting that feelings of boredom at work
      induce immediate affect-based bored behaviors, and that such bored behavior leads
      to depressive complaints, distress, and counterproductive work behavior. We
      further posed that job crafting can mitigate work-related boredom and its
      negative outcomes. Results of a survey study among 189 employees showed that work
      related boredom and bored behavior are empirically distinct, though related,
      constructs. Work-related boredom was positively related to depressive complaints,
      distress, and counterproductive work behavior, and these associations were fully
      mediated by bored behavior. Job crafting related negatively to work-related
      boredom, and attenuated the relationship of work-related boredom with bored
      behavior. Moreover, the indirect effects of work-related boredom through bored
      behavior on its outcomes were smaller the more employees engaged in job crafting.
      This research enhances insight into work-related boredom by showing that boredom
      as an affective state can be distinguished from its proximal behavioral
      consequences, and by providing a first onset to obtain insight in moderating and
      mediating mechanisms that may explain work-related boredom's consequences. It
      highlights the importance of employees' opportunities to work in jobs that do not
      cause work-related boredom to develop, and the role of job crafting as a
      potential intervention tool.

PMID- 24885687
TI  - Workplace mistreatment climate and potential employee and organizational
      outcomes: a meta-analytic review from the target's perspective.
AB  - This meta-analytic study summarizes relations between workplace mistreatment
      climate-MC (specific to incivility, aggression, and bullying) and potential
      outcomes. We define MC as individual or shared perceptions of organizational
      policies, procedures, and practices that deter interpersonal mistreatment. We
      located 35 studies reporting results with individual perceptions of MC
      (psychological MC) that yielded 36 independent samples comprising 91,950
      employees. Through our meta-analyses, we found significant mean correlations
      between psychological MC and employee and organizational outcomes including
      mistreatment reduction effort (motivation and performance), mistreatment
      exposure, strains, and job attitudes. Moderator analyses revealed that the
      psychological MC-outcome relations were generally stronger for perceived civility
      climate than for perceived aggression-inhibition climate, and content
      contamination of existing climate scales accentuated the magnitude of the
      relations between psychological MC and some outcomes (mistreatment exposure and
      employee strains). Further, the magnitudes of the psychological MC-outcome
      relations were generally comparable across studies using dominant (i.e., most
      commonly used) and other climate scales, but for some focal relations, magnitudes
      varied with respect to cross-sectional versus prospective designs. The 4 studies
      that assessed MC at the unit-level had results largely consistent with those at
      the employee level.

PMID- 24885688
TI  - Work-family conflict among members of full-time dual-earner couples: an
      examination of family life stage, gender, and age.
AB  - Based on cross-sectional data from the 2008 National Study of the Changing
      Workforce, this study investigates relationships between gender, age, and work
      family conflict across 6 family life stages. Participants were 690
      married/partnered employees who worked 35 or more hours a week. Results indicated
      a small but negative relationship between age and work-family conflict. Work
      family conflict was also associated with family stage, with the least amount of
      conflict occurring during the empty nest stage and the most occurring when the
      youngest child in the home was 5 years of age or younger. Gender differences were
      also observed. Specifically, men reported more work interference with family than
      did women when the youngest child in the home was a teen. Women overall reported
      more family interference with work than did men. Results concerning age and
      gender revealed a different pattern demonstrating that family stage is not simply
      a proxy for age. Age had a main effect on work-to-family conflict that was
      monotonic in nature and on family to-work conflict that was linear in nature. In
      conclusion, the results indicate gender, age, and family stage each uniquely
      relate to work-family conflict.

PMID- 24885689
TI  - Delivery, immediate newborn and cord care practices in Pemba Tanzania: a
      qualitative study of community, hospital staff and community level care providers
      for knowledge, attitudes, belief systems and practices.
AB  - BACKGROUND: Deaths during the neonatal period account for almost two-thirds of
      all deaths in the first year of life and 40 percent of deaths before the age of
      five. Most of these deaths could be prevented through proven cost-effective
      interventions. Although there are some recent data from sub-Saharan Africa, but
      there is paucity of qualitative data from Zanzibar and cord care practices data
      from most of East Africa. We undertook a qualitative study in Pemba Island as a
      pilot to explore the attitudes, beliefs and practices of the community and health
      workers related to delivery, newborn and cord care with the potential to inform
      the main chlorhexidine (CHX) trial. METHODS: 80 in-depth interviews (IDI) and 11
      focus group discussions (FGD) involving mothers, grandmothers, fathers,
      traditional birth attendants and other health service providers from the
      community were undertaken. All IDIs and FGDs were audio taped, transcribed and
      analyzed using ATLAS ti 6.2. RESULTS: Poor transportation, cost of delivery at
      hospitals, overcrowding and ill treatment by hospital staff are some of the
      obstacles for achieving higher institutional delivery. TBAs and health
      professionals understand the need of using sterilized equipments to reduce risk
      of infection to both mothers and their babies during delivery. Despite this
      knowledge, use of gloves during delivery and hand washing before delivery were
      seldom reported. Early initiation of breastfeeding and feeding colostrum was
      almost universal. Hospital personnel and trained TBAs understood the importance
      of keeping babies warm after birth and delayed baby's first bath. The importance
      of cord care was well recognized in the community. Nearly all TBAs counseled the
      mothers to protect the cord from dust, flies and mosquitoes or any other kind of
      infections by covering it with cloth. There was consensus among respondents that
      CHX liquid cord cleansing could be successfully implemented in the community with
      appropriate education and awareness. CONCLUSION: The willingness of community in
      accepting a CHX cord care practice was very high; the only requirement was that a
      MCH worker needs to do and demonstrate the use to the mother. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01528852.

PMID- 24885691
TI  - South Africa's protracted struggle for equal distribution and equitable access -
      still not there.
AB  - The purpose of this contribution is to analyse and explain the South African HRH
      case, its historical evolution, and post-apartheid reform initiatives aimed at
      addressing deficiencies and shortfalls. HRH in South Africa not only mirrors the
      nature and diversity of challenges globally, but also the strategies pursued by
      countries to address these challenges. Although South Africa has strongly
      developed health professions, large numbers of professional and mid-level
      workers, and also well-established training institutions, it is experiencing
      serious workforce shortages and access constraints. This results from the unequal
      distribution of health workers between the well-resourced private sector over the
      poorly-resourced public sector, as well as from distributional disparities
      between urban and rural areas. During colonial and apartheid times, disparities
      were aggravated by policies of racial segregation and exclusion, remnants of
      which are today still visible in health-professional backlogs, unequal provincial
      HRH distribution, and differential access to health services for specific race
      and class groups. Since 1994, South Africa's transition to democracy deeply
      transformed the health system, health professions and HRH establishments. The
      introduction of free-health policies, the district health system and the
      prioritisation of PHC ensured more equal distribution of the workforce, as well
      as greater access to services for deprived groups. However, the HIV/AIDS epidemic
      brought about huge demands for care and massive patient loads in the public
      sector. The emigration of health professionals to developed countries and to the
      private sector also undermines the strength and effectiveness of the public
      health sector. For the poor, access to care thus remains constrained and in
      perpetual shortfall. The post-1994 government has introduced several HRH-specific
      strategies to recruit, distribute, motivate and retain health professionals to
      strengthen the public sector and to expand access and coverage. Of great
      significance among these is the NHI Plan that aims to bridge the structural
      divide and to redistribute material and human resources more equally. Its success
      largely hinges on HRH and the balanced deployment of the national workforce.Low-
      and middle-income countries have much to learn from South African HRH
      experiences. In turn, South Africa has much to learn from other countries, as
      this case study shows.

PMID- 24885690
TI  - Genetic targeting of B-RafV600E affects survival and proliferation and identifies
      selective agents against BRAF-mutant colorectal cancer cells.
AB  - BACKGROUND: Colorectal cancers carrying the B-Raf V600E-mutation are associated
      with a poor prognosis. The purpose of this study was to identify B-RafV600E
      mediated traits of cancer cells in a genetic in vitro model and to assess the
      selective sensitization of B-RafV600E-mutant cancer cells towards therapeutic
      agents. METHODS: Somatic cell gene targeting was used to generate subclones of
      the colorectal cancer cell line RKO containing either wild-type or V600E-mutant B
      Raf kinase. Cell-biologic analyses were performed in order to link cancer cell
      traits to the BRAF-mutant genotype. Subsequently, the corresponding tumor cell
      clones were characterized pharmacogenetically to identify therapeutic agents
      exhibiting selective sensitivity in B-RafV600E-mutant cells. RESULTS: Genetic
      targeting of mutant BRAF resulted in restoration of sensitivity to serum
      starvation-induced apoptosis and efficiently inhibited cell proliferation in the
      absence of growth factors. Among tested agents, the B-Raf inhibitor dabrafenib
      was found to induce a strong V600E-dependent shift in cell viability. In
      contrast, no differential sensitizing effect was observed for conventional
      chemotherapeutic agents (mitomycin C, oxaliplatin, paclitaxel, etoposide, 5
      fluorouracil), nor for the targeted agents cetuximab, sorafenib, vemurafenib,
      RAF265, or for inhibition of PI3 kinase. Treatment with dabrafenib efficiently
      inhibited phosphorylation of the B-Raf downstream targets Mek 1/2 and Erk 1/2.
      CONCLUSION: Mutant BRAF alleles mediate self-sufficiency of growth signals and
      serum starvation-induced resistance to apoptosis. Targeting of the BRAF mutation
      leads to a loss of these hallmarks of cancer. Dabrafenib selectively inhibits
      cell viability in B-RafV600E mutant cancer cells.

PMID- 24885692
TI  - Accuracy of epidemiological inferences based on publicly available information:
      retrospective comparative analysis of line lists of human cases infected with
      influenza A(H7N9) in China.
AB  - BACKGROUND: Appropriate public health responses to infectious disease threats
      should be based on best-available evidence, which requires timely reliable data
      for appropriate analysis. During the early stages of epidemics, analysis of 'line
      lists' with detailed information on laboratory-confirmed cases can provide
      important insights into the epidemiology of a specific disease. The objective of
      the present study was to investigate the extent to which reliable epidemiologic
      inferences could be made from publicly-available epidemiologic data of human
      infection with influenza A(H7N9) virus. METHODS: We collated and compared six
      different line lists of laboratory-confirmed human cases of influenza A(H7N9)
      virus infection in the 2013 outbreak in China, including the official line list
      constructed by the Chinese Center for Disease Control and Prevention plus five
      other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of
      Hong Kong and FluTrackers, based on publicly-available information. We
      characterized clinical severity and transmissibility of the outbreak, using line
      lists available at specific dates to estimate epidemiologic parameters, to
      replicate real-time inferences on the hospitalization fatality risk, and the
      impact of live poultry market closure. RESULTS: Demographic information was
      mostly complete (less than 10% missing for all variables) in different line
      lists, but there were more missing data on dates of hospitalization, discharge
      and health status (more than 10% missing for each variable). The estimated onset
      to hospitalization distributions were similar (median ranged from 4.6 to 5.6
      days) for all line lists. Hospital fatality risk was consistently around 20% in
      the early phase of the epidemic for all line lists and approached the final
      estimate of 35% afterwards for the official line list only. Most of the line
      lists estimated >90% reduction in incidence rates after live poultry market
      closures in Shanghai, Nanjing and Hangzhou. CONCLUSIONS: We demonstrated that
      analysis of publicly-available data on H7N9 permitted reliable assessment of
      transmissibility and geographical dispersion, while assessment of clinical
      severity was less straightforward. Our results highlight the potential value in
      constructing a minimum dataset with standardized format and definition, and
      regular updates of patient status. Such an approach could be particularly useful
      for diseases that spread across multiple countries.

PMID- 24885694
TI  - Conversation about Serostatus decreases risk of acquiring HIV: results from a
      case control study comparing MSM with recent HIV infection and HIV negative
      controls.
AB  - BACKGROUND: Data on knowledge, attitudes, behaviour and practices (KABP) of
      persons with recent HIV infection compared to controls with negative HIV test
      result provide information on current risk patterns and can help to re-focus HIV
      prevention strategies. METHODS: From March 2008 through May 2010, persons newly
      diagnosed with HIV (cases) and HIV-negative controls were recruited by physicians
      in Germany. To distinguish recent (< 5 months) from longstanding (> 5 months)
      infection, dried blood spots from people newly diagnosed with HIV were tested
      with the BED IgG-capture ELISA. Cases and controls completed a KABP
      questionnaire. We compared cases with recent infection and controls among men
      having sex with men (MSM) regarding reported risk behaviour in the previous 6
      months. To detect differences, unadjusted Odds Ratios (OR) were calculated and
      multivariate analysis was performed. RESULTS: Cases and controls did not differ
      in terms of knowledge on transmission risks, HIV testing frequency, partnership
      status, or regarding the frequency of any unprotected sex with partners known to
      be HIV-positive or assumed to be HIV-negative. Cases more often reported a
      shorter duration of partnership (< 6 months) with a primary partner than controls
      (OR = 3.9; p = 0.003) and indicated lower rates of condom use outside of primary
      relationships, with acquaintances (OR = 2.5; p = 0.01), and with persons met
      online (OR = 4.5; p = 0.04). Unprotected sex with persons of unknown HIV
      serostatus was more often indicated by cases than controls (OR = 3.0; p = 0.003).
      Having a conversation about HIV serostatus before having sex was associated with
      a lower risk of infection (OR = 0.2; p = 0.01). In multivariate analysis "being
      always safe" (always using a condom when having sex in different situations
      outside of a relationship) and talking about serostatus before sex (OR = 0.23; p
      = 0.004; OR = 0.14; p = 0.014) were negatively associated with HIV- infection.
      CONCLUSIONS: There were no significant differences regarding knowledge about HIV
      transmission risks among cases and controls. Differences in risk behaviour were
      observed regarding unprotected sex with partners of unknown HIV-serostatus and
      duration of primary partnership at the time of diagnosis, suggesting some HIV
      transmissions occurring in newly formed partnerships. The practice of discussing
      serostatus with prospective sex partners before engaging in sex seems to be
      protective for HIV-transmission.

PMID- 24885693
TI  - Large-scale phosphoproteome analysis in seedling leaves of Brachypodium
      distachyon L.
AB  - BACKGROUND: Protein phosphorylation is one of the most important post
      translational modifications involved in the regulation of plant growth and
      development as well as diverse stress response. As a member of the Poaceae,
      Brachypodium distachyon L. is a new model plant for wheat and barley as well as
      several potential biofuel grasses such as switchgrass. Vegetative growth is vital
      for biomass accumulation of plants, but knowledge regarding the role of protein
      phosphorylation modification during vegetative growth, especially in biofuel
      plants, is far from comprehensive. RESULTS: In this study, we carried out the
      first large-scale phosphoproteome analysis of seedling leaves in Brachypodium
      accession Bd21 using TiO2 microcolumns combined with liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) and MaxQuant software. A total of 1470
      phosphorylation sites in 950 phosphoproteins were identified, and these
      phosphoproteins were implicated in various molecular functions and basic cellular
      processes by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathway analyses. Among the 950 phosphoproteins identified, 127 contained
      3 to 8 phosphorylation sites. Conservation analysis showed that 93.4% of the 950
      phosphoproteins had phosphorylation orthologs in other plant species. Motif-X
      analysis of the phosphorylation sites identified 13 significantly enriched
      phosphorylation motifs, of which 3 were novel phosphorylation motifs. Meanwhile,
      there were 91 phosphoproteins with both multiple phosphorylation sites and
      multiple phosphorylation motifs. In addition, we identified 58 phosphorylated
      transcription factors across 21 families and found out 6 significantly over
      represented transcription factor families (C3H, Trihelix, CAMTA, TALE,
      MYB_related and CPP). Eighty-four protein kinases (PKs), 8 protein phosphatases
      (PPs) and 6 CESAs were recognized as phosphoproteins. CONCLUSIONS: Through a
      large-scale bioinformatics analysis of the phosphorylation data in seedling
      leaves, a complicated PKs- and PPs- centered network related to rapid vegetative
      growth was deciphered in B. distachyon. We revealed a MAPK cascade network that
      might play the crucial roles during the phosphorylation signal transduction in
      leaf growth and development. The phosphoproteins and phosphosites identified from
      our study expanded our knowledge of protein phosphorylation modification in
      plants, especially in monocots.

PMID- 24885695
TI  - Wellbeing among sub-Saharan African patients with advanced HIV and/or cancer: an
      international multicentred comparison study of two outcome measures.
AB  - BACKGROUND: Despite the high mortality rates of HIV and cancer in sub-Saharan
      Africa, there are few outcome tools and no comparative data across conditions.
      This study aimed to measure multidimensional wellbeing among advanced HIV and/or
      cancer patients in three African countries, and determine the relationship
      between two validated outcome measures. METHODS: Cross-sectional self-reported
      data from palliative care populations in Kenya, Uganda and South Africa using
      FACIT-G+Pal and POS measures. RESULTS: Among 461 participants across all
      countries, subscale "social and family wellbeing" had highest (best) score.
      Significant country effect showed lower (worse) scores for Uganda on 3 FACIT G
      subscales: Physical, Social + family, and functional. In multiple regression,
      country and functional status accounted for 21% variance in FACIT-Pal. Worsening
      functional status was associated with poorer POS score. Kenyans had worse POS
      score, followed by Uganda and South Africa. Matrix of correlational coefficients
      revealed moderate correlation between the POS and FACIT-Pal core scale (0.60),
      the FACIT-G and POS (0.64), and FACIT-G + Pal with POS (0.66). CONCLUSIONS: The
      data reveal best status for family and social wellbeing, which may reflect the
      sample being from less individualistic societies. The tools appear to measure
      different constructs of wellbeing in palliative care, and reveal different levels
      of wellbeing between countries. Those with poorest physical function require
      greatest palliative and supportive care, and this does not appear to differ
      according to diagnosis.

PMID- 24885696
TI  - Identification of a common reference gene pair for qPCR in human mesenchymal
      stromal cells from different tissue sources treated with VEGF.
AB  - BACKGROUND: Human mesenchymal stromal cells from the bone marrow (BMSCs) are
      widely used as experimental regenerative treatment of ischemic heart disease, and
      the first clinical trials using adipose-derived stromal cells (ASCs) are
      currently being conducted. Regenerative mechanisms of BMSCs and ASCs are manifold
      and in vitro pretreatment of the cells with growth factors has been applied to
      potentially enhance these properties. When characterizing the transcriptional
      activity of these cellular mechanisms in vitro it is important to consider the
      effect of the growth factor treatment on reference genes (RGs) for the
      normalization of qPCR data. RESULTS: BMSCs and ASCs were stimulated with vascular
      endothelial growth factor A-165 (VEGF) for one week, and compared with un
      stimulated cells from the same donor. The stability of nine RGs through VEGF
      treatment as well as the donor variation was assessed using the GenEx software
      with the subprograms geNorm and Normfinder.The procedure of stepwise elimination
      was validated by poor performance of eliminated RGs in a normalization experiment
      using vWF as target gene. Normfinder found the TATA box binding protein (TBP) to
      be the most stable single RG for both BMSCs and ASCs. The optimal number of RGs
      for ASCs was two, and the lowest variance for vWF normalization was found using
      TBP and YWHAZ. For BMSCs, the optimal number of RGs was four, while the two-RG
      combination producing the most similar results was TBP and YWHAZ. CONCLUSIONS: A
      common reference gene, TBP, was found to be the most stable standalone gene,
      while TBP and YWHAZ were found to be the best two-RG combination for qPCR
      analyses for both BMSCs and ASCs through the VEGF stimulation. The presented
      stepwise elimination procedure was validated, while we found the final
      normalization experiment to be essential.

PMID- 24885697
TI  - Early childhood caries and its relationship with perinatal, socioeconomic and
      nutritional risks: a cross-sectional study.
AB  - BACKGROUND: Socioeconomic, perinatal and other life cycle events can be important
      determinants of the health status of the individual and populations. This study
      aimed to assess the prevalence of early childhood caries (ECC), perinatal factors
      (gestational age, teenage pregnancy and birth weight), family income and
      nutritional risk in children. METHODS: A cross-sectional study in which 320
      children were examined according to the criteria established by the World Health
      Organization. A previously validated questionnaire was used to obtain information
      from parents and guardians about family income, gestational age and birth weight.
      To check the nutritional risk, we used the criteria provided by the CDC (Center
      for Disease Control). For Statistics, Pearson's, chi-square and the multivariate
      Poisson analyses were used to determine the association among variables. RESULTS:
      Approximately 20% of children had ECC, and the Poisson multivariate analyses
      indicated that family income (p = 0.009), birth weight (p < 0.001) and infant
      obesity (p < 0.001) were related to the increase of ECC, and gestational age was
      not significantly associated with ECC (p = 0.149). Pregnancy in adolescence was
      not included in the regression analyses model because it was not statistically
      significant in the chi-square test (p > 0.05). CONCLUSION: The prevalence of ECC
      was related to low family income, premature birth and infant obesity.

PMID- 24885699
TI  - Cardiorespiratory fitness and the incidence of type 2 diabetes: a cohort study of
      Japanese male athletes.
AB  - BACKGROUND: In Japan, although the incidence of overweight (BMI >= 25) is still
      low compared with that in Europe and the United States, the prevalence of type 2
      diabetes has increased over the last 15 years,. In both Japanese and Caucasian
      populations it has been reported that a high level of cardiorespiratory fitness
      protects against the development of type 2 diabetes. However, there are no
      reports focused specifically on athletes that investigate whether high
      cardiorespiratory fitness at a young age can prevent disease later in life. We
      examined the relationship between cardiorespiratory fitness at a young age and
      the development of type 2 diabetes in Japanese athletes using a cohort study.
      METHODS: The cardiorespiratory fitness of male alumni of the physical education
      department of Juntendo University, as measured by stored data of a 1,500-m
      endurance run in college (1971-1991) was compared with their incidence of type 2
      diabetes as determined by follow-up questionnaires (2007-2009). This study used
      Cox's proportional hazards models and adjusted for age, year of graduation, BMI,
      smoking, and sports club participation at college age. RESULTS: We collected data
      on cardiorespiratory fitness at college age and medical history survey data
      during 2007-2009 from 570 male alumni. The median follow-up period was 26 years
      (IQR: 23-29 years), and 22 men had developed type 2 diabetes. An inverse
      relationship was observed between incidence of type 2 diabetes and level of
      cardiorespiratory fitness at time of college after adjustment for age, year of
      graduation, BMI, smoking, and sports participation. The adjusted hazards ratio
      and 95% CI by category (low, medium, and high) were 1.00 (reference), 0.40 (0.14
      1.13) and 0.26 (0.07-1.00) (p = 0.03 for trend). CONCLUSIONS: A high level of
      cardiorespiratory fitness at a young age can help prevent type 2 diabetes later
      in life.

PMID- 24885698
TI  - Inferior vena cava prosthetic replacement in a patient with horseshoe kidney and
      metastatic testicular tumor: technical considerations and review of the
      literature.
AB  - BACKGROUND: Seminomatous and non-seminomatous Germ Cell Tumors (GCT) of the
      testis are a rare cancer, with an estimated incidence of 56.3 per million white
      males and 10 per million black males in the United States.The association between
      non-seminomatous GCT and horseshoe kidney is a rare event and is seen in about
      1.3% of patients requiring retroperitoneal lymph node dissection. To our
      knowledge, no cases have been reported in which replacement of the IVC was also
      necessary. CASE PRESENTATION: We report the case of a 22-year-old man with
      horseshoe kidney and metastatic non-seminomatous germ cell tumor involving the
      wall of the inferior vena cava.Following post-chemotherapy retroperitonal lymph
      node dissection, the inferior vena cava was replaced with an expanded
      polytetrafluoroethylene graft.At 2-years follow-up, the patient was in good
      health and the graft was patent. No clinical or diagnostic signs of renal
      impairment or recurrence of neoplastic disease were noted. CONCLUSION: Radical
      surgery is warranted in patients with non-seminomatous germ cell tumor
      metastasizing to the retroperitoneal lymph nodes. When vena cava replacement is
      required, and the situation is further complicated by horseshoe kidney, as in
      this case, surgical technique will rely on multidisciplinary surgical treatment
      planning by a team composed of urologists, vascular surgeons and oncologists.

PMID- 24885700
TI  - Decreasing trends in patient satisfaction, accessibility and continuity of care
      in Finnish primary health care - a 14-year follow-up questionnaire study.
AB  - BACKGROUND: The aim here was to explore trends in patient satisfaction with
      primary health care and its accessibility and continuity, and to explore whether
      through reforms and improvements some of the essential goals had been achieved
      over a 14-year period of time in Finland. METHODS: Nine questionnaire surveys
      were conducted over a period of 14 years among patients attending within one week
      in the 65 health centres in the Tampere University Hospital catchment area. A
      total of 147,394 responded out of a sample of 333,648 patients. The response rate
      varied yearly from 53% to 37%. RESULTS: Patient satisfaction with care in Finnish
      health centres decreased by nearly 9 percentage units from 1998 to 2011. The fall
      off was most marked in the age-group over 64 years. There was a 20 percentage
      unit's reduction in ease of access as reported by patients. Respondents also
      reported that the continuity of care had deteriorated. CONCLUSIONS: Despite major
      reforms in Finnish health care policy, patients seem to be less satisfied. Our
      findings challenge both Finnish authorities and GPs to improve the accessibility
      and continuity of care in primary health services.

PMID- 24885702
TI  - A novel model of double replications and random loss accounts for rearrangements
      in the Mitogenome of Samariscus latus (Teleostei: Pleuronectiformes).
AB  - BACKGROUND: Although more than one thousand complete mitochondrial DNA (mtDNA)
      sequences have been determined in teleostean fishes, only a few gene
      rearrangements have been observed, and genome-scale rearrangements are even
      rarer. However, flatfishes (Pleuronectiformes) have been identified as having
      diverse types of mitochondrial gene rearrangements. It has been reported that
      tongue soles and the blue flounder mitogenomes exhibit different types of large
      scale gene rearrangements. RESULTS: In the present study, the complete
      mitochondrial genome of another flatfish, Samariscus latus, was sequenced, and
      genome-scale rearrangements were observed. The genomic features of this flounder
      are different from those of any other studied vertebrates, including flatfish
      species too. The mitogenome of S. latus is characterized by the duplication and
      translocation of the control region (CR). The genes located between the two CRs
      are divided into two clusters in which their relative orders are maintained.
      CONCLUSIONS: We propose a "Double Replications and Random Loss" model to explain
      the rearrangement events in S. latus mitogenome. This model consists of the
      following steps. First, the CR was duplicated and translocated. Subsequently,
      double replications of the mitogenome were successively initiated from the two
      CRs, leading to the duplication of the genes between the two CRs. Finally, one of
      each pair of duplicated genes was lost in a random event.

PMID- 24885701
TI  - Lactate dehydrogenase A is a potential prognostic marker in clear cell renal cell
      carcinoma.
AB  - BACKGROUND: Over 90% of cancer-related deaths in clear cell renal cell carcinoma
      (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need
      for new molecular markers that can potentiate the efficacy of the current
      clinical-based models of prognosis assessment. The objective of this study is to
      evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed
      by immunohistochemical staining, as a prognostic marker in clear cell renal cell
      carcinoma in relation to clinicopathological features and clinical outcome.
      METHODS: We assessed the expression of LDHA at the protein level, by
      immunohistochemistry, and correlated its expression with multiple
      clinicopathological features including tumor size, clinical stage, histological
      grade, disease-free and overall survival in 385 patients with primary clear cell
      renal cell carcinoma. We also correlated the LDHA expression with overall
      survival, at mRNA level, in an independent data set of 170 clear cell renal cell
      carcinoma cases from The Cancer Genome Atlas databases. Cox proportional hazards
      models adjusted for the potential clinicopathological factors were used to test
      for associations between the LDHA expression and both disease-free survival and
      overall survival. RESULTS: There is statistically significant positive
      correlation between LDHA level of expression and tumor size, clinical stage and
      histological grade. Moreover, LDHA expression shows significantly inverse
      correlation with both disease-free survival and overall survival in patients with
      clear cell renal cell carcinoma. Our results are validated by examining LDHA
      expression, at the mRNA level, in the independent data set of clear cell renal
      cell carcinoma cases from The Cancer Genome Atlas databases which also shows that
      higher lactate dehydrogenase A expression is associated with significantly
      shorter overall survival. CONCLUSION: Our results indicate that LDHA up
      regulation can be a predictor of poor prognosis in clear cell renal cell
      carcinoma. Thus, it represents a potential prognostic biomarker that can boost
      the accuracy of other prognostic models in patients with clear cell renal cell
      carcinoma.

PMID- 24885703
TI  - Clinical baseline factors predict response to natalizumab: their usefulness in
      patient selection.
AB  - BACKGROUND: Optimal patient selection would improve the risk-benefit ratio of
      natalizumab treatment for relapsing-remitting multiple sclerosis (RR MS).
      Clinical features of subjects responding to natalizumab have not been univocally
      recognized. METHODS: Longitudinal data on RR MS patients treated with natalizumab
      in Liguria, Italy are reported. Predictors of relapse occurrence and disability
      improvement were analyzed with a logistic regression method in subjects treated
      for one year (N = 62). A new score, called "Better EDSS Trend (BET)", was devised
      to describe the impact of the treatment on disability. Changes in annualized
      relapse rate (ARR) and Expanded Disability Status Scale (EDSS) after one and two
      years and proportion of disease-free patients were evaluated. RESULTS: Previous
      EDSS worsening plus ARR >= 2 increased the risk of relapse during the treatment
      [Odds Ratio (OR) 4.12, P = 0.04], but this was not associated with an increase in
      disability at one year. EDSS 3.0-3.5 or high disease activity were associated
      with neurological improvement in the first year of treatment (respectively OR
      5.78, P = 0.05 and OR 4.80, P = 0.05). Positive BET score, i.e. improvement in
      the disability trend, was observed in 40.3% of patients, and correlated with high
      ARR in the year before treatment (OR 1.69, P = 0.03). CONCLUSION: Subjects with
      EDSS 3.0-3.5 and those with very active disease in the year before treatment are
      most likely to improve in neurological function under natalizumab. A relapse in
      the first year of treatment is associated to high pre-treatment disease activity;
      however, since the occurrence of a relapse did not have a negative impact on
      clinical improvement at one year, we suggest that it should not lead to treatment
      discontinuation. We propose BET as an additional endpoint of treatment response
      in MS.

PMID- 24885704
TI  - Molecular data and ecological niche modeling reveal population dynamics of
      widespread shrub Forsythia suspensa (Oleaceae) in China's warm-temperate zone in
      response to climate change during the Pleistocene.
AB  - BACKGROUND: Despite its high number of endemic deciduous broad-leaved species in
      China's warm-temperate zone, far less attention has been paid to phylogeographic
      studies in this region. In this work, the phylogeographic history of Forsythia
      suspensa endemic to China's warm-temperate zone was investigated to explore the
      effect of climate change during the Pleistocene on the distribution of this
      deciduous broad-leaved species in China. RESULTS: The cpDNA data revealed seven
      phylogeographical groups corresponding to geographical regions. By contrast, the
      nrDNA data supported the samples clustered into three groups, which was
      inconsistent with separate geographical regions supported by cpDNA data.
      Ecological niche modeling showed that the climatically suitable area during the
      cold period was larger than that during the warm period. CONCLUSIONS: Both
      molecular data and ecological niche modeling indicated that F. suspensa expanded
      to nearby low-elevation plains in the glacial periods, and retreated to
      mountaintops during interglacial warmer stages. This study thus supported that F.
      suspensa persisted in situ during the glacial of the Pleistocene with enlarged
      distribution area, contrary to the hypothesis of long distance southward
      migration or large-scale range contraction.

PMID- 24885705
TI  - Mineral bone disorder in chronic kidney disease: head-to-head comparison of the
      5/6 nephrectomy and adenine models.
AB  - BACKGROUND: Experimental models are important to the understanding of the
      pathophysiology of, as well as the effects of therapy on, certain diseases. In
      the case of chronic kidney disease-mineral bone disorder, there are currently two
      models that are used in evaluating the disease: 5/6 nephrectomy (Nx) and adenine
      induced renal failure (AIRF). However, the two models have never been compared in
      studies using animals maintained under similar conditions. Therefore, we compared
      these two models, focusing on the biochemical, bone histomorphometry, and
      vascular calcification aspects. METHODS: Wistar rats, initially fed identical
      diets, were divided into two groups: those undergoing 5/6 Nx (5/6Nx group) and
      those that were switched to an adenine-enriched diet (AIRF group). After 9 weeks,
      animals were sacrificed, and we conducted biochemical and bone histomorphometry
      analyses, as well as assessing vascular calcification. RESULTS: At sacrifice, the
      mean body weight was higher in the 5/6Nx group than in the AIRF group, as was the
      mean blood pressure. No differences were seen regarding serum phosphate, ionized
      calcium, intact parathyroid hormone (PTH), or fibroblast growth factor 23
      (FGF23). However, creatinine clearance was lower and fractional excretion of
      phosphate (FeP) was higher in the AIRF group rats, which also had a more severe
      form of high-turnover bone disease. Vascular calcification, as evaluated through
      von Kossa staining, was not observed in any of the animals. CONCLUSIONS: Overt
      vascular calcification was not seen in either model as applied in this study.
      Under similar conditions of diet and housing, the AIRF model produces a more
      severe form of bone disease than does 5/6 Nx. This should be taken into account
      when the choice is made between these models for use in preclinical studies.

PMID- 24885706
TI  - A Scopus-based examination of tobacco use publications in Middle Eastern Arab
      countries during the period 2003-2012.
AB  - BACKGROUND: Tobacco smoking is the main health-care problem in the world.
      Evaluation of scientific output in the field of tobacco use has been poorly
      explored in Middle Eastern Arab (MEA) countries to date, and there are few
      internationally published reports on research activity in tobacco use. The main
      objectives of this study were to analyse the research output originating from 13
      MEA countries on tobacco fields and to examine the authorship pattern and the
      citations retrieved from the Scopus database. METHODS: Data from 1 January 2003
      through 31 December 2012 were searched for documents with specific words
      regarding the tobacco field as 'keywords' in the title in any 1 of the 13 MEA
      countries. Research productivity was evaluated based on a methodology developed
      and used in other bibliometric studies. RESULTS: Five hundred documents were
      retrieved from 320 peer-reviewed journals. The greatest amount of research
      activity was from Egypt (25.4%), followed by the Kingdom of Saudi Arabia (KSA)
      (23.2%), Lebanon (16.3%), and Jordan (14.8%). The total number of citations for
      the 560 documents, at the time of data analysis (27 August 2013), was 5,585, with
      a mean +/- SD of 9.95 +/- 22.64 and a median (interquartile range) of 3(1-10).
      The h-index of the retrieved documents was 34. This study identified 232 (41.4%)
      documents from 53 countries in MEA-foreign country collaborations. By region, MEA
      collaborated most often with countries in the Americas (29.6%), followed by
      countries in the same MEA region (13.4%), especially KSA and Egypt. CONCLUSIONS:
      The present data reveal a promising rise and a good start for research
      productivity in the tobacco field in the Arab world. Research output is low in
      some countries, which can be improved by investing in more international and
      national collaborative research projects in the field of tobacco.

PMID- 24885707
TI  - Prevalence and risk factors for periprosthetic fracture in older recipients of
      total hip replacement: a cohort study.
AB  - BACKGROUND: The growing utilization of total joint replacement will increase the
      frequency of its complications, including periprosthetic fracture. The prevalence
      and risk factors of periprosthetic fracture require further study, particularly
      over the course of long-term follow-up. The objective of this study was to
      estimate the prevalence and risk factors for periprosthetic fractures occurring
      in recipients of total hip replacement. METHODS: We identified Medicare
      beneficiaries who had elective primary total hip replacement (THR) for non
      fracture diagnoses between July 1995 and June 1996. We followed them using
      Medicare Part A claims data through 2008. We used ICD-9 codes to identify
      periprosthetic femoral fractures occurring from 2006-2008. We used the incidence
      density method to calculate the annual incidence of these fractures and Cox
      proportional hazards models to identify risk factors for periprosthetic fracture.
      We also calculated the risk of hospitalization over the subsequent year. RESULTS:
      Of 58,521 Medicare beneficiaries who had elective primary THR between July 1995
      and June 1996, 32,463 (55%) survived until January 2006. Of these, 215 (0.7%)
      developed a periprosthetic femoral fracture between 2006 and 2008. The annual
      incidence of periprosthetic fracture among these individuals was 26 per 10,000
      person-years. In the Cox model, a greater risk of periprosthetic fracture was
      associated with having had a total knee replacement (HR 1.82, 95% CI 1.30, 2.55)
      or a revision total hip replacement (HR1.40, 95% CI 0.95, 2.07) between the
      primary THR and 2006. Compared to those without fractures, THR recipients who
      sustained periprosthetic femoral fracture had three-fold higher risk of
      hospitalization in the subsequent year (89% vs. 27%, p<0.0001). CONCLUSION: A
      decade after primary THR, periprosthetic fractures occur annually in 26 per
      10,000 persons and are especially frequent in those with prior total knee or
      revision total hip replacements.

PMID- 24885708
TI  - Microsatellite analysis supports clonal propagation and reduced divergence of
      Trypanosoma vivax from asymptomatic to fatally infected livestock in South
      America compared to West Africa.
AB  - BACKGROUND: Mechanical transmission of the major livestock pathogen Trypanosoma
      vivax by other biting flies than tsetse allows its spread from Africa to the New
      World. Genetic studies are restricted to a small number of isolates and based on
      molecular markers that evolve too slowly to resolve the relationships between
      American and West African populations and, thus, unable us to uncover the recent
      history of T. vivax in the New World. METHODS: T. vivax genetic diversity,
      population structure and the source of outbreaks was investigated through the
      microsatellite multiloci (7 loci) genotype (MLGs) analysis in South America
      (47isolates from Brazil, Venezuela and French Guiana) and West Africa (12
      isolates from The Gambia, Burkina Faso, Ghana, Benin and Nigeria). Relationships
      among MLGs were explored using phylogenetic, principal component and STRUCTURE
      analyses. RESULTS: Although closely phylogenetically related, for the first time,
      genetic differences were detected between T. vivax isolates from South America
      (11 genotypes/47 isolates) and West Africa (12 genotypes/12 isolates) with no
      MLGs in common. Diversity was far greater across West Africa than in South
      America, where genotypes from Brazil (MLG1-6), Venezuela (MLG7-10) and French
      Guiana (MLG11) shared similar but not identical allele composition. No MLG was
      exclusive to asymptomatic (endemic areas) or sick (outbreaks in non-endemic
      areas) animals, but only MLGs1, 2 and 3 were responsible for severe
      haematological and neurological disorders. CONCLUSIONS: Our results revealed
      closely related genotypes of T. vivax in Brazil and Venezuela, regardless of
      endemicity and clinical conditions of the infected livestock. The MLGs analysis
      from T. vivax across SA and WA support clonal propagation, and is consistent with
      the hypothesis that the SA populations examined here derived from common
      ancestors recently introduced from West Africa. The molecular markers defined
      here are valuable to assess the genetic diversity, to track the source and
      dispersion of outbreaks, and to explore the epidemiological and pathological
      significance of T. vivax genotypes.

PMID- 24885709
TI  - Phytochemical constituents, nutritional values, phenolics, flavonols, flavonoids,
      antioxidant and cytotoxicity studies on Phaleria macrocarpa (Scheff.) Boerl
      fruits.
AB  - BACKGROUND: The edible fruits of Phaleria macrocarpa (Scheff.) Boerl are widely
      used in traditional medicine in Indonesia. It is used to treat a variety of
      medical conditions such as - cancer, diabetes mellitus, allergies, liver and
      heart diseases, kidney failure, blood diseases, high blood pressure, stroke,
      various skin diseases, itching, aches, and flu. Therefore, it is of great
      interest to determine the biochemical and cytotoxic properties of the fruit
      extracts. METHODS: The methanol, hexane, chloroform, ethyl acetate, and water
      extracts of P. macrocarpa fruits were examined for phytochemicals,
      physicochemicals, flavonols, flavonoids and phenol content. Its nutritional value
      (A.O.A.C method), antioxidant properties (DPPH assay) and cytotoxicity (MTT cell
      proliferation assay) were also determined. RESULTS: A preliminary phyotochemical
      screening of the different crude extracts from the fruits of P. macrocarpa showed
      the presence secondary metabolites such as of flavonoids, phenols, saponin
      glycosides and tannins. The ethyl acetate and methanol extracts displayed high
      antioxidant acitivity (IC50 value of 8.15+/-0.02 ug/mL) in the DPPH assay
      comparable to that of the standard gallic acid (IC50 value of 10.8+/-0.02 ug/mL).
      Evaluation of cytotoxic activity showed that the crude methanol extract possessed
      excellent anti-proliferative activity against SKOV-3 (IC50 7.75+/-2.56 MUg/mL)
      after 72 hours of treatment whilst the hexane and ethyl acetate extracts
      displayed good cytotoxic effect against both SKOV-3 and MDA-MB231 cell lines. The
      chloroform extract however, showed selective inhibitory activity in the breast
      cancer cell line MDA-MB231 (IC50 7.80+/-1.57 MUg/mL) after 48 hours of treatment.
      There was no cytotoxic effect observed in the Ca Ski cell line and the two normal
      cell lines (MRC-5 and WRL-68). CONCLUSION: The methanol extract and the ethyl
      acetate fraction of P. macrocarpa fruits exhibited good nutritional values, good
      antioxidant and cytotoxic activities, and merits further investigation to
      identify the specific compound(s) responsible for these activities.

PMID- 24885710
TI  - Differential expression and role of hyperglycemia induced oxidative stress in
      epigenetic regulation of beta1, beta2 and beta3-adrenergic receptors in retinal
      endothelial cells.
AB  - BACKGROUND: Aberrant epigenetic profiles are concomitant with a spectrum of
      developmental defects and diseases. Role of methylation is an increasingly
      accepted factor in the pathophysiology of diabetes and its associated
      complications. This study aims to examine the correlation between oxidative
      stress and methylation of beta1, beta2 and beta3-adrenergic receptors and to
      analyze the differential variability in the expression of these genes under
      hyperglycemic conditions. METHODS: Human retinal endothelial cells were cultured
      in CSC complete medium in normal (5 mM) or high (25 mM) glucose to mimic a
      diabetic condition. Reverse transcription PCR and Western Blotting were performed
      to examine the expression of beta1, beta2 and beta3-adrenergic receptors. For
      detections, immunocytochemistry was used. Bisulfite sequencing method was used
      for promoter methylation analysis. Apoptosis was determined by the terminal
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay.
      Dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to measure reactive
      oxygen species (ROS) production in the cells. RESULTS: beta1 and beta3-adrenergic
      receptors were expressed in retinal endothelial cells while beta2-adrenergic
      receptor was not detectable both at protein and mRNA levels. Hyperglycemia had no
      significant effect on beta1 and beta2-adrenergic receptors methylation and
      expression however beta3-adrenergic receptors showed a significantly higher
      expression (p < 0.05) and methylation (p < 0.01) in high and low glucose
      concentration respectively. Apoptosis and oxidative stress were inversely
      correlated with beta3-adrenergic receptors methylation with no significant effect
      on beta1 and beta2-adrenergic receptors. beta2-adrenergic receptor was
      hypermethylated with halted expression. CONCLUSION: Our study demonstrates that
      beta1 and beta3-adrenergic receptors expressed in human retinal endothelial
      cells. Oxidative stress and apoptosis are inversely proportional to the extent of
      promoter methylation, suggesting that methylation loss might be due to oxidative
      stress-induced DNA damage.

PMID- 24885712
TI  - Providing newborn resuscitation at the mother's bedside: assessing the safety,
      usability and acceptability of a mobile trolley.
AB  - BACKGROUND: Deferring cord clamping at very preterm births may be beneficial for
      babies. However, deferring cord clamping should not mean that newborn
      resuscitation is deferred. Providing initial care at birth at the mother's
      bedside would allow parents to be present during resuscitation, and would
      potentially allow initial care to be given with the cord intact. The aim of this
      study was to evaluate the usability of a new mobile trolley for providing newborn
      resuscitation by describing the range of resuscitation procedures performed on a
      group of babies, to assess the acceptability to clinicians compared with standard
      equipment, based on a questionnaire survey, to assess safety from post
      resuscitation temperature measurements and serious adverse event reports and to
      assess whether the trolley allowed resuscitation with the umbilical cord intact
      by assessing the proportion of babies that could be placed on the trolley to
      allow resuscitation with the cord intact. METHODS: The trolley was used when the
      attendance of a clinician trained in newborn life support was required at a
      birth. Clinicians were asked to complete a questionnaire about their experience
      of using the trolley. Serious adverse events were reported. RESULTS: 78 babies
      were managed on the trolley. Median (range) gestation was 34 weeks (24 to 41
      weeks). Median (range) birth weight was 2470 grams (520 to 4080 grams). The full
      range of resuscitation procedures has been successfully provided, although only
      one baby required emergency umbilical venous catheterisation. 77/78 babies had a
      post resuscitation temperature above 36 degrees C. There were no adverse events.
      Most clinicians rated the trolley as 'the same', 'better' or 'much better' than
      conventional resuscitation equipment. In most situations, the baby could be
      resuscitated with umbilical cord intact, although on 18 occasions the cord was
      too short to reach the trolley. CONCLUSIONS: Immediate stabilisation at birth and
      resuscitation can be performed successfully and safely at the bedside using this
      trolley. In most cases this could be achieved with an intact umbilical cord.

PMID- 24885711
TI  - Valproic acid sensitizes pancreatic cancer cells to natural killer cell-mediated
      lysis by upregulating MICA and MICB via the PI3K/Akt signaling pathway.
AB  - BACKGROUND: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is
      reported to exert anti-tumor effects by upregulating the expression of the
      natural killer group 2D (NKG2D) ligands on tumor cells; however, the mechanisms
      vary in different tumor types, and the effect and mechanism of action of VPA in
      pancreatic cancer cells are unknown. METHODS: The present study evaluated the
      effect of VPA to susceptibility of pancreatic cancer cells to the NK cell
      mediated lysis in vitro and in vivo. Then we investigated the mechanism which the
      effect of VPA depend on. RESULTS: The lactate dehydrogenase assay (LDH) and
      xenograft experiment demonstrated that VPA significantly sensitized pancreatic
      cancer cells to NK cell-mediated lysis in vitro and in vivo. Quantitative real
      time- polymerase chain reaction (qRT-PCR) and flow cytometry demonstrated that
      VPA upregulated the mRNA and cell surface expression of the NKG2D ligands major
      histocompatibility complex class I-related chain A and B (MICA and MICB) in
      pancreatic cancer cells. Effects of VPA both in vitro and in vivo were
      significantly attenuated by the PI3K/Akt pathway inhibitor LY294002 or a siRNA
      targeting PI3K catalytic subunit alpha isoform (PI3KCA). CONCLUSION: VPA enhances
      the susceptibility of pancreatic cancer cells to NK cell-mediated cytotoxicity
      both in vitro and in vivo by upregulating the expression of MICA and MICB via a
      PI3K/Akt signaling pathway-dependent mechanism.

PMID- 24885713
TI  - Objective assessment of changes in nuclear morphology and cell distribution
      following induction of apoptosis.
AB  - BACKGROUND: To objectively measure changes in nuclear morphology and cell
      distribution following induction of apoptosis. METHODS: A spontaneously
      immortalized retinal pigment epithelial cell line (ARPE-19) was cultured for
      three days in DMEM/F12 with 10% fetal bovine serum followed by 24 hours
      incubation in staurosporine to induce apoptosis. Cells that were not incubated in
      staurosporine served as control. Caspase-3 expression in apoptotic cells was
      demonstrated by quantitative immunofluorescence. Nuclei were counterstained with
      DAPI. Assessments of nuclear morphology and cell distribution were performed
      using ImageJ software. Statistical analyses included Student's t-test and
      Pearson's correlation coefficient. Nearest neighbor analysis was used to assess
      cell nuclei distribution. RESULTS: Caspase-3 expression in staurosporine
      incubated cells increased by 471% +/- 182% compared to control (P=0.014).
      Relative to the control, cells in the staurosporine-incubated cultures had
      smaller average nuclear area (68% +/- 5%; P<0.001) and nuclear circumference (78
      +/- 3%; P<0.001), while nuclear form factor was larger (110% +/- 1%; P<0.001).
      Cell nuclei from the staurosporine-group (R=1.12 +/- 0.04; P<0.01) and the
      control (R=1.28 +/- 0.03; P<0.01) were evenly spaced throughout the cultures,
      thereby demonstrating a non-clustered and non-random cell distribution. However,
      the staurosporine-incubated group had a significantly lower R-value compared to
      the control (P=0.002), which indicated a move towards cell clustering following
      induction of apoptosis. Caspase-3 expression of each individual cell correlated
      significantly with the following morphological indicators: circumference of the
      nucleus divided by form factor (r=-0.475; P<0.001), nuclear area divided by form
      factor (r=-0.470; P<0.001), nuclear circumference (r=-0.469; P<0.001), nuclear
      area (r=-0.445; P<0.001), nuclear form factor (r=0.410; P<0.001) and the nuclear
      area multiplied by form factor) (r=-0.377; P<0.001). CONCLUSIONS: Caspase-3
      positive apoptotic cells demonstrate morphological features that can be
      objectively quantified using freely available ImageJ software. A novel
      morphological indicator, defined as the nuclear circumference divided by form
      factor, demonstrated the strongest correlation with caspase-3 expression. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3271993311662947.

PMID- 24885715
TI  - Indigenous knowledge, use and on-farm management of enset (Ensete ventricosum
      (Welw.) Cheesman) diversity in Wolaita, Southern Ethiopia.
AB  - BACKGROUND: Ensete ventricosum (Welw.) Cheesman is a major food security crop in
      Southern Ethiopia, where it was originally domesticated and during millennia
      became pivotal crop around which an entire farming system has developed. Although
      its cultivation is highly localized, the enset-based farming system provides
      sustenance to more than 20 million people. Precise ethnobotanical information of
      intra-specific enset diversity and local knowledge on how communities maintain,
      manage and benefit from enset genetic resources is imperative for the promotion,
      conservation and improvement of this crop and its farming system. METHODS: This
      study was conducted in Southern Ethiopia among the Wolaita 'enset culture'
      community. The research sample consisted of 270 households from 12 Kebeles
      (villages) representing three agro-ecological ranges. By establishing
      Participatory Rural Appraisal (PRA) based interactions and applying
      ethnobotanical interviewing methods of free-listing and open-ended
      questionnaires, information on the use and management of enset diversity, and its
      associated folk-biosystematics, food traditions and material culture was
      collected and analyzed. RESULTS: While enset agriculture is seen as cultural
      heritage and identity for the Wolaita, enset intra-specific diversity holds
      scenic, prestige and symbolic values for the household. In the present study we
      recorded 67 enset landraces under cultivation, and through a comprehensive
      literature review we identified 28 landraces reported from other areas of
      Wolaita, but not encountered in our survey. Landraces, identified using 11
      descriptors primarily related to agro-morphological traits, are named after
      perceived places of origin, agro-morphological characteristics and cooking
      quality attributes. Folk classification of enset is based on its domestication
      status, 'gender', agro-ecological adaptability and landrace suitability for
      different food and other uses (fiber, feed, medicinal). Enset as a food crop is
      used to prepare 10 different dishes in Wolaita, 8 of which are exclusively
      prepared using enset, and their consumption ranges from daily staple to specialty
      food in festive occasions and ceremonies. On-farm landrace diversity and richness
      is guided by household needs; its dynamics is managed through regular
      propagation, harvesting restrain, control of landrace composition and arrangement
      in the enset homegardens. CONCLUSIONS: This study reported on the knowledge
      system, socio-cultural process and community practices that drive the maintenance
      of intra-specific on-farm enset diversity in Wolaita, Southern Ethiopia. The
      information is crucial for developing community based complementary in situ and
      ex situ conservation strategies to foster conservation of enset genetic resources
      and associated indigenous knowledge system.

PMID- 24885714
TI  - Outcome of artemether-lumefantrine treatment for uncomplicated malaria in HIV
      infected adult patients on anti-retroviral therapy.
AB  - BACKGROUND: Malaria and HIV infections are both highly prevalent in sub-Saharan
      Africa, with HIV-infected patients being at higher risks of acquiring malaria.
      The majority of antiretroviral (ART) and anti-malarial drugs are metabolized by
      the CYP450 system, creating a chance of drug-drug interaction upon co
      administration. Limited data are available on the effectiveness of the artemether
      lumefantrine combination (AL) when co-administered with non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). The aim of this study was to compare anti
      malarial treatment responses between HIV-1 infected patients on either nevirapine
      or efavirenz-based treatment and those not yet on ART (control-arm) with
      uncomplicated falciparum malaria, treated with AL. METHOD: This was a
      prospective, non-randomized, open-label study conducted in Bagamoyo district,
      with three arms of HIV-infected adults: efavirenz-based treatment arm (EFV-arm) n
      = 66, nevirapine-based treatment arm (NVP-arm) n = 128, and control-arm n = 75,
      with uncomplicated malaria. All patients were treated with AL and followed up for
      28 days. The primary outcome measure was an adequate clinical and parasitological
      response (ACPR) after treatment with AL by day 28. RESULTS: Day 28 ACPR was
      97.6%, 82.5% and 94.5% for the NVP-arm, EFV-arm and control-arm, respectively. No
      early treatment or late parasitological failure was reported. The cumulative risk
      of recurrent parasitaemia was >19-fold higher in the EFV-arm than in the control
      arm (Hazard ratio [HR], 19.11 [95% confidence interval {CI}, 10.5-34.5]; P <
      0.01). The cumulative risk of recurrent parasitaemia in the NVP-arm was not
      significantly higher than in the control-arm ([HR], 2.44 [95% {CI}, 0.79-7.6]; P
      = 0.53). The median (IQR) day 7 plasma concentrations of lumefantrine for the
      three arms were: 1,125 ng/m (638.8-1913), 300.4 ng/ml (220.8-343.1) and 970 ng/ml
      (562.1-1729) for the NVP-arm, the EFV-arm and the control-arm, respectively (P <
      0.001). In all three arms, the reported adverse events were mostly mild.
      CONCLUSION: After 28 days of follow-up, AL was statistically safe and effective
      in the treatment of uncomplicated malaria in the NVP-arm. The results of this
      study also provide an indication of the possible impact of EFV on the performance
      of AL and the likelihood of it affecting uncomplicated falciparum malaria
      treatment outcome.

PMID- 24885716
TI  - Disinvestment policy and the public funding of assisted reproductive
      technologies: outcomes of deliberative engagements with three key stakeholder
      groups.
AB  - BACKGROUND: Measures to improve the quality and sustainability of healthcare
      practice and provision have become a policy concern. In addition, the involvement
      of stakeholders in health policy decision-making has been advocated, as complex
      questions arise around the structure of funding arrangements in a context of
      limited resources. Using a case study of assisted reproductive technologies
      (ART), deliberative engagements with a range of stakeholder groups were held on
      the topic of how best to structure the distribution of Australian public funding
      in this domain. METHODS: Deliberative engagements were carried out with groups of
      ART consumers, clinicians and community members. The forums were informed by a
      systematic review of ART treatment safety and effectiveness (focusing, in
      particular, on maternal age and number of treatment cycles), as well as by
      international policy comparisons, and ethical and cost analyses. Forum
      discussions were transcribed and subject to thematic analysis. RESULTS: Each
      forum demonstrated stakeholders' capacity to understand concepts of choice under
      resource scarcity and disinvestment, and to countenance options for ART funding
      not always aligned with their interests. Deliberations in each engagement
      identified concerns around 'equity' and 'patient responsibility', culminating in
      a broad preference for (potential) ART subsidy restrictions to be based upon
      individual factors rather than maternal age or number of treatment cycles.
      Community participants were open to restrictions based upon measures of body mass
      index (BMI) and smoking status, while consumers and clinicians saw support to
      improve these factors as part of an ART treatment program, as distinct from a
      funding criterion. All groups advocated continued patient co-payments, with
      measures in place to provide treatment access to those unable to pay (namely,
      equity of access). CONCLUSIONS: Deliberations yielded qualitative, socially
      negotiated evidence required to inform ethical, accountable policy decisions in
      the specific area of ART and health care more broadly. Notably, reductionist,
      deterministic characterizations of stakeholder 'self-interest' proved unfounded
      as each group sought to prioritise universal values (in particular, 'equity' and
      'responsibility') over specific, within-group concerns. Our results--from an
      emotive case study in ART--highlight that evidence-informed disinvestment
      decision-making is feasible, and potentially less controversial than often
      presumed.

PMID- 24885718
TI  - Alcohol marketing in televised international football: frequency analysis.
AB  - BACKGROUND: Alcohol marketing includes sponsorship of individuals, organisations
      and sporting events. Football (soccer) is one of the most popular spectator
      sports worldwide. No previous studies have quantified the frequency of alcohol
      marketing in a high profile international football tournament. The aims were to
      determine: the frequency and nature of visual references to alcohol in a
      representative sample of EURO2012 matches broadcast in the UK; and if frequency
      or nature varied between matches broadcast on public service and commercial
      channels, or between matches that did and did not feature England. METHODS: Eight
      matches selected by stratified random sampling were recorded. All visual
      references to alcohol were identified using a tool with high inter-rater
      reliability. RESULTS: 1846 visual references to alcohol were identified over 1487
      minutes of broadcast--an average of 1.24 references per minute. The mean number
      of references per minute was higher in matches that did vs did not feature
      England (p = 0.004), but did not differ between matches broadcast on public
      service vs commercial channels (p = 0.92). CONCLUSIONS: The frequency of visual
      references to alcohol was universally high and higher in matches featuring the
      only UK home team--England--suggesting that there may be targeting of
      particularly highly viewed matches. References were embedded in broadcasts, and
      not particular to commercial channels including paid-for advertising. New UK
      codes-of-conduct on alcohol marketing at sporting events will not reduce the
      level of marketing reported here.

PMID- 24885717
TI  - Multiple transcription factors directly regulate Hox gene lin-39 expression in
      ventral hypodermal cells of the C. elegans embryo and larva, including the
      hypodermal fate regulators LIN-26 and ELT-6.
AB  - BACKGROUND: Hox genes encode master regulators of regional fate specification
      during early metazoan development. Much is known about the initiation and
      regulation of Hox gene expression in Drosophila and vertebrates, but less is
      known in the non-arthropod invertebrate model system, C. elegans. The C. elegans
      Hox gene lin-39 is required for correct fate specification in the midbody region,
      including the Vulval Precursor Cells (VPCs). To better understand lin-39
      regulation and function, we aimed to identify transcription factors necessary for
      lin-39 expression in the VPCs, and in particular sought factors that initiate lin
      39 expression in the embryo. RESULTS: We used the yeast one-hybrid (Y1H) method
      to screen for factors that bound to 13 fragments from the lin-39 region: twelve
      fragments contained sequences conserved between C. elegans and two other nematode
      species, while one fragment was known to drive reporter gene expression in the
      early embryo in cells that generate the VPCs. Sixteen transcription factors that
      bind to eight lin-39 genomic fragments were identified in yeast, and we
      characterized several factors by verifying their physical interactions in vitro,
      and showing that reduction of their function leads to alterations in lin-39
      levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan
      nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the
      GATA factor ELT-6 positively regulate lin-39 expression in the embryonic
      precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that
      drives GFP expression in the early embryo, and the ELT-6 site we identified is
      necessary for proper embryonic expression. These three factors, along with the
      factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in
      the larval VPCs. CONCLUSIONS: These results significantly expand the number of
      factors known to directly bind and regulate lin-39 expression, identify the first
      factors required for lin-39 expression in the embryo, and hint at a positive
      feedback mechanism involving GATA factors that maintains lin-39 expression in the
      vulval lineage. This work indicates that, as in other organisms, the regulation
      of Hox gene expression in C. elegans is complicated, redundant and robust.

PMID- 24885719
TI  - The effects of a low international normalized ratio on thromboembolic and
      bleeding complications in patients with mechanical mitral valve replacement.
AB  - BACKGROUND: Mechanical heart valve replacement has an inherent risk of
      thromboembolic events (TEs). Current guidelines recommend an international
      normalized ratio (INR) of at least 2.5 after mechanical mitral valve replacement
      (MVR). This study aimed to evaluate the effects of a low INR (2.0-2.5) on
      thromboembolic and bleeding complications in patients with mechanical MVR on
      warfarin therapy. METHODS: One hundred and thirty-five patients who underwent
      mechanical MVR were enrolled in this study. The end points of this study were
      defined as TEs (valve thrombosis, transient ischemic attack, stroke) and bleeding
      (all minor and major bleeding) complications. Patients were followed up for a
      mean of 39.6 months and the mean INR of the patients was calculated. After data
      collection, patients were divided into 3 groups according to their mean INR, as
      follows: group 1 (n = 34), INR <2.0; group 2 (n = 49), INR 2.0-2.5; and group 3
      (n = 52), INR >2.5. RESULTS: A total of 22 events (10 [7.4%] thromboembolic and
      12 [8.8%] bleeding events) occurred in the follow-up period. The mean INR was an
      independent risk factor for the development of TEs. Mean INR and neurological
      dysfunction were independent risk factors for the development of bleeding events.
      A statistically significant positive correlation was found between the log mean
      INR and all bleeding events, and a negative correlation was found between the log
      mean INR and all TEs. The total number of events was significantly lower in group
      2 than in groups 1 and 3 (P = 0.036). CONCLUSIONS: This study showed that a
      target INRs of 2.0-2.5 are acceptable for preventing TEs and safe in terms of
      bleeding complications in patients with mechanical MVR.

PMID- 24885720
TI  - Ethics of neuroimaging after serious brain injury.
AB  - BACKGROUND: Patient outcome after serious brain injury is highly variable.
      Following a period of coma, some patients recover while others progress into a
      vegetative state (unresponsive wakefulness syndrome) or minimally conscious
      state. In both cases, assessment is difficult and misdiagnosis may be as high as
      43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic
      resonance imaging and electroencephalography have been used to detect residual
      cognitive function in vegetative and minimally conscious patients. Neuroimaging
      may improve diagnosis and prognostication. These techniques are beginning to be
      applied to comatose patients soon after injury. Evidence of preserved cognitive
      function may predict recovery, and this information would help families and
      health providers. Complex ethical issues arise due to the vulnerability of
      patients and families, difficulties interpreting negative results, restriction of
      communication to "yes" or "no" answers, and cost. We seek to investigate ethical
      issues in the use of neuroimaging in behaviorally nonresponsive patients who have
      suffered serious brain injury. The objectives of this research are to: (1) create
      an approach to capacity assessment using neuroimaging; (2) develop an ethics of
      welfare framework to guide considerations of quality of life; (3) explore the
      impact of neuroimaging on families; and, (4) analyze the ethics of the use of
      neuroimaging in comatose patients. METHODS/DESIGN: Our research program
      encompasses four projects and uses a mixed methods approach. Project 1 asks
      whether decision making capacity can be assessed in behaviorally nonresponsive
      patients. We will specify cognitive functions required for capacity and detail
      their assessment. Further, we will develop and pilot a series of scenarios and
      questions suitable for assessing capacity. Project 2 examines the ethics of
      welfare as a guide for neuroimaging. It grounds an obligation to explore
      patients' interests, and we explore conceptual issues in the development of a
      quality of life instrument adapted for neuroimaging. Project 3 will use grounded
      theory interviews to document families' understanding of the patient's condition,
      expectations of neuroimaging, and the impact of the results of neuroimaging.
      Project 4 will provide an ethical analysis of neuroimaging to investigate
      residual cognitive function in comatose patients within days of serious brain
      injury.

PMID- 24885721
TI  - A review of machine learning methods to predict the solubility of overexpressed
      recombinant proteins in Escherichia coli.
AB  - BACKGROUND: Over the last 20 years in biotechnology, the production of
      recombinant proteins has been a crucial bioprocess in both biopharmaceutical and
      research arena in terms of human health, scientific impact and economic volume.
      Although logical strategies of genetic engineering have been established, protein
      overexpression is still an art. In particular, heterologous expression is often
      hindered by low level of production and frequent fail due to opaque reasons. The
      problem is accentuated because there is no generic solution available to enhance
      heterologous overexpression. For a given protein, the extent of its solubility
      can indicate the quality of its function. Over 30% of synthesized proteins are
      not soluble. In certain experimental circumstances, including temperature,
      expression host, etc., protein solubility is a feature eventually defined by its
      sequence. Until now, numerous methods based on machine learning are proposed to
      predict the solubility of protein merely from its amino acid sequence. In spite
      of the 20 years of research on the matter, no comprehensive review is available
      on the published methods. RESULTS: This paper presents an extensive review of the
      existing models to predict protein solubility in Escherichia coli recombinant
      protein overexpression system. The models are investigated and compared regarding
      the datasets used, features, feature selection methods, machine learning
      techniques and accuracy of prediction. A discussion on the models is provided at
      the end. CONCLUSIONS: This study aims to investigate extensively the machine
      learning based methods to predict recombinant protein solubility, so as to offer
      a general as well as a detailed understanding for researches in the field. Some
      of the models present acceptable prediction performances and convenient user
      interfaces. These models can be considered as valuable tools to predict
      recombinant protein overexpression results before performing real laboratory
      experiments, thus saving labour, time and cost.

PMID- 24885722
TI  - Using Global Positioning Systems (GPS) and temperature data to generate time
      activity classifications for estimating personal exposure in air monitoring
      studies: an automated method.
AB  - BACKGROUND: Personal exposure studies of air pollution generally use self
      reported diaries to capture individuals' time-activity data. Enhancements in the
      accuracy, size, memory and battery life of personal Global Positioning Systems
      (GPS) units have allowed for higher resolution tracking of study participants'
      locations. Improved time-activity classifications combined with personal
      continuous air pollution sampling can improve assessments of location-related air
      pollution exposures for health studies. METHODS: Data was collected using a GPS
      and personal temperature from 54 children with asthma living in Montreal, Canada,
      who participated in a 10-day personal air pollution exposure study. A method was
      developed that incorporated personal temperature data and then matched a
      participant's position against available spatial data (i.e., road networks) to
      generate time-activity categories. The diary-based and GPS-generated time
      activity categories were compared and combined with continuous personal PM2.5
      data to assess the impact of exposure misclassification when using diary-based
      methods. RESULTS: There was good agreement between the automated method and the
      diary method; however, the automated method (means: outdoors = 5.1%, indoors
      other =9.8%) estimated less time spent in some locations compared to the diary
      method (outdoors = 6.7%, indoors other = 14.4%). Agreement statistics (AC1 =
      0.778) suggest 'good' agreement between methods over all location categories.
      However, location categories (Outdoors and Transit) where less time is spent show
      greater disagreement: e.g., mean time "Indoors Other" using the time-activity
      diary was 14.4% compared to 9.8% using the automated method. While mean daily
      time "In Transit" was relatively consistent between the methods, the mean daily
      exposure to PM2.5 while "In Transit" was 15.9 MUg/m3 using the automated method
      compared to 6.8 MUg/m3 using the daily diary. CONCLUSIONS: Mean times spent in
      different locations as categorized by a GPS-based method were comparable to those
      from a time-activity diary, but there were differences in estimates of exposure
      to PM2.5 from the two methods. An automated GPS-based time-activity method will
      reduce participant burden, potentially providing more accurate and unbiased
      assessments of location. Combined with continuous air measurements, the higher
      resolution GPS data could present a different and more accurate picture of
      personal exposures to air pollution.

PMID- 24885723
TI  - Combination of gene expression patterns in whole blood discriminate between
      tuberculosis infection states.
AB  - BACKGROUND: Genetic factors are involved in susceptibility or protection to
      tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels
      of gene expression, induced by non-genetic factors, may also determine whether
      individuals progress to active TB. METHODS: We analysed the expression level of
      45 genes in a total of 47 individuals (23 healthy household contacts and 24 new
      smear-positive pulmonary TB patients) in Addis Ababa using a dual colour
      multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess
      gene expression profiles that may be used to distinguish TB cases and their
      contacts and also latently infected (LTBI) and uninfected household contacts.
      RESULTS: The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO,
      MMP9, CCL19, and LTF had significant discriminatory power between sputum smear
      positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79,
      0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1,
      FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of
      household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3
      showed significant difference between LTBI and uninfected contacts, with AUCs of
      0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3,
      FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts.
      CONCLUSIONS: Expression of single and especially combinations of host genes can
      accurately differentiate between active TB cases and healthy individuals as well
      as between LTBI and uninfected contacts.

PMID- 24885724
TI  - Analysis of inter-patient variations in tumour growth rate.
AB  - PURPOSE: Inter-patient variations in tumour growth rate are usually interpreted
      as biological heterogeneity among patients due to, e.g., genetic variability.
      However, these variations might be a result of non-exponential, e.g. the
      Gompertzian, tumour growth kinetics. The aim was to study if the natural tumour
      growth deceleration, i.e. non-exponential growth, is a dominant factor in such
      variations. MATERIALS AND METHODS: The correlation between specific growth rate
      (SGR) and the logarithm of tumour volume, Ln(V), was calculated for tumours in
      patients with meningioma, hepatocellular carcinoma, pancreatic carcinoma, primary
      lung cancer, post-chemotherapy regrowth of non-small cell lung cancer (NSCLC),
      and in nude mice transplanted with human midgut carcinoid GOT1, a tumour group
      which is biologically more homogeneous than patient groups. RESULTS: The
      correlation between SGR and Ln(V) was statistically significant for meningioma,
      post-chemotherapy regrowth of NSCLC, and the mouse model, but not for any other
      patient groups or subgroups, based on differentiation and clinical stage.
      CONCLUSION: This method can be used to evaluate the homogeneity of tumour growth
      kinetics among patients. Homogeneity of post-chemotherapy regrowth pattern of
      NSCLC suggests that, in contrast to untreated tumours, the remaining resistant
      cells or stem cells (if exist) might have similar biological characteristics
      among these patients.

PMID- 24885726
TI  - Successful surgical treatment of extrahepatic biliary papillomatosis diagnosed
      with endoscopic retrograde cholangiopancreatography: a case report.
AB  - INTRODUCTION: Biliary papillomatosis is a condition characterized by multiple
      papillary tumors of variable distribution and extent within the biliary tract.
      Papillary carcinoma can develop in these lesions. It is a rare biliary
      pathological entity and its clinical features and outcome are not well known.
      CASE PRESENTATION: We experienced a case of biliary papillomatosis in a 51-year
      old North African man who presented with obstructive jaundice. Laboratory tests
      showed elevated bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase
      levels. Imaging (ultrasound and magnetic resonance imaging) was suggestive of
      Klatskin tumor associated to common bile duct stones. After endoscopic retrograde
      cholangiopancreatography, a balloon sweep retrieved friable tissue from his bile
      ducts. Histology demonstrated papillary adenomatous proliferation showing high
      grade dysplasia and he was referred for surgical management. CONCLUSIONS:
      Although biliary papillomatosis is rare, it is a premalignant condition that
      should be well known and considered in all diagnoses of obstructive jaundice. We
      report a new case of biliary papillomatosis and highlight the contribution of
      endoscopic retrograde cholangiopancreatography in the diagnosis of this
      condition.

PMID- 24885725
TI  - Spontaneous rupture of a giant gastrointestinal stromal tumor of the jejunum: a
      case report and literature review.
AB  - A few cases of a gastrointestinal stromal tumor (GIST) of the small intestine
      presenting as rupture have been reported in the medical literature. We report an
      unusual case of a large GIST of the jejunum that presented as a spontaneous
      rupture. A 70-year-old man was referred to our hospital because of fever and
      abdominal pain. An abdominal enhanced computed tomography (CT) scan detected a 10
      cm tumor with heterogeneous staining, suggesting necrosis or abscess inside the
      tumor. The patient was treated with antibiotics but inflammation persisted and an
      operation was performed. Intraoperative findings showed an outgrowing 10-cm mass
      in the jejunum near Treitz's ligament. The tumor had ruptured with peritoneal
      metastasis. The solid parenchyma contained a focal area of necrosis within and
      the small ulcer located in the wall of the jejunum presented a communication with
      the large tumor cavity. H&E staining showed spindle-shaped cell proliferation,
      and immunohistochemical staining showed results positive for c-kit and CD34. The
      patient received a diagnosis of a GIST (high-risk group) of the jejunum and was
      treated with imatinib mesylate. The patient has remained in good health without
      recurrence or metastasis one year after the surgical procedure. 

PMID- 24885727
TI  - Provision of group psychoeducation for relatives of persons in inpatient
      depression treatment--a cross-sectional survey of acute care hospitals in
      Germany.
AB  - BACKGROUND: Depressive disorders are often recurrent and place a high burden on
      patients and their relatives. Psychoeducational groups for relatives may reduce
      relatives' burden, help prevent relapses in patients, and are recommended by the
      German "National Disease Management Guideline Unipolar Depression". Since there
      is limited knowledge on the provision of psychoeducational groups for relatives
      of persons in inpatient depression treatment, we conducted a survey among acute
      care hospitals in Germany. METHODS: We conducted a two-step cross-sectional
      survey. Step I consisted of a questionnaire asking the heads of all
      psychiatric/psychosomatic acute care hospitals in Germany (N = 512) whether
      psychoeducational groups for relatives were provided within depression treatment,
      and if not, the reasons for not implementing them. In group offering hospitals
      the person responsible for conducting psychoeducational groups received a
      detailed questionnaire on intervention characteristics (step II). We performed
      descriptive data analysis. RESULTS: The response rate was 50.2% (N = 257) in step
      I and 58.4% in step II (N = 45). 35.4% of the responding hospitals offered
      psychoeducational groups for relatives of patients with depressive disorders.
      According to the estimates of the respondents, relatives of about one in five
      patients took part in psychoeducational groups in 2011. Groups were mostly
      provided by two moderators (62.2%) as continuous groups (77.8%), without
      patients' participation (77.8%), with up to ten participants (65.9%), consisting
      of four or fewer sessions (51.5%) which lasted between one and one and a half
      hours each (77.8%). The moderators in charge were mostly psychologists (43.9%) or
      physicians (26.8%). Approximately one third used published manuals. Reasons for
      not conducting such psychoeducational groups were lack of manpower (60.1%), time
      (44.9%) and financial constraints (24.1%). 25.3% mentioned adequate concepts of
      intervention as a required condition for initiating such groups. CONCLUSIONS:
      Only a small proportion of relatives of patients with depressive disorders
      participated in psychoeducational groups in 2011 in Germany. Mostly short
      interventions were favoured and main implementation barriers were scarce
      resources. Brief interventions that fit with healthcare routine should be
      developed and tested within randomised controlled trials. This could promote the
      provision of psychoeducational groups for relatives as evidence-based practice in
      inpatient depression treatment in Germany.

PMID- 24885728
TI  - Influence of substrate on electricity generation of Shewanella loihica PV-4 in
      microbial fuel cells.
AB  - BACKGROUND: The substrate, serving as carbon and energy source, is one of the
      major factors affecting the performance of microbial fuel cells (MFCs). We
      utilized BIOLOG system to rapidly screen substrates for electricigens, and
      further evaluated influence of these substrates on electricity generation of
      Shewanella loihica PV-4 in MFCs. RESULTS: Three of most favorable substrates
      (lactate acid, formic acid and cyclodextrin) with OD590/750 of 0.952, 0.880 and
      0.849 as well as three of most unfavorable substrates (galactose, arabinose and
      glucose) with OD590/750 of 0.248, 0.137 and 0.119 were selected by BIOLOG system
      under aerobic conditions. The chronoamperometry results showed that MFCs fed with
      these substrates exhibited different current behaviors. Cyclic voltammograms
      results showed that arabinose, galactose and glucose promoted electron transfer
      from outer membrane c-Cyts of cells to the electrode surface. Lactic acid, formic
      acid and cyclodextrin produced lower quantity of electric charge of 10.13 C, 9.83
      C and 10.10 C, the corresponding OD600 value was 0.180, 0.286 and 0.152 in BES;
      while galactose, arabinose and glucose generated higher quantity of electric
      charge of 12.34 C, 13.42 C and 17.45 C, and increased OD600 values were 0.338,
      0.558 and 0.409 in BES. SEMs results showed that plenty of plump and stretched
      cells as well as appendages were observed when lactic acid, formic acid, and
      cyclodextrin were utilized as substrates, while sparse cells in short shape were
      obtained when galactose, arabinose and glucose were used as substrates.
      CONCLUSIONS: These results suggest that substrate not only has important role in
      electrochemical performances of MFCs but also in biological properties of
      electricigens. Lactic acid, formic acid, and cyclodextrin beneficial for cell
      growth under aerobic conditions are unfavourable for planktonic cell growth and
      current generation under anaerobic conditions, while consumptions of galactose,
      arabinose and glucose adverse to cell growth under aerobic conditions are
      favourable for planktonic cell growth and current generation under anaerobic
      conditions due to the increase of cell numbers with more outer membrane c-Cyts
      transferring electrons between the electrode surface and cells.

PMID- 24885729
TI  - The protocol for the Families First Edmonton trial (FFE): a randomized community
      based trial to compare four service integration approaches for families with low
      income.
AB  - BACKGROUND: Families with low incomes experience an array of health and social
      challenges that compromise their resilience and lead to negative family outcomes.
      Along with financial constraints, there are barriers associated with mental and
      physical health, poorer education and language. In addition, vulnerable
      populations experience many services as markedly unhelpful. This combination of
      family and service barriers results in reduced opportunities for effective,
      primary-level services and an increased use of more expensive secondary-level
      services (e.g., emergency room visits, child apprehensions, police involvement).
      A systematic review of effective interventions demonstrated that promotion of
      physical and mental health using existing service was critically important.
      METHODS/DESIGN: The Families First Edmonton Trial (FFE) tests four service
      integration approaches to increase use of available health and social services
      for families with low-income. It is a randomized, two-factor, single-blind,
      longitudinal effectiveness trial where low-income families (1168) were randomly
      assigned to receive either (1) Family Healthy Lifestyle plus Family Recreation
      service integration (Comprehensive), (2) Family Healthy Lifestyle service
      integration, (3) Family Recreation service integration, or (4) existing services.
      To be eligible families needed to be receiving one of five government income
      assistance programs. The trial was conducted in the City of Edmonton between
      January 2006 and August 2011. The families were followed for a total of three
      years of which interventional services were received for between 18 and 24
      months. The primary outcome is the number of family linkages to health and social
      services as measured by a customized survey tool "Family Services Inventory".
      Secondary outcomes include type and satisfaction with services, cost of services,
      family member health, and family functioning. Where possible, the measures for
      secondary outcomes were selected because of their standardization, the presence
      of published norming data, and their utility as comparators to other studies of
      low-income families. As an effectiveness trial, community and government partners
      participated in all committees through a mutually agreed upon governance model
      and helped manage and problem solve with researchers. DISCUSSION: Modifications
      were made to the FFE trial based on the pragmatics of community-based trials.
      TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00705328.

PMID- 24885730
TI  - The early response of renal cell carcinoma to tyrosine kinase inhibitors
      evaluated by FDG PET/CT was not influenced by metastatic organ.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKIs) have become the mainstay of
      treatment for advanced renal cell carcinoma (RCC), but it has been unclear
      whether the antitumor effect of TKIs depends on the organ where the RCC
      metastasis is located. We previously reported that the FDG accumulation assessed
      by FDG PET/CT, was a powerful index for evaluating the biological response to
      TKI. In this study we investigated the differences in FDG accumulation and the
      response to TKI as assessed by FDG PET/CT among various organs where RCC were
      located. METHODS: A total of 48 patients with advanced RCC treated with a TKI (25
      with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at
      1 month after a TKI treatment initiation. The maximum standardized uptake value
      (SUVmax) of all RCC lesions were measured and analyzed. RESULTS: We evaluated 190
      RCC lesions. The pretreatment SUVmax values (mean +/- SD) were as follows: in the
      49 lung metastases, 4.1 +/- 3.3; in the 40 bone metastases, 5.4 +/- 1.6; in the
      37 lymph node metastases, 6.7 +/- 2.7; in the 29 abdominal parenchymal organ
      metastases, 6.6 +/- 2.7; in the 26 muscle or soft tissue metastases, 4.4 +/- 2.6;
      and in the nine primary lesions, 8.9 +/- 3.9. Significant differences in the
      SUVmax were revealed between metastases and primary lesions (p = 0.006) and
      between lung metastases and non-lung metastases (p < 0.001). The SUVmax change
      ratios at 1 month after TKI treatment started were -14.2 +/- 48.4% in the lung
      metastases, -10.4 +/- 23.3% in the bone metastases, -9.3 +/- 47.4% in the lymph
      node metastases, -24.5 +/- 41.7% in the abdominal parenchymal organ metastases, 
      10.6 +/- 47.4% in the muscle or soft tissue metastases, and -24.2 +/- 18.3% in
      the primary lesions. There was no significant difference among the organs (p =
      0.531). CONCLUSIONS: The decrease ratio of FDG accumulation of RCC lesions
      evaluated by PET/CT at 1 month after TKI treatment initiation was not influenced
      by the organs where the RCC metastasis was located. This result suggests that
      TKIs can be used to treat patients with advanced RCC regardless of the metastatic
      site.

PMID- 24885731
TI  - Development of late blight resistant potatoes by cisgene stacking.
AB  - BACKGROUND: Phytophthora infestans, causing late blight in potato, remains one of
      the most devastating pathogens in potato production and late blight resistance is
      a top priority in potato breeding. The introduction of multiple resistance (R)
      genes with different spectra from crossable species into potato varieties is
      required. Cisgenesis is a promising approach that introduces native genes from
      the crops own gene pool using GM technology, thereby retaining favourable
      characteristics of established varieties. RESULTS: We pursued a cisgenesis
      approach to introduce two broad spectrum potato late blight R genes, Rpi-sto1 and
      Rpi-vnt1.1 from the crossable species Solanum stoloniferum and Solanum venturii,
      respectively, into three different potato varieties. First, single R gene
      containing transgenic plants were produced for all varieties to be used as
      references for the resistance levels and spectra to be expected in the respective
      genetic backgrounds. Next, a construct containing both cisgenic late blight R
      genes (Rpi-vnt1.1 and Rpi-sto1), but lacking the bacterial kanamycin resistance
      selection marker (NPTII) was transformed to the three selected potato varieties
      using Agrobacterium-mediated transformation. Gene transfer events were selected
      by PCR among regenerated shoots. Through further analyses involving morphological
      evaluations in the greenhouse, responsiveness to Avr genes and late blight
      resistance in detached leaf assays, the selection was narrowed down to eight
      independent events. These cisgenic events were selected because they showed broad
      spectrum late blight resistance due to the activity of both introduced R genes.
      The marker-free transformation was compared to kanamycin resistance assisted
      transformation in terms of T-DNA and vector backbone integration frequency. Also,
      differences in regeneration time and genotype dependency were evaluated.
      CONCLUSIONS: We developed a marker-free transformation pipeline to select potato
      plants functionally expressing a stack of late blight R genes. Marker-free
      transformation is less genotype dependent and less prone to vector backbone
      integration as compared to marker-assisted transformation. Thereby, this study
      provides an important tool for the successful deployment of R genes in
      agriculture and contributes to the production of potentially durable late blight
      resistant potatoes.

PMID- 24885732
TI  - Mental health and wellbeing in spouses of persons with dementia: the Nord
      Trondelag Health Study.
AB  - BACKGROUND: Caring for a spouse diagnosed with dementia can be a stressful
      situation and can put the caregiving partner at risk of loss of mental health and
      wellbeing. The main aim of this study was to investigate the relationship between
      dementia and spousal mental health in a population-based sample of married
      couples older than 55 years of age. The association was investigated for
      individuals living together with their demented partner, as well as for
      individuals whose demented partner was living in an institution. METHODS: Data on
      dementia were collected from hospitals and nursing homes in the county of Nord
      Trondelag, Norway. These data were combined with data on spousal mental health,
      which were collected in a population-based health screening: the Nord-Trondelag
      Health Study (HUNT). Of 6,951 participating couples (>55 years), 131 included one
      partner that had been diagnosed with dementia. RESULTS: Our results indicate that
      after adjustment for covariates, having a partner with dementia is associated
      with lower levels of life satisfaction and more symptoms of anxiety and
      depression than reported by spouses of elderly individuals without dementia.
      Spouses living together with a partner diagnosed with dementia experienced
      moderately lower levels of life satisfaction (0.35 standard deviation [SD]) and
      more symptoms of depression (0.38 SD) and anxiety (0.23 SD) than did their non
      caregiving counterparts. Having a partner with dementia that resided in a nursing
      home was associated with clearly lower life satisfaction. Compared with non
      caregivers, these spouses reported lower levels of life satisfaction (1.16 SD),
      and also more symptoms of depression (0.38 SD), and more symptoms of anxiety
      (0.42 SD). CONCLUSIONS: Having a partner with dementia is associated with loss of
      mental health and reduced life satisfaction. The risk of adverse mental health
      outcomes is greatest after the partner's nursing home admission.

PMID- 24885733
TI  - In vitro biodegradation of cyanotoxins in the rumen fluid of cattle.
AB  - BACKGROUND: In countries around the Baltic Sea grazing ruminants have access to
      and drink, surface water from lakes, rivers and in several coastal regions. The
      water quality of these naturally occurring reservoirs affects performance and
      health of livestock. In the Baltic Sea both microcystin (MC) and nodularin (NOD)
      occurs as cyclic peptides and have hepatotoxic effects. Although cattle obviously
      have died after consuming contaminated water very little information is available
      as to how susceptible ruminants are to the toxins produced by cyanobacteria. The
      critical question as to whether the rumen microflora might constitute a
      protective shield is unresolved. For this reason our aim is to investigate a
      possible degradation rate of these toxins in rumen. RESULTS: The ability of rumen
      microorganisms to degrade certain important cyanotoxins (MC-LR, YR, RR and NOD)
      was studied in vitro by incubating with rumen fluid at three different
      concentrations (0.05, 0.5 and 5 MUg/mL) for 3 h. The degradation efficiencies
      were determined by LC-MS (ESI) positive mode. Degradation was observed in the
      following order MC-RR 36%, NOD 35%, MC-RR 25% and MC-LR 8.9% at lower
      concentrations within 3 h. However, average degradation was observed at
      concentration of 0.5 MUg/mL. No degradation was observed in higher concentrations
      for entire 3 h. The present results reveal that the degradation was both dose and
      time dependent. CONCLUSIONS: In conclusion the present results suggest that the
      rumen microbial flora may protect ruminants from being intoxicated by
      Cyanotoxins.

PMID- 24885734
TI  - Private haplotypes can reveal local adaptation.
AB  - BACKGROUND: Genome-wide scans for regions that demonstrate deviating patterns of
      genetic variation have become common approaches for finding genes targeted by
      selection. Several genomic patterns have been utilized for this purpose,
      including deviations in haplotype homozygosity, frequency spectra and genetic
      differentiation between populations. RESULTS: We describe a novel approach based
      on the Maximum Frequency of Private Haplotypes--MFPH--to search for signals of
      recent population-specific selection. The MFPH statistic is straightforward to
      compute for phased SNP- and sequence-data. Using both simulated and empirical
      data, we show that MFPH can be a powerful statistic to detect recent population
      specific selection, that it performs at the same level as other commonly used
      summary statistics (e.g. FST, iHS and XP-EHH), and that MFPH in some cases
      capture signals of selection that are missed by other statistics. For instance,
      in the Maasai, MFPH reveals a strong signal of selection in a region where other
      investigated statistics fail to pick up a clear signal that contains the genes
      DOCK3, MAPKAPK3 and CISH. This region has been suggested to affect height in many
      populations based on phenotype-genotype association studies. It has specifically
      been suggested to be targeted by selection in Pygmy groups, which are on the
      opposite end of the human height spectrum compared to the Maasai. CONCLUSIONS:
      From the analysis of both simulated and publicly available empirical data, we
      show that MFPH represents a summary statistic that can provide further insight
      concerning population-specific adaptation.

PMID- 24885735
TI  - A school-based rope skipping intervention for adolescents in Hong Kong: protocol
      of a matched-pair cluster randomized controlled trial.
AB  - BACKGROUND: Schools present venues for physical activity promotion among youth,
      with physical education (PE) considered the primary vehicle responsible for
      increasing activity levels. Yet students are not very physically active during
      typical school PE classes. With the aim to engage Hong Kong students in more
      moderate-to-vigorous physical activity (MVPA) during PE, a fitness infusion
      intervention using rope skipping was designed, and its effectiveness will be
      examined. Rope skipping was chosen because a) it provides moderate-to-high
      intensity physical activity; b) is inexpensive; c) students find it enjoyable;
      and d) is feasible in typical environments in Hong Kong, where PE classes are
      large in size (up to 40 students) and space available for physical activity is
      usually limited. METHODS/DESIGN: A matched-pair cluster randomized controlled
      trial was designed. Secondary school students from 24 classes (from 12 schools)
      will be recruited to participate in the trial. Students' baseline MVPA will be
      measured during school PE. Classes will be matched according to baseline
      variables and one class from each pair will be randomized into the experimental
      group. Teachers in the experimental group will be invited to attend a teacher
      workshop, and will insert a 15-minute rope skipping activity in four consecutive
      PE lessons. Motivational factors based on self-determination theory will also be
      measured as secondary outcomes. The effectiveness of the intervention will be
      evaluated by comparing changes in the proportion of lesson time spent in MVPA
      from baseline to follow-up across the experimental and control groups.
      DISCUSSION: Physical activity levels in PE are often very low and there is a need
      to identify feasible low-cost interventions that can be easily disseminated. If
      the results of the study suggest the intervention to be effective, it could be
      implemented to schools throughout Hong Kong and other cities where space is
      limited. TRAIL REGISTRATION ANZCTR: ACTRN12613000968774. Registered on 30 August
      2013.

PMID- 24885736
TI  - Characterization of monocarboxylate transporters (MCTs) expression in soft tissue
      sarcomas: distinct prognostic impact of MCT1 sub-cellular localization.
AB  - BACKGROUND: Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite
      current therapeutic advances, still confer a poor outcome to half of the
      patients. As other solid tumors, STSs exhibit high glucose consumption rates,
      associated with worse prognosis and therapeutic response. As highly glycolytic
      tumors, we hypothesized that sarcomas should present an increased expression of
      lactate transporters (MCTs). METHODS: Immunohistochemical expression of MCT1,
      MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression
      profiles were associated with patients' clinical-pathological parameters.
      RESULTS: MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of
      cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was
      conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1
      nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in
      the plasma membrane, were associated with poor prognostic variables including
      high tumor grade, disease progression and shorter overall survival. Conversely,
      we found MCT1 nuclear expression to be associated with low grade tumors and
      longer overall survival. CONCLUSIONS: The present work represents the first
      report of MCTs characterization in STSs. We showed the original finding of MCT1
      expression in the nucleus. Importantly, opposite biological roles should be
      behind the dual sub-cellular localization of MCT1, as plasma membrane expression
      of MCT1 is associated with worse patients' prognosis, while nuclear expression is
      associated with better prognosis.

PMID- 24885737
TI  - Lessons from the implementation of LLIN distribution campaign in Ilorin Kwara
      State, Nigeria.
AB  - BACKGROUND: Studies implemented to evaluate the success of Long-lasting
      insecticidal nets (LLIN) distribution campaigns are often limited to ownership
      and utilization rates, neglecting other factors that directly affect the efficacy
      of the tool in malaria control. This study investigates sleeping habits and net
      maintenance behaviour in addition to LLIN ownership, utilization and the
      challenges associated with LLIN use among residents in Ilorin City where the tool
      has been massively distributed. METHODS: A cross-sectional survey was conducted
      using pre-tested interviewer-administered questionnaire to obtain information
      from randomly selected household respondents in Ilorin, the Kwara State Capital.
      The study was conducted in July 2012, about sixteen months after the March 2011
      distribution of LLIN in the locality. The results were analyzed using the EPI
      INFO 2007 version. RESULTS: LLIN ownership (85%) and utilization (37%) rates
      improved compared to earlier reports, though 29% of net users have noticed holes
      in the nets even as 26% claimed to have actually experienced mosquito bites under
      it. Most (92%) of the respondents who slept under LLIN the previous night before
      the study spent the first five hours of the night (19.00-23.00 hr) outdoors while
      88% also engage in inappropriate net washing practices. All the LLIN users
      claimed to have experienced at least one malaria episode while 43% have had two
      or more episodes within the past twelve months. CONCLUSION: The use of LLIN among
      the respondents in this study was accompanied by chancy sleeping habits,
      inappropriate net maintenance practices and repeated experience of mosquito bites
      under the nets. This shows the need to sustain the will and confidence of LLIN
      users in this area through frequent monitoring and surveillance visits targeted
      at enlightening the people on habits that increase malaria exposure risks as well
      as proper use and maintenance of LLIN for maximum malaria vector control
      benefits.

PMID- 24885738
TI  - Black, queer, and looking for a job: an exploratory study of career decision
      making among self-identified sexual minorities at an urban historically black
      college/university.
AB  - This thematically analyzed study seeks to explore the career decision perceptions
      of sexual minority college students at an urban historically black
      college/university (HBCU). This qualitative focus group study delved into how
      sexual minorities feel their visible variables of race, gender expression, and
      degree of disclosure influence their career thought process. Theories relative to
      the study included Krumboltz's social learning theory of career decision-making,
      gender role theory, racial socialization, Cass's homosexual identity model, and
      impression management. Though participants initially proclaimed they did not
      allow their sexual minority identity to affect their career decisions, their
      overall responses indicated otherwise. 

PMID- 24885739
TI  - Factors associated with pre-marital sexual debut among unmarried high school
      female students in bahir Dar town, Ethiopia: cross- sectional study.
AB  - BACKGROUND: Pre-marital sexual debut increase the risk of sexually transmitted
      infections (STIs) including HIV/AIDS and unwanted pregnancy. It may also affect
      their school performance and completion rate. In spite of this fact, number of
      unmarried female students who started sexual debut is increasing from time to
      time. However, information on the extent of pre-marital sexual debut and
      associated factors were not well studied and documented in the study area where
      pre-marital sexual debut is largely condemned. Therefore this study was conducted
      to assess the magnitude and associated factors of pre-marital sexual debut.
      METHODS: School based cross-sectional survey was conducted from May 10-13/2012. A
      total of 1123 unmarried high school female students were selected by multi- stage
      sampling technique. Data were collected using structured, self administered
      questionnaire. Descriptive statistics, binary and multivariable logistic
      regression analyses were used to identify factors associated with pre-marital
      sexual debut. RESULTS: Among unmarried high school female students 30.8% reported
      pre-marital sexual debut. The major associated factors were frequent watching of
      pornographic video [AOR = 10.15, 95% CI: (6.63, 15.53)], peer pressure [AOR =
      2.98, 95% CI: (1.57, 5.67)] and chewing khat [AOR = 8.99, 95% CI: (3.84, 21.06)].
      CONCLUSION: Significant proportion of unmarried high school female students have
      started pre-marital sexual debut. The finding suggests the need for communicating
      and supporting school students to help them make informed and safer decisions on
      their sexual behavior. Therefore, Bahir dar city administration health and
      education bureau should design persistent and effective health education to
      decrease pre-marital sexual debut in unmarried female students.

PMID- 24885740
TI  - Becoming a medical educator: motivation, socialisation and navigation.
AB  - BACKGROUND: Despite an increasing concern about a future shortage of medical
      educators, little published research exists on career choices in medical
      education nor the impact of specific training posts in medical education (e.g.
      academic registrar/resident positions). Medical educators at all levels, from
      both medical and non-medical backgrounds, are crucial for the training of medical
      students, junior doctors and in continuing professional development. We explored
      the motivations and experiences of junior doctors considering an education career
      and undertaking a medical education registrar (MER) post. METHODS: Data were
      collected through semi-structured interviews with junior doctors and clinicians
      across Queensland Health. Framework analysis was used to identify themes in the
      data, based on our defined research questions and the medical education workforce
      issues prompting the study. We applied socio-cognitive career theory to guide our
      analysis and to explore the experience of junior doctors in medical education
      registrar posts as they enter, navigate and fulfil the role. RESULTS: We
      identified six key themes in the data: motivation for career choice and wanting
      to provide better education; personal goals, expectations and the need for self
      direction; the influence of role models; defining one's identity; support
      networks and the need for research as a potential barrier to pursuing a career
      in/with education. We also identified the similarities and differences between
      the MERs' experiences to develop a composite of an MER's journey through career
      choice, experience in role and outcomes. CONCLUSIONS: There is growing interest
      from junior doctors in pursuing education pathways in a clinical environment.
      They want to enhance clinical teaching in the hospitals and become specialists
      with an interest in education, and have no particular interest in research or
      academia. This has implications for the recruitment and training of the next
      generation of clinical educators.

PMID- 24885741
TI  - Improved lag screw positioning in the treatment of proximal femur fractures using
      a novel computer assisted surgery method: a cadaveric study.
AB  - BACKGROUND: The importance of the tip-apex distance (TAD) to predict the cut-out
      risk of fixed angle hip implants has been widely discussed in the scientific
      literature. Intra-operative determination of TAD is difficult and can be hampered
      by image quality, body habitus, and image projection. The purpose of this paper
      is to evaluate, through a cadaveric study, a novel computer assisted surgery
      system (ADAPT), which is intended for intraoperative optimisation of lag screw
      positioning during antegrade femoral nailing. A 3D measure for optimal lag screw
      position, the tip-to-head-surface distance (TSD), is introduced. METHODS: 45
      intra-medullary hip screw procedures were performed by experienced and less
      experienced surgeons in a cadaveric test series: in 23 surgeries the ADAPT system
      was used, and in 22 it was not used. The position of the lag screw within the
      femoral head and neck was evaluated using post-operative CT scans. TAD, TSD,
      fluoroscopy as well as procedure time and variability were assessed. RESULTS: The
      use of the ADAPT system increased accuracy in TSD values (i.e. smaller
      variability around the target value) for both groups of surgeons (interquartile
      range (IQR) of experienced surgeons: 4.10 mm (Conventional) vs. 1.35 mm (ADAPT)
      (p = 0.004)/IQR of less experienced surgeons: 3.60 mm (Conventional) vs. 0.85 mm
      (ADAPT) (p = 0.002)). The accuracy gain in TAD values did not prove to be
      significant in the grouped analysis (p = 0.269 for experienced surgeons; p =
      0.066 for less experienced surgeons); however, the overall analysis showed a
      significant increase in accuracy (IQR: 4.50 mm (Conventional) vs. 2.00 mm (ADAPT)
      (p = 0.042)). The fluoroscopy time was significantly decreased by the use of the
      ADAPT system with a median value of 29.00 seconds (Conventional) vs. 17.00
      seconds (ADAPT) for the less experienced surgeons (p = 0.046). There was no
      statistically significant impact on the procedure time (p = 0.739). CONCLUSIONS:
      The ADAPT system improved the position of the lag screw within the femoral head,
      regardless of the surgeon's level of clinical experience, and at the same time
      decreased overall fluoroscopy usage. These positive effects are achieved without
      increasing procedure time.

PMID- 24885742
TI  - Nutritional status, growth and disease management in children with single and
      dual diagnosis of type 1 diabetes mellitus and coeliac disease.
AB  - BACKGROUND: The consequences of subclinical coeliac disease (CD) in Type 1
      diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and
      disease management in children with dual diagnosis (T1DM + CD) before and after
      CD diagnosis. METHODS: Anthropometry, glycated haemoglobin (HbA1c) and IgA tissue
      transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23
      children with T1DM + CD. This group was matched for demographics, T1DM duration,
      age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls. RESULTS:
      No differences in growth or anthropometry were found between children with T1DM +
      CD and controls at any time point. Children with T1DM + CD, had higher BMI z
      score two years prior to, than at CD diagnosis (p < 0.001). BMI z-score change
      one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p
      = 0.009). At two years, height velocity and change in BMI z-scores were similar
      in all groups. No differences were observed in HbA1c between the T1DM + CD and
      T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised
      tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM
      + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p < 0.001); by two years there
      was no difference. CONCLUSIONS: No major nutrition or growth deficits were
      observed in children with T1DM + CD. CD diagnosis does not impact on T1DM
      glycaemic control. CD specific serology was comparable to children with single
      CD, but those with dual diagnosis may need more time to adjust to gluten free
      diet.

PMID- 24885743
TI  - Chronic unpredictable mild stress combined with a high-fat diets aggravates
      atherosclerosis in rats.
AB  - BACKGROUND: Depression and high-fat diet are both known as independent risk
      factors for atherosclerosis and other cardiovascular diseases, suggesting the
      interaction of psychological and physiological factors in the development of
      these diseases. The liver is a crucial organ that facilitate lipid metabolism
      especially in reverse cholesterol transport (RCT), while according to the theory
      of Traditional Chinese Medicine, depression as a kind of psychological stress has
      an influence on hepatic function. So there seem to be some links between
      depression and lipid metabolic disorders. METHODS: To investigate these links, we
      separately treated rats with chronic unpredictable mild stress (CMS) and/or a
      high-fat diet (HD) to evaluate the development of atherosclerosis and the
      expression of hepatic ABCG8, ABCG5, SR-BI, CYP7A1, LXRalpha, and LCAT which were
      associated with reverse cholesterol transport. RESULTS: This study provided
      evidence that high-fat diet greatly decreased these genes expression related to
      RCT while chronic stress alone tended to promote RCT. Chronic unpredictable mild
      stress combined with a high-fat diet attenuated RCT and aggravated atherogenesis.
      CONCLUSIONS: These observations suggested that chronic psychological stress alone
      is virtually propitious to lipid metabolism, however when under a condition of
      high-fat diet, it deteriorated atherosclerotic plague and did harm to RCT.

PMID- 24885744
TI  - Relationship of redundant Th17 cells and IL-17A, but not IL-17 F, with the
      severity of obstructive sleep apnoea/hypopnoea syndrome (OSAHS).
AB  - BACKGROUND: The pathogenesis of obstructive sleep apnoea/hypopnoea syndrome
      (OSAHS), a highly prevalent disease, is not completely understood. The purpose of
      this study was to investigate the contributions of Th17 cells and the Th17
      associated cytokines IL-17A and IL-17 F to OSAHS. METHODS: 46 male patients with
      a clinical suspicion of OSAHS were enrolled and divided into four groups based on
      their polysomnography results: controls and mild, moderate, and severe OSAHS. The
      serum levels of IL-17A and IL-17 F were determined by enzyme linked immunosorbent
      assay (ELISA), pulmonary arterial pressure (PAP) was determined by
      echocardiography, and Th17 cell frequencies in peripheral blood were measured by
      flow cytometry. RESULTS: Serum IL-17A levels in the severe group were elevated
      (median value: control group 0.89 pg/ml, mild OSAHS 1.02 pg/ml, moderate OSAHS
      1.18 pg/ml, and severe OSAHS 1.62 pg/ml; p < 0.05) and positively correlated with
      AHI (r = 0.52, p < 0.05) but negatively related to the mean O2 saturation and
      lowest O2 saturation (r = -0.349, p < 0.05; and r = -0.336, p < 0.05,
      respectively). Although the frequencies of Th17 cells in the OSAHS groups were
      higher than that in the control group, these differences were not significant (p
      = 0.275). Pulmonary arterial hypertension was not present in our patients as the
      median PAP of the normal control and the mild, moderate, and severe OSAHS groups
      were 26, 27.5, 24.5, and 25.5 mmHg, respectively (p = 0.676). CONCLUSION: IL-17A
      may be involved in the pathogenesis of OSAHS and may represent a target for
      therapeutic intervention.

PMID- 24885746
TI  - Facilitating professional liaison in collaborative care for depression in UK
      primary care; a qualitative study utilising normalisation process theory.
AB  - BACKGROUND: Collaborative care (CC) is an organisational framework which
      facilitates the delivery of a mental health intervention to patients by case
      managers in collaboration with more senior health professionals (supervisors and
      GPs), and is effective for the management of depression in primary care. However,
      there remains limited evidence on how to successfully implement this
      collaborative approach in UK primary care. This study aimed to explore to what
      extent CC impacts on professional working relationships, and if CC for depression
      could be implemented as routine in the primary care setting. METHODS: This
      qualitative study explored perspectives of the 6 case managers (CMs), 5
      supervisors (trial research team members) and 15 general practitioners (GPs) from
      practices participating in a randomised controlled trial of CC for depression.
      Interviews were transcribed verbatim and data was analysed using a two-step
      approach using an initial thematic analysis, and a secondary analysis using the
      Normalisation Process Theory concepts of coherence, cognitive participation,
      collective action and reflexive monitoring with respect to the implementation of
      CC in primary care. RESULTS: Supervisors and CMs demonstrated coherence in their
      understanding of CC, and consequently reported good levels of cognitive
      participation and collective action regarding delivering and supervising the
      intervention. GPs interviewed showed limited understanding of the CC framework,
      and reported limited collaboration with CMs: barriers to collaboration were
      identified. All participants identified the potential or experienced benefits of
      a collaborative approach to depression management and were able to discuss ways
      in which collaboration can be facilitated. CONCLUSION: Primary care professionals
      in this study valued the potential for collaboration, but GPs' understanding of
      CC and organisational barriers hindered opportunities for communication. Further
      work is needed to address these organisational barriers in order to facilitate
      collaboration around individual patients with depression, including shared IT
      systems, facilitating opportunities for informal discussion and building in
      formal collaboration into the CC framework. TRIAL REGISTRATION: ISRCTN32829227
      30/9/2008.

PMID- 24885745
TI  - Total-body irradiation produces late degenerative joint damage in rats.
AB  - PURPOSE: Premature musculoskeletal joint failure is a major source of morbidity
      among childhood cancer survivors. Radiation effects on synovial joint tissues of
      the skeleton are poorly understood. Our goal was to assess long-term changes in
      the knee joint from skeletally mature rats that received total-body irradiation
      while skeletal growth was ongoing. MATERIALS AND METHODS: 14 week-old rats were
      irradiated with 1, 3 or 7 Gy total-body doses of 18 MV X-rays. At 53 weeks of
      age, structural and compositional changes in knee joint tissues (articular
      cartilage, subchondral bone, and trabecular bone) were characterized using 7T
      MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and
      histology. RESULTS: T2 relaxation times of the articular cartilage were lower
      after exposure to all doses. Likewise, calcifications were observed in the
      articular cartilage. Trabecular bone microarchitecture was compromised in the
      tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3
      and 7 Gy rats. CONCLUSIONS: Late degenerative changes in articular cartilage and
      bone were observed after total-body irradiation in adult rats exposed prior to
      skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential
      prognostic indicators of late radiation-induced joint damage.

PMID- 24885747
TI  - First report of Cryptosporidium spp. in white yaks in China.
AB  - BACKGROUND: Cryptosporidium is an enteric apicomplexan parasite, which can infect
      yaks, leading to reduction of milk production and poor weight gain. White yak
      (Bos grunniens) is a unique yak breed inhabiting only in Tianzhu Tibetan
      Autonomous County, Gansu province, northwestern China. The objective of the
      present study was to molecularly determine Cryptosporidium infection and species
      in white yaks. FINDINGS: Seventy-six fecal samples from white yaks in Tianzhu
      Tibetan Autonomous County, Gansu province were collected. The small subunit
      ribosomal RNA (SSU rRNA) gene of each sample was amplified using nested PCR and
      sequenced. The Cryptosporidium species was determined by comparison of the
      obtained sequences with that of corresponding Cryptosporidium sequences available
      in GenBank by BLAST (http://www.ncbi.nlm.nih.gov/BLAST/) and phylogenetic
      analysis with maximum likelihood (ML) using PAUP*. The overall prevalence of
      Cryptosporidium infection in white yak was 5.26% (4/76). Species identification
      showed C. andersoni in one sample (collected in September), and C. bovis in three
      samples (one collected in November and two collected in September). CONCLUSIONS:
      The present investigation revealed the existence of Cryptosporidium infection in
      white yaks in China, for the first time, and two Cryptosporidium species, namely
      C. andersoni and C. bovis, were identified. These findings extend the host range
      for Cryptosporidium spp., and also provide base-line information for further
      studies of molecular epidemiology and control of Cryptosporidium infection in the
      unique white yaks.

PMID- 24885749
TI  - Study of mandible reconstruction using a fibula flap with application of additive
      manufacturing technology.
AB  - BACKGROUND: This study aimed to establish surgical guiding techniques for
      completing mandible lesion resection and reconstruction of the mandible defect
      area with fibula sections in one surgery by applying additive manufacturing
      technology, which can reduce the surgical duration and enhance the surgical
      accuracy and success rate. METHODS: A computer assisted mandible reconstruction
      planning (CAMRP) program was used to calculate the optimal cutting length and
      number of fibula pieces and design the fixtures for mandible cutting,
      registration, and arrangement of the fibula segments. The mandible cutting and
      registering fixtures were then generated using an additive manufacturing system.
      The CAMRP calculated the optimal fibula cutting length and number of segments
      based on the location and length of the defective portion of the mandible. The
      mandible cutting jig was generated according to the boundary surface of the
      lesion resection on the mandible STL model. The fibular cutting fixture was based
      on the length of each segment, and the registered fixture was used to quickly
      arrange the fibula pieces into the shape of the defect area. In this study, the
      mandibular lesion was reconstructed using registered fibular sections in one
      step, and the method is very easy to perform. RESULTS AND CONCLUSION: The
      application of additive manufacturing technology provided customized models and
      the cutting fixtures and registered fixtures, which can improve the efficiency of
      clinical application. This study showed that the cutting fixture helped to
      rapidly complete lesion resection and fibula cutting, and the registered fixture
      enabled arrangement of the fibula pieces and allowed completion of the mandible
      reconstruction in a timely manner. Our method can overcome the disadvantages of
      traditional surgery, which requires a long and different course of treatment and
      is liable to cause error. With the help of optimal cutting planning by the CAMRP
      and the 3D printed mandible resection jig and fibula cutting fixture, this all-in
      one process of mandible reconstruction furnishes many benefits in this field by
      enhancing the accuracy of surgery, shortening the operation duration, reducing
      the surgical risk, and resulting in a better mandible appearance of the patients
      after surgery.

PMID- 24885748
TI  - From mouth to macrophage: mechanisms of innate immune subversion by Mycobacterium
      avium subsp. paratuberculosis.
AB  - Johne's disease (JD) is a chronic enteric infection of cattle caused by
      Mycobacterium avium subsp. paratuberculosis (MAP). The high economic cost and
      potential zoonotic threat of JD have driven efforts to develop tools and
      approaches to effectively manage this disease within livestock herds. Efforts to
      control JD through traditional animal management practices are complicated by
      MAP's ability to cause long-term environmental contamination as well as
      difficulties associated with diagnosis of JD in the pre-clinical stages. As such,
      there is particular emphasis on the development of an effective vaccine. This is
      a daunting challenge, in large part due to MAP's ability to subvert protective
      host immune responses. Accordingly, there is a priority to understand MAP's
      interaction with the bovine host: this may inform rational targets and approaches
      for therapeutic intervention. Here we review the early host defenses encountered
      by MAP and the strategies employed by the pathogen to avert or subvert these
      responses, during the critical period between ingestion and the establishment of
      persistent infection in macrophages.

PMID- 24885750
TI  - Combining calls from multiple somatic mutation-callers.
AB  - BACKGROUND: Accurate somatic mutation-calling is essential for insightful
      mutation analyses in cancer studies. Several mutation-callers are publicly
      available and more are likely to appear. Nonetheless, mutation-calling is still
      challenging and there is unlikely to be one established caller that
      systematically outperforms all others. Therefore, fully utilizing multiple
      callers can be a powerful way to construct a list of final calls for one's
      research. RESULTS: Using a set of mutations from multiple callers that are
      impartially validated, we present a statistical approach for building a combined
      caller, which can be applied to combine calls in a wider dataset generated using
      a similar protocol. Using the mutation outputs and the validation data from The
      Cancer Genome Atlas endometrial study (6,746 sites), we demonstrate how to build
      a statistical model that predicts the probability of each call being a somatic
      mutation, based on the detection status of multiple callers and a few associated
      features. CONCLUSION: The approach allows us to build a combined caller across
      the full range of stringency levels, which outperforms all of the individual
      callers.

PMID- 24885751
TI  - Using logic model methods in systematic review synthesis: describing complex
      pathways in referral management interventions.
AB  - BACKGROUND: There is increasing interest in innovative methods to carry out
      systematic reviews of complex interventions. Theory-based approaches, such as
      logic models, have been suggested as a means of providing additional insights
      beyond that obtained via conventional review methods. METHODS: This paper reports
      the use of an innovative method which combines systematic review processes with
      logic model techniques to synthesise a broad range of literature. The potential
      value of the model produced was explored with stakeholders. RESULTS: The review
      identified 295 papers that met the inclusion criteria. The papers consisted of
      141 intervention studies and 154 non-intervention quantitative and qualitative
      articles. A logic model was systematically built from these studies. The model
      outlines interventions, short term outcomes, moderating and mediating factors and
      long term demand management outcomes and impacts. Interventions were grouped into
      typologies of practitioner education, process change, system change, and patient
      intervention. Short-term outcomes identified that may result from these
      interventions were changed physician or patient knowledge, beliefs or attitudes
      and also interventions related to changed doctor-patient interaction. A range of
      factors which may influence whether these outcomes lead to long term change were
      detailed. Demand management outcomes and intended impacts included content of
      referral, rate of referral, and doctor or patient satisfaction. CONCLUSIONS: The
      logic model details evidence and assumptions underpinning the complex pathway
      from interventions to demand management impact. The method offers a useful
      addition to systematic review methodologies. TRIAL REGISTRATION NUMBER: PROSPERO
      registration number: CRD42013004037.

PMID- 24885753
TI  - Safety and efficacy of the PleurX catheter for the treatment of malignant
      ascites.
AB  - BACKGROUND: Malignant ascites is a common complication seen in association with
      various types of neoplastic processes. Due to high recurrence rates, patients may
      require multiple paracenteses, which have associated complications such as
      increased risk of bleeding, infection, pain, and volume and electrolyte
      depletion. OBJECTIVE: This study evaluated the management of malignant ascites by
      placement of the PleurX(r) tunneled catheter system at a single center. METHODS:
      This was a retrospective study of 38 patients who underwent PleurX catheter
      placement for refractory malignant ascites between February 2006 and March 2012
      at our institution. Pretreatment characteristics and outcome measures were
      reported using descriptive statistics. RESULTS: The population included 21 males
      and 17 females with a mean age of 60.6 years (range, 36-79 years) diagnosed with
      metastatic disease from a variety of primary malignancies, the most common of
      which was pancreatic cancer (10 patients). In 84% of patients (32/38) who were
      not lost to follow-up, mean survival time was 40.7 days (range 4-434 days).
      Technical success rate of catheter placement was 100%. CONCLUSIONS: The PleurX
      catheter can be used to manage malignant ascites in severely ill patients with
      metastatic cancer, with a high rate of procedural success and a low incidence of
      potentially serious adverse events, infections, or catheter-related
      complications.

PMID- 24885754
TI  - A kinetic fluorescence assay reveals unusual features of Ca++ uptake in
      Plasmodium falciparum-infected erythrocytes.
AB  - BACKGROUND: To facilitate development within erythrocytes, malaria parasites
      increase their host cell uptake of diverse solutes including Ca++. The mechanism
      and molecular basis of increased Ca++ permeability remains less well studied than
      that of other solutes. METHODS: Based on an appropriate Ca++ affinity and its
      greater brightness than related fluorophores, Fluo-8 was selected and used to
      develop a robust fluorescence-based assay for Ca++ uptake by human erythrocytes
      infected with Plasmodium falciparum. RESULTS: Both uninfected and infected cells
      exhibited a large Ca++-dependent fluorescence signal after loading with the Fluo
      8 dye. Probenecid, an inhibitor of erythrocyte organic anion transporters,
      abolished the fluorescence signal in uninfected cells; in infected cells, this
      agent increased fluorescence via mechanisms that depend on parasite genotype.
      Kinetic fluorescence measurements in 384-well microplates revealed that the
      infected cell Ca++ uptake is not mediated by the plasmodial surface anion channel
      (PSAC), a parasite nutrient channel at the host membrane; it also appears to be
      distinct from mammalian Ca++ channels. Imaging studies confirmed a low
      intracellular Ca++ in uninfected cells and higher levels in both the host and
      parasite compartments of infected cells. Parasite growth inhibition studies
      revealed a conserved requirement for extracellular Ca++. CONCLUSIONS:
      Nondestructive loading of Fluo-8 into human erythrocytes permits measurement of
      Ca++ uptake kinetics. The greater Ca++ permeability of cells infected with
      malaria parasites is apparent when probenecid is used to inhibit Fluo-8 efflux at
      the host membrane. This permeability is mediated by a distinct pathway and may be
      essential for intracellular parasite development. The miniaturized assay
      presented here should help clarify the precise transport mechanism and may
      identify inhibitors suitable for antimalarial drug development.

PMID- 24885752
TI  - Epistemology of the origin of cancer: a new paradigm.
AB  - BACKGROUND: Carcinogenesis is widely thought to originate from somatic mutations
      and an inhibition of growth suppressors, followed by cell proliferation, tissue
      invasion, and risk of metastasis. Fewer than 10% of all cancers are hereditary;
      the ratio in gastric (1%), colorectal (3-5%) and breast (8%) cancers is even
      less. Cancers caused by infection are thought to constitute some 15% of the non
      hereditary cancers. Those remaining, 70 to 80%, are called "sporadic," because
      they are essentially of unknown etiology. We propose a new paradigm for the
      origin of the majority of cancers. PRESENTATION OF HYPOTHESIS: Our paradigm
      postulates that cancer originates following a sequence of events that include (1)
      a pathogenic stimulus (biological or chemical) followed by (2) chronic
      inflammation, from which develops (3) fibrosis with associated changes in the
      cellular microenvironment. From these changes a (4) pre-cancerous niche develops,
      which triggers the deployment of (5) a chronic stress escape strategy, and when
      this fails to resolve, (6) a transition of a normal cell to a cancer cell occurs.
      If we are correct, this paradigm would suggest that the majority of the findings
      in cancer genetics so far reported are either late events or are epiphenomena
      that occur after the appearance of the pre-cancerous niche. TESTING THE
      HYPOTHESIS: If, based on experimental and clinical findings presented here, this
      hypothesis is plausible, then the majority of findings in the genetics of cancer
      so far reported in the literature are late events or epiphenomena that could have
      occurred after the development of a PCN. Our model would make clear the need to
      establish preventive measures long before a cancer becomes clinically apparent.
      Future research should focus on the intermediate steps of our proposed sequence
      of events, which will enhance our understanding of the nature of carcinogenesis.
      Findings on inflammation and fibrosis would be given their warranted importance,
      with research in anticancer therapies focusing on suppressing the PCN state with
      very early intervention to detect and quantify any subclinical inflammatory
      change and to treat all levels of chronic inflammation and prevent fibrotic
      changes, and so avoid the transition from a normal cell to a cancer cell.
      IMPLICATION OF THE HYPOTHESIS: The paradigm proposed here, if proven, spells out
      a sequence of steps, one or more of which could be interdicted or modulated early
      in carcinogenesis to prevent or, at a minimum, slow down the progression of many
      cancers.

PMID- 24885756
TI  - Melanin-templated rapid synthesis of silver nanostructures.
AB  - BACKGROUND: As a potent antimicrobial agent, silver nanostructures have been used
      in nanosensors and nanomaterial-based assays for the detection of food relevant
      analytes such as organic molecules, aroma, chemical contaminants, gases and food
      borne pathogens. In addition silver based nanocomposites act as an antimicrobial
      for food packaging materials. In this prospective, the food grade melanin pigment
      extracted from sponge associated actinobacterium Nocardiopsis alba MSA10 and
      melanin mediated synthesis of silver nanostructures were studied. Based on the
      present findings, antimicrobial nanostructures can be developed against food
      pathogens for food industrial applications. RESULTS: Briefly, the sponge
      associated actinobacterium N. alba MSA10 was screened and fermentation conditions
      were optimized for the production of melanin pigment. The Plackett-Burman design
      followed by a Box-Behnken design was developed to optimize the concentration of
      most significant factors for improved melanin yield. The antioxidant potential,
      reductive capabilities and physiochemical properties of Nocardiopsis melanin was
      characterized. The optimum production of melanin was attained with pH 7.5,
      temperature 35 degrees C, salinity 2.5%, sucrose 25 g/L and tyrosine 12.5 g/L
      under submerged fermentation conditions. A highest melanin production of 3.4
      mg/ml was reached with the optimization using Box-Behnken design. The purified
      melanin showed rapid reduction and stabilization of silver nanostructures. The
      melanin mediated process produced uniform and stable silver nanostructures with
      broad spectrum antimicrobial activity against food pathogens. CONCLUSIONS: The
      melanin pigment produced by N. alba MSA10 can be used for environmentally benign
      synthesis of silver nanostructures and can be useful for food packaging
      materials. The characteristics of broad spectrum of activity against food
      pathogens of silver nanostructures gives an insight for their potential
      applicability in incorporation of food packaging materials and antimicrobials for
      stored fruits and foods.

PMID- 24885755
TI  - Excellent local control with IOERT and postoperative EBRT in high grade extremity
      sarcoma: results from a subgroup analysis of a prospective trial.
AB  - BACKGROUND: To report the results of a subgroup analysis of a prospective phase
      II trial focussing on radiation therapy and outcome in patients with extremity
      soft tissue sarcomas (STS). METHODS: Between 2005 and 2010, 50 patients (pts)
      with high risk STS (size >= 5 cm, deep/extracompartimental location, grade II-III
      (FNCLCC)) were enrolled. The protocol comprised 4 cycles of neoadjuvant
      chemotherapy with EIA (etoposide, ifosfamide and doxorubicin), definitive surgery
      with IOERT, postoperative EBRT and 4 adjuvant cycles of EIA. 34 pts, who suffered
      from extremity tumors and received radiation therapy after limb-sparing surgery,
      formed the basis of this subgroup analysis. RESULTS: Median follow-up from
      inclusion was 48 months in survivors. Margin status was R0 in 30 pts (88%) and R1
      in 4 pts (12%). IOERT was performed as planned in 31 pts (91%) with a median dose
      of 15 Gy, a median electron energy of 6 MeV and a median cone size of 9 cm. All
      patients received postoperative EBRT with a median dose of 46 Gy after IOERT or
      60 Gy without IOERT. Median time from surgery to EBRT and median EBRT duration
      was 36 days, respectively. One patient developed a local recurrence while 11
      patients showed nodal or distant failures. The estimated 5-year rates of local
      control, distant control and overall survival were 97%, 66% and 79%,
      respectively. Postoperative wound complications were found in 7 pts (20%),
      resulting in delayed EBRT (>60 day interval) in 3 pts. Acute radiation toxicity
      mainly consisted of radiation dermatitis (grade II: 24%, no grade III reactions).
      4 pts developed grade I/II radiation recall dermatitis during adjuvant
      chemotherapy, which resolved during the following cycles. Severe late toxicity
      was observed in 6 pts (18%). Long-term limb preservation was achieved in 32 pts
      (94%) with good functional outcome in 81%. CONCLUSION: Multimodal therapy
      including IOERT and postoperative EBRT resulted in excellent local control and
      good overall survival in patients with high risk STS of the extremities with
      acceptable acute and late radiation side effects. Limb preservation with good
      functional outcome was achieved in the majority of patients. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01382030, EudraCT 2004-002501-72, 17.06.2011.

PMID- 24885757
TI  - A case of multiple hepatic angiomyolipomas with high (18) F-fluorodeoxyglucose
      uptake.
AB  - BACKGROUND: Hepatic angiomyolipoma is a rare benign mesenchymal tumor. We report
      an unusual case of a patient with multiple hepatic angiomyolipomas exhibiting
      high (18) F-fluorodeoxyglucose (FDG) uptake. CASE PRESENTATION: A 29-year-old man
      with a medical history of tuberous sclerosis was admitted to our hospital for
      fever, vomiting, and weight loss. Abdominal dynamic computed tomography revealed
      faint hypervascular hepatic tumors in segments 5 (67 mm) and 6 (10 mm), with
      rapid washout and clear borders; however, the tumors exhibited no definite fatty
      density. Abdominal magnetic resonance imaging revealed that the hepatic lesions
      were slightly hypointense on T1-weighted imaging, slightly hyperintense on T2
      weighted imaging, and hyperintense with no apparent fat component on diffusion
      weighted imaging. FDG-positron emission tomography (PET) imaging revealed high
      maximum standardized uptake values (SUVmax) of 6.27 (Segment 5) and 3.22 (Segment
      6) in the hepatic tumors. A right hepatic lobectomy was performed, and part of
      the middle hepatic vein was also excised. Histological examination revealed that
      these tumors were characterized by the background infiltration of numerous
      inflammatory cells, including spindle-shaped cells, and a resemblance to an
      inflammatory pseudotumor. Immunohistochemical evaluation revealed that the tumor
      stained positively for human melanoma black-45. The tumor was therefore
      considered an inflammatory pseudotumor-like angiomyolipoma. Although several case
      reports of hepatic angiomyolipoma have been described or reviewed in the
      literature, only 3 have exhibited high (18) F-FDG uptake on PET imaging with
      SUVmax ranging from 3.3-4.0. In this case, increased (18) F-FDG uptake is more
      likely to appear, particularly if the inflammation is predominant. CONCLUSION:
      Although literature regarding the role of (18) F-FDG-PET in hepatic
      angiomyolipoma diagnosis is limited and the diagnostic value of (18) F-FDG-PET
      has not yet been clearly defined, the possibility that hepatic angiomyolipoma
      might exhibit high (18) F-FDG uptake should be considered.

PMID- 24885759
TI  - Spectral domain optical coherence tomography in patients after successful
      management of postoperative endophthalmitis following cataract surgery by pars
      plana vitrectomy.
AB  - BACKGROUND: Acute severe postoperative endophthalmitis may lead to severe vision
      loss. The aim of this study was the analysis of macular microstructure imaged by
      spectral domain optical coherence tomography in patients after pars plana
      vitrectomy due to postcataract endophthalmitis. METHODS: A cross sectional study
      was carried out in 17 patients who had cataract surgery in both eyes and
      underwent unilateral pars plana vitrectomy due to postcataract endophthalmitis.
      Postoperative best corrected visual acuity was determined in both eyes.
      Evaluation of macular thickness, macular volume, peripapillary retinal nerve
      fiber layer thickness and choroidal thickness using enhanced depth imaging
      technique was performed by spectral domain optical coherence tomography. The
      measurements obtained in the operated eye were compared to the fellow eye by
      Wilcoxon matched pair test. Correlation test was performed by Spearman rank
      order. RESULTS: A mean postoperative best corrected visual acuity of 63 +/- 30
      ETDRS letters versus 75 +/- 21 letters was achieved in the study and fellow eyes,
      respectively, after a mean of 5.3 +/- 4.5 months (p = 0.1). The mean macular
      thickness was 320.6 +/- 28.8 MUm SD in the study eyes compared to 318.4 +/- 18.8
      MUm in the fellow eyes (p = 0.767). No differences were noted in macular volume
      (p = 0.97) and in peripapillary retinal nerve fiber layer thickness (p = 0.31).
      Choroidal thickness was significantly lower in the study eyes compared to the
      fellow eyes (p = 0.018). Epiretinal membrane was found in 7 eyes after
      endophthalmitis, while in the fellow eyes only in 3 cases (p = 0.13, Fisher's
      exact test). CONCLUSION: Choroidal thickness decreased significantly after
      endophthalmitis, but there was no functional correlation with the changes in
      choroidal microstructure. The development of epiretinal membranes may be
      associated with either vitrectomy or endophthalmitis in the history. Absence of
      other significant structural and morphological findings shows that successful
      treatment may guarantee good clinical results even in long term after this severe
      postoperative complication.

PMID- 24885758
TI  - Using technology to deliver cancer follow-up: a systematic review.
AB  - BACKGROUND: People with cancer receive regular structured follow up after initial
      treatment, usually by a specialist in a cancer centre. Increasing numbers of
      cancer survivors prompts interest in alternative structured follow-up models.
      There is worldwide evidence of increasing interest in delivering cancer follow-up
      using technology. This review sough evidence supporting the use of technology in
      cancer follow-up from good quality randomised controlled trials. METHOD: A search
      strategy was developed to identify randomised controlled trials and reviews of
      randomised trials of interventions delivering some aspect of structured cancer
      follow-up using new technologies. Databases searched were: All EBM Reviews;
      Embase; Medline (No Revisions); Medline (Non-Indexed Citations), and CAB
      Abstracts. Included articles were published in English between 2000 and 2014. Key
      words were generated by the research question. Papers were read independently and
      appraised using a standardised checklist by two researchers, with differences
      being resolved by consensus [J Epidemiol Community Health, 52:377-384, 1998].
      Information was collected on the purpose, process, results and limitations of
      each study. All outcomes were considered, but particular attention paid to areas
      under consideration in the review question. RESULTS: The search strategy
      generated 22879 titles. Following removal of duplicates and abstract review 17
      full papers pertaining to 13 randomised controlled studies were reviewed. Studies
      varied in technologies used and the elements of follow-up delivered, length of
      follow-up, tumour type and numbers participating. Most studies employed only
      standard telephone follow-up. Most studies involved women with breast cancer and
      included telephone follow-up. Together the results suggest that interventions
      comprising technology had not compromised patient satisfaction or safety, as
      measured by symptoms, health related quality of life or psychological distress.
      There was insufficient evidence to comment on the cost effectiveness of
      technological cancer follow-up interventions. CONCLUSIONS: Modern technology
      could deliver cancer follow-up that is acceptable and safe. More research is
      required to develop cancer follow-up systems which exploit modern technology,
      which should be assessed using randomised trials, with consistent outcomes, so
      that evidence on the acceptability, safety, cost effectiveness and impact in
      quality of life of technological follow-up can accumulate and be made available
      to patients, professionals and policy makers.

PMID- 24885760
TI  - Local understandings of care during delivery and postnatal period to inform home
      based package of newborn care interventions in rural Ethiopia: a qualitative
      study.
AB  - BACKGROUND: Despite a substantial decrease in child mortality in Ethiopia over
      the past decade, neonatal mortality remains unchanged (37/1000 live-births). This
      paper describes a qualitative study on beliefs and practices on immediate newborn
      and postnatal care in four rural communities of Ethiopia conducted to inform
      development of a package of community-based interventions targeting newborns.
      METHODS: The study team conducted eight key informant interviews (KII) with
      grandmothers, 27 in-depth interviews (IDI) with mothers; seven IDI with
      traditional birth attendants (TBA) and 15IDI with fathers, from four purposively
      selected communities located in Sidama Zone of Southern Nationalities, Nations,
      and Peoples (SNNP) Region and in East Shewa and West Arsi Zones of Oromia Region.
      RESULTS: In the study communities deliveries occurred at home. After cutting the
      umbilical cord, the baby is put to the side of the mother, not uncommonly with no
      cloth covering. This is largely due to attendants focusing on delivery of the
      placenta which is reinforced by the belief that the placenta is the 'house' or
      'blanket' of the baby and that any "harm" caused to the placenta will transfer to
      the newborn. Applying butter or ointment to the cord "to speed drying" is common
      practice. Initiation of breastfeeding is often delayed and women commonly report
      discarding colostrum before initiating breastfeeding. Sub-optimal breastfeeding
      practices continue, due to perceived inadequate maternal nutrition and breast
      milk often leading to the provision of herbal drinks. Poor thermal care is also
      demonstrated through lack of continued skin-to-skin contact, exposure of newborns
      to smoke, frequent bathing-often with cold water baths for low-birth weight or
      small babies; and, poor hygienic practices are reported, particularly hand
      washing prior to contact with the newborn. CONCLUSION: Cultural beliefs and
      newborn care practices do not conform to recommended standards. Local
      perspectives related to newborn care practices should inform behaviour change
      messages. Such messages should target mothers, grandmothers, TBAs, other female
      family members and fathers.

PMID- 24885761
TI  - One-step synthesis of nitrogen-containing medium-sized rings via alpha-imino
      diazo intermediates.
AB  - Eight- and 9-membered dioxazocines and dioxazonines are readily synthesized
      starting from N-sulfonyl-1,2,3-triazoles in a single-step procedure. A perfect
      regioselectivity and generally good yields (up to 92%) are obtained under
      dirhodium catalysis using 1,3-dioxolane and 1,3-dioxane as solvents and reagents.

PMID- 24885762
TI  - Electromyographic analysis of masseter muscle in newborns during suction in
      breast, bottle or cup feeding.
AB  - BACKGROUND: When breastfeeding is difficult or impossible during the neonatal
      period, an analysis of muscle activity can help determine the best method for
      substituting it to promote the child's development. The aim of this study was to
      analyze the electrical activity of the masseter muscle using surface
      electromyography during suction in term newborns by comparing breastfeeding,
      bottle and cup feeding. METHODS: An observational, cross-sectional analytical
      study was carried out on healthy, clinically stable term infants, assigned to
      receive either breast, or bottle or cup feeding. Setting was a Baby Friendly
      accredited hospital. Muscle activity was analyzed when each infant showed
      interest in sucking using surface electromyography. Root mean square averages
      (RMS) recorded in microvolts were transformed into percentages (normalization) of
      the reference value. The three groups were compared by ANOVA; the "stepwise"
      method of the multiple linear regression analysis tested the model which best
      defined the activity of the masseter muscle in the sample at a significance level
      of 5%. RESULTS: Participants were 81 full term newborns (27 per group), from 2 to
      28 days of life. RMS values were lower for bottle (mean 44.2%, SD 14.1) than
      breast feeding (mean 58.3%, SD 12.7) (P = 0.003, ANOVA); cup feeding (52.5%, SD
      18.2%) was not significantly different (P > 0.05). For every gram of weight
      increase, RMS increased by 0.010 units. CONCLUSIONS: Masseter activity was
      significantly higher in breastfed newborns than in bottle-fed newborns, who
      presented the lowest RMS values. Levels of masseter activity during cup-feeding
      were between those of breast and bottle feeding, and did not significantly differ
      from either group. This study in healthy full term neonates endorses cup rather
      than bottle feeding as a temporary substitute for breastfeeding.

PMID- 24885763
TI  - VMP1-deficient Chlamydomonas exhibits severely aberrant cell morphology and
      disrupted cytokinesis.
AB  - BACKGROUND: The versatile Vacuole Membrane Protein 1 (VMP1) has been previously
      investigated in six species. It has been shown to be essential in macroautophagy,
      where it takes part in autophagy initiation. In addition, VMP1 has been
      implicated in organellar biogenesis; endo-, exo- and phagocytosis, and protein
      secretion; apoptosis; and cell adhesion. These roles underly its proven
      involvement in pancreatitis, diabetes and cancer in humans. RESULTS: In this
      study we analyzed a VMP1 homologue from the green alga Chlamydomonas reinhardtii.
      CrVMP1 knockdown lines showed severe phenotypes, mainly affecting cell division
      as well as the morphology of cells and organelles. We also provide several pieces
      of evidence for its involvement in macroautophagy. CONCLUSION: Our study adds a
      novel role to VMP1's repertoire, namely the regulation of cytokinesis. Though the
      directness of the observed effects and the mechanisms underlying them remain to
      be defined, the protein's involvement in macroautophagy in Chlamydomonas, as
      found by us, suggests that CrVMP1 shares molecular characteristics with its
      animal and protist counterparts.

PMID- 24885764
TI  - Center of pressure displacements during gait initiation in individuals with
      obesity.
AB  - BACKGROUND: Obesity is known to affect balance and gait pattern increasing the
      risk of fall and injury as compared to the lean population. Such risk is
      particularly high during postural transitions. Gait initiation (GI) is a
      transient procedure between static upright posture and steady-state locomotion,
      which includes anticipatory antero-posterior and lateral movements. GI requires
      propulsion and balance control. The aim of this study was to characterise
      quantitatively the strategy of obese subjects during GI using parameters obtained
      by the Center of Pressure (CoP) track. METHODS: 20 obese individuals and 15 age
      matched healthy subjects were tested using a force platform during the initiation
      trials. CoP plots were divided in different phases, which identified the
      anticipatory postural adjustments (APA1, APA2) and a movement phase (LOC).
      Duration, length and velocity of the CoP trace in these phases were calculated
      and compared. RESULTS AND DISCUSSION: The results show that the main
      characteristic of GI in obese participants is represented by a higher excursion
      in medio-lateral direction. This condition lead to longer APA length and
      duration, which are statistical significant during APA2 when compared to control
      subjects. We also found longer duration of APA1 and LOC phases. In terms of
      velocity, most of the phases were characterised by a reduced CoP velocity in
      antero-posterior direction and faster movement in medio-lateral direction as
      compared to the control group. CONCLUSIONS: Our findings provide novel evidence
      in GI in obese subjects that may serve for developing exercise programs aimed at
      specifically improving balance in both the antero-posterior and lateral
      directions. Such programs together with weight management may be beneficial for
      improving stability during postural transitions and reducing risk of fall in this
      population.

PMID- 24885765
TI  - The association of mavenism and pleasure with food involvement in older adults.
AB  - BACKGROUND: Food involvement is concerned with the involvement people have in the
      preparation and consumption of food. Little is known about older people's food
      involvement or about the factors which may influence it. Therefore the main aim
      of this study was to examine food involvement and its associations among older
      Australians. METHODS: An Internet-based nationwide survey of 1,041 people aged 55
      years and over (M = 66 years, SD 6.99) was conducted in 2012. Quota sampling was
      used to ensure that the age, gender and state of residence of the respondents
      were representative of the Australian population aged over 55 years. Bell and
      Marshall's Food Involvement Scale was administered, along with questions
      pertaining to socio-demographic, social and hedonic factors. RESULTS: Overall
      predictor variables explained 45% (p = <0.0001) of variance in food involvement.
      Food mavenism and pleasure motivation for food were the factors most strongly
      associated with food involvement (beta = .36; 95% CI .46, .61; p = < 0.0001 and
      beta = .31; 95% CI .78, 1.08; p = < 0.0001, respectively). The predictive ability
      of demographic factors was reasonably poor. CONCLUSIONS: Food mavenism and
      pleasure motivation are stronger predictors of Food Involvement than demographic
      factors. This suggests communication and health promotion opportunities among
      older people.

PMID- 24885767
TI  - Enhancing medicine price transparency through price information mechanisms.
AB  - BACKGROUND: Medicine price information mechanisms provide an essential tool to
      countries that seek a better understanding of product availability, market prices
      and price compositions of individual medicines. To be effective and contribute to
      cost savings, these mechanisms need to consider prices in their particular
      contexts when comparing between countries. This article discusses in what ways
      medicine price information mechanisms can contribute to increased price
      transparency and how this may affect access to medicines for developing
      countries. METHODS: We used data collected during the course of a WHO project
      focusing on the development of a vaccine price and procurement information
      mechanism. The project collected information from six medicine price information
      mechanisms and interviewed data managers and technical experts on key aspects as
      well as observed market effects of these mechanisms.The reviewed mechanisms were
      broken down into categories including objective and target audience, as well as
      the sources, types and volumes of data included. Information provided by the
      mechanisms was reviewed according to data available on medicine prices, product
      characteristics, and procurement modalities. RESULTS: We found indications of
      positive effects on access to medicines resulting from the utilization of the
      reviewed mechanisms. These include the uptake of higher quality medicines, more
      favorable results from contract negotiations, changes in national pricing
      policies, and the decrease of prices in certain segments for countries
      participating in or deriving data from the various mechanisms. CONCLUSION: The
      reviewed mechanisms avoid the methodological challenges observed for medicine
      price comparisons that only use national price databases. They work with high
      quality data and display prices in the appropriate context of procurement
      modalities as well as the peculiarities of purchasing countries. Medicine price
      information mechanisms respond to the need for increased medicine price
      transparency and have the potential to contribute to improved access to medicines
      in developing countries.Additional research is required to explore more specific
      aspects. These include the market effects of dedicated donor funds for certain
      medicines to explain the driving force of user demands, and the effects of
      increased price transparency on different groups of medicines in context of the
      maturity of their markets.

PMID- 24885766
TI  - Radiotherapy in patients with distant metastatic breast cancer.
AB  - BACKGROUND: The study evaluates frequency of and indications for disease-related
      radiotherapy in the palliative breast cancer (BC) situation and analyzes in which
      phase of the palliative disease course radiotherapy was applied. PATIENTS &
      METHODS: 340 patients who developed distant metastatic disease (DMD) and died
      (i.e. patients with completed disease courses) were analyzed. RESULTS: 165
      patients (48.5%) received palliative radiotherapy (255 series, 337 planning
      target volumes) as a part of palliative care. The most common sites for
      radiotherapy were the bone (217 volumes, 64.4% of all radiated volumes) and the
      brain (57 volumes, 16.9%). 127 series (49.8%) were performed in the first third
      of the metastatic disease survival (MDS) period; 84 series (32.8%) were performed
      in the last third. The median survival after radiotherapy was 10 months. Patients
      who had received radiation were younger compared to those who had no radiation
      (61 vs. 68 years, p < 0.001) and had an improved MDS (26 vs. 14 months, p <
      0.001). Compared to rapidly progressive disease courses with short survival
      times, in cases where effective systemic therapy achieved a longer MDS (>=24
      months), radiotherapy was significantly more often a part of the multimodal
      palliative therapy (52.1% vs. 37.1%, p = 0.006). CONCLUSIONS: In a cohort of BC
      patients with DMD, nearly one half of the patients received radiotherapy during
      the palliative disease course. In a palliative therapy approach, which
      increasingly allows for treatment according to the principles of a chronic
      disease, radiotherapy has a clearly established role in the therapy concept.

PMID- 24885768
TI  - Reconstitution of internal target volumes by combining four-dimensional computed
      tomography and a modified slow computed tomography scan in stereotactic body
      radiotherapy planning for lung cancer.
AB  - BACKGROUND: To evaluate the volumetric and geometric differences in the ITVs
      generated by four-dimensional (4D) computed tomography (CT), a modified slow CT
      scan, and a combination of these CT methods in lung cancer patients treated with
      stereotactic body radiotherapy (SBRT). METHODS: Both 4D CT and modified slow CT
      using a multi-slice CT scanner were performed for SBRT planning in 14 patients
      with 15 pulmonary targets. Volumetric and geometric analyses were performed for
      (1) ITVall, generated by combining the gross tumor volumes (GTVs) from all 8
      phases of the 4D CT; (2) ITV2, generated by combining the GTVs from 2 extreme
      phases of the 4D CT; (3) ITVslow, derived from the GTV on the modified slow CT
      scan; (4) ITVall+slow, generated by combining ITVall and ITVslow; and (5)
      ITV2+slow, generated by combining ITV2 and ITVslow. Three SBRT plans were
      performed using 3 ITVs to assess the dosimetric effects on normal lung caused by
      the various target volumes. RESULTS: ITVall (11.8 +/- 8.3 cm3) was significantly
      smaller than ITVall+slow (12.5 +/- 8.9 cm3), with mean values of 5.8% for the
      percentage volume difference, and a mean of 7.5% of ITVslow was not encompassed
      in ITVall. The geometric coverages of ITV2 and ITVslow for ITVall were 84.7 +/-
      6.6% and 76.2 +/- 9.3%, respectively, but the coverage for ITVall increased to
      90.9 +/- 5.9% by using the composite of these two ITVs. There were statistically
      significant increases in the lung-dose parameters of the plans based on
      ITVall+slow compared to the plans based on ITVall or ITV2+slow. However, the
      magnitudes of these differences were relatively small, with a value of less than
      3% in all dosimetric parameters. CONCLUSIONS: Due to its ability to provides
      additional motion information, the combination of 4D CT and a modified slow CT
      scan in SBRT planning for lung cancer can be used to reduce possible errors in
      true target delineation caused by breathing pattern variations.

PMID- 24885769
TI  - GAP-Seq: a method for identification of DNA palindromes.
AB  - BACKGROUND: Closely spaced long inverted repeats, also known as DNA palindromes,
      can undergo intrastrand annealing to form DNA hairpins. The ability to form these
      hairpins results in genome instability, difficulties in maintaining clones in
      Escherichia coli and major problems for most DNA sequencing approaches. Because
      of their role in genomic instability and gene amplification in some human
      cancers, it is important to develop systematic approaches to detect and
      characterize DNA palindromes. RESULTS: We developed a new protocol to identify
      palindromes that couples the S1 nuclease treated Cot0 DNA (GAPF) with high
      throughput sequencing (GAP-Seq). Unlike earlier protocols, it does not involve
      restriction enzymatic digestion prior to DNA snap-back thereby preserving longer
      DNA sequences. It also indicates the location of the novel junction, which can
      then be recovered. Using MCF-7 breast cancer cell line as the proof-of-principle
      analysis, we have identified 35 palindrome candidates and physically
      characterized the top 5 candidates and their junctions. Because this protocol
      eliminates many of the false positives that plague earlier techniques, we have
      improved palindrome identification. CONCLUSIONS: The GAP-Seq approach underscores
      the importance of developing new tools for identifying and characterizing
      palindromes, and provides a new strategy to systematically assess palindromes in
      genomes. It will be useful for studying human cancers and other diseases
      associated with palindromes.

PMID- 24885770
TI  - Spontaneous regression of metastatic cancer cells in the lymph node: a case
      report.
AB  - BACKGROUND: Spontaneous regression of a malignant tumor is the phenomenon of
      disappearance of cancer cells without any treatments and it can be induced by an
      enhanced tumor-targeting immune response. However, there has not been a
      comprehensive immunological overview to compare the tumor-regressed lymph nodes
      and metastatic lymph nodes in the same patient. CASE PRESENTATION: We conducted a
      histologic analysis of various immune cells in an Asian female patient with
      buccal cancer (squamous cell carcinomas), in which the spontaneous regression of
      metastatic lymphadenopathy was confirmed by surgical pathology. The immune cell
      profiles between the metastatic nodes and the tumor-regressed nodes were
      compared. Tumor regression was confirmed by hematoxylin & eosin and
      cytokeratin/Ki-67 staining. Distinct differences were observed in Foxp3(+)
      regulatory T (Treg) cells and CD56(+) natural killer (NK) cells; a higher density
      of Foxp3(+) Treg cells was found in metastatic lymph nodes and more infiltration
      of CD56(+) NK cells in tumor regressed lymph nodes. Other immune cell populations
      (CD4, CD8, CD20, CD68, CD86, CD123, CD11c, and mannose receptor) showed no
      discernible differences in marker expression in the nodes examined. CONCLUSION:
      Less recruitment of Treg and high infiltration of NK cells were key features in
      tumor-regressed lymph nodes. Modulation of Treg or NK cells may be a good
      therapeutic method to control lymph node metastasis.

PMID- 24885772
TI  - Substituent effects on rates and torquoselectivities of electrocyclic ring
      openings of N-substituted 2-azetines.
AB  - Transition structures for the conrotatory electrocyclic ring-opening reactions of
      N-substituted 2-azetines were computed with the density functional M06-2X/6
      31+G(d,p). A wide range of substituents from pi acceptors (e.g., CHO, CN) to pi
      donors (NMe2, OMe) was explored. Acceptor substituents delocalize the nitrogen
      lone pair and stabilize the reactant state of 2-azetines, while donors
      destabilize the 2-azetine reactant state. The conrotatory ring-opening is
      torquoselective, and the transition state for the outward rotation of the N
      substituent and inward rotation of the nitrogen lone pair is preferred. This
      transition structure is stabilized by an interaction between the nitrogen lone
      pair and the vacant pi* orbital. The activation free energies are linearly
      related to the reaction free energies and the Taft sigmaR(0) parameter. 

PMID- 24885771
TI  - Role of metal oxide nanoparticles in histopathological changes observed in the
      lung of welders.
AB  - BACKGROUND: Although major concerns exist regarding the potential consequences of
      human exposure to nanoparticles (NP), no human toxicological data is currently
      available. To address this issue, we took welders, who present various adverse
      respiratory outcomes, as a model population of occupational exposure to NP.The
      aim of this study was to evaluate if welding fume-issued NP could be responsible,
      at least partially, in the lung alterations observed in welders. METHODS: A
      combination of imaging and material science techniques including ((scanning)
      transmission electron microscopy ((S)TEM), energy dispersive X-ray (EDX), and X
      ray microfluorescence (MUXRF)), was used to characterize NP content in lung
      tissue from 21 welders and 21 matched control patients. Representative NP were
      synthesized, and their effects on macrophage inflammatory secretome and migration
      were evaluated, together with the effect of this macrophage inflammatory
      secretome on human lung primary fibroblasts differentiation. RESULTS: Welding
      related NP (Fe, Mn, Cr oxides essentially) were identified in lung tissue
      sections from welders, in macrophages present in the alveolar lumen and in
      fibrous regions. In vitro macrophage exposure to representative NP (Fe2O3, Fe3O4,
      MnFe2O4 and CrOOH) induced the production of a pro-inflammatory secretome
      (increased production of CXCL-8, IL-1beta, TNF-alpha, CCL-2, -3, -4, and to a
      lesser extent IL-6, CCL-7 and -22), and all but Fe3O4 NP induce an increased
      migration of macrophages (Boyden chamber). There was no effect of NP-exposed
      macrophage secretome on human primary lung fibroblasts differentiation.
      CONCLUSIONS: Altogether, the data reported here strongly suggest that welding
      related NP could be responsible, at least in part, for the pulmonary inflammation
      observed in welders. These results provide therefore the first evidence of a link
      between human exposure to NP and long-term pulmonary effects.

PMID- 24885773
TI  - Outcomes following large joint arthroplasty: does socio-economic status matter?
AB  - BACKGROUND: We sought to determine whether socio-economic status (SES) is an
      independent predictor of outcome following total knee (TKR) and hip (THR)
      replacement in Australians. METHODS: In this prospective cohort study, we
      included patients undergoing TKR and THR in a public hospital in whom baseline
      and 12-month follow-up data were available. SES was determined using the
      Australian Bureau of Statistics 'Index of Relative Advantage and Disadvantage'.
      Other independent variables included patients' demographics, comorbidities and
      procedure-related variables. Outcome measures were the International Knee Society
      Score and Harris Hip Score pain and function subscales, and the Short Form Health
      Survey (SF-12) physical and mental component scores. RESULTS: Among 1,016
      patients undergoing TKR and 835 patients undergoing THR, in multiple regression
      analysis, SES score was not independently associated with pain and functional
      outcomes. Female sex, older age, being a non-English speaker, higher body mass
      index and presence of comorbidities were associated with greater post-operative
      pain and poorer functional outcomes following arthroplasty. Better baseline
      function, physical and mental health, and lower baseline level of pain were
      associated with better outcomes at 12 months. In univariate analysis, for TKR,
      the improvement in SF-12 mental health score post arthroplasty was greater in
      patients of lower SES (3.8 +/- 12.9 versus 1.5 +/- 12.2, p=0.008), with a
      statistically significant inverse association between SES score and post
      operative SF-12 mental health score in linear regression analysis (coefficient
      0.28, 95% CI: -0.52 to -0.04, p=0.02). CONCLUSIONS: When adjustments are made for
      other covariates, SES is not an independent predictor of pain and functional
      outcome following large joint arthroplasty in Australian patients. However,
      relative to baseline, patients in lower socioeconomic groups are likely to have
      greater mental health benefits with TKR than more privileged patients. Large
      joint arthroplasty should be made accessible to patients of all SES.

PMID- 24885774
TI  - Study of Coxsackie B viruses interactions with Coxsackie Adenovirus receptor and
      Decay-Accelerating Factor using Human CaCo-2 cell line.
AB  - BACKGROUND: Decay Accelerating Factor (DAF) and Coxsackievirus-Adenovirus
      Receptor (CAR) have been identified as cellular receptors for Coxsackie B viruses
      (CV-B). The aim of this study is to elucidate the different binding properties of
      CV-B serotypes and to find out if there are any amino acid changes that could be
      associated to the different phenotypes.Twenty clinical CV-B isolates were tested
      on CaCo-2 cell line using anti-DAF (BRIC216) and anti-CAR (RmcB) antibodies. CV
      B3 Nancy prototype strain and a recombinant strain (Rec, CV-B3/B4) were tested in
      parallel. The P1 genomic region of 12 CV-B isolates from different serotypes was
      sequenced and the Trans-Epithelial Electrical Resistance (TEER) along with the
      virus growth cycle was measured. RESULTS: Infectivity assays revealed clear
      differences between CV-B isolates with regard to their interactions with DAF and
      CAR. All tested CV-B isolates showed an absolute requirement for CAR but varied
      in their binding to DAF. We also reported that for some isolates of CV-B, DAF
      attachment was not adapted. Genetic analysis of the P1 region detected multiple
      differences in the deduced amino acid sequences. CONCLUSION: Within a given
      serotype, variations exist in the capacity of virus isolates to bind to specific
      receptors, and variants with different additional ligands may arise during
      infection in humans as well as in tissue culture.

PMID- 24885775
TI  - Characterizing semen parameters and their association with reactive oxygen
      species in infertile men.
AB  - BACKGROUND: A routine semen analysis is a first step in the laboratory evaluation
      of the infertile male. In addition, other tests such as measurement of reactive
      oxygen species can provide additional information regarding the etiology of male
      infertility. The objective of this study was to investigate the association of
      semen parameters with reactive oxygen species (ROS) in two groups: healthy donors
      of unproven and proven fertility and infertile men. In addition, we sought to
      establish an ROS cutoff value in seminal plasma at which a patient may be
      predicted to be infertile. METHODS: Seminal ejaculates from 318 infertile
      patients and 56 donors, including those with proven fertility were examined for
      semen parameters and ROS levels. Correlations were determined between traditional
      semen parameters and levels of ROS among the study participants. ROS levels were
      measured using chemiluminescence assay. Receiver operating characteristic curves
      were obtained to calculate a cutoff value for these tests. RESULTS: Proven Donors
      (n = 28) and Proven Donors within the past 2 years (n = 16) showed significantly
      better semen parameters than All Patients group (n = 318). Significantly lower
      ROS levels were seen in the two Proven Donor groups compared with All Patients.
      The cutoff value of ROS in Proven Donors was determined to be 91.9 RLU/s with a
      specificity of 68.8% and a sensitivity of 93.8%. CONCLUSIONS: Infertile men,
      irrespective of their clinical diagnoses, have reduced semen parameters and
      elevated ROS levels compared to proven fertile men who have established a
      pregnancy recently or in the past. Reactive oxygen species are negatively
      correlated with traditional semen parameters such as concentration, motility and
      morphology. Measuring ROS levels in the seminal ejaculates provides clinically
      relevant information to clinicians.

PMID- 24885776
TI  - Inhibition of hepatitis C virus by an M1GS ribozyme derived from the catalytic
      RNA subunit of Escherichia coli RNase P.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a human pathogen causing chronic liver
      disease in about 200 million people worldwide. However, HCV resistance to
      interferon treatment is one of the important clinical implications, suggesting
      the necessity to seek new therapies. It has already been shown that some forms of
      the catalytic RNA moiety from E. coli RNase P, M1 RNA, can be introduced into the
      cytoplasm of mammalian cells for the purpose of carrying out targeted cleavage of
      mRNA molecules. Our study is to use an engineering M1 RNA (i.e. M1GS) for
      inhibiting HCV replication and demonstrates the utility of this ribozyme for
      antiviral applications. RESULTS: By analyzing the sequence and structure of the
      5' untranslated region of HCV RNA, a putative cleavage site (C67-G68) was
      selected for ribozyme designing. Based on the flanking sequence of this site, a
      targeting M1GS ribozyme (M1GS-HCV/C67) was constructed by linking a custom guide
      sequence (GS) to the 3' termini of catalytic RNA subunit (M1 RNA) of RNase P from
      Escherichia coli through an 88 nt-long bridge sequence. In vitro cleavage assays
      confirmed that the engineered M1GS ribozyme cleaved the targeted RNA
      specifically. Moreover, ~85% reduction in the expression levels of HCV proteins
      and >1000-fold reduction in viral growth were observed in supernatant of cultured
      cells that transfected the functional ribozyme. In contrast, the HCV core
      expression and viral growth were not significantly affected by a "disabled"
      ribozyme (i.e. M1GS-HCV/C67*). Moreover, cholesterol-conjugated M1GS ribozyme
      (i.e. Chol-M1GS-HCV/C67) showed almost the same bioactivities with M1GS-HCV/C67,
      demonstrating the potential to improve in vivo pharmacokinetic properties of M1GS
      based RNA therapeutics. CONCLUSION: Our results provide direct evidence that the
      M1GS ribozyme can function as an antiviral agent and effectively inhibit gene
      expression and multiplication of HCV.

PMID- 24885778
TI  - Do community-based strategies reduce HIV risk among people who inject drugs in
      China? A quasi-experimental study in Yunnan and Guangxi provinces.
AB  - BACKGROUND: HIV transmission among people who inject drugs (PWID) is high in
      Yunnan and Guangxi provinces in southwest China. To address this epidemic,
      Population Services International (PSI) and four cooperating agencies implemented
      a comprehensive harm reduction model delivered through community-based drop
      incenters (DiC) and peer-led outreach to reduce HIV risk among PWID. METHODS: We
      used 2012 behavioral survey data to evaluate the effectiveness of this model for
      achieving changes in HIV risk, including never sharing needles or syringes,
      always keeping a clean needle on hand, HIV testing and counseling (HTC), and
      consistent condom use. We used respondent-driven sampling to recruit respondents.
      We then used coarsened exact matching (CEM) to match respondents during analysis
      to improve estimation of the effects of exposure to both DiC and outreach, only
      DiC, and only outreach, modeled using multivariable logistic regression. RESULTS:
      We found a significant relationship between participating in both peer-led DiC
      based activities and outreach and having a new needle on hand (odds ratio (OR)
      1.53, p < .05) and consistent condom use (OR 3.31, p < .001). We also found a
      significant relationship between exposure to DiC activities and outreach and HIV
      testing in Kunming (OR 2.92, p < .01) and exposure to peer-led outreach and HIV
      testing through referrals in Gejiu, Nanning, and Luzhai (OR 3.63, p < .05).
      CONCLUSIONS: A comprehensive harm reduction model delivered through peer-led and
      community-based strategies reduced HIV risk among PWID in China. Both DiC
      activities and outreach were effective in providing PWID behavior change
      communications (BCC) and HTC. HTC is best offered in settings like DiCs, where
      there is privacy for testing and receiving results. Outreach coverage was low,
      especially in Guangxi province where the implementation model required building
      the technical capacity of government partners and grassroot organizations.
      Outreach appears to be most effective for referring PWID into HTC, especially
      when DiC-based HTC is not available and increasing awareness of DiCs where PWID
      can receive more intensive BCC interventions.

PMID- 24885779
TI  - Internet-based cognitive bias modification for obsessive compulsive disorder:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Cognitive bias modification (CBM) interventions have demonstrated
      efficacy in augmenting core biases implicated in psychopathology. The current
      randomized controlled trial (RCT) will evaluate the efficacy of an internet
      delivered positive imagery cognitive bias modification intervention for obsessive
      compulsive disorder (OCD) when compared to a control condition. METHODS/DESIGN:
      Patients meeting diagnostic criteria for a current or lifetime diagnosis of OCD
      will be recruited via the research arm of a not-for-profit clinical and research
      unit in Australia. The minimum sample size for each group (alpha set at 0.05,
      power at .80) was identified as 29, but increased to 35 to allow for 20%
      attrition. We will measure the impact of CBM on interpretations bias using the OC
      Bias Measure (The Ambiguous Scenarios Test for OCD ;AST-OCD) and OC-beliefs (The
      Obsessive Beliefs Questionnaire-TRIP; OBQ-TRIP). Secondary outcome measures
      include the Dimensional Obsessive-Compulsive Scale (DOCS), the Patient Health
      Questionnaire (PHQ-9), The Kessler Psychological Distress Scale (K10), and the
      Word Sentence Association Test for OCD (WSAO). Change in diagnostic status will
      be indexed using the OCD Mini International Neuropsychiatric Interview (M.I.N.I)
      Module at baseline and follow-up. Intent-to-treat (ITT) marginal and mixed-effect
      models using restricted maximum likelihood (REML) estimation will be used to
      evaluate the primary hypotheses. Stability of bias change will be assessed at 1
      month follow-up. DISCUSSION: A limitation of the online nature of the study is
      the inability to include a behavioral outcome measure. TRIAL REGISTRATION: The
      trial was registered on 10 October 2013 with the Australian New Zealand Clinical
      Trials Registry (ACTRN12613001130752).

PMID- 24885780
TI  - Stabilization of perturbed Boolean network attractors through compensatory
      interactions.
AB  - BACKGROUND: Understanding and ameliorating the effects of network damage are of
      significant interest, due in part to the variety of applications in which network
      damage is relevant. For example, the effects of genetic mutations can cascade
      through within-cell signaling and regulatory networks and alter the behavior of
      cells, possibly leading to a wide variety of diseases. The typical approach to
      mitigating network perturbations is to consider the compensatory activation or
      deactivation of system components. Here, we propose a complementary approach
      wherein interactions are instead modified to alter key regulatory functions and
      prevent the network damage from triggering a deregulatory cascade. RESULTS: We
      implement this approach in a Boolean dynamic framework, which has been shown to
      effectively model the behavior of biological regulatory and signaling networks.
      We show that the method can stabilize any single state (e.g., fixed point
      attractors or time-averaged representations of multi-state attractors) to be an
      attractor of the repaired network. We show that the approach is minimalistic in
      that few modifications are required to provide stability to a chosen attractor
      and specific in that interventions do not have undesired effects on the
      attractor. We apply the approach to random Boolean networks, and further show
      that the method can in some cases successfully repair synchronous limit cycles.
      We also apply the methodology to case studies from drought-induced signaling in
      plants and T-LGL leukemia and find that it is successful in both stabilizing
      desired behavior and in eliminating undesired outcomes. Code is made freely
      available through the software package BooleanNet. CONCLUSIONS: The methodology
      introduced in this report offers a complementary way to manipulating node
      expression levels. A comprehensive approach to evaluating network manipulation
      should take an "all of the above" perspective; we anticipate that theoretical
      studies of interaction modification, coupled with empirical advances, will
      ultimately provide researchers with greater flexibility in influencing system
      behavior.

PMID- 24885782
TI  - QGRS-Conserve: a computational method for discovering evolutionarily conserved G
      quadruplex motifs.
AB  - BACKGROUND: Nucleic acids containing guanine tracts can form quadruplex
      structures via non-Watson-Crick base pairing. Formation of G-quadruplexes is
      associated with the regulation of important biological functions such as
      transcription, genetic instability, DNA repair, DNA replication, epigenetic
      mechanisms, regulation of translation, and alternative splicing. G-quadruplexes
      play important roles in human diseases and are being considered as targets for a
      variety of therapies. Identification of functional G-quadruplexes and the study
      of their overall distribution in genomes and transcriptomes is an important
      pursuit. Traditional computational methods map sequence motifs capable of forming
      G-quadruplexes but have difficulty in distinguishing motifs that occur by chance
      from ones which fold into G-quadruplexes. RESULTS: We present Quadruplex forming
      'G'-rich sequences (QGRS)-Conserve, a computational method for calculating motif
      conservation across exomes and supports filtering to provide researchers with
      more precise methods of studying G-quadruplex distribution patterns. Our method
      quantitatively evaluates conservation between quadruplexes found in homologous
      nucleotide sequences based on several motif structural characteristics. QGRS
      Conserve also efficiently manages overlapping G-quadruplex sequences such that
      the resulting datasets can be analyzed effectively. CONCLUSIONS: We have applied
      QGRS-Conserve to identify a large number of G-quadruplex motifs in the human
      exome conserved across several mammalian and non-mammalian species. We have
      successfully identified multiple homologs of many previously published G
      quadruplexes that play post-transcriptional regulatory roles in human genes.
      Preliminary large-scale analysis identified many homologous G-quadruplexes in the
      5'- and 3'-untranslated regions of mammalian species. An expectedly smaller set
      of G-quadruplex motifs was found to be conserved across larger phylogenetic
      distances. QGRS-Conserve provides means to build datasets that can be filtered
      and categorized in a variety of biological dimensions for more targeted studies
      in order to better understand the roles that G-quadruplexes play.

PMID- 24885781
TI  - Impact of carbon nanotubes and graphene on immune cells.
AB  - It has been recently proposed that nanomaterials, alone or in concert with their
      specific biomolecular conjugates, can be used to directly modulate the immune
      system, therefore offering a new tool for the enhancement of immune-based
      therapies against infectious disease and cancer. Here, we revised the
      publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene
      and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most
      widely investigated, we noticed a progressive increase of studies focusing on
      graphene in the last couple of years. The majority of the works (56%) have been
      carried out on macrophages, following by lymphocytes (30% of the studies). In the
      case of lymphocytes, T cells were the most investigated (22%) followed by
      monocytes and dendritic cells (7%), mixed cell populations (peripheral blood
      mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the
      studies focused on toxicity and biocompatibility, while mechanistic insights on
      the effect of carbon nanotubes on immune cells are generally lacking. Only very
      recently high-throughput gene-expression analyses have shed new lights on
      unrecognized effects of carbon nanomaterials on the immune system. These
      investigations have demonstrated that some f-CNTs can directly elicitate specific
      inflammatory pathways. The interaction of graphene with the immune system is
      still at a very early stage of investigation. This comprehensive state of the art
      on biocompatible f-CNTs and graphene on immune cells provides a useful compass to
      guide future researches on immunological applications of carbon nanomaterials in
      medicine. 

PMID- 24885783
TI  - Alterations in mosquito behaviour by malaria parasites: potential impact on force
      of infection.
AB  - BACKGROUND: A variety of studies have reported that malaria parasites alter the
      behaviour of mosquitoes. These behavioural alterations likely increase
      transmission because they reduce the risk of vector death during parasite
      development and increase biting after parasites become infectious. METHODS: A
      mathematical model is used to investigate the potential impact of these
      behavioural alterations on the lifetime number of infectious bites delivered. The
      model is used to explore the importance of assumptions about the magnitude and
      distribution of mortality as well as the importance of extrinsic incubation
      period and gonotrophic cycle length. Additionally, the model is applied to four
      datasets taken from actual transmission settings. RESULTS: The impact of
      behavioural changes on the relative number of lifetime bites is highly dependent
      on assumptions about the distribution of mortality over the mosquito-feeding
      cycle. Even using fairly conservative estimates of these parameters and field
      collected data, the model outputs suggest that altered feeding could easily cause
      a doubling in the force of infection. CONCLUSIONS: Infection-induced behavioural
      alterations have their greatest impact on the lifetime number of infectious bites
      in environments with high feeding-related adult mortality and many pre-infectious
      feeding cycles. Interventions that increase feeding-associated mortality are
      predicted to amplify the relative fitness benefits and hence enhance the strength
      of selection for behavioural alteration.

PMID- 24885784
TI  - Disruption of Mycobacterium avium subsp. paratuberculosis-specific genes impairs
      in vivo fitness.
AB  - BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP) is an obligate
      intracellular pathogen that infects many ruminant species. The acquisition of
      foreign genes via horizontal gene transfer has been postulated to contribute to
      its pathogenesis, as these genetic elements are absent from its putative
      ancestor, M. avium subsp. hominissuis (MAH), an environmental organism with
      lesser pathogenicity. In this study, high-throughput sequencing of MAP transposon
      libraries were analyzed to qualitatively and quantitatively determine the
      contribution of individual genes to bacterial survival during infection. RESULTS:
      Out of 52384 TA dinucleotides present in the MAP K-10 genome, 12607 had a
      MycoMarT7 transposon in the input pool, interrupting 2443 of the 4350 genes in
      the MAP genome (56%). Of 96 genes situated in MAP-specific genomic islands, 82
      were disrupted in the input pool, indicating that MAP-specific genomic regions
      are dispensable for in vitro growth (odds ratio = 0.21). Following 5 independent
      in vivo infections with this pool of mutants, the correlation between output
      pools was high for 4 of 5 (R = 0.49 to 0.61) enabling us to define genes whose
      disruption reproducibly reduced bacterial fitness in vivo. At three different
      thresholds for reduced fitness in vivo, MAP-specific genes were over-represented
      in the list of predicted essential genes. We also identified additional genes
      that were severely depleted after infection, and several of them have orthologues
      that are essential genes in M. tuberculosis. CONCLUSIONS: This work indicates
      that the genetic elements required for the in vivo survival of MAP represent a
      combination of conserved mycobacterial virulence genes and MAP-specific genes
      acquired via horizontal gene transfer. In addition, the in vitro and in vivo
      essential genes identified in this study may be further characterized to offer a
      better understanding of MAP pathogenesis, and potentially contribute to the
      discovery of novel therapeutic and vaccine targets.

PMID- 24885785
TI  - Positive practice environments influence job satisfaction of primary health care
      clinic nursing managers in two South African provinces.
AB  - BACKGROUND: Nurses constitute the majority of the health workforce in South
      Africa and they play a major role in providing primary health care (PHC)
      services. Job satisfaction influences nurse retention and successful
      implementation of health system reforms. This study was conducted in light of
      renewed government commitment to reforms at the PHC level, and to contribute to
      the development of solutions to the challenges faced by the South African nursing
      workforce. The objective of the study was to determine overall job satisfaction
      of PHC clinic nursing managers and the predictors of their job satisfaction in
      two South African provinces. METHODS: During 2012, a cross-sectional study was
      conducted in two South African provinces. Stratified random sampling was used to
      survey a total of 111 nursing managers working in PHC clinics. These managers
      completed a pre-tested Measure of Job Satisfaction questionnaire with subscales
      on personal satisfaction, workload, professional support, training, pay, career
      prospects and standards of care. Mean scores were used to measure overall job
      satisfaction and various subscales. Predictors of job satisfaction were
      determined through multiple logistic regression analysis. RESULTS: A total of 108
      nursing managers completed the survey representing a 97% response rate. The mean
      age of respondents was 49 years (SD = 7.9) and the majority of them (92%) were
      female. Seventy-six percent had a PHC clinical training qualification. Overall
      mean job satisfaction scores were 142.80 (SD = 24.3) and 143.41 (SD = 25.6) for
      Gauteng and Free State provinces respectively out of a maximum possible score of
      215. Predictors of job satisfaction were: working in a clinic of choice (RRR =
      3.10 (95% CI: 1.11 to 8.62, P = 0.030)), being tired at work (RRR = 0.19 (95% CI:
      0.08 to 0.50, P = 0.001)) and experience of verbal abuse (RRR = 0.18 (95% CI:
      0.06 to 0.55, P = 0.001). CONCLUSION: Allowing nurses greater choice of clinic to
      work in, the prevention of violence and addressing workloads could improve the
      practice environment and job satisfaction of PHC clinic nursing managers.

PMID- 24885786
TI  - Predictors of HIV prevalence among street-based female sex workers in Andhra
      Pradesh state of India: a district-level analysis.
AB  - BACKGROUND: A decline in HIV prevalence among female sex workers (FSWs) has been
      reported from the Indian state of Andhra Pradesh between the two rounds of
      integrated biological and behavioural assessment (IBBA) surveys in 2005-06 and
      2009, the first of these around the time of start of the Avahan HIV prevention
      intervention. In order to facilitate further planning of FSW interventions, we
      report the factors associated with HIV prevalence among street-based FSWs.
      METHODS: Behavioural data from the two rounds of IBBA surveys, district-level FSW
      HIV prevention program data, and urbanisation data from the Census of India were
      utilized. A multilevel logistic model was used to investigate factors associated
      with inter-district variations in HIV positivity among street-based FSWs in the
      districts by fitting a two-level model. RESULTS: The estimated HIV prevalence
      among street-based FSWs changed from 16% (95% confidence interval [CI] 14.2 -
      17.7%) to 12.9% (95% CI 11.5 - 14.2%) from 2005-06 to 2009. HIV positivity was
      significantly higher in districts with a high proportion of FSWs registered with
      targeted interventions (odds ratio [OR] 2.02; 95% CI 1.18-3.45), and in districts
      with medium (OR 2.54; 95% CI 1.58-4.08) or high (OR 1.55; 95% CI 1.05-2.29)
      proportion of urban population. Districts which had met the condom requirement
      targets for FSWs had significantly lower HIV positivity (OR 0.50; 95% CI 0.26
      0.97). In round 2 survey, the districts with medium level urbanisation had
      significantly higher proportion of FSWs registered with HIV intervention
      programmes and also reported higher consistent condom use with regular partner (p
      < 0.001). CONCLUSIONS: Variations in HIV positivity among street-based FSWs were
      seen at the district level in relation to HIV intervention programs and the
      degree of urbanization. These findings could be used to enhance program planning
      to further reduce HIV transmission in this population.

PMID- 24885787
TI  - Dehydration stress memory genes of Zea mays; comparison with Arabidopsis
      thaliana.
AB  - BACKGROUND: Pre-exposing plants to diverse abiotic stresses may alter their
      physiological and transcriptional responses to a subsequent stress, suggesting a
      form of "stress memory". Arabidopsis thaliana plants that have experienced
      multiple exposures to dehydration stress display transcriptional behavior
      suggesting "memory" from an earlier stress. Genes that respond to a first stress
      by up-regulating or down-regulating their transcription but in a subsequent
      stress provide a significantly different response define the 'memory genes'
      category. Genes responding similarly to each stress form the 'non-memory'
      category. It is unknown whether such memory responses exists in other Angiosperm
      lineages and whether memory is an evolutionarily conserved response to repeated
      dehydration stresses. RESULTS: Here, we determine the transcriptional responses
      of maize (Zea mays L.) plants that have experienced repeated exposures to
      dehydration stress in comparison with plants encountering the stress for the
      first time. Four distinct transcription memory response patterns similar to those
      displayed by A. thaliana were revealed. The most important contribution is the
      evidence that monocot and eudicot plants, two lineages that have diverged 140 to
      200 M years ago, display similar abilities to 'remember' a dehydration stress and
      to modify their transcriptional responses, accordingly. The highly sensitive RNA
      Seq analyses allowed to identify genes that function similarly in the two
      lineages, as well as genes that function in species-specific ways. Memory
      transcription patterns indicate that the transcriptional behavior of responding
      genes under repeated stresses is different from the behavior during an initial
      dehydration stress, suggesting that stress memory is a complex phenotype
      resulting from coordinated responses of multiple signaling pathways. CONCLUSIONS:
      Structurally related genes displaying the same memory responses in the two
      species would suggest conservation of the genes' memory during the evolution of
      plants' dehydration stress response systems. On the other hand, divergent
      transcription memory responses by genes encoding similar functions would suggest
      occurrence of species-specific memory responses. The results provide novel
      insights into our current knowledge of how plants respond to multiple dehydration
      stresses, as compared to a single exposure, and may serve as a reference platform
      to study the functions of memory genes in adaptive responses to water deficit in
      monocot and eudicot plants.

PMID- 24885788
TI  - Molecular characterization of Clonorchis sinensis secretory myoglobin:
      delineating its role in anti-oxidative survival.
AB  - BACKGROUND: Clonorchiasis is a globally important, neglected food-borne disease
      caused by Clonorchis sinensis (C. sinensis), and it is highly related to
      cholangiocarcinoma and hepatocellular carcinoma. Increased molecular evidence has
      strongly suggested that the adult worm of C. sinensis continuously releases
      excretory-secretory proteins (ESPs), which play important roles in the parasite
      host interactions, to establish successful infection and ensure its own survival.
      Myoglobin, a hemoprotein, is present in high concentrations in trematodes and
      ESPs. To further understand the biological function of CsMb and its putative
      roles in the interactions of C. sinensis with its host, we explored the molecular
      characterization of CsMb in this paper. METHODS: We expressed CsMb and its
      mutants in E. coli BL21 and identified its molecular characteristics using
      bioinformatics analysis and experimental approaches. Reverse transcription PCR
      analysis was used to measure myoglobin transcripts of C. sinensis with different
      culture conditions. The peroxidase activity of CsMb was confirmed by
      spectrophotometry. We co-cultured RAW264.7 cells with recombinant CsMb (rCsMb),
      and we then measured the production of hydrogen peroxide (H2O2) and nitric oxide
      (NO) in addition to the mRNA levels of inducible nitric oxide synthase (iNOS), Cu
      Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) in activated
      RAW264.7 cells. RESULTS: In the in vitro culture of adult worms, the transcripts
      of CsMb increased with the increase of oxygen content. Oxidative stress
      conditions induced by H2O2 increased the levels of CsMb transcripts in a dose
      dependent manner. Furthermore, CsMb catalyzed oxidation reactions in the presence
      of H2O2, and amino acid 34 of CsMb played an essential role in its reaction with
      H2O2. In addition, CsMb significantly reduced H2O2 and NO levels in LPS-activated
      macrophages, and CsMb downregulated iNOS and SOD expression in activated
      macrophages. CONCLUSION: The present study is the first to investigate the
      peroxidase activity of CsMb. This investigation suggested that C. sinensis may
      decrease the redox activation of macrophages by CsMb expression to evade host
      immune responses. These studies contribute to a better understanding of the role
      of CsMb in the molecular mechanisms involved in ROS detoxification by C.
      sinensis.

PMID- 24885789
TI  - Guidance and examination by ultrasound versus landmark and radiographic method
      for placement of subclavian central venous catheters: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Central venous catheters play an important role in patient care. Real
      time ultrasound-guided subclavian central venous (SCV) cannulation may reduce the
      incidence of complications and the time between skin penetration and the
      aspiration of venous blood into the syringe. Ultrasonic diagnosis of catheter
      misplacement and pneumothorax related to central venous catheterization is rapid
      and accurate. It is unclear, however, whether ultrasound real-time guidance and
      examination can reduce procedure times and complication rates when compared with
      landmark guidance and radiographic examination for SCV catheterization.
      METHODS/DESIGN: The Subclavian Central Venous Catheters Guidance and Examination
      by UltraSound (SUBGEUS) study is an investigator-initiated single center,
      randomized, controlled two-arm trial. Three hundred patients undergoing SCV
      catheter placement will be randomized to ultrasound real-time guidance and
      examination or landmark guidance and radiographic examination. The primary
      outcome is the time between the beginning of the procedure and control of the
      catheter. Secondary outcomes include the times required for the six components of
      the total procedure, the occurrence of complications (pneumothorax, hemothorax,
      or misplacement), failure of the technique and occurrence of central venous
      catheter infections. DISCUSSION: The SUBGEUS trial is the first randomized
      controlled study to investigate whether ultrasound real-time guidance and
      examination for SCV catheter placement reduces all procedure times and the rate
      of complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01888094.

PMID- 24885791
TI  - A prospective follow-up study on transmission of Campylobacter from poultry to
      abattoir workers.
AB  - Contact with poultry or poultry meat is a well-known risk factor for
      campylobacteriosis, but prospective studies on transmission of Campylobacter from
      chickens to humans during slaughter are scarce. In this study, we monitored
      transmission of Campylobacter from slaughtered chicken to originally culture
      negative abattoir workers during the peak season of colonized chicken and human
      Campylobacter infection. Stool samples were obtained from 28 abattoir workers
      together with data on health status once a month between June and September 2010,
      with a follow-up sample collected in February 2011. Campylobacter-positive
      individuals and chicken flocks were identified by culture, and isolates were
      further characterized using molecular techniques. Campylobacter was isolated from
      seven asymptomatic individuals. Four of them had been newly employed and had not
      reported any previous Campylobacter infection. Four human isolates had matching
      genetic fingerprints with isolates from recently slaughtered chickens. Our
      results further support the role of chicken as the source of human Campylobacter
      infection but suggest that asymptomatic Campylobacter infection may occur even in
      individuals with only limited earlier exposure to Campylobacter.

PMID- 24885792
TI  - Mycobacterial infection of breast prosthesis--a conservative treatment: a case
      report.
AB  - BACKGROUND: Bacterial infection is a well-known risk of breast implant surgery.
      It is typically caused by bacterial skin flora, specifically Staphylococcus
      aureus and the coagulase negative staphylococci. There have been infrequent
      reports of breast implant infection caused by the atypical mycobacteria, of which
      Mycobacterium canariasense not yet reported in the literature. CASE PRESENTATION:
      This report summarizes the case of a female patient who underwent mastectomy
      followed by bilateral breast augmentation and presented approximately three years
      later with clinical evidence of infected breast prosthesis by Mycobacterium
      canariasense. One year after thoroughly follow-up, appropriate antibiotherapy and
      the change of the infected prosthesis, the patient presented no signs of
      reinfection. CONCLUSION: Our case demonstrates that Mycobacterium canariasense
      should be considered as a new potential cause of infected breast prosthesis.

PMID- 24885790
TI  - AIDS and non-AIDS severe morbidity associated with hospitalizations among HIV
      infected patients in two regions with universal access to care and antiretroviral
      therapy, France and Brazil, 2000-2008: hospital-based cohort studies.
AB  - BACKGROUND: In high-income settings, the spectrum of morbidity and mortality
      experienced by Human Immunodeficiency Virus (HIV)-infected individuals receiving
      combination antiretroviral therapy (cART) has switched from predominantly AIDS
      related to non-AIDS-related conditions. In the context of universal access to
      care, we evaluated whether that shift would apply in Brazil, a middle-income
      country with universal access to treatment, as compared to France. METHODS: Two
      hospital-based cohorts of HIV-infected individuals were used for this analysis:
      the ANRS CO3 Aquitaine Cohort in South Western France and the Evandro Chagas
      Research Institute (IPEC) Cohort of the Oswaldo Cruz Foundation in Rio de
      Janeiro, Brazil. Severe morbid events (AIDS- and non-AIDS-related) were defined
      as all clinical diagnoses associated with a hospitalization of >=48 hours. Trends
      in the incidence rate of events and their determinants were estimated while
      adjusting for within-subject correlation using generalized estimating equations
      models with an auto-regressive correlation structure and robust standard errors.
      RESULT: Between January 2000 and December 2008, 7812 adult patients were followed
      for a total of 41,668 person-years (PY) of follow-up. Throughout the study
      period, 90% of the patients were treated with cART. The annual incidence rate of
      AIDS and non-AIDS events, and of deaths significantly decreased over the years,
      from 6.2, 21.1, and 1.9 AIDS, non-AIDS events, and deaths per 100 PY in 2000 to
      4.3, 14.9, and 1.5/100 PY in 2008. The annual incidence rates of non-AIDS events
      surpassed that of AIDS-events during the entire study period. High CD4 cell
      counts were associated with a lower incidence rate of AIDS and non-AIDS events as
      well as with lower rates of specific non-AIDS events, such as bacterial, hepatic,
      viral, neurological, and cardiovascular conditions. Adjusted analysis showed that
      severe morbidity was associated with lower CD4 counts and higher plasma HIV RNAs
      but not with setting (IPEC versus Aquitaine). CONCLUSIONS: As information on
      severe morbidities for HIV-infected patients remain scarce, data on
      hospitalizations are valuable to identify priorities for case management and to
      improve the quality of life of patients with a chronic disease requiring life
      long treatment. Immune restoration is highly effective in reducing AIDS and non
      AIDS severe morbid events irrespective of the setting.

PMID- 24885793
TI  - Live birth after fresh embryo transfer vs elective embryo cryopreservation/frozen
      embryo transfer in women with polycystic ovary syndrome undergoing IVF (FreFro
      PCOS): study protocol for a multicenter, prospective, randomized controlled
      clinical trial.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) patients are at increased risk of
      pregnancy complications, which may impair pregnancy outcome. Transfer of fresh
      embryos after superovulation may lead to abnormal implantation and placentation
      and further increase risk for pregnancy loss and complications. Some preliminary
      data suggest that elective embryo cryopreservation followed by frozen-thawed
      embryo transfer into a hormonally primed endometrium could result in a higher
      clinical pregnancy rate than that achieved by fresh embryo transfer.
      METHODS/DESIGN: This study is a multicenter, prospective, randomized controlled
      clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo
      transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle
      of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be
      enrolled and randomized into two parallel groups. Participants in group A will
      undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants
      in group B will undergo elective embryo cryopreservation after oocyte retrieval
      and frozen-thawed embryo transfer in programmed cycles. The primary outcome is
      the live birth rate. Our study is powered at 80 to detect an absolute difference
      of 10 at the significance level of 0.01 based on a two-sided test. DISCUSSION: We
      hypothesize that elective embryo cryopreservation and frozen-thawed embryo
      transfer will reduce the incidence of pregnancy complications and increase the
      live birth rate in PCOS patients who need IVF to achieve pregnancy. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01841528.

PMID- 24885795
TI  - Cucurbitacin-E inhibits multiple cancer cells proliferation through attenuation
      of Wnt/beta-catenin signaling.
AB  - Recent studies suggest that the use of cucurbitacins could inhibit cancer cell
      progression. In the current study, the authors analyzed the effect of
      cucurbitacin-E (CuE) in cancer cells using A549, Hep3B, and SW480 cells. The
      authors found that CuE inhibited cell proliferation and modulated the expression
      of cell cycle regulators in these cells. Moreover, the authors found that CuE
      inhibited Wnt/beta-catenin signaling activation through upregulation of tumor
      suppressor Menin. Indeed, ablation of Menin using small interfering RNA (siRNA)
      oligos attenuated the antiproliferative roles of CuE. Taken together, the results
      of this study provide a novel mechanism that may contribute to the antineoplastic
      effects of CuE in cancer cells.

PMID- 24885794
TI  - Hypermethylation and down-regulation of DLEU2 in paediatric acute myeloid
      leukaemia independent of embedded tumour suppressor miR-15a/16-1.
AB  - BACKGROUND: Acute Myeloid Leukaemia (AML) is a highly heterogeneous disease.
      Studies in adult AML have identified epigenetic changes, specifically DNA
      methylation, associated with leukaemia subtype, age of onset and patient survival
      which highlights this heterogeneity. However, only limited DNA methylation
      studies have elucidated any associations in paediatric AML. METHODS: We
      interrogated DNA methylation on a cohort of paediatric AML FAB subtype M5
      patients using the Illumina HumanMethylation450 (HM450) BeadChip, identifying a
      number of target genes with p <0.01 and Deltabeta >0.4 between leukaemic and
      matched remission (n = 20 primary leukaemic, n = 13 matched remission). Amongst
      those genes identified, we interrogate DLEU2 methylation using locus-specific
      SEQUENOM MassARRAY(r) EpiTYPER(r) and an increased validation cohort (n = 28
      primary leukaemic, n = 14 matched remission, n = 17 additional non-leukaemic and
      cell lines). Following methylation analysis, expression studies were undertaken
      utilising the same patient samples for singleplex TaqMan gene and miRNA assays
      and relative expression comparisons. RESULTS: We identified differential DNA
      methylation at the DLEU2 locus, encompassing the tumour suppressor microRNA miR
      15a/16-1 cluster. A number of HM450 probes spanning the DLEU2/Alt1
      Transcriptional Start Site showed increased levels of methylation in leukaemia
      (average over all probes >60%) compared to disease-free haematopoietic cells and
      patient remission samples (<24%) (p < 0.001). Interestingly, DLEU2 mRNA down
      regulation in leukaemic patients (p < 0.05) was independent of the embedded
      mature miR-15a/16-1 expression. To assess prognostic significance of DLEU2 DNA
      methylation, we stratified paediatric AML patients by their methylation status. A
      subset of patients recorded methylation values for DLEU2 akin to non-leukaemic
      specimens, specifically patients with sole trisomy 8 and/or chromosome 11
      abnormalities. These patients also showed similar miR-15a/16-1 expression to non
      leukaemic samples, and potential improved disease prognosis. CONCLUSIONS: The
      DLEU2 locus and embedded miRNA cluster miR-15a/16-1 is commonly deleted in adult
      cancers and shown to induce leukaemogenesis, however in paediatric AML we found
      the region to be transcriptionally repressed. In combination, our data highlights
      the utility of interrogating DNA methylation and microRNA in combination with
      underlying genetic status to provide novel insights into AML biology.

PMID- 24885797
TI  - Anomalous origin of the left coronary artery from the pulmonary artery presenting
      as dilated cardiomyopathy: a case report.
AB  - INTRODUCTION: Anomalous origin of the left coronary artery from the pulmonary
      artery is a rare congenital anomaly and one of the causes of myocardial ischemia.
      The usual clinical course is severe left-sided heart failure and mitral valve
      insufficiency presenting during the first months of life. CASE PRESENTATION: We
      report the case of a 6-month-old Tunisian girl who presented with dilated
      cardiomyopathy. Echocardiography suspected anomalous origin of the left coronary
      artery. The definitive diagnosis of anomalous origin of the left coronary artery
      from the pulmonary artery was reached by multislice computed tomography and
      coronary angiography. CONCLUSION: In cases of dilated cardiomyopathy, anomalous
      origin of the left coronary artery from the pulmonary artery syndrome has to be
      kept in mind as a surgically correctable cause.

PMID- 24885796
TI  - Comparison of strand-specific transcriptomes of enterohemorrhagic Escherichia
      coli O157:H7 EDL933 (EHEC) under eleven different environmental conditions
      including radish sprouts and cattle feces.
AB  - BACKGROUND: Multiple infection sources for enterohemorrhagic Escherichia coli
      O157:H7 (EHEC) are known, including animal products, fruit and vegetables. The
      ecology of this pathogen outside its human host is largely unknown and one third
      of its annotated genes are still hypothetical. To identify genetic determinants
      expressed under a variety of environmental factors, we applied strand-specific
      RNA-sequencing, comparing the SOLiD and Illumina systems. RESULTS: Transcriptomes
      of EHEC were sequenced under 11 different biotic and abiotic conditions: LB
      medium at pH4, pH7, pH9, or at 15 degrees C; LB with nitrite or trimethoprim
      sulfamethoxazole; LB-agar surface, M9 minimal medium, spinach leaf juice, surface
      of living radish sprouts, and cattle feces. Of 5379 annotated genes in strain
      EDL933 (genome and plasmid), a surprising minority of only 144 had null
      sequencing reads under all conditions. We therefore developed a statistical
      method to distinguish weakly transcribed genes from background transcription. We
      find that 96% of all genes and 91.5% of the hypothetical genes exhibit a
      significant transcriptional signal under at least one condition. Comparing SOLiD
      and Illumina systems, we find a high correlation between both approaches for fold
      changes of the induced or repressed genes. The pathogenicity island LEE showed
      highest transcriptional activity in LB medium, minimal medium, and after
      treatment with antibiotics. Unique sets of genes, including many hypothetical
      genes, are highly up-regulated on radish sprouts, cattle feces, or in the
      presence of antibiotics. Furthermore, we observed induction of the shiga-toxin
      carrying phages by antibiotics and confirmed active biofilm related genes on
      radish sprouts, in cattle feces, and on agar plates. CONCLUSIONS: Since only a
      minority of genes (2.7%) were not active under any condition tested (null reads),
      we suggest that the assumption of significant genome over-annotations is wrong.
      Environmental transcriptomics uncovered hitherto unknown gene functions and
      unique regulatory patterns in EHEC. For instance, the environmental function of
      azoR had been elusive, but this gene is highly active on radish sprouts. Thus,
      NGS-transcriptomics is an appropriate technique to propose new roles of
      hypothetical genes and to guide future research.

PMID- 24885799
TI  - Development of health risk-based metrics for defining a heatwave: a time series
      study in Brisbane, Australia.
AB  - BACKGROUND: This study attempted to develop health risk-based metrics for
      defining a heatwave in Brisbane, Australia. METHODS: Poisson generalised additive
      model was performed to assess the impact of heatwaves on mortality and emergency
      hospital admissions (EHAs) in Brisbane. RESULTS: In general, the higher the
      intensity and the longer the duration of a heatwave, the greater the health
      impacts. There was no apparent difference in EHAs risk during different periods
      of a warm season. However, there was a greater risk for mortality in the 2nd half
      of a warm season than that in the 1st half. While elderly (>=75 years) were
      particularly vulnerable to both the EHA and mortality effects of a heatwave, the
      risk for EHAs also significantly increased for two other age groups (0-64 years
      and 65-74 years) during severe heatwaves. Different patterns between
      cardiorespiratory mortality and EHAs were observed. Based on these findings, we
      propose the use of a tiered heat warning system based on the health risk of
      heatwave. CONCLUSIONS: Health risk-based metrics are a useful tool for the
      development of local heatwave definitions. This tool may have significant
      implications for the assessment of heatwave-related health consequences and
      development of heatwave response plans and implementation strategies.

PMID- 24885798
TI  - Resistance to Botrytis cinerea in Solanum lycopersicoides involves widespread
      transcriptional reprogramming.
AB  - BACKGROUND: Tomato (Solanum lycopersicum), one of the world's most important
      vegetable crops, is highly susceptible to necrotrophic fungal pathogens such as
      Botrytis cinerea and Alternaria solani. Improving resistance through conventional
      breeding has been hampered by a shortage of resistant germplasm and difficulties
      in introgressing resistance into elite germplasm without linkage drag. The goal
      of this study was to explore natural variation among wild Solanum species to
      identify new sources of resistance to necrotrophic fungi and dissect mechanisms
      underlying resistance against B. cinerea. RESULTS: Among eight wild species
      evaluated for resistance against B. cinerea and A. solani, S. lycopersicoides
      expressed the highest levels of resistance against both pathogens. Resistance
      against B. cinerea manifested as containment of pathogen growth. Through next
      generation RNA sequencing and de novo assembly of the S. lycopersicoides
      transcriptome, changes in gene expression were analyzed during pathogen
      infection. In response to B. cinerea, differentially expressed transcripts
      grouped into four categories: genes whose expression rapidly increased then
      rapidly decreased, genes whose expression rapidly increased and plateaued, genes
      whose expression continually increased, and genes with decreased expression.
      Homology-based searches also identified a limited number of highly expressed B.
      cinerea genes. Almost immediately after infection by B. cinerea, S.
      lycopersicoides suppressed photosynthesis and metabolic processes involved in
      growth, energy generation, and response to stimuli, and simultaneously induced
      various defense-related genes, including pathogenesis-related protein 1 (PR1), a
      beta-1,3-glucanase (glucanase), and a subtilisin-like protease, indicating a
      shift in priority towards defense. Moreover, cluster analysis revealed novel,
      uncharacterized genes that may play roles in defense against necrotrophic fungal
      pathogens in S. lycopersicoides. The expression of orthologous defense-related
      genes in S. lycopersicum after infection with B. cinerea revealed differences in
      the onset and intensity of induction, thus illuminating a potential mechanism
      explaining the increased susceptibility. Additionally, metabolic pathway analyses
      identified putative defense-related categories of secondary metabolites.
      CONCLUSIONS: In sum, this study provided insight into resistance against
      necrotrophic fungal pathogens in the Solanaceae, as well as novel sequence
      resources for S. lycopersicoides.

PMID- 24885800
TI  - Organizational impact of evidence-informed decision making training initiatives:
      a case study comparison of two approaches.
AB  - BACKGROUND: The impact of efforts by healthcare organizations to enhance the use
      of evidence to improve organizational processes through training programs has
      seldom been assessed. We therefore endeavored to assess whether and how the
      training of mid- and senior-level healthcare managers could lead to
      organizational change. METHODS: We conducted a theory-driven evaluation of the
      organizational impact of healthcare leaders' participation in two training
      programs using a logic model based on Nonaka's theory of knowledge conversion. We
      analyzed six case studies nested within the two programs using three embedded
      units of analysis (individual, group and organization). Interviews were conducted
      during intensive one-week data collection site visits. A total of 84 people were
      interviewed. RESULTS: We found that the impact of training could primarily be
      felt in trainees' immediate work environments. The conversion of attitudes was
      found to be easier to achieve than the conversion of skills. Our results show
      that, although socialization and externalization were common in all cases, a lack
      of combination impeded the conversion of skills. We also identified several
      individual, organizational and program design factors that facilitated and/or
      impeded the dissemination of the attitudes and skills gained by trainees to other
      organizational members. CONCLUSIONS: Our theory-driven evaluation showed that
      factors before, during and after training can influence the extent of skills and
      knowledge transfer. Our evaluation went further than previous research by
      revealing the influence--both positive and negative--of specific organizational
      factors on extending the impact of training programs.

PMID- 24885801
TI  - Successful treatment of posttraumatic phlegmasia cerulea dolens by reconstructing
      the external iliac vein: a case report.
AB  - INTRODUCTION: Phlegmasia cerulea dolens is a rare condition caused by complete
      venous occlusion leading to impaired arterial flow. To prevent progression to
      limb gangrene, prompt diagnosis and treatment initiation are paramount. Here we
      report a rare case of posttraumatic phlegmasia cerulea dolens after ligation of
      the iliac vein to save the patient's life, with successful treatment by
      reconstructing the external iliac vein. This is the first report of posttraumatic
      phlegmasia cerulea dolens induced by iliac vein ligation. CASE PRESENTATION: A 49
      year-old Chinese man was admitted to a local hospital for severe knife trauma
      with massive intraperitoneal bleeding. During exploratory laparotomy, he was
      diagnosed with traumatic rupture of his left external iliac vein without injury
      to the iliac artery. The proximal and distal parts of his injured external iliac
      vein were ligated to control the bleeding and rescue him, but his left leg
      quickly became severe swollen, cyanotic and pulseless. He was diagnosed with
      posttraumatic phlegmasia cerulea dolens after being transferred to our university
      hospital. After a retrievable filter was placed in his inferior vena cava via his
      right femoral vein, he underwent reopening of his abdomen followed by successful
      surgical reconstruction of his left iliac vein. He was treated with
      anticoagulation therapy postoperatively and his signs and symptoms improved
      markedly. He was discharged in a stable condition, with nearly full resolution of
      symptoms, 35 days after the operation. CONCLUSIONS: Our case demonstrates that
      ligation of an injured iliac vein may induce phlegmasia cerulea dolens in a
      posttraumatic scenario; prompt reconstruction of the iliac vein to restore the
      venous drainage is an effective treatment for phlegmasia cerulea dolens with
      impending gangrene.

PMID- 24885802
TI  - Bevacizumab terminates homeobox B9-induced tumor proliferation by silencing
      microenvironmental communication.
AB  - BACKGROUND: Homeobox B9 (HOXB9), a transcriptional factor, regulates
      developmental processes and tumor progression and has recently been recognized as
      one of important transcriptional factors related to angiogenesis. This study
      aimed to investigate the role of HOXB9 in tumorigenesis and angiogenesis.
      METHODS: We examined the expression of HOXB9 in colorectal cancer using qPCR and
      in situ hybridization. We also examined the effect of HOXB9 overexpression in
      colorectal cancer using a proliferation assay, ELISA, a multiplex assay, and
      xenograft models. The clinical significance of HOXB9 was statistically evaluated
      in resected specimens. RESULTS: HOXB9 was expressed in colorectal cancer
      specimens. HOXB9 induced angiogenesis and tumor proliferation in vitro, which
      resulted in high tumorigenicity in vivo and poor overall survival. Bevacizumab,
      an anti-vascular endothelial growth factor (VEGF) antibody, remarkably suppressed
      tumor proliferation by inhibiting angiogenesis in HOXB9-overexpressing
      xenografts, and it improved overall survival and provided prolonged progression
      free survival in HOXB9-overexpressing patients. A comprehensive multiplex assay
      of the supernatant of cancer cells co-cultured with human vascular endothelial
      cells and fibroblasts indicated significantly higher interleukin-6 (IL6) levels
      than those in the supernatant of monocultured cells. HOXB9 overexpression in
      clinical specimens was significantly correlated with increased IL6 expression. An
      IL6-neutralizing antibody inhibited VEGF secretion and tumor proliferation in the
      co-culture system. CONCLUSIONS: HOXB9 promotes the secretion of angiogenic
      factors, including VEGF, to induce tumor proliferation through microenvironmental
      production of cytokines including IL6 signaling. Moreover, silencing of VEGF or
      IL6 terminates cytokine release in tumor microenvironment. Thus, HOXB9 and IL6
      may be potential biomarkers for bevacizumab treatment.

PMID- 24885803
TI  - ALK rearrangement in a large series of consecutive non-small cell lung cancers:
      comparison between a new immunohistochemical approach and fluorescence in situ
      hybridization for the screening of patients eligible for crizotinib treatment.
AB  - CONTEXT: Echinoderm microtubule associated proteinlike 4-anaplastic lymphoma
      receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset
      of patients with non-small cell lung cancer (NSCLC) and has been shown to have
      oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect
      ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for
      routine application. OBJECTIVE: To evaluate the potential role of
      immunohistochemistry (IHC) as a screening tool to identify candidate cases for
      FISH analysis and for ALK inhibitor therapy in NSCLC. DESIGN: We performed FISH
      and IHC for ALK and mutational analysis for epidermal growth factor receptor
      (EGFR) and KRAS in 523 NSCLC specimens. We conducted IHC analysis with the
      monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly
      sensitive detection system. We also performed a MassARRAY-based analysis
      (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4
      ALK rearrangement. RESULTS: Of the 523 NSCLC specimens, 20 (3.8%) were positive
      for ALK rearrangement by FISH analysis. EGFR and KRAS mutations were identified
      in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK
      rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor
      samples analyzed, 18 (3.4%) were ALK(+) by IHC, 18 samples (3.4%) had concordant
      IHC and FISH results, and 2 ALK(+) cases (0.3%) by FISH failed to show ALK
      protein expression. In the 2 discrepant cases, we did not detect any mass peaks
      for the EML4-ALK variants by MassARRAY. CONCLUSIONS: Our results show that IHC
      may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis.

PMID- 24885805
TI  - Evidence in support of the role of disturbance vegetation for women's health and
      childcare in Western Africa.
AB  - BACKGROUND: In savannah-dominated Benin, West Africa, and forest-dominated Gabon,
      Central Africa, plants are a major source of healthcare for women and children.
      Due to this high demand and the reliance on wild populations as sources for
      medicinal plants, overharvesting of African medicinal plants is a common concern.
      Few studies in Western Africa, however, have assessed variations in harvest
      patterns across different ecological zones and within local communities. METHODS:
      We investigated which vegetation types women accessed to harvest medicinal plants
      by conducting 163 questionnaires with market vendors and women from urban and
      rural communities. We made botanical vouchers of cited species and collected
      information on their vegetation type and cultivation status. RESULTS: Secondary
      vegetation was a crucial asset; over 80% of the 335 Beninese and 272 Gabonese
      plant species came from disturbance vegetation and home gardens. In Benin, access
      to trade channels allowed female market vendors to use more vulnerable species
      than rural and urban women who harvested for personal use. In Gabon, no
      relationship was found between vulnerable plant use and informant type.
      CONCLUSIONS: This study highlights the underemphasized point that secondary
      vegetation is an asset for women and children's health in both savanna-dominated
      and forest-dominated landscapes. The use of disturbance vegetation demonstrates
      women's resilience in meeting healthcare needs in the limited amount of space
      that is available to them. Species of conservation concern included forest
      species and savanna trees sold at markets in Benin, especially Xylopia
      aethiopica, Khaya senegalensis, and Monodora myristica, and the timber trees with
      medicinal values in Gabon, such as Baillonella toxisperma.

PMID- 24885804
TI  - Multiple modes of proepicardial cell migration require heartbeat.
AB  - BACKGROUND: The outermost layer of the vertebrate heart, the epicardium, forms
      from a cluster of progenitor cells termed the proepicardium (PE). PE cells
      migrate onto the myocardium to give rise to the epicardium. Impaired epicardial
      development has been associated with defects in valve development, cardiomyocyte
      proliferation and alignment, cardiac conduction system maturation and adult heart
      regeneration. Zebrafish are an excellent model for studying cardiac development
      and regeneration; however, little is known about how the zebrafish epicardium
      forms. RESULTS: We report that PE migration occurs through multiple mechanisms
      and that the zebrafish epicardium is composed of a heterogeneous population of
      cells. Heterogeneity is first observed within the PE and persists through
      epicardium formation. Using in vivo imaging, histology and confocal microscopy,
      we show that PE cells migrate through a cellular bridge that forms between the
      pericardial mesothelium and the heart. We also observed the formation of PE
      aggregates on the pericardial surface, which were released into the pericardial
      cavity. It was previously reported that heartbeat-induced pericardiac fluid
      advections are necessary for PE cluster formation and subsequent epicardium
      development. We manipulated heartbeat genetically and pharmacologically and found
      that PE clusters clearly form in the absence of heartbeat. However, when
      heartbeat was inhibited the PE failed to migrate to the myocardium and the
      epicardium did not form. We isolated and cultured hearts with only a few
      epicardial progenitor cells and found a complete epicardial layer formed.
      However, pharmacologically inhibiting contraction in culture prevented epicardium
      formation. Furthermore, we isolated control and silent heart (sih) morpholino
      (MO) injected hearts prior to epicardium formation (60 hpf) and co-cultured these
      hearts with "donor" hearts that had an epicardium forming (108 hpf). Epicardial
      cells from donor hearts migrated on to control but not sih MO injected hearts.
      CONCLUSIONS: Epicardial cells stem from a heterogeneous population of
      progenitors, suggesting that the progenitors in the PE have distinct identities.
      PE cells attach to the heart via a cellular bridge and free-floating cell
      clusters. Pericardiac fluid advections are not necessary for the development of
      the PE cluster, however heartbeat is required for epicardium formation.
      Epicardium formation can occur in culture without normal hydrodynamic and
      hemodynamic forces, but not without contraction.

PMID- 24885806
TI  - Implementation of Cloud based next generation sequencing data analysis in a
      clinical laboratory.
AB  - BACKGROUND: The introduction of next generation sequencing (NGS) has
      revolutionized molecular diagnostics, though several challenges remain limiting
      the widespread adoption of NGS testing into clinical practice. One such
      difficulty includes the development of a robust bioinformatics pipeline that can
      handle the volume of data generated by high-throughput sequencing in a cost
      effective manner. Analysis of sequencing data typically requires a substantial
      level of computing power that is often cost-prohibitive to most clinical
      diagnostics laboratories. FINDINGS: To address this challenge, our institution
      has developed a Galaxy-based data analysis pipeline which relies on a web-based,
      cloud-computing infrastructure to process NGS data and identify genetic variants.
      It provides additional flexibility, needed to control storage costs, resulting in
      a pipeline that is cost-effective on a per-sample basis. It does not require the
      usage of EBS disk to run a sample. CONCLUSIONS: We demonstrate the validation and
      feasibility of implementing this bioinformatics pipeline in a molecular
      diagnostics laboratory. Four samples were analyzed in duplicate pairs and showed
      100% concordance in mutations identified. This pipeline is currently being used
      in the clinic and all identified pathogenic variants confirmed using Sanger
      sequencing further validating the software.

PMID- 24885807
TI  - The evolution of contact calls in isolated and overlapping populations of two
      white-eye congeners in East Africa (Aves, Zosterops).
AB  - BACKGROUND: Closely related species often occur in geographic isolation, yet
      sometimes form contact zones with the potential to hybridize. Pre-zygotic
      barriers may prevent cross breeding in such contact zones. In East Africa, White
      eye birds have evolved into various species, inhabiting different habitat types.
      Zosterops poliogaster is found in cool and moist cloud forests at higher
      elevations, whereas Z. abyssinicus is distributed across the dry and hot lowland
      savannahs. In most areas, these two species occur allopatrically, but in the
      contact zone where the mountain meets the savannah, the distributions of these
      species sometimes overlap (parapatry), and in a few areas the two taxa occur
      sympatrically. Acoustic communication is thought to be an important species
      recognition mechanism in birds and an effective prezygotic barrier for
      hybridisation. We recorded contact calls of both the lowland and highland species
      in (i) distinct populations (allopatry), (ii) along contact zones (parapatry),
      and (iii) in overlapping populations (sympatry) to test for species and
      population differentiation. RESULTS: We found significant differences in call
      characteristics between the highland and lowland species, in addition to call
      differentiation within species. The highland Z. poliogaster shows a strong call
      differentiation among local populations, accompanied by comparatively low
      variability in their contact calls within populations (i.e. a small acoustic
      space). In contrast, calls of the lowland Z. abyssinicus are not differentiated
      among local sites but show relatively high variability in calls within single
      populations. Call patterns in both species show geographic clines in relation to
      latitude and longitude. Calls from parapatric populations from both species
      showed greater similarity to the other taxon in comparison to heterospecific
      populations found in allopatry. However, where the two species occur
      sympatrically, contact calls of both species are more distinct from each other
      than in either allopatric or parapatric populations. CONCLUSION: The contrasting
      patterns reflect divergent spatial distributions: the highland Z. poliogaster
      populations are highly disjunct, while Z. abyssinicus lowland populations are
      interconnected. Higher similarity in contact calls of heterospecific populations
      might be due to intermixing. In contrast, sympatric populations show reproductive
      character displacement which leads to strongly divergent call patterns.

PMID- 24885808
TI  - Identification of serum biomarkers in dogs naturally infected with Babesia canis
      canis using a proteomic approach.
AB  - BACKGROUND: Canine babesiosis is a tick-borne disease that is caused by the
      haemoprotozoan parasites of the genus Babesia. There are limited data on serum
      proteomics in dogs, and none of the effect of babesiosis on the serum proteome.
      The aim of this study was to identify the potential serum biomarkers of
      babesiosis using proteomic techniques in order to increase our understanding
      about disease pathogenesis. RESULTS: Serum samples were collected from 25 dogs of
      various breeds and sex with naturally occurring babesiosis caused by B. canis
      canis. Blood was collected on the day of admission (day 0), and subsequently on
      the 1st and 6th day of treatment. Two-dimensional electrophoresis (2DE) of pooled
      serum samples of dogs with naturally occurring babesiosis (day 0, day 1 and day
      6) and healthy dogs were run in triplicate. 2DE image analysis showed 64
      differentially expressed spots with p <= 0.05 and 49 spots with fold change >=2.
      Six selected spots were excised manually and subjected to trypsin digest prior to
      identification by electrospray ionisation mass spectrometry on an Amazon ion trap
      tandem mass spectrometry (MS/MS). Mass spectrometry data was processed using Data
      Analysis software and the automated Matrix Science Mascot Daemon server. Protein
      identifications were assigned using the Mascot search engine to interrogate
      protein sequences in the NCBI Genbank database. A number of differentially
      expressed serum proteins involved in inflammation mediated acute phase response,
      complement and coagulation cascades, apolipoproteins and vitamin D metabolism
      pathway were identified in dogs with babesiosis. CONCLUSIONS: Our findings
      confirmed two dominant pathogenic mechanisms of babesiosis, haemolysis and acute
      phase response. These results may provide possible serum biomarker candidates for
      clinical monitoring of babesiosis and this study could serve as the basis for
      further proteomic investigations in canine babesiosis.

PMID- 24885809
TI  - Differential regulation of the alpha-globin locus by Kruppel-like Factor 3 in
      erythroid and non-erythroid cells.
AB  - BACKGROUND: Kruppel-like Factor 3 (KLF3) is a broadly expressed zinc-finger
      transcriptional repressor with diverse biological roles. During erythropoiesis,
      KLF3 acts as a feedback repressor of a set of genes that are activated by Kruppel
      like Factor 1 (KLF1). Noting that KLF1 binds alpha-globin gene regulatory
      sequences during erythroid maturation, we sought to determine whether KLF3 also
      interacts with the alpha-globin locus to regulate transcription. RESULTS: We
      found that expression of a human transgenic alpha-globin reporter gene is
      markedly up-regulated in fetal and adult erythroid cells of Klf3-/- mice.
      Inspection of the mouse and human alpha-globin promoters revealed a number of
      canonical KLF-binding sites, and indeed, KLF3 was shown to bind to these regions
      both in vitro and in vivo. Despite these observations, we did not detect an
      increase in endogenous murine alpha-globin expression in Klf3-/- erythroid
      tissue. However, examination of murine embryonic fibroblasts lacking KLF3
      revealed significant de-repression of alpha-globin gene expression. This suggests
      that KLF3 may contribute to the silencing of the alpha-globin locus in non
      erythroid tissue. Moreover, ChIP-Seq analysis of murine fibroblasts demonstrated
      that across the locus, KLF3 does not occupy the promoter regions of the alpha
      globin genes in these cells, but rather, binds to upstream, DNase hypersensitive
      regulatory regions. CONCLUSIONS: These findings reveal that the occupancy profile
      of KLF3 at the alpha-globin locus differs in erythroid and non-erythroid cells.
      In erythroid cells, KLF3 primarily binds to the promoters of the adult alpha
      globin genes, but appears dispensable for normal transcriptional regulation. In
      non-erythroid cells, KLF3 distinctly binds to the HS-12 and HS-26 elements and
      plays a non-redundant, albeit modest, role in the silencing of alpha-globin
      expression.

PMID- 24885810
TI  - Influence of light-curing mode on the cytotoxicity of resin-based surface
      sealants.
AB  - BACKGROUND: Surface sealants have been successfully used in the prevention of
      erosive tooth wear. However, when multiple tooth surfaces should be sealed, the
      light-curing procedure is very time-consuming. Therefore, the aim of this study
      was to investigate whether reduced light-curing time (while maintaining similar
      energy density) has an influence on resin-based surface sealant cytotoxicity.
      METHODS: Bovine dentine discs were treated as follows: group 1: untreated, groups
      2-5: Seal&Protect and groups 6-9: experimental sealer. Groups 2 and 6 were light
      cured (VALO LED light-curing device) for 40 s (1000 mW/cm2), groups 3 and 7 for
      10 s (1000 mW/cm2), groups 4 and 8 for 7 s (1400 mW/cm2) and groups 5 and 9 for 3
      s (3200 mW/cm2). Later, materials were extracted in culture medium for 24 h, and
      released lactate dehydrogenase (LDH) activity as a measure of cytotoxicity was
      determined photometrically after cells (dental pulp cells and gingival
      fibroblasts) were exposed to the extracts for 24 h. Three independent
      experiments, for both sample preparation and cytotoxicity testing, were
      performed. RESULTS: Overall, lowest cytotoxicity was observed for the unsealed
      control group. No significant influence of light-curing settings on the
      cytotoxicity was observed (p = 0.537 and 0.838 for pulp cells and gingival
      fibroblasts, respectively). No significant difference in the cytotoxicity of the
      two sealants was observed after light-curing with same light-curing settings
      (group 2 vs. 6, 3 vs. 7, 4 vs. 8 and 5 vs. 9: p > 0.05, respectively).
      CONCLUSIONS: Shortening the light-curing time, while maintaining constant energy
      density, resulted in no higher cytotoxicity of the investigated sealants.

PMID- 24885811
TI  - Are weekend inpatient rehabilitation services value for money? An economic
      evaluation alongside a randomized controlled trial with a 30 day follow up.
AB  - BACKGROUND: Providing additional Saturday rehabilitation can improve functional
      independence and health related quality of life at discharge and it may reduce
      patient length of stay, yet the economic implications are not known. The aim of
      this study was to determine from a health service perspective if the provision of
      rehabilitation to inpatients on a Saturday in addition to Monday to Friday was
      cost effective compared to Monday to Friday rehabilitation alone. METHODS: Cost
      utility and cost effectiveness analyses were undertaken alongside a multi-center,
      single-blind randomized controlled trial with a 30-day follow up after discharge.
      Participants were adults admitted for inpatient rehabilitation in two publicly
      funded metropolitan rehabilitation facilities. The control group received usual
      care rehabilitation services from Monday to Friday and the intervention group
      received usual care plus an additional rehabilitation service on Saturday.
      Incremental cost utility ratio was reported as cost per quality adjusted life
      year (QALY) gained and an incremental cost effectiveness ratio (ICER) was
      reported as cost for a minimal clinically important difference (MCID) in
      functional independence. RESULTS: 996 patients (mean age 74 (standard deviation
      13) years) were randomly assigned to the intervention (n = 496) or the control
      group (n = 500). Mean difference in cost of AUD$1,673 (95% confidence interval
      (CI) -271 to 3,618) was a saving in favor of the intervention group. The
      incremental cost utility ratio found a saving of AUD$41,825 (95% CI -2,817 to
      74,620) per QALY gained for the intervention group. The ICER found a saving of
      AUD$16,003 (95% CI -3,074 to 87,361) in achieving a MCID in functional
      independence for the intervention group. If the willingness to pay per QALY
      gained or for a MCID in functional independence was zero dollars the probability
      of the intervention being cost effective was 96% and 95%, respectively. A
      sensitivity analysis removing Saturday penalty rates did not significantly alter
      the outcome. CONCLUSIONS: From a health service perspective, the provision of
      rehabilitation to inpatients on a Saturday in addition to Monday to Friday,
      compared to Monday to Friday rehabilitation alone, is likely to be cost saving
      per QALY gained and for a MCID in functional independence. TRIAL REGISTRATION:
      Australian and New Zealand Clinical Trials Registry November 2009
      ACTRN12609000973213.

PMID- 24885812
TI  - Developing a good practice model to evaluate the effectiveness of comprehensive
      primary health care in local communities.
AB  - BACKGROUND: This paper describes the development of a model of Comprehensive
      Primary Health Care (CPHC) applicable to the Australian context. CPHC holds
      promise as an effective model of health system organization able to improve
      population health and increase health equity. However, there is little literature
      that describes and evaluates CPHC as a whole, with most evaluation focusing on
      specific programs. The lack of a consensus on what constitutes CPHC, and the
      complex and context-sensitive nature of CPHC are all barriers to evaluation.
      METHODS: The research was undertaken in partnership with six Australian primary
      health care services: four state government funded and managed services, one
      sexual health non-government organization, and one Aboriginal community
      controlled health service. A draft model was crafted combining program logic and
      theory-based approaches, drawing on relevant literature, 68 interviews with
      primary health care service staff, and researcher experience. The model was then
      refined through an iterative process involving two to three workshops at each of
      the six participating primary health care services, engaging health service
      staff, regional health executives and central health department staff. RESULTS:
      The resultant Southgate Model of CPHC in Australia model articulates the theory
      of change of how and why CPHC service components and activities, based on the
      theory, evidence and values which underpin a CPHC approach, are likely to lead to
      individual and population health outcomes and increased health equity. The model
      captures the importance of context, the mechanisms of CPHC, and the space for
      action services have to work within. The process of development engendered and
      supported collaborative relationships between researchers and stakeholders and
      the product provided a description of CPHC as a whole and a framework for
      evaluation. The model was endorsed at a research symposium involving
      investigators, service staff, and key stakeholders. CONCLUSIONS: The development
      of a theory-based program logic model provided a framework for evaluation that
      allows the tracking of progress towards desired outcomes and exploration of the
      particular aspects of context and mechanisms that produce outcomes. This is
      important because there are no existing models which enable the evaluation of
      CPHC services in their entirety.

PMID- 24885813
TI  - Radical scavenging of white tea and its flavonoid constituents by electron
      paramagnetic resonance (EPR) spectroscopy.
AB  - White tea (WT) presents high levels of catechins, which are known to reduce
      oxidative stress. WT is the least processed tea, unfermented and prepared only
      from very young tea leaves. The subject of this paper is the use of the spin trap
      method and electron paramagnetic resonance (EPR) spectroscopy as the analytical
      tool to measure, for the first time, the radical scavenging activity of WT and
      its major catechin components, epicatechin (EC), epicatechin-3-gallate (ECG),
      epigallocatechin (EGC), and epigallocatechin-3-gallate (EGCG), against the
      methoxy radical, using ferulic acid as antioxidant pattern. The antioxidant
      activity has been measured by the decrease of the intensity of the spectral bands
      of the adduct DMPO-OCH3 in the EPR with the amount of antioxidant in the reactive
      mixture. Tea leaves and buds were extracted with waterless methanol. It has been
      proved that tea compounds with more antiradical activity against methoxy radical
      are those with the gallate group, EGCG and ECG. 

PMID- 24885814
TI  - Prognostic factors for recurrence-free and overall survival after adrenalectomy
      for metastatic carcinoma: a retrospective cohort pilot study.
AB  - BACKGROUND: The survival benefits of adrenalectomy (ADx) in the setting of
      metastatic cancer and prognostic factors for recurrence-free (RFS) and overall
      survival (OS) after adrenalectomy for metastatic carcinoma are still under
      debate. We evaluated the impact of clinicopathological variables on RFS and OS
      after ADx for metastatic carcinoma in patients with primary cancer. METHODS: A
      total of 32 patients undergoing ADx for metastatic cancer between 2004 and 2012
      at two tertiary medical centers. Metastases were regarded as synchronous (<6
      months) or metachronous (>=6 months) depending on the interval after primary
      surgery. Associations of perioperative clinicopathologic variables with RFS and
      OS were analyzed using Cox regression models. RESULTS: In total, 32 patients
      received ADx for metastatic primary tumors located in the lung (n = 11), colon (n
      = 4), liver (n = 5), stomach (n = 3), kidney (n = 4), pancreas (n = 2), glottis,
      esophagus, cervix, and ovary (n = 1 each). The overall recurrence rate after
      adrenalectomy was 62.5% (n = 20). By univariate analysis, C-reactive protein,
      inflammation-based prognosis score, and adrenalectomy for curative intent were
      associated with RFS and OS. Independent prognostic factors for shorter RFS were
      operative method (laparoscopy HR 4.68, 95% CI 1.61-13.61, p = 0.005) and
      inflammation-based prognostic score (HR 11.8, 95% CI 2.50-55.7, p = 0.002). For
      shorter OS, synchronous metastasis (HR 3.05, 95% CI 1.07-11.94, p = 0.048) and
      inflammation-based prognostic score (HR 6.65, 95% CI 1.25-35.23, p = 0.026) were
      identified as independent prognostic factors. CONCLUSIONS: Our pilot study
      suggests that synchronous disease and inflammation-based prognostic score are
      significant prognostic factors for survival and should be considered when
      performing ADx for metastatic diseases.

PMID- 24885815
TI  - Genetic variation in the CYP2B6 gene is related to circulating 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47) concentrations: an observational population
      based study.
AB  - BACKGROUND: Since human CYP2B6 has been identified as the major CYP enzyme
      involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and
      that human 2B6 is a highly polymorphic CYP, with known functional variants, we
      evaluated if circulating concentrations of a major brominated flame retardant,
      BDE-47, were related to genetic variation in the CYP2B6 gene in a population
      sample. METHODS: In the population-based Prospective Investigation of the
      Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25
      single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped.
      Circulating concentrations of BDE-47 were analyzed by high-resolution gas
      chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS).
      RESULTS: Several SNPs in the CYP2B6 gene were associated with circulating
      concentrations of BDE-47 (P = 10-4 to 10-9). The investigated SNPs came primarily
      from two haplotypes, although the correlation between the haplotypes was rather
      high. Conditional analyses adjusting for the SNP with the strongest association
      with the exposure (rs2014141) did not provide evidence for independent signals.
      CONCLUSION: Circulating concentrations of BDE-47 were related to genetic
      variation in the CYP2B6 gene in an elderly population.

PMID- 24885816
TI  - Perilla extract improves gastrointestinal discomfort in a randomized placebo
      controlled double blind human pilot study.
AB  - BACKGROUND: Gastrointestinal (GI) discomfort, e.g. bloating or rumbling, is a
      common symptom in otherwise healthy adults. Approximately 20% of the population,
      particularly women suffer from gastrointestinal discomfort and this affects
      quality of life. Recent studies discovered a link between the body and mind,
      called the gut-brain axis. Psychosocial factors, such as e.g. daily stress may
      cause altered gut physiology leading to ileum contractions and consequently
      gastrointestinal symptoms. In vitro and ex vivo studies clearly showed that a
      Perilla frutescens extract combines prokinetic, antispasmodic and anti
      inflammatory effects. The aim of the intervention was to investigate the effects
      of the proprietary Perilla extract on GI discomfort in healthy subjects with
      gastrointestinal discomfort and reduced bowel movements in comparison to a
      placebo product. METHODS: The pilot study was performed according to a double
      blind, randomized, placebo-controlled parallel design. Fifty healthy subjects
      with gastrointestinal discomfort and reduced bowel movements, 30-70 years,
      documented their GI symptoms, stool frequency and consistency daily during a 2
      week run-in phase and a 4-week intervention phase with Perilla frutescens extract
      or placebo. GI symptoms were assessed on a 5-point scale daily and average scores
      over 14 days intervals were calculated. RESULTS: All GI symptoms were
      significantly improved over time by Perilla frutescens extract during the
      intervention phase (bloating: -0.44+/-0.56, p=0.0003; passage of gas: -0.30+/
      0.66, p=0.0264; GI rumbling: -0.55+/-0.87, p=0.0014; feeling of fullness: -0.36+/
      0.72, p=0.0152; abdominal discomfort: -0.54+/-0.75, p=0.004), whereas in the
      placebo group only abdominal discomfort was significantly improved (-0.31+/-0.55,
      p=0.0345). In the subgroup of women results were strengthened and a subscore out
      of bloating and abdominal discomfort was significantly improved against placebo
      (95%CI 0.003 to 0.77; p=0.048). CONCLUSION: The demonstrated effects of Perilla
      frutescens extract to improve GI complaints offer very promising results, taking
      into consideration the challenging set up of a nutritional human study with
      healthy subjects and in the area of digestive health, which is known for high
      placebo effects. TRIAL REGISTRATION NUMBER: NCT01931930 at ClinicalTrials.gov,
      Registration date 23rd August 2013.

PMID- 24885817
TI  - Competence of birth attendants at providing emergency obstetric care under
      India's JSY conditional cash transfer program for institutional delivery: an
      assessment using case vignettes in Madhya Pradesh province.
AB  - BACKGROUND: Access to emergency obstetric care by competent staff can reduce
      maternal mortality. India has launched the Janani Suraksha Yojana (JSY)
      conditional cash transfer program to promote institutional births. During
      implementation of the JSY, India witnessed a steep increase in the proportion of
      institutional deliveries-from 40% in 2004 to 73% in 2012. However, maternal
      mortality reduction follows a secular trend. Competent management of
      complications, when women deliver in facilities under the JSY, is essential for
      reduction in maternal mortality and therefore to a successful program outcome. We
      investigate, using clinical vignettes, whether birth attendants at institutions
      under the program are competent at providing appropriate care for obstetric
      complications. METHODS: A facility based cross-sectional study was conducted in
      three districts of Madhya Pradesh (MP) province. Written case vignettes for two
      obstetric complications, hemorrhage and eclampsia, were administered to 233 birth
      attendant nurses at 73 JSY facilities. Their competence at (a) initial
      assessment, (b) diagnosis, and (c) making decisions on appropriate first-line
      care for these complications was scored. RESULTS: The mean emergency obstetric
      care (EmOC) competence score was 5.4 (median = 5) on a total score of 20, and 75%
      of participants scored below 35% of the maximum score. The overall score,
      although poor, was marginally higher in respondents with Skilled Birth Attendant
      (SBA) training, those with general nursing and midwifery qualifications, those at
      higher facility levels, and those conducting >30 deliveries a month. In all, 14%
      of respondents were competent at assessment, 58% were competent at making a
      correct clinical diagnosis, and 20% were competent at providing first-line care.
      CONCLUSIONS: Birth attendants in the JSY facilities have low competence at EmOC
      provision. Hence, births in the JSY program cannot be considered to have access
      to competent EmOC. Urgent efforts are required to effectively increase the
      competence of birth attendants at managing obstetric complications in order to
      translate large gains in coverage of institutional delivery services under JSY
      into reductions in maternal mortality in Madhya Pradesh, India.

PMID- 24885818
TI  - Gastritis cystica profunda recurrence after surgical resection: 2-year follow-up.
AB  - BACKGROUND: Gastritis cystica profunda (GCP) is an uncommon disease characterized
      by multiple cystic gastric glands within the submucosa of the stomach. CASE
      DESCRIPTION: Here, we present a case of a 63-year-old man with intermittent
      epigastric discomfort in whom gastroscopy revealed multiple irregular elevated
      nodular lesions with smooth surfaces at the anterior of the antrum. Surgical
      resection of the nodular lesions was performed, and the diagnosis of gastritis
      cystica profunda (GCP) was confirmed by histological examination. Another
      elevated nodular lesion approximately 10 mm in diameter with an ulcer was found
      on the gastric side of the remnant stomach near the resection side from 6 to 24
      months after the surgical resection. Endoscopic ultrasonography (EUS) and
      repeated biopsies of the new elevated lesion were performed. Homogeneous,
      anechoic masses originating from the submucosa without gastric adenocarcinoma in
      histological examination showed GCP recurrence may occur. CONCLUSIONS: We report
      a case of GCP recurrence within 6 months after surgical resection. GCP should be
      considered in the differential diagnosis of elevated lesions in the stomach.

PMID- 24885819
TI  - Phage idiotype vaccination: first phase I/II clinical trial in patients with
      multiple myeloma.
AB  - BACKGROUND: Multiple myeloma is characterized by clonal expansion of B cells
      producing monoclonal immunoglobulins or fragments thereof, which can be detected
      in the serum and/or urine and are ideal target antigens for patient-specific
      immunotherapies. METHODS: Using phage particles as immunological carriers, we
      employed a novel chemically linked idiotype vaccine in a clinical phase I/II
      trial including 15 patients with advanced multiple myeloma. Vaccines composed of
      purified paraproteins linked to phage were manufactured successfully for each
      patient. Patients received six intradermal immunizations with phage idiotype
      vaccines in three different dose groups. RESULTS: Phage idiotype was well
      tolerated by all study participants. A subset of patients (80% in the middle dose
      group) displayed a clinical response indicated by decrease or stabilization of
      paraprotein levels. Patients exhibiting a clinical response to phage vaccines
      also raised idiotype-specific immunoglobulins. Induction of a cellular immune
      response was demonstrated by a cytotoxicity assay and delayed type
      hypersensitivity tests. CONCLUSION: We present a simple, time- and cost-efficient
      phage idiotype vaccination strategy, which represents a safe and feasible patient
      specific therapy for patients with advanced multiple myeloma and produced
      promising anti-tumor activity in a subset of patients.

PMID- 24885820
TI  - Staphylococcus aureus and repeat bacteremia in febrile patients as early signs of
      sternal wound infection after cardiac surgery.
AB  - BACKGROUND: Sternal wound infection is a devastating complication of
      cardiothoracic surgery that carries high postoperative morbidity and mortality
      rates. We explored whether our current program of extensive bacteriological
      examination including repeat blood cultures may contribute to the early diagnosis
      of sternal wound infection. METHODS: We retrospectively analyzed 112 patients who
      were subjected to our bacteriological examination protocol including within 90
      days after cardiothoracic surgery. Univariate and multivariate analyses were made
      in order to identify risk factors for sternal infection. RESULTS: The median
      patient age was 75 years, and 65 patients were male. In 35 cases (31.2%) the
      blood cultures showed the presence of bacterial infection with the following
      frequencies: Staphylococcus aureus, 18 cases; Coagulase-negative Staphylococcus,
      7 cases; other organisms, 10 cases. Eleven patients presented repeat bacteremia
      on at least 2 different occasions. Twenty patients (17.8%) presented sternal
      wound infections. There was no difference in operative mortality between the
      patients with and without sternal wound infection. Univariate and multivariate
      analyses demonstrated that bilateral mammary artery use (OR, 13.68, 95% CI, 1.09
      167.36, p = 0.043), positive blood culture for Staphylococcus aureus (OR, 19.51,
      95% CI, 4.46-104.33, p < 0.0001), repeat bacteremia (OR, 17.98, 95% CI, 2.51
      161.77, p = 0.004) were risk factors that were associated for sternal wound
      infection. CONCLUSION: Repeat blood cultures in febrile patients appear to be
      useful for the early detection of Staphylococcus aureus and repeat bacteremia,
      and these were associated with sternal wound infection. Bilateral internal
      mammary artery use was another risk factor of sternal wound infection in febrile
      patients. These factors may identify patients suitable for expeditious
      radiological examination and aggressive treatments.

PMID- 24885821
TI  - Electronic problem list documentation of chronic kidney disease and quality of
      care.
AB  - BACKGROUND: Chronic kidney disease (CKD) is increasingly common and under
      recognized in primary care clinics, leading to low rates of stage-appropriate
      monitoring and treatment. Our objective was to determine whether electronic
      problem list documentation of CKD is associated with monitoring and treatment.
      METHODS: This is a cross-sectional observational study of patients with stage 3
      or 4 CKD, defined as two past estimated glomerular filtration rates (eGFR) 15-60
      mL/min/1.73 m2 separated by 90 days and collected between 2007-2008. We examined
      the association of problem list documentation with: 1) serum eGFR monitoring
      test, 2) urine protein or albumin monitoring test, 3) an angiotensin converting
      enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) prescription, 4) mean
      systolic blood pressure (BP), and 5) BP control. RESULTS: Out of 3,149 patients
      with stage 3 or 4 CKD, only 16% of patients had CKD documented on the problem
      list. After adjustment for eGFR, gender, and race/ethnicity and after clustering
      by physician, problem list documentation of CKD was associated with serum eGFR
      testing (97% with problem list documentation vs. 94% without problem list
      documentation, p=0.02) and urine protein testing (47% with problem list
      documentation vs. 40% without problem list documentation, p=0.04). After
      adjustment, problem list documentation was not associated with ACE/ARB
      prescription, mean systolic BP, or BP control. CONCLUSIONS: Documentation of CKD
      on the electronic problem list is rare. Patients with CKD documentation have
      better stage-appropriate monitoring of the disease, but do not have higher rates
      of blood pressure treatment or better blood pressure control. Interventions aimed
      at increasing documentation of CKD on the problem list may improve stage
      appropriate monitoring, but may not improve clinical outcomes.

PMID- 24885822
TI  - Interaction of body mass index and hemoglobin concentration on blood pressure
      among pregnant women in Guangxi, China.
AB  - BACKGROUND: Body mass index (BMI) and hemoglobin (Hb) are positively associated
      with hypertensive disorders among pregnant women. The aim of this study was to
      estimate a potential interaction between high BMI and high Hb concentrations on
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) in pregnancy.
      METHODS: We recruited 4497 single-birth women aged 18-43 years who received
      routine antenatal care at three hospitals of Guigang, Guangxi, China, from
      December 2007 to January 2011. Of 4497 participants, 3472 women were in the first
      trimester, with following up, 2986 women and 2261 women were left in the second
      and third trimester, respectively. Clinical data were derived from medical
      records of each woman. We used multivariable linear regression, by trimesters of
      pregnancy, to evaluate the associations of high BMI and high Hb concentrations
      with SBP and DBP according to cross-sectional design. RESULTS: In multivariable
      analyses, BMI was positively associated with SBP throughout all trimesters, but
      the corresponding association for Hb concentrations only in the first trimester,
      whereas both BMI and Hb concentrations were positively associated with DBP in the
      first and third trimesters. After full adjustment for confounding, the average
      differences in SBP and DBP comparing women with high BMI and high Hb to those
      with non-high BMI and non-high Hb were 2.9 mmHg (95% CI: 0.8 to 5.0 mmHg) and 3.9
      mmHg (95% CI: 1.5 to 6.3 mmHg) in the first trimester, 2.6 mmHg (95% CI: 0.4 to
      4.8 mmHg) and 1.5 mmHg (95% CI: -1.3 to 4.3 mmHg) in the second trimester, and
      4.8 mmHg (95% CI: 2.3 to 7.4 mmHg) and 5.7 mmHg (95% CI: 3.2 to 8.3 mmHg) in the
      third trimester, respectively. With respect to the interaction, significant
      combined effects between high BMI and high Hb were confirmed on SBP (P = 0.02)
      and DBP (P = 0.004) in the third trimester, and the amount of interaction on SBP
      and DBP were 2.0 mmHg (95% CI: 0.1 to 3.9 mmHg) and 2.3 mmHg (95% CI: 0.4 to 4.3
      mmHg), respectively. CONCLUSION: Our findings suggest that high BMI and high Hb
      concentrations may have a synergistic effect on blood pressure in late stage of
      pregnancy.

PMID- 24885823
TI  - Evaluation of subcortical grey matter abnormalities in patients with MRI-negative
      cortical epilepsy determined through structural and tensor magnetic resonance
      imaging.
AB  - BACKGROUND: Although many studies have found abnormalities in subcortical grey
      matter (GM) in patients with temporal lobe epilepsy or generalised epilepsies,
      few studies have examined subcortical GM in focal neocortical seizures. Using
      structural and tensor magnetic resonance imaging (MRI), we evaluated subcortical
      GM from patients with extratemporal lobe epilepsy without visible lesion on MRI.
      Our aims were to determine whether there are structural abnormalities in these
      patients and to correlate the extent of any observed structural changes with
      clinical characteristics of disease in these patients. METHODS: Twenty-four
      people with epilepsy and 29 age-matched normal subjects were imaged with high
      resolution structural and diffusion tensor MR scans. The patients were
      characterised clinically by normal brain MRI scans and seizures that originated
      in the neocortex and evolved to secondarily generalised convulsions. We first
      used whole brain voxel-based morphometry (VBM) to detect density changes in
      subcortical GM. Volumetric data, values of mean diffusivity (MD) and fractional
      anisotropy (FA) for seven subcortical GM structures (hippocampus, caudate
      nucleus, putamen, globus pallidus, nucleus accumbens, thalamus and amygdala) were
      obtained using a model-based segmentation and registration tool. Differences in
      the volumes and diffusion parameters between patients and controls and
      correlations with the early onset and progression of epilepsy were estimated.
      RESULTS: Reduced volumes and altered diffusion parameters of subcortical GM were
      universally observed in patients in the subcortical regions studied. In the
      patient-control group comparison of VBM, the right putamen, bilateral nucleus
      accumbens and right caudate nucleus of epileptic patients exhibited a
      significantly decreased density Segregated volumetry and diffusion assessment of
      subcortical GM showed apparent atrophy of the left caudate nucleus, left amygdala
      and right putamen; reduced FA values for the bilateral nucleus accumbens; and
      elevated MD values for the left thalamus, right hippocampus and right globus
      pallidus A decreased volume of the nucleus accumbens consistently related to an
      early onset of disease. The duration of disease contributed to the shrinkage of
      the left thalamus. CONCLUSIONS: Patients with neocortical seizures and secondary
      generalisation had smaller volumes and microstructural anomalies in subcortical
      GM regions. Subcortical GM atrophy is relevant to the early onset and progression
      of epilepsy.

PMID- 24885824
TI  - Testing a multi-malaria-model ensemble against 30 years of data in the Kenyan
      highlands.
AB  - BACKGROUND: Multi-model ensembles could overcome challenges resulting from
      uncertainties in models' initial conditions, parameterization and structural
      imperfections. They could also quantify in a probabilistic way uncertainties in
      future climatic conditions and their impacts. METHODS: A four-malaria-model
      ensemble was implemented to assess the impact of long-term changes in climatic
      conditions on Plasmodium falciparum malaria morbidity observed in Kericho, in the
      highlands of Western Kenya, over the period 1979-2009. Input data included
      quality controlled temperature and rainfall records gathered at a nearby weather
      station over the historical periods 1979-2009 and 1980-2009, respectively.
      Simulations included models' sensitivities to changes in sets of parameters and
      analysis of non-linear changes in the mean duration of host's infectivity to
      vectors due to increased resistance to anti-malarial drugs. RESULTS: The ensemble
      explained from 32 to 38% of the variance of the observed P. falciparum malaria
      incidence. Obtained R2-values were above the results achieved with individual
      model simulation outputs. Up to 18.6% of the variance of malaria incidence could
      be attributed to the +0.19 to +0.25 degrees C per decade significant long-term
      linear trend in near-surface air temperatures. On top of this 18.6%, at least 6%
      of the variance of malaria incidence could be related to the increased resistance
      to anti-malarial drugs. Ensemble simulations also suggest that climatic
      conditions have likely been less favourable to malaria transmission in Kericho in
      recent years. CONCLUSIONS: Long-term changes in climatic conditions and non
      linear changes in the mean duration of host's infectivity are synergistically
      driving the increasing incidence of P. falciparum malaria in the Kenyan
      highlands. User-friendly, online-downloadable, open source mathematical tools,
      such as the one presented here, could improve decision-making processes of local
      and regional health authorities.

PMID- 24885825
TI  - Fei-Liu-Ping ointment inhibits lung cancer growth and invasion by suppressing
      tumor inflammatory microenvironment.
AB  - BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality
      worldwide. Conventional chemotherapy and radiotherapy are the primary therapeutic
      methods for lung cancer with the use of combination therapies gaining popularity.
      The frequency and duration of treatment, as well as, managing lung cancer by
      targeting multiple aspects of cancer biology is often limited by toxicity to the
      patient. There are many naturally occurring anticancer agents that have a high
      degree of efficacy and low toxicity, offering a viable and safe approach for the
      treatment of lung cancer. The herbs traditionally used in Chinese medicine for
      anticancer treatment offer great potential to enhance the efficacy of
      conventional therapy. In this study, we evaluated the synergistic effects of Fei
      Liu-Ping (FLP) ointment in treating lung cancer; a known anticancer Chinese
      herbal based formula. METHODS: In this study, A549 human lung carcinoma cell line
      and Lewis lung carcinoma xenograft mouse model were used. In addition, we
      utilized an in vitro co-culture system to simulate the tumor microenvironment in
      order to evaluate the molecular mechanisms of FLP treatment. RESULTS: FLP
      treatment significantly inhibited tumor growth in the Lewis lung xenograft by 40
      percent, compared to that of cyclophosphamide (CTX) of 62.02 percent. Moreover,
      combining FLP and CTX inhibited tumor growth by 83.23 percent. Upon evaluation,
      we found that FLP treatment reduced the concentration of serum pro-inflammatory
      cytokines IL-6, TNF-alpha, and IL-1beta. In addition, we also found an
      improvement in E-cadherin expression and inhibition of N-cadherin and MMP9. We
      found similar findings in vitro when we co-cultured A549 cells with macrophages.
      FLP treatment inhibited A549 cell growth, invasion and metastasis, in part,
      through the regulation of NF-kappaB and altering the expression of E-cadherin, N
      cadherin, MMP2 and MMP9. CONCLUSIONS: FLP exerts anti-inflammatory properties in
      the tumor microenvironment, which may contribute to its anticancer effects. FLP
      treatment may be a promising therapy for inflammation associated lung cancer
      treatment alone, or in combination with conventional therapies and may prevent
      lung cancer metastasis.

PMID- 24885826
TI  - A study of role expansion: a new GP role in cardiology care.
AB  - BACKGROUND: The National Health Service is reconfiguring health care services in
      order to meet the increasing challenge of providing care for people with long
      term conditions and to reduce the demand on specialised outpatient hospital
      services by enhancing primary care. A review of cardiology referrals to
      specialised care and the literature on referral management inspired the
      development of a new GP role in Cardiology. This new extended role was developed
      to enable GPs to diagnose and manage patients with mild to moderate heart failure
      or atrial fibrillation and to use a range of diagnostics effectively in primary
      care. This entailed GPs participating in a four-session short course with on
      going clinical supervision. The new role was piloted in a small number of GP
      practices in one county in England for four months. This study explores the
      impact of piloting the Extended Cardiology role on the GP's role, patients'
      experience, service delivery and quality. METHODS: A mixed methods approach was
      employed including semi-structured interviews with GPs, a patient experience
      survey, a quality review of case notes, and analysis on activity and referral
      data. RESULTS: The participating GPs perceived the extended GP role as a
      professional development opportunity that had the potential to reduce healthcare
      utilisation and costs, through a reduction in referrals, whilst meeting the
      patient's wishes for the provision of care closer to home. Patient experience of
      the new GP service was positive. The standard of clinical practice was judged
      acceptable. There was a fall in referrals during the study period. CONCLUSION:
      This new role in cardiology was broadly welcomed as a model of care by the
      participating GPs and by patients, because of the potential to improve the
      quality of care for patients in primary care and reduce costs. As this was a
      pilot study further development and continuing evaluation of the model is
      recommended.

PMID- 24885827
TI  - Improving the estimation of the death rate of infected cells from time course
      data during the acute phase of virus infections: application to acute HIV-1
      infection in a humanized mouse model.
AB  - BACKGROUND: Mathematical modeling of virus dynamics has provided quantitative
      insights into viral infections such as influenza, the simian immunodeficiency
      virus/human immunodeficiency virus, hepatitis B, and hepatitis C. Through
      modeling, we can estimate the half-life of infected cells, the exponential growth
      rate, and the basic reproduction number (R0). To calculate R0 from virus load
      data, the death rate of productively infected cells is required. This can be
      readily estimated from treatment data collected during the chronic phase, but is
      difficult to determine from acute infection data. Here, we propose two new models
      that can reliably estimate the average life span of infected cells from acute
      phase data, and apply both methods to experimental data from humanized mice
      infected with HIV-1. METHODS: Both new models, called as the reduced quasi-steady
      state (RQS) model and the piece-wise regression (PWR) model, are derived by
      simplification of a standard model for the acute-phase dynamics of target cells,
      viruses and infected cells. By having only a limited number of parameters, both
      models allow us to reliably estimate the death rate of productively infected
      cells. Simulated datasets with plausible parameter values are generated with the
      standard model to compare the performance of the new models with that of the
      major previous model (i.e., the simple exponential model). Finally, we fit models
      to time course data from HIV-1 infected humanized mice to estimate the several
      important parameters characterizing their acute infection. RESULTS AND
      CONCLUSIONS: The new models provided much better estimates than the previous
      model because they more precisely capture the de novo infection process. Both
      models describe the acute phase of HIV-1 infected humanized mice reasonably well,
      and we estimated an average death rate of infected cells of 0.61 and 0.61, an
      average exponential growth rate of 0.69 and 0.76, and an average basic
      reproduction number of 2.30 and 2.38 in the RQS model and the PWR model,
      respectively. These estimates are fairly close to those obtained in humans.

PMID- 24885828
TI  - The effects of an integrated care intervention for the frail elderly on informal
      caregivers: a quasi-experimental study.
AB  - BACKGROUND: This study explored the effects of an integrated care model aimed at
      the frail elderly on the perceived health, objective burden, subjective burden
      and quality of life of informal caregivers. METHODS: A quasi-experimental design
      with before/after measurement (with questionnaires) and a control group was used.
      The analysis encompassed within and between groups analyses and regression
      analyses with baseline measurements, control variables (gender, age, co-residence
      with care receiver, income, education, having a life partner, employment and the
      duration of caregiving) and the intervention as independent variables. RESULTS:
      The intervention significantly contributed to the reduction of subjective burden
      and significantly contributed to the increased likelihood that informal
      caregivers assumed household tasks. No effects were observed on perceived,
      health, time investment and quality of life. CONCLUSIONS: This study implies that
      integrated care models aimed at the frail elderly can benefit informal caregivers
      and that such interventions can be implemented without demanding additional time
      investments from informal caregivers. Recommendations for future interventions
      and research are provided. TRIAL REGISTRATION: Current Controlled Trials
      http://ISRCTN05748494. Registration date: 14/03/2013.

PMID- 24885829
TI  - Associations of hormone replacement therapy and oral contraceptives with risk of
      colorectal cancer defined by clinicopathological factors, beta-catenin
      alterations, expression of cyclin D1, p53, and microsatellite-instability.
AB  - BACKGROUND: Postmenopausal hormone therapy (HRT) and oral contraceptive (OC) use
      have in several studies been reported to be associated with a decreased
      colorectal cancer (CRC) risk. However, data on the association between HRT and OC
      and risk of different clinicopathological and molecular subsets of CRC are
      lacking. The aim of this molecular pathological epidemiology study was therefore
      to evaluate the associations between HRT and OC use and risk of specific CRC
      subgroups, overall and by tumour site. METHOD: In the population-based
      prospective cohort study Mamo Diet and Cancer, including 17035 women, 304 cases
      of CRC were diagnosed up until 31 December 2008. Immunohistochemical expression
      of beta-catenin, cyclin D1, p53 and MSI-screening status had previously been
      assessed in tissue microarrays with tumours from 280 cases. HRT was assessed as
      current use of combined HRT (CHRT) or unopposed oestrogen (ERT), and analysed
      among 12583 peri-and postmenopausal women. OC use was assessed as ever vs never
      use among all women in the cohort. A multivariate Cox regression model was
      applied to determine hazard ratios for risk of CRC, overall and according to
      molecular subgroups, in relation to HRT and OC use. RESULTS: There was no
      significantly reduced risk of CRC by CHRT or ERT use, however a reduced risk of T
      stage 1-2 tumours was seen among CHRT users (HR: 0.24; 95% CI: 0.09
      0.77).Analysis stratified by tumour location revealed a reduced overall risk of
      rectal, but not colon, cancer among CHRT and ERT users, including T stage 1-2,
      lymph node negative, distant metastasis-free, cyclin D1 - and p53 negative
      tumours.In unadjusted analysis, OC use was significantly associated with a
      reduced overall risk of CRC (HR: 0.56; 95% CI: 0.44-0.71), but this significance
      was not retained in adjusted analysis (HR: 1.05: 95% CI: 0.80-1.37). A similar
      risk reduction was seen for the majority of clinicopathological and molecular
      subgroups. CONCLUSION: Our findings provide information on the relationship
      between use of HRT and OC and risk of clinicopathological and molecular subsets
      of CRC.

PMID- 24885830
TI  - Computational approaches for isoform detection and estimation: good and bad news.
AB  - BACKGROUND: The main goal of the whole transcriptome analysis is to correctly
      identify all expressed transcripts within a specific cell/tissue--at a particular
      stage and condition--to determine their structures and to measure their
      abundances. RNA-seq data promise to allow identification and quantification of
      transcriptome at unprecedented level of resolution, accuracy and low cost.
      Several computational methods have been proposed to achieve such purposes.
      However, it is still not clear which promises are already met and which
      challenges are still open and require further methodological developments.
      RESULTS: We carried out a simulation study to assess the performance of 5 widely
      used tools, such as: CEM, Cufflinks, iReckon, RSEM, and SLIDE. All of them have
      been used with default parameters. In particular, we considered the effect of the
      following three different scenarios: the availability of complete annotation,
      incomplete annotation, and no annotation at all. Moreover, comparisons were
      carried out using the methods in three different modes of action. In the first
      mode, the methods were forced to only deal with those isoforms that are present
      in the annotation; in the second mode, they were allowed to detect novel isoforms
      using the annotation as guide; in the third mode, they were operating in fully
      data driven way (although with the support of the alignment on the reference
      genome). In the latter modality, precision and recall are quite poor. On the
      contrary, results are better with the support of the annotation, even though it
      is not complete. Finally, abundance estimation error often shows a very skewed
      distribution. The performance strongly depends on the true real abundance of the
      isoforms. Lowly (and sometimes also moderately) expressed isoforms are poorly
      detected and estimated. In particular, lowly expressed isoforms are identified
      mainly if they are provided in the original annotation as potential isoforms.
      CONCLUSIONS: Both detection and quantification of all isoforms from RNA-seq data
      are still hard problems and they are affected by many factors. Overall, the
      performance significantly changes since it depends on the modes of action and on
      the type of available annotation. Results obtained using complete or partial
      annotation are able to detect most of the expressed isoforms, even though the
      number of false positives is often high. Fully data driven approaches require
      more attention, at least for complex eucaryotic genomes. Improvements are
      desirable especially for isoform quantification and for isoform detection with
      low abundance.

PMID- 24885831
TI  - Association between intraarticular cytokine levels and clinical parameters of
      osteochondritis dissecans in the ankle.
AB  - BACKGROUND: Reliable data about in vivo regulation of cytokines in
      osteochondritis dissecans (OCD) of the ankle are still missing. Disease-specific
      regulation patterns were hypothesized. METHODS: 28 patients with a mean age of
      30.7 +/- 14.8 years undergoing an arthroscopy of the ankle because of OCD were
      prospectively included in a clinical trial. Lavage fluids were analyzed by ELISA
      for levels of aggrecan, BMP-2, BMP-7, IGF-1, IGF-1R, bFGF, endoglin, MMP-13, and
      IL-1beta. Additionally, clinical parameters and scores (FFI, CFSS, AOFAS) were
      evaluated and supplemented by the Kellgren Lawrence Score (KLS) for conventional
      X-rays and the Ankle Osteoarthritis Scoring System (AOSS) for MRI. RESULTS:
      Grading of OCD lesions statistically significant increased with age and was
      higher in case of previously performed operations (p<0.03). A worse clinical
      function reflected by low AOFAS and CFSS scores or high FFI was associated with
      high grading of cartilage damage or OCD (p<0.03). Similarly, high radiological
      scores (KLS and AOSS) indicating progress of OA positively correlated with
      grading of cartilage damage and OCD. The concordance between the MRI and
      arthroscopic classification was overall moderate (kappa=0.52). Biochemically,
      only IGF/IGF-1R levels were consistently negatively associated with OCD grading,
      ICRS score, FFI and KLS (p<0.05). Correlation data is supported by post hoc
      statistics. CONCLUSIONS: Radiological and clinical parameters in association with
      synovial IGF-1/IGF-1R levels indicated an increasing joint degeneration with
      rising OCD stage. TRIAL REGISTRATION: German Clinical Trials Register
      DRKS00000365, 11/03/2008.

PMID- 24885832
TI  - Transcriptomic analysis of differential host gene expression upon uptake of
      symbionts: a case study with Symbiodinium and the major bioeroding sponge Cliona
      varians.
AB  - BACKGROUND: We have a limited understanding of genomic interactions that occur
      among partners for many symbioses. One of the most important symbioses in
      tropical reef habitats involves Symbiodinium. Most work examining Symbiodinium
      host interactions involves cnidarian partners. To fully and broadly understand
      the conditions that permit Symbiodinium to procure intracellular residency, we
      must explore hosts from different taxa to help uncover universal cellular and
      genetic strategies for invading and persisting in host cells. Here, we present
      data from gene expression analyses involving the bioeroding sponge Cliona varians
      that harbors Clade G Symbiodinium. RESULTS: Patterns of differential gene
      expression from distinct symbiont states ("normal", "reinfected", and
      "aposymbiotic") of the sponge host are presented based on two comparative
      approaches (transcriptome sequencing and suppressive subtractive hybridization
      (SSH)). Transcriptomic profiles were different when reinfected tissue was
      compared to normal and aposymbiotic tissue. We characterized a set of 40 genes
      drawn from a pool of differentially expressed genes in "reinfected" tissue
      compared to "aposymbiotic" tissue via SSH. As proof of concept, we determined
      whether some of the differentially expressed genes identified above could be
      monitored in sponges grown under ecologically realistic field conditions. We
      allowed aposymbiotic sponge tissue to become re-populated by natural pools of
      Symbiodinium in shallow water flats in the Florida Keys, and we analyzed gene
      expression profiles for two genes found to be increased in expression in
      "reinfected" tissue in both the transcriptome and via SSH. These experiments
      highlighted the experimental tractability of C. varians to explore with precision
      the genetic events that occur upon establishment of the symbiosis. We briefly
      discuss lab- and field-based experimental approaches that promise to offer
      insights into the co-opted genetic networks that may modulate uptake and
      regulation of Symbiondinium populations in hospite. CONCLUSIONS: This work
      provides a sponge transcriptome, and a database of putative genes and genetic
      pathways that may be involved in Symbiodinium interactions. The relative patterns
      of gene expression observed in these experiments will need to be evaluated on a
      gene-by-gene basis in controlled and natural re-infection experiments. We argue
      that sponges offer particularly useful characteristics for discerning essential
      dimensions of the Symbiodinium niche.

PMID- 24885833
TI  - Two single group, prospective, baseline-controlled feeding studies in infants and
      children with chronic diarrhea fed a hypoallergenic free amino acid-based
      formula.
AB  - BACKGROUND: Infants and children with chronic diarrhea (CD) often require
      specialized foods or parenteral nutrition (PN) to achieve adequate nutrient
      intakes to support growth and development. We assessed the efficacy of an amino
      acid-based formula (AAF) in supporting growth and improving symptoms in infants
      and children with CD from multiple etiologies. METHODS: Two studies were
      conducted: CD study in children (CD-C) and CD study in infants (CD-I). Each was a
      single group, baseline-controlled study in which each subject served as his/her
      own control. At enrollment, all subjects had CD lasting > 2 weeks and had >= 4
      stools/day. Subjects were fed an AAF for 80 days starting at SD5, and were
      assessed at SD 28 and 84. RESULTS CD-C: 18 of 19 subjects completed the study. At
      enrollment, the mean age was 5.6 +/- 0.7 years, the most common diagnosis was
      short bowel syndrome (SBS) (n = 13), and 5 subjects with SBS were on PN. Subjects
      achieved significant increases in weight-for-age z-scores (p = 0.026). Over 50%
      of subjects achieved improvements in clinical outcomes targeted most frequently
      by their physicians. Of the five subjects on PN at enrollment, four had
      substantial weight gain and four had their PN requirements decreased. CD-I: 22 of
      27 subjects completed the study. At enrollment, the mean age was 3.3 +/- 0.3
      months, the most common diagnosis was food allergy (n = 20), and no subjects were
      on PN. Subjects achieved significant increases in weight-for-age z-scores (p =
      0.0023), significant decreases in the number of stools/day (p = 0.0012), and
      improvements in stool consistency (p = 0.0024). Over 80% of subjects achieved
      improvements in the clinical outcomes targeted most frequently by their
      physicians. CONCLUSIONS: Infants and children with CD fed an AAF for three months
      displayed significant improvements in weight-for-age z-scores and clinical
      symptoms. Children dependent on PN also grew well and four of five decreased
      their dependence on PN. TRIAL REGISTRATION: Both trials were registered on
      ClinTrials.gov (CD-C, NCT01812629; CD-I, NCT01820494).

PMID- 24885834
TI  - Medical talc pleurodesis: which patient with cancer benefits least?
AB  - BACKGROUND AND OBJECTIVE: Successful talc pleurodesis (TP) for malignant pleural
      effusion (MPE) gives symptom relief, but may be too exhaustive in cases with poor
      performance status. The selection of eligible patients is therefore a challenging
      task. The study was undertaken to evaluate frequency of successful TPs, side
      effects, complications, performance status, hospitalization time, remaining time
      alive, and the responsible physician's prediction of a successful TP judged by
      radiologic findings prior to TP. METHODS: Side effects of TPs performed during a
      1-year period were consecutively recorded and the TP outcomes were
      retrospectively evaluated 6 years later. RESULTS: TP success rate was 56% and 79%
      among best support of care subjects (BSC; n=10) and subjects eligible for cancer
      therapy (non-BSC; n=19), respectively, while side effects did not differ.
      Performance status was poorer and survival shorter among BSC subjects. Time spent
      in hospital of the remaining time alive for BSC and non-BSC subjects was 42%+/
      27% and 4%+/-4%, respectively. Poor performance status of subjects with lung
      cancer correlated with short survival time, which in turn correlated with many
      days at hospital for TP. The physician's prediction of a successful TP was
      correct in 50% of all cases. CONCLUSIONS: Performance status of BSC subjects are
      probably too poor for TP and these subjects have to spend too much time at
      hospital during the procedure. The responsible physician is able to correctly
      predict a successful TP outcome in only every second case, supporting the need of
      additional predictive analysis.

PMID- 24885845
TI  - Polypoid nodular histiocytic hyperplasia associated with endometrioid
      adenocarcinoma of the endometrium: report of a case.
AB  - A 45 year old woman underwent Laparoscopy-assisted total hysterectomy with
      staging procedure following a diagnosis of endometrial endometrioid
      adenocarcinoma on her endometrial biopsy. The hysterectomy specimen showed a FIGO
      I stage 1a, endometrioid carcinoma. A separate polypoid lesion in the
      endometrium, distinct from the carcinoma, was also identified. Microscopically
      the polypoid lesion was "nodular histiocytic hyperplasia". The H&E,
      immunohistochemical staining findings and the differential diagnoses are
      discussed in this report. Although description of similar lesions is available in
      the literature, the current lesion is unique as it is identified in a
      hysterectomy specimen in its entirety and its association with an endometrial
      endometrioid carcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can
      be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060511915121922.

PMID- 24885844
TI  - Manage at work: a randomized, controlled trial of a self-management group
      intervention to overcome workplace challenges associated with chronic physical
      health conditions.
AB  - BACKGROUND: The percentage of older and chronically ill workers is increasing
      rapidly in the US and in many other countries, but few interventions are
      available to help employees overcome the workplace challenges of chronic pain and
      other physical health conditions. While most workers are eligible for job
      accommodation and disability compensation benefits, other workplace strategies
      might improve individual-level coping and problem solving to prevent work
      disability. In this study, we hypothesize that an employer-sponsored group
      intervention program employing self-management principles may improve worker
      engagement and reduce functional limitation associated with chronic disorders.
      METHODS: In a randomized controlled trial (RCT), workers participating in an
      employer-sponsored self-management group intervention will be compared with a no
      treatment (wait list) control condition. Volunteer employees (n = 300) will be
      recruited from five participating employers and randomly assigned to intervention
      or control. Participants in the intervention arm will attend facilitated group
      workshop sessions at work (10 hours total) to explore methods for improving
      comfort, adjusting work habits, communicating needs effectively, applying
      systematic problem solving, and dealing with negative thoughts and emotions about
      work. Work engagement and work limitation are the principal outcomes. Secondary
      outcomes include fatigue, job satisfaction, self-efficacy, turnover intention,
      sickness absence, and health care utilization. Measurements will be taken at
      baseline, 6-, and 12-month follow-up. A process evaluation will be performed
      alongside the randomized trial. DISCUSSION: This study will be most relevant for
      organizations and occupational settings where some degree of job flexibility,
      leeway, and decision-making autonomy can be afforded to affected workers. The
      study design will provide initial assessment of a novel workplace approach and to
      understand factors affecting its feasibility and effectiveness. TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT01978392 (Issued November 6, 2013).

PMID- 24885846
TI  - Executive function assessment and adult attention-deficit/hyperactivity disorder:
      tasks versus ratings on the Barkley deficits in executive functioning scale.
AB  - Adults with attention-deficit/hyperactivity disorder (ADHD) exhibit variable
      impairments on executive function (EF) tasks. Due to this variability, ratings of
      EF (rather than tasks) have been proposed as an alternative method that better
      captures symptom severity and impairment among adults with ADHD. However, few
      studies have jointly examined performance across multiple neuropsychological
      domains and EF ratings as predictors of severity and impairment among adults with
      ADHD. Adults (N = 273) ages 18-38 years (M = 22.6 years, 55.3% male, 62.2% with
      ADHD) completed a comprehensive diagnostic and neurocognitive assessment, which
      included self and informant ratings of ADHD symptom severity and EF and tasks of
      arousal/activation, response inhibition, set shifting, interference control, and
      working memory. Hierarchical linear regression models indicated that tasks of
      arousal/activation and response inhibition uniquely predicted ADHD symptom
      dimensions and related impairments. Over and above EF task performance, EF
      ratings of time management significantly predicted increased inattention (beta =
      .209, p < .001, DeltaR2 = 3.9%), whereas ratings of restraint predicted increased
      hyperactivity/impulsivity (beta = .259, p < .001, DeltaR2 = 6.4%). Furthermore,
      EF ratings of time management, restraint, and emotion regulation incrementally
      accounted for variance in relationship, professional, and daily living
      impairments over and above EF task performance (DeltaR2 range = 1.7-7.7%).
      Results may help refine neurobiological theories and assessment of adult ADHD.

PMID- 24885847
TI  - Examining the factor structure and etiology of prosociality.
AB  - Prosociality is one construct included in the developmental propensity model
      proposed by Lahey and Waldman (2003, 2005) to explain the development of conduct
      problems in childhood and adolescence. Findings from previous literature on 2
      facets of prosociality, dispositional sympathy and respect for rules, suggest
      that both may have genetic and nonshared environmental influences, but only the
      latter may have shared environmental influence. The goal of the current article
      was to explore the structure of the prosociality disposition from a measurement
      perspective as well as to examine the etiology of this construct. The sample
      consisted of 686 twin pairs ages 7 to 13. Parents rated their children's
      prosociality using the Child and Adolescent Dispositions Scale. The factor
      structure of the prosociality scale was examined using confirmatory factor
      analysis to compare a 1-factor model with a 2-factor model. Twin analyses were
      used to examine the proportion of variance associated with genetic and
      environmental effects on the latent factor(s) from the best fitting model.
      Results of the current study suggest that prosociality is a disposition that can
      be conceptualized as 2 related factors rather than a unitary dimension. These 2
      factors map onto the subscales of the prosociality dimension (dispositional
      sympathy and respect for rules). Both factors had significant genetic and
      nonshared environmental influences, but only respect for rules had significant
      shared environmental influences. Examining the dispositional sympathy and respect
      for rules facets of prosociality separately allowed for the discovery that shared
      environmental factors may have more impact on respect for rules than sympathy.

PMID- 24885848
TI  - Psychometrically improved, abbreviated versions of three classic measures of
      impulsivity and self-control.
AB  - Self-reported impulsivity confers risk factor for substance abuse. However, the
      psychometric properties of many self-report impulsivity measures have been
      questioned, thereby undermining the interpretability of study findings using
      these measures. To better understand these measurement limitations and to suggest
      a path to assessing self-reported impulsivity with greater psychometric
      stability, we conducted a comprehensive psychometric evaluation of the Barratt
      Impulsiveness Scale-11 (BIS-11), the Behavioral Inhibition and Activation Scales
      (BIS/BAS), and the Brief Self-Control Scale (BSCS) using data from 1,449
      individuals who participated in substance use research. For each measure, we
      evaluated (a) latent factor structure, (b) measurement invariance, (c) test
      criterion relationships between the measures, and (d) test-criterion relations
      with drinking and smoking outcomes. Notably, we could not replicate the
      originally published latent structure for the BIS, BIS/BAS, or BSCS or any
      previously published alternative factor structure (English language). Using
      exploratory and confirmatory factor analysis, we identified psychometrically
      improved, abbreviated versions of each measure: 8-item, 2-factor BIS-11 (root
      mean-square error of approximation [RMSEA] = .06, comparative fit index [CFI] =
      .95); 13-item, 4-factor BIS/BAS (RMSEA = .04, CFI = .96); and 7-item, 2-factor
      BSCS (RMSEA = .05, CFI = .96). These versions evidenced (a) stable, replicable
      factor structures, (b) scalar measurement invariance, ensuring our ability to
      make statistically interpretable comparisons across subgroups of interest (e.g.,
      sex, race, drinking/smoking status), and (c) test-criterion relationships with
      each other and with drinking/smoking. This study provides strong support for
      using these psychometrically improved impulsivity measures, which improve data
      quality directly through better scale properties and indirectly through reducing
      response burden.

PMID- 24885849
TI  - 1,3-propanediol production with Citrobacter werkmanii DSM17579: effect of a dhaD
      knock-out.
AB  - BACKGROUND: 1,3-propanediol (PDO) is a substantially industrial metabolite used
      in the polymer industry. Although several natural PDO production hosts exist,
      e.g. Klebsiella sp., Citrobacter sp. and Clostridium sp., the PDO yield on
      glycerol is insufficient for an economically viable bio-process. Enhancing this
      yield via strain improvement can be achieved by disconnecting the production and
      growth pathways. In the case of PDO formation, this approach results in a
      microorganism metabolizing glycerol strictly for PDO production, while
      catabolizing a co-substrate for growth and maintenance. We applied this strategy
      to improve the PDO production with Citrobacter werkmanii DSM17579. RESULTS:
      Genetic tools were developed and used to create Citrobacter werkmanii DSM17579
      ?dhaD in which dhaD, encoding for glycerol dehydrogenase, was deleted. Since this
      strain was unable to grow on glycerol anaerobically, both pathways were
      disconnected. The knock-out strain was perturbed with 13 different co-substrates
      for growth and maintenance. Glucose was the most promising, although a
      competition between NADH-consuming enzymes and 1,3-propanediol dehydrogenase
      emerged. CONCLUSION: Due to the deletion of dhaD in Citrobacter werkmanii
      DSM17579, the PDO production and growth pathway were split. As a consequence, the
      PDO yield on glycerol was improved 1,5 times, strengthening the idea that
      Citrobacter werkmanii DSM17579 could become an industrially interesting host for
      PDO production.

PMID- 24885850
TI  - Correlation between tuberculin skin test and IGRAs with risk factors for the
      spread of infection in close contacts with sputum smear positive in pulmonary
      tuberculosis.
AB  - BACKGROUND: The aim of the study was to assess the correlation between the
      tuberculin skin test (TST) and in vitro interferon-gamma released assays (IGRAs)
      with risk factors for the spread of infection in smear positive pulmonary
      tuberculosis (TB) contacts. METHODS: We recruited prospective contacts with smear
      positive pulmonary TB cases. We looked at human immunodeficiency virus (HIV)
      infection and other conditions of immunosuppression, presence of BCG vaccination
      and the degree of exposure to the index case. Patients underwent the TST, chest
      radiography, sputum analysis when necessary, and IGRA assays (QFN-G-IT and T
      SPOT.TB). Presence of cough, diagnostic delay (days between first symptoms and TB
      diagnostic), contact conditions: room size (square meters) and index of
      overcrowding (square meters per person) were investigated in the index case.
      RESULTS: 156 contacts (119 adults, 37 children) of 66 TB patients were enrolled,
      2.4 (1-14) contacts per TB case. The positivity of the TST did not correlate with
      the risk factors studied: presence of cough (p = 0.929); delayed diagnosis (p =
      0.244); room size (p = 0.462); overcrowding (p = 0.800). Both QFN-G-IT and T
      SPOT.TB, showed significant association with cough (p = 0.001, and p = 0.007) and
      room size (p = 0.020, and p = 0.023), respectively. CONCLUSIONS: Both IGRA
      associated better than TST with certain host-related risk factors involved in the
      transmission of disease, such as the presence of cough.

PMID- 24885851
TI  - Gender differences in suicide attempters: a retrospective study of precipitating
      factors for suicide attempts at a critical emergency unit in Japan.
AB  - BACKGROUND: There is a shortage of empirical data concerning precipitating
      factors for suicides in Japan. The purpose of the present study was to clarify
      gender differences of precipitating factors for suicide attempts in Japan.
      METHODS: The subjects were high-lethality suicide attempters who were admitted to
      the Nippon Medical School Hospital Critical Care Medical Center between March 1,
      2010 and March 31, 2012. Precipitating factors for suicide attempt, method of
      suicide attempt, psychiatric diagnoses and other sociodemographic data were
      collected from the patients' medical records retrospectively, and statistical
      analyses were performed for categorical variables of male/female. RESULTS: The
      total number of subjects was 193 (88 males and 105 females). The rate of subjects
      attempting suicide by poisonous gas was significantly higher in males while that
      of subjects attempting suicide by drug overdose was significantly higher in
      females. The rate of subjects diagnosed with "major depressive disorder, bipolar
      disorder" was significantly higher in males while that of subjects diagnosed with
      "personality disorders" or "dysthymic disorder" was significantly higher in
      females. Subjects with "health problems", "financial problems", "work problems",
      "debts (others)" or "unwanted transfer" were significantly more numerous among
      males; subjects with "family problems", "parent-child relations" or "loneliness"
      were significantly more frequently found among females. CONCLUSIONS: Mental
      disorders were the most common precipitating factor for suicide attempts
      regardless of gender. Significant gender differences were observed in psychiatric
      diagnoses, methods of suicide attempt and psychosocial problems. This indicates
      the necessity of suicide prevention measures corresponding to these gender
      differences.

PMID- 24885852
TI  - History and complexity in tick-host dynamics: discrepancies between 'real' and
      'visible' tick populations.
AB  - BACKGROUND: Numerical responses of ticks to changes in densities of their hosts
      can be complex and apparently unpredictable. Manipulations even of deterministic
      models can produce counter-intuitive results, including tick populations that
      either rise or fall under increasing host densities, depending on initial
      conditions. METHODS: In this paper I use an established simulation model to
      demonstrate a wide range of numerical responses to different scenarios of host
      changes, and to examine the basic mechanisms that drive them. RESULTS: The rate
      and direction of change of host densities affects the extent to which questing
      tick numbers reflect those of their hosts. Numerical responses differ profoundly
      between dynamic tick-host systems and those allowed to reach equilibrium.
      CONCLUSIONS: The key to understanding tick-host dynamics is to understand the
      difference between 'real' and 'visible' tick populations. An appreciation of the
      implications of this difference - and of the conditions that influence it - will
      benefit the effective interpretation of field data.

PMID- 24885853
TI  - Working and hypertension: gaps in employment not associated with increased risk
      in 13 European countries, a retrospective cohort study.
AB  - BACKGROUND: There is growing evidence to suggest unemployment has a role in the
      development and incidence of cardiovascular disease. This study explores the
      contribution of breaks in employment to the development of hypertension, a key
      risk factor for coronary heart disease. METHODS: We use data from the Survey of
      Health, Ageing, and Retirement in Europe to estimate the association between gaps
      in employment of 6 months or more ('Not Working', NW) and the incidence of
      hypertension in 9,985 individuals aged 50 or over across 13 European countries.
      Life history information including transitions in and out of employment was used
      to create a panel dataset where each visit represented one year of life between
      age 30 and incident hypertension or censoring (whichever came first). Pooled
      logistic models estimated the odds of hypertension according to the experience of
      not working, controlling for age at interview, age at each visit, gender,
      childhood socio-economic position, and country. RESULTS: We consistently found no
      association between NW and hypertension, irrespective of the metrics used in
      defining the exposure or model specification. CONCLUSION: There is the
      possibility of bias contributing to the null findings. However, given the
      relatively consistent evidence for an association between unemployment and
      cardiovascular outcomes in the literature, our results suggest there may be
      mechanisms - outside of hypertension - that have a comparatively greater
      contribution to this association.

PMID- 24885854
TI  - A method for increasing expressivity of Gene Ontology annotations using a
      compositional approach.
AB  - BACKGROUND: The Gene Ontology project integrates data about the function of gene
      products across a diverse range of organisms, allowing the transfer of knowledge
      from model organisms to humans, and enabling computational analyses for
      interpretation of high-throughput experimental and clinical data. The core data
      structure is the annotation, an association between a gene product and a term
      from one of the three ontologies comprising the GO. Historically, it has not been
      possible to provide additional information about the context of a GO term, such
      as the target gene or the location of a molecular function. This has limited the
      specificity of knowledge that can be expressed by GO annotations. RESULTS: The GO
      Consortium has introduced annotation extensions that enable manually curated GO
      annotations to capture additional contextual details. Extensions represent
      effector-target relationships such as localization dependencies, substrates of
      protein modifiers and regulation targets of signaling pathways and transcription
      factors as well as spatial and temporal aspects of processes such as cell or
      tissue type or developmental stage. We describe the content and structure of
      annotation extensions, provide examples, and summarize the current usage of
      annotation extensions. CONCLUSIONS: The additional contextual information
      captured by annotation extensions improves the utility of functional annotation
      by representing dependencies between annotations to terms in the different
      ontologies of GO, external ontologies, or an organism's gene products. These
      enhanced annotations can also support sophisticated queries and reasoning, and
      will provide curated, directional links between many gene products to support
      pathway and network reconstruction.

PMID- 24885855
TI  - Authorship ethics in global health research partnerships between researchers from
      low or middle income countries and high income countries.
AB  - BACKGROUND: Over the past two decades, the promotion of collaborative
      partnerships involving researchers from low and middle income countries with
      those from high income countries has been a major development in global health
      research. Ideally, these partnerships would lead to more equitable collaboration
      including the sharing of research responsibilities and rewards. While
      collaborative partnership initiatives have shown promise and attracted growing
      interest, there has been little scholarly debate regarding the fair distribution
      of authorship credit within these partnerships. DISCUSSION: In this paper, we
      identify four key authorship issues relevant to global health research and
      discuss their ethical and practical implications. First, we argue that authorship
      guidance may not adequately apply to global health research because it requires
      authors to write or substantially revise the manuscript. Since most journals of
      international reputation in global health are written in English, this would
      systematically and unjustly exclude non-English speaking researchers even if they
      have substantially contributed to the research project. Second, current guidance
      on authorship order does not address or mitigate unfair practices which can occur
      in global health research due to power differences between researchers from high
      and low-middle income countries. It also provides insufficient recognition of
      "technical tasks" such as local participant recruitment. Third, we consider the
      potential for real or perceived editorial bias in medical science journals in
      favour of prominent western researchers, and the risk of promoting misplaced
      credit and/or prestige authorship. Finally, we explore how diverse cultural
      practices and expectations regarding authorship may create conflict between
      researchers from low-middle and high income countries and contribute to unethical
      authorship practices. To effectively deal with these issues, we suggest: 1)
      undertaking further empirical and conceptual research regarding authorship in
      global health research; 2) raising awareness on authorship issues in global
      health research; and 3) developing specific standards of practice that reflect
      relevant considerations of authorship in global health research. SUMMARY: Through
      review of the bioethics and global health literatures, and examination of
      guidance documents on ethical authorship, we identified a set of issues regarding
      authorship in collaborative partnerships between researchers from low-middle
      income countries and high income countries. We propose several recommendations to
      address these concerns.

PMID- 24885856
TI  - Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting
      CD137 expression: novel potential treatment for COPD.
AB  - BACKGROUND: We have shown that chronic obstructive pulmonary disease (COPD) is
      associated with increased production of pro-inflammatory cytokines and the
      cytotoxic mediator, granzyme B by peripheral blood steroid resistant
      CD28nullCD137 + CD8+ T cells and granzyme B by NKT-like and NK cells. We
      hypothesized that we could target these pro-inflammatory/cytotoxic lymphocytes by
      inhibiting co-stimulation through CD137. METHODS: Isolated PBMC from patients
      with COPD and healthy controls were stimulated with phytohaemagglutinin (PHA) +/-
      blocking anti-CD137 +/- 10(-6) M methylprednislone (MP) (+/-stimulatory anti
      CD137 +/- control antibodies). Pro-inflammatory cytokine profiles and expression
      of granzyme B, by T, NKT-like CD28 +/- subsets and NK cells were determined using
      flow cytometry. RESULTS: There was a significant decrease in the percentage of T,
      NKT-like subsets and NK cells producing IFNgamma, TNFalpha and granzyme B in all
      subjects in the presence of anti-CD137 blocking antibody compared with PHA alone
      (eg, 60% decrease in CD8 + granzyme B + cells) or MP. Stimulatory anti-CD137 was
      associated with an increase in the percentage of pro-inflammatory/cytotoxic
      cells. The inhibitory effect of anti-CD137 on IFNgamma, TNFalpha and granzyme B
      production by CD28null cells was greater than by CD28+ cells. CONCLUSIONS:
      Blocking CD137 expression is associated with downregulation of IFNgamma, TNFalpha
      and granzyme B by CD8+ T and NKT-like and NK cells. Targeting CD137 may have
      novel therapeutic implications for patients with COPD.

PMID- 24885857
TI  - Which combination of MR imaging modalities is best for predicting recurrent
      glioblastoma? Study of diagnostic accuracy and reproducibility.
AB  - PURPOSE: To compare the added value of dynamic contrast material-enhanced ( CE
      contrast enhanced ) ( DCE dynamic CE ) magnetic resonance (MR) imaging with that
      of dynamic susceptibility CE contrast enhanced ( DSC dynamic susceptibility CE )
      MR imaging with the combination of CE contrast enhanced T1-weighted imaging and
      diffusion-weighted ( DW diffusion weighted ) imaging for predicting recurrent
      glioblastoma. MATERIALS AND METHODS: This retrospective study was approved by the
      institutional review board, with the requirement for informed patient consent
      waived. CE contrast enhanced T1-weighted images, DW diffusion weighted images,
      DSC dynamic susceptibility CE MR images, and DCE dynamic CE MR images in 169
      patients with pathologically or clinicoradiologically diagnosed recurrent
      glioblastoma (n = 87) or radiation necrosis (n = 82) were retrospectively
      reviewed. Histogram cutoffs of quantitative parametric values were calculated
      from DW diffusion weighted images, DSC dynamic susceptibility CE MR images, and
      DCE dynamic CE MR images. Area under the receiver operating characteristic curve
      ( Az area under the ROC curve ) and interreader agreement were assessed. RESULTS:
      For predicting recurrent glioblastoma, adding DCE dynamic CE MR imaging to the
      combination of CE contrast enhanced T1-weighted imaging and DW diffusion weighted
      imaging significantly improved Az area under the ROC curve from 0.84 to 0.96 for
      reader 1 and from 0.81 to 0.97 for reader 2, respectively. Adding DSC dynamic
      susceptibility CE MR imaging also significantly improved Az area under the ROC
      curve (0.95 for reader 1 and 0.93 for reader 2). However, there was no
      significant difference in Az between the combination of CE contrast enhanced T1
      weighted imaging, DW diffusion weighted imaging, and DSC dynamic susceptibility
      CE MR imaging and the combination of CE contrast enhanced T1-weighted imaging, DW
      diffusion weighted imaging, and DCE dynamic CE MR imaging for both readers. The
      interreader agreement was highest for the combination of CE contrast enhanced T1
      weighted imaging, DW diffusion weighted imaging, and DCE dynamic CE MR imaging
      (kappa = 0.78) and lowest for CE contrast enhanced T1-weighted imaging and DW
      diffusion weighted imaging (kappa = 0.65). CONCLUSION: Adding perfusion MR
      imaging to the combination of CE contrast enhanced T1-weighted imaging and DW
      diffusion weighted imaging significantly improves the prediction of recurrent
      glioblastoma; however, selection of perfusion MR method does not affect the
      diagnostic performance.

PMID- 24885859
TI  - Short-stem reconstruction for megaendoprostheses in case of an ultrashort
      proximal femur.
AB  - BACKGROUND: Tumors of the distal femur and diaphysis with proximal metaphyseal
      extension into the femur present a challenge for limb salvage. The conventional
      treatment consists of limb salvage with total femur replacement. This case study
      aims to present preliminary results and experience with short-stem
      reconstruction, focusing on the mechanical stability of the procedure. METHODS:
      Sixteen short stems were implanted in 15 patients. The patients' mean age was
      33,3 years (range 11-73). In 10 patients, the stem was used for distal femur
      reconstruction, in one patient for diaphyseal reconstruction, and in four for a
      stump lengthening procedure. All of the patients had a primary sarcoma in their
      history. The mean follow-up period was 37 months (range 5-95 months). The
      clinical and functional follow-up data were analyzed. RESULTS: Ten patients (67%)
      were still alive at the time of evaluation. Three complications associated with
      the stem were noted. In one case, there was aseptic loosening after 58 months; in
      another, aseptic loosening occurred because the diameter of the stem had
      initially been too small; and in one case, there was breakage of the fixation
      screw, without any clinical symptoms. The average Musculoskeletal Tumor Society
      score for all patients was 23 (range 9-28). The mean result for the distal femur
      replacement was 24 (range 22-28). None of the surviving patients with distal
      femur replacements needed any crutches or had a Trendelenburg limp. Both living
      patients who underwent a stump lengthening procedure were able to walk with an
      exoprosthesis. CONCLUSIONS: The short stem is a good solution that can prevent or
      delay proximal femur resection in patients with tumors extending into the
      proximal metaphyseal femur. Additional risks of proximal femur resection, such as
      dislocation, opening of another oncological compartment, Trendelenburg limp, and
      chondrolysis can be avoided.

PMID- 24885858
TI  - Expression of natriuretic peptide receptor-A in esophageal squamous cell
      carcinomas and the relationship with tumor invasion and migration.
AB  - BACKGROUND: The natriuretic peptide receptor-A (NPRA) has been investigated as a
      receptor of natriuretic peptides in the cardiovascular system. In this study,
      however, we analyze the expression status of NPRA and the relationship with tumor
      invasion in esophageal squamous cell carcinoma (ESCC) for the first time.
      METHODS: Western blots were used to examine the expression status of protein in
      human ESCC cell lines. Then, we used immunohistochemistry to detect the
      expression of NPRA in 45 ESCC specimens and 40 corresponding nontumor tissues.
      The clinical data were analyzed through statistical methods. Sh-RNA-NPRA was
      transfected into Eca109 cells to detect the relationship between NPRA and cell
      invasion through transwell assays. RESULTS: In esophageal squamous cells, the
      expression of NPRA was strongly detected in the cytoplasm, while undetectable or
      very weak in the nucleus. The positive rates of NPRA in cancer tissues are
      significantly higher than that in nontumor tissues (P<0.05). Clinicopathological
      analyses revealed that increased NPRA expression correlated with differentiation
      and TNM stage (P<0.05), while it showed no statistically significant association
      with age, gender, and lymph node metastasis. In analysis of prognosis, we found
      that highly.Transwell assays showed that NPRA promoted Eca109 cell migration and
      invasion in vitro and may be involved in MMP2 and MMP9 activation. CONCLUSIONS:
      NPRA protein is highly expressed in ESCC tissues and could promote Eca109 cell
      migration and invasion in vitro.

PMID- 24885860
TI  - Analysing the socioeconomic determinants of hypertension in South Africa: a
      structural equation modelling approach.
AB  - BACKGROUND: Epidemiological research has long observed a varying prevalence of
      hypertension across socioeconomic strata. However, patterns of association and
      underlying causal mechanisms are poorly understood in sub-Saharan Africa. Using
      education and income as indicators, we investigated the extent to which
      socioeconomic status is linked to blood pressure in the first wave of the
      National Income Dynamics Study--a South African longitudinal study of more than
      15,000 adults--and whether bio-behavioural risk factors mediate the association.
      METHODS: In a cross-sectional analysis, structural equation modelling was
      employed to estimate the effect of socioeconomic status on systolic and diastolic
      blood pressure and to assess the role of a set of bio-behavioural risk factors in
      explaining the observed relationships. RESULTS: After adjustment for age, race
      and antihypertensive treatment, higher education and income were independently
      associated with higher diastolic blood pressure in men. In women higher education
      predicted lower values of both diastolic and systolic blood pressure while higher
      income predicted lower systolic blood pressure. In both genders, body mass index
      was a strong mediator of an adverse indirect effect of socioeconomic status on
      blood pressure. Together with physical exercise, alcohol use, smoking and resting
      heart rate, body mass index therefore contributed substantially to mediation of
      the observed relationships in men. By contrast, in women unmeasured factors
      played a greater role. CONCLUSION: In countries undergoing epidemiological
      transition, effects of socioeconomic status on blood pressure may vary by gender.
      In women, factors other than those listed above may have substantial role in
      mediating the association and merit investigation.

PMID- 24885861
TI  - Parents' preferences for vaccinating daughters against human papillomavirus in
      the Netherlands: a discrete choice experiment.
AB  - BACKGROUND: To generate knowledge about potential improvements to human
      papillomavirus (HPV) vaccination information and organization strategies, we
      assessed how aspects of HPV vaccination are associated with parents' preferences
      for their daughters' uptake, and which trade-offs parents are willing to make
      between these aspects. METHODS: A discrete choice experiment (DCE) was conducted
      among parents with a daughter aged 10-12 years. Panel mixed logit regression
      models were used to determine parents' preferences for vaccination. Trade-offs
      were quantified between four vaccination programme aspects: degree of protection
      against cervical cancer, duration of protection, risk of serious side-effects,
      and age of vaccination. RESULTS: Total response rate was 302/983 (31%). All
      aspects influenced respondents' preferences for HPV vaccination (p < 0.05).
      Respondents preferred vaccination at age 14 years instead of at a younger age.
      Respondents were willing to trade-off 11% of the degree of protection to obtain
      life-time protection instead of 25 years. To obtain a vaccination with a risk of
      serious side-effects of 1/750,000 instead of 1/150,000, respondents were willing
      to trade-off 21%. CONCLUSIONS: Uptake may rise if the age ranges for free HPV
      vaccinations are broadened. Based on the trade-offs parents were willing to make,
      we conclude that uptake would increase if new evidence indicated outcomes are
      better than are currently understood, particularly for degree and duration of
      protection.

PMID- 24885862
TI  - A cross-sectional study of demographic, environmental and parental barriers to
      active school travel among children in the United States.
AB  - BACKGROUND: Promoting daily routine physical activities, such as active travel to
      school, may have important health implications. Practitioners and policy makers
      must understand the variety of factors that influence whether or not a child uses
      active school travel. Several reviews have identified both inhibitors and
      promoters of active school travel, but few studies have combined these putative
      characteristics in one analysis. The purpose of this study is to examine
      associations between elementary school children's active school travel and
      variables hypothesized as correlates (demographics, physical environment,
      perceived barriers and norms). METHODS: The current project uses the dataset from
      the National Evaluation of Walk to School (WTS) Project, which includes data from
      4th and 5th grade children and their parents from 18 schools across the US.
      Measures included monthly child report of mode of school travel during the
      previous week (n = 10,809) and perceived barriers and social norms around active
      school travel by parents (n = 1,007) and children (n = 1,219). Generalized linear
      mixed models (GLMM) with log-link functions were used to assess bivariate and
      multivariate associations between hypothesized correlates and frequency of active
      school travel, assuming random school effect and controlling for the distance to
      school. RESULTS: The final model showed that the most relevant significant
      predictors of active school travel were parent's perceived barriers, specifically
      child resistance (Estimate = -0.438, p < 0.0001) and safety and weather (Estimate
      = -0.0245, p < 0.001), as well as the school's percentage of Hispanic students
      (Estimate = 0.0059, p < 0.001), after adjusting for distance and including time
      within school cluster as a random effect. CONCLUSIONS: Parental concerns may be
      impacting children's use of active school travel, and therefore, future
      interventions to promote active school travel should more actively engage parents
      and address these concerns. Programs like the Walk to School program, which are
      organized by the schools and can engage community resources such as public safety
      officials, could help overcome many of these perceived barriers to active
      transport.

PMID- 24885863
TI  - Effects of established BMI-associated loci on obesity-related traits in a French
      representative population sample.
AB  - BACKGROUND: Genome-wide association studies have identified variants associated
      with obesity-related traits, such as the body mass index (BMI). We sought to
      determine how the combination of 31 validated, BMI-associated loci contributes to
      obesity- and diabetes-related traits in a French population sample. The MONA LISA
      Lille study (1578 participants, aged 35-74) constitutes a representative sample
      of the population living in Lille (northern France). Genetic variants were
      considered both individually and combined into a genetic predisposition score
      (GPS). RESULTS: Individually, 25 of 31 SNPs showed directionally consistent
      effects on BMI. Four loci (FTO, FANCL, MTIF3 and NUDT3) reached nominal
      significance (p <= 0.05) for their association with anthropometric traits. When
      considering the combined effect of the 31 SNPs, each additional risk allele of
      the GPS was significantly associated with an increment in the mean [95% CI] BMI
      of 0.13 [0.07-0.20] kg/m2 (p = 6.3x10-5) and a 3% increase in the risk of obesity
      (p = 0.047). The GPS explained 1% of the variance in the BMI. Furthermore, the
      GPS was associated with higher fasting glycaemia (p = 0.04), insulinaemia (p =
      0.008), HbA1c levels (p = 0.01) and HOMA-IR scores (p = 0.0003) and a greater
      risk of type 2 diabetes (OR [95% CI] = 1.06 [1.00-1.11], p = 0.03). However,
      these associations were no longer statistically significant after adjustment for
      BMI. CONCLUSION: Our results show that the GPS was associated with a higher BMI
      and an insulin-resistant state (mediated by BMI) in a population in northern
      France.

PMID- 24885864
TI  - Relationship between the area of isopters and Vigabatrin dosage during two years
      of observation.
AB  - BACKGROUND: The aim of the study was to evaluate the relationship between the
      area of isopters obtained using semi-automated kinetic perimetry (SKP) and
      Vigabatrin dosage in epilepsy patients with pretreatment baseline examination
      during 2-years of the follow-up. METHODS: 29 epilepsy patients were included into
      the study, but 15 individuals were excluded due to cognitive impairment,
      intracranial pathologies or eye diseases. Finally, 14 patients were examined with
      SKP before VGB treatment and after 6, 12, 18, and 24 months. Reaction time (RT)
      corrected areas of three isopters (III4e, I4e and I2e) were measured for each of
      five examinations and compared intra-individually during 2-years period.
      Additionally, six epilepsy patients on other antiepileptic drugs were examined
      five times with SKP as a control. RESULTS: There was a significant decrease of
      I2e, I4e and III4e isopters' area during the follow-up of two years. Correlation
      was found between the I2e isopter's area and both cumulative dose and mean daily
      dose of VGB. With increasing RT, there was decreasing of all isopters' area in
      patients receiving VGB. In epilepsy patients who were not receiving VGB, there
      were no significance differences in isopters' area during follow-up. CONCLUSION:
      There was attenuation of area of III4e, I4e and I2e isopters obtained with SKP
      during a period of 2 years. RT, the cumulative dose and the mean daily dose of
      VGB influenced isopters' area obtained with SKP.

PMID- 24885865
TI  - Survey and analysis of the current state of residency training in medical-school
      affiliated hospitals in China.
AB  - BACKGROUND: Since the global standards for postgraduate medical education (PGME)
      were published in January 2003, they have gained worldwide attention. The current
      state of residency training programs in medical-school-affiliated hospitals
      throughout China was assessed in this study. METHODS: Based on the
      internationally recognized global standards for PGME, residents undergoing
      residency training at that time and the relevant residency training instructors
      and management personnel from 15 medical-school-affiliated hospitals throughout
      China were recruited and surveyed regarding the current state of residency
      training programs. A total of 938 questionnaire surveys were distributed between
      June 30, 2006 and July 30, 2006; of 892 surveys collected, 841 were valid.
      RESULTS: For six items, the total proportions of "basically meets standards" and
      "completely meets standards" were <70% for the basic standards. These items were
      identified in the fields of "training settings and educational resources",
      "evaluation of training process", and "trainees". In all fields other than
      "continuous updates", the average scores of the western regions were
      significantly lower than those of the eastern regions for both the basic and
      target standards. Specifically, the average scores for the basic standards on as
      many as 25 of the 38 items in the nine fields were significantly lower in the
      western regions. There were significant differences in the basic standards scores
      on 13 of the 38 items among trainees, instructors, and managers. CONCLUSIONS: The
      residency training programs have achieved satisfactory outcomes in the hospitals
      affiliated with various medical schools in China. However, overall, the programs
      remain inadequate in certain areas. For the governments, organizations, and
      institutions responsible for PGME, such global standards for PGME are a very
      useful self-assessment tool and can help identify problems, promote reform, and
      ultimately standardize PGME.

PMID- 24885866
TI  - Prediction of future labour market outcome in a cohort of long-term sick-listed
      Danes.
AB  - BACKGROUND: Targeted interventions for the long-term sick-listed may prevent
      permanent exclusion from the labour force. We aimed to develop a prediction
      method for identifying high risk groups for continued or recurrent long-term
      sickness absence, unemployment, or disability among persons on long-term sick
      leave. METHODS: We obtained individual characteristics and follow-up data from
      the Danish Register of Sickness Absence Compensation Benefits and Social Transfer
      Payments (RSS) during 2004 to 2010 for 189,279 Danes who experienced a period of
      long-term sickness absence (4+ weeks). In a learning data set, statistical
      prediction methods were built using logistic regression and a discrete event
      simulation approach for a one year prediction horizon. Personalized risk profiles
      were obtained for five outcomes: employment, unemployment, recurrent sickness
      absence, continuous long-term sickness absence, and early retirement from the
      labour market. Predictor variables included gender, age, socio-economic position,
      job type, chronic disease status, history of sickness absence, and prior history
      of unemployment. Separate models were built for times of economic growth (2005
      2007) and times of recession (2008-2010). The accuracy of the prediction models
      was assessed with analyses of Receiver Operating Characteristic (ROC) curves and
      the Brier score in an independent validation data set. RESULTS: In comparison
      with a null model which ignored the predictor variables, logistic regression
      achieved only moderate prediction accuracy for the five outcome states. Results
      obtained with discrete event simulation were comparable with logistic regression.
      CONCLUSIONS: Only moderate prediction accuracy could be achieved using the
      selected information from the Danish register RSS. Other variables need to be
      included in order to establish a prediction method which provides more accurate
      risk profiles for long-term sick-listed persons.

PMID- 24885867
TI  - A novel Streptomyces spp. integration vector derived from the S. venezuelae
      phage, SV1.
AB  - BACKGROUND: Integrating vectors based on the int/attP loci of temperate phages
      are convenient and used widely, particularly for cloning genes in Streptomyces
      spp. RESULTS: We have constructed and tested a novel integrating vector based on
      g27, encoding integrase, and attP site from the phage, SV1. This plasmid, pBF3
      integrates efficiently in S. coelicolor and S. lividans but surprisingly fails to
      generate stable integrants in S. venezuelae, the natural host for phage SV1.
      CONCLUSION: pBF3 promises to be a useful addition to the range of integrating
      vectors currently available for Streptomyces molecular genetics.

PMID- 24885868
TI  - Timed Up & Go as a measure for longitudinal change in mobility after stroke -
      Postural Stroke Study in Gothenburg (POSTGOT).
AB  - BACKGROUND: A frequently used clinical test to assess mobility after stroke is
      the Timed Up & Go. Knowledge regarding whether or not the Timed Up & Go is able
      to detect change over time in patients with stroke, whether improvements in
      mobility exist after the first three months and whether or not longitudinal
      change in mobility after stroke depend on the patients' age, is limited or
      unclear. The objectives were to investigate the distribution-based responsiveness
      of the Timed Up & Go (TUG) during the first three months after a first event of
      stroke, to measure the longitudinal change in TUG time during the first year
      after stroke and to establish whether recovery in TUG time differs between
      different age groups. METHODS: Ninety-one patients with first-ever stroke were
      assessed using the Timed Up & Go at the 1st week and at 3, 6 and 12 months after
      stroke. The non-parametric sign-test, the parametric t-test and a mixed model
      approach to linear regression for repeated measurements (Proc mixed) were used
      for the statistical analyses. RESULTS: The median TUG time was reduced from 17 to
      12 seconds (p < 0.001) between the 1st week and 3 months. No further improvement
      was seen between 3 and 12 months after stroke. In a mixed model approach to
      linear regression, there was a significant age difference. Patients at age 80 and
      above tended to deteriorate in terms of TUG time between 3 and 12 months after
      stroke, while patients < 80 years did not (p = 0.011 for the interaction between
      age group and time). CONCLUSION: The Timed Up & Go demonstrates ability to detect
      change in mobility over time in patients with stroke. A significant improvement
      in TUG time from the 1st week to 3 months after stroke was found, as expected,
      but thereafter no statistically significant change was detected. After 3 months,
      patients >=80 years tended to deteriorate in terms of TUG time, while the younger
      patients did not.

PMID- 24885869
TI  - Impact of changed management policies on operating room efficiency.
AB  - BACKGROUND: To increase operating room (OR) efficiency, a new resource allocation
      strategy, a new policy for patient urgency classification, and a new system for
      OR booking was implemented at a tertiary referral hospital. We investigated the
      impact of these interventions. METHODS: We carried out a before-and-after study
      using OR data. A total of 23,515 elective (planned) and non-elective (unplanned)
      orthopaedic and general surgeries were conducted during calendar year 2007
      (period 1) and July 2008 to July 2009 (period 2). The Wilcoxon-Mann-Whitney test
      was used to calculate statistical significance. RESULTS: An increased amount of
      case time (7.1%, p < 0.05) was conducted without any increase in out-of-hours
      case time. Despite having three fewer ORs for electives, slightly more elective
      case time was handled with 26% less use of overtime (p < 0.05). Mean OR
      utilization was 56% for the 17 mixed ORs, 60% for the 14 elective ORs, and 62%
      for the 3 dedicated ORs. A 20% growth (p < 0.05) of non-elective case time was
      primarily absorbed through enhanced daytime surgery, which increased over 48% (p
      < 0.05). As a result, the proportions of case time on evenings and nights
      decreased. Specifically, case time at night decreased by 26% (p < 0.05), and the
      number of nights without surgery increased from 55 to 112 (out of 315 and 316,
      respectively). Median waiting time for the middle urgencies increased with 1.2
      hours, but over 90% received treatment within maximum acceptable waiting time
      (MAWT) in both periods. Median waiting time for the lowest urgencies was reduced
      with 12 hours, and the proportion of cases treated within MAWT increased from 70%
      to 89%. The proportion of high urgency patients (as a proportion of the total)
      was reduced from 20% to 12%. Consequently, almost 90% of the operations could be
      planned at least 24 hours in advance. CONCLUSIONS: The redesign facilitated
      effective daytime surgery and a more selective use of the ORs for high urgency
      patients out of hours. The synergistic effect probably exceeded the sum of the
      individual effects of the changes, because the effects of each intervention
      facilitated the successful implementation of others.

PMID- 24885870
TI  - Diffuse large B cell lymphoma derived from nodular lymphocyte predominant Hodgkin
      lymphoma presents with variable histopathology.
AB  - BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) usually
      presents in middle aged men and shows an indolent clinical behavior. However, up
      to 30% of the patients present a secondary transformation into aggressive diffuse
      large B cell lymphoma (DLBCL). The aim of the present study was to characterize
      morphology and immunophenotype of this kind of DLBCL in detail and compare it
      with conventional DLBCL. METHODS: Morphology and immunophenotype of 33 cases of
      NLPHL with simultaneous or sequential transformation into DLBCL were
      investigated. These cases were compared with 41 de novo DLBCL in Finnish men.
      RESULTS: The majority of cases exhibited different immunophenotypes in the NLPHL
      and the DLBCL components. The immunophenotype of the DLBCL secondary to NLPHL was
      heterogeneous. However, BCL6, EMA, CD75 and J-chain were usually expressed in
      both components (>=73% positive). Overall, the NLPHL component was more
      frequently positive for EMA, CD75 and J-chain than the DLBCL component. In
      contrast, B cell markers, CD10 and BCL2, were more frequently expressed and were
      expressed at higher levels in the DLBCL component than in the NLPHL component. In
      the independent series of de novo DLBCL 4 cases could be identified with a growth
      pattern and immunophenotype that suggested that they had arisen secondarily from
      NLPHL. CONCLUSIONS: The morphology and immunophenotype of DLBCL arisen from NLPHL
      is heterogeneous. Further characterization of the particular molecular features
      of this subgroup is warranted to be able to better identify these cases among
      conventional DLBCL.

PMID- 24885871
TI  - Linoleate appears to protect against palmitate-induced inflammation in Huh7
      cells.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) may protect against metabolic
      diseases. Although the benefits of the n-3 family of PUFA have been well
      investigated in nonalcoholic steatohepatitis (NASH), little is known about the
      effect of the n-6 family. This study examined the effect of linoleate, a member
      of the n-6 family, on regulation of the palmitate-induced inflammatory cytokine
      interleukin-8 (IL8) in hepatocytes. METHODS: Huh7 cells and HepG2 cells were
      cultured with and without free fatty acid treatment (palmitate and linoleate,
      alone or in combination, 100-1000 MUM). Inflammatory pathways, lipid
      accumulation, apoptosis and cell viability were monitored. RESULTS: Dose- and
      time-related changes of IL8 mRNA expression were examined and 9 h treatment with
      500 MUM palmitate showed the greatest elevation of IL8. Co-treatment with 500 MUM
      palmitate and 400 MUM linoleate significantly suppressed IL8 production below
      that with palmitate alone in both cells (both mRNA and protein). A quantitative
      measurement for lipid accumulation showed no significant difference between
      palmitate-treated cells (1.69 +/- 0.21), linoleate-treated cells (1.61 +/- 0.16)
      and palmitate and linoleate-treated cells (1.73 +/- 0.22, NS, n = 7). The co
      treatment with 400 MUM linoleate inhibited phospho-c-Jun N-terminal kinase (pJNK)
      activation and IkBalpha reduction caused by 500 MUM palmitate treatment.
      Treatment with 400 MUM linoleate alone led to IL8 production (5.48 fold change),
      similar to co-treatment, with no influence on the expression of pJNK/IkBalpha.
      The cell viability was similar between treatment with 500 MUM palmitate and with
      both 500 MUM palmitate and 400 MUM linoleate, showing no significant changes in
      the expression of cleaved caspase-3. CONCLUSIONS: Linoleate is a potent regulator
      of the proinflammatory cytokine IL8 via the JNK and nuclear factor kappa B
      pathways that are involved in the pathophysiology of NASH, suggesting a future
      recommendation of dietary management.

PMID- 24885872
TI  - Monte Carlo simulation of laser beams interaction with the human eye using
      Geant4.
AB  - BACKGROUND: Due to the unique characteristics of the eye, ophthalmologic
      diagnostic techniques often rely on the photons interaction with the retina to
      infer its internal structure. Although these techniques are widely used, the
      interpretation of the generated images is not always fully understood, as in
      scanning laser ophthalmoscopy dark field imaging. This limits the exploitation of
      its full potential as a diagnostic tool for deep abnormalities in the retina, as
      in the situation of drusen. METHODS: With the aim of better understanding the
      retinal diagnostic images, we have carried out computer simulations of incident
      laser beams interacting with different structures of the human eye, including a
      retina with and without drusen. We have used the Geant4 simulation toolkit,
      applying the optical package of the electromagnetic (EM) physics working group,
      to simulate the physical processes of reflection, refraction, absorption, and
      scattering of low energy photons (2 eV) in biological tissues. For each
      simulation it was used a single beam of orange light, with a Gaussian profile,
      that travels through all optical elements of the eye. The reflected beam
      characteristics were analyzed by virtual detectors in different locations, which
      collected information about the number and position of photons. The geometry and
      optical properties of all components of the eye were considered according to the
      published data. RESULTS: Simulation results put in evidence that the presence of
      drusen influences the profile of the reflected beams. It changes the mean free
      path of the photons, modifying its reflection pattern, which depends on the area
      illuminated by the incident beam. This result is also visible when the reflected
      beam is analyzed outside of the eye, when the profile has no longer a symmetrical
      Gaussian distribution. These results will support the retinal diagnostic images
      that will be obtained in a near future with a new developed ophthalmic apparatus.
      CONCLUSIONS: The shape analysis of the reflected beams in retinal laser scanning
      techniques could increase its potential as a diagnostic examination tool for the
      deeper structures of the retina.

PMID- 24885873
TI  - Genome variations account for different response to three mineral elements
      between Medicago truncatula ecotypes Jemalong A17 and R108.
AB  - BACKGROUND: Resequencing can be used to identify genome variations underpinning
      many morphological and physiological phenotypes. Legume model plant Medicago
      truncatula ecotypes Jemalong A17 (J. A17) and R108 differ in their responses to
      mineral toxicity of aluminum and sodium, and mineral deficiency of iron in growth
      medium. The difference may result from their genome variations, but no
      experimental evidence supports this hypothesis. RESULTS: A total of 12,750
      structure variations, 135,045 short insertions/deletions and 764,154 single
      nucleotide polymorphisms were identified by resequencing the genome of R108. The
      suppressed expression of MtAACT that encodes a putative aluminum-induced citrate
      efflux transporter by deletion of partial sequence of the second intron may
      account for the less aluminum-induced citrate exudation and greater accumulation
      of aluminum in roots of R108 than in roots of J. A17, thus rendering R108 more
      sensitive to aluminum toxicity. The higher expression-level of MtZpt2-1 encoding
      a TFIIIA-related transcription factor in J. A17 than R108 under conditions of
      salt stress can be explained by the greater number of stress-responsive elements
      in its promoter sequence, thus conferring J. A17 more tolerant to salt stress
      than R108 plants by activating the expression of downstream stress-responsive
      genes. YSLs (Yellow Stripe-Likes) are involved in long-distance transport of iron
      in plants. We found that an YSL gene was deleted in the genome of R108 plants,
      thus rendering R108 less tolerance to iron deficiency than J. A17 plants.
      CONCLUSIONS: The deletion or change in several genes may account for the
      different responses of M. truncatula ecotypes J. A17 and R108 to mineral toxicity
      of aluminum and sodium as well as iron deficiency. Uncovering genome variations
      by resequencing is an effective method to identify different traits between
      species/ecotypes that are genetically related. These findings demonstrate that
      analyses of genome variations by resequencing can shed important light on
      differences in responses of M. truncatula ecotypes to abiotic stress in general
      and mineral stress in particular.

PMID- 24885876
TI  - Numbers and proportions of U.S. military members in treatment for mental
      disorders over time, active component, January 2000-September 2013.
AB  - This report examines trends in health record documentation of the treatment for
      mental disorders of active component U.S. military service members from January
      2000 through September 2013. Inpatient and outpatient records were used to
      estimate the numbers and proportions of service members who received such
      treatment and the durations and intensities of courses of treatment. Annual
      numbers of service members who received treatment for mental disorders and the
      annual numbers of treatment courses increased steadily from 2004-2012. More than
      half of service members who received such treatment had only one treatment
      course, but the annual numbers of such single treatment courses increased by 60%
      during the 13-year surveillance period. Annual numbers of treatment courses that
      consisted of more than 30 encounters increased 5.6-fold between 2001 and 2012 and
      the mean number of days per treatment course markedly increased during the last
      half of the period. The proportion of overall service time contributed by members
      who were in treatment for mental disorders increased from about 1% in 2000 to
      3.5% in 2012. The methods and findings of this analysis are compared and
      contrasted with other published studies and reports about mental health problems
      in the Armed Forces since the beginning of the wars in Afghanistan and Iraq.

PMID- 24885875
TI  - Central retinal vein occlusion in a pediatric patient with SLE and
      antiphospholipid antibodies without anti-cardiolipin or anti-beta2 glycoprotein I
      antibodies.
AB  - BACKGROUND: Antiphospholipid antibody syndrome is characterized by venous and/or
      arterial thrombosis, and is found in patients with systemic lupus erythematosus.
      Its diagnosis requires the presence of both clinical and laboratory findings,
      such as positive anti-cardiolipin and anti-beta2 glycoprotein I antibodies and
      lupus anticoagulant. However, cardiolipin is a minor component of the vascular
      endothelial cells in human, and phosphatidylcholine and phosphatidylethanolamine
      are major components. CASE PRESENTATION: A 15-year-old female suddenly developed
      massive left intraretinal hemorrhaging due to central retinal vein occlusion. She
      also had a butterfly rash, and her laboratory findings revealed positive serum
      anti-nuclear antibodies and decreased serum complement. During this episode, she
      was diagnosed with systemic lupus erythematosus. Although she was negative for
      serum anti-cardiolipin IgG and anti-beta2 glycoprotein I antibodies as well as
      lupus anticoagulant, her serum anti-phosphatidylcholine, anti
      phosphatidylethanolamine, anti-phosphatidylinositol and phosphatidylserine IgG
      antibodies levels were increased. CONCLUSION: Pediatric cases of central retinal
      vein occlusion are rare. Even in patients without anti-cardiolipin or anti-beta2
      glycoprotein I antibodies and lupus anticoagulant, there is the potential for the
      development of antiphospholipid antibody-related thrombosis.

PMID- 24885874
TI  - Down-regulation of mechanisms involved in cell transport and maintenance of
      mucosal integrity in pigs infected with Lawsonia intracellularis.
AB  - Lawsonia intracellularis is an obligate intracellular bacterium, responsible for
      the disease complex known as proliferative enteropathy (PE). L. intracellularis
      is associated with intestinal crypt epithelial cell proliferation but the
      mechanisms responsible are yet to be defined. Microarray analysis was used to
      investigate the host-pathogen interaction in experimentally infected pigs to
      identify pathways that may be involved. Ileal samples originating from twenty
      eight weaner pigs experimentally challenged with a pure culture of L.
      intracellularis (strain LR189/5/83) were subjected to microarray analysis.
      Microarray transcriptional signatures were validated using immunohistochemistry
      and quantitative real time PCR of selected genes at various time points post
      challenge. At peak of infection (14 days post challenge) 86% of altered
      transcripts were down regulated, particularly those involved in maintenance of
      mucosal integrity and regulation of cell transport. Among the up-regulated
      transcripts, CD163 and CDK1 were novel findings and considered to be important,
      due to their respective roles in innate immunity and cellular proliferation.
      Overall, targeted cellular mechanisms included those that are important in
      epithelial restitution, migration and protection; maintenance of stable inter
      epithelial cell relationships; cell transport of nutrients and electrolytes;
      innate immunity; and cell cycle.

PMID- 24885877
TI  - U.S. Armed Forces air crew: incident illness and injury diagnosis during the 12
      months prior to retirement, 2003-2012.
AB  - U.S. Armed Services retirees are eligible for disability compensation for medical
      illness/injury incurred during their service. This analysis of recently retired
      U.S. active component air crew/aviation service members from all Services
      evaluated incident diagnoses among aviation retirees during the 12 months prior
      to retirement and assessed trends in first-time diagnoses by major diagnostic
      category and aviation component stratification. Most aviation retirees were in
      their 40s, Air Force, male, white, and senior officers and warrant officers.
      Among the study population, 14,191 (88%) of aviation retirees had at least one
      first-time diagnosis recorded during the 12 months prior to retirement. During
      2003-2012, 63.8% of all diagnoses in aviation retirees during the 12 months prior
      to retirement were new. The highest proportions of new diagnoses were for "other
      disorders of the ear," "organic sleep disorders," and "general symptoms." Among
      the four subtypes of aviators, general air crew/air craft crew had the lowest
      proportion of new diagnoses (60.2%).

PMID- 24885878
TI  - The geographic distribution of incident Lyme disease among active component
      service members stationed in the continental United States, 2004-2013.

PMID- 24885879
TI  - Injuries associated with combat sports, active component, U.S. Armed Forces, 2010
      2013.
AB  - The practice of combat sports creates a potential for training- and sports
      related injuries among military members. During the 4-year surveillance period,
      there were 12,108 cases of injuries associated with combat sports among active
      component service members; the overall incidence rate was 21.0 per 10,000 person
      years (p-yrs). The rates were higher among service members who were male,
      Hispanic, in the youngest age groups, in the Army, junior enlisted, and in combat
      specific occupations. The rate among recruit/ trainees (779.4 per 10,000 p-yrs)
      was more than 165 times the rate among all other active component service members
      (non-recruits) (4.7 per 10,000 p-yrs). Sprains, strains, and contusions accounted
      for more than one-half of the primary (first-listed) diagnoses associated with
      combat sports cases. More serious conditions such as concussions/head injuries
      and skull/face fractures/intracranial injuries were reported among 3.9% and 2.1%
      of all cases and were more common among boxing-related cases. Hand/wrist
      fractures were also common among boxing cases. Wrestling had comparatively
      greater proportions of dislocations and open wounds. Although the combat sport
      training provides many physical and mental benefits to the individual, safety
      practices should be enforced to reduce the most frequent and serious injuries.

PMID- 24885881
TI  - Long-lasting insecticide-treated bed net ownership and use among children under
      five years of age following a targeted distribution in central Uganda.
AB  - BACKGROUND: Universal coverage of long-lasting insecticide-treated bed nets
      (LLINs) for prevention of malaria was adopted by the Uganda National Malaria
      Control Programme in 2007. The first mass distribution of LLINs was implemented
      in 2010. Initially, a campaign targeted to households with pregnant women and
      children aged <five years was carried out, prior to a planned fill-in campaign to
      achieve universal LLIN coverage. This survey was conducted after the targeted
      distribution in central Uganda to assess progress in LLIN ownership and usage
      among children <five years. METHODS: A two-stage, cluster-sample, cross-sectional
      household survey was carried out in early 2011 in Central region districts
      surveyed during the 2009 Malaria Indicator Survey (MIS). In the first sampling
      stage, 30 enumeration areas (EAs) were selected and all households were
      enumerated. Within each sampled EA, 20 households were randomly selected for
      interview using two questionnaires: a household questionnaire and a woman's
      questionnaire for all women aged 15-49 years, both modified from the MIS.
      RESULTS: When compared to 2009 MIS results, household ownership of at least one
      LLIN increased by 47%, from 22 to 69% after the targeted campaign. LLIN use among
      children <five years increased by 40%, from 11 to 51%. Households with a child
      <six years old at the time of the survey, a proxy for those targeted, were
      significantly more likely to have received a campaign bed net (80.7 vs 35.2%, p <
      0.001). LLIN ownership and use was equitable after the targeted campaign, with no
      significant differences by household wealth status.However, the proportion of
      households with at least one LLIN per two people was still low after the first
      campaign phase, increasing from 8.5 to 25.9%. CONCLUSIONS: The first phase of the
      campaign led to substantial increases in both LLIN ownership and equitable use
      among children <five years in the Central region. However, access to an LLIN
      within the household was still low after the first phase of the campaign,
      indicating the need for the universal fill-in campaign.

PMID- 24885882
TI  - Adverse or acceptable: negotiating access to a post-apartheid health care
      contract.
AB  - BACKGROUND: As in many fragile and post-conflict countries, South Africa's social
      contract has formally changed from authoritarianism to democracy, yet access to
      services, including health care, remains inequitable and contested. We examine
      access barriers to quality health services and draw on social contract theory to
      explore ways in which a post-apartheid health care contract is narrated,
      practiced and negotiated by patients and providers. We consider implications for
      conceptualizing and promoting more inclusive, equitable health services in a post
      conflict setting. METHODS: Using in-depth interviews with 45 patients and 67
      providers, and field observations from twelve health facilities in one rural and
      two urban sub-districts, we explore access narratives of those seeking and
      delivering - negotiating - maternal health, tuberculosis and antiretroviral
      services in South Africa. RESULTS: Although South Africa's right to access to
      health care is constitutionally guaranteed, in practice, a post-apartheid health
      care contract is not automatically or unconditionally inclusive. Access barriers,
      including poverty, an under-resourced, hierarchical health system, the nature of
      illness and treatment, and negative attitudes and actions, create conditions for
      insecure or adverse incorporation into this contract, or even exclusion
      (sometimes temporary) from health care services. Such barriers are exacerbated by
      differences in the expectations that patients and providers have of each other
      and the contract, leading to differing, potentially conflicting, identities of
      inclusion and exclusion: defaulting versus suffering patients, uncaring versus
      overstretched providers. Conversely, caring, respectful communication, individual
      acts of kindness, and institutional flexibility and leadership may mitigate key
      access barriers and limit threats to the contract, fostering more positive forms
      of inclusion and facilitating easier access to health care. CONCLUSIONS: Building
      health in fragile and post-conflict societies requires the negotiation of a new
      social contract. Surfacing and engaging with differences in patient and provider
      expectations of this contract may contribute to more acceptable, accessible
      health care services. Additionally, the health system is well positioned to
      highlight and connect the political economy, institutions and social
      relationships that create and sustain identities of exclusion and inclusion -
      (re)politicise suffering - and co-ordinate and lead intersectoral action for
      overcoming affordability and availability barriers to inclusive and equitable
      health care services.

PMID- 24885883
TI  - Comparison of different extraction techniques to profile microRNAs from human
      sera and peripheral blood mononuclear cells.
AB  - BACKGROUND: microRNAs (miRNAs) play crucial roles in major biological processes
      and their deregulations are often associated with human malignancies. As such,
      they represent appealing candidates as targets of innovative therapies. Another
      interesting aspect of their biology is that they are present in various
      biological fluids where, advantageously, they appear to be very stable. A
      plethora of studies have now reported their potential as biomarkers that can be
      used in diagnosis, prognosis and/or theranostic issues. However, the application
      of circulating miRNAs in clinical practices still requires the identification of
      highly efficient, robust and reproducible methods for their isolation from
      biological samples.In that context, we performed an independent cross-comparison
      of three commercially available RNA extraction kits for miRNAs isolation from
      human blood samples (Qiagen and Norgen kits as well as the new NucleoSpin miRNAs
      Plasma kit from Macherey-Nagel). miRNAs were further profiled using the Taqman
      Low Density Array technology. RESULTS: We found that, although these 3 kits had
      equal performances in extracting miRNAs from peripheral blood mononuclear cells,
      the Macherey-Nagel kit presented several advantages when isolating miRNAs from
      sera. Besides, our results have indicated that, depending on the quantity of the
      biological samples used, the extraction procedure directly impacted on the G/C
      composition of the miRNAs detected. CONCLUSION: Overall, our study contributes to
      the definition of a reliable framework for profiling circulating miRNAs.

PMID- 24885884
TI  - PapMV nanoparticles improve mucosal immune responses to the trivalent inactivated
      flu vaccine.
AB  - BACKGROUND: Trivalent inactivated flu vaccines (TIV) are currently the best means
      to prevent influenza infections. However, the protection provided by TIV is
      partial (about 50%) and it is needed to improve the efficacy of protection. Since
      the respiratory tract is the main site of influenza replications, a vaccine that
      triggers mucosal immunity in this region can potentially improve protection
      against this disease. Recently, PapMV nanoparticles used as an adjuvant in a
      formulation with TIV administered by the subcutaneous route have shown improving
      the immune response directed to the TIV and protection against an influenza
      challenge. FINDINGS: In the present study, we showed that intranasal instillation
      with a formulation containing TIV and PapMV nanoparticles significantly increase
      the amount of IgG, IgG2a and IgA in lungs of vaccinated mice as compared to mice
      that received TIV only. Instillation with the adjuvanted formulation leads to a
      more robust protection against an influenza infection with a strain that is
      lethal to mice vaccinated with the TIV. CONCLUSIONS: We demonstrate for the first
      time that PapMV nanoparticles are an effective and potent mucosal adjuvant for
      vaccination.

PMID- 24885887
TI  - Low birth weight in Sao Luis, northeastern Brazil: trends and associated factors.
AB  - BACKGROUND: To analyze trends in LBW (low birth weight) rate using birth registry
      data and identify factors associated with LBW in Sao Luis comparing two birth
      cohorts separated by a 12-year interval. METHODS: 2,426 births were included in
      1997/98 and 5,040 in 2010. The dependent variable was LBW (<2,500 g). Multiple
      logistic regression was performed to determine the association of independent
      variables with LBW. Data were also obtained from SINASC (Brazilian National Birth
      Registry) to analyze stillbirth and LBW rates trends from 1996 to 2010, using 3
      year moving averages. RESULTS: LBW, intrauterine growth restriction (IUGR) and
      preterm birth rates did not differ between the two cohorts. Despite this, birth
      registry data showed increasing LBW rate up to 2001, coinciding with decreasing
      stillbirth rate. Both stillbirth and LBW rates decreased thereafter. A
      significant reduction was observed in the percentage of teenage mothers, mothers
      with up to 4 years of education, family income up to one minimum wage and mothers
      who did not attend prenatal care. There was an increase in maternal age >=35
      years and schooling >=12 years. The variables associated with LBW in 1997/98 were
      young maternal age (<18 years), maternal smoking during pregnancy and
      primiparity. Variables that remained in the adjusted model in 2010 were female
      gender, income <3 minimum wages, lack of prenatal care, maternal smoking during
      pregnancy and primiparity. CONCLUSIONS: Although LBW rate did not differ between
      the two cohorts, this apparent stability masked an increase up to 2001 and a
      decrease thereafter. The rise in LBW rate paralleled reduction in the stillbirth
      rate, suggesting improvement in obstetrical and newborn care. Maternal,
      socioeconomic and demographic factors associated with LBW differed between the
      two cohorts, except for smoking during pregnancy and parity that were
      significantly associated with LBW in both cohorts.

PMID- 24885886
TI  - Epidermal growth factor receptor mutations and anaplastic lymphoma kinase
      rearrangements in lung cancer with nodular ground-glass opacity.
AB  - BACKGROUND: Nodular ground-glass opacities (nGGO) are a specific type of lung
      adenocarcinoma. ALK rearrangements and driver mutations such as EGFR and K-ras
      are frequently found in all types of lung adenocarcinoma. EGFR mutations play a
      role in the early carcinogenesis of nGGOs, but the role of ALK rearrangement
      remains unknown. METHODS: We studied 217 nGGOs resected from 215 lung cancer
      patients. Pathology, tumor size, tumor disappearance rate, and the EGFR and ALK
      markers were analyzed. RESULTS: All but one of the resected nGGOs were
      adenocarcinomas. ALK rearrangements and EGFR mutations were found in 6 (2.8%) and
      119 (54.8%) cases. The frequency of ALK rearrangement in nGGO was significantly
      lower than previously reported in adenocarcinoma. Advanced disease stage (p =
      0.018) and larger tumor size (p = 0.037) were more frequent in the ALK
      rearrangement-positive group than in ALK rearrangement-negative patients. nGGOs
      with ALK rearrangements were associated with significantly higher pathologic
      stage and larger maximal and solid diameter in comparison to EGFR-mutated
      lesions. CONCLUSION: ALK rearrangement is rare in lung cancer with nGGOs, but is
      associated with advanced stage and larger tumor size, suggesting its association
      with aggressive progression of lung adenocarcinoma. ALK rearrangement may not be
      important in early pathogenesis of nGGO.

PMID- 24885888
TI  - Experiences of patients identifying with chronic Lyme disease in the healthcare
      system: a qualitative study.
AB  - BACKGROUND: Chronic Lyme disease is a term that describes a constellation of
      persistent symptoms in patients with or without evidence of previous Borrelia
      burgdorferi infection. Patients labeled as having chronic Lyme disease have a
      substantial clinical burden. Little is known about chronic Lyme disease patient
      experiences in the healthcare system and their relationships with healthcare
      providers. The purpose of this study was to gather insights about the experiences
      of patients who carry a diagnosis of chronic Lyme disease in the United States
      healthcare system. METHODS: Qualitative, phenomenological study in 12 adult
      participants who identified themselves as having chronic Lyme disease. Semi
      structured face-to-face in-depth interviews were conducted, 60-90 minutes in
      length, focusing on perceptions of disease burden and of their healthcare
      providers, using the dimensions of the Health Belief Model. Transcribed
      interviews were analyzed for emergent topics and themes in the categories of
      beliefs/understanding, personal history/narrative, consequences/limitations,
      management, and influences on care. RESULTS: Enrollment continued until
      theoretical saturation was obtained. Four major themes emerged from participants'
      descriptions of their experiences and perceptions: 1) changes in health status
      and the social impact of chronic Lyme disease, 2) doubts about recovery and the
      future, 3) contrasting doctor-patient relationships, 4) and the use of
      unconventional therapies to treat chronic Lyme disease. CONCLUSIONS: Participants
      reported a significant decline in health status associated with chronic Lyme
      disease and were often unsatisfied with care in conventional settings. Negative
      experiences were associated with reports of dismissive, patronizing, and
      condescending attitudes. Positive experiences were associated with providers who
      were reported to be attentive, optimistic, and supportive. Consultations with CAM
      practitioners and use of CAM therapies were common. Actively engaged and
      sympathetic clinical encounters may foster greater satisfaction in healthcare
      settings.

PMID- 24885889
TI  - Efficacy of a modern neuroscience approach versus usual care evidence-based
      physiotherapy on pain, disability and brain characteristics in chronic spinal
      pain patients: protocol of a randomized clinical trial.
AB  - BACKGROUND: Among the multiple conservative modalities, physiotherapy is a
      commonly utilized treatment modality in managing chronic non-specific spinal
      pain. Despite the scientific progresses with regard to pain and motor control
      neuroscience, treatment of chronic spinal pain (CSP) often tends to stick to a
      peripheral biomechanical model, without targeting brain mechanisms. With a view
      to enhance clinical efficacy of existing physiotherapeutic treatments for CSP,
      the development of clinical strategies targeted at 'training the brain' is to be
      pursued. Promising proof-of-principle results have been reported for the
      effectiveness of a modern neuroscience approach to CSP when compared to usual
      care, but confirmation is required in a larger, multi-center trial with
      appropriate evidence-based control intervention and long-term follow-up.The aim
      of this study is to assess the effectiveness of a modern neuroscience approach,
      compared to usual care evidence-based physiotherapy, for reducing pain and
      improving functioning in patients with CSP. A secondary objective entails
      examining the effectiveness of the modern neuroscience approach versus usual care
      physiotherapy for normalizing brain gray matter in patients with CSP.
      METHODS/DESIGN: The study is a multi-center, triple-blind, two-arm (1:1)
      randomized clinical trial with 1-year follow-up. 120 CSP patients will be
      randomly allocated to either the experimental (receiving pain neuroscience
      education followed by cognition-targeted motor control training) or the control
      group (receiving usual care physiotherapy), each comprising of 3 months
      treatment. The main outcome measures are pain (including symptoms and indices of
      central sensitization) and self-reported disability. Secondary outcome measures
      include brain gray matter structure, motor control, muscle properties, and
      psychosocial correlates. Clinical assessment and brain imaging will be performed
      at baseline, post-treatment and at 1-year follow-up. Web-based questionnaires
      will be completed at baseline, after the first 3 treatment sessions, post
      treatment, and at 6 and 12-months follow-up. DISCUSSION: Findings may provide
      empirical evidence on: (1) the effectiveness of a modern neuroscience approach to
      CSP for reducing pain and improving functioning, (2) the effectiveness of a
      modern neuroscience approach for normalizing brain gray matter in CSP patients,
      and (3) factors associated with therapy success. Hence, this trial might
      contribute towards refining guidelines for good clinical practice and might be
      used as a basis for health authorities' recommendations. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02098005.

PMID- 24885891
TI  - Visualization of blood supply route to the reconstructed stomach by indocyanine
      green fluorescence imaging during esophagectomy.
AB  - BACKGROUND: Ensuring an adequate blood supply is essential to the safe
      performance of an anastomosis during esophagectomy and the prevention of
      anastomotic leakage. Recently, indocyanine green (ICG) fluorescence imaging has
      been used to visualize the blood supply when anastomosis is performed in vascular
      surgery. We used ICG fluorescence imaging to visualize the blood supply for
      reconstruction during esophagectomy. METHODS: Since January 2009, we have
      performed ICG fluorescence imaging in 33 patients with thoracic esophageal cancer
      who underwent thoracic esophagectomy. After pulling up the reconstructed stomach,
      2.5 mg of ICG was injected as a bolus. ICG fluorescence imaging was performed
      with a near-infrared camera, and the images were recorded. RESULTS: ICG
      fluorescence was easily detected in all patients 1 min after injection. Vascular
      networks were well visualized in the gastric wall and omentum. The blood supply
      route was located in the greater omentum beside the splenic hilum in 22 (66.7%)
      of the 33 patients. CONCLUSIONS: ICG fluorescence can be used to evaluate the
      blood supply to the reconstructed stomach in patients undergoing esophagectomy
      for esophageal cancer. On ICG fluorescence imaging, the splenic hiatal vessels
      were the major blood supply for the anastomosis in most patients.

PMID- 24885890
TI  - Antagonism of sorafenib and regorafenib actions by platelet factors in
      hepatocellular carcinoma cell lines.
AB  - BACKGROUND: Platelets are frequently altered in hepatocellular carcinoma (HCC)
      patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease
      apoptosis. The aims were to evaluate whether hPL can modulate the actions of
      sorafenib or regorafenib, two clinical HCC multikinase antagonists. METHODS:
      Several human HCC cell lines were grown in the presence and absence of sorafenib
      or regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis
      was assessed by Annexin V and by western blot, and autophagy and MAPK growth
      signaling were also measured by western blot, and migration and invasion were
      measured by standard in vitro assays. RESULTS: Both sorafenib and regorafenib
      mediated inhibition of cell growth, migration and invasion were all antagonized
      by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both
      blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL
      levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin
      like growth factor-I (IGF-I), included in hPL, revealed that these factors were
      able to antagonized sorafenib in a proliferation assay, in particular when used
      in combination. CONCLUSIONS: Platelet factors can antagonize sorafenib or
      regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation
      of platelet activity or numbers has the potential to enhance multikinase drug
      actions.

PMID- 24885892
TI  - Pulmonary blastoma: a case report and review of the literature.
AB  - BACKGROUND: Pulmonary blastomas are a rare aggressive neoplasm comprising 0.25
      0.5% of all primary lung tumors and portend a poor prognosis. They display a
      biphasic histology with mesenchymal and epithelial components. Historically, the
      term pulmonary blastoma had included both pure fetal adenocarcinomas,
      pleuropulmonary blastomas as well as the classic biphasic blastomas. However
      recent World Health Organisation re-classifications separated well-differentiated
      fetal adenocarcinomas and pleuropulmonary blastomas from the biphasic tumours.
      CASE PRESENTATION: We present a case of a systemically well 67-year-old Caucasian
      male who presented with haemoptysis. Investigations confirmed the presence of a
      large right-sided lung mass and biopsy identified non-small cell carcinoma. The
      resected tumour was markedly necrotic revealing a biphasic pattern. It was
      composed of malignant glandular tissue with sub-nuclear vacuoles, associated with
      a pleomorphic stromal malignant blastematous component, characteristic of classic
      biphasic pulmonary blastoma. CONCLUSION: We present a case of a classic biphasic
      pulmonary blastoma, a rare lung cancer occurring at an earlier age and portending
      to poorer prognosis than other more common lung cancers. Given the small number
      of cases and recent re-classification, interpreting the published epidemiology
      and clinical features of this disease is difficult. Many earlier reports may have
      included fetal adenocarcinomas (in particular high grade variant), which need to
      be considered when discussing treatment and prognosis with newly-diagnosed
      patients. Much could be gained from a central registry of individual experiences
      to improve our understanding of this rare lung cancer.

PMID- 24885893
TI  - Efficient clinical evaluation of guideline quality: development and testing of a
      new tool.
AB  - BACKGROUND: Evaluating the methodological quality of clinical practice guidelines
      is essential before deciding which ones which could best inform policy or
      practice. One current method of evaluating clinical guideline quality is the
      research-focused AGREE II instrument. This uses 23 questions scored 1-7, arranged
      in six domains, which requires at least two independent testers, and uses a
      formulaic weighted domain scoring system. Following feedback from time-poor
      clinicians, policy-makers and managers that this instrument did not suit clinical
      need, we developed and tested a simpler, shorter, binary scored instrument (the
      iCAHE Guideline Quality Checklist) designed for single users. METHODS: Content
      and construct validity, inter-tester reliability and clinical utility were tested
      by comparing the new iCAHE Guideline Quality Checklist with the AGREE II
      instrument. Firstly the questions and domains in both instruments were compared.
      Six randomly-selected guidelines on a similar theme were then assessed by three
      independent testers with different experience in guideline quality assessment,
      using both instruments. Per guideline, weighted domain and total AGREE II scores
      were calculated, using the scoring rubric for three testers. Total iCAHE scores
      were calculated per guideline, per tester. The linear relationship between iCAHE
      and AGREE II scores was assessed using Pearson r correlation coefficients. Score
      differences between testers were assessed for the iCAHE Guideline Quality
      Checklist. RESULTS: There were congruent questions in each instrument in four
      domains (Scope & Purpose, Stakeholder involvement, Underlying evidence/Rigour,
      Clarity). The iCAHE and AGREE II scores were moderate to strongly correlated for
      the six guidelines. There was generally good agreement between testers for iCAHE
      scores, irrespective of their experience. The iCAHE instrument was preferred by
      all testers, and took significantly less time to administer than the AGREE II
      instrument. However, the use of only three testers and six guidelines compromised
      study power, rendering this research as pilot investigations of the psychometric
      properties of the iCAHE instrument. CONCLUSION: The iCAHE Guideline Quality
      Checklist has promising psychometric properties and clinical utility.

PMID- 24885894
TI  - A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in
      pollen-induced seasonal allergic rhinoconjunctivitis.
AB  - BACKGROUND: The capacity of sublingual allergen immunotherapy (SLIT) to provide
      effective symptom relief in pollen-induced seasonal allergic rhinitis is often
      questioned, despite evidence of clinical efficacy from meta-analyses and well
      powered, double-blind, placebo-controlled randomized clinical trials. In the
      absence of direct, head-to-head, comparative trials of SLIT and symptomatic
      medication, only indirect comparisons are possible. METHODS: We performed a meta
      analysis of classes of products (second-generation H1-antihistamines, nasal
      corticosteroids and grass pollen SLIT tablet formulations) and single products
      (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor
      antagonist montelukast) for the treatment of seasonal allergic rhinitis in
      adults, adolescents and/or children. We searched the literature for large (n >100
      in the smallest treatment arm) double-blind, placebo-controlled randomized
      clinical trials. For each drug or drug class, we performed a meta-analysis of the
      effect on symptom scores. For each selected trial, we calculated the relative
      clinical impact (according to a previously published method) on the basis of the
      reported post-treatment or season-long nasal or total symptom scores: 100 *
      (scorePlacebo - scoreActive)/scorePlacebo. RESULTS: Twenty-eight publications on
      symptomatic medication trials and ten on SLIT trials met our selection criteria
      (total number of patients: n = 21,223). The Hedges' g values from the meta
      analyses confirmed the presence of a treatment effect for all drug classes. In an
      indirect comparison, the weighted mean (range) relative clinical impacts were 
      29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for
      timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, 
      17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and 
      6.5% (-3% to -10%) for montelukast. CONCLUSIONS: In an indirect comparison, grass
      pollen SLIT tablets had a greater mean relative clinical impact than second
      generation antihistamines and montelukast and much the same mean relative
      clinical impact as nasal corticosteroids. This result was obtained despite the
      presence of methodological factors that mask the clinical efficacy of SLIT for
      the treatment of seasonal allergic rhinitis.

PMID- 24885896
TI  - The biochemical recurrence-free rate in patients who underwent prostate low-dose
      rate brachytherapy, using two different definitions.
AB  - BACKGROUND: To assess the biochemical recurrence (BCR)-free rate in patients who
      underwent prostate low-dose-rate brachytherapy (LDR-brachytherapy), using two
      different definitions (Phoenix definition and PSA >= 0.2 ng/mL). METHODS: Two
      hundreds and three patients who were clinically diagnosed with localized prostate
      cancer (cT1c-2cN0M0) and underwent LDR-brachytherapy between July 2004 and
      September 2008 were enrolled. The median follow-up period was 72 months. We
      evaluated the BCR-free rate using the Phoenix definition and the PSA cut-off
      value of 0.2 ng/mL, as in the definition for radical prostatectomy. To evaluate
      an independent variable that can predict BCR, Cox's proportional hazard
      regression analysis was carried out. RESULTS: The BCR-free rate in patients using
      the Phoenix definition was acceptable (5-year: 92.8%). The 5- year BCR-free rate
      using the strict definition (PSA >= 0.2 ng/mL) was 74.1%. Cox's proportional
      hazard regression analysis showed that a higher biological effective dose (BED)
      of >=180 Gy2 was the only independent variable that could predict BCR (HR: 0.570,
      95% C.I.: 0.327-0.994, p = 0.048). Patients with a higher BED (>=180 Gy2) had a
      significantly higher BCR-free rate than those with a lower BED (<180 Gy2) (5-year
      BCR-free rate: 80.5% vs. 67.4%). CONCLUSIONS: A higher BED >=180 Gy2 promises a
      favorable BCR-free rate, even if the strict definition is adopted.

PMID- 24885895
TI  - Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to
      regulate inflammasome activation.
AB  - BACKGROUND: Asbestos exposure is related to various diseases including asbestosis
      and malignant mesothelioma (MM). Among the pathogenic mechanisms proposed by
      which asbestos can cause diseases involving epithelial and mesothelial cells, the
      most widely accepted one is the generation of reactive oxygen species and/or
      depletion of antioxidants like glutathione. It has also been demonstrated that
      asbestos can induce inflammation, perhaps due to activation of inflammasomes.
      METHODS: The oxidation state of thioredoxin was analyzed by redox Western blot
      analysis and ROS generation was assessed spectrophotometrically as a read-out of
      solubilized formazan produced by the reduction of nitrotetrazolium blue (NTB) by
      superoxide. Quantitative real time PCR was used to assess changes in gene
      transcription. RESULTS: Here we demonstrate that crocidolite asbestos fibers
      oxidize the pool of the antioxidant, Thioredoxin-1 (Trx1), which results in
      release of Thioredoxin Interacting Protein (TXNIP) and subsequent activation of
      inflammasomes in human mesothelial cells. Exposure to crocidolite asbestos
      resulted in the depletion of reduced Trx1 in human peritoneal mesothelial
      (LP9/hTERT) cells. Pretreatment with the antioxidant dehydroascorbic acid (a
      reactive oxygen species (ROS) scavenger) reduced the level of crocidolite
      asbestos-induced Trx1 oxidation as well as the depletion of reduced Trx1.
      Increasing Trx1 expression levels using a Trx1 over-expression vector, reduced
      the extent of Trx1 oxidation and generation of ROS by crocidolite asbestos, and
      increased cell survival. In addition, knockdown of TXNIP expression by siRNA
      attenuated crocidolite asbestos-induced activation of the inflammasome.
      CONCLUSION: Our novel findings suggest that extensive Trx1 oxidation and TXNIP
      dissociation may be one of the mechanisms by which crocidolite asbestos activates
      the inflammasome and helps in development of MM.

PMID- 24885897
TI  - Integrating respiratory-gated PET-based target volume delineation in liver SBRT
      planning, a pilot study.
AB  - BACKGROUND: To assess the feasibility and benefit of integrating four-dimensional
      (4D) Positron Emission Tomography (PET) - computed tomography (CT) for liver
      stereotactic body radiation therapy (SBRT) planning. METHODS: 8 patients with 14
      metastases were accrued in the study. They all underwent a non-gated PET and a 4D
      PET centered on the liver. The same CT scan was used for attenuation correction,
      registration, and considered the planning CT for SBRT planning. Six PET phases
      were reconstructed for each 4D PET. By applying an individualized threshold to
      the 4D PET, a Biological Internal Target Volume (BITV) was generated for each
      lesion. A gated Planning Target Volume (PTVg) was created by adding 3 mm to
      account for set-up margins. This volume was compared to a manual Planning Target
      Volume (PTV) delineated with the help of a semi-automatic Biological Target
      Volume (BTV) obtained from the non-gated exam. A 5 mm radial and a 10 mm
      craniocaudal margins were applied to account for tumor motion and set-up margins
      to create the PTV. RESULTS: One undiagnosed liver metastasis was discovered
      thanks to the 4D PET. The semi-automatic BTV were significantly smaller than the
      BITV (p = 0.0031). However, after applying adapted margins, 4D PET allowed a
      statistically significant decrease in the PTVg as compared to the PTV (p =
      0.0052). CONCLUSIONS: In comparison to non-gated PET, 4D PET may better define
      the respiratory movements of liver targets and improve SBRT planning for liver
      metastases. Furthermore, non respiratory-gated PET exams can both misdiagnose
      liver metastases and underestimate the real internal target volumes.

PMID- 24885898
TI  - Taurine improves the spatial learning and memory ability impaired by sub-chronic
      manganese exposure.
AB  - BACKGROUND: Excessive manganese exposure induced cognitive deficit. Several lines
      of evidence have demonstrated that taurine improves cognitive impairment induced
      by numerous neurotoxins. However, the role of taurine on manganese-induced
      damages in learning and memory is still elusive. This goal of this study was to
      investigate the beneficial effect of taurine on learning and memory capacity
      impairment by manganese exposure in an animal model. RESULTS: The escape latency
      in the Morris Water Maze test was significantly longer in the rats injected with
      manganese than that in the rats received both taurine and manganese. Similarly,
      the probe trial showed that the annulus crossings were significantly greater in
      the taurine plus manganese treated rats than those in the manganese-treated rats.
      However, the blood level of manganese was not altered by the taurine treatment.
      Interestingly, the exposure of manganese led to a significant increase in the
      acetylcholinesterase activity and an evidently decrease in the choline
      acetyltransferase activity, which were partially restored by the addition of
      taurine. Additionally, we identified 9 differentially expressed proteins between
      the rat hippocampus treated by manganese and the control or the manganese plus
      taurine in the proteomic analysis using the 2-dimensional gel electrophoresis
      followed by the tandem mass spectrometry (MS/MS). Most of these proteins play a
      role in energy metabolism, oxidative stress, inflammation, and neuron synapse.
      CONCLUSIONS: In summary, taurine restores the activity of AChE and ChAT, which
      are critical for the regulation of acetylcholine. We have identified seven
      differentially expressed proteins specifically induced by manganese and two
      proteins induced by taurine from the rat hippocampus. Our results support that
      taurine improves the impaired learning and memory ability caused by excessive
      exposure of manganese.

PMID- 24885899
TI  - Obesity is associated with increased seminal insulin and leptin alongside reduced
      fertility parameters in a controlled male cohort.
AB  - BACKGROUND: Obesity appears to be associated with male reproductive dysfunction
      and infertility, although this has been inconsistent and inconclusive. Insulin
      and leptin are known mediators and modulators of the hypothalamus-pituitary
      testes axis, contributing to the regulation of male reproductive potential and
      overall wellbeing. These hormones are also present in semen influencing sperm
      functions. Although abdominal obesity is closely associated with insulin
      resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes
      in seminal plasma concentrations of insulin, leptin and glucose in obese males
      has not previously been investigated. METHODS: This small case controlled study
      assessed serum and seminal concentrations of insulin, leptin and glucose in obese
      (BMI > =30; n = 23) and non-obese (BMI < 30; n = 19) males. Following a detailed
      medical history and examination, participants meeting the inclusion criteria were
      entered for data analysis. Body parameters such as BMI, waist and hip
      circumference and the waist hip ratio were measured. Serum and semen samples were
      collected and assayed for insulin, leptin and glucose. Semen samples also
      underwent a standard semen analysis, with sperm mitochondrial membrane potential
      (MMP) and DNA fragmentation (DF). RESULTS: Obesity was associated with increased
      serum and seminal insulin and leptin, with no significant difference in seminal
      glucose. Serum and seminal concentrations of insulin and leptin were positively
      correlated. Furthermore, obesity was associated with decreased sperm
      concentration, sperm vitality and increased MMP and DF, with a non-significant
      impact on motility and morphology. CONCLUSIONS: Hyperinsulinaemia and
      hyperleptinaemia are associated with increased seminal insulin and leptin
      concentrations, which may negatively impact male reproductive function in
      obesity. Insulin was also found to be highly concentrated in the seminal plasma
      of both groups. This data will contribute to the contradictive information
      available in the literature on the impact of obesity and male reproduction.

PMID- 24885900
TI  - Oxygen stress reduces zoospore survival of Phytophthora species in a simulated
      aquatic system.
AB  - BACKGROUND: The genus Phytophthora includes a group of agriculturally important
      pathogens and they are commonly regarded as water molds. They produce motile
      zoospores that can move via water currents and on their own locomotion in aquatic
      environments. However, zoosporic response to dissolved oxygen, an important water
      quality parameter, is not known. Like other water quality parameters, dissolved
      oxygen concentration in irrigation reservoirs fluctuates dramatically over time.
      The aim of this study was to determine whether and how zoospore survival may be
      affected by elevated and low concentrations of dissolved oxygen in water to
      better understand the aquatic biology of these pathogens in irrigation
      reservoirs. RESULTS: Zoospores of P. megasperma, P. nicotianae, P. pini and P.
      tropicalis were assessed for survival in 10% Hoagland's solution at a range of
      dissolved concentrations from 0.9 to 20.1 mg L(-1) for up to seven exposure times
      from 0 to 72 h. Zoospore survival was measured by resultant colony counts per ml.
      Zoospores of these species survived the best in control Hoagland's solution at
      dissolved oxygen concentrations of 5.3 to 5.6 mg L(-1). Zoospore survival rates
      decreased with increasing and decreasing concentration of dissolved oxygen,
      depending upon Phytophthora species and exposure time. Overall, P. megasperma and
      P. pini are less sensitive than P. nicotianae and P. tropicalis to hyperoxia and
      hypoxia conditions. CONCLUSION: Zoospores in the control solution declined over
      time and this natural decline process was enhanced under hyperoxia and hypoxia
      conditions. These findings suggest that dramatic fluctuations of dissolved oxygen
      in irrigation reservoirs contribute to the population decline of Phytophthora
      species along the water path in the same reservoirs. These findings advanced our
      understanding of the aquatic ecology of these pathogens in irrigation reservoirs.
      They also provided a basis for pathogen risk mitigation by prolonging the
      turnover time of runoff water in recycling irrigation systems via better system
      designs.

PMID- 24885902
TI  - Long-term survey of a syringe-dispensing machine needle exchange program:
      answering public concerns.
AB  - BACKGROUND: Syringe-dispensing machines (SDM) provide syringes at any time even
      to hard-to-reach injecting drug users (IDUs). They represent an important harm
      reduction strategy in large populated urban areas such as Paris. We analyzed the
      performance of one of the world's largest SDM schemes based in Paris over 12
      years to understand its efficiency and its limitations, to answer public and
      stakeholder concerns and optimize its outputs. METHODS: Parisian syringe
      dispensing and exchange machines were monitored as well as their sharp disposals
      and associated bins over a 12-year period. Moreover, mechanical counting devices
      were installed on specific syringe-dispensing/exchange machines to record the
      characteristics of the exchange process. RESULTS: Distribution and needle
      exchange have risen steadily by 202% for the distribution and 2,000% for syringe
      recovery even without a coin counterpart. However, 2 machines out of 34 generate
      50% of the total activity of the scheme. It takes 14 s for an IDU to collect a
      syringe, while the average user takes 3.76 syringes per session 20 min apart.
      Interestingly, collection time stops early in the evening (19 h) for the entire
      night. CONCLUSIONS: SDMs had an increasing distribution role during daytime as
      part of the harm reduction strategy in Paris with efficient recycling capacities
      of used syringes and a limited number of kits collected by IDU. Using counting
      devices to monitor Syringe Exchange Programs (SEPs) is a very helpful tool to
      optimize use and answer public and stakeholder concerns.

PMID- 24885901
TI  - Development of an immunochromatography strip test based on truncated nucleocapsid
      antigens of three representative hantaviruses.
AB  - BACKGROUND: Hantaviruses are causative agents of hemorrhagic fever with renal
      syndrome (HFRS) and nephropathia epidemica (NE) in the Old World and hantavirus
      pulmonary syndrome (HPS) in the New World. There is a need for time-saving
      diagnostic methods. In the present study, recombinant N antigens were used as
      antigens in an immunochromatography strip (ICG) test to detect specific IgG
      antibodies. METHODS: The N-terminal 103 amino acids (aa) of Hantaan virus (HTNV),
      Puumala virus (PUUV) and Andes virus (ANDV) nucleocapsid (N) protein were
      expressed in E. coli as representative antigens of three groups (HFRS, NE and HPS
      causing viruses) of hantavirus. Five different types of ICG test strips, one
      antigen line on one strip for each of the three selected hantaviruses (HTNV, PUUV
      and ANDV), three antigen lines on one strip and a mixed antigen line on one
      strip, were developed and sensitivities were compared. RESULTS: A total of 87
      convalescent-phase patient sera, including sera from 35 HFRS patients, 36 NE
      patients and 16 HPS patients, and 25 sera from healthy seronegative people as
      negative controls were used to evaluate the ICG test. Sensitivities of the three
      line strip and mixed-line strip were similar to those of the single antigen strip
      (97.2 to 100%). On the other hand, all of the ICG test strips showed high
      specificities to healthy donors. CONCLUSION: These results indicated that the ICG
      test with the three representative antigens is an effective serodiagnostic tool
      for screening and typing of hantavirus infection in humans.

PMID- 24885903
TI  - Larvicidal effect of disinfectant soap on Anopheles gambiae s.s (Diptera:
      Culicidae) in laboratory and semifield environs.
AB  - BACKGROUND: Mosquito larval control using chemicals and biological agents is of
      paramount importance in vector population and disease incidence reduction. A
      commercial synthetic disinfectant soap was evaluated against larvae of Anopheles
      gambiae s.s. in both laboratory and semi field conditions. METHOD: Five
      concentrations of commercial synthetic disinfectant soap (0.0001, 0.001, 0.01,
      0.1 and 1%) were prepared and evaluated against third instar larvae in laboratory
      and semi field environments. Mortality was scored at 12, 24, 48, and 72 hrs. Each
      dosage had 6 replicates, having twenty 3rd instar larvae of An.gambiae s.s.
      RESULTS: In the laboratory phase, all dosages had significantly higher larval
      mortalities than in controls, while in semi field conditions, the dosages of
      0.0001, 0.001 and 0.01% had lower mortalities than laboratory trials. In the
      comparison between semi field and laboratory trials, only 0.1 and 1% dosage had
      significant difference with more mortality in semifield conditions. Proportions
      of larvae that died during mortality monitoring intervals in laboratory and semi
      field had significant differences only at 12 hrs and 72 hrs. CONCLUSION: The
      findings of this study have demonstrated that the mortality of larvae caused by
      commercial synthetic disinfectant soap is worth further studies in open water
      bodies. More studies are necessary to find out the effect of sunlight on the
      chemistry of the synthetic disinfectant and other variables in small scale full
      field trials.

PMID- 24885904
TI  - The DiaS trial: dialectical behavior therapy versus collaborative assessment and
      management of suicidality on self-harm in patients with a recent suicide attempt
      and borderline personality disorder traits - study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: In Denmark 8,000 to 10,000 people will attempt suicide each year. The
      Centre of Excellence in Suicide Prevention in the Capital Region of Denmark is
      treating patients with suicidal behavior, and a recent survey has shown that 30%
      of the patients are suffering from borderline personality disorder. The majority
      of patients (70% to 75%) with borderline personality disorder have a history of
      deliberate self-harm and 10% have a lifetime risk to die by suicide. The DiaS
      trial is comparing dialectical behavior therapy with collaborative assessment and
      management of suicidality-informed supportive psychotherapy, for the risk of
      repetition of deliberate self-harm in patients with a recent suicide attempt and
      personality traits within the spectrum of borderline personality disorder. Both
      treatments have previously shown effects in this group of patients on suicide
      ideation and self-harm compared with treatment as usual. METHODS/DESIGN: The
      trial is designed as a single-center, two-armed, parallel-group observer-blinded
      randomized clinical superiority trial. We will recruit 160 participants with a
      recent suicide attempt and at least two traits of the borderline personality
      disorder from the Centre of Excellence in Suicide Prevention, Capital Region of
      Denmark. Randomization will be performed though a centralized and computer
      generated approach that conceals the randomization sequence. The interventions
      that are offered are a modified version of a dialectical behavior therapy program
      lasting 16 weeks versus collaborative assessment and management of suicidality
      informed supportive psychotherapy, where the duration treatment will vary in
      accordance with established methods up to 16 weeks. The primary outcome measure
      is the ratio of deliberate self-harming acts including suicide attempts measured
      at week 28. Other exploratory outcomes are included such as severity of symptoms,
      suicide intention and ideation, depression, hopelessness, self-esteem,
      impulsivity, anger, and duration of respective treatments. TRIAL REGISTRATION:
      Clinical Trial.gov: NCT01512602.

PMID- 24885905
TI  - In silico modeling of the effects of alpha-synuclein oligomerization on
      dopaminergic neuronal homeostasis.
AB  - BACKGROUND: Alpha-synuclein (ASYN) is central in Parkinson's disease (PD)
      pathogenesis. Converging pieces of evidence suggest that the levels of ASYN
      expression play a critical role in both familial and sporadic Parkinson's
      disease. ASYN fibrils are the main component of inclusions called Lewy Bodies
      (LBs) which are found mainly in the surviving neurons of the substantia nigra.
      Despite the accumulated knowledge regarding the involvement of ASYN in molecular
      mechanisms underlying the development of PD, there is much information missing
      which prevents understanding the causes of the disease and how to stop its
      progression. RESULTS: Using a Systems Biology approach, we develop a biomolecular
      reactions model that describes the intracellular ASYN dynamics in relation to
      overexpression, post-translational modification, oligomerization and degradation
      of the protein. Especially for the proteolysis of ASYN, the model takes into
      account the biological knowledge regarding the contribution of Chaperone Mediated
      Autophagy (CMA), macro-autophagic and proteasome pathways in the protein's
      degradation. Importantly, inhibitory phenomena, caused by ASYN, concerning CMA
      (more specifically the lysosomal-associated membrane protein 2a, abbreviated as
      Lamp2a receptor, which is the rate limiting step of CMA) and the proteasome are
      carefully modeled. The model is validated by simulation studies of known
      experimental overexpression data from SH-SY5Y cells and the unknown model
      parameters are estimated either computationally or by experimental fitting. The
      calibrated model is then tested under three hypothetical intervention scenarios
      and in all cases predicts increased cell viability that agrees with experimental
      evidence. The biomodel has been annotated and is made available in SBML format.
      CONCLUSIONS: The mathematical model presented here successfully simulates the
      dynamic phenomena of ASYN overexpression and oligomerization and predicts the
      biological system's behavior in a number of scenarios not used for model
      calibration. It allows, for the first time, to qualitatively estimate the protein
      levels that are capable of deregulating proteolytic homeostasis. In addition, it
      can help form new hypotheses for intervention that could be tested
      experimentally.

PMID- 24885906
TI  - Stability of gene expression and epigenetic profiles highlights the utility of
      patient-derived paediatric acute lymphoblastic leukaemia xenografts for
      investigating molecular mechanisms of drug resistance.
AB  - BACKGROUND: Patient-derived tumour xenografts are an attractive model for
      preclinical testing of anti-cancer drugs. Insights into tumour biology and
      biomarkers predictive of responses to chemotherapeutic drugs can also be gained
      from investigating xenograft models. As a first step towards examining the
      equivalence of epigenetic profiles between xenografts and primary tumours in
      paediatric leukaemia, we performed genome-scale DNA methylation and gene
      expression profiling on a panel of 10 paediatric B-cell precursor acute
      lymphoblastic leukaemia (BCP-ALL) tumours that were stratified by prednisolone
      response. RESULTS: We found high correlations in DNA methylation and gene
      expression profiles between matching primary and xenograft tumour samples with
      Pearson's correlation coefficients ranging between 0.85 and 0.98. In order to
      demonstrate the potential utility of epigenetic analyses in BCP-ALL xenografts,
      we identified DNA methylation biomarkers that correlated with prednisolone
      responsiveness of the original tumour samples. Differential methylation of CAPS2,
      ARHGAP21, ARX and HOXB6 were confirmed by locus specific analysis. We identified
      20 genes showing an inverse relationship between DNA methylation and gene
      expression in association with prednisolone response. Pathway analysis of these
      genes implicated apoptosis, cell signalling and cell structure networks in
      prednisolone responsiveness. CONCLUSIONS: The findings of this study confirm the
      stability of epigenetic and gene expression profiles of paediatric BCP-ALL
      propagated in mouse xenograft models. Further, our preliminary investigation of
      prednisolone sensitivity highlights the utility of mouse xenograft models for
      preclinical development of novel drug regimens with parallel investigation of
      underlying gene expression and epigenetic responses associated with novel drug
      responses.

PMID- 24885907
TI  - Clinically-relevant consecutive treatment with isoproterenol and adenosine
      protects the failing heart against ischaemia and reperfusion.
AB  - BACKGROUND: Consecutive treatment of normal heart with a high dose of
      isoproterenol and adenosine (Iso/Ade treatment), confers strong protection
      against ischaemia/reperfusion injury. In preparation for translation of this
      cardioprotective strategy into clinical practice during heart surgery, we further
      optimised conditions for this intervention using a clinically-relevant dose of
      Iso and determined its cardioprotective efficacy in hearts isolated from a model
      of surgically-induced heart failure. METHODS: Isolated Langendorff-perfused rat
      hearts were treated sequentially with 5 nM Iso and 30 MUM Ade followed by
      different durations of washout prior to 30 min global ischaemia and 2 hrs
      reperfusion. Reperfusion injury was assessed by measuring haemodynamic function,
      lactate dehydrogenase (LDH) release and infarct size. Protein kinase C (PKC)
      activity and glycogen content were measured in hearts after the treatment. In a
      separate group of hearts, Cyclosporine A (CsA), a mitochondria permeability
      transition pore (MPTP) inhibitor, was added with Iso/Ade. Failing hearts
      extracted after 16 weeks of ligation of left coronary artery in 2 months old rats
      were also subjected to Iso/Ade treatment followed by ischaemia/reperfusion.
      RESULTS: Recovery of the rate pressure product (RPP) in Iso/Ade-treated hearts
      was significantly higher than in controls. Thus in Iso/Ade treated hearts with 5
      nM Iso and no washout period, RPP recovery was 76.3+/-6.9% of initial value vs.
      28.5+/-5.2% in controls. This was associated with a 3 fold reduction in LDH
      release irrespective to the duration of the washout period. Hearts with no
      washout of the drugs (Ade) had least infarct size, highest PKC activity and also
      showed reduced glycogen content. Cardioprotection with CsA was not additive to
      the effect of Iso/Ade treatment. Iso/Ade treatment conferred significant
      protection to failing hearts. Thus, RPP recovery in failing hearts subjected to
      the treatment was 69.0+/-16.3% while in Control hearts 19.7+/-4.0%. LDH release
      in these hearts was also 3 fold lower compared to Control. CONCLUSIONS:
      Consecutive Iso/Ade treatment of normal heart can be effective at clinically
      relevant doses and this effect appears to be mediated by glycogen depletion and
      inhibition of MPTP. This intervention protects clinically relevant failing heart
      model making it a promising candidate for clinical use.

PMID- 24885908
TI  - Changing genetic paradigms: creating next-generation genetic databases as tools
      to understand the emerging complexities of genotype/phenotype relationships.
AB  - Understanding genotype/phenotype relationships has become more complicated as
      increasing amounts of inter- and intra-tissue genetic heterogeneity have been
      revealed through next-generation sequencing and evidence showing that factors
      such as epigenetic modifications, non-coding RNAs and RNA editing can play an
      important role in determining phenotype. Such findings have challenged a number
      of classic genetic assumptions including (i) analysis of genomic sequence
      obtained from blood is an accurate reflection of the genotype responsible for
      phenotype expression in an individual; (ii) that significant genetic alterations
      will be found only in diseased individuals, in germline tissues in inherited
      diseases, or in specific diseased tissues in somatic diseases such as cancer; and
      (iii) that mutation rates in putative disease-associated genes solely determine
      disease phenotypes. With the breakdown of our traditional understanding of
      genotype to phenotype relationships, it is becoming increasingly apparent that
      new analytical tools will be required to determine the relationship between
      genotype and phenotypic expression. To this end, we are proposing that next
      generation genetic database (NGDB) platforms be created that include new
      bioinformatics tools based on algorithms that can evaluate genetic heterogeneity,
      as well as powerful systems biology analysis tools to actively process and
      evaluate the vast amounts of both genomic and genomic-modifying information
      required to reveal the true relationships between genotype and phenotype. 

PMID- 24885909
TI  - Knowledge, attitudes and practices of malaria in Colombia.
AB  - BACKGROUND: Although Colombia has witnessed an important decrease in malaria
      transmission, the disease remains a public health problem with an estimated ~10
      million people currently living in areas with malaria risk and ~61,000 cases
      reported in 2012. This study aimed to determine and compare the level of
      knowledge, attitudes and practices (KAP) about malaria in three endemic
      communities of Colombia to provide the knowledge framework for development of new
      intervention strategies for malaria elimination. METHODS: A cross-sectional KAP
      survey was conducted in the municipalities of Tierralta, Buenaventura and Tumaco,
      categorized according to high risk (HR) and moderate risk (MR) based on the
      annual parasite index (API). Surveys were managed using REDCap and analysed using
      MATLAB and GraphPad Prism. RESULTS: A total of 267 residents, mostly women (74%)
      were surveyed. Although no differences were observed on the knowledge of
      classical malaria symptoms between HR and MR regions, significant differences
      were found in knowledge and attitudes about transmission mechanisms, anti
      malarial use and malaria diagnosis. Most responders in both regions (93.5% in MR,
      and 94.3% in HR areas) indicated use of insecticide-treated nets (ITNs) to
      protect themselves from malaria, and 75.5% of responders in HR indicated they did
      nothing to prevent malaria transmission outdoors. Despite a high level of
      knowledge in the study regions, significant gaps persisted relating to practices.
      Self-medication and poor adherence to treatment, as well as lack of both indoor
      and outdoor vector control measures, were significantly associated with higher
      malaria risk. CONCLUSIONS: Although significant efforts are currently being made
      by the Ministry of Health to use community education as one of the main
      components of the control strategy, these generic education programmes may not be
      applicable to all endemic regions of Colombia given the substantial geographic,
      ethnic and cultural diversity.

PMID- 24885910
TI  - Differences in cationic and anionic charge densities dictate zwitterionic
      associations and stimuli responses.
AB  - Zwitterionic materials have shown their excellent performance in many biological
      and chemical applications. Zwitterionic materials possess moieties that own both
      cationic and anionic groups. The associations among zwitterionic moieties through
      electrostatic interactions play an important role in properties of zwitterionic
      materials. However, the relationship between the molecular structures and
      associations of zwitterionic moieties are still not well understood. This work
      compared thermal- and salt-responsive behaviors of sulfobetaine and
      carboxybetaine polymers by examining their rheological properties as a function
      of temperature and their hydrodynamic sizes as a function of salt concentration.
      Results showed that carboxybetaine polymers do not exhibit stimuli responses as
      expected from the antipolyelectrolyte behavior of zwitterionic polymers as
      observed in sulfobetaine polymers. We studied and compared the associations among
      zwitterionic moieties in these two zwitterionic polymers using molecular dynamic
      simulations. Simulation results show that the charge-density difference between
      cationic and anionic groups determines the associations among zwitterionic
      moieties, which are responsible for different stimuli responses of carboxybetaine
      and sulfobetaine polymers. 

PMID- 24885912
TI  - Physician' entrepreneurship explained: a case study of intra-organizational
      dynamics in Dutch hospitals and specialty clinics.
AB  - BACKGROUND: Challenges brought about by developments such as continuing market
      reforms and budget reductions have strained the relation between managers and
      physicians in hospitals. By applying neo-institutional theory, we research how
      intra-organizational dynamics between physicians and managers induce physicians
      to become entrepreneurs by starting a specialty clinic. In addition, we determine
      the nature of this change by analyzing the intra-organizational dynamics in both
      hospitals and clinics. METHODS: For our research, we interviewed a total of
      fifteen physicians and eight managers in four hospitals and twelve physicians and
      seven managers in twelve specialty clinics. RESULTS: We found evidence that in
      becoming entrepreneurs, physicians are influenced by intra-organizational
      dynamics, including power dependence, interest dissatisfaction, and value
      commitments, between physicians and managers as well as among physicians' groups.
      The precise motivation for starting a new clinic can vary depending on the
      medical or business logic in which the entrepreneurs are embedded, but also the
      presence of an entrepreneurial nature or nurture. Finally we found that the
      entrepreneurial process of starting a specialty clinic is a process of sedimented
      change or hybridized professionalism in which elements of the business logic are
      added to the existing logic of medical professionalism, leading to a hybrid
      logic. CONCLUSIONS: These findings have implications for policy at both the
      national and hospital level. Shared ownership and aligned incentives may provide
      the additional cement in which the developing entrepreneurial values are 'glued'
      to the central medical logic.

PMID- 24885911
TI  - Whole-genome discovery of miRNAs and their targets in wheat (Triticum aestivum
      L.).
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs playing essential roles
      in plant growth, development, and stress responses. Sequencing of small RNAs is a
      starting point for understanding their number, diversity, expression and possible
      roles in plants. RESULTS: In this study, we conducted a genome-wide survey of
      wheat miRNAs from 11 tissues, characterizing a total of 323 novel miRNAs
      belonging to 276 families in wheat. A miRNA conservation analysis identified 191
      wheat-specific miRNAs, 2 monocot-specific miRNAs, and 30 wheat-specific variants
      from 9 highly conserved miRNA families. To understand possible roles of wheat
      miRNAs, we determined 524 potential targets for 124 miRNA families through
      degradome sequencing, and cleavage of a subset of them was validated via 5' RACE.
      Based on the genome-wide identification and characterization of miRNAs and their
      associated target genes, we further identified 64 miRNAs preferentially
      expressing in developing or germinating grains, which could play important roles
      in grain development. CONCLUSION: We discovered 323 wheat novel miRNAs and 524
      target genes for 124 miRNA families in a genome-wide level, and our data will
      serve as a foundation for future research into the functional roles of miRNAs in
      wheat.

PMID- 24885913
TI  - Age at menarche in relation to nutritional status and critical life events among
      rural and urban secondary school girls in post-conflict northern Uganda.
AB  - BACKGROUND: Menarche age is an important indicator of reproductive health of a
      woman or a community. In industrial societies, age at menarche has been declining
      over the last 150 years with a secular trend, and similar trends have been
      reported in some developing countries. Menarche age is affected by genetic and
      environmental cues, including nutrition. The study was designed to determine the
      age at menarche and its relation to childhood critical life events and
      nutritional status in post-conflict northern Uganda. METHODS: This was a
      comparative cross-sectional study of rural and urban secondary school girls in
      northern Uganda. Structured questionnaires were administered to 274 secondary
      school girls, aged 12 - 18 years to determine the age at menarche in relation to
      home location, nutritional status, body composition and critical life events.
      RESULTS: The mean age at menarche was 13.6 +/- 1.3 for rural and 13.3 +/- 1.4
      years for urban dwelling girls (t = -1.996, p = 0.047). Among the body
      composition measures, hip circumference was negatively correlated with the age at
      menarche (r = -0.109, p = 0.036), whereas height, BMI and waist circumference did
      not correlate with menarche. Paternal (but not maternal) education was associated
      with earlier menarche (F = 2.959, p = 0.033). Childhood critical life events were
      not associated with age at menarche. CONCLUSIONS: Age at menarche differed among
      urban and rural dwelling school girls and dependent on current nutritional
      status, as manifested by the hip circumference. It was not associated with
      extreme stressful childhood critical life events.

PMID- 24885914
TI  - Anopheles darlingi (Diptera: Culicidae) displays increased attractiveness to
      infected individuals with Plasmodium vivax gametocytes.
AB  - BACKGROUND: Most hematophagous insects use host odours as chemical cues. The
      odour components, some physiological parameters and host attractiveness are
      affected by several conditions, including infection by parasites, e.g., plasmodia
      and, therefore, change the epidemiological scenario. This study evaluated the
      attractiveness of individuals with vivax malaria before, during (7 days) and
      after treatment (14 days) with specific antimalarial drugs. FINDINGS: Mosquito
      attractiveness to vivax-infected patients was assessed using a vertical
      olfactometer using the foot as a source of body odour. The ratio of Anopheles
      darlingi mosquitoes in the lower chamber of the olfactometer was used to
      calculate the attractiveness, and patient temperature was measured using a
      digital thermometer. An increased attractiveness was found only in patients
      bearing vivax gametocytes during the first experiment (early infection)
      (P<0.001). Patients in the first experiment tended to have a higher body
      temperature, but grouping patients into fever and non-fever resulted in a higher
      attractiveness only in the fever group of gametocyte carriers, suggesting a
      synergistic effect of temperature and gametocytes in the host attractiveness to
      A. darlingi. CONCLUSIONS: Gametocyte presence and fever in vivax malaria patients
      increased short distance host attractiveness to An. darlingi.

PMID- 24885915
TI  - Effectiveness and cost-effectiveness of a group-based pain self-management
      intervention for patients undergoing total hip replacement: feasibility study for
      a randomized controlled trial.
AB  - BACKGROUND: Total hip replacement (THR) is a common elective surgical procedure
      and can be effective for reducing chronic pain. However, waiting times can be
      considerable. A pain self-management intervention may provide patients with
      skills to more effectively manage their pain and its impact during their wait for
      surgery. This study aimed to evaluate the feasibility of conducting a randomized
      controlled trial to assess the effectiveness and cost-effectiveness of a group
      based pain self-management course for patients undergoing THR. METHODS: Patients
      listed for a THR at one orthopedic center were posted a study invitation pack.
      Participants were randomized to attend a pain self-management course plus
      standard care or standard care only. The lay-led course was delivered by
      Arthritis Care and consisted of two half-day sessions prior to surgery and one
      full-day session after surgery. Participants provided outcome and resource-use
      data using a diary and postal questionnaires prior to surgery and one month,
      three months and six months after surgery. Brief telephone interviews were
      conducted with non-participants to explore barriers to participation. RESULTS:
      Invitations were sent to 385 eligible patients and 88 patients (23%) consented to
      participate. Interviews with 57 non-participants revealed the most common reasons
      for non-participation were views about the course and transport difficulties. Of
      the 43 patients randomized to the intervention group, 28 attended the pre
      operative pain self-management sessions and 11 attended the post-operative
      sessions. Participant satisfaction with the course was high, and feedback
      highlighted that patients enjoyed the group format. Retention of participants was
      acceptable (83% of recruited patients completed follow-up) and questionnaire
      return rates were high (72% to 93%), with the exception of the pre-operative
      resource-use diary (35% return rate). Resource-use completion rates allowed for
      an economic evaluation from the health and social care payer perspective.
      CONCLUSIONS: This study highlights the importance of feasibility work prior to a
      randomized controlled trial to assess recruitment methods and rates, barriers to
      participation, logistics of scheduling group-based interventions, acceptability
      of the intervention and piloting resource use questionnaires to improve data
      available for economic evaluations. This information is of value to researchers
      and funders in the design and commissioning of future research. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN52305381.

PMID- 24885916
TI  - A spatial epidemiological analysis of nontuberculous mycobacterial infections in
      Queensland, Australia.
AB  - BACKGROUND: The epidemiology of infections with nontuberculous mycobacteria (NTM)
      has been changing and the incidence has been increasing in some settings. The
      main route of transmission to humans is considered to be from the environment. We
      aimed to describe spatial clusters of cases of NTM infections and to identify
      associated climatic, environmental and socio-economic variables. METHODS: NTM
      data were obtained from the Queensland Mycobacterial Reference Laboratory for the
      period 2001-2011. A Bayesian spatial conditional autoregressive model was
      constructed at the postcode level, with covariates including soil variables,
      maximum, mean and minimum rainfall and temperature, income (proportion of
      population earning < $32,000 and < $52,000) and land use category. RESULTS:
      Significant clusters of NTM infection were identified in the central Queensland
      region overlying the Surat sub-division of the Great Artesian Basin, as well as
      in the lower North Queensland Local Government Area known as the Whitsunday
      region. Our models estimated an expected increase of 21% per percentage increase
      of population earning < $52,000 (95% CI 9-34%) and an expected decrease of 13%
      for every metre increase of average topsoil depth for risk of Mycobacterium
      intracellulare infection (95% CI -3 - -22%). There was an estimated increase of
      79% per mg/m3 increase of soil bulk density (95% CI 26-156%) and 19% decrease for
      every percentage increase in population earning < $32,000 for risk of M. kansasii
      infection (95% CI -3 - -49%). CONCLUSIONS: There were distinct spatial clusters
      of M. kansasii, M. intracellulare and M. abscessus infections in Queensland, and
      a number of socio-ecological, economic and environmental factors were found to be
      associated with NTM infection risk.

PMID- 24885917
TI  - Source attribution of human salmonellosis: an overview of methods and estimates.
AB  - Reducing the burden of foodborne salmonellosis is challenging. It requires
      identification of the most important food sources causing disease and
      prioritization of effective intervention strategies. For this purpose, a variety
      of methods to estimate the relative contribution of different sources of
      Salmonella infections have been applied worldwide. Each has strengths and
      limitations, and the usefulness of each depends on the public health questions
      being addressed. In this study, we reviewed the source attribution methods and
      outcomes of several studies developed in different countries and settings,
      comparing approaches and regional differences in attribution estimates. Reviewed
      results suggest that illnesses and outbreaks are most commonly attributed to
      exposure to contaminated food, and that eggs, broiler chickens, and pigs are
      among the top sources. Although most source attribution studies do not attribute
      salmonellosis to produce, outbreak data in several countries suggest that
      exposure to raw vegetables is also an important source. International travel was
      also a consistently important exposure in several studies. Still, the relative
      contribution of specific sources to human salmonellosis varied substantially
      between studies. Although differences in data inputs, methods, and the point in
      the food system where attribution was estimated contribute to variability between
      studies, observed differences also suggest regional differences in the
      epidemiology of salmonellosis.

PMID- 24885918
TI  - Norovirus-related chronic diarrhea in a patient treated with alemtuzumab for
      chronic lymphocytic leukemia.
AB  - BACKGROUND: Norovirus infection is increasingly recognized as an important cause
      of persistent gastroenteritis in immunocompromised hosts and can be a potential
      cause of morbidity in these populations. CASE PRESENTATION: Here, we report a
      case of norovirus-related chronic diarrhea occurring in a 62-year-old
      immunocompromised patient treated with alemtuzumab for chronic lymphocytic
      leukemia. Despite different therapeutic strategies including tapering of
      immunosuppressive therapy and immunoglobulin administration, diarrhea
      unfortunately did not resolve and lasted for a total of more than twelve weeks
      with prolonged norovirus fecal excretion. CONCLUSIONS: Norovirus infection can
      occur in the setting of alemtuzumab treatment, even as a single agent, and should
      be included in the differential diagnoses of acute and chronic diarrhea in these
      immunocompromised patients. Although the administration of oral immunoglobulin
      has been described as a promising efficient therapy, this was not the case in our
      patient. Clinical trials are thus clearly warranted to better define risk factors
      and efficient therapies for norovirus infection in immunocompromised populations.

PMID- 24885919
TI  - Lin28B expression correlates with aggressive clinicopathological characteristics
      in breast invasive ductal carcinoma.
AB  - Lin28B is a RNA-binding protein that inhibits the let-7 microRNA family and acts
      as an oncogene in various human malignant diseases. Conversely, the members of
      let-7 family function as tumor suppressers and are often inactivated in cancers.
      The interaction of Lin28B/let-7 plays a crucial part of tumorigenesis. In this
      study, the authors examined the Lin28B expression using immunohistochemistry in
      190 breast cancers and analyzed the correlation of Lin28B immunostaining and
      clinicopathological characteristics. Breast cancer patients previously diagnosed
      with invasive ductal carcinomas were enrolled in this study. All cases went
      through surgical procedures as the initial treatment. The characteristics of
      every case were collected, including tumor size, pathologic grade, metastatic
      lymphoid nodes, and estrogen receptor alpha (ERalpha), progesterone receptor
      (PR), and HER2 status. The immunostaining was scored by two independent
      investigators. Eighty-three (43.7%) of 190 cases showed positive expression of
      Lin28B. Lin28B immunostaining was increased in tumors compared with the adjacent
      tissues. Overexpression of Lin28B was linked to poor differentiation, advanced
      stage disease, and Ki67-positive status (all p<0.05). Besides, Lin28B expression
      was significantly different among breast cancer subtypes. This study addresses
      the role of Lin28B in breast cancers and provides insight of its predictive
      effects in disease development.

PMID- 24885920
TI  - microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in
      colorectal cancer.
AB  - BACKGROUND: miR-139-5p was identified to be significantly down-regulated in colon
      tumor tissues by miRNA array. We aimed to clarify its biological function,
      molecular mechanisms and direct target gene in colorectal cancer (CRC). METHODS:
      The biological function of miR-139-5p was examined by cell growth, cell cycle and
      apoptosis analysis in vitro and in vivo. miR-139-5p target gene and signaling
      pathway was identified by luciferase activity assay and western blot. RESULTS:
      miR-139-5p was significantly down-regulated in primary tumor tissues (P <
      0.0001). Ectopic expression of miR-139-5p in colon cancer cell lines
      significantly suppressed cell growth as evidenced by cell viability assay (P <
      0.001) and colony formation assay (P < 0.01) and in xenograft tumor growth in
      nude mice (P < 0.01). miR-139-5p induced apoptosis (P < 0.01), concomitantly with
      up-regulation of key apoptosis genes including cleaved caspase-8, caspase-3,
      caspase-7 and PARP. miR-139-5p also caused cell cycle arrest in G0/G1 phase (P <
      0.01), with upregulation of key G0/G1 phase regulators p21Cip1/Waf1 and p27Kip1.
      Moreover, miR-139-5p inhibited cellular migration (P < 0.001) and invasiveness (P
      < 0.001) through the inhibition of matrix metalloproteinases (MMP)7 and MMP9.
      Oncogene NOTCH1 was revealed to be a putative target of miR-139-5p, which was
      inversely correlated with miR-139-5p expression (r = -0.3862, P = 0.0002).
      CONCLUSIONS: miR-139-5p plays a pivotal role in colon cancer through inhibiting
      cell proliferation, metastasis, and promoting apoptosis and cell cycle arrest by
      targeting oncogenic NOTCH1.

PMID- 24885921
TI  - Variable versus conventional lung protective mechanical ventilation during open
      abdominal surgery: study protocol for a randomized controlled trial.
AB  - BACKGROUND: General anesthesia usually requires mechanical ventilation, which is
      traditionally accomplished with constant tidal volumes in volume- or pressure
      controlled modes. Experimental studies suggest that the use of variable tidal
      volumes (variable ventilation) recruits lung tissue, improves pulmonary function
      and reduces systemic inflammatory response. However, it is currently not known
      whether patients undergoing open abdominal surgery might benefit from
      intraoperative variable ventilation. METHODS/DESIGN: The PROtective VARiable
      ventilation trial ('PROVAR') is a single center, randomized controlled trial
      enrolling 50 patients who are planning for open abdominal surgery expected to
      last longer than 3 hours. PROVAR compares conventional (non-variable) lung
      protective ventilation (CV) with variable lung protective ventilation (VV)
      regarding pulmonary function and inflammatory response. The primary endpoint of
      the study is the forced vital capacity on the first postoperative day. Secondary
      endpoints include further lung function tests, plasma cytokine levels, spatial
      distribution of ventilation assessed by means of electrical impedance tomography
      and postoperative pulmonary complications. DISCUSSION: We hypothesize that VV
      improves lung function and reduces systemic inflammatory response compared to CV
      in patients receiving mechanical ventilation during general anesthesia for open
      abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled
      trial aiming at intra- and postoperative effects of VV on lung function. This
      study may help to define the role of VV during general anesthesia requiring
      mechanical ventilation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01683578
      (registered on September 3 3012).

PMID- 24885923
TI  - Substantially increased sildenafil bioavailability after sublingual
      administration in children with congenital heart disease: two case reports.
AB  - INTRODUCTION: Pulmonary hypertension is a progressive disease of diverse origin
      with devastating consequences in adults as well as in children. The
      phosphodiesterase 5 inhibitor sildenafil successfully lowers pulmonary vascular
      resistance. However, because of its poor enteral absorption, resulting in
      ineffective plasma concentrations, responses in infants and children are often
      erratic. CASE PRESENTATIONS: We report the cases of two Caucasian boys, one born
      at term (case 1) and one aged 2.5 years (case 2), who had structural cardiac and
      pulmonary defects accompanied by symptomatic pulmonary hypertension. They
      received sildenafil enterally and sublingually and also intravenously in one of
      them. Plasma samples were taken at various time points to determine the plasma
      concentrations of sildenafil and its partially active metabolite. Sildenafil and
      N-desmethyl sildenafil were quantified using a validated liquid
      chromatography/mass spectrometry method. Oxygen partial pressure was determined
      from routine arterial blood gas samples. CONCLUSION: In agreement with previous
      observations in adults, we found that sublingual sildenafil was more extensively
      absorbed in our two pediatric patients. After sublingual administration,
      sildenafil plasma concentrations increased by 314% to 361% compared to enteral
      dosing. Concurrently, the metabolic ratio increased, suggesting not only that the
      overall absorption was enhanced but also that first-pass metabolism was partially
      bypassed. In case 2, the free fraction of sildenafil was 0.9%, which is
      considerably less than in adults (4%), suggesting that, in case 2, higher plasma
      concentration would have been needed to achieve effects similar to those in
      adults. Sublingual sildenafil appears to be a promising alternative route of
      administration in children with poor enteral absorption.

PMID- 24885922
TI  - Whole genome profiling of spontaneous and chemically induced mutations in
      Toxoplasma gondii.
AB  - BACKGROUND: Next generation sequencing is helping to overcome limitations in
      organisms less accessible to classical or reverse genetic methods by facilitating
      whole genome mutational analysis studies. One traditionally intractable group,
      the Apicomplexa, contains several important pathogenic protozoan parasites,
      including the Plasmodium species that cause malaria.Here we apply whole genome
      analysis methods to the relatively accessible model apicomplexan, Toxoplasma
      gondii, to optimize forward genetic methods for chemical mutagenesis using N
      ethyl-N-nitrosourea (ENU) and ethylmethane sulfonate (EMS) at varying dosages.
      RESULTS: By comparing three different lab-strains we show that spontaneously
      generated mutations reflect genome composition, without nucleotide bias. However,
      the single nucleotide variations (SNVs) are not distributed randomly over the
      genome; most of these mutations reside either in non-coding sequence or are
      silent with respect to protein coding. This is in contrast to the random genomic
      distribution of mutations induced by chemical mutagenesis. Additionally, we
      report a genome wide transition vs transversion ratio (ti/tv) of 0.91 for
      spontaneous mutations in Toxoplasma, with a slightly higher rate of 1.20 and 1.06
      for variants induced by ENU and EMS respectively. We also show that in the
      Toxoplasma system, surprisingly, both ENU and EMS have a proclivity for inducing
      mutations at A/T base pairs (78.6% and 69.6%, respectively). CONCLUSIONS: The
      number of SNVs between related laboratory strains is relatively low and managed
      by purifying selection away from changes to amino acid sequence. From an
      experimental mutagenesis point of view, both ENU (24.7%) and EMS (29.1%) are more
      likely to generate variation within exons than would naturally accumulate over
      time in culture (19.1%), demonstrating the utility of these approaches for
      yielding proportionally greater changes to the amino acid sequence. These results
      will not only direct the methods of future chemical mutagenesis in Toxoplasma,
      but also aid in designing forward genetic approaches in less accessible
      pathogenic protozoa as well.

PMID- 24885924
TI  - Correlates of objectively measured overweight/obesity and physical activity in
      Kenyan school children: results from ISCOLE-Kenya.
AB  - BACKGROUND: Childhood overweight/obesity and inadequate physical activity burden
      Western countries, and now, pose a growing threat to the health of children in
      low and middle income countries. Behavioural transitions toward more sedentary
      lifestyles coupled with increased consumption of high calorie foods has resulted
      in rising proportions of overweight/obesity and decreasing levels of physical
      activity in school-aged children. The objective of this study was to determine
      the prevalence and to investigate factors associated with overweight/obesity and
      physical activity in Kenyan children aged 9 to 11 years. METHODS: Body
      composition and physical activity measures of participating children were
      accomplished by anthropometric assessment, accelerometry, and administration of
      questionnaires related to diet and lifestyle, and the school and neighbourhood
      environments. Data collection was conducted in the city of Nairobi as part of a
      larger International Study of Childhood Obesity, Lifestyle and Environment.
      RESULTS: A total of 563 participants (46.5% boys, 53.5% girls) were included in
      the analyses. Of these, 3.7% were underweight, 14.4% were overweight, and 6.4%
      were obese based on WHO cut-points. Mean daily sedentary time was 398 minutes,
      time spent in light physical activity was 463 minutes, and time spent in moderate
      to-vigorous physical activity was 36 minutes based on activity cut-points
      developed by Treuth et al. Only 12.6% of participating children were meeting the
      recommendation of >= 60 minutes of daily moderate-to-vigorous physical activity,
      and 45.7% of participants used active transportation to/from school. Increasing
      parental education level, total annual household income, and attending a private
      rather than public school were associated positively with being overweight/obese
      and negatively with meeting physical activity guidelines. CONCLUSIONS: This study
      provided the evidence for an existing prevalence of childhood overweight/obesity
      in Nairobi. Children were spending a considerable amount of time in sedentary and
      light intensity physical activity, with few meeting physical activity guidelines.
      Higher socioeconomic status and parental education attainment were associated
      with a higher likelihood of children being overweight/obese and a lower
      likelihood of children meeting the physical activity recommendations.
      Interventions and strategies should be attentive to the potential health
      consequences of lifestyle transitions resulting from urbanisation and economic
      prosperity.

PMID- 24885925
TI  - Applications of social constructivist learning theories in knowledge translation
      for healthcare professionals: a scoping review.
AB  - BACKGROUND: Use of theory is essential for advancing the science of knowledge
      translation (KT) and for increasing the likelihood that KT interventions will be
      successful in reducing existing research-practice gaps in health care. As a
      sociological theory of knowledge, social constructivist theory may be useful for
      informing the design and evaluation of KT interventions. As such, this scoping
      review explored the extent to which social constructivist theory has been applied
      in the KT literature for healthcare professionals. METHODS: Searches were
      conducted in six databases: Ovid MEDLINE (1948 - May 16, 2011), Ovid EMBASE,
      CINAHL, ERIC, PsycInfo, and AMED. Inclusion criteria were: publications from all
      health professions, research methodologies, as well as conceptual and theoretical
      papers related to KT. To be included in the review, key words such as
      constructivism, social constructivism, or social constructivist theories had to
      be included within the title or abstract. Papers that discussed the use of social
      constructivist theories in the context of undergraduate learning in academic
      settings were excluded from the review. An analytical framework of quantitative
      (numerical) and thematic analysis was used to examine and combine study findings.
      RESULTS: Of the 514 articles screened, 35 papers published between 1992 and 2011
      were deemed eligible and included in the review. This review indicated that use
      of social constructivist theory in the KT literature was limited and haphazard.
      The lack of justification for the use of theory continues to represent a
      shortcoming of the papers reviewed. Potential applications and relevance of
      social constructivist theory in KT in general and in the specific studies were
      not made explicit in most papers. For the acquisition, expression and application
      of knowledge in practice, there was emphasis on how the social constructivist
      theory supports clinicians in expressing this knowledge in their professional
      interactions. CONCLUSIONS: This scoping review was the first to examine use of
      social constructivism in KT studies. While the links between social
      constructivism and KT have not been fully explored, the Knowledge to Action
      framework has strong constructivist underpinnings that can be used in moving
      forward within the broader KT enterprise.

PMID- 24885926
TI  - Myocarditis, pancreatitis, polyarthritis, mononeuritis multiplex and vasculitis
      with symmetrical peripheral gangrene of the lower extremities as a rare
      presentation of leptospirosis: a case report and review of the literature.
AB  - INTRODUCTION: Leptospirosis is a zoonosis caused by the spirochete, Leptospira
      interrogans. While most cases of leptospirosis are mild to moderate, the course
      may be complicated by multiorgan dysfunction. We present a rare case of
      leptospirosis with acute myocarditis, pancreatitis, polyarthritis, mononeuritis
      multiplex and severe vasculitis with necrosis of the extremities. CASE
      PRESENTATION: A 32-year-old man from Congo presented with high-grade fever,
      confusion and headache. He developed tachycardia and hypotension followed by
      electrocardiogram changes and elevation of troponin I levels suggesting
      myocarditis. A physical examination revealed conjunctival suffusion,
      polyarthritis of his lower extremities and cutaneous necrosis of his feet due to
      vasculitis. Laboratory findings included amylase levels 10-fold the upper normal
      serum levels and thrombocytopenia. The diagnosis was confirmed by a positive
      leptospira immunoglobulin M, negative immunoglobulin G and a positive rapid
      agglutination test. Our patient recovered progressively with antimicrobials and
      supportive care. CONCLUSIONS: Because the clinical features and diagnostic
      findings of leptospirosis are not specific, a high index of suspicion must be
      maintained for the diagnosis. Serology is the most important tool for accurate
      and quick diagnosis in order to administer the appropriate therapy.

PMID- 24885927
TI  - Reconstruction and in vivo analysis of the extinct tbx5 gene from ancient
      wingless moa (Aves: Dinornithiformes).
AB  - BACKGROUND: The forelimb-specific gene tbx5 is highly conserved and essential for
      the development of forelimbs in zebrafish, mice, and humans. Amongst birds, a
      single order, Dinornithiformes, comprising the extinct wingless moa of New
      Zealand, are unique in having no skeletal evidence of forelimb-like structures.
      RESULTS: To determine the sequence of tbx5 in moa, we used a range of PCR-based
      techniques on ancient DNA to retrieve all nine tbx5 exons and splice sites from
      the giant moa, Dinornis. Moa Tbx5 is identical to chicken Tbx5 in being able to
      activate the downstream promotors of fgf10 and ANF. In addition we show that
      missexpression of moa tbx5 in the hindlimb of chicken embryos results in the
      formation of forelimb features, suggesting that Tbx5 was fully functional in
      wingless moa. An alternatively spliced exon 1 for tbx5 that is expressed
      specifically in the forelimb region was shown to be almost identical between moa
      and ostrich, suggesting that, as well as being fully functional, tbx5 is likely
      to have been expressed normally in moa since divergence from their flighted
      ancestors, approximately 60 mya. CONCLUSIONS: The results suggests that, as in
      mice, moa tbx5 is necessary for the induction of forelimbs, but is not sufficient
      for their outgrowth. Moa Tbx5 may have played an important role in the
      development of moa's remnant forelimb girdle, and may be required for the
      formation of this structure. Our results further show that genetic changes
      affecting genes other than tbx5 must be responsible for the complete loss of
      forelimbs in moa.

PMID- 24885928
TI  - Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against
      colorectal and pancreatic cancer through inhibition of doublecortin-like kinase
      1.
AB  - BACKGROUND: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor specific
      stem cell marker in colorectal and pancreatic cancer. Previous in vitro and in
      vivo studies have demonstrated the therapeutic effects of inhibiting DCLK1 with
      small interfering RNA (siRNA) as well as genetically targeting the DCLK1+ cell
      for deletion. However, the effects of inhibiting DCLK1 kinase activity have not
      been studied directly. Therefore, we assessed the effects of inhibiting DCLK1
      kinase activity using the novel small molecule kinase inhibitor, LRRK2-IN-1,
      which demonstrates significant affinity for DCLK1. RESULTS: Here we report that
      LRRK2-IN-1 demonstrates potent anti-cancer activity including inhibition of
      cancer cell proliferation, migration, and invasion as well as induction of
      apoptosis and cell cycle arrest. Additionally we found that it regulates
      stemness, epithelial-mesenchymal transition, and oncogenic targets on the
      molecular level. Moreover, we show that LRRK2-IN-1 suppresses DCLK1 kinase
      activity and downstream DCLK1 effector c-MYC, and demonstrate that DCLK1 kinase
      activity is a significant factor in resistance to LRRK2-IN-1. CONCLUSIONS: Given
      DCLK1's tumor stem cell marker status, a strong understanding of its biological
      role and interactions in gastrointestinal tumors may lead to discoveries that
      improve patient outcomes. The results of this study suggest that small molecule
      inhibitors of DCLK1 kinase should be further investigated as they may hold
      promise as anti-tumor stem cell drugs.

PMID- 24885929
TI  - Validation of housekeeping gene and impact on normalized gene expression in clear
      cell renal cell carcinoma: critical reassessment of YBX3/ZONAB/CSDA expression.
AB  - BACKGROUND: YBX3/ZONAB/CSDA is an epithelial-specific transcription factor acting
      in the density-based switch between proliferation and differentiation. Our
      laboratory reported overexpression of YBX3 in clear cell renal cell arcinoma
      (ccRCC), as part of a wide study of YBX3 regulation in vitro and in vivo. The
      preliminary data was limited to 5 cases, of which only 3 could be compared to
      paired normal tissue, and beta-Actin was used as sole reference to normalize gene
      expression. We thus decided to re-evaluate YBX3 expression by real-time-PCR in a
      larger panel of ccRCC samples, and their paired healthy tissue, with special
      attention on experimental biases such as inter-individual variations, primer
      specificity, and reference gene for normalization. RESULTS: Gene expression was
      measured by RT-qPCR in 16 ccRCC samples, each compared to corresponding healthy
      tissue to minimize inter-individual variations. Eight potential housekeeping
      genes were evaluated for expression level and stability among the 16-paired
      samples. Among tested housekeeping genes, PPIA and RPS13, especially in
      combination, proved best suitable to normalize gene expression in ccRCC tissues
      as compared to classical reference genes such as beta-Actin, GAPDH, 18S or B2M.
      Using this pair as reference, YBX3 expression level among a collection of 16
      ccRCC tumors was not significantly increased as compared to normal adjacent
      tissues. However, stratification according to Fuhrman grade disclosed higher YBX3
      expression levels in low-grade tumors and lower in high-grade tumors.
      Immunoperoxidase confirmed homogeneous nuclear staining for YBX3 in low-grade but
      revealed nuclear heterogeneity in high-grade tumors. CONCLUSIONS: This paper
      underlines that special attention to reference gene products in the design of
      real-time PCR analysis of tumoral tissue is crucial to avoid misleading
      conclusions. Furthermore, we found that global YBX3/ZONAB/CSDA mRNA expression
      level may be considered within a "signature" of RCC grading.

PMID- 24885931
TI  - GFF-Ex: a genome feature extraction package.
AB  - BACKGROUND: Genomic features of whole genome sequences emerging from various
      sequencing and annotation projects are represented and stored in several formats.
      Amongst these formats, the GFF (Generic/General Feature Format) has emerged as a
      widely accepted, portable and successfully used flat file format for genome
      annotation storage. With an increasing interest in genome annotation projects and
      secondary and meta-analysis, there is a need for efficient tools to extract
      sequences of interests from GFF files. FINDINGS: We have developed GFF-Ex to
      automate feature-based extraction of sequences from a GFF file. In addition to
      automated sequence extraction of the features described within a feature file,
      GFF-Ex also assigns boundaries for the features (introns, intergenic, regions
      upstream to genes), which are not explicitly specified in the GFF format, and
      exports the corresponding primary sequence information into predefined feature
      specific output files. GFF-Ex package consists of several UNIX Shell and PERL
      scripts. CONCLUSIONS: Compared to other available GFF parsers, GFF-Ex is a
      simpler tool, which permits sequence retrieval based on additional inferred
      features. GFF-Ex can also be integrated with any genome annotation or analysis
      pipeline. GFF-Ex is freely available at http://bioinfo.icgeb.res.in/gff.

PMID- 24885930
TI  - Accumulation of interspersed and sex-specific repeats in the non-recombining
      region of papaya sex chromosomes.
AB  - BACKGROUND: The papaya Y chromosome has undergone a degenerative expansion from
      its ancestral autosome, as a consequence of recombination suppression in the sex
      determining region of the sex chromosomes. The non-recombining feature led to the
      accumulation of repetitive sequences in the male- or hermaphrodite-specific
      regions of the Y or the Yh chromosome (MSY or HSY). Therefore, repeat composition
      and distribution in the sex determining region of papaya sex chromosomes would be
      informative to understand how these repetitive sequences might be involved in the
      early stages of sex chromosome evolution. RESULTS: Detailed composition of
      interspersed, sex-specific, and tandem repeats was analyzed from 8.1 megabases
      (Mb) HSY and 5.3 Mb corresponding X chromosomal regions. Approximately 77% of the
      HSY and 64% of the corresponding X region were occupied by repetitive sequences.
      Ty3-gypsy retrotransposons were the most abundant interspersed repeats in both
      regions. Comparative analysis of repetitive sequences between the sex determining
      region of papaya X chromosome and orthologous autosomal sequences of Vasconcellea
      monoica, a close relative of papaya lacking sex chromosomes, revealed distinctive
      differences in the accumulation of Ty3-Gypsy, suggesting that the evolution of
      the papaya sex determining region may accompany Ty3-Gypsy element accumulation.
      In total, 21 sex-specific repeats were identified from the sex determining
      region; 20 from the HSY and one from the X. Interestingly, most HSY-specific
      repeats were detected in two regions where the HSY expansion occurred, suggesting
      that the HSY expansion may result in the accumulation of sex-specific repeats or
      that HSY-specific repeats might play an important role in the HSY expansion. The
      analysis of simple sequence repeats (SSRs) revealed that longer SSRs were less
      abundant in the papaya sex determining region than the other chromosomal regions.
      CONCLUSION: Major repetitive elements were Ty3-gypsy retrotransposons in both the
      HSY and the corresponding X. Accumulation of Ty3-Gypsy retrotransposons in the
      sex determining region of papaya X chromosome was significantly higher than that
      in the corresponding region of V. monoica, suggesting that Ty3-Gypsy could be
      crucial for the expansion and evolution of the sex determining region in papaya.
      Most sex-specific repeats were located in the two HSY expansion regions.

PMID- 24885932
TI  - Interaction of light regimes and circadian clocks modulate timing of pre-adult
      developmental events in Drosophila.
AB  - BACKGROUND: Circadian clocks have been postulated to regulate development time in
      several species of insects including fruit flies Drosophila melanogaster.
      Previously we have reported that selection for faster pre-adult development
      reduces development time (by ~19 h or ~11%) and clock period (by ~0.5 h),
      suggesting a role of circadian clocks in the regulation of development time in D.
      melanogaster. We reasoned that these faster developing flies could serve as a
      model to study stage-specific interaction of circadian clocks and developmental
      events with the environmental light/dark (LD) conditions. We assayed the duration
      of three pre-adult stages in the faster developing (FD) and control (BD)
      populations under a variety of light regimes that are known to modulate circadian
      clocks and pre-adult development time of Drosophila to examine the role of
      circadian clocks in the timing of pre-adult developmental stages. RESULTS: We
      find that the duration of pre-adult stages was shorter under constant light (LL)
      and short period light (L)/dark (D) cycles (L:D = 10:10 h; T20) compared to the
      standard 24 h day (L:D = 12:12 h; T24), long LD cycles (L:D = 14:14 h; T28) and
      constant darkness (DD). The difference in the duration of pre-adult stages
      between the FD and BD populations was significantly smaller under the three LD
      cycles and LL compared to DD, possibly due to the fact that clocks of both FD and
      BD flies are driven at the same pace in the three LD regimes owing to circadian
      entrainment, or are rendered dysfunctional under LL. CONCLUSIONS: These results
      suggest that interaction between light regimes and circadian clocks regulate the
      duration of pre-adult developmental stages in fruit flies D. melanogaster.

PMID- 24885934
TI  - Self-assembly of phosphate amphiphiles in mixtures of prebiotically plausible
      surfactants.
AB  - The spontaneous formation of closed bilayer structures from prebiotically
      plausible amphiphiles is an essential requirement for the emergence of early
      cells on prebiotic Earth. The sources of amphiphiles could have been both endo-
      and exogenous (accretion of meteorite carbonaceous material or interstellar dust
      particles). Among all prebiotic possible amphiphile candidates, those containing
      phosphate are the least investigated species because their self-assembly occurs
      in a seemingly too narrow range of conditions. The self-assembly of simple
      phosphate amphiphiles should, however, be of great interest, as contemporary
      membranes predominantly contain phospholipids. In contrast to common
      expectations, we show that these amphiphiles can be easily synthesized under
      prebiotically plausible environmental conditions and can efficiently form bilayer
      structures in the presence of various co-surfactants across a large range of pH
      values. Vesiculation was even observed in crude reaction mixtures that contained
      1-decanol as the amphiphile precursor. The two best co-surfactants promoted
      vesicle formation over the entire pH range in aqueous solutions. Expanding the pH
      range where bilayer membranes self-assemble and remain intact is a prerequisite
      for the emergence of early cell-like compartments and their preservation under
      fluctuating environmental conditions. These mixed bilayers also retained small
      charged solutes, such as dyes. These results demonstrate that alkyl phosphate
      amphiphiles might have played a significant role as early compartment building
      blocks.

PMID- 24885935
TI  - Evaluation of liver parenchyma and perfusion using dynamic contrast-enhanced
      computed tomography and contrast-enhanced ultrasonography in captive green
      iguanas (Iguana iguana) under general anesthesia.
AB  - BACKGROUND: Contrast-enhanced diagnostic imaging techniques are considered useful
      in veterinary and human medicine to evaluate liver perfusion and focal hepatic
      lesions. Although hepatic diseases are a common occurrence in reptile medicine,
      there is no reference to the use of contrast-enhanced ultrasound (CEUS) and
      contrast-enhanced computed tomography (CECT) to evaluate the liver in lizards.
      Therefore, the aim of this study was to evaluate the pattern of change in
      echogenicity and attenuation of the liver in green iguanas (Iguana iguana) after
      administration of specific contrast media. RESULTS: An increase in liver
      echogenicity and density was evident during CEUS and CECT, respectively. In CEUS,
      the mean +/- SD (median; range) peak enhancement was 19.9% +/- 7.5 (18.3; 11.7
      34.6). Time to peak enhancement was 134.0 +/- 125.1 (68.4; 59.6-364.5) seconds.
      During CECT, first visualization of the contrast medium was at 3.6 +/- 0.5 (4; 3
      4) seconds in the aorta, 10.7 +/- 2.2 (10.5; 7-14) seconds in the hepatic
      arteries, and 15 +/- 4.5 (14.5; 10-24) seconds in the liver parenchyma. Time to
      peak was 14.1 +/- 3.4 (13; 11-21) and 31 +/- 9.6 (29; 23-45) seconds in the aorta
      and the liver parenchyma, respectively. CONCLUSION: CEUS and dynamic CECT are
      practical means to determine liver hemodynamics in green iguanas. Distribution of
      contrast medium in iguana differed from mammals. Specific reference ranges of
      hepatic perfusion for diagnostic evaluation of the liver in iguanas are necessary
      since the use of mammalian references may lead the clinician to formulate
      incorrect diagnostic suspicions.

PMID- 24885936
TI  - Colorimetric Detection of Sulfite in Foods by a TMB-O2-Co3O4 Nanoparticles
      Detection System.
AB  - In this paper, we first discovered that Co3O4 nanoparticles (NPs) possess
      intrinsic oxidase-like activity and can catalytically oxidize peroxidase
      substrates, such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
      diammonium salt (ABTS) and 3,3',5,5'-tetramethylbenzidine (TMB), to form colored
      products, in the absence of exogenously added H2O2. The presence of sulfite
      inhibited the TMB-O2-Co3O4 NPs reaction system and caused a change in color of
      the reaction system. On the basis of this phenomenon, a colormetric approach to
      detect sulfite was established with a good linear relationship ranging from
      0.2*10(-6) to 1.6*10(-5) M and a detection limit of 5.3*10(-8) M. The method was
      used to detect sulfite in foods. Good recoveries ranging from 93.8% to 100.5%
      were obtained. Furthermore, the mechanism was studied and results showed that the
      oxidase-like activity of the Co3O4 NPs was not from *OH or O2*- radical
      generated. It may probably originate from their ability to transfer an electron
      between the peroxidase substrate and oxygen absorbed on the surface of the Co3O4
      NPs.

PMID- 24885933
TI  - Towards the clinical implementation of pharmacogenetics in bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BD) is a psychiatric illness defined by
      pathological alterations between the mood states of mania and depression, causing
      disability, imposing healthcare costs and elevating the risk of suicide. Although
      effective treatments for BD exist, variability in outcomes leads to a large
      number of treatment failures, typically followed by a trial and error process of
      medication switches that can take years. Pharmacogenetic testing (PGT), by
      tailoring drug choice to an individual, may personalize and expedite treatment so
      as to identify more rapidly medications well suited to individual BD patients.
      DISCUSSION: A number of associations have been made in BD between medication
      response phenotypes and specific genetic markers. However, to date clinical
      adoption of PGT has been limited, often citing questions that must be answered
      before it can be widely utilized. These include: What are the requirements of
      supporting evidence? How large is a clinically relevant effect? What degree of
      specificity and sensitivity are required? Does a given marker influence decision
      making and have clinical utility? In many cases, the answers to these questions
      remain unknown, and ultimately, the question of whether PGT is valid and useful
      must be determined empirically. Towards this aim, we have reviewed the literature
      and selected drug-genotype associations with the strongest evidence for utility
      in BD. SUMMARY: Based upon these findings, we propose a preliminary panel for use
      in PGT, and a method by which the results of a PGT panel can be integrated for
      clinical interpretation. Finally, we argue that based on the sufficiency of
      accumulated evidence, PGT implementation studies are now warranted. We propose
      and discuss the design for a randomized clinical trial to test the use of PGT in
      the treatment of BD.

PMID- 24885937
TI  - Quantitative ethnomedicinal study of plants used in the skardu valley at high
      altitude of Karakoram-Himalayan range, Pakistan.
AB  - BACKGROUND: The tribal inhabitants of the Skardu valley (Pakistan) live in an
      area of great endemic botanic diversity. This paper presents the first
      quantitative ethnomedicinal spectrum of the valley and information on the uses of
      medicinal plant. This paper aims to analyze and catalogue such knowledge based on
      Relative Frequency Citation (RFC) and Use Value (UV) of medicinal plants in
      addition to the configuration of the Pearson correlation coefficient. METHODS:
      The field study was carried out over a period of approximately 2 years (2011
      2013) using semi-structured interviews with 71 informants (most of the informants
      belonged to an age between 50 and 70 years) in six remote locations in the
      valley. Ethnomedicinal data was analyzed using frequency citation (FC), relative
      frequency of citation (RFC) and use value (UV) along with a Pearson correlation
      coefficient (PCC). Demographic characteristics of participants, ethnobotanical
      inventory of plants and data on medicinal application and administration were
      recorded. RESULTS: A total of 50 medicinal plants belonging to 25 families were
      reported to be used against 33 different ailments in the valley. The maximum
      reported medicinal plant families were Asteraceae (7 report species), Lamiaceae
      (6) , Polygonaceae (4) and Rosaceae (4), the most dominant life form of the
      species includes herbs (38) followed by shrubs and subshrubs (12), the most
      frequent used part was leaves (41%) followed by root (26%), flower (14%), fruit
      (9%), seeds (8%), bulb (1%) and bark (1%), the most common preparation and
      administration methods were infusion (32%), decoction (26%), paste (18%), herbal
      juice (17%) and powder drug (7%). The Pearson correlation coefficient between RFC
      and UV was 0.732 showing highly positive significant association. CONCLUSIONS: In
      this study, we have documented considerable indigenous knowledge about the native
      medicinal plants in Skardu valley for treating common ailments which are ready to
      be further investigated phytochemically and pharmacologically which leads to
      natural drug discovery development. The study has various socioeconomic
      dimensions which are associated with the local communities.

PMID- 24885938
TI  - One year survival of ART and conventional restorations in patients with
      disability.
AB  - BACKGROUND: Providing restorative treatment for persons with disability may be
      challenging and has been related to the patient's ability to cope with the
      anxiety engendered by treatment and to cooperate fully with the demands of the
      clinical situation. The aim of the present study was to assess the survival rate
      of ART restorations compared to conventional restorations in people with
      disability referred for special care dentistry. METHODS: Three treatment
      protocols were distinguished: ART (hand instruments/high-viscosity glass
      ionomer); conventional restorative treatment (rotary instrumentation/resin
      composite) in the clinic (CRT/clinic) and under general anaesthesia (CRT/GA).
      Patients were referred for restorative care to a special care centre and treated
      by one of two specialists. Patients and/or their caregivers were provided with
      written and verbal information regarding the proposed techniques, and selected
      the type of treatment they were to receive. Treatment was provided as selected
      but if this option proved clinically unfeasible one of the alternative techniques
      was subsequently proposed. Evaluation of restoration survival was performed by
      two independent trained and calibrated examiners using established ART
      restoration assessment codes at 6 months and 12 months. The Proportional Hazard
      model with frailty corrections was applied to calculate survival estimates over a
      one year period. RESULTS: 66 patients (13.6 +/- 7.8 years) with 16 different
      medical disorders participated. CRT/clinic proved feasible for 5 patients (7.5%),
      the ART approach for 47 patients (71.2%), and 14 patients received CRT/GA
      (21.2%). In all, 298 dentine carious lesions were restored in primary and
      permanent teeth, 182 (ART), 21 (CRT/clinic) and 95 (CRT/GA). The 1-year survival
      rates and jackknife standard error of ART and CRT restorations were 97.8 +/- 1.0%
      and 90.5 +/- 3.2%, respectively (p = 0.01). CONCLUSIONS: These short-term results
      indicate that ART appears to be an effective treatment protocol for treating
      patients with disability restoratively, many of whom have difficulty coping with
      the conventional restorative treatment. TRIAL REGISTRATION NUMBER: Netherlands
      Trial Registration: NTR 4400.

PMID- 24885939
TI  - Duration of exclusive breastfeeding in a Brazilian population: new determinants
      in a cohort study.
AB  - BACKGROUND: Determinants of the duration of exclusive breastfeeding (EBF) differ
      in effect and magnitude across populations. The present study aimed to identify
      factors associated with discontinuation of EBF in a municipality in northeastern
      Brazil, including variables that have received little or no attention in previous
      literature. METHODS: This cohort study involved 1,344 mother-child pairs selected
      from maternity hospitals in Feira de Santana, Bahia, Brazil. Subjects were
      followed up for 6 months through monthly home visits, and discontinuation of EBF
      was recorded. Possible determinants were tested using Cox's four-level
      hierarchical survival model, taking into consideration the temporal proximity of
      the predisposing factors to interruption of EBF. Median duration of EBF was
      estimated using Kaplan-Meier's survival curve. RESULTS: Median duration of EBF
      was 89 days. Out of the 19 variables tested, 9 showed an association with EBF
      cessation; of these, two had never been evaluated in Brazilian studies, namely,
      mother partner's appreciation for breastfeeding (hazard ratio [HR] 0.62; 95%
      confidence interval [95% CI] 0.48-0.79) and limiting the number of nighttime
      feeds at the breast (HR 1.58; 95% CI 1.11-2.23). Another two variables that had
      been previously evaluated, but had never been described as determinants of
      discontinuation of EBF showed association: presence of cracked nipples (HR 2.54;
      95% CI 2.06-3.13) and prenatal care provided by public services (HR 1.34; 95% CI
      1.17-1.55). Other variables showing associations with the outcome were: guidance
      on breastfeeding received at the hospital (HR 0.80; 95% CI 0.68-0.92), birth in a
      Baby-Friendly Hospital (HR 0.85; 95% CI 0.73-0.99), less than or equal to 8 years
      of maternal schooling (HR 1.34, 95% CI 1.17-1.53), mother working outside the
      home (HR 1.73; 95% CI 1.53-1.95), and use of a pacifier (HR 1.40; 95% CI 1.14
      1.71). CONCLUSIONS: The study confirmed that the factors associated with EBF
      duration are multiple, variable, and dependent on the population being evaluated.
      Characteristics that had never been previously evaluated or described, at least
      in Brazilian studies, behaved as determinants of EBF in the present study, and
      thus allow to expand the existing list of factors determining this practice.

PMID- 24885940
TI  - Wide-neck renal artery aneurysm: parenchymal sparing endovascular treatment with
      a new device.
AB  - BACKGROUND: Renal artery aneurysm is a rare disorder with a high mortality rate
      in the event of rupture, the most frequent complication, which can also occur in
      lesions smaller than those indicated for treatment by current criteria. Surgery
      is still the first-line treatment, although a growing trend toward endovascular
      management of visceral artery aneurysms has emerged because of the high efficacy
      and low invasiveness that has been demonstrated by several authors. Treatment of
      wide-necked aneurysms and, depending on location, those at renal artery
      bifurcations or distal branches is more complex and may require invasive surgical
      techniques, such as bench surgery. CASE PRESENTATION: We describe the successful
      use of a new neurointerventional coil to treat an enlarging wide-necked segmental
      branch renal aneurysm in an elderly woman who was not a candidate for surgery
      because of several comorbidities. CONCLUSIONS: The technique described allowed
      safe, successful treatment of a wide-necked aneurysm in an unfavorable vascular
      territory, reducing the risk of downstream artery embolization and consequent
      parenchymal damage and decreased renal function. In similar cases, other
      endovascular devices have often proven to be ineffective at nephron sparing. To
      validate the safety and efficacy of this system, more cases treated in this
      manner should be studied.

PMID- 24885941
TI  - Multi-country willingness to pay study on road-traffic environmental health
      effects: are people willing and able to provide a number?
AB  - BACKGROUND: The health impacts from traffic-related pollutants bring costs to
      society, which are often not reflected in market prices for transportation. We
      set out to simultaneously assess the willingness-to-pay (WTP) for traffic-related
      air pollution and noise effect on health, using a single measurement instrument
      and approach. We investigated the proportion and determinants of "protest vote/PV
      responses (people who were against valuing their health in terms of money)" and
      "don't know"/DK answers, and explored the effect of DK on the WTP distributions.
      METHODS: Within the framework of the EU-funded project INTARESE, we asked over
      5,200 respondents in five European countries to state their WTP to avoid health
      effects from road traffic-related air pollution and noise in an open-ended web
      based questionnaire. Determinants of PV and DK were studied by logistic
      regression using variables concerning socio-demographics, income, health and
      environmental concern, and risk perception. RESULTS: About 10% of the respondents
      indicated a PV response and between 47-56% of respondents gave DK responses.
      About one-third of PV respondents thought that costs should be included in
      transportation prices, i.e. the polluter should pay. Logistic regression analyses
      showed associations of PV and DK with several factors. In addition to social
      demographic, economic and health factors known to affect WTP, environmental
      concern, awareness of health effects, respondent's ability to relax in polluted
      places, and their view on the government's role to reduce pollution and on policy
      to improve wellbeing, also affected the PV and DK response. An exploratory
      weighting and imputation exercise did not show substantial effects of DK on the
      WTP distribution. CONCLUSIONS: With a proportion of about 50%, DK answers may be
      a more relevant issue affecting WTP than PV's. The likelihood to give PV and DK
      response were influenced by socio-demographic, economic and health factors, as
      well as environmental concerns and appreciation of environmental conditions and
      policies. In contested policy issues where actual policy may be based on WTP
      studies, PV and DK answers may indeed affect the outcome of the WTP study. PV and
      DK answers and their determinants therefore deserve further study in CV studies
      on environmental health effects.

PMID- 24885942
TI  - Changes in fibroblast growth factor 23 levels in normophosphatemic patients with
      chronic kidney disease stage 3 treated with lanthanum carbonate: results of the
      PREFECT study, a phase 2a, double blind, randomized, placebo-controlled trial.
AB  - BACKGROUND: High levels of circulating fibroblast growth factor 23 (FGF23) are
      associated with chronic kidney disease (CKD) progression and high mortality. In
      the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment (PREFECT)
      study, we assessed the effect of reducing intestinal phosphate absorption using
      lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage
      3. METHODS: Thirty-five individuals were randomized to lanthanum carbonate 3000
      mg/day (n=23) or placebo (n=12) for 12 weeks. Levels of intact FGF23 (iFGF23), C
      terminal FGF23, serum and urinary phosphate and calcium, intact parathyroid
      hormone and 1,25-dihydroxyvitamin D were assessed. RESULTS: The median age was 65
      years in the lanthanum group and 73 years in the placebo group; 58.8% and 41.7%
      were men, respectively. No significant difference was seen in mean iFGF23 between
      groups at week 12. There was, however, a transient reduction from baseline in
      iFGF23 in the lanthanum group at week 1, from 70.5 pg/ml to 51.9 pg/ml, which was
      not seen in the placebo group; this between-group difference in percentage change
      from baseline was significant in post hoc analyses (p=0.0102). Urinary phosphate
      decreased after 1 week of lanthanum treatment and remained low at week 12.
      CONCLUSIONS: Reducing intestinal phosphate absorption with lanthanum carbonate
      did not lead to sustained reductions in iFGF23 in patients with CKD stage 3,
      although phosphaturia decreased. This suggests that factors other than phosphate
      burden may be responsible for driving increases in circulating FGF23 in patients
      with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01128179, 20 May 2010.

PMID- 24885943
TI  - Impact of clinical experience on type V pit pattern analysis using magnifying
      chromoendoscopy in early colorectal cancer: a cross-sectional interpretation
      test.
AB  - BACKGROUND: Although type V pit pattern analysis is effective in determining the
      invasion depth of early colorectal cancers, the clinical results may vary because
      findings are operator-dependent. This study aimed to assess the benefits of type
      V pit pattern analysis in estimating the invasion depth using magnifying
      chromoendoscopy compared to that with conventional colonoscopy. METHODS: A cross
      sectional interpretation test involving 32 endoscopists with varying levels of
      experience performing colonoscopies was conducted. Fifty histopathologically
      diagnosed cases of intramucosal or submucosal cancer were selected
      retrospectively. The lesions were classified as superficial or deep by the
      endoscopists, based on magnifying chromoendoscopic and non-magnifying endoscopic
      images. The endoscopists were classified into 3 groups based on the number of
      colonoscopies performed: I (<500), II (501-5000), and III (>5000). Differences in
      the interpretation of invasion depth between group III and groups I and II were
      assessed using the Mann-Whitney U test. RESULTS: There was no significant
      difference in the median number of correct interpretations using non-magnifying
      endoscopic images among the groups. However, a significant difference (P = 0.007)
      was observed between the results of groups III and I when the analysis was
      performed using magnifying chromoendoscopic images. CONCLUSIONS: When performed
      by less experienced endoscopists, pit pattern analysis of colonic lesions using
      magnifying chromoendoscopy is not a reliable modality for estimating invasion
      depth in early colorectal cancer.

PMID- 24885944
TI  - TrackArt: the user friendly interface for single molecule tracking data analysis
      and simulation applied to complex diffusion in mica supported lipid bilayers.
AB  - BACKGROUND: Single molecule tracking (SMT) analysis of fluorescently tagged lipid
      and protein probes is an attractive alternative to ensemble averaged methods such
      as fluorescence correlation spectroscopy (FCS) or fluorescence recovery after
      photobleaching (FRAP) for measuring diffusion in artificial and plasma membranes.
      The meaningful estimation of diffusion coefficients and their errors is however
      not straightforward, and is heavily dependent on sample type, acquisition method,
      and equipment used. Many approaches require advanced computing and programming
      skills for their implementation. FINDINGS: Here we present TrackArt software, an
      accessible graphic interface for simulation and complex analysis of multiple
      particle paths. Imported trajectories can be filtered to eliminate spurious or
      corrupted tracks, and are then analyzed using several previously described
      methodologies, to yield single or multiple diffusion coefficients, their
      population fractions, and estimated errors. We use TrackArt to analyze the single
      molecule diffusion behavior of a sphingolipid analog SM-Atto647N, in mica
      supported DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) bilayers. Fitting with
      a two-component diffusion model confirms the existence of two separate
      populations of diffusing particles in these bilayers on mica. As a demonstration
      of the TrackArt workflow, we characterize and discuss the effective activation
      energies required to increase the diffusion rates of these populations, obtained
      from Arrhenius plots of temperature-dependent diffusion. Finally, TrackArt
      provides a simulation module, allowing the user to generate models with multiple
      particle trajectories, diffusing with different characteristics. Maps of domains,
      acting as impermeable or permeable obstacles for particles diffusing with given
      rate constants and diffusion coefficients, can be simulated or imported from an
      image. Importantly, this allows one to use simulated data with a known diffusion
      behavior as a comparison for results acquired using particular algorithms on
      actual, "natural" samples whose diffusion behavior is to be extracted. It can
      also serve as a tool for demonstrating diffusion principles. CONCLUSIONS:
      TrackArt is an open source, platform-independent, Matlab-based graphical user
      interface, and is easy to use even for those unfamiliar with the Matlab
      programming environment. TrackArt can be used for accurate simulation and
      analysis of complex diffusion data, such as diffusion in lipid bilayers,
      providing publication-quality formatted results.

PMID- 24885945
TI  - Body composition and physical activity in Italian university students.
AB  - BACKGROUND: Increased sedentary lifestyle and prevalence of overweight/obesity
      are common in western countries. The purposes of this study were (i) to assess
      the main health-related anthropometric characteristics in a sample of students in
      relation to sex, amount of physical activity and sport discipline, and (ii) to
      investigate the accuracy of the Body Mass Index (BMI) and Waist-to-Stature Ratio
      (WSR) as indicators of body fat percentage (%F) in young adults. METHODS: 734
      university students, both sexes, participated in the present research. A self
      administered questionnaire acquired socio-demographic information (sex, age) and
      sport participation (hours/week, sport discipline). Anthropometric measurements
      and grip strength values were acquired according to standardized procedures. Body
      composition was assessed by means of the skinfold method. RESULTS: Most students
      had normal BMI, WSR and %F. There were significant statistical differences in all
      anthropometric traits between the two sexes. One-way ANOVAs within sex showed
      statistically significant differences in biceps skinfold, waist circumference
      (WC), WSR, body density (BD), %F and fat mass (FM) among different levels of
      physical activity in males; and in weight, BMI, arm girths and fat free mass
      (FFM) in females. One-way ANOVAs within sex showed statistically significant
      differences in arm girths, grip strength and FFM among different sport
      disciplines in males, and in height, weight, BMI, WC, relaxed arm girth, grip
      strength, FM and FFM in females. Despite the significant and positive correlation
      of BMI and WSR with %F both indices had poor sensitivity. CONCLUSIONS: Physical
      activity plays an important role in body composition parameters: the most active
      males had the least amount of FM and the most active females had the greatest
      amount of FFM. BMI and WSR are not accurate indices of adiposity in young adults.

PMID- 24885946
TI  - Ginger extract diminishes chronic fructose consumption-induced kidney injury
      through suppression of renal overexpression of proinflammatory cytokines in rats.
AB  - BACKGROUND: The metabolic syndrome is associated with an increased risk of
      development and progression of chronic kidney disease. Renal inflammation is well
      known to play an important role in the initiation and progression of
      tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used
      spices and medicinal plants, has been demonstrated to improve diet-induced
      metabolic abnormalities. However, the efficacy of ginger on the metabolic
      syndrome-associated kidney injury remains unknown. This study aimed to
      investigate the impact of ginger on fructose consumption-induced adverse effects
      in the kidneys. METHODS: The fructose control rats were treated with 10% fructose
      in drinking water over 5 weeks. The fructose consumption in ginger-treated rats
      was adjusted to match that of fructose control group. The ethanolic extract of
      ginger was co-administered (once daily by oral gavage). The indexes of lipid and
      glucose homeostasis were determined enzymatically, by ELISA and/or
      histologically. Gene expression was analyzed by Real-Time PCR. RESULTS: In
      addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with
      ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as
      characterized by focal cast formation, slough and dilation of tubular epithelial
      cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished
      excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene
      expression profiles revealed that ginger suppressed fructose-stimulated monocyte
      chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In
      accord, overexpression of two important macrophage accumulation markers CD68 and
      F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha,
      interleukin-6, transforming growth factor-beta1 and plasminogen activator
      inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the
      downregulated ratio of urokinase-type plasminogen activator to PAI-1.
      CONCLUSIONS: The present results suggest that ginger supplement diminishes
      fructose-induced kidney injury through suppression of renal overexpression of
      macrophage-associated proinflammatory cytokines in rats. Our findings provide
      evidence supporting the protective effect of ginger on the metabolic syndrome
      associated kidney injury.

PMID- 24885947
TI  - Both radical prostatectomy following treatment with neoadjuvant LHRH agonist and
      estramustine and radiotherapy following treatment with neoadjuvant hormonal
      therapy achieved favorable oncological outcome in high-risk prostate cancer: a
      propensity-score matching analysis.
AB  - BACKGROUND: To date, the different treatment modalities for high-risk prostate
      cancer (Pca) have not been compared in any sufficiently large-scale, prospective,
      randomized clinical trial. We used propensity-score matching analysis to compare
      the oncological outcomes of high-risk prostate cancer between patients treated
      with radical prostatectomy (RP) and those treated with radiation therapy (RT).
      METHODS: We studied 216 patients who received neoadjuvant therapy followed by RP
      (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy
      (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone
      releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months
      prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a
      3-dimensional conformal radiotherapy technique. The total radiation dose was 70
      to 76 Gy administered at 2 Gy/fraction. RESULTS: Propensity-score matching
      identified 78 matched pairs of patients. The 3-year overall survival rates were
      98.3% and 92.1% in the RP and RT groups, respectively (P=0.156). The 3-year
      biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT
      groups, respectively (P=0.878). CONCLUSIONS: Our study findings may suggest
      almost identical cancer control of RP and RT with appropriate neoadjuvant therapy
      in high-risk Pca. Therefore, issues of health-related quality of life may have an
      important impact on decision making in treatment of high-risk Pca.

PMID- 24885949
TI  - Hombre Seguro (Safe Men): a sexual risk reduction intervention for male clients
      of female sex workers.
AB  - BACKGROUND: Male clients of female sex workers (FSWs) are at risk of HIV and
      other sexually transmitted infections (STIs). We conducted a two-arm randomized
      controlled trial to test the efficacy of a sexual risk reduction intervention for
      male clients of FSWs in Tijuana, Mexico. METHODS/DESIGN: Male clients of FSWs who
      were at least 18, were HIV-negative at baseline, and reported recent unprotected
      sex with FSWs were randomized to the Hombre Seguro sexual risk reduction
      intervention, or a time-attention didactic control condition. Each condition
      lasted approximately one hour. Participants underwent interviewer-administered
      surveys and testing for HIV and other STIs at baseline, and at 4, 8, and 12 month
      follow-ups. Combined HIV/STI incidence and unprotected vaginal and anal sex acts
      with FSWs were the primary outcomes. DISCUSSION: A total of 400 participants were
      randomized to one of the two conditions. Analyses indicated that randomization
      was successful; there were no significant differences between the participants in
      the two conditions at baseline. Average follow-up was 84% across both conditions.
      This is the first study to test the efficacy of a sexual risk reduction
      intervention for male clients of FSWs using the rigor of a randomized controlled
      trial. TRIAL REGISTRATION: NCT01280838, Date of registration: January 19, 2011.

PMID- 24885948
TI  - Multikinase inhibitor sorafenib prevents pressure overload-induced left
      ventricular hypertrophy in rats by blocking the c-Raf/ERK1/2 signaling pathway.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is a potent risk factor for sudden
      death and congestive heart failure. METHODS: We tested the effect of sorafenib, a
      multikinase inhibitor (10 mg/kg, given orally, starting 2 days prior to banding,
      till sacrifice on day 14), on the development of LVH following aortic banding in
      rats. RESULTS: The latter resulted in significant LVH caused by both an increase
      in cardiomyocyte volume and interstitial collagen deposition. The observed LVH
      was entirely blocked by sorafenib downregulating both of these components. LVH
      was associated with PDGF-BB and TGFbeta1 overexpression, as well as
      phosphorylation of c-raf and ERK1/2. Additionally, the transcription factors c
      myc and c-fos leading to proliferation as well as the hypertrophy-inducing
      transcription factor GATA4 and its regulated gene ANP were all upregulated in
      response to aortic banding. All these overexpressions and upregulations were
      inhibited upon sorafenib treatment. CONCLUSION: We show that sorafenib exhibits a
      regulatory role on the occurrence of LVH following AB in rats by blocking the
      rise in growth factors PDGF-BB and TGFbeta1, activation of the corresponding c
      Raf-ERK1/2 signaling pathway and effector mechanisms, including GATA4 and ANP.
      This effect of sorafenib may be of clinical importance in modulating the
      maladaptive hypertrophic response to pressure overload.

PMID- 24885950
TI  - Ex vivo anti-malarial drugs sensitivity profile of Plasmodium falciparum field
      isolates from Burkina Faso five years after the national policy change.
AB  - BACKGROUND: The recent reports on the decreasing susceptibility of Plasmodium
      falciparum to artemisinin derivatives along the Thailand and Myanmar border are
      worrying. Indeed it may spread to India and then Africa, repeating the same
      pattern observed for chloroquine resistance. Therefore, it is essential to start
      monitoring P. falciparum sensitivity to artemisinin derivatives and its partner
      drugs in Africa. Efficacy of AL and ASAQ were tested by carrying out an in vivo
      drug efficacy test, with an ex vivo study against six anti-malarial drugs nested
      into it. Results of the latter are reported here. METHODS: Plasmodium falciparum
      ex-vivo susceptibility to chloroquine (CQ), quinine (Q), lumefantrine (Lum),
      monodesethylamodiaquine (MDA), piperaquine (PPQ) and dihydroartemisinin (DHA) was
      investigated in children (6 months - 15 years) with a parasitaemia of at least
      >=4,000/MUl. The modified isotopic microtest technique was used. The results of
      cellular proliferation were analysed using ICEstimator software to determine the
      50% inhibitory concentration (IC50) values. RESULTS: DHA was the most potent
      among the 6 drugs tested, with IC50 values ranging from 0.8 nM to 0.9 nM
      (Geometric mean IC50 = 0.8 nM; 95% CI [0.8 - 0.9]). High IC50 values ranged
      between 0.8 nM to 166.1 nM were reported for lumefantrine (Geometric mean IC50 =
      25.1 nM; 95% CI [22.4 - 28.2]). MDA and Q IC50s were significantly higher in CQ
      resistant than in CQ-sensitive isolates (P = 0.0001). However, the opposite
      occurred for Lum and DHA (P < 0.001). No difference was observed for PPQ.
      CONCLUSION: Artemisinin derivatives are still very efficacious in Burkina Faso
      and DHA-PPQ seems a valuable alternative ACT. The high lumefantrine IC50 found in
      this study is worrying as it may indicate a decreasing efficacy of one of the
      first-line treatments. This should be further investigated and monitored over
      time with large in vivo and ex vivo studies that will include also plasma drug
      measurements.

PMID- 24885952
TI  - Probable novel PSEN2 Val214Leu mutation in Alzheimer's disease supported by
      structural prediction.
AB  - BACKGROUND: PSEN2 mutations are rare variants, and fewer than 30 different PSEN2
      mutations have been found. So far, it has not been reported in Asia. CASE
      PRESENTATION: PSEN2 mutation at codon 214 for predicting a valine to leucine
      substitution was found in a 70-year-old woman, who showed a dementia of the
      Alzheimer type. We did not find the mutation in 614 control chromosomes. We also
      predicted the structures of presenilin 2 protein with native Val 214 residue and
      Leu 214 mutation, which revealed significant structural changes in the region.
      CONCLUSION: It could be a novel mutation verified with structural prediction in a
      patient with Alzheimer's disease.

PMID- 24885953
TI  - Quality and safety issues highlighted by patients in the handling of laboratory
      test results by general practices--a qualitative study.
AB  - BACKGROUND: In general practice internationally, many care teams handle large
      numbers of laboratory test results relating to patients in their care. Related
      research about safety issues is limited with most of the focus on this workload
      from secondary care and in North American settings. Little has been published in
      relation to primary health care in the UK and wider Europe. This study aimed to
      explore experiences and perceptions of patients with regards to the handling of
      test results by general practices. METHODS: A qualitative research approach was
      used with patients. The setting was west of Scotland general practices from one
      National Health Service territorial board area. Patients were purposively sampled
      from practice held lists of patients who received a number of laboratory tests
      because of chronic medical problems or surveillance of high risk medicines. Focus
      groups were held and were audio-recorded. Tapes were transcribed and subjected to
      qualitative analysis. Transcripts were coded and codes merged into themes by two
      of the researchers. RESULTS: 19 participants from four medical practices took
      part in four focus groups. The main themes identified were: 1. Patients lacked
      awareness of the results handling process in their practice. 2. Patients usually
      did not contact their practice for test results, unless they considered
      themselves to be ill. 3. Patients were concerned about the appropriateness of
      administrators being involved in results handling. 4. Patients were concerned
      about breaches of confidentiality when administrators were involved in results
      handling. 5. Patients valued the use of dedicated results handling staff. 6.
      Patients welcomed the use of technology to alert them to results being available,
      and valued the ability to choose how this happened. CONCLUSIONS: The study
      confirms the quality and safety of care problems associated with results handling
      systems and adds to our knowledge of the issues that impact in these areas.
      Practices need to be aware that patients may not contact them about results, and
      they need to publicise their results handling processes to patients and take
      steps to reassure patients about confidentiality with regards to administrators.

PMID- 24885954
TI  - Surface aggregation patterns of LDL receptors near coated pits III: potential
      effects of combined retrograde membrane flow-diffusion and a polarized-insertion
      mechanism.
AB  - Although the process of endocytosis of the low density lipoprotein (LDL)
      macromolecule and its receptor have been the subject of intense experimental
      research and modeling, there are still conflicting hypotheses and even
      conflicting data regarding the way receptors are transported to coated pits, the
      manner by which receptors are inserted before they aggregate in coated pits, and
      the display of receptors on the cell surface. At first it was considered that LDL
      receptors in human fibroblasts are inserted at random locations and then
      transported by diffusion toward coated pits. But experiments have not ruled out
      the possibility that the true rate of accumulation of LDL receptors in coated
      pits might be faster than predicted on the basis of pure diffusion and uniform
      reinsertion over the entire cell surface. It has been claimed that recycled LDL
      receptors are inserted preferentially in regions where coated pits form, with
      display occurring predominantly as groups of loosely associated units. Another
      mechanism that has been proposed by experimental cell biologists which might
      affect the accumulation of receptors in coated pits is a retrograde membrane
      flow. This is essentially linked to a polarized receptor insertion mode and also
      to the capping phenomenon, characterized by the formation of large patches of
      proteins that passively flow away from the regions of membrane exocytosis. In
      this contribution we calculate the mean travel time of LDL receptors to coated
      pits as determined by the ratio of flow strength to diffusion-coefficient, as
      well as by polarized-receptor insertion. We also project the resulting display of
      unbound receptors on the cell membrane. We found forms of polarized insertion
      that could potentially reduce the mean capture time of LDL receptors by coated
      pits which is controlled by diffusion and uniform insertion. Our results show
      that, in spite of its efficiency as a possible device for enhancement of the rate
      of receptor trapping, polarized insertion nevertheless fails to induce the
      formation of steady-state clusters of receptor on the cell membrane. Moreover,
      for appropriate values of the flow strength-diffusion ratio, the predicted steady
      state distribution of receptors on the surface was found to be consistent with
      the phenomenon of capping. 

PMID- 24885955
TI  - Survival advantage of partial over radical nephrectomy in patients presenting
      with localized renal cell carcinoma.
AB  - BACKGROUND: Partial nephrectomy (PN) preserves renal function and has become the
      standard approach for T1a renal cell carcinoma (RCC). However, there is still an
      ongoing debate as to which patients will actually derive greater benefit from
      partial than from radical nephrectomy (RN). The aim of this study was to
      retrospectively evaluate the impact of the type of surgery on overall survival
      (OS) in patients with localized RCC. METHODS: Renal surgery was performed in 4326
      patients with localized RCC (pT <= 3a N/M0) at six German tertiary care centers
      from 1980 to 2010: RN in 2955 cases (68.3%), elective (ePN) in 1108 (25.6%), and
      imperative partial nephrectomy (iPN) in 263 (6.1%) cases. The median follow-up
      for all patients was 63 months. Kaplan-Meier and Cox regression analyses were
      carried out to identify prognosticators for OS. RESULTS: PN was performed
      significantly more often than RN in patients presenting with lower tumor stages,
      higher RCC differentiation, and non-clear cell histology. Accordingly, the
      calculated 5 (10)-year OS rates were 90.0 (74.6)% for ePN, 83.9 (57.5)% for iPN,
      and 81.2 (64.7)% for RN (p < 0.001). However, multivariate analysis including
      age, sex, tumor diameter and differentiation, histological subtype, and the year
      of surgery showed that ePN compared to RN still qualified as an independent
      factor for improved OS (HR 0.79, 95% CI 0.66-0.94, p = 0.008). CONCLUSION: Even
      allowing for the weaknesses of this retrospective analysis, our multicenter study
      indicates that in patients with localized RCC, PN appears to be associated with
      better OS than RN irrespective of age or tumor size.

PMID- 24885956
TI  - Relationship of perceived environmental barriers and disability in community
      dwelling elderly in Taiwan--a population-based study.
AB  - BACKGROUND: To identify the relationship between perceived environmental barriers
      and disability in community-dwelling elderly. METHODS: Cross-sectional study in
      two community service centers in Tainan. We enrolled 200 community-dwelling
      residents, aged above 65 years, who had resided in the same community for at
      least 12 months. Basic activity of daily living (BADL) and instrumental activity
      of daily living (IADL) were assessed using the Hierarchy of Care Required (HCR).
      There were 59 participants in BADL disability and 109 in IADL disability.
      Perceived environmental barriers were assessed using the Craig Hospital Inventory
      of Environmental Factors (CHIEF). We used multinomial logistic regression to
      examine the relationship of perceived environmental barriers and disability.
      RESULTS: The presence of perceived environmental barriers was related to BADL
      disability (OR = 4.39, 95% CI = 1.01-19.11) and IADL disability (IADL with
      difficulty in 1-2 tasks: OR = 9.93, 95% CI = 3.22-30.56; IADL with difficulty in
      more than 2 tasks: OR = 8.40, 95% CI = 1.83-38.51). The presence of
      physically/structurally perceived environmental barriers was related to BADL
      disability (OR = 4.90, 95% CI = 1.01-23.86) and IADL disability (IADL with
      difficulty in 1-2 tasks: OR = 4.61, 95% CI = 1.27-16.76; IADL with difficulty in
      more than 2 tasks: OR = 17.05, 95% CI = 2.82-103.30). CONCLUSIONS: Perceived
      environmental barriers are related to disability in community-dwelling elderly.

PMID- 24885957
TI  - MEIGO: an open-source software suite based on metaheuristics for global
      optimization in systems biology and bioinformatics.
AB  - BACKGROUND: Optimization is the key to solving many problems in computational
      biology. Global optimization methods, which provide a robust methodology, and
      metaheuristics in particular have proven to be the most efficient methods for
      many applications. Despite their utility, there is a limited availability of
      metaheuristic tools. RESULTS: We present MEIGO, an R and Matlab optimization
      toolbox (also available in Python via a wrapper of the R version), that
      implements metaheuristics capable of solving diverse problems arising in systems
      biology and bioinformatics. The toolbox includes the enhanced scatter search
      method (eSS) for continuous nonlinear programming (cNLP) and mixed-integer
      programming (MINLP) problems, and variable neighborhood search (VNS) for Integer
      Programming (IP) problems. Additionally, the R version includes BayesFit for
      parameter estimation by Bayesian inference. The eSS and VNS methods can be run on
      a single-thread or in parallel using a cooperative strategy. The code is supplied
      under GPLv3 and is available at http://www.iim.csic.es/~gingproc/meigo.html.
      Documentation and examples are included. The R package has been submitted to
      BioConductor. We evaluate MEIGO against optimization benchmarks, and illustrate
      its applicability to a series of case studies in bioinformatics and systems
      biology where it outperforms other state-of-the-art methods. CONCLUSIONS: MEIGO
      provides a free, open-source platform for optimization that can be applied to
      multiple domains of systems biology and bioinformatics. It includes efficient
      state of the art metaheuristics, and its open and modular structure allows the
      addition of further methods.

PMID- 24885958
TI  - The effectiveness of job rotation to prevent work-related musculoskeletal
      disorders: protocol of a cluster randomized clinical trial.
AB  - BACKGROUND: Job rotation has often been used in situations where the level of
      exposure cannot be reduced due to the characteristics of the job or through
      physical measures. However, the effectiveness of the job rotation strategy at
      preventing musculoskeletal complaints lacks adequate scientific data.
      METHODS/DESIGN: A cluster randomized controlled trial will be used to investigate
      the effectiveness of job rotation to prevent musculoskeletal disorders in
      industrial workers. The randomized cluster was based in characteristics of
      production sectors. A total cluster will be 4 sectors, and 957 workers will be
      recruited from a textile industry and randomly allocated into intervention or
      control groups. Both groups will receive training on ergonomics guidelines. In
      addition, the intervention group will perform job rotation, switching between
      tasks with low, moderate, and high risk for musculoskeletal complaints. The
      primary outcome will be the number of working hours lost due to sick leave by
      musculoskeletal injuries recorded in employee administrative data bases.
      Secondary outcomes measured via survey include: body parts with musculoskeletal
      pain, the intensity of this pain, physical workload, fatigue, general health
      status, physical activity level, and work productivity. Secondary outcome
      measures will be assessed at baseline and after 3, 6, 9, and 12 months. The cost
      effectiveness analysis will be performed from the societal and company
      perspective. DISCUSSION: Prevention of work-related musculoskeletal disorders is
      beneficial for workers, employers, and society. The results of this study will
      provide new information about the effectiveness of job rotation as a strategy to
      reduce work-related musculoskeletal disorders. TRIAL REGISTRATION: NCT01979731,
      November 3, 2013.

PMID- 24885960
TI  - Why is high-quality research on palliative care so hard to do? Barriers to
      improved research from a survey of palliative care researchers.
AB  - BACKGROUND: Substantial agreement has been achieved on research priorities in
      palliative care over the past 15 years, as evidenced by consensus conferences and
      systematic reviews. Despite the presence of a widely endorsed research agenda,
      however, addressing the gaps in scientific knowledge has progressed slowly,
      suggesting that researchers face significant obstacles to conducting high-quality
      research on the most pressing topics in the field. OBJECTIVE: To systematically
      identify barriers to improved and expanded palliative care research as reported
      by researchers. DESIGN: Semistructured telephone interviews to solicit barriers
      to research in palliative care. SETTING/SUBJECTS: A purposive, interdisciplinary
      sample of 61 leading researchers in palliative care. MEASUREMENTS: Interviews
      were transcribed and analyzed using standard qualitative methods. RESULTS:
      Respondents named five barriers impeding progress: (1) funding, (2) institutional
      capacity, (3) researcher workforce, (4) challenges related to the topic and
      population (e.g., attrition, heightened human subjects protections), and (5)
      public and professional misunderstanding of palliative care and aversion to
      topics related to serious illness and end-of-life. CONCLUSIONS: Research in
      palliative care is being held back by significant barriers that require the
      attention of institutions and funders. The consensus within the interdisciplinary
      sample indicates that concentrated effort to address barriers related to funding
      and researcher workforce could facilitate progress on established research
      priorities. More research is needed on viable strategies for overcoming the
      identified barriers.

PMID- 24885959
TI  - Gene bionetworks involved in the epigenetic transgenerational inheritance of
      altered mate preference: environmental epigenetics and evolutionary biology.
AB  - BACKGROUND: Mate preference behavior is an essential first step in sexual
      selection and is a critical determinant in evolutionary biology. Previously an
      environmental compound (the fungicide vinclozolin) was found to promote the
      epigenetic transgenerational inheritance of an altered sperm epigenome and
      modified mate preference characteristics for three generations after exposure of
      a gestating female. RESULTS: The current study investigated gene networks
      involved in various regions of the brain that correlated with the altered mate
      preference behavior in the male and female. Statistically significant
      correlations of gene clusters and modules were identified to associate with
      specific mate preference behaviors. This novel systems biology approach
      identified gene networks (bionetworks) involved in sex-specific mate preference
      behavior. Observations demonstrate the ability of environmental factors to
      promote the epigenetic transgenerational inheritance of this altered evolutionary
      biology determinant. CONCLUSIONS: Combined observations elucidate the potential
      molecular control of mate preference behavior and suggests environmental
      epigenetics can have a role in evolutionary biology.

PMID- 24885961
TI  - 10-year-old girl with life-threatening idiopathic systemic capillary leak
      syndrome: a case report.
AB  - BACKGROUND: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare
      disorder, characterized by episodic life-threatening hypotension,
      hypoalbuminemia, and hemoconcentration. CASE PRESENTATION: A 10-year-old girl
      presented with abdominal pain, vomiting, diarrhea, fever and developed
      generalized edema a day after admission. Clinical and laboratory findings were
      consistent with ISCLS. She received aggressive fluid replacement,
      methylprednisolone pulse (30 mg/kg/day), high-dose intravenous immunoglobulin
      (IVIG, 2 g/kg/day) and plasma exchange in acute phase. She received fasciotomy of
      bilateral lower extremities as she developed complications of compartment
      syndrome. Since there were two episodes of ISCLS attacks, theophylline and
      terbutaline were initiated for prevention of attacks and then the remission is
      currently maintained. Because of high fatality rate in ISCLS, prompt diagnosis
      and intervention are very important. CONCLUSION: We describe here, a rare case of
      pediatric ISCLS. ISCLS should be considered as a differential diagnosis, when the
      patient presents with unexplained or sudden hypovolemic shock. Reports on
      pediatrics ISCLS are very few, and accumulation of similar case reports is
      needed.

PMID- 24885962
TI  - Effect of genetic deletion and pharmacological antagonism of P2X7 receptors in a
      mouse animal model of migraine.
AB  - BACKGROUND: Purine receptors participate in peripheral and central sensitization
      and are associated with migraine headache. We investigated the role of P2X7
      receptor (P2X7) in a nitroglycerin (NTG)-induced mouse model of migraine.
      METHODS: Intraperitoneal NTG injection (15 mg/kg) triggered thermal hyperalgesia
      in the hindpaws of wild-type C57BL/6J mice, followed by the induction of c-fos in
      upper cervical spinal cord and trigeminal nucleus caudalis. The effect of genetic
      deletion of P2X7 and the selective P2X7 antagonist Brilliant Blue G (BBG) were
      examined on hyperalgesia and c-fos induction. RESULTS: NTG decreased the paw
      withdrawal threshold in both wild-type and P2X7 knockout mice. Nevertheless,
      subacute BBG treatment (50 mg/kg/day i.p.) completely prevented the effect of NTG
      in wild-type, but not in knockout mice. Whereas P2X7 deficiency differentially
      affected the expression of c-fos, the average number of fos-immuno-reactive
      neurons in trigeminal nucleus caudalis, but not in upper cervical spinal cord was
      lower in BBG-treated wild-type mice after NTG treatment. CONCLUSIONS: Our results
      show that P2X7 receptors might participate in the pathogenesis of migraine,
      although upregulation of other P2X receptors probably compensate for the loss of
      its action in knockout mice. The data also suggest the therapeutic potential of
      P2X7 antagonists for the treatment of migraine.

PMID- 24885963
TI  - Association between hepatitis B virus infection and metabolic syndrome: a
      retrospective cohort study in Shanghai, China.
AB  - BACKGROUND: Metabolic syndrome (MS) and hepatitis B (HBV) infection are two major
      public health problems in China. There are few studies about their association,
      and the results of these studies are contradictory. We conducted a retrospective
      cohort study to assess the association between MS and HBV in a Shanghai community
      based cohort. METHODS: Nine hundred seventy-six Shanghai residents were recruited
      from the Putuo community. 480 HBV infections were in exposed group and 496 non
      infections in unexposed group. All metabolic-related parameters and hepatitis B
      serology were tested with routine biochemical or immunological methods. "Exposed"
      was defined by HBV infection represented by hepatitis B surface antigen (HBsAg)
      and without anti-virus treatment. "Unexposed" were subjects who didn't infect
      with HBV (Represented by HBsAg) and no MS when they entered the cohort. MS was
      defined based on the updated National Cholesterol Education Program Adult
      Treatment Panel III criteria. The Cox proportional hazards model was used to
      estimate the hazard ratios (HR) and related 95% confidence intervals (95% CI) for
      the association between HBV infection and MS over a 20-year follow-up period.
      RESULTS: Of 976 subjects recruited, 480 had latent HBV infection (exposed
      subjects). After adjusting for age, the crude HR was 2.46 (95% CI: 1.77, 3.41).
      After adjusting for potential risk factors of MS (age, gender, smoking, passive
      smoking, alcohol consumption, physical activity, and diet), the HR was 2.27 (95%
      CI: 1.52, 3.38). CONCLUSIONS: This 20-year follow-up retrospective cohort study
      in Shanghai showed a positive association between HBV infection and MS.

PMID- 24885964
TI  - Modulation of insulin/IGFs pathways by sirtuin-7 inhibition in drug-induced
      chemoreistance.
AB  - BACKGROUND: Insulin and insulin-like growth factors (IGFs) are key regulators of
      metabolism and growth. Recent evidences suggest a key role of these pathways in
      non-classical tissues and the metabolic pathways by which these hormones exert
      their effects in neoplasia is unclear. AIMS: To study insulin/IGFs pathways in
      drug sensitive and resistant cancer cells representing breast cancer (MCF-7),
      osteosarcoma (SaOS-2), and ovarian cancer (A2780) and to examine the effect of
      Sirtuin-7 (Sirt7) inhibition on insulin/IGFs pathways in MCF-7 cell line.
      METHODS: Drug resistant cells were generated by continuous incubation of parental
      cell lines with stepwise increases in Doxorubicin or Cisplatin over a period of 3
      to 6 months. MCF-7 cells were transfected with cloned hairpin siRNA template for
      Sirt7 using the Amaxa GmbH transfection system. mRNA expression of Sirt7, INSR,
      IRS-1, IRS-2, IRS-4, IGF-1, IGF-2, MDR-1, MRP-1, BCRP was measured by qPCR and
      Sirt7 by standard Western blotting. FITC-insulin uptake was imaged with Leica
      Confocal Microscope. RESULTS: Insulin receptor (INSR), insulin receptor substrate
      1 (IRS-1) were inhibited in drug-induced resistance, whereas IRS-2 was
      significantly induced in all the chemoresistant cells tested when compared to
      their parental counterparts. IGF-1 and IGF-2 were also upregulated in all the
      drug resistant cells tested. Sirt7 was significantly reduced in all
      chemoresistant cells tested. Knockdown of Sirt7 expression in human breast MCF-7
      cell line by siRNA induced premature senescence-like phenotype and multi-drug
      resistance, suggesting that this gene may play an active role in regulating
      cancer cell response to stress. Suppression of Sirt7 selectively inhibited INSR
      and IRS-1, whereas it had minimal effect on that of IRS-2. Sirt7 suppression in
      MCF-7 also inhibited insulin uptake. Additionally, Sirt7 inhibition upregulated
      IGF-1, IGF-2 and IGFR expression. CONCLUSION: Our data demonstrate that stress
      induced Sirt7 inhibition significantly increases stress resistance and modulates
      insulin/IGF-1 signaling pathways. More importantly, this study links Sir2 family
      proteins to insulin/IGF signaling in drug-induced stress resistance in neoplasia.
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1135426681234493.

PMID- 24885965
TI  - A rare case of Cytomegalovirus, Scedosporium apiospermum and Mycobacterium
      tuberculosis in a renal transplant recipient.
AB  - BACKGROUND: Renal transplant recipients are at high risk of developing multiple
      infections, often concomitantly because of their immunocompromised status. Post
      renal transplant infections are often elusive and require extensive evaluation
      for proper diagnosis and treatment. A high index of suspicion is required and an
      attempt should be made to confirm the microbiological diagnosis from each site
      involved to rule out multiple infections. CASE PRESENTATION: We report a 50-year
      old female, a renal allograft recipient who presented with left hemiplegia,
      esophageal ulcers and fever 3 months after her transplant. Esophageal biopsy
      revealed Cytomegalovirus (CMV) inclusions and the whole blood quantitative CMV
      polymerase chain reaction (PCR) was positive. Neuroimaging showed a brain
      abscess, stereotactic biopsy from which revealed Scedosporium apiospermum on
      fungal culture. Her tacrolimus and mycophenolate were stopped and she was managed
      with intravenous ganciclovir and voriconazole. With these measures, she showed
      marked improvement in her general and neurological condition. Two months later,
      she developed recurrence of fever with dry cough. Radiological investigation
      revealed a cavitating lung lesion, a needle aspiration from which demonstrated
      acid-fast bacilli. She was started on antituberculous treatment. With these
      measures, she recovered completely and maintained good graft function despite
      being on only prednisolone 10 mg once a day. CONCLUSION: Although CMV disease is
      not uncommon in the first three months post transplant, Scedosporium is a rare
      cause of brain abscess. On the other hand, tuberculosis is common in transplant
      recipients, especially in developing countries, like India. However, this is the
      first case report of occurrence of these three infections in the same patient,
      demonstrating the importance of a good microbiological work-up from each site
      involved in immunosuppressed subjects.

PMID- 24885966
TI  - Olanzapine is superior to lamotrigine in the prevention of bipolar depression: a
      naturalistic observational study.
AB  - BACKGROUND: Bipolar disorder is a highly recurrent disease and has great impact
      on the function of patients. Depressive symptoms consist of more than 50% of life
      time during the illness and may lead to self harm or suicidal behaviors. Little
      is known about the antidepressant effects of olanzapine, an atypical
      antipsychotic, as monotherapy despite its indication for preventing manic
      episodes. In contrast, lamotrigine, a mood stabilizer, has been proven to be
      effective in preventing depression in patients with bipolar disorder. However, no
      studies have compared the efficacy between lamotrigine and olanzapine in the
      maintenance treatment of bipolar disorder. This enriched naturalistic study was
      implemented to assess the effectiveness of olanzapine and lamotrigine as
      monotherapy in the prevention of recurrence of bipolar disorder. METHODS:
      Patients with bipolar disorder in a euthymic state (Young's Mania Rating Scale
      (YMRS) score <12, and 21-item Hamilton Depression Rating Scale (HAM-D) score <7)
      for at least two months, having already received either olanzapine or lamotrigine
      as the maintenance treatment were recruited. The patients maintained with
      olanzapine (n = 22) were applied to olanzapine group whereas those maintained
      with lamotrigine (n = 29) were applied to lamotrigine group. They were followed
      up for 12 months. Differences in the efficacy between olanzapine and lamotrigine
      in recurrence prevention were analyzed. The Kaplan-Meier method was used to
      generate time-to-recurrence curves, and differences between the two groups were
      compared using the log-rank test. RESULTS: Olanzapine had a significantly lower
      recurrence rate of depressive episodes than lamotrigine (20.0% vs. 57.7%, chi2 =
      6.62, p = .010). However, olanzapine and lamotrigine had similar mania (15.0% vs.
      0%, chi2 = 4.17, p = .075, Fisher's exact test) and any mood episode (35.0% vs.
      57.7%, chi2 = 2.33, p = .127) recurrence rates. Olanzapine was significantly
      superior to lamotrigine in the time to recurrence of depressive episodes (chi2 =
      4.55, df = 1, p = .033), but there was no difference in the time to recurrence of
      any mood episode (chi2 = 1.68, df = 1, p = .195). CONCLUSIONS: This prospective
      naturalistic study suggests that olanzapine is more effective than lamotrigine in
      the prevention of depressive episodes in patients with bipolar disorder. Future
      large-scale randomized studies are warranted to validate our results. TRIAL
      REGISTRATION: ClinicalTrials.gov ID NCT01864551.

PMID- 24885967
TI  - Prognostic significance of the number of tumors and aggressive surgical approach
      in colorectal cancer hepatic metastasis.
AB  - BACKGROUND: Although liver resection (LR) for colorectal cancer (CRC) hepatic
      metastasis is the best strategy to improve patient outcomes, there are
      considerable concerns regarding the recurrence of CRC after LR. In this study, we
      investigated the prognostic indicators associated with CRC recurrence after LR
      for hepatic metastasis. METHODS: This is a retrospective review of patients who
      underwent curative LR for CRC hepatic metastasis between January 2008 and
      December 2012. The clinicopathological features and outcome parameters affecting
      prognosis were analyzed. RESULTS: A total of 332 LRs with curative intent were
      performed in 278 patients, of whom 168 (60.4%) experienced CRC recurrence after
      the first LR, and 206 of the 332 LRs (62.0%) developed CRC recurrence. A
      preoperative serum carcinoembryonic antigen level greater than 100 ng/mL and four
      or more metastatic tumor nodules were independent prognostic factors for CRC
      recurrence after LR. The disease-free survival rate after LR was significantly
      associated with the number of metastatic nodules. The patients who underwent
      surgical resection for recurrent CRC had favorable outcomes, with a five-year
      overall survival rate of 65.2%. CONCLUSION: The number of metastatic tumors
      significantly affects the outcomes of patients who undergo LR for CRC hepatic
      metastasis, indicating that a novel therapeutic strategy for patients at high
      risk may be required. However, favorable long-term outcomes are achievable
      through aggressive treatment with surgical resection of the recurrent CRC.

PMID- 24885968
TI  - Aspergillus oryzae-based cell factory for direct kojic acid production from
      cellulose.
AB  - BACKGROUND: Kojic acid (5-Hydroxy-2-(hydroxymethyl)-4-pyrone) is one of the major
      secondary metabolites in Aspergillus oryzae. It is widely used in food,
      pharmaceuticals, and cosmetics. The production cost, however, is too high for its
      use in many applications. Thus, an efficient and cost-effective kojic acid
      production process would be valuable. However, little is known about the complete
      set of genes for kojic acid production. Currently, kojic acid is produced from
      glucose. The efficient production of kojic acid using cellulose as an inexpensive
      substrate would help establish cost-effective kojic acid production. RESULTS: A
      kojic acid transcription factor gene over-expressing the A. oryzae strain was
      constructed. Three genes related to kojic acid production in this strain were
      transcribed in higher amounts than those found in the wild-type strain. This
      strain produced 26.4 g/L kojic acid from 80 g/L glucose. Furthermore, this strain
      was transformed with plasmid harboring 3 cellulase genes. The resultant A. oryzae
      strain successfully produced 0.18 g/L of kojic acid in 6 days of fermentation
      from the phosphoric acid swollen cellulose. CONCLUSIONS: Kojic acid was produced
      directly from cellulose material using genetically engineered A. oryzae. Because
      A. oryzae has efficient protein secretion ability and secondary metabolite
      productivity, an A. oryzae-based cell factory could be a platform for the
      production of various kinds of bio-based chemicals.

PMID- 24885969
TI  - Humoral responses in Rhodnius prolixus: bacterial feeding induces differential
      patterns of antibacterial activity and enhances mRNA levels of antimicrobial
      peptides in the midgut.
AB  - BACKGROUND: The triatomine, Rhodnius prolixus, is a major vector of Trypanosoma
      cruzi, the causative agent of Chagas disease in Latin America. It has a strictly
      blood-sucking habit in all life stages, ingesting large amounts of blood from
      vertebrate hosts from which it can acquire pathogenic microorganisms. In this
      context, the production of antimicrobial peptides (AMPs) in the midgut of the
      insect is vital to control possible infection, and to maintain the microbiota
      already present in the digestive tract. METHODS: In the present work, we studied
      the antimicrobial activity of the Rhodnius prolixus midgut in vitro against the
      Gram-negative and Gram-positive bacteria Escherichia coli and Staphylococcus
      aureus, respectively. We also analysed the abundance of mRNAs encoding for
      defensins, prolixicin and lysozymes in the midgut of insects orally infected by
      these bacteria at 1 and 7 days after feeding. RESULTS: Our results showed that
      the anterior midgut contents contain a higher inducible antibacterial activity
      than those of the posterior midgut. We observed that the main AMP encoding mRNAs
      in the anterior midgut, 7 days after a blood meal, were for lysozyme A, B,
      defensin C and prolixicin while in the posterior midgut lysozyme B and prolixicin
      transcripts predominated. CONCLUSION: Our findings suggest that R. prolixus
      modulates AMP gene expression upon ingestion of bacteria with patterns that are
      distinct and dependent upon the species of bacteria responsible for infection.

PMID- 24885970
TI  - HIV vaccine acceptability among high-risk drug users in Appalachia: a cross
      sectional study.
AB  - BACKGROUND: A vaccine could substantially impact the HIV epidemic, but inadequate
      uptake is a serious concern. Unfortunately, people who use drugs, particularly
      those residing in rural communities, have been underrepresented in previous
      research on HIV vaccine acceptability. This study examined HIV vaccine
      acceptability among high-risk drug users in a rural community in the United
      States. METHODS: Interviewer-administered questionnaires included questions about
      risk behavior and attitudes toward HIV vaccination from 433 HIV-negative drug
      users (76% with history of injection) enrolled in a cohort study in Central
      Appalachia. HIV vaccine acceptability was measured on a 4-point Likert scale.
      Generalized linear mixed models were used to determine correlates to self-report
      of being "very likely" to receive a 90% effective HIV vaccine (i.e. "maximum
      vaccine acceptability", or MVA). Adjusted odds ratios (AORs) and corresponding
      95% confidence intervals (CIs) are reported. RESULTS: Most (91%) reported that
      they would accept a preventive HIV vaccine, but concerns about cost, dosing,
      transportation constraints, vaccine-induced seropositivity, and confidentiality
      were expressed. Cash incentives, oral-administration, and peer/partner
      encouragement were anticipated facilitators of uptake. In multivariate analysis,
      men were significantly less likely to report MVA (AOR: 0.33, CI: 0.21 - 0.52).
      MVA was more common among participants who believed that they were susceptible to
      HIV (AOR: 2.31, CI: 1.28 - 4.07), that an HIV vaccine would benefit them (AOR:
      2.80, CI: 1.70 - 4.64), and who had positive experiential attitudes toward HIV
      vaccination (AOR: 1.85, CI: 1.08 - 3.17). MVA was also more common among
      participants who believed that others would encourage them to get vaccinated and
      anticipated that their behavior would be influenced by others' encouragement
      (AOR: 1.81, 95% 1.09 - 3.01). CONCLUSIONS: To our knowledge, this study was among
      the first to explore and provide evidence for feasibility of HIV vaccination in a
      rural, high-risk population in the United States. This study provides preliminary
      evidence that gender-specific targeting in vaccine promotion may be necessary to
      promoting vaccine uptake in this setting, particularly among men. The data also
      underscore the importance of addressing perceived risks and benefits, social
      norms, and logistical constraints in efforts to achieve widespread vaccine
      coverage in this high-risk population.

PMID- 24885971
TI  - Patterns of collaboration in complex networks: the example of a translational
      research network.
AB  - BACKGROUND: This paper examines collaboration in a complex translational cancer
      research network (TRN) made up of a range of hospital-based clinicians and
      university-based researchers. We examine the phenomenon of close-knit and often
      introspective clusters of people (silos) and test the extent that factors
      associated with this clustering (geography, profession and past experience)
      influence patterns of current and future collaboration on TRN projects.
      Understanding more of these patterns, especially the gaps or barriers between
      members, will help network leaders to manage subgroups and promote connectivity
      crucial to efficient network function. METHODS: An on-line, whole network survey
      was used to collect attribute and relationship data from all members of the new
      TRN based in New South Wales, Australia in early 2012. The 68 members were drawn
      from six separate hospital and university campuses. Social network analysis with
      UCInet tested the effects of geographic proximity, profession, past research
      experience, strength of ties and previous collaborations on past, present and
      future intended partnering. RESULTS: Geographic proximity and past working
      relationships both had significant effects on the choice of current collaboration
      partners. Future intended collaborations included a significant number of weak
      ties and ties based on other members' reputations implying that the TRN has
      provided new opportunities for partnership. Professional grouping, a significant
      barrier discussed in the translational research literature, influenced past
      collaborations but not current or future collaborations, possibly through the
      mediation of network brokers. CONCLUSIONS: Since geographic proximity is
      important in the choice of collaborators a dispersed network such as this could
      consider enhancing cross site interactions by improving virtual communication
      technology and use, increasing social interactions apart from project related
      work, and maximising opportunities to meet members from other sites. Key network
      players have an important brokerage role facilitating linkages between groups.

PMID- 24885972
TI  - Importance of active case detection in a malaria elimination programme.
AB  - BACKGROUND: With the aim of eliminating malaria from Sri Lanka by 2014, the Anti
      Malaria Campaign of Sri Lanka (AMC) sought the support of Tropical and
      Environmental Disease and Health Associates Private Limited (TEDHA), a private
      sector organization. In 2009, TEDHA was assigned 43 government hospitals in the
      district of Mannar in the Northern Province and in districts of Trincomalee,
      Batticaloa and Ampara in the Eastern Province to carry out malaria surveillance
      to complement the surveillance activities of the AMC. Passive case detection
      (PCD), activated passive case detection (APCD) and active case detection (ACD)
      for malaria have been routinely carried out in Sri Lanka. METHODS: The active
      case detection programme of TEDHA involves screening of populations irrespective
      of the presence of fever or any other signs or symptoms of malaria to detect
      infections and residual parasite carriers. ACD is done by TEDHA in a) high risk
      populations through mobile malaria clinics including armed forces personnel and
      b) pregnant females who visit antenatal clinics for asymptomatic malaria
      infections during the first trimester of pregnancy. Populations are selected in
      consultation with the Regional Malaria Officer of the AMC thus avoiding any
      overlap with the population screened by the government. RESULTS: TEDHA screened
      387,309 individuals in the four districts for malaria by ACD including high risk
      groups and pregnant women between January 2010 and December 2012. During this
      period seven individuals were diagnosed with Plasmodium vivax infections and one
      individual was detected with a mixed infection of P. vivax and Plasmodium
      falciparum. All eight cases were detected by ACD carried out by mobile malaria
      clinics among high risk groups in the Mannar district. CONCLUSION: The progress
      made by Sri Lanka in the malaria elimination drive is largely due to increased
      surveillance and judicious use of control methods which has resulted in zero
      indigenous malaria cases being reported since October 2012. ACD played a major
      role in interrupting malaria transmission in the country.

PMID- 24885973
TI  - Cheating on examinations and its predictors among undergraduate students at
      Hawassa University College of Medicine and Health Science, Hawassa, Ethiopia.
AB  - BACKGROUND: Cheating on examinations in academic institutions is a worldwide
      issue. When cheating occurs in medical schools, it has serious consequences for
      human life, social values, and the economy. This study was conducted to determine
      the prevalence of cheating and identify factors that influence cheating among
      students of Hawassa University College of medicine and health science. METHODS: A
      cross sectional study was conducted from May through June 2013. A pre-tested self
      administered, structured questionnaire was used to collect self-reported data
      regarding cheating. Data were entered and analyzed using SPSS version 20.
      Descriptive statistics were used for data summarization and presentation. Degree
      of association was measured by Chi Square test, with significance level set at p
      = 0.05. Bivariate and multivariate logistic regression analyses were used to
      assess associations. RESULTS: The prevalence of self-reported cheating was found
      to be 19.8% (95% CI = 17.4-21.9). About 12.1% (95% CI = 10.2-13.9) of students
      disclosed cheating on the entrance examination. The majority of students (80.1%
      (95% CI = 77.9-82.3) disclosed that they would not report cheating to
      invigilators even if they had witnessed cheating. Analysis by multiple regression
      models showed that students who cheated in high school were more likely to cheat
      (adjusted OR = 1. 80, 95% CI = 1. 01-3.19) and that cheating was less likely
      among students who didn't cheat on entrance examinations (adjusted OR = 0. 25,
      95% CI = 0. 14-0.45). Dining outside the university cafeteria and receiving
      pocket money of Birr 300 or more were strongly associated with cheating (adjusted
      OR = 3.08, 95% CI = 1.54-6.16 and adjusted OR = 1.69 (95% CI = 1.05-2.72),
      respectively. The odds of cheating among students were significantly higher for
      those who went to private high school, were substance users, and didn't attend
      lectures than for those who attended government schools, were not substance
      abusers, and attended lectures. CONCLUSION: Our findings have important
      implications for development of an institution's policies on academic integrity.
      By extension, they affect the policies of high schools. Increased levels of
      supervision during entrance examination, mandated attendance at lectures, and
      reduction of substance use are likely to reduce cheating. No significant
      association was found with background, level of parental education, grade point
      average, and interest in field of study.

PMID- 24885974
TI  - The more you look, the more you find: challenging results on FDG-PET CT in a
      patient with neurofibromatosis type I.
AB  - BACKGROUND: FDG-PET/CT is part of the standard diagnostic management of a
      patients with a large variety of common and less common malignant tumors, based
      on the increased glucose metabolism within tumors. CASE PRESENTATION: A hybrid
      fluorodeoxyglucose positron emission tomography and computed tomography (FDG
      PET/CT) was performed in a neurofibromatosis patient to rule out relapse of
      malignant peripheral nerve sheet tumor. The scan revealed non-malignant
      neurofibromas, a testis seminoma and hypermetabolic syphilitic granulomata.
      CONCLUSION: This case stresses the need to rule out infectious diseases when
      atypical hypermetabolic lesions are present.

PMID- 24885975
TI  - Synaptosomal-associated protein 25 (Snap-25) gene polymorphism frequency in
      fibromyalgia syndrome and relationship with clinical symptoms.
AB  - BACKGROUND: SNAP-25 protein is contributory to plasma membrane and synaptic
      vesicle fusions that are critical points in neurotransmission. SNAP-25 gene is
      associated with behavioral symptoms, personality and psychological disorders. In
      addition, SNAP-25 protein can be related to different neurotransmitter functions
      due to its association with vesicle membrane transition and fusion. This is
      important because neurologic, cognitive, and psychologic disorders in
      fibromyalgia syndrome (FMS) can be related to this function. This relationship
      may be enlightening for etiopathogenesis of FMS and treatment approaches. We
      aimed to study a SNAP-25 gene polymorphism, which is related to many psychiatric
      diseases, and FMS association in this prospective study. METHODS: We included 71
      patients who were diagnosed according to new criteria and 57 matched healthy
      women in this study. Both groups were evaluated regarding age, height, weight,
      BMI, education level, marital and occupational status. A new diagnosis of FMS was
      made from criteria scoring, SF-36, Beck depression scale, and VAS that were
      applied to the patient group. SNAP-25 gene polymorphism and disease activity
      score correlations were compared. RESULTS: Mean age was 38+/-5,196 and 38.12+/
      4.939 in patient and control groups, respectively (p=0.542). No significant
      difference was found between groups regarding age, height, weight, BMI, education
      level, marital or occupational status (p > 0.05). Ddel T/C genotype was
      significantly higher in the patient group (p = 0.009). MnlI gene polymorphism did
      not show a correlation with any score whereas a significant correlation was found
      between Ddel T/C genotype and Beck depression scale and VAS score (p < 0.05).
      CONCLUSION: FMS etiopathogenesis is not clearly known. Numerous neurologic,
      cognitive and psychological disorders were found during studies looking at cause.
      Our study showed increased SNAP-25 Ddel T/C genotype in FMS patients compared to
      the control group, which is related to behavioral symptoms, personality and
      psychological disorders in FMS patients.

PMID- 24885977
TI  - Haplotype analysis of ApoAI gene and sepsis-associated acute lung injury.
AB  - BACKGROUND: Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high
      density lipoprotein (HDL) which exerts innate protective effects in systemic
      inflammation. However, its role in the acute lung injury (ALI) has not been well
      studied. In the present study we investigated the association between
      polymorphisms of ApoA1 gene and ALI in a Chinese population. METHODS: Three
      polymorphisms of the ApoA1 gene (rs11216153, rs2070665, and rs632153) were
      genotyped by TaqMan method in 290 patients with sepsis-associated ALI, 285
      patients sepsis alone and 330 age- and sex-matched healthy controls. RESULTS: We
      found rs11216153 polymorphism of ApoA1 was associated with ALI, the GG genotype
      and G allele was common in the ALI patients (76.9%, 88.1%, respectively) than
      both in the control subjects (55.8%, 75.8%, respectively) and in the sepsis alone
      patients (58.2%, 78.4%, respectively). Haplotype consisting of these three SNPs
      strengthened the association with ALI susceptibility. The frequency of haplotype
      GTG in the ALI samples was significantly higher than that in the healthy control
      group (OR = 2.261, 95% CI: 1.735 ~ 2.946, P <0.001) and the sepsis alone group
      (OR = 1.789, 95% CI: 1.373 ~ 2.331.P < 0.001). Carriers of the haplotype TTG had
      a lower risk for ALI compared with healthy control group (OR = 0.422, 95% CI:
      0.310 ~ 0.574, P < 0.001) and sepsis alone group (OR = 0.491, 95% CI: 0.356 ~
      0.676, P <0.001). CONCLUSIONS: These results indicated that genetic variants in
      the ApoA1 gene might be associated with susceptibility to sepsis-associated ALI
      in Han Chinese population.

PMID- 24885976
TI  - Systems analysis and improvement to optimize pMTCT (SAIA): a cluster randomized
      trial.
AB  - BACKGROUND: Despite significant increases in global health investment and the
      availability of low-cost, efficacious interventions to prevent mother-to-child
      HIV transmission (pMTCT) in low- and middle-income countries with high HIV
      burden, the translation of scientific advances into effective delivery strategies
      has been slow, uneven and incomplete. As a result, pediatric HIV infection
      remains largely uncontrolled. A five-step, facility-level systems analysis and
      improvement intervention (SAIA) was designed to maximize effectiveness of pMTCT
      service provision by improving understanding of inefficiencies (step one: cascade
      analysis), guiding identification and prioritization of low-cost workflow
      modifications (step two: value stream mapping), and iteratively testing and
      redesigning these modifications (steps three through five). This protocol
      describes the SAIA intervention and methods to evaluate the intervention's impact
      on reducing drop-offs along the pMTCT cascade. METHODS: This study employs a two
      arm, longitudinal cluster randomized trial design. The unit of randomization is
      the health facility. A total of 90 facilities were identified in Cote d'Ivoire,
      Kenya and Mozambique (30 per country). A subset was randomly selected and
      assigned to intervention and comparison arms, stratified by country and service
      volume, resulting in 18 intervention and 18 comparison facilities across all
      three countries, with six intervention and six comparison facilities per country.
      The SAIA intervention will be implemented for six months in the 18 intervention
      facilities. Primary trial outcomes are designed to assess improvements in the
      pMTCT service cascade, and include the percentage of pregnant women being tested
      for HIV at the first antenatal care visit, the percentage of HIV-infected
      pregnant women receiving adequate prophylaxis or combination antiretroviral
      therapy in pregnancy, and the percentage of newborns exposed to HIV in pregnancy
      receiving an HIV diagnosis eight weeks postpartum. The Consolidated Framework for
      Implementation Research (CFIR) will guide collection and analysis of qualitative
      data on implementation process. DISCUSSION: This study is a pragmatic trial that
      has the potential benefit of improving maternal and infant outcomes by reducing
      drop-offs along the pMTCT cascade. The SAIA intervention is designed to provide
      simple tools to guide decision-making for pMTCT program staff at the facility
      level, and to identify low cost, contextually appropriate pMTCT improvement
      strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02023658.

PMID- 24885978
TI  - Socio-ecological predictors of participation and dropout in organised sports
      during childhood.
AB  - BACKGROUND: The purpose of this study was to explore the socio-ecological
      determinants of participation and dropout in organised sports in a nationally
      representative sample of Australian children. METHODS: Data were drawn from Waves
      3 and 4 of the Longitudinal Study of Australian Children. In total, 4042 children
      aged 8.25 (SD = 0.44) years at baseline were included, with 24-months between
      Waves. Socio-ecological predictors were reported by parents and teachers, while
      cognitive and health measures were assessed by trained professionals. All
      predictors were assessed at age 8, and used to predict participation and dropout
      by age 10. RESULTS: Seven variables at age 8 were shown to positively predict
      participation in organised sports at age 10. These included: sex (boy); fewer
      people in household; higher household income; main language spoken at home
      (English); higher parental education; child taken to a sporting event; and,
      access to a specialist PE teacher during primary school. Four variables predicted
      dropout from organised sports by age 10: lower household income; main language
      spoken at home (non-English); lower parental education; and, child not taken to a
      sporting event. CONCLUSIONS: The interplay between child sex, socioeconomic
      indicators, and parental support is important in predicting children's
      participation in organised sports. Multilevel and multicomponent interventions to
      promote participation and prevent dropout should be underpinned by the Socio
      Ecological Model and targeted to high risk populations using multiple levels of
      risk.

PMID- 24885979
TI  - Identification of boron-deficiency-responsive microRNAs in Citrus sinensis roots
      by Illumina sequencing.
AB  - BACKGROUND: Boron (B)-deficiency is a widespread problem in many crops, including
      Citrus. MicroRNAs (miRNAs) play important roles in nutrient deficiencies.
      However, little is known on B-deficiency-responsive miRNAs in plants. In this
      study, we first identified miRNAs and their expression pattern in B-deficient
      Citrus sinensis roots by Illumina sequencing in order to identify miRNAs that
      might be involved in the tolerance of plants to B-deficiency. RESULTS: We
      isolated 52 (40 known and 12 novel) up-regulated and 82 (72 known and 10 novel)
      down-regulated miRNAs from B-deficient roots, demonstrating remarkable metabolic
      flexibility of roots, which might contribute to the tolerance of plants to B
      deficiency. A model for the possible roles of miRNAs in the tolerance of roots to
      B-deficiency was proposed. miRNAs might regulate the adaptations of roots to B
      deficiency through following several aspects: (a) inactivating reactive oxygen
      species (ROS) signaling and scavenging through up-regulating miR474 and down
      regulating miR782 and miR843; (b) increasing lateral root number by lowering
      miR5023 expression and maintaining a certain phenotype favorable for B-deficiency
      tolerance by increasing miR394 expression; (c) enhancing cell transport by
      decreasing the transcripts of miR830, miR5266 and miR3465; (d) improving
      osmoprotection (miR474) and regulating other metabolic reactions (miR5023 and
      miR821). Other miRNAs such as miR472 and miR2118 in roots increased in response
      to B-deficiency, thus decreasing the expression of their target genes, which are
      involved in disease resistance, and hence, the disease resistance of roots.
      CONCLUSIONS: Our work demonstrates the possible roles of miRNAs and related
      mechanisms in the response of plant roots to B-deficiency.

PMID- 24885981
TI  - Does induction of labor for constitutionally large-for-gestational-age fetuses
      identified in utero reduce maternal morbidity?
AB  - BACKGROUND: The number of infants with a birth weight > 97th percentile for
      gestational age has increased over the years. Although some studies have examined
      the interest of inducing labor for fetuses with macrosomia suspected in utero,
      only a few have analyzed this suspected macrosomia according to estimated weight
      at each gestational age. Most studies have focused principally on neonatal rather
      than on maternal (and still less on perineal) outcomes. The principal aim of this
      study was to assess whether a policy of induction of labor for women with a
      constitutionally large-for-gestational-age fetus might reduce the occurrence of
      severe perineal tears; the secondary aims of this work were to assess whether
      this policy would reduce either recourse to cesarean delivery during labor or
      neonatal complications. METHODS: This historical cohort study (n = 3077) analyzed
      records from a French perinatal database. Women without diabetes and with a
      cephalic singleton term pregnancy were eligible for the study. We excluded
      medically indicated terminations of pregnancy and in utero fetal deaths. Among
      the pregnancies with fetuses suspected, before birth, of being large-for
      gestational-age, we compared those for whom labor was induced from >= 37 weeks to
      <= 38 weeks+ 6 days (n = 199) to those with expectant obstetrical management (n =
      2878). In this intention-to-treat analysis, results were expressed as crude and
      adjusted relative risks. RESULTS: The mean birth weight was 4012 g +/- 421 g. The
      rate of perineal lesions did not differ between the two groups in either
      primiparas (aRR: 1.06; 95% CI: 0.86-1.31) or multiparas (aRR: 0.94; 95% CI: 0.84
      1.05). Similarly, neither the cesarean rate (aRR: 1.11; 95% CI: 0.82-1.50) nor
      the risks of resuscitation in the delivery room or of death in the delivery room
      or in the immediate postpartum or of neonatal transfer to the NICU (aRR = 0.94;
      95% CI: 0.59-1.50) differed between the two groups. CONCLUSIONS: A policy of
      induction of labor for women with a constitutionally large-for-gestational-age
      fetus among women without diabetes does not reduce maternal morbidity.

PMID- 24885980
TI  - A community-based cluster randomized survey of noncommunicable disease and risk
      factors in a peri-urban shantytown in Lima, Peru.
AB  - BACKGROUND: An estimated 863 million people-a third of the world's urban
      population-live in slums, yet there is little information on the disease burden
      in these settings, particularly regarding chronic preventable diseases. METHODS:
      From March to May 2012, we conducted a cluster randomized survey to estimate the
      prevalence of noncommunicable diseases (NCDs) and associated risk factors in a
      peri-urban shantytown north of Lima, Peru. Field workers administered a
      questionnaire that included items from the WHO World Health Survey and the WHO
      STEPS survey of chronic disease risk factors. We used logistic regression to
      assess the associations of NCDs and related risk factors with age and gender. We
      accounted for sampling weights and the clustered sampling design using
      statistical survey methods. RESULTS: A total of 142 adults were surveyed and had
      a weighted mean age of 36 years (range 18-81). The most prevalent diseases were
      depression (12%) and chronic respiratory disease (8%), while lifetime prevalence
      of cancer, arthritis, myocardial infarction, and diabetes were all less than 5%.
      Fifteen percent of respondents were hypertensive and the majority (67%) was
      unaware of their condition. Being overweight or obese was common for both genders
      (53%), but abdominal obesity was more prevalent in women (54% vs. 10% in men, p <
      0.001). Thirty-five percent of men binge drank and 34% reported current smoking;
      these behaviors were less common among women (4% binge drank, p < 0.001; 8%
      smoked, p = 0.002). Increasing age was associated with an increased risk of
      abdominal obesity (Odds Ratio (OR) = 1.04, 95% CI = 1.01, 1.07, p = 0.02),
      hypertension (OR = 1.06, 95% CI = 1.02, 1.10, p = 0.006), arthritis (OR = 1.07,
      95% CI = 1.03, 1.11, p < 0.001) and cancer (OR = 1.13, 95% CI = 1.07, 1.20, p <
      0.001) in adjusted models. The prevalences of other NCDs and related risk factors
      were similar when stratified by age or gender. CONCLUSIONS: This study underlines
      the important burden of noncommunicable disease in informal settlements in Peru
      and suggests that prevention and treatment interventions could be optimized
      according to age and gender.

PMID- 24885982
TI  - ALK molecular phenotype in non-small cell lung cancer: CT radiogenomic
      characterization.
AB  - PURPOSE: To present a radiogenomic computed tomographic (CT) characterization of
      anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC)
      (ALK+). MATERIALS AND METHODS: In this HIPAA-compliant institutional review board
      approved retrospective study, CT studies, ALK status, and clinical-pathologic
      data in 172 patients with NSCLC from three institutions were analyzed. A screen
      of 24 CT image traits was performed in a training set of 59 patients, followed by
      random forest variable selection incorporating 24 CT traits plus six clinical
      pathologic covariates to identify a radiogenomic predictor of ALK+ status. This
      predictor was then validated in an independent cohort (n = 113). Test-for
      accuracy and subset analyses were performed. A similar analysis was performed to
      identify a biomarker associated with shorter progression-free survival (PFS)
      after therapy with the ALK inhibitor crizotinib. RESULTS: ALK+ status was
      associated with central tumor location, absence of pleural tail, and large
      pleural effusion. An ALK+ radiogenomic CT status biomarker consisting of these
      three imaging traits with patient age of younger than 60 years showed strong
      discriminatory power for ALK+ status, with a sensitivity of 83.3% (15 of 18), a
      specificity of 77.9% (74 of 95), and an accuracy of 78.8% (89 of 113) in
      independent testing. The discriminatory power was particularly strong in patients
      with operable disease (stage IIIA or lower), with a sensitivity of 100.0% (five
      of five), a specificity of 88.1% (37 of 42), and an accuracy of 89.4% (42 of 47).
      Tumors with a disorganized vessel pattern had a shorter PFS with crizotinib
      therapy than tumors without this trait (11.4 vs 20.2 months, P = .041).
      CONCLUSION: ALK+ NSCLC has distinct characteristics at CT imaging that, when
      combined with clinical covariates, discriminate ALK+ from non-ALK tumors and can
      potentially identify patients with a shorter durable response to crizotinib.

PMID- 24885984
TI  - Effects of Bromelia pinguin (Bromeliaceae) on soil ecosystem function and fungal
      diversity in the lowland forests of Costa Rica.
AB  - BACKGROUND: Bromelia pinguin (Bromeliaceae) is a terrestrial bromeliad commonly
      found under forest stands throughout the Neotropics that has been shown to have
      antifungal activity in vitro. We have hypothesized that this bromeliad would also
      have an effect on the fungal populations in nearby soil by decreasing
      fungaldiversity and negatively impacting C and N cycle-related activities. A
      previous study in the lowland forest of Costa Rica showed the soil beneath these
      bromeliads had decreased fungal ITS DNA and differences in C and N levels
      compared to adjacent primary forest soils. RESULTS: In this follow-up study, we
      found that the bromeliad soils had lower rates of C and N biomass development and
      lower phenol oxidase activity (suggesting less decreased fungal decomposition
      activity). The results of T-RFLP and cloning-based taxonomic analyses showed the
      community level diversity and abundance of fungal ITS DNA was less in bromeliad
      soils. Sequence analysis of fungal ITS DNA clones showed marked differences in
      fungal community structure between habitats of Basidiomycota (Tremellales,
      Agricales, Thelephorales), Ascomycota (Helotiales), and Zycomycota populations.
      CONCLUSIONS: The data show there to be differences in the soil nutrient dynamics
      and fungal community structure and activity associated with these bromeliads, as
      compared to the adjacent primary forest. This suggests the possibility that the
      anti-fungal activity of the bromeliad extends into the soil. The bromeliad-dense
      regions of these primary forest habitats provide a unique natural micro-habitat
      within the forests and the opportunity to better identify the role of fungal
      communities in the C and N cycles in tropical soils.

PMID- 24885983
TI  - Porcine circovirus type 2 in China: an update on and insights to its prevalence
      and control.
AB  - Currently, porcine circovirus type 2 (PCV2) is considered the major pathogen of
      porcine circovirus associated-diseases (PCVAD) that causes large economic losses
      for the swine industry in the world annually, including China. Since the first
      report of PCV2 in 1998, it has been drawing tremendous attention for the
      government, farming enterprises, farmers, and veterinary practitioners. Chinese
      researchers have conducted a number of molecular epidemiological work on PCV2 by
      molecular approaches in the past several years, which has resulted in the
      identification of novel PCV2 genotypes and PCV2-like agents as well as the
      description of new prevalence patterns. Since late 2009, commercial PCV2
      vaccines, including the subunit vaccines and inactivated vaccines, have already
      been used in Chinese swine farms. The aim of this review is to update the
      insights into the prevalence and control of PCV2 in China, which would contribute
      to understanding the epidemiology, control measures and design of novel vaccines
      for PCV2. 

PMID- 24885985
TI  - Gender-specific differences in risk for intimate partner violence in South Korea.
AB  - BACKGROUND: Various risk factors of intimate partner violence (IPV) have been
      found to vary by gender. South Korea has one of the highest prevalences of IPV in
      the world; however, little is known about potential risk factors of IPV and
      whether gender influences this relationship. METHODS: Using data from the 2006
      Korea Welfare Panel Study, 8,877 married participants (4,545 men and 4,332 women)
      aged >=30 years were included. Reported IPV was categorized as verbal or physical
      IPV and the association between IPV and related factors was assessed by
      multivariate logistic regression analysis. RESULTS: Women were significantly more
      likely than men were to report IPV victimization (verbal 28.2% vs. 24.4%;
      physical 6.9% vs. 3.4%). Wor odds of physical perpetration than women satisfied
      with their family. Moreover, alcohol intake was significantly associated with IPV
      perpetration and victimization in both genders. CONCLUSION: Significant gender
      specific differences were found among factors related to perpetrating violence
      and being a victim of violence among adults in heterosexual relationships in
      South Korea.

PMID- 24885986
TI  - Anterior chamber bacterial contamination in cataract surgery.
AB  - BACKGROUND: The incidence of postoperative endophthalmitis has reduced during
      last several years to <0.01%; however, its associated complications continue to
      be devastating. Several sources of infection, including contamination by air,
      solutions, surgical instruments, intraocular lens, and wound leakage have been
      identified. The objective of this study was to evaluate the surgical technique,
      antibiotics, and asepsis that are used to reduce the risk of infection during
      cataract surgery. METHODS: This was a transversal prospective study, in which 64
      cataract surgeries were evaluated from 32 patients, with 1 month recovery time;
      and cultures from preoperative and postoperative aspirates were analyzed. Two
      groups were established based on whether preoperative antibiotics were given or
      not. The analysis employed descriptive statistics. RESULTS: Of the 32 patients
      whose aspirates were obtained, three (9.37%) and 10 (31.25%) yielded positive
      cultures preoperative and postoperatively respectively. Staphylococcus species
      was the most common contaminating bacteria. The isolation of Staphylococcus
      species may indicate its potential as exogenous contaminant at time of wound
      closure. The cultures obtained from patients using preoperative antibiotics were
      positive for S. aureus in 10% (n = 2) of cases, and positive in 8.33% (n = 1) of
      cases not using antibiotics. The mean transoperative time with positive growth
      was 67 +/- 17.8 minutes, and with negative growth was 76.3 +/- 25.2 minutes. Two
      surgical techniques were evaluated: phacoemulsification and extracapsular
      extraction. The extracapsular technique showed a contamination rate of 33.33% (n
      = 8) compared to phacoemulsification with a rate of 25% (n = 2) (RR = 1.33).
      CONCLUSIONS: Common contaminating microorganisms included the Staphylococcus
      species, which was isolated from the eyelids and ocular annexes at the time of
      wound closure. The isolation of microorganisms postoperatively could have been
      influenced by the surgical technique used, the surgical time, and the use of
      antibiotics.

PMID- 24885987
TI  - Smear-positive pulmonary tuberculosis and AFB examination practices according to
      the standard checklist of WHO's tuberculosis laboratory assessment tool in three
      governmental hospitals, Eastern Ethiopia.
AB  - BACKGROUND: Using the Directly Observed Treatment-Short course (DOTS) program the
      World Health Organization's global target was to detect 70% of new sputum-smear
      positive PTB cases. Smear positive PTB cases are more infectious than the smear
      negative cases. The TB case detection rate remains very low in Ethiopia, but
      there are increases in smear-negative PTB diagnosis which could be attributed to
      several factors including poor quality of sputum smear-microscopy. METHODS: A
      five years retrospective record review of data between September, 2007 and
      August, 2012 and an in-depth assessment of AFB staining practices of sputum smear
      using a standard checklist were made. The proportion of smear positive cases
      relative to overall Acid Fast Bacilli (AFB) screened was determined over a five
      year period to indicate the overall prevalence and the trend. Odds ratio with 95
      percent confidence interval was calculated for categorical variables using
      multivariate Logistic Regression model to assess the strength of association.
      RESULT: A total of 1266 individuals' data were reviewed. The majority of the
      study participants were male, 704 (55.6%), and rural residents, 690 (54.5%). The
      overall prevalence rate of smear positive PTB was 21.6%. Age categories between
      15-24 and 25-34 years were independent predictors of smear positive PTB with
      adjusted odds ratio of 2.246 [95% CI (1.098-4.597)] and 2.267 [95% CI (1.107
      4.642)], respectively. More males were affected by PTB than females with an
      adjusted odds ratio of 1.426 [95% CI (1.083-1.879)]. An in-depth interview with
      the respective laboratory chiefs showed that quality control measures for sputum
      smear microscopy were used at different levels of the testing activities;
      however, equipment function verification as a quality control measure was not
      accomplished regularly in all of the study hospital laboratories. CONCLUSION: The
      smear positive PTB case detection rate indicated in this study is significantly
      lower than the countries which met the 70% target of the World Health
      Organization. Lack of feedback mechanisms in the External Quality Assurance
      schemes of sputum smear microscopy render the opportunity for improvement
      difficult; Serial sputum examination showed a considerable rate of positivity in
      the second sputum sample when compared with the others.

PMID- 24885988
TI  - In silico evaluation of the influence of the translocon on partitioning of
      membrane segments.
AB  - BACKGROUND: The locations of the TM segments inside the membrane proteins are the
      consequence of a cascade of several events: the localizing of the nascent chain
      to the membrane, its insertion through the translocon, and the conformation
      adopted to reach its stable state inside the lipid bilayer. Even though the
      hydrophobic h-region of signal peptides and a typical TM segment are both
      composed of mostly hydrophobic side chains, the translocon has the ability to
      determine whether a given segment is to be inserted into the membrane. Our goal
      is to acquire robust biological insights into the influence of the translocon on
      membrane insertion of helices, obtained from the in silico discrimination between
      signal peptides and transmembrane segments of bitopic proteins. Therefore, by
      exploiting this subtle difference, we produce an optimized scale that evaluates
      the tendency of each amino acid to form sequences destined for membrane insertion
      by the translocon. RESULTS: The learning phase of our approach is conducted on
      carefully chosen data and easily converges on an optimal solution called the
      PMIscale (Potential Membrane Insertion scale). Our study leads to two striking
      results. Firstly, with a very simple sliding-window prediction method, PMIscale
      enables an efficient discrimination between signal peptides and signal anchors.
      Secondly, PMIscale is also able to identify TM segments and to localize them
      within protein sequences. CONCLUSIONS: Despite its simplicity, the localization
      method based on PMIscale nearly attains the highest level of TM topography
      prediction accuracy as the current state-of-the-art prediction methods. These
      observations confirm the prominent role of the translocon in the localization of
      TM segments and suggest several biological hypotheses about the physical
      properties of the translocon.

PMID- 24885989
TI  - Systematic analysis of the factors that adversely affect the rate of cell
      accumulation in mouse embryos during their culture in vitro.
AB  - BACKGROUND: Retarded embryo growth is a pervasive effect of culture in vitro.
      METHODS: A systematic analysis of the interactions between media design, embryo
      culture density, oxygen tension, amino acids, trophic ligands and the genetic
      background of the mouse on embryo growth rates in vitro was performed. RESULTS:
      Growth retardation of mouse zygotes was greater in 20% O2 than 5%, a sequential
      media design was superior to static simple media designs, but the supplementation
      of simple media with mixed amino acids mitigated this difference. There was a
      beneficial effect of communal culture in small volumes, and supplementation with
      a trophic ligand (Paf) further enhanced growth rates. For hybrid strain zygotes
      (B6CBF1) communal culture in KSOM media supplemented with amino acids, albumin
      and Paf under 5% O2 resulted in complete rescue of their rate of accumulation of
      cells and blastocyst formation. Inbred strain (C57BL6/J) zygotes, however, still
      showed some retardation of development under these conditions. The additional
      supplementation of media with another trophic ligand (IGF1) showed a further
      additive beneficial effect on development of inbred strain embryos but they still
      showed a growth deficit of ~ 23% cell number. The results show that optimising
      the interactions between a range of culture conditions and media design can
      rescue hybrid strain embryos from a retarded rate of cell proliferation caused by
      culture in vitro, but this was incomplete for the B6 strain. CONCLUSIONS: The
      results indicate that the growth requirement of embryos in vitro varies depending
      upon their genetic background and provide models for the further genetic analysis
      of embryo growth.

PMID- 24885990
TI  - Identification and mapping of stable QTL with main and epistasis effect on rice
      grain yield under upland drought stress.
AB  - BACKGROUND: Drought is one of the most important abiotic stresses that cause
      drastic reduction in rice grain yield (GY) in rainfed environments. The
      identification and introgression of QTL leading to high GY under drought have
      been advocated to be the preferred breeding strategy to improve drought tolerance
      of popular rice varieties. Genetic control of GY under reproductive-stage drought
      stress (RS) was studied in two BC1F4 mapping populations derived from crosses of
      Kali Aus, a drought-tolerant aus cultivar, with high-yielding popular varieties
      MTU1010 and IR64. The aim was to identify QTL for GY under RS that show a large
      and consistent effect for the trait. Bulk segregant analysis (BSA) was used to
      identify significant markers putatively linked with high GY under drought.
      RESULTS: QTL analysis revealed major-effect GY QTL: qDTY1.2, qDTY2.2 and qDTY1.3,
      qDTY2.3 (DTY; Drought grain yield) under drought consistently over two seasons in
      Kali Aus/2*MTU1010 and Kali Aus/2*IR64 populations, respectively. qDTY1.2 and
      qDTY2.2 explained an additive effect of 288 kg ha-1 and 567 kg ha-1 in Kali
      Aus/2*MTU1010, whereas qDTY1.3 and qDTY2.3 explained an additive effect of 198 kg
      ha-1 and 147 kg ha-1 in Kali Aus/2*IR64 populations, respectively.Epistatic
      interaction was observed for DTF (days to flowering) between regions on
      chromosome 2 flanked by markers RM154-RM324 and RM263-RM573 and major epistatic
      QTL for GY showing interaction between genomic locations on chromosome 1 at
      marker interval RM488-RM315 and chromosome 2 at RM324-RM263 in 2012 DS and 2013
      DS RS in Kali Aus/2*IR64 mapping populations. CONCLUSION: The QTL, qDTY1.2,
      qDTY1.3, qDTY2.2, and qDTY2.3, identified in this study can be used to improve GY
      of mega varieties MTU1010 and IR64 under different degrees of severity of drought
      stress through marker-aided backcrossing and provide farmers with improved
      varieties that effectively combine high yield potential with good yield under
      drought. The observed epistatic interaction for GY and DTF will contribute to our
      understanding of the genetic basis of agronomically important traits and enhance
      predictive ability at an individualized level in agriculture.

PMID- 24885991
TI  - Self-reported attitudes and behaviours of medical students in Pakistan regarding
      academic misconduct: a cross-sectional study.
AB  - BACKGROUND: Honesty and integrity are key attributes of an ethically competent
      physician. However, academic misconduct, which includes but is not limited to
      plagiarism, cheating, and falsifying documentation, is common in medical colleges
      across the world. The purpose of this study is to describe differences in the
      self-reported attitudes and behaviours of medical students regarding academic
      misconduct depending on gender, year of study and type of medical institution in
      Pakistan. METHODS: A cross sectional study was conducted with medical students
      from one private and one public sector medical college. A pre-coded questionnaire
      about attitudes and behaviours regarding plagiarism, lying, cheating and
      falsifying documentation was completed anonymously by the students. RESULTS: A
      total of 465 medical students filled the questionnaire. 53% of private medical
      college students reported that they recognize copying an assignment verbatim and
      listing sources as references as wrong compared to 35% of public medical college
      students. 26% of private medical college students self-report this behaviour as
      compared to 42% of public medical college students. 22% of private versus 15% of
      public medical college students and 21% of students in clinical years compared to
      17% in basic science years admit to submitting a fake medical certificate to
      justify an absence. 87% of students at a private medical college believe that
      cheating in an examination is wrong as compared to 66% of public medical college
      students and 24% self-report this behaviour in the former group as compared to
      41% in the latter. 63% of clinical year students identify cheating as wrong
      compared to 89% of their junior colleagues. 71% of male versus 84% of female
      respondents believe that cheating is wrong and 42% of males compared to 23% of
      females admit to cheating. CONCLUSIONS: There are significant differences in
      medical students' attitudes and behaviours towards plagiarism, lying, cheating
      and stealing by gender, seniority status and type of institution. The ability to
      identify acts of academic misconduct does not deter students from engaging in the
      behaviour themselves, as evidenced by self-reporting.

PMID- 24885992
TI  - Potential biases in the classification, analysis and interpretations in cross
      sectional study: commentaries - surrounding the article "resting heart rate: its
      correlations and potential for screening metabolic dysfunctions in adolescents".
AB  - BACKGROUND: Resting heart rate reflects sympathetic nerve activity. A significant
      association between resting heart rate (HR) and all causes of cardiovascular
      mortality has been reported by some epidemiologic studies. Despite suggestive
      evidence, resting heart rate (RHR) has not been formally explored as a prognostic
      factor and potential therapeutic outcome and, therefore, is not generally
      accepted in adolescents. DISCUSSION: The core of the debate is the methodological
      aspects used in "Resting heart rate: its correlations and potential for screening
      metabolic dysfunctions in adolescents"; the points are: cutoff used for cluster
      RHR, two different statistical models used to analyze the same set of variables,
      one for continuous data, and another for categorical data; interpretation of p
      value < 0.05, sampling process involving two random stages, analysis of design
      effect and the parameters of screening tests. SUMMARY: Aspects that must be taken
      into account for evaluation of a screening test to measure the potential for
      discrimination for a common variable (population with outcome vs. no outcome
      population), the main indicators are: sensitivity, specificity, accuracy,
      positive predictive value and negative predictive value. The measures of
      argumentation equality (CI) or difference (p-valor) are important to validate
      these indicators but do not indicate quality of screening.

PMID- 24885993
TI  - A household randomized, controlled trial of the efficacy of 0.03% transfluthrin
      coils alone and in combination with long-lasting insecticidal nets on the
      incidence of Plasmodium falciparum and Plasmodium vivax malaria in Western Yunnan
      Province, China.
AB  - BACKGROUND: Mosquito coils are the most commonly used household insecticidal
      product in the world with sales exceeding 50 billion coils, used by two billion
      people worldwide annually. Despite strong evidence that coils prevent mosquito
      bites a systematic review concluded that there is no evidence that burning
      mosquito coils prevents malaria acquisition. Therefore, the current trial was
      designed to measure and compare prevention of malaria infection by mosquito coils
      or long-lasting insecticidal net (LLIN) or a combination of the two in Yunnan,
      China in the Greater Mekong sub-region. METHODS: A four-arm single blind
      household-randomized design was chosen as coils emanate insecticide throughout
      the household. Households enrolled at baseline were randomly allocated by the
      lottery method to one of the four intervention arms: (i) nothing, (ii) 0.03%
      transfluthrin coils alone, (iii) deltamethrin long-lasting insecticide treated
      nets, (LLINs) alone or (iv) a combination of transfluthrin coils and deltamethrin
      LLINs. All household members were recruited to the study, with only those
      households excluded with pregnant or breastfeeding mothers, members with chest
      complaints or allergies or members that regularly slept away from home. The main
      outcome of interest was Plasmodium falciparum malaria prevalence detected by
      rapid diagnostic tests (RDTs) during six repeated monthly cross-sectional
      surveys. The secondary outcome of interest was the effect on Plasmodium vivax
      prevalence detected in the same way. RESULTS: A total of 2,052 households were
      recruited into the study, comprising 7,341 individuals The odds ratios of testing
      positive by RDT with P. falciparum or P. vivax were >75% lower for all
      intervention arms compared with the control arm. Coils alone provided 77%
      protection (95% CI: 50%-89%), LLINs provided 91% protection (95% CI: 72%-97%) and
      the combination of coils and LLINs provided 94% protection (95% CI: 77%-99%)
      against P. falciparum compared with the control arm. There was no statistically
      significant difference between the protective efficacies of the different
      interventions. CONCLUSIONS: This is the first robust clinical evaluation of
      transfluthrin mosquito coils as a means to reduce malaria and the high degree of
      infection prevented would indicate they represent a potentially highly effective
      tool, which could be integrated into larger vector control programmes. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT00442442, March 2007.

PMID- 24885994
TI  - Interfacial film stabilized W/O/W nano multiple emulsions loaded with green tea
      and lotus extracts: systematic characterization of physicochemical properties and
      shelf-storage stability.
AB  - BACKGROUND AND AIMS: Multiple emulsions have excellent encapsulating potential
      and this investigation has been aimed to encapsulate two different plant extracts
      as functional cosmetic agents in the W/O/W multiple emulsions and the resultant
      system's long term stability has been determined in the presence of a thickener,
      hydroxypropyl methylcellulose (HPMC). METHODS: Multiple W/O/W emulsions have been
      generated using cetyl dimethicone copolyol as lipophilic emulsifier and a blend
      of polyoxyethylene (20) cetyl ether and cetomacrogol 1000(r) as hydrophilic
      emulsifiers. The generated multiple emulsions have been characterized with
      conductivity, pH, microscopic analysis, phase separation and rheology for a
      period of 30 days. Moreover, long term shelf-storage stability has been tested to
      understand the shelf-life by keeping the generated multiple emulsion formulations
      at 25 +/- 10 degrees C and at 40 +/- 10% relative humidity for a period of 12
      months. RESULTS: It has been observed that the hydrophilic emulsifiers and HPMC
      have considerably improved the stability of multiple emulsions for the followed
      period of 12 months at different storage conditions. These multiple emulsions
      have shown improved entrapment efficiencies concluded on the release rate of
      conductometric tracer entrapped in the inner aqueous phase of the multiple
      emulsions. CONCLUSION: Multiple emulsions have been found to be stable for a
      longer period of time with promising characteristics. Hence, stable multiple
      emulsions loaded with green tea and lotus extracts could be explored for their
      cosmetic benefits.

PMID- 24885995
TI  - A mammary adenocarcinoma murine model suitable for the study of cancer
      immunoediting.
AB  - BACKGROUND: Cancer immunoediting is a dynamic process composed of three phases:
      elimination (EL), equilibrium (EQ) and escape (ES) that encompasses the potential
      host-protective and tumor-sculpting functions of the immune system throughout
      tumor development. Animal models are useful tools for studying diseases such as
      cancer. The present study was designed to characterize the interaction between
      mammary adenocarcinoma M-406 and CBi, CBi- and CBi/L inbred mice lines. RESULTS:
      The mammary adenocarcinoma M-406 developed spontaneously in a CBi mouse. CBi/L
      and CBi- mice were artificially selected for body conformation from CBi. When CBi
      mice are s.c. challenged with M-406, tumor growths exponentially in 100% of
      animals, while in CBi- the tumor growths briefly and then begins a rejection
      process in 100% of the animals. In CBi/L the growth of the tumor shows the three
      phases: 51.6% in ES, 18.5% in EQ and 29.8% in EL. CONCLUSIONS: The results
      obtained support the conclusion that the system M-406 plus the inbred mouse lines
      CBi, CBi- and CBi/L, is a good murine model to study the process of tumor
      immunoediting.

PMID- 24885996
TI  - Rapid diagnostic tests for malaria and health workers' adherence to test results
      at health facilities in Zambia.
AB  - BACKGROUND: In Zambia, there has been a large scaling up of interventions to
      control malaria in recent years including the deployment of rapid diagnostic
      tests (RDTs) to improve malaria surveillance data as well as guide malaria
      treatment in health facilities. The practical challenge is the impact of RDT
      results on subsequent management of patients. This study explored the role of
      RDTs in malaria diagnosis and the health workers' adherence to test results.
      METHODS: An observational prospective study was carried out at health centres in
      four districts, namely Chibombo, Chingola, Chipata, and Choma. Children under the
      age of five years with history of fever were recruited and the clinicians' use of
      RDT results was observed to establish whether prescriptions were issued prior to
      the availability of parasitological results or after, and whether RDT results
      influenced their prescriptions. RESULTS: Of the 2, 393 recruited children, 2, 264
      had both RDT and microscopic results. Two in three (68.6%) children were treated
      with anti-malarials despite negative RDT results and almost half (46.2%) of these
      were prescribed Coartem(r). Only 465 (19.4%) of the 2,393 children were
      prescribed drugs before receiving laboratory results. A total of 76.5% children
      were prescribed drugs after laboratory results. Children with RDT positive
      results were 2.66 (95% CI (2.00, 3.55)) times more likely to be prescribed anti
      malarial drugs. Children who presented with fever at admission (although history
      of fever or presence of fever at admission was an entry criterion) were 42% less
      likely to be prescribed an anti-malarial drug compared to children who had no
      fever (AOR = 0.58; 95% CI (0.52, 0.65)). It was noted that proportions of
      children who were RDT- and microscopy-positive significantly declined over the
      years from 2005 to 2008. CONCLUSIONS: RDTs may contribute to treatment of febrile
      illness by confirming malaria cases from non-malaria cases in children under the
      age of five. However, the adherence of the health workers to prescribing anti
      malarials to only RDT-positive cases at health facility level will still require
      to be explored further as their role is crucial in more precise reporting of
      malaria cases in this era towards malaria elimination as the target.

PMID- 24885997
TI  - In vitro study of the replication capacity of the RGNNV and the SJNNV
      betanodavirus genotypes and their natural reassortants in response to
      temperature.
AB  - Betanodaviruses are the causative agents of viral nervous necrosis and affect a
      broad range of fish species worldwide. Their bi-segmented genome is composed of
      the RNA1 and the RNA2 molecules encoding the viral polymerase and the coat
      protein, respectively. In southern Europe the presence of the RGNNV and the SJNNV
      genotypes, and the RGNNV/SJNNV and RGNNV/SJNNV reassortants has been documented.
      Several studies have reported a correlation between water temperature and disease
      onset. To explore the replication efficiency of betanodaviruses with different
      genomes in relation to temperature and to understand the role of genetic
      reassortment on viral phenotype, RGNNV, SJNNV, RGNNV/SJNNV and RGNNV/SJNNV field
      isolates were fully sequenced, and growth curves generated in vitro at four
      different temperatures (15, 20, 25, 30  degrees C) were developed for each
      isolate. The data obtained, corroborated by statistical analysis, demonstrated
      that viral titres of diverse betanodavirus genotypes varied significantly in
      relation to the incubation temperature of the culture. In particular, at 30 
      degrees C betanodaviruses under investigation presented different phenotypes, and
      viruses containing the RNA1 of the RGNNV genotype showed the best replication
      efficiency. Laboratory results demonstrated that viruses clustering within the
      same genotype based on the polymerase gene, possess similar growth kinetics in
      response to temperature, thus highlighting the key role of RNA1 in controlling
      viral replication at different environmental conditions. The results generated
      might have practical implications for the inference of viral phenotype according
      to genetic features and may contribute to a better understanding of betanodavirus
      ecology.

PMID- 24885998
TI  - Who are the under- and never-screened for cancer in Ontario: a qualitative
      investigation.
AB  - BACKGROUND: Observed breast, cervical and colon cancer screening rates are below
      provincial targets for the province of Ontario, Canada. The populations who are
      under- or never-screened for these cancers have not been described at the Ontario
      provincial level. Our objective was to use qualitative methods of inquiry to
      explore who are the never- or under-screened populations of Ontario. METHODS:
      Qualitative data were collected from two rounds of focus group discussions
      conducted in four communities selected using maps of screening rates by
      dissemination area. The communities selected were archetypical of the Ontario
      context: urban, suburban, small city and rural. The first phase of focus groups
      was with health service providers. The second phase of focus groups was with
      community members from the under- and never-screened population. Guided by a
      grounded theory methodology, data were collected and analyzed simultaneously to
      enable the core and related concepts about the under- and never-screened to
      emerge. RESULTS: The core concept that emerged from the data is that the under-
      and never-screened populations of Ontario are characterized by diversity. Group
      level characteristics of the under- and never-screened included: 1) the uninsured
      (e.g., Old Order Mennonites and illegal immigrants); 2) sexual abuse survivors;
      3) people in crisis; 4) immigrants; 5) men; and 6) individuals accessing
      traditional, alternative and complementary medicine for health and wellness.
      Under- and never-screened could have one or multiple group characteristics.
      CONCLUSION: The under- and never-screened in Ontario comprise a diversity of
      groups. Heterogeneity within and intersectionality among under- and never
      screened groups adds complexity to cancer screening participation and program
      planning.

PMID- 24886000
TI  - Genetic species identification and population structure of Halophila
      (Hydrocharitaceae) from the Western Pacific to the Eastern Indian Ocean.
AB  - BACKGROUND: The Indo-Pacific region has the largest number of seagrass species
      worldwide and this region is considered as the origin of the Hydrocharitaceae.
      Halophila ovalis and its closely-related species belonging to the
      Hydrocharitaceae are well-known as a complex taxonomic challenge mainly due to
      their high morphological plasticity. The relationship of genetic differentiation
      and geographic barriers of H. ovalis radiation was not much studied in this
      region. Are there misidentifications between H. ovalis and its closely related
      species? Does any taxonomic uncertainty among different populations of H. ovalis
      persist? Is there any genetic differentiation among populations in the Western
      Pacific and the Eastern Indian Ocean, which are separated by the Thai-Malay
      peninsula? Genetic markers can be used to characterize and identify individuals
      or species and will be used to answer these questions. RESULTS: Phylogenetic
      analyses of the nuclear ribosomal internal transcribed spacer region based on
      materials collected from 17 populations in the Western Pacific and the Eastern
      Indian Ocean showed that some specimens identified as H. ovalis belonged to the
      H. major clade, also supported by morphological data. Evolutionary divergence
      between the two clades is between 0.033 and 0.038, much higher than the
      evolutionary divergence among H. ovalis populations. Eight haplotypes were found;
      none of the haplotypes from the Western Pacific is found in India and vice versa.
      Analysis of genetic diversity based on microsatellite analysis revealed that the
      genetic diversity in the Western Pacific is higher than in the Eastern Indian
      Ocean. The unrooted neighbor-joining tree among 14 populations from the Western
      Pacific and the Eastern Indian Ocean showed six groups. The Mantel test results
      revealed a significant correlation between genetic and geographic distances among
      populations. Results from band-based and allele frequency-based approaches from
      Amplified Fragment Length Polymorphism showed that all samples collected from
      both sides of the Thai-Malay peninsula were clustered into two clades: Gulf of
      Thailand and Andaman Sea. CONCLUSIONS: Our study documented the new records of H.
      major for Malaysia and Myanmar. The study also revealed that the Thai-Malay
      peninsula is a geographic barrier between H. ovalis populations in the Western
      Pacific and the Eastern Indian Ocean.

PMID- 24885999
TI  - PM2.5-induced cardiovascular dysregulation in rats is associated with elemental
      carbon and temperature-resolved carbon subfractions.
AB  - BACKGROUND: We tested the hypothesis that cardiovascular responses to PM2.5
      exposure will be enhanced in hypertensive rats and linked to specific
      carbonaceous pollutants in an urban industrial setting. METHODS: Spontaneously
      hypertensive rats were exposed by inhalation to concentrated PM2.5 in an
      industrial area of Dearborn, Michigan, for four consecutive summer days. Blood
      pressure (BP), heart rate (HR) and HR variability (HRV) metrics (SDNN, RMSSD)
      were assessed by radiotelemetry and compared to 1 h- and 8 h-averaged
      fluctuations in PM2.5 composition, with a focus on elemental and organic carbon
      (EC and OC, respectively), and temperature-resolved subfractions (EC1-EC5, PC
      (pyrolized carbon), and OC1-OC4), as well as other major and minor PM components.
      RESULTS: Mean HR and BP were increased, while HRV was decreased over 4 days of
      exposure. Using 1 h averages, EC (1 MUg/m3 increase) was associated with
      increased HR of 11-32 bpm (4-11% increase), 1.2-1.5 ms (22-27%) decreases in
      SDNN, 3-14 mmHg (1.5-8%) increases in systolic BP, and 5-12 mmHg (4-9%) increases
      in diastolic BP. By comparison, associations with OC were negligible. Using 8 h
      averages, EC subfractions were linked with increased heart rate (EC1: 13 bpm;
      EC2, EC3, PC: <5 bpm) and SDNN (EC1> > EC2 > EC3, EC4, PC), but with decreased
      RMSSD (EC2, EC5 > EC3, EC4). Minimal effects were associated with OC and OC1.
      Associations between carbon subfractions and BP were negligible. Associations
      with non-carbonaceous components and trace elements were generally non
      significant or of negligible effect size. CONCLUSIONS: These findings are the
      first to describe associations between acute cardiovascular responses and
      thermally resolved carbon subfractions. We report that cardiovascular responses
      to PM2.5 carbonaceous materials appear to be driven by EC and its EC1 fraction.

PMID- 24886001
TI  - RNA-seq based SNPs for mapping in Brassica juncea (AABB): synteny analysis
      between the two constituent genomes A (from B. rapa) and B (from B. nigra) shows
      highly divergent gene block arrangement and unique block fragmentation patterns.
AB  - BACKGROUND: Brassica juncea (AABB) is an allotetraploid species containing
      genomes of B. rapa (AA) and B. nigra (BB). It is a major oilseed crop in South
      Asia, and grown on approximately 6-7 million hectares of land in India during the
      winter season under dryland conditions. B. juncea has two well defined gene pools
      -Indian and east European. Hybrids between the two gene pools are heterotic for
      yield. A large number of qualitative and quantitative traits need to be
      introgressed from one gene pool into the other. This study explores the
      availability of SNPs in RNA-seq generated contigs, and their use for general
      mapping, fine mapping of selected regions, and comparative arrangement of gene
      blocks on B. juncea A and B genomes. RESULTS: RNA isolated from two lines of B.
      juncea--Varuna (Indian type) and Heera (east European type)--was sequenced using
      Illumina paired end sequencing technology, and assembled using the Velvet de novo
      programme. A and B genome specific contigs were identified in two steps. First,
      by aligning contigs against the B. rapa protein database (available at BRAD), and
      second by comparing percentage identity at the nucleotide level with B. rapa CDS
      and B. nigra transcriptome. 135,693 SNPs were recorded in the assembled partial
      gene models of Varuna and Heera, 85,473 in the A genome and 50,236 in the B.
      Using KASpar technology, 999 markers were added to an earlier intron polymorphism
      marker based map of a B. juncea Varuna x Heera DH population. Many new gene
      blocks were identified in the B genome. A number of SNP markers covered single
      copy homoeologues of the A and B genomes, and these were used to identify
      homoeologous blocks between the two genomes. Comparison of the block architecture
      of A and B genomes revealed extensive differences in gene block associations and
      block fragmentation patterns. CONCLUSIONS: Sufficient SNP markers are available
      for general and specific -region fine mapping of crosses between lines of two
      diverse B. juncea gene pools. Comparative gene block arrangement and block
      fragmentation patterns between A and B genomes support the hypothesis that the
      two genomes evolved from independent hexaploidy events.

PMID- 24886002
TI  - Bidirectional relationships between trauma exposure and posttraumatic stress: a
      longitudinal study of Detroit residents.
AB  - Previous research has documented bidirectional relationships between trauma
      exposure and posttraumatic stress (PTS), such that individuals who are exposed to
      more traumatic events are at increased risk of developing PTS, and more severe
      PTS is associated with more subsequent trauma exposure. However, the empirical
      literature is limited by a lack of longitudinal studies that include continuous
      measures of PTS, differentiate between assaultive (e.g., sexual assault, being
      held up or mugged) and nonassaultive (e.g., serious illness, natural disaster)
      trauma, and focus on urban contexts. The purpose of this study was to fill these
      gaps through testing 3-wave cross-lagged panel models of exposure to assaultive
      and nonassaultive traumatic events and PTS among a large sample of urban-dwelling
      adults (N = 1,360; 84.4% non-Hispanic Black). In the model including assaultive
      trauma, more Wave 2 assaultive events were associated with significantly higher
      Wave 3 PTS. In contrast, in the model including nonassaultive trauma, higher Wave
      1 and Wave 2 PTS were associated with more nonassaultive events at Waves 2 and 3,
      respectively. Taken together, the findings suggest a cycle of adversity wherein
      urban residents who have experienced assaultive trauma are at risk of more severe
      PTS, which in turn increases risk for exposure to nonassaultive trauma. This
      cycle could be tested directly in future studies through models including both
      types of events. Additional research on the mechanisms that underlie the pathways
      between PTS and traumatic events could also have implications for policy and
      practice.

PMID- 24886004
TI  - Major depression in mothers predicts reduced ventral striatum activation in
      adolescent female offspring with and without depression.
AB  - Prior research has identified reduced reward-related brain activation as a
      promising endophenotype for the early identification of adolescents with major
      depressive disorder (MDD). However, it is unclear whether reduced reward-related
      brain activation constitutes a true vulnerability for MDD. One way of studying
      vulnerability is through a high-risk design. Therefore, the aim of the current
      study was to determine whether reward-related activation of the ventral striatum
      is reduced in nondepressed daughters of mothers with a history of MDD (high-risk)
      similarly to currently depressed adolescent girls, compared with healthy
      controls. By directly comparing groups with a shared risk profile during
      differing states, we aimed to shed light on the endophenotypic nature of reduced
      reward processing for adolescent depression. We compared reward-related neural
      activity through functional magnetic resonance imaging (fMRI) between three
      groups of female biological offspring (N = 52) of mothers with differential MDD
      status: (a) currently depressed daughters of mothers with a history of MDD (MDD
      group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed
      daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age
      and SES-matched control daughters of mothers with no past or current
      psychopathology in either the mother or the daughter (healthy control group; n =
      19). For the outcome phase of the reward task, right-sided ventral striatum
      activation was reduced for both currently depressed and high-risk girls compared
      with healthy controls. This ventral striatal activity correlated significantly
      with maternal depression scores. These findings provide further evidence of
      aberrant functioning for the United States Department of Health & Human Services,
      National Institutes of Health, National Institute of Mental Health (NIMH)
      Research Domain Criteria (RDoC)-defined domain of positive valence systems as a
      vulnerability factor for MDD and a potential endophenotype for the development of
      depression.

PMID- 24886003
TI  - Neural reactivity to rewards and losses in offspring of mothers and fathers with
      histories of depressive and anxiety disorders.
AB  - Depression appears to be characterized by reduced neural reactivity to receipt of
      reward. Despite evidence of shared etiologies and high rates of comorbidity
      between depression and anxiety, this abnormality may be relatively specific to
      depression. However, it is unclear whether children at risk for depression also
      exhibit abnormal reward responding, and if so, whether risk for anxiety moderates
      this association. The feedback negativity (FN) is an event-related potential
      component sensitive to receipt of rewards versus losses that is reduced in
      depression. Using a large community sample (N = 407) of 9-year-old children who
      had never experienced a depressive episode, we examined whether histories of
      depression and anxiety in their parents were associated with the FN following
      monetary rewards and losses. Results indicated that maternal history of
      depression was associated with a blunted FN in offspring, but only when there was
      no maternal history of anxiety. In addition, greater severity of maternal
      depression was associated with greater blunting of the FN in children. No effects
      of paternal psychopathology were observed. Results suggest that blunted
      reactivity to rewards versus losses may be a vulnerability marker that is
      specific to pure depression, but is not evident when there is also familial risk
      for anxiety. In addition, these findings suggest that abnormal reward responding
      is evident as early as middle childhood, several years prior to the sharp
      increase in the prevalence of depression and rapid changes in neural reward
      circuitry in adolescence.

PMID- 24886006
TI  - Acquisition of behavioral avoidance: task-irrelevant conditioned stimuli trigger
      costly decisions.
AB  - Individuals avoid stimuli which are associated with aversive experience to
      preserve safety. However, behavioral avoidance also causes impairments and
      prevents the individual from attaining positive rewards. Little is known about
      the link between fear acquisition and the development of behavioral avoidance in
      the presence of potential rewards. Therefore, two experiments investigated the
      impact of fear conditioning on a subsequent gambling task. In an experimental
      group (n = 30) advantageous choices (higher reward probability) were linked to a
      fear-relevant stimulus that was associated with an aversive unconditioned
      stimulus (US) during fear conditioning (conditioned stimulus, CS+). A
      disadvantageous choice (lower reward probability) was, however, linked to a safe
      stimulus that was never associated with the US (CS-). In a control group (n =
      25), fear conditioning was followed by a similar gambling task with novel
      stimuli. A second experiment focused on individual predictors of avoidant
      decisions (n = 81). Compared with the control group, individuals in the
      experimental groups avoided the advantageous CS + choice despite fewer gains. The
      predictor analysis further clarified that avoidant decisions were pronounced in
      highly trait anxious participants who exhibited higher fear responses. On the
      other hand, findings also indicated a reduction in absolute avoidance across the
      task. Combined, these findings demonstrate that fear conditioning can lead to
      avoidant decision making, especially in vulnerable individuals. The resulting
      costs parallel impairments caused by behavioral avoidance. Such an emotional
      decision-making style may be a link between aversive experience and the
      development of habitual pathological avoidance. Introducing rewards for approach,
      however, may counteract avoidant decisions.

PMID- 24886005
TI  - Reward function: a promising but (still) underexamined dimension in developmental
      psychopathology.
AB  - The goal of this Special Section is to explore the ways that investigation of
      reward function can shed light on the development and pathophysiology of
      psychopathology. Reward function provides a promising starting point for clinical
      affective neuroscience research because, thanks to the extensive literature on
      the neural mechanisms of addiction, the functional neuroanatomy, cellular
      mechanisms, and genetic contributions to reward circuitry have been well
      delineated (see Russo & Nestler, 2013, for details).

PMID- 24886007
TI  - Are attentional control resources reduced by worry in generalized anxiety
      disorder?
AB  - This is the first study to examine attentional control capacities in generalized
      anxiety disorder (GAD). GAD is characterized by uncontrollable worry. Individuals
      diagnosed with GAD and healthy participants (HPs) performed a random key-pressing
      task while thinking about a worrisome or a positive future event, to assess the
      extent to which attentional control resources are used by worry. Attentional
      control was also assessed when participants were not instructed to think about a
      specific topic using the N-back task, which varies in task difficulty, and
      therefore is sensitive to subtle differences in ability to handle increasing
      demands on attentional control within the same paradigm. GAD participants (but
      not HPs) were less random while worrying than thinking about a positive event
      during the key-pressing task, suggesting that worry consumed more attentional
      control resources in this population. During the N-Back task, GAD participants
      performed worse than HPs during the high load conditions only, indicating greater
      difficulty in sustaining focus on conditions requiring a higher degree of
      attentional control, even without concurrent task activity. Poor attentional
      control might underpin the difficulty of GAD individuals to stop worrying and
      switch to thinking more benign information. Further research could investigate
      whether worry consumes attentional control resources in other psychological
      disorders with high rates of worry (e.g., panic disorder, psychosis), as well as
      the extent to which attentional control is used by other forms of repetitive
      thinking, such as depressive rumination.

PMID- 24886008
TI  - Peer victimization (and harsh parenting) as developmental correlates of cognitive
      reactivity, a diathesis for depression.
AB  - Prior research has shown cognitive reactivity to be a diathesis for depression.
      Seeking evidence for the developmental origins of such diatheses, the current
      study examined peer victimization and harsh parenting as developmental correlates
      of cognitive reactivity in 571 children and adolescents (ages 8-13 years). Four
      major findings emerged. First, a new method for assessing cognitive reactivity in
      children and adolescents showed significant reliability and demonstrated
      construct validity vis-a-vis its relation to depression. Second, history of more
      severe peer victimization was significantly related to cognitive reactivity, with
      verbal victimization being more strongly tied to cognitive reactivity than other
      subtypes of peer victimization. Third, harsh parenting was also significantly
      related to cognitive reactivity. Fourth, both peer victimization and harsh
      parenting made unique statistical contributions to cognitive reactivity, after
      controlling for the effects of the other. Taken together, these findings provide
      preliminary support for a developmental model pertaining to origins of cognitive
      reactivity in children and adolescents.

PMID- 24886009
TI  - Faces, feelings, words: divergence across channels of emotional responding in
      complicated grief.
AB  - Recent evidence suggests that the inability to respond in a context appropriate
      manner earlier in bereavement is predictive of a protracted grief course with
      poorer adjustment following the loss (Coifman & Bonanno, 2010). However, little
      is known about the emotional behavior of adults later in bereavement and whether
      emotional responding becomes dsyregulated across other channels. An impressive
      body of evidence in the schizophrenia literature demonstrates a marked
      disconnection between observable displays of emotion and experienced affect
      within individuals diagnosed with schizophrenia (e.g., Kring & Moran, 2008). On
      the basis of this influential work, we examined the emotional responses of a
      sample of bereaved adults who lost a spouse 1.5-3 years previously. One bereaved
      group had complicated grief (CG) and the other was relatively asymptomatic. We
      used an idiographic task where participants discussed their relationships with
      their spouse and current attachment figure in contexts of conflict and intimacy.
      We measured emotional responses across 3 channels: self-reported affect, facial
      expressions, and emotional word use. Individuals within the CG group were less
      facially expressive across contexts than the asymptomatic group but in some
      contexts reported experiencing greater affect and used more negative emotion
      words. These findings suggest that complicated grief in later bereavement is
      characterized by a disassociation between emotional responding across channels,
      with context insensitive responding, restricted to facial displays of emotion.

PMID- 24886013
TI  - Clinician judgments of clinical utility: A comparison of DSM-IV-TR personality
      disorders and the alternative model for DSM-5 personality disorders.
AB  - This study compared the perceived clinical utility of DSM-IV-TR personality
      disorder diagnoses (retained in DSM-5) with the alternative model presented in
      DSM-5 Section III, using a national sample of clinicians applying both systems to
      their own patients. A sample of 337 mental health clinicians (26% psychiatrists,
      63% psychologists, and 11% other professional disciplines) provided a complete
      assessment of all personality disorder features listed in DSM-IV-TR and DSM-5
      Section III. After applying each diagnostic model, clinicians evaluated the
      clinical utility of that model with respect to communication with patients and
      with other professionals, comprehensiveness, descriptiveness, ease of use, and
      utility for treatment planning. These perceptions were compared across DSM-IV-TR
      and the 3 components of the DSM-5 Section III model, and between psychiatrists
      and nonpsychiatrists. Although DSM-IV-TR was seen as easy to use and useful for
      professional communication, in every other respect the DSM-5 Section III model
      was viewed as being equally or more clinically useful than DSM-IV-TR. In
      particular, the DSM-5 dimensional trait model was seen as more useful than DSM-IV
      TR in 5 of 6 comparisons-by psychiatrists as well as other professionals.
      Although concerns were expressed about the clinical utility of the DSM-5
      personality disorder system during its development, these criticisms were offered
      without data on the proposed system. The results of this study demonstrate that
      aside from the current familiarity of the DSM-IV-TR approach, it offers little
      advantage in perceived clinical utility over the DSM-5 Section III system,
      whereas the latter is viewed as being more useful in several respects.

PMID- 24886011
TI  - Anhedonia and the relative reward value of drug and nondrug reinforcers in
      cigarette smokers.
AB  - Anhedonia-a psychopathologic trait indicative of diminished interest, pleasure,
      and enjoyment-has been linked to use of and addiction to several substances,
      including tobacco. We hypothesized that anhedonic drug users develop an imbalance
      in the relative reward value of drug versus nondrug reinforcers, which could
      maintain drug use behavior. To test this hypothesis, we examined whether
      anhedonia predicted the tendency to choose an immediate drug reward (i.e.,
      smoking) over a less immediate nondrug reward (i.e., money) in a laboratory study
      of non-treatment-seeking adult cigarette smokers. Participants (N = 275, >=10
      cigarettes/day) attended a baseline visit that involved anhedonia assessment
      followed by 2 counterbalanced experimental visits: (a) after 16-hr smoking
      abstinence and (b) nonabstinent. At both experimental visits, participants
      completed self-report measures of mood state followed by a behavioral smoking
      task, which measured 2 aspects of the relative reward value of smoking versus
      money: (1) latency to initiate smoking when delaying smoking was monetarily
      rewarded and (2) willingness to purchase individual cigarettes. Results indicated
      that higher anhedonia predicted quicker smoking initiation and more cigarettes
      purchased. These relations were partially mediated by low positive and high
      negative mood states assessed immediately prior to the smoking task. Abstinence
      amplified the extent to which anhedonia predicted cigarette consumption among
      those who responded to the abstinence manipulation, but not the entire sample.
      Anhedonia may bias motivation toward smoking over alternative reinforcers,
      perhaps by giving rise to poor acute mood states. An imbalance in the reward
      value assigned to drug versus nondrug reinforcers may link anhedonia-related
      psychopathology to drug use.

PMID- 24886010
TI  - The role of early childhood ADHD and subsequent CD in the initiation and
      escalation of adolescent cigarette, alcohol, and marijuana use.
AB  - Adolescents with attention deficit/hyperactivity disorder (ADHD) are at an
      increased risk for substance use but the pathways through which this risk emerges
      are insufficiently understood. Tobacco, alcohol, and marijuana outcomes were
      compared between adolescents diagnosed with ADHD in early childhood (N = 113) and
      demographically similar controls (N = 65). Participants were assessed from age 5
      until age 18. A comprehensive history of adolescent substance use was compiled
      for each participant and growth in ADHD and conduct disorder (CD) were modeled as
      they related to substance use outcomes. Results indicated that when compared with
      controls, adolescents with ADHD were more likely to try cigarettes, initiate
      alcohol use at early ages, and smoke marijuana more frequently. Furthermore,
      adolescents with ADHD were 4 to 5 times more likely than controls to escalate to
      heavy cigarette and marijuana use after trying these substances once. Adolescents
      with ADHD who escalated to heavy use patterns were more likely to display early
      cigarette use and marked problems with family members, but displayed fewer peer
      problems. There was evidence of baseline effects (latent intercept, measured at
      age 5) for both ADHD and CD on substance use outcomes. Furthermore, growth in
      ADHD symptoms accounted for much of the growth in CD symptoms, and consequently,
      escalating CD symptoms in childhood (latent slope) were viewed as a mediator of
      the relationship between ADHD and cigarette and marijuana use. Maternal drinking
      in early childhood was the strongest predictor of early adolescent alcohol use.
      These findings are discussed with respect to the role of ADHD in the development
      of adolescent risk outcomes.

PMID- 24886012
TI  - Effort, anhedonia, and function in schizophrenia: reduced effort allocation
      predicts amotivation and functional impairment.
AB  - One of the most debilitating aspects of schizophrenia is an apparent interest in
      or ability to exert effort for rewards. Such "negative symptoms" may prevent
      individuals from obtaining potentially beneficial outcomes in educational,
      occupational, or social domains. In animal models, dopamine abnormalities
      decrease willingness to work for rewards, implicating dopamine (DA) function as a
      candidate substrate for negative symptoms given that schizophrenia involves
      dysregulation of the dopamine system. We used the effort-expenditure for rewards
      task (EEfRT) to assess the degree to which individuals with schizophrenia were
      wiling to exert increased effort for either larger magnitude rewards or for
      rewards that were more probable. Fifty-nine individuals with schizophrenia and 39
      demographically similar controls performed the EEfRT task, which involves making
      choices between "easy" and "hard" tasks to earn potential rewards. Individuals
      with schizophrenia showed less of an increase in effort allocation as either
      reward magnitude or probability increased. In controls, the frequency of choosing
      the hard task in high reward magnitude and probability conditions was negatively
      correlated with depression severity and anhedonia. In schizophrenia, fewer hard
      task choices were associated with more severe negative symptoms and worse
      community and work function as assessed by a caretaker. Consistent with patterns
      of disrupted dopamine functioning observed in animal models of schizophrenia,
      these results suggest that 1 mechanism contributing to impaired function and
      motivational drive in schizophrenia may be a reduced allocation of greater effort
      for higher magnitude or higher probability rewards.

PMID- 24886014
TI  - Sex differences in the etiology of psychopathic traits in youth.
AB  - Few studies have examined the etiology of psychopathic traits in youth, and even
      fewer have tested whether the genetic and environmental influences underlying
      these traits differ for boys and girls. We tested for sex differences in the
      etiology of 3 trait dimensions-impulsivity, narcissism, and callous
      unemotionality (CU)-previously found to underlie youth psychopathy in our sample.
      Using biometric modeling we tested whether constraining the genetic and
      environmental influences for each dimension across sex reduced model fit. We also
      tested for qualitative sex differences in the influences underlying these
      dimensions by allowing the genetic and environmental correlations between
      opposite sex dizygotic twins to be less than their respective values in same-sex
      dizygotic twins. Although the magnitudes of the genetic and environmental
      influences underlying the CU and narcissistic trait dimensions did not differ for
      boys and girls, nonshared environmental influences contributed significantly
      greater variance to impulsive traits in boys. No qualitative sex differences were
      found in the influences underlying any of the 3 trait dimensions, suggesting that
      the same genes and environments contribute to these psychopathic traits in males
      and females.

PMID- 24886015
TI  - When or why does perfectionism translate into eating disorder pathology? A
      longitudinal examination of the moderating and mediating role of body
      dissatisfaction.
AB  - Although research has shown that perfectionism is associated with eating disorder
      pathology, the role of body dissatisfaction in this association is less clear. In
      this study, we examined the possible moderating and mediating role of body
      dissatisfaction in the relation between perfectionism and increases in eating
      disorder pathology. Both possible roles were tested in a sample of 455 adolescent
      girls (mean age = 13.25 years) using a 3-wave longitudinal study. We only found
      support for the moderation hypothesis, with girls high on both perfectionism and
      body dissatisfaction exhibiting the highest levels of eating disorder symptoms.
      Implications of these findings are discussed.

PMID- 24886016
TI  - Autobiographical memory specificity in dissociative identity disorder.
AB  - A lack of adequate access to autobiographical knowledge has been related to
      psychopathology. More specifically, patients suffering from depression or a
      history of trauma have been found to be characterized by overgeneral memory, in
      other words, they show a relative difficulty in retrieving a specific event from
      memory located in time and place. Previous studies of overgeneral memory have not
      included patients with dissociative disorders. These patients are interesting to
      consider, as they are hypothesized to have the ability to selectively
      compartmentalize information linked to negative emotions. This study examined
      avoidance and overgeneral memory in patients with dissociative identity disorder
      (DID; n = 12). The patients completed the autobiographical memory test (AMT).
      Their performance was compared with control groups of posttraumatic stress
      disorder (PTSD) patients (n = 26), healthy controls (n = 29), and DID simulators
      (n = 26). Specifically, we compared the performance of separate identity states
      in DID hypothesized to diverge in the use of avoidance as a coping strategy to
      deal with negative affect. No significant differences in memory specificity were
      found between the separate identities in DID. Irrespective of identity state, DID
      patients were characterized by a lack of memory specificity, which was similar to
      the lack of memory specificity found in PTSD patients. The converging results for
      DID and PTSD patients add empirical evidence for the role of overgeneral memory
      involved in the maintenance of posttraumatic psychopathology.

PMID- 24886017
TI  - Quantifying heterogeneity attributable to polythetic diagnostic criteria:
      theoretical framework and empirical application.
AB  - Heterogeneity within psychiatric disorders is both theoretically and practically
      problematic: For many disorders, it is possible for 2 individuals to share very
      few or even no symptoms in common yet share the same diagnosis. Polythetic
      diagnostic criteria have long been recognized to contribute to this
      heterogeneity, yet no unified theoretical understanding of the coherence of
      symptom criteria sets currently exists. A general framework for analyzing the
      logical and mathematical structure, coherence, and diversity of Diagnostic and
      Statistical Manual diagnostic categories (DSM-5 and DSM-IV-TR) is proposed,
      drawing from combinatorial mathematics, set theory, and information theory.
      Theoretical application of this framework to 18 diagnostic categories indicates
      that in most categories, 2 individuals with the same diagnosis may share no
      symptoms in common, and that any 2 theoretically possible symptom combinations
      will share on average less than half their symptoms. Application of this
      framework to 2 large empirical datasets indicates that patients who meet symptom
      criteria for major depressive disorder and posttraumatic stress disorder tend to
      share approximately three-fifths of symptoms in common. For both disorders in
      each of the datasets, pairs of individuals who shared no common symptoms were
      observed. Any 2 individuals with either diagnosis were unlikely to exhibit
      identical symptomatology. The theoretical and empirical results stemming from
      this approach have substantive implications for etiological research into, and
      measurement of, psychiatric disorders.

PMID- 24886018
TI  - Low implicit and explicit aversion toward self-cutting stimuli longitudinally
      predict nonsuicidal self-injury.
AB  - There is a pressing need to improve the ability to identify individuals at risk
      for nonsuicidal self-injury (NSSI; e.g., cutting or burning oneself);
      unfortunately, beyond prior NSSI, there are few powerful longitudinal predictors
      of NSSI. The present study addressed this limitation by investigating the ability
      of a novel factor--low aversion to self-cutting stimuli--to longitudinally
      predict NSSI in 49 individuals with a history of self-cutting. Results revealed
      that both low implicit and explicit aversion to self-cutting stimuli were
      significantly associated with future NSSI (rs = .32-.51), and that these
      associations were unique from several other theoretically important predictors,
      including prior NSSI, number of NSSI methods, implicit identification with self
      cutting, self-prediction of future NSSI, emotion dysregulation, and therapy
      status. These findings are consistent with the notion that instinctive barriers
      (e.g., aversion to NSSI stimuli, pain) dissuade most people from engaging in
      NSSI, and that the erosion of these barriers may facilitate NSSI.

PMID- 24886019
TI  - Clinical implications of SPRR1A expression in diffuse large B-cell lymphomas: a
      prospective, observational study.
AB  - BACKGROUND: Certain markers have been identified over the last 10 years that
      facilitate the prediction of a patient's prognosis; these markers have been
      proposed to be useful for risk stratification of lymphoma patients and for the
      development of specific therapeutic strategies. In the present study, we assessed
      the potential prognostic value of SPRR1A expression in 967 patients with diffuse
      large B-cell lymphomas. METHODS: All patients were enrolled between 2001 and 2007
      (median follow-up, 53.3 months) in the Second Hospital of Dalian Medical
      University, First Hospital of China Medical University, and Liaoning Cancer
      Hospital. Immunohistochemical analysis was used to evaluate the expression of
      SPRR1A. Survival was analyzed using the Kaplan-Meier method. Multivariate
      analysis was conducted to adjust the effect of SPRR1A expression for potential,
      well-known, independent prognostic factors. RESULTS: Of the 967 patients
      examined, SPRR1A expression was detected in 305 (31.54%) patients on
      immunohistochemical analysis. The 5-year survival rate was significantly lower in
      patients with SPRR1A expression than in those without (26.9% vs. 53.2%, P <
      0.001). Multivariate analysis identified SPRR1A expression as an independent
      predictor of survival in addition to lactate dehydrogenase level, clinical stage,
      and histologic subtype. CONCLUSIONS: SPRR1A expression may be useful as a
      prognostic factor for diffuse large B-cell lymphoma.

PMID- 24886020
TI  - The prognostic effect of perineural invasion in esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: Perineural invasion (PNI) is correlated with adverse survival in
      several malignancies, but its significance in esophageal squamous cell carcinoma
      (ESCC) remains to be clearly defined. The objective of this study was to
      determine the association between PNI status and clinical outcomes. METHODS: We
      retrospectively evaluated the PNI of 433 patients with ESCC treated with surgery
      between 2000 and 2007 at a single academic center. The resulting data were
      analyzed using Spearman's rank correlation, the Kaplan-Meier method, Cox
      proportional hazards regression modeling and Harrell's concordance index (C
      index). RESULTS: PNI was identified in 209 of the 433 (47.7%) cases of ESCC. The
      correlation analysis demonstrated that PNI in ESCC was significantly correlated
      with tumor differentiation, infiltration depth, pN classification and stage (P <
      0.05). The five-year overall survival rate was 0.570 for PNI-negative tumors
      versus 0.326 for PNI-positive tumors. Patients with PNI-negative tumors exhibited
      a 1.7-fold increase in five-year recurrence-free survival compared with patients
      with PNI-positive tumors (0.531 v 0.305, respectively; P < 0.0001). In the subset
      of patients with node-negative disease, PNI was evaluated as a prognostic
      predictor as well (P < 0.05). In the multivariate analysis, PNI was an
      independent prognostic factor for overall survival (P = 0.027). The C-index
      estimate for the combined model (PNI, gender and pN status) was a significant
      improvement on the C-index estimate of the clinicopathologic model alone (0.739 v
      0.706, respectively). CONCLUSIONS: PNI can function as an independent prognostic
      factor of outcomes in ESCC patients, and the PNI status in primary ESCC specimens
      should be considered for therapy stratification.

PMID- 24886021
TI  - Lesions of the nucleus accumbens core modulate development of matching behavior.
AB  - BACKGROUND: The development of choice is a crucial determinant in the performance
      of appetitive responses. Given two options with different reinforcement rates,
      animals match their relative rate of responding to the relative rates of
      reinforcement (i.e., matching behavior). A previous study has shown that the
      nucleus accumbens core (AcbC) is involved in the performance of matching behavior
      in trained animals. However, the role of the AcbC in the acquisition of matching
      behavior has not been addressed. RESULTS: We conducted a series of experimental
      sessions to examine the role of the AcbC on the development of matching behavior.
      Instrumental responding was measured in rats with excitotoxic lesions of the
      AcbC. Rats were given two options that differed in the relative rate of
      reinforcement under concurrent variable-interval schedules. The locations of the
      more frequently reinforced option and the alternative option were randomly
      switched between sessions. Lesions of the AcbC accelerated the development of
      matching behavior compared to the sham-operated group. The AcbC-lesioned rats
      exhibited closer conformity to the matching law than shams when the options were
      in the same positions as in the previous session (the same condition), but not
      when the option locations had been switched (the different condition). The AcbC
      rats showed smaller probabilities of switching behavior between alternatives than
      shams. Post-reinforcement pausing was not affected by the AcbC lesion. Neither
      numbers of rewards obtained nor number of lever presses were different between
      the AcbC-lesioned rats and shams over session blocks. CONCLUSIONS: Our results
      suggest that the AcbC plays a regulatory role in the development of matching
      behavior through switching probabilities rather than perception of reward
      magnitude. The differential effect of AcbC lesions on the matching behavior
      between the same and different conditions suggests influence of the spontaneous
      recovery, that is, reversion to a previously reinforced choice at the beginning
      of the next session, on the development of matching behavior in the AcbC-lesioned
      rats.

PMID- 24886022
TI  - Obesity epidemic has emerged among Nigerians.
AB  - BACKGROUND: Data from the WHO shows that the prevalence of overweight and obesity
      increased by ~20% between 2002 and 2010 in Nigeria. We conducted this study to
      examine the correlates of this fast growing epidemic. METHODS: We conducted a
      cross-sectional study among a random sample of 1058 adults, who were visitors and
      staff of a government worksite in Abuja, an urban city in Nigeria. The study
      participants had varying socio-economic status and a wide range of occupations,
      including skilled labor and professionals. Log-binomial regression models were
      used to estimate the multivariable-adjusted associations of potential
      determinants with the prevalence of overweight and obesity. RESULT: The mean age
      and body-mass index of the study population were 42 years +/- (9.3) and 27 kg/m2
      +/- (4.8). The overall prevalence of overweight or obesity (body-mass index >= 25
      kg/m2) was 64% (74% of the women and 57% of the men). For women compared to men,
      the prevalence ratio (PR) and (95% confidence interval, CI) was 1.24 (95% CI
      1.08, 1.43, p = 0.004), for overweight, and 2.54 (95% CI 2.08, 3.10, p =
      <0.0001), for obesity. Individuals aged 40 - 49 years were more likely to be
      overweight or obese. The PR for overweight and obesity was 1.45 (95% CI 1.07,
      1.97), p for age trend = 0.002 and 8.07(95% CI 3.01, 21.66, p for age trend =
      <0.0001) for those aged 40 - 49 years, compared with those aged <30 years.
      Compared with the individuals in the lower socio-economic status, the PR for
      obesity among those in the middle and high socio-economic statuses, were 1.39
      (95% CI 1.13, 1.72) and 1.24 (95% CI 0.97, 1.59) respectively, p for trend =
      0.003. CONCLUSION: About two-thirds of urban, professional, high socio-economic
      status Nigerian adults are either overweight or obese. The prevalence of
      overweight and obesity among this population of adult Nigerians, is as high as it
      is in the United Kingdom. Female gender and older age were independent predictors
      of overweight and obesity; while middle or high socio-economic status were
      independently associated with obesity.

PMID- 24886024
TI  - Health-related quality of life and influencing factors among rural left-behind
      wives in Liuyang, China.
AB  - BACKGROUND: In China, the number of left-behind wives in rural areas has reached
      47 million. Left-behind wives might have more psychological stress and lower life
      quality. This study was to examine the health-related quality of life and
      influencing social and cognitive factors in a sample of left-behind wives in
      rural areas of China. METHODS: The demographic data questionnaire, the Short Form
      36 Health Survey Scale, Center for Epidemiological Studies Depression Scale,
      Perceived Social Support Scale, Simplified Coping Style Questionnaire, and
      Perceived Stress Scale were completed by a sample of 1,893 left-behind wives and
      969 non-left-behind wives. RESULTS: Left-behind wives had lower scores on
      physical component summary (PCS), mental component summary (MCS) , and all the
      eight subscales of the SF-36 than non-left-behind wives (P < 0.05), especially on
      the role limitations due to emotional problems (RE) and on MCS. Compared to non
      left-behind wives, left-behind wives scored higher in depression, stress, and
      passive coping styles, and scored significantly lower in social support and
      active coping styles. Logistic regression analysis showed that the status of
      being left behind, age, education years, monthly income, employment, physical
      health status, active coping styles, and depression were influencing factors on
      the PCS of rural women, whereas the status of being left behind, monthly income,
      physical health status, sense of marriage security, stress, social support,
      passive coping styles, and depression were influencing factors on the MCS of
      rural women. CONCLUSIONS: Left-behind wives scored lower on health-related
      quality of life than non-left-behind wives. Low health-related quality of life
      was associated with left behind status, older age, less education, low monthly
      income, unemployment, bad physical health status, passive coping styles, low
      social support, high level of stress, and high depression.

PMID- 24886023
TI  - Infection with dengue-2 virus alters proteins in naturally expectorated saliva of
      Aedes aegypti mosquitoes.
AB  - BACKGROUND: Dengue virus (DENV) is responsible for up to approximately 300
      million infections and an increasing number of deaths related to severe
      manifestations each year in affected countries throughout the tropics. It is
      critical to understand the drivers of this emergence, including the role of
      vector-virus interactions. When a DENV-infected Aedes aegypti mosquito bites a
      vertebrate, the virus is deposited along with a complex mixture of salivary
      proteins. However, the influence of a DENV infection upon the expectorated
      salivary proteome of its vector has yet to be determined. METHODS: Therefore, we
      conducted a proteomic analysis using 2-D gel electrophoresis coupled with mass
      spectrometry based protein identification comparing the naturally expectorated
      saliva of Aedes aegypti infected with DENV-2 relative to that of uninfected Aedes
      aegypti. RESULTS: Several proteins were found to be differentially expressed in
      the saliva of DENV-2 infected mosquitoes, in particular proteins with anti
      hemostatic and pain inhibitory functions were significantly reduced. Hypothetical
      consequences of these particular protein reductions include increased biting
      rates and transmission success, and lead to alteration of transmission potential
      as calculated in our vectorial capacity model. CONCLUSIONS: We present our
      characterizations of these changes with regards to viral transmission and
      mosquito blood-feeding success. Further, we conclude that our proteomic analysis
      of Aedes aegypti saliva altered by DENV infection provides a unique opportunity
      to identify pro-viral impacts key to virus transmission.

PMID- 24886025
TI  - Radiographic signs for detection of femoroacetabular impingement and hip
      dysplasia should be carefully used in patients with osteoarthritis of the hip.
AB  - BACKGROUND: During the last years, terms like acetabular retroversion, excessive
      overcoverage, and abnormal head-neck-junction with the so called "pistol-grip
      deformity" has been added to the classical description of hip dysplasia. These
      anatomical changes could lead to a femoroacetabular impingement (FAI). Both kinds
      of FAI has been indentified as a main reason for hip pain and progressive
      degenerative changes leading to early osteoarthritis of the hip. A lot of
      radiographic criteria on pelvic views have been established to detect classical
      dysplasia and FAI. The present study was initiated to assess the hypothesis that
      age and severity of osteoarthritis affect measurements of different radiographic
      parameters. METHODS: The pelvic radiographs of 1614 patients were measured for
      head-ratio, CE-angle, roof obliquity, extrusion-index, depth-to-width ratio, CCD
      angle, sharp's angle. To evaluate the severity of osteoarthritis of the hip the
      classification by Kellgren and Lawrence was used. Associations between age and
      radiographic parameters or severity of osteoarthritis were assessed by Spearman's
      (rho) or Kendall's (r) rank correlation coefficient, respectively. RESULTS: 366
      (22.7%) patients presented no sign of osteoarthritis, 367 (22.7%) patients
      presented I degrees  osteoarthritis, 460 (28.5%) patients presented II degrees 
      osteoarthritis, 307 (19%) III degrees  osteoarthritis and 114 (7.1%) IV degrees 
      osteoarthritis of the hip. The mean head-ratio of all patients was 1.13 +/- 0.26
      (0.76 - 2.40), the mean CE-angle 40.05 degrees  +/- 10.13 degrees  (0 degrees  -
      70 degrees ), the mean roof obliquity was 35.27 degrees  +/- 4.96 degrees  (10
      degrees  - 55 degrees ), the mean extrusion-index was 12.99 +/- 9.21 (6.20 -
      95.2), the mean depth-to-width ratio was 59.30 +/- 8.90 (6.30 - 100), the mean
      CCD-angle was 127.68 degrees  +/- 7.22 degrees  (123 degrees  - 162 degrees ) and
      the mean sharp's angle was 9.75 degrees  +/- 5.40 degrees  (1 degrees  - 34
      degrees ) There was a weak association between age and the severity of
      osteoarthritis of the hips (left: r= 0.291; right: r=0.275; both P<0.001) with
      higher osteoarthritis levels observable for elderly patients). CONCLUSION:
      Severity of osteoarthritis has a negative impact on measurements of different
      radiographic parameters. Therefore - in our opinion - epidemiological studies on
      prearthrotic deformities should only be performed in healthy adults with no signs
      of osteoarthritic changes.

PMID- 24886026
TI  - National household survey of adverse childhood experiences and their relationship
      with resilience to health-harming behaviors in England.
AB  - BACKGROUND: Epidemiological and biomedical evidence link adverse childhood
      experiences (ACEs) with health-harming behaviors and the development of non
      communicable disease in adults. Investment in interventions to improve early life
      experiences requires empirical evidence on levels of childhood adversity and the
      proportion of HHBs potentially avoided should such adversity be addressed.
      METHODS: A nationally representative survey of English residents aged 18 to 69 (n
      = 3,885) was undertaken during the period April to July 2013. Individuals were
      categorized according to the number of ACEs experienced. Modeling identified the
      proportions of HHBs (early sexual initiation, unintended teenage pregnancy,
      smoking, binge drinking, drug use, violence victimization, violence perpetration,
      incarceration, poor diet, low levels of physical exercise) independently
      associated with ACEs at national population levels. RESULTS: Almost half (47%) of
      individuals experienced at least one of the nine ACEs. Prevalence of childhood
      sexual, physical, and verbal abuse was 6.3%, 14.8%, and 18.2% respectively
      (population-adjusted). After correcting for sociodemographics, ACE counts
      predicted all HHBs, e.g. (0 versus 4+ ACEs, adjusted odds ratios (95% confidence
      intervals)): smoking 3.29 (2.54 to 4.27); violence perpetration 7.71 (4.90 to
      12.14); unintended teenage pregnancy 5.86 (3.93 to 8.74). Modeling suggested that
      11.9% of binge drinking, 13.6% of poor diet, 22.7% of smoking, 52.0% of violence
      perpetration, 58.7% of heroin/crack cocaine use, and 37.6% of unintended teenage
      pregnancy prevalence nationally could be attributed to ACEs. CONCLUSIONS: Stable
      and protective childhoods are critical factors in the development of resilience
      to health-harming behaviors in England. Interventions to reduce ACEs are
      available and sustainable, with nurturing childhoods supporting the adoption of
      health-benefiting behaviors and ultimately the provision of positive childhood
      environments for future generations.

PMID- 24886027
TI  - Developmentally adapted cognitive processing therapy for adolescents and young
      adults with PTSD symptoms after physical and sexual abuse: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Although childhood sexual and/or physical abuse (CSA/CPA) is known to
      have severe psychopathological consequences, there is little evidence on
      psychotherapeutic interventions for adolescents and young adults suffering from
      post-traumatic stress disorder (PTSD). Equally sparse are data on moderators of
      treatment response on PTSD-related epigenetic changes, health care costs and loss
      of productivity, alterations in cognitive processing, and on how successful
      interventions affect all of these factors. Early treatment may prevent later
      (co)morbidity. In this paper, we present a study protocol for the evaluation of a
      newly developed psychotherapeutic manual for PTSD after CSA/CPA in adolescents
      and young adults - the Developmentally Adapted Cognitive Processing Therapy (D
      CPT). METHODS/DESIGN: In a multicenter randomized controlled trial (RCT) D-CPT is
      compared to treatment as usual (TAU). A sample of 90 adolescent outpatients aged
      14 to 21 years will be randomized to one of these conditions. Four assessments
      will be carried out at baseline, at end of treatment, and 3 and 6 months after
      end of therapy. Each time, patients will be assessed via clinical interviews and
      a wide range of questionnaires. In addition to PTSD symptoms and comorbidities,
      we will evaluate moderators of treatment response, epigenetic profiles, direct
      and indirect costs of this disorder, and neurophysiological processing of threat
      cues in PTSD and their respective changes in the course of these two treatments
      (D-CPT and TAU). DISCUSSION: The study will provide new insights in the
      understudied field of PTSD in adolescents and young adults. A newly developed
      intervention will be evaluated in this therapeutically underserved population.
      Results will provide data on treatment efficacy, direct and indirect treatment
      costs, as well as on associations of treatment outcome and PTSD intensity both to
      epigenetic profiles and to the neurobiological processing of threat cues.
      Besides, they will help to learn more about the psychopathology and possible new
      objective correlates of PTSD. TRIAL REGISTRATION: Germanctr.de identifier:
      DRKS00004787.

PMID- 24886028
TI  - Epidemic and virulence characteristic of Shigella spp. with extended-spectrum
      cephalosporin resistance in Xiaoshan District, Hangzhou, China.
AB  - BACKGROUND: Shigellae have become increasingly resistant to the extended-spectrum
      cephalosporin (ESC) worldwide and pose a great challenge to anti-infection
      treatment options. The purpose of this study was to determine the resistance,
      cephalosporin resistance mechanisms, virulence characteristic and genotype of ESC
      resistant Shigella. METHODS: From 2008 to 2012, Shigella isolates collected from
      diarrhea patients were detected for antibiotics sensitivity by disk diffusion,
      cephalosporin resistance determinants and virulence genes using polymerase chain
      reaction (PCR) and genotyping through enterobacterial repetitive intergenic
      consensus sequence PCR (ERIC-PCR). RESULTS: A total of 356 Shigella isolates were
      gathered, and 198 (55.6%, 58 S. flexneri and 140 S. sonnei) were resistant to
      ESC. All ESC-resistant isolates were susceptible to imipenem, and only 0.5%
      isolate was resistant to piperacillin/tazobactam. ESC-resistant S. flexneri
      showed high degrees of resistance to ampicillin (100%), ampicillin/sulbactam
      (96.6%), piperacillin (100%), trimethoprim/sulfamethoxazole (74.1%),
      ciprofloxacin (74.1%), levofloxacin (53.4%), ceftazidime (58.6%) and cefepime
      (58.6%). ESC-resistant S. sonnei exhibited high resistance rates to ampicillin
      (100%), piperacillin (100%) and trimethoprim/sulfamethoxazole (96.4%).
      Cephalosporin resistance genes were confirmed in 184 ESC-resistant isolates.
      bla(CTX-M) types (91.8%, mainly bla(CTX-M-14), bla(CTX-M-15) and bla(CTX-M-57))
      were most prevalent, followed by bla(OXA-30) (26.3%). Over 99.0% ESC-resistant
      isolates harbored virulence genes ial, ipaH, virA and sen. However, set1 were
      more prevalent in ESC-resistant S. flexneri isolates than in S. sonnei isolates.
      ERIC-PCR results showed that 2 and 3 main genotypes were detected in ESC
      resistant S. flexneri and S. sonnei, respectively. CONCLUSION: Our findings
      indicated that a high prevalence of ESC-resistant Shigella mediated mainly by
      bla(CTX-M) with stronger resistance and virulence, and the existence of specific
      clones responsible for these Shigella infection in the region studied.

PMID- 24886029
TI  - Patient factors to target for elimination of mother-to-child transmission of HIV.
AB  - BACKGROUND: There is great impetus to achieve elimination of mother-to-child
      transmission of HIV (eMTCT) by 2015, and part of this is to identify factors to
      target to achieve the goal. This study thus identified key patient factors for
      MTCT in a high HIV prevalence setting in Johannesburg, South Africa. Between
      November 2010 and May 2012, we conducted a case-control study among HIV-infected
      women with HIV-infected (cases) and uninfected (controls) infants diagnosed
      around six weeks of age as part of routine, early infant diagnosis. Mothers and
      infants were identified through registers in six healthcare facilities that
      provide antenatal, postpartum and HIV care. Structured interviews were conducted
      with a focus on history of HIV infection, antenatal, intrapartum and immediate
      postpartum management of the mother-infant pair. Patient-related risk factors for
      MTCT were identified. RESULTS: A total of 77 women with HIV-infected infants and
      154 with -uninfected infants were interviewed. Among HIV-infected cases, 13.0% of
      the women knew their HIV status prior to conception, and 83.1% reported their
      pregnancies as unplanned. Antenatal antiretroviral coverage was high in the
      control group - only 1/154 (0.7%) reported receiving no prophylaxis or treatment
      compared with 17/74 (22.9%) of cases. In multivariate analysis, key patient
      related risks for HIV transmission were: unknown HIV status prior to conception
      (adjusted odds ratio [AOR] = 6.6; 95% CI = 2.4 - 18.4; p < 0.001); accessing
      antenatal care after 20 weeks gestation (AOR = 4.3; 95% CI = 2.0 - 9.3; p <
      0.001); less than 12 years of formal education (AOR = 3.4; 95% CI = 1.6 - 7.5; p
      = 0.002); and unplanned pregnancy (AOR = 2.7; 95% CI = 1.2 to 6.3; p = 0.022).
      Mean age at first HIV test was 6.6 weeks (SD = 3.5) for infants who were
      diagnosed as HIV-infected, and the mean age at antiretroviral treatment
      initiation was 10.8 weeks (SD = 4.4). HIV-uninfected infants were diagnosed at a
      mean age of 6.0 weeks (SD = 0.2). CONCLUSIONS: Undiagnosed maternal HIV infection
      prior to conception, unplanned pregnancies, delays in accessing antenatal care,
      and low levels of education were the most significant patient risk factors
      associated with MTCT. While the emphasis has been on increasing availability and
      coverage of efficacious antiretroviral regimens, and strengthening health systems
      within eMTCT initiatives, there is a need to also address patient-related factors
      if we are to achieve eMTCT goals.

PMID- 24886030
TI  - Illustrated operative management of spontaneous bleeding and compartment syndrome
      of the lower extremity in a patient with acquired hemophilia A: a case report.
AB  - INTRODUCTION: Spontaneous bleeding resulting in compartment syndrome at the lower
      adult leg due to acquired hemophilia A is rare. There are no reports on operative
      management of this entity. CASE PRESENTATION: We present a case of atraumatic
      compartment syndrome of the lower leg due to acquired factor VIII deficiency, in
      an 83-year-old Caucasian man of European descent. He was treated surgically with
      a long and complicated postoperative course after presenting to a community
      hospital with a 2-day history of increasing pain and swelling in his left lower
      leg without a previous history of trauma. CONCLUSIONS: Awareness, prompt
      diagnosis and effective treatment of compartment syndrome caused by a rare
      bleeding disorder, which is usually acquired by the elderly, is essential and may
      spare a patient from surgery or even limb loss, if early administration of
      recombinant factor VIIa is effective. The course of disease in a patient with
      operative management of spontaneous bleeding, compartment syndrome and acquired
      hemophilia A may be prolonged. However, an interdisciplinary approach with
      meticulous surgical treatment and bleeding management with recombinant factor
      VIIa as well as inhibitor eradication by immunosuppressive treatment can be
      successful and expensive.

PMID- 24886031
TI  - Automatic pulmonary fissure detection and lobe segmentation in CT chest images.
AB  - BACKGROUND: Multi-detector Computed Tomography has become an invaluable tool for
      the diagnosis of chronic respiratory diseases. Based on CT images, the automatic
      algorithm to detect the fissures and divide the lung into five lobes will help
      regionally quantify, amongst others, the lung density, texture, airway and, blood
      vessel structures, ventilation and perfusion. METHODS: Sagittal adaptive fissure
      scanning based on the sparseness of the vessels and bronchi is employed to
      localize the potential fissure region. Following a Hessian matrix based line
      enhancement filter in the coronal slice, the shortest path is determined by means
      of Uniform Cost Search. Implicit surface fitting based on Radial Basis Functions
      is used to extract the fissure surface for lobe segmentation. By three implicit
      fissure surface functions, the lung is divided into five lobes. The proposed
      algorithm is tested by 14 datasets. The accuracy is evaluated by the mean (+/
      S.D.), root mean square, and the maximum of the shortest Euclidian distance from
      the manually-defined fissure surface to that extracted by the algorithm. RESULTS:
      Averaged over all datasets, the mean (+/-S.D.), root mean square, and the maximum
      of the shortest Euclidian distance are 2.05 +/- 1.80, 2.46 and 7.34 mm for the
      right oblique fissure. The measures are 2.77 +/- 2.12, 3.13 and 7.75 mm for the
      right horizontal fissure, 2.31 +/- 1.76, 3.25 and 6.83 mm for the left oblique
      fissure. The fissure detection works for the data with a small lung nodule nearby
      the fissure and a small lung subpleural nodule. The volume and emphysema index of
      each lobe can be calculated. The algorithm is very fast, e.g., to finish the
      fissure detection and fissure extension for the dataset with 320 slices only
      takes around 50 seconds. CONCLUSIONS: The sagittal adaptive fissure scanning can
      localize the potential fissure regions quickly. After the potential region is
      enhanced by a Hessian based line enhancement filter, Uniform Cost Search can
      extract the fissures successfully in 2D. Surface fitting is able to obtain three
      implicit surface functions for each dataset. The current algorithm shows good
      accuracy, robustness and speed, may help locate the lesions into each lobe and
      analyze them regionally.

PMID- 24886032
TI  - Efficacy of adalimumab in young children with juvenile idiopathic arthritis and
      chronic uveitis: a case series.
AB  - BACKGROUND: Juvenile idiopathic arthritis is a relatively common chronic disease
      of childhood, and is associated with persistent morbidity and extra-articular
      complications, one of the most common being uveitis. The introduction of biologic
      therapies, particularly those blocking the inflammatory mediator tumor necrosis
      factor-alpha, provided a new treatment option for juvenile idiopathic arthritis
      patients who were refractory to standard therapy such as non-steroidal anti
      inflammatory drugs, corticosteroids and/or methotrexate. CASE PRESENTATIONS: The
      first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis
      who failed to respond to treatment with anti-inflammatories, low-dose
      corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2
      every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy;
      steroid tapering and withdrawal started after 1 month. After 2 months the patient
      showed good control of articular and ocular manifestations, and she remained in
      remission for 1 year, receiving adalimumab and methotrexate with no side effects,
      and showing significant improvement in growth. Case 2 was a 9-year-old boy with
      an 8-year history of juvenile idiopathic arthritis and uveitis that initially
      responded to infliximab, but relapse occurred after 2 years off therapy. After
      switching to adalimumab, and adjusting doses of both adalimumab and methotrexate
      based on body surface area, the patient showed good response and corticosteroids
      were tapered and withdrawn after 6 months; the patient remained in remission
      taking adalimumab and methotrexate. The final case was a 5-year-old girl with
      juvenile idiopathic arthritis for whom adalimumab was added to methotrexate
      therapy after three flares of uveitis. The patient had two subsequent episodes of
      uveitis that responded well to local therapy, but was then free of both juvenile
      idiopathic arthritis and uveitis symptoms, allowing methotrexate and then
      adalimumab to be stopped; the patient remained in drug-free remission.
      CONCLUSION: This report includes the first published case of the use of
      adalimumab in a child aged <3 years. Our clinical experience further supports the
      use of biologic therapy for the management of juvenile idiopathic arthritis and
      uveitis in children as young as two years of age.

PMID- 24886034
TI  - The Memory Aid study: protocol for a randomized controlled clinical trial
      evaluating the effect of computer-based working memory training in elderly
      patients with mild cognitive impairment (MCI).
AB  - BACKGROUND: Mild cognitive impairment (MCI) is a condition characterized by
      memory problems that are more severe than the normal cognitive changes due to
      aging, but less severe than dementia. Reduced working memory (WM) is regarded as
      one of the core symptoms of an MCI condition. Recent studies have indicated that
      WM can be improved through computer-based training. The objective of this study
      is to evaluate if WM training is effective in improving cognitive function in
      elderly patients with MCI, and if cognitive training induces structural changes
      in the white and gray matter of the brain, as assessed by structural MRI.
      METHODS/DESIGNS: The proposed study is a blinded, randomized, controlled trail
      that will include 90 elderly patients diagnosed with MCI at a hospital-based
      memory clinic. The participants will be randomized to either a training program
      or a placebo version of the program. The intervention is computerized WM training
      performed for 45 minutes of 25 sessions over 5 weeks. The placebo version is
      identical in duration but is non-adaptive in the difficulty level of the tasks.
      Neuropsychological assessment and structural MRI will be performed before and 1
      month after training, and at a 5-month folllow-up. DISCUSSION: If computer-based
      training results in positive changes to memory functions in patients with MCI
      this may represent a new, cost-effective treatment for MCI. Secondly, evaluation
      of any training-induced structural changes to gray or white matter will improve
      the current understanding of the mechanisms behind effective cognitive
      interventions in patients with MCI. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01991405. November 18, 2013.

PMID- 24886033
TI  - Secretome analysis reveals effector candidates associated with broad host range
      necrotrophy in the fungal plant pathogen Sclerotinia sclerotiorum.
AB  - BACKGROUND: The white mold fungus Sclerotinia sclerotiorum is a devastating
      necrotrophic plant pathogen with a remarkably broad host range. The interaction
      of necrotrophs with their hosts is more complex than initially thought, and still
      poorly understood. RESULTS: We combined bioinformatics approaches to determine
      the repertoire of S. sclerotiorum effector candidates and conducted detailed
      sequence and expression analyses on selected candidates. We identified 486 S.
      sclerotiorum secreted protein genes expressed in planta, many of which have no
      predicted enzymatic activity and may be involved in the interaction between the
      fungus and its hosts. We focused on those showing (i) protein domains and motifs
      found in known fungal effectors, (ii) signatures of positive selection, (iii)
      recent gene duplication, or (iv) being S. sclerotiorum-specific. We identified 78
      effector candidates based on these properties. We analyzed the expression pattern
      of 16 representative effector candidate genes on four host plants and revealed
      diverse expression patterns. CONCLUSIONS: These results reveal diverse predicted
      functions and expression patterns in the repertoire of S. sclerotiorum effector
      candidates. They will facilitate the functional analysis of fungal pathogenicity
      determinants and should prove useful in the search for plant quantitative disease
      resistance components active against the white mold.

PMID- 24886035
TI  - Deregulation of inflammatory response in the diabetic condition is associated
      with increased ischemic brain injury.
AB  - BACKGROUND: Although elicited inflammation contributes to tissue injury, a
      certain level of inflammation is necessary for subsequent tissue
      repair/remodeling. Diabetes, a chronic low-grade inflammatory state, is a
      predisposing risk factor for stroke. The condition is associated with delayed
      wound healing, presumably due to disrupted inflammatory responses. With inclusion
      of the diabetic condition in an experimental animal model of stroke, this study
      investigates whether the condition alters inflammatory response and influences
      stroke-induced brain injury. METHODS: C57BL/6 mice were fed a diabetic diet (DD)
      for 8 weeks to induce an experimental diabetic condition or a normal diet (ND)
      for the same duration. Gene expression of inflammatory factors including monocyte
      chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), CCR2, and CD36 was
      assessed in the peripheral immune cells and brains of normal and diabetic mice
      before and after focal cerebral ischemia. The expression of these factors was
      also determined in lipopolysaccharide (LPS)-treated cultured normal and diabetic
      macrophages. Ischemic outcome was assessed in these mice at 3 days post-ischemia.
      RESULTS: DD intervention in mice resulted in obesity and elevated insulin and
      glucose level in the blood. The peritoneal immune cells from the diabetic mice
      showed higher MCP-1 mRNA levels before and after stroke. Compared to normal mice,
      diabetic mice showed reduced MCP-1, IL-6, and CCR2 gene expression in the brain
      at 6 h post-ischemia. LPS-stimulated inflammatory responses were also reduced in
      the diabetic macrophages. The diabetic mice showed larger infarct size and
      percent swelling. CONCLUSIONS: These results showed that diabetic conditions
      deregulate acute inflammatory response and that the condition is associated with
      increased stroke-induced injury. The study suggests that interventions aimed at
      restoring appropriate inflammatory response in peripheral immune
      cells/macrophages may be beneficial in reducing stroke-induced brain injury in
      subjects with chronic inflammatory conditions.

PMID- 24886036
TI  - Double-blind controlled trial of lecithinized superoxide dismutase in patients
      with idiopathic interstitial pneumonia - short term evaluation of safety and
      tolerability.
AB  - BACKGROUND: Idiopathic interstitial pneumonias such as idiopathic pulmonary
      fibrosis or fibrotic nonspecific interstitial pneumonia are irreversible
      progressive pulmonary diseases that often have fatal outcomes. Although the
      etiology of idiopathic interstitial pneumonias is not yet fully understood, anti
      fibrotic and anti-inflammatory agents have shown limited therapeutic
      effectiveness. Reactive oxygen species and their cytotoxic effects on the lung
      epithelial cells have been reported to participate in the pathophysiology of the
      disease. Because superoxide dismutase catalyzes the detoxification of reactive
      oxygen species, we developed lecithinized superoxide dismutase for the treatment
      of patients with idiopathic interstitial pneumonias. METHODS: A multicenter,
      randomized, placebo-controlled trial was conducted as a pilot study to
      investigate the safety and effectiveness of 40 or 80 mg lecithinized superoxide
      dismutase in patients with progressive idiopathic interstitial pneumonias who
      presented with either idiopathic pulmonary fibrosis or corticosteroid-resistant
      fibrotic nonspecific interstitial pneumonia and showed arterial oxygen tension
      compatible with stage III or IV on the Japanese severity grading scale for
      idiopathic interstitial pneumonias. Before and following infusion of lecithinized
      superoxide dismutase for 28 days, the primary endpoint of forced vital capacity
      and the secondary endpoints of lactate dehydrogenase, surfactant protein-A,
      surfactant protein-D and Krebs von den Lungen-6 levels were measured in the
      serum. RESULTS: The primary endpoint of forced vital capacity did not improve
      significantly in the lecithinized superoxide dismutase groups in comparison with
      the placebo group. The secondary endpoints of lactate dehydrogenase and
      surfactant protein-A levels were significantly attenuated by 28 days in the
      higher-dose (80 mg) group. However, these changes returned to the baseline levels
      by 56 days after the cessation of lecithinized superoxide dismutase. Adverse
      events and mortality in the drug-treated groups did not differ from those in the
      placebo group. CONCLUSIONS: Treatment with lecithinized superoxide dismutase is
      safe and improves the levels of serum markers such as lactate dehydrogenase and
      surfactant protein-A in patients with advanced idiopathic interstitial pneumonias
      with severe respiratory dysfunction. Considering the results of the current
      study, further investigations into the effects and treatment potential of long
      term administration of lecithinized superoxide dismutase may be warranted. TRIAL
      REGISTRATION: University hospital Medical Information Network (UMIN) clinical
      trials registry no. 000000752.

PMID- 24886037
TI  - Reproducibility of and sex differences in common orthopaedic ankle and foot tests
      in runners.
AB  - BACKGROUND: For future etiologic cohort studies in runners it is important to
      identify whether (hyper)pronation of the foot, decreased ankle joint dorsiflexion
      (AJD) and the degree of the extension of the first Metatarsophalangeal joint
      (MTP1) are risk factors for running injuries and to determine possible sex
      differences.These parameters are frequently determined with the navicular drop
      test (NDT) Stance and Single Limb-Stance, the Ankle Joint Dorsiflexion-test, and
      the extension MTP1-test in a healthy population. The aim of this clinimetric
      study was to determine the reproducibility of these three orthopaedic tests in
      runners, using minimal equipment in order to make them applicable in large cohort
      studies. Furthermore, we aimed to determine possible sex differences of these
      tests. METHODS: The three orthopaedic tests were administered by two sports
      physiotherapists in a group of 42 (22 male and 20 female) recreational runners.
      The intra-class correlation (ICC) for interrater and intrarater reliability and
      the standard error of measurement (SEM) were calculated. Bland and Altman plots
      were used to determine the 95% limits of agreements (LOAs). Furthermore, the
      difference between female and male runners was determined. RESULTS: The ICC's of
      the NDT were in the range of 0.37 to 0.45, with a SEM in the range of 2.5 to 5
      mm. The AJD-test had an ICC of 0.88 and 0.86 (SEM 2.4 degrees  and 8.7 degrees ),
      with a 95% LOA of -6.0 degrees  to 6.3 degrees  and -5.3 degrees  to 7.9 degrees
      , and the MTP1-test had an ICC of 0.42 and 0.62 (SEM 34.4 degrees  and 9.9
      degrees ), with a 95% LOA of -30.9 degrees  to 20.7 degrees  and -20 degrees  to
      17.8 degrees  for the interrater and intrarater reproducibility,
      respectively.Females had a significantly (p<0.05) lower navicular drop score and
      higher range of motion in extension of the MTP1, but no sex differences were
      found for ankle dorsiflexion (p >= 0.05). CONCLUSION: The reproducibility for the
      AJD test in runners is good, whereas that of the NDT and extension MTP1 was
      moderate or low. We found a difference in NDT and MTP1 mobility between female
      and male runners, however this needs to be established in a larger study with
      more reliable test procedures.

PMID- 24886038
TI  - Agreement between cranial and facial classification through clinical observation
      and anthropometric measurement among Envigado school children.
AB  - BACKGROUND: To evaluate the agreement between cranial and facial classification
      obtained by clinical observation and anthropometric measurements among school
      children from the municipality of Envigado, Colombia. METHODS: This cross
      sectional study was carried out among 8-15-year-old children. Initially, an
      indirect clinical observation was made to determine the skull pattern
      (dolichocephalic, mesocephalic or brachycephalic), based on visual equivalence of
      right eurion- left eurion and glabella-opisthocranion anthropometric points, as
      well as the facial type (leptoprosopic, mesoprosopic and euryprosopic), according
      to the left and right zygomatic, nasion and gnation points. Following, a direct
      measurement was conducted with an anthropometer using the same landmarks for
      cranial width and length, as well as for facial width and height. Subsequently,
      both the facial index [euryprosopic (<=80.9%), mesoprosopic (between 81% - 93%)
      and leptoprosopic (>=93.1%)] and the cranial index [dolichocephalic (index <=
      75.9%), mesocephalic (between 76% - 81%), and brachycephalic (>=81.1%)] were
      determined. Concordance between the indices obtained was calculated by direct and
      indirect measurement using the Kappa statistic. RESULTS: A total of 313 students
      were enrolled; 172 (55%) were female and 141 (45%) male. The agreement between
      the direct and indirect facial index measurements was 0.189 (95% CI 0.117-0261),
      and the cranial index was 0.388 (95% CI 0.304-0.473), indicating poor
      concordance. CONCLUSIONS: No agreement was observed between direct measurements
      conducted with an anthropometer and indirect measurements via visual evaluation.
      Therefore, the indirect visual classification method is not appropriate to
      calculate the cranial and facial indices.

PMID- 24886039
TI  - Real-time PCR assays for genotyping of Cryptococcus gattii in North America.
AB  - BACKGROUND: Cryptococcus gattii has been the cause of an ongoing outbreak
      starting in 1999 on Vancouver Island, British Columbia and spreading to mainland
      Canada and the US Pacific Northwest. In the course of the outbreak, C. gattii has
      been identified outside of its previously documented climate, habitat, and host
      disease. Genotyping of C. gattii is essential to understand the ecological and
      geographical expansion of this emerging pathogen. METHODS: We developed and
      validated a mismatch amplification mutation assay (MAMA) real-time PCR panel for
      genotyping C. gattii molecular types VGI-VGIV and VGII subtypes a,b,c. Subtype
      assays were designed based on whole-genome sequence of 20 C. gattii strains.
      Publically available multilocus sequence typing (MLST) data from a study of 202
      strains was used for the molecular type (VGI-VGIV) assay design. All assays were
      validated across DNA from 112 strains of diverse international origin and sample
      types, including animal, environmental and human. RESULTS: Validation revealed
      each assay on the panel is 100% sensitive, specific and concordant with MLST. The
      assay panel can detect down to 0.5 picograms of template DNA. CONCLUSIONS: The
      (MAMA) real-time PCR panel for C. gattii accurately typed a collection of 112
      diverse strains and demonstrated high sensitivity. This is a time and cost
      efficient method of genotyping C. gattii best suited for application in large
      scale epidemiological studies.

PMID- 24886040
TI  - Successful treatment of a ruptured aneurysm at the vertebral artery-posterior
      inferior cerebellar artery junction and simultaneous treatment of the stenotic
      vertebral artery with a single flow-diverting stent: a case report.
AB  - INTRODUCTION: This is the first report on the simultaneous successful treatment
      of a large ruptured saccular aneurysm and stenotic parent artery with a single
      flow-diverting stent. CASE PRESENTATION: We report the case of a 68-year-old
      Caucasian man with occlusion of the right vertebral artery and a ruptured
      aneurysm at the junction of the left posterior inferior cerebellar artery-left
      vertebral artery that was successfully treated by the deployment of a single flow
      diverting stent in the stenotic left vertebral artery. Stent deployment was
      complicated by thrombotic occlusion of the basilar artery, which was successfully
      reopened. The patient recovered completely, and follow-up angiography at 4 months
      and 1 year showed patent vertebral artery with gradual shrinkage of the aneurysm.
      CONCLUSIONS: This report contributes to the literature on treatment of large
      ruptured aneurysms localized in stenotic arteries and in areas of the endocranium
      where a mass of embolic material in the aneurysm (coils) might compromise the
      circulation in the parent blood vessel or compress vital brain structures.

PMID- 24886042
TI  - Effects of long-term low-level radiation exposure after the Chernobyl catastrophe
      on immunoglobulins in children residing in contaminated areas: prospective and
      cross-sectional studies.
AB  - BACKGROUND: After the Chernobyl nuclear incident in 1986, children in the
      Narodichesky region, located 80 km west of the Chernobyl Power Plant, were
      exposed to 137Cesium (137Cs). Little is known about the effects of chronic low
      level radiation on humoral immune responses in children residing in contaminated
      areas. METHODS: In four different approaches we investigated the effect of
      residential 137Cs exposure on immunoglobulins A, G, M, and specific
      immunoglobulin E in children. In a dynamic cohort (1993-1998) we included 617
      children providing 2,407 repeated measurements; 421 and 523 children in two cross
      sectional samples (1997-1998 and 2008-2010, respectively); and 25 participants in
      a small longitudinal cohort (1997-2010). All medical exams, blood collections,
      and analyses were conducted by the same team. We used mixed linear models to
      analyze repeated measurements in cohorts and general linear regression models for
      cross-sectional studies. RESULTS: Residential soil contamination in 2008 was
      highly correlated with the individual body burden of 137Cs. Serum IgG and IgM
      concentrations increased between 1993 and 1998. Children with higher 137Cs soil
      exposure had lower serum IgG levels, which, however, increased in the small
      cohort assessed between 1997 and 2010. Children within the fourth quintile of
      137Cs soil exposure (266-310 kBq/m2) had higher IgM serum concentrations between
      1993 and 1998 but these declined between 1997 and 2010. IgA remained stable with
      median 137Cs exposures related to higher IgA levels, which was corroborated in
      the cross-sectional study of 2008-2010. Specific IgE against indoor allergens was
      detected less often in children with higher 137Cs exposure. CONCLUSIONS: Our
      findings show radiation-related alterations of immunoglobulins which by
      themselves do not constitute adverse health effects. Further investigations are
      necessary to understand how these changes affect health status.

PMID- 24886041
TI  - Genomic analysis of the emergence of 20th century epidemic dysentery.
AB  - BACKGROUND: Shigella dysenteriae type 1 (Sd1) causes recurrent epidemics of
      dysentery associated with high mortality in many regions of the world. Sd1
      infects humans at very low infectious doses (10 CFU), and treatment is
      complicated by the rapid emergence of antibiotic resistant Sd1 strains. Sd1 is
      only detected in the context of human infections, and the circumstances under
      which epidemics emerge and regress remain unknown. RESULTS: Phylogenomic analyses
      of 56 isolates collected worldwide over the past 60 years indicate that the Sd1
      clone responsible for the recent pandemics emerged at the turn of the 20th
      century, and that the two world wars likely played a pivotal role for its
      dissemination. Several lineages remain ubiquitous and their phylogeny indicates
      several recent intercontinental transfers. Our comparative genomics analysis
      reveals that isolates responsible for separate outbreaks, though closely related
      to one another, have independently accumulated antibiotic resistance genes,
      suggesting that there is little or no selection to retain these genes in-between
      outbreaks. The genomes appear to be subjected to genetic drift that affects a
      number of functions currently used by diagnostic tools to identify Sd1, which
      could lead to the potential failure of such tools. CONCLUSIONS: Taken together,
      the Sd1 population structure and pattern of evolution suggest a recent emergence
      and a possible human carrier state that could play an important role in the
      epidemic pattern of infections of this human-specific pathogen. This analysis
      highlights the important role of whole-genome sequencing in studying pathogens
      for which epidemiological or laboratory investigations are particularly
      challenging.

PMID- 24886043
TI  - Comparison of intervention effects in split-mouth and parallel-arm randomized
      controlled trials: a meta-epidemiological study.
AB  - BACKGROUND: Split-mouth randomized controlled trials (RCTs) are popular in oral
      health research. Meta-analyses frequently include trials of both split-mouth and
      parallel-arm designs to derive combined intervention effects. However, carry-over
      effects may induce bias in split- mouth RCTs. We aimed to assess whether
      intervention effect estimates differ between split- mouth and parallel-arm RCTs
      investigating the same questions. METHODS: We performed a meta-epidemiological
      study. We systematically reviewed meta- analyses including both split-mouth and
      parallel-arm RCTs with binary or continuous outcomes published up to February
      2013. Two independent authors selected studies and extracted data. We used a two
      step approach to quantify the differences between split-mouth and parallel-arm
      RCTs: for each meta-analysis. First, we derived ratios of odds ratios (ROR) for
      dichotomous data and differences in standardized mean differences (?SMD) for
      continuous data; second, we pooled RORs or ?SMDs across meta-analyses by random
      effects meta-analysis models. RESULTS: We selected 18 systematic reviews, for 15
      meta-analyses with binary outcomes (28 split-mouth and 28 parallel-arm RCTs) and
      19 meta-analyses with continuous outcomes (45 split-mouth and 48 parallel-arm
      RCTs). [corrected]. Effect estimates did not differ between split-mouth and
      parallel-arm RCTs (mean ROR, 0.96, 95% confidence interval 0.52-1.80; mean ?SMD,
      0.08, -0.14-0.30). CONCLUSIONS: Our study did not provide sufficient evidence for
      a difference in intervention effect estimates derived from split-mouth and
      parallel-arm RCTs. Authors should consider including split-mouth RCTs in their
      meta-analyses with suitable and appropriate analysis.

PMID- 24886044
TI  - Palliative gastrostomy in the setting of voluminous ascites.
AB  - OBJECTIVE: We report the indications, methods, and complications of percutaneous
      gastrostomy/gastrojejunostomy (G/GJ) in patients with voluminous ascites.
      METHODS: Following institutional review board approval, 69 patients (14 male, 55
      female, mean age 58+/-12 years, range 32-89 years) who underwent percutaneous
      G/GJ with paracentesis were identified from a prospectively acquired database.
      Electronic medical record data extracted included diagnosis, method of G/GJ
      insertion, clinical course, and complications, which were graded by The Society
      of Interventional Radiology (SIR) criteria. Statistics were performed using
      Graphpad Instat. RESULTS: Sixty-six G and three GJ catheters were placed in 62
      patients with malignant and 7 patients with benign disease; 47 procedures were
      conducted using fluoroscopy and 22 using computed tomography (CT; 10 patients had
      failed fluoroscopy). Sixty-six patients had 1980+/-1371 mL (range, 20-5000 mL)
      ascites drained (more in males, p=0.01) 0.8+/-1.6 days (range, 0-5 days) prior to
      placement. Forty-one patients had significantly less ascites (1895+/-1426 mL;
      range, 100-5400 mL) drained after G/GJ (p>0.0.5). Mean survival after insertion
      was 43+/-57 days (range, 1-252 days) among 38 patients for whom data were
      available. Fifty-six patients had a mean postprocedure hospital stay of 8.6+/-8.4
      days (range, 0-45 days); 3 were outpatients and 10 patients died in the hospital.
      Successful gastropexy was confirmed on subsequent cross-sectional imaging in 22
      of 25 patients. There were 25 tube maintenance issues that included catheter
      displacement and leakage, one patient experienced hemorrhage, and there were two
      deaths. All except one patient had satisfactory gastrostomy function. CONCLUSION:
      Effective G/GJ placement is possible in most patients with voluminous ascites
      provided ascites is drained and gastrocutaneous fistula formation occurs. Caution
      is advised; placement is generally for fragile terminal patients, and fluoroscopy
      or CT guidance is required.

PMID- 24886045
TI  - Increase in hippocampal water diffusion and volume during experimental
      pneumococcal meningitis is aggravated by bacteremia.
AB  - BACKGROUND: The hippocampus undergoes apoptosis in experimental pneumococcal
      meningitis leading to neurofunctional deficits in learning and memory function.
      The aim of the present study was 1) to investigate hippocampal apparent diffusion
      coefficient (ADC) and volume with MRI during the course of experimental
      pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia
      on hippocampal water distribution and volume, 3) and to correlate these findings
      to the extent of apoptosis in the hippocampus. METHODS: Experimental meningitis
      in rats was induced by intracisternal injection of live pneumococci. The study
      comprised of four experimental groups. I. Uninfected controls (n = 8); II.
      Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional
      i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated
      bacteremia by treatment with serotype-specific anti-pneumococcal antibodies (n =
      14). T2 and diffusion weighted MR images were used to analyze changes in
      hippocampus volume and water diffusion (ADC). The results were correlated to ADC
      of the cortex, to ventricular volume, and to the extent of hippocampal apoptosis.
      RESULTS: Both ADC and the volume of hippocampus were significantly increased in
      meningitis rats compared to uninfected controls (Kruskal-Wallis test, p = 0.0001,
      Dunns Post Test, p < 0.05), and were significantly increased in meningitis rats
      with an early onset bacteremia as compared to meningitis rats with attenuated
      bacteremia (p < 0.05). Hippocampal ADC and the volume and size of brain
      ventricles were positively correlated (Spearman Rank, p < 0.05), whereas no
      association was found between ADC or volume and the extent of apoptosis (p >
      0.05). CONCLUSIONS: In experimental meningitis increase in volume and water
      diffusion of the hippocampus are significantly associated with accompanying
      bacteremia.

PMID- 24886046
TI  - Retention of female volunteer community health workers in Dhaka urban slums: a
      prospective cohort study.
AB  - BACKGROUND: Volunteer community health workers (CHWs) are a key approach to
      improving community-based maternal and child health services in developing
      countries. BRAC, a large Bangladeshi non-governmental organization (NGO), has
      employed female volunteer CHWs in its community-based health programs since 1977,
      recently including its Manoshi project, a community-based maternal and child
      health intervention in the urban slums of Bangladesh. A case-control study
      conducted in response to high dropout rates in the first year of the project
      showed that financial incentives, social prestige, community approval and
      household responsibilities were related to early retention in the project. In our
      present prospective cohort study, we aimed to better understand the factors
      associated with retention of volunteer CHWs once the project was more mature.
      METHODS: We used a prospective cohort study design to examine the factors
      affecting retention of volunteer CHWs who remained in the project after the
      initial start-up period. We surveyed a random sample of 542 CHWs who were working
      for BRAC Manoshi in December 2008. In December 2009, we revisited this cohort of
      CHWs and interviewed those who had dropped out about the main reasons for their
      dropping out. We used a multivariable generalized linear model regression
      analysis with a log link to estimate the relative risk (RR) of independent
      factors on retention. RESULTS: Of the 542 CHWs originally enrolled, 120 had
      dropped out by the end of one year, mainly because they left the slums. CHWs who
      received positive community appraisal (adjusted RR = 1.45, 95% confidence
      interval (CI) = 1.10 to 1.91) or were associated with other NGOs (adjusted RR =
      1.13, 95% CI = 1.04 to 1.23) were more likely to have been retained in the
      project. Although refresher training was also associated with increased retention
      (adjusted RR = 2.25, 95% CI = 1.08 to 4.71) in this study, too few CHWs had not
      attended refresher training regularly to make it a meaningful predictor of
      retention that could be applied in the project setting. CONCLUSION: Factors that
      affect retention of CHWs may change over time, with some factors that are
      important in the early years of a project losing importance as the project
      matures. Community health programs operating in fragile urban slums should
      consider changing factors over program duration for better retention of volunteer
      CHWs.

PMID- 24886047
TI  - The expression dynamics of IL-17 and Th17 response relative cytokines in the
      trachea and spleen of chickens after infection with Cryptosporidium baileyi.
AB  - BACKGROUND: Cryptosporidium baileyi is the dominant Cryptosporidium species in
      birds causing emerging health problems in the poultry industry, and is also a
      model to study the biology of Cryptosporidium spp.. IL-17 (also called IL-17A) is
      a hallmark pro-inflammatory cytokine of Th17 cells that plays an important role
      in several human autoimmune diseases and microbial infection disease of many
      animals, and it may play a role in Cryptosporidium infection. METHODS: The
      present study examined the mRNA level of IL-17 and Th17 response relative
      cytokines in the trachea and spleen of C. baileyi-infected chickens at different
      time points using real-time quantitative PCR (qPCR). RESULTS: All examined
      cytokines in the trachea were up-regulated in the infected chickens compared with
      the uninfected control during C. baileyi infection. Significant increased IL-17
      mRNA level in the trachea was observed as early as 12 h post infection (pi),
      peaking at 24 h pi and 10 d pi, and declining thereafter. The transcription
      levels of IL-17 and Th17 response relative cytokines in spleen were also
      significantly increased at different time points during the infection.
      CONCLUSIONS: IL-17 was indicated to participate in the induction of inflammation
      during infection of some intracellular protozoan parasites. The results in the
      present study suggest that IL-17 may play a role in immunity against
      Cryptosporidium infection, and provide basic information for determining the role
      of Th17 cell in Cryptosporidium infection.

PMID- 24886048
TI  - A systematic review of the use and effectiveness of social media in child health.
AB  - BACKGROUND: Social media use is highly prevalent among children, youth, and their
      caregivers, and its use in healthcare is being explored. The objective of this
      study was to conduct a systematic review to determine: 1) for what purposes
      social media is being used in child health and its effectiveness; and 2) the
      attributes of social media tools that may explain how they are or are not
      effective. METHODS: We searched Medline, CENTRAL, ERIC, PubMed, CINAHL, Academic
      Search Complete, Alt Health Watch, Health Source, Communication and Mass Media
      Complete, Web of Knowledge, and Proquest Dissertation and Theses Database from
      2000-2013. We included primary research that evaluated the use of a social media
      tool, and targeted children, youth, or their families or caregivers. Quality
      assessment was conducted on all included analytic studies using tools specific to
      different quantitative designs. RESULTS: We identified 25 studies relevant to
      child health. The majority targeted adolescents (64%), evaluated social media for
      health promotion (52%), and used discussion forums (68%). Most often, social
      media was included as a component of a complex intervention (64%). Due to
      heterogeneity in conditions, tools, and outcomes, results were not pooled across
      studies. Attributes of social media perceived to be effective included its use as
      a distraction in younger children, and its ability to facilitate communication
      between peers among adolescents. While most authors presented positive
      conclusions about the social media tool being studied (80%), there is little high
      quality evidence of improved outcomes to support this claim. CONCLUSIONS: This
      comprehensive review demonstrates that social media is being used for a variety
      of conditions and purposes in child health. The findings provide a foundation
      from which clinicians and researchers can build in the future by identifying
      tools that have been developed, describing how they have been used, and isolating
      components that have been effective.

PMID- 24886049
TI  - Leptin, adiponectin and serotonin levels in lean and obese dogs.
AB  - BACKGROUND: Serotonin (5-hydroytryptamine or 5HT) is associated with numerous
      behavioral and psychological factors and is a biochemical marker of mood. 5HT is
      involved in the hypothalamic regulation of energy consumption. 5HT controls
      appetite in the central nerve system (CNS) and stimulates intestinal mobility.
      There are few studies looking at the role of 5HT and the relationship between
      peripheral circulating serotonin and obesity. The aim of this study was to find
      any differences in leptin, adiponectin, and 5HT between lean and obese dogs and
      to identify correlations among these factors. RESULTS: Leptin, triglyceride (TG)
      and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin
      and 5HT levels were higher in the lean group compared to the obese group (p <
      0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r
      = 0.419, p < 0.01) were positively correlated with body condition score (BCS),
      and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were
      negatively correlated with BCS. Leptin was negatively correlated with adiponectin
      (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively
      correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and
      cholesterol (r = -0.357, p < 0.05). CONCLUSIONS: 5HT is an important appetite
      control neurotransmitter, but there are limited studies for 5HT levels related to
      obesity in dogs. To the best of our knowledge, this is the first study to
      evaluate peripheral 5HT levels in obese dogs. From this research, we can assume
      that 5HT may be correlated with canine obesity. Further studies will be needed to
      further elucidate the role of low serum 5HT levels in canine obesity.

PMID- 24886052
TI  - Stability and change in distress tolerance and its prospective relationship with
      borderline personality features: a short-term longitudinal study.
AB  - Distress tolerance (DT), or the ability to withstand psychological distress, has
      been proposed as a mechanism underlying multiple forms of psychopathology.
      However, research on DT is limited in several areas. First, stability and change
      of DT over time has never been assessed in adults. Second, it is unclear whether
      alternative conceptualizations of DT yield differences in longitudinal stability
      and change. Third, gender differences in DT have yet to be examined in
      nonclinical adult samples. And fourth, longitudinal predictive utility of DT has
      not been adequately assessed. The purpose of this study was to investigate these
      3 questions using data collected at 3 time points over a 6-month period,
      examining borderline personality disorder (BPD) features as an outcome. Using 3
      different measures of DT, results indicated that there is no mean level change in
      DT. Similarly, there was moderate rank-order stability in DT and no significant
      individual level change across measures. These findings suggest that DT is
      similar to other stable, trait-like constructs, as has been previously theorized.
      Next, a series of cross-lagged panel models revealed that although DT had a cross
      sectional relationship with BPD features across all time points, DT did not
      predict BPD traits longitudinally. These findings have implications for
      treatments for BPD.

PMID- 24886050
TI  - Small nucleolar RNA signatures of lung tumor-initiating cells.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is the number one cancer killer.
      Tumor-initiating cells (TICs) are responsible for tumor progression and
      recurrence. Emerging evidences suggest that small nucleolar RNAs (snoRNAs) play
      malfunctioning roles in lung tumorigenesis. This study aims to determine if
      snoRNAs have important function in lung TICs by: 1) profiling and comparing
      snoRNA expression patterns in lung ALDH1+/- cells of 28 primary NSCLC tissues to
      identify new signatures of TICs; 2) determining prognostic significance of the
      snoRNA signatures by analyzing the expression in 82 NSCLC tissues with different
      stages and histological types using quantitative PCR; 3) functionally
      investigating if the snoRNAs contribute to stemness of lung TICs using in vitro
      and in vivo assays. RESULTS: Twenty-two snoRNAs were identified whose changes
      were specific to the TICs. The expression of two snoRNAs (snoRA3 and snoRA42) was
      inversely associated with survival of NSCLC patients (P = 0.002, p = 0.001,
      respectively). Functional analysis indicated that snoRA42 was upregulated in
      CD133+ cells isolated from NSCLC cell lines compared with the CD133-
      counterparts. snoRA42 knockdown reduced the proliferation and self-renewal of
      TICs in vitro. However, ectopic expression of snoRA42 in non-TICs enhanced the
      potentials of cell proliferation and self-renewal. snoRA42 expression was
      associated with expression of stem cell-core transcription factors in lung TICs.
      Blocking snoRA42 expression in TIC xenografts decreased tumorigenesis in mice.
      CONCLUSIONS: The snoRNA signatures of lung TICs provide potential biomarkers for
      predicting outcome of NSCLC. snoRA42 is one of the important snoRNAs in
      regulating features of lung TICs, and thus contributes to lung tumorigenesis.

PMID- 24886051
TI  - Cost and burden of informal caregiving of dependent older people in a rural
      Indian community.
AB  - BACKGROUND: Lack of state supported care services begets the informal caregiving
      by family members as the mainstay of care provided to the dependent older people
      in many Low and Middle Income Countries (LMICs), including India. Little is known
      about the time spent on caregiving, its cost and the burden experienced by these
      informal caregivers. We aimed to estimate the costs of informal caregiving and to
      evaluate the nature as well as correlates of caregivers' burden in a rural Indian
      community. METHODS: We assessed 1000 people aged above 65 years, among whom 85
      were dependent. We assessed their socioeconomic profiles, disability, health
      status and health expenditures. Their caregivers' socio-demographic profiles,
      mental health, and the time spent on caregiving were assessed using standard
      instruments. Caregiver's burden was evaluated using Zarit Burden Scale. We valued
      the annual informal caregiving costs using proxy good method. We employed
      appropriate non-parametric multivariate statistics to evaluate the correlates of
      caregivers' burden. RESULTS: Average time spent on informal caregiving was 38.6
      (95% CI 35.3-41.9) hours/week. Estimated annual cost of informal caregiving using
      proxy good method was 119,210 US$ in this rural community. Mean total score of
      Zarit burden scale, measuring caregivers' burden, was 17.9 (95% CI 15.6-20.2).
      Prevalence of depression among the caregivers was 10.6% (95% CI 4.1-17.1%).
      Cerebrovascular disease, Parkinson's disease, higher disability, insomnia and
      incontinence of the dependent older people as well as the time spent on helping
      Activities of Daily Living and on supervision increased caregiver's burden
      significantly. CONCLUSIONS: Cost and burden of informal caregiving are high in
      this rural Indian community. Many correlates of burden, experienced by
      caregivers, are modifiable. We discuss potential strategies to reduce this burden
      in LMICs. Need for support to informal caregivers and for management of dependent
      older people with chronic disabling diseases by multidisciplinary community teams
      are highlighted.

PMID- 24886053
TI  - A closer look at the lower-order structure of the Personality Inventory for DSM
      5: comparison with the Five-Factor Model.
AB  - The Personality Inventory for DSM-5 (PID-5) was developed as a measure of the
      maladaptive personality trait model included within Section III of the DSM-5.
      Although preliminary findings have suggested the PID-5 has a five-factor
      structure that overlaps considerably with the Five-Factor Model (FFM) at the
      higher order level, there has been much less attention on the specific locations
      of the 25 lower-order traits. Joint exploratory factor analysis of the PID-5
      traits and the 30 facets of the NEO-PI-R were used to determine the lower-order
      structure of the PID-5. Results indicated the PID-5's domain-level structure
      closely resembled the FFM. We also explored the placement of several lower-order
      facets that have not loaded consistently in previous studies. Overall, these
      results indicate that the PID-5 shares a common structure with the FFM and
      clarify the placement of some interstitial facets. More research investigating
      the lower-order facets is needed to determine how they fit into the hierarchical
      structure and explicate their relationships to existing measures of pathological
      traits.

PMID- 24886054
TI  - Optimizing strategies for meningococcal C disease vaccination in Valencia
      (Spain).
AB  - BACKGROUND: Meningococcal C (MenC) conjugate vaccines have controlled invasive
      diseases associated with this serogroup in countries where they are included in
      National Immunization Programs and also in an extensive catch-up program
      involving subjects up to 20 years of age. Catch-up was important, not only
      because it prevented disease in adolescents and young adults at risk, but also
      because it decreased transmission of the bacteria, since it was in this age group
      where the organism was circulating. Our objective is to develop a new vaccination
      schedule to achieve maximum seroprotection in these groups. METHODS: A recent
      study has provided detailed age-structured information on the seroprotection
      levels against MenC in Valencia (Spain), where vaccination is routinely scheduled
      at 2 months and 6 months, with a booster dose at 18 months of age. A
      complementary catch-up campaign was also carried out in n for children from 12
      months to 19 years of age. Statistical analyses of these data have provided an
      accurate picture on the evolution of seroprotection in the last few years.
      RESULTS: An agent-based model has been developed to study the future evolution of
      the seroprotection histogram. We have shown that the optimum strategy for
      achieving high protection levels in all infants, toddlers and adolescents is a
      change to a 2 months, 12 months and 12 years of age vaccination pattern. If the
      new schedule were implemented in January 2014, high-risk subjects between 15-19
      years of age would have very low seroprotection for the next 6 years, thereby
      threatening the program. CONCLUSIONS: High protection levels and a low incidence
      of meningococcal C disease can be achieved in the future by means of a cost-free
      change in vaccination program. However, we recommend a new catch-up program
      simultaneous to the change in regular vaccination program.

PMID- 24886055
TI  - Characteristics of TCM constitutions of adult Chinese women in Hong Kong and
      identification of related influencing factors: a cross-sectional survey.
AB  - BACKGROUND: Traditional Chinese Medicine Constitution (TCMC) refers to an
      integrated, metastable and natural specialty of individual in morphosis,
      physiological functions and psychological conditions. It is formed on the basis
      of innate and acquired endowments in the human life process, which can be divided
      into normal constitution and unbalanced ones. The aim of this study was to
      investigate the distribution of TCMCs of Chinese women in Hong Kong and its
      acquired influencing factors. METHODS: Local Chinese women between 30 to 65 years
      old, were recruited from 18 districts of Hong Kong (n=944), and were assessed
      using the Traditional Chinese Medicine Physical Constitution Scale for their TCMC
      types. Social-demographic, reproductive, lifestyle, systemic health and emotional
      status information were collected through structured questionnaire. The
      associations between different independent factors and each TCMC type, as well as
      the complex unbalanced TCMC types were tested individually. Significant factors
      related to unbalanced TCMC types were identified in final models using multiple
      factor analysis. RESULTS: A total of 764 (80.9%) participants were diagnosed with
      unbalanced TCMCs. The most common TCMC type was Qi-deficiency constitution
      (53.9%), followed by Phlegm-wetness (38.9%), Yang-deficiency (38.2%), Yin
      deficiency (35.5), Blood-stasis (35.4) and Qi-depressed (31%) constitution. Six
      hundred and eleven participants (64.7%) had at least two types of combined and
      unbalanced constitutions. Stepwise logistic analysis indicated that poor systemic
      health condition (OR, 1.76-2.89), negative emotions (OR=1.39), overweight
      (OR=1.58), high educational level (OR=1.18) and mental work (OR=1.44) were
      significantly positively correlated with certain unbalanced TCMCs. Meanwhile,
      aging (OR, 0.59-0.73), exercise habit (OR, 0.61-0.79) and reproductive history
      (OR=0.72) showed inverse associations with unbalanced constitutions. In addition,
      systemic health condition and emotional status, exercise habit and age were
      significantly associated with the combined unbalanced TCMC types. CONCLUSION: The
      majority of middle-aged Chinese women in Hong Kong had unbalanced and complex
      TCMCs. Qi-deficiency, Phlegm-wetness and Yang-deficiency constitutions are the
      most common constitutions. Poor systemic health condition, less-than-satisfactory
      emotional life, overweight and mental work are associated with and may be
      contributors for the formation of unbalanced TCMCs, while regular physical
      exercise was found to be a potential protective factor for unbalanced TCMCs.

PMID- 24886056
TI  - A combined model of human erythropoiesis and granulopoiesis under growth factor
      and chemotherapy treatment.
AB  - BACKGROUND: Haematotoxicity of conventional chemotherapies often results in
      delays of treatment or reduction of chemotherapy dose. To ameliorate these side
      effects, patients are routinely treated with blood transfusions or haematopoietic
      growth factors such as erythropoietin (EPO) or granulocyte colony-stimulating
      factor (G-CSF). For the latter ones, pharmaceutical derivatives are available,
      which differ in absorption kinetics, pharmacokinetic and -dynamic properties. Due
      to the complex interaction of cytotoxic effects of chemotherapy and the
      stimulating effects of different growth factor derivatives, optimal treatment is
      a non-trivial task. In the past, we developed mathematical models of
      thrombopoiesis, granulopoiesis and erythropoiesis under chemotherapy and growth
      factor applications which can be used to perform clinically relevant predictions
      regarding the feasibility of chemotherapy schedules and cytopenia prophylaxis
      with haematopoietic growth factors. However, interactions of lineages and growth
      factors were ignored so far. RESULTS: To close this gap, we constructed a hybrid
      model of human granulopoiesis and erythropoiesis under conventional chemotherapy,
      G-CSF and EPO applications. This was achieved by combining our single lineage
      models of human erythropoiesis and granulopoiesis with a common stem cell model.
      G-CSF effects on erythropoiesis were also implemented. Pharmacodynamic models are
      based on ordinary differential equations describing proliferation and maturation
      of haematopoietic cells. The system is regulated by feedback loops partly
      mediated by endogenous and exogenous EPO and G-CSF. Chemotherapy is modelled by
      depletion of cells. Unknown model parameters were determined by fitting the model
      predictions to time series data of blood counts and cytokine profiles. Data were
      extracted from literature or received from cooperating clinical study groups. Our
      model explains dynamics of mature blood cells and cytokines after growth-factor
      applications in healthy volunteers. Moreover, we modelled 15 different
      chemotherapeutic drugs by estimating their bone marrow toxicity. Taking into
      account different growth-factor schedules, this adds up to 33 different
      chemotherapy regimens explained by the model. CONCLUSIONS: We conclude that we
      established a comprehensive biomathematical model to explain the dynamics of
      granulopoiesis and erythropoiesis under combined chemotherapy, G-CSF, and EPO
      applications. We demonstrate how it can be used to make predictions regarding
      haematotoxicity of yet untested chemotherapy and growth-factor schedules.

PMID- 24886057
TI  - Viral metagenomic analysis of feces of wild small carnivores.
AB  - BACKGROUND: Recent studies have clearly demonstrated the enormous virus diversity
      that exists among wild animals. This exemplifies the required expansion of our
      knowledge of the virus diversity present in wildlife, as well as the potential
      transmission of these viruses to domestic animals or humans. METHODS: In the
      present study we evaluated the viral diversity of fecal samples (n = 42)
      collected from 10 different species of wild small carnivores inhabiting the
      northern part of Spain using random PCR in combination with next-generation
      sequencing. Samples were collected from American mink (Neovison vison), European
      mink (Mustela lutreola), European polecat (Mustela putorius), European pine
      marten (Martes martes), stone marten (Martes foina), Eurasian otter (Lutra lutra)
      and Eurasian badger (Meles meles) of the family of Mustelidae; common genet
      (Genetta genetta) of the family of Viverridae; red fox (Vulpes vulpes) of the
      family of Canidae and European wild cat (Felis silvestris) of the family of
      Felidae. RESULTS: A number of sequences of possible novel viruses or virus
      variants were detected, including a theilovirus, phleboviruses, an amdovirus, a
      kobuvirus and picobirnaviruses. CONCLUSIONS: Using random PCR in combination with
      next generation sequencing, sequences of various novel viruses or virus variants
      were detected in fecal samples collected from Spanish carnivores. Detected novel
      viruses highlight the viral diversity that is present in fecal material of wild
      carnivores.

PMID- 24886058
TI  - Popliteal lymph node dissection for metastases of cutaneous malignant melanoma.
AB  - Popliteal lymph node dissection is performed when grossly metastatic nodal
      disease is encountered in the popliteal fossa or after microscopic metastasis is
      found in interval sentinel nodes during clinical staging of cutaneous malignant
      melanoma. Initially, an S-shaped incision is made to gain access to the popliteal
      fossa. A careful en bloc removal of fat tissue and lymph nodes is made to
      preserve and avoid the injury of peroneal and tibial nerves as well as popliteal
      vessels, following the previous recommendations. This rare surgical procedure was
      successfully employed in a patient with cutaneous malignant melanoma and nodal
      metastases at the popliteal fossa. The technique described by Karakousis was
      reproduced in a step-by-step fashion to allow anatomical identification of the
      neurovascular structures and radical resection with no post-operative morbidity
      and prompt recovery. Popliteal lymph node dissection is a rarely performed
      operative procedure. Following a lymphoscintigraphic examination of the popliteal
      nodal station, surgeons can be asked to explore the popliteal fossa. Detailed
      familiarity of the operative procedure is necessary, however, to avoid
      complications. 

PMID- 24886059
TI  - Assessing the robustness of passive scattering proton therapy with regard to
      local recurrence in stage III non-small cell lung cancer: a secondary analysis of
      a phase II trial.
AB  - BACKGROUND: We assessed the robustness of passive scattering proton therapy
      (PSPT) plans for patients in a phase II trial of PSPT for stage III non-small
      cell lung cancer (NSCLC) by using the worst-case scenario method, and compared
      the worst-case dose distributions with the appearance of locally recurrent
      lesions. METHODS: Worst-case dose distributions were generated for each of 9
      patients who experienced recurrence after concurrent chemotherapy and PSPT to 74
      Gy(RBE) for stage III NSCLC by simulating and incorporating uncertainties
      associated with set-up, respiration-induced organ motion, and proton range in the
      planning process. The worst-case CT scans were then fused with the positron
      emission tomography (PET) scans to locate the recurrence. RESULTS: Although the
      volumes enclosed by the prescription isodose lines in the worst-case dose
      distributions were consistently smaller than enclosed volumes in the nominal
      plans, the target dose coverage was not significantly affected: only one patient
      had a recurrence outside the prescription isodose lines in the worst-case plan.
      CONCLUSIONS: PSPT is a relatively robust technique. Local recurrence was not
      associated with target underdosage resulting from estimated uncertainties in 8 of
      9 cases.

PMID- 24886060
TI  - Use of NQO1 status as a selective biomarker for oesophageal squamous cell
      carcinomas with greater sensitivity to 17-AAG.
AB  - BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) is a major health burden
      in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat
      this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17
      demethoxygeldanamycin (17-AAG) has previously been proposed as a possible
      candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the
      potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell
      lines in the context of their NQO1 status. METHODS: We used MTT assays to compare
      the sensitivity of a panel of OSCC cell lines to 17-AAG. Western blotting, and RT
      PCR were used to investigate NQO1 protein and mRNA levels, while an RFLP approach
      was used to investigate the NQO1 C609T SNP. RESULTS: Expression of NQO1 markedly
      increased sensitivity to 17-AAG in the OSCC cell lines, while normal fibroblasts,
      which expressed HSP90 at much lower levels, were more resistant to 17-AAG. In
      isolation, neither the C609T SNP, nor NQO1 mRNA levels was an accurate predictor
      of NQO1 protein levels. CONCLUSIONS: Since NQO1 greatly enhances the anti-cancer
      effects of 17-AAG, this could be used as a selective marker for patients that
      would benefit most from 17-AAG chemotherapy at low doses. Testing for the
      presence of the C609T SNP in both alleles could be used as a screen to exclude
      potentially poor responders to 17-AAG treatment at low dosages.

PMID- 24886061
TI  - Food, home and health: the meanings of food amongst Bengali Women in London.
AB  - BACKGROUND: This paper explores the nature of food and plants and their meanings
      in a British Bengali urban context. It focuses on the nature of plants and food
      in terms of their role in home making, transnational connections, generational
      change and concepts of health. METHODS: An ethnographic approach to the research
      was taken, specific methods included participant observation, focus group
      discussions and semi-structured interviews. Thirty women of Bengali origin were
      mostly composed of "mother" and "daughter" pairs. The mothers were over 45 years
      old and had migrated from Bangladesh as adults and their grown-up daughters grew
      up in the UK. RESULTS: Food and plants play an important role in the construction
      of home "here" (London) while continuing to connect people to home "there"
      (Sylhet). This role, however, changes and is re-defined across generations.
      Looking at perceptions of "healthy" and "unhealthy" food, particularly in the
      context of Bengali food, multiple views of what constitutes "healthy" food exist.
      However, there appeared to be little two-way dialogue about this concept between
      the research participants and health professionals. This seems to be based on
      "cultural" and power differences that need to be addressed for a meaningful
      dialogue to occur. CONCLUSION: In summary, this paper argues that while food is
      critical to the familial spaces of home (both locally and globally), it is
      defined by a complex interplay of actors and wider meanings as illustrated by
      concepts of health and what constitutes Bengali food. Therefore, we call for
      greater dialogue between health professionals and those they interact with, to
      allow for an enhanced appreciation of the dynamic nature of food and plants and
      the diverse perceptions of the role that they play in promoting health.

PMID- 24886062
TI  - A focus group study of healthy eating knowledge, practices, and barriers among
      adult and adolescent immigrants and refugees in the United States.
AB  - BACKGROUND: Immigrants and refugees to the United States exhibit lower dietary
      quality than the general population, but reasons for this disparity are poorly
      understood. In this study, we describe the meanings of food, health and wellbeing
      through the reported dietary preferences, beliefs, and practices of adults and
      adolescents from four immigrant and refugee communities in the Midwestern United
      States. METHODS: Using a community based participatory research approach, we
      conducted a qualitative research study with 16 audio-recorded focus groups with
      adults and adolescents who self-identified as Mexican, Somali, Cambodian, and
      Sudanese. Focus group topics were eating patterns, perceptions of healthy eating
      in the country of origin and in the U.S., how food decisions are made and who in
      the family is involved in food preparation and decisions, barriers and
      facilitators to healthy eating, and gender and generational differences in eating
      practices. A team of investigators and community research partners analyzed all
      transcripts in full before reducing data to codes through consensus. Broader
      themes were created to encompass multiple codes. RESULTS: Results show that
      participants have similar perspectives about the barriers (personal,
      environmental, structural) and benefits of healthy eating (e.g., 'junk food is
      bad'). We identified four themes consistent across all four communities: Ways of
      Knowing about Healthy Eating ('Meanings;' 'Motivations;' 'Knowledge Sources'),
      Eating Practices ('Family Practices;' 'Americanized Eating Practices' 'Eating
      What's Easy'), Barriers ('Taste and Cravings;' 'Easy Access to Junk Food;' 'Role
      of Family;' Cultural Foods and Traditions;' 'Time;' 'Finances'), and Preferences
      for Intervention ('Family Counseling;' Community Education;' and 'Healthier
      Traditional Meals.'). Some generational (adult vs. adolescents) and gender
      differences were observed. CONCLUSIONS: Our study demonstrates how personal,
      structural, and societal/cultural factors influence meanings of food and dietary
      practices across immigrant and refugee populations. We conclude that cultural
      factors are not fixed variables that occur independently from the contexts in
      which they are embedded.

PMID- 24886063
TI  - Mining the pre-diagnostic antibody repertoire of TgMMTV-neu mice to identify
      autoantibodies useful for the early detection of human breast cancer.
AB  - BACKGROUND: The use of autoantibodies for the early detection of breast cancer
      has generated much interest as antibodies can be readily assayed in serum when
      antigen levels are low. Ideally, diagnostic autoantibodies would be identified in
      individuals who harbored pre-invasive disease/high risk lesions leading to
      malignancy. Prospectively collected human serum samples from these individuals
      are rare and not often available for biomarker discovery. We questioned whether
      transgenic animals could be used to identify cancer-associated autoantibodies
      present at the earliest stages of the malignant transformation of breast cancer.
      METHODS: We collected sera from transgenic mice (TgMMTV-neu) from the time of
      birth to death by spontaneous mammary tumors. Using sera from a time point prior
      to the development of tumor, i.e. "pre-diagnostic", we probed cDNA libraries
      derived from syngeneic tumors to identify proteins recognized by IgG antibodies.
      Once antigens were identified, selected proteins were evaluated via protein
      arrays, for autoantibody responses using plasma from women obtained prior to the
      development of breast cancer and matched controls. The ability of the antigens to
      discriminate cases from controls was assessed using receiver-operating
      characteristic curve analyses and estimates of the area under the curve. RESULTS:
      We identified 6 autoantibodies that were present in mice prior to the development
      of mammary cancer: Pdhx, Otud6b, Stk39, Zpf238, Lgals8, and Vps35. In rodent
      validation cohorts, detecting both IgM and IgG antibody responses against a
      subset of the identified proteins could discriminate pre-diagnostic sera from non
      transgenic control sera with an AUC of 0.924. IgG and IgM autoantibodies,
      specific for a subset of the identified antigens, could discriminate the samples
      of women who eventually developed breast cancer from case-matched controls who
      did not develop disease. The discriminatory potential of the pre-diagnostic
      autoantibodies was enhanced if plasma samples were collected greater than 5
      months prior to a breast cancer diagnosis (AUC 0.68; CI 0.565-0.787, p=0.0025).
      CONCLUSION: Genetically engineered mouse models of cancer may provide a facile
      discovery tool for identifying autoantibodies useful for human cancer
      diagnostics.

PMID- 24886064
TI  - The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial
      of tenecteplase vs. alteplase in acute ischaemic stroke.
AB  - BACKGROUND: Alteplase is the only approved thrombolytic agent for acute ischaemic
      stroke. The overall benefit from alteplase is substantial, but some evidence
      indicates that alteplase also has negative effects on the ischaemic brain.
      Tenecteplase may be more effective and less harmfull than alteplase, but large
      randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase
      Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs.
      alteplase. METHODS/DESIGN: NOR-TEST is a multi-centre PROBE (prospective
      randomised, open-label, blinded endpoint) trial designed to establish superiority
      of tenecteplase 0.4 mg/kg (single bolus) as compared with alteplase 0.9 mg/kg
      (10% bolus + 90% infusion/60 minutes) for consecutively admitted patients with
      acute ischaemic stroke eligible for thrombolytic therapy, i.e. patients a)
      admitted <41/2 hours after symptoms onset; b) admitted <41/2 hours after
      awakening with stroke symptoms c) receiving bridging therapy before
      embolectomy.Randomisation tenecteplase:alteplase is 1:1. The primary study
      endpoint is favourable functional outcome defined as modified Rankin Scale 0-1 at
      90 days. Secondary study endpoints are: 1) haemorrhagic transformation
      (haemorrhagic infarct/haematoma); 2) symptomatic cerebral haemorrhage on CT 24-48
      hours; 3) major neurological improvement at 24 hours; 4) recanalisation at 24-36
      hours; 5) death. DISCUSSION: NOR-TEST may establish a novel approach to acute
      ischaemic stroke treatment. A positive result will lead to a more effective,
      safer and easier treatment for all acute ischaemic stroke pasients.NOR-TEST is
      reviewed and approved by the Regional Committee for Medical and Health Research
      Ethics (2011/2435), and The Norwegian Medicines Agency (12/01402). NOR-TEST is
      registered with EudraCT No 2011-005793-33 and in ClinicalTrials.gov
      (NCT01949948).

PMID- 24886065
TI  - Prostate volume and biopsy tumor length are significant predictors for classical
      and redefined insignificant cancer on prostatectomy specimens in Japanese men
      with favorable pathologic features on biopsy.
AB  - BACKGROUND: Gleason pattern 3 less often has molecular abnormalities and often
      behaves indolent. It is controversial whether low grade small foci of prostate
      cancer (PCa) on biopsy could avoid immediate treatment or not, because
      substantial cases harbor unfavorable pathologic results on prostatectomy
      specimens. This study was designed to identify clinical predictors for classical
      and redefined insignificant cancer on prostatectomy specimens in Japanese men
      with favorable pathologic features on biopsy. METHODS: Retrospective review of
      1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013.
      Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage <=
      cT2a, Gleason score (GS) <= 6, up to two positive biopsies, and no more than 50%
      of cancer involvement in any core. The associations between preoperative data and
      unfavorable pathologic results of prostatectomy specimens, and oncological
      outcome were analyzed. The definition of insignificant cancer consisted of
      pathologic stage <= pT2, GS <= 6, and an index tumor volume < 0.5 mL (classical)
      or 1.3 mL (redefined). RESULTS: Pathologic stage >= pT3, upgraded GS, index tumor
      volume >= 0.5 mL, and >= 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83
      (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had
      classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year
      recurrence-free survival was 86.8%, and the insignificant cancers essentially did
      not relapse regardless of the surgical margin status. MRI-estimated prostate
      volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and
      findings of magnetic resonance imaging were associated with the presence of
      classical and redefined insignificant cancer. Large prostate volume and short
      tumor length on biopsy remained as independent predictors in multivariate
      analysis. CONCLUSIONS: Favorable features of biopsy often are followed by adverse
      pathologic findings on prostatectomy specimens despite fulfilling the established
      criteria. The finding that prostate volume is important does not simply mirror
      many other studies showing PSAD is important, and the clinical criteria for risk
      assessment before definitive therapy or active surveillance should incorporate
      these significant factors other than clinical T-staging or PSAD to minimize under
      estimation of cancer in Japanese patients with low-risk PCa.

PMID- 24886067
TI  - A simple new technique for the removal of fractured femoral stems: a case report.
AB  - INTRODUCTION: The removal of broken femoral stems has become a major issue in
      revision surgery, and is a technically difficult and time-consuming procedure.
      CASE PRESENTATION: We present a case of a fracture of a cementless long femoral
      stem in a 65-year-old, white Caucasian man. The distal part was removed with a
      special longitudinal osteotomy through the anterior cortex extending distally for
      10 cm. It was then followed by a transversal osteotomy 2 cm below the tip of the
      femoral stump to allow enough space for two locking pliers. Simultaneously using
      a lamina spreader on the distal part, the broken stem was extracted while
      hammering on two locking pliers. CONCLUSIONS: We developed a simple and easy
      technique for the removal of a broken femoral stem that can be applied to all
      kinds of femoral stems and intramedullary nails regardless of their cross
      section. We used ordinary surgical instruments and spared the remaining bone
      stock.

PMID- 24886066
TI  - Usefulness of C-reactive protein testing in acute cough/respiratory tract
      infection: an open cluster-randomized clinical trial with C-reactive protein
      testing in the intervention group.
AB  - BACKGROUND: Point of care testing for C-reactive protein (CRP) has shown promise
      as a measure to reduce unnecessary antibiotic prescribing in respiratory tract
      infections (RTI), but its use in primary care is still controversial. We aimed to
      evaluate the effect of CRP testing on the prescription of antibiotics, referral
      for radiography, and the outcome of patients in general practice with acute
      cough/RTI. METHODS: An open-cluster randomized clinical trial was conducted, with
      CRP testing performed in the intervention group. Antibiotic prescribing and
      referral for radiography were the main outcome measures. RESULTS: A total of 179
      patients were included: 101 in the intervention group and 78 in the control
      group. The two groups were similar in clinical characteristics. In the
      intervention group, the antibiotic prescribing rate was 37.6%, which was
      significantly lower than that in the control group (58.9%) (P=0.006). Referral
      for chest X-ray was also significantly lower in the intervention group (55.4%)
      than in the control group (75.6%) (P=0.004). The recovery rate, as recorded by
      the GPs, was 92.9% and 93.6% in the intervention and control groups,
      respectively. CONCLUSION: The study showed that CRP testing in patients with
      acute cough/RTI may reduce antibiotic prescribing and referral for radiography,
      probably without compromising recovery. TRIAL REGISTRATION: The trial was
      registered in the ClinicalTrials.gov Protocol Registration System (identification
      number: NCT01794819).

PMID- 24886068
TI  - Discovery of novel enzymes with industrial potential from a cold and alkaline
      environment by a combination of functional metagenomics and culturing.
AB  - BACKGROUND: The use of cold-active enzymes has many advantages, including reduced
      energy consumption and easy inactivation. The ikaite columns of SW Greenland are
      permanently cold (4-6 degrees C) and alkaline (above pH 10), and the
      microorganisms living there and their enzymes are adapted to these conditions.
      Since only a small fraction of the total microbial diversity can be cultured in
      the laboratory, a combined approach involving functional screening of a strain
      collection and a metagenomic library was undertaken for discovery of novel
      enzymes from the ikaite columns. RESULTS: A strain collection with 322 cultured
      isolates was screened for enzymatic activities identifying a large number of
      enzyme producers, with a high re-discovery rate to previously characterized
      strains. A functional expression library established in Escherichia coli
      identified a number of novel cold-active enzymes. Both alpha-amylases and beta
      galactosidases were characterized in more detail with respect to temperature and
      pH profiles and one of the beta-galactosidases, BGalI17E2, was able to hydrolyze
      lactose at 5 degrees C. A metagenome sequence of the expression library indicated
      that the majority of enzymatic activities were not detected by functional
      expression. Phylogenetic analysis showed that different bacterial communities
      were targeted with the culture dependent and independent approaches and revealed
      the bias of multiple displacement amplification (MDA) of DNA isolated from
      complex microbial communities. CONCLUSIONS: Many cold- and/or alkaline-active
      enzymes of industrial relevance were identified in the culture based approach and
      the majority of the enzyme-producing isolates were closely related to previously
      characterized strains. The function-based metagenomic approach, on the other
      hand, identified several enzymes (beta-galactosidases, alpha-amylases and a
      phosphatase) with low homology to known sequences that were easily expressed in
      the production host E. coli. The beta-galactosidase BGalI17E2 was able to
      hydrolyze lactose at low temperature, suggesting a possibly use in the dairy
      industry for this enzyme. The two different approaches complemented each other by
      targeting different microbial communities, highlighting the usefulness of
      combining methods for bioprospecting. Finally, we document here that ikaite
      columns constitute an important source of cold- and/or alkaline-active enzymes
      with industrial application potential.

PMID- 24886069
TI  - Comments on "detection of Toxoplasma gondii in raw caprine, ovine, buffalo,
      bovine, and camel milk using cell cultivation, cat bioassay, capture ELISA, and
      PCR methods in Iran".

PMID- 24886070
TI  - Pharmacokinetics, clearance, and biosafety of polyethylene glycol-coated hollow
      gold nanospheres.
AB  - OBJECTIVE: Gold nanoparticles have attracted enormous interest as potential
      theranostic agents. However, little is known about the long-term elimination and
      systemic toxicity of gold nanoparticles in the literature. Hollow gold
      nanospheres (HAuNS) is a class of photothermal conducting agent that have shown
      promises in photoacoustic imaging, photothermal ablation therapy, and drug
      delivery. It's very necessary to make clear the biosafety of HAuNS for its
      further application. METHODS: We investigated the cytotoxicity, complement
      activation, and platelet aggregation of polyethylene glycol (PEG)-coated HAuNS
      (PEG-HAuNS, average diameter of 63 nm) in vitro and their pharmacokinetics,
      biodistribution, organ elimination, hematology, clinical chemistry, acute
      toxicity, and chronic toxicity in mice. RESULTS: PEG-HAuNS did not induce
      detectable activation of the complement system and did not induce detectable
      platelet aggregation. The blood half-life of PEG-HAuNS in mice was 8.19 +/- 1.4
      hr. The single effective dose of PEG-HAuNS in photothermal ablation therapy was
      determined to be 12.5 mg/kg. PEG-HAuNS caused no adverse effects after 10 daily
      intravenous injections over a 2-week period at a dose of 12.5 mg/kg per injection
      (accumulated dose: 125 mg/kg). Quantitative analysis of the muscle, liver,
      spleen, and kidney revealed that the levels of Au decreased 45.2%, 28.6%, 41.7%,
      and 40.8%, respectively, from day 14 to day 90 after the first intravenous
      injection, indicating that PEG-HAuNS was slowly cleared from these organs in
      mice. CONCLUSION: Our data support the use of PEG-HAuNS as a promising
      photothermal conducting agent.

PMID- 24886072
TI  - The development of an online decision support tool for organizational readiness
      for change.
AB  - BACKGROUND: Much importance has been placed on assessing readiness for change as
      one of the earliest steps of implementation, but measuring it can be a complex
      and daunting task. Organizations and individuals struggle with how to reliably
      and accurately measure readiness for change. Several measures have been developed
      to help organizations assess readiness, but these are often underused due to the
      difficulty of selecting the right measure. In response to this challenge, we will
      develop and test a prototype of a decision support tool that is designed to guide
      individuals interested in implementation in the selection of an appropriate
      readiness assessment measure for their setting. METHODS: A multi-phase approach
      will be used to develop the decision support tool. First, we will identify key
      measures for assessing organizational readiness for change from a recently
      completed systematic review. Included measures will be those developed for
      healthcare settings (e.g., acute care, public health, mental health) and that
      have been deemed valid and reliable. Second, study investigators and field
      experts will engage in a mapping exercise to categorize individual items of
      included measures according to key readiness constructs from an existing
      framework. Third, a stakeholder panel will be recruited and consulted to
      determine the feasibility and relevance of the selected measures using a modified
      Delphi process. Fourth, findings from the mapping exercise and stakeholder
      consultation will inform the development of a decision support tool that will
      guide users in appropriately selecting change readiness measures. Fifth, the tool
      will undergo usability testing. DISCUSSION: Our proposed decision support tool
      will address current challenges in the field of organizational change readiness
      by aiding individuals in selecting a valid and reliable assessment measure that
      is relevant to user needs and practice settings. We anticipate that implementers
      and researchers who use our tool will be more likely to conduct readiness for
      change assessments in their settings when planning for implementation. This, in
      turn, may contribute to more successful implementation outcomes. We will test
      this tool in a future study to determine its efficacy and impact on
      implementation processes.

PMID- 24886071
TI  - Genetic characterization of the human relapsing fever spirochete Borrelia
      miyamotoi in vectors and animal reservoirs of Lyme disease spirochetes in France.
AB  - BACKGROUND: In France as elsewhere in Europe the most prevalent TBD in humans is
      Lyme borreliosis, caused by different bacterial species belonging to Borrelia
      burgdorferi sensu lato complex and transmitted by the most important tick species
      in France, Ixodes ricinus. However, the diagnosis of Lyme disease is not always
      confirmed and unexplained syndromes occurring after tick bites have become an
      important issue. Recently, B. miyamotoi belonging to the relapsing fever group
      and transmitted by the same Ixodes species has been involved in human disease in
      Russia, the USA and the Netherlands. In the present study, we investigate the
      presence of B. miyamotoi along with other Lyme Borreliosis spirochetes, in ticks
      and possible animal reservoirs collected in France. METHODS: We analyzed 268
      ticks (Ixodes ricinus) and 72 bank voles (Myodes glareolus) collected and trapped
      in France for the presence of DNA from B. miyamotoi as well as from Lyme
      spirochetes using q-PCR and specific primers and probes. We then compared the
      French genotypes with those found in other European countries. RESULTS: We found
      that 3% of ticks and 5.55% of bank voles were found infected by the same B.
      miyamotoi genotype, while co-infection with other Lyme spirochetes (B. garinii)
      was identified in 12% of B. miyamotoi infected ticks. Sequencing showed that
      ticks and rodents carried the same genotype as those recently characterized in a
      sick person in the Netherlands. CONCLUSIONS: The genotype of B. miyamotoi
      circulating in ticks and bank voles in France is identical to those already
      described in ticks from Western Europe and to the genotype isolated from a sick
      person in The Netherlands. This results suggests that even though no human cases
      have been reported in France, surveillance has to be improved. Moreover, we
      showed that ticks could simultaneously carry B. miyamotoi and Lyme disease
      spirochetes, increasing the problem of co-infection in humans.

PMID- 24886073
TI  - Individual quality explains association between plumage colouration, arrival
      dates and mate acquisition in yellow warblers (Setophaga petechia).
AB  - BACKGROUND: In many bird species colour traits influence social dominance and
      breeding success. In our study we first evaluated whether the colour of the basic
      plumage (tail feathers grown at the end of the breeding season), that provides an
      index of individual quality, influenced winter habitat use by yellow warblers. We
      then evaluated whether winter habitat use (inferred using delta13C and delta15N
      signatures of winter grown greater-coverts) influenced alternate plumage
      colouration, after controlling for individual quality using basic plumage
      colouration. Finally, we investigated whether basic and alternate plumage
      colouration influenced arrival dates, mate acquisition, breeding phenology and
      reproductive success of yellow warblers breeding in southern (Revelstoke, B.C.)
      and arctic (Inuvik, N.W.T.) Canada. RESULTS: The colour (chroma and hue) of tail
      feathers, grown on the breeding grounds, was not related to subsequent winter
      habitat use. Greater covert and tail feather colour (chroma and hue) were
      correlated, suggesting genetics and/or individual quality played a role in
      pigment deposition. After controlling for individual difference in tail colour,
      delta13C values did not explain any variation in greater covert colour, but birds
      with high delta15N signatures had greater coverts with higher chroma. Male
      arrival dates varied with tail chroma in Revelstoke and tail hue in Inuvik. Males
      that arrived early paired with older and/or more colourful mates that initiated
      clutches earlier, and at one site (Revelstoke) were more likely to fledge young.
      In addition, in Revelstoke (but not Inuvik) males with high tail hue also
      acquired more colourful mates. In contrast, after controlling for individual
      differences in tail colour, greater covert colour did not affect male arrival
      date, the quality of the mate obtained or reproductive success in either
      population. CONCLUSIONS: Our results suggest that plumage colour effects on
      breeding phenology and mate acquisition result from differences in the intrinsic
      quality of individuals rather than a carry-over effect of winter habitat use.

PMID- 24886074
TI  - A lactate shuttle system between tumour and stromal cells is associated with poor
      prognosis in prostate cancer.
AB  - BACKGROUND: In a malignant tumour, cancer cells are embedded in stromal cells,
      namely cancer-associated fibroblasts (CAFs). These CAFs are now accepted as
      important players in cancer dynamics, being involved in tumour growth and
      progression. Although there are various reports on the interaction between tumour
      and stromal cells, the clinico-pathological significance of this cross-talk is
      still largely unknown. In this study, we aimed to characterise the expression of
      key metabolic proteins involved in glucose transport, pyruvate/lactate shuttle
      system, glycolytic metabolism and fatty acid oxidation in CAFs and tumour cells
      in different stages of malignant transformation. We further aimed to
      contextualise the clinico-pathological significance of these protein expression
      profiles with reference to known prognostic indicators, including biochemical
      recurrence in pT stage. METHODS: Prostate tissues were obtained from 480 patients
      with a median age of 64 years following radical prostatectomy with no previous
      hormonal therapy. Tissues were analysed for the expression of several key
      metabolism-related proteins in glands and surrounding fibroblasts by
      immunohistochemistry. Reliable markers of prognosis such as pT stage and
      biochemical recurrence were assessed for each case. RESULTS: We observed that
      prostate cancer cells did not rely mainly on glycolytic metabolism, while there
      was a high expression of MCT4 and CAIX - in CAFs. This corroborates the
      hypothesis of the "Reverse Warburg effect" in prostate cancer, in which
      fibroblasts are under oxidative stress and express CAIX, an established hypoxia
      marker. We found that alterations in the expression of metabolism-related
      proteins were already evident in the early stages of malignant transformation,
      suggesting the continuing alteration of CAFs from an early stage. Additionally,
      and for the first time, we show that cases showing high MCT4 expression in CAFs
      with concomitant strong MCT1 expression in prostate cancer (PCa) cells are
      associated with poor clinical outcome, namely pT3 stage of the tumour.
      CONCLUSIONS: In summary, this work demonstrates for the first time the clinico
      pathological significance of the lactate shuttle in prostate cancer. It also
      suggests that other alterations in CAFs may be useful prognostic factors, and
      further supports the use of MCT1/MCT4 as targets for PCa therapy.

PMID- 24886075
TI  - Primary extranodal NK/T cell lymphoma, nasal-type of uterus with adenomyosis: a
      case report.
AB  - Natural killer (NK)/T cell lymphoma of the female genital tract is extremely
      rare. We here report a case of 'nasal type' NK/T cell lymphoma arising in the
      uterus with adenomyosis in a 41-year-old woman with fever and hypogastralgia. The
      histologic analysis demonstrated a highly aggressive tumor with characteristic
      angiocentric/angiodestructive growth pattern and focal necrosis. The lymphoma
      cells displayed a CD3epsilon/CD56/TIA-1/granzyme-B/Perforin-positive and
      CD20/CD79a/CD4/CD8-negative immunophenotype and positive for Epstein-Barr virus
      by EBER in situ hybridization. Clinically, the disease was limited to the uterus
      at the initial diagnosis, but progressed rapidly. The patient died on day 54
      after hysterectomy, irrespective of intensive chemotherapy. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1323474831125945.

PMID- 24886077
TI  - Reconsidering nutrition science: critical reflection with a cultural lens.
AB  - BACKGROUND: European culture gave birth to modern science as a means to
      investigate and explain the natural world. The biomedical disciplines that have
      since emerged, including nutrition, presuppose a web of basic presuppositions,
      background assumptions and implicit cultural values that are often overlooked and
      escape peer review. These "hidden subjectivities" are widely taken-for-granted
      while exerting a powerful hold on the scope, direction and patterns of
      disciplinary thought. Nutrition science currently has no accepted means of
      collectively attending to hidden subjectivities embedded within its methods and
      practice. Here I propose that directing inquiry into these dimensions holds
      potential to advance our discipline. METHODS: This critically reflective approach
      emerged from critical theory and the practice of cross-cultural engagement (CCE).
      CCE deliberately seeks out and critically engages food and health understandings
      of non-European cultures. Its protocol includes cognitive frameshifting, a
      practice of temporarily stepping outside of habitual thought patterns and into a
      non-biomedical framework of background assumptions. A cultural lens metaphor
      derives from CCE practice and is forwarded here as a viable means for restoring
      critically reflective attention to hidden subjectivities while also inviting
      further CCE practice within the discipline. RESULTS: Critical reflection with a
      cultural lens allows cognitive attachments to materialism, reductionism,
      mechanistic thought, naive realism, control over nature and pervasive subject
      object dichotomies between mind and matter, scientist and nature, experience and
      reality, among many others to become more available for critical consideration.
      Culturally diverse food and health understandings otherwise dismissed as
      "unscientific" or held in abeyance gain value as alternative assumptive
      frameworks and cognitive models that can be temporarily inhabited for further
      intercultural reflection and insight. CONCLUSION: Critical reflection with a
      cultural lens allows reconsideration of nutrition science in light of its
      culturally specific origin and foundation. This perspective can advance the
      discipline in two ways. First, it extends skeptical inquiry into hidden
      subjectivities that are otherwise implicit and seldom given over to critical
      consideration. Second, it can broaden scholarly inquiry through deliberate
      attempts to cross cognitive boundaries and empathically inhabit different
      cognitive worlds. This developmental practice holds potential to both deepen and
      broaden disciplinary inquiry.

PMID- 24886076
TI  - Association between polymorphisms in the flanking region of the TAFI gene and
      atherosclerotic cerebral infarction in a Chinese population.
AB  - BACKGROUND: Atherosclerosis is the leading etiologic factor of Atherosclerotic
      Cerebral Infarction (ACI). Previous studies have shown that thrombin activatable
      fibrinolysis inhibitor (TAFI) may play an important role in the occurrence of
      acute cerebral infarction, and the levels of TAFI are affected by several single
      nucleotide polymorphisms (SNPs) located in the regulatory and coding regions of
      the gene encoding TAFI. The present study aimed to determine whether
      polymorphisms (TAFI -2345 2G/1G, -1690 A/G, -438 A/G, +1583 A/T) of the TAFI gene
      were associated with ACI in a Han Chinese population. METHODS: The variant
      genotypes were identified by restriction fragment length polymorphism (RFLP) and
      allele-specific polymerase chain reactions (AS-PCR) in 225 patients with ACI and
      184 age-matched healthy individuals. RESULTS: There was a significant difference
      in the genotype and allele frequencies of TAFI -2345 2G/1G and -1690 A/G
      polymorphisms between the ACI and control subjects. Further stratification
      analysis by gender revealed that the presence of the -438 AA genotype and the A
      allele conferred a higher risk of developing ACI in male patients (p < 0.05).
      Haplotype analysis demonstrated that four haplotypes of TAFI are significantly
      associated with ACI. CONCLUSIONS: Our study provides preliminary evidence that
      the TAFI -2345 2G/1G and -1690 A/G polymorphisms are associated with ACI
      susceptibility in a Han Chinese population.

PMID- 24886078
TI  - Intestinal permeability in children/adolescents with functional dyspepsia.
AB  - BACKGROUND: An altered intestinal mucosal barrier has been demonstrated in
      subsets of patients with IBS and FAP and may be an additional biological factor
      contributing to symptom generation in children with FD. The objective of this
      study was to determine if intestinal permeability is increased in
      children/adolescents with functional dyspepsia (FD) and whether intestinal
      permeability is correlated with mucosal inflammation and/or symptoms of anxiety
      or depression in this population. METHODS: A sugar absorption test was performed
      in 19 patients with FD and 19 controls. Anxiety and depression were assessed in
      both groups utilizing a standard questionnaire. In FD patients, duodenal mean and
      peak mast cell and eosinophil densities were determined. RESULTS: Intestinal
      permeability as measured by the sugar absorption test did not differ between
      children with FD and controls. In children with FD, there was no correlation
      between permeability and mast cell density, eosinophil density, anxiety scores,
      or depression scores, respectively. CONCLUSIONS: Pediatric FD does not appear to
      be associated with increased small bowel intestinal permeability, however, there
      are some limitations to the current study. TRIAL REGISTRATION:
      ClinicalTrials.gov; NCT00363597.

PMID- 24886079
TI  - Combined effect of teriparatide and low-intensity pulsed ultrasound for nonunion:
      a case report.
AB  - BACKGROUND: Low-intensity pulsed ultrasound is a pain-free therapy performed
      daily at home by the patient and has been shown to promote fracture healing.
      Teriparatide is a parathyroid hormone preparation that activates osteoblastic
      bone formation and is also reported to be effective in promoting bony union. CASE
      PRESENTATION: We report the case of a 56-year-old Japanese male with a femoral
      shaft fracture who underwent intramedullary osteosynthesis nailing initially. He
      had no radiologic or clinical sign of healing 3 months later and low-intensity
      pulsed ultrasound was initiated at that time. He was reassessed in another 3
      months, with evidence of mild bone consolidation but the fracture gap persisted.
      Subsequent treatment with human parathyroid hormone was initiated in combination
      with low-intensity pulsed ultrasound. Full fracture healing was present 6 months
      after beginning the combination low-intensity pulsed ultrasound and teriparatide.
      It is hypothesized that the potential additive effects of low-intensity pulsed
      ultrasound and teriparatide therapy ultimately triggered sufficient bone
      formation to support osseous union. CONCLUSION: The case reported herein is a
      femoral shaft atrophic nonunion in which traditional interventions failed.
      Successful fracture healing was finally achieved with low-intensity pulsed
      ultrasound and teriparatide therapy. This is the first reported case of
      diaphyseal nonunion with deterioration of bone quality in long bones resolved
      with teriparatide and low-intensity pulsed ultrasound.

PMID- 24886080
TI  - Functional identification of genes responsible for the biosynthesis of 1-methoxy
      indol-3-ylmethyl-glucosinolate in Brassica rapa ssp. chinensis.
AB  - BACKGROUND: Brassica vegetables contain a class of secondary metabolites, the
      glucosinolates (GS), whose specific degradation products determine the
      characteristic flavor and smell. While some of the respective degradation
      products of particular GS are recognized as health promoting substances for
      humans, recent studies also show evidence that namely the 1-methoxy-indol-3
      ylmethyl GS might be deleterious by forming characteristic DNA adducts.
      Therefore, a deeper knowledge of aspects involved in the biosynthesis of indole
      GS is crucial to design vegetables with an improved secondary metabolite profile.
      RESULTS: Initially the leafy Brassica vegetable pak choi (Brassica rapa ssp.
      chinensis) was established as suitable tool to elicit very high concentrations of
      1-methoxy-indol-3-ylmethyl GS by application of methyl jasmonate. Differentially
      expressed candidate genes were discovered in a comparative microarray analysis
      using the 2 * 104 K format Brassica Array and compared to available gene
      expression data from the Arabidopsis AtGenExpress effort. Arabidopsis knock out
      mutants of the respective candidate gene homologs were subjected to a
      comprehensive examination of their GS profiles and confirmed the exclusive
      involvement of polypeptide 4 of the cytochrome P450 monooxygenase subfamily
      CYP81F in 1-methoxy-indol-3-ylmethyl GS biosynthesis. Functional characterization
      of the two identified isoforms coding for CYP81F4 in the Brassica rapa genome was
      performed using expression analysis and heterologous complementation of the
      respective Arabidopsis mutant. CONCLUSIONS: Specific differences discovered in a
      comparative microarray and glucosinolate profiling analysis enables the
      functional attribution of Brassica rapa ssp. chinensis genes coding for
      polypeptide 4 of the cytochrome P450 monooxygenase subfamily CYP81F to their
      metabolic role in indole glucosinolate biosynthesis. These new identified
      Brassica genes will enable the development of genetic tools for breeding
      vegetables with improved GS composition in the near future.

PMID- 24886081
TI  - Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft
      survival.
AB  - BACKGROUND: Herbal medicines have unique odors, and the act of smelling may have
      modulatory effects on the immune system. We investigated the effect of olfactory
      exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune
      responses in a murine model of cardiac allograft transplantation. METHODS: Naive
      or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart
      and were exposed to the odor of TJ-23 until rejection. Some naive CBA recipients
      of an allograft were given olfactory exposure to Sairei-to (TJ-114),
      trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation
      lacking one component. Adoptive transfer studies were performed to determine
      whether regulatory cells were generated. RESULTS: Untreated CBA mice rejected
      their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed
      to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure
      to TJ-23 had significantly prolonged allograft survival, whereas those exposed to
      the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did
      not. Secondary allograft recipients that were given, at 30 days after
      transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from
      primary recipients exposed to the odor of TJ-23 had indefinitely prolonged
      allograft survival. CONCLUSIONS: Prolonged survival of cardiac allografts and
      generation of regulatory cells was associated with exposure to the odor of TJ-23
      in our model. The olfactory area of the brain may have a role in the modulation
      of immune responses.

PMID- 24886082
TI  - Metformin induces an intracellular reductive state that protects oesophageal
      squamous cell carcinoma cells against cisplatin but not copper
      bis(thiosemicarbazones).
AB  - BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) is a highly aggressive
      carcinoma with a poor survival rate. One of the most commonly used
      chemotherapeutic drugs, cisplatin, displays varied and often poor efficacy in
      vivo. Therefore, alternative, cost-effective and more efficacious treatments are
      required. Metformin has been previously shown to reduce proliferative rates in
      various carcinoma cell lines. We report for the first time, the effect of
      metformin on OSCC cell proliferation and show that it antagonises cisplatin
      induced but not copper-bis(thiosemicarbazone)-induced cytotoxicity in OSCC cells.
      METHODS: Cell proliferation and stage of the cell cycle were quantified by trypan
      blue counts and flow cytometry, respectively. All cytotoxicity measurements were
      made using the tetrazolium based MTT assay. Metabolic alterations to cells were
      determined as follows: glycolysis via a lactate dehydrogenase assay, reducing
      equivalents by MTT reduction and reduced intracellular thiols by monobromobimane
      thiol fluorescence, and glutathione depletion using buthionine sulfoximine.
      Inductively coupled plasma mass spectrometry was used to quantify cisplatin-DNA
      adduct formation. RESULTS: Metformin was found to reduce cell proliferation
      significantly in all OSCC cell lines, with an accumulation of cells in G0/G1
      phase of the cell cycle. However, metformin significantly protected OSCC cells
      against cisplatin toxicity. Our results indicate that a major mechanism of
      metformin-induced cisplatin resistance results from a significant increase in
      glycolysis, intracellular NAD(P)H levels with a concomitant increase in reduced
      intracellular thiols, leading to decreased cisplatin-DNA adduct formation. The
      glutathione synthesis inhibitor buthionine sulfoximine significantly ablated the
      protective effect of metformin. We subsequently show that the copper
      bis(thiosemicarbazones), Cu-ATSM and Cu-GTSM, which are trapped in cells under
      reducing conditions, cause significant OSCC cytotoxicity, both alone and in
      combination with metformin. CONCLUSIONS: This is the first study showing that
      metformin can be used to decrease cell proliferation in OSCC cells. However,
      metformin protects against cisplatin cytotoxicity by inducing a reducing
      intracellular environment leading to lower cisplatin-DNA adduct formation. As
      such, we advise that caution be used when administering cisplatin to diabetic
      patients treated with metformin. Furthermore, we propose a novel combination
      therapy approach for OSCC that utilises metformin with metformin-compatible
      cytotoxic agents, such as the copper-bis(thiosemicarbazones), Cu-ATSM and Cu
      GTSM.

PMID- 24886083
TI  - New bandwidth selection criterion for Kernel PCA: approach to dimensionality
      reduction and classification problems.
AB  - BACKGROUND: DNA microarrays are potentially powerful technology for improving
      diagnostic classification, treatment selection, and prognostic assessment. The
      use of this technology to predict cancer outcome has a history of almost a
      decade. Disease class predictors can be designed for known disease cases and
      provide diagnostic confirmation or clarify abnormal cases. The main input to this
      class predictors are high dimensional data with many variables and few
      observations. Dimensionality reduction of these features set significantly speeds
      up the prediction task. Feature selection and feature transformation methods are
      well known preprocessing steps in the field of bioinformatics. Several prediction
      tools are available based on these techniques. RESULTS: Studies show that a well
      tuned Kernel PCA (KPCA) is an efficient preprocessing step for dimensionality
      reduction, but the available bandwidth selection method for KPCA was
      computationally expensive. In this paper, we propose a new data-driven bandwidth
      selection criterion for KPCA, which is related to least squares cross-validation
      for kernel density estimation. We propose a new prediction model with a well
      tuned KPCA and Least Squares Support Vector Machine (LS-SVM). We estimate the
      accuracy of the newly proposed model based on 9 case studies. Then, we compare
      its performances (in terms of test set Area Under the ROC Curve (AUC) and
      computational time) with other well known techniques such as whole data set + LS
      SVM, PCA + LS-SVM, t-test + LS-SVM, Prediction Analysis of Microarrays (PAM) and
      Least Absolute Shrinkage and Selection Operator (Lasso). Finally, we assess the
      performance of the proposed strategy with an existing KPCA parameter tuning
      algorithm by means of two additional case studies. CONCLUSION: We propose,
      evaluate, and compare several mathematical/statistical techniques, which apply
      feature transformation/selection for subsequent classification, and consider its
      application in medical diagnostics. Both feature selection and feature
      transformation perform well on classification tasks. Due to the dynamic selection
      property of feature selection, it is hard to define significant features for the
      classifier, which predicts classes of future samples. Moreover, the proposed
      strategy enjoys a distinctive advantage with its relatively lesser time
      complexity.

PMID- 24886084
TI  - Deletions of the SACPD-C locus elevate seed stearic acid levels but also result
      in fatty acid and morphological alterations in nitrogen fixing nodules.
AB  - BACKGROUND: Soybean (Glycine max) seeds are the primary source of edible oil in
      the United States. Despite its widespread utility, soybean oil is oxidatively
      unstable. Until recently, the majority of soybean oil underwent chemical
      hydrogenation, a process which also generates trans fats. An alternative to
      chemical hydrogenation is genetic modification of seed oil through identification
      and introgression of mutant alleles. One target for improvement is the elevation
      of a saturated fat with no negative cardiovascular impacts, stearic acid, which
      typically constitutes a minute portion of seed oil (~3%). RESULTS: We examined
      radiation induced soybean mutants with moderately increased stearic acid (10-15%
      of seed oil, ~3-5 X the levels in wild-type soybean seeds) via comparative whole
      genome hybridization and genetic analysis. The deletion of one SACPD isoform
      encoding gene (SACPD-C) was perfectly correlated with moderate elevation of seed
      stearic acid content. However, SACPD-C deletion lines were also found to have
      altered nodule fatty acid composition and grossly altered morphology. Despite
      these defects, overall nodule accumulation and nitrogen fixation were unaffected,
      at least under laboratory conditions. CONCLUSIONS: Although no yield penalty has
      been reported for moderate elevated seed stearic acid content in soybean seeds,
      our results demonstrate that genetic alteration of seed traits can have
      unforeseen pleiotropic consequences. We have identified a role for fatty acid
      biosynthesis, and SACPD activity in particular, in the establishment and
      maintenance of symbiotic nitrogen fixation.

PMID- 24886085
TI  - Kinetic measurements of hand motor impairments after mild to moderate stroke
      using grip control tasks.
AB  - BACKGROUND: The aim of this study is to investigate quantitative outcome
      measurements of hand motor performance for subjects after mild to moderate stroke
      using grip control tasks and characterize abnormal flexion synergy of upper
      extremities after stroke. METHODS: A customized dynamometer with force sensors
      was used to measure grip force and calculate rotation torque during the sub
      maximal grip control tasks. The paretic and nonpartic sides of eleven subjects
      after stroke and the dominant sides of ten healthy persons were tested. Their
      maximal voluntary grip force was measured and used to set sub-maximal grip
      control tasks at three different target force levels. Force control ability was
      characterized by the maximal grip force, mean force percentage, coefficient of
      variation (CV), target deviation ratio (TDR), and rotation torque ratio (RTR).
      The motor impairments of subjects after stroke were also evaluated using the Fugl
      Meyer assessment for upper extremity (FMA-UE) and Wolf Motor Function Test
      (WMFT). RESULTS: Maximal grip force of the paretic side was significantly reduced
      as compared to the nonparetic side and the healthy group, while the difference of
      maximal grip force between the nonparetic side and the healthy group was not
      significant. TDR and RTR increased for all three groups with increasing target
      force level. There were significant differences of CV, TDR and RTR between the
      paretic side and the healthy group at all the force levels. CV, TDR and RTR
      showed significant negative correlations with FMA-UE and WMFT at 50% of maximum
      grip force. CONCLUSIONS: This study designed a customized dynamometer together
      with an innovative measurement, RTR, to investigate the hand motor performance of
      subjects after mild to moderate stroke during force control tasks. And stroke
      induced abnormal flexion synergy of wrist and finger muscles could be
      characterized by RTR. This study also identified a set of kinetic parameters
      which can be applied to quantitatively assess the hand motor function of subjects
      after mild to moderate stroke.

PMID- 24886087
TI  - A comparison of the characteristics of suicide attempters with and without
      psychiatric consultation before their suicidal behaviours: a cross-sectional
      study.
AB  - BACKGROUND: Because psychiatric disorders are risk factors for suicide,
      psychiatric consultation should be an essential element of suicide prevention
      among individuals with a high risk of suicide. The aim of the present study was
      to compare the characteristics of individuals who had or had not received
      psychiatric consultation before they attempted suicide in Japan. METHODS:
      Clinical records were used to identify 300 consecutive persons who were admitted
      to the hospital for attempting suicide between April 2006 and March 2013. We
      divided the patients into two groups. One group consisted of patients who
      consulted a psychiatrist before their suicidal behaviours (the consultation
      group), and the other group consisted of patients who had not consulted a
      psychiatrist before their suicidal behaviours (the non-consultation group). Group
      differences were analysed with respect to gender, age, method of suicide
      attempts, psychiatric diagnosis (ICD-10), and duration of hospitalisation in the
      emergency unit. RESULTS: Females tended to be over-represented in the
      consultation group (73.0%), and males tended to be over-represented in the non
      consultation group (59.8%). Poisoning by prescription drugs was used more
      frequently as a method of suicide in the consultation group than in the non
      consultation group. Neuroticism and related disorders were higher in the non
      consultation group (33.7%) than in the consultation group (18.9%). Mood disorders
      (32.6%) were nearly as common as neuroticism in the non-consultation group, and
      together they accounted for almost two-thirds of all diagnoses. Mood disorders
      were comparable between the consultation group (30.9%) and the non-consultation
      group (32.6%). Adult personality disorders (13.3%) and schizophrenia and related
      disorders (26.0%) were higher in the consultation group than in the non
      consultation group. CONCLUSIONS: Measures have to be taken to encourage people
      with these diverse characteristics to consult psychiatrists, and psychiatrists
      have to regularly evaluate patients for suicide risk. Furthermore, we need
      further research on the relationship between psychiatric consultation and
      poisoning by prescribed drugs.

PMID- 24886088
TI  - De novo assembly and transcriptome characterization: novel insights into the
      natural resistance mechanisms of Microtus fortis against Schistosoma japonicum.
AB  - BACKGROUND: Microtus fortis is a non-permissive host of Schistosoma japonicum. It
      has natural resistance against schistosomes, although the precise resistance
      mechanisms remain unclear. The paucity of genetic information for M. fortis
      limits the use of available immunological methods. Thus, studies based on high
      throughput sequencing technologies are required to obtain information about
      resistance mechanisms against S. japonicum. RESULTS: Using Illumina single-end
      technology, a de novo assembly of the M. fortis transcriptome produced 67,751
      unigenes with an average length of 868 nucleotides. Comparisons were made between
      M. fortis before and after infection with S. japonicum using RNA-seq
      quantification analysis. The highest number of differentially expressed genes
      (DEGs) occurred two weeks after infection, and the highest number of down
      regulated DEGs occurred three weeks after infection. Simultaneously, the
      strongest pathological changes in the liver were observed at week two. Gene
      ontology terms and pathways related to the DEGs revealed that up-regulated
      transcripts were involved in metabolism, immunity and inflammatory responses.
      Quantitative real-time PCR analysis showed that patterns of gene expression were
      consistent with RNA-seq results. CONCLUSIONS: After infection with S. japonicum,
      a defensive reaction in M. fortis commenced rapidly, increasing dramatically in
      the second week, and gradually decreasing three weeks after infection. The
      obtained M. fortis transcriptome and DEGs profile data demonstrated that natural
      and adaptive immune responses, play an important role in M. fortis immunity to S.
      japonicum. These findings provide a better understanding of the natural
      resistance mechanisms of M. fortis against schistosomes.

PMID- 24886090
TI  - Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31
      in patellar luxation in Flat-Coated Retrievers.
AB  - BACKGROUND: Patellar luxation is an orthopedic disorder in which the patella
      moves out of its normal location within the femoral trochlea of the knee and it
      can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait,
      with both environmental and genetic factors contributing to the phenotype. The
      prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is
      24%. In this study, we investigated the molecular genetics of the disorder in
      this population. RESULTS: Genome-wide association analysis of 15,823 single
      nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that
      patellar luxation was significantly associated with a region on chromosome CFA07,
      and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in
      these regions, 0.5 Mb combined, were analyzed further. These exons from 15 cases
      and a pooled sample from 15 controls were enriched using custom genomic
      hybridization arrays and analyzed by massive parallel DNA sequencing. In total
      7257 variations were detected. Subsequently, a selection of 144 of these SNPs
      were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07
      and CFA31, were associated with patellar luxation (P <10-4). Genotyping of these
      SNPs in samples from a variety of breeds revealed that the disease-associated
      allele of one synonymous SNP in a pseudogene of FMO6 was unique to Flat-Coated
      Retrievers. CONCLUSION: Genome-wide association analysis followed by targeted DNA
      sequencing identified loci on chromosomes 7 and 31 as being involved in patellar
      luxation in the Flat-Coated Retriever breed.

PMID- 24886089
TI  - DTX3L and ARTD9 inhibit IRF1 expression and mediate in cooperation with ARTD8
      survival and proliferation of metastatic prostate cancer cells.
AB  - BACKGROUND: Prostate cancer (PCa) is one of the leading causes of cancer-related
      mortality and morbidity in the aging male population and represents the most
      frequently diagnosed malignancy in men around the world. The Deltex (DTX)-3-like
      E3 ubiquitin ligase (DTX3L), also known as B-lymphoma and BAL-associated protein
      (BBAP), was originally identified as a binding partner of the diphtheria-toxin
      like macrodomain containing ADP-ribosyltransferase-9 (ARTD9), also known as BAL1
      and PARP9. We have previously demonstrated that ARTD9 acts as a novel oncogenic
      survival factor in high-risk, chemo-resistant, diffuse large B cell lymphoma
      (DLBCL). The mono-ADP-ribosyltransferase ARTD8, also known as PARP14 functions as
      a STAT6-specific co-regulator of IL4-mediated proliferation and survival in B
      cells. METHODS: Co-expression of DTX3L, ARTD8, ARTD9 and STAT1 was analyzed in
      the metastatic PCa (mPCa) cell lines PC3, DU145, LNCaP and in the normal prostate
      luminal epithelial cell lines HPE and RWPE1. Effects on cell proliferation,
      survival and cell migration were determined in PC3, DU145 and/or LNCaP cells
      depleted of DTX3L, ARTD8, ARTD9, STAT1 and/or IRF1 compared to their proficient
      control cells, respectively. In further experiments, real-time RT-PCR, Western
      blot, immunofluorescence and co-immunoprecipitations were conducted to evaluate
      the physical and functional interactions between DTX3L, ARTD8 and ARTD9. RESULTS:
      Here we could identify DTX3L, ARTD9 and ARTD8 as novel oncogenic survival factors
      in mPCa cells. Our studies revealed that DTX3L forms a complex with ARTD8 and
      mediates together with ARTD8 and ARTD9 proliferation, chemo-resistance and
      survival of mPCa cells. In addition, DTX3L, ARTD8 and ARTD9 form complexes with
      each other. Our study provides first evidence that the enzymatic activity of
      ARTD8 is required for survival of mPCa cells. DTX3L and ARTD9 act together as
      repressors of the tumor suppressor IRF1 in mPCa cells. Furthermore, the present
      study shows that DTX3L together with STAT1 and STAT3 is implicated in cell
      migration of mPCa cells. CONCLUSIONS: Our data strongly indicate that a crosstalk
      between STAT1, DTX3L and ARTD-like mono-ADP-ribosyltransferases mediates
      proliferation and survival of mPCa cells. The present study further suggests that
      the combined targeted inhibition of STAT1, ARTD8, ARTD9 and/or DTX3L could
      increase the efficacy of chemotherapy or radiation treatment in prostate and
      other high-risk tumor types with an increased STAT1 signaling.

PMID- 24886092
TI  - Measuring use of research evidence in public health policy: a policy content
      analysis.
AB  - BACKGROUND: There are few Australian studies showing how research evidence is
      used to inform the development of public health policy. International research
      has shown that compensation for injury rehabilitation can have negative impacts
      on health outcomes. This study examined transport injury compensation policy in
      the Australian state of Victoria to: determine type and purpose of reference to
      information sources; and to identify the extent of reference to academic research
      evidence in transport related injury rehabilitation compensation policy. METHODS:
      Quantitative content analysis of injury rehabilitation compensation policies (N =
      128) from the Victorian state government transport accident compensation
      authority. RESULTS: The most commonly referenced types of information were
      Internal Policy (median = 6 references per policy), Clinical/Medical (2.5), and
      Internal Legislation (1). Academic Research Evidence was the least often
      referenced source of information. The main purpose of reference to information
      was to support injury treatment and rehabilitation compensation claims decision
      making. CONCLUSIONS: Transport injury compensation policy development is complex;
      with multiple sources of information cited including legislation, internal
      policy, external policy and clinical/medical evidence. There is limited use of
      academic research evidence in Victorian state government injury treatment and
      rehabilitation compensation policies. Decisions regarding compensation for injury
      treatment and rehabilitation services could benefit from greater use of academic
      research evidence. This study is one of the first to examine the use of research
      evidence in existing Australian public health policy decision-making using
      rigorous quantitative methods. It provides a practical example of how use of
      research evidence in public health policy can be objectively measured.

PMID- 24886091
TI  - TGF-beta stimulation in human and murine cells reveals commonly affected
      biological processes and pathways at transcription level.
AB  - BACKGROUND: The TGF-beta signaling pathway is a fundamental pathway in the living
      cell, which plays a key role in many central cellular processes. The complex and
      sometimes contradicting mechanisms by which TGF-beta yields phenotypic effects
      are not yet completely understood. In this study we investigated and compared the
      transcriptional response profile of TGF-beta1 stimulation in different cell
      types. For this purpose, extensive experiments are performed and time-course
      microarray data are generated in human and mouse parenchymal liver cells, human
      mesenchymal stromal cells and mouse hematopoietic progenitor cells at different
      time points. We applied a panel of bioinformatics methods on our data to uncover
      common patterns in the dynamic gene expression response in respective cells.
      RESULTS: Our analysis revealed a quite variable and multifaceted transcriptional
      response profile of TGF-beta1 stimulation, which goes far beyond the well
      characterized classical TGF-beta1 signaling pathway. Nonetheless, we could
      identify several commonly affected processes and signaling pathways across cell
      types and species. In addition our analysis suggested an important role of the
      transcription factor EGR1, which appeared to have a conserved influence across
      cell-types and species. Validation via an independent dataset on A549 lung
      adenocarcinoma cells largely confirmed our findings. Network analysis suggested
      explanations, how TGF-beta1 stimulation could lead to the observed effects.
      CONCLUSIONS: The analysis of dynamical transcriptional response to TGF-beta
      treatment experiments in different human and murine cell systems revealed
      commonly affected biological processes and pathways, which could be linked to TGF
      beta1 via network analysis. This helps to gain insights about TGF-beta pathway
      activities in these cell systems and its conserved interactions between the
      species and tissue types.

PMID- 24886093
TI  - Sexual health is dead in my body: participatory assessment of sexual health
      determinants by refugees, asylum seekers and undocumented migrants in Belgium and
      The Netherlands.
AB  - BACKGROUND: Although migrants constitute an important proportion of the European
      population, little is known about migrant sexual health. Existing research mainly
      focuses on migrants' sexual health risks and accessibility issues while
      recommendations on adequate sexual health promotion are rarely provided. Hence,
      this paper explores how refugees, asylum seekers and undocumented migrants in
      Belgium and The Netherlands define sexual health, search for sexual health
      information and perceive sexual health determinants. METHODS: Applying Community
      based Participatory Research as the overarching research approach, we conducted
      223 in-depth interviews with refugees, asylum seekers and undocumented migrants
      in Belgium and The Netherlands. The Framework Analysis Technique was used to
      analyse qualitative data. We checked the extensiveness of the qualitative data
      and analysed the quantitative socio-demographic data with SPSS. RESULTS: Our
      results indicate that gender and age do not appear to be decisive determinants.
      However, incorporated cultural norms and education attainment are important to
      consider in desirable sexual health promotion in refugees, asylum seekers and
      undocumented migrants in Belgium and The Netherlands. Furthermore, our results
      demonstrate that these migrants have a predominant internal health locus of
      control. Yet, most of them feel that this personal attitude is hugely challenged
      by the Belgian and Dutch asylum system and migration laws which force them into a
      structural dependent situation inducing sexual ill-health. CONCLUSION: Refugees,
      asylum seekers and undocumented migrants in Belgium and The Netherlands are at
      risk of sexual ill-health. Incorporated cultural norms and attained education are
      important determinants to address in desirable sexual health promotion. Yet, as
      their legal status demonstrates to be the key determinant, the prime concern is
      to alter organizational and societal factors linked to the Belgian and Dutch
      asylum system. Refugees, asylum seekers and undocumented migrants in Belgium and
      The Netherlands should be granted the same opportunity as Belgian and Dutch
      citizens have, to become equally in control of their sexual health and sexuality.

PMID- 24886094
TI  - Food and beverage portion sizes in Australian children: a secondary analysis of
      1995 and 2007 national data.
AB  - BACKGROUND: Portion size of foods is reported to contribute to the rise in
      obesity prevalence. However, evidence of changes in portion size for commonly
      consumed foods in Australia is lacking. The aim was to evaluate whether
      Australian child and adolescent portion sizes of selected foods changed from 1995
      to 2007. METHODS: Time-series study, comparing dietary data from two national
      cross-sectional surveys in nationally representative population survey of
      Australian households. The dietary data was from children aged 2-16 years who
      participated in the 1995 National Nutrition Survey (n = 2198) and 2007 Australian
      National Children's Nutrition and Physical Activity Survey (n = 4799). RESULTS:
      Differences were found across survey years in median portion size of common foods
      and beverages assessed by 24-hour recalls for age and sex categories. Of the 61
      foods items evaluated across the whole population sample, portion size increased
      in 18 items, decreased in 22, with no change in 20, although the magnitude of
      change varied by age and sex. Decreases in portion size were detected for most
      dairy products, breakfast cereal, some packaged snack foods and vegetables, p <
      0.0001. Increases were detected for cooked chicken, mixed chicken dishes, bacon
      and ham (p < 0.0001), cooked meat (p < 0.05), fish (p < 0.01) and pizza (p <
      0.0001). No significant changes were detected for many items including white and
      wholemeal bread, mincemeat, chocolate and soft drink. CONCLUSIONS: Small changes
      in portion sizes were detected over 12 years in Australian children and
      adolescents with the degree of change varying by sex, age and food group.
      Knowledge of usual portion sizes could inform programs targeting appropriate
      serving sizes selection in children and adolescents.

PMID- 24886095
TI  - 'South Asian cocktail'--the concurrent use of opioids, benzodiazepines and
      antihistamines among injecting drug users in Nepal and associations with HIV risk
      behaviour.
AB  - BACKGROUND: Data of the Central Bureau of Statistic of Nepal from 2008 show a
      total of more than 46,000 illegal drug users, out of which 61% are injecting drug
      users (IDU). An injecting mix of medicines like opioids, benzodiazepines and
      antihistamines (the so-called South Asian cocktail) was prevalent. Furthermore,
      it is estimated that about 70,000 people are living with human immunodeficiency
      virus (HIV). The government of Nepal has started realizing and recognizing drug
      use and HIV as significant health and social issues. Harm reduction programs such
      as needle syringe exchange and opioid substitution treatment are being
      implemented. METHODS: The aim of this study is to obtain specific knowledge on
      the drug use behaviour and the health status of drug users with a focus on HIV in
      drug users with concurrent injection of opioids, benzodiazepines and
      antihistamines. After an initial mapping of Kathmandu Valley, 300 drug users in
      contact with different treatment and counselling centres were randomly chosen for
      the interviews. The research questionnaire was designed according to the European
      Addiction Severity Index (EuropASI) and Maudsley Addiction Profile standards.
      RESULTS: Ninety-one percent of the respondents are male and 9% female. Mean age
      is 28.7 years. Ninety-five percent are injecting drug users with a mean of 8.7
      years of drug use history. Eighty-six percent are injecting different
      'cocktails', usually made of buprenorphine, diazepam, promethazine and/or other
      substances (30-day prevalence). Similarly, 48% use heroin, whereas only 2% take
      cocaine/crack. Among those tested for HIV (N = 223), 33% are positive (25% of the
      sample population). Compared to the other drug users (mainly heroin), the
      cocktail users show a higher HIV infection rate and more co-infections.
      Furthermore, risk behaviour, as e.g. needle sharing, is much more common among
      the cocktail users. CONCLUSION: Currently, the mixture of medicines, opioids,
      benzodiazepines and antihistamines, is the predominant drug in Nepal; the
      pharmaceutical drugs needed to prepare the cocktail are less expensive than
      heroin and relatively easy to acquire. The cocktail users show a higher risk
      behaviour regarding the transmission of HIV than heroin drug users. It needs to
      be considered which HIV prevention measures are necessary to target the specific
      needs of drug users who inject a mixture of opioids, benzodiazepines and
      antihistamines, since the available services (such as needle syringe exchange) do
      not seem to cover their specific needs (high percentage of needle sharing).

PMID- 24886096
TI  - Novel wireless electroencephalography system with a minimal preparation time for
      use in emergencies and prehospital care.
AB  - BACKGROUND: Although clinical applications such as emergency medicine and
      prehospital care could benefit from a fast-mounting electroencephalography (EEG)
      recording system, the lack of specifically designed equipment restricts the use
      of EEG in these environments. METHODS: This paper describes the design and
      testing of a six-channel emergency EEG (emEEG) system with a rapid preparation
      time intended for use in emergency medicine and prehospital care. The novel
      system comprises a quick-application cap, a device for recording and transmitting
      the EEG wirelessly to a computer, and custom software for displaying and
      streaming the data in real-time to a hospital. Bench testing was conducted, as
      well as healthy volunteer and patient measurements in three different
      environments: a hospital EEG laboratory, an intensive care unit, and an
      ambulance. The EEG data was evaluated by two experienced clinical
      neurophysiologists and compared with recordings from a commercial system.
      RESULTS: The bench tests demonstrated that the emEEG system's performance is
      comparable to that of a commercial system while the healthy volunteer and patient
      measurements confirmed that the system can be applied quickly and that it records
      quality EEG data in a variety of environments. Furthermore, the recorded data was
      judged to be of diagnostic quality by two experienced clinical
      neurophysiologists. CONCLUSIONS: In the future, the emEEG system may be used to
      record high-quality EEG data in emergency medicine and during ambulance
      transportation. Its use could lead to a faster diagnostic, a more accurate
      treatment, and a shorter recovery time for patients with neurological brain
      disorders.

PMID- 24886097
TI  - Entrapment of an EGFR inhibitor into nanostructured lipid carriers (NLC) improves
      its antitumor activity against human hepatocarcinoma cells.
AB  - BACKGROUND: In hepatocellular carcinoma (HCC), different signaling pathways are
      de-regulated, and among them, the expression of the epidermal growth factor
      receptor (EGFR). Tyrphostin AG-1478 is a lipophilic low molecular weight
      inhibitor of EGFR, preferentially acting on liver tumor cells. In order to
      overcome its poor drug solubility and thus improving its anticancer activity, it
      was entrapped into nanostructured lipid carriers (NLC) by using safe ingredients
      for parenteral delivery. RESULTS: Nanostructured lipid carriers (NLC) carrying
      tyrphostin AG-1478 were prepared by using the nanoprecipitation method and
      different matrix compositions. The best system in terms of mean size, PDI, zeta
      potential, drug loading and release profile was chosen to evaluate the anti
      proliferative effect of drug-loaded NLC versus free drug on human hepatocellular
      carcinoma HA22T/VGH cells. CONCLUSIONS: Thanks to the entrapment into NLC
      systems, tyrphostin AG-1478 shows an enhanced in vitro anti-tumor activity
      compared to free drug. These finding raises hope of future drug delivery strategy
      of tyrphostin AG-1478 -loaded NLC targeted to the liver for the HCC treatment.

PMID- 24886098
TI  - A randomised controlled trial of extended immersion in multi-method continuing
      simulation to prepare senior medical students for practice as junior doctors.
AB  - BACKGROUND: Many commencing junior doctors worldwide feel ill-prepared to deal
      with their new responsibilities, particularly prescribing. Simulation has been
      widely utilised in medical education, but the use of extended multi-method
      simulation to emulate the junior doctor experience has rarely been reported.
      METHODS: A randomised controlled trial compared students who underwent two, week
      long, extended simulations, several months apart (Intervention), with students
      who attended related workshops and seminars alone (Control), for a range of
      outcome measures. RESULTS: Eighty-four third year students in a graduate-entry
      medical program were randomised, and 82 completed the study. At the end of the
      first week, Intervention students scored a mean of 75% on a prescribing test,
      compared with 70% for Control students (P = 0.02) and Intervention teams
      initiated cardiac compressions a mean of 29.1 seconds into a resuscitation test
      scenario, compared with 70.1 seconds for Control teams (P < 0.01). At the
      beginning of the second week, an average of nine months later, a significant
      difference was maintained in relation to the prescribing test only (78% vs 70%, P
      < 0.01).At the end of the second week, significant Intervention vs Control
      differences were seen on knowledge and reasoning tests, a further prescribing
      test (71% vs 63% [P < 0.01]) and a paediatric resuscitation scenario test (252
      seconds to initiation of fluid resuscitation vs 339 seconds [P = 0.05]).
      CONCLUSIONS: The study demonstrated long-term retention of improved prescribing
      skills, and an immediate effect on knowledge acquisition, reasoning and
      resuscitation skills, from contextualising learning activities through extended
      multi-method simulation.

PMID- 24886099
TI  - Quantitative trait loci analysis of fiber quality traits using a random-mated
      recombinant inbred population in Upland cotton (Gossypium hirsutum L.).
AB  - BACKGROUND: Upland cotton (Gossypium hirsutum L.) accounts for about 95% of world
      cotton production. Improving Upland cotton cultivars has been the focus of world
      wide cotton breeding programs. Negative correlation between yield and fiber
      quality is an obstacle for cotton improvement. Random-mating provides a potential
      methodology to break this correlation. The suite of fiber quality traits that
      affect the yarn quality includes the length, strength, maturity, fineness,
      elongation, uniformity and color. Identification of stable fiber quantitative
      trait loci (QTL) in Upland cotton is essential in order to improve cotton
      cultivars with superior quality using marker-assisted selection (MAS) strategy.
      RESULTS: Using 11 diverse Upland cotton cultivars as parents, a random-mated
      recombinant inbred (RI) population consisting of 550 RI lines was developed after
      6 cycles of random-mating and 6 generations of self-pollination. The 550 RILs
      were planted in triplicates for two years in Mississippi State, MS, USA to obtain
      fiber quality data. After screening 15538 simple sequence repeat (SSR) markers,
      2132 were polymorphic among the 11 parents. One thousand five hundred eighty-two
      markers covering 83% of cotton genome were used to genotype 275 RILs (Set 1). The
      marker-trait associations were analyzed using the software program TASSEL. At p <
      0.01, 131 fiber QTLs and 37 QTL clusters were identified. These QTLs were
      responsible for the combined phenotypic variance ranging from 62.3% for short
      fiber content to 82.8% for elongation. The other 275 RILs (Set 2) were analyzed
      using a subset of 270 SSR markers, and the QTLs were confirmed. Two major QTL
      clusters were observed on chromosomes 7 and 16. Comparison of these 131 QTLs with
      the previously published QTLs indicated that 77 were identified before, and 54
      appeared novel. CONCLUSIONS: The 11 parents used in this study represent a
      diverse genetic pool of the US cultivated cotton, and 10 of them were elite
      commercial cultivars. The fiber QTLs, especially QTL clusters reported herein can
      be readily implemented in a cotton breeding program to improve fiber quality via
      MAS strategy. The consensus QTL regions warrant further investigation to better
      understand the genetics and molecular mechanisms underlying fiber development.

PMID- 24886100
TI  - Production and early preservation of lipid biomarkers in iron hot springs.
AB  - The bicarbonate-buffered anoxic vent waters at Chocolate Pots hot springs in
      Yellowstone National Park are 51-54 degrees C, pH 5.5-6.0, and are very high in
      dissolved Fe(II) at 5.8-5.9 mg/L. The aqueous Fe(II) is oxidized by a combination
      of biotic and abiotic mechanisms and precipitated as primary siliceous nanophase
      iron oxyhydroxides (ferrihydrite). Four distinct prokaryotic photosynthetic
      microbial mat types grow on top of these iron deposits. Lipids were used to
      characterize the community composition of the microbial mats, link source
      organisms to geologically significant biomarkers, and investigate how iron
      mineralization degrades the lipid signature of the community. The phospholipid
      and glycolipid fatty acid profiles of the highest-temperature mats indicate that
      they are dominated by cyanobacteria and green nonsulfur filamentous anoxygenic
      phototrophs (FAPs). Diagnostic lipid biomarkers of the cyanobacteria include
      midchain branched mono- and dimethylalkanes and, most notably, 2
      methylbacteriohopanepolyol. Diagnostic lipid biomarkers of the FAPs (Chloroflexus
      and Roseiflexus spp.) include wax esters and a long-chain tri-unsaturated alkene.
      Surprisingly, the lipid biomarkers resisted the earliest stages of microbial
      degradation and diagenesis to survive in the iron oxides beneath the mats.
      Understanding the potential of particular sedimentary environments to capture and
      preserve fossil biosignatures is of vital importance in the selection of the best
      landing sites for future astrobiological missions to Mars. This study explores
      the nature of organic degradation processes in moderately thermal Fe(II)-rich
      groundwater springs--environmental conditions that have been previously
      identified as highly relevant for Mars exploration.

PMID- 24886101
TI  - WHO multicentre study for the development of growth standards from fetal life to
      childhood: the fetal component.
AB  - BACKGROUND: In 2006 WHO presented the infant and child growth charts suggested
      for universal application. However, major determinants for perinatal outcomes and
      postnatal growth are laid down during antenatal development. Accordingly,
      monitoring fetal growth in utero by ultrasonography is important both for
      clinical and scientific reasons. The currently used fetal growth references are
      derived mainly from North American and European population and may be
      inappropriate for international use, given possible variances in the growth rates
      of fetuses from different ethnic population groups. WHO has, therefore, made it a
      high priority to establish charts of optimal fetal growth that can be recommended
      worldwide. METHODS: This is a multi-national study for the development of fetal
      growth standards for international application by assessing fetal growth in
      populations of different ethnic and geographic backgrounds. The study will select
      pregnant women of high-middle socioeconomic status with no obvious environmental
      constraints on growth (adequate nutritional status, non-smoking), and normal
      pregnancy history with no complications likely to affect fetal growth. The study
      will be conducted in centres from ten developing and industrialized countries:
      Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany,
      India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited
      between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal
      biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week)
      to be performed by trained ultrasonographers.The main outcome of the proposed
      study will be the development of fetal growth standards (either global or
      population specific) for international applications. DISCUSSION: The data from
      this study will be incorporated into obstetric practice and national health
      policies at country level in coordination with the activities presently conducted
      by WHO to implement the use of the Child Growth Standards.

PMID- 24886102
TI  - The World Health Organization Quality of Life instrument for people with
      intellectual and physical disabilities (WHOQOL-Dis): evidence of validity of the
      Brazilian version.
AB  - BACKGROUND: The number of people with disabilities in Brazil and worldwide has
      grown substantially in recent decades. Cross-cultural quality of life instruments
      can be helpful in the development of interventions designed to meet the needs of
      this population and contribute to rational allocation of resources. This study
      sought to provide evidence of validity and reliability the Brazilian Portuguese
      version of WHOQOL-Dis-D (a cross-cultural, multicentre instrument developed by
      the WHOQOL-Group for the assessment of quality of life in persons with physical
      disability - PD) and WHOQOL-Dis-ID (for persons with intellectual disability -
      ID). METHODS: Classical psychometric methods were used to conduct independent
      analyses of the PD and ID samples. Criterion groups were established for analysis
      of construct validity. Concurrent validity was assessed in relation to SWLS and
      BDI-II scores; discriminant validity, in relation to WHODAS-II. Cronbach alpha
      was used to test the instrument scales and subscales for reliability. The ID
      subgroup was retested, and test-retest reliability assessed by means of
      intraclass correlation coefficients and paired Student's t-test. RESULTS: A total
      of 162 (98 females) people with PD and 156 (55 females) people with ID
      participated in the study. Cronbach alpha was satisfactory across practically all
      domains and factors in the PD subsample. In IDs, most factors or domains had
      coefficients higher than 0.70, but four subscales exhibited less satisfactory
      performance. Evidence of construct and concurrent validity and reliability were
      obtained. CONCLUSIONS: The analyses presented herein provide satisfactory
      evidence of the validity and reliability of the instrument and corroborated the
      factor structure revealed during cross-cultural research. Further studies with
      larger sample sizes are required to obtain additional evidence of validity and
      reliability.

PMID- 24886104
TI  - Bronchial epithelial cells are rendered insensitive to glucocorticoid
      transactivation by transforming growth factor-beta1.
AB  - BACKGROUND: We have previously shown that transforming growth factor-beta (TGF
      beta) impairs glucocorticoid (GC) function in pulmonary epithelial cell-lines.
      However, the signalling cascade leading to this impairment is unknown. In the
      present study, we provide the first evidence that TGF-beta impairs GC action in
      differentiated primary air-liquid interface (ALI) human bronchial epithelial
      cells (HBECs). Using the BEAS-2B bronchial epithelial cell line, we also present
      a systematic examination of the known pathways activated by TGF-beta, in order to
      ascertain the molecular mechanism through which TGF-beta impairs epithelial GC
      action. METHODS: GC transactivation was measured using a Glucocorticoid Response
      Element (GRE)-Secreted embryonic alkaline phosphatase (SEAP) reporter and
      measuring GC-inducible gene expression by qRT-PCR. GC transrepression was
      measured by examining GC regulation of pro-inflammatory mediators. TGF-beta
      signalling pathways were investigated using siRNA and small molecule kinase
      inhibitors. GRalpha level, phosphorylation and sub-cellular localisation were
      determined by western blotting, immunocytochemistry and localisation of GRalpha
      Yellow Fluorescent Protein (YFP). Data are presented as the mean +/- SEM for n
      independent experiments in cell lines, or for experiments on primary HBEC cells
      from n individual donors. All data were statistically analysed using GraphPad
      Prism 5.0 (Graphpad, San Diego, CA). In most cases, two-way analyses of variance
      (ANOVA) with Bonferroni post-hoc tests were used to analyse the data. In all
      cases, P <0.05 was considered to be statistically significant. RESULTS: TGF-beta
      impaired Glucocorticoid Response Element (GRE) activation and the GC induction of
      several anti-inflammatory genes, but did not broadly impair the regulation of pro
      inflammatory gene expression in A549 and BEAS-2B cell lines. TGF-beta-impairment
      of GC transactivation was also observed in differentiated primary HBECs. The TGF
      beta receptor (ALK5) inhibitor SB431541 fully prevented the GC transactivation
      impairment in the BEAS-2B cell line. However, neither inhibitors of the known
      downstream non-canonical signalling pathways, nor knocking down Smad4 by siRNA
      prevented the TGF-beta impairment of GC activity. CONCLUSIONS: Our results
      indicate that TGF-beta profoundly impairs GC transactivation in bronchial
      epithelial cells through activating ALK5, but not through known non-canonical
      pathways, nor through Smad4-dependent signalling, suggesting that TGF-beta may
      impair GC action through a novel non-canonical signalling mechanism.

PMID- 24886103
TI  - Identification and genotyping of feline infectious peritonitis-associated single
      nucleotide polymorphisms in the feline interferon-gamma gene.
AB  - Feline infectious peritonitis (FIP) is an immune-mediated, highly lethal disease
      caused by feline coronavirus (FCoV) infection. Currently, no protective vaccine
      or effective treatment for the disease is available. Studies have found that some
      cats survive the challenge of virulent FCoV isolates. Since cellular immunity is
      thought to be critical in preventing FIP and because diseased cats often show a
      significant decrease in interferon-gamma (IFN-gamma) production, we investigated
      whether single nucleotide polymorphisms (SNP) in the feline IFN-gamma gene
      (fIFNG) are associated with the outcome of infection. A total of 82 asymptomatic
      and 63 FIP cats were analyzed, and 16 SNP were identified in intron 1 of fIFNG.
      Among these SNP, the fFING + 428 T allele was shown to be a FIP-resistant allele
      (p = 0.03), and the heterozygous genotypes 01C/T and +408C/T were found to be FIP
      susceptible factors (p = 0.004). Furthermore, an fIFNG + 428 resistant allele
      also showed a clear correlation with the plasma level of IFN-gamma in FIP cats.
      For the identification of these three FIP-related SNP, genotyping methods were
      established using amplification refractory mutation system PCR (ARMS-PCR) and
      restriction fragment length polymorphisms (RFLP), and the different genotypes
      could easily be identified without sequencing. The identification of additional
      FIP-related SNP will allow the selection of resistant cats and decrease the
      morbidity of the cat population to FIP.

PMID- 24886105
TI  - Migration background is associated with caries in Viennese school children, even
      if parents have received a higher education.
AB  - BACKGROUND: A low level of education and the migration background of parents are
      associated with the development of caries in children. The aim of this study was
      to evaluate whether a higher educational level of parents can overcome risks for
      the development of caries in immigrants in Vienna, Austria. METHODS: The
      educational level of the parents, the school type, and the caries status of 736
      randomly selected twelve-year-old children with and without migration background
      was determined in this cross sectional study. In children attending school in
      Vienna the decayed, missing, and filled teeth (DMFT) index was determined. For
      statistical analysis, a mixed negative-binomial-model was used. RESULTS: The
      caries status of the children with migration background was significantly worse
      compared to that of the native Viennese population. A significant interaction was
      found between migration background and the educational level of the parents (p =
      0.045). No interaction was found between the school type and either the migration
      background (p = 0.220) or the education level of the parents (p = 0.08). In
      parents with a higher scholarly education level, migration background (p < 0.01)
      and school type (p = 0.018) showed an association with DMFT values. In parents
      with a low education level, however, migration background and school type had no
      significant association with DMFT values. CONCLUSION: These data indicate that
      children with a migration background are at higher risk to acquire caries than
      other Viennese children, even when the parents have received a higher education.

PMID- 24886106
TI  - Influence of a family history of type 2 diabetes, demographic and clinical data
      on carotid intima-media thickness in patients with type 1 diabetes: a cross
      sectional study.
AB  - BACKGROUND: Intima-media thickness (IMT) of the common carotid artery is a
      surrogate end point of cardiovascular disease (CVD). Identifying the factors
      associated with a higher IMT may contribute to the identification of subjects
      with higher CVD risk. Our objective was to compare the common carotid IMT of type
      1 diabetes patients to healthy control subjects. The secondary objective was to
      determine factors associated with a higher carotid IMT. METHODS: We conducted a
      cross-sectional study between March 2009 and October 2013, comprising 127 type 1
      diabetes patients and 125 control subjects matched by age, gender and body mass
      index (BMI). Carotid IMT was measured using semi-automated edge detection
      software. RESULTS: Type 1 diabetes patients had a higher median IMT compared with
      control subjects (0.538; IQR: 0.500-0.607 vs 0.513 mm; IQR: 0.481-0.557,
      respectively p = 0.001). Women with type 1 diabetes had a higher median IMT
      difference compared to the control group (0.537; IQR: 0.495-0.596 vs 0.502 mm;
      IQR: 0.472-0.543, respectively p = 0.003) than did men with type 1 diabetes
      (0.547; IQR: 0.504-0.613 vs 0.528 mm; IQR: 0.492-0.575, respectively p = 0.2).
      Age and diabetes duration had an additive effect on the IMT of type 1 diabetes
      patients. Multivariate gamma regression model analysis showed that in type 1
      diabetes patients, the IMT was associated with age (Exp (beta) = 1.006, p <
      0.001), duration of diabetes (Exp (beta) = 1.004, p = 0.001), BMI (Exp (beta) =
      1.005, p = 0.021), family history of type 2 diabetes (Exp (beta) = 1.044, p =
      0.033), total cholesterol (Exp (beta) = 0.999, p = 0.001) and creatinine
      clearance (Exp (beta) = 1.000, p = 0.043). CONCLUSIONS: Patients with type 1
      diabetes have increased IMT, a marker of subclinical atherosclerosis. The CVD
      risk may be similar between men and women with type 1 diabetes, suggesting a loss
      of gender protection. Also, CVD risk may be higher in those with a family history
      of type 2 diabetes. Prospective studies are needed to confirm the predictive
      value of these findings and the causal effect between IMT and CVD in patients
      with type 1 diabetes.

PMID- 24886108
TI  - Enhanced crystallization rate of poly(L-lactic acid) (PLLA) by polyoxymethylene
      (POM) fragment crystals in the PLLA/POM blends with a small amount of POM.
AB  - Phase diagrams and glass transition behaviors of poly(L-lactic
      acid)/polyoxymethylene (PLLA/POM) blends have been investigated in our previous
      work (Macromolecules 2013, 46, 5806-5814). In this work, the crystallization
      behaviors and physical properties of the PLLA/POM blends with the PLLA as the
      major component have been systematically studied. POM was crystallized into the
      fragment crystals that were finely dispersed in the PLLA matrix when cooling down
      from the melt of the blends. It was found that the POM fragment crystals
      accelerated the crystallization process of PLLA matrix and increased the final
      crystallinity of PLLA significantly in the blends. At the same time, the PLLA
      spherulites nucleated by POM fragment crystals were much smaller than those
      obtained from neat PLLA. It was further found that the crystallization rate of
      PLLA was quite dependent upon the POM loadings and the highest crystallization
      rate was observed at POM loadings of 7 wt %. It is considered that the POM
      fragment crystals take the nuclei role to initiate the crystallization of PLLA at
      low POM loadings, while a high content of POM in the blends leads to the large
      POM spherulites that cannot nucleate PLLA crystallization effectively. The
      obtained PLLA/POM blends at low POM loadings with small PLLA spherulites
      exhibited excellent optical transmittance and good mechanical performance.

PMID- 24886107
TI  - PAHA study: psychological active and healthy aging: psychological wellbeing,
      proactive attitude and happiness effects of whole-body vibration versus
      Multicomponent Training in aged women: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Evidence demonstrates that physical exercise and psychological
      wellbeing are closely interlinked, particularly in older-aged women. However,
      research investigating how different forms of exercise influence mental health in
      older-aged women is underdeveloped. METHODS/DESIGN: A randomized controlled trial
      (N = 300) will assess the relative effectiveness of two different exercise
      programs (whole-body vibration and Multicomponent Training) for improving
      psychological wellbeing in older-aged women. The following outcomes will be
      assessed at three time points (that is, pre, post, and follow-up): psychological
      wellbeing, proactive attitude, quality of life, and happiness. DISCUSSION:
      Results will have important implications for preventing psychological and
      physiological disease in older-aged women and for managing health-related costs
      for this population group. TRIAL REGISTRATION: Number NCT01966562 on Clinical Gov
      database the 8 October 2013.

PMID- 24886110
TI  - Economics of chronic diseases protocol: cost-effectiveness modelling and the
      future burden of non-communicable disease in Europe.
AB  - BACKGROUND: The majority of chronic disease is caused by risk factors which are
      mostly preventable. Effective interventions to reduce these risks are known and
      proven to be applicable to a variety of settings. Chronic disease is generally
      developed long before the fatal outcome, meaning that a lot of people spend a
      number of years in poor health. Effective prevention measures can prolong lives
      of individuals and significantly improve their quality of life. However, the
      methods to measure cost-effectiveness are a subject to much debate. The Economics
      of Chronic Diseases project aims to establish the best possible methods of
      measuring cost-effectiveness as well as develop micro-simulation models apt at
      projecting future burden of chronic diseases, their costs and potential savings
      after implementation of cost-effective interventions. METHOD: This research
      project will involve eight European countries: Bulgaria, Finland, Greece,
      Lithuania, The Netherlands, Poland, Portugal and the United Kingdom (UK). A
      literature review will be conducted to identify scientific articles which
      critically review the methods of cost-effectiveness. Contact will be made health
      economists to inform and enrich this review. This evidence will be used as a
      springboard for discussion at a meeting with key European stakeholders and
      experts with the aim of reaching a consensus on recommendations for cost
      effectiveness methodology. Epidemiological data for coronary heart disease,
      chronic kidney disease, type 2 diabetes and chronic obstructive pulmonary disease
      will be collected along with data on time trends in three major risk factors
      related to these diseases, specifically tobacco consumption, blood pressure and
      body mass index. Economic and epidemiological micro-simulation models will be
      developed to asses the future distributions of risks, disease outcomes,
      healthcare costs and the cost-effectiveness of interventions to reduce the burden
      of chronic diseases in Europe. DISCUSSION: This work will help to establish the
      best methods of measuring cost-effectiveness of health interventions as well as
      test a variety of scenarios to reduce the risk factors associated with selected
      chronic diseases. The modelling projections could be used to inform decisions and
      policies that will implement the best course of action to curb the rising
      incidence of chronic diseases.

PMID- 24886109
TI  - Fabry nephropathy: a review - how can we optimize the management of Fabry
      nephropathy?
AB  - Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations
      in the gene encoding the enzyme alpha-galactosidase A. Complete or partial
      deficiency in this enzyme leads to intracellular accumulation of
      globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types
      throughout the body, including the kidney. Progressive accumulation of Gb3 in
      podocytes, epithelial cells and the tubular cells of the distal tubule and loop
      of Henle contribute to the renal symptoms of Fabry disease, which manifest as
      proteinuria and reduced glomerular filtration rate leading to chronic kidney
      disease and progression to end-stage renal disease. Early diagnosis and timely
      initiation of treatment of Fabry renal disease is an important facet of disease
      management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase
      alfa, Replagal(r), Shire; agalsidase beta, Fabrazyme(r), Genzyme) as part of a
      comprehensive strategy to prevent complications of the disease, may be beneficial
      in stabilizing renal function or slowing its decline. Early initiation of ERT may
      also be more effective than initiating therapy in patients with more advanced
      disease. Several strategies are required to complement the use of ERT and treat
      the myriad of associated symptoms and organ involvements. In particular, patients
      with renal Fabry disease are at risk of cardiovascular events, such as high blood
      pressure, cardiac arrhythmias and stroke. This review discusses the management of
      renal involvement in Fabry disease, including diagnosis, treatments, and follow
      up, and explores recent advances in the use of biomarkers to assist with
      diagnosis, monitoring disease progression and response to treatment. 

PMID- 24886111
TI  - Abdominal wall reconstruction with components separation and mesh reinforcement
      in complex hernia repair.
AB  - BACKGROUND: Abdominal closure in the presence of enterocutaneous fistula, stoma
      or infection can be challenging. A single-surgeon's experience of performing
      components separation abdominal reconstruction and reinforcement with mesh in the
      difficult abdomen is presented. METHODS: Medical records from patients undergoing
      components separation and reinforcement with hernia mesh at Royal Liverpool
      Hospital from 2009 to 2012 were reviewed. Patients were classified by the Ventral
      Hernia Working Group (VHWG) grading system. Co-morbidities, previous surgeries,
      specific type of reconstruction technique, discharge date, complications and
      hernia recurrence were recorded. RESULTS: Twenty-three patients' (15 males, 8
      females) notes were reviewed. Median age was 57 years (range 20-76 years). Median
      follow-up at the time of review was 17 months (range 2-48 months). There were 13
      grade III hernias and 10 grade IV hernias identified. Synthetic mesh was placed
      to reinforce the abdomen in 6 patients, cross-linked porcine dermis was used in
      3, and a Biodesign(r) Hernia Graft was placed in 14. Complications included wound
      infection (13%), superficial wound dehiscence (22%), seroma formation (22%) and
      stoma complications (9%). To date, hernias have recurred in 3 patients (13%).
      CONCLUSIONS: Components separation and reinforcement with biological mesh is a
      successful technique in the grade III and IV abdomen with acceptable rate of
      recurrence and complications.

PMID- 24886112
TI  - Association of intestinal malrotation and Bochdalek hernia in an adult: a case
      report.
AB  - BACKGROUND: Late presentations of congenital diaphragmatic hernia are rare and
      differ from the classic neonatal presentation. The association with other
      congenital malformations in children, mainly intestinal malrotation, is well
      documented. The diagnosis of this association in adults is very rare, and depends
      on a high degree of suspicion. CASE PRESENTATION: We report a case of a 50-year
      old female Caucasian patient with a previous history of intestinal malrotation
      diagnosed in adolescence and treated conservatively. She was referred to the
      hospital with signs and symptoms of intestinal obstruction. The patient undertook
      computed tomography that confirmed small bowel obstruction with no obvious cause,
      and a right subphrenic abscess with right empyema was also present. An
      exploratory laparotomy was performed that revealed an intestinal malrotation
      associated with a right gangrenous and perforated Bochdalek hernia. Resection of
      the affected small bowel, closure of the Bochdalek foramen and the Ladd procedure
      were carried out. CONCLUSION: This case shows a rare association of two rare
      conditions in adults, and highlights the challenge in reaching the diagnosis and
      management options.

PMID- 24886113
TI  - Perceived economic situation, but not education level, is associated with
      disability prevalence in the Spanish elderly: observational study.
AB  - BACKGROUND: The aim of this paper is to ascertain if the subjective perception of
      the economic situation of a household is associated with the prevalence of
      disability in old age, net of education level. Subjective economic perception is
      less non-response biased. Knowing if the self-perceived economic situation is
      related to disability over and above education level has important implications
      both for understanding the mechanisms that lead to disability and for selecting
      policies to reduce it. METHODS: This is a transversal study based on the pilot of
      the ELES survey, which is a representative survey of non-institutionalised
      Spaniards aged 50 and over. Only individuals whose job income levels were fixed
      before becoming disabled were selected to avoid the main source of reverse
      causality. Disability was defined as having difficulty in carrying out any of 12
      activities of daily living. Education level, difficulty in making ends meet, self
      perceived relative economic position of the household, age, gender, psychological
      disposition, and alcohol and tobacco consumption were introduced as independent
      variables in binary logistic models. RESULTS: The working sample is made up of
      704 individuals of aged 60 and over. The subjective household economic situation,
      measured in two different ways, is strongly and consistently related with the
      prevalence of disability net of age, gender, education level and psychological
      disposition. After adjusting for age and gender, education level is no longer
      associated with disability. However, having economic difficulties has the same
      effect on disability prevalence as being 10 years older, or being a woman instead
      of a man. CONCLUSIONS: As the economic situation of the elderly is much easier to
      improve than their formal education, our findings support feasible interventions
      which could lead to a reduction in the prevalence of disability.

PMID- 24886114
TI  - Whole lung lavage combined with Granulocyte-macrophage colony stimulating factor
      inhalation for an adult case of refractory pulmonary alveolar proteinosis.
AB  - BACKGROUND: Whole-lung lavage (WLL) is classically the first-line treatment for
      symptomatic pulmonary alveolar proteinosis (PAP). However, some patients require
      multiple WLLs because of refractory nature of their PAP. In this instance, these
      patients may benefit from new treatment regimens, and new therapies should be
      tried for these patients. CASE PRESENTATION: We describe a 47-year-old Chinese
      woman who was confidently diagnosed with pulmonary alveolar proteinosis (PAP)
      after bronchoalveolar lavage and transbronchial lung biopsy. The patient received
      four sessions of bilateral whole lung lavage (WLL) and one session of WLL in
      combination with plasmapheresis, each only producing short-term symptomatic
      relief. The patient was given a trial of combination therapy, which consisted of
      WLL and Granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation. The
      patient showed a gradual improvement in oxygenation and her daily activity, as
      well as a dramatic improvement in her pulmonary CT examination. CONCLUSION:
      Bilateral WLL, in combination with GM-CSF inhalation, may be an effective
      treatment option for severe refractory PAP.

PMID- 24886115
TI  - A torted wandering spleen: a case report.
AB  - INTRODUCTION: A torted wandering spleen is a rare clinical occurrence with fewer
      than 500 cases reported and an incidence of less than 0.2%. It is brought about
      through laxity of the gastrosplenic and splenorenal ligaments; however, the
      precise aetiology remains unknown. It can prove to be a diagnostic challenge with
      high mortality if misdiagnosed. CASE PRESENTATION: We present the case of a 27
      year-old woman of Arabic ethnicity, who complained of a short history of severe
      abdominal pain with the background of recurrent abdominal pain and vomiting. An
      abdominal computerized tomography scan revealed a torted wandering spleen. This
      required a splenectomy due to splenic infarction. CONCLUSION: This report
      highlights the investigations and management necessary for a patient who presents
      with an ischaemic torted wandering spleen.

PMID- 24886116
TI  - A written self-help intervention for depressed adults comparing behavioural
      activation combined with physical activity promotion with a self-help
      intervention based upon behavioural activation alone: study protocol for a
      parallel group pilot randomised controlled trial (BAcPAc).
AB  - BACKGROUND: Challenges remain to find ways to support patients with depression
      who have low levels of physical activity (PA) to overcome perceived barriers and
      enhance the perceived value of PA for preventing future relapse. There is an
      evidence-base for behavioural activation (BA) for depression, which focuses on
      supporting patients to restore activities that have been avoided, but
      practitioners have no specific training in promoting PA. We aimed to design and
      evaluate an integrated BA and PA (BAcPAc) practitioner-led, written, self-help
      intervention to enhance both physical and mental health. METHODS/DESIGN: This
      study is informed by the Medical Research Council Complex Intervention Framework
      and describes a protocol for a pilot phase II randomised controlled trial (RCT)
      to test the feasibility and acceptability of the trial methods to inform a
      definitive phase III RCT. Following development of the augmented written self
      help intervention (BAcPAc) incorporating behavioural activation with physical
      activity promotion, depressed adults are randomised to receive up to 12 sessions
      over a maximum of 4 months of either BAcPAc or behavioural activation alone
      within a written self-help format, which represents treatment as usual. The study
      is located within two 'Improving Access to Psychological Therapies' services in
      South West England, with both written self-help interventions supported by mental
      health paraprofessionals. Measures assessed at 4, 9, and 12 month follow-up
      include the following: CIS-R, PHQ-9, accelerometer recorded (4 months only) and
      self-reported PA, body mass index, blood pressure, Insomnia Severity Index,
      quality of life, and health and social care service use. Process evaluation will
      include analysis of recorded support sessions and patient and practitioner
      interviews. At the time of writing the study has recruited 60 patients.
      DISCUSSION: The feasibility outcomes will inform a definitive RCT to assess the
      clinical and cost-effectiveness of the augmented BAcPAc written self-help
      intervention to reduce depression and depressive relapse, and bring about
      improvements across a range of physical health outcomes. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN74390532, 26.03.2013.

PMID- 24886117
TI  - Population pharmacokinetics of mefloquine, administered as a fixed-dose
      combination of artesunate-mefloquine in Indian patients for the treatment of
      acute uncomplicated Plasmodium falciparum malaria.
AB  - BACKGROUND: Fixed-dose combinations of artemisinin combination therapy are
      strongly recommended to facilitate drug administration and compliance. New fixed
      dose combinations must nevertheless be evaluated in relevant populations in terms
      of efficacy and pharmacokinetics. METHODS: A single-arm, open-label, clinical
      trial was performed in Indian patients with acute uncomplicated Plasmodium
      falciparum malaria to investigate the efficacy and the pharmacokinetics of
      mefloquine when combined with artesunate in a fixed-dose combination (400/200 mg
      of mefloquine base/artesunate). The pharmacokinetic analysis was performed using
      a population approach. RESULTS: Seventy-seven patients were included in the
      study. Mefloquine pharmacokinetics obeys a two-compartment model with first-order
      absorption and elimination. Mean parameter estimates (% inter-individual
      variability) were as follows: 0.16 h(-1) (75%) for the absorption rate constant,
      1.13 L/h (30%) for the apparent plasma clearance, 271 L (21%) for the apparent
      central distribution volume, 344 L (54%) for the apparent peripheral distribution
      volume, and 1.43 L/h for the apparent distribution clearance. These values were
      consistent with the pharmacokinetic results described in Thai patients. No
      significant covariate was found for clearance. Body weight explained the inter
      individual variability of the apparent central and peripheral distribution
      volumes. The PCR-adjusted efficacy of the treatment was 100%. CONCLUSIONS: The
      lack of significant covariate explaining the inter-individual variability of
      mefloquine clearance, combined with the excellent efficacy, supports the use of
      the standard 200/400 mg of artesunate-mefloquine fixed-dose combination in Indian
      patients with uncomplicated P. falciparum malaria. TRIAL REGISTRATION:  CLINICAL
      TRIAL REGISTRATION: ISRCTN70618692.

PMID- 24886118
TI  - De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner
      syndrome in two unrelated individuals identified by clinical exome sequencing.
AB  - BACKGROUND: Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a
      variety of dysmorphic facial and skeletal features, characteristic hypertrichosis
      cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and
      intellectual disability. [MIM#: 605130]. Here we report two unrelated children
      for whom clinical exome sequencing of parent-proband trios was performed at UCLA,
      resulting in a molecular diagnosis of WSS and atypical clinical presentation.
      CASE PRESENTATION: For patient 1, clinical features at 9 years of age included
      developmental delay, craniofacial abnormalities, and multiple minor anomalies.
      Patient 2 presented at 1 year of age with developmental delay, microphthalmia,
      partial 3-4 left hand syndactyly, and craniofacial abnormalities. A de novo
      missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were
      identified in the KMT2A gene in patients 1 and 2, respectively. CONCLUSIONS:
      Based on the clinical and molecular findings, both patients appear to have novel
      presentations of WSS. As the hallmark hypertrichosis cubiti was not initially
      appreciated in either case, this syndrome was not suspected during the clinical
      evaluation. This report expands the phenotypic spectrum of the clinical
      phenotypes and KMT2A variants associated with WSS.

PMID- 24886119
TI  - A policy-driven multifaceted approach for early childhood physical fitness
      promotion: impacts on body composition and physical fitness in young Chinese
      children.
AB  - BACKGROUND: The prevalence of obesity increased while certain measures of
      physical fitness deteriorated in preschool children in China over the past
      decade. This study tested the effectiveness of a multifaceted intervention that
      integrated childcare center, families, and community to promote healthy growth
      and physical fitness in preschool Chinese children. METHODS: This 12-month study
      was conducted using a quasi-experimental pretest/posttest design with comparison
      group. The participants were 357 children (mean age = 4.5 year) enrolled in three
      grade levels in two childcare centers in Beijing, China. The intervention
      included: 1) childcare center intervention (physical activity policy changes,
      teacher training, physical education curriculum and food services training), 2)
      family intervention (parent education, internet website for support, and family
      events), and 3) community intervention (playground renovation and community
      health promotion events). The study outcome measures included body composition
      (percent body fat, fat mass, and muscle mass), Body Mass Index (BMI) and BMI z
      score and physical fitness scores in 20-meter agility run (20M-AR), broad jump
      for distance (BJ), timed 10-jumps, tennis ball throwing (TBT), sit and reach
      (SR), balance beam walk (BBW), 20-meter crawl (20M-C)), 30-meter sprint (30M-S))
      from a norm referenced test. Measures of process evaluation included monitoring
      of children's physical activity (activity time and intensity) and food
      preparation records, and fidelity of intervention protocol implementation.
      RESULTS: Children in the intervention center significantly lowered their body fat
      percent (-1.2%, p < 0.0001), fat mass (-0.55 kg, p <0.0001), and body weight
      (0.36 kg, p <0.02) and increased muscle mass (0.48 kg, p <0.0001), compared to
      children in the control center. They also improved all measures of physical
      fitness except timed 10-jumps (20M-AR: -0.74 seconds, p < 0.0001; BJ: 8.09 cm, p
      < 0.0001; TBT: 0.52 meters, p < 0.006; SR: 0.88 cm, p < 0.03; BBW: -2.02 seconds,
      p <0.0001; 30M-S: -0.45 seconds, p < 0.02; 20M-C: -3.36 seconds, p < 0.0001).
      Process evaluation data showed that the intervention protocol was implemented
      with high fidelity. CONCLUSIONS: The study demonstrated that a policy-driven
      multi-faceted intervention can improve preschool children's body composition and
      physical fitness. Program efficacy should be tested in a randomized trial. TRIAL
      REGISTRATION: ChiCTR-ONRC-14004143.

PMID- 24886120
TI  - Extrasynaptic GABAA receptors in mediodorsal thalamic nucleus modulate fear
      extinction learning.
AB  - BACKGROUND: The gamma-amino-butyric acid (GABA) system is a critical mediator of
      fear extinction process. GABA can induce "phasic" or "tonic" inhibition in
      neurons through synaptic or extrasynaptic GABAA receptors, respectively. However,
      role of the thalamic "tonic GABA inhibition" in cognition has not been explored.
      We addressed this issue in extinction of conditioned fear in mice. RESULTS: Here,
      we show that GABAA receptors in the mediodorsal thalamic nucleus (MD) modulate
      fear extinction. Microinjection of gabazine, a GABAA receptor antagonist, into
      the MD decreased freezing behavior in response to the conditioned stimulus and
      thus facilitated fear extinction. Interestingly, microinjection of THIP (4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a preferential agonist for the delta
      subunit of extrasynaptic GABAA receptors, into the MD attenuated fear extinction.
      In the opposite direction, an MD-specific knock-out of the extrasynaptic GABAA
      receptors facilitated fear extinction. CONCLUSIONS: Our results suggest that
      "tonic GABA inhibition" mediated by extrasynaptic GABAA receptors in MD neurons,
      suppresses fear extinction learning. These results raise a possibility that
      pharmacological control of tonic mode of GABAA receptor activation may be a
      target for treatment of anxiety disorders like post-traumatic stress disorder.

PMID- 24886121
TI  - Consultant psychiatrists' experiences of and attitudes towards shared decision
      making in antipsychotic prescribing, a qualitative study.
AB  - BACKGROUND: Shared decision making represents a clinical consultation model where
      both clinician and service user are conceptualised as experts; information is
      shared bilaterally and joint treatment decisions are reached. Little previous
      research has been conducted to assess experience of this model in psychiatric
      practice. The current project therefore sought to explore the attitudes and
      experiences of consultant psychiatrists relating to shared decision making in the
      prescribing of antipsychotic medications. METHODS: A qualitative research design
      allowed the experiences and beliefs of participants in relation to shared
      decision making to be elicited. Purposive sampling was used to recruit
      participants from a range of clinical backgrounds and with varying length of
      clinical experience. A semi-structured interview schedule was utilised and was
      adapted in subsequent interviews to reflect emergent themes.Data analysis was
      completed in parallel with interviews in order to guide interview topics and to
      inform recruitment. A directed analysis method was utilised for interview
      analysis with themes identified being fitted to a framework identified from the
      research literature as applicable to the practice of shared decision making.
      Examples of themes contradictory to, or not adequately explained by, the
      framework were sought. RESULTS: A total of 26 consultant psychiatrists were
      interviewed. Participants expressed support for the shared decision making model,
      but also acknowledged that it was necessary to be flexible as the clinical
      situation dictated. A number of potential barriers to the process were perceived
      however: The commonest barrier was the clinician's beliefs regarding the service
      users' insight into their mental disorder, presented in some cases as an absolute
      barrier to shared decision making. In addition factors external to the clinician 
      service user relationship were identified as impacting on the decision making
      process, including; environmental factors, financial constraints as well as
      societal perceptions of mental disorder in general and antipsychotic medication
      in particular. CONCLUSIONS: This project has allowed identification of potential
      barriers to shared decision making in psychiatric practice. Further work is
      necessary to observe the decision making process in clinical practice and also to
      identify means in which the identified barriers, in particular 'lack of insight',
      may be more effectively managed.

PMID- 24886122
TI  - Knowledge, attitude and practices regarding HIV/AIDS among adult fishermen in
      coastal areas of Karachi.
AB  - BACKGROUND: Migrant populations are at high risk of Human Immuno Deficiency Virus
      infection (HIV) and Acquired Immunodeficiency Syndrome (AIDS). Studies of
      HIV/AIDS knowledge, attitudes and practices among fishermen in developing
      countries have shown gaps in knowledge and fear of contagion with ambivalent
      attitudes towards HIV/AIDS and inconsistent universal precautions adherence. The
      aim of this study was to determine the knowledge, attitude and practices
      regarding HIV/AIDS among adult fishermen in a coastal area of Karachi, Pakistan.
      METHODS: Community based cross sectional study was conducted among fishermen in
      coastal area of Karachi from June to September 2012. A total of 297 adult
      fishermen were selected by using simple random sampling technique from different
      sectors of coastal village. Data were collected using a structured validated
      questionnaire. The frequency distribution of both dependent and independent
      variables were worked out. Comparisons of knowledge, attitude and practices
      regarding HIV/AIDS by socio-demographic characteristics were made using logistic
      regression. RESULTS: Out of 297 fishermen, majority had in-appropriate knowledge
      (93.6%), negative attitude (75.8%) and less adherent sexual practices (91.6%). In
      univariate analysis, lower education and higher income were significantly
      associated (OR 2.25, 95% CI, 1.11, 4.55), (OR = 3.04 CI 1.03-9.02, p value 0.04)
      with negative attitude and un-safe practices towards HIV/AIDS respectively,
      whereas no significant association of socio-economic characteristics with
      knowledge, attitude and practices were observed in multivariate analysis.
      CONCLUSIONS: This study suggests that fishermen had very poor knowledge, negative
      attitudes towards HIV and AIDS and had unsafe sexual practices which suggest that
      they lack the basic understanding of HIV/AIDS infection. Extensive health
      education campaign should be provided to the vulnerable sections of the society
      for the control of HIV/AIDS.

PMID- 24886123
TI  - Physical activity is associated with reduced risk of esophageal cancer,
      particularly esophageal adenocarcinoma: a systematic review and meta-analysis.
AB  - BACKGROUND: Physical activity has been inversely associated with risk of several
      cancers. We performed a systematic review and meta-analysis to evaluate the
      association between physical activity and risk of esophageal cancer (esophageal
      adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). METHODS:
      We conducted a comprehensive search of bibliographic databases and conference
      proceedings from inception through February 2013 for observational studies that
      examined associations between recreational and/or occupational physical activity
      and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95%
      confidence intervals (CI) were estimated using the random-effects model. RESULTS:
      The analysis included 9 studies (4 cohort, 5 case-control) reporting 1,871 cases
      of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that
      the risk of esophageal cancer was 29% lower among the most physically active
      compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89),
      with moderate heterogeneity (I2 = 47%). On histology-specific analysis, physical
      activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of
      EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2 = 0%). There
      were only 3 studies reporting the association between physical activity and risk
      of ESCC with conflicting results, and the meta-analysis demonstrated a null
      association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across
      study design, geographic location and study quality, with a non-significant trend
      towards a dose-response relationship. CONCLUSIONS: Meta-analysis of published
      observational studies indicates that physical activity may be associated with
      reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on
      increasing physical activity may decrease the global burden of EAC.

PMID- 24886124
TI  - Community perceptions of unintentional child injuries in Makwanpur district of
      Nepal: a qualitative study.
AB  - BACKGROUND: In Nepal, childhood unintentional injury is an emerging public health
      problem but it has not been prioritised on national health agenda. There is lack
      of literature on community perceptions about child injuries. This study has
      explored community perceptions about child injuries and how injuries can be
      prevented. METHODS: Focus group discussions were conducted with mothers, school
      students and community health volunteers from urban and rural parts of Makwanpur
      district in Nepal. FGDs were conducted in Nepali languages. These were recorded,
      transcribed and translated into English. A theoretical framework was identified
      and thematic analysis conducted. RESULTS: Three focus group discussions, with a
      total of 27 participants, took place. Participants were able to identify examples
      of child injuries which took place in their community but these generally related
      to fatal and severe injuries. Participants identified risk factors such as the
      child's age, gender, behaviours and whether they had been supervised.
      Consequences of injuries such as physical and psychological effects, impact on
      household budgets and disturbance in household plans were identified. Suggestions
      were made about culturally appropriate prevention measures, and included;
      suitable supervision arrangements, separation of hazards and teaching about
      safety to the parents and children. CONCLUSION: Community members in Nepal can
      provide useful information about childhood injuries and their prevention but this
      knowledge is not transferred into action. Understanding community perceptions
      about injuries and their prevention can contribute to the development of
      preventive interventions in low income settings.

PMID- 24886125
TI  - Complete traumatic main pancreatic duct disruption treated endoscopically: a case
      report.
AB  - INTRODUCTION: Pancreatic injury is uncommon and the management remains
      controversial. The integrity of the main pancreatic duct is considered the most
      important determinant for prognosis. CASE PRESENTATION: A 19-year-old Greek man
      was referred to our tertiary referral centre due to blunt abdominal trauma and an
      associated grade III pancreatic injury. He was haemodynamically stable and his
      initial treatment was conservative. Due to deterioration in his clinical
      symptomatology he underwent an endoscopy 20 days postinjury, where a stent was
      placed in the proximal pancreatic duct remnant and a bulging fluid collection of
      the lesser sac was drained transgastrically. He made an uneventful recovery and
      remains well 7 months postinjury, but a stricture with upstream dilatation of his
      main pancreatic duct has developed. CONCLUSIONS: The clinical status of the
      patient rather than the grade of pancreatic injury should be the principal
      determinant to guide treatment. Endoscopic stenting and drainage is an attractive
      minimally invasive procedure and it may obviate the need for surgery. However,
      further investigation is required regarding the safety and outcome.

PMID- 24886128
TI  - Validation of self-reported weights and heights in the avoiding diabetes after
      pregnancy trial (ADAPT).
AB  - BACKGROUND: Randomized controlled trials that test the effectiveness of mobile
      health-based weight loss programs are attractive to participants, funders, and
      researchers because of the low implementation cost, minimal participant burden,
      and the ability to recruit participants from longer distances. Collecting weight
      data from geographically dispersed participants is a challenge. Relying on
      participant self-report is one approach to data collection, but epidemiologic
      studies indicate that self-reported anthropometric data may be inaccurate.
      METHODS: We provided women enrolled in a randomized controlled trial (RCT) of
      postpartum weight loss after gestational diabetes with a digital scale and
      training to collect and report weight via a web-based survey. To validate self
      reported weights and heights, we visited 30 randomly selected women in their
      homes, with a reference scale and stadiometer, a mean of 34 days after the self
      report. We ran linear regression models to identify characteristics that were
      associated with underreporting or overreporting of anthropometric measures.
      RESULTS: Of the 30 women we visited, 11 women (37%) were assigned to the weight
      loss intervention group and 19 women (63%) were in the control group. Mean age
      was 38.5 years (SD 4.5). The overall mean difference between participants' self
      reported weights and the weights obtained at their home visit was 0.70 kg
      (+1.92). Women assigned to the intervention group underreported their weight in
      comparison with the control group by 1.29 kg (95% CI -2.52, -0.06). The overall
      difference in collected to self-reported height was -0.56 cm (+/-1.91). No
      characteristics were associated with underreporting or overreporting of height.
      CONCLUSIONS: Our research suggests that by providing a digital scale and
      developing a weight collection protocol, researchers can train women to collect
      and record their own study weights with reasonable validity. To achieve the level
      of validity required for clinical trials, researchers should consider additional
      strategies to assure the validity of the data. TRIAL REGISTRATION: NCT01923350.

PMID- 24886127
TI  - The endogenous and reactive depression subtypes revisited: integrative animal and
      human studies implicate multiple distinct molecular mechanisms underlying major
      depressive disorder.
AB  - BACKGROUND: Traditional diagnoses of major depressive disorder (MDD) suggested
      that the presence or absence of stress prior to onset results in either
      'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines
      of research suggest that the biological underpinnings of 'reactive' or
      'endogenous' subtypes may also differ, resulting in differential response to
      treatment. We investigated this hypothesis by comparing the gene-expression
      profiles of three animal models of 'reactive' and 'endogenous' depression. We
      then translated these findings to clinical samples using a human post-mortem mRNA
      study. METHODS: Affymetrix mouse whole-genome oligonucleotide arrays were used to
      measure gene expression from hippocampal tissues of 144 mice from the Genome
      based Therapeutic Drugs for Depression (GENDEP) project. The study used four
      inbred mouse strains and two depressogenic 'stress' protocols (maternal
      separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression.
      Stress-related mRNA differences in mouse were compared with a parallel mRNA study
      using Flinders Sensitive and Resistant rat lines as a model of 'endogenous'
      depression. Convergent genes differentially expressed across the animal studies
      were used to inform candidate gene selection in a human mRNA post-mortem case
      control study from the Stanley Brain Consortium. RESULTS: In the mouse 'reactive'
      model, the expression of 350 genes changed in response to early stresses and 370
      in response to late stresses. A minimal genetic overlap (less than 8.8%) was
      detected in response to both stress protocols, but 30% of these genes (21) were
      also differentially regulated in the 'endogenous' rat study. This overlap is
      significantly greater than expected by chance. The VAMP-2 gene, differentially
      expressed across the rodent studies, was also significantly altered in the human
      study after correcting for multiple testing. CONCLUSIONS: Our results suggest
      that 'endogenous' and 'reactive' subtypes of depression are associated with
      largely distinct changes in gene-expression. However, they also suggest that the
      molecular signature of 'reactive' depression caused by early stressors differs
      considerably from that of 'reactive' depression caused by late stressors. A small
      set of genes was consistently dysregulated across each paradigm and in post
      mortem brain tissue of depressed patients suggesting a final common pathway to
      the disorder. These genes included the VAMP-2 gene, which has previously been
      associated with Axis-I disorders including MDD, bipolar depression, schizophrenia
      and with antidepressant treatment response. We also discuss the implications of
      our findings for disease classification, personalized medicine and case-control
      studies of MDD.

PMID- 24886126
TI  - Targeting of erbB3 receptor to overcome resistance in cancer treatment.
AB  - The erbB receptors, including the epidermal growth factor receptor (EGFR), erbB2
      (also known as HER2/neu), erbB3 (or HER3), and erbB4 (or HER4), are often
      aberrantly activated in a wide variety of human cancers. They are excellent
      targets for selective anti-cancer therapies because of their transmembrane
      location and pro-oncogenic activity. While several therapeutic agents against
      erbB2 and/or EGFR have been used in the treatment of human cancers with efficacy,
      there has been relatively less emphasis on erbB3 as a molecular target. Elevated
      expression of erbB3 is frequently observed in various malignancies, where it
      promotes tumor progression via interactions with other receptor tyrosine kinases
      (RTKs) due to its lack of or weak intrinsic kinase activity. Studies on the
      underlying mechanisms implicate erbB3 as a major cause of treatment failure in
      cancer therapy, mainly through activation of the PI-3 K/Akt, MEK/MAPK, and
      Jak/Stat signaling pathways as well as Src kinase. It is believed that inhibition
      of erbB3 signaling may be required to overcome therapeutic resistance and
      effectively treat cancers. To date, no erbB3-targeted therapy has been approved
      for cancer treatment. Targeting of erbB3 receptor with a monoclonal antibody (Ab)
      is the only strategy currently under preclinical study and clinical evaluation.
      In this review, we focus on the role of erbB3-initiated signaling in the
      development of cancer drug resistance and discuss the latest advances in
      identifying therapeutic strategies inactivating erbB3 to overcome the resistance
      and enhance efficacy of cancer therapeutics. 

PMID- 24886129
TI  - Insecticide resistance in Anopheles arabiensis in Sudan: temporal trends and
      underlying mechanisms.
AB  - BACKGROUND: Malaria vector control in Sudan relies mainly on indoor residual
      spraying (IRS) and the use of long lasting insecticide treated bed nets (LLINs).
      Monitoring insecticide resistance in the main Sudanese malaria vector, Anopheles
      arabiensis, is essential for planning and implementing an effective vector
      control program in this country. METHODS: WHO susceptibility tests were used to
      monitor resistance to insecticides from all four WHO-approved classes of
      insecticide at four sentinel sites in Gezira state over a three year period.
      Insecticide resistance mechanisms were studied using PCR and microarray analyses.
      RESULTS: WHO susceptibility tests showed that Anopheles arabiensis from all sites
      were fully susceptible to bendiocarb and fenitrothion for the duration of the
      study (2008-2011). However, resistance to DDT and pyrethroids was detected at
      three sites, with strong seasonal variations evident at all sites. The 1014 F kdr
      allele was significantly associated with resistance to pyrethroids and DDT (P <
      0.001) with extremely high effects sizes (OR > 7 in allelic tests). The 1014S
      allele was not detected in any of the populations tested. Microarray analysis of
      the permethrin-resistant population of An. arabiensis from Wad Medani identified
      a number of metabolic genes that were significantly over-transcribed in the field
      collected resistant samples when compared to the susceptible Sudanese An.
      arabiensis Dongola strain. These included CYP6M2 and CYP6P3, two genes previously
      implicated in pyrethroid resistance in Anopheles gambiae s.s, and the epsilon
      class glutathione-S-transferase, GSTe4. CONCLUSIONS: These data suggest that both
      target-site mechanisms and metabolic mechanisms play an important role in
      conferring pyrethroid resistance in An. arabiensis from Sudan. Identification in
      An. arabiensis of candidate loci that have been implicated in the resistance
      phenotype in An. gambiae requires further investigation to confirm the role of
      these genes.

PMID- 24886130
TI  - Epidemiology, species distribution and outcome of nosocomial Candida spp.
      bloodstream infection in Shanghai.
AB  - BACKGROUND: Yeasts, mostly Candida, are important causes of bloodstream
      infections (BSI), responsible for significant mortality and morbidity among
      hospitalized patients. The epidemiology and species distribution vary from
      different regions. The goals of this study were to report the current
      epidemiology of Candida BSI in a Shanghai Teaching Hospital and estimate the
      impact of appropriate antifungal therapy on the outcome. METHODS: From January
      2008 to December 2012, all consecutive patients who developed Candida BSI at
      Ruijin University Hospital were enrolled. Underlying diseases, clinical severity,
      species distribution, antifungal therapy and its impact on the outcome were
      analyzed. RESULTS: A total of 121 episodes of Candida BSI were identified, with
      an incidence of 0.32 episodes/1,000 admissions (0.21 in 2008 and 0.42 in 2012)
      The proportion of candidemia caused by non-albicans species (62.8%), including C.
      parapsilosis (19.8%), C. tropicalis (14.9%), C. glabrata (7.4%), C.
      guilliermondii (5.8%), C. sake (5.0%) was higher than that of candidemia caused
      by C. albicans (37.2%). The overall crude 28-day mortality was 28.1% and
      significantly reduced with appropriate empiric antifungal therapy administered
      within 5 days (P = 0.006). Advanced age (OR 1.04; P = 0.014), neutropenia <
      500/mm3 (OR 17.44; P < 0.001) were independent risk factors for 28-day mortality,
      while appropriate empiric antifungal therapy (OR 0.369; P = 0.035) was protective
      against 28-day mortality. CONCLUSION: The epidemiology of candidemia in Shanghai
      differed from that observed in Western countries. Appropriate empiric antifungal
      therapy influenced the short-term survival.

PMID- 24886131
TI  - Multidimensional mutual information methods for the analysis of covariation in
      multiple sequence alignments.
AB  - BACKGROUND: Several methods are available for the detection of covarying
      positions from a multiple sequence alignment (MSA). If the MSA contains a large
      number of sequences, information about the proximities between residues derived
      from covariation maps can be sufficient to predict a protein fold. However, in
      many cases the structure is already known, and information on the covarying
      positions can be valuable to understand the protein mechanism and dynamic
      properties. RESULTS: In this study we have sought to determine whether a
      multivariate (multidimensional) extension of traditional mutual information (MI)
      can be an additional tool to study covariation. The performance of two
      multidimensional MI (mdMI) methods, designed to remove the effect of
      ternary/quaternary interdependencies, was tested with a set of 9 MSAs each
      containing <400 sequences, and was shown to be comparable to that of the newest
      methods based on maximum entropy/pseudolikelyhood statistical models of protein
      sequences. However, while all the methods tested detected a similar number of
      covarying pairs among the residues separated by < 8 A in the reference X-ray
      structures, there was on average less than 65% overlap between the top scoring
      pairs detected by methods that are based on different principles. CONCLUSIONS:
      Given the large variety of structure and evolutionary history of different
      proteins it is possible that a single best method to detect covariation in all
      proteins does not exist, and that for each protein family the best information
      can be derived by merging/comparing results obtained with different methods. This
      approach may be particularly valuable in those cases in which the size of the MSA
      is small or the quality of the alignment is low, leading to significant
      differences in the pairs detected by different methods.

PMID- 24886132
TI  - New concept of scapholunate dissociation treatment and novel modification of
      Brunelli procedure - anatomical study.
AB  - BACKGROUNDS: This paper describes a novel method in treatment of scapholunate
      dissociation accompanied with rotatory subluxation of the scaphoid. The idea of
      this method is to create a kind of axial lever that can fully reconstruct
      anatomical relationship between the scaphoid and the lunate, with no involvement
      of extrinsic ligaments, and with simultaneous restriction of pathological
      alignment of the scaphoid. Based on this technique, we have also proposed a new
      modification of Brunelli procedure in scapholunate dissociation with rotatory
      subluxation of the scaphoid and dorsal intercalated segmental instability.
      METHODS: At the initial stage of the study, 20 human wrists fixed in Ethanol were
      used, followed by 12 fresh human wrists used in part two. The first stage
      included functional, biomechanical and strength tests carried out by means of a 5
      kg load and intended to find the most anatomical and durable treatment method.
      The second stage involved testing the proposed methods on fresh cadaver wrists.
      RESULTS: We have discovered that the new method is able to recreate anatomical
      forces and properties of scapholunate ligament; what's more, it can also prevent
      rotatory subluxation of the scaphoid. The performed strength tests have proven
      that it is possible to treat scapholunate instability also in case of dorsal
      intercalated segmental instability. CONCLUSIONS: We highly recommend using both
      the new technique and the new modification of Brunelli procedure for treatment of
      scapholunate dissociation in both dynamic and static instabilities.

PMID- 24886134
TI  - Community-level determinants of obesity: harnessing the power of electronic
      health records for retrospective data analysis.
AB  - BACKGROUND: Obesity and overweight are multifactorial diseases that affect two
      thirds of Americans, lead to numerous health conditions and deeply strain our
      healthcare system. With the increasing prevalence and dangers associated with
      higher body weight, there is great impetus to focus on public health strategies
      to prevent or curb the disease. Electronic health records (EHRs) are a powerful
      source for retrospective health data, but they lack important community-level
      information known to be associated with obesity. We explored linking EHR and
      community data to study factors associated with overweight and obesity in a
      systematic and rigorous way. METHODS: We augmented EHR-derived data on 62,701
      patients with zip code-level socioeconomic and obesogenic data. Using a
      multinomial logistic regression model, we estimated odds ratios and 95%
      confidence intervals (OR, 95% CI) for community-level factors associated with
      overweight and obese body mass index (BMI), accounting for the clustering of
      patients within zip codes. RESULTS: 33, 31 and 35 percent of individuals had BMIs
      corresponding to normal, overweight and obese, respectively. Models adjusted for
      age, race and gender showed more farmers' markets/1,000 people (0.19, 0.10-0.36),
      more grocery stores/1,000 people (0.58, 0.36-0.93) and a 10% increase in
      percentage of college graduates (0.80, 0.77-0.84) were associated with lower odds
      of obesity. The same factors yielded odds ratios of smaller magnitudes for
      overweight. Our results also indicate that larger grocery stores may be inversely
      associated with obesity. CONCLUSIONS: Integrating community data into the EHR
      maximizes the potential of secondary use of EHR data to study and impact obesity
      prevention and other significant public health issues.

PMID- 24886133
TI  - Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR)
      genetic variation is associated with ovarian hyperstimulation syndrome.
AB  - BACKGROUND: The objective of this investigation was to determine if kinase insert
      domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic
      variation was associated with the development of ovarian hyperstimulation
      syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).
      METHODS: This was a case-control study of 174 patients who underwent controlled
      ovarian stimulation. Patient blood samples were genotyped for single nucleotide
      polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome
      variables, SNP and haplotype frequencies were compared between control (n = 155)
      and OHSS (n = 19) groups. RESULTS: Patients who developed OHSS had significantly
      higher response markers (estradiol levels of the day of hCG administration,
      number of follicles developed, number of eggs retrieved) than control patients.
      When adjusted for age and self-identified race, the rs2305945 G/T genotype was
      associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of
      developing OHSS using an overdominant model. The rs2305945 G/T variant was also
      associated with decreased COH response (number of follicles, number of eggs
      retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G)
      haplotype was associated with both decreased COH response and OHSS risk
      (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031). CONCLUSIONS: The KDR
      receptor is believed to play a central role OHSS development and is a target for
      pharmacological prevention of OHSS. These results indicate that genetic variation
      in the KDR gene may impact individual risk of developing OHSS from COH. In
      addition, the rs2305948 SNP and C-T-G haplotype might serve as potential
      biomarkers for poor ovarian response to COH.

PMID- 24886135
TI  - Clinical malaria among pregnant women on combined insecticide treated nets (ITNs)
      and intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine in
      Yaounde, Cameroon.
AB  - BACKGROUND: Malaria remains a burden for pregnant women and the under 5.
      Intermittent preventive treatment of pregnant women (IPTp) for malaria with
      sulfadoxine - pyrimethamine (SP) has since replaced prophylaxis and legislation
      has been reinforced in the area of insecticide treated mosquito nets (ITNs) in
      Cameroon. Clinical malaria despite all these measures remains a problem. We
      compared the socio-obstetrical characteristics of women who developed clinical
      malaria and those who did not though in the same regimen. METHODS: A 5 - year
      nested cohort study (2007 - 2011 inclusive) at the tertiary level hospitals in
      Yaounde. Pregnant women who willingly accepted to participate in the study were
      enrolled at booking and three doses of SP were administered between 18 - 20 weeks
      of gestation, between 26-28 weeks and between 32 - 34 weeks. Those who developed
      clinical malaria were considered as cases and were compared for socio -
      obstetrical characteristics with those who did not. Venous blood was drawn from
      the women in both arms for parasite density estimation and identification and all
      the clinical cases were treated conventionally. RESULTS: Each arm had 166 cases
      and many women who developed clinical malaria were between 15 and 19 years (OR
      5.5, 95% CI 3.9 - 5.3, p < 0.001). They were of low gravidity (OR 6.5, 95% CI 3.8
      - 11.3, p < 0.001) as well as low parity (OR 4.6, 95% CI 2.7 - 7.9, p < 0.001).
      The cases were single women (OR 4.58, 95% CI 2.54 - 8.26, p < 0.001) and had
      attained only primary level of education (OR 4.6, 95% CI 2.8 - 7.9, p < 0.001).
      Gestational ages were between 20 to 30 weeks during clinical malaria (OR 6.8, 95%
      CI 4.1 - 11.7, p < 0.001). The time between the first and second dose of SP was
      longer than ten weeks in the cases (OR 5.5, 95% CI 3.2 - 9.3, p < 0.001) and
      parasite density was higher also among the cases (OR 6.9, 95% CI 5.9 - 12.1, p <
      0.001). CONCLUSION: Long spacing between the first and second dose of SP seemed
      to be responsible for clinical malaria in the cases.

PMID- 24886137
TI  - Measurement precision and biological variation of cranial arteries using
      automated analysis of 3 T magnetic resonance angiography.
AB  - BACKGROUND: Non-invasive magnetic resonance angiography (MRA) has facilitated
      repeated measurements of human cranial arteries in several headache and migraine
      studies. To ensure comparability across studies the same automated analysis
      software has been used, but the intra- and interobserver, day-to-day and side-to
      side variations have not yet been published. We hypothesised that the observer
      related, side-to-side, and day-to-day variations would be less than 10%. METHODS:
      Ten female participants were studied using high-resolution MRA on two study days
      separated by at least one week. Using the automated LKEB-MRA vessel wall analysis
      software arterial circumferences were measured by blinded observers. Each artery
      was analysed twice by each of the two different observers. The primary endpoints
      were to determine the intraclass correlation coefficient (ICC) and intra- an
      inter-observer, the day-to-day, and side-to-side variations of the circumference
      of the middle meningeal (MMA) and middle cerebral (MCA) arteries. RESULTS: We
      found an excellent intra- and interobserver agreement for the MMA (ICC: 0.909
      0.987) and for the MCA (ICC: 0.876-0.949). The coefficient of variance within
      observers was <=1.8% for MMA and <=3.1% for MCA; between observers <=3.4% (MMA)
      and <=4.1% (MCA); between days <=6.0% (MMA) and <=8.0% (MCA); between sides
      <=9.4% (MMA) and <=6.5% (MCA). CONCLUSION: The present study demonstrates a low
      (<5%) inter- and intraobserver variation using the automated LKEB-MRA vessel wall
      analysis software. Furthermore, the study also suggests that the day-to-day and
      side-to-side variations of the MMA and MCA circumferences are less than 10%.

PMID- 24886138
TI  - Target guided isolation, in-vitro antidiabetic, antioxidant activity and
      molecular docking studies of some flavonoids from Albizzia Lebbeck Benth. bark.
AB  - BACKGROUND: Albizzia Lebbeck Benth. is traditionally important plant and is
      reported to possess a variety of pharmacological actions. The present research
      exertion was undertaken to isolate and characterized the flavonoids from the
      extract of stem bark of Albizzia Lebbeck Benth. and to evaluate the efficacy of
      the isolated flavonoids on in-vitro models of type-II diabetes. Furthermore, the
      results of in-vitro experimentation inveterate by the molecular docking studies
      of the isolated flavonoids on alpha-glucosidase and alpha-amylase enzymes.
      METHODS: Isolation of the flavonoids from the methanolic extract of stem bark of
      A. Lebbeck Benth was executed by the Silica gel (Si) column chromatography to
      yield different fractions. These fractions were then subjected to purification to
      obtain three important flavonoids. The isolated flavonoids were then structurally
      elucidated with the assist of 1H-NMR, 13C-NMR, and Mass spectroscopy. In-vitro
      experimentation was performed with evaluation of alpha-glucosidase, alpha-amylase
      and DPPH inhibition capacity. Molecular docking study was performed with GLIDE
      docking software. RESULTS: Three flavonoids, (1) 5-deoxyflavone (geraldone), (2)
      luteolin and (3) Isookanin were isolated from the EtOAc fraction of the
      methanolic extract of Albizzia lebbeck Benth bark. (ALD). All the compounds
      revealed to inhibit the alpha-glucosidase and alpha-amylase enzymes in in-vitro
      investigation correlating to reduce the plasma glucose level. Molecular docking
      study radically corroborates the binding affinity and inhibition of alpha
      glucosidase and alpha-amylase enzymes. CONCLUSION: The present research exertion
      demonstrates the anti-diabetic and antioxidant activity of the important isolated
      flavonoids with inhibition of alpha-glucosidase, alpha-amylase and DPPH which is
      further supported by molecular docking analysis.

PMID- 24886139
TI  - Cytotoxic effects of Euterpe oleracea Mart. in malignant cell lines.
AB  - BACKGROUND: Euterpe oleracea Mart., a plant from the Amazon region, is commonly
      known as acai or jucara; it has high nutritional value and elevated levels of
      lipids, proteins, and minerals. Acai is an abundant and much consumed fruit by
      the Amazon local population, and studies have demonstrated that it is rich in
      phytochemicals with antioxidant, anti-inflammatory, and anticancer activities.
      Therefore, the aim of this study was to test this plant for anticancer activity
      in different human malignant cell lines. METHODS: Cell lines derived from breast
      and colorectal adenocarcinomas were treated with 10, 20, and 40 MUg/mL of bark,
      seed, and total acai fruit hydroalcoholic extracts for 24 and 48 h. After
      treatment, cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays, and cell morphological features were
      observed by light and transmission electron microscopy. The type of cell death
      was also evaluated. The data were analyzed statistically by one-way analysis of
      variance (ANOVA), followed by Dunnett's or Tukey's post hoc tests, as
      appropriate. RESULTS: We observed that of all the cell lines tested, MCF-7 was
      the only line that responded to acai treatment. The extracts caused significant
      reduction (p<0.01) in cell viability and altered cell morphological features by
      inducing the appearance of autophagic vacuoles, as observed by transmission
      electron microscopy. Furthermore, increased expression of LC3BII, a protein
      marker of autophagosome formation, was observed by western blotting. Caspase
      GloTM assays and morphologic observations by DAPI nuclear staining and
      transmission electron microscopy did not indicate any apoptotic events.
      CONCLUSIONS: The present study demonstrated that acai possesses antitumorigenic
      potential in the MCF-7 cell line. Further studies are needed to identify the
      compound (s) responsible for this cytotoxic activity and the molecular target in
      the cell. This discovery of the anticancer potential of acai may help in the
      development of chemopreventive drugs and may have therapeutic effects in the
      treatment of breast cancer.

PMID- 24886136
TI  - The rise of army ants and their relatives: diversification of specialized
      predatory doryline ants.
AB  - BACKGROUND: Army ants are dominant invertebrate predators in tropical and
      subtropical terrestrial ecosystems. Their close relatives within the dorylomorph
      group of ants are also highly specialized predators, although much less is known
      about their biology. We analyzed molecular data generated from 11 nuclear genes
      to infer a phylogeny for the major dorylomorph lineages, and incorporated fossil
      evidence to infer divergence times under a relaxed molecular clock. RESULTS:
      Because our results indicate that one subfamily and several genera of
      dorylomorphs are non-monophyletic, we propose to subsume the six previous
      dorylomorph subfamilies into a single subfamily, Dorylinae. We find the monophyly
      of Dorylinae to be strongly supported and estimate the crown age of the group at
      87 (74-101) million years. Our phylogenetic analyses provide only weak support
      for army ant monophyly and also call into question a previous hypothesis that
      army ants underwent a fundamental split into New World and Old World lineages.
      Outside the army ants, our phylogeny reveals for the first time many old,
      distinct lineages in the Dorylinae. The genus Cerapachys is shown to be non
      monophyletic and comprised of multiple lineages scattered across the Dorylinae
      tree. We recover, with strong support, novel relationships among these Cerapachys
      like clades and other doryline genera, but divergences in the deepest parts of
      the tree are not well resolved. We find the genus Sphinctomyrmex, characterized
      by distinctive abdominal constrictions, to consist of two separate lineages with
      convergent morphologies, one inhabiting the Old World and the other the New World
      tropics. CONCLUSIONS: While we obtain good resolution in many parts of the
      Dorylinae phylogeny, relationships deep in the tree remain unresolved, with major
      lineages joining each other in various ways depending upon the analytical method
      employed, but always with short internodes. This may be indicative of rapid
      radiation in the early history of the Dorylinae, but additional molecular data
      and more complete species sampling are needed for confirmation. Our phylogeny now
      provides a basic framework for comparative biological analyses, but much
      additional study on the behavior and morphology of doryline species is needed,
      especially investigations directed at the non-army ant taxa.

PMID- 24886140
TI  - LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola
      disease brains.
AB  - BACKGROUND: Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder
      characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused
      by a loss-of-function mutation of either DAP12 or TREM2. TREM2 and DAP12
      constitute a receptor/adaptor signaling complex expressed exclusively on
      osteoclasts, dendritic cells, macrophages, and microglia. Neuropathologically,
      NHD exhibits profound loss of myelin and accumulation of axonal spheroids,
      accompanied by intense gliosis accentuated in the white matter of the frontal and
      temporal lobes. At present, the molecular mechanism responsible for development
      of leukoencephalopathy in NHD brains remains totally unknown. METHODS: By
      immunohistochemistry, we studied the expression of microtubule-associated protein
      1 light chain 3 (LC3), an autophagosome marker, in 5 NHD and 12 control brains.
      RESULTS: In all NHD brains, Nogo-A-positive, CNPase-positive oligodendrocytes
      surviving in the non-demyelinated white matter intensely expressed LC3. They also
      expressed ubiquitin, ubiquilin-1, and histone deacetylase 6 (HDAC6) but did not
      express Beclin 1 or sequestosome 1 (p62). Substantial numbers of axonal spheroids
      were also labeled with LC3 in NHD brains. In contrast, none of oligodendrocytes
      expressed LC3 in control brains. Furthermore, surviving oligodendrocytes located
      at the demyelinated lesion edge of multiple sclerosis (MS) did not express LC3,
      whereas infiltrating Iba1-positive macrophages and microglia intensely expressed
      LC3 in MS lesions. CONCLUSIONS: These results propose a novel hypothesis that
      aberrant regulation of autophagy might induce oligodendrogliopathy causative of
      leukoencephalopathy in NHD brains.

PMID- 24886141
TI  - Gastrointestinal nematodes of dairy goats, anthelmintic resistance and practices
      of parasite control in Northern Italy.
AB  - BACKGROUND: Gastrointestinal nematodes (GINs) are one of the main constraints to
      ruminant production worldwide. Anthelmintic resistance (AR) has been reported in
      goats throughout Europe, yet little is known about the AR status in Italy. The
      aims of the study were: i) determine the frequency of AR in GINs in goat flocks
      in Northern Italy, Italy, ii) survey goat farmers on the current practices of
      parasite control, iii) update the species composition of the gastrointestinal
      helminthofauna. Thirty three flocks were enrolled and 1288 individual fecal
      samples were collected. Based on the egg per gram (EPG), 15 flocks were selected
      to evaluate the presence of AR in GINs with the Fecal Egg Count Reduction Test
      (FECRT). A questionnaire surveyed 110 dairy goat farmers to acquire information
      about farm management and drenching practices against GINs. Further, the
      gastrointestinal tracts of 42 goats were analyzed. RESULTS: The FECRs indicated
      that five of the 15 flocks had problems of AR, which was identified in all two of
      the anthelmintic classes tested. Resistance and suspected resistance was found in
      40% of the flocks selected for AR testing that were treated with benzimidazoles
      while 20% of the flocks treated with eprinomectin had resistant GINs.
      Teladorsagia/Trichostrongylus L3 were isolated from the post-treatment
      coprocultures of all flocks with resistance but not from the flock with suspected
      oxfendazole resistance. Treatments against helminths were performed once annually
      in 73.63% of the flocks, but 20.00% of farmers declared not regularly treating
      their goats every year. Annual treatments usually occurred in autumn or winter at
      dose rate for sheep. Te. circumcincta, H. contortus, Tr. colubriformis,
      Skrjabinema caprae and Oesophagostomum venulosum were the most abundant and
      prevalent species of the gastrointestinal tract. CONCLUSIONS: Strategies to
      prevent the development of AR should be widely adopted in Northern Italy.
      Further, farmers and practitioners should be educated about the importance of
      using the correct dose rates in goats. In addition, the presence of highly
      pathogenic GINs coupled with high worm burden in all sector of gastrointestinal
      tract and the prevalence values further suggest that improved diagnosis and
      active surveillance of GINs infection is needed.

PMID- 24886142
TI  - Immunobiotic Lactobacillus rhamnosus strains differentially modulate antiviral
      immune response in porcine intestinal epithelial and antigen presenting cells.
AB  - BACKGROUND: Previous findings suggested that Lactobacillus rhamnosus CRL1505 is
      able to increase resistance of children to intestinal viral infections. However,
      the intestinal cells, cytokines and receptors involved in the immunoregulatory
      effect of this probiotic strain have not been fully characterized. RESULTS: We
      aimed to gain insight into the mechanisms involved in the immunomodulatory effect
      of the CRL1505 strain and therefore evaluated in vitro the crosstalk between L.
      rhamnosus CRL1505, porcine intestinal epithelial cells (IECs) and antigen
      presenting cells (APCs) from swine Peyer's patches in order to deepen our
      knowledge about the mechanisms, through which this strain may help preventing
      viral diarrhoea episodes. L. rhamnosus CRL1505 was able to induce IFN-alpha and 
      beta in IECs and improve the production of type I IFNs in response to poly(I:C)
      challenge independently of Toll-like receptor (TLR)-2 or TLR9 signalling. In
      addition, the CRL1505 strain induced mRNA expression of IL-6 and TNF-alpha via
      TLR2 in IECs. Furthermore, the strain significantly increased surface molecules
      expression and cytokine production in intestinal APCs. The improved Th1 response
      induced by L. rhamnosus CRL1505 was triggered by TLR2 signalling and included
      augmented expression of MHC-II and co-stimulatory molecules and expression of IL
      1beta, IL-6, and IFN-gamma in APCs. IL-10 was also significantly up-regulated by
      CRL1505 in APCs. CONCLUSIONS: It was recently reviewed the emergence of TLR
      agonists as new ways to transform antiviral treatments by introducing panviral
      therapeutics with less adverse effects than IFN therapies. The use of L.
      rhamnosus CRL1505 as modulator of innate immunity and inductor of antiviral type
      I IFNs, IFN-gamma, and regulatory IL-10 clearly offers the potential to overcome
      this challenge.

PMID- 24886143
TI  - Using direct clinical observation to assess the quality of cesarean delivery in
      Afghanistan: an exploratory study.
AB  - BACKGROUND: As part of a National Emergency Obstetric and Newborn Care (EmONC)
      Needs Assessment, a special study was undertaken in July 2010 to examine the
      quality of cesarean deliveries in Afghanistan and examine the utility of direct
      clinical observation as an assessment method in low-resource settings. METHODS:
      This cross-sectional assessment of the quality of cesareans at 14 facilities in
      Afghanistan included a survey of surgeons regarding their routine cesarean
      practices, direct observation of 29 cesarean deliveries and comparison of
      observations with facility records for 34 additional cesareans conducted during
      the 3 days prior to the observation period at each facility. For both observed
      cases and record reviews, we assessed time intervals between specified points of
      care-arrival to the ward, first evaluation, detection of a complication, decision
      for cesarean, incision, and birth. RESULTS: All time intervals with the exception
      of "decision to skin incision" were longer in the record reviews than in observed
      cases. Prior cesarean was the most common primary indication for all cases. All
      mothers in both groups observed survived through one hour postpartum. Among
      newborns there were two stillbirths (7%) in observed births and seven (21%)
      record reviews. Although our sample is too small to show statistical
      significance, the difference is noteworthy. In six of the reviewed cesareans
      resulting in stillbirth, a fetal heart rate was recorded in the operating
      theater, although four were recorded as macerated. For the two fresh stillbirths,
      the cesarean surgeries were recorded as scheduled and not urgent. CONCLUSIONS:
      Direct observation of cesarean deliveries enabled us to assess a number of
      preoperative, postoperative, and intraoperative procedures that are often not
      described in medical records in low resource settings. Comparison of observations
      with findings from provider interviews and facility records allowed us to infer
      whether observed practices were typical of providers and facilities and detect
      potential Hawthorne effects.

PMID- 24886144
TI  - High short-term and long-term excess mortality in geriatric patients after hip
      fracture: a prospective cohort study in Taiwan.
AB  - BACKGROUND: Hip fracture has a high mortality rate, but the actual level of long
      term excess mortality and its impact on population-wide mortality remains
      controversial. The present prospective study investigated short- and long-term
      excess mortality after hip fractures with adjustment of other risk factors. We
      calculated the population attributable risk proportion (PARP) to assess the
      impact of each risk factor on excess mortality. METHODS: We recruited 217 elders
      with hip fractures and 215 age- and sex-matched patients without fractures from
      the geriatric department of the same hospital. The mean follow-up time was 46.1
      months (range: 35 to 57 months). We recorded data on 55 covariates, including
      baseline details about health, function, and bone mineral density. We used the
      multivariate Cox proportional hazards model to analyze hazard ratios (HRs) of
      short-term (<12 months follow-up) and long-term (? 2 months follow-up) excess
      mortality for each covariate and calculated their PARP. RESULTS: Patients with
      hip fractures had a higher short-term mortality than non-fractured patients, and
      the long-term excess mortality associated with hip fracture remained high. The
      significant risk factors for short-term mortality were hip fracture,
      comorbidities, and lower (below cutoff) Mini Mental State Examination score with
      HRs of 2.4, 2.3, and 2.3, respectively. Their PARPs were 44.7%, 38.1%, and 34.3%,
      respectively. The significant risk factors for long-term mortality were hip
      fracture (HR: 2.7; PARP: 48.0%), lower T-score (HR: 3.3; PARP: 36.2%), lower body
      mass index (HR: 2.5; PARP: 42.8%), comorbidities (HR: 2.1; PARP: 34.8%),
      difficulty in activities of daily living (HR: 1.9; PARP: 31.8%), and smoking (HR:
      2.5; PARP: 19.2%). CONCLUSIONS: After comprehensive adjustment, hip fracture was
      a significant risk factor and contributed the most to long-term as well as short
      term excess mortality. Its adequate prevention and treatment should be targeted.

PMID- 24886145
TI  - Community mobilization for malaria elimination: application of an open space
      methodology in Ruhuha sector, Rwanda.
AB  - BACKGROUND: Despite the significant reduction of malaria transmission in Rwanda,
      Ruhuha sector is still a highly endemic area for malaria. The objective of this
      activity was to explore and brainstorm the potential roles of various community
      stakeholders in malaria elimination. METHODS: Horizontal participatory approaches
      such as 'open space' have been deployed to explore local priorities, stimulate
      community contribution to project planning, and to promote local capacity to
      manage programmes. Two open space meetings were conducted with 62 and 82
      participants in years 1 and 2, respectively. Participants included purposively
      selected community and local organizations' representatives. RESULTS: Malaria was
      perceived as a health concern by the respondents despite the reported reduction
      in prevalence from 60 to 20% for cases at the local health centre. Some
      misconceptions of the cause of malaria and misuse of preventive strategies were
      noted. Poverty was deemed to be a contributing factor to malaria transmission,
      with suggestions that improvement of living conditions for poor families might
      help malaria reduction. Participants expressed willingness to contribute to
      malaria elimination and underscored the need for constant education,
      sensitization and mobilization towards malaria control in general. Active
      diagnosis, preventative strategies and prompt treatment of malaria cases were all
      mentioned by participants as ways to reduce malaria. Participants suggested that
      partnership of stakeholders at various levels could speed up programme
      activities. A community rewards system was deemed important to motivate engaged
      participants, i.e., community health workers and households. Establishment of
      malaria clubs in schools settings was also suggested as crucial to speed up
      community awareness and increase skills towards further malaria reduction.
      CONCLUSIONS: This bottom-up approach was found useful in engaging the local
      community, enabling them to explore issues related to malaria in the area and
      suggest solutions for sustainable malaria elimination gains.

PMID- 24886146
TI  - Hope and despair: community health assistants' experiences of working in a rural
      district in Zambia.
AB  - BACKGROUND: In order to address the challenges facing the community-based health
      workforce in Zambia, the Ministry of Health implemented the national community
      health assistant strategy in 2010. The strategy aims to address the challenges by
      creating a new group of workers called community health assistants (CHAs) and
      integrating them into the health system. The first group started working in
      August 2012. The objective of this paper is to document their motivation to
      become a CHA, their experiences of working in a rural district, and how these
      experiences affected their motivation to work. METHODS: A phenomenological
      approach was used to examine CHAs' experiences. Data collected through in-depth
      interviews with 12 CHAs in Kapiri Mposhi district and observations were analysed
      using a thematic analysis approach. RESULTS: Personal characteristics such as
      previous experience and knowledge, passion to serve the community and a desire to
      improve skills motivated people to become CHAs. Health systems characteristics
      such as an inclusive work culture in some health posts motivated CHAs to work.
      Conversely, a non-inclusive work culture created a social structure which
      constrained CHAs' ability to learn, to be innovative and to effectively conduct
      their duties. Further, limited supervision, misconceptions about CHA roles, poor
      prioritisation of CHA tasks by some supervisors, as well as non- and irregular
      payment of incentives also adversely affected CHAs' ability to work effectively.
      In addition, negative feedback from some colleagues at the health posts affected
      CHA's self-confidence and professional outlook. In the community, respect and
      support provided to CHAs by community members instilled a sense of recognition,
      appreciation and belonging in CHAs which inspired them to work. On the other
      hand, limited drug supplies and support from other community-based health workers
      due to their exclusion from the government payroll inhibited CHAs' ability to
      deliver services. CONCLUSIONS: Programmes aimed at integrating community-based
      health workers into health systems should adequately consider multiple
      incentives, effective management, supervision and support from the district.
      These should be tailored towards enhancing the individual, health system and
      community characteristics that positively impact work motivation at the local
      level if such programmes are to effectively contribute towards improved primary
      healthcare.

PMID- 24886147
TI  - The relationship between self-efficacy and anxiety and general distress in
      caregivers of people with advanced cancer.
AB  - BACKGROUND: Informal caregivers take on an important role in supporting people
      with advanced cancer but experience significant psychological distress.
      OBJECTIVE: This study aims to describe the prevalence of anxiety and distress in
      a sample of caregivers of people with advanced cancer and explore the
      relationship with self-efficacy. METHODS: A cross-sectional survey was used.
      Subjects were 94 caregivers of people with advanced cancer recruited from a
      specialist oncology setting. Questionnaires included the Caregiver Self-Efficacy
      Scale (CaSES), the State Trait Anxiety Inventory (STAI), and the Distress
      Thermometer. Demographic data were recorded. RESULTS: The sample consisted of 94
      caregivers of people with advanced cancer. The majority were female (66; 70.2%)
      with a mean age of 55 years. The mean distress score for the sample was 4.87
      (standard deviation [SD] 2.49). Fifty-five caregivers (59.1%) had a score of >=5
      on the Distress Thermometer indicating distress. The state anxiety mean was 45.21
      (SD 12.32) and trait anxiety mean was 41.21 (SD 10.143). Females had more
      distress and state anxiety than males. Only one self-efficacy scale, self
      maintenance, correlated with distress. All STAI scores correlated with self
      efficacy and self-maintenance had the strongest relationship. CONCLUSIONS:
      Caregivers had high anxiety and distress. Caregivers with higher anxiety reported
      lower self-efficacy. The strongest correlation was with the self-maintenance
      subscale, indicating an association with psychological functioning and caregivers
      who are able to access respite and take care of themselves during care provision.

PMID- 24886148
TI  - Transcriptome differences between two sister desert poplar species under salt
      stress.
AB  - BACKGROUND: Populus euphratica Oliv and P. pruinosa Schrenk (Salicaceae) both
      grow in dry desert areas with high summer temperatures. However, P. euphratica is
      distributed in dry deserts with deep underground water whereas P. pruinosa occurs
      in deserts in which there is underground water close to the surface. We therefore
      hypothesized that these two sister species may have evolved divergent regulatory
      and metabolic pathways during their interaction with different salt habitats and
      other stresses. To test this hypothesis, we compared transcriptomes from callus
      exposed to 24 h of salt stress and control callus samples from both species and
      identified differentially expressed genes (DEGs) and alternative splicing (AS)
      events that had occurred under salt stress. RESULTS: A total of 36,144
      transcripts were identified and 1430 genes were found to be differentially
      expressed in at least one species in response to salt stress. Of these DEGs, 884
      and 860 were identified in P. euphratica and P. pruinosa, respectively, while 314
      DEGs were common to both species. On the basis of parametric analysis of gene set
      enrichment, GO enrichment in P. euphratica was found to be significantly
      different from that in P. pruinosa. Numerous genes involved in hormone
      biosynthesis, transporters and transcription factors showed clear differences
      between the two species in response to salt stress. We also identified 26,560 AS
      events which were mapped to 8380 poplar genomic loci from four libraries. GO
      enrichments for genes undergoing AS events in P. euphratica differed
      significantly from those in P. pruinosa. CONCLUSIONS: A number of salt-responsive
      genes in both P. euphratica and P. pruinosa were identified and candidate genes
      with potential roles in the salinity adaptation were proposed. Transcriptome
      comparisons of two sister desert poplar species under salt stress suggest that
      these two species may have developed different genetic pathways in order to adapt
      to different desert salt habitats. The DEGs that were found to be common to both
      species under salt stress may be especially important for future genetic
      improvement of cultivated poplars or other crops through transgenic approaches in
      order to increase tolerance of saline soil conditions.

PMID- 24886149
TI  - Evaluation of the vitreous microbial contamination rate in office-based three
      port microincision vitrectomy surgery using Retrector technology.
AB  - BACKGROUND: To perform a microbiological contamination analysis of the vitreous
      during office-based micro-incision vitrectomy surgery (MIVS) assessing whether
      the bacteria detected correlated with patient's ocular conjunctival flora.
      METHODS: This is a prospective, interventional, nonrandomized case series of
      patients undergoing office-based MIVS, anti-VEGF, and dexamethasone intravitreal
      injections (triple therapy) for the treatment of wet age-related macular
      degeneration (AMD) and diabetic macular edema (DME).All patients were operated at
      a small procedure room in an ambulatory clinic of the Department of
      Ophthalmology, University of Montreal, Quebec, Canada. Conjunctival samples were
      done before placing the sclerotomies. The MIVS was done with a 23-gauge
      retractable vitrector, a 27-gauge infusion line, and a 29-gauge chandelier.
      Undiluted and diluted vitreous were collected for aerobic, anaerobic and fungal
      cultures. Outcomes measured were bacterial species identification within samples
      collected from the conjunctiva and the vitreous. RESULTS: Thirty-seven patients
      (37 eyes) were recruited and completed over 17 months of follow-up. Twenty-eight
      had wet AMD and nine had DME. There were 13 men and 24 women, with a mean age of
      78 years. Eighteen patients (46%) had culture positive conjunctival flora. Twenty
      six bacterial colonies were tabulated in total from the conjunctival swabs. All
      bacteria detected were gram-positive bacteria (100%), most commonly:
      Staphylococcus epidermitis in 11 (42%) and Corynebacterium sp. in 6 (23%). Only
      1/18 patients had more than 3 species isolated, 6/18 patients had 2 species and
      11/18 patients had 1 species identified on the conjunctival swab. Only 1 of the
      37 undiluted midvitreous samples was culture positive, equating to a
      contamination rate of 2.7%. None of the diluted vitreous samples were culture
      positive. All cultures were negative for fungus. No serious postoperative
      complications occurred, including bacterial endophthalmitis, choroidal
      detachment, and retinal detachment. CONCLUSION: This preliminary study of office
      based MIVS gives us insights on the ocular surface microbial profile and vitreous
      contamination rate of performing such procedures outside the OR-controlled
      environment. Our initial results seem to indicate that there is little risk of
      bacterial translocation and contamination from the conjunctiva into the vitreous.
      Therefore, if endophthalmitis occurs post-operatively, the source may likely
      arise after the procedure. Larger studies are needed to confirm our data.

PMID- 24886150
TI  - Metasecretome-selective phage display approach for mining the functional
      potential of a rumen microbial community.
AB  - BACKGROUND: In silico, secretome proteins can be predicted from completely
      sequenced genomes using various available algorithms that identify membrane
      targeting sequences. For metasecretome (collection of surface, secreted and
      transmembrane proteins from environmental microbial communities) this approach is
      impractical, considering that the metasecretome open reading frames (ORFs)
      comprise only 10% to 30% of total metagenome, and are poorly represented in the
      dataset due to overall low coverage of metagenomic gene pool, even in large-scale
      projects. RESULTS: By combining secretome-selective phage display and next
      generation sequencing, we focused the sequence analysis of complex rumen
      microbial community on the metasecretome component of the metagenome. This
      approach achieved high enrichment (29 fold) of secreted fibrolytic enzymes from
      the plant-adherent microbial community of the bovine rumen. In particular, we
      identified hundreds of heretofore rare modules belonging to cellulosomes, cell
      surface complexes specialised for recognition and degradation of the plant fibre.
      CONCLUSIONS: As a method, metasecretome phage display combined with next
      generation sequencing has a power to sample the diversity of low-abundance
      surface and secreted proteins that would otherwise require exceptionally large
      metagenomic sequencing projects. As a resource, metasecretome display library
      backed by the dataset obtained by next-generation sequencing is ready for i)
      affinity selection by standard phage display methodology and ii) easy
      purification of displayed proteins as part of the virion for individual
      functional analysis.

PMID- 24886152
TI  - Predicting the cumulative risk of death during hospitalization by modeling
      weekend, weekday and diurnal mortality risks.
AB  - BACKGROUND: Current prognostic models factor in patient and disease specific
      variables but do not consider cumulative risks of hospitalization over time. We
      developed risk models of the likelihood of death associated with cumulative
      exposure to hospitalization, based on time-varying risks of hospitalization over
      any given day, as well as day of the week. Model performance was evaluated alone,
      and in combination with simple disease-specific models. METHOD: Patients admitted
      between 2000 and 2006 from 501 public and private hospitals in NSW, Australia
      were used for training and 2007 data for evaluation. The impact of hospital care
      delivered over different days of the week and or times of the day was modeled by
      separating hospitalization risk into 21 separate time periods (morning, day,
      night across the days of the week). Three models were developed to predict death
      up to 7-days post-discharge: 1/a simple background risk model using age, gender;
      2/a time-varying risk model for exposure to hospitalization (admission time, days
      in hospital); 3/disease specific models (Charlson co-morbidity index, DRG).
      Combining these three generated a full model. Models were evaluated by accuracy,
      AUC, Akaike and Bayesian information criteria. RESULTS: There was a clear diurnal
      rhythm to hospital mortality in the data set, peaking in the evening, as well as
      the well-known 'weekend-effect' where mortality peaks with weekend admissions.
      Individual models had modest performance on the test data set (AUC 0.71, 0.79 and
      0.79 respectively). The combined model which included time-varying risk however
      yielded an average AUC of 0.92. This model performed best for stays up to 7-days
      (93% of admissions), peaking at days 3 to 5 (AUC 0.94). CONCLUSIONS: Risks of
      hospitalization vary not just with the day of the week but also time of the day,
      and can be used to make predictions about the cumulative risk of death associated
      with an individual's hospitalization. Combining disease specific models with such
      time varying- estimates appears to result in robust predictive performance. Such
      risk exposure models should find utility both in enhancing standard prognostic
      models as well as estimating the risk of continuation of hospitalization.

PMID- 24886151
TI  - Supported cognitive-behavioural self-help versus treatment-as-usual for depressed
      informal carers of stroke survivors (CEDArS): study protocol for a feasibility
      randomized controlled trial.
AB  - BACKGROUND: Increased life expectancy has resulted in a greater provision of
      informal care within the community for patients with chronic physical health
      conditions. Informal carers are at greater risk of poor mental health, with one
      in three informal carers of stroke survivors experiencing depression. However,
      currently no psychological treatments tailored to the unique needs of depressed
      informal carers of stroke survivors exist. Furthermore, informal carers of stroke
      survivors experience a number of barriers to attending traditional face-to-face
      psychological services, such as lack of time and the demands of the caring role.
      The increased flexibility associated with supported cognitive behavioral therapy
      self-help (CBTsh), such as the ability for support to be provided by telephone,
      email, or face-to-face, alongside shorter support sessions, may help overcome
      such barriers to access. CBTsh, tailored to depressed informal carers of stroke
      survivors may represent an effective and acceptable solution. METHODS/DESIGN:
      This study is a Phase II (feasibility) randomized controlled trial (RCT)
      following guidance in the MRC Complex Interventions Research Methods Framework.
      We will randomize a sample of depressed informal carers of stroke survivors to
      receive CBT self-help supported by mental health paraprofessionals, or treatment
      as-usual. Consistent with the objectives of assessing the feasibility of trial
      design and procedures for a potential larger scale trial we will measure the
      following outcomes: a) feasibility of patient recruitment (recruitment and
      refusal rates); (b) feasibility and acceptability of data collection procedures;
      (c) levels of attrition; (d) likely intervention effect size; (e) variability in
      number, length and frequency of support sessions estimated to bring about
      recovery; and (f) acceptability of the intervention. Additionally, we will
      collect data on the diagnosis of depression, symptoms of depression and anxiety,
      functional impairment, carer burden, quality of life, and stroke survivor
      mobility skill, self-care and functional ability, measured at four and six months
      post-randomization. DISCUSSION: This study will provide important information for
      the feasibility and design of a Phase III (effectiveness) trial in the future. If
      the intervention is identified to be feasible, effective, and acceptable, a
      written CBTsh intervention for informal carers of stroke survivors, supported by
      mental health paraprofessionals, could represent a cost-effective model of care.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN63590486.

PMID- 24886153
TI  - Seroepidemiology of Toxocara canis infection among primary schoolchildren in the
      capital area of the Republic of the Marshall Islands.
AB  - BACKGROUND: Toxocariasis, which is predominantly caused by Toxocara canis (T.
      canis) infection, is a common zoonotic parasitosis worldwide; however, the status
      of toxocariasis endemicity in the Republic of the Marshall Islands (RMI) remains
      unknown. METHODS: A seroepidemiological investigation was conducted among 166
      primary school children (PSC) aged 7-12 years from the capital area of the RMI.
      Western blots based the excretory-secretory antigens of larval T. canis (TcES)
      was employed, and children were considered seropositive if their serum reacted
      with TcES when diluted at a titer of 1:64. Information regarding demographic
      characteristics of and environmental risk factors affecting these children was
      collected using a structured questionnaire. A logistic regression model was
      applied to conduct a multivariate analysis. RESULTS: The overall seropositive
      rate of T. canis infection was 86.75% (144/166). In the univariate analysis, PSC
      who exhibited a history of feeding dogs at home (OR = 5.52, 95% CI = 1.15-26.61,
      p = 0.02) and whose parents were employed as nonskilled workers (OR = 2.86, 95%
      CI = 1.08-7.60, p = 0.03) demonstrated a statistically elevated risk of
      contracting T. canis infections. Cleaning dog huts with gloves might prevent
      infection, but yielded nonsignificant effects. The multivariate analysis
      indicated that parental occupation was the critical risk factor in this study
      because its effect remained significant after adjusting for other variables; by
      contrast, the effect of dog feeding became nonsignificant because of other
      potential confounding factors. No associations were observed among gender, age,
      consuming raw meat or vegetables, drinking unboiled water, cleaning dog huts with
      gloves, or touching soil. CONCLUSIONS: This is the first serological
      investigation of T. canis infection among PSC in the RMI. The high seroprevalence
      indicates the commonness of T. canis transmission and possible human risk. The
      fundamental information that the present study provides regarding T. canis
      epidemiology can facilitate developing strategies for disease prevention and
      control.

PMID- 24886154
TI  - Perceived competence and attitudes towards patients with suicidal behaviour: a
      survey of general practitioners, psychiatrists and internists.
AB  - BACKGROUND: Competence and attitudes to suicidal behaviour among physicians are
      important to provide high-quality care for a large patient group. The aim was to
      study different physicians' attitudes towards suicidal behaviour and their
      perceived competence to care for suicidal patients. METHODS: A random selection
      (n = 750) of all registered General Practitioners, Psychiatrists and Internists
      in Norway received a questionnaire. The response rate was 40%. The Understanding
      of Suicidal Patients Scale (USP; scores < 23 = positive attitude) and items about
      suicide in case of incurable illness from the Attitudes Towards Suicide
      Questionnaire were used. Five-point Likert scales were used to measure self
      perceived competence, level of commitment, empathy and irritation felt towards
      patients with somatic and psychiatric diagnoses. Questions about training were
      included. RESULTS: The physicians held positive attitudes towards suicide
      attempters (USP = 20.3, 95% CI: 19.6-20.9). Internists and males were
      significantly less positive. There were no significant differences in the
      physicians in their attitudes toward suicide in case of incurable illness
      according to specialty. The physicians were most irritated and less committed to
      substance misuse patients. Self perceived competence was relatively high. Forty
      three percent had participated in courses about suicide assessment and treatment.
      CONCLUSIONS: The physicians reported positive attitudes and relatively high
      competence. They were least committed to treat patients with substance misuse.
      None of the professional groups thought that patients with incurable illness
      should be given help to commit suicide. Further customized education with focus
      on substance misuse might be useful.

PMID- 24886156
TI  - "I eat the manofe so it is not forgotten": local perceptions and consumption of
      native wild edible plants from seasonal dry forests in Brazil.
AB  - BACKGROUND: There is little information available on the factors influencing
      people's selection of wild plants for consumption. Studies suggest a suitable
      method of understanding the selection of edible plants is to assess people's
      perceptions of these resources. The use and knowledge of wild resources is
      disappearing, as is the opportunity to use them. This study analyzes people's
      perceptions of native wild edible plants in a rural Caatinga (seasonal dry
      forest) community in Northeast Brazil and the relationships between the use of
      these resources and socioeconomic factors. METHODS: Semi-structured interviews
      with 39 people were conducted to form a convenience sample to gather information
      regarding people's perceptions of 12 native wild edible plant species. The
      relationships between variables were assessed by simple linear regression
      analysis, Pearson and Spearman correlation analyses, and in the case of nominal
      variables, contingency tables. The discourse of participants regarding their
      opinions of the use of wild plants as food was analyzed through the collective
      subject discourse analysis technique. RESULTS: Perceptions were classified into
      18 categories. The most cited category was organoleptic characteristics of the
      edible part; more specifically, flavor. Flavor was the main positive perception
      associated with plant use, whereas the negative perception that most limited the
      use of these plants was cultural acceptance. Perceptions of the use of wild
      edible plants were directly correlated with both interviewee age and income.
      CONCLUSION: Within the studied community, people's perceptions of native wild
      edible plants are related to their consumption. Moreover, the study found that
      young people have less interest in these resources. These findings suggest that
      changing perceptions may affect the conservation of plants, traditional practices
      and the associated knowledge.

PMID- 24886155
TI  - Oxidative-stress induced increase in circulating fatty acids does not contribute
      to phospholipase A2-dependent appetitive long-term memory failure in the pond
      snail Lymnaea stagnalis.
AB  - BACKGROUND: Reactive oxygen species (ROS) are essential for normal physiological
      functioning of the brain. However, uncompensated increase in ROS levels may
      results in oxidative stress. Phospholipase A2 (PLA2) is one of the key players
      activated by elevated ROS levels resulting in the hydrolysis of various products
      from the plasmamembrane such as peroxidized fatty acids. Free fatty acids (FFAs)
      and fatty acid metabolites are often implicated to the genesis of cognitive
      impairment. Previously we have shown that age-, and experimentally induced
      oxidative stress causes PLA2-dependent long-term memory (LTM) failure in an
      aversive operant conditioning model in Lymnaea stagnalis. In the present study,
      we investigate the effects of experimentally induced oxidative stress and the
      role of elevated levels of circulating FFAs on LTM function using a non-aversive
      appetitive classical conditioning paradigm. RESULTS: We show that intracoelomic
      injection of exogenous PLA2 or pro-oxidant induced PLA2 activation negatively
      affects LTM performance in our learning paradigm. In addition, we show that
      experimental induction of oxidative stress causes significant temporal changes in
      circulating FFA levels. Importantly, the time of training coincides with the peak
      of this change in lipid metabolism. However, intracoelomic injection with
      exogenous arachidonic acid, one of the main FFAs released by PLA2, does not
      affect LTM function. Moreover, sequestrating circulating FFAs with the aid of
      bovine serum albumin does not rescue pro-oxidant induced appetitive LTM failure.
      CONCLUSIONS: Our data substantiates previous evidence linking lipid peroxidation
      and PLA2 activation to age- and oxidative stress-related cognitive impairment,
      neuronal dysfunction and disease. In addition however, our data indicate that
      lipid peroxidation induced increased levels of circulating (per)oxidized FFAs are
      not a factor in oxidative stress induced LTM impairment.

PMID- 24886158
TI  - The relationship between alcohol cues, alcohol expectancies, and physical
      balance.
AB  - Although previous research has shown that beliefs about alcohol (expectancies)
      are associated with alcohol-consistent, nonconsumptive behavior (e.g.,
      aggression; Friedman, McCarthy, Bartholow, & Hicks, 2007), no research has
      examined the effects of such expectancy on physical balance. The purpose of the
      current research was to test the association between alcohol cue exposure and
      feelings of imbalance. Study 1 showed that participants exhibited poorer balance
      in the presence of alcohol-related pictures compared to neutral (e.g., juice) or
      no pictures. Study 2 found that people exhibited a heightened accessibility of
      alcohol-related thoughts following a manipulation where they felt imbalanced
      (i.e., rocking on a wobble board) versus balanced. Study 3 showed that people
      with higher positive expectancies about alcohol reported a greater number of
      alcohol-related thoughts after they were made to feel imbalanced (vs. balanced).
      Implications of this research for alcohol expectancies, embodied cognition, and
      psychomotor functioning are further discussed.

PMID- 24886157
TI  - Drug specificity in drug versus food choice in male rats.
AB  - Although different classes of drug differ in their mechanisms of reinforcement
      and effects on behavior, little research has focused on differences in self
      administration behaviors maintained by users of these drugs. Persistent drug
      choice despite available reinforcement alternatives has been proposed to model
      behavior relevant to addiction. The present study used a within-subjects
      procedure, where male rats (Long-Evans, N = 16) were given a choice between
      cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between
      heroin (0.02 mg/kg/infusion) and food in separate phases (drug order
      counterbalanced). All rats were initially trained to self-administer each drug,
      and the doses used were based on previous studies showing that small subsets of
      rats tend to prefer drug over food reinforcement. The goal of the present study
      was to determine whether rats that prefer cocaine would also prefer heroin.
      Choice sessions consisted of 2 forced-choice trials with each reinforcer,
      followed by 14 free-choice trials (all trials separated by 10-min intertrial
      interval). Replicating previous results, small subsets of rats preferred either
      cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative.
      Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin
      to the food alternative, there was no relationship between degree of cocaine and
      heroin preference in individual rats. The substance-specific pattern of drug
      preference observed suggests that at least in this animal model, the tendencies
      to prefer cocaine or heroin in preference to a nondrug alternative are distinct
      behavioral phenomena.

PMID- 24886159
TI  - Interventions to improve delivery of isoniazid preventive therapy: an overview of
      systematic reviews.
AB  - BACKGROUND: Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis
      has been poor, particularly in the highest risk populations. Interventions to
      improve IPT delivery could promote implementation. The large number of existing
      systematic reviews on treatment adherence has made drawing conclusions a
      challenge. To provide decision makers with the evidence they need, we performed
      an overview of systematic reviews to compare different organizational
      interventions to improve IPT delivery as measured by treatment completion among
      those at highest risk for the development of TB disease, namely child contacts or
      HIV-infected individuals. METHODS: We searched the Cochrane Database of
      Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), and
      MEDLINE up to August 15, 2012. Two authors used a standardized data extraction
      form and the AMSTAR instrument to independently assess each review. RESULTS: Six
      reviews met inclusion criteria. Interventions included changes in the
      setting/site of IPT delivery, use of quality monitoring mechanisms (e.g.,
      directly observed therapy), IPT delivery integration into other healthcare
      services, and use of lay health workers. Most reviews reported a combination of
      outcomes related to IPT adherence and treatment completion rate but without a
      baseline or comparison rate. Generally, we found limited evidence to demonstrate
      that the studied interventions improved treatment completion. CONCLUSIONS: While
      most of the interventions were not shown to improve IPT completion, integration
      of tuberculosis and HIV services yielded high treatment completion rates in some
      settings. The lack of data from high burden TB settings limits applicability.
      Further research to assess different IPT delivery interventions, including those
      that address barriers to care in at-risk populations, is urgently needed to
      identify the most effective practices for IPT delivery and TB control in high TB
      burden settings.

PMID- 24886161
TI  - Indoleamine 2,3-dioxygenase (IDO) is frequently expressed in stromal cells of
      Hodgkin lymphoma and is associated with adverse clinical features: a
      retrospective cohort study.
AB  - BACKGROUND: Regulation of tumor microenvironment is closely involved in the
      prognosis of Hodgkin lymphoma (HL). Indoleamine 2,3-dioxygenase (IDO) is an
      enzyme acting as immune modulator through suppression of T-cell immunity. This
      study aims to investigate role of IDO in the microenvironment of HL. METHODS: A
      total of 121 cases of HL were enrolled to do immunohistochemistry for IDO, CD163,
      CD68, CD4, CD8, and FoxP3. Positivity was evaluated from area fractions or
      numbers of positive cells using automated image analyzer. Correlations between
      IDO expression and various cellular infiltrates and clinicopathologic parameters
      were examined and survival analyses were performed. RESULTS: IDO was expressed in
      histiocytes, dendritic cells and some endothelial cells with variable degrees,
      but not in tumor cells. IDO positive cells were more frequently found in mixed
      cellularity type than other histologic types, and in cases with EBV+, high Ann
      Arbor stages, B symptoms, and high IPS (all p < 0.05). High IDO expression was
      associated with inferior survival (p < 0.001) and reflects an independent
      prognostic factor in nodular sclerosis HL. CONCLUSIONS: This is the first study
      suggesting that IDO is the principle immunomodulator and is involved to adverse
      clinical outcomes of HL.

PMID- 24886160
TI  - The midgut of Aedes albopictus females expresses active trypsin-like serine
      peptidases.
AB  - BACKGROUND: Aedes albopictus is widely distributed across tropical and sub
      tropical regions and is associated with the transmission of several arboviruses.
      Although this species is increasingly relevant to public health due its ability
      to successfully colonize both urban and rural habitats, favoring the dispersion
      of viral infections, little is known about its biochemical traits, with all
      assumptions made based on studies of A. aegypti. In previous studies we
      characterized the peptidase profile of pre-imaginal stages of A. albopictus and
      we reported the first proteomic analysis of the midgut from sugar-fed females of
      this insect species. METHODS: In the present work, we further analyzed the
      peptidase expression in the midgut of sugar-fed females using 1DE-substrate gel
      zymography, two-dimensional electrophoresis (2DE), mass spectrometry (MS), and
      protein identification based on similarity. RESULTS: The combination of
      zymography, in solution assays using fluorescent substrates and 2DE-MS/MS allowed
      us to identify the active serine peptidase "fingerprint" in the midgut of A.
      albopictus females. Zymographic analysis revealed a proteolytic profile composed
      of at least 13 bands ranging from ~25 to 250 kDa, which were identified as
      trypsin-like serine peptidases by using specific inhibitors of this class of
      enzymes. Concomitant use of the fluorogenic substrate Z-Phe-Arg-AMC and trypsin
      like serine protease inhibitors corroborated the zymographic findings. Our
      proteomic approach allowed the identification of two different trypsin-like
      serine peptidases and one chymotrypsin in protein spots of the alkaline region in
      2DE map of the A. albopictus female midgut. Identification of these protein
      coding genes was achieved by similarity to the A. aegypti genome sequences using
      Mascot and OMSSA search engines. CONCLUSION: These results allowed us to detect,
      identify and characterize the expression of active trypsin-like serine peptidases
      in the midgut of sugar-fed A. albopictus females. In addition, proteomic analysis
      allowed us to confidently assign the expression of two trypsin genes and one
      chymotrypsin gene to the midgut of this mosquito. These results contribute to the
      gene annotation in this species of unknown genome and represent a small but
      important step toward the protein-level functional and localization assignment of
      trypsin-like serine peptidase genes in the Aedes genus.

PMID- 24886162
TI  - Children and adolescents adjustment to parental multiple sclerosis: a systematic
      review.
AB  - BACKGROUND: Families are the primary source of support and care for most
      children. In Western societies, 4 to 12% of children live in households where a
      parent has a chronic illness. Exposure to early-life stressors, including
      parenting stress, parental depression and parental chronic disease could lead to
      harmful changes in children's social, emotional or behavioural functioning.
      Little is known about the child living with a parent who has Multiple Sclerosis
      (MS). We systematically reviewed the literature regarding possible effects of
      having a parent with MS on the child's or adolescent's psychosocial adjustment.
      METHODS: The following databases: MEDLINE, PsychInfo, CINAHL, EMBASE, Web of
      Knowledge, ERIC, and ProQuest Digital Dissertations were searched (from 1806 to
      December 2012). References from relevant articles were also manually searched.
      Selected studies were evaluated using the Graphic Appraisal Tool for Epidemiology
      (GATE). RESULTS: The search yielded 3133 titles; 70 articles were selected for
      full text review. Eighteen studies met inclusion criteria. Fourteen studies
      employed quantitative techniques, of which 13 were cross-sectional and one was
      longitudinal. Four studies were both qualitative and cross-sectional in design.
      Only 2 of 18 studies were rated as having high methodological quality. Overall,
      eight studies reported that children of MS patients exhibited negative
      psychosocial traits compared with children of "healthy" parents. Specifically for
      adolescents, greater family responsibilities were linked to lower social
      relationships and higher distress. Three studies indicated that parental MS was
      associated with positive adjustment in children and adolescents, such as higher
      personal competence, while four found no statistically significant differences.
      CONCLUSION: Although having a parent with MS was often reported to have negative
      psychosocial effects on children and adolescents, there was a lack of consensus
      and some positive aspects were also found. However, few high quality studies were
      identified which makes it difficult to draw evidence-based conclusions at this
      point. There are potentially important, long-term impacts of early life
      stressors, such as having a parent with a chronic disease, on subsequent life
      chances and health, and thus more extensive and higher quality research in this
      area is greatly needed.

PMID- 24886163
TI  - Risk of secondary cancers from scattered radiation during intensity-modulated
      radiotherapies for hepatocellular carcinoma.
AB  - PURPOSE: To evaluate and compare the risks of secondary cancers from therapeutic
      doses received by patients with hepatocellular carcinoma (HCC) during intensity
      modulated radiotherapy (IMRT), volumetric arc therapy (VMAT), and tomotherapy
      (TOMO). METHODS: Treatments for five patients with hepatocellular carcinoma (HCC)
      were planned using IMRT, VMAT, and TOMO. Based on the Biological Effects of
      Ionizing Radiation VII method, the excess relative risk (ERR), excess absolute
      risk (EAR), and lifetime attributable risk (LAR) were evaluated from therapeutic
      doses, which were measured using radiophotoluminescence glass dosimeters (RPLGDs)
      for each organ inside a humanoid phantom. RESULTS: The average organ equivalent
      doses (OEDs) of 5 patients were measured as 0.23, 1.18, 0.91, 0.95, 0.97, 0.24,
      and 0.20 Gy for the thyroid, lung, stomach, liver, small intestine, prostate (or
      ovary), and rectum, respectively. From the OED measurements, LAR incidence were
      calculated as 83, 46, 22, 30, 2 and 6 per 10(4) person for the lung, stomach,
      normal liver, small intestine, prostate (or ovary), and rectum. CONCLUSIONS: We
      estimated the secondary cancer risks at various organs for patients with HCC who
      received different treatment modalities. We found that HCC treatment is
      associated with a high secondary cancer risk in the lung and stomach.

PMID- 24886164
TI  - What have we learned from cancer immunotherapy in the last 3 years?
AB  - Until recently, most immunotherapeutic approaches used to fight cancer were
      ineffective, counteracted by the tumour's ability to evade immune attack.
      However, extensive research has improved our understanding of tumour immunology
      and enabled the development of novel treatments that can harness the patient's
      immune system and prevent immune escape. Over the last few years, through
      numerous clinical trials and real-world experience, we have accumulated a large
      amount of evidence regarding the potential for long-term survival with
      immunotherapy agents in various types of malignancy. The results of these studies
      have also highlighted a number of recurring observations with immuno-oncology
      agents, including their potential for clinical application across a broad patient
      population and for both conventional and unconventional response patterns.
      Furthermore, given the numerous immune checkpoints that exist and the multiple
      mechanisms used by tumours to escape the immune system, targeting distinct
      checkpoint pathways using combination approaches is an attractive therapeutic
      strategy with the potential to further enhance the antitumour immune response. 

PMID- 24886165
TI  - Translation, cultural adaptation and field-testing of the Thinking Healthy
      Program for Vietnam.
AB  - BACKGROUND: Depression and anxiety are prevalent among women in low- and lower
      middle income countries who are pregnant or have recently given birth. There is
      promising evidence that culturally-adapted, evidence-informed, perinatal psycho
      educational programs implemented in local communities are effective in reducing
      mental health problems. The Thinking Healthy Program (THP) has proved effective
      in Pakistan. The aims were to adapt the THP for rural Vietnam; establish the
      program's comprehensibility, acceptability and salience for universal use, and
      investigate whether administration to small groups of women might be of
      equivalent effectiveness to administration in home visits to individual women.
      METHODS: The THP Handbook and Calendar were made available in English by the
      program developers and translated into Vietnamese. Cultural adaptation and field
      testing were undertaken using WHO guidance. Field-testing of the four sessions of
      THP Module One was undertaken in weekly sessions with a small group in a rural
      commune and evaluated using baseline, process and endline surveys. RESULTS: The
      adapted Vietnamese version of the Thinking Healthy Program (THP-V) was found to
      be understandable, meaningful and relevant to pregnant women, and commune health
      centre and Women's Union representatives in a rural district. It was delivered
      effectively by trained local facilitators. Role-play, brainstorming and small
      group discussions to find shared solutions to common problems were appraised as
      helpful learning opportunities. CONCLUSIONS: The THP-V is safe and
      comprehensible, acceptable and salient to pregnant women without mental health
      problems in rural Vietnam. Delivery in facilitated small groups provided valued
      opportunities for role-play rehearsal and shared problem solving. Local observers
      found the content and approach highly relevant to local needs and endorsed the
      approach as a mental health promotion strategy with potential for integration
      into local universal maternal and child health services. These preliminary data
      indicate that the impact of the THP-V should be tested in its complete form in a
      large scale trial.

PMID- 24886166
TI  - Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses
      vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer
      PaTu8988 cells.
AB  - BACKGROUND: Pancreatic cancer is one of the most aggressive human malignancies
      with a extremely low 5-year survival rate. Hence, the search for more effective
      anti-pancreatic cancer agents is urgent. METHODS: PaTu8988 pancreatic cancer
      cells were treated with different concentrations of suberoylanilide hydroxamic
      acid (SAHA), cell survival, proliferation, migration and vasculogenic mimicry
      (VM) were analyzed. Associated signaling changes were also analyzed by RT-PCR and
      Western blots. RESULTS: Here, we reported that SAHA, a histone deacetylase
      inhibitor (HDACi), exerted significant inhibitory efficiency against pancreatic
      cancer cell survival, proliferation, migration and VM. SAHA dose-dependently
      inhibited PaTu8988 pancreatic cancer cell growth with the IC-50 of 3.4 +/- 0. 7
      MUM. Meanwhile, SAHA suppressed PaTu8988 cell cycle progression through inducing
      G2/M arrest, which was associated with cyclin-dependent kinase 1 (CDK-1)/cyclin
      B1 degradation and p21/p27 upregulation. Further, SAHA induced both apoptotic and
      non-apoptotic death of PaTu8988 cells. Significantly, SAHA suppressed PaTu8988
      cell in vitro migration and cell-dominant tube formation or VM, which was
      accompanied by semaphorin-4D (Sema-4D) and integrin-beta5 down-regulation. Our
      evidences showed that Akt activation might be important for Sema-4D expression in
      PaTu8988 cells, and SAHA-induced Sema-4D down-regulation might be associated with
      Akt inhibition. CONCLUSIONS: This study is among the first to report the VM
      formation in cultured human pancreatic cancer cells. And we provided strong
      evidence to suggest that SAHA executes significant anti-VM efficiency in the
      progressive pancreatic cancer cells. Thus, SAHA could be further investigated as
      a promising anti-pancreatic cancer agent.

PMID- 24886167
TI  - Safe performance of magnetic resonance of the heart in patients with magnetic
      resonance conditional pacemaker systems: the safety issue of the ESTIMATE study.
AB  - BACKGROUND: No published data exist about the safety of diagnostic magnetic
      resonance (MR) of the heart performed in a larger series of patients implanted
      with MR conditional pacemakers (PM). The purpose of our study is to analyse
      safety and potential alterations of electrical lead parameters in patients
      implanted with the EnRhythm/Advisa MRI SureScan PM with 5086MRI leads (Medtronic
      Inc.) during and after MR of the heart at 1.5 Tesla. METHODS: Patients enrolled
      in this single center pilot study who underwent non-clinically indicated
      diagnostic MR of the heart were included in this analysis. Heart MR was performed
      for analyses of potential changes in right and left ventricular functional
      parameters under right ventricular pacing at 80 and 110 bpm. Atrial/ventricular
      sensing, atrial/ventricular pacing capture threshold [PCT], and pacing impedances
      were assessed immediately before, during, and immediately after MR, as well at 3
      and 15 months post MR. RESULTS: Thirty-six patients (mean age 69 +/- 13 years;
      high degree AV block 18 [50%]) underwent MR of the heart. No MR related adverse
      events occurred during MR or thereafter. Ventricular sensing differed
      significantly between the FU immediately after MR (10.3 +/- 5.3 mV) and the
      baseline FU (9.8 +/- 5.3 mV; p < 0.05). Despite PCT [V/0.4ms] was not
      significantly different between the FUs (baseline: 0.84 +/- 0.27; in-between MR
      scans: 0.82 +/- 0.27; immediately after MR: 0.84 +/- 0.24; 3-month: 0.85 +/-
      0.23; 15-month: 0.90 +/- 0.67; p = ns), 7 patients (19%) showed PCT increases by
      100% (max. PCT measured: 1.0 V) at the 3-month FU compared to baseline. RV pacing
      impedance [Omega/5V] differed significantly at the FU in-between MR scans (516 +/
      47), and at the 15-month FU (482 +/- 58) compared to baseline (508 +/- 75).
      CONCLUSION: The results of our study suggest MR of the heart to be safe in
      patients with the MR conditional EnRhythm/Advisa system, albeit although
      noticeable but clinically irrelevant ventricular PCT changes were observed.

PMID- 24886168
TI  - Comparison of calculated and experimental power in maximal lactate-steady state
      during cycling.
AB  - BACKGROUND: The purpose of this study was the comparison of the calculated
      (MLSSC) and experimental power (MLSSE) in maximal lactate steady-state (MLSS)
      during cycling. METHODS: 13 male subjects (24.2 +/- 4.76 years, 72.9 +/- 6.9 kg,
      178.5 +/- 5.9 cm, VO2max: 60.4 +/- 8.6 ml min-1 kg-1, VLamax: 0.9 +/- 0.19 mmol l
      1 s-1) performed a ramp-test for determining the VO2max and a 15 s sprint-test
      for measuring the maximal glycolytic rate (VLamax). All tests were performed on a
      Lode-Cycle-Ergometer. VO2max and VLamax were used to calculate MLSSC. For the
      determination of MLSSE several 30 min constant load tests were performed. MLSSE
      was defined as the highest workload that can be maintained without an increase of
      blood-lactate-concentration (BLC) of more than 0.05 mmol l-1 min-1 during the
      last 20 min. Power in following constant-load test was set higher or lower
      depending on BLC. RESULTS: MLSSE and MLSSC were measured respectively at 217 +/-
      51 W and 229 +/- 47 W, while mean difference was -12 +/- 20 W. Orthogonal
      regression was calculated with r = 0.92 (p < 0.001). CONCLUSIONS: The difference
      of 12 W can be explained by the biological variability of VO2max and VLamax. The
      knowledge of both parameters, as well as their individual influence on MLSS,
      could be important for establishing training recommendations, which could lead to
      either an improvement in VO2max or VLamax by performing high intensity or low
      intensity exercise training, respectively. Furthermore the validity of VLamax 
      test should be focused in further studies.

PMID- 24886169
TI  - The importance of dietary change for men diagnosed with and at risk of prostate
      cancer: a multi-centre interview study with men, their partners and health
      professionals.
AB  - BACKGROUND: The diagnosis of prostate cancer (PC) can provide a trigger for
      dietary change, and there is evidence that healthier diets may improve quality of
      life and clinical outcomes. However, men's views about dietary change in PC
      survivorship are largely unknown. This multi-centre qualitative interview study
      explored men's views about dietary change in PC survivorship, to better
      understand motivations for, and barriers to, achieving desired changes. The role
      of radical and active surveillance treatments on dietary change and the influence
      of men's partners were examined. Focus groups also evaluated stakeholder opinion,
      including healthcare professionals, about the provision of dietary advice to PC
      patients. METHODS: A multi-centre interview study explored views about diet and
      motivations for, and barriers to, dietary change in men at elevated risk or
      diagnosed with PC following prostate specific antigen (PSA) testing. 58 men and
      11 partners were interviewed. Interviews and focus groups were undertaken with 11
      healthcare professionals, 5 patients and 4 partners to evaluate stakeholders'
      opinions about the feasibility and acceptability of providing dietary advice to
      PC patients. Data were analysed using methods of constant comparison and thematic
      analysis. RESULTS: Over half of diagnosed men reported making dietary changes,
      primarily to promote general or prostate health or facilitate coping, despite
      their uncertainty about diet-PC links. Interest in dietary advice was high.
      Information needs varied depending on treatment received, with men on active
      surveillance more frequently modifying their diet and regarding this as an
      adjunct therapy. Men considered their partners integral to implementing changes.
      Provision of dietary advice to men diagnosed with PC was considered by healthcare
      professionals and men to be feasible and appropriate in the context of a holistic
      'care package'. CONCLUSIONS: Many men make positive dietary changes after PC
      diagnosis, which are perceived by men and their partners to bring psychological
      and general health benefits and could help future dietary intervention trials.
      Men and their partners desire more and better dietary information that may
      support PC survivorship, particularly among those embarking on active
      surveillance/monitoring programmes. There are opportunities for healthcare
      professionals to support PC patients both clinically and psychologically by the
      routine integration of healthy eating advice into survivorship care plans.

PMID- 24886170
TI  - Mistaken identity? Visual similarities of marine debris to natural prey items of
      sea turtles.
AB  - BACKGROUND: There are two predominant hypotheses as to why animals ingest
      plastic: 1) they are opportunistic feeders, eating plastic when they encounter
      it, and 2) they eat plastic because it resembles prey items. To assess which
      hypothesis is most likely, we created a model sea turtle visual system and used
      it to analyse debris samples from beach surveys and from necropsied turtles. We
      investigated colour, contrast, and luminance of the debris items as they would
      appear to the turtle. We also incorporated measures of texture and translucency
      to determine which of the two hypotheses is more plausible as a driver of
      selectivity in green sea turtles. RESULTS: Turtles preferred more flexible and
      translucent items to what was available in the environment, lending support to
      the hypothesis that they prefer debris that resembles prey, particularly
      jellyfish. They also ate fewer blue items, suggesting that such items may be less
      conspicuous against the background of open water where they forage. CONCLUSIONS:
      Using visual modelling we determined the characteristics that drive ingestion of
      marine debris by sea turtles, from the point of view of the turtles themselves.
      This technique can be utilized to determine debris preferences of other visual
      predators, and help to more effectively focus management or remediation actions.

PMID- 24886172
TI  - Reactions of (+)-catechin with salivary nitrite and thiocyanate under conditions
      simulating the gastric lumen: production of dinitrosocatechin and its thiocyanate
      conjugate.
AB  - Catechins are ingested as food components and supplements. It is known that
      catechins are transformed to dinitrosocatechins by nitrite under acidic
      conditions, suggesting the possibility of their formation in the stomach because
      saliva contains nitrite. This paper deals with nitrite-induced transformation of
      (+)-catechin in methanol extracts of adzuki bean into 6,8-dinitrosocatechin in
      acidified saliva (pH ~ 1.9). As the mechanism of its formation, addition of
      nitric oxide (NO) to (+)-catechin semiquinone radical, both of which were
      produced in nitrous acid/(+)-catechin systems, was proposed. The
      dinitrosocatechin was oxidized to the quinone by nitrous acid, and the quinone
      reacted with a salivary component thiocyanate producing 6'-thiocyanato-6,8
      dinitrosocatechin. Since quinones are toxic, we propose a function of thiocyanate
      as a scavenger of the o-quinone formed from dinitrosocatechins in the stomach.

PMID- 24886171
TI  - Anaesthesia in patients undergoing cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy: retrospective analysis of a single centre three
      year experience.
AB  - BACKGROUND: Cytoreductive surgery combined with hyperthermic intraperitoneal
      chemotherapy (CRS/HIPEC) is a treatment option for selected patients with
      peritoneal carcinomatosis. There are limited data available on anaesthesia
      management and its impact on patients' outcome. Our aim was to retrospectively
      analyze and evaluate perioperative management and the clinical course of patients
      undergoing CRS/HIPEC within a three-year period. METHODS: After ethic committee
      approval, patient charts were retrospectively reviewed for patient
      characteristics, interventions, perioperative management, postoperative course,
      and complications. Analysis was intervention based. Data are presented as median
      (range). RESULTS: Between 2009 and 2011, 54 consecutive patients underwent 57
      interventions; median anaesthesia time was 715 (range 370 to 1135) minutes. HIPEC
      induced hyperthermia with an overall median peak temperature of 38.1 (35.7-40.2)
      degrees C with active cooling. Bleeding, expressed as median blood loss was 0.8
      (0 to 6) litre and large fluid shifts occurred, requiring a total fluid input of
      8.4 (4.2 to 29.4) litres per patient. Postoperative renal function was dependent
      on preoperative function and the type of fluids used. Administration of
      hydroxyethyl starch colloid solution had a significant negative impact on renal
      function, especially in younger patients. Major complications occurred after 12
      procedures leading to death in 2 patients. Procedure time and need for blood
      transfusion were associated with a significantly higher risk for major
      complications. CONCLUSIONS: Cytoreductive surgery with HIPEC is a high-risk
      surgical procedure associated with major hemodynamic and metabolic changes. As
      well as primary disease and complexity of surgery, we have shown that anaesthesia
      management, the type and amount of fluids used, and blood transfusions may also
      have a significant effect on patients' outcome.

PMID- 24886173
TI  - The value of Apolipoprotein B/Apolipoprotein A1 ratio for metabolic syndrome
      diagnosis in a Chinese population: a cross-sectional study.
AB  - BACKGROUND: The apoB/apoA1 ratio has been reported to be associated with the
      metabolic syndrome (MetS), and it may be a more convenient biomarker in MetS
      predicting. However, whether apoB/apoA1 ratio is a better indicator of metabolic
      syndrome than other biomarkers and what is the optimal cut-off value of
      apoB/apoA1 ratio as an indicator of metabolic syndrome in Chinese population
      remain unknown. Thus, we carried out the current study to assess the predictive
      value of apoB/apoA1 ratio and determine the optimal cut-off value of apoB/apoA1
      ratio for diagnosing MetS in a Chinese population. METHOD: We selected 1,855
      subjects with MetS and 6,265 individuals without MetS based on the inclusion and
      exclusion criteria from the China Health Nutrition Survey (CHNS) in 2009. MetS
      was identified based on the diagnostic criteria of International Diabetes
      Federation (2005). Logistic regression was used to estimate the association
      between the apoB/apoA1 ratio and risk of MetS, and receiver operating
      characteristics (ROC) curve analysis was performed to test the predictive value
      of apoB/apoA1 ratio and calculate the appropriate cut-off value. RESULTS:
      Compared with the lowest quartile of apoB/apoA1 ratio, subjects in the fourth
      quartile had a higher risk of MetS in both men [odds ratio (OR) = 2.64, 95%
      confidence interval (CI) =1.82-3.83] and women (OR = 5.18, 95% CI = 3.87-6.92)
      after adjustment for potential confounders. The optimal cut-off value of
      apoB/apoA1 ratio for MetS detection was 0.85 in men and 0.80 in women.
      Comparisons of ROC curves indicated that apoB/apoA1 ratio was better than
      traditional biomarkers in predicting MetS. CONCLUSION: Our results suggest that,
      apoB/apoA1 ratio has a promising predictive effectiveness in detection of MetS.
      An apoB/apoA1 ratio higher than 0.85 in men and 0.80 in women may be a promising
      and convenient marker of MetS.

PMID- 24886174
TI  - Recognizing Diogenes syndrome: a case report.
AB  - BACKGROUND: Diogenes syndrome is a behavioural disorder characterized by domestic
      squalor, extreme self-neglect, hoarding, and lack of shame regarding one's living
      condition. Patients may present due to a range of reasons. Recognizing these will
      allow for earlier management of this high-mortality condition. CASE PRESENTATION:
      61-year Caucasian female known with bipolar 1 disorder presented with manic
      symptoms. She was very unkempt and foul smelling. After being admitted
      involuntarily, she requested that someone go to her home to feed her pets. Her
      house was filled with garbage, rotting food, and animal feces. She had no insight
      into any personal hygiene or public health problems. CONCLUSIONS: Patients with
      Diogenes syndrome may be difficult to identify. Knowledge of the characteristics
      of Diogenes syndrome can aid in earlier recognition of such individuals, in order
      to decrease morbidity and mortality, and to improve public health.

PMID- 24886175
TI  - Exaggerated effects of particulate matter air pollution in genetic type II
      diabetes mellitus.
AB  - BACKGROUND: Prior experimental and epidemiologic data support a link between
      exposure to fine ambient particulate matter (<2.5 MUm in aerodynamic diameter,
      PM2.5) and development of insulin resistance/Type II diabetes mellitus. This
      study was designed to investigate whether inhalational exposure of concentrated
      PM2.5 in a genetically susceptible animal model would result in abnormalities in
      energy metabolism and exacerbation of peripheral glycemic control. METHODS: KKay
      mice, which are susceptible to Type II DM, were assigned to either concentrated
      ambient PM2.5 or filtered air (FA) for 5-8 weeks via a whole body exposure
      system. Glucose tolerance, insulin sensitivity, oxygen consumption and heat
      production were evaluated. At euthanasia, blood, spleen and visceral adipose
      tissue were collected to measure inflammatory cells using flow cytometry.
      Standard immnunohistochemical methods, western blotting and quantitative PCR were
      used to assess targets of interest. RESULTS: PM2.5 exposure influenced energy
      metabolism including O2 consumption, CO2 production, respiratory exchange ratio
      and thermogenesis. These changes were accompanied by worsened insulin resistance,
      visceral adiposity and inflammation in spleen and visceral adipose depots. Plasma
      adiponectin were decreased in response to PM2.5 exposure while leptin levels
      increased. PM2.5 exposure resulted in a significant increase in expression of
      inflammatory genes and decreased UCP1 expression in brown adipose tissue and
      activated p38 and ERK pathways in the liver of the KKay mice. CONCLUSIONS:
      Concentrated ambient PM2.5 exposure impairs energy metabolism, concomitant with
      abnormalities in glucose homeostasis, increased inflammation in insulin
      responsive organs, brown adipose inflammation and results in imbalance in
      circulating leptin/adiponectin levels in a genetically susceptible diabetic
      model. These results provide additional insights into the mechanisms surrounding
      air pollution mediated susceptibility to Type II DM.

PMID- 24886176
TI  - An inhibitor-driven study for enhancing the selectivity of indirubin derivatives
      towards leishmanial Glycogen Synthase Kinase-3 over leishmanial cdc2-related
      protein kinase 3.
AB  - BACKGROUND: In search of new antiparasitic agents for overcoming the limitations
      of current leishmaniasis chemotherapy, we have previously shown that 6
      bromoindirubin-3'-oxime (6BIO) and several other 6-substituted analogues of
      indirubin, a naturally occurring bis-indole present in mollusks and plants,
      displayed reverse selectivity from the respective mammalian kinases, targeting
      more potently the leishmanial Cyclin-Dependent Kinase-1 (CDK1) homologue [cdc2
      related protein kinase 3 (LCRK3)] over leishmanial Glycogen Synthase Kinase-3
      (LGSK-3). This reversal of selectivity in Leishmania parasites compared to
      mammalian cells makes the design of specific indirubin-based LGSK-3 inhibitors
      difficult. In this context, the identification of compounds bearing specific
      substitutions that shift indirubin inhibition towards LGSK-3, previously found to
      be a potential drug target, over LCRK3 is imperative for antileishmanial targeted
      drug discovery. METHODS: A new in-house indirubin library, composed of 35
      compounds, initially designed to target mammalian kinases (CDKs, GSK-3), was
      tested against Leishmania donovani promastigotes and intracellular amastigotes
      using the Alamar blue assay. Indirubins with antileishmanial activity were tested
      against LGSK-3 and LCRK3 kinases, purified from homologous expression systems.
      Flow cytometry (FACS) was used to measure the DNA content for cell-cycle analysis
      and the mode of cell death. Comparative structural analysis of the involved
      kinases was then performed using the Szmap algorithm. RESULTS: We have identified
      7 new indirubin analogues that are selective inhibitors of LGSK-3 over LCRK3.
      These new inhibitors were also found to display potent antileishmanial activity
      with GI50 values of <1.5 MUMU. Surprisingly, all the compounds that displayed
      enhanced selectivity towards LGSK-3, were 6BIO analogues bearing an additional 3'
      bulky amino substitution, namely a piperazine or pyrrolidine ring. A comparative
      structural analysis of the two aforementioned leishmanial kinases was
      subsequently undertaken to explain and rationalize the selectivity trend
      determined by the in vitro binding assays. Interestingly, the latter analysis
      showed that selectivity could be correlated with differences in kinase solvation
      thermo dynamics induced by minor sequence variations of the otherwise highly
      similar ATP binding pockets. CONCLUSIONS: In conclusion, 3'-bulky amino
      substituted 6-BIO derivatives, which demonstrate enhanced specificity towards
      LGSK-3, represent a new scaffold for targeted drug development to treat
      leishmaniasis.

PMID- 24886177
TI  - Overexpression of UCP1 in tobacco induces mitochondrial biogenesis and amplifies
      a broad stress response.
AB  - BACKGROUND: Uncoupling protein one (UCP1) is a mitochondrial inner membrane
      protein capable of uncoupling the electrochemical gradient from adenosine-5'
      triphosphate (ATP) synthesis, dissipating energy as heat. UCP1 plays a central
      role in nonshivering thermogenesis in the brown adipose tissue (BAT) of
      hibernating animals and small rodents. A UCP1 ortholog also occurs in plants, and
      aside from its role in uncoupling respiration from ATP synthesis, thereby wasting
      energy, it plays a beneficial role in the plant response to several abiotic
      stresses, possibly by decreasing the production of reactive oxygen species (ROS)
      and regulating cellular redox homeostasis. However, the molecular mechanisms by
      which UCP1 is associated with stress tolerance remain unknown. RESULTS: Here, we
      report that the overexpression of UCP1 increases mitochondrial biogenesis,
      increases the uncoupled respiration of isolated mitochondria, and decreases
      cellular ATP concentration. We observed that the overexpression of UCP1 alters
      mitochondrial bioenergetics and modulates mitochondrial-nuclear communication,
      inducing the upregulation of hundreds of nuclear- and mitochondrial-encoded
      mitochondrial proteins. Electron microscopy analysis showed that these metabolic
      changes were associated with alterations in mitochondrial number, area and
      morphology. Surprisingly, UCP1 overexpression also induces the upregulation of
      hundreds of stress-responsive genes, including some involved in the antioxidant
      defense system, such as superoxide dismutase (SOD), glutathione peroxidase (GPX)
      and glutathione-S-transferase (GST). As a consequence of the increased UCP1
      activity and increased expression of oxidative stress-responsive genes, the UCP1
      overexpressing plants showed reduced ROS accumulation. These beneficial metabolic
      effects may be responsible for the better performance of UCP1-overexpressing
      lines in low pH, high salt, high osmolarity, low temperature, and oxidative
      stress conditions. CONCLUSIONS: Overexpression of UCP1 in the mitochondrial inner
      membrane induced increased uncoupling respiration, decreased ROS accumulation
      under abiotic stresses, and diminished cellular ATP content. These events may
      have triggered the expression of mitochondrial and stress-responsive genes in a
      coordinated manner. Because these metabolic alterations did not impair plant
      growth and development, UCP1 overexpression can potentially be used to create
      crops better adapted to abiotic stress conditions.

PMID- 24886178
TI  - Intratumoral delivery of recombinant vaccinia virus encoding for ErbB2/Neu
      inhibits the growth of salivary gland carcinoma cells.
AB  - BACKGROUND: The antitumor activity induced by intratumoral vaccination with
      poxvirus expressing a tumor antigen was shown to be superior to that induced by
      subcutaneous vaccination. Salivary gland carcinomas overexpress ErbB2.
      Trastuzumab, a monoclonal antibody to ErbB2, was proposed for salivary gland
      tumors treatment. We explored the effectiveness of intratumoral vaccination with
      the recombinant vaccinia virus ErbB2/Neu (rV-neuT) vaccine in hampering the
      growth of transplanted Neu-overexpressing BALB-neuT salivary gland cancer cells
      (SALTO) in BALB-neuT mice. METHODS: BALB-neuT male mice were subcutaneously
      injected with SALTO tumor cells and intratumorally vaccinated twice with
      different doses of either rV-neuT or V-wt (wild-type). Tumors were measured
      weekly. The presence of anti-ErbB2/Neu antibodies was assayed by ELISA,
      immunoprecipitation or indirect immunofluorescence. Biological activity of immune
      sera was investigated by analyzing antibody-dependent cellular cytotoxicity
      (ADCC), SALTO cells proliferation and apoptosis, ErbB2/Neu receptor down
      regulation and ERK1/2 phosphorylation. Anti-Neu T cell immunity was investigated
      by determining the release of IL-2 and IFN-gamma in T cells supernatant. Survival
      curves were determined using the Kaplan-Meier method and compared using the log
      rank test. Differences in tumor volumes, number of apoptotic cells, titer of the
      serum, percentage of ADCC were evaluated through a two-tailed Student's t-test.
      RESULTS: rV-neuT intratumoral vaccination was able to inhibit the growth of SALTO
      cancer cells in a dose-dependent manner. The anti-Neu serum titer paralleled in
      vivo antitumor activity of rV-neuT vaccinated mice. rV-neuT immune serum was able
      to mediate ADCC, inhibition of SALTO cells proliferation, down regulation of the
      ErbB2/Neu receptor, inhibition of ERK1/2 phosphorylation and induction of
      apoptosis, thus suggesting potential mechanisms of in vivo tumor growth
      interference. In addition, spleen T cells of rV-neuT vaccinated mice released IFN
      gamma and IL-2 upon in vitro stimulation with several Neu-specific peptides
      located in the extracellular domain of Neu sequence. CONCLUSIONS: rV-neuT
      intratumoral vaccination could be employed to induce an efficient antitumor
      response and reject transplanted salivary gland tumors. Our findings may have
      important implications for the design of cancer vaccine protocols for the
      treatment of salivary gland tumors and other accessible tumors using intratumoral
      injection of recombinant vaccinia virus.

PMID- 24886179
TI  - Internet-delivered treatment: its potential as a low-intensity community
      intervention for adults with symptoms of depression: protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Depression is a high prevalence disorder, displaying high rates of
      lifetime incidence, early age onset, high chronicity, and role impairment. In
      Ireland 12-month prevalence of depression has been reported to be 10.3%. A large
      percentage of affected individuals have no medical diagnosis nor seek treatment.
      Cognitive Behavior Therapy (CBT) has established itself as an option for the
      treatment of depression. Many Irish adults with depression find it difficult to
      access evidence-based CBT, this is due to several factors, like stigma and costs.
      However, systematic factors including the shortage of trained professionals and
      the relative underdevelopment of services also make access difficult.Stepped-care
      can increase access to evidence-based CBT. One option is tailored internet
      delivered treatment programs. Preliminary research from Ireland needs now to
      include large-scale studies on effectiveness. Thus the current study seeks to
      examine the potential of an internet-delivered low-intensity treatment for
      symptoms of depression in an Irish adult community sample. METHOD/DESIGN: The
      study is a randomized controlled trial of an online CBT (iCBT) program for the
      treatment of adults with depressive symptoms. The trial will include an active
      treatment group and a waiting-list control group. The active condition will
      consist of 8 weekly modules of iCBT, with post-session feedback support.
      Participants in the waiting list will receive access to the treatment at week 8.
      Participants will complete the Beck Depression Inventory (BDI-II) and eligibility
      criteria will also apply. Primary outcomes are depressive symptoms. Secondary
      outcomes include quality of life indicators, significant events and satisfaction
      with online treatment. Data will be collected at baseline and at post-treatment,
      week 8, and at follow-up week 20 (3-months) and week 32 (6-months). Analysis will
      be conducted on the intention-to-treat basis. DISCUSSION: The study seeks to
      evaluate the effectiveness of an online delivered treatment for depression in a
      community sample of Irish adults with symptoms of depression. The study will be a
      first contribution and depending on the sample recruited the results may be
      generalizable to people with similar difficulties in Ireland and may therefore
      give insight into the potential of low-intensity interventions for Irish people
      with depressive symptoms. TRIAL REGISTRATION NUMBER: Current Controlled Trials
      ISRCTN03704676. DOI: 10.1186/ISRCTN03704676.

PMID- 24886180
TI  - Current evidences on XPC polymorphisms and gastric cancer susceptibility: a meta
      analysis.
AB  - BACKGROUND: Reduced DNA repair capacities due to inherited polymorphisms may
      increase the susceptibility to cancers including gastric cancer. Previous studies
      investigating the association between Xeroderma Pigmentosum group C (XPC) gene
      polymorphisms and gastric cancer risk reported inconsistent results. We performed
      a meta-analysis to summarize the possible association. METHODS: All studies
      published up to January 2014 on the association between XPC polymorphisms and
      gastric cancer risk were identified by searching electronic databases PubMed,
      EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The
      association between XPC polymorphisms and gastric cancer risk was assessed by
      odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS:
      Six studies with 1,355 gastric cancer cases and 2,573 controls were finally
      included in the meta-analysis. With respect to Lys939Gln polymorphism, we did not
      observe a significant association when all studies were pooled into the meta
      analysis. When stratified by ethnicity, source of control, and study quality,
      statistical significant association was not detected in all subgroups. With
      respect to Ala499Val and PAT-/+polymorphisms, we also did not observe any
      significant association with gastric cancer risk in the pooled analysis.
      CONCLUSIONS: This meta-analysis based on current evidences suggested that the XPC
      polymorphisms (Lys939Gln, Val499Arg, and PAT-/+) did not contribute to gastric
      cancer risk. Considering the limited sample size and ethnicity included in the
      meta-analysis, further larger scaled and well-designed studies are needed to
      confirm our results. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1485880312555069.

PMID- 24886181
TI  - Associations between housing and management factors and reproductive performance
      in 327 Norwegian sheep flocks.
AB  - BACKGROUND: Housing sheep in insulated, warm buildings, which is common in
      Norway, involves high buildings costs, but has not been reported to improve
      health and performance. Few studies have dealt with the association between
      housing and management and reproductive performance.Data on housing and
      management during the indoor period from a questionnaire were merged with herd
      level data from the Norwegian Sheep Recording System, and the material included
      327 sheep flocks. Associations between housing and management factors and
      reproductive performance were analyzed by means of multivariate regression models
      and grouped logistic regression. RESULTS: There was no difference in reproductive
      performance between warm and cold housing. Number of live born lambs born per
      pregnant ewe was highest in flocks with 10 or less ewes per pen, and lowest in
      flocks with more than 40 ewes per pen. Rate of barren ewes was lowest, and number
      of lambs per ewe at the end of the indoor period was highest in flocks where the
      sheep were regrouped according to number of foetuses (lambs) identified by
      scanning. A higher total number of lambs born per pregnant ewe and lambs per ewe
      at the end of the indoor period were found where other available housing
      facilities or outdoor areas were used in addition to the main housing unit in the
      lambing season. The rate of stillbirths was lowest on farms where sheep was the
      only animal production. None of the factors evaluated had any significant
      association with mortality of live born lambs in the indoor period. Lowest number
      of lambs per ewe at the end of the indoor period was found on farms where other
      family members/hired labour were caretakers as compared with the farmer or
      spouse/cohabitant, and highest numbers were found where caretakers were older
      than 60 years of age. Reproductive performance was lower in the Spael Breed than
      the Norwegian White Sheep. CONCLUSION: Housing systems per se are of minor
      importance, whereas management practices in the indoor period should be expected
      to improve reproductive performance.

PMID- 24886183
TI  - PCR detection and analysis of potentially zoonotic Hepatitis E virus in French
      rats.
AB  - BACKGROUND: Hepatitis E virus has been detected in a wide range of animals. While
      Genotypes 1-2 of this virus infect only humans, 3-4 can spread from animals to
      humans and cause sporadic cases of human disease. Pig, and possibly also rats,
      may act as a reservoir for virus. From a public health perspective it is
      important to clarify the role of rats for infection of humans. Rats often live
      close to humans and are therefore of special interest to public health. Rats live
      of waste and inside the sewage system and may become infected. Reports of
      hepatitis E virus in rats have been published but not from France. The
      possibility that rats in an urban area in France were Hepatitis E virus infected,
      with which type and relationship to other strains was investigated. This study
      provides information important to public health and better understanding the
      occurrence of hepatitis E virus in the environment.Eighty one rats (Rattus
      Norvegicus) were captured, euthanized, sampled (liver and faeces) and analyzed by
      real-time RT-PCR's, one specific for Hepatitis E virus in rats and one specific
      for genotype 1-4 that that is known to infect humans. Positive samples were
      analyzed by a nested broad spectrum RT-PCR, sequenced and compared with sequences
      in Genbank. FINDINGS: Twelve liver and 11 faeces samples out of 81 liver and 81
      faeces samples from 81 captured rats were positive in the PCR specific for
      Hepatitis E virus in rats and none in the PCR specific for genotype 1-4.
      Comparison by nucleotide BLAST showed a maximum of 87% similarity to Hepatitis E
      virus previously detected in rats and significantly less to genotype 1-4.
      CONCLUSIONS: This is the first study demonstrating that rats in France carries
      hepatitis E virus and provide information regarding its relation to other virus
      strains previously detected in rats and other host animals world-wide. Genotype 1
      4 was not detected.

PMID- 24886182
TI  - Neuroinflammation and related neuropathologies in APPSL mice: further value of
      this in vivo model of Alzheimer's disease.
AB  - BACKGROUND: Beyond cognitive decline, Alzheimer's disease (AD) is characterized
      by numerous neuropathological changes in the brain. Although animal models
      generally do not fully reflect the broad spectrum of disease-specific
      alterations, the APPSL mouse model is well known to display early plaque
      formation and to exhibit spatial learning and memory deficits. However, important
      neuropathological features, such as neuroinflammation and lipid peroxidation, and
      their progression over age, have not yet been described in this AD mouse model.
      METHODS: Hippocampal and neocortical tissues of APPSL mice at different ages were
      evaluated. One hemisphere from each mouse was examined for micro- and
      astrogliosis as well as concomitant plaque load. The other hemisphere was
      evaluated for lipid peroxidation (quantified by a thiobarbituric acid reactive
      substances (TBARS) assay), changes in Abeta abundance (Abeta38, Abeta40 and
      Abeta42 analyses), as well as determination of aggregated Abeta content (Amorfix
      A4 assay). Finally, correlation analyses were performed to illustrate the time
      dependent correlation between neuroinflammation and Abeta load (soluble,
      insoluble, fibrils), or lipid peroxidation, respectively. RESULTS: As is
      consistent with previous findings, neuroinflammation starts early and shows
      strong progression over age in the APPSL mouse model. An analyses of concomitant
      Abeta load and plaque deposition revealed a similar progression, and high
      correlations between neuroinflammation markers and soluble or insoluble Abeta or
      fibrillar amyloid plaque loads were observed. Lipid peroxidation, as measured by
      TBARS levels, correlates well with neuroinflammation in the neocortex but not the
      hippocampus. The hippocampal lipid peroxidation correlated strongly with the
      increase of LOC positive fiber load, whereas neocortical TBARS levels were
      unrelated to amyloidosis. CONCLUSIONS: These data illustrate for the first time
      the progression of major AD related neuropathological features other than plaque
      load in the APPSL mouse model. Specifically, we demonstrate that microgliosis and
      astrocytosis are prominent aspects of this AD mouse model. The strong correlation
      of neuroinflammation with amyloid burden and lipid peroxidation underlines the
      importance of these pathological factors for the development of AD. The new
      finding of a different relation of lipid peroxidation in the hippocampus and
      neocortical regions show that the model might contribute to the understanding of
      complex pathological mechanisms and their interplay in AD.

PMID- 24886184
TI  - Influence of sildenafil on blood oxygen saturation of the obstructed bladder.
AB  - BACKGROUND: Blood oxygen saturation (BOS) is decreased in a low-compliant,
      overactive obstructed bladder. The objective of this study is to determine the
      effect of Sildenafil (SC) on bladder function and BOS) in an in vivo animal model
      of bladder outlet obstruction. METHODS: Thirty-two guinea pigs; sham operated (n
      = 8), sham operated + SC (n = 8), urethrally obstructed (n = 8) and urethrally
      obstructed + SC (n = 8) were studied during an 8 week period. BOS of the bladder
      wall was measured by differential path-length spectroscopy (DPS) before
      obstruction, at day 0, and at week 8. The bladder function was evaluated by
      urodynamic studies every week. RESULTS: Before surgery and after sham operation
      all study parameters were comparable. After sham operation, bladder function and
      BOS did not change. In the obstructed group the urodynamic parameters were
      deteriorated and BOS was decreased. In the group obstruction + SC, bladder
      compliance remained normal and overactivity occurred only sporadic. BOS remained
      unchanged compared to the sham group and was significantly higher compared to the
      obstruction group. CONCLUSIONS: In an obstructed bladder the loss of bladder
      function is accompanied by a significant decrease in BOS. Treatment of obstructed
      bladders with SC yields a situation of high saturation, high bladder compliance
      and almost no overactivity. Maintaining the microcirculation of the bladder wall
      might result in better bladder performance without significant loss of bladder
      function. Measurement of BOS and interventions focussing on tissue
      microcirculation may have a place in the evaluation / treatment of various
      bladder dysfunctions.

PMID- 24886185
TI  - Hepatoprotective effects of early pentoxifylline administration on hepatic injury
      induced by concanavalin A in rat.
AB  - Tumor necrosis factor alpha (TNF-alpha) plays an important role in the
      pathogensis of hepatitis C virus (HCV) infection induced liver injury. This study
      aimed to evaluate the effects of TNF-alpha inhibition with pentoxifylline (PTX)
      on concanavalin A (Con A)-induced hepatic injury in rats. The rats were
      distributed among 3 groups: (i) control group (1 mL saline.week(-1) by
      intravenous injection (i.v.)); (ii) Con A treatment group (20 mg Con A.(kg body
      mass)(-1).week(-1), i.v.), and (iii) rats treated with Con A and with PTX (200 mg
      PTX.(kg body mass)(-1).day(-1), per oral) group. Blood samples and livers were
      collected at the end of weeks 1, 2, 4, and 8 of Con A treatment. Portal pressure
      (PP) was measured at the end of week 8. The administration of PTX was found to
      confer significant protection against the injurious effects of Con A on the
      liver, by reducing serum levels of aspartate aminotransferase, alanine
      aminotransferase, hepatic TNF-alpha, and malondialdehyde. Histopathological
      examination revealed that treatment with PTX significantly suppressed early
      inflammation, reduced alpha smooth muscle actin, and the apoptosis of hepatocytes
      induced by Con A. Moreover, PTX significantly (P < 0.05) reduced PP, and
      quantitative analyses of the area of fibrosis induced by treatment with Con A
      showed a significant reduction at the end of week 8. We conclude that rats
      treated with PTX revealed a more or less normal hepatocyte architecture as well
      as marked improvement in fibrosis and PP. 

PMID- 24886186
TI  - Introduction to the special issue on circadian rhythms in behavioral
      neuroscience.
AB  - Circadian rhythms influence virtually every aspect of behavior. This special
      issue provides updates on the current state and future directions for the field
      of circadian rhythms in behavioral neuroscience. Recent data have linked
      circadian rhythms to behavioral and physiological phenomena and disease states in
      virtually every area of behavioral and biomedical science. Specifically, a
      growing interest in the cognitive, neuropsychiatric, and metabolic consequences
      of circadian rhythm disorders and dysfunction is emerging. This special issue is
      not intended to provide an exhaustive overview of the entire field of
      chronobiology or behavioral rhythms. Instead, we invited researchers from a
      variety of fields to critically review and integrate studies that address the
      roles of circadian rhythms in behavioral neuroscience. The papers included in
      this issue range from the molecular biology of clock genes to the behavior of
      free-living animals, and cover a wide variety of species ranging from insects, to
      rodents, to humans. As such, the reviews provide an overview of the burgeoning
      field of circadian rhythms within behavioral neuroscience.

PMID- 24886187
TI  - Survival value of suprachiasmatic nuclei (SCN) in four wild sciurid rodents.
AB  - Laboratory and field data relevant to the survival value of the suprachiasmatic
      nuclei (SCN) pacemaker are presented for 4 related North American squirrel
      species that evolved in habitats with markedly different environmental
      conditions. Laboratory studies used free-running activity rhythms under constant
      conditions as the signature of an endogenous pacemaker. Field studies documented
      the circadian ecology of the 4 species; survival of intact controls was compared,
      when possible, with an SCN-lesioned group of free-living animals or with wild
      caught animals in a laboratory facility that simulated natural conditions. All 4
      species were rhythmic in the laboratory as indicated by precise free-running
      wheel-turning rhythms under constant conditions, as well as by photo-entrainment
      of free-runs to a 24-hr light-dark schedule. Southern flying squirrels (Glaucomys
      volans) presumably minimized predation by sleeping in sheltering tree dens during
      daylight, with awakening by their SCN timer for nocturnal gliding. Eastern
      chipmunks (Tamias striatus) were strictly diurnal but avoided predation in
      elaborate dens as well as by facultative hibernation and winter food caches.
      Antelope squirrels (Ammospermophilus leucurus) were also diurnal with dens for
      minimizing predation at night. Golden-mantled ground squirrels (Spermophilus
      lateralis) were diurnal, fossorial species with protective dens; during the
      extended hibernation in winter, the SCN played a role in limiting the time spent
      in arousal episodes. Thus, in the evolution of the physiology and behavior of
      these species, the SCN has become involved in diverse functions ranging from
      regulation of activity to reduction of energy expenditure during arousal episodes
      of hibernating ground squirrels.

PMID- 24886188
TI  - Monoamines and sleep in Drosophila.
AB  - Sleep is an important physiological state, but its function and regulation remain
      elusive. Drosophila melanogaster is a useful model organism for studying sleep
      because it has a well-established diurnal activity pattern, including
      consolidated periods of quiescence that share many characteristics with human
      sleep. Sleep behavior is regulated by circadian and homeostatic processes and is
      modulated by environmental and physiological context cues. These cues are
      communicated to sleep circuits by neurohormones and neuromodulators. A major
      class of neuromodulators, monoamines, has been found to be essential in various
      aspects of sleep regulation. Dopamine promotes arousal and sleep-dependent memory
      formation as well as daily activity. Octopamine, the insect homolog of
      norepinephrine, promotes wake and may play a role in circadian clock-dependent
      sleep and arousal. Serotonin promotes sleep and modulates circadian entrainment
      to light. The different monoamines each signal through multiple receptors in
      various brain regions in response to different conditions. How these separate
      circuits integrate their inputs into a single program of behavior is an open
      field of study for which Drosophila will continue to be a useful model. Monoamine
      biosynthetic pathways and receptors are conserved between flies and humans, and,
      thus far, their roles in modulating sleep also appear to be conserved.

PMID- 24886189
TI  - Adaptive and pathological inhibition of neuroplasticity associated with circadian
      rhythms and sleep.
AB  - The circadian system organizes sleep and wake through imposing a daily cycle of
      sleep propensity on the organism. Sleep has been shown to play an important role
      in learning and memory. Apart from the daily cycle of sleep propensity, however,
      direct effects of the circadian system on learning and memory also have been well
      documented. Many mechanistic components of the memory consolidation process
      ranging from the molecular to the systems level have been identified and studied.
      The question that remains is how do these various processes and components work
      together to produce cycles of increased and decreased learning abilities, and why
      should there be times of day when neural plasticity appears to be restricted?
      Insights into this complex problem can be gained through investigations of the
      learning disabilities caused by circadian disruption in Siberian hamsters and by
      aneuploidy in Down's syndrome mice. A simple working hypothesis that has been
      explored in this work is that the observed learning disabilities are due to an
      altered excitation/inhibition balance in the CNS. Excessive inhibition is the
      suspected cause of deficits in memory consolidation. In this article we present
      the evidence that excessive inhibition in these cases of learning disability
      involves GABAergic neurotransmission, that treatment with GABA receptor
      inhibitors can reverse the learning disability, and that the efficacy of the
      treatment is time sensitive coincident with the major daily sleep phase, and that
      it depends on sleep. The evidence we present leads us to hypothesize that a
      function of the circadian system is to reduce neuroplasticity during the daily
      sleep phase when processes of memory consolidation are taking place.

PMID- 24886191
TI  - Patient freedom to choose a weight loss diet in the treatment of overweight and
      obesity: a randomized dietary intervention in type 2 diabetes and pre-diabetes.
AB  - BACKGROUND: Offering the overweight or obese patient the option of choosing from
      a selection of weight loss diets has not been investigated in type 2 diabetes.
      The aim of the study was to investigate if the option to choose from, and
      interchange between a selection of diets ("Choice"), as opposed to being
      prescribed one set diet ("No Choice"), improves drop out rates and leads to
      improved weight loss and cardio-metabolic outcomes. METHODS: The study was a 12
      month, randomized parallel intervention. A total of 144 volunteers with type 2
      diabetes or pre-diabetes and a BMI >27 were randomized to "No Choice" or
      "Choice". Those in the No Choice group were placed on a set weight loss diet
      (CSIRO) with no change permitted. Those in the Choice group could choose from,
      and interchange between, the CSIRO, South Beach or Mediterranean diets. RESULTS:
      There were no differences in attrition rates or weight loss between the "Choice"
      and "No Choice". In a secondary analysis of the intention-to-treat weight loss
      data with last measured weight carried forward gave a highly significant diet
      group by time by gender interaction (p = 0.002) with men doing better in the No
      Choice group overall (maximum difference "No Choice "-2.9 +/- 4.6 kg vs. "Choice"
      6.2 kg +/- 5.3 kg at 6 months) and women doing better in the Choice group overall
      (maximum difference Choice -3.1 +/- 3.7 kg vs. "No Choice" -2.0 kg +/- 2.6 kg at
      6 months). CONCLUSIONS: Men prefer direction in their weight loss advice and do
      less well with choice. A gender-specific approach is recommended when prescribing
      weight loss diets. TRIAL REGISTRATION: anzctr.org.au ACTRN12612000310864.

PMID- 24886190
TI  - Dual RNA-seq transcriptional analysis of wheat roots colonized by Azospirillum
      brasilense reveals up-regulation of nutrient acquisition and cell cycle genes.
AB  - BACKGROUND: The rapid growth of the world's population demands an increase in
      food production that no longer can be reached by increasing amounts of
      nitrogenous fertilizers. Plant growth promoting bacteria (PGPB) might be an
      alternative to increase nitrogenous use efficiency (NUE) in important crops such
      wheat. Azospirillum brasilense is one of the most promising PGPB and wheat roots
      colonized by A. brasilense is a good model to investigate the molecular basis of
      plant-PGPB interaction including improvement in plant-NUE promoted by PGPB.
      RESULTS: We performed a dual RNA-Seq transcriptional profiling of wheat roots
      colonized by A. brasilense strain FP2. cDNA libraries from biological replicates
      of colonized and non-inoculated wheat roots were sequenced and mapped to wheat
      and A. brasilense reference sequences. The unmapped reads were assembled de novo.
      Overall, we identified 23,215 wheat expressed ESTs and 702 A. brasilense
      expressed transcripts. Bacterial colonization caused changes in the expression of
      776 wheat ESTs belonging to various functional categories, ranging from transport
      activity to biological regulation as well as defense mechanism, production of
      phytohormones and phytochemicals. In addition, genes encoding proteins related to
      bacterial chemotaxi, biofilm formation and nitrogen fixation were highly
      expressed in the sub-set of A. brasilense expressed genes. CONCLUSIONS: PGPB
      colonization enhanced the expression of plant genes related to nutrient up-take,
      nitrogen assimilation, DNA replication and regulation of cell division, which is
      consistent with a higher proportion of colonized root cells in the S-phase. Our
      data support the use of PGPB as an alternative to improve nutrient acquisition in
      important crops such as wheat, enhancing plant productivity and sustainability.

PMID- 24886193
TI  - Genetically shaping morphology of the filamentous fungus Aspergillus glaucus for
      production of antitumor polyketide aspergiolide A.
AB  - BACKGROUND: For filamentous fungi, the basic growth unit of hyphae usually makes
      it sensitive to shear stress which is generated from mechanical force and dynamic
      fluid in bioreactor, and it severely decreases microbial productions. The
      conventional strategies against shear-sensitive conundrum in fungal fermentation
      usually focus on adapting agitation, impeller type and bioreactor configuration,
      which brings high cost and tough work in industry. This study aims to genetically
      shape shear resistant morphology of shear-sensitive filamentous fungus
      Aspergillus glaucus to make it adapt to bioreactor so as to establish an
      efficient fermentation process. RESULTS: Hyphal morphology shaping by modifying
      polarized growth genes of A. glaucus was applied to reduce its shear-sensitivity
      and enhance aspergiolide A production. Degenerate PCR and genome walking were
      used to obtain polarized growth genes AgkipA and AgteaR, followed by construction
      of gene-deficient mutants by homologous integration of double crossover. Deletion
      of both genes caused meandering hyphae, for which, DeltaAgkipA led to small but
      intense curves comparing with DeltaAgteaR by morphology analysis. The germination
      of a second germ tube from conidiospore of the mutants became random while colony
      growth and development almost maintained the same. Morphology of DeltaAgkipA and
      DeltaAgteaR mutants turned to be compact pellet and loose clump in liquid
      culture, respectively. The curved hyphae of both mutants showed no remarkably
      resistant to glass bead grinding comparing with the wild type strain. However,
      they generated greatly different broth rheology which further caused growth and
      metabolism variations in bioreactor fermentations. By forming pellets, the
      DeltaAgkipA mutant created a tank environment with low-viscosity, low shear
      stress and high dissolved oxygen tension, leading to high production of
      aspergiolide A (121.7 +/- 2.3 mg/L), which was 82.2% higher than the wild type.
      CONCLUSIONS: A new strategy for shaping fungal morphology by modifying polarized
      growth genes was applied in submerged fermentation in bioreactor. This work
      provides useful information of shaping fungal morphology for submerged
      fermentation by genetically modification, which could be valuable for morphology
      improvement of industrial filamentous fungi.

PMID- 24886194
TI  - Genomic profile of ovarian carcinomas.
AB  - BACKGROUND: It is known that all tumors studied in sufficient number to draw
      conclusions show characteristic/specific chromosomal rearrangements, and the
      identification of these chromosomes and the genes rearranged behind the
      aberrations may ultimately lead to a tailor-made therapy for each cancer patient.
      Knowledge about the acquired genomic aberrations of ovarian carcinomas is still
      unsatisfactory. METHODS: We cytogenetically analyzed 110 new cases of ovarian
      carcinoma of different histological subtypes using karyotyping of G-banded
      chromosomes and high-resolution comparative genomic hybridization. We first
      compared the aberration patterns identified by the two genomic screening
      techniques using the so-called "classical" pathological classification in which
      the carcinomas are grouped as tumors of types I and II. We also broke down our
      findings according to the more "modern" classification which groups the
      carcinomas in five different categories. RESULTS: The chromosomal breakpoints
      identified by karyotyping tended to cluster to 19p/q and to 11q, but no
      unquestionably recurrent rearrangement could be seen. Common imbalances were
      scored as gains from 1q, 3q, 7q, and 8q and losses from 17p, 19q, and 22q. Gain
      of material from 8q23 and losses from 19q and 22q have previously been described
      at high frequencies in bilateral and borderline ovarian carcinomas. The fact that
      they were present both in "precursor" lesions, i.e., borderline tumors, as well
      as in tumors of more advanced stages, i.e., carcinomas, highlights the
      possibility of an adenoma-carcinoma sequence in ovarian carcinogenesis.
      CONCLUSION: Based on the relatively simple genomic changes we identified in the
      low-grade serous carcinomas examined (n = 7) and which largely corresponded to
      the aberration pattern formerly identified in borderline tumors, one can
      interpret the cytogenetic data as supporting the view that the low-grade
      carcinomas represent a phenotypically more advanced stage of borderline tumors.
      Whether transition from low-grade to high-grade carcinoma also occurs, is a
      question about which the genomic data is still inconclusive.

PMID- 24886192
TI  - Dietary ascorbic acid and subsequent change in body weight and waist
      circumference: associations may depend on genetic predisposition to obesity--a
      prospective study of three independent cohorts.
AB  - BACKGROUND: Cross-sectional data suggests that a low level of plasma ascorbic
      acid positively associates with both Body Mass Index (BMI) and Waist
      Circumference (WC). This leads to questions about a possible relationship between
      dietary intake of ascorbic acid and subsequent changes in anthropometry, and
      whether such associations may depend on genetic predisposition to obesity. Hence,
      we examined whether dietary ascorbic acid, possibly in interaction with the
      genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI
      (WHR), associates with subsequent annual changes in weight (?BW) and waist
      circumference (?WC). METHODS: A total of 7,569 participants' from MONICA, the
      Diet Cancer and Health study and the INTER99 study were included in the study. We
      combined 50 obesity associated single nucleotide polymorphisms (SNPs) in four
      genetic scores: a score of all SNPs and a score for each of the traits (BMI, WC
      and WHR) with which the SNPs associate. Linear regression was used to examine the
      association between ascorbic acid intake and DeltaBW or DeltaWC. SNP-score *
      ascorbic acid interactions were examined by adding product terms to the models.
      RESULTS: We found no significant associations between dietary ascorbic acid and
      ?BW or ?WC. Regarding SNP-score * ascorbic acid interactions, each additional
      risk allele of the 14 WHR associated SNPs associated with a ?WC of 0.039 cm/year
      (P = 0.02, 95% CI: 0.005 to 0.073) per 100 mg/day higher ascorbic acid intake.
      However, the association to ?WC only remained borderline significant after
      adjustment for ?BW. CONCLUSION: In general, our study does not support an
      association between dietary ascorbic acid and ?BW or ?WC, but a diet with a high
      content of ascorbic acid may be weakly associated to higher WC gain among people
      who are genetically predisposed to a high WHR. However, given the quite limited
      association any public health relevance is questionable.

PMID- 24886195
TI  - Isolation and functional characterization of JcFT, a FLOWERING LOCUS T (FT)
      homologous gene from the biofuel plant Jatropha curcas.
AB  - BACKGROUND: Physic nut (Jatropha curcas L.) is a potential feedstock for biofuel
      production because Jatropha oil is highly suitable for the production of the
      biodiesel and bio-jet fuels. However, Jatropha exhibits low seed yield as a
      result of unreliable and poor flowering. FLOWERING LOCUS T (FT) -like genes are
      important flowering regulators in higher plants. To date, the flowering genes in
      Jatropha have not yet been identified or characterized. RESULTS: To better
      understand the genetic control of flowering in Jatropha, an FT homolog was
      isolated from Jatropha and designated as JcFT. Sequence analysis and phylogenetic
      relationship of JcFT revealed a high sequence similarity with the FT genes of
      Litchi chinensis, Populus nigra and other perennial plants. JcFT was expressed in
      all tissues of adult plants except young leaves, with the highest expression
      level in female flowers. Overexpression of JcFT in Arabidopsis and Jatropha using
      the constitutive promoter cauliflower mosaic virus 35S or the phloem-specific
      promoter Arabidopsis SUCROSE TRANSPORTER 2 promoter resulted in an extremely
      early flowering phenotype. Furthermore, several flowering genes downstream of
      JcFT were up-regulated in the JcFT-overexpression transgenic plant lines.
      CONCLUSIONS: JcFT may encode a florigen that acts as a key regulator in flowering
      pathway. This study is the first to functionally characterize a flowering gene,
      namely, JcFT, in the biofuel plant Jatropha.

PMID- 24886197
TI  - Vincristine-induced vocal cord palsy and successful re-treatment in a patient
      with diffuse large B cell lymphoma: a case report.
AB  - BACKGROUND: Vincristine, a type of vinca alkaloid, is widely used in the
      treatment of various childhood and adult malignancies. A well-known side effect
      of vincristine is its neurotoxicity and it is rarely indicted in vagus nerve
      involvement. Vincristine induced vocal cord palsy is a potentially reversible
      condition, with the mainstay of therapy being withdrawal of the offending drug.
      However, there are no clear guidelines regarding the possibility of re-treatment
      with the causative agent. CASE PRESENTATION: A 58 year old Asian male presented
      with constipation and abdominal distension. Diagnostic investigations revealed
      stage IVB diffuse large B cell lymphoma (DLBCL). The patient was subsequently
      started on R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and
      Prednisolone). On day twelve of receiving course four of R-CHOP, our patient
      presented to the hospital with a history of hoarseness of voice. Clinical and
      radiological examination revealed bilateral vocal cord palsy. Tracheostomy was
      done in view of a compromised airway. The patient subsequently went on to receive
      two more cycles of R-CHOP. Two weeks later Flexible laryngoscopy showed no lesion
      and the vocal cords were moving normally. The tracheostomy was removed. His voice
      has improved since and the patient is currently in remission. CONCLUSION: The
      occurrence of vincristine induced vocal cord palsy has been well reported in the
      literature. We strongly believe that our patient developed vocal cord palsy
      secondary to vincristine. The uniqueness of our patient's case lies in successful
      re-treatment of our patient with the offending drug. To the best of our knowledge
      this is the third instance where a patient was successfully re-treated with
      vincristine after having developed vocal cord palsy as a result of its use.

PMID- 24886196
TI  - Oral lymphomatoid granulomatosis, the first sign of a 'rare disease': a case
      report.
AB  - INTRODUCTION: Lymphomatoid granulomatosis is an uncommon Epstein-Barr virus
      positive B-cell lymphoma, an angiocentric-destructive process with a predominant
      T-cell background. Lymphomatoid granulomatosis is listed among rare diseases.
      Common localization is in the lungs. Lymphomatoid granulomatosis with oral
      involvement is described in only two reports. In this report, we describe a third
      case of oral lymphomatoid granulomatosis. CASE PRESENTATION: A 65-year-old
      Caucasian man with a gingival ulceration underwent a biopsy. The histological
      pattern was compatible with a grade III lymphomatoid granulomatosis. The staging
      revealed a nodular lesion in the lower lobe of his right lung. Our patient also
      presented with hemoptysis, an unusual and not reported clinical sign. Rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy was
      performed every three weeks for six cycles. CONCLUSIONS: The pulmonary nodule and
      the gingival lesion disappeared. At eight-month follow-up, our patient is disease
      free. We wish to emphasize that the oral manifestation described was the first
      sign of the disease and allowed for diagnosis. This case report adds to the
      medical literature for the particular clinical presentation of this rare disease.

PMID- 24886198
TI  - Increased frontal brain activation during walking while dual tasking: an fNIRS
      study in healthy young adults.
AB  - BACKGROUND: Accumulating evidence suggests that gait is influenced by higher
      order cognitive and cortical control mechanisms. Recently, several studies used
      functional near infrared spectroscopy (fNIRS) to examine brain activity during
      walking, demonstrating increased oxygenated hemoglobin (HbO2) levels in the
      frontal cortex during walking while subjects completed a verbal cognitive task.
      It is, however, still unclear whether this increase in activation was related to
      verbalization, if the response was specific to gait, or if it would also be
      observed during standing, a different motor control task. The aim of this study
      was to investigate whether an increase in frontal activation is specific to dual
      tasking during walking. METHODS: Twenty-three healthy young adults (mean 30.9 +/-
      3.7 yrs, 13 females) were assessed using an electronic walkway. Frontal brain
      activation was assessed using an fNIRS system consisting of two probes placed on
      the forehead of the subjects. Assessments included: walking in a self-selected
      speed; walking while counting forward; walking while serially subtracting 7s
      (Walking+S7); and standing while serially subtracting 7s (Standing+S7). Data was
      collected from 5 walks of 30 meters in each condition. Twenty seconds of quiet
      standing before each walk served as baseline frontal lobe activity. Repeated
      Measures Analysis of Variance (RM ANOVA) tested for differences between the
      conditions. RESULTS: Significant differences were observed in HbO2 levels between
      all conditions (p = 0.007). HbO2 levels appeared to be graded; walking alone
      demonstrated the lowest levels of HbO2 followed by walking+counting condition (p
      = 0.03) followed by Walking+S7 condition significantly increased compared to the
      two other walking conditions (p < 0.01). No significant differences in HbO2
      levels were observed between usual walking and the standing condition (p = 0.38)
      or between standing with or without serial subtraction (p = 0.76). CONCLUSIONS:
      This study provides direct evidence that dual tasking during walking is
      associated with frontal brain activation in healthy young adults. The observed
      changes are apparently not a response to the verbalization of words and are
      related to the cognitive load during gait.

PMID- 24886200
TI  - Changes in family income status and the development of overweight and obesity
      from 2 to 15 years: a longitudinal study.
AB  - BACKGROUND: An emerging body of research suggests the trajectory of a family's
      income affects children's health and development more profoundly than the often
      measured income at a single time point. The purpose of this study was to examine
      the associations between changes in family income status, early-life risk
      factors, and body mass index (BMI) z-score trajectory from age 2 to 15 years.
      METHODS: This longitudinal study employed a birth cohort (n = 595) located in a
      rural region of New York State. Data were collected through an audit of medical
      records and mailed questionnaires. Family low-income and BMI z-score trajectories
      were identified using latent-class modeling techniques that group children based
      on similar trends across time. We examined five early-life risk factors in
      relation to income and BMI z-score trajectories: maternal overweight/obesity,
      maternal gestational weight gain, maternal smoking during pregnancy,
      breastfeeding duration, and early-life weight gain trajectory. We used
      multinomial logistic regression models to estimate the odds of being in a BMI z
      score trajectory group based on income trajectory and early-life risk factors.
      RESULTS: Children who remain low-income throughout childhood were more likely to
      maintain overweight (AOR = 2.55, 95% CI = 1.03, 5.42) and children who moved into
      low-income during childhood were more likely to be obese (AOR = 2.36, 95% CI =
      1.12, 5.93) compared to children who were never low-income. Maternal
      overweight/obesity was significantly associated with a child become obese (AOR =
      8.31, 95% CI = 3.80, 18.20), become overweight (AOR = 2.37, 95% CI = 1.34, 4.22),
      and stay overweight (AOR = 1.79, 95% CI = 1.02, 3.14). Excessive gestational
      weight gain was associated with increased likelihood of a child becoming
      overweight trajectory (AOR = 2.01, 95% CI = 1.01, 4.00). CONCLUSIONS: Our
      findings further supports the growing evidence that there are several preventable
      early-life risk factors that could be targeted for intervention. This study
      provides new evidence that remaining in low-income and moving into low-income
      increases risk for adolescent overweight and obesity.

PMID- 24886202
TI  - An R package that automatically collects and archives details for reproducible
      computing.
AB  - BACKGROUND: It is scientifically and ethically imperative that the results of
      statistical analysis of biomedical research data be computationally reproducible
      in the sense that the reported results can be easily recapitulated from the study
      data. Some statistical analyses are computationally a function of many data
      files, program files, and other details that are updated or corrected over time.
      In many applications, it is infeasible to manually maintain an accurate and
      complete record of all these details about a particular analysis. RESULTS:
      Therefore, we developed the rctrack package that automatically collects and
      archives read only copies of program files, data files, and other details needed
      to computationally reproduce an analysis. CONCLUSIONS: The rctrack package uses
      the trace function to temporarily embed detail collection procedures into
      functions that read files, write files, or generate random numbers so that no
      special modifications of the primary R program are necessary. At the conclusion
      of the analysis, rctrack uses these details to automatically generate a read only
      archive of data files, program files, result files, and other details needed to
      recapitulate the analysis results. Information about this archive may be included
      as an appendix of a report generated by Sweave or knitR. Here, we describe the
      usage, implementation, and other features of the rctrack package. The rctrack
      package is freely available from
      http://www.stjuderesearch.org/site/depts/biostats/rctrack under the GPL license.

PMID- 24886201
TI  - Reporting of context and implementation in studies of global health
      interventions: a pilot study.
AB  - BACKGROUND: There is an increasing push for 'evidence-based' decision making in
      global health policy circles. However, at present there are no agreed upon
      standards or guidelines for how to evaluate evidence in global health. Recent
      evaluations of existing evidence frameworks that could serve such a purpose have
      identified details of program context and project implementation as missing
      components needed to inform policy. We performed a pilot study to assess the
      current state of reporting of context and implementation in studies of global
      health interventions. METHODS: We identified three existing criteria sets for
      implementation reporting and selected from them 10 criteria potentially relevant
      to the needs of policy makers in global health contexts. We applied these 10
      criteria to 15 articles included in the evidence base for three global health
      interventions chosen to represent a diverse set of advocated global health
      programs or interventions: household water chlorination, prevention of mother-to
      child transmission of HIV, and lay community health workers to reduce child
      mortality. We used a good-fair-poor/none scale for the ratings. RESULTS: The
      proportion of criteria for which reporting was poor/none ranged from 11% to 54%
      with an average of 30%. Eight articles had 'good' or 'fair' documentation for
      greater than 75% of criteria, while five articles had 'poor or none'
      documentation for 50% of criteria or more. Examples of good reporting were
      identified. CONCLUSIONS: Reporting of context and implementation information in
      studies of global health interventions is mostly fair or poor, and highly
      variable. The idiosyncratic variability in reporting indicates that global health
      investigators need more guidance about what aspects of context and implementation
      to measure and how to report them. This lack of context and implementation
      information is a major gap in the evidence needed by global health policy makers
      to reach decisions.

PMID- 24886203
TI  - Homozygous deletion of the activin A receptor, type IB gene is associated with an
      aggressive cancer phenotype in pancreatic cancer.
AB  - BACKGROUND: Transforming growth factor, beta (TGFB) signal is considered to be a
      tumor suppressive pathway based on the frequent genomic deletion of the SMAD4
      gene in pancreatic cancer (PC); however; the role of the activin signal, which
      also belongs to the TGFB superfamily, remains largely unclear. METHODS AND
      RESULTS: We found a homozygous deletion of the activin A receptor, type IB
      (ACVR1B) gene in 2 out of 8 PC cell lines using array-comparative genomic
      hybridization, and the absence of ACVR1B mRNA and protein expression was
      confirmed in these 2 cell lines. Activin A stimulation inhibited cellular growth
      and increased the phosphorylation level of SMAD2 and the expression level of
      p21CIP1/WAF1 in the Sui66 cell line (wild-type ACVR1B and SMAD4 genes) but not in
      the Sui68 cell line (homozygous deletion of ACVR1B gene). Stable ACVR1B-knockdown
      using short hairpin RNA cancelled the effects of activin A on the cellular growth
      of the PC cell lines. In addition, ACVR1B-knockdown significantly enhanced the
      cellular growth and colony formation abilities, compared with controls. In a
      xenograft study, ACVR1B-knockdown resulted in a significantly elevated level of
      tumorigenesis and a larger tumor volume, compared with the control. Furthermore,
      in clinical samples, 6 of the 29 PC samples (20.7%) carried a deletion of the
      ACVR1B gene, while 10 of the 29 samples (34.5%) carried a deletion of the SMAD4
      gene. Of note, 5 of the 6 samples with a deletion of the ACVR1B gene also had a
      deletion of the SMAD4 gene. CONCLUSION: We identified a homozygous deletion of
      the ACVR1B gene in PC cell lines and clinical samples and proposed that the
      deletion of the ACVR1B gene may mediate an aggressive cancer phenotype in PC. Our
      findings provide novel insight into the role of the activin signal in PC.

PMID- 24886204
TI  - Tumor loci and their interactions on mouse chromosome 19 that contribute to
      testicular germ cell tumors.
AB  - BACKGROUND: Complex genetic factors underlie testicular germ cell tumor (TGCT)
      development. One experimental approach to dissect the genetics of TGCT
      predisposition is to use chromosome substitution strains, such as the 129.MOLF
      Chr 19 (M19). M19 carries chromosome (Chr) 19 from the MOLF whereas all other
      chromosomes are from the 129 strain. 71% of M19 males develop TGCTs in contrast
      to 5% in 129 strain. To identify and map tumor loci from M19 we generated
      congenic strains harboring MOLF chromosome 19 segments on 129 strain background
      and monitored their TGCT incidence. RESULTS: We found 3 congenic strains that
      each harbored tumor promoting loci that had high (14%-32%) whereas 2 other
      congenics had low (4%) TGCT incidences. To determine how multiple loci influence
      TGCT development, we created double and triple congenic strains. We found
      additive interactions were predominant when 2 loci were combined in double
      congenic strains. Surprisingly, we found an example where 2 loci, both which do
      not contribute significantly to TGCT, when combined in a double congenic strain
      resulted in greater than expected TGCT incidence (positive interaction). In an
      opposite example, when 2 loci with high TGCT incidences were combined, males of
      the double congenic showed lower than expected TGCT incidence (negative
      interaction). For the triple congenic strain, depending on the analysis, the
      overall TGCT incidence could be additive or could also be due to a positive
      interaction of one region with others. Additionally, we identified loci that
      promote bilateral tumors or testicular abnormalities. CONCLUSIONS: The congenic
      strains each with their characteristic TGCT incidences, laterality of tumors and
      incidence of testicular abnormalities, are useful for identification of TGCT
      susceptibility modifier genes that map to Chr 19 and also for studies on the
      genetic and environmental causes of TGCT development. TGCTs are a consequence of
      aberrant germ cell and testis development. By defining predisposing loci and some
      of the locus interactions from M19, this study further advances our understanding
      of the complex genetics of TGCTs, which is the most common cancer in young human
      males.

PMID- 24886205
TI  - Road traffic noise frequency and prevalent hypertension in Taichung, Taiwan: a
      cross-sectional study.
AB  - BACKGROUND: Epidemiological studies have reported the association between
      hypertension and exposure to road traffic noise, but the association between
      noise frequency characteristics is not clear. This study investigated the
      association between exposure to different frequency components of road traffic
      noise and the prevalence of hypertension in central Taiwan. METHODS: We recruited
      820 residents living near main roads for more than 3 years. Frequency components
      of traffic noise and traffic flow rates during 0900-1700 on weekdays were
      measured simultaneously in 2008. Multiple logistic regressions were conducted to
      estimate odds ratios (ORs) for diagnosed hypertension, adjusting for potential
      confounders and the total traffic flow rate. RESULTS: The high-exposure group (>=
      the median of noise levels [decibels, dB]) at 63 Hz, 125 Hz and 1000 Hz had ORs
      for hypertension of 2.77 (95% confidence interval [CI]: 1.17-6.52), 4.08 (95% CI:
      1.57-10.63) and 1.98 (1.00-3.92) (95% CI: 1.00-3.92), respectively, compared to
      the low-exposure group (< the median of noise levels [dB]). There was an
      increasing trend in the prevalence of hypertension by exposure to road traffic
      noise at 63, 125 and 1000 Hz in all subjects and in men. Total subjects exposed
      to >= 51 dB at 125 Hz had an OR of 4.65 (95% CI = 1.46-14.83) compared to those
      exposed to < 47 dB. CONCLUSIONS: With the possible bias of exposure
      misclassification and a bias from using diagnosed hypertension, these results
      suggest that exposure to road traffic noise at low and hearing-sensitive
      frequencies may be associated with hypertension and exposure to noise at 125 Hz
      may have the greatest risk for hypertension.

PMID- 24886206
TI  - Design of a school-based randomized trial to reduce smoking among 13 to 15-year
      olds, the X:IT study.
AB  - BACKGROUND: Adolescent smoking is still highly prevalent in Denmark. One in four
      13-year olds indicates that they have tried to smoke, and one in four 15-year
      olds answer that they smoke regularly. Smoking is more prevalent in
      socioeconomically disadvantaged populations in Denmark as well as in most Western
      countries. Previous school-based programs to prevent smoking have shown
      contrasting results internationally. In Denmark, previous programs have shown
      limited or no effect. This indicates a need for developing a well-designed,
      comprehensive, and multi-component intervention aimed at Danish schools with
      careful implementation and thorough evaluation.This paper describes X:IT, a study
      including 1) the development of a 3-year school-based multi-component
      intervention and 2) the randomized trial investigating the effect of the
      intervention. The study aims at reducing the prevalence of smoking among 13 to 15
      year olds by 25%. METHODS/DESIGN: The X:IT study is based on the Theory of
      Triadic Influences. The theory organizes factors influencing adolescent smoking
      into three streams: cultural environment, social situation, and personal factors.
      We added a fourth stream, the community aspects. The X:IT program comprises three
      main components: 1) smoke-free school premises, 2) parental involvement including
      smoke-free dialogues and smoke-free contracts between students and parents, and
      3) a curricular component. The study encompasses process- and effect-evaluations
      as well as health economic analyses. Ninety-four schools in 17 municipalities
      were randomly allocated to the intervention (51 schools) or control (43 schools)
      group. At baseline in September 2010, 4,468 year 7 students were eligible of
      which 4,167 answered the baseline questionnaire (response rate = 93.3%).
      DISCUSSION: The X:IT study is a large, randomized controlled trial evaluating the
      effect of an intervention, based on components proven to be efficient in other
      Nordic settings. The X:IT study directs students, their parents, and smoking
      prevention policies at the schools. These elements have proven to be effective
      tools in preventing smoking among adolescents. Program implementation is
      thoroughly evaluated to be able to add to the current knowledge of the importance
      of implementation. X:IT creates the basis for thorough effect and process
      evaluation, focusing on various social groups. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN77415416.

PMID- 24886208
TI  - Microvascular obstruction assessed by 3-tesla magnetic resonance imaging in acute
      myocardial infarction is correlated with plasma troponin I levels.
AB  - BACKGROUND: Microvascular obstruction (MVO) at the acute phase of myocardial
      infarction (MI) is associated with poor prognosis. We aimed to evaluate the
      correlation between plasma cardiac troponin I (cTnI) at the acute phase of MI and
      extent of no-reflow, as assessed by 3-T cardiac magnetic resonance imaging (MRI).
      Secondly, we defined a cut-off value for cTnI predictive of no-reflow. METHODS:
      51 consecutive patients with no previous history of cardiovascular disease,
      presenting ST elevation MI within <12 h. Infarct size and extent of no-reflow
      were evaluated by 3-T MRI at day 5. Extent of no-reflow at 15 minutes (MVO) was
      correlated with cTnI at admission, 6, 12, 24, 48 and 72 hours. At 6 months, MRI
      was performed to evaluate the impact of MVO on LV remodeling. RESULTS: MVO was
      diagnosed in 29 patients (57%). Extent of MVO was significantly correlated to
      peak troponin, cTnI (except admission values) and area under the curve. Using
      Receiver-operating characteristic (ROC) curve analysis, a cut-off cTnI value >89
      ng/mL at 12 h seemed to best predict presence of early MVO (sensitivity 63%,
      specificity 88%). At 6 months, MVO was associated with left ventricular (LV)
      remodeling, resulting in higher LV volumes. CONCLUSION: There is a relationship
      between cTnI at the acute phase of AMI and extent of MVO as assessed by 3-T
      cardiac MRI. A cut-off cTnI value of 89 ng/mL at 12 h seems to best predict
      presence of MVO, which contributes to LV remodeling.

PMID- 24886207
TI  - A novel treatment strategy of new onset atrial fibrillation after cardiac
      surgery: an observational prospective study.
AB  - OBJECTIVE: The aim of this prospective observational study was to evaluate the
      efficiency of a new escalating treatment strategy with vernakalant, flecainide
      and electrical cardioversion (EC) in patients with new onset atrial fibrillation
      (AF) after cardiac surgery. MATERIAL AND METHODS: 24 patients with new onset AF
      after aortic valve surgery, coronary artery bypass surgery or combined procedures
      were evaluated in this study. Additional including criteria were age between 18
      and 80, duration of AF less than four days, body weight less than 100 kg and no
      previous treatment with class I or III antiarrhythmic drugs. Exclusion criteria
      were poor left ventricular ejection fraction (LVEF < 40%) and history of
      myocardial infarction within 30 days. The patients were divided into converters
      and non-converters according to their response to combination treatment with
      vernakalant and flecainide, and the groups were compared. RESULTS: The mean age
      of the population was 69.6 +/- 6.3 years and 26.1% of patients were female. There
      were no statistically significant differences between the two groups in terms of
      height, weight, gender distribution, comorbidities, preoperative medication, left
      ventricular function and left atrium diameter. Interventricular septum (IVS) in
      the non-converted group was significantly thicker compared to the converted
      group: 14.0 +/- 1.00 vs. 10.40 +/- 2.59 mm (p = 0.036). While 14 patients (60.9%)
      were successfully converted into stable sinus rhythm by pharmacological treatment
      with vernakalant and flecainide, 9 patients (39.1%, non-converted group) remained
      in AF. However, seven of them could be converted after additional EC. CONCLUSION:
      The combination of vernakalant and flecainide improves the conversion rate into a
      stable sinus rhythm in postcardiotomy patients with new onset AF compared to
      single drug therapy. Furthermore it might be an excellent precondition for
      successful EC in patients who are not converted after using both antiarrhtythmic
      drugs. Furthermore, left ventricular hypertrophy might be a potential negative
      predictor of successful pharmacological cardioversion.

PMID- 24886209
TI  - Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral
      cancer patients at low risk of neck metastasis.
AB  - BACKGROUND: Metastasis to the cervical (neck) lymph nodes is one of the most
      significant clinical factors responsible for death from oral squamous cell
      carcinoma (SCC). Therefore, the lymph nodes are frequently removed when the tumor
      is excised (neck dissection), even though the majority of patients will not
      benefit from the extra surgery. Two subtypes of oral SCC distinguished by the
      presence of tumor genomic aberrations +3q, -8p, +8q and/or +20 differ in risk for
      metastasis - high for the 3q8pq20 subtype, harboring one or more of the
      aberrations and low for the non-3q8pq20 subtype, lacking these alterations. A
      prior analysis of the literature suggested genes differentially methylated in the
      two subtypes. Therefore, the goal of this study was to further investigate the
      methylation status of candidate biomarkers of the non-3q8pq20 subtype, and
      evaluate their utility for identifying patients at low risk for metastasis.
      METHODS: Methylation status of genes in a cohort of 52 oral SCC patients with at
      least five year follow up was determined by pyrosequencing. Gene expression
      levels were determined by quantitative RT-PCR. Growth following re-expression of
      HOXA9 in cultured oral SCC cells was assessed by proliferation and colony
      formation assays. RESULTS: A pilot study evaluating methylation levels of HOXA9,
      MT1A and HOXA11 promoters in DNA from 12 tumors (six each of the 3q8pq20 and non
      3q8pq20 subtypes) revealed that only HOXA9 was differentially methylated.
      Significant differences in methylation levels of HOXA9 were observed amongst the
      52 oral SCCs with respect to genomic subtype and nodal status (p = 0.014, and p =
      0.024, respectively, Wilcoxon rank sum test). High levels of HOXA9 methylation
      and low levels of expression in oral SCC cell lines were observed compared to
      HaCaT, a non-tumorigenic keratinocyte cell line. Re-expression of HOXA9 in the
      SCC4 oral cancer cell line resulted in diminished proliferation and colony
      formation. CONCLUSIONS: HOXA9 methylation is frequent in oral cancers and levels
      are higher in tumors with greater risk of metastasis. Expression of HOXA9 is low
      in cells with high levels of methylation and reduced expression appears to confer
      a growth advantage.

PMID- 24886210
TI  - Network topology-based detection of differential gene regulation and regulatory
      switches in cell metabolism and signaling.
AB  - BACKGROUND: Common approaches to pathway analysis treat pathways merely as lists
      of genes disregarding their topological structures, that is, ignoring the genes'
      interactions on which a pathway's cellular function depends. In contrast,
      PathWave has been developed for the analysis of high-throughput gene expression
      data that explicitly takes the topology of networks into account to identify both
      global dysregulation of and localized (switch-like) regulatory shifts within
      metabolic and signaling pathways. For this purpose, it applies adjusted wavelet
      transforms on optimized 2D grid representations of curated pathway maps. RESULTS:
      Here, we present the new version of PathWave with several substantial
      improvements including a new method for optimally mapping pathway networks unto
      compact 2D lattice grids, a more flexible and user-friendly interface, and pre
      arranged 2D grid representations. These pathway representations are assembled for
      several species now comprising H. sapiens, M. musculus, D. melanogaster, D.
      rerio, C. elegans, and E. coli. We show that PathWave is more sensitive than
      common approaches and apply it to RNA-seq expression data, identifying crucial
      metabolic pathways in lung adenocarcinoma, as well as microarray expression data,
      identifying pathways involved in longevity of Drosophila. CONCLUSIONS: PathWave
      is a generic method for pathway analysis complementing established tools like
      GSEA, and the update comprises efficient new features. In contrast to the tested
      commonly applied approaches which do not take network topology into account,
      PathWave enables identifying pathways that are either known be involved in or
      very likely associated with such diverse conditions as human lung cancer or aging
      of D. melanogaster. The PathWave R package is freely available at
      http://www.ichip.de/software/pathwave.html.

PMID- 24886211
TI  - A cross-sectional examination of socio-demographic and school-level correlates of
      children's school travel mode in Ottawa, Canada.
AB  - BACKGROUND: Active school transport (AST) is an important source of children's
      daily physical activity (PA). However, decreasing rates of AST have been reported
      in multiple countries during the last decades. The purpose of the present study
      was to examine the socio-demographic and school-level correlates of AST. METHODS:
      A stratified sample of children (N = 567, mean age = 10.0 years; 57.8% female)
      was recruited in the Ottawa area. Four sources of data were used for analyses: 1)
      child questionnaire including questions on school travel mode and time; 2) parent
      questionnaire providing information on household socio-demographic
      characteristics; 3) school administrator survey assessing school policies and
      practices pertaining to PA; and 4) school site audit performed by the study team.
      Generalized linear mixed models were used to identify socio-demographic and
      school-level correlates of AST while controlling for school clustering. RESULTS:
      Individual factors associated with higher odds of AST were male gender (OR =
      1.99; 95% CI = 1.30-3.03), journey time <5 minutes vs. >15 minutes (OR = 2.26;
      95% CI = 1.17-4.37), and 5-15 minutes vs. >15 minutes (OR = 2.27; 95% CI = 1.27
      4.03). Children were more likely to engage in AST if school administrators
      reported that crossing guards were employed (OR = 2.29; 95% CI = 1.22-4.30), or
      if they expressed major or moderate concerns about crime in the school
      neighbourhood (OR = 3.34; 95% CI = 1.34-8.32). In schools that identified safe
      routes to school and where traffic calming measures were observed, children were
      much more likely to engage in AST compared to schools without these features (OR
      = 7.87; 95% CI = 2.85-21.76). Moreover, if only one of these features was
      present, this was not associated with an increased likelihood of AST. CONCLUSION:
      These findings suggest that providing crossing guards may facilitate AST.
      Additionally, there was a synergy between the identification of safe routes to
      school and the presence of traffic calming measures, suggesting that these
      strategies should be used in combination.

PMID- 24886212
TI  - Cytokine profiles amongst Sudanese patients with visceral leishmaniasis and
      malaria co-infections.
AB  - BACKGROUND: The immune system plays a critical role in the development of co
      infections, promoting or preventing establishment of multiple infections and
      shaping the outcome of pathogen-host interactions. Its ability to mediate the
      interplay between visceral leishmaniasis (VL) and malaria has been suggested, but
      poorly documented. The present study investigated whether concomitant infection
      with Leishmania donovani complex and Plasmodium falciparum in naturally co
      infected patients altered the immunological response elicited by the two
      pathogens individually. RESULTS: Circulating levels of interferon (IFN)-gamma,
      interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-17A and tumor necrosis
      factor (TNF) were assessed in sera of patients infected with active VL and/or
      malaria and healthy individuals from Gedarif State, Sudan. Comparative analysis
      of cytokine profiles from co- and mono-infected patients highlighted significant
      differences in the immune response mounted upon co-infection, confirming the
      ability of L. donovani and P. falciparum to mutually interact at the
      immunological level. Progressive polarization towards type-1 and pro-inflammatory
      cytokine patterns characterized the co-infected patients, whose response partly
      reflected the effect elicited by VL (IFN-gamma, TNF) and malaria (IL-2, IL-13),
      and partly resulted from a synergistic interaction of the two diseases upon each
      other (IL-17A). Significantly reduced levels of P. falciparum parasitaemia (P
      <0.01) were detected in the co-infected group as opposed to the malaria-only
      patients, suggesting either a protective or a non-detrimental effect of the co
      infection against P. falciparum infection. CONCLUSIONS: These findings suggest
      that a new immunological scenario may occur when L. donovani and P. falciparum co
      infect the same patient, with potential implications on the course and resolution
      of these diseases.

PMID- 24886213
TI  - A comparison of health status in patients meeting alternative definitions for
      chronic fatigue syndrome/myalgic encephalomyelitis.
AB  - BACKGROUND: Several diagnostic definitions are available for Chronic Fatigue
      Syndrome/Myalgic Encephalomyelitis (CFS/ME) that varies significantly in their
      symptom criteria. This pilot study was conducted to determine whether simple
      biological and clinical measures differed between CFS/ME patients meeting the
      1994 Centres for Disease Control and Prevention (CDC) criteria, the International
      Consensus Criteria (ICC), as well as healthy controls. METHODS: A total of 45
      CFS/ME patients and 30 healthy controls from the South East Queensland region of
      Australia provided a blood sample, reported on their current symptoms, as well as
      aspects of their physical and social health using the Short-Form Health Survey
      (SF-36), and the World Health Organisation Disability Adjustment Schedule 2.0
      (WHO DAS 2.0). Differences were examined using independent sample t-testing.
      RESULTS: Patients fulfilling the ICC definition reported significantly lower
      scores (p < 0.05) for physical functioning, physical role, bodily pain, and
      social functioning than those that only fulfilled the 1994 CDC definition. ICC
      patients reported significantly greater (p < 0.05) disability across all domains
      of the WHO DAS 2.0. CONCLUSIONS: These preliminary findings suggest that the ICC
      identifies a distinct subgroup found within patients complying with the 1994 CDC
      definition, with more severe impairment to their physical and social functioning.

PMID- 24886214
TI  - Software algorithm and hardware design for real-time implementation of new
      spectral estimator.
AB  - BACKGROUND: Real-time spectral analyzers can be difficult to implement for PC
      computer-based systems because of the potential for high computational cost, and
      algorithm complexity. In this work a new spectral estimator (NSE) is developed
      for real-time analysis, and compared with the discrete Fourier transform (DFT).
      METHOD: Clinical data in the form of 216 fractionated atrial electrogram
      sequences were used as inputs. The sample rate for acquisition was 977 Hz, or
      approximately 1 millisecond between digital samples. Real-time NSE power spectra
      were generated for 16,384 consecutive data points. The same data sequences were
      used for spectral calculation using a radix-2 implementation of the DFT. The NSE
      algorithm was also developed for implementation as a real-time spectral analyzer
      electronic circuit board. RESULTS: The average interval for a single real-time
      spectral calculation in software was 3.29 MUs for NSE versus 504.5 MUs for DFT.
      Thus for real-time spectral analysis, the NSE algorithm is approximately 150*
      faster than the DFT. Over a 1 millisecond sampling period, the NSE algorithm had
      the capability to spectrally analyze a maximum of 303 data channels, while the
      DFT algorithm could only analyze a single channel. Moreover, for the 8 second
      sequences, the NSE spectral resolution in the 3-12 Hz range was 0.037 Hz while
      the DFT spectral resolution was only 0.122 Hz. The NSE was also found to be
      implementable as a standalone spectral analyzer board using approximately 26
      integrated circuits at a cost of approximately $500. The software files used for
      analysis are included as a supplement, please see the Additional files 1 and 2.
      CONCLUSIONS: The NSE real-time algorithm has low computational cost and
      complexity, and is implementable in both software and hardware for 1 millisecond
      updates of multichannel spectra. The algorithm may be helpful to guide
      radiofrequency catheter ablation in real time.

PMID- 24886215
TI  - Development of an insecticidal nanoemulsion with Manilkara subsericea
      (Sapotaceae) extract.
AB  - BACKGROUND: Plants have been recognized as a good source of insecticidal agents,
      since they are able to produce their own defensives to insect attack. Moreover,
      there is a growing concern worldwide to develop pesticides with low impact to
      environment and non-target organisms. Hexane-soluble fraction from ethanolic
      crude extract from fruits of Manilkara subsericea and its triterpenes were
      considered active against a cotton pest (Dysdercus peruvianus). Several natural
      products with insecticidal activity have poor water solubility, including
      triterpenes, and nanotechnology has emerged as a good alternative to solve this
      main problem. On this context, the aim of the present study was to develop an
      insecticidal nanoemulsion containing apolar fraction from fruits of Manilkara
      subsericea. RESULTS: It was obtained a formulation constituted by 5% of oil
      (octyldodecyl myristate), 5% of surfactants (sorbitan monooleate/polysorbate 80),
      5% of apolar fraction from M. subsericea and 85% of water. Analysis of mean
      droplet diameter (155.2 +/- 3.8 nm) confirmed this formulation as a nanoemulsion.
      It was able to induce mortality in D. peruvianus. It was observed no effect
      against acetylcholinesterase or mortality in mice induced by the formulation,
      suggesting the safety of this nanoemulsion for non-target organisms. CONCLUSIONS:
      The present study suggests that the obtained O/A nanoemulsion may be useful to
      enhance water solubility of poor water soluble natural products with insecticidal
      activity, including the hexane-soluble fraction from ethanolic crude extract from
      fruits of Manilkara subsericea.

PMID- 24886217
TI  - Field demonstration of an instrument performing automatic classification of
      geologic surfaces.
AB  - This work presents a method with which to automate simple aspects of geologic
      image analysis during space exploration. Automated image analysis on board the
      spacecraft can make operations more efficient by generating compressed maps of
      long traverses for summary downlink. It can also enable immediate automatic
      responses to science targets of opportunity, improving the quality of targeted
      measurements collected with each command cycle. In addition, automated analyses
      on Earth can process large image catalogs, such as the growing database of Mars
      surface images, permitting more timely and quantitative summaries that inform
      tactical mission operations. We present TextureCam, a new instrument that
      incorporates real-time image analysis to produce texture-sensitive
      classifications of geologic surfaces in mesoscale scenes. A series of tests at
      the Cima Volcanic Field in the Mojave Desert, California, demonstrated mesoscale
      surficial mapping at two distinct sites of geologic interest.

PMID- 24886216
TI  - Functional annotation signatures of disease susceptibility loci improve SNP
      association analysis.
AB  - BACKGROUND: Genetic association studies are conducted to discover genetic loci
      that contribute to an inherited trait, identify the variants behind these
      associations and ascertain their functional role in determining the phenotype. To
      date, functional annotations of the genetic variants have rarely played more than
      an indirect role in assessing evidence for association. Here, we demonstrate how
      these data can be systematically integrated into an association study's analysis
      plan. RESULTS: We developed a Bayesian statistical model for the prior
      probability of phenotype-genotype association that incorporates data from past
      association studies and publicly available functional annotation data regarding
      the susceptibility variants under study. The model takes the form of a binary
      regression of association status on a set of annotation variables whose
      coefficients were estimated through an analysis of associated SNPs in the GWAS
      Catalog (GC). The functional predictors examined included measures that have been
      demonstrated to correlate with the association status of SNPs in the GC and some
      whose utility in this regard is speculative: summaries of the UCSC Human Genome
      Browser ENCODE super-track data, dbSNP function class, sequence conservation
      summaries, proximity to genomic variants in the Database of Genomic Variants and
      known regulatory elements in the Open Regulatory Annotation database, PolyPhen-2
      probabilities and RegulomeDB categories. Because we expected that only a fraction
      of the annotations would contribute to predicting association, we employed a
      penalized likelihood method to reduce the impact of non-informative predictors
      and evaluated the model's ability to predict GC SNPs not used to construct the
      model. We show that the functional data alone are predictive of a SNP's presence
      in the GC. Further, using data from a genome-wide study of ovarian cancer, we
      demonstrate that their use as prior data when testing for association is
      practical at the genome-wide scale and improves power to detect associations.
      CONCLUSIONS: We show how diverse functional annotations can be efficiently
      combined to create 'functional signatures' that predict the a priori odds of a
      variant's association to a trait and how these signatures can be integrated into
      a standard genome-wide-scale association analysis, resulting in improved power to
      detect truly associated variants.

PMID- 24886218
TI  - Readiness of district and regional hospitals in Burkina Faso to provide caesarean
      section and blood transfusion services: a cross-sectional study.
AB  - BACKGROUND: Health centres and hospitals play a crucial role in reducing maternal
      mortality and morbidity by offering respectively Basic Emergency Obstetric and
      Newborn Care (BEmONC) and Comprehensive Emergency Obstetric and Newborn Care
      (CEmONC). The readiness of hospitals to provide CEmONC depends on the
      availability of qualified human resources, infrastructure like surgical theatres,
      and supplies like drugs and blood for transfusion. We assessed the readiness of
      district and regional hospitals in Burkina Faso to provide two key CEmONC
      functions, namely caesarean section and blood transfusion. As countries conduct
      EmONC needs assessments it is critical to provide national and subnational data,
      e.g. on the distribution of EmONC facilities as well as on facilities lacking the
      selected signal functions, to support the planning process for upgrading
      facilities so that they are ready to provide CEmONC. METHODS: In a cross
      sectional study we assessed the availability of relevant health workers,
      obstetric guidelines, caesarean section and blood transfusion services and
      experience with quality assurance approaches across all forty-three (43) district
      and nine (9) regional hospitals. RESULTS: The indicator corresponding to one
      comprehensive emergency care unit for 500,000 inhabitants was not achieved in
      Burkina Faso. Physicians with surgical skills, surgical assistants and
      anaesthesiologist assistants are sufficiently available in only 51.2%, 88.3% and
      72.0% of district hospitals, respectively. Two thirds of regional and 20.9% of
      district hospitals had blood banks. Most district hospitals as opposed to only
      one third of regional hospitals had experience in maternal death reviews.
      CONCLUSIONS: Our findings suggest that only 27.8% of hospitals in Burkina Faso at
      the time of the study could continuously offer caesarean sections and blood
      transfusion services. Four years later, progress has likely been made but many
      challenges remain to be overcome. Information provided in this study can serve as
      a baseline for monitoring progress in district and regional hospitals.

PMID- 24886219
TI  - Sleep disturbances and quality of life in postoperative management after
      esophagectomy for esophageal cancer.
AB  - BACKGROUND: The aims of this prospective study were to analyze the predictors of
      postoperative sleep disturbance after esophagectomy for cancer and to identify
      patients at risk for postoperative hypnotic administration. METHODS: Sixty two
      consecutive patients who underwent cancer-related esophagectomy were enrolled in
      this study from May 2011 to February 2012. Data about perioperative management,
      postoperative complications, ICU stay, and vasopressor, hypnotic, and painkiller
      administration were retrieved. The EORTC QLQ-C30 was used and global quality of
      life (QL2 item) and sleep disturbance (SL item) were the primary endpoints.
      Univariate and multivariate analyses were performed. RESULTS: Postoperative
      request of hypnotics independently predicted bad quality of life outcome. Sleep
      disturbance after esophagectomy was independently predicted by the duration of
      dopamine infusion in the ICU and the daily request of benzodiazepines. Even in
      this case, only sleep disturbance at diagnosis revealed to be an independent
      predictor of hypnotic administration need. ROC curve analysis showed that sleep
      disturbance at diagnosis was a good predictor of benzodiazepine request (AUC =
      73%, P = 0.02). CONCLUSIONS: The use of vasopressors in the ICU affects sleep in
      the following postoperative period and the use of hypnotics is neither completely
      successful nor lacking in possible consequences. Sleep disturbance at diagnosis
      can successfully predict patients who can develop sleep disturbance during the
      postoperative period.

PMID- 24886220
TI  - Effectiveness of an improved road safety policy in Ethiopia: an interrupted time
      series study.
AB  - BACKGROUND: In recent years, there has been an increasing interest in
      implementing road safety policy by different low income countries. However; the
      evidence is scarce on its success in the reduction of crashes, injuries and
      deaths. This study was conducted to assess whether road crashes, injuries and
      fatalities was reduced following the road safety regulation introduced as of
      September 2007 by Oromia Regional State Transport Bureau. METHODS: Routine road
      traffic accident data for the year 2002-2011were collected from sixteen traffic
      police offices. Data on average daily vehicle flow was obtained from the
      Ethiopian Road Authority. Interrupted time series design using segmented linear
      regression model was applied to estimate the effect of an improved road safety
      policy. RESULTS: A total of 4,053 crashes occurred on Addis Ababa - Adama/Hawassa
      main road. Of these crashes, almost half 46.4% (1,880) were property damage,
      29.4% (1,193) were fatal and 24.2% (980) injury crashes, resulting 1,392
      fatalities and 1,749 injuries. There were statistically significant reductions in
      non-injury crashes and deaths. Non-injury crash was reduced by 19% and fatality
      by 12.4% in the first year of implementing the revised transport safety
      regulation. CONCLUSION: Although revised road safety policy helped in reducing
      motor vehicle crashes and associated fatalities, the overall incidence rate is
      still very high. Further action is required to avoid unnecessary loss of lives.

PMID- 24886221
TI  - The effects of salbutamol on epithelial ion channels depend on the etiology of
      acute respiratory distress syndrome but not the route of administration.
AB  - INTRODUCTION: We investigated the effects of intravenous and intratracheal
      administration of salbutamol on lung morphology and function, expression of ion
      channels, aquaporin, and markers of inflammation, apoptosis, and alveolar
      epithelial/endothelial cell damage in experimental pulmonary (p) and
      extrapulmonary (exp) mild acute respiratory distress syndrome (ARDS). METHODS: In
      this prospective randomized controlled experimental study, 56 male Wistar rats
      were randomly assigned to mild ARDS induced by either intratracheal (n = 28,
      ARDSp) or intraperitoneal (n = 28, ARDSexp) administration of E. coli
      lipopolysaccharide. Four animals with no lung injury served as controls (NI).
      After 24 hours, animals were anesthetized, mechanically ventilated in pressure
      controlled mode with low tidal volume (6 mL/kg), and randomly assigned to receive
      salbutamol (SALB) or saline 0.9% (CTRL), intravenously (i.v., 10 MUg/kg/h) or
      intratracheally (bolus, 25 MUg). Salbutamol doses were targeted at an increase of
      ~ 20% in heart rate. Hemodynamics, lung mechanics, and arterial blood gases were
      measured before and after (at 30 and 60 min) salbutamol administration. At the
      end of the experiment, lungs were extracted for analysis of lung histology and
      molecular biology analysis. Values are expressed as mean +/- standard deviation,
      and fold changes relative to NI, CTRL vs. SALB RESULTS: The gene expression of
      ion channels and aquaporin was increased in mild ARDSp, but not ARDSexp. In
      ARDSp, intravenous salbutamol resulted in higher gene expression of alveolar
      epithelial sodium channel (0.20 +/- 0.07 vs. 0.68 +/- 0.24, p < 0.001), aquaporin
      1 (0.44 +/- 0.09 vs. 0.96 +/- 0.12, p < 0.001) aquaporin-3 (0.31 +/- 0.12 vs.
      0.93 +/- 0.20, p < 0.001), and Na-K-ATPase-alpha (0.39 +/- 0.08 vs. 0.92 +/-
      0.12, p < 0.001), whereas intratracheal salbutamol increased the gene expression
      of aquaporin-1 (0.46 +/- 0.11 vs. 0.92 +/- 0.06, p < 0.001) and Na-K-ATPase-alpha
      (0.32 +/- 0.07 vs. 0.58 +/- 0.15, p < 0.001). In ARDSexp, the gene expression of
      ion channels and aquaporin was not influenced by salbutamol. Morphological and
      functional variables and edema formation were not affected by salbutamol in any
      of the ARDS groups, regardless of the route of administration. CONCLUSION:
      Salbutamol administration increased the expression of alveolar epithelial ion
      channels and aquaporin in mild ARDSp, but not ARDSexp, with no effects on lung
      morphology and function or edema formation. These results may contribute to
      explain the negative effects of beta2-agonists on clinical outcome in ARDS.

PMID- 24886222
TI  - Estimation of the transmission of foot-and-mouth disease virus from infected
      sheep to cattle.
AB  - The quantitative role of sheep in the transmission of foot-and-mouth disease
      virus (FMDV) is not well known. To estimate the role of sheep in the transmission
      of FMDV, a direct contact transmission experiment with 10 groups of animals each
      consisting of 2 infected lambs and 1 contact calf was performed. Secretions and
      excretions (oral swabs, blood, urine, faeces and probang samples) from all
      animals were tested for the presence of FMDV by virus isolation (VI) and/or RT
      PCR. Serum was tested for the presence of antibodies against FMDV. To estimate
      FMDV transmission, the VI, RT-PCR and serology results were used. The partial
      reproduction ratio R0p i.e. the average number of new infections caused by one
      infected sheep introduced into a population of susceptible cattle, was estimated
      using either data of the whole infection chain of the experimental epidemics (the
      transient state method) or the final sizes of the experimental epidemics (the
      final size method). Using the transient state method, R0p was estimated as 1.0
      (95% CI 0.2 - 6.0) using virus isolation results and 1.4 (95% CI 0.3 - 8.0) using
      RT-PCR results. Using the final size method, R0p was estimated as 0.9 (95% CI 0.2
      - 3.0). Finally, R0p was compared to the R0's obtained in previous transmission
      studies with sheep or cattle only. This comparison showed that the infectivity of
      sheep is lower than that of cattle and that sheep and cattle are similarly
      susceptible to FMD. These results indicate that in a mixed population of sheep
      and cattle, sheep play a more limited role in the transmission of FMDV than
      cattle.

PMID- 24886223
TI  - Impact of aesthetic restorative treatment on anterior teeth with fluorosis among
      residents of an endemic area in Brazil: intervention study.
AB  - BACKGROUND: Endemic dental fluorosis has already been described in some regions
      of the world. The aim of this study was to evaluate the functional and
      psychosocial impact of direct aesthetic restorative treatments in endemic
      fluorosis patients in the northern state of Minas Gerais, Brazil. Was a quasi
      experimental intervention study. METHODS: The reference population consisted of
      individuals between 9 and 27 years of age that were served by a project intended
      to recover the smiles of patients with severe fluorosis. The questionnaires were
      administered on two occasions, 24 months apart (before and after dental
      treatment). Initially, descriptive analyses were conducted. Prevalence and
      severity, as well as the extent of the functional and psychosocial impact of oral
      disorders were estimated based on the Oral Health Impact Profile instrument (OHIP
      14). Comparisons between baseline and follow-up and between treatment techniques
      were carried out using the McNemar, Wilcoxon, and Mann-Whitney tests. RESULTS:
      The study involved 53 individuals, with a mean age of 15.9 years, treated with
      microabrasion, dental composite, or a combination of both techniques. The
      treatments performed proved to be competent for reducing the functional and
      psychosocial impact of oral disorders as measured by the OHIP-14, pointing to the
      possibility of establishing protocols to be used in programs aimed at restoring
      the aesthetics and functionality of the anterior teeth in large populations.
      CONCLUSIONS: After performing the direct aesthetic restorative treatments in
      patients with endemic fluorosis, a significant improvement was observed in the
      prevalence and severity, as well as the extent of the functional and psychosocial
      impact of oral disorders.

PMID- 24886225
TI  - Effectiveness and cost-effectiveness of telehealthcare for chronic obstructive
      pulmonary disease: study protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: Several feasibility studies show promising results of telehealthcare
      on health outcomes and health-related quality of life for patients suffering from
      chronic obstructive pulmonary disease, and some of these studies show that
      telehealthcare may even lower healthcare costs. However, the only large-scale
      trial we have so far - the Whole System Demonstrator Project in England - has
      raised doubts about these results since it conclude that telehealthcare as a
      supplement to usual care is not likely to be cost-effective compared with usual
      care alone. METHODS/DESIGN: The present study is known as 'TeleCare North' in
      Denmark. It seeks to address these doubts by implementing a large-scale,
      pragmatic, cluster-randomized trial with nested economic evaluation. The purpose
      of the study is to assess the effectiveness and the cost-effectiveness of a
      telehealth solution for patients suffering from chronic obstructive pulmonary
      disease compared to usual practice. General practitioners will be responsible for
      recruiting eligible participants (1,200 participants are expected) for the trial
      in the geographical area of the North Denmark Region. Twenty-six municipality
      districts in the region define the randomization clusters. The primary outcomes
      are changes in health-related quality of life, and the incremental cost
      effectiveness ratio measured from baseline to follow-up at 12 months. Secondary
      outcomes are changes in mortality and physiological indicators (diastolic and
      systolic blood pressure, pulse, oxygen saturation, and weight). DISCUSSION: There
      has been a call for large-scale clinical trials with rigorous cost-effectiveness
      assessments in telehealthcare research. This study is meant to improve the
      international evidence base for the effectiveness and cost-effectiveness of
      telehealthcare to patients suffering from chronic obstructive pulmonary disease
      by implementing a large-scale pragmatic cluster-randomized clinical trial. TRIAL
      REGISTRATION: Clinicaltrials.gov, http://NCT01984840, November 14, 2013.

PMID- 24886224
TI  - Inhibition of calpain reduces oxidative stress and attenuates endothelial
      dysfunction in diabetes.
AB  - AIMS: The present study was to investigate the role of calpain in reactive oxygen
      species (ROS) production in endothelial cells and endothelium-dependent vascular
      dysfunction under experimental conditions of diabetes. METHODS AND RESULTS:
      Exposure to high glucose activated calpain, induced apoptosis and reduced nitric
      oxide (NO) production without changing eNOS protein expression, its
      phosphorylation and dimers formation in primary human umbilical vein endothelial
      cells (HUVECs). These effects of high glucose correlated with intracellular ROS
      production and mitochondrial superoxide generation. Selectively scavenging
      mitochondrial superoxide increased NO production in high glucose-stimulated
      HUVECs. Inhibition of calpain using over-expression of calpastatin or
      pharmacological calpain inhibitor prevented high glucose-induced ROS production,
      mitochondrial superoxide generation and apoptosis, which were concurrent with an
      elevation of NO production in HUVECs. In mouse models of streptozotocin-induced
      type-1 diabetes and OVE26 type-1 diabetic mice, calpain activation correlated
      with an increase in ROS production and peroxynitrite formation in aortas.
      Transgenic over-expression of calpastatin reduced ROS production and
      peroxynitrite formation in diabetic mice. In parallel, diabetes-induced reduction
      of endothelium-dependent relaxation in aortic ring was reversed by over
      expression of calpastatin in mouse models of diabetes. However, the protective
      effect of calpastatin on endothelium-dependent relaxation was abrogated by eNOS
      deletion in diabetic mice. CONCLUSIONS: This study suggests that calpain may play
      a role in vascular endothelial cell ROS production and endothelium-dependent
      dysfunction in diabetes. Thus, calpain may be an important therapeutic target to
      overcome diabetes-induced vascular dysfunction.

PMID- 24886226
TI  - Structural rearrangement accompanying the ultrafast electrocyclization reaction
      of a photochromic molecular switch.
AB  - Probing the structural rearrangement of a model photochromic molecular switch
      provides a window on the fundamental dynamics of electrocyclization reactions.
      Taking advantage of resonance-enhanced femtosecond stimulated Raman scattering
      (FSRS) with a broadly tunable Raman excitation wavelength, we selectively probe
      the competing dynamics of both the reactive and nonreactive conformers of a
      diarylethene (DAE) derivative that are simultaneously present in solution.
      Measurements that preferentially probe the electrocyclization (ring-closing)
      reaction of the reactive species reveal an unexpectedly slow nuclear
      rearrangement, stretching to tens of picoseconds, in striking contrast with the
      prompt electronic dynamics in the formation of the closed-ring isomer. The
      different results from transient electronic and vibrational spectroscopies
      reflect the different aspects of the reaction that are probed by each technique,
      depending on whether one considers the electronic state of the molecule or the
      structural rearrangement of the nuclei. Using a different Raman excitation
      wavelength selectively probes the picosecond-scale intersystem crossing dynamics
      of the nonreactive conformer, revealing the vibrational spectra of the singlet
      and triplet excited states for the first time. The present study paves the way to
      a more complete understanding of the structural mechanisms accompanying the
      reversible photochromic switching process. 

PMID- 24886227
TI  - Evaluation of a real world intervention using professional football players to
      promote a healthy diet and physical activity in children and adolescents from a
      lower socio-economic background: a controlled pretest-posttest design.
AB  - BACKGROUND: The increasing rates of obesity among children and adolescents,
      especially in those from lower socio-economic backgrounds, emphasise the need for
      interventions promoting a healthy diet and physical activity. The present study
      aimed to examine the effectiveness of the 'Health Scores!' program, which
      combined professional football player role models with a school-based program to
      promote a healthy diet and physical activity to socially vulnerable children and
      adolescents. METHODS: The intervention was implemented in two settings:
      professional football clubs and schools. Socially vulnerable children and
      adolescents (n = 165 intervention group, n = 440 control group, aged 10-14 year)
      provided self-reported data on dietary habits and physical activity before and
      after the four-month intervention. Intervention effects were evaluated using
      repeated measures analysis of variance. In addition, a process evaluation was
      conducted. RESULTS: No intervention effects were found for several dietary
      behaviours, including consumption of breakfast, fruit, soft drinks or sweet and
      savoury snacks. Positive intervention effects were found for self-efficacy for
      having a daily breakfast (p < 0.01), positive attitude towards vegetables
      consumption (p < 0.01) and towards lower soft drink consumption (p < 0.001). A
      trend towards significance (p < 0.10) was found for self-efficacy for reaching
      the physical activity guidelines. For sports participation no significant
      intervention effect was found. In total, 92 pupils completed the process
      evaluation, the feedback was largely positive. CONCLUSIONS: The 'Health Scores!'
      intervention was successful in increasing psychosocial correlates of a healthy
      diet and PA. The use of professional football players as a credible source for
      health promotion was appealing to socially vulnerable children and adolescents.

PMID- 24886228
TI  - Development of a questionnaire to evaluate practitioners' confidence and
      knowledge in primary care in managing chronic kidney disease.
AB  - BACKGROUND: In the UK, chronic disease, including chronic kidney disease (CKD) is
      largely managed in primary care. We developed a tool to assess practitioner
      confidence and knowledge in managing CKD compared to other chronic diseases. This
      questionnaire was part of a cluster randomised quality improvement interventions
      in chronic kidney disease (QICKD; ISRCTN56023731). METHODS: The questionnaire was
      developed by family physicians, primary care nurses, academics and renal
      specialists. We conducted three focus groups (n=7, 6, and 8) to refine the
      questionnaire using groups of general practitioners, practice nurses and trainees
      in general practice. We used paper based versions to develop the questionnaire
      and online surveys to test it. Practitioners in a group of volunteer, trial
      practices received the questionnaire twice. We measured its reliability using
      Cohen's Kappa (K). RESULTS: The practitioners in the focus groups reached a
      consensus as to the key elements to include in the instrument. We achieved a
      73.1% (n=57/78) initial response rate for our questionnaire; of these 57, 54
      completed the questionnaire a second time. Family physicians made up the largest
      single group of respondents (47.4%, n=27). Initial response showed more female
      (64.9%, n=37) than male (35.1%, n=20) respondents. The reliability results from
      retesting showed that there was moderate agreement (k>0.4) on all questions; with
      many showing substantial agreement (k>0.6). There was substantial agreement in
      the questions about loop diuretics (k=0.608, CI 0.432-0.784, p<0.001), confidence
      in managing hypertension (k=0.628, 95%CI 0.452-0.804, p<0.001), diastolic blood
      pressure treatment thresholds in CKD (k=0.608, 95%CI 0.436-0.780, p<0.001) and
      the rate of decline of eGFR that would prompt referral (k=0.764, 95%CI 0.603
      0.925, p<0.001). CONCLUSION: The QICKD-CCQ is a reliable instrument for measuring
      confidence and knowledge among primary care practitioners on CKD management in
      the context of UK primary care.

PMID- 24886229
TI  - Promoting medical students' reflection on competencies to advance a global health
      equities curriculum.
AB  - BACKGROUND: The move to frame medical education in terms of competencies - the
      extent to which trainees "can do" a professional responsibility - is congruent
      with calls for accountability in medical education. However, the focus on
      competencies might be a poor fit with curricula intended to prepare students for
      responsibilities not emphasized in traditional medical education. This study
      examines an innovative approach to the use of potential competency expectations
      related to advancing global health equity to promote students' reflections and to
      inform curriculum development. METHODS: In 2012, 32 medical students were
      admitted into a newly developed Global Health and Disparities (GHD) Path of
      Excellence. The GHD program takes the form of mentored co-curricular activities
      built around defined competencies related to professional development and
      leadership skills intended to ameliorate health disparities in medically
      underserved settings, both domestically and globally. Students reviewed the GHD
      competencies from two perspectives: a) their ability to perform the identified
      competencies that they perceived themselves as holding as they began the GHD
      program and b) the extent to which they perceived that their future career would
      require these responsibilities. For both sets of assessments the response scale
      ranged from "Strongly Disagree" to "Strongly Agree." Wilcoxon's paired T-tests
      compared individual students' ordinal rating of their current level of ability to
      their perceived need for competence that they anticipated their careers would
      require. Statistical significance was set at p < .01. RESULTS: Students' ratings
      ranged from "strongly disagree" to "strongly agree" that they could perform the
      defined GHD-related competencies. However, on most competencies, at least 50 % of
      students indicated that the stated competencies were beyond their present ability
      level. For each competency, the results of Wilcoxon paired T-tests indicate - at
      statistically significant levels - that students perceive more need in their
      careers for GHD-program defined competencies than they currently possess.
      CONCLUSION: This study suggests congruence between student and program
      perceptions of the scope of practice required for GHD. Students report the need
      for enhanced skill levels in the careers they anticipate. This approach to
      formulating and reflecting on competencies will guide the program's design of
      learning experiences aligned with students' career goals.

PMID- 24886230
TI  - Total parathyroidectomy with trace amounts of parathyroid tissue
      autotransplantation as the treatment of choice for secondary hyperparathyroidism:
      a single-center experience.
AB  - BACKGROUND: The aim of the study was to evaluate total parathyroidectomy with
      trace amounts of parathyroid tissue (30 mg) as a surgical option in secondary
      hyperparathyroidism (sHPT) treatment. METHODS: From January 2008 to March 2012,
      47 patients underwent parathyroidectomy. Comparisons of demographic data,
      symptoms, and preoperative or postoperative biochemistry were made between total
      parathyroidectomy with trace amounts of parathyroid tissue autotransplantation
      group and total parathyroidectomy group. RESULTS: Out of 47 cases, 45 had
      successful operation. 187 parathyroid glands identified at the initial operation
      were reported in 47 patients. 43 patients had been diagnosed with parathyroid
      hyperplasia, and 4 patients had a benign adenoma. After operation, pruritus, bone
      pain and muscle weakness disappeared, also serum PTH and serum phosphate were
      declined markedly as well. After discharge, two patients (in total
      parathyroidectomy group) were readmitted because of postoperative
      hypoparathyroidism. Graft-dependent recurrence was not observed in an average
      follow-up of 42 months. CONCLUSIONS: Total parathyroidectomy with
      sternocleidomastoid muscle trace amounts of parathyroid tissue
      autotransplantation is considered to be a feasible, safe and effective surgical
      option for the patients with sHPT.

PMID- 24886231
TI  - Lone workers attitudes towards their health: views of Ontario truck drivers and
      their managers.
AB  - BACKGROUND: Truck driving is the second most common occupation among Canadian
      men. Transportation of goods via roads is of crucial importance for the Canadian
      economy. The industry is responsible annually for $17 billion in GDP and is
      projected to increase by 28% over the next 10 years. Recruitment is an issue with
      20% of drivers projected to retire or leave the profession in the next 10 years.
      Despite the reliance on transport truck drivers for the delivery of goods which
      affects Canada's economy and daily living of residents, little is known about the
      health care needs of this large cohort of primarily male lone workers from a
      drivers' perspective. Transport truck drivers are independent workers whose non
      traditional workplace is their tractor, the truck stops and the journey on the
      road.The objective of this study was to obtain a contextually informed
      description of lifestyle issues, health and disease risk factors experienced by
      drivers and perceived by their managers in the truck driving occupation. METHODS:
      Using a grounded theory approach, 4 focus groups were conducted with drivers (n =
      16) and managers (n = 10) from two trucking companies in Southwestern Ontario to
      identify the lived experience of the drivers as it relates to preventable risks
      to health and wellness. A semi structured guided interview was used to explore
      the lifestyle context of transport truck driving and organizational aspects of
      the occupation (workplace culture, working conditions and health and wellness
      promotion). RESULTS: The predominant themes described stress, workplace,
      communication, lifestyle, driving culture, family, and fatigue concerns. In terms
      of the transportation work environment, drivers and managers were aware of the
      profession's potential to foster lifestyle related chronic diseases but described
      challenges in making the profession more amenable to a healthy lifestyle.
      CONCLUSIONS: Workplace environmental determinants are significant in shaping
      health behaviours. Chronic disease health risks were the main health concerns
      identified. Health risks were exacerbated by working conditions (job demands,
      work hours, financial pressure and the sedentary nature of the job). Workplace
      health strategies will need to take into account the unique challenges of the
      occupation.

PMID- 24886232
TI  - Factors associated with the goal of treatment in the last week of life in old
      compared to very old patients: a population-based death certificate survey.
AB  - BACKGROUND: Little is known about the type of care older people of different ages
      receive at the end of life. The goal of treatment is an important parameter of
      the quality of end-of-life care. This study aims to provide an evaluation of the
      main goal of treatment in the last week of life of people aged 86 and older
      compared with those between 75 and 85 and to examine how treatment goals are
      associated with age. METHODS: Population- based cross sectional survey in
      Flanders, Belgium. A stratified random sample of death certificates was drawn of
      people who died between 1 June and 30 November 2007. The effective study sample
      included 3,623 deaths (response rate: 58.4%). Non-sudden deaths of patients aged
      75 years and older were selected (N = 1681). Main outcome was the main goal of
      treatment in the last week of life (palliative care or life-prolonging/curative
      treatment). RESULTS: In patients older than 75, the main goal of treatment in the
      last week was in the majority of cases palliative care (77.9%). Patients between
      75 and 85 more often received life-prolonging/curative treatment than older
      patients (26.6% vs. 15.8%). Most patient and health care characteristics are
      similarly related to the main goal of treatment in both age groups. The patient's
      age was independently related to having comfort care as the main goal of
      treatment. The main goal of treatment was also independently associated with the
      patient's sex, cause and place of death and the time already in treatment.
      CONCLUSION: Age is independently related to the main goal of treatment in the
      last week of life with people over 85 being more likely to receive palliative
      care and less likely to receive curative/life-prolonging treatment compared with
      those aged 75-85. This difference could be due to the patient's wishes but could
      also be the result of the attitudes of care givers towards the treatment of older
      people.

PMID- 24886233
TI  - The PROTECCT-M study: a cohort study investigating associations between novel
      specific biomarkers, patient-related, healthcare system markers and the
      trajectory of COPD patients treated in primary care.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is the most common
      severe chronic disease in primary care. It is typically diagnosed at a late
      stage, and it is also difficult to predict its trajectory and hence to tailor
      treatment and rehabilitation. The overall aim is to study determinants of
      exacerbations of COPD treated in primary care and to study, if the prognosis is
      related to patient-related, healthcare system markers or levels of the potential
      biomarkers such as microfibrillar-associated protein 4 (MFAP4) and surfactant
      protein D (SP-D). Furthermore, we aim to establish a cohort of COPD patients
      treated in Danish primary care comprising register data, data captured from the
      GPs' electronic patient record system (EPR) and a biobank in order to make
      analyses on factors associated with different tractories of COPD treated in
      primary care. METHODS/DESIGN: A cohort study of incident and prevalent COPD
      patients treated and followed by their GPs using data capture, which is a
      computer system collecting data from the GPs' own EPR and transferring them to
      the Danish General Practice Research Database. The participating COPD patients
      were investigated at a baseline consultation by their own GP, and the results
      were registered using a pop-up menu by the GP. During the consultation blood
      samples were taken and the patients were given a questionnaire. The patients will
      then be followed prospectively at yearly consultations and in between these
      consultations by means of the data capture system. The collected data will also
      be combined with register data from other sources. The data collection started in
      December 2012, and so far 30 practices with 77 GPs have included about 350
      patients. The study aims to include 2000 patients till the end of 2016, and after
      that to continue to collect data on these patients using the data capture system.
      DISCUSSION: The GP currently lacks tools to predict trajectory of their COPD
      patients. The measurement of lung function only reflects loss of lung capacity
      and not disease activity. Use of biomarkers for detection of early COPD could be
      a possible way of predicting trajectory to aid both the GP and his/her patients.
      This study aims to provide evidence of determinants of a COPD trajectory,
      including novel specific biomarkers and other patient- and healthcare system
      related markers. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration
      System, Identifier: NCT01698151.

PMID- 24886234
TI  - Recurrent right ventricular cardiac myxoma in a patient with Carney complex: a
      case report.
AB  - INTRODUCTION: Carney complex is a multiple neoplasia syndrome involving cardiac,
      endocrine, neural and cutaneous tumors with a variety of pigmented skin lesions.
      It has an autosomal dominant mode of inheritance. Approximately 7% of cardiac
      myxomas are related to the Carney complex. Myxomas that occur as part of the
      Carney complex affect both sexes with equal frequency. Cardiac myxomas with
      Carney complex are reported mostly in the left side of the heart and are less
      common on the right side. As per our review, this is the first reported case of
      Carney complex with right ventricle cardiac myxoma. CASE PRESENTATION: We present
      a rare case of recurrent cardiac myxoma in a patient later diagnosed to have
      Carney complex. A 46-year-old Caucasian man with a history of thyroid hyperplasia
      came to out-patient cardiology department with new onset atrial fibrillation. A
      transthoracic echocardiogram revealed a right ventricular mass attached to his
      interventricular septum, which was later seen on a transesophageal echocardiogram
      and cardiac magnetic resonance imaging. He underwent resection of the ventricular
      mass which on pathology revealed myxoma. He later developed skin lesions,
      pituitary adenoma and Sertoli cell tumor suggesting Carney complex. Two years
      later he developed a new mass within his right atrium which was later resected.
      CONCLUSIONS: Carney complex is a rare autosomal dominant disease with variable
      penetrance. Since it involves multiple organs, patients diagnosed with Carney
      complex should undergo serial endocrine workup, neural assessments,
      echocardiograms and testicular ultrasounds. Of the total number of cases of
      Carney complex, 65% are linked to PRKAR1A gene mutation. It is important for
      clinicians to be cognizant of a link between cardiac myxoma and Carney complex.
      The use of multi-imaging modalities allows better delineation of the mass before
      planned resection. Carney complex-related cardiac myxoma comprises 7% of all
      cardiac myxomas. Right ventricular cardiac myxomas are rare. This case report is
      the first to describe right ventricular myxoma with Carney complex.

PMID- 24886235
TI  - A multi-site single-blind clinical study to compare the effects of STAIR
      Narrative Therapy to treatment as usual among women with PTSD in public sector
      mental health settings: study protocol for a randomized controlled trial.
AB  - BACKGROUND: This article provides a description of the rationale, design, and
      methods of a multisite clinical trial which evaluates the potential benefits of
      an evidence-based psychosocial treatment, STAIR Narrative Therapy, among women
      with posttraumatic stress disorder (PTSD) related to interpersonal violence who
      are seeking services in public sector community mental health clinics. This is
      the first large multisite trial of an evidence-based treatment for PTSD provided
      in the context of community settings that are dedicated to the treatment of
      poverty-level patient populations. METHODS: The study is enrolling 352
      participants in a minimum of 4 community clinics. Participants are randomized
      into either STAIR Narrative Therapy or Treatment As Usual (TAU). Primary outcomes
      are PTSD, emotion management and interpersonal problems. The study will allow a
      flexible application of the protocol determined by patient need and preferences.
      Secondary analyses will assess the relationship of outcomes to different patterns
      of treatment implementation for different levels of baseline symptom severity.
      DISCUSSION: The article discusses the rationale and study issues related to the
      use of a flexible delivery of a protocol treatment and of the selection of
      treatment as it is actually practiced in the community as the comparator. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier: NCT01488539.

PMID- 24886236
TI  - Analysis of trend of malaria prevalence in south-west Ethiopia: a retrospective
      comparative study.
AB  - BACKGROUND: The temporal analysis of pertinent malaria data on the health care
      system is crucially important to measure success or failure of malaria programmes
      and identify remaining malaria hot spots. The objectives of this study were to
      analyse and compare trends of malaria prevalence around Gilgel-Gibe Hydroelectric
      Dam (GGHD), and a control site over an eight-year period. METHODS: A
      retrospective record review of health care services was conducted in southwest
      Ethiopia. Records of malaria cases over an eight-year period in primary health
      care units of two localities were reviewed. One study site was selected from
      villages around a man-made lake, GGHD, within a distance of 10 km, and a control
      site with similar geographic features was identified. Data were summarized in
      tables; prevalence of malaria was analysed and described by person, place and
      time using line graphs. Odds ratio was used to examine significant difference of
      malaria occurrence in the two sites. RESULTS: Records of 163,918 malaria cases
      registered over eight years (September 2003 to August 2011) were explored. Close
      to one thirds (32.7%) of these cases were from GGHD site and two-thirds (67.3%)
      of them were from the control site. Among the confirmed cases, Plasmodium
      falciparum constituted 54.6%, Plasmodium vivax accounted for 41.6%, and mixed
      infection was 3.8%. There were three peaks of malaria prevalence in the control
      site whereas only one major peak was identified during the eight-year period in
      GGHD site; and prevalence of malaria in GGHD site was lower than control site.
      Children in the age range ten to 14 years were the most affected by the disease,
      followed by children below the age group five to nine years, which demands due
      consideration in the effort of malaria control. CONCLUSIONS: More malaria
      prevalence was observed in the control site compared to GGHD site almost
      throughout the time period considered. The present finding did not show evidence
      of the excess malaria burden in the GGHD site due to the presence of the dam.

PMID- 24886237
TI  - A whole genome SNP genotyping by DNA microarray and candidate gene association
      study for kidney stone disease.
AB  - BACKGROUND: Kidney stone disease (KSD) is a complex disorder with unknown
      etiology in majority of the patients. Genetic and environmental factors may cause
      the disease. In the present study, we used DNA microarray to genotype single
      nucleotide polymorphisms (SNP) and performed candidate gene association analysis
      to determine genetic variations associated with the disease. METHODS: A whole
      genome SNP genotyping by DNA microarray was initially conducted in 101 patients
      and 105 control subjects. A set of 104 candidate genes reported to be involved in
      KSD, gathered from public databases and candidate gene association study
      databases, were evaluated for their variations associated with KSD. RESULTS:
      Altogether 82 SNPs distributed within 22 candidate gene regions showed
      significant differences in SNP allele frequencies between the patient and control
      groups (P < 0.05). Of these, 4 genes including BGLAP, AHSG, CD44, and HAO1,
      encoding osteocalcin, fetuin-A, CD44-molecule and glycolate oxidase 1,
      respectively, were further assessed for their associations with the disease
      because they carried high proportion of SNPs with statistical differences of
      allele frequencies between the patient and control groups within the gene. The
      total of 26 SNPs showed significant differences of allele frequencies between the
      patient and control groups and haplotypes associated with disease risk were
      identified. The SNP rs759330 located 144 bp downstream of BGLAP where it is a
      predicted microRNA binding site at 3'UTR of PAQR6 - a gene encoding progestin and
      adipoQ receptor family member VI, was genotyped in 216 patients and 216 control
      subjects and found to have significant differences in its genotype and allele
      frequencies (P = 0.0007, OR 2.02 and P = 0.0001, OR 2.02, respectively).
      CONCLUSIONS: Our results suggest that these candidate genes are associated with
      KSD and PAQR6 comes into our view as the most potent candidate since associated
      SNP rs759330 is located in the miRNA binding site and may affect mRNA expression
      level.

PMID- 24886238
TI  - An equivalence evaluation of a nurse-moderated group-based internet support
      program for new mothers versus standard care: a pragmatic preference randomised
      controlled trial.
AB  - BACKGROUND: All mothers in South Australia are offered a clinic or home-visit by
      a Child and Family Health community nurse in the initial postnatal weeks.
      Subsequent support is available on request from staff in community clinics and
      from a telephone helpline. The aim of the present study is to compare equivalence
      of a single clinic-based appointment plus a nurse-moderated group-based internet
      intervention when infants were aged 0-6 months versus a single home-visit
      together with subsequent standard services (the latter support was available to
      mothers in both study groups). METHODS/DESIGN: The evaluation utilised a
      pragmatic preference randomised trial comparing the equivalence of outcomes for
      mothers and infants across the two study groups. Eligible mothers were those
      whose services were provided by nurses working in one of six community clinics in
      the metropolitan region of Adelaide. Mothers were excluded if they did not have
      internet access, required an interpreter, or their nurse clinician recommended
      that they not participate due to issues such as domestic violence or substance
      abuse. Randomisation was based on the service identification number sequentially
      assigned to infants when referred to the Child and Family Health Services from
      birthing units (this was done by administrative staff who had no involvement in
      recruiting mothers, delivering the intervention, or analyzing results for the
      study). Consistent with design and power calculations, 819 mothers were recruited
      to the trial. The primary outcomes for the trial are parents' sense of competence
      and self-efficacy measured using standard self-report questionnaires. Secondary
      outcomes include the quality of mother-infant relationships, maternal social
      support, role satisfaction and maternal mental health, infant social-emotional
      and language development, and patterns of service utilisation. Maternal and
      infant outcomes will be evaluated using age-appropriate questionnaires when
      infants are aged <2 months (pre-intervention), 9, 15, and 21 months. DISCUSSION:
      We know of no previous study that has evaluated an intervention that combines the
      capacity of nurse and internet-based services to improve outcomes for mothers and
      infants. The knowledge gained from this study will inform the design and conduct
      of community-based postnatal mother and child support programs. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12613000204741.

PMID- 24886239
TI  - Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and
      pathogenesis in a mouse model of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) pathology occurs in part as the result of
      excessive production of beta-amyloid (Abeta). Metabotropic glutamate receptor 5
      (mGluR5) is now considered a receptor for Abeta and consequently contributes to
      pathogenic Abeta signaling in AD. RESULTS: Genetic deletion of mGluR5 rescues the
      spatial learning deficits observed in APPswe/PS1DeltaE9 AD mice. Moreover, both
      Abeta oligomer formation and Abeta plaque number are reduced in APPswe/PS1DeltaE9
      mice lacking mGluR5 expression. In addition to the observed increase in Abeta
      oligomers and plaques in APPswe/PS1DeltaE9 mice, we found that both mTOR
      phosphorylation and fragile X mental retardation protein (FMRP) expression were
      increased in these mice. Genetic deletion of mGluR5 reduced Abeta oligomers,
      plaques, mTOR phosphorylation and FMRP expression in APPswe/PS1DeltaE9 mice.
      CONCLUSIONS: Thus, we propose that Abeta activation of mGluR5 appears to initiate
      a positive feedback loop resulting in increased Abeta formation and AD pathology
      in APPswe/PS1DeltaE9 mice via mechanism that is regulated by FMRP.

PMID- 24886241
TI  - Effects of short-term radiation emitted by WCDMA mobile phones on teenagers and
      adults.
AB  - BACKGROUND: With the rapid increasing use of third generation (3 G) mobile
      phones, social concerns have arisen concerning the possible health effects of
      radio frequency-electromagnetic fields (RF-EMFs) emitted by wideband code
      division multiple access (WCDMA) mobile phones in humans. The number of people,
      who complain of various symptoms such as headache, dizziness, and fatigue, has
      also increased. Recently, the importance of researches on teenagers has been on
      the rise. However, very few provocation studies have examined the health effects
      of WCDMA mobile phone radiation on teenagers. METHODS: In this double-blind
      study, two volunteer groups of 26 adults and 26 teenagers were simultaneously
      investigated by measuring physiological changes in heart rate, respiration rate,
      and heart rate variability for autonomic nervous system (ANS), eight subjective
      symptoms, and perception of RF-EMFs during sham and real exposure sessions to
      verify its effects on adults and teenagers. Experiments were conducted using a
      dummy phone containing a WCDMA module (average power, 250 mW at 1950 MHz;
      specific absorption rate, 1.57 W/kg) within a headset placed on the head for 32
      min. RESULTS: Short-term WCDMA RF-EMFs generated no significant changes in ANS,
      subjective symptoms or the percentages of those who believed they were being
      exposed in either group. CONCLUSIONS: Considering the analyzed physiological
      data, the subjective symptoms surveyed, and the percentages of those who believed
      they were being exposed, 32 min of RF radiation emitted by WCDMA mobile phones
      demonstrated no effects in either adult or teenager subjects.

PMID- 24886240
TI  - The prevalence and burden of subthreshold generalized anxiety disorder: a
      systematic review.
AB  - BACKGROUND: To review the prevalence and impact of generalized anxiety disorder
      (GAD) below the diagnostic threshold and explore its treatment needs in times of
      scarce healthcare resources. METHODS: A systematic literature search was
      conducted until January 2013 using PUBMED/MEDLINE, PSYCINFO, EMBASE and reference
      lists to identify epidemiological studies of subthreshold GAD, i.e. GAD symptoms
      that do not reach the current thresholds of DSM-III-R, DSM-IV or ICD-10. Quality
      of all included studies was assessed and median prevalences of subthreshold GAD
      were calculated for different subpopulations. RESULTS: Inclusion criteria led to
      15 high-quality and 3 low-quality epidemiological studies with a total of 48,214
      participants being reviewed. Whilst GAD proved to be a common mental health
      disorder, the prevalence for subthreshold GAD was twice that for the full
      syndrome. Subthreshold GAD is typically persistent, causing considerably more
      suffering and impairment in psychosocial and work functioning, benzodiazepine and
      primary health care use, than in non-anxious individuals. Subthreshold GAD can
      also increase the risk of onset and worsen the course of a range of comorbid
      mental health, pain and somatic disorders; further increasing costs. Results are
      robust against bias due to low study quality. CONCLUSIONS: Subthreshold GAD is a
      common, recurrent and impairing disease with verifiable morbidity that claims
      significant healthcare resources. As such, it should receive additional research
      and clinical attention.

PMID- 24886242
TI  - Treatment of acute pancreatitis with protease inhibitors administered through
      intravenous infusion: an updated systematic review and meta-analysis.
AB  - BACKGROUND: The intravenous use of protease inhibitors in patients with acute
      pancreatitis is still controversial. The purpose of this study was to evaluate
      the effectiveness of protease inhibitors intravenously administered to prevent
      pancreatitis-associated complications. METHODS: We updated our previous meta
      analysis with articles of randomized controlled trials published from January
      1965 to March 2013 on the effectiveness of protease inhibitors for acute
      pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and
      Japana Centra Revuo Medicina was conducted. In addition, Internet-based
      registries (ClinicalTrials.gov, controlled-trials.com, UMIN, JMACCT, and JAPIC)
      were used to search for on-going clinical trials. Furthermore, references of
      review articles and previously published meta-analyses were handsearched. The
      main outcome of interest was the overall mortality rate from acute pancreatitis.
      RESULTS: Seventeen trials were selected for analysis. Overall, protease
      inhibitors did not achieve a significant risk reduction in mortality (pooled risk
      difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number
      needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in
      moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10)
      did not show a significant effect of protease inhibitors to prevent death (pooled
      RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An
      additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality)
      revealed a significant risk reduction. CONCLUSION: The present meta-analysis re
      confirmed that there is no solid evidence that supports the intravenous use of
      protease inhibitors to prevent death due to acute pancreatitis.

PMID- 24886243
TI  - A cross-sectional analysis of the effects of residential greenness on blood
      pressure in 10-year old children: results from the GINIplus and LISAplus studies.
AB  - BACKGROUND: According to Ulrich's psychoevolutionary theory, contact with green
      environments mitigates stress by activating the parasympathetic system,
      (specifically, by decreasing blood pressure (BP)). Experimental studies have
      confirmed this biological effect. However, greenness effects on BP have not yet
      been explored using an observational study design. We assessed whether
      surrounding residential greenness is associated with BP in 10 year-old German
      children. METHODS: Systolic and diastolic BPs were assessed in 10 year-old
      children residing in the Munich and Wesel study areas of the German GINIplus and
      LISAplus birth cohorts. Complete exposure, outcome and covariate data were
      available for 2,078 children. Residential surrounding greenness was defined as
      the mean of Normalized Difference Vegetation Index (NDVI) values, derived from
      Landsat 5 TM satellite images, in circular 500-m buffers around current home
      addresses of participants. Generalized additive models assessed pooled and area
      specific associations between BP and residential greenness categorized into area
      specific tertiles. RESULTS: In the pooled adjusted model, the systolic BP of
      children living at residences with low and moderate greenness was 0.90 +/- 0.50
      mmHg (p-value = 0.073) and 1.23 +/- 0.50 mmHg (p-value = 0.014) higher,
      respectively, than the systolic BP of children living in areas of high greenness.
      Similarly, the diastolic BP of children living in areas with low and moderate
      greenness was 0.80 +/- 0.38 mmHg (p-value = 0.033) and 0.96 +/- 0.38 mmHg (p
      value = 0.011) higher, respectively, than children living in areas with high
      greenness. These associations were not influenced by environmental stressors
      (temperature, air pollution, noise annoyance, altitude and urbanisation level).
      When stratified by study area, associations were significant among children
      residing in the urbanised Munich area but null for those in the rural Wesel area.
      CONCLUSIONS: Lower residential greenness was positively associated with higher BP
      in 10 year-old children living in an urbanised area. Further studies varying in
      participants' age, geographical area and urbanisation level are required.

PMID- 24886244
TI  - Benign infantile convulsion as a diagnostic clue of paroxysmal kinesigenic
      dyskinesia: a case series.
AB  - INTRODUCTION: Paroxysmal kinesigenic dyskinesia is characterized by sudden
      attacks of involuntary movements. It is often misdiagnosed clinically as
      psychogenic illness, which distresses the patients to a great extent. A correct
      diagnosis will improve the quality of life in patients with paroxysmal
      kinesigenic dyskinesia because treatment with low doses of anticonvulsants is
      effective for eliminating the clinical manifestations. Paroxysmal kinesigenic
      dyskinesia can occur independently of or concurrently with benign infantile
      convulsion. Identification of PRRT2 as the causative gene of benign infantile
      convulsion and paroxysmal kinesigenic dyskinesia allows genetic confirmation of
      the clinical diagnosis. CASE PRESENTATION: We describe the clinical features of a
      Japanese family with either paroxysmal kinesigenic dyskinesia or benign infantile
      convulsion. A PRRT2 missense mutation (c.981C > G, p.Ile327Met) was identified in
      two patients with benign infantile convulsion and three patients with paroxysmal
      kinesigenic dyskinesia as well as in two unaffected individuals. Allowing
      incomplete penetrance in the mutation carriers, this mutation co-segregated
      completely with the phenotype. The patients with paroxysmal kinesigenic
      dyskinesia had been misdiagnosed with psychogenic illness for many years. They
      were correctly diagnosed with paroxysmal kinesigenic dyskinesia when their
      children visited a pediatrician for benign infantile convulsion. Treatment with
      carbamazepine controlled their involuntary movements completely. CONCLUSIONS:
      Paroxysmal kinesigenic dyskinesia is a treatable movement disorder that is often
      misdiagnosed clinically as psychogenic illness. It is important to note that two
      clinically distinct disorders, benign infantile convulsion and paroxysmal
      kinesigenic dyskinesia, are allelic conditions caused by PRRT2 mutations.
      Paroxysmal kinesigenic dyskinesia should be suspected in families with a child
      with benign infantile convulsion.

PMID- 24886247
TI  - The performance of sequence symmetry analysis as a tool for post-market
      surveillance of newly marketed medicines: a simulation study.
AB  - BACKGROUND: Sequence symmetry analysis (SSA) is a potential tool for rapid
      detection of adverse drug events (ADRs) associated with newly marketed medicines
      utilizing computerized claims data. SSA is robust to patient specific confounders
      but it is sensitive to the underlying utilization trends in the medicines of
      interest. Methods to adjust for utilisation trends have been developed, however,
      there has been no systematic investigation to assess the performance of SSA when
      variable prescribing trends occur. The objective of this study was to evaluate
      the validity of SSA as a signal detection tool for newly marketed medicines.
      METHODS: Randomly simulated prescription supplies for a population of 1 million
      were generated for two medicines, DrugA (medicine of interest) and DrugB
      (medicine indicative of an adverse event). Scenarios were created by varying
      medicine utilization trends for a newly marketed medicine (DrugA). In addition,
      the magnitude of association between DrugA and DrugB was varied. For each
      scenario 1000 simulations were generated. Average Adjusted Sequence Ratios (ASR),
      bootstrapped 95% confidence intervals (CIs), percentage of CI's which covered the
      expected ASR and percent relative bias were calculated. RESULTS: When no
      association was simulated between DrugA and DrugB, over 95% of SSA CI's covered
      the expected ASR (ASR = 1) and relative bias was 1% or less irrespective of
      medicine utilization trends. In scenarios where DrugA and DrugB were associated
      (ASR = 2), unadjusted SR's were underestimated by between 11.7 and 15.3%. After
      adjustment for trend, ASR estimates were close to expected with relative bias
      less than 1%. Power was over 80% in all scenarios except for one scenario in
      which medicine uptake was gradual and the effect of interest was weak (ASR =
      1.2). CONCLUSIONS: Adjustment for underlying medicine utilization patterns
      effectively overcomes potential under-ascertainment bias in SSA analyses. SSA may
      be effectively applied as a safety signal detection tool for newly marketed
      medicines where sufficiently large health claim data are available.

PMID- 24886246
TI  - Preventing the development of depression at work: a systematic review and meta
      analysis of universal interventions in the workplace.
AB  - BACKGROUND: Depression is a major public health problem among working-age adults.
      The workplace is potentially an important location for interventions aimed at
      preventing the development of depression, but to date, the mental health impact
      of universal interventions in the workplace has been unclear. METHOD: A
      systematic search was conducted in relevant databases to identify randomized
      controlled trials of workplace interventions aimed at universal prevention of
      depression. The quality of studies was assessed using the Downs and Black
      checklist. A meta-analysis was performed using results from studies of adequate
      methodological quality, with pooled effect size estimates obtained from a random
      effects model. RESULTS: Nine workplace-based randomized controlled trials (RCT)
      were identified. The majority of the included studies utilized cognitive
      behavioral therapy (CBT) techniques. The overall standardized mean difference
      (SMD) between the intervention and control groups was 0.16 (95% confidence
      interval (CI): 0.07, 0.24, P = 0.0002), indicating a small positive effect. A
      separate analysis using only CBT-based interventions yielded a SMD of 0.12 (95%
      CI: -0.01, 0.24, P = 0.07). [corrected]. CONCLUSIONS: There is good quality
      evidence that universally delivered workplace mental health interventions can
      reduce the level of depression symptoms among workers. There is more evidence for
      the effectiveness of CBT-based programs than other interventions. Evidence-based
      workplace interventions should be a key component of efforts to prevent the
      development of depression among adults.

PMID- 24886245
TI  - Acylglycerol kinase promotes cell proliferation and tumorigenicity in breast
      cancer via suppression of the FOXO1 transcription factor.
AB  - BACKGROUND: Acylglycerol kinase (AGK) is reported to be overexpressed in multiple
      cancers. The clinical significance and biological role of AGK in breast cancer,
      however, remain to be established. METHODS: AGK expression in breast cancer cell
      lines, paired patient tissues were determined using immunoblotting and Real-time
      PCR. 203 human breast cancer tissue samples were analyzed by immunochemistry
      (IHC) to investigate the relationship between AGK expression and the
      clinicopathological features of breast cancer. Functional assays, such as colony
      formation, anchorage-independent growth and BrdU assay, and a xenograft tumor
      model were used to determine the oncogenic role of AGK in human breast cancer
      progression. The effect of AGK on FOXO1 transactivity was further investigated
      using the luciferase reporter assays, and by detection of the FOXO1 downstream
      genes. RESULTS: Herein, we report that AGK was markedly overexpressed in breast
      cancer cells and clinical tissues. Immunohistochemical analysis showed that the
      expression of AGK significantly correlated with patients' clinicopathologic
      characteristics, including clinical stage and tumor-nodule-metastasis (TNM)
      classification. Breast cancer patients with higher levels of AGK expression had
      shorter overall survival compared to patients with lower AGK levels. We gained
      valuable insights into the mechanism of AGK expression in breast cancer cells by
      demonstrating that overexpressing AGK significantly enhanced, whereas silencing
      endogenous AGK inhibited, the proliferation and tumorigenicity of breast cancer
      cells both in vitro and in vivo. Furthermore, overexpression of AGK enhanced G1-S
      phase transition in breast cancer cells, which was associated with activation of
      AKT, suppression of FOXO1 transactivity, downregulation of cyclin-dependent
      kinase inhibitors p21Cip1 and p27Kip1 and upregulation of the cell cycle
      regulator cyclin D1. CONCLUSIONS: Taken together, these findings provide new
      evidence that AGK plays an important role in promoting proliferation and
      tumorigenesis in human breast cancer and may serve as a novel prognostic
      biomarker and therapeutic target in this disease.

PMID- 24886248
TI  - Antiviral drug valacyclovir treatment combined with a clean feeding system
      enhances the suppression of salivary gland hypertrophy in laboratory colonies of
      Glossina pallidipes.
AB  - BACKGROUND: Hytrosaviridae cause salivary gland hypertrophy (SGH) syndrome in
      some infected tsetse flies (Diptera: Glossinidae). Infected male and female G.
      pallidipes with SGH have a reduced fecundity and fertility. Due to the
      deleterious impact of the virus on G. pallidipes colonies, adding the antiviral
      drug valacyclovir to the blood diet and changing the feeding regime to a clean
      feeding system (each fly receives for each feeding a fresh clean blood meal) have
      been investigated to develop virus management strategies. Although both
      approaches used alone successfully reduced the virus load and the SGH prevalence
      in small experimental groups, considerable time was needed to obtain the desired
      SGH reduction and both systems were only demonstrated with colonies that had a
      low initial virus prevalence (SGH <= 10%). As problems with SGH are often only
      recognized once the incidence is already high, it was necessary to demonstrate
      that this combination would also work for high prevalence colonies. FINDINGS:
      Combining both methods at colony level successfully suppressed the SGH in G.
      pallidipes colonies that had a high initial virus prevalence (average SGH of
      24%). Six months after starting the combined treatment SGH symptoms were
      eliminated from the treated colony, in contrast to 28 months required to obtain
      the same results using clean feeding alone and 21 months using antiviral drug
      alone. CONCLUSIONS: Combining valacyclovir treatment with the clean feeding
      system provides faster control of SGH in tsetse than either method alone and is
      effective even when the initial SGH prevalence is high.

PMID- 24886249
TI  - A case of Penicillium marneffei infection involving the main tracheal structure.
AB  - BACKGROUND: Penicillium marneffei is the only dimorphic member of the genus and
      is an emerging pathogenic fungus that can cause fatal systemic mycosis.
      Penicillium marneffei disseminates hematogenously to other locations. Penicillium
      marneffei infection most commonly involves the skin, lungs, and
      reticuloendothelial system, including the bone, bone marrow, joints, lymph nodes,
      pericardium, liver, and spleen. Involvement of the mesenteric and central nervous
      systems has also been reported. Infection involving the trachea has not been
      previously reported. CASE PRESENTATION: We herein report a previously healthy 28
      year-old male farmer from Guangxi Province without HIV who became infected with
      P. marneffei. The infection primarily affected the trachea, resulting in
      structural damage to the cartilage, tracheal stenosis, and tracheal absence. The
      infection also involved the lungs and lymph nodes. After antifungal treatment and
      surgery, his symptoms, signs, and lung imaging findings showed significant
      improvement. This is the first such case report. CONCLUSION: Penicillium
      marneffei infection in normal hosts is characterized by an insidious onset,
      various clinical manifestations, and common misdiagnosis, leading to high
      mortality rates. Penicillium marneffei hematogenously disseminates throughout the
      whole body. This is the first reported case of P. marneffei infection involving
      the main trachea with subsequent structural damage to the tracheal cartilage,
      severe tracheostenosis, and tracheal absence.

PMID- 24886250
TI  - KRLMM: an adaptive genotype calling method for common and low frequency variants.
AB  - BACKGROUND: SNP genotyping microarrays have revolutionized the study of complex
      disease. The current range of commercially available genotyping products contain
      extensive catalogues of low frequency and rare variants. Existing SNP calling
      algorithms have difficulty dealing with these low frequency variants, as the
      underlying models rely on each genotype having a reasonable number of
      observations to ensure accurate clustering. RESULTS: Here we develop KRLMM, a new
      method for converting raw intensities into genotype calls that aims to overcome
      this issue. Our method is unique in that it applies careful between sample
      normalization and allows a variable number of clusters k (1, 2 or 3) for each
      SNP, where k is predicted using the available data. We compare our method to four
      genotyping algorithms (GenCall, GenoSNP, Illuminus and OptiCall) on several
      Illumina data sets that include samples from the HapMap project where the true
      genotypes are known in advance. All methods were found to have high overall
      accuracy (> 98%), with KRLMM consistently amongst the best. At low minor allele
      frequency, the KRLMM, OptiCall and GenoSNP algorithms were observed to be
      consistently more accurate than GenCall and Illuminus on our test data.
      CONCLUSIONS: Methods that tailor their approach to calling low frequency variants
      by either varying the number of clusters (KRLMM) or using information from other
      SNPs (OptiCall and GenoSNP) offer improved accuracy over methods that do not
      (GenCall and Illuminus). The KRLMM algorithm is implemented in the open-source
      crlmm package distributed via the Bioconductor project
      (http://www.bioconductor.org).

PMID- 24886251
TI  - An intron polymorphism of the fibronectin gene is associated with end-stage knee
      osteoarthritis in a Han Chinese population: two independent case-control studies.
AB  - BACKGROUND: Knee osteoarthritis (OA) is a complex disease involving both
      biomechanical and metabolic factors that alter the tissue homeostasis of
      articular cartilage and subchondral bone. The catabolic activities of
      extracellular matrix degradation products, especially fibronectin (FN), have been
      implicated in mediating cartilage degradation. Chondrocytes express several
      members of the integrin family which can serve as receptors for FN including
      integrins alpha5beta1, alphavbeta3, and alphavbeta5. The purpose of this study
      was to determine whether polymorphisms in the FN (FN-1) and integrin genes are
      markers of susceptibility to, or severity of, knee OA in a Han Chinese
      population. METHODS: Two independent case-control studies were conducted on 928
      patients with knee OA and 693 healthy controls. Ten single nucleotide
      polymorphisms (SNPs) of FN-1 and the integrin alphaV gene (ITGAV) were detected
      using the ABI 7500 real-time PCR system. RESULTS: The AT heterozygote in FN-1
      (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR
      = 1.44; 95% CI = 1.16-1.80) in both stages of the study. FN-1 rs6725958C/A and
      ITGAV rs10174098A/G SNPs were only associated with knee OA when both study groups
      were combined. Stratifying the participants by Kellgren-Lawrence (KL) score
      identified significant differences in the FN-1 rs6725958C/A and rs940739 A/T
      genotypes between patients with grade 4 OA and controls. Haplotype analyses
      revealed that TGA and TAA were associated with a higher risk of OA, and that TAG
      conferred a lower risk of knee OA in the combined population. CONCLUSIONS: Our
      study suggests that the FN-1 rs940739A/T polymorphism may be an important risk
      factor of genetic susceptibility to knee OA in the Han Chinese population.

PMID- 24886253
TI  - An adaptive Kalman filter approach for cardiorespiratory signal extraction and
      fusion of non-contacting sensors.
AB  - BACKGROUND: Extracting cardiorespiratory signals from non-invasive and non
      contacting sensor arrangements, i.e. magnetic induction sensors, is a challenging
      task. The respiratory and cardiac signals are mixed on top of a large and time
      varying offset and are likely to be disturbed by measurement noise. Basic
      filtering techniques fail to extract relevant information for monitoring
      purposes. METHODS: We present a real-time filtering system based on an adaptive
      Kalman filter approach that separates signal offsets, respiratory and heart
      signals from three different sensor channels. It continuously estimates
      respiration and heart rates, which are fed back into the system model to enhance
      performance. Sensor and system noise covariance matrices are automatically
      adapted to the aimed application, thus improving the signal separation
      capabilities. We apply the filtering to two different subjects with different
      heart rates and sensor properties and compare the results to the non-adaptive
      version of the same Kalman filter. Also, the performance, depending on the
      initialization of the filters, is analyzed using three different configurations
      ranging from best to worst case. RESULTS: Extracted data are compared with
      reference heart rates derived from a standard pulse-photoplethysmographic sensor
      and respiration rates from a flowmeter. In the worst case for one of the subjects
      the adaptive filter obtains mean errors (standard deviations) of -0.2 min(-1)
      (0.3 min(-1)) and -0.7 bpm (1.7 bpm) (compared to -0.2 min(-1) (0.4 min(-1)) and
      42.0 bpm (6.1 bpm) for the non-adaptive filter) for respiration and heart rate,
      respectively. In bad conditions the heart rate is only correctly measurable when
      the Kalman matrices are adapted to the target sensor signals. Also, the reduced
      mean error between the extracted offset and the raw sensor signal shows that
      adapting the Kalman filter continuously improves the ability to separate the
      desired signals from the raw sensor data. The average total computational time
      needed for the Kalman filters is under 25% of the total signal length rendering
      it possible to perform the filtering in real-time. CONCLUSIONS: It is possible to
      measure in real-time heart and breathing rates using an adaptive Kalman filter
      approach. Adapting the Kalman filter matrices improves the estimation results and
      makes the filter universally deployable when measuring cardiorespiratory signals.

PMID- 24886252
TI  - Bisphenol A and the female reproductive tract: an overview of recent laboratory
      evidence and epidemiological studies.
AB  - Bisphenol A (BPA) is a high production volume monomer used for making a wide
      variety of polycarbonate plastics and resins. A large body of evidence links BPA
      to endocrine disruption in laboratory animals, and a growing number of
      epidemiological studies support a link with health disorders in humans. The aim
      of this review is to summarize the recent experimental studies describing the
      effects and mechanisms of BPA on the female genital tract and to compare them to
      the current knowledge regarding the impact of BPA impact on female reproductive
      health. In particular, BPA has been correlated with alterations in hypothalamic
      pituitary hormonal production, reduced oocyte quality due to perinatal and
      adulthood exposure, defective uterine receptivity and the pathogenesis of
      polycystic ovary syndrome. Researchers have reported conflicting results
      regarding the effect of BPA on premature puberty and endometriosis development.
      Experimental studies suggest that BPA's mechanism of action is related to life
      stage and that its effect on the female reproductive system may involve agonism
      with estrogen nuclear receptors as well as other mechanisms (steroid biosynthesis
      inhibition). Notwithstanding uncertainties and knowledge gaps, the available
      evidence should be seen as a sufficient grounds to take precautionary actions
      against excess exposure to BPA. 

PMID- 24886254
TI  - Anti-mullerian hormone is expressed by endometriosis tissues and induces cell
      cycle arrest and apoptosis in endometriosis cells.
AB  - BACKGROUND: The anti-mullerian hormone (AMH) is a member of the transforming
      growth factor beta (TGF-beta) superfamily, which is responsible of the regression
      of the mullerian duct. AMH is expressed in the normal endometrium, where, acting
      in a paracrine fashion, negatively regulates cellular viability. Our objective
      was to evaluate the in vitro effects of the treatment with AMH of endometriosic
      cells. METHODS: AMH expression in human endometriosis glands was evaluated by
      immunohistochemistry. RT-PCR has been used to quantify the expression levels of
      AMH and AMH RII isoforms, as well as of cytochrome P450 in both endometriosis
      epithelial and stromal cells Effects of AMH and AMH-cleaved treatment in
      endometriosis cells were evaluated by flow-cytometry analysis. Finally, it has
      been evaluated the effect of plasmin-digested AMH on cytochrome P450 activity.
      RESULTS: AMH and AMH RII isoforms, as well as cytochrome P450, were expressed in
      both endometriosis epithelial and stromal cells. Treatment of endometriosis
      stromal and epithelial cell growth with AMH was able to induce a decrease in the
      percentage of cells in S phase and increase percentage of cells in G1 and G2
      phase; coherently, decreased cell viability and increased percentage of cells
      death fraction was observed. The plasmin-digested AMH was able to suppress most
      of the cytochrome P450 activity, causing an increase of pre-G1 phase and of
      apoptosis induction treating with plasmin-digested AMH in both cell lines, most
      marked in the epithelial cells. CONCLUSIONS: The data produced suggest a possible
      use of AMH as therapeutic agents in endometriosis.

PMID- 24886255
TI  - Tubal ectopic pregnancy two years after laparoscopic supracervical hysterectomy.
AB  - BACKGROUND: Ectopic pregnancy after hysterectomy is a very rare condition, but it
      must be kept in mind in women with history of hysterectomy who present with
      abdominal pain and ecographic adnexal heterogeneous images. Since first described
      by Wendeler in 1895, at least 67 ectopic pregnancies (tubal, ovarian and
      abdominal) have been described in patients subjected to prior hysterectomy. CASE
      PRESENTATION: We describe the case of a 41-year-old white caucasian woman
      admitted to the emergency room due to abdominal pain for two days. The
      ultrasounds scan and the quantification of beta-HCG led to the diagnosis of tubal
      ectopic pregnancy, although she had been hysterectomized two years before. An
      emergency laparoscopy was performed for salpingectomy. The pathology report
      indicated trophoblastic tubal implantation and hematosalpinx. CONCLUSIONS:
      Ectopic pregnancy is one of the conditions to be considered in the differential
      diagnosis of abdominal pain in women of child bearing potential, and the absence
      of the uterus does not rule out its diagnosis.

PMID- 24886256
TI  - Physiological assessment of Olympic windsurfers.
AB  - Olympic boardsailing is a very demanding endurance sport activity. The main
      reason for this phenomenon is ascribable to the fact that elite windsurfers use
      pumping for propulsion during sailing. Pumping is a manoeuvre in which the
      athlete pulls the sail rhythmically so that it acts as a wing, thus providing the
      board with additional forward motion especially in light and moderate wind
      conditions. It has been demonstrated, by using portable metabolimeters, that
      Olympic boardsailing (Mistral board and the current Olympic board the Neil Pryde
      RS:X) entails high energy and cardiorespiratory requirements. In elite Olympic
      board-sailors, by measuring energy costs and cardiorespiratory responses, it was
      found that (in wind velocity conditions ranging between 4 and 15 m s(-1))
      pumping, compared to non-pumping sailing, induced a significant increase in
      oxygen uptake (VO2) and heart rate (HR) demands (from 19.2 to 48.4 ml min(-1) kg(
      1) and from 110 to 165 beats min(-1), respectively). In general, across studies
      the aerobic demand, recorded on various windsurf boards (expressed as% VO2max),
      was greater than 75%, whilst HR values were greater than 85% of HRmax during
      actual racing conditions. In conclusion, Olympic class windsurfing can be
      considered as a high-intensity endurance type of sport that is comparable to
      other aerobic sporting activities such as rowing. Sail pumping is the crucial
      factor determining this high intensity of aerobic demand. Moreover, the fact that
      a typical regatta includes many races over several days implies that particular
      attention must be paid to the training strategy and the nutritional requirement
      of this discipline.

PMID- 24886257
TI  - Age estimates for an adaptive lake fish radiation, its mitochondrial
      introgression, and an unexpected sister group: Sailfin silversides of the Malili
      Lakes system in Sulawesi.
AB  - BACKGROUND: The Malili Lakes system in central Sulawesi (Indonesia) is a hotspot
      of freshwater biodiversity in the Wallacea, characterized by endemic species
      flocks like the sailfin silversides (Teleostei: Atherinomorpha: Telmatherinidae)
      radiation. Phylogenetic reconstructions of these freshwater fishes have
      previously revealed two Lake Matano Telmatherina lineages (sharpfins and
      roundfins) forming an ancient monophyletic group, which is however masked by
      introgressive hybridization of sharpfins with riverine populations. The present
      study uses mitochondrial data, newly included taxa, and different external
      calibration points, to estimate the age of speciation and hybridization
      processes, and to test for phylogeographic relationships between Kalyptatherina
      from ancient islands off New Guinea, Marosatherina from SW Sulawesi, and the
      Malili Lakes flock. RESULTS: Contrary to previous expectations, Kalyptatherina is
      the closest relative to the Malili Lakes Telmatherinidae, and Marosatherina is
      the sister to this clade. Palaeogeographic reconstructions of Sulawesi suggest
      that the closer relationship of the Malili Lakes radiation to Kalyptatherina
      might be explained by a 'terrane-rafting' scenario, while proto-Marosatherina
      might have colonized Sulawesi by marine dispersal. The most plausible analysis
      conducted here implies an age of c. 1.9 My for the onset of divergence between
      the two major clades endemic to Lake Matano. Diversification within both lineages
      is apparently considerably more recent (c. 1.0 My); stream haplotypes present in
      the sharpfins are of even more recent origin (c. 0.4 My). CONCLUSIONS: Sulawesi's
      Telmatherinidae have most likely originated in the Sahul Shelf area, have
      possibly reached the island by both, marine dispersal and island/terrane-rafting,
      and have colonized the Malili Lakes system from rivers. Estimates for the split
      between the epibenthic sharpfins and the predominantly pelagic to benthopelagic
      roundfins in Lake Matano widely coincide with geological age estimates of this
      rift lake. Diversification within both clades clearly predates hybridization
      events with stream populations. For Lake Matano, these results support a scenario
      of initial benthic-pelagic divergence after colonization of the lake by riverine
      populations, followed by rapid radiation within both clades within the last 1 My.
      Secondary hybridization of stream populations with the sharpfins occurred more
      recently, and has thus most likely not contributed to the initial divergence of
      this benthic species flock.

PMID- 24886258
TI  - Migraine among medical students in Kuwait University.
AB  - BACKGROUND: Medical students routinely have triggers, notably stress and
      irregular sleep, which are typically associated with migraine. We hypothesized
      that they may be at higher risk to manifest migraine. We aimed to determine the
      prevalence of migraine among medical students in Kuwait University. METHODS: This
      is cross-sectional, questionnaire-based study. Participants who had two or more
      headaches in the last 3 months were subjected to two preliminary questions and
      participants with at least one positive response were asked to perform the
      validated Identification of Migraine (ID MigraineTM) test. Frequency of headache
      per month and its severity were also reported. RESULTS: Migraine headache was
      suggested in 27.9% subjects based on ID-MigraineTM. Migraine prevalence (35.5%
      and 44%, versus 31.1%, 25%, 21.1%, 14.8%, 26.5%, p < 0.000), frequency (5.55 +
      1.34 and 7.23 + 1.27, versus 3.77 +/- 0.99, 2.88 +/- 0.85, 3.07 +/- 0.96, 2.75 +/
      0.75, 4.06 +/- 1.66, p < 0.000); and severity of headache (59.1% and 68.2%,
      versus 28.3%,8.3%, 6.7%,16.7%, p < 0.000; were significantly increased among
      students in the last 2 years compared to first five years of their study. Stress
      43 (24.9%), irregular sleep 36 (20.8%), and substantial reading tasks 32 (18.5%),
      were the most common triggering factors cited by the students. CONCLUSION: The
      prevalence of migraine is higher among medical students in Kuwait University
      compared to other published studies. The migraine prevalence, frequency and
      headache severity, all increased in the final two years of education.

PMID- 24886260
TI  - Inhalation of honey reduces airway inflammation and histopathological changes in
      a rabbit model of ovalbumin-induced chronic asthma.
AB  - BACKGROUND: Honey is widely used in folk medicine to treat cough, fever, and
      inflammation. In this study, the effect of aerosolised honey on airway tissues in
      a rabbit model of ovalbumin (OVA)-induced asthma was investigated. The ability of
      honey to act either as a rescuing agent in alleviating asthma-related symptoms or
      as a preventive agent to preclude the occurrence of asthma was also assessed.
      METHODS: Forty New Zealand white rabbits were sensitized twice with mixture of
      OVA and aluminium hydroxide on days 1 and 14. Honey treatments were given from
      day 23 to day 25 at two different doses (25% (v/v) and 50% (v/v) of honey diluted
      in sterile phosphate buffer saline. In the aerosolised honey as a rescue agent
      group, animals were euthanized on day 28; for the preventive group, animals were
      further exposed to aerosolised OVA for 3 days starting from day 28 and euthanized
      on day 31. The effects of honey on inflammatory cell response, airway
      inflammation, and goblet cell hyperplasia were assessed for each animal. RESULTS:
      Histopathological analyses revealed that aerosolised honey resulted in structural
      changes of the epithelium, mucosa, and submucosal regions of the airway that
      caused by the induction with OVA. Treatment with aerosolised honey has reduced
      the number of airway inflammatory cells present in bronchoalveolar lavage fluid
      and inhibited the goblet cell hyperplasia. CONCLUSION: In this study, aerosolised
      honey was used to effectively treat and manage asthma in rabbits, and it could
      prove to be a promising treatment for asthma in humans. Future studies with a
      larger sample size and studies at the gene expression level are needed to better
      understand the mechanisms by which aerosolised honey reduces asthma symptoms.

PMID- 24886259
TI  - Polysaccharides from Liriopes Radix ameliorate streptozotocin-induced type I
      diabetic nephropathy via regulating NF-kappaB and p38 MAPK signaling pathways.
AB  - BACKGROUND: The polysaccharides from Liriopes Radix (PSLR) has been indicated to
      ameliorate insulin signaling transduction and glucose metabolism. We aimed to
      investigate whether PSLR exerts an ameliorative effect on renal damage in
      diabetes induced by streptozotocin. METHODS: Diabetes was induced with STZ (60
      mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats
      in the treatment group were orally dosed with PSLR (200 and 300 mg/kg/day for 8
      weeks. The normal rats were chosen as nondiabetic control group. Changes in renal
      function-related parameters in plasma and urine were analyzed at the end of the
      study. Kidneys were isolated for pathology histology, immunohistochemistry, and
      Western blot analyses. RESULTS: Diabetic rats exhibited renal dysfunction, as
      evidenced by reduced creatinine clearance, blood urea nitrogen and proteinuria,
      along with marked elevation in the ratio of kidney weight to body weight. All of
      these abnormalities were significantly reversed by PSLR. The histological
      examinations revealed amelioration of diabetes-induced glomerular pathological
      changes following treatment with PSLR. The less protein expressions of renal
      nephrin and podocin in diabetic rats were increased following treatment with
      PSLR. PSLR reduced the accumulation of ED-1-expressing macrophages in renal
      tissue of diabetic rats. PSLR almost completely abolished T cells infiltration
      and attenuated the expression of proinflammatory cytokines. PSLR treatments not
      only reduced the degradation of inhibitory kappa B kinase, but also downregulated
      the protein expression of nuclear factor kappa B (NF-kappaB) and p38 mitogen
      activated protein kinase (MAPK) in diabetic kidney. CONCLUSIONS: The results
      suggest that the renal protective effects of PSLR occur through improved glycemic
      control and renal structural changes, which are involved in the inhibition of NF
      kappaB and p-38 MAPK mediated inflammation.

PMID- 24886261
TI  - Polycystic liver disease: an overview of pathogenesis, clinical manifestations
      and management.
AB  - Polycystic liver disease (PLD) is the result of embryonic ductal plate
      malformation of the intrahepatic biliary tree. The phenotype consists of numerous
      cysts spread throughout the liver parenchyma. Cystic bile duct malformations
      originating from the peripheral biliary tree are called Von Meyenburg complexes
      (VMC). In these patients embryonic remnants develop into small hepatic cysts and
      usually remain silent during life. Symptomatic PLD occurs mainly in the context
      of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic
      kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have
      massively enlarged livers which cause a spectrum of clinical features and
      complications. Major complaints include abdominal pain, abdominal distension and
      atypical symptoms because of voluminous cysts resulting in compression of
      adjacent tissue or failure of the affected organ. Renal failure due to polycystic
      kidneys and non-renal extra-hepatic features are common in ADPKD in contrast to
      VMC and PCLD. In general, liver function remains prolonged preserved in PLD.
      Ultrasonography is the first instrument to assess liver phenotype. Indeed, PCLD
      and ADPKD diagnostic criteria rely on detection of hepatorenal cystogenesis, and
      secondly a positive family history compatible with an autosomal dominant
      inheritance pattern. Ambiguous imaging or screening may be assisted by genetic
      counseling and molecular diagnostics. Screening mutations of the genes causing
      PCLD (PRKCSH and SEC63) or ADPKD (PKD1 and PKD2) confirm the clinical diagnosis.
      Genetic studies showed that accumulation of somatic hits in cyst epithelium
      determine the rate-limiting step for cyst formation. Management of adult PLD is
      based on liver phenotype, severity of clinical features and quality of life.
      Conservative treatment is recommended for the majority of PLD patients. The
      primary aim is to halt cyst growth to allow abdominal decompression and
      ameliorate symptoms. Invasive procedures are required in a selective patient
      group with advanced PCLD, ADPKD or liver failure. Pharmacological therapy by
      somatostatin analogues lead to beneficial outcome of PLD in terms of symptom
      relief and liver volume reduction. 

PMID- 24886262
TI  - High yield production of pigeon circovirus capsid protein in the E. coli by
      evaluating the key parameters needed for protein expression.
AB  - BACKGROUND: Pigeon circovirus (PiCV) is considered to be a viral agent central to
      the development of young pigeon disease syndrome (YPDS). The Cap protein, a
      structural protein encoded by the cap (or C1) gene of PiCV, has been shown to be
      responsible for not only capsid assembly, but also has been used as antigen for
      detecting antibody when the host is infected with PiCV. The antigenic
      characteristics of the Cap protein potentially may allow the development of a
      detection kit that could be applied to control PiCV infection. However, poor
      expression and poor protein solubility have hampered the production of
      recombinant Cap protein in the bacteria. This study was undertaken to develop the
      optimal expression of recombinant full-length Cap protein of PiCV using an E.
      coli expression system. RESULTS: The PiCV cap gene was cloned and fused with
      different fusion partners including a His-tag, a GST-tag (glutathioine-S
      transferase tag) and a Trx-His-tag (thioredoxin-His tag). The resulting
      constructs were then expressed after transformation into a number of different E.
      coli strains; these then had their protein expression evaluated. The expression
      of the recombinant Cap protein in E. coli was significantly increased when Cap
      protein was fused with either a GST-tag or a Trx-His tag rather than a His-tag.
      After various rare amino acid codons presented in the Cap protein were optimized
      to give the sequence rCapopt, the expression level of the GST-rCapopt in E. coli
      BL21(DE3) was further increased to a significant degree. The highest protein
      expression level of GST-rCapopt obtained was 394.27 +/- 26.1 mg/L per liter using
      the E. coli strain BL21(DE3)-pLysS. Moreover, approximately 74.5% of the
      expressed GST-rCapopt was in soluble form, which is higher than the soluble Trx
      His-rCapopt expressed using the BL21(DE3)-pLysS strain. After purification using
      a GST affinity column combined with ion-exchange chromatography, the purified
      recombinant GST-rCapopt protein was found to have good antigenic activity when
      tested against PiCV-infected pigeon sera. CONCLUSIONS: These findings shows that
      the E. coli-expressed full-length PiCV Cap protein has great potential in terms
      of large-scaled production and this should allow in the future the development of
      a serodiagnostic kit that is able to clinically detect PiCV infection in pigeons.

PMID- 24886263
TI  - Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and
      induces necrosis in alveolar macrophages.
AB  - BACKGROUND: Phospholipases C (PLCs) are virulence factors found in several
      bacteria. In Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on
      macrophages, but the mechanisms involved in PLC-induced cell death are not fully
      understood. It has been reported that induction of cell necrosis by virulent Mtb
      is coordinated by subversion of PGE2, an essential factor in cell membrane
      protection. RESULTS: Using two Mtb clinical isolates carrying genetic variations
      in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes,
      is more resistant to alveolar macrophage microbicidal activity than the isolate
      97-1200, which has all PLC genes deleted. The isolate 97-1505 also induced higher
      rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression
      and PGE2 production. To address the direct effect of mycobacterial PLC on cell
      necrosis and PGE2 inhibition, both isolates were treated with PLC inhibitors
      prior to macrophage infection. Interestingly, inhibition of PLCs affected the
      ability of the isolate 97-1505 to induce necrosis, leading to cell death rates
      similar to those induced by the isolate 97-1200. Finally, PGE2 production by Mtb
      97-1505-infected macrophages was restored to levels similar to those produced by
      97-1200-infected cells. CONCLUSIONS: Mycobacterium tuberculosis bearing PLCs
      genes induces alveolar macrophage necrosis, which is associated to subversion of
      PGE2 production.

PMID- 24886264
TI  - Ringing Up about Breastfeeding: a randomised controlled trial exploring early
      telephone peer support for breastfeeding (RUBY) - trial protocol.
AB  - BACKGROUND: The risks of not breastfeeding for mother and infant are well
      established, yet in Australia, although most women initiate breastfeeding many
      discontinue breastfeeding altogether and few women exclusively breastfeed to six
      months as recommended by the World Health Organization and Australian health
      authorities. We aim to determine whether proactive telephone peer support during
      the postnatal period increases the proportion of infants who are breastfed at six
      months, replicating a trial previously found to be effective in Canada.
      DESIGN/METHODS: A two arm randomised controlled trial will be conducted,
      recruiting primiparous women who have recently given birth to a live baby, are
      proficient in English and are breastfeeding or intending to breastfeed. Women
      will be recruited in the postnatal wards of three hospitals in Melbourne,
      Australia and will be randomised to peer support or to 'usual' care. All women
      recruited to the trial will receive usual hospital postnatal care and infant
      feeding support. For the intervention group, peers will make two telephone calls
      within the first ten days postpartum, then weekly telephone calls until week
      twelve, with continued contact until six months postpartum. Primary aim: to
      determine whether postnatal telephone peer support increases the proportion of
      infants who are breastfed for at least six months. HYPOTHESIS: that telephone
      peer support in the postnatal period will increase the proportion of infants
      receiving any breast milk at six months by 10% compared with usual care (from 46%
      to 56%).Outcome data will be analysed by intention to treat. A supplementary
      multivariate analysis will be undertaken if there are any baseline differences in
      the characteristics of women in the two groups which might be associated with the
      primary outcomes. DISCUSSION: The costs and health burdens of not breastfeeding
      fall disproportionately and increasingly on disadvantaged groups. We have
      therefore deliberately chosen trial sites which have a high proportion of women
      from disadvantaged backgrounds. This will be the first Australian randomised
      controlled trial to test the effectiveness and cost effectiveness of proactive
      peer telephone support for breastfeeding. TRIAL REGISTRATION: Australian and New
      Zealand Clinical Trials Registry ACTRN12612001024831.

PMID- 24886265
TI  - Longitudinal associations between incident lumbar spine MRI findings and chronic
      low back pain or radicular symptoms: retrospective analysis of data from the
      longitudinal assessment of imaging and disability of the back (LAIDBACK).
AB  - BACKGROUND: There are few longitudinal cohort studies examining associations
      between incident MRI findings and incident spine-related symptom outcomes. Prior
      studies do not discriminate between the two distinct outcomes of low back pain
      (LBP) and radicular symptoms. To address this gap in the literature, we conducted
      a secondary analysis of existing data from the Longitudinal Assessment of Imaging
      and Disability of the Back (LAIDBACK). The purpose of this study was to examine
      the association of incident lumbar MRI findings with two specific spine-related
      symptom outcomes: 1) incident chronic bothersome LBP, and 2) incident radicular
      symptoms such as pain, weakness, or sensation alterations in the lower extremity.
      METHODS: The original LAIDBACK study followed 123 participants without current
      LBP or sciatica, administering standardized MRI assessments of the lumbar spine
      at baseline and at 3-year follow-up, and collecting information on participant
      reported spine-related symptoms and signs every 4 months for 3 years. These
      analyses examined bivariable and multivariable associations between incident MRI
      findings and symptom outcomes (LBP and radicular symptoms) using logistic
      regression. RESULTS: Three-year cumulative incidence of new MRI findings ranged
      between 2 and 8%, depending on the finding. Incident annular fissures were
      associated with incident chronic LBP, after adjustment for prior back pain and
      depression (adjusted odds ratio [OR] 6.6; 95% confidence interval [CI] 1.2-36.9).
      All participants with incident disc extrusions (OR 5.4) and nerve root
      impingement (OR 4.1) reported incident radicular symptoms, although associations
      were not statistically significant. No other incident MRI findings showed large
      magnitude associations with symptoms. CONCLUSIONS: Even when applying more
      specific definitions for spine-related symptom outcomes, few MRI findings showed
      large magnitude associations with symptom outcomes. Although incident annular
      fissures, disc extrusions, and nerve root impingement were associated with
      incident symptom outcomes, the 3-year incidence of these MRI findings was
      extremely low, and did not explain the vast majority of incident symptom cases.

PMID- 24886266
TI  - High proportion of knowlesi malaria in recent malaria cases in Malaysia.
AB  - BACKGROUND: Plasmodium knowlesi is a simian parasite that has been recognized as
      the fifth species causing human malaria. Naturally-acquired P. knowlesi infection
      is widespread among human populations in Southeast Asia. The aim of this
      epidemiological study was to determine the incidence and distribution of malaria
      parasites, with a particular focus on human P. knowlesi infection in Malaysia.
      METHODS: A total of 457 microscopically confirmed, malaria-positive blood samples
      were collected from 22 state and main district hospitals in Malaysia between
      September 2012 and December 2013. Nested PCR assay targeting the 18S rRNA gene
      was used to determine the infecting Plasmodium species. RESULTS: A total of 453
      samples were positive for Plasmodium species by using nested PCR assay.
      Plasmodium knowlesi was identified in 256 (56.5%) samples, followed by 133
      (29.4%) cases of Plasmodium vivax, 49 (10.8%) cases of Plasmodium falciparum, two
      (0.4%) cases of Plasmodium ovale and one (0.2%) case of Plasmodium malariae.
      Twelve mixed infections were detected, including P. knowlesi/P. vivax (n = 10),
      P. knowlesi/P. falciparum (n = 1), and P. falciparum/P. vivax (n = 1). Notably,
      P. knowlesi (Included mixed infections involving P. knowlesi (P. knowlesi/P.
      vivax and P. knowlesi /P. falciparum)) showed the highest proportion in Sabah
      (84/115 cases, prevalence of 73.0%), Sarawak (83/120, 69.2%), Kelantan (42/56,
      75.0%), Pahang (24/25, 96.0%), Johor (7/9, 77.8%), and Terengganu (4/5, 80.0%,).
      In contrast, the rates of P. knowlesi infection in Selangor and Negeri Sembilan
      were found to be 16.2% (18/111 cases) and 50.0% (5/10 cases), respectively.
      Sample of P. knowlesi was not obtained from Kuala Lumpur, Melaka, Perak, Pulau
      Pinang, and Perlis during the study period, while a microscopically-positive
      sample from Kedah was negative by PCR. CONCLUSION: In addition to Sabah and
      Sarawak, which have been known for high prevalence of P. knowlesi infection, the
      findings from this study highlight the widespread distribution of P. knowlesi in
      many Peninsular Malaysia states.

PMID- 24886267
TI  - Building capacity to develop an African teaching platform on health workforce
      development: a collaborative initiative of universities from four sub Saharan
      countries.
AB  - INTRODUCTION: Health systems in many low-income countries remain fragile, and the
      record of human resource planning and management in Ministries of Health very
      uneven. Public health training institutions face the dual challenge of building
      human resources capacity in ministries and health services while alleviating and
      improving their own capacity constraints. This paper reports on an initiative
      aimed at addressing this dual challenge through the development and
      implementation of a joint Masters in Public Health (MPH) programme with a focus
      on health workforce development by four academic institutions from East and
      Southern Africa and the building of a joint teaching platform. METHODS: Data were
      obtained through interviews and group discussions with stakeholders, direct and
      participant observations, and reviews of publications and project documents. Data
      were analysed using thematic analysis. CASE DESCRIPTION: The institutions
      developed and collaboratively implemented a 'Masters Degree programme with a
      focus on health workforce development'. It was geared towards strengthening the
      leadership capacity of Health ministries to develop expertise in health human
      resources (HRH) planning and management, and simultaneously build capacity of
      faculty in curriculum development and innovative educational practices to teach
      health workforce development. The initiative was configured to facilitate sharing
      of experience and resources. DISCUSSION: The implementation of this initiative
      has been complex, straddling multiple and changing contexts, actors and agendas.
      Some of these are common to postgraduate programmes with working learners, while
      others are unique to this particular partnership, such as weak institutional
      capacity to champion and embed new programmes and approaches to teaching.
      CONCLUSIONS: The partnership, despite significant inherent challenges, has
      potential for providing real opportunities for building the field and community
      of practice, and strengthening the staff and organizational capacity of
      participant institutions. Key learning points of the paper are:* the need for
      long-term strategies and engagement;* the need for more investment and attention
      to developing the capacity of academic institutions;* the need to invest
      specifically in educational/teaching expertise for innovative approaches to
      teaching and capacity development more broadly; and* the importance of increasing
      access and support for students who are working adults in public health
      institutions throughout Africa.

PMID- 24886268
TI  - Selective serotonin reuptake inhibitors and endothelial function in women.
AB  - BACKGROUND: Among women worldwide, major depression (MDD) and heart disease rank
      first and second, respectively, in burden of disease. Although selective
      serotonin reuptake inhibitors (SSRIs) are frequently prescribed, possible
      inhibition of nitric oxide (NO) function has caused concerns about their effects
      on protective vascular mechanisms. Our study aimed to determine the effect of
      SSRIs on flow-mediated vascular dilatation (FMD), platelet aggregation, and
      platelet NO production among women. METHODS: Women (n=28) without known
      cardiovascular disease were recruited prior to undergoing SSRI treatment for MDD,
      postpartum depression (PPD), or premenstrual dysphoric disorder (PMDD). Symptoms
      were quantified using the Hamilton Depression/Anxiety and Beck Depression scales.
      FMD, platelet aggregation, and platelet NO production were measured before and
      after 1 month of SSRI (sertraline, fluoxetine, or paroxetine) therapy. RESULTS:
      Depression and anxiety symptoms decreased significantly with SSRI treatment (ps
      <0.01). FMD and platelet aggregation did not differ between pre- and
      posttreatment, although FMD rose to the normal range (>= 8%) in two of three
      women with abnormal FMD prior to SSRI treatment. We observed a 21% decrease
      (p=0.024) in platelet NO production. CONCLUSIONS: SSRI treatment had little
      effect on FMD or platelet aggregation. The health impact of decreased NO
      production is unclear, particularly in this relatively young group of women
      without cardiovascular disease, but should be considered in future studies
      focusing on SSRI safety in patients with cardiovascular disease.

PMID- 24886269
TI  - Identification and functional characterization of bidirectional gene pairs and
      their intergenic regions in maize.
AB  - BACKGROUND: Bidirectional gene pairs exist as a specific form of gene
      organization in microorganisms and mammals as well as in model plant species,
      such as Arabidopsis and rice. Little is known about bidirectional gene pairs in
      maize, which has a large genome and is one of the most important grain crops.
      RESULTS: We conducted a genome-wide search in maize using genome sequencing
      results from the inbred line B73. In total, 1696 bidirectional transcript pairs
      were identified using a modified search model. We functionally characterized the
      promoter activity of the intergenic regions of most of the bidirectional
      transcript pairs that were expressed in embryos using a maize embryo transient
      expression system. A comparative study of bidirectional gene pairs performed for
      three monocot (Zea mays, Sorghum bicolor and Oryza sativa) and two dicot
      (Arabidopsis thaliana and Glycine max) plant genomes showed that bidirectional
      gene pairs were abundant in the five plant species. Orthologous bidirectional
      gene pairs were clearly distinguishable between the monocot and dicot species
      although the total numbers of orthologous bidirectional genes were similar.
      Analysis of the gene pairs using the Blast2GO software suite showed that the
      molecular functions (MF), cellular components (CC), and biological processes (BP)
      associated with the bidirectional transcripts were similar among the five plant
      species. CONCLUSIONS: The evolutionary analysis of the function and structure of
      orthologous bidirectional gene pairs in various plant species revealed a
      potential pathway of their origin, which may be required for the evolution of a
      new species.

PMID- 24886270
TI  - Low vision due to cerebral visual impairment: differentiating between acquired
      and genetic causes.
AB  - BACKGROUND: To gain more insight into genetic causes of cerebral visual
      impairment (CVI) in children and to compare ophthalmological findings between
      genetic and acquired forms of CVI. METHODS: The clinical data of 309 individuals
      (mainly children) with CVI, and a visual acuity <= 0.3 were analyzed for etiology
      and ocular variables. A differentiation was made between acquired and genetic
      causes. However, in persons with West syndrome or hydrocephalus, it might be
      impossible to unravel whether CVI is caused by the seizure disorder or increased
      intracranial pressure or by the underlying disorder (that in itself can be
      acquired or genetic). In two subgroups, individuals with 'purely' acquired CVI
      and with 'purely' genetic CVI, the ocular variables (such as strabismus, pale
      optic disc and visual field defects) were compared. RESULTS: It was possible to
      identify a putative cause for CVI in 60% (184/309) of the cohort. In the
      remaining 40% the etiology could not be determined. A 'purely' acquired cause was
      identified in 80 of the patients (26%). West syndrome and/or hydrocephalus was
      identified in 21 patients (7%), and in 17 patients (6%) both an acquired cause
      and West and/or hydrocephalus was present. In 66 patients (21%) a genetic
      diagnosis was obtained, of which 38 (12%) had other possible risk factor
      (acquired, preterm birth, West syndrome or hydrocephalus), making differentiation
      between acquired and genetic not possible. In the remaining 28 patients (9%) a
      'purely' genetic cause was identified.CVI was identified for the first time in
      several genetic syndromes, such as ATR-X, Mowat-Wilson, and Pitt Hopkins
      syndrome. In the subgroup with 'purely' acquired causes (N = 80) strabismus (88%
      versus 64%), pale optic discs (65% versus 27%) and visual field defects (72%
      versus 30%) could be observed more frequent than in the subgroup with 'purely'
      genetic disorders (N = 28). CONCLUSIONS: We conclude that CVI can be part of a
      genetic syndrome and that abnormal ocular findings are present more frequently in
      acquired forms of CVI.

PMID- 24886271
TI  - Transcriptomic changes during regeneration of the central nervous system in an
      echinoderm.
AB  - BACKGROUND: Echinoderms are emerging as important models in regenerative biology.
      Significant amount of data are available on cellular mechanisms of post-traumatic
      repair in these animals, whereas studies of gene expression are rare. In this
      study, we employ high-throughput sequencing to analyze the transcriptome of the
      normal and regenerating radial nerve cord (a homolog of the chordate neural
      tube), in the sea cucumber Holothuria glaberrima. RESULTS: Our de novo assembly
      yielded 70,173 contigs, of which 24,324 showed significant similarity to known
      protein-coding sequences. Expression profiling revealed large-scale changes in
      gene expression (4,023 and 3,257 up-regulated and down-regulated transcripts,
      respectively) associated with regeneration. Functional analysis of sets of
      differentially expressed genes suggested that among the most extensively over
      represented pathways were those involved in the extracellular matrix (ECM)
      remodeling and ECM-cell interactions, indicating a key role of the ECM in
      regeneration. We also searched the sea cucumber transcriptome for homologs of
      factors known to be involved in acquisition and/or control of pluripotency. We
      identified eleven genes that were expressed both in the normal and regenerating
      tissues. Of these, only Myc was present at significantly higher levels in
      regeneration, whereas the expression of Bmi-1 was significantly reduced. We also
      sought to get insight into which transcription factors may operate at the top of
      the regulatory hierarchy to control gene expression in regeneration. Our analysis
      yielded eleven putative transcription factors, which constitute good candidates
      for further functional studies. The identified candidate transcription factors
      included not only known regeneration-related genes, but also factors not
      previously implicated as regulators of post-traumatic tissue regrowth. Functional
      annotation also suggested that one of the possible adaptations contributing to
      fast and efficient neural regeneration in echinoderms may be related to
      suppression of excitotoxicity. CONCLUSIONS: Our transcriptomic analysis
      corroborates existing data on cellular mechanisms implicated in regeneration in
      sea cucumbers. More importantly, however, it also illuminates new aspects of
      echinoderm regeneration, which have been scarcely studied or overlooked
      altogether. The most significant outcome of the present work is that it lays out
      a roadmap for future studies of regulatory mechanisms by providing a list of key
      candidate genes for functional analysis.

PMID- 24886273
TI  - Evaluation of a multi-pronged intervention to improve access to safe abortion
      care in two districts in Jharkhand.
AB  - BACKGROUND: Despite the adoption of the Medical Termination of Pregnancy Act in
      1972, access to safe abortion services remains limited in India. Awareness of the
      legality of abortion also remains low, leading many women to seek services
      outside the health system. Medical abortion (MA) is an option that has the
      potential to expand access to safe abortion services. A multi-pronged
      intervention covering a population of 161,000 in 253 villages in the Silli and
      Khunti blocks of Jharkhand was conducted between 2007 and 2009, seeking to
      improve medical abortion services and create awareness at the community level by
      providing information through community intermediaries and creating an enabling
      environment through a behavior change communication campaign. The study evaluates
      the changes in knowledge about abortion-related issues, changes in abortion care
      seeking, and service utilization as a result of this intervention. METHODS: A
      baseline cross-sectional survey was conducted pre-intervention (n = 1,253)
      followed by an endline survey (n = 1,290) one year after the completion of the
      intervention phase. In addition, monitoring data from intervention facilities was
      collected monthly over the study period. RESULTS: Nearly 85% of respondents
      reported being exposed to safe abortion messaging as a result of the
      intervention. Awareness of the legality of abortion increased significantly from
      19.7% to 57.6% for women, as did awareness of the specific conditions for which
      abortion is allowed. Results were similar for men. There was also a significant
      increase in the proportion of men and women who knew of a legal and safe provider
      and place from where abortion services could be obtained. Multivariate analysis
      showed positive associations between exposure to any component of the
      intervention and increased knowledge about legality and gestational age limits,
      however only interpersonal communication was associated with a significant
      increase in knowledge of where to obtain safe services (OR 4.8, SE 0.67).
      Utilization of safe abortion services, and in particular MA, increased at all
      intervention sites over the duration of the intervention with a shift towards
      women seeking care earlier in pregnancy. CONCLUSION: The evaluation demonstrates
      the success of the intervention and its potential for replication in similar
      contexts within India.

PMID- 24886272
TI  - Spironolactone to prevent cardiovascular events in early-stage chronic kidney
      disease (STOP-CKD): study protocol for a randomized controlled pilot trial.
AB  - BACKGROUND: Chronic kidney disease is associated with increased arterial
      stiffness even in the early stages and this is thought to be a key mediator in
      the pathophysiology of the increased cardiovascular risk associated with this
      condition. The use of low-dose spironolactone has previously been shown to
      improve arterial stiffness and reduce left ventricular mass safely in early-stage
      chronic kidney disease in the context of careful monitoring at a university
      hospital. However, the majority of patients with chronic kidney disease are
      managed by their general practitioners in the community. It is not known whether
      similar beneficial effects can be achieved safely using spironolactone in the
      primary care setting. The aim of this study is to determine whether low-dose
      spironolactone can safely lower arterial stiffness in patients with stage 3
      chronic kidney disease in the primary care setting. METHODS/DESIGN: STOP-CKD is a
      multicentre, prospective, randomized, double-blind, placebo-controlled pilot
      trial of 240 adult patients with stage 3 chronic kidney disease recruited from up
      to 20 general practices in South Birmingham, England. Participants will be
      randomly allocated using a secured web-based computer randomization system to
      receive either spironolactone 25 mg once daily or a matching inactive placebo for
      40 weeks, followed by a wash-out period of 6 weeks. Investigators, outcome
      assessors, data analysts and participants will all be blinded to the treatment
      allocation. The primary endpoint is improved arterial stiffness, as measured by
      carotid-femoral pulse wave velocity between baseline and 40 weeks. The secondary
      endpoints are incidence of hyperkalaemia, change in estimated glomerular
      filtration rate, change in urine albumin:creatinine ratio, change in brachial
      blood pressure, change in pulse waveform characteristics and overall tolerability
      of spironolactone. An additional quality control study, aiming to compare the
      laboratory serum potassium results of samples processed via two methods
      (utilizing routine transport or centrifugation on site before rapid transport to
      the laboratory) for 100 participants and a qualitative research study exploring
      patients' and general practitioners' attitudes to research and the use of
      spironolactone in chronic kidney disease in the community setting will be
      embedded in this pilot study. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN80658312.

PMID- 24886274
TI  - Outbreaks of Mycobacterium tuberculosis MDR strains differentially induce
      neutrophil respiratory burst involving lipid rafts, p38 MAPK and Syk.
AB  - BACKGROUND: Neutrophils (PMN) are the first cells to infiltrate the lung after
      infection, and they play a significant protective role in the elimination of
      pathogen, by releasing preformed oxidants and proteolytic enzymes from granules
      and generating ROS, thus limiting inflammation by succumbing to apoptosis. In a
      previous study, we found marked differences in ROS-induced apoptosis between two
      Mycobacterium tuberculosis (Mtb) strains, M and Ra, representative of widespread
      Mtb families in South America, i.e. Haarlem and Latin-American Mediterranean
      (LAM), being strain M able to generate further drug resistance and to disseminate
      aggressively. METHODS: In this study we evaluate the nature of bacteria-PMN
      interaction by assessing ROS production, apoptosis, lipid raft coalescence, and
      phagocytosis induced by Mtb strains. RESULTS: Dectin-1 and TLR2 participate in
      Mtb-induced ROS generation and apoptosis in PMN involving p38 MAPK and Syk
      activation with the participation of a TLR2-dependent coalescence of lipid rafts.
      Further, ROS production occurs during the phagocytosis of non-opsonized bacteria
      and involves alpha-glucans on the capsule. In contrast, strain M lacks the
      ability to induce ROS because of: 1) a reduced phagocytosis and 2) a failure in
      coalescence of lipid raft. CONCLUSIONS: The differences in wall composition could
      explain the success of some strains which stay unnoticed by the host through
      inhibition of apoptosis and ROS but making possible its replication inside PMN as
      a potential evasion mechanism. Innate immune responses elicited by Mtb strain-to
      strain variations need to be considered in TB vaccine development.

PMID- 24886275
TI  - Improvements in pandemic preparedness in 8 Central American countries, 2008-2012.
AB  - BACKGROUND: In view of ongoing pandemic threats such as the recent human cases of
      novel avian influenza A(H7N9) in China, it is important that all countries
      continue their preparedness efforts. Since 2006, Central American countries have
      received donor funding and technical assistance from the U.S. Centers for Disease
      Control and Prevention (CDC) to build and improve their capacity for influenza
      surveillance and pandemic preparedness. Our objective was to measure changes in
      pandemic preparedness in this region, and explore factors associated with these
      changes, using evaluations conducted between 2008 and 2012. METHODS: Eight
      Central American countries scored their pandemic preparedness across 12
      capabilities in 2008, 2010 and 2012, using a standardized tool developed by CDC.
      Scores were calculated by country and capability and compared between evaluation
      years using the Student's t-test and Wilcoxon Rank Sum test, respectively.
      Virological data reported to WHO were used to assess changes in testing capacity
      between evaluation years. Linear regression was used to examine associations
      between scores, donor funding, technical assistance and WHO reporting. RESULTS:
      All countries improved their pandemic preparedness between 2008 and 2012 and
      seven made statistically significant gains (p < 0.05). Increases in median scores
      were observed for all 12 capabilities over the same period and were statistically
      significant for eight of these (p < 0.05): country planning, communications,
      routine influenza surveillance, national respiratory disease surveillance,
      outbreak response, resources for containment, community interventions and health
      sector response. We found a positive association between preparedness scores and
      cumulative funding between 2006 and 2011 (R2 = 0.5, p < 0.01). The number of
      specimens reported to WHO from participating countries increased significantly
      from 5,551 (2008) to 18,172 (2012) (p < 0.01). CONCLUSIONS: Central America has
      made significant improvements in influenza pandemic preparedness between 2008 and
      2012. U.S. donor funding and technical assistance provided to the region is
      likely to have contributed to the improvements we observed, although information
      on other sources of funding and support was unavailable to study. Gains are also
      likely the result of countries' response to the 2009 influenza pandemic. Further
      research is required to determine the degree to which pandemic improvements are
      sustainable.

PMID- 24886277
TI  - TGF beta and IL13 in Schistosomiasis mansoni associated pulmonary arterial
      hypertension; a descriptive study with comparative groups.
AB  - BACKGROUND: It is suggested that interleukin (IL)-13 and transforming growth
      factor (TGF)-beta play a role in the pulmonary vascular changes found in animal
      models of schistosomiasis. The aim of this study was to assess and compare the
      serum levels of total TGF-beta and IL-13 of patients with schistosomiasis with
      pulmonary arterial hypertension (PAH) and patients with schistosomiasis without
      PAH. METHODS: 34 patients from the schistosomiasis outpatient clinic of the
      Hospital das Clinicas, Recife, Pernambuco, Brazil, without PAH assessed by
      echocardiography and 34 patients from the Reference Centre of Pulmonary
      Hypertension of Pronto Socorro Cardiologico de Pernambuco, Recife, Brazil with
      PAH, confirmed by right heart catheterization, were enrolled on the study. Both
      groups presented with schistosomal periportal fibrosis after abdominal
      ultrasound. Serum levels of TGF-beta1 and IL-13 were determined by ELISA. Student
      t test to independent samples, Mann-Whitney test to nonparametric variables,
      Pearson correlation test for correlation analyses and Fisher Chi-squared test to
      compare categorical analyses were used. RESULTS: The median value of TGF-beta1
      was significantly higher in patients with PAH (22496.9 pg/ml, interquartile range
      [IR] 15936.7 - 32087.8) than in patients without PAH (13629.9 pg/ml, IR: 10192.2-
      22193.8) (p = 0.006). There was no difference in the median value of IL-13 in the
      group with Sch-PAH compared to patients without Sch-PAH (p > 0.05). CONCLUSION:
      Our results suggest that TGF-beta possibly plays a role in the pathogenesis of
      schistosomiasis-associated PAH.

PMID- 24886276
TI  - Sensory cortex lesion triggers compensatory neuronal plasticity.
AB  - BACKGROUND: Lesions to the human brain often cause dramatic impairments in the
      life of patients because of the very limited capacity of the mammalian nervous
      system to regenerate. On the other hand, neuronal tissue has a high capacity to
      reorganize itself so that loss of function due to brain damage may be compensated
      through neuroplastic reorganization of undamaged tissue in brain regions adjacent
      or contralateral to the lesion site. In this study we investigated the effect of
      serial lesions of the auditory cortices (AC) in both hemispheres of Mongolian
      gerbils on discrimination performance for fast amplitude modulated tones (AM).
      Healthy animals were trained to discriminate two fast AM, an ability that has
      previously been shown to critically depend on cortical processing. Their ability
      to maintain significant discrimination performance was retested after unilateral
      AC lesion, and again after lesion of the contralateral AC, with 15 days of
      continuing training in between the two lesions. RESULTS: After bilateral cortical
      ablation of both AC and 45 days of training the animals show no change in pure
      tone detection threshold as measured with modulation of the acoustic startle
      reflex which has been shown to rely on subcortical structures. In contrast to
      simultaneous bilateral ablation of AC that results in complete loss of AM
      discrimination ability in this paradigm we found compensatory plasticity that
      seems to be triggered by unilateral cortical ablation with subsequent training
      and that is able to almost fully compensate for the lost cortical functions.
      CONCLUSIONS: Our results demonstrate that AM discrimination ability that normally
      depends on AC may be transferred to other brain regions when the brain has time
      to activate compensatory plasticity between the lesions of the two AC
      hemispheres. For this process to take place obviously one intact AC hemisphere is
      needed. This finding may open perspectives for new therapeutic strategies that
      may alleviate the impairments after multiple ischemic strokes.

PMID- 24886278
TI  - Recovery of an injured corticoreticular pathway via transcallosal fibers in a
      patient with intracerebral hemorrhage.
AB  - BACKGROUND: Several studies have reported on injury of the corticoreticular
      pathway (CRP), however, little is known about the mechanism for recovery of an
      injured CRP. We report on a patient with intracerebral hemorrhage (ICH) who
      showed recovery of an injured CRP via transcallosal fibers, which was
      demonstrated by diffusion tensor tractography (DTT). CASE PRESENTATION: A 67-year
      old man presented with complete paralysis (Medical Research Council: 0/5) of the
      left extremities at the onset of a right putaminal hemorrhage. At six weeks after
      onset, he presented with more severe weakness of proximal joint muscles than
      distal joint muscles (right shoulder abductor; 2-, finger extensor; 3+, hip
      flexor; 2+, ankle dorsiflexor; 3). Although his right hemiplegia had recovered
      well, he consistently showed more severe proximal weakness (right shoulder
      abductor; 3, finger extensor; 4, hip flexor; 3+, ankle dorsiflexor; 4) until 16
      weeks after onset. On both six- and 16-week DTTs, in the left (affected)
      hemisphere, the CRP showed severe narrowing with discontinuation of the anterior
      fibers at the corona radiata on six-week DTT, however, the discontinued anterior
      fibers of the CRP were connected to the right cerebral cortex via transcallosal
      fibers on 16-week DTT. CONCLUSION: We demonstrated recovery of an injured CRP via
      transcallosal fibers in a patient with ICH. We believe that this might be a
      mechanism for recovery of an injured CRP.

PMID- 24886279
TI  - Loop-mediated isothermal amplification (LAMP) assay for the identification of
      Echinococcus multilocularis infections in canine definitive hosts.
AB  - BACKGROUND: Alveolar echinococcosis, caused by the metacestode larval stage of
      Echinococcus multilocularis, is a zoonosis of public health significance and is
      highly prevalent in northwest China. To effectively monitor its transmission, we
      developed a new rapid and cheap diagnostic assay, based on loop-mediated
      isothermal amplification (LAMP), to identify canine definitive hosts infected
      with E. multilocularis. METHODS: The primers used in the LAMP assay were based on
      the mitochondrial nad5 gene of E. multilocularis and were designed using Primer
      Explorer V4 software. The developed LAMP assay was compared with a conventional
      PCR assay, using DNA extracted from the feces of dogs experimentally infected
      with E. multilocularis, on 189 dog fecal samples collected from three E.
      multilocularis-endemic regions in Qinghai province, the People's Republic of
      China, and 30 negative control copro-samples from dogs from an area in Gansu
      province that had been subjected to an intensive de-worming program. Light
      microscopy was also used to examine the experimentally obtained and field
      collected dog copro-samples for the presence of E. multilocularis eggs. RESULTS:
      The E. multilocularis-positivity rates obtained for the field-collected fecal
      samples were 16.4% and 5.3% by the LAMP and PCR assays, respectively, and all
      samples obtained from the control dogs were negative. The LAMP assay was able to
      detect E. multilocularis DNA in the feces of experimentally infected dogs at 12
      days post-infection, whereas the PCR assay was positive on the 17th day and eggs
      were first detectable by light microscopy at day 44 post-challenge. CONCLUSION:
      The earlier specific detection of an E. multilocularis infection in dog copro
      samples indicates that the LAMP assay we developed is a realistic alternative
      method for the field surveillance of canines in echinococcosis-endemic areas.

PMID- 24886280
TI  - Fractionated stereotactic radiosurgery for patients with skull base metastases
      from systemic cancer involving the anterior visual pathway.
AB  - BACKGROUND: To analyze the tumor control, survival outcomes, and toxicity after
      stereotactic radiosurgery (SRS) for skull base metastases from systemic cancer
      involving the anterior visual pathway. PATIENTS AND METHODS: We have analyzed 34
      patients (23 females and 11 males, median age 59 years) who underwent multi
      fraction SRS for a skull base metastasis compressing or in close proximity of
      optic nerves and chiasm. All metastases were treated with frameless LINAC-based
      multi-fraction SRS in 5 daily fractions of 5 Gy each. Local control, distant
      failure, and overall survival were estimated using the Kaplan-Meier method
      calculated from the time of SRS. Prognostic variables were assessed using log
      rank and Cox regression analyses. RESULTS: At a median follow-up of 13 months
      (range, 2-36.5 months), twenty-five patients had died and 9 were alive. The 1
      year and 2-year local control rates were 89% and 72%, and respective actuarial
      survival rates were 63% and 30%. Four patients recurred with a median time to
      progression of 12 months (range, 6-27 months), and 17 patients had new brain
      metastases at distant brain sites. The 1-year and 2-year distant failure rates
      were 50% and 77%, respectively. On multivariate analysis, a Karnofsky performance
      status (KPS) >70 and the absence of extracranial metastases were prognostic
      factors associated with lower distant failure rates and longer survival. After
      multi-fraction SRS, 15 (51%) out of 29 patients had a clinical improvement of
      their preexisting cranial deficits. No patients developed radiation-induced optic
      neuropathy during the follow-up. CONCLUSIONS: Multi-fraction SRS (5 x 5 Gy) is a
      safe treatment option associated with good local control and improved cranial
      nerve symptoms for patients with a skull base metastasis involving the anterior
      visual pathway.

PMID- 24886281
TI  - Predictors of recurrence free survival for patients with stage II and III colon
      cancer.
AB  - BACKGROUND: The aim of this study was to evaluate clinico-pathologic specific
      predictors of recurrence for stage II/III disease. Improving recurrence
      prediction for resected stage II/III colon cancer patients could alter
      surveillance strategies, providing opportunities for more informed use of
      chemotherapy for high risk individuals. METHODS: 871 stage II and 265 stage III
      patients with colon cancers were included. Features studied included surgery
      date, age, gender, chemotherapy, tumor location, number of positive lymph nodes,
      tumor differentiation, and lymphovascular and perineural invasion. Time to
      recurrence was evaluated, using Cox's proportional hazards models. The predictive
      ability of the multivariable models was evaluated using the concordance (c)
      index. RESULTS: For stage II cancer patients, estimated recurrence-free survival
      rates at one, three, five, and seven years following surgery were 98%, 92%, 90%,
      and 89%. Only T stage was significantly associated with recurrence. Estimated
      recurrence-free survival rates for stage III patients at one, three, five, and
      seven years following surgery were 94%, 78%, 70%, and 66%. Higher recurrence
      rates were seen in patients who didn't receive chemotherapy (p = 0.023), with a
      higher number of positive nodes (p < 0.001). The c-index for the stage II model
      was 0.55 and 0.68 for stage III. CONCLUSIONS: Current clinic-pathologic
      information is inadequate for prediction of colon cancer recurrence after
      resection for stage II and IIII patients. Identification and clinical use of
      molecular markers to identify the earlier stage II and III colon cancer patients
      at elevated risk of recurrence are needed to improve prognostication of early
      stage colon cancers.

PMID- 24886283
TI  - Proposing a sequential comparative analysis for assessing multilateral health
      agency transformation and sustainable capacity: exploring the advantages of
      institutional theory.
AB  - BACKGROUND: This article proposes an approach to comparing and assessing the
      adaptive capacity of multilateral health agencies in meeting country and
      individual healthcare needs. Most studies comparing multilateral health agencies
      have failed to clearly propose a method for conducting agency comparisons.
      METHODS: This study conducted a qualitative case study methodological approach,
      such that secondary and primary case study literature was used to conduct case
      study comparisons of multilateral health agencies. RESULTS: Through the proposed
      Sequential Comparative Analysis (SCA), the author found a more effective way to
      justify the selection of cases, compare and assess organizational transformative
      capacity, and to learn from agency success in policy sustainability processes.
      CONCLUSIONS: To more affectively understand and explain why some multilateral
      health agencies are more capable of adapting to country and individual healthcare
      needs, SCA provides a methodological approach that may help to better understand
      why these agencies are so different and what we can learn from successful reform
      processes. As funding challenges continue to hamper these agencies' adaptive
      capacity, learning from each other will become increasingly important.

PMID- 24886282
TI  - Synergic silencing of costimulatory molecules prevents cardiac allograft
      rejection.
AB  - BACKGROUND: While substantial progress has been made in blocking acute transplant
      rejection with the advent of immune suppressive drugs, chronic rejection,
      mediated primarily by recipient antigen presentation, remains a formidable
      problem in clinical transplantation. We hypothesized that blocking co-stimulatory
      pathways in the recipient by induction of RNA interference using small
      interference RNA (siRNA) expression vectors can prolong allogeneic heart graft
      survival. METHOD: Vectors expressing siRNA specifically targeting CD40 and CD80
      were prepared. Recipients (BALB/c mice) were treated with CD40 and/or CD80 siRNA
      expression vectors via hydrodynamic injection. Control groups were injected with
      a scrambled siRNA vector and sham treatment (PBS). After treatment, a fully MHC
      mismatched (BALB/c to C57/BL6) heart transplantation was performed. RESULT:
      Allogeneic heart graft survival (>100 days) was approximately 70% in the mice
      treated simultaneously with CD40 and CD80 siRNA expression vectors with overall
      reduction in lymphocyte interstitium infiltration, vascular obstruction, and
      edema. Hearts transplanted into CD40 or CD80 siRNA vector-treated recipients had
      an increased graft survival time compared to negative control groups, but did not
      survive longer than 40 days. In contrast, allogenic hearts transplanted into
      recipients treated with scrambled siRNA vector and PBS stopped beating within 10
      16 days. Real-time PCR (RT-PCR) and flow cytometric analysis showed an
      upregulation of FoxP3 expression in spleen lymphocytes and a concurrent
      downregulation of CD40 and CD80 expression in splenic dendritic cells of siRNA
      treated mice. Functional suppressive activity of splenic dendritic cells (DCs)
      isolated from tolerant recipients was demonstrated in a mixed lymphocyte reaction
      (MLR). Furthermore, DCs isolated from CD40- and CD80-treated recipients promoted
      CD4+CD25+FoxP3+ regulatory T cell differentiation in vitro. CONCLUSION: This
      study demonstrates that the simultaneous silencing of CD40 and CD80 genes has
      synergistic effects in preventing allograft rejection, and may therefore have
      therapeutic potential in clinical transplantation.

PMID- 24886284
TI  - The COLON study: Colorectal cancer: Longitudinal, Observational study on
      Nutritional and lifestyle factors that may influence colorectal tumour
      recurrence, survival and quality of life.
AB  - BACKGROUND: There is clear evidence that nutrition and lifestyle can modify
      colorectal cancer risk. However, it is not clear if those factors can affect
      colorectal cancer treatment, recurrence, survival and quality of life. This paper
      describes the background and design of the "COlorectal cancer: Longitudinal,
      Observational study on Nutritional and lifestyle factors that may influence
      colorectal tumour recurrence, survival and quality of life" - COLON - study. The
      main aim of this study is to assess associations of diet and other lifestyle
      factors, with colorectal cancer recurrence, survival and quality of life. We
      extensively investigate diet and lifestyle of colorectal cancer patients at
      diagnosis and during the following years; this design paper focusses on the
      initial exposures of interest: diet and dietary supplement use, body composition,
      nutrient status (e.g. vitamin D), and composition of the gut microbiota.
      METHODS/DESIGN: The COLON study is a multi-centre prospective cohort study among
      at least 1,000 incident colorectal cancer patients recruited from 11 hospitals in
      the Netherlands. Patients with colorectal cancer are invited upon diagnosis. Upon
      recruitment, after 6 months, 2 years and 5 years, patients fill out food
      frequency questionnaires; questionnaires about dietary supplement use, physical
      activity, weight, height, and quality of life; and donate blood samples.
      Diagnostic CT-scans are collected to assess cross-sectional areas of skeletal
      muscle, subcutaneous fat, visceral fat and intermuscular fat, and to assess
      muscle attenuation. Blood samples are biobanked to facilitate future analyse of
      biomarkers, nutrients, DNA etc. Analysis of serum 25-hydroxy vitamin D levels,
      and analysis of metabolomic profiles are scheduled. A subgroup of patients with
      colon cancer is asked to provide faecal samples before and at several time points
      after colon resection to study changes in gut microbiota during treatment. For
      all patients, information on vital status is retrieved by linkage with national
      registries. Information on clinical characteristics is gathered from linkage with
      the Netherlands Cancer Registry and with hospital databases. Hazards ratios will
      be calculated for dietary and lifestyle factors at diagnosis in relation to
      recurrence and survival. Repeated measures analyses will be performed to assess
      changes over time in dietary and other factors in relation to recurrence and
      survival.

PMID- 24886285
TI  - Intercentre reproducibility of cardiac apparent diffusion coefficient and
      fractional anisotropy in healthy volunteers.
AB  - BACKGROUND: Diffusion tensor cardiac magnetic resonance (DT-CMR) enables probing
      of the microarchitecture of the myocardium, but the apparent diffusion
      coefficient (ADC) and fractional anisotropy (FA) reported in healthy volunteers
      have been inconsistent. The aim of this study was to validate a stimulated-echo
      diffusion sequence using phantoms, and to assess the intercentre reproducibility
      of in-vivo diffusion measures using the sequence. METHODS AND RESULTS: A
      stimulated-echo, cardiac-gated DT-CMR sequence with a reduced-field-of-view,
      single-shot EPI readout was used at two centres with 3 T MRI scanners. Four
      alkane phantoms with known diffusivities were scanned at a single centre using a
      stimulated echo sequence and a spin-echo Stejskal-Tanner diffusion sequence. The
      median (maximum, minimum) difference between the DT-CMR sequence and Stejskal
      Tanner sequence was 0.01 (0.04, 0.0006) * 10(-3) mm2/s (2%), and between the DT
      CMR sequence and literature diffusivities was 0.02 (0.05, 0.006) * 10(-3) mm2/s
      (4%).The same ten healthy volunteers were scanned using the DT-CMR sequence at
      the two centres less than seven days apart. Average ADC and FA were calculated in
      a single mid-ventricular, short axis slice. Intercentre differences were tested
      for statistical significance at the p < 0.05 level using paired t-tests. The mean
      ADC +/- standard deviation for all subjects averaged over both centres was 1.10
      +/- 0.06 * 10(-3) mm2/s in systole and 1.20 +/- 0.09 * 10-3 mm2/s in diastole; FA
      was 0.41 +/- 0.04 in systole and 0.54 +/- 0.03 in diastole. With similarly-drawn
      regions-of-interest, systolic ADC (difference 0.05 * 10(-3) mm2/s), systolic FA
      (difference 0.003) and diastolic FA (difference 0.01) were not statistically
      significantly different between centres (p > 0.05), and only the diastolic ADC
      showed a statistically significant, but numerically small, difference of 0.07 *
      10(-3) mm2/s (p = 0.047). The intercentre, intrasubject coefficients of variance
      were: systolic ADC 7%, FA 6%; diastolic ADC 7%, FA 3%. CONCLUSIONS: This is the
      first study to demonstrate the accuracy of a stimulated-echo DT-CMR sequence in
      phantoms, and demonstrates the feasibility of obtaining reproducible ADC and FA
      in healthy volunteers at separate centres with well-matched sequences and
      processing.

PMID- 24886286
TI  - On the origins of the mitotic shift in proliferating cell layers.
AB  - BACKGROUND: During plant and animal development, monolayer cell sheets display a
      stereotyped distribution of polygonal cell shapes. In interphase cells these
      shapes range from quadrilaterals to decagons, with a robust average of six sides
      per cell. In contrast, the subset of cells in mitosis exhibits a distinct
      distribution with an average of seven sides. It remains unclear whether this
      'mitotic shift' reflects a causal relationship between increased polygonal
      sidedness and increased division likelihood, or alternatively, a passive effect
      of local proliferation on cell shape. METHODS: We use a combination of
      probabilistic analysis and mathematical modeling to predict the geometry of
      mitotic polygonal cells in a proliferating cell layer. To test these predictions
      experimentally, we use Flp-Out stochastic labeling in the Drosophila wing disc to
      induce single cell clones, and confocal imaging to quantify the polygonal
      topologies of these clones as a function of cellular age. For a more generic test
      in an idealized cell layer, we model epithelial sheet proliferation in a finite
      element framework, which yields a computationally robust, emergent prediction of
      the mitotic cell shape distribution. RESULTS: Using both mathematical and
      experimental approaches, we show that the mitotic shift derives primarily from
      passive, non-autonomous effects of mitoses in neighboring cells on each cell's
      geometry over the course of the cell cycle. Computationally, we predict that
      interphase cells should passively gain sides over time, such that cells at more
      advanced stages of the cell cycle will tend to have a larger number of neighbors
      than those at earlier stages. Validating this prediction, experimental analysis
      of randomly labeled epithelial cells in the Drosophila wing disc demonstrates
      that labeled cells exhibit an age-dependent increase in polygonal sidedness.
      Reinforcing these data, finite element simulations of epithelial sheet
      proliferation demonstrate in a generic framework that passive side-gaining is
      sufficient to generate a mitotic shift. CONCLUSIONS: Taken together, our results
      strongly suggest that the mitotic shift reflects a time-dependent accumulation of
      shared cellular interfaces over the course of the cell cycle. These results
      uncover fundamental constraints on the relationship between cell shape and cell
      division that should be general in adherent, polarized cell layers.

PMID- 24886287
TI  - An exploratory trial of insulin initiation and titration among patients with type
      2 diabetes in the primary care setting with retrospective continuous glucose
      monitoring as an adjunct: INITIATION study protocol.
AB  - BACKGROUND: Insulin initiation and titration in primary care is necessary to
      respond to the growing epidemic of type 2 diabetes (T2D). The INITIATION study
      aims to evaluate the impact of implementing a new model of care with Primary Care
      Physician and Practice Nurse (PN) teams supported by a Credentialed Diabetes
      Educator-Registered Nurse (CDE-RN) and endocrinologist in initiating and
      titrating basal and prandial insulin for T2D patients in the Australian
      healthcare system over 24 weeks. This study also explores the feasibility and
      efficacy of retrospective continuous glucose monitoring (r-CGM) in comparison
      with self-monitoring of blood glucose (SMBG) among people with T2D in primary
      care. METHODS/DESIGN: The study employs a before and after design with a nested
      exploratory trial of SMBG and r-CGM. A total of 102 insulin naive T2D patients
      with a glycated haemoglobin (HbA1c) level of >7.5% in the previous 6 months while
      treated with maximal oral therapy will be recruited and screened from 22 primary
      care practices in Melbourne, Australia. All patients will be commenced on a basal
      insulin regimen following randomization into one of the two blood glucose
      monitoring arms, with intensification to a "basal plus" regimen if required. The
      outcomes of the new model of care will be benchmarked with data collected over
      the same period from a specialist setting in Melbourne, Australia. DISCUSSION:
      This article describes the study protocol and insulin treatment algorithm
      employed in the first study to explore r-CGM use among T2D in primary care.
      Findings from the INITIATION study will inform development of a larger randomized
      controlled trial. TRIAL REGISTRATION: ACTRN12610000797077.

PMID- 24886288
TI  - Secondary reproduction in the herbaceous monocarp Lobelia inflata: time
      constrained primary reproduction does not result in increased deferral of
      reproductive effort.
AB  - BACKGROUND: Although semelparity is a life history characterized by a single
      reproductive episode within a single reproductive season, some semelparous
      organisms facultatively express a second bout of reproduction, either in a
      subsequent season ("facultative iteroparity") or later within the same season as
      the primary bout ("secondary reproduction"). Secondary reproduction has been
      explained as the adaptive deferral of reproductive potential under circumstances
      in which some fraction of reproductive success would otherwise have been lost
      (due, for example, to inopportune timing). This deferral hypothesis predicts a
      positive relationship between constraints on primary reproduction and expression
      of secondary reproduction. The herbaceous monocarp Lobelia inflata has been
      observed occasionally to express a secondary reproductive episode in the field.
      However, it is unknown whether secondary reproduction is an example of adaptive
      reproductive deferral, or is more parsimoniously explained as the vestigial
      expression of iteroparity after a recent transition to semelparity. Here, we
      experimentally manipulate effective season length in each of three years to test
      whether secondary reproduction is a form of adaptive plasticity consistent with
      the deferral hypothesis. RESULTS: Our results were found to be inconsistent with
      the adaptive deferral explanation: first, plants whose primary reproduction was
      time-constrained exhibited decreased (not increased) allocation to subsequent
      secondary reproduction, a result that was consistent across all three years;
      second, secondary offspring-although viable in the laboratory-would not have the
      opportunity for expression under field conditions, and would thus not contribute
      to reproductive success. CONCLUSIONS: Although alternative adaptive explanations
      for secondary reproduction cannot be precluded, we conclude that the
      characteristics of secondary reproduction found in L. inflata are consistent with
      predictions of incomplete or transitional evolution to annual semelparity.

PMID- 24886289
TI  - Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive
      ductal carcinoma of the breast.
AB  - BACKGROUND: 11q13 region is a frequently amplified locus in human malignancies.
      Among the genes located in this region, FADD is one of the alleged driving genes.
      Because amplification is not generally confined to a single gene and amplified
      genes may not show increased expression, we need to evaluate clinical
      significance of changes occurring in 11q13 region to understand their roles in
      carcinogenesis. Therefore, we screened expressions of FADD and closely located
      genes (PPFIA1 and TMEM16A) and evaluated the expressions to find clinical
      significance in invasive ductal carcinoma of the breast. METHODS: Ninety-eight
      cases of invasive ductal carcinoma of the breast were collected. Using archival
      tissues resected from the cases, we built a tissue microarray and used it in
      immunohistochemistry. We evaluated the association of FADD, PPFIA1, and TMEM16A
      expression scores with clinicopathological parameters, including disease-free
      survival. RESULTS: FADD expression was associated with T stage (P=0.046). The
      combined score of FADD, PPFIA1, and TMEM16A gene expressions was associated with
      perineural invasion (P=0.022). Although individual gene expressions of TMEM16A,
      FADD, and PPFIA1 failed to show significant association with disease-free
      survival, combined gene expression scores did show association with disease-free
      survival (P=0.034). CONCLUSIONS: FADD, TMEM16A, and PPFIA1 gene expressions as a
      whole were associated with disease-free survival in breast cancer.

PMID- 24886290
TI  - LOX-1 and ROS, inseparable factors in the process of endothelial damage.
AB  - Lectin-like oxidized low-density lipoprotein (LOX-1) has been identified in
      endothelial cells as the main receptor of oxidized low-density lipoprotein
      (OxLDL). LOX-1 is upregulated in the presence of pathological conditions
      including atherosclerosis, hypertension, and diabetes because it acts as a
      mediator of "endothelial dysfunction". It promotes the generation of superoxide
      anion (O2(-)), the inhibition of nitric oxide (NO) production and the increment
      of endothelial adhesiveness to monocytes. Recently, it was reported that OxLDL,
      binding to LOX-1, determined a significant increase in the generation of reactive
      oxygen species (ROS), suggesting the involvement of signaling pathways such as
      mitogen-activated protein kinases (MAPKs). It is now generally accepted that ROS
      act indirectly on the modulation of LOX-1 expression because ROS oxidize native
      LDL. Moreover, LOX-1 activation per se may stimulate ROS generation. Accordingly,
      our findings showed that high levels of ROS can directly increase LOX-1
      production in microvascular endothelial cells (HMEC-1). It has been reported that
      OxLDL, usually > 20 MUg protein/ml, induced apoptosis in a variety of cell types.
      At low concentrations (< 5 MUg protein/ml) OxLDL appears to be associated with
      cell proliferation and low levels of ROS-induced capillary tube formation in
      endothelial cells. Our data and those of the literature indicate the existence of
      a direct control of LOX-1 by ROS. Although ROS in large amounts clearly have
      detrimental effects on cell biology, small amounts of ROS could have a beneficial
      effect, suggesting its therapeutic potential for reducing ischemic tissue.

PMID- 24886291
TI  - Phospholipids from herring roe improve plasma lipids and glucose tolerance in
      healthy, young adults.
AB  - BACKGROUND: Herring roe is an underutilized source of n-3 polyunsaturated fatty
      acids (PUFAs) for human consumption with high phospholipid (PL) content. Studies
      have shown that PL may improve bioavailability of n-3 PUFAs. Arctic Nutrition's
      herring roe product MOPLTM30 is a PL: docosahexaenoic acid (DHA)-rich fish oil
      mixture, with a DHA:eicosapentaenoic acid (EPA) ratio of about 3:1, which is also
      rich in choline. In this pilot study, we determined if MOPL30 could favorably
      affect plasma lipid parameters and glucose tolerance in healthy young adults.
      METHODS: Twenty female and one male adults, between 22 and 26 years of age,
      participated in the study. Participants took encapsulated MOPL30, 2.4 g/d EPA +
      DHA, for 14 days, and completed a three-day weighed food record before and during
      the capsule intake. Plasma lipids and their fatty acid (FA) composition, plasma
      and red blood cell (RBC) phosphatidylcholine (PC) FA composition, acylcarnitines,
      choline, betaine and insulin were measured before and after supplementation (n =
      21), and one and four weeks after discontinuation of supplementation (n = 14). An
      oral glucose tolerance test was performed before and after supplementation.
      RESULTS: Fasting plasma triacylglycerol and non-esterified fatty acids decreased
      and HDL-cholesterol increased after 14 days of MOPL30 intake (p < 0.05). The
      dietary records showed that PUFA intake prior to and during capsule intake was
      not different. Fasting plasma glucose was unchanged from before to after
      supplementation. However, during oral glucose tolerance testing, blood glucose at
      both 10 and 120 min was significantly lower after supplementation with MOPL30
      compared to baseline measurements. Plasma free choline and betaine were
      increased, and the n-6/n-3 polyunsaturated (PUFA) ratio in plasma and RBC PC were
      decreased post-supplementation. Four weeks after discontinuation of MOPL30, most
      parameters had returned to baseline, but a delayed effect was observed on n-6
      PUFAs. CONCLUSIONS: Herring roe rich in PL improved the plasma lipid profile and
      glycemic control in young adults with an overall healthy lifestyle.

PMID- 24886292
TI  - A case report of Charcot arthropathy caused by syringomyelia and Chiari
      malformation complicated with scoliosis.
AB  - BACKGROUND: Although Charcot arthropathy, also known as neuropathic arthropathy,
      of which early diagnosis and treatment is extremely difficult, associated with
      other cause factor has been widely described, Charcot arthropathy caused by
      syringomyelia and Chiari malformation complicated with scoliosis has never been
      described in the literature. CASE PRESENTATION: A 44-year-old male was
      hospitalized for diagnosis and treatment due to complaining the progressively
      swelling and limitation of motion in his left shoulder joint for 1 year. The
      patient has no significant past medical history except for scoliosis 8 years
      prior to his presentation to our clinic; He denied any constitutional symptoms,
      trauma, or pain in the upper extremities at this time of presentation. Based on
      history, physical and auxiliary examination, following diagnoses were made:
      Charcot arthropathy of the left shoulder, syringomyelia, Chiari malformation and
      scoliosis. CONCLUSION: Once Charcot arthritis was found, it was mostly in
      advanced stage and very difficult to treat. So we recommended that if patient
      suffering from scoliosis visited in clinic, further examination such as magnetic
      resonance imaging (MRI) and regular follow-up should be carried out, and early
      stage of this devastating disease caused by syringomyelia and Chiari malformation
      may be diagnosed easily.

PMID- 24886293
TI  - Salivary glands harbor more diverse microbial communities than gut in Anopheles
      culicifacies.
AB  - BACKGROUND: In recent years, it has been well documented that gut flora not only
      influence mosquito physiology, but also significantly alter vector competency.
      Although, salivary gland and gut constitute key partners of the digestive system,
      it is still believed that salivary glands may harbor less flora than gut (Parasit
      Vectors 6: 146, 2013). METHODS: Using a metagenomic approach, we have identified
      for the first time the diverse microbial community associated with these two
      physiologically different tissues of the digestive system in the mosquito
      Anopheles culicifacies. RESULTS: A total of 17 different phyla could be assigned
      to the whole metagenomic dataset, predominated by the phylum Proteobacteria,
      Firmicutes, Bacteriodetes, Tenericutes and Actinomycetes. Common bacteria
      included the members of Enhydrobacter, Agromonas, Serratia, Ralsonia,
      Lactobacillus, Pseudomonas, Streptococcus, Rubrobacter, Anaerococcus,
      Methylobacterium, Turicibacter, Elizabethkingia etc. in both the tissues
      representing 'core microbiota' of the mosquito digestive system. Salivary
      associated unique bacterial community included the members of Chloriflexi,
      Chlorobi, Cyanobacteria, Nitrospira, TM7, Armatimonadetes, Planctomycetes,
      Fibrobacteres etc. CONCLUSION: We find that the salivary gland microbial
      community structure is more diverse than gut of the mosquito, probably due to
      differential feeding associated engagements such as food acquisition, ingestion
      and digestion processes.

PMID- 24886294
TI  - PAR2-mediated upregulation of BDNF contributes to central sensitization in bone
      cancer pain.
AB  - BACKGROUND: Bone cancer pain is currently a major clinical challenge for the
      management of cancer patients, and the cellular and molecular mechanisms
      underlying the spinal sensitization remain unclear. While several studies
      demonstrated the critical role of proteinase-activated receptor (PAR2) in the
      pathogenesis of several types of inflammatory or neuropathic pain, the
      involvement of spinal PAR2 and the pertinent signaling in the central
      sensitization is not determined yet in the rodent model of bone cancer pain.
      FINDINGS: Implantation of tumor cells into the tibias induced significant thermal
      hyperalgesia and mechanical allodynia, and enhanced glutamatergic strength in the
      ipsilateral dorsal horn. Significantly increased brain-derived neurotrophic
      factor (BDNF) expression was detected in the dorsal horn, and blockade of spinal
      BDNF signaling attenuated the enhancement of glutamatergic strength, thermal
      hyperalgesia and mechanical allodynia in the rats with bone cancer pain.
      Significantly increased spinal PAR2 expression was also observed, and inhibition
      of PAR2 signaling ameliorated BDNF upsurge, enhanced glutamatergic strength, and
      thermal hyperalgesia and mechanical allodynia. Inhibition of NF-kappaB pathway,
      the downstream of PAR2 signaling, also significantly decreased the spinal BDNF
      expression, glutamatergic strength of dorsal horn neurons, and thermal
      hyperalgesia and mechanical allodynia. CONCLUSION: The present study demonstrated
      that activation of PAR2 triggered NF-kappaB signaling and significantly
      upregulated the BDNF function, which critically contributed to the enhancement of
      glutamatergic transmission in spinal dorsal horn and thermal and mechanical
      hypersensitivity in the rats with bone cancer. This indicated that PAR2 - NF
      kappaB signaling might become a novel target for the treatment of pain in
      patients with bone cancer.

PMID- 24886295
TI  - Quantitative trait loci identification, fine mapping and gene expression
      profiling for ovicidal response to whitebacked planthopper (Sogatella furcifera
      Horvath) in rice (Oryza sativa L.).
AB  - BACKGROUND: The whitebacked planthopper (WBPH), Sogatella furcifera Horvath, is a
      serious rice pest in Asia. Ovicidal resistance is a natural rice defense
      mechanism against WBPH and is characterized by the formation of watery lesions
      (WLs) and increased egg mortality (EM) at the WBPH oviposition sites. RESULTS:
      This study aimed to understand the genetic and molecular basis of rice ovicidal
      resistance to WBPH by combining genetic and genomic analyses. First, the ovicidal
      trait in doubled haploid rice lines derived from a WBPH-resistant cultivar (CJ06)
      and a WBPH-susceptible cultivar (TN1) were phenotyped based on the necrotic
      symptoms of the leaf sheaths and EM. Using a constructed molecular linkage map,
      19 quantitative trait loci (QTLs) associated with WLs and EM were identified on
      eight chromosomes. Of them, qWL6 was determined to be a major QTL for WL. Based
      on chromosome segment substitution lines and a residual heterozygous population,
      a high-resolution linkage analysis further defined the qWL6 locus to a 122-kb
      region on chromosome 6, which was annotated to encode 20 candidate genes. We then
      conducted an Affymetrix microarray analysis to determine the transcript abundance
      in the CJ06 and TN1 plants. Upon WBPH infestation, 432 genes in CJ06 and 257
      genes in TN1 were significantly up-regulated, while 802 genes in CJ06 and 398
      genes in TN1 were significantly down-regulated. This suggests that remarkable
      global changes in gene expression contribute to the ovicidal resistance of rice.
      Notably, four genes in the 122-kb region of the qWL6 locus were differentially
      regulated between CJ06 and TN1 in response to the WBPH infestation, suggesting
      they may be candidate resistance genes. CONCLUSIONS: The information obtained
      from the fine mapping of qWL6 and the microarray analyses will facilitate the
      isolation of this important resistance gene and its use in breeding WBPH
      resistant rice.

PMID- 24886296
TI  - Repair of orbital bone defects in canines using grafts of enriched autologous
      bone marrow stromal cells.
AB  - BACKGROUND: Bone tissue engineering is a new approach for the repair of orbital
      defects. The aim of the present study was to explore the feasibility of tissue
      engineered bone constructed using bone marrow stromal cells (BMSCs) that were
      rapidly isolated and concentrated from bone marrow (BM) by the red cell lysis
      method, then combined with beta-tricalcium phosphate (beta-TCP) to create grafts
      used to restore orbital bone defects in canines. METHODS: In the experimental
      group, grafts were constructed using BMSCs obtained by red cell lysis from 20 ml
      bone marrow, combined with beta-TCP and BM via the custom-made stem cell-scaffold
      device, then used to repair 10 mm diameter medial orbital wall bony defects in
      canines. Results were compared with those in groups grafted with BM/beta-TCP or
      beta-TCP alone, or with defects left untreated as controls. The enrichment of
      BMSCs and nucleated cells (NCs) in the graft was calculated from the number in
      untreated bone marrow and in suspensions after red cell lysis. Spiral computed
      tomography (CT) scans were performed 1, 4, 12 and 24 weeks after implantation in
      all groups. Gross examination, micro-CT and histological measurements were
      performed 24 weeks after surgery. The results were analyzed to evaluate the
      efficacy of bone repair. RESULTS: The number of NCs and of colony-forming units
      within the scaffolds were increased 54.8 times and 53.4 times, respectively,
      compared with untreated bone marrow. In the BMSC-BM/beta-TCP group, CT
      examination revealed that the scaffolds were gradually absorbed and the bony
      defects were restored. Micro-CT and histological examination confirmed that the
      implantations led to good repair of the defects, with 6 out 8 orbital defects
      completely restored in the experimental group, while by contrast, the grafts in
      the control groups did not fully repair the bony defects, a difference which was
      statistically significant (p<0.05). CONCLUSIONS: Tissue-engineered bone,
      constructed using BMSCs isolated by red cell lysis of BM, can restore critical
      sized orbital wall defects in canines.

PMID- 24886297
TI  - Psychometric properties of a sign language version of the Mini International
      Neuropsychiatric Interview (MINI).
AB  - BACKGROUND: There is a need for psychiatric assessment instruments that enable
      reliable diagnoses in persons with hearing loss who have sign language as their
      primary language. The objective of this study was to assess the validity of the
      Norwegian Sign Language (NSL) version of the Mini International Neuropsychiatric
      Interview (MINI). METHODS: The MINI was translated into NSL. Forty-one signing
      patients consecutively referred to two specialised psychiatric units were
      assessed with a diagnostic interview by clinical experts and with the MINI. Inter
      rater reliability was assessed with Cohen's kappa and "observed agreement".
      RESULTS: There was 65% agreement between MINI diagnoses and clinical expert
      diagnoses. Kappa values indicated fair to moderate agreement, and observed
      agreement was above 76% for all diagnoses. The MINI diagnosed more co-morbid
      conditions than did the clinical expert interview (mean diagnoses: 1.9 versus
      1.2). Kappa values indicated moderate to substantial agreement, and "observed
      agreement" was above 88%. CONCLUSION: The NSL version performs similarly to other
      MINI versions and demonstrates adequate reliability and validity as a diagnostic
      instrument for assessing mental disorders in persons who have sign language as
      their primary and preferred language.

PMID- 24886298
TI  - The development of endometrial hyperplasia in aged PD-1-deficient female mice.
AB  - BACKGROUND: Programmed death-1 (PD-1, Pdcd1)-deficient mice develop different
      types of autoimmune diseases depending on the mouse strain but its role in uterus
      development has not been reported. METHODS: In this study, the expression of PD-1
      and its ligands, PD-L1 and PD-L2, in uterine tissues from aged WT mice in a
      129svEv-Brd background was analyzed by immunohistochemistry and the uterine
      morphology between WT and PD-1-/- mice was compared by hematoxylin and eosin
      staining. RESULTS: The aged PD-1-/- female mice in a 129svEv-Brd rather than
      Balb/c background develop endometrial hyperplasia. H&E staining showed an
      increase in the number of glands, neovascularization and an extremely large
      luminal cavity in aged PD-1-/- uteri. Immunohistochemical assay showed that the
      expression of PD-1 was observed in glandular/luminal epithelium and cells
      infiltrating the stroma. Fluorescent double staining demonstrated that PD-1
      expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and
      CK-18+ epithelial cells, respectively. Additionally, PD-1 co-expresses with
      vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an
      accumulation of glandular/luminal epithelium derived VEGF, which accelerates the
      expression of the proliferation-associated protein, proliferating cell nuclear
      antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD
      1-/- uteri. CONCLUSIONS: These findings showed that PD-1 deficiency augments
      luminal epithelial cell proliferation probably through induced VEGF secretion,
      suggesting PD-1 plays an important role in controlling the growth and
      differentiation of the uterine epithelium. VIRTUAL SLIDES: The virtual slide(s)
      for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905.

PMID- 24886299
TI  - DNA microarray-based detection of Coxiella burnetii, the causative agent of Q
      fever.
AB  - BACKGROUND: An easy-to-handle microarray assay based on the cost-effective
      ArrayTubeTM platform has been designed for the rapid and unequivocal
      identification of Coxiella burnetii, the causative agent of Q fever. The gene
      targets include the chromosomally coded markers icd, omp/com1, and IS1111 as well
      as the plasmid coded markers cbbE and cbhE. RESULTS: A representative panel
      comprising 50 German C. burnetii isolates and 10 clinical samples was examined to
      validate the test. All tested isolates harboured plasmid QpH1 and were correctly
      identified, corresponding to 100% sensitivity. The assay's limit of detection was
      100 genome equivalents (GE) for icd, omp/com1, cbbE and cbhE and 10 GE for
      IS1111. Assay specificity was 100% as determined by analysing a panel of 37 non
      Coxiella strains. CONCLUSIONS: The present array is a rational assembly of
      established and evaluated targets for the rapid and unequivocal detection of C.
      burnetii. This array could be applied to the screening of vaginal swabs from
      small ruminants; screening of environmental samples e.g. on farms or screening of
      human samples.

PMID- 24886301
TI  - Viral persistence in colorectal cancer cells infected by Newcastle disease virus.
AB  - BACKGROUND: Newcastle disease virus (NDV), a single-stranded RNA virus of the
      family Paramyxoviridae, is a candidate virotherapy agent in cancer treatment.
      Promising responses were observed in clinical studies. Despite its high
      potential, the possibility of the virus to develop a persistent form of infection
      in cancer cells has not been investigated. Occurrence of persistent infection by
      NDV in cancer cells may cause the cells to be less susceptible to the virus
      killing. This would give rise to a population of cancer cells that remains viable
      and resistant to treatment. RESULTS: During infection experiment in a series of
      colorectal cancer cell lines, we adventitiously observed a development of
      persistent infection by NDV in SW480 cells, but not in other cell lines tested.
      This cell population, designated as SW480P, showed resistancy towards NDV killing
      in a re-infection experiment. The SW480P cells retained NDV genome and produced
      virus progeny with reduced plaque forming ability. CONCLUSION: These observations
      showed that NDV could develop persistent infection in cancer cells and this
      factor needs to be taken into consideration when using NDV in clinical settings.

PMID- 24886300
TI  - Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and
      memory impairment.
AB  - BACKGROUND: Systemic bacterial infections often result in enduring cognitive
      impairment and are a risk factor for dementia. There are currently no effective
      treatments for infection-induced cognitive impairment. Previous studies have
      shown that intermittent fasting (IF) can increase the resistance of neurons to
      injury and disease by stimulating adaptive cellular stress responses. However,
      the impact of IF on the cognitive sequelae of systemic and brain inflammation is
      unknown. METHODS: Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide
      (LPS) or saline intravenously. Half of the rats were subjected to behavioral
      tests and the other half were euthanized two hours after LPS administration and
      the hippocampus was dissected and frozen for analyses. RESULTS: Here, we report
      that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism
      involving NF-kappaB activation, suppression of the expression of pro-inflammatory
      cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS
      resulted in deficits in cognitive performance in the Barnes maze and inhibitory
      avoidance tests, without changing locomotor activity, that were ameliorated in
      rats that had been maintained on the IF diet. IF also resulted in reduced levels
      of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase
      (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL
      1alpha, IL-1beta and TNF-alpha levels, and prevented the LPS-induced reduction of
      BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced
      elevations of serum IL-1beta, IFN-gamma, RANTES, TNF-alpha and IL-6 levels.
      CONCLUSIONS: Taken together, our results suggest that IF induces adaptive
      responses in the brain and periphery that can suppress inflammation and preserve
      cognitive function in an animal model of systemic bacterial infection.

PMID- 24886302
TI  - Procalcitonin and C-reactive protein in urinary tract infection diagnosis.
AB  - BACKGROUND: Urinary infections are a common type of pediatric disease, and their
      treatment and prognosis are closely correlated with infection location. Common
      clinical manifestations and laboratory tests are insufficient to differentiate
      between acute pyelonephritis and lower urinary tract infection. This study was
      conducted to explore a diagnostic method for upper and lower urinary tract
      infection differentiation. METHODS: The diagnostic values of procalcitonin (PCT)
      and C-reactive protein (CRP) were analyzed using the receiver operating
      characteristic curve method for upper and lower urinary tract infection
      differentiation. PCT was determined using chemiluminescent immunoassay. RESULTS:
      The PCT and CRP values in children with acute pyelonephritis were significantly
      higher than those in children with lower urinary tract infection (3.90 +/- 3.51
      ng/ml and 68.17 +/- 39.42 mg/l vs. 0.48 +/- 0.39 ng/ml and 21.39 +/- 14.92 mg/l).
      The PCT values were correlated with the degree of renal involvement, whereas the
      CRP values failed to show such a significant correlation. PCT had a sensitivity
      of 90.47% and a specificity of 88% in predicting nephropathia, whereas CRP had
      sensitivity of 85.71% and a specificity of 48%. CONCLUSIONS: Both PCT and CRP can
      be used for upper and lower urinary tract infection differentiation, but PCT has
      higher sensitivity and specificity in predicting pyelonephritis than CRP. PCT
      showed better results than CRP. PCT values were also correlated with the degree
      of renal involvement.

PMID- 24886303
TI  - Heart rate at 4 s after the onset of exercise in endurance-trained men.
AB  - It has been suggested that the increase in heart rate (HR) at the onset of
      exercise is caused by vagal withdrawal. In fact, endurance runners show a lower
      HR in maximum aerobic tests. However, it is still unknown whether endurance
      runners have a lower HR at 4 s after the onset of exercise (4th-sec-HR). We
      sought to measure the HR at the onset of the 4 s exercise test (4-sET),
      clarifying its relationship to heart rate variability (HRV), spectral indices,
      and cardiac vagal index (CVI) in endurance runners (ER) and healthy untrained
      controls (CON). HR at 4th-sec-HR, CVI, and percent HR increase during exercise
      were analyzed in the 4-sET. High frequency spectrum (HF-nu), low frequency
      spectrum (LF-nu), and low frequency/high frequency band ratio (LF/HF) were
      analyzed from the HRV. ER showed a significantly higher HF, and both a lower LF
      and LF/HF ratio compared with the CON. ER presented a significantly lower 4th-sec
      HR, although neither CVI nor HR increases during exercise were statistically
      different from the CON. In conclusion, ER presented a lower 4th-sec-HR secondary
      to increased vagal influence over the sinus node. CVI seems to be too weak to use
      for discriminating individuals with respect to the magnitude of HR vagal control.

PMID- 24886304
TI  - Evaluation of high throughput gene expression platforms using a genomic biomarker
      signature for prediction of skin sensitization.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) develops upon exposure to certain
      chemical compounds termed skin sensitizers. To reduce the occurrence of skin
      sensitizers, chemicals are regularly screened for their capacity to induce
      sensitization. The recently developed Genomic Allergen Rapid Detection (GARD)
      assay is an in vitro alternative to animal testing for identification of skin
      sensitizers, classifying chemicals by evaluating transcriptional levels of a
      genomic biomarker signature. During assay development and biomarker
      identification, genome-wide expression analysis was applied using microarrays
      covering approximately 30,000 transcripts. However, the microarray platform
      suffers from drawbacks in terms of low sample throughput, high cost per sample
      and time consuming protocols and is a limiting factor for adaption of GARD into a
      routine assay for screening of potential sensitizers. With the purpose to
      simplify assay procedures, improve technical parameters and increase sample
      throughput, we assessed the performance of three high throughput gene expression
      platforms--nCounter(r), BioMark HDTM and OpenArray(r)--and correlated their
      performance metrics against our previously generated microarray data. We measured
      the levels of 30 transcripts from the GARD biomarker signature across 48 samples.
      Detection sensitivity, reproducibility, correlations and overall structure of
      gene expression measurements were compared across platforms. RESULTS: Gene
      expression data from all of the evaluated platforms could be used to classify
      most of the sensitizers from non-sensitizers in the GARD assay. Results also
      showed high data quality and acceptable reproducibility for all platforms but
      only medium to poor correlations of expression measurements across platforms. In
      addition, evaluated platforms were superior to the microarray platform in terms
      of cost efficiency, simplicity of protocols and sample throughput. CONCLUSIONS:
      We evaluated the performance of three non-array based platforms using a limited
      set of transcripts from the GARD biomarker signature. We demonstrated that it was
      possible to achieve acceptable discriminatory power in terms of separation
      between sensitizers and non-sensitizers in the GARD assay while reducing assay
      costs, simplify assay procedures and increase sample throughput by using an
      alternative platform, providing a first step towards the goal to prepare GARD for
      formal validation and adaption of the assay for industrial screening of potential
      sensitizers.

PMID- 24886305
TI  - A qualitative examination of the perceptions of parents on the Canadian Sedentary
      Behaviour Guidelines for the early years.
AB  - BACKGROUND: Minimizing sedentary behavior, in particular screen-based sedentary
      behavior, during the early years is important for healthy growth and development.
      Consequently, new Canadian Sedentary Behaviour Guidelines for the Early Years
      (aged 0-4 years) were recently released. Researchers are unclear what messages
      should supplement the guidelines when disseminating them to parents and when
      using the guidelines in behaviour-change interventions to increase adoption. The
      objective of this study was to qualitatively examine parents' perceptions of the
      new Canadian Sedentary Behaviour Guidelines for the Early Years. METHODS: Parents
      with a child <=4 years who attended a child care centre were purposefully
      recruited from child care centres. A total of 7 semi-structured focus groups with
      2 to 5 parents were conducted from August to November, 2013 by a trained and
      experienced moderator. Participants were asked a series of open-ended questions
      pertaining to the Sedentary Behaviour Guidelines information sheet. Initial
      themes were identified followed by further review and analysis. RESULTS: For the
      most part parents thought the guidelines were clear and did not disagree with the
      recommendations per se. However, some confusion arose around the value of some
      sedentary activities, such as reading and coloring, for social and cognitive
      development. Many parents described feeling guilty after reading the guidelines
      and perceived several barriers in meeting the daily recommendations. Common
      barriers included the need to balance multiple demands of family life, the
      prevalence and accessibility of screen technology, and the weather and built
      environment where families live. Parents expressed the importance of
      communicating the guidelines early enough for good habits to be established and
      the need for realistic strategies and ideas to help them meet the
      recommendations. CONCLUSIONS: Overall the findings indicate that gain-framed
      messages around the role of screen-based and non-screen-based sedentary behavior
      for children's cognitive and social development might be most effective for
      adoption of the guidelines. Furthermore, providing parents the guidelines early
      with resources for minimizing sedentary behavior should also be considered.
      Future research is needed in other demographic groups of parents to confirm these
      findings.

PMID- 24886306
TI  - Functional food awareness and perceptions in relation to information sources in
      older adults.
AB  - BACKGROUND: The functional food industry has experienced innovative and economic
      expansion, yet research into consumer perceptions of functional foods and their
      associated health claims is limited. Among consumers, older adults could benefit
      from functional foods due to age-related issues pertaining to food and health.
      The purpose of this research was to identify the need for information related to
      functional foods among older adults (>=60 years old) and to assess awareness and
      perceptions of health claims on functional food packages. METHODS: Community
      dwelling older adults (n = 200) completed a researcher administered questionnaire
      designed to collect information about functional foods including current
      consumption, motivating factors for consumption, perceived need for information,
      sources of information for functional foods and awareness of health claims.
      RESULTS: Prevalence of functional food consumption among participants was 93.0%.
      Increased awareness and knowledge was the most commonly reported factor that
      would promote functional food consumption (85.5%) and 63.5% of participants
      wanted more information about functional foods with preferred sources being
      newspapers/magazines/books (68.5%) and food labels (66.1%). Participants were
      predominately (93.5%) aware of health claims on functional foods and those with
      more education were more likely to report being aware of health claims (p =
      0.045). CONCLUSIONS: Although functional food consumption among older adults in
      this sample is high, there is a need for further information regarding functional
      foods. These results inform stakeholders regarding the potential for information
      to influence functional food acceptance among older adult consumers.

PMID- 24886307
TI  - Engineering Escherichia coli K12 MG1655 to use starch.
AB  - BACKGROUND: To attain a sustainable bioeconomy, fuel, or valuable product,
      production must use biomass as substrate. Starch is one of the most abundant
      biomass resources and is present as waste or as a food and agroindustry by
      product. Unfortunately, Escherichia coli, one of the most widely used
      microorganisms in biotechnological processes, cannot use starch as a carbon
      source. RESULTS: We engineered an E. coli strain capable of using starch as a
      substrate. The genetic design employed the native capability of the bacterium to
      use maltodextrins as a carbon source plus expression and secretion of its
      endogenous alpha-amylase, AmyA, in an adapted background. Biomass production
      improved using 35% dissolved oxygen and pH 7.2 in a controlled bioreactor.
      CONCLUSION: The engineered E. coli strain can use starch from the milieu and open
      the possibility of optimize the process to use agroindustrial wastes to produce
      biofuels and other valuable chemicals.

PMID- 24886308
TI  - Population-based incidence trends of oropharyngeal and oral cavity cancers by sex
      among the poorest and underprivileged populations.
AB  - BACKGROUND: Oral cancer is an important health issue, with changing incidence in
      many countries. Oropharyngeal cancer (OPC, in tonsil and oropharygeal areas) is
      increasing, while oral cavity cancer (OCC, other sites in the mouth) is
      decreasing. There is the need to identify high risk groups and communities for
      further study and intervention. The objective of this study was to determine how
      the incidence of OPC and OCC varied by neighbourhood socioeconomic status (SES)
      in British Columbia (BC), including the magnitude of any inequalities and
      temporal trends. METHODS: ICDO-3 codes were used to identify OPC and OCC cases in
      the BC Cancer Registry from 1981-2010. Cases were categorized by postal codes
      into SES quintiles (q1-q5) using VANDIX, which is a census-based, multivariate
      weighted index based on neighbourhood average household income, housing tenure,
      educational attainment, employment and family structure. Age-standardized
      incidence rates were determined for OPC and OCC by sex and SES quintiles and
      temporal trends were then examined. RESULTS: Incidence rates are increasing in
      both men and women for OPC, and decreasing in men and increasing in women for
      OCC. This change is not linear or proportionate between different SES quintiles,
      for there is a sharp and dramatic increase in incidence according to the
      deprivation status of the neighbourhood. The highest incidence rates in men for
      both OPC and OCC were observed in the most deprived SES quintile (q5), at 1.7
      times and 2.2 times higher, respectively, than men in the least deprived quintile
      (q1). For OPC, the age-adjusted incidence rates significantly increased in all
      SES quintiles with the highest increase observed in the most deprived quintile
      (q5). Likewise, the highest incidence rates for both OPC and OCC in women were
      observed in the most deprived SES quintile (q5), at 2.1 times and 1.8 times
      higher, respectively, than women in the least deprived quintile (q1). CONCLUSION:
      We report on SES disparities in oral cancer, emphasizing the need for community
      based interventions that address access to medical care and the distribution of
      educational and health promotion resources among the most SES deprived
      communities in British Columbia.

PMID- 24886310
TI  - Contralateral extradural hematoma following decompressive craniectomy for acute
      subdural hematoma (the value of intracranial pressure monitoring): a case report.
AB  - INTRODUCTION: Decompressive surgery for acute subdural hematoma leading to
      contralateral extradural hematoma is an uncommon event with only few cases
      previously reported in the English medical literature. CASE PRESENTATION: The
      present study describes the case of a 39-year-old White Brazilian man who had a
      motorcycle accident; he underwent decompressive craniectomy for the treatment of
      acute subdural hematoma and evolved contralateral extradural hematoma following
      surgery. CONCLUSION: The present case highlights the importance of close
      monitoring of the intracranial pressure of severe traumatic brain injury, even
      after decompressive procedures, because of the possible development of
      contralateral extradural hematoma.

PMID- 24886309
TI  - Characterization of necrosis-inducing NLP proteins in Phytophthora capsici.
AB  - BACKGROUND: Effector proteins function not only as toxins to induce plant cell
      death, but also enable pathogens to suppress or evade plant defense responses.
      NLP-like proteins are considered to be effector proteins, and they have been
      isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing
      evidence that NLPs have the ability to induce cell death and ethylene
      accumulation in plants. RESULTS: We evaluated the expression patterns of 11
      targeted PcNLP genes by qRT-PCR at different time points after infection by P.
      capsici. Several PcNLP genes were strongly expressed at the early stages in the
      infection process, but the expression of other PcNLP genes gradually increased to
      a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14
      showed the highest expression levels during infection by P. capsici. The necrosis
      inducing activity of all targeted PcNLP genes was evaluated using heterologous
      expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and
      by Western blot analysis. The members of the PcNLP family can induce chlorosis or
      necrosis during infection of pepper and tobacco leaves, but the chlorotic or
      necrotic response caused by PcNLP genes was stronger in pepper leaves than in
      tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest
      chlorotic or necrotic areas in both host plants, indicating that these three
      genes contribute to strong virulence during infection by P. capsici. This was
      confirmed through functional evaluation of their silenced transformants. In
      addition, we further verified that four conserved residues are putatively active
      sites in PcNLP1 by site-directed mutagenesis. CONCLUSIONS: Each targeted PcNLP
      gene affects cells or tissues differently depending upon the stage of infection.
      Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in
      the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have
      different phytotoxic effects, and PcNLP2, PcNLP6, and PcNLP14 may play important
      roles in symptom development and may be crucial for virulence, necrosis-inducing
      activity, or cell death during infection by P. capsici.

PMID- 24886311
TI  - Changes in public health preparedness services provided to local health
      departments by regional offices in North Carolina: a comparison of two cross
      sectional studies.
AB  - BACKGROUND: In 2011, seven decentralized Public Health Regional Surveillance
      Teams (PHRSTs) were restructured into four centralized Public Health Preparedness
      and Response (PHP&R) regional offices to realign preparedness priorities and
      essential services with appropriate infrastructure; field-based staff was
      reduced, saving approximately $1 million. The objective of this study was to
      understand the impact that restructuring had on services provided to local health
      departments (LHDs) throughout North Carolina. METHODS: A survey to document
      services that regional offices provide to LHDs in North Carolina was administered
      by the North Carolina Preparedness and Emergency Response Research Center in
      2013. The results were compared to a similar survey from 2009, which identified
      services provided by regional teams prior to restructuring. RESULTS: Of 69 types
      of assistance, 14 (20%) were received by 50% or more LHDs in 2012. Compared to
      2009, there was a significant decrease in the proportion of LHDs receiving 67% (n
      = 47) of services. The size of the region served by regional offices was shown to
      inversely impact the proportion of LHDs receiving services for 25% of services.
      There was a slight significant decline in perceived quality of the services
      provided by regional teams in 2012 as comparison to 2009. CONCLUSIONS: Following
      a system-wide review of preparedness in North Carolina, the state's regional
      teams were reorganized to refine their focus to planning, exercises, and
      training. Some services, most notably under the functions of epidemiology and
      surveillance and public health event response, are now provided by other state
      offices. However, the study results indicate that several services that are still
      under the domain of the regional offices were received by fewer LHDs in 2012 than
      2009. This decrease may be due to the larger number of counties now served by the
      four regional offices.

PMID- 24886312
TI  - Reliability, validity, and effectiveness of center of pressure parameters in
      assessing stabilometric platform in subjects with incomplete spinal cord injury:
      a serial cross-sectional study.
AB  - BACKGROUND: Spinal cord injury (SCI) can damage long tracts, affecting postural
      stability. Impairments in balance have recently been proposed to be highly
      predictive of functional recovery in patients with SCI and thus merit evaluation.
      In addition to common observational clinical scales, more objective evaluation
      methods of balance can be implemented by analyzing center of pressure (COP)
      parameters using stabilometric platforms (SPs). COP analysis has been used in
      various pathologies, but the COP parameters with regard to measurement vary,
      depending on the features of the target population, and have only been assessed
      in healthy subjects. Specifically, concerning subjects with SCI, few studies have
      reported COP parameters, and none has addressed the reliability, validity, or
      responsiveness of this measure. The objective of this serial cross-sectional
      study was to analyze the reliability, validity, and responsiveness of COP
      parameters under various conditions in incomplete SCI subjects to assess balance.
      METHODS: Twenty-three patients with incomplete SCI were examined 111 times for 1
      year. Each session comprised administration of the Berg Balance scale, Tinetti
      scale, and WISCI scale and evaluation of stabilometric platform use. Stabilometry
      was performed under various sensory conditions (OF: open feet; CF: closed feet;
      OE: open eyes; CE: closed eyes), wherein several COP parameters were analyzed (L:
      COP path length; V: mean COP velocity, VAP: anteroposterior COP velocity; VLL:
      laterolateral COP velocity, A: COP ellipse area, SA1: x-axis of COP ellipse area;
      SA2: y-axis of COP ellipse area). The reliability, validity, and responsiveness
      of COP parameters that were associated with visual/support area conditions were
      analyzed. RESULTS: Of the COP parameters, V and arithmetically related measures
      had the highest reliability, validity, and effectiveness scores. Of all test
      conditions, OE-OF was the most valid, whereas CE-OF was the most responsive.
      CONCLUSION: The assessment of balance in SCI subjects can be reliable, valid, and
      effective in acquiring V data, based on OF-OE and OF-CE conditions and heel
      distance values.

PMID- 24886313
TI  - TGF-beta1 induces senescence of bone marrow mesenchymal stem cells via increase
      of mitochondrial ROS production.
AB  - BACKGROUND: Bone marrow derived mesenchymal stem cells (bmMSCs) are multipotent
      cells that can differentiate into diverse cell types, including cardiomyocytes.
      BmMSC-based transplantation is capable of repairing acute and chronic myocardial
      infarction. Prior to the transplantation, MSCs are usually induced in vitro by
      biological reagents and chemicals for directional differentiation. Transforming
      growth factor beta (TGF-beta) is one of the most commonly used biological
      reagents for induction of cardiomyocyte differentiation of bmMSCs. Previous
      studies have shown that TGF-beta induces senescence in several cell types.
      However, whether TGF-beta affects senescence of bmMSCs has not been elucidated.
      The goal of this study was to investigate the effect of TGF-beta1 on senescence
      of bmMSCs and the underlying mechanisms. RESULTS: We found that TGF-beta1
      increased activity of senescence-associated-galactosidase (SA-Gal) and production
      of mitochondrial reactive oxygen species (mtROS) in bmMSCs in a dose-dependent
      manner. TGF-beta1 also significantly decreased expression of superoxide dismutase
      2 (SOD2) and Id1, and increased expression of 4-Hydroxynonenal (4-HNE) subunits
      and p16 in bmMSCs in a dose-dependent manner. Pre-treatment with mtROS inhibitor
      acetyl-L-carnitine (ALCAR, 0.1 mM) significantly inhibited TGF-beta1-induced
      mtROS production and SA-Gal activity. CONCLUSION: TGF-beta1 can induce senescence
      of bmMSCs, which at least partially depends on mtROS production.

PMID- 24886314
TI  - Tuberculosis treatment discontinuation and symptom persistence: an observational
      study of Bihar, India's public care system covering >100,000,000 inhabitants.
AB  - BACKGROUND: The effectiveness of India's TB control programs depend critically on
      patients completing appropriate treatment. Discontinuing treatment prior to
      completion can leave patients infectious and symptomatic. Developing strategies
      to reduce early discontinuation requires characterizing its patterns and their
      link to symptom persistence. METHODS: The 2011 BEST-TB survey (360 clusters, 11
      districts) sampled patients (n = 1007) from Bihar's public healthcare system who
      had initiated treatment >6 months prior to being interviewed, administering
      questionnaires to patients about TB treatment duration and symptoms, prior
      treatment, and sociodemographic characteristics. Multivariate logistic regression
      models estimated the risk of treatment discontinuation for these characteristics.
      Similar models estimated probabilities of symptom persistence to 25 weeks post
      treatment initiation adjusting for the same predictors and treatment duration.
      All models included district fixed effects, robust standard errors, and
      adjustments for the survey sampling design. Treatment default timing and symptom
      persistence relied solely on self-report. RESULTS: 24% of patients discontinued
      treatment prior to 25 weeks. Higher likelihood of discontinuation occurred in
      those who had failed to complete previous TB treatment episodes (aOR: 4.77 [95%
      CI: 1.98-11.53]) and those seeing multiple providers (3.67 per provider [1.94
      6.95]). Symptoms persisted in 42% of patients discontinuing treatment within 5
      weeks versus 28% for completing 25 weeks of treatment. Symptom persistence was
      more likely for those with prior TB treatment (aOR: 5.05 [1.90-13.38]); poorer
      patients (2.94 [1.51-5.72]); and women (1.79 [1.07-2.99]). Predictors for
      treatment discontinuation prior to 16 weeks were similar. CONCLUSIONS: Premature
      TB treatment discontinuation and symptom persistence is particularly high among
      individuals who have failed to complete treatment for a prior episode. Strategies
      to identify and promote treatment completion in this group appear promising.
      Likewise, effective TB regimens of shortened duration currently in trials may
      eventually help to achieve higher treatment completion rates.

PMID- 24886315
TI  - De-implementation of inappropriately tight control (of hypoglycemia) for health:
      protocol with an example of a research grant application.
AB  - BACKGROUND: Implementation of practice change is difficult and large scale
      implementation is particularly difficult. Among the challenges facing the
      healthcare system in general and healthcare organizations is the overuse of low
      value care. Improving medication safety also constitutes an attempt to reduce low
      value or potentially harmful care. Critical issues of overuse of low value
      practices and medication safety intersect in overtreatment of diabetes.
      Specifically, (over)intensive glycemic control increases hypoglycemia risk and
      morbidity without providing meaningful benefit. Our work indicates that among
      patients with diabetes who are at high risk for hypoglycemia, potential
      overtreatment is common. The Choosing Wisely Initiative to reduce low value care
      led by the American Board of Internal Medicine Foundation recommends not to treat
      most persons over 65 years of age with medications to reduce the A1c<7.5%. For
      most physicians this involves a change in practice. We will study the
      implementation of the Veterans Health Administration's Choosing Wisely Initiative
      (which includes hypoglycemic safety as a targeted condition) with three specific
      aims: (1) to assess the overall impact, both intended and unintended, of the
      Choosing Wisely Initiative to reduce overtreatment of diabetes in especially
      vulnerable populations; (2) to assess the impact of commitment to quality,
      teaching intensity, and safety culture on likelihood of overtreatment; and (3) to
      identify configurations of the implementation strategy, provider characteristics
      and organizational level factors that are associated with successful reduction of
      overtreatment rates by comparing high and low performers. Because focus on this
      initiative could have the unintended consequence of paying less attention to poor
      glycemic control (A1c>9%), we will also assess undertreatment. METHODS/DESIGN: We
      will take advantage of a natural experiment and use a Type III Hybrid Design that
      focuses on study of implementation while at the same time observing and gathering
      information on clinical interventions and outcomes. This mixed methods study will
      use longitudinal data and qualitative methods including Qualitative Comparative
      Analyses. DISCUSSION: Our multi-paradigm approach to examining potential
      mechanisms to explain the variation in reduction of rates of overtreatment will
      contribute to a better understanding of implementation of national dissemination
      projects and multi-component interventions in complex systems.

PMID- 24886316
TI  - Tumor suppressor miR-24 restrains gastric cancer progression by downregulating
      RegIV.
AB  - BACKGROUND: microRNAs are small noncoding RNAs that modulate a variety of
      cellular processes by regulating multiple targets, which can promote or inhibit
      the development of malignant behaviors. Accumulating evidence suggests miR-24
      plays important roles in human carcinogenesis. However, its precise biological
      role remains largely elusive. This study examined the role of miR-24 in gastric
      cancer (GC). METHODS: The expression of miR-24 in GC tissues compared with
      matched non-tumor tissues and GC cells was detected by qRT-PCR. Synthetic short
      single or double stranded RNA oligonucleotides and lentiviral vectors were used
      to regulate miR-24 expression in GC cells to investigate its function in vitro
      and in vivo. RESULTS: miR-24 was significantly downregulated in GC tissues
      compared with matched non-tumor tissues and was associated with tumor
      differentiation. Ectopic expression of miR-24 in SGC-7901 GC cells suppressed
      cell proliferation, migration and invasion in vitro as well as tumorigenicity in
      vivo by inducing cell cycle arrest in G0/G1 phase and promoting cell apoptosis.
      Furthermore, we identified RegIV as a target of miR-24 and demonstrated that miR
      24 regulated RegIV expression via binding its 3' untranslated region.
      CONCLUSIONS: miR-24 functions as a novel tumor suppressor in GC and the anti
      oncogenic activity may involve its inhibition of the target gene RegIV. These
      findings suggest the possibility for miR-24 as a therapeutic target in GC.

PMID- 24886317
TI  - The battle of the sexes starts in the oviduct: modulation of oviductal
      transcriptome by X and Y-bearing spermatozoa.
AB  - BACKGROUND: Sex allocation of offspring in mammals is usually considered as a
      matter of chance, being dependent on whether an X- or a Y-chromosome-bearing
      spermatozoon reaches the oocyte first. Here we investigated the alternative
      possibility, namely that the oviducts can recognise X- and Y- spermatozoa, and
      may thus be able to bias the offspring sex ratio. RESULTS: By introducing X- or Y
      sperm populations into the two separate oviducts of single female pigs using
      bilateral laparoscopic insemination we found that the spermatozoa did indeed
      elicit sex-specific transcriptomic responses. Microarray analysis revealed that
      501 were consistently altered (P-value < 0.05) in the oviduct in the presence of
      Y-chromosome-bearing spermatozoa compared to the presence of X-chromosome-bearing
      spermatozoa. From these 501 transcripts, 271 transcripts (54.1%) were down
      regulated and 230 transcripts (45.9%) were up-regulated when the Y- chromosome
      bearing spermatozoa was present in the oviduct. Our data showed that local immune
      responses specific to each sperm type were elicited within the oviduct. In
      addition, either type of spermatozoa elicits sex-specific signal transduction
      signalling by oviductal cells. CONCLUSIONS: Our data suggest that the oviduct
      functions as a biological sensor that screens the spermatozoon, and then responds
      by modifying the oviductal environment. We hypothesize that there might exist a
      gender biasing mechanism controlled by the female.

PMID- 24886319
TI  - Validity of SC-StepRx pedometer-derived moderate and vigorous physical activity
      during treadmill walking and running in a heterogeneous sample of children and
      youth.
AB  - BACKGROUND: The purpose of this study was to determine the validity of the SC
      StepRx pedometer to assess moderate and vigorous physical activity during
      treadmill walking and running in a heterogeneous sample of children and youth
      aged 10-17 years. METHODS: Physical activity intensity assessed via indirect
      calorimetry served as the criterion standard. A convenience sample of 40
      participants (20 boys, 20 girls) wore 6 SC-StepRx pedometers, 2 ActiGraph GT3X
      accelerometers, 2 Actical accelerometers, 1 Walk4Life MVP pedometer and 1 NL-1000
      pedometer while walking/running at speeds approximating 2, 3, 4, 6 and 7 METs.
      Associations between indirect calorimetry and each activity monitor were assessed
      using linear regression analyses in SAS 9.2. RESULTS: Estimates of moderate and
      vigorous physical activity from all monitors were significantly associated with
      the criterion standard of indirect calorimetry. The strongest associations with
      the criterion measure were observed for the SC-StepRx with moderate/vigorous
      thresholds of 110/130 steps*minute(-1), and the NL-1000 (R2 = 0.82, p <0.05). The
      SC-StepRx with moderate/vigorous thresholds of 110/130 steps*minute(-1) also
      exhibited the highest combined sensitivity (92.9%) and specificity (96.5%) for
      correctly identifying a bout of moderate-to-vigorous physical activity.
      CONCLUSIONS: This study demonstrates that the SC-StepRx pedometer is a valid tool
      for the measurement of moderate and vigorous physical activity in children and
      youth.

PMID- 24886320
TI  - Performance of steroid eluting bipolar epicardial leads in pediatric and
      congenital heart disease patients: 15 years of single center experience.
AB  - OBJECTIVE: Cardiac pacing is sometimes required for patients with congenital
      heart disease for various reasons. Because of complex anatomy, repetitive
      previous heart surgery and patient size, epicardial leads are of special
      importance in these patients. Using epicardial leads has been discussed
      controversly regarding pacing performance and lead survival. The aim of this
      study was to review the long-term data on pacing performance as well as lead
      survival of epicardial leads implanted in our center. METHODS: Retrospective
      chart review and review of the literature. RESULTS: 82 consecutive pediatric
      patients or adult patients with congenital heart disease with 158 epicardial
      leads (Medtronic 4968, bipolar, steroid - eluting) were included. We found 1.2%
      pacemaker-related early postoperative complications. The incidence of lead
      dysfunction was 7.5% (12/158) for primary (i.e. directly related to the lead
      itself) lead dysfunction and 3.2% (5/158) of lead abandonment for reasons not
      directly related to the lead itself. Primary lead dysfunction occured after a
      median of 3.83 years. Lead survival at 2, 5 and 10 years was 98.7%, 93% and
      92.4%. There were no infections reported. Stable median measurements for
      impedance (RA/RV/LV of 577/483/610 Ohm), sensing threshold (RA/RV/LV of
      2.0/11.0/10.0 mV) and pacing threshold (RA/RV/LV of 0.75 V at 0.4 ms/1.0 V at
      0.49 ms/1.0 V at 0.45 ms) indicated a good mid- to longterm performance. The only
      risk factor for primary lead dysfunction was young age at implantation.
      CONCLUSION: The use of epicardial leads in pediatric and adult patients with
      congenital heart disease shows good longterm outcomes in terms of pacing
      performance and lead survival. The authors encourage using epicardial leads in
      patients with congenital heart disease based on the patient's individual
      characteristics.

PMID- 24886318
TI  - A national case-crossover analysis of the short-term effect of PM2.5 on
      hospitalizations and mortality in subjects with diabetes and neurological
      disorders.
AB  - BACKGROUND: Diabetes and neurological disorders are a growing burden among the
      elderly, and may also make them more susceptible to particulate air matter with
      aerodynamic diameter less than 2.5 MUg (PM2.5). The same biological responses
      thought to effect cardiovascular disease through air pollution-mediated systemic
      oxidative stress, inflammation and cerebrovascular dysfunction could also be
      relevant for diabetes and neurodegenerative diseases. METHODS: We conducted multi
      site case-crossover analyses of all-cause deaths and of hospitalizations for
      diabetes or neurological disorders among Medicare enrollees (>65 years) during
      the period 1999 to 2010 in 121 US communities. We examined whether 1) short-term
      exposure to PM2.5 increases the risk of hospitalization for diabetes or
      neurological disorders, and 2) the association between short-term exposure to
      PM2.5 and all-cause mortality is modified by having a previous hospitalization of
      diabetes or neurological disorders. RESULTS: We found that short term exposure to
      PM2.5 is significantly associated with an increase in hospitalization risks for
      diabetes (1.14% increase, 95% CI: 0.56, 1.73 for a 10 MUg/m3 increase in the 2
      days average), and for Parkinson's disease (3.23%, 1.08, 5.43); we also found an
      increase in all-cause mortality risks (0.64%, 95% CI: 0.42, 0.85), but we didn't
      find that hospitalization for diabetes and neurodegenerative diseases modifies
      the association between short term exposure to PM2.5 and all-cause mortality.
      CONCLUSION: We found that short-term exposure to fine particles increased the
      risk of hospitalizations for Parkinson's disease and diabetes, and of all-cause
      mortality. While the association between short term exposure to PM2.5 and
      mortality was higher among Medicare enrollees that had a previous admission for
      diabetes and neurological disorders than among Medicare enrollees that did not
      had a prior admission for these diseases, the effect modification was not
      statistically significant. We believe that these results provide useful insights
      regarding the mechanisms by which particles may affect the brain. A better
      understanding of the mechanisms will enable the development of new strategies to
      protect individuals at risk and to reduce detrimental effects of air pollution on
      the nervous system.

PMID- 24886321
TI  - Transfers to metropolitan hospitals and coronary angiography for rural Aboriginal
      and non-Aboriginal patients with acute ischaemic heart disease in Western
      Australia.
AB  - BACKGROUND: Aboriginal people have a disproportionately higher incidence rate of
      ischaemic heart disease (IHD) than non-Aboriginal people. The findings on
      Aboriginal disparity in receiving coronary artery procedures are inconclusive. We
      describe the profile and transfers of IHD patients admitted to rural hospitals as
      emergency admissions and investigate determinants of transfers and coronary
      angiography. METHODS: Person-linked hospital and mortality records were used to
      identify 28-day survivors of IHD events commencing at rural hospitals in Western
      Australia. Outcome measures were receipt of coronary angiography, transfer to a
      metropolitan hospital, and coronary angiography if transferred to a metropolitan
      hospital. RESULTS: Compared to non-Aboriginal patients, Aboriginal patients with
      IHD were more likely to be younger, have more co-morbidities, reside remotely,
      but less likely to have private insurance. After adjusting for demographic
      characteristics, Aboriginal people with MI were less likely to be transferred to
      a metropolitan hospital, and if transferred were less likely to receive coronary
      angiography. These disparities were not significant after adjusting for
      comorbidities and private insurance. In the full multivariate model age,
      comorbidities and private insurance were adversely associated with transfer to a
      metropolitan hospital and coronary angiography. CONCLUSION: Disparity in
      receiving coronary angiography following emergency admission for IHD to rural
      hospitals is mediated through the lower likelihood of being transferred to
      metropolitan hospitals where this procedure is performed. The likelihood of a
      transfer is increased if the patient has private insurance, however, rural
      Aboriginal people have a lower rate of private insurance than their non
      Aboriginal counterparts. Health practitioners and policy makers can continue to
      claim that they treat Aboriginal and non-Aboriginal people alike based upon
      clinical indications, as private insurance is acting as a filter to reduce rural
      residents accessing interventional cardiology. If health practitioners and policy
      makers are truly committed to reducing health disparities, they must reflect upon
      the broader systems in which disparity is perpetuated and work towards a systems
      improvement.

PMID- 24886322
TI  - Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads.
AB  - BACKGROUND: Tumors drive blood vessel growth to obtain oxygen and nutrients to
      support tumor expansion, and they also can induce lymphatic vessel growth to
      facilitate fluid drainage and metastasis. These processes have generally been
      studied separately, so that it is not known how peritumoral blood and lymphatic
      vessels grow relative to each other. METHODS: The murine B16-F10 melanoma and
      chemically-induced squamous cell carcinoma models were employed to analyze large
      red-colored vessels growing between flank tumors and draining lymph nodes.
      Immunostaining and microscopy in combination with dye injection studies were used
      to characterize these vessels. RESULTS: Each peritumoral red-colored vessel was
      found to consist of a triad of collecting lymphatic vessel, vein, and artery,
      that were all enlarged. Peritumoral veins and arteries were both functional, as
      detected by intravenous dye injection. The enlarged lymphatic vessels were
      functional in most mice by subcutaneous dye injection assay, however tumor growth
      sometimes blocked lymph drainage to regional lymph nodes. Large red-colored
      vessels also grew between benign papillomas or invasive squamous cell carcinomas
      and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of
      the red-colored vessels again identified the clustered growth of enlarged
      collecting lymphatics, veins, and arteries in the vicinity of these spontaneously
      arising tumors. CONCLUSIONS: Implanted and spontaneously arising tumors induce
      coordinate growth of blood and lymphatic vessel triads. Many of these vessel
      triads are enlarged over several cm distance between the tumor and regional lymph
      nodes. Lymphatic drainage was sometimes blocked in mice before lymph node
      metastasis was detected, suggesting that an unknown mechanism alters lymph
      drainage patterns before tumors reach draining lymph nodes.

PMID- 24886323
TI  - Interactomics profiling of the negative regulatory function of carbon monoxide on
      RANKL-treated RAW 264.7 cells during osteoclastogenesis.
AB  - BACKGROUND: During osteoclastogenesis, the maturation of osteoclast (OC)
      progenitors is stimulated by the receptor activator of nuclear factor-kappaB
      ligand (RANKL). Excess OC production plays a critical role in the pathogenesis of
      inflammatory bone disorders. Conversely, the inhibition of abnormal OC
      proliferation reduces inflammation-induced bone loss. Low concentrations of
      carbon monoxide (CO) are known to decrease inflammation and OC-mediated bone
      erosion but the molecular mechanism is unknown. RESULTS: To obtain insight into
      the biological function of CO, cultured RANKL-treated RAW 264.7 cells were used
      in an in vitro experimental model of osteoclastogenesis. The results showed that
      CO inhibited: 1) tartrate-resistant acid phosphatase (TRAP)-positive cell
      formation; 2) F-actin ring production; 3) c-fos pathway activation; 4) the
      expression of cathepsin K, TRAP, calcitonin receptor, and matrix
      metalloproteinase-9 mRNAs; 5) the expression of nuclear factor of activated T
      cells, cytoplasmic, calcineurin-dependent 1 in translation. Protein-protein
      interaction analysis predicted mitogen-activated protein kinase kinase kinase 4
      as the controlling hub. CONCLUSIONS: Low-concentrations of CO (250 ppm) may
      inhibit osteoclastogenesis. Data from STRING- and IPA-based interactome analyses
      suggested that the expression of proteins with the functions of signal
      transduction, enzymes, and epigenetic regulation are significantly altered by CO
      during RANKL-induced osteoclastogenesis. Our study provides the first interactome
      analysis of osteoclastogenesis, the results of which supported the negative
      regulation of OC differentiation by CO.

PMID- 24886324
TI  - Meeting physical activity guidelines is associated with reduced risk for
      cardiovascular disease in black South African women; a 5.5-year follow-up study.
AB  - BACKGROUND: Low levels of physical activity (PA) have been associated with
      increased risk for cardiovascular disease (CVD) and type 2 diabetes (T2D), but
      few studies have examined whether meeting international PA guidelines is
      associated with reduced risk in a black South African (SA) population. The aims
      of this study were to compare body composition and cardio-metabolic risk factors
      for CVD and T2D between active and inactive groups (part 1, cross-sectional
      analysis) and, to determine whether PA level predicts changes in body composition
      and cardio-metabolic risk factors for CVD and T2D at follow-up after 5.5-years
      (part 2, longitudinal analysis). METHODS: Part 1 included a sample of 240
      apparently healthy black SA women (26 +/- 7 years) who underwent the following
      measurements at baseline: PA (Global Physical Activity Questionnaire (GPAQ)),
      body composition and regional fat distribution (dual-energy x-ray absorptiometry
      and computerised tomography), blood pressure, fasting glucose, insulin and lipid
      concentrations. For part 2, a sub-sample of women (n = 57) underwent the same
      measurements after a 5.5-year period. RESULTS: At baseline, 61% of women were
      classified as meeting the guidelines for moderate- to vigorous-intensity physical
      activity (MVPA) according to GPAQ. Women who were active had significantly lower
      body weight (p < 0.001), body fat (BMI, fat mass, % body fat, waist
      circumference, central and appendicular fat mass, all p < 0.001), and measures of
      insulin resistance (fasting serum insulin and HOMA-IR, both p = 0.01), and higher
      high-density lipoprotein cholesterol (p = 0.041), compared to the inactive group.
      At follow-up, all body fat measures increased significantly in both groups and
      diastolic blood pressure decreased significantly in those who were active at
      baseline, but did not change in those who were inactive. CONCLUSIONS: Meeting PA
      guidelines was associated with decreased risk for CVD and T2D in black SA women,
      but did not prevent the increase in body fat over time. Interventions promoting
      physical activity to specifically address obesity in this high-risk group are
      recommended.

PMID- 24886325
TI  - Mannose-binding lectin gene variants and infections in patients receiving
      autologous stem cell transplantation.
AB  - BACKGROUND: Serious infections are common in patients undergoing autologous stem
      cell transplantation (ASCT) mainly because of the effects of immunosuppression.
      The innate immune system plays an important role in the defense against different
      infections. Mannose binding lectin (MBL) is a central molecule of the innate
      immune system. There are several promoter polymorphisms and structural variants
      of the MBL2 gene that encodes for this protein. These variants produce low levels
      of MBL and have been associated with an increased risk for infections. METHODS:
      Prospective cohort study. The incidence, severity of infections and mortality in
      72 consecutive patients with hematologic diseases who underwent ASCT between
      February 2006 and June 2008 in a tertiary referral center were analyzed according
      to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and
      genotyping. Relative risks (RR) (IC95%) as measure of association were
      calculated. Multivariate analysis was performed using logistic regression.
      RESULTS: A statistically significant higher number of fungal infections was found
      in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016).
      In this MBL2 variant group infection was more frequently the cause of mortality
      than in the MBL2 wild-type group (p=0.05). Although not statistically
      significant, there was a higher incidence of major infections in the MBL2 variant
      group as well as a higher number of infections caused by gram-positive bacteria.
      CONCLUSIONS: Low-producer MBL2 genotypes were associated with an increased number
      of fungal infections in ASCT patients, which would suggest that MBL has a
      protective role against such infections. ASCT patients with MBL2 variant
      genotypes are more likely to die as a result of an infection.

PMID- 24886327
TI  - 3D cardiac microvessels embolization imaging based on X-ray phase contrast
      imaging.
AB  - BACKGROUND: The treatment of microcirculatory impairment will have great impact
      if it can be applied to myocardial infarction (MI) patients. The problem is how
      to study these tiny structures and microphenomenon in heart. METHODS: We
      investigated the visualization of cardiac microvessels embolization by the mean
      of X-ray phase contrast imaging (XPCI), which is a recently emerged imaging
      technique. Using the information of X-ray phase shift, it is sensitive to weak
      absorbing materials. Two MI SD rats were used as the microvessel embolization
      samples. MI was surgically induced by ligating left anterior descending artery.
      Imaging was performed 24 hours post-infarct, with barium sulfate as contrast
      agent. RESULTS: The coronary arteries were visualized with smooth walls and clear
      edges. The ligated vessels, with the diameter of about three hundred microns, can
      be clearly distinguished and there were no distal blood flow downstream from
      these branches. The results indicate that phase contrast imaging can directly
      demonstrate the distribution of microvessels, and estimate the area of MI. The
      infarct location was in good agreement with pathological analyses of the models.
      CONCLUSIONS: The advantage of our method is directly observing and evaluating
      microvessel embolization which simplifies the procedure of diagnoses. Moreover,
      it is helpful for predicting the prognosis in MI and judging if angiogenesis
      happens.

PMID- 24886328
TI  - Hemispheric differences in the surgical outcomes of patients with traumatic acute
      subdural hematoma.
AB  - BACKGROUND: Our assumption that prognosis of patients with traumatic acute
      subdural hematoma (ASDH) does not differ significantly according to the
      hemispheric laterality has never been verified. METHODS: A review of the
      charts/radiographic images of 61 adult traumatic ASDH patients (33 left/28 right)
      was conducted. Intergroup comparison was made on the demographics,
      autonomic/laboratory data, and outcomes (90-day mortality rate). Based on the
      presence of concomitant brain contusion, patients were further quadrichotomized
      as: left ASDH with contusion (n = 14), right ASDH with contusion (n = 16), left
      ASDH without contusion (n = 19), and right ASDH without contusion (n = 12).
      Comparisons were made on demographic and outcome variables between the left ASDH
      with contusion and right ASDH with contusion, and between the left ASDH without
      contusion and right ASDH without contusion. Multivariate regression analysis was
      conducted to identify clinical variables correlated with fatality. RESULTS: There
      were no significant differences in the demographic, autonomic, and laboratory
      data between the left and right ASDH patients. However, 90-day mortality rate was
      significantly higher in the left ASDH patients when concomitant contusion was
      present (79% vs. 25%, p = 0.009). However, there were no significant hemispheric
      differences in the mortality rate among those without contusion (32% vs. 33%, p =
      0.77). Multivariate regression analysis showed that left ASDH was correlated with
      fatality among those with contusion (OR: 6.620; 95% CI: 1.219-46.249).
      CONCLUSIONS: This study is probably the first to report that the left ASDH
      patients fared substantially worse than the right-sided counterparts. Future
      trials on traumatic ASDHs may benefit from considering hemispheric differences in
      the outcomes.

PMID- 24886326
TI  - What explains health in persons with visual impairment?
AB  - BACKGROUND: Visual impairment is associated with important limitations in
      functioning. The International Classification of Functioning, Disability and
      Health (ICF) adopted by the World Health Organisation (WHO) relies on a globally
      accepted framework for classifying problems in functioning and the influence of
      contextual factors. Its comprehensive perspective, including biological,
      individual and social aspects of health, enables the ICF to describe the whole
      health experience of persons with visual impairment. The objectives of this study
      are (1) to analyze whether the ICF can be used to comprehensively describe the
      problems in functioning of persons with visual impairment and the environmental
      factors that influence their lives and (2) to select the ICF categories that best
      capture self-perceived health of persons with visual impairment. METHODS: Data
      from 105 persons with visual impairment were collected, including socio
      demographic data, vision-related data, the Extended ICF Checklist and the visual
      analogue scale of the EuroQoL-5D, to assess self-perceived health. Descriptive
      statistics and a Group Lasso regression were performed. The main outcome measures
      were functioning defined as impairments in Body functions and Body structures,
      limitations in Activities and restrictions in Participation, influencing
      Environmental factors and self-perceived health. RESULTS: In total, 120 ICF
      categories covering a broad range of Body functions, Body structures, aspects of
      Activities and Participation and Environmental factors were identified. Thirteen
      ICF categories that best capture self-perceived health were selected based on the
      Group Lasso regression. While Activities-and-Participation categories were
      selected most frequently, the greatest impact on self-perceived health was found
      in Body-functions categories. The ICF can be used as a framework to
      comprehensively describe the problems of persons with visual impairment and the
      Environmental factors which influence their lives. CONCLUSIONS: There are plenty
      of ICF categories, Environmental-factors categories in particular, which are
      relevant to persons with visual impairment, but have hardly ever been taken into
      consideration in literature and visual impairment-specific patient-reported
      outcome measures.

PMID- 24886329
TI  - The large-scale investigation of gene expression in Leymus chinensis stigmas
      provides a valuable resource for understanding the mechanisms of poaceae self
      incompatibility.
AB  - BACKGROUND: Many Poaceae species show a gametophytic self-incompatibility (GSI)
      system, which is controlled by at least two independent and multiallelic loci, S
      and Z. Until currently, the gene products for S and Z were unknown. Grass SI
      plant stigmas discriminate between pollen grains that land on its surface and
      support compatible pollen tube growth and penetration into the stigma, whereas
      recognizing incompatible pollen and thus inhibiting pollination behaviors. Leymus
      chinensis (Trin.) Tzvel. (sheepgrass) is a Poaceae SI species. A comprehensive
      analysis of sheepgrass stigma transcriptome may provide valuable information for
      understanding the mechanism of pollen-stigma interactions and grass SI. RESULTS:
      The transcript abundance profiles of mature stigmas, mature ovaries and leaves
      were examined using high-throughput next generation sequencing technology. A
      comparative transcriptomic analysis of these tissues identified 1,025
      specifically or preferentially expressed genes in sheepgrass stigmas. These genes
      contained a significant proportion of genes predicted to function in cell-cell
      communication and signal transduction. We identified 111 putative transcription
      factors (TFs) genes and the most abundant groups were MYB, C2H2, C3H, FAR1, MADS.
      Comparative analysis of the sheepgrass, rice and Arabidopsis stigma-specific or
      preferential datasets showed broad similarities and some differences in the
      proportion of genes in the Gene Ontology (GO) functional categories. Potential SI
      candidate genes identified in other grasses were also detected in the sheepgrass
      stigma-specific or preferential dataset. Quantitative real-time PCR experiments
      validated the expression pattern of stigma preferential genes including
      homologous grass SI candidate genes. CONCLUSIONS: This study represents the first
      large-scale investigation of gene expression in the stigmas of an SI grass
      species. We uncovered many notable genes that are potentially involved in pollen
      stigma interactions and SI mechanisms, including genes encoding receptor-like
      protein kinases (RLK), CBL (calcineurin B-like proteins) interacting protein
      kinases, calcium-dependent protein kinase, expansins, pectinesterase, peroxidases
      and various transcription factors. The availability of a pool of stigma-specific
      or preferential genes for L. chinensis offers an opportunity to elucidate the
      mechanisms of SI in Poaceae.

PMID- 24886331
TI  - Analysis of clinical application of thoracoscopic lobectomy for lung cancer.
AB  - BACKGROUND: VATS has been extensively considered as a standard method of
      pulmonary diagnosis and treatment of benign lung diseases. This study aimed to
      investigate the safety, efficacy, and feasibility of video-assisted thoracoscopic
      surgery (VATS) lobectomy compared with conventional lobectomy via open
      thoracotomy in patients with clinical early stage lung cancer. METHODS: A total
      of 120 patients with lung cancer underwent VATS lobectomy; another 120 patients
      with lung cancer underwent conventional lobectomy. The clinical outcomes from
      these two groups were retrospectively analyzed and compared. RESULTS: The numbers
      of patients who underwent lobectomy in the left upper lobe, left lower lobe,
      right upper lobe, right middle lobe, and right lower lobe were 24, 28, 40, 4, and
      24 in the VATS group and 38, 20, 30, 7, and 25 in the conventional group,
      respectively. No statistical differences were observed between the two groups.
      Likewise, no statistical differences were observed in terms of duration of
      operation, time for postoperative extubation, complications, length of hospital
      stay, and number of dissected lymph nodes (VATS group: left, 5.12 +/- 1.45,
      right, 6.84 +/- 1.33; conventional group: left, 4.96 +/- 1.39 mm, right, 6.91 +/-
      1.27; P >0.05). CONCLUSION: Anatomical lobectomy was successfully completed by
      VATS lobectomy for lung cancer; the standard lymph node dissection was also
      achieved. This procedure also showed advantages in terms of surgical bleeding,
      duration, postoperative complications, indwelling time of chest tube, and short
      term recurrence rate without significant differences from conventional lobectomy.

PMID- 24886332
TI  - School nurses' attitudes and experiences regarding the human papillomavirus
      vaccination programme in Sweden: a population-based survey.
AB  - BACKGROUND: Sweden introduced a school-based human papillomavirus (HPV)
      vaccination programme in 2012, and school nurses are responsible for managing the
      vaccinations. The aim of the present study was to investigate the attitudes and
      experiences of school nurses regarding the school-based HPV vaccination programme
      1 year after its implementation. METHODS: Data were collected using a web-based
      questionnaire in the spring of 2013, and 83.1% (851/1024) of nurses responded.
      RESULTS: There were strong associations between the nurses' education about the
      HPV vaccine and their perceived knowledge about the vaccine and a favourable
      attitude towards vaccination (both p < 0.001). School nurses who received a high
      level of education were more likely to have a positive attitude to HPV
      vaccination compared with nurses with little education about HPV vaccination
      (adjusted odds ratio [OR] = 9.8; 95% confidence interval [CI]: 3.797-25.132).
      Nurses with high perceived knowledge were more likely to have a positive attitude
      compared with those with a low level of perceived knowledge (OR = 2.5; 95% CI:
      1.299-4.955). If financial support from the government was used to fund an
      additional school nurse, nurses were more likely to have a positive attitude than
      if the financial support was not used to cover the extra expenses incurred by the
      HPV vaccination (OR = 2.1; 95% CI: 1.051-4.010). The majority, 648 (76.1%), had
      been contacted by parents with questions about the vaccine, mostly related to
      adverse effects. In addition, 570 (66.9%) stated that they had experienced
      difficulties with the vaccinations, and 337 (59.1%) of these considered the task
      to be time-consuming. CONCLUSIONS: A high level of education and perceived good
      knowledge about HPV are associated with a positive attitude of school nurses to
      the HPV vaccination programme. Thus, nurses require adequate knowledge,
      education, skills and time to address the questions and concerns of parents, as
      well as providing information about HPV. Strategic financial support is required
      because HPV vaccination is a complex and time-consuming task.

PMID- 24886330
TI  - Delays in receiving obstetric care and poor maternal outcomes: results from a
      national multicentre cross-sectional study.
AB  - BACKGROUND: The vast majority of maternal deaths in low-and middle-income
      countries are preventable. Delay in obtaining access to appropriate health care
      is a fairly common problem which can be improved. The objective of this study was
      to explore the association between delay in providing obstetric health care and
      severe maternal morbidity/death. METHODS: This was a multicentre cross-sectional
      study, involving 27 referral obstetric facilities in all Brazilian regions
      between 2009 and 2010. All women admitted to the hospital with a pregnancy
      related cause were screened, searching for potentially life-threatening
      conditions (PLTC), maternal death (MD) and maternal near-miss (MNM) cases,
      according to the WHO criteria. Data on delays were collected by medical chart
      review and interview with the medical staff. The prevalence of the three
      different types of delays was estimated according to the level of care and
      outcome of the complication. For factors associated with any delay, the PR and
      95%CI controlled for cluster design were estimated. RESULTS: A total of 82,144
      live births were screened, with 9,555 PLTC, MNM or MD cases prospectively
      identified. Overall, any type of delay was observed in 53.8% of cases; delay
      related to user factors was observed in 10.2%, 34.6% of delays were related to
      health service accessibility and 25.7% were related to quality of medical care.
      The occurrence of any delay was associated with increasing severity of maternal
      outcome: 52% in PLTC, 68.4% in MNM and 84.1% in MD. CONCLUSIONS: Although this
      was not a population-based study and the results could not be generalized, there
      was a very clear and significant association between frequency of delay and
      severity of outcome, suggesting that timely and proper management are related to
      survival.

PMID- 24886333
TI  - Clonally expanded human airway smooth muscle cells exhibit morphological and
      functional heterogeneity.
AB  - BACKGROUND: Mesenchyme-derived airway cell populations including airway smooth
      muscle (ASM) cells, fibroblasts and myofibroblasts play key roles in the
      pathogenesis of airway inflammation and remodeling. Phenotypic and functional
      characterisation of these cell populations are confounded by their heterogeneity
      in vitro. It is unclear which mechanisms underlie the creation of these different
      sub-populations.The study objectives were to investigate whether ASM cells are
      capable of clonal expansion and if so (i) what proportion possess this capability
      and (ii) do clonal populations exhibit variation in terms of morphology,
      phenotype, proliferation rates and pro-relaxant or pro-contractile signaling
      pathways. METHODS: Early passage human ASM cells were subjected to single-cell
      cloning and their doubling time was recorded. Immunocytochemistry was performed
      to assess localization and levels of markers previously reported to be
      specifically associated with smooth muscle or fibroblasts. Finally functional
      assays were used to reveal differences between clonal populations specifically
      assessing mitogen-induced proliferation and pro-relaxant and pro-contractile
      signaling pathways. RESULTS: Our studies provide evidence that a high proportion
      (58%) of single cells present within early passage human ASM cell cultures have
      the potential to create expanded cell populations. Despite being clonally
      originated, morphological heterogeneity was still evident within these clonal
      populations as assessed by the range in expression of markers associated with
      smooth muscle cells. Functional diversity was observed between clonal populations
      with 10 MUM isoproterenol-induced cyclic AMP responses ranging from 1.4 - 5.4
      fold cf basal and bradykinin-induced inositol phosphate from 1.8 - 5.2 fold cf
      basal. CONCLUSION: In summary we show for the first time that primary human ASM
      cells are capable of clonal expansion and that the resulting clonal populations
      themselves exhibit phenotypic plasticity.

PMID- 24886334
TI  - The effect of the TLR9 ligand CpG-oligodeoxynucleotide on the protective immune
      response to alcelaphine herpesvirus-1-mediated malignant catarrhal fever in
      cattle.
AB  - We wished to determine the effect of of CpG ODN adjuvant on the magnitude and
      duration of protective immunity against alcelaphine herpesvirus-1 (AlHV-1)
      malignant catarrhal fever (MCF), a fatal lymphoproliferative disease of cattle.
      Immunity was associated with a mucosal barrier of virus-neutralising antibody.
      The results showed that CpG ODN included either with emulsigen adjuvant and
      attenuated AlHV-1 (atAlHV-1) or alone with atAlHV-1 did not affect the overall
      protection from clinical disease or duration of immunity achieved using emulsigen
      and atAlHV-1. This is in contrast to other similar studies in cattle with BoHV-1
      or cattle and pigs with various other immunogens. In addition to this, several
      other novel observations were made, not reported previously. Firstly, we were
      able to statistically verify that vaccine protection against MCF was associated
      with virus-neutralising antibodies (nAbs) in nasal secretions but was not
      associated with antibodies in blood plasma, nor with total virus-specific
      antibody (tAb) titres in either nasal secretions or blood plasma. Furthermore,
      CpG ODN alone as adjuvant did not support the generation of virus-neutralising
      antibodies. Secondly, there was a significant boost in tAb in animals with MCF
      comparing titres before and after challenge. This was not seen with protected
      animals. Finally, there was a strong IFN-gamma response in animals with emulsigen
      and atAlHV-1 immunisation, as measured by IFN-gamma secreting PBMC in culture
      (and a lack of IL-4) that was not affected by the inclusion of CpG ODN. This
      suggests that nAbs at the oro-nasal-pharyngeal region are important in protection
      against AlHV-1 MCF.

PMID- 24886337
TI  - Shift of the critical mixing temperature in strong electric fields. Theory and
      experiment.
AB  - We study the shift in the critical temperature T(c) in binary mixtures in strong
      electric fields. In experiments we measure the nonlinear dielectric effect (NDE)
      in a mixture of nitrobenze and n-octane and calculate Piekara's factor. We find
      that the critical anomaly of Piekara's factor is a function of an electric field
      strength. We propose to explain this observation as a result of a downward shift
      of T(c), and this allows us to calculate (?T(c)/?E(2)) = (-22 +/- 10) * 10(-16)
      (K m(2))/V(2). In the theoretical part we amend Landau and Lifshitz's formula and
      show that the downward shift of Tc can be estimated from a simple mean-field
      theory taking into account the linear and quadratic terms in an expansion of the
      constitutive relation epsilon(x) between the electric constant epsilon and
      mixture composition x.

PMID- 24886335
TI  - Antifungal effectiveness of various intracanal medicaments against Candida
      albicans: an ex-vivo study.
AB  - BACKGROUND: To investigate the antifungal activity of propolis, triple antibiotic
      paste (TAP), 2% chlorhexidine gel and calcium hydroxide with propylene glycol on
      Candida albicans-infected root canal dentinal tubules at two different depths
      (200 MUm and 400 MUm) and two time intervals (day 1 and 7). METHODS: A total of
      90 extracted human teeth were sectioned below the cementoenamel junction and the
      apical part of the root to obtain 6 mm of the middle third of the root. The root
      canal was enlarged to an internal diameter of 0.9 mm using Pesso Reamer size no.
      2 (Mani(r), UT, Japan), followed by canal irrigation and autoclaved. The
      specimens were infected for 21 days with C. albicans. Then, the specimens were
      divided into five groups prior to placement of intracanal medicaments. Group 1
      (propolis), Group 2 (triple antibiotic paste), Group 3 (2% chlorhexidine Gel),
      Group 4 (calcium hydroxide with propylene glycol), and Group 5 (sterile saline as
      negative control). At the end of 1 and 7 days, dentine shavings were collected at
      two depths into the dentinal tubules (200 MUm and 400 MUm), and the total numbers
      of colony forming units were calculated for assessing the remaining vital viable
      fungal population. The values were analysed statistically using non-paramatric
      Kruskal-Wallis and Mann-Whitney-U tests to compare the median reduction of
      Candida albicans between all intracanal medicaments. Probability values of P <
      0.05 were set as the reference for statistically significant results. RESULTS:
      The reduction in number of colony forming units was statistically significant in
      all groups compared to the control group (sterile saline), except propolis at day
      1 (400 MUm depth). CONCLUSION: Propolis was less effective than triple antibiotic
      paste, 2% chlorhexidine gel and calcium hydroxide with propylene glycol against
      C. albicans on day 1 at 400 MUm deep inside the dentinal tubules, but equally
      effective after 7 days at both depths.

PMID- 24886336
TI  - High glucose induces Smad activation via the transcriptional coregulator p300 and
      contributes to cardiac fibrosis and hypertrophy.
AB  - BACKGROUND: Despite advances in the treatment of heart failure, mortality remains
      high, particularly in individuals with diabetes. Activated transforming growth
      factor beta (TGF-beta) contributes to the pathogenesis of the fibrotic
      interstitium observed in diabetic cardiomyopathy. We hypothesized that high
      glucose enhances the activity of the transcriptional co-activator p300, leading
      to the activation of TGF-beta via acetylation of Smad2; and that by inhibiting
      p300, TGF-beta activity will be reduced and heart failure prevented in a
      clinically relevant animal model of diabetic cardiomyopathy. METHODS: p300
      activity was assessed in H9c2 cardiomyoblasts under normal glucose (5.6 mmol/L
      NG) and high glucose (25 mmol/L-HG) conditions. 3H-proline incorporation in
      cardiac fibroblasts was also assessed as a marker of collagen synthesis. The role
      of p300 activity in modifying TGF-beta activity was investigated with a known
      p300 inhibitor, curcumin or p300 siRNA in vitro, and the functional effects of
      p300 inhibition were assessed using curcumin in a hemodynamically validated model
      of diabetic cardiomyopathy - the diabetic TG m(Ren-2)27 rat. RESULTS: In vitro,
      H9c2 cells exposed to HG demonstrated increased p300 activity, Smad2 acetylation
      and increased TGF-beta activity as assessed by Smad7 induction (all p < 0.05 c/w
      NG). Furthermore, HG induced 3H-proline incorporation as a marker of collagen
      synthesis (p < 0.05 c/w NG). p300 inhibition, using either siRNA or curcumin
      reduced p300 activity, Smad acetylation and TGF-beta activity (all p < 0.05 c/w
      vehicle or scrambled siRNA). Furthermore, curcumin therapy reduced 3H-proline
      incorporation in HG and TGF-beta stimulated fibroblasts (p < 0.05 c/w NG). To
      determine the functional significance of p300 inhibition, diabetic Ren-2 rats
      were randomized to receive curcumin or vehicle for 6 weeks. Curcumin treatment
      reduced cardiac hypertrophy, improved diastolic function and reduced
      extracellular matrix production, without affecting glycemic control, along with a
      reduction in TGF-beta activity as assessed by Smad7 activation (all p < 0.05 c/w
      vehicle treated diabetic animals). CONCLUSIONS: These findings suggest that high
      glucose increases the activity of the transcriptional co-regulator p300, which
      increases TGF-beta activity via Smad2 acetylation. Modulation of p300 may be a
      novel strategy to treat diabetes induced heart failure.

PMID- 24886338
TI  - Effectiveness of the Epley's maneuver performed in primary care to treat
      posterior canal benign paroxysmal positional vertigo: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Vertigo is a common medical condition with a broad spectrum of
      diagnoses which requires an integrated approach to patients through a structured
      clinical interview and physical examination. The main cause of vertigo in primary
      care is benign paroxysmal positional vertigo (BPPV), which should be confirmed by
      a positive D-H positional test and treated with repositioning maneuvers. The
      objective of this study is to evaluate the effectiveness of Epley's maneuver
      performed by general practitioners (GPs) in the treatment of BPPV.
      METHODS/DESIGN: This study is a randomized clinical trial conducted in the
      primary care setting. The study's scope will include two urban primary care
      centers which provide care for approximately 49,400 patients. All patients
      attending these two primary care centers, who are newly diagnosed with benign
      paroxysmal positional vertigo, will be invited to participate in the study and
      will be randomly assigned either to the treatment group (Epley's maneuver) or to
      the control group (a sham maneuver). Both groups will receive betahistine.
      Outcome variables will be: response to the D-H test, patients' report on presence
      or absence of vertigo during the previous week (dichotomous variable: yes/no),
      intensity of vertigo symptoms on a Likert-type scale in the previous week, total
      score on the Dizziness Handicap Inventory (DHI) and quantity of betahistine
      taken. DISCUSSION: Positive results from our study will highlight that treatment
      of benign paroxysmal positional vertigo can be performed by trained general
      practitioners (GPs) and, therefore, its widespread practice may contribute to
      improve the quality of life of BPPV patients. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01969513.

PMID- 24886339
TI  - Ethical considerations of worksite health promotion: an exploration of
      stakeholders' views.
AB  - BACKGROUND: Developing, implementing and evaluating worksite health promotion
      requires dealing with all stakeholders involved, such as employers, employees,
      occupational physicians, insurance companies, providers, labour unions and
      research and knowledge institutes. Although worksite health promotion is becoming
      more common, empirical research on ethical considerations of worksite health
      promotion is scarce. METHODS: We explored the views of stakeholders involved in
      worksite health promotion in focus group discussions and we described the ethical
      considerations that result from differences between these views. The focus group
      discussions were organised per stakeholder group. Data were analysed according to
      the constant comparison method. RESULTS: Our analyses show that although the
      definition of occupational health is the same for all stakeholders, namely 'being
      able to perform your job', there seem to be important differences in the views on
      what constitutes a risk factor to occupational health. According to the
      employees, risk factors to occupational health are prevailingly job-related.
      Labour unions agree with them, but other stakeholders, including the employer,
      particularly see employee-related issues such as lifestyle behaviour as risk
      factors to occupational health. The difference in definition of occupational
      health risk factors translates into the same categorisation of worksite health
      promotion; employee-related activities and work-related activities. The
      difference in conceptualisation of occupational health risk factors and worksite
      health promotion resonates in the way stakeholders understand 'responsibility'
      for lifestyle behaviour. Even though all stakeholders agree on whose
      responsibility lifestyle behaviour is, namely that of the employee, the meaning
      of 'responsibility' differs between employees, and employers. For employees,
      responsibility means autonomy, while for employers and other stakeholders,
      responsibility equals duty. This difference may in turn contribute to ambivalent
      relationships between stakeholders. CONCLUSION: All stakeholders, including
      employees, should be given a voice in developing, implementing and evaluating
      worksite health promotion. Moreover, since stakeholders agree on lifestyle being
      the responsibility of the employee, but disagree on what this responsibility
      means (duty versus autonomy), it is of utmost importance to examine the discourse
      of stakeholders. This way, ambivalence in relationships between stakeholders
      could be prevented.

PMID- 24886340
TI  - Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic
      syndrome: a predictive marker of risk and drug responsiveness.
AB  - BACKGROUND: Treatment of idiopathic membranous nephropathy with nephrotic
      syndrome is still controversial. There is currently little known about the
      clinical use of renal biomarkers which may explain contradictory results obtained
      from clinical trials. In order to assess whether IgG-uria can predict the outcome
      in membranous nephropathy, we examined the value of baseline EF-IgG in predicting
      remission and progression of nephrotic syndrome. METHODS: In a prospective cohort
      of 84 (34 female) idiopathic membranous nephropathy patients with nephrotic
      syndrome we validated the ability of the clinically available urine biomarker,
      IgG, to predict the risk of kidney disease progression and the beneficial effect
      of immunosuppression with steroids and cyclophosphamide. The fractional excretion
      of IgG (FE-IgG) and alpha1-microglobulin (FE-alpha1m), urine albumin/creatinine
      ratio, and eGFR were measured at the time of kidney biopsy. Primary outcome was
      progression to end stage kidney failure or kidney function (eGFR) decline >= 50%
      of baseline. Patients were followed up for 7.2 +/- 4.1 years (range 1-16.8).
      RESULTS: High FE-IgG (>= 0.02) predicted an increased risk of kidney failure
      (Hazard Ratio, (HR) 8.2, 95%CI 1.0-66.3, p=0.048) and lower chance of remission
      (HR 0.18, 95%CI 0.09-0.38, p<0.001). The ten-year cumulative risk of kidney
      failure was 51.7% for patients with high FE-IgG compared to only 6.2% for
      patients with low FE-IgG. During the study, only 24% of patients with high FE-IgG
      entered remission compared to 90% of patients with low FE-IgG. Combined treatment
      with steroids and cyclophosphamide decreased the progression rate (-40%) and
      increased the remission rate (+36%) only in patients with high FE-IgG.
      CONCLUSION: In idiopathic membranous nephropathy patients with nephrotic
      syndrome, FE-IgG could be useful for predicting kidney disease progression,
      remission, and response to treatment.

PMID- 24886341
TI  - Teaching communication skills in clinical settings: comparing two applications of
      a comprehensive program with standardized and real patients.
AB  - BACKGROUND: Communication is important for the quality of clinical practice, and
      programs have been implemented to improve healthcare providers' communication
      skills. However, the consistency of programs teaching communication skills has
      received little attention, and debate exists about the application of acquired
      skills to real patients. This study inspects whether (1) results from a
      communication program are replicated with different samples, and (2) results with
      standardized patients apply to interviews with real patients. METHODS: A
      structured, nine-month communication program was applied in two consecutive years
      to two different samples of healthcare professionals (25 in the first year, 20 in
      the second year). Results were assessed at four different points in time, each
      year, regarding participants' confidence levels (self-rated), basic communication
      skills in interviews with standardized patients, and basic communication skills
      in interviews with real patients. Data were analyzed using GLM Repeated-Measures
      procedures. RESULTS: Improvements were statistically significant in both years in
      all measures except in simulated patients' assessment of the 2008 group.
      Differences between the two samples were non-significant. Differences between
      interviews with standardized and with real patients were also non-significant.
      CONCLUSIONS: The program's positive outcomes were replicated in different
      samples, and acquired skills were successfully applied to real-patient
      interviews. This reinforces this type of program structure as a valuable training
      tool, with results translating into real situations. It also adds to the
      reliability of the assessment instruments employed, though these may need
      adaptation in the case of real patients.

PMID- 24886342
TI  - Totally implantable venous access devices: retrospective analysis of different
      insertion techniques and predictors of complications in 796 devices implanted in
      a single institution.
AB  - BACKGROUND: The aim of this study was to assess the efficacy and safety of
      totally implanted vascular devices (TIVAD) using different techniques of
      insertion. METHODS: We performed a retrospective study using a prospective
      collected database of 796 consecutive oncological patients in which TIVADs were
      inserted. We focused on early and late complications following different
      insertion techniques (surgical cutdown, blind and ultrasound guided percutaneous)
      according to different techniques. RESULTS: Ultrasound guided technique was used
      in 646 cases, cephalic vein cutdown in 102 patients and percutaneous blind
      technique in 48 patients. The overall complication rate on insertion was 7.2% (57
      of 796 cases). Early complications were less frequent using the ultrasound guided
      technique: arterial puncture (p = 0.009), technical failure (p = 0.009), access
      site change after first attempt (p = 0.002); pneumothorax occurred in 4 cases,
      all using the blind percutaneus technique. Late complications occurred in 49
      cases (6.1%) which required TIVAD removal in 43 cases and included: sepsis (29
      cases), thrombosis (3 cases), dislocation (7 cases), skin dehiscence (3 cases),
      and severe pain (1 case). CONCLUSION: Ultrasound guided technique is the safest
      option for TIVAD insertion, with the lowest rates of immediate complications.

PMID- 24886343
TI  - Prevalence of bruxism in children with episodic migraine--a case-control study
      with polysomnography.
AB  - BACKGROUND: Parents of children with migraine have described a higher prevalence
      of sleep bruxism and other sleep disturbances in their children. The objective of
      this study was to use polysomnography to investigate the prevalence of bruxism
      during sleep in children with episodic migraine relative to controls. FINDINGS:
      Controls and patients were matched by sex, age, years of formal education,
      presence of snoring, arousals per hour, and respiratory events per hour.A total
      of 20 controls, between 6 and 12 years old, with no history of headache,
      recruited from public schools in Sao Paulo between 2009 and 2012, and 20 patients
      with episodic migraine recruited from the Headache Clinic at the Federal
      University of Sao Paulo between 2009 and 2012 underwent polysomnography.No
      intervention was performed before sleep studies.Among migraine patients, 27.5%
      experienced aura prior to migraine onset. The sleep efficiency, sleep latency,
      REM sleep latency, arousals per hour, percentage of sleep stages, and breathing
      events per hour were similar between groups. Five children (25%) with episodic
      migraine exhibited bruxism during the sleep study while this finding was not
      observed in any control (p = 0.045). CONCLUSIONS: Our data demonstrate that
      bruxism during sleep is more prevalent in children with episodic migraine.
      Further prospective studies will help elucidate the underlying shared
      pathogenesis between bruxism and episodic migraine in children.

PMID- 24886345
TI  - Diverticular disease of the colon presenting as pyometra: a case report.
AB  - INTRODUCTION: Pyometra can be caused by various etiologies. We present a rare
      case of diverticular disease of the colon presenting as pyometra. This type of
      presentation can be challenging even for an astute clinician. CASE PRESENTATION:
      A 74-year-old Caucasian woman with a history of pyometra was referred to our
      gynecology clinic as an urgent case. She was obese, diabetic and hypertensive.
      Due to the patient profile and the clinical presentation, clinicians were misled
      toward a diagnosis of possible endometrial cancer. After further investigations,
      she was found to have colouterine fistula secondary to a diverticular abscess of
      the sigmoid colon. CONCLUSIONS: Persistent vaginal discharge due to pyometra can
      be caused by diverticular disease of the colon. Clinicians should be aware of
      this important differential diagnosis.

PMID- 24886344
TI  - An interprofessional nurse-led mental health promotion intervention for older
      home care clients with depressive symptoms.
AB  - BACKGROUND: Depressive symptoms in older home care clients are common but poorly
      recognized and treated, resulting in adverse health outcomes, premature
      institutionalization, and costly use of health services. The objectives of this
      study were to examine the feasibility and acceptability of a new six-month
      interprofessional (IP) nurse-led mental health promotion intervention, and to
      explore its effects on reducing depressive symptoms in older home care clients
      (>= 70 years) using personal support services. METHODS: A prospective one-group
      pre-test/post-test study design was used. The intervention was a six-month
      evidence-based depression care management strategy led by a registered nurse that
      used an IP approach. Of 142 eligible consenting participants, 98 (69%) completed
      the six-month and 87 (61%) completed the one-year follow-up. Outcomes included
      depressive symptoms, anxiety, health-related quality of life (HRQoL), and the
      costs of use of all types of health services at baseline and six-month and one
      year follow-up. An interpretive descriptive design was used to explore clients',
      nurses', and personal support workers' perceptions about the intervention's
      appropriateness, benefits, and barriers and facilitators to implementation.
      RESULTS: Of the 142 participants, 56% had clinically significant depressive
      symptoms, with 38% having moderate to severe symptoms. The intervention was
      feasible and acceptable to older home care clients with depressive symptoms. It
      was effective in reducing depressive symptoms and improving HRQoL at six-month
      follow-up, with small additional improvements six months after the intervention.
      The intervention also reduced anxiety at one year follow-up. Significant
      reductions were observed in the use of hospitalization, ambulance services, and
      emergency room visits over the study period. CONCLUSIONS: Our findings provide
      initial evidence for the feasibility, acceptability, and sustained effects of the
      nurse-led mental health promotion intervention in improving client outcomes,
      reducing use of expensive health services, and improving clinical practice
      behaviours of home care providers. Future research should evaluate its efficacy
      using a randomized clinical trial design, in different settings, with an adequate
      sample of older home care recipients with depressive symptoms. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier: NCT01407926.

PMID- 24886346
TI  - Pulmonary function in patients with Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder
      characterized by progressive motor, cognitive and psychiatric disturbances. Chest
      muscle rigidity, respiratory muscle weakness, difficulty in clearing airway
      secretions and swallowing abnormalities have been described in patients with
      neurodegenerative disorders including HD. However limited information is
      available regarding respiratory function in HD patients. The purpose of this
      study was to investigate pulmonary function of patients with HD in comparison to
      healthy volunteers, and its association with motor severity. METHODS: Pulmonary
      function measures were taken from 18 (11 male, 7 female) manifest HD patients (53
      +/- 10 years), and 18 (10 male, 8 female) healthy volunteers (52 +/- 11 years)
      with similar anthropometric and life-style characteristics to the recruited HD
      patients. Motor severity was quantified by the Unified Huntington's Disease
      Rating Scale-Total Motor Score (UHDRS-TMS). Maximum respiratory pressure was
      measured on 3 separate days with a week interval to assess test-retest
      reliability. RESULTS: The test-retest reliability of maximum inspiratory and
      expiratory pressure measurements was acceptable for both HD patient and control
      groups (ICC >=0.92), but the values over 3 days were more variable in the HD
      group (CV < 11.1%) than in the control group (CV < 7.6%). The HD group showed
      lower respiratory pressure, forced vital capacity, peak expiratory flow and
      maximum voluntary ventilation than the control group (p < 0.05). Forced vital
      capacity, maximum voluntary ventilation and maximum respiratory pressures were
      negatively (r = -0.57; -0.71) correlated with the UHDRS-TMS (p < 0.05).
      CONCLUSION: Pulmonary function is decreased in manifest HD patients, and the
      magnitude of the decrease is associated with motor severity.

PMID- 24886347
TI  - In vitro interaction of lumefantrine and piperaquine by atorvastatin against
      Plasmodium falciparum.
AB  - BACKGROUND: There is an urgent need for the discovery of new anti-malarial drugs
      and combination therapy. A combinatorial approach protects each drug from the
      development of resistance and reduces generally the overall transmission rate of
      malaria. Statins, the inhibitors of 3-hydroxy-3-methylglutaryl-Coenzyme A
      reductase and a family of lipid-lowering drugs, have in vitro anti-malarial
      properties, and more specially atorvastatin. However, atorvastatin has a short
      elimination half-life (14 hours) and an efficient combination of anti-malarial
      drugs must associate a drug with a short elimination half-life and a drug with a
      long elimination half-life. The objective of the present work was to identify new
      potential partners among standard new anti-malarial drugs with long elimination
      half-life, such as lumefantrine, piperaquine, pyronaridine and atovaquone, to
      improve the in vitro activity of atorvastatin against different Plasmodium
      falciparum strains to treat uncomplicated malaria. METHODS: In vitro interaction
      of atorvastatin in combination with lumefantrine, piperaquine, pyronaridine and
      atovaquone was assessed against 13 P. falciparum strains by isotopic test.
      RESULTS: Atorvastatin showed additive effects with pyronaridine, piperaquine and
      lumefantrine. Atorvastatin increased the in vitro activity of lumefantrine and
      piperaquine at concentrations expected in clinical observations. The average IC50
      values of lumefantrine decreased significantly from 31.9 nM to 20.5 nM (a
      decrease of 35.7%) in combination with 1 MUM of atorvastatin. CONCLUSIONS: Even
      though in vitro data indicate that atorvastatin improved the activity of
      lumefantrine and piperaquine, the same may not necessarily be true in vivo.
      Piperaquine, a new drug with long terminal elimination half-life, is currently a
      very promising anti-malarial drug.

PMID- 24886348
TI  - Use acupuncture to relieve perimenopausal syndrome: study protocol of a
      randomized controlled trial.
AB  - BACKGROUND: Whether acupuncture is effective for relieving perimenopausal
      syndrome has been controversial recently. In this article, we report the protocol
      of a randomized controlled trial using acupuncture to treat perimenopausal
      syndrome, aiming to answer this controversy. DESIGN: A multicenter randomized
      controlled trial with two parallel arms is underway in China. Two hundred and six
      women with perimenopausal syndrome will be randomly assigned to a treatment group
      using acupuncture plus auricular acupressure (AA group) and a control group using
      Climen (Bayer Healthcare Company Limited, Guangzhou, China), a 28-day sequential
      hormone replacement therapy, in a 1:1 ratio. Participants in the AA group will
      receive three acupuncture sessions per week in the first 4 weeks and two sessions
      per week in the following 8 weeks, for a total of 28 sessions over 12 weeks.
      Auricular points will be plastered by Semen Vaccariae twice per week for a
      consecutive 12 weeks, with both ears used alternately. The Climen control group
      is prescribed a tablet containing estradiol valerate 2 mg/day for the first 11
      days, and a tablet containing estradiol valerate 2 mg/day plus cyroterone acetate
      1 mg/day for the following 10 days. The total treatment period of the control
      group is three cycles. The post-treatment follow-up period will last 24 weeks.
      The primary outcome is the Menopause Rating Scale (MRS) assessed at baseline and
      4, 12, 16, 24 and 36 weeks after randomization. The secondary outcomes are
      Menopause-Specific Quality of Life, average hot flash score during 24 hours,
      serum estradiol, follicle-stimulating hormone and luteinizing hormone level. The
      first two secondary outcomes are measured at the same point as the MRS. Other
      secondary outcomes are measured at baseline and 12, 24 weeks after randomization.
      DISCUSSION: The results of this trial, which will be available in 2015, will
      clarify whether acupuncture is effective to relieve perimenopausal syndrome.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01933204 (registered 9 August 2013).

PMID- 24886349
TI  - Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT
      syndrome.
AB  - BACKGROUND: SHORT syndrome is a rare autosomal dominant condition whose name is
      the acronym of short stature, hyperextensibility of joints, ocular depression,
      Rieger anomaly and teething delay (MIM 269880). Additionally, the patients
      usually present a low birth weight and height, lipodystrophy, delayed bone age,
      hernias, low body mass index and a progeroid appearance. CASE PRESENTATION: In
      this study, we used whole-exome sequencing approaches in two patients with
      clinical features of SHORT syndrome. We report the finding of a novel mutation in
      PIK3R1 (c.1929_1933delTGGCA; p.Asp643Aspfs*8), as well as a recurrent mutation
      c.1945C > T (p.Arg649Trp) in this gene. CONCLUSIONS: We found a novel frameshift
      mutation in PIK3R1 (c.1929_1933delTGGCA; p.Asp643Aspfs*8) which consists of a
      deletion right before the site of substrate recognition. As a consequence, the
      protein lacks the position that interacts with the phosphotyrosine residue of the
      substrate, resulting in the development of SHORT syndrome.

PMID- 24886350
TI  - Assessment of atropine-sufentanil-atracurium anaesthesia for endotracheal
      intubation: an observational study in very premature infants.
AB  - BACKGROUND: Premedication before neonatal intubation is heterogeneous and
      contentious. The combination of a short acting, rapid onset opioid with a muscle
      relaxant is considered suitable by many experts. The purpose of this study was to
      describe the tolerance and conditions of intubation following anaesthesia with
      atropine, sufentanil and atracurium in very premature infants. METHODS:
      Monocentric, prospective observational study in premature infants born before 32
      weeks of gestational age, hospitalised in the NICU and requiring semi-urgent or
      elective intubation. Intubation conditions, heart rate, pulse oxymetry (SpO2),
      arterial blood pressure and transcutaneous PCO2 (TcPCO2) were collected in real
      time during 30 minutes following the first drug injection. Repeated physiological
      measurements were analysed using mixed linear models. RESULTS: Thirty five
      intubations were performed in 24 infants with a median post conceptional age of
      27.6 weeks and a median weight of 850 g at the time of intubation. The first
      attempt was successful in 74% and was similar for junior (75%) and senior (74%)
      operators. The operator rated conditions as "excellent" or "good" in 94% of
      intubations. A persistent increase in TcPCO2 as compared to baseline was observed
      whereas other vital parameters showed no significant variations 5, 10, 15 and 30
      minutes after the first drug injection. Eighteen (51%) desaturations (SpO2 less
      than or equal to 80% for more than 60 seconds) and 2 (6%) bradycardia (heart rate
      less than 100 bpm for more than 60 seconds) were observed. CONCLUSION: This drug
      combination offers satisfactory success rate for first attempt and intubation
      conditions for the operator without any significant change in heart rate and
      blood pressure for the patient. However it is associated with frequent
      desaturations and a possible persistent hypercapnia. SpO2 and PCO2 can be
      significantly modified during neonatal intubation and should be cautiously
      followed in this high-risk population.

PMID- 24886351
TI  - Transcriptomic evidence for immaturity of the prefrontal cortex in patients with
      schizophrenia.
AB  - BACKGROUND: Schizophrenia, a severe psychiatric disorder, has a lifetime
      prevalence of 1%. The exact mechanisms underlying this disorder remain unknown,
      though theories abound. Recent studies suggest that particular cell types and
      biological processes in the schizophrenic cortex have a pseudo-immature status in
      which the molecular properties partially resemble those in the normal immature
      brain. However, genome-wide gene expression patterns in the brains of patients
      with schizophrenia and those of normal infants have not been directly compared.
      Here, we show that the gene expression patterns in the schizophrenic prefrontal
      cortex (PFC) resemble those in the juvenile PFC. RESULTS: We conducted a gene
      expression meta-analysis in which, using microarray data derived from different
      studies, altered expression patterns in the dorsolateral PFC (DLFC) of patients
      with schizophrenia were compared with those in the DLFC of developing normal
      human brains, revealing a striking similarity. The results were replicated in a
      second DLFC data set and a medial PFC (MFC) data set. We also found that about
      half of the genes representing the transcriptomic immaturity of the schizophrenic
      PFC were developmentally regulated in fast-spiking interneurons, astrocytes, and
      oligodendrocytes. Furthermore, to test whether medications, which often confound
      the results of postmortem analyses, affect on the juvenile-like gene expressions
      in the schizophrenic PFC, we compared the gene expression patterns showing
      transcriptomic immaturity in the schizophrenic PFC with those in the PFC of
      rodents treated with antipsychotic drugs. The results showed no apparent
      similarities between the two conditions, suggesting that the juvenile-like gene
      expression patterns observed in the schizophrenic PFC could not be accounted for
      by medication effects. Moreover, the developing human PFC showed a gene
      expression pattern similar to that of the PFC of naive Schnurri-2 knockout mice,
      an animal model of schizophrenia with good face and construct validity. This
      result also supports the idea that the transcriptomic immaturity of the
      schizophrenic PFC is not due to medication effects. CONCLUSIONS: Collectively,
      our results provide evidence that pseudo-immaturity of the PFC resembling
      juvenile PFC may be an endophenotype of schizophrenia.

PMID- 24886352
TI  - Healthy eating and lifestyle in pregnancy (HELP): a protocol for a cluster
      randomised trial to evaluate the effectiveness of a weight management
      intervention in pregnancy.
AB  - BACKGROUND: Approximately 1 in 5 pregnant women in the United Kingdom are obese.
      In addition to being associated generally with poor health, obesity is known to
      be a contributing factor to pregnancy and birth complications and the retention
      of gestational weight can lead to long term obesity.This paper describes the
      protocol for a cluster randomised trial to evaluate whether a weight management
      intervention for obese pregnant women is effective in reducing women's Body Mass
      Index at 12 months following birth. METHODS/DESIGN: The study is a cluster
      randomised controlled trial involving 20 maternity units across England and
      Wales. The units will be randomised, 10 to the intervention group and 10 to the
      control group. 570 pregnant women aged 18 years or over, with a Body Mass Index
      of +/=30 (kg/m2) and between 12 and 20 weeks gestation will be recruited. Women
      allocated to the control group will receive usual care and two leaflets giving
      advice on diet and physical activity. In addition to their usual care and the
      leaflets, women allocated to the intervention group will be offered to attend a
      weekly 1.5 hour weight management group, which combines expertise from Slimming
      World with clinical advice and supervision from National Health Service midwives,
      until 6 weeks postpartum.Participants will be followed up at 36 weeks gestation
      and at 6 weeks, 6 months and 12 months postpartum. Body Mass Index at 12 months
      postpartum is the primary outcome. Secondary outcomes include pregnancy weight
      gain, quality of life, mental health, waist-hip ratio, child weight centile,
      admission to neonatal unit, diet, physical activity levels, pregnancy and birth
      complications, social support, self-regulation and self-efficacy. A cost
      effectiveness analysis and process evaluation will also be conducted. DISCUSSION:
      This study will evaluate the effectiveness of a theory-based intervention
      developed for obese pregnant women. If successful the intervention will equip
      women with the necessary knowledge and skills to enable them to make healthier
      choices for themselves and their unborn child. TRIAL REGISTRATION: Current
      Controlled Trials: ISRCTN25260464 Date of registration: 16th April 2010.

PMID- 24886353
TI  - A complex multimodal activity intervention to reduce the risk of dementia in mild
      cognitive impairment--ThinkingFit: pilot and feasibility study for a randomized
      controlled trial.
AB  - BACKGROUND: Dementia affects 35 million people worldwide and is currently
      incurable. Many cases may be preventable because regular participation in
      physical, mental and social leisure activities during middle age is associated
      with up to 47% dementia risk reduction. However, the majority of middle-aged
      adults are not active enough. MCI is therefore a clear target for activity
      interventions aimed at reducing dementia risk. An active lifestyle during middle
      age reduces dementia risk but it remains to be determined if increased activity
      reduces dementia risk when MCI is already evident. Before this can be
      investigated conclusively, complex multimodal activity programmes are required
      that (1) combine multiple health promoting activities, (2) engage people with
      MCI, and (3) result in sufficient adherence rates. METHODS: We designed the
      ThinkingFit programme to engage people with MCI in a complex intervention
      comprised of three activity components: physical activity, group-based cognitive
      stimulation (GCST) and individual cognitive stimulation (ICST). Engagement and
      adherence was promoted by applying specific psychological techniques to enhance
      behavioural flexibility in an early pre-phase and during the course of the
      intervention. To pilot the intervention, participants served as their own
      controls during a 6- to 12-week run-in period, which was followed by 12 weeks of
      activity intervention. RESULTS: Out of 212 MCI patients screened, 163 were
      eligible, 70 consented and 67 completed the intervention (mean age 74 years).
      Activity adherence rates were high: physical activity = 71%; GCST = 83%; ICST =
      67%. Significant treatment effects (p < .05) were evident on physical health
      outcomes (decreased BMI and systolic blood pressure, [pre/post values of
      26.3/25.9 kg/m2 and 145/136 mmHg respectively]), fitness (decreased resting and
      recovery heart rate [68/65 bpm and 75/69 bpm]), and cognition (improved working
      memory [5.3/6.3 items]). CONCLUSIONS: We found satisfactory recruitment,
      retention and engagement rates, coupled with significant treatment effects in
      elderly MCI patients. It appears feasible to conduct randomized controlled trials
      of the dementia prevention potential of complex multimodal activity programmes
      like ThinkingFit. TRIAL REGISTRATION: ClinicalTrials.gov registration nr:
      NCT01603862; date: 17/5/2012.

PMID- 24886354
TI  - Overall survival in response to sorafenib versus radiotherapy in unresectable
      hepatocellular carcinoma with major portal vein tumor thrombosis: propensity
      score analysis.
AB  - BACKGROUND: This study investigated the survival benefits of sorafenib vs.
      radiotherapy (RT) in patients with unresectable hepatocellular carcinoma (HCC)
      and portal vein tumor thrombosis (PVTT) in the main trunk or the first branch.
      METHODS: Ninety-seven patients were retrospectively reviewed. Forty patients were
      enrolled by the Kanagawa Liver Study Group and received sorafenib, and 57
      consecutive patients received RT in our hospital. Overall survival was compared
      between the two groups with PVTT by propensity score (PS) analysis. Factors
      associated with survival were evaluated by multivariate analysis. RESULTS: The
      median treatment period with sorafenib was 45 days, while the median total
      radiation dose was 50 Gy. The Child-Pugh class and the level of invasion into
      hepatic large vessels were significantly more advanced in the RT group than in
      the sorafenib group. Median survival did not differ significantly between the
      sorafenib group (4.3 months) and the RT group (5.9 months; P = 0.115). After PS
      matching (n = 28 per group), better survival was noted in the RT group than in
      the sorafenib group (median survival, 10.9 vs. 4.8 months; P = 0.025). A Cox
      model showed that des-gamma-carboxy prothrombin <1000 mAU/mL at enrollment and RT
      were significant independent predictors of survival in the PS model (P = 0.024,
      HR, 0.508; 95% CI, 0.282 to 0.915; and P = 0.007, HR, 0.434; 95% CI, 0.235 to
      0.779; respectively). CONCLUSIONS: RT is a better first-line therapy than
      sorafenib in patients who have advanced unresectable HCC with PVTT.

PMID- 24886355
TI  - The usefulness of DNA derived from third stage larvae in the detection of
      Ashworthius sidemi infection in European bison, by a simple polymerase chain
      reaction.
AB  - BACKGROUND: Ashworthius sidemi, a blood-sucking nematode, is a primary parasite
      of Asiatic cervides, primarily sika deer (Cervus nippon). As A. sidemi infections
      are common in bison, red and roe deer, and gastrointestinal nematodes are often
      exchanged between animals, it is possible that other farm animals such as cows
      and sheep that may use the same pastures can be infected. Hence,
      histopathological changes observed in the walls of the abomasa and duodena of
      infected wildlife caused by a strong parasite presence may become an important
      health problem also for farm animals. METHODS: In the present study, a simple PCR
      test for the detection of A. sidemi infection in European bison based on DNA from
      third stage infective larvae (L3) has been optimized. RESULTS: The species
      specific primers generated a 406 bp fragment, and A. sidemi DNA could be detected
      at concentrations of 0.1 pg/MUl. The specificity of PCR was confirmed by the use
      of the genomic DNA of adult Ostertagia ostertagi, Haemonchus contortus, Cooperia
      oncophora as negative controls. CONCLUSION: It is possible to detect A. sidemi
      infection in European bison using DNA from L3. If this nematode infection is
      transmitted to cows this method may be effective to diagnose invasion in breeding
      animals in vivo.

PMID- 24886356
TI  - Prevention of mental disorders: evidence, challenges and opportunities.
AB  - Modelling studies suggest that less than 30% of the burden of mental disorders
      can be averted, even with optimal care and access to services. This points to the
      need to reduce the incidence of mental disorders, utilising evidence-based
      prevention strategies and policy action. In this cross-journal article collection
      (http://www.biomedcentral.com/series/PMD), the case for prevention is made by
      identifying initiatives with established efficacy, as well as opportunities and
      targets for the prevention of mental disorders in early life, in the workplace
      and at the population level. These articles provide reviews, systematic and
      narrative, outlining the evidence base for prevention approaches, as well as
      comment and debate designed to prompt discussion and a reconsideration of
      strategies for prevention. Barriers to expanding the research into prevention
      include the reluctance of governments and funding bodies to invest in research
      and policy action that may take many years to manifest benefits. The case for the
      cost-effectiveness of preventing mental disorders needs to be strongly argued and
      new cross-disciplinary, intersectoral initiatives and policies developed for the
      prevention of mental disorders across the lifespan. 

PMID- 24886357
TI  - Changes in the selected reproductive health indicators among married women of
      reproductive age in low performing areas of Bangladesh: findings from an
      evaluation study.
AB  - BACKGROUND: Three-year duration Demand-Based Reproductive Commodity Project
      (DBRHCP) was launched in three low performing areas: rural Nabiganj (population
      323,357), Raipur (population 260,983) and urban slum in Dhaka (population
      141,912). OBJECTIVES: Assessing changes in knowledge among married women of
      reproductive age on selected reproductive health issues and to explore their
      service utilization patterns over the project period in selected low performing
      areas of Bangladesh. METHODS: The study adopted a pre- posts design. In the
      project areas, the entire chain of service provision were modified through the
      interventions under the DBRHCP, including training of the providers, enhanced
      behavioral change communication activities, follow-up and counseling, record
      keeping, reporting and monitoring, as well as improvement in logistics and
      supplies. Peer promoters were established as linkages between clients and service
      providers. All households were enlisted. Baseline and end line surveys were done
      using representative simple random sampling method, capturing changes over one
      year intervention period. Descriptive analysis was done using SPSS package,
      version 10. Proportional tests using Stata, version 8 were done to assess changes
      from baseline to end line. RESULTS: The overall contraceptive prevalence was
      markedly different in the three study areas but significantly increased in both
      Dhaka urban slums and Nabiganj. In the rural areas, a higher proportion of the
      women in endline compared to baseline obtained contraceptive methods from the
      public sectors. Irrespective of study sites, significantly higher proportion of
      women received ANC (Antenatal Care) and PNC (Post natal care) in endline compared
      to baseline. In all study sites higher proportions of women were aware of
      maternal complications at endline. Services were obtained from qualified persons
      for reported symptoms of sexually transmitted infections by a higher proportion
      of women at endline compared to baseline. There were improvements in other RH
      indicators, such as use of skilled birth attendants and overall utilization of
      health care facilities by women. CONCLUSIONS: The improvements in several
      important RH indicators in the intervention areas suggest that the interventions
      affected selected outcomes reported in the study. The study findings also suggest
      that investment in the reproductive health sector, particularly in existing
      government programs, improves RH outcomes.

PMID- 24886359
TI  - A Bayesian framework for estimating the incremental value of a diagnostic test in
      the absence of a gold standard.
AB  - BACKGROUND: The absence of a gold standard, i.e., a diagnostic reference standard
      having perfect sensitivity and specificity, is a common problem in clinical
      practice and in diagnostic research studies. There is a need for methods to
      estimate the incremental value of a new, imperfect test in this context. METHODS:
      We use a Bayesian approach to estimate the probability of the unknown disease
      status via a latent class model and extend two commonly-used measures of
      incremental value based on predictive values [difference in the area under the
      ROC curve (AUC) and integrated discrimination improvement (IDI)] to the context
      where no gold standard exists. The methods are illustrated using simulated data
      and applied to the problem of estimating the incremental value of a novel
      interferon-gamma release assay (IGRA) over the tuberculin skin test (TST) for
      latent tuberculosis (TB) screening. We also show how to estimate the incremental
      value of IGRAs when decisions are based on observed test results rather than
      predictive values. RESULTS: We showed that the incremental value is greatest when
      both sensitivity and specificity of the new test are better and that conditional
      dependence between the tests reduces the incremental value. The incremental value
      of the IGRA depends on the sensitivity and specificity of the TST, as well as the
      prevalence of latent TB, and may thus vary in different populations. CONCLUSIONS:
      Even in the absence of a gold standard, incremental value statistics may be
      estimated and can aid decisions about the practical value of a new diagnostic
      test.

PMID- 24886358
TI  - Survivin safeguards chromosome numbers and protects from aneuploidy independently
      from p53.
AB  - BACKGROUND: Survivin, a member of the inhibitor of apoptosis (IAP) gene family,
      has a dual role in mitosis and in apoptosis. It is abundantly expressed in every
      human tumor, compared with normal tissues. During mitosis Survivin assembles with
      the chromosomal passenger complex and regulates chromosomal segregation. Here, we
      aim to explore whether interference with the mitotic function of Survivin is
      linked to p53-mediated G1 cell cycle arrest and affects chromosomal stability.
      METHODS: In this study, we used HCT116, SBC-2, and U87-MG and generated
      corresponding isogenic p53-deficient cells. Retroviral vectors were used to
      stably knockdown Survivin. The resulting phenotype, in particular the mechanisms
      of cell cycle arrest and of initiation of aneuploidy, were investigated by
      Western Blot analysis, confocal laser scan microscopy, proliferation assays,
      spectral karyotyping and RNAi. RESULTS: In all cell lines Survivin-RNAi did not
      induce instant apoptosis but caused polyplodization irrespective of p53 status.
      Strikingly, polyploidization after knockdown of Survivin resulted in merotelic
      kinetochore spindle assemblies, gammaH2AX-foci, and DNA damage response (DDR),
      which was accompanied by a transient p53-mediated G1-arrest. That p53 wild type
      cells specifically arrest due to DNA damage was shown by simultaneous inhibition
      of ATM and DNA-PK, which abolished induction of p21waf/cip. Cytogenetic analysis
      revealed chromosomal aberrations indicative for DNA double strand break repair by
      the mechanism of non-homologous end joining (NHEJ), only in Survivin-depleted
      cells. CONCLUSION: Our findings suggest that Survivin plays an essential role in
      proper amphitelic kinetochore-spindle assembly and that constraining Survivin's
      mitotic function results in polyploidy and aneuploidy which cannot be controlled
      by p53. Therefore, Survivin critically safeguards chromosomal stability
      independently from p53.

PMID- 24886360
TI  - WebChem Viewer: a tool for the easy dissemination of chemical and structural data
      sets.
AB  - BACKGROUND: Sharing sets of chemical data (e.g., chemical properties, docking
      scores, etc.) among collaborators with diverse skill sets is a common task in
      computer-aided drug design and medicinal chemistry. The ability to associate this
      data with images of the relevant molecular structures greatly facilitates
      scientific communication. There is a need for a simple, free, open-source program
      that can automatically export aggregated reports of entire chemical data sets to
      files viewable on any computer, regardless of the operating system and without
      requiring the installation of additional software. RESULTS: We here present a
      program called WebChem Viewer that automatically generates these types of highly
      portable reports. Furthermore, in designing WebChem Viewer we have also created a
      useful online web application for remotely generating molecular structures from
      SMILES strings. We encourage the direct use of this online application as well as
      its incorporation into other software packages. CONCLUSIONS: With these features,
      WebChem Viewer enables interdisciplinary collaborations that require the sharing
      and visualization of small molecule structures and associated sets of
      heterogeneous chemical data. The program is released under the FreeBSD license
      and can be downloaded from http://nbcr.ucsd.edu/WebChemViewer. The associated web
      application (called "Smiley2png 1.0") can be accessed through freely available
      web services provided by the National Biomedical Computation Resource at
      http://nbcr.ucsd.edu.

PMID- 24886361
TI  - Early detection and staging of spontaneous embryo resorption by ultrasound
      biomicroscopy in murine pregnancy.
AB  - BACKGROUND: Embryo resorption is a major problem in human medicine, agricultural
      animal production and in conservation breeding programs. Underlying mechanisms
      have been investigated in the well characterised mouse model. However, post
      mortem studies are limited by the rapid disintegration of embryonic structures. A
      method to reliably identify embryo resorption in alive animals has not been
      established yet. In our study we aim to detect embryos undergoing resorption in
      vivo at the earliest possible stage by ultra-high frequency ultrasound. METHODS:
      In a longitudinal study, we monitored 30 pregnancies of wild type C57BI/6 mice
      using ultra-high frequency ultrasound (30-70 MHz), so called ultrasound
      biomicroscopy (UBM). We compared the sonoembryology of mouse conceptuses under
      spontaneous resorption and neighbouring healthy conceptuses and correlated the
      live ultrasound data with the respective histology. RESULTS: The process of
      embryo resorption comprised of four stages: first, the conceptus exhibited growth
      retardation, second, bradycardia and pericardial edema were observed, third,
      further development ceased and the embryo died, and finally embryo remnants were
      resorbed by maternal immune cells. In early gestation (day 7 and 8), growth
      retardation was characterized by a small embryonic cavity. The embryo and its
      membranes were ill defined or did not develop at all. The echodensity of the
      embryonic fluid increased and within one to two days, the embryo and its cavity
      disappeared and was transformed into echodense tissue surrounded by fluid filled
      caverns. In corresponding histologic preparations, fibrinoid material
      interspersed with maternal granulocytes and lacunae filled with maternal blood
      were observed. In later stages (day 9-11) resorption prone embryos were one day
      behind in their development compared to their normal siblings. The space between
      Reichert's membrane and inner yolk sac membrane was enlarged The growth retarded
      embryos exhibited bradycardia and ultimately cessation of heart beat.
      Corresponding histology showed apoptotic cells in the embryo while the placenta
      was still intact. In the subsequent resorption process first the embryo and then
      its membranes disappeared. CONCLUSIONS: Our results provide a temporal time
      course of embryo resorption. With this method, animals exhibiting embryo
      resorption can be targeted, enabling the investigation of underlying mechanisms
      before the onset of total embryo disintegration.

PMID- 24886362
TI  - Natural course of pontocerebellar hypoplasia type 2A.
AB  - INTRODUCTION: Pontocerebellar hypoplasia Type 2 (PCH2) is a rare autosomal
      recessive condition, defined on MRI by a small cerebellum and ventral pons.
      Clinical features are severe developmental delay, microcephaly and
      dyskinesia.Ninety percent carry a p.A307S mutation in the TSEN54-gene. Our aim
      was to describe the natural course including neurological and developmental
      features and other aspects of care in a homogeneous group of PCH2 patients all
      carrying the p.A307S mutation. PATIENTS AND METHODS: Patients were recruited via
      the German patients' organizations. Inclusion criteria were imaging findings of
      PCH2 and a p.A307S mutation. Data were collected using medical reports and
      patient questionnaires discussed in a standardized telephone interview. RESULTS:
      Thirty-three patients were included. When considering survival until age 11
      years, 53% of children had died Weight, length and head circumference, mostly in
      the normal range at birth, became abnormal, especially head circumference (-5.58
      SD at age 5 yrs). Neurologic symptoms: Choreathetosis was present in 88% (62%
      with pyramidal signs), 12% had pure spasticity. Epileptic seizures were manifest
      in 82%, status epilepticus in 39%. Non-epileptic dystonic attacks occurred in
      33%. General symptoms: feeding difficulties were recorded in 100%, sleep disorder
      in 96%, apneas in 67% and recurrent infections in 52%; gastroesophageal reflux
      disease was diagnosed in 73%, 67% got percutaneous endoscopic gastrostomy and 36%
      a Nissen-fundoplication. Neurodevelopmental data: All children made progress, but
      on a low level: such as fixing and following with the eyes was seen in 76%,
      attempting to grasp objects (76%), moderate head control (73%), social smile
      (70%), rolling from prone to supine (58%), and sitting without support (9%). Ten
      percent lost achieved abilities on follow-up. The presence of prenatal symptoms
      did not correlate with outcome. CONCLUSION: Phenotype of this genetically
      homogeneous group of PCH2 children was severe with reduced survival, but
      compatible with some developmental progress. Our data support the hypothesis of
      an early onset degeneration which thereafter stabilizes.

PMID- 24886363
TI  - Hyperuricaemia: a marker of increased cardiovascular risk in rheumatic patients:
      analysis of the ACT-CVD cohort.
AB  - BACKGROUND: Gout and hyperuricaemia may be associated with increased
      cardiovascular risk, but analyses in different populations show conflicting
      results. This study investigates the impact of serum uric acid, inflammation and
      traditional CV risk parameters on CV event risk in patients with gouty arthritis
      and patients with non-gouty rheumatic disease. METHODS: cross-sectional and
      prospective multivariate analysis of the relation between tertiles of serum uric
      acid and individual traditional CV risk factors in a cohort of gouty arthritis
      (GA, n=172), rheumatoid arthritis (RA, n=480) and osteoarthritis (OA, n=206)
      patients. MAIN OUTCOME MEASURES: systolic blood pressure, TC/HDL ratio, GlyHb,
      BMI and first CV events. RESULTS: Individual CV risk factors were significantly
      less favourable in GA (systolic blood pressure, TC/HDL ratio, BMI, p<0.05). In RA
      and OA, but not in GA, individual cardiometabolic parameters correlated with
      serum uric acid values (OA: RA: systolic blood pressure, TC/HDL ratio, BMI;
      systolic blood pressure, TC/HDL ratio, GlyHb, BMI; p<0.05). In non-GA individuals
      the highest tertile of serum uric acid (>0.34 mmol/L) and NT proBNP level were
      independent predictors of first CV events, against age and GlyHb level in GA
      (p<0.05). The hazard of first CV events was equally significantly increased in GA
      patients (HR 3.169, 95% CI 1.287-7.806) and non-GA individuals with a serum uric
      acid >= 0.34 mmol/L (HR 3.721, 95% CI 1.603-8.634) compared to non-GA individuals
      with a serum uric acid < 0.27. CONCLUSIONS: GA is associated with a 3.1-fold
      hazard of first CV events. In non-GA rheumatic patients increasing serum uric
      acid is associated with increased CV risk, whereas CV risk in GA is independent
      of serum uric acid values. The presence of GA or a baseline serum uric acid in
      the upper range are possibly stronger predictors of first CV events than some
      traditional CV risk factors or parameters of inflammation.

PMID- 24886364
TI  - Computed tomographic imaging characteristics of the normal canine lacrimal
      glands.
AB  - BACKGROUND: The canine lacrimal gland (LG) and accessory lacrimal gland of the
      third eyelid (TEG) are responsible for production of the aqueous portion of the
      precorneal tear film. Immune-mediated, toxic, neoplastic, or infectious processes
      can affect the glands directly or can involve adjacent tissues, with secondary
      gland involvement. Disease affecting these glands can cause keratoconjunctivitis
      sicca, corneal ulcers, and loss of vision. Due to their location in the orbit,
      these small structures are difficult to evaluate and measure, making cross
      sectional imaging an important diagnostic tool. The detailed cross-sectional
      imaging appearance of the LG and TEG in dogs using computed tomography (CT) has
      not been reported to date. RESULTS: Forty-two dogs were imaged, and the length,
      width, and height were measured and the volume calculated for the LGs & TEGs. The
      glands were best visualized in contrast-enhanced CT images. The mean volume of
      the LG was 0.14 cm3 and the TEG was 0.1 cm3. The mean height, width, and length
      of the LG were, 9.36 mm, 4.29 mm, and 9.35 mm, respectively; the corresponding
      values for the TEG was 2.02 mm, 9.34 mm, and 7.90 mm. LG and TEG volume were
      positively correlated with body weight (p < 0.05). CONCLUSIONS: Contrast-enhanced
      CT is a valuable tool for noninvasive assessment of canine lacrimal glands.

PMID- 24886365
TI  - AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth
      factor receptor (EGFR), HER2, and HER3: preclinical activity in HER2 non
      amplified inflammatory breast cancer models.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) overexpression has been
      associated with prognostic and predictive value in inflammatory breast cancer
      (IBC). Epidermal growth factor receptor 2 (HER2) overexpression is observed at a
      higher rate in IBC compared with noninflammatory breast cancer. Current
      clinically available anti-HER2 therapies are effective only in patients with HER2
      amplified breast cancer, including IBC. AZD8931 is a novel small-molecule
      equipotent inhibitor of EGFR, HER2, and HER3 signaling. In this study, we
      investigated the antitumor activity of AZD8931 alone or in combination with
      paclitaxel using preclinical models of EGFR-overexpressed and HER2 non-amplified
      IBC cells. METHODS: Two IBC cell lines SUM149 and FC-IBC-02 derived from pleural
      effusion of an IBC patient were used in this study. Cell growth and apoptotic
      cell death were examined in vitro. For the in vivo tumor growth studies, IBC
      cells were orthotopically transplanted into the mammary fat pads of
      immunodeficient mice. AZD8931 was given by daily oral gavage at doses of 25
      mg/kg, 5 days/week for 4 weeks. Paclitaxel was subcutaneously injected twice
      weekly. RESULTS: AZD8931 significantly suppressed cell growth of IBC cells and
      induced apoptosis of human IBC cells in vitro. Significantly, we showed that
      AZD8931 monotherapy inhibited xenograft growth and the combination of paclitaxel
      + AZD8931 was demonstrably more effective than paclitaxel or AZD8931 alone
      treatment at delaying tumor growth in vivo in orthotopic IBC models. CONCLUSION:
      AZD8931 single agent and in combination with paclitaxel demonstrated signal
      inhibition and antitumor activity in EGFR-overexpressed and HER2 non-amplified
      IBC models. These results suggest that AZD8931 may provide a novel therapeutic
      strategy for the treatment of IBC patients with HER2 non-amplified tumors.

PMID- 24886367
TI  - Modular health services: a single case study approach to the applicability of
      modularity to residential mental healthcare.
AB  - BACKGROUND: The Dutch mental healthcare sector has to decrease costs by reducing
      intramural capacity with one third by 2020 and treating more patients in
      outpatient care. This transition necessitates enabling patients to become as self
      supporting as possible, by customising the residential care they receive to their
      needs for self-development. Theoretically, modularity might help mental
      healthcare institutions with this. Modularity entails the decomposition of a
      healthcare service in parts that can be mixed-and-matched in a variety of ways,
      and combined form a functional whole. It brings about easier and better
      configuration, increased transparency and more variety without increasing costs.
      AIM: this study aims to explore the applicability of the modularity concept to
      the residential care provided in Assisted Living Facilities (ALFs) of Dutch
      mental healthcare institutions. METHODS: A single case study is carried out at
      the centre for psychosis in Etten-Leur, part of the GGz Breburg IMPACT care
      group. The design enables in-depth analysis of a case in a specific context. This
      is considered appropriate since theory concerning healthcare modularity is in an
      early stage of development. The present study can be considered a pilot case.
      Data were gathered by means of interviews, observations and documentary analysis.
      RESULTS: At the centre for psychosis, the majority of the residential care can be
      decomposed in modules, which can be grouped in service bundles and sub-bundles;
      the service customisation process is sufficiently fit to apply modular thinking;
      and interfaces for most of the categories are present. Hence, the prerequisites
      for modular residential care offerings are already largely fulfilled. For not yet
      fulfilled aspects of these prerequisites, remedies are available. CONCLUSION: The
      modularity concept seems applicable to the residential care offered by the ALF of
      the mental healthcare institution under study. For a successful implementation of
      modularity however, some steps should be taken by the ALF, such as developing a
      catalogue of modules and a method for the personnel to work with this catalogue
      in application of the modules. Whether implementation of modular residential care
      might facilitate the transition from intramural residential care to outpatient
      care should be the subject of future research.

PMID- 24886366
TI  - The Nakuru eye disease cohort study: methodology & rationale.
AB  - BACKGROUND: No longitudinal data from population-based studies of eye disease in
      sub-Saharan-Africa are available. A population-based survey was undertaken in
      2007/08 to estimate the prevalence and determinants of blindness and low vision
      in Nakuru district, Kenya. This survey formed the baseline to a six-year
      prospective cohort study to estimate the incidence and progression of eye disease
      in this population. METHODS/DESIGN: A nationally representative sample of persons
      aged 50 years and above were selected between January 2007 and November 2008
      through probability proportionate to size sampling of clusters, with sampling of
      individuals within clusters through compact segment sampling. Selected
      participants underwent detailed ophthalmic examinations which included: visual
      acuity, autorefraction, visual fields, slit lamp assessment of the anterior and
      posterior segments, lens grading and fundus photography. In addition,
      anthropometric measures were taken and risk factors were assessed through
      structured interviews. Six years later (2013/2014) all subjects were invited for
      follow-up assessment, repeating the baseline examination methodology. DISCUSSION:
      The methodology will provide estimates of the progression of eye diseases and
      incidence of blindness, visual impairment, and eye diseases in an adult Kenyan
      population.

PMID- 24886368
TI  - Wound healing and antibacterial properties of methanolic extract of Pupalia
      lappacea Juss in rats.
AB  - BACKGROUND: Wound healing is a natural process that enables tissue repair after
      an injury. To shorten its duration and minimize associated complications, wounds
      are treated with medications. Currently there is a growing interest in the use of
      alternative wound dressing agents such as plant extracts. One plant used
      traditionally in wound treatment is Pupalia lappacea. In view of its use in wound
      care, we investigated the wound healing activities of 80% methanolic leave
      extract of Pupalia lappacea using excision, incision and dead space wound models.
      Also its effects on three common wound contaminants were investigated. METHODS:
      Excision wounds were created, contaminated with microbes and treated with
      ointments (10% and 20% w/w) prepared from Pupalia lappacea. Incision and dead
      space wounds were also created in rats which were subsequently dosed orally with
      the extract. The wound healing activities of Pupalia lappacea ointment on
      excision wound was assessed by rates of wound contraction and epithelialization
      as well as its antibacterial effects. The effects of Pupalia lappacea on incision
      and dead-space wounds were determined by the wound breaking strengths and weights
      of the granuloma tissues formed, respectively. RESULTS: Pupalia. lappacea
      ointments significantly (p<0.05) accelerated wound healing with 20% ointment
      having the highest percentage wound contraction and rate of epithelialization. At
      4, 7 and 14 days post treatment, mean total viable bacterial count of excision
      wounds of the extract treated groups were significantly (p<0.05) lower compared
      against the control. Wound breaking strengths and weights of granuloma tissues
      formed in the extract treated groups were significantly (p<0.05) higher than
      those of the control group. The minimum inhibitory concentration values obtained
      for the Pupalia lappacea extract against Pseudomonas aeruginosa, Staphylococcus
      aureus and Bacillus subtilis were 9 mg/ml, 4 mg/ml and 3 mg/ml, respectively,
      while the corresponding minimum bactericidal concentrations were 10 mg/ml, 8
      mg/ml and 7 mg/ml. CONCLUSION: The results obtained showed that Pupalia. lappacea
      has good wound healing and antibacterial activities. These findings validate the
      use of this plant in traditional medicine for treatment of wounds.

PMID- 24886370
TI  - Ciruvis: a web-based tool for rule networks and interaction detection using rule
      based classifiers.
AB  - BACKGROUND: The use of classification algorithms is becoming increasingly
      important for the field of computational biology. However, not only the quality
      of the classification, but also its biological interpretation is important. This
      interpretation may be eased if interacting elements can be identified and
      visualized, something that requires appropriate tools and methods. RESULTS: We
      developed a new approach to detecting interactions in complex systems based on
      classification. Using rule-based classifiers, we previously proposed a rule
      network visualization strategy that may be applied as a heuristic for finding
      interactions. We now complement this work with Ciruvis, a web-based tool for the
      construction of rule networks from classifiers made of IF-THEN rules. Simulated
      and biological data served as an illustration of how the tool may be used to
      visualize and interpret classifiers. Furthermore, we used the rule networks to
      identify feature interactions, compared them to alternative methods, and
      computationally validated the findings. CONCLUSIONS: Rule networks enable a fast
      method for model visualization and provide an exploratory heuristic to
      interaction detection. The tool is made freely available on the web and may thus
      be used to aid and improve rule-based classification.

PMID- 24886369
TI  - In vitro synergism of fosfomycin and clarithromycin antimicrobials against
      methicillin-resistant Staphylococcus pseudintermedius.
AB  - BACKGROUND: Bacterial biofilms are of tremendous concern for clinicians, as they
      can compromise the ability of the immune system and antimicrobial therapy to
      resolve chronic and recurrent infections. Novel antimicrobial therapies or
      combinations targeted against biofilm establishment and growth subsequently
      represent a promising new option for the treatment of chronic infectious
      diseases. In this study, we treated bacterial biofilms produced by methicillin
      resistant Staphylococcus pseudintermedius (MRSP) with a combination of fosfomycin
      and clarithromycin. We selected these agents, because they prevent biofilm
      formation and induce antimicrobial synergism that may also target other
      staphylococci. RESULTS: We determined that the combination of fosfomycin and
      clarithromycin better impairs S. pseudintermedius biofilm formation compared to
      treatment with either therapy alone (P < 0.05). Morphological examination of
      these biofilms via scanning electron microscopy demonstrated that fosfomycin
      alone does impact biofilm formation on orthopaedic implants. However, this
      activity is enhanced in the presence of clarithromycin. We propose that the
      bacteriostatic activity of clarithromycin is accentuated when fosfoymcin is
      present, as it may allow better penetration into the biofilm matrix, allowing
      fosfomycin access to sessile bacteria near the surface of attachment.
      CONCLUSIONS: Here, we demonstrate that the combination of fosfomycin and
      clarithromycin may be a useful therapy that could improve the clinical outcomes
      of treating antimicrobial resistant MRSP biofilms.

PMID- 24886371
TI  - A novel method for studying the temporal relationship between type 2 diabetes
      mellitus and cancer using the electronic medical record.
AB  - BACKGROUND: We developed an algorithm for the identification of patients with
      type 2 diabetes and ascertainment of the date of diabetes onset for examination
      of the temporal relationship between diabetes and cancer using data in the
      electronic medical record (EMR). METHODS: The Marshfield Clinic EMR was searched
      for patients who developed type 2 diabetes between January 1, 1995 and December
      31, 2009 using a combination of diagnostic codes and laboratory data. Subjects
      without diabetes were also identified and matched to subjects with diabetes by
      age, gender, smoking history, residence, and date of diabetes onset/reference
      date. RESULTS: The final cohort consisted of 11,236 subjects with and 54,365
      subjects without diabetes. Stringent requirements for laboratory values resulted
      in a decrease in the number of potential subjects by nearly 70%. Mean observation
      time in the EMR was similar for both groups with 13-14 years before and 5-7 years
      after the reference date. The two cohorts were largely similar except that BMI
      and frequency of healthcare encounters were greater in subjects with diabetes.
      CONCLUSION: The cohort described here will be useful for the examination of the
      temporal relationship between diabetes and cancer and is unique in that it allows
      for determination of the date of diabetes onset with reasonable accuracy.

PMID- 24886372
TI  - Integrating microRNA and mRNA expression profiles in response to radiation
      induced injury in rat lung.
AB  - PURPOSE: Exposure to radiation provokes cellular responses, which are likely
      regulated by gene expression networks. MicroRNAs are small non-coding RNAs, which
      regulate gene expression by promoting mRNA degradation or inhibiting protein
      translation. The expression patterns of both mRNA and miRNA during the radiation
      induced lung injury (RILI) remain less characterized and the role of miRNAs in
      the regulation of this process has not been studied. The present study sought to
      evaluate miRNA and mRNA expression profiles in the rat lung after irradiation.
      METHODS AND MATERIALS: Male Wistar rats were subjected to single dose irradiation
      with 20 Gy using 6 MV x-rays to the right lung. (A dose rate of 5 Gy/min was
      applied). Rats were sacrificed at 3, 12 and 26 weeks after irradiation, and
      morphological changes in the lung were examined by haematoxylin and eosin. The
      miRNA and mRNA expression profiles were evaluated by microarrays and followed by
      quantitative RT-PCR analysis. RESULTS: A cDNA microarray analysis found 2183
      transcripts being up-regulated and 2917 transcripts down-regulated (P <= 0.05,
      >=2.0 fold change) in the lung tissues after irradiation. Likewise, a miRNAs
      microarray analysis indicated 15 miRNA species being up-regulated and 8 down
      regulated (P <= 0.05). Subsequent bioinformatics analyses of the differentially
      expressed mRNA and miRNAs revealed that alterations in mRNA expression following
      irradiation were negatively correlated with miRNAs expression. CONCLUSIONS: Our
      results provide evidence indicating that irradiation induces alterations of mRNA
      and miRNA expression in rat lung and that there is a negative correlation of mRNA
      and miRNA expression levels after irradiation. These findings significantly
      advance our understanding of the regulatory mechanisms underlying the
      pathophysiology of radiation-induced lung injury. In summary, RILI does not
      develop gradually in a linear process. In fact, different cell types interact via
      cytokines in a very complex network. Furthermore, this study suggests that
      microRNAs may serve an important role in the pathogenesis of RILI and that
      understanding their role in RILI may have a significant effect on patient
      management and diagnosis in the future.

PMID- 24886373
TI  - Migraine without aura is not associated with incomplete circle of Willis: a case
      control study using high-resolution magnetic resonance angiography.
AB  - BACKGROUND: The circle of Willis is an important source of collateral blood flow
      to maintain adequate cerebral perfusion, particularly in the posterior
      circulation. Some studies report a relationship between incomplete circle of
      Willis and migraine, whereas other studies show no difference between the
      prevalence of incomplete circle of Willis in migraineurs and controls. In the
      present study we compared the prevalence of incomplete circle of Willis in female
      migraine patients without aura to female healthy non-migraine controls.Using 3
      Tesla magnetic resonance angiography we recorded three-dimensional time-of-flight
      angiograms in 85 female participants (48 migraine patients without aura [median
      age 28 years] and 37 healthy controls [median age 25 years]). The images were
      subsequently analysed blindly by a neuroradiologist to detect incomplete circle
      of Willis. FINDINGS: We found no difference between the prevalence of incomplete
      circle of Willis in patients, 20/47 (43%), and controls, 15/37 (41%), p = 0.252.
      Post hoc analysis showed a significant relationship between age and prevalence of
      incomplete circle of Willis, p = 0.003. CONCLUSION: We found no relationship
      between migraine without aura and incomplete circle of Willis.

PMID- 24886374
TI  - Intimate partner sexual aggression against Chinese women: a mixed methods study.
AB  - BACKGROUND: Although intimate partner sexual aggression has been shown to be
      associated with adverse mental health outcomes, there is scant information about
      sexual aggression in Chinese intimate relationships in general and about its
      mental health impact in particular. This article aimed to investigate sexual
      aggression in Chinese intimate relationships, including the use of force or
      threat of force and non-physical coercive tactics in unwanted sex. METHODS: The
      quantitative and qualitative data used in this paper were drawn from a
      prospective cohort study conducted in Hong Kong between September 2010 and
      September 2012. A total of 745 Chinese women aged 18 or older who had been in an
      intimate relationship in the preceding 12 months were recruited from sites in all
      districts of Hong Kong. Multiple logistic regression analysis, ordinary linear
      regression, and t-tests were used in quantitative analysis. Directed content
      analysis was used to analyze the transcripts of 59 women who revealed experiences
      of intimate partner sexual aggression in individual in-depth interviews. RESULTS:
      Of the 745 Chinese women in the study, 348 (46.7%) had experienced intimate
      partner physical violence in the past year, and 179 (24%) had experienced
      intimate partner physical violence and sexual aggression in the past year.
      Intimate partner sexual aggression significantly predicted PTSD and depressive
      symptoms after controlling for intimate partner physical violence. Among the 179
      women reporting intimate partner physical violence and sexual coercion in the
      past year, 75 indicated that their partners used force or threat of force to make
      them have sex, and 104 of them reported that they gave in to sex because of non
      physical coercive tactics used by their partners. Qualitative data revealed a
      variety of non-physical coercive tactics with different degrees of subtlety used
      to coerce women into unwanted sex with their partners. Chinese women experiencing
      physically forced sex had significantly more depressive symptoms and PTSD
      symptoms. CONCLUSIONS: Our findings indicate that sexual aggression in Chinese
      intimate relationships has specific mental health consequences over and above
      those associated with physical violence. Assessment of partner violence in
      Chinese relationships should include screening for sexual aggression in order to
      provide appropriate interventions. TRIAL REGISTRATION: ClinicalTrials gov
      NCT01206192.

PMID- 24886375
TI  - Utilization of institutional delivery service at Wukro and Butajera districts in
      the Northern and South Central Ethiopia.
AB  - BACKGROUND: Ethiopia has one of the highest maternal mortality in the world.
      Institutional delivery is the key intervention in reducing maternal mortality and
      complications. However, the uptake of the service has remained low and the
      factors which contribute to this low uptake appear to vary widely. Our study aims
      to determine the magnitude and identify factors affecting delivery at health
      institution in two districts in Ethiopia. METHODS: A community based cross
      sectional household survey was conducted from January to February 2012 in 12
      randomly selected villages of Wukro and Butajera districts in the northern and
      south central parts of Ethiopia, respectively. Data were collected using a
      pretested questionnaire from 4949 women who delivered in the two years preceding
      the survey. RESULTS: One in four women delivered the index child at a health
      facility. Among women who delivered at health facility, 16.1% deliveries were in
      government hospitals and 7.8% were in health centers. The factors that
      significantly affected institutional delivery in this study were district in
      which the women lived (AOR: 2.21, 95% CI: 1.28, 3.82), women age at interview
      (AOR: 1.96, 95% CI: 1.05, 3.62), women's education (AOR: 3.53, 95% CI: 1.22,
      10.20), wealth status (AOR: 16.82, 95% CI: 7.96, 35.54), women's occupation (AOR:
      1.50, 95% CI: 1.01, 2.24), antenatal care (4+) use (AOR: 1.77, 95% CI: 1.42,
      2.20), and number of pregnancies (AOR: 0.25, 95% CI: 0.18,0.35). We found that
      women who were autonomous in decision making about place of delivery were less
      likely to deliver in health facility (AOR: 0.38, 95% CI: 0.23,0.63). CONCLUSIONS:
      Institutional delivery is still low in the Ethiopia. The most important factors
      that determine use of institutional delivery appear to be women education and
      household economic status.Women's autonomy in decision making on place of
      delivery did not improve health facility delivery in our study population.Actions
      targeting the disadvantaged, improving quality of services and service
      availability in the area are likely to significantly increase institutional
      delivery.

PMID- 24886376
TI  - Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in
      intraperitoneal implant in mice.
AB  - BACKGROUND: Chronic inflammatory processes in the peritoneal cavity develop as a
      result of ischemia, foreign body reaction, and trauma. Brazilian green propolis,
      a beeswax product, has been shown to exhibit multiple actions on inflammation and
      tissue repair. Our aim was to investigate the effects of this natural product on
      the inflammatory, angiogenic, and fibrogenic components of the peritoneal
      fibroproliferative tissue induced by a synthetic matrix. METHODS: Chronic
      inflammation was induced by placing polyether-polyurethane sponge discs in the
      abdominal cavity of anesthetized Swiss mice. Oral administration of propolis
      (500/mg/kg/day) by gavage started 24 hours after injury for four days. The effect
      of propolis on peritoneal permeability was evaluated through fluorescein
      diffusion rate 4 days post implantation. The effects of propolis on the
      inflammatory (myeloperoxidase and n-acetyl-beta-D-glucosaminidase activities and
      TNF-alpha levels), angiogenic (hemoglobin content-Hb), and fibrogenic (TGF-beta1
      and collagen deposition) components of the fibrovascular tissue in the implants
      were determined 5 days after the injury. RESULTS: Propolis was able to decrease
      intraperitoneal permeability. The time taken for fluorescence to peak in the
      systemic circulation was 20+/-1 min in the treated group in contrast with 15+/-1
      min in the control group. In addition, the treatment was shown to down-regulate
      angiogenesis (Hb content) and fibrosis by decreasing TGF-beta1 levels and
      collagen deposition in fibroproliferative tissue induced by the synthetic
      implants. Conversely, the treatment up-regulated inflammatory enzyme activities,
      TNF-alpha levels and gene expression of NOS2 and IFN-gamma (23 and 7 fold,
      respectively), and of FIZZ1 and YM1 (8 and 2 fold) when compared with the
      untreated group. CONCLUSIONS: These observations show for the first time the
      effects of propolis modulating intraperitoneal inflammatory angiogenesis in mice
      and disclose important action mechanisms of the compound (downregulation of
      angiogenic components and activation of murine macrophage pathways).

PMID- 24886377
TI  - Identification and characterization of microRNAs in the ovaries of multiple and
      uniparous goats (Capra hircus) during follicular phase.
AB  - BACKGROUND: Superior kidding rate is an important economic trait in production of
      meat goat, and ovulation rate is the precondition of kidding rate. MicroRNAs
      (miRNAs) play critical roles in almost all ovarian biological processes,
      including folliculogenesis, follicle development, follicle atresia, luteal
      development and regression. To find out the different ovarian activity and
      follicle recruitment with miRNA-mediated posttranscriptional regulation, the
      small RNAs expressed pattern in the ovarian tissues of multiple and uniparous
      Anhui White goats during follicular phase was analyzed using Solexa sequencing
      data. RESULTS: 1008 miRNAs co-expressed, 309 and 433 miRNAs specifically
      expressed in the ovaries of multiple and uniparous goats during follicular phase
      were identified. The 10 most highly expressed miRNAs in the multiple library were
      also the highest expressed in the uniparous library, and there were no
      significantly different between each other. The highest specific expressed miRNA
      in the multiple library was miR-29c, and the one in the uniparous library was miR
      6406. 35 novel miRNAs were predicted in total. GO annotation and KEGG Pathway
      analyses were implemented on target genes of all miRNA in two libraries. RT-PCR
      was applied to detect the expression level of 5 randomly selected miRNAs in
      multiple and uniparous hircine ovaries, and the results were consistent with the
      Solexa sequencing data. CONCLUSIONS: In the present study, the different
      expression of miRNAs in the ovaries of multiple and uniparous goats during
      follicular phase were characterized and investigated using deep sequencing
      technology. The result will help to further understand the role of miRNAs in
      kidding rate regulation and also may help to identify miRNAs which could be
      potentially used to increase hircine ovulation rate and kidding rate in the
      future.

PMID- 24886379
TI  - Diagnostic accuracy of semi-quantitative and quantitative culture techniques for
      the diagnosis of catheter-related infections in newborns and molecular typing of
      isolated microorganisms.
AB  - BACKGROUND: Catheter-related bloodstream infections (CR-BSIs) have become the
      most common cause of healthcare-associated bloodstream infections in neonatal
      intensive care units (ICUs). Microbiological evidence implicating catheters as
      the source of bloodstream infection is necessary to establish the diagnosis of CR
      BSIs. Semi-quantitative culture is used to determine the presence of
      microorganisms on the external catheter surface, whereas quantitative culture
      also isolates microorganisms present inside the catheter. The main objective of
      this study was to determine the sensitivity and specificity of these two
      techniques for the diagnosis of CR-BSIs in newborns from a neonatal ICU. In
      addition, PFGE was used for similarity analysis of the microorganisms isolated
      from catheters and blood cultures. METHODS: Semi-quantitative and quantitative
      methods were used for the culture of catheter tips obtained from newborns.
      Strains isolated from catheter tips and blood cultures which exhibited the same
      antimicrobial susceptibility profile were included in the study as positive cases
      of CR-BSI. PFGE of the microorganisms isolated from catheters and blood cultures
      was performed for similarity analysis and detection of clones in the ICU.
      RESULTS: A total of 584 catheter tips from 399 patients seen between November
      2005 and June 2012 were analyzed. Twenty-nine cases of CR-BSI were confirmed.
      Coagulase-negative staphylococci (CoNS) were the most frequently isolated
      microorganisms, including S. epidermidis as the most prevalent species (65.5%),
      followed by S. haemolyticus (10.3%), yeasts (10.3%), K. pneumoniae (6.9%), S.
      aureus (3.4%), and E. coli (3.4%). The sensitivity of the semi-quantitative and
      quantitative techniques was 72.7% and 59.3%, respectively, and specificity was
      95.7% and 94.4%. The diagnosis of CR-BSIs based on PFGE analysis of similarity
      between strains isolated from catheter tips and blood cultures showed 82.6%
      sensitivity and 100% specificity. CONCLUSION: The semi-quantitative culture
      method showed higher sensitivity and specificity for the diagnosis of CR-BSIs in
      newborns when compared to the quantitative technique. In addition, this method is
      easier to perform and shows better agreement with the gold standard, and should
      therefore be recommended for routine clinical laboratory use. PFGE may contribute
      to the control of CR-BSIs by identifying clusters of microorganisms in neonatal
      ICUs, providing a means of determining potential cross-infection between
      patients.

PMID- 24886378
TI  - Processes to manage analyses and publications in a phase III multicenter
      randomized clinical trial.
AB  - BACKGROUND: The timely publication of findings in peer-reviewed journals is a
      primary goal of clinical research. In clinical trials, the processes leading to
      publication can be complex from choice and prioritization of analytic topics
      through to journal submission and revisions. As little literature exists on the
      publication process for multicenter trials, we describe the development,
      implementation, and effectiveness of such a process in a multicenter trial.
      METHODS: The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C)
      trial included a data coordinating center (DCC) and clinical centers that
      recruited and followed more than 1,000 patients. Publication guidelines were
      approved by the steering committee, and the publications committee monitored the
      publication process from selection of topics to publication. RESULTS: A total of
      73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were
      closely tracked, the median time for analyses and drafting of manuscripts was 8
      months. The median time for data analyses was 5 months and the median time for
      manuscript drafting was 3 months. The median time for publications committee
      review, submission, and journal acceptance was 7 months, and the median time from
      analytic start to journal acceptance was 18 months. CONCLUSIONS: Effective
      publication guidelines must be comprehensive, implemented early in a trial, and
      require active management by study investigators. Successful collaboration, such
      as in the HALT-C trial, can serve as a model for others involved in
      multidisciplinary and multicenter research programs. TRIAL REGISTRATION: The HALT
      C Trial was registered with clinicaltrials.gov (NCT00006164).

PMID- 24886380
TI  - CYP4F2 genetic polymorphisms are associated with coronary heart disease in a
      Chinese population.
AB  - BACKGROUND: To explore the relationship between CYP4F2 gene polymorphism and
      coronary heart disease (CHD) in a Chinese Han population. METHODS: We selected
      440 CHD patients and 440 control subjects to perform a case - control study. Four
      SNPs (rs2108622, rs3093100, rs3093105 and rs3093135) in CYP4F2 gene were
      genotyped using polymerase chain reaction - restriction fragment length
      polymorphism (PCR - RFLP) methods. The genotype and haplotype distributions were
      compared between the case and the control group. RESULTS: We found both rs2108622
      and rs3093105 in CYP4F2 gene were associated with the risk for CHD (P <0.01).
      Haplotype analysis indicated that GGGT haplotype consisted by rs2108622-rs3093100
      rs3093105-rs3093135 was associated with CHD risk (OR = 4.367, 95% CI: 2.241 ~
      8.510; P < 0.001), but GGTA haplotype was associated with decreased risk for CHD
      (OR = 0.450, 95% CI: 0.111 ~ 0.777; P <0.001). CONCLUSION: CYP4F2 gene
      polymorphisms were associated with the risk of CHD in Chinese population.

PMID- 24886381
TI  - A new association test based on disease allele selection for case-control genome
      wide association studies.
AB  - BACKGROUND: Current robust association tests for case-control genome-wide
      association study (GWAS) data are mainly based on the assumption of some specific
      genetic models. Due to the richness of the genetic models, this assumption may
      not be appropriate. Therefore, robust but powerful association approaches are
      desirable. RESULTS: In this paper, we propose a new approach to testing for the
      association between the genotype and phenotype for case-control GWAS. This method
      assumes a generalized genetic model and is based on the selected disease allele
      to obtain a p-value from the more powerful one-sided test. Through a
      comprehensive simulation study we assess the performance of the new test by
      comparing it with existing methods. Some real data applications are also used to
      illustrate the use of the proposed test. CONCLUSIONS: Based on the simulation
      results and real data application, the proposed test is powerful and robust.

PMID- 24886382
TI  - Evaluation of a structured goal planning and tailored follow-up programme in
      rehabilitation for patients with rheumatic diseases: protocol for a pragmatic,
      stepped-wedge cluster randomized trial.
AB  - BACKGROUND: Comprehensive rehabilitation, involving health professionals from
      various disciplines, is widely used as an adjunct to pharmacological and surgical
      treatment in people with rheumatic diseases. However, the evidence for the
      clinical- and cost-effectiveness of such interventions is limited, and the
      majority of those who receive rehabilitation are back to their initial health
      status six to 12 months after discharge. METHODS/DESIGN: To evaluate the goal
      attainment, health effects and cost-effectiveness of a new rehabilitation
      programme compared to current traditional rehabilitation programmes for people
      with rheumatic diseases, a stepped-wedge cluster randomized trial will be
      performed. Patients admitted for rehabilitation at six centres in the south
      eastern part of Norway will be invited to participate. In the trial, six
      participating centres will switch from a control (current rehabilitation
      programme) to an intervention phase (the new rehabilitation programme) in a
      randomized order. Supported by recent research, the new programme will be a
      supplement to the existing programme at each centre, and will comprise four
      elements designed to enhance and support lifestyle changes introduced in the
      rehabilitation period: structured goal-planning, motivational interviewing, a
      self-help booklet and four follow-up telephone calls during the first five months
      following discharge. The primary outcome will be health-related quality of life
      and goal attainment, as measured by the Patient Generated Index directly before
      and after the rehabilitation stay, as well as after six and 12 months. Secondary
      outcomes will include self-reported pain, fatigue, a global assessment of disease
      activity and motivation for change (measured on 11-point numeric ratings scales),
      health-related quality of life as measured by the Short Form 36 Health Survey (SF
      36) and utility assessed by the SF6D utility index.The main analysis will be on
      an intention to treat basis and will assess the clinical- and cost-effectiveness
      of the structured goal planning and tailored follow-up rehabilitation programme
      for patients with rheumatic diseases. DISCUSSION: The findings will constitute an
      important contribution to more cost-effective- and evidence-based rehabilitation
      services for people with rheumatic diseases. TRIAL REGISTRATION: ISRCTN91433175.

PMID- 24886383
TI  - The variations of VP1 protein might be associated with nervous system symptoms
      caused by enterovirus 71 infection.
AB  - BACKGROUND: The VP1 protein of enterovirus 71 (EV71) is an important
      immunodominant protein which is responsible for host-receptor binding.
      Nevertheless, the relationship between VP1 and neurovirulence is still poorly
      understood. In this study, we investigated the relationship between mutation of
      VP1 and neurovirulent phenotype of EV71 infection. METHODS: One hundred and
      eighty-seven strains from Genbank were included, with a clear clinical
      background. They were divided into two groups, one with nervous system symptoms
      and one with no nervous system symptoms. After alignment, the significance of
      amino acid variation was determined by using the chi2 test and a phylogenetic
      tree was constructed with MEGA software (version 5.1). RESULTS: We showed no
      significant difference in neurovirulence between genotype B and C. Interestingly,
      we found that variations of E145G/Q, E164D/K and T292N/K were associated with
      nervous system infection in genotype B. In the case of genotype C, the N31D
      mutation increased the risk for nervous complications, whereas I262V mutation
      decreased the risk of nervous complications. We used a 3D model of VP1 to
      demonstrate the potential molecular basis for EV71 nervous system tropism.
      CONCLUSIONS: Distinct variations are shown to be associated with neurovirulent
      phenotype in the different genotype. Detection of variation in genotypes and
      subtypes may be important for the prediction of clinical outcomes.

PMID- 24886384
TI  - Rapid inflammasome activation in microglia contributes to brain disease in
      HIV/AIDS.
AB  - BACKGROUND: Human immunodeficiency virus type 1(HIV-1) infects and activates
      innate immune cells in the brain resulting in inflammation and neuronal death
      with accompanying neurological deficits. Induction of inflammasomes causes
      cleavage and release of IL-1beta and IL-18, representing pathogenic processes
      that underlie inflammatory diseases although their contribution HIV-associated
      brain disease is unknown. RESULTS: Investigation of inflammasome-associated genes
      revealed that IL-1beta, IL-18 and caspase-1 were induced in brains of HIV
      infected persons and detected in brain microglial cells. HIV-1 infection induced
      pro-IL-1beta in human microglia at 4 hr post-infection with peak IL-1beta release
      at 24 hr, which was accompanied by intracellular ASC translocation and caspase-1
      activation. HIV-dependent release of IL-1beta from a human macrophage cell line,
      THP-1, was inhibited by NLRP3 deficiency and high extracellular [K+]. Exposure of
      microglia to HIV-1 gp120 caused IL-1beta production and similarly, HIV-1 envelope
      pseudotyped viral particles induced IL-1beta release, unlike VSV-G pseudotyped
      particles. Infection of cultured feline macrophages by the related lentivirus,
      feline immunodeficiency virus (FIV), also resulted in the prompt induction of IL
      1beta. In vivo FIV infection activated multiple inflammasome-associated genes in
      microglia, which was accompanied by neuronal loss in cerebral cortex and
      neurological deficits. Multivariate analyses of data from FIV-infected and
      uninfected animals disclosed that IL-1beta, NLRP3 and caspase-1 expression in
      cerebral cortex represented key molecular determinants of neurological deficits.
      CONCLUSIONS: NLRP3 inflammasome activation was an early and integral aspect of
      lentivirus infection of microglia, which was associated with lentivirus-induced
      brain disease. Inflammasome activation in the brain might represent a potential
      target for therapeutic interventions in HIV/AIDS.

PMID- 24886385
TI  - Health-related quality of life and risk of colorectal cancer recurrence and All
      cause death among advanced stages of colorectal cancer 1-year after diagnosis.
AB  - BACKGROUND: The study aimed to examine the association between health-related
      quality of life (HRQOL) assessed with overall survival (OS) and recurrence after
      diagnosis of colorectal cancer (CRC). METHODS: Overall 160 patients with advanced
      stage CRC were recruited in an observational study and completed the generic and
      condition-specific HRQOL questionnaires at the colorectal specialist outpatient
      clinic in Hong Kong, between 10/2009 and 07/2010. Socio-demographic and clinical
      characteristics including duration since diagnosis, primary tumor location and
      treatment modality, were collected to serve as predictor variables in regression
      models. All-cause death or CRC recurrence was the event of interest. Association
      between HRQOL with OS was assessed using Cox regression. Association between
      HRQOL and CRC recurrence was further modeled by competing-risks regression
      adjusted for the competing-risks of death from any cause. RESULTS: After a median
      follow-up of 23 months, there were 22 (16.1%) incidents of CRC recurrence and 15
      (9.4%) deaths. Decreased physical functioning (hazard ratios, HR = 0.917, 95%
      CI:0.889-0.981) and general health of domains in SF-12 (HR = 0.846, 95% CI:0.746
      0.958) or SF-6D scores (HR = 0.010, 95% CI:0.000-0.573) were associated with an
      increased risk of death, with adjustment of patients' characteristics. Increased
      vitality (HR = 1.151, 95% CI:1.027-1.289) and mental health (HR = 1.128, 95%
      CI:1.005-1.265) were associated with an increased likelihood of death. In models
      adjusted for competing-risk of death, those with worse HRQOL was not associated
      with increased risk of CRC recurrence. CONCLUSIONS: Although self-reported HRQOL
      was not a significant prognostic factor for CRC recurrence, the HRQOL provided
      independent prognostic value about mortality in patients with advanced stage of
      CRC.

PMID- 24886386
TI  - DNA methylation signatures in cord blood associated with maternal gestational
      weight gain: results from the ALSPAC cohort.
AB  - BACKGROUND: Epigenetic changes could mediate the association of maternal pre
      pregnancy body mass index (BMI) and gestational weight gain (GWG) with adverse
      offspring outcomes. However, studies in humans are lacking. Here, we examined the
      association of maternal pre-pregnancy BMI and GWG in different periods of
      pregnancy with cytosine-guanine (CpG) dinucleotide site methylation differences
      in newborn cord blood DNA from 88 participants in the Avon Longitudinal Study of
      Parents and Children (ALSPAC) cohort using the Illumina GoldenGate Panel I.
      Pyrosequencing was used for validation of the top associated locus and for
      replication in 170 non-overlapping mother-offspring pairs from the ALSPAC cohort.
      RESULTS: After correction for multiple testing greater GWG in early pregnancy
      (between 0 to 18 weeks of gestation) was associated with increased DNA
      methylation levels in four CpG sites at MMP7, KCNK4, TRPM5 and NFKB1 genes
      (difference in methylation >5% per 400 g/week greater GWG) (q values 0.023 
      0.065). Pre-pregnancy BMI and GWG in mid- or late pregnancy were not associated
      with differential DNA methylation at any CpG site. Pyrosequencing showed that
      greater GWG in early pregnancy was associated with increased DNA methylation
      levels at the top associated CpG site at MMP7, although association did not reach
      statistical significance (p = 0.302). Greater GWG in mid- (p = 0.167) and late
      pregnancy (p = 0.037) were also associated with increased DNA methylation levels
      at the MMP7 CpG site. In addition, newborns of mothers who exceeded the IoM
      recommended GWG had higher DNA methylation levels at the MMP7 CpG site than those
      of mothers with IoM-recommended GWG (p = 0.080). We failed to replicate findings.
      CONCLUSIONS: Greater GWG in early pregnancy was associated with increased
      methylation at CpG sites at MMP7, KCNK4, TRPM5 and NFKB1 genes in offspring cord
      blood DNA. The specific association of GWG in early pregnancy with the top
      associated CpG site at MMP7 was not validated using Pyrosequencing and it did not
      replicate. However, given the potential functional relevancy of the four
      identified loci, we advocate further exploration of them in larger studies.

PMID- 24886387
TI  - A comparative analysis of genetic variation in rootstocks and scions of old olive
      trees - a window into the history of olive cultivation practices and past genetic
      variation.
AB  - BACKGROUND: Past clonal propagation of olive trees is intimately linked to
      grafting. However, evidence on grafting in ancient trees is scarce, and not much
      is known about the source of plant material used for rootstocks. Here, the Simple
      Sequence Repeat (SSR) marker technique was used to study genetic diversity of
      rootstocks and scions in ancient olive trees from the Levant and its implications
      for past cultivation of olives. Leaf samples were collected from tree canopies
      (scions) and shoots growing from the trunk base (suckers). A total of 310 trees
      were sampled in 32 groves and analyzed with 14 SSR markers. RESULTS: In 82.7% of
      the trees in which both scion and suckers could be genotyped, these were
      genetically different, and thus suckers were interpreted to represent the
      rootstock of grafted trees. Genetic diversity values were much higher among
      suckers than among scions, and 194 and 87 multi-locus genotypes (MLGs) were found
      in the two sample groups, respectively. Only five private alleles were found
      among scions, but 125 among suckers. A frequency analysis revealed a bimodal
      distribution of genetic distance among MLGs, indicating the presence of somatic
      mutations within clones. When assuming that MLGs differing by one mutation are
      identical, scion and sucker MLGs were grouped in 20 and 147 multi-locus lineages
      (MLLs). The majority of scions (90.0%) belonged to a single common MLL, whereas
      50.5% of the suckers were single-sample MLLs. However, one MLL was specific to
      suckers and found in 63 (22.6%) of the samples. CONCLUSIONS: Our results provide
      strong evidence that the majority of olive trees in the study are grafted, that
      the large majority of scions belong to a single ancient cultivar containing
      somatic mutations, and that the widespread occurrence of one sucker genotype may
      imply rootstock selection. For the majority of grafted trees it seems likely that
      saplings were used as rootstocks; their genetic diversity probably is best
      explained as the result of a long history of sexual reproduction involving
      cultivated, feral and wild genotypes.

PMID- 24886388
TI  - Cysteine proteinases from papaya (Carica papaya) in the treatment of experimental
      Trichuris suis infection in pigs: two randomized controlled trials.
AB  - BACKGROUND: Cysteine proteinases (CPs) from papaya (Carica papaya) possess
      anthelmintic properties against human soil-transmitted helminths (STH, Ascaris
      lumbricoides, Trichuris trichiura and hookworm), but there is a lack of
      supportive and up-to-date efficacy data. We therefore conducted two randomized
      controlled trials in pigs to assess the efficacy of papaya CPs against
      experimental infections with T. suis. METHODS: First, we assessed efficacy by
      means of egg (ERR) and adult worm reduction rate (WRR) of a single-oral dose of
      450 MUmol active CPs (CP450) against low (inoculum of 300 eggs) and high
      (inoculum of 3,000 eggs) intensity T. suis infections and compared the efficacy
      with those obtained after a single-oral dose of 400 mg albendazole (ALB). In the
      second trial, we determined and compared the efficacy of a series of CP doses (45
      [CP45], 115 [CP115], 225 [CP225], and 450 [CP450] MUmol) against high intensity
      infections. RESULTS: CP450 was highly efficacious against both levels of
      infection intensity, resulting in ERR and WRR of more than 97%. For both levels
      of infection intensity, CP450 was significantly more efficacious compared to ALB
      by means of WRR (low infection intensity: 99.0% vs. 39.0%; high infection
      intensity; 97.4% vs. 23.2%). When the efficacy was assessed by ERR, a significant
      difference was only observed for high intensity infections, CP450 being more
      efficacious than ALB (98.9% vs. 59.0%). For low infection intensities, there was
      no significant difference in ERR between CP450 (98.3%) and ALB (64.4%). The
      efficacy of CPs increased as a function of increasing dose. When determined by
      ERR, the efficacy ranged from 2.1% for CP45 to 99.2% for CP450. For WRR the
      results varied from -14.0% to 99.0%, respectively. Pairwise comparison revealed a
      significant difference in ERR and WRR only between CP45 and CP450, the latter
      being more efficacious. CONCLUSIONS: A single dose of 450 MUmol CPs provided
      greater efficacy against T. suis infections in pigs than a single-oral dose of
      400 mg ALB. Although these results highlight the possibility of papaya CPs for
      controlling human STH, further development is needed in order to obtain and
      validate an oral formulation for human application.

PMID- 24886389
TI  - Quantifying cross-border movements and migrations for guiding the strategic
      planning of malaria control and elimination.
AB  - BACKGROUND: Identifying human and malaria parasite movements is important for
      control planning across all transmission intensities. Imported infections can
      reintroduce infections into areas previously free of infection, maintain
      'hotspots' of transmission and import drug resistant strains, challenging
      national control programmes at a variety of temporal and spatial scales. Recent
      analyses based on mobile phone usage data have provided valuable insights into
      population and likely parasite movements within countries, but these data are
      restricted to sub-national analyses, leaving important cross-border movements
      neglected. METHODS: National census data were used to analyse and model cross
      border migration and movement, using East Africa as an example. 'Hotspots' of
      origin-specific immigrants from neighbouring countries were identified for Kenya,
      Tanzania and Uganda. Populations of origin-specific migrants were compared to
      distance from origin country borders and population size at destination, and
      regression models were developed to quantify and compare differences in migration
      patterns. Migration data were then combined with existing spatially-referenced
      malaria data to compare the relative propensity for cross-border malaria movement
      in the region. RESULTS: The spatial patterns and processes for immigration were
      different between each origin and destination country pair. Hotspots of
      immigration, for example, were concentrated close to origin country borders for
      most immigrants to Tanzania, but for Kenya, a similar pattern was only seen for
      Tanzanian and Ugandan immigrants. Regression model fits also differed between
      specific migrant groups, with some migration patterns more dependent on
      population size at destination and distance travelled than others. With these
      differences between immigration patterns and processes, and heterogeneous
      transmission risk in East Africa and the surrounding region, propensities to
      import malaria infections also likely show substantial variations. CONCLUSION:
      This was a first attempt to quantify and model cross-border movements relevant to
      malaria transmission and control. With national census available worldwide, this
      approach can be translated to construct a cross-border human and malaria movement
      evidence base for other malaria endemic countries. The outcomes of this study
      will feed into wider efforts to quantify and model human and malaria movements in
      endemic regions to facilitate improved intervention planning, resource allocation
      and collaborative policy decisions.

PMID- 24886390
TI  - Counseling on lifestyle habits in the United States and Sweden: a report
      comparing primary care health professionals' perspectives on lifestyle counseling
      in terms of scope, importance and competence.
AB  - BACKGROUND: The role of primary care professionals in lifestyle counseling for
      smoking, alcohol consumption, physical activity, and diet is receiving attention
      at the national level in many countries. The U. S. and Sweden are two countries
      currently establishing priorities in these areas. A previously existing
      international research collaboration provides a unique opportunity to study this
      issue. METHODS: Data from a national survey in Sweden and a study in rural
      Upstate New York were compared to contrast the perspectives, attitudes, and
      practice of primary care professionals in the two countries. Answers to four key
      questions on counseling for tobacco use, alcohol consumption, physical activity,
      and eating habits were compared. RESULTS: The response rates were 71% (n=180) and
      89% (n=86) in the Sweden and the U.S. respectively. U.S. professionals rated
      counseling "very important" significantly more frequently than Swedish
      professionals for tobacco (99% versus 92%, p<.0001), physical activity (90%
      versus 79%, p=.04), and eating habits (86% versus 69%, p=.003). U.S.
      professionals also reported giving "very much" counseling more frequently for
      these same three endpoints than did the Swedish professionals (tobacco 81% versus
      38%, p<.0001, physical activity 64% versus 31%, p<.0001, eating 59% versus 34%,
      p=.0001). Swedish professionals also rated their level of expertise in providing
      counseling significantly lower than did their U.S. counterparts for all four
      endpoints. A higher percentage of U.S. professionals expressed a desire to
      increase levels of counseling "very much", but only significantly so for eating
      habits (42% versus 28%, p=.037). CONCLUSIONS: The study demonstrates large
      differences between the extent that Swedish and American primary care
      professionals report being engaged in counseling on lifestyle issues, how
      important they perceive counseling to be, and what expertise they possess in this
      regard. Explanations might be found in inter-professional attitudes, the
      organization of healthcare, including the method of reimbursement, traditions of
      preventive healthcare, and cultural differences between the two countries.
      Further studies are needed to explore these questions, with the aim of
      facilitating improved lifestyle counseling in primary care.

PMID- 24886391
TI  - Histological, cellular and behavioral assessments of stroke outcomes after
      photothrombosis-induced ischemia in adult mice.
AB  - BACKGROUND: Following the onset of focal ischemic stroke, the brain experiences a
      series of alterations including infarct evolvement, cellular proliferation in the
      penumbra, and behavioral deficits. However, systematic study on the temporal and
      spatial dependence of these alterations has not been provided. RESULTS: Using
      multiple approaches, we assessed stroke outcomes by measuring brain injury,
      dynamic cellular and glial proliferation, and functional deficits at different
      times up to two weeks after photothrombosis (PT)-induced ischemic stroke in adult
      mice. Results from magnetic resonance imaging (MRI) and Nissl staining showed a
      maximal infarction, and brain edema and swelling 1-3 days after PT. The rate of
      Bromodeoxyuridine (Brdu)-labeled proliferating cell generation is spatiotemporal
      dependent in the penumbra, with the highest rate in post ischemic days 3-4, and
      higher rate of proliferation in the region immediate to the ischemic core than in
      the distant region. Similar time-dependent generation of proliferating GFAP+
      astrocytes and Iba1+ microglia/macrophage were observed in the penumbra. Using
      behavioral tests, we showed that PT resulted in the largest functional deficits
      during post ischemic days 2-4. CONCLUSION: Our study demonstrated that first a
      few days is a critical period that causes brain expansion, cellular proliferation
      and behavioral deficits in photothrombosis-induced ischemic model, and
      proliferating astrocytes only have a small contribution to the pools of
      proliferating cells and reactive astrocytes.

PMID- 24886392
TI  - Implementation of evidence-based antenatal care in Mozambique: a cluster
      randomized controlled trial: study protocol.
AB  - BACKGROUND: Antenatal care (ANC) reduces maternal and perinatal morbidity and
      mortality directly through the detection and treatment of pregnancy-related
      illnesses, and indirectly through the detection of women at increased risk of
      delivery complications. The potential benefits of quality antenatal care services
      are most significant in low-resource countries where morbidity and mortality
      levels among women of reproductive age and neonates are higher.WHO developed an
      ANC model that recommended the delivery of services scientifically proven to
      improve maternal, perinatal and neonatal outcomes. The aim of this study is to
      determine the effect of an intervention designed to increase the use of the
      package of evidence-based services included in the WHO ANC model in Mozambique.
      The primary hypothesis is that the intervention will increase the use of evidence
      based practices during ANC visits in comparison to the standard dissemination
      channels currently used in the country. METHODS: This is a demonstration project
      to be developed through a facility-based cluster randomized controlled trial with
      a stepped wedge design. The intervention was tailored, based on formative
      research findings, to be readily applicable to local prenatal care services and
      acceptable to local pregnant women and health providers. The intervention
      includes four components: the provision of kits with all necessary medicines and
      laboratory supplies for ANC (medical and non-medical equipment), a storage
      system, a tracking system, and training sessions for health care providers. Ten
      clinics were selected and will start receiving the intervention in a random
      order. Outcomes will be computed at each time point when a new clinic starts the
      intervention. The primary outcomes are the delivery of selected health care
      practices to women attending the first ANC visit, and secondary outcomes are the
      delivery of selected health care practices to women attending second and higher
      ANC visits as well as the attitude of midwives in relation to adopting the
      practices. This demonstration project is pragmatic in orientation and will be
      conducted under routine conditions. DISCUSSION: There is an urgent need for
      effective and sustainable scaling-up approaches of health interventions in low
      resource countries. This can only be accomplished by the engagement of the
      country's health stakeholders at all levels. This project aims to achieve
      improvement in the quality of antenatal care in Mozambique through the
      implementation of a multifaceted intervention on three levels: policy,
      organizational and health care delivery levels. The implementation of the trial
      will probably require a change in accountability and behaviour of health care
      providers and we expect this change in 'habits' will contribute to obtaining
      reliable health indicators, not only related to research issues, but also to
      health care outcomes derived from the new health care model. At policy level, the
      results of this study may suggest a need for revision of the supply chain
      management system. Given that supply chain management is a major challenge for
      many low-resource countries, we envisage that important lessons on how to improve
      the supply chain in Mozambique and other similar settings, will be drawn from
      this study. TRIAL REGISTRATION: Pan African Clinical Trial Registry database.
      Identification number: PACTR201306000550192.

PMID- 24886393
TI  - Road map to scaling-up: translating operations research study's results into
      actions for expanding medical abortion services in rural health facilities in
      Nepal.
AB  - BACKGROUND: Identifying unsafe abortion among the major causes of maternal deaths
      and respecting the rights to health of women, in 2002, the Nepali parliament
      liberalized abortion up to 12 weeks of pregnancy on request. However, enhancing
      women's awareness on and access to safe and legal abortion services, particularly
      in rural areas, remains a challenge in Nepal despite a decade of the initiation
      of safe abortion services. METHODS: Between January 2011 and December 2012, an
      operations research study was carried out using quasi-experimental design to
      determine the effectiveness of engaging female community health volunteers,
      auxiliary nurse midwives, and nurses to provide medical abortion services from
      outreach health facilities to increase the accessibility and acceptability of
      women to medical abortion. This paper describes key components of the operations
      research study, key research findings, and follow-up actions that contributed to
      create a conducive environment and evidence in scaling up medical abortion
      services in rural areas of Nepal. RESULTS: It was found that careful planning and
      implementation, continuous advocacy, and engagement of key stakeholders,
      including key government officials, from the planning stage of study is not only
      crucial for successful completion of the project but also instrumental for
      translating research results into action and policy change. While challenges
      remained at different levels, medical abortion services delivered by nurses and
      auxiliary nurse midwives working at rural outreach health facilities without
      oversight of physicians was perceived to be accessible, effective, and of good
      quality by the service providers and the women who received medical abortion
      services from these rural health facilities. CONCLUSIONS: This research provided
      further evidence and a road-map for expanding medical abortion services to rural
      areas by mid-level service providers in minimum clinical settings without the
      oversight of physicians, thus reducing complications and deaths due to unsafe
      abortion.

PMID- 24886394
TI  - A novel flow cytometry-based cell capture platform for the detection, capture and
      molecular characterization of rare tumor cells in blood.
AB  - BACKGROUND: Personalized cancer treatment relies on the accurate detection of
      actionable genomic aberrations in tumor cells. Circulating tumor cells (CTCs)
      could provide an alternative genetic resource for diagnosis; however, the
      technical difficulties in isolating and analyzing rare CTCs have limited progress
      to date. In this preclinical study, we aimed to develop an improved capture
      system for molecular characterization of CTCs based on a novel cell sorting
      technology. METHODS: We developed a cell capture platform using On-chip Sort (On
      Chip Biotechnologies), a novel bench-top cell sorter equipped with a disposable
      microfluidic chip. Spike-in experiments comprising a series of lung cancer cell
      lines with varying epithelial cell adhesion molecule (EpCAM) expression levels
      were conducted to assess the capture and purification efficiency of the platform.
      Samples were negatively enriched using anti-CD45-coated magnetic beads to remove
      white blood cells, followed by sample fixation and labeling. The enriched and
      labeled samples were then sorted by On-chip Sort based on cytokeratin, vimentin,
      and CD45 expression. Captured cells were immediately subjected to whole genome
      amplification followed by mutation analysis using deep targeted sequencing, and
      copy number analysis using quantitative polymerase chain reaction (qPCR).
      RESULTS: Spike-in experiments revealed an excellent overall mean capture rate of
      70.9%. A 100% success rate in the detection of EGFR, KRAS and BRAF mutations from
      captured cells was achieved using pyrosequencing and deep sequencing. The mutant
      variant detection rates were markedly higher than those obtained with the
      CellSearch profile kit. qPCR analysis of amplified DNA demonstrated reproducible
      detection of copy number changes of the EGFR in captured tumor cells.
      CONCLUSIONS: Using a novel cell sorter, we established an efficient and
      convenient platform for the capture of CTCs. Results of a proof-of-principle
      preclinical study indicated that this platform has potential for the molecular
      characterization of captured CTCs from patients.

PMID- 24886395
TI  - Combined immunization using DNA-Sm14 and DNA-Hsp65 increases CD8+ memory T cells,
      reduces chronic pathology and decreases egg viability during Schistosoma mansoni
      infection.
AB  - BACKGROUND: Schistosomiasis is one of the most important neglected diseases found
      in developing countries and affects 249 million people worldwide. The development
      of an efficient vaccination strategy is essential for the control of this
      disease. Previous work showed partial protection induced by DNA-Sm14 against
      Schistosoma mansoni infection, whereas DNA-Hsp65 showed immunostimulatory
      properties against infectious diseases, autoimmune diseases, cancer and
      antifibrotic properties in an egg-induced granuloma model. METHODS: C57BL/6 mice
      received 4 doses of DNA-Sm14 (100 MUg/dose) and DNA-Hsp65 (100 MUg/dose),
      simultaneously administrated, or DNA-Sm14 alone, once a week, during four weeks.
      Three groups were included: 1- Control (no immunization); 2- DNA-Sm14; 3- DNA
      Sm14/DNA-Hsp65. Two weeks following last immunization, animals were challenged
      subcutaneously with 30 cercariae. Fifteen, 48 and 69 days after infection
      splenocytes were collected to evaluate the number of CD8+ memory T cells
      (CD44(high)CD62(low)) using flow cytometry. Forty-eight days after challenge
      adult worms were collected by portal veins perfusion and intestines were
      collected to analyze the intestinal egg viability. Histological,
      immunohistochemical and soluble quantification of collagen and alpha-SMA
      accumulation were performed on the liver. RESULTS: In the current work, we tested
      a new vaccination strategy using DNA-Sm14 with DNA-Hsp65 to potentiate the
      protection against schistosomiasis. Combined vaccination increased the number of
      CD8+ memory T cells and decreased egg viability on the intestinal wall of
      infected mice. In addition, simultaneous vaccination with DNA-Sm14/DNA-Hsp65
      reduced collagen and alpha-SMA accumulation during the chronic phase of granuloma
      formation. CONCLUSION: Simultaneous vaccination with DNA-Sm14/DNA-Hsp65 showed an
      immunostimulatory potential and antifibrotic property that is associated with the
      reduction of tissue damage on Schistosoma mansoni experimental infection.

PMID- 24886396
TI  - Sublobectomy versus lobectomy for stage IA (T1a) non-small-cell lung cancer: a
      meta-analysis study.
AB  - BACKGROUND: Although lobectomy is considered the standard surgical treatment for
      the majority of patients with non-small-cell lung cancer (NSCLC), the operation
      project for patients with stage IA NSCLC (T1a, tumor diameter<=2 cm) remains
      controversial. Sublobectomy is appropriate only in certain patients as many
      doctors consider it to be overtreatment. We evaluated the five-year overall
      survival rate of sublobectomy and lobectomy for stage IA NSCLC (T1a, tumor
      diameter<=2 cm) through a meta-analysis. METHODS: The five-year overall survival
      rate (OS) of stage IA (T1a) NSCLC after sublobectomy (including wedge resection
      and segmentectomy) and lobectomy were compared. We also compared the OS of stage
      IA (T1a) NSCLC after segmentectomy and lobectomy. The log (hazard ratio, ln (HR))
      and its standard error (SE) were used as the outcome measure for data combining.
      RESULTS: There were 12 eligible studies published between 1994 and 2013 in which
      the total number of participants was 18,720. When compared to lobectomy, there
      was a statistically significant difference of sublobectomy on OS of stage IA
      (T1a) NSCLC patients (HR 1.38; 95% confidence interval (95% CI), 1.19 to 1.61;
      P<0.0001). For the comparison between segmentectomy and lobectomy, there was also
      a statistically significant difference of segmentectomy alone on OS of stage IA
      (T1a) NSCLC patients (HR 1.48; 95% CI: 1.27 to 1.73; P<0.00001) CONCLUSIONS: We
      have concluded that in stage IA (T1a) patients sublobectomy, including
      segmentectomy and wedge resection, causes a lower survival rate than lobectomy.

PMID- 24886397
TI  - Merging metagenomics and geochemistry reveals environmental controls on
      biological diversity and evolution.
AB  - BACKGROUND: The metabolic strategies employed by microbes inhabiting natural
      systems are, in large part, dictated by the physical and geochemical properties
      of the environment. This study sheds light onto the complex relationship between
      biology and environmental geochemistry using forty-three metagenomes collected
      from geochemically diverse and globally distributed natural systems. It is widely
      hypothesized that many uncommonly measured geochemical parameters affect
      community dynamics and this study leverages the development and application of
      multidimensional biogeochemical metrics to study correlations between
      geochemistry and microbial ecology. Analysis techniques such as a Markov cluster
      based measure of the evolutionary distance between whole communities and a
      principal component analysis (PCA) of the geochemical gradients between
      environments allows for the determination of correlations between microbial
      community dynamics and environmental geochemistry and provides insight into which
      geochemical parameters most strongly influence microbial biodiversity. RESULTS:
      By progressively building from samples taken along well defined geochemical
      gradients to samples widely dispersed in geochemical space this study reveals
      strong links between the extent of taxonomic and functional diversification of
      resident communities and environmental geochemistry and reveals temperature and
      pH as the primary factors that have shaped the evolution of these communities.
      Moreover, the inclusion of extensive geochemical data into analyses reveals new
      links between geochemical parameters (e.g. oxygen and trace element availability)
      and the distribution and taxonomic diversification of communities at the
      functional level. Further, an overall geochemical gradient (from multivariate
      analyses) between natural systems provides one of the most complete predictions
      of microbial taxonomic and functional composition. CONCLUSIONS: Clustering based
      on the frequency in which orthologous proteins occur among metagenomes
      facilitated accurate prediction of the ordering of community functional
      composition along geochemical gradients, despite a lack of geochemical input. The
      consistency in the results obtained from the application of Markov clustering and
      multivariate methods to distinct natural systems underscore their utility in
      predicting the functional potential of microbial communities within a natural
      system based on system geochemistry alone, allowing geochemical measurements to
      be used to predict purely biological metrics such as microbial community
      composition and metabolism.

PMID- 24886398
TI  - One year follow-up of a pragmatic multi-centre randomised controlled trial of a
      group-based fatigue management programme (FACETS) for people with multiple
      sclerosis.
AB  - BACKGROUND: Fatigue is one of the most common and debilitating symptoms of
      multiple sclerosis (MS). The aim was to evaluate the effectiveness at 1-year
      follow-up of a manualised group-based programme ('FACETS') for managing MS
      fatigue. METHODS: One-year follow-up of a pragmatic multi-centre randomised
      controlled trial. People with MS and significant fatigue were randomised to
      FACETS plus current local practice (FACETS) or current local practice alone
      (CLP), using concealed computer-generated randomisation. Participant blinding was
      not possible. Primary outcome measures were fatigue severity (Global Fatigue
      Severity subscale of the Fatigue Assessment Instrument), self-efficacy (MS
      Fatigue Self-Efficacy) and disease-specific quality of life (MS Impact Scale).
      RESULTS: Between May 2008 and November 2009, 164 participants were randomised.
      Primary outcome data were available at 1 year for 131 (80%). The benefits
      demonstrated at 4-months in the FACETS arm for fatigue severity and self-efficacy
      largely persisted, with a slight reduction in standardised effect sizes (SES) (
      0.29, p = 0.06 and 0.34, p = 0.09, respectively). There was a significant
      difference on the MS Impact Scale favouring FACETS that had not been present at 4
      months (SES -0.24, p = 0.046). No adverse events were reported. CONCLUSIONS:
      Improvements in fatigue severity and self-efficacy at 4-months follow-up
      following attendance of FACETS were mostly sustained at 1 year with additional
      improvements in MS impact. The FACETS programme provides modest long-term
      benefits to people with MS-fatigue. TRIAL REGISTRATION: ISRCTN76517470.

PMID- 24886399
TI  - Impact of PermaNet 3.0 on entomological indices in an area of pyrethroid
      resistant Anopheles gambiae in south-western Nigeria.
AB  - BACKGROUND: PermaNet(r) 3.0 is an insecticide synergist-combination long-lasting
      insecticidal net designed to have increased efficacy against malaria vectors with
      metabolic resistance, even when combined with kdr. The current study reports on
      the impact of this improved tool on entomological indices in an area with
      pyrethroid-resistant malaria vectors in Nigeria. METHODS: Baseline entomological
      indices across eight villages in Remo North LGA of Ogun State provided the basis
      for selection of three villages (Ilara, Irolu and Ijesa) for comparing the
      efficacy of PermaNet(r) 3.0 (PN3.0), PermaNet(r) 2.0 (PN2.0) and untreated
      polyester nets as a control (UTC). In each case, nets were distributed to cover
      all sleeping spaces and were evaluated for insecticidal activity on a 3-monthly
      basis. Collection of mosquitoes was conducted monthly via window traps and indoor
      resting catches. The arithmetic means of mosquito catches per house,
      entomological inoculation rates before and during the intervention were compared
      as well as three other outcome parameters: the mean mosquito blood feeding rate,
      mean mortality and mean parity rates. RESULTS: Anopheles gambiae s.l. was the
      main malaria vector in the three villages, accounting for >98% of the Anopheles
      population and found in appreciable numbers for 6-7 months. Deltamethrin,
      permethrin and lambdacyhalothrin resistance were confirmed at Ilara, Irolu and
      Ijesa. The kdr mutation was the sole resistance mechanism at Ilara, whereas kdr
      plus P450-based metabolic mechanisms were detected at Irolu and Ijesa. Bioassays
      repeated on domestically used PN 2.0 and PN 3.0 showed persistent optimal (100%)
      bio-efficacy for both net types after the 3rd, 6th, 9th and 12th month following
      net distribution. The use of PN 3.0 significantly reduced mosquito densities with
      a 'mass killing' effect inside houses. Households with PN 3.0 also showed reduced
      blood feeding as well as lower mosquito parity and sporozoite rates compared to
      the PN 2.0 and the UTC villages. A significant reduction in the entomological
      inoculation rate was detected in both the PN 2.0 village (75%) and PN 3.0 village
      (97%) post LLIN-distribution and not in the UTC village. CONCLUSION: The study
      confirms the efficacy of PN 3.0 in reducing malaria transmission compared to
      pyrethroid-only LLINs in the presence of malaria vectors with P450-based
      metabolic- resistance mechanisms.

PMID- 24886400
TI  - Modeling the transmission of community-associated methicillin-resistant
      Staphylococcus aureus: a dynamic agent-based simulation.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has been a deadly
      pathogen in healthcare settings since the 1960s, but MRSA epidemiology changed
      since 1990 with new genetically distinct strain types circulating among
      previously healthy people outside healthcare settings. Community-associated (CA)
      MRSA strains primarily cause skin and soft tissue infections, but may also cause
      life-threatening invasive infections. First seen in Australia and the U.S., it is
      a growing problem around the world. The U.S. has had the most widespread CA-MRSA
      epidemic, with strain type USA300 causing the great majority of infections.
      Individuals with either asymptomatic colonization or infection may transmit CA
      MRSA to others, largely by skin-to-skin contact. Control measures have focused on
      hospital transmission. Limited public health education has focused on care for
      skin infections. METHODS: We developed a fine-grained agent-based model for
      Chicago to identify where to target interventions to reduce CA-MRSA transmission.
      An agent-based model allows us to represent heterogeneity in population behavior,
      locations and contact patterns that are highly relevant for CA-MRSA transmission
      and control. Drawing on nationally representative survey data, the model
      represents variation in sociodemographics, locations, behaviors, and physical
      contact patterns. Transmission probabilities are based on a comprehensive
      literature review. RESULTS: Over multiple 10-year runs with one-hour ticks, our
      model generates temporal and geographic trends in CA-MRSA incidence similar to
      Chicago from 2001 to 2010. On average, a majority of transmission events occurred
      in households, and colonized rather than infected agents were the source of the
      great majority (over 95%) of transmission events. The key findings are that
      infected people are not the primary source of spread. Rather, the far greater
      number of colonized individuals must be targeted to reduce transmission.
      CONCLUSIONS: Our findings suggest that current paradigms in MRSA control in the
      United States cannot be very effective in reducing the incidence of CA-MRSA
      infections. Furthermore, the control measures that have focused on hospitals are
      unlikely to have much population-wide impact on CA-MRSA rates. New strategies
      need to be developed, as the incidence of CA-MRSA is likely to continue to grow
      around the world.

PMID- 24886401
TI  - Research to stop tobacco deaths.
AB  - In 2003, governments adopted the Framework Convention on Tobacco Control, the
      world's first global health treaty. In the decade since the treaty was adopted by
      178 member states of the World Health Organization, there have been substantial
      achievements in reducing tobacco use around the world. Research and evidence on
      the impact of interventions and policies have helped drive this policy progress.
      An increased and sustained focus on research is needed in the future to ensure
      that the gains of the global tobacco control movement are maintained,
      particularly in low- and middle-income countries, which are affected most
      strongly by the tobacco epidemic. In addition to current priorities, greater
      attention is needed to research related to trade agreements, prevention among
      girls, and the appropriate response to nicotine-based noncombustibles (including
      e-cigarettes). 

PMID- 24886402
TI  - Day Hospital Mentalization-Based Treatment (MBT-DH) versus treatment as usual in
      the treatment of severe borderline personality disorder: protocol of a randomized
      controlled trial.
AB  - BACKGROUND: Severe borderline personality disorder is associated with a very high
      psychosocial and economic burden. Current treatment guidelines suggest that
      several manualized treatments, including day hospital Mentalization-Based
      Treatment (MBT-DH), are effective in these patients. However, only two randomized
      controlled trials have compared manualized MBT-DH with treatment as usual. Given
      the relative paucity of data supporting the efficacy and cost-effectiveness of
      MBT-DH, the possible influence of researcher allegiance in one of the trials, and
      potential problems with the generalization of findings to mental health systems
      in other countries, this multi-site randomized trial aims to investigate the
      efficacy and cost-effectiveness of manualized MBT-DH compared to manualized
      specialist treatment as usual in The Netherlands. METHODS/DESIGN: The trial is
      being conducted at two sites in The Netherlands. Patients with a DSM-IV-TR
      diagnosis of borderline personality disorder and a score of >= 20 on the
      Borderline Personality Disorder Severity Index were randomly allocated to MBT-DH
      or treatment as usual. The MBT-DH program consists of a maximum of 18 months'
      intensive treatment, followed by a maximum of 18 months of maintenance therapy.
      Specialist treatment as usual is provided by the City Crisis Service in
      Amsterdam, a service that specializes in treating patients with personality
      disorders, offering manualized, non-MBT interventions including family
      interventions, Linehan training, social skills training, and pharmacotherapy,
      without a maximum time limit. Patients are assessed at baseline and subsequently
      every 6 months up to 36 months after the start of treatment. The primary outcome
      measure is the frequency and severity of manifestations of borderline personality
      disorder as assessed by the Borderline Personality Disorder Severity Index.
      Secondary outcome measures include parasuicidal behaviour, symptomatic distress,
      social and interpersonal functioning, personality functioning, attachment,
      capacity for mentalizing and quality of life. Cost-effectiveness is assessed in
      terms of the cost per quality-adjusted life year. Outcomes will be analyzed using
      multilevel analyses based on intention-to-treat principles. DISCUSSION: Severe
      borderline personality disorder is a serious psychological disorder that is
      associated with high burden. This multi-site randomized trial will provide
      further data concerning the efficacy and cost-effectiveness of MBT-DH for these
      patients. TRIAL REGISTRATION: NTR2175.

PMID- 24886403
TI  - Myocardial fibrosis in Eisenmenger syndrome: a descriptive cohort study exploring
      associations of late gadolinium enhancement with clinical status and survival.
AB  - BACKGROUND: A relationship between myocardial fibrosis and ventricular
      dysfunction has been demonstrated using late gadolinium enhancement (LGE) in the
      pressure-loaded right ventricle from congenital heart defects. In patients with
      Eisenmenger syndrome (ES), the presence of LGE has not been investigated. The
      aims of this study were to detect any myocardial fibrosis in ES and describe
      major clinical variables associated with the finding. METHODS: From 45 subjects
      screened, 30 subjects (age 43 +/- 13 years, 20 female) underwent prospective
      cardiovascular magnetic resonance with LGE to quantify biventricular volume and
      function as well as maximal and submaximal exercise during a single visit.
      Standard cine acquisitions were obtained for ventricular volume and function.
      Further imaging was performed after administration of 0.1 mmol/kg gadolinium
      contrast. Regions of LGE were evaluated qualitatively and quantitatively by
      manual contouring of identified areas, with total area expressed as a percentage
      of mass. Patients were followed prospectively (mean follow up 7.4 +/- 0.4 years)
      and any deaths recorded. Patients with LGE findings were compared to those
      without. RESULTS: LGE was present in 22/30 (73%) patients, specifically in RV
      myocardium (70%), RV trabeculae (60%), LV myocardium (33%) or LV papillary
      muscles (30%), though in small amounts (mean 1.4% of total ventricular mass,
      range 0.16 - 6.0%). Those with any LGE were not different in age, history of
      arrhythmia, desaturation, nor hemoglobin, nor ventricular size, mass, or
      function. Exercise capacity was low, but also not different between those with
      and without LGE. Similarly no significant associations were found with amount of
      fibrosis. There were five deaths among patients with LGE, versus two in patients
      without, but no difference in survival (log rank =0.03, P = 0.85). CONCLUSIONS:
      Myocardial fibrosis by LGE is common in ES, though not extensive. The presence
      and quantity of LGE did not correlate with ventricular size, function, degree of
      cyanosis, exercise capacity, or survival in this pilot study. More data are
      clearly required before recommendations for routine use of LGE in these patients
      can be made.

PMID- 24886404
TI  - Thrombomodulin expression regulates tumorigenesis in bladder cancer.
AB  - BACKGROUND: The identification of potential tumor markers will help improve
      therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive
      urothelial marker. TM was reported to be one of the endogenous anti-metastatic
      factors and has diagnostic and prognostic values for the progression of
      carcinoma. In the present study, we examine the role of TM in bladder cancer.
      METHODS: We studied the role of TM in tumor behavior and related signaling
      pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82
      and T24, and in vivo using animal models. We also selected clinical specimens
      from 100 patients with bladder cancer for immunohistochemical staining to
      evaluate the predictive capacity of TM in tumor invasiveness. RESULTS: The data
      revealed that positive immunoreactivity for TM was inversely correlated with
      clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM
      expression could predict the aggressive tumor growth and advanced clinical stage
      in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability
      were augmented in vitro and in vivo. The underlying changes included increased
      cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and
      angiogenesis. Moreover, inhibition of NF-kappaB activation significantly
      increased TM expression and attenuated tumor aggressiveness in bladder cancer.
      CONCLUSIONS: TM plays an important role in bladder cancer tumor aggressiveness in
      vitro and in vivo and is a clinically significant predictor that may represent a
      suitable therapeutic target for bladder cancer.

PMID- 24886405
TI  - Berberine inhibits the expression of hypoxia induction factor-1alpha and
      increases the radiosensitivity of prostate cancer.
AB  - BACKGROUND: The radiation resistance of prostate cancer remains the primary
      obstacle to improve patient survival. This study aimed to investigate the effects
      of berberine, a commonly used natural product, on the radiosensitivity of
      prostate cancer. METHODS: Prostate cancer cell line LNCaP and DU-145 were
      subjected to hypoxia and/or ionizing radiation (IR), in the presence or absence
      of berberine treatment. Cell growth and colony formation, and apoptosis were
      evaluated. Moreover, LNCaP cells were xenografted into nude mice and subjected to
      IR and/or berberine treatment. The expression of HIF-1alpha and VEGF in prostate
      cancer cells and xenografts was detected by Western blot analysis. RESULTS:
      Berberine increased radiosensitivity of prostate cancer cells and xenografts in a
      dose dependent manner, and this was correlated with the inhibition of HIF-1alpha
      and VEGF expression. CONCLUSIONS: Berberine may inhibit the expression of HIF
      1alpha and VEGF and thus confer radiosensitivity on prostatic cancer cells.
      Berberine has potential application as an adjuvant in radiotherapy of prostatic
      cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1519827543125021.

PMID- 24886407
TI  - Excitation-contraction coupling properties in women with work-related myalgia: a
      preliminary study.
AB  - We investigated the potential role of selected excitation-contraction coupling
      processes in females with work-related myalgia (WRM) by comparing WRM with
      healthy controls (CON) using tissue from extensor carpi radialis brevis (ECRB)
      and trapezius (TRAP) muscles. For the ECRB, age (mean +/- SE) was 29.6 +/- 3.5
      years for CON (n = 9) and 39.2 +/- 2.8 years for WRM (n = 13), while for the
      TRAP, the values were 26.0 +/- 2.1 years for CON (n = 7) and 44.6 +/- 2.9 years
      for WRM (n = 11). For the sarcoplasmic reticulum (SR) of the ECRB, WRM displayed
      concentrations (nmol.(mg protein)(-1).min(-1)) that were lower (P < 0.05) for
      Total (202 +/- 4.4 vs 178 +/- 7.1), Basal (34 +/- 1.6 vs 30.1 +/- 1.3), and
      maximal Ca(2+)-ATPase activity (Vmax, 168 +/- 4.9 vs 149 +/- 6.3), and Ca(2+)
      uptake (5.06 +/- 0.31 vs 4.13 +/- 0.29), but not SERCA1a and SERCA2a isoforms, by
      comparison with CON. When age was incorporated as a co-variant, Total, Basal, and
      Ca(2+)-uptake remained different from CON (P < 0.05), but not Vmax (P = 0.13).
      For TRAP, none of the ATPase properties differed between groups (P > 0.05) either
      before or following adjustment for age. No differences (P > 0.05) were observed
      between the groups for Ca(2+)-release in the SR for either TRAP or ECRB.
      Similarly, no deficiencies, regardless of muscle, were noted for either the Na(+)
      K(+)-ATPase content or the alpha and beta subunit isoform distribution in WRM.
      This preliminary study provides a basis for further research, with expanded
      numbers, investigating the hypothesis that abnormalities in SR Ca(2+)-regulation
      are involved in the cellular etiology of WRM. 

PMID- 24886406
TI  - Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible
      involvement of glial cells.
AB  - BACKGROUND: The participation of spinal P2X receptors in neuropathic pain is well
      recognized. However, the role of P2Y receptors has been less studied. The purpose
      of this study was to investigate the contribution of spinal P2Y6,11 receptors
      following peripheral nerve damage induced by spinal nerve ligation. In addition,
      we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in
      presence of the selective P2Y6,11 receptors antagonists. Furthermore, we
      evaluated the participation of spinal microglia and astrocytes in the
      pronociceptive role of P2Y6,11 receptors. RESULTS: Spinal administration of the
      selective P2Y6 (MRS2578, 10-100 MUM) and P2Y11 (NF340, 0.3-30 MUM) receptor
      antagonists reduced tactile allodynia in spinal nerve ligated rats. Nerve injury
      increased the expression of P2Y6,11 receptors at 7, 14 and 21 days after injury.
      Furthermore, intrathecal administration of MRS2578 (100 MUM/day) and NF340 (30
      MUM/day) for 3 days significantly reduced spinal nerve injury-induced increase in
      P2Y6,11 receptors expression, respectively. Spinal treatment (on day 14 after
      injury) with minocycline (100 MUg/day) or fluorocitrate (1 nmol/day) for 7 days
      reduced tactile allodynia and spinal nerve injury-induced up-regulation in Iba-1
      and GFAP, respectively. In addition, minocycline reduced nerve injury-induced up
      regulation in P2Y6,11 receptors whereas that fluorocitrate diminished P2Y11, but
      not P2Y6, receptors up-regulation. Intrathecal treatment (on day 21 after injury)
      with the selective P2Y6 (PSB0474, 3-30 MUM) and P2Y11 (NF546, 1-10 MUM) receptor
      agonists produced remarkable tactile allodynia in nerve ligated rats previously
      treated with minocycline or fluorocitrate for 7 days. CONCLUSIONS: Our data
      suggest that spinal P2Y6 is present in spinal microglia while P2Y11 receptors are
      present in both spinal microglia and astrocytes, and both receptors are up
      regulated in rats subjected to spinal nerve injury. In addition, our data suggest
      that the spinal P2Y6 and P2Y11 receptors participate in the maintenance of
      neuropathic pain.

PMID- 24886408
TI  - On-farm biosecurity as perceived by professionals visiting Swedish farms.
AB  - BACKGROUND: On-farm biosecurity is an important part of disease prevention and
      control, this applies to live animal contacts as well as indirect contacts e.g.
      via professionals visiting farms in their work. The objectives of this study were
      to investigate how professionals visiting animal farms in Sweden in their daily
      work perceive the on-farm conditions for biosecurity, the factors that influence
      their own biosecurity routines and what they describe as obstacles for
      biosecurity. Suggestions for improvements were also asked for. Questionnaires
      were distributed to professionals visiting farms in their daily work;
      veterinarians, livestock hauliers, artificial insemination technicians, animal
      welfare inspectors and cattle hoof trimmers. The sample was a convenience sample,
      based on accessibility to registers or collaboration with organisations
      distributing the questionnaire. Respondents were asked about the availability of
      certain biosecurity conditions related to farm visits, e.g. if facilities for
      hand washing were available, how important different factors were for their own
      routines and, through open ended questions, to describe obstacles and suggestions
      for improvement. RESULTS: After data cleaning, there were responses from 368
      persons. There was a difference in the proportion of visited farms reported to
      have certain biosecurity measures in place related to animal species present on
      the farm. In general, visited pig farms had a higher proportion of biosecurity
      measures in place, whereas the conditions were poorer on sheep and goat farms and
      horse farms. There were also differences between the visitor categories; the
      perceived conditions for biosecurity varied between the groups, e.g. livestock
      hauliers did not have access to hand washing facilities as often as veterinarians
      did. In all groups, a majority of the respondents perceived obstacles for on-farm
      biosecurity, among veterinarians 66% perceived that there were obstacles. Many of
      the reported obstacles related to the very basics of biosecurity, such as access
      to soap and water. Responsibility was identified to be a key issue; while some
      farmers expect visitors to take responsibility for keeping up biosecurity they do
      not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents
      reported obstacles for keeping good biosecurity related to on-farm conditions.
      There was a gap when it came to responsibility which needs to be clarified.
      Visitors need to take responsibility for avoiding spread of disease, while
      farmers need to assume responsibility for providing adequate conditions for on
      farm biosecurity.

PMID- 24886409
TI  - Effect of two dietary fibers on satiety and glycemic parameters: a randomized,
      double-blind, placebo-controlled, exploratory study.
AB  - BACKGROUND: Dietary carbohydrates may affect metabolic and physiologic
      parameters. The present study evaluated whether a combination of two dietary
      fibers, oligofructose (OFS) and pectin (P), altered satiety and glycemic
      parameters. The primary objective of this study was to determine whether dietary
      supplementation for 3 weeks with OFS + P would produce a greater reduction in
      energy intake of an ad libitum test meal compared to control. METHODS: This was a
      single center, randomized, double-blind, placebo-controlled, parallel group study
      in overweight and obese, otherwise healthy, subjects (N = 96). There were two OFS
      + P treatment groups: high-dose (30 g/d), low-dose (15 g/d), and a control group
      (maltodextrin 15 g/d). Energy intake, appetite measures based on Satiety Labeled
      Intensity Magnitude (SLIM) scale, fasting and post-prandial glucose, and insulin
      levels and body weight were measured at baseline and at the end of 3 weeks.
      Adverse events and gastrointestinal tolerability of the treatments were also
      assessed. RESULTS: An analysis of covariance (ANCOVA) performed on the primary
      endpoint change from baseline in energy intake, showed no statistically
      significant difference in energy intake among the three treatment groups (p =
      0.5387). The LS mean changes (SE) in energy intake from baseline to week 3 were 
      58.3 (42.4) kilocalories (kcal) for the high dose group, -74.2 (43.6) kcal for
      the low dose group, and -9.0 (42.9) kcal for the control group. For the pairwise
      comparisons of OFS + P doses and control, confidence intervals were constructed
      around the difference in LS mean changes. All study products were generally well
      tolerated. CONCLUSION: There was a directional benefit in ad libitum energy
      intake for both OFS + P doses compared to control, with a greater reduction in
      kilocalories in the low dose comparison, but the reductions were not significant.
      Further studies are warranted. CLINICAL TRIAL REGISTRATION: GSK Clinical Study
      Register # W7781293.

PMID- 24886410
TI  - Combination of uniform design with artificial neural network coupling genetic
      algorithm: an effective way to obtain high yield of biomass and algicidal
      compound of a novel HABs control actinomycete.
AB  - Controlling harmful algae blooms (HABs) using microbial algicides is cheap,
      efficient and environmental-friendly. However, obtaining high yield of algicidal
      microbes to meet the need of field test is still a big challenge since
      qualitative and quantitative analysis of algicidal compounds is difficult. In
      this study, we developed a protocol to increase the yield of both biomass and
      algicidal compound present in a novel algicidal actinomycete Streptomyces
      alboflavus RPS, which kills Phaeocystis globosa. To overcome the problem in
      algicidal compound quantification, we chose algicidal ratio as the index and used
      artificial neural network to fit the data, which was appropriate for this
      nonlinear situation. In this protocol, we firstly determined five main
      influencing factors through single factor experiments and generated the
      multifactorial experimental groups with a U15(155) uniform-design-table. Then, we
      used the traditional quadratic polynomial stepwise regression model and an
      accurate, fully optimized BP-neural network to simulate the fermentation.
      Optimized with genetic algorithm and verified using experiments, we successfully
      increased the algicidal ratio of the fermentation broth by 16.90% and the dry
      mycelial weight by 69.27%. These results suggested that this newly developed
      approach is a viable and easy way to optimize the fermentation conditions for
      algicidal microorganisms. 

PMID- 24886411
TI  - Comparison of next-generation sequencing samples using compression-based
      distances and its application to phylogenetic reconstruction.
AB  - BACKGROUND: Enormous volumes of short read data from next-generation sequencing
      (NGS) technologies have posed new challenges to the area of genomic sequence
      comparison. The multiple sequence alignment approach is hardly applicable to NGS
      data due to the challenging problem of short read assembly. Thus alignment-free
      methods are needed for the comparison of NGS samples of short reads. RESULTS:
      Recently several k-mer based distance measures such as CVTree, d2(S), and co
      phylog have been proposed or enhanced to address this problem. However, how to
      choose an optimal k value for those distance measures is not trivial since it may
      depend on different aspects of the sequence data. In this paper, we considered an
      alternative parameter-free approach: compression-based distance measures. These
      measures have shown good performance for the comparison of long genomic
      sequences, but they have not yet been tested on NGS short reads. Hence, we
      performed extensive validation in this study and showed that the compression
      based distances are highly consistent with those distances obtained from the k
      mer based methods, from the multiple sequence alignment approach, and from
      existing benchmarks in the literature. Moreover, as the compression-based
      distance measures are parameter-free, no parameter optimization is required and
      these measures still perform consistently well on multiple types of sequence
      data, for different kinds of species and taxonomy levels. CONCLUSIONS: The
      compression-based distance measures are assembly-free, alignment-free, parameter
      free, and thus represent useful tools for the comparison of long genomic
      sequences as well as the comparison of NGS samples of short reads.

PMID- 24886412
TI  - Expression and characterization of a GH43 endo-arabinanase from Thermotoga
      thermarum.
AB  - BACKGROUND: Arabinan is an important plant polysaccharide degraded mainly by two
      hydrolytic enzymes, endo-arabinanase and alpha-L-arabinofuranosidase. In this
      study, the characterization and application in arabinan degradation of an endo
      arabinanase from Thermotoga thermarum were investigated. RESULTS: The recombinant
      endo-arabinanase was expressed in Escherichia coli BL21 (DE3) and purified by
      heat treatment followed by purification on a nickel affinity column
      chromatography. The purified endo-arabinanase exhibited optimal activity at pH
      6.5 and 75 degrees C and its residual activity retained more than 80% of its
      initial activity after being incubated at 80 degrees C for 2 h. The results
      showed that the endo-arabinanase was very effective for arabinan degradation at
      higher temperature. When linear arabinan was used as the substrate, the apparent
      K(m) and V(max) values were determined to be 12.3 +/- 0.15 mg ml-1 and 1,052.1 +/
      12.7 MUmol ml-1 min-1, respectively (at pH 6.5, 75 degrees C), and the
      calculated kcat value was 349.3 +/- 4.2 s-1. CONCLUSIONS: This work provides a
      useful endo-arabinanase with high thermostability andcatalytic efficiency, and
      these characteristics exhibit a great potential for enzymatic conversion of
      arabinan.

PMID- 24886413
TI  - No increase in new users of blood glucose-lowering drugs in Norway 2006-2011: a
      nationwide prescription database study.
AB  - BACKGROUND: National estimates for the occurrence of diabetes are difficult to
      obtain, particularly time trends in incidence. The aim was to describe time
      trends in prevalent and incident use of blood glucose-lowering drugs by age group
      and gender in Norway during 2005-2011. METHODS: Data were obtained from the
      nationwide Norwegian Prescription Database. We defined prevalent users of
      "insulins only" as individuals having no oral antidiabetic drugs (OAD) dispensed
      from a pharmacy during the previous 24 months or in the subsequent 12 months.
      Incident users had no blood glucose-lowering drugs dispensed in the previous 24
      months; incident "insulins only" users also had no OAD in the subsequent 12
      months. RESULTS: In 2011, 3.2% of the population had blood glucose-lowering drugs
      dispensed, and the incidence rate was 313 per 100,000 person years. The
      prevalence of OAD use increased from 1.8% in 2005 to 2.4% in 2011; however a
      decreasing trend in incidence of OAD use was observed, particularly in those aged
      70 years and older. In 2010, 0.64% of the population had insulins only dispensed,
      with an overall incidence rate in the total population of 33 per 100,000 person
      years which was stable over time. CONCLUSIONS: In this nationwide study, we found
      that although the prevalent use of OAD had increased in recent years, incident
      use was stable or had decreased. This may indicate that the increase in diabetes
      occurrence in Norway is levelling off, at least temporarily.

PMID- 24886414
TI  - Food price policies improve diet quality while increasing socioeconomic
      inequalities in nutrition.
AB  - BACKGROUND: Prices are an important determinant of food choices. Consequently,
      food price policies (subsidies and/or taxes) are proposed to improve the
      nutritional quality of diets. The aim of the present study was to explore the
      impact of food price policies on the expenditures and nutritional quality of the
      food baskets chosen by low- and medium-income households. METHODS: Experimental
      economics was used to examine two price manipulations: i) a fruit and vegetable
      price subsidy named "fruit and vegetables condition"; ii) a healthy-product
      subsidy coupled with an unhealthy-product tax named "nutrient profile condition".
      The nutrient profiling system called SAIN,LIM was used. This system classifies
      each individual food according to its overall nutritional quality which then
      allows for a food item to be taxed or subsidized. Women from low- (n = 95) and
      medium-incomes (n = 33) selected a daily food basket, first, at current prices
      and then at manipulated prices. The redistributive effects of experimental
      conditions were assessed by comparing the extent of savings induced by subsidies
      and of costs generated by the tax on the two income groups. Energy density
      (kcal/100 g), free sugars (% energy) and the mean adequacy ratio (MAR) were used
      as nutritional quality indicators. RESULTS: At baseline (before price
      manipulations), low-income women selected less expensive and less healthy baskets
      than medium-income ones. After price manipulations expenditures for both income
      group decreased significantly, whereas, the nutritional quality improved (energy
      density decreased, the MAR increased). Additionally, the redistributive effects
      were less favourable for low-income women and their nutritional quality
      improvements from baseline were significantly lower. CONCLUSION: Low-income women
      derived fewer financial and nutritional benefits from implemented food subsidies
      and taxes than medium-income women. This outcome suggests that food price
      policies may improve diet quality while increasing socio-economic inequalities in
      nutrition.

PMID- 24886415
TI  - A detailed staging scheme for late larval development in Strongylocentrotus
      purpuratus focused on readily-visible juvenile structures within the rudiment.
AB  - BACKGROUND: The purple sea urchin, Strongylocentrotus purpuratus, has long been
      the focus of developmental and ecological studies, and its recently-sequenced
      genome has spawned a diversity of functional genomics approaches. S. purpuratus
      has an indirect developmental mode with a pluteus larva that transforms after 1-3
      months in the plankton into a juvenile urchin. Compared to insects and frogs,
      mechanisms underlying the correspondingly dramatic metamorphosis in sea urchins
      remain poorly understood. In order to take advantage of modern techniques to
      further our understanding of juvenile morphogenesis, organ formation,
      metamorphosis and the evolution of the pentameral sea urchin body plan, it is
      critical to assess developmental progression and rate during the late larval
      phase. This requires a staging scheme that describes developmental landmarks that
      can quickly and consistently be used to identify the stage of individual living
      larvae, and can be tracked during the final two weeks of larval development, as
      the juvenile is forming. RESULTS: Notable structures that are easily observable
      in developing urchin larvae are the developing spines, test and tube feet within
      the juvenile rudiment that constitute much of the oral portion of the adult body
      plan. Here we present a detailed staging scheme of rudiment development in the
      purple urchin using soft structures of the rudiment and the primordia of these
      juvenile skeletal elements. We provide evidence that this scheme is robust and
      applicable across a range of temperature and feeding regimes. CONCLUSIONS: Our
      proposed staging scheme provides both a useful method to study late larval
      development in the purple urchin, and a framework for developing similar staging
      schemes across echinoderms. Such efforts will have a high impact on evolutionary
      developmental studies and larval ecology, and facilitate research on this
      important deuterostome group.

PMID- 24886416
TI  - Functional properties of the HIV-1 long terminal repeat containing single
      nucleotide polymorphisms in Sp site III and CCAAT/enhancer binding protein site
      I.
AB  - BACKGROUND: HIV-1 gene expression is driven by the long terminal repeat (LTR),
      which contains many binding sites shown to interact with an array of host and
      viral factors. Selective pressures within the host as well as the low fidelity of
      reverse transcriptase lead to changes in the relative prevalence of genetic
      variants within the HIV-1 genome, including the LTR, resulting in viral
      quasispecies that can be differentially regulated and can potentially establish
      niches within specific cell types and tissues. METHODS: Utilizing flow cytometry
      and electromobility shift assays, specific single-nucleotide sequence
      polymorphisms (SNPs) were shown to alter both the phenotype of LTR-driven
      transcription and reactivation. Additional studies also demonstrated differential
      loading of transcription factors to probes derived from the double-variant LTR as
      compared to probes from the wild type. RESULTS: This study has identified
      specific SNPs within CCAAT/enhancer binding protein (C/EBP) site I and Sp site
      III (3 T, C-to-T change at position 3, and 5 T, C-to-T change at position 5 of
      the binding site, respectively) that alter LTR-driven gene transcription and may
      alter the course of viral latency and reactivation. The HIV-1 LAI LTRs containing
      the SNPs of interest were coupled to a plasmid encoding green fluorescent protein
      (GFP), and polyclonal HIV-1 LTR-GFP stable cell lines utilizing bone marrow
      progenitor, T, and monocytic cell lines were constructed and utilized to explore
      the LTR phenotype associated with these genotypic changes. CONCLUSIONS: Although
      the 3 T and 5 T SNPs have been shown to be low-affinity binding sites, the fact
      that they can still result in effective HIV-1 LTR-driven gene expression,
      particularly within the TF-1 cell line, has suggested that the low binding site
      affinities associated with the 3 T C/EBP site I and 5 T Sp site III are
      potentially compensated for by the interaction of nuclear factor-kappaB with its
      corresponding binding sites under selected physiological and cellular conditions.
      Additionally, tumor necrosis factor-alpha and Tat can enhance basal transcription
      of each SNP-specific HIV-1 LTR; however, differential regulation of the LTR is
      both SNP- and cell type-specific.

PMID- 24886418
TI  - Thoracoscopic plication for a huge thoracic meningocele in a patient with
      neurofibromatosis.
AB  - Intrathoracic meningoceles associated with neurofibromatosis type I are rare, and
      the optimal treatment is still unknown. Herein, we present the case of a 48-year
      old Asian female with a huge thoracic meningocele associated with cutaneous
      neurofibromatosis type I and kyphoscoliosis of the thoracic spine. The large
      thoracic meningocele was successfully treated through thoracoscopic plication. 

PMID- 24886417
TI  - Agrobacterium-derived cytokinin influences plastid morphology and starch
      accumulation in Nicotiana benthamiana during transient assays.
AB  - BACKGROUND: Agrobacterium tumefaciens-based transient assays have become a common
      tool for answering questions related to protein localization and gene expression
      in a cellular context. The use of these assays assumes that the transiently
      transformed cells are observed under relatively authentic physiological
      conditions and maintain 'normal' sub-cellular behaviour. Although this premise is
      widely accepted, the question of whether cellular organization and organelle
      morphology is altered in Agrobacterium-infiltrated cells has not been examined in
      detail. The first indications of an altered sub-cellular environment came from
      our observation that a common laboratory strain, GV3101(pMP90), caused a drastic
      increase in stromule frequency. Stromules, or 'stroma-filled-tubules' emanate
      from the surface of plastids and are sensitive to a variety of biotic and abiotic
      stresses. Starting from this observation, the goal of our experiments was to
      further characterize the changes to the cell resulting from short-term bacterial
      infestation, and to identify the factor responsible for eliciting these changes.
      RESULTS: Using a protocol typical of transient assays we evaluated the impact of
      GV3101(pMP90) infiltration on chloroplast behaviour and morphology in Nicotiana
      benthamiana. Our experiments confirmed that GV3101(pMP90) consistently induces
      stromules and alters plastid position relative to the nucleus. These effects were
      found to be the result of strain-dependant secretion of cytokinin and its
      accumulation in the plant tissue. Bacterial production of the hormone was found
      to be dependant on the presence of a trans-zeatin synthase gene (tzs) located on
      the Ti plasmid of GV3101(pMP90). Bacteria-derived cytokinins were also correlated
      with changes to both soluble sugar level and starch accumulation. CONCLUSION:
      Although we have chosen to focus on how transient Agrobacterium infestation
      alters plastid based parameters, these changes to the morphology and position of
      a single organelle, combined with the measured increases in sugar and starch
      content, suggest global changes to cell physiology. This indicates that cells
      visualized during transient assays may not be as 'normal' as was previously
      assumed. Our results suggest that the impact of the bacteria can be minimized by
      choosing Agrobacterium strains devoid of the tzs gene, but that the alterations
      to sub-cellular organization and cell carbohydrate status cannot be completely
      avoided using this strategy.

PMID- 24886420
TI  - Challenges in software applications for the cognitive evaluation and stimulation
      of the elderly.
AB  - BACKGROUND: Computer-based cognitive stimulation applications can help the
      elderly maintain and improve their cognitive skills. In this research paper, our
      objectives are to verify the usability of PESCO (an open-software application for
      cognitive evaluation and stimulation) and to determine the concurrent validity of
      cognitive assessment tests and the effectiveness of PESCO's cognitive stimulation
      exercises. METHODS: Two studies were conducted in various community computer
      centers in the province of Granada. The first study tested tool usability by
      observing 43 elderly people and considering their responses to a questionnaire.
      In the second study, 36 elderly people completed pen-and-paper and PESCO tests
      followed by nine cognitive stimulation sessions. Meanwhile, a control group with
      34 participants used computers for nine non-structured sessions. RESULTS:
      Analysis of the first study revealed that although PESCO had been developed by
      taking usability guidelines into account, there was room for improvement. Results
      from the second study indicated moderate concurrent validity between PESCO and
      standardized tests (Pearson's r from .501 to .702) and highlighted the
      effectiveness of training exercises for improving attention (F = -4.111, p <
      .001) and planning (F = 5.791, p < .001) functions. CONCLUSIONS: PESCO can be
      used by the elderly. The PESCO cognitive test module demonstrated its concurrent
      validity with traditional cognitive evaluation tests. The stimulation module is
      effective for improving attention and planning skills.

PMID- 24886419
TI  - Heat shock protein 60: an endogenous inducer of dopaminergic cell death in
      Parkinson disease.
AB  - BACKGROUND: Increasing evidence suggests that inflammation associated with
      microglial cell activation in the substantia nigra (SN) of patients with
      Parkinson disease (PD) is not only a consequence of neuronal degeneration, but
      may actively sustain dopaminergic (DA) cell loss over time. We aimed to study
      whether the intracellular chaperone heat shock protein 60 (Hsp60) could serve as
      a signal of CNS injury for activation of microglial cells. METHODS: Hsp60 mRNA
      expression in the mesencephalon and the striatum of C57/BL6 mice treated with
      MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and the Hsp60/TH mRNA ratios
      in the SN of PD patients and aged-matched subjects were measured. To further
      investigate a possible link between the neuronal Hsp60 response and PD-related
      cellular stress, Hsp60 immunoblot analysis and quantification in cell lysates
      from SH-SY5Y after treatment with 100 MUM MPP+ (1-methyl-4-phenylpyridinium) at
      different time points (6, 12, 24 and 48 hours) compared to control cells were
      performed. Additional MTT and LDH assay were used. We next addressed the question
      as to whether Hsp60 influences the survival of TH+ neurons in mesencephalic
      neuron-glia cultures treated either with MPP+ (1 MUM), hHsp60 (10 MUg/ml) or a
      combination of both. Finally, we measured IL-1beta, IL-6, TNF-alpha and NO
      release by ELISA in primary microglial cell cultures following treatment with
      different hHsp60 preparations. Control cultures were exposed to LPS. RESULTS: In
      the mesencephalon and striatum of mice treated with MPTP and also in the SN of PD
      patients, we found that Hsp60 mRNA was up-regulated. MPP+, the active metabolite
      of MPTP, also caused an increased expression and release of Hsp60 in the human
      dopaminergic cell line SH-SY5Y. Interestingly, in addition to being toxic to DA
      neurons in primary mesencephalic cultures, exogenous Hsp60 aggravated the effects
      of MPP+. Yet, although we demonstrated that Hsp60 specifically binds to
      microglial cells, it failed to stimulate the production of pro-inflammatory
      cytokines or NO by these cells. CONCLUSIONS: Overall, our data suggest that Hsp60
      is likely to participate in DA cell death in PD but via a mechanism unrelated to
      cytokine release.

PMID- 24886421
TI  - Hepatitis B virus X protein accelerates hepatocarcinogenesis with partner
      survivin through modulating miR-520b and HBXIP.
AB  - BACKGROUND: Hepatitis B virus X protein (HBx) plays crucial roles in
      hepatocarcinogenesis. However, the underlying mechanism remains elusive. We have
      reported that HBx is able to up-regulate survivin in hepatocellular carcinoma
      tissues. The oncopreotein hepatitis B X-interacting protein (HBXIP), a target of
      miR-520b, is involved in the development of cancer. In this study, we focus on
      the investigation of hepatocarcinogenesis mediated by HBx. METHODS: The
      expression of HBx and survivin was examined in the liver tissues of HBx-Tg mice.
      The effect of HBx/survivin on the growth of LO2-X-S cells was determined by
      colony formation and transplantation in nude mice. The effect of HBx/survivin on
      promoter of miR-520b was determined by Western blot analysis, luciferase reporter
      gene assay, co-immunoprecipitation (co-IP) and chromatin immunoprecipitation
      (ChIP), respectively. The expression of HBx, survivin and HBXIP was detected by
      immunohistochemistry and real-time PCR in clinical HCC tissues, respectively. The
      DNA demethylation of HBXIP promoter was examined. The functional influence of miR
      520b and HBXIP on proliferation of hepatoma cells was analyzed by MTT, colony
      formation, EdU and transplantation in nude mice in vitro and in vivo. RESULTS: In
      this study, we provided evidence that HBx up-regulated survivin in the liver
      cancer tissues of HBx-Tg mice aged 18 M. The engineered LO2 cell lines with
      survivin and/or HBx were successfully established, termed LO2-X-S. MiR-520b was
      down-regulated in LO2-X-S cells and clinical HCC tissues. Our data revealed that
      HBx survivin-dependently down-regulated miR-520b through interacting with Sp1 in
      the cells. HBXIP was highly expressed in LO2-X-S cells, liver cancer tissues of
      HBx-Tg mice aged 18 M and clinical HCC tissues (75.17%, 112/149). The expression
      level of HBXIP was positively associated with those of HBx or survivin in
      clinical HCC tissues. In addition, we showed that HBx survivin-dependently up
      regulated HBXIP through inducing demethylation of HBXIP promoter in LO2-X-S cells
      and clinical HCC tissues. In function, low level miR-520b and high level HBXIP
      mediated by HBx with partner survivin contributed to the growth of LO2-X-S cells
      in vitro and in vivo. CONCLUSION: HBx accelerates hepatocarcinogenesis with
      partner survivin through modulating tumor suppressor miR-520b and oncoprotein
      HBXIP.

PMID- 24886422
TI  - Usefulness of the heart-rate variability complex for predicting cardiac mortality
      after acute myocardial infarction.
AB  - BACKGROUND: Previous studies indicate that decreased heart-rate variability (HRV)
      is related to the risk of death in patients after acute myocardial infarction
      (AMI). However, the conventional indices of HRV have poor predictive value for
      mortality. Our aim was to develop novel predictive models based on support vector
      machine (SVM) to study the integrated features of HRV for improving risk
      stratification after AMI. METHODS: A series of heart-rate dynamic parameters from
      208 patients were analyzed after a mean follow-up time of 28 months. Patient
      electrocardiographic data were classified as either survivals or cardiac deaths.
      SVM models were established based on different combinations of heart-rate dynamic
      variables and compared to left ventricular ejection fraction (LVEF), standard
      deviation of normal-to-normal intervals (SDNN) and deceleration capacity (DC) of
      heart rate. We tested the accuracy of predictors by assessing the area under the
      receiver-operator characteristics curve (AUC). RESULTS: We evaluated a SVM
      algorithm that integrated various electrocardiographic features based on three
      models: (A) HRV complex; (B) 6 dimension vector; and (C) 8 dimension vector. Mean
      AUC of HRV complex was 0.8902, 0.8880 for 6 dimension vector and 0.8579 for 8
      dimension vector, compared with 0.7424 for LVEF, 0.7932 for SDNN and 0.7399 for
      DC. CONCLUSIONS: HRV complex yielded the largest AUC and is the best classifier
      for predicting cardiac death after AMI.

PMID- 24886423
TI  - Solitary splenic metastasis of ovarian carcinoma: a case report.
AB  - INTRODUCTION: Splenic metastasis from ovarian carcinoma generally presents as
      peritoneal spread with multiorgan involvement. Fewer than 30 cases of solitary
      parenchymal splenic metastasis from ovarian carcinoma have been published in the
      literature. The presentation is often asymptomatic. CASE PRESENTATION: An
      increase in tumor marker CA-125 from 18.1 to 132.6 units/ml (normal < 35
      units/ml) was measured in a 56-year-old Israeli Jewish woman who had undergone,
      six years previously, a total abdominal hysterectomy with bilateral salpingo
      oophorectomy due to right ovarian carcinoma. An abdominal computed tomography
      scan revealed a mass of 6 * 8 cm at the anterior of the spleen, with close
      proximity to the wall of the stomach. A gastroscopy demonstrated exterior
      pressure on the stomach body. An open splenectomy was performed to exclude a
      peritoneal carcinomatosis. No intraoperative evidence of tumoral spreading in the
      abdominal cavity was observed, other than the spleen. The final histologic result
      demonstrated a high-grade carcinoma consistent with metastatic endometrioid-type
      ovarian carcinoma grade 3. CONCLUSIONS: This case highlights the importance of
      cancer antigen 125 assessment and medical imaging in the follow-up of ovarian
      carcinoma. Open laparotomy, or laparoscopy, enables exclusion of a peritoneal
      carcinomatosis, which is more common than solitary parenchymal splenic
      metastasis, as was presented in the current case.

PMID- 24886424
TI  - Relationship between arsenic skin lesions and the age of natural menopause.
AB  - BACKGROUND: Chronic exposure to arsenic is associated with neoplastic,
      cardiovascular, endocrine, neuro-developmental disorders and can have an adverse
      effect on women's reproductive health outcomes. This study examined the
      relationship between arsenic skin lesions (a hallmark sign of chronic arsenic
      poisoning) and age of natural menopause (final menopausal period) in populations
      with high levels of arsenic exposure in Bangladesh. METHODS: We compared
      menopausal age in two groups of women--with and without arsenic skin lesions; and
      presence of arsenic skin lesions was used as an indicator for chronic arsenic
      exposure. In a cross-sectional study, a total of 210 participants were randomly
      identified from two ongoing studies--participants with arsenic skin lesions were
      identified from an ongoing clinical trial and participants with no arsenic skin
      lesions were identified from an ongoing cohort study. Mean age of menopause
      between these two groups were calculated and compared. Multivariable linear
      regression was used to estimate the relationship between the status of the
      arsenic skin lesions and age of natural menopause in women. RESULTS: Women with
      arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause
      compared to those without arsenic skin lesions. After adjusting with
      contraceptive use, body mass index, urinary arsenic level and family history of
      premature menopause, the difference between the groups' age at menopause was 2.1
      years earlier (p <0.001) for respondents with arsenic skin lesions. CONCLUSIONS:
      The study showed a statistically significant association between chronic exposure
      to arsenic and age at menopause. Heavily exposed women experienced menopause two
      years earlier than those with lower or no exposure.

PMID- 24886425
TI  - Effect of living area and sports club participation on physical fitness in
      children: a 4 year longitudinal study.
AB  - BACKGROUND: Cross-sectional studies detected associations between physical
      fitness, living area, and sports participation in children. Yet, their scientific
      value is limited because the identification of cause-and-effect relationships is
      not possible. In a longitudinal approach, we examined the effects of living area
      and sports club participation on physical fitness development in primary school
      children from classes 3 to 6. METHODS: One-hundred and seventy-two children (age:
      9-12 years; sex: 69 girls, 103 boys) were tested for their physical fitness
      (i.e., endurance [9-min run], speed [50-m sprint], lower- [triple hop] and upper
      extremity muscle strength [1-kg ball push], flexibility [stand-and-reach], and
      coordination [star coordination run]). Living area (i.e., urban or rural) and
      sports club participation were assessed using parent questionnaire. RESULTS: Over
      the 4 year study period, urban compared to rural children showed significantly
      better performance development for upper- (p = 0.009, ES = 0.16) and lower
      extremity strength (p < 0.001, ES = 0.22). Further, significantly better
      performance development were found for endurance (p = 0.08, ES = 0.19) and lower
      extremity strength (p = 0.024, ES = 0.23) for children continuously participating
      in sports clubs compared to their non-participating peers. CONCLUSIONS: Our
      findings suggest that sport club programs with appealing arrangements appear to
      represent a good means to promote physical fitness in children living in rural
      areas.

PMID- 24886426
TI  - Construction of an environmental quality index for public health research.
AB  - BACKGROUND: A more comprehensive estimate of environmental quality would improve
      our understanding of the relationship between environmental conditions and human
      health. An environmental quality index (EQI) for all counties in the U.S. was
      developed. METHODS: The EQI was developed in four parts: domain identification;
      data source acquisition; variable construction; and data reduction. Five
      environmental domains (air, water, land, built and sociodemographic) were
      recognized. Within each domain, data sources were identified; each was temporally
      (years 2000-2005) and geographically (county) restricted. Variables were
      constructed for each domain and assessed for missingness, collinearity, and
      normality. Domain-specific data reduction was accomplished using principal
      components analysis (PCA), resulting in domain-specific indices. Domain-specific
      indices were then combined into an overall EQI using PCA. In each PCA procedure,
      the first principal component was retained. Both domain-specific indices and
      overall EQI were stratified by four rural-urban continuum codes (RUCC). Higher
      values for each index were set to correspond to areas with poorer environmental
      quality. RESULTS: Concentrations of included variables differed across rural
      urban strata, as did within-domain variable loadings, and domain index loadings
      for the EQI. In general, higher values of the air and sociodemographic indices
      were found in the more metropolitan areas and the most thinly populated areas
      have the lowest values of each of the domain indices. The less-urbanized counties
      (RUCC 3) demonstrated the greatest heterogeneity and range of EQI scores (-4.76,
      3.57) while the thinly populated strata (RUCC 4) contained counties with the most
      positive scores (EQI score ranges from -5.86, 2.52). CONCLUSION: The EQI holds
      promise for improving our characterization of the overall environment for public
      health. The EQI describes the non-residential ambient county-level conditions to
      which residents are exposed and domain-specific EQI loadings indicate which of
      the environmental domains account for the largest portion of the variability in
      the EQI environment. The EQI was constructed for all counties in the United
      States, incorporating a variety of data to provide a broad picture of
      environmental conditions. We undertook a reproducible approach that primarily
      utilized publically-available data sources.

PMID- 24886427
TI  - Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal
      cancer patients than in healthy controls.
AB  - BACKGROUND: The association between alpha-1 antitrypsin (AAT) deficiency and
      colorectal cancer (CRC) is currently controversial. The present study compares
      AAT serum concentrations and gene frequencies between a group of CRC patients and
      a control group of healthy unrelated people (HUP). METHODS: 267 CRC subjects (63%
      males, 72 +/- 10 years old) were enlisted from a Hospital Clinic setting in
      Asturias, Spain. The HUP group comprised 327 subjects (67% males, mean age 70 +/-
      7.5 years old) from the same geographical region. Outcome measures were AAT serum
      concentrations measured by nephelometry, and AAT phenotyping characterization by
      isoelectric focusing. RESULTS: Significantly higher serum concentrations were
      found among CRC (208 +/- 60) than in HUP individuals (144 +/- 20.5) (p = 0.0001).
      No differences were found in the phenotypic distribution of the Pi*S and Pi*Z
      allelic frequencies (p = 0.639), although the frequency of Pi*Z was higher in CRC
      (21%) than in HUP subjects (15%). CONCLUSIONS: The only statistically significant
      finding in this study was the markedly higher AAT serum concentrations found in
      CRC subjects compared with HUP controls, irrespective of whether their Pi*
      phenotype was normal (Pi*MM) or deficient (Pi*MS, Pi*MZ and Pi*SZ). Although
      there was a trend towards the more deficient Pi* phenotype the more advanced the
      tumor, the results were inconclusive due to the small sample size. Consequently,
      more powerful studies are needed to reach firmer conclusions on this matter.

PMID- 24886429
TI  - The role of interpersonal communication in the process of knowledge mobilization
      within a community-based organization: a network analysis.
AB  - BACKGROUND: Diffusion of innovations theory has been widely used to explain
      knowledge mobilization of research findings. This theory posits that individuals
      who are more interpersonally connected within an organization may be more likely
      to adopt an innovation (e.g., research evidence) than individuals who are less
      interconnected. Research examining this tenet of diffusion of innovations theory
      in the knowledge mobilization literature is limited. The purpose of the present
      study was to use network analysis to examine the role of interpersonal
      communication in the adoption and mobilization of the physical activity
      guidelines for people with spinal cord injury (SCI) among staff in a community
      based organization (CBO). METHODS: The study used a cross-sectional, whole
      network design. In total, 56 staff completed the network survey. Adoption of the
      guidelines was assessed using Rogers' innovation-decision process and
      interpersonal communication was assessed using an online network instrument.
      RESULTS: The patterns of densities observed within the network were indicative of
      a core-periphery structure revealing that interpersonal communication was greater
      within the core than between the core and periphery and within the periphery.
      Membership in the core, as opposed to membership in the periphery, was associated
      with greater knowledge of the evidence-based physical activity resources
      available and engagement in physical activity promotion behaviours (ps < 0.05).
      Greater in-degree centrality was associated with adoption of evidence-based
      behaviours (p < 0.05). CONCLUSIONS: Findings suggest that interpersonal
      communication is associated with knowledge mobilization and highlight how the
      network structure could be improved for further dissemination efforts. KEYWORDS:
      diffusion of innovations; network analysis; community-based organization;
      knowledge mobilization; knowledge translation, interpersonal communication.

PMID- 24886430
TI  - Estimating a minimal clinically important difference for the EuroQol 5-Dimension
      health status index in persons with multiple sclerosis.
AB  - BACKGROUND: Limited data define what constitutes a minimal clinically important
      difference (MCID) on the EuroQol 5-Dimension (EQ-5D) health status index in
      persons with multiple sclerosis (PwMS). We sought to estimate the MCID for the EQ
      5D health index in North American PwMS. METHODS: PwMS completing the Patient
      Determined Disease Steps (PDDS) scale, 12-Item Multiple Sclerosis Walking Scale
      (MSWS-12) and EQ-5D as part of the North American Research Committee on Multiple
      Sclerosis (NARCOMS) registry's spring 2011 update and supplemental survey were
      included in this retrospective, cross-sectional study. Distribution-based
      (standard error of measurement [SEM], 0.50 standard deviation [SD] and 0.33 SD
      unit) approaches were used to estimate a range of MCIDs for the EQ-5D based upon
      disease severity groups determined by the PDDS and MSWS-12 tertiles. RESULTS: A
      total of 3,044 participants were included. Moderately strong correlations between
      the EQ-5D and the PDDS and MSWS-12 were observed (Spearman's r = -0.56 and -0.59,
      respectively, p < 0.0001 for both). MCID estimates based on PDDS score categories
      ranged from 0.065-0.158 (SEMs), 0.059-0.142 (0.50 SDs) and 0.039-0.095 (0.33
      SDs). MCID estimates as measured by MSWS-12 tertile categories ranged from 0.068
      0.098 (SEMs), 0.061-0.088 (0.50 SDs), and 0.041-0.059 (0.33 SDs). Across both the
      PDDS and tertiles of MSWS-12, MCID estimates tended to be larger as disease
      severity worsened. Mean weighted MCID estimates ranged from 0.05-0.084 for both
      the PDDS and MSWS-12 tertiles. CONCLUSION: MCID estimates for the EQ-5D in PwMS
      were within the range of estimates seen for other disease states and appeared to
      be larger in those reporting more severe disease.

PMID- 24886428
TI  - A PKC-SHP1 signaling axis desensitizes Fcgamma receptor signaling by reducing the
      tyrosine phosphorylation of CBL and regulates FcgammaR mediated phagocytosis.
AB  - BACKGROUND: Fcgamma receptors mediate important biological signals in myeloid
      cells including the ingestion of microorganisms through a process of
      phagocytosis. It is well-known that Fcgamma receptor (FcgammaR) crosslinking
      induces the tyrosine phosphorylation of CBL which is associated with FcgammaR
      mediated phagocytosis, however how signaling molecules coordinate to desensitize
      these receptors is unclear. An investigation of the mechanisms involved in
      receptor desensitization will provide new insight into potential mechanisms by
      which signaling molecules may downregulate tyrosine phosphorylation dependent
      signaling events to terminate important signaling processes. RESULTS: Using the
      U937IF cell line, we observed that FcgammaR1 crosslinking induces the tyrosine
      phosphorylation of CBL, which is maximal at 5 min. followed by a kinetic pattern
      of dephosphorylation. An investigation of the mechanisms involved in receptor
      desensitization revealed that pretreatment of U937IF or J774 cells with PMA
      followed by Fcgamma receptor crosslinking results in the reduced tyrosine
      phosphorylation of CBL and the abrogation of downstream signals, such as CBL-CRKL
      binding, Rac-GTP activation and the phagocytic response. Pretreatment of J774
      cells with GF109203X, a PKC inhibitor was observed to block dephosphorylation of
      CBL and rescued the phagocytic response. We demonstrate that the PKC induced
      desensitization of FcgammaR/ phagocytosis is associated with the inactivation of
      Rac-GTP, which is deactivated in a hematopoietic specific phosphatase SHP1
      dependent manner following ITAM stimulation. The effect of PKC on FcgammaR
      signaling is augmented by the transfection of catalytically active SHP1 and not
      by the transfection of catalytic dead SHP1 (C124S). CONCLUSIONS: Our results
      suggest a functional model by which PKC interacts with SHP1 to affect the
      phosphorylation state of CBL, the activation state of Rac and the negative
      regulation of ITAM signaling i.e. Fcgamma receptor mediated phagocytosis. These
      findings suggest a mechanism for Fcgamma receptor desensitization by which a
      serine-threonine kinase e.g. PKC downregulates tyrosine phosphorylation dependent
      signaling events via the reduced tyrosine phosphorylation of the complex adapter
      protein, CBL.

PMID- 24886431
TI  - Technical procedures for template-guided surgery for mandibular reconstruction
      based on digital design and manufacturing.
AB  - BACKGROUND: The occurrence of mandibular defects caused by tumors has been
      continuously increasing in China in recent years. Conversely, results of the
      repair of mandibular defects affect the recovery of oral function and patient
      appearance, and the requirements for accuracy and high surgical quality must be
      more stringent. Digital techniques--including model reconstruction based on
      medical images, computer-aided design, and additive manufacturing--have been
      widely used in modern medicine to improve the accuracy and quality of diagnosis
      and surgery. However, some special software platforms and services from
      international companies are not always available for most of researchers and
      surgeons because they are expensive and time-consuming. METHODS: Here, a new
      technical solution for guided surgery for the repair of mandibular defects is
      proposed, based on general popular tools in medical image processing, 3D (3
      dimension) model reconstruction, digital design, and fabrication via 3D printing.
      First, CT (computerized tomography) images are processed to reconstruct the 3D
      model of the mandible and fibular bone. The defect area is then replaced by
      healthy contralateral bone to create the repair model. With the repair model as
      reference, the graft shape and cutline are designed on fibular bone, as is the
      guide for cutting and shaping. The physical model, fabricated via 3D printing,
      including surgical guide, the original model, and the repair model, can be used
      to preform a titanium locking plate, as well as to design and verify the surgical
      plan and guide. In clinics, surgeons can operate with the help of the surgical
      guide and preformed plate to realize the predesigned surgical plan. RESULTS: With
      sufficient communication between engineers and surgeons, an optimal surgical plan
      can be designed via some common software platforms but needs to be translated to
      the clinic. Based on customized models and tools, including three surgical
      guides, preformed titanium plate for fixation, and physical models of the
      mandible, grafts for defect repair can be cut from fibular bone, shaped with high
      accuracy during surgery, and fixed with a well-fitting preformed locking plate,
      so that the predesigned plan can be performed in the clinic and the oral function
      and appearance of the patient are recovered. This method requires 20% less
      operating time compared with conventional surgery, and the advantages in cost and
      convenience are significant compared with those of existing commercial services
      in China. CONCLUSIONS: This comparison between two groups of cases illustrates
      that, with the proposed method, the accuracy of mandibular defect repair surgery
      is increased significantly and is less time-consuming, and patients are satisfied
      with both the recovery of oral function and their appearance. Until now, more
      than 15 cases have been treated with the proposed methods, so their feasibility
      and validity have been verified.

PMID- 24886432
TI  - Modifiable cardiovascular disease risk factors as predictors of dementia death:
      pooling of ten general population-based cohort studies.
AB  - BACKGROUND: With drug treatment for dementia being of limited effectiveness, the
      role of primary prevention, in particular the predictive value of modifiable
      cardiovascular disease risk factors, may warrant exploration. The evidence base
      is, however, characterised by discordant findings and is modest in size.
      Accordingly, we examined the association of modifiable cardiovascular disease
      risk factors with dementia death. DESIGN AND METHODS: We pooled raw data from 10
      UK general population-based prospective cohort studies within the context of an
      individual participant meta-analysis. RESULTS: A total of 103,764 men and women
      were followed up for a mean of 8 years giving rise to 443 dementia-related deaths
      and 2612 cardiovascular disease deaths. Cardiovascular disease mortality was, as
      anticipated, associated with the full range of risk factors under study,
      including raised blood pressure, smoking, diabetes, physical inactivity. By
      contrast, dementia death was related to very few of the cardiovascular disease
      risk factors: of those classified as modifiable, only smoking was associated with
      a raised risk and higher levels of non-HDL with a lower risk. CONCLUSIONS: In the
      present individual participant meta-analysis, there was limited evidence that
      cardiovascular disease risk factors were related to dementia death.

PMID- 24886433
TI  - Exploring mechanisms of diet-colon cancer associations through candidate
      molecular interaction networks.
AB  - BACKGROUND: Epidemiological studies in the recent years have investigated the
      relationship between dietary habits and disease risk demonstrating that diet has
      a direct effect on public health. Especially plant-based diets -fruits,
      vegetables and herbs- are known as a source of molecules with pharmacological
      properties for treatment of several malignancies. Unquestionably, for developing
      specific intervention strategies to reduce cancer risk there is a need for a more
      extensive and holistic examination of the dietary components for exploring the
      mechanisms of action and understanding the nutrient-nutrient interactions. Here,
      we used colon cancer as a proof-of-concept for understanding key regulatory sites
      of diet on the disease pathway. RESULTS: We started from a unique vantage point
      by having a database of 158 plants positively associated to colon cancer
      reduction and their molecular composition (~3,500 unique compounds). We generated
      a comprehensive picture of the interaction profile of these edible and non-edible
      plants with a predefined candidate colon cancer target space consisting of ~1,900
      proteins. This knowledge allowed us to study systematically the key components in
      colon cancer that are targeted synergistically by phytochemicals and identify
      statistically significant and highly correlated protein networks that could be
      perturbed by dietary habits. CONCLUSION: We propose here a framework for
      interrogating the critical targets in colon cancer processes and identifying
      plant-based dietary interventions as important modifiers using a systems chemical
      biology approach. Our methodology for better delineating prevention of colon
      cancer by nutritional interventions relies heavily on the availability of
      information about the small molecule constituents of our diet and it can be
      expanded to any other disease class that previous evidence has linked to
      lifestyle.

PMID- 24886434
TI  - Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of
      cancer stem cell-like characteristics and a reduced tumor burden.
AB  - BACKGROUND: Current treatment of ovarian cancer patients with chemotherapy leaves
      behind a residual tumor which results in recurrent ovarian cancer within a short
      time frame. We have previously demonstrated that a single short-term treatment of
      ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell
      (CSC)-like enriched residual population which generated significantly greater
      tumor burden compared to the tumor burden generated by control untreated cells.
      In this report we looked at the mechanisms of the enrichment of CSC-like residual
      cells in response to paclitaxel treatment. METHODS: The mechanism of survival of
      paclitaxel-treated residual cells at a growth inhibitory concentration of 50%
      (GI50) was determined on isolated tumor cells from the ascites of recurrent
      ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and
      in a mouse xenograft model. RESULTS: Treatment of isolated tumor cells from the
      ascites of ovarian cancer patients and HEY ovarian cancer cell line with
      paclitaxel resulted in a CSC-like residual population which coincided with the
      activation of Janus activated kinase 2 (JAK2) and signal transducer and
      activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both
      paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were
      inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 MUM) in
      vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY
      cells in mice resulted in a significantly reduced tumor burden compared to that
      seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor
      xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and
      CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts,
      compared to paclitaxel only-treated cell-derived xenografts. These results were
      consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel
      and CYT387-treated cell-derived xenografts compared to paclitaxel only-treated
      cell derived xenografts. CONCLUSIONS: This proof of principle study demonstrates
      that inhibition of the JAK2/STAT3 pathway by the addition of CYT387 suppresses
      the 'stemness' profile in chemotherapy-treated residual cells in vitro, which is
      replicated in vivo, leading to a reduced tumor burden. These findings have
      important implications for ovarian cancer patients who are treated with taxane
      and/or platinum-based therapies.

PMID- 24886436
TI  - MP-Align: alignment of metabolic pathways.
AB  - BACKGROUND: Comparing the metabolic pathways of different species is useful for
      understanding metabolic functions and can help in studying diseases and
      engineering drugs. Several comparison techniques for metabolic pathways have been
      introduced in the literature as a first attempt in this direction. The approaches
      are based on some simplified representation of metabolic pathways and on a
      related definition of a similarity score (or distance measure) between two
      pathways. More recent comparative research focuses on alignment techniques that
      can identify similar parts between pathways. RESULTS: We propose a methodology
      for the pairwise comparison and alignment of metabolic pathways that aims at
      providing the largest conserved substructure of the pathways under consideration.
      The proposed methodology has been implemented in a tool called MP-Align, which
      has been used to perform several validation tests. The results showed that our
      similarity score makes it possible to discriminate between different domains and
      to reconstruct a meaningful phylogeny from metabolic data. The results further
      demonstrate that our alignment algorithm correctly identifies subpathways sharing
      a common biological function. CONCLUSION: The results of the validation tests
      performed with MP-Align are encouraging. A comparison with another proposal in
      the literature showed that our alignment algorithm is particularly well-suited to
      finding the largest conserved subpathway of the pathways under examination.

PMID- 24886435
TI  - Transcriptome assemblies for studying sex-biased gene expression in the guppy,
      Poecilia reticulata.
AB  - BACKGROUND: Sexually dimorphic phenotypes are generally associated with
      differential gene expression between the sexes. The study of molecular evolution
      and genomic location of these differentially expressed, or sex-biased, genes is
      important for understanding inter-sexual divergence under sex-specific selection
      pressures. Teleost fish provide a unique opportunity to examine this divergence
      in the presence of variable sex-determination mechanisms of recent origin. The
      guppy, Poecilia reticulata, displays sexual dimorphism in size, ornaments, and
      behavior, traits shaped by natural and sexual selection in the wild. RESULTS: To
      gain insight into molecular mechanisms underlying the guppy's sexual dimorphism,
      we assembled a reference transcriptome combining genome-independent as well as
      genome-guided assemblies and analyzed sex-biased gene expression between
      different tissues of adult male and female guppies. We found tissue-associated
      sex-biased expression of genes related to pigmentation, signal transduction, and
      spermatogenesis in males; and growth, cell-division, extra-cellular matrix
      organization, nutrient transport, and folliculogenesis in females. While most sex
      biased genes were randomly distributed across linkage groups, we observed
      accumulation of ovary-biased genes on the sex linkage group, LG12. Both testis
      biased and ovary-biased genes showed a significantly higher rate of non
      synonymous to synonymous substitutions (dN/dS) compared to unbiased genes.
      However, in somatic tissues only female-biased genes, including those co
      expressed in multiple tissues, showed elevated ratios of non-synonymous
      substitutions. CONCLUSIONS: Our work identifies a set of annotated gene products
      that are candidate factors affecting sexual dimorphism in guppies. The
      differential genomic distribution of gonad-biased genes provides evidence for sex
      specific selection pressures acting on the nascent sex chromosomes of the guppy.
      The elevated rates of evolution of testis-biased and female-biased genes indicate
      differing evolution under distinct selection pressures on the reproductive versus
      non-reproductive tissues.

PMID- 24886437
TI  - Identification of mesenchymal stem cells and osteogenic factors in bone marrow
      aspirate and peripheral blood for spinal fusion by flow cytometry and proteomic
      analysis.
AB  - BACKGROUND: An in vivo animal study and a prospective clinical study have
      indicated that bone marrow aspirate (BMA) augments spinal arthrodesis. However,
      there is no quantified data to explain why fusion rate can be augmented by BMA in
      lumbar posterolateral fusion. METHODS: To analyze the proportion of mesenchymal
      stem cells (MSCs) and osteogenic factors in human BMA and peripheral blood (PB)
      of the same patient. Autologous BMA and PB from the patients were analyzed by
      flow cytometry (FACS) using cell markers for MSCs. The osteogenic potential of
      MSCs was determined by alkaline phosphatase (ALP) activity and calcium level
      quantification. Proteomics were used for the qualitative and quantitative mapping
      of the whole proteome from BMA and PB plasma. The mass-to-charge ratio was
      calculated by time-of-flight mass spectrometry (TOF-MS). The overexpression of
      protein was confirmed using Western blot analysis. RESULTS: The proportion of
      MSCs (CD34-/CD29+/CD105+) was higher in the BMA than that in the PB. Colony
      forming cell (CFC) assays suggested that fewer colonies were formed in PB
      cultures than in BMA culture. There was no significant difference in the
      osteogenic potential of the MSCs between the PB and BMA. Proteomic mass
      spectrometry assays suggested that the levels of catalase (osteoclast inhibitor)
      and glutathione peroxidase 3 (osteogenic biomarker) were higher in the BMA than
      those in the PB, and this was confirmed by Western blot analysis. CONCLUSIONS:
      The proportions of MSCs and osteogenic factors were higher in the BMA than in the
      PB. This may explain why fusion rate can be augmented by BMA in lumbar
      posterolateral fusion.

PMID- 24886438
TI  - A comparison of maternal and neonatal outcomes between water immersion during
      labor and conventional labor and delivery.
AB  - BACKGROUND: Water immersion during the first stage of labor can reduce the length
      of the first stage and epidural/spinal analgesia use; however, there is limited
      information regarding other outcomes. Our purpose was to compare maternal and
      neonatal outcomes of women who underwent water immersion during the first stage
      of labor with those who underwent conventional labor and delivery. METHODS:
      Healthy primipara with singleton pregnancies and cephalic presentation were
      included in the study. Patients were allowed to choose water immersion during
      labor or conventional labor and delivery. For water immersion, the water
      temperature was maintained at 35-38 degrees C and subjects left the tub on
      complete cervical dilatation. A visual analogue scale (VAS) was used to assess
      pain during labor. Other outcome measures included duration of labor, type of
      delivery, blood loss, pelvic floor dysfunction and symptoms of stress urinary
      incontinence (SUI) at 42 days after delivery, infant Apgar scores, and need for
      transfer of the infant to the neonatal intensive care unit. RESULTS: Thirty eight
      subjects (mean age, 28.66 +/- 3.08 y) received water immersion and 70 (mean age,
      27.89 +/- 2.99 y) underwent conventional labor and delivery. There were no
      differences in maternal height, weight, age, gestational age, gravidity, and
      newborn weight between the groups (all, p>0.05). VAS pain scores were
      significantly greater in the conventional labor group at 30 min and 60 min after
      a cervical dilatation of 3 cm (30 min: 10 [9, 10] vs. 6 [5, 8]; 60 min: 10 [10,
      10] vs. 7 [6, 8], respectively, both, p<0.001). The duration of labor and
      postpartum bleeding were similar between the groups (all, p>0.05). The cesarean
      section rate was higher in the conventional labor group (32.9% vs. 13.2%,
      p=0.026). The 1-minute and 5-minute Apgar scores were similar between the groups.
      Maternal and neonatal culture results were similar between the groups. SUI
      symptoms at 42 days after delivery was significantly higher in the conventional
      labor group (25.5% vs. 6.1%, respectively, p=0.035). CONCLUSIONS: Water immersion
      can reduce labor pain, and is associated with a lower rate of cesarean delivery
      and SUI symptoms at 42 days.

PMID- 24886439
TI  - Bone marrow metastasis in primary bronchial mucoepidermoid carcinoma: a case
      report.
AB  - Primary bronchial mucoepidermoid carcinoma in the lung is relatively rare. It
      rarely presents with the highly malignant biological characteristic of bone
      marrow metastasis. We describe a case of this disease with bone marrow
      metastasis. A 56-year-old man with the primary manifestation of bone pain and
      bloodstained sputum had two abnormal shadows on the left inferior lobar bronchus
      and peripheral tissue of the lower lobe of the left lung, respectively. Computed
      tomography-guided percutaneous puncture biopsy and bone imaging confirmed the
      diagnosis of high-grade bronchial mucoepidermoid carcinoma with bone metastasis.
      However, the patient soon presented with progressive hemoglobin and platelet
      decline and severe multi-organ hemorrhage. Subsequently, we performed bone marrow
      aspiration and biopsy, which revealed malignant cells and necrosis. The patient
      deteriorated rapidly from the disease, and died on the 16th day of admission. We
      hope that this case report will increase awareness of the possibility of primary
      high-grade bronchial mucoepidermoid carcinoma metastasizing to the bone marrow,
      which might be a poor prognostic factor. 

PMID- 24886440
TI  - Strategies to reduce safety violations for working from heights in construction
      companies: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Safety measures should be applied to reduce work-related fatal and
      non-fatal fall injuries. However, according to the labor inspectorate, more than
      80% of Dutch construction sites violate safety regulations for working from
      heights. To increase compliance with safety regulations, employers and workers
      have to select, implement and monitor safety measures. To facilitate this
      behavioral change, stimulating knowledge awareness and personalized feedback are
      frequently advocated behavior change techniques. For this study, two behavior
      change strategies have been developed in addition to the announcement of safety
      inspections by the labor inspectorate. These strategies consist of 1) face-to
      face contacts with safety consultants and 2) direct mail with access to internet
      facilities. The objective of this study is to evaluate the effectiveness of these
      two strategies on the safety violations for working from heights, the process and
      the cost measures. METHODS/DESIGN: This study is a block randomized intervention
      trial in 27 cities to establish the effects of the face-to-face guidance strategy
      (N = 9), a direct mailing strategy (N = 9) and a control condition of no guidance
      (N = 9) on safety violations to record by labor inspectors after three months. A
      process evaluation for both strategies will be performed to determine program
      implementation (reach, dose delivered and dose received), satisfaction, knowledge
      and perceived safety behavior. A cost analysis will be performed to establish the
      financial costs for both strategies. The present study is in accordance with the
      CONSORT statement. DISCUSSION: This study increases insight into performing
      practice-based randomized controlled trials. The outcome will help to evaluate
      the effect of two guidance strategies on safety violations. If these strategies
      are effective, implementation of these strategies through the national institute
      of safety and health or labor inspectorate can take place to guide construction
      companies in complying with safety regulations. TRIAL REGISTRATION: NTR 4298 on
      29-nov-2013.

PMID- 24886441
TI  - Magnetic resonance myocardial perfusion imaging in the diagnosis of functionally
      significant obstructive coronary artery disease: a systematic review protocol.
AB  - BACKGROUND: Cardiac magnetic resonance (CMR) myocardial perfusion imaging has
      been suggested as a non-invasive alternative to pressure wire guided fractional
      flow reserve (FFR) in detecting haemodynamically significant obstructive coronary
      artery disease (CAD). The objective of this systematic review is to determine the
      diagnostic accuracy of CMR and to compare it to FFR. METHODS/DESIGN: A systematic
      review of diagnostic test accuracy of CMR and FFR will be conducted. Relevant
      English-language articles published before November 2013 in Medline, PubMed,
      EMBASE, Google scholar, Scopus and Cochrane databases will be identified.
      Relevant referenced articles from those selected will also be analysed. Articles
      describing diagnostic studies that compared CMR to FFR in patients with known or
      suspected coronary artery disease will be included. Two investigators will
      independently screen, assess quality and extract data from the selected articles.
      The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool will be
      used to assess methodological quality. STATA 13 (the xtmelogit command) software
      will be used to calculate bivariate random effects models and estimate pooled
      sensitivity and specificity with 95% confidence intervals. Forests plots and
      summary receiver operating characteristics curves will also be generated. Sub
      group pooled analyses using image quality of CMR (in terms of magnetic flux
      density - Tesla) and basis of analyses (coronary arterial territory vs. patients
      basis) at different FFR cutoffs (<=0.75 and <=0.8) will also be performed.
      DISCUSSION: This systematic review will help to determine if CMR is an adequate
      alternative to FFR in the diagnosis of significant and obstructive CAD. We will
      also be able to assess diagnostic accuracy of specific types of CMR scan at
      different FFR cutoffs. SYSTEMATIC REVIEW REGISTRATION: This systematic review had
      been registered at PROSPERO and the registration number is CRD42013006180.

PMID- 24886442
TI  - Role of non-coding RNAs in maintaining primary airway smooth muscle cells.
AB  - BACKGROUND: The airway smooth muscle (ASM) cell maintains its own proliferative
      rate and contributes to the inflammatory response in the airways, effects that
      are inhibited by corticosteroids, used in the treatment of airways diseases.
      OBJECTIVE: We determined the differential expression of mRNAs, microRNAs (miRNAs)
      and long noncoding RNA species (lncRNAs) in primary ASM cells following treatment
      with a corticosteroid, dexamethasone, and fetal calf serum (FCS). METHODS: mRNA,
      miRNA and lncRNA expression was measured by microarray and quantitative real-time
      PCR. RESULTS: A small number of miRNAs (including miR-150, -371-5p, -718, -940, 
      1181, -1207-5p, -1915, and -3663-3p) were decreased following exposure to
      dexamethasone and FCS. The mRNA targets of these miRNAs were increased in
      expression. The changes in mRNA expression were associated with regulation of ASM
      actin cytoskeleton. We also observed changes in expression of lncRNAs, including
      natural antisense, pseudogenes, intronic lncRNAs, and intergenic lncRNAs
      following dexamethasone and FCS. We confirmed the change in expression of three
      of these, LINC00882, LINC00883, PVT1, and its transcriptional activator, c-MYC.
      We propose that four of these lincRNAs (RP11-46A10.4, LINC00883, BCYRN1, and
      LINC00882) act as miRNA 'sponges' for 4 miRNAs (miR-150, -371-5p, -940, -1207
      5p). CONCLUSION: This in-vitro model of primary ASM cell phenotype was associated
      with the regulation of several ncRNAs. Their identification allows for in-vitro
      functional experimentation to establish causality with the primary ASM phenotype,
      and in airway diseases such as asthma and chronic obstructive pulmonary disease
      (COPD).

PMID- 24886443
TI  - PLA1A2 platelet polymorphism predicts mortality in prediabetic subjects of the
      population based KORA S4-Cohort.
AB  - OBJECTIVE: The genetic polymorphism concerning the beta3-subunit of platelet
      integrin receptor glycoprotein IIIa is held responsible for enhanced binding of
      adhesive proteins resulting in increased thrombogenic potential. Whether it is
      associated with mortality, HbA1c or platelet volume is tested prospectively in an
      epidemiological cohort. RESEARCH DESIGN AND METHODS: Population-based Cooperative
      Health Research in the Region of Augsburg (KORA) S4-Survey (N = 4,028) was
      investigated for prognostic value of PLA1A2-polymorphism regarding all-cause
      mortality, correlation with HbA1c, and mean platelet volume. Multivariate
      analysis was performed to investigate association between genotype and key
      variables. RESULTS: Prevalence of thrombogenic allele variant PLA2 was 15.0%.
      Multivariate analysis revealed no association between PLA1A2 polymorphism and
      mortality in the KORA-cohort. HbA1c was a prognostic marker of mortality in non
      diabetic persons resulting in J-shaped risk curve with dip at HbA1c = 5.5% (37
      mmol/mol), confirming previous findings regarding aged KORA-S4 participants (55
      75 years). PLA1A2 was significantly associated with elevated HbA1c levels in
      diabetic patients (N = 209) and reduced mean platelet volume in general
      population. In non-diabetic participants (N = 3,819), carriers of PLA2 allele
      variant presenting with HbA1c > 5.5% (37 mmol/mol) showed higher relative risk of
      mortality with increasing HbA1c. CONCLUSION: PLA1A2 polymorphism is associated
      with mortality in participants with HbA1c ranging from 5.5% (37 mmol/mol) to 6.5%
      (48 mmol/mol). Maintenance of euglycemic control and antiplatelet therapy are
      therefore regarded as effective primary prevention in this group.

PMID- 24886446
TI  - Prognosis: the "missing link" within the CanMEDS competency framework.
AB  - BACKGROUND: The concept of prognosis dates back to antiquity. Quantum advances in
      diagnostics and therapeutics have relegated this once highly valued core
      competency to an almost negligible role in modern medical practice. Medical
      curricula are devoid of teaching opportunities focused on prognosis. This void is
      driven by a corresponding relative dearth within physician competency frameworks.
      This study aims to assess the level of content related to prognosis within
      CanMEDS (Canadian Medical Education Directives for Specialists), a leading and
      prototypical physician competency framework. METHODS: A quantitative content
      analysis of CanMEDS competency framework was carried out to measure the extent of
      this deficiency. Foxit Reader 5.1 (Foxit Corporation), a keyword scanning
      software, was used to assess the CanMEDS 2005 framework documents of 29 physician
      specialties and 37 subspecialties across the seven physician roles (medical
      expert, communicator, collaborator, manager, health advocate, scholar, and
      professional). The keywords used in the search included prognosis, prognostic,
      prognosticate, and prognostication. RESULTS: Of the 29 specialties six (20.7%)
      contained at least one citation of the keyword "prognosis", and one (3.4%)
      contained one citation of the keyword "prognostic". Of the 37 subspecialties,
      sixteen (43.2%) contained at least one citation of the keyword "prognosis", and
      three (8.1%) contained at least one citation of the keyword "prognostic". The
      terms "prognosticate" and "prognostication" were completely absent from all
      CanMEDS 2005 documents. Overall, the combined citations for "prognosis" and
      "prognostic" were linked with the following competency roles: Medical Expert
      (80.3%), Scholar (11.5%), and Communicator (8.2%). CONCLUSIONS: Given the
      fundamental and foundational importance of prognosis within medical practice, it
      is recommended that physicians develop appropriate attitudes, skills and
      knowledge related to the formulation and communication of prognosis. The
      deficiencies within CanMEDS, demonstrated by this study, should be addressed in
      advance of the launch of its updated version in 2015.

PMID- 24886444
TI  - Glass ionomer ART sealant and fluoride-releasing resin sealant in fissure caries
      prevention--results from a randomized clinical trial.
AB  - BACKGROUND: The relative performance of ART sealant and fluoride-releasing resin
      sealant in preventing fissure caries in permanent molars was compared in a
      randomized clinical trial conducted in southern China (ClinicalTrials.gov
      NCT01829334). METHODS: After obtaining ethical approval, healthy schoolchildren
      who had permanent first molars with occlusal fissures which were sound but deep
      or presented with only incipient caries were recruited for the study. Included
      molars were randomly allocated into one of four parallel study groups in units of
      left/right teeth per mouth. Two of the four groups adopted the methods of ART or
      fluoride-releasing resin sealant placement while the other two groups adopted the
      topical fluoride application methods. Fissure status of the molars in each group
      was evaluated every 6 months. Development of dentine caries and sealant retention
      over 24 months in the molars in the two sealant-using groups was compared in this
      report. Outcome on cost-effectiveness of all four groups over 36 months will be
      reported elsewhere. RESULTS: At baseline, a total of 280 children (383 molars)
      with mean age 7.8 years were involved for the two sealant groups. After 24
      months, 261 children (357 molars) were followed. Proportions of molars with
      dentine caries were 7.3% and 3.9% in the ART sealant and fluoride-releasing resin
      sealant groups, respectively (chi-square test, p = 0.171). Life-table survival
      analysis showed that sealant retention (full and partial) rate over 24 months for
      the resin sealant (73%) was significantly higher than that (50%) for the ART
      sealant (p < 0.001). Molar survival (no development of dentine caries) rates in
      the ART sealant (93%) and fluoride-releasing resin sealant (96%) groups were not
      significantly different (p = 0.169). Multilevel logistic regression (GEE
      modeling) accounting for the effects of data clustering and confounding factors
      confirmed this finding. CONCLUSIONS: Though the retention of fluoride-releasing
      resin sealant was better than that of the ART sealant, their effectiveness in
      preventing fissure caries in permanent molars did not differ significantly over
      24 months. ART sealants could be a good alternative when and where resources for
      resin sealant placement are not readily available.

PMID- 24886445
TI  - Risk factors for post-ERCP pancreatitis: a systematic review of clinical trials
      with a large sample size in the past 10 years.
AB  - BACKGROUND: Post- endoscopic retrograde cholangiopancreatography (ERCP)
      pancreatitis (PEP) is the most common and most severe complication associated
      with diagnostic and therapeutic ERCP. A multivariate analysis of risk factors for
      PEP is essential for identifying patients at high risk and subsequently choosing
      other suitable diagnoses. METHODS: Pertinent publications were identified through
      systematic searches of MEDLINE, Elsevier, and Springer; we performed a systematic
      review of 12 clinical studies published in the past ten years, selected out of
      451 reviewed articles, in which risk factors for pancreatitis were identified.
      Seven probable risk factors were evaluated, and outcomes expressed in the case of
      dichotomous variables, as an odds ratio (OR) (with a 95% confidence interval, 95%
      CI). RESULTS: When the risk factors were analyzed, the OR for female gender was
      1.40 (95% CI 1.24 to 1.58); the OR for previous PEP was 3.23 (95% CI 2.48 to
      4.22); the OR for previous pancreatitis was 2.00 (95% CI 1.72 to 2.33); the OR
      for endoscopic sphincterotomy was 1.42 (95% CI 1.14 to 1.78); the OR for precut
      sphincterotomy was 2.11 (95% CI 1.72 to 2.59); the OR for Sphincter of Oddi
      dysfunction was 4.37 (95% CI 3.75 to 5.09); and the OR for non-prophylactic
      pancreatic duct stent was 2.10 (95% CI 1.63 to 2.69). CONCLUSIONS: It appears
      that female gender, previous PEP, previous pancreatitis, endoscopic
      sphincterotomy, precut sphincterotomy, Sphincter of Oddi dysfunction, and non
      prophylactic pancreatic duct stent are the risk factors for post-ERCP
      pancreatitis.

PMID- 24886447
TI  - Sexual experience and HIV-related knowledge among Belgian university students: a
      questionnaire study.
AB  - BACKGROUND: Adolescents are a risk group for acquiring sexually transmitted
      diseases, including HIV. Correct knowledge about transmission mechanisms is a
      prerequisite to taking appropriate precautions to avoid infection. This study
      aimed at assessing the level of HIV-related knowledge among university students
      as a first step in developing targeted interventions. We used a self-developed
      HIV knowledge questionnaire, supplemented with socio-demographic and sexual
      behaviour questions. The questionnaire was composed of 59 items from different
      existing questionnaires. It included general statements and statements about
      prevention, transmission and treatment of HIV. RESULTS: There were 357 (79.7%)
      female and 93 (20.3%) male participants and their median age was 20 (IQR 19-21).
      On average 42/59 (71.2%) questions were answered correctly, 5/59 (8.5%) were
      answered incorrectly and 12/59 (20.3%) were unknown . The best and worse scores
      were seen on the prevention questions and the treatment questions, respectively.
      HIV-related knowledge is higher in older students and in students with a health
      related education. Students with sexual experience, with five or more partners
      and students who have been tested on STDs have a higher HIV-related knowledge.
      CONCLUSIONS: Knowledge on prevention and transmission of HIV is fairly good among
      university students and knowledge is higher among students with more sexual
      experience. They still have some misconceptions (e.g. HIV is spread by
      mosquitoes) and they are ignorant of a substantial number of statements (e.g.
      risk for infection through oral sex).

PMID- 24886448
TI  - Temporal trends and risk factors for parathyroidectomy in the Swedish dialysis
      and transplant population - a nationwide, population-based study 1991 - 2009.
AB  - BACKGROUND: Many patients on renal replacement therapy (RRT) require
      parathyroidectomy (PTX). Trends and current rates of PTX on a national level are
      not known. Furthermore, it is not completely clear which factors influence rates
      of PTX. Thus, our aim was to investigate the incidence, regional distribution and
      factors associated with PTX as well as possible temporal changes, in the Swedish
      RRT population. METHODS: From the Swedish Renal Registry we extracted data on 20
      015 patients on RRT between 1991 and 2009. In these, 679 incident PTX (3.4%) were
      identified by linkage with the National Inpatient Registry, and the Scandinavian
      Quality Registry for Thyroid Parathyroid and Adrenal Surgery. Poisson models were
      used to estimate rates per calendar year, adjusted for risk factors such as
      gender, age, time with renal transplant, and underlying cause of renal disease.
      RESULTS: The PTX rate was 8.8/1 000 person-years. There was a significant
      increase 2001-2004 after which the rate fell, as compared with year 2000. Female
      gender, non-diabetic cause of renal disease and age between 40-55 were all
      associated with an increased frequency of PTX. CONCLUSION: The rise in PTX rates
      after year 2000 might reflect increasing awareness of the potential benefits of
      PTX. The introduction of calcimimetics and paricalcitol might explain the
      decreased rate after 2005.

PMID- 24886449
TI  - Pain relief from combined wound and intraperitoneal local anesthesia for patients
      who undergo laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice
      for gallbladder lesions, but it is not a pain-free procedure. This study explored
      the pain relief provided by combined wound and intraperitoneal local anesthetic
      use for patients who are undergoing LC. METHODS: Two-hundred and twenty
      consecutive patients undergoing LC were categorized into 1 of the following 4
      groups: local wound anesthetic after LC either with an intraperitoneal local
      anesthetic (W + P) (group 1) or without an intraperitoneal local anesthetic (W +
      NP) (group 2), or no local wound anesthetic after LC either with intraperitoneal
      local anesthetic (NW + P) (group 3) or without an intraperitoneal local
      anesthetic (NW + NP) (group 4). A visual analog scale (VAS) was used to assess
      postoperative pain. The amount of analgesic used and the duration of hospital
      stay were also recorded. RESULTS: The VAS was significantly lower immediately
      after LC for the W + P group than for the NW + NP group (5 vs. 6; p = 0.012).
      Patients in the W + P group received a lower total amount of meperidine during
      their hospital stay. They also had the shortest hospital stay after LC, compared
      to the patients in the other groups. CONCLUSION: Combined wound and
      intraperitoneal local anesthetic use after LC significantly decreased the
      immediate postoperative pain and may explain the reduced use of meperidine and
      earlier discharge of patients so treated.

PMID- 24886451
TI  - New case of trichorinophalangeal syndrome-like phenotype with a de novo
      t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene.
AB  - BACKGROUND: Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant
      genetic disorder characterised by distinctive craniofacial and skeletal
      abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at
      8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions
      affecting the same chromosome region and a familial translocation t(8;13) co
      segregating with TRPS, which do not encompass or disrupt the TRPS1 gene, have
      been reported. A deregulated expression of TRPS1 has been hypothesised as cause
      of the TRPS phenotype of these patients. CASE PRESENTATION: We report the
      clinical and molecular characterisation of a 57-year-old Caucasian woman carrying
      the t(2;8)(p16.1;q23.3) de novo balanced translocation. The proband presented
      with peculiar clinical features (severe craniofacial dysmorphism, alopecia
      universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and
      normal growth parameters) that partially overlap with TRPS I. Mutational and
      array CGH analyses ruled out any genetic defect affecting TRPS1 or genomic
      alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint
      mapping excluded disruption of TRPS1, and revealed that the chromosome 8q23.3
      breakpoint was located within the IVS10 of the long intergenic non-coding RNA
      LINC00536, at approximately 300 kb from the TRPS1 5' end. Conversely, the 2p16.1
      breakpoint mapped within a LINE sequence, in a region that lacks transcriptional
      regulatory elements. As a result of the translocation, nucleotide base pair
      additions and deletions were detected at both breakpoint junction fragments, and
      an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at
      approximately 325 kb from the TRPS1 promoter. CONCLUSIONS: We suggest that the
      disruption of the genomic architecture of cis regulatory elements downstream the
      TRPS1 5' region, combined with the translocation of a novel enhancer element
      nearby TRPS1, might be the pathogenetic mechanism underpinning the proband's
      phenotype. The clinical and genetic characterisation of the present subject
      allowed us to make a genetic diagnosis in the context of a known syndrome,
      contributing to a better comprehension of the complex transcriptional regulation
      of TRPS1 and TRPS ethiopathogenesis.

PMID- 24886450
TI  - Cost-effectiveness of interventions for increasing the possession of functioning
      smoke alarms in households with pre-school children: a modelling study.
AB  - BACKGROUND: The UK has one of the highest rates for deaths from fire and flames
      in children aged 0-14 years compared to other high income countries. Evidence
      shows that smoke alarms can reduce the risk of fire-related injury but little
      exists on their cost-effectiveness. We aimed to compare the cost effectiveness of
      different interventions for the uptake of 'functioning' smoke alarms and
      consequently for the prevention of fire-related injuries in children in the UK.
      METHODS: We carried out a decision model-based probabilistic cost-effectiveness
      analysis. We used a hypothetical population of newborns and evaluated the impact
      of living in a household with or without a functioning smoke alarm during the
      first 5 years of their life on overall lifetime costs and quality of life from a
      public health perspective. We compared seven interventions, ranging from usual
      care to more complex interventions comprising of education, free/low cost
      equipment giveaway, equipment fitting and/or home safety inspection. RESULTS:
      Education and free/low cost equipment was the most cost-effective intervention
      with an estimated incremental cost-effectiveness ratio of L34,200 per QALY gained
      compared to usual care. This was reduced to approximately L4,500 per QALY gained
      when 1.8 children under the age of 5 were assumed per household. CONCLUSIONS:
      Assessing cost-effectiveness, as well as effectiveness, is important in a public
      sector system operating under a fixed budget restraint. As highlighted in this
      study, the more effective interventions (in this case the more complex
      interventions) may not necessarily be the ones considered the most cost
      effective.

PMID- 24886452
TI  - Similar matrix alterations in alveolar and small airway walls of COPD patients.
AB  - BACKGROUND: Remodelling in COPD has at least two dimensions: small airway wall
      thickening and destruction of alveolar walls. Recent studies indicate that there
      is some similarity between alveolar and small airway wall matrix remodelling. The
      aim of this study was to characterise and assess similarities in alveolar and
      small airway wall matrix remodelling, and TGF-beta signalling in COPD patients of
      different GOLD stages. METHODS: Lung tissue sections of 14 smoking controls, 16
      GOLD II and 19 GOLD IV patients were included and stained for elastin and
      collagens as well as hyaluronan, a glycosaminoglycan matrix component and pSMAD2.
      RESULTS: Elastin was significantly decreased in COPD patients not only in
      alveolar, but also in small airway walls. Interestingly, both collagen and
      hyaluronan were increased in alveolar as well as small airway walls. The matrix
      changes were highly comparable between GOLD stages, with collagen content in the
      alveolar wall increasing further in GOLD IV. A calculated remodelling index,
      defined as elastin divided over collagen and hyaluronan, was decreased
      significantly in GOLD II and further lowered in GOLD IV patients, suggesting that
      matrix component alterations are involved in progressive airflow limitation.
      Interestingly, there was a positive correlation present between the alveolar and
      small airway wall stainings of the matrix components, as well as for pSMAD2. No
      differences in pSMAD2 staining between controls and COPD patients were found.
      CONCLUSIONS: In conclusion, remodelling in the alveolar and small airway wall in
      COPD is markedly similar and already present in moderate COPD. Notably, alveolar
      collagen and a remodelling index relate to lung function.

PMID- 24886453
TI  - Additive effects of blood glucose lowering drugs, statins and renin-angiotensin
      system blockers on all-site cancer risk in patients with type 2 diabetes.
AB  - BACKGROUND: Hyperglycemia is associated with increased risk of all-site cancer
      that may be mediated through activation of the renin-angiotensin-system (RAS) and
      3-hydroxy-3-methyl-glutaryl-coenzyme-A-reductase (HMGCR) pathways. We examined
      the joint associations of optimal glycemic control (HbA1c <7%), RAS inhibitors
      and HMGCR inhibitors on cancer incidence in patients with type 2 diabetes.
      METHODS: Patients with type 2 diabetes, with or without a history of cancer or
      prior exposure to RAS or HMGCR inhibitors at baseline were observed between 1996
      and 2005. All patients underwent a comprehensive assessment at baseline and were
      followed until the censored date at 2005 or their death. RESULTS: After a median
      follow-up period of 4.91 years (interquartile range, 2.81 to 6.98), 271 out of
      6,103 patients developed all-site cancer. At baseline, patients with incident
      cancers were older, had longer disease duration of diabetes, higher alcohol and
      tobacco use, and higher systolic blood pressure and albuminuria, but lower
      triglyceride levels and estimated glomerular filtration rate (P <0.05). Patients
      who developed cancers during follow-up were less likely to have started using
      statins (22.5% versus 38.6%, P <0.001), fibrates (5.9% versus 10.2%, P = 0.02),
      metformin (63.8% versus 74.5%, P <0.001) or thiazolidinedione (0.7% versus 6.8%,
      P <0.001) than those who remained cancer-free. After adjusting for co-variables,
      new treatment with metformin (hazard ratio: 0.39; 95% confidence interval: 0.25,
      0.61; P <0.001), thiazolidinedione (0.18; 0.04, 0.72; P = 0.015), sulphonylurea
      (0.44; 0.27, 0.73; P = 0.014), insulin (0.58; 0.38, 0.89; P = 0.01), statins
      (0.47; 0.31, 0.70; P <0.001) and RAS inhibitors (0.55; 0.39, 0.78; P <0.001) were
      associated with reduced cancer risk. Patients with all three risk factors of
      HbA1c >=7%, non-use of RAS inhibitors and non-use of statins had four-fold
      adjusted higher risk of cancer than those without any risk factors (incidence per
      1,000-person-years for no risk factors: 3.40 (0.07, 6.72); one risk factor: 6.34
      (4.19, 8.50); two risk factors: 8.40 (6.60, 10.20); three risk factors: 13.08
      (9.82, 16.34); P <0.001). CONCLUSIONS: Hyperglycemia may promote cancer growth
      that can be attenuated by optimal glycemic control and inhibition of the RAS and
      HMGCR pathways.

PMID- 24886454
TI  - DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase.
AB  - BACKGROUND: DUSP3 phosphatase, also known as Vaccinia-H1 Related (VHR)
      phosphatase, encoded by DUSP3/Dusp3 gene, is a relatively small member of the
      dual-specificity protein phosphatases. In vitro studies showed that DUSP3 is a
      negative regulator of ERK and JNK pathways in several cell lines. On the other
      hand, DUSP3 is implicated in human cancer. It has been alternatively described as
      having tumor suppressive and oncogenic properties. Thus, the available data
      suggest that DUSP3 plays complex and contradictory roles in tumorigenesis that
      could be cell type-dependent. Since most of these studies were performed using
      recombinant proteins or in cell-transfection based assays, the physiological
      function of DUSP3 has remained elusive. RESULTS: Using immunohistochemistry on
      human cervical sections, we observed a strong expression of DUSP3 in endothelial
      cells (EC) suggesting a contribution for this phosphatase to EC functions. DUSP3
      downregulation, using RNA interference, in human EC reduced significantly in
      vitro tube formation on Matrigel and spheroid angiogenic sprouting. However, this
      defect was not associated with an altered phosphorylation of the documented in
      vitro DUSP3 substrates, ERK1/2, JNK1/2 and EGFR but was associated with an
      increased PKC phosphorylation. To investigate the physiological function of
      DUSP3, we generated Dusp3-deficient mice by homologous recombination. The
      obtained DUSP3-/- mice were healthy, fertile, with no spontaneous phenotype and
      no vascular defect. However, DUSP3 deficiency prevented neo-vascularization of
      transplanted b-FGF containing Matrigel and LLC xenograft tumors as evidenced by
      hemoglobin (Hb) and FITC-dextran quantifications. Furthermore, we found that
      DUSP3 is required for b-FGF-induced microvessel outgrowth in the aortic ring
      assay. CONCLUSIONS: All together, our data identify DUSP3 as a new important
      player in angiogenesis.

PMID- 24886456
TI  - Identification of optimum scopes of environmental factors for snails using
      spatial analysis techniques in Dongting Lake Region, China.
AB  - BACKGROUND: Owing to the harmfulness and seriousness of Schistosomiasis japonica
      in China, the control and prevention of S. japonica transmission are imperative.
      As the unique intermediate host of this disease, Oncomelania hupensis plays an
      important role in the transmission. It has been reported that the snail
      population in Qiangliang Lake district, Dongting Lake Region has been naturally
      declining and is slowly becoming extinct. Considering the changes of
      environmental factors that may cause this phenomenon, we try to explore the
      relationship between circumstance elements and snails, and then search for the
      possible optimum scopes of environmental factors for snails. METHODS: Moisture
      content of soil, pH, temperature of soil and elevation were collected by
      corresponding apparatus in the study sites. The LISA statistic and GWR model were
      used to analyze the association between factors and mean snail density, and the
      values in high-high clustered areas and low-low clustered areas were extracted to
      find out the possible optimum ranges of these elements for snails. RESULTS: A
      total of 8,589 snail specimens were collected from 397 sampling sites in the
      study field. Besides the mean snail density, three environmental factors
      including water content, pH and temperature had high spatial autocorrelation. The
      spatial clustering suggested that the possible optimum scopes of moisture
      content, pH, temperature of the soil and elevation were 58.70 to 68.93%, 6.80 to
      7.80, 22.73 to 24.23 degrees C and 23.50 to 25.97 m, respectively. Moreover, the
      GWR model showed that the possible optimum ranges of these four factors were
      36.58 to 61.08%, 6.541 to 6.89, 24.30 to 25.70 degrees C and 23.50 to 29.44 m,
      respectively. CONCLUSION: The results indicated the association between snails
      and environmental factors was not linear but U-shaped. Considering the results of
      two analysis methods, the possible optimum scopes of moisture content, pH,
      temperature of the soil and elevation were 58.70% to 68.93%, 6.6 to 7.0, 22.73
      degrees C to 24.23 degrees C, and 23.5 m to 26.0 m, respectively. The findings in
      this research will help in making an effective strategy to control snails and
      provide a method to analyze other factors.

PMID- 24886457
TI  - Potential risk of alpha-glucosidase inhibitor administration in prostate cancer
      external radiotherapy by exceptional rectal gas production: a case report.
AB  - INTRODUCTION: Radiotherapy is a standard treatment for prostate cancer, and image
      guided radiotherapy is increasingly being used to aid precision of dose delivery
      to targeted tissues. However, precision during radiotherapy cannot be maintained
      when unexpected intrafraction organ motion occurs. CASE PRESENTATION: We report
      our experience of internal organ motion caused by persistent gas production in a
      patient taking an alpha-glucosidase inhibitor. A 68-year-old Japanese man with
      prostate cancer visited our institution for treatment with helical tomotherapy.
      He suffered from diabetes mellitus and took an alpha-glucosidase inhibitor.
      Routine treatment planning computed tomography showed a large volume of rectal
      gas; an enema was given to void the rectum. Subsequent treatment planning
      computed tomography again showed a large volume of gas. After exercise (walking)
      to remove the intestinal gas, a third scan was performed as a test scan without
      tight fixation, which showed a sufficiently empty rectum for planning. However,
      after only a few minutes, treatment planning computed tomography again showed
      extreme accumulation of gas. Therefore, we postponed treatment planning computed
      tomography and consulted his doctor to suspend the alpha-glucosidase inhibitor,
      which was the expected cause of his persistent gas. Four days after the alpha
      glucosidase inhibitor regimen was suspended, we took a fourth treatment planning
      computed tomography and made a treatment plan without gas accumulation.
      Thereafter, the absence of rectal gas accumulation was confirmed using daily
      megavolt computed tomography before treatment, and the patient received 37
      fractions of intensity-modified radiotherapy at 74 Gy without rectal gas
      complications. In this case study, the alpha-glucosidase inhibitor induced the
      accumulation of intestinal gas, which may have caused unexpected organ motion,
      untoward reactions, and insufficient doses to clinical targets. CONCLUSIONS: We
      suggest that patients who are taking an alpha-glucosidase inhibitor for diabetes
      should discontinue use of that particular medicine prior to beginning
      radiotherapy.

PMID- 24886455
TI  - Effectiveness of mechanical traction as a non-surgical treatment for carpal
      tunnel syndrome compared to care as usual: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is a common condition (prevalence of 4%)
      where the median nerve is compressed within the carpal tunnel resulting in
      numbness, tingling, and pain in the hand. Current non-surgical treatment options
      (oral medication, corticosteroid injections, splinting, exercise, and
      mobilization) show limited effects, especially in the long-term. Carpal tunnel
      release (CTR) surgery is effective in 70 to 75% of patients, but is relatively
      invasive and can be accompanied by complications. In an observational study,
      mechanical traction proved to be effective in up to 70% of patients directly
      after treatment and in 60% after two years follow-up. This randomized controlled
      trial (RCT) will examine the effectiveness of mechanical traction compared to
      care as usual in CTS. METHODS/DESIGN: Patients diagnosed with CTS will be
      recruited from an outpatient neurology clinic and randomly assigned to the
      intervention group (mechanical traction) or the control group (care as usual).
      Participants in the intervention group will receive 12 treatments with mechanical
      traction during six consecutive weeks. Primary outcome is symptom severity and
      functional status, which are measured with the Boston Carpel Tunnel Questionnaire
      (BCTQ). Secondary outcomes are quality of life (WHOQOL-BREF), health related
      resource utilization, and absenteeism from work. Outcomes will be assessed at
      baseline, and at 3, 6, and 12 months after inclusion. Linear mixed effect models
      will be used to determine the change from baseline at 12 months on the BCTQ,
      WHOQOL-BREF, absenteeism from work and health related resource utilization. The
      baseline measurement, change from baseline at three and six months, as well as
      duration of symptoms until inclusion, age, gender, and co-morbidity will be
      included as covariates The Pearson's correlation coefficient will be generated to
      assess the correlation between depression and anxiety and treatment outcome.
      DISCUSSION: Since current non-surgical treatment options are not effective long
      term and CTR is relatively invasive, there is a need for an effective and non
      invasive treatment option. Mechanical traction is a safe treatment option that
      may provide a good alternative for the usual care. Considering the prevalence of
      CTS, the study is of great clinical value to a large patient population. TRIAL
      REGISTRATION: Clinical Trials NL44692.008.13 (registered on 19 September 2013).

PMID- 24886458
TI  - Efficacy of early immunomodulator therapy on the outcomes of Crohn's disease.
AB  - BACKGROUND: The natural course of Crohn's disease (CD), with continuing relapses
      and remissions, leads to irreversible intestinal damage. Early adoption of
      immunomodulator therapy has been proposed in order to address this; however, it
      is still uncertain whether early immunomodulator therapy could affect the natural
      course of the disease in real practice. We evaluated the efficacy of such therapy
      on the prognosis of newly diagnosed patients with CD. METHODS: This retrospective
      study included 168 patients who were newly diagnosed with CD and who started
      treatment at Severance Hospital, Seoul, Korea between January 2006 and March
      2013. The short- and long-term outcomes were compared between patients treated
      with early immunomodulator therapy and those treated with conventional therapy.
      RESULTS: A Kaplan-Meier analysis identified that administration of
      immunomodulators within 6 months after diagnosis of CD was superior to
      conventional therapy in terms of clinical remission and corticosteroid-free
      remission rates (P=0.043 and P=0.035). However, P=0.827). Patients with a
      baseline elevated CRP level were more likely to relapse (P<0.005). Drug-related
      adverse events were more frequent in the early immunomodulator therapy group than
      in the conventional therapy group P=0.029). CONCLUSIONS: Early immunomodulator
      therapy was more effective than conventional therapy in inducing remission, but
      not in preventing relapse. Baseline high CRP level was a significant indicator of
      relapse.

PMID- 24886459
TI  - Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and
      potential therapeutic prospects.
AB  - Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by
      progressive dissemination of mucinous tumors and mucinous ascites in the abdomen
      and pelvis. PMP is a rare disease with an estimated incidence of 1-2 out of a
      million. Clinically, PMP usually presents with a variety of unspecific signs and
      symptoms, including abdominal pain and distention, ascites or even bowel
      obstruction. It is also diagnosed incidentally at surgical or non-surgical
      investigations of the abdominopelvic viscera. PMP is a neoplastic disease
      originating from a primary mucinous tumor of the appendix with a distinctive
      pattern of the peritoneal spread. Computed tomography and histopathology are the
      most reliable diagnostic modalities. The differential diagnosis of the disease
      includes secondary peritoneal carcinomatoses and some rare peritoneal conditions.
      Optimal elimination of mucin and the mucin-secreting tumor comprises the current
      standard of care for PMP offered in specialized centers as visceral resections
      and peritonectomy combined with intraperitoneal chemotherapy. This
      multidisciplinary approach has reportedly provided a median survival rate of 16.3
      years, a median progression-free survival rate of 8.2 years and 10- and 15-year
      survival rates of 63% and 59%, respectively. Despite its indolent, bland nature
      as a neoplasm, PMP is a debilitating condition that severely impacts quality of
      life. It tends to be diagnosed at advanced stages and frequently recurs after
      treatment. Being ignored in research, however, PMP remains a challenging,
      enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid
      complications closely correspond with the multifocal distribution of the secreted
      mucin collections and mucin-secreting implants. Novel strategies are thus
      required to facilitate macroscopic, as well as microscopic, elimination of mucin
      and its source as the key components of the disease. In this regard, MUC2, MUC5AC
      and MUC5B have been found as the secreted mucins of relevance in PMP. Development
      of mucin-targeted therapies could be a promising avenue for future research which
      is addressed in this article.

PMID- 24886462
TI  - The well-being of community-dwelling near-centenarians and centenarians in Hong
      Kong: a qualitative study.
AB  - BACKGROUND: Hong Kong has one of the highest life expectancy rankings in the
      world. The number of centenarians and near-centenarians has been increasing
      locally and internationally. The relative growth of this population is a topic of
      immense importance for population and health policy makers. Living long and
      living well are two overlapping but distinct research topics. We previously
      conducted a quantitative study on 153 near-centenarians and centenarians to
      explore a wide range of biopsychosocial correlates of health and "living long".
      This paper reports a follow-up qualitative study examining the potential
      correlates of "living well" among near-centenarians and centenarians in Hong
      Kong. METHODS: Six cognitively, physically, and psychologically sound community
      dwelling elders were purposively recruited from a previous quantitative study.
      Semi-structured interviews were conducted. RESULTS: Four major themes related to
      living long and well emerged from the responses of the participants: (a) Positive
      relations with others, (b) Positive events and happiness, (c) Hope for the
      future, and (d) Positive life attitude. Specifically, we found that having good
      interpersonal relationships, possessing a collection of positive life events, and
      maintaining salutary attitudes towards life are considered as important to
      psychological well-being by long-lived adults in Hong Kong. Most participants
      perceived their working life as most important to their life history and retired
      at very old ages. CONCLUSIONS: These findings also shed light on the
      relationships between health, work, and old age.

PMID- 24886461
TI  - Inorganic polyphosphate regulates neuronal excitability through modulation of
      voltage-gated channels.
AB  - BACKGROUND: Inorganic polyphosphate (polyP) is a highly charged polyanion capable
      of interacting with a number of molecular targets. This signaling molecule is
      released into the extracellular matrix by central astrocytes and by peripheral
      platelets during inflammation. While the release of polyP is associated with both
      induction of blood coagulation and astrocyte extracellular signaling, the role of
      secreted polyP in regulation of neuronal activity remains undefined. Here we test
      the hypothesis that polyP is an important participant in neuronal signaling.
      Specifically, we investigate the ability of neurons to release polyP and to
      induce neuronal firing, and clarify the underlying molecular mechanisms of this
      process by studying the action of polyP on voltage gated channels. RESULTS: Using
      patch clamp techniques, and primary hippocampal and dorsal root ganglion cell
      cultures, we demonstrate that polyP directly influences neuronal activity,
      inducing action potential generation in both PNS and CNS neurons.
      Mechanistically, this is accomplished by shifting the voltage sensitivity of NaV
      channel activation toward the neuronal resting membrane potential, the block KV
      channels, and the activation of CaV channels. Next, using calcium imaging we
      found that polyP stimulates an increase in neuronal network activity and induces
      calcium influx in glial cells. Using in situ DAPI localization and live imaging,
      we demonstrate that polyP is naturally present in synaptic regions and is
      released from the neurons upon depolarization. Finally, using a biochemical assay
      we demonstrate that polyP is present in synaptosomes and can be released upon
      their membrane depolarization by the addition of potassium chloride. CONCLUSIONS:
      We conclude that polyP release leads to increased excitability of the neuronal
      membrane through the modulation of voltage gated ion channels. Together, our data
      establishes that polyP could function as excitatory neuromodulator in both the
      PNS and CNS.

PMID- 24886460
TI  - Screening and hit evaluation of a chemical library against blood-stage Plasmodium
      falciparum.
AB  - BACKGROUND: In view of the need to continuously feed the pipeline with new anti
      malarial agents adapted to differentiated and more stringent target product
      profiles (e.g., new modes of action, transmission-blocking activity or long
      duration chemo-protection), a chemical library consisting of more than 250,000
      compounds has been evaluated in a blood-stage Plasmodium falciparum growth
      inhibition assay and further assessed for chemical diversity and novelty.
      METHODS: The selection cascade used for the triaging of hits from the chemical
      library started with a robust three-step in vitro assay followed by an in silico
      analysis of the resulting confirmed hits. Upon reaching the predefined
      requirements for selectivity and potency, the set of hits was subjected to
      computational analysis to assess chemical properties and diversity. Furthermore,
      known marketed anti-malarial drugs were co-clustered acting as 'signposts' in the
      chemical space defined by the hits. Then, in cerebro evaluation of the chemical
      structures was performed to identify scaffolds that currently are or have been
      the focus of anti-malarial medicinal chemistry programmes. Next, prioritization
      according to relaxed physicochemical parameters took place, along with the search
      for structural analogues. Ultimately, synthesis of novel chemotypes with desired
      properties was performed and the resulting compounds were subsequently retested
      in a P. falciparum growth inhibition assay. RESULTS: This screening campaign led
      to a 1.25% primary hit rate, which decreased to 0.77% upon confirmatory repeat
      screening. With the predefined potency (EC50 < 1 MUM) and selectivity (SI > 10)
      criteria, 178 compounds progressed to the next steps where chemical diversity,
      physicochemical properties and novelty assessment were taken into account. This
      resulted in the selection of 15 distinct chemical series. CONCLUSION: A selection
      cascade was applied to prioritize hits resulting from the screening of a medium
      sized chemical library against blood-stage P. falciparum. Emphasis was placed on
      chemical novelty whereby computational clustering, data mining of known anti
      malarial chemotypes and the application of relaxed physicochemical filters, were
      key to the process. This led to the selection of 15 chemical series from which
      ten confirmed their activity when newly synthesized sample were tested.

PMID- 24886463
TI  - Saving time and money: a validation of the self ratings on the prospective NIMH
      Life-Chart Method (NIMH-LCM).
AB  - BACKGROUND: Careful observation of the longitudinal course of bipolar disorders
      is pivotal to finding optimal treatments and improving outcome. A useful tool is
      the daily prospective Life-Chart Method, developed by the National Institute of
      Mental Health. However, it remains unclear whether the patient version is as
      valid as the clinician version. METHODS: We compared the patient-rated version of
      the Lifechart (LC-self) with the Young-Mania-Rating Scale (YMRS), Inventory of
      Depressive Symptoms-Clinician version (IDS-C), and Clinical Global Impression
      Bipolar version (CGI-BP) in 108 bipolar I and II patients who participated in the
      Naturalistic Follow-up Study (NFS) of the German centres of the Bipolar
      Collaborative Network (BCN; formerly Stanley Foundation Bipolar Network). For
      statistical evaluation, levels of severity of mood states on the Lifechart were
      transformed numerically and comparison with affective scales was performed using
      chi-square and t tests. For testing correlations Pearson's coefficient was
      calculated. RESULTS: Ratings for depression of LC-self and total scores of IDS-C
      were found to be highly correlated (Pearson coefficient r = -.718; p < .001),
      whilst the correlation of ratings for mania with YMRS compared to LC-self were
      slightly less robust (Pearson coefficient r = .491; p = .001). These results were
      confirmed by good correlations between the CGI-BP IA (mania), IB (depression) and
      IC (overall mood state) and the LC-self ratings (Pearson coefficient r = .488, r
      = .721 and r = .65, respectively; all p < .001). CONCLUSIONS: The LC-self shows a
      significant correlation and good concordance with standard cross sectional
      affective rating scales, suggesting that the LC-self is a valid and time and
      money saving alternative to the clinician-rated version which should be
      incorporated in future clinical research in bipolar disorder. Generalizability of
      the results is limited by the selection of highly motivated patients in
      specialized bipolar centres and by the open design of the study.

PMID- 24886464
TI  - Gender differences in mortality and risk factors in a 13-year cohort study of
      street-recruited injecting drug users.
AB  - BACKGROUND: Injecting drug users (IDUs) are at risk of premature mortality. This
      study examined gender differences in mortality, risk factors, and causes of death
      among IDUs. METHODS: In a 13-year cohort study including 172 street-recruited
      IDUs from Oslo, Norway in 1997, interview data was merged with the National Cause
      of Death Registry. Crude mortality rate (CMR) and indirect standardized mortality
      ratio (SMR) were estimated with 95% confidence intervals (CI). A log-logistic
      multivariate survival analysis model was estimated for the full sample. For a
      smaller data set (1.1.1998-31.12.2004) the influence of substitution treatment
      and prison were assessed using cox regression survival analysis. RESULTS: Eight
      females and 37 males died. Acute intoxications were the most common cause of
      death. Women were more at risk in the short-term, but more protected in the long
      term. CMR was 16.0 [95% CI 8.0, 31.9] for women and 26.0 [95% CI 18.0, 35.8]) for
      men. SMR was 39.4 [95% CI 0.2, 220.8]) for women and 21.3 [95% CI 5.7, 54.1] for
      men. More women injected heroin (98% vs. 88% [x2 = 3.5, p = 0.063]), used
      prescription drugs (73% vs. 52% [x2 = 5.6, p = 0.018]) and combined these to
      inject (45% vs. 26% [x2 = 5.9, p = 0.015]). Mixing prescription drugs in heroin
      injections, and sex work (only women) were associated with decreased survival
      time. There were no gender differences in access to substitution treatment, while
      significantly more men had been in prison (74% vs. 51% [x2 = 7.5, p = 0.006]).
      The instance of substitution treatment and prison significantly decreased the
      mortality risk. Prison release increased the risk, but not statistically
      significantly. CONCLUSIONS: There were gender differences in mortality and risk
      factors; sex work and prison were gender specific risk factors. These factors
      should be investigated further to better design future preventive measures.

PMID- 24886465
TI  - Pharyngeal diameter in various head and neck positions during exercise in sport
      horses.
AB  - BACKGROUND: In equine athletes, dynamic stenotic disorders of the upper airways
      are often the cause for abnormal respiratory noises and/or poor performance.
      There are hypotheses, that head and neck flexion may influence the morphology and
      function of the upper airway and thus could even induce or deteriorate disorders
      of the upper respiratory tract. Especially the pharynx, without osseous or
      cartilaginous support is prone to changes in pressure and airflow during
      exercise. The objective of this study was to develop a method for measuring the
      pharyngeal diameter in horses during exercise, in order to analyse whether a
      change of head-neck position may have an impact on the pharyngeal diameter.
      RESULTS: Under the assumption that the width of the epiglottis remains constant
      in healthy horses, the newly developed method for calculating the pharyngeal
      diameter in horses during exercise is unsusceptible against changes of the
      viewing-angle and distance between the endoscope and the structures, which are to
      be assessed. The quotient of the width of the epiglottis and the perpendicular
      from a fixed point on the dorsal pharynx to the epiglottis could be used to
      determine the pharyngeal diameter. The percentage change of this quotient
      (pharynx-epiglottis-ratio; PE-ratio) in the unrestrained head-neck position
      against the reference position was significantly larger than that of any other
      combination of the head-neck positions investigated. A relation between the
      percentage change in PE-ratio and the degree of head and neck flexion could not
      be confirmed. CONCLUSIONS: It could be shown, that the pharyngeal diameter is
      reduced through the contact position implemented by the rider in comparison to
      the unrestrained head and neck position. An alteration of the pharyngeal diameter
      depending on the degree of head and neck flexion (represented by ground and
      withers angle) could not be confirmed.

PMID- 24886467
TI  - Study protocol--resilience in individuals and families coping with the impacts of
      alcohol related injuries in remote indigenous communities: a mixed method study.
AB  - BACKGROUND: Alcohol Management Plans (AMPs) were first implemented by the
      Queensland Government a decade ago (2002-03). In 2008, further stringent controls
      were implemented and alcohol was effectively prohibited in some of the affected
      remote Indigenous communities. With the Queensland Government currently reviewing
      AMPs, prohibitions may be lifted making alcohol readily available once more in
      these communities. As yet no work explores the impact of alcohol related injuries
      in relation to individual, family and community resilience in Indigenous
      Australians. A resilience model recognises individuals and families for their
      strengths rather than their deficits. By revealing how some individuals and
      families survive and thrive, new ways of working with families who need support
      may be identified and adopted. The research will explore in detail the long-term
      impact of this kind of injury on individuals, families and communities.
      METHODS/DESIGN: This project will use a sequential explanatory mixed method
      design. Four discrete Indigenous communities in Cape York, far north Queensland
      are included in this program of research, chosen because there is previous data
      available regarding injury and alcohol related injuries. Four sequential studies
      will be conducted in order to address the research questions and provide a rich
      description of the impact of alcohol related injuries and resilience in these
      populations. The time period January 2006 to December 2011 was chosen because it
      captures the three years before and three years after 2008 when tight alcohol
      restrictions were implemented in the four communities. DISCUSSION: Long term
      effects of the AMPs are as yet unknown and only fragmented attempts to look at
      the impact of injury related to alcohol have been conducted. A well-structured
      research program that explores the long-term impact of alcohol related injuries
      in these communities will help inform policy development to capture the current
      situation and so that appropriate benchmarking can occur.The project has been
      approved by the James Cook University Human Research Ethics Committee H5618 &
      H5241.

PMID- 24886466
TI  - Rescue of glucocorticoid-programmed adipocyte inflammation by omega-3 fatty acid
      supplementation in the rat.
AB  - BACKGROUND: Adverse fetal environments predispose offspring to pathologies
      associated with the metabolic syndrome. Previously we demonstrated that adult
      offspring of dexamethasone-treated mothers had elevated plasma insulin and pro
      inflammatory cytokines, effects prevented by a postnatal diet enriched with omega
      (n)-3 fatty acids. Here we tested whether prenatal glucocorticoid excess also
      programmed the adipose tissue phenotype, and whether this outcome is rescued by
      dietary n-3 fatty acids. METHODS: Offspring of control and dexamethasone-treated
      mothers (0.75 MUg/ml in drinking water, day 13 to term) were cross-fostered to
      mothers on a standard (Std) or high n-3 (Hn3) diet at birth. Offspring remained
      on these diets post-weaning, and serum and retroperitoneal fat were obtained at 6
      months of age (n = 5-8 per group). Serum was analysed for blood lipids and fatty
      acid profiles, adipocyte cross sectional area was measured by unbiased
      stereological analysis and adipose expression of markers of inflammation,
      glucocorticoid sensitivity and lipid metabolism were determined by RT-qPCR
      analysis. RESULTS: Serum total fatty acid levels were elevated (P < 0.01) in male
      offspring of dexamethasone-treated mothers, an effect prevented by Hn3
      consumption. Prenatal dexamethasone also programmed increased adipose expression
      of Il6, Il1b (both P < 0.05) and Tnfa (P < 0.001) mRNAs regardless of fetal sex,
      but again this effect was prevented (for Il6 and Il1b) by Hn3 consumption.
      Offspring of dexamethasone-treated mothers had increased adipose expression of Gr
      (P = 0.008) and Ppara (P < 0.05) regardless of sex or postnatal diet, while
      11bHsd1 was upregulated in males only. The Hn3 diet increased Ppard expression
      and reduced adipocyte size in all offspring (both P < 0.05) irrespective of
      prenatal treatment. CONCLUSIONS: Prenatal glucocorticoid exposure programmed
      increased expression of inflammatory markers and enhanced glucocorticoid
      sensitivity of adipose tissue. Partial prevention of this phenotype by high n-3
      consumption indicates that postnatal dietary manipulations can limit adverse
      fetal programming effects on adipose tissue.

PMID- 24886469
TI  - Unexpected angular or rotational deformity after corrective osteotomy.
AB  - BACKGROUND: Codman's paradox reveals a misunderstanding of geometry in orthopedic
      practice. Physicians often encounter situations that cannot be understood
      intuitively during orthopedic interventions such as corrective osteotomy.
      Occasionally, unexpected angular or rotational deformity occurs during
      surgery.This study aimed to draw the attention of orthopedic surgeons toward the
      concepts of orientation and rotation and demonstrate the potential for unexpected
      deformity after orthopedic interventions. This study focused on three situations:
      shoulder arthrodesis, femoral varization derotational osteotomy, and femoral
      derotation osteotomy. METHODS: First, a shoulder model was generated to calculate
      unexpected rotational deformity to demonstrate Codman's paradox. Second, femoral
      varization derotational osteotomy was simulated using a cylinder model. Third, a
      reconstructed femoral model was used to calculate unexpected angular or
      rotational deformity during femoral derotation osteotomy. RESULTS: Unexpected
      external rotation was found after forward elevation and abduction of the shoulder
      joint. In the varization and derotation model, closed-wedge osteotomy and
      additional derotation resulted in an unexpected extension and valgus deformity,
      namely, under-correction of coxa valga. After femoral derotational osteotomy,
      varization and extension of the distal fragment occurred, although the extension
      was negligible. CONCLUSIONS: Surgeons should be aware of unexpected angular
      deformity after surgical procedure involving bony areas. The degree of deformity
      differs depending on the context of the surgical procedure. However, this study
      reveals that notable deformities can be expected during orthopedic procedures
      such as femoral varization derotational osteotomy.

PMID- 24886470
TI  - A simple and feasible questionnaire to estimate menstrual blood loss:
      relationship with hematological and gynecological parameters in young women.
AB  - BACKGROUND: Menstrual blood loss (MBL) has been shown to be an important
      determinant in iron status, work performance and well-being. Several methods have
      been developed to estimate MBL, the standard quantitative method however has
      limited application in clinical practice as it is expensive and requires women to
      collect, store and submit their sanitary products for analysis. We therefore
      aimed to develop a MBL-score based on a questionnaire, and to validate it by
      several hematological and biochemical parameters in women of childbearing age.
      METHODS: A total of 165 healthy young women were recruited. Hematological
      (hematocrit, hemoglobin, erythrocyte, leucocyte and platelet counts) and iron
      status (serum iron, serum ferritin, serum transferrin, and total iron binding
      capacity) parameters were analyzed at baseline. Women were asked to fulfill two
      gynecological questionnaires: a general questionnaire, to inform about the
      volunteer's general menstrual characteristics; and a MBL questionnaire, to
      provide details of the duration of menstruation, number of heavy blood loss days,
      and number and type of pads and/or tampons used during the heaviest bleeding day,
      for all consecutive menstrual periods during 16 weeks. A MBL-score was calculated
      for each period and women, and its reliability determined by the Cronbach's alpha
      coefficient. Pearson's linear correlation tests were performed between blood
      parameters and the MBL-score. Two clusters were formed according the MBL-score
      (cluster 1: low MBL and cluster 2: high MBL). RESULTS: Significant higher MBL
      score was observed in women who reported having a history of anemia (p = 0.015),
      staining the bed at night during menstruation (p < 0.001) and suffering inter
      menstrual blood loss (p = 0.044), compared to those who did not. Women who used
      hormonal contraceptives presented lower MBL-scores than the others (p = 0.004).
      The MBL-score was negatively associated with log-ferritin (p = 0.006) and
      platelet count (p = 0.011). Women in cluster 1 presented higher ferritin (p =
      0.043) than women in cluster 2. CONCLUSIONS: We developed an easy and practical
      method for estimating menstrual blood loss based on a score calculated from a
      questionnaire in healthy women at childbearing age. The MBL-score is highly
      reliable and reflects menstrual blood loss validated by hematological and
      biochemical parameters.

PMID- 24886468
TI  - Retrospective checking of compliance with practice guidelines for acute stroke
      care: a novel experiment using openEHR's Guideline Definition Language.
AB  - BACKGROUND: Providing scalable clinical decision support (CDS) across
      institutions that use different electronic health record (EHR) systems has been a
      challenge for medical informatics researchers. The lack of commonly shared EHR
      models and terminology bindings has been recognised as a major barrier to sharing
      CDS content among different organisations. The openEHR Guideline Definition
      Language (GDL) expresses CDS content based on openEHR archetypes and can support
      any clinical terminologies or natural languages. Our aim was to explore in an
      experimental setting the practicability of GDL and its underlying archetype
      formalism. A further aim was to report on the artefacts produced by this new
      technological approach in this particular experiment. We modelled and
      automatically executed compliance checking rules from clinical practice
      guidelines for acute stroke care. METHODS: We extracted rules from the European
      clinical practice guidelines as well as from treatment contraindications for
      acute stroke care and represented them using GDL. Then we executed the rules
      retrospectively on 49 mock patient cases to check the cases' compliance with the
      guidelines, and manually validated the execution results. We used openEHR
      archetypes, GDL rules, the openEHR reference information model, reference
      terminologies and the Data Archetype Definition Language. We utilised the open
      sourced GDL Editor for authoring GDL rules, the international archetype
      repository for reusing archetypes, the open-sourced Ocean Archetype Editor for
      authoring or modifying archetypes and the CDS Workbench for executing GDL rules
      on patient data. RESULTS: We successfully represented clinical rules about 14 out
      of 19 contraindications for thrombolysis and other aspects of acute stroke care
      with 80 GDL rules. These rules are based on 14 reused international archetypes
      (one of which was modified), 2 newly created archetypes and 51 terminology
      bindings (to three terminologies). Our manual compliance checks for 49 mock
      patients were a complete match versus the automated compliance results.
      CONCLUSIONS: Shareable guideline knowledge for use in automated retrospective
      checking of guideline compliance may be achievable using GDL. Whether the same
      GDL rules can be used for at-the-point-of-care CDS remains unknown.

PMID- 24886471
TI  - Trends of Staphylococcus aureus bloodstream infections in a neonatal intensive
      care unit from 2000-2009.
AB  - BACKGROUND: Invasive methicillin-resistant Staphylococcus aureus (MRSA) and
      methicillin-sensitive Staphylococcus aureus (MSSA) infections are major causes of
      numerous neonatal intensive care unit (NICU) outbreaks. There have been
      increasing reports of MRSA outbreaks in various neonatal intensive care units
      (NICUs) over the last decade. Our objective was to review the experience of
      Staphylococcus aureus sepsis in our NICU in the last decade and describe the
      trends in the incidence of Staphylococcus aureus blood stream infections from
      2000 to 2009. METHODS: A retrospective perinatal database review of all neonates
      admitted to our NICU with blood cultures positive for Staphylococcus aureus from
      (Jan 1st 2000 to December 31st 2009) was conducted. Infants were identified from
      the database and data were collected regarding their clinical characteristics and
      co-morbidities, including shock with sepsis and mortality. Period A represents
      patients admitted in 2000-2003. Period B represents patients seen in 2004-2009.
      RESULTS: During the study period, 156/11111 infants were identified with
      Staphylococcus aureus blood stream infection: 41/4486 (0.91%) infants in Period A
      and 115/6625 (1.73%) in Period B (p < 0.0004). Mean gestation at birth was 26
      weeks for infants in both periods. There were more MRSA infections in Period B
      (24% vs. 55% p < 0.05) and they were associated with more severe outcomes. In
      comparing the cases of MRSA infections observed in the two periods, infants in
      period B notably had significantly more pneumonia cases (2.4% vs. 27%, p =
      0.0005) and a significantly higher mortality rate (0% vs. 15.7%, p = 0.0038). The
      incidences of skin and soft tissue infections and of necrotizing enterocolitis
      were not significantly changed in the two periods. CONCLUSION: There was an
      increase in the incidence of Staphylococcus aureus infection among neonates after
      2004. Although MSSA continues to be a problem in the NICU, MRSA infections were
      more prevalent in the past 6 years in our NICU. Increased severity of
      staphylococcal infections and associated rising mortality are possibly related to
      the increasing MRSA infections with a more virulent community-associated strain.

PMID- 24886472
TI  - Accounting for individual differences and timing of events: estimating the effect
      of treatment on criminal convictions in heroin users.
AB  - BACKGROUND: The reduction of crime is an important outcome of opioid maintenance
      treatment (OMT). Criminal intensity and treatment regimes vary among OMT
      patients, but this is rarely adjusted for in statistical analyses, which tend to
      focus on cohort incidence rates and rate ratios. The purpose of this work was to
      estimate the relationship between treatment and criminal convictions among OMT
      patients, adjusting for individual covariate information and timing of events,
      fitting time-to-event regression models of increasing complexity. METHODS:
      National criminal records were cross linked with treatment data on 3221 patients
      starting OMT in Norway 1997-2003. In addition to calculating cohort incidence
      rates, criminal convictions was modelled as a recurrent event dependent variable,
      and treatment a time-dependent covariate, in Cox proportional hazards, Aalen's
      additive hazards, and semi-parametric additive hazards regression models. Both
      fixed and dynamic covariates were included. RESULTS: During OMT, the number of
      days with criminal convictions for the cohort as a whole was 61% lower than when
      not in treatment. OMT was associated with reduced number of days with criminal
      convictions in all time-to-event regression models, but the hazard ratio (95% CI)
      was strongly attenuated when adjusting for covariates; from 0.40 (0.35, 0.45) in
      a univariate model to 0.79 (0.72, 0.87) in a fully adjusted model. The hazard was
      lower for females and decreasing with older age, while increasing with high
      numbers of criminal convictions prior to application to OMT (all p < 0.001). The
      strongest predictors were level of criminal activity prior to entering into OMT,
      and having a recent criminal conviction (both p < 0.001). The effect of several
      predictors was significantly time-varying with their effects diminishing over
      time. CONCLUSIONS: Analyzing complex observational data regarding to fixed
      factors only overlooks important temporal information, and naive cohort level
      incidence rates might result in biased estimates of the effect of interventions.
      Applying time-to-event regression models, properly adjusting for individual
      covariate information and timing of various events, allows for more precise and
      reliable effect estimates, as well as painting a more nuanced picture that can
      aid health care professionals and policy makers.

PMID- 24886473
TI  - Polymicrobial airway bacterial communities in adult bronchiectasis patients.
AB  - BACKGROUND: Chronic airway infection contributes to the underlying pathogenesis
      of non-cystic fibrosis bronchiectasis (NCFBr). In contrast to other chronic
      airway infections, associated with COPD and CF bronchiectasis, where
      polymicrobial communities have been implicated in lung damage due to the vicious
      circle of recurrent bacterial infections and inflammation, there is sparse
      information on the composition of bacterial communities in NCFBr. Seventy
      consecutive patients were recruited from an outpatient adult NCFBr clinic.
      Bacterial communities in sputum samples were analysed by culture and
      pyrosequencing approaches. Bacterial sequences were analysed using partial least
      square discrimination analyses to investigate trends in community composition and
      identify those taxa that contribute most to community variation. RESULTS: The
      lower airway in NCFBr is dominated by three bacterial taxa Pasteurellaceae,
      Streptococcaceae and Pseudomonadaceae. Moreover, the bacterial community is much
      more diverse than indicated by culture and contains significant numbers of other
      genera including anaerobic Prevotellaceae, Veillonellaceae and Actinomycetaceae.
      We found particular taxa are correlated with different clinical states, 27 taxa
      were associated with acute exacerbations, whereas 11 taxa correlated with stable
      clinical states. We were unable to demonstrate a significant effect of antibiotic
      therapy, gender, or lung function on the diversity of the bacterial community.
      However, presence of clinically significant culturable taxa; particularly
      Pseudomonas aeruginosa and Haemophilus influenzae correlated with a significant
      change in the diversity of the bacterial community in the lung. CONCLUSIONS: We
      have demonstrated that acute exacerbations, the frequency of exacerbation and
      episodes of clinical stability are correlated, in some patients, with a
      significantly different bacterial community structure, that are associated with a
      presence of particular taxa in the NCFBr lung. Moreover, there appears to be an
      inverse relationship between the abundance of P. aeruginosa and that of of H.
      influenzae within the NCFBr lung bacterial community. This interaction requires
      further exploration.

PMID- 24886474
TI  - Blood pressure level impacts risk of death among HIV seropositive adults in
      Kenya: a retrospective analysis of electronic health records.
AB  - BACKGROUND: Mortality among people with human immunodeficiency virus (HIV)
      infection is increasingly due to non-communicable causes. This has been observed
      mostly in developed countries and the routine care of HIV infected individuals
      has now expanded to include attention to cardiovascular risk factors.
      Cardiovascular risk factors such as high blood pressure are often overlooked
      among HIV seropositive (+) individuals in sub-Saharan Africa. We aimed to
      determine the effect of blood pressure on mortality among HIV+ adults in Kenya.
      METHODS: We performed a retrospective analysis of electronic medical records of a
      large HIV treatment program in western Kenya between 2005 and 2010. All included
      individuals were HIV+. We excluded participants with AIDS, who were <16 or >80
      years old, or had data out of acceptable ranges. Missing data for key covariates
      was addressed by inverse probability weighting. Primary outcome measures were
      crude mortality rate and mortality hazard ratio (HR) using Cox proportional
      hazards models adjusted for potential confounders including HIV stage. RESULTS:
      There were 49,475 (74% women) HIV+ individuals who met inclusion and exclusion
      criteria. Mortality rates for men and women were 3.8 and 1.8/100 person-years,
      respectively, and highest among those with the lowest blood pressures. Low blood
      pressure was associated with the highest mortality incidence rate (IR) (systolic
      <100 mmHg IR 5.2 [4.8-5.7]; diastolic <60 mmHg IR 9.2 [8.3-10.2]). Mortality rate
      among men with high systolic blood pressure without advanced HIV (3.0, 95% CI:
      1.6-5.5) was higher than men with normal systolic blood pressure (1.1, 95% CI:
      0.7-1.7). In weighted proportional hazards regression models, men without
      advanced HIV disease and systolic blood pressure >=140 mmHg carried a higher
      mortality risk than normotensive men (HR: 2.39, 95% CI: 0.94-6.08). CONCLUSIONS:
      Although there has been little attention paid to high blood pressure among HIV+
      Africans, we show that blood pressure level among HIV+ patients in Kenya is
      related to mortality. Low blood pressure carries the highest mortality risk. High
      systolic blood pressure is associated with mortality among patients whose disease
      is not advanced. Further investigation is needed into the cause of death for such
      patients.

PMID- 24886475
TI  - The Survivor Unmet Needs Survey (SUNS) for haematological cancer survivors: a
      cross-sectional study assessing the relevance and psychometric properties.
AB  - BACKGROUND: Relevant and psychometrically sound needs assessment tools are
      necessary for accurate assessment of haematological cancer survivors unmet needs.
      No previous study has developed nor psychometrically evaluated a comprehensive
      needs assessment tool for use with population-based samples of haematological
      cancer survivors. This study aimed to assess the validity and reliability of the
      Survivor Unmet Needs Survey (SUNS) with haematological cancer survivors. METHODS:
      The relevance, content and face validity of the SUNS to haematological cancer
      survivors was assessed using qualitative interviews. Psychometric evaluation was
      conducted using data collected from haematological cancer survivors, aged 18-80
      years at recruitment and recruited from four Australian cancer registries.
      Construct, convergent and discriminant validity; internal reliability and floor
      and ceiling effects were assessed. A second survey was completed by a sub-sample
      of survivors recruited from two of the four registries to assess test-retest
      reliability. RESULTS: Results from 17 qualitative interviews confirmed the
      relevance, face and content validity of the original items of the SUNS for use
      with haematological cancer survivors. Overall, 1,957 eligible haematological
      cancer survivors were contacted by the cancer registries. Of these 1,280 were
      sent a survey, and 715 returned a survey (37% of eligible survivors contacted and
      56% of survivors sent a survey). A total of 529 survivors completed all 89 items
      of the SUNS and were included in the exploratory factor analysis. Exploratory
      factor analysis supported the original five-factor structure of the SUNS.
      Evidence for convergent validity was established, with all five domains of the
      SUNS illustrating a moderate positive correlation with all three subscales of the
      Depression Anxiety and Stress Scale (DASS-21). All Cronbach's alpha values were
      above 0.9 and all corrected item-total correlations were acceptable (>0.2).
      Criteria for discriminant validity was not met, with only 10 of the 15 (67%) a
      priori hypotheses supported. Test-retest reliability was acceptable for 40 of the
      89 items (45%) and for three of the five domains. Significant floor effects were
      evident for all five domains. CONCLUSIONS: The SUNS demonstrates evidence for
      multiple features of validity and reliability as a measure of unmet needs for
      haematological cancer survivors. However, evidence supporting some psychometric
      properties was limited.

PMID- 24886476
TI  - Positive patient experiences in an Australian integrative oncology centre.
AB  - BACKGROUND: The purpose of this study was to explore the experiences of cancer
      patients' utilising complementary and integrative therapies (CIT) within
      integrative oncology centres across Western Australia. METHODS: Across four
      locations 135 patients accessed CIT services whilst undergoing outpatient medical
      treatment for cancer. Of the 135 patients, 66 (61+/-12 y; female n=45; male n=21)
      agreed to complete a personal accounts questionnaire consisting of open-ended
      questions designed to explore patients' perceptions of CIT. All results were
      transcribed into nVivo (v9) and using thematic analysis, key themes were
      identified. RESULTS: Of the 66 participants, 100% indicated they would "recommend
      complementary therapies to other patients" and 92% stated "CIT would play a
      significant role in their future lifestyle". A mean score of 8+/-1 indicated an
      improvement in participants' perception of wellbeing following a CIT session.
      Three central themes were identified: empowerment, support and relaxation.
      Fourteen sub-themes were identified, with all themes clustered into a framework
      of multifaceted views held by cancer patients in relation to wellbeing, role of
      significant others and control. CONCLUSIONS: Exploration of patients' experiences
      reveals uniformly positive results. One of the key merits of the environment
      created within the centres is patients are able to work through their cancer
      journey with an increased sense of empowerment, without placing them in
      opposition to conventional medical treatment. In order to effectively target
      integrative support services it is crucial to explore the experiences of patients
      in their own words and use those forms of expression to drive service delivery.

PMID- 24886477
TI  - Local effect of stereotactic body radiotherapy for primary and metastatic liver
      tumors in 130 Japanese patients.
AB  - BACKGROUND AND AIMS: Stereotactic body radiotherapy (SBRT) is a relatively new
      treatment for liver tumor. The outcomes of SBRT for liver tumor unfit for
      ablation and surgical resection were evaluated. METHODS: Liver tumor patients
      treated with SBRT in seven Japanese institutions were studied retrospectively.
      Patients given SBRT for liver tumor between 2004 and 2012 were collected.
      Patients treated with SBRT preceded by trans-arterial chemoembolization (TACE)
      were eligible. Seventy-nine patients with hepatocellular carcinoma (HCC) and 51
      patients with metastatic liver tumor were collected. The median biologically
      effective dose (BED) (alpha/beta = 10 Gy) was 96.3 Gy for patients with HCC and
      105.6 Gy with metastatic liver tumor. RESULTS: The median follow-up time was
      475.5 days in patients with HCC and 212.5 days with metastatic liver tumor. The 2
      year local control rate (LCR) for HCC and metastatic liver tumor was 74.8% +/-
      6.3% and 64.2 +/- 9.5% (p = 0.44). The LCR was not different between BED10 >= 100
      Gy and < 100 Gy (p = 0.61). The LCR was significantly different between maximum
      tumor diameter > 30 mm vs. <= 30 mm (64% vs. 85%, p = 0.040) in all 130 patients.
      No grade 3 laboratory toxicities in the acute, sub-acute and chronic phases were
      observed. CONCLUSIONS: There was no difference in local control after SBRT in the
      range of median BED10 around 100 Gy for between HCC and metastatic liver tumor.
      SBRT is safe and might be an alternative method to resection and ablation.
      SUMMARY: There was no difference in local control after SBRT in the range of
      median BED10 around 100 Gy for between HCC and metastatic liver tumor and SBRT is
      safe and might be an alternative method to resection and ablation.

PMID- 24886478
TI  - Epidemiology of the avian influenza A (H7N9) outbreak in Zhejiang Province,
      China.
AB  - BACKGROUND: A novel influenza A virus infection was identified on March 31, 2013
      in China and a total of 134 cases were identified in 12 provinces of China
      between March 25 and September 31, 2013. Of these, 46 cases occurred in Zhejiang
      Province and the number of patients is the largest in China. METHODS: Field
      investigations were conducted for each confirmed H7N9 case. A standardized
      questionnaire was used to collect information about demographics, exposure
      history, clinical signs and symptoms, timelines of medical visits and care after
      onset of illness, and close contacts. Descriptive statistics were used to analyze
      the epidemiological and clinical characteristics. Samples from the patients were
      collected and tested by real time reverse transcriptase-polymerase chain reaction
      and viral culture. RESULTS: A total of 46 laboratory confirmed cases of H7N9
      influenza infection were identified in the Zhejiang province between March 31 and
      September 31, 2013 of which 29 were male and 17 were female. The median age of
      patients was 61.5 years and 76.09% of cases occurred in persons aged >=50 years
      old. Unlike other province, 34.78% of cases in Zhejiang Province were rural
      residents. Among 11 deaths, 9 were male, 10 were older than 60 years old, and 10
      had underlying diseases. 30 of 38 cases with available data had a recent history
      of poultry exposures and 8 cases had multi-exposure history. The estimated median
      incubation period was two days which was shorter than corresponding data in other
      provinces. All cases were hospitalized and the median time from illness onset to
      hospitalization was 5 days. Symptoms at the onset of the illness included fever,
      cough, expectoration, shivering, fatigue, muscular aches, nausea, vomiting. Only
      4.91% contacts developed respiratory symptoms, but their samples were tested
      negative for H7N9 virus designating lack of human-to-human transmission of the
      virus. CONCLUSIONS: All cases were sporadic and there was no evidence of an
      epidemiologic link between them. Control measures including closing affected
      poultry and slaughtering backyard poultry are needed not only in urban areas but
      also in rural areas to reduce human H7N9 infection risk.

PMID- 24886482
TI  - Transfer to hospital in planned home births: a systematic review.
AB  - BACKGROUND: There is concern about the safety of homebirths, especially in women
      transferred to hospital during or after labour. The scope of transfer in planned
      home births has not been assessed in a systematic review. This review aimed to
      describe the proportions and indications for transfer from home to hospital
      during or after labour in planned home births. METHODS: The databases Pubmed,
      Embase, Cinahl, Svemed+, and the Cochrane Library were searched using the MeSH
      term "home childbirth". Inclusion criteria were as follows: the study population
      was women who chose planned home birth at the onset of labour; the studies were
      from Western countries; the birth attendant was an authorised midwife or medical
      doctor; the studies were published in 1985 or later, with data not older than
      from 1980; and data on transfer from home to hospital were described. Of the 3366
      titles identified, 83 full text articles were screened, and 15 met the inclusion
      criteria. Two of the authors independently extracted the data. Because of the
      heterogeneity and lack of robustness across the studies, there were considerable
      risks for bias if performing meta-analyses. A descriptive presentation of the
      findings was chosen. RESULTS: Fifteen studies were eligible for inclusion,
      containing data from 215,257 women. The total proportion of transfer from home to
      hospital varied from 9.9% to 31.9% across the studies. The most common indication
      for transfer was labour dystocia, occurring in 5.1% to 9.8% of all women planning
      for home births. Transfer for indication for foetal distress varied from 1.0% to
      3.6%, postpartum haemorrhage from 0% to 0.2% and respiratory problems in the
      infant from 0.3% to 1.4%. The proportion of emergency transfers varied from 0% to
      5.4%. CONCLUSION: Future studies should report indications for transfer from home
      to hospital and provide clear definitions of emergency transfers.

PMID- 24886480
TI  - Genome analysis reveals three genomospecies in Mycobacterium abscessus.
AB  - BACKGROUND: Mycobacterium abscessus complex, the third most frequent
      mycobacterial complex responsible for community- and health care-associated
      infections in developed countries, comprises of M. abscessus subsp. abscessus and
      M. abscessus subsp. bolletii reviously referred as Mycobacterium bolletii and
      Mycobacterium massiliense. The diversity of this group of opportunistic pathogens
      is poorly described. RESULTS: In-depth analysis of 14 published M. abscessus
      complex genomes found a pan-genome of 6,153 proteins and core-genome of 3,947
      (64.1%) proteins, indicating a non-conservative genome. Analysing the average
      percentage of amino-acid sequence identity (from 94.19% to 98.58%) discriminates
      three main clusters C1, C2 and C3: C1 comprises strains belonging to M.
      abscessus, C2 comprises strains belonging to M. massiliense and C3 comprises
      strains belonging to M. bolletii; and two sub-clusters in clusters C2 and C3. The
      phylogenomic network confirms these three clusters. The genome length (from 4.8
      to 5.51-Mb) varies from 5.07-Mb in C1, 4.89-Mb in C2A, 5.01-Mb in C2B and 5.28-Mb
      in C3. The mean number of prophage regions (from 0 to 7) is 2 in C1; 1.33 in C2A;
      3.5 in C2B and five in C3. A total of 36 genes are uniquely present in C1, 15 in
      C2 and 15 in C3. These genes could be used for the detection and identification
      of organisms in each cluster. Further, the mean number of host-interaction
      factors (including PE, PPE, LpqH, MCE, Yrbe and type VII secretion system ESX3
      and ESX4) varies from 70 in cluster C1, 80 in cluster C2A, 74 in cluster C2B and
      93 in clusters C3A and C3B. No significant differences in antibiotic resistance
      genes were observed between clusters, in contrast to previously reported in-vitro
      patterns of drug resistance. They encode both penicillin-binding proteins
      targeted by beta-lactam antibiotics and an Ambler class A beta-lactamase for
      which inhibitors exist. CONCLUSIONS: Our comparative analysis indicates that M.
      abscessus complex comprises three genomospecies, corresponding to M. abscessus,
      M. bolletii, and M. massiliense. The genomics data here reported indicate
      differences in virulence of medical interest; and suggest targets for the refined
      detection and identification of M. abscessus.

PMID- 24886479
TI  - Novel principles of gamma-retroviral insertional transcription activation in
      murine leukemia virus-induced end-stage tumors.
AB  - BACKGROUND: Insertional mutagenesis screens of retrovirus-induced mouse tumors
      have proven valuable in human cancer research and for understanding adverse
      effects of retroviral-based gene therapies. In previous studies, the assignment
      of mouse genes to individual retroviral integration sites has been based on close
      proximity and expression patterns of annotated genes at target positions in the
      genome. We here employed next-generation RNA sequencing to map retroviral-mouse
      chimeric junctions genome-wide, and to identify local patterns of transcription
      activation in T-lymphomas induced by the murine leukemia gamma-retrovirus SL3-3.
      Moreover, to determine epigenetic integration preferences underlying long-range
      gene activation by retroviruses, the colocalization propensity with common
      epigenetic enhancer markers (H3K4Me1 and H3K27Ac) of 6,117 integrations derived
      from end-stage tumors of more than 2,000 mice was examined. RESULTS: We detected
      several novel mechanisms of retroviral insertional mutagenesis: bidirectional
      activation of mouse transcripts on opposite sides of a provirus including
      transcription of unannotated mouse sequence; sense/antisense-type activation of
      genes located on opposite DNA strands; tandem-type activation of distal genes
      that are positioned adjacently on the same DNA strand; activation of genes that
      are not the direct integration targets; combination-type insertional mutagenesis,
      in which enhancer activation, alternative chimeric splicing and retroviral
      promoter insertion are induced by a single retrovirus. We also show that
      irrespective of the distance to transcription start sites, the far majority of
      retroviruses in end-stage tumors colocalize with H3K4Me1 and H3K27Ac-enriched
      regions in murine lymphoid tissues. CONCLUSIONS: We expose novel retrovirus
      induced host transcription activation patterns that reach beyond a single and
      nearest annotated gene target. Awareness of this previously undescribed layer of
      complexity may prove important for elucidation of adverse effects in retroviral
      based gene therapies. We also show that wild-type gamma-retroviruses are
      frequently positioned at enhancers, suggesting that integration into regulatory
      regions is specific and also subject to positive selection for sustaining long
      range gene activation in end-stage tumors. Altogether, this study should prove
      useful for extrapolating adverse outcomes of retroviral vector therapies, and for
      understanding fundamental cellular regulatory principles and retroviral biology.

PMID- 24886481
TI  - The interplay between seasonality and density: consequences for female breeding
      decisions in a small cyclic herbivore.
AB  - BACKGROUND: Cyclic rodent population dynamics are subjected to both intrinsic
      regulatory processes such as density-dependence and extrinsic environmental
      forcing. Among extrinsic factors, seasonal environmental variation is understood
      to facilitate cycles. In rodents, these processes have been studied mostly
      independently and their relative importance for population dynamics is poorly
      known. RESULTS: We performed a detailed analysis of common vole (Microtus
      arvalis) reproduction in a cyclic population using a spatially extensive data set
      over 17 years in central-western France. Environmental seasonality was the main
      source of explained variation in common vole reproduction. Additionally, inter
      annual variation in the environment explained a smaller part of the variance in
      reproduction in spring and summer than in winter, whereas the effect of density
      was only found in autumn and winter. In particular, we detected a strong impact
      of plant productivity on fecundity during the breeding season, with low
      vegetation productivity being able to bring vole reproduction nearly to a halt.
      In contrast, vole reproduction during autumn and winter was mainly shaped by
      intrinsic factors, with only the longer and heavier females being able to
      reproduce. The effect of population density on reproduction was negative,
      mediated by direct negative effects on the proportion of breeders in autumn and
      winter during outbreak years and by a delayed negative effect on litter size the
      following year. CONCLUSIONS: During the main breeding season, variability of
      female vole reproduction is predominantly shaped by food resources, suggesting
      that only highly productive environment may induce vole outbreaks. During fall
      and winter, variability of female vole reproduction is mainly controlled by
      intrinsic factors, with high population density suppressing reproduction. This
      suggests, in this cyclic population, that negative direct density dependence on
      reproduction could explain winter declines after outbreaks.

PMID- 24886484
TI  - Models in biology: 'accurate descriptions of our pathetic thinking'.
AB  - In this essay I will sketch some ideas for how to think about models in biology.
      I will begin by trying to dispel the myth that quantitative modeling is somehow
      foreign to biology. I will then point out the distinction between forward and
      reverse modeling and focus thereafter on the former. Instead of going into
      mathematical technicalities about different varieties of models, I will focus on
      their logical structure, in terms of assumptions and conclusions. A model is a
      logical machine for deducing the latter from the former. If the model is correct,
      then, if you believe its assumptions, you must, as a matter of logic, also
      believe its conclusions. This leads to consideration of the assumptions
      underlying models. If these are based on fundamental physical laws, then it may
      be reasonable to treat the model as 'predictive', in the sense that it is not
      subject to falsification and we can rely on its conclusions. However, at the
      molecular level, models are more often derived from phenomenology and guesswork.
      In this case, the model is a test of its assumptions and must be falsifiable. I
      will discuss three models from this perspective, each of which yields biological
      insights, and this will lead to some guidelines for prospective model builders.

PMID- 24886483
TI  - A novel motif in the NaTrxh N-terminus promotes its secretion, whereas the C
      terminus participates in its interaction with S-RNase in vitro.
AB  - BACKGROUND: NaTrxh, a thioredoxin type h, shows differential expression between
      self-incompatible and self-compatible Nicotiana species. NaTrxh interacts in
      vitro with S-RNase and co-localizes with it in the extracellular matrix of the
      stylar transmitting tissue. NaTrxh contains N- and C-terminal extensions, a
      feature shared by thioredoxin h proteins of subgroup 2. To ascertain the function
      of these extensions in NaTrxh secretion and protein-protein interaction, we
      performed a deletion analysis on NaTrxh and fused the resulting variants to GFP.
      RESULTS: We found an internal domain in the N-terminal extension, called Nbeta,
      that is essential for NaTrxh secretion but is not hydrophobic, a canonical
      feature of a signal peptide. The lack of hydrophobicity as well as the location
      of the secretion signal within the NaTrxh primary structure, suggest an
      unorthodox secretion route for NaTrxh. Notably, we found that the fusion protein
      NaTrxh-GFP(KDEL) is retained in the endoplasmic reticulum and that treatment of
      NaTrxh-GFP-expressing cells with Brefeldin A leads to its retention in the Golgi,
      which indicates that NaTrxh uses, to some extent, the endoplasmic reticulum and
      Golgi apparatus for secretion. Furthermore, we found that Nbeta contributes to
      NaTrxh tertiary structure stabilization and that the C-terminus functions in the
      protein-protein interaction with S-RNase. CONCLUSIONS: The extensions contained
      in NaTrxh sequence have specific functions on the protein. While the C-terminus
      directly participates in protein-protein interaction, particularly on its
      interaction with S-RNase in vitro; the N-terminal extension contains two
      structurally different motifs: Nalpha and Nbeta. Nbeta, the inner domain (Ala-17
      to Pro-27), is essential and enough to target NaTrxh towards the apoplast.
      Interestingly, when it was fused to GFP, this protein was also found in the cell
      wall of the onion cells. Although the biochemical features of the N-terminus
      suggested a non-classical secretion pathway, our results provided evidence that
      NaTrxh at least uses the endoplasmic reticulum, Golgi apparatus and also vesicles
      for secretion. Therefore, the Nbeta domain sequence is suggested to be a novel
      signal peptide.

PMID- 24886486
TI  - Ultrasound guidance reduces pneumothorax rate and improves safety of
      thoracentesis in malignant pleural effusion: report on 445 consecutive patients
      with advanced cancer.
AB  - BACKGROUND: Malignant pleural effusion (MPE) is an extremely common problem
      affecting cancer patients, and thoracentesis is an essential procedure in an
      attempt to delineate the etiology of the fluid collections and to relieve
      symptoms in affected patients. One of the most common complications of
      thoracentesis is pneumothorax, which has been reported to occur in 20% to 39% of
      thoracenteses, with 15% to 50% of patients with pneumothorax requiring tube
      thoracostomy.The present study was carried out to assess whether thoracenteses in
      cancer patients performed with ultrasound (US) guidance are associated with a
      lower rates of pneumothorax and tube thoracostomy than those performed without US
      guidance. METHODS: A total of 445 patients were recruited in this retrospective
      study. The medical records of 445 consecutive patients with cancer and MPE
      evaluable for this study, undergoing thoracentesis at the Oncology-Hematology and
      Internal Medicine Departments, Piacenza Hospital (Italy) were reviewed. RESULTS:
      From January 2005 to December 2011, in 310 patients (69.66%) thoracentesis was
      performed with US guidance and in 135 (30.34%) without it. On post-thoracentesis
      imaging performed in all these cases, 15 pneumothoraces (3.37%) were found; three
      of them (20%) required tube thoracostomy. Pneumothorax occurred in three out of
      310 procedures (0.97%) performed with US guidance and in 12 of 135 procedures
      (8.89%) performed without it (P<0.0001). It must be emphasized that in all three
      patients with pneumothorax requiring tube thoracostomy, thoracentesis was
      performed without US guidance. CONCLUSIONS: The routine use of US guidance during
      thoracentesis drastically reduces the rate of pneumothorax and tube thoracostomy
      in oncological patients, thus improving safety as demonstrated in this study.

PMID- 24886485
TI  - Immunotherapy of hepatocellular carcinoma with small double-stranded RNA.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies
      worldwide with limited therapeutic options. Since HCC has been shown to be
      immunogenic, immunotherapy is considered a promising therapeutic approach. Small
      interfering RNAs (siRNAs), depending on their structure and sequence, can trigger
      the innate immune system, which can potentially enhance the adaptive anticancer
      immune response in the tumor-bearing subjects. Immunostimulatory properties of
      nucleic acids can be applied to develop adjuvants for HCC treatment. METHODS: The
      transplantable HCC G-29 tumor in male CBA/LacSto (CBA) mice was used to study the
      effects of immunostimulatory RNA on tumor growth. Tumor size, metastases area in
      different organs of mice and mouse survival rate were analyzed. Furthermore the
      mouse serum IFN-alpha levels were measured using ELISA. RESULTS: In the present
      study, we found that a 19-bp RNA duplex (ImmunoStimulattory RNA or isRNA) with 3
      nt overhangs at the 3'-ends of specific sequence displays immunostimulatory,
      antitumor, and antimetastatic activities in mice bearing HCC G-29. Our results
      demonstrate that isRNA strongly increases the level of interferon-alpha (IFN
      alpha) by up to 25-fold relative to the level in mice injected with Lipofectamine
      alone (Mock), and to a lesser extent increases the level of proinflammatory
      cytokine interleukin-6 (IL-6) (by up to 5.5-fold relative to the Mock level), in
      mice blood serum. We showed that isRNA reliably (P < 0.05) inhibits primary tumor
      growth in mice compared to the mock group. Furthermore, injections of isRNA
      significantly enhanced necrotic processes in the center of the primary tumor, and
      decreased by twofold the width of the undifferentiated peripheral zone and the
      number of mitotic cells in this zone. The results showed that isRNA efficiently
      reduces the area of metastases in the liver, kidneys, and heart of CBA/LacSto
      mice with HCC. CONCLUSIONS: The obtained results clearly demonstrate
      immunostimulatory and antimetastatic properties of the isRNAs in mice with HCC.
      Consequently, this short double-stranded RNA can be considered as a potential
      adjuvant for the therapy of HCC.

PMID- 24886487
TI  - Outcome of surgical management for rhegmatogenous retinal detachment in Behcet's
      disease.
AB  - BACKGROUND: The purpose of the current study is to evaluate the surgical outcome
      for rhegmatogenous retinal detachment (RD) associated with Behcet's disease (BD).
      METHODS: The current retrospective study included all patients operated for
      rhegmatogenous RD associated with BD in our institution from June 2007 to June
      2012. Surgical repair was done either by scleral buckling (SB) or pars plana
      vitrectomy (PPV) according to the topography and clinical criteria of the
      detachment. RESULTS: The current study included 7 eyes of 7 patients (6 males and
      one female). The mean age was 34.3 +/- 4.9 years and all patients showed systemic
      features of BD. In 3 eyes, intravitreal triamcinolone acetonide (IVTA) was
      injected within 8 weeks prior to the occurrence of rhegmatogenous RD. Five eyes
      were treated with SB (segmental buckle in 4 cases and encircling buckle in one
      case) and 2 cases were treated by PPV. One case was initially treated by SB but
      showed recurrence of RD which was surgically repaired by PPV with successful
      closure of the retinal break. The retina was successfully reattached in all cases
      at the end of follow up period (22.0 +/- 6.7 months). CONCLUSIONS: Rhegmatogenous
      RD in BD can be effectively treated by scleral buckling in selected cases and PPV
      in more complex cases. Intravitreal injections may be a precipitating factor for
      rhegmatogenous RD.

PMID- 24886488
TI  - Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D)
      trial-a multi-centre, prospective, randomised, open, blinded end-point, 36-month
      study of 2,616 patients within primary care with stage 3b chronic kidney disease
      to compare the efficacy of spironolactone 25 mg once daily in addition to routine
      care on mortality and cardiovascular outcomes versus routine care alone: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common and increasing in prevalence.
      Cardiovascular disease (CVD) is a major cause of morbidity and death in CKD,
      though of a different phenotype to the general CVD population. Few therapies have
      proved effective in modifying the increased CVD risk or rate of renal decline in
      CKD. There are accumulating data that aldosterone receptor antagonists (ARA) may
      offer cardio-protection and delay renal impairment in patients with the CV
      phenotype in CKD. The use of ARA in CKD has therefore been increasingly
      advocated. However, no large study of ARA with renal or CVD outcomes is underway.
      METHODS: The study is a prospective randomised open blinded endpoint (PROBE)
      trial set in primary care where patients will mainly be identified by their GPs
      or from existing CKD lists. They will be invited if they have been formally
      diagnosed with CKD stage 3b or there is evidence of stage 3b CKD from blood
      results (eGFR 30-44 mL/min/1.73 m2) and fulfil the other inclusion/exclusion
      criteria. Patients will be randomised to either spironolactone 25 mg once daily
      in addition to routine care or routine care alone and followed-up for 36 months.
      DISCUSSION: BARACK D is a PROBE trial to determine the effect of ARA on mortality
      and cardiovascular outcomes (onset or progression of CVD) in patients with stage
      3b CKD. TRIAL REGISTRATION: EudraCT: 2012-002672-13ISRTN: ISRCTN44522369.

PMID- 24886489
TI  - Evaluation of partnerships in a transnational family violence prevention network
      using an integrated knowledge translation and exchange model: a mixed methods
      study.
AB  - BACKGROUND: Family violence is a significant and complex public health problem
      that demands collaboration between researchers, practitioners, and policymakers
      for systemic, sustainable solutions. An integrated knowledge translation network
      was developed to support joint research production and application in the area.
      The purpose of this study was to determine the extent to which the international
      Preventing Violence Across the Lifespan (PreVAiL) Research Network built
      effective partnerships among its members, with a focus on the knowledge user
      partner perspective. METHODS: This mixed-methods study employed a combination of
      questionnaire and semi-structured interviews to understand partnerships two years
      after PreVAiL's inception. The questionnaire examined communication,
      collaborative research, dissemination of research, research findings,
      negotiation, partnership enhancement, information needs, rapport, and commitment.
      The interviews elicited feedback about partners' experiences with being part of
      the network. RESULTS: Five main findings were highlighted: i) knowledge user
      partner involvement varied across activities, ranging from 11% to 79%
      participation rates; ii) partners and researchers generally converged on their
      assessment of communication indicators; iii) partners valued the network at both
      an individual level and to fulfill their organizations' mandates; iv) being part
      of PreVAiL allowed partners to readily contact researchers, and partners felt
      comfortable acting as an intermediary between PreVAiL and the rest of their own
      organization; v) application of research was just emerging; partners needed more
      actionable insights to determine ways to move forward given the research at that
      point in time. CONCLUSIONS: Our results demonstrate the importance of developing
      and nurturing strong partnerships for integrated knowledge translation. Our
      findings are applicable to other network-oriented partnerships where a diversity
      of stakeholders work to address complex, multi-faceted public health problems.

PMID- 24886490
TI  - Impact of Quebec's healthcare reforms on the organization of primary healthcare
      (PHC): a 2003-2010 follow-up.
AB  - BACKGROUND: Healthcare reforms initiated in the early 2000s in Quebec involved
      the implementation of new modes of primary healthcare (PHC) delivery and the
      creation of Health and Social Services Centers (HSSCs) to support it. The
      objective of this article is to assess and explain the degree of PHC
      organizational change achieved following these reforms. METHODS: We conducted two
      surveys of PHC organizations, in 2005 and 2010, in two regions of the province of
      Quebec, Canada. From the responses to these surveys, we derived a measure of
      organizational change based on an index of conformity to an ideal type (ICIT).
      One set of explanatory variables was contextual, related to coercive, normative
      and mimetic influences; the other consisted of organizational variables that
      measured receptivity towards new PHC models. Multilevel analyses were performed
      to examine the relationships between ICIT change in the post-reform period and
      the explanatory variables. RESULTS: Positive results were attained, as expressed
      by increase in the ICIT score in the post-reform period, mainly due to
      implementation of new types of PHC organizations (Family Medicine Groups and
      Network Clinics). Organizational receptivity was the main explanatory variable
      mediating the effect of coercive and mimetic influences. Normative influence was
      not a significant factor in explaining changes. CONCLUSION: Changes were modest
      at the system level but important with regard to new forms of PHC organizations.
      The top-down decreed reform was a determining factor in initiating change whereas
      local coercive and normative influences did not play a major role. The exemplar
      role played by certain PHC organizations through mimetic influence was more
      important. Receptivity of individual organizations was both a necessary condition
      and a mediating factor in influencing change. This supports the view that a
      combination of top-down and bottom-up strategy is best suited for achieving
      substantial changes in PHC local organization.

PMID- 24886491
TI  - Differences in muscle activity during hand-dexterity tasks between women with
      arthritis and a healthy reference group.
AB  - BACKGROUND: Impaired hand function is common in patients with arthritis and it
      affects performance of daily activities; thus, hand exercises are recommended.
      There is little information on the extent to which the disease affects activation
      of the flexor and extensor muscles during these hand-dexterity tasks. The purpose
      of this study was to compare muscle activation during such tasks in subjects with
      arthritis and in a healthy reference group. METHODS: Muscle activation was
      measured in m. extensor digitorium communis (EDC) and in m. flexor carpi radialis
      (FCR) with surface electromyography (EMG) in women with rheumatoid arthritis (RA,
      n = 20), hand osteoarthritis (HOA, n = 16) and in a healthy reference group (n =
      20) during the performance of four daily activity tasks and four hand exercises.
      Maximal voluntary isometric contraction (MVIC) was measured to enable
      intermuscular comparisons, and muscle activation is presented as %MVIC. RESULTS:
      The arthritis group used a higher %MVIC than the reference group in both FCR and
      EDC when cutting with a pair of scissors, pulling up a zipper and-for the EDC
      also when writing with a pen and using a key (p < 0.02). The exercise "rolling
      dough with flat hands" required the lowest %MVIC and may be less effective in
      improving muscle strength. CONCLUSIONS: Women with arthritis tend to use higher
      levels of muscle activation in daily tasks than healthy women, and wrist
      extensors and flexors appear to be equally affected. It is important that hand
      training programs reflect real-life situations and focus also on extensor
      strength.

PMID- 24886492
TI  - Subsets of regulatory T cells and their roles in allergy.
AB  - In recent years, it is recognized that acquired immunity is controlled by
      regulatory T cell (Treg). Since fundamental pathophysiological changes of allergy
      are mainly caused by hyperresponsiveness of immune system to allergens that
      acquires after birth, Tregs likely play key roles in the pathogenesis of allergy,
      particularly during the sensitization phase. However, accumulated information
      indicate that there are several distinctive subtypes of Tregs in man, and each of
      them seems to play different role in controlling immune system, which complicates
      the involvement of Tregs in allergy. The aim of the present study is to attempt
      to classify subtypes of Tregs and summarize their roles in allergy. Tregs should
      include natural Tregs (nTreg) including inducible costimulator (ICOS)(+) Tregs,
      inducible/adaptive Tregs (iTreg), interleukin (IL)-10-producing type 1 Tregs (Tr1
      cells), CD8(+) Tregs and IL-17-producing Tregs. These cells share some common
      features including expression of Foxp3 (except for Tr1 cells), and secretion of
      inhibitory cytokine IL-10 and/or TGF-beta. Furthermore, it is noticeable that
      Tregs likely contribute to allergic disorders such as dermatitis and airway
      inflammation, and play a crucial role in the treatment of allergy through their
      actions on suppression of effector T cells and inhibition of activation of mast
      cells and basophils. Modulation of functions of Tregs may provide a novel
      strategy to prevent and treat allergic diseases. 

PMID- 24886493
TI  - An open debate about the object and purpose of global health knowledge in the
      context of an interdisciplinary research partnership on HIV/STI prevention
      priorities in Peru.
AB  - BACKGROUND: With the failure of the latest vaccine trial, HVTN-505, HIV
      prevention efforts remain critical. Social and structural factors contributing to
      HIV and STI transmission include stigma regarding sexual violence, HIV infection
      and sexual orientation. For instance, HIV prevention and overall sexual health
      programs in Peru have been implemented yet key populations of youth (sex workers,
      male and transgender youth) continue to be overrepresented in new cases of HIV
      and STI. This suggests that interventions must take new directions and highlights
      the need for additional research. DISCUSSION: While interdisciplinary,
      international research collaborations often are indicated as best practice in
      developing new knowledge in global health and an important component of the
      leadership in health systems, this does not mean they are free of challenges. In
      this debate we document our reflections on some of the challenges in developing
      an interdisciplinary and international research team to understand HIV and STI
      prevention priorities among youth in two culturally diverse cities in Peru: Lima,
      the capital city, and Ayacucho, in the Andean region. SUMMARY: Rather than
      offering solutions we aim to contribute to the debate about the object and
      purpose of global health research in the context of developing international
      research partnerships that genuinely promote a reciprocal and bidirectional flow
      of knowledge between the Global South and the Global North, and researchers at
      intersections of these locations.

PMID- 24886494
TI  - Association of Egr3 genetic polymorphisms and coronary artery disease in the
      Uygur and Han of China.
AB  - BACKGROUND: Endothelial cell activation and dysfunction are the foundation of
      atherosclerosis, including coronary artery disease (CAD). Endothelial cell
      activation is mediated by the level of gene transcription. Early growth response
      3 (Egr3) is a critical determinant of vascular endothelial growth factor (VEGF)
      signalling in activated endothelial cells. If endothelial cells are excessively
      activated, it may lead to vasculopathic diseases, such as pathologic
      angiogenesis, inflammation, and atherosclerosis. The aim of the present study was
      to assess the association between the Egr3 gene polymorphisms and CAD. METHODS:
      Two independent case-control studies that involved the Han group (409 CAD
      patients and 351 control subjects) and the Uygur group (299 CAD patients and 303
      control subjects) analysed the relationship between Egr3 SNPs (rs1996147 and
      rs1008949) and CAD. Genotyping was undertaken using the TaqMan SNP genotyping
      assay. RESULTS: The entire Uygur group and the males in the Uygur group showed a
      higher frequency of the A allele (rs1996147) in CAD patients than in the control
      subjects (P = 0.003 and P = 0.005, respectively). Additionally, the distribution
      of the recessive model of rs1996147 (AA vs GG + AG) for the total sample and the
      males was significantly different between CAD patients and control participants
      (P = 0.002 and P = 0.003, respectively), and the difference remained
      statistically significant following multivariate adjustment (Total: OR = 1.705;
      95% CI: 1.166-2.494, P = 0.006; males: OR = 1.908, 95% CI: 1.189-3.062, P =
      0.007). However, for Uygur females, we did not observe a difference in the allele
      frequency or genotypic distribution of rs1996147 between CAD patients and control
      participants. Similarly, the distribution of the rs1996147 allele frequency or
      genotypes showed no significant difference between patients with CAD and control
      participants in the Han group. The distribution of rs1008949 genotypes, dominant
      model, recessive model, and allele frequency did not show a significant
      difference between patients with CAD and the control subjects in the Han and
      Uygur groups. CONCLUSION: rs1996147 may be a novel polymorphism of the Egr3 gene
      associated with CAD in males of the Chinese Uygur population.

PMID- 24886495
TI  - Brain areas involved in the acupuncture treatment of AD model rats: a PET study.
AB  - BACKGROUND: Acupuncture may effectively treat certain symptoms of Alzheimer's
      disease (AD). Although several studies have used functional brain imaging to
      investigate the mechanisms of acupuncture treatment on AD, these mechanisms are
      still poorly understood. We therefore further explored the mechanism by which
      needling at ST36 may have a therapeutic effect in a rat AD model. METHODS: A
      total of 80 healthy Wistar rats were divided into healthy control (n = 15) and
      pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model
      rats were randomly divided into three groups: the model group (n = 15), the sham
      point group (n = 15), and the ST36 group (n = 15). The above three groups
      underwent PET scanning. PET images were processed with SPM2. RESULTS: The brain
      areas that were activated in the sham-point group relative to the model group
      were primarily centred on the bilateral limbic system, the right frontal lobe,
      and the striatum, whereas the activated areas in the ST36 group were primarily
      centred on the bilateral limbic system (pyriform cortex), the bilateral temporal
      lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared
      with the sham-point group, the ST36 group showed greater activation in the
      bilateral amygdalae and the left temporal lobe. CONCLUSION: We concluded that
      needling at a sham point or ST36 can increase blood perfusion and glycol
      metabolism in certain brain areas, and thus may have a positive influence on the
      cognition of AD patients.

PMID- 24886496
TI  - Molecular typing reveals substantial Plasmodium vivax infection in asymptomatic
      adults in a rural area of Cameroon.
AB  - BACKGROUND: Malaria in Cameroon is due to infections by Plasmodium falciparum
      and, to a lesser extent, Plasmodium malariae and Plasmodium ovale, but rarely
      Plasmodium vivax. A recent report suggested "Plasmodium vivax-like" infections
      around the study area that remained unconfirmed. Therefore, molecular and
      antigenic typing was used to investigate the prevalence of P. vivax and Duffy in
      asymptomatic adults resident in Bolifamba. METHODS: A cross-sectional study was
      conducted from July 2008 to October 2009. The status of all parasite species was
      determined by nested PCR in 269 blood samples collected. The P. falciparum and P.
      vivax anti-MSP/CSP antibody status of each subject was also determined
      qualitatively by a rapid card assay. Parasite DNA was extracted from a sample
      infected with three parasite species, purified and sequenced. The Duffy antigen
      status of 12 subjects infected with P. vivax was also determined by sequencing.
      In silico web-based tools were used to analyse sequence data for similarities and
      matches to reference sequences in public DNA databases. RESULTS: The overall
      malaria parasite prevalence in 269 individuals was 32.3% (87) as determined by
      PCR. Remarkably, 14.9% (13/87) of infections were caused either exclusively or
      concomitantly by P. vivax, established both by PCR and microscopic examination of
      blood smears, in individuals both positive (50%, 6/12) and negative (50%, 6/12)
      for the Duffy receptor. A triple infection by P. falciparum, P. vivax and P.
      malariae, was detected in one infected individual. Anti-MSP/CSP antibodies were
      detected in 72.1% (194/269) of samples, indicating high and continuous exposure
      to infection through mosquito bites. DISCUSSION: These data provide the first
      molecular evidence of P. vivax in Duffy positive and negative Cameroonians and
      suggest that there may be a significant prevalence of P. vivax infection than
      expected in the study area. Whether the P. vivax cases were imported or due to
      expansion of a founder effect was not investigated. Notwithstanding, the presence
      of P. vivax may complicate control efforts if these parasites become hypnozoitic
      or latent as the liver stage. CONCLUSIONS: These data strongly suggest that P.
      vivax is endemic to the south-west region of Cameroon and should be taken into
      account when designing malaria control strategies.

PMID- 24886497
TI  - Tick-borne pathogens and associated co-infections in ticks collected from
      domestic animals in central China.
AB  - BACKGROUND: Ticks can transmit a number of pathogens to humans and domestic
      animals. Tick borne diseases (TBDs), which may lead to organ failure and death
      have been recently reported in China. 98.75% of the total cases (>1000) in Henan
      provinces have been reported in Xinyang city. Therefore, the aims of this study
      were to investigate the fauna of ticks and detect the potential pathogens in
      ticks in Xinyang, the region of central China. METHODS: Ticks were collected from
      10 villages of Xinyang from April to December 2012, from domestic animals
      including sheep, cattle and dogs. Then identification of ticks and detection of
      tick-borne pathogens, including Babesia spp., Theileria spp., Anaplasma spp.,
      Ehrlichia spp., Rickettsia spp., tick-borne encephalitis virus (TBEV), Borrelia
      burgdorferi sensu lato, Leishmania infantum, were undertaken by using polymerase
      chain reaction assay (PCR) and sequence analysis. Moreover, the co-infection
      patterns of various pathogens were compared among locations where ticks were
      collected. RESULTS: A total of 308 ticks were collected. Two species of Ixodidae
      were found, namely Haemaphysalis longicornis (96.75%) and Rhipicephalus microplus
      (3.25%). Five genera of pathogens, namely Theileria spp. (3.25%), Anaplasma spp.
      (2.92%), Babesia spp. (1.95%), Ehrlichia spp. (2.92%) and Rickettsia spp.
      (0.65%), were detected in 7 villages. Co-infections by two pathogens were
      diagnosed in 11.11% of all infected ticks. CONCLUSIONS: Both human and animal
      pathogens were abundant in ticks in the study areas. Humans and animals in these
      regions were at a high risk of exposure to piroplasmosis, since piroplasm had the
      highest rates of infection and co-infection in positive ticks.

PMID- 24886499
TI  - Good performances but short lasting efficacy of Actellic 50 EC Indoor Residual
      Spraying (IRS) on malaria transmission in Benin, West Africa.
AB  - BACKGROUND: The National Malaria Control Program (NMCP) has been using pirimiphos
      methyl for the first time for indoor residual spraying (IRS) in Benin. The first
      round was a success with a significant decrease of entomological indicators of
      malaria transmission in the treated districts. We present the results of the
      entomological impact on malaria transmission. Entomologic parameters in the
      control area were compared with those in intervention sites. METHODS: Mosquito
      collections were carried out in three districts in the Atacora-Dongo region of
      which two were treated with pirimiphos methyl (Actellic 50EC) (Tanguieta and
      Kouande) and the untreated (Copargo) served as control. Anopheles gambiae s.l.
      populations were sampled monthly by human landing catch. In addition, window exit
      traps and pyrethrum spray catches were performed to assess exophagic behavior of
      Anopheles vectors. In the three districts, mosquito collections were organized to
      follow the impact of pirimiphos methyl IRS on malaria transmission and possible
      changes in the behavior of mosquitoes. The residual activity of pirimiphos methyl
      in the treated walls was also assessed using WHO bioassay test. RESULTS: A
      significant reduction (94.25%) in human biting rate was recorded in treated
      districts where an inhabitant received less than 1 bite of An. gambiae per night.
      During this same time, the entomological inoculation rate (EIR) dramatically
      declined in the treated area (99.24% reduction). We also noted a significant
      reduction in longevity of the vectors and an increase in exophily induced by
      pirimiphos methyl on An. gambiae. However, no significant impact was found on the
      blood feeding rate. Otherwise, the low residual activity of Actellic 50 EC, which
      is three months, is a disadvantage. CONCLUSION: Pirimiphos methyl was found to be
      effective for IRS in Benin. However, because of the low persistence of Actellic
      50EC used in this study on the treated walls, the recourse to another more
      residual formulation of pirimiphos methyl is required.

PMID- 24886498
TI  - Cohort profile: Greifswald approach to individualized medicine (GANI_MED).
AB  - BACKGROUND: Individualized Medicine aims at providing optimal treatment for an
      individual patient at a given time based on his specific genetic and molecular
      characteristics. This requires excellent clinical stratification of patients as
      well as the availability of genomic data and biomarkers as prerequisites for the
      development of novel diagnostic tools and therapeutic strategies. The University
      Medicine Greifswald, Germany, has launched the "Greifswald Approach to
      Individualized Medicine" (GANI_MED) project to address major challenges of
      Individualized Medicine. Herein, we describe the implementation of the scientific
      and clinical infrastructure that allows future translation of findings relevant
      to Individualized Medicine into clinical practice. METHODS/DESIGN: Clinical
      patient cohorts (N > 5,000) with an emphasis on metabolic and cardiovascular
      diseases are being established following a standardized protocol for the
      assessment of medical history, laboratory biomarkers, and the collection of
      various biosamples for bio-banking purposes. A multi-omics based biomarker
      assessment including genome-wide genotyping, transcriptome, metabolome, and
      proteome analyses complements the multi-level approach of GANI_MED. Comparisons
      with the general background population as characterized by our Study of Health in
      Pomerania (SHIP) are performed. A central data management structure has been
      implemented to capture and integrate all relevant clinical data for research
      purposes. Ethical research projects on informed consent procedures, reporting of
      incidental findings, and economic evaluations were launched in parallel.

PMID- 24886500
TI  - G1 checkpoint establishment in vivo during embryonic liver development.
AB  - BACKGROUND: The DNA damage-mediated cell cycle checkpoint is an essential
      mechanism in the DNA damage response (DDR). During embryonic development, the
      characteristics of cell cycle and DNA damage checkpoint evolve from an extremely
      short G1 cell phase and lacking G1 checkpoint to lengthening G1 phase and the
      establishment of the G1 checkpoint. However, the regulatory mechanisms governing
      these transitions are not well understood. In this study, pregnant mice were
      exposed to ionizing radiation (IR) to induce DNA damage at different embryonic
      stages; the kinetics and mechanisms of the establishment of DNA damage-mediated
      G1 checkpoint in embryonic liver were investigated. RESULTS: We found that the G2
      cell cycle arrest was the first response to DNA damage in early developmental
      stages. Starting at E13.5/E15.5, IR mediated inhibition of the G1 to S phase
      transition became evident. Concomitantly, IR induced the robust expression of p21
      and suppressed Cdk2/cyclin E activity, which might involve in the initiation of
      G1 checkpoint. The established G1 cell cycle checkpoint, in combination with an
      enhanced DNA repair capacity at E15.5, displayed biologically protective effects
      of repairing DNA double-strand breaks (DSBs) and reducing apoptosis in the short
      term as well as reducing chromosome deletion and breakage in the long term.
      CONCLUSION: Our study is the first to demonstrate the establishment of the DNA
      damage-mediated G1 cell cycle checkpoint in liver cells during embryogenesis and
      its in vivo biological effects during embryonic liver development.

PMID- 24886501
TI  - Flux analysis of the Lactobacillus reuteri propanediol-utilization pathway for
      production of 3-hydroxypropionaldehyde, 3-hydroxypropionic acid and 1,3
      propanediol from glycerol.
AB  - BACKGROUND: Lactobacillus reuteri converts glycerol to 3-hydroxypropionic acid
      (3HP) and 1,3-propanediol (1,3PDO) via 3-hydroxypropionaldehyde (3HPA) as an
      intermediate using enzymes encoded in its propanediol-utilization (pdu) operon.
      Since 3HP, 1,3PDO and 3HPA are important building blocks for the bio-based
      chemical industry, L. reuteri can be an attractive candidate for their
      production. However, little is known about the kinetics of glycerol utilization
      in the Pdu pathway in L. reuteri. In this study, the metabolic fluxes through the
      Pdu pathway were determined as a first step towards optimizing the production of
      3HPA, and co-production of 3HP and 1,3PDO from glycerol. Resting cells of wild
      type (DSM 20016) and recombinant (RPRB3007, with overexpressed pdu operon)
      strains were used as biocatalysts. RESULTS: The conversion rate of glycerol to
      3HPA by the resting cells of L. reuteri was evaluated by in situ complexation of
      the aldehyde with carbohydrazide to avoid the aldehyde-mediated inactivation of
      glycerol dehydratase. Under operational conditions, the specific 3HPA production
      rate of the RPRB3007 strain was 1.9 times higher than that of the wild-type
      strain (1718.2 versus 889.0 mg/gCDW.h, respectively). Flux analysis of glycerol
      conversion to 1,3PDO and 3HP in the cells using multi-step variable-volume fed
      batch operation showed that the maximum specific production rates of 3HP and
      1,3PDO were 110.8 and 93.7 mg/gCDW.h, respectively, for the wild-type strain, and
      179.2 and 151.4 mg/gCDW.h, respectively, for the RPRB3007 strain. The cumulative
      molar yield of the two compounds was ~1 mol/mol glycerol and their molar ratio
      was ~1 mol3HP/mol1,3PDO. A balance of redox equivalents between the glycerol
      oxidative and reductive pathway branches led to equimolar amounts of the two
      products. CONCLUSIONS: Metabolic flux analysis was a useful approach for finding
      conditions for maximal conversion of glycerol to 3HPA, 3HP and 1,3PDO. Improved
      specific production rates were obtained with resting cells of the engineered
      RPRB3007 strain, highlighting the potential of metabolic engineering to render an
      industrially sound strain. This is the first report on the production of 3HP and
      1,3PDO as sole products using the wild-type or mutant L. reuteri strains, and has
      laid ground for further work on improving the productivity of the
      biotransformation process using resting cells.

PMID- 24886502
TI  - Intestinal parasitoses in a tertiary-care hospital located in a non-endemic
      setting during 2006-2010.
AB  - BACKGROUND: The aim of this study was to assess the epidemiology of intestinal
      parasitoses during a 5-year period in patients attending a tertiary-care hospital
      in a non-endemic setting. METHODS: In the period 2006-2010, 15,752 samples from
      8,886 patients with clinically suspected parasitosis were subjected to
      macroscopic and microscopic examination, to parasitic antigen detection assays,
      and to cultures for protozoa and nematodes. Real-time PCR assays for the
      differentiation of Entamoeba histolytica and E. dispar and for the detection of
      Dientamoeba fragilis were also used.A statistical analysis evaluating the
      demographic data of the patients with intestinal parasitic infections was
      performed. RESULTS: Intestinal parasitic infections were diagnosed in 1,477
      patients (16.6% prevalence), mainly adults and immigrants from endemic areas for
      faecal-oral infections; protozoa were detected in 93.4% and helminths in 6.6% of
      the cases, the latter especially in immigrants. Blastocystis hominis was the most
      common intestinal protozoan, and G. intestinalis was the most frequently detected
      among pathogenic protozoa, prevalent in immigrants, males, and pediatric
      patients. Both single (77.9%) and mixed (22.1%) parasitic infections were
      observed, the latter prevalent in immigrants. CONCLUSIONS: Despite the importance
      of the knowledge about the epidemiology of intestinal parasitoses in order to
      adopt appropriate control measures and adequate patient care all over the world,
      data regarding industrialized countries are rarely reported in the literature.
      The data presented in this study indicate that intestinal parasitic infections
      are frequently diagnosed in our laboratory and could make a contribution to
      stimulate the attention by physicians working in non-endemic areas on the
      importance of suspecting intestinal parasitoses.

PMID- 24886503
TI  - Astroglial-axonal interactions during early stages of myelination in mixed
      cultures using in vitro and ex vivo imaging techniques.
AB  - BACKGROUND: [corrected] Myelination is a very complex process that requires the
      cross talk between various neural cell types. Previously, using cytosolic or
      membrane associated GFP tagged neurospheres, we followed the interaction of
      oligodendrocytes with axons using time-lapse imaging in vitro and ex vivo and
      demonstrated dynamic changes in cell morphology. In this study we focus on GFP
      tagged astrocytes differentiated from neurospheres and their interactions with
      axons. RESULTS: We show the close interaction of astrocyte processes with axons
      and with oligodendrocytes in mixed mouse spinal cord cultures with formation of
      membrane blebs as previously seen for oligodendrocytes in the same cultures. When
      GFP-tagged neurospheres were transplanted into the spinal cord of the
      dysmyelinated shiverer mouse, confirmation of dynamic changes in cell morphology
      was provided and a prevalence for astrocyte differentiation compared with
      oligodendroglial differentiation around the injection site. Furthermore, we were
      able to image GFP tagged neural cells in vivo after transplantation and the cells
      exhibited similar membrane changes as cells visualised in vitro and ex vivo.
      CONCLUSION: These data show that astrocytes exhibit dynamic cell process movement
      and changes in their membrane topography as they interact with axons and
      oligodendrocytes during the process of myelination, with the first demonstration
      of bleb formation in astrocytes.

PMID- 24886504
TI  - Association between osteoporosis and benign paroxysmal positional vertigo: a
      systematic review.
AB  - BACKGROUND: Increasing recent evidence has implicated osteoporosis as a risk
      factor for benign paroxysmal positional vertigo (BPPV). We conducted a systematic
      review to examine the association between osteoporosis and BPPV. METHODS: Four
      electronic databases (PubMed, EMBASE, Cochrane Library, and the China Network
      Knowledge Infrastructure) were searched to identify all papers, published in
      either English or Chinese, examining the association between osteoporosis
      (osteopenia) and BPPV. RESULTS: Seven studies were eligible for analysis, though
      these studies included some weaknesses. Most of the studies demonstrated a
      correlation between osteoporosis (osteopenia) and the occurrence and recurrence
      of BPPV, especially in older women. Patients with osteoporosis may require more
      canalith-repositioning procedures. CONCLUSIONS: This systematic review provides
      insight into currently available evidence and elucidates the possible existence
      of an association between BPPV and osteoporosis (osteopenia). However, the
      evidence supporting that conclusion is not strong, and further studies are needed
      to clarify the association between these conditions.

PMID- 24886505
TI  - Quick biochemical markers for assessment of quality control of intraoperative
      cell salvage: a prospective observational study.
AB  - BACKGROUND: Intraoperative Cell Salvage (ICS), hereby referred to 'mechanical red
      cell salvage', has been widely used in adult elective major surgeries to reduce
      requirement for homologous red blood cell transfusion and its associated
      complications. However, amount of free haemoglobin (fHb) from ICS has been shown
      related to incidence of renal failure. fHb is the most important indicator of
      quality control of cell salvaged blood, thus monitoring the fHb concentration is
      imperative to minimise renal injury. However, currently there has been lacking
      quick biochemical markers to monitor the levels of fHb during ICS. The aim of
      this study was to screen quick biochemical markers for evaluating the amount of
      fHb during use of intraoperative cell salvage. METHODS: Twenty patients
      undergoing elective cardiovascular surgery were enrolled. Blood was collected and
      processed using a Fresenius continuous auto-transfusion system device. The
      concentration of fHb, albumin (Alb), and calcium (Ca) in three washing modes were
      measured, and their clearance rates were calculated. The correlations among the
      clearances and concentrations of fHb, albumin, and calcium were analysed.
      RESULTS: In three washing modes, concentrations of albumin and calcium are
      significantly associated with amount of fHb:fHb(g/L) = 0.111 Alb(g/L) -0.108, R =
      0.638, p = 0.000; fHb(g/L) = 1.721 Ca(mmol/L) +0.091, R = 0.514, p = 0.000.
      Furthermore, the clearance rates of albumin and calcium significantly predict
      clearance of fHb, CR(fHb) = 0.310 CR(ALB) + 0.686, R = 0.753, p = 0.000, CR(fHb)
      = 0.073 CR(Ca) + 0.913, R = 0.497, p = 0.000. CONCLUSIONS: In clinic practice,
      clearance rates of albumin, or calcium can be used to evaluate the quality of
      salvaged blood, fHb. Bed-side measurement of calcium could offer a more feasible
      means for clinicians to undertake a real-time assessment of fHb.

PMID- 24886506
TI  - Evaluation of existence and transmission of extended spectrum beta lactamase
      producing bacteria from post-delivery women to neonates at Bugando Medical
      Center, Mwanza-Tanzania.
AB  - BACKGROUND: Extended spectrum beta-lactamase producing bacteria (ESBL) are common
      causes of neonatal sepsis worldwide. Neonatal sepsis due to ESBL is associated
      with increased morbidity and mortality at Bugando Medical Centre (BMC). Due to
      limited information on the sources of these ESBL strains at BMC, this study was
      conducted to evaluate the existence, magnitude and transmission of ESBL from post
      delivery women to neonates at BMC, Mwanza-Tanzania. RESULTS: A cross-sectional
      study was conducted at obstetrics and neonatal wards from May to July 2013,
      involving post-delivery women and their neonates. Rectal swabs were collected and
      processed to identify the ESBL strains and their antimicrobial susceptibility
      patterns. Patients' data were obtained using a standardized data collection tool.
      We enrolled 113 women and 126 neonates with mean age of 26.5 +/- 5.5 years and
      median gestation age [IQR] of 39 [35-40] weeks respectively. The prevalence of
      ESBL carriage among women and neonates were 15% (17/113) and 25.4% (32/126)
      respectively. The acquisition of ESBL isolates among neonates on day 1, day 3 and
      day 7 were 60.0% (21/35), 25.7% (9/35) and 14.3% (5/35) respectively. There was
      no phenotypic similarity between ESBL strains from women and their respective
      neonates, suggesting other sources of transmission. Neonates given antibiotics
      were more likely to carry ESBL than those not given [100% (32/32) versus 86%
      (81/94), p = 0.018]. CONCLUSION: The carriage rate of ESBL strains among post
      delivery women and neonates at BMC is high. Our findings suggest that neonates
      acquire these strains from sources other than post-delivery women and more than
      half acquire them on the first day of life. More studies are recommended to
      further explore the sources of ESBL strains among neonates.

PMID- 24886507
TI  - Quality of life and health care consumption in primary care patients with
      elevated serum calcium concentrations in - a prospective, case control, study.
AB  - BACKGROUND: Patients with elevated calcium concentrations have an increased
      morbidity due to various underlying illnesses. However, there is a lack of
      studies of quality of life and health care consumption in patients with
      hypercalcaemia per se. The study aims to investigate quality of life and health
      care consumption, as measured by, sick leave, drug prescriptions and the number
      of visits and admissions to health care centres and hospitals, in primary care
      patients with elevated calcium concentrations. METHODS: A prospective, case
      control, study in primary care centre, in Sweden. Patients with elevated, (n=127,
      28 men), and normal calcium concentrations, (n=254, 56 men), mean age 61.4 year,
      were recruited in the study and followed during 10 years. Eighty-six percent of
      those alive at the time of follow up participated in a follow up visit. The study
      participants completed a quality of life survey, SF-36, which also were compared
      with the Swedish SF-36 national normative database. RESULTS: Patients with
      elevated calcium concentrations had significantly lower quality of life both
      compared with the control group (patients with normal calcium concentrations) and
      compared with age and gender-matched reference material from the Swedish SF-36
      national normative database. The group with elevated calcium concentrations had
      significantly more hospitalisations (p=0.017), subsequently cancer diagnoses
      (p<0.003), sick leave (p=0.007) and medication (p=0.002) compared with patients
      with normal calcium concentrations. Men with elevated calcium concentrations had
      more contacts with the psychosocial team (p=0.02) at the health care centre.
      CONCLUSIONS: Elevated calcium concentrations are associated with significantly
      reduced quality of life and increased health care consumption and should
      therefore be an important warning flag that should alert the physician to further
      investigate and care for the patient. This is the first study in this field and
      the results need to be confirmed in further studies.

PMID- 24886508
TI  - Acid mediates a prolonged antinociception via substance P signaling in acid
      induced chronic widespread pain.
AB  - BACKGROUND: Substance P is an important neuropeptide released from nociceptors to
      mediate pain signals. We recently revealed antinociceptive signaling by substance
      P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse
      model of acid-induced chronic widespread pain. However, methods to specifically
      trigger the substance P antinociception were still lacking. RESULTS: Here we show
      that acid could induce antinociceptive signaling via substance P release in
      muscle. We prevented the intramuscular acid-induced hyperalgesia by
      pharmacological inhibition of ASIC3 and transient receptor potential V1 (TRPV1).
      The antinociceptive effect of non-ASIC3, non-TRPV1 acid signaling lasted for 2
      days. The non-ASIC3, non-TRPV1 acid antinociception was largely abolished in mice
      lacking substance P. Moreover, pretreatment with substance P in muscle mimicked
      the acid antinociceptive effect and prevented the hyperalgesia induced by next
      day acid injection. CONCLUSIONS: Acid could mediate a prolonged antinociceptive
      signaling via the release of substance P from muscle afferent neurons in a non
      ASIC3, non-TRPV1 manner.

PMID- 24886509
TI  - Immunohistochemical assessment of a unique basal pattern of p53 expression in
      ulcerative-colitis-associated neoplasia using computer-assisted cytometry.
AB  - BACKGROUND: The basal pattern of p53 expression, defined as its immunoreactivity
      confined to the basal half of the glands, is associated with early neoplastic
      lesions in ulcerative colitis (UC). However, their clinical utility of this
      finding is limited by the use of "visual estimation" (approximate
      immunoreactivity on the basis of scanning the stained slide, without formal
      counting). This study was designed to analyze the basal pattern of p53 using
      computer-assisted cytometry and to identify the optimal cutoff value for
      discriminating between UC-associated early-stage neoplasia and regenerative
      atypia. METHODS: The specimens were obtained from eight UC patients undergoing
      colectomy and were classified according to the criteria by the Research Committee
      of Inflammatory Bowel Disease of the Ministry of Health and Welfare in Japan.
      Patients with classes UC-IIa (indefinite for dysplasia, probably regenerative),
      UC-IIb (indefinite for dysplasia, probably dysplastic), and UC-III (definitive
      dysplasia) were enrolled in the study. Based on the percentage of immunoreactive
      cells in the basal half of the crypt with visual estimation, basal positivity of
      p53 was classified into three categories: grade 1 (1 - 9%), grade 2 (10 - 19%),
      and grade 3 (>= 20%). Next, crypts classified as grade 3 by visual estimation
      were analyzed by computer-assisted image analysis. RESULTS: Using visual
      estimation, grade-3 p53 basal positivity was observed in 46.0% of UC-IIa crypts
      (128 of 278), 61.9% of UC-IIb crypts (39 of 63), and 94.2% of UC-III crypts (81
      of 86). Using image analysis, the median p53 basal positivities were 30.3% in UC
      IIa, 52.3% in UC-IIb, and 65.4% in UC-III (P <= 0.002). A receiver operating
      characteristics curve was generated to determine the method's diagnostic utility
      in differentiating UC-IIa from UC-III. In this cohort, the sensitivity was 0.78;
      the specificity was 0.98; the negative predictive value was 87.4%; the positive
      predictive value was 95.5%, and the accuracy was 90.2% with a cutoff value for
      p53 basal positivity of 46.1%. CONCLUSIONS: Our findings indicate that assessing
      p53 basal positivity by image analysis with an optimal threshold represents an
      alternative to visual estimation for the accurate diagnosis of UC-associated
      early-stage neoplasia. VIRTUAL SLIDES: The virtual slide(s) for this article can
      be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3588120501252608.

PMID- 24886510
TI  - A recently introduced Dichelobacter nodosus strain caused an outbreak of footrot
      in Norway.
AB  - BACKGROUND: In 2008, an outbreak of ovine footrot occurred in Norway.
      Dichelobacter nodosus isolates collected between 2008 and 2011 have been
      characterised. Isolates defined as virulent by the gelatin gel test (GG-test)
      were only found in sheep in Rogaland County, where the severe cases of footrot
      were registered. The majority (96%) of the virulent isolates belonged to
      serogroup A. It is suspected that they represent a newly introduced strain, and
      the aim of the present study was to investigate whether they are genetically
      similar. Sixty-one virulent isolates from sheep and 116 benign isolates from
      sheep, cattle and goats were included. Four GG-test virulent isolates from Danish
      sheep were also included. All isolates were genotyped by pulsed-field gel
      electrophoresis (PFGE) and by PCR for pgr variant determination. RESULTS: The
      Norwegian virulent isolates were assigned to 8 pulsotypes (PTs), while the benign
      isolates were assigned to 66 PTs. Thirty-seven (68.5%) of the 54, virulent,
      serogroup A isolates belonged to the same PT, and included isolates from 2008
      through 2011. Isolates belonging to this PT were defined as the outbreak strain.
      The remaining virulent serogroup A isolates belonged to 4 PTs differing by <=3
      bands from the outbreak strain. Two virulent, Danish, serogroup A isolates
      differed by 2 bands from the Norwegian outbreak strain. All but 3 (95%) of the
      virulent isolates had the pgrA variant while 85% of the benign isolates had the
      pgrB variant. CONCLUSION: This study provides evidence that the footrot outbreak
      in Norway in 2008 most likely was caused by new introduction and local spread of
      one virulent D. nodosus strain.

PMID- 24886511
TI  - Generation of orientation tools for automated zebrafish screening assays using
      desktop 3D printing.
AB  - BACKGROUND: The zebrafish has been established as the main vertebrate model
      system for whole organism screening applications. However, the lack of consistent
      positioning of zebrafish embryos within wells of microtiter plates remains an
      obstacle for the comparative analysis of images acquired in automated screening
      assays. While technical solutions to the orientation problem exist, dissemination
      is often hindered by the lack of simple and inexpensive ways of distributing and
      duplicating tools. RESULTS: Here, we provide a cost effective method for the
      production of 96-well plate compatible zebrafish orientation tools using a
      desktop 3D printer. The printed tools enable the positioning and orientation of
      zebrafish embryos within cavities formed in agarose. Their applicability is
      demonstrated by acquiring lateral and dorsal views of zebrafish embryos arrayed
      within microtiter plates using an automated screening microscope. This enables
      the consistent visualization of morphological phenotypes and reporter gene
      expression patterns. CONCLUSIONS: The designs are refined versions of previously
      demonstrated devices with added functionality and strongly reduced production
      costs. All corresponding 3D models are freely available and digital design can be
      easily shared electronically. In combination with the increasingly widespread
      usage of 3D printers, this provides access to the developed tools to a wide range
      of zebrafish users. Finally, the design files can serve as templates for other
      additive and subtractive fabrication methods.

PMID- 24886512
TI  - Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients
      with metastatic renal cell carcinoma.
AB  - BACKGROUND: The incidence of renal cell cancer (RCC) has been increasing for the
      past decade, and the 5-year survival for patients with metastatic RCC (mRCC) is
      rather low. Everolimus (RAD001), a new inhibitor for mammalian target of
      rapamycin (mTOR), is generally well tolerated, and demonstrates clinical benefit
      to patients with anti-VEGF-refractory mRCC. However, factors for selection of
      patients who may benefit from everolimus remain largely unknown. Here we aimed to
      explore potential molecular indicators for mRCC patients who may benefit from
      everolimus treatment. METHODS: Paraffin-embedded tumor tissue specimens derived
      from 18 mRCC patients before everolimus treatment, who participated the phase 1b
      trial of everolimus in VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI)
      refractory Chinese patients with mRCC (clinicaltrials.gov, NCT01152801), were
      examined for the expression levels of phosphorylated AKT, mTOR, eukaryotic
      initiation factor 4E (eIF4E) binding protein-1 (4EBP1) and 40S ribosomal protein
      S6 (S6RP) by immunohistochemistry. Clinical benefit rate (complete response [CR],
      partial response [PR], plus stable disease [SD] >= 6 months) and progression-free
      survival time (PFS) were correlated with expression levels of these mTOR
      associated molecules. RESULTS: In these 18 patients, there were 1 PR, 15 SDs
      (including 9 SDs >= 6 months), and 2 progressive diseases (PD). The clinical
      benefit rate (CBR) was 55.6% (10/18), and the median PFS time was 8.4 months.
      Patients with positive expression of phospho-mTOR showed a better CBR (71.4%
      versus 0%, P = 0.023) and PFS time (11.3 versus 3.7 months, P = 0.001) than those
      patients with negative expression. The median PFS of patients with positive
      phospho-S6RP expression was longer (11.3 versus 3.7 months, P = 0.002) than that
      of patients negative for phospho-S6RP expression. However, expression levels of
      phospho-4EBP1 and phospho-AKT were unassociated to efficacy of everolimus
      treatment with respect to CBR and PFS. Co-expression of phosphorylated mTOR, S6RP
      and/or 4EBP1 may improve the predictive value of the biomarkers for patients
      treated with everolimus. CONCLUSIONS: The expression levels of phospho-mTOR and
      phospho-S6RP may be potential predictive biomarkers for efficacy of everolimus in
      patients with mRCC. Combining examinations of phosphorylated mTOR, S6RP and/or
      4EBP1 may be a potential strategy to select mRCC patients sensitive to mTOR
      inhibitor treatment.

PMID- 24886514
TI  - Establishment of a pancreatic stem cell line from fibroblast-derived induced
      pluripotent stem cells.
AB  - BACKGROUND: For cell therapies to treat diabetes, it is important to produce a
      sufficient number of pancreatic endocrine cells that function similarly to
      primary islets. Induced pluripotent stem (iPS) cells represent a potentially
      unlimited source of functional pancreatic endocrine cells. However, the use of
      iPS cells for laboratory studies and cell-based therapies is hampered by their
      high tumorigenic potential and limited ability to generate pure populations of
      differentiated cell types in vitro. The purpose of this study was to establish a
      pancreatic stem cell line from iPS cells derived from mouse fibroblasts. METHODS:
      Mouse iPS cells were induced to differentiate into insulin-producing cells by a
      multi-step differentiation protocol, which was conducted as described previously
      with minor modifications. Selection of the pancreatic stem cell was based on
      morphology and Pdx1 expression. The pancreatic potential of the pancreatic stem
      cells was evaluated using a reverse transcription PCR, real-time PCR,
      immunofluorescence, and a glucose challenge test. To assess potential
      tumorigenicity of the pancreatic stem cells, the cells were injected into the
      quadriceps femoris muscle of the left hindlimb of nude mice. RESULTS: The iPS
      derived pancreatic stem cells expressed the transcription factor--Pdx1--a marker
      of pancreatic development, and continued to divide actively beyond passage 80.
      Endocrine cells derived from these pancreatic stem cells expressed insulin and
      pancreatic genes, and they released insulin in response to glucose stimulation.
      Mice injected with the pancreatic stem cells did not develop tumors, in contrast
      to mice injected with an equal number of iPS cells. CONCLUSION: This strategy
      provides a new approach for generation of insulin-producing cells that is more
      efficient and safer than using iPS cells. We believe that this approach will help
      to develop a patient-specific cell transplantation therapy for diabetes in the
      near future.

PMID- 24886515
TI  - Reporting individual results for biomonitoring and environmental exposures:
      lessons learned from environmental communication case studies.
AB  - Measurement methods for chemicals in biological and personal environmental
      samples have expanded rapidly and become a cornerstone of health studies and
      public health surveillance. These measurements raise questions about whether and
      how to report individual results to study participants, particularly when health
      effects and exposure reduction strategies are uncertain. In an era of greater
      public participation and open disclosure in science, researchers and
      institutional review boards (IRBs) need new guidance on changing norms and best
      practices. Drawing on the experiences of researchers, IRBs, and study
      participants, we discuss ethical frameworks, effective methods, and outcomes in
      studies that have reported personal results for a wide range of environmental
      chemicals. Belmont Report principles and community-based participatory research
      ethics imply responsibilities to report individual results, and several recent
      biomonitoring guidance documents call for individual reports. Meaningful report
      back includes contextual information about health implications and exposure
      reduction strategies. Both narrative and graphs are helpful. Graphs comparing an
      individual's results with other participants in the study and benchmarks, such as
      the National Exposure Report, are helpful, but must be used carefully to avoid
      incorrect inferences that higher results are necessarily harmful or lower results
      are safe. Methods can be tailored for specific settings by involving participants
      and community members in planning. Participants and researchers who have
      participated in report-back identified benefits: increasing trust in science,
      retention in cohort studies, environmental health literacy, individual and
      community empowerment, and motivation to reduce exposures. Researchers as well as
      participants gained unexpected insights into the characteristics and sources of
      environmental contamination. Participants are almost universally eager to receive
      their results and do not regret getting them. Ethical considerations and
      empirical experience both support study participants' right to know their own
      results if they choose, so report-back should become the norm in studies that
      measure personal exposures. Recent studies provide models that are compiled in a
      handbook to help research partnerships that are planning report-back. Thoughtful
      report-back can strengthen research experiences for investigators and
      participants and expand the translation of environmental health research in
      communities. 

PMID- 24886513
TI  - Synovial explant inflammatory mediator production corresponds to rheumatoid
      arthritis imaging hallmarks: a cross-sectional study.
AB  - INTRODUCTION: Despite the widespread use of magnetic resonance imaging (MRI) and
      Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease
      activity, little is known regarding the association of imaging-detected activity
      and synovial pathology. The purpose of this study was to compare site-specific
      release of inflammatory mediators and evaluate the corresponding anatomical sites
      by examining colour Doppler ultrasound (CDUS) and MRI scans. METHODS: RA patients
      were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent
      synovectomy using a needle arthroscopic procedure of the hand joints. The
      synovial tissue specimens were incubated for 72 hours, and spontaneous release of
      monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage
      inflammatory protein 1beta (MIP-1beta) and IL-8 was measured by performing
      multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores
      were estimated on the basis of the rheumatoid arthritis magnetic resonance
      imaging score (RAMRIS). Mixed models were used for the statistical analyses.
      Parsimony was achieved by omitting covariates with P > 0.1 from the statistical
      model. RESULTS: Tissue samples from 58 synovial sites were obtained from 25
      patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate
      Spearman's rho = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman's rho =
      0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman's rho = 0.31). IL
      6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman's
      rho = 0.50), BME score (P = 0.04, approximate Spearman's rho = 0.31) and RAMRIS
      erosion score (P = 0.03, approximate Spearman's rho = 0.35). MIP-1beta was
      associated with CDUS activity (P = 0.02, approximate Spearman's rho = 0.38) and
      RAMRIS synovitis scores (P = 0.02, approximate Spearman's rho = 0.63). IL-8
      associations with imaging outcome measures did not reach statistical
      significance. CONCLUSIONS: The association between imaging activity and synovial
      inflammatory mediators underscores the high sensitivity of CDUS and MRI in the
      evaluation of RA disease activity. The associations found in our present study
      have different implications for synovial mediator releases and corresponding
      imaging signs. For example, MCP-1 and IL-6 were associated with both general
      inflammation and bone destruction, in contrast to MIP-1beta, which was involved
      solely in general synovitis. The lack of association of IL-8 with synovitis was
      likely underestimated because of a large proportion of samples above assay
      detection limits among the patients with the highest synovitis scores.

PMID- 24886516
TI  - Randomised controlled feasibility trial of a web-based weight management
      intervention with nurse support for obese patients in primary care.
AB  - BACKGROUND: There is a need for cost-effective weight management interventions
      that primary care can deliver to reduce the morbidity caused by obesity.
      Automated web-based interventions might provide a solution, but evidence suggests
      that they may be ineffective without additional human support. The main aim of
      this study was to carry out a feasibility trial of a web-based weight management
      intervention in primary care, comparing different levels of nurse support, to
      determine the optimal combination of web-based and personal support to be tested
      in a full trial. METHODS: This was an individually randomised four arm parallel
      non-blinded trial, recruiting obese patients in primary care. Following online
      registration, patients were randomly allocated by the automated intervention to
      either usual care, the web-based intervention only, or the web-based intervention
      with either basic nurse support (3 sessions in 3 months) or regular nurse support
      (7 sessions in 6 months). The main outcome measure (intended as the primary
      outcome for the main trial) was weight loss in kg at 12 months. As this was a
      feasibility trial no statistical analyses were carried out, but we present means,
      confidence intervals and effect sizes for weight loss in each group, uptake and
      retention, and completion of intervention components and outcome measures.
      RESULTS: All randomised patients were included in the weight loss analyses (using
      Last Observation Carried Forward). At 12 months mean weight loss was: usual care
      group (n = 43) 2.44 kg; web-based only group (n = 45) 2.30 kg; basic nurse
      support group (n = 44) 4.31 kg; regular nurse support group (n = 47) 2.50 kg.
      Intervention effect sizes compared with usual care were: d = 0.01 web-based; d =
      0.34 basic nurse support; d = 0.02 regular nurse support. Two practices deviated
      from protocol by providing considerable weight management support to their usual
      care patients. CONCLUSIONS: This study demonstrated the feasibility of delivering
      a web-based weight management intervention supported by practice nurses in
      primary care, and suggests that the combination of the web-based intervention
      with basic nurse support could provide an effective solution to weight management
      support in a primary care context. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN31685626.

PMID- 24886517
TI  - Determinants of neonatal mortality in Nigeria: evidence from the 2008 demographic
      and health survey.
AB  - BACKGROUND: Nigeria continues to have one of the highest rates of neonatal deaths
      in Africa. This study aimed to identify risk factors associated with neonatal
      death in Nigeria using the 2008 Nigeria Demographic and Health Survey (NDHS).
      METHODS: Neonatal deaths of all singleton live-born infants between 2003 and 2008
      were extracted from the 2008 NDHS. The 2008 NDHS was a multi-stage cluster sample
      survey of 36,298 households. Of these households, survival information of 27,147
      singleton live-borns was obtained, including 996 cases of neonatal mortality. The
      risk of death was adjusted for confounders relating to individual, household, and
      community level factors using Cox regression. RESULTS: Multivariable analyses
      indicated that a higher birth order of newborns with a short birth interval <= 2
      years (hazard ratio [HR] = 2.19, confidence interval [CI]: 1.68-2.84) and
      newborns with a higher birth order with a longer birth interval > 2 years (HR =
      1.36, CI: 1.05-1.78) were significantly associated with neonatal mortality. Other
      significant factors that affected neonatal deaths included neonates born to
      mothers younger than 20 years (HR = 4.07, CI: 2.83-5.86), neonates born to
      mothers residing in rural areas compared with urban residents (HR = 1.26, CI:
      1.03-1.55), male neonates (HR = 1.30, CI: 1.12-1.53), mothers who perceived their
      neonate's body size to be smaller than the average size (HR = 2.10, CI: 1.77
      2.50), and mothers who delivered their neonates by caesarean section (HR = 2.80,
      CI: 1.84-4.25). CONCLUSIONS: Our study suggests that the Nigerian government
      needs to invest more in the healthcare system to ensure quality care for women
      and newborns. Community-based intervention is also required and should focus on
      child spacing, childbearing at a younger age, and poverty eradication programs,
      particularly in rural areas, to reduce avoidable neonatal deaths in Nigeria.

PMID- 24886518
TI  - Suicide and suicide attempts in people with severe mental disorders in Butajira,
      Ethiopia: 10 year follow-up of a population-based cohort.
AB  - BACKGROUND: People with severe mental disorders (SMD) are at higher risk of
      suicide. However, research into suicide attempts and completed suicide in people
      with SMD in low- and middle-income countries is mostly limited to patients
      attending psychiatric facilities where selection bias is likely to be high.
      METHODS: A population-based cohort of 919 people with SMD from rural Ethiopia
      (who received standardized clinician diagnoses of schizophrenia (n = 358) major
      depressive disorder (n = 216) and bipolar I disorder (n = 345)) were followed up
      annually for an average of 10 years. The Longitudinal Interval Follow-up
      Evaluation chart was administered by psychiatrists and used to evaluate
      systematically suicidal behavior and risk factors, which may be amenable to
      intervention. RESULTS: Over the follow-up period, the cumulative risk of suicide
      attempt was 26.3% for major depression, 23.8% for bipolar I disorder and 13.1%
      for schizophrenia, (p < 0.001). The overall incidence of completed suicide was
      200.2/100,000 person-years (CI = 120.6, 312.5). Hanging was the most frequent
      method used (71.5%) for both attempters and completers. Most people who completed
      suicide were successful on the first attempt (84.2%), but the case-fatality rate
      for suicide attempt was 9.7%. In the adjusted logistic regression model, being
      currently married (Adjusted OR) =2.17, 95% CI = 1.21, 3.91), and having a
      diagnosis of bipolar I disorder (Adjusted OR = 2.59, 95% CI = 1.57, 4.26) or
      major depression (Adjusted OR = 2.71, 95% CI = 1.60, 4.58) were associated
      significantly with increased risk of suicide attempts. CONCLUSION: In this sample
      of people with SMD from a rural setting, the rate of suicide was high.
      Initiatives to integrate mental health service into primary care need to focus on
      limiting access to suicide methods in people with SMD in addition to expanding
      access to mental health care.

PMID- 24886519
TI  - CA15-3 is a useful serum tumor marker for diagnostic integration of hybrid
      positron emission tomography with integrated computed tomography during follow-up
      of breast cancer patients.
AB  - BACKGROUND: The aim of this study was to evaluate the value of CA15-3 for the
      diagnostic integration of molecular imaging findings performed with hybrid
      positron emission tomography and computed tomography (PETCT) technology. METHODS:
      We retrospectively selected 45 patients with a median age of 60 years (range 39
      85 years) and a previous history of breast cancer (BC) who had already been
      treated with surgery and other treatments. Three measurements of CA15-3 were
      collected within 1 year before PETCT examination, at 6-9 months 3-6 months and 0
      3 months before PETCT. The prolonged clinical outcome or imaging follow-up was
      used to define disease relapse. An increase in tumor marker value was compared
      with PETCT findings and disease relapse. Sensitivity and specificity for both
      tests were calculated with respect to clinical outcome. RESULTS: Disease relapse
      was detected in 16 out of 45 BC patients. CA15-3 and PETCT showed 75% sensitivity
      with a specificity percentage of 76% for CA15-3 and 79% for PETCT. Serum CA15-3
      expression levels were significantly higher in BC patients with multiple
      metastatic sites with hepatic involvement. Analysis of serial CA15-3 serum levels
      showed an increase in CA15-3 3-6 months before PETCT could identify BC patients
      at risk for relapse (AUC = 0.81). Moreover, patients receiving anti-hormonal or
      chemotherapy medications with negative PETCT and positive CA15-3 relapsed after a
      median time of 158 days compared to patients who were negative for both tests and
      who were free from disease for at least 1 year. CONCLUSIONS: Our results showed
      that serial increases in CA15-3 can be used to predict positive PETCT results in
      BC patients during follow-up. Increased levels of CA15-3 may be considered an
      early warning sign in patients needing accurate molecular imaging investigations,
      as they are at higher risk of recurrence. In cases of elevated levels, multiple
      lesions or liver involvement may exist. Also, patients receiving chemotherapeutic
      or anti-hormonal treatment who have negative PETCT scans and increased CA15-3
      serum levels should be considered at risk for relapse, because the CA15-3-linked
      biochemical signal of the presence of a tumor can predict positive metabolic
      imaging.

PMID- 24886520
TI  - Barriers and enablers to delivery of the Healthy Kids Check: an analysis informed
      by the Theoretical Domains Framework and COM-B model.
AB  - BACKGROUND: More than a fifth of Australian children arrive at school
      developmentally vulnerable. To counteract this, the Healthy Kids Check (HKC), a
      one-off health assessment aimed at preschool children, was introduced in 2008
      into Australian general practice. Delivery of services has, however, remained
      low. The Theoretical Domains Framework, which provides a method to understand
      behaviours theoretically, can be condensed into three core components:
      capability, opportunity and motivation, and the COM-B model. Utilising this
      system, this study aimed to determine the barriers and enablers to delivery of
      the HKC, to inform the design of an intervention to promote provision of HKC
      services in Australian general practice. METHODS: Data from 6 focus group
      discussions with 40 practitioners from general practices in socio-culturally
      diverse areas of Melbourne, Victoria, were analysed using thematic analysis.
      RESULTS: Many practitioners expressed uncertainty regarding their capabilities
      and the practicalities of delivering HKCs, but in some cases HKCs had acted as a
      catalyst for professional development. Key connections between immunisation
      services and delivery of HKCs prompted practices to have systems of recall and
      reminder in place. Standardisation of methods for developmental assessment and
      streamlined referral pathways affected practitioners' confidence and motivation
      to perform HKCs. CONCLUSION: Application of a systematic framework effectively
      demonstrated how a number of behaviours could be targeted to increase delivery of
      HKCs. Interventions need to target practice systems, the support of office staff
      and referral options, as well as practitioners' training. Many behavioural
      changes could be applied through a single intervention programme delivered by the
      primary healthcare organisations charged with local healthcare needs (Medicare
      Locals) providing vital links between general practice, community and the health
      of young children.

PMID- 24886521
TI  - Association between tobacco and alcohol use among young adult bar patrons: a
      cross-sectional study in three cities.
AB  - BACKGROUND: Bars and nightclubs are key public venues where young adults
      congregate and use both tobacco and alcohol, and young adult bar patrons are at
      high risk for substance use. This study examined the association between
      cigarette smoking and alcohol use among a random sample of young adult bar
      patrons from three different cities in the USA. METHODS: Cross-sectional data was
      collected from a random sample of young adult bar patrons aged 18-29 in San
      Diego, CA (N = 1,150), Portland, ME (N = 1,019), and Tulsa, OK (N = 1,106) from
      2007-2010 (response rate 88%) using randomized time location sampling.
      Respondents reported the number of days they smoked cigarettes, drank alcohol,
      and binge drank in the past 30 days. Multinomial logistic regression was used to
      analyze the association between smoking (nonsmoker, occasional smoker, and
      regular smoker) and drinking and binge drinking for each city controlling for
      age, gender, race/ethnicity, and education. Predicted probabilities of each
      smoking category were calculated by drinking and binge drinking status. The
      association between smoking and drinking and binge drinking among combined
      samples was also analyzed, controlling for demographic variables and city.
      RESULTS: Respondents reported high current smoking rates, ranging from 51% in
      Portland to 58% in Tulsa. Respondents in Tulsa were more likely to report regular
      smoking than those in San Diego and Portland, with demographic variables being
      controlled. Young adult bar patrons also exhibited a strong association between
      smoking and drinking. In general, as the frequency of drinking and binge drinking
      increased, the predicted probability of being a smoker, especially a regular
      smoker, increased in each city. CONCLUSIONS: Young adult bar patrons consistently
      reported a high smoking rate and a strong relationship between smoking and
      drinking, regardless of the different bar cultures and tobacco control contexts
      in each of the three cities. While smoke-free bar policies were negatively
      associated with regular smoking, these policies alone may not be enough to
      influence the association between smoking and drinking, particularly if tobacco
      marketing continues in these venues, or in the absence of programs specifically
      addressing the co-use of tobacco and alcohol.

PMID- 24886522
TI  - Insight into model mechanisms through automatic parameter fitting: a new
      methodological framework for model development.
AB  - BACKGROUND: Striking a balance between the degree of model complexity and
      parameter identifiability, while still producing biologically feasible
      simulations using modelling is a major challenge in computational biology. While
      these two elements of model development are closely coupled, parameter fitting
      from measured data and analysis of model mechanisms have traditionally been
      performed separately and sequentially. This process produces potential mismatches
      between model and data complexities that can compromise the ability of
      computational frameworks to reveal mechanistic insights or predict new behaviour.
      In this study we address this issue by presenting a generic framework for
      combined model parameterisation, comparison of model alternatives and analysis of
      model mechanisms. RESULTS: The presented methodology is based on a combination of
      multivariate metamodelling (statistical approximation of the input-output
      relationships of deterministic models) and a systematic zooming into biologically
      feasible regions of the parameter space by iterative generation of new
      experimental designs and look-up of simulations in the proximity of the measured
      data. The parameter fitting pipeline includes an implicit sensitivity analysis
      and analysis of parameter identifiability, making it suitable for testing
      hypotheses for model reduction. Using this approach, under-constrained model
      parameters, as well as the coupling between parameters within the model are
      identified. The methodology is demonstrated by refitting the parameters of a
      published model of cardiac cellular mechanics using a combination of measured
      data and synthetic data from an alternative model of the same system. Using this
      approach, reduced models with simplified expressions for the
      tropomyosin/crossbridge kinetics were found by identification of model components
      that can be omitted without affecting the fit to the parameterising data. Our
      analysis revealed that model parameters could be constrained to a standard
      deviation of on average 15% of the mean values over the succeeding parameter
      sets. CONCLUSIONS: Our results indicate that the presented approach is effective
      for comparing model alternatives and reducing models to the minimum complexity
      replicating measured data. We therefore believe that this approach has
      significant potential for reparameterising existing frameworks, for
      identification of redundant model components of large biophysical models and to
      increase their predictive capacity.

PMID- 24886524
TI  - Neonatal systemic inflammation in rats alters retinal vessel development and
      simulates pathologic features of retinopathy of prematurity.
AB  - BACKGROUND: Alteration of retinal angiogenesis during development leads to
      retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of
      visual impairment in children. A number of clinical studies have reported higher
      rates of ROP in infants who had perinatal infections or inflammation, suggesting
      that exposure of the developing retina to inflammation may disturb retinal vessel
      development. Thus, we investigated the effects of systemic inflammation on
      retinal vessel development and retinal inflammation in neonatal rats. METHODS: To
      induce systemic inflammation, we intraperitoneally injected 100 MUl
      lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat
      pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days
      7 and 14, and subjected to assays for retinal vessels, inflammatory cells and
      molecules, and apoptosis. RESULTS: We found that intraperitoneal injection of LPS
      impaired retinal vessel development by decreasing vessel extension, reducing
      capillary density, and inducing localized overgrowth of abnormal retinal vessels
      and dilated peripheral vascular ridge, all of which are characteristic findings
      of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were
      localized in the lesion of abnormal vessels. Further analysis revealed that the
      number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi
      cells in the retina was higher in LPS-treated rats compared to controls.
      Similarly, the levels of TNF-alpha, IL-1beta, and IL-12a were increased in LPS
      treated retina. Also, apoptosis was increased in the inner retinal layer where
      retinal vessels are located. CONCLUSIONS: Our data demonstrate that systemic LPS
      induced inflammation elicits retinal inflammation and impairs retinal
      angiogenesis in neonatal rats, implicating perinatal inflammation in the
      pathogenesis of ROP.

PMID- 24886525
TI  - Using perceptive computing in multiple sclerosis - the Short Maximum Speed Walk
      test.
AB  - BACKGROUND: We investigated the applicability and feasibility of perceptive
      computing assisted gait analysis in multiple sclerosis (MS) patients using
      Microsoft KinectTM. To detect the maximum walking speed and the degree of spatial
      sway, we established a computerized and observer-independent measure, which we
      named Short Maximum Speed Walk (SMSW), and compared it to established clinical
      measures of gait disability in MS, namely the Expanded Disability Status Scale
      (EDSS) and the Timed 25-Foot Walk (T25FW). METHODS: Cross-sectional study of 22
      MS patients (age mean +/- SD 43 +/- 9 years, 13 female) and 22 age and gender
      matched healthy control subjects (HC) (age 37 +/- 11 years, 13 female). The
      disability level of each MS patient was graded using the EDSS (median 3.0, range
      0.0-6.0). All subjects then performed the SMSW and the Timed 25-Foot Walk
      (T25FW). The SMSW comprised five gait parameters, which together assessed average
      walking speed and gait stability in different dimensions (left/right, up/down and
      3D deviation). RESULTS: SMSW average walking speed was slower in MS patients (1.6
      +/- 0.3 m/sec) than in HC (1.8 +/- 0.4 m/sec) (p = 0.005) and correlated well
      with EDSS (Spearman's Rho 0.676, p < 0.001). Furthermore, SMSW revealed higher
      left/right deviation in MS patients compared to HC. SMSW showed high recognition
      quality and retest-reliability (covariance 0.13 m/sec, ICC 0.965, p < 0.001).
      There was a significant correlation between SMSW average walking speed and T25FW
      (Pearson's R = -0.447, p = 0.042). CONCLUSION: Our data suggest that ambulation
      tests using Microsoft KinectTM are feasible, well tolerated and can detect
      clinical gait disturbances in patients with MS. The retest-reliability was on par
      with the T25FW.

PMID- 24886526
TI  - Female breast cancer survival in Qidong, China, 1972-2011: a population-based
      study.
AB  - BACKGROUND: Based on data from the population-based Qidong Cancer Registry, we
      report a survival analysis for female breast cancer patients diagnosed during
      1972-2011 in order to assess the long-term trends for the prognosis of this
      cancer. METHODS: The last follow-up for survival status of the 3,398 registered
      female breast cancer cases was April, 2012. Cumulative observed survival (OS) and
      relative survival (RS) rates were calculated using Hakulinen's method performed
      by the SURV3.01 Software developed at the Finnish Cancer Registry. RESULTS: The
      one-, three-, five-, ten-, fifteen-, twenty-, thirty-, and forty- year OS rates
      were 83.61%, 67.53%, 58.75%, 48.56%, 42.57%, 38.30%, 29.19%, 19.35%; and the RS
      rates were 84.76%, 70.45%, 63.12%, 56.81%, 55.26%, 56.36%, 62.59%, 84.00%,
      respectively. Five-year RS rates of age groups 15-34, 35-44, 45-54, 55-64, 65-74,
      and 75+ were 60.17%, 68.27%, 67.79%, 56.03%, 55.50%, and 57.28%; 10-year RS rates
      were 54.16%, 59.59%, 61.34%, 47.78%, 51.30%, and 59.28%, respectively. There were
      statistical differences among the age groups (RS: chi2 = 152.15, P = 0.000).
      Remarkable improvement could be seen for the 5-year RS rates from 52.08% in 1972
      to 69.26% in 2003-2007, and the 10-year RS rates from 43.16% in 1972 to 60.85% in
      1998-2002, respectively. CONCLUSIONS: Survival outcomes from Qidong registered
      cases with breast cancer have shown gradual progress during the past 40 years.
      The disparities between survival rates of this area and developed countries are
      getting narrower, but there is still great need for improving survival in Qidong.

PMID- 24886528
TI  - Neuromyelitis optica presenting with relapses under treatment with natalizumab: a
      case report.
AB  - INTRODUCTION: Neuromyelitis optica is an inflammatory demyelinating disease of
      the central nervous system. To date, optimal therapeutic approaches for
      neuromyelitis optica have yet to be defined. Natalizumab is highly effective in
      relapsing-remitting multiple sclerosis and might be considered as an option. CASE
      PRESENTATION: Here, we describe a 67-year-old Caucasian man with definite
      neuromyelitis optica with detection of anti-aquaporin-4 antibodies over the
      course of the disease. After initially discussing the diagnosis of multiple
      sclerosis at an outside hospital, our patient received interferon beta 1a as well
      as repeated corticosteroid pulses without success. Under subsequent therapy with
      natalizumab, he continued to present relapses. It was not until discontinuation
      of natalizumab, repeated cycles of plasma exchanges and initiation of therapy
      with rituxan that the disease course started to stabilize. Although B cells were
      completely depleted, our patient experienced another severe myelitis relapse
      during further follow-up and an additional immunosuppressive therapy with
      cyclophosphamide was started. Under this regimen, no further relapses occurred
      over the next 24 months. CONCLUSIONS: This case adds further evidence to the
      previously discussed notion that natalizumab, while highly effective in multiple
      sclerosis, may not work sufficiently in neuromyelitis optica. It further
      advocates for repetitive testing of anti-aquaporin-4 antibodies before and after
      treatment initiation.

PMID- 24886523
TI  - MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress.
AB  - Over three decades have passed since the first report on the expression of CA125
      by ovarian tumors. Since that time our understanding of ovarian cancer biology
      has changed significantly to the point that these tumors are now classified based
      on molecular phenotype and not purely on histological attributes. However, CA125
      continues to be, with the recent exception of HE4, the only clinically reliable
      diagnostic marker for ovarian cancer. Many large-scale clinical trials have been
      conducted or are underway to determine potential use of serum CA125 levels as a
      screening modality or to distinguish between benign and malignant pelvic masses.
      CA125 is a peptide epitope of a 3-5 million Da mucin, MUC16. Here we provide an
      in-depth review of the literature to highlight the importance of CA125 as a
      prognostic and diagnostic marker for ovarian cancer. We focus on the increasing
      body of literature describing the biological role of MUC16 in the progression and
      metastasis of ovarian tumors. Finally, we consider previous and on-going efforts
      to develop therapeutic approaches to eradicate ovarian tumors by targeting MUC16.
      Even though CA125 is a crucial marker for ovarian cancer, the exact structural
      definition of this antigen continues to be elusive. The importance of MUC16/CA125
      in the diagnosis, progression and therapy of ovarian cancer warrants the need for
      in-depth research on the biochemistry and biology of this mucin. A renewed focus
      on MUC16 is likely to culminate in novel and more efficient strategies for the
      detection and treatment of ovarian cancer. 

PMID- 24886527
TI  - Predictors of sickness absence in college and university educated self-employed:
      a historic register study.
AB  - BACKGROUND: Despite a large proportion of the workforce being self-employed, few
      studies have been conducted on risk factors for sickness absence in this
      population. The aim of this study is to identify risk factors for future sickness
      absence in a population of college and university educated self-employed.
      METHODS: In a historic register study based on insurance company files risk
      factors were identified by means of logistic regression analysis. Data collected
      at application for private disability insurance from 634 applicants were related
      to subsequent sickness absence periods of 30 days or more during a follow-up
      period of 7.95 years. Variables studied were self-reported lifestyle variables,
      variables concerning medical history and present health conditions and variables
      derived from the general medical examination including blood tests and urinary
      analysis. RESULTS: Results from analysis of data from 634 applicants for private
      disability insurance show that previous periods of sickness absence (OR 2.07),
      female gender (OR 2.04), health complaints listed in the health declaration (OR
      1.88), elevated erythrocyte sedimentation rate (ESR) (OR 4.05) and the nature of
      the profession were related to a higher risk of sickness absence. CONCLUSIONS:
      Sickness absence was found to be related to demographic variables (gender,
      profession), medical variables (health complaints and erythrocyte sedimentation
      rate) and to variables with both a medical and a behavioural component (previous
      sickness absence).

PMID- 24886529
TI  - Determinants of maternal health service utilization in Ethiopia: analysis of the
      2011 Ethiopian Demographic and Health Survey.
AB  - BACKGROUND: Antenatal Care (ANC), use of skilled delivery attendants and
      postnatal care (PNC) services are key maternal health services that can
      significantly reduce maternal mortality. Understanding the factors that affect
      service utilization helps to design appropriate strategies and policies towards
      improvement of service utilization and thereby reduce maternal mortality. The
      objective of this study was to identify factors that affect utilization of
      maternal health services in Ethiopia. METHODS: Data were drawn from the 2011
      Ethiopia Demographic and Health Survey. The dependent variables were use of ANC,
      skilled delivery attendants and PNC services. The independent variables were
      categorized as socio-cultural, perceived needs and accessibility related factors.
      Data analysis was done using SPSS for windows version 20.0. Bivariate and
      multivariate logistic regression models were used in the analysis. RESULTS:
      Thirty four percent of women had ANC visits, 11.7% used skilled delivery
      attendants and 9.7% of women had a postnatal health checkup. Education of women,
      place of residence, ethnicity, parity, women's autonomy and household wealth had
      a significant association with the use of maternal health services. Women who
      completed higher education were more likely to use ANC (AOR = 3.8, 95% CI = 1.8
      7.8), skilled delivery attendants (AOR = 3.4, 95% CI = 1.9-6.2) and PNC (AOR =
      3.2, 95% CI = 2.0-5.2). Women from urban areas use ANC (AOR = 2.3, 95% CI = 1.9
      2.9), skilled delivery attendants (AOR = 4.9, 95% CI = 3.8-6.3) and PNC services
      (AOR = 2.6, 95% CI = 2.0-3.4) more than women from rural areas. Women who have
      had ANC visits during the index pregnancy were more likely to subsequently use
      skilled delivery attendants (AOR = 1.3, 95% CI = 1.1-1.7) and PNC (AOR = 3.4, 95%
      CI = 2.8-4.1). Utilization of ANC, delivery and PNC services is more among more
      autonomous women than those whose spending is controlled by other people.
      CONCLUSION: Maternal health service utilization in Ethiopia is very low. Socio
      demographic and accessibility related factors are major determinants of service
      utilization. There is a high inequality in service utilization among women with
      differences in education, household wealth, autonomy and residence. ANC is an
      important entry point for subsequent use of delivery and PNC services. Strategies
      that aim improving maternal health service utilization should target improvement
      of education, economic status and empowerment of women.

PMID- 24886530
TI  - Long-term result of posterolateral fusion of the lumbar spine using the Tadpole
      system.
AB  - BACKGROUND: Failure of pedicle screw fixation is often seen in patients with
      severe osteoporosis. We developed new lumbar spinal instrumentation (Tadpole
      system) for elderly patients who have osteoporotic bone and poor general health
      status. The objective of this study was to document the long-term clinical
      outcomes after Tadpole system fixation, the rate of spinal fusion, the incidence
      of adjacent segment degeneration, the rate of instrumentation failure, and the
      overall complications. METHODS: Sixty patients who underwent posterolateral
      spinal fusion using the Tadpole system, in whom a radiograph of the lumbar spine
      was taken at more than 5 years after operation, were involved in this study. The
      improvement rate of the Japanese Orthopaedic Association (JOA) score, rate of
      spinal fusion, presence or absence of adjacent segment degeneration, rate of
      instrumentation failure, and postoperative complications of each patient were
      assessed at 5 years postoperatively. RESULTS: The mean JOA score improvement was
      72.5%, and the posterolateral spinal fusion rate was 93.3% (56 of 60 patients) at
      the last follow-up. Adjacent segment degeneration occurred in only two patients
      who showed decreased intervertebral disc height, and instrumentation failure
      (hook deviation) was observed in one patient. No other complications were
      observed in any patients. CONCLUSION: Tadpole system fixation shows favorable
      long-term clinical outcomes.

PMID- 24886531
TI  - Cardiovascular outcome associations among cardiovascular magnetic resonance
      measures of arterial stiffness: the Dallas heart study.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) has been validated for the
      noninvasive assessment of total arterial compliance and aortic stiffness, but
      their associations with cardiovascular outcomes is unknown. The purpose of this
      study was to evaluate associations of CMR measures of total arterial compliance
      and two CMR measures of aortic stiffness with respect to future cardiovascular
      events. METHODS: The study consisted of 2122 Dallas Heart Study participants
      without cardiovascular disease who underwent CMR at 1.5 Tesla. Aortic stiffness
      was measured by CMR-derived ascending aortic distensibility and aortic arch pulse
      wave velocity. Total arterial compliance was calculated by dividing left
      ventricular stroke volume by pulse pressure. Participants were monitored for
      cardiovascular death, non-fatal cardiac events, and non-fatal extra-cardiac
      vascular events over 7.8 +/- 1.5 years. Cox proportional hazards regression was
      used to assess for associations between CMR measures and cardiovascular events.
      RESULTS: Age, systolic blood pressure, and resting heart rate were independently
      associated with changes in ascending aortic distensibility, arch pulse wave
      velocity, and total arterial compliance (all p < .0001). A total of 153
      participants (6.9%) experienced a cardiovascular event. After adjusting for
      traditional risk factors, total arterial compliance was modestly associated with
      increased risk for composite events (HR 1.07 per 1SD, p = 0.03) while the
      association between ascending aortic distensibility and composite events trended
      towards significance (HR 1.18 per 1SD, p = 0.08). Total arterial compliance and
      aortic distensibility were independently associated with nonfatal cardiac events
      (HR 1.11 per 1SD, p = 0.001 and HR 1.45 per 1SD, p = 0.0005, respectively), but
      not with cardiovascular death or nonfatal extra-cardiac vascular events. Arch
      pulse wave velocity was independently associated with nonfatal extra-cardiac
      vascular events (HR 1.18 per 1SD, p = 0.04) but not with cardiovascular death or
      nonfatal cardiac events. CONCLUSIONS: In a multiethnic population free of
      cardiovascular disease, CMR measures of arterial stiffness are associated with
      future cardiovascular events. Total arterial compliance and aortic distensibility
      may be stronger predictors of nonfatal cardiac events, while pulse wave velocity
      may be a stronger predictor of nonfatal extra-cardiac vascular events.

PMID- 24886533
TI  - Study flow diagrams in Cochrane systematic review updates: an adapted PRISMA flow
      diagram.
AB  - Cochrane systematic reviews are conducted and reported according to rigorous
      standards. A study flow diagram must be included in a new review, and there is
      clear guidance from the PRISMA statement on how to do this. However, for a review
      update, there is currently no guidance on how study flow diagrams should be
      presented. To address this, a working group was formed to find a solution and
      produce guidance on how to use these diagrams in review updates.A number of
      different options were devised for how these flow diagrams could be used in
      review updates, and also in cases where multiple searches for a review or review
      update have been conducted. These options were circulated to the Cochrane
      information specialist community for consultation and feedback. Following the
      consultation period, the working group refined the guidance and made the
      recommendation that for review updates an adapted PRISMA flow diagram should be
      used, which includes an additional box with the number of previously included
      studies feeding into the total. Where multiple searches have been conducted, the
      results should be added together and treated as one set of results.There is no
      existing guidance for using study flow diagrams in review updates. Our adapted
      diagram is a simple and pragmatic solution for showing the flow of studies in
      review updates. 

PMID- 24886532
TI  - Systematic study of the effects of lowering low-density lipoprotein-cholesterol
      on regression of coronary atherosclerotic plaques using intravascular ultrasound.
AB  - BACKGROUND: Conflicting results currently exist on the effects of LDL-C levels
      and statins therapy on coronary atherosclerotic plaque, and the target level of
      LDL-C resulting in the regression of the coronary atherosclerotic plaques has not
      been settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from
      Jan. 2000 to Jan. 2014 for randomized controlled or blinded end-points trials
      assessing the effects of LDL-C lowering therapy on regression of coronary
      atherosclerotic plaque (CAP) in patients with coronary heart disease by
      intravascular ultrasound. Data concerning the study design, patient
      characteristics, and outcomes were extracted. The significance of plaques
      regression was assessed by computing standardized mean difference (SMD) of the
      volume of CAP between the baseline and follow-up. SMD were calculated using fixed
      or random effects models. RESULTS: Twenty trials including 5910 patients with
      coronary heart disease were identified. Mean lowering LDL-C by 45.4% and to level
      66.8 mg/dL in the group of patients with baseline mean LDL-C 123.7 mg/dL, mean
      lowering LDL-C by 48.8% and to level 60.6 mg/dL in the group of patients with
      baseline mean LDL-C 120 mg/dL, and mean lowering LDL-C by 40.4% and to level 77.8
      mg/dL in the group of patients with baseline mean LDL-C 132.4 mg/dL could
      significantly reduce the volume of CAP at follow up (SMD -0.108 mm3, 95% CI 
      0.176 ~ -0.040, p = 0.002; SMD -0.156 mm3, 95% CI -0.235 ~ -0.078, p = 0.000; SMD
      -0.123 mm3, 95% CI -0.199 ~ -0.048, p = 0.001; respectively). LDL-C lowering by
      rosuvastatin (mean 33 mg daily) and atorvastatin (mean 60 mg daily) could
      significantly decrease the volumes of CAP at follow up (SMD -0.162 mm3, 95% CI: 
      0.234 ~ -0.081, p = 0.000; SMD -0.101, 95% CI: -0.184 ~ -0.019, p = 0.016;
      respectively). The mean duration of follow up was from 17 ~ 21 months.
      CONCLUSIONS: Intensive lowering LDL-C (rosuvastatin mean 33 mg daily and
      atorvastatin mean 60 mg daily) with >17 months of duration could lead to the
      regression of CAP, LDL-C level should be reduced by >40% or to a target level <78
      mg/dL for regressing CAP.

PMID- 24886534
TI  - Histopathological evaluation of non-melanoma skin cancer.
AB  - BACKGROUND: Non-melanoma skin cancers (NMSCs) are the most frequently seen
      cancers worldwide. METHODS: The medical records of patients diagnosed with basal
      cell carcinoma (BCC) and squamous cell carcinoma (SCC) in Hatay Antakya pathology
      laboratory between January 2010 and September 2012 were retrospectively included
      in the study. Tumors were categorized according to age, gender, anatomical
      localization, type, solitary-multiplicity, tumor diameter (0 to 2 mm, 2.1 to 6 mm
      and >6.1 mm), and presence of ulceration (BCCs), and morphological subtype,
      histopatological features and grades (SCCs). RESULTS: A total of 136 tumors in
      127 NMSC cases were examined. Solitary tumors were seen in 118 (92.9%), and
      multiple tumors in 9 (7.1%) patients. Mean age of the patients was 68.5 +/- 13
      years. BCC was observed in 96 (75.6%) and SCC in 31 (24.4%) patients. Mean
      diameter of all types of solitary and multiple tumors was 7.42 +/- 3.49 mm.
      Nodular subtype focal cystic changes were observed in 49 (47.6%) patients. All
      tumors (solitary and multiple) were seen on the face (67.6%), scalp (11.8%), and
      ear (11%). Well differentiated SCCs were detected in 20 cases (64.5%); ulceration
      was observed in 58.1% of all tumors. CONCLUSIONS: Epidemiologic and
      histopathological investigations, routine skin scanning performed on the elderly
      population and dermatological examination will help to improve efficient health
      applications.

PMID- 24886535
TI  - IL-33 is negatively associated with the BMI and confers a protective
      lipid/metabolic profile in non-diabetic but not diabetic subjects.
AB  - OBJECTIVE: Recent studies have demonstrated a protective role for IL-33 against
      obesity-associated inflammation, atherosclerosis and metabolic abnormalities. IL
      33 promotes the production of T helper type 2 (Th2) cytokines, polarizes
      macrophages towards a protective alternatively activated phenotype, reduces lipid
      storage and decreases the expression of genes associated with lipid metabolism
      and adipogenesis. Our objective was to determine the level of serum IL-33 in non
      diabetic and diabetic subjects, and to correlate these levels with clinical (BMI
      and body weight) and metabolic (serum lipids and HbA1c) parameters. METHODS: The
      level of IL-33 was measured in the serum of lean, overweight and obese non
      diabetic and diabetic subjects, and then correlated with clinical and metabolic
      parameters. RESULTS: Non-lean subjects had significantly (P = 0.01) lower levels
      of IL-33 compared to lean controls. IL-33 was negatively correlated with the BMI
      and body weight in lean and overweight, but not obese (non-diabetic and
      diabetic), subjects. IL-33 is associated with protective lipid profiles, and is
      negatively correlated with HbA1c, in non-diabetic (lean, overweight and obese)
      but not diabetic subjects. CONCLUSIONS: Our data support previous findings
      showing a protective role for IL-33 against adiposity and atherosclerosis, and
      further suggest that reduced levels of IL-33 may put certain individuals at
      increased risk of developing atherosclerosis and insulin resistance. Therefore,
      IL-33 may serve as a novel marker to predict those who may be at increased risk
      of developing atherosclerosis.

PMID- 24886536
TI  - The effect of adjunctive chlorhexidine mouthrinse on GCF MMP-8 and TIMP-1 levels
      in gingivitis: a randomized placebo-controlled study.
AB  - BACKGROUND: The aim of the present study was to evaluate the effect of adjunctive
      chlorhexidine (CHX) mouthrinse on gingival crevicular fluid (GCF) MMP-8 and TIMP
      1 levels in plaque-associated gingivitis. METHODS: A total of 50 gingivitis
      patients were included in the present study. In addition to daily plaque control,
      CHX group rinsed with CHX, while placebo group rinsed with placebo mouthrinse for
      4 weeks. GCF samples were collected, and clinical parameters including plaque
      index, papillary bleeding index, calculus index and pocket depth were recorded at
      baseline and 4 weeks. GCF MMP-8 and TIMP-1 levels were determined by
      immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA),
      respectively. RESULTS: In both groups, GCF MMP-8 levels of anterior and posterior
      sites at four weeks were not different from baseline (p > 0.05). There were no
      significant differences in GCF MMP-8 levels between the study groups at four
      weeks (p > 0.05). GCF TIMP-1 levels of anterior and posterior sites at four weeks
      were higher compared to baseline in both groups (p < 0.05). There was no
      significant difference in GCF TIMP level between the study groups at four weeks
      (p > 0.05). CONCLUSIONS: CHX usage had no significant effects on the GCF MMP-8
      and TIMP-1 levels in plaque-associate gingivitis. However, daily plaque control
      resulted in the increase of GCF TIMP-1 levels regardless of CHX usage.

PMID- 24886538
TI  - Dynamics of mRNA and polysomal abundance in early 3T3-L1 adipogenesis.
AB  - BACKGROUND: Adipogenesis is a complex process, in which immature pre-adipocytes
      change morphology, micro-anatomy and physiology to become mature adipocytes.
      These store and accumulate fat and release diverse hormones. Massive changes in
      protein content and protein composition of the transforming cell take place
      within a short time-frame.In a previous study we analyzed changes in the
      abundance of free and polysomal, i.e. ribosome bound, RNAs in the first hours of
      adipogenesis in the murine cell line 3T3-L1. Here we analyze changes of mRNA
      levels and their potential contribution to the changing protein pool by
      determination of mRNA levels and ribosome binding to mRNAs in 3T3-L1 cells
      stimulated for adipogenesis. We grouped mRNA species into categories with respect
      to up- or down-regulated transcription and translation and analyzed the groups
      regarding specific functionalities based on Gene Ontology (GO). RESULTS: A shift
      towards up-regulation of gene expression in early adipogenesis was detected.
      Genes up-regulated at the transcriptional (TC:up) and translational (TL:up) level
      (TC:up/TL:up) are very likely involved in control and logistics of translation.
      Many of them are known to contain a TOP motif. In the TC:up/TL:unchanged group we
      detected most of the metal binding proteins and metal transporters. In the
      TC:unchanged/TL:up group several factors of the olfactory receptor family were
      identified, while in TC:unchanged/TL:down methylation and repair genes are
      represented. In the TC:down/TL:up group we detected many signaling factors. The
      TC:down/TL:unchanged group mainly consists of regulatory factors. CONCLUSIONS:
      Within the first hours of adipogenesis, changes in transcriptional and
      translational regulation take place. Notably, genes with a specific biological or
      molecular function tend to cluster in groups according to their transcriptional
      and translational regulation.

PMID- 24886537
TI  - VAV3 mediates resistance to breast cancer endocrine therapy.
AB  - INTRODUCTION: Endocrine therapies targeting cell proliferation and survival
      mediated by estrogen receptor alpha (ERalpha) are among the most effective
      systemic treatments for ERalpha-positive breast cancer. However, most tumors
      initially responsive to these therapies acquire resistance through mechanisms
      that involve ERalpha transcriptional regulatory plasticity. Herein we identify
      VAV3 as a critical component in this process. METHODS: A cell-based chemical
      compound screen was carried out to identify therapeutic strategies against
      resistance to endocrine therapy. Binding to ERalpha was evaluated by molecular
      docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA-mediated
      protein depletion. Microarray analyses were performed to identify altered gene
      expression. Western blot analysis of signaling and proliferation markers, and
      shRNA-mediated protein depletion in viability and clonogenic assays, were
      performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed
      for association with the response to tamoxifen. Immunohistochemical analyses of
      VAV3 were carried out to determine its association with therapeutic response and
      different tumor markers. An analysis of gene expression association with drug
      sensitivity was carried out to identify a potential therapeutic approach based on
      differential VAV3 expression. RESULTS: The compound YC-1 was found to
      comparatively reduce the viability of cell models of acquired resistance. This
      effect was probably not due to activation of its canonical target (soluble
      guanylyl cyclase), but instead was likely a result of binding to ERalpha. VAV3
      was selectively reduced upon exposure to YC-1 or ERalpha depletion, and,
      accordingly, VAV3 depletion comparatively reduced the viability of cell models of
      acquired resistance. In the clinical scenario, germline variation in VAV3 was
      associated with the response to tamoxifen in Japanese breast cancer patients
      (rs10494071 combined P value = 8.4 * 10-4). The allele association combined with
      gene expression analyses indicated that low VAV3 expression predicts better
      clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was
      associated with poorer endocrine therapy response. Based on VAV3 expression
      levels and the response to erlotinib in cancer cell lines, targeting EGFR
      signaling may be a promising therapeutic strategy. CONCLUSIONS: This study
      proposes VAV3 as a biomarker and a rationale for its use as a signaling target to
      prevent and/or overcome resistance to endocrine therapy in breast cancer.

PMID- 24886539
TI  - Genetic polymorphism at an odorant receptor gene (Or39) among mosquitoes of the
      Anopheles gambiae complex in Senegal (West Africa).
AB  - BACKGROUND: Olfaction plays a significant role in insect behavior during critical
      steps of their life-cycle, such as host-seeking during foraging or the search for
      a mate. Here, we explored genetic polymorphism within and divergence between
      sibling species of the African malaria mosquito, Anopheles gambiae sensu lato in
      the gene sequence and encoded peptides of an odorant receptor, Or39. This study
      included sympatric specimens of An. gambiae sensu stricto, An. coluzzii and An.
      arabiensis sampled together in the village of Dielmo, Senegal. RESULTS: A 1,601
      bp genomic sequence composed of 6 exons and 5 introns was obtained for Or39 from
      6-8 mosquitoes in each of the 3 species. DNA sequence analysis revealed a high
      level of molecular polymorphism (pi = 0.0154; Haplotype diversity = 0.867) and
      high overall genetic differentiation between taxa (Fst > 0.92, P < 0.01). In
      total, 50 parsimony informative sites were recorded. Throughout the whole
      dataset, there were 13 non-synonymous mutations resulting in aminoacid changes in
      the encoded protein. Each of the 6 different identified peptides was species
      specific and none was shared across species. Most aminoacid changes were located
      on the intracellular domains of the protein. However, intraspecific polymorphisms
      in An. gambiae and An. arabiensis as well as species-specific mutations also
      occurred in the first extracellular domain. CONCLUSIONS: Although obtained from a
      limited number of specimens, our results point towards genetic differences
      between cryptic species within the An. gambiae complex in a gene of biological
      relevance that might be of evolutionary significance when exposed to disruptive
      selective forces.

PMID- 24886540
TI  - Self-rated dental health and dental insurance: modification by household income.
AB  - BACKGROUND: Previous studies have reported that socioeconomically disadvantaged
      Australians have poorer self-rated dental health (SRDH), are less likely to be
      insured for dental services and are less likely to have regular dental visits
      than their more advantaged counterparts. However, less is known about the
      associations between dental insurance and SRDH. The aim of this study was to
      examine the associations between SRDH and dental insurance status and to test if
      the relationship was modified by household income. METHODS: A random sample of
      3,000 adults aged 30-61 years was drawn from the Australian Electoral Roll and
      mailed a self-complete questionnaire. Analysis included dentate participants.
      Bivariate associations were assessed between SRDH and insurance stratified by
      household income group. A multiple variable model adjusting for covariates
      estimated prevalence ratios (PR) of having good to excellent SRDH and included an
      interaction term for insurance and household income group. RESULTS: The response
      rate was 39.1% (n = 1,093). More than half (53.9%) of the participants were
      insured and 72.5% had good to excellent SRDH. SRDH was associated with age group,
      brushing frequency, insurance status and income group. Amongst participants in
      the $40,000- < $80,000 income group, the insured had a higher proportion
      reporting good to excellent SRDH (80.8%) than the uninsured (66.5%); however,
      there was little difference in SRDH by insurance status for those in the
      $120,000+ income group. After adjusting for covariates, there was a significant
      interaction (p < 0.05) between having insurance and income; there was an
      association between insurance and SRDH for adults in the $40,000- < $80,000
      income group, but not for adults in higher income groups. CONCLUSIONS: For lower
      socio-economic groups being insured was associated with better SRDH, but there
      was no association for those in the highest income group. Insurance coverage may
      have the potential to improve dental health for low income groups.

PMID- 24886541
TI  - Virologic characterization of genotype 4 hepatitis C virus variants in patients
      treated with telaprevir.
AB  - BACKGROUND: Study C210 was a Phase IIa, exploratory trial to assess the activity
      of telaprevir on hepatitis C virus (HCV) early viral kinetics in treatment-naive
      patients infected with genotype 4 (G4) HCV. METHODS: Patients were randomized to
      receive peginterferon and ribavirin alone, telaprevir monotherapy (T arm), or
      telaprevir in combination with peginterferon/ribavirin (TPR arm) for 15 days,
      followed by a 46- or 48-week standard treatment phase. The current analysis aimed
      to characterize the genotype and phenotype of HCV G4 variants emerging during
      telaprevir treatment. RESULTS: Five of the 8 (62.5%) patients in the telaprevir
      (T) arm had viral breakthrough (vBT) during the investigational treatment phase
      (between baseline and Day 15), compared to no patients in the TPR arm. HCV G4
      viral variants with a T54A/T mutation were detected in two of these patients, as
      well as two other patients with detectable HCV RNA at the end of telaprevir
      treatment. Emergence of the T54A/T mutation was associated with a 2- to 4-fold
      decreased susceptibility to telaprevir. All patients with vBT during the
      investigational treatment phase or with a T54A/T mutation achieved undetectable
      HCV RNA 12 or 24 weeks after end of treatment with subsequent
      peginterferon/ribavirin treatment. CONCLUSIONS: In this analysis in G4 HCV
      infected patients, more patients in the telaprevir monotherapy arm experienced
      vBT with resistant variants compared to none with telaprevir combination therapy.
      The most commonly selected mutation T54A in telaprevir-treated G4 HCV patients
      was previously described in the context of G1 infection. TRIAL REGISTRATION: The
      trial was registered with ClinicalTrials.gov (NCT00580801).

PMID- 24886542
TI  - Different angiotensin receptor blockers and incidence of diabetes: a nationwide
      population-based cohort study.
AB  - BACKGROUND: Angiotensin receptor blockers (ARBs) have been shown to exert various
      peroxisome proliferator-activated receptor gamma (PPARgamma) binding activities
      and insulin-sensitizing effects. The objective of this study was to investigate
      the association of different ARBs with new-onset diabetes mellitus. METHODS: In
      the respective cohort, a total of 492,530 subjects who initiated ARB treatment
      between January 2004 and December 2009 were identified from Taiwan National
      Health Insurance Database. The primary outcome was newly diagnosed diabetes,
      defined as at least one hospital admission or two or more outpatient visits
      within a year with an ICD-9-CM code 250. Cox proportional regression was used to
      estimate the risk of diabetes associated with each ARB, using losartan as the
      reference. RESULTS: A total of 65,358 incident diabetes cases were identified out
      of 1,771,173 person-years. Olmesartan initiators had a small but significantly
      increased risk of developing diabetes after adjusting for baseline
      characteristics and mean daily dose (hazard ratio [HR], 1.07; 95% confidence
      interval [CI], 1.03-1.12). After excluding those followed for less than one year,
      the increase in diabetes risk are more pronounced (HR, 1.09; 95% CI, 1.05-1.14).
      This association was consistent across all subgroup analyses. Similar results
      were observed when a more strict definition of diabetes combining both diabetes
      diagnosis and anti-diabetic treatment was used. On the other hand, there was no
      difference in diabetes risk between telmisartan and losartan. CONCLUSIONS: Among
      all ARBs, olmesartan might be associated with a slightly increased risk of
      diabetes mellitus. Our data suggest differential diabetes risks associated with
      ARBs beyond a class effect.

PMID- 24886543
TI  - Dehydroepiandrosterone modulates the inflammatory response in a bilateral femoral
      shaft fracture model.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) has been shown to have immunomodulatory
      effects after hemorrhage and sepsis. The present study analyzes whether DHEA is
      also involved in the mediation of inflammatory stimuli induced by bilateral
      femoral shaft fracture. METHODS: Male C57/BL6 mice (6 per group) were subjected
      to closed bilateral femoral shaft fracture with intramedullary nailing followed
      by administration of either 25 mg/kg/24 h DHEA diluted in saline with 0.1%
      ethanol or saline with 0.1% ethanol. The sham group was treated by isolated
      intramedullary nailing without fracture. Animals were sacrificed after 6, 24, or
      72 h. Serum TNFalpha, IL-1beta, IL-6, IL-10, MCP-1, and KC concentrations were
      measured by Bio-Plex ProTm analysis. Acute pulmonary inflammation was assessed by
      histology, pulmonary myeloperoxidase (MPO) activity, and pulmonary IL-6
      concentration. RESULTS: DHEA was associated with a decrease in the systemic
      inflammatory response induced by bilateral femoral fracture, especially systemic
      IL-6 (322.2 vs. 62.5 pg/mL; P = 0.01), IL-1beta (1,422.6 vs. 754.1 pg/mL; P =
      0.05), and MCP-1 (219.4 vs. 44.1 pg/mL; P >0.01) levels. No changes in pulmonary
      inflammation were measured. CONCLUSION: We conclude that DHEA may be a treatment
      option to reduce systemic inflammation following musculoskeletal injuries
      although the pulmonary inflammatory reaction was not affected.

PMID- 24886544
TI  - Elevated plasma thrombomodulin and angiopoietin-2 predict the development of
      acute kidney injury in patients with acute myocardial infarction.
AB  - INTRODUCTION: Acute kidney injury (AKI) following acute myocardial infarction
      (AMI) is associated with unfavorable prognosis. Endothelial activation and injury
      were found to play a critical role in the development of both AKI and AMI. This
      pilot study aimed to determine whether the plasma markers of endothelial injury
      and activation could serve as independent predictors for AKI in patients with
      AMI. METHODS: This prospective study was conducted from March 2010 to July 2012
      and enrolled consecutive 132 patients with AMI receiving percutaneous coronary
      intervention (PCI). Plasma levels of thrombomodulin (TM), von Willebrand factor
      (vWF), angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor
      (VEGF) were measured on day 1 of AMI. AKI was defined as elevation of serum
      creatinine of more than 0.3 mg/dL within 48 hours. RESULTS: In total, 13 out of
      132 (9.8%) patients with AMI developed AKI within 48 hours. Compared with
      patients without AKI, patients with AKI had increased plasma levels of Ang-2
      (6338.28 +/- 5862.77 versus 2412.03 +/- 1256.58 pg/mL, P = 0.033) and sTM (7.6 +/
      2.26 versus 5.34 +/- 2.0 ng/mL, P < 0.001), and lower estimated glomerular
      filtration rate (eGFR) (46.5 +/- 20.2 versus 92.5 +/- 25.5 mL/min/1.73 m2, P <
      0.001). Furthermore, the areas under the receiver operating curves demonstrated
      that plasma thrombomodulin (TM) and Ang-2 levels on day 1 of AMI had modest
      discriminative powers for predicting AKI development following AMI (0.796, P
      <0.001; 0.833, P <0.001; respectively). CONCLUSIONS: Endothelial activation,
      quantified by plasma levels of TM and Ang-2 may play an important role in
      development of AKI in patients with AMI.

PMID- 24886545
TI  - Unilateral hypoplastic kidney - a novel highly penetrant feature of familial
      juvenile hyperuricaemic nephropathy.
AB  - BACKGROUND: Familial juvenile hyperuricaemic nephropathy is a rare inherited
      nephropathy with genetic heterogeneity. Categorised by genetic defect, mutations
      in uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta (HNF-1beta)
      genes as well as linkage to chromosome 2p22.1-21 have previously been identified.
      Knowledge of the genetics of this phenotype has provided important clues to
      developmental pathways in the kidney. CASE PRESENTATION: We report a novel
      phenotype, with the typical features of hyperuricemia and renal deterioration,
      but with the additional unexpected feature of unilateral renal hypoplasia.
      Mutation analyses of the existing known genes and genetic loci were negative
      indicating a new monogenic cause. Interestingly two cousins of the index case did
      not share the latter feature, suggesting a modifier gene effect. CONCLUSION:
      Unilateral renal hypo/aplasia is usually sporadic and relatively common, with no
      genetic cause to date identified. This reported pedigree reveals the possibility
      that a new, unknown renal developmental gene may be implicated in the FJHN
      phenotype.

PMID- 24886546
TI  - How to set up and manage a trainee-led research collaborative.
AB  - BACKGROUND: Ensuring that doctors in training acquire sufficient knowledge,
      experience and understanding of medical research is a universal and longstanding
      issue which has been brought into sharper focus by the growth of evidence based
      medicine. All healthcare systems preparing doctors in training for practice have
      to balance the acquisition of specific clinical attitudes, knowledge and skills
      with the wider need to ensure doctors are equipped to remain professionally
      competent as medical science advances. Most professional medical bodies
      acknowledge that this requires trainee doctors to experience some form of
      research education, not only in order to carry out original research, but to
      acquire sufficient academic skills to become accomplished research consumers in
      order to remain informed throughout their professional practice. There are many
      barriers to accomplishing this ambitious aim. DISCUSSION: This article briefly
      explains why research collaboratives are necessary, describes how to establish a
      collaborative, and recommends how to run one. It is based on the experiences of
      the pioneering West Midlands Research Collaborative and draws on the wider
      literature about the organisation and delivery of high quality research projects.
      Practical examples of collaborative projects are given to illustrate the
      potential of this form of research organisation. SUMMARY: The new trainee-led
      research collaboratives provide a supportive framework for planning, ownership
      and delivery of high quality multicentre research. This ensures clinical
      relevance, increases the chances of research findings being translated into
      changes in practice and should lead to improved patient outcomes. Research
      collaboratives also enhance the research skills and extend the scientific
      horizons of doctors in training.

PMID- 24886547
TI  - Comparison of performance of Sri Lankan and US children on cognitive and motor
      scales of the Bayley scales of infant development.
AB  - BACKGROUND: There is no validated scale to assess neurodevelopment of infants and
      children in Sri Lanka. The Bayley III scales have used widely globally but it has
      not been validated for Sri Lankan children. We administered the Cognitive and
      Motor Scales of the Bayley III to 150 full-term children aged 6, 12 and 24 months
      from the Gampaha District of Sri Lanka. We compared the performance of Sri Lankan
      children 6, 12 and 24 months of age on the cognitive and motor scales of the
      Bayley III with that of US children. RESULTS: Compared to the US norms, at 12
      months, Sri Lankan children had significantly higher cognitive scores and lower
      gross motor scores, and at 24 months significantly lower cognitive scores. The
      test had a high test-retest reliability among Sri Lankan children. CONCLUSIONS:
      There were small differences in the cognitive and motors scores between Sri
      Lankan and US children. It is feasible to use Bayley III scales to assess
      neurodevelopment of Sri Lankan children. However, we recommend that the tool be
      validated using a larger representative sample of all population groups.

PMID- 24886548
TI  - Long term follow up and retrospective study on 533 gastric cancer cases.
AB  - BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death in
      China and the outcome of GC patients is poor. The aim of the research is to study
      the prognostic factors of gastric cancer patients who had curative intent or
      palliative resection, completed clinical database and follow-up. METHODS: This
      retrospective study analyzed 533 GC patients from three tertiary referral
      teaching hospitals from January 2004 to December 2010 who had curative intent or
      palliative resection, complete clinical database and follow-up information. The
      GC-specific overall survival (OS) status was determined by the Kaplan-Meier
      method, and univariate analysis was conducted to identify possible factors for
      survival. Multivariate analysis using the Cox proportional hazard model and a
      forward regression procedure was conducted to define independent prognostic
      factors. RESULTS: By the last follow-up, the median follow-up time of 533 GC
      patients was 38.6 mo (range 6.9-100.9 mo), and the median GC-specific OS was 25.3
      mo (95% CI: 23.1-27.4 mo). The estimated 1-, 2-, 3- and 5-year GC-specific OS
      rates were 78.4%, 61.4%, 53.3% and 48.4%, respectively. Univariate analysis
      identified the following prognostic factors: hospital, age, gender, cancer site,
      surgery type, resection type, other organ resection, HIPEC, LN status, tumor
      invasion, distant metastases, TNM stage, postoperative SAE, systemic chemotherapy
      and IP chemotherapy. In multivariate analysis, seven factors were identified as
      independent prognostic factors for long term survival, including resection type,
      HIPEC, LN status, tumor invasion, distant metastases, postoperative SAE and
      systemic chemotherapy. CONCLUSIONS: Resection type, HIPEC, postoperative SAE and
      systemic chemotherapy are four independent prognostic factors that could be
      intervened for GC patients for improving survival.

PMID- 24886550
TI  - Quantitative analysis of lung elastic fibers in idiopathic pleuroparenchymal
      fibroelastosis (IPPFE): comparison of clinical, radiological, and pathological
      findings with those of idiopathic pulmonary fibrosis (IPF).
AB  - BACKGROUND: The pathological appearance of idiopathic pleuroparenchymal
      fibroelastosis (IPPFE) with hematoxylin-eosin staining is similar to that of
      usual interstitial pneumonia (UIP) in patients with idiopathic pulmonary fibrosis
      (IPF). The amount of elastic fibers (EF) and detailed differences between IPPFE
      and IPF have not been fully elucidated. The aim of this study was to quantify the
      EF and identify the differences between IPPFE and IPF. METHODS: We evaluated six
      patients with IPPFE and 28 patients with IPF who underwent surgical lung biopsy
      or autopsy. The patients' clinical history, physical findings, chest high
      resolution computed tomography (HRCT) findings, and pathological features of lung
      specimens were retrospectively evaluated. The amounts of EF in lung specimens
      were quantified with Weigert's staining using a camera with a charge-coupled
      device and analytic software in both groups. RESULTS: Fewer patients with IPPFE
      than IPF had fine crackles (50.0% vs. 96.4%, p = 0.012). Patients with IPPFE had
      a lower forced vital capacity (62.7 +/- 10.9% vs. 88.6 +/- 21.9% predicted, p =
      0.009), higher consolidation scores on HRCT (1.7 +/- 0.8 vs. 0.3 +/- 0.5, p <
      0.0001), lower body mass indices (17.9 +/- 0.9 vs. 24.3 +/- 2.8, p < 0.0001), and
      more pneumothoraces than did patients with IPF (66.7 vs. 3.6%, p = 0.002). Lung
      specimens from patients with IPPFE had more than twice the amount of EF than did
      those from patients with IPF (28.5 +/- 3.3% vs. 12.1 +/- 4.4%, p < 0.0001). The
      amount of EF in the lower lobes was significantly lower than that in the upper
      lobes, even in the same patient with IPPFE (23.6 +/- 2.4% vs. 32.4 +/- 5.5%, p =
      0.048). However, the amount of EF in the lower lobes of patients with IPPFE was
      still higher than that of patients with IPF (23.6 +/- 2.4% vs. 12.2 +/- 4.4%, p <
      0.0001). CONCLUSION: More than twice the amount of EF was found in patients with
      IPPFE than in those with IPF. Even in the lower lobes, the amount of EF was
      higher in patients with IPPFE than in those with IPF, although the distribution
      of lung EF was heterogeneous in IPPFE specimens.

PMID- 24886549
TI  - Impact of additional counselling sessions through phone calls on smoking
      cessation outcomes among smokers in Penang State, Malaysia.
AB  - BACKGROUND: Studies all over the world reported that smoking relapses occur
      during the first two weeks after a quit date. The current study aimed to assess
      the impact of the additional phone calls counselling during the first month on
      the abstinence rate at 3 and 6 months after quit date among smokers in Penang,
      Malaysia. METHODS: The study was conducted at Quit Smoking Clinic of two major
      hospitals in Penang, Malaysia. All the eligible smokers who attended the clinics
      between February 1st and October 31st 2012 were invited. Participants were
      randomly assigned by using urn design method either to receive the usual care
      that followed in the clinics (control) or the usual care procedure plus extra
      counselling sessions through phone calls during the first month of quit attempt
      (intervention). RESULTS: Participants in our cohort smoked about 14 cigarettes
      per day on average (mean = 13.78 +/- 7.0). At 3 months, control group was less
      likely to quit smoking compared to intervention group (36.9% vs. 46.7%, verified
      smoking status) but this did not reach statistical significance (OR = 0.669; 95%
      CI = 0.395-1.133, P = 0.86). However, at 6 months, 71.7% of the intervention
      group were successfully quit smoking (bio-chemically verified) compared to 48.6%
      of the control group (P < 0.001). The control group were significantly less
      likely to quit smoking (OR = 0.375; 95% CI = 0.217-0.645, P < 0.001).
      CONCLUSIONS: Smoking cessation intervention consisting of phone calls counselling
      delivered during the first month of quit attempt revealed significantly higher
      abstinence rates compared with a standard care approach. Therefore, the
      additional counselling in the first few weeks after stop smoking is a promising
      treatment strategy that should be evaluated further. TRIAL REGISTRATION:
      TCTR20140504001.

PMID- 24886551
TI  - Allelic expression analysis of the osteoarthritis susceptibility locus that maps
      to chromosome 3p21 reveals cis-acting eQTLs at GNL3 and SPCS1.
AB  - BACKGROUND: An osteoarthritis (OA) susceptibility locus has been mapped to
      chromosome 3p21, to a region of high linkage disequilibrium encompassing twelve
      genes. Six of these genes are expressed in joint tissues and we therefore
      assessed whether any of the six were subject to cis-acting regulatory
      polymorphisms active in these tissues and which could therefore account for the
      association signal. METHODS: We measured allelic expression using pyrosequencing
      assays that can distinguish mRNA output from each allele of a transcript single
      nucleotide polymorphism. We assessed RNA extracted from the cartilage and other
      joint tissues of OA patients who had undergone elective joint replacement
      surgery. A two-tailed Mann-Whitney exact test was used to test the significance
      of any allelic differences. RESULTS: GNL3 and SPCS1 demonstrated significant
      allelic expression imbalance (AEI) in OA cartilage (GNL3, mean AEI = 1.04, p =
      0.0002; SPCS1, mean AEI = 1.07, p < 0.0001). Similar results were observed in
      other tissues. Expression of the OA-associated allele was lower than that of the
      non-associated allele for both genes. CONCLUSIONS: cis-acting regulatory
      polymorphisms acting on GNL3 and SPCS1 contribute to the OA association signal at
      chromosome 3p21, and these genes therefore merit further investigation.

PMID- 24886553
TI  - Selective and flexible depletion of problematic sequences from RNA-seq libraries
      at the cDNA stage.
AB  - BACKGROUND: A major hurdle to transcriptome profiling by deep-sequencing
      technologies is that abundant transcripts, such as rRNAs, can overwhelm the
      libraries, severely reducing transcriptome-wide coverage. Methods for depletion
      of such unwanted sequences typically require treatment of RNA samples prior to
      library preparation, are costly and not suited to unusual species and
      applications. Here we describe Probe-Directed Degradation (PDD), an approach that
      employs hybridisation to DNA oligonucleotides at the single-stranded cDNA library
      stage and digestion with Duplex-Specific Nuclease (DSN). RESULTS: Targeting
      Saccharomyces cerevisiae rRNA sequences in Illumina HiSeq libraries generated by
      the split adapter method we show that PDD results in efficient removal of rRNA.
      The probes generate extended zones of depletion as a function of library insert
      size and the requirements for DSN cleavage. Using intact total RNA as starting
      material, probes can be spaced at the minimum anticipated library size minus 20
      nucleotides to achieve continuous depletion. No off-target bias is detectable
      when comparing PDD-treated with untreated libraries. We further provide a
      bioinformatics tool to design suitable PDD probe sets. CONCLUSION: We find that
      PDD is a rapid procedure that results in effective and specific depletion of
      unwanted sequences from deep-sequencing libraries. Because PDD acts at the cDNA
      stage, handling of fragile RNA samples can be minimised and it should further be
      feasible to remediate existing libraries. Importantly, PDD preserves the original
      RNA fragment boundaries as is required for nucleotide-resolution footprinting or
      base-cleavage studies. Finally, as PDD utilises unmodified DNA oligonucleotides
      it can provide a low-cost option for large-scale projects, or be flexibly
      customised to suit different depletion targets, sample types and organisms.

PMID- 24886552
TI  - Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial.
AB  - BACKGROUND: Polyphenols may lower the risk of cardiovascular disease (CVD) and
      other chronic diseases due to their antioxidant and anti-inflammatory properties,
      as well as their beneficial effects on blood pressure, lipids and insulin
      resistance. However, no previous epidemiological studies have evaluated the
      relationship between the intake of total polyphenols intake and polyphenol
      subclasses with overall mortality. Our aim was to evaluate whether polyphenol
      intake is associated with all-cause mortality in subjects at high cardiovascular
      risk. METHODS: We used data from the PREDIMED study, a 7,447-participant,
      parallel-group, randomized, multicenter, controlled five-year feeding trial aimed
      at assessing the effects of the Mediterranean Diet in primary prevention of
      cardiovascular disease. Polyphenol intake was calculated by matching food
      consumption data from repeated food frequency questionnaires (FFQ) with the
      Phenol-Explorer database on the polyphenol content of each reported food. Hazard
      ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and
      mortality were estimated using time-dependent Cox proportional hazard models.
      RESULTS: Over an average of 4.8 years of follow-up, we observed 327 deaths. After
      multivariate adjustment, we found a 37% relative reduction in all-cause mortality
      comparing the highest versus the lowest quintiles of total polyphenol intake
      (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the
      polyphenol subclasses, stilbenes and lignans were significantly associated with
      reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04
      and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no
      significant associations apparent in the rest (flavonoids or phenolic acids).
      CONCLUSIONS: Among high-risk subjects, those who reported a high polyphenol
      intake, especially of stilbenes and lignans, showed a reduced risk of overall
      mortality compared to those with lower intakes. These results may be useful to
      determine optimal polyphenol intake or specific food sources of polyphenols that
      may reduce the risk of all-cause mortality. CLINICAL TRIAL REGISTRATION:
      ISRCTN35739639.

PMID- 24886554
TI  - Downregulation of microRNA-182-5p contributes to renal cell carcinoma
      proliferation via activating the AKT/FOXO3a signaling pathway.
AB  - BACKGROUND: Emerging evidence has suggested that dysregulation of miR-182-5p may
      contribute to tumor development and progression in several types of human
      cancers. However, its role in renal cell carcinoma (RCC) is still unknown.
      METHODS: Quantitative RT-PCR was used to quantify miR-182-5p expression in RCC
      clinical tissues. Bisulfite sequencing PCR was used for DNA methylation analysis.
      The CCK-8, colony formation, flow cytometry, and a xenograft model were
      performed. Immunohistochemistry was conducted using the peroxidase and DAB
      methods. A miR-182-5p target was determined by luciferase reporter assays,
      quantitative RT-PCR, and Western blotting. RESULTS: miR-182-5p is frequently down
      regulated in human RCC tissues. Epigenetic modulation may be involved in the
      regulation of miR-182-5p expression. Enforced expression of miR-182-5p in RCC
      cells significantly inhibited the proliferation and tumorigenicity in vitro and
      in vivo. Additionally, overexpression of miR-182-5p induced G1-phase arrest via
      inhibition of AKT/FOXO3a signaling. Moreover, FLOT1 was confirmed as a target of
      miR-182-5p. Silencing FLOT1 by small interfering RNAs phenocopied the effects of
      miR-182-5p overexpression, whereas restoration of FLOT1 in miR-182-5p 
      overexpressed RCC cells partly reversed the suppressive effects of miR-182-5p.
      CONCLUSIONS: These findings highlight an important role for miR-182-5p in the
      pathogenesis of RCC, and restoration of miR-182-5p could be considered as a
      potential therapeutic strategy for RCC therapy.

PMID- 24886555
TI  - Comparison of face-to-face versus email guided self-help for binge eating: study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Guided self-help is a recommended first-step treatment for bulimia
      nervosa, binge eating disorder and atypical variants of these disorders. Further
      research is needed to compare guided self-help that is delivered face-to-face
      versus via email. METHODS/DESIGN: This clinical trial uses a randomised,
      controlled design to investigate the effectiveness of providing guided self-help
      either face-to-face or via e-mail, also using a delayed treatment control
      condition. At least 17 individuals are required per group, giving a minimum N of
      51. DISCUSSION: Symptom outcomes will be assessed and estimates of cost
      effectiveness made. Results are proposed to be disseminated locally and
      internationally (through submission to conferences and peer-reviewed journals),
      and will hopefully inform local service provision. The trial has been approved by
      an ethics review board and was registered with ClinicalTrials.gov NCT01832792 on
      9 April 2013.

PMID- 24886556
TI  - Meniscal tear as potential steering factor for inflammation may aggravate
      arthritis: two case reports.
AB  - INTRODUCTION: Meniscal tear is thought to play a crucial role in onset as well as
      progression of arthritis. However, role of cytokine response to meniscal injury
      and resulting inflammation is not clearly understood. Because synovial fluid is
      juxtaposed to cartilage and serves as a biological connection between
      chondrocytes and synoviocytes, we chose synovial fluid analysis to ascertain
      biochemical response associated with a meniscal tear. CASE PRESENTATION: We
      report the cases of two patients with clinically different inflammatory
      arthritis, both of whom are Indian men. Patient 1 was 30 years of age, and
      patient 2 was 50 years of age. They both had a history of meniscal tear, which we
      confirmed by magnetic resonance imaging scans. Synovial fluid samples obtained
      from these two patients were analyzed for proinflammatory markers, such as
      interleukin 1beta (IL-1beta) and nitric oxide, and also for glycosaminoglycan as
      a cartilage degradation indicator. Relatively high levels of IL-1beta (2000.0 +/-
      15.7 pg/ml) and nitric oxide (4.73 +/- 0.05 MUM/ml) and relatively low
      glycosaminoglycan (93.75 +/- 6.3 MUg/ml) were observed in patient 1,
      corroborating the diagnosis of traumatic meniscal tear. Compared to patient 1,
      Patient 2 had relatively low levels of IL-1beta (54.55 +/- 14.5 pg/ml) and nitric
      oxide (20.00 +/- 0.6 MUM/ml) and remarkably high glycosaminoglycan levels (553.33
      +/- 1.7 MUg/ml), coupled with significant osteophytes and profound cartilage
      loss, which indicated severe arthritis and a diagnosis of degenerative meniscal
      tear. CONCLUSION: The elevated levels of inflammatory IL-1beta aggravated the
      severity of arthritis attributable to meniscal tear in both patients, as found in
      follow-up visits. This was quite evident in patient 2, whereas patient 1, being
      younger, had less serious symptoms. Meniscal tear has emerged as a potential
      confounding factor in arthritis with different clinical backgrounds, which leads
      to increased levels of inflammation and results in accelerated disease
      progression.

PMID- 24886557
TI  - Anti-feeding efficacy of Activyl(r) Tick Plus topical treatment of dogs against
      Phlebotomus perniciosus.
AB  - BACKGROUND: Topical permethrin treatment is known to prevent feeding of sandflies
      on dogs. This study investigated the anti-feeding efficacy and the immediate
      insecticidal efficacy (knock-down effect) of topical treatment of dogs with a new
      commercially available combination of indoxacarb and permethrin (Activyl(r) Tick
      Plus), compared with a negative control. METHODS: Sedated dogs were individually
      exposed to unfed female sandflies in a darkened chamber for one hour 2, 7, 14, 21
      and 29 days after treatment. Mean fly feeding and survival rates in the two
      groups after one hour of exposure were used to calculate the anti-feeding
      efficacy and the knock-down effect, respectively. RESULTS: On Days 2, 7, 14, 21
      and 29 post treatment, the anti-feeding efficacy was 99, 98, 96, 88 and 84% based
      on geometric means. The mean number of fed sandflies in the treated group was
      significantly lower than in the control group mean at every evaluation time
      point. The knock-down effect, measured at one hour after exposure of the flies to
      treated dogs, was 32, 27, 9, 0 and 4% based on geometric means, at the same time
      points. The number of dead flies was significantly higher in the treated group on
      Days 2 and 7 post-treatment. No adverse effects of treatment were observed at any
      time during the study. CONCLUSIONS: Activyl(r) Tick Plus treatment of dogs
      provided a high anti-feeding efficacy against Phlebotomus perniciosus from 2 to
      21 days post treatment, with continuing significant anti-feeding to 29 days post
      treatment, and was well tolerated. Some knock-down effect following one hour of
      exposure of flies to treated dogs was observed in the first week after treatment.

PMID- 24886558
TI  - Presentation, aetiology and treatment of adult intussusception in a tertiary Sub
      Saharan hospital: a 10-year retrospective study.
AB  - BACKGROUND: Adult intussusception is a rare clinical condition worldwide. It
      contributes to less than 5% of all cases of intussusception. Few studies have
      been conducted in low-income countries compared to high-income countries;
      particularly Sub-Saharan Africa. Based on anecdotal evidence, the authors
      hypothesized that the condition is not as rare in a Sub-Saharan setting in
      comparison with western countries. We set out to conduct the first review study
      of adult intussusception in Uganda. METHODS: The medical records of 37 (out of a
      total of 62 cases) adolescent and adult patients with a postoperative diagnosis
      of intussusception at Mulago National Referral and Teaching Hospital, from
      January 2003 to December 2012, were analyzed. The clinical features, diagnosis,
      treatment and pathologic features of lesions for these patients were reviewed.
      Intraoperative findings were described with reference to: the site of the
      intussusception, and the triggering lesion (either idiopathic or with a lead
      point). RESULTS: The mean age was 33.6 years, with a range of 13 - 72 years. The
      male to female ratio was 1.85:1. The mean number of days for which symptoms had
      been present prior to presentation was 6.3 days, while the median was 4 days. All
      37 patients presented with abdominal pain. Only 13 (35.1%) had the classical
      paediatric triad of abdominal pain, a palpable abdominal mass and bloody stool.
      Most of the remaining patients presented sub-acutely with non-specific symptoms.
      A lead point was present in 28 patients (75.7%). Of these, 24 (64.9%) cases
      involved tumours. Among the tumours, 54.2% were malignant. Treatment did not
      involve intussusception reduction in 14 patients (37.8%). Some form of operative
      surgery was conducted in 31 (83.8%) patients; mainly segmental bowel resections
      and hemi-colectomies. CONCLUSION: Adult intussusception is uncommon in the
      Uganda, though probably less so than in western countries. It presents sub
      acutely or chronically and is often diagnosed at laparotomy. Lead points are the
      triggering lesion most times and are due mainly to tumours. The bulk of tumours
      are malignant. Most patients require surgical resection, with prior reduction
      done in selected cases.

PMID- 24886559
TI  - Uncomplicated Plasmodium vivax malaria in pregnancy associated with mortality
      from acute respiratory distress syndrome.
AB  - The association between severe malaria and Plasmodium vivax species is
      contentious. On the Thai-Myanmar border, all pregnant women are followed
      systematically with active weekly malaria screening. Over a 27-year period of
      providing antenatal care, 48,983 have been prospectively followed until pregnancy
      outcome (miscarriage or delivery) and 4,298 women have had P. vivax detected at
      least once. Reported here is the first known P. vivax-associated death amongst
      these women. The initial patient presentation was of uncomplicated P. vivax (0.5%
      parasitaemia) in a term, multigravida woman who responded rapidly to oral
      artesunate and mefloquine treatment, clearing her blood stage parasites within 48
      hours. The patient appeared well, was ambulatory and due to be discharged but
      became unwell with acute respiratory distress syndrome (ARDS) requiring
      ventilation three days (67 hours) into treatment. Despite induction and delivery
      of a stillborn foetus, ventilatory requirements increased and the patient died on
      day 7. The patient had a low body mass index. Sensitive detection with nested PCR
      confirmed only the presence of P. vivax species and concomitant infections such
      as tuberculosis and human immunodeficiency virus (HIV) were also ruled out. The
      contemporaneous treatment of acute uncomplicated P. vivax and the onset of ARDS
      on day 3 in this patient implies a possible but unconfirmed association with
      death in this patient. Assuming this death was caused by P. vivax, the risk of
      ARDS-related maternal mortality in this setting did not differ significantly
      between Plasmodium falciparum and P. vivax (0.24 per 1,000 (1/4,158) versus 0.23
      per 1,000 (1/4,298), contrary to the increased risk of maternal mortality from P.
      falciparum compared to P. vivax, 2.89 per 1,000 (12/4,158) versus 0.23 per 1,000
      (1/4,298), P = 0.003.

PMID- 24886561
TI  - Comorbidity and prognostic indices do not improve the 5-year mortality prediction
      of components of comprehensive geriatric assessment in hospitalized older
      patients.
AB  - BACKGROUND: Advancing age is associated with increased vulnerability to chronic
      health problems. Identifying factors that predict oldest-old status is vital for
      developing effective clinical interventions and public health strategies.
      METHODS: Observational prospective study of patients aged 75 years and older
      consecutively admitted to an Acute Geriatric Ward of a tertiary hospital. After a
      comprehensive geriatric assessment all patients were assessed for five
      comorbidity indices and two prognostic models. Univariate and multivariate
      logistic regression models were fitted to assess the association between each
      score and 5-year mortality. The ability of each score to predict mortality was
      assessed using the area under the receiver operating characteristic curve.
      RESULTS: 122 patients were enrolled. All patients were followed up for five
      years. 90 (74%) of them died during the study period. In the logistic regression
      analyses, apart from age, cognitive impairment and Barthel Index, three indices
      were identified as statistically associated with 5-year mortality: the Geriatric
      Index of Comorbidity and the two prognostic indices. The multivariate model that
      combined age, sex, cognitive impairment and Barthel showed a good discriminate
      ability (AUC = 0.79), and it did not improve substantially after adding
      individually any of the indices. CONCLUSIONS: Some prognostic models and the
      Geriatric Index of Comorbidity are better than other widely used indices such as
      the Charlson Index in predicting 5-year mortality in hospitalized older patients,
      however, none of these indices is superior to some components of comprehensive
      geriatric assessment.

PMID- 24886560
TI  - Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic
      overlap with the lethal ciliopathy Meckel syndrome.
AB  - Joubert syndrome is a clinically and genetically heterogeneous ciliopathy
      characterized by a typical cerebellar and brainstem malformation (the "molar
      tooth sign"), and variable multiorgan involvement. To date, 24 genes have been
      found mutated in Joubert syndrome, of which 13 also cause Meckel syndrome, a
      lethal ciliopathy with kidney, liver and skeletal involvement. Here we describe
      four patients with mild Joubert phenotypes who carry pathogenic mutations in
      either MKS1 or B9D1, two genes previously implicated only in Meckel syndrome. 

PMID- 24886563
TI  - A stakeholder analysis of the perceived outcomes of developing and implementing
      England's obesity strategy 2008-2011.
AB  - BACKGROUND: International recommendations urge governments to implement
      population-based strategies to reduce the burden of obesity. This study assesses
      the development and implementation of the obesity strategy in England 2008-2011,
      Healthy Weight, Healthy Lives (HWHL). The aim was to identify if stakeholders
      perceived HWHL to have made any difference to the action to address obesity in
      England, with the ultimate objective of identifying insights that could inform
      the development and implementation of future obesity strategies in England and
      elsewhere. METHODS: Qualitative study using semi-structured interviews and
      thematic framework analysis. 40 stakeholders involved in the development and
      implementation of the obesity strategy were interviewed. RESULTS: Evidence from
      this study suggests that HWHL was perceived to have made a positive difference to
      efforts to address obesity in England. It was credited with creating political
      buy-in, engaging more stakeholders, stimulating and facilitating action,
      enhancing knowledge and changing attitudes. But it was reported to have failed to
      fully catalyse action across all government departments and sectors, or to
      develop adequate mechanisms for learning about the effectiveness of the different
      elements and actions in the Strategy. Key elements of the Strategy contributing
      towards to the perceived positive differences included its multi-faceted,
      inclusive nature; governance structures; monitoring programme to assess progress
      against national and local targets; child-focus; and funding. The development of
      the Strategy was said to be stimulated and aided by the prior synthesis of a
      critical mass of scientific evidence. CONCLUSIONS: The English experience of HWHL
      lends support to the recommendations to develop population-based obesity
      strategies. It indicates that in order to stimulate comprehensive, inter-sectoral
      action, obesity strategies need to take a population-based, multi-faceted
      approach, be implemented through a clear governance structure, follow a
      systematic process of aligning goals, objectives and agendas between government
      departments and sectors with a stake in obesity, and have a clear system of
      reporting changes in obesity rates against a target. In order to design effective
      policies and to build the case for continued investment, obesity strategies also
      need to incorporate a national framework for learning and evaluation from the
      outset.

PMID- 24886564
TI  - Objective classification of different head and neck positions and their influence
      on the radiographic pharyngeal diameter in sport horses.
AB  - BACKGROUND: Various head and neck positions in sport horses are significant as
      they can interfere with upper airway flow mechanics during exercise. Until now,
      research has focused on subjectively described head and neck positions. The
      objective of this study was to develop an objective, reproducible method for
      quantifying head and neck positions accurately. RESULTS: Determining the angle
      between the ridge of the nose and the horizontal plane (ground angle) together
      with the angle between the ridge of nose and the line connecting the neck and the
      withers (withers angle) has provided values that allow precise identification of
      three preselected head and neck positions for performing sport horses. The
      pharyngeal diameter, determined on lateral radiographs of 35 horses, differed
      significantly between the established flexed position and the remaining two head
      and neck positions (extended and neutral). There was a significant correlation
      between the pharyngeal diameter and the ground angle (Spearman's rank correlation
      coefficient -0.769, p < 0.01) as well as between the pharyngeal diameter and the
      withers angle (Spearman's rank correlation coefficient 0.774, p < 0.01).
      CONCLUSION: The combination of the ground angle and the withers angle is a
      suitable tool for evaluating and distinguishing frequently used head and neck
      positions in sport horses. The ground angle and the withers angle show
      significant correlation with the measured pharyngeal diameter in resting horses.
      Hence, these angles provide an appropriate method for assessing the degree of
      head and neck flexion. Further research is required to examine the influence of
      increasing head and neck flexion and the related pharyngeal diameter on upper
      airway function in exercising horses.

PMID- 24886562
TI  - SoxNeuro orchestrates central nervous system specification and differentiation in
      Drosophila and is only partially redundant with Dichaete.
AB  - BACKGROUND: Sox proteins encompass an evolutionarily conserved family of
      transcription factors with critical roles in animal development and stem cell
      biology. In common with vertebrates, the Drosophila group B proteins SoxNeuro and
      Dichaete are involved in central nervous system development, where they play both
      similar and unique roles in gene regulation. Sox genes show extensive functional
      redundancy across metazoans, but the molecular basis underpinning functional
      compensation mechanisms at the genomic level are currently unknown. RESULTS:
      Using a combination of genome-wide binding analysis and gene expression
      profiling, we show that SoxNeuro directs embryonic neural development from the
      early specification of neuroblasts through to the terminal differentiation of
      neurons and glia. To address the issue of functional redundancy and compensation
      at a genomic level, we compare SoxNeuro and Dichaete binding, identifying common
      and independent binding events in wild-type conditions, as well as instances of
      compensation and loss of binding in mutant backgrounds. CONCLUSIONS: We find that
      early aspects of group B Sox functions in the central nervous system, such as
      stem cell maintenance and dorsoventral patterning, are highly conserved. However,
      in contrast to vertebrates, we find that Drosophila group B1 proteins also play
      prominent roles during later aspects of neural morphogenesis. Our analysis of the
      functional relationship between SoxNeuro and Dichaete uncovers evidence for
      redundant and independent functions for each protein, along with unexpected
      examples of compensation and interdependency, thus providing new insights into
      the general issue of transcription factor functional redundancy.

PMID- 24886566
TI  - Impacts of hot and cold spells differ for acute and chronic ischaemic heart
      diseases.
AB  - BACKGROUND: Many studies have reported associations between temperature extremes
      and cardiovascular mortality but little has been understood about differences in
      the effects on acute and chronic diseases. The present study examines hot and
      cold spell effects on ischaemic heart disease (IHD) mortality in the Czech
      Republic during 1994-2009, with emphasis upon differences in the effects on acute
      myocardial infarction (AMI) and chronic IHD. METHODS: We use analogous
      definitions for hot and cold spells based on quantiles of daily average
      temperature anomalies, thus allowing for comparison of results for summer hot
      spells and winter cold spells. Daily mortality data were standardised to account
      for the long-term trend and the seasonal and weekly cycles. Periods when the data
      were affected by epidemics of influenza and other acute respiratory infections
      were removed from the analysis. RESULTS: Both hot and cold spells were associated
      with excess IHD mortality. For hot spells, chronic IHD was responsible for most
      IHD excess deaths in both male and female populations, and the impacts were much
      more pronounced in the 65+ years age group. The excess mortality from AMI was
      much lower compared to chronic IHD mortality during hot spells. For cold spells,
      by contrast, the relative excess IHD mortality was most pronounced in the younger
      age group (0-64 years), and we found different pattern for chronic IHD and AMI,
      with larger effects on AMI. CONCLUSIONS: The findings show that while excess
      deaths due to IHD during hot spells are mainly of persons with chronic diseases
      whose health had already been compromised, cardiovascular changes induced by cold
      stress may result in deaths from acute coronary events rather than chronic IHD,
      and this effect is important also in the younger population. This suggests that
      the most vulnerable population groups as well as the most affected cardiovascular
      diseases differ between hot and cold spells, which needs to be taken into account
      when designing and implementing preventive actions.

PMID- 24886565
TI  - Use of antagonists and morpholinos in loss-of-function analyses: estrogen
      receptor ESR2a mediates the effects of 17alpha-ethinylestradiol on primordial
      germ cell distribution in zebrafish.
AB  - BACKGROUND: Various chemicals released into the aquatic environment adversely
      affect the reproductive system of fish, particularly by changing gonad structure
      and function. 17alpha-ethinylestradiol (EE2) is a potent environmental estrogen
      that disrupts sexual differentiation and normal reproduction in fish. Previous
      studies have shown that exposure to endocrine-disrupting chemicals (EDCs)
      disrupts the migration of primordial germ cells (PGCs) in zebrafish. METHODS: To
      investigate the effects of EE2 exposure on PGC migration, zebrafish embryos were
      injected with gfp-nanos mRNA to label PGCs and subsequently exposed to different
      concentrations of EE2. Typical estrogen receptor antagonist treatment and
      morpholino knockdown experiments were used to identify functional estrogen
      receptors that mediate the effects of EE2. RESULTS: The migration of PGCs was
      disrupted after exposure to high concentrations of EE2 (1 mirog/L). Loss-of
      function analyses were performed for estrogen receptor ESR1, ESR2a, and ESR2b,
      and only loss of ESR2a resulted in a decreased number of ectopic PGCs following
      exposure to 1 mirog/L EE2. CONCLUSIONS: EE2 exposure disrupts PGC migration and
      distribution, and this effect is mediated through the estrogen receptor ESR2a.

PMID- 24886567
TI  - Strengthening district-based health reporting through the district health
      management information software system: the Ugandan experience.
AB  - BACKGROUND: Untimely, incomplete and inaccurate data are common challenges in
      planning, monitoring and evaluation of health sector performance, and health
      service delivery in many sub-Saharan African settings. We document Uganda's
      experience in strengthening routine health data reporting through the roll-out of
      the District Health Management Information Software System version 2 (DHIS2).
      METHODS: DHIS2 was adopted at the national level in January 2011. The system was
      initially piloted in 4 districts, before it was rolled out to all the 112
      districts by July 2012. As part of the roll-out process, 35 training workshops
      targeting 972 users were conducted throughout the country. Those trained included
      Records Assistants (168, 17.3%), District Health Officers (112, 11.5%), Health
      Management Information System Focal Persons (HMIS-FPs) (112, 11.5%), District
      Biostatisticians (107, 11%) and other health workers (473, 48.7%). To assess
      improvements in health reporting, we compared data on completeness and timeliness
      of outpatient and inpatient reporting for the period before (2011/12) and after
      (2012/13) the introduction of DHIS2. We reviewed data on the reporting of
      selected health service coverage indicators as a proxy for improved health
      reporting, and documented implementation challenges and lessons learned during
      the DHIS2 roll-out process. RESULTS: Completeness of outpatient reporting
      increased from 36.3% in 2011/12 to 85.3% in 2012/13 while timeliness of
      outpatient reporting increased from 22.4% to 77.6%. Similarly, completeness of
      inpatient reporting increased from 20.6% to 57.9% while timeliness of inpatient
      reporting increased from 22.5% to 75.6%. There was increased reporting on
      selected health coverage indicators (e.g. the reporting of one-year old children
      who were immunized with three doses of pentavelent vaccine increased from 57% in
      2011/12 to 87% in 2012/13). Implementation challenges included limited access to
      computers and internet (34%), inadequate technical support (23%) and limited
      worker force (18%). CONCLUSION: Implementation of DHIS2 resulted in improved
      timeliness and completeness in reporting of routine outpatient, inpatient and
      health service usage data from the district to the national level. Continued
      onsite support supervision and mentorship and additional system/infrastructure
      enhancements, including internet connectivity, are needed to further enhance the
      performance of DHIS2.

PMID- 24886568
TI  - Sick leave patterns in common musculoskeletal disorders--a study of doctor
      prescribed sick leave.
AB  - BACKGROUND: Comparative data on sick leave within musculoskeletal disorders
      (MSDs) is limited. Our objective was to give a descriptive overview of sick leave
      patterns in different MSDs. METHODS: Using electronic medical records, we
      collected information on dates and diagnostic codes for all available sick leave
      certificates, during 2 years (2009-2010), in the North Western part of the Skane
      region in Sweden (22 public primary health care centres and two general
      hospitals). Using the International Classification of Diseases (ICD) 10 codes on
      the certificates we studied duration, age and sex distribution and recurrent
      periods of sick leave for six strategically chosen MSDs; low back pain (M54) disc
      disorders (M51), knee osteoarthritis (M17) hip osteoarthritis (M16) rheumatoid
      arthritis (M05-M06) and myalgia (M79). RESULTS: All together 20 251 sick leave
      periods were issued for 16 673 individuals 16-64 years of age (53% women). Out of
      the selected disorders, low back pain and myalgia had the shortest sick leave
      periods, with a mean of 26 and 27 days, respectively, while disc disorders and
      rheumatoid arthritis had the longest periods with a mean of 150 and 147 days. For
      low back pain and myalgia 27% and 26% of all sick leave was short (8-14 days) and
      only 11% and 13%, were long (>=90 days). For the other selected MSDs, less than
      5% of the periods were short. For disc disorders, hip osteoarthritis and
      rheumatoid arthritis, more than 60% of the periods were long (p > 0.001). For
      back disorders and myalgia most periods were issued in the age groups between 40
      49, with similar patterns for women and men. Osteoarthritis and rheumatoid
      arthritis had most periods in the age groups of 50-64, and patterns for women and
      men differed. Low back pain, rheumatoid arthritis and myalgia had the greatest
      share of recurrent sick leave (31%, 34% and 32% respectively). CONCLUSION:
      Duration, age and sex distribution and numbers of recurrent sick leave varies
      considerably between different MSDs. This underscores the importance of using
      specified diagnosis, in sick leave research as well as in planning of treatment
      and rehabilitation and evaluation of prognosis.

PMID- 24886569
TI  - Continuous positive airway pressure for bronchiolitis in a general paediatric
      ward; a feasibility study.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is commonly used to
      relieve respiratory distress in infants with bronchiolitis, but has mostly been
      studied in an intensive care setting. Our prime aim was to evaluate the
      feasibility of CPAP for infants with bronchiolitis in a general paediatric ward,
      and secondary to assess capillary PCO2 (cPCO2) levels before and during
      treatment. METHODS: From May 1(st) 2008 to April 30(th) 2012, infants with
      bronchiolitis at Stavanger University Hospital were treated with CPAP in a
      general paediatric ward, but could be referred to an intensive care unit (ICU)
      when needed, according to in-house guidelines. Levels of cPCO2 were prospectively
      registered before the start of CPAP and at approximately 4, 12, 24 and 48 hours
      of treatment as long as CPAP was given. We had a continuous updating program for
      the nurses and physicians caring for the infants with CPAP. The study was
      population based. RESULTS: 672 infants (3.4%) were hospitalized with
      bronchiolitis. CPAP was initiated in 53 infants (0.3%; 7.9% of infants with
      bronchiolitis), and was well tolerated in all but three infants. 46 infants were
      included in the study, the majority of these (n = 33) were treated in the general
      ward only. These infants had lower cPCO2 before treatment (8.0; 7.7, 8.6)(median;
      quartiles) than those treated at the ICU (n = 13) (9.3;8.5, 9.9) (p < 0.001). The
      level of cPCO2 was significantly reduced after 4 h in both groups; 1.1 kPa
      (paediatric ward) (p < 0.001) and 1.3 kPa (ICU) (p = 0.002). Two infants on the
      ICU did not respond to CPAP (increasing cPCO2 and severe apnoe) and were given
      mechanical ventilation, otherwise no side effects were observed in either group
      treated with CPAP. CONCLUSION: Treatment with CPAP for infants with bronchiolitis
      may be feasible in a general paediatric ward, providing sufficient staffing and
      training, and the possibility of referral to an ICU when needed.

PMID- 24886570
TI  - Breast tuberculosis in northeast Iran: review of 22 cases.
AB  - BACKGROUND: Breast tuberculosis (breast TB) is an extremely rare disease, so case
      reviews are also rare. METHODS: This study is a retrospective review of patients
      with breast TB who were treated between 2002 and 2012 at the Health Center of
      Gorgan City. RESULTS: All 22 patients were females, their mean age was 32.4
      years, and all were new cases. Patients presented with swelling of the breast
      (22%), lump (55%) and excretion from the involved breast (27%), and breast pain
      (55%). The highest rate of breast TB occurred in 2011 (27%). All patients
      received the DOTS regimen for a mean duration of 7.3 +/- 0.7 months; in addition,
      segmental resection was performed on 11 patients (50%). CONCLUSIONS: The findings
      confirmed that breast TB in Iran should be considered as a differential diagnosis
      of breast masses. All patients in our study received the daily and 'Directly
      Observed Treatment Short-course' (DOTS) regimens. Anti-tubercular therapy for six
      months with or without minimal surgical intervention currently is the main
      treatment.

PMID- 24886571
TI  - Evidence-based decision-making in infectious diseases epidemiology, prevention
      and control: matching research questions to study designs and quality appraisal
      tools.
AB  - BACKGROUND: The Project on a Framework for Rating Evidence in Public Health
      (PRECEPT) was initiated and is being funded by the European Centre for Disease
      Prevention and Control (ECDC) to define a methodology for evaluating and grading
      evidence and strength of recommendations in the field of public health, with
      emphasis on infectious disease epidemiology, prevention and control. One of the
      first steps was to review existing quality appraisal tools (QATs) for individual
      research studies of various designs relevant to this area, using a question-based
      approach. METHODS: Through team discussions and expert consultations, we
      identified 20 relevant types of public health questions, which were grouped into
      six domains, i.e. characteristics of the pathogen, burden of disease, diagnosis,
      risk factors, intervention, and implementation of intervention. Previously
      published systematic reviews were used and supplemented by expert consultation to
      identify suitable QATs. Finally, a matrix was constructed for matching questions
      to study designs suitable to address them and respective QATs. Key features of
      each of the included QATs were then analyzed, in particular in respect to its
      intended use, types of questions and answers, presence/absence of a quality
      score, and if a validation was performed. RESULTS: In total we identified 21 QATs
      and 26 study designs, and matched them. Four QATs were suitable for experimental
      quantitative study designs, eleven for observational quantitative studies, two
      for qualitative studies, three for economic studies, one for diagnostic test
      accuracy studies, and one for animal studies. Included QATs consisted of six to
      28 items. Six of the QATs had a summary quality score. Fourteen QATs had
      undergone at least one validation procedure. CONCLUSIONS: The results of this
      methodological study can be used as an inventory of potentially relevant
      questions, appropriate study designs and QATs for researchers and authorities
      engaged with evidence-based decision-making in infectious disease epidemiology,
      prevention and control.

PMID- 24886573
TI  - Analyzing spatial clustering and the spatiotemporal nature and trends of HIV/AIDS
      prevalence using GIS: the case of Malawi, 1994-2010.
AB  - BACKGROUND: Although local spatiotemporal analysis can improve understanding of
      geographic variation of the HIV epidemic, its drivers, and the search for
      targeted interventions, it is limited in sub-Saharan Africa. Despite recent
      declines, Malawi's estimated 10.0% HIV prevalence (2011) remained among the
      highest globally. Using data on pregnant women in Malawi, this study 1) examines
      spatiotemporal trends in HIV prevalence 1994-2010, and 2) for 2010, identifies
      and maps the spatial variation/clustering of factors associated with HIV
      prevalence at district level. METHODS: Inverse distance weighting was used within
      ArcGIS Geographic Information Systems (GIS) software to generate continuous
      surfaces of HIV prevalence from point data (1994, 1996, 1999, 2001, 2003, 2005,
      2007, and 2010) obtained from surveillance antenatal clinics. From the surfaces
      prevalence estimates were extracted at district level and the results mapped
      nationally. Spatial dependency (autocorrelation) and clustering of HIV prevalence
      were also analyzed. Correlation and multiple regression analyses were used to
      identify factors associated with HIV prevalence for 2010 and their spatial
      variation/clustering mapped and compared to HIV clustering. RESULTS: Analysis
      revealed wide spatial variation in HIV prevalence at regional, urban/rural,
      district and sub-district levels. However, prevalence was spatially leveling out
      within and across 'sub-epidemics' while declining significantly after 1999.
      Prevalence exhibited statistically significant spatial dependence nationally
      following initial (1995-1999) localized, patchy low/high patterns as the epidemic
      spread rapidly. Locally, HIV "hotspots" clustered among eleven southern
      districts/cities while a "coldspot" captured configurations of six central region
      districts. Preliminary multiple regression of 2010 HIV prevalence produced a
      model with four significant explanatory factors (adjusted R2 = 0.688): mean
      distance to main roads, mean travel time to nearest transport, percentage that
      had taken an HIV test ever, and percentage attaining a senior primary education.
      Spatial clustering linked some factors to particular subsets of high HIV
      prevalence districts. CONCLUSIONS: Spatial analysis enhanced understanding of
      local spatiotemporal variation in HIV prevalence, possible underlying factors,
      and potential for differentiated spatial targeting of interventions. Findings
      suggest that intervention strategies should also emphasize improved access to
      health/HIV services, basic education, and syphilis management, particularly in
      rural hotspot districts, as further research is done on drivers at finer scale.

PMID- 24886572
TI  - Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2
      1, by treatment with highly bioavailable curcumin during an exploratory clinical
      trial.
AB  - BACKGROUND: The management of osteoarthritis (OA) remains a challenge. There is a
      need not only for safe and efficient treatments but also for accurate and
      reliable biomarkers that would help diagnosis and monitoring both disease
      activity and treatment efficacy. Curcumin is basically a spice that is known for
      its anti-inflammatory properties. In vitro studies suggest that curcumin could be
      beneficial for cartilage in OA. The aim of this exploratory, non-controlled
      clinical trial was to evaluate the effects of bio-optimized curcumin in knee OA
      patients on the serum levels of specific biomarkers of OA and on the evaluation
      of pain. METHODS: Twenty two patients with knee OA were asked to take 2x3
      caps/day of bio-optimized curcumin (Flexofytol(r)) for 3 months. They were
      monitored after 7, 14, 28 and 84 days of treatment. Pain over the last 24 hours
      and global assessment of disease activity by the patient were evaluated using a
      visual analog scale (100 mm). The serum levels of Coll-2-1, Coll-2-1NO2, Fib3-1,
      Fib3-2, CRP, CTX-II and MPO were determined before and after 14 and 84 days of
      treatment. RESULTS: The treatment with curcumin was globally well tolerated. It
      significantly reduced the serum level of Coll2-1 (p<0.002) and tended to decrease
      CRP. No other significant difference was observed with the other biomarkers. In
      addition, curcumin significantly reduced the global assessment of disease
      activity by the patient. CONCLUSION: This study highlighted the potential effect
      of curcumin in knee OA patient. This effect was reflected by the variation of a
      cartilage specific biomarker, Coll2-1 that was rapidly affected by the treatment.
      These results are encouraging for the qualification of Coll2-1 as a biomarker for
      the evaluation of curcumin in OA treatment. TRIAL REGISTRATION: NCT01909037 at
      clinicaltrials.gov.

PMID- 24886574
TI  - Efficacy and toxicity of chemoradiation in patients with anal cancer--a
      retrospective analysis.
AB  - BACKGROUND: Concurrent chemotherapy and radiation therapy is the preferred
      standard of care for patients with anal cancer. Several studies have suggested a
      benefit of intensity-modulated radiation therapy (IMRT) compared with 3D
      conformal radiation (3D-CRT) regarding acute toxicity. This study evaluates
      outcome and toxicity of patients undergoing IMRT/Tomotherapy or 3D-CRT at our
      institution. METHODS: A cohort of 105 anal cancer patients was treated with
      chemoradiation or radiation alone (16.2%) between January 2000 and December 2011.
      37 patients received 3D-CRT while 68 patients were treated with IMRT. Follow-up
      exams were performed every 3 to 6 months for a minimum of 3 years and then
      annually. RESULTS: Median follow-up was 41.4 months (2.8 - 158.4). Overall
      survival (OS), Progression-free survival (PFS) and local control (LC) at 3 years
      was 70.3%, 66.5%, 78.3% in the 3D-CRT group and 82.9%, 66.5%, 75.3% in the IMRT
      group without statistically significant difference. 3-year Colostomy-free
      survival (CFS) was 85.7% in the IMRT/Tomotherapy group and 91.8% in the 3D-CRT
      group (p = 0.48). No grade 4 toxicity was found in both groups. Severe (G2/3)
      acute skin toxicity (94.6% vs. 63.2%; p < 0.001) and acute gastrointestinal
      toxicity rate (67.6% vs. 47.1%; p = 0.03) was significantly higher with 3D-CRT
      compared to IMRT/Tomotherapy. CONCLUSION: The use of IMRT can reduce acute severe
      side effects of the skin and gastrointestinal tract but did not demonstrate
      improved results regarding OS, PFS, LC and CFS.

PMID- 24886576
TI  - Child feeding knowledge and practices among women participating in growth
      monitoring and promotion in Accra, Ghana.
AB  - BACKGROUND: Child undernutrition and poor feeding practices remain a concern in
      Ghana. The Growth Monitoring and Promotion (GMP) programme seeks to empower
      mothers to provide appropriate child care. Although the program has been
      implemented in Ghana for over four decades, little is known about its impact on
      child feeding outcomes. The current study assessed the association between GMP
      exposure and mothers' child feeding knowledge and practices in the Accra
      Metropolitan Area (AMA), Ghana. METHODS: A cross-sectional survey of 199 mother
      child pairs accessing child welfare services in six public health facilities in
      the AMA was conducted. A structured questionnaire was used to collect data on
      respondent characteristics and child feeding knowledge; a 24-hour dietary recall
      tool was used to record child feeding practices. Linear regression analysis was
      used to determine the association between mothers' exposure to GMP and their
      knowledge and practices on child feeding. RESULTS: Seventy four percent of
      mothers had not missed any scheduled child welfare clinic sessions. Over 60% of
      mothers knew the appropriate age of introduction of foods; 86% also gave correct
      response regarding minimum number of times their child should be fed daily. About
      81% of children less than 6 months were exclusively breastfed in the preceding 24
      hours, although 36% had received water since birth. Forty two percent of children
      6-23 months received dietary diverse meals while 64% were fed the required number
      of times in a day. Overall, only 32% of children 6-23 months received a minimum
      acceptable diet in the preceding 24 hours. A higher GMP exposure was positively
      associated with feeding knowledge scores among mothers with children below 6
      months (p < 0.05). CONCLUSION: Although most mothers were knowledgeable about
      recommendations, feeding practices were suboptimal, especially complementary
      feeding. GMP exposure was associated with feeding knowledge only among mothers
      with children less than 6 months. Strengthening of feeding counselling focused on
      children above 6 months is recommended.

PMID- 24886575
TI  - HIV-1 protease-induced apoptosis.
AB  - BACKGROUND: Apoptosis is one of the presumptive causes of CD4+ T cell depletion
      during HIV infection and progression to AIDS. However, the precise role of HIV-1
      in this process remains unexplained. HIV-1 protease (PR) has been suggested as a
      possible factor, but a direct link between HIV-1 PR enzymatic activity and
      apoptosis has not been established. RESULTS: Here, we show that expression of
      active HIV-1 PR induces death in HeLa and HEK-293 cells via the mitochondrial
      apoptotic pathway. This conclusion is based on in vivo observations of the direct
      localization of HIV-1 PR in mitochondria, a key player in triggering apoptosis.
      Moreover, we observed an HIV-1 PR concentration-dependent decrease in
      mitochondrial membrane potential and the role of HIV-1 PR in activation of
      caspase 9, PARP cleavage and DNA fragmentation. In addition, in vitro data
      demonstrated that HIV-1 PR mediates cleavage of mitochondrial proteins Tom22,
      VDAC and ANT, leading to release of AIF and Hsp60 proteins. By using yeast two
      hybrid screening, we also identified a new HIV-1 PR interaction partner, breast
      carcinoma-associated protein 3 (BCA3). We found that BCA3 accelerates p53
      transcriptional activity on the bax promoter, thus elevating the cellular level
      of pro-apoptotic Bax protein. CONCLUSION: In summary, our results describe the
      involvement of HIV-1 PR in apoptosis, which is caused either by a direct effect
      of HIV-1 PR on mitochondrial membrane integrity or by its interaction with
      cellular protein BCA3.

PMID- 24886578
TI  - Inflammatory pseudotumor of the liver diagnosed as metastatic liver tumor in a
      patient with a gastrointestinal stromal tumor of the rectum: report of a case.
AB  - BACKGROUND: Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion.
      A case of IPT of the liver found in association with a malignant gastrointestinal
      stromal tumor (GIST) is reported. CASE REPORT: A 74-year-old man was admitted to
      our hospital for a liver tumor. He previously underwent rectal amputation for a
      malignant GIST. Computed tomography (CT) revealed a low-density area in the liver
      and dynamic contrast-enhanced MRI (EOB-MRI) showed that the tumor was completely
      washed out in the delayed phase. 18Fluorine-fluorodeoxyglucose positron emission
      tomography (FDG-PET) showed strong uptake in the liver. A diagnosis of liver
      metastasis was made and partial hepatectomy was performed. Microscopic
      examination showed that the tumor was an IPT. CONCLUSION: Differential diagnosis
      between IPT and malignant neoplasms is difficult. Moreover, FDG-PET revealed
      strong uptake in the tumor. To our knowledge, this is the first patient reported
      to have an IPT in association with a rectal GIST. This patient is discussed along
      with a review of the literature.

PMID- 24886577
TI  - A wide range of pheromone-stimulated sexual and reproductive behaviors in female
      mice depend on G protein Galphao.
AB  - BACKGROUND: Optimal reproductive fitness is essential for the biological success
      and survival of species. The vomeronasal organ is strongly implicated in the
      display of sexual and reproductive behaviors in female mice, yet the roles that
      apical and basal vomeronasal neuron populations play in controlling these gender
      specific behaviors remain largely unclear. RESULTS: To dissect the neural
      pathways underlying these functions, we genetically inactivated the basal
      vomeronasal organ layer using conditional, cell-specific ablation of the G
      protein Galphao. Female mice mutant for Galphao show severe alterations in sexual
      and reproductive behaviors, timing of puberty onset, and estrous cycle. These
      mutant mice are insensitive to reproductive facilitation stimulated by male
      pheromones that accelerate puberty and induce ovulation. Galphao-mutant females
      exhibit a striking reduction in sexual receptivity or lordosis behavior to males,
      but gender discrimination seems to be intact. These mice also show a loss in male
      scent preference, which requires a learned association for volatile olfactory
      signals with other nonvolatile ownership signals that are contained in the high
      molecular weight fraction of male urine. Thus, Galphao impacts on both
      instinctive and learned social responses to pheromones. CONCLUSIONS: These
      results highlight that sensory neurons of the Galphao-expressing vomeronasal
      subsystem, together with the receptors they express and the molecular cues they
      detect, control a wide range of fundamental mating and reproductive behaviors in
      female mice.

PMID- 24886579
TI  - Visual outcome of mega-dose intravenous corticosteroid treatment in non-arteritic
      anterior ischemic optic neuropathy - retrospective analysis.
AB  - BACKGROUND: To date, non arteritic anterior ischemic optic neuropathy (NAION) is
      still incurable. We wish to evaluate the effect of intravenous (IV)
      corticosteroids on the visual outcome of NAION patients. METHODS: Visual
      parameters were retrospectively compared between NAION patients treated with IV
      corticosteroids and untreated NAION patients (control). Visual acuity (VA) and
      Humphrey automated static perimetry visual field (VF) defects of the affected eye
      were compared between groups at baseline, 1, 3, 6 months, and end of follow-up
      visits. The VF analysis consisted of number of quadrant involvements and mean
      deviation (MD). RESULTS: Each group comprised 23 patients (24 eyes). Mean initial
      VA was similar in the control and treatment groups (p = 0.8). VA at end of follow
      up did not improve in either groups (p = 0.8 treated group, p = 0.1 control
      group). No improvement and no difference in VF defects were found by either
      quadrant analysis (p = 0.1 treated group, p = 0.5 control group) or MD analysis
      (p = 0.2, treated group, p = 0.9 control group). VA and VF parameters tended to
      be worse in the treated group, although without statistical significance.
      CONCLUSIONS: Our results suggest that IV corticosteroids may not improve the
      visual outcome of NAION patients. Since intravenous corticosteroids could
      potentially cause serious adverse effects, this treatment for NAION is
      questionable.

PMID- 24886580
TI  - Decomposition of the drivers of the U.S. hospital spending growth, 2001-2009.
AB  - BACKGROUND: United States health care spending rose rapidly in the 2000s, after a
      period of temporary slowdown in the 1990s. However, the description of the
      overall trend and the understanding of the underlying drivers of this trend are
      very limited. This study investigates how well historical hospital cost/revenue
      drivers explain the recent hospital spending trend in the 2000s, and how
      important each of these drivers is. METHODS: We used aggregated time series data
      to describe the trend in total hospital spending, price, and quantity between
      2001 and 2009. We used the Oaxaca-Blinder method to investigate the relative
      importance of major hospital cost/spending drivers (derived from the literature)
      in explaining the change in hospital spending patterns between 2001 and 2007. We
      assembled data from Medicare Cost Reports, American Hospital Association annual
      surveys, Prospective Payment System (PPS) Impact Files, Medicare Provider
      Analysis and Review (MedPAR) Medicare claims data, InterStudy reports, National
      Health Expenditure data, and Area Resource Files. RESULTS: Aggregated time series
      trends show that high hospital spending between 2001 and 2009 appears to be
      driven by higher payment per unit of hospital output, not by increased
      utilization. Results using the Oaxaca-Blinder regression decomposition method
      indicate that changes in historically important spending drivers explain a
      limited 30% of unit-payment growth, but a higher 60% of utilization growth.
      Hospital staffing and labor-related costs, casemix, and demographics are the most
      important drivers of higher hospital revenue, utilization, and unit-payment.
      Technology is associated with lower utilization, higher unit payment, and limited
      increases in total revenue. Market competition, primarily because of increased
      managed care concentration, moderates total revenue growth by driving lower unit
      payment. CONCLUSIONS: Much of the rapidly rising hospital spending growth in the
      2000s in the United States is driven by factors not commonly known or well
      measured. Future studies need to explore new factors and dynamics that drive
      longer-term hospital spending growth in recent years, particularly through the
      channel of higher prices.

PMID- 24886582
TI  - An integrated approach in a case of facioscapulohumeral dystrophy.
AB  - BACKGROUND: Muscle fatigue, weakness and atrophy are basilar clinical features
      that accompany facioscapulohumeral dystrophy (FSHD) the third most common
      muscular dystrophy.No therapy is available for FSHD. CASE PRESENTATION: We
      describe the effects of 6mo exercise therapy and nutritional supplementation in a
      43-year-old woman severely affected by FSHD. CONCLUSION: A mixed exercise program
      combined with nutritional supplementation can be safely used with beneficial
      effects in selected patients with FSHD.

PMID- 24886581
TI  - Early specific cognitive-behavioural psychotherapy in subjects at high risk for
      bipolar disorders: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Bipolar disorders (BD) are among the most severe mental disorders
      with first clinical signs and symptoms frequently appearing in adolescence and
      early adulthood. The long latency in clinical diagnosis (and subsequent adequate
      treatment) adversely affects the course of disease, effectiveness of
      interventions and health-related quality of life, and increases the economic
      burden of BD. Despite uncertainties about risk constellations and symptomatology
      in the early stages of potentially developing BD, many adolescents and young
      adults seek help, and most of them suffer substantially from symptoms already
      leading to impairments in psychosocial functioning in school, training, at work
      and in their social relationships. We aimed to identify subjects at risk of
      developing BD and investigate the efficacy and safety of early specific cognitive
      behavioural psychotherapy (CBT) in this subpopulation. METHODS/DESIGN: EarlyCBT
      is a randomised controlled multi-centre clinical trial to evaluate the efficacy
      and safety of early specific CBT, including stress management and problem solving
      strategies, with elements of mindfulness-based therapy (MBT) versus unstructured
      group meetings for 14 weeks each and follow-up until week 78. Participants are
      recruited at seven university hospitals throughout Germany, which provide in- and
      outpatient care (including early recognition centres) for psychiatric patients.
      Subjects at high risk must be 15 to 30 years old and meet the combination of
      specified affective symptomatology, reduction of psychosocial functioning, and
      family history for (schizo)affective disorders. Primary efficacy endpoints are
      differences in psychosocial functioning and defined affective symptomatology at
      14 weeks between groups. Secondary endpoints include the above mentioned
      endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to
      baseline; perception of, reaction to and coping with stress; and conversion to
      full BD. DISCUSSION: To our knowledge, this is the first study to evaluate early
      specific CBT in subjects at high risk for BD. Structured diagnostic interviews
      are used to map the risk status and development of disease. With our study, the
      level of evidence for the treatment of those young patients will be significantly
      raised. TRIAL REGISTRATION: WHO International Clinical Trials Platform (ICTRP),
      identifier: DRKS00000444, date of registration: 16 June 2010.

PMID- 24886583
TI  - Beyond health aid: would an international equalization scheme for universal
      health coverage serve the international collective interest?
AB  - It has been argued that the international community is moving 'beyond aid'.
      International co-financing in the international collective interest is expected
      to replace altruistically motivated foreign aid. The World Health Organization
      promotes 'universal health coverage' as the overarching health goal for the next
      phase of the Millennium Development Goals. In order to provide a basic level of
      health care coverage, at least some countries will need foreign aid for decades
      to come. If international co-financing of global public goods is replacing
      foreign aid, is universal health coverage a hopeless endeavor? Or would universal
      health coverage somehow serve the international collective interest?Using the
      Sustainable Development Solutions Network proposal to finance universal health
      coverage as a test case, we examined the hypothesis that national social policies
      face the threat of a 'race to the bottom' due to global economic integration and
      that this threat could be mitigated through international social protection
      policies that include international cross-subsidies - a kind of 'equalization' at
      the international level.The evidence for the race to the bottom theory is
      inconclusive. We seem to be witnessing a 'convergence to the middle'. However,
      the 'middle' where 'convergence' of national social policies is likely to occur
      may not be high enough to keep income inequality in check.The implementation of
      the international equalization scheme proposed by the Sustainable Development
      Solutions Network would allow to ensure universal health coverage at a cost of
      US$55 in low income countries-the minimum cost estimated by the World Health
      Organization. The domestic efforts expected from low and middle countries are far
      more substantial than the international co-financing efforts expected from high
      income countries. This would contribute to 'convergence' of national social
      policies at a higher level. We therefore submit that the proposed international
      equalization scheme should not be considered as foreign aid, but rather as an
      international collective effort to protect and promote national social policy in
      times of global economic integration: thus serving the international collective
      interest. 

PMID- 24886586
TI  - Air temperature suitability for Plasmodium falciparum malaria transmission in
      Africa 2000-2012: a high-resolution spatiotemporal prediction.
AB  - BACKGROUND: Temperature suitability for malaria transmission is a useful
      predictor variable for spatial models of malaria infection prevalence. Existing
      continental or global models, however, are synoptic in nature and so do not
      characterize inter-annual variability in seasonal patterns of temperature
      suitability, reducing their utility for predicting malaria risk. METHODS: A
      malaria Temperature Suitability Index (TSI) was created by first modeling minimum
      and maximum air temperature with an eight-day temporal resolution from gap-filled
      MODerate Resolution Imaging Spectroradiometer (MODIS) daytime and night-time Land
      Surface Temperature (LST) datasets. An improved version of an existing biological
      model for malaria temperature suitability was then applied to the resulting
      temperature information for a 13-year data series. The mechanism underlying this
      biological model is simulation of emergent mosquito cohorts on a two-hour time
      step and tracking of each cohort throughout its life to quantify the impact air
      temperature has on both mosquito survival and sporozoite development. RESULTS:
      The results of this research consist of 154 monthly raster surfaces that
      characterize spatiotemporal patterns in TSI across Africa from April 2000 through
      December 2012 at a 1 km spatial resolution. Generalized TSI patterns were as
      expected, with consistently high values in equatorial rain forests, seasonally
      variable values in tropical savannas (wet and dry) and montane areas, and low
      values in arid, subtropical regions. Comparisons with synoptic approaches
      demonstrated the additional information available within the dynamic TSI dataset
      that is lost in equivalent synoptic products derived from long-term monthly
      averages. CONCLUSIONS: The dynamic TSI dataset presented here provides a new
      product with far richer spatial and temporal information than any other presently
      available for Africa. As spatiotemporal malaria modeling endeavors evolve,
      dynamic predictor variables such as the malaria temperature suitability data
      developed here will be essential for the rational assessment of changing patterns
      of malaria risk.

PMID- 24886585
TI  - The associations between endothelial lipase 584C/T polymorphism and HDL-C level
      and coronary heart disease susceptibility: a meta-analysis.
AB  - BACKGROUND: Studies had investigated the relationships between endothelial lipase
      (EL) 584C/T polymorphism and high density lipoprotein cholesterol (HDL-C) level
      and coronary heart disease (CHD), but the results were controversial. To
      investigate a more authentic associations between EL 584C/T polymorphism and HDL
      C level, and the risk of CHD, we performed this meta-analysis. METHODS: We
      searched electric databases for all articles on the associations between EL
      584C/T polymorphism and HDL-C level, and CHD risk. Odds ratios (ORs) with 95%
      confidence interval (CI) were used to evaluate the strength of the association
      between the EL 584C/T polymorphism and the CHD susceptibility. The pooled
      standardized mean difference (SMD) with 95% CI was used for the meta-analysis of
      EL 584C/T polymorphism and HDL-C level. Begg's funnel plots and Egger's test were
      used to examine the publication bias. RESULTS: For CHD association, the pooled OR
      was 0.829 (95% CI: 0.701-0.980, P = 0.028) for the dominant model and 0.882 (95%
      CI: 0.779-0.999, P = 0.049) for the allelic model. By meta-regression analysis,
      we found that only total sample size could influence the initial heterogeneity.
      When the subgroup analysis was carried out, we found that the protective effect
      only existed in the subgroups of relatively small sample size. Sensitivity
      analyses indicated that Tang's study influenced the overall results
      significantly. We calculated the pooled ORs again after excluding Tang's study
      and found the association between EL 584C/T polymorphism and the risk of CHD was
      not significant for any genetic model. For HDL-C level association, the carriers
      of 584 T allele had a higher HDL-C level than the non-carriers. The pooled SMD
      was 0.399 (95% CI: 0.094-0.704, P = 0.010). When the studies were stratified by
      ethnicity and total sample size, the positive effects existed in the Caucasians
      and in subgroups of larger sample size. No significant publication bias was found
      in the present meta-analysis. CONCLUSIONS: The results of the present meta
      analysis suggest that the carriers of EL 584 T allele have a higher HDL-C level
      in Caucasian populations. Whereas, it might not be a protective factor for CHD.

PMID- 24886587
TI  - Distributional potential of the Triatoma brasiliensis species complex at present
      and under scenarios of future climate conditions.
AB  - BACKGROUND: The Triatoma brasiliensis complex is a monophyletic group, comprising
      three species, one of which includes two subspecific taxa, distributed across 12
      Brazilian states, in the caatinga and cerrado biomes. Members of the complex are
      diverse in terms of epidemiological importance, morphology, biology, ecology, and
      genetics. Triatoma b. brasiliensis is the most disease-relevant member of the
      complex in terms of epidemiology, extensive distribution, broad feeding
      preferences, broad ecological distribution, and high rates of infection with
      Trypanosoma cruzi; consequently, it is considered the principal vector of Chagas
      disease in northeastern Brazil. METHODS: We used ecological niche models to
      estimate potential distributions of all members of the complex, and evaluated the
      potential for suitable adjacent areas to be colonized; we also present first
      evaluations of potential for climate change-mediated distributional shifts.
      Models were developed using the GARP and Maxent algorithms. RESULTS: Models for
      three members of the complex (T. b. brasiliensis, N = 332; T. b. macromelasoma, N
      = 35; and T. juazeirensis, N = 78) had significant distributional predictivity;
      however, models for T. sherlocki and T. melanica, both with very small sample
      sizes (N = 7), did not yield predictions that performed better than random. Model
      projections onto future-climate scenarios indicated little broad-scale potential
      for change in the potential distribution of the complex through 2050.
      CONCLUSIONS: This study suggests that T. b. brasiliensis is the member of the
      complex with the greatest distributional potential to colonize new areas:
      overall; however, the distribution of the complex appears relatively stable.
      These analyses offer key information to guide proactive monitoring and
      remediation activities to reduce risk of Chagas disease transmission.

PMID- 24886588
TI  - Sulfur compounds block MCP-1 production by Mycoplasma fermentans-infected
      macrophages through NF-kappaB inhibition.
AB  - BACKGROUND AND AIMS: Hydrogen sulfide (H2S), together with nitric oxide (NO) and
      carbon monoxide (CO), belongs to a family of endogenous signaling mediators
      termed "gasotransmitters". Recent studies suggest that H2S modulates many
      cellular processes and it has been recognized to play a central role in
      inflammation, in the cardiovascular and nervous systems. By infecting
      monocytes/macrophages with Mycoplasma fermentans (M.F.), a well-known pro
      inflammatory agent, we evaluated the effects of H2S. METHODS: M.F.-infected cells
      were analyzed by ELISA and real time RT-PCR to detect the M.F. effects on MCP-1
      and on MMP-12 expression. The role of two different H2S donors (NaHS and GYY4137)
      on MF-infected cells was determined by treating infected cells with H2S and then
      testing the culture supernatants for MCP-1 and on MMP-12 production by ELISA
      assay. In order to identify the pathway/s mediating H2S- anti-inflammatory
      activity, cells were also treated with specific pharmaceutical inhibitors.
      Cytoplasmic and nuclear accumulation of NF-kappaB heterodimers was analyzed.
      RESULTS: We show that H2S was able to reduce the production of pro-inflammatory
      cytokine MCP-1, that was induced in monocytes/macrophages during M.F. infection.
      Moreover, MCP-1 was induced by M.F. through Toll-like receptor (TLR)-mediated
      nuclear factor-kappaB (NF-kappaB) activation, as demonstrated by the fact that
      TLR inhibitors TIRAP and MyD88 and NF-kappaB inhibitor IKK were able to block the
      cytokine production. In contrast H2S treatment of M.F. infected macrophages
      reduced nuclear accumulation of NF-kappaB heterodimer p65/p52. CONCLUSIONS: Our
      data demonstrate that under the present conditions H2S is effective in reducing
      Mycoplasma-induced inflammation by targeting the NF-kappaB pathway. This supports
      further studies for possible clinical applications.

PMID- 24886589
TI  - Canine infection with Dirofilaria immitis, Borrelia burgdorferi, Anaplasma spp.,
      and Ehrlichia spp. in the United States, 2010-2012.
AB  - BACKGROUND: The geographic distribution of canine infection with vector-borne
      disease agents in the United States appears to be expanding. METHODS: To provide
      an updated assessment of geographic trends in canine infection with Dirofilaria
      immitis, Borrelia burgdorferi, Ehrlichia spp., and Anaplasma spp., we evaluated
      results from an average of 3,588,477 dogs tested annually by veterinarians
      throughout the United States from 2010 - 2012. RESULTS: As in an earlier summary
      report, the percent positive test results varied by agent and region, with
      antigen of D. immitis and antibody to Ehrlichia spp. most commonly identified in
      the Southeast (2.9% and 3.2%, respectively) and antibody to both B. burgdorferi
      and Anaplasma spp. most commonly identified in the Northeast (13.3% and 7.1%,
      respectively) and upper Midwest (4.4% and 3.9%, respectively). Percent positive
      test results for D. immitis antigen were lower in every region considered,
      including in the Southeast, than previously reported. Percent positive test
      results for antibodies to B. burgdorferi and Ehrlichia spp. were higher
      nationally than previously reported, and, for antibodies to Anaplasma spp., were
      higher in the Northeast but lower in the Midwest and West, than in the initial
      report. Annual reports of human cases of Lyme disease, ehrlichiosis, and
      anaplasmosis were associated with percent positive canine test results by state
      for each respective tick-borne disease agent (R2=0.701, 0.457, and 0.314,
      respectively). Within endemic areas, percent positive test results for all three
      tick-borne agents demonstrated evidence of geographic expansion. CONCLUSIONS:
      Continued national monitoring of canine test results for vector-borne zoonotic
      agents is an important tool for accurately mapping the geographic distribution of
      these agents, and greatly aids our understanding of the veterinary and public
      health threats they pose.

PMID- 24886591
TI  - A bacteriocin gene cluster able to enhance plasmid maintenance in Lactococcus
      lactis.
AB  - BACKGROUND: Lactococcus lactis is widely used as a dairy starter and has been
      extensively studied. Based on the acquired knowledge on its physiology and
      metabolism, new applications have been envisaged and there is an increasing
      interest of using L. lactis as a cell factory. Plasmids constitute the main
      toolbox for L. lactis genetic engineering and most rely on antibiotic resistant
      markers for plasmid selection and maintenance. In this work, we have assessed the
      ability of the bacteriocin Lactococcin 972 (Lcn972) gene cluster to behave as a
      food-grade post-segregational killing system to stabilize recombinant plasmids in
      L. lactis in the absence of antibiotics. Lcn972 is a non-lantibiotic bacteriocin
      encoded by the 11-kbp plasmid pBL1 with a potent antimicrobial activity against
      Lactococcus. RESULTS: Attempts to clone the full lcn972 operon with its own
      promoter (P972), the structural gene lcn972 and the immunity genes orf2-orf3 in
      the unstable plasmid pIL252 failed and only plasmids with a mutated promoter were
      recovered. Alternatively, cloning under other constitutive promoters was
      approached and achieved, but bacteriocin production levels were lower than those
      provided by pBL1. Segregational stability studies revealed that the recombinant
      plasmids that yielded high bacteriocin titers were maintained for at least 200
      generations without antibiotic selection. In the case of expression vectors such
      as pTRL1, the Lcn972 gene cluster also contributed to plasmid maintenance without
      compromising the production of the fluorescent mCherry protein. Furthermore,
      unstable Lcn972 recombinant plasmids became integrated into the chromosome
      through the activity of insertion sequences, supporting the notion that Lcn972
      does apply a strong selective pressure against susceptible cells. Despite of it,
      the Lcn972 gene cluster was not enough to avoid the use of antibiotics to select
      plasmid-bearing cells right after transformation. CONCLUSIONS: Inserting the
      Lcn972 cluster into segregational unstable plasmids prevents their lost by
      segregation and probable could be applied as an alternative to the use of
      antibiotics to support safer and more sustainable biotechnological applications
      of genetically engineered L. lactis.

PMID- 24886590
TI  - Detection of differential fetal and adult expression of chloride intracellular
      channel 4 (CLIC4) protein by analysis of a green fluorescent protein knock-in
      mouse line.
AB  - BACKGROUND: Chloride Intracellular Channel 4 (CLIC4) is one of seven members in
      the closely related CLIC protein family. CLIC4 is involved in multiple cellular
      processes including apoptosis, cellular differentiation, inflammation and
      endothelial tubulogenesis. Despite over a decade of research, no comprehensive in
      situ expression analysis of CLIC4 in a living organism has been reported. In
      order to fulfill this goal, we generated a knock-in mouse to express Green
      Fluorescent Protein (GFP) from the CLIC4 locus, thus substituting the GFP coding
      region for CLIC4. We used GFP protein expression to eliminate cross reaction with
      other CLIC family members. RESULTS: We analyzed CLIC4 expression during embryonic
      development and adult organs. During mid and late gestation, CLIC4 expression is
      modulated particularly in fetal brain, heart, thymus, liver and kidney as well as
      in developing brown adipose tissue and stratifying epidermis. In the adult mouse,
      CLIC4 is highly expressed globally in vascular endothelial cells as well as in
      liver, lung alveolar septae, pancreatic acini, spermatogonia, renal proximal
      tubules, cardiomyocytes and thymic epithelial cells. Neural expression included
      axonal tracks, olfactory bulb, Purkinje cell layer and dentate gyrus. Renal CLIC4
      expression was most pronounced in proximal tubules, although altered renal
      function was not detected in the absence of CLIC4. Myeloid cells and B cells of
      the spleen are rich in CLIC4 expression as are CD4 and CD8 positive T cells.
      CONCLUSIONS: In a comprehensive study detailing CLIC4 expression in situ in a
      mouse model that excludes cross reaction with other family members, we were able
      to document previously unreported expression for CLIC4 in developing fetus,
      particularly the brain. In addition, compartmentalized expression of CLIC4 in
      specific adult tissues and cells provides a focus to explore potential functions
      of this protein not addressed previously.

PMID- 24886592
TI  - Symptomatic hyponatremia following lateral medullary infarction: a case report.
AB  - BACKGROUND: Hyponatremia has been reported from patients with severe neurological
      disease, and the syndrome of inappropriate secretion of antidiuretic hormone and
      cerebral salt wasting syndrome are the two main etiologies of hyponatremia after
      brain injury. Here we describe a patient with a lateral medullary infarction who
      experienced symptomatic hyponatremia with finding suggestive of syndrome of
      inappropriate secretion of antidiuretic hormone followed by cerebral salt wasting
      syndrome. CASE PRESENTATION: A 70-year-old Korean man visited emergency room
      complaining of sudden onset vertigo and gait disturbance. Neurological exam
      showed left side ataxia, Horner syndrome, and right side hypesthesia. Brain
      magnetic resonance imaging disclosed acute infarction involving left lateral
      medulla. His neurological status was stabilized, but he began to complain of non
      vertiginous dizziness and general weakness five days after admission. Serum
      sodium level dropped from 131 mEq/mL to 122 mEq/mL with reduced serum osmolarity
      of 265 mOsm/L. The diagnosis of syndrome of inappropriate secretion of
      antidiuretic hormone was made and we restricted fluid intake, but his symptoms
      worsened and his mental status became drowsy. Follow up serum sodium level was
      108 mEq/L with volume loss, suggesting cerebral salt wasting syndrome. We treated
      him with hypertonic saline and his consciousness was recovered. CONCLUSION: This
      case shows symptomatic hyponatremia after lateral medullary infarction, providing
      insight about distinct pathogenesis of syndrome of inappropriate secretion of
      antidiuretic hormone and cerebral salt wasting syndrome.

PMID- 24886593
TI  - Correlation between pedometer and the Global Physical Activity Questionnaire on
      physical activity measurement in office workers.
AB  - BACKGROUND: This study aimed to examine the correlation of physical activity
      levels assessed by pedometer and those by the Global Physical Activity
      Questionnaire (GPAQ) in a population of office workers. METHODS: A cross
      sectional study was conducted on 320 office workers. A self-administered
      questionnaire was distributed to each office worker by hand. Physical activity
      level was objectively assessed by a pedometer for 7 consecutive days and
      subjectively assessed by the GPAQ. Based on the pedometer and GPAQ outcomes,
      participants were classified into 3 groups: inactive, moderately active, and
      highly active. RESULTS: No correlation in the physical activity level assessed by
      the pedometer and GPAQ was found (rs = .08, P = 0.15). When considering the
      pedometer as the criterion for comparison, 65.3% of participants had
      underestimated their physical activity level using the GPAQ, whereas 9.3% of
      participants overestimated their physical activity level. CONCLUSIONS: Physical
      activity level in office workers assessed by a subjective measure was greatly
      different from assessed by an objective tool. Consequently, research on physical
      activity level, especially in those with sedentary lifestyle, should consider
      using an objective measure to ensure that it closely reflects a person's physical
      activity level.

PMID- 24886594
TI  - Congenital coronary artery fistulae: a rare cause of heart failure in adults.
AB  - Coronary artery fistulae are uncommon, reported in 0.25% of patients undergoing
      coronary angiography. Two patients with congenital coronary artery fistula and
      coronary artery disease who presented with symptoms of exacerbated congestive
      heart failure out of proportion to their atherosclerotic burden were successfully
      treated by epicardial fistula ligation and coronary artery bypass grafting with
      marked improvement in functional status. 

PMID- 24886595
TI  - Implementing tobacco dependence treatment during clinical consultations: a
      qualitative study of clinicians' experiences, perceptions and behaviours in a
      South African primary health care setting.
AB  - BACKGROUND: Evidence suggests that healthcare providers (HCPs) in South Africa do
      not consistently offer tobacco dependence treatment (TDT) during clinical
      consultations. In order to understand and explain this behaviour in a South
      African context, we conducted a qualitative exploration of HCPs' experiences,
      perceptions and behaviours regarding TDT. METHODS: Individual qualitative
      interviews were conducted with physicians and nurses who were purposively
      selected. Themes were identified from interview transcripts using content
      analysis. Findings were triangulated and peer-reviewed, and were also verified by
      the participants. RESULTS: Fifteen physicians and four nurses were interviewed,
      none of whom used tobacco. These participants perceived TDT as an important task,
      but could not consistently implement it during clinical consultations due to
      health systems constraints (time-constraints because of patient-overload, the
      unavailability of cessation medications and a lack of support for referrals),
      misperceptions and misconceptions (negative outcome expectations about the
      effectiveness and feasibility of TDT), socio-cultural barriers (counselling older
      persons was perceived as challenging) and personal limitations (perceived low
      self-efficacy, poor knowledge and skills on implementing any evidence-based TDT
      framework). Patients are therefore selectively screened based on clinical
      relevance and offered only prescriptive brief advice. Participants recommended
      several systems changes, including academic detailing of tobacco status, training
      HCPs and incorporating tobacco cessation medications in the Essential Drug List.
      CONCLUSION: The reported selective screening and limited TDT interventions
      offered by HCPs are related to interactions between health systems constraints,
      personal limitations, and misperceptions and misconceptions about the
      effectiveness and feasibility of TDT during clinical consultation. Implementing
      the recommended systems changes has the potential to improve the implementation
      of TDT in South African primary health care (PHC).

PMID- 24886597
TI  - Fully customized placement of orthodontic miniplates: a novel clinical technique.
AB  - INTRODUCTION: The initial stability and survival rate of orthodontic mini
      implants are highly dependent on the amount of cortical bone at their insertion
      site. In areas with limited bone availability, mini-plates are preferred to
      provide effective skeletal anchorage. The purpose of this paper was to present a
      new clinical technique for the insertion of mini-plates. METHODS: In order to
      apply this new technique, a cone-beam image of the insertion area is required. A
      software (Galaxy Sirona, Bensheim, Germany) is used to construct a three
      dimensional image of the scanned area and to virtually determine the exact
      location of the mini-plate as well as the position of the fixation screws. A
      stereolithographic model (STL) is then created by means of a three-dimensional
      scanner.Prior to its surgical insertion, the bone plate is adapted to the stereo
      lithographic model. Finally, a custom transfer jig is fabricated in order to
      assist with accurate placement of the mini-plate intra-operatively. RESULTS: The
      presented technique minimizes intra-operative decision making, because the final
      position of the bone plate is determined pre-surgically. This significantly
      reduces the duration of the surgical procedure and improves its outcome.
      CONCLUSIONS: A novel method for surgical placement of orthodontic mini-plates is
      presented. The technique facilitates accurate adaptation of mini-plates and
      insertion of retaining surgical screws; thereby enabling clinicians to more
      confidently increase the use of bone plates, especially in anatomical areas where
      the success of non-osseointegrated mini-screws is less favorable.

PMID- 24886596
TI  - Artemin growth factor increases nicotinic cholinergic receptor subunit expression
      and activity in nociceptive sensory neurons.
AB  - BACKGROUND: Artemin (Artn), a member of the glial cell line-derived growth factor
      (GDNF) family, supports the development and function of a subpopulation of
      peptidergic, TRPV1-positive sensory neurons. Artn (enovin, neublastin) is
      elevated in inflamed tissue and its injection in skin causes transient thermal
      hyperalgesia. A genome wide expression analysis of trigeminal ganglia of mice
      that overexpress Artn in the skin (ART-OE mice) showed elevation in nicotinic
      acetylcholine receptor (nAChR) subunits, suggesting these ion channels contribute
      to Artn-induced sensitivity. Here we have used gene expression, immunolabeling,
      patch clamp electrophysiology and behavioral testing assays to investigate the
      link between Artn, nicotinic subunit expression and thermal hypersensitivity.
      RESULTS: Reverse transcriptase-PCR validation showed increased levels of mRNAs
      encoding the nAChR subunits alpha3 (13.3-fold), beta3 (4-fold) and beta4 (7.7
      fold) in trigeminal ganglia and alpha3 (4-fold) and beta4 (2.8-fold) in dorsal
      root ganglia (DRG) of ART-OE mice. Sensory ganglia of ART-OE mice had increased
      immunoreactivity for nAChRalpha3 and exhibited increased overlap in labeling with
      GFRalpha3-positive neurons. Patch clamp analysis of back-labeled cutaneous
      afferents showed that while the majority of nicotine-evoked currents in DRG
      neurons had biophysical and pharmacological properties of alpha7-subunit
      containing nAChRs, the Artn-induced increase in alpha3 and beta4 subunits
      resulted in functional channels. Behavioral analysis of ART-OE and wildtype mice
      showed that Artn-induced thermal hyperalgesia can be blocked by mecamylamine or
      hexamethonium. Complete Freund's adjuvant (CFA) inflammation of paw skin, which
      causes an increase in Artn in the skin, also increased the level of nAChR mRNAs
      in DRG. Finally, the increase in nAChRs transcription was not dependent on the
      Artn-induced increase in TRPV1 or TRPA1 in ART-OE mice since nAChRs were elevated
      in ganglia of TRPV1/TRPA1 double knockout mice. CONCLUSIONS: These findings
      suggest that Artn regulates the expression and composition of nAChRs in GFRalpha3
      nociceptors and that these changes contribute to the thermal hypersensitivity
      that develops in response to Artn injection and perhaps to inflammation.

PMID- 24886598
TI  - Comparison of the endocranial- and brain volumes in brachycephalic dogs,
      mesaticephalic dogs and Cavalier King Charles spaniels in relation to their body
      weight.
AB  - BACKGROUND: A number of studies have attempted to quantify the relative volumes
      of the endocranial volume and brain parenchyma in association with the
      pathogenesis of the Chiari-like malformation (CLM) in the Cavalier King Charles
      spaniel (CKCS). In our study we examine the influence of allometric scaling of
      the brain and cranial cavity volume on morphological parameters in different dog
      breeds. MRI scans of 110 dogs (35 mesaticephalic dogs, 35 brachycephalic dogs, 20
      CKCSs with SM, and 20 CKCSs without SM) have been used to create 3-dimensional
      volumetric models of skull and brain parts. Volumes were related to body weight
      calculating the adjusted means for different breeds. RESULTS: There was a strong
      global dependency of all volumes to body weight (P < 0.0001). The adjusted means
      of the absolute and relative volumes of brain parenchyma and cranial compartments
      are not significantly larger in CKCSs in comparison to brachycephalic and
      mesaticephalic dogs. A difference in absolute or relative volumes between CKCSs
      with and without SM after relating these values to body weight could not be
      identified. The relative volume of the hindbrain parenchyma (caudal fossa
      parenchyma percentage) was larger in brachycephalic dogs than in CKCSs, without
      causing herniation or SM. CONCLUSION: An influence of body weight exist in dogs,
      which can be sufficiently large to render conclusions on the difference in
      volumes of the brain and skull unsafe unless some account of the body weight is
      taken in the analysis. The results of this study challenge the role of
      overcrowding for the development of SM in dogs.

PMID- 24886599
TI  - Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal
      cancer cells.
AB  - BACKGROUND: The hypermethylation of Alcohol dehydrogenase iron containing 1
      (ADHFE1) was recently reported to be associated with colorectal cancer (CRC)
      differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC
      is still unclear. METHODS: The methylation status and expression levels of ADHFE1
      were investigated in primary tumor tissues and adjacent normal tissues of 73
      patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29,
      SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain
      reaction (QMSP) and real-time reverse transcription polymerase chain reaction
      (real time PCR), respectively. The effect of alcohol on the methylation status of
      ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real
      time PCR, immunoblot, and cell proliferation assay. RESULTS: ADHFE1 was
      hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues
      (p<0.05). The mRNA expression of ADHFE1 was significantly reduced in CRC compared
      to adjacent normal tissues (p<0.05) and its expression was decreased in the
      alcohol consumption group (p<0.05). ADHFE1 was hypermethylated and its expression
      was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol
      induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell
      proliferation of HT-29, SW480, and DLD-1cells. CONCLUSION: These results
      demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in
      CRC and alcohol induces methylation-mediated down expression of ADHFE1 and
      proliferation of CRC cells.

PMID- 24886600
TI  - A genetic variant in osteoprotegerin is associated with progression of joint
      destruction in rheumatoid arthritis.
AB  - INTRODUCTION: Progression of joint destruction in rheumatoid arthritis (RA) is
      partly heritably; 45 to 58% of the variance in joint destruction is estimated to
      be explained by genetic factors. The binding of RANKL (Receptor Activator for
      Nuclear Factor kappa B Ligand) to RANK results in the activation of TRAF6 (tumor
      necrosis factor (TNF) receptor associated factor-6), and osteoclast formation
      ultimately leading to enhanced bone resorption. This bone resorption is inhibited
      by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The
      OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling.
      Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6
      are associated with the rate of joint destruction in RA. METHODS: 1,418 patients
      with 4,885 X-rays of hands and feet derived from four independent data-sets were
      studied. In each data-set the relative increase of the progression rate per year
      in the presence of a genotype was assessed. First, explorative analyses were
      performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and
      TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly
      associated in phase-1 were genotyped in data-sets from Groningen (Netherlands),
      Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an
      inverse weighted variance meta-analysis. Bonferonni correction for multiple
      testing was applied. RESULTS: We found that 33 SNPs were significantly associated
      with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and
      four SNPs in RANK were associated with progression of joint destruction with P
      value <0.05. In the meta-analyses of all four data-sets, RA-patients with the
      minor allele of OPG-rs1485305 expressed higher rates of joint destruction
      compared to patients without these risk variants (P = 2.35x10-4). This variant
      was also significant after Bonferroni correction. CONCLUSIONS: These results
      indicate that a genetic variant in OPG is associated with a more severe rate of
      joint destruction in RA.

PMID- 24886602
TI  - An iterative tomosynthesis reconstruction using total variation combined with non
      local means filtering.
AB  - BACKGROUND: After the release of compressed sensing (CS) theory, reconstruction
      algorithms from sparse and incomplete data have shown great improvements in
      diminishing artifacts of missing data. Following this progress, both local and
      non-local regularization induced iterative reconstructions have been actively
      used in limited view angle imaging problems. METHODS: In this study, a 3D
      iterative image reconstruction method (ART + TV)NLM was introduced by combining
      local total variation (TV) with non-local means (NLM) filter. In the first step,
      TV minimization was applied to the image obtained by algebraic reconstruction
      technique (ART) for background noise removal with preserving edges. In the second
      step, NLM is used in order to suppress the out of focus slice blur which is the
      most existent image artifact in tomosynthesis imaging. NLM exploits the similar
      structures to increase the smoothness in the image reconstructed by ART + TV.
      RESULTS: A tomosynthesis system and a 3D phantom were designed to perform
      simulations to show the superior performance of our proposed (ART + TV)NLM over
      ART and widely used ART + TV methods. Visual inspections show a significant
      improvement in image quality compared to ART and ART + TV. CONCLUSIONS: RMSE,
      Structure SIMilarity (SSIM) value and SNR of a specific layer of interest (LOI)
      showed that by proper selection of NLM parameters, significant improvements can
      be achieved in terms of convergence rate and image quality.

PMID- 24886601
TI  - Tobacco BY-2 cell-free lysate: an alternative and highly-productive plant-based
      in vitro translation system.
AB  - BACKGROUND: Cell-free protein synthesis is a rapid and efficient method for the
      production of recombinant proteins. Usage of prokaryotic cell-free extracts often
      leads to non-functional proteins. Eukaryotic counterparts such as wheat germ
      extract (WGE) and rabbit reticulocyte lysate (RLL) may improve solubility and
      promote the correct folding of eukaryotic multi-domain proteins that are
      difficult to express in bacteria. However, the preparation of WGEs is complex and
      time-consuming, whereas RLLs suffer from low yields. Here we report the
      development of a novel cell-free system based on tobacco Bright Yellow 2 (BY-2)
      cells harvested in the exponential growth phase. RESULTS: The highly-productive
      BY-2 lysate (BYL) can be prepared quickly within 4-5 h, compared to 4-5 d for
      WGE. The efficiency of the BYL was tested using three model proteins: enhanced
      yellow fluorescent protein (eYFP) and two versions of luciferase. The added mRNA
      was optimized by testing different 5' and 3' untranslated regions (UTRs). The
      protein yield in batch and dialysis reactions using BYL was much higher than that
      of a commercial Promega WGE preparation, achieving a maximum yield of 80 MUg/mL
      of eYFP and 100 MUg/mL of luciferase, compared to only 45 MUg/mL of eYFP and 35
      MUg/mL of luciferase in WGEs. In dialysis reactions, the BYL yielded about 400
      MUg/mL eYFP, representing up to 50% more of the target protein than the Promega
      WGE, and equivalent to the amount using 5Prime WGE system. CONCLUSIONS: Due to
      the high yield and the short preparation time the BYL represents a remarkable
      improvement over current eukaryotic cell-free systems.

PMID- 24886603
TI  - Estrogenic chemicals often leach from BPA-free plastic products that are
      replacements for BPA-containing polycarbonate products.
AB  - BACKGROUND: Xenobiotic chemicals with estrogenic activity (EA), such as bisphenol
      A (BPA), have been reported to have potential adverse health effects in mammals,
      including humans, especially in fetal and infant stages. Concerns about safety
      have caused many manufacturers to use alternatives to polycarbonate (PC) resins
      to make hard and clear, reusable, plastic products that do not leach BPA.
      However, no study has focused on whether such BPA-free PC-replacement products,
      chosen for their perceived higher safety, especially for babies, also release
      other chemicals that have EA. METHODS: We used two, well-established, mammalian
      cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached
      into over 1000 saline or ethanol extracts of 50 unstressed or stressed
      (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An
      EA antagonist, ICI 182,780, was used to confirm that agonist activity in
      leachates was due to chemicals that activated the mammalian estrogen receptor.
      RESULTS: Many unstressed and stressed, PC-replacement-products made from acrylic,
      polystyrene, polyethersulfone, and TritanTM resins leached chemicals with EA,
      including products made for use by babies. Exposure to various forms of UV
      radiation often increased the leaching of chemicals with EA. In contrast, some
      BPA-free PC-replacement products made from glycol-modified polyethylene
      terephthalate or cyclic olefin polymer or co-polymer resins did not release
      chemicals with detectable EA under any conditions tested. CONCLUSIONS: This
      hazard assessment survey showed that many BPA-free PC- replacement products still
      leached chemicals having significant levels of EA, as did BPA-containing PC
      counterparts they were meant to replace. That is, BPA-free did not mean EA-free.
      However, this study also showed that some PC-replacement products did not leach
      chemicals having significant levels of EA. That is, EA-free PC-replacement
      products could be made in commercial quantities at prices that compete with PC
      replacement products that were not BPA-free. Since plastic products often have
      advantages (price, weight, shatter-resistance, etc.) compared to other materials
      such as steel or glass, it is not necessary to forgo those advantages to avoid
      release into foodstuffs or the environment of chemicals having EA that may have
      potential adverse effects on our health or the health of future generations.

PMID- 24886604
TI  - Identifying solutions to increase participation in physical activity
      interventions within a socio-economically disadvantaged community: a qualitative
      study.
AB  - BACKGROUND: There is an urgent need to increase population levels of physical
      activity, particularly amongst those who are socio-economically disadvantaged.
      Multiple factors influence physical activity behaviour but the generalisability
      of current evidence to such 'hard-to-reach' population subgroups is limited by
      difficulties in recruiting them into studies. Also, rigorous qualitative studies
      of lay perceptions and perceptions of community leaders about public health
      efforts to increase physical activity are sparse. We sought to explore, within a
      socio-economically disadvantaged community, residents' and community leaders'
      perceptions of physical activity (PA) interventions and issues regarding their
      implementation, in order to improve understanding of needs, expectations, and
      social/environmental factors relevant to future interventions. METHODS: Within an
      ongoing regeneration project (Connswater Community Greenway), in a socio
      economically disadvantaged community in Belfast, we collaborated with a Community
      Development Agency to purposively sample leaders from public- and voluntary
      sector community groups and residents. Individual semi-structured interviews were
      conducted with 12 leaders. Residents (n = 113), of both genders and a range of
      ages (14 to 86 years) participated in focus groups (n = 14) in local facilities.
      Interviews and focus groups were recorded, transcribed verbatim and analysed
      using a thematic framework. RESULTS: Three main themes were identified: awareness
      of PA interventions; factors contributing to intervention effectiveness; and
      barriers to participation in PA interventions. Participants reported awareness
      only of interventions in which they were involved directly, highlighting a need
      for better communications, both inter- and intra-sectoral, and with residents.
      Meaningful engagement of residents in planning/organisation, tailoring to local
      context, supporting volunteers, providing relevant resources and an 'exit
      strategy' were perceived as important factors related to intervention
      effectiveness. Negative attitudes such as apathy, disappointing experiences,
      information with no perceived personal relevance and limited access to facilities
      were barriers to people participating in interventions. CONCLUSIONS: These
      findings illustrate the complexity of influences on a community's participation
      in PA interventions and support a social-ecological approach to promoting PA.
      They highlight the need for cross-sector working, effective information exchange,
      involving residents in bottom-up planning and providing adequate financial and
      social support. An in-depth understanding of a target population's perspectives
      is of key importance in translating PA behaviour change theories into practice.

PMID- 24886605
TI  - Genetic modulation of the interleukin 6 (IL-6) system in patients with advanced
      gastric cancer: a background for an alternative target therapy.
AB  - BACKGROUND: IL-6 triggers oncogenic/angiogenic signals and the cytokine-dependent
      pro-cachexia cascade. The prognostic role of the functional IL-6 (promoter)
      rs1800795 and the IL-6R (receptor) rs8192284 single nucleotide polymorphisms
      (SNP) was studied in patients with advanced gastric cancer treated with
      palliative chemotherapy. METHODS: One-hundred-sixty-one patients were genotyped
      for rs1800795 and rs8192284 SNPs using polymerase chain reaction based
      restriction fragment length polymorphism (PCR-RFLP) analysis assay. These results
      were studied for association with overall survival (OS). RESULTS: In 161
      assessable patients, frequencies of rs1800795 G/G, G/C and C/C genotypes were
      46%, 42% and 12%, respectively. Frequencies of rs8192284 A/A, A/C and C/C
      genotypes were 36%, 45% and 19%, respectively. Carriers of the rs1800795 G/G and
      rs8192284 C/C genotypes showed the worst OS. In the multivariate model, rs1800795
      G/G (1.69 hazard ratio; 95% confidence interval 1.18-2.42), and rs8192284 C/C
      (1.78 hazard ratio; 95% confidence interval 1.12-2.83) confirmed an adverse
      prognostic impact. CONCLUSIONS: In this population, genetic variants that up
      regulate the IL-6 system showed impact on OS. This findings sustain the
      hypothesis that anti-IL-6 compounds deserve clinical studies as novel
      therapeutics in the palliative treatment of cancer patients.

PMID- 24886606
TI  - Improving Diabetes care through Examining, Advising, and prescribing (IDEA):
      protocol for a theory-based cluster randomised controlled trial of a multiple
      behaviour change intervention aimed at primary healthcare professionals.
AB  - BACKGROUND: New clinical research findings may require clinicians to change their
      behaviour to provide high-quality care to people with type 2 diabetes, likely
      requiring them to change multiple different clinical behaviours. The present
      study builds on findings from a UK-wide study of theory-based behavioural and
      organisational factors associated with prescribing, advising, and examining
      consistent with high-quality diabetes care. AIM: To develop and evaluate the
      effectiveness and cost of an intervention to improve multiple behaviours in
      clinicians involved in delivering high-quality care for type 2 diabetes.
      DESIGN/METHODS: We will conduct a two-armed cluster randomised controlled trial
      in 44 general practices in the North East of England to evaluate a theory-based
      behaviour change intervention. We will target improvement in six underperformed
      clinical behaviours highlighted in quality standards for type 2 diabetes:
      prescribing for hypertension; prescribing for glycaemic control; providing
      physical activity advice; providing nutrition advice; providing on-going
      education; and ensuring that feet have been examined. The primary outcome will be
      the proportion of patients appropriately prescribed and examined (using
      anonymised computer records), and advised (using anonymous patient surveys) at 12
      months. We will use behaviour change techniques targeting motivational,
      volitional, and impulsive factors that we have previously demonstrated to be
      predictive of multiple health professional behaviours involved in high-quality
      type 2 diabetes care. We will also investigate whether the intervention was
      delivered as designed (fidelity) by coding audiotaped workshops and
      interventionist delivery reports, and operated as hypothesised (process
      evaluation) by analysing responses to theory-based postal questionnaires. In
      addition, we will conduct post-trial qualitative interviews with practice teams
      to further inform the process evaluation, and a post-trial economic analysis to
      estimate the costs of the intervention and cost of service use. DISCUSSION:
      Consistent with UK Medical Research Council guidance and building on previous
      development research, this pragmatic cluster randomised trial will evaluate the
      effectiveness of a theory-based complex intervention focusing on changing
      multiple clinical behaviours to improve quality of diabetes care. TRIAL
      REGISTRATION: ISRCTN66498413.

PMID- 24886607
TI  - Knowledge and perceptions of hepatitis C infection and pesticides use in two
      rural villages in Egypt.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC), one of the most fatal types of
      malignancy, is increasing worldwide, and particularly in Egypt where there is a
      confluence of its contributing factors, including high prevalence of hepatitis C
      virus (HCV) infection, widespread use of pesticides, and diets that are
      contaminated by aflatoxin B1 (AFB1) in rural areas. We investigated knowledge,
      attitudes, and prevention practices related to HCV infection and pesticides use
      in rural Egypt, where over half of the population resides and agriculture is the
      predominant occupation. METHODS: From two rural villages we recruited 67
      residents aged 18-80 years, who completed a 40-item survey that included
      questions about demographics, knowledge of and protective measures relevant to
      pesticides use in the home and in agriculture, awareness and perceptions of HCV
      infection and its treatment and prevention. RESULTS: Among the 67 study
      participants, gender distribution was equal, the mean age was 47.2, and one third
      never attended school. More than 50% reported using pesticides at home, but fewer
      reported having some knowledge about its health effects. Twelve participants were
      agricultural workers, and 11 of them applied pesticides in the field and knew
      about their toxicity; however only one person was correctly using the appropriate
      protective equipment. Among all the participants, 52 did not know what causes HCV
      infection, and 42 of those who knew it was a virus mentioned incorrect modes of
      transmission; and 30 did not know the disease manifestations. CONCLUSION: In
      rural Egypt, there is a significant lack of knowledge of HCV infection and its
      transmission mode and limited use of protective measures against pesticides
      despite familiarity with these chemicals.

PMID- 24886608
TI  - Gene perturbation and intervention in context-sensitive stochastic Boolean
      networks.
AB  - BACKGROUND: In a gene regulatory network (GRN), gene expressions are affected by
      noise, and stochastic fluctuations exist in the interactions among genes. These
      stochastic interactions are context dependent, thus it becomes important to
      consider noise in a context-sensitive manner in a network model. As a logical
      model, context-sensitive probabilistic Boolean networks (CSPBNs) account for
      molecular and genetic noise in the temporal context of gene functions. In a CSPBN
      with n genes and k contexts, however, a computational complexity of O(nk222n) (or
      O(nk2n)) is required for an accurate (or approximate) computation of the state
      transition matrix (STM) of the size (2n ? k) * (2n ? k) (or 2n * 2n). The
      evaluation of a steady state distribution (SSD) is more challenging. Recently,
      stochastic Boolean networks (SBNs) have been proposed as an efficient
      implementation of an instantaneous PBN. RESULTS: The notion of stochastic Boolean
      networks (SBNs) is extended for the general model of PBNs, i.e., CSPBNs. This
      yields a novel structure of context-sensitive SBNs (CSSBNs) for modeling the
      stochasticity in a GRN. A CSSBN enables an efficient simulation of a CSPBN with a
      complexity of O(nLk2n) for computing the state transition matrix, where L is a
      factor related to the required sequence length in CSSBN for achieving a desired
      accuracy. A time-frame expanded CSSBN can further efficiently simulate the
      stationary behavior of a CSPBN and allow for a tunable tradeoff between accuracy
      and efficiency. The CSSBN approach is more efficient than an analytical method
      and more accurate than an approximate analysis. CONCLUSIONS: Context-sensitive
      stochastic Boolean networks (CSSBNs) are proposed as an efficient approach to
      modeling the effects of gene perturbation and intervention in gene regulatory
      networks. A CSSBN analysis provides biologically meaningful insights into the
      oscillatory dynamics of the p53-Mdm2 network in a context-switching environment.
      It is shown that random gene perturbation has a greater effect on the final
      distribution of the steady state of a network compared to context switching
      activities. The CSSBN approach can further predict the steady state distribution
      of a glioma network under gene intervention. Ultimately, this will help drug
      discovery and develop effective drug intervention strategies.

PMID- 24886610
TI  - Modulation of event-related desynchronization during kinematic and kinetic hand
      movements.
AB  - BACKGROUND: Event-related desynchronization/synchronization (ERD/ERS) is a
      relative power decrease/increase of electroencephalogram (EEG) in a specific
      frequency band during physical motor execution and mental motor imagery, thus it
      is widely used for the brain-computer interface (BCI) purpose. However what the
      ERD really reflects and its frequency band specific role have not been agreed and
      are under investigation. Understanding the underlying mechanism which causes a
      significant ERD would be crucial to improve the reliability of the ERD-based BCI.
      We systematically investigated the relationship between conditions of actual
      repetitive hand movements and resulting ERD. METHODS: Eleven healthy young
      participants were asked to close/open their right hand repetitively at three
      different speeds (Hold, 1/3 Hz, and 1 Hz) and four distinct motor loads (0, 2,
      10, and 15 kgf). In each condition, participants repeated 20 experimental trials,
      each of which consisted of rest (8-10 s), preparation (1 s) and task (6 s)
      periods. Under the Hold condition, participants were instructed to keep clenching
      their hand (i.e., isometric contraction) during the task period. Throughout the
      experiment, EEG signals were recorded from left and right motor areas for offline
      data analysis. We obtained time courses of EEG power spectrum to discuss the
      modulation of mu and beta-ERD/ERS due to the task conditions. RESULTS: We
      confirmed salient mu-ERD (8-13 Hz) and slightly weak beta-ERD (14-30 Hz) on both
      hemispheres during repetitive hand grasping movements. According to a 3 * 4 ANOVA
      (speed * motor load), both mu and beta-ERD during the task period were
      significantly weakened under the Hold condition, whereas no significant
      difference in the kinetics levels and interaction effect was observed.
      CONCLUSIONS: This study investigates the effect of changes in kinematics and
      kinetics on resulting ERD during repetitive hand grasping movements. The
      experimental results suggest that the strength of ERD may reflect the time
      differentiation of hand postures in motor planning process or the variation of
      proprioception resulting from hand movements, rather than the motor command
      generated in the down stream, which recruits a group of motor neurons.

PMID- 24886611
TI  - Hypomelanosis of Ito presenting with pediatric orthopedic issues: a case report.
AB  - INTRODUCTION: Hypomelanosis of Ito was originally described as a purely cutaneous
      disease. Extracutaneous manifestations were described later, forming a
      neurocutaneous syndrome including skeletal, muscular, ocular and central nervous
      system symptoms.Hypomelanosis of Ito is characterized by a depigmentation along
      the lines of Blaschko on the trunk and extremities in certain patterns.The aim of
      this article was to report another case and give an overview of the related
      orthopedic symptoms that have been previously described. It was also our wish to
      contribute with recommendations for consideration with regard to bandages on
      eczematous rashes, especially on clubfeet. CASE PRESENTATION: A one-and-a-half
      month-old boy of Caucasian background born with talipes equinovarus, or clubfoot,
      on his right foot presented with an eczematous rash after surgical correction and
      plaster bandaging. CONCLUSIONS: It is the appearance of hypopigmentation, either
      alone or in combination with a congenital malformation, particularly central
      nervous system or musculoskeletal anomalies, which should form the basis of a
      presumptive diagnosis. This should then lead to further investigations and should
      always include skin biopsies and a test for chromosomal mosaicism.We report the
      case of a boy with a clinical picture consisting of a depigmented skin pattern,
      mental retardation, pes cavus, talipes equinovarus, clinodactyly, eczema,
      inverted cilia of the eye, strabismus, reduced hearing, ventral hernia,
      glomerulonephritis, missing testicles, leg length discrepancy with scoliosis,
      back pain and a syrinx.It is perhaps impossible to make any conclusions about
      extracutaneous symptoms. However, some symptoms such as retardation, cramps and
      seizures, delayed development and hypotonia cannot be ignored.Because of the
      possibility of creating an undesirable and long postoperative period with
      complications, it is very important to have this diagnosis in mind when deciding
      to do surgery or not if there are signs of dermatological problems before
      surgery. In this case, it could also be good clinical practice to test the
      patient's reaction to plaster or other bandages.

PMID- 24886609
TI  - Roles of NFkappaB-miR-29s-MMP-2 circuitry in experimental choroidal
      neovascularization.
AB  - BACKGROUND: Previous reports have indicated that matrix metallopeptidase-2 (MMP
      2) regulates angiogenic processes, which are involved in choroidal
      neovascularization (CNV). However, the regulation of MMP-2 in CNV has not been
      well-characterized. To gain more information about the regulation of MMP-2 in
      CNV, we analyzed the circuitry associated with MMP-2 regulation in a CNV model
      and in cell cultures, focusing on NFkappaB and the microRNA-29 family (miR-29s).
      METHODS: The CNV model was established by subjecting C57BL/6 mice to fundus
      photocoagulation with a krypton red laser. In choroidal-retinal pigment
      epithelial (RPE) tissues of the model, immunohistochemistry was used to evaluate
      the angiogenesis and MMP-2 expression; reverse-transcription quantitative PCR (RT
      qPCR) was used to determine the levels of miR-29s; and western blot was used to
      analyze the protein levels of nuclear factor kappa-light-chain-enhancer of
      activated B cells (NFkappaB) inhibitor, IkappaBalpha, and its phosphorylated
      form, phospho-IkappaBalpha. At the cellular level, RT-qPCR was used to examine
      the levels of miR-29s following NFkappaB activation by tumor necrosis factor
      alpha (TNFalpha); and western blot and luciferase assay were used to determine
      the regulation of MMP-2 by miR-29s in a human RPE cell line (ARPE-19) and in an
      umbilical vein endothelial cell line (EA hy926). RESULTS: MMP-2 staining was
      increased in the choroidal neovascular membrane of laser-treated retina. Also,
      the NFkappaB pathway was induced in choroid-RPE tissue, as evidenced by a lower
      protein level of IkappaBalpha and a higher level of phospho-IkappaBalpha in the
      tissue homogenates than in those from non-treated eyes. During the period when
      the NFkappaB pathway was induced, reduced miR-29s were detected in the choroidal
      RPE tissue of the laser-treated eyes. In cultured ARPE-19 cells, TNFalpha
      decreased miR-29a, b, and c, and the effects were rescued by NFkappaB decoy. In
      ARPE-19 and EA hy926, miR-29s mimics reduced the contents of secreted MMP-2 in
      the culture media. We also documented that miR-29s reduced MMP-2 3'-UTR-mediated
      luciferase transcription. CONCLUSIONS: The results suggest that in CNV, NFkappaB
      activation inhibits miR-29s, which may contribute to angiogenesis by up
      regulating the MMP-2 protein level in RPE cells. These observations may help in
      developing a strategy for resolving CNV by targeting miR-29s levels.

PMID- 24886613
TI  - The glenohumeral joint - a mismatching system? A morphological analysis of the
      cartilaginous and osseous curvature of the humeral head and the glenoid cavity.
AB  - BACKGROUND: Radial mismatch, glenohumeral conformity ratios and differences
      between cartilaginous and osseous radii highly depend on the measured plane. The
      comparison of cartilaginous radii between humeral head and glenoid in different
      planes provides new information to understand the degree of conformity during
      abduction of the upper limb. METHODS: To investigate the radii, CT-images in soft
      tissue kernel of 9 specimen were analysed using an image visualization software.
      Statistical analysis of the obtained data was performed using the t-test.
      RESULTS: Measurements of the radii in the glenoid revealed a significantly larger
      radius for bone than cartilage, whereas for the humeral head the opposite was the
      case. Highest ratios for cartilage in the transverse plane were found in the
      inferior and central areas of the joint surface, whereas the smallest ratios were
      found in the superior area. The radial mismatch varied between 0.1 mm and 13.6
      mm, depending on the measured plane. CONCLUSIONS: The results suggest that in
      abduction, the cartilaginous guidance of the humeral head decreases. This might
      permit the humeral head an anterior-posterior shifting as well as superior
      inferior translation. Surgical reconstruction of the normal glenohumeral
      relationships necessitates precise information about the glenohumeral morphology
      to ensure proper sizing and correct placement of prosthetic components and
      osteochondral allografts.

PMID- 24886612
TI  - Awareness of physical activity in healthy middle-aged adults: a cross-sectional
      study of associations with sociodemographic, biological, behavioural, and
      psychological factors.
AB  - BACKGROUND: Interventions to promote physical activity have had limited success.
      One reason may be that inactive adults are unaware that their level of physical
      activity is inadequate and do not perceive a need to change their behaviour. We
      aimed to assess awareness of physical activity, defined as the agreement between
      self-rated and objective physical activity, and to investigate associations with
      sociodemographic, biological, behavioural, and psychological factors. METHODS: We
      conducted an exploratory, cross-sectional analysis of awareness of physical
      activity using baseline data collected from 453 participants of the Feedback,
      Awareness and Behaviour study (Cambridgeshire, UK). Self-rated physical activity
      was measured dichotomously by asking participants if they believed they were
      achieving the recommended level of physical activity. Responses were compared to
      objective physical activity, measured using a combined accelerometer and heart
      rate monitor (Actiheart(r)). Four awareness groups were created: overestimators,
      realistic inactives, underestimators, and realistic actives. Logistic regression
      was used to assess associations between awareness group and potential correlates.
      RESULTS: The mean (standard deviation) age of participants was 47.0 (6.9) years,
      44.4% were male, and 65.1% were overweight (body mass index >= 25). Of the 258
      (57.0%) who were objectively classified as inactive, 130 (50.4%) misperceived
      their physical activity by incorrectly stating that they were meeting the
      guidelines (overestimators). In a multivariable logistic regression model
      adjusted for age and sex, those with a lower body mass index (Odds Ratio (OR) =
      0.95, 95% Confidence Interval (CI) = 0.90 to 1.00), higher physical activity
      energy expenditure (OR = 1.03, 95% CI = 1.00 to 1.06) and self-reported physical
      activity (OR = 1.13, 95% CI = 1.07 to 1.19), and lower intention to increase
      physical activity (OR = 0.69, 95% CI = 0.48 to 0.99) and response efficacy (OR =
      0.53, 95% CI = 0.31 to 0.91) were more likely to overestimate their physical
      activity. CONCLUSIONS: Overestimators have more favourable health characteristics
      than those who are realistic about their inactivity, and their psychological
      characteristics suggest that they are less likely to change their behaviour.
      Personalised feedback about physical activity may be an important first step to
      behaviour change.

PMID- 24886615
TI  - Protocol: systematic review and meta-analyses of birth outcomes for women who
      intend at the onset of labour to give birth at home compared to women of low
      obstetrical risk who intend to give birth in hospital.
AB  - BACKGROUND: There has been a renewed interest in the place of birth, including
      intended home birth, for low risk women. In the absence of adequately-sized
      randomised controlled trials, a recent Cochrane review recommended that a
      systematic review and meta-analysis, including observational studies, be
      undertaken to inform this topic. The objective of this review is to determine if
      women intending at the onset of labour to give birth at home are more or less
      likely to experience a foetal or neonatal loss compared to a cohort of women who
      are comparable to the home birth cohort on the absence of risk factors but who
      intend to give birth in a hospital setting. METHODS: We will search using Embase,
      MEDLINE, CINAHL, AMED and the Cochrane Library to find studies published since
      1990 that compare foetal, neonatal and maternal outcomes for women who intended
      at the onset of labour to give birth at home to a comparison cohort of low risk
      women who intended at the onset of labour to give birth in hospital. We will
      obtain pooled estimates of effect using Review Manager. Because of the likelihood
      of differences in outcomes in settings where home birth is integrated into the
      health care system, we will stratify our results according to jurisdictions that
      have a health care system that integrates home birth and those where home birth
      is provided outside the usual health care system. Since parity is known to be
      associated with birth outcomes, only studies that take parity into account will
      be included in the meta-analyses. We will provide results by parity to the extent
      possible. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered with
      PROSPERO at http://www.crd.york.ac.uk/Prospero/ (Registration number:
      CRD42013004046).

PMID- 24886614
TI  - The distribution and prognosis of anomalous coronary arteries identified by
      cardiovascular magnetic resonance: 15 year experience from two tertiary centres.
AB  - BACKGROUND: Aberrant coronary arteries represent a diverse group of congenital
      disorders. Post-mortem studies reveal a high risk of exercise-related sudden
      cardiac death in those with an anomalous coronary artery originating from the
      opposite sinus of Valsalva (ACAOS) with an inter-arterial course. There is little
      documentation of lifetime history and long-term follow-up of patients with
      coronary artery anomalies. METHODS: Patients with anomalous coronary arteries
      undergoing cardiovascular magnetic resonance over a 15-year period were
      identified and classified by anatomy and course. Medical records were reviewed
      for major adverse cardiovascular events (MACE). Revascularisation or myocardial
      infarction counted only if occurring in the distribution of the anomalous artery.
      RESULTS: Consecutive patients with coronary artery anomalies were retrospectively
      identified (n = 172). Median follow-up time was 4.3 years (IQR 2.5-7.8, maximum
      15.6). 116 patients had ACAOS of which 64 (55%) had an inter-arterial course
      (IAC) and 52 (45%) did not. During follow up 110 ACAOS patients were alive, 5
      died and 1 lost to follow-up.ACAOS patients experienced 58 MACE events (5
      cardiovascular deaths, 5 PCI, 24 CABG and 24 had myocardial infarction). 47 MACE
      events occurred in ACAOS with IAC and 11 in those without (p < 0.0001), the
      statistical difference driven by surgical revascularisation and myocardial
      infarction. CONCLUSIONS: In life, patients with an anomalous coronary artery
      originating from the opposite sinus of Valsalva taking an IAC have higher rates
      of both myocardial infarction and surgical revascularisation during long-term
      follow up, compared to those without IAC.

PMID- 24886616
TI  - Rapidly growing glandular papilloma associated with mucus production: a case
      report.
AB  - BACKGROUND: Pulmonary glandular papillomas are rare neoplasms, and their very
      slow or absent growth over time generally facilitates establishing the diagnosis.
      CASE PRESENTATION: In an 84-year-old woman who underwent surgery for sigmoid
      colon cancer, a growing solitary pulmonary nodule was identified on postoperative
      follow-up computed tomography. A computer tomography-guided needle biopsy was
      performed under suspicion that the nodule was malignant. The histopathological
      findings suggested a glandular papilloma. Right basilar segmentectomy was carried
      out, and the lesion was completely resected. Postoperative histopathological
      examination revealed a benign glandular papilloma accompanied by mucus retention
      in the surrounding alveolar region. CONCLUSIONS: A malignant neoplasm is usually
      suspected when a pulmonary tumor shows rapid growth. However, glandular
      papillomas associated with mucus retention also tend to grow in some cases, and
      should be included in the differential diagnosis.

PMID- 24886618
TI  - Epiphora in lung cancer patients receiving docetaxel: a case series.
AB  - BACKGROUND: Docetaxel is a key antineoplastic drug for treatment of non-small
      cell lung cancer. Ocular adverse events of docetaxel include epiphora (excess
      tearing) and conjunctivitis. Epiphora has been reported to be associated with
      canalicular and nasolacrimal duct stenosis, but it is not necessarily caused by
      lacrimal duct obstruction. CASE PRESENTATION: We encountered three Japanese non
      small cell lung cancer patients who developed epiphora after the administration
      of docetaxel-based chemotherapy. One patient with lacrimal puncta stenosis showed
      improvement with probing and irrigation. The other two patients resolved
      following cessation of docetaxel or administration of artificial tears.
      CONCLUSION: As epiphora can interfere with activities of daily life and
      negatively affect quality of life, it is important for thoracic oncologists to be
      aware of this adverse event.

PMID- 24886617
TI  - C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates
      breast cancer growth and metastasis by modulating the tumor microenvironment.
AB  - INTRODUCTION: Although C-X-C motif chemokine 12 (CXCL12) has been shown to bind
      to C-X-C chemokine receptor type 7 (CXCR7), the exact molecular mechanism
      regulations by CXCL12/CXCR7 axis in breast tumor growth and metastasis are not
      well understood. CXCR7 expression has been shown to be upregulated during
      pathological processes such as inflammation and cancer. METHODS: Breast cancer
      cell lines were genetically silenced or pharmacologically inhibited for CXCR7
      and/or its downstream target signal transducer and activator of transcription 3
      (STAT3). 4T1 or 4T1 downregulated for CXCR7 and 4T1.2 breast cancer cell lines
      were injected in mammary gland of BALB/c mice to form tumors, and the molecular
      pathways regulating tumor growth and metastasis were assessed. RESULTS: In this
      study, we observed that CXCL12 enhances CXCR7-mediated breast cancer migration.
      Furthermore, genetic silencing or pharmacologic inhibition of CXCR7 reduced
      breast tumor growth and metastasis. Further elucidation of mechanisms revealed
      that CXCR7 mediates tumor growth and metastasis by activating proinflammatory
      STAT3 signaling and angiogenic markers. Furthermore, enhanced breast
      tumorigenicity and invasiveness were associated with macrophage infiltration.
      CXCR7 recruits tumor-promoting macrophages (M2) to the tumor site through
      regulation of the macrophage colony-stimulating factor (M-CSF)/macrophage colony
      stimulating factor receptor (MCSF-R) signaling pathway. In addition, CXCR7
      regulated breast cancer metastasis by enhancing expression of metalloproteinases
      (MMP-9, MMP-2) and vascular cell-adhesion molecule-1 (VCAM-1). We also observed
      that CXCR7 is highly expressed in invasive ductal carcinoma (IDC) and metastatic
      breast tissue in human patient samples. In addition, high CXCR7 expression in
      tumors correlates with worse prognosis for both overall survival and lung
      metastasis-free survival in IDC patients. CONCLUSION: These observations reveal
      that CXCR7 enhances breast cancer growth and metastasis via a novel pathway by
      modulating the tumor microenvironment. These findings identify CXCR7-mediated
      STAT3 activation and modulation of the tumor microenvironment as novel regulation
      of breast cancer growth and metastasis. These studies indicate that new
      strategies using CXCR7 inhibitors could be developed for antimetastatic therapy.

PMID- 24886619
TI  - The effect of continuous passive motion and sling exercise training on clinical
      and functional outcomes following total knee arthroplasty: a randomized active
      controlled clinical study.
AB  - BACKGROUND: The parallel-group randomized active-controlled clinical study was
      conducted to compare the effectiveness of two in-hospital range of motion (ROM)
      exercise programs following total knee arthroplasty (TKA). Continuous passive
      motion (CPM) is frequently used to increase ROM and improve postoperative
      recovery despite little conclusive scientific evidence. In contrast, a new active
      sling-based ROM therapy requires the activation of the knee joint muscles and
      dynamic joint stabilization. It was hypothesized that higher demands on muscle
      strength and muscle coordination during sling exercise training (ST) might be
      advantageous for early recovery following TKA. METHODS: A total of 125 patients
      undergoing primary TKA were assessed for eligibility. Thirty-eight patients were
      randomly assigned to receive ST or CPM (control intervention) during hospital
      stay. Patients were assessed before TKA for baseline measurement (pretest), 1 day
      before discharge (posttest) and 3 months after TKA (follow-up). The passive knee
      flexion range of motion (pFL) was the primary outcome measure. Secondary outcome
      measures included active knee flexion range of motion, active and passive knee
      extension ROM, static postural control, physical activity, pain, length of
      hospital stay as well as clinical, functional and quality-of-life outcomes (SF
      36, HSS and WOMAC scores). Data were analyzed according to the intention-to-treat
      principle. Differences between the groups were tested for significance by the
      unpaired Student's t test or an analysis of covariance (ANCOVA) adjusted for
      baseline, weight, sex, age, pain and physical activity. RESULTS: A between-group
      difference could be determined at posttest. The pFL was significantly higher by
      6.0 degrees  (95% CI 0.9 to 11.2 degrees ; P = 0.022) in the ST group. No
      difference between groups in pFL was documented at follow-up. Furthermore, no
      significant differences could be observed for any secondary outcome measure at
      posttest and follow-up. CONCLUSIONS: ST seems to have a clinically relevant
      beneficial short-term effect on pFL compared to CPM. The results support the
      implementation of ST in rehabilitation programs following TKA. LEVEL OF EVIDENCE:
      Therapy, level 2b.

PMID- 24886620
TI  - Difference in cytokine production and cell cycle progression induced by Epstein
      Barr virus Lmp1 deletion variants in Kmh2, a Hodgkin lymphoma cell line.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is associated with 20-40% of Hodgkin's
      Lymphoma (HL) cases. EBV-encoded latent membrane protein 1 (LMP1) is a well-known
      oncogenic protein and two C-terminal deletion variants, del30-LMP1 and del69
      LMP1, have been described in animal models to be more tumorigenic than the wild
      type form. This work aims to detail the implication of LMP1 in the development of
      HL and to characterize the particular effects of these variants. METHODS: We
      established HL-derived cell lines stably transfected with the pRT-LMP1 vector
      coding for the EBNA1 gene and allowing expression of the different LMP1 variants
      under the control of a doxycyclin-inducible promoter. Communication between cells
      was assessed by measuring the expression of various pro-inflammatory cytokines by
      flow cytometry after intracellular LMP1 and cytokine double staining.
      Proliferative properties of LMP1 variants were also compared by studying the
      repartition of cells in the different phases of the cell cycle after EdU
      incorporation combined to LMP1 and DAPI staining. RESULTS: All LMP1 proteins
      induced the expression of several pro-inflammatory cytokines such as TNF-alpha,
      TNF-beta, IL-6, RANTES/CCL5 and IFN-gamma. However, the del30-LMP1 variant
      induced cytokine expression at a lower level than the other variants, especially
      IFN-gamma, while the del69-LMP1 variant stimulated greater cytokine expression.
      In addition, we measured that all LMP1 proteins greatly impacted the cell cycle
      progression, triggering a reduction in the number of cells in S-phase and an
      accumulation of cells in the G2/M phase compared to the HL-non induced cells.
      Interestingly, the del30-LMP1 variant reduced the number of cells in S-phase in a
      significantly greater manner and also increased the number of cells in the G0/G1
      phase of the cell cycle. CONCLUSION: Weak IFN-gamma expression and specific
      alteration of the cell cycle might be a way for del30-LMP1 infected cells to
      escape the immune anti-viral response and to promote the development of cancer.
      The differences observed between the LMP1 variants reflect their own oncogenic
      properties and eventually impact the development of HL.

PMID- 24886622
TI  - Cryopreservation and replantation of amputated rat hind limbs.
AB  - BACKGROUND: In spite of the relatively high success rate of limb replantation,
      many patients cannot undergo replantation surgery because the preservation time
      of an amputated limb is only about six hours. In addition, although
      allotransplantation of composite tissues is being performed more commonly with
      increasingly greater success rates, the shortage of donors limits the number of
      patients that can be treated. So the purpose of this study is to examine the
      feasibility of cryopreservation and replantation of limbs in a rat model.
      METHODS: Twelve five-month-old Sprague-Dawley rats were divided evenly into group
      A (above-knee amputation) and group B (Syme's amputation). One hind limb was
      amputated from each rat. The limbs were irrigated with cryoprotectant, cooled in
      a controlled manner to -140 degrees C, and placed in liquid nitrogen. Thawing and
      replantation were performed 14 days later. RESULTS: In group A, the limbs became
      swollen after restoration of blood flow resulting in blood vessel compression and
      all replantations failed. In group B, restoration of blood flow was noted in all
      limbs after replantation. In one case, the rat chewed the replanted limb and
      replantation failed. The other five rats were followed for three months with no
      abnormalities noted in the replanted limbs. CONCLUSIONS: Limbs with a minimal
      amount of muscle tissue can be successfully cryopreserved and replanted.

PMID- 24886621
TI  - The dipeptidyl peptidase-4 inhibitor saxagliptin improves function of circulating
      pro-angiogenic cells from type 2 diabetic patients.
AB  - BACKGROUND: Type 2 diabetes (T2D) is associated with reduction and dysfunction of
      circulating pro-angiogenic cells (PACs). DPP-4 inhibitors, a class of oral agents
      for T2D, might possess pleiotropic vasculoprotective activities. Herein, we
      tested whether DPP-4 inhibition with Saxagliptin affects the function of
      circulating PACs from T2D and healthy subjects. METHODS: PACs were isolated from
      T2D (n = 20) and healthy (n = 20) subjects. Gene expression, clonogenesis,
      proliferation, adhesion, migration and tubulisation were assessed in vitro by
      incubating PACs with or without Saxagliptin and SDF-1alpha. Stimulation of
      angiogenesis by circulating cells from T2D patients treated with Saxagliptin or
      other non-incretinergic drugs was assessed in vivo using animal models. RESULTS:
      Soluble DPP-4 activity was predominant over cellular activity and was
      successfully inhibited by Saxagliptin. At baseline, T2D compared to healthy PACs
      contained less acLDL(+)Lectin(+) cells, and showed altered expression of genes
      related to adhesion and cell cycle regulation. This was reflected by impaired
      adhesion and clonogenesis/proliferative response of T2D PACs. Saxagliptin + SDF
      1alpha improved adhesion and tube sustaining capacity of PACs from T2D patients.
      CD14+ PACs were more responsive to Saxagliptin than CD14- PACs. While Saxagliptin
      modestly reduced angiogenesis by mature endothelial cells, circulating PACs
      progeny cells from T2D patients on Saxagliptin treatment displayed higher growth
      factor-inducible in vivo angiogenetic activity, compared to cells from T2D
      patients on non-incretinergic regimen. CONCLUSIONS: Saxagliptin reverses PACs
      dysfunction associated with T2D in vitro and improves inducible angiogenesis by
      circulating cells in vivo. These data add knowledge to the potential pleiotropic
      cardiovascular effects of DPP-4 inhibition.

PMID- 24886623
TI  - Low plasma selenium concentrations in critically ill children: the interaction
      effect between inflammation and selenium deficiency.
AB  - INTRODUCTION: Low plasma selenium concentrations are frequent in critically ill
      patients. However, whether this is due to systemic inflammation, a deficient
      nutritional state or both is still not clear. We aimed to determine the factors
      associated with low plasma selenium in critically ill children while considering
      the inflammatory response and nutritional status. METHOD: A prospective study was
      conducted in 173 children (median age 34 months) with systemic inflammatory
      response who had plasma selenium concentrations assessed 48 hours after admission
      and on the 5th day of ICU stay. The normal reference range was 0.58 MUmol/L to
      1.6 MUmol/L. The outcome variable was 'low plasma selenium', which was defined as
      plasma selenium values below the distribution median during this period. The main
      explanatory variables were age, malnutrition, sepsis, C-reactive protein (CRP),
      and clinical severity scores. The data were analyzed using a Binomial Generalized
      Estimating Equations model, which includes the correlation between admission and
      5th day responses. RESULTS: Malnutrition and CRP were associated with low plasma
      selenium. The interaction effect between these two variables was significant.
      When CRP values were less than or equal to 40 mg/L, malnutrition was associated
      with low plasma selenium levels (odds ratio (OR) = 3.25, 95% confidence interval
      (CI) 1.39 to 7.63, P = 0.007; OR = 2.98, 95% CI 1.26 to 7.06, P = 0.013; OR =
      2.49, 95% CI 1.01 to 6.17, P = 0.049, for CRP = 10, 20 and 40 mg/L,
      respectively). This effect decreased as CRP concentrations increased and there
      was loose significance when CRP values were >40 mg/L. Similarly, the effect of
      CRP on low plasma selenium was significant for well-nourished patients (OR =
      1.13; 95% CI 1.06 to 1.22, P <0.001) but not for the malnourished (OR = 1.03; 95%
      CI 0.99 to 1.08, P = 0.16). CONCLUSIONS: There is a significant interaction
      between the magnitude of the inflammatory response and malnutrition on low plasma
      selenium. This interaction should be considered when interpreting plasma
      concentrations as an index of selenium status in patients with systemic
      inflammation as well as in the decision on selenium supplementation.

PMID- 24886624
TI  - CDK9 inhibition strategy defines distinct sets of target genes.
AB  - BACKGROUND: CDK9 is the catalytic subunit of the Positive Transcription
      Elongation Factor b (P-TEFb), which phosphorylates the CTD of RNAPII and negative
      elongation factors enabling for productive elongation after initiation. CDK9
      associates with T-type cyclins and cyclin K and its activity is tightly regulated
      in cells at different levels. CDK9 is also the catalytic subunit of TAK (Tat
      activating Kinase), essential for HIV1 replication. Because of CDK9's potential
      as a therapeutic target in AIDS, cancer, inflammation, and cardiomyophathy it is
      important to understand the consequences of CDK9 inhibition. A previous gene
      expression profiling study performed with human glioblastoma T98G cells in which
      CDK9 activity was inhibited either with a dominant negative mutant form of CDK9
      (dnCDK9) or the pharmacological inhibitor Flavopiridol unveiled striking
      differences in gene expression effects. In the present report we extended these
      studies by (1) using both immortalized normal human fibroblasts and primary human
      astrocytes, (2) eliminating potential experimental variability due to
      transduction methodology and (3) also modulating CDK9 activity with siRNA.
      FINDINGS: Striking differences in the effects on gene expression resulting from
      the strategy used to inhibit CDK9 activity (dnCDK9 or FVP) remain even when
      potential variability due to viral transduction is eliminated. siRNA mediated
      CDK9 knockdown in human fibroblasts and astrocytes efficiently reduced CDK9
      expression and led to potent changes in gene expression that exhibit little
      correlation with the effects of dnCDK9 or FVP. Interestingly, HEXIM1 a validated
      CDK9 target gene, was found to be potently downregulated by dnCDK9, FVP and
      siCDK9, but the cluster of genes with expression profiles similar to HEXIM1 was
      small. Finally, cluster analysis of all treatments revealed higher correlation
      between treatments than cell type origin. CONCLUSION: The nature of the strategy
      used to inhibit CDK9 profoundly affects the patterns of gene expression resulting
      from CDK9 inhibition. These results suggest multiple variables that affect
      outcome, including kinetics of inhibition, potency, off-target effects, and
      selectivity issues. This is particularly important when considering CDK9 as a
      potential target for therapeutic intervention.

PMID- 24886625
TI  - Calibration of self-report tools for physical activity research: the Physical
      Activity Questionnaire (PAQ).
AB  - BACKGROUND: The utility of self-report measures of physical activity (PA) in
      youth can be greatly enhanced by calibrating self-report output against
      objectively measured PA data.This study demonstrates the potential of calibrating
      self-report output against objectively measured physical activity (PA) in youth
      by using a commonly used self-report tool called the Physical Activity
      Questionnaire (PAQ). METHODS: A total of 148 participants (grades 4 through 12)
      from 9 schools (during the 2009-2010 school year) wore an Actigraph accelerometer
      for 7 days and then completed the PAQ. Multiple linear regression modeling was
      used on 70% of the available sample to develop a calibration equation and this
      was cross validated on an independent sample of participants (30% of sample).
      RESULTS: A calibration model with age, gender, and PAQ scores explained 40% of
      the variance in values for the percentage of time in moderate-to-vigorous PA
      (%MVPA) measured from the accelerometers (%MVPA = 14.56 - (sex*0.98) - (0.84*age)
      + (1.01*PAQ)). When tested on an independent, hold-out sample, the model
      estimated %MVPA values that were highly correlated with the recorded
      accelerometer values (r = .63) and there was no significant difference between
      the estimated and recorded activity values (mean diff. = 25.3 +/- 18.1 min; p =
      .17). CONCLUSIONS: These results suggest that the calibrated PAQ may be a valid
      alternative tool to activity monitoring instruments for estimating %MVPA in
      groups of youth.

PMID- 24886626
TI  - Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED
      Study.
AB  - BACKGROUND: It is unknown whether individuals at high cardiovascular risk sustain
      a benefit in cardiovascular disease from increased olive oil consumption. The aim
      was to assess the association between total olive oil intake, its varieties
      (extra virgin and common olive oil) and the risk of cardiovascular disease and
      mortality in a Mediterranean population at high cardiovascular risk. METHODS: We
      included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years,
      from the PREvencion con DIeta MEDiterranea (PREDIMED) study, a multicenter,
      randomized, controlled, clinical trial. Participants were randomized to one of
      three interventions: Mediterranean Diets supplemented with nuts or extra-virgin
      olive oil, or a control low-fat diet. The present analysis was conducted as an
      observational prospective cohort study. The median follow-up was 4.8 years.
      Cardiovascular disease (stroke, myocardial infarction and cardiovascular death)
      and mortality were ascertained by medical records and National Death Index. Olive
      oil consumption was evaluated with validated food frequency questionnaires.
      Multivariate Cox proportional hazards and generalized estimating equations were
      used to assess the association between baseline and yearly repeated measurements
      of olive oil intake, cardiovascular disease and mortality. RESULTS: During follow
      up, 277 cardiovascular events and 323 deaths occurred. Participants in the
      highest energy-adjusted tertile of baseline total olive oil and extra-virgin
      olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61;
      95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively,
      compared to the reference. Higher baseline total olive oil consumption was
      associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of
      cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil
      consumption, cardiovascular disease and mortality risk decreased by 10% and 7%,
      respectively. No significant associations were found for cancer and all-cause
      mortality. The associations between cardiovascular events and extra virgin olive
      oil intake were significant in the Mediterranean diet intervention groups and not
      in the control group. CONCLUSIONS: Olive oil consumption, specifically the extra
      virgin variety, is associated with reduced risks of cardiovascular disease and
      mortality in individuals at high cardiovascular risk. TRIAL REGISTRATION: This
      study was registered at controlled-trials.com (http://www.controlled
      trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial
      Number (ISRCTN): 35739639. Registration date: 5 October 2005.

PMID- 24886627
TI  - Using marketing theory to inform strategies for recruitment: a recruitment
      optimisation model and the txt2stop experience.
AB  - BACKGROUND: Recruitment is a major challenge for many trials; just over half
      reach their targets and almost a third resort to grant extensions. The economic
      and societal implications of this shortcoming are significant. Yet, we have a
      limited understanding of the processes that increase the probability that
      recruitment targets will be achieved. Accordingly, there is an urgent need to
      bring analytical rigour to the task of improving recruitment, thereby increasing
      the likelihood that trials reach their recruitment targets. This paper presents a
      conceptual framework that can be used to improve recruitment to clinical trials.
      METHODS: Using a case-study approach, we reviewed the range of initiatives that
      had been undertaken to improve recruitment in the txt2stop trial using
      qualitative (semi-structured interviews with the principal investigator) and
      quantitative (recruitment) data analysis. Later, the txt2stop recruitment
      practices were compared to a previous model of marketing a trial and to key
      constructs in social marketing theory. RESULTS: Post hoc, we developed a
      recruitment optimisation model to serve as a conceptual framework to improve
      recruitment to clinical trials. A core premise of the model is that improving
      recruitment needs to be an iterative, learning process. The model describes three
      essential activities: i) recruitment phase monitoring, ii) marketing research,
      and iii) the evaluation of current performance. We describe the initiatives
      undertaken by the txt2stop trial and the results achieved, as an example of the
      use of the model. CONCLUSIONS: Further research should explore the impact of
      adopting the recruitment optimisation model when applied to other trials.

PMID- 24886628
TI  - Chryseobacterium indologenes in a woman with acute leukemia in Senegal: a case
      report.
AB  - INTRODUCTION: This report documents a rare case of Chryseobacterium indologenes
      urinary tract infection in Senegal. Chryseobacterium indologenes is an uncommon
      human pathogen reported in hospital outbreaks in Taiwan and there have been some
      sporadic cases reported in Europe and in the USA mainly from immune-suppressed
      patients. CASE PRESENTATION: This case report describes a 42-year-old woman of
      Wolofa ethnicity who was hospitalized in our Department of Internal Medicine in a
      Senegalese university teaching hospital, with acute leukemia who died of severe
      sepsis 10 days following her hospitalization. A strain of Chryseobacterium
      indologenes isolated from her urine sample was resistant to several beta-lactams
      including ampicillin (minimum inhibitory concentrations >= 256 MUg/mL),
      cefotaxime (minimum inhibitory concentrations 32 MUg/mL) and imipenem (minimum
      inhibitory concentrations >= 32 MUg/mL), whereas it was susceptible to
      piperacillin (minimum inhibitory concentrations 16 MUg/mL), cefepime (minimum
      inhibitory concentrations 4 MUg/mL), ceftazidime (minimum inhibitory
      concentrations 4 MUg/mL), trimethoprim-sulfamethoxazole (minimum inhibitory
      concentrations <= 0.25 MUg/mL) and all tested quinolones including nalidixic acid
      (minimum inhibitory concentrations <= 2 MUg/mL). CONCLUSIONS: Chryseobacterium
      indologenes although uncommon, is an important pathogen causing infection in
      hospitalized patients. The management of this infection needs better
      identification, drug susceptibility testing and monitoring of immunosuppressed
      patients with long hospitalizations.

PMID- 24886629
TI  - American Cutaneous Leishmaniasis in Panama: a historical review of entomological
      studies on anthropophilic Lutzomyia sand fly species.
AB  - We review existing information on the epidemiology of American Cutaneous
      Leishmaniasis (ACL) in Panama, with emphasis on the bionomics of anthropophilic
      Lutzomyia sand fly species. Evidence from Panamanian studies suggests that there
      are six anthropophilic species in the country: Lutzomyia trapidoi, Lu.
      panamensis, Lu. gomezi, Lu. ylephiletor, Lu. sanguinaria and Lu. pessoana
      (Henceforth Lu. carrerai thula). In general, these taxa are abundant, widespread
      and feed opportunistically on their hosts, which make them potential transmitters
      of pathogens to a broad range of wildlife, domesticated animals and humans.
      Furthermore, nearly all man-biting species in Panama (with the exception of Lu.
      gomezi) expand demographically during the rainy season when transmission is
      likely higher due to elevated Leishmania infection rates in vector populations.
      Despite this, data on the distribution and prevalence of ACL suggest little
      influence of vector density on transmission intensity. Apart from Lu. trapidoi,
      anthropophilic species seem to be most active in the understory, but vertical
      stratification, as well as their opportunistic feeding behavior, could vary
      geographically. This in turn seems related to variation in host species
      composition and relative abundance across sites that have experienced different
      degrees of human alteration (e.g., deforestation) in leishmaniasis endemic
      regions of Panama. 

PMID- 24886630
TI  - Characterizing the effect of temperature fluctuation on the incidence of malaria:
      an epidemiological study in south-west China using the varying coefficient
      distributed lag non-linear model.
AB  - BACKGROUND: Malaria transmission is strongly determined by the environmental
      temperature and the environment is rarely constant. Therefore, mosquitoes and
      parasites are not only exposed to the mean temperature, but also to daily
      temperature variation. Recently, both theoretical and laboratory work has shown,
      in addition to mean temperatures, daily fluctuations in temperature can affect
      essential mosquito and parasite traits that determine malaria transmission
      intensity. However, so far there is no epidemiological evidence at the population
      level to this problem. METHODS: Thirty counties in southwest China were selected,
      and corresponding weekly malaria cases and weekly meteorological variables were
      collected from 2004 to 2009. Particularly, maximum, mean and minimum temperatures
      were collected. The daily temperature fluctuation was measured by the diurnal
      temperature range (DTR), the difference between the maximum and minimum
      temperature. The distributed lag non-linear model (MDLNM) was used to study the
      correlation between weekly malaria incidences and weekly mean temperatures, and
      the correlation pattern was allowed to vary over different levels of daily
      temperature fluctuations. RESULTS: The overall non-linear patterns for mean
      temperatures are distinct across different levels of DTR. When under cooler
      temperature conditions, the larger mean temperature effect on malaria incidences
      is found in the groups of higher DTR, suggesting that large daily temperature
      fluctuations act to speed up the malaria incidence in cooler environmental
      conditions. In contrast, high daily fluctuations under warmer conditions will
      lead to slow down the mean temperature effect. Furthermore, in the group of
      highest DTR, 24-25 degrees C or 21-23 degrees C are detected as the optimal
      temperature for the malaria transmission. CONCLUSION: The environment is rarely
      constant, and the result highlights the need to consider temperature fluctuations
      as well as mean temperatures, when trying to understand or predict malaria
      transmission. This work may be the first epidemiological study confirming that
      the effect of the mean temperature depends on temperature fluctuations, resulting
      in relevant evidence at the population level.

PMID- 24886631
TI  - Antibodies reacting with Simian Virus 40 capsid protein mimotopes in serum
      samples from patients affected by uveal melanoma.
AB  - The uveal melanoma (UM) is the most common human intraocular tumour. Simian Virus
      40 (SV-40) is a small DNA tumor virus detected in some malignancies, including
      the cutaneous melanoma. In this study an indirect ELISA using synthetic peptides
      that mimic SV-40 antigens, was employed to detect antibodies against SV-40 in
      serum samples from UM patients. Our report indicates a significant higher
      prevalence of antibodies against SV-40 capsid protein antigens in serum samples
      from UM patients compared to controls. Our data suggest an association between UM
      and SV-40, indicating that patients affected by uveal melanoma tested SV-40
      positive could be treated by innovative therapies. 

PMID- 24886632
TI  - Brain-blood amino acid correlates following protein restriction in murine maple
      syrup urine disease.
AB  - BACKGROUND: Conventional therapy for patients with maple syrup urine disease
      (MSUD) entails restriction of protein intake to maintain acceptable levels of the
      branched chain amino acid, leucine (LEU), monitored in blood. However, no data
      exists on the correlation between brain and blood LEU with protein restriction,
      and whether correction in blood is reflected in brain. METHODS: To address this
      question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein,
      with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for
      quantitative amino acid analyses. RESULTS: LEU and valine (VAL) levels in all
      brain regions improved on average 28% when shifting from 19% to 6% protein,
      whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in
      brain regions did not improve, while the SE level improved 24% with low-protein
      consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE))
      were 362-434 MUM, consistent with human values considered within control.
      Nonetheless, numerous amino acids in brain regions remained abnormal despite
      protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU),
      gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine
      (SER). To assess the specificity of these anomalies, we piloted preliminary
      studies in hyperphenylalaninemic mice, modeling another large neutral
      aminoacidopathy. Employing an identical dietary regimen, we found remarkably
      consistent abnormalities in GLN, ASP, and GLU. CONCLUSIONS: Our results suggest
      that blood amino acid analysis may be a poor surrogate for assessing the outcomes
      of protein restriction in the large neutral amino acidopathies, and further
      indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may
      contribute to long-term neurocognitive dysfunction in these disorders.

PMID- 24886633
TI  - Lentiviral and targeted cellular barcoding reveals ongoing clonal dynamics of
      cell lines in vitro and in vivo.
AB  - BACKGROUND: Cell lines are often regarded as clonal, even though this simplifies
      what is known about mutagenesis, transformation and other processes that
      destabilize them over time. Monitoring these clonal dynamics is important for
      multiple areas of biomedical research, including stem cell and cancer biology.
      Tracking the contributions of individual cells to large populations, however, has
      been constrained by limitations in sensitivity and complexity. RESULTS: We
      utilize cellular barcoding methods to simultaneously track the clonal
      contributions of tens of thousands of cells. We demonstrate that even with
      optimal culturing conditions, common cell lines including HeLa, K562 and HEK-293
      T exhibit ongoing clonal dynamics. Starting a population with a single clone
      diminishes but does not eradicate this phenomenon. Next, we compare lentiviral
      and zinc-finger nuclease barcode insertion approaches, finding that the zinc
      finger nuclease protocol surprisingly results in reduced clonal diversity. We
      also document the expected reduction in clonal complexity when cells are
      challenged with genotoxic stress. Finally, we demonstrate that xenografts
      maintain clonal diversity to a greater extent than in vitro culturing of the
      human non-small-cell lung cancer cell line HCC827. CONCLUSIONS: We demonstrate
      the feasibility of tracking and quantifying the clonal dynamics of entire cell
      populations within multiple cultured cell lines. Our results suggest that cell
      heterogeneity should be considered in the design and interpretation of in vitro
      culture experiments. Aside from clonal cell lines, we propose that cellular
      barcoding could prove valuable in modeling the clonal behavior of heterogeneous
      cell populations over time, including tumor populations treated with
      chemotherapeutic agents.

PMID- 24886634
TI  - Spontaneous antral follicle formation and metaphase II oocyte from a non
      stimulated prepubertal ovarian tissue xenotransplant.
AB  - BACKGROUND: Current strategies in cancer treatment have markedly increased the
      rates of remission and survival for cancer patients, but are often associated
      with subsequent sterility. While there are various options available to an adult
      female depending on the patient's particular situation, the only realistic option
      for preserving fertility in prepubertal females is to cryopreserve ovarian
      tissue. This is the first report of a morphologically mature oocyte collected
      from non-stimulated prepubertal ovarian tissue xenotransplants. METHODS: Ovarian
      tissue from a 6 year old patient suffering from nephroblastoma was removed and
      cryopreserved for fertility preservation. The frozen-thawed ovarian tissue
      fragments were xenotransplanted to bilaterally oophorectomized severe combined
      immunodeficiency (SCID) mice to assess follicle development. RESULTS: Antral
      follicle formation occurred post-xenotransplantation in a single ovarian fragment
      without exogenous hormone stimulation. A morphologically maturing oocyte was
      harvested from these follicles. CONCLUSIONS: Prepubertal human ovarian follicles
      and oocytes can be matured after xenotransplantation even without exogenous
      hormone stimulation. These results indicate that tissue collected from
      prepubertal patients can support fertility in cancer survivors.

PMID- 24886635
TI  - Comparative study of the effects of fetal bovine serum versus horse serum on
      growth and differentiation of primary equine bronchial fibroblasts.
AB  - BACKGROUND: Airway fibroblasts have become a critical addition to all facets of
      structural lung tissue changes such as in human asthma and chronic obstructive
      pulmonary disease, but little is known about their role in the equine recurrent
      airway obstruction, a disease that resembles to the human asthma. Since the
      equine bronchial fibroblasts (EBF) have not been isolated and characterized yet,
      the use of defined medium was investigated. RESULTS: Primary EBF were cultured on
      non-collagen coated flasks without serum or in the presence of fetal bovine serum
      (FBS) or horse serum (HS) or in serum depleted medium. EBF cultured in serum-free
      basal media and those serum deprived were not able to proliferate and even
      exhibited considerable cell death. In media containing FBS or HS, proliferation
      of the cells was reproducible between different primary cultures and cells
      demonstrated expression of vimentin. Large variations were found in the ability
      of FBS and HS to support growth and differentiation of EBF in monolayer culture.
      Indications of growth-promoting actions, increasing passage number as well as
      maintaining fibroblast morphology were found rather in FBS than in HS. EBF
      culturing in HS needed longer doubling and confluence time. The protein content
      of the cell pellets was higher in EBF cultured in medium containing HS than FBS.
      Alpha-smooth muscle actin seemed to be less expressed in EBF cultured in medium
      containing FBS than those in HS. CONCLUSIONS: In sum, serum addition to basal EBF
      medium enhanced EBF differentiation into myofibroblasts, and these findings are
      useful to develop in vitro fibroblast culture models that mimic in vivo
      physiological processes and to study airway disease mechanisms and remodeling.

PMID- 24886636
TI  - Association between cardiorespiratory fitness and the prevalence of metabolic
      syndrome among Korean adults: a cross sectional study.
AB  - BACKGROUND: The purpose of the current study was to investigate the association
      between cardiorespiratory fitness (CRF), measured by a simple step test, and the
      prevalence of metabolic syndrome among Korean adults, in a cross sectional
      design. METHODS: A total of 1,007 Korean adults (488 men and 519 women) who
      underwent routine health checkups were recruited. CRF was measured by Tecumseh
      step test. The National Cholesterol Education Program's Adult Treatment Panel III
      guideline was used to determine the prevalence of metabolic syndrome. A logistic
      regression was performed to reveal possible associations. RESULTS: The results of
      the study showed that a lower level of CRF was significantly associated with a
      higher prevalence of metabolic syndrome in men, but not in women. On the other
      hand, higher BMI was associated with a higher prevalence of metabolic syndrome in
      both men and women. However, BMI was not associated with fasting glucose nor
      hemoglobinA1c in men. When the combined impact of BMI and CRF on the prevalence
      of metabolic syndrome was analyzed, a significantly increased prevalence of
      metabolic syndrome was found in both men (odds ratio [OR]: 18.8, 95% Confidence
      Interval [CI]: 5.0-70.5) and women (OR: 8.1, 95% CI: 2.8-23.9) who had high BMI
      and low cardiorespiratory fitness. On the other hand, the prevalence of metabolic
      syndrome was only increased 7.9 times (95% CI: 2.0-31.2) in men and 5.4 times
      (95% CI: 1.9-15.9) in women who had high level of CRF and high BMI. CONCLUSION:
      In conclusion, the current study demonstrated the low CRF and obesity was a
      predictor for metabolic syndrome in Korean adults.

PMID- 24886637
TI  - A three-step approach for the derivation and validation of high-performing
      predictive models using an operational dataset: congestive heart failure
      readmission case study.
AB  - BACKGROUND: The aim of this study was to propose an analytical approach to
      develop high-performing predictive models for congestive heart failure (CHF)
      readmission using an operational dataset with incomplete records and changing
      data over time. METHODS: Our analytical approach involves three steps: pre
      processing, systematic model development, and risk factor analysis. For pre
      processing, variables that were absent in >50% of records were removed. Moreover,
      the dataset was divided into a validation dataset and derivation datasets which
      were separated into three temporal subsets based on changes to the data over
      time. For systematic model development, using the different temporal datasets and
      the remaining explanatory variables, the models were developed by combining the
      use of various (i) statistical analyses to explore the relationships between the
      validation and the derivation datasets; (ii) adjustment methods for handling
      missing values; (iii) classifiers; (iv) feature selection methods; and (iv)
      discretization methods. We then selected the best derivation dataset and the
      models with the highest predictive performance. For risk factor analysis, factors
      in the highest-performing predictive models were analyzed and ranked using (i)
      statistical analyses of the best derivation dataset, (ii) feature rankers, and
      (iii) a newly developed algorithm to categorize risk factors as being strong,
      regular, or weak. RESULTS: The analysis dataset consisted of 2,787 CHF
      hospitalizations at University of Utah Health Care from January 2003 to June
      2013. In this study, we used the complete-case analysis and mean-based imputation
      adjustment methods; the wrapper subset feature selection method; and four ranking
      strategies based on information gain, gain ratio, symmetrical uncertainty, and
      wrapper subset feature evaluators. The best-performing models resulted from the
      use of a complete-case analysis derivation dataset combined with the Class
      Attribute Contingency Coefficient discretization method and a voting classifier
      which averaged the results of multi-nominal logistic regression and voting
      feature intervals classifiers. Of 42 final model risk factors, discharge
      disposition, discretized age, and indicators of anemia were the most significant.
      This model achieved a c-statistic of 86.8%. CONCLUSION: The proposed three-step
      analytical approach enhanced predictive model performance for CHF readmissions.
      It could potentially be leveraged to improve predictive model performance in
      other areas of clinical medicine.

PMID- 24886638
TI  - Yoga for managing knee osteoarthritis in older women: a pilot randomized
      controlled trial.
AB  - BACKGROUND: Osteoarthritis (OA) is a common problem in older women that is
      associated with pain and disabilities. Although yoga is recommended as an
      exercise intervention to manage arthritis, there is limited evidence documenting
      its effectiveness, with little known about its long term benefits. This study's
      aims were to assess the feasibility and potential efficacy of a Hatha yoga
      exercise program in managing OA-related symptoms in older women with knee OA.
      METHODS: Eligible participants (N=36; mean age 72 years) were randomly assigned
      to 8-week yoga program involving group and home-based sessions or wait-list
      control. The yoga intervention program was developed by a group of yoga experts
      (N=5). The primary outcome was the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) total score that measures knee OA pain, stiffness,
      and function at 8 weeks. The secondary outcomes, physical function of the lower
      extremities, body mass index (BMI), quality of sleep (QOS), and quality of life
      (QOL), were measured using weight, height, the short physical performance battery
      (SPPB), the Pittsburgh Sleep Quality Index (PSQI), the Cantril Self-Anchoring
      Ladder, and the SF12v2 Health Survey. Data were collected at baseline, 4 weeks
      and 8 weeks, and 20 weeks. RESULTS: The recruitment target was met, with study
      retention at 95%. Based on ANCOVAs, participants in the treatment group exhibited
      significantly greater improvement in WOMAC pain (adjusted means [SE]) (8.3 [.67],
      5.8 [.67]; p=.01), stiffness (4.7 [.28], 3.4 [.28]; p=.002) and SPPB (repeated
      chair stands) (2.0 [.23], 2.8 [.23]; p=.03) at 8 weeks. Significant treatment and
      time effects were seen in WOMAC pain (7.0 [.46], 5.4 [.54]; p=.03), function
      (24.5 [1.8], 19.9 [1.6]; p=.01) and total scores (35.4 [2.3], 28.6 [2.1]; p=.01)
      from 4 to 20 weeks. Sleep disturbance was improved but the PSQI total score
      declined significantly at 20 weeks. Changes in BMI and QOL were not significant.
      No yoga related adverse events were observed. CONCLUSIONS: A weekly yoga program
      with home practice is feasible, acceptable, and safe for older women with knee
      OA, and shows therapeutic benefits. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01832155.

PMID- 24886639
TI  - Terminalia catappa attenuates urokinase-type plasminogen activator expression
      through Erk pathways in Hepatocellular carcinoma.
AB  - BACKGROUND: The survival rate of malignant tumors, and especially hepatocellular
      carcinoma (HCC), has not improved primarily because of uncontrolled metastasis.
      In our previous studies, we have reported that Terminalia catappa leaf extract
      (TCE) exerts antimetastasis effects on HCC cells. However, the molecular
      mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have
      not been thoroughly investigated, and remain poorly understood. METHODS: The
      activities and protein levels of u-PA were determined by casein zymography and
      western blotting. Transcriptional levels of u-PA were detected by real-time PCR
      and promoter assays. RESULTS: We found that treatment of Huh7 cells with TCE
      significantly reduced the activities, protein levels and mRNA levels of u-PA. A
      chromatin immunoprecipitation (ChIP) assay showed that TCE inhibited the
      transcription protein of nuclear factors SP-1 and NF-kappaB. TCE also did inhibit
      the effects of u-PA by reducing the phosphorylation of ERK1/2 pathway.
      CONCLUSIONS: These results show that u-PA expression may be a potent therapeutic
      target in the TCE-mediated suppression of HCC metastasis.

PMID- 24886640
TI  - Post-processing sets of tilted CT volumes as a method for metal artifact
      reduction.
AB  - BACKGROUND: Metal implants, surgical clips and other foreign bodies may cause
      'streaking' or 'star' artifacts in computed tomography (CT) reconstructions, for
      example in the vicinity of dental restorations or hip implants. The deteriorated
      image quality complicates contouring and has an adverse effect on quantitative
      planning in external beam therapy. METHODS: The potential to reduce artifacts by
      acquisition of tilted CT reconstructions from different angles of the same object
      was investigated. While each of those reconstructions still contained artifacts,
      they were not necessarily in the same place in each CT. By combining such CTs
      with complementary information, a reconstructed volume with less or even without
      artifacts was obtained. The most straightforward way to combine the co-registered
      volumes was to calculate the mean or median per voxel. The method was tested with
      a calibration phantom featuring a titanium insert, and with a human skull
      featuring multiple dental restorations made from gold and steel. The performance
      of the method was compared to established metal artifact reduction (MAR)
      algorithms. Dose reduction was tested. RESULTS: In a visual comparison, streaking
      artifacts were strongly reduced and details in the vicinity of metal foreign
      bodies became much more visible. In case of the calibration phantom, average bias
      in Hounsfield units was reduced by 94% and per-voxel-errors and noise were
      reduced by 83%. In case of the human skull, bias was reduced by 95% and noise was
      reduced by 94%. The performance of the method was visually superior and
      quantitatively compareable to established MAR algorithms. Dose reduction was
      viable. CONCLUSIONS: A simple post-processing method for MAR was described which
      required one or more complementary scans but did not rely on any a priori
      information. The method was computationally inexpensive. Performance of the
      method was quantitatively comparable to established algorithms and visually
      superior in a direct comparison. Dose reduction was demonstrated, artifacts could
      be reduced without compromising total dose to the patient.

PMID- 24886641
TI  - Switching and emergence of CTL epitopes in HIV-1 infection.
AB  - BACKGROUND: Human Leukocyte Antigen (HLA) class I restricted Cytotoxic T
      Lymphocytes (CTLs) exert substantial evolutionary pressure on HIV-1, as evidenced
      by the reproducible selection of HLA-restricted immune escape mutations in the
      viral genome. An escape mutation from tyrosine to phenylalanine at the 135th
      amino acid (Y135F) of the HIV-1 nef gene is frequently observed in patients with
      HLA-A*24:02, an HLA Class I allele expressed in ~70% of Japanese persons. The
      selection of CTL escape mutations could theoretically result in the de novo
      creation of novel epitopes, however, the extent to which such dynamic "CTL
      epitope switching" occurs in HIV-1 remains incompletely known. RESULTS: Two
      overlapping epitopes in HIV-1 nef, Nef126-10 and Nef134-10, elicit the most
      frequent CTL responses restricted by HLA-A*24:02. Thirty-five of 46 (76%) HLA
      A*24:02-positive patients harbored the Y135F mutation in their plasma HIV-1 RNA.
      Nef codon 135 plays a crucial role in both epitopes, as it represents the C
      terminal anchor for Nef126-10 and the N-terminal anchor for Nef134-10. While the
      majority of patients with 135F exhibited CTL responses to Nef126-10, none
      harboring the "wild-type" (global HIV-1 subtype B consensus) Y135 did so,
      suggesting that Nef126-10 is not efficiently presented in persons harboring Y135.
      Consistent with this, peptide binding and limiting dilution experiments confirmed
      F, but not Y, as a suitable C-terminal anchor for HLA-A*24:02. Moreover,
      experiments utilizing antigen specific CTL clones to recognize endogenously
      expressed peptides with or without Y135F indicated that this mutation disrupted
      the antigen expression of Nef134-10. Critically, the selection of Y135F also
      launched the expression of Nef126-10, indicating that the latter epitope is
      created as a result of escape within the former. CONCLUSIONS: Our data represent
      the first example of the de novo creation of a novel overlapping CTL epitope as a
      direct result of HLA-driven immune escape in a neighboring epitope. The robust
      targeting of Nef126-10 following transmission (or in vivo selection) of HIV-1
      containing Y135F may explain in part the previously reported stable plasma viral
      loads over time in the Japanese population, despite the high prevalence of both
      HLA-A*24:02 and Nef-Y135F in circulating HIV-1 sequences.

PMID- 24886644
TI  - A case of extraperitoneal stoma-associated internal hernia after abdominoperineal
      resection.
AB  - Published reports concerning internal hernias after extraperitoneal stoma
      construction are scarce. In our present report, we describe the case of a 56-year
      old man who was referred to our hospital for the treatment of rectal cancer. He
      underwent abdominoperineal resection of the rectum with sigmoidostomy using an
      extraperitoneal route. On the ninth postoperative day, the patient experienced
      sudden and intense abdominal pain and was diagnosed with strangulation of the
      small intestine due to a stoma-associated internal hernia. Therefore, an
      emergency laparotomy was performed. The surgical findings showed that the small
      intestine protruded through the space between the sigmoid colon loop and the
      abdominal wall in a cranial-to-caudal direction. The strangulated portion of the
      small intestine was recovered, and the orifice of herniation was closed. No
      recurrence of internal herniation was observed during the follow-up period. 

PMID- 24886643
TI  - Elongated TCR alpha chain CDR3 favors an altered CD4 cytokine profile.
AB  - BACKGROUND: CD4 T lymphocyte activation requires T cell receptor (TCR) engagement
      by peptide/MHC (major histocompatibility complex) (pMHC). The TCR complementarity
      determining region 3 (CDR3) contains variable alpha and beta loops critical for
      pMHC recognition. During any immune response, tuning of TCR usage through
      progressive clonal selection occurs. Th1 and Th2 cells operate at different
      avidities for activation and display distinct transcriptional programs, although
      polarization may be plastic, influenced by pathogens and cytokines. We therefore
      hypothesized that CDR3alphabeta sequence features may intrinsically influence CD4
      phenotype during progression of a response. RESULTS: We show that CD4
      polarization involves distinct CDR3alpha usage: Th1 and Th17 cells favored short
      TCR CDR3alpha sequences of 12 and 11 amino acids, respectively, while Th2 cells
      favored elongated CDR3alpha loops of 14 amino acids, with lower predicted
      affinity. The dominant Th2- and Th1-derived TCRalpha sequences with 14 amino acid
      CDR3 loops and 12 amino acid CDR3 loops, respectively, were expressed in TCR
      transgenics. The functional impact of these TCRalpha transgenes was assessed
      after in vivo priming with a peptide/adjuvant. The short, Th1-derived receptor
      transgenic T cell lines made IFNgamma, but not IL-4, 5 or 13, while the
      elongated, Th2-derived receptor transgenic T cell lines made little or no
      IFNgamma, but increased IL-4, 5 and 13 with progressive re-stimulations, mirrored
      by GATA-3 up-regulation. T cells from primed Th2 TCRalpha transgenics selected
      dominant TCR Vbeta expansions, allowing us to generate TCRalphabeta transgenics
      carrying the favored, Th2-derived receptor heterodimer. Primed T cells from
      TCRalphabeta transgenics made little or no IL-17 or IFNgamma, but favored IL-9
      after priming with Complete Freund's adjuvant and IL-4, 5, 9, 10 and 13 after
      priming with incomplete Freund's. In tetramer-binding studies, this transgenic
      receptor showed low binding avidity for pMHC and polarized T cell lines show TCR
      avidity for Th17 > Th1 > Th2. While transgenic expression of a Th2-derived,
      'elongated' TCR-CDR3alpha and the TCRalphabeta pair, clearly generated a program
      shifted away from Th1 immunity and with low binding avidity, cytokine-skewing
      could be over-ridden by altering peptide challenge dose. CONCLUSION: We propose
      that selection from responding clones with distinctive TCRs on the basis of
      functional avidity can direct a preference away from Th1 effector responses,
      favoring Th2 cytokines.

PMID- 24886642
TI  - Differential levels of amino acid transporters System L and ASCT2, and the mTOR
      protein in placenta of preeclampsia and IUGR.
AB  - BACKGROUND: Sufficient amino acid transport activity (AAT) is indispensable for
      appropriate fetal growth. Studies suggest that placental nutrient uptake activity
      is responsive to both maternal and fetal nutrient demands. We hypothesize that
      under conditions of limited nutrient availability to the fetus, as often present
      in preeclampsia, intrauterine growth restriction (IUGR), and insufficient weight
      gain during pregnancy, a general adaptive response aimed to increase amino acid
      transport activity may be observed in the placenta. METHOD: A total of 40
      placentas from full-term (n = 10) and pre-term (average gestational period = 34.8
      weeks, n = 10) normal pregnancies, IUGR (n = 10), and preeclampsia (n = 10)
      associated pregnancies were looked at by immunohistochemistry followed by
      relative qualitative scoring to compare expression levels and localization of
      System L, ASCT2, and mTOR proteins. RESULT: Microvillous syncytiotrophoblast (ST)
      in placenta of pregnancies complicated by IUGR or preeclampsia (PE) showed
      significant increases in the levels of System L amino acid transport proteins
      4F2hc and LAT1 compared to both full-term control and pre-term (early gestation
      control) pregnancies seperately (p < 0.05). Elevated mTOR protein was uniquely
      higher in IUGR placentas compared to full-term controls (P = 0.0026). Total
      cellular ASCT2 transporter protein levels were similar in all groups, however,
      levels of ASCT2 protein localized to the ST microvillous membrane (MVM) were
      significantly lower in IUGR compared to both full-term and pre-term pregnancies
      (P = 0.0006, 0.03, respectively). Additionally, ASCT2 and mTOR protein levels
      were positively associated with maternal pre-pregnancy BMI (P = 0.046, 0.048,
      respectively). CONCLUSION: There are three important findings based upon the
      present study. First, in conditions of limited nutrient availability, such as PE
      or IUGR, there is an overall increase in the level of System L and mTOR protein
      expression in the ST, suggestive of an adaptive response. Second, a decrease in
      ASCT2 protein at the ST MVM suggests a post-translational event that may decrease
      AAT activity in IUGR placentas. Third, a physiological link between transporter
      expression and pre-pregnancy BMI is suggested based upon a positive association
      observed with ASCT2 and mTOR expression values.

PMID- 24886645
TI  - Clinical and optic coherence tomography findings of focal choroidal excavation in
      Chinese patients.
AB  - BACKGROUND: To describe the clinical and optical coherence tomography (OCT)
      features of focal choroidal excavation in Chinese patients. METHODS:
      Retrospectively, thirty-seven eyes (in 31 patients) that demonstrated focal
      choroidal excavation on spectral-domain OCT were collected. Their clinical
      characteristics and other features were also collected and analyzed. RESULTS: In
      total, 42 focal choroidal excavations were identified in 31 patients, including
      25 unilateral and 6 bilateral (37 eyes). The abnormal changes in these eyes with
      choroidal excavation were more prominent at the outer part of the neuro-retina,
      the retinal pigment epithelium (RPE) and the choroid. The average transverse
      diameter and depth of the excavations were 670.8 MUm and 106.9 MUm, respectively.
      In addition to the conforming and nonconforming types, the excavations could also
      be classified into 2 types according to their shape: type 1 - small with a sharp,
      cut-down contour; and type 2 - slightly larger with a gradual edge. The
      transverse diameter/depth ratio of the two types were significantly different
      (type1: 4.57 +/- 1.65, type 2: 10.0 +/- 5.2; p = 0.000). Four central serous
      chorioretinopathy (CSCR) cases were confirmed by fluorescein angiography; in
      these cases, the retinal detachment was larger than the area of excavation, and
      the inner segment/outer segment (IS/OS) and external limiting membrane (ELM) were
      above those of the normal part. Concomitant CNV was also found in another 2
      cases. CONCLUSIONS: Focal choroidal excavation was not uncommon in Chinese
      patients. The choroid and the RPE at the excavation were impaired or vulnerable
      to other damage. Additionally, OCT might be useful in the differentiation between
      nonconforming excavations and ones with CSCR.

PMID- 24886646
TI  - Barriers and facilitators to pre-exposure prophylaxis (PrEP) eligibility
      screening and ongoing HIV testing among target populations in Bondo and Rarieda,
      Kenya: results of a consultation with community stakeholders.
AB  - BACKGROUND: As pre-exposure prophylaxis (PrEP) moves closer to availability in
      developing countries, practical considerations for implementation become
      important. We conducted a consultation with district-level community stakeholders
      experienced in HIV-prevention interventions with at-risk populations in Bondo and
      Rarieda, Kenya to generate locally grounded approaches to the future rollout of
      oral PrEP to four populations: fishermen, widows, female sex workers, and
      serodiscordant couples. METHODS: The 20 consultation participants represented the
      Ministry of Health, faith- and community-based organizations, health facilities,
      community groups, and nongovernmental organizations. Participants divided into
      breakout groups and followed a structured discussion guide asking them to
      identify barriers to implementing HIV-prevention interventions (including PrEP)
      with each population. Questions also solicited solutions for addressing these
      barriers, as well as other facilitators for PrEP implementation. In particular,
      questions focused on how to encourage people to screen for PrEP eligibility by
      having HIV and other blood tests and how to encourage compliance with ongoing HIV
      testing. RESULTS: The barriers and facilitators/solutions discussants provided
      were frequently population-specific, but there were also broad-level similarities
      across populations. Service delivery barriers to HIV-prevention interventions
      concerned the need for staff trained to address the needs of particular
      populations. Service delivery facilitators to provision of ongoing HIV testing
      consisted of offering testing options besides facility-based testing. Stigma was
      the main community-level barrier for all groups, whereas barriers at the level of
      target populations included mobility; lifestyle and life circumstances,
      especially cultural norms among fishermen and widows; and fears, lack of
      awareness, and misinformation. Proposed facilitators and strategies for
      addressing community- and population-level barriers included topic-specific
      education within the populations and community, involvement of partners and
      family members, mass HIV testing, and peer educators. Barriers to PrEP uptake
      included non-adherence to pill taking and missing clinic visits. For drug
      adherence, facilitators were counselling and involving family members.
      Discussants suggested that client reminders, e.g., home visits, were needed to
      encourage clients to keep their clinic appointments. CONCLUSIONS: Strategies for
      encouraging eligibility screening and ongoing HIV testing will have local and
      population-specific aspects. Our results nonetheless apply to similar populations
      throughout sub-Saharan Africa and reach beyond oral PrEP to other ARV-based PrEP
      formulations.

PMID- 24886647
TI  - The effect of transcutaneous electrical acupoint stimulation on pregnancy rates
      in women undergoing in vitro fertilization: a study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: The latest meta-analysis demonstrated that acupuncture improves
      pregnancy rates among women undergoing in vitro fertilization-embryo transfer
      (IVF-ET), and surface acupoint stimulation, such as transcutaneous electrical
      acupoint stimulation (TEAS), may have the same or better potential.
      METHODS/DESIGN: To explore the effect of TEAS on the clinical pregnancy rate
      (CPR) and live birth rate (LBR) compared with real acupuncture and controls in
      women undergoing IVF, a multicenter, randomized controlled trial will be
      conducted. The inclusion criteria are the following: infertile women <40 years of
      age undergoing a fresh IVF or intracytoplasmic sperm injection cycle, and the
      study will be restricted to women with the potential for a lower success rate as
      defined by two or more previous unsuccessful ETs (fresh or frozen). Those who
      have severe illnesses possibly precluding IVF or pregnancy, have FSH levels
      greater than 20 IU/L, received donor eggs, had been previously randomized for
      this study or had undergone acupuncture (in any modality) as infertility
      treatment will be excluded. The subjects will be randomly assigned to the TEAS
      group (IVF + TEAS), the electro-acupuncture (EA) group (IVF + EA), or the control
      group (only IVF). A total sample size of 2,220 women is required to detect
      differences in CPR among the three groups. TEAS or EA treatments will start once
      every two or three days from day 3 of menstruation in the ovarian stimulation
      cycle until the day of ET. The parameters of TEAS or EA will be the following: a
      frequency of 2/100 Hz, a moderate electrical current of 3 to 5 mA for TEAS and
      0.8 to 1.0 mA for EA. The primary outcome is CPR. Secondary outcomes are LBR, the
      number of oocytes aspirated and the total gonadotropin dose used in the
      stimulation cycle. DISCUSSION: This study will provide significant evidence for
      using a new method (TEAS) in IVF. TRIAL REGISTRATION: ClinicalTrials.govID:
      NCT01608048 (05/24/2012).

PMID- 24886649
TI  - Prevalence, determinants and systems-thinking approaches to optimal hypertension
      control in West Africa.
AB  - BACKGROUND: In West Africa, hypertension, once rare, has now emerged as a
      critical health concern and the trajectory is upward and factors are complex. The
      true magnitude of hypertension in some West African countries, including in-depth
      knowledge of underlying risk factors is not completely understood. There is also
      a paucity of research on adequate systems-level approaches designed to mitigate
      the growing burden of hypertension in the region. AIMS: In this review, we
      thematically synthesize available literature pertaining to the prevalence of
      hypertension in West Africa and discuss factors that influence its diagnosis,
      treatment and control. We aimed to address the social and structural determinants
      influencing hypertension in the sub-region including the effects of urbanization,
      health infrastructure and healthcare workforce. FINDINGS: The prevalence of
      hypertension in West Africa has increased over the past decade and is rising
      rapidly with an urban-rural gradient that places higher hypertension prevalence
      on urban settings compared to rural settings. Overall levels of awareness of
      one's hypertension status remain consistently low in West African. Structural and
      economic determinants related to conditions of poverty such as insufficient
      finances have a direct impact on adherence to prescribed antihypertensive
      medications. Urbanization contributes to the increasing incidence of hypertension
      in the sub-region and available evidence indicates that inadequate health
      infrastructure may act as a barrier to optimal hypertension control in West
      Africa. CONCLUSION: Given that optimal hypertension control in West Africa
      depends on multiple factors that go beyond simply modifying the behaviors of the
      individuals alone, we conclude by discussing the potential role systems-thinking
      approaches can play to achieve optimal control in the sub-region. In the context
      of recent advances in hypertension management including new therapeutic options
      and innovative solutions to expand health workforce so as to meet the high demand
      for healthcare, the success of these strategies will rely on a new understanding
      of the complexity of human behaviors and interactions most aptly framed from a
      systems-thinking perspective.

PMID- 24886648
TI  - Stem cell therapy for the treatment of early stage avascular necrosis of the
      femoral head: a systematic review.
AB  - BACKGROUND: Avascular necrosis (AVN) of the femoral head (FH) is believed to be
      caused by a multitude of etiologic factors and is associated with significant
      morbidity in younger populations. Eventually, the disease progresses and results
      in FH collapse. Thus, a focus on early disease management aimed at joint
      preservation by preventing or delaying progression is key. The use of stem cells
      (SC) for the treatment of AVN of the FH has been proposed. We undertook a
      systematic review of the medical literature examining the use of SC for the
      treatment of early stage (precollapse) AVN of the FH, in both pre-clinical and
      clinical studies. METHODS: Data collected included: Pre-clinical studies - model
      of AVN, variety and dosage of SC, histologic and imaging analyses. Clinical
      studies - study design, classification and etiology of AVN, SC dosage and
      treatment protocol, incidence of disease progression, patient reported outcomes,
      volume of necrotic lesion and hip survivorship. RESULTS: In pre-clinical studies,
      the use of SC uniformly demonstrated improvements in osteogenesis and
      angiogenesis, yet source of implanted SC was variable. In clinical studies,
      groups treated with SC showed significant improvements in patient reported
      outcomes; however hip survivorship was not affected. Discrepancies regarding dose
      of SC, AVN etiology and disease severity were present. CONCLUSIONS: Routine use
      of this treatment method will first require further research into dose and
      quality optimization as well as confirmed improvements in hip survivorship.

PMID- 24886650
TI  - Acceptance of a malaria vaccine by caregivers of sick children in Kenya.
AB  - BACKGROUND: Several malaria vaccines are currently in clinical trials and are
      expected to provide an improved strategy for malaria control. Prior to
      introduction of a new vaccine, policymakers must consider the socio cultural
      environment of the region to ensure widespread community approval. This study
      investigated the acceptance of a malaria vaccine by child caregivers and analysed
      factors that influence these. METHODS: Interviews from a standard questionnaire
      were conducted with 2,003 caregivers at 695 randomly selected health facilities
      across Kenya during the Kenya Service Provision Assessment Survey 2010.
      Multinomial regression of quantitative data was conducted using STATA to analyse
      determinants of caregivers accepting malaria vaccination of their child. RESULTS:
      Mothers represented 90% of caregivers interviewed who brought their child to the
      health facility, and 77% of caregivers were 20-34 years old. Overall, 88% of
      respondents indicated that they would accept a malaria vaccine, both for a child
      in their community and their own child. Approval for a vaccine was highest in
      malaria-endemic Nyanza Province at 98.9%, and lowest in the seasonal transmission
      area of North Eastern Province at 23%. Although 94% of respondents who had
      attended at least some school reported they would accept the vaccine for a child,
      only 56% of those who had never attended school would do so. The likelihood of
      accepting one's own child to be immunized was correlated with province,
      satisfaction with health care services in the facility attended, age of the
      caregiver, and level of education. CONCLUSIONS: Results from this study indicate
      a need for targeted messages and education on a malaria vaccine, particularly for
      residents of regions where acceptance is low, older caregivers, and those with
      low literacy and school-attendance levels. This study provides critical evidence
      to inform policy for a new malaria vaccine that will support its timely and
      comprehensive uptake in Kenya.

PMID- 24886652
TI  - Biomarkers of early sepsis may be correlated with outcome.
AB  - BACKGROUND: Sepsis causes high mortality, and the mortality due to secondary
      infections is even higher. No studies to date have investigated the time from the
      primary infection to death due to a secondary infection; similarly, the factors
      that are significantly different in sepsis survivors relative to non-survivors or
      in severe sepsis patients who suffered a late death relative to those who recover
      have not been explored. We hypothesized that patients who survive sepsis have a
      weaker pro-inflammatory response than those who do not and that the mid-term
      survivors (which acquire secondary infections) would have a pronounced anti
      inflammatory response (making them susceptible to infection); this hypothesis was
      verified in this study. METHODS: We examined 24 patients with severe sepsis; the
      patients were subdivided by outcome into early death (n=5), mid-term survival
      (survival through severe sepsis but death within six months or continued
      hospitalization for six months, n=6), and long-term survival (recovery and
      survival for more than six months, n=13) groups. The levels of CD3+, CD4+, CD8+,
      and CD19+ lymphocytes were analyzed by flow cytometry, and the plasma levels of
      carbonic anhydrase IX (CA IX), MCP-1, IL-6, IL-7, IL-8, and IL-10 were measured
      by ELISA on days 0, 1, 2, and 3. A statistical comparison of the variables in the
      groups was conducted using a mixed model. RESULTS: The plasma levels of MCP-1, IL
      6, and IL-8 in early death and survivors were significantly different, and all
      had p values<0.01. The plasma levels of MCP-1, IL-6, and IL-8 were also
      significantly different in mid-term survivors and long-term survivors, with p
      values of <0.01, 0.04, and <0.01, respectively. CONCLUSIONS: Our data support the
      hypothesis that survivors have a weaker pro-inflammatory response than non
      survivors, but the mid-term survivors did not have a more pronounced anti
      inflammatory response. The levels of pro-inflammatory cytokines in the mid-term
      and long-term survivors were significantly different.

PMID- 24886651
TI  - Toxoplasma infection in pregnant women: a current status in Songklanagarind
      hospital, southern Thailand.
AB  - BACKGROUND: Toxoplasmosis, being one of the TORCH's infections in pregnant women,
      is caused by Toxoplasma gondii, an obligate intracellular protozoan parasite.
      This parasitic infection in pregnancy congenitally causes severe outcomes to
      their fetus and newborn. This study aimed to determine the seroprevalence and
      stages of Toxoplasma infection in pregnant women and its associated risks
      exposures. METHODS: The study was conducted within the pregnant women attending
      the antenatal clinic (ANC) at Songklanagarind hospital, Hat Yai, Songkhla
      province, Thailand. The sera of a total of 760 consecutive pregnant women were
      screened using standard commercial ELISA kits for detection of anti-Toxoplasma
      IgG and IgM antibodies. IgG avidity in the seropositive for both anti-Toxoplasma
      IgG and IgM antibodies were also assessed. The pregnant women's socio
      demographic, obstetrics and risk factors associated with Toxoplasma
      seropositivity data were analyzed using univariate and multivariate analyses.
      RESULTS: From the total 760 pregnant women, 190 (25%, 95% CI = 22.05-28.20) were
      positive for anti-Toxoplasma antibodies. Of these, 167 (22.0%, 95% CI = 19.0
      25.0) were positive for only anti-Toxoplasma IgG antibody and 23 (3.0%, 95% CI =
      2.0-4.0) were positive for both anti-Toxoplasma IgG and IgM antibodies. All these
      samples were high avidity, indicated the infection occured prior to four to five
      months. By applying statistical univariate analysis, age group, occupation and
      sources of drinking water showed a significant association with Toxoplasma
      seropositivity (p < 0.05). Multivariate logistic regression analysis further
      indicated that the significant factors associated with Toxoplasma seropositivity
      are age >=26 (OR = 1.65, 95% CI = 1.11-2.44), working as laborer (OR = 1.57, 95%
      CI = 1.13-2.18) and drinking unclean (piped/tap/rain) water (OR = 1.75, 95% CI =
      1.08-2.84). CONCLUSION: The pregnant women in the active age group, working as
      laborers and exposure to unclean drinking water from various sources were at
      higher risk of Toxoplasma infection. Therefore, health education and the
      awareness of risk exposures regarding this parasitic disease are required to
      minimize the effects of this parasitic infection in pregnant women as well as in
      the general population.

PMID- 24886654
TI  - Long-term risk of stroke after transient ischaemic attack: a hospital-based
      validation of the ABCD2 rule.
AB  - BACKGROUND: The ABCD2 clinical prediction rule is a seven point summation of
      clinical factors independently predictive of stroke risk. The purpose of this
      cohort study is to validate the ABCD2 rule in a Bulgarian hospital up to three
      years after TIA. METHODS: All consecutive admissions to an emergency department
      with symptoms of a first TIA were included. Baseline data and clinical
      examinations including the ABCD2 scores were documented by neurologists.
      Discrimination and calibration performance was examined using ABCD2 cut-off
      scores of >=3, >=4 and >=5 points, consistent with the international guidelines.
      The Hosmer-Lemeshow test was used to examine calibration between the observed and
      expected outcomes as predicted by ABCD2 score within the logistic regression
      analysis. RESULTS: Eighty-nine patients were enrolled to the study with a mean
      age of 63 years (+/- 12 years). Fifty-nine percent (n = 53) of the study
      population was male. Seven strokes (7.8%) occurred within the first year and six
      further strokes within the three-year follow-up period. There was no incident of
      stroke within the first 90 days after TIA. The rule demonstrated good predictive
      (OR = 1.58, 95% CI 1.09-2.29) and discriminative performance (AUCROC = 0.72, 95%
      CI 0.58-0.86), as well as a moderate calibration performance at three years.
      CONCLUSION: This validation of the ABCD2 rule in a Bulgarian hospital
      demonstrates that the rule has good predictive and discriminative performance at
      three years. The ABCD2 is quick to administer and may serve as a useful tool to
      assist clinicians in the long-term management of individuals with TIA.

PMID- 24886653
TI  - Analysis of rare variations reveals roles of amino acid residues in the N
      terminal extracellular domain of nicotinic acetylcholine receptor (nAChR) alpha6
      subunit in the functional expression of human alpha6*-nAChRs.
AB  - BACKGROUND: Functional heterologous expression of naturally-expressed and
      apparently functional mammalian alpha6*-nicotinic acetylcholine receptors
      (nAChRs; where '*' indicates presence of additional subunits) has been difficult.
      Here we wanted to investigate the role of N-terminal domain (NTD) residues of
      human (h) nAChR alpha6 subunit in the functional expression of halpha6*-nAChRs.
      To this end, instead of adopting random mutagenesis as a tool, we used 15 NTD
      rare variations (i.e., Ser43Pro, Asn46Lys, Asp57Asn, Arg87Cys, Asp92Glu,
      Arg96His, Glu101Lys, Ala112Val, Ser156Arg, Asn171Lys, Ala184Asp, Asp199Tyr,
      Asn203Thr, Ile226Thr and Ser233Cys) in nAChR halpha6 subunit to probe for their
      effect on the functional expression of halpha6*-nAChRs. RESULTS: N-terminal alpha
      helix (Asp57); complementary face/inner beta-fold (Arg87 or Asp92) and principal
      face/outer beta-fold (Ser156 or Asn171) residues in the halpha6 subunit are
      crucial for functional expression of the halpha6*-nAChRs as variations in these
      residues reduce or abrogate the function of halpha6hbeta2*-, halpha6hbeta4- and
      halpha6hbeta4hbeta3-nAChRs. While variations at residues Ser43 or Asn46 (both in
      N-terminal alpha-helix) in halpha6 subunit reduce halpha6hbeta2*-nAChRs function
      those at residues Arg96 (beta2-beta3 loop), Asp199 (loop F) or Ser233 (beta10
      strand) increase halpha6hbeta2*-nAChR function. Similarly substitution of NTD
      alpha-helix (Asn46), loop F (Asp199), loop A (Ala112), loop B (Ala184), or loop C
      (Ile226) residues in halpha6 subunit increase the function of halpha6hbeta4
      nAChRs. All other variations in halpha6 subunit do not affect the function of
      halpha6hbeta2*- and halpha6hbeta4*-nAChRs. Incorporation of nAChR hbeta3 subunits
      always increase the function of wild-type or variant halpha6hbeta4-nAChRs except
      for those of halpha6(D57N, S156R, R87C or N171K)hbeta4-nAChRs. It appears
      Asp57Lys, Ser156Arg or Asn171Lys variations in halpha6 subunit drive the
      halpha6hbeta4hbeta3-nAChRs into a nonfunctional state as at spontaneously open
      halpha6(D57N, S156R or N171K)hbeta4hbeta3V9'S-nAChRs (V9'S; transmembrane II 9'
      valine-to-serine mutation) agonists act as antagonists. Agonist sensitivity of
      halpha6hbeta4- and/or halpha6hbeta4hbeta3-nAChRs is nominally increased due to
      Arg96His, Ala184Asp, Asp199Tyr or Ser233Cys variation in halpha6 subunit.
      CONCLUSIONS: Hence investigating functional consequences of natural variations in
      nAChR halpha6 subunit we have discovered additional bases for cell surface
      functional expression of various subtypes of halpha6*-nAChRs. Variations
      (Asp57Asn, Arg87Cys, Asp92Glu, Ser156Arg or Asn171Lys) in halpha6 subunit that
      compromise halpha6*-nAChR function are expected to contribute to individual
      differences in responses to smoked nicotine.

PMID- 24886655
TI  - Long-term outcomes after video-assisted thoracic surgery (VATS) lobectomy versus
      lobectomy via open thoracotomy for clinical stage IA non-small cell lung cancer.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy is a standard
      treatment for lung cancer. This study retrospectively compared long-term outcomes
      after VATS lobectomy versus lobectomy via open thoracotomy for clinical stage IA
      non-small cell lung cancer (NSCLC). METHODS: From July 2002 to June 2012, 160
      patients were diagnosed with clinical stage IA NSCLC and underwent lobectomy. Of
      these, 114 underwent VATS lobectomy and 46 underwent lobectomy via open
      thoracotomy. RESULTS: The 5-year disease-free survival (DFS) rate was 88.0% in
      the VATS group and 77.1% in the thoracotomy group for clinical stage IA NSCLC (p
      = 0.1504), and 91.5% in the VATS group and 93.8% in the thoracotomy group for
      pathological stage IA NSCLC (p = 0.2662). The 5-year overall survival (OS) rate
      was 94.1% in the VATS group and 81.8% in the thoracotomy group for clinical stage
      IA NSCLC (p = 0.0268), and 94.8% in the VATS group and 96.2% in the thoracotomy
      group for pathological stage IA NSCLC (p = 0.5545). The rate of accurate
      preoperative staging was 71.9% in the VATS group and 56.5% in the thoracotomy
      group (p = 0.2611). Inconsistencies between the clinical and pathological stages
      were mainly related to tumor size, nodal status, and pleural invasion. Local
      recurrence occurred for one lesion in the VATS group and six lesions (five
      patients) in the thoracotomy group (p = 0.0495). CONCLUSIONS: The DFS and OS were
      not inferior after VATS compared with thoracotomy. Local control was
      significantly better after VATS than after thoracotomy. Preoperative staging
      lacked sufficient accuracy.

PMID- 24886657
TI  - The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation
      and metastasis in gastric cancer.
AB  - BACKGROUND: FOXO4, a member of the FOXO family of transcription factors, is
      currently the focus of intense study. Its role and function in gastric cancer
      have not been fully elucidated. The present study was aimed to investigate the
      expression profile of FOXO4 in gastric cancer and the effect of FOXO4 on cancer
      cell growth and metastasis. METHODS: Immunohistochemistry, Western blotting and
      qRT-PCR were performed to detect the FOXO4 expression in gastric cancer cells and
      tissues. Cell biological assays, subcutaneous tumorigenicity and tail vein
      metastatic assay in combination with lentivirus construction were performed to
      detect the impact of FOXO4 to gastric cancer in proliferation and metastasis in
      vitro and in vivo. Confocal and qRT-PCR were performed to explore the mechanisms.
      RESULTS: We found that the expression of FOXO4 was decreased significantly in
      most gastric cancer tissues and in various human gastric cancer cell lines. Up
      regulating FOXO4 inhibited the growth and metastasis of gastric cancer cell lines
      in vitro and led to dramatic attenuation of tumor growth, and liver and lung
      metastasis in vivo, whereas down-regulating FOXO4 with specific siRNAs promoted
      the growth and metastasis of gastric cancer cell lines. Furthermore, we found
      that up-regulating FOXO4 could induce significant G1 arrest and S phase reduction
      and down-regulation of the expression of vimentin. CONCLUSION: Our data suggest
      that loss of FOXO4 expression contributes to gastric cancer growth and
      metastasis, and it may serve as a potential therapeutic target for gastric
      cancer.

PMID- 24886656
TI  - A comparison study between periosteum and resorbable collagen membrane on iliac
      block bone graft resorption in the rabbit calvarium.
AB  - BACKGROUND: To compare the different resorption patterns between resorbable
      membrane barrier and periosteum after iliac block bone grafting radiographically
      and histologically. METHODS: Eighteen mature male rabbits weighing from 2.0 to
      2.5 kg were used. The recipient site was the rabbit skull, and autogenous iliac
      bone was used as the grafting material. The harvested iliac block bones were
      divided in the following groups: autogenous iliac block bone with preservation of
      the periosteum (the periosteum group), autogenous iliac block bone covered with a
      resorbable collagen membrane (Biomesh(r), Samyang Co, Korea) after removing the
      periosteum (the collagen membrane group), and autogenous iliac block bones with
      removal of the periosteum (the control group). In each experimental group,
      periosteum or resorbable collagen membrane of the donor site was fixed directed
      to the periosteum of the recipient site. The specimens were examined
      macroscopically, radiographically, histologically, and histomorphometrically at
      every 2, 4, and 8 weeks. RESULTS: All groups presented excellent bone graft
      healing state without inflammation, dehiscence, or displacement. The radiolucency
      increased from mild to moderate in all groups over the experiment. The mean
      thickness of the upper end of the cortical iliac bone graft was statistically
      significantly different between the control group and the periosteum group,
      between the four-week and eight-week control group, and between the four- week
      and eight-week periosteum group (p & 0.05). CONCLUSION: This study suggests that
      both the periosteum and the resorbable collagen membrane may help to prevent soft
      tissue infiltration into the bone graft and to reduce bone graft resorption
      compared to block graft alone.

PMID- 24886658
TI  - Molecular typing of Salmonella enterica serovar Enteritidis isolates from food
      producing animals in Japan by multilocus variable-number tandem repeat analysis:
      evidence of clonal dissemination and replacement.
AB  - BACKGROUND: Salmonella enterica serovar Enteritidis is a zoonotic pathogen. Human
      infections are associated with contaminated eggs and egg products. In Japan,
      since 1989, the incidence of food-borne disease caused by S. Enteritidis has
      increased and a pandemic has occurred; however, little is known about changes
      that occurred before and after this pandemic event in the dominant lineage of
      isolates from food-producing animals. This study aimed to determine the S.
      Enteritidis lineages in Japan over the last few decades by using multilocus
      variable-number tandem repeat analysis (MLVA). FINDINGS: MLVA was used to analyse
      79 S. Enteritidis isolates collected from chickens (n = 63), cattle (n = 12),
      pigs (n = 2), and goats (n = 2) during 1975-2009. The S. Enteritidis isolates
      showed 14 different MLVA allele combinations, which were classified into two
      major clusters (A and C) and a minor cluster (B). All the 62 isolates in cluster
      A were isolated after 1988, whereas 13 of the 17 isolates belonging to cluster B
      and C were isolated before 1989. CONCLUSIONS: The MLVA results showed that
      cluster C was predominant before 1989, and isolates in cluster A disseminated
      since 1989 and replaced the previous dominant clone, suggesting that isolates of
      cluster A originated from imported S. Enteritidis infection.

PMID- 24886660
TI  - An inverse method to determine the mechanical properties of the iris in vivo.
AB  - BACKGROUND: Understanding the mechanical properties of the iris can help to have
      an insight into the eye diseases with abnormalities of the iris morphology.
      Material parameters of the iris were simply calculated relying on the ex vivo
      experiment. However, the mechanical response of the iris in vivo is different
      from that ex vivo, therefore, a method was put forward to determine the material
      parameters of the iris using the optimization method in combination with the
      finite element method based on the in vivo experiment. MATERIAL AND METHODS:
      Ocular hypertension was induced by rapid perfusion to the anterior chamber,
      during perfusion intraocular pressures in the anterior and posterior chamber were
      record by sensors, images of the anterior segment were captured by the ultrasonic
      system. The displacement of the characteristic points on the surface of the iris
      was calculated. A finite element model of the anterior chamber was developed
      using the ultrasonic image before perfusion, the multi-island genetic algorithm
      was employed to determine the material parameters of the iris by minimizing the
      difference between the finite element simulation and the experimental
      measurements. RESULTS: Material parameters of the iris in vivo were identified as
      the iris was taken as a nearly incompressible second-order Ogden solid. Values of
      the parameters MU1, alpha1, MU2 and alpha2 were 0.0861 +/- 0.0080 MPa, 54.2546 +/
      12.7180, 0.0754 +/- 0.0200 MPa, and 48.0716 +/- 15.7796 respectively. The
      stability of the inverse finite element method was verified, the sensitivity of
      the model parameters was investigated. CONCLUSION: Material properties of the
      iris in vivo could be determined using the multi-island genetic algorithm coupled
      with the finite element method based on the experiment.

PMID- 24886659
TI  - Network analysis identifies protein clusters of functional importance in juvenile
      idiopathic arthritis.
AB  - INTRODUCTION: Our objective was to utilise network analysis to identify protein
      clusters of greatest potential functional relevance in the pathogenesis of
      oligoarticular and rheumatoid factor negative (RF-ve) polyarticular juvenile
      idiopathic arthritis (JIA). METHODS: JIA genetic association data were used to
      build an interactome network model in BioGRID 3.2.99. The top 10% of this
      protein:protein JIA Interactome was used to generate a minimal essential network
      (MEN). Reactome FI Cytoscape 2.83 Plugin and the Disease Association Protein
      Protein Link Evaluator (Dapple) algorithm were used to assess the functionality
      of the biological pathways within the MEN and to statistically rank the proteins.
      JIA gene expression data were integrated with the MEN and clusters of
      functionally important proteins derived using MCODE. RESULTS: A JIA interactome
      of 2,479 proteins was built from 348 JIA associated genes. The MEN, representing
      the most functionally related components of the network, comprised of seven
      clusters, with distinct functional characteristics. Four gene expression datasets
      from peripheral blood mononuclear cells (PBMC), neutrophils and synovial fluid
      monocytes, were mapped onto the MEN and a list of genes enriched for functional
      significance identified. This analysis revealed the genes of greatest potential
      functional importance to be PTPN2 and STAT1 for oligoarticular JIA and KSR1 for
      RF-ve polyarticular JIA. Clusters of 23 and 14 related proteins were derived for
      oligoarticular and RF-ve polyarticular JIA respectively. CONCLUSIONS: This first
      report of the application of network biology to JIA, integrating genetic
      association findings and gene expression data, has prioritised protein clusters
      for functional validation and identified new pathways for targeted
      pharmacological intervention.

PMID- 24886661
TI  - Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and
      suppresses growth of HeLa tumor xenografts.
AB  - BACKGROUND: Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is
      present in many types of solid tumors. Expression of CA IX is driven
      predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain
      intracellular pH homeostasis under hypoxic conditions, resulting in acidification
      of the tumor microenvironment. Carnosine (beta-alanyl-L-histidine) is an anti
      tumorigenic agent that inhibits the proliferation of cancer cells. In this study,
      we investigated the role of CA IX in carnosine-mediated antitumor activity and
      whether the underlying mechanism involves transcriptional and translational
      modulation of HIF-1alpha and CA IX and/or altered CA IX function. METHODS: The
      effect of carnosine was studied using two-dimensional cell monolayers of several
      cell lines with endogenous CA IX expression as well as Madin Darby canine kidney
      transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa
      xenografts in nude mice. mRNA and protein expression and protein localization
      were analyzed by real-time PCR, western blot analysis, and immunofluorescence
      staining, respectively. Cell viability was measured by a flow cytometric assay.
      Expression of HIF-1alpha and CA IX in tumors was assessed by immunohistochemical
      staining. Real-time measurement of pH was performed using a sensor dish reader.
      Binding of CA IX to specific antibodies and metabolon partners was investigated
      by competitive ELISA and proximity ligation assays, respectively. RESULTS:
      Carnosine increased the expression levels of HIF-1alpha and HIF targets and
      increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated
      acidosis. Moreover, carnosine significantly inhibited the growth of three
      dimensional spheroids and tumor xenografts compared with untreated controls.
      Competitive ELISA showed that carnosine disrupted binding between CA IX and
      antibodies specific for its catalytic domain. This finding was supported by
      reduced formation of the functional metabolon of CA IX and anion exchanger 2 in
      the presence of carnosine. CONCLUSIONS: Our results indicate that interaction of
      carnosine with CA IX leads to conformational changes of CA IX and impaired
      formation of its metabolon, which in turn disrupts CA IX function. These findings
      suggest that carnosine could be a promising anticancer drug through its ability
      to attenuate the activity of CA IX.

PMID- 24886662
TI  - How informative is your kinetic model?: using resampling methods for model
      invalidation.
AB  - BACKGROUND: Kinetic models can present mechanistic descriptions of molecular
      processes within a cell. They can be used to predict the dynamics of metabolite
      production, signal transduction or transcription of genes. Although there has
      been tremendous effort in constructing kinetic models for different biological
      systems, not much effort has been put into their validation. In this study, we
      introduce the concept of resampling methods for the analysis of kinetic models
      and present a statistical model invalidation approach. RESULTS: We based our
      invalidation approach on the evaluation of a kinetic model's predictive power
      through cross validation and forecast analysis. As a reference point for this
      evaluation, we used the predictive power of an unsupervised data analysis method
      which does not make use of any biochemical knowledge, namely Smooth Principal
      Components Analysis (SPCA) on the same test sets. Through a simulations study, we
      showed that too simple mechanistic descriptions can be invalidated by using our
      SPCA-based comparative approach until high amount of noise exists in the
      experimental data. We also applied our approach on an eicosanoid production model
      developed for human and concluded that the model could not be invalidated using
      the available data despite its simplicity in the formulation of the reaction
      kinetics. Furthermore, we analysed the high osmolarity glycerol (HOG) pathway in
      yeast to question the validity of an existing model as another realistic
      demonstration of our method. CONCLUSIONS: With this study, we have successfully
      presented the potential of two resampling methods, cross validation and forecast
      analysis in the analysis of kinetic models' validity. Our approach is easy to
      grasp and to implement, applicable to any ordinary differential equation (ODE)
      type biological model and does not suffer from any computational difficulties
      which seems to be a common problem for approaches that have been proposed for
      similar purposes. Matlab files needed for invalidation using SPCA cross
      validation and our toy model in SBML format are provided at
      http://www.bdagroup.nl/content/Downloads/software/software.php.

PMID- 24886663
TI  - Synergistic white matter protection with acute-on-chronic endotoxin and
      subsequent asphyxia in preterm fetal sheep.
AB  - BACKGROUND: Perinatal asphyxia and exposure to intrauterine infection are
      associated with impaired neurodevelopment in preterm infants. Acute exposure to
      non-injurious infection and/or inflammation can either protect or sensitize the
      brain to subsequent hypoxia-ischemia. However, the effects of subacute infection
      and/or inflammation are unclear. In this study we tested the hypothesis that
      acute-on-chronic exposure to lipopolysaccharide (LPS) would exacerbate white
      matter injury after subsequent asphyxia in preterm fetal sheep. METHODS: Fetal
      sheep at 0.7 gestational age received a continuous LPS infusion at 100 ng/kg for
      24 hours, then 250 ng/kg/24 hours for 96 hours, plus 1 MUg boluses of LPS at 48,
      72, and 96 hours or the same volume of saline. Four hours after the last bolus,
      complete umbilical cord occlusion or sham occlusion was induced for 15 minutes.
      Sheep were sacrificed 10 days after the start of infusions. RESULTS: LPS exposure
      was associated with induction of microglia and astrocytes and loss of total and
      immature and mature oligodendrocytes (n = 9) compared to sham controls (n = 9).
      Umbilical cord occlusion with saline infusions was associated with induction of
      microglia, astrogliosis, and loss of immature and mature oligodendrocytes (n =
      9). LPS exposure before asphyxia (n = 8) was associated with significantly
      reduced microglial activation and astrogliosis and improved numbers of immature
      and mature oligodendrocytes compared to either LPS exposure or asphyxia alone.
      CONCLUSIONS: Contrary to our initial hypothesis, the combination of acute-on
      chronic LPS with subsequent asphyxia reduced neuroinflammation and white matter
      injury compared with either intervention alone.

PMID- 24886664
TI  - A real-time comparison between direct control, sequential pattern recognition
      control and simultaneous pattern recognition control using a Fitts' law style
      assessment procedure.
AB  - BACKGROUND: Pattern recognition (PR) based strategies for the control of
      myoelectric upper limb prostheses are generally evaluated through offline
      classification accuracy, which is an admittedly useful metric, but insufficient
      to discuss functional performance in real time. Existing functional tests are
      extensive to set up and most fail to provide a challenging, objective framework
      to assess the strategy performance in real time. METHODS: Nine able-bodied and
      two amputee subjects gave informed consent and participated in the local
      Institutional Review Board approved study. We designed a two-dimensional target
      acquisition task, based on the principles of Fitts' law for human motor control.
      Subjects were prompted to steer a cursor from the screen center of into a series
      of subsequently appearing targets of different difficulties. Three cursor control
      systems were tested, corresponding to three electromyography-based prosthetic
      control strategies: 1) amplitude-based direct control (the clinical standard of
      care), 2) sequential PR control, and 3) simultaneous PR control, allowing for a
      concurrent activation of two degrees of freedom (DOF). We computed throughput
      (bits/second), path efficiency (%), reaction time (second), and overshoot (%))
      and used general linear models to assess significant differences between the
      strategies for each metric. RESULTS: We validated the proposed methodology by
      achieving very high coefficients of determination for Fitts' law. Both PR
      strategies significantly outperformed direct control in two-DOF targets and were
      more intuitive to operate. In one-DOF targets, the simultaneous approach was the
      least precise. The direct control was efficient in one-DOF targets but cumbersome
      to operate in two-DOF targets through a switch-depended sequential cursor
      control. CONCLUSIONS: We designed a test, capable of comprehensively describing
      prosthetic control strategies in real time. When implemented on control subjects,
      the test was able to capture statistically significant differences (p < 0.05) in
      control strategies when considering throughputs, path efficiencies and reaction
      times. Of particular note, we found statistically significant (p < 0.01)
      improvements in throughputs and path efficiencies with simultaneous PR when
      compared to direct control or sequential PR. Amputees could readily achieve the
      task; however a limited number of subjects was tested and a statistical analysis
      was not performed with that population.

PMID- 24886665
TI  - Chondrosarcoma metastasis in the thyroid gland: a case report.
AB  - INTRODUCTION: Chondrosarcoma metastases in the thyroid gland are exceptional. To
      the best of our knowledge, only two cases have been previously reported in the
      literature. Here we report the third case. CASE PRESENTATION: We report the case
      of a 51-year-old Arab woman who presented in 2011 with a diaphyseal
      chondrosarcoma of her right tibia treated by surgery. In the last quarter of
      2013, she presented a hard mass in her thyroid gland with dyspnea and a right
      laryngeal paresis. She underwent a debulking surgery with tracheostomy in order
      to prevent difficulty in respiration. The final pathology revealed the diagnosis
      of a chondrosarcoma metastasis within her thyroid gland. She died several days
      later. CONCLUSIONS: Even if primary and metastatic chondrosarcomas of the thyroid
      gland are exceptional, they should be considered in the differential diagnosis of
      thyroid gland masses. The prognosis is poor but surgery may help preserve quality
      of life.

PMID- 24886666
TI  - A novel and practical cardiovascular magnetic resonance method to quantify mitral
      annular excursion and recoil applied to hypertrophic cardiomyopathy.
AB  - BACKGROUND: We have developed a novel and practical cardiovascular magnetic
      resonance (CMR) technique to evaluate left ventricular (LV) mitral annular motion
      by tracking the atrioventricular junction (AVJ). To test AVJ motion analysis as a
      metric for LV function, we compared AVJ motion variables between patients with
      hypertrophic cardiomyopathy (HCM), a group with recognized systolic and diastolic
      dysfunction, and healthy volunteers. METHODS: We retrospectively evaluated 24 HCM
      patients with normal ejection fractions (EF) and 14 healthy volunteers. Using the
      4-chamber view cine images, we tracked the longitudinal motion of the lateral and
      septal AVJ at 25 time points during the cardiac cycle. Based on AVJ displacement
      versus time, we calculated maximum AVJ displacement (MD) and velocity in early
      diastole (MVED), velocity in diastasis (VDS) and the composite index VDS/MVED.
      RESULTS: Patients with HCM showed significantly slower median lateral and septal
      AVJ recoil velocities during early diastole, but faster velocities in diastasis.
      We observed a 16-fold difference in VDS/MVED at the lateral AVJ [median 0.141,
      interquartile range (IQR) 0.073, 0.166 versus 0.009 IQR -0.006, 0.037, P <
      0.001]. Patients with HCM also demonstrated significantly less mitral annular
      excursion at both the septal and lateral AVJ. Performed offline, AVJ motion
      analysis took approximately 10 minutes per subject. CONCLUSIONS: Atrioventricular
      junction motion analysis provides a practical and novel CMR method to assess
      mitral annular motion. In this proof of concept study we found highly
      statistically significant differences in mitral annular excursion and recoil
      between HCM patients and healthy volunteers.

PMID- 24886667
TI  - Retrograde tibial nailing: a minimally invasive and biomechanically superior
      alternative to angle-stable plate osteosynthesis in distal tibia fractures.
AB  - BACKGROUND: Currently, antegrade intramedullary nailing and minimally invasive
      plate osteosynthesis (MIPO) represent the main surgical alternatives in distal
      tibial fractures. However, neither choice is optimal for all bony and soft tissue
      injuries. The Retrograde Tibial Nail (RTN) is a small-caliber prototype implant,
      which is introduced through a 2-cm-long incision at the tip of the medial
      malleolus with stab incisions sufficient for interlocking. During this project,
      we investigated the feasibility of retrograde tibial nailing in a cadaver model
      and conducted biomechanical testing. METHODS: Anatomical implantations of the RTN
      were carried out in AO/OTA 43 A1-3 fracture types in three cadaveric lower limbs.
      Biomechanical testing was conducted in an AO/OTA 43 A3 fracture model for extra
      axial compression, torsion, and destructive extra-axial compression. Sixteen
      composite tibiae were used to compare the RTN against an angle-stable plate
      osteosynthesis (Medial Distal Tibial Plate, Synthes(r)). Statistical analysis was
      performed by Student's t test. RESULTS: Retrograde intramedullary nailing is
      feasible in simple fracture types by closed manual reduction and percutaneous
      reduction forceps, while in highly comminuted fractures, the use of a large
      distractor can aid the reduction. Biomechanical testing shows a statistically
      superior stability (p < 0.001) of the RTN during non-destructive axial loading
      and torsion. Destructive extra-axial compression testing resulted in failure of
      all plate constructs, while all RTN specimens survived the maximal load of 1,200
      N. CONCLUSIONS: The prototype retrograde tibial nail meets the requirements of
      maximum soft tissue protection by a minimally invasive surgical approach with the
      ability of secure fracture fixation by multiple locking options. Retrograde
      tibial nailing with the RTN is a promising concept in the treatment of distal
      tibia fractures.

PMID- 24886668
TI  - Quality of life in rectal cancer patients after radical surgery: a survey of
      Chinese patients.
AB  - BACKGROUND: We aimed to investigate the impact of sociodemographic and clinical
      characteristics on health-related quality of life (HRQoL) in disease-free
      survivors after radical surgery for rectal cancer in a Chinese mainland
      population. METHODS: We performed a cross-sectional survey from August 2002 to
      February 2011 by use of the European Organization for Research and Treatment of
      Cancer (EORTC) QLQ-C30 and QLQ-CR38 questionnaires of 438 patients who underwent
      curative surgery for rectal cancer. Patients who were followed up for a minimum
      of 6 months, had no relevant major comorbidities and whose disease had not
      recurred were asked to complete both questionnaires. The impact of
      sociodemographic and clinical characteristics on HRQoL were compared by
      univariate and multivariate regression analyses. RESULTS: In total, 285 patients
      responded to the survey (response rate, 65.1%). Psychological-related HRQoL
      variables such as emotional function (P = 0.021) and future perspectives (P =
      0.044) were poorer for younger patients than for older patients; and
      physiological-related HRQoL was reflected by physical function (P = 0.039), which
      was poorer for older patients than for younger patients. In terms of physiologic
      function and symptoms concerning HRQoL, such as pain (P = 0.002) and insomnia (P
      = 0.018), females had lower values than males. Low education and unemployment
      were associated with a worse HRQoL. HRQoL was worse for patients with stomas
      compared to those without, especially in psychosocial areas such as role function
      (P = 0.025), social function (P <0.001) and body image (P = 0.004). Financial
      HRQoL was worse for younger patients and patients with stoma. CONCLUSIONS: HRQoL
      aspects and degrees to which they were impaired after curative surgery for rectal
      cancer were different when compared by many sociodemographic and clinical factors
      in Chinese mainland patients.

PMID- 24886670
TI  - Life-space mobility assessment in older people in Finland; measurement properties
      in winter and spring.
AB  - BACKGROUND: Life-space mobility refers to the spatial area an individual moves
      through, the frequency and need for assistance. Based on the assumption that
      measurement scale properties are context-specific, we tested the scale
      distribution, responsiveness, and reproducibility of the 15-item University of
      Alabama at Birmingham Study of Aging Life-Space Assessment in older people in
      Finland, specifically accounting for season. METHODS: Community-dwelling older
      men and women in central Finland aged 75-90 years were interviewed to determine
      life-space mobility (score range 0-120). Baseline (January-June 2012) and one
      year follow-up data (January-June 2013; n = 806) from the cohort study "Life
      space mobility in old age" were used to investigate the scale distribution and
      responsiveness over a period of one year. In addition, with a sub-sample in
      conjunction with the one-year follow-up, we collected data to study the two-week
      test-retest reproducibility (n = 18 winter and n = 21 spring 2013). RESULTS: The
      median life-space mobility score at baseline was 64. The median change in score
      over the one-year follow-up was zero. However, participants reporting a decline
      in health (repeated measures ANOVA p = .016) or mobility (p = .002) status
      demonstrated a significantly larger decrease in life-space mobility score than
      those reporting no or positive changes over the year. The two-week intra-class
      correlation (ICC) coefficient was .72. Lower ICC was found in the winter than in
      the spring sample and for items that represent higher life-space levels.
      CONCLUSIONS: The test-retest reproducibility of the Life-Space Assessment was
      fair but somewhat compromised in the winter. Mobility of older people at the life
      space levels of "town" and "beyond town" may be more variable. Life-space
      mobility was responsive to change, regardless of season. Further study is
      warranted to obtain insight in the factors contributing to seasonal effects.

PMID- 24886669
TI  - Survivin family proteins as novel molecular determinants of doxorubicin
      resistance in organotypic human breast tumors.
AB  - INTRODUCTION: The molecular determinants of breast cancer resistance to first
      line anthracycline-containing chemotherapy are unknown. METHODS: We examined the
      response to doxorubicin of organotypic cultures of primary human breast tumors ex
      vivo with respect to cell proliferation, DNA damage and modulation of apoptosis.
      Samples were analyzed for genome-wide modulation of cell death pathways,
      differential activation of p53, and the role of survivin family molecules in drug
      resistance. Rational drug combination regimens were explored by high-throughput
      screening, and validated in model breast cancer cell types. RESULTS: Doxorubicin
      treatment segregated organotypic human breast tumors into distinct Responder or
      Non Responder groups, characterized by differential proliferative index,
      stabilization of p53, and induction of apoptosis. Conversely, tumor histotype,
      hormone receptor or human epidermal growth factor receptor-2 (HER2) status did
      not influence chemotherapy sensitivity. Global analysis of cell death pathways
      identified survivin and its alternatively spliced form, survivin-DeltaEx3 as
      uniquely overexpressed in Non Responder breast tumors. Forced expression of
      survivin-DeltaEx3 preserved cell viability and prevented doxorubicin-induced
      apoptosis in breast cancer cell types. High-throughput pharmacologic targeting of
      survivin family proteins with a small-molecule survivin suppressant currently in
      the clinic (YM155) selectively potentiated the effect of doxorubicin, but not
      other chemotherapeutics in breast cancer cell types, and induced tumor cell
      apoptosis. CONCLUSIONS: Survivin family proteins are novel effectors of
      doxorubicin resistance in chemotherapy-naive breast cancer. The incorporation of
      survivin antagonist(s) in anthracycline-containing regimens may have improved
      clinical activity in these patients.

PMID- 24886671
TI  - Could baseline health-related quality of life (QoL) predict overall survival in
      metastatic colorectal cancer? The results of the GERCOR OPTIMOX 1 study.
AB  - BACKGROUND: Health-related quality of life (QoL) has prognostic value in many
      cancers. A recent study found that the performance of prognostic systems for
      metastatic colorectal cancer (mCRC) were improvable. We evaluated the independent
      prognostic value of QoL for overall survival (OS) and its ability to improve two
      prognostic systems'performance (Kohne and GERCOR models) for patients with mCRC.
      METHODS: The EQ-5D questionnaire was self-completed before randomization in the
      OPTIMOX1, a phase III trial comparing two strategies of FOLFOX chemotherapy which
      included 620 previously untreated mCRC patients recruited from January 2000 to
      June 2002 from 56 institutions in five countries. The improvement in models'
      performance (after addition of QoL) was studied with Harrell's C-index and the
      net reclassification improvement. RESULTS: Of the 620 patients, 249 (40%)
      completed QoL datasets. The Kohne model could be improved by LDH, mobility and
      pain/discomfort; the C-index rose from 0.54 to 0.67. The associated NRI for 12
      month death was 0.23 [0.05; 0.46]. Mobility and pain/discomfort could be added to
      the GERCOR model: the C-index varied from 0.63 to 0.68. The NRI for 12 months
      death was 0.35 [0.12; 0.44]. CONCLUSIONS: Mobility and pain dimensions of EQ5D
      are independent prognostic factors and could be useful for staging and treatment
      assignment of mCRC patients. Presented at the 2011 ASCO Annual Meeting (#3632).

PMID- 24886672
TI  - Samba virus: a novel mimivirus from a giant rain forest, the Brazilian Amazon.
AB  - BACKGROUND: The identification of novel giant viruses from the nucleocytoplasmic
      large DNA viruses group and their virophages has increased in the last decade and
      has helped to shed light on viral evolution. This study describe the discovery,
      isolation and characterization of Samba virus (SMBV), a novel giant virus
      belonging to the Mimivirus genus, which was isolated from the Negro River in the
      Brazilian Amazon. We also report the isolation of an SMBV-associated virophage
      named Rio Negro (RNV), which is the first Mimivirus virophage to be isolated in
      the Americas. METHODS/RESULTS: Based on a phylogenetic analysis, SMBV belongs to
      group A of the putative Megavirales order, possibly a new virus related to
      Acanthamoeba polyphaga mimivirus (APMV). SMBV is the largest virus isolated in
      Brazil, with an average particle diameter about 574 nm. The SMBV genome contains
      938 ORFs, of which nine are ORFans. The 1,213.6 kb SMBV genome is one of the
      largest genome of any group A Mimivirus described to date. Electron microscopy
      showed RNV particle accumulation near SMBV and APMV factories resulting in the
      production of defective SMBV and APMV particles and decreasing the infectivity of
      these two viruses by several logs. CONCLUSION: This discovery expands our
      knowledge of Mimiviridae evolution and ecology.

PMID- 24886673
TI  - Stereopsis impairment is associated with decreased color perception and worse
      motor performance in Parkinson's disease.
AB  - BACKGROUND: We conducted this study is to investigate the correlation between
      stereopsis dysfunction and color perception, as well as whether stereopsis
      impairment is associated with motor dysfunction in patients with Parkinson's
      disease (PD). METHOD: Our present study included 45 PD patients and 50 non-PD
      control patients attending the Movement Disorder Center at Xuanwu Hospital
      Capital Medical University in Beijing from July 2011 to November 2011. Neurologic
      evaluations and visual function assessments were conducted, and the results
      between two groups of patients were compared. RESULTS: We found that the total
      error scores (TESs) and partial error scores (PESs) for red, green, blue and
      purple were all significantly higher in PD patients than in control patients. The
      limited grade on the FLY Stereo Acuity Test with LEA Symbols was significantly
      lower in PD patients than in control patients (P = 0.0001), whereas the
      percentage of abnormal stereopsis in PD patients was significantly higher than in
      control patients (42.2% vs. 12%; P = 0.001). Multiple linear regression analysis
      showed that PD patients with higher Hoehn and Yahr Scale stage, and those with
      decreased stereopsis had higher Unified Parkinson's Disease Rating Scale (UPDRS)
      motor scores and worse motor function. Furthermore, our study demonstrates that
      the UPDRS motor scores and total average number of the Purdue Pegboard Test
      scores of PD patients were significantly improved when they had taken their
      medications, and the TESs and PESs for green were lower in when they were off
      their medications. CONCLUSION: Our results provide more information on the
      underlying mechanisms of vision, motor and stereopsis impairments in PD patients.

PMID- 24886674
TI  - Efficacy and adverse events of high-frequency oscillatory ventilation in adult
      patients with acute respiratory distress syndrome: a meta-analysis.
AB  - INTRODUCTION: Theoretically, high-frequency oscillatory ventilation (HFOV)
      achieves all goals of a lung-protective ventilatory mode and seems ideal for the
      treatment of adult patients with acute respiratory distress syndrome (ARDS).
      However, its effects on mortality and adverse clinical outcomes remain uncertain
      given the paucity of high-quality studies in this area. This meta-analysis was
      performed to evaluate the efficacy and adverse events of HFOV in adults with
      ARDS. METHODS: We searched PubMed, EMBASE and Cochrane Central Register of
      Controlled Trials through February 2014 to retrieve randomized controlled trials
      of HFOV in adult ARDS patients. Two independent reviewers extracted data on study
      methods, clinical and physiological outcomes and adverse events. The primary
      outcome was 30-day or hospital mortality. Risk of bias was evaluated with the
      Cochrane Collaboration's tool. Mortality, oxygenation and adverse effects of HFOV
      were compared to those of conventional mechanical ventilation. A random-effects
      model was applied for meta-analysis. RESULTS: A total of five trials randomly
      assigning 1,580 patients met inclusion criteria. Pooled data showed that HFOV
      significantly improved oxygenation on day one of therapy (four studies; 24%
      higher; 95% confidence interval (CI) 11 to 40%; P <0.01). However, HFOV did not
      reduce mortality risk (five studies; risk ratio (RR) 1.04; 95% CI 0.83 to 1.31; P
      = 0.71) and two early terminated studies suggested a harmful effect of HFOV in
      ARDS (two studies; RR 1.33; 95% CI 1.09 to 1.62; P <0.01). Safety profiles showed
      that HFOV was associated with a trend toward increased risk of barotrauma (five
      studies; RR 1.19; 95% CI 0.83 to 1.72; P = 0.34) and unfavorable hemodynamics
      (five studies; RR 1.16; 95% CI 0.97 to 1.39; P = 0.12). CONCLUSIONS: HFOV
      improved oxygenation in adult patients with ARDS; however, it did not confer a
      survival benefit and might cause harm in the era of lung-protective ventilation
      strategy. The evidence suggests that HFOV should not be a routine practice in
      ARDS and further studies specifically selecting patients for this ventilator mode
      should be pursued.

PMID- 24886675
TI  - Assessment of a novel multi-array normalization method based on spike-in control
      probes suitable for microRNA datasets with global decreases in expression.
AB  - BACKGROUND: High-quality expression data are required to investigate the
      biological effects of microRNAs (miRNAs). The goal of this study was, first, to
      assess the quality of miRNA expression data based on microarray technologies and,
      second, to consolidate it by applying a novel normalization method. Indeed,
      because of significant differences in platform designs, miRNA raw data cannot be
      normalized blindly with standard methods developed for gene expression. This
      fundamental observation motivated the development of a novel multi-array
      normalization method based on controllable assumptions, which uses the spike-in
      control probes to adjust the measured intensities across arrays. RESULTS: Raw
      expression data were obtained with the Exiqon dual-channel miRCURY LNATM platform
      in the "common reference design" and processed as "pseudo-single-channel". They
      were used to apply several quality metrics based on the coefficient of variation
      and to test the novel spike-in controls based normalization method. Most of the
      considerations presented here could be applied to raw data obtained with other
      platforms. To assess the normalization method, it was compared with 13 other
      available approaches from both data quality and biological outcome perspectives.
      The results showed that the novel multi-array normalization method reduced the
      data variability in the most consistent way. Further, the reliability of the
      obtained differential expression values was confirmed based on a quantitative
      reverse transcription-polymerase chain reaction experiment performed for a subset
      of miRNAs. The results reported here support the applicability of the novel
      normalization method, in particular to datasets that display global decreases in
      miRNA expression similarly to the cigarette smoke-exposed mouse lung dataset
      considered in this study. CONCLUSIONS: Quality metrics to assess between-array
      variability were used to confirm that the novel spike-in controls based
      normalization method provided high-quality miRNA expression data suitable for
      reliable downstream analysis. The multi-array miRNA raw data normalization method
      was implemented in an R software package called ExiMiR and deposited in the
      Bioconductor repository.

PMID- 24886676
TI  - Exploring the feasibility and acceptability of couple-based psychosexual support
      following prostate cancer surgery: study protocol for a pilot randomised
      controlled trial.
AB  - BACKGROUND: Men who undergo surgery for prostate cancer frequently experience
      significant side-effects including urinary and sexual dysfunction. These
      difficulties can lead to anxiety, depression and reduced quality of life. Many
      partners also experience psychological distress. An additional impact can be on
      the couple relationship, with changes to intimacy, and unmet psychosexual
      supportive needs in relation to sexual recovery and rehabilitation. The aim of
      this exploratory randomised controlled trial pilot study is to determine the
      feasibility and acceptability of a novel family-relational-psychosexual
      intervention to support intimacy and reduce distress among couples following
      prostate cancer surgery and to estimate the efficacy of this intervention.
      METHODS/DESIGN: The intervention will comprise six sessions of psychosexual and
      relationship support delivered by experienced couple-support practitioners.
      Specialist training in delivering the intervention will be provided to
      practitioners and they will be guided by a detailed treatment manual based on
      systemic principles. Sixty-eight couples will be randomised to receive either the
      intervention or standard care (comprising usual follow-up hospital appointments).
      A pre-test, post-test design will be used to test the feasibility of the
      intervention (baseline, end of intervention and six-month follow-up) and its
      acceptability to couples and healthcare professionals (qualitative interviews).
      Both individual and relational outcome measures will assess sexual functioning,
      anxiety and depression, couple relationship, use of health services and erectile
      dysfunction medication/technologies. An economic analysis will estimate
      population costs of the intervention, compared to usual care, using simple
      modelling to evaluate the affordability of the intervention. DISCUSSION: Given
      the increasing incidence and survival of post-operative men with prostate cancer,
      it is timely and appropriate to determine the feasibility of a definitive trial
      through a pilot randomised controlled trial of a family-relational-psychosexual
      intervention for couples. The study will provide evidence about the components of
      a couple-based intervention, its acceptability to patients and healthcare
      professionals, and its influence on sexual and relational functioning. Data from
      this study will be used to calculate sample sizes required for any definitive
      trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01842438.Registration date: 24 April 2013; Randomisation of first patient: 13
      May 2013.

PMID- 24886677
TI  - Higher Caspase-like activity in symptomatic isolates of Blastocystis spp.
AB  - BACKGROUND: Biochemical evidence of a caspase-like execution pathway has been
      demonstrated in a variety of protozoan parasites, including Blastocystis spp. The
      distinct differences in the phenotypic characterization reported previously have
      prompted us to compare the rate of apoptosis in Blastocystis spp. isolated from
      individuals who were symptomatic and asymptomatic. In the current study, we
      analysed the caspase activation involved in PCD mediated by a cytotoxic drug,
      (metronidazole) in both symptomatic & asymptomatic isolates. METHODS: Apoptosis
      was induced in Blastocystis spp. by treating cultures of symptomatic and
      asymptomatic isolates of 3 sub-types namely 1, 3 and 5 with two different
      concentrations, 0.1 and 0.0001 mg/ml of metronidazole (with and without pre
      treatment with a pan-caspase inhibitor, zVAD.fmk). The experiment was repeated to
      assess the number of apoptotic cells in all the isolates of both conditions.
      RESULTS: Symptomatic isolates of subtype 3 (without pre-treatment with a pan
      caspase inhibitor, zVAD.fmk) showed high fluorescence intensity for active
      caspase-like proteases [0.0001 mg/ml, 88% (p < 0.001) at 0.1 mg/ml, 70% (p <
      0.001)] at the 72nd hour in vitro culture in comparison with asymptomatic
      isolates [0.0001 mg/ml, 65%, at 0.1 mg/ml, 55%]. The number of apoptotic cells
      was higher [0.0001 mg/ml, 89% (p < 0.001) and at 0.1 mg/ml, 70% (p < 0.001)] at
      the 72nd hour of in vitro culture in comparison with asymptomatic isolates
      [0.0001 mg/ml, 66% (p < 0.001) and at 0.1 mg/ml, 45% (p < 0.01)]. Cells treated
      with metronidazole in the presence of zVAD.fmk showed less than 10% caspase
      activation. CONCLUSION: The high number of symptomatic cells expressing active
      caspase-like proteases and becoming apoptotic compared to asymptomatic cells
      clearly demonstrates that the response to metronidazole treatment is isolate
      dependent. Hence this justifies the conflicting reports on the curative success
      rates when treated with this drug. The study has also created a need to identify
      apoptosis effectors in Blastocystis spp of different isolates especially as it
      was shown that apoptosis was sub-typed related. These findings can be exploited
      for the development of diagnostic markers and novel therapeutic drugs to enhance
      the effectiveness of the diagnosis and treatment of the patients infected with
      Blastocystis spp.

PMID- 24886678
TI  - Synergistic effects of combined platelet-activating factor receptor and epidermal
      growth factor receptor targeting in ovarian cancer cells.
AB  - BACKGROUND: Genetic alterations, including the overexpression of epidermal growth
      factor receptor (EGFR), play a crucial role in ovarian carcinogenesis. To date,
      EGFR targeting has shown limited antitumor effects in ovarian cancer when
      administered as monotherapy. We previously identified platelet-activating factor
      receptor (PAFR) as being overexpressed in ovarian cancer and found that its
      ligand PAF evoked EGFR phosphorylation. To determine whether PAFR targeting can
      enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of
      a PAFR antagonist (WEB2086) in conjunction with an EGFR inhibitor (AG1478).
      METHODS: The expression of EGFR and PAFR in CAOV-3 and SKOV-3 ovarian cancer cell
      lines was measured by Western blot and immunocytochemistry. Synergy was
      determined using isobologram analysis. The effects of combined PAFR and EGFR
      targeting on both cells were assessed by using CCK-8, transwell, flow cytometry,
      western blot analysis. In vivo studies were conducted using CAOV-3 cells
      xenografted in nu/nu mice. RESULTS: Treatment with combination WEB2086 and AG1478
      resulted in significantly greater inhibition of proliferation and invasion
      compared to either drug alone. When examining equipotent combinations of WEB2086
      and AG1478 to determine potential synergy, a combination index (CI) of 0.49 was
      identified for CAOV-3 cells and a CI of 0.58 for SKOV-3 cells indicating synergy.
      This co-inhibition induced significantly more apoptosis and arrested the cells at
      G0/G1 phase in both cell lines. The activation of PAFR and/or EGFR induced
      phosphorylation of the mTOR, AKT, and MAPK pathways. Combined PAFR and EGFR
      targeting synergistically diminished the expression of PAFR and EGFR
      phosphorylation and downstream signaling. In vivo studies further verified the
      antitumor effects of combined PAFR and EGFR targeting in a CAOV-3 xenograft
      model. CONCLUSIONS: These results suggest that WEB2086 and AG1478 are synergistic
      in ovarian cancer cells with high expression of both PAFR and EGFR. The presented
      approach may have important therapeutic implications in the treatment of ovarian
      cancer patients.

PMID- 24886679
TI  - In vitro and ex-vivo cellular antioxidant protection and cognitive enhancing
      effects of an extract of Polygonum minus Huds (LineminusTM) demonstrated in a
      Barnes Maze animal model for memory and learning.
AB  - BACKGROUND: Polygonum minus Huds.is a culinary flavouring that is common in South
      East Asian cuisine and as a remedy for diverse maladies ranging from indigestion
      to poor eyesight. The leaves of this herb have been reported to be high in
      antioxidants. Flavonoids which have been associated with memory, cognition and
      protection against neurodegeneration were found in P. minus. METHOD: This study
      examined a P. minus aqueous extract (LineminusTM) for its antioxidant activity
      using the Oxygen Radical Absorbance Capacity (ORAC) assay, the ex vivo Cellular
      Antioxidant Protection of erythrocytes (CAP-e) assays and for potential
      anticholinesterase activity in vitro. Cognitive function and learning of
      LineminusTM was evaluated using scopolamine induced cognition deficits in a
      Barnes maze, rodent model of cognition. RESULTS: The extract displayed in vitro
      antioxidant activity with a total ORAC value of 16,964 MUmole TE/gram. Cellular
      antioxidant protection from free radical damage using the CAP-e assay, with an
      IC50 of 0.58 g/L for inhibition of cellular oxidative damage, was observed. The
      extract inhibited cholinesterase activity with an IC50 of 0.04 mg/ml with a
      maximum inhibition of 68%. In a rodent model of cognition using scopolamine
      induced cognition deficits in the Barnes maze, the extract attenuated scopolamine
      induced disruptions in learning at the higher dose of 100 mg/kg. CONCLUSION:
      These data shows that P. minus possesses antioxidant and anticholinesterase
      activity and demonstrated enhanced cognition in vivo. The data suggest
      neuroprotective properties of the extract.

PMID- 24886680
TI  - Accelerated partial breast irradiation in the elderly: 5-year results of high
      dose rate multi-catheter brachytherapy.
AB  - OBJECTIVE: To evaluate clinical outcome after accelerated partial breast
      irradiation (APBI) in the elderly after high-dose-rate interstitial multi
      catheter brachytherapy (HIBT). METHODS AND MATERIALS: Between 2005 and 2013, 70
      patients underwent APBI using HIBT. Catheter implant was performed intra or post
      operatively (referred patients) after lumpectomy and axillary sentinel lymph node
      dissection. Once the pathological results confirmed the indication of APBI,
      planification CT-scan was performed to deliver 34 Gy/10f/5d or 32 Gy/8f/4d. Dose
      volume adaptation was manually achieved (graphical optimization). Dosimetric
      results and clinical outcome were retrospectively analyzed. Physician cosmetic
      evaluation was reported. RESULTS: With a median follow-up of 60.9 months [4.6 -
      90.1], median age was 80.7 years [62 - 93.1]. Regarding APBI ASTRO criteria,
      61.4%, 18.6% and 20% were classified as suitable, cautionary and non-suitable
      respectively. Axillary sentinel lymph node dissection was performed in 94.3%; 8
      pts (11.5%) presented an axillary involvement. A median dose of 34 Gy [32 - 35]
      in 8 to 10 fractions was delivered. Median CTV was 75.2 cc [16.9 - 210], median
      D90 EQD2 was 43.3 Gy [35 - 72.6] and median DHI was 0.54 [0.19 - 0.74]. One
      patient experienced ipsilateral recurrence (5-year local free recurrence rate:
      97.6%. Five-year specific and overall survival rates were 97.9% and 93.2%
      respectively. Thirty-four patients (48%) presented 47 late complications
      classified grade 1 (80.8%) and grade 2 (19.2%) with no grade >= 3. Cosmetic
      results were considered excellent/good for 67 pts (95.7%). CONCLUSION: APBI using
      HIBT and respecting strict rules of implantation and planification, represents a
      smart alternative between no post-operative irradiation and whole breast
      irradiation delivered over 6 consecutive weeks.

PMID- 24886682
TI  - Prevalence and factors associated with vitamin A deficiency in children and
      adolescents.
AB  - OBJECTIVE: To identify the prevalence and factors associated with vitamin A
      deficiency (VAD) in children and adolescents. METHODS: This was a cross-sectional
      study involving 546 schoolchildren, aged between 7 and 14 years, of both genders,
      enrolled in public elementary schools. Blood was collected for measurement of
      serum retinol. The retinol concentration in the samples was determined by high
      performance liquid chromatography (HPLC). Data were collected on anthropometrics,
      dietary, demographic, and socioeconomic factors. Polytomous logistic regression
      was used to evaluate the associations of interest. RESULTS: Approximately 27.5%
      of the students had retinol values<30 MUg/dL. The multivariate analysis showed,
      after the appropriate adjustments, a positive and statistically significant
      association of moderate/severe VAD (OR=2.19; 95% CI 1.17 to 4.10) and marginal
      VAD (OR=2.34; 95% CI 1.47 to 3.73) with age<10 years. There was also association
      of VAD moderate/severe (OR=2.01; 95% CI 1.01 to 5.05) and borderline VAD
      (OR=2.14; 95% CI: 1.08 to 4.21) with the anthropometric status of underweight.
      Lower intake of retinol was detected among those with severe VAD. CONCLUSION: VAD
      is a health concern among children and adolescents. Lower weight and younger
      schoolchildren had greater vulnerability to VAD.

PMID- 24886681
TI  - Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV
      positive patients with end-stage liver disease.
AB  - INTRODUCTION: We have assessed the utility of autologous mesenchymal stem cell
      (MSC) peripheral vein infusion as a possible therapeutic modality for patients
      with end-stage liver diseases. METHODS: Forty patients with post-hepatitis C
      virus (HCV) end-stage liver disease were randomized into two groups: Group 1
      (GI): 20 patients who received granulocyte colony-stimulating factor (G-CSF) for
      5 days followed by autologous MSCs peripheral-vein infusion and group 2 (GII): 20
      patients who received regular liver-supportive treatment only (control group).
      RESULTS: In MSC-infused patients (GI), 54% showed near normalization of liver
      enzymes and improvement in liver synthetic function. Significant changes were
      reported in albumin (P = 0.000), bilirubin (P = 0.002), increased international
      normalized ratio (INR) (P = 0.017), prothrombin concentration (P = 0.029) and
      alanine transaminase (ALT) levels (P = 0.029), with stabilization of clinical and
      biochemical status in 13% of cases. None of the patients in GII showed any
      significant improvement. Hepatic fibrosis was assessed in GI by detection of
      procollagen IIIC peptide level (PIIICP) and procollagen III N peptide level
      (PIIINP). The pretreatment values of s-PIIICP and s-PIIINP were 9.4 +/- 4.2 and
      440 +/- 189, respectively, with a decrease to 8.1 +/- 2.6 and 388 +/- 102,
      respectively, 3 months after MSC therapy. However, the difference was
      statistically nonsignificant (P = 0.7). A significant correlation coefficient was
      reported after 3 months between the s-PIIINP and prothrombin concentration (P = 
      0.5) and between s-PIIICP and ascites (P = 0.550). CONCLUSIONS: First, autologous
      MSC infusion into a peripheral vein is as effective as the previously reported
      intrahepatic infusion. Second, MSCs have a supportive role in the treatment of
      end-stage liver disease, with satisfactory tolerability and beneficial effects on
      liver synthetic functions and hepatic fibrosis. Third, IV infusion of MSCs after
      G-CSF mobilization improves s-albumin within the first 2 weeks and prothrombin
      concentration and alanine Taransaminase after 1 month. According to the data from
      this current study and those previously reported by our group, we recommend
      further studies on patients' infusion with pure CD133 and CD34 followed by IV
      infusion of in vitro-differentiated MSCs within 1 week and another infusion after
      3 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT01729221. Registered 17
      November 2012.

PMID- 24886687
TI  - Development of an assay to simultaneously measure orotic acid, amino acids, and
      acylcarnitines in dried blood spots.
AB  - BACKGROUND: Orotic aciduria in the presence of hyperammonemia is a key indicator
      for a defect in the urea cycle, specifically ornithine transcarbamylase (OTC)
      deficiency. Current newborn screening (NBS) protocols can detect several defects
      of the urea cycle, but screening for OTC deficiency remains a challenge due to
      the lack of a suitable assay. The purpose of this study was to develop a high
      throughput assay to measure orotic acid in dried blood spot (DBS) specimens as an
      indicator for urea cycle dysfunction, which can be readily incorporated into
      routine NBS. METHODS: Orotic acid was extracted from DBS punches and analyzed
      using flow-injection analysis tandem mass spectrometry (FIA-MS/MS) with negative
      mode ionization, requiring <2 min/sample run time. This method was then
      multiplexed into a conventional newborn screening assay for analysis of amino
      acids, acylcarnitines, and orotic acid. RESULTS: We describe 2 assays which can
      quantify orotic acid in DBS: a stand-alone method and a combined method for
      analysis of orotic acid, amino acids, and acylcarnitines. Both methods
      demonstrated orotic acid recovery of 75-85% at multiple levels of enrichment.
      Precision was also comparable to traditional FIA-MS/MS methods. Analysis of
      residual presumptively normal NBS specimens demonstrated a 5:1 signal to noise
      ratio and the average concentration of orotic acid was approximately 1.2 MUmol/l.
      The concentration of amino acids and acylcarnitines as measured by the combined
      method showed no significant differences when compared to the conventional
      newborn screening assay. In addition, retrospective analysis of confirmed
      patients and presumptively normal newborn screening specimens suggests potential
      for the methods to identify patients with OTC deficiency, as well as other urea
      cycle defects. CONCLUSION: The assays described here quantify orotic acid in DBS
      using a simple extraction and FIA-MS/MS analysis procedures that can be
      implemented into current NBS protocols.

PMID- 24886683
TI  - MIDSHIPS: multicentre intervention designed for self-harm using interpersonal
      problem-solving: protocol for a randomised controlled feasibility study.
AB  - BACKGROUND: Around 150,000 people each year attend hospitals in England due to
      self-harm, many of them more than once. Over 5,000 people die by suicide each
      year in the UK, a quarter of them having attended hospital in the previous year
      because of self-harm. Self-harm is a major identifiable risk factor for suicide.
      People receive variable care at hospital; many are not assessed for their
      psychological needs and little psychological therapy is offered. Despite its
      frequent occurrence, we have no clear research evidence about how to reduce the
      repetition of self-harm. Some people who have self-harmed show less active ways
      of solving problems, and brief problem-solving therapies are considered the most
      promising psychological treatments. METHODS/DESIGN: This is a pragmatic,
      individually randomised, controlled, feasibility study comparing interpersonal
      problem-solving therapy plus treatment-as-usual with treatment-as-usual alone,
      for adults attending a general hospital following self-harm. A total of 60
      participants will be randomised equally between the treatment arms, which will be
      balanced with respect to the type of most recent self-harm event, number of
      previous self-harm events, gender and age. Feasibility objectives are as follows:
      a) To establish and field test procedures for implementing the problem-solving
      intervention; b) To determine the feasibility and best method of participant
      recruitment and follow up; c) To assess therapeutic delivery; d) To assess the
      feasibility of obtaining the definitive trial's primary and secondary outcomes;
      e) To assess the perceived burden and acceptability of obtaining the trial's self
      reported outcome data; f) To inform the sample size calculation for the
      definitive trial. DISCUSSION: The results of this feasibility study will be used
      to determine the appropriateness of proceeding to a definitive trial and will
      allow us to design an achievable trial of interpersonal problem-solving therapy
      for adults who self-harm. TRIAL REGISTRATION: Current Controlled Trials
      (ISRCTN54036115).

PMID- 24886686
TI  - Scaling up antiretroviral treatment and improving patient retention in care:
      lessons from Ethiopia, 2005-2013.
AB  - BACKGROUND: Antiretroviral treatment (ART) was provided to more than nine million
      people by the end of 2012. Although ART programs in resource-limited settings
      have expanded treatment, inadequate retention in care has been a challenge.
      Ethiopia has been scaling up ART and improving retention (defined as continuous
      engagement of patients in care) in care. We aimed to analyze the ART program in
      Ethiopia. METHODS: A mix of quantitative and qualitative methods was used.
      Routine ART program data was used to study ART scale up and patient retention in
      care. In-depth interviews and focus group discussions were conducted with program
      managers. RESULTS: The number of people receiving ART in Ethiopia increased from
      less than 9,000 in 2005 to more than 439, 000 in 2013. Initially, the public
      health approach, health system strengthening, community mobilization and
      provision of care and support services allowed scaling up of ART services. While
      ART was being scaled up, retention was recognized to be insufficient. To improve
      retention, a second wave of interventions, related to programmatic, structural,
      socio-cultural, and patient information systems, have been implemented. Retention
      rate increased from 77% in 2004/5 to 92% in 2012/13. CONCLUSION: Ethiopia has
      been able to scale up ART and improve retention in care in spite of its limited
      resources. This has been possible due to interventions by the ART program,
      supported by health systems strengthening, community-based organizations and the
      communities themselves. ART programs in resource-limited settings need to put in
      place similar measures to scale up ART and retain patients in care.

PMID- 24886688
TI  - Antiviral defense in shrimp: from innate immunity to viral infection.
AB  - The culture of penaeid shrimp is rapidly developing as a major business endeavor
      worldwide. However, viral diseases have caused huge economic loss in penaeid
      shrimp culture industries. Knowledge of shrimp innate immunity and antiviral
      responses has made important progress in recent years, allowing the design of
      better strategies for the prevention and control of shrimp diseases. In this
      study, we have updated information on shrimp antiviral immunity and interactions
      between shrimp hosts and viral pathogens. Current knowledge and recent progress
      in immune signaling pathways (e.g., Toll/IMD-NF-kappaB and JAK-STAT signaling
      pathways), RNAi, phagocytosis, and apoptosis in shrimp antiviral immunity are
      discussed. The mechanism of viral infection in shrimp hosts and the interactions
      between viruses and shrimp innate immune systems are also analyzed. 

PMID- 24886689
TI  - Helminths and malaria co-infections are associated with elevated serum IgE.
AB  - BACKGROUND: Both helminth and malaria infections result in a highly polarized
      immune response characterized by IgE production. This study aimed to investigate
      the total serum IgE profile in vivo as a measure of Th2 immune response in
      malaria patients with and without helminth co-infection. METHODS: A cross
      sectional observational study composed of microscopically confirmed malaria
      positive (N=197) and malaria negative (N=216) apparently healthy controls with
      and without helminth infection was conducted at Wondo Genet Health Center,
      Southern Ethiopia. A pre-designed structured format was utilized to collect socio
      demographic and clinical data of the subjects. Detection and quantification of
      helminths, malaria parasites and determination of serum IgE levels were carried
      out following standard procedures. RESULTS: Irrespective of helminth infection,
      individuals infected by malaria showed significantly high levels of serum IgE
      compared with malaria free apparently healthy controls (with and without helminth
      infections). Moreover, malaria patients co-infected with intestinal helminths
      showed high level of serum IgE compared with those malaria patients without
      intestinal helminths (2198 IU/ml versus 1668 IU/ml). A strong statistically
      significant association was observed between malaria parasite density and
      elevated serum IgE levels (2047 IU/ml versus 1778 IU/ml; P=0.001) with high and
      low parasitaemia (parasite density >50,000 parasite/MUl of blood), respectively.
      Likewise, helminth egg loads were significantly associated with elevated serum
      IgE levels (P=0.003). CONCLUSIONS: The elevated serum IgE response in malaria
      patients irrespective of helminth infection and its correlation with malaria
      parasite density and helminth egg intensity support that malaria infection is
      also a strong driver of IgE production as compared to helminths.

PMID- 24886690
TI  - Block of T-type calcium channels by protoxins I and II.
AB  - BACKGROUND: Low-voltage-activated (T-type) calcium channels play a crucial role
      in a number of physiological processes, including neuronal and cardiac pacemaker
      activity and nociception. Therefore, finding specific modulators and/or blockers
      of T-type channels has become an important field of drug discovery. One
      characteristic of T-type calcium channels is that they share several structural
      similarities with voltage-gated sodium channels (VGSCs). We therefore
      hypothesized that binding sites for certain sodium channel blocking peptide
      toxins may be present in T-type calcium channels. FINDINGS: The sodium channel
      blocker ProTx I tonically blocked native and transiently expressed T-type
      channels in the sub- to low micro molar range with at least a ten-fold
      selectivity for the T-type calcium channel hCav3.1 over hCav3.3, and more than
      one hundred fold selectivity over hCav3.2. Using chimeras of hCav3.1 and hCav3.3,
      we determined that the domain IV region of hCav3.1 is a major determinant of
      toxin affinity, with a minor contribution from domain II. Further analysis
      revealed several residues in a highly conserved region between T-type and sodium
      channels that may correspond to toxin binding sites. Mutagenesis of several of
      these residues on an individual basis, however, did not alter the blocking
      effects of the toxin. ProTx II on the other hand preferentially blocked hCav3.2
      and significantly shifted the steady state inactivation of this channel.
      CONCLUSIONS: ProTx I blocks hCav3.1 both selectively and with high affinity.
      Domain IV appears to play a major role in this selectivity with some contribution
      from domain II. Given the structural similarities between sodium and T-type
      calcium channels and the apparent conservation in toxin binding sites, these data
      could provide insights into the development and synthesis of novel T-type channel
      antagonists.

PMID- 24886691
TI  - Quantification of in situ granulation-induced changes in pre-compression,
      solubility, dose distribution and intrinsic in vitro release characteristics of
      ibuprofen-cationic dextran conjugate crystanules.
AB  - The direct effect of intermolecular association between ibuprofen and
      diethylaminoethyl dextran (Ddex) and the novel 'melt-in situ granulation
      crystallization' technique on the solubility, dose distribution, in vitro
      dissolution kinetics and pre-compression characteristics of the ibuprofen-Ddex
      conjugate crystanules have been investigated using various mathematical equations
      and statistical moments. The research intention was to elucidate the mechanisms
      of ibuprofen solubilization, densification and release from the conjugate
      crystanules as well as its dose distribution in order to provide fundamental
      knowledge on important physicochemical, thermodynamic and system-specific
      parameters which are key indices for the optimization of drug-polymer conjugate
      design for the delivery of poorly soluble drugs. The process of melt-in situ
      granulation-crystallization reduced the solubility slightly compared with pure
      ibuprofen, however, the ibuprofen-Ddex conjugate crystanules exhibited increased
      ibuprofen solubility to a maximum of 2.47*10(-1) mM (at 1.25*10(-4) mM Ddex) and
      8.72*10(-1) mM (at 6.25*10(-4) mM Ddex) at 25 and 37  degrees C, respectively.
      Beyond these concentrations of Ddex ibuprofen solubility decreased steadily due
      to stronger bond strength of the conjugate crystanules. The enthalpy-entropy
      compensation plot suggests a dominant entropy-driven mechanism of solubilization.
      In the same vein, the addition of Ddex increased the rate and extent of in vitro
      ibuprofen release from the conjugate crystanule to 100% within 168 h at Ddex
      concentration of 1.56*10(-4) mM, followed by a decrease with Ddex concentration.
      The conjugate crystanules exhibited controlled and extended-complete release
      profile which appeared to be dictated by the concentration of the Ddex and its
      strong affinity for ibuprofen. A comparison of the real experimental with the
      predicted data using artificial neural network shows excellent correlation
      between solubility and dissolution profiles (average error=0.2348%). Heckel,
      Kawakita, Cooper-Eaton and Kuno equations were employed to determine the
      mechanism of densification during tapping process. Ddex in the crystanules
      consistently improved particle rearrangement in the order of 2.5-7 folds compared
      with pure ibuprofen and stabilized ibuprofen against fragmentation during tapping
      process. Primary and secondary particle rearrangements were the prominent
      mechanisms of densification while deformation and fragmentation did not occur.
      Lower concentrations of Ddex below its critical granular concentration (<6.25*10(
      4) mM) hindered plastic deformation and fragmentation, however, the summation of
      primary and secondary rearrangement parameters was greater than unity suggesting
      that the overall rearrangement of the conjugate crystanules cannot be explained
      exclusively by these two steps. This study has demonstrated the formulation of a
      novel ibuprofen-polymer conjugate which exhibited improved dose distribution and
      pre-compression characteristics as well as controlled and extended-complete
      release profiles - a potential drug delivery strategy for poorly soluble drugs.

PMID- 24886692
TI  - Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality
      by design approach for product construction.
AB  - An amikacin product for convenient and compliant inhalation in cystic fibrosis
      patients was constructed by spray-drying in order to produce powders of pure drug
      having high respirability and flowability. An experimental design was applied as
      a statistical tool for the characterization of amikacin spray drying process,
      through the establishment of mathematical relationships between six Critical
      Quality Attributes (CQAs) of the finished product and five Critical Process
      Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for
      particle engineering, in general did not benefit the CQAs of the spray dried
      powders for inhalation. The spray drying feed solution required the inclusion of
      10% (v/v) ethanol in order to reach the desired aerodynamic performance of
      powders. All desirable function solutions indicated that the favourable
      concentration of amikacin in the feed solution had to be kept at 1% w/v level. It
      was found that when the feed rate of the sprayed solution was raised, an increase
      in the drying temperature to the maximum value (160  degrees C) was required to
      maintain good powder respirability. Finally, the increase in drying temperature
      always led to an evident increase in emitted dose (ED) without affecting the
      desirable fine particle dose (FPD) values. The application of the experimental
      design enabled us to obtain amikacin powders with both ED and FPD, well above the
      regulatory and scientific references. The finished product contained only the
      active ingredient, which keeps low the mass to inhale for dose requirement.

PMID- 24886693
TI  - Quitters referring smokers: a quitline chain-referral pilot study.
AB  - BACKGROUND: Telephone counseling Quitlines can support smoking cessation, but are
      under-utilized. We explored the use of smoker peer-referrals to increase use of a
      Quitline in Mississippi and Alabama. FINDINGS: Collaborating with the Alabama and
      Mississippi Quitline, we piloted peer-referrals to Quitlines. Successful
      'quitters' who had used the Quitline were contacted at routine follow-up and
      recruited to participate as a peer-referrer and refer their friends and family
      who smoked to the Quitline. Peer-referrers completed a training session, received
      a manual and a set of Quitline brochures a peer-referral forms. These peer
      referral forms were then returned to the Quitline telephone counselors who
      proactively called the referred smokers. Of the initial potential pool of 96 who
      quit using the Quitline, 24 peer-referrers (75% Women, 29% African-American, and
      high school graduates/GED 67%) were recruited and initially agreed to participate
      as peer-referrers. Eleven of the 24 who initially agreed were trained, and of
      these 11, 4 (4%) actively referred 23 friends and family over 2 months. From
      these 23 new referrals, three intakes (100% Women, 66% African-American) were
      completed. Of the initial pool of 96, 4 (4%) actively participated in referring
      friends and family. Quitline staff and peer-referrers noted several barriers
      including: time-point in which potential peer-referrers were asked to
      participate, an 'overwhelming' referral form to use and limited ways to refer.
      CONCLUSIONS: Though 'quitters' were willing to agree to peer-refer, we received a
      minority of referrals. However, we identified several areas to improve this new
      method for increasing awareness and access to support systems like the Quitline
      for smokers who want to quit.

PMID- 24886694
TI  - Pulse wave velocity and neutrophil gelatinase-associated lipocalin as predictors
      of acute kidney injury following aortic valve replacement.
AB  - BACKGROUND: Accurate prediction, early detection and treatment of acute kidney
      injury (AKI) are essential for improving post-operative outcomes. This study
      aimed to examine the role of aortic stiffness and neutrophil gelatinase
      associated lipocalin (NGAL) as predictors of AKI or need for early medical renal
      intervention following aortic valve replacement (AVR). METHODS: Aortic pulse wave
      velocity and plasma NGAL were measured pre-operatively in recruited patients
      undergoing AVR for aortic stenosis (AS). Plasma NGAL was also measured at 3 and
      18-24 hours after cardiopulmonary bypass (CPB). AKI was defined using RIFLE
      criteria. Early medical renal intervention included diuretics or dopamine
      infusion exclusively for renal causes. RESULTS: Fifty-three patients aged 71 +/-
      9 years were included. Sixteen (30%) developed AKI (AKI-Yes) and 24 patients
      (45%) received early medical intervention (Intervention-Yes). There was no
      significant difference in the demographic, clinical or operative characteristics
      between the two groups for either outcome. PWV did not significantly correlate
      with AKI (r = 0.12, P = 0.13) or early intervention (r = 0.18, P = 0.18). At 3 h
      post-CPB, plasma NGAL was a much stronger predictor of both AKI and the need for
      early medical intervention than conventional markers such as creatinine (AKI: AUC
      83%, 95% CI 0.70-0.95 vs. AUC 65%, 95% CI 0.47- 0.82; Medical intervention: AUC
      84%, 95% CI 0.72-0.96 vs. AUC 56%, 95% CI 0.38-0.73). Post-CPB (3 hr) plasma NGAL
      was also significantly associated with AKI (r = 0.68, P < 0.001) at levels above
      150 ng/ml; and significantly associated with early intervention (r = 0.64, P <
      0.001) above 136 ng/ml. Simple linear regression showed no relationship between
      PWV and NGAL levels. CONCLUSION: Aortic PWV does not correlate significantly with
      post-operative AKI or plasma NGAL levels in surgical AS patients. Post-operative
      NGAL is however an early and powerful predictive biomarker of both post-operative
      AKI and the need for early medical renal intervention and should consequently be
      considered in prediction models for AKI after cardiac surgery.

PMID- 24886695
TI  - Succinate dehydrogenase deficient gastrointestinal stromal tumors (GISTs) - a
      review.
AB  - Loss of function of the succinate dehydrogenase complex characterizes a rare
      group of human tumors including some gastrointestinal stromal tumors,
      paragangliomas, renal carcinomas, and pituitary adenomas, and these can all be
      characterized as SDH-deficient tumors. Approximately 7.5% of gastric
      gastrointestinal stromal tumors are SDH-deficient and not driven by KIT/PDGFRA
      mutations, as are most other GISTs. The occurrence of SDH-deficient GISTs is
      restricted to stomach, and they typically occur in children and young adults
      representing a spectrum of clinical behavior from indolent to progressive. Slow
      progression is a common feature even after metastatic spread has taken place, and
      many patients live years with metastases. SDH-deficient GISTs have characteristic
      morphologic features including multinodular gastric wall involvement, often
      multiple separate tumors, common lymphovascular invasion, and occasional lymph
      node metastases. Diagnostic is the loss of succinate dehydrogenase subunit B
      (SDHB) from the tumor cells and this can be practically assessed by
      immunohistochemistry. SDHA is lost in cases associated with SDHA mutations.
      Approximately half of the patients have SDH subunit gene mutations, often
      germline and most commonly A (30%), and B, C or D (together 20%), with both
      alleles inactivated in the tumor cells according to the classic tumor suppressor
      gene model. Half of the cases are not associated with SDH-mutations and
      epigenetic silencing of the SDH complex is the possible pathogenesis. Extensive
      genomic methylation has been observed in these tumors, which is in contrast with
      other GISTs. SDH-loss causes succinate accumulation and activation of
      pseudohypoxia signaling via overexpression of HIF-proteins. Activation of insulin
      like growth factor 1-signaling is also typical of these tumors. SDH-deficient
      GISTs are a unique group of GISTs with an energy metabolism defect as the key
      oncogenic mechanism. This article is part of a Directed Issue entitled: Rare
      Cancers. 

PMID- 24886696
TI  - Implication of anti-inflammatory macrophages in regenerative moto-neuritogenesis:
      promotion of myoblast migration and neural chemorepellent semaphorin 3A
      expression in injured muscle.
AB  - Regenerative mechanisms that regulate intramuscular motor innervation are thought
      to reside in the spatiotemporal expression of axon-guidance molecules. Our
      previous studies proposed a heretofore unexplored role of resident myogenic stem
      cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural
      chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) triggered
      its expression exclusively at the early-differentiation phase. In order to verify
      this concept, the present study was designed to clarify a paracrine source of HGF
      release. In vitro experiments demonstrated that activated anti-inflammatory
      macrophages (CD206-positive M2) produce HGF and thereby promote myoblast
      chemoattraction and Sema3A expression. Media from pro-inflammatory macrophage
      cultures (M1) did not show any significant effect. M2 also enhanced the
      expression of myoblast-differentiation markers in culture, and infiltrated
      predominantly at the early-differentiation phase (3-5 days post-injury); M2 were
      confirmed to produce HGF as monitored by in vivo/ex vivo immunocytochemistry of
      CD11b/CD206/HGF-positive cells and by HGF in situ hybridization of cardiotoxin-
      or crush-injured tibialis anterior muscle, respectively. These studies advance
      our understanding of the stage-specific activation of Sema3A expression
      signaling. Findings, therefore, encourage the idea that M2 contribute to
      spatiotemporal up-regulation of extracellular Sema3A concentrations by producing
      HGF that, in turn, stimulates a burst of Sema3A secretion by myoblasts that are
      recruited to site of injury. This model may ensure a coordinated delay in re
      attachment of motoneuron terminals onto damaged fibers early in muscle
      regeneration, and thus synchronize the recovery of muscle-fiber integrity and the
      early resolution of inflammation after injury. 

PMID- 24886697
TI  - Discovery of single-gene inborn errors of immunity by next generation sequencing.
AB  - Many patients with clinical and laboratory evidence of primary immunodeficiency
      do not have a gene specific diagnosis. The use of next generation sequencing,
      particularly whole exome sequencing, has given us an extraordinarily powerful
      tool to identify the disease-causing genes in some of these patients. At least 34
      new gene defects have been identified in the last 4 years. These findings
      document the striking heterogeneity of the phenotype in patients with mutations
      in the same gene. In some cases this can be attributed to loss-of-function
      mutations in some patients, but gain-of-function mutations in others. In
      addition, the surprisingly high frequency of autosomal dominant
      immunodeficiencies with variable penetrance, and de novo mutations in disorders
      with a severe phenotype has been unmasked. 

PMID- 24886699
TI  - The art of war: battles between virus and host.

PMID- 24886698
TI  - Matrix assisted laser desorption ionization mass spectrometry imaging identifies
      markers of ageing and osteoarthritic cartilage.
AB  - INTRODUCTION: Cartilage protein distribution and the changes that occur in
      cartilage ageing and disease are essential in understanding the process of
      cartilage ageing and age related diseases such as osteoarthritis. The aim of this
      study was to investigate the peptide profiles in ageing and osteoarthritic (OA)
      cartilage sections using matrix assisted laser desorption ionization mass
      spectrometry imaging (MALDI-MSI). METHODS: The distribution of proteins in young,
      old and OA equine cartilage was compared following tryptic digestion of cartilage
      slices and MALDI-MSI undertaken with a MALDI SYNAPTTM HDMS system. Protein
      identification was undertaken using database searches following multivariate
      analysis. Peptide intensity differences between young, ageing and OA cartilage
      were imaged with Biomap software. Analysis of aggrecanase specific cleavage
      patterns of a crude cartilage proteoglycan extract were used to validate some of
      the differences in peptide intensity identified. Immunohistochemistry studies
      validated the differences in protein abundance. RESULTS: Young, old and OA equine
      cartilage was discriminated based on their peptide signature using discriminant
      analysis. Proteins including aggrecan core protein, fibromodulin, and cartilage
      oligomeric matrix protein were identified and localised. Fibronectin peptides
      displayed a stronger intensity in OA cartilage. Age-specific protein markers for
      collectin-43 and cartilage oligomeric matrix protein were identified. In addition
      potential fibromodulin and biglycan peptides targeted for degradation in OA were
      detected. CONCLUSIONS: MALDI-MSI provided a novel platform to study cartilage
      ageing and disease enabling age and disease specific peptides in cartilage to be
      elucidated and spatially resolved.

PMID- 24886701
TI  - Daytime and nighttime effects of brimonidine on IOP and aqueous humor dynamics in
      participants with ocular hypertension.
AB  - PURPOSE: The effects of brimonidine on daytime and nighttime intraocular pressure
      (IOP) and aqueous humor dynamics were evaluated in volunteers with ocular
      hypertension (OHT). PATIENTS AND METHODS: Thirty participants with OHT (58.6+/
      1.7 years old, mean+/-SEM) were enrolled into this randomized, double-masked,
      cross-over study. For 6 weeks, participants self-administered 0.2% brimonidine or
      placebo 3 times daily. During daytime and nighttime visits, measurements included
      aqueous flow (Fa) by fluorophotometry, outflow facility (C) by tonography,
      episcleral venous pressure (Pev) by venomanometry, and seated and supine IOP by
      pneumatonometry. Uveoscleral outflow (U) was calculated mathematically. RESULTS:
      When treated with placebo, nighttime supine Pev (11.2+/-0.25 mm Hg) was higher
      (P<0.05) compared with daytime seated Pev (10.2+/-0.25 mm Hg), and Fa and U were
      significantly reduced at night. Brimonidine significantly lowered seated IOP at
      9:00 AM and 11:00 AM, 9:00 PM and 11:00 PM and supine IOP at 9:00 AM and 11:00
      AM. Brimonidine increased U at 9 AM and 11 AM (P<0.01) and had no effect on
      daytime and nighttime Fa, C, or Pev. CONCLUSIONS: In subjects with OHT,
      brimonidine treatment for 6 weeks significantly reduces seated IOP during the day
      by increasing uveoscleral outflow. The lack of IOP effect at night can be
      explained by failure to overcome a normal nighttime reduction of uveoscleral
      outflow.

PMID- 24886702
TI  - Predictors of success in selective laser trabeculoplasty for chinese open-angle
      glaucoma.
AB  - AIM: To investigate the determinants of success of selective laser
      trabeculoplasty (SLT) in Chinese open-angle glaucoma patients. METHODS: This
      prospective cohort study sequentially recruited Chinese subjects with unilateral
      or bilateral primary open-angle glaucoma (POAG) or normal tension glaucoma (NTG).
      All subjects received a single session of 360-degree SLT treatment. Success was
      defined as IOP reduction >=20%. The following were analyzed in univariate and
      multivariate regression analyses for association with SLT success: type of
      glaucoma, age, sex, lens status, presenting IOP, pre-SLT IOP, day 1 IOP, 1-week
      IOP, number and type of anti-glaucoma medications, number of SLT shots and
      energy, retinal nerve fiber layer (RNFL) thickness, Visual Field Index,
      endothelial cell count, central corneal thickness, Snellen visual acuity, and
      spherical equivalent. RESULTS: In 111 eyes of 65 subjects, there were 51 POAG
      eyes and 60 NTG eyes. The overall success was 53.15% with a mean IOP reduction of
      19.81+/-15.93%. In univariate analysis, a thinner RNFL [coefficient=-0.027; odds
      ratio (OR)=0.95; P=0.017] was associated with success. In multivariate analysis,
      a lower day 1 IOP (coefficient=-0.29; OR=0.75; P=0.049) and using topical
      carbonic anhydrase inhibitors (CAI) (coefficient=2.92; OR=18.63; P=0.0020) were
      associated with success. In both univariate and multivariate analyses, a higher
      pre-SLT IOP significantly predicted success (coefficient=0.20/0.46; OR=1.23/1.58;
      P=0.0017/0.0011) and using 3 anti-glaucoma medications (coefficient=-1.08/-3.74;
      OR=0.3/0.024; P=0.037/P=0.0081) was associated with SLT failure. CONCLUSION: The
      positive predictors of SLT success included: higher pre-SLT IOP, use of topical
      CAI, thinner RNFL, and lower day 1 IOP. Using 3 anti-glaucoma medications was
      associated with failure.

PMID- 24886703
TI  - A prospective study of consecutive patients undergoing full-thickness
      conjunctival/scleral hypotony sutures for clinical ocular hypotony.
AB  - PURPOSE: To describe a modified suturing technique for the treatment of hypotony.
      METHODS: A prospective case series of 15 patients with hypotony from an
      overfiltering trabeculectomy underwent full-thickness hypotony sutures. The
      technique involves placing several radial interrupted 10-0 nylon sutures in the
      area of the prior trabeculectomy. The suture pass starts at the limbus, travels
      through the conjunctiva, and full-thickness sclera before exiting the
      conjunctiva. The sutures were selectively removed postoperatively to titrate the
      intraocular pressure (IOP). Hypotony resolution, IOP, visual acuity, and
      complications were assessed on postoperative visits. RESULTS: Before surgery, the
      mean IOP was 3.3 mm Hg. The mean IOP 1 day after surgery was 23.5 mm Hg, which
      settled to 12.9 mm Hg 3 months after surgery. Hypotony was reversed in 100% of
      patients and 87% achieved a goal IOP. Suture removal was performed in 73%, most
      within the first week after surgery. CONCLUSIONS: Placing full-thickness hypotony
      sutures is an effective way to treat ocular hypotony. Sutures can be removed
      postoperatively to titrate the IOP.

PMID- 24886704
TI  - Identifying aging-related genes in mouse hippocampus using gateway nodes.
AB  - BACKGROUND: High-throughput studies continue to produce volumes of metadata
      representing valuable sources of information to better guide biological research.
      With a stronger focus on data generation, analysis models that can readily
      identify actual signals have not received the same level of attention. This is
      due in part to high levels of noise and data heterogeneity, along with a lack of
      sophisticated algorithms for mining useful information. Networks have emerged as
      a powerful tool for modeling high-throughput data because they are capable of
      representing not only individual biological elements but also different types of
      relationships en masse. Moreover, well-established graph theoretic methodology
      can be applied to network models to increase efficiency and speed of analysis. In
      this project, we propose a network model that examines temporal data from mouse
      hippocampus at the transcriptional level via correlation of gene expression.
      Using this model, we formally define the concept of "gateway" nodes, loosely
      defined as nodes representing genes co-expressed in multiple states. We show that
      the proposed network model allows us to identify target genes implicated in
      hippocampal aging-related processes. RESULTS: By mining gateway genes related to
      hippocampal aging from networks made from gene expression in young and middle
      aged mice, we provide a proof-of-concept of existence and importance of gateway
      nodes. Additionally, these results highlight how network analysis can act as a
      supplement to traditional statistical analysis of differentially expressed genes.
      Finally, we use the gateway nodes identified by our method as well as functional
      databases and literature to propose new targets for study of aging in the mouse
      hippocampus. CONCLUSIONS: This research highlights the need for methods of
      temporal comparison using network models and provides a systems biology approach
      to extract information from correlation networks of gene expression. Our results
      identify a number of genes previously implicated in the aging mouse hippocampus
      related to synaptic plasticity and apoptosis. Additionally, this model identifies
      a novel set of aging genes previously uncharacterized in the hippocampus. This
      research can be viewed as a first-step for identifying the processes behind
      comparative experiments in aging that is applicable to any type of temporal multi
      state network.

PMID- 24886705
TI  - CaMKII and MEK1/2 inhibition time-dependently modify inflammatory signaling in
      rat cerebral arteries during organ culture.
AB  - BACKGROUND: Cerebral ischemia induces transcriptional upregulation of
      inflammatory genes in the brain parenchyma and in cerebral arteries, thereby
      contributing to the infarct development. The present study was designed to
      evaluate the involvement of calcium-calmodulin-dependent protein kinase (CaMKII)
      II and extracellular signal-regulated kinase1/2 (ERK1/2) on inflammatory
      mediators in rat cerebral arteries using organ culture as a method for inducing
      ischemic-like vascular wall changes. METHODS: Rat basilar arteries were cultured
      in serum-free medium for 0, 3, 6 or 24 hours in the presence or absence of the
      CaMKII inhibitor KN93 or the MEK1/2 inhibitor U0126. Protein expression of
      activated CaMKII, ERK1/2, and inflammatory-associated protein kinases and
      mediators were examined with western blot and immunohistochemistry. Caspase-3
      mRNA levels in basilar arteries were studied with real-time PCR. RESULTS: Western
      blot evaluation showed that organ culture induced a significant increase in
      phosphorylated ERK1/2 at 3, 6 and 24 hours, while CaMKII was found to be already
      activated in fresh non-incubated arteries and to decrease with incubation time.
      The addition of U0126 or KN93 decreased levels of phosphorylated c-Jun N-terminal
      kinase and p-p38, as evaluated by immunohistochemistry. KN93 affected the
      increase in caspase-3 mRNA expression only when given at the start of incubation,
      while U0126 had an inhibitory effect when given up to six hours later. Tumor
      necrosis factor receptor 1 was elevated after organ culture. This inflammatory
      marker was reduced by both of the two different protein kinase inhibitors.
      CONCLUSIONS: The novel findings of the present study are that the cross-talk
      between the two protein kinases and the inhibition of CaMKII or MEK1/2 in a time
      dependent manner attenuates inflammatory-associated protein kinases and
      mediators, suggesting that they play a role in cerebrovascular inflammation.

PMID- 24886706
TI  - Role of Ubiquitylation in Controlling Suppressor of Cytokine Signalling 3 (SOCS3)
      Function and Expression.
AB  - The realisation that unregulated activation of the Janus kinase-signal transducer
      and activator of transcription (JAK-STAT) pathway is a key driver of a wide range
      of diseases has identified its components as targets for therapeutic intervention
      by small molecule inhibitors and biologicals. In this review, we discuss JAK-STAT
      signalling pathway inhibition by the inducible inhibitor "suppressor of cytokine
      signaling 3 (SOCS3), its role in diseases such as myeloproliferative disorders,
      and its function as part of a multi-subunit E3 ubiquitin ligase complex. In
      addition, we highlight potential applications of these insights into SOCS3-based
      therapeutic strategies for management of conditions such as vascular re-stenosis
      associated with acute vascular injury, where there is strong evidence that
      multiple processes involved in disease progression could be attenuated by
      localized potentiation of SOCS3 expression levels. 

PMID- 24886707
TI  - Separated right and left ventricular excitation during right ventricular septal
      pacing in a patient with narrow QRS wave: a case report.
AB  - INTRODUCTION: Right ventricular septal pacing is thought to be better than right
      ventricular apical pacing for shortening the QRS duration and for preserving left
      ventricular function. However, right ventricular septal pacing may not be
      effective in all cases. In this case report, we present a rare case in which
      right ventricular septal pacing induced thoroughly separated right and left
      ventricular excitation despite the presence of a relatively narrow QRS wave
      during atrium-only pacing. CASE PRESENTATION: We report a case of 63-year-old
      Japanese man with cardiomyopathy with an implantable cardioverter defibrillator
      placement for ventricular tachycardia. Three years after implantation, he
      developed second-degree atrio-ventricular block. Therefore, atrio-ventricular
      sequential pacing was started; then his heart failure was much worsened. His
      electrocardiogram showed a dissociated biphasic QRS wave during right ventricular
      high-septal pacing, despite the presence of a non-fragmented QRS morphology
      during atrium-only pacing. An activation map during right ventricular high-septal
      pacing showed that right ventricular conduction started at the pacing site and
      ended at the right ventricular basal inferior site. Subsequently after a 10 ms
      interval, left ventricular conduction started at the left ventricular
      posteroseptum and ended at the left ventricular lateral wall. These data indicate
      that during right ventricular high-septal pacing, the first component of the QRS
      wave supposedly reflects only right ventricular excitation and the second
      component only left ventricular excitation. Also due to the intracardiac
      electrograms, it was assumed that this phenomenon was caused by transversely
      limited severe transseptal conduction disturbance. CONCLUSION: It should be noted
      that even ventricular septal pacing could evoke harmful interventricular
      dyssynchrony due to transversely limited severe septal conduction disturbance,
      despite the presence of a relatively narrow QRS wave.

PMID- 24886708
TI  - Native T1-mapping detects the location, extent and patterns of acute myocarditis
      without the need for gadolinium contrast agents.
AB  - BACKGROUND: Acute myocarditis can be diagnosed on cardiovascular magnetic
      resonance (CMR) using multiple techniques, including late gadolinium enhancement
      (LGE) imaging, which requires contrast administration. Native T1-mapping is
      significantly more sensitive than LGE and conventional T2-weighted (T2W) imaging
      in detecting myocarditis. The aims of this study were to demonstrate how to
      display the non-ischemic patterns of injury and to quantify myocardial
      involvement in acute myocarditis without the need for contrast agents, using
      topographic T1-maps and incremental T1 thresholds. METHODS: We studied 60
      patients with suspected acute myocarditis (median 3 days from presentation) and
      50 controls using CMR (1.5 T), including: (1) dark-blood T2W imaging; >(2) native
      T1-mapping (ShMOLLI); (3) LGE. Analysis included: (1) global myocardial T2 signal
      intensity (SI) ratio compared to skeletal muscle; (2) myocardial T1 times; (3)
      areas of injury by T2W, T1-mapping and LGE. RESULTS: Compared to controls,
      patients had more edema (global myocardial T2 SI ratio 1.71 +/- 0.27 vs.1.56 +/-
      0.15), higher mean myocardial T1 (1011 +/- 64 ms vs. 946 +/- 23 ms) and more
      areas of injury as detected by T2W (median 5% vs. 0%), T1 (median 32% vs. 0.7%)
      and LGE (median 11% vs. 0%); all p < 0.001. A threshold of T1 > 990 ms
      (sensitivity 90%, specificity 88%) detected significantly larger areas of
      involvement than T2W and LGE imaging in patients, and additional areas of injury
      when T2W and LGE were negative. T1-mapping significantly improved the diagnostic
      confidence in an additional 30% of cases when at least one of the conventional
      methods (T2W, LGE) failed to identify any areas of abnormality. Using incremental
      thresholds, T1-mapping can display the non-ischemic patterns of injury typical of
      myocarditis. CONCLUSION: Native T1-mapping can display the typical non-ischemic
      patterns in acute myocarditis, similar to LGE imaging but without the need for
      contrast agents. In addition, T1-mapping offers significant incremental
      diagnostic value, detecting additional areas of myocardial involvement beyond T2W
      and LGE imaging and identified extra cases when these conventional methods failed
      to identify abnormalities. In the future, it may be possible to perform
      gadolinium-free CMR using cine and T1-mapping for tissue characterization and may
      be particularly useful for patients in whom gadolinium contrast is
      contraindicated.

PMID- 24886710
TI  - JMJD2A contributes to breast cancer progression through transcriptional
      repression of the tumor suppressor ARHI.
AB  - INTRODUCTION: Breast cancer is a worldwide health problem and the leading cause
      of cancer death among females. We previously identified Jumonji domain containing
      2A (JMJD2A) as a critical mediator of breast cancer proliferation, migration and
      invasion. We now report that JMJD2A could promote breast cancer progression
      through transcriptional repression of the tumor suppressor aplasia Ras homolog
      member I (ARHI). METHODS: Immunohistochemistry was performed to examine protein
      expressions in 155 cases of breast cancer and 30 non-neoplastic tissues. Spearman
      correlation analysis was used to analyze the correlation between JMJD2A
      expression and clinical parameters as well as several tumor regulators in 155
      cases of breast cancer. Gene and protein expressions were monitored by
      quantitative polymerase chain reaction (qPCR) and Western blot. Results from
      knockdown of JMJD2A, overexpression of JMJD2A, Co-immunoprecipitation (Co-IP)
      assay, dual luciferase reporter gene assay and chromatin immunoprecipitation
      (ChIP) elucidated molecular mechanisms of JMJD2A action in breast cancer
      progression. Furthermore, the effects of ARHI overexpression on JMJD2A-mediated
      tumor progression were investigated in vitro and in vivo. For in vitro
      experiments, cell proliferation, wound-healing, migration and invasion were
      monitored by cell counting, scratch and Boyden Chamber assays. For in vivo
      experiments, control cells and cells stably expressing JMJD2A alone or together
      with ARHI were inoculated into mammary fat pads of mice. Tumor volume, tumor
      weight and metastatic nodules were measured by caliper, electronic balance and
      nodule counting, respectively. RESULTS: JMJD2A was highly expressed in human
      breast cancers and positively correlated with tumor progression. Knockdown of
      JMJD2A increased ARHI expression whereas overexpression of JMJD2A decreased ARHI
      expression at both protein and mRNA levels. Furthermore, E2Fs and histone
      deacetylases were involved in the transcriptional repression of ARHI expression
      by JMJD2A. And the aggressive behavior of JMJD2A in breast cancers could be
      reversed by re-expression of ARHI in vitro and in vivo. CONCLUSION: We
      demonstrated a cancer-promoting effect of JMJD2A and defined a novel molecular
      pathway contributing to JMJD2A-mediated breast cancer progression.

PMID- 24886711
TI  - Hyaluronidase injection for the treatment of eyelid edema: a retrospective
      analysis of 20 patients.
AB  - BACKGROUND: Hyaluronidase (Hylase Dessau((r))) is a hyaluronic acid-metabolizing
      enzyme, which has been shown to loosen the extracellular matrix, thereby
      improving the diffusion of local anesthetics. Lower eyelid edema is a common post
      interventional complication of cosmetic procedures performed in the lid region,
      such as the injection of hyaluronic acid fillers for tear-trough augmentation.
      The purpose of this study was to validate the efficacy of hyaluronidase in the
      management of lower eyelid edema. METHODS: We performed a retrospective analysis
      with 20 patients with lower eyelid edema. Most patients (n = 14) presented with
      edema following hyaluronic acid injection (tear-trough augmentation), whereas the
      minority (n = 6) were treated due to idiopathic edema (malar edema or malar
      mounds). Patients were treated by local infiltration of approximately 0.2 ml to
      0.5 ml of hyaluronidase (Hylase Dessau((r)) 20 IU to 75 IU) per eyelid.
      Photographs were taken prior to and seven days after infiltration. RESULTS:
      Hyaluronidase was found to reduce effectively and rapidly or resolve eyelid edema
      after a single injection. No relevant adverse effects were observed. However, it
      must be noted that a hyaluronidase injection may also dissolve injected
      hyaluronic acid fillers and may therefore negatively affect tear-trough
      augmentations. While the effects of a treatment for edema due to tear-trough
      augmentation were permanent, malar edema and malar mounds reoccurred within two
      to three weeks. CONCLUSION: The infiltration of hyaluronidase is rapid, safe and
      currently the only effective option for the management of eyelid edema. No
      relevant adverse effects were observed.

PMID- 24886712
TI  - Is pentobarbital safe and efficacious in the treatment of super-refractory status
      epilepticus: a cohort study.
AB  - INTRODUCTION: Seizures refractory to third-line therapy are also labeled super
      refractory status epilepticus (SRSE). These seizures are extremely difficult to
      control and associated with poor outcome. We aimed to characterize efficacy and
      side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE.
      METHODS: We retrospectively reviewed continuous electroencephalography (cEEG)
      reports for all adults with RSE treated with cIV-PTB between May 1997 and April
      2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB
      for reasons other than RSE were excluded. We collected baseline information, cEEG
      findings, side-effects and functional outcome at discharge and one year. RESULTS:
      Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age
      was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of
      epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV
      PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying
      etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis),
      remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90%
      (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB,
      despite the fact that suppression-burst was attained in 90% (N = 28) of patients
      and persisted >72 hours in 56% (N = 17). Weaning was successful after adding
      phenobarbital in 80% (12/15 of the patients with withdrawal seizures).
      Complications during or after cIV-PTB included pneumonia (32%, N = 10),
      hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N =
      4), and one patient each with propylene glycol toxicity and cardiac arrest. One
      third (35%, N = 11) had no identified new complication after starting cIV-PTB. At
      one year after discharge, 74% (N = 23) were dead or in a state of unresponsive
      wakefulness, 16% (N = 5) severely disabled, and 10% (N = 3) had no or minimal
      disability. Death or unresponsive wakefulness was associated with catastrophic
      etiology (p = 0.03), but none of the other collected variables. CONCLUSIONS: cIV
      PTB effectively aborts SRSE and complications are infrequent; outcome in this
      highly refractory cohort of patients with devastating underlying etiologies
      remains poor. Phenobarbital may be particularly helpful when weaning cIV-PTB.

PMID- 24886713
TI  - Mechanic's hands revisited: is this sign still useful for diagnosis in patients
      with lung involvement of collagen vascular diseases?
AB  - BACKGROUND: The presence of "mechanic's hands" is one of the clinical clues for
      collagen vascular diseases. However, the exact relevance of "mechanic's hands" in
      collagen vascular diseases has not been well documented. The aim of this study
      was to clarify the relevance of "mechanic's hands" to collagen vascular diseases
      including various skin lesions and interstitial pneumonia. METHODS: A
      retrospective review of the medical records of patients with "mechanic's hands"
      at our hospital between April 2011 and December 2012 was conducted. A PubMed
      search was also conducted using the term "mechanic's hands". RESULTS: Four
      patients in our institution and 40 patients obtained from PubMed who had
      "mechanic's hands" were identified. The most frequent diseases were DM/amyopathic
      DM (n = 24, 54.5%) and anti-ARS syndrome (n = 17, 38.6%). In these patients, the
      major skin lesions associated with "mechanic's hands" were periungual erythema (n
      = 23, 52.3%), Gottron's sign (n = 17, 38.6%), heliotrope rash (n = 10, 22.7%),
      Raynaud's phenomenon (n = 9, 20.5%), and anti-ARS syndrome (n = 17, 38.6%). Six
      cases (2 DM, 4 anti-ARS syndrome) had only "mechanic's hands". Antibodies to anti
      ARS (n = 24) were Jo-1 (n = 19), PL-7 (n = 3), OJ (n = 1), and PL-12 (n = 1).
      CONCLUSION: The presence of "mechanic's hands" together with diverse skin lesions
      could be a clinical clue to the diagnosis of lung involvement associated with
      collagen vascular diseases, especially in anti-ARS syndrome or DM/amyopathic DM.

PMID- 24886709
TI  - Amerindian-specific regions under positive selection harbour new lipid variants
      in Latinos.
AB  - Dyslipidemia and obesity are especially prevalent in populations with Amerindian
      backgrounds, such as Mexican-Americans, which predispose these populations to
      cardiovascular disease. Here we design an approach, known as the cross-population
      allele screen (CPAS), which we conduct prior to a genome-wide association study
      (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk
      genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only
      those differing in frequency between the two populations, we identify novel
      Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt
      inducible kinase 3 (SIK3), and three loci previously unassociated with
      dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and
      apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk
      variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus
      underwent positive selection in Mexicans. Furthermore, after a high-fat meal, the
      SIK3 risk variant carriers display high triglyceride levels. These findings
      suggest that Amerindian-specific genetic architecture leads to a higher incidence
      of dyslipidemia and obesity in modern Mexicans. 

PMID- 24886714
TI  - Ngram-derived pattern recognition for the detection and prediction of epileptic
      seizures.
AB  - This work presents a new method that combines symbol dynamics methodologies with
      an Ngram algorithm for the detection and prediction of epileptic seizures. The
      presented approach specifically applies Ngram-based pattern recognition, after
      data pre-processing, with similarity metrics, including the Hamming distance and
      Needlman-Wunsch algorithm, for identifying unique patterns within epochs of time.
      Pattern counts within each epoch are used as measures to determine seizure
      detection and prediction markers. Using 623 hours of intracranial
      electrocorticogram recordings from 21 patients containing a total of 87 seizures,
      the sensitivity and false prediction/detection rates of this method are
      quantified. Results are quantified using individual seizures within each case for
      training of thresholds and prediction time windows. The statistical significance
      of the predictive power is further investigated. We show that the method
      presented herein, has significant predictive power in up to 100% of temporal lobe
      cases, with sensitivities of up to 70-100% and low false predictions (dependant
      on training procedure). The cases of highest false predictions are found in the
      frontal origin with 0.31-0.61 false predictions per hour and with significance in
      18 out of 21 cases. On average, a prediction sensitivity of 93.81% and false
      prediction rate of approximately 0.06 false predictions per hour are achieved in
      the best case scenario. This compares to previous work utilising the same data
      set that has shown sensitivities of up to 40-50% for a false prediction rate of
      less than 0.15/hour. 

PMID- 24886715
TI  - Reproducibility of Fatmax and fat oxidation rates during exercise in
      recreationally trained males.
AB  - Aerobic exercise training performed at the intensity eliciting maximal fat
      oxidation (Fat(max)) has been shown to improve the metabolic profile of obese
      patients. However, limited information is available on the reproducibility of
      Fat(max) and related physiological measures. The aim of this study was to assess
      the intra-individual variability of: a) Fat(max) measurements determined using
      three different data analysis approaches and b) fat and carbohydrate oxidation
      rates at rest and at each stage of an individualized graded test. Fifteen healthy
      males [body mass index 23.1 +/- 0.6 kg/m(2), maximal oxygen consumption (VO2max)
      52.0 +/- 2.0 ml/kg/min] completed a maximal test and two identical submaximal
      incremental tests on ergocycle (30-min rest followed by 5-min stages with
      increments of 7.5% of the maximal power output). Fat and carbohydrate oxidation
      rates were determined using indirect calorimetry. Fat(max) was determined with
      three approaches: the sine model (SIN), measured values (MV) and 3rd polynomial
      curve (P3). Intra-individual coefficients of variation (CVs) and limits of
      agreement were calculated. CV for Fat(max) determined with SIN was 16.4% and
      tended to be lower than with P3 and MV (18.6% and 20.8%, respectively). Limits of
      agreement for Fat(max) were -2 +/- 27% of VO2max with SIN, -4 +/- 32 with P3 and 
      4 +/- 28 with MV. CVs of oxygen uptake, carbon dioxide production and respiratory
      exchange rate were <10% at rest and <5% during exercise. Conversely, CVs of fat
      oxidation rates (20% at rest and 24-49% during exercise) and carbohydrate
      oxidation rates (33.5% at rest, 8.5-12.9% during exercise) were higher. The intra
      individual variability of Fat(max) and fat oxidation rates was high (CV>15%),
      regardless of the data analysis approach employed. Further research on the
      determinants of the variability of Fat(max) and fat oxidation rates is required.

PMID- 24886717
TI  - Ecological aspects of the Phlebotominae fauna (Diptera: Psychodidae) in the
      Xakriaba Indigenous Reserve, Brazil.
AB  - BACKGROUND: Sand fly collections were performed to study ecological aspects of
      the Phlebotominae fauna of the Xakriaba Indigenous Reserve, an area with endemic
      cutaneous leishmaniasis, located in the state of Minas Gerais, Brazil. METHODS:
      The collections were performed in peridomicile areas and along trails previously
      selected for the study of wild and synanthropic Leishmania hosts. Differences in
      the distribution patterns of the sand fly species as well as in species richness
      and abundance between the different ecotopes were investigated during both rainy
      and dry seasons over the course of the study period. RESULTS: A total of 8,046
      sand flies belonging to 11 genera and 28 species were collected. Lutzomyia
      longipalpis and Nyssomyia intermedia were the most abundant species in
      peridomicile areas, whereas Martinsmyia minasensis and Lutzomyia cavernicola were
      the most abundant species among the different trail ecotopes. CONCLUSION: The
      different composition of the sand fly fauna observed in the peridomicile areas
      and in the trails during the study, reinforces the importance of sampled
      different areas in a phlebotomine fauna survey. The presence of Lutzomyia
      longipalpis and Ny. Intermedia most abundant in peridomicile can be important to
      Leishmania infantum and Leishmania braziliensis transmission in the Imbaubas
      native village.

PMID- 24886716
TI  - A treatment with a protease inhibitor recombinant from the cattle tick
      (Rhipicephalus Boophilus microplus) ameliorates emphysema in mice.
AB  - AIMS: To determine whether a serine protease inhibitor treatment can prevent or
      minimize emphysema in mice. METHODS: C57BL/6 mice were subjected to porcine
      pancreatic elastase (PPE) nasal instillation to induce emphysema and were treated
      with a serine protease inhibitor (rBmTI-A) before (Protocol 1) and after
      (Protocol 2) emphysema development. In both protocols, we evaluated lung function
      to evaluate the airway resistance (Raw), tissue damping (Gtis) and tissue
      elastance (Htis). The inflammatory profile was analyzed in the bronchoalveolar
      lavage (BALF) and through the use of morphometry; we measured the mean linear
      intercept (Lm) (to verify alveolar enlargement), the volume proportion of
      collagen and elastic fibers, and the numbers of macrophages and metalloprotease
      12 (MMP-12) positive cells in the parenchyma. We showed that at both time points,
      even after the emphysema was established, the rBmTI-A treatment was sufficient to
      reverse the loss of elastic recoil measured by Htis, the alveolar enlargement and
      the increase in the total number of cells in the BALF, with a primary decrease in
      the number of macrophages. Although, the treatment did not control the increase
      in macrophages in the lung parenchyma, it was sufficient to decrease the number
      of positive cells for MMP-12 and reduce the volume of collagen fibers, which was
      increased in PPE groups. These findings attest to the importance of MMP-12 in PPE
      induced emphysema and suggest that this metalloprotease could be an effective
      therapeutic target.

PMID- 24886718
TI  - Protective epitopes of the Plasmodium falciparum SERA5 malaria vaccine reside in
      intrinsically unstructured N-terminal repetitive sequences.
AB  - The malaria vaccine candidate antigen, SE36, is based on the N-terminal 47 kDa
      domain of Plasmodium falciparum serine repeat antigen 5 (SERA5). In
      epidemiological studies, we have previously shown the inhibitory effects of SE36
      specific antibodies on in vitro parasite growth and the negative correlation
      between antibody level and malaria symptoms. A phase 1 b trial of the BK-SE36
      vaccine in Uganda elicited 72% protective efficacy against symptomatic malaria in
      children aged 6-20 years during the follow-up period 130-365 days post-second
      vaccination. Here, we performed epitope mapping with synthetic peptides covering
      the whole sequence of SE36 to identify and map dominant epitopes in Ugandan adult
      serum presumed to have clinical immunity to P. falciparum malaria. High titer
      sera from the Ugandan adults predominantly reacted with peptides corresponding to
      two successive N-terminal regions of SERA5 containing octamer repeats and serine
      rich sequences, regions of SERA5 that were previously reported to have limited
      polymorphism. Affinity purified antibodies specifically recognizing the octamer
      repeats and serine rich sequences exhibited a high antibody-dependent cellular
      inhibition (ADCI) activity that inhibited parasite growth. Furthermore, protein
      structure predictions and structural analysis of SE36 using spectroscopic methods
      indicated that N-terminal regions possessing inhibitory epitopes are
      intrinsically unstructured. Collectively, these results suggest that strict
      tertiary structure of SE36 epitopes is not required to elicit protective
      antibodies in naturally immune Ugandan adults. 

PMID- 24886719
TI  - Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation.
AB  - BACKGROUND: Dysregulated microRNA (miRNA) expression contributes to cancer cell
      proliferation, apoptosis and angiogenesis. Angiogenesis is a hallmark of multiple
      myeloma (MM) development and progression. Argonaute 2 (AGO2) protein, a core
      component of the RNA-induced silencing complex (RISC), can directly bind to
      miRNAs and mediate target messenger RNA (mRNA) degradation. A previous study
      showed that AGO2 knockdown suppressed human umbilical vein endothelial cell
      (HUVEC) growth and tube formation. However, the roles and molecular mechanisms of
      AGO2-induced myeloma angiogenesis are not yet fully understood. The aim of this
      study was to characterize these roles and effects and their associated
      mechanisms. RESULTS: Supernatants from AGO2-overexpressing MM lines induced HUVEC
      migration and accelerated tube formation. Conversely, supernatants from AGO2
      knockdown MM lines suppressed HUVEC cell migration and tube formation. Moreover,
      a chick chorioallantoic membrane (CAM) assay was used to demonstrate that AGO2
      could drive neovessel formation in MM lines in vivo. Using an miRNA microarray,
      we observed that 25 miRNAs were upregulated and 7 were downregulated in response
      to AGO2. Most let-7 family members and 2 miR-17/92 cluster members (miR-17a and
      miR-92-1), all known pro-angiogenic miRNAs, were positively regulated by AGO2
      whereas anti-angiogenic miRNAs such as miR-145 and miR-361 were negatively
      regulated by AGO2. CONCLUSIONS: We conclude that AGO2 can drive neovessel
      formation in vitro and in vivo by dysregulating the expression of some angiogenic
      miRNAs. The pro-angiogenic miRNAs of the let-7 family and the miR-17/92 cluster,
      along with the anti-angiogenic miRNA miR-145, play crucial roles in AGO2-mediated
      angiogenesis by targeting angiogenesis-related genes.

PMID- 24886721
TI  - Multifaceted defense against antagonistic microbes in developing offspring of the
      parasitoid wasp Ampulex compressa (Hymenoptera, Ampulicidae).
AB  - Effective antimicrobial strategies are essential adaptations of insects to
      protect themselves, their offspring, and their foods from microbial pathogens and
      decomposers. Larvae of the emerald cockroach wasp, Ampulex compressa, sanitize
      their cockroach hosts, Periplaneta americana, with a cocktail of nine
      antimicrobials comprising mainly (R)-(-)-mellein and micromolide. The blend of
      these antimicrobials has broad-spectrum antimicrobial activity. Here we explore
      the spatio-temporal pattern of deployment of antimicrobials during the
      development from egg to adult as well as their physico-chemical properties to
      assess how these aspects may contribute to the success of the antimicrobial
      strategy. Using gas chromatography/mass spectrometry (GC/MS) we show that larvae
      start sanitizing their food as soon as they have entered their host to feed on
      its tissue. Subsequently, they impregnate the cockroach carcass with
      antimicrobials to create a hygienic substrate for cocoon spinning inside the
      host. Finally, the antimicrobials are incorporated into the cocoon. The
      antimicrobial profiles on cockroach and wasp cocoon differed markedly. While
      micromolide persisted on the cockroaches until emergence of the wasps, solid
      phase microextraction sampling and GC/MS analysis revealed that (R)-(-)-mellein
      vaporized from the cockroaches and accumulated in the enclosed nest. In microbial
      challenge assays (R)-(-)-mellein in the headspace of parasitized cockroaches
      inhibited growth of entomopathogenic and opportunistic microbes (Serratia
      marcescens, Aspergillus sydowii, Metarhizium brunneum). We conclude that, in
      addition to food sanitation, A. compressa larvae enclose themselves in two
      defensive walls by impregnating the cocoon and the cockroach cuticle with
      antimicrobials. On top of that, they use vaporous (R)-(-)-mellein to sanitize the
      nest by fumigation. This multifaceted antimicrobial defense strategy involving
      the spatially and temporally coordinated deployment of several antimicrobials in
      solution and vapor form has apparently evolved to reliably protect the larvae
      themselves and their food against a broad range of antagonistic microbes. 

PMID- 24886720
TI  - Large-scale patterns of genetic variation in a female-biased dispersing
      passerine: the importance of sex-based analyses.
AB  - Dispersal affects the distribution, dynamics and genetic structure of natural
      populations, and can be significantly different between sexes. However,
      literature records dealing with the dispersal of migratory birds are scarce, as
      migratory behaviour can notably complicate the study of dispersal. We used the
      barn swallow Hirundo rustica as model taxon to investigate patterns of genetic
      variability in males and in females of a migratory species showing sex-biased
      dispersal. We collected blood samples (n = 186) over the period 2006 to 2011 from
      adults (H. r. rustica subspecies) nesting in the same breeding site at either
      high (Ireland, Germany and Russia) or low (Spain, Italy and Cyprus) latitude
      across Europe. We amplified the Chromo Helicase DNA gene in all birds in order to
      warrant a sex-balanced sample size (92 males, 94 females). We investigated both
      uniparental (mitochondrial ND2 gene) and biparental (microsatellite DNA: 10 loci)
      genetic systems. The mtDNA provided evidence for demographic expansion yet no
      significant partition of the genetic variability was disclosed. Nevertheless, a
      comparatively distant Russian population investigated in another study, whose
      sequences were included in the present dataset, significantly diverged from all
      other ones. Different to previous studies, microsatellites highlighted remarkable
      genetic structure among the studied populations, and pointed to the occurrence of
      differences between male and female barn swallows. We produced evidence for non
      random patterns of gene flow among barn swallow populations probably mediated by
      female natal dispersal, and we found significant variability in the philopatry of
      males of different populations. Our data emphasize the importance of taking into
      account the sex of sampled individuals in order to obtain reliable inferences on
      species characterized by different patterns of dispersal between males and
      females. 

PMID- 24886723
TI  - Defect-induced semiconductor to metal transition in graphene monoxide.
AB  - This study investigates the influence of point defects on the geometric and
      electronic structure of graphene monoxide (GMO) via density functional theory
      calculations. In aspects of defect formation energy, GMOs with oxygen vacancies
      and bridge interstitial defects are more likely to form when compared to GMOs
      with defects such as carbon vacancies and hollow interstitial defects. It was
      also found that the oxygen vacancy or the hollow interstitial defect induces
      local tensile strain around the defective site and this strain increases the band
      gap energy of the defective GMO. In addition, the band gaps of GMO with carbon
      vacancies or bridge interstitial defects decreased mainly due to the dangling
      bonds, not due to the strain effect. It is noted that the dangling bond derived
      from the defects forms the defect-level in the band gap of GMO. The semiconductor
      to metal transition by the band gap change (0-0.7 eV) implies the possibility for
      band gap engineering of GMO by vacancies and interstitial defects. 

PMID- 24886722
TI  - Untying a nanoscale knotted polymer structure to linear chains for efficient gene
      delivery in vitro and to the brain.
AB  - The purpose of this study was to develop a platform transfection technology, for
      applications in the brain, which could transfect astrocytes without requiring
      cell specific functionalization and without the common cause of toxicity through
      high charge density. Here we show that a simple and scalable preparation
      technique can be used to produce a "knot" structured cationic polymer, where
      single growing chains can crosslink together via disulphide intramolecular
      crosslinks (internal cyclizations). This well-defined knot structure can thus
      "untie" under reducing conditions, showing a more favorable transfection profile
      for astrocytes compared to 25 kDa-PEI (48-fold), SuperFect(r) (39-fold) and
      Lipofectamine(r)2000 (18-fold) whilst maintaining neural cell viability at over
      80% after four days of culture. The high transfection/lack of toxicity of this
      knot structured polymer in vitro, combined with its ability to mediate luciferase
      transgene expression in the adult rat brain, demonstrates its use as a platform
      transfection technology which should be investigated further for
      neurodegenerative disease therapies. 

PMID- 24886724
TI  - Low-dose insulin-like growth factor binding proteins 1 and 2 and angiopoietin
      like protein 3 coordinately stimulate ex vivo expansion of human umbilical cord
      blood hematopoietic stem cells as assayed in NOD/SCID gamma null mice.
AB  - INTRODUCTION: Insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs)
      and angiopoietin-like proteins (ANGPTLs) can enhance the ex vivo expansion of
      hematopoietic stem cells (HSCs) when used with a standard cytokine cocktail of
      stem cell factor (SCF), thrombopoietin (TPO) and FLT3 ligand (FL). In order to
      determine the optimal dose and combination of IGFs, IGFBPs and ANGPTLs, serial
      dilution and full permutation of IGFBP1, IGFBP2, IGF2 and ANGPTL3 were applied on
      a cryopreserved umbilical cord blood mononuclear cell (UCB-MNC) ex vivo expansion
      system. METHODS: In this system, 4 * 105 cells/ml of UCB-MNCs were inoculated in
      serum-free Stemspan(r) medium (Stemcell technologies, vancouver, BC, Canada)
      supplied with standard basal cytokine combination of 100 ng/ml SCF, 50 ng/ml FL
      and 100 ng/ml TPO and supported by a bone marrow mesenchymal stromal cell layer.
      RESULTS: Paradoxically, experiment results showed that the highest expansion of
      CD34+CD38-CD90+ primitive progenitor was stimulated by cytokine combination of
      SCF + TPO + FL + IGFBP1 + IGFBP2 + ANGPTL3 at a low dose of 15 ng/ml IGFBP1 and
      20 ng/ml IGFBP2 and ANGPTL3. This ex vivo expansion was further validated in 8
      week-old to 10-week-old nonobese diabetic/severe combined immunodeficiency
      interleukin 2 gamma chain null (NOD/SCID-IL2Rgamma-/-) mice. Limiting dilution
      assay showed excellent correlation between the HSC ex vivo surface marker of
      CD34+CD38-CD90+ and the in vivo competitive repopulating unit (CRU) functional
      assay. CONCLUSION: IGFBP1, IGFBP2, IGF2 and ANGPTL3 can stimulate the expansion
      of CD34+CD38-CD90+ primitive progenitor at low dose. The optimal combination
      comprises IGFBP1, IGFBP2 and ANGPTL3 together with the standard cytokine cocktail
      of SCF, FL and TPO. The CD34+CD38-CD90+ phenotype can serve as a surrogate ex
      vivo surface marker for HSCs due to consistency with the in vivo CRU functional
      assay.

PMID- 24886726
TI  - Frailty screening comes of age.

PMID- 24886727
TI  - Improving care for community dwelling frail elders through patient and provider
      engagement.

PMID- 24886729
TI  - A step forward in the right direction.

PMID- 24886728
TI  - Description of 1,108 older patients referred by their physician to the "Geriatric
      Frailty Clinic (G.F.C) for Assessment of Frailty and Prevention of Disability" at
      the gerontopole.
AB  - INTRODUCTION: Frailty is considered as an early stage of disability which,
      differently from disability, is still amenable for preventive interventions and
      is reversible. In 2011, the "Geriatric Frailty Clinic (G.F.C) for Assessment of
      Frailty and Prevention of Disability" was created in Toulouse, France, in
      association with the University Department of General Medicine and the Midi
      Pyrenees Regional Health Authority. This structure aims to support the
      comprehensive and multidisciplinary assessment of frail older persons, to
      identify the specific causes of frailty and to design a personalized preventive
      plan of intervention against disability. In the present paper, we describe the
      G.F.C structure, organization, details of the global evaluation and preventive
      interventions against disability, and provide the main characteristics of the
      first 1,108 patients evaluated during the first two years of operation. METHODS:
      Persons aged 65 years and older, considered as frail by their physician (general
      practitioner, geriatrician or specialist) in the Toulouse area, are invited to
      undergo a multidisciplinary evaluation at the G.F.C. Here, the individual is
      assessed in order to detect the potential causes for frailty and/or disability.
      At the end of the comprehensive evaluation, the team members propose to the
      patient (in agreement with the general practitioner) a Personalized Prevention
      Plan (PPP) specifically tailored to his/her needs and resources. The G.F.C also
      provides the patient's follow-up in close connection with family physicians.
      RESULTS: Mean age of our population was 82.9 +/- 6.1 years. Most patients were
      women (n=686, 61.9%). According to the Fried criteria, 423 patients (39.1%) were
      pre-frail, and 590 (54.5%) frail. Mean ADL (Activities of Daily Living) score was
      5.5 +/- 1.0. Consistently, IADL (Instrumental ADL) showed a mean score of 5.6 +/-
      2.4. The mean gait speed was 0.78 +/- 0.27 and 25.6% (272) of patients had a SPPB
      (Short Physical Performance Battery) score equal to or higher than 10. Dementia
      was observed in 14.9% (111) of the G.F.C population according to the CDR scale
      (CDR >=2). Eight percent (84) presented an objective state of protein-energy
      malnutrition with MNA (Mini Nutritional Assessment) score < 17 and 39.5% (414)
      were at risk of malnutrition (MNA=17-23.5). Concerning PPP, for 54.6% (603) of
      patients, we found at least one medical condition which needed a new intervention
      and for 32.8% (362) substantial therapeutic changes were recommended. A
      nutritional intervention was proposed for 61.8% (683) of patients, a physical
      activity intervention for 56.7% (624) and a social intervention for 25.7% (284).
      At the time of analysis, a one-year reassessment had been carried out for 139
      (26.7%) of patients. CONCLUSIONS: The G.F.C was developed to move geriatric
      medicine to frailty, an earlier stage of disability still reversible. Its
      particularity is that it is intended for a single target population that really
      needs preventive measures: the frail elderly screened by physicians. The
      screening undergone by physicians was really effective because 93.6% of the
      subjects who referred to this structure were frail or pre-frail according to
      Fried's classification and needed different medical interventions. The creation
      of units like the G.F.C, specialized in evaluation, management and prevention of
      disability in frail population, could be an interesting option to support general
      practitioners, promote the quality of life of older people and increase life
      expectancy without disability.

PMID- 24886730
TI  - Putting function first.

PMID- 24886731
TI  - Frailty, identification, treatment, and clinical practice.

PMID- 24886732
TI  - Frailty: successful clinical practice implementation.

PMID- 24886733
TI  - Effect of sociodemographic variables and time on food group contribution to total
      food availability in Portuguese elderly households.
AB  - OBJECTIVE: To analyze the simultaneous effects of sociodemographic variables and
      time on each food group contribution to total Portuguese elderly household food
      availability. DESIGN: Four cross sectional Portuguese Household Budget Surveys
      were used. A multivariate analysis of variance (MANOVA), using a general linear
      model (GLM), was applied to analyze the simultaneous effects of sociodemographic
      variables and time. SETTING: Portuguese population. SUBJECTS: Nationally
      representative samples of households with members aged >= 65 years were selected
      and categorized as solitary elderly female, solitary elderly male, or couple (one
      elderly female and one elderly male). Samples included 1,967 households in 1989
      1990, 2,219 households in 1994-1995, 2,533 households in 2000-2001 and 2,441
      households in 2005-2006. RESULTS: The simultaneous effects of sociodemographic
      variables and time were significant for all food groups (P<0.001). The highest
      contribution for the total household food availability was found for cereals,
      potatoes, alcoholic beverages, non-alcoholic beverages and fruits. The effects
      were large for "household food availability" and medium for "elderly household
      type", "urbanization degree", "income", "food expenses" and "eating out
      expenses". Solitary elderly male households had the highest proportion of cereals
      and alcoholic beverages, whilst solitary elderly female households had higher
      availability of milk/milk products and fruits. Households located in urban areas
      had higher contribution of milk/milk products while rural, had higher
      contribution of potatoes. CONCLUSIONS: The simultaneous effect of the studied
      variables on food group contribution to total household food availability can be
      considered when addressing dietary recommendation for providing an insight into
      the motivations associated with food purchases.

PMID- 24886734
TI  - Diet, weight, cytokines and bone health in postmenopausal women.
AB  - OBJECTIVES: To investigate diet and nutrition-related factors associated with
      bone loss in a group of postmenopausal (PM) women. Nutritional intake,
      inflammatory markers and body composition (weight, body mass index, fat/lean
      mass) were analysed for associations with bone mineral density (BMD). DESIGN: A
      cross sectional study examining correlations between BMD (Duel-energy X ray
      absorptiometry; (DXA) and dietary intake (3-day diaries), body composition and
      plasma bone and inflammatory markers: C-terminal telopeptide of type I collagen
      (CTX) and procollagen type I N propeptide (P1NP), C- reactive protein (CRP),
      interleukin 6 and 10 (IL-6, IL-10), tumour necrosis factor (TNF) and
      osteoprotegerin (OPG). SETTING: Community dwelling women from the Auckland,
      Hawke's Bay and Manawatu regions in New Zealand. PARTICIPANTS: 142 healthy, PM
      women aged 50-70 years. RESULTS: OPG (per kilogram fat mass) was increased in
      women with osteoporosis (p<0.001) compared to groups classified with normal BMD
      and osteopenia. Protein, vitamin B12, zinc, potassium and dairy intake were all
      positively correlated with higher BMD while dairy and potassium intakes also
      inversely correlated with CTX. Body composition (weight, BMI and fat/lean mass)
      had strong positive associations with BMD. Multiple regression analysis showed
      body weight, potassium and dairy intake were predictors of increased BMD in PM
      women and explained 39% (r2=0.39, p< 0.003) of variance. CONCLUSION: BMD was
      negatively correlated with OPG and positively with weight, dairy and potassium
      intake. This study highlights the importance of maintaining adequate body weight
      and emphasising dairy and potassium predominantly sourced from fruit/vegetables
      to reduce bone loss at midlife.

PMID- 24886735
TI  - Factors associated with poor nutritional status among community dwelling Lebanese
      elderly subjects living in rural areas: results of the AMEL study.
AB  - OBJECTIVES: This study aimed to assess the nutritional status, measured by MNA,
      and its association with socio-demographic indicators and health related
      characteristics of a representative sample of community dwelling elderly
      subjects. DESIGN: Cross-sectional study. SETTING: Community dwelling elderly
      individuals living in rural communities in Lebanon. PARTICIPANTS: 1200 elderly
      individuals aged 65 years or more. MEASUREMENTS: Socio-demographic indicators and
      health related characteristics were recorded during a standardized interview.
      Nutritional status was assessed through Mini Nutritional Assessment (MNA). The 5
      item GDS score and the WHO-5-A score were used to assess mood, whereas Mini
      Mental Status (MMS) was applied to evaluate cognitive status. RESULTS: The
      prevalence of malnutrition and risk of malnutrition was 8.0% respective 29.1% of
      the study sample. Malnutrition was significantly more frequent in elderly
      subjects aged more than 85 years, in females, widowed and illiterate people.
      Moreover, participants who reported lower financial status were more often
      malnourished or at risk of malnutrition. Regarding health status, poor
      nutritional status was more common among those reporting more than three chronic
      diseases, taking more than three drugs daily, suffering from chronic pain and
      those who had worse oral health status. Also, depressive disorders and cognitive
      dysfunction were significantly related to malnutrition. After multivariate
      analysis following variables remained independently associated to malnutrition:
      living in the governorate of Nabatieh (ORa 2.30, 95% CI 1.35 -3.93), reporting
      higher income (ORa 0.77, 95% CI 0.61-0.97), higher number of comorbidities (ORa
      1.22, 95% CI 1.12-1.32), chronic pain (ORa 1.72, 95% CI 1.24-2.39), and
      depressive disorders (ORa 1.66, 95% CI 1.47-1.88). On the other hand, better
      cognitive functioning was strongly associated with decreased nutritional risk
      (ORa 0.27, 95%CI 0.17-0.43). CONCLUSION: Our results highlighted the close
      relationship between health status and malnutrition. The identification of
      potential predictive factors may allow better prevention and management of
      malnutrition in elderly people.

PMID- 24886736
TI  - Long-term intake of nuts in relation to cognitive function in older women.
AB  - OBJECTIVE: Nuts contain nutrients that may benefit brain health; thus, we
      examined long-term intake of nuts in relation to cognition in older women.
      DESIGN: Population-based prospective cohort study. SETTING: Academic research
      using data from the Nurses' Health Study. PARTICIPANTS: Nut intake was assessed
      in a food-frequency questionnaire beginning in1980, and approximately every four
      years thereafter. Between 1995-2001, 16,010 women age 70 or older (mean age = 74
      years) without a history of stroke were administered 4 repeated telephone-based
      cognitive interviews over 6 years. Our final sample included 15,467 women who
      completed an initial cognitive interview and had complete information on nut
      intake. MAIN OUTCOME MEASURES: The Telephone Interview for Cognitive Status
      (TICS), a global score averaging the results of all tests (TICS, immediate and
      delayed verbal recall, category fluency, and attention), and a verbal memory
      score averaging the results of tests of verbal recall. RESULTS: In multivariable
      adjusted linear regression models, higher long-term total nut intake was
      associated with better average cognitive status for all cognitive outcomes. For
      the global composite score combining all tests, women consuming at least 5
      servings of nuts/week had higher scores than non-consumers (mean difference=0.08
      standard units, 95% confidence interval 0.00-0.15; p-trend=0.003). This mean
      difference of 0.08 is equivalent to the mean difference we find between women 2
      years apart in age. Long-term intake of nuts was not associated with rates of
      cognitive decline. CONCLUSIONS: Higher nut intake may be related to better
      overall cognition at older ages, and could be an easily-modifiable public health
      intervention.

PMID- 24886737
TI  - Percutaneous endoscopic gastrostomy (PEG) tubes are placed in elderly adults in
      Japan with advanced dementia regardless of expectation of improvement in quality
      of life.
AB  - BACKGROUND: The Japan Geriatrics Society published a guideline on the decision
      making process for health care for the elderly in June 2012, noting that
      withholding or withdrawing feeding tubes are treatment options that should be
      discussed during the decision-making process. Arguments against the guideline
      posit that the insertion of a percutaneous endoscopic gastrostomy (PEG) tube
      feeding may improve quality of life (QOL) for elderly adults and their relatives.
      OBJECTIVES: The aim of the present study was to explore (a) expected outcomes
      with PEG tube placement and (b) outcomes from PEG tube feeding in long-term care
      settings among elderly adults with advanced dementia in Japan. DESIGN: This study
      was conducted using a cross-sectional study design. SETTING: A total of 381
      hospitals and 985 long-term care facilities provided sets of completed
      questionnaires. PARTICIPANTS: There were 1 199 hospital patients and 2 160 long
      term care patients aged 65 years or older with PEG tube placement included in the
      analysis. MEASUREMENTS: The nurses or physicians at each hospital provided
      information on the level of dementia at the time of PEG tube placement and on the
      expected outcomes of PEG tube feeding for elderly hospital patients. The nurses
      or other direct care workers at each facility provided information on the level
      of dementia and outcomes from PEG tube feeding for the long-term care patients.
      RESULTS: In the hospital patient group, 62.9% of patients had advanced dementia.
      PEG tube feeding was expected to prolong survival for 51.1% of hospital patients
      with advanced dementia. Improved QOL was expected for 39.1% of them. In the long
      term care patient group, 61.7% of patients had advanced dementia. The rate of
      patients enjoying their own lives was lower in long-term care patients who had
      advanced dementia (4.2%) than in the other patients (16.4%). Approximately 60% of
      relatives reported satisfaction with the QOL of the patients, both in the long
      term care patients with advanced dementia and the other patients. CONCLUSION: Our
      results question the assumption that PEG tube feeding may improve QOL among
      elderly adults with advanced dementia. The national health policy should explore
      an approach to help patients, relatives, and practitioners make decisions about
      feeding options.

PMID- 24886739
TI  - Representation of older patients in clinical trials for drug approval in Japan.
AB  - To examine how target patients seen in clinical practice are represented in
      clinical trials for approved drugs in Japan, we compared the age distribution of
      older patients enrolled in confirmatory clinical trials for regulatory approval
      with that of the estimated actual patient population. Drugs for 6 chronic
      conditions common among older patients (diabetes mellitus, hypertension,
      rheumatoid arthritis, non-small cell lung cancer, depression and Alzheimer's
      disease) launched by 2012 in Japan were selected. The disparity in age
      distribution between patients in trials and patients seen in clinical practice
      varied depending on the disease, but older patients, especially those aged 75 or
      older, were generally underrepresented in clinical trials for regulatory approval
      in Japan. Under-representation of older patients in hypertension trials was
      particularly marked compared to other conditions, despite the similarity in age
      distribution of patients seen in clinical practice. One factor causing this
      disparity may be an upper age limit in clinical trial protocols. More effort is
      needed to properly characterize the benefits and risks of drugs for older
      patients. This should include the active enrollment of older patients in clinical
      trials, the establishment of better assessment tools such as pharmacometric
      approaches, and the appropriate planning and conducting of post-marketing surveys
      and studies. 

PMID- 24886738
TI  - The use of dietary supplements among older persons in southern Germany - results
      from the KORA-age study.
AB  - OBJECTIVES: Current population-based surveys in Europe on the prevalence of
      dietary supplement (DS) use in older individuals are scarce. The aim of the
      present study was to investigate patterns, prevalence and determinants of non
      herbal DS use in aged subjects. Furthermore, the intake amounts of vitamins and
      minerals from supplements were assessed. DESIGN: Cross-sectional. SETTING: Data
      on supplement use were available from an age- and sex-stratified random sample of
      the German population-based KORA (Cooperative Health Research in the Region of
      Augsburg)-Age study. PARTICIPANTS: 1,079 persons who were born in or before the
      year 1943. MEASUREMENTS: Use of dietary supplements and medications during the
      last seven days was recorded in a face-to-face interview in 2009. Participants
      were asked to bring all packages of ingested preparations to the study center.
      Not only vitamin/mineral supplements, but also non-vitamin non-mineral non-herbal
      supplements and drugs containing vitamins and minerals were coded as DS. RESULTS:
      The age-standardized prevalence of DS intake was 54.3% in women and 33.8% in men,
      respectively. The most commonly supplemented mineral and vitamin, respectively,
      was magnesium (31.9%) and vitamin D (21.5%) in women and magnesium (18.0%) and
      vitamin E (12.0%) in men. The highest intakes, compared to the German Dietary
      Reference Intakes, were reported for biotin, vitamin B6 and B1. Excessive intakes
      (equal or above the European Tolerable Upper Intake Levels (UL)) were observed
      especially for magnesium and vitamin E. 20.2% of the women and 32.5% of the men
      who took magnesium supplements regularly exceeded the UL for magnesium. In case
      of vitamin E this was true for 8.0% of the women and 13.6% of the men.
      Determinants of DS use were sex, education, smoking, physical activity,
      neurological diseases, and stroke. CONCLUSION: A high proportion of the general
      population aged 65 years and older in Southern Germany uses DS, especially
      supplements containing vitamins/minerals. The supplementation of vitamin D can be
      regarded as favorable in this age group, whereas the excessive intakes of vitamin
      E might be a cause of concern.

PMID- 24886740
TI  - Grape seed extract and zinc containing nutritional food supplement prevents onset
      and progression of age-related cataract in wistar rats.
AB  - OBJECTIVE: To study possible inhibition of oxidative stress and cataract
      formation by single combined formulation of grape seed extract and Zincovit
      tablets against sodium selenite-induced age-related cataract in Wistar rat pups.
      METHODS: Oxidative stress and consequent cataract formation was induced by
      subcutaneous administration of a single dose of sodium selenite (10 umoles/kg) to
      Wistar rat pups on day 7 post-natally. In experiments designed to inhibit such
      cataract formation, the pups were pretreated subcutaneously with combined
      formulation of grape seed extract and Zincovit tablets (40, 80 and 160 mg/kg),
      one day prior to the administration of selenite and continuing such treatment
      till day 20, when the experiments were terminated. The extent of tissue damage
      caused by the selenite was assessed biochemically by measurements of the levels
      of reduced glutathione, glutathione peroxidase, glucose-6-phosphate
      dehydrogenase, protein thiol, catalase, superoxide dismutase, malondialdehyde,
      aldose reductase, sorbitol dehydrogenase and adenosine triphosphate in the
      isolated lenses. Cataract formation and its prevention were monitored by
      examining the eye with pen light illumination and subsequent photography of the
      isolated lenses. RESULTS: Injection of selenite led to a significant loss of lens
      clarity due to cataract formation. In the group treated with combined formulation
      of grape seed extract and Zincovit tablets, the formation of cataract was
      significantly prevented. In the normal and selenite induced senile cataract
      control group, the levels of lens oxidative stress markers, G6PD and ATP were
      substantially lower than in the grape seed extract with Zincovit tablets treated
      group (p < 0.05). CONCLUSION: Over all, the results suggest that single combined
      formulation of grape seed extract and Zincovit tablets may offer a prophylactic
      measure against onset and progression of age- related cataract of human subjects
      as nutritional food supplement.

PMID- 24886741
TI  - Intramuscular fat and inflammation differ in older adults: the impact of frailty
      and inactivity.
AB  - OBJECTIVES: Intramuscular adipose tissue (IMAT) is recognized as a negative
      predictor of both muscle and mobility function in older adults, however the
      mechanism by which IMAT may negatively influence muscle and mobility function is
      currently unknown. The release of pro-inflammatory cytokines from IMAT provides a
      potential reason for these negative associations. To explore this hypothesis we
      compared IMAT and muscular inflammation in age-and BMI-matched older non-obese
      frail and non-frail adults. We also sought to examine the relationship between
      IMAT and inflammation, and muscle and mobility function in this group of older
      adults. DESIGN: A case-control sampling was used for this study. Age-and BMI
      matched non-obese frail and non-frail individuals (<65 years) were recruited.
      MEASUREMENTS: MRI was used to quantify thigh IMAT and lean tissue. Unilateral
      muscle biopsies were used to quantify muscular inflammation as represented by
      interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-alpha). Muscle and
      mobility function was also measured using a maximal voluntary isometric
      contraction, six-minute walk, and self-selected gait speed. PARTICIPANTS: 26
      older (80.7 +/- 5.4 years) individuals (8 frail and 18 non-frail) were enrolled.
      RESULTS: The frail-group had increased IMAT (p<0.01) and decreased lean tissue
      (p<0.01), and elevated IL-6 muscle mRNA (p=0.02) and IL-6 protein content
      (p=0.02) compared to the non-frail group. IMAT was significantly associated with
      IL-6 mRNA (r=0.43, p=.04) and protein expression within the muscle (r=0.41, p=
      0.045). IL-6 mRNA was significantly associated with six-minute walk (r=-0.63,
      p<0.01), and gait speed (r=-0.60, p <0.01) and IL-6 protein was significantly
      associated with muscle force (r=-0.54, p=0.01), six-minute walk (r=-0.66,
      p<0.01), and gait speed (r=-0.76, p<0.01). No significant relationships were
      found for any variables with TNF-a. CONCLUSION: Non-obese, older, frail
      individuals have increased IMAT and muscular inflammation when compared to their
      non-frail, age- and BMI-matched peers. A significant relationship exists between
      IMAT and muscle IL-6 expression as well as between IL-6 and muscle and mobility
      function of these older adults. This IMAT-inflammatory pathway provides a
      potential link between IMATs and decreased muscle and mobility function.

PMID- 24886743
TI  - Sarcopenia according to the european working group on sarcopenia in older people
      (EWGSOP) versus Dynapenia as a risk factor for disability in the elderly.
AB  - BACKGROUND: Sarcopenia, defined as low muscle mass (LMM), and dynapenia have been
      associated with adverse outcomes in elderly. OBJECTIVE: Contrast the association
      of sarcopenia versus dynapenia with incidence of disability. DESIGN: A four-year
      prospective study (2006-2010). SETTING: Sao Paulo, Brazil. PARTICIPANTS: 478
      individuals aged 60 and older from the Saude, Bem-Estar e Envelhecimento (SABE)
      study who were non-disabled at baseline. MEASUREMENTS: Sarcopenia, measured
      according to the European Working Group on Sarcopenia in Older People (EWGSOP),
      includes: LMM assessed by skeletal muscle mass index <=8.90kg/m2 (men) and
      <=6.37kg/m2 (women); low muscle strength (LMS) assessed by handgrip strength
      <30kg (men) and <20kg (women); and low physical performance (LPP) assessed by
      gait speed <=0.8m/s. Diagnosis of sarcopenia required LMM plus LMS or LPP.
      Dynapenia was defined as handgrip strength <30kg (men) and <20kg (women).
      Covariates included socio-demographic and behavioral variables, medical
      conditions, hospitalization, depressive symptoms, cognition, perception of
      vision, hearing and body mass index. OUTCOMES: Disability in mobility or
      instrumental activities of daily living (IADL) or disability in activities of
      daily living (ADL) and IADL. RESULTS: The incidence density of mobility or IADL
      disability was 43.4/1000 person/year and 22.6/1000 person/year for IADL and ADL
      disability. There was no significant difference in incidence density according
      sarcopenia or dynapenia status. After controlling for all covariates, sarcopenia
      was associated with mobility or IADL disability (relative risk ratio = 2.23,
      95%Confidence Interval: 1.03-4.85). Dynapenia was not associated with disability.
      CONCLUSIONS: Sarcopenia according to the EWGSOP definition can be used in
      clinical practice as a screening tool for early functional decline (mobility or
      IADL disability).

PMID- 24886742
TI  - Influence of age and gender on fat mass, fat-free mass and skeletal muscle mass
      among Australian adults: the Australian diabetes, obesity and lifestyle study
      (AusDiab).
AB  - BACKGROUND: Bioelectrical impedance (BIA) represents a simple, inexpensive and
      non-invasive method that is often used to assess fat-mass (FM) and fat-free mass
      (FFM) in large population-based cohorts. OBJECTIVE: The aim of this study was to
      describe the reference ranges and examine the influence of age and gender on FM,
      FFM and skeletal muscle mass (SMM) as well as height-adjusted estimates of FM
      [fat mass index (FMI)], FFM [fat-free mass index (FFMI)] and SMM [SMM index
      (SMI)] in a national, population-based cohort of Australian adults. DESIGN AND
      PARTICIPANTS: The analytical sample included a total of 8,582 adults aged 25-91
      years of Europid origin with complete data involved in the cross-sectional 1999
      2000 Australian, Diabetes, Obesity and Lifestyle (AusDiab) Study. MEASUREMENTS:
      Bioelectrical impedance analysis was used to examine components of body
      composition. Demographic information was derived from a household interview.
      RESULTS: For both genders, FFM, SMM and SMI decreased linearly from the age of 25
      years, with the exception that in men SMI was not related to age and FFM peaked
      at age 38 years before declining thereafter. The relative loss from peak values
      to >=75 years in FFM (6-8%) and SMM (11-15%) was similar between men and women.
      For FM and FMI, there was a curvilinear relationship with age in both genders,
      but peak values were detected 6-7 years later in women with a similar relative
      loss thereafter. For FFMI there was no change with age in men and a modest
      increase in women. CONCLUSION: In Australian adults there is heterogeneity in the
      age of onset, pattern and magnitude of changes in the different measures of
      muscle and fat mass derived from BIA, but overall the age-related losses were
      similar between men and women.

PMID- 24886744
TI  - The relationship between lean mass, muscle strength and physical ability in
      independent healthy elderly women from the community.
AB  - BACKGROUND/OBJECTIVES: The association between muscle mass, strength and physical
      performance has been established in the elderly with co-morbidities. In this
      study, lean and fat mass, bone mineral density, knee extension and flexion
      strength and physical ability tests in healthy independent elderly women were
      investigated. Main determinants of lean mass, strength and physical ability were
      determined searching for predictors of healthy aging. METHODS: A total of 100
      healthy women aged >= 65 years considered independent and active were invited.
      Bone mass and body composition were assessed by DXA. The strength of the lower
      limb was assessed by isokinetic dynamometry, and physical ability was measured
      by: Timed Up and Go (TUG), Berg Balance Test (BBT) and Dynamic Gait Index (DGI).
      RESULTS: Women were on average 70.8+/-4.92 years old, had BMI of 27.38+/-5.11
      kg/m2 and fat mass of 26.96+/-9.62 kg or 40.65+/-8.06%. Total lean mass and
      appendicular lean mass (ALM) were 35.38+/-4.83 kg and 15.32+/-2.26 kg,
      respectively, while relative skeletal mass index (RSMI) was 6.51+/-0.77 kg/m2.
      Age did not correlate significantly with ALM. Age and ALM were the main
      determinants of the strength of the lower limb (p<0.001) while age and strength
      of the lower limb were significantly associated with the performance on the
      physical tests (p<0.001). CONCLUSION: Age has a negative impact on the strength
      and the physical performance in independent healthy women without co-morbidities.
      Physical ability tests are positively influenced by the strength of the lower
      limb. These relationships suggest that muscle strength should be the parameter to
      be prioritized when preparing for healthy aging.

PMID- 24886745
TI  - Participation in a novel treatment component during residential substance use
      treatment is associated with improved outcome: a pilot study.
AB  - BACKGROUND: A person-centered substance use treatment component, the Natural
      Recovery Program, was developed. The Natural Recovery Program is comprised of
      small group therapy combined with pursuit of hobbies. METHODS: This was a pilot
      study of the program and was not randomized. A retrospective record review of 643
      veterans in an inpatient mental health recovery and rehabilitation program was
      analyzed to determine if participants of Natural Recovery had a different rate of
      treatment completion than those who elected to participate in the core program
      alone. Univariate and multivariate analyses were conducted on: participation in
      the Natural Recovery Program; co-morbid psychiatric disorders; and legal,
      medical, and psychiatric issues. RESULTS: Participation in Natural Recovery was
      significantly associated with successful treatment completion when analyzed by
      univariate analysis (p = 0.01). Other significant variables associated with
      successful completion included: no co-morbid psychiatric diagnosis, fewer prior
      suicide attempts, and no homelessness prior to admission. Binary logistic
      regression demonstrated that participation in Natural Recovery was associated
      with improved treatment completion, even when other variables were considered (p
      = 0.01). Treatment retention was longer for patients who participated in Natural
      Recovery, even if they did not complete treatment. CONCLUSIONS: The Natural
      Recovery Program was associated with improved outcomes, as measured by treatment
      retention in the first 60 days and by treatment completion. Participants of
      Natural Recovery with co-morbid psychiatric disorders completed treatment at a
      higher rate than those with co-morbid psychiatric disorders who participated in
      the core program. Patients reported high satisfaction with the program. This
      program may be a valuable adjunct to residential treatment.

PMID- 24886746
TI  - Effects of elastic modulus change in helical tubes under the influence of dynamic
      changes in curvature and torsion.
AB  - The incidence of stent late restenosis is high (Zwart et al., 2010, "Coronary
      Stent Thrombosis in the Current Era: Challenges and Opportunities for Treatment,"
      Curr. Treat. Options Cardiovasc. Med., 12(1), pp. 46-57) despite the extensive
      use of stents, and is most prevalent at the proximal and distal ends of the
      stent. Elastic modulus change in stented coronary arteries subject to the motion
      of the myocardium is not studied extensively. It is our objective to understand
      and reveal the mechanism by which changes in elastic modulus and geometry
      contribute to the generation of nonphysiological wall shear stress (WSS). Such
      adverse hemodynamic conditions could have an effect on the onset of restenosis.
      Three-dimensional (3D), spatiotemporally resolved computational fluid dynamics
      (CFD) simulations of pulsatile flow with moving wall boundaries and fluid
      structure interaction (FSI) were carried out for a helical artery with
      physiologically relevant flow parameters. To study the effect of coronary artery
      (CA) geometry change on stent elastic modulus mismatch, models where the
      curvature, torsion and both curvature and torsion change were examined. The
      elastic modulus is increased by a factor of two, five, and ten in the stented
      section for all three modes of motion. The changes in elastic modulus and
      arterial geometry cause critical variations in the local pressure and velocity
      gradients and secondary flow patterns. The pressure gradient change is 47%, with
      respect to the unstented baseline when the elastic modulus is increased to 10.
      The corresponding WSS change is 15.4%. We demonstrate that these changes are
      attributed to the production of vorticity (vorticity flux) caused by the wall
      movement and elastic modulus discontinuity. The changes in curvature dominate
      torsion changes in terms of the effects to local hemodynamics. The elastic
      modulus discontinuities along with the dynamic change in geometry affected the
      secondary flow patterns and vorticity flux, which in turn affects the WSS.

PMID- 24886749
TI  - Neoadjuvant chemotherapy in well-differentiated fetal adenocarcinoma: a case
      report.
AB  - BACKGROUND: Fetal adenocarcinoma of the lung is a rare subtype of pulmonary
      adenocarcinoma with a relative estimated incidence of 0.5% or fewer of all lung
      cancers. Because of its extreme rarity, there have been no controlled clinical
      trials investigating treatment regimens for fetal adenocarcinoma and, as a
      result, there are no guidelines for management. CASE PRESENTATION: We report a
      case of a well-differentiated fetal adenocarcinoma, which is a variant of
      pulmonary blastoma, that is a low-grade malignancy and associated with a good
      prognosis. A 29-year-old Moroccan man presented with a well-differentiated fetal
      adenocarcinoma staged T3N0M0, who received 3 cycles of neoadjuvant chemotherapy
      followed by surgery, with no recurrence at 2 years follow-up. CONCLUSION: Fetal
      adenocarcinoma is a rare suptype of adenocarcinoma. Surgical resection is the
      treatment of choice for resectable disease. The role of chemotherapy in the
      neoadjuvant setting or adjuvant setting is not well defined.

PMID- 24886747
TI  - Modelling the impact of ivermectin on River Blindness and its burden of morbidity
      and mortality in African Savannah: EpiOncho projections.
AB  - BACKGROUND: The African Programme for Onchocerciasis Control (APOC) has refocused
      its goals on the elimination of infection where possible, seemingly achievable by
      15-17 years of annual mass distribution of ivermectin in some African foci.
      Previously, APOC had focused on the elimination of onchocerciasis as a public
      health problem. Timeframes have been set by the World Health Organization, the
      London Declaration on Neglected Tropical Diseases and the World Bank to achieve
      these goals by 2020-2025. METHODS: A novel mathematical model of the dynamics of
      onchocercal disease is presented which links documented associations between
      Onchocerca volvulus infection and the prevalence and incidence of morbidity and
      mortality to model outputs from our host age- and sex-structured onchocerciasis
      transmission framework (EpiOncho). The model is calibrated for African savannah
      settings, and used to assess the impact of long-term annual mass administration
      of ivermectin on infection and ocular and skin disease and to explore how this
      depends on epidemiological and programmatic variables. RESULTS: Current
      onchocerciasis disease projections, which do not account for excess mortality of
      sighted individuals with heavy microfilarial loads, underestimate disease burden.
      Long-term annual ivermectin treatment is highly effective at reducing both the
      morbidity and mortality associated with onchocerciasis, and this result is not
      greatly influenced by treatment coverage and compliance. By contrast, impact on
      microfilarial prevalence and intensity is highly dependent on baseline
      endemicity, treatment coverage and systematic non-compliance. CONCLUSIONS: The
      goals of eliminating morbidity and infection with ivermectin alone are distinctly
      influenced by epidemiological and programmatic factors. Whilst the former goal is
      most certainly achievable, reaching the latter will strongly depend on initial
      endemicity (the higher the endemicity, the greater the magnitude of inter
      treatment transmission), advising caution when generalising the applicability of
      successful elimination outcomes to other areas. The proportion of systematic non
      compliers will become far more influential in terms of overall success in
      achieving elimination goals.

PMID- 24886748
TI  - Vorinostat positively regulates synaptic plasticity genes expression and spine
      density in HIV infected neurons: role of nicotine in progression of HIV
      associated neurocognitive disorder.
AB  - BACKGROUND: HIV-associated neurocognitive disorder (HAND) is characterized by
      development of cognitive, behavioral and motor abnormalities, and occurs in
      approximately 50% of HIV infected individuals. In the United States, the
      prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals
      compared to 20% in general population. Cognitive impairment in heavy cigarette
      smokers has been well reported. However, the synergistic effects of nicotine and
      HIV infection and the underlying mechanisms in the development of HAND are
      unknown. RESULTS: In this study, we explored the role of nicotine in the
      progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were
      infected with HIV-1 in the presence or absence of nicotine for 7 days. We
      observed significant increase in HIV infectivity in SK-N-MC treated with nicotine
      compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to
      significantly dysregulate the expression of synaptic plasticity genes and spine
      density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In
      addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted
      in HIV latency breakdown and recovery of synaptic plasticity genes expression and
      spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore,
      increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic
      translational process, was observed in HIV alone and in co-treatment with
      nicotine compared to untreated control and nicotine alone treated SK-N-MC cells.
      CONCLUSIONS: These results suggest that nicotine and HIV synergize to negatively
      regulate the synaptic plasticity gene expression and spine density and this may
      contribute to the increased risk of HAND in HIV infected smokers. Apart from
      disrupting latency, vorinostat may be a useful therapeutic to inhibit the
      negative regulatory effects on synaptic plasticity in HIV infected nicotine
      abusers.

PMID- 24886750
TI  - Scleroderma-polymyositis overlap syndrome versus idiopathic polymyositis and
      systemic sclerosis: a descriptive study on clinical features and myopathology.
AB  - INTRODUCTION: The objective was to characterize the clinical and myopathologic
      features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with
      a population of patients with systemic sclerosis (SSc) and polymyositis (PM).
      METHODS: A three-way comparison of patients with SSc-PM overlap (n = 25) with
      patients with SSc (n = 397) and PM (n = 40) on clinical and myopathologic
      features and causes of death. One neuropathologist blinded for the diagnosis
      evaluated all recent available muscle biopsies. Biopsies were scored for presence
      of inflammation, necrotic muscle fibers, rimmed vacuoles, fibrosis, and
      immunohistochemical staining. Clinical or myopathologic characteristics were
      compared by using the chi(2) test or one-way analysis of variance (ANOVA).
      RESULTS: The prevalence of SSc-PM overlap in the Nijmegen Systemic Sclerosis
      cohort was 5.9%. The mortality was 32% (eight of 25) in SSc-PM, of which half was
      related to cardiac diseases. The prevalence of pulmonary fibrosis was
      significantly increased in SSc-PM (83%) (P = 0.04) compared with SSc (49%) and PM
      (53%). SSc or myositis-specific antibodies were nearly absent in the SSc-PM
      group. In almost all biopsies (96%) of SSc-PM patients, necrotic muscle fibers
      were present, which was significantly increased compared with PM patients (P =
      0.02). CONCLUSIONS: Patients with SSc-PM have increased prevalence of pulmonary
      fibrosis and cardiac disease as the cause of death compared with patients with
      SSc and PM . In addition, we found that necrotizing muscle fibers with
      inflammation characterize SSc-PM overlap in muscle biopsies. Further research
      should focus on underlying mechanisms causing necrosis, inflammation, and
      fibrosis and their relation to pulmonary involvement and mortality in patients
      with SSc-PM overlap.

PMID- 24886751
TI  - Reanalysis of the gene expression profile in chronic pancreatitis via
      bioinformatics methods.
AB  - BACKGROUND: Diagnosis at an early stage of chronic pancreatitis (CP) is
      challenging. It has been reported that microRNAs (miRNAs) are increasingly found
      and applied as targets for the diagnosis and treatment of various cancers.
      However, to the best of our knowledge, few published papers have described the
      role of miRNAs in the diagnosis of CP. METHOD: We downloaded gene expression
      profile data from the Gene Expression Omnibus and identified differentially
      expressed genes (DEGs) between CP and normal samples of Harlan mice and Jackson
      Laboratory mice. Common DEGs were filtered out, and the semantic similarities of
      gene classes were calculated using the GOSemSim software package. The gene class
      with the highest functional consistency was selected, and then the Lists2Networks
      web-based system was used to analyse regulatory relationships between miRNAs and
      gene classes. The functional enrichment of the gene classes was assessed based on
      Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway annotation
      terms. RESULTS: A total of 405 common upregulated DEGs and 7 common downregulated
      DEGs were extracted from the two kinds of mice. Gene cluster D was selected from
      the common upregulated DEGs because it had the highest semantic similarity. miRNA
      124a (miR-124a) was found to have a significant regulatory relationship with
      cluster D, and DEGs such as CHSY1 and ABCC4 were found to be regulated by miR
      124a. The GO term of response to DNA damage stimulus and the pathway of
      Escherichia coli infection were significantly enriched in cluster D. CONCLUSION:
      DNA damage and E. coli infection might play important roles in CP pathogenesis.
      In addition, miR-124a might be a potential target for the diagnosis and treatment
      of CP.

PMID- 24886752
TI  - What causes environmental inequalities and related health effects? An analysis of
      evolving concepts.
AB  - Early environmental justice studies were exposure-oriented, lacked an integrated
      approach, and did not address the health impact of environmental inequalities. A
      coherent conceptual framework, needed to understand and tackle environmental
      inequalities and the related health effects, was lacking. We analyzed the more
      recent environmental justice literature to find out how conceptual insights have
      evolved. The conceptual framework of the WHO Commission on Social Determinants of
      Health (CSDH) was analyzed for additional explanations for environmental
      inequalities and the related health effects. This paper points out that recent
      environmental justice studies have broadened their scope by incorporating a
      broader set of physical and social environmental indicators, and by focusing on
      different geographic levels and on health impacts of environmental inequalities.
      The CSDH framework provided additional elements such as the role of structural
      determinants, the role of health-related behavior in relation to the physical and
      social environment, access to health care, as well as the life course
      perspective. Incorporating elements of the CSDH framework into existing
      environmental justice concepts, and performing more empirical research on the
      interactions between the different determinants at different geographical levels
      would further improve our understanding of environmental inequalities and their
      health effects and offer new opportunities for policy action. 

PMID- 24886753
TI  - Lifestyle practices and obesity in Malaysian adolescents.
AB  - AIM: To determine the influence of physical activity (PA) and sedentary behavior
      (SB) on obesity profiles of 454 Malaysian adolescents aged 12 to 19. METHODS:
      Validated PA and SB questionnaires were used and body composition assessed using
      anthropometry and dual-energy X-ray absorptiometry (DXA). RESULTS: Gender
      specific multivariate analyses showed boys with high levels of total PA and
      moderate-to-vigorous physical activity (MVPA) exhibited significantly lower
      levels of total body fat, percent body fat and android fat mass compared with low
      PA and MVPA groups, after adjusting for potential confounders. Girls with high SB
      levels showed significantly higher BMI, waist circumference and DXA-derived body
      fat indices than those at lower SB level. Multiple logistic analyses indicated
      that boys with low levels of total PA and MVPA had significantly greater obesity
      risk, 3.0 (OR 3.0; 95% CI, 1.1-8.1; p < 0.05) and 3.8-fold (OR 3.8; 95% CI, 1.4
      10.1; p < 0.01), respectively, than more active boys. Only in girls with high SB
      level was there a significantly increased risk of obesity, 2.9 times higher than
      girls at low SP levels (OR 2.8; 95% CI, 1.0-7.5; p < 0.05).   CONCLUSIONS: The
      present findings indicate that higher PA duration and intensity reduced body fat
      and obesity risk while high screen-based sedentary behaviors significantly
      adversely influenced body fat mass, particularly amongst girls when the PA level
      was low.

PMID- 24886754
TI  - Sudomotor function as a tool for cardiorespiratory fitness level evaluation:
      comparison with maximal exercise capacity.
AB  - Physical inactivity is a modifiable risk factor for cardiovascular (CV) and
      metabolic disorders. VO2max is the best method to assess cardio-respiratory
      fitness level but it is poorly adopted in clinical practice. Sudomotor
      dysfunction may develop early in metabolic diseases. This study aimed at
      comparing established CV risk evaluation techniques with SUDOSCAN; a quick and
      non-invasive method to assess sudomotor function. A questionnaire was filled-in;
      physical examination and VO2max estimation using a maximal test on a bicycle
      ergometer were performed on active Finish workers. Hand and foot electrochemical
      skin conductance (ESC) were measured to assess sudomotor function. Subjects with
      the lowest fitness level were involved in a 12 month training program with
      recording of their weekly physical activity and a final fitness level evaluation.
      Significant differences in BMI; waist and body fat were seen according to
      SUDOSCAN risk score classification. Correlation between the risk score and
      estimated VO2max was r = -0.57, p < 0.0001 for women and -0.48, p < 0.0001 for
      men. A significant increase in estimated VO2max, in hand and foot ESC and in risk
      score was observed after lifestyle intervention and was more important in
      subjects with the highest weekly activity. SUDOSCAN could be used to assess
      cardio-metabolic disease risk status in a working population and to follow
      individual lifestyle interventions. 

PMID- 24886755
TI  - Walkability is only part of the story: walking for transportation in Stuttgart,
      Germany.
AB  - In modern Western societies people often lead inactive and sedentary lifestyles,
      even though there is no doubt that physical activity and health are related. From
      an urban planning point of view it would be highly desirable to develop built
      environments in a way that supports people in leading more active and healthy
      lifestyles. Within this context there are several methods, predominantly used in
      the US, to measure the suitability of built environments for walking and cycling.
      Empirical studies show that people living in highly walkable areas are more
      physically active (for example, walk more or cycle more). The question is,
      however, whether these results are also valid for European cities given their
      different urban planning characteristics and infrastructure standards. To answer
      this question we used the Walkability-Index and the Walk Score to empirically
      investigate the associations between walkability and active transportation in the
      city of Stuttgart, Germany. In a sample of household survey data (n = 1.871) we
      found a noticeable relationship between walkability and active transportation-the
      more walkable an area was, the more active residents were. Although the
      statistical effect is small, the health impact might be of relevance. Being
      physically active is multi-determined and not only affected by the walkability of
      an area. We highlight these points with an excursion into research that the
      health and exercise sciences contribute to the topic. We propose to strengthen
      interdisciplinary research between the disciplines and to specifically collect
      data that captures the influence of the environment on physical activity in the
      future. 

PMID- 24886756
TI  - What works in community-based interventions promoting physical activity and
      healthy eating? A review of reviews.
AB  - Chronic diseases, such as type II diabetes, are on the rise worldwide. There is
      consistent evidence that physical activity and healthy eating are important
      lifestyle factors which affect the risk for chronic diseases. Community-based
      interventions are of particular public health interest as they reach target
      groups in their natural living environment and may thus achieve high population
      level impacts. We conducted a systematic literature search to assess the
      effectiveness of community-based interventions to promote physical activity and
      healthy eating. Specifically, we searched for promising intervention strategies
      in this setting. We narratively summarized the results of 18 systematic reviews.
      Among children and adolescents, we found moderate evidence for effects on weight
      change in primary school-aged children for interventions containing a school
      component. The evidence for interventions aimed at general adult populations was
      inconclusive. Self-monitoring, group-based components, and motivational signs to
      encourage stair use were identified as promising strategies to increase physical
      activity. Among adults at risk for type II diabetes, evidence was found for
      beneficial effects on weight change and diabetes incidence. However,
      interventions for this group were not integrated in more comprehensive community
      based approaches. 

PMID- 24886757
TI  - Drinking water management: health risk perceptions and choices in First Nations
      and non-First Nations communities in Canada.
AB  - The relationship between tap water and health has been a topic of public concern
      and calls for better management in Canada since well-publicized contamination
      events in two provinces (Ontario and Saskatchewan) in 2000-2001. This study
      reports the perspectives on health risks from tap water and corresponding use of,
      and spending on, bottled water in a number of different communities in Canada. In
      2009-2010, four First Nations communities (three from Ontario and one from
      Saskatchewan) and a geographically diverse sample of non-First Nations Canadians
      were surveyed about their beliefs concerning health risks from tap water and
      their spending practices for bottled water as a substitute. Responses to five
      identical questions were examined, revealing that survey respondents from Ontario
      First Nations communities were more likely than non-First Nations Canadians to
      believe bottled water is safer than tap water (OR 1.6); more likely to report
      someone became ill from tap water (OR 3.6); more likely to express water and
      health concerns related to tap water consumption (OR 2.4); and more likely to
      spend more on bottled water (OR 4.9). On the other hand, participants from one
      Saskatchewan First Nations community were less likely than non-First Nations
      Canadians to believe that someone had become ill from drinking tap water (OR
      3.8), less likely to believe bottled water is safer than tap (OR 2.0), and less
      likely to have health concerns with tap water (OR 1.5). These differences,
      however, did not translate into differences in the likelihood of high bottled
      water expenditures or being a 100% bottled water consumer. The paper discusses
      how the differences observed may be related to water supply and regulation,
      trust, perceived control, cultural background, location, and past experience. 

PMID- 24886758
TI  - The ethical dimension in published animal research in critical care: the dark
      side of our moon.
AB  - The replacement, refinement, and reduction (3Rs) guidelines are the cornerstone
      of animal welfare practice for medical research. Nowadays, no animal research can
      be performed without being approved by an animal ethics committee. Therefore, we
      should expect that any published article would respect and promote the highest
      standard of animal welfare. However, in the previous issue of Critical Care, Bara
      and Joffe reported an unexpected finding: animal welfare is extremely poorly
      reported in critical care research publications involving animal models.This may
      have a significant negative impact on the reliability of the results and on
      future funding for our research.The ability of septic shock animal models to
      translate into clinical studies has been a challenge. Therefore, every means to
      improve the quality of these models should be pursued. Animal welfare issues
      should be seen as an additional benefit to achieve this goal. It is therefore
      critical to draw conclusions from this study to improve the standard of animal
      welfare in critical care research. This has already been achieved in other fields
      of research, and we should follow their example.

PMID- 24886759
TI  - Upper eyelid tarsoconjunctival flap for the treatment of Ahmed valve plate
      exposure.
AB  - PURPOSE: The aim of this study was to describe a new technique for the treatment
      of Ahmed valve plate exposure used in a patient with recurrent valvular plate
      exposure. BACKGROUND: An important complication of glaucoma drainage devices is
      its exposure. The treatment options reported include the use of different grafts
      covered by mucosa or conjunctiva. Despite these treatments many valves reexpose,
      especially in patients with previously damaged conjunctiva. METHODS: We report
      the case of a patient with Acanthamoeba keratitis and secondary angle closure
      glaucoma, who underwent a penetrating keratoplasty and an Ahmed valve
      implantation, and presented with repeated valvular plate exposure. After
      consecutive unsuccessful coverage methods, a novel use of a tarsoconjunctival
      flap was performed to solve this complication. CONCLUSIONS: Upper eyelid
      tarsoconjunctival flap is a useful option to cover exposed valvular plates in
      patients where traditional methods have failed.

PMID- 24886760
TI  - Steroids versus dietary therapy for the treatment of eosinophilic esophagitis.
AB  - PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is a condition characterized by
      dense mucosal eosinophilia in conjunction with symptoms of esophageal
      dysfunction. Since both the incidence and prevalence of EoE are on the rise in
      both children and adults, understanding the various treatment options available
      is imperative in choosing the proper treatment for each patient. This article
      will highlight the major strides in both medical and dietary treatment of EoE in
      the past year. RECENT FINDINGS: Whereas prior studies have shown that medical
      therapy with topical corticosteroids is effective in treating EoE, this more
      recent literature highlights some of the limitations of this approach, raising
      awareness that development of better drug delivery models is greatly needed. The
      review also describes the recent advances in the field of dietary therapy for
      this disease, particularly in adults, and further supports the notion that the
      pathophysiology of this disease in children and adults is similar, with food
      antigens driving this disease. SUMMARY: Both medical and dietary therapy are
      effective for treating adults and children with EoE. Choosing the optimal
      treatment approach should be individualized based both on patient goals and on
      available local resources. Future prospective clinical trials comparing these two
      treatment modalities are needed to help understand comparable effectiveness as
      well as to help understand potential predictors of response to treatment and
      identify optimal therapeutic endpoints.

PMID- 24886761
TI  - Resistive switching and its suppression in Pt/Nb:SrTiO3 junctions.
AB  - Oxide-based resistive switching devices are promising candidates for new memory
      and computing technologies. Poor understanding of the defect-based mechanisms
      that give rise to resistive switching is a major impediment for engineering
      reliable and reproducible devices. Here we identify an unintentional interface
      layer as the origin of resistive switching in Pt/Nb:SrTiO3 junctions. We clarify
      the microscopic mechanisms by which the interface layer controls the resistive
      switching. We show that appropriate interface processing can eliminate this
      contribution. These findings are an important step towards engineering more
      reliable resistive switching devices. 

PMID- 24886762
TI  - Circulating cytokines in predicting development of severe acute pancreatitis.
AB  - INTRODUCTION: Severe acute pancreatitis (AP) is associated with high morbidity
      and mortality. Early prediction of severe AP is needed to improve patient
      outcomes. The aim of the present study was to find novel cytokines or
      combinations of cytokines that can be used for the early identification of
      patients with AP at risk for severe disease. METHODS: We performed a prospective
      study of 163 nonconsecutive patients with AP, of whom 25 had severe AP according
      to the revised Atlanta criteria. Admission serum levels of 48 cytokines and
      growth factors were determined using Bio-Plex Pro Human Cytokine Assay 21-plex
      and 27-plex magnetic bead suspension panels. Admission plasma levels of C
      reactive protein (CRP), creatinine and calcium were measured for comparison. In
      subgroup analyses, we assessed the cytokine profiles of patients with severe AP
      (n = 14) who did not have organ dysfunction (OD) upon admission (modified
      Marshall score <2). RESULTS: Of 14 cytokines elevated in the severe AP group,
      interleukin 6 (IL-6) and hepatocyte growth factor (HGF) levels were independent
      prognostic markers of severe AP. IL-6, HGF and a combination of them predicted
      severe AP with sensitivities of 56.0%, 60.0% and 72.0%, respectively, and
      specificities of 90.6%, 92.8% and 89.9%, respectively. The corresponding positive
      likelihood ratio (LR+) values were 5.9, 8.3 and 7.1, respectively. The predictive
      values of CRP, creatinine and calcium were comparable to those of the cytokines.
      In subgroup analyses of patients with severe AP and without OD upon admission, we
      found that IL-8, HGF and granulocyte colony-stimulating factor (G-CSF) levels
      predicted the development of severe AP, with G-CSF being the most accurate
      cytokine at a sensitivity of 35.7%, a specificity of 96.1% and a LR+ of 9.1.
      CONCLUSIONS: IL-6 and HGF levels upon admission have prognostic value for severe
      AP which is similar to levels of CRP, creatinine and calcium. Although IL-6 and
      HGF, as either single or combined markers, were not perfect in identifying
      patients at risk for severe AP, the possibility that combining them with novel
      prognostic markers other than cytokines might improve prognostic accuracy needs
      to be studied. The accuracy of IL-8, HGF and G-CSF levels in predicting severe AP
      in patients without clinical signs of OD upon admission warrants larger studies.

PMID- 24886764
TI  - Targeting autoimmunity: strategies and tactics.

PMID- 24886763
TI  - Prevalence and risk factors of Strongyloides stercoralis in Takeo Province,
      Cambodia.
AB  - BACKGROUND: The threadworm Strongyloides stercoralis, the most neglected
      helminth, affects an estimated 30-100 million people worldwide. Information on S.
      stercoralis infection is scarce in tropical and sub-tropical resource poor
      countries, including Cambodia. We determined S. stercoralis infection prevalence
      and risk factors for infection in the general population in Southern Cambodia.
      METHODS: A cross-sectional study was carried out between January and April 2011
      among 2,861 participants living in 60 villages of Takeo province, using Koga-agar
      plate culture, the Baermann technique and the Kato-Katz technique on a single
      stool sample. RESULTS: Eight intestinal helminth species were diagnosed. Hookworm
      (31.4%) and S. stercoralis (21.0%) occurred most frequently. Prevalence of S.
      stercoralis infection increased with age. In all age groups a higher prevalence
      was found among males than among females (OR: 1.7; 95% CI: 1.4 - 2.0; P < 0.001).
      Participants who had a latrine at home were significantly less frequently
      infected with S. stercoralis than those who did not (OR: 0.7; 95% CI: 0.4 - 0.8;
      P = 0.003). Muscle pain (OR: 1.3; 95% CI: 1.0 - 1.6; P = 0.028) and urticaria
      (OR: 1.4; 95% CI: 1.1 - 1.8; P = 0.001) were significantly associated with S.
      stercoralis infection. CONCLUSIONS: S. stercoralis is highly prevalent among the
      general Cambodian population and should no longer be neglected. Access to
      adequate diagnosis and treatment is urgently needed.

PMID- 24886765
TI  - Novel or expanding current targets in fibrinolysis.
AB  - Globally the leading cause of long-term disability and mortality stems from
      cardiovascular diseases, which creates an enormous economic burden. Currently
      available treatments for intravascular thrombosis consist of a large repertoire
      of antithrombotic agents targeting coagulation and platelet function. However,
      the only agents available to enhance fibrinolysis are recombinant or modified
      forms of plasminogen activators. Their clinical use is limited by low efficacy,
      life-threatening side-effects (primarily caused by the high systemic dose
      required) and the inapplicability for prophylactic use. This review provides an
      update on the latest advances in targeting the antifibrinolytic proteins,
      plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis
      inhibitor, and will highlight novel therapeutic avenues to enhance fibrinolysis. 

PMID- 24886767
TI  - Call for the use of a common equation for glomerular filtration rate estimation
      in East and South-East Asia.
AB  - BACKGROUND: Estimated glomerular filtration rate (eGFR) is currently calculated
      using various equations and serum creatinine (Scr) value measured by different
      assays. Differences among these eGFRs deserve further study. METHODS: Volunteers
      from eight Asian regions (n=3283; age 20-65 years, 1454 men, 1829 women) were
      recruited. The Chronic Kidney Disease Epidemiology Collaboration equation (EPI),
      Modification of Diet in Renal Disease Study equation (MDRD) for Japanese
      (MDRDJap) and MDRD for Chinese (MDRDChi) were selected. Jaffe and enzymatic
      assays were used to measure Scr. Six eGFRs were obtained for each volunteer: EPI
      equation using Scr value of enzymatic assay (EPI/E) and Jaffe assay (EPI/J);
      MDRDJap equation using Scr value of the two assays (MDRDJap/E, MDRDJap/J); and
      MDRDChi equation using Scr value of the two assays (MDRDChi/E, MDRDChi/J).
      RESULTS: Neither Scr nor eGFR showed significant regional difference. We compared
      eGFR calculated using the same equation but with different assays. The medians
      (2.5%, 97.5%) of eGFR difference were 2.0 (-7, 14) mL/min/1.73 m(2) for EPI, 3.0
      (-12.0, 18.0) mL/min/1.73 m(2) for MDRDJap, and 5.0 (-18, 30) mL/min/1.73 m(2)
      for MDRDChi. We also compared eGFR calculated using different equations but with
      the same assay. The medians (2.5%, 97.5%) of eGFR difference were 11 (-6, 56)
      mL/min/1.73 m(2) between MDRDChi/E and EPI/E; 26 (9, 35) mL/min/1.73 m(2) between
      EPI/E and MDRDJap/E; and 39 (22, 65) mL/min/1.73 m(2) between MDRDChi/E and
      MDRDJap/E, respectively. CONCLUSIONS: eGFR difference caused by using different
      equations is much larger than that caused by using different Scr assays. A common
      equation for GFR estimation is encouraged for use in Asians.

PMID- 24886766
TI  - Factor XI as a target for antithrombotic therapy.
AB  - Anticoagulants currently used in clinical practice to treat thromboembolic
      disorders are effective but increase the risk of severe bleeding because they
      target proteins that are essential for normal coagulation (hemostasis). Drugs
      with better safety profiles are required for prevention and treatment of
      thromboembolic disease. Coagulation factor XIa has emerged as a novel target for
      safer anticoagulant therapy because of its role in thrombosis and its relatively
      small contribution to hemostasis. 

PMID- 24886768
TI  - Newborn screening for metabolic diseases: saving children's lives and improving
      outcomes.
AB  - Newborn screening for metabolic diseases was initially introduced in the 1960s
      with a program for the early diagnosis of phenylketonuria. Guidelines for the
      introduction of additional conditions to the screen required that the condition
      was sufficiently common to merit screening, that it was treatable and that the
      cost of diagnosis was not prohibitive. Additional conditions added to the screen
      included congenital hypothyroidism and congenital adrenal hyperplasia. The
      recognition of medium-chain acyl0CoA dehydrogenase deficiency coupled to the
      advent of tandem mass spectrometry as a diagnostic tool allowed for the inclusion
      of many more conditions into screening programs, some of which do not fit the
      original criteria for inclusion. This presentation will discuss the current state
      of newborn screening for metabolic diseases and report on clinical outcome
      measures of patients identified by screening. 

PMID- 24886769
TI  - Laboratory critical values: automated notification supports effective clinical
      decision making.
AB  - OBJECTIVE: Failure to adequately communicate a laboratory critical value (CV) is
      a potential cause of adverse events. The harmonization of CV reporting is
      increasingly recognized as a key issue in ensuring patient care and minimizing
      harm. With ongoing improvements in CV reporting, the patient's outcome should be
      audited to assess the effectiveness of CV notification. DESIGN AND METHODS: We
      report the data audited throughout a six month-period during which an analysis
      was made of CVs, and we describe the approach of clinicians and general
      practitioners (GPs), and their decision making following CV reporting. RESULTS:
      CV notification led to a change of treatment in 98.0% of patients admitted to
      surgical and in 90.6% of those admitted to medical wards. Clinicians made a
      further evaluation of new complications in patients in 70.0% and 60.4% of cases,
      in surgical and medical wards respectively. In more than 40.0% of cases, CVs were
      unexpected findings. In the primary care setting, critical hyperkalemia was
      managed by GPs in 55% of patients, thus sparing patient's hospitalization. For
      all outpatients with critical INR (international normalized ratio), the GPs
      changed or stopped warfarin dosage. Twenty-four percent of patients were checked
      for an additional INR, whereas a further medical examination by a consultant in
      the hospital setting was requested for 5% of patients. CONCLUSIONS: The
      laboratory plays a key role in ensuring patient safety, especially in CV
      reporting. An evaluation should be made of the patient's outcome and clinical
      decision making in order to assess the effectiveness of the CV process.

PMID- 24886770
TI  - Improved glomerular filtration rate estimation using new equations combined with
      standardized cystatin C and creatinine in Chinese adult chronic kidney disease
      patients.
AB  - OBJECTIVES: The newly developed glomerular filtration rate (GFR)-estimating
      equations developed by the CKD-EPI Collaboration and Feng et al. (2013) that are
      based on standardized serum cystatin C (ScysC), combined/not combined with serum
      creatinine (Scr), require further validation in China. We compared the
      performance of four new equations (CKD-EPIcys, CKD-EPIcr-cys, Fengcys, and Fengcr
      cys equations) with the CKD-EPI creatinine equation (CKD-EPIcr) in adult Chinese
      chronic kidney disease (CKD) patients to clarify their clinical application.
      DESIGN AND METHODS: GFR was measured using the dual plasma sampling (99m)Tc-DTPA
      method (mGFR) in 252 adult CKD patients enrolled from four centres. Scr and ScysC
      were measured by standardized assays in a central laboratory. Each equation's
      performance was assessed using bias, precision, accuracy, agreement, and correct
      classification of the CKD stage. RESULTS: The measured GFR was 46 [25-83] mL/min
      per 1.73 m(2). The CKD-EPIcys, CKD-EPIcr-cys and Fengcys equations provided
      significantly higher accuracy (P15: 38.9%, 39.7%, and 38.9%) than the CKD-EPIcr
      equation (29.8%). The CKD-EPIcr-cys and Fengcr-cys equations presented higher
      precision (IQR of the difference, 16.4 and 17.3 mL/min per 1.73 m(2),
      respectively) and narrower acceptable limits in Bland-Altman analysis (56.6 and
      50.8 mL/min per 1.73 m(2), respectively) than single marker-based equations. The
      CKD-EPIcr-cys equation achieved the highest overall correct proportion (61.5%) in
      classification of CKD stages. CONCLUSIONS: Combining ScysC and Scr measurements
      for GFR estimation improves diagnostic performance. The Scr-ScysC equation showed
      better performance than equations based on either marker alone. The CKD-EPIcr-cys
      equation showed the best performance for GFR estimation in Chinese adult CKD
      patients.

PMID- 24886771
TI  - Determination of duloxetine in human plasma with proven lack of influence of the
      major metabolite 4-hydroxyduloxetine.
AB  - OBJECTIVES: Minimizing the impact of major or unstable metabolites on the
      determination of a drug substance represents a leading task in the development
      and validation of bioanalytical methods. "Incurred samples reanalysis" provides
      relevant information too late; therefore, carefully selected tests on known
      metabolites should precede the pharmacokinetic studies. DESIGN AND METHODS: This
      paper describes a simple and rapid HPLC-UV method for the determination of
      duloxetine, a potent serotonin and norepinephrine reuptake inhibitor, in the
      presence of its major metabolite, i.e. 4-hydroxyduloxetine glucuronide. Analyte
      and fluoxetine (internal standard) were extracted from human plasma by liquid
      liquid extraction. RESULTS: No influence of the major metabolite was observed on
      the reliability of the new method. There was also lack of evidence of the major
      metabolite back-conversion to the parent drug substance. The validation
      demonstrated high precision of the new method. All validation parameters met the
      acceptance criteria of bioanalytical regulations. CONCLUSIONS: The new method
      enabled the reliable determination of duloxetine in the presence of its major
      metabolite in the human plasma. The method might be applied to pharmacokinetic
      studies in humans, including bioequivalence and therapeutic drug monitoring.

PMID- 24886773
TI  - NET gains and losses: the role of changing nuclear envelope proteomes in genome
      regulation.
AB  - In recent years, our view of the nucleus has changed considerably with an
      increased awareness of the roles dynamic higher order chromatin structure and
      nuclear organization play in nuclear function. More recently, proteomics
      approaches have identified differential expression of nuclear lamina and nuclear
      envelope transmembrane (NET) proteins. Many NETs have been implicated in a range
      of developmental disorders as well as cell-type specific biological processes,
      including genome organization and nuclear morphology. While further studies are
      needed, it is clear that the differential nuclear envelope proteome contributes
      to cell-type specific nuclear identity and functions. This review discusses the
      importance of proteome diversity at the nuclear periphery and highlights the
      putative roles of NET proteins, with a focus on nuclear architecture.

PMID- 24886774
TI  - Lawsonia inermis L. (henna): ethnobotanical, phytochemical and pharmacological
      aspects.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The use of Lawsonia inermis L. (henna) for
      medicinal and cosmetic purposes is inextricably linked to ancient and modern
      cultures of North Africa and Asia. Literature and artwork indicates that Lawsonia
      inermis played an important holistic role in the daily lives of some ancient
      cultures, providing psychological and medicinal benefits, as well as being used
      for personal adornment. Although henna was historically applied to the hands and
      feet to protect against fungal pathogens and to hair to combat lice and dandruff,
      other traditional uses include the treatment of liver and digestive disorders,
      reduction of tissue loss in leprosy, diabetic foot disorders and ulcers.
      PHYTOCHEMISTRY: Almost 70 phenolic compounds have been isolated from various
      parts of the plant. Naphthaquinones, which include the dyeing principle lawsone,
      have been linked to many of the pharmacological activities. The terpene, beta
      ionone is largely responsible for the pungent odour of the essential oil isolated
      from the flowers. In addition to other volatile terpenes, some non-volatile
      terpenoids, a single sterol, two alkaloids and two dioxin derivatives have also
      been isolated from the plant. BIOACTIVITY: Henna is a pharmacologically important
      plant with significant in vitro and in vivo biological activities. Although a
      myriad of pharmacological activities have been documented, the antioxidant and
      antimicrobial activities are the most thoroughly investigated. Some incidents of
      adverse reactions following application to the skin have been reported, but these
      are mainly confined to cases involving individuals with glucose-6-phosphate
      dehydrogenase deficiency and reactions to adulterants added to henna products.
      CONCLUSIONS: Adulteration of henna is very common and may have resulted in
      unwarranted scientific findings. Phytochemical profiling studies of the plant,
      which are crucial for the establishment of proper quality control protocols, are
      lacking and hamper the development of medicinal products. Although many in vitro
      studies have been conducted to evaluate the pharmacological activities and many
      in vivo studies have focussed on the toxicity of extracts, more in vivo studies
      to validate pharmacological activities are needed. The roles of specific
      compounds and their synergies have not been comprehensively investigated.

PMID- 24886772
TI  - Electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy in
      multiple myeloma: a feasibility study.
AB  - BACKGROUND: This single-arm study evaluated feasibility, safety, and initial
      efficacy of electroacupuncture for thalidomide/bortezomib-induced peripheral
      neuropathy (PN) in cancer patients with multiple myeloma. METHODS: Patients with
      neuropathy >= grade 2 received 20 acupuncture treatments over 9 weeks. RESULTS:
      For the 19 evaluable patients, Functional Assessment of Cancer
      Therapy/Gynecological Oncology Group-Neurotoxicity (FACT/GOG/NTX) mean (SD)
      scores improved significantly between baseline and week 13 (20.8 [9.6] vs 13.2
      [8.5], p = 0.0002). Moderate effect size differences began on week 4, with the
      largest effect size differences found at week 9 for FACT/GOG/NTX scores, worst
      pain in the last 24 hours, and pain severity (Cohen's d = 1.43, 1.19, and 1.08,
      respectively) and continuing through week 13 (Cohen's d = 0.86, 0.88, and 0.90,
      respectively). From baseline to week 13, additional significant improvements were
      seen as follows: postural stability (1.0 [0.6] vs 0.8 [0.4], p = 0.02); coin test
      (10.0 [7.4] vs 5.6 [1.9], p < 0.0001); button test (96.1 [144.4] vs 54.9 [47.3],
      p < 0.0001); and walking test (21.6 [10.0] vs 17.2 [7.7], p = 0.0003). No
      significant changes were seen with NCS. CONCLUSIONS: Acupuncture may help
      patients experiencing thalidomide- or bortezomib-induced PN. Larger, randomized,
      clinical trials are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT00891618.

PMID- 24886776
TI  - Somatotopy of the extrinsic laryngeal muscles in the human sensorimotor cortex.
AB  - The larynx is the major organ of vocalization. The intrinsic laryngeal muscles
      modify the internal shape of the larynx while the extrinsic laryngeal muscles
      move the entire larynx vertically in the airway. Previous neuroimaging research
      has established the somatotopic location of the intrinsic musculature of the
      larynx in the human motor cortex and showed it to be in an evolutionarily novel
      location compared to the homologous region in monkey cortex. In the current
      study, we attempted for the first time to determine the somatotopic localization
      of the extrinsic laryngeal musculature in humans. In a functional magnetic
      resonance imaging experiment, we had participants voluntarily move their larynx
      upward and/or downward in the airway in the absence of vocalization to engage the
      extrinsic laryngeal muscles or vocalize in the absence of vertical laryngeal
      movement to engage the intrinsic laryngeal muscles. Vertical movement of the
      larynx activated ventral pericentral sensorimotor cortex extending dorsally to
      overlap with the representation of the intrinsic laryngeal muscles. This pattern
      is a reversal from the somatotopy of the monkey, where the extrinsic laryngeal
      muscles are represented dorsally to the intrinsic laryngeal muscles. 

PMID- 24886777
TI  - Volumetrics relate to the development of depression after traumatic brain injury.
AB  - Previous research suggests that many people who sustain a traumatic brain injury
      (TBI), even of the mild form, will develop major depression (MD). We previously
      reported white matter integrity differences between those who did and did not
      develop MD after mild TBI. In this current paper, we aimed to investigate whether
      there were also volumetric differences between these groups, as suggested by
      previous volumetric studies in mild TBI populations. A sample of TBI-with-MD
      subjects (N=14), TBI-without-MD subjects (N=12), MD-without-TBI (N=26) and
      control subjects (no TBI or MD, N=23), received structural MRI brain scans. T1
      weighted data were analysed using the Freesurfer software package which produces
      automated volumetric results. The findings of this study indicate that (1) TBI
      patients who develop MD have reduced volume in temporal, parietal and lingual
      regions compared to TBI patients who do not develop MD, and (2) MD patients with
      a history of TBI have decreased volume in the temporal region compared to those
      who had MD but without a history of TBI. We also found that more severe MD in
      those with TBI-with-MD significantly correlated with reduced volume in anterior
      cingulate, temporal lobe and insula. These findings suggest that volumetric
      reduction to specific regions, including parietal, temporal and occipital lobes,
      after a mild TBI may underlie the susceptibility of these patients developing
      major depression, in addition to altered white matter integrity. 

PMID- 24886775
TI  - Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background.
AB  - Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1
      gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes,
      and have been used as a major pre-clinical model for FXS. Although FXS occurs in
      both male and female patients, most studies on the mouse model use male animals.
      Few studies test whether gender affects the face validity of the mouse model.
      Here, we examined multiple behavioral phenotypes with male hemizygous and female
      homozygous Fmr1 KO mice on C57BL/6 background. For each behavioral paradigm, we
      examined multiple cohorts from different litters. We found that both male and
      female Fmr1 KO mice displayed significant audiogenic seizures, hyperactivity in
      the open field test, deficits in passive avoidance and contextual fear memory,
      and significant enhancement of PPI at low stimulus intensity. Male and female
      Fmr1 KO mice also showed more transitional movement between the lit and dark
      chambers in the light-dark tests. The lack of gender effects suggests that the
      Fmr1 KO mouse is a reasonable tool to test the efficacy of potential FXS
      therapies. 

PMID- 24886778
TI  - Activation of the olfactory system in response to male odors in female
      prepubertal mice.
AB  - Exposure to male odors during the prepubertal period accelerates puberty, a
      phenomenon known as the Vandenbergh effect. This experiment identifies the parts
      of the olfactory pathway that respond to male odors in prepubertal female mice.
      Female mice were kept in a room free of adult male odors from birth until odor
      exposure. At post-natal day 21, 24 or 28, (ages representing time points early,
      intermediate, and late in the prepubertal period) mice were exposed to clean
      bedding, soiled bedding from castrated males, or soiled bedding from intact
      males. Each group was exposed to odor in separate rooms to prevent cross
      contamination. Ninety minutes after odor exposure, mice were sacrificed, the
      brains removed and prepared for c-Fos immunohistochemistry. The numbers of
      neurons expressing c-Fos were counted in a defined area of the following nuclei:
      AOB mitral layer, AOB granular layer, MOB, MEPV, MEPD, Aco, BNST, MPOA, and VMH.
      There was a significant effect of age on c-Fos-expression in the MEPV, MEPD, Aco,
      MPOA, BNST and piriform cortex. There was a significant effect of odor on c-Fos
      expression in the MEPV, MEPD, Aco, MPOA, and VMH, showing that these areas are
      differentially sensitive to intact male odors vs. clean bedding and that these
      brain areas may be responsible for communicating odor information that drives
      puberty acceleration.

PMID- 24886779
TI  - Dexamethasone suppresses the locomotor response of neonatal rats to novel
      environment.
AB  - Locomotion of animals in the novel environment is determined by two main factors
      the intrinsic motor activity and the specific locomotor response to novelty.
      Glucocorticoids alter neurobehavioral development of mammals and its locomotor
      manifestations. However, it remains unclear whether the intrinsic and/or the
      novelty-induced activity are affected by glucocorticoids during early life. Here,
      the principal component analysis was used to determine the main factors that
      underlie alterations in locomotion of rat pups treated with dexamethasone. It was
      shown that neonatal rats exhibited an enhanced locomotion in the novel
      environment beginning from postnatal day (PD) 5. We found for the first time that
      this reaction was significantly suppressed by dexamethasone. The effect was
      specific to the novelty-induced component of behavior, while the intrinsic
      locomotor activity was not affected by glucocorticoid treatment. The suppression
      of the behavioral response to novelty was maximal at PD7 and vanquished at PD10
      11. In parallel with the hormonal effect on the behavior, dexamethasone
      upregulated the main cell death executor-active caspase-3 in the prefrontal
      cortex of 7-day old rats. Thus, dexamethasone-induced alterations in the novelty
      related behavior may be the earliest visible signs of the brain damage that could
      lead to forthcoming depressive state or schizophrenia, emerging as a result of
      neonatal stress or glucocorticoid treatment. 

PMID- 24886780
TI  - Advancing bag-of-visual-words representations for lesion classification in
      retinal images.
AB  - Diabetic Retinopathy (DR) is a complication of diabetes that can lead to
      blindness if not readily discovered. Automated screening algorithms have the
      potential to improve identification of patients who need further medical
      attention. However, the identification of lesions must be accurate to be useful
      for clinical application. The bag-of-visual-words (BoVW) algorithm employs a
      maximum-margin classifier in a flexible framework that is able to detect the most
      common DR-related lesions such as microaneurysms, cotton-wool spots and hard
      exudates. BoVW allows to bypass the need for pre- and post-processing of the
      retinographic images, as well as the need of specific ad hoc techniques for
      identification of each type of lesion. An extensive evaluation of the BoVW model,
      using three large retinograph datasets (DR1, DR2 and Messidor) with different
      resolution and collected by different healthcare personnel, was performed. The
      results demonstrate that the BoVW classification approach can identify different
      lesions within an image without having to utilize different algorithms for each
      lesion reducing processing time and providing a more flexible diagnostic system.
      Our BoVW scheme is based on sparse low-level feature detection with a Speeded-Up
      Robust Features (SURF) local descriptor, and mid-level features based on semi
      soft coding with max pooling. The best BoVW representation for retinal image
      classification was an area under the receiver operating characteristic curve (AUC
      ROC) of 97.8% (exudates) and 93.5% (red lesions), applying a cross-dataset
      validation protocol. To assess the accuracy for detecting cases that require
      referral within one year, the sparse extraction technique associated with semi
      soft coding and max pooling obtained an AUC of 94.2 +/- 2.0%, outperforming
      current methods. Those results indicate that, for retinal image classification
      tasks in clinical practice, BoVW is equal and, in some instances, surpasses
      results obtained using dense detection (widely believed to be the best choice in
      many vision problems) for the low-level descriptors.

PMID- 24886781
TI  - A short food-group-based dietary questionnaire is reliable and valid for
      assessing toddlers' dietary risk in relatively advantaged samples.
AB  - Identifying toddlers at dietary risk is crucial for determining who requires
      intervention to improve dietary patterns and reduce health consequences. The
      objectives of the present study were to develop a simple tool that assesses
      toddlers' dietary risk and investigate its reliability and validity. The nineteen
      item Toddler Dietary Questionnaire (TDQ) is informed by dietary patterns observed
      in Australian children aged 14 (n 552) and 24 (n 493) months and the Australian
      dietary guidelines. It assesses the intake of 'core' food groups (e.g. fruit,
      vegetables and dairy products) and 'non-core' food groups (e.g. high-fat, high
      sugar and/or high-salt foods and sweetened beverages) over the previous 7 d,
      which is then scored against a dietary risk criterion (0-100; higher score =
      higher risk). Parents of toddlers aged 12-36 months (Socio-Economic Index for
      Areas decile range 5-9) were asked to complete the TDQ for their child (n 111) on
      two occasions, 3.2 (SD 1.8) weeks apart, to assess test-retest reliability. They
      were also asked to complete a validated FFQ from which the risk score was
      calculated and compared with the TDQ-derived risk score (relative validity). Mean
      scores were highly correlated and not significantly different for reliability
      (intra-class correlation = 0.90, TDQ1 30.2 (SD 8.6) v. TDQ2 30.9 (SD 8.9); P=
      0.14) and validity (r 0.83, average TDQ ((TDQ1+TDQ2)/2) 30.5 (SD 8.4) v. FFQ 31.4
      (SD 8.1); P= 0.05). All the participants were classified into the same
      (reliability 75 %; validity 79 %) or adjacent (reliability 25 %; validity 21 %)
      risk category (low (0-24), moderate (25-49), high (50-74) and very high (75
      100)). Overall, the TDQ is a valid and reliable screening tool for identifying at
      risk toddlers in relatively advantaged samples.

PMID- 24886782
TI  - Identification of developmentally regulated PCP-responsive non-coding RNA, prt6,
      in the rat thalamus.
AB  - Schizophrenia and similar psychoses induced by NMDA-type glutamate receptor
      antagonists, such as phencyclidine (PCP) and ketamine, usually develop after
      adolescence. Moreover, adult-type behavioral disturbance following NMDA receptor
      antagonist application in rodents is observed after a critical period at around 3
      postnatal weeks. These observations suggest that the schizophrenic symptoms
      caused by and psychotomimetic effects of NMDA antagonists require the maturation
      of certain brain neuron circuits and molecular networks, which differentially
      respond to NMDA receptor antagonists across adolescence and the critical period.
      From this viewpoint, we have identified a novel developmentally regulated
      phencyclidine-responsive transcript from the rat thalamus, designated as prt6, as
      a candidate molecule involved in the above schizophrenia-related systems using a
      DNA microarray technique. The transcript is a non-coding RNA that includes
      sequences of at least two microRNAs, miR132 and miR212, and is expressed strongly
      in the brain and testis, with trace or non-detectable levels in the spleen,
      heart, liver, kidney, lung and skeletal muscle, as revealed by Northern blot
      analysis. The systemic administration of PCP (7.5 mg/kg, subcutaneously (s.c.))
      significantly elevated the expression of prt6 mRNA in the thalamus at postnatal
      days (PD) 32 and 50, but not at PD 8, 13, 20, or 24 as compared to saline-treated
      controls. At PD 50, another NMDA receptor antagonist, dizocilpine (0.5 mg/kg,
      s.c.), and a schizophrenomimetic dopamine agonist, methamphetamine (4.8 mg/kg,
      s.c.), mimicked a significant increase in the levels of thalamic prt6 mRNAs,
      while a D2 dopmamine receptor antagonist, haloperidol, partly inhibited the
      increasing influence of PCP on thalamic prt6 expression without its own effects.
      These data indicate that prt6 may be involved in the pathophysiology of the onset
      of drug-induced schizophrenia-like symptoms and schizophrenia through the
      possible dysregulation of target genes of the long non-coding RNA or microRNAs in
      the transcript. 

PMID- 24886783
TI  - Systematic pathway enrichment analysis of a genome-wide association study on
      breast cancer survival reveals an influence of genes involved in cell adhesion
      and calcium signaling on the patients' clinical outcome.
AB  - Genome-wide association studies (GWASs) may help to understand the effects of
      genetic polymorphisms on breast cancer (BC) progression and survival. However,
      they give only a focused view, which cannot capture the tremendous complexity of
      this disease. Therefore, we investigated data from a previously conducted GWAS on
      BC survival for enriched pathways by different enrichment analysis tools using
      the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of
      Genes and Genomes (KEGG). The goal was to identify the functional categories (GO
      terms and KEGG pathways) that are consistently overrepresented in a statistically
      significant way in the list of genes generated from the single nucleotide
      polymorphism (SNP) data. The SNPs with allelic p-value cut-offs 0.005 and 0.01
      were annotated to the genes by excluding or including a 20 kb up-and down-stream
      sequence of the genes and analyzed by six different tools. We identified eleven
      consistently enriched categories, the most significant ones relating to cell
      adhesion and calcium ion binding. Moreover, we investigated the similarity
      between our GWAS and the enrichment analyses of twelve published gene expression
      signatures for breast cancer prognosis. Five of them were commonly used and
      commercially available, five were based on different aspects of metastasis
      formation and two were developed from meta-analyses of published prognostic
      signatures. This comparison revealed similarities between our GWAS data and the
      general and the specific brain metastasis gene signatures as well as the Oncotype
      DX signature. As metastasis formation is a strong indicator of a patient's
      prognosis, this result reflects the survival aspect of the conducted GWAS and
      supports cell adhesion and calcium signaling as important pathways in cancer
      progression. 

PMID- 24886784
TI  - Digital gene-expression profiling analysis of the cholesterol-lowering effects of
      alfalfa saponin extract on laying hens.
AB  - BACKGROUND: To prevent cardiovascular disease, people are advised to limit their
      intake of dietary cholesterol to less than 300 mg/day. Egg consumption has been
      seriously reduced because of the high levels of cholesterol. The purpose of the
      present study was to evaluate the cholesterol-lowering effects of alfalfa saponin
      extract (ASE) in yolk and the molecular mechanisms underlying these effects using
      digital gene-expression profiling analysis. Liver and ovary tissues were isolated
      from laying hens fed with ASE for RNA sequencing. RESULTS: The cholesterol
      content of the yolks of eggs from hens fed 120 mg/kg ASE declined considerably on
      day 60. Other groups (60, 240, 480 mg/kg ASE group) also showed decreases, but
      they were not significant. Digital gene expression generated over nine million
      reads per sample, producing expression data for least 12,384 genes. Among these
      genes, 110 genes showed greater than normal expression in the liver and 107 genes
      showed greater than normal expression in the ovary. Cholesterol 7 alpha
      hydroxylase (Cyp7a1) and apolipoprotein H (Apoh), which act in the synthesis of
      bile acid and cholesterol efflux, showed more expression in the livers of hens
      given dietary ASE supplementation. In the ovary, levels of very low density
      lipoprotein receptor (Vldlr), apolipoprotein B (Apob), apovitellenin 1
      (ApovldlII) and vitellogenin (VtgI, VtgII and VtgIII) in ovary decreased with
      dietary ASE supplementation. CONCLUSION: Transcriptome analysis revealed that the
      molecular mechanisms underlying the cholesterol-lowering effects of ASE were
      partially mediated by enhancement of cholesterol efflux in the liver and this
      reduced of cholesterol deposition in the ovary.

PMID- 24886785
TI  - Transcriptome analysis of shade-induced inhibition on leaf size in relay
      intercropped soybean.
AB  - Multi-species intercropping is a sustainable agricultural practice worldwide used
      to utilize resources more efficiently. In intercropping systems, short crops
      often grow under vegetative shade of tall crops. Soybean, one important legume,
      is often planted in intercropping. However, little is known about the mechanisms
      of shade inhibition effect on leaf size in soybean leaves at the transcriptome
      level. We analyzed the transcriptome of shaded soybean leaves via RNA-Seq
      technology. We found that transcription 1085 genes in mature leaves and 1847
      genes in young leaves were significantly affected by shade. Gene ontology
      analyses showed that expression of genes enriched in polysaccharide metabolism
      was down-regulated, but genes enriched in auxin stimulus were up-regulated in
      mature leaves; and genes enriched in cell cycling, DNA-replication were down
      regulated in young leaves. These results suggest that the inhibition of higher
      auxin content and shortage of sugar supply on cell division and cell expansion
      contribute to smaller and thinner leaf morphology, which highlights potential
      research targets such as auxin and sugar regulation on leaves for crop adaptation
      to shade in intercropping. 

PMID- 24886786
TI  - Randomized clinical trial of the effects of screening and brief intervention for
      illicit drug use: the Life Shift/Shift Gears study.
AB  - BACKGROUND: Although screening, brief intervention, and referral to treatment
      (SBIRT) has shown promise for alcohol use, relatively little is known about its
      effectiveness for adult illicit drug use. This randomized controlled trial
      assessed the effectiveness of the SBIRT approach for outcomes related to drug use
      among patients visiting trauma and emergency departments (EDs) at two large,
      urban hospitals. METHODS: A total of 700 ED patients who admitted using illegal
      drugs in the past 30 days were recruited, consented, provided baseline measures
      of substance use and related problems measured with the Addiction Severity Index
      Lite (ASI-Lite), and then randomized to the Life Shift SBIRT intervention or to
      an attention-placebo control group focusing on driving and traffic safety (Shift
      Gears). Both groups received a level of motivational intervention matched to
      their condition and risk level by trained paraprofessional health educators.
      Separate measurement technicians conducted face-to-face follow-ups at 6 months
      post-intervention and collected hair samples to confirm reports of abstinence
      from drug use. The primary outcome measure of the study was past 30-day drug
      abstinence at 6 months post-intervention, as self-reported on the ASI-Lite.
      RESULTS: Of 700 participants, 292 (42%) completed follow-up. There were no
      significant differences in self-reported abstinence (12.5% vs. 12.0% , p = 0.88)
      for Life Shift and Shift Gears groups, respectively. When results of hair
      analyses were applied, the abstinence rate was 7 percent for Life Shift and 2
      percent for Shift Gears (p = .074). In an analysis in which results were imputed
      (n = 694), there was no significant difference in the ASI-Lite drug use composite
      scores (Life Shift +0.005 vs. Shift Gears +0.017, p = 0.12). CONCLUSIONS: In this
      randomized controlled trial, there was no evidence of effectiveness of SBIRT on
      the primary drug use outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT01683227.

PMID- 24886787
TI  - Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a
      randomized clinical trial.
AB  - IMPORTANCE: Most acute kidney injury observed in the hospital is defined by
      sudden mild or moderate increases in the serum creatinine concentration, which
      may persist for several days. Such acute kidney injury is associated with lower
      long-term kidney function. However, it has not been demonstrated that an
      intervention that reduces the risk of such acute kidney injury better preserves
      long-term kidney function. OBJECTIVES: To characterize the risk of acute kidney
      injury with an intervention in a randomized clinical trial and to determine if
      there is a difference between the 2 treatment groups in kidney function 1 year
      later. DESIGN, SETTING, AND PARTICIPANTS: The Coronary Artery Bypass Grafting
      Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients
      undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites
      in 19 countries. Patients were randomized to receive CABG surgery either with a
      beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From
      January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from
      CORONARY were enrolled into a kidney function substudy to record serum creatinine
      concentrations during the postoperative period and at 1 year. The last 1-year
      serum creatinine concentration was recorded on January 18, 2013. MAIN OUTCOMES
      AND MEASURES: Acute kidney injury within 30 days of surgery (>=50% increase in
      serum creatinine concentration from prerandomization concentration) and loss of
      kidney function at 1 year (>=20% loss in estimated glomerular filtration rate
      from prerandomization level). RESULTS: Off-pump (n = 1472) vs on-pump (n = 1460)
      CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%,
      respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there
      was no significant difference between the 2 groups in the loss of kidney function
      at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29],
      P = .23). Results were consistent with multiple alternate continuous and
      categorical definitions of acute kidney injury or kidney function loss, and in
      the subgroup with baseline chronic kidney disease. CONCLUSIONS AND RELEVANCE: Use
      of off-pump compared with on-pump CABG surgery reduced the risk of postoperative
      acute kidney injury, without evidence of better preserved kidney function with
      off-pump CABG surgery at 1 year. In this setting, an intervention that reduced
      the risk of mild to moderate acute kidney injury did not alter longer-term kidney
      function. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00463294.

PMID- 24886789
TI  - Impaired right inferior frontal gyrus response to contextual cues in male
      veterans with PTSD during response inhibition.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is often associated with
      impaired fear inhibition and decreased safety cue processing; however, studies
      capturing the cognitive aspect of inhibition and contextual cue processing are
      limited. In this fMRI study, the role of contextual cues in response inhibition
      was investigated. METHODS: Male medication-naive war veterans with PTSD, male
      control veterans (combat controls) and healthy nonmilitary men (healthy controls)
      underwent fMRI while performing the stop-signal anticipation task (SSAT). The
      SSAT evokes 2 forms of response inhibition: reactive inhibition (outright
      stopping) and proactive inhibition (anticipation of stopping based on contextual
      cues). RESULTS: We enrolled 28 veterans with PTSD, 26 combat controls and 25
      healthy controls in our study. Reduced reactive inhibition was observed in all
      veterans, both with and without PTSD, but not in nonmilitary controls, whereas
      decreased inhibition of the left pre/postcentral gyrus appeared to be
      specifically associated with PTSD. Impaired behavioural proactive inhibition was
      also specific to PTSD. Furthermore, the PTSD group showed a reduced right
      inferior frontal gyrus response during proactive inhibition compared with the
      combat control group. LIMITATIONS: Most patients with PTSD had comorbid
      psychiatric disorders, but such comorbidity is common in patients with PTSD.
      Also, the education level (estimate of intelligence) of participants, but not of
      their parents, differed among the groups. CONCLUSION: Our findings of reduced
      proactive inhibition imply that patients with PTSD show reduced contextual cue
      processing. These results complement previous findings on fear inhibition and
      demonstrate that contextual cue processing in patients with PTSD is also reduced
      during cognitive processes, indicating a more general deficit.

PMID- 24886788
TI  - Sustained anxiety increases amygdala-dorsomedial prefrontal coupling: a mechanism
      for maintaining an anxious state in healthy adults.
AB  - BACKGROUND: Neuroimaging research has traditionally explored fear and anxiety in
      response to discrete threat cues (e.g., during fear conditioning). However,
      anxiety is a sustained aversive state that can persist in the absence of discrete
      threats. Little is known about mechanisms that maintain anxiety states over a
      prolonged period. Here, we used a robust translational paradigm (threat of shock)
      to induce sustained anxiety. Recent translational work has implicated an amygdala
      prefrontal cortex (PFC) circuit in the maintenance of anxiety in rodents. To
      explore the functional homologues of this circuitry in humans, we used a novel
      paradigm to examine the impact of sustained anticipatory anxiety on amygdala-PFC
      intrinsic connectivity. METHODS: Task-independent fMRI data were collected in
      healthy participants during long-duration periods of shock anticipation and
      safety. We examined intrinsic functional connectivity. RESULTS: Our study
      involved 20 healthy participants. During sustained anxiety, amygdala activity was
      positively coupled with dorsomedial PFC (DMPFC) activity. High trait anxiety was
      associated with increased amygdala-DMPFC coupling. In addition, induced anxiety
      was associated with positive coupling between regions involved in defensive
      responding, and decreased coupling between regions involved in emotional control
      and the default mode network. LIMITATIONS: Inferences regarding anxious pathology
      should be made with caution because this study was conducted in healthy
      participants. CONCLUSION: Findings suggest that anticipatory anxiety increases
      intrinsic amygdala-DMPFC coupling and that the DMPFC may serve as a functional
      homologue for the rodent prefrontal regions by sustaining anxiety. Future
      research may use this defensive neural context to identify biomarkers of risk for
      anxious pathology and target these circuits for therapeutic intervention.

PMID- 24886791
TI  - Voltage-independent sodium channels emerge for an expression of activity-induced
      spontaneous spikes in GABAergic neurons.
AB  - BACKGROUND: Cerebral overexcitation needs inhibitory neurons be functionally
      upregulated to rebalance excitation vs. inhibition. For example, the intensive
      activities of GABAergic neurons induce spontaneous spikes, i.e., activity-induced
      spontaneous spikes (AISS). The mechanisms underlying AISS onset remain unclear.
      We investigated the roles of sodium channels in AISS induction and expression at
      hippocampal GABAergic neurons by electrophysiological approach. RESULTS: AISS
      expression includes additional spike capability above evoked spikes, and the full
      spikes in AISS comprise early phase (spikelets) and late phase, implying the
      emergence of new spikelet component. Compared with the late phase, the early
      phase is characterized as voltage-independent onset, less voltage-dependent
      upstroke and sensitivity to TTX. AISS expression and induction are independent of
      membrane potential changes. Therefore, AISS's spikelets express based on voltage
      independent sodium channels. In terms of AISS induction, the facilitation of
      voltage-gated sodium channel (VGSC) activation accelerates AISS onset, or vice
      versa. CONCLUSION: AISS expression in GABAergic neurons is triggered by the
      spikelets based on the functional emergence of voltage-independent sodium
      channels, which is driven by intensive VGSCs' activities.

PMID- 24886795
TI  - Pink-violaceous patches on the lower back, buttocks, and thighs of a 13-year-old
      girl.

PMID- 24886796
TI  - Understanding sexual violence perpetration.

PMID- 24886790
TI  - Immature dengue virus is infectious in human immature dendritic cells via
      interaction with the receptor molecule DC-SIGN.
AB  - BACKGROUND: Dengue Virus (DENV) is the most common mosquito-borne viral infection
      worldwide. Important target cells during DENV infection are macrophages,
      monocytes, and immature dendritic cells (imDCs). DENV-infected cells are known to
      secrete a large number of partially immature and fully immature particles
      alongside mature virions. Fully immature DENV particles are considered non
      infectious, but antibodies have been shown to rescue their infectious properties.
      This suggests that immature DENV particles only contribute to the viral load
      observed in patients with a heterologous DENV re-infection. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we re-evaluated the infectious properties of fully
      immature particles in absence and presence of anti-DENV human serum. We show that
      immature DENV is infectious in cells expressing DC-SIGN. Furthermore, we
      demonstrate that immature dendritic cells, in contrast to macrophage-like cells,
      do not support antibody-dependent enhancement of immature DENV.
      CONCLUSIONS/SIGNIFICANCE: Our data shows that immature DENV can infect imDCs
      through interaction with DC-SIGN, suggesting that immature and partially immature
      DENV particles may contribute to dengue pathogenesis during primary infection.
      Furthermore, since antibodies do not further stimulate DENV infectivity on imDCs
      we propose that macrophages/monocytes rather than imDCs contribute to the
      increased viral load observed during severe heterotypic DENV re-infections.

PMID- 24886797
TI  - Understanding sexual violence perpetration.

PMID- 24886798
TI  - Understanding sexual violence perpetration-reply.

PMID- 24886799
TI  - Survival at a gestational age of 24 weeks in the Netherlands.

PMID- 24886800
TI  - Survival at a gestational age of 24 weeks in the Netherlands--reply.

PMID- 24886801
TI  - Too few medicines for children with cancer.

PMID- 24886803
TI  - Home visiting narrative: rewrite is in progress.

PMID- 24886802
TI  - Too few medicines for children with cancer--reply.

PMID- 24886804
TI  - Are high prices a barrier to human papillomavirus vaccination in the United
      States? Not in Italy.

PMID- 24886805
TI  - Teen driving.

PMID- 24886806
TI  - Effects of 940 MHz EMF on bioluminescence and oxidative response of stable
      luciferase producing HEK cells.
AB  - The effects of mobile phone frequency electromagnetic field (RF-EMF, 940 MHz) on
      a stable cell line (HEK293T) harbouring the firefly luciferase gene were
      evaluated. A waveguide exposure system with 1 W input power provided the mean
      specific absorption rate of ~0.09 W kg(-1) in 35 mm Petri dishes. The effects of
      exposure duration (15, 30, 45, 60 and 90 min) on luciferase activity and
      oxidative response elements were investigated. Endogenous luciferase activity was
      reduced after 30 and 45 min of continuous exposure, while after 60 min, the
      exposed cell lysate showed higher luciferase activity compared with the non
      exposed control. Reactive oxygen species (ROS) generation was highest in the 30
      min exposed cells as studied by 2',7'-dichlorodihydrofluorescein diacetate (DCFH
      DA) fluorescence. The observed boost in ROS was then followed by a sharp rise in
      catalase (CAT) and superoxide dismutase (SOD) activity and elevation of
      glutathione (GSH) during the 45 min exposure. Decrease in lipid peroxidation
      (malondialdehyde, MDA) was meaningful for the 45 and 60 min exposed cells.
      Therefore, it appears that an increase in the activity of luciferase after 60 min
      of continuous exposure could be associated with a decrease in ROS level caused by
      activation of the oxidative response. This ability in cells to overcome oxidative
      stress and compensate the luciferase activity could also be responsible for the
      adaptive response mechanism detected in ionizing radiation studies with RF-EMF
      pre-treatments. 

PMID- 24886808
TI  - A white phosphorescent coordination polymer with Cu2I2 alternating units linked
      by benzo-18-crown-6.
AB  - A new approach has been illustrated for the development of stable, efficient, and
      environmentally "friendly" white phosphorescent materials. Under mild conditions,
      a new one-dimensional coordination polymer has been prepared from benzo-18-crown
      6 with CuI in the presence of KI, which is capable of emitting direct white light
      in the solid state. 

PMID- 24886807
TI  - Liver X receptors alpha gene (NR1H3) promoter polymorphisms are associated with
      systemic lupus erythematosus in Koreans.
AB  - INTRODUCTION: Liver X receptors are established sensors of lipid and cholesterol
      homeostasis. Recent studies have reported that these receptors are involved in
      the regulation of inflammation and immune responses. We attempted to identify
      single nucleotide polymorphisms (SNPs) of the NR1H3 gene associated with the
      susceptibility to systemic lupus erythematosus (SLE). METHODS: SNPs were
      genotyped using SNaPSHOT assay in 300 Korean patients with SLE and 217 normal
      controls (NC), and in replication samples (160 SLE patients and 143 NC). Also,
      the functional effects of NR1H3 gene promoter polymorphisms were analyzed using a
      luciferase assay, real-time polymerase chain reaction, B cell proliferation assay
      and an electrophoretic mobility shift assay. RESULTS: We identified five
      polymorphisms: -1851 T > C (rs3758673), -1830 T > C (rs3758674), -1003 G > A
      (new), -840 C > A (rs61896015) and -115 G > A (rs12221497). There was a
      significant and reproducible difference in the -1830 T > C, -1003 G > A and -115
      G > A polymorphisms between the SLE and the NC. Luciferase activity of the
      structure containing -1830 C was less enhanced compared to the structure
      containing -1830 T in basal, GW3965 and T0901317 treated Hep3B cells (P = 0.009,
      P = 0.034 and P <0.001, respectively). Proliferation of the -1830 TC type was
      increased compared to the -1830 TT type in basal, GW3965 and T0901317 treated B
      cells from SLE patients (P = 0.011, P = 0.040 and P = 0.017, respectively).
      Transcription factor GATA-3 preferentially bound the -1830 T allele in the
      promoter. CONCLUSIONS: NR1H3 genetic polymorphisms may be associated with disease
      susceptibility and clinical manifestations of SLE. Specifically, -1830 T > C
      polymorphism within NR1H3 promoter region may be involved in regulation of NR1H3
      expression.

PMID- 24886809
TI  - Differential proteomic analysis of the pancreas of diabetic db/db mice reveals
      the proteins involved in the development of complications of diabetes mellitus.
AB  - Type 2 diabetes mellitus is characterized by hyperglycemia and insulin
      resistance. Diabetes results from pancreatic inability to secrete the insulin
      needed to overcome this resistance. We analyzed the protein profile from the
      pancreas of ten-week old diabetic db/db and wild type mice through proteomics.
      Pancreatic proteins were separated in two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and significant changes in db/db mice respect to wild
      type mice were observed in 27 proteins. Twenty five proteins were identified by
      matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) and
      their interactions were analyzed using search tool for the retrieval of
      interacting genes/proteins (STRING) and database for annotation, visualization
      and integrated discovery (DAVID). Some of these proteins were Pancreatic alpha
      amylase, Cytochrome b5, Lithostathine-1, Lithostathine-2, Chymotrypsinogen B,
      Peroxiredoxin-4, Aspartyl aminopeptidase, Endoplasmin, and others, which are
      involved in the metabolism of carbohydrates and proteins, as well as in oxidative
      stress, and inflammation. Remarkably, these are mostly endoplasmic reticulum
      proteins related to peptidase activity, i.e., they are involved in proteolysis,
      glucose catabolism and in the tumor necrosis factor-mediated signaling pathway.
      These results suggest mechanisms for insulin resistance, and the chronic
      inflammatory state observed in diabetes. 

PMID- 24886811
TI  - A cautionary note on the use of split-YFP/BiFC in plant protein-protein
      interaction studies.
AB  - Since its introduction in plants 10 years ago, the bimolecular fluorescence
      complementation (BiFC) method, or split-YFP (yellow fluorescent protein), has
      gained popularity within the plant biology field as a method to study protein
      protein interactions. BiFC is based on the restoration of fluorescence after the
      two non-fluorescent halves of a fluorescent protein are brought together by a
      protein-protein interaction event. The major drawback of BiFC is that the
      fluorescent protein halves are prone to self-assembly independent of a protein
      protein interaction event. To circumvent this problem, several modifications of
      the technique have been suggested, but these modifications have not lead to
      improvements in plant BiFC protocols. Therefore, it remains crucial to include
      appropriate internal controls. Our literature survey of recent BiFC studies in
      plants shows that most studies use inappropriate controls, and a qualitative
      rather than quantitative read-out of fluorescence. Therefore, we provide a
      cautionary note and beginner's guideline for the setup of BiFC experiments,
      discussing each step of the protocol, including vector choice, plant expression
      systems, negative controls, and signal detection. In addition, we present our
      experience with BiFC with respect to self-assembly, peptide linkers, and
      incubation temperature. With this note, we aim to provide a guideline that will
      improve the quality of plant BiFC experiments. 

PMID- 24886812
TI  - Flowering as the most highly sensitive period of grapevine (Vitis vinifera L. cv
      Mourvedre) to the Botryosphaeria dieback agents Neofusicoccum parvum and Diplodia
      seriata infection.
AB  - Botryosphaeria dieback is a fungal grapevine trunk disease that currently
      represents a threat for viticulture worldwide because of the important economical
      losses due to reduced yield of affected plants and their premature death.
      Neofusicoccum parvum and Diplodia seriata are among the causal agents. Vine green
      stems were artificially infected with N. parvum or D. seriata at the onset of
      three different phenological stages (G stage (separated clusters), flowering and
      veraison). Highest mean lesion lengths were recorded at flowering. Major proteome
      changes associated to artificial infections during the three different
      phenological stages were also reported using two dimensional gel electrophoresis
      (2D)-based analysis. Twenty (G stage), 15 (flowering) and 13 (veraison)
      differentially expressed protein spots were subjected to nanoLC-MS/MS and a total
      of 247, 54 and 25 proteins were respectively identified. At flowering, a weaker
      response to the infection was likely activated as compared to the other stages,
      and some defense-related proteins were even down regulated (e.g., superoxide
      dismutase, major latex-like protein, and pathogenesis related protein 10).
      Globally, the flowering period seemed to represent the period of highest
      sensitivity of grapevine to Botryosphaeria dieback agent infection, possibly
      being related to the high metabolic activity in the inflorescences. 

PMID- 24886816
TI  - Gamma knife treatment of brainstem metastases.
AB  - The management of brainstem metastases is challenging. Surgical treatment is
      usually not an option, and chemotherapy is of limited utility. Stereotactic
      radiosurgery has emerged as a promising palliative treatment modality in these
      cases. The goal of this study is to assess our single institution experience
      treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This
      retrospective chart review studied 41 patients with brainstem metastases treated
      with GKRS. The most common primary tumors were lung, breast, renal cell
      carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen
      (46%) of the patients received whole brain radiation therapy (WBRT) prior to or
      concurrent with GKRS treatment. Thirty (73%) of the patients had a single
      brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival
      at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local
      tumor control was achieved in 91% of patients, and there was one patient who had
      a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80
      and the absence of prior WBRT were predictors for improved survival on
      multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively).
      GKRS was an effective treatment for brainstem metastases, with excellent local
      tumor control. 

PMID- 24886815
TI  - Genotypic characterization of Escherichia coli O157:H7 isolates from different
      sources in the North-West Province, South Africa, using enterobacterial
      repetitive intergenic consensus PCR analysis.
AB  - In many developing countries, proper hygiene is not strictly implemented when
      animals are slaughtered and meat products become contaminated. Contaminated meat
      may contain Escherichia coli (E. coli) O157:H7 that could cause diseases in
      humans if these food products are consumed undercooked. In the present study, a
      total of 94 confirmed E. coli O157:H7 isolates were subjected to the
      enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction
      (PCR) typing to generate genetic fingerprints. The ERIC fragments were resolved
      by electrophoresis on 2% (w/v) agarose gels. The presence, absence and intensity
      of band data were obtained, exported to Microsoft Excel (Microsoft Office 2003)
      and used to generate a data matrix. The unweighted pair group method with
      arithmetic mean (UPGMA) and complete linkage algorithms were used to analyze the
      percentage of similarity and matrix data. Relationships between the various
      profiles and/or lanes were expressed as dendrograms. Data from groups of related
      lanes were compiled and reported on cluster tables. ERIC fragments ranged from
      one to 15 per isolate, and their sizes varied from 0.25 to 0.771 kb. A large
      proportion of the isolates produced an ERIC banding pattern with three duplets
      ranging in sizes from 0.408 to 0.628 kb. Eight major clusters (I-VIII) were
      identified. Overall, the remarkable similarities (72% to 91%) between the ERIC
      profiles for the isolate from animal species and their corresponding food
      products indicated some form of contamination, which may not exclude those at the
      level of the abattoirs. These results reveal that ERIC PCR analysis can be
      reliable in comparing the genetic profiles of E. coli O157:H7 from different
      sources in the North-West Province of South Africa. 

PMID- 24886810
TI  - NOD-like receptors in intestinal homeostasis and epithelial tissue repair.
AB  - The intestinal epithelium constitutes a dynamic physical barrier segregating the
      luminal content from the underlying mucosal tissue. Following injury, the
      epithelial integrity is restored by rapid migration of intestinal epithelial
      cells (IECs) across the denuded area in a process known as wound healing. Hence,
      through a sequence of events involving restitution, proliferation and
      differentiation of IECs the gap is resealed and homeostasis reestablished.
      Relapsing damage followed by healing of the inflamed mucosa is a hallmark of
      several intestinal disorders including inflammatory bowel diseases (IBD). While
      several regulatory peptides, growth factors and cytokines stimulate restitution
      of the epithelial layer after injury, recent evidence in the field underscores
      the contribution of innate immunity in controlling this process. In particular,
      nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical
      roles in sensing the commensal microbiota, maintaining homeostasis, and
      regulating intestinal inflammation. Here, we review the process of intestinal
      epithelial tissue repair and we specifically focus on the impact of NLR-mediated
      signaling mechanisms involved in governing epithelial wound healing during
      disease. 

PMID- 24886814
TI  - Clinical impact of tumor-infiltrating inflammatory cells in primary small cell
      esophageal carcinoma.
AB  - Primary small cell esophageal carcinoma is a rare and aggressive type of
      gastrointestinal cancer with poor prognosis. In the present study, the impact of
      tumour infiltrating inflammatory cells on clinico-pathological characteristics
      and the patients' prognosis were analysed. A total of 36 small cell esophageal
      carcinomas, 19 adjacent normal tissues and 16 esophageal squamous cell carcinoma
      samples were collected. Qualified pathologists examined eosinophils, neutrophils,
      lymphocytes and macrophages on histochemical slides. The infiltration of
      eosinophils and macrophages in small cell esophageal carcinoma was significantly
      increased as compared with tumor adjacent normal tissues, and was significantly
      less in esophageal squamous cell carcinoma. Macrophage count was significantly
      associated with (p = 0.015) lymph node-stage in small cell esophageal carcinoma.
      When we grouped patients into two groups by counts of infiltrated inflammatory
      cells, Kaplan-Meier analysis revealed that high macrophage infiltration group (p
      = 0.004) and high eosinophil infiltration group (p = 0.027) had significantly
      enhanced survival. In addition, multivariate analysis unveiled that eosinophil
      count (p = 0.002) and chemotherapy (Yes vs. No, p = 0.001) were independent
      prognostic indicators. Taken together, infiltration of macrophages and
      eosinophils into the solid tumor appear to be important in the progression of
      small cell esophageal carcinoma and patients' prognosis. 

PMID- 24886813
TI  - Computational and experimental approaches to reveal the effects of single
      nucleotide polymorphisms with respect to disease diagnostics.
AB  - DNA mutations are the cause of many human diseases and they are the reason for
      natural differences among individuals by affecting the structure, function,
      interactions, and other properties of DNA and expressed proteins. The ability to
      predict whether a given mutation is disease-causing or harmless is of great
      importance for the early detection of patients with a high risk of developing a
      particular disease and would pave the way for personalized medicine and
      diagnostics. Here we review existing methods and techniques to study and predict
      the effects of DNA mutations from three different perspectives: in silico, in
      vitro and in vivo. It is emphasized that the problem is complicated and
      successful detection of a pathogenic mutation frequently requires a combination
      of several methods and a knowledge of the biological phenomena associated with
      the corresponding macromolecules. 

PMID- 24886817
TI  - Corilagin attenuates aerosol bleomycin-induced experimental lung injury.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few
      clinically effective therapies. Corilagin is a tannin derivative which shows anti
      inflammatory and antifibrotics properties and is potentiated in treating IPF.
      Here, we investigated the effect of corilagin on lung injury following bleomycin
      exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin
      induced lung fibrosis as assessed by H&E; Masson's trichrome staining and lung
      hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic
      lung cells and prevented lung epithelial cells from membrane breakdown, effluence
      of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure
      induced expression of MDA, IKKalpha, phosphorylated IKKalpha (p-IKKalpha), NF
      kappaB P65, TNF-alpha and IL-1beta, and reduced I-kappaB expression in mice lung
      tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg
      i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits
      TGF-beta1 production and alpha-SMA expression in lung tissue samples. Taken
      together, these findings confirmed that corilagin attenuates bleomycin-induced
      epithelial injury and fibrosis via inactivation of oxidative stress,
      proinflammatory cytokine release and NF-kappaB and TGF-beta1 signaling. Corilagin
      may serve as a promising therapeutic agent for pulmonary fibrosis. 

PMID- 24886818
TI  - Multiplex hydrolysis probe real-time PCR for simultaneous detection of hepatitis
      A virus and hepatitis E virus.
AB  - Detection of hepatitis viral infections has traditionally relied on the
      circulating antibody test using the enzyme-linked immunosorbent assay. However,
      multiplex real-time PCR has been increasingly used for a variety of viral nucleic
      acid detections and has proven to be superior to traditional methods. Hepatitis A
      virus (HAV) and hepatitis E virus (HEV) are the major causes of acute hepatitis
      worldwide; both HAV and HEV infection are a main public health problem. In the
      present study, a one-step multiplex reverse transcriptase quantitative polymerase
      chain reaction assay using hydrolysis probes was developed for simultaneously
      detecting HAV and HEV. This novel detection system proved specific to the target
      viruses, to be highly sensitive and to be applicable to clinical sera samples,
      making it useful for rapid, accurate and feasible identification of HAV and HEV. 

PMID- 24886821
TI  - Arterial stiffness and hypertension in a large population of untreated
      individuals: the Rotterdam Study.
AB  - OBJECTIVE: We studied whether arterial stiffness measured as aortic pulse wave
      velocity (aPWV) and carotid distensibility was associated with different subtypes
      of hypertension in a large population of untreated middle-aged and elderly men
      and women. METHODS: The study was conducted within the framework of the
      population-based Rotterdam Study. We included 4088 individuals with information
      on aPWV, with 3554 individuals with carotid distensibility measurements without
      use of antihypertensive medication. Isolated systolic hypertension (ISH) was
      defined as SBP at least 140 mmHg and DBP less than 90 mmHg. Combined systolic and
      diastolic hypertension (Sys/Dia hypertension) was defined as SBP at least 140
      mmHg and DBP at least 90 mmHg. Analysis of covariance was used to compare means
      of arterial stiffness for the different subtypes of hypertension. Multinomial
      logistic regression analysis was performed to investigate the association of
      arterial stiffness and the subtypes of hypertension in models adjusted for age,
      sex, mean arterial pressure, heart rate and cardiovascular risk factors. RESULTS:
      The mean age of the individuals was 68 years: 45.3% were men, 1597 individuals
      had ISH and 441 individuals had Sys/Dia hypertension. aPWV was higher (13.2 vs.
      12.9 m/s; P = 0.008) in individuals with ISH compared to those with Sys/Dia
      hypertension. Multivariate odds ratios and corresponding 95% confidence interval
      of aPWV for ISH were 1.53 (1.38-1.71) and 1.28 (1.09-1.53) for Sys/Dia
      hypertension. Corresponding odds ratios associated with carotid distensibility
      were 0.84 (0.75-0.94) and 0.66 (0.54-0.81), respectively. Age significantly
      modified the association of aPWV with subtypes of hypertension (P < 0.001).
      CONCLUSION: In a large untreated population, we found significant associations of
      both aPWV and carotid distensibility with ISH and Sys/Dia hypertension.
      individuals with ISH had higher values of aortic stiffness when compared to
      individuals with Sys/Dia hypertension, a difference that was most pronounced at
      older age. The results suggest that aortic stiffness contributes to ISH in older
      individuals without treatment for hypertension.

PMID- 24886822
TI  - Chymase inhibition improves vascular dysfunction and survival in stroke-prone
      spontaneously hypertensive rats.
AB  - OBJECTIVE: To clarify the role of chymase in hypertension, we evaluated the
      effect of a chymase inhibitor, TY-51469, on vascular dysfunction and survival in
      stroke-prone spontaneously hypertensive rats (SHR-SP). METHODS: SHR-SP were
      treated with TY-51469 (1 mg/kg per day) or placebo from 4 to 12 weeks old or
      until death. Wistar-Kyoto rats were used as a normal group. RESULTS: SBP was
      significantly higher in both the placebo and TY-51469 groups than in the normal
      group, but there was no significant difference between the two treatment groups.
      Plasma renin, angiotensin-converting enzyme activity and angiotensin II levels
      were not different between the placebo and TY-51469 groups. In contrast, vascular
      chymase-like activity was significantly higher in the placebo than in the normal
      group, but it was reduced by TY-51469. Acetylcholine-induced vascular relaxation
      was significantly higher in the TY-51469 group than in the placebo group. There
      was significant augmentation of the number of monocytes/macrophages and matrix
      metalloproteinase-9 activity in aortic tissue from the placebo group compared
      with the normal group, and these changes were attenuated by TY-51469. There were
      also significant increases in mRNA levels of monocyte chemoattractant protein-1
      and tumor necrosis factor-alpha in the placebo group that were attenuated by TY
      51469. Cumulative survival was significantly prolonged in the TY-51469 group
      compared with the placebo group. CONCLUSION: Chymase might play an important role
      in vascular dysfunction via augmentation both of matrix metalloproteinase-9
      activity and monocyte/macrophage accumulation in SHR-SP, and its inhibition may
      be useful for preventing vascular remodeling and prolonging survival.

PMID- 24886820
TI  - Is boosting the immune system in sepsis appropriate?
AB  - A relative immunosuppression is observed in patients after sepsis, trauma, burns,
      or any severe insults. It is currently proposed that selected patients will
      benefit from treatment aimed at boosting their immune systems. However, the host
      immune response needs to be considered in context with pathogen-type, timing,and
      mainly tissue specificity. Indeed, the immune status of leukocytes is not
      universally decreased and their activated status in tissues contributes to organ
      failure. Accordingly, any new immune-stimulatory therapeutic intervention should
      take into consideration potentially deleterious effects in some situations.

PMID- 24886823
TI  - European Society of Hypertension practice guidelines for ambulatory blood
      pressure monitoring.
AB  - Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both
      clinical practice and hypertension research, a group of scientists, participating
      in the European Society of Hypertension Working Group on blood pressure
      monitoring and cardiovascular variability, in year 2013 published a comprehensive
      position paper dealing with all aspects of the technique, based on the available
      scientific evidence for ABPM. The present work represents an updated schematic
      summary of the most important aspects related to the use of ABPM in daily
      practice, and is aimed at providing recommendations for proper use of this
      technique in a clinical setting by both specialists and practicing physicians.
      The present article details the requirements and the methodological issues to be
      addressed for using ABPM in clinical practice, The clinical indications for ABPM
      suggested by the available studies, among which white-coat phenomena, masked
      hypertension, and nocturnal hypertension, are outlined in detail, and the place
      of home measurement of blood pressure in relation to ABPM is discussed. The role
      of ABPM in pharmacological, epidemiological, and clinical research is also
      briefly mentioned. Finally, the implementation of ABPM in practice is considered
      in relation to the situation of different countries with regard to the
      reimbursement and the availability of ABPM in primary care practices, hospital
      clinics, and pharmacies. 

PMID- 24886824
TI  - How do viruses trick B cells into becoming lymphomas?
AB  - PURPOSE OF REVIEW: Since the discovery of Epstein-Barr virus in Burkitt's
      lymphoma 50  years ago, only one other virus, namely Kaposi's sarcoma-associated
      herpesvirus/human herpesvirus-8, has been confirmed to be a direct cause of B
      cell lymphoma. Here we will review the evidence for Epstein-Barr virus and
      Kaposi's sarcoma-associated herpesvirus as causal lymphoma agents. RECENT
      FINDINGS: A deeper understanding of specific mechanisms by which Epstein-Barr
      virus and Kaposi's sarcoma-associated herpesvirus cause B-cell lymphomas has been
      acquired over the past years, in particular with respect to viral protein
      interactions with host cell pathways, and microRNA functions. Specific therapies
      based on knowledge of viral functions are beginning to be evaluated, mostly in
      preclinical models. SUMMARY: Understanding the causal associations of specific
      infectious agents with certain B-cell lymphomas has allowed more accurate
      diagnosis and classification. A deeper knowledge of the specific mechanisms of
      transformation is essential to begin assessing whether virus-targeted treatment
      modalities may be used in the future.

PMID- 24886825
TI  - Chemical reactivation of quenched fluorescent protein molecules enables resin
      embedded fluorescence microimaging.
AB  - Resin embedding is a well-established technique to prepare biological specimens
      for microscopic imaging. However, it is not compatible with modern green
      fluorescent protein (GFP) fluorescent-labelling technique because it
      significantly quenches the fluorescence of GFP and its variants. Previous
      empirical optimization efforts are good for thin tissue but not successful on
      macroscopic tissue blocks as the quenching mechanism remains uncertain. Here we
      show most of the quenched GFP molecules are structurally preserved and not
      denatured after routine embedding in resin, and can be chemically reactivated to
      a fluorescent state by alkaline buffer during imaging. We observe up to 98%
      preservation in yellow-fluorescent protein case, and improve the fluorescence
      intensity 11.8-fold compared with unprocessed samples. We demonstrate
      fluorescence microimaging of resin-embedded EGFP/EYFP-labelled tissue block
      without noticeable loss of labelled structures. This work provides a turning
      point for the imaging of fluorescent protein-labelled specimens after resin
      embedding. 

PMID- 24886826
TI  - beta-lactam antibiotic concentrations during continuous renal replacement
      therapy.
AB  - INTRODUCTION: The use of standard doses of beta-lactam antibiotics during
      continuous renal replacement therapy (CRRT) may result in inadequate serum
      concentrations. The aim of this study was to evaluate the adequacy of unadjusted
      drug regimens (i.e., similar to those used in patients with normal renal
      function) in patients treated with CRRT and the influence of CRRT intensity on
      drug clearance. METHODS: We reviewed data from 50 consecutive adult patients
      admitted to our Department of Intensive Care in whom routine therapeutic drug
      monitoring (TDM) of broad-spectrum beta-lactam antibiotics (ceftazidime or
      cefepime, CEF; piperacillin/tazobactam; TZP; meropenem, MEM) was performed using
      unadjusted beta-lactam antibiotics regimens (CEF = 2 g q8h; TZP = 4 g q6h; MEM =
      1 g q8h). Serum drug concentrations were measured twice during the elimination
      phase by high-performance liquid chromatography (HPLC-UV). We considered therapy
      was adequate when serum drug concentrations were between 4 and 8 times the
      minimal inhibitory concentration (MIC) of Pseudomonas aeruginosa during optimal
      periods of time for each drug (>=70% for CEF; >= 50% for TZP; >= 40% for MEM).
      Therapy was considered as early (ET) or late (LT) phase if TDM was performed
      within 48 hours of antibiotic initiation or later on, respectively. RESULTS: We
      collected 73 serum samples from 50 patients (age 58 +/- 13 years; Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score on admission 21 (17
      25)), 35 during ET and 38 during LT. Drug concentrations were above 4 times the
      MIC in 63 (90%), but above 8 times the MIC in 39 (53%) samples. The proportions
      of patients with adequate drug concentrations during ET and LT were quite
      similar. We found a weak but significant correlation between beta-lactam
      antibiotics clearance and CRRT intensity. CONCLUSIONS: In septic patients
      undergoing CRRT, doses of beta-lactam antibiotics similar to those given to
      patients with normal renal function achieved drug levels above the target
      threshold in 90% of samples. Nevertheless, 53% of samples were associated with
      very high drug levels and daily drug regimens may need to be adapted accordingly.

PMID- 24886827
TI  - Differential regulation of Gli proteins by Sufu in the lung affects PDGF
      signaling and myofibroblast development.
AB  - Mammalian Hedgehog (Hh) signaling relies on three Gli transcription factors to
      mediate Hh responses. This process is controlled in part by a major negative
      regulator, Sufu, through its effects on Gli protein level, distribution and
      activity. In this report, we showed that Sufu regulates Gli1 protein levels by
      antagonizing Numb/Itch. Otherwise, Numb/Itch would induce Gli1 protein
      degradation. This is in contrast to inhibition of Spop-mediated degradation of
      Gli2/3 by Sufu. Thus, controlling protein levels of all three Gli genes by Sufu
      is a conserved mechanism to modulate Hh responses albeit via distinct pathways.
      These findings in cell-based assays were further validated in vivo. In analyzing
      how Sufu controls Gli proteins in different tissues, we discovered that loss of
      Sufu in the lung exerts different effects on Hh target genes. Hh targets
      Ptch1/Hhip are upregulated in Sufu-deficient lungs, consistent with Hh pathway
      activation. Surprisingly, protein levels of Hh target Gli1 are reduced. We also
      found that myofibroblasts are absent from many prospective alveoli of Sufu
      deficient lungs. Myofibroblast development is dependent on PDGF signaling.
      Interestingly, analysis of the Pdgfra promoter revealed a canonical Gli-binding
      site where Gli1 resides. These studies support a model in which loss of Sufu
      contributes to compromised Pdgfra activation and disrupts myofibroblast
      development in the lung. Our work illustrates the unappreciated complexity of Hh
      responses where distinct Hh targets could respond differently depending on the
      availability of Gli proteins that control their expression. 

PMID- 24886828
TI  - Emergence of tissue sensitivity to Hox protein levels underlies the evolution of
      an adaptive morphological trait.
AB  - Growth control scales morphological attributes and, therefore, provides a
      critical contribution to the evolution of adaptive traits. Yet, the genetic
      mechanisms underlying growth in the context of specific ecological adaptations
      are poorly understood. In water striders, adaptation to locomotion on the water
      surface is associated with allometric and functional changes in thoracic
      appendages, such that T2-legs, used as propelling oars, are longer than T3-legs,
      used as steering rudders. The Hox gene Ubx establishes this derived morphology by
      elongating T2-legs but shortening T3-legs. Using gene expression assays, RNAi
      knockdown, and comparative transcriptomics, we demonstrate that the evolution of
      water surface rowing as a novel means of locomotion is associated with the
      evolution of a dose-dependent promoting-repressing effect of Ubx on leg growth.
      In the water strider Limnoporus dissortis, T3-legs express six to seven times
      higher levels of Ubx compared to T2-legs. Ubx RNAi shortens T2-legs and the
      severity of this phenotype increases with increased depletion of Ubx protein.
      Conversely, Ubx RNAi lengthens T3-legs but this phenotype is partially rescued
      when Ubx protein is further depleted. This dose-dependent effect of Ubx on leg
      growth is absent in non-rowing relatives that retain the ancestral relative leg
      length. We also show that the spatial patterns of expression of dpp, wg, hh,
      egfr, dll, exd, hth, and dac are unchanged in Ubx RNAi treatments. This indicates
      that the dose-dependent opposite effect of Ubx on T2- and T3-legs operates
      without any apparent effect on the spatial expression of major leg patterning
      genes. Our data suggest that scaling of adaptive allometries can evolve through
      changes in the levels of expression of Hox proteins early during ontogeny, and in
      the sensitivity of the tissues that express them, without any major effects on
      pattern formation. 

PMID- 24886831
TI  - [Fatal poisoning in Mali].
AB  - AIMS: The aim of this study was to determine the epidemiological characteristics
      of the cases of fatal poisoning in Mali. METHODS: This retrospective study
      examined the cases of fatal poisoning recorded between 2000 and 2010 in six
      Health Reference centers, six regional hospitals and three university hospitals
      in the district of Bamako. RESULTS: During the study period, 146 cases of fatal
      poisoning were recorded, accounting for 4.6% of all poisoning cases during this
      period. The average age of patients who died was 24 +/- 17.7 years with a female
      male ratio of 1.05. Nearly half (43%) were younger than 20 years. The ingestion
      was intentional in 66.4% of cases, mainly suicide attempts (47%) and therapeutic
      errors (19%). The median time until arrival at hospital was 8 hours after
      poisoning with multiple and varied clinical signs. CONCLUSIONS: Decreasing the
      mortality rate from poison ingestion requires increasing public awareness about
      poisons and improving emergency service equipment and health personnel training.

PMID- 24886832
TI  - Rapid determination of hydrogen peroxide produced by Lactobacillus using enzyme
      coupled rhodamine isocyanide/calcium phosphate nanoparticles.
AB  - A sensitive method for detecting hydrogen peroxide (H2O2) using rhodamine
      isocyanide incorporated calcium phosphate nanoparticles (Rho/CaP) was developed.
      The synthesized nanoparticles were characterized based on transmission electron
      microscopy (TEM), scanning electron microscopy (SEM), Fourier transformed
      infrared spectroscopy (FTIR), Raman spectroscopy, energy-dispersive X-ray
      spectroscopy (EDX) and X-ray diffraction patterns (XRD). To study the
      application, the nanoparticles were functionalized with horse radish peroxidase
      (HRP) based on aminopropyl triethoxy silane (APTES) and used as tools to detect
      H2O2. The detection strategy was based on fluorescence quenching or colorimetric
      detection. The enzyme immobilized nanoparticles were titrated with different
      concentrations of H2O2 and a fixed concentration of O-phenylenediamine (OPD). The
      HRP conjugated Rho/CaP strongly catalyzed H2O2 oxidation of OPD that caused
      fluorescence quenching at 575 nm. For colorimetric detection, the OPD product was
      read at 492 nm. In the fluorescence quenching assay, the minimum detectable
      concentration was ~1 pmol in contrast to ~5 nmol in the colorimetric assay. The
      minimum detectable concentration by visual detection was ~500 nmol. The
      specificity of the developed assay method was examined with different
      interferences which did not produce any significant response. This assay was
      applied, along with a commercially available kit to compare the H2O2 production
      capacities of different Lactobacillus strains. The results indicated that the
      developed assay and commercially available kit methods were highly correlated.
      The fluorescence quenching kinetics is also discussed.

PMID- 24886830
TI  - Identification of nuclear-enriched miRNAs during mouse granulopoiesis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are coordinators of cellular differentiation,
      including granulopoiesis. Although differential expression of many miRNAs is
      associated with the maturation of granulocytes, analysis of differentially
      expressed miRNAs and their cellular localization across all stages of
      granulopoiesis, starting from hemopoietic stems cells, is not well characterized.
      METHODS: We analyzed whole cell miRNA and mRNA expression during granulopoiesis
      using Taqman low-density and Affymetrix arrays respectively. We also performed
      nuclear and cytoplasmic fractionation followed by Taqman low-density array and/or
      quantitative PCR to identify nuclear-enriched miRNAs in hemopoietic
      stem/progenitor cells, promyelocytes, myelocytes, granulocytes and several
      hemopoietic cell lines. Anti-correlation between the expression of miRNA and
      target pairs was used to determine putative miRNA targets. RESULTS: Analyses of
      our array data revealed distinct clusters of differentially expressed miRNAs that
      are specific to promyelocytes and granulocytes. While the roles of many of these
      miRNAs in granulopoiesis are not currently known, anti-correlation of the
      expression of miRNA/mRNA target pairs identified a suite of novel target genes.
      Clusters of miRNAs (including members of the let-7 and miR-17-92 families) are
      downregulated in hemopoietic stem/progenitor cells, potentially allowing the
      expression of target genes known to facilitate stem cell proliferation and
      homeostasis. Additionally, four miRNAs (miR-709, miR-706, miR-690 and miR-467a*)
      were found to be enriched in the nucleus of myeloid cells and multiple
      hemopoietic cell lines compared to other miRNAs, which are predominantly
      cytoplasmic-enriched. Both miR-709 and miR-706 are nuclear-enriched throughout
      granulopoiesis and have putative binding sites of extensive complementarity
      downstream of pri-miRNAs. Nuclear enrichment of miR-467a* is specific to
      hemopoietic stem/progenitors and promyelocytes. These miRNAs are also nuclear
      enriched in other hemopoietic cell lines, where nuclear sequestering may fine
      tune the expression of cytoplasmic mRNA targets. CONCLUSIONS: Overall, we have
      demonstrated differentially expressed miRNAs that have not previously been
      associated with hemopoietic differentiation and provided further evidence of
      regulated nuclear-enrichment of miRNAs. Further studies into miRNA function in
      granulocyte development may shed light on fundamental aspects of regulatory RNA
      biology and the role of nuclear miRNAs.

PMID- 24886829
TI  - Daughterless homodimer synergizes with Eyeless to induce Atonal expression and
      retinal neuron differentiation.
AB  - Class I Basic Helix-Loop-Helix (bHLH) transcription factors form homodimers or
      heterodimers with class II bHLH proteins. While bHLH heterodimers are known to
      have diverse roles, little is known about the role of class I homodimers. In this
      manuscript, we show that a linked dimer of Daughterless (Da), the only Drosophila
      class I bHLH protein, activates Atonal (Ato) expression and retinal neuron
      differentiation synergistically with the retinal determination factor Eyeless
      (Ey). The HLH protein Extramacrocheate (Emc), which forms heterodimer with Da,
      antagonizes the synergistic activation from Da but not the Da-Da linked dimer
      with Ey. We show that Da directly interacts with Ey and promotes Ey binding to
      the Ey binding site in the Ato 3' enhancer. Interestingly, the Ey binding site in
      the Ato 3' enhancer contains an embedded E-box that is also required for the
      synergistic activation by Ey and Da. Finally we show that mammalian homologs of
      Ey and Da can functionally replace their Drosophila counterparts to
      synergistically activate the Ato enhancer, suggesting that the observed function
      is evolutionary conserved. 

PMID- 24886833
TI  - Serotonin dynamics in and around the central nervous system: is autism solvable
      without fundamental insights?
AB  - Altered serotonin (5-hydroxytryptamine, 5-HT) signaling has been implicated in
      some developmental abnormalities of autism spectrum disorder (ASD). However, the
      presumed role of 5-HT in ASD raises new questions in fundamental neuroscience.
      Specifically, it is not clear if the current piecemeal approach to 5-HT signaling
      in the mammalian body is effective and whether new conceptual approaches may be
      required. This review briefly discusses 5-HT production and circulation in the
      central nervous system and outside of it, especially with regard to ASD, and
      proposes a more encompassing approach that questions the utility of the
      "neurotransmitter" concept. It then introduces the idea of a generalized 5-HT
      packet that may offer insights into possible links between serotonergic
      varicosities and blood platelets. These approaches have theoretical significance,
      but they are also well positioned to advance our understanding of some long
      standing problems in autism research. 

PMID- 24886834
TI  - Mouse strain and brain region-specific expression of the glutaminyl cyclases QC
      and isoQC.
AB  - Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate (pGlu) from
      glutamine precursors at the N-terminus of a number of peptide hormones,
      neuropeptides and chemokines. This post-translational modification stabilizes
      these peptides, protects them from proteolytical degradation or is important for
      their biological activity. However, QC is also involved in a pathogenic pGlu
      modification of peptides accumulating in protein aggregation disorders such as
      Alzheimer's disease and familial Danish and familial British dementia. Its
      isoenzyme (isoQC) was shown to contribute to aspects of inflammation by pGlu
      modifying and thereby stabilizing the monocyte chemoattractant protein CCL2. For
      the generation of respective animal models and for pharmacological treatment
      studies the characterization of the mouse strain and brain region-specific
      expression of QC and isoQC is indispensible. In order to address this issue, we
      used enzymatic activity assays and specific antibodies to detect both QC variants
      by immunohistochemistry in nine different mouse strains. Comparing different
      brain regions, the highest enzymatic QC/isoQC activity was detected in ventral
      brain, followed by cortex and hippocampus. Immunohistochemical stainings revealed
      that QC/isoQC activity in cortex mostly arises from isoQC expression. For most
      brain regions, the highest QC/isoQC activity was detected in C3H and FVB mice,
      whereas low QC/isoQC activity was present in CD1, SJL and C57 mice.
      Quantification of QC- and isoQC-immunoreactive cells by unbiased stereology
      revealed a higher abundance of isoQC- than of QC-immunoreactive neurons in
      Edinger-Westphal nucleus and in substantia nigra. In the locus coeruleus,
      however, there were comparable densities of QC- and of isoQC-immunoreactive
      neurons. These observations are of considerable importance with regard to the
      selection of appropriate mouse strains for the study of QC/isoQC relevance in
      mouse models of neurodegeneration and neuroinflammation and for the testing of
      therapeutical interventions in these models. 

PMID- 24886835
TI  - Light-mediated control of gene expression in filamentous fungus Trichoderma
      reesei.
AB  - We developed a light-mediated system based on synthetic light-switchable
      transactivators. The transactivators bind promoter upon blue-light exposure and
      rapidly initiate transcription of target transgenes in filamentous fungus
      Trichoderma reesei. Light is inexpensive to apply, easily delivered, and
      instantly removed, and thus has significant advantages over chemical inducers. 

PMID- 24886836
TI  - Understanding molecular identification and polyphasic taxonomic approaches for
      genetic relatedness and phylogenetic relationships of microorganisms.
AB  - The major proportion of earth's biological diversity is inhabited by
      microorganisms and they play a useful role in diversified environments. However,
      taxonomy of microorganisms is progressing at a snail's pace, thus less than 1% of
      the microbial population has been identified so far. The major problem associated
      with this is due to a lack of uniform, reliable, advanced, and common to all
      practices for microbial identification and systematic studies. However, recent
      advances have developed many useful techniques taking into account the house
      keeping genes as well as targeting other gene catalogues (16S rRNA, rpoA, rpoB,
      gyrA, gyrB etc. in case of bacteria and 26S, 28S, beta-tubulin gene in case of
      fungi). Some uncultivable approaches using much advanced techniques like flow
      cytometry and gel based techniques have also been used to decipher microbial
      diversity. However, all these techniques have their corresponding pros and cons.
      In this regard, a polyphasic taxonomic approach is advantageous because it
      exploits simultaneously both conventional as well as molecular identification
      techniques. In this review, certain aspects of the merits and limitations of
      different methods for molecular identification and systematics of microorganisms
      have been discussed. The major advantages of the polyphasic approach have also
      been described taking into account certain groups of bacteria as case studies to
      arrive at a consensus approach to microbial identification. 

PMID- 24886837
TI  - Efficient transformation of Rhizopus delemar by electroporation of germinated
      spores.
AB  - High efficient transformation of mycelial fungi is essential to both metabolic
      engineering and physiological analysis of these industrially important
      microorganisms. However, transformation efficiencies for mycelial fungi are
      highly restricted by difficulties in colony formation and competent cell
      preparation. In this work, an innovative transformation procedure that could
      significantly improve the efficiency of colony formation and transformation
      process has been established for a typical mycelial fungus, Rhizopus delemar.
      Single colonies of R. delemar were obtained with the addition of sodium
      deoxycholate. Fresh germinated spores of R. delemar were successfully transformed
      by electroporation. In addition, by pretreatment of the germinated spores with
      0.05M lithium acetate (LiAc) and 20mM dithiothreitol (DTT) before
      electroporation, the transformation efficiency was further improved by 9.5-fold.
      The final transformation efficiency at optimal conditions reached 1239
      transformants/MUg DNA. The method described here would facilitate more efficient
      metabolic engineering and investigation of physiological functions in R. delemar
      or other similar mycelial fungi. 

PMID- 24886839
TI  - Opportunities to enhance alternative sources of long-chain n-3 fatty acids within
      the diet.
AB  - Health benefits or advocated health benefits of long-chain (LC) n-3 PUFA are
      better known by medical doctors as well as by consumers, so that consumption
      increases. In addition, the development of aquaculture requires more fishmeal and
      fish oil. Humanisation of care of companion animals is also associated with
      addition of LC n-3 PUFA in pet foods. The risk of the increased demand for LC n-3
      PUFA is the excess harvesting of natural sources, especially of marine origin
      (oily fishes, krill). In order to improve sustainability, alternative sources of
      LC n-3 PUFA have been developed. These alternative sources are: (a) terrestrial
      plants naturally or genetically enriched in stearidonic acid (SDA), which
      bypasses the first limiting step of (i.e. ?6 desaturase) of the biosynthesis of
      LC n-3 PUFA; (b) single-cell oils rich in LC n-3 PUFA (microalgae, Escherichia
      coli) and krill. Currently, plants rich in SDA are expensive, metabolic
      engineering is unfavourably accepted by consumers in many countries, cultivation
      of microalgae is very expensive even though their ability (for some of them) to
      synthesise biofuels could induce a decrease in industrial costs, and Antarctic
      krill harvest must be restricted. Thus, it is difficult to predict their real
      development in the future. 

PMID- 24886838
TI  - Secondary prevention trials in Alzheimer disease: the challenge of identifying a
      meaningful end point.

PMID- 24886840
TI  - Design and analysis of a Petri net model of the Von Hippel-Lindau (VHL) tumor
      suppressor interaction network.
AB  - Von Hippel-Lindau (VHL) syndrome is a hereditary condition predisposing to the
      development of different cancer forms, related to germline inactivation of the
      homonymous tumor suppressor pVHL. The best characterized function of pVHL is the
      ubiquitination dependent degradation of Hypoxia Inducible Factor (HIF) via the
      proteasome. It is also involved in several cellular pathways acting as a
      molecular hub and interacting with more than 200 different proteins. Molecular
      details of pVHL plasticity remain in large part unknown. Here, we present a novel
      manually curated Petri Net (PN) model of the main pVHL functional pathways. The
      model was built using functional information derived from the literature. It
      includes all major pVHL functions and is able to credibly reproduce VHL syndrome
      at the molecular level. The reliability of the PN model also allowed in silico
      knockout experiments, driven by previous model analysis. Interestingly, PN
      analysis suggests that the variability of different VHL manifestations is
      correlated with the concomitant inactivation of different metabolic pathways. 

PMID- 24886841
TI  - High throughput mutagenesis for identification of residues regulating human
      prostacyclin (hIP) receptor expression and function.
AB  - The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein
      coupled receptor (GPCR) that plays a critical role in vascular smooth muscle
      relaxation and platelet aggregation. hIP receptor dysfunction has been implicated
      in numerous cardiovascular abnormalities, including myocardial infarction,
      hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered
      several genetic variations in the PTGIR gene coding for hIP receptor, however,
      its structure-function relationship has not been sufficiently explored. Here we
      set out to investigate the applicability of high throughput random mutagenesis to
      study the structure-function relationship of hIP receptor. While chemical
      mutagenesis was not suitable to generate a mutagenesis library with sufficient
      coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a
      valuable method for the unbiased screening of residues regulating hIP receptor
      function and expression. Here we describe the generation and functional
      characterization of an epPCR derived mutagenesis library compromising >4000
      mutants of the hIP receptor. We introduce next generation sequencing as a useful
      tool to validate the quality of mutagenesis libraries by providing information
      about the coverage, mutation rate and mutational bias. We identified 18 mutants
      of the hIP receptor that were expressed at the cell surface, but demonstrated
      impaired receptor function. A total of 38 non-synonymous mutations were
      identified within the coding region of the hIP receptor, mapping to 36 distinct
      residues, including several mutations previously reported to affect the signaling
      of the hIP receptor. Thus, our data demonstrates epPCR mediated random
      mutagenesis as a valuable and practical method to study the structure-function
      relationship of GPCRs. 

PMID- 24886842
TI  - Functional effects of Toll-like receptor (TLR)3, 7, 9, RIG-I and MDA-5
      stimulation in nasal epithelial cells.
AB  - BACKGROUND: The human nasal epithelium is an important physical barrier, and a
      part of the innate immune defense that protect against pathogens. The epithelial
      cells recognize microbial components by pattern-recognition receptors (PRRs), and
      thereby trigger an immune response. Even though TLR3, TLR7, TLR9, RIG-I and MDA-5
      are all known to respond to viral stimulation, their potential role in chronic
      airway inflammation triggered by local cytokine release remains to be
      established. METHODS: mRNA and corresponding protein expression of TLR3, TLR7,
      TLR9, RIG-I and MDA-5 were analyzed in nasal biopsies and various upper airway
      epithelial cell lines using real-time reverse transcription PCR,
      immunohistochemistry and flow cytometry. Ligand induced, cytokine release, was
      evaluated with ELISA. RESULTS: Nasal biopsies were found to express TLR3, TLR7,
      TLR9, RIG-I and MDA-5, with the most abundant expression in the surface
      epithelium. These receptors were verified in primary human nasal epithelial cell
      (HNEC) as well as in the airway epithelial cell lines Detroit-562 and FaDu.
      Poly(I:C) (TLR3) and R-837 (TLR7) stimulation increased secretion of IL-6 and GM
      CSF from the nasal mucosa and the epithelial cell lines. CpG (TLR9) stimulation
      caused release of IL-8 in the nasal mucosa and in FaDu. Poly(I:C)/LyoVec (RIG
      I/MDA-5) stimulation activated the secretion of IFN-beta in the nasal mucosa. A
      corresponding release was also detected from HNEC and Detroit-562. CONCLUSION:
      The nasal epithelium has the ability to recognize viral intrusion through TLR and
      RLR receptors, and the subsequent response might have a role in exacerbation of
      inflammatory diseases like allergic rhinitis and chronic rhinosinusitis.

PMID- 24886844
TI  - Traumatic and other non-natural childhood deaths in Manitoba, Canada: a
      retrospective autopsy analysis (1989-2010).
AB  - OBJECTIVE: The goals of analyzing all non-natural childhood deaths in Manitoba
      for the 22-year period (1989-2010) are to highlight preventable causes of death
      and to document temporal trends that might be influenced by changes in society.
      METHODS: The 1989 to 2010 pediatric autopsy database at the Winnipeg Health
      Sciences Centre and records from the Office of the Chief Medical Examiner were
      searched for all non-natural deaths <= 18 years age. All files were reviewed in
      detail. Data collected included demographic characteristics, manner of death,
      details of cause and circumstances leading to death, and survival time after the
      event. RESULTS: For the 22-year period, the total number of non-natural childhood
      deaths after which autopsy was performed in Manitoba was 581 for males and 409
      for females in a population of approximately 1.23 million (2010 estimate). This
      represents 22.1% of the total childhood deaths in Manitoba during the study
      period. A higher proportion of children living in rural and northern communities
      died from non-natural causes. Of all accidents, which peaked in 1999, road
      traffic incidents accounted for the majority. Of suicides, which peaked in 2005,
      hanging in the 15-18 year group accounted for almost all cases. Of homicides,
      child abuse deaths at <3 years age was the most frequent cause. For all causes,
      most individuals were dead at the scene or died shortly thereafter. CONCLUSIONS:
      Most non-natural childhood deaths in Manitoba might be avoidable through
      education about prevention strategies and by correction of social inequities.
      Improved transportation to hospital from remote locations would likely have
      little impact on survival.

PMID- 24886843
TI  - Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with
      multiple sclerosis.
AB  - BACKGROUND: Soluble CD163 (sCD163) is a macrophage specific protein known to be
      up-regulated in serum from patients with multiple sclerosis (MS). OBJECTIVE: To
      investigate sCD163 in serum and CSF (cerebrospinal fluid) from patients
      undergoing MS diagnostic work-up and analyse its potential as a diagnostic
      biomarker. METHODS: After a full MS diagnostic work-up, including collection of
      paired samples of CSF and serum, 183 patients were evaluated for inclusion in
      this study. Patients were divided into groups based on their diagnosis. Patients
      with normal clinical and paraclinical findings were grouped as symptomatic
      controls. Serum and CSF levels of sCD163 were determined by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: sCD163 could be measured in all serum and
      CSF samples. A high sCD163 CSF/serum ratio in relation to molecular weight was
      found, strongly indicating local production in the CNS. Median levels of sCD163
      were significantly decreased in serum and significantly elevated in CSF in
      patients with relapsing-remitting, and primary-progressive MS. There were,
      however, some overlaps of the measures between groups. In a receiver operating
      characteristic (ROC) analysis sCD163 CSF/serum ratio had an area under the curve
      of 0.72. CONCLUSION: The sCD163 CSF/serum ratio was significantly increased in
      patients with MS and may reflect macrophage activation in MS lesions. These
      results suggest that primary progressive MS also is driven by inflammation in
      which the innate immune system plays a pivotal role.

PMID- 24886845
TI  - Roles of physical and mental health in suicidal ideation in Canadian Armed Forces
      Regular Force veterans.
AB  - OBJECTIVES: Suicide in recent veterans is an international concern. An
      association between mental disorders and suicide has been established, but less
      information is available about an association between physical health problems
      and suicide among veterans. This study extends this area of inquiry by examining
      the relationship of both physical and mental health problems with suicidal
      ideation in a representative national sample of Canadian veterans. METHODS:
      Subjects were a stratified random sample of 2,658 veterans who had been released
      from the Canadian Armed Forces Regular Force during 1998-2007 and had
      participated in the 2010 Survey on Transition to Civilian Life. Associations
      between physical and mental health and past-year suicidal ideation were explored
      in multivariable regression models using three measures of physical and mental
      health. RESULTS: The prevalence of suicidal ideation was 5.8% (95% confidence
      interval [CI]: 5.0%-6.8%). After adjustment for covariates, ideation was
      associated with gastrointestinal disorders (adjusted odds ratio [AOR] 1.66, CI:
      1.03-2.65), depression or anxiety (AOR 5.06, CI: 2.97-8.62) and mood disorders
      (AOR 2.91, CI: 1.67-5.07); number of physical (AOR 1.22, CI: 1.05-1.42) and
      mental conditions (AOR 2.32, CI: 2.01-2.68); and SF-12 Health Survey physical
      health (AOR 0.98, CI: 0.96-0.99 for each 1 point increase) and mental health (AOR
      0.88, CI: 0.87-0.89). CONCLUSIONS: Physical health was independently associated
      with suicidal ideation after adjustment for mental health status and socio
      demographic characteristics. The findings underscore the importance of
      considering physical health in population-based suicide prevention efforts and in
      mitigating suicide risk in individual veterans.

PMID- 24886846
TI  - Chlamydia trachomatis epidemiology in Canadians of Chinese ethnicity: a
      population-based study.
AB  - OBJECTIVES: To compare the rates of Chlamydia trachomatis infection between those
      of Chinese ethnicity and non-Chinese ethnicity in a large Canadian urban setting.
      METHODS: We examined rates of Chlamydia among residents of Vancouver and
      Richmond, Canada, by Chinese and non-Chinese ethnicity, from 2006 to 2010. We
      stratified cases by age group, sex and ethnicity. We analyzed 12,555 cases of
      Chlamydia from 2006 to 2010. RESULTS: The overall rate of Chlamydia was 276 per
      100,000 per year. Chlamydia rates were 236 per 100,000 among those of Chinese
      ethnicity and 338 per 100,000 among non-Chinese. While overall rates among
      individuals of Chinese ethnicity were lower, rates among older Chinese women were
      significantly higher than among their non-Chinese counterparts. CONCLUSIONS:
      Physicians serving patients of Chinese ethnicity should be aware that rates among
      Chinese-Canadians are substantial, with rates among older women higher than among
      non-Chinese women, and they should consider this when screening for sexually
      transmitted infections in this population. Further research is needed to
      elucidate why this is the case.

PMID- 24886847
TI  - Recreational use of prescription medications among Canadian young people:
      identifying disparities.
AB  - OBJECTIVES: While the recreational use of prescription medications is widely
      recognized as a growing public health issue, there are limited epidemiological
      studies on patterns of use in Canada, particularly studies identifying
      populations at highest risk. The objective of this study was to describe
      recreational prescription drug use among Canadian adolescents by age, sex, socio
      economic, immigration and geographic status. METHODS: Data were obtained from
      grade 9 and 10 students participating in the 2009/2010 cycle of the nationally
      representative Canadian Health Behaviour in School-aged Children study
      (n=10,429). Students were asked about past-year recreational use of pain
      relievers, stimulants and sedative/tranquilizer medications. Cross-tabulations
      and multi-level Poisson regression were conducted to evaluate the prevalence of
      use and to explore disparities. RESULTS: Approximately 7% of students reported
      past-year recreational use of one or more prescription medication(s). Females
      reported 1.25 times the risk of recreational use of pain relievers as compared
      with males (95% confidence interval [CI]: 1.04-1.51). Students of lower socio
      economic status (SES) were 2.41 times more likely to report recreational use of
      any type of medication (95% CI: 1.94-2.99). Recreational use of pain reliever
      medications was highest among rural youth living in close proximity to urban
      centres. Rates for all medications were similar between immigrant and non
      immigrant students. CONCLUSIONS: Recreational prescription drug use
      disproportionately affects certain subgroups of youth, including females, those
      of lower SES and those in some rural settings more than others. These results
      provide foundational data to inform preventive efforts aimed at management of the
      nonmedical use and divergence of prescription medications.

PMID- 24886849
TI  - Inuit family understandings of sexual health and relationships in Nunavut.
AB  - OBJECTIVE: To explore Inuit family understandings of sexual health and
      relationships in order to inform responsive public health interventions that are
      designed to meet the needs of Nunavummiut. METHOD: A qualitative indigenous
      knowledge approach was used for this study with a focus on Inuit epistemology and
      methodology, as described in the Piliriqatigiinniq Community Health Research
      Partnership Model. Interviews were conducted with 20 parents in three Nunavut
      communities in 2011. An immersion and crystallization analytical approach was
      used to analyze the data and to identify groupings or themes in the data. The
      stories shared by parents are honoured, keeping their words intact as often as
      possible in the presentation of results. RESULTS: Parents in this study largely
      discussed sexual health in the context of historical community events related to
      settlement and/or residential schools. Residential schools and forced settlement
      into communities were linked to trauma, family separation, hardship and grief.
      These experiences were prominent in participants' understandings of sexual health
      and perceptions of sexual health behaviours among youth in the community.
      CONCLUSION: This study highlights the complexity of the landscape of sexual
      health in Nunavut and the need for public health approaches that are inclusive of
      Inuit family perspectives on sexual health. Greater understanding of historical
      and community context can contribute to the development of pertinent, evidence
      based public health interventions that will meet the needs of the population.

PMID- 24886848
TI  - Examining the effects of increased vitamin D fortification on dietary inadequacy
      in Canada.
AB  - OBJECTIVES: Despite mandatory fortification of milk and margarine, most Canadians
      have inadequate vitamin D intake and consequently poor vitamin D status,
      especially in the winter. Increasing vitamin D fortification is one possible
      strategy to address this inadequacy. The purpose of our study was to examine the
      modelled effect of increased vitamin D fortification on the prevalence of
      inadequacy and the percentage of intakes greater than the Tolerable Upper Intake
      Level (UL) using different fortification scenarios. METHODS: Dietary intakes (24
      h recall) from the 2004 Canadian Community Health Survey 2.2 (n=34,381) were used
      to model increased vitamin D levels in milk and the addition of vitamin D to
      cheese and yogurt at various levels to meet label claims of an "excellent source"
      based on the recommended dietary intakes. The Software for Intake Distribution
      Evaluation was used to estimate the prevalence of inadequacy and intakes >UL.
      RESULTS: Fortification of milk, yogurt and cheese at 6.75 MUg (270 IU)/serving
      led to more than doubling of vitamin D intakes across all sex/age groups and a
      drop in the prevalence of dietary inadequacy from >80% to <50% in all groups.
      Furthermore, no intakes approached the UL under any fortification scenario in any
      sex/age group. CONCLUSION: There is a pressing need to improve vitamin D status
      among Canadians. Increasing vitamin D fortification of dairy products, consistent
      with their positioning in Canada's Food Guide, can lead to increased intake
      without a risk of excess. This is a population-wide public health strategy that
      should be given consideration in Canada.

PMID- 24886850
TI  - Municipal-level responses to household food insecurity in Canada: a call for
      critical, evaluative research.
AB  - Household food insecurity (HFI) is a persistent public health problem affecting
      3.8 million Canadians. While the causes of HFI are rooted in income insecurity,
      solutions to HFI have been primarily food-based, with the bulk of activity
      occurring at the municipal level across Canada. We conceptualize these municipal
      level actions as falling within three models: "charitable", "household
      improvements and supports" and "community food systems". Many initiatives,
      especially non-charitable ones, generate widespread support, as they aim to
      increase participants' food security using an empowering and dignified approach.
      While these initiatives may offer some benefits to their participants,
      preliminary research suggests that any food-based solution to an income-based
      problem will have limited reach to food-insecure households and limited impact on
      participants' experience of HFI. We suspect that widespread support for the local
      level food-based approach to HFI has impeded critical judgement of the true
      potential of these activities to reduce HFI. As these initiatives grow in number
      across Canada, we are in urgent need of comprehensive and comparative research to
      evaluate their impact on HFI and to ensure that municipal-level action on HFI is
      evidence-based. 

PMID- 24886851
TI  - [Solutions for the better integration of public health ethical considerations].
AB  - Public Health Ethics (PHE) has grown significantly during the past decade.
      Despite PHE's relevance, its integration into public health practices, resources,
      activities and knowledge is lacking. In our view, this lack of integration can be
      understood as a problem of knowledge transfer (KT). In this article, we briefly
      describe existing knowledge integration methods and their limitations for PHE. We
      then explore the KT literature to underline how recent research in this area
      presents possible solutions to the problem before us. The proposed solutions
      stress the importance, first, of adapting knowledge and tools to the needs of
      users and the context of their practice, and, second, of recognizing the
      personal, continual nature of interactions between actors. We conclude that it
      would be beneficial to public health organizations to count on the presence and
      expertise of PHE knowledge brokers in order to build, in partnership with
      knowledge users, tools that will allow them to achieve PHE integration in public
      health practices, resources, activities and knowledge.

PMID- 24886852
TI  - Non-medical prescription opioid use, prescription opioid-related harms and public
      health in Canada: an update 5 years later.
AB  - Five years ago, we highlighted Canada's emerging problem of prescription opioid
      (PO)-related harms and emphasized the need for targeted surveillance, research
      and interventions. Overall levels of PO use in the Canadian population have grown
      by 70% since then, while at the same time levels of non-medical PO use (NMPOU) in
      general and in key risk populations have continued to be high; furthermore, PO
      related harms - specifically morbidity (e.g., treatment admissions) and mortality
      (e.g., overdose deaths) - have risen substantively. Unfortunately, major
      knowledge gaps related to systematic monitoring of PO-related harms continue to
      exist; for example, no national morbidity or mortality statistics are available.
      Investigator-driven research has generated important insights into the
      epidemiology and impacts of PO-related harms: high correlations between
      population-level PO dispensing and/or PO dosing and harms; high rates of co
      occurrence of NMPOU and co-morbidities; and distinct NMPOU-related risk dynamics
      among street drug users. Select policy measures have been implemented only
      recently at the federal and provincial levels; these interventions remain to be
      systematically evaluated, especially given preliminary indications of reductions
      in PO-related harms (e.g., NMPOU) unfolding prior to the interventions. For these
      purposes, improvements in surveillance tools and research resources devoted to
      the extensive public health problem of PO-related harms in Canada continue to be
      urgently needed. 

PMID- 24886853
TI  - A vision for chronic disease prevention intervention research: report from a
      workshop.
AB  - The Population Studies Research Network of Cancer Care Ontario hosted a strategic
      planning workshop to establish an agenda for a prevention intervention research
      program in Ontario, including priority topics for investigation and design
      considerations. The two-day workshop included: presentations on background papers
      developed to facilitate participants' preparation for and discussions in the
      workshop; keynote presentations on intervention research concerning primary
      prevention of chronic diseases, design and study implementation considerations; a
      dedicated session on critical and creative thinking to stimulate participation
      and discussion topics; break out groups to identify, discuss and present study
      ideas, designs, implementation considerations; and a consensus process to discuss
      and identify recommendations for research priorities and next steps. The retreat
      yielded the following recommendations: 1) develop an intervention research agenda
      that includes working with existing large-scale cohorts; 2) develop an
      intervention research agenda that includes novel research designs that could
      target individuals or groups; and 3) develop an intervention research agenda in
      which studies collect data on costs, define stakeholders, and ensure clear
      strategies for stakeholder engagement and knowledge transfer. The Population
      Studies Research Network will develop options from these recommendations and
      release a call for proposals in 2014 for intervention research pilot projects
      that reflect these recommendations. Pilot projects will be evaluated based on
      their fit with the retreat's recommendations, and their potential to scale up to
      full studies and application in practice.

PMID- 24886854
TI  - Improved obesity prevalence estimates for Atlantic Canada.

PMID- 24886855
TI  - E-cigarettes - promise or peril?

PMID- 24886857
TI  - Modeling and roles of meteorological factors in outbreaks of highly pathogenic
      avian influenza H5N1.
AB  - The highly pathogenic avian influenza A virus subtype H5N1 (HPAI H5N1) is a
      deadly zoonotic pathogen. Its persistence in poultry in several countries is a
      potential threat: a mutant or genetically reassorted progenitor might cause a
      human pandemic. Its world-wide eradication from poultry is important to protect
      public health. The global trend of outbreaks of influenza attributable to HPAI
      H5N1 shows a clear seasonality. Meteorological factors might be associated with
      such trend but have not been studied. For the first time, we analyze the role of
      meteorological factors in the occurrences of HPAI outbreaks in Bangladesh. We
      employed autoregressive integrated moving average (ARIMA) and multiplicative
      seasonal autoregressive integrated moving average (SARIMA) to assess the roles of
      different meteorological factors in outbreaks of HPAI. Outbreaks were modeled
      best when multiplicative seasonality was incorporated. Incorporation of any
      meteorological variable(s) as inputs did not improve the performance of any
      multivariable models, but relative humidity (RH) was a significant covariate in
      several ARIMA and SARIMA models with different autoregressive and moving average
      orders. The variable cloud cover was also a significant covariate in two SARIMA
      models, but air temperature along with RH might be a predictor when moving
      average (MA) order at lag 1 month is considered. 

PMID- 24886856
TI  - Electronic cigarettes in Canada: prevalence of use and perceptions among youth
      and young adults.
AB  - OBJECTIVES: The goal of this study was to examine the prevalence and perceptions
      of electronic cigarette use among Canadian youth and young adults. METHODS: A
      sample of 1,188 youth and young adults age 16-30 years were recruited from an
      online panel of Canadians in 2012. After viewing an image of an e-cigarette,
      respondents answered questions regarding their use and perceptions of e
      cigarettes. RESULTS: Close to half of respondents (43.4%) had seen e-cigarettes
      advertised or for sale. A total of 16.1% reported trying an e-cigarette (5.2%
      nonsmokers, 18.9% former smokers, and 34.5% current smokers), and 5.7% reported
      use in the past 30 days (0.8% non-smokers, 1.4% former smokers, and 15.0% current
      smokers). Compared to non-smokers, former smokers and current smokers were more
      likely to have tried e-cigarettes (OR=4.25 and OR=9.84, respectively), and
      current smokers were more likely to have tried e-cigarettes than former smokers
      (OR=2.32). Current smokers were also more likely to be current users of e
      cigarettes than both former smokers (OR=15.15) and non-smokers (OR=4.43). Smokers
      were interested in trying e-cigarettes to help them quit smoking (80.4%), as a
      long-term replacement for cigarettes (77.8%), or to use in places where they
      cannot smoke (80.9%). CONCLUSIONS: Awareness of e-cigarettes among surveyed youth
      and young adults is quite high. Almost one fifth (16.1%) of participants reported
      trying e-cigarettes, with evidence of use among non-smokers.

PMID- 24886858
TI  - Flow analysis in Brazil: contributions over the last four decades.
AB  - The main contributions of Brazilian researchers to the field of flow analysis are
      reviewed, with an emphasis on historical developments, conceptual aspects, system
      design, and analytical applications. Contributions after the advent of flow
      injection analysis are highlighted. Novel approaches (e.g. zone merging, zone
      sampling, zone trapping, multi-site detection, and multi-commutation), flow
      modalities (e.g. monosegmented flow analysis, flow-batch analysis, multi-pumping
      flow analysis), as well as the pioneering implementation of different detection
      techniques (e.g. potentiometry, turbidimetry, flame atomic absorption
      spectrometry, inductively coupled plasma-optical emission spectrometry, and
      gravimetry) and analytical steps (e.g. titrations, membrane-less gas diffusion,
      and electrolytic dissolution) are highlighted. Strategies to improve analytical
      figures of merit and the use of the flow analyser as a tool for teaching purposes
      are also discussed. Contributions from Brazilian workers in the context of system
      miniaturization, "green" chemistry, analysis of complex samples, novel strategies
      and materials for in-line analyte separation/concentration, and proposals for
      expert systems are also highlighted. The large-scale analysis of samples of
      agronomical, environmental, industrial, and clinical relevance is emphasized. 

PMID- 24886860
TI  - Scandium versus yttrium{amino-alkoxy-bis(phenolate)} complexes for the
      stereoselective ring-opening polymerization of racemic lactide and beta
      butyrolactone.
AB  - Scandium and yttrium amide complexes Ln{ONXO(R1,R2)}(N(SiHMe2)2)(THF)n (Ln = Sc,
      n = 0 or Y, n = 1; X = NMe2 or OMe; R(1) = Cumyl or p-Cl-Cumyl; R(2) = Me or
      Cumyl) were prepared by aminolysis of Ln[N(SiHMe2)2]3(THF) with the corresponding
      tetradentate diamino- or alkoxy-amino-bis(phenol) pro-ligands {ONXO(R1,R2)}H2. In
      the solid state and in toluene solution, the scandium complexes are monomeric and
      5-coordinated, while the analogous yttrium complexes all bear an extra THF
      coordinated molecule and are 6-coordinated. Sc{ONXO(R1,R2)}(N(SiHMe2)2) complexes
      are single-site initiators for the ring-opening polymerization (ROP) of racemic
      lactide but are less active than their yttrium analogues
      Y{ONXO(R1,R2)}(N(SiHMe2)2)(THF); also, in contrast to the latter ones, they are
      inactive in the ROP of the more demanding racemic beta-butyrolactone. On the
      other hand, the scandium amide complexes feature a significantly improved control
      over the ROP of lactide, yielding PLAs with much narrower molecular weight
      distributions (D(M) < 1.1 for Sc vs. 1.5-2.0 for Y). The yttrium complex with the
      very bulky o,p-dicumyl-substituted ligand is more heteroselective than its
      scandium analogue (P(r) = 0.88 vs. 0.83), while the opposite is observed with
      complexes based on p-methyl-substituted ligands (P(r) = 0.50 in toluene or 0.72
      0.75 in THF for Y vs. P(r) = 0.75-0.83 for Sc in toluene). These reactivity and
      selectivity trends are rationalized by a much more sterically crowded
      coordination sphere in scandium than in yttrium complexes.

PMID- 24886859
TI  - Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9
      contributes to interleukin 1beta-induced microsomal prostaglandin E synthase 1
      expression in human osteoarthritic chondrocytes.
AB  - INTRODUCTION: Microsomal prostaglandin E synthase 1 (mPGES-1) catalyzes the
      terminal step in the biosynthesis of PGE2, a critical mediator in the
      pathophysiology of osteoarthritis (OA). Histone methylation plays an important
      role in epigenetic gene regulation. In this study, we investigated the roles of
      histone H3 lysine 9 (H3K9) methylation in interleukin 1beta (IL-1beta)-induced
      mPGES-1 expression in human chondrocytes. METHODS: Chondrocytes were stimulated
      with IL-1beta, and the expression of mPGES-1 mRNA was evaluated using real-time
      RT-PCR. H3K9 methylation and the recruitment of the histone demethylase lysine
      specific demethylase 1 (LSD1) to the mPGES-1 promoter were evaluated using
      chromatin immunoprecipitation assays. The role of LSD1 was further evaluated
      using the pharmacological inhibitors tranylcypromine and pargyline and small
      interfering RNA (siRNA)-mediated gene silencing. The LSD1 level in cartilage was
      determined by RT-PCR and immunohistochemistry. RESULTS: The induction of mPGES-1
      expression by IL-1beta correlated with decreased levels of mono- and dimethylated
      H3K9 at the mPGES-1 promoter. These changes were concomitant with the recruitment
      of the histone demethylase LSD1. Treatment with tranylcypromine and pargyline,
      which are potent inhibitors of LSD1, prevented IL-1beta-induced H3K9
      demethylation at the mPGES-1 promoter and expression of mPGES-1. Consistently,
      LSD1 gene silencing with siRNA prevented IL-1beta-induced H3K9 demethylation and
      mPGES-1 expression, suggesting that LSD1 mediates IL-1beta-induced mPGES-1
      expression via H3K9 demethylation. We show that the level of LSD1 was elevated in
      OA compared to normal cartilage. CONCLUSION: These results indicate that H3K9
      demethylation by LSD1 contributes to IL-1beta-induced mPGES-1 expression and
      suggest that this pathway could be a potential target for pharmacological
      intervention in the treatment of OA and possibly other arthritic conditions.

PMID- 24886861
TI  - Combination treatment of tamoxifen with risperidone in breast cancer.
AB  - Tamoxifen has long been used and still is the most commonly used endocrine
      therapy for treatment of both early and advanced estrogen receptor-positive
      breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic
      effect primarily through cytostasis which is associated with the accumulation of
      cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be
      exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3,
      and poly-ADP-ribose polymerase (PARP). Down-regulation of anti-apoptotic proteins
      Bcl-2 and Bcl-xL and up-regulation of pro-apoptotic proteins Bax and Bak have
      also been observed. In addition, stress response protein of GRP 94 and GRP 78
      have also been induced by tamoxifen in our study. However, side effects occur
      during tamoxifen treatment in breast cancer patients. Researching into
      combination regimen of tamoxifen and drug(s) that relieves tamoxifen-induced hot
      flushes is important, because drug interactions may decrease tamoxifen efficacy.
      Risperidone has been shown to be effective in reducing or eliminating hot flushes
      on women with hormonal variations. In this present study, we demonstrated that
      combination of tamoxifen with risperidone did not interfered tamoxifen-induced
      cytotoxic effects in both in vitro and in vivo models, while fluoxetine abrogated
      the effects of tamoxifen. This is the first paper suggesting the possibility of
      combination treatment of tamoxifen with risperidone in breast cancer patients,
      providing a conceivable resolution of tamoxifen-induced side effects without
      interfering the efficacy of tamoxifen against breast cancer. 

PMID- 24886862
TI  - Protocol for a systematic review of the association between chronic stress during
      the life course and telomere length.
AB  - BACKGROUND: The effects of stress on ill health have become evident in recent
      years. Under acute stress situations, a cascade of physiological events helps the
      body mount an appropriate adaptive response. However, under chronic stress
      situations, this physiological response may lead to wear and tear on the body
      that accelerates the decline in physiological functioning and increases the risk
      of chronic conditions. Recent evidence for social stress experienced during
      childhood suggests serious consequences many years later, even later life.
      Telomere length, a marker of cell aging, may provide a link between chronic
      social stress and age-associated physical and mental decline and risk of chronic
      conditions. This study examines whether chronic social stress is associated with
      telomere length throughout the life course. METHODS/DESIGN: We will perform a
      systematic review of the literature on the relationship between chronic social
      stress, for example, due to violence, extreme poverty, or caregiving of people
      with disabling conditions (exposure), and telomere length (outcome) by searching
      electronic databases in MEDLINE (PubMed interface), EMBASE (OVID interface),
      Cochrane Central (OVID interface) and gray literature from their start date
      onwards. We will limit the search to studies performed on human populations. Two
      reviewers will conduct standardized screening, eligibility assessment, data
      abstraction, and scientific quality assessment. All study designs investigating
      the association between chronic social stress and telomere length in healthy or
      diseased adults and children will be eligible for inclusion in the review. We
      will extract individual demographic and socioeconomic characteristics, research
      setting, method of measuring telomere length, reported outcome, and determinants
      of interest. Studies will also be stratified by 1) age into 3 groups: childhood
      (0 to 18 years), adulthood (19 to 64 years) and late life (65+); 2) cell type; 3)
      study design; and 4) telomere length assessment method. Where feasible, study
      results will be combined through meta-analyses to obtain a pooled measure of
      associations. Results will be reported according to the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) Statement. DISCUSSION: This
      systematic review will provide knowledge on the existing evidence for chronic
      social stress and its association with telomere lengths throughout the life
      course.

PMID- 24886863
TI  - Post-heparin LPL activity measurement using VLDL as a substrate: a new robust
      method for routine assessment of plasma triglyceride lipolysis defects.
AB  - BACKGROUND: Determination of lipoprotein lipase (LPL) activity is important for
      hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with
      current methods. Consequently by using human VLDL as substrate we developed a new
      LPL assay which does not require sonication, radioactive or fluorescent
      particles. METHODS: Post-heparin plasma was added to the VLDL substrate prepared
      by ultracentrifugation of heat inactivated normolipidemic human serums, diluted
      in buffer, pH 8.15. Following incubation at 37 degrees c, the NEFA (non
      esterified fatty acids) produced were assayed hourly for 4 hours. LPL activity
      was expressed as umol/l/min after subtraction of hepatic lipase (HL) activity,
      obtained following LPL inhibition with NaCl 1.5 mmol/l. Molecular analysis of
      LPL, GPIHBP1, APOA5, APOC2, APOE genes was available for 62 patients. RESULTS:
      Our method was reproducible (coefficient of variation (CV): intra-assay 5.6%,
      inter-assay 7.1%), and tightly correlated with the conventional radiolabelled
      triolein emulsion method (n = 26, r = 0.88). Normal values were established at
      34.8 +/- 12.8 umol/l/min (mean +/- SD) from 20 control subjects. LPL activities
      obtained from 71 patients with documented history of major hypertriglyceridemia
      showed a trimodal distribution. Among the 11 patients with a very low LPL
      activity (< 10 umol/l/min), 5 were homozygous or compound heterozygous for LPL or
      GPIHBP1 deleterious mutations, 3 were compound heterozygous for APOA5 deleterious
      mutations and the p.S19W APOA5 susceptibility variant, and 2 were free of any
      mutations in the usual candidate genes. No homozygous gene alteration in LPL,
      GPIHBP1 and APOC2 genes was found in any of the patients with LPL activity > 10
      umol/l/min. CONCLUSION: This new reproducible method is a valuable tool for
      routine diagnosis and reliably identifies LPL activity defects.

PMID- 24886864
TI  - Coefficient of glucose variation is independently associated with mortality in
      critically ill patients receiving intravenous insulin.
AB  - INTRODUCTION: Both patient- and context-specific factors may explain the
      conflicting evidence regarding glucose control in critically ill patients. Blood
      glucose variability appears to correlate with mortality, but this variability may
      be an indicator of disease severity, rather than an independent predictor of
      mortality. We assessed blood glucose coefficient of variation as an independent
      predictor of mortality in the critically ill. METHODS: We used eProtocol-Insulin,
      an electronic protocol for managing intravenous insulin with explicit rules, high
      clinician compliance, and reproducibility. We studied critically ill patients
      from eight hospitals, excluding patients with diabetic ketoacidosis and patients
      supported with eProtocol-insulin for < 24 hours or with < 10 glucose
      measurements. Our primary clinical outcome was 30-day all-cause mortality. We
      performed multivariable logistic regression, with covariates of age, gender,
      glucose coefficient of variation (standard deviation/mean), Charlson comorbidity
      score, acute physiology score, presence of diabetes, and occurrence of
      hypoglycemia < 60 mg/dL. RESULTS: We studied 6101 critically ill adults.
      Coefficient of variation was independently associated with 30-day mortality (odds
      ratio 1.23 for every 10% increase, P < 0.001), even after adjustment for
      hypoglycemia, age, disease severity, and comorbidities. The association was
      higher in non-diabetics (OR = 1.37, P < 0.001) than in diabetics (OR 1.15, P =
      0.001). CONCLUSIONS: Blood glucose variability is associated with mortality and
      is independent of hypoglycemia, disease severity, and comorbidities. Future
      studies should evaluate blood glucose variability.

PMID- 24886866
TI  - Violapyrones H and I, new cytotoxic compounds isolated from Streptomyces sp.
      associated with the marine starfish Acanthaster planci.
AB  - Two new alpha-pyrone derivatives, violapyrones H (1) and I (2), along with known
      violapyrones B (3) and C (4) were isolated from the fermentation broth of a
      marine actinomycete Streptomyces sp. The strain was derived from a crown-of
      thorns starfish, Acanthaster planci, collected from Chuuk, Federated States of
      Micronesia. The structures of violapyrones were elucidated by the analysis of 1D
      and 2D NMR and HR-ESIMS data. Violapyrones (1-4) exhibited cytotoxicity against
      10 human cancer cell lines with GI50 values of 1.10-26.12 MUg/mL when tested
      using sulforhodamine B (SRB) assay. This is the first report on the cytotoxicity
      of violapyrones against cancer cell lines and the absolute configuration of
      violapyrone C. 

PMID- 24886867
TI  - The protective effect of fucoidan in rats with streptozotocin-induced diabetic
      nephropathy.
AB  - Diabetic nephropathy (DN) has long been recognized as the leading cause of end
      stage renal disease, but the efficacy of available strategies for the prevention
      of DN remains poor. The aim of this study was to investigate the possible
      beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in
      rats. Wistar rats were made diabetic by injection of STZ after removal of the
      right kidney. FPS was administered to these diabetic rats for 10 weeks. Body
      weight, physical activity, renal function, and renal morphometry were measured
      after 10 weeks of treatment. In the FPS-treated group, the levels of blood
      glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum
      insulin and the beta2-MG content increased significantly. Moreover, the FPS
      treated group showed improvements in renal morphometry. In summary, FPS can
      ameliorate the metabolic abnormalities of diabetic rats and delay the progression
      of diabetic renal complications. 

PMID- 24886868
TI  - Identification of marine neuroactive molecules in behaviour-based screens in the
      larval zebrafish.
AB  - High-throughput behavior-based screen in zebrafish is a powerful approach for the
      discovery of novel neuroactive small molecules for treatment of nervous system
      diseases such as epilepsy. To identify neuroactive small molecules, we first
      screened 36 compounds (1-36) derived from marine natural products xyloketals and
      marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1
      demonstrated the most potent inhibition on the locomotor activity in larval
      zebrafish. Compounds 37-42 were further synthesized and their potential anti
      epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish.
      Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced
      locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound
      40 showed the most potent inhibitory action against PTZ-induced hyperactivity.
      The structure-activity analysis showed that the OH group at 12-position played a
      critical role and the substituents at the 13-position were well tolerated in the
      inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide
      some novel drug candidates for the treatment of epilepsy. 

PMID- 24886865
TI  - Quorum quenching agents: resources for antivirulence therapy.
AB  - The continuing emergence of antibiotic-resistant pathogens is a concern to human
      health and highlights the urgent need for the development of alternative
      therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial
      pathogens, and thus, is a promising target for antivirulence therapy which may
      inhibit virulence instead of cell growth and division. This means that there is
      little selective pressure for the evolution of resistance. Many natural quorum
      quenching (QQ) agents have been identified. Moreover, it has been shown that many
      microorganisms are capable of producing small molecular QS inhibitors and/or
      macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to
      gain benefits in competitive environments. More than 30 species of marine QQ
      bacteria have been identified thus far, but only a few of them have been
      intensively studied. Recent studies indicate that an enormous number of QQ
      microorganisms are undiscovered in the highly diverse marine environments, and
      these marine microorganism-derived QQ agents may be valuable resources for
      antivirulence therapy. 

PMID- 24886869
TI  - An online quality assurance program for colposcopy in a population-based cervical
      screening setting in Italy: results on colposcopic impression.
AB  - OBJECTIVE: To report the results of an Internet-based colposcopy quality
      assurance program from a population-based cervical screening service in a large
      region of northern Italy. METHODS: In 2010 to 2011, a Web application was made
      accessible on the Web site of the regional administration. Fifty-nine
      colposcopists of the registered 65 participated. They logged-in, viewed a posted
      set of 50 high-quality digital colpophotographs selected by an expert committee,
      and rated them for colposcopic impression using a 4-tier classification
      (Negative; abnormal, grade 1 [G1]; abnormal, grade 2 [G2]; suspected invasive
      cancer [Cancer]) derived from the International Federation for Cervical Pathology
      and Colposcopy 2002 classification. kappa (kappa) coefficients for
      intercolposcopist agreement and colposcopist-committee agreement were calculated.
      RESULTS: Colposcopist-committee agreement was greater than intercolposcopist
      agreement (overall kappa 0.69 vs 0.60, p<.001). The kappa values for colposcopist
      committee agreement were 0.83 on Negative, 0.53 on G1, 0.66 on G2, and 0.80 on
      Cancer (all p values for pairwise comparisons<.001, except for Negative vs Cancer
      [p=.078]). There was no systematic tendency for colposcopists to underestimate or
      overestimate the colposcopic findings (2-tailed sign test, p=.13). Overall
      colposcopist-committee agreement was greater among patients 35 years or older
      (p<.001) and for colposcopists with previous quality assurance experiences
      (p<.01). Only 0.2% of Negative impressions were formulated for a cervical
      intraepithelial neoplasia grade 2 or worse. As a parallel finding, the impression
      of Cancer predicted cervical intraepithelial neoplasia grade 2 or less in 0.5% of
      cases. The histologic substrates of G1 were dispersed over a large spectrum.
      CONCLUSIONS: The reproducibility of colposcopic impression, when classified by
      trained colposcopists examining high-quality images, is higher than is generally
      thought.

PMID- 24886870
TI  - Pagetoid spread of bladder urothelial carcinoma to the vagina and vulva.
AB  - OBJECTIVE: To study the clinicopathologic features of a rare disease of pagetoid
      urothelial intraepithelial neoplasia (PUIN) in the vulva. MATERIALS AND METHODS:
      We reviewed a case of PUIN in a Chinese woman with a long history of bladder
      urothelial carcinoma. RESULTS: The patient presented with vulvar pruritus for
      more than 1 month. Gynecologic examination showed a red, thickened, eczematoid
      lesion in the bilateral labia minora and a palpable 4-cm mass between the middle
      part of the vagina and the urethral meatus. Microscopically, the neoplastic cells
      with clear or pale eosinophilic cytoplasm were distributed throughout the
      squamous epithelium, with a predilection for the middle and basal portion in the
      vulva. Acantholysis-related papillary formation and pagetoid spread pattern to
      the normal squamous epithelium were also present. Invasive carcinoma was found
      underneath the unremarkable squamous epithelium in the vaginal biopsy.
      Immunohistochemistry demonstrated that these cells were negative for mucin stain,
      carcinoembryonic antigen, and 34betaE12 and were strongly positive for
      cytokeratins 5/6, 7, 18, 19, and 20. CONCLUSIONS: This rare entity of PUIN was
      associated with metastatic urothelial carcinoma and should be discriminated from
      vulvar Paget disease and pagetoid squamous cell carcinoma in situ.

PMID- 24886872
TI  - Primary vulvar lymphangioma circumscriptum: a case report and review of
      literature.
AB  - OBJECTIVE: To add a new case of primary vulvar lymphangioma circumscriptum to the
      literature and to review the current literature. MATERIALS AND METHODS: We
      searched the PubMed/MEDLINE databases for previous case reports using the key
      words "vulvar lymphangioma circumscriptum" and "primary vulvar lymphangioma
      circumscriptum." RESULTS: We found 21 cases of primary vulvar lymphangioma
      circumscriptum reported until 2013. Mean age was 32 years (range = 3-76 y), and
      62 % of the cases had been treated surgically. CONCLUSIONS: The treatment of
      primary vulvar lymphangioma circumscriptum is mainly surgery. Depending on the
      age of the patient and the extent of lesion, surgical treatment might be in the
      form of the local excision, labiectomy, or vulvectomy.

PMID- 24886871
TI  - Comparison of depth of necrosis using cryotherapy by gas and number of freeze
      cycles.
AB  - OBJECTIVE: This study aimed to establish the noninferiority of a single-freeze
      application with CO2 or N2O compared with the standard double freeze with N2O for
      cryotherapy treatment. MATERIALS AND METHODS: Sixty women undergoing hysterectomy
      for reasons other than cervical cancer or precancer were randomized to 1 of 3
      techniques as follows: (1) double freeze with N2O, (2) single freeze with N2O, or
      (3) single freeze with CO2. The cervix was separated and cut into anterior and
      posterior segments, and the deepest area of necrosis was recorded. Comparisons
      were made using regression analysis. The margin of noninferiority was defined as
      0.8 mm. RESULTS: On the anterior lip, a single freeze with N2O was noninferior to
      a double freeze of the same gas, but on the posterior lip, the single freeze was
      not. The single freeze of CO2 did not provide sufficient depth of necrosis in
      either lip to infer noninferiority versus the double freeze with N2O.
      CONCLUSIONS: A single freeze with N2O is noninferior to a double-freeze technique
      in the anterior but not the posterior lip. However, the result for posterior lips
      was close to reaching statistical significance. In addition, CO2 had
      approximately 1 mm shallower depth of necrosis compared with N2O techniques;
      however, the clinical implications are unknown. Given the extensive use of CO2
      globally, further clinical evaluation is needed.

PMID- 24886874
TI  - De novo SOX11 mutations cause Coffin-Siris syndrome.
AB  - Coffin-Siris syndrome (CSS) is a congenital disorder characterized by growth
      deficiency, intellectual disability, microcephaly, characteristic facial features
      and hypoplastic nails of the fifth fingers and/or toes. We previously identified
      mutations in five genes encoding subunits of the BAF complex, in 55% of CSS
      patients. Here we perform whole-exome sequencing in additional CSS patients,
      identifying de novo SOX11 mutations in two patients with a mild CSS phenotype.
      sox11a/b knockdown in zebrafish causes brain abnormalities, potentially
      explaining the brain phenotype of CSS. SOX11 is the downstream transcriptional
      factor of the PAX6-BAF complex, highlighting the importance of the BAF complex
      and SOX11 transcriptional network in brain development. 

PMID- 24886875
TI  - Inflammation biomarkers and delirium in critically ill patients.
AB  - INTRODUCTION: Delirium is a common occurrence in critically ill patients and is
      associated with an increase in morbidity and mortality. Septic patients with
      delirium may differ from a general critically ill population. The aim of this
      investigation was to study the relationship between systemic inflammation and the
      development of delirium in septic and non-septic critically ill patients.
      METHODS: We performed a prospective cohort study in a 20-bed mixed intensive care
      unit (ICU) including 78 (delirium = 31; non-delirium = 47) consecutive patients
      admitted for more than 24 hours. At enrollment, patients were allocated to septic
      or non-septic groups according to internationally agreed criteria. Delirium was
      diagnosed using the Confusion Assessment Method for the Intensive Care Unit (CAM
      ICU) during the first 72 hours of ICU admission. Blood samples were collected
      within 12 hours of enrollment for determination of tumor necrosis factor (TNF)
      alpha, soluble TNF Receptor (STNFR)-1 and -2, interleukin (IL)-1beta, IL-6, IL-10
      and adiponectin. RESULTS: Out of all analyzed biomarkers, only STNFR1 (P =
      0.003), STNFR2 (P = 0.005), adiponectin (P = 0.005) and IL-1beta (P < 0.001)
      levels were higher in delirium patients. Adjusting for sepsis and sedation, these
      biomarkers were also independently associated with delirium occurrence. However,
      none of them were significant influenced by sepsis. CONCLUSIONS: STNFR1, STNFR2,
      adiponectin and IL-1beta were associated with delirium. Sepsis did not modify the
      relationship between the biomarkers and delirium occurrence.

PMID- 24886876
TI  - Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid
      leukemias and affect microRNA binding.
AB  - BACKGROUND: MicroRNA dysregulation is a common event in leukemia. Polymorphisms
      in microRNA-binding sites (miRSNPs) in target genes may alter the strength of
      microRNA interaction with target transcripts thereby affecting protein levels. In
      this study we aimed at identifying miRSNPs associated with leukemia risk and
      assessing impact of these miRSNPs on miRNA binding to target transcripts.
      METHODS: We analyzed with specialized algorithms the 3' untranslated regions of
      137 leukemia-associated genes and identified 111 putative miRSNPs, of which 10
      were chosen for further investigation. We genotyped patients with acute myeloid
      leukemia (AML, n = 87), chronic myeloid leukemia (CML, n = 140), childhood acute
      lymphoblastic leukemia (ALL, n = 101) and healthy controls (n = 471). Association
      between SNPs and leukemia risk was calculated by estimating odds ratios in the
      multivariate logistic regression analysis. For miRSNPs that were associated with
      leukemia risk we performed luciferase reporter assays to examine whether they
      influence miRNA binding. RESULTS: Here we show that variant alleles of
      TLX1_rs2742038 and ETV6_rs1573613 were associated with increased risk of
      childhood ALL (OR (95% CI) = 3.97 (1.43-11.02) and 1.9 (1.16-3.11),
      respectively), while PML_rs9479 was associated with decreased ALL risk (OR = 0.55
      (0.36-0.86). In adult myeloid leukemias we found significant associations between
      the variant allele of PML_rs9479 and decreased AML risk (OR = 0.61 (0.38-0.97),
      and between variant alleles of IRF8_ rs10514611 and ARHGAP26_rs187729 and
      increased CML risk (OR = 2.4 (1.12-5.15) and 1.63 (1.07-2.47), respectively).
      Moreover, we observed a significant trend for an increasing ALL and CML risk with
      the growing number of risk genotypes with OR = 13.91 (4.38-44.11) for carriers of
      >=3 risk genotypes in ALL and OR = 4.9 (1.27-18.85) for carriers of 2 risk
      genotypes in CML. Luciferase reporter assays revealed that the C allele of
      ARHGAP26_rs187729 creates an illegitimate binding site for miR-18a-3p, while the
      A allele of PML_rs9479 enhances binding of miR-510-5p and the C allele of
      ETV6_rs1573613 weakens binding of miR-34c-5p and miR-449b-5p. CONCLUSIONS: Our
      study implicates that microRNA-binding site polymorphisms modulate leukemia risk
      by interfering with the miRNA-mediated regulation. Our findings underscore the
      significance of variability in 3' untranslated regions in leukemia.

PMID- 24886877
TI  - Prostaglandin E2 excitatory effects on guinea pig urinary bladder smooth muscle:
      a novel regulatory mechanism mediated by large-conductance voltage- and Ca2+
      activated K+ channels.
AB  - Prostaglandin E2 (PGE2) is an essential signaling molecule involved in the
      regulation of detrusor smooth muscle (DSM) function. However, the underlying
      regulatory mechanism by which PGE2 augments DSM cell excitability and
      contractility is not well understood. Here, we investigated whether PGE2 inhibits
      the large conductance voltage- and Ca(2+)-activated K(+) (BK) channels in guinea
      pig DSM, thereby increasing DSM excitability and contractility. We used a
      multidisciplinary experimental approach including amphotericin-B perforated patch
      clamp electrophysiology and live-cell Ca(2+) imaging in native freshly-isolated
      DSM cells, isometric tension recordings of intact DSM strips, and pharmacological
      tools to investigate BK channel regulation by PGE2 in guinea pig DSM. PGE2
      increased the spontaneous phasic contractions of isolated DSM strips in a
      concentration-dependent manner (10 nM-10 uM). BK channel inhibition with
      paxilline (1 uM) attenuated the PGE2-induced DSM phasic contractions, suggesting
      that BK channels are involved in the mechanism of PGE2-induced DSM contractions.
      PGE2 (10 uM) increased the intracellular Ca(2+) levels in freshly-isolated DSM
      cells. PGE2 (10 uM) also caused an inhibition of the amplitude and frequency of
      spontaneous transient BK currents in DSM cells. Moreover, PGE2 (10 uM) did not
      affect the amplitude of whole cell steady-state BK currents in DSM cells. Our
      findings provide strong experimental evidence that PGE2 leads to an inhibition of
      the spontaneous transient BK currents, elevation of intracellular Ca(2+) levels
      in freshly-isolated DSM cells, and augmentation of DSM phasic contractions. Thus,
      we have revealed a novel mechanism that BK channels mediate PGE2-induced
      contractions in guinea pig DSM.

PMID- 24886878
TI  - Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory
      depression in rats.
AB  - Reversing the respiratory depression induced by carfentanil involves intravenous
      administration of naloxone or naltrexone, but this treatment has disadvantages.
      Hence, finding a more appropriate treatment to counter the depressive actions of
      carfentanil is needed. In the present study, with the naloxone as a control, we
      investigated the efficacy of nalmefene for countering the depressive actions of
      carfentanil. Rats were treated successively with carfentanil (10 MUg/kg, i.v.)
      and nalmefene (9.4-150.0 MUg/kg, i.m.), and the duration of loss of righting
      reflex (LORR) recorded. Respiratory parameters were measured in free-moving rats
      using a whole-body plethysmograph after rats were administered carfentanil (20
      MUg/kg, i.v.) and nalmefene (9.4-150.0 MUg/kg, i.m.) sequentially. The parameters
      of arterial blood gases were also examined. Nalmefene (9.4-150.0 MUg/kg, i.m.)
      treatment dose-dependently decreased the duration of carfentanil-induced LORR.
      The respiratory rate after 60 min of nalmefene (150.0 MUg/kg, i.m.) treatment
      increased from 34.3 +/- 5.3 bursts/min to 117.8 +/- 18.9 bursts/min, and enhanced
      pause decreased from 1.1 +/- 0.1 to 0.4 +/- 0.1, and was close to those of normal
      rats. Furthermore, nalmefene (37.5-150.0 MUg/kg) treatment could enable the PaO2,
      SaO2 and PaCO2 to approach normal levels 10 min (15 min after carfentanil
      injection) or 30 min (25 min after carfentanil injection) after injection. While,
      a single injection of naloxone (150.0 MUg/kg, i.m.) only achieved partial
      remission of respiratory depression. These data suggest that nalmefene more
      effectively counters the depressive actions induced by carfentanil and is a more
      appropriate treatment to antagonize carfentanil toxicity compared with naloxone.

PMID- 24886879
TI  - The influence of smooth muscle content and orientation in dissected human
      pregnant myometrial strips on contractility measurements.
AB  - This study examined the hypothesis that the force generated by myometrial strips
      from pregnant women is influenced by the smooth muscle content and fibre
      orientation of the strips and that correcting for these structural variables will
      provide a more accurate measure of contractility. Myometrial strips (n=72) were
      contracted by exposure to KCl, oxytocin, U44619 and phenylephrine and maximum
      responses were recorded. Morphological techniques were used to determine the
      cross-sectional area of the strips, the area occupied by smooth muscle and the
      area occupied by smooth muscle longitudinal in the strip. Maximum responses to
      contractile agents were expressed in terms of these three variables. The mean
      cross sectional area of strips was 2.01 +/- 0.06 mm(2), of which 50% was smooth
      muscle, and 18% was smooth muscle longitudinal in the strip (n=72). There was
      much heterogeneity in responses, smooth muscle content and fibre orientation.
      Correction for morphological variability did not improve the heterogeneity in
      responses where coefficients of variation among strips from the same donor ranged
      from 43% to 63% when expressed in relation to longitudinal smooth muscle cross
      sectional area. The standard method of preparation of myometrial strips for in
      vitro recording results in samples that are not structurally uniform. Correcting
      for the known structural variables does not provide a more accurate measure of
      maximum contractile responses. Because of the heterogeneity shown here,
      experiments that are dependent upon accurate estimation of maximum contractile
      responses require a large number of replicates to reach meaningful conclusions.

PMID- 24886880
TI  - Influence of acute treatment with sibutramine on the sympathetic
      neurotransmission of the young rat vas deferens.
AB  - The effects of acute treatment with sibutramine on the peripheral sympathetic
      neurotransmission in vas deferens of young rats were still not evaluated.
      Therefore, we carried out this study in order to verify the effects of acute
      sibutramine treatment on the neuronal- and exogenous agonist-induced contractions
      of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated
      with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment.
      The acute treatment with sibutramine was able to increase the potency (pD2) of
      noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline
      was increased while the efficacy of serotonin and nicotine were decreased. The
      maximum effect induced by a single concentration of tyramine was diminished in
      the vas deferens from treated group. Moreover, the leftward shift of the
      noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and
      beta-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of
      treated group. The initial phasic and secondary tonic components of the neuronal
      evoked contractions of vas deferens from treated group at the frequencies of 2 Hz
      were decreased. Moreover, only the initial phasic component at 5 Hz was
      diminished by the acute treatment with sibutramine. In conclusion, we showed that
      the acute treatment with sibutramine in young rats was able to affect the
      peripheral sympathetic nervous system by inhibition of noradrenaline uptake and
      reduction of the neuronal content of this neurotransmitter, leading to an
      enhancement of vas deferens sensitivity to noradrenaline.

PMID- 24886881
TI  - Artemisinin protects against dextran sulfate-sodium-induced inflammatory bowel
      disease, which is associated with activation of the pregnane X receptor.
AB  - Artemisinin has been used to treat malaria for centuries in the context of
      traditional Chinese medicine. In the present study, the effects of artemisinin on
      pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in
      inflammatory bowel disease were investigated. LS174T cells exposed to artemisinin
      at various concentrations and for different periods of time were examined with
      respect to the specific induction of CYP3A4 and PXR mRNA expression. Transient
      transfection experiments showed transcriptional activation of the CYP3A4 gene
      through artemisinin to be PXR-dependent. An electrophoretic-mobility shift assay
      (EMSA) showed that artemisinin activates the DNA-binding capacity of the PXR for
      the CYP3A4 element. These results indicate that the induction of CYP3A4 by
      artemisinin is mediated through the activation of PXR. Using animal models, it
      was demonstrated that artemisinin abrogates dextran sulfate sodium (DDS)-induced
      intestinal inflammation. Preadministration of artemisinin ameliorated the
      clinical hallmarks of colitis in DSS-treated mice as determined by body weight
      loss and assessment of diarrhea, rectal bleeding, colon length, and histology.
      Artemisinin was found to prevent or reduce the severity of colonic inflammation
      by inducing CYP3A expression by activation of PXR. 

PMID- 24886882
TI  - Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates
      behavioral disorders of the dementia mouse model induced by Abeta 1-42.
AB  - Semen Ziziphi Spinosae (SZS) has been used as a hypnotic-sedative medicine for
      thousands of years. Recently, SZS has also shown notable neuroprotective
      activities via anti-oxidative and anti-inflammatory effects in dementia animals.
      Jujuboside A (JuA), isolated from SZS, has been proved to be a major hypnotic
      sedative component of SZS. In the present study, we firstly evaluated the effects
      of intracerebroventricular (ICV) injection of JuA (0.02 and 0.2mg/kg) for five
      consecutive days on cognitive impairment induced by ICV injection of Abeta 1-42.
      The results showed that ICV treatment with JuA significantly mitigated learning
      and memory impairment in mice induced by Abeta 1-42 as measured by the Y-maze,
      active avoidance and Morris water maze. Furthermore, ICV treatment with JuA
      reduced the level of Abeta 1-42 in hippocampus, significantly inhibited the
      activities of acetylcholinesterase (AChE) and NO, and decreased the amount of the
      increased malondialdehyde (MDA) in the hippocampus and cerebral cortex of mice
      treated with ICV injection of Abeta 1-42. Shrinkage of nuclei, swollen and
      eccentrically dispersed neuronal bodies were observed in hippocampus of AD mice
      induced by Abeta 1-42, however, JuA noticeably improved the histopathological
      damage. Cumulatively, the present study indicates that JuA may serve as a
      potential therapeutic agent for the treatment of Alzheimer' disease.

PMID- 24886883
TI  - Inhibition of native 5-HT3 receptor-evoked contractions in guinea pig and mouse
      ileum by antimalarial drugs.
AB  - Quinine, chloroquine and mefloquine are commonly used to treat malaria, however,
      with associated gastrointestinal (GI) side-effects. These drugs act as
      antagonists at recombinant 5-HT3 receptors and modulate gut peristalsis. These
      gastrointestinal side effects may be the result of antagonism at intestinal 5-HT3
      receptors. Ileum from male C57BL/6 mice and guinea pigs was mounted
      longitudinally in organ baths. The concentration-response curves for 5-HT and the
      selective 5-HT3 agonist 2-Me-5-HT were obtained with 5-HT (pEC50 = 7.57 +/- 0.33,
      12) more potent (P = 0.004) than 2-Me-5-HT (pEC50 = 5.45 +/- 0.58, n = 5) in
      mouse ileum. There was no difference in potency of 5-HT (pEC50 = 5.42 +/- 0.15, n
      = 8) and 2-Me-5-HT (pIC50 = 5.01 +/- 0.55, n = 11) in guinea pig ileum (P >
      0.05). Quinine, chloroquine or mefloquine was applied for 10 min and inhibitions
      prior to submaximal agonist application. In mouse ileum, quinine, chloroquine and
      mefloquine antagonised 5-HT-induced contractions (pIC50 = 4.9 +/- 0.17, n = 7;
      4.76 +/- 0.14, n = 5; 6.21 +/- 0.2, n = 4, correspondingly) with mefloquine most
      potent (P < 0.05). Quinine, chloroquine and mefloquine antagonised 2-me-5-HT
      induced contractions (pIC50 = 6.35 +/- 0.11, n = 8; 4.64 +/- 0.2, n = 7; 5.11 +/-
      0.22, n = 6, correspondingly) with quinine most potent (P < 0.05). In guinea-pig
      ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions
      (pIC50 = 5.02 +/- 0.15, n = 6; 4.54 +/- 0.1, n = 7; 5.32 +/- 0.13, n = 5) and 2
      me-5-HT-induced contractions (pIC50 = 4.62 +/- 0.25, n = 5; 4.56 +/- 0.14, n = 6;
      5.67 +/- 0.12, n = 4) with chloroquine least potent against 5-HT and mefloquine
      most potent against 2-me-5-HT (P < 0.05). These results support previous studies
      identifying anti-malarial drugs as antagonists at recombinant 5-HT3 receptors and
      may also demonstrate the ability of these drugs to influence native 5-HT3
      receptor-evoked contractile responses which may account for their associated GI
      side-effects.

PMID- 24886884
TI  - L-type Ca2+ channel blockers inhibit the window contraction of mouse aorta
      segments with high affinity.
AB  - L-type calcium channel blockers (LCCBs) reduce blood pressure more effectively in
      hypertensive than in normotensive subjects and are more effective in vascular
      smooth muscle (VSM) than in cardiac muscle. This has been explained by the
      depolarized resting potential of VSM in comparison with heart muscle cells and
      during hypertension, because both favor the "high affinity" inactivated state of
      the L-type calcium channel (LCC). Depolarized resting potentials, however, also
      increase Ca(2+) influx via window, non-inactivating LCC. The present study
      investigated whether these channels can be effectively blocked by nifedipine,
      verapamil or diltiazem, as representatives of different LCCB classes. C57Bl6
      mouse aortic segments were depolarized by 50mM K(+) to attain similar degree of
      inactivation. The depolarization evoked biphasic contractions with the slow force
      component displaying higher sensitivity to LCCBs than the fast component. Removal
      of the fast force component increased, whereas stimulation of Ca(2+) influx with
      the dihydropyridine BAY K8644, a structural analog of nifedipine, decreased the
      efficacy of the LCCBs. Addition of LCCBs during the contraction caused
      concentration-dependent relaxation, which was independent of the presence of a
      fast force component, but still showed lower sensitivity in the presence of BAY
      K8644. Our data suggest that steady-state contractions by depolarization with
      50mM K(+) are completely due to window Ca(2+) influx, which is preferentially
      inhibited by LCCBs. Furthermore, results point to interactions between the LCCB
      receptors and Ca(2+) ions or BAY K8644. The high affinity for open, non
      inactivating LCC may play a dominant role in the anti-hypertensive effects of
      LCCBs.

PMID- 24886885
TI  - The effect of bradykinin on the electrical activity of rat myenteric neurons.
AB  - Bradykinin is a mediator involved in inflammatory processes in the gut. Here we
      investigated the effect of bradykinin on the electrical activity of rat myenteric
      neurons, the key players for regulation of gastrointestinal motility. Bradykinin
      (2 * 10(-8)mol/l) induced a biphasic increase in frequency of action potentials
      measured with microelectrode arrays. This increase was mirrored by a biphasic
      increase in cytosolic Ca(2+) concentration ([Ca(2+)]i), which was observed in
      about 40% of the myenteric neurons. The bradykinin B1 receptor agonist des-arg(9)
      bradykinin as well as the bradykinin B2 receptor agonist hyp(3)-bradykinin
      induced a similar effect on [Ca(2+)]i. Immunocytochemical stainings confirmed the
      expression of both receptor types by myenteric ganglionic cells. Real time PCR
      showed that the inducible B1 receptor was upregulated during cell culture. The
      inhibition of cyclooxygenases with piroxicam reduced the effect of bradykinin on
      the electrical activity of myenteric neurons. The suppression of the glial growth
      on microelectrode arrays did not affect the bradykinin-induced change in
      frequency of action potentials. This suggests that prostaglandins, which probably
      mediate the effect of bradykinin, are not exclusively released from glial cells.
      The bradykinin-induced increase in [Ca(2+)]i was dependent on the presence of
      extracellular Ca(2+) and was inhibited by Co(2+), Cd(2+), and Ni(2+), blockers of
      voltage-dependent Ca(2+) channels, indicating a stimulation of the influx of
      extracellular Ca(2+) by the kinin. Consequently, bradykinin induces a Ca(2+)
      influx in myenteric neurons via Ca(2+) channels in the plasma membrane.

PMID- 24886886
TI  - Baclofen and 2-hydroxysaclofen modify acute hypolocomotive and antinociceptive
      effects of nicotine.
AB  - The aim of the present study was to evaluate the possible involvement of GABAB
      receptors in nicotine-induced hypolocomotion and antinociceptive effects in mice.
      Animals were exposed to nicotine only once. Acute nicotine hydrogen tartrate salt
      (3mg/kg; subcutaneous, s.c.) administration induced hypolocomotion and
      antinociceptive responses in the tail-immersion and the hot-plate tests. The
      effects of pretreatment with either the GABAB receptor agonist baclofen (1, 2 and
      3mg/kg; intraperitoneal, i.p.) or GABAB receptor antagonist 2-hydroxysaclofen
      (0.25, 0.5 and 1mg/kg; i.p.) were evaluated on these behavioral nicotine
      responses. The GABAB receptor agonist, baclofen (3mg/kg, i.p.) abolished nicotine
      induced antinociceptive effects in the tail-immersion and the hot-plate tests,
      but did not modify nicotine-induced hypolocomotion. In addition, the GABAB
      receptor antagonist, 2-hydroxysaclofen (1mg/kg, i.p.) increased nicotine-induced
      antinociceptive effects in the tail-immersion and the hot-plate tests, and
      abolished nicotine-induced hypolocomotion. The present results shed light that
      the GABAB receptor has an important role in mediating specific acute nicotine
      responses such as hypolocomotion and antinociception in mice. 

PMID- 24886888
TI  - Extracellular signal-regulated kinase, receptor interacting protein, and reactive
      oxygen species regulate shikonin-induced autophagy in human hepatocellular
      carcinoma.
AB  - Shikonin, a naphthoquinone derived from the Chinese medicinal plant Lithospermum
      erythrorhizon, shows potential to be a cancer chemotherapeutic agent. Our
      previous data demonstrate that high doses (about 6 MUM) of shikonin induce
      apoptosis in human hepatocellular carcinoma (HCC) cells. Here, we discovered that
      a low dose of shikonin (2.5 MUM) and a short treatment time (12h) induced
      autophagy, as evidenced by the upregulation of microtubule-associated protein
      1A/1B-light chain 3 (LC3)-II, the formation of acidic autophagic vacuoles (AVOs),
      and the punctate fluorescence pattern of GFP-LC3 protein. Next, we investigated
      the mechanism and found reactive oxygen species accumulation after shikonin
      treatment. The reactive oxygen species scavengers NAC and Tiron completely
      blocked autophagy. We further found activation of ERK by generation of reactive
      oxygen species and inhibition of RIP pathway, which are at least partially
      connected to shikonin-induced autophagy. Moreover, experiments in vivo revealed
      similar results: shikonin caused the accumulation of reactive oxygen species and
      phospho-ERK and thus induced autophagy in a tumor xenograft model. These findings
      suggest that shikonin is an inducer of autophagy and may be a promising clinical
      antitumor drug.

PMID- 24886887
TI  - Phenylephrine activates eNOS Ser 1177 phosphorylation and nitric oxide signaling
      in renal hypertensive rat aorta.
AB  - The endothelial nitric oxide synthase (eNOS) plays an important role in the
      control of the vascular tone. This work aimed to evaluate the role of an alpha1
      adrenoceptor agonist phenylephrine (PE) on eNOS activity and downstream signaling
      pathway activation in normotensive (2K) and renal hypertensive (2K-1C) intact
      endothelium rat aortas. Concentration-effect curves were performed for PE in
      intact-endothelium aortas from 2K and 2K-1C rats, in the absence of or in the
      presence of NOS or soluble guanylyl cyclase (sGC) inhibitor. Intact endothelium
      aortas were stimulated with PE in organ chambers and eNOS Ser(1177)/Thr(495)
      phosphorylation expression was evaluated by western blot. Nitric Oxide (NO)
      production was evaluated in isolated endothelial cells from 2K and 2K-1C rat
      aortas by flow-cytometry using NO selective fluorescent probe, DAF-2DA. The sGC
      activity/expression was also evaluated. PE-induced contractile response is lower
      in 2K-1C than in 2K intact-endothelium rat aorta. This is due to higher eNOS
      Ser(1177) phosphorylation in 2K-1C, which induces the eNOS overactivation. It was
      abolished by NOS or sGC inhibition. Phenylephrine reduces NO production in 2K as
      compared to the basal level, but it is not modified in 2K-1C. In PE-stimulated
      endothelial cells, the NO production is higher in 2K-1C than in 2K. Phenylephrine
      induces higher cGMP production in 2K-1C than in 2K, despite the lower expression
      of sGC in 2K-1C. Our results suggest that alpha1-adrenoceptor activation
      contributes to the increased activity of the enzyme eNOS by Ser(1177)
      phosphorylation in 2K-1C intact-endothelium aorta, which consequently decreases
      PE-induced contractile response. 

PMID- 24886890
TI  - [Epidemiology and anatomy of head and neck cancers].
AB  - Oral cavity and pharyngeal cancers account for 75% of head and neck cancers and
      are the fourth most spread cancer in men. Their incidence has decreased since
      1980 in men (incidence from 2011 gives 13,930 for lip, oral cavity, pharyngeal
      and laryngeal carcinomas) but has increased in women, linked to the more recent
      smoking or alcohol intoxication in women. In addition to the smoking or alcohol
      consumption risk factors, the EBV role in nasopharyngeal carcinomas, HPV in the
      oropharyngeal carcinomas and professional exposures in paranasal sinuses cancers
      are recognized. Head and neck cancers are the fifth most common cancer in men
      mortality in France. Extended anatomical sites reflect the diagnostic's
      complexity specific to some locations (sinuses, nasopharynx), possible therapies
      and prognosis depending on the affected site. 

PMID- 24886891
TI  - [Rare tumors of the head and neck; on behalf of the REFCOR, the French Network of
      rare head and neck tumors].
AB  - Malignant tumors of the upper aerodigestive tract may be rare by their histology
      (sarcoma, variants of conventional squamous cell carcinomas) and/or location
      (sinuses, salivary glands, ear, of various histologies themselves). They
      represent less than 10% of head and neck neoplasms. The confirmation of their
      diagnosis often requires a medical expertise and sometimes biomolecular
      techniques complementary to classical histology and immunohistochemistry. Due to
      their location, their treatment often requires a specific surgical technique.
      Radiation therapy is indicated based on histoclinical characteristics common to
      other head and neck neoplasms but also incorporate grade. Further, the technique
      must often be adapted to take into account the proximity of organs at risk. For
      most histologies, chemotherapy is relatively inefficient but current molecular
      advances may allow to consider pharmaceutical developments in the coming years.
      The REFCOR, the French Network of head and neck cancers aims to organize and
      promote the optimal management of these rare and heterogeneous diseases, to
      promote research and clinical trials. 

PMID- 24886892
TI  - [Oral cavity cancer, an update on behalf of Intergroupe ORL].
AB  - Oral cavity cancers are frequent: 6,600 cases per year are diagnosed in France.
      Age of occurrence is around 60. Tobacco is the main risk factor, especially when
      associated with alcohol. They occur de novo or by evolution of a precancerous
      lesion. Diagnosis is late in 70% of cases. They must be treated in specialized
      centers. Pretreatment check-up has to be done according to national guidelines.
      Treatment often implies primary surgery. Reconstructive surgery progresses allow
      for wide excisions and still acceptable quality of life. Radiotherapy, eventually
      potentialized, is usually performed post-operatively. Induction chemotherapy
      still needs to be evaluated in oral cancers, especially in an organ preservation
      purpose.

PMID- 24886889
TI  - Programmed DNA elimination in multicellular organisms.
AB  - Genetic information typically remains constant in all cells throughout the life
      cycle of most organisms. However, there are exceptions where DNA elimination is
      an integral, developmental program for some organisms, associated with generating
      distinct germline versus somatic genomes. Programmed DNA elimination occurs in
      unicellular ciliates and diverse metazoa ranging from nematodes to vertebrates.
      DNA elimination can occur through chromosome breakage and selective loss of
      chromosome regions or the elimination of individual chromosomes. Recent studies
      provide compelling evidence that DNA elimination is a novel form of gene
      silencing, dosage compensation, and sex determination. Further identification of
      the eliminated sequences, genome changes, and in depth characterization of this
      phenomenon in diverse metazoans is needed to shed new light on the functions and
      mechanisms of this regulated process. 

PMID- 24886893
TI  - [Oropharyngeal cancer].
AB  - Oropharyngeal carcinomas, contrary to other head and neck carcinomas are of
      increasing frequency, mostly due to a frequent association with human
      papillomavirus infection. Pluridisciplinary management is necessary. New
      techniques as transoral surgery or intensity-modulated radiation therapy have the
      potential to reduce toxicities and morbidity while offering equivalent local
      control rates. Early stages may be treated with single modality treatment
      (surgery or radiotherapy) with five-year overall survival rate exceeding 80%.
      Advanced stages need therapeutic associations and five-years survival rates are
      inferior to 40%. 

PMID- 24886894
TI  - [Squamous cell carcinoma of the hypopharynx and larynx: evidence-based care].
AB  - Squamous cell carcinomas of larynx and hypopharynx can be treated by surgery
      and/or radiotherapy according to tumor size. For small tumors, the results are
      similar. For locally advanced tumors, the surgical approach is mutilating and
      requires a total (pharyngo)laryngectomy. Exclusive chemoradiotherapy has shown
      its interest at the cost of late sequelae. In order to reduce these effects and
      mutilation, induction chemotherapy with cisplatin, docetaxel and 5FU for organ
      preservation becomes the standard treatment but there are no solid studies
      comparing this approach with the exclusive chemoradiotherapy. And it is not
      possible to conclude as to the superiority of a scheme in terms of overall
      survival. When chemotherapy is chosen, the modalities of any potentiation of
      radiation have not been yet established. 

PMID- 24886895
TI  - [Nasopharyngeal cancers, an overview].
AB  - Cancer of the nasopharynx is an uncommon malignancy in France (incidence  = 
      0.5/year/100,000 men) but is endemic in areas like in South-East Asia. Exclusive
      radiation therapy used to be the standard and results in local control rates for
      T3-T4 tumors around 50-75 %. Intensity-modulated radiotherapy (IMRT) improves
      tumor coverage with a sparing of organs at risk and has to be privileged.
      Concurrent chemotherapy with IMRT achieved significant survival benefice with 5
      year overall survival above 75 %. Concurrent radiochemotherapy with platinum is
      the most frequent scheme but induction and adjuvant chemotherapies are discussed
      to reduce distant failure: studies are currently ongoing. Follow-up aims to
      detect early local failures with a chance of cure and to manage long-term
      toxicities.

PMID- 24886896
TI  - [Lymph node metastases from squamous cell carcinoma of unknown primary site. Is
      it time to change of paradigm?].
AB  - The diagnosis of carcinoma of unknown primary (CUP) is made after exclusion of
      the presence of a mucosal primary. There are two mains options for the primary
      treatment of CUP, either a neck node dissection followed by postoperative
      radiotherapy or chemo-radiotherapy, or a primary radiotherapy or chemo
      radiotherapy depending on the nodal stage followed in case of residual neck
      disease by a selective neck dissection. There is no data to suggest the
      superiority of one over the other. For radiotherapy, unilateral neck or bilateral
      neck, including the upper aerodigestive tract mucosa are possible options. There
      is no definite data to demonstrate the superiority of one over the other, but
      owing the reduced toxicity of unilateral irradiation, and the possibility of
      salvage treatment in case of emergence of a mucosal primary and/or a
      contralateral neck node development, the former may be the preferred option.
      Advances in radiotherapy such as intensity modulated radiation therapy have the
      potential to spare organs at risk and reduce late toxicity rates. A selective
      irradiation approach customized on "major" criteria, such as nodal stage and
      level, HPV and EBV status and accessory criteria, such as histological variants,
      is under investigation. 

PMID- 24886897
TI  - [Quality control in pathology and theranostics in head and neck cancers].
AB  - Head and neck malignant tumors diagnosis require both standardized technical and
      personalized management in order to optimize patient care and therapy. The
      quality of multidisciplinary discussion for that goal needs common vocabulary.
      More than morphology, immunohistochemistry and in situ hybridization, additional
      molecular theranostics approaches are in fast progress in head and neck cancers,
      as well as their other anatomic counterparts. 

PMID- 24886898
TI  - [Imaging in head and neck cancers].
AB  - The head and neck imaging plays a central role at all stages of the management of
      cancer. Indeed, the image allows the oncology planning, surgery and radiotherapy.
      It is a multimodal imaging and the advantages and limitations of each technique
      must be known. Good knowledge of cervical anatomy is a necessary prerequisite for
      communication with the multidisciplinary committee. The computerised
      tomodensitometry is the gold standard for the pharyngolarynx. The MRI is the
      modality of choice for the oral cavity, oropharynx and nasopharynx. Ultrasound
      allows a comprehensive study of cervical lymph nodes. Functional imaging and
      nuclear medicine are still under evaluation. However, the literature already
      allows establishing their usefulness where morphological imaging is limited. The
      diagnosis of subclinical metastatic lymph nodes, the differentiation between
      recurrence and post-treatment modifications, monitoring chemotherapy and
      radiation therapy planning are indications for which new imaging techniques are
      invaluable. 

PMID- 24886899
TI  - [Quality criteria in radiotherapy for head and neck cancers under the aegis of
      Head and Neck Intergroup].
AB  - The aim of radiotherapy is to deliver enough radiation to the tumor in order to
      achieve maximum tumour control in the irradiated volume with as few serious
      complications as possible with an irradiation dose as low as possible to normal
      tissue. The quality of radiotherapy is essential for optimal treatment and
      quality control is to reduce the bias in clinical trials avoiding possible major
      deviations. The assurance and quality control programs have been developed in
      large european (EORTC, GORTEC) and american cooperative groups (RTOG) of
      radiation oncology since the 1980s. We insist here on the importance of quality
      assurance in radiotherapy and the current status in this domain and the criteria
      for quality control especially for current clinical trials within GORTEC are
      discussed here. 

PMID- 24886900
TI  - [Quality assurance in head and neck medical oncology].
AB  - In medical oncology, how can we be sure that the right drug is being administered
      to the right patient at the right time? The implementation of quality assurance
      criteria is important in medical oncology, in order to ensure that the patient
      receives the best treatment safely. There is very little literature about quality
      assurance in medical oncology, as opposed to radiotherapy or cancer surgery.
      Quality assurance must cover the entire patient care process, from the diagnosis,
      to the therapeutic decision and drug distribution, including its selection, its
      preparation and its delivery to the patient (administration and dosage), and
      finally the potential side effects and their management. The dose-intensity
      respect is crucial, and its reduction can negatively affect overall survival
      rates, as shown in breast and testis cancers for example. In head and neck
      medical oncology, it is essential to respect the few well-standardized
      recommendations and the dose-intensity, in a population with numerous
      comorbidities. We will first review quality assurance criteria for the general
      medical oncology organization and then focus on head and neck medical oncology.
      We will then describe administration specificities of head and neck treatments
      (chemoradiation, radiation plus cetuximab, postoperative chemoradiation,
      induction and palliative chemotherapy) as well as their follow-up. Lastly, we
      will offer some recommendations to improve quality assurance in head and neck
      medical oncology. 

PMID- 24886901
TI  - [Quality assurance in head and neck surgical oncology].
AB  - In patients' management affected by head and neck cancers, surgery takes a major
      place with radiotherapy and chemotherapy. An updating of the surgical techniques
      available, and validated indications seems useful to harmonize the head and neck
      oncological surgery practices and so optimize its safety. A focus on the quality
      assurance in head and neck surgical oncology is proposed. 

PMID- 24886902
TI  - [Quality of life and supportive care in head and neck cancers].
AB  - The quality of life of patients treated for head and neck cancers and their
      carers is part of the current concerns of health care teams. Assessment tools
      were created and helped to highlight the severe physical effects (pain,
      mucositis...) and chronic (mutilation, post-radiation complications...) related
      to the disease or to different treatments but also to consider the psychosocial
      impact of this disease. Improving the quality of life through a thoughtful and
      comprehensive support that must be associated with somatic care, mental health
      care, rehabilitation and inclusion of social difficulties and suffering
      relatives. Supportive care shall ensure a good quality of life for patients
      treated and their families but also reduce the physical effects associated with
      the disease and treatment. They rely on coordination of care including the cancer
      networks established in the cancer plan to ensure comprehensive and continuous
      care for these patients.

PMID- 24886903
TI  - [Recurrence of upper aerodigestive tract tumors].
AB  - Recurrences of tumours of the upper aerodigestive tract are frequent despite the
      improvement of the primary treatment and they limit the rate of survival long
      term. They occur in patients with multiple co-morbidities, often associated with
      sequelae or side effects of earlier treatments. The salvage treatment will add a
      cumulative toxicity and therapeutic options are limited. The choice will go from
      curator to palliative treatment. The report benefit-risk must be assessed in each
      case depending on the terrain and prognostic factors that have been identified,
      such as performance status, the time between initial disease and the recurrence,
      the site and the stratification of the recurrence. In operable non-metastatic
      recurrence surgery remains the treatment of choice. Multimodal treatment
      involving surgery, radiation therapy and chemotherapy in this context is being
      evaluated. Non-operable tumors have long been considered only in a palliative
      context. The evaluation of detailed irradiation as bifractionnated radiotherapy
      combined with chemotherapy helped establish protocols allowing long-term
      survivals and consider these treatments as potentially curators. However, the
      toxicity of these treatments is important. That is why the technical innovations
      of the radiation and the development of new chemotherapeutic agents today offer
      opportunities remaining to assess. The use of irradiation targeted by intensity
      modulated radiation therapy (IMRT), and stereotactic radiotherapy by decreasing
      the irradiated volume should decrease the toxicity. Generally better tolerated
      than conventional chemotherapy agents, targeted therapies also took their places
      associated with radiotherapy in the treatment of these patients already treated.
      Cetuximab was the first agent obtaining an indication. Other agents are being
      evaluated in metastatic recurrent tumors, including exploring the possibilities
      of radiopotentialisation nanoparticles and the inhibitors of apoptosis proteins. 

PMID- 24886904
TI  - Genome-wide copy number variation study reveals KCNIP1 as a modulator of insulin
      secretion.
AB  - Copy number variations (CNVs) have emerged as another important genetic marker in
      addition to SNP for understanding etiology of complex diseases. In light of this,
      we performed a genome-wide CNV study to identify type 2 diabetes (T2D)-associated
      CNV using an array comparative genomic hybridization from 3180 subjects for T2D
      cases (n=863) and controls (n=2,317). Thus, five CNV regions having a p-value
      threshold <=0.05 were identified and evaluated by validation with quantitative
      PCR and comparison with previously reported CNV regions in the Database of
      Genomic Variants. Furthermore, we performed a functional experiment to assess the
      biological significance of a gene encompassing a CNV region. The inhibition of
      KCNIP1 led to increased insulin secretion in a glucose-dependent manner, but had
      no effect on insulin gene transcription as well as cell apoptosis. Taken
      together, these data indicate that KCNIP1 from CNV study might function as a T2D
      susceptibility gene whose dysregulation alters insulin production. 

PMID- 24886905
TI  - Immobilisation increases yeast cells' resistance to dehydration-rehydration
      treatment.
AB  - This study was performed with the goal of revealing if the dehydration procedure
      used in our new immobilisation method noticeably decreases the viability of yeast
      cells in immobilised preparations. Various yeasts were used in this research:
      Saccharomyces cerevisiae cells that were rather sensitive to dehydration and had
      been aerobically grown in an ethanol-containing medium, a recombinant strain of
      S. cerevisiae grown in aerobic conditions which were completely non-resistant to
      dehydration and an anaerobically grown bakers' yeast strain S. cerevisiae, as
      well as a fairly resistant Pichia pastoris strain. Experiments performed showed
      that immobilisation of all these strains essentially increased their resistance
      to a dehydration-rehydration treatment. The increase of cells' viability
      (compared with control cells dehydrated in similar conditions) was from 30 to
      60%. It is concluded that a new immobilisation method, which includes a
      dehydration stage, does not lead to an essential loss of yeast cell viability.
      Correspondingly, there is no risk of losing the biotechnological activities of
      immobilised preparations. The possibility of producing dry, active yeast
      preparations is shown, for those strains that are very sensitive to dehydration
      and which can be used in biotechnology in an immobilised form. Finally, the
      immobilisation approach can be used for the development of efficient methods for
      the storage of recombinant yeast strains. 

PMID- 24886906
TI  - Analysis of the cost-effectiveness of surfactant treatment (Curosurf(r)) in
      respiratory distress syndrome therapy in preterm infants: early treatment
      compared to late treatment.
AB  - BACKGROUND: The best criteria for surfactant treatment in the perinatal period
      are unknown and this makes it of interest to consider the possible economic
      implications of lessening the use of more restrictive criteria. OBJECTIVE: The
      objective of this study is the evaluation of the costs of respiratory care for
      preterm infants with Respiratory Distress Syndrome (RDS) treated with "early
      rescue" surfactant compared to a "late rescue" strategy. METHODS: The study was
      carried out applying the costs of materials used, of staff and pharmacological
      therapy calculated in the Neonatal Intensive Care Unit (NICU) of an Italian
      hospital to the Verder et al. study (Pediatrics 1999) clinical data. RESULTS: The
      cost for patients treated with early strategy was slightly lower than for
      patients treated with late strategy (Euro 4,901.70 vs. Euro 4,960.07). The cost
      of treatment with surfactant was greater in the early group (Euro 458.49 vs. Euro
      311.74), but this was compensated by the greater cost of treatment with
      Mechanical Ventilation (MV) in the late group (respectively Euro 108.85 vs. Euro
      259.25). CONCLUSIONS: The cost-effectiveness analysis performed in this study
      shows how early treatment with surfactant in preterm infants with RDS, as well as
      being clinically more effective, is associated with a slightly lower cost.

PMID- 24886909
TI  - Influencing and modifying children's energy intake: the role of portion size and
      energy density.
AB  - Childhood obesity is of concern worldwide. The portion size (PS) and energy
      density (ED) of food are two major determinants of children's energy intake (EI).
      Trends towards increasing PS are most apparent and best documented in the USA,
      where PS of numerous food products have increased in the marketplace over the
      past three decades, particularly high-energy dense foods. Analyses of population
      level dietary surveys have confirmed this trend in children for both in- and out
      of-home eating, and a plethora of observational evidence positively associates
      PS, ED and adiposity in children. A limited number of intervention studies
      provide clear evidence that children, even as young as 2 years, respond acutely
      to increasing PS, with some studies also demonstrating the additive effects of
      increased ED in promoting excessive EI. However, most of the evidence is based on
      children aged 3-6 years and there is a paucity of data in older children and
      adolescents. It is unclear whether decreasing PS can have the opposite effect on
      children's EI but recent acute studies have demonstrated that the incorporation
      of lower energy dense foods, such as fruit and vegetables, into children's meals
      down-regulates EI. Although a direct causal link between PS and obesity remains
      to be established, the regular consumption of larger PS of energy dense foods do
      favour obesity-promoting eating behaviours in children. Further research is
      required to establish the most feasible and effective interventions and policies
      to counteract the deleterious impact of PS and ED on children's EI. 

PMID- 24886910
TI  - Voltammetric determination of TBHQ at a glassy carbon electrode surface activated
      by in situ chemical oxidation.
AB  - In this article, a bare glassy carbon electrode (GCE) surface was directly
      activated by a simple in situ chemical method, which was characterized by
      scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray
      photoelectron spectroscopy (XPS) and cyclic voltammetry (CV), differential pulse
      voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Based on
      these results, it was found that oxygen-containing functional groups at the
      modified GCE surface were enhanced with a low damage to the surface state. Hence,
      the modified GCE exhibited an excellent performance, such as the negatively
      charged surface, good reproducibility and high selectivity. The resulting
      electrode was applied as a sensitive sensor for detection of antioxidant tertiary
      butyl hydroquinone (TBHQ), and a good linear relationship was obtained between
      the oxidation peak current and the concentration in a broad range of 1.0 MUM-1.1
      mM, with detection limits of 67 nM (S/N = 3) by DPV. Electrochemical parameters
      of TBHQ on the resulting GCE were also investigated, suggesting that the modified
      GCE could promote electron transfer kinetics towards the electrochemical reaction
      of TBHQ. Besides, the present method was used for determination of TBHQ in
      jatropha biodiesel with recovery ranging from 95.2% to 103.2%. 

PMID- 24886907
TI  - Early white matter changes in CADASIL: evidence of segmental intramyelinic oedema
      in a pre-clinical mouse model.
AB  - INTRODUCTION: Small vessel disease (SVD) of the brain is a leading cause of age-
      and hypertension-related cognitive decline and disability. Cerebral white matter
      changes are a consistent manifestation of SVD on neuroimaging, progressing
      silently for many years before becoming clinically evident. The pathogenesis of
      these changes remains poorly understood, despite their importance. In particular,
      their pathological correlate at early stages remains largely undefined. Cerebral
      Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
      (CADASIL), caused by dominant mutations of the NOTCH3 receptor, is regarded as a
      paradigm for the most common form of sporadic SVD. In this study, we used
      immunohistochemistry, confocal microscopy and electron microscopy, together with
      qualitative and quantitative analyses to assess oligodendroglial, axon and myelin
      damage in TgPAC-Notch3R169C mice, a model of preclinical CADASIL. RESULTS: The
      principal cerebral white matter changes in TgPAC-Notch3R169C mice are
      microvacuoles (<= 1 MUm diameter) in the myelin sheaths associated with focal
      myelin degradation and occurring in the absence of oligodendrocyte loss. Half the
      damaged myelin sheaths still contain an apparently intact axon. Clearance of
      myelin debris appears inefficient, as demonstrated by the significant but mild
      microglial reaction, with occasional myelin debris either contacted or
      internalized by microglial cells. CONCLUSION: Our findings suggest that segmental
      intramyelinic oedema is an early, conspicuous white matter change in CADASIL.
      Brain white matter intramyelinic oedema is consistently found in patients and
      mouse models with compromised ion and water homeostasis. These data provide a
      starting point for novel mechanistic studies to investigate the pathogenesis of
      SVD-related white matter changes.

PMID- 24886908
TI  - The preclinical Alzheimer cognitive composite: measuring amyloid-related decline.
AB  - IMPORTANCE: As Alzheimer disease (AD) research moves to intervene in
      presymptomatic phases of the disease, we must develop outcome measures sensitive
      to the earliest disease-related changes. OBJECTIVE: To demonstrate the
      feasibility of a cognitive composite outcome for clinically normal elderly
      participants with evidence of AD pathology using the ADCS Preclinical Alzheimer
      Cognitive Composite (ADCS-PACC). The ADCS-PACC combines tests that assess
      episodic memory, timed executive function, and global cognition. The ADCS-PACC is
      the primary outcome measure for the first clinical trial in preclinical AD (ie,
      the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study). DESIGN, SETTING,
      AND PARTICIPANTS: With the ADCS-PACC, we derive pilot estimates of amyloid
      related decline using data from 2 observational studies conducted in North
      America and another conducted in Australia. The participants analyzed had normal
      cognition and mean ages of 75.81, 71.37, and 79.42 years across the 3 studies.
      MAIN OUTCOMES AND MEASURES: For the 2 studies that collected data on Abeta levels
      (ADNI and AIBL), we estimate decline in a preclinical AD "Abeta-positive" placebo
      group and compare them with an "Abeta-negative" group. For the study that did not
      include data on Abeta levels (the ADCS Prevention Instrument [ADCS-PI] study), we
      grouped participants by the presence of APOE-epsilon4 and by clinical
      progression. RESULTS: In ADNI, Abeta-positive participants showed more decline
      than did Abeta-negative participants with regard to the ADCS-PACC score at 24
      months (mean [SE] difference, -1.239 [0.522] [95% CI, -2.263 to -0.215]; P =
      .02). In AIBL, the mean (SE) difference is significant at both 18 months (-1.009
      [0.406] [95% CI, -1.805 to -0.213]; P = .01) and 36 months (-1.404 [0.452] [95%
      CI, -2.290 to -0.519]; P = .002). In the ADCS-PI study, APOE-epsilon4 allele
      carriers performed significantly worse on the ADCS-PACC at 24 months (mean [SE]
      score, -0.742 [0.294] [95% CI, -1.318 to -0.165]; P = .01) and 36 months (-1.531
      [0.469] [95% CI, -2.450 to -0.612]; P = .001). In the ADCS-PI study, cognitively
      normal participants who progress from a global Clinical Dementia Rating score of
      0 are significantly worse on the ADCS-PACC than cognitively normal participants
      who are stable with a global Clinical Dementia Rating score of 0 at months 12,
      24, and 36 (mean [SE] ADCS-PACC score, -4.471 [0.702] [95% CI, -5.848 to -3.094];
      P < .001). Using pilot estimates of variance and assuming 500 participants per
      group with 30% attrition and a 5% alpha level, we project 80% power to detect
      effects in the range of Delta = 0.467 to 0.733 on the ADCS-PACC. CONCLUSIONS AND
      RELEVANCE: Analyses of at-risk cognitively normal populations suggest that we can
      reliably measure the first signs of cognitive decline with the ADCS-PACC. These
      analyses also suggest the feasibility of secondary prevention trials.

PMID- 24886913
TI  - Performance-enhancing methods for Au film over nanosphere surface-enhanced Raman
      scattering substrate and melamine detection application.
AB  - A new high-performance surface-enhanced Raman scattering (SERS) substrate with
      extremely high SERS activity was produced. This SERS substrate combines the
      advantages of Au film over nanosphere (AuFON) substrate and Ag nanoparticles
      (AgNPs). A three order enhancement of SERS was observed when Rhodamine 6G (R6G)
      was used as a probe molecule to compare the SERS effects of the new substrate and
      commonly used AuFON substrate. These new SERS substrates can detect R6G down to 1
      nM. The new substrate was also utilized to detect melamine, and the limit of
      detection (LOD) is 1 ppb. A linear relationship was also observed between the
      SERS intensity at Raman peak 682 cm(-1) and the logarithm of melamine
      concentrations ranging from 10 ppm to 1 ppb. This ultrasensitive SERS substrate
      is a promising tool for detecting trace chemical molecules because of its simple
      and effective fabrication procedure, high sensitivity and high reproducibility of
      the SERS effect.

PMID- 24886911
TI  - A meta analysis of lumbar spinal fusion surgery using bone morphogenetic proteins
      and autologous iliac crest bone graft.
AB  - BACKGROUND: Bone morphogenetic protein (BMPs) as a substitute for iliac crest
      bone graft (ICBG) has been increasingly widely used in lumbar fusion. The purpose
      of this study is to systematically compare the effectiveness and safety of fusion
      with BMPs for the treatment of lumbar disease. METHODS: Cochrane review methods
      were used to analyze all relevant randomized controlled trials (RCTs) published
      up to nov 2013. RESULTS: 19 RCTs (1,852 patients) met the inclusion criteria.
      BMPs group significantly increased fusion rate (RR: 1.13; 95% CI 1.05-1.23, P =
      0.001), while there was no statistical difference in overall success of clinical
      outcomes (RR: 1.04; 95% CI 0.95-1.13, P = 0.38) and complications (RR: 0.96; 95%
      CI 0.85-1.09, p = 0.54). A significant reduction of the reoperation rate was
      found in BMPs group (RR: 0.57; 95% CI 0.42-0.77, p = 0.0002). Significant
      difference was found in the operating time (MD-0.32; 95% CI-0.55, -0.08; P =
      0.009), but no significant difference was found in the blood loss, the hospital
      stay, patient satisfaction, and work status. CONCLUSION: Compared with ICBG, BMPs
      in lumbar fusion can increase the fusion rate, while reduce the reoperation rate
      and operating time. However, it doesn't increase the complication rate, the
      amount of blood loss and hospital stay. No significant difference was found in
      the overall success of clinical outcome of the two groups.

PMID- 24886912
TI  - Resequencing the susceptibility gene, ITGAM, identifies two functionally
      deleterious rare variants in systemic lupus erythematosus cases.
AB  - INTRODUCTION: The majority of the genetic variance of systemic lupus
      erythematosus (SLE) remains unexplained by the common disease-common variant
      hypothesis. Rare variants, which are not detectable by genome-wide association
      studies because of their low frequencies, are predicted to explain part of this
      "missing heritability." However, recent studies identifying rare variants within
      known disease-susceptibility loci have failed to show genetic associations
      because of their extremely low frequencies, leading to the questioning of the
      contribution of rare variants to disease susceptibility. A common (minor allele
      frequency = 17.4% in cases) nonsynonymous coding variant rs1143679 (R77H) in
      ITGAM (CD11b), which forms half of the heterodimeric integrin receptor,
      complement receptor 3 (CR3), is robustly associated with SLE and has been shown
      to impair CR3-mediated phagocytosis. METHODS: We resequenced ITGAM in 73 SLE
      cases and identified two previously unidentified, case-specific nonsynonymous
      variants, F941V and G1145S. Both variants were genotyped in 2,107 and 949
      additional SLE cases, respectively, to estimate their frequencies in a disease
      population. An in vitro model was used to assess the impact of F941V and G1145S,
      together with two nonsynonymous ITGAM polymorphisms, A858V (rs1143683) and M441T
      (rs11861251), on CR3-mediated phagocytosis. A paired two-tailed t test was used
      to compare the phagocytic capabilities of each variant with that of wild-type
      CR3. RESULTS: Both rare variants, F941V and G1145S, significantly impair CR3
      mediated phagocytosis in an in vitro model (61% reduction, P = 0.006; 26%
      reduction, P = 0.0232). However, neither of the common variants, M441T and A858V,
      had an effect on phagocytosis. Neither rare variant was observed again in the
      genotyping of additional SLE cases, suggesting that their frequencies are
      extremely low. CONCLUSIONS: Our results add further evidence to the functional
      importance of ITGAM in SLE pathogenesis through impaired phagocytosis.
      Additionally, this study provides a new example of the identification of rare
      variants in common-allele-associated loci, which, because of their extremely low
      frequencies, are not statistically associated. However, the demonstration of
      their functional effects adds support to their contribution to disease risk, and
      questions the current notion of dismissing the contribution of very rare variants
      on purely statistical analyses.

PMID- 24886914
TI  - The two main forms of histiocytic sarcoma in the predisposed Flatcoated retriever
      dog display variation in gene expression.
AB  - Examination of gene functions in specific tumor types improves insight in
      tumorigenesis and helps design better treatments. Due to the rarity of
      histiocytic/dendritic cell sarcoma in humans, it is difficult to accrue such
      knowledge. Therefore, comparative research of these cancers in predisposed dog
      breeds, such as the Flatcoated retriever, can be of value. Histiocytic sarcoma in
      the dog can be grouped into a soft tissue- and visceral form. The soft tissue
      form at first is localized, while the visceral form progresses more quickly to a
      terminal state, which might be related to variations in gene expression.
      Microarray analyses were performed on fresh-frozen tissue from Flatcoated
      retrievers with either soft tissue- or visceral histiocytic sarcoma. Expression
      differences of ten most significantly differentially expressed genes were
      validated with quantitative real-time PCR (q PCR) analyses. Q PCR analyses
      confirmed the significantly aberrant expression of three of the selected genes:
      C6 was up-regulated; CLEC12A and CCL5 were down-regulated in the visceral
      histiocytic sarcoma compared to the soft tissue form. The findings of our study
      indicate that these two forms of histiocytic sarcoma in the dog display a
      variation in gene expression and warrant analysis of functional changes in the
      expression of those genes in these rare sarcomas in man. 

PMID- 24886915
TI  - Shared cognitive impairments and aetiology in ADHD symptoms and reading
      difficulties.
AB  - BACKGROUND: Twin studies indicate that the frequent co-occurrence of attention
      deficit hyperactivity disorder (ADHD) symptoms and reading difficulties (RD) is
      largely due to shared genetic influences. Both disorders are associated with
      multiple cognitive impairments, but it remains unclear which cognitive
      impairments share the aetiological pathway, underlying the co-occurrence of the
      symptoms. We address this question using a sample of twins aged 7-10 and a range
      of cognitive measures previously associated with ADHD symptoms or RD. METHODS: We
      performed multivariate structural equation modelling analyses on parent and
      teacher ratings on the ADHD symptom domains of inattention and hyperactivity,
      parent ratings on RD, and cognitive data on response inhibition (commission
      errors, CE), reaction time variability (RTV), verbal short-term memory (STM),
      working memory (WM) and choice impulsivity, from a population sample of 1312
      twins aged 7-10 years. RESULTS: Three cognitive processes showed significant
      phenotypic and genetic associations with both inattention symptoms and RD: RTV,
      verbal WM and STM. While STM captured only 11% of the shared genetic risk between
      inattention and RD, the estimates increased somewhat for WM (21%) and RTV (28%);
      yet most of the genetic sharing between inattention and RD remained unaccounted
      for in each case. CONCLUSION: While response inhibition and choice impulsivity
      did not emerge as important cognitive processes underlying the co-occurrence
      between ADHD symptoms and RD, RTV and verbal memory processes separately showed
      significant phenotypic and genetic associations with both inattention symptoms
      and RD. Future studies employing longitudinal designs will be required to
      investigate the developmental pathways and direction of causality further.

PMID- 24886916
TI  - Shading as a control method for invasive European frogbit (Hydrocharis morsus
      ranae L.).
AB  - Invasive European frogbit (Hydrocharis morsus-ranae L.) has negative
      environmental and economic impacts in North American water bodies. It is
      therefore important to develop effective management tools to control this
      invasive species. This study investigated shading as a control method for
      European frogbit in both greenhouse and lake mesocosm experiments. A series of
      shade treatments (0%, 50%, 60%, 70%, 80%, and 100%) were tested in the greenhouse
      for three weeks. Results showed that the 100% shade was most effective at
      controlling European frogbit, and other shade treatments greater than 50% were
      less effective, reducing frogbit biomass up to 38.2%. There were no differences
      found in temperature between treatments, but dissolved oxygen decreased as
      shading increased. A lake mesocosm experiment utilizing 0% shade, 70% shade, and
      100% shade treatments was performed in a sheltered inlet of Oneida Lake in New
      York State for over one month. Resulting European frogbit biomass was
      significantly (25 times) less in areas treated with the 70% shade and nearly zero
      with the 100% shade. Shading did not affect temperature but improved DO
      conditions. Results on the shading effects on submerged macrophytes were not
      conclusive: no significant differences in changes in species richness and
      abundance between the three groups at the end of studied period suggested no
      shading effects; significant differences between the beginning and end
      communities in the 70% shade and the 100% shade but not in the control group
      indicated significant impacts of shading. This study is the first one to
      investigate shading as a control method for European frogbit and it is concluded
      that a moderately high density shade can effective remove European frogbit likely
      with minor impacts on the environment. More experiments with larger scales and
      longer time periods are recommended for further investigation. 

PMID- 24886917
TI  - Sport modality affects bradycardia level and its mechanisms of control in
      professional athletes.
AB  - We investigated the influence of sport modalities in resting bradycardia and its
      mechanisms of control in highly trained athletes. In addition, the relationships
      between bradycardia mechanisms and cardiac structural adaptations were tested.
      Professional male athletes (13 runners, 11 cyclists) were evaluated. Heart rate
      (HR) was recorded at rest on beat-to-beat basis (ECG). Selective pharmacological
      blockade was performed with atropine and esmolol. Vagal effect, intrinsic heart
      rate (IHR), parasympathetic (n) and sympathetic (m) modulations, autonomic
      influence (AI) and autonomic balance (Abal) were calculated. Plasmatic
      norepinephrine (high-pressure liquid chromatography) and cardiac structural
      adaptations (echocardiography) were evaluated. Runners presented lower resting
      HR, higher vagal effect, parasympathetic modulation (n), AI and IHR than cyclists
      (P<0.05). Abal, sympathetic modulation (m) and norepinephrine level were similar
      within athletes regardless of modality. The cardiac chambers were also similar
      between runners and cyclists (P=0.30). However, cyclists displayed higher septum
      and posterior wall thickness than runners (P=0.04). Further analysis showed a
      trend towards inverse correlation between IHR with septum wall thickness and
      posterior wall thickness (P=0.056). Type of sport influences the resting
      bradycardia level and its mechanisms of control in professional athletes. Resting
      bradycardia in runners is mainly dependent on an autonomic mechanism. In
      contrast, a cyclist's resting bradycardia relies on a non-autonomic mechanism
      probably associated with combined eccentric and concentric hypertrophy. 

PMID- 24886918
TI  - The impact of a 24-h ultra-marathon on salivary antimicrobial protein responses.
AB  - Depressed oral respiratory mucosal immunity and increased incidence of upper
      respiratory symptoms are commonly reported after bouts of prolonged exercise. The
      current study observed the impact of a 24-h continuous overnight ultra-marathon
      competition (distance range: 122-208 km; ambient temperature range: 0-20  degrees
      C) on salivary antimicrobial protein responses and incidence of upper respiratory
      symptoms. Body mass, unstimulated saliva and venous blood samples were taken from
      ultra-endurance runners (n=25) and controls (n=17), before and immediately after
      competition. Upper respiratory symptoms were assessed during and until 4-weeks
      after event completion. Samples were analyzed for salivary IgA, lysozyme, alpha
      amylase and cortisol in addition to plasma osmolality. Decreased saliva flow rate
      (p<0.001), salivary IgA (p<0.001) and lysozyme (p=0.015) secretion rates, and
      increased salivary alpha-amylase secretion rate (p<0.001) and cortisol responses
      (p<0.001) were observed post-competition in runners, with no changes being
      observed in controls. No incidences of upper respiratory symptoms were reported
      by participants. A 24-h continuous overnight ultra-marathon resulted in the
      depression of some salivary antimicrobial protein responses, but no incidences of
      upper respiratory symptoms were evident during or following competition. Salivary
      antimicrobial protein synergism, effective management of non-infectious episodes,
      maintaining euhydration, and (or) favourable environmental influences could have
      accounted for the low prevalence of upper respiratory symptoms.

PMID- 24886919
TI  - Injuries and overuse syndromes in competitive and elite bodybuilding.
AB  - Competitive bodybuilding is a weightlifting sport similar to powerlifting,
      strongman competition and Olympic weightlifting, which aims to increase muscle
      mass, symmetry, and body definition. Although data regarding rates of injury,
      overuse syndromes and pain during routine training is available for these other
      disciplines, it is rare for competitive bodybuilding. The aim of this study was
      to investigate rates of injury, pain during workouts and/or overuse syndromes, as
      well as the influence of particular intrinsic and external factors. Data was
      collected using questionnaires from 71 competitive and elite bodybuilders. The
      information included training routines and prior injuries. Participants were
      recruited from bodybuilding clubs in Germany. 45.1% of athletes reported symptoms
      while training. The overall injury rate was computed to be 0.12 injuries per
      bodybuilder per year (0.24 injuries per 1 000 h of bodybuilding). Athletes over
      40 exhibited higher rates of injury (p=0.029). Other investigated parameters
      showed no effects. Most injuries occurred in the shoulder, elbow, lumbar spine
      and knee regions. A large proportion of bodybuilders complained of pain not
      resulting in interruptions of training/competition. The injury rate is low
      compared to other weightlifting disciplines such as powerlifting, Olympic
      weightlifting or strongman competition. In comparison to team or contact sports
      the injury rate is minimal. 

PMID- 24886920
TI  - Effect of a single bout of resistance exercise on arterial stiffness following a
      high-fat meal.
AB  - Consumption of a high-fat meal (HFM) causes postprandial lipemia and vascular
      dysfunction. Acute resistance exercise (RE) alone may also have a negative effect
      on vascular function. The purpose of this study was to measure arterial stiffness
      and postprandial lipemia after a HFM with or without acute RE. 9 recreationally
      active men (age 24+/-5 years, BMI 25+/-3 kg/m2) completed both: (1) HFM alone and
      (2) HFM+RE in a randomized order. Pulse wave velocity (PWV) from carotid to
      femoral artery and carotid to radial artery were used as measures of
      central/aortic and peripheral arterial stiffness, respectively. Circulating
      triglycerides (TRG) were obtained from finger stick samples as a marker of
      lipemia. There was a significant condition-by-time interaction for TRG (p<0.05).
      TRG levels increased significantly following both conditions with a significantly
      attenuated increase following HFM+RE (p<0.05). There was a significant condition
      by-time interaction for peripheral PWV as this parameter increased following HFM,
      but decreased following HFM+RE (p=0.021). Central PWV did not change with HFM or
      HFM+RE (p>0.05). Following a HFM, acute RE attenuates postprandial lipemia and
      improves peripheral arterial stiffness without having a negative effect on
      central arterial stiffness.

PMID- 24886921
TI  - Inter-limb changes in arterial function after intense cycling exercise.
AB  - We investigated whether muscle exercise, by inducing a subsequent local response,
      alters local and systemic arterial function differently. Eleven healthy
      volunteers (31+/-8 years) performed a 45-min cycling session at a heart rate
      corresponding to 10% above ventilatory threshold. Measurements were performed
      before and 45 min after exercise. Central and peripheral blood pressures were
      assessed by applanation tonometry and automatic sphygmomanometer, respectively.
      Brachial and popliteal arterial changes in diameter and blood flow were assessed
      using ultrasonography. The endothelium-dependent function was assessed
      simultaneously on brachial and popliteal arteries by flow-mediated dilation.
      Systolic blood pressure decreased significantly in both upper and lower limbs as
      well as centrally. Ankle-brachial index decreased significantly. Cross-sectional
      area and blood flow of popliteal and brachial arteries increased significantly.
      The increase in blood flow was higher in the brachial than in the popliteal
      artery, whereas diameter increase was of similar magnitude between the two
      arteries. When normalized with shear rate, brachial flow-mediated dilation was
      significantly greater, whereas popliteal flow-mediated dilation was similar post-
      vs. pre-exercise. After an acute bout of intense cycling, blood flow increase and
      endothelial function were greater in the non-exercised upper limb compared to the
      exercised lower limb, suggesting that anaerobic exercise blunts the enhancement
      of systemic endothelium-dependant vasodilation in active muscle beds. 

PMID- 24886922
TI  - Lifetime physical activity, neuromuscular performance and body composition in
      healthy young men.
AB  - The purpose of the current study was to determine the relationships between
      lifetime physical activity participation, neuromuscular performance and body
      composition in men at musculoskeletal maturity. 50 healthy men (age 25.2+/-4.5
      years) volunteered to participate. Lifetime physical activity was determined from
      the Bone-specific Physical Activity Questionnaire. Impulse generated during a
      maximal vertical jump was calculated as an index of neuromuscular performance.
      Bone mineral density (BMD), lean and fat mass were determined from dual-energy x
      ray absorptiometry (XR800, Norland). A subsample of participants (n=13)
      additionally underwent peripheral quantitative computed tomography (pQCT,
      XCT3000, Stratec) measures. Results demonstrated that those in the highest
      tertile for lifetime physical activity exhibited the greatest lumbar spine BMD
      (udiff=0.12 g/cm2, p=0.005) and lean body mass index (LBMI) (p=0.04). Those in
      the highest tertile for impulse also exhibited the highest whole body (udiff=0.08
      g/cm2), lumbar spine (udiff=0.14 g/cm2), and femoral neck BMD (udiff=0.15 g/cm2)
      (p<=0.05). All BMD differences exceeded the least significant change. Childhood
      physical activity was positively related to LBMI (r=0.28, p=0.05), whereas
      sedentary activity was inversely related to femoral neck BMD (r=-0.33, p=0.02).
      Results support recommendations for sustained physical activity participation
      during the growing years.

PMID- 24886923
TI  - Neural network for estimating energy expenditure in paraplegics from heart rate.
AB  - The aim of the present study is to obtain models for estimating energy
      expenditure based on the heart rates of people with spinal cord injury without
      requiring individual calibration. A cohort of 20 persons with spinal cord injury
      performed a routine of 10 activities while their breath-by-breath oxygen
      consumption and heart rates were monitored. The minute-by-minute oxygen
      consumption collected from minute 4 to minute 7 was used as the dependent
      variable. A total of 7 features extracted from the heart rate signals were used
      as independent variables. 2 mathematical models were used to estimate the oxygen
      consumption using the heart rate: a multiple linear model and artificial neural
      networks. We determined that the artificial neural network model provided a
      better estimation (r=0.88, MSE=4.4 ml . kg(-1) . min(-1)) than the multiple
      linear model (r=0.78; MSE=7.63 ml . kg(-1) . min(-1)).The goodness of fit with
      the artificial neural network was similar to previous reported linear models
      involving individual calibration. In conclusion, we have validated the use of the
      heart rate to estimate oxygen consumption in paraplegic persons without
      individual calibration and, under this constraint, we have shown that the
      artificial neural network is the mathematical tool that provides the better
      estimation. 

PMID- 24886924
TI  - Maximal lactate steady state in kayaking.
AB  - A fixed blood lactate value of 4 mM was commonly used to calculate workload at
      maximal lactate steady state (MLSS) in kayaking. Our purpose was to measure the
      actual blood lactate value at MLSS and workload at MLSS in kayaking and assess
      the validity of using a fixed blood lactate value to calculate the workload at
      MLSS. 8 junior kayakers (15.1+/-1.2 years; 179.9+/-7.3 cm; 72.3+/-4.9 kg)
      participated in an incremental workload test and 4-6 sub-maximal constant
      workload tests (duration of 30 min) on a kayaking ergometer. Blood lactate was
      measured to calculate the blood lactate value and workload at MLSS. The blood
      lactate value at MLSS in kayaking was 5.4+/-0.7 mM. The measured workload at MLSS
      (112+/-22 watts) was significantly greater than the calculated workload using a
      lactate value of 4 mM (104+/-18 watts, p=0.016). The measured MLSS workload was
      not significantly different from the calculated workload using a fixed lactate
      value of 5.4 mM (115+/-19 watts, p=0.16) or 5.0 mM (113+/-19 watts, p=0.78) in
      the incremental tests. A fixed blood lactate value of 5 mM instead of 4 mM might
      be a better estimate in kayaking given the incremental workload test used in this
      study. 

PMID- 24886925
TI  - Comparison of intensities and rest periods for VO2max verification testing
      procedures.
AB  - We sought to determine the incidence of 'true' VO2max confirmation with the
      verification procedure across different protocols. 12 active participants (men
      n=6, women n=6) performed in random order 4 different maximal graded exercises
      tests (GXT) and verification bout protocols on 4 separate days. Conditions for
      the rest period and verification bout intensity were: A - 105% intensity, 20 min
      rest; B - 105% intensity, 60 min rest; C - 115% intensity, 20 min rest; D - 115%
      intensity, 60 min rest. VO2max confirmation (difference between peak VO2 GXT and
      verification trial<+/-3%) using the verification trial was 12/12 (100%), 12/12
      (100%), 8/12 (66.70%), and 7/12 (58.33%) for protocols A, B, C, and D. There was
      a significant (p<0.05) effect of verification intensity on VO2max confirmation
      across all exercise test conditions (intensity effect within recovery 20 min
      (chi(2) (1)=4.800, p<0.05), intensity effect within recovery 60 min (chi(2)
      (1)=6.316, p<0.05)). No significant effect was found for incidence of VO2max
      confirmation with different rest periods. We recommend the use of 105% of the
      maximal GXT workload and 20 min rest periods when using verification trials to
      confirm VO2max in normally active populations. 

PMID- 24886926
TI  - Effect of movement velocity during resistance training on neuromuscular
      performance.
AB  - This study aimed to compare the effect on neuromuscular performance of 2
      isoinertial resistance training programs that differed only in actual repetition
      velocity: maximal intended (MaxV) vs. half-maximal (HalfV) concentric velocity.
      21 resistance-trained young men were randomly assigned to a MaxV (n=10) or HalfV
      (n=11) group and trained for 6 weeks using the full squat exercise. A
      complementary study (n=8) described the acute metabolic and mechanical response
      to the protocols used. MaxV training resulted in a likely more beneficial effect
      than HalfV on squat performance: maximum strength (ES: 0.94 vs. 0.54), velocity
      developed against all (ES: 1.76 vs. 0.88), light (ES: 1.76 vs. 0.75) and heavy
      (ES: 2.03 vs. 1.64) loads common to pre- and post-tests, and CMJ height (ES: 0.63
      vs. 0.15). The effect on 20-m sprint was unclear, however. Both groups attained
      the greatest improvements in squat performance at their training velocities.
      Movement velocity seemed to be of greater importance than time under tension for
      inducing strength adaptations. Slightly higher metabolic stress (blood lactate
      and ammonia) and CMJ height loss were found for MaxV vs. HalfV, while metabolite
      levels were low to moderate for both conditions. MaxV may provide a superior
      stimulus for inducing adaptations directed towards improving athletic
      performance. 

PMID- 24886927
TI  - Athletic performance and birth month: is the relative age effect more than just
      selection bias?
AB  - The aim of this study was to determine if month of birth affects performance in 3
      tests of physical function in children and adolescents. We measured
      cardiorespiratory fitness, handgrip strength and lower-body power expressed them
      relative to (whole year) age then compared scores between calendar year birth
      months. We also expressed test performance as the likelihood of achieving
      criterion-referenced fitness standards. There were significant main effects of
      birth-month for cardiorespiratory fitness (F=4.54, p<0.001), strength (F=6.81,
      p<0.001) and power (F=3.67, p<0.001). Children born in November were fitter and
      more powerful than those born at other times, particularly the summer months
      (April, May and June). October-born children were stronger than those born in all
      months except September and November. This relationship was evident despite
      controlling for decimal age and despite no significant inter-month differences in
      anthropometric characteristics.There is a clear physical advantage for those born
      in the autumn and this may explain some of the bias in sports selection
      attributed to the relative age effect, particularly when the British school-year
      (September) cut-off is used. 

PMID- 24886928
TI  - Comparison of thoracic bioimpedance with acetylene uptake for measuring cardiac
      output.
AB  - Cardiac output is shown to be a key determinant for oxygen transport, performance
      and health. Reliable and accurate non-invasive measurements of cardiac output,
      especially during exercise, are therefore of importance. The present study
      compared a new thoracic bioimpedance method with the established single-breath
      acetylene uptake method. We assessed cardiac output in 20 (24+/-4 years.)
      moderately trained males, at rest and during cycling. Both methods showed good
      test-retest reliabilities with +/-2 SD limits of agreement of 3.67 and -4.50 L ?
      min(-1) (thoracic bioimpedance) and 4.46 and -5.69 L ? min(-1) (single breath),
      respectively. When thoracic bioimpedance was compared with single breath, the +/
      2 SD limits of agreement were poor (-6.05 and 9.57 L ? min(-1)). Thoracic
      bioimpedance displayed significantly lower (p<0.05) absolute cardiac output
      values than single breath, and the cardiac output-oxygen consumption slopes
      (y=5.7x+5.5 (single breath) and y=5.0x+5.0 (thoracic bioimpedance) tended
      (p=0.08) to show less increase for thoracic bioimpedance. CONCLUSIONS: Results
      from the single-breath method are in line with previous findings, showing a good
      reliability. Although thoracic bioimpedance showed a similar reliability as the
      single-breath method, and is easier to use, the agreement with single breath was
      poor, and thoracic bioimpedance seems not to be able to replace it.

PMID- 24886929
TI  - Influence of sex and level on marathon pacing strategy. Insights from the New
      York City race.
AB  - Different pacing profiles have been identified in the literature for endurance
      sporting events: the 'positive', 'negative', 'even', 'parabolic shaped' and
      'variable pacing'. Most studies have focused on competitive or elite athletes
      (including winners) without considering more recreational runners, for many of
      whom the primary goal is simply to finish the event. The major city marathons
      provide a large heterogeneous sample to compare the pacing profiles of
      competitive vs. recreational runners, and thus to understand pacing more broadly.
      A total of 190,228 New York finishers' (69,316 women) marathon times (from 2006
      to 2011) were assessed. Although all runners developed a positive pace profile, a
      lower variability of speed through the race was found in the top runners
      (coefficient of variation (CV) for speed during 5-km splits: 7.8% (men) and 6.6%
      (women)) compared with the less successful runners (CV ranging from 8.3 to
      14.4%). Both men and women try to maintain an even pace profile along the
      marathon course, partly by avoiding an excessively fast start that might result
      in a pronounced decrease in the speed in the second half of the race.

PMID- 24886932
TI  - Systematic training in focused cardiopulmonary ultrasound affects decision-making
      in the prehospital setting - two case reports.
AB  - We present two cases from the Helicopter Emergency Medical Services (HEMS) in
      Denmark, in which prehospital physicians trained in cardiac ultrasound (FATE)
      disclosed significant pathology that induced a radical change for the critical
      patient's course.

PMID- 24886933
TI  - Protocol for a systematic review and individual participant data meta-analysis of
      B-type natriuretic peptide-guided therapy for heart failure.
AB  - BACKGROUND: Several aggregate data meta-analyses suggest that treatment guided by
      the serum concentration of natriuretic peptides (B-type natriuretic peptide (BNP)
      or its derivative N-terminal pro-B-type natriuretic peptide (NT-BNP)) reduces all
      cause mortality compared with usual care in patients with heart failure (HF). We
      propose to conduct a meta-analysis using individual participant data (IPD) to
      estimate the effect of BNP-guided therapy on clinical outcomes, and estimate the
      extent of effect modification for clinically important subgroups. METHODS: We
      will use standard systematic review methods to identify relevant trials and
      assess study quality. We will include all randomized controlled trials (RCTs) of
      BNP-guided treatment for HF that report a clinical outcome. The primary outcome
      will be time to all-cause mortality. We will collate anonymized, individual
      patient data into a single database, and carry out appropriate data checks. We
      will use fixed-effects and random-effects meta-analysis methods to combine hazard
      ratios (HR) estimated within each RCT, across all RCTs. We will also include a
      meta-analysis and meta-regression analyses based on aggregate data, and combine
      IPD with aggregate data if we obtain IPD for a subset of trials. DISCUSSION: The
      IPD meta-analysis will allow us to estimate how patient characteristics modify
      treatment benefit, and to identify relevant subgroups of patients who are likely
      to benefit most from BNP-guided therapy. This is important because aggregate meta
      analyses have suggested that clinically relevant subgroup effects exist, but
      these analyses have been unable to quantify the effects reliably or precisely.
      TRIALS REGISTRATION: PROSPERO 2013: CRD42013005335.

PMID- 24886930
TI  - The HIVToolbox 2 web system integrates sequence, structure, function and mutation
      analysis.
AB  - There is enormous interest in studying HIV pathogenesis for improving the
      treatment of patients with HIV infection. HIV infection has become one of the
      best-studied systems for understanding how a virus can hijack a cell. To help
      facilitate discovery, we previously built HIVToolbox, a web system for visual
      data mining. The original HIVToolbox integrated information for HIV protein
      sequence, structure, functional sites, and sequence conservation. This web system
      has been used for almost 40,000 searches. We report improvements to HIVToolbox
      including new functions and workflows, data updates, and updates for ease of use.
      HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2
      has new functionalities focused on HIV pathogenesis including drug-binding sites,
      drug-resistance mutations, and immune epitopes. The integrated, interactive view
      enables visual mining to generate hypotheses that are not readily revealed by
      other approaches. Most HIV proteins form multimers, and there are
      posttranslational modification and protein-protein interaction sites at many of
      these multimerization interfaces. Analysis of protease drug binding sites reveals
      an anatomy of drug resistance with different types of drug-resistance mutations
      regionally localized on the surface of protease. Some of these drug-resistance
      mutations have a high prevalence in specific HIV-1 M subtypes. Finally,
      consolidation of Tat functional sites reveals a hotspot region where there appear
      to be 30 interactions or posttranslational modifications. A cursory analysis with
      HIVToolbox2 has helped to identify several global patterns for HIV proteins. An
      initial analysis with this tool identifies homomultimerization of almost all HIV
      proteins, functional sites that overlap with multimerization sites, a global drug
      resistance anatomy for HIV protease, and specific distributions of some DRMs in
      specific HIV M subtypes. HIVToolbox2 is an open-access web application available
      at [http://hivtoolbox2.bio-toolkit.com]. 

PMID- 24886934
TI  - Response surface optimized extraction of 1-deoxynojirimycin from mulberry leaves
      (Morus alba L.) and preparative separation with resins.
AB  - In the present study, the extraction technology and preparative separation of 1
      deoxynojirimycin from mulberry leaves were systematically investigated. Four
      extraction parameters (ethanol concentration, extraction temperature, extraction
      time and ratio of solvent to sample) were explored by response surface
      methodology (RSM). The results indicated that the maximal yield of 1
      deoxynojirimycin was achieved with an ethanol concentration of 55%, extraction
      temperature of 80  degrees C, extraction time of 1.2 h and ratio of solvent to
      sample of 12:1. The extraction yield under these optimum conditions was found to
      be 256 mg/100 g dry mulberry leaves. A column packed with a selected resin was
      used to perform dynamic adsorption and desorption tests to optimize the
      separation process. The results show that the preparative separation of 1
      deoxynojirimycin from mulberry leaves can be easily and effectively done by
      adopting 732 resin. In conclusion, 732 resin is the most appropriate for the
      separation of 1-deoxynojirimycin from other components in mulberry leaves
      extracts, and its adsorption behavior can be described with Langmuir isotherms
      and a two-step adsorption kinetics model. The recovery and purity of 1
      deoxynojirimycin in the final product were 90.51% and 15.3%, respectively. 

PMID- 24886935
TI  - Mesoporous silicas with tunable morphology for the immobilization of laccase.
AB  - Siliceous ordered mesoporous materials (OMM) are gaining interest as supports for
      enzyme immobilization due to their uniform pore size, large surface area, tunable
      pore network and the introduction of organic components to mesoporous structure.
      We used SBA-15 type silica materials, which exhibit a regular 2D hexagonal
      packing of cylindrical mesopores of uniform size, for non-covalent immobilization
      of laccase. Synthesis conditions were adjusted in order to obtain supports with
      different particle shape, where those with shorter channels had higher loading
      capacity. Despite the similar isoelectric points of silica and laccase and the
      close match between the size of laccase and the pore dimensions of these SBA-15
      materials, immobilization was achieved with very low leaching. Surface
      modification of macro-/mesoporous amorphous silica by grafting of amine moieties
      was proved to significantly increase the isoelectric point of this support and
      improve the immobilization yield. 

PMID- 24886936
TI  - Synthesis and cytotoxicity of 2,3-enopyranosyl C-linked conjugates of genistein.
AB  - A series of glycoconjugates, derivatives of genistein containing a C-glycosylated
      carbohydrate moiety, were synthesized and their anticancer activity was tested in
      vitro in the human cell lines HCT 116 and DU 145. The target compounds 15-17 were
      synthesized by treating omega-bromoalkyl C-glycosides derived from L-rhamnal (1)
      with a tetrabutylammonium salt of genistein. The new, metabolically stable
      analogs of previously studied O-glycosidic genistein derivatives inhibited
      proliferation of cancer cell lines through inhibition of the cell cycle. 

PMID- 24886937
TI  - An unusual conversion of paramagnetic [3-Cl-3,3,8-{Ph2P(CH2)nPPh-u-(C6H4-ortho)}
      1,2-(CH3)2-closo-3,1,2-RuIIIC2B9H8] (n=3 and 4) to form the first 18-electron P
      phenylene ortho-cycloboronated closo-ruthenacarboranes with a dioxygen ligand.
AB  - Treatment of [3-Cl-3,3,8-[Ph2P(CH2)nPPh-u-(C6H4-ortho)]-1,2-Me2-closo-3,1,2
      RuIIIC2B9H8] (1, n=3; 2, n=4) with an excess of KOH in a 1:1 benzene/methanol
      mixture at room temperature in air affords new dioxygen closo-ruthenacarborane
      complexes [3-(eta2-O2)-3,3,8-[Ph2P(CH2)nPPh-u-(C6H4-ortho)]-1,2-Me2-closo-3,1,2
      RuIIIC2B9H8] (3, n=3) and (4, n=4) in 42.5% and 45.8% yield respectively. The
      structures of dioxygen complexes 3 and 4 were established by single-crystal X-ray
      diffraction. The IR and multinuclear NMR data [1H, 13C{1H}, 31P{1H} and 11B{1H}]
      along with 2D HSQC correlation spectra for the new dioxygen closo
      ruthenacarboranes are discussed.

PMID- 24886938
TI  - Synthesis and biological evaluation of novel 2-arylalkylthio-5-iodine-6
      substituted-benzyl-pyrimidine-4(3H)-ones as potent HIV-1 non-nucleoside reverse
      transcriptase inhibitors.
AB  - A novel series of 2-arylalkylthio-5-iodine-6-substitutedbenzyl-pyrimidine-4(3H)
      ones (S-DABOs) 8a-x had been synthesized via an efficient method. Their
      biological activity against HIV virus and RT assay were evaluated. Some
      compounds, especially 8h, 8l and 8n, displayed promising activity against HIV-1
      RT with IC50 values in a range of 0.41 MUM to 0.71 MUM, which were much better
      than that of nevirapine. Molecular modeling studies revealed that the binding
      mode would be affected via forming an additional hydrogen bond by incorporating
      an oxygen atom on the C-2 side chain. The biological activity was in accordance
      with the docking results. 

PMID- 24886939
TI  - miR-221/222 promotes S-phase entry and cellular migration in control of basal
      like breast cancer.
AB  - The miR-221/222 cluster has been demonstrated to function as oncomiR in human
      cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and
      confers tamoxifen resistance in breast cancer. However, the effects and
      mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain
      unclear. Here we detected a much higher expression of miR-221/222 in highly
      invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal
      cells. A microRNA dataset from breast cancer patients indicated an elevated
      expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was
      associated with the induction of miR-221/222 expression. miRNA inhibitors
      specially targeting miR-221 or miR-222 both significantly suppressed cellular
      migration, invasion and G1/S transition of the cell cycle in BLBC cell types.
      Proteomic analysis demonstrated the down-regulation of two tumor suppressor
      genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase
      inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR
      221/222 regulation of G1/S transition of the cell cycle. These findings
      demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.

PMID- 24886940
TI  - Acute and 4-week repeated-dose oral toxicity studies of Cirsium setidens in rats.
AB  - Cirsium setidens is a wild perennial plant species found in Korea that may have
      anti-oxidative, anti-adipogenic, and hepatoprotective activities. However,
      details of the toxicology of C. setidens remain unknown. This study was performed
      to evaluate the toxicological effects of an acute administration and 4-week
      repeated dosing of a C. setidens extract in Sprague-Dawley rats to ensure the
      safe use of this extract. C. setidens (1250, 2500, and 5000 mg/kg body
      weight/day) did not induce significant toxicological changes in groups matched by
      gender with respect to mortality, clinical signs, body weight, urinalysis,
      ophthalmoscopy, necropsy findings, hematology, and histopathology. Therefore,
      this study demonstrates that acute administration and 4-week repeated dosing of
      C. setidens extract orally using this administration protocol is safe. 

PMID- 24886941
TI  - Diethyl 2-(phenylcarbamoyl)phenyl phosphorothioates: synthesis, antimycobacterial
      activity and cholinesterase inhibition.
AB  - A new series of 27 diethyl 2-(phenylcarbamoyl)phenyl phosphorothioates
      (thiophosphates) was synthesized, characterized by NMR, IR and CHN analyses and
      evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium avium and two
      strains of Mycobacterium kansasii. The best activity against M. tuberculosis was
      found for O-{4-bromo-2-[(3,4-dichlorophenyl)carbamoyl]phenyl} O,O-diethyl
      phosphorothioate (minimum inhibitory concentration of 4 uM). The highest activity
      against nontuberculous mycobacteria was exhibited by O-(5-chloro-2-{[4
      (trifluoromethyl)phenyl]carbamoyl}-phenyl) O,O-diethyl phosphorothioate with MIC
      values from 16 uM. Prepared thiophosphates were also evaluated against
      acetylcholinesterase from electric eel and butyrylcholinesterase from equine
      serum. Their inhibitory activity was compared to that of the known
      cholinesterases inhibitors galanthamine and rivastigmine. All tested compounds
      showed a higher (for AChE inhibition) and comparable (for BChE inhibition)
      activity to that of rivastigmine, with IC50s within the 8.04 to 20.2 uM range. 

PMID- 24886942
TI  - Bis-naphtho-gamma-pyrones from fungi and their bioactivities.
AB  - Bis-naphtho-gamma-pyrones are an important group of aromatic polyketides derived
      from fungi. They have a variety of biological activities including cytotoxic,
      antitumor, antimicrobial, tyrosine kinase and HIV-1 integrase inhibition
      properties, demonstrating their potential applications in medicine and
      agriculture. At least 59 bis-naphtho-gamma-pyrones from fungi have been reported
      in the past few decades. This mini-review aims to briefly summarize their
      occurrence, biosynthesis, and structure, as well as their biological activities.
      Some considerations regarding to synthesis, production, and medicinal and
      agricultural applications of bis-naphtho-gamma-pyrones are also discussed. 

PMID- 24886944
TI  - Post-harvest induced production of salvianolic acids and significant promotion of
      antioxidant properties in roots of Salvia miltiorrhiza (Danshen).
AB  - Danshen, the dried roots of Salvia miltiorrhiza, is an extremely valued
      Traditional Chinese Medicine. Previously, we have demonstrated that salvianolic
      acid B (SaB), the important bioactive ingredient in this herb, was a post-harvest
      product. Here, we further reported that all salvianolic acids (SAs) in the roots
      were post-harvest products of the drying process. In addition, the results of
      various radical scavenging activity assays, including lipid peroxidation (1),
      DPPH (2), hydroxyl (3) and superoxide (4), were significantly increased along
      with the accumulation of total salvianolic acids in the process. The contents of
      chemical targets and antioxidant activities both reached the highest value under
      thermal treatment at 130  degrees C for 80 min. In this dehydration period,
      contents of SaB, and sum of nine SAs increased from 0.01% to 5.51%, and 0.20% to
      6.61%; and IC50 of antioxidant activity decreased from 4.85 to 2.69 (1); 7.75 to
      0.43 (2); 2.57 to 1.13 (3) and 17.25 to 1.10 mg/mL. These results further
      supported the hypothesis that the newly harvested plant roots were still
      physiologically active and the secondary metabolites might be produced due to
      dehydration stress after harvest. Our findings supplied an important and useful
      theoretical basis for promoting the quality of Danshen and other medicinal plant
      materials. 

PMID- 24886943
TI  - Effects of the total saponins from Rosa laevigata Michx fruit against
      acetaminophen-induced liver damage in mice via induction of autophagy and
      suppression of inflammation and apoptosis.
AB  - The effect of the total saponins from Rosa laevigata Michx fruit (RLTS) against
      acetaminophen (APAP)-induced liver damage in mice was evaluated in the present
      paper. The results showed that RLTS markedly improved the levels of liver SOD,
      CAT, GSH, GSH-Px, MDA, NO and iNOS, and the activities of serum ALT and AST
      caused by APAP. Further research confirmed that RLTS prevented fragmentation of
      DNA and mitochondrial ultrastructural alterations based on TdT-mediated dUTP nick
      end labeling (TUNEL) and transmission electron microscopy (TEM) assays. In
      addition, RLTS decreased the gene or protein expressions of cytochrome P450
      (CYP2E1), pro-inflammatory mediators (IL-1beta, IL-4, IL-6, TNF-alpha, iNOS, Bax,
      HMGB-1 and COX-2), pro-inflammatory transcription factors (NF-kappaB and AP-1),
      pro-apoptotic proteins (cytochrome C, p53, caspase-3, caspase-9, p-JNK, p-p38 and
      p-ERK), and increased the protein expressions of Bcl-2 and Bcl-xL. Moreover, the
      gene expression of IL-10, and the proteins including LC3, Beclin-1 and Atg5
      induced by APAP were even more augmented by the extract. These results
      demonstrate that RLTS has hepatoprotective effects through antioxidative action,
      induction of autophagy, and suppression of inflammation and apoptosis, and could
      be developed as a potential candidate to treat APAP-induced liver damage in the
      future. 

PMID- 24886945
TI  - Age and decisions to limit life support for patients with acute lung injury: a
      prospective cohort study.
AB  - INTRODUCTION: The proportion of elderly Americans admitted to the intensive care
      unit (ICU) in the last month of life is rising. Hence, challenging decisions
      regarding the appropriate use of life support are increasingly common. The
      objective of this study was to estimate the association between patient age and
      the rate of new limitations in the use of life support, independent of daily
      organ dysfunction status, following acute lung injury (ALI) onset. METHODS: This
      was a prospective cohort study of 490 consecutive patients without any
      limitations in life support at the onset of ALI. Patients were recruited from 11
      ICUs at three teaching hospitals in Baltimore, Maryland, USA, and monitored for
      the incidence of six pre-defined limitations in life support, with adjustment for
      baseline comorbidity and functional status, duration of hospitalization before
      ALI onset, ICU severity of illness, and daily ICU organ dysfunction score.
      RESULTS: The median patient age was 52 (range: 18 to 96), with 192 (39%) having a
      new limitation in life support in the ICU. Of patients with a new limitation, 113
      (59%) had life support withdrawn and died, 53 (28%) died without resuscitation,
      and 26 (14%) survived to ICU discharge. Each ten-year increase in patient age was
      independently associated with a 24% increase in the rate of limitations in life
      support (Relative Hazard 1.24; 95% CI 1.11 to 1.40) after adjusting for daily ICU
      organ dysfunction score and all other covariates. CONCLUSIONS: Older critically
      ill patients are more likely to have new limitations in life support independent
      of their baseline status, ICU-related severity of illness, and daily organ
      dysfunction status. Future studies are required to determine whether this
      association is a result of differences in patient preferences by age, or
      differences in the treatment options discussed with the families of older versus
      younger patients.

PMID- 24886947
TI  - Italian community psychiatry in practice: description and comparison of three
      regional systems.
AB  - The psychiatric reform in 1978 assigned the regions the task of implementing
      community mental health (MH) services; 30 years on in Italy, there are as many MH
      systems as there are Italian regions and all completely differentiated. Three
      Italian regions (Lombardy, Emilia-Romagna, and Campania) in different geographic
      areas are here chosen as representing three different models of community care
      implementation as well as certain similarities and differences at a regional
      level. For each region, the article focuses on MH policy, financing, the network
      of community health facilities, service provision, MH staff, and the information
      system. 

PMID- 24886946
TI  - Looking back: Italian psychiatry from its origins to Law 180 of 1978.
AB  - Italian psychiatry is usually renowned for the radical anti-institutional
      movement and the Reform Law of 1978, which requires a historical analysis to
      understand. In the 1960s, Italian psychiatric culture had reached a deadlock
      because of its obsolete biological, strictly neuroanatomical, explanatory
      approach (so-called organicism) postulated by academic institutions and awkwardly
      implemented in asylum practice. One prominent figure in shaping this philosophy
      was Cesare Lombroso, internationally known as the father of criminal
      anthropology. This attitude became sharper and more oppressive during the Fascist
      regime, where international exchanges and collaboration were discouraged when not
      repressed. Thus, anachronistic was the situation in the 1960s that the anti
      institutional movement founded and led by Franco Basaglia swept professionals,
      politicians, and public opinion in its wake. What, in most countries, took the
      form of gradual reform became a radical reaction in Italy and, in less than 20
      years, turned one of the most deprived institutional systems into the most
      radical community mental health care system in the world. 

PMID- 24886948
TI  - Involvement of users and relatives in mental health service evaluation.
AB  - Although Italian mental health (MH) services are community based, user and
      relative participation in service evaluation lagged behind until lately. We here
      review three recent studies involving stakeholder participation in service
      evaluation: two were quantitative studies, one on 204 users in an MH service in
      Pistoia (Central Italy) and the other on 2259 relatives, conducted with the
      National Union of Associations for Mental Health. The third (supported by The
      Centro per il Controllo delle Malattie, the ministerial Center for Disease
      Control) was a qualitative study in seven MH services, involving users,
      relatives, and professionals together, which collected interviews from 136 users,
      119 relatives, and 79 professionals. In the quantitative studies, positive
      evaluations outnumbered negative ones. The qualitative study explored negative
      aspects in greater depth. Common findings were insufficient information,
      underinvolvement of users-relatives in planning, no choice of clinician,
      psychiatrist domination, and limited helpfulness of interventions. With
      stakeholder participation in service evaluation, the present medical framework
      will need reshaping. 

PMID- 24886949
TI  - Outcomes from Italian community psychiatric services studies.
AB  - Outcome measurement, to be valid, reliable, and useful to both program planning
      and evaluation of interventions, should be based on the principle of
      multiaxiality (i.e., considering the perspectives of all those involved in the
      care process, including clinicians, patients, caregivers, users' representatives,
      third-party payers) and of multidimensionality (i.e., considering an
      intervention's effect on various dimensions of patients' life, including clinical
      outcomes such as psychopathology, disability, and needs for care and self
      perceived outcomes such as quality of life and service satisfaction).
      Unfortunately, in Italy, this methodology has not been applied on a large scale.
      However, some Italian centers with a long-lasting tradition in the area of
      psychiatric epidemiology have provided evidence that outcome assessment in
      routine practice is not only sustainable but also advantageous in the medium- and
      long-term. This article summarizes the results obtained in some of these studies,
      including three longitudinal studies on the outcome of community psychiatric care
      promoted by the research group of South Verona, such as the South Verona Outcome
      Project, the Psychosis Incident Cohort Outcome Study, and the Genetics
      Endophenotypes and Treatment: Understanding early Psychosis - &bullet; Psychosis:
      early Intervention and Assessment of Needs and Outcome trial.Implementation of
      routine outcome assessment can lead-and to a certain extent has already led-to a
      cultural change among Italian mental health service staff members, to facilitate
      a) the establishment of a revision-of-practice process, b) greater acceptance of
      the importance of evidence, and a predisposition to put it into practice. 

PMID- 24886950
TI  - Community mental health care in the future: nine proposals.
AB  - The aim of this article was to put community psychiatry into a longitudinal and
      global perspective and to try to look into the future. Specifically, we set out
      the following nine proposals:1. Central and regional government should measure
      the treated percentage of people with mental illness (coverage) and set specific
      targets to increase coverage over set time periods.2. Health care services need
      to recognize the far lower life expectancy among people with mental disorders and
      develop and evaluate new methods to reduce this health disparity.3. Mental health
      services should provide specific modules to reduce stigma and discrimination
      experienced by people with mental illness.4. Mental health staff should provide
      care that service users (and their family members) find accessible and
      acceptable.5. Mental health care should consist of a careful balance of hospital
      and community care, with most care provided at or near people's homes.6. Mental
      health planners, both in times of economic growth and recession, should invest in
      treatments known to be effective and disinvest from treatments known to be
      ineffective or even harmful.7. Mental health staff and service users should
      develop and evaluate methods to improve shared decision making.8. Health care
      practitioners (of western and nonwestern traditions) should take practical steps
      to see each other as partners in an integrated system that increases the total
      amount of mental health care available, while ensuring that only effective and
      acceptable treatments are provided.9. Mental health services should develop
      dedicated programs for recovery: this implies that staff understand an
      individual's personal recovery goals and fully support his/her achievement. 

PMID- 24886951
TI  - Nail disorders in infants and children.
AB  - PURPOSE OF REVIEW: Nail diseases in infants and children are an uncommon cause of
      consultation and are often difficult to diagnose and to manage. This review will
      cover nail diseases that are most commonly seen in clinical practice, including
      congenital and hereditary disorders and inflammatory, infective, and neoplastic
      nail diseases. The purpose of the review is to help the reader to recognize nail
      disorders at an early age and to manage them appropriately. RECENT FINDINGS: Two
      recent large studies have reported the clinical findings of genetic disorders
      involving the nails, that is, pachyonychia congenita and epidermolysis bullosa.
      Only a few articles gave a comprehensive review of a disease, as occurred for
      onychomycosis, while the majority of the reports published in the recent
      literature involve single cases. SUMMARY: Nail diseases in children and neonates
      are not easy to diagnose by nonexperts. Basic knowledge of the anatomy and
      biology of the nail facilitates their diagnosis as the understanding of their
      pathophysiology. This review gives hints at the most common nail diseases that
      affect infants and children.

PMID- 24886952
TI  - Adolescent health literacy and the Internet: challenges and opportunities.
AB  - PURPOSE OF REVIEW: Adolescents have increasingly turned to the Internet as a
      resource for insight into their health questions and concerns. However, the
      extent to which adolescents will benefit from using the Internet as a source for
      health information will be determined in great part by their level of media
      literacy and health literacy. The purpose of this review is to explore challenges
      that adolescents face when using the Internet to access health information and
      opportunities for intervention. RECENT FINDINGS: Adolescents must be able to
      access, understand, analyze, and evaluate health information on the Internet and
      then apply this information to make appropriate health decisions. Challenges
      faced by adolescents fall into the realm of functional literacy (e.g., not being
      able to spell a medical term needed in a search), critical literacy (e.g., not
      being able to differentiate accurate from inaccurate online health information),
      and, lastly, interactive literacy (e.g., translating online health information to
      appropriate health behaviors). SUMMARY: More research is needed in this field to
      better understand the challenges and to propose effective solutions. However, a
      multifaceted approach that engages policymakers, educators, healthcare providers,
      online health information providers, and parents may be positioned to make the
      largest impact.

PMID- 24886953
TI  - New insights into the allergic march.
AB  - PURPOSE OF REVIEW: The allergic march of childhood describes an association
      between atopic dermatitis, IgE-mediated food allergy, allergic asthma, and
      allergic rhinitis that begins with an atopic family history. This review
      summarizes recent insights into the nature of these conditions and their
      associations. RECENT FINDINGS: In recent years, common allergic diseases have
      become more prevalent and increased rates of food allergies remain incompletely
      understood. This review explores a newly described major genetic risk factor, a
      mutation in the skin matrix protein filaggrin, as it relates to the allergic
      march of childhood. New paradigms of understanding the interrelationships between
      atopic dermatitis, food allergy, and asthma are described. A surge of
      investigative effort has been directed toward the prevention and treatment of
      food allergy. Risk factors for allergic asthma in young children have been used
      to predict patient response to treatment. A recent practice parameter on furry
      animal/pet avoidance updates current understanding of allergen avoidance in
      modifying allergic phenotypes. SUMMARY: Understanding of the interrelationships
      of atopic diseases allows earlier diagnosis of allergic conditions in at-risk
      patient populations and may lead to novel approaches to health promotion and
      disease prevention.

PMID- 24886955
TI  - Direct synthesis of formic acid from carbon dioxide by hydrogenation in acidic
      media.
AB  - The chemical transformation of carbon dioxide into useful products becomes
      increasingly important as CO2 levels in the atmosphere continue to rise as a
      consequence of human activities. In this article we describe the direct
      hydrogenation of CO2 into formic acid using a homogeneous ruthenium catalyst, in
      aqueous solution and in dimethyl sulphoxide (DMSO), without any additives. In
      water, at 40  degrees C, 0.2 M formic acid can be obtained under 200 bar,
      however, in DMSO the same catalyst affords 1.9 M formic acid. In both solvents
      the catalysts can be reused multiple times without a decrease in activity.
      Worldwide demand for formic acid continues to grow, especially in the context of
      a renewable energy hydrogen carrier, and its production from CO2 without base,
      via the direct catalytic carbon dioxide hydrogenation, is considerably more
      sustainable than the existing routes. 

PMID- 24886954
TI  - Time from admission to initiation of surgery for source control is a critical
      determinant of survival in patients with gastrointestinal perforation with
      associated septic shock.
AB  - INTRODUCTION: We developed a protocol to initiate surgical source control
      immediately after admission (early source control) and perform initial
      resuscitation using early goal-directed therapy (EGDT) for gastrointestinal (GI)
      perforation with associated septic shock. This study evaluated the relationship
      between the time from admission to initiation of surgery and the outcome of the
      protocol. METHODS: This examination is a prospective observational study and
      involved 154 patients of GI perforation with associated septic shock. We
      statistically analyzed the relationship between time to initiation of surgery and
      60-day outcome, examined the change in 60-day outcome associated with each 2 hour
      delay in surgery initiation and determined a target time for 60-day survival.
      RESULTS: Logistic regression analysis demonstrated that time to initiation of
      surgery (hours) was significantly associated with 60-day outcome (Odds ratio
      (OR), 0.31; 95% Confidence intervals (CI)), 0.19-0.45; P <0.0001). Time to
      initiation of surgery (hours) was selected as an independent factor for 60-day
      outcome in multiple logistic regression analysis (OR), 0.29; 95% CI, 0.16-0.47; P
      <0.0001). The survival rate fell as surgery initiation was delayed and was 0% for
      times greater than 6 hours. CONCLUSIONS: For patients of GI perforation with
      associated septic shock, time from admission to initiation of surgery for source
      control is a critical determinant, under the condition of being supported by
      hemodynamic stabilization. The target time for a favorable outcome may be within
      6 hours from admission. We should not delay in initiating EGDT-assisted surgery
      if patients are complicated with septic shock.

PMID- 24886956
TI  - Immunisation with bacterial expressed VP2 and VP5 of bluetongue virus (BTV)
      protect alpha/beta interferon-receptor knock-out (IFNAR(-/-)) mice from
      homologous lethal challenge.
AB  - BTV-4 structural proteins VP2 (as two domains: VP2D1 and VP2D2), VP5 (lacking the
      first 100 amino acids: VP5Delta1-100) and full-length VP7, expressed in bacteria
      as soluble glutathione S-transferase (GST) fusion-proteins, were used to immunise
      Balb/c and alpha/beta interferon receptor knock-out (IFNAR(-/-)) mice.
      Neutralising antibody (NAbs) titres (expressed as log10 of the reciprocal of the
      last dilution of mouse serum which reduced plaque number by >=50%) induced by the
      VP2 domains ranged from 1.806 to 2.408 in Balb/c and IFNAR(-/-) mice. The
      immunised IFNAR(-/-) mice challenged with a homologous live BTV-4 survived and
      failed to develop signs of infection (ocular discharge and apathy). Although
      subsequent attempts to isolate virus were unsuccessful (possibly reflecting
      presence of neutralising antibodies), a transient/low level viraemia was detected
      by real time RT-PCR. In contrast, mice immunised with the two VP2 domains with or
      without VP5Delta1-100 and VP7, then challenged with the heterologous serotype,
      BTV-8, all died by day 7 post-infection. We conclude that immunisation with
      bacterially-expressed VP2 domains can induce strong serotype-specific NAb
      responses. Bacterial expression could represent a cost effective and risk-free
      alternative to the use of live or inactivated vaccines, particularly if viruses
      prove to be difficult to propagate in cell culture (like BTV-25). A vaccine based
      on bacterially expressed VP2 and VP5 of BTV is also DIVA-compatible. 

PMID- 24886957
TI  - Homologous prime boosting based on intranasal delivery of non-pathogenic invasive
      Escherichia coli expressing MPT64, decreases Mycobacterium tuberculosis
      dissemination.
AB  - Protein-subunit vaccines as boosting strategies against tuberculosis (TB)
      infection are currently in the pipeline of TB vaccine research. Their main
      limitation is represented by their poor immunogenicity, which makes it necessary
      to couple protein-subunits with adjuvant molecules. In this study, we employed
      replication-deficient invasive Escherichia coli strains to deliver Mycobacterium
      tuberculosis proteins to the cytoplasm of non-phagocytic eukaryotic cells using
      various priming and prime-boosting vaccination protocols. Our results demonstrate
      that intranasal administration of invasive E. coli expressing the M. tuberculosis
      protective antigen MPT64 to mice primed with a recombinant BCG strain over
      expressing MPT64 on its surface, decrease bacterial burden in mice spleens. Our
      data suggest that replication-deficient invasive E. coli may represent a suitable
      platform for BCG/rBCG priming followed by homologous-boosting immunization
      strategies. 

PMID- 24886958
TI  - Inadequate rabies antibody titers two years after pre-exposure prophylaxis might
      be directly associated with low antibody response to primary vaccine series.

PMID- 24886959
TI  - Identifying human papillomavirus vaccination practices among primary care
      providers of minority, low-income and immigrant patient populations.
AB  - OBJECTIVE: Minority populations in the United States are disproportionally
      affected by human papillomavirus (HPV) infection and HPV-related cancer. We
      sought to understand physician practices, knowledge and beliefs that affect
      utilization of the HPV vaccine in primary care settings serving large minority
      populations in areas with increased rates of HPV-related cancer. STUDY DESIGN:
      Cross-sectional survey of randomly selected primary care providers, including
      pediatricians, family practice physicians and internists, serving large minority
      populations in Brooklyn, N.Y. and in areas with higher than average cervical
      cancer rates. RESULTS: Of 156 physicians randomly selected, 121 eligible
      providers responded to the survey; 64% were pediatricians, 19% were internists
      and 17% were family practitioners. Thirty-four percent of respondents reported
      that they routinely offered HPV vaccine to their eligible patients. Seventy
      percent of physicians reported that the lack of preventive care visits for
      patients in the eligible age group limited their ability to recommend the HPV
      vaccine and 70% of those who reported this barrier do not routinely recommend HPV
      vaccine. The lack of time to educate parents about the HPV vaccine and cost of
      the vaccine to their patients were two commonly reported barriers that affected
      whether providers offered the vaccine. CONCLUSIONS: Our study found that the
      majority of providers serving the highest risk populations for HPV infection and
      HPV-related cancers are not routinely recommending the HPV vaccine to their
      patients. Reasons for providers' failure to recommend the HPV vaccine routinely
      are identified and possible areas for targeted interventions to increase HPV
      vaccination rates are discussed.

PMID- 24886960
TI  - Intervention effects from a social marketing campaign to promote HPV vaccination
      in preteen boys.
AB  - OBJECTIVES: Adoption of human papillomavirus (HPV) vaccination in the US has been
      slow. In 2011, HPV vaccination of boys was recommended by CDC for routine use at
      ages 11-12. We conducted and evaluated a social marketing intervention with
      parents and providers to stimulate HPV vaccination among preteen boys. METHODS:
      We targeted parents and providers of 9-13 year old boys in a 13 county NC region.
      The 3-month intervention included distribution of HPV vaccination posters and
      brochures to all county health departments plus 194 enrolled providers; two radio
      PSAs; and an online CME training. A Cox proportional hazards model was fit using
      NC immunization registry data to examine whether vaccination rates in 9-13 year
      old boys increased during the intervention period in targeted counties compared
      to control counties (n=15) with similar demographics. To compare with other
      adolescent vaccines, similar models were fit for HPV vaccination in girls and
      meningococcal and Tdap vaccination of boys in the same age range. Moderating
      effects of age, race, and Vaccines for Children (VFC) eligibility on the
      intervention were considered. RESULTS: The Cox model showed an intervention
      effect (beta=0.29, HR=1.34, p=.0024), indicating that during the intervention the
      probability of vaccination increased by 34% in the intervention counties relative
      to the control counties. Comparisons with HPV vaccination in girls and Tdap and
      meningococcal vaccination in boys suggest a unique boost for HPV vaccination in
      boys during the intervention. Model covariates of age, race and VFC eligibility
      were all significantly associated with vaccination rates (p<.0001 for all). HPV
      vaccination rates were highest in the 11-12 year old boys. Overall, three of
      every four clinic visits for Tdap and meningococcal vaccines for preteen boys
      were missed opportunities to administer HPV vaccination simultaneously.
      CONCLUSIONS: Social marketing techniques can encourage parents and health care
      providers to vaccinate preteen boys against HPV.

PMID- 24886961
TI  - c-Fos: an AP-1 transcription factor with an additional cytoplasmic, non-genomic
      lipid synthesis activation capacity.
AB  - The mechanisms that co-ordinately activate lipid synthesis when high rates of
      membrane biogenesis are needed to support cell growth are largely unknown. c-Fos,
      a well known AP-1 transcription factor, has emerged as a unique protein with the
      capacity to associate to specific enzymes of the pathway of synthesis of
      phospholipids at the endoplasmic reticulum and activate their synthesis to
      accompany genomic decisions of growth. Herein, we discuss this cytoplasmic, non
      genomic effect of c-Fos in the context of other mechanisms that have been
      proposed to regulate lipid synthesis. 

PMID- 24886963
TI  - Copy number variants in clinical next-generation sequencing data can define the
      relationship between simultaneous tumors in an individual patient.
AB  - Targeted next-generation sequencing (NGS) cancer panels have become a popular
      method for the identification of clinically predictive mutations in cancer. Such
      methods typically detect single nucleotide variants (SNVs) and small
      insertions/deletions (indels) in known cancer genes and can provide further
      information regarding diagnosis in challenging surgical pathology cases, as well
      as identify therapeutic targets and prognostically significant mutations.
      However, in addition to SNVs and indels, other mutation classes, including copy
      number variants (CNVs) and translocations, can be simultaneously detected from
      targeted NGS data. Here, as proof of methods, we present clinical data which
      demonstrate that targeted NGS panels can separate synchronous liver tumors based
      on CNV status, in the absence of distinct SNVs and indels. Such CNV-based
      analysis can be performed without additional cost using existing targeted cancer
      panel data and publically available software. 

PMID- 24886965
TI  - Measurements of isomeric cross sections for the (n,alpha) reaction on the 142Nd
      isotope at approximately 14 MeV neutrons.
AB  - In this study, the activation cross sections were measured for
      (142)Nd(n,alpha)(139m)Ce reaction at four neutron energies between 13.57 and
      14.83 MeV, which were produced by a neutron generator through (3)H((2)H,n)(4)He
      reaction. The production of short-lived activity and the spectra accumulation
      were performed by the cyclic activation technique. Induced gamma-ray activities
      were measured using a high resolution gamma ray spectrometer equipped with a high
      purity Germanium (HpGe) detector. In the cross section measurements, corrections
      were made regarding the effects of the gamma-ray attenuation, the dead-time, the
      fluctuation of the neutron flux, and low energy neutrons. The measured cross
      sections were compared with the published literature and the results of the model
      calculation (TALYS 1.4).

PMID- 24886964
TI  - Performance of a 62Zn/62Cu microgenerator in kit-based synthesis and delivery of
      [62Cu]Cu-ETS for PET perfusion imaging.
AB  - The performance of a commercially produced (62)Zn/(62)Cu microgenerator system,
      and an associated kit-based radiopharmaceutical synthesis method, was evaluated
      for clinical site production of [(62)Cu]Cu-ETS (ethylglyoxal
      bis(thiosemicarbazonato)copper(II)), an investigational agent for PET perfusion
      imaging. Using 37 generators, containing 1.84+/-0.23 GBq (62)Zn at 9:00 AM on the
      day of clinical use, a total of 45 patient doses of [(62)Cu]Cu-ETS (672+/-172
      MBq) were delivered without difficulty. (62)Cu elution yields were high
      (approximately 90%), accompanied by extremely low (62)Zn breakthrough (<0.001%).
      Radiopharmaceutical preparation, from the start-of-elution to time-of-injection,
      consumed less than five minutes. The (62)Zn/(62)Cu microgenerator was a
      dependable source of short-lived positron-emitting (62)Cu, and the kit-based
      synthesis proved to be rapid, robust, and highly reliable for "on-demand"
      delivery of [(62)Cu]Cu-ETS for PET perfusion imaging.

PMID- 24886962
TI  - Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative
      stress and inflammation.
AB  - Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the
      respiratory tract. Evidence suggests that macrophages and inflammatory mediators
      including tumor necrosis factor (TNF)alpha contribute to pulmonary injury.
      Pentoxifylline is a TNFalpha inhibitor known to suppress inflammation. In these
      studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung
      injury and inflammation. Exposure of male Wistar rats (150-174 g; 8-10 weeks) to
      NM (0.125 mg/kg, i.t.) resulted in severe histopathological changes in the lung
      within 3d of exposure, along with increases in bronchoalveolar lavage (BAL) cell
      number and protein, indicating inflammation and alveolar-epithelial barrier
      dysfunction. This was associated with increases in oxidative stress proteins
      including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro
      inflammatory/cytotoxic (COX-2(+) and MMP-9(+)), and anti-inflammatory/wound
      repair (CD163+ and Gal-3(+)) macrophages. Treatment of rats with pentoxifylline
      (46.7 mg/kg, i.p.) daily for 3d beginning 15 min after NM significantly reduced
      NM-induced lung injury, inflammation, and oxidative stress, as measured
      histologically and by decreases in BAL cell and protein content, and levels of HO
      1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after
      pentoxifylline, while CD163+ and Gal-3(+) macrophages increased. This was
      correlated with persistent upregulation of markers of wound repair including pro
      surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM
      induced lung injury and inflammation were associated with alterations in the
      elastic properties of the lung, however these were largely unaltered by
      pentoxifylline. These data suggest that pentoxifylline may be useful in treating
      acute lung injury, inflammation and oxidative stress induced by vesicants.

PMID- 24886966
TI  - Differential effects of sympathetic nervous system and hypothalamic-pituitary
      adrenal axis on systemic immune cells after severe experimental stroke.
AB  - Infectious complications are the leading cause of death in the post-acute phase
      of stroke. Post-stroke immunodeficiency is believed to result from neurohormonal
      dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary
      adrenal (HPA) axis. However, the differential effects of these neuroendocrine
      systems on the peripheral immune cells are only partially understood. Here, we
      determined the impact of the hormones of the SNS and HPA on distinct immune cell
      populations and characterized their interactions after stroke. At various time
      points after cortical or extensive hemispheric cerebral ischemia, plasma
      cortisone, corticosterone, metanephrine and adrenocorticotropic hormone (ACTH)
      levels were measured in mice. Leukocyte subpopulations were flow cytometrically
      analyzed in spleen and blood. To investigate their differential sensitivity to
      stress hormones, splenocytes were incubated in vitro with prednisolone,
      epinephrine and their respective receptor blockers. Glucocorticoid receptor (GCR)
      and beta2-adrenergic receptor (beta2-AR) on leukocyte subpopulations were
      quantified by flow cytometry. In vivo effects of GCR and selective beta2-AR
      blockade, respectively, were defined on serum hormone concentrations, lymphopenia
      and interferon-gamma production after severe ischemia. We found elevated
      cortisone, corticosterone and metanephrine levels and associated lymphocytopenia
      only after extensive brain infarction. Prednisolone resulted in a 5 times higher
      cell death rate of splenocytes than epinephrine in vitro. Prednisolone and
      epinephrine-induced leukocyte cell death was prevented by GCR and beta2-AR
      blockade, respectively. In vivo, only GCR blockade prevented post ischemic
      lymphopenia whereas beta2-AR preserved interferon-gamma secretion by lymphocytes.
      GCR blockade increased metanephrine levels in vivo and prednisolone, in turn,
      decreased beta2-AR expression on lymphocytes. In conclusion, mediators of the SNS
      and the HPA axis differentially affect the systemic immune system after stroke.
      Moreover, our findings suggest a negative-feedback of corticosteroids on the
      sympathetic axis which may control the post-stroke stress-reaction. This complex
      interplay between the HPA and the SNS after stroke has to be considered when
      targeting the neurohormonal systems in the post acute phase of severe stroke. 

PMID- 24886967
TI  - Reduced microglial immunoreactivity for endogenous NMDA receptor agonist
      quinolinic acid in the hippocampus of schizophrenia patients.
AB  - Postmortem and positron emission tomography studies have indicated the
      pathophysiological involvement of microglial cells in schizophrenia. We
      hypothesized that the microglial production of quinolinic acid (QUIN), an
      endogenous N-methyl-d-aspartate receptor (NMDAR) agonist, may be linked to the
      previously described glutamatergic deficits in the hippocampus of schizophrenia
      patients. We performed a semi-quantitative assessment of QUIN-immunoreactive
      microglial cells in schizophrenia patients and matched controls in the CA1,
      CA2/3, and dentate gyrus (DG) area of the posterior hippocampal formation.
      Complementary immunostaining of the commonly used microglial surface marker HLA
      DR was performed in adjacent histological sections. Fewer QUIN-immunoreactive
      microglial cells were observed in the CA1 hippocampal subregion of schizophrenia
      patients compared to controls (left p=0.028, right p=0.018). No significant
      diagnosis-dependent changes were observed in the CA2/3 and DG regions. These
      results were controlled for potential confounds by age, duration of disease,
      autolysis time, psychotropic medication, and hippocampal volume. No diagnosis
      related differences were observed for the overall density of microglial cells
      (HLA-DR expression). Our findings suggest that reduced microglial QUIN content in
      the hippocampal CA1 region is associated with schizophrenia. We hypothesize that
      this association may contribute to impaired glutamatergic neurotransmission in
      the hippocampus of schizophrenia patients. 

PMID- 24886968
TI  - Multiple latent viruses reactivate in astronauts during Space Shuttle missions.
AB  - Latent virus reactivation and diurnal salivary cortisol and
      dehydroepiandrosterone were measured prospectively in 17 astronauts (16 male and
      1 female) before, during, and after short-duration (12-16 days) Space Shuttle
      missions. Blood, urine, and saliva samples were collected during each of these
      phases. Antiviral antibodies and viral load (DNA) were measured for Epstein-Barr
      virus (EBV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). Three
      astronauts did not shed any virus in any of their samples collected before,
      during, or after flight. EBV was shed in the saliva in all of the remaining 14
      astronauts during all 3 phases of flight. Seven of the 14 EBV-shedding subjects
      also shed VZV during and after the flight in their saliva samples, and 8 of 14
      EBV-shedders also shed CMV in their urine samples before, during, and after
      flight. In 6 of 14 crewmembers, all 3 target viruses were shed during one or more
      flight phases. Both EBV and VZV DNA copies were elevated during the flight phase
      relative to preflight or post-flight levels. EBV DNA in peripheral blood was
      increased preflight relative to post-flight. Eighteen healthy controls were also
      included in the study. Approximately 2-5% of controls shed EBV while none shed
      VZV or CMV. Salivary cortisol measured preflight and during flight were elevated
      relative to post-flight. In contrast DHEA decreased during the flight phase
      relative to both preflight and post-flight. As a consequence, the molar ratio of
      the area under the diurnal curve of cortisol to DHEA with respect to ground
      (AUCg) increased significantly during flight. This ratio was unrelated to viral
      shedding. In summary, three herpes viruses can reactivate individually or in
      combination during spaceflight.

PMID- 24886970
TI  - Titanium dioxide nanoparticles as carrier facilitate bioaccumulation of
      phenanthrene in marine bivalve, ark shell (Scapharca subcrenata).
AB  - To evaluate the impact of titanium dioxide nanoparticles (nTiO2) on the uptake of
      hydrophobic organic chemicals by marine bivalves, we conducted a comparative
      bioaccumulation study by exposing clam, Scapharca subcrenata, to phenanthrene
      (Phe) in the presence and absence of nTiO2. The large surface area of nTiO2
      resulted in adsorption of co-existing Phe in aqueous solution to form nTiO2-Phe
      complexes. Accumulation of nTiO2 was not observed in clams at exposed
      concentration (500 MUg/L) in this study. However, enhanced uptake of Phe by clams
      was observed in the presence of nTiO2, with ku and BAFs values being 2 and 1.7
      times higher than that of Phe alone, respectively. The enhanced uptake can be
      explained by ingestion of nTiO2-Phe complexes into the gut and subsequent
      desorption of Phe there. Therefore, nTiO2 as a carrier facilitated the uptake of
      Phe by marine bivalves. 

PMID- 24886969
TI  - DGT-labile As, Cd, Cu and Ni monitoring in freshwater: toward a framework for
      interpretation of in situ deployment.
AB  - The use of the Diffusive Gradient in Thin Film sampler (DGT) as a monitoring tool
      for regulatory programs is currently evaluated. In this context, the impact of
      commonly followed procedures on the accuracy of DGT-labile As, Cd, Cu, and Ni
      quantification was studied. Initial sampler contamination yields to define
      quantification limits instead of using blank subtraction, thus avoiding artifact
      concentrations. Not considering the alteration of element diffusion by the filter
      membrane leads to significant underestimation. However, diffusion coefficients
      determined on a non-fouled membrane were found to be suitable for the studied
      site, making it possible to use data from the literature. When diffusive boundary
      layer formation is neglected, no loss of accuracy is recorded provided the layer
      is thinner than 0.5 mm. Finally, exploration of potential biases allowed
      initiating a framework that might help limit inaccuracies in DGT-labile
      concentration estimation and interpretation, especially in a low contamination
      context. 

PMID- 24886971
TI  - Feasibility of transferring intensive cared preterm infants from incubator to
      open crib at 1600 grams.
AB  - BACKGROUND: Ability to maintain a normal body temperature in an open crib is an
      important physiologic competency generally requested to discharge preterm infants
      from the hospital. The aim of this study is to assess the feasibility of an early
      weaning protocol from incubator in preterm newborns in a Neonatal Intensive Care
      Unit. METHODS: 101 infants with birth weight < 1600 g were included in this
      feasibility study. We compared 80 newborns successfully transferred from an
      incubator to open crib at 1600 g with 21 infants transferred at weight >= 1700 g.
      The primary outcome was to evaluate feasibility of the protocol and the reasons
      for the eventual delay. Secondary outcomes were the identification of factors
      that would increase the likelihood of early weaning, the impact of an earlier
      weaning on discharge timing, and the incidence of adverse outcomes. Newborns in
      the study period were then compared with an historical control group with similar
      characteristics. RESULTS: Early weaning was achieved in 79.2% of infants without
      significant adverse effects on temperature stability or weight gain. Delayed
      weaning was mainly due to the need of respiratory support. Gestational age
      affected the likelihood of early weaning (OR 1.7282 95% CI: 1.3071 - 2.2850). In
      the multivariate linear regression, early weaning reduced length of stay (LOS) by
      25.8 days (p < 0.0001). CONCLUSIONS: Preterm infants can be weaned successfully
      from an incubator to an open crib at weight as low as 1600 grams without
      significant adverse effect. Early weaning significantly reduces LOS in preterm
      newborns.

PMID- 24886972
TI  - Genome-wide analyses of proliferation-important genes of Iridovirus-tiger frog
      virus by RNAi.
AB  - Tiger frog virus (TFV), a species of genus Ranavirus in the family Iridoviridae,
      is a nuclear cytoplasmic large DNA virus that infects aquatic vertebrates such as
      tiger frog (Rana tigrina rugulosa) and Chinese soft-shelled turtle (Trionyx
      sinensis). Based on the available genome sequences of TFV, the well-developed RNA
      interference (RNAi) technique, and the reliable cell line for infection model, we
      decided to analyze the functional importance of all predicted genes. Firstly, a
      relative quantitative cytopathogenic effect (Q-CPE) assay was established to
      monitor the viral proliferation in fish cells. Then, genome-wide RNAi screens of
      95 small interference (si) RNAs against TFV were performed to characterize the
      functional importance of nearly all (95%) predicted TFV genes by Q-CPE scaling
      system. We identified 32 (33.7%) genes as essential, 50 (52.6%) genes as semi
      essential and 13 (13.7%) genes as nonessential for TFV proliferation.
      Quantitative RT-PCR and titer assays of selected genes were performed to verify
      the screen results. Furthermore, the screened essential genes were analyzed for
      their genome distribution and conservative comparison within Ranavirus. Such a
      systematic screen for viral functional genes by cell phenotypes should provide
      further insights into understanding of the information in antiviral targets, and
      in viral replication and pathogenesis of iridovirus. 

PMID- 24886973
TI  - Phosphorylation of serine 349 of p62 in Alzheimer's disease brain.
AB  - BACKGROUND: Extensive research on p62 has established its role in oxidative
      stress, protein degradation and in several diseases such as Paget's disease of
      the bone, frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
      Importantly, previous studies showed that p62 binds directly to Keap1, which is a
      ubiquitin E3 ligase responsible for degrading Nrf2. Indeed, colocalisation of p62
      and Keap1 occurs in tumorigenesis and neurodegeneration. A serine (S) residue in
      the Keap1-interacting region of p62 is phosphorylated in hepatocellular
      carcinoma, and this phosphorylation contributes to tumour growth through the
      higher affinity of p62 to Keap1. However, it remains largely unknown whether p62
      is phosphorylated in the Keap1-interacting region under neurodegenerative
      conditions. RESULTS: To answer this question, we generated an antibody against
      phosphorylated S349 (P-S349) of p62 and showed that S349 is phosphorylated
      following disruption of protein degradation. In particular, the ratio of P-S349
      to total p62 levels was significantly increased in the brains with Alzheimer's
      disease (AD) compared with controls. We also compared the reactivity of the P
      S349 antibody with P-S403 of p62 and showed that these two phosphorylated sites
      on p62 cause different responses with proteasome inhibition and show distinct
      localisation patterns in AD brains. In addition to disruption of protein
      degradation systems, activation of oxidative stress can induce P-S349.
      CONCLUSION: These results support the hypothesis that disruption of protein
      degradation systems and sustained activation of the Keap1-Nrf2 system occur in
      the brains with AD.

PMID- 24886975
TI  - Body mass index and death by stroke: no obesity paradox.
AB  - IMPORTANCE: Reports of an obesity paradox have led to uncertainty about secondary
      prevention in obese patients with stroke. The paradox is disputed and has been
      claimed to be an artifact due to selection bias. OBJECTIVE: To determine whether
      the obesity paradox in stroke is real or an artificial finding due to selection
      bias. DESIGN, SETTING, AND PARTICIPANTS: We studied survival after stroke in
      relation to body mass index (BMI, calculated as weight in kilograms divided by
      height in meters squared). To overcome selection bias, we studied only deaths
      caused by the index stroke on the assumption that death by stroke reported on a
      death certificate was due to the index stroke if death occurred within the first
      month poststroke. We used the Danish Stroke Register, containing information on
      all hospital admissions for stroke in Denmark from 2003 to 2012, and the Danish
      Registry of Causes of Death. The study included all registered Danes (n = 71 617)
      for whom information was available on BMI (n = 53 812), age, sex, civil status,
      stroke severity, stroke subtype, a predefined cardiovascular profile, and
      socioeconomic status. MAIN OUTCOMES AND MEASURES: The independent relation
      between BMI and death by the index stroke within the first week or month by
      calculating hazard ratios in multivariate Cox regression analysis and multiple
      imputation for cases for whom information on BMI was missing. RESULTS: Of the 71
      617 patients, 7878 (11%) had died within the first month; of these, stroke was
      the cause of death of 5512 (70%). Of the patients for whom information on BMI was
      available, 9.7% were underweight, 39.0% were of normal weight, 34.5% were
      overweight, and 16.8% were obese. Body mass index was inversely related to mean
      age at stroke onset (P < .001). There was no difference in the risk for death by
      stroke in the first month among patients who were normal weight (reference),
      overweight (hazard ratio, 0.96; 95% CI, 0.88-1.04), and obese (hazard ratio, 1.0;
      95% CI, 0.88-1.13). Analysis of deaths within 1 week gave similar results.
      CONCLUSIONS AND RELEVANCE: We found no evidence of an obesity paradox in patients
      with stroke. Stroke occurred at a significantly younger age in patients with
      higher BMI. Hence, obese patients with stroke should continue to aim for normal
      weight.

PMID- 24886974
TI  - Transcription factors involved in prostate gland adaptation to androgen
      deprivation.
AB  - Androgens regulate prostate physiology, and exert their effects through the
      androgen receptor. We hypothesized that androgen deprivation needs additional
      transcription factors to orchestrate the changes taking place in the gland after
      castration and for the adaptation of the epithelial cells to the androgen
      deprived environment, ultimately contributing to the origin of castration
      resistant prostate cancer. This study was undertaken to identify transcription
      factors that regulate gene expression after androgen deprivation by castration
      (Cas). For the sake of comparison, we extended the analysis to the effects of
      administration of a high dose of 17beta-estradiol (E2) and a combination of both
      (Cas+E2). We approached this by (i) identifying gene expression profiles and
      enrichment terms, and by searching for transcription factors in the derived
      regulatory pathways; and (ii) by determining the density of putative
      transcription factor binding sites in the proximal promoter of the 10 most up- or
      down-regulated genes in each experimental group in comparison to the controls
      Gapdh and Tbp7. Filtering and validation confirmed the expression and localized
      EVI1 (Mecom), NFY, ELK1, GATA2, MYBL1, MYBL2, and NFkB family members (NFkB1,
      NFkB2, REL, RELA and RELB) in the epithelial and/or stromal cells. These
      transcription factors represent major regulators of epithelial cell survival and
      immaturity as well as an adaptation of the gland as an immune barrier in the
      absence of functional stimulation by androgens. Elk1 was expressed in smooth
      muscle cells and was up-regulated after day 4. Evi1 and Nfy genes are expressed
      in both epithelium and stroma, but were apparently not affected by androgen
      deprivation. 

PMID- 24886977
TI  - Automated analysis of two-dimensional positions and body lengths of earthworms
      (Oligochaeta); MimizuTrack.
AB  - Earthworms are important soil macrofauna inhabiting almost all ecosystems. Their
      biomass is large and their burrowing and ingestion of soils alters soil
      physicochemical properties. Because of their large biomass, earthworms are
      regarded as an indicator of "soil heath". However, primarily because the
      difficulties in quantifying their behavior, the extent of their impact on soil
      material flow dynamics and soil health is poorly understood. Image data, with the
      aid of image processing tools, are a powerful tool in quantifying the movements
      of objects. Image data sets are often very large and time-consuming to analyze,
      especially when continuously recorded and manually processed. We aimed to develop
      a system to quantify earthworm movement from video recordings. Our newly
      developed program successfully tracked the two-dimensional positions of three
      separate parts of the earthworm and simultaneously output the change in its body
      length. From the output data, we calculated the velocity of the earthworm's
      movement. Our program processed the image data three times faster than the manual
      tracking system. To date, there are no existing systems to quantify earthworm
      activity from continuously recorded image data. The system developed in this
      study will reduce input time by a factor of three compared with manual data entry
      and will reduce errors involved in quantifying large data sets. Furthermore, it
      will provide more reliable measured values, although the program is still a
      prototype that needs further testing and improvement. Combined with other
      techniques, such as measuring metabolic gas emissions from earthworm bodies, this
      program could provide continuous observations of earthworm behavior in response
      to environmental variables under laboratory conditions. In the future, this
      standardized method will be applied to other animals, and the quantified
      earthworm movement will be incorporated into models of soil material flow
      dynamics or behavior in response to chemical substances present in the soil. 

PMID- 24886976
TI  - Type 1 regulatory T cells specific for collagen type II as an efficient cell
      based therapy in arthritis.
AB  - INTRODUCTION: Regulatory T (Treg) cells play a crucial role in preventing
      autoimmune diseases and are an ideal target for the development of therapies
      designed to suppress inflammation in an antigen-specific manner. Type 1
      regulatory T (Tr1) cells are defined by their capacity to produce high levels of
      interleukin 10 (IL-10), which contributes to their ability to suppress
      pathological immune responses in several settings. The aim of this study was to
      evaluate the therapeutic potential of collagen type II-specific Tr1 (Col-Treg)
      cells in two models of rheumatoid arthritis (RA) in mice. METHODS: Col-Treg
      clones were isolated and expanded from collagen-specific TCR transgenic mice.
      Their cytokine secretion profile and phenotype characterization were studied. The
      therapeutic potential of Col-Treg cells was evaluated after adoptive transfer in
      collagen-antibody- and collagen-induced arthritis models. The in vivo suppressive
      mechanism of Col-Treg clones on effector T-cell proliferation was also
      investigated. RESULTS: Col-Treg clones are characterized by their specific
      cytokine profile (IL-10(high)IL-4(neg)IFN-gamma(int)) and mediate contact
      independent immune suppression. They also share with natural Tregs high
      expression of GITR, CD39 and granzyme B. A single infusion of Col-Treg cells
      reduced the incidence and clinical symptoms of arthritis in both preventive and
      curative settings, with a significant impact on collagen type II antibodies.
      Importantly, injection of antigen-specific Tr1 cells decreased the proliferation
      of antigen-specific effector T cells in vivo significantly. CONCLUSIONS: Our
      results demonstrate the therapeutic potential of Col-Treg cells in two models of
      RA, providing evidence that Col-Treg could be an efficient cell-based therapy for
      RA patients whose disease is refractory to current treatments.

PMID- 24886979
TI  - Risk factors associated with sporadic salmonellosis in children: a case-control
      study in Lower Saxony, Germany, 2008-2011.
AB  - We conducted a case-control study based on 884 laboratory-confirmed sporadic
      Salmonella cases reported to the German infectious disease notification system.
      For controls, we recruited 510 rotavirus cases via the same system. Univariable
      and multivariable logistic regression analyses were performed separately for
      children aged 0-3 years and 4-14 years. In both age groups, the highest odds
      ratios (OR) were found for raw ground pork consumption [0-3 years: OR 8.6, 95%
      confidence interval (CI) 2.4-30.8; 4-14 years: OR 4.5, 95% CI 1.1-19]. Further
      risk factors were exposure to animals (OR 1.6, 95% CI 1.1-2.1), consumption of
      poultry (OR 1.5, 95% CI 1.1-2.1), food items containing eggs (OR 1.5, 95% CI 1.1
      2) and black pepper (OR 1.7, 95% CI 1.1-3.5) in children aged 0-3 years, and
      consumption of uncooked pork sausage (OR 3.6, 95% CI 1.4-9.3) in children aged 4
      14 years. This study highlights the significance of raw pork products ('Mett' in
      German) as risk factors for sporadic salmonellosis in children in Germany.

PMID- 24886980
TI  - Microarray-based resonance light scattering assay for detecting DNA methylation
      and human DNA methyltransferase simultaneously with high sensitivity.
AB  - A microarray-based resonance light scattering assay, with the combination of
      methylation-sensitive endonuclease and gold nanoparticle (GNP) probes, has been
      proposed to sensitively distinguish the DNA methylation level as low as 0.01% (10
      pM methylated DNA in 100 nM total DNA) and detect human DNA methyltransferase 1
      (Dnmt1) down to 0.1 U mL(-1). 

PMID- 24886978
TI  - Towards user-friendly spelling with an auditory brain-computer interface: the
      CharStreamer paradigm.
AB  - Realizing the decoding of brain signals into control commands, brain-computer
      interfaces (BCI) aim to establish an alternative communication pathway for locked
      in patients. In contrast to most visual BCI approaches which use event-related
      potentials (ERP) of the electroencephalogram, auditory BCI systems are challenged
      with ERP responses, which are less class-discriminant between attended and
      unattended stimuli. Furthermore, these auditory approaches have more complex
      interfaces which imposes a substantial workload on their users. Aiming for a
      maximally user-friendly spelling interface, this study introduces a novel
      auditory paradigm: "CharStreamer". The speller can be used with an instruction as
      simple as "please attend to what you want to spell". The stimuli of CharStreamer
      comprise 30 spoken sounds of letters and actions. As each of them is represented
      by the sound of itself and not by an artificial substitute, it can be selected in
      a one-step procedure. The mental mapping effort (sound stimuli to actions) is
      thus minimized. Usability is further accounted for by an alphabetical stimulus
      presentation: contrary to random presentation orders, the user can foresee the
      presentation time of the target letter sound. Healthy, normal hearing users (n =
      10) of the CharStreamer paradigm displayed ERP responses that systematically
      differed between target and non-target sounds. Class-discriminant features,
      however, varied individually from the typical N1-P2 complex and P3 ERP components
      found in control conditions with random sequences. To fully exploit the
      sequential presentation structure of CharStreamer, novel data analysis approaches
      and classification methods were introduced. The results of online spelling tests
      showed that a competitive spelling speed can be achieved with CharStreamer. With
      respect to user rating, it clearly outperforms a control setup with random
      presentation sequences. 

PMID- 24886981
TI  - Antidepressant and anxiolytic effects of the methanol root extract of Capparis
      thonningii: involvement of monoaminergic, cholinergic and GABAergic systems.
AB  - BACKGROUND: Capparis thonningii Schum. (Capparaceae) is used in traditional
      African Medicine for the treatment of mood disorders. OBJECTIVE: The study
      investigates antidepressant and anxiolytic activities of methanol root extract of
      C. thonningii (CT). METHODS: CT (25-100 mg/kg, p. o.) was administered 1 h before
      behavioral studies were carried out in mice. Antidepressant effect was
      investigated using the forced swimming test (FST) and tail suspension test (TST).
      The anxiolytic effect was evaluated using the elevated-plus maze test (EPM), hole
      board test (HBT), and light-dark test. RESULTS: CT (25 and 50 mg/kg) increased
      swimming activity (P<0.05) by 92.73% and attenuated immobility time by 35.72%,
      similar to anti-immobility effect of imipramine (33.87%) in FST. In addition, CT
      (50 mg/kg) significantly (P<0.01) reduced immobility time by 30.24% in TST. 
      However, the antidepressant-like effect elicited by CT was reversed by
      metergoline, cyproheptadine, and sulpiride (40.81, 45.93, and 48.52%,
      respectively) pretreatment but prazosin, and yohimbine failed to reverse this
      antidepressant-like effect. Similar to diazepam, CT (25 mg/kg) increased duration
      of open arms exploration (P<0.05) by 43.73% in EPM, number of head-dips (HBT)
      (90.32%), and time spent in the light compartment by 45.77% in light/dark test
      indicating anxiolytic-like effect. The anxiolytic-like effect of CT was reversed
      by flumazenil pretreatment. CONCLUSION: The findings from this study suggest
      antidepressant-like effect of C. thonningii involving interaction with
      serotonergic (5-HT2), dopaminergic (D2), noradrenergic (alpha1 and alpha2), and
      muscarinic cholinergic systems; and anxiolytic effect through an interaction with
      GABAA benzodiazepine receptor.

PMID- 24886982
TI  - In vitro infection of human nervous cells by two strains of Toxoplasma gondii: a
      kinetic analysis of immune mediators and parasite multiplication.
AB  - The severity of toxoplasmic infection depends mainly on the immune status of the
      host, but also on the Toxoplasma gondii strains, which differ by their virulence
      profile. The relationship between the human host and T. gondii has not yet been
      elucidated because few studies have been conducted on human models. The immune
      mechanisms involved in the persistence of T. gondii in the brains of
      immunocompetent subjects and during the reactivation of latent infections are
      still unclear. In this study, we analyzed the kinetics of immune mediators in
      human nervous cells in vitro, infected with two strains of T. gondii. Human
      neuroblast cell line (SH SY5Y), microglial (CMH5) and endothelial cells (Hbmec)
      were infected separately by RH (type I) or PRU (type II) strains for 8 h, 14 h,
      24 h and 48 h (ratio 1 cell: 2 tachyzoites). Pro-inflammatory protein expression
      was different between the two strains and among different human nervous cells.
      The cytokines IL-6, IL-8 and the chemokines MCP-1 and GROalpha, and SERPIN E1
      were significantly increased in CMH5 and SH SY5Y at 24 h pi. At this point of
      infection, the parasite burden declined in microglial cells and neurons, but
      remained high in endothelial cells. This differential effect on the early
      parasite multiplication may be correlated with a higher production of immune
      mediators by neurons and microglial cells compared to endothelial cells.
      Regarding strain differences, PRU strain, but not RH strain, stimulates all cells
      to produce pro-inflammatory growth factors, G-CSF and GM-CSF. These proteins
      could increase the inflammatory effect of this type II strain. These results
      suggest that the different protein expression profiles depend on the parasitic
      strain and on the human nervous cell type, and that this could be at the origin
      of diverse brain lesions caused by T. gondii. 

PMID- 24886983
TI  - Dendritic cells utilize the evolutionarily conserved WASH and retromer complexes
      to promote MHCII recycling and helper T cell priming.
AB  - Immature dendritic cells (DCs) maintain a highly dynamic pool of recycling MHCII
      that promotes sampling of environmental antigens for presentation to T helper
      cells. However, the molecular basis of MHCII recycling and the cellular machinery
      that orchestrates MHCII trafficking are incompletely understood. Using a mouse
      model we show that WASH, an actin regulatory protein that facilitates retromer
      function, is essential for MHCII recycling and efficient priming of T helper
      cells. We further demonstrate that WASH deficiency results in impaired MHCII
      surface levels, recycling, and an accumulation of polyubiquitinated MHCII
      complexes, which are subsequently slated for premature lysosomal degradation.
      Consequently, conditional deletion of the Wash gene in DCs impairs priming of
      both conventional and autoimmune T helper cells in vivo and attenuates disease
      progression in a model of experimental autoimmune encephalitis (EAE). Thus, we
      identify a novel mechanism in which DCs employ the evolutionarily conserved WASH
      and retromer complex for MHCII recycling in order to regulate T helper cell
      priming. 

PMID- 24886984
TI  - Ultra-acute increase in blood glucose during prehospital phase is associated with
      worse short-term and long-term survival in ST-elevation myocardial infarction.
AB  - BACKGROUND: The current study was to investigate the blood glucose changes in
      ultra-acute phase in patients with ST-elevation myocardial infarction (STEMI) and
      its associations with patient outcome. METHODS: This study was a retrospective
      population-based observational study utilizing prospectively collected registry
      data complemented with laboratory data. All adult patients with STEMI treated by
      emergency medical services (EMS) in the city of Helsinki from January 2006 to
      December 2010 were included in the study. Both prehospital and hospital admission
      glucose values were available from 152 (32%) of all STEMI patients (n = 469).
      RESULTS: Change in blood glucose from prehospital phase to emergency department
      admission was significantly higher in non-survivors within 30 days compared to
      survivors (+1.2 +/- 5.1 vs. -0.3 +/- 2.4 mmol/l [mean +/- SD], P = 0.03).
      Furthermore, the 3-year survival rate was significantly lower in patients with an
      evident (>=2 mmol/l) rise in blood glucose (P = 0.02). In patients with impaired
      left ventricle function (best ejection fraction < 40%), blood glucose increased
      more compared to patients without it (1.2 +/- 2.9 vs. 0.4 +/- 2.7 mmol/l, P =
      0.01). Increase in glucose was correlated with peak myocardial creatinine kinase
      (r = 0.17, P = 0.04) as a marker of increased size of infarct, but not with
      glycosylated haemoglobin A1C as a marker of chronic hyperglycaemia (r = -0.12, P
      = 0.27). CONCLUSIONS: In patients with STEMI, ultra-acute hyperglycaemia during
      prehospital phase is associated with increased mortality, impaired cardiac
      function and increased size of infarct.

PMID- 24886985
TI  - Biofeedback for treatment of awake and sleep bruxism in adults: systematic review
      protocol.
AB  - BACKGROUND: Bruxism is a disorder of jaw-muscle activity characterised by
      repetitive clenching or grinding of the teeth which results in discomfort and
      damage to dentition. The two clinical manifestations of the condition (sleep and
      awake bruxism) are thought to have unrelated aetiologies but are palliated using
      similar techniques. The lack of a definitive treatment has prompted renewed
      interest in biofeedback, a behaviour change method that uses electronic detection
      to provide a stimulus whenever bruxism occurs. This systematic review aims to
      provide a comprehensive overview of the state of research into biofeedback for
      bruxism; to assess the efficacy and acceptability of biofeedback therapy in
      management of awake bruxism and, separately, sleep bruxism in adults; and to
      compare findings between the two variants. METHODS: A systematic review of
      published literature examining biofeedback as an intervention directed at
      controlling primary bruxism in adults. We will search electronic databases and
      the grey literature using a predefined search strategy to identify randomised and
      non-randomised studies, technical reports and patents. Searches will not be
      restricted by language or date and will be expanded through contact with authors
      and experts, and by following up reference lists and citations. Two authors,
      working independently, will conduct screening of search results, study selection,
      data extraction and quality assessment and a third will resolve any
      disagreements. The primary outcomes of acceptability and effectiveness will be
      assessed using only randomised studies, segregated by bruxism subtype. A meta
      analysis of these data will be conducted only if pre-defined conditions for
      quality and heterogeneity are met, otherwise the data will be summarized in
      narrative form. Data from non-randomised studies will be used to augment a
      narrative synthesis of the state of technical developments and any safety-related
      issues. PROSPERO registration number: CRD42013006880. DISCUSSION: Biofeedback is
      not new, but its place in the clinical management of bruxism remains unclear. New
      research, and the availability of miniaturized consumer-grade devices, makes a
      systematic review timely to guide treatment decisions and inform future research.

PMID- 24886986
TI  - N-terminal tagging of the dopamine transporter impairs protein expression and
      trafficking in vivo.
AB  - The dopamine transporter (DAT) is the primary protein responsible for the uptake
      of dopamine from the extracellular space back into presynaptic neurons. As such,
      it plays an important role in the cessation of dopaminergic neurotransmission and
      in the maintenance of extracellular dopamine homeostasis. Here, we report the
      development of a new BAC transgenic mouse line that expresses DAT with an N
      terminal HA-epitope (HAD-Tg). In this line, two copies of the HA-DAT BAC are
      incorporated into the genome, increasing DAT mRNA levels by 47%. Despite the
      increase in mRNA levels, HAD-Tg mice show no significant increase in the level of
      DAT protein in the striatum, indicating a defect in protein trafficking or
      stability. By crossing HAD-Tg mice with DAT knockout mice (DAT-KO), we engineered
      mice that exclusively express HA-tagged DAT in the absence of endogenous DAT (DAT
      KO/HAD-Tg). We show that DAT-KO/HAD-Tg mice express only 8.5% of WT DAT levels in
      the striatum. Importantly, the HA-tagged DAT that is present in DAT-KO/HAD-Tg
      mice is functional, as it is able to partially rescue the DAT-KO hyperactive
      phenotype. Finally, we provide evidence that the HA-tagged DAT is retained in the
      cell body based on a reduction in the striatum:midbrain protein ratio. These
      results demonstrate that the presence of the N-terminal tag leads to impaired DAT
      protein expression in vivo due in part to improper trafficking of the tagged
      transporter, and highlight the importance of the N-terminus in the transport of
      DAT to striatal terminals.

PMID- 24886988
TI  - CRISPR/Cas9-mediated phage resistance is not impeded by the DNA modifications of
      phage T4.
AB  - Bacteria rely on two known DNA-level defenses against their bacteriophage
      predators: restriction-modification and Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) systems. Certain phages have
      evolved countermeasures that are known to block endonucleases. For example, phage
      T4 not only adds hydroxymethyl groups to all of its cytosines, but also
      glucosylates them, a strategy that defeats almost all restriction enzymes. We
      sought to determine whether these DNA modifications can similarly impede CRISPR
      based defenses. In a bioinformatics search, we found naturally occurring CRISPR
      spacers that potentially target phages known to modify their DNA. Experimentally,
      we show that the Cas9 nuclease from the Type II CRISPR system of Streptococcus
      pyogenes can overcome a variety of DNA modifications in Escherichia coli. The
      levels of Cas9-mediated phage resistance to bacteriophage T4 and the mutant phage
      T4 gt, which contains hydroxymethylated but not glucosylated cytosines, were
      comparable to phages with unmodified cytosines, T7 and the T4-like phage RB49.
      Our results demonstrate that Cas9 is not impeded by N6-methyladenine, 5
      methylcytosine, 5-hydroxymethylated cytosine, or glucosylated 5-hydroxymethylated
      cytosine. 

PMID- 24886987
TI  - Is omega-3 fatty acids enriched nutrition support safe for critical ill patients?
      A systematic review and meta-analysis.
AB  - OBJECTIVE: To systematically review the effects of omega-3 poly unsaturated fatty
      acids (FA) enriched nutrition support on the mortality of critically illness
      patients. METHODS: Databases of Medline, ISI, Cochrane Library, and Chinese
      Biomedicine Database were searched and randomized controlled trials (RCTs) were
      identified. We enrolled RCTs that compared fish oil enriched nutrition support
      and standard nutrition support. Major outcome is mortality. Methodological
      quality assessment was conducted based on Modified Jadad's score scale. For
      control heterogeneity, we developed a method that integrated I2 test, nutritional
      support route subgroup analysis and clinical condition of severity. RevMan 5.0
      software (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for meta
      analysis. RESULTS: Twelve trials involving 1208 patients that met all the
      inclusion criteria. Heterogeneity existed between the trials. A random model was
      used, there was no significant effect on mortality RR, 0.82, 95% confidence
      interval (CI) (0.62, 1.09), p = 0.18. Knowing that the route of fish oil
      administration may affect heterogeneity, we categorized the trials into two sub
      groups: parenteral administration (PN) of omega-3 and enteral administration (EN)
      of omega-3. Six trials administered omega-3 FA through PN. Pooled results
      indicated that omega-3 FA had no significant effect on mortality, RR 0.76, 95% CI
      (0.52, 1.10), p = 0.15. Six trials used omega-3 fatty acids enriched EN. After
      excluded one trial that was identified as source of heterogeneity, pooled data
      indicated omega-3 FA enriched EN significant reduce mortality, RR=0.69, 95% CI
      [0.53, 0.91] (p = 0.007). CONCLUSION: Omega-3 FA enriched nutrition support is
      safe. Due to the limited sample size of the included trials, further large-scale
      RCTs are needed.

PMID- 24886990
TI  - A 10-second fluid challenge guided by transthoracic echocardiography can predict
      fluid responsiveness.
AB  - INTRODUCTION: The accurate assessment of intravascular volume status for the
      therapy of severe hypovolemia and shock is difficult and critical to critically
      ill patients. Non-invasive evaluation of fluid responsiveness by the rapid
      infusion of a very limited amount of volume is an important clinical goal. This
      study aimed to test whether echocardiographic parameters could predict fluid
      responsiveness in critically ill patients following a low-volume (50-ml
      crystalloid solution) infusion over 10 seconds. METHODS: We prospectively studied
      55 mechanically ventilated patients. Echocardiography was performed during a 50
      ml infusion of crystalloid solution over 10 seconds and a further 450 ml over 15
      minutes. Cardiac output (CO), stroke volume (SV), aortic velocity time index
      (VTI), and left ventricular ejection fraction (LVEF) were recorded. Patients were
      classified as responders (Rs) if CO increased by at least 15% following the 500
      ml volume expansion or were classified as non-responders (NRs) if CO increased by
      less than 15%. Area under the receiver operating characteristic curves (AUC)
      compared CO variations after 50 ml over 10 seconds (?CO50) and 500 ml over 15
      minutes (?CO500) and the variation of VTI after infusion of 50 ml of fluid over
      10 seconds (?VTI50). RESULTS: In total, 50 patients were enrolled, and 27 (54%)
      of them were Rs. General characteristics, LVEF, heart rate, and central venous
      pressure were similar between Rs and NRs. In the Rs group, the AUC for ?CO50 was
      0.95 +/- 0.03 (P <0.01; best cutoff value, 6%; sensitivity, 93%; specificity,
      91%). Moreover, ?CO50 and ?CO500 were strongly correlated (r = 0.87; P <0.01).
      The AUC for ?VTI50 was 0.91 +/- 0.04 (P <0.01; best cutoff value, 9%;
      sensitivity, 74%; specificity, 95%). ?VTI50 and ?CO500 were positively correlated
      (r = 0.72; P <0.01). CONCLUSION: In critically ill patients, the variation of CO
      and VTI after the administration of 50-ml crystalloid solution over 10 seconds
      (?CO50 and ?VTI50) can accurately predict fluid responsiveness. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN10524328. Registered 12 December
      2013.

PMID- 24886991
TI  - Psychotropic medications for pediatric functional gastrointestinal disorders.
AB  - We describe the use of psychotropic medications in the treatment of functional
      gastrointestinal disorders (FGIDs) in children based on available data. We
      address their safety and efficacy. Most pediatric gastroenterologists do not or
      are not able to collaborate with child psychiatrists, so it may be beneficial for
      pediatric gastroenterologists to have a working knowledge of off-label
      psychotropic drugs to improve functional symptoms. We recommend that efforts be
      made to involve both the children and their families from the beginning, adverse
      effects be mentioned, and the treatment plan be explained. 

PMID- 24886992
TI  - Spanish national registry of celiac disease: incidence and clinical presentation.
AB  - OBJECTIVES: The aim of this study was to assess the incidence and clinical
      pattern of celiac disease (CD) presently diagnosed in Spanish children. METHODS:
      A prospective, multicenter, nationwide registry of new cases of CD in children
      <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied
      were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional
      status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence
      rate of CD was calculated as new cases per 1000 live births and as new cases per
      100,000 person-years <15 years of age. RESULTS: A total of 974 new cases of CD
      were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses
      occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total
      number of cases in each age group was 385, 409, and 180, respectively. Regarding
      clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical,
      and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651
      children tested positive, respectively, for immunoglobulin A (IgA) anti
      transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti
      gliadin antibodies. Villous atrophy was observed in 92.4% and increased
      intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55%
      had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%,
      DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000
      live births and 54 cases per 100,000 person-years. CONCLUSIONS: In Spain, the
      most frequent clinical presentation of CD is the classical form, mainly diagnosed
      during the first 2 years of life. The observed incidence of CD in Spanish
      children is much higher than the present CD incidence rates observed in other
      European countries.

PMID- 24886993
TI  - Marsupialized fungal mycetoma masquerading as conjunctival melanoma.
AB  - PURPOSE: To report a case of a fungal mass misdiagnosed as a pigmented
      conjunctival melanoma. METHOD: Case report. RESULT: A 38-year-old woman was
      referred for a pigmented conjunctival lesion that was diagnosed as a melanoma.
      She had a history of a scleral buckle in that eye for retinal detachment 2 years
      before presentation. Slit-lamp examination revealed a pigmented mass from the 11-
      to 2-o'clock position. This was noted to be imbricated within the invagination of
      a conjunctival fold from the previous surgery. The mass was removed, cultured,
      and confirmed to be a fungal infection from Scytalidium sp. CONCLUSIONS: Scleral
      buckles can cause folds in the conjunctiva, which can be foci for fungal
      infection.

PMID- 24886995
TI  - Comparison of clinical efficacies of autologous serum eye drops in patients with
      primary and secondary Sjogren syndrome.
AB  - PURPOSE: Autologous serum eye drops are considered to be safe and efficient for
      the treatment of dry eyes associated with Sjogren syndrome (SS). The purpose of
      this study was to compare the clinical efficacies of autologous serum eye drops
      in the management of primary and secondary SS. METHODS: Patients with primary (n
      = 20; 35 eyes) and secondary (n = 14; 27 eyes) SS dry eye were included. Serum
      concentrations of proinflammatory cytokines [tumor necrosis factor alpha,
      interleukin (IL)-1beta, IL-6, and IL-8] were measured by a multiplex immunobead
      assay. The ocular symptom scores, ocular staining grades, and tear break-up time
      were evaluated before and after 4 weeks of 50% autologous serum eye drop
      application. RESULTS: At enrollment, patients with secondary SS had higher serum
      proinflammatory cytokine levels (tumor necrosis factor alpha, IL-1beta, IL-6, and
      IL-8) than patients with primary SS (P < 0.01). After 4 weeks of autologous serum
      eye drop treatment, patients with primary SS had significantly improved ocular
      symptoms (P < 0.01), ocular surface staining grades (P < 0.01), and tear break-up
      time (P < 0.05). However, patients with secondary SS had no improvement (P >
      0.05). CONCLUSIONS: Our results suggest that autologous serum eye drops might not
      be effective for the treatment of secondary SS because of elevated serum
      proinflammatory cytokine levels.

PMID- 24886994
TI  - Fully automated, semiautomated, and manual morphometric analysis of corneal
      subbasal nerve plexus in individuals with and without diabetes.
AB  - PURPOSE: The aim of the study was to determine the association, agreement, and
      detection capability of manual, semiautomated, and fully automated methods of
      corneal nerve fiber length (CNFL) quantification of the human corneal subbasal
      nerve plexus (SNP). METHODS: Thirty-three participants with diabetes and 17
      healthy controls underwent laser scanning corneal confocal microscopy. Eight
      central images of the SNP were selected for each participant and analyzed using
      manual (CCMetrics), semiautomated (NeuronJ), and fully automated (ACCMetrics)
      software to quantify the CNFL. RESULTS: For the entire cohort, mean CNFL values
      quantified by CCMetrics, NeuronJ, and ACCMetrics were 17.4 +/- 4.3 mm/mm, 16.0 +/
      3.9 mm/mm, and 16.5 +/- 3.6 mm/mm, respectively (P < 0.01). CNFL quantified
      using CCMetrics was significantly higher than those obtained by NeuronJ and
      ACCMetrics (P < 0.05). The 3 methods were highly correlated (correlation
      coefficients 0.87-0.98, P < 0.01). The intraclass correlation coefficients were
      0.87 for ACCMetrics versus NeuronJ and 0.86 for ACCMetrics versus CCMetrics.
      Bland-Altman plots showed good agreement between the manual, semiautomated, and
      fully automated analyses of CNFL. A small underestimation of CNFL was observed
      using ACCMetrics with increasing the amount of nerve tissue. All 3 methods were
      able to detect CNFL depletion in diabetic participants (P < 0.05) and in those
      with peripheral neuropathy as defined by the Toronto criteria, compared with
      healthy controls (P < 0.05). CONCLUSIONS: Automated quantification of CNFL
      provides comparable neuropathy detection ability to manual and semiautomated
      methods. Because of its speed, objectivity, and consistency, fully automated
      analysis of CNFL might be advantageous in studies of diabetic neuropathy.

PMID- 24886996
TI  - Air-pulse corneal applanation signal curve parameters for characterization of
      astigmatic corneas.
AB  - PURPOSE: The aim of this study was to test the 42 parameters of the ocular
      response analyzer for distinguishing between the biomechanical properties of
      emmetropic eyes with normal topography and eyes with moderate-to-high with-the
      rule astigmatism (WTA) and against-the-rule astigmatism (ATA) that have symmetric
      bowtie topography. METHODS: This retrospective case series study included 37
      patients (37 studied eyes) with WTA astigmatism and 35 patients (35 studied eyes)
      with ATA astigmatism. The control group consisted of 70 patients with emmetropia
      (70 studied eyes) with normal topography. We first tested correlations of the
      parameters that describe the applanation curve during ocular response analyzer
      measurements with the maximum keratometry values and the corneal thickness in all
      3 groups. We then evaluated the significant parameters among them in search of
      any group differences in the biomechanical properties of the cornea. RESULTS:
      Fifteen parameters correlated with Kmax reading values or corneal thickness
      values. The correlation coefficients (r) were low. The best correlated parameters
      were p1area, p2area, h1, dive1, p2area1, h11, h2, and h21. The ATA group had the
      highest number of parameters (n = 6) with significant differences compared with
      the control group. Only p2area was predictive for ATA. In contrast, the WTA group
      had only 1 parameter (p2area1) that was found to be significantly different
      compared with the control group. CONCLUSIONS: Some of the new waveform parameters
      can distinguish between patients with ATA and WTA and normal topography patterns
      and may delineate the differences in biomechanical properties between these
      groups that may predict the risk of corneal ectasia after laser in situ
      keratomileusis.

PMID- 24886997
TI  - Penetration of silicate nanoparticles into the corneal stroma and intraocular
      fluids.
AB  - PURPOSE: The aim of this study was to investigate transmission of topical
      silicate nanoparticles (SiNPs) through the corneal stroma, anterior chamber, and
      vitreous fluids by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and inductively coupled plasma atomic emission spectrometry
      (ICP-AES), respectively. METHODS: SiNPs with a mean diameter of 40.6 +/- 5.6 nm
      determined by dynamic light scattering were used in this study. The permeability
      of SiNPs was examined across isolated corneal buttons over a 30-minute period. To
      visualize the transport and diffusion of nanoparticles through the corneal
      tissue, SiNPs were applied over the corneal surface and evaluated at 5 and 30
      minutes after SiNPs loading for SEM and 15 minutes for TEM. Sections of 10-MUm
      thickness were cut and visualized using SEM. TEM study was performed on 70- to 90
      nm-thick sections. ICP-AES was used to determine the concentration of SiNPs.
      RESULTS: The determined range of synthesized SiNPs by dynamic light scattering
      was 40 nm (41.9 +/- 5.6 nm). Transmission of SiNPs through the corneal stroma was
      shown successfully with electron microscopic (SEM and TEM) images. The ICP-AES
      results revealed SiNPs in the anterior chamber and vitreous fluid. CONCLUSIONS:
      Topical administration of SiNPs, as a noninvasive, and available modality with
      acceptable penetration through the corneal stroma and deep into the intraocular
      fluids including the anterior chamber and vitreous cavity, may be considered as a
      suitable alternative to invasive intravitreal injection of other expensive
      antineovascularization agents.

PMID- 24886998
TI  - Risk factors for donor endothelial loss in eye bank-prepared posterior lamellar
      corneal tissue for descemet stripping automated endothelial keratoplasty.
AB  - PURPOSE: The aim of this study was to investigate donor, tissue, and precut
      procedure risk factors for endothelial cell density (ECD) loss in posterior
      lamellar corneal tissue preparation by an eye bank for Descemet stripping
      automated endothelial keratoplasty. METHODS: A total of 259 corneoscleral rims
      precut by the Singapore Eye Bank from October 2011 to August 2013 were evaluated.
      Donor characteristics, tissue characteristics, and precut procedure parameters
      were analyzed. RESULTS: The mean donor age was 57.18 +/- 11.35 years, and the
      mean cutting transition time was 4.16 +/- 0.75 seconds. The mean ECD was 2826 +/-
      225 and 2787 +/- 224 cells per square millimeter before and after precutting,
      respectively, with an average ECD change of -1.38% +/- 3.28%. The precutting
      procedure failure rate was 1.2%. Mutivariate regression analysis showed that an
      older donor age, a higher ECD before cutting, and a slower cutting transition
      speed were significant factors. Corneas with an ECD >2800 cells per square
      millimeter before precutting, cutting transition time >5.5 seconds, and corneas
      with donor age >65 years were significantly more likely to have greater than 5%
      ECD loss after precutting (odds ratio, 6.42, 1.66, and 1.62; 95% confidence
      interval, 1.44-29.43, 1.45-2.72, and 1.66-5.82, respectively). Donor source,
      death-to-preservation time (range, 0.67-10.88 hours), death-to-precutting time
      (range, 0-7 days), and graft thickness (range, 43-232 MUm) were not statistically
      significant factors. CONCLUSIONS: The ECD loss in the precut tissue prepared by
      the eye bank was very low. The risk factors identified provide better
      understanding of how to improve the quality and safety profiles when preparing
      graft tissue for Descemet stripping automated endothelial keratoplasty.

PMID- 24887000
TI  - Responses of sap flow, leaf gas exchange and growth of hybrid aspen to elevated
      atmospheric humidity under field conditions.
AB  - An increase in average air temperature and frequency of rain events is predicted
      for higher latitudes by the end of the 21st century, accompanied by a probable
      rise in air humidity. We currently lack knowledge on how forest trees acclimate
      to rising air humidity in temperate climates. We analysed the leaf gas exchange,
      sap flow and growth characteristics of hybrid aspen (Populus tremula * P.
      tremuloides) trees growing at ambient and artificially elevated air humidity in
      an experimental forest plantation situated in the hemiboreal vegetation zone.
      Humidification manipulation did not affect the photosynthetic capacity of plants,
      but did affect stomatal responses: trees growing at elevated air humidity had
      higher stomatal conductance at saturating photosynthetically active radiation (gs
      sat) and lower intrinsic water-use efficiency (IWUE). Reduced stomatal limitation
      of photosynthesis in trees grown at elevated air humidity allowed slightly higher
      net photosynthesis and relative current-year height increments than in trees at
      ambient air humidity. Tree responses suggest a mitigating effect of higher air
      humidity on trees under mild water stress. At the same time, trees at higher air
      humidity demonstrated a reduced sensitivity of IWUE to factors inducing stomatal
      closure and a steeper decline in canopy conductance in response to water deficit,
      implying higher dehydration risk. Despite the mitigating impact of increased air
      humidity under moderate drought, a future rise in atmospheric humidity at high
      latitudes may be disadvantageous for trees during weather extremes and represents
      a potential threat in hemiboreal forest ecosystems. 

PMID- 24887001
TI  - Reprogramming of cassava (Manihot esculenta) microspores towards sporophytic
      development.
AB  - Gametes have the unique potential to enter the sporophytic pathway, called
      androgenesis. The plants produced are usually haploid and recombinant due to the
      preceding meiosis and they can double their chromosome number to form doubled
      haploids, which are completely homozygous. Availability of the doubled haploids
      facilitates mapping the genes of agronomically important traits, shortening the
      time of the breeding process required to produce new hybrids and homozygous
      varieties, and saving the time and cost for inbreeding. This study aimed to test
      the feasibility of using isolated and in vitro cultured immature cassava (Manihot
      esculenta) microspores to reprogramme and initiate sporophytic development.
      Different culture media and different concentrations of two ion components
      (Cu(2+) and Fe(2+)) were tested in two genotypes of cassava. External structural
      changes, nuclear divisions and cellular changes during reprogramming were
      analysed by scanning electron microscopy, by staining with 4',6-diamidino-2
      phenylindole, and through classical histology and transmission electron
      microscopy. In two cassava genotypes, different developmental stages of
      microspores were found to initiate sporophytic cell divisions, that is, with
      tetrads of TMS 60444 and with mid or late uni-nucleate microspores of SM 1219-9.
      In the modified NLN medium (NLNS), microspore enlargements were observed. The
      medium supplemented with either sodium ferrous ethylene-diamine-tetraacetic acid
      (NaFeEDTA) or CuSO4.5H2O induced sporophytic cell division in both genotypes. A
      low frequency of the reprogramming and the presence of non-responsive microspores
      among the responsive ones in tetrads were found to be related to the viability
      and exine formation of the microspores. The present study clearly demonstrated
      that reprogramming occurs much faster in isolated microspore culture than in
      anther culture. This paves the way for the development of an efficient technique
      for the production of homozygous lines in cassava. This is the first ever
      detailed report of microspore reprogramming at the tetrad stage and the first
      report of microspore embryogenesis induction in cassava with detailed evidence. 

PMID- 24886999
TI  - Hyperglycemia-induced diaphragm weakness is mediated by oxidative stress.
AB  - INTRODUCTION: A major consequence of ICU-acquired weakness (ICUAW) is diaphragm
      weakness, which prolongs the duration of mechanical ventilation. Hyperglycemia
      (HG) is a risk factor for ICUAW. However, the mechanisms underlying HG-induced
      respiratory muscle weakness are not known. Excessive reactive oxygen species
      (ROS) injure multiple tissues during HG, but only one study suggests that
      excessive ROS generation may be linked to HG-induced diaphragm weakness. We
      hypothesized that HG-induced diaphragm dysfunction is mediated by excessive
      superoxide generation and that administration of a specific superoxide scavenger,
      polyethylene glycol superoxide dismutase (PEG-SOD), would ameliorate these
      effects. METHODS: HG was induced in rats using streptozotocin (60 mg/kg
      intravenously) and the following groups assessed at two weeks: controls, HG, HG +
      PEG-SOD (2,000U/kg/d intraperitoneally for seven days), and HG + denatured
      (dn)PEG-SOD (2000U/kg/d intraperitoneally for seven days). PEG-SOD and dnPEG-SOD
      were administered on day 8, we measured diaphragm specific force generation in
      muscle strips, force-pCa relationships in single permeabilized fibers,
      contractile protein content and indices of oxidative stress. RESULTS: HG reduced
      diaphragm specific force generation, altered single fiber force-pCa
      relationships, depleted troponin T, and increased oxidative stress. PEG-SOD
      prevented HG-induced reductions in diaphragm specific force generation (for
      example 80 Hz force was 26.4 +/- 0.9, 15.4 +/- 0.9, 24.0 +/- 1.5 and 14.9 +/- 0.9
      N/cm2 for control, HG, HG + PEG-SOD, and HG + dnPEG-SOD groups, respectively, P
      <0.001). PEG-SOD also restored HG-induced reductions in diaphragm single fiber
      force generation (for example, Fmax was 182.9 +/- 1.8, 85.7 +/- 2.0, 148.6 +/-
      2.4 and 90.9 +/- 1.5 kPa in control, HG, HG + PEG-SOD, and HG + dnPEG-SOD groups,
      respectively, P <0.001). HG-induced troponin T depletion, protein nitrotyrosine
      formation, and carbonyl modifications were largely prevented by PEG-SOD.
      CONCLUSIONS: HG-induced reductions in diaphragm force generation occur largely at
      the level of the contractile proteins, are associated with depletion of troponin
      T and increased indices of oxidative stress, findings not previously reported.
      Importantly, administration of PEG-SOD largely ablated these derangements,
      indicating that superoxide generation plays a major role in hyperglycemia-induced
      diaphragm dysfunction. This new mechanistic information could explain how HG
      alters diaphragm function during critical illness.

PMID- 24887002
TI  - Differences in proton pumping and Na/H exchange at the leaf cell tonoplast
      between a halophyte and a glycophyte.
AB  - The tonoplast Na(+)/H(+) antiporter and tonoplast H(+) pumps are essential
      components of salt tolerance in plants. The objective of this study was to
      investigate the transport activity of the tonoplast Na(+)/H(+) antiporter and the
      tonoplast V-H(+)-ATPase and V-H(+)-PPase in a highly tolerant salt-accumulating
      halophyte, Salicornia dolichostachya, and to compare these transport activities
      with activities in the related glycophyte Spinacia oleracea. Vacuolar membrane
      vesicles were isolated by density gradient centrifugation, and the proton
      transport and hydrolytic activity of both H(+) pumps were studied. Furthermore,
      the Na(+)/H(+)-exchange capacity of the vesicles was investigated by 9-amino-6
      chloro-2-methoxyacridine fluorescence. Salt treatment induced V-H(+)-ATPase and V
      H(+)-PPase activity in vesicles derived from S. oleracea, whereas V-H(+)-ATPase
      and V-H(+)-PPase activity in S. dolichostachya was not affected by salt
      treatment. Na(+)/H(+)-exchange capacity followed the same pattern, i.e. induced
      in response to salt treatment (0 and 200 mM NaCl) in S. oleracea and not
      influenced by salt treatment (10 and 200 mM NaCl) in S. dolichostachya. Our
      results suggest that S. dolichostachya already generates a high tonoplast H(+)
      gradient at low external salinities, which is likely to contribute to the high
      cellular salt accumulation of this species at low external salinities. At high
      external salinities, S. dolichostachya showed improved growth compared with S.
      oleracea, but V-H(+)-ATPase, V-H(+)-PPase and Na(+)/H(+)-exchange activities were
      comparable between the species, which might imply that S. dolichostachya more
      efficiently retains Na(+) in the vacuole. 

PMID- 24887003
TI  - Flooding and fragment size interact to determine survival and regrowth after
      fragmentation in two stoloniferous Trifolium species.
AB  - Clonal plants, which reproduce by means of stolons and rhizomes, are common in
      frequently flooded habitats. Resilience to disturbance is an important trait
      enabling plants to survive in such highly disturbed habitats. Resource storage is
      thought to enable clonal plants to resume growth after clonal fragmentation
      caused by disturbance. Here we investigated if submergence prior to disturbance
      reduces survival and regrowth of clonal fragments and whether or not genotypes
      originating from highly disturbed riverine habitats are more resistant to
      mechanical disturbance than genotypes from less disturbed coastal dune slack
      habitats. We further tested if variation in survival and regrowth was affected by
      internode size. Clones from contrasting habitats of two closely related Trifolium
      species were first genotypically characterized by amplification fragment length
      polymorphism and then subjected to soil flooding and subsequent clonal
      fragmentation. These species differ with respect to their abundance in riverine
      and dune slack habitats, with Trifolium repens mainly occurring in riverine
      grasslands and Trifolium fragiferum in coastal dune slacks. Soil flooding
      decreased survival and regrowth by up to 80 %. Plants originating from riverine
      grasslands were less negatively affected by fragmentation than plants from dune
      slack habitats. Surprisingly, ramets did not always benefit from being attached
      to a larger internode, as internode size was often negatively correlated with
      survival after fragmentation. Regrowth, on the other hand, was generally
      positively correlated with internode size. These unexpected results indicate that
      there may be contrasting selection pressures on internode size in stoloniferous
      species growing in severely disturbed habitats. 

PMID- 24887004
TI  - Genome size variation and evolution in allotetraploid Arabidopsis kamchatica and
      its parents, Arabidopsis lyrata and Arabidopsis halleri.
AB  - Polyploidization and subsequent changes in genome size are fundamental processes
      in evolution and diversification. Little is currently known about the extent of
      genome size variation within taxa and the evolutionary forces acting on this
      variation. Arabidopsis kamchatica has been reported to contain both diploid and
      tetraploid individuals. The aim of this study was to determine the genome size of
      A. kamchatica, whether there is variation in ploidy and/or genome size in A.
      kamchatica and to study how genome size has evolved. We used propidium iodide
      flow cytometry to measure 2C DNA content of 73 plants from 25 geographically
      diverse populations of the putative allotetraploid A. kamchatica and its parents,
      Arabidopsis lyrata and Arabidopsis halleri. All A. kamchatica plants appear to be
      tetraploids. The mean 2C DNA content of A. kamchatica was 1.034 pg (1011 Mbp),
      which is slightly smaller than the sum of its diploid parents (A. lyrata: 0.502
      pg; A. halleri: 0.571 pg). Arabidopsis kamchatica appears to have lost ~37.594
      Mbp (3.6 %) of DNA from its 2C genome. Tetraploid A. lyrata from Germany and
      Austria appears to have lost ~70.366 Mbp (7.2 %) of DNA from the 2C genome,
      possibly due to hybridization with A. arenosa, which has a smaller genome than A.
      lyrata. We did find genome size differences among A. kamchatica populations,
      which varied up to 7 %. Arabidopsis kamchatica ssp. kawasakiana from Japan
      appears to have a slightly larger genome than A. kamchatica ssp. kamchatica from
      North America, perhaps due to multiple allopolyploid origins or hybridization
      with A. halleri. However, the among-population coefficient of variation in 2C DNA
      content is lower in A. kamchatica than in other Arabidopsis taxa. Due to its
      close relationship to A. thaliana, A. kamchatica has the potential to be very
      useful in the study of polyploidy and genome evolution. 

PMID- 24887005
TI  - Hydrodynamic alignment and assembly of nanofibrils resulting in strong cellulose
      filaments.
AB  - Cellulose nanofibrils can be obtained from trees and have considerable potential
      as a building block for biobased materials. In order to achieve good properties
      of these materials, the nanostructure must be controlled. Here we present a
      process combining hydrodynamic alignment with a dispersion-gel transition that
      produces homogeneous and smooth filaments from a low-concentration dispersion of
      cellulose nanofibrils in water. The preferential fibril orientation along the
      filament direction can be controlled by the process parameters. The specific
      ultimate strength is considerably higher than previously reported filaments made
      of cellulose nanofibrils. The strength is even in line with the strongest
      cellulose pulp fibres extracted from wood with the same degree of fibril
      alignment. Successful nanoscale alignment before gelation demands a proper
      separation of the timescales involved. Somewhat surprisingly, the device must not
      be too small if this is to be achieved. 

PMID- 24887007
TI  - Sex differences in the neural representation of pain unpleasantness.
AB  - Sex differences in pain perception are still poorly understood, but they may be
      related to the way the brains of men and women respond to the affective
      dimensions of pain. Using a matched pain intensity paradigm, where pain intensity
      was kept constant across participants but pain unpleasantness was left free to
      vary among participants, we studied the relationship between pain unpleasantness
      and pain-evoked brain activity in healthy men and women separately. Experimental
      pain was provoked using transcutaneous electrical stimulation of the sural nerve
      while pain-related brain activity was measured using somatosensory-evoked brain
      potentials with source localization. Cardiac responses to pain were also measured
      using electrocardiac recordings. Results revealed that subjective pain
      unpleasantness was strongly associated with increased perigenual anterior
      cingulate cortex activity in women, whereas it was strongly associated with
      decreased ventromedial prefrontal cortex activity in men. Only ventromedial
      prefrontal cortex deactivations in men were additionally associated with
      increased autonomic cardiac arousal. These results suggest that in order to deal
      with pain's objectionable properties, men preferentially deactivate prefrontal
      suppression regions, leading to the mobilization of threat-control circuits,
      whereas women recruit well-known emotion-processing areas of the brain.
      PERSPECTIVE: This article presents neuroimaging findings demonstrating that
      subjective pain unpleasantness ratings are associated with different pain-evoked
      brain responses in men and women, which has potentially important implications
      regarding sex differences in the risk of developing chronic pain.

PMID- 24887006
TI  - Opioids enhance CXCL1 expression and function after incision in mice.
AB  - Chronic opioid consumption increases postoperative pain. Epigenetic changes
      related to chronic opioid use and surgical incision may be partially responsible
      for this enhancement. The CXCL1/CXCR2 signaling pathway, implicated in several
      pain models, is known to be epigenetically regulated via histone acetylation. The
      current study was designed to investigate the role of CXCL1/CXCR2 signaling in
      opioid-enhanced incisional sensitization and to elucidate the possible epigenetic
      mechanism underlying CXCL1/CXCR2 pathway-mediated regulation of nociceptive
      sensitization in mice. Chronic morphine treatment generated mechanical and
      thermal nociceptive sensitization and also significantly exacerbated incision
      induced mechanical allodynia. Peripheral but not central messenger RNA levels of
      CXCL1 and CXCR2 were increased after incision. The source of peripheral CXCL1
      appeared to be wound area neutrophils. Histone H3 subunit acetylated at the
      lysine 9 position (AcH3K9) was increased in infiltrating dermal neutrophils after
      incision and was further increased in mice with chronic morphine treatment. The
      association of AcH3K9 with the promoter region of CXCL1 was enhanced in mice
      after chronic morphine treatment. The increase in CXCL1 near wounds caused by
      chronic morphine pretreatment was mimicked by pharmacologic inhibition of histone
      deacetylation. Finally, local injection of CXCL1 induced mechanical sensitivity
      in naive mice, whereas blocking CXCR2 reversed mechanical hypersensitivity after
      hind paw incision. PERSPECTIVE: Peripheral CXCL1/CXCR2 signaling helps to control
      nociceptive sensitization after incision, and epigenetic regulation of CXCL1
      expression explains in part opioid-enhanced incisional allodynia in mice. These
      results suggest that targeting CXCL1/CXCR2 signaling may be useful in treating
      nociceptive sensitization, particularly for postoperative pain in chronic opioid
      consuming patients.

PMID- 24887008
TI  - Regulation of nonmuscle myosin II during 3-methylcholanthrene induced
      dedifferentiation of C2C12 myotubes.
AB  - 3-Methylcholanthrene (3MC) induces tumor formation at the site of injection in
      the hind leg of mice within 110 days. Recent reports reveal that the
      transformation of normal muscle cells to atypical cells is one of the causes for
      tumor formation, however the molecular mechanism behind this process is not well
      understood. Here, we show in an in vitro study that 3MC induces fragmentation of
      multinucleate myotubes into viable mononucleates. These mononucleates form
      colonies when they are seeded into soft agar, indicative of cellular
      transformation. Immunoblot analysis reveals that phosphorylation of myosin
      regulatory light chain (RLC20) is 5.6+/-0.5 fold reduced in 3MC treated myotubes
      in comparison to vehicle treated myotubes during the fragmentation of myotubes.
      In contrast, levels of myogenic factors such as MyoD, Myogenin and cell cycle
      regulators such as Cyclin D, Cyclin E1 remain unchanged as assessed by real-time
      PCR array and reverse transcriptase PCR analysis, respectively. Interestingly,
      addition of the myosin light chain kinase inhibitor, ML-7, enhances the
      fragmentation, whereas phosphatase inhibitor perturbs the 3MC induced
      fragmentation of myotubes. These results suggest that decrease in RLC20
      phosphorylation may be associated with the fragmentation step of
      dedifferentiation. 

PMID- 24887010
TI  - Cold priming drives the sub-cellular antioxidant systems to protect
      photosynthetic electron transport against subsequent low temperature stress in
      winter wheat.
AB  - Low temperature seriously depresses the growth of wheat through inhibition of
      photosynthesis, while earlier cold priming may enhance the tolerance of plants to
      subsequent low temperature stress. Here, winter wheat plants were firstly cold
      primed (5.2  degrees C lower temperature than the ambient temperature, viz., 10.0
      degrees C) at the Zadoks growth stage 28 (i.e. re-greening stage, starting on
      20th of March) for 7 d, and after 14 d of recovery the plants were subsequently
      subjected to a 5 d low temperature stress (8.4  degrees C lower than the ambient
      temperature, viz., 14.1  degrees C) at the Zadoks growth stage 31 (i.e. jointing
      stage, starting on 8th April). Compared to the non-primed plants, the cold-primed
      plants possessed more effective oxygen scavenging systems in chloroplasts and
      mitochondria as exemplified by the increased activities of SOD, APX and CAT,
      resulting in a better maintenance in homeostasis of ROS production. The trapped
      energy flux (TRO/CSO) and electron transport (ETO/CSO) in the photosynthetic
      apparatus were found functioning well in the cold-primed plants leading to higher
      photosynthetic rate during the subsequent low temperature stress. Collectively,
      the results indicate that cold priming activated the sub-cellular antioxidant
      systems, depressing the oxidative burst in photosynthetic apparatus, hereby
      enhanced the tolerance to subsequent low temperature stress in winter wheat
      plants. 

PMID- 24887009
TI  - Aquaporin 3 promotes epithelial-mesenchymal transition in gastric cancer.
AB  - BACKGROUND: Gastric carcinoma (GC) is a common and lethal malignancy, and
      epithelial-mesenchymal transition (EMT) is believed to contribute to invasive and
      metastatic tumor growth. Aquaporin 3 (AQP3) is overexpressed in human GC tissues,
      while human epidermal growth factor (EGF) and hepatocyte growth factor, which can
      induce EMT, are able to up-regulate AQP3 expression, subsequently promoting GC
      cell migration and proliferation. The purpose of this study was to investigate
      the effects of AQP3 on EMT in human GC. METHODS: AQP3 and EMT-related proteins
      were detected by immunohistochemistry in human GC specimens and their clinical
      significance evaluated. AQP3 knockdown was attempted using small interfering
      RNAs, while EGF was used to up-regulate AQP3 expression. Western blotting, real
      time quantitative polymerase chain reaction assays and immunofluorescence were
      used to evaluate changes in expression of AQP3 and EMT-related proteins in the
      SGC7901 and MGC803 human GC cell lines. RESULTS: AQP3 up-expression was
      associated with EMT-related proteins in human GC specimens, which correlated with
      poor prognosis for GC. AQP3 modulated GC cell proliferation, migration and
      invasion in vitro, and induced E-cadherin repression. AQP3 also up-regulated the
      expression of vimentin and fibronectin in vitro. The PI3K/AKT/SNAIL signaling
      pathway was likely involved in the induction of EMT by AQP3 in GC. CONCLUSIONS:
      AQP3 promotes EMT in human cases of GC, allowing us to understand the mechanisms
      of AQP3 in GC progression, thus providing a potential strategy for its treatment.

PMID- 24887012
TI  - Determining and broadening the definition of impact from implementing a rational
      priority setting approach in a healthcare organization.
AB  - Techniques to manage scarce healthcare resources continue to evolve in response
      to changing, growing and competing demands. Yet there is no standard definition
      in the priority setting literature of what might constitute the desired impact or
      success of resource management activities. In this 2006-09 study, using action
      research methodology, we determined the impact of implementing a formal priority
      setting model, Program Budgeting and Marginal Analysis (PBMA), in a Canadian
      health authority. Qualitative data were collected through post year-1 (n = 12)
      and year-2 (n = 9) participant interviews, meeting observation and document
      review. Interviews were analyzed using a constant comparison technique to
      identify major themes. Impact can be defined as effects at three levels: system,
      group, and individual. System-level impact can be seen in the actual selection of
      priorities and resource re-allocation. In this case, participants prioritized a
      list of $760,000 worth of investment proposals and $38,000 of disinvestment
      proposals; however, there was no clear evidence as to whether financial resources
      were reallocated as a result. Group and individual impacts, less frequently
      reported in the literature, included changes in priority setting knowledge,
      attitudes and practice. PBMA impacts at these three levels were found to be
      interrelated. This work argues in favor of attempts to expand the definition of
      priority setting success by including both desired system-level outcomes like
      resource re-allocation and individual or group level impacts like changes to
      priority setting knowledge, attitudes and practice. These latter impacts are
      worth pursuing as they appear to be intrinsic to successful system-wide priority
      setting. A broader definition of PBMA impact may also suggest conceptualizing
      PBMA as both a priority setting approach and as a tool to develop individual and
      group priority setting knowledge and practice. These results should be of
      interest to researchers and decision makers using or considering a formal
      priority setting approach to manage scarce healthcare resources. 

PMID- 24887011
TI  - Laparoscopic versus open left colectomy in patients with sigmoid colon cancer:
      prospective cohort study with long-term follow-up.
AB  - BACKGROUND: Laparoscopic left colectomy has obtained a large spread in colon
      surgery for malignant disease despite the need for an adequate learning curve.
      However few studies reported long term data in comparison with open left
      colectomy and most of the authors of large series on colorectal surgery don't
      describe, in subgroup analysis, results obtained in left colonic resections. The
      aim of this study is to report the short and long term follow-up of laparoscopic
      left colon resection in comparison with the open approach, from a single centre,
      performed in the same timeframe. METHODS: Between January 2005 to January 2007,
      55 patients with sigma adenocarcinoma underwent to laparoscopic or open left
      colectomy at the Department of Digestive Surgery, "S. Maria" hospital in Terni -
      Italy. Perioperative and histopathological data and results from oncological
      follow-up, until April 2013, are analyzed. RESULTS: 28 patients underwent
      laparoscopic left colectomy, while 27 patients open left colectomy. Mean hospital
      stay was 8.44 +/- 1.21 in the laparoscopic group versus 6.86 +/- 1.01 in the open
      group. The histopathological analysis shows a mean of 18.13 +/- 6.8 lymph nodes
      removed after laparoscopy and 13.96 +/- 5.72 after open surgery (P = 0.02).
      Kaplan-Meier analysis does not reveal significative differences in disease free
      survival (HR = 0.85; 95% CI = 0.21-3.40; P = 0.81). Overall survival up to 5
      years shows one death per group. CONCLUSIONS: Laparoscopy, respect to the open
      approach, could improve perioperative clinical outcomes, hospital stay and
      harvested lymph nodes with comparable long term oncological follow-up in patients
      with sigmoid colon cancer.

PMID- 24887013
TI  - Plant sterols-enriched diet decreases small, dense LDL-cholesterol levels in
      children with hypercholesterolemia: a prospective study.
AB  - BACKGROUND: Small dense low density lipoprotein-cholesterol (sdLDL-C) molecules
      are more atherogenic compared with large buoyant ones. Phytosterols-enriched
      diets are effective in decreasing total cholesterol (TC) and low density
      lipoprotein-cholesterol (LDL-C) concentrations in hyperlipidemic children without
      significant adverse effects. Limited data on the impact of such a diet on sdLDL-C
      levels is available in adults while there are no reports concerning children. The
      purpose of this study is to prospectively evaluate the effect of the daily
      consumption of 2 g of plant sterols on sdLDL-C levels in children with
      hypercholesterolemia. METHODS: Fifty-nine children, 25 with LDL-C >= 3.4 mmol/l
      (130 mg/dl) and 34 with LDL-C < 3.4 mmol/l, aged 4.5-15.9 years, were included in
      the study. A yogurt-drink enriched with 2 g of plant sterols was added to the
      daily diet of hypercholesterolemic children and 6-12 months later lipid profiles
      were reassessed. Direct quantitative methods were used to measure LDL-C and sdLDL
      C levels. RESULTS: The consumption of plant sterols reduced sdLDL-C significantly
      (p < 0.001), but levels remained higher compared with controls (p < 0.001). TC,
      LDL-C, non high density lipoprotein-cholesterol (NonHDL-C) and apolipoprotein B
      (ApoB) levels also decreased significantly (p < 0.05). The median reduction of
      sdLDL-C and LDL-C was 16.6% and 13%, respectively. These variables decreased >10%
      in sixteen children (64%), independently from baseline levels, sex, age and body
      mass index (BMI). High density lipoprotein-cholesterol (HDL-C), lipoprotein a
      [Lp(a)], and triglycerides (TGs) levels remained unaffected. CONCLUSIONS: Plant
      sterols decrease sdLDL-C significantly and may be beneficial for children with
      hypercholesterolemia.

PMID- 24887014
TI  - Combination of interleukin-12 gene therapy, metronomic cyclophosphamide and DNA
      cancer vaccination directs all arms of the immune system towards tumor
      eradication.
AB  - In this work a combination therapy that acts upon the immune suppressive, the
      innate and specific arms of the immune system is proposed. This combination
      therapy, which consists of intratumoral interleukin-12 (IL-12) gene therapy,
      human tyrosinase (hTyr) DNA vaccination and metronomic cyclophosphamide (CPX),
      was evaluated in a B16-F10 mouse model. The following groups were compared: (1)
      no treatment, (2) control vector, (3) intratumoral IL-12 gene therapy, (4)
      intratumoral IL-12 gene therapy+metronomic CPX, (5) intratumoral IL-12 gene
      therapy+metronomic CPX+hTyr DNA vaccination. Next to clinical efficacy and
      safety, we characterized acute effects of IL-12 and anti-tumor immune response
      after a second tumor challenge. All treatment groups showed increased survival
      and higher cure rates than control groups. Survival of non-cured mice was
      increased when metronomic CPX was combined with IL-12 gene therapy. Furthermore,
      mice that received metronomic CPX had significantly lower percentages of
      regulatory T cells. Addition of the hTyr DNA vaccine increased cure rate and
      resulted in increased survival compared to other treatment groups. We also
      demonstrated that the manifest necrosis within days after IL-12 gene therapy is
      at least partly due to IL-12 mediated activation of NK cells. All cured mice were
      resistant to a second challenge. A humoral memory response against the tumor
      cells was observed in all groups that received IL-12 gene therapy, while a
      cellular memory response was observed only in the vaccinated mice. In conclusion,
      every component of this combination treatment contributed a unique immunologic
      trait with associated clinical benefits. 

PMID- 24887015
TI  - MCS-18, a natural product isolated from Helleborus purpurascens, inhibits
      maturation of dendritic cells in ApoE-deficient mice and prevents early
      atherosclerosis progression.
AB  - INTRODUCTION: Inflammation accelerates both plaque progression and instability in
      the pathogenesis of atherosclerosis. The inhibition of dendritic cell (DC)
      maturation is a promising approach to suppress excessive inflammatory immune
      responses and has been shown to be protective in several autoimmune models. The
      aim of this study was to investigate the immune modulatory effects of the natural
      substance MCS-18, an inhibitor of DC maturation, regarding the progression of
      atherosclerosis in ApoE-deficient mice. MATERIALS AND METHODS: ApoE-deficient
      mice were fed for twelve weeks with a Western-type diet (n = 32) or normal chow
      (control group; n = 16). Animals receiving high-fat diet were treated with MCS-18
      (500 MUg/kg body weight, n = 16) or saline (n = 16) twice a week. After 12 weeks,
      animals were transcardially perfused and sacrificed. The percentage of mature DCs
      (CD3(-)/CD19(-)/CD14(-)/NK1.1(-)/CD11c(+)/MHCII(+)/CD83(+)/CD86(+)) and T cell
      subpopulations (CD4(+)/CD25(+)/Foxp3(+), CD3/CD4/CD8) was analyzed in peripheral
      blood and in the spleen using flow cytometry. Plaque size was determined in the
      aortic root and the thoracoabdominal aorta using en-face staining.
      Immunohistochemical stainings served to detect inflammatory cells in the aortic
      root. Several cytokines and chemokines were determined in serum using multiplex
      assays. RESULTS: In splenic cells derived from saline-treated atherosclerotic
      mice an increased DC maturation, reflected by the upregulation of CD83 and CD86
      expression, was observed. The enhanced expression of both maturation markers was
      absent in MCS-18 treated atherosclerotic mice. While the percentage of splenic
      Foxp3 expressing Treg was increased in animals receiving MCS-18 compared to
      saline-treated atherosclerotic mice, cytotoxic T cells were reduced in the spleen
      and in atherosclerotic lesions of the aortic root. Furthermore, proatherogenic
      cytokines (e.g. IL-6 and IFN-gamma) and chemokines (e.g. MIP-1beta) were
      decreased in serum of MCS-18-treated animals when compared to saline-treated
      atherosclerotic mice. Also plaque size in the aortic root and the
      thoracoabdominal aorta was significantly lower following administration of MCS
      18. CONCLUSION: This study provides for the first time evidence that MCS-18 is
      able to prevent the onset of atherosclerosis in ApoE-deficient mice. The observed
      anti-atherogenic effect is associated with the suppression of DC maturation and
      an inhibited migration and proliferation of cytotoxic T cells.

PMID- 24887016
TI  - Egg consumption and carotid atherosclerosis in the Northern Manhattan study.
AB  - BACKGROUND: The evidence supporting recommendations to limit intake of
      cholesterol rich foods is inconclusive. We aimed to examine the association
      between egg consumption and carotid atherosclerosis phenotypes, and the
      association with clinical vascular events in a prospective, urban, multi-ethnic
      population. METHODS AND RESULTS: The Northern Manhattan Study is a population
      based cohort to determine stroke incidence, risk factors and prognosis. A sub
      cohort of 1429 NOMAS participants with both carotid ultrasounds and comprehensive
      dietary information was evaluated (mean +/- SD age of participants 65.80 +/-
      8.80, 40% male, 18% white, 20% black, 60% Hispanic). The association between egg
      consumption and carotid intima media thickness (cIMT) was assessed with linear
      regression. Logistic and quantile regression was used to examine the association
      between egg consumption and carotid plaque presence, thickness, and area. The
      relation between egg consumption and clinical vascular events (N = 2669) was
      examined with Cox models. The mean total cIMT was 0.91 +/- 0.08 mm and 58% had
      carotid plaque present. Increasing egg consumption was inversely associated with
      cIMT, plaque presence, thickness, and area, in models adjusted for demographics,
      vascular risk factors and diet. For every additional egg consumed per week, the
      risk of plaque decreased by 11% (95% CI 3%-18%). No association was detected
      between egg consumption and risk of clinical vascular outcomes, over a mean
      follow up of 11 years and after adjustment for covariates. CONCLUSIONS: Frequency
      of egg consumption in the low to moderate range was inversely related to several
      markers of carotid atherosclerosis. No association with clinical vascular events,
      including stroke, was detected. Our findings do not support current vascular
      health guidelines suggesting the extreme limitation or avoidance of egg
      consumption due to its cholesterol content.

PMID- 24887017
TI  - Ischemia induces different levels of hypoxia inducible factor-1alpha protein
      expression in interneurons and pyramidal neurons.
AB  - INTRODUCTION: Pyramidal (glutamatergic) neurons and interneurons are
      morphologically and functionally well defined in the central nervous system.
      Although it is known that glutamatergic neurons undergo immediate cell death
      whereas interneurons are insensitive or survive longer during cerebral ischemia,
      the protection mechanisms responsible for this interneuronal survival are not
      well understood. Hypoxia inducible factor-1 (HIF-1) plays an important role in
      protecting neurons from hypoxic/ischemic insults. Here, we studied the expression
      of HIF-1alpha, the regulatable subunit of HIF-1, in the different neuronal
      phenotypes under in vitro and in vivo ischemia. RESULTS: In a primary cortical
      culture, HIF-1alpha expression was observed in neuronal somata after hypoxia (1%
      oxygen) in the presence of 5 or 25 mM glucose but not under normoxia (21%
      oxygen). Interestingly, only certain MAP2-positive neurons containing round
      somata (interneuron-like morphology) co-localized with HIF-1alpha staining. Other
      neurons such as pyramidal-like neurons showed no expression of HIF-1alpha under
      either normoxia or hypoxia. The HIF-1alpha positive neurons were GAD65/67
      positive, confirming that they were interneuron-type cells. The HIF-1alpha
      expressing GAD65/67-positive neurons also possessed high levels of glutathione.
      We further demonstrated that ischemia induced significant HIF-1alpha expression
      in interneurons but not in pyramidal neurons in a rat model of middle cerebral
      artery occlusion. CONCLUSION: These results suggest that HIF-1alpha protein
      expression induced by ischemia is neuron-type specific and that this specificity
      may be related to the intracellular level of glutathione (GSH).

PMID- 24887018
TI  - Effect of 1 night of total sleep deprivation on cerebrospinal fluid beta-amyloid
      42 in healthy middle-aged men: a randomized clinical trial.
AB  - IMPORTANCE: Increasing evidence suggests a relationship between poor sleep and
      the risk of developing Alzheimer disease. A previous study found an effect of
      sleep on beta-amyloid (Abeta), which is a key protein in Alzheimer disease
      pathology. OBJECTIVE: To determine the effect of 1 night of total sleep
      deprivation on cerebrospinal fluid Abeta42 protein levels in healthy middle-aged
      men. DESIGN, SETTING, AND PARTICIPANTS: The Alzheimer, Wakefulness, and Amyloid
      Kinetics (AWAKE) study at the Radboud Alzheimer Center, a randomized clinical
      trial that took place between June 1, 2012, and October 1, 2012. Participants
      were cognitively normal middle-aged men (40-60 years of age) with normal sleep (n
      = 26) recruited from the local population. INTERVENTIONS: Participants were
      randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep
      deprivation (24 hours of wakefulness) (n = 13). MAIN OUTCOMES AND MEASURES: Sleep
      was monitored using continuous polysomnographic recording from 3 pm until 10 am.
      Cerebrospinal fluid samples were collected using an intrathecal catheter at
      defined times to compare cerebral Abeta42 concentrations between evening and
      morning. RESULTS: A night of unrestricted sleep led to a 6% decrease in Abeta42
      levels of 25.3 pg/mL (95% CI [0.94, 49.6], P = .04), whereas sleep deprivation
      counteracted this decrease. When accounting for the individual trajectories of
      Abeta42 over time, a difference of 75.8 pg/mL of Abeta42 was shown between the
      unrestricted sleep and sleep deprivation group (95% CI [3.4, 148.4], P = .04).
      The individual trajectories of evening and morning Abeta42 concentrations
      differed between the unrestricted sleep and sleep deprivation groups (P = .04) in
      contrast to stable Abeta40, tau, and total protein levels. CONCLUSIONS AND
      RELEVANCE: Sleep deprivation, or prolonged wakefulness, interferes with a
      physiological morning decrease in Abeta42. We hypothesize that chronic sleep
      deprivation increases cerebral Abeta42 levels, which elevates the risk of
      Alzheimer disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01194713.

PMID- 24887020
TI  - Uncommon aetiological agents of catheter-related bloodstream infections.
AB  - The clinical and microbiological characteristics of catheter-related bloodstream
      infection (CR-BSI) due to uncommon microorganisms was assessed in a retrospective
      case-control study over a 9-year period in a tertiary teaching hospital. Uncommon
      microorganisms were defined as those representing <0.5% of all CR-BSI. Diagnosis
      of CR-BSI required that the same microorganism was grown from at least one
      peripheral venous blood culture and a catheter tip culture. Thirty-one episodes
      of CR-BSI were identified due to 13 different genera and these accounted for 2.3%
      of all CR-BSI in the hospital. Although these infections were not associated with
      increased mortality, they occurred in patients with more severe underlying
      conditions who were receiving prolonged antibiotic therapy.

PMID- 24887019
TI  - Behcet's disease in HLA-B*51 negative Germans and Turks shows association with
      HLA-Bw4-80I.
AB  - INTRODUCTION: Behcet's disease (BD) as systemic vasculitis of unknown etiology is
      associated with HLA-B*51 in European and Asian populations. HLA-A*26 was claimed
      as an additional BD susceptibility marker in Japanese and Greek patients. This
      study was performed to test for HLA associations in HLA-B*51 negative German and
      Turkish BD populations. METHODS: In total, 65 German and 46 Turkish patients
      lacking HLA-B*51 were analyzed in comparison to healthy HLA-B*51 negative Germans
      (n = 1500) and Turks (n = 130). HLA-A/B genotypes were determined by SSOP. P
      values with correction for multiple testing (p(c)), chi2-test and odds ratio (OR)
      were used for statistical evaluation. RESULTS: HLA-A*26 was significantly more
      frequent in HLA-B*51- German patients [p(c) = 0.0076, OR = 3.23, 95% CI 1.63 to
      6.39] than in respective controls. HLA-A*26 was also elevated in a smaller group
      of Turkish patients versus the controls. Significant association of HLA-Bw4 with
      isoleucine at amino-acid position 80 (HLA-Bw4-80I) was found in the HLA-B*51(-)
      German cohort of BD patients [p(c) = 0.0042, OR = 2.35, 95% CI 1.41 to 3.93) and
      in the Turkish patients in comparison to the respective controls [p = 0.025, OR =
      2.17, 95% CI 1.09 to 4.31]. On the contrary, HLA-Bw4-80 T was reduced in both HLA
      B*51(-) BD patient cohorts. CONCLUSIONS: The study shows a significant
      association of HLA-Bw4-80I present on HLA-B*51 as well as on other B-locus
      molecules with BD. This indicates that distinctive Bw4 epitopes on HLA-B locus
      molecules could play a role in BD pathogenesis. The study also indicates an
      association with HLA-A*26 in German and Turkish BD patients as a genetic risk
      factor independent of HLA-B*51.

PMID- 24887022
TI  - Enhanced recovery after elective open surgical repair of abdominal aortic
      aneurysm: a complementary overview through a pooled analysis of proportions from
      case series studies.
AB  - OBJECTIVES: To evaluate the efficacy and safety of enhanced recovery after
      surgery (ERAS) programs in elective open surgical repair (OSR) of abdominal
      aortic aneurysm (AAA). BACKGROUND: Open surgical repair of AAA is associated with
      high morbidity and mortality, prolonged hospital stay and high costs. ERAS
      programs contribute to the optimization of treatment by reducing hospital stay
      and improving clinical outcomes. METHODS: A review of PubMed, EMBASE and LILACS
      databases was conducted. As only one randomized controlled trial was found, a
      pooled analysis of proportions from case series was conducted, considering it a
      complementary overview of the topic. Inclusion criteria were case series with
      more than five cases reported, adult patients who underwent an elective OSR of
      AAA and use of an ERAS program. ERAS was compared to conventional perioperative
      care. The pooled proportion and the confidence interval (CI) are shown for each
      outcome. The overlap of the CI suggests similar effect of the interventions
      studied. RESULTS: Thirteen case series studies with ERAS involving 1,250 patients
      were compared to six case series with conventional care with a total of 1,429
      patients. The pooled, respective proportions for ERAS and conventional care were:
      mortality, 1.51% [95% CI: 0.0091, 0.0226] and 3.0% [95% CI 0.0183, 0.0445]; and
      incidence of complications, 3.82% [95% CI 0.0259, 0.0528] and 4.0% [95% CI 0.03,
      0.05]. CONCLUSION: This review shows that ERAS and conventional care therapies
      have similar mortality and complication rates in OSR of AAA.

PMID- 24887024
TI  - NMR-based dynamics of free glycosaminoglycans in solution.
AB  - Glycosaminoglycans (GAGs) comprise a special class of complex carbohydrates
      endowed with numerous biological functions. Most of these functions are regulated
      by conformational arrangements or dynamical properties of GAGs in solution.
      Nuclear magnetic resonance (NMR) is a powerful technique used for dynamic
      analyses. Spin relaxation, scalar couplings, chemical shifts and nuclear
      Overhauser effect resonances are the commonest NMR parameters utilized in such
      analyses. Computational molecular dynamics are also very often employed in
      conjunction with, or restrained by, the NMR dataset. This report aims at
      describing the major NMR-based information available so far concerning the
      dynamical properties of free GAGs in solution. 

PMID- 24887021
TI  - The diacylglycerol kinase alpha/atypical PKC/beta1 integrin pathway in SDF-1alpha
      mammary carcinoma invasiveness.
AB  - Diacylglycerol kinase alpha (DGKalpha), by phosphorylating diacylglycerol into
      phosphatidic acid, provides a key signal driving cell migration and matrix
      invasion. We previously demonstrated that in epithelial cells activation of
      DGKalpha activity promotes cytoskeletal remodeling and matrix invasion by
      recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling
      of alpha5beta1 integrin to the tip of pseudopods. In here we investigate the
      signaling pathway by which DGKalpha mediates SDF-1alpha-induced matrix invasion
      of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following
      SDF-1alpha stimulation, DGKalpha is activated and localized at cell protrusion,
      thus promoting their elongation and mediating SDF-1alpha induced MMP-9
      metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by
      DGKalpha promotes localization at cell protrusions of atypical PKCs which play an
      essential role downstream of DGKalpha by promoting Rac-mediated protrusion
      elongation and localized recruitment of beta1 integrin and MMP-9. We finally
      demonstrate that activation of DGKalpha, atypical PKCs signaling and beta1
      integrin are all essential for MDA-MB-231 invasiveness. These data indicates the
      existence of a SDF-1alpha induced DGKalpha - atypical PKC - beta1 integrin
      signaling pathway, which is essential for matrix invasion of carcinoma cells. 

PMID- 24887023
TI  - MUC5AC upstream complex repetitive region length polymorphisms are associated
      with susceptibility and clinical stage of gastric cancer.
AB  - MUC5AC was deemed to be involved in gastric carcinogenesis since aberrant MUC5AC
      expression has been repeatedly detected in patients with gastric cancer (GC). In
      this study, length polymorphisms in a complicated repetitive region adjacent to
      MUC5AC promoter were assessed in 230 patients with GC and 328 cancer-free
      controls. Alleles of 1.4 and 1.8 kb were significantly more prevalent in GC group
      than in controls. In contrast, 2.3 and 2.8 kb alleles occurred at significantly
      lower frequencies in patients than in controls. Alleles were then classified into
      susceptible (S; 1.4 and 1.8 kb), protective (P; 2.3 and 2.8 kb) and null (N; all
      other alleles) categories with respect to their linkage with the susceptibility
      to GC. Individuals with genotype SS had a 2.7-fold increased risk of GC
      occurrence, but PN genotype was associated with a significantly reduced risk of
      this cancer. Moreover, homozygous or heterozygous individuals with one or two
      copies of 1.4 kb allele showed an earlier age of onset and more advanced
      metastasis stage compared with patients without this allele (Bonferroni corrected
      p = 1.35*10(-4) and 6.60*10(-4) accordingly), whereas homozygous patients with
      two copies of 1.8 kb allele were linked to less advanced GC TNM stage. Our
      results suggest that certain genetic variations in MUC5AC upstream repetitive
      region are associated with the susceptibility and progression of GC.

PMID- 24887025
TI  - Metastatic dormancy: a complex network between cancer stem cells and their
      microenvironment.
AB  - Metastasis represents the major threat of cancer progression and generally
      emerges years after the detection of the primary tumor. An important rate
      limiting step resides in cellular dormancy, where a disseminated tumor cell
      remains in a quiescent state at a remote organ. Herein we review the molecular
      mechanisms leading to tumor dormancy, mainly in regards to cellular quiescence
      and the tumor microenvironment. Based on the current published literature, we
      provide evidence that links the cancer stem cell (CSC) theory with dormancy and
      metastasis. Once a disseminated tumor cell reaches a target tissue, a tight
      regulation imposed by the foreign microenvironment will dictate the fate of these
      cells, which implies a balance in the secretion of soluble factors, modulation of
      the extracellular matrix and the angiogenic switch. We investigate thoroughly
      whether the CSC theory could also apply to metastasis initiation. In fact, the
      resistance of CSCs to therapy, leading to the minimal residual disease and
      cellular quiescence phenotypes, predisposes for the development of metastases.
      Finally, we describe the new technologies available for the identification of
      circulating tumor cells (CTCs), as well as their clinical relevance in dormancy
      of metastatic cancer patients.

PMID- 24887026
TI  - Identification of TgCBAP, a novel cytoskeletal protein that localizes to three
      distinct subcompartments of the Toxoplasma gondii pellicle.
AB  - The cytoskeletons of Toxoplasma gondii and related apicomplexan parasites are
      highly polarized, with apical and basal regions comprised of distinct protein
      complexes. Components of these complexes are known to play important roles in
      parasite shape, cell division, and host cell invasion. During an effort to
      discover the biologically relevant target of a small-molecule inhibitor of T.
      gondii invasion (Conoidin A), we discovered a novel cytoskeletal protein that we
      named TgCBAP (Conserved Basal Apical Peripheral protein). Orthologs of TgCBAP are
      only found in the genomes of other apicomplexans; they contain no identifiable
      domains or motifs and their function(s) is unknown. As a first step toward
      elucidating the function of this highly conserved family of proteins, we
      disrupted the TgCBAP gene by double homologous recombination. Parasites lacking
      TgCBAP are as sensitive to the effects of Conoidin A as wild-type parasites,
      demonstrating that TgCBAP is not the biologically relevant target of Conoidin A.
      However, DeltaTgCBAP parasites are significantly shorter than wild-type parasites
      and have a growth defect in culture. Furthermore, TgCBAP has an unusual
      subcellular localization, forming small rings at the apical and basal ends of the
      parasite and localizing to punctate, ring-like structures around the parasite
      periphery. These data identify a new marker of the apical and basal
      subcompartments of T. gondii, reveal a potentially novel compartment along the
      parasite periphery, and identify TgCBAP as a determinant of parasite size that is
      required for a maximally efficient lytic cycle. 

PMID- 24887027
TI  - Socioeconomic differentials in the immediate mortality effects of the national
      Irish smoking ban.
AB  - BACKGROUND: Consistent evidence has demonstrated that smoking ban policies save
      lives, but impacts on health inequalities are uncertain as few studies have
      assessed post-ban effects by socioeconomic status (SES) and findings have been
      inconsistent. The aim of this study was to assess the effects of the national
      Irish smoking ban on ischemic heart disease (IHD), stroke, and chronic
      obstructive pulmonary disease (COPD) mortality by discrete and composite SES
      indicators to determine impacts on inequalities. METHODS: Census data were used
      to assign frequencies of structural and material SES indicators to 34 local
      authorities across Ireland with a 2000-2010 study period. Discrete indicators
      were jointly analysed through principal component analysis to generate a
      composite index, with sensitivity analyses conducted by varying the included
      indicators. Poisson regression with interrupted time-series analysis was
      conducted to examine monthly age and gender-standardised mortality rates in the
      Irish population, ages >=35 years, stratified by tertiles of SES indicators. All
      models were adjusted for time trend, season, influenza, and smoking prevalence.
      RESULTS: Post-ban mortality reductions by structural SES indicators were
      concentrated in the most deprived tertile for all causes of death, while
      reductions by material SES indicators were more equitable across SES tertiles.
      The composite indices mirrored the results of the discrete indicators,
      demonstrating that post-ban mortality decreases were either greater or similar in
      the most deprived when compared to the least deprived for all causes of death.
      CONCLUSIONS: Overall findings indicated that the national Irish smoking ban
      reduced inequalities in smoking-related mortality. Due to the higher rates of
      smoking-related mortality in the most deprived group, even equitable reductions
      across SES tertiles resulted in decreases in inequalities. The choice of SES
      indicator was influential in the measurement of effects, underscoring that a
      differentiated analytical approach aided in understanding the complexities in
      which structural and material factors influence mortality.

PMID- 24887028
TI  - The therapeutic potential of C-peptide in kidney disease: a protocol for a
      systematic review and meta-analysis.
AB  - BACKGROUND: Kidney disease remains a major cause of morbidity and mortality in
      Canada and worldwide. New medical treatments are needed to reduce the progression
      of kidney disease to improve patient outcomes. C-peptide is normally released by
      pancreatic beta-cells along with insulin in healthy individuals, and has been
      shown to have intrinsic biological activity and to potentially be renoprotective.
      The effect of exogenous C-peptide on kidney structure and function, and the role
      of C-peptide in the treatment of kidney disease have not yet been fully
      elucidated. METHODS/DESIGN: We will conduct a systematic review of the literature
      in human clinical trials and mammalian experimental models to ascertain the
      current evidence for the role of C-peptide as a potential therapeutic agent for
      the treatment of kidney disease. We aim to identify whether exogenously delivered
      C-peptide has an effect on clinically relevant outcomes such as glomerular
      filtration rate, proteinuria, kidney histology, requirement of renal replacement
      therapy, and mortality. We will search MEDLINE, EMBASE, and the Cochrane Central
      Databases for human or animal studies in which C-peptide was administered and
      renal endpoints were subsequently measured. Study quality will be assessed using
      the Cochrane Collaboration's tool for assessing risk of bias. If appropriate, a
      meta-analysis will be performed as per standard techniques. DISCUSSION: The
      results of this study will determine the potential role of C-peptide as a
      therapeutic intervention for patients with kidney disease and will help guide
      subsequent clinical trials. The study may also provide insight into which
      patients or disease states are likely to benefit the most from C-peptide.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014007472.

PMID- 24887029
TI  - Patterns of variation at Ustilago maydis virulence clusters 2A and 19A largely
      reflect the demographic history of its populations.
AB  - The maintenance of an intimate interaction between plant-biotrophic fungi and
      their hosts over evolutionary times involves strong selection and adaptative
      evolution of virulence-related genes. The highly specialised maize pathogen
      Ustilago maydis is assigned with a high evolutionary capability to overcome host
      resistances due to its high rates of sexual recombination, large population sizes
      and long distance dispersal. Unlike most studied fungus-plant interactions, the
      U. maydis - Zea mays pathosystem lacks a typical gene-for-gene interaction. It
      exerts a large set of secreted fungal virulence factors that are mostly organised
      in gene clusters. Their contribution to virulence has been experimentally
      demonstrated but their genetic diversity within U. maydis remains poorly
      understood. Here, we report on the intraspecific diversity of 34 potential
      virulence factor genes of U. maydis. We analysed their sequence polymorphisms in
      17 isolates of U. maydis from Europe, North and Latin America. We focused on gene
      cluster 2A, associated with virulence attenuation, cluster 19A that is crucial
      for virulence, and the cluster-independent effector gene pep1. Although higher
      compared to four house-keeping genes, the overall levels of intraspecific genetic
      variation of virulence clusters 2A and 19A, and pep1 are remarkably low and
      commensurate to the levels of 14 studied non-virulence genes. In addition, each
      gene is present in all studied isolates and synteny in cluster 2A is conserved.
      Furthermore, 7 out of 34 virulence genes contain either no polymorphisms or only
      synonymous substitutions among all isolates. However, genetic variation of
      clusters 2A and 19A each resolve the large scale population structure of U.
      maydis indicating subpopulations with decreased gene flow. Hence, the genetic
      diversity of these virulence-related genes largely reflect the demographic
      history of U. maydis populations. 

PMID- 24887031
TI  - A ciliopathy with hydrocephalus, isolated craniosynostosis, hypertelorism, and
      clefting caused by deletion of Kif3a.
AB  - Malformations of the facial midline are a consistent feature among individuals
      with defects in primary cilia. Here, we provide a framework in which to consider
      how these primary cilia-dependent facial anomalies occur. We generated mice in
      which the intraflagellar transport protein Kif3a was deleted in cranial neural
      crest cells. The Kif3a phenotypes included isolated metopic craniosynostosis,
      delayed closure of the anterior fontanelles, and hydrocephalus, as well as
      midline facial anomalies including hypertelorism, cleft palate, and bifid nasal
      septum. Although all cranial neural crest cells had truncated primary cilia as a
      result of the conditional deletion, only those in the midline showed evidence of
      hyper-proliferation and ectopic Wnt responsiveness. Thus, cranial neural crest
      cells do not rely on primary cilia for their migration but once established in
      the facial prominences, midline cranial neural crest cells require Kif3a function
      in order to integrate and respond to Wnt signals from the surrounding epithelia. 

PMID- 24887033
TI  - The use of optical imaging to assess the potential for embryo-fetal exposure to
      an exogenous material after intravaginal administration.
AB  - A beta-actin-luc transgenic mouse model was used to evaluate whether embryo-fetal
      exposure could occur after intravaginal administration of a compound. A
      bioluminescent substrate, d-luciferin, was delivered intravaginally to mimic
      compound exposure to the female reproductive track and the embryo-fetus.
      Bioluminescence was observed throughout the reproductive tract during diestrus,
      but not during estrus, 2-5min after intravaginal d-luciferin administration to
      female beta-actin-luc mice. Intravaginal administration of d-luciferin to wild
      type females mated with male beta-actin-luc mice indicated that the substrate
      reached the developing embryo-fetus, with bioluminescence corresponding to
      transgene expression in the embryo-fetus. d-Luciferin substrate rapidly reached
      the embryo-fetus regardless of the administration route (intravaginal,
      intraperitoneal, subcutaneous, or intravenous). Vaginal ligation appeared to
      block at least some direct exposure to the embryo-fetus, but did not prevent d
      luciferin from eventually reaching the embryo-fetus. Additional work will be
      necessary to form the basis for a reliable assessment of the human risk for male
      mediated teratogenicity. 

PMID- 24887032
TI  - Novel molecular events associated with altered steroidogenesis induced by
      exposure to atrazine in the intact and castrate male rat.
AB  - Toxicology is increasingly focused on molecular events comprising adverse outcome
      pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but
      relationships to gonadal alterations are unknown. We characterized hormone
      profiles and adrenal (intact and castrate) and testis (intact) proteomes in rats
      after 3 days of exposure. The adrenal accounted for most of the serum
      progesterone and all of the corticosterone increases in intact and castrated
      males. Serum luteinizing hormone, androstenedione, and testosterone in intact
      males shared a non-monotonic response suggesting transition from an acute
      stimulatory to a latent inhibitory response to exposure. Eight adrenal proteins
      were significantly altered with dose. There were unique proteomic changes between
      the adrenals of intact and castrated males. Six testis proteins in intact males
      had non-monotonic responses that significantly correlated with serum
      testosterone. Different dose-response curves for steroids and proteins in the
      adrenal and testis reveal novel adverse outcome pathways in intact and castrated
      male rats. 

PMID- 24887034
TI  - The effect of prone positioning on mortality in patients with acute respiratory
      distress syndrome: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: Prone positioning (PP) has been reported to improve the survival of
      patients with severe acute respiratory distress syndrome (ARDS). However, it is
      uncertain whether the beneficial effects of PP are associated with positive end
      expiratory pressure (PEEP) levels and long durations of PP. In this meta
      analysis, we aimed to evaluate whether the effects of PP on mortality could be
      affected by PEEP level and PP duration and to identify which patients might
      benefit the most from PP. METHODS: Publications describing randomized controlled
      trials (RCTs) in which investigators have compared prone and supine ventilation
      were retrieved by searching the following electronic databases: PubMed/MEDLINE,
      the Cochrane Library, the Web of Science and Elsevier Science (inception to May
      2013). Two investigators independently selected RCTs and assessed their quality.
      The data extracted from the RCTs were combined in a cumulative meta-analysis and
      analyzed using methods recommended by the Cochrane Collaboration. RESULTS: A
      total of nine RCTs with an aggregate of 2,242 patients were included. All of the
      studies received scores of up to three points using the methods recommended by
      Jadad et al. One trial did not conceal allocation. This meta-analysis revealed
      that, compared with supine positioning, PP decreased the 28- to 30-day mortality
      of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of
      inspired oxygen <= 100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence
      interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day
      mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day
      mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS
      patients ventilated with PEEP >= 10 cmH2O. Moreover, PP reduced 28- to 30-day
      mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54
      to 0.99; P = 0.04). CONCLUSIONS: PP reduced mortality among patients with severe
      ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP
      improved the survival of ARDS patients.

PMID- 24887036
TI  - High density lipoprotein from patients with valvular heart disease uncouples
      endothelial nitric oxide synthase.
AB  - Normal high density lipoprotein (HDL) protects vascular function; however these
      protective effects of HDL may absent in valvular heart disease (VHD). Because
      vascular function plays an important role in maintaining the circulation post
      cardiac surgery and some patients are difficult to stabilize, we hypothesized
      that a deleterious vascular effect of HDL may contribute to vascular dysfunction
      in VHD patients following surgery. HDL was isolated from age-match 28 healthy
      subjects and 84 patients with VHD and during cardiac surgery. HDL pro
      inflammation index was measured and the effects of HDL on vasodilation, protein
      interaction, generation of nitric oxide (NO) and superoxide were determined.
      Patients with VHD received either simvastatin (20mg/d) or routine medications,
      and endothelial effects of HDL were characterized. HDL inflammation index
      significantly increased in VHD patients and post-cardiac surgery. HDL from VHD
      patients and post-cardiac surgery significantly impaired endothelium-dependent
      vasodilation, inhibited both Akt and endothelial nitric oxide synthase (eNOS)
      phosphorylation at S1177, eNOS associated with heat shock protein 90 (HSP90), NO
      production and increased eNOS phosphorylation at T495 and superoxide generation.
      Simvastatin therapy partially reduced HDL inflammation index, improved the
      capacity of HDL to stimulate eNOS and Akt phosphorylation at S1177, eNOS
      associated with HSP90, NO production, reduced eNOS phosphorylation at T495 and
      superoxide generation, and improved endothelium-dependent vasodilation. Our data
      demonstrated that HDL from VHD patients and cardiac surgery contributed to
      endothelial dysfunction through uncoupling of eNOS. This deleterious effect can
      be reversed by simvastatin, which improves the vasoprotective effects of HDL.
      Targeting HDL may be a therapeutic strategy for maintaining vascular function and
      improving the outcomes post-cardiac surgery. 

PMID- 24887037
TI  - Effectiveness of a simplified cardiopulmonary resuscitation training program for
      the non-medical staff of a university hospital.
AB  - BACKGROUND: The 2010 Consensus on Science and Treatment Recommendations Statement
      recommended that short video/computer self-instruction courses, with minimal or
      no instructor coaching, combined with hands-on practice can be considered an
      effective alternative to instructor-led basic life support courses. The purpose
      of this study was to examine the effectiveness of a simplified cardiopulmonary
      resuscitation (CPR) training program for non-medical staff working at a
      university hospital. METHODS: Before and immediately after a 45-min CPR training
      program consisting of instruction on chest compression and automated external
      defibrillator (AED) use with a personal training manikin, CPR skills were
      automatically recorded and evaluated. Participants' attitudes towards CPR were
      evaluated by a questionnaire survey. RESULTS: From September 2011 through March
      2013, 161 participants attended the program. We evaluated chest compression
      technique in 109 of these participants. The number of chest compressions
      delivered after the program versus that before was significantly greater (110.8
      +/- 13.0/min vs 94.2 +/- 27.4/min, p < 0.0001), interruption of chest
      compressions was significantly shorter (0.05 +/- 0.34 sec/30 sec vs 0.89 +/- 3.52
      sec/30 sec, p < 0.05), mean depth of chest compressions was significantly greater
      (57.6 +/- 6.8 mm vs 52.2 +/- 9.4 mm, p < 0.0001), and the proportion of
      incomplete chest compressions of <5 cm among all chest compressions was
      significantly decreased (8.9 +/- 23.2% vs 38.6 +/- 42.9%, p < 0.0001). Of the 159
      participants who responded to the questionnaire survey after the program, the
      proportion of participants who answered 'I can check for a response,' 'I can
      perform chest compressions,' and 'I can absolutely or I think I can use an AED'
      increased versus that before the program (81.8% vs 19.5%, 77.4% vs 10.1%, 84.3%
      vs 23.3%, respectively). CONCLUSIONS: A 45-min simplified CPR training program on
      chest compression and AED use improved CPR quality and the attitude towards CPR
      and AED use of non-medical staff of a university hospital.

PMID- 24887038
TI  - Robust sensing of approaching vehicles relying on acoustic cues.
AB  - The latest developments in automobile design have allowed them to be equipped
      with various sensing devices. Multiple sensors such as cameras and radar systems
      can be simultaneously used for active safety systems in order to overcome blind
      spots of individual sensors. This paper proposes a novel sensing technique for
      catching up and tracking an approaching vehicle relying on an acoustic cue.
      First, it is necessary to extract a robust spatial feature from noisy acoustical
      observations. In this paper, the spatio-temporal gradient method is employed for
      the feature extraction. Then, the spatial feature is filtered out through
      sequential state estimation. A particle filter is employed to cope with a highly
      non-linear problem. Feasibility of the proposed method has been confirmed with
      real acoustical observations, which are obtained by microphones outside a
      cruising vehicle. 

PMID- 24887039
TI  - Novel algorithm for identifying and fusing conflicting data in wireless sensor
      networks.
AB  - There is continuously increasing interest in research on multi-sensor data fusion
      technology. Because Dempster's rule of combination can be problematic when
      dealing with conflicting data, there are numerous issues that make data fusion a
      challenging task, including the exponential explosion, Zadeh Paradox, and one
      vote veto. These issues lead to a great difference between the fusion results and
      real results. This paper applies the idea of analyzing distance-based evidence
      conflicts, introduces the concept of vector space, and proposes a new cosine
      theorem-based method of identifying and expressing conflicting data. In addition,
      this paper proposes a new data fusion algorithm based on the degree of mutual
      support between beliefs, which is based on the Jousselme distance-based
      combination rule proposed by Deng et al. Simulation results demonstrate that the
      presented algorithm achieves great improvements in both the accuracy of
      identifying conflicting data and that of fusing conflicting data. 

PMID- 24887040
TI  - How can we tackle energy efficiency in IoT based smart buildings?
AB  - Nowadays, buildings are increasingly expected to meet higher and more complex
      performance requirements. Among these requirements, energy efficiency is
      recognized as an international goal to promote energy sustainability of the
      planet. Different approaches have been adopted to address this goal, the most
      recent relating consumption patterns with human occupancy. In this work, we
      analyze what are the main parameters that should be considered to be included in
      any building energy management. The goal of this analysis is to help designers to
      select the most relevant parameters to control the energy consumption of
      buildings according to their context, selecting them as input data of the
      management system. Following this approach, we select three reference smart
      buildings with different contexts, and where our automation platform for energy
      monitoring is deployed. We carry out some experiments in these buildings to
      demonstrate the influence of the parameters identified as relevant in the energy
      consumption of the buildings. Then, in two of these buildings are applied
      different control strategies to save electrical energy. We describe the
      experiments performed and analyze the results. The first stages of this
      evaluation have already resulted in energy savings of about 23% in a real
      scenario. 

PMID- 24887041
TI  - A novel micro- and nano-scale positioning sensor based on radio frequency
      resonant cavities.
AB  - In many micro- and nano-scale technological applications high sensitivity
      displacement sensors are needed, especially in ultraprecision metrology and
      manufacturing. In this work a new way of sensing displacement based on radio
      frequency resonant cavities is presented and experimentally demonstrated using a
      first laboratory prototype. The principle of operation of the new transducer is
      summarized and tested. Furthermore, an electronic interface that can be used
      together with the displacement transducer is designed and proved. It has been
      experimentally demonstrated that very high and linear sensitivity characteristic
      curves, in the range of some kHz/nm; are easily obtainable using this kind of
      transducer when it is combined with a laboratory network analyzer. In order to
      replace a network analyzer and provide a more affordable, self-contained, compact
      solution, an electronic interface has been designed, preserving as much as
      possible the excellent performance of the transducer, and turning it into a true
      standalone positioning sensor. The results obtained using the transducer together
      with a first prototype of the electronic interface built with cheap discrete
      elements show that positioning accuracies in the micrometer range are obtainable
      using this cost-effective solution. Better accuracies would also be attainable
      but using more involved and costly electronics interfaces. 

PMID- 24887043
TI  - Precise calibration of a GNSS antenna array for adaptive beamforming
      applications.
AB  - The use of global navigation satellite system (GNSS) antenna arrays for
      applications such as interference counter-measure, attitude determination and
      signal-to-noise ratio (SNR) enhancement is attracting significant attention.
      However, precise antenna array calibration remains a major challenge. This paper
      proposes a new method for calibrating a GNSS antenna array using live signals and
      an inertial measurement unit (IMU). Moreover, a second method that employs the
      calibration results for the estimation of steering vectors is also proposed.
      These two methods are applied to the receiver in two modes, namely calibration
      and operation. In the calibration mode, a two-stage optimization for precise
      calibration is used; in the first stage, constant uncertainties are estimated
      while in the second stage, the dependency of each antenna element gain and phase
      patterns to the received signal direction of arrival (DOA) is considered for
      refined calibration. In the operation mode, a low-complexity iterative and fast
      converging method is applied to estimate the satellite signal steering vectors
      using the calibration results. This makes the technique suitable for real-time
      applications employing a precisely calibrated antenna array. The proposed
      calibration method is applied to GPS signals to verify its applicability and
      assess its performance. Furthermore, the data set is used to evaluate the
      proposed iterative method in the receiver operation mode for two different
      applications, namely attitude determination and SNR enhancement. 

PMID- 24887042
TI  - Context representation and fusion: advancements and opportunities.
AB  - The acceptance and usability of context-aware systems have given them the edge of
      wide use in various domains and has also attracted the attention of researchers
      in the area of context-aware computing. Making user context information available
      to such systems is the center of attention. However, there is very little
      emphasis given to the process of context representation and context fusion which
      are integral parts of context-aware systems. Context representation and fusion
      facilitate in recognizing the dependency/relationship of one data source on
      another to extract a better understanding of user context. The problem is more
      critical when data is emerging from heterogeneous sources of diverse nature like
      sensors, user profiles, and social interactions and also at different timestamps.
      Both the processes of context representation and fusion are followed in one way
      or another; however, they are not discussed explicitly for the realization of
      context-aware systems. In other words most of the context-aware systems
      underestimate the importance context representation and fusion. This research has
      explicitly focused on the importance of both the processes of context
      representation and fusion and has streamlined their existence in the overall
      architecture of context-aware systems' design and development. Various
      applications of context representation and fusion in context-aware systems are
      also highlighted in this research. A detailed review on both the processes is
      provided in this research with their applications. Future research directions
      (challenges) are also highlighted which needs proper attention for the purpose of
      achieving the goal of realizing context-aware systems. 

PMID- 24887044
TI  - Multimodal wireless sensor network-based ambient assisted living in real homes
      with multiple residents.
AB  - Human activity recognition and behavior monitoring in a home setting using
      wireless sensor networks (WSNs) provide a great potential for ambient assisted
      living (AAL) applications, ranging from health and wellbeing monitoring to
      resource consumption monitoring. However, due to the limitations of the sensor
      devices, challenges in wireless communication and the challenges in processing
      large amounts of sensor data in order to recognize complex human activities, WSN
      based AAL systems are not effectively integrated in the home environment.
      Additionally, given the variety of sensor types and activities, selecting the
      most suitable set of sensors in the deployment is an important task. In order to
      investigate and propose solutions to such challenges, we introduce a WSN-based
      multimodal AAL system compatible for homes with multiple residents. Particularly,
      we focus on the details of the system architecture, including the challenges of
      sensor selection, deployment, networking and data collection and provide
      guidelines for the design and deployment of an effective AAL system. We also
      present the details of the field study we conducted, using the systems deployed
      in two different real home environments with multiple residents. With these
      systems, we are able to collect ambient sensor data from multiple homes. This
      data can be used to assess the wellbeing of the residents and identify deviations
      from everyday routines, which may be indicators of health problems. Finally, in
      order to elaborate on the possible applications of the proposed AAL system and to
      exemplify directions for processing the collected data, we provide the results of
      several human activity inference experiments, along with examples on how such
      results could be interpreted. We believe that the experiences shared in this work
      will contribute towards accelerating the acceptance of WSN-based AAL systems in
      the home setting. 

PMID- 24887045
TI  - Analysis of benzo[a]pyrene in vegetable oils using molecularly imprinted solid
      phase extraction (MISPE) coupled with enzyme-linked immunosorbent assay (ELISA).
AB  - This paper describes the development of a molecularly imprinted polymer-based
      solid phase extraction (MISPE) method coupled with enzyme-linked immunosorbent
      assay (ELISA) for determination of the PAH benzo[a]pyrene (B[a]P) in vegetable
      oils. Different molecularly imprinted polymers (MIPs) were prepared using non
      covalent 4-vinylpyridine/divinylbenzene co-polymerization at different ratios and
      dichloromethane as porogen. Imprinting was done with a template mixture of
      phenanthrene and pyrene yielding a broad-specific polymer for PAHs with a maximum
      binding capacity (Q) of ~32 MUg B[a]P per 50 mg of polymer. The vegetable oil/n
      hexane mixture (1:1, (v/v)) was pre-extracted with acetonitrile, the solvent
      evaporated, the residue reconstituted in n-hexane and subjected to MISPE. The
      successive washing with n-hexane and isopropanol revealed most suitable to remove
      lipid matrix constituents. After elution of bound PAHs from MISPE column with
      dichloromethane, the solvent was evaporated, the residue reconstituted with
      dimethyl sulfoxide and diluted 100-fold with methanol/water (10:90, (v/v)) for
      analysis of B[a]P equivalents with an ELISA. The B[a]P recovery rates in spiked
      vegetable oil samples of different fatty acid composition were determined between
      63% and 114%. The presence of multiple PAHs in the oil sample, because of MIP
      selectivity and cross-reactivity of the ELISA, could yield overestimated B[a]P
      values. 

PMID- 24887046
TI  - Smoking and smoking cessation effects on oncological outcomes in nonmuscle
      invasive bladder cancer.
AB  - PURPOSE OF REVIEW: Cigarette smoking is the best established risk factor for the
      development of bladder cancer. Nevertheless, the impact of smoking and smoking
      cessation on the outcomes of patients with nonmuscle invasive bladder cancer
      (NMIBC) remains poorly investigated. RECENT FINDINGS: Currently, there are no
      prospective studies analyzing the impact of smoking on NMIBC outcomes. The
      majority of retrospective studies found an association between smoking status as
      well as cumulative lifetime exposure and disease recurrence. A recently published
      study demonstrated a significant impact of smoking on disease progression;
      however, the evidence regarding this end point is weak. There are insufficient
      data investigating the impact on cancer-specific and overall survival in patients
      with NMIBC. Assessment of the impact of smoking on particular subsets of patients
      with NMIBC including T1 or high-risk disease, patients receiving intravesical
      therapies, or sex-specific differences is limited because of a lack of data and
      controversial findings. Smoking cessation seems to mitigate the detrimental
      effects on outcomes. SUMMARY: Although there are limited data, the growing body
      of evidence indicates that smoking increases the risk of disease recurrence and
      potentially disease progression in patients with NMIBC. Current and heavy long
      term smokers seem to be at the greatest risk for both end points. Smoking
      cessation may limit these effects thereby improving prognosis. To improve our
      understanding of the associations of this important, modifiable risk factor with
      outcomes in patients with NMIBC, smoking should be incorporated into clinical
      trial design and analysis. It is the duty of each urologist to raise awareness
      regarding the greatest preventable cause of the development of bladder cancer,
      morbidity, and mortality.

PMID- 24887047
TI  - The burden of bladder cancer care: direct and indirect costs.
AB  - PURPOSE OF REVIEW: Bladder cancer is a common, complex, and costly disease. Every
      year in the USA, bladder cancer is responsible for 70 ,000 diagnosed cases and
      over 15, 000 deaths. Once diagnosed, patients with nonmuscle invasive bladder
      cancer (NMIBC) are committed to a lifetime of invasive procedures and potential
      hospitalizations that result in substantial direct and indirect costs. RECENT
      FINDINGS: Bladder cancer is the most costly cancer among the elderly, estimated
      at nearly $4 billion per year, and has the highest cost of any cancer when
      categorized on a per patient basis. The direct economic cost of NMIBC is fueled
      by the need for lifelong cystoscopic examination and variations in treatment
      algorithms. This fiscal burden is further compounded by the indirect impact on
      psychological health and quality of life of patients and their families. Despite
      the development of new technologies, such as novel urinary biomarkers and
      innovative cystoscopic methods, no alternative to cystoscopic surveillance has
      been established. SUMMARY: The management of patients with NMIBC is responsible
      for a substantial financial burden with indirect costs that extend beyond
      quantifiable direct costs.

PMID- 24887048
TI  - Relationship between surgical volume and outcomes in nephron-sparing surgery.
AB  - PURPOSE OF REVIEW: Provider volume has been shown to affect outcomes of various
      surgical procedures. Because of its technical complexity, it is likely that
      partial nephrectomy outcomes can be affected by hospital and/or surgeon volume.
      However, until recently, there were few publications on the subject. Our
      objective is to discuss recent findings on the impact of surgical volume on
      partial nephrectomy outcomes. RECENT FINDINGS: Two studies found a link between
      the number of partial nephrectomy performed at an institution and postoperative
      outcomes. Data extrapolated from articles on learning curve of laparoscopic
      partial nephrectomy suggest that surgeon volume can also affect partial
      nephrectomy outcomes. Partial nephrectomy is underused in low-volume centers.
      Robotic partial nephrectomy has a shorter learning curve compared to laparoscopic
      partial nephrectomy and may increase the use of partial nephrectomy vs. radical
      nephrectomy. Results on the impact of provider volume on the surgical approach
      are conflicting. SUMMARY: There are few publications suggesting an impact of
      hospital volume on partial nephrectomy outcomes but the importance of the surgeon
      volume remains unclear. Higher surgical volume is associated with increased use
      of partial nephrectomy.

PMID- 24887050
TI  - Comparison of the incisions for the open surgical treatment of gluteal muscle
      contracture.
AB  - Gluteal muscle contracture is not very common, but cases are still seen in China.
      Open surgical treatment is considered as an efficient method to treat this
      disease. However, the type of incision that can provide best results is yet to be
      determined. The authors therefore compared various incisions to determine the
      better one. In this retrospective study, patients who underwent surgery with a
      traverse straight incision, a curved incision, a longitudinal straight incision,
      or an 'S'-shaped incision above the greater trochanter were enrolled and divided
      into four groups: A, B, C, and D. In each group, the patients were divided into
      different levels according to a specific standard. The four groups were compared
      in terms of incision length, postoperative drainage amounts, wound healing rates,
      visual analog scale scores, and improvement in the degree of range of motion
      (ROM). During the follow-up period, the validity of the results, complications,
      and recurrent cases were evaluated. In our study, incision length and visual
      analog scale score of the four groups showed no significant differences (P>0.05).
      Wound healing rates, drainage amount, improvement in ROM, validity of the
      results, and recurrences in group D were significantly the best (P<0.05). No
      significant differences in wound healing rates, drainage amount, and improvement
      in ROM were found in groups A, B, and C. In terms of validity of the results and
      1-year recurrence, no significant difference was observed between groups A and B;
      however, these factors were better than those in group C. We concluded that the
      'S'-shaped incision above the greater trochanter is the most efficient among the
      incisions described in this study. This incision has the following advantages:
      clear exposure, less damage, high safety rate, excellent results, and low
      recurrence rate. 

PMID- 24887051
TI  - Sleeve fracture of the patella with lateral slip of the retinaculum: a case
      report in an 11-year-old child.
AB  - Adolescents are susceptible to patellar sleeve fractures. We present an
      interesting case of a patellar sleeve fracture in an 11-year-old child with
      lateral slip of the retinacular sleeve. Clinical assessment was difficult;
      however, an MRI scan confirmed the diagnosis. Surgical repair was undertaken, and
      the retinacular sleeve was repaired along with repair of the patellar tendon. The
      patient recovered well after surgery and underwent physiotherapy. A patellar
      sleeve fracture should always be suspected in patients less than 16 years of age,
      particularly in those with indirect acute trauma to the knee. Prompt surgical
      repair is important to achieve full functional recovery. 

PMID- 24887052
TI  - Paresis of the L5 nerve root after reduction of low-grade lumbosacral dysplastic
      spondylolisthesis: a case report.
AB  - We present a unique case of a 16-year-old patient who underwent lumbar
      decompression surgery (L4-S1), low-grade spondylolisthesis reduction surgery at
      L5-S1, and posterior instrumented fusion from L4 to the pelvis. Neurologic
      monitoring did not show any sustained changes throughout the operation. The
      patient was awoken from endotracheal anesthesia with grade 0 muscle function of
      the left extensor hallucis longus and tibialis anterior muscles resulting in left
      sided foot drop. At the last follow-up 12 months after surgery, the patient had
      partial recovery, with grade 4 muscle function of the left extensor hallucis
      longus and tibialis anterior muscles. We suggest that early identification with
      direct nerve root stimulation and wake-up test immediately after reduction of
      spondylolisthesis will allow prompt release of the reduction and further foramen
      exploration, and increase the possibility of good postoperative nerve root
      recovery. 

PMID- 24887049
TI  - Systemic glucose variability predicts cerebral metabolic distress and mortality
      after subarachnoid hemorrhage: a retrospective observational study.
AB  - INTRODUCTION: Cerebral glucose metabolism and energy production are affected by
      serum glucose levels. Systemic glucose variability has been shown to be
      associated with poor outcome in critically ill patients. The objective of this
      study was to assess whether glucose variability is associated with cerebral
      metabolic distress and outcome after subarachnoid hemorrhage. METHODS: A total of
      28 consecutive comatose patients with subarachnoid hemorrhage, who underwent
      cerebral microdialysis and intracranial pressure monitoring, were studied.
      Metabolic distress was defined as lactate/pyruvate ratio (LPR) >40. The
      relationship between daily glucose variability, the development of cerebral
      metabolic distress and hospital outcome was analyzed using a multivariable
      general linear model with a logistic link function for dichotomized outcomes.
      RESULTS: Daily serum glucose variability was expressed as the standard deviation
      (SD) of all serum glucose measurements. General linear models were used to relate
      this predictor variable to cerebral metabolic distress and mortality at hospital
      discharge. A total of 3,139 neuromonitoring hours and 181 days were analyzed.
      After adjustment for Glasgow Coma Scale (GCS) scores and brain glucose, SD was
      independently associated with higher risk of cerebral metabolic distress
      (adjusted odds ratio = 1.5 (1.1 to 2.1), P = 0.02). Increased variability was
      also independently associated with in hospital mortality after adjusting for age,
      Hunt Hess, daily GCS and symptomatic vasospasm (P = 0.03). CONCLUSIONS: Increased
      systemic glucose variability is associated with cerebral metabolic distress and
      increased hospital mortality. Therapeutic approaches that reduce glucose
      variability may impact on brain metabolism and outcome after subarachnoid
      hemorrhage.

PMID- 24887053
TI  - Slipped capital femoral epiphysis in identical twins: does human leucocyte
      antigen matter?
AB  - Slipped capital femoral epiphysis (SCFE) is a well-known disorder of the hip in
      adolescents that is characterized by displacement of the capital femoral
      epiphysis from the metaphysis through the physis. Multiple theories have been
      proposed for the aetiology of idiopathic SCFE, and it is likely a result of both
      biomechanical and biochemical factors. The association between human leucocyte
      antigen (HLA) and certain rheumatic diseases is well established. One of the
      strongest associations is between the HLA class I antigen B27 and ankylosing
      spondylitis. Several DRB 1 alleles are associated with susceptibility to and
      severity of rheumatoid arthritis. The quest to find similar markers have fuelled
      the suggestion that SCFE may be linked to the presence of a specific HLA antigen.
      We present a case report of an identical twin presenting with SCFE. An 11-year
      old girl presented with pain in her hip for last few days and difficulty in
      mobilizing. Radiographs showed SCFE that was fixed in situ with one screw.
      Eighteen months later her twin sister presented with pain in hip and limp of 3
      week duration with no preceding history of trauma. Radiographs showed SCFE that
      was fixed in situ with one screw. Both sisters have made full recovery with no
      pain or residual limp. HLA typing of the twins showed variations between diseases
      and HLA phenotype in different population groups with SCFE. This is the fifth
      case of identical twins presenting with SCFE with HLA class I analysis and only
      the second case report with both HLA class I and class II analysis. Our case
      report further emphasizes findings from previous studies that there is no
      relationship between SCFE and a specific HLA class I or class II antigen. LEVEL
      OF EVIDENCE: Level V.

PMID- 24887055
TI  - Early and widespread injury of astrocytes in the absence of demyelination in
      acute haemorrhagic leukoencephalitis.
AB  - Acute hemorrhagic leukoencephalitis (AHL) is a fulminant demyelinating disease of
      unknown etiology. Most cases are fatal within one week from onset. AHL pathology
      varies with the acuteness of disease. Hemorrhages, vessel fibrinoid necrosis,
      perivascular fibrin exudation, edema and neutrophilic inflammation are early
      features, while perivascular demyelination, microglial foci and myelin-laden
      macrophages appear later. Reactive astrocytosis is not present in early
      hemorrhagic non-demyelinated lesions, but is seen in older lesions. This case
      report presents the pathology of an AHL case with fulminant course and fatal
      outcome within 48 hours from presentation. Severe hemorrhages, edema and
      neutrophilic inflammation in the absence of circumscribed perivascular
      demyelination affected the temporal neocortex and white matter, hippocampus,
      cerebellar cortex and white matter, optic chiasm, mammillary bodies, brainstem,
      cranial nerve roots and leptomeninges. Perivascular end-feet and parenchymal
      processes of astrocytes exhibited impressive swelling in haemorrhagic but non
      demyelinated white matter regions. Astrocytes were dystrophic and displayed
      degenerating processes. Astrocytic swellings and remnants were immunoreactive for
      aquaporin-4, aquaporin-1 and glial fibrillary acidic protein. These morphological
      changes of astrocytes consistent with injury were also observed in haemorrhagic
      and normal appearing cortex. Our findings reinforce that perivascular
      demyelination is not present early in AHL. This is the first study that
      highlights the early and widespread astrocytic injury in the absence of
      demyelination in AHL, suggesting that, similarly to neuromyelitis optica and
      central pontine myelinolysis, demyelination in AHL is secondary to astrocyte
      injury.

PMID- 24887056
TI  - Studying the nutritional beliefs and food practices of Malagasy school children
      parents. A contribution to the understanding of malnutrition in Madagascar.
AB  - Madagascar is severely affected by the problem of children malnutrition. The
      present study aimed at exploring school children Malagasy parents' food practices
      and beliefs structures about the nutritional value of foods, to better understand
      the causes of this malnutrition. A combination of Focus Groups (72 participants),
      and questionnaires (1000 interviewees) was used to evaluate the food beliefs and
      the nutritional habits of low income parents of school age children in urban and
      rural areas of Antananarivo and Antsiranana. The respondents' beliefs were shown
      to focus not only on the nutrient and energetic composition of food, but also to
      involve more general relations between food and health and particularly the
      sanitary properties of food. Compared with such sanitary properties, nutrient
      content was not considered to be the priority in food choice and food
      preparation. The food category considered to be the most nutritive was cereals,
      ahead of protein foods, or vegetables and fruit. Nutritional beliefs were not the
      same in the Antananarivo and Antsiranana areas, nor between urban and rural areas
      of Antsiranana. Different socio-economic contexts, food availability and
      information may explain these differences. This study could guide actors involved
      in nutrition promotion to adapt to specific areas their nutrition programmes in
      the fight against malnutrition. 

PMID- 24887054
TI  - A Gondwanan imprint on global diversity and domestication of wine and cider yeast
      Saccharomyces uvarum.
AB  - In addition to Saccharomyces cerevisiae, the cryotolerant yeast species S. uvarum
      is also used for wine and cider fermentation but nothing is known about its
      natural history. Here we use a population genomics approach to investigate its
      global phylogeography and domestication fingerprints using a collection of
      isolates obtained from fermented beverages and from natural environments on five
      continents. South American isolates contain more genetic diversity than that
      found in the Northern Hemisphere. Moreover, coalescence analyses suggest that a
      Patagonian sub-population gave rise to the Holarctic population through a recent
      bottleneck. Holarctic strains display multiple introgressions from other
      Saccharomyces species, those from S. eubayanus being prevalent in European
      strains associated with human-driven fermentations. These introgressions are
      absent in the large majority of wild strains and gene ontology analyses indicate
      that several gene categories relevant for wine fermentation are overrepresented.
      Such findings constitute a first indication of domestication in S. uvarum. 

PMID- 24887057
TI  - Expression of heparanase in soft tissue sarcomas of adults.
AB  - BACKGROUND: Heparanase is an endo-beta-D-glucuronidase that cleaves heparan
      sulfate chains of proteoglycans, resulting in the disassembly of the
      extracellular matrix. Heparanase has a central role in the development of various
      tumors, and its expression has been associated with increased tumor growth,
      angiogenesis and metastasis, but there is insufficient information about the
      function of heparanase in sarcomas. STUDY AIMS: 1) To evaluate heparanase levels
      in adult soft tissue sarcomas (STS); 2) To examine the correlation between
      heparanase levels and pathological and clinical parameters and treatment outcome.
      METHODS: Pathological specimens of primary or metastatic STS were subjected to
      immunohistochemical analysis applying an anti-heparanase antibody. The clinical
      and the pathological data, together with the data of heparanase levels, were
      evaluated in a logistic regression model for tumor recurrence and survival.
      RESULTS: One hundred and one samples were examined, 55 from primary tumors and 46
      from metastatic sites. A high expression of heparanase was observed in 29 (52.7%)
      and 22 specimens (47.8%), respectively. There was no statistically significant
      difference between heparanase expressions in the primary vs. metastatic sites of
      tumors. Moreover, no correlation was observed between heparanase staining and
      tumor aggressiveness, tumor recurrence or patient survival in various groups of
      patients. CONCLUSION: Expression of heparanase was observed in 50% of the STS, in
      various histological subtypes. A larger study with homogenous groups of specific
      sub-types of STS or stages of disease is required to validate over-expression of
      heparanase as a marker of disease aggressiveness.

PMID- 24887059
TI  - Factors associated with poor outcomes in adults with newly diagnosed ulcerative
      colitis.
AB  - It is a challenge to accurately identify patients with early stage ulcerative
      colitis (UC) who are at highest risk for a poor outcome and therefore might
      require salvage therapy. Several epidemiologic and clinical studies have analyzed
      factors associated with poor prognosis and increased risk for colectomy. We
      review prognostic factors for adults with newly diagnosed UC and discuss which
      patients might benefit from rapid and progressive therapy. Patients with poor
      prognoses tend to be young nonsmokers with high levels of inflammatory
      biomarkers, low levels of hemoglobin, and extensive disease, based on
      colonoscopy. We examine these risk factors in 2 hypothetical patients who have
      been newly diagnosed with UC. 

PMID- 24887058
TI  - Screening for Barrett's esophagus and esophageal adenocarcinoma: rationale,
      recent progress, challenges, and future directions.
AB  - As the incidence and mortality of esophageal adenocarcinoma continue to increase,
      strategies to counter this need to be explored. Screening for Barrett's
      esophagus, which is the known precursor of a large majority of adenocarcinomas,
      has been debated without a firm consensus. Given evidence for and against
      perceived benefits of screening, the multitude of challenges in the
      implementation of such a strategy and in the downstream management of subjects
      with Barrett's esophagus who could be diagnosed by screening, support for
      screening has been modest. Recent advances in the form of development and initial
      accuracy of noninvasive tools for screening, risk assessment tools, and biomarker
      panels to risk stratify subjects with BE, have spurred renewed interest in the
      early detection of Barrett's esophagus and related neoplasia, particularly with
      the advent of effective endoscopic therapy. In this review, we explore in depth
      the potential rationale for screening for Barrett's esophagus, recent advances
      that have the potential of making screening feasible, and also highlight some of
      the challenges that will have to be overcome to develop an effective approach to
      improve the outcomes of subjects with esophageal adenocarcinoma. 

PMID- 24887061
TI  - Synthesis and cytotoxic evaluation of some new[1,3]dioxolo[4,5-g]chromen-8-one
      derivatives.
AB  - BACKGROUND: Homoisoflavonoids are naturally occurring compounds belong to
      flavonoid classes possessing various biological properties such as cytotoxicity.
      In this work, an efficient strategy for the synthesis of novel homoisoflavonoids,
      [1,3]dioxolo[4,5-g]chromen-8-ones, was developed and all compounds were evaluated
      for their cytotoxic activities on three breast cancer cell lines. METHODS: Our
      synthetic route started from benzo[d][1,3]dioxol-5-ol which was reacted with 3
      bromopropanoic acid followed by the reaction of oxalyl chloride to afford 6,7
      dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one. The aldol condensation of the later
      compound with aromatic aldehydes led to the formation of the title compounds.
      Five novel derivatives 4a-e were tested for their cytotoxic activity against
      three human breast cancer cell lines including MCF-7, T47D, and MDA-MB-231 using
      the MTT assay. RESULTS: Among the synthesized compounds, 7-benzylidene-6,7
      dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) exhibited the highest activity
      against three cell lines. Also the analysis of acridine orange/ethidium bromide
      staining results revealed that 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5
      g]chromen-8-one (4a) and 7-(2-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5
      g]chromen-8-one (4b) induced apoptosis in T47D cell line. CONCLUSION: Finally,
      the effect of methoxy group on the cytotoxicity of compounds 4b-4d was
      investigated in and it was revealed that it did not improve the activity of
      [1,3]dioxolo[4,5-g]chromen-8-ones against MCF-7, T47D, and MDA-MB-231.

PMID- 24887060
TI  - Human cytomegalovirus replication is strictly inhibited by siRNAs targeting UL54,
      UL97 or UL122/123 gene transcripts.
AB  - Human cytomegalovirus (HCMV) causes severe sequelae in immunocompromised hosts.
      Current antiviral therapies have serious adverse effects, with treatment in many
      clinical settings problematic, making new therapeutic approaches necessary. We
      examined the in vitro efficacy of small interfering RNAs (siRNAs) targeting the
      HCMV gene transcripts UL54 (DNA polymerase), UL97 (protein kinase) and UL122/123
      (immediate-early proteins) as inhibitors of viral protein expression and virus
      replication in cell cultures. Two siRNAs for each HCMV target (designated A and
      B) were assessed for inhibition efficacy using western blot and standard plaque
      assays. Continuous human embryonic kidney 293T cells were treated with HCMV or
      non-specific scrambled (siSc) siRNA followed by transfection with plasmids
      expressing the target transcripts. Human MRC-5 fibroblasts were HCMV-siRNA or
      siSc treated, infected with HCMV strain AD169 (1 pfu/cell) and HCMV immediate
      early (IE1p72 and IE2p86), early (pp65), early-late (pUL97) and true late (MCP)
      protein and virus progeny production measured during a single round of
      replication. Concordant results showed siUL54B, siUL97A and siUL122B displayed
      the most potent inhibitory effects with a reduction of 92.7%, 99.6% and 93.7% in
      plasmid protein expression, 65.9%, 58.1% and 64.8% in total HCMV protein
      expression and 97.2%, 96.2% and 94.3% (p<0.0001) in viral progeny production
      respectively. Analysing the siRNA inhibitory effects during multiple rounds of
      HCMV replication at a multiplicity of infection of 0.001 pfu/cell, siUL54B,
      siUL97A and siUL122B treatment resulted in a reduction of 80.0%, 59.6% and 84.5%
      in total HCMV protein expression, 52.9%, 49.2% and 58.3% in number of cells
      infected and 98.5%, 91.4% and 99.1% (p<0.0001) in viral progeny production at 7
      dpi respectively. These results suggest potential in vivo siRNA therapies
      targeting the HCMV gene transcripts UL54, UL97 and UL122/123 would be highly
      effective, however, the antiviral efficacy of siRNAs targeting UL97 may be more
      highly dependent on viral load and methods of administration. 

PMID- 24887062
TI  - Intrauterine growth pattern and birthweight discordance in twin pregnancies: a
      retrospective study.
AB  - BACKGROUND: Twins, compared to singletons, have an increased risk of perinatal
      mortality and morbidity, due mainly to a higher prevalence of preterm birth and
      low birthweight. Intrauterine growth restriction (IUGR) is also common and can
      affect one or both fetuses. In some cases, however, one twin is much smaller than
      the other (growth discordance). Usually, high birthweight discordance is
      associated with increased perinatal morbidity. The aim of this study is to
      describe the epidemiological features of a population of twins at birth, with
      particular reference to the interpretation and clinical effects of birthweight
      discordance. METHODS: We evaluated retrospectively the clinical features of 70
      infants born from twin pregnancies and assessed birthweight discordance in 31
      pregnancies where both twins were followed at our institution. Discordance was
      treated both as a continuous and a categorical variable, using a cutoff of 18%.
      Possible relationships between birthweight discordance and other variables, such
      as maternal age, gestational age, birthweight percentile, number of SGA newborns
      in the pair, Hematocrit (Ht) discordance and neonatal anemia, prevalence of
      malformations, neonatal morbidity and death, were analyzed. RESULTS: In our
      cohort birthweight percentile decreased slightly with increasing gestational age.
      Birthweight discordance, on the contrary, increased slightly with the increase of
      gestational age.A high discordance is associated to the presence of one SGA twin,
      with the other AGA or LGA. In our population, all 6 pregnancies in which
      discordance exceeded 18% belonged to this category (one SGA twin).Ht discordance
      at birth is associated to the presence of neonatal anemia in a twin, but it is
      not significantly related to weight discordance.Finally, in our case history,
      weight discordance is not associated in any way with the prevalence of
      malformations, morbidity and mortality. CONCLUSIONS: Birthweight discordance is
      an important indicator of complications that act asymmetrically on the two
      fetuses, affecting intrauterine growth in one of them, and usually determining
      the birth of a SGA infant.Our case history shows a significant statistical
      association between pair discordance and IUGR in one of the twins, but we could
      not demonstrate any relationship between discordance and the prevalence of
      malformations, morbidity and mortality.

PMID- 24887063
TI  - Polyol-mediated C-dot formation showing efficient Tb3+/Eu3+ emission.
AB  - C-dots (3-5 nm in diameter) obtained by most simple heating of polyols (glycerol,
      diethylene glycol and PEG 400) show intense blue and green emission (50% quantum
      yield). Upon modification with TbCl3/EuCl3, energy transfer from the C-dots to
      the rare-earth metal results in line-type Tb(3+) (green)/Eu(3+) (red) emission
      with quantum yields up to 85%. 

PMID- 24887065
TI  - Exogenous sphingosine-1-phosphate boosts acclimatization in rats exposed to acute
      hypobaric hypoxia: assessment of haematological and metabolic effects.
AB  - BACKGROUND: The physiological challenges posed by hypobaric hypoxia warrant
      exploration of pharmacological entities to improve acclimatization to hypoxia.
      The present study investigates the preclinical efficacy of sphingosine-1
      phosphate (S1P) to improve acclimatization to simulated hypobaric hypoxia.
      EXPERIMENTAL APPROACH: Efficacy of intravenously administered S1P in improving
      haematological and metabolic acclimatization was evaluated in rats exposed to
      simulated acute hypobaric hypoxia (7620 m for 6 hours) following S1P pre
      treatment for three days. MAJOR FINDINGS: Altitude exposure of the control rats
      caused systemic hypoxia, hypocapnia (plausible sign of hyperventilation) and
      respiratory alkalosis due to suboptimal renal compensation indicated by an overt
      alkaline pH of the mixed venous blood. This was associated with pronounced energy
      deficit in the hepatic tissue along with systemic oxidative stress and
      inflammation. S1P pre-treatment improved blood oxygen-carrying-capacity by
      increasing haemoglobin, haematocrit, and RBC count, probably as an outcome of
      hypoxia inducible factor-1alpha mediated erythropoiesis and renal S1P receptor 1
      mediated haemoconcentation. The improved partial pressure of oxygen in the blood
      could further restore aerobic respiration and increase ATP content in the hepatic
      tissue of S1P treated animals. S1P could also protect the animals from hypoxia
      mediated oxidative stress and inflammation. CONCLUSION: The study findings
      highlight S1P's merits as a preconditioning agent for improving acclimatization
      to acute hypobaric hypoxia exposure. The results may have long term clinical
      application for improving physiological acclimatization of subjects venturing
      into high altitude for occupational or recreational purposes.

PMID- 24887068
TI  - Feasibility of proton transmission-beam stereotactic ablative radiotherapy versus
      photon stereotactic ablative radiotherapy for lung tumors: a dosimetric and
      feasibility study.
AB  - Stereotactic ablative radiotherapy is being increasingly adopted in the treatment
      of lung tumors. The use of proton beam therapy can further reduce dose to normal
      structures. However, uncertainty exists in proton-based treatment plans,
      including range uncertainties, large sensitivity to position uncertainty, and
      calculation of dose deposition in heterogeneous areas. This study investigated
      the feasibility of proton transmission beams, i.e. without the Bragg peak, to
      treat lung tumors with stereotactic ablative radiotherapy. We compared three
      representative treatment plans using proton transmission beams versus conformal
      static-gantry photon beams. It was found that proton treatment plans using
      transmission beams passing through the patient were feasible and demonstrated
      lower dose to normal structures and markedly reduced treatment times than photon
      plans. This is the first study to demonstrate the feasibility of proton-based
      stereotactic ablative radiotherapy planning for lung tumors using proton
      transmission beams alone. Further research using this novel approach for proton
      based planning is warranted. 

PMID- 24887064
TI  - Seminoma and embryonal carcinoma footprints identified by analysis of integrated
      genome-wide epigenetic and expression profiles of germ cell cancer cell lines.
AB  - BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a
      precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the
      most common cancer in young men, subdivided in seminoma (SE) and non-seminoma
      (NS). During physiological germ cell formation/maturation, epigenetic processes
      guard homeostasis by regulating the accessibility of the DNA to facilitate
      transcription. Epigenetic deregulation through genetic and environmental
      parameters (i.e. genvironment) could disrupt embryonic germ cell development,
      resulting in delayed or blocked maturation. This potentially facilitates the
      formation of CIS and progression to invasive GCC. Therefore, determining the
      epigenetic and functional genomic landscape in GCC cell lines could provide
      insight into the pathophysiology and etiology of GCC and provide guidance for
      targeted functional experiments. RESULTS: This study aims at identifying
      epigenetic footprints in SE and EC cell lines in genome-wide profiles by studying
      the interaction between gene expression, DNA CpG methylation and histone
      modifications, and their function in the pathophysiology and etiology of GCC. Two
      well characterized GCC-derived cell lines were compared, one representative for
      SE (TCam-2) and the other for EC (NCCIT). Data were acquired using the Illumina
      HumanHT-12-v4 (gene expression) and HumanMethylation450 BeadChip (methylation)
      microarrays as well as ChIP-sequencing (activating histone modifications
      (H3K4me3, H3K27ac)). Results indicate known germ cell markers not only to be
      differentiating between SE and NS at the expression level, but also in the
      epigenetic landscape. CONCLUSION: The overall similarity between TCam-2/NCCIT
      support an erased embryonic germ cell arrested in early gonadal development as
      common cell of origin although the exact developmental stage from which the tumor
      cells are derived might differ. Indeed, subtle difference in the (integrated)
      epigenetic and expression profiles indicate TCam-2 to exhibit a more germ cell
      like profile, whereas NCCIT shows a more pluripotent phenotype. The results
      provide insight into the functional genome in GCC cell lines.

PMID- 24887067
TI  - Spatial dependencies between large-scale brain networks.
AB  - Functional neuroimaging reveals both increases (task-positive) and decreases
      (task-negative) in neural activation with many tasks. Many studies show a
      temporal relationship between task positive and task negative networks that is
      important for efficient cognitive functioning. Here we provide evidence for a
      spatial relationship between task positive and negative networks. There are
      strong spatial similarities between many reported task negative brain networks,
      termed the default mode network, which is typically assumed to be a spatially
      fixed network. However, this is not the case. The spatial structure of the DMN
      varies depending on what specific task is being performed. We test whether there
      is a fundamental spatial relationship between task positive and negative
      networks. Specifically, we hypothesize that the distance between task positive
      and negative voxels is consistent despite different spatial patterns of
      activation and deactivation evoked by different cognitive tasks. We show
      significantly reduced variability in the distance between within-condition task
      positive and task negative voxels than across-condition distances for four
      different sensory, motor and cognitive tasks--implying that deactivation patterns
      are spatially dependent on activation patterns (and vice versa), and that both
      are modulated by specific task demands. We also show a similar relationship
      between positively and negatively correlated networks from a third 'rest'
      dataset, in the absence of a specific task. We propose that this spatial
      relationship may be the macroscopic analogue of microscopic neuronal organization
      reported in sensory cortical systems, and that this organization may reflect
      homeostatic plasticity necessary for efficient brain function.

PMID- 24887069
TI  - Perioperative corticosteroids for preventing complications following facial
      plastic surgery.
AB  - BACKGROUND: Early recovery is an important factor for people undergoing facial
      plastic surgery. However, the normal inflammatory processes that are a
      consequence of surgery commonly cause oedema (swelling) and ecchymosis
      (bruising), which are undesirable complications. Severe oedema and ecchymosis
      delay full recovery, and may make patients dissatisfied with procedures.
      Perioperative corticosteroids have been used in facial plastic surgery with the
      aim of preventing oedema and ecchymosis. OBJECTIVES: To determine the effects,
      including safety, of perioperative administration of corticosteroids for
      preventing complications following facial plastic surgery in adults. SEARCH
      METHODS: In January 2014, we searched the following electronic databases: the
      Cochrane Wounds Group Specialised Register; the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE
      (In-Process & Other Non-Indexed Citations); Ovid Embase; EBSCO CINAHL; and
      Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS). There were
      no restrictions on the basis of date or language of publication. SELECTION
      CRITERIA: We included RCTs that compared the administration of perioperative
      systemic corticosteroids with another intervention, no intervention or placebo in
      facial plastic surgery. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened the trials for inclusion in the review, appraised trial
      quality and extracted data. MAIN RESULTS: We included 10 trials, with a total of
      422 participants, that addressed two of the outcomes of interest to this review:
      swelling (oedema) and bruising (ecchymosis). Nine studies on rhinoplasty used a
      variety of different types, and doses, of corticosteroids. Overall, the results
      of the included studies showed that there is some evidence that perioperative
      administration of corticosteroids decreases formation of oedema over the first
      two postoperative days. Meta-analysis was only possible for two studies, with a
      total of 60 participants, and showed that a single perioperative dose of 10 mg
      dexamethasone decreased oedema formation in the first two days after surgery (SMD
      = -1.16, 95% CI: -1.71 to -0.61, low quality evidence). The evidence for
      ecchymosis was less consistent across the studies, with some contradictory
      results, but overall there was some evidence that perioperatively administered
      corticosteroids decreased ecchymosis formation over the first two days after
      surgery (SMD = -1.06, 95% CI:-1.47 to -0.65, two studies, 60 participants, low
      quality evidence ). The difference was not maintained after this initial period.
      One study, with 40 participants, showed that high doses of methylprednisolone
      (over 250 mg) decreased both ecchymosis and oedema between the first and seventh
      postoperative days. The only study that assessed facelift surgery identified no
      positive effect on oedema with preoperative administration of corticosteroids.
      Five trials did not report on harmful (adverse) effects; four trials reported
      that there were no adverse effects; and one trial reported adverse effects in two
      participants treated with corticosteroids as well as in four participants treated
      with placebo. None of the studies reported recovery time, patient satisfaction or
      quality of life. The studies included were all at an unclear risk of selection
      bias and at low risk of bias for other domains. AUTHORS' CONCLUSIONS: There is
      limited evidence for rhinoplasty that a single perioperative dose of
      corticosteroids decreases oedema and ecchymosis formation over the first two
      postoperative days, but the difference is not maintained after this period. There
      is also limited evidence that high doses of corticosteroids decrease both
      ecchymosis and oedema between the first and seventh postoperative days. The
      clinical significance of this decrease is unknown and there is little evidence
      available regarding the safety of this intervention. More studies are needed
      because at present the available evidence does not support the use of
      corticosteroids for prevention of complications following facial plastic surgery.

PMID- 24887070
TI  - Hypoxia-induced miR-15a promotes mesenchymal ablation and adaptation to hypoxia
      during lung development in chicken.
AB  - The lungs undergo changes that are adaptive for high elevation in certain animal
      species. In chickens, animals bred at high elevations (e.g., Tibet chickens) are
      better able to hatch and survive under high-altitude conditions. In addition,
      lowland chicken breeds undergo physiological effects and suffer greater mortality
      when they are exposed to hypoxic conditions during embryonic development.
      Although these physiological effects have been noted, the mechanisms that are
      responsible for hypoxia-induced changes in lung development and function are not
      known. Here we have examined the role of a particular microRNA (miRNA) in the
      regulation of lung development under hypoxic conditions. When chicks were
      incubated in low oxygen (hypoxia), miR-15a was significantly increased in
      embryonic lung tissue. The expression level of miR-15a in hypoxic Tibet chicken
      embryos increased and remained relatively high at embryonic day (E)16-20, whereas
      in normal chickens, expression increased and peaked at E19-20, at which time the
      cross-current gas exchange system (CCGS) is developing. Bcl-2 was a
      translationally repressed target of miR-15a in these chickens. miR-16, a cluster
      and family member of miR-15a, was detected but did not participate in the
      posttranscriptional regulation of bcl-2. Around E19, the hypoxia-induced decrease
      in Bcl-2 protein resulted in apoptosis in the mesenchyme around the migrating
      tubes, which led to an expansion and migration of the tubes that would become the
      air capillary network and the CCGS. Thus, interfering with miR-15a expression in
      lung tissue may be a novel therapeutic strategy for hypoxia insults and altitude
      adaptation. 

PMID- 24887071
TI  - Decreased interleukin 27 expression is associated with active uveitis in Behcet's
      disease.
AB  - INSTRUCTION: Interleukin 27 (IL-27) is an important regulator of the
      proinflammatory T-cell response. In this study, we investigated its role in the
      pathogenesis of Behcet's disease (BD). METHODS: IL-27 mRNA in peripheral blood
      mononuclear cells (PBMCs) was examined by performing RT-PCRs. Cytokine levels in
      sera or supernatants of PBMCs, naive CD4(+) T cells, dendritic cells (DCs) and
      DC/T cells were determined by enzyme-linked immunosorbent assay. We used RNA
      interference in naive CD4(+) T cells to study the role of interferon regulatory
      factor 8 (IRF8) in the inhibitory effect of IL-27 on Th17 cell differentiation.
      Flow cytometry was used to evaluate the frequency of IL-17- and interferon gamma
      producing T cells. RESULTS: The expression of IL-27p28 mRNA by PBMCs and IL-27 in
      the sera and supernatants of cultured PBMCs were markedly decreased in patients
      with active BD. A higher frequency of IL-17-producing CD4(+) T (Th17) cells and
      increased IL-17 production under Th17 polarizing conditions were observed in
      patients with active BD. IL-27 significantly inhibited Th17 cell differentiation.
      Downregulation of IRF8 by RNA interference abrogated the suppressive effect of IL
      27 on Th17 differentiation. IL-27 inhibited the production of IL-1beta, IL-6 and
      IL-23, but promoted IL-10 production, by DCs. IL-27-treated DCs inhibited both
      the Th1 and Th17 cell responses. CONCLUSIONS: The results of the present study
      suggest that a decreased IL-27 expression is associated with disease activity in
      BD patients. Low IL-27 expression may result in a higher Th1 and Th17 cell
      response and thereby promote the autoinflammatory reaction observed in BD.
      Manipulation of IL-27 may offer a new treatment modality for this disease.

PMID- 24887072
TI  - Liquid polystyrene: a room-temperature photocurable soft lithography compatible
      pour-and-cure-type polystyrene.
AB  - Materials matter in microfluidics. Since the introduction of soft lithography as
      a prototyping technique and polydimethylsiloxane (PDMS) as material of choice the
      microfluidics community has settled with using this material almost exclusively.
      However, for many applications PDMS is not an ideal material given its limited
      solvent resistance and hydrophobicity which makes it especially disadvantageous
      for certain cell-based assays. For these applications polystyrene (PS) would be a
      better choice. PS has been used in biology research and analytics for decades and
      numerous protocols have been developed and optimized for it. However, PS has not
      found widespread use in microfluidics mainly because, being a thermoplastic
      material, it is typically structured using industrial polymer replication
      techniques. This makes PS unsuitable for prototyping. In this paper, we introduce
      a new structuring method for PS which is compatible with soft lithography
      prototyping. We develop a liquid PS prepolymer which we term as "Liquid
      Polystyrene" (liqPS). liqPS is a viscous free-flowing liquid which can be cured
      by visible light exposure using soft replication templates, e.g., made from PDMS.
      Using liqPS prototyping microfluidic systems in PS is as easy as prototyping
      microfluidic systems in PDMS. We demonstrate that cured liqPS is (chemically and
      physically) identical to commercial PS. Comparative studies on mouse fibroblasts
      L929 showed that liqPS cannot be distinguished from commercial PS in such
      experiments. Researchers can develop and optimize microfluidic structures using
      liqPS and soft lithography. Once the device is to be commercialized it can be
      manufactured using scalable industrial polymer replication techniques in PS--the
      material is the same in both cases. Therefore, liqPS effectively closes the gap
      between "microfluidic prototyping" and "industrial microfluidics" by providing a
      common material.

PMID- 24887074
TI  - Military medical torture and denial, redux.

PMID- 24887073
TI  - The prevalence of confirmed maltreatment among US children, 2004 to 2011.
AB  - IMPORTANCE: Child maltreatment is a risk factor for poor health throughout the
      life course. Existing estimates of the proportion of the US population maltreated
      during childhood are based on retrospective self-reports. Records of officially
      confirmed maltreatment have been used to produce annual rather than cumulative
      counts of maltreated individuals. OBJECTIVE: To estimate the proportion of US
      children with a report of maltreatment (abuse or neglect) that was indicated or
      substantiated by Child Protective Services (referred to as confirmed
      maltreatment) by 18 years of age. DESIGN, SETTING, AND PARTICIPANTS: The National
      Child Abuse and Neglect Data System (NCANDS) Child File includes information on
      all US children with a confirmed report of maltreatment, totaling 5,689,900
      children (2004-2011). We developed synthetic cohort life tables to estimate the
      cumulative prevalence of confirmed childhood maltreatment by 18 years of age.
      MAIN OUTCOMES AND MEASURES: The cumulative prevalence of confirmed child
      maltreatment by race/ethnicity, sex, and year. RESULTS: At 2011 rates, 12.5% (95%
      CI, 12.5%-12.6%) of US children will experience a confirmed case of maltreatment
      by 18 years of age. Girls have a higher cumulative prevalence (13.0% [95% CI,
      12.9%-13.0%]) than boys (12.0% [12.0%-12.1%]). Black (20.9% [95% CI, 20.8%
      21.1%]), Native American (14.5% [14.2%-14.9%]), and Hispanic (13.0% [12.9%
      13.1%]) children have higher prevalences than white (10.7% [10.6%-10.8%]) or
      Asian/Pacific Islander (3.8% [3.7%-3.8%]) children. The risk for maltreatment is
      highest in the first few years of life; 2.1% (95% CI, 2.1%-2.1%) of children have
      confirmed maltreatment by 1 year of age, and 5.8% (5.8%-5.9%), by 5 years of age.
      Estimates from 2011 were consistent with those from 2004 through 2010.
      CONCLUSIONS AND RELEVANCE: Annual rates of confirmed child maltreatment
      dramatically understate the cumulative number of children confirmed to be
      maltreated during childhood. Our findings indicate that maltreatment will be
      confirmed for 1 in 8 US children by 18 years of age, far greater than the 1 in
      100 children whose maltreatment is confirmed annually. For black children, the
      cumulative prevalence is 1 in 5; for Native American children, 1 in 7.

PMID- 24887075
TI  - Complement activation in multiple sclerosis plaques: an immunohistochemical
      analysis.
AB  - INTRODUCTION: Inflammation and complement activation are firmly implicated in the
      pathology of multiple sclerosis; however, the extent and nature of their
      involvement in specific pathological processes such as axonal damage, myelin loss
      and disease progression remains uncertain. This study aims to bring clarity to
      these questions. RESULTS: We describe a detailed immunohistochemical study to
      localise a strategically selected set of complement proteins, activation products
      and regulators in brain and spinal cord tissue of 17 patients with progressive
      multiple sclerosis and 16 control donors, including 9 with central nervous system
      disease. Active, chronic active and chronic inactive multiple sclerosis plaques
      (35 in total) and non-plaque areas were examined.Multiple sclerosis plaques were
      consistently positive for complement proteins (C3, factor B, C1q), activation
      products (C3b, iC3b, C4d, terminal complement complex) and regulators (factor H,
      C1-inhibitor, clusterin), suggesting continuing local complement synthesis,
      activation and regulation despite the absence of other evidence of ongoing
      inflammation. Complement staining was most apparent in plaque and peri-plaque but
      also present in normal appearing white matter and cortical areas to a greater
      extent than in control tissue. C1q staining was present in all plaques suggesting
      a dominant role for the classical pathway. Cellular staining for complement
      components was largely restricted to reactive astrocytes, often adjacent to
      clusters of microglia in close apposition to complement opsonised myelin and
      damaged axons. CONCLUSIONS: The findings demonstrate the ubiquity of complement
      involvement in multiple sclerosis, suggest a pathogenic role for complement
      contributing to cell, axon and myelin damage and make the case for targeting
      complement for multiple sclerosis monitoring and therapy.

PMID- 24887076
TI  - Rationale and protocol for a systematic review and meta-analysis on reduced data
      gathering in people with delusions.
AB  - BACKGROUND: The tendency to form conclusions based on limited evidence is known
      as the 'jumping to conclusions' (JTC) bias, and has been a much studied phenomena
      in individuals with psychosis. Previous reviews have supported the hypothesis
      that a JTC bias is particularly linked to the formation and maintenance of
      delusions. A new systematic review is required as a number of studies have since
      been published, and older reviews are limited by not systematically assessing
      methodological quality or the role of study design in influencing effect size
      estimates. This review aimed to investigate if there is an association between
      psychosis or delusions and JTC bias. METHODS: The current protocol outlines the
      background and methodology for this systematic review and meta-analysis. Eligible
      articles will be identified through searches of the electronic databases
      PsycInfo, PubMed and Medline using relevant search terms, supplemented by hand
      searches of references within eligible articles and key review articles within
      the field. Eligibility criteria were as follows: studies must recruit individuals
      with: i) schizophrenia spectrum conditions or ii) experiences of delusions. Case
      control, cross-sectional, observational and prospective designs will be included
      but treatment trials and experimental studies excluded. Studies must use the
      beads task to assess JTC or a conceptually equivalent task. The outcomes will be
      the average number of 'draws to a decision' in the beads task (or related
      variant) and the proportion of the sample judged to demonstrate a JTC bias.
      Literature searches, study selection, data extraction, risk of bias assessment
      and outcome quality assessment will be undertaken by two independent reviewers.
      Meta-analyses will be undertaken for continuous (mean number of 'draws to a
      decision') and binary outcomes (number of people classified as having JTC bias).
      DISCUSSION: Understanding of the size of the JTC effect and the contexts within
      which it occurs is important both in terms of informing models of delusional
      thinking and in guiding treatments for those with delusions or psychosis.
      However, a definitive, up-to-date review and meta-analysis of the JTC bias is
      currently lacking. The proposed review will fill this gap and resolve key issues
      regarding the factors which moderate the JTC bias. PROSPERO REGISTRATION:
      CRD42014007603
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007603.

PMID- 24887078
TI  - Reliability of radiologic measures of hip displacement in a cohort of preschool
      aged children with cerebral palsy.
AB  - BACKGROUND: Radiologic hip surveillance is recommended for children with cerebral
      palsy (CP) at risk of hip displacement. Young children with abnormal proximal
      femoral geometry (Hilgenreiner epiphyseal angle, HEA) may be more likely to
      develop hip displacement, less likely to respond to nonsurgical intervention, and
      may benefit from earlier surgical referral. The reliability of radiographic
      measures of migration percentage (MP) in the immature pelvis of young children
      has been reported in smaller retrospective studies; HEA has not been examined in
      this population. This prospective study describes the reliability of MP and HEA
      in very young children with CP. METHODS: Participants were entered from tertiary
      referral center CP clinics into a prospectively recruited population-based cohort
      for hip surveillance with pelvic radiography using standardized patient position,
      at 18, 24, 30, 36, and 48 months. All Gross Motor Function Classification System
      (GMFCS) levels were included. Two independent raters assessed radiographs for HEA
      and MP. The intraclass correlation coefficient (ICC) was computed as a measure of
      interrater and intrarater reliability. The correlation coefficient between HEA
      and femoral position was computed. RESULTS: Ninety-eight children less than 25
      months (spasticity=83, 85%; GMFCS IV-V=38, 39%), and 114 children 25 to 48 months
      (spasticity=96, 85%; GMFCS IV-V=37, 32%) were included from 133 unique
      participants (spasticity=111, 84%; GMFCS IV-V=42, 32%). Of these 79 children were
      studied in both age groups. Overall interrater and intrarater reliability of MP
      was high [ICC=0.93; 95% confidence interval (CI), 0.91-0.95]; SEM was 3.9%
      (single) and 5.5% (sequential). Perfect concordance for classification of marked
      hip displacement (MP>30%) occurred in 217 cases (95.2%); nonweighted kappa=0.80;
      95% CI, 0.68-0.91. For HEA, overall reliability was high (ICC=0.89; 95% CI, 0.85
      0.93); SEM=4.8% (single) and 6.7% (sequential). Correlation between changes in
      HEA and femoral abduction was poor (coefficient=-0.27, P=0.244). CONCLUSIONS: MP
      and HEA can be reliably applied to very young children with CP, with high
      reliability for both measures. Measured HEA values appear to be independent of
      patient position, and may reflect genuine changes in proximal femoral geometry. A
      longitudinal study should be performed to determine the relationship between HEA
      and later hip outcomes. LEVEL OF EVIDENCE: Level I/II--testing and development of
      diagnostic tests.

PMID- 24887077
TI  - Direct squencing from the minimal number of DNA molecules needed to fill a 454
      picotiterplate.
AB  - The large amount of DNA needed to prepare a library in next generation sequencing
      protocols hinders direct sequencing of small DNA samples. This limitation is
      usually overcome by the enrichment of such samples with whole genome
      amplification (WGA), mostly by multiple displacement amplification (MDA) based on
      phi29 polymerase. However, this technique can be biased by the GC content of the
      sample and is prone to the development of chimeras as well as contamination
      during enrichment, which contributes to undesired noise during sequence data
      analysis, and also hampers the proper functional and/or taxonomic assignments. An
      alternative to MDA is direct DNA sequencing (DS), which represents the
      theoretical gold standard in genome sequencing. In this work, we explore the
      possibility of sequencing the genome of Escherichia coli fs 24 from the minimum
      number of DNA molecules required for pyrosequencing, according to the notion of
      one-bead-one-molecule. Using an optimized protocol for DS, we constructed a
      shotgun library containing the minimum number of DNA molecules needed to fill a
      selected region of a picotiterplate. We gathered most of the reference genome
      extension with uniform coverage. We compared the DS method with MDA applied to
      the same amount of starting DNA. As expected, MDA yielded a sparse and biased
      read distribution, with a very high amount of unassigned and unspecific DNA
      amplifications. The optimized DS protocol allows unbiased sequencing to be
      performed from samples with a very small amount of DNA. 

PMID- 24887080
TI  - Serial derotational casting in congenital scoliosis as a time-buying strategy.
AB  - BACKGROUND: Serial casting is an effective treatment modality in early-onset
      idiopathic scoliosis; however, the role of this method in congenital scoliosis is
      not well studied. METHODS: A total of 11 patients with progressive congenital
      scoliosis were treated with serial cast application. Age at initial cast
      application, magnitudes of the congenital, compensatory and sagittal deformities,
      coronal balance, T1 to T12 height, number of casts and time-in cast per patient,
      subsequent surgical interventions, and complications were evaluated. RESULTS:
      Mean age at the first cast application was 40 months, and the average number of
      cast changes was 6.2 per patient. There were no major complications. The average
      precasting curve magnitude was 70.7 degrees (range, 44 to 88 degrees) and was
      significantly reduced to 55.1 degrees (range, 16 to 78 degrees) at the latest
      follow-up (P=0.005). The average precasting compensatory curve was 55.8 degrees
      (range, 38 to 72 degrees) and was significantly reduced to 39.8 degrees (range,
      23 to 62 degrees) at the latest follow-up (P=0.017). Average T1 to 12 height
      increased from 12.8 cm at post-first cast to a 14.6 cm at the latest follow-up
      (P=0.04). Average time in cast was 26.3 months (range, 13 to 49 mo). During the
      treatment period, none of the patients required surgery for curve progression.
      CONCLUSIONS: Serial derotational casting is a safe and effective time-buying
      strategy to delay the surgical interventions in congenital deformities in the
      short-term follow-up. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 24887079
TI  - Evidence into practice: pediatric orthopaedic surgeon use of removable splints
      for common pediatric fractures.
AB  - OBJECTIVES: Removable splints when compared with circumferential casts in
      randomized trials have been shown to be a safe and cost-effective method of
      managing many common minor distal radius and fibular fractures. This study
      estimated the extent to which this evidence is being implemented in clinical
      practice, and determined the perceived barriers to the adoption of this evidence.
      METHODS: A cross-sectional survey of practicing orthopaedic surgeon members of
      the Pediatric Orthopedic Surgeons of North America (POSNA) was conducted, using a
      22-item online questionnaire, and distributed using a modified Dillman technique.
      Survey questions were derived from and validated by literature review, expert
      opinion, and pilot-testing on the targeted sample before implementation. RESULTS:
      Of the 826 eligible participants, 558 (67.6%) responded to the survey. Of these,
      505 (90.5%) had completed a fellowship in pediatric orthopaedics, 335 (60.0%)
      worked in a university-affiliated setting, and 377 (67.6%) had been in practice
      for <20 years. Only 158/543 [29.1%; 95% confidence interval (CI), 25.28, 32.92]
      reported using a removable splint to treat buckle fractures of the distal radius;
      32 (5.9%; 95% CI, 3.9, 7.9) and 8 (1.5%; 95% CI, 0.5, 2.5) would use such splints
      for minimally displaced greenstick and transverse fractures of the distal radius,
      respectively. For distal fibular avulsion fractures, 122 (22.5%; 95% CI, 19.0,
      26.0) would use a removable splint; 57 (10.5%; 95% CI, 7.9, 13.1) and 28 (5.6%;
      95% CI, 3.7, 7.5) would do so for nondisplaced Salter-Harris I and II fractures
      of the distal fibula, respectively. The most commonly reported perceived barriers
      to application of a removable device were concerns about patient compliance,
      potential complications, and possible medicolegal implications. CONCLUSIONS: Only
      a relatively small proportion of practicing POSNA use such splints for minor
      distal radius and distal fibular fractures. These data support the need for
      implementation of knowledge translation strategies (eg, education) targeted at
      all the stakeholders to encourage pediatric orthopaedic surgeons to change
      practice in keeping with the best evidence for these common and stable injuries.
      LEVEL OF EVIDENCE: Level II.

PMID- 24887082
TI  - The impact of parental accompaniment in paediatric trauma: a helicopter emergency
      medical service (HEMS) perspective.
AB  - Major trauma remains a significant cause of mortality and morbidity in young
      people and adolescents throughout the western world. Both the physical and
      psychological consequences of trauma are well documented and it is shown that
      peri-traumatic factors play a large part in the emotional recovery of children
      involved in trauma. Indeed, parental anxiety levels may play one of the biggest
      roles. There are no publically available guidelines on pre-hospital
      accompaniment, and where research has been done on parental presence it often
      focuses primarily on the parents or staff, rather than the child themselves.
      Whilst acknowledging the impact on parents and staff, the importance of the
      emotional wellbeing of the child should be reinforced, to reduce the likelihood
      of developing symptoms in keeping with post-traumatic stress disorder. This non
      systematic literature review, aims to examine the impact of parental
      accompaniment to hospital, following paediatric trauma, and to help pre-hospital
      clinicians decide whether accompaniment would be of benefit to their patient
      population. The lack of published data does not enable a formal recommendation of
      parental accompaniment in the helicopter to be mandated, though it should be the
      preference in land based conveyance. Future research is needed into the emotional
      recovery of children after trauma, as well as the experiences of patient, parent
      and staff during conveyance.

PMID- 24887081
TI  - Expression and molecular evolution of two DREB1 genes in black poplar (Populus
      nigra).
AB  - Environmental stresses such as low temperature, drought, and high salinity
      significantly affect plant growth and yield. As selective forces, these adverse
      factors play essential roles in shaping phenotypic variation in plant
      populations. Black poplar (Populus nigra) is an economically and ecologically
      important forest tree species with widely distributed populations and is thus
      suitable for experiments detecting evolutionary footprints left by stress. Here,
      we performed expression and evolutionary analysis of two duplicated DREB A1
      subgroup (DREB1) genes, PnDREB68 and PnDREB69, encoding transcription factors
      that are involved in stress responses. The two genes showed partially overlapping
      but distinct expression patterns in response to stresses. These genes were
      strongly and rapidly induced by cold stress in leaves, stems, and roots. In leaf
      tissue, dehydration stress induced the expression of PnDREB68 but not PnDREB69.
      PnDREB69 displayed more rapid responses and longer expression durations than
      PnDREB68 under salt and ABA stress, respectively. Based on single nucleotide
      polymorphism (SNP) analysis, we found significant population genetic
      differentiation, with a greater FST value (0.09189) for PnDREB69 than for
      PnDREB68 (0.07743). Nucleotide diversity analysis revealed a two-fold higher piT
      for PnDREB68 than for PnDREB69 (0.00563 vs. 0.00243), reflecting strong purifying
      selection acting on the former. The results suggest that positive selection acted
      on PnDREB69, as evidenced by neutral testing using Tajima's D statistic. The
      distinct selective forces to which each of the genes was subjected may be
      associated with expression divergence. Linkage disequilibrium (LD) was low for
      the sequenced region, with a higher level for PnDREB68 than for PnDREB69.
      Additionally, analysis of the relationship among carbon isotope ratios, SNP
      classes and gene expression, together with motif and domain analysis, suggested
      that 14 polymorphisms within the two genes may be candidates for an association
      study of important traits such as water use efficiency/drought tolerance in black
      poplar. 

PMID- 24887083
TI  - Tongxinluo protects against pressure overload-induced heart failure in mice
      involving VEGF/Akt/eNOS pathway activation.
AB  - BACKGROUND: It has been demonstrated that Tongxinluo (TXL), a traditional Chinese
      medicine compound, improves ischemic heart disease in animal models via vascular
      endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS).
      The present study aimed to investigate whether TXL protects against pressure
      overload-induced heart failure in mice and explore the possible mechanism of
      action. METHODS AND RESULTS: Transverse aortic constriction (TAC) surgery was
      performed in mice to induce heart failure. Cardiac function was evaluated by
      echocardiography. Myocardial pathology was detected using hematoxylin and eosin
      or Masson trichrome staining. We investigated cardiomyocyte ultrastructure using
      transmission electron microscopy. Angiogenesis and oxidative stress levels were
      determined using CD31 and 8-hydroxydeoxyguanosine immunostaining and
      malondialdehyde assay, respectively. Fetal gene expression was measured using
      real-time PCR. Protein expression of VEGF, phosphorylated (p)-VEGF receptor 2
      (VEGFR2), p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p-eNOS, heme oxygenase-1
      (HO-1), and NADPH oxidase 4 (Nox4) were measured with western blotting. Twelve
      week low- and high-dose TXL treatment following TAC improved cardiac systolic and
      diastolic function and ameliorated left ventricular hypertrophy, fibrosis, and
      myocardial ultrastructure derangement. Importantly, TXL increased myocardial
      capillary density significantly and attenuated oxidative stress injury in failing
      hearts. Moreover, TXL upregulated cardiac nitrite content and the protein
      expression of VEGF, p-VEGFR2, p-PI3K, p-Akt, p-eNOS, and HO-1, but decreased Nox4
      expression in mouse heart following TAC. CONCLUSION: Our findings indicate that
      TXL protects against pressure overload-induced heart failure in mice. Activation
      of the VEGF/Akt/eNOS signaling pathway might be involved in TXL improvement of
      the failing heart.

PMID- 24887084
TI  - Characterization of centromeric histone H3 (CENH3) variants in cultivated and
      wild carrots (Daucus sp.).
AB  - In eukaryotes, centromeres are the assembly sites for the kinetochore, a multi
      protein complex to which spindle microtubules are attached at mitosis and
      meiosis, thereby ensuring segregation of chromosomes during cell division. They
      are specified by incorporation of CENH3, a centromere specific histone H3 variant
      which replaces canonical histone H3 in the nucleosomes of functional centromeres.
      To lay a first foundation of a putative alternative haploidization strategy based
      on centromere-mediated genome elimination in cultivated carrots, in the presented
      research we aimed at the identification and cloning of functional CENH3 genes in
      Daucus carota and three distantly related wild species of genus Daucus varying in
      basic chromosome numbers. Based on mining the carrot transcriptome followed by a
      subsequent PCR-based cloning, homologous coding sequences for CENH3s of the four
      Daucus species were identified. The ORFs of the CENH3 variants were very similar,
      and an amino acid sequence length of 146 aa was found in three out of the four
      species. Comparison of Daucus CENH3 amino acid sequences with those of other
      plant CENH3s as well as their phylogenetic arrangement among other dicot CENH3s
      suggest that the identified genes are authentic CENH3 homologs. To verify the
      location of the CENH3 protein in the kinetochore regions of the Daucus
      chromosomes, a polyclonal antibody based on a peptide corresponding to the N
      terminus of DcCENH3 was developed and used for anti-CENH3 immunostaining of
      mitotic root cells. The chromosomal location of CENH3 proteins in the centromere
      regions of the chromosomes could be confirmed. For genetic localization of the
      CENH3 gene in the carrot genome, a previously constructed linkage map for carrot
      was used for mapping a CENH3-specific simple sequence repeat (SSR) marker, and
      the CENH3 locus was mapped on the carrot chromosome 9. 

PMID- 24887086
TI  - Glass-glass transition during aging of a colloidal clay.
AB  - Colloidal suspensions are characterized by a variety of microscopic interactions,
      which generate unconventional phase diagrams encompassing fluid, gel and glassy
      states and offer the possibility to study new phase and/or state transitions.
      Among these, glass-glass transitions are rare to be found, especially at ambient
      conditions. Here, through a combination of dilution experiments, X-ray photon
      correlation spectroscopy, small angle X-ray scattering, rheological measurements
      and Monte Carlo simulations, we provide evidence of a spontaneous glass-glass
      transition in a colloidal clay. Two different glassy states are distinguished
      with evolving waiting time: a first one, dominated by long-range screened
      Coulombic repulsion (Wigner glass) and a second one, stabilized by orientational
      attractions (Disconnected House of Cards glass), occurring after a much longer
      time. These findings may have implications for heterogeneously charged systems
      out-of-equilibrium and for applications where a fine control of the local order
      and/or long term stability of the amorphous materials are required. 

PMID- 24887085
TI  - Toxic shock syndrome toxin-1-mediated toxicity inhibited by neutralizing
      antibodies late in the course of continual in vivo and in vitro exposure.
AB  - Toxic shock syndrome (TSS) results from the host's overwhelming inflammatory
      response and cytokine storm mainly due to superantigens (SAgs). There is no
      effective specific therapy. Application of immunoglobulins has been shown to
      improve the outcome of the disease and to neutralize SAgs both in vivo and in
      vitro. However, in most experiments that have been performed, antiserum was
      either pre-incubated with SAg, or both were applied simultaneously. To mirror
      more closely the clinical situation, we applied a multiple dose (over five days)
      lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1
      (TSST-1) neutralizing antibody was fully protective, even when administered late
      in the course of the challenge. Kinetic studies on the effect of superantigen
      toxins are scarce. We performed in vitro kinetic studies by neutralizing the
      toxin with antibodies at well-defined time points. T-cell activation was
      determined by assessing T-cell proliferation (3H-thymidine incorporation),
      determination of IL-2 release in the cell supernatant (ELISA), and IL-2 gene
      activation (real-time PCR (RT-PCR)). Here we show that T-cell activation occurs
      continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and
      TNFalpha release into the cell supernatant, even if added at later time points.
      Interference with the prolonged stimulation of proinflammatory cytokines is
      likely to be in vivo relevant, as postexposure treatment protected rabbits
      against the multiple dose lethal SAg challenge. Our results shed new light on the
      treatment of TSS by specific antibodies even at late stages of exposure. 

PMID- 24887087
TI  - The effects of exercise on synaptic stripping require androgen receptor
      signaling.
AB  - Following peripheral nerve injury, synapses are withdrawn from axotomized
      motoneurons. Moderate daily treadmill exercise, which promotes axon regeneration
      of cut peripheral nerves, also influences this synaptic stripping. Different
      exercise protocols are required to promote axon regeneration in male and female
      animals, but the sex requirements for an effect of exercise on synaptic stripping
      are unknown. In male and female C57BL/6 mice, the sciatic nerve was transected in
      the mid-thigh. Mice were then exercised five days per week for two weeks,
      beginning on the third post-transection day. Half of the exercised mice were
      trained by walking slowly (10 M/min) on a level treadmill for one hour per day
      (continuous training). Other mice were interval trained; four short (two min)
      sprints at 20 M/min separated by five minute rest periods. A third group was
      untrained. The extent of synaptic contacts made by structures immunoreactive to
      vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 onto
      axotomized motoneurons was studied in confocal images of retrogradely labeled
      cells. Both types of presumed synaptic contacts were reduced markedly in
      unexercised mice following nerve transection, relative to intact mice. No
      significant reduction was found in continuous trained males or interval trained
      females. Reductions in these contacts in interval trained males and continuous
      trained females were identical to that observed in untrained mice. Treatments
      with the anti-androgen, flutamide, blocked the effect of sex-appropriate exercise
      on synaptic contacts in both males and females. Moderate daily exercise has a
      potent effect on synaptic inputs to axotomized motoneurons. Successful effects of
      exercise have different requirements in males and females, but require androgen
      receptor signaling in both sexes. 

PMID- 24887088
TI  - High polyhydroxybutyrate production in Pseudomonas extremaustralis is associated
      with differential expression of horizontally acquired and core genome
      polyhydroxyalkanoate synthase genes.
AB  - Pseudomonas extremaustralis produces mainly polyhydroxybutyrate (PHB), a short
      chain length polyhydroxyalkanoate (sclPHA) infrequently found in Pseudomonas
      species. Previous studies with this strain demonstrated that PHB genes are
      located in a genomic island. In this work, the analysis of the genome of P.
      extremaustralis revealed the presence of another PHB cluster phbFPX, with high
      similarity to genes belonging to Burkholderiales, and also a cluster, phaC1ZC2D,
      coding for medium chain length PHA production (mclPHA). All mclPHA genes showed
      high similarity to genes from Pseudomonas species and interestingly, this cluster
      also showed a natural insertion of seven ORFs not related to mclPHA metabolism.
      Besides PHB, P. extremaustralis is able to produce mclPHA although in minor
      amounts. Complementation analysis demonstrated that both mclPHA synthases, PhaC1
      and PhaC2, were functional. RT-qPCR analysis showed different levels of
      expression for the PHB synthase, phbC, and the mclPHA synthases. The expression
      level of phbC, was significantly higher than the obtained for phaC1 and phaC2, in
      late exponential phase cultures. The analysis of the proteins bound to the PHA
      granules showed the presence of PhbC and PhaC1, whilst PhaC2 could not be
      detected. In addition, two phasin like proteins (PhbP and PhaI) associated with
      the production of scl and mcl PHAs, respectively, were detected. The results of
      this work show the high efficiency of a foreign gene (phbC) in comparison with
      the mclPHA core genome genes (phaC1 and phaC2) indicating that the ability of P.
      extremaustralis to produce high amounts of PHB could be explained by the
      different expression levels of the genes encoding the scl and mcl PHA synthases. 

PMID- 24887089
TI  - Serum cystatin C predicts vancomycin trough levels better than serum creatinine
      in hospitalized patients: a cohort study.
AB  - INTRODUCTION: Serum cystatin C can improve glomerular filtration rate (GFR)
      estimation over creatinine alone, but whether this translates into clinically
      relevant improvements in drug dosing is unclear. METHODS: This prospective cohort
      study enrolled adults receiving scheduled intravenous vancomycin while
      hospitalized at the Mayo Clinic in 2012. Vancomycin dosing was based on weight,
      serum creatinine with the Cockcroft-Gault equation, and clinical judgment.
      Cystatin C was later assayed from the stored serum used for the creatinine-based
      dosing. Vancomycin trough prediction models were developed by using factors
      available at therapy initiation. Residuals from each model were used to predict
      the proportion of patients who would have achieved the target trough with the
      model compared with that observed with usual care. RESULTS: Of 173 patients
      enrolled, only 35 (20%) had a trough vancomycin level within their target range
      (10 to 15 mg/L or 15 to 20 mg/L). Cystatin C-inclusive models better predicted
      vancomycin troughs than models based upon serum creatinine alone, although both
      were an improvement over usual care. The optimal model used estimated GFR by the
      Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin C
      equation (R(2) = 0.580). This model is expected to yield 54% (95% confidence
      interval 45% to 61%) target trough attainment (P <0.001 compared with the 20%
      with usual care). CONCLUSIONS: Vancomycin dosing based on standard care with
      Cockcroft-Gault creatinine clearance yielded poor trough achievement. The
      developed dosing model with estimated GFR from CKD-EPIcreatinine-cystatin C could
      yield a 2.5-fold increase in target trough achievement compared with current
      clinical practice. Although this study is promising, prospective validation of
      this or similar cystatin C-inclusive dosing models is warranted.

PMID- 24887090
TI  - Restoration of E-cadherin expression by selective Cox-2 inhibition and the
      clinical relevance of the epithelial-to-mesenchymal transition in head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: The epithelial-to-mesenchymal transition (EMT) accompanied by the
      downregulation of E-cadherin has been thought to promote metastasis.
      Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through
      its multifaceted function, and recently its inverse relationship with E-cadherin
      was suggested. The aim of the present study was to investigate whether selective
      Cox-2 inhibitors restore the expression of E-cadherin in head and neck squamous
      cell carcinoma (HNSCC) cells, and to examine the possible correlations of the
      expression levels of EMT-related molecules with clinicopathological factors in
      HNSCC. METHODS: We used quantitative real-time PCR to examine the effects of
      three selective Cox-2 inhibitors, i.e., celecoxib, NS-398, and SC-791 on the gene
      expressions of E-cadherin (CDH-1) and its transcriptional repressors (SIP1,
      Snail, Twist) in the human HNSCC cell lines HSC-2 and HSC-4. To evaluate the
      changes in E-cadherin expression on the cell surface, we used a flowcytometer and
      immunofluorescent staining in addition to Western blotting. We evaluated and
      statistically analyzed the clinicopathological factors and mRNA expressions of
      Cox-2, CDH-1 and its repressors in surgical specimens of 40 patients with tongue
      squamous cell carcinoma (TSCC). RESULTS: The selective Cox-2 inhibitors
      upregulated the E-cadherin expression on the cell surface of the HNSCC cells
      through the downregulation of its transcriptional repressors. The extent of this
      effect depended on the baseline expression levels of both E-cadherin and Cox-2 in
      each cell line. A univariate analysis showed that higher Cox-2 mRNA expression (p
      = 0.037), lower CDH-1 mRNA expression (p = 0.020), and advanced T-classification
      (p = 0.036) were significantly correlated with lymph node metastasis in TSCC. A
      multivariate logistic regression revealed that lower CDH-1 mRNA expression was
      the independent risk factor affecting lymph node metastasis (p = 0.041).
      CONCLUSIONS: These findings suggest that the appropriately selective
      administration of certain Cox-2 inhibitors may have an anti-metastatic effect
      through suppression of the EMT by restoring E-cadherin expression. In addition,
      the downregulation of CDH-1 resulting from the EMT may be closely involved in
      lymph node metastasis in TSCC.

PMID- 24887093
TI  - All in its proper time: monitoring the emergence of a memory bias for novel,
      arousing-negative words in individuals with high and low trait anxiety.
AB  - The well-established memory bias for arousing-negative stimuli seems to be
      enhanced in high trait-anxious persons and persons suffering from anxiety
      disorders. We monitored the emergence and development of such a bias during and
      after learning, in high and low trait anxious participants. A word-learning
      paradigm was applied, consisting of spoken pseudowords paired either with
      arousing-negative or neutral pictures. Learning performance during training
      evidenced a short-lived advantage for arousing-negative associated words, which
      was not present at the end of training. Cued recall and valence ratings revealed
      a memory bias for pseudowords that had been paired with arousing-negative
      pictures, immediately after learning and two weeks later. This held even for
      items that were not explicitly remembered. High anxious individuals evidenced a
      stronger memory bias in the cued-recall test, and their ratings were also more
      negative overall compared to low anxious persons. Both effects were evident, even
      when explicit recall was controlled for. Regarding the memory bias in anxiety
      prone persons, explicit memory seems to play a more crucial role than implicit
      memory. The study stresses the need for several time points of bias measurement
      during the course of learning and retrieval, as well as the employment of
      different measures for learning success. 

PMID- 24887094
TI  - Off-label baclofen prescribing practices among French alcohol specialists:
      results of a national online survey.
AB  - OBJECTIVE: To evaluate, among alcohol specialists belonging to the Societe
      Francaise d'Alcoologie (SFA), i.e., the French Alcohol Society, the proportion of
      physicians who prescribed off-label baclofen for alcohol use disorders (AUDs).
      The secondary objective was to depict the features of individual prescribing and
      monitoring practices. METHODS: On-line survey among 484 French alcohol
      specialists. Physicians were asked whether they prescribed baclofen for AUDs. If
      they did not, the reasons for this choice were investigated. If they did, the
      features of the physician's prescribing practice were explored, including the
      number of patients treated, the mean and maximum doses, the monitoring
      precautions and the pharmacovigilance reporting. Participants were also asked
      about their empirical findings on HDB's efficacy and safety. RESULTS: In total,
      302 physicians (response rate of 62.4%) participated in the survey. Data from 296
      participants were analysed, representing 59.4% of all active prescribing
      physicians belonging to the SFA. HDB use was declared by 74.6% of participants
      (mean dose 109.5 +/- 43.6 mg/d; maximum dose 188 +/- 93.3 mg/d). However, 79.2%
      of prescribers had treated less than 30 patients, and 67.8% used HDB as a second
      line medication. Although HDB was perceived as more efficacious than approved
      drugs by 54.3% of prescribers, it was also declared less safe by 62.8%.
      Nonetheless, 79.7% of prescribers had never filed any pharmacovigilance report.
      Non-prescribers (25.6%) were primarily deterred by the current lack of scientific
      data and official regulation. CONCLUSION: A majority of French alcohol
      specialists reported using HDB, although often on a limited number of their
      patients. HDB was considered efficacious but also potentially hazardous. Despite
      this, physicians reported minimal safety data to the health security system.
      While French health authorities are planning to draft a specific regulatory
      measure for framing off-label HDB prescribing practices, the sustained education
      of prescribers on spontaneous pharmacovigilance reporting should be enhanced.

PMID- 24887092
TI  - Trajectories in glycemic control over time are associated with cognitive
      performance in elderly subjects with type 2 diabetes.
AB  - OBJECTIVE: To study the relationships of long-term trajectories of glycemic
      control with cognitive performance in cognitively normal elderly with type 2
      diabetes (T2D). METHODS: Subjects (n = 835) pertain to a diabetes registry (DR)
      established in 1998 with an average of 18 HbA1c measurements per subject,
      permitting identification of distinctive trajectory groups of HbA1c and examining
      their association with cognitive function in five domains: episodic memory,
      semantic categorization, attention/working memory, executive function, and
      overall cognition. Analyses of covariance compared cognitive function among the
      trajectory groups adjusting for sociodemographic, cardiovascular, diabetes
      related covariates and depression. RESULTS: Subjects averaged 72.8 years of age.
      Six trajectories of HbA1c were identified, characterized by HbA1c level at entry
      into the DR (Higher/Lower), and trend over time (Stable/Decreasing/Increasing).
      Both groups with a trajectory of decreasing HbA1c levels had high HbA1c levels at
      entry into the DR (9.2%, 10.7%), and high, though decreasing, HbA1c levels over
      time. They had the worst cognitive performance, particularly in overall cognition
      (p<0.02) and semantic categorization (p<0.01), followed by that of subjects whose
      HbA1c at entry into the DR was relatively high (7.2%, 7.8%) and increased over
      time. Subjects with stable HbA1c over time had the lowest HbA1c levels at entry
      (6.0%, 6.8%) and performed best in cognitive tests. CONCLUSION: Glycemic control
      trajectories, which better reflect chronicity of T2D than a single HbA1c
      measurement, predict cognitive performance. A trajectory of stable HbA1c levels
      over time is associated with better cognitive function.

PMID- 24887095
TI  - Neurovascular coupling in hippocampus is mediated via diffusion by neuronal
      derived nitric oxide.
AB  - The coupling between neuronal activity and cerebral blood flow (CBF) is essential
      for normal brain function. The mechanisms behind this neurovascular coupling
      process remain elusive, mainly because of difficulties in probing dynamically the
      functional and coordinated interaction between neurons and the vasculature in
      vivo. Direct and simultaneous measurements of nitric oxide (NO) dynamics and CBF
      changes in hippocampus in vivo support the notion that during glutamatergic
      activation nNOS-derived NO induces a time-, space-, and amplitude-coupled
      increase in the local CBF, later followed by a transient increase in local O2
      tension. These events are dependent on the activation of the NMDA-glutamate
      receptor and nNOS, without a significant contribution of endothelial-derived NO
      or astrocyte-neuron signaling pathways. Upon diffusion of NO from active neurons,
      the vascular response encompasses the activation of soluble guanylate cyclase.
      Hence, in the hippocampus, neurovascular coupling is mediated by nNOS-derived NO
      via a diffusional connection between active glutamatergic neurons and blood
      vessels. 

PMID- 24887096
TI  - Polo-like kinase 2 activates an antioxidant pathway to promote the survival of
      cells with mitochondrial dysfunction.
AB  - We previously reported that Polo-like kinase 2 (PLK2) is highly expressed in
      cells with defective mitochondrial respiration and is essential for their
      survival. Although PLK2 has been widely studied as a cell cycle regulator, we
      have uncovered an antioxidant function for this kinase that activates the GSK3
      NRF2 signaling pathway. Here, we report that the expression of PLK2 is responsive
      to oxidative stress and that PLK2 mediates antioxidant signaling by
      phosphorylating GSK3, thereby promoting the nuclear translocation of NRF2. We
      further show that the antioxidant activity of PLK2 is essential for preventing
      p53-dependent necrotic cell death. Thus, the regulation of redox homeostasis by
      PLK2 promotes the survival of cells with dysfunctional mitochondria, which may
      have therapeutic implications for cancer and neurodegenerative diseases. 

PMID- 24887097
TI  - Reshaping chromatin after DNA damage: the choreography of histone proteins.
AB  - DNA damage signaling and repair machineries operate in a nuclear environment
      where DNA is wrapped around histone proteins and packaged into chromatin.
      Understanding how chromatin structure is restored together with the DNA sequence
      during DNA damage repair has been a topic of intense research. Indeed, chromatin
      integrity is central to cell functions and identity. However, chromatin shows
      remarkable plasticity in response to DNA damage. This review presents our current
      knowledge of chromatin dynamics in the mammalian cell nucleus in response to DNA
      double strand breaks and UV lesions. I provide an overview of the key players
      involved in regulating histone dynamics in damaged chromatin regions, focusing on
      histone chaperones and their concerted action with histone modifiers, chromatin
      remodelers and repair factors. I also discuss how these dynamics contribute to
      reshaping chromatin and, by altering the chromatin landscape, may affect the
      maintenance of epigenetic information. 

PMID- 24887098
TI  - Pyruvate formate-lyase interacts directly with the formate channel FocA to
      regulate formate translocation.
AB  - The FNT (formate-nitrite transporters) form a superfamily of pentameric membrane
      channels that translocate monovalent anions across biological membranes. FocA
      (formate channel A) translocates formate bidirectionally but the mechanism
      underlying how translocation of formate is controlled and what governs substrate
      specificity remains unclear. Here we demonstrate that the normally soluble
      dimeric enzyme pyruvate formate-lyase (PflB), which is responsible for
      intracellular formate generation in enterobacteria and other microbes, interacts
      specifically with FocA. Association of PflB with the cytoplasmic membrane was
      shown to be FocA dependent and purified, Strep-tagged FocA specifically retrieved
      PflB from Escherichia coli crude extracts. Using a bacterial two-hybrid system,
      it could be shown that the N-terminus of FocA and the central domain of PflB were
      involved in the interaction. This finding was confirmed by chemical cross-linking
      experiments. Using constraints imposed by the amino acid residues identified in
      the cross-linking study, we provide for the first time a model for the FocA-PflB
      complex. The model suggests that the N-terminus of FocA is important for
      interaction with PflB. An in vivo assay developed to monitor changes in formate
      levels in the cytoplasm revealed the importance of the interaction with PflB for
      optimal translocation of formate by FocA. This system represents a paradigm for
      the control of activity of FNT channel proteins.

PMID- 24887099
TI  - The F420-reducing [NiFe]-hydrogenase complex from Methanothermobacter
      marburgensis, the first X-ray structure of a group 3 family member.
AB  - The reversible redox reaction between coenzyme F420 and H2 to F420H2 is catalyzed
      by an F420-reducing [NiFe]-hydrogenase (FrhABG), which is an enzyme of the energy
      metabolism of methanogenic archaea. FrhABG is a group 3 [NiFe]-hydrogenase with a
      dodecameric quaternary structure of 1.25MDa as recently revealed by high
      resolution cryo-electron microscopy. We report on the crystal structure of FrhABG
      from Methanothermobacter marburgensis at 1.7A resolution and compare it with the
      structures of group 1 [NiFe]-hydrogenases, the only group structurally
      characterized yet. FrhA is similar to the large subunit of group 1 [NiFe]
      hydrogenases regarding its core structure and the embedded [NiFe]-center but is
      different because of the truncation of ca 160 residues that results in similar
      but modified H2 and proton transport pathways and in suitable interfaces for
      oligomerization. The small subunit FrhG is composed of an N-terminal domain
      related to group 1 enzymes and a new C-terminal ferredoxin-like domain carrying
      the distal and medial [4Fe-4S] clusters. FrhB adopts a novel fold, binds one [4Fe
      4S] cluster as well as one FAD in a U-shaped conformation and provides the F420
      binding site at the Si-face of the isoalloxazine ring. Similar electrochemical
      potentials of both catalytic reactions and the electron-transferring [4Fe-4S]
      clusters, determined to be E degrees '~-400mV, are in full agreement with the
      equalized forward and backward rates of the FrhABG reaction. The protein might
      contribute to balanced redox potentials by the aspartate coordination of the
      proximal [4Fe-4S] cluster, the new ferredoxin module and a rather negatively
      charged FAD surrounding.

PMID- 24887101
TI  - High dose tigecycline in critically ill patients with severe infections due to
      multidrug-resistant bacteria.
AB  - INTRODUCTION: The high incidence of multidrug-resistant (MDR) bacteria among
      patients admitted to ICUs has determined an increase of tigecycline (TGC) use for
      the treatment of severe infections. Many concerns have been raised about the
      efficacy of this molecule and increased dosages have been proposed. Our purpose
      is to investigate TGC safety and efficacy at higher than standard doses. METHODS:
      We conducted a retrospective study of prospectively collected data in the ICU of
      a teaching hospital in Rome. Data from all patients treated with TGC for a
      microbiologically confirmed infection were analyzed. The safety profile and
      efficacy of high dosing regimen use were investigated. RESULTS: Over the study
      period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every
      12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem
      resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella
      pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were
      no patients requiring TGC discontinuation or dose reduction because of adverse
      events. In the ventilation-associated pneumonia population (VAP) subgroup (63
      patients: 30 received SD and 33 HD), the only independent predictor of clinical
      cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence
      interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial
      treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential
      Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003)
      were independently associated with clinical failure. CONCLUSIONS: TGC was well
      tolerated at a higher than standard dose in a cohort of critically ill patients
      with severe infections. In the VAP subgroup the high-dose regimen was associated
      with better outcomes than conventional administration due to Gram-negative MDR
      bacteria.

PMID- 24887104
TI  - What is biodiversity? Stepping forward from barcoding to understanding biological
      differences.
AB  - This opinion paper gives personal views of the direction that cataloguing
      biodiversity should be going in. Although molecular taxonomy enables rapid and
      high throughput identification of species, it needs to be anchored to traditional
      taxonomy, because without information of actual biological properties of species,
      DNA barcoding just reports differences in selected DNA sequences, which need not
      have anything to do with the biological properties of the organisms, and the
      reasons for the development of the species. Since functional differences are the
      most common reason behind species differences, the future of cataloguing
      biodiversity and biodiversity research is, in my opinion, in trying to integrate
      genomic research to comparative physiology in order to be able to evaluate which
      functional properties have likely been important in generating biodiversity. This
      task is overwhelming, and requires forgetting the traditional disciplines.
      Further, major problems associated with the present-day treatment of genomic data
      are presented from my viewpoint. 

PMID- 24887103
TI  - Relationship between the percentage of body fat and surrogate indices of fatness
      in male and female Polish active and sedentary students.
AB  - BACKGROUND: Limited data have indicated that body mass index (BMI), waist
      circumference (WC), waist to hip ratio (WHR) and waist to height ratio (WHtR) of
      athletes and young adults provide misleading results concerning body fat content.
      This study was aimed at the evaluation of the relationship between different
      surrogate indices of fatness (BMI, WC, WHR, WHtR and body adiposity index (BAI))
      with the percentage of body fat in Polish students with respect to their sex and
      physical activity. METHODS: A total of 272 students volunteered to participate in
      the study. Of these students, 177 physical education students (90 males and 87
      females) were accepted as active (physical activity of 7 to 9 hours/week); and 95
      students of other specializations (49 males and 46 females) were accepted as
      sedentary (physical activity of 1.5 hours/week). Weight, height, waist and hip
      circumferences were measured, and BMI, WHR, WHtR and BAI were calculated. Body
      fat percentage was assessed using four skinfold measurements. RESULTS:
      Classification of fatness according to the BMI and the percentage of body fat
      have indicated that BMI overestimates fatness in lean subjects (active men and
      women, sedentary men), but underestimates body fat in obese subjects (sedentary
      women). In all groups, BMI, WHR, WHtR and BAI were significantly correlated with
      the percentage of body fat (with the exception of WHR and hip circumference in
      active and sedentary women, respectively). However, coefficients of determination
      not exceeding 50% and Lin's concordance correlation coefficients lower than 0.9
      indicated no relationship between measured and calculated body fat. CONCLUSION:
      The findings in the present study support the concept that irrespective of
      physical activity and sex none of the calculated indices of fatness are useful in
      the determination of body fat in young adults. Thus, it seems that easily
      calculated indices may contribute to distorted body image and unhealthy dietary
      habits observed in many young adults in Western countries, but also in female
      athletes.

PMID- 24887105
TI  - Parenting approaches and digital technology use of preschool age children in a
      Chinese community.
AB  - BACKGROUND: Young children are using digital technology (DT) devices anytime and
      anywhere, especially with the invention of smart phones and the replacement of
      desktop computers with digital tablets. Although research has shown that parents
      play an important role in fostering and supporting preschoolers' developing
      maturity and decisions about DT use, and in protecting them from potential risk
      due to excessive DT exposure, there have been limited studies conducted in Hong
      Kong focusing on parent-child DT use. This study had three objectives: 1) to
      explore parental use of DTs with their preschool children; 2) to identify the DT
      content that associated with child behavioral problems; and 3) to investigate the
      relationships between approaches adopted by parents to control children's DT use
      and related preschooler behavioral problems. METHODS: This exploratory
      quantitative study was conducted in Hong Kong with 202 parents or guardians of
      preschool children between the ages of 3 and 6 attending kindergarten. The
      questionnaire was focused on four aspects, including 1) participants'
      demographics; 2) pattern of DT use; 3) parenting approach to manage the child's
      DT use; and 4) child behavioral and health problems related to DT use. Multiple
      regression analysis was adopted as the main data analysis method for identifying
      the DT or parental approach-related predictors of the preschooler behavioral
      problems. RESULTS: In the multiple linear regression model, the 'restrictive
      approach score' was the only predictor among the three parental approaches
      (B:1.66, 95% CI: [0.21, 3.11], p < 0.05). Moreover, the viewing of antisocial
      behavior cartoons by children also significantly increased the tendency of
      children to have behavioral problem (B:3.84, 95% CI: [1.66, 6.02], p < 0.01).
      CONCLUSIONS: Since preschool children's cognitive and functional abilities are
      still in the developmental stage, parents play a crucial role in fostering
      appropriate and safe DT use. It is suggested that parents practice a combination
      of restrictive, instructive and co-using approaches, rather than a predominately
      restrictive approach, to facilitate their child's growth and development. Further
      studies are needed to explore the parent-child relationship and parents' self
      efficacy when managing the parent-child DT use, to develop strategies to guide
      children in healthy DT use.

PMID- 24887102
TI  - Tissue-specific transcript profiling for ABC transporters in the sequestering
      larvae of the phytophagous leaf beetle Chrysomela populi.
AB  - BACKGROUND: Insects evolved ingenious adaptations to use extraordinary food
      sources. Particularly, the diet of herbivores enriched with noxious plant
      secondary metabolites requires detoxification mechanisms. Sequestration, which
      involves the uptake, transfer, and concentration of occasionally modified
      phytochemicals into specialized tissues or hemolymph, is one of the most
      successful detoxification strategies found in most insect orders. Due to the
      ability of ATP-binding cassette (ABC) carriers to transport a wide range of
      molecules including phytochemicals and xenobiotics, it is highly likely that they
      play a role in this sequestration process. To shed light on the role of ABC
      proteins in sequestration, we describe an inventory of putative ABC transporters
      in various tissues in the sequestering juvenile poplar leaf beetle, Chrysomela
      populi. RESULTS: In the transcriptome of C. populi, we predicted 65 ABC
      transporters. To link the proteins with a possible function, we performed
      comparative phylogenetic analyses with ABC transporters of other insects and of
      humans. While tissue-specific profiling of each ABC transporter subfamily
      suggests that ABCB, C and G influence the plant metabolite absorption in the gut,
      ABCC with 14 members is the preferred subfamily responsible for the excretion of
      these metabolites via Malpighian tubules. Moreover, salicin, which is sequestered
      from poplar plants, is translocated into the defensive glands for further
      deterrent production. In these glands and among all identified ABC transporters,
      an exceptionally high transcript level was observed only for Cpabc35 (Cpmrp).
      RNAi revealed the deficiency of other ABC pumps to compensate the function of
      CpABC35, demonstrating its key role during sequestration. CONCLUSION: We provide
      the first comprehensive phylogenetic study of the ABC family in a phytophagous
      beetle species. RNA-seq data from different larval tissues propose the importance
      of ABC pumps to achieve a homeostasis of plant-derived compounds and offer a
      basis for future analyses of their physiological function in sequestration
      processes.

PMID- 24887106
TI  - Exercise training during normobaric hypoxic confinement does not alter hormonal
      appetite regulation.
AB  - BACKGROUND: Both exposure to hypoxia and exercise training have the potential to
      modulate appetite and induce beneficial metabolic adaptations. The purpose of
      this study was to determine whether daily moderate exercise training performed
      during a 10-day exposure to normobaric hypoxia alters hormonal appetite
      regulation and augments metabolic health. METHODS: Fourteen healthy, male
      participants underwent a 10-day hypoxic confinement at ~ 4000 m simulated
      altitude (FIO2 = 0.139 +/- 0.003%) either combined with daily moderate intensity
      exercise (Exercise group; N = 8, Age = 25.8 +/- 2.4 yrs, BMI = 22.9 +/- 1.2 kg .
      m(-2)) or without any exercise (Sedentary group; N = 6 Age = 24.8 +/- 3.1 yrs,
      BMI = 22.3 +/- 2.5 kg . m(-2)). A meal tolerance test was performed before (Pre)
      and after the confinement (Post) to quantify fasting and postp randial
      concentrations of selected appetite-related hormones and metabolic risk markers.
      13C-Glucose was dissolved in the test meal and 13CO2 determined in breath
      samples. Perceived appetite ratings were obtained throughout the meal tolerance
      tests. RESULTS: While body mass decreased in both groups (-1.4 kg; p = 0.01)
      following the confinement, whole body fat mass was only reduced in the Exercise
      group (-1.5 kg; p = 0.01). At Post, postprandial serum insulin was reduced in the
      Sedentary group (-49%; p = 0.01) and postprandial plasma glucose in the Exercise
      group (-19%; p = 0.03). Fasting serum total cholesterol levels were reduced (
      12%; p = 0.01) at Post in the Exercise group only, secondary to low-density
      lipoprotein cholesterol reduction (-16%; p = 0.01). No differences between groups
      or testing periods were noted in fasting and/or postprandial concentrations of
      total ghrelin, peptide YY, and glucagon-like peptide-1, leptin, adiponectin,
      expired 13CO2 as well as perceived appetite ratings (p>0.05). CONCLUSION: These
      findings suggest that performing daily moderate intensity exercise training
      during continuous hypoxic exposure does not alter hormonal appetite regulation
      but can improve the lipid profile in healthy young males.

PMID- 24887107
TI  - The contribution of social networks to the health and self-management of patients
      with long-term conditions: a longitudinal study.
AB  - Evidence for the effectiveness of patient education programmes in changing
      individual self-management behaviour is equivocal. More distal elements of
      personal social relationships and the availability of social capital at the
      community level may be key to the mobilisation of resources needed for long-term
      condition self-management to be effective. AIM: To determine how the social
      networks of people with long-term conditions (diabetes and heart disease) are
      associated with health-related outcomes and changes in outcomes over time.
      METHODS: Patients with chronic heart disease (CHD) or diabetes (n = 300) randomly
      selected from the disease registers of 19 GP practices in the North West of
      England. Data on personal social networks collected using a postal questionnaire,
      alongside face-to-face interviewing. Follow-up at 12 months via postal
      questionnaire using a self-report grid for network members identified at
      baseline. ANALYSIS: Multiple regression analysis of relationships between health
      status, self-management and health-economics outcomes, and characteristics of
      patients' social networks. RESULTS: Findings indicated that: (1) social
      involvement with a wider variety of people and groups supports personal self
      management and physical and mental well-being; (2) support work undertaken by
      personal networks expands in accordance with health needs helping people to cope
      with their condition; (3) network support substitutes for formal care and can
      produce substantial saving in traditional health service utilisation costs.
      Health service costs were significantly (p<0.01) reduced for patients receiving
      greater levels of illness work through their networks. CONCLUSIONS: Support for
      self-management which achieves desirable policy outcomes should be construed less
      as an individualised set of actions and behaviour and more as a social network
      phenomenon. This study shows the need for a greater focus on harnessing and
      sustaining the capacity of networks and the importance of social involvement with
      community groups and resources for producing a more desirable and cost-effective
      way of supporting long term illness management.

PMID- 24887109
TI  - Compound-specific delta15N amino acid measurements in littoral mussels in the
      California upwelling ecosystem: a new approach to generating baseline delta15N
      Isoscapes for coastal ecosystems.
AB  - We explored delta(15)N compound-specific amino acid isotope data (CSI-AA) in
      filter-feeding intertidal mussels (Mytilus californianus) as a new approach to
      construct integrated isoscapes of coastal primary production. We examined spatial
      delta(15)N gradients in the California Upwelling Ecosystem (CUE), determining
      bulk delta(15)N values of mussel tissue from 28 sites between Port Orford, Oregon
      and La Jolla, California, and applying CSI-AA at selected sites to decouple
      trophic effects from isotopic values at the base of the food web. Bulk delta(15)N
      values showed a strong linear trend with latitude, increasing from North to South
      (from ~ 70/00 to ~ 120/00, R(2) = 0.759). In contrast, CSI-AA trophic position
      estimates showed no correlation with latitude. The delta(15)N trend is therefore
      most consistent with a baseline delta(15)N gradient, likely due to the mixing of
      two source waters: low delta(15)N nitrate from the southward flowing surface
      California Current, and the northward transport of the California Undercurrent
      (CUC), with (15)N-enriched nitrate. This interpretation is strongly supported by
      a similar linear gradient in delta(15)N values of phenylalanine (delta(15)NPhe),
      the best AA proxy for baseline delta(15)N values. We hypothesize delta(15)N(Phe)
      values in intertidal mussels can approximate annual integrated delta(15)N values
      of coastal phytoplankton primary production. We therefore used delta(15)N(Phe)
      values to generate the first compound-specific nitrogen isoscape for the coastal
      Northeast Pacific, which indicates a remarkably linear gradient in coastal
      primary production delta(15)N values. We propose that delta(15)N(Phe) isoscapes
      derived from filter feeders can directly characterize baseline delta(15)N values
      across major biochemical provinces, with potential applications for understanding
      migratory and feeding patterns of top predators, monitoring effects of climate
      change, and study of paleo- archives.

PMID- 24887112
TI  - Respiratory modulation of muscle sympathetic nerve activity in obstructive sleep
      apnoea.
AB  - Obstructive sleep apnoea (OSA) is associated with elevated muscle sympathetic
      nerve activity (MSNA) during normoxic daytime wakefulness, leading to
      hypertension. We tested the hypothesis that respiratory-sympathetic coupling,
      postulated to be the underlying cause of neurogenic hypertension, is increased in
      OSA. Muscle sympathetic nerve activity, blood pressure, ECG and respiration were
      recorded in 21 normotensive control subjects and 21 newly diagnosed patients with
      OSA before and after 6 and 12 months of treatment with continuous positive airway
      pressure. Muscle sympathetic nerve activity was recorded via tungsten
      microelectrodes inserted percutaneously into the peroneal nerve. Cardiac and
      respiratory modulation of MSNA was quantified from the cross-correlation
      histograms constructed between the sympathetic spikes and either ECG or
      respiration. Muscle sympathetic nerve activity was significantly elevated in
      newly diagnosed OSA patients compared with control subjects (53 +/- 2 versus 28
      +/- 2 bursts min-1). There was a significant fall in MSNA after 6 months of
      continuous positive airway pressure (37 +/- 2 bursts min-1), with no further
      change after 12 months (37 +/- 2 bursts min-1). There were no significant
      differences in the magnitude of respiratory modulation of MSNA between the OSA
      patients and control subjects (40 +/- 3.1 versus 39 +/- 3.4%). However, when
      considering the normalized temporal profile there were changes in the respiratory
      patterning of MSNA in OSA, with more activity occurring in postinspiration and
      less in inspiration and expiration. This was largely reversed following long-term
      continuous positive airway pressure.

PMID- 24887110
TI  - Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.
AB  - Age-related hearing loss (presbycusis) is a common human disorder, affecting one
      in three Americans aged 60 and over. Previous studies have shown that
      presbyacusis is associated with a loss of non-sensory cells in the cochlear
      lateral wall. Sox10 is a transcription factor crucial to the development and
      maintenance of neural crest-derived cells including some non-sensory cell types
      in the cochlea. Mutations of the Sox10 gene are known to cause various
      combinations of hearing loss and pigmentation defects in humans. This study
      investigated the potential relationship between Sox10 gene expression and
      pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human
      temporal bones from older donors. Cochlear tissues prepared from young adult (1-3
      month-old) and aged (2-2.5 year-old) mice, and human temporal bone donors were
      examined using quantitative immunohistochemical analysis and transmission
      electron microscopy. Cells expressing Sox10 were present in the stria vascularis,
      outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+) cell
      types included marginal and intermediate cells and outer sulcus cells, including
      those that border the scala media and those extending into root processes (root
      cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a
      significant decrease in the number of Sox10(+) marginal cells and outer sulcus
      cells in aged mice. Electron microscopic evaluation revealed degenerative
      alterations in the surviving Sox10(+) cells in aged mice. Strial marginal cells
      in human cochleas from donors aged 87 and older showed only weak immunostaining
      for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+) cells in
      both mouse and human aged ears suggests an important role of Sox10 in the
      maintenance of structural and functional integrity of the lateral wall. A loss of
      Sox10(+) cells may also be associated with a decline in the repair capabilities
      of non-sensory cells in the aged ear.

PMID- 24887111
TI  - Sex differences in outcomes of methadone maintenance treatment for opioid
      addiction: a systematic review protocol.
AB  - BACKGROUND: Use of methadone for the treatment of opioid addiction is an
      effective harm-reduction approach, although variability in treatment outcomes
      among individuals has been reported. Men and women with opioid addiction have
      been known to differ in factors such as opioid use patterns and characteristics
      at treatment entry; however, little has been reported about differences in
      methadone treatment outcomes between men and women. Therefore, we present a
      protocol for a systematic review which aims to provide a summary of existing
      literature on sex differences in outcomes of methadone treatment for opioid
      addiction. METHODS/DESIGN: Electronic search of PubMed/MEDLINE, EMBASE, PsycINFO,
      and CINAHL databases will be conducted using a priori defined search strategy.
      Two authors (MB and BBD) will independently screen potential articles for
      eligibility using pre-determined inclusion and exclusion criteria and extract key
      information using a data extraction form designed for this study. Discrepancies
      will be resolved using a third party (ZS). The primary outcome will be sex
      differences in response to treatment defined as abstinence from illicit opioid
      use. We will also assess sex differences in treatment outcomes including
      treatment retention, remission status post-treatment, polysubstance abuse,
      methadone dose, drug-related adverse events, health status, psychological status,
      mortality, criminal activity, high risk sexual behavior, social
      support/relations, and employment. A meta-analysis will be conducted if possible;
      risk of bias and overall quality of evidence will be assessed to determine
      confidence in the estimates. DISCUSSION: We anticipate that this review will
      highlight how men and women differ in methadone treatment outcomes and allow us
      to generate conclusions that can be applied to treatment in a clinical setting.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013006549.

PMID- 24887113
TI  - The human carotid body releases acetylcholine, ATP and cytokines during hypoxia.
AB  - Studies on experimental animals established that the carotid bodies are sensory
      organs for detecting arterial blood O2 levels and that the ensuing chemosensory
      reflex is a major regulator of cardiorespiratory functions during hypoxia.
      However, little information is available on the human carotid body responses to
      hypoxia. The present study was performed on human carotid bodies obtained from
      surgical patients undergoing elective head and neck cancer surgery. Our results
      show that exposing carotid body slices to hypoxia for a period as brief as 5 min
      markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia
      for 1 h induces an increased release of interleukin (IL)-1beta, IL-4, IL-6, IL-8
      and IL-10. Immunohistochemical analysis revealed that type 1 cells of the human
      carotid body express an array of cytokine receptors as well as hypoxia-inducible
      factor-1alpha and hypoxia-inducible factor-2alpha. Taken together, these results
      demonstrate that ACh and ATP are released from the human carotid body in response
      to hypoxia, suggesting that these neurotransmitters, as in several experimental
      animal models, play a role in hypoxic signalling also in the human carotid body.
      The finding that the human carotid body releases cytokines in response to hypoxia
      adds to the growing body of information suggesting that the carotid body may play
      a role in detecting inflammation, providing a link between the immune system and
      the nervous system.

PMID- 24887114
TI  - AGTR2 gene polymorphism is associated with muscle fibre composition, athletic
      status and aerobic performance.
AB  - Muscle fibre type is a heritable trait and can partly predict athletic success.
      It has been proposed that polymorphisms of genes involved in the regulation of
      muscle fibre characteristics may predispose the muscle precursor cells of a given
      individual to be predominantly fast or slow. In the present study, we examined
      the association between 15 candidate gene polymorphisms and muscle fibre type
      composition of the vastus lateralis muscle in 55 physically active, healthy men.
      We found that rs11091046 C allele carriers of the angiotensin II type 2 receptor
      gene (AGTR2; involved in skeletal muscle development, metabolism and circulatory
      homeostasis) had a significantly higher percentage of slow-twitch fibres than A
      allele carriers [54.2 (11.1) versus 45.2 (10.2)%; P = 0.003]. These data indicate
      that 15.2% of the variation in muscle fibre composition of the vastus lateralis
      muscle can be explained by the AGTR2 genotype. Next, we investigated the
      frequencies of the AGTR2 alleles in 2178 Caucasian athletes and 1220 control
      subjects. The frequency of the AGTR2 C allele was significantly higher in male
      and female endurance athletes compared with power athletes (males, 62.7 versus
      51.7%, P = 0.0038; females, 56.6 versus 48.1%, P = 0.0169) and control subjects
      (males, 62.7 versus 51.0%, P = 0.0006; elite female athletes, 65.1 versus 55.2%,
      P = 0.0488). Furthermore, the frequency of the AGTR2 A allele was significantly
      over-represented in female power athletes (51.9%) in comparison to control
      subjects (44.8%, P = 0.0069). We also found that relative maximal oxygen
      consumption was significantly greater in male endurance athletes with the AGTR2 C
      allele compared with AGTR2 A allele carriers [n = 28; 62.3 (4.4) versus 57.4
      (6.0) ml min(-1) kg(-1); P = 0.0197]. Taken together, these results demonstrate
      that the AGTR2 gene C allele is associated with an increased proportion of slow
      twitch muscle fibres, endurance athlete status and aerobic performance, while the
      A allele is associated with a higher percentage of fast-twitch fibres and power
      oriented disciplines.

PMID- 24887115
TI  - alpha-Calcitonin gene related peptide (alpha-CGRP) mediated lipid mobilization in
      3T3-L1 adipocytes.
AB  - The neuropeptide, alpha-calcitonin gene-related peptide (alpha-CGRP), is
      expressed from sensory nerves that innervate fat. However, how alpha-CGRP may act
      in adipose tissue is unclear. Using 3T3-L1 adipocytes we observed that rat alpha
      CGRP (ralpha-CGRP) evoked either a biphasic or monophasic reduction in
      intracellular free fatty acid (FFA) content. cAMP production was always
      monophasic and occurred when FFA responses were absent. Taken together with the
      observed potencies, these findings suggest that adipose tissue is a physiological
      target for alpha-CGRP. However, uncoupling of the FFA and CGRP-signaling
      responses with increasing passage number limits 3T3-L1 adipocytes as a suitable
      cellular model. 

PMID- 24887116
TI  - Synthesis and characterization of a novel hybrid material as amphoteric ion
      exchanger for simultaneous removal of cations and anions.
AB  - A new hybrid chelating ion exchanger zirconium diethylene triamine (ZrD) has been
      synthesized by a simple sol-gel route using inexpensive and easily available
      chemicals. ZrD has been characterized for elemental analysis (ICP-AES, CHN
      analysis), TGA, FTIR, X-ray diffraction, SEM and EDX. Physical and ion exchange
      characteristics as well as chemical stability of the material in various media
      have been studied. Structural determination reveals that ZrD exhibits amphoteric
      character. Anion exchange capacity (AEC) for Cl(-), Br(-), Cr2O7(2-), F(-) and
      AsO4(3-) has been determined. Cations are exchanged through chelation where
      coordinating sites are offered by nitrogen atoms present in the amine groups of
      ZrD. Distribution coefficient Kd for Co(2+), Ni(2+), Cu(2+), Zn(2+) (transition
      metal ions) and Hg(2+), Cd(2+), Pb(2+) (heavy metal ions) has been evaluated by
      batch equilibration techniques in aqueous and various electrolyte
      media/concentrations. Based on alpha the separation factor, a few binary
      separations have been performed on a chromatographic column packed with ZrD. The
      amphoteric behaviour of ZrD has been demonstrated by simultaneous exchange of
      Cu(2+) and Cl(-) in CuCl2. A study on the regeneration and reuse of ZrD indicates
      that it is effective upto four cycles without much decline in performance. 

PMID- 24887117
TI  - Gas/solid particulate phthalic esters (PAEs) in Masson pine (Pinus massoniana L.)
      needles and rhizosphere surface soils.
AB  - Phthalic acid esters (PAEs) are used in many branches of industry and are
      produced in huge amounts throughout the world. An investigation on particulate-
      and gas-phase distribution of PAEs has been conducted between January 2011 and
      December 2012 in Nanjing (China). Masson pine (Pinus massoniana L.) needles and
      rhizosphere surface soils were sampled from urban to suburban/remote sites, to
      investigate the pine needle/soil distribution of PAEs. The results showed that
      the average total PAE concentration (gas+particle) was 97.0ngm(-3). The six PAE
      congeners considered predominantly existed in the gas phase and the average
      contribution of gas phase to total PAEs ranged from 75.0% to 89.1%. The PAE
      concentrations in rhizosphere soils and pine needles were positively correlated
      with their particulate- and gas-phase concentrations, respectively, which
      suggested that surface soils accumulated PAEs mainly through gravity deposition
      of particles and pine needle stomata absorbed PAEs mainly from the gas phase. The
      gas/particle partitioning (KP) and soil-pine needle ratio (Rs/n) were determined.
      Experimentally determined KP values correlated well with the subcooled liquid
      vapor pressures (PL). A set of interesting relationships of logRs/n-logKP-logPL
      was employed to explain the experimental findings of PAEs deposition to surface
      soils and to needles. This data set offered a unique perspective into the
      influence that Rs/n played in KP and correlated with PL. 

PMID- 24887118
TI  - A comprehensive evaluation of the influence of air combustion and oxy-fuel
      combustion flue gas constituents on Hg(0) re-emission in WFGD systems.
AB  - This paper evaluates the influence of the main constituents of flue gases from
      coal combustion (CO2, O2, N2 and water vapor), in air and oxy-fuel combustion
      conditions on the re-emission of Hg(0) in wet scrubbers. It was observed that the
      concentration of water vapor does not affect the re-emission of mercury, whereas
      O2 and CO2 have a notable influence. High concentrations of O2 in the flue gas
      prevent the re-emission of Hg(0) due to the reaction of oxygen with the metals
      present in low oxidation states. High concentrations of CO2, which cause a
      decrease in the pH and the redox potential of gypsum slurries, reduce the amount
      of Hg(0) that is re-emitted. As a consequence, the high content of CO2 in oxy
      fuel combustion may decrease the re-emission of Hg(0) due to the solubility of
      CO2 in the suspension and the decrease in the pH. It was also found that O2
      affects the stabilization of Hg(2+) species in gypsum slurries. The results of
      this study confirm that the amount of metals present in limestone as well as the
      redox potential and pH of the slurries in wet desulphurization plants need to be
      strictly controlled to reduce Hg(0) re-emissions from power plants operating
      under oxy-fuel combustion conditions. 

PMID- 24887119
TI  - Effect of industrial residue combinations on availability of elements.
AB  - Industrial residues, such as fly ashes and biosolids, contain elements (e.g., N,
      P, K, S, Ca and Zn) that make them a viable alternative for synthetic fertilizers
      in forestry and agriculture. However, the use of these materials is often limited
      due to the presence of potentially toxic substances. It is therefore necessary to
      assess and, when warranted, modify the chemical and physical form of these and
      similar waste materials before any advantages are taken of their beneficial
      properties. Biofuel fly ash, municipal solid waste incineration (MSWI) fly ash,
      biosolids, peat, peat residues and gypsum board waste were combined in various
      proportions, and this resulted in increased leaching of N, P, S, Cu and Mn, but
      decreased leaching of Ca, K, Mg, Cr, Fe, Ni, Zn, Al, As and Pb. Chemical
      fractionation revealed that elements Ca, K, Mg, S and Mn were predominantly
      exchangeable, while the rest of the elements were less mobile. Cadmium was mostly
      exchangeable in MSWI fly ash, but less mobile in biofuel fly ash mixtures.
      Recycling of MSWI fly ash in the mixtures with fertilizers is considerably less
      attractive, due to the high levels of salts and exchangeable Cd. 

PMID- 24887120
TI  - Degradation of C. I. Acid Orange 7 in aqueous solution by a novel
      electro/Fe3O4/PDS process.
AB  - The decolorization of C. I. Acid Orange 7 (AO7) in aqueous solution by Fe3O4
      activated peroxydisulfate (PDS) oxidation in an electrochemical reactor
      (EC/Fe3O4/PDS process) was performed in this study. Various parameters were
      investigated to optimize the process, including initial pH, current density, PDS
      concentration and Fe3O4 dosage. The stability of Fe3O4 particles was observed by
      recycle experiments. The X-ray photoelectron spectroscopy (XPS) was applied to
      investigate the surface properties of Fe3O4 before and after reaction. GC-MS
      analysis was employed to identify the intermediate products and a plausible
      degradation pathway of AO7 was proposed. The change of acute toxicity during the
      treatment was investigated by activated sludge inhibition test. The TOC removal
      efficiency was 30.0% in a 90min reaction. 

PMID- 24887121
TI  - A co-confined carbonization approach to aligned nitrogen-doped mesoporous carbon
      nanofibers and its application as an adsorbent.
AB  - Nitrogen-doped carbon nanofibers (MCNFs) with an aligned mesoporous structure
      were synthesized by a co-confined carbonization method using anodic aluminum
      oxide (AAO) membrane and tetraethylorthosilicate (TEOS) as co-confined templates
      and ionic liquids as the precursor. The as-synthesized MCNFs with the diameter of
      80-120nm possessed a bulk nitrogen content of 5.3wt% and bimodal mesoporous
      structure. The nitrogen atoms were mostly bound to the graphitic network in two
      forms, i.e. pyridinic and pyrrolic nitrogen, providing adsorption sites for
      acidic gases like SO2 and CO2. Cyclic experiments revealed a considerable
      stability of MCNFs over 20 runs of SO2 adsorption and 15 runs for CO2 adsorption.
      The MCNFs also have a preferable adsorption performance for Cd(2+). 

PMID- 24887122
TI  - Construction of a technique plan repository and evaluation system based on AHP
      group decision-making for emergency treatment and disposal in chemical pollution
      accidents.
AB  - The environmental pollution resulting from chemical accidents has caused
      increasingly serious concerns. Therefore, it is very important to be able to
      determine in advance the appropriate emergency treatment and disposal technology
      for different types of chemical accidents. However, the formulation of an
      emergency plan for chemical pollution accidents is considerably difficult due to
      the substantial uncertainty and complexity of such accidents. This paper explains
      how the event tree method was used to create 54 different scenarios for chemical
      pollution accidents, based on the polluted medium, dangerous characteristics and
      properties of chemicals involved. For each type of chemical accident, feasible
      emergency treatment and disposal technology schemes were established, considering
      the areas of pollution source control, pollutant non-proliferation, contaminant
      elimination and waste disposal. Meanwhile, in order to obtain the optimum
      emergency disposal technology schemes as soon as the chemical pollution accident
      occurs from the plan repository, the technique evaluation index system was
      developed based on group decision-improved analytical hierarchy process (AHP),
      and has been tested by using a sudden aniline pollution accident that occurred in
      a river in December 2012. 

PMID- 24887123
TI  - Molybdenum disulfide nanoflower-chitosan-Au nanoparticles composites based
      electrochemical sensing platform for bisphenol A determination.
AB  - Two-dimensional transition metal dichalcogenide are attracting increasing
      attention in electrochemical sensing due to their unique electronic properties.
      In this work, flower-like molybdenum disulfide (MoS2) was prepared by a simple
      hydrothermal method. The scanning electron microscopy and transmission electron
      microscopy images showed the MoS2 nanoflower had sizes with diameter of about
      200nm and was constructed with many irregular sheets as a petal-like structure
      with thickness of several nanometers. A novel electrochemical sensor was
      constructed for the determination of bisphenol A (BPA) based on MoS2 and chitosan
      gold nanoparticles composites modified electrode. The sensor showed an efficient
      electrocatalytic role for the oxidation of BPA, and the oxidation overpotentials
      of BPA decreased significantly and the peak current increased greatly compared
      with bare GCE and other modified electrode. A good linear relationship between
      the oxidation peak current and BPA concentration was obtained in the range from
      0.05 to 100MUM with a detection limit of 5.0*10(-9)M (S/N=3). The developed
      sensor exhibited high sensitivity and long-term stability, and it was
      successfully applied for the determination of BPA in different samples. This work
      indicated MoS2 nanoflowers were promising in electrochemical sensing and
      catalytic applications. 

PMID- 24887125
TI  - Defluoridation using biomimetically synthesized nano zirconium chitosan
      composite: kinetic and equilibrium studies.
AB  - The present study reports a novel approach for synthesis of Zr nanoparticles
      using aqueous extract of Aloe vera. Resulting nanoparticles were embedded into
      chitosan biopolymer and termed as CNZr composite. The composite was subjected to
      detailed adsorption studies for removal of fluoride from aqueous solution. The
      synthesized Zr nanoparticles showed UV-vis absorption peak at 420nm. TEM result
      showed the formation of polydispersed, nanoparticles ranging from 18nm to 42nm.
      SAED and XRD analysis suggested an fcc (face centered cubic) Zr crystallites.
      EDAX analysis suggested that Zr was an integral component of synthesized
      nanoparticles. FT-IR study indicated that functional group like NH, CO, CN and CC
      were involved in particle formation. The adsorption of fluoride on to CNZr
      composite worked well at pH 7.0, where ~99% of fluoride was found to be adsorbed
      on adsorbent. Langmuir isotherm model best fitted the equilibrium data since it
      presented higher R(2) value than Freundlich model. In comparison to pseudo-first
      order kinetic model, the pseudo-second order model could explain adsorption
      kinetic behavior of F(-) onto CNZr composite satisfactorily with a good
      correlation coefficient. The present study revealed that CNZr composite may work
      as an effective tool for removal of fluoride from contaminated water. 

PMID- 24887124
TI  - Prediction of the thermal decomposition of organic peroxides by validated QSPR
      models.
AB  - Organic peroxides are unstable chemicals which can easily decompose and may lead
      to explosion. Such a process can be characterized by physico-chemical parameters
      such as heat and temperature of decomposition, whose determination is crucial to
      manage related hazards. These thermal stability properties are also required
      within many regulatory frameworks related to chemicals in order to assess their
      hazardous properties. In this work, new quantitative structure-property
      relationships (QSPR) models were developed to predict accurately the thermal
      stability of organic peroxides from their molecular structure respecting the OECD
      guidelines for regulatory acceptability of QSPRs. Based on the acquisition of 38
      reference experimental data using DSC (differential scanning calorimetry)
      apparatus in homogenous experimental conditions, multi-linear models were derived
      for the prediction of the decomposition heat and the onset temperature using
      different types of molecular descriptors. Models were tested by internal and
      external validation tests and their applicability domains were defined and
      analyzed. Being rigorously validated, they presented the best performances in
      terms of fitting, robustness and predictive power and the descriptors used in
      these models were linked to the peroxide bond whose breaking represents the main
      decomposition mechanism of organic peroxides. 

PMID- 24887126
TI  - In-situ determination of metallic variation and multi-association in single
      particles by combining synchrotron microprobe, sequential chemical extraction and
      multivariate statistical analysis.
AB  - Due to the heterogeneity of metal distribution, it is challenging to identify the
      speciation, source and fate of metals in solid samples at micro scales. To
      overcome these challenges single particles of air pollution control residues were
      detected in situ by synchrotron microprobe after each step of chemical extraction
      and analyzed by multivariate statistical analysis. Results showed that Pb, Cu and
      Zn co-existed as acid soluble fractions during chemical extraction, regardless of
      their individual distribution as chlorides or oxides in the raw particles.
      Besides the forms of Fe2O3, MnO2 and FeCr2O4, Fe, Mn, Cr and Ni were closely
      associated with each other, mainly as reducible fractions. In addition, the two
      groups of metals had interrelations with the Si-containing insoluble matrix. The
      binding could not be directly detected by micro-X-ray diffraction (MU-XRD) and
      XRD, suggesting their partial existence as amorphous forms or in the solid
      solution. The combined method on single particles can effectively determine
      metallic multi-associations and various extraction behaviors that could not be
      identified by XRD, MU-XRD or X-ray absorption spectroscopy. The results are
      useful for further source identification and migration tracing of heavy metals. 

PMID- 24887127
TI  - Field determination and QSPR prediction of equilibrium-status soil/vegetation
      partition coefficient of PCDD/Fs.
AB  - Characterizing pseudo equilibrium-status soil/vegetation partition coefficient
      KSV, the quotient of respective concentrations in soil and vegetation of a
      certain substance at remote background areas, is essential in ecological risk
      assessment, however few previous attempts have been made for field determination
      and developing validated and reproducible structure-based estimates. In this
      study, KSV was calculated based on measurements of seventeen 2,3,7,8-substituted
      PCDD/F congeners in soil and moss (Dicranum angustum), and rouzi grass
      (Thylacospermum caespitosum) of two background sites, Ny-Alesund of the Arctic
      and Zhangmu-Nyalam region of the Tibet Plateau, respectively. By both fugacity
      modeling and stepwise regression of field data, the air-water partition
      coefficient (KAW) and aqueous solubility (SW) were identified as the influential
      physicochemical properties. Furthermore, validated quantitative structure
      property relationship (QSPR) model was developed to extrapolate the KSV
      prediction to all 210 PCDD/F congeners. Molecular polarizability, molecular size
      and molecular energy demonstrated leading effects on KSV. 

PMID- 24887128
TI  - Hexane abatement and spore emission control in a fungal biofilter-photoreactor
      hybrid unit.
AB  - The performance of a fungal perlite-based biofilter coupled to a post-treatment
      photoreactor was evaluated over 234 days in terms of n-hexane removal, emission
      and deactivation of fungal spores. The biofilter and photoreactor were operated
      at gas residence times of 1.20 and 0.14min, respectively, and a hexane loading
      rate of 115+/-5gm(-3)h(-1). Steady n-hexane elimination capacities of 30-40gm(
      3)h(-1) were achieved, concomitantly with pollutant mineralization efficiencies
      of 60-90%. No significant influence of biofilter irrigation frequency or
      irrigation nitrogen concentration on hexane abatement was recorded. Photolysis
      did not support an efficient hexane post-treatment likely due to the short EBRT
      applied in the photoreactor, while overall hexane removal and mineralization
      enhancements of 25% were recorded when the irradiated photoreactor was packed
      with ZnO-impregnated perlite. However, a rapid catalyst deactivation was
      observed, which required a periodic reactivation every 48h. Biofilter irrigation
      every 3 days supported fungal spore emissions at concentrations ranging from
      2.4*10(3) to 9.0*10(4)CFUm(-3). Finally, spore deactivation efficiencies of ~98%
      were recorded for the photolytic and photocatalytic post-treatment processes.
      This study confirmed the potential of photo-assisted post-treatment processes to
      mitigate the emission of hazardous fungal spores and boost the abatement
      performance of biotechnologies. 

PMID- 24887130
TI  - History of anaesthesia: Datex. A Finnish success story in anaesthesia monitoring.

PMID- 24887129
TI  - Chronic macrophage migration inhibitory factor exposure induces mesenchymal
      epithelial transition and promotes gastric and colon cancers.
AB  - Macrophage Migration Inhibitory Factor (MIF) is an inflammatory cytokine that is
      highly produced in gastrointestinal cancers. Since chronic inflammation is a risk
      factor for tumorigenesis in these cancers, in this study, the role of MIF in pro
      tumorigenic events was examined. MIF and its receptor, CD74, were examined in
      gastric and colon tumors and found to be increased in most tumors with
      significantly higher expression in tumors from patients with lymph node
      metastasis. MIF was also found to be highly produced by cancer associated
      fibroblasts isolated from human tumors compared to fibroblasts from matched
      normal tissues from uninvolved areas. Fibroblast-produced MIF highly increased GI
      cancer cell proliferation, which was decreased upon neutralizing MIF or CD74.
      Chronic MIF treatment led to sustained proliferation and signaling events in non
      transformed GI fibroblast cells, which was maintained upon removing MIF treatment
      for 8 weeks. Additionally, chronic treatment of normal GI cells expressing
      fibroblast markers for up to 16 weeks with MIF led to a drastic decrease of
      fibroblast markers with concurrent increase of epithelial markers. Transformation
      was examined by telomerase and focus forming assays. These results suggest the
      MIF promotes mesenchymal epithelial transition, cell transformation and
      tumorigenesis in GI cancers, and thus may be an important link between chronic
      inflammation and tumorigenesis. 

PMID- 24887131
TI  - Implementing operating room management science: from the bench to the scheduling
      office.

PMID- 24887132
TI  - Two goals, one shot at survival: DeltaPCO2 and ScvO2.

PMID- 24887133
TI  - Using type IV Pearson distribution to calculate the probabilities of underrun and
      overrun of lists of multiple cases.
AB  - BACKGROUND: An efficient operating room needs both little underutilised and
      overutilised time to achieve optimal cost efficiency. The probabilities of
      underrun and overrun of lists of cases can be estimated by a well defined
      duration distribution of the lists. OBJECTIVE: To propose a method of predicting
      the probabilities of underrun and overrun of lists of cases using Type IV Pearson
      distribution to support case scheduling. DESIGN: Six years of data were
      collected. The first 5 years of data were used to fit distributions and estimate
      parameters. The data from the last year were used as testing data to validate the
      proposed methods. The percentiles of the duration distribution of lists of cases
      were calculated by Type IV Pearson distribution and t-distribution. Monte Carlo
      simulation was conducted to verify the accuracy of percentiles defined by the
      proposed methods. SETTING: Operating rooms in John D. Dingell VA Medical Center,
      United States, from January 2005 to December 2011. MAIN OUTCOME MEASURES:
      Differences between the proportion of lists of cases that were completed within
      the percentiles of the proposed duration distribution of the lists and the
      corresponding percentiles. RESULTS: Compared with the t-distribution, the
      proposed new distribution is 8.31% (0.38) more accurate on average and 14.16%
      (0.19) more accurate in calculating the probabilities at the 10th and 90th
      percentiles of the distribution, which is a major concern of operating room
      schedulers. The absolute deviations between the percentiles defined by Type IV
      Pearson distribution and those from Monte Carlo simulation varied from 0.20  min
      (0.01) to 0.43  min (0.03). Operating room schedulers can rely on the most recent
      10 cases with the same combination of surgeon and procedure(s) for distribution
      parameter estimation to plan lists of cases. Values are mean (SEM). CONCLUSION:
      The proposed Type IV Pearson distribution is more accurate than t-distribution to
      estimate the probabilities of underrun and overrun of lists of cases. However, as
      not all the individual case durations followed log-normal distributions, there
      was some deviation from the true duration distribution of the lists.

PMID- 24887134
TI  - Reply to: Association of haemoglobin levels with postoperative cardiovascular
      adverse events in patients undergoing vascular surgery.

PMID- 24887135
TI  - Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the
      type of infusion fluid: Retraction.

PMID- 24887136
TI  - Development of a magnetocardiography-based algorithm for discrimination between
      ventricular arrhythmias originating from the right ventricular outflow tract and
      those originating from the aortic sinus cusp: a pilot study.
AB  - BACKGROUND: Although several reports address characteristic 12-lead
      electrocardiographic findings of outflow tract ventricular arrhythmias (OT-VAs),
      the accuracy of electrocardiogram-based algorithms to predict the OT-VA origin is
      sometimes limited. OBJECTIVE: This study aimed to develop a magnetocardiography
      (MCG)-based algorithm using a novel adaptive spatial filter to differentiate
      between VAs originating from the aortic sinus cusp (ASC-VAs) and those
      originating from the right ventricular outflow tract (RVOT-VAs). METHODS: This
      study comprised 51 patients with an OT-VA as the target of catheter ablation. An
      algorithm was developed by correlating MCG findings with the successful ablation
      site. The arrhythmias were classified as RVOT-VAs or ASC-VAs. Three parameters
      were obtained from 3-dimensional MCG imaging: depth of the origin of the OT-VA in
      the anteroposterior direction; distance between the earliest atrial activation
      site, that is, sinus node, and the origin of the OT-VA; and orientation of the
      arrhythmia propagation at the QRS peak. The distance was indexed to the patient's
      body surface area (in mm/m2). RESULTS: Origins of ASC-VAs were significantly
      deeper (81 +/- 6 mm/m(2) vs. 68 +/- 8 mm/m(2); P < .01) and farther from the
      sinus node (55 +/- 9 mm/m2 vs. 41 +/- 9 mm/m(2); P < .01) than those of RVOT-VAs.
      ASC-VA propagation had a tendency toward rightward axis. Receiver operating
      characteristic analyses determined that the depth of the origin was the most
      powerful predictor, with a sensitivity of 90% and a specificity of 73% (area
      under the curve = 0.90; P < .01). Discriminant analysis combining all 3
      parameters revealed the accuracy of the localization to be 94%. CONCLUSION: This
      MCG-based algorithm appeared to precisely discriminate ASC-VAs from RVOT-VAs.
      Further investigation is required to validate the clinical value of this
      technique.

PMID- 24887137
TI  - Efficacy of cardiac resynchronization in acutely infarcted canine hearts with
      electromechanical dyssynchrony.
AB  - BACKGROUND: Patients with acute myocardial infarction (MI), left bundle branch
      block (LBBB), and marked left ventricular (LV) decompensation suffer from nearly
      50% early mortality. Whether cardiac resynchronization therapy (CRT) improves
      hemodynamic status in this condition is unknown. We tested CRT in this setting by
      using a canine model of delayed lateral wall (LW) activation combined with 2
      hours of coronary artery occlusion-reperfusion. OBJECTIVE: This study aimed to
      evaluate the acute hemodynamic effects of CRT during and immediately after MI.
      METHODS: Adult dogs (n = 8) underwent open-chest 2-hour mid-left anterior
      descending artery occlusion followed by 1-hour reperfusion. Four pacing modes
      were compared: right atrial pacing, pseudo-left bundle block (right ventricular
      pacing), and CRT with the LV lead positioned at either the LW (LW-CRT) or the
      peri-infarct zone (peri-infarct zone-CRT). Continuous LV pressure-volume data,
      regional segment length, and proximal left anterior descending flow rates were
      recorded. RESULTS: At baseline, both right ventricular pacing and peri-infarct
      zone CRT reduced anterior wall regional work by ~50% (vs right atrial pacing).
      During coronary occlusion, this territory became dyskinetic, and dyskinesis rose
      further with both CRT modes as compared to pseudo-LBBB. Global cardiac output,
      stroke work, and ejection fraction all still improved by 11%-23%. After
      reperfusion, both CRT modes elevated infarct zone regional work and blood flow by
      ~10% as compared to pseudo-LBBB, as well as improved global function. CONCLUSION:
      CRT improves global chamber systolic function in left ventricles with delayed LW
      activation during and after sustained coronary occlusion. It does so while
      modestly augmenting infarct zone dyskinesis during occlusion and improving
      regional function and blood flow after reperfusion. These findings support CRT in
      the setting of early post-MI dyssynchronous heart failure.

PMID- 24887140
TI  - The patient rotation.

PMID- 24887138
TI  - Heat shock protein-70 (Hsp-70) suppresses paraquat-induced neurodegeneration by
      inhibiting JNK and caspase-3 activation in Drosophila model of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative disorders
      with limited clinical interventions. A number of epidemiological as well as case
      control studies have revealed an association between pesticide exposure,
      especially of paraquat (PQ) and occurrence of PD. Hsp70, a molecular chaperone by
      function, has been shown as one of the modulators of neurological disorders.
      However, paucity of information regarding the protective role of Hsp70 on PQ
      induced PD like symptoms led us to hypothesize that modulation of hsp70
      expression in the dopaminergic neurons would improve the health of these cells.
      We took advantage of Drosophila, which is a well-established model for
      neurological research and also possesses genetic tools for easy manipulation of
      gene expression with limited ethical concern. Over-expression of hsp70 was found
      to reduce PQ-induced oxidative stress along with JNK and caspase-3 mediated
      dopaminergic neuronal cell death in exposed organism. Further, anti-apoptotic
      effect of hsp70 was shown to confer better homeostasis in the dopaminergic
      neurons of PQ-exposed organism as evidenced by their improved locomotor
      performance and survival. The study has merit in the context of human concern
      since we observed protection of dopaminergic neurons in PQ-exposed organism by
      over-expressing a human homologue of hsp70, HSPA1L, in these cells. The effect
      was parallel to that observed with Drosophila hsp70. These findings reflect the
      potential therapeutic applicability of hsp70 against PQ-induced PD like symptoms
      in an organism. 

PMID- 24887139
TI  - Adenosine deaminase activity modulation by some street drug: molecular docking
      simulation and experimental investigation.
AB  - BACKGROUND: Adenosine deaminase (ADA) is an enzyme that plays important roles in
      proliferation, maturation, function and development of the immune system. ADA
      activity may be altered by variety of substances including synthetic or natural
      products. Morphine, cocaine and their analogs exert immune suppressive activities
      by decreasing immune system function. The purpose of this study is to confirm
      that this possible effect may be modulated by interaction of these substances
      with ADA activity by experimental and computational method. METHODS: The
      structural changes in ADA have been studied in presence of cocaine,
      ethylmorphine, homatropine, morphine and thebaine by determination of ADA
      hydrolytic activity, circular dichroism and fluorescence spectroscopy in
      different concentrations. Docking study was performed to evaluate interaction
      method of test compound with ADA active site using AutoDock4 software. RESULTS:
      According to in-vitro studies all compounds inhibited ADA with different
      potencies, however thebaine activated it at concentration below 50 MUM,
      ethylmorphine inhibited ADA at 35 MUM. Moreover, fluorescence spectra patterns
      were differed from compounds based on structural resemblance which were very
      considerable for cocaine and homatropine. CONCLUSION: The results of this study
      confirms that opioids and some other stimulant drugs such as cocaine can alter
      immune function in illegal drug abusers. These findings may lead other
      investigators to develop a new class of ADA activators or inhibitors in the near
      future.

PMID- 24887141
TI  - Engineering interconnected 3D vascular networks in hydrogels using molded sodium
      alginate lattice as the sacrificial template.
AB  - Engineering 3D perfusable vascular networks in vitro and reproducing the
      physiological environment of blood vessels is very challenging for tissue
      engineering and investigation of blood vessel function. Here, we engineer
      interconnected 3D microfluidic vascular networks in hydrogels using molded sodium
      alginate lattice as sacrificial templates. The sacrificial templates are rapidly
      replicated in polydimethylsiloxane (PDMS) microfluidic chips via Ca+2
      crosslinking and then fully encapsulated in hydrogels. Interconnected channels
      with well controlled size and morphology are obtained by dissolving the monolayer
      or multilayer templates with EDTA solution. The human umbilical vein endothelial
      cells (HUVECs) are cultured on the channel linings and proliferated to form
      vascular lumens. The strong cell adhesion capability and adaptive response to
      shear stress demonstrate the excellent cytocompatibility of both the template and
      template-sacrificing process. Furthermore, the barrier function of the
      endothelial layer is characterized and the results show that a confluent
      endothelial monolayer is fully developed. Taken together, we develop a facile and
      rapid approach to engineer a vascular model that could be potentially used in
      physiological studies of vascular functions and vascular tissue engineering.

PMID- 24887142
TI  - Clustering of giant virus-DNA based on variations in local entropy.
AB  - We present a method for clustering genomic sequences based on variations in local
      entropy. We have analyzed the distributions of the block entropies of viruses and
      plant genomes. A distinct pattern for viruses and plant genomes is observed.
      These distributions, which describe the local entropic variability of the
      genomes, are used for clustering the genomes based on the Jensen-Shannon (JS)
      distances. The analysis of the JS distances between all genomes that infect the
      chlorella algae shows the host specificity of the viruses. We illustrate the
      efficacy of this entropy-based clustering technique by the segregation of plant
      and virus genomes into separate bins. 

PMID- 24887144
TI  - Rapid fabrication of hierarchically structured supramolecular nanocomposite thin
      films in one minute.
AB  - Functional nanocomposites containing nanoparticles of different chemical
      compositions may exhibit new properties to meet demands for advanced technology.
      It is imperative to simultaneously achieve hierarchical structural control and to
      develop rapid, scalable fabrication to minimize degradation of nanoparticle
      properties and for compatibility with nanomanufacturing. Here we show that the
      assembly kinetics of supramolecular nanocomposites in thin films are governed by
      the energetic cost arising from defects, the chain mobility and the activation
      energy for inter-domain diffusion. By optimizing only one parameter, the solvent
      fraction in the film, the assembly kinetics can be precisely tailored to produce
      hierarchically structured thin films of supramolecular nanocomposites in one
      minute. Moreover, the strong wavelength-dependent optical anisotropy in the
      nanocomposite highlights their potential applications for light manipulation and
      information transmission. The present study may open a new avenue in designing
      manufacture-friendly continuous processing for the fabrication of functional
      nanocomposite thin films. 

PMID- 24887143
TI  - B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and
      primary Sjogren's syndrome: the similarities and differences.
AB  - INTRODUCTION: IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune
      disease. Abnormally activated and differentiated B cells may play important
      roles. Regulatory B cells (Breg) are newly defined B cell subgroups with
      immunosuppressive functions. In this study, we investigated the differences of B
      cell subsets, the expressions of co-stimulatory molecules on B cells, and the
      function of Breg cells in patients with IgG4-RD, primary Sjogren's syndrome (pSS)
      as well as in healthy controls (HC). METHODS: Newly diagnosed IgG4-RD patients (n
      = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were
      recruited as disease and healthy controls. To analyze B cell subsets and B cell
      activity, PBMCs were surface stained and detected by flow cytometry. The function
      of Breg cells was tested by coculturing isolated CD19 + CD24(hi)CD38(hi) Breg
      cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA
      and cytometric bead array. Relationship between clinical data and laboratory
      findings were analyzed as well. RESULTS: Compared with pSS patients and HC, IgG4
      RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 +
      CD24-CD38(hi) B cell subsets were significantly higher in peripheral B cells from
      IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4
      levels. The expression of BAFF-R and CD40 on B cells was significantly lower in
      IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg
      cells from pSS patients lacked suppressive functions. CONCLUSIONS: B cells in
      patients with IgG4-RD and pSS display a variety of abnormalities, including
      disturbed B cell subpopulations, abnormal expression of key signaling molecules,
      co-stimulatory molecules, and inflammatory cytokines. In addition, a
      significantly increased B cell subset, CD19 + CD24-CD38(hi) B cells, may play an
      important role in the pathogenesis of IgG4-RD.

PMID- 24887146
TI  - Full-text publication of abstracts in emergency medicine in Denmark.
AB  - INTRODUCTION: Abstracts presented at medical conferences or scientific meetings
      should ideally be published as full-text articles in peer-reviewed journals after
      initial presentation and feedback regardless of the findings. The aim of this
      survey was to determine the publication rate of papers presented at the Danish
      Emergency Medicine Conferences in 2009, 2010 and 2011. METHODS: Abstracts
      presented at the conferences were identified and authors contacted to obtain
      publication information. A further search was conducted using relevant databases.
      RESULTS: Publication rates for the 2009 and 2010 were approximately 30% (25
      31.6%). The publication rate for the 2011 conference was 14.5% within 18 months
      with an additional 9% under review prior to publication. DISCUSSION: When
      comparing full-text publication rates from DEMC to previous international studies
      in EM Danish EM research community has similar publication rates. However, other
      more established specialties have higher publication levels. Knowledge of reasons
      for non-publication could lead to efforts to promote publication like funding;
      the possibility of discussion between authors and editors at conferences;
      "publication mentors"; and/or research courses provided by the Danish Society of
      Emergency Medicine.

PMID- 24887145
TI  - Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from
      women with preeclampsia or conditioned media from hypoxic placenta.
AB  - CONTEXT: Placenta-derived circulating factors contribute to the maternal
      endothelial dysfunction underlying preeclampsia. Endothelial colony forming cells
      (ECFC), a sub-population of endothelial progenitor cells (EPCs), are thought to
      be involved in vasculogenesis and endothelial repair. Low vitamin D
      concentrations are associated with an increased risk for preeclampsia. OBJECTIVE:
      We hypothesized that the function of human fetal ECFCs in culture would be
      suppressed by exposure to preeclampsia-related factors--preeclampsia serum or
      hypoxic placental conditioned medium--in a fashion reversed by vitamin D. DESIGN,
      SETTING, PATIENTS: ECFCs were isolated from cord blood of uncomplicated
      pregnancies and expanded in culture. Uncomplicated pregnancy villous placenta in
      explant culture were exposed to either 2% (hypoxic), 8% (normoxic) or 21%
      (hyperoxic) O2 for 48 h, after which the conditioned media (CM) was collected.
      OUTCOME MEASURES: ECFC tubule formation (Matrigel assay) and migration were
      examined in the presence of either maternal serum from preeclampsia cases or
      uncomplicated pregnancy controls, or pooled CM, in the presence or absence of
      1,25(OH)2 vitamin D3. RESULTS: 1,25(OH)2 vitamin D3 reversed the adverse effects
      of preeclampsia serum or CM from hypoxic placenta on ECFCs capillary-tube
      formation and migration. Silencing of VDR expression by VDR siRNA, VDR blockade,
      or VEGF pathway blockade reduced ECFC functional abilities. Effects of VDR or
      VEGF blockade were partially prevented by vitamin D. CONCLUSION: Vitamin D
      promotes the capillary-like tubule formation and migration of ECFCs in culture,
      minimizing the negative effects of exposure to preeclampsia-related factors.
      Further evaluation of the role of vitamin D in ECFC regulation and preeclampsia
      is warranted.

PMID- 24887147
TI  - Structural and mutagenic analysis of the RM controller protein C.Esp1396I.
AB  - Bacterial restriction-modification (RM) systems are comprised of two
      complementary enzymatic activities that prevent the establishment of foreign DNA
      in a bacterial cell: DNA methylation and DNA restriction. These two activities
      are tightly regulated to prevent over-methylation or auto-restriction. Many Type
      II RM systems employ a controller (C) protein as a transcriptional regulator for
      the endonuclease gene (and in some cases, the methyltransferase gene also). All
      high-resolution structures of C-protein/DNA-protein complexes solved to date
      relate to C.Esp1396I, from which the interactions of specific amino acid residues
      with DNA bases and/or the phosphate backbone could be observed. Here we present
      both structural and DNA binding data for a series of mutations to the key DNA
      binding residues of C.Esp1396I. Our results indicate that mutations to the
      backbone binding residues (Y37, S52) had a lesser affect on DNA binding affinity
      than mutations to those residues that bind directly to the bases (T36, R46), and
      the contributions of each side chain to the binding energies are compared. High
      resolution X-ray crystal structures of the mutant and native proteins showed that
      the fold of the proteins was unaffected by the mutations, but also revealed
      variation in the flexible loop conformations associated with DNA sequence
      recognition. Since the tyrosine residue Y37 contributes to DNA bending in the
      native complex, we have solved the structure of the Y37F mutant protein/DNA
      complex by X-ray crystallography to allow us to directly compare the structure of
      the DNA in the mutant and native complexes. 

PMID- 24887148
TI  - Cardiomyopathy in a male patient with neutropenia and growth delay.
AB  - Neutropenia encompasses a family of neutropenic disorders, both permanent and
      intermittent, ranging from severe (<500 neutrophils/mm(3)) to mild (500-1500
      neutrophils/mm(3)), which may also affect other organ systems such as the
      pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to
      life-threatening pyogenic infections whose severity is roughly inversely
      proportional to the circulating neutrophil counts.When neutropenia is detected,
      an attempt should be made to establish the etiology, and to distinguish acquired
      forms (the most frequent, including post viral neutropenia and autoimmune
      neutropenia) and congenital forms (rare disorders) that may be either isolated or
      part of a complex rare genetic disease. We report on a male patient initially
      diagnosed with isolated neutropenia who later turned out to be affected with
      Barth syndrome, a rare complex inherited disorder.

PMID- 24887149
TI  - Combined experimental and in silico approaches for exploring antiperoxidative
      potential of structurally diverse classes of antioxidants on docetaxel-induced
      lipid peroxidation using 4-HNE as the model marker.
AB  - The objective of the present work was tantamount to explain the antiperoxidative
      potential and structural requirements of twenty-eight structurally diverse
      classes of antioxidants on docetaxel-induced lipid peroxidation. Both
      experimental and computational approaches were taken to the work. The experiments
      were performed in vitro and goat liver was used as a source of lipid. 4-hydroxy-2
      nonenal was used as model marker for estimation of docetaxel-lipid interaction.
      The computational portion of the work was limited to QSAR analysis of those
      antioxidants for better understanding of the structural requirements of
      antioxidants on docetaxel-lipid interaction. The study was done with freely
      online available 2D descriptors available on PaDEL (open source). Stepwise
      regression analysis was used as chemometric tool. The experimental study showed
      the lipid peroxidation induction capacity of docetaxel. It was also noted that
      all twenty-eight antioxidants had the ability to suppress the lipid peroxidation.
      But among them butylated hydroxyl toluene showed the highest potential (-20.5%)
      and flavone showing lowest potential (-0.8%) to suppress the docetaxel-induced
      lipid peroxidation. The computational study indicates the importance of topology
      of the whole molecules, topological distances among atoms within a molecule and
      specific fragment pattern present in a molecule required for inhibition of lipid
      peroxidation. 

PMID- 24887150
TI  - Screening mammography & breast cancer mortality: meta-analysis of quasi
      experimental studies.
AB  - BACKGROUND: The magnitude of the benefit associated with screening has been
      debated. We present a meta-analysis of quasi-experimental studies on the effects
      of mammography screening. METHODS: We searched MEDLINE/PubMed and Embase for
      articles published through January 31, 2013. Studies were included if they
      reported: 1) a population-wide breast cancer screening program using mammography
      with 5+ years of data post-implementation; 2) a comparison group with equal
      access to therapies; and 3) breast cancer mortality. Studies excluded were: RCTs,
      case-control, or simulation studies. We defined quasi-experimental as studies
      that compared either geographical, historical or birth cohorts with a screening
      program to an equivalent cohort without a screening program. Meta-analyses were
      conducted in Stata using the metan command, random effects. Meta-analyses were
      conducted separately for ages screened: under 50, 50 to 69 and over 70 and
      weighted by population and person-years. RESULTS: Among 4,903 published papers
      that were retrieved, 19 studies matched eligibility criteria. Birth cohort
      studies reported a significant benefit for women screened <age 50, but not for
      women screened ages 50-69. Significant reductions in breast cancer mortality were
      observed in historical comparisons. For geographical comparisons, there was a
      significant 20% reduction in mortality for women <age 50 and a significant 21-22%
      reduction for women ages 50-69. Studies that tested the interaction of
      geographical and historical comparisons produced a pooled, significant 13-17%
      reduction in incident breast cancer mortality for women ages 50-69, but the
      effects in most individual studies were non-significant. All studies of women
      ages 70+ were non-significant. CONCLUSIONS: Mammography screening may have modest
      effects on cancer mortality between the ages of 50 and 69 and non-significant
      effects for women older than age 70. Results are consistent with meta-analyses of
      RCTs. Effects on total mortality could not be assessed because of the limited
      number of studies.

PMID- 24887153
TI  - Medical ethics and new public management in Sweden.
AB  - In order to shorten queues to healthcare, the Swedish government has introduced a
      yearly "queue billion" that is paid out to the county councils in proportion to
      how successful they are in reducing queues. However, only the queues for first
      visits are covered. Evidence has accumulated that queues for return visits have
      become longer. This affects the chronically and severely ill. Swedish physicians,
      and the Swedish Medical Association, have strongly criticized the queue billion
      and have claimed that it conflicts with medical ethics. Instead they demand that
      their professional judgments on priority setting and medical urgency be
      respected. This discussion provides an interesting illustration of some of the
      limitations of new public management and also more generally of the complicated
      relationships between medical ethics and public policy.

PMID- 24887152
TI  - TRAIL induces neutrophil apoptosis and dampens sepsis-induced organ injury in
      murine colon ascendens stent peritonitis.
AB  - TNF-related apoptosis inducing ligand (TRAIL) influences several inflammatory
      reactions by partially still unknown mechanisms. TRAIL is produced and expressed
      by several cells of the immune system. Murine Colon Ascendens Stent Peritonitis
      (CASP) represents a hyperinflammatory model of diffuse peritonitis. As we have
      shown previously, TRAIL strongly improves survival in murine CASP. This is
      accompanied by a significantly reduced infiltration of neutrophils in the
      associated lymphoid tissue. Additionally, it is known that TRAIL induces
      apoptosis in neutrophils and acceleration of neutrophil apoptosis enhances
      resolution of inflammatory reactions. In this study, we investigated the
      correlation of the protective effect of TRAIL in sepsis and its influence on
      neutrophils. We found that neutrophils infiltrating the lymphoid organs express
      the TRAIL-receptor DR5 at high density. Furthermore, we demonstrated that TRAIL
      treatment enhances apoptosis of neutrophils in the spleen, lung and liver and
      decreases organ injury during sepsis. To further examine a role for neutrophils
      in TRAIL-mediated protection in CASP, we have depleted neutrophils 24 hours prior
      to CASP. In these depleted mice, administration of TRAIL was ineffective. We
      conclude that TRAIL induces apoptosis in tissue-infiltrating neutrophils thereby
      protecting organs from sepsis-induced injury. 

PMID- 24887154
TI  - Determination of the easy axes of small ferromagnetic precipitates in a bulk
      material by combined magnetic force microscopy and electron backscatter
      diffraction techniques.
AB  - A method to determine the magnetic easy axes of micro- and nanoscopic
      ferromagnetic precipitates embedded in a bulk material is proposed and applied to
      globular cementite (Fe3C) embedded in a ferrite matrix. The method combines
      magnetic force microscopy (MFM) with electron backscattered diffraction (EBSD)
      measurements. Magnetic domain structures in globular and in lamellar cementite
      precipitates in unalloyed pearlitic steels were imaged using MFM. The domain
      structure of the precipitates was analyzed in dependency of their size, shape and
      crystallographic orientation. It was found that the magnetic moments of the
      cementite precipitates are highly geared to their crystalline axes. The combined
      MFM and EBSD studies allow the conclusion that the cementite easy direction of
      magnetization is the long [010] axis. For fine lamellae cementite the
      determination of their crystallographic orientations using electron diffraction
      techniques is very difficult. With the previous knowledge of the behavior of the
      domain structure in globular cementite, the crystalline orientations of the fine
      lamellae cementite can be estimated by simply observing the magnetic
      microstructures and the topographic profiles.

PMID- 24887155
TI  - Early fluid loading in acute respiratory distress syndrome with septic shock
      deteriorates lung aeration without impairing arterial oxygenation: a lung
      ultrasound observational study.
AB  - INTRODUCTION: The study was designed to assess the impact of fluid loading on
      lung aeration, oxygenation and hemodynamics in patients with septic shock and
      acute respiratory distress syndrome (ARDS). METHODS: During a 1-year period, a
      prospective observational study was performed in 32 patients with septic shock
      and ARDS. Cardiorespiratory parameters were measured using Swan Ganz (n = 29) or
      PiCCO catheters (n = 3). Lung aeration and regional pulmonary blood flows were
      measured using bedside transthoracic ultrasound. Measurements were performed
      before (T0), at the end of volume expansion (T1) and 40 minutes later (T2),
      consisting of 1-L of saline over 30 minutes during the first 48 h following onset
      of septic shock and ARDS. RESULTS: Lung ultrasound score increased by 23% at T2,
      from 13 at baseline to 16 (P < 0.001). Cardiac index and cardiac filling
      pressures increased significantly at T1 (P < 0.001) and returned to control
      values at T2. The increase in lung ultrasound score was statistically correlated
      with fluid loading-induced increase in cardiac index and was not associated with
      increase in pulmonary shunt or regional pulmonary blood flow. At T1, PaO2/FiO2
      significantly increased (P < 0.005) from 144 (123 to 198) to 165 (128 to 226) and
      returned to control values at T2, whereas lung ultrasound score continued to
      increase. CONCLUSIONS: Early fluid loading transitorily improves hemodynamics and
      oxygenation and worsens lung aeration. Aeration changes can be detected at the
      bedside by transthoracic lung ultrasound, which may serve as a safeguard against
      excessive fluid loading.

PMID- 24887157
TI  - A folate receptor-specific activatable probe for near-infrared fluorescence
      imaging of ovarian cancer.
AB  - We have developed a folate receptor-specific activatable probe for in vivo near
      infrared fluorescence imaging of ovarian cancer. This probe becomes highly
      fluorescent only when its linker is cleaved by a tumor-associated lysosomal
      enzyme cathepsin B after internalization into folate receptor-positive cancer
      cells. 

PMID- 24887156
TI  - Direct effects of metformin in the endometrium: a hypothetical mechanism for the
      treatment of women with PCOS and endometrial carcinoma.
AB  - Although a number of in vitro studies have demonstrated the antiproliferative,
      anti-invasive, and antimetastatic effects of metformin in multiple cancer cell
      types, its cellular and molecular mechanisms of anti-cancer action in the
      endometrium of women with polycystic ovary syndrome (PCOS) have not yet been
      fully elucidated. Organic cation transporters (OCTs) and multidrug and toxin
      extrusion proteins (MATEs) are known to be involved in metformin uptake and
      excretion in cells. In this article, we discuss the novel therapeutic
      possibilities for early-stage endometrial carcinoma (EC) in women with PCOS
      focusing on metformin, which might have a direct effect in the endometrium
      through the OCTs and MATEs. We then review the molecular mechanism(s) of the
      action of metformin in the endometrium and highlight possible mechanistic
      insights into the inhibition of cell proliferation and tumor growth and,
      ultimately, the reversal of early-stage EC into normal endometria in women with
      PCOS. 

PMID- 24887160
TI  - Commentary: race: ritual, regression, and reality.

PMID- 24887159
TI  - On the causal interpretation of race in regressions adjusting for confounding and
      mediating variables.
AB  - We consider several possible interpretations of the "effect of race" when
      regressions are run with race as an exposure variable, controlling also for
      various confounding and mediating variables. When adjustment is made for
      socioeconomic status early in a person's life, we discuss under what contexts the
      regression coefficients for race can be interpreted as corresponding to the
      extent to which a racial inequality would remain if various socioeconomic
      distributions early in life across racial groups could be equalized. When
      adjustment is also made for adult socioeconomic status, we note how the overall
      racial inequality can be decomposed into the portion that would be eliminated by
      equalizing adult socioeconomic status across racial groups and the portion of the
      inequality that would remain even if adult socioeconomic status across racial
      groups were equalized. We also discuss a stronger interpretation of the effect of
      race (stronger in terms of assumptions) involving the joint effects of race
      associated physical phenotype (eg, skin color), parental physical phenotype,
      genetic background, and cultural context when such variables are thought to be
      hypothetically manipulable and if adequate control for confounding were possible.
      We discuss some of the challenges with such an interpretation. Further discussion
      is given as to how the use of selected populations in examining racial
      disparities can additionally complicate the interpretation of the effects. 

PMID- 24887158
TI  - Non-invasive assessment of retinal alterations in mouse models of infantile and
      juvenile neuronal ceroid lipofuscinosis by spectral domain optical coherence
      tomography.
AB  - INTRODUCTION: The neuronal ceroid lipofuscinoses constitute a group of fatal
      inherited lysosomal storage diseases that manifest in profound neurodegeneration
      in the CNS. Visual impairment usually is an early symptom and selective
      degeneration of retinal neurons has been described in patients suffering from
      distinct disease subtypes. We have previously demonstrated that palmitoyl protein
      thioesterase 1 deficient (Ppt1-/-) mice, a model of the infantile disease
      subtype, exhibit progressive axonal degeneration in the optic nerve and loss of
      retinal ganglion cells, faithfully reflecting disease severity in the CNS. Here
      we performed spectral domain optical coherence tomography (OCT) in Ppt1-/- and
      ceroid lipofuscinosis neuronal 3 deficient (Cln3-/-) mice, which are models of
      infantile and juvenile neuronal ceroid lipofuscinosis, respectively, in order to
      establish a non-invasive method to assess retinal alterations and monitor disease
      severity in vivo. RESULTS: Blue laser autofluorescence imaging revealed increased
      accumulation of autofluorescent storage material in the inner retinae of 7-month
      old Ppt1-/- and of 16-month-old Cln3-/- mice in comparison with age-matched
      control littermates. Additionally, optical coherence tomography demonstrated
      reduced thickness of retinae in knockout mice in comparison with age-matched
      control littermates. High resolution scans and manual measurements allowed for
      separation of different retinal composite layers and revealed a thinning of
      layers in the inner retinae of both mouse models at distinct ages. OCT
      measurements correlated well with subsequent histological analysis of the same
      retinae. CONCLUSIONS: These results demonstrate the feasibility of OCT to assess
      neurodegenerative disease severity in mouse models of neuronal ceroid
      lipofuscinosis and might have important implications for diagnostic evaluation of
      disease progression and therapeutic efficacy in patients. Moreover, the non
      invasive method allows for longitudinal studies in experimental models, reducing
      the number of animals used for research.

PMID- 24887161
TI  - Commentary: race and sex are causes.

PMID- 24887162
TI  - Rejoinder: how to reduce racial disparities?: Upon what to intervene?

PMID- 24887163
TI  - Commentary: cities and health...let me count the ways.

PMID- 24887164
TI  - PM2.5 species: importance of accurate measurement.

PMID- 24887165
TI  - Added salt and cancer mortality: confounding by smoking.

PMID- 24887166
TI  - Mobile phones and cancer: next steps.

PMID- 24887167
TI  - Mobile phones and cancer: next steps.

PMID- 24887168
TI  - The authors respond.

PMID- 24887169
TI  - Further refinements to the organizational schema for causal effects.

PMID- 24887170
TI  - The authors respond.

PMID- 24887171
TI  - "Hotheaded": the role OF TRPV1 in brain functions.
AB  - The TRPV1 (vanilloid 1) channel is best known for its role in sensory
      transmission in the nociceptive neurons of the peripheral nervous system.
      Although first studied in the dorsal root ganglia as the receptor for capsaicin,
      TRPV1 has been recently recognized to have a broader distribution in the central
      nervous system, where it is likely to constitute an atypical neurotransmission
      system involved in several functions through modulation of both neuronal and
      glial activities. The endovanilloid-activated brain TRPV1 channels seem to be
      involved in somatosensory, motor and visceral functions. Recent studies suggested
      that TRPV1 channels also account for more complex functions, as addiction,
      anxiety, mood and cognition/learning. However, more studies are needed before the
      relevance of TRPV1 in brain activity can be clearly stated. This review
      highlights the increasing importance of TRPV1 as a regulator of brain function
      and discusses possible bases for the future development of new therapeutic
      approaches that by targeting brain TRPV1 receptors might be used for the
      treatment of several neurological disorders. 

PMID- 24887172
TI  - Investigation of continuous effect modifiers in a meta-analysis on higher versus
      lower PEEP in patients requiring mechanical ventilation--protocol of the ICEM
      study.
AB  - BACKGROUND: Categorizing an inherently continuous predictor in prognostic
      analyses raises several critical methodological issues: dependence of the
      statistical significance on the number and position of the chosen cut-point(s),
      loss of statistical power, and faulty interpretation of the results if a non
      linear association is incorrectly assumed to be linear. This also applies to a
      therapeutic context where investigators of randomized clinical trials (RCTs) are
      interested in interactions between treatment assignment and one or more
      continuous predictors. METHODS/DESIGN: Our goal is to apply the multivariable
      fractional polynomial interaction (MFPI) approach to investigate interactions
      between continuous patient baseline variables and the allocated treatment in an
      individual patient data meta-analysis of three RCTs (N = 2,299) from the
      intensive care field. For each study, MFPI will provide a continuous treatment
      effect function. Functions from each of the three studies will be averaged by a
      novel meta-analysis approach for functions. We will plot treatment effect
      functions separately for each study and also the averaged function. The averaged
      function with a related confidence interval will provide a suitable basis to
      assess whether a continuous patient characteristic modifies the treatment
      comparison and may be relevant for clinical decision-making. The compared
      interventions will be a higher or lower positive end-expiratory pressure (PEEP)
      ventilation strategy in patients requiring mechanical ventilation. The continuous
      baseline variables body mass index, PaO2/FiO2, respiratory compliance, and
      oxygenation index will be the investigated potential effect modifiers. Clinical
      outcomes for this analysis will be in-hospital mortality, time to death, time to
      unassisted breathing, and pneumothorax. DISCUSSION: This project will be the
      first meta-analysis to combine continuous treatment effect functions derived by
      the MFPI procedure separately in each of several RCTs. Such an approach requires
      individual patient data (IPD). They are available from an earlier IPD meta
      analysis using different methods for analysis. This new analysis strategy allows
      assessing whether treatment effects interact with continuous baseline patient
      characteristics and avoids categorization-based subgroup analyses. These
      interaction analyses of the present study will be exploratory in nature. However,
      they may help to foster future research using the MFPI approach to improve
      interaction analyses of continuous predictors in RCTs and IPD meta-analyses. This
      study is registered in PROSPERO (CRD42012003129).

PMID- 24887173
TI  - Age group comparability of raw accelerometer output from wrist- and hip-worn
      monitors.
AB  - PURPOSE: The study aims were to compare raw triaxial accelerometer output from
      ActiGraph GT3X+ (AG) and GENEActiv (GA) placed on the hip and the wrist and to
      develop regression equations for estimating energy expenditure. METHODS: Thirty
      children (7-11 yr) and 30 adults (18-65 yr) completed eight activities (ranging
      from lying to running) while wearing one AG and one GA on the hip and the wrist.
      Oxygen consumption (VO2) was measured with indirect calorimetry. Analysis
      involved the use of ANOVA to examine the effect of activity, brand, and placement
      on the acceleration values, intraclass correlation coefficient to evaluate the
      agreement between the two brands and placements, and linear regression to
      establish intensity thresholds. RESULTS: A significant difference in acceleration
      values between the hip and the wrist placement was found (P < 0.001). The output
      from the wrist placement was, in general, higher compared with that from the hip.
      There was no main effect of monitor brand in adults (P < 0.12) and children (P <
      0.73), and the intraclass correlation coefficient showed a strong agreement (0.96
      0.99). However, a three-way interaction and systematic error between the brands
      was found in children. Acceleration from both brands and placements showed a
      strong correlation with VO2. The intensity classification accuracy of the
      developed thresholds for both brands and placements was, in general, higher for
      adults compared with that for children and was greater for sedentary/light (93%
      97%), and vigorous activities (68%-92%) than that for moderate activities (33%
      59%). CONCLUSIONS: Accelerometer outputs from AG and GA seem comparable when
      attached to the same body location in adults, whereas inconsistent differences
      are apparent between the two brands and placements in children, hence limiting
      the comparability between brands in this age group.

PMID- 24887175
TI  - Acute responses of regional vascular conductance to oral ingestion of fructose in
      healthy young humans.
AB  - BACKGROUND: Recently, it was reported in healthy young subjects that fructose
      containing drinks increased blood pressure acutely, without any apparent change
      in total vascular conductance (TVC). However, because it is well known that the
      splanchnic vasculature is dilated by oral fructose ingestion, it is assumed to be
      the concomitant vasoconstriction in other peripheral region(s) that is
      responsible for this finding. Thus, the purpose of this study was to determine
      the acute response of regional VC to oral fructose ingestion in young healthy
      humans. RESULTS: In 12 healthy young subjects, mean arterial blood pressure
      (MAP), heart rate, cardiac output, and blood flow (BF) in the superior mesenteric
      (SMA), brachial (BA), and popliteal (PA) arteries, in addition to forearm skin
      BF, were measured continuously for 2 h after ingestion of 400 ml fructose
      solution (containing 50 g fructose). Regional VC was calculated as BF/MAP. MAP
      increased for 120 min after fructose ingestion without any change in TVC. While
      VC in the SMA was elevated after ingestion, VC in BA and PA and forearm skin
      decreased. CONCLUSIONS: While TVC was apparently unchanged during the 2 h after
      fructose ingestion, there were coincident changes in regional VCs in the
      peripheral circulation, but no net change in TVC.

PMID- 24887174
TI  - Generation of replication-proficient influenza virus NS1 point mutants with
      interferon-hyperinducer phenotype.
AB  - The NS1 protein of influenza A viruses is the dedicated viral interferon (IFN)
      antagonist. Viruses lacking NS1 protein expression cannot multiply in normal
      cells but are viable in cells deficient in their ability to produce or respond to
      IFN. Here we report an unbiased mutagenesis approach to identify positions in the
      influenza A NS1 protein that modulate the IFN response upon infection. A random
      library of virus ribonucleoproteins containing circa 40 000 point mutants in NS1
      were transferred to infectious virus and amplified in MDCK cells unable to
      respond to interferon. Viruses that activated the interferon (IFN) response were
      subsequently selected by their ability to induce expression of green-fluorescent
      protein (GFP) following infection of A549 cells bearing an IFN promoter-dependent
      GFP gene. Using this approach we isolated individual mutant viruses that
      replicate to high titers in IFN-compromised cells but, compared to wild type
      viruses, induced higher levels of IFN in IFN-competent cells and had a reduced
      capacity to counteract exogenous IFN. Most of these viruses contained not
      previously reported NS1 mutations within either the RNA-binding domain, the
      effector domain or the linker region between them. These results indicate that
      subtle alterations in NS1 can reduce its effectiveness as an IFN antagonist
      without affecting the intrinsic capacity of the virus to multiply. The general
      approach reported here may facilitate the generation of replication-proficient,
      IFN-inducing virus mutants, that potentially could be developed as attenuated
      vaccines against a variety of viruses. 

PMID- 24887176
TI  - Long non-coding RNAs in glioma: functional roles and clinical perspectives.
AB  - Long non-coding RNAs (lncRNAs) are a new class of non-coding gene regulators. But
      unlike their smaller counterparts, microRNAs, relatively less is known about the
      roles and functions of lncRNAs. Current evidence suggests that lncRNAs may play
      important roles in a wide range of biological processes in human cancers,
      including glioma. By acting as oncogenes or tumor suppressors, lncRNAs may
      contribute to glioma initiation, progression and other malignant phenotypes.
      Their expression profiles may also have important clinical implications in glioma
      subclassification and patients' prognostication. Here, we review current evidence
      related to the functional roles of lncRNAs in glioma. We will discuss the
      aberrant lncRNA expression signatures associated with glioma initiation and
      progression, as well as the potential mechanisms underlying lncRNA dysregulation.
      We also discuss the functional roles of lncRNAs in glioma biological behavior.
      Finally, the potentials and prospects of employing lncRNAs as novel biomarkers
      and therapeutic targets for glioma clinical practice will also be addressed. 

PMID- 24887177
TI  - Phylogenetic analysis of bovine viral diarrhea virus of subgenotype 1c.

PMID- 24887178
TI  - A rotation-translation invariant molecular descriptor of partial charges and its
      use in ligand-based virtual screening.
AB  - BACKGROUND: Measures of similarity for chemical molecules have been developed
      since the dawn of chemoinformatics. Molecular similarity has been measured by a
      variety of methods including molecular descriptor based similarity, common
      molecular fragments, graph matching and 3D methods such as shape matching.
      Similarity measures are widespread in practice and have proven to be useful in
      drug discovery. Because of our interest in electrostatics and high throughput
      ligand-based virtual screening, we sought to exploit the information contained in
      atomic coordinates and partial charges of a molecule. RESULTS: A new molecular
      descriptor based on partial charges is proposed. It uses the autocorrelation
      function and linear binning to encode all atoms of a molecule into two rotation
      translation invariant vectors. Combined with a scoring function, the descriptor
      allows to rank-order a database of compounds versus a query molecule. The
      proposed implementation is called ACPC (AutoCorrelation of Partial Charges) and
      released in open source. Extensive retrospective ligand-based virtual screening
      experiments were performed and other methods were compared with in order to
      validate the method and associated protocol. CONCLUSIONS: While it is a simple
      method, it performed remarkably well in experiments. At an average speed of 1649
      molecules per second, it reached an average median area under the curve of 0.81
      on 40 different targets; hence validating the proposed protocol and
      implementation.

PMID- 24887179
TI  - Is high-frequency oscillatory ventilation more effective and safer than
      conventional protective ventilation in adult acute respiratory distress syndrome
      patients? A meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: Comprehensively evaluating the efficacy and safety of high
      frequency oscillatory ventilation (HFOV) is important to allow clinicians who are
      using or considering this intervention to make appropriate decisions. METHODS: To
      find randomized controlled trials (RCTs) comparing HFOV with conventional
      mechanical ventilation (CMV) as an initial treatment for adult ARDS patients, we
      searched electronic databases (including PubMed, MedLine, Springer Link, Elsevier
      Science Direct, ISI web of knowledge, and EMBASE) with the following terms:
      "acute respiratory distress syndrome", "acute lung injury", and "high frequency
      oscillation ventilation". Additional sources included reference lists from the
      identified primary studies and relevant meta-analyses. Two investigators
      independently screened articles and extracted data. Meta-analysis was conducted
      using random-effects models. RESULTS: We included 6 RCTs with a total of 1,608
      patients in this meta-analysis. Compared with CMV, HFOV did not significantly
      reduce the mortality at 30 or 28 days. The pooled relative risk (RR) was 1.051
      (95% confidence interval (CI) 0.813 to 1.358). ICU mortality was also not
      significantly reduced in HFOV group, with a pooled RR of 1.218 (95% CI 0.925 to
      1.604). The pooled effect sizes of HFOV for oxygenation failure, ventilation
      failure and duration of mechanical ventilation were 0.557 (95% CI 0.351 to
      0.884), 0.892 (95% CI 0.435 to 1.829) and 0.079 (95% CI -0.045 to 0.203),
      respectively. The risk of barotrauma and hypotension were similar between the CMV
      group and HFOV group, with a RR of 1.205 (95% CI 0.834 to 1.742) and a RR of
      1.326 (95% CI 0.271 to 6.476), respectively. CONCLUSIONS: Although HFOV seems not
      to increase the risk of barotrauma or hypotension, and reduces the risk of
      oxygenation failure, it does not improve survival in adult acute respiratory
      distress syndrome patients.

PMID- 24887181
TI  - Functional pain: time for a new name.

PMID- 24887180
TI  - Trastuzumab emtansine: mechanisms of action and drug resistance.
AB  - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that is effective and
      generally well tolerated when administered as a single agent to treat advanced
      breast cancer. Efficacy has now been demonstrated in randomized trials as first
      line, second line, and later than the second line treatment of advanced breast
      cancer. T-DM1 is currently being evaluated as adjuvant treatment for early breast
      cancer. It has several mechanisms of action consisting of the anti-tumor effects
      of trastuzumab and those of DM1, a cytotoxic anti-microtubule agent released
      within thetarget cells upon degradation of the human epidermal growth factor
      receptor-2 (HER2)-T-DM1 complex in lysosomes. The cytotoxic effect of T-DM1
      likely varies depending on the intracellular concentration of DM1 accumulated in
      cancer cells, high intracellular levels resulting in rapid apoptosis, somewhat
      lower levels in impaired cellular trafficking and mitotic catastrophe, while the
      lowest levels lead to poor response to T-DM1. Primary resistance of HER2-positive
      metastatic breast cancer to T-DM1 appears to be relatively infrequent, but most
      patients treated with T-DM1 develop acquired drug resistance. The mechanisms of
      resistance are incompletely understood, but mechanisms limiting the binding of
      trastuzumab to cancer cells may be involved. The cytotoxic effect of T-DM1 may be
      impaired by inefficient internalization or enhanced recycling of the HER2-T-DM1
      complex in cancer cells, or impaired lysosomal degradation of trastuzumab or
      intracellular trafficking of HER2. The effect ofT-DM1 may also be compromised by
      multidrug resistance proteins that pump DM1 out of cancer cells. In this review
      we discuss the mechanism of action of T-DM1 and the key clinical results obtained
      with it, the combinations ofT-DM1 with other cytotoxic agents and anti-HER drugs,
      and the potential resistance mechanisms and the strategies to overcome resistance
      to T-DM1.

PMID- 24887183
TI  - In situ observation of step-edge in-plane growth of graphene in a STEM.
AB  - It is extremely difficult to control the growth orientation of the graphene layer
      in comparison to Si or III-V semiconductors. Here we report a direct observation
      of graphene growth and domain boundary formation in a scanning transmission
      electron microscope, with residual hydrocarbon in the microscope chamber being
      used as the carbon source for in-plane graphene growth at the step-edge of
      bilayer graphene substrate. We show that the orientation of the growth is
      strongly influenced by the step-edge structure and areas grown from a
      reconstructed 5-7 edge are rotated by 30 degrees  with respect to the mother
      layer. Furthermore, single heteroatoms like Si may act as catalytic active sites
      for the step-edge growth. The findings provide an insight into the mechanism of
      graphene growth and defect reconstruction that can be used to tailor carbon
      nanostructures with desired properties. 

PMID- 24887182
TI  - Stereoselective property of 20(S)-protopanaxadiol ocotillol type epimers affects
      its absorption and also the inhibition of P-glycoprotein.
AB  - Stereoselectivity has been proved to be tightly related to drug action including
      pharmacodynamics and pharmacokinetics. (20S,24R)-epoxy-dammarane-3,12,25-triol
      (24R-epimer) and (20S,24S)-epoxy-dammarane-3,12,25-triol (24S-epimer), a pair of
      20(S)-protopanaxadiol (PPD) ocotillol type epimers, were the main metabolites of
      PPD. Previous studies have shown that 24R-epimer and 24S-epimer had
      stereoselectivity in pharmacological action and pharmacokinetics. In the present
      study, the aim was to further study the pharmacokinetic characteristics of both
      epimers, investigate their absorption mechanism and analyze the selectivity
      effects of ocotillol type side chain and C24 stereo-configuration on P
      glycoprotein (P-gp) in vivo and in vitro. Results showed that the absolute
      bioavailability of 24R-epimer was about 14-fold higher than that of 24S-epimer,
      and a linear kinetic characteristic was acquired in doses of 5-20 mg/kg for both
      epimers after oral administration. Furthermore, the apparent permeability
      coefficients of 24R-epimer were 5-7 folds higher than that of 24S-epimer having
      lower efflux ratios in Caco-2 cell models. Moreover, both 24R-epimer and 24S
      epimer had similar inhibitory effects on P-gp by increasing cellular retention of
      rhodamine 123 in Caco-2 cells and decreasing efflux of digoxin across Caco-2 cell
      monolayers. In situ in vivo experiments showed that the inhibition of 24R-epimer
      on P-gp was stronger than that of 24S-epimer by single-pass intestinal perfusion
      of rhodamine 123 in rats. Western blot analyses demonstrated that both epimers
      had no action on P-gp expression in Caco-2 cells. In conclusion, with respect to
      the stereoselectivity, C24 S-configuration of the ocotillol type epimers
      processed a poor transmembrane permeability and could be distinguished by P-gp.
      Sharing a dammarane skeleton, both 24R-epimer and 24S-epimer were potent
      inhibitors of P-gp. This study provides a new case of stereoselective
      pharmacokinetics of chiral compounds which contributes to know the chiral
      characteristics of P-gp and structure-action relationship of PPD type and
      ocotillol type ginsenosides as a P-gp inhibitor. 

PMID- 24887184
TI  - Characterization of metastasis formation and virotherapy in the human C33A
      cervical cancer model.
AB  - More than 90% of cancer mortalities are due to cancer that has metastasized.
      Therefore, it is crucial to intensify research on metastasis formation and
      therapy. Here, we describe for the first time the metastasizing ability of the
      human cervical cancer cell line C33A in athymic nude mice after subcutaneous
      implantation of tumor cells. In this model, we demonstrated a steady progression
      of lumbar and renal lymph node metastases during tumor development. Besides
      predominantly occurring lymphatic metastases, we visualized the formation of
      hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A
      RFP cells. RFP positive cancer cells were found migrating in blood vessels and
      forming micrometastases in lungs of tumor-bearing mice. Next, we set out to
      analyze the influence of oncolytic virotherapy in the C33A-RFP model and
      demonstrated an efficient virus-mediated reduction of tumor size and metastatic
      burden. These results suggest the C33A-RFP cervical cancer model as a new
      platform to analyze cancer metastases as well as to test novel treatment options
      to combat metastases. 

PMID- 24887185
TI  - Effect of Linum usitatissimum L. (linseed) oil on mild and moderate carpal tunnel
      syndrome: a randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Carpal tunnel syndrome is known as the most common entrapment
      neuropathy. Conservative treatments cannot reduce the symptomatic severity
      satisfactorily; therefore, effectiveness of Linum usitatissimum L. (linseed) oil
      on carpal tunnel syndrome, as a complementary treatment, was evaluated in the
      current study. Linseed oil is a well-known preparation in Iranian traditional
      medicine and its analgesic, anti-inflammatory and anti-oxidative effects have
      been shown in previous studies. METHODS: A randomized, double-blind, placebo
      controlled clinical trial was conducted. One hundred patients (155 hands) with
      idiopathic mild to moderate carpal tunnel syndrome aged between 18 and 65 years
      old were randomized in two parallel groups. These two groups were treated during
      4 weeks with topical placebo and linseed oil. In addition, a night wrist splint
      was prescribed for both groups. Symptomatic severity and functional status were
      measured using Boston Carpal Tunnel Questionnaire. In addition, median sensory
      nerve conduction velocity, motor distal latency, sensory distal latency and
      compound latency as electrodiagnostic parameters were measured at baseline and
      after the intervention period. RESULTS: After the intervention, significant
      improvement was observed regarding Boston Carpal Tunnel Questionnaire symptomatic
      severity and functional status mean differences (p <0.001) in the linseed oil
      group compared with those in the placebo group. Also, regarding the mean
      differences of both groups, significant improvement of nerve conduction velocity
      of the median nerve was seen in the linseed oil group by a value of 2.38 m/sec (p
      < 0.05). However, motor distal latency and sensory distal latency of the median
      nerve showed no between-group significant changes (p = 0.14 for both items).
      Finally, compound latency was improved slightly in the case group, comparing mean
      differences between the groups (p <0.05). No significant adverse events were
      reported from using linseed oil. CONCLUSIONS: It seems that linseed oil could be
      effective in the management of mild and moderate carpal tunnel syndrome,
      especially in improving the severity of symptoms and functional status. In
      addition, its effect on electerodiagnostic parameters, especially on the nerve
      conduction velocity, can be considered as a valuable point.

PMID- 24887186
TI  - Quality improvement in pre-hospital critical care: increased value through
      research and publication.
AB  - Pre-hospital critical care is considered to be a complex intervention with a weak
      evidence base. In quality improvement literature, the value equation has been
      used to depict the inevitable relationship between resources expenditure and
      quality. Increased value of pre-hospital critical care involves moving a system
      from quality assurance to quality improvement. Agreed quality indicators can be
      integrated in existing quality improvement and complex intervention methodology.
      A QI system for pre-hospital critical care includes leadership involvement, multi
      disciplinary buy-in, data collection infrastructure and long-term commitment.
      Further, integrating process control with governance systems allows evidence
      based change of practice and publishing of results.

PMID- 24887187
TI  - The gluconeogenesis pathway is involved in maintenance of enterohaemorrhagic
      Escherichia coli O157:H7 in bovine intestinal content.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) are responsible for outbreaks of food-
      and water-borne illness. The bovine gastrointestinal tract (GIT) is thought to be
      the principle reservoir of EHEC. Knowledge of the nutrients essential for EHEC
      growth and survival in the bovine intestine may help in developing strategies to
      limit their shedding in bovine faeces thus reducing the risk of human illnesses.
      To identify specific metabolic pathways induced in the animal GIT, the
      transcriptome profiles of EHEC O157:H7 EDL933 during incubation in bovine small
      intestine contents (BSIC) and minimal medium supplemented with glucose were
      compared. The transcriptome analysis revealed that genes responsible for the
      assimilation of ethanolamine, urea, agmatine and amino acids (Asp, Thr, Gly, Ser
      and Trp) were strongly up-regulated suggesting that these compounds are the main
      nitrogen sources for EHEC in BSIC. A central role for the gluconeogenesis pathway
      and assimilation of gluconeogenic substrates was also pinpointed in EHEC
      incubated in BSIC. Our results suggested that three amino acids (Asp, Ser and
      Trp), glycerol, glycerol 3-phosphate, L-lactate and C4-dicarboxylates are
      important carbon sources for EHEC in BSIC. The ability to use gluconeogenic
      substrates as nitrogen sources (amino acids) and/or carbon sources (amino acids,
      glycerol and lactate) may provide a growth advantage to the bacteria in
      intestinal fluids. Accordingly, aspartate (2.4 mM), serine (1.9 mM), glycerol
      (5.8 mM) and lactate (3.6 mM) were present in BSIC and may represent the main
      gluconeogenic substrates potentially used by EHEC. A double mutant of E. coli
      EDL933 defective for phosphoenolpyruvate synthase (PpsA) and phosphoenolpyruvate
      carboxykinase (PckA), unable to utilize tricarboxylic acid (TCA) intermediates
      was constructed. Growth competition experiments between EHEC EDL933 and the
      isogenic mutant strain in BSIC clearly showed a significant competitive growth
      advantage of the wild-type strain further illustrating the importance of the
      gluconeogenesis pathway in maintaining EHEC in the bovine GIT. 

PMID- 24887188
TI  - Atopic dermatitis phenotypes in childhood.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease and can
      be the first step of the atopic march. OBJECTIVE: In this retrospective study, we
      analysed the immunological and clinical patterns of AD in a group of children
      affected by the disease since their first years of life, in order to evaluate if
      and how these patterns can change over time, and to identify biomarkers that can
      possibly correlate with the clinical phenotype. METHODS: We enrolled Caucasian
      children with diagnosis of AD performed by a specialist on the basis of Hanifin
      and Rajka's criteria and with a first clinical and laboratory evaluation before 5
      years of age. Patients were divided in 2 groups: IgE-associated AD (with or
      without allergic respiratory diseases) and non-IgE-associated AD. RESULTS: Among
      184 patients enrolled in this study, at the beginning 30/184 were classified as
      having non-IgE-associated AD, but during follow-up, at the median age of 36
      months, 15 patients became allergic. All 15 patients who switched from the non
      IgE to the IgE-associated form had a significantly earlier onset of AD than those
      who did not switch. Dust mite sensitization seem to be the best biomarker (OR
      2.86) to predict the appearance of allergic respiratory diseases. CONCLUSION: IgE
      associated AD is more frequent in childhood than non-IgE-associated AD. These two
      phenotypes are different in the age of onset and in the remission patterns. In
      the first years of life, it is important to distinguish the different phenotypes
      in order to evaluate possible allergic related conditions.

PMID- 24887189
TI  - The effect of organohalogen contaminants on western Steller sea lion survival and
      movement in the Russian Far East.
AB  - The western stock of Steller sea lions (Eumetopias jubatus) have experienced
      dramatic declines since the 1960s, particularly in the western Alaskan and Asian
      portions, which have continued to decline or stabilized at low levels. Multiple
      causes for this decline have been proposed and may include anthropogenic
      contamination from organohalogen contaminants (OCs). These include
      polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), which
      have not been ruled out as a potential cause for the lack of recovery. The
      objective of this study was to determine the effects of OCs on survival and
      movement probabilities estimated in program MARK using resighting data collected
      from 2003 to 2009. PCBs and DDTs were measured in whole blood from 136 (74 males
      and 62 females) individually marked, free-ranging pups from four Russian Far East
      rookeries. The mean concentration of ?PCB and ?DDT was 4.25+/-5.12 and 3.22+/
      4.28 ng g(-1) ww (n=136), respectively, and the average ?PCB and ?DDT
      concentration for those above the aggregate mean (n=44) was 9.25+/-6.55 and
      7.65+/-5.21 ng g(-1) ww, and those below the aggregate mean (n=92) the
      concentration was 1.86+/-0.89 and 1.11+/-0.65 ng g(-1) ww, respectively. The
      lowest estimated probabilities of survival occurred in the first year, ranging
      from 38% to 74%, but increased for ages 1-9, ranging from 82% to 94%. The
      greatest movement occurred from Medny Island west toward the Kamchatka Peninsula
      (33%) and to Bering Island (18%), and low movement estimates for other natal
      rookeries was largely due to minimal resighting effort. The estimated
      probabilities of resighting varied by location (48%-87%), but had greater
      precision than survival or movement parameters. Survival and movement were most
      affected by age and location rather than OCs.

PMID- 24887190
TI  - Fate and transport of monensin in the presence of nonionic surfactant Brij35 in
      soil.
AB  - As fresh water is a limited resource in many parts of the world, the use of
      wastewater for irrigation has become an important alternative. Therefore, many
      countries facing a water deficit, use partially treated, or even untreated,
      wastewater. This may increase the input of many contaminants into the
      environment. In the present study, we investigated the effect of using surfactant
      rich water in irrigation on the mobility of the most commonly-used veterinary
      antibiotic, monensin. Nine PVC lysimeters, 1.0m long*0.45 m diameter, were packed
      with a sandy soil to a bulk density of 1.35 Mg m(-3). Cattle manure, containing
      monensin, was applied at the surface of the lysimeters at the recommended rate of
      10t/ha. Each of three aqueous Brij 35 solutions, 0, 0.5 and 5 g L(-1), was
      applied to the lysimeters in triplicate. Over a 90 day period, soil and leachate
      samples were collected and analyzed. The results of the laboratory sorption
      experiment showed that when the nonionic surfactant Brij 35 is present, the
      sorption coefficient of monensin was reduced significantly from 120.22 mL g(-1)
      in the aqueous medium to 112.20, 100 and 63.09 mL g(-1) with Brij35
      concentrations of 0.25, 2.5 and 5 g L(-1), respectively. The lysimeter results
      indicated a significant downward movement of monensin at depths of 60 cm in the
      soil profile and leachate in the presence of the surfactant. Thus, the continuous
      use of poor quality water could influence the transport of monensin in
      agricultural soils, and consequently, pose a risk for groundwater pollution.

PMID- 24887191
TI  - Mechanistic and kinetic studies on the OH-initiated atmospheric oxidation of
      fluoranthene.
AB  - The atmospheric oxidation of polycyclic aromatic hydrocarbons (PAHs) can generate
      toxic derivatives which contribute to the carcinogenic potential of particulate
      organic matter. In this work, the mechanism of the OH-initiated atmospheric
      oxidation of fluoranthene (Flu) was investigated by using high-accuracy molecular
      orbital calculations. All of the possible oxidation pathways were discussed, and
      the theoretical results were compared with the available experimental
      observation. The rate constants of the crucial elementary reactions were
      evaluated by the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The main oxidation
      products are a range of ring-retaining and ring-opening chemicals containing
      fluoranthols, fluoranthones, fluoranthenequinones, nitro-fluoranthenes,
      dialdehydes and epoxides. The overall rate constant of the OH addition reaction
      is 1.72*10(-11) cm(3) molecule(-1) s(-1) at 298 K and 1 atm. The atmospheric
      lifetime of Flu determined by OH radicals is about 0.69 days. This work provides
      a comprehensive investigation of the OH-initiated oxidation of Flu and should
      help to clarify its atmospheric conversion.

PMID- 24887192
TI  - The influence of governmental mitigation measures on contamination
      characteristics of PM(2.5) in Beijing.
AB  - Beijing, the capital of China, has become one of the most air-polluted cities due
      to its rapid economic growth. Weekly PM2.5 samples-collected continuously from
      2007 to 2010-were used to study the contamination characteristics of atmospheric
      particles and effects of governmental mitigation measures especially since the
      2008 Summer Olympic Games. PM2.5 mass concentrations during the sampling period
      were reduced compared to the previous studies before 2005, although they were
      still too high in comparison with environmental standards of China and many other
      countries as well as WHO standards. Results of principle component analysis show
      that elements of primary anthropogenic origin had an obvious decline while
      elements mainly from the natural environment kept a relatively stable course. The
      governmental macro-control measures influenced both anthropogenic and geogenic
      sources, but they also led to some pollution peaks prior to implementation of the
      respective measures. Some element concentrations correlated to the
      restrictiveness of relative measures, especially during different traffic
      restrictions. The comparison with other countries and international standards
      shows that there is a long way to go in order to improve air quality in Beijing,
      and that governmental mitigation measures need to be continued and reinforced. 

PMID- 24887193
TI  - Recent history of sediment metal contamination in Lake Macquarie, Australia, and
      an assessment of ash handling procedure effectiveness in mitigating metal
      contamination from coal-fired power stations.
AB  - This study assessed historical changes in metal concentrations in sediments of
      southern Lake Macquarie resulting from the activities of coal-fired power
      stations, using a multi-proxy approach which combines (210)Pb, (137)Cs and metal
      concentrations in sediment cores. Metal concentrations in the lake were on
      average, Zn: 67 mg/kg, Cu: 15 mg/kg, As: 8 mg/kg, Se: 2mg/kg, Cd: 1.5 mg/kg, Pb:
      8 mg/kg with a maximum of Zn: 280 mg/kg, Cu: 80 mg/kg, As: 21 mg/kg, Se: 5 mg/kg,
      Cd: 4 mg/kg, Pb: 48 mg/kg. The ratios of measured concentrations in sediment
      cores to their sediment guidelines were Cd 1.8, As 1.0, Cu 0.5, Pb 0.2 and Zn
      0.2, with the highest concern being for cadmium. Of special interest was
      assessment of the effects of changes in ash handling procedures by the Vales
      Point power station on the metal concentrations in the sediments. Comparing
      sediment layers before and after ash handling procedures were implemented, zinc
      concentrations have decreased 10%, arsenic 37%, selenium 20%, cadmium 38% and
      lead 14%. An analysis of contaminant depth profiles showed that, after
      implementation of new ash handling procedures in 1995, selenium and cadmium, the
      main contaminants in Australian black coal had decreased significantly in this
      estuary.

PMID- 24887194
TI  - Partitioning of alcohol ethoxylates and polyethylene glycols in the marine
      environment: field samplings vs laboratory experiments.
AB  - Nowadays, alcohol ethoxylates (AEOs) constitute the most important group of non
      ionic surfactants, used in a wide range of applications such as household
      cleaners and detergents. Significant amounts of these compounds and their
      degradation products (polyethylene glycols, PEGs, which are also used for many
      other applications) reach aquatic environments, and are eliminated from the water
      column by degradation and sorption processes. This work deals with the
      environmental distribution of AEOs and PEGs in the Long Island Sound Estuary, a
      setting impacted by sewage discharges from New York City (NYC). The distribution
      of target compounds in seawater was influenced by tides, consistent with salinity
      differences, and concentrations in suspended solid samples ranged from 1.5 to
      20.5 MUg/g. The more hydrophobic AEOs were mostly attached to the particulate
      matter whereas the more polar PEGs were predominant in the dissolved form. Later,
      the sorption of these chemicals was characterized in the laboratory. Experimental
      and environmental sorption coefficients for AEOs and PEGs showed average values
      from 3607 to 164,994 L/kg and from 74 to 32,862 L/kg, respectively. The sorption
      data were fitted to a Freundlich isotherm model with parameters n and log KF
      between 0.8-1.2 and 1.46-4.39 L/kg, respectively. AEO and PEG sorptions on marine
      sediment were also found to be mostly not affected by changes in salinity.

PMID- 24887195
TI  - Agents of earthy-musty taste and odor in water: evaluation of cytotoxicity,
      genotoxicity and toxicogenomics.
AB  - Considering the limited number of studies on the biological effects on human
      health of cyanobacterial compounds that cause taste and odor, the present study
      assessed the cytotoxic and genotoxic potentials of 2-methylisoborneol (2-MIB) and
      geosmin (GEO) using the MTT assay and the in vitro comet and cytokinesis-block
      micronucleus (CBMN-Cyt) assays in human HepG2 cells. The toxicogenomics of genes
      responsive to DNA damage and metabolization by the exposure of cells to 2-MIB and
      GEO were also investigated. The results showed that concentrations of 2-MIB and
      GEO above 100 and 75 MUg/mL, respectively, were cytotoxic to HepG2 cells. Doses
      of 2-MIB (12.5, 25, 50, 75 and 100 MUg/mL) and GEO (12.5, 25, 50, and 75 MUg/mL)
      were unable to induce neither DNA damage nor events associated with chromosomal
      instability. Similarly, no concentration of each compound induced increments in
      the expression of CDKN1A, GADD45alpha, MDM2 and TP53 DNA damage responsive genes
      as well as in CYP1A1 and CYP1A2 metabolizing genes. Although cytotoxicity was
      observed, concentrations that caused it are much higher than those expected to
      occur in aquatic environments. Thus, environmentally relevant concentrations of
      both compounds are not expected to exhibit cytotoxicity or genotoxicity to
      humans.

PMID- 24887197
TI  - Social change and birth cohort increase in loneliness among Chinese older adults:
      a cross-temporal meta-analysis, 1995-2011.
AB  - BACKGROUND: In China, rapid economic growth and increasing social problems
      constitute the two basic characteristics underlying contemporary social change.
      With dramatic social change, loneliness in older adults may have changed across
      birth cohorts, thus altering older adults' mental health. The present study aims
      to identify birth cohort changes in Chinese older adults' loneliness and the
      social indicators underlying these changes. METHODS: Cross-temporal meta-analysis
      was utilized to investigate changes in Chinese older adults' loneliness from 1995
      to 2011. We analyzed 25 studies (N = 13,280 adults; age >= 60 years) employing
      the University of California at Los Angeles Loneliness Scale. We correlated
      loneliness scores with social indicators and matched these correlations for three
      periods: ten years before the data collection, five years before data collection,
      and during the year of data collection. RESULTS: Loneliness levels in Chinese
      older adults have increased by 1.02 standard deviations from 1995 to 2011. Social
      indicators such as increased urbanization level, personal medical expenditure,
      divorce rate, the Gini coefficient, and unemployment rate significantly predicted
      loneliness in Chinese older adults. Decrease in social connectedness and increase
      in levels of health threat may be responsible for the observed increase in levels
      of loneliness. CONCLUSIONS: Cross-temporal meta-analysis revealed a birth cohort
      increase in loneliness among Chinese older adults. We conclude that changes in
      social connectedness and levels of health threat likely play an important role in
      predicting loneliness in the population of Chinese elderly adults.

PMID- 24887198
TI  - Erythrocyte selenium concentration predicts intensive care unit and hospital
      mortality in patients with septic shock: a prospective observational study.
AB  - INTRODUCTION: Selenoenzymes can modulate the extent of oxidative stress, which is
      recognized as a key feature of septic shock. The pathophysiologic role of
      erythrocyte selenium concentration in patients with septic shock remains unknown.
      Therefore, the objective of this study was to evaluate the association of
      erythrocyte selenium concentration with glutathione peroxidase (GPx1) activity,
      GPx1 polymorphisms and with ICU and hospital mortality in septic shock patients.
      METHODS: This prospective study included all patients older than 18 years with
      septic shock on admission or during their ICU stay, admitted to one of the three
      ICUs of our institution, from January to August 2012. At the time of the
      patients' enrollment, demographic information was recorded. Blood samples were
      taken within the first 72 hours of the patients' admission or within 72 hours of
      the septic shock diagnosis for determination of selenium status, protein carbonyl
      concentration, GPx1 activity and GPx1 Pro198Leu polymorphism (rs 1050450)
      genotyping. RESULTS: A total of 110 consecutive patients were evaluated. The mean
      age was 57.6 +/- 15.9 years, 63.6% were male. Regarding selenium status, only
      erythrocyte selenium concentration was lower in patients who died in the ICU. The
      frequencies for GPx1 Pro198Leu polymorphism were 55%, 38% and 7% for Pro/Pro,
      Pro/Leu and Leu/Leu, respectively. In the logistic regression models, erythrocyte
      selenium concentration was associated with ICU and hospital mortality in patients
      with septic shock even after adjustment for protein carbonyl concentration and
      acute physiology and chronic health evaluation II score (APACHE II) or sequential
      organ failure assessment (SOFA). CONCLUSIONS: Erythrocyte selenium concentration
      was a predictor of ICU and hospital mortality in patients with septic shock.
      However, this effect was not due to GPx1 activity or Pro198Leu polymorphism.

PMID- 24887200
TI  - The direction of evolution: the rise of cooperative organization.
AB  - Two great trends are evident in the evolution of life on Earth: towards
      increasing diversification and towards increasing integration. Diversification
      has spread living processes across the planet, progressively increasing the range
      of environments and free energy sources exploited by life. Integration has
      proceeded through a stepwise process in which living entities at one level are
      integrated into cooperative groups that become larger-scale entities at the next
      level, and so on, producing cooperative organizations of increasing scale (for
      example, cooperative groups of simple cells gave rise to the more complex
      eukaryote cells, groups of these gave rise to multi-cellular organisms, and
      cooperative groups of these organisms produced animal societies). The trend
      towards increasing integration has continued during human evolution with the
      progressive increase in the scale of human groups and societies. The trends
      towards increasing diversification and integration are both driven by selection.
      An understanding of the trajectory and causal drivers of the trends suggests that
      they are likely to culminate in the emergence of a global entity. This entity
      would emerge from the integration of the living processes, matter, energy and
      technology of the planet into a global cooperative organization. Such an
      integration of the results of previous diversifications would enable the global
      entity to exploit the widest possible range of resources across the varied
      circumstances of the planet. This paper demonstrates that it's case for
      directionality meets the tests and criticisms that have proven fatal to previous
      claims for directionality in evolution. 

PMID- 24887199
TI  - Comparative genomic characterization of a Thailand-Myanmar isolate, MS6, of
      Vibrio cholerae O1 El Tor, which is phylogenetically related to a "US Gulf Coast"
      clone.
AB  - BACKGROUND: The cholera outbreaks in Thailand during 2007-2010 were exclusively
      caused by the Vibrio cholerae O1 El Tor variant carrying the cholera toxin gene
      of the classical biotype. We previously isolated a V. cholerae O1 El Tor strain
      from a patient with diarrhea and designated it MS6. Multilocus sequence-typing
      analysis revealed that MS6 is most closely related to the U. S. Gulf Coast clone
      with the exception of two novel housekeeping genes. METHODOLOGY/PRINCIPAL
      FINDINGS: The nucleotide sequence of the genome of MS6 was determined and
      compared with those of 26 V. cholerae strains isolated from clinical and
      environmental sources worldwide. We show here that the MS6 isolate is distantly
      related to the ongoing seventh pandemic V. cholerae O1 El Tor strains. These
      strains differ with respect to polymorphisms in housekeeping genes, seventh
      pandemic group-specific markers, CTX phages, two genes encoding predicted
      transmembrane proteins, the presence of metY (MS6_A0927) or hchA/luxR in a highly
      conserved region of the V. cholerae O1 serogroup, and a superintegron (SI). We
      found that V. cholerae species carry either hchA/luxR or metY and that the V.
      cholerae O1 clade commonly possesses hchA/luxR, except for MS6 and U. S. Gulf
      Coast strains. These findings illuminate the evolutionary relationships among V.
      cholerae O1 strains. Moreover, the MS6 SI carries a quinolone-resistance gene
      cassette, which was closely related with those present in plasmid-borne integrons
      of other gram-negative bacteria. CONCLUSIONS/SIGNIFICANCE: Phylogenetic analysis
      reveals that MS6 is most closely related to a U. S. Gulf Coast clone, indicating
      their divergence before that of the El Tor biotype strains from a common V.
      cholerae O1 ancestor. We propose that MS6 serves as an environmental aquatic
      reservoir of V. cholerae O1.

PMID- 24887201
TI  - Synthesis and evaluation of nitroxide-based oligoradicals for low-temperature
      dynamic nuclear polarization in solid state NMR.
AB  - We describe the synthesis of new nitroxide-based biradical, triradical, and
      tetraradical compounds and the evaluation of their performance as paramagnetic
      dopants in dynamic nuclear polarization (DNP) experiments in solid state nuclear
      magnetic resonance (NMR) spectroscopy with magic-angle spinning (MAS). Under our
      experimental conditions, which include temperatures in the 25-30 K range, a 9.4 T
      magnetic field, MAS frequencies of 6.2-6.8 kHz, and microwave irradiation at
      264.0 GHz from a 800 mW extended interaction oscillator source, the most
      effective compounds are triradicals that are related to the previously-described
      compound DOTOPA-TEMPO (see Thurber et al., 2010), but have improved solubility in
      glycerol/water solvent near neutral pH. Using these compounds at 30 mM total
      nitroxide concentration, we observe DNP enhancement factors of 92-128 for cross
      polarized (13)C NMR signals from (15)N,(13)C-labeled melittin in partially
      protonated glycerol/water, and build-up times of 2.6-3.8s for (1)H spin
      polarizations. Net sensitivity enhancements with biradical and tetraradical
      dopants, taking into account absolute (13)C NMR signal amplitudes and build-up
      times, are approximately 2-4 times lower than with the best triradicals.

PMID- 24887202
TI  - Interpreting human genetic variation with in vivo zebrafish assays.
AB  - Rapid advances and cost erosion in exome and genome analysis of patients with
      both rare and common genetic disorders have accelerated gene discovery and
      illuminated fundamental biological mechanisms. The thrill of discovery has been
      accompanied, however, with the sobering appreciation that human genomes are
      burdened with a large number of rare and ultra rare variants, thereby posing a
      significant challenge in dissecting both the effect of such alleles on protein
      function and also the biological relevance of these events to patient pathology.
      In an effort to develop model systems that are able to generate surrogates of
      human pathologies, a powerful suite of tools have been developed in zebrafish,
      taking advantage of the relatively small (compared to invertebrate models)
      evolutionary distance of that genome to humans, the orthology of several organs
      and signaling processes, and the suitability of this organism for medium and high
      throughput phenotypic screening. Here we will review the use of this model
      organism in dissecting human genetic disorders; we will highlight how diverse
      strategies have informed disease causality and genetic architecture; and we will
      discuss relative strengths and limitations of these approaches in the context of
      medical genome sequencing. This article is part of a Special Issue entitled: From
      Genome to Function.

PMID- 24887204
TI  - Photoresponsive liquid crystals based on halogen bonding of azopyridines.
AB  - A series of photoresponsive halogen-bonded liquid crystals (LCs) were
      successfully constructed using molecular halogen and azopyridine compounds, which
      show interesting properties of photoinduced phase transition upon UV irradiation.
      In addition, bromine-bonded LCs were first obtained with high mesophase
      stability. 

PMID- 24887203
TI  - Early alterations in energy metabolism in the hippocampus of APPswe/PS1dE9 mouse
      model of Alzheimer's disease.
AB  - The present study had focused on the behavioral phenotype and gene expression
      profile of molecules related to insulin receptor signaling in the hippocampus of
      3 and 6 month-old APPswe/PS1dE9 (APP/PS1) transgenic mouse model of Alzheimer's
      disease (AD). Elevated levels of the insoluble Abeta (1-42) were detected in the
      brain extracts of the transgenic animals as early as 3 months of age, prior to
      the Abeta plaque formation (pre-plaque stage). By the early plaque stage (6
      months) both the soluble and insoluble Abeta (1-40) and Abeta (1-42) peptides
      were detectable. We studied the expression of genes related to memory function
      (Arc, Fos), insulin signaling, including insulin receptor (Insr), Irs1 and Irs2,
      as well as genes involved in insulin growth factor pathways, such as Igf1, Igf2,
      Igfr and Igfbp2. We also examined the expression and protein levels of key
      molecules related to energy metabolism (PGC1-alpha, and AMPK) and mitochondrial
      functionality (OXPHOS, TFAM, NRF1 and NRF2). 6 month-old APP/PS1 mice
      demonstrated impaired cognitive ability, were glucose intolerant and showed a
      significant reduction in hippocampal Insr and Irs2 transcripts. Further
      observations also suggest alterations in key cellular energy sensors that
      regulate the activities of a number of metabolic enzymes through phosphorylation,
      such as a decrease in the Prkaa2 mRNA levels and in the pAMPK (Thr172)/Total APMK
      ratio. Moreover, mRNA and protein analysis reveals a significant downregulation
      of genes essential for mitochondrial replication and respiratory function,
      including PGC-1alpha in hippocampal extracts of APP/PS1 mice, compared to age
      matched wild-type controls at 3 and 6 months of age. Overall, the findings of
      this study show early alterations in genes involved in insulin and energy
      metabolism pathways in an APP/PS1 model of AD. These changes affect the activity
      of key molecules like NRF1 and PGC-1alpha, which are involved in mitochondrial
      biogenesis. Our results reinforce the hypothesis that the impairments in both
      insulin signaling and energy metabolism precede the development of AD
      amyloidogenesis.

PMID- 24887205
TI  - Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway
      of apoptosis in human leukemia (HL-60) cells.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid
      leukemia (AML), which accounts for approximately 10% of all acute myloid leukemia
      cases. It is a blood cancer that is formed by chromosomal mutation. Each year in
      the United States, APL affects about 1,500 patients of all age groups and causes
      approximately 1.2% of cancer deaths. Arsenic trioxide (ATO) has been used
      successfully for treatment of APL patients, and both induction and consolidated
      therapy have resulted in complete remission. Recently published studies from our
      laboratory have demonstrated that ATO pharmacology as an anti-leukemic drug is
      associated with cytotoxic and genotoxic effects in leukemia cells. METHODS: In
      the present study, we further investigated the detailed molecular mechanism of
      ATO-mediated intrinsic pathway of apoptosis; using HL-60 cells as a test model.
      Oxidative stress was assessed by spectrophotometric measurements of MDA and GSH
      levels while genotoxicity was determined by single cell gel electrophoresis
      (Comet assay). Apoptosis pathway was analyzed by Western blot analysis of Bax,
      Bcl2 and caspase 3 expression, as well as immunocytochemistry and confocal
      imaging of Bax and Cyt c translocation and mitochondrial membrane potential
      depolarization. RESULTS: ATO significantly (p < 0.05) induces oxidative stress,
      DNA damage, and caspase 3 activity in HL-60 cells in a dose-dependent manner. It
      also activated the intrinsic pathway of apoptosis by significantly modulating (p
      < 0.05) the expression and translocation of apoptotic molecules and decreasing
      the mitochondrial membrane potential in leukemia cells. CONCLUSION: Taken
      together, our research demonstrated that ATO induces mitochondrial pathway of
      apoptosis in HL-60 cells. This apoptotic signaling is modulated via oxidative
      stress, DNA damage, and change in mitochondrial membrane potential, translocation
      and upregulation of apoptotic proteins leading programmed cell death.

PMID- 24887206
TI  - Non-enhanced T1-weighted liver vessel imaging at 7 Tesla.
AB  - OBJECTIVES: Aim of the study was to assess the feasibility and to compare three
      non-enhanced T1-weighted (w) sequences for liver vessel imaging at 7 Tesla (T).
      MATERIAL AND METHODS: 12 healthy volunteers were examined on a 7 T whole-body MR
      system. The following non-enhanced sequences were acquired: T1w 2D FLASH, T1w 3D
      FLASH and Time of flight (TOF)-MRA. Qualitative image analysis was performed by
      two radiologists including over all image quality as well as vessel delineation
      of the liver arteries, liver veins and portal vein and the presence of artifacts
      using a five-point scale (5 = excellent vessel delineation to 1 = non
      diagnostic). Contrast ratios (CR), SNR und CNR of the above named vessels in
      correlation to adjacent liver tissue were calculated for quantitative assessment.
      For statistical analysis, a Wilcoxon Rank Test was applied. RESULTS: All three
      sequences provided a homogenous hyperintense delineation of the assessed liver
      vessels. Qualitative image analysis demonstrated the superiority of TOF-MRA,
      providing best overall image quality (TOF 4.17, 2D FLASH 3.42, 3D FLASH 3.46;
      p<0.01) as well as highest image quality values for all analyzed liver vessel
      segments. TOF-MRA was least impaired by B1 inhomogeneity (4.13) and
      susceptibility artifacts (4.63) out of all three sequences (p<0.01). Quantitative
      image analysis confirmed the superiority of TOF MRA showing significant higher CR
      values for all liver vessels (e.g. right hepatic artery TOF 0.47, 2D FLASH 0.09,
      3D FLASH 0.11 with p = 0.02 and 0.01, respectively). Providing the lowest
      standard deviation in noise, TOF showed highest values for SNR and CNR.
      CONCLUSIONS: Non-enhanced T1w imaging in general and TOF MRA in particular,
      appear to be promising techniques for high quality non-enhanced liver vessel
      assessment at 7 T.

PMID- 24887207
TI  - Conformational specificity of the C4F6 SOD1 antibody; low frequency of reactivity
      in sporadic ALS cases.
AB  - Greater than 160 missense mutations in copper-zinc superoxide dismutase-1 (SOD1)
      can cause amyotrophic lateral sclerosis (ALS). These mutations produce
      conformational changes that reveal novel antibody binding epitopes. A monoclonal
      antibody, clone C4F6 - raised against the ALS variant G93A of SOD1, has been
      identified as specifically recognizing a conformation shared by many ALS mutants
      of SOD1. Attempts to determine whether non-mutant SOD1 adopts a C4F6-reactive
      conformation in spinal tissues of sporadic ALS (sALS) patients has produced
      inconsistent results. To define the epitope recognized by C4F6, we tested its
      binding to a panel of recombinant ALS-SOD1 proteins expressed in cultured cells,
      producing data to suggest that the C4F6 epitope minimally contains amino acids 90
      93, which are normally folded into a tight hairpin loop. Multiple van der Waals
      interactions between the 90-93 loop and a loop formed by amino acids 37-42,
      particularly a leucine at position 38, form a stable structure termed the beta
      plug. Based on published modeling predictions, we suggest that the binding of
      C4F6 to multiple ALS mutants of SOD1 occurs when the local structure within the
      beta-plug, including the loop at 90-93, is destabilized. In using the antibody to
      stain tissues from transgenic mice or humans, the specificity of the antibody for
      ALS mutant SOD1 was influenced by antigen retrieval protocols. Using conditions
      that showed the best discrimination between normal and misfolded mutant SOD1 in
      cell and mouse models, we could find no obvious difference in C4F6 reactivity to
      spinal motor neurons between sALS and controls tissues.

PMID- 24887208
TI  - Micro-costing studies in the health and medical literature: protocol for a
      systematic review.
AB  - BACKGROUND: Micro-costing is a cost estimation method that allows for precise
      assessment of the economic costs of health interventions. It has been
      demonstrated to be particularly useful for estimating the costs of new
      interventions, for interventions with large variability across providers, and for
      estimating the true costs to the health system and to society. However, existing
      guidelines for economic evaluations do not provide sufficient detail of the
      methods and techniques to use when conducting micro-costing analyses. Therefore,
      the purpose of this study is to review the current literature on micro-costing
      studies of health and medical interventions, strategies, and programs to assess
      the variation in micro-costing methodology and the quality of existing studies.
      This will inform current practice in conducting and reporting micro-costing
      studies and lead to greater standardization in methodology in the future.
      METHODS/DESIGN: We will perform a systematic review of the current literature on
      micro-costing studies of health and medical interventions, strategies, and
      programs. Using rigorously designed search strategies, we will search Ovid
      MEDLINE, EconLit, BIOSIS Previews, Embase, Scopus, and the National Health
      Service Economic Evaluation Database (NHS EED) to identify relevant English
      language articles. These searches will be supplemented by a review of the
      references of relevant articles identified. Two members of the review team will
      independently extract detailed information on the design and characteristics of
      each included article using a standardized data collection form. A third reviewer
      will be consulted to resolve discrepancies. We will use checklists that have been
      developed for critical appraisal of health economics studies to evaluate the
      quality and potential risk of bias of included studies. DISCUSSION: This
      systematic review will provide useful information to help standardize the methods
      and techniques for conducting and reporting micro-costing studies in research,
      which can improve the quality and transparency of future studies and enhance
      comparability and interpretation of findings. In the long run, these efforts will
      facilitate clinical and health policy decision-making about resource allocation.
      TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42014007453.

PMID- 24887210
TI  - Neuroprotective-neurotrophic effect of endogenous dehydroepiandrosterone sulfate
      during intense stress exposure.
AB  - Recent reports demonstrate neurotrophic properties of dehydroepiandrosterone
      sulfate (DHEAS) in men at rest, as well as profound neurotrophic responses to
      stress in both men and women. Little is known of neuroprotective-neurotrophic
      effects of DHEAS during stress exposure, either in men or women. This
      translational study was designed to examine neuroprotective-neurotrophic effects
      of DHEAS throughout intense stress exposure in healthy men and women. The study
      took place within a stressful 12-day military survival course. Utilizing a
      longitudinal cross-sectional repeated measures design, One hundred sixteen
      healthy active-duty military personnel (80% male) were studied before, during,
      and 24h after the course. The dependent variable was the neurotrophin salivary
      nerve growth factor (sNGF). In terms of total hormone output, the effect of DHEAS
      on sNGF was mediated by testosterone. Unlike testosterone or cortisol, DHEAS
      reliably predicted sNGF at each time point, and change in DHEAS predicted change
      in sNGF across time points. Baseline DHEAS predicted total sNGF output across the
      stress trajectory. Consistent with preclinical as well as cross-sectional human
      research, this study demonstrates neuroprotective-neurotrophic effects of DHEAS
      in healthy men and women exposed to intense stress. Results are evaluated in
      relation to established criteria for causation. 

PMID- 24887209
TI  - Contact lens care solutions: a pilot study of ethnic differences in clinical
      signs and symptoms.
AB  - OBJECTIVES: To determine whether Asian and white subjects differ in clinical
      signs or subjective symptoms in response to the use of different biguanide
      preserved contact lens care solutions. METHODS: Forty-two subjects (15 Asian and
      27 white) wearing lotrafilcon B silicone hydrogel contact lenses used a
      preservative-free lens care solution bilaterally for 2 weeks, then used two
      biguanide-preserved solutions (solution 1: ReNu MPS; solution 2: AQuify MPS)
      contralaterally in randomly assigned eyes for 4 weeks. Comprehensive ocular
      surface examinations were performed and symptomatology questionnaires were
      administered every 2 weeks. Investigators were masked as to solution assignment
      during examinations, whereas subjects were not to avoid potential difficulties in
      compliance with the protocol. RESULTS: With solution 1, most Asian and white
      subjects had grade 2 or greater corneal staining after 2 weeks (67% and 59%,
      respectively) and 4 weeks (60% and 67%, respectively). With solution 2, grade 2
      or greater corneal staining occurred in 40% of Asians after 2 weeks and in 13%
      after 4 weeks, but in only 4% of whites after 2 weeks and 0% after 4 weeks.
      Whites reported significantly better average comfort (P=0.046) and less dryness
      (P<0.001) than did Asians. CONCLUSIONS: Asians and whites differ in both ocular
      response to the use of contact lens care solutions and in reporting subjective
      symptoms. Racial and ethnic differences should be considered when evaluating and
      treating contact lens patients in a clinical setting.

PMID- 24887211
TI  - Biological age and tempos of aging in women over 60 in connection with their
      morphofunctional characteristics.
AB  - BACKGROUND: The study of aging processes and the changes in morphological,
      physiological, and functional characteristics that are associated with aging is
      of great interest not only for researchers, but also for the general public. The
      aim of the present paper is to study the biological age and tempos of aging in
      women older than 60 years, including long-lived females (over 90-years-old), and
      their associations with morphofunctional characteristics. RESULTS: Somatic
      traits, body mass components, and functional characteristics were investigated in
      119 elderly (between 60 and 74-years-old) and long-lived (over 90-years-old)
      women in Tiraspol. With the special PC software 'Diagnostics of Aging: BioAge'
      (National Gerontological Center, Moscow, Russia) the biological age and tempos of
      aging were evaluated in the study participants. The results show close
      connections between morphofunctional changes, particularly in body mass
      components, and biological age. The software demonstrated its validity in the
      estimation of biological age in the group of elderly women. In the homogenous
      (according to their chronological age) group of women, three subgroups were
      separated with different tempos of aging: those with lower rates of aging
      (biological age less than chronological age by two years or more); those
      consistent with their chronological age, and those with accelerated tempos of
      aging (biological age higher than chronological age by two years or more).
      CONCLUSIONS: Morphofunctional characteristics in the studied groups of women
      demonstrate the trends of age-involutive changes which can be traced through all
      groups, from those with slow rates of aging, to those with average rates, to
      those with accelerated tempos of aging, and finally in long-lived women. The
      results of comparative analysis show that women with accelerated aging are
      characterized with such traits as lower skeletal muscle mass, lower hand grip
      strength, and higher metabolic rate. Canonical discriminant analysis revealed a
      number of morphofunctional characteristics which differentiate the early-aging
      women from women with average rates of aging: higher BMI values, excessive fat
      mass, lower skeletal muscle mass and low values of hand grip strength. Thus the
      presence of such characteristics in elderly women can be considered as additional
      risk factor towards the early onset of the aging process.

PMID- 24887212
TI  - Mind the gap: Concerns using endpoints from endocrine screening assays in risk
      assessment.
AB  - Endocrine screening assays not only provide mechanistic information on the
      potential of a substance to interact with the endocrine system, but also data
      potentially relevant for risk assessment. However, these screening assays have a
      number of limitations that should be considered before the direct use of such
      data for risk assessment purposes. This paper discusses the limitations that
      should be considered for both human and environmental risk assessment. A proposal
      is made to provide an objective and transparent process in order to consider
      which endpoint(s) might be incorporated into a risk assessment, and when more
      definitive studies may be of value. The proposal is complemented with an easy-to
      follow flowchart to aid industry scientists and regulators when evaluating the
      relevance of these data. Such an approach is necessary to ensure the appropriate
      use of screening data to further our understanding of the eco/toxicological
      profile of substances undergoing screening. 

PMID- 24887213
TI  - Anticoagulation therapy versus placebo for pulmonary hypertension.
AB  - BACKGROUND: Elevation of pulmonary pressure is no longer a rare disease, given
      its multifactorial etiology. However data on the actual incidence of this
      condition are still limited, and controversies regarding its management are
      ongoing. Use of anticoagulation in the management of pulmonary hypertension is
      based on the presence of in situ thrombosis in the patient with pulmonary
      arterial hypertension (PAH) and on retrospective evidence of clinical benefit.
      Current practice is dependent mostly on expert opinion and individualised
      experience. The real benefit of its use in different types of pulmonary
      hypertension is still debatable, and the therapeutic target of the international
      normalised ratio (INR) among treated patients remains inconclusive. Adverse
      outcomes associated with anticoagulants are significant and can include fatal
      haemorrhage. Justification for the use of this intervention requires critical
      evaluation of randomised controlled trials. OBJECTIVES: 1. To evaluate the
      effectiveness of, and potential adverse events associated with, anticoagulation
      in the management of pulmonary hypertension (PH).2. To evaluate the effective
      therapeutic INR in pulmonary hypertensive patients receiving anticoagulants
      (North American centres 1.5 to 2.5, European centres 2.0 to 3.0). SEARCH METHODS:
      We identified trials through searches of the following databases.Cochrane Airways
      Group Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL),
      part of The Cochrane Library; MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCOhost);
      Clinical trials.gov and the World Health Organization (WHO) trials portal. The
      trial search date was 28 March 2014. SELECTION CRITERIA: We planned to include
      only randomised controlled trials. Participants with PH with co-morbidities
      including medical conditions requiring long-term anticoagulation were to be
      included. We also planned to include trials comparing any anticoagulant with
      placebo. DATA COLLECTION AND ANALYSIS: Review authors (IE and HE) independently
      appraised all identified citations to establish their relevance for inclusion in
      the review. IE and HE independently screened the titles and abstracts of all
      identified potential studies for inclusion. MAIN RESULTS: No eligible trials were
      identified for inclusion in this review. AUTHORS' CONCLUSIONS: No eligible
      studies were identified for inclusion in this review. Although our review of
      available non-randomised studies shows beneficial effect, this finding should be
      interpreted with caution since there are likely to be biases associated with
      their design and our methods were not designed to identify, appraise and
      summarise evidence from them. So that better decisions can be made regarding the
      effectiveness of this intervention, well-designed randomised controlled trials
      are needed.

PMID- 24887214
TI  - An association study of CASQ1 gene polymorphisms and heat stroke.
AB  - Although molecular mechanisms of heat stroke under physiological and pathological
      conditions have not yet been elucidated, a novel disease-associated gene encoding
      a calcium-binding protein, calsequestrin-1 (CASQ1), was suggested relevant based
      on results from a transgenic murine model. Here, we show the association between
      single nucleotide polymorphisms (SNPs) of CASQ1 and physiological parameters for
      heat stroke from a study involving 150 patients. Pooled DNA from heat stroke
      patients were subjected to sequencing and 3 SNPs were identified. Genotypes were
      assigned for all patients according to g. 175A>G, one SNP which leads to a
      nonsynonymous substitution (N59D) in the first exon of human CASQ1 gene. We
      analyzed the genotypic data with a linear model based on significance scores
      between SNP (175A>G) and heat stroke parameters. As a result, we found a
      significant association between SNP A175G and heat stroke (P<0.05). Further
      bioinformatics analysis of the 1-Mb flanking sequence revealed the presence of
      two genes that encode DDB1 and CUL4 associated factor 8 (DCAF8), and peroxisomal
      biogenesis factor 19 (PEX19), respectively, which might be functionally related
      to CASQ1. Our results showed that the blood calcium of patients with allele D
      increased significantly, compared to patients with allele N (P<0.05), which may
      result from the decreased calcium in muscle, suggesting that N59D in CASQ1 might
      account for the dysfunction of CASQ1 in calcium regulation during heat stroke.

PMID- 24887215
TI  - Weighted-incidence syndromic combination antibiograms to guide empiric treatment
      of critical care infections: a retrospective cohort study.
AB  - INTRODUCTION: Empiric antimicrobial selection for critical care infections must
      balance the need for timely adequate coverage with the resistance pressure
      exerted by broadspectrum agents. We estimated the potential of weighted incidence
      syndromic combination antibiograms (WISCAs) to improve time to adequate coverage
      for critical care infections. In contrast to traditional antibiograms, WISCAs
      display the likelihood of coverage for a specific infectious syndrome (rather
      than individual pathogens), and also take into account the potential for poly
      microbial infections and the use of multi-drug regimens. METHODS: Cases of
      ventilator-associated pneumonia (VAP) and catheter-related bloodstream infection
      (CRBSI) were identified over three years using stringent surveillance criteria.
      Based on the susceptibility profile of the culprit pathogens, we calculated the
      WISCA percentages of infections that would have been adequately covered by common
      antimicrobial(s). We then computed the excess percentage coverage offered by
      WISCA regimens compared to the actual antimicrobials administered to patients by
      12 h, 24 h, and 48 h from culture collection. RESULTS: Among 163 patients with
      critical care infection, standard practice only resulted in adequate coverage of
      35% of patients by 12 h, 52% by 24 h, and 75% by 48 h. No WISCA mono-therapy
      regimen offered greater than 85% adequate overall coverage for VAP and CRBSI. A
      wide range of dual therapy regimens would have conferred greater than 90%
      adequate coverage, with excess coverage estimated to be as high as +56%, +42% and
      +18% at 12 h, 24 h and 48 h, respectively. We did not detect a decrease in
      mortality associated with early adequate treatment, and so could not estimate
      potential downstream benefits. CONCLUSIONS: WISCA-derived empiric antimicrobial
      regimens can be calculated for patients with intensive care unit (ICU)-acquired
      infections, and have the potential to reduce time to adequate treatment.
      Prospective research must confirm whether implementation of WISCA prescribing
      aids facilitate timely adequate treatment and improved ICU outcomes.

PMID- 24887216
TI  - Anti-IgA detection by particle gel immunoassay.

PMID- 24887218
TI  - Evaluation of an easy and affordable flow cytometer for volumetric haematopoietic
      stem cell counting.
AB  - BACKGROUND: Accurate estimation of haematopoietic stem cell (HSC) counts by flow
      cytometry may be difficult in laboratories in which sophisticated equipment and
      staff with specific expertise are not available. Affordable flow cytometers that
      can perform basic functions may help to overcome these difficulties. In this
      study we compared HSC and leucocyte counts determined by volumetric and bead
      based protocols performed with the small, low-cost Accuri((r)) C6, with those
      obtained with two gold-standard instruments, the four-colour FACSCalibur((r)) and
      the eight-colour FACSCantoII((r)), our reference flow cytometers. MATERIALS AND
      METHODS: With the three cytometers we tested, in parallel, 111 consecutive
      samples from cord blood, peripheral blood from patients with myelofibrosis and
      myeloproliferative syndromes, fresh and thawed HSC collected by apheresis and
      bone marrow products. The findings were compared with one-way ANOVA, Bland-Altman
      analysis and linear regression. RESULTS: The results of HSC and leucocyte
      enumeration by the three devices were strongly correlated (r(2)>0.99; p<0.0001).
      ANOVA performed on different subgroups of samples did not reveal significant
      differences between HSC count determined by the C6 bead-based and reference flow
      cytometers in any of the subgroups. Regarding the C6 volumetric protocol, a
      statistically significant difference was observed only in the cord blood
      subgroup. Time for instrument set-up, calibration and analysis was slightly
      longer with Accuri((r)) C6 (40 min) than with FACSCantoII((r)) (30 min).
      DISCUSSION: Accuri((r)) C6 is a reliable instrument for HSC enumeration in fresh
      samples, using both volumetric and bead-based approaches, although the volumetric
      protocol on cord blood samples needs to be improved. The Accuri((r)) C6 is easy
      to use, does not require profound knowledge of flow cytometry and could be
      employed in an urgent setting. Its performance may be improved by more efficient
      calibration and shorter analysis time.

PMID- 24887217
TI  - Incidence and pattern of 12 years of reported transfusion adverse events in
      Zimbabwe: a retrospective analysis.
AB  - BACKGROUND: Haemovigilance hinges on a systematically structured reporting
      system, which unfortunately does not always exist in resource-limited settings.
      We determined the incidence and pattern of transfusion-related adverse events
      reported to the National Blood Service Zimbabwe. MATERIALS AND METHODS: A
      retrospective review of the transfusion-event records of the National Blood
      Service Zimbabwe was conducted covering the period from 1 January 1999 to 31
      December 2011. All transfusion-related event reports received during the period
      were analysed. RESULTS: A total of 308 transfusion adverse events (0.046%) were
      reported for 670,625 blood components distributed. The majority (61.6%) of the
      patients who experienced an adverse event were female. The median age was 36
      years (range, 1-89 years). The majority (68.8%) of the adverse events were acute
      transfusion reactions consisting of febrile non-haemolytic transfusion reactions
      (58.5%), minor allergies (31.6%), haemolytic reactions (5.2%), severe allergic
      reactions (2.4%), anaphylaxis (1.4%) and hypotension (0.9%). Two-thirds (66.6%)
      of the adverse events occurred following administration of whole blood, although
      only 10.6% of the blood was distributed as whole blood. Packed cells, which
      accounted for 75% of blood components distributed, were associated with 20.1% of
      the events. DISCUSSION: The incidence of suspected transfusion adverse events was
      generally lower than the incidences reported globally in countries with well
      established haemovigilance systems. The administration of whole blood was
      disproportionately associated with transfusion adverse events. The pattern of the
      transfusion adverse events reported here highlights the probable differences in
      practice between different settings. Under-reporting of transfusion events is
      rife in passive reporting systems.

PMID- 24887220
TI  - Mixed field reactions in ABO and Rh typing chimerism likely resulting from twin
      haematopoiesis.

PMID- 24887219
TI  - The importance of antenatal prevention of RhD immunisation in the first
      pregnancy.
AB  - BACKGROUND: The aim of this study was to examine which pregnancies are associated
      with RhD immunisation and haemolytic disease of foetus and newborn (HDFN) when
      postnatal RhD prophylaxis is applied. MATERIAL AND METHODS: This retrospective
      cohort study included pregnancies with RhD immunisation; each of the pregnant
      women received anti-D immunoglobulin after delivery, miscarriage or invasive
      antenatal diagnostic procedures. For each pregnancy we analysed the order of
      pregnancy that caused immunisation as well as the order of the monitored
      pregnancy and whether the anti-D antibodies caused HDFN. RESULTS: Anti-D antibody
      was detected in 1.2% of RhD-negative pregnancies. Out of 89 monitored
      pregnancies, 56 (63%) were immunised by the first pregnancy, 21 (24%) by the
      second one, and 12 (13%) by subsequent pregnancies. HDFN occurred in 28 cases; 25
      of them were the consequence of the immunisation in the first pregnancy. The most
      severe cases of HDFN, perinatal death (n=2) and intrauterine transfusion (n=7)
      were consequence of immunisation during the first pregnancy. Significantly more
      cases of HDFN were caused by immunisation in the first pregnancy than by
      immunisation in subsequent pregnancies (chi(2)=12, p<0.01). CONCLUSION: RhD
      immunisation could be reduced in more than half cases by administering anti-D
      immunoglobulin at the beginning of the third trimester of pregnancy, especially
      the first pregnancy.

PMID- 24887221
TI  - ABO chimerism with a minor allele detected by the peptide nucleic acid-mediated
      polymerase chain reaction clamping method.

PMID- 24887222
TI  - Detection of anti-IgA antibodies using the particle gel immunoassay: a rapid test
      for increased patient safety.
AB  - BACKGROUND: Patient safety is a major issue in transfusion medicine and commands
      continuous efforts to develop valid control methods aiming to avoid serious
      transfusion-related complications. Anti-IgA antibodies can cause anaphylactic
      transfusion reactions in IgA-deficient individuals. Since standard quantitative
      methods for anti-IgA measurement require considerable time to be performed, in an
      emergency situation it can be a challenge to prevent or to quickly interpret and
      manage acute transfusion reactions suspected to be a consequence of anti-IgA. The
      purpose of this study was to test and validate at our transfusion centre a rapid
      assay for the identification of patients with anti-IgA antibodies. MATERIALS AND
      METHODS: Forty-six samples (6 from healthy controls and 40 from IgA-deficient
      patients) were collected. Sera were analysed blindly by three different clinical
      laboratory technologists using two DiaMed particle gel immunoassays (ID-PaGIA)
      for IgA deficiency and for antibodies to IgA. The results were subsequently
      checked with the results of a fluorescence enzyme immunoassay conducted in the
      reference immunology laboratory. RESULTS: The ID-PaGIA had a sensitivity of 91.7%
      and specificity of 97.1% for the IgA deficiency test. With regards to the
      detection of anti-IgA antibodies, the sensitivity was 89.3% and the specificity
      100%. The reproducibility of the test was 100%. DISCUSSION: The ID-PaGIA
      screening assays are suitable for the investigation of transfusion-related
      anaphylactic reactions in a routine blood bank laboratory. Although the gel card
      technique does not quantify the level of anti-IgA antibodies, it is readily
      available, providing an effective and simple method for the diagnosis of anti-IgA
      related anaphylaxis and guidance for the appropriate transfusion practice in an
      emergency.

PMID- 24887223
TI  - Contribution of damage-associated molecular patterns to transfusion-related acute
      lung injury in cardiac surgery.
AB  - BACKGROUND: The incidence of transfusion-related acute lung injury (TRALI) in
      cardiac surgery patients is high and this condition contributes to an adverse
      outcome. Damage-associated molecular pattern (DAMP) molecules, HMGB1 and S100A12,
      are thought to mediate inflammatory changes in acute respiratory distress
      syndrome. We aimed to determine whether DAMP are involved in the pathogenesis of
      TRALI in cardiac surgery patients. MATERIALS AND METHODS: This was a secondary
      analysis of a prospective observational trial in cardiac surgery patients
      admitted to the Intensive Care Unit of a university hospital in the Netherlands.
      Fourteen TRALI cases were randomly matched with 32 transfused and non-transfused
      controls. Pulmonary levels of HMGB1, S100A12 and inflammatory cytokines
      (interleukins-1beta, -6, and -8 and tumour necrosis factor-alpha) were determined
      when TRALI evolved. In addition, systemic and pulmonary levels of soluble
      receptor for advanced glycation end products (sRAGE) were determined. RESULTS:
      HMGB1 expression and levels of sRAGE in TRALI patients did not differ from those
      in controls. There was a trend towards higher S100A12 levels in TRALI patients
      compared to the controls. Furthermore, S100A12 levels were associated with
      increased levels of markers of pulmonary inflammation, prolonged cardiopulmonary
      bypass, hypoxemia and duration of mechanical ventilation. CONCLUSION: No evidence
      was found that HMGB1 and sRAGE contribute to the development of TRALI. S100A12 is
      associated with duration of cardiopulmonary bypass, pulmonary inflammation,
      hypoxia and prolonged mechanical ventilation and may contribute to acute lung
      injury in cardiac surgery patients.

PMID- 24887225
TI  - Reciprocal absence of cross-resistance between eltrombopag and romiplostim in two
      patients with refractory immune thrombocytopenic purpura.

PMID- 24887224
TI  - Antibodies reacting with Simian virus 40 mimotopes in serum samples from patients
      with thalassaemia major.
AB  - BACKGROUND: Simian virus 40 (SV40) is a small DNA tumour virus. Footprints of the
      virus have been detected in different humam lymphoproliferative disorders and in
      blood specimens of blood from healthy blood donors. This study was carried out to
      verify whether SV40 antibodies can be detected in serum samples from multiply
      transfused patients with thalassaemia major. MATERIALS AND METHODS: An indirect
      enzyme-linked immunosorbent assay was employed, using SV40 specific synthetic
      peptides mimicking the antigens of the viral capsid proteins 1-2-3, to test for
      the presence of antibodies to SV40 in serum samples taken from patients affected
      by transfusion-dependent thalassaemia major (n=190) and healthy blood donors
      (n=251). RESULTS: The prevalence of antibodies against SV40 was higher in
      patients than in controls (24% vs 17%). The prevalence increased and was
      significantly higher in the older age group of patients affected by thalassemia
      major than in controls (38% vs 20%, p<0.04). DISCUSSION: The higher prevalence of
      serum antibodies against simian virus 40 in older, multiply transfused patients
      with thalassamia major than in controls suggests that this virus, or a closely
      related yet unknown human polyomavirus, could have been transmitted in the past
      by transfusion with whole blood. At the same time, our data indicate no
      significant differences in prevalence of SV40 antibodies in patients and controls
      of younger age thus suggesting that current transfusion methods with
      leucodepletion and filtered red cells are safe.

PMID- 24887226
TI  - Efficacy of combined intravenous immunoglobulins and steroids in children with
      primary immune thrombocytopenia and persistent bleeding symptoms.
AB  - BACKGROUND: The aim of this study was to investigate the effect of the combined
      administration of intravenous immunoglobulins and steroids as a second-line
      therapy in 34 children with primary immune thrombocytopenia and persistent,
      symptomatic bleeding. MATERIALS AND METHODS: Combined therapy (intravenous
      immunoglobulins 0.4 g/kg daily on days 1 and 2, and methylprednisolone 20 mg/kg
      daily on days 1-3) was administered to 12 patients with newly diagnosed ITP who
      did not respond to the administration of a single therapy (either intravenous
      immunoglobulins or steroids) and to 22 children with persistent and chronic
      disease who required frequent administrations (i.e. more frequently than every 30
      days) of either immunoglobulins or steroids (at the same standard dosages) in
      order to control active bleeding. RESULTS: A response (i.e. platelet count
      >50*10(9)/L and remission of active bleeding) was observed in 8/12 (67%) patients
      with newly diagnosed ITP. The clinical presentation of responders and non
      responders did not differ apparently. Patients in the chronic/persistent phase of
      disease had a significantly longer median period of remission from symptoms
      compared with the previous longest period of remission (p=0.016). The treatment
      was well tolerated. DISCUSSION: Our data suggest that the combined approach
      described is a well-tolerated therapeutic option for children with primary immune
      thrombocytopenia and persistent bleeding symptoms that can be used in both
      emergency and/or maintenance settings.

PMID- 24887227
TI  - Dramatic post-splenectomy onset of malaria caused by latent Plasmodium vivax in a
      female immigrant with severe immunological anaemia.

PMID- 24887228
TI  - Severe drug-induced immune haemolytic anaemia due to ceftazidime.

PMID- 24887229
TI  - Attitudes and behaviours of Greeks concerning blood donation: recruitment and
      retention campaigns should be focused on need rather than altruism.
AB  - BACKGROUND: Blood supplies in Greece are insufficient to meet the high
      transfusion needs arising from car accidents and treatment of thalassaemia. This
      study was designed to determine Greeks' opinions about blood donation, in order
      to identify the reasons for the lack of motivation to donate and allow experts to
      establish better recruitment campaigns for the enrichment of the donor pool,
      based on our findings. MATERIALS AND METHODS: The opinions of randomly selected
      Greek citizens (n=800) about volunteer blood donation were assessed by means of a
      standardised, anonymous questionnaire. The results were analysed using the chi(2)
      test and Spearman's correlation coefficient. RESULTS: With regards to attitudes
      towards intention to donate, only 7.1% were indifferent, while 88.0% of the
      individuals believed that donating blood was an "offer". Reasons for not donating
      mainly involved safety (36.0%) and fear (24.0%), whereas need (77.9%) was the
      most fundamental positive motivation. Of the people enrolled in the present
      study, 10.0% were active donors, 31.3% occasional donors, 15.0% rare donors and
      36.6% non-donors. DISCUSSION: The considerable percentages of occasional and rare
      donors in comparison with the low proportion of active donors in the Greek donor
      pool indicates that "need" is a more important motivation for blood donation than
      altruism in Greece. These results could be useful for establishing advertising
      campaigns on blood donation and for a more direct approach to the population,
      aiming for a change in mentality in favour of active blood donation.

PMID- 24887230
TI  - Bacterial screening of platelet concentrates on day 2 and 3 with flow cytometry:
      the optimal sampling time point?
AB  - BACKGROUND: There is growing concern on the residual risk of bacterial
      contamination of platelet concentrates in Germany, despite the reduction of the
      shelf-life of these concentrates and the introduction of bacterial screening. In
      this study, the applicability of the BactiFlow flow cytometric assay for
      bacterial screening of platelet concentrates on day 2 or 3 of their shelf-life
      was assessed in two German blood services. The results were used to evaluate
      currently implemented or newly discussed screening strategies. MATERIALS AND
      METHODS: Two thousand and ten apheresis platelet concentrates were tested on day
      2 or day 3 after donation using BactiFlow flow cytometry. Reactive samples were
      confirmed by the BacT/Alert culture system. RESULTS: Twenty-four of the 2,100
      platelet concentrates tested were reactive in the first test by BactiFlow. Of
      these 24 platelet concentrates, 12 were false-positive and the other 12 were
      initially reactive. None of the microbiological cultures of the initially
      reactive samples was positive. Parallel examination of 1,026 platelet
      concentrates by culture revealed three positive platelet concentrates with
      bacteria detected only in the anaerobic culture bottle and identified as
      Staphylococcus species. Two platelet concentrates were confirmed positive for
      Staphylcoccus epidermidis by culture. Retrospective analysis of the growth
      kinetics of the bacteria indicated that the bacterial titres were most likely
      below the diagnostic sensitivity of the BactiFlow assay (<300 CFU/mL) and
      probably had no transfusion relevance. CONCLUSIONS: The BactiFlow assay is very
      convenient for bacterial screening of platelet concentrates independently of the
      testing day and the screening strategy. Although the optimal screening strategy
      could not be defined, this study provides further data to help achieve this goal.

PMID- 24887231
TI  - Matching for the D antigen in haematopoietic progenitor cell transplantation:
      definition and clinical outcomes.

PMID- 24887232
TI  - Rapid diagnosis of Streptococcus pneumoniae-induced haemolytic-uraemic syndrome.

PMID- 24887234
TI  - Investigation of supramolecular synthons and structural characterisation of
      aminopyridine-carboxylic acid derivatives.
AB  - BACKGROUND: Co-crystal is a structurally homogeneous crystalline material that
      contains two or more neutral building blocks that are present in definite
      stoichiometric amounts. The main advantage of co-crystals is their ability to
      generate a variety of solid forms of a drug that have distinct physicochemical
      properties from the solid co-crystal components. In the present investigation,
      five co-crystals containing 2-amino-6-chloropyridine (AMPY) moiety were
      synthesized and characterized. RESULTS: The crystal structure of 2-amino-6
      chloropyridine (AMPY) (I), and the robustness of pyridine-acid supramolecular
      synthon were discussed in four stoichiometry co-crystals of AMPY...BA (II),
      AMPY...2ABA (III), AMPY...3CLBA (IV) and AMPY...4NBA (V). The abbreviated
      designations used are benzoic acid (BA), 2-aminobenzoic acid (2ABA), 3
      chlorobenzoic acid (3CLBA) and 4-nitrobenzoic acid (4NBA). All the crystalline
      materials have been characterized by (1)HNMR, (13)CNMR, IR, photoluminescence,
      TEM analysis and X-ray diffraction. The supramolecular assembly of each co
      crystal is analyzed and discussed. CONCLUSIONS: Extensive N---H . . . N/N---H . .
      . O/O---H . . . N hydrogen bonds are found in (I-V), featuring different
      supramolecular synthons. In the crystal structure, for compound (I), the 2-amino
      6-chloropyridine molecules are linked together into centrosymmetric dimers by
      hydrogen bonds to form homosynthon, whereas for compounds (II-V), the carboxylic
      group of the respective acids (benzoic acid, 2-aminobenzoic acid, 3-chlorobenzoic
      acid and 4-nitrobenzoic acid) interacts with pyridine molecule in a linear
      fashion through a pair of N---H . . . O and O---H . . . N hydrogen bonds,
      generating cyclic hydrogen-bonded motifs with the graph-set notation [Formula:
      see text] , to form heterosynthon. In compound (II), another intermolecular N---H
      . . . O hydrogen bonds further link these heterosynthons into zig-zag chains.
      Whereas in compounds (IV) and (V), these heterosynthons are centrosymmetrically
      paired via N---H . . . O hydrogen bonds and each forms a complementary DADA [D =
      donor and A = acceptor] array of quadruple hydrogen bonds, with graph-set
      notation [Formula: see text], [Formula: see text] and [Formula: see text].

PMID- 24887233
TI  - Sickle cell disease in areas of immigration of high-risk populations: a low cost
      and reproducible method of screening in northern Italy.
AB  - BACKGROUND: From 2005 to 2010, we observed a 10-fold increase of newly diagnosed
      sickle cell disease in children in the province of Modena (northern Italy). The
      median age at diagnosis was 24 months. Since these children are too old for
      optimal disease management, earlier detection of the disease is needed for
      prophylaxis and comprehensive care before the occurrence of clinical
      manifestations. MATERIALS AND METHODS: In each Maternity Unit of the province of
      Modena, blood samples are collected daily for assessment of haemolytic disease of
      the newborn. We designed a selective, low-cost haemoglobin screening for sickle
      cell disease in high-risk immigrants. We enrolled 469 mothers from sub-Saharan
      countries and their neonates for a primary screening of peripheral blood
      haemoglobin variants using high-performance liquid chromatography. RESULTS: Of
      the 469 women approached, 330 (70.36%) agreed to undergo the test. Ninety-two
      (27.88%) were carriers of variant haemoglobin, 48 newborns (51%) of these
      carriers had the carrier trait and 9 (9.6%) were affected (haemoglobin SC
      compound heterozigote - HbSC, haemoglobin S homozygote - HbSS). DISCUSSION: These
      results support the feasibility and usefulness of a selective screening for the
      detection of haemoglobin variants in high-risk subjects in an area in which
      sickle cells disease is not endogenous. We achieved the goal of detecting
      subjects with carrier trait/disease in order to implement preventive measures
      that reduce the clinical manifestations of sickle cell disease. We are, however,
      aware that it will be necessary to extend this screening to the overall
      population in the near future.

PMID- 24887235
TI  - Ligand-independent canonical Wnt activity in canine mammary tumor cell lines
      associated with aberrant LEF1 expression.
AB  - Pet dogs very frequently develop spontaneous mammary tumors and have been
      suggested as a good model organism for breast cancer research. In order to obtain
      an insight into underlying signaling mechanisms during canine mammary
      tumorigenesis, in this study we assessed the incidence and the mechanism of
      canonical Wnt activation in a panel of 12 canine mammary tumor cell lines. We
      show that a subset of canine mammary cell lines exhibit a moderate canonical Wnt
      activity that is dependent on Wnt ligands, similar to what has been described in
      human breast cancer cell lines. In addition, three of the tested canine mammary
      cell lines have a high canonical Wnt activity that is not responsive to
      inhibitors of Wnt ligand secretion. Tumor cell lines with highly active canonical
      Wnt signaling often carry mutations in key members of the Wnt signaling cascade.
      These cell lines, however, carry no mutations in the coding regions of
      intracellular Wnt pathway components (APC, beta-catenin, GSK3beta, CK1alpha and
      Axin1) and have a functional beta-catenin destruction complex. Interestingly,
      however, the cell lines with high canonical Wnt activity specifically overexpress
      LEF1 mRNA and the knock-down of LEF1 significantly inhibits TCF-reporter
      activity. In addition, LEF1 is overexpressed in a subset of canine mammary
      carcinomas, implicating LEF1 in ligand-independent activation of canonical Wnt
      signaling in canine mammary tumors. We conclude that canonical Wnt activation may
      be a frequent event in canine mammary tumors both through Wnt ligand-dependent
      and novel ligand-independent mechanisms. 

PMID- 24887238
TI  - Physicians and politics.

PMID- 24887236
TI  - Epidermal growth factor-receptor activation modulates Src-dependent resistance to
      lapatinib in breast cancer models.
AB  - INTRODUCTION: Src tyrosine kinase overactivation has been correlated with a poor
      response to human epidermal growth factor receptor 2 (HER2) inhibitors in breast
      cancer. To identify the mechanism by which Src overexpression sustains this
      resistance, we tested a panel of breast cancer cell lines either sensitive or
      resistant to lapatinib. METHODS: To determine the role of Src in lapatinib
      resistance, we evaluated the effects of Src inhibition/silencing in vitro on
      survival, migration, and invasion of lapatinib-resistant cells. In vivo
      experiments were performed in JIMT-1 lapatinib-resistant cells orthotopically
      implanted in nude mice. We used artificial metastasis assays to evaluate the
      effect of Src inhibition on the invasiveness of lapatinib-resistant cells. Src
      dependent signal transduction was investigated with Western blot and ELISA
      analyses. RESULTS: Src activation was higher in lapatinib-resistant than in
      lapatinib-sensitive cells. The selective small-molecule Src inhibitor saracatinib
      combined with lapatinib synergistically inhibited the proliferation, migration,
      and invasion of lapatinib-resistant cells. Saracatinib combined with lapatinib
      significantly prolonged survival of JIMT-1-xenografted mice compared with
      saracatinib alone, and impaired the formation of lung metastases. Unexpectedly,
      in lapatinib-resistant cells, Src preferentially interacted with epidermal growth
      factor receptor (EGFR) rather than with HER2. Moreover, EGFR targeting and
      lapatinib synergistically inhibited survival, migration, and invasion of
      resistant cells, thereby counteracting Src-mediated resistance. These findings
      demonstrate that Src activation in lapatinib-resistant cells depends on EGFR
      dependent rather than on HER2-dependent signaling. CONCLUSIONS: Complete
      pharmacologic EGFR/HER2 inhibition is required to reverse Src-dependent
      resistance to lapatinib in breast cancer.

PMID- 24887237
TI  - Prevalence and characterization of enterovirus infections among pediatric
      patients with hand foot mouth disease, herpangina and influenza like illness in
      Thailand, 2012.
AB  - Hand, foot, and mouth disease (HFMD) and herpangina are common infectious
      diseases caused by several genotypes of human enterovirus species A and
      frequently occurring in young children. This study was aimed at analyzing
      enteroviruses from patients with these diseases in Thailand in 2012. Detection
      and genotype determination of enteroviruses were accomplished by reverse
      transcription-polymerase chain reaction and sequencing of the VP1 region.
      Enterovirus-positive samples were differentiated into 17 genotypes
      (coxsackievirus A4 (CAV4), A5, A6, A8, A9, A10, A12, A16, A21, B1, B2, B4, B5,
      echovirus 7, 16, 25 and Enterovirus 71). The result showed CAV6 (33.5%), followed
      by CAV16 (9.4%) and EV71 (8.8%) as the most frequent genotypes in HFMD, CAV8
      (19.3%) in herpangina and CAV6 (1.5%) in influenza like illness. Enterovirus
      infections were most prevalent during July with 34.4% in HFMD, 39.8% in
      herpangina and 1.6% in ILI. The higher enterovirus infection associated with HFMD
      and herpangina occurred in infants over one year-old. This represents the first
      report describing the circulation of multiple enteroviruses in Thailand. 

PMID- 24887239
TI  - Nasal saline irrigation in preschool children: a survey of attitudes and
      prescribing habits of primary care pediatricians working in northern Italy.
AB  - BACKGROUND: It has been shown that nasal saline irrigation (NSI) alone can be
      effective in children with infectious and/or allergic respiratory problems, but
      no study has assessed the awareness or clinical use of NSI among practising
      pediatricians. The main aim of this study was to evaluate the use of NSI in pre
      school children by primary care pediatricians working in northern Italy. METHODS:
      Nine hundred randomly selected National Health Service primary care pediatricians
      with an e-mail address were sent an e-mail asking whether they were willing to
      respond to a questionnaire regarding the use of NSI. The 870 who answered
      positively were sent an anonymous questionnaire by post and e-mail that had 17
      multiple-choice items. RESULTS: Completed questionnaires were received from 860
      of the 870 primary care pediatricians (98.8%). NSI was used by almost all the
      respondents (99.3%), although with significant differences in frequency. It was
      considered both a prophylactic and a therapeutic measure by most of the
      respondents (60.3%), who prescribed it every day for healthy children and more
      frequently when they were ill. Most of the primary care pediatricians (87%)
      indicated an isotonic solution as the preferred solution, and the most frequently
      recommended administration devices were a nasal spray (67.7%) and bulb syringe
      (20.6%). Most of the pediatricians (75.6%) convinced parents to use NSI by
      explaining it could have various beneficial effects, and two-thirds (527/854;
      61.7%) thought that most of the parents agreed about the importance of NSI.
      Analysis of possible associations between NSI prescribing behaviour and the
      demographic data revealed an associations with age and gender, with pediatricians
      aged <50 years prescribing NSI more frequently than their older counterparts (p <
      0.01), and females prescribing NSI more frequently than males (p < 0.01).
      CONCLUSIONS: In Northern Italy, most primary care pediatricians prescribe NSI for
      both the prophylaxis and therapy of upper respiratory tract problems in pre
      school children. However, many aspects of the procedure are not clarified, and
      this reduces parental compliance. Given the medical and economic advantages of
      NSI, this situation should be changed as soon as possible.

PMID- 24887240
TI  - Preparation, characterization and in vitro efficacy of magnetic nanoliposomes
      containing the artemisinin and transferrin.
AB  - BACKGROUND: Artemisinin is the major sesquiterpene lactones in sweet wormwood
      (Artemisia annua L.), and its combination with transferrin exhibits versatile
      anti-cancer activities. Their non-selective targeting for cancer cells, however,
      limits their application. The aim of this study was to prepare the artemisinin
      and transferrin-loaded magnetic nanoliposomes in thermosensitive and non
      thermosensitive forms and evaluate their antiproliferative activity against MCF-7
      and MDA-MB-231 cells for better tumor-targeted therapy. METHODS: Artemisinin and
      transferrin-loaded magnetic nanoliposomes was prepared by extrusion method using
      various concentrations of lipids. These formulations were characterized for
      particle size, zeta potential, polydispersity index and shape morphology. The
      artemisinin and transferrin-loading efficiencies were determined using HPLC. The
      content of magnetic iron oxide in the nanoliposomes was analysed by
      spectrophotometry. The in vitro release of artemisinin, transferrin and magnetic
      iron oxide from vesicles was assessed by keeping of the nanoliposomes at 37
      degrees C for 12 h. The in vitro cytotoxicity of prepared nanoliposomes was
      investigated against MCF-7 and MDA-MB-231 cells using MTT assay. RESULTS: The
      entrapment efficiencies of artemisinin, transferrin and magnetic iron oxide in
      the non-thermosensitive nanoliposomes were 89.11% +/- 0.23, 85.09% +/- 0.31 and
      78.10% +/- 0.24, respectively. Moreover, the thermosensitive formulation showed a
      suitable condition for thermal drug release at 42 degrees C and exhibited high
      antiproliferative activity against MCF-7 and MDA-MB-231 cells in the presence of
      a magnetic field. CONCLUSIONS: Our results showed that the thermosensitive
      artemisinin and transferrin-loaded magnetic nanoliposomes would be an effective
      choice for tumor-targeted therapy, due to its suitable stability and high
      effectiveness.

PMID- 24887241
TI  - Efficacy of ultrasound-guided radial artery catheterization: a systematic review
      and meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: Ultrasound guidance has emerged as an adjunct for central vein
      catheterization in both adults and children. However, the use of ultrasound
      guidance for radial arterial catheterization has not been well established. We
      conducted a systematic review and meta-analysis to evaluate the efficacy of
      ultrasound guidance for radial artery catheterization. METHODS: PubMed, Embase,
      and the Cochrane Central Register of Controlled Trials were searched. Randomized
      controlled trials (RCTs) comparing ultrasound guidance with other techniques
      (palpation or Doppler) in adult or pediatric patients requiring radial artery
      catheterization were included. The primary outcome was first-attempt success.
      RESULTS: Seven RCTs enrolling 546 patients met the inclusion criteria, and all
      the selected trials were considered as at high risk of bias. Ultrasound-guided
      radial artery catheterization was associated with an increased first-attempt
      success (relative risk (RR) 1.55, 95% confidence interval (CI) 1.02 to 2.35).
      There was significant heterogeneity among the studies (I2 = 74%). Ultrasound
      guided radial artery catheterization in small children and infants also provided
      an increased chance for first-attempt success (RR 1.94, 95% CI 1.31 to 2.88).
      Ultrasound guidance further significantly reduced mean attempts to success
      (weighted mean difference (WMD) -1.13, 95% CI -1.58 to -0.69), mean time to
      success (WMD -72.97 seconds, 95% CI -134.41 to -11.52), and incidence of the
      complication of hematoma (RR 0.17, 95% CI 0.07 to 0.41). CONCLUSIONS: Ultrasound
      guidance is an effective and safe technique for radial artery catheterization,
      even in small children and infants. However, the results should be interpreted
      cautiously due to the heterogeneity among the studies.

PMID- 24887242
TI  - Effect of novobiocin on the viability of human gingival fibroblasts (HGF-1).
AB  - BACKGROUND: Novobiocin is a coumarin antibiotic, which affects also eukaryotic
      cells inhibiting activity of Heat shock protein 90 (Hsp90). The Hsp90 represents
      a molecular chaperone critical for stabilization and activation of many proteins,
      particularly oncoproteins that drive cancer progression. Currently, Hsp90
      inhibitors focus a significant attention since they form a potentially new class
      of drugs in therapy of cancer. However, in the process of tumorigenesis a
      significant role is played also by the microenvironment of the tumour, and, in
      particular, by cancer-associated fibroblasts (CAFs). This study aimed at
      examination of the effect played by novobiocin on viability of human gingival
      fibroblasts (HGF-1). METHODS: The studies were conducted using 24 h cultures of
      human gingival fibroblasts - HGF-1 (CRL-2014) in Chamber Slides, in presence of
      0.1, 0.5, 1.0, 2.5 or 5.0 mM novobiocin. Cell viability was evaluated using
      fluorescence test, ATP assay and LDH release. RESULTS: Viability of HGF-1 was
      drastically reduced after 5 hour treatment with novobiocin in concentrations of 1
      mM or higher. In turn, the percentage of LDH-releasing cells after 5 h did not
      differ from control value although it significantly increased after 10 h
      incubation with 1 mM and continued to increase till the 20th hour. CONCLUSIONS:
      The obtained data indicate that novobiocin may induce death of human gingival
      fibroblasts. Therefore, application of the Hsp90 inhibitor in neoplastic therapy
      seems controversial: on one hand novobiocin reduces tumour-associated CAFs but,
      on the other, it may induce a significant destruction of periodontium.

PMID- 24887243
TI  - Missed injuries in trauma associated mortalities in a Nigerian teaching hospital.
AB  - AIMS AND OBJECTIVES: The objective of this study is to describe the pattern of
      missed injuries in trauma associated mortalities in the University College
      Hospital Ibadan Nigeria and to determine the relevance of postmortem examination
      in trauma related death. SUBJECTS AND METHODS: All cases of trauma- associated
      death in the Accident and Emergency Department of the University College Hospital
      (UCH), Ibadan Nigeria over a ten year period from January 1997 to December 2006
      were reviewed. Data extracted from the records included the demographic data, the
      mechanism of injury, time and duration of injury prior to presentation and the
      clinical diagnosis. The autopsy findings were compared to the clinical diagnosis
      by the medical officer in the emergency department. The unrecorded injuries noted
      at autopsy were reviewed and classified using the modified Goldman criteria for
      autopsy discrepancies RESULTS: Two hundred and ninety trauma related autopsies
      were performed within the stipulated period. Diagnostic errors were observed in
      fifty five (18.9%) of these autopsies. The commonest mechanism of injury was road
      traffic accident (73%). Thirty (57%) of these patients arrived at the ED within
      six hours of injury. There were 79 missed injuries consisting of chest injuries
      (43%), while 26% were abdominal injuries. There were 25 type 1 and 25 type 2
      major errors. The mean revised trauma score (RTS) at presentation was 4.81 +/-
      1.9 with a probability of survival of >60% CONCLUSION Trauma care needs to be
      taught as a specialty. Post mortem remains a necessary quality control tool.

PMID- 24887244
TI  - Lung function indices of flour millworkers in Edo and Delta States.
AB  - AIMS AND OBJECTIVES Flour dust has been associated with lung function impairment
      and Chronic Obstructive Airway Disease (COAD) among grain workers. This study was
      therefore conducted to assess the lung function indices of flour mill workers in
      Edo and Delta states, of Nigeria. MATERIALS AND METHODS Comparative cross
      sectional study designed was utilized for the study and it was carried out over a
      period of six months, (Nov 2010 to May 2011) among 200 flour mill workers and 200
      hospital workers in Edo and Delta states.A modified Medical Research Council
      (MRC) questionnaire which was interviewer administered and an electronic hand
      held spirometer was used to collect data. Data analysis was carried out using
      Statistical Package for Scientific Solution (SPSS) version 17. RESULTS: The Peak
      Expiratory Flow Rate (PEFR) of the flour dust exposed workers was significantly
      lower (p<0.001) compared to that of the unexposed population. All other lung
      function parameters were also lower although not statistically significant.
      CONCLUSION: Flour dust exposed workers in Edo Delta states like grain workers
      elsewhere have lung impairment, hence the need to provide protective equipment
      and also carry out regular periodic medical checks.

PMID- 24887245
TI  - Evaluation of a health resources management course for Nigerian doctors.
AB  - AIMS AND OBJECTIVES: This study aimed to evaluate the March 2010 edition of the
      regular biannual two-week course on health resources management organised by the
      National Postgraduate Medical College of Nigeria. The main objectives were to
      assess participants' perception of the course and to measure change in their
      knowledge brought about by the course. SUBJECTS AND METHODS: This is a primarily
      cross-sectional study but with a before and after component. The study population
      comprised all participants who attended the course. Data were collected using pre
      tested structured self- administered questionnaires. Data analysis was done with
      Epi Info 3.5.1. Student's T-test was used to compare mean scores at pre-test and
      post-test and the p-value of <0.05 was considered statistically significant.
      RESULTS: Majority (95.8%) of the participants were senior registrars from
      teaching hospitals and most of them (70.5%) claimed the course met their needs a
      great deal/to a large extent. The participants were satisfied to a varying degree
      with different aspects of the course but overall 50.9% claimed they got value for
      their money. There was a statistically significant difference in the knowledge
      score at pre- and post-test (t = 3.19, p = 0.002). CONCLUSION: The course met the
      needs of the participants largely and was able to improve their knowledge of
      health resources management as intended. A behaviour evaluation is recommended in
      order to assess the usefulness of the course to participants' practice.

PMID- 24887246
TI  - The seroprevalence of hepatitis C virus antibodies among transfused patients with
      haematological disorders.
AB  - AIMS AND OBJECTIVES: This study was undertaken to determine the prevalence of
      hepatitis C virus antibodies (anti- HCV) among transfused patients with
      haematological disorders. and correlate this with the units of blood or blood
      products received PATIENTS AND METHODS: This was a cross sectional study.
      Patients with haematological disorders who had received two or more units of
      blood or blood products and healthy blood donors who had not received blood
      transfusion were screened for ant-HCV using Enzyme Linked Immunosorbent Assay
      (ELISA) kits. RESULTS: A total of 480 subjects comprising 146 patients with
      haematological disorders and 334 blood donor controls were recruited for this
      study. The patients comprised 78 (53.4%) males and 68 (46.6%) females with age
      range from 14-65 years and a mean of 39.5. The prevalence of anti-HCV was 6
      (4.1%) among transfused patients and 7 (2.1%) among untransfused blood donors.
      The risk of anti- HCV positivity among patients was higher with increasing units
      of received blood or blood products. A significant statistical association was
      observed between the number of pints of blood or blood products received and anti
      HCV positivity among patients p=0.008 CONCLUSION: This study suggests that
      patients who had received blood or blood products are at higher risk of HCV
      infection than the untransfused individuals. The risk of infection is higher with
      increasing units of blood or blood products received by transfused patients.

PMID- 24887247
TI  - Blood donation practices and willingness to donate among residents of an urban
      slum in Lagos Nigeria.
AB  - AIM AND OBJECTIVES: This study was carried out to assess the blood donation
      practices and willingness to donate among residents of an urban slum. MATERIAL
      AND METHODS: Cross sectional descriptive study design with a qualitative and
      quantitative component. Multistage sampling was used to select 400 respondents
      for the questionnaire interview while three FGD sessions were conducted guide
      among three groups of participants namely youths, men and women. The information
      collected was analyzed manually (FGD) and with Epi info version 3.5.3. RESULTS:
      Majority of the questionnaire respondents were female, married, traders, had at
      least secondary school education, with mean age of 37.6 years. Only 12.0% had
      donated in the past, the main reason given by non donors was that they had never
      been asked to donate; this was also a key finding in the FGD. Willingness to
      donate was positively associated with being a male, single and Christian, age was
      a significant predictor of previous donation while more of the previous donors
      were still willing to donate, more for family/friends (p=0.036) than voluntarily
      (p=0.001) this view was supported by the participants at the FGD. CONCLUSION:
      Members of this urban slum had poor practice of blood donation,had positive
      attitude and were willing to donate, there is need to mobilise and organise
      outreach blood donation programs to convert attitude into actual practice.

PMID- 24887249
TI  - Grandmultiparity: evaluating obstetric and neonatal outcomes after eliminating
      confounders.
AB  - AIMS AND OBJECTIVES: The objective was to evaluate obstetric and neonatal
      outcomes in booked grandmultiparas (para e"5) and compare with outcome in age and
      social status matched booked multiparas (para 2-4) after eliminating confounders.
      PATIENTS AND METHODS: A cohort study with grandmultiparas (subjects) and age and
      social status matched multiparas as controls. All participants were counseled and
      an informed consent obtained at the antenatal clinic. Maternal demography and
      history were taken; they were subsequently monitored during pregnancy, labour and
      immediate puerperium. The main outcome measures were obstetric and neonatal
      outcomes among subjects and controls. RESULTS: The incidence of grandmultiparity
      was 4.1%. During antenatal period, grandmultiparas had statistically
      significantly higher occurrence of late antenatal booking (P=0.0202), anaemia
      (P=0.0024) and past history of poor perinatal outcome (P=0.0124). Grandmultiparas
      had statistically significant occurrence of preterm delivery (P=0.0389) and
      higher but not statistically significant mean duration of labour (P=0.3532),
      intrapartum complications (P=0.2014) and postpartum haemorrhage (P=0.2126).
      Neonates of grandmultiparas had statistically significant low first minute Apgar
      scores (P=0.0011) with higher but not statistically significant occurrence of low
      birth weight (P=0.1613) and neonatal intensive care admission (P=0.7202). The
      perinatal mortality rates were 136 and 75 per 1 000 deliveries for
      grandmultiparas and multiparas. There were no maternal deaths during the study
      period. CONCLUSION: After controlling for age and social class, booked
      grandmultiparas had poorer obstetric and neonatal outcome compared to booked
      multiparas but these were majorly statistically insignificant due to effect of
      modern antenatal care.

PMID- 24887248
TI  - Radiation dose and radiation protection principle awareness: a survey among
      Nigerian paediatricians.
AB  - AIMS AND OBJECTIVES: This study is aimed at determining the knowledge of
      Paediatricians in Nigeria about the basic principle of radiation protection ALARA
      (As Low As Reasonably Achievable) and their knowledge of the radiation doses that
      children receive during some common radiological procedures. MATERIALS AND
      METHODS: Two hundred and fifty questionnaires were circulated among
      paediatricians at the 2012 annual Paediatricians' Association of Nigeria
      Conference. The questionnaires contain 10 questions designed to asses the
      pediatricians' general knowledge on : ionising radiation and the risks, doses
      children receive during some common radiological procedures and awareness of the
      radiation protection principle, ALARA ( As Low As Reasonably Achievable).
      RESULTS: Of the 162 Paediatricians that participated, 69% named at least one non
      medical source of ionising radiation, 54.9% would not recommend CXR to screen an
      apparently healthy child for tuberculosis and 87% believe that children are at
      greater risk of adverse effects of ionising radiation. For dose estimation, 51.9%
      and 51.2% of the paediatricians underestimated doses received during Cranial and
      abdominal computerised tomography respectively while 13.6% and 37% respectively
      erroneously believed that abdominal ultrasound and brain magnetic resonance
      imaging utilise ionising radiation. 13.6% gave the correct meaning of the Acronym
      ALARA. CONCLUSIONS: The Paediatricians' knowledge about the basic principle of
      radiation protection ALARA and the doses that children receive during some common
      radiological procedures is poor. There is need to ensure adequate training on
      radiation hazards and protection at all levels of medical education.

PMID- 24887250
TI  - Awareness and attitudes to noise and its hazards in motor parks in a sub-urban
      Nigerian town.
AB  - AIMS AND OBJECTIVES: The study assessed awareness and attitudes of people working
      in the environment (users) of the motor parks (but not travelers), in a sub-urban
      town to environmental noise and its hazards. SUBJECTS AND METHODS: Regular users
      of major motor parks in Sagamu were administered with pretested structured
      questionnaire to obtain information on their awareness and attitudes concerning
      noise and NIHL at the parks. Descriptive and comparative analysis of the data
      obtained was performed by using SPSS version 15.0. RESULTS: Data from 387
      subjects were analysed; 61.2% were males, mean age was 35.5 11.4 years, 56.8% had
      secondary school education, and 50.6% were vehicle drivers or conductors. 51.2%
      ascribed vehicular traffic the major source of noise generation at the parks,
      while average noise level was 84.1 +/- 6.0 dBA. Among the subjects, 61.2%
      approved motor park was noisy, 47.8% (185/387) were aware of NIHL. Awareness did
      not change with age and sex, but increased significantly with level of education.
      51.9% were concerned about the noisy environment, 12.7% (49/387) protected
      themselves from the effect of the noise, 6.1% used ear plugs. Attitudes of the
      users did not change with age, sex, and level of education. CONCLUSIONS: Noise
      level at the motor parks were marginally high, awareness of the users to noise
      and its hazards was relatively high but attitudes concerning protection from
      noise hazards was poor. Health education for the users and noise regulation at
      the parks were recommended.

PMID- 24887251
TI  - Laparoscopic pyeloplasty for children with pelvic ureteric junction obstruction:
      an institutional experience.
AB  - AIMS AND OBJECTIVES: To give a report of 36 consecutive children who underwent
      laparoscopic Anderson-Hynes dismembered pyeloplasty by a single lead surgeon.
      PATIENTS AND METHODS: The diagnosis of pelviureteric junction obstruction was
      firmly established in all patients based on history, clinical examination, renal
      sonography and scintigraphy. Transperitoneal laparoscopic Anderson-Hynes
      pyeloplasty was performed in all the patients. Age at surgery, duration of
      operation, complications and outcome were documented. Children were followed up
      for symptoms, and diuretics renography was repeated at 3 months. RESULTS: A total
      of 36 children 5 months to 11 years (25 boys and 11 girls) under- went
      laparoscopic Anderson- Hynes pyeloplasty over a 4- year period. Mean age at
      surgery was 41 months (range 7 to 144). Seventeen (47%) cases were antenatally
      diagnosed. The mean operating time was 247 min. No patient required blood
      transfusion, and there were no intra-operative complications. The mean
      postoperative hospital stay was 5.8 days. There were 7 postoperative
      complications including urinary tract infection (n=6) and shoulder pain (n=1).
      The symptoms improved in 32(89%) children. There were 3 conversions, 2 due to non
      rotated kidney and one due to double right moiety. One child had failed
      pyeloplasty with deteriorating renal function. He had a redo open pyeloplasty.
      The mean split renal function before surgery and at follow up diuretic scan was
      36.2 vs 42.1, P=0.001. The mean follow up period was 30 months. CONCLUSION:
      Laparoscopic Anderson-Hynes pyeloplasty is safe and effective in the management
      of children with pelvi-ureteric junction obstruction.

PMID- 24887253
TI  - The relationship between obesity and peripheral arterial disease in adult
      Nigerian diabetics.
AB  - AIMS AND OBJECTIVES: The aim was to identify any relationship between obesity and
      peripheral arterial disease (PAD) in diabetic subjects. SUBJECTS AND METHODS:
      Male and female diabetic subjects aged 50-89 years. Body mass index (BMI) was
      used to estimate total body weight and the waist-to- hip ratio (WHR) as well as
      waist circumference (WC) were used for abdominal fat distribution estimation.
      Peripheral arterial disease was defined by an ankle brachial index <0.9. RESULTS:
      Peripheral arterial disease (PAD) was observed in 52.5% of the subjects. BMI, WHR
      and WC did not correlate with PAD. CONCLUSION: None of the parameters (i.e BMI,
      WHR and WC) used to assess the relationship between obesity and PAD was found to
      correlate with PAD.

PMID- 24887252
TI  - A comparative study between caudal bupivacaine and bupivacaine co-administered
      with neostigmine for postoperative analgesia in children.
AB  - AIMS AND OBJECTIVES: The aim of this study was to compare the duration of
      postoperative analgesia and possible adverse effects produced by caudal
      bupivacaine 0.25% at 1 ml/kg with or without 1.5 ug/kg of neostigmine in children
      undergoing unilateral herniotomy. PATIENTS AND METHODS: Sixty-six children aged 1
      6 years, of ASA physical status classes I or II for elective unilateral
      herniotomy under general anaesthesia without premedication were studied. The
      patients were randomly allocated into two groups of 33 each. Group B received
      caudal analgesia with plain bupivacaine 0.25% at 1 ml/kg alone, while group BN
      received caudal analgesia using a mixture of plain bupivacaine 0.25% at 1 ml/kg
      and neostigmine 1.5 ug/ kg. Postoperatively, monitoring of pain scores and time
      to first analgesic request and, total dose of analgesics administered in the
      first 24 hours were recorded. RESULTS: All the patients participated throughout
      the study. There were no differences in the demographic characteristics (age,
      weight, ASA status)between the two groups. The mean duration of effective
      analgesia was significantly longer in group BN, 460 +/- 60.2 min. compared to
      group B, 286.4 +/- 47.8 mins, (p < 0.001). The analgesic requirement within the
      first 24 hours postoperatively was also significantly reduced in group BN, p <
      0.001. CONCLUSION: The study shows that the addition of low dose neostigmine to
      caudal isobaric bupivacaine significantly prolonged the time to first analgesic
      request and hence significantly reduced postoperative analgesic requirement.

PMID- 24887254
TI  - Outcome of surgery for upper cervical spine injuries in Nigerians.
AB  - AIMS AND OBJECTIVES: . This is a review of the initial experience with surgical
      management of upper cervical spine injuries. MATERIALS AND METHODS: The clinical
      case notes of patients surgically managed for UCSI were analysed for aetiology,
      presentation, duration of symptoms before presentation and surgery, pre- and post
      operative Frankel grading, nature of injury and type of surgery. RESULTS: Eleven
      male and one female patients (mean age; 41.8 years; range 22-58 years) with UCSI
      were managed surgically. All the patients were involved in road traffic crashes.
      The case distribution were odontoid peg fracture [type II] alone (2 cases),
      hangman fracture alone (5 cases), both C1/2 subluxation and odontoid peg fracture
      (4 cases) and complex C2 injury (1 case). The surgical management includes C1
      posterior ring excision and occipitocervical fusion [C0 - C4] (one patient),
      modified Gallie fusion alone (six patients), combined modified Gallie fusion and
      Rogers interspinous wiring (three patients). One patient each had C1/C2
      interspinous wiring and combined modified Gallie fusion and occipito-cervical
      fusion [C0 - C4]. Post-operatively, two patients improved from Frankel C to D, 2
      patients from C to E and one patient from D to E. The other patients with Frankel
      D and E injuries pre-operatively remained in status quo post-operatively. Eleven
      of the patients were discharged home on progressive ambulation with one having
      neck stiffness and one patient died 7 weeks post- surgery. CONCLUSION: Odontoid
      peg and hangman fractures were the most common indications for upper cervical
      spine surgery for trauma in our unit, and the post- operative outcome appears
      satisfactory.

PMID- 24887255
TI  - Bone malignancies in orthopaedic hospital Igbobi Lagos, Nigeria.
AB  - AIMS AND OBJECTIVES: To document the pattern of bone malignancies in a highly
      populated orthopaedic hospital in Lagos Nigeria; PATIENTS AND METHODS: A total of
      21 cases of primary malignant bone tumours were studied. This comprised 12 cases
      of Osteosarcoma, 7 cases of Malignant Fibrous Histiocytoma (MFH) and 2 cases of
      Chondrosarcoma. Males (13) were affected more than females (8) giving a male to
      female ratio of 1.6 to 1. The age range was 7 to 45 years with a median age of 24
      years. The diameter of the swelling ranged from 6 to 20 cm with a median of 12
      cm. All patients had ablative surgery except for those with affectation of the
      ilium. Data was analysed using the Statistical Package for Social Sciences (SPSS
      16). Enneking's classification was used to grade the tumour. The duration of
      symptoms of all the patients before presentation ranged from 3 weeks to 4 years
      with a mean of 7 months. The commonest site affected was around the knee (76.2%);
      distal femur had 42.9% and proximal tibia 33.3%. RESULTS: Osteosarcoma was the
      most common malignant bone tumour in this series and accounted for 57.1%. The
      peak incidence was found in the 2nd decade of life. The youngest patient was 7
      years old and the oldest 43 years. The tumour was found primarily around the
      knee. 7 cases were in the distal part of the femur, 4 in the proximal part of the
      tibia and 1 case was found in the distal radius. Out of the 12 patients with
      osteosarcoma, 8 had paraosteal type (5 high grade, 3 intermediate grade), the
      remaining 4 had periosteal (all high grade) Malignant Fibrous Histiocytoma was
      found in 7 patients and accounted for 33.3%. The peak incidence was found in 3rd
      and 4th decades. 4 out of the 7 patients were high grade pleomorphic
      osteosarcoma, 2 were myxoid high grade dedifferentiated and one was low grade
      giant cell tumour type. Chondrosarcoma was found in 2 patients, accounting for
      9.5%. both cases were in the ilium CONCLUSION: Primary malignant bone tumours
      occurred in children and young adult in this study. It is commoner among males
      and most of the patients presented late to the hospital. Osteosarcoma is the
      commonest followed by Malignant Fibrous Histiocytoma, both occurred commonly
      around the knee and chondrosarcoma on the ilium.

PMID- 24887256
TI  - Mobile videoconferencing for enhanced emergency medical communication - a shot in
      the dark or a walk in the park? -- A simulation study.
AB  - BACKGROUND: Videoconferencing on mobile phones may enhance communication, but
      knowledge on its quality in various situations is needed before it can be used in
      medical emergencies. Mobile phones automatically activate loudspeaker
      functionality during videoconferencing, making calls particularly vulnerable to
      background noise. The aim of this study was to investigate if videoconferencing
      can be used between lay bystanders and Emergency Medical Dispatch (EMD) operators
      for initial emergency calls during medical emergencies, under suboptimal sound
      and light conditions. METHODS: Videoconferencing was tested between 90 volunteers
      and an emergency medical dispatcher in a standardized scenario of a medical
      emergency. Three different environments were used for the trials: indoors with
      moderate background noise, outdoors with daylight and much background noise, and
      outdoors during nighttime with little background noise. Thirty participants were
      recruited for each of the three locations. After informed consent, each
      participant was asked to use a video mobile phone to communicate with an EMD
      operator. During the video call the EMD operator gave instructions for tasks to
      be performed by the participant. The video quality from the caller to the EMD was
      evaluated by the EMD operator and rated on a five step scale ranging from "not
      able to see" to "good video quality". Sound quality between participants and EMD
      operators was assessed by a method developed for this trial. Kruskal - Wallis and
      Chi-square tests were used for statistical analysis. RESULTS: Video quality was
      significantly different between the groups (p <0.001), and the nighttime group
      had lower video quality. For most sessions in the nighttime group it was still
      possible to see actions done at the simulated emergency site. All participants
      were able to perform their tasks according to the instructions given by
      dispatchers, although with a need for more repetitions during sessions with much
      background noise. No calls were rated by dispatchers as incomprehensible due to
      low sound quality and only 3% of the calls were considered somewhat difficult or
      very difficult to understand. CONCLUSIONS: Videoconferencing on mobile phones can
      be used for the initial emergency call during medical emergencies also in
      suboptimal conditions.

PMID- 24887258
TI  - Whose responsibility is it to make life worth living?

PMID- 24887257
TI  - Image-based medical expert teleconsultation in acute care of injuries. A
      systematic review of effects on information accuracy, diagnostic validity,
      clinical outcome, and user satisfaction.
AB  - OBJECTIVE: To systematically review the literature on image-based telemedicine
      for medical expert consultation in acute care of injuries, considering system,
      user, and clinical aspects. DESIGN: Systematic review of peer-reviewed journal
      articles. DATA SOURCES: Searches of five databases and in eligible articles,
      relevant reviews, and specialized peer-reviewed journals. ELIGIBILITY CRITERIA:
      Studies were included that covered teleconsultation systems based on image
      capture and transfer with the objective of seeking medical expertise for the
      diagnostic and treatment of acute injury care and that presented the evaluation
      of one or several aspects of the system based on empirical data. Studies of
      systems not under routine practice or including real-time interactive video
      conferencing were excluded. METHOD: The procedures used in this review followed
      the PRISMA Statement. Predefined criteria were used for the assessment of the
      risk of bias. The DeLone and McLean Information System Success Model was used as
      a framework to synthesise the results according to system quality, user
      satisfaction, information quality and net benefits. All data extractions were
      done by at least two reviewers independently. RESULTS: Out of 331 articles, 24
      were found eligible. Diagnostic validity and management outcomes were often
      studied; fewer studies focused on system quality and user satisfaction. Most
      systems were evaluated at a feasibility stage or during small-scale pilot
      testing. Although the results of the evaluations were generally positive, biases
      in the methodology of evaluation were concerning selection, performance and
      exclusion. Gold standards and statistical tests were not always used when
      assessing diagnostic validity and patient management. CONCLUSIONS: Image-based
      telemedicine systems for injury emergency care tend to support valid diagnosis
      and influence patient management. The evidence relates to a few clinical fields,
      and has substantial methodological shortcomings. As in the case of telemedicine
      in general, user and system quality aspects are poorly documented, both of which
      affect scale up of such programs.

PMID- 24887259
TI  - Antidiabetic potential of polyoxotungstates: in vitro and in vivo studies.
AB  - Diabetes mellitus is a chronic metabolic disorder continuously affecting people
      all over the world. A common way to treat diabetes mellitus is to limit the
      conversion of carbohydrates into glucose which is mediated by glucosidase
      enzymes. Diabetes mellitus is also famous for its life-threatening microvascular
      (retinopathy, neuropathy and nephropathy) and macrovascular (atherosclerosis)
      complications. Aldose reductases present in eye lens (ALR1) and kidney (ALR2) are
      responsible for microvascular complications. The production of advanced glycation
      end products (AGEs) is involved in the development of atherosclerosis. The
      present work was aimed at the synthesis and in vitro/in vivo evaluation of
      different polyoxotungstates against glucosidases (alpha- and beta), aldose
      reductases (ALR1 and ALR2) and AGEs to discover a new treatment which may limit
      the complications associated with diabetes mellitus. The polyanion [P6W18O79](20
      ) was found to be the most potent inhibitor of alpha-glucosidase (IC50 = 1.33 +/-
      0.41 MUM), ALR1 (IC50 = 0.4 +/- 0.009 MUM) and ALR2 (IC50 = 0.38 +/- 0.02 MUM).
      Animal studies showed that the polyanion [H2W12O40](6-) was very effective in
      reducing the blood glucose level to 84.25 +/- 5.07 mg dL(-1) when compared with
      standard antidiabetic drug glibenclamide (150.62 +/- 9.35 mg dL(-1)) measured
      after maximum 8 h of dose administration. The data obtained from in vitro and in
      vivo experiments confirm that [P6W18O79](20-) and [H2W12O40](6-) could be used as
      a new treatment of diabetes mellitus. 

PMID- 24887260
TI  - Clinical mentorship of nurse initiated antiretroviral therapy in Khayelitsha,
      South Africa: a quality of care assessment.
AB  - INTRODUCTION: To combat the AIDS epidemic and increase HIV treatment access, the
      South African government implemented a nurse-based, doctor-supported model of
      care that decentralizes administration of antiretroviral treatment (ART) for HIV
      positive patients through nurse initiated and managed ART. Medecins Sans
      Frontieres (MSF) implemented a mentorship programme to ensure successful task
      shifting, subsequently assessing the quality of clinical care provided by nurses.
      METHODS: A before-after cross-sectional study was conducted on nurses completing
      the mentorship programme in Khayelitsha, South Africa, from February 2011
      September 2012. Routine clinical data from 229 patient folders and 21 self
      assessment questionnaires was collected to determine the number of patients
      initiated on ART by nurses; quality of ART management before-after mentorship;
      patient characteristics for doctor and nurse ART initiations; and nurse self
      assessments after mentorship. RESULTS: Twenty one nurses were authorized by one
      nurse mentor with one part-time medical officer's support, resulting in nurses
      initiating 77% of ART eligible patients. Improvements in ART management were
      found for drawing required bloods (91% vs 99%, p = 0.03), assessing adherence
      (50% vs 78%, p<0.001) and WHO staging (63% vs 91%, p<0.001). Nurse ART initiation
      indicators were successfully completed at 95-100% for 11 of 16 indicators:
      clinical presentation; patient weight; baseline blood work (CD4, creatinine,
      haemoglobin); STI screening; WHO stage, correlating medical history; medications
      prescribed appropriately; ART start date; and documented return date. Doctors
      initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease
      than nurses. Nurse confidence improved for managing HIV-infected children and
      pregnant women, blood result interpretation and long-term side effects.
      CONCLUSIONS: Implementation of a clinical mentorship programme in Khayelitsha led
      to nurse initiation of a majority of eligible patients, enabling medical officers
      to manage complex cases. As mentorship can increase clinical confidence and
      enhance professional development, it should be considered essential for universal
      ART access in resource limited settings.

PMID- 24887261
TI  - Validation of phenol red versus gravimetric method for water reabsorption
      correction and study of gender differences in Doluisio's absorption technique.
AB  - The aim of the present study was to develop a method for water flux reabsorption
      measurement in Doluisio's Perfusion Technique based on the use of phenol red as a
      non-absorbable marker and to validate it by comparison with gravimetric
      procedure. The compounds selected for the study were metoprolol, atenolol,
      cimetidine and cefadroxil in order to include low, intermediate and high
      permeability drugs absorbed by passive diffusion and by carrier mediated
      mechanism. The intestinal permeabilities (Peff) of the drugs were obtained in
      male and female Wistar rats and calculated using both methods of water flux
      correction. The absorption rate coefficients of all the assayed compounds did not
      show statistically significant differences between male and female rats
      consequently all the individual values were combined to compare between
      reabsorption methods. The absorption rate coefficients and permeability values
      did not show statistically significant differences between the two strategies of
      concentration correction. The apparent zero order water absorption coefficients
      were also similar in both correction procedures. In conclusion gravimetric and
      phenol red method for water reabsorption correction are accurate and
      interchangeable for permeability estimation in closed loop perfusion method. 

PMID- 24887263
TI  - Seroprevalence of Toxoplasma gondii in the Iranian general population: a
      systematic review and meta-analysis.
AB  - Toxoplasma gondii is one of the most common protozoan parasites with widespread
      distribution globally. It is the causative agent of Toxoplasma infection, which
      is prevalent in human and other warm-blooded vertebrates. While T. gondii
      infection in healthy people is usually asymptomatic, it can lead to serious
      pathological effects in congenital cases and immunodeficient patients. We sought
      to identify the seroprevalence rate of Toxoplasma infection in the Iranian
      general population to develop a comprehensive description of the disease
      condition in Iran for future use. Electronic databases (PubMed, Google Scholar,
      Science Direct, and Scopus) and Persian language databases (Magiran, Scientific
      Information Database [SID], Iran Medex, and Iran Doc) were searched. Furthermore,
      graduate student dissertations and proceedings of national parasitology
      congresses were searched manually. Our search resulted in a total of 35 reports
      published from 1978 to 2012.These include 22 published articles, 1 unpublished
      study, 8 proceedings from the Iranian conference of parasitology, and 4 graduate
      student dissertations, resulting in 52,294 individuals and 23,385 IgG
      seropositive cases. The random errors method was used for this meta-analysis. The
      result shows that the overall seroprevalence rate of toxoplasmos is among the
      general population in Iran was 39.3% (95% CI=33.0%-45.7%). There was no
      significant difference in the seroprevalence rate between male and female
      patients. A significant linear trend of increasing overall prevalence by age was
      noted (P<0.0001). In addition, the data indicates that there are high
      seroprevalence in groups who have direct contact with cats, consume uncooked meat
      and raw fruits or vegetables, in farmers and Housewife, individuals who have a
      low level of education, and live in rural areas. To the best of our knowledge,
      this is the first systematic review of T. gondii infection seroprevalence in
      Iran, which shows a high prevalence of Toxoplasma infection (more than one
      third). We highly recommend further study for the purposes of aiding patient
      management and developing more efficient diagnostic tests and effective
      prevention approaches. 

PMID- 24887262
TI  - Hepatic arterial embolization in patients with neuroendocrine tumors.
AB  - Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms
      (NENs). Presence and extension of liver metastases are considered important
      prognostic factors, as they may significantly impair the patient's quality of
      life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN
      liver metastases include surgical resection, liver transplantation, chemotherapy
      and biotherapy. Surgery is the gold standard for curative therapy, but in most of
      NEN patients with liver metastases, when surgery can not be applied, minimally
      invasive therapeutic approaches are adopted. They include trans-arterial
      embolization (TAE), trans-arterial chemoembolization (TACE), radiofrequency
      thermal ablation and new emerging techniques.TAE is based on selective infusion
      of particles in the branch of the hepatic artery supplying the tumor lesions. The
      goal of TAE is to occlude tumor blood vessels resulting in ischemia and necrosis.
      Many reports have shown that TAE can reduce tumor size and hormone output,
      resulting in palliation of symptoms without the use of cytotoxic drugs, resulting
      in better tolerability. This review will focus on TAE performance and safety in
      NEN patients with liver metastases. 

PMID- 24887264
TI  - The formation of tau pore-like structures is prevalent and cell specific:
      possible implications for the disease phenotypes.
AB  - Pathological aggregation of the microtubule-associated protein tau and subsequent
      accumulation of neurofibrillary tangles (NFTs) or other tau-containing inclusions
      are defining histopathological features of many neurodegenerative diseases, which
      are collectively known as tauopathies. Due to conflicting results regarding a
      correlation between the presence of NFTs and disease progression, the mechanism
      linking pathological tau aggregation with cell death is poorly understood. An
      emerging view is that NFTs are not the toxic entity in tauopathies; rather, tau
      intermediates between monomers and NFTs are pathogenic. Several proteins
      associated with neurodegenerative diseases, such as beta-amyloid (Abeta) and
      alpha-synuclein, have the tendency to form pore-like amyloid structures (annular
      protofibrils, APFs) that mimic the membrane-disrupting properties of pore-forming
      protein toxins. The present study examined the similarities of tau APFs with
      other tau amyloid species and showed for the first time the presence of tau APFs
      in brain tissue from patients with progressive supranuclear palsy (PSP) and
      dementia with Lewy bodies (DLB), as well as in the P301L mouse model, which
      overexpresses mutated tau. Furthermore, we found that APFs are preceded by tau
      oligomers and do not go on to form NFTs, evading fibrillar fate. Collectively,
      our results demonstrate that in vivo APF formation depends on mutations in tau,
      phosphorylation levels, and cell type. These findings establish the pathological
      significance of tau APFs in vivo and highlight their suitability as therapeutic
      targets for several neurodegenerative tauopathies.

PMID- 24887267
TI  - Sticks and stones.

PMID- 24887265
TI  - Chromatin CKAP2, a new proliferation marker, as independent prognostic indicator
      in breast cancer.
AB  - BACKGROUND: The level of proliferation activity is a strong prognostic or
      predictive indicator in breast cancer, but its optimal measurement is still in
      debate, necessitating new proliferation markers. In the present study, the
      prognostic significance of the CKAP2-positive cell count (CPCC), a new
      proliferation marker, was evaluated, and the results were compared with those for
      the mitotic activity index (MAI). METHODS: This study included 375 early-stage
      breast cancer samples collected from two institutions between 2000 and 2006.
      Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox
      proportional hazard regression models were fitted to determine the association
      between the CPCC and relapse-free survival (RFS) amongst three groups formed on
      the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest
      values, respectively, and group 1 the lowest. RESULTS: After adjustment for age,
      T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor
      status, institution, and year of surgical resection, the CPCC was associated with
      a significantly worse RFS {hazard ratio [HR]  = 4.10 (95% CI: 1.64-10.29) for
      group 2; HR  = 4.35 (95% CI: 2.04-10.35) for group 3}. Moreover, its prognostic
      significance was similar to or higher than that based on the MAI {HR  = 2.05 (95%
      CI: 0.94-4.65) for group 2; HR  = 2.35 (95% CI: 1.09-5.10) for group 3}. In
      subgroup analyses, the CPCC showed a prognostic significance in the luminal A and
      triple-negative subgroups, but not in the HER2-positive subgroup. CONCLUSIONS:
      Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast
      cancer, and could potentially replace the MAI in clinical evaluation of
      proliferation activity. Additionally, our study results suggest that the
      prognostic significance of proliferation activity differs among the various
      subgroups of breast cancer.

PMID- 24887269
TI  - Does early ambulation increase the risk of pulmonary embolism in deep vein
      thrombosis? A review of the literature.
AB  - Therapeutic measures targeting deep vein thrombosis (DVT) are often aggressive to
      prevent pulmonary embolism (PE). Once receiving anticoagulation therapy, however,
      there are different viewpoints on whether patients should remain sedentary or be
      allowed to ambulate, particularly in the home setting. The current literature was
      reviewed in a systematic fashion to ascertain the risks and benefits of activity
      level in patients with DVT with regard to PE formation. All studies uniformly
      demonstrated at least no significant differences in PE formation with either
      activity level in these DVT patients. There is no evidence to suggest that
      ambulation by anticoagulated DVT patients in the home setting increases the risk
      of PE development. 

PMID- 24887266
TI  - Efficacy and safety of mesenchymal stromal cells in preclinical models of acute
      lung injury: a systematic review protocol.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) in humans is caused by an
      unchecked proinflammatory response that results in diffuse and severe lung
      injury, and it is associated with a mortality rate of 35 to 45%. Mesenchymal
      stromal cells (MSCs; 'adult stem cells') could represent a promising new therapy
      for this syndrome, since preclinical evidence suggests that MSCs may ameliorate
      lung injury. Prior to a human clinical trial, our aim is to conduct a systematic
      review to compare the efficacy and safety of MSC therapy versus controls in
      preclinical models of acute lung injury that mimic some aspects of the human
      ARDS. METHODS/DESIGN: We will include comparative preclinical studies (randomized
      and non-randomized) of acute lung injury in which MSCs were administered and
      outcomes compared to animals given a vehicle control. The primary outcome will be
      death. Secondary outcomes will include the four key features of preclinical acute
      lung injury as defined by the American Thoracic Society consensus conference
      (histologic evidence of lung injury, altered alveolar capillary barrier, lung
      inflammatory response, and physiological dysfunction) and pathogen clearance for
      acute lung injury models that are caused by infection. Electronic searches of
      MEDLINE, Embase, BIOSIS Previews, and Web of Science will be constructed and
      reviewed by the Peer Review of Electronic Search Strategies (PRESS) process.
      Search results will be screened independently and in duplicate. Data from
      eligible studies will be extracted, pooled, and analyzed using random effects
      models. Risk of bias will be assessed using the Cochrane risk of bias tool, and
      individual study reporting will be assessed according to the Animal Research:
      Reporting of In Vivo Experiments (ARRIVE) guidelines. DISCUSSION: The results of
      this systematic review will comprehensively summarize the safety and efficacy of
      MSC therapy in preclinical models of acute lung injury. Our results will help
      translational scientists and clinical trialists to determine whether sufficient
      evidence exists to perform a human clinical trial. These results may also guide
      future acute lung injury preclinical and clinical research.

PMID- 24887270
TI  - The Food and Drug Administration's initiative for safe design and effective use
      of home medical equipment.
AB  - Although home-use medical devices provide significant benefits, including
      improved quality of life and cost savings, they are associated with unique risks.
      These risks result from interactions among the user, the use environment, and the
      device, and they can greatly impact user and patient safety. This article
      describes measures being taken by the Food and Drug Administration to address
      safe use of medical equipment by trained and untrained people outside of clinical
      facilities. 

PMID- 24887271
TI  - The role of the speech-language pathologist in home care.
AB  - Speech language pathologists play an important role in the care of patients with
      speech, language, or swallowing difficulties that can result from a variety of
      medical conditions. This article describes how speech language pathologists
      assess and treat these conditions and the red flags that suggest a referral to a
      speech language pathologist is indicated. 

PMID- 24887272
TI  - Poor air quality in homes of Medicare recipients with diabetes.
AB  - Poor air quality has been associated with chronic illness such as diabetes. This
      can be of particular importance for older adults with diabetes and other chronic
      conditions who spend most of their time indoors. The purpose of this study was to
      assess home air quality and residents' awareness and concerns about air quality
      in rural underserved areas of upstate New York. Implications for home care
      clinicians are discussed. 

PMID- 24887275
TI  - Insulin.

PMID- 24887273
TI  - Diabetes, depression, and OASIS-C: a guide for home healthcare clinicians.
AB  - Depression is significantly higher among elderly adults receiving home
      healthcare, particularly among adults with Type 2 diabetes. Depression leads to
      greater medical illness, functional impairment, and chronic pain. Opportunities
      are often missed to improve mental health and general medical outcomes when
      mental illness is underrecognized and undertreated. This article discusses the
      mandate by the Centers for Medicare & Medicaid Services (CMS), Outcome and
      Assessment Information Set-C (OASIS-C) (2009) for the use of the Patient Health
      Questionnaire (PHQ-2) to screen for depression in home care patients, with
      special emphasis on the patient with diabetes. 

PMID- 24887276
TI  - Hepatitis C.

PMID- 24887277
TI  - Indwelling bladder catheterization.

PMID- 24887278
TI  - Norma Nichols, Arbor Hospice music therapist.

PMID- 24887279
TI  - Moving to a value-based world: what is home care going to need to do to thrive?

PMID- 24887280
TI  - It takes a team.

PMID- 24887281
TI  - Global metabolite profiling of synovial fluid for the specific diagnosis of
      rheumatoid arthritis from other inflammatory arthritis.
AB  - Currently, reliable biomarkers that can be used to distinguish rheumatoid
      arthritis (RA) from other inflammatory diseases are unavailable. To find possible
      distinctive metabolic patterns and biomarker candidates for RA, we performed
      global metabolite profiling of synovial fluid samples. Synovial fluid samples
      from 38 patients with RA, ankylosing spondylitis, Behcet's disease, and gout were
      analyzed by gas chromatography/time-of-flight mass spectrometry (GC/TOF MS).
      Orthogonal partial least-squares discriminant and hierarchical clustering
      analyses were performed for the discrimination of RA and non-RA groups. Variable
      importance for projection values were determined, and the Wilcoxon-Mann-Whitney
      test and the breakdown and one-way analysis of variance were conducted to
      identify potential biomarkers for RA. A total of 105 metabolites were identified
      from synovial fluid samples. The score plot of orthogonal partial least squares
      discriminant analysis showed significant discrimination between the RA and non-RA
      groups. The 20 metabolites, including citrulline, succinate, glutamine,
      octadecanol, isopalmitic acid, and glycerol, were identified as potential
      biomarkers for RA. These metabolites were found to be associated with the urea
      and TCA cycles as well as fatty acid and amino acid metabolism. The metabolomic
      analysis results demonstrated that global metabolite profiling by GC/TOF MS might
      be a useful tool for the effective diagnosis and further understanding of RA. 

PMID- 24887282
TI  - A neutralizing recombinant single chain antibody, scFv, against BaP1, A P-I
      hemorrhagic metalloproteinase from Bothrops asper snake venom.
AB  - BaP1 is a P-I class snake venom metalloproteinase (SVMP) relevant in the local
      tissue damage associated with envenomings by Bothrops asper, a medically
      important snake species in Central America and parts of South and North America.
      The main treatment for these accidents is the passive immunotherapy using
      antibodies raised in horses. In order to obtain more specific and batch-to-batch
      consistent antivenons, recombinant antibodies are considered a good option
      compared to animal immunization. We constructed a recombinant single chain
      variable fragment (scFv) from a monoclonal antibody against BaP1 (MABaP1)
      formerly secreted by a hybridoma clone. This recombinant antibody was cloned into
      pMST3 vector in fusion with SUMO protein and contains VH and VL domains linked by
      a flexible (G4S)3 polypeptide (scFvBaP1). The aim of this work was to produce
      scFvBaP1 and to evaluate its potential concerning the neutralization of
      biologically important activities of BaP1. The cytoplasmic expression of this
      construct was successfully achieved in C43 (DE3) bacteria. Our results showed
      that scFvBaP1-SUMO fusion protein presented an electrophoretic band of around 43
      kDa from which SUMO alone corresponded to 13.6 kDa, and only the scFv was able to
      recognize BaP1 as well as the whole venom by ELISA. In contrast, neither an
      irrelevant scFv anti-LDL nor its MoAb partner recognized it. BaP1-induced
      fibrinolysis was significantly neutralized by scFvBaP1, but not by SUMO, in a
      concentration-dependent manner. In addition, scFvBaP1, as well as MaBaP1,
      completely neutralized in vivo hemorrhage, muscle necrosis, and inflammation
      induced by the toxin. Docking analyses revealed possible modes of interaction of
      the recombinant antibody with BaP1. Our data showed that scFv recognized BaP1 and
      whole B. asper venom, and neutralized biological effects of this SVMP. This scFv
      antibody can be used for understanding the molecular mechanisms of neutralization
      of SVMPs, and for exploring the potential of recombinant antibody fragments for
      improving the neutralization of local tissue damage in snakebite envenoming. 

PMID- 24887283
TI  - In vitro labelling of muscle type nicotinic receptors using a fluorophore
      conjugated pinnatoxin F derivative.
AB  - Fluorescent molecules are regularly utilised to study ligand-receptor
      interactions. Many ligands for nicotinic receptors have been conjugated with
      fluorophores to study receptor kinetics, recycling and ligand binding
      characteristics. These include small agonist molecules, as well as large peptidic
      antagonists. However, no small molecule antagonists have been investigated using
      this method. Pinnatoxin F is a newly discovered non-peptidic muscle type
      nicotinic receptor antagonist produced by the marine dinoflagellate species
      Vulcanodinium rugosum. This molecule has the potential for conjugation to a
      fluorophore, allowing subsequent visualisation of interactions with nicotinic
      receptors. Pinnatoxin F was modified by addition of diaminopolyether spacers, to
      which a fluorophore (VivoTag((r)) 645) was conjugated. The fluorescent pinnatoxin
      was then applied to muscle sections from thy1-YFP-H transgenic mice, which
      express YFP in motor nerves, to allow direct visualization of fluorescent binding
      at the neuromuscular junction. The addition of both the diaminopolyether spacer
      and the VivoTag((r)) 645 reduced the potency of pinnatoxin F, as evidenced by a
      reduction in in vitro neuromuscular blocking activity and in vivo toxicity.
      Despite this reduced potency, the fluorescent molecule selectively labelled
      endplate regions in thy1-YFP mouse muscle sections and this labelling was
      inhibited by pre-exposure of muscle sections to native pinnatoxin F or the
      nicotinic antagonist alpha-bungarotoxin. This study proves nicotinic receptor
      binding activity of pinnatoxin F and is the first example of a fluorophore
      conjugated small-molecule antagonist for nicotinic receptors. These results
      indicate the potential for other small-molecule nicotinic receptor antagonists to
      be fluorescently labelled and used as probes for specific nicotinic receptor
      subtypes. 

PMID- 24887284
TI  - The effects of varying poly(ethylene glycol) hydrogel crosslinking density and
      the crosslinking mechanism on protein accumulation in three-dimensional
      hydrogels.
AB  - Matrix stiffness has been shown to play an important role in modulating various
      cell fate processes such as differentiation and cell cycle. Given that the
      stiffness can be easily tuned by varying the crosslinking density, poly(ethylene
      glycol) (PEG) hydrogels have been widely used as an artificial cell niche.
      However, little is known about how changes in the hydrogel crosslinking density
      may affect the accumulation of exogenous growth factors within 3-D hydrogel
      scaffolds formed by different crosslinking mechanisms. To address such
      shortcomings, we measured protein diffusivity and accumulation within PEG
      hydrogels with varying PEG molecular weight, concentration and crosslinking
      mechanism. We found that protein accumulation increased substantially above a
      critical mesh size, which was distinct from the protein diffusivity trend,
      highlighting the importance of using protein accumulation as a parameter to
      better predict the cell fates in addition to protein diffusivity, a parameter
      commonly reported by researchers studying protein diffusion in hydrogels.
      Furthermore, we found that chain-growth-polymerized gels allowed more protein
      accumulation than step-growth-polymerized gels, which may be the result of
      network heterogeneity. The strategy used here can help quantify the effects of
      varying the hydrogel crosslinking density and crosslinking mechanism on protein
      diffusion in different types of hydrogel. Such tools could be broadly useful for
      interpreting cellular responses in hydrogels of varying stiffness for various
      tissue engineering applications. 

PMID- 24887285
TI  - Urease-induced calcification of segmented polymer hydrogels - a step towards
      artificial biomineralization.
AB  - Natural organic/inorganic composites, such as nacre, bones and teeth, are
      perfectly designed materials with exceptional mechanical properties. Numerous
      approaches have been taken to synthetically prepare such composites. The
      presented work describes a new way of mineralizing bulk materials on a large
      scale following the approach of bioinduced mineralization. To this end, a series
      of polymer conetworks with entrapped urease were prepared. After polymerization,
      the entrapped urease shows high enzymatic activity. The bioactive polymer
      conetworks were then treated with an aqueous mixture of urea and CaCl2. The
      urease-induced calcification indeed allows formation of carbonate crystals
      exclusively within the hydrogel even at room temperature. The influence of
      network composition, degree of cross-linking, immobilized urease concentration
      and temperature of calcification were investigated. By varying these parameters,
      spherical, monolithic clusters, as well as bar-like nanocrystals with different
      aspect ratios in spherical or dendritic arrays, are formed. The grown
      nanocrystals improve the stiffness of the starting material by up to 700-fold,
      provided that the microstructure shows a dense construction without pores and
      strong interaction between crystals and network. The process has the potential to
      generate a new class of hybrid materials that would be available on the
      macroscopic scale for use in lightweight design and medicine. 

PMID- 24887288
TI  - Stereoelectroencephalography in children and adolescents with difficult-to
      localize refractory focal epilepsy.
AB  - BACKGROUND: Although stereoelectroencephalography (SEEG) has been shown to be a
      valuable tool for preoperative decision making in focal epilepsy, there are few
      reports addressing the utility and safety of SEEG methodology applied to children
      and adolescents. OBJECTIVE: To present the results of our early experience using
      SEEG in pediatric patients with difficult-to-localize epilepsy who were not
      considered candidates for subdural grid evaluation. METHODS: Thirty children and
      adolescents with the diagnosis of medically refractory focal epilepsy (not
      considered ideal candidates for subdural grids and strip placement) underwent
      SEEG implantation. Demographics, electrophysiological localization of the
      hypothetical epileptogenic zone, complications, and seizure outcome after
      resections were analyzed. RESULTS: Eighteen patients (60%) underwent resections
      after SEEG implantations. In patients who did not undergo resections (12
      patients), reasons included failure to localize the epileptogenic zone (4
      patients); multifocal epileptogenic zone (4 patients); epileptogenic zone located
      in eloquent cortex, preventing resection (3 patients); and improvement in
      seizures after the implantation (1 patient). In patients who subsequently
      underwent resections, 10 patients (55.5%) were seizure free (Engel class I) and 5
      patients (27.7%) experienced seizure improvement (Engel class II or III) at the
      end of the follow-up period (mean, 25.9 months; range, 12 to 47 months). The
      complication rate in SEEG implantations was 3%. CONCLUSION: The SEEG methodology
      is safe and should be considered in children/adolescents with difficult-to
      localize epilepsy. When applied to highly complex and difficult-to-localize
      pediatric patients, SEEG may provide an additional opportunity for seizure
      freedom in association with a low morbidity rate.

PMID- 24887287
TI  - Comparison of long-term outcomes associated with endovascular treatment vs
      surgical treatment among Medicare beneficiaries with unruptured intracranial
      aneurysms.
AB  - BACKGROUND: Long-term outcomes associated with endovascular and surgical
      treatments for unruptured intracranial aneurysms are not well studied to date.
      OBJECTIVE: To determine the 5-year risk of new intracranial hemorrhage, second
      procedure, and all-cause mortality in elderly patients with unruptured
      intracranial aneurysms who underwent either surgical or endovascular treatment.
      METHODS: The study cohort included a representative sample of fee-for-service
      Medicare beneficiaries aged >=65 years who underwent endovascular or surgical
      treatment for unruptured intracranial aneurysms with postprocedure follow-up of
      4.7 (+/-3.0) years. Cox proportional hazards analysis was used to assess the
      relative risk (RR) of all-cause mortality, new intracranial hemorrhage, or second
      procedure for patients who underwent endovascular treatment compared with those
      who underwent surgical treatment after adjusting for potential confounders. The 5
      year survival was estimated for both treatment groups by using Kaplan-Meier
      survival methods. RESULTS: A total of 688 patients with unruptured intracranial
      aneurysms were treated with either endovascular (n = 398) or surgical treatment
      (n = 290). The rate of immediate postprocedural neurological complications (10.3%
      vs 3.5%, P = .001) was higher among patients treated with surgery than among
      those who underwent endovascular treatment. The estimated 5-year survival was
      92.8% and 94.8% in patients who underwent surgical and endovascular treatments,
      respectively. After adjusting for age, sex, and race/ethnicity, the RRs of all
      cause mortality (RR, 0.6; 95% confidence interval, 0.3-1.1) and new intracranial
      hemorrhage (RR, 0.4; 95% confidence interval, 0.2-0.8) were lower with
      endovascular treatment. CONCLUSION: In elderly patients with unruptured
      intracranial aneurysms, endovascular treatment was associated with lower rates of
      acute adverse events and long-term all-cause mortality and new intracranial
      hemorrhages.

PMID- 24887286
TI  - Exploration of bacterial community classes in major human habitats.
AB  - BACKGROUND: Determining bacterial abundance variation is the first step in
      understanding bacterial similarity between individuals. Categorization of
      bacterial communities into groups or community classes is the subsequent step in
      describing microbial distribution based on abundance patterns. Here, we present
      an analysis of the groupings of bacterial communities in stool, nasal, skin,
      vaginal and oral habitats in a healthy cohort of 236 subjects from the Human
      Microbiome Project. RESULTS: We identify distinct community group patterns in the
      anterior nares, four skin sites, and vagina at the genus level. We also confirm
      three enterotypes previously identified in stools. We identify two clusters with
      low silhouette values in most oral sites, in which bacterial communities are more
      homogeneous. Subjects sharing a community class in one habitat do not necessarily
      share a community class in another, except in the three vaginal sites and the
      symmetric habitats of the left and right retroauricular creases. Demographic
      factors, including gender, age, and ethnicity, significantly influence community
      composition in several habitats. Community classes in the vagina, retroauricular
      crease and stool are stable over approximately 200 days. CONCLUSION: The
      community composition, association of demographic factors with community classes,
      and demonstration of community stability deepen our understanding of the
      variability and dynamics of human microbiomes. This also has significant
      implications for experimental designs that seek microbial correlations with
      clinical phenotypes.

PMID- 24887290
TI  - A novel single twist-drill access device for multimodal intracranial monitoring:
      a 5-year single-institution experience.
AB  - BACKGROUND: Multimodal intracranial monitoring in the neurosurgical patient
      requires insertion of probes through multiple craniostomies. OBJECTIVE: To report
      our 5-year experience with a novel device allowing multimodal monitoring though a
      single twist-drill hole. METHODS: All devices (Hummingbird Synergy, Innerspace)
      were placed at the Kocher point between 2008 and 2013 at our institution. An
      independent clinical research nurse prospectively collected data on all bedside
      placements. Placement accuracy was graded on computed tomography scan as grade 1
      (ipsilateral frontal horn or third ventricle), grade 2 (contralateral lateral
      ventricle), and grade 3 (anywhere else). Infection was monitored with serial
      cerebrospinal fluid samples. RESULTS: Two hundred seventy-five devices (198 at
      bedside, 77 in operating room) were placed in patients with spontaneous
      subarachnoid hemorrhage (49%), traumatic brain injury (47%), and others (4%) for
      a median duration of 6 days. A junior (postgraduate year 1-2), midlevel
      (postgraduate year 3-4), or senior resident (postgraduate year 5-6) placed 39%,
      32%, and 29% of the devices, respectively. Ninety-two percent of all devices
      placed were draining cerebrospinal fluid, ie, were grade 1 (75%) or 2 (17%).
      Placement accuracy did not vary with level of training. Complications included
      hemorrhage (10%) and infection (4%), with 1 patient requiring intraparenchymal
      hematoma evacuation and a second requiring abscess drainage. These rates were
      lower than reported in the literature for standard external ventricular drains.
      CONCLUSION: Hummingbird Synergy is a novel single-port access device for
      multimodal intracranial monitoring that can be placed safely at the bedside or in
      the operating room with placement accuracy and has a complication profile similar
      to or better than that for standard external ventricular drains.

PMID- 24887289
TI  - Analysis of Mll1 deficiency identifies neurogenic transcriptional modules and
      Brn4 as a factor for direct astrocyte-to-neuron reprogramming.
AB  - BACKGROUND: Mixed lineage leukemia-1 (Mll1) epigenetically regulates gene
      expression patterns that specify cellular identity in both embryonic development
      and adult stem cell populations. In the adult mouse brain, multipotent neural
      stem cells (NSCs) in the subventricular zone generate new neurons throughout
      life, and Mll1 is required for this postnatal neurogenesis but not for glial cell
      differentiation. Analysis of Mll1-dependent transcription may identify neurogenic
      genes useful for the direct reprogramming of astrocytes into neurons. OBJECTIVE:
      To identify Mll1-dependent transcriptional modules and to determine whether genes
      in the neurogenic modules can be used to directly reprogram astrocytes into
      neurons. METHODS: We performed gene coexpression module analysis on microarray
      data from differentiating wild-type and Mll1-deleted subventricular zone NSCs.
      Key developmental regulators belonging to the neurogenic modules were
      overexpressed in Mll1-deleted cells and cultured cortical astrocytes, and cell
      phenotypes were analyzed by immunocytochemistry and electrophysiology. RESULTS:
      Transcriptional modules that correspond to neurogenesis were identified in wild
      type NSCs. Modules related to astrocytes and oligodendrocytes were enriched in
      Mll1-deleted NSCs, consistent with their gliogenic potential. Overexpression of
      genes selected from the neurogenic modules enhanced the production of neurons
      from Mll1-deleted cells, and overexpression of Brn4 (Pou3f4) in nonneurogenic
      cortical astroglia induced their transdifferentiation into electrophysiologically
      active neurons. CONCLUSION: Our results demonstrate that Mll1 is required for the
      expression of neurogenic but not gliogenic transcriptional modules in a
      multipotent NSC population and further indicate that specific Mll1-dependent
      genes may be useful for direct reprogramming strategies.

PMID- 24887291
TI  - Topographic changes in petrous bone anatomy in the presence of a vestibular
      schwannoma and implications for the retrosigmoid transmeatal approach.
AB  - BACKGROUND: The maneuver of transmeatal drilling carries the risk of injuring
      inner ear structures, which may cause immediate or delayed hearing loss.
      OBJECTIVE: To describe the changes in petrous bone anatomy caused by the tumor
      and to analyze both the incidence and the risk pattern for violation of the
      endolymphatic system in a surgical series. METHODS: One hundred patients operated
      on for vestibular schwannoma were included in this prospective study. Thin-slice
      computed tomography was performed before and after surgery. We assessed
      topographic measurements on both the pathological and healthy sides.
      Postoperatively, we evaluated anatomic and functional values. RESULTS: The
      diameter of the internal auditory canal was significantly larger (P < .001) in
      the petrous bones of the affected sides than in the contralateral healthy sides.
      An average of 5.6 +/- 1.8 mm of the internal auditory canal was drilled, and the
      distance from the medial border of the sigmoid sinus to the drilling line
      (tangential to the drilled surface of the posterior lip of the internal auditory
      canal) was 9.8 +/- 2.9 mm. A postoperative violation of the vestibular aqueduct
      (VA) was detected in 41 cases; the VA was intact in 55 cases; and the VA could
      not be clearly defined in 4 cases. The incidence of VA injury increased with
      increasing tumor size. In the patient group with good preoperative and
      postoperative hearing function, a VA injury occurred in 26% of cases, whereas the
      incidence increased to 67% in preoperatively deaf patients. CONCLUSION:
      Vestibular schwannomas cause significant distortion of the petrous bone anatomy.
      Detailed preoperative knowledge of the topography is necessary for the
      preservation of function.

PMID- 24887292
TI  - Clinical and surgical experience with the minipterional craniotomy.

PMID- 24887293
TI  - In reply: clinical and surgical experience with the minipterional craniotomy.

PMID- 24887294
TI  - Sex differences in acetylcholine-induced sweating responses due to physical
      training.
AB  - PURPOSE: The present study examined sex differences in the sweat gland response
      to acetylcholine (ACh) in physically trained and untrained male and female
      subjects. METHODS: Sweating responses were induced on the forearm and thigh in
      resting subjects by ACh iontophoresis using a 10% solution at 2 mA for 5 min at
      26 degrees C and 50% relative humidity. RESULTS: The ACh-induced sweating rate
      (SR) on the forearm and thigh was greater in physically trained male (P < 0.001
      for the forearm and thigh, respectively) and female (P = 0.08 for the forearm, P
      < 0.001 for the thigh) subjects than in untrained subjects of both sexes. The SR
      was also significantly greater in physically trained males compared to females at
      both sites (P < 0.001) and in untrained males compared to females on the thigh (P
      < 0.02) only, although the degree of difference was greater in trained subjects
      than in untrained subjects. These sex differences can be attributed to the
      difference in sweat output per gland rather than the number of activated sweat
      glands. CONCLUSION: We conclude that physical training enhances the ACh-induced
      SR in both sexes but that the degree of enhancement is greater in male than in
      female subjects. The effects of physical training and sex on the SR may be due to
      changes in peripheral sensitivity to ACh and/or sweat gland size.

PMID- 24887295
TI  - Zebrafish and conditioned place preference: a translational model of drug reward.
AB  - Addiction and substance abuse are found ubiquitously throughout human society. In
      the United States, these disorders are responsible for amassing hundreds of
      billions of dollars in annual costs associated with healthcare, crime and lost
      productivity. Efficacious treatments remain few in number, the development of
      which will be facilitated by comprehension of environmental, genetic,
      pharmacological and neurobiological mechanisms implicated in the pathogenesis of
      addiction. Animal models such as the zebrafish (Danio rerio) have gained momentum
      within various domains of translational research, and as a model of complex brain
      disorders (e.g., drug abuse). Behavioral quantification within the conditioned
      place preference (CPP) paradigm serves as a measure of the rewarding qualities of
      a given substance. If the animal develops an increase in preference for the drug
      paired environment, it is inferred that the drug has positive-reinforcing
      properties. This paper discusses the utility of the zebrafish model in
      conjunction with the CPP paradigm and reports CPP behavior following acute
      exposure to 0.0%, 0.25%, 0.50%, and 1.00% alcohol, and 0 mg/L, 50 mg/L, 100 mg/L
      and 150 mg/L caffeine.

PMID- 24887296
TI  - A Pre-Clinical Framework for Neural Control of a Therapeutic Upper-Limb
      Exoskeleton.
AB  - In this paper, we summarize a novel approach to robotic rehabilitation that
      capitalizes on the benefits of patient intent and real-time assessment of
      impairment. Specifically, an upper-limb, physical human-robot interface (the MAHI
      EXO-II robotic exoskeleton) is augmented with a non-invasive brain-machine
      interface (BMI) to include the patient in the control loop, thereby making the
      therapy 'active' and engaging patients across a broad spectrum of impairment
      severity in the rehabilitation tasks. Robotic measures of motor impairment are
      derived from real-time sensor data from the MAHI EXO-II and the BMI. These
      measures can be validated through correlation with widely used clinical measures
      and used to drive patient-specific therapy sessions adapted to the capabilities
      of the individual, with the MAHI EXO-II providing assistance or challenging the
      participant as appropriate to maximize rehabilitation outcomes. This approach to
      robotic rehabilitation takes a step towards the seamless integration of BMIs and
      intelligent exoskeletons to create systems that can monitor and interface with
      brain activity and movement. Such systems will enable more focused study of
      various issues in development of devices and rehabilitation strategies, including
      interpretation of measurement data from a variety of sources, exploration of
      hypotheses regarding large scale brain function during robotic rehabilitation,
      and optimization of device design and training programs for restoring upper limb
      function after stroke.

PMID- 24887298
TI  - Hemoglobinuric acute kidney injury from aortic root graft malfunction.
AB  - Hemolysis and consequent hemoglobinuria is a well-known cause of acute kidney
      injury (AKI). Hemolysis has been associated with malpositioned prosthetic valves,
      but other prosthetic devices may rarely be associated with red cell shear stress.
      We report a case of a 56-year-old man who presented with hemolysis, AKI, and
      anemia. During workup, he was found to have anti-phospholipid antibodies, leading
      to a presumptive diagnosis of catastrophic anti-phospholipid antibody syndrome.
      However, further investigation revealed the cause of hemolysis to be from aortic
      root graft dysfunction. Following replacement of the prosthesis, there was
      complete resolution of his hemolysis and recovery of renal function. This case
      underscores the need to consider cardiac prosthetic devices in patients
      presenting with hemoglobinuric AKI.

PMID- 24887299
TI  - Association of clustering of major cardiovascular risk factors with chronic
      kidney disease in the adult population.
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) is high in China, as
      is the clustering of major cardiovascular (CVD) risk factors. We aimed to explore
      the association of clustering of CVD risk factors with CKD in the adult
      population. METHODS: A total of 3,287 adults who visited the Health Checkup
      Clinic were consecutively enrolled in the study. We investigated the clustering
      of four CVD risk factors (defined as two or more of the following: hypertension,
      diabetes, dyslipidemia, and overweight) and their association with CKD. CKD was
      defined as decreased estimated glomerular filtration rate (eGFR < 60 mL/min/1.73
      m2) or the presence of albuminuria (urinary albumin-to-creatinine >= 30 mg/g).
      RESULTS: Among the total participants in this study, only 27.4% were free of any
      pre-defined CVD risk factors, and 46% of them had clustering of CVD risk factors.
      The prevalence of decreased eGFR, albuminuria, and the overall prevalence of CKD
      in the group of clustering of CVD risk factors was higher than in the group of
      none or in the group of single CVD risk factors, which were 4.9% vs. 1.0% and
      1.8% (p < 0.001), 9.0% vs. 4.1% and 4.0% (p < 0.001), 12.8% vs. 5.1% and 5.8% (p
      < 0.001), respectively. After being adjusted for potential confounders, the
      clustering of CVD risk factors was positively associated with either albuminuria
      or CKD,with odds ratio of 1.93 (95% confidence interval [CI], 1.39 - 2.68) and
      1.72 (95%CI, 1.29 - 2.28). CONCLUSIONS: Clustering of CVD risk factors was
      positively associated with CKD, which further confirms the importance of
      modifying lifestyle to reduce the burden of CKD. *contributed equally to this
      work.

PMID- 24887297
TI  - Polarity gene alterations in pure invasive micropapillary carcinomas of the
      breast.
AB  - INTRODUCTION: Pure invasive micropapillary carcinoma (IMPC) is a special type of
      breast carcinoma characterised by clusters of cells presenting polarity
      abnormalities. The biological alterations underlying this pattern remain unknown.
      METHODS: Pangenomic analysis (n=39), TP53 (n=43) and PIK3CA (n=41) sequencing in
      a series of IMPCs were performed. A subset of cases was also analysed with whole
      exome sequencing (n=4) and RNA sequencing (n=6). Copy number variation profiles
      were compared with those of oestrogen receptors and grade-matched invasive ductal
      carcinomas (IDCs) of no special type. RESULTS: Unsupervised analysis of genomic
      data distinguished two IMPC subsets: one (Sawtooth/8/16) exhibited a significant
      increase in 16p gains (71%), and the other (Firestorm/Amplifier) was
      characterised by a high frequency of 8q (35%), 17q (20% to 46%) and 20q (23% to
      30%) amplifications and 17p loss (74%). TP53 mutations (10%) were more frequently
      identified in the amplifier subset, and PIK3CA mutations (4%) were detected in
      both subsets. Compared to IDC, IMPC exhibited specific loss of the 6q16-q22
      region (45%), which is associated with downregulation of FOXO3 and SEC63 gene
      expression. SEC63 and FOXO3 missense mutations were identified in one case each
      (2%). Whole-exome sequencing combined with RNA sequencing of IMPC allowed us to
      identify somatic mutations in genes involved in polarity, DNAH9 and FMN2 (8% and
      2%, respectively) or ciliogenesis, BBS12 and BBS9 (2% each) or genes coding for
      endoplasmic reticulum protein, HSP90B1 and SPTLC3 (2% each) and cytoskeleton,
      UBR4 and PTPN21 (2% each), regardless of the genomic subset. The intracellular
      biological function of the mutated genes identified by gene ontology analysis
      suggests a driving role in the clinicopathological characteristics of IMPC.
      CONCLUSION: In our comprehensive molecular analysis of IMPC, we identified
      numerous genomic alterations without any recurrent fusion genes. Recurrent
      somatic mutations of genes participating in cellular polarity and shape suggest
      that they, together with other biological alterations (such as epigenetic
      modifications and stromal alterations), could contribute to the morphological
      pattern of IMPC. Though none of the individual abnormalities demonstrated
      specificity for IMPC, whether their combination in IMPC may have a cumulative
      effect that drives the abnormal polarity of IMPC needs to be examined further
      with in vitro experiments.

PMID- 24887300
TI  - Continuous veno-venous hemofiltration to adjust fluid volume excess in septic
      shock patients reduces intra-abdominal pressure.
AB  - OBJECTIVE: To analyze the effect and the time course of continuous veno-venous
      hemofiltration (CVVH) with net ultrafiltration (UF) on intra-abdominal pressure
      (IAP) body fluid volumes in septic shock patients with acute kidney injury (AKI).
      METHODS: Patients were studied at baseline and after 6, 12, 24, 48, 72, and 96
      hours of CVVH treatment. IAP was measured via the bladder, and abdominal
      perfusion pressure (APP) was calculated as mean arterial pressure minus IAP.
      Fluid volume excess (VE), total body water (TBW), extracellular body water (ECW),
      and intracellular body water (ICW) were derived from wholebody bioimpedance
      analysis (BIA). RESULTS: 30 patients entered final analysis, of which 6 died
      during CVVH (non-survivors). Fluid VE, TBW, ECW, ICW, and IAP significantly
      decreased in 24 survivors, whereas these variables remained essentially
      unchangedin non-survivors. APP slowly increased in survivors, while it did not
      change in nonsurvivors. IAP strongly correlated with VEin survivors: The lower
      the IAP, the lower the fluid volume excess. CONCLUSION: CVVH with net UF
      successfully reduced IAP, TBW, ECW, and ICW in critically ill patients who
      survived 96 h of CVVH. Failure to increase APP was associated with fatal outcome,
      and, finally, IAP correlated with fluid volume excess. BIA could be helpful to
      monitor fluid status in patients with AKI.

PMID- 24887301
TI  - Proteinuria is a simple sign of systemic inflammation that leads to a poor
      prognosis in individuals affected with non-Hodgkin lymphoma.
AB  - BACKGROUND: The clinical significance of proteinuria has not been fully
      understood among patients who are affected with non-Hodgkin lymphoma (NHL).
      METHODS: A 1-year prospective cohort study was conducted to ascertain the
      association between proteinuria and mortality in 46 hospitalized NHL patients.
      Proteinuria was defined as persistent dipstick test >= 1+, and the urinary
      protein creatinine ratio (UPCR),as a quantitative index of protein excretion, was
      measured simultaneously. A multivariable linear regression model was constructed
      to determine factors associated with UPCR. Statistical associations between
      proteinuria and time to mortality were analyzed using the Kaplan-Meier method and
      multivariable proportional hazards regression analysis, adjusted for covariates
      including disease severity, renal function, and serum interleukin-6(IL-6)
      concentration. RESULTS: The prevalence of proteinuria was 15.2% in the NHL
      patients. UPCR was significantly associated with the serum IL-6 level
      (standardized beta = 0.360, p = 0.0440). The cumulative mortality was
      significantly higher in proteinuric patients than in non-proteinuric patients,
      with a graded relationship between the severity of UPCR and mortality. The
      mortality risk increased with increasing UPCR grade: the hazard ratio (95%
      confidence interval) was 4.90 (1.29 - 32.3) for UPCR 30 - 300 mg/gand 17.8 (2.84 
      150) for UPCR > 300 mg/g, respectively, when UPCR < 30 mg/g was set as the
      reference. CONCLUSIONS: Proteinuria is a simple sign of coexisting systemic
      inflammation due to NHL and a harbinger of a poor prognosis.

PMID- 24887302
TI  - Practice patterns of phosphate binder use and their associations with mortality
      in chronic kidney disease.
AB  - BACKGROUND: Higher serum phosphorus is associated with an increased mortality
      among those with chronic kidney disease (CKD). We examined the practice patterns
      of phosphate binder use to lower serum phosphorus levels and their associations
      with mortality in the non-dialysisdependent CKD population. METHODS: We examined
      the factors associated with the use of calcium and non-calcium phosphate binders
      in those with stage 3 and 4 CKD (eGFR 15 - 59 mL/min/1.73 m2) using logistic
      regression models. The associations between phosphate binder use and mortality
      were studied using propensity based analysis. RESULTS: Out of 57,928 patients
      with eGFR 15 - 59 mL/min/1.73 m2, 13,325 (23%) patients had serum phosphorus
      levels measured. 945 patients were prescribed phosphate binders, with 238 (25%)
      of them prescribed non-calcium-based phosphate binders and the rest calcium-based
      phosphate binders. Higher BMI, higher serum phosphorus, and higher serum calcium
      were associated with higher odds of being prescribed a non-calcium-based binder.
      Phosphate binder use was not significantly associated with mortality in either
      the entire cohort or the matched cohort in the analysis limited to those who were
      treated for at least 6 months. In the matched cohort, those who were treated for
      1 year with a phosphate binder had a non-significant lower mortality rate (hazard
      ratio (HR): 0.85, 95% CI 0.66, 1.10). CONCLUSIONS: Phosphate binder use for 6
      months and 1 year was not associated with reduced mortality in those with stage 3
      and stage 4 CKD.

PMID- 24887303
TI  - Differential effects of omeprazole and lansoprazole enantiomers on aryl
      hydrocarbon receptor in human hepatocytes and cell lines.
AB  - Proton pump inhibitors omeprazole and lansoprazole contain chiral sulfur atom and
      they are administered as a racemate, i.e. equimolar mixture of S- and R
      enantiomers. The enantiopure drugs esomeprazole and dexlansoprazole have been
      developed and introduced to clinical practice due to their improved clinical and
      therapeutic properties. Since omeprazole and lansoprazole are activators of aryl
      hydrocarbon receptor (AhR) and inducers of CYP1A genes, we examined their
      enantiospecific effects on AhR-CYP1A pathway in human cancer cells and primary
      human hepatocytes. We performed gene reporter assays for transcriptional activity
      of AhR, RT-PCR analyses for CYP1A1/2 mRNAs, western blots for CYP1A1/2 proteins
      and EROD assay for CYP1A1/2 catalytic activity. Lansoprazole and omeprazole
      enantiomers displayed differential effects on AhR-CYP1A1/2 pathway. In general, S
      enantiomers were stronger activators of AhR and inducers of CYP1A genes as
      compared to R-enantiomers in lower concentrations, i.e. 1-10 uM for lansoprazole
      and 10-100 uM for omeprazole. In contrast, R-enantiomers were stronger AhR
      activators and CYP1A inducers than S-enantiomers in higher concentrations, i.e.
      100 uM for lansoprazole and 250 uM for omeprazole. In conclusion, we provide the
      first evidence of enantiospecific effects of omeprazole and lansoprazole on AhR
      signaling pathway. 

PMID- 24887304
TI  - Effects of ranolazine on quality of life among patients with diabetes mellitus
      and stable angina.

PMID- 24887305
TI  - Pulmonary Langerhans cell histiocytosis masquerading as adenocarcinoma of the
      lung.

PMID- 24887306
TI  - Pulmonary langerhans cell histiocytosis.

PMID- 24887307
TI  - c-Ski inhibits autophagy of vascular smooth muscle cells induced by oxLDL and
      PDGF.
AB  - Autophagy is increasingly being recognized as a critical determinant of vascular
      smooth muscle cell (VSMC) biology. Previously, we have demonstrated that c-Ski
      inhibits VSMC proliferation stimulated by transforming growth factor beta (TGF
      beta), but it is not clear whether c-Ski has the similar protective role against
      other vascular injury factors and whether regulation of autophagy is involved in
      its protective effects on VSMC. Accordingly, in this study, rat aortic A10 VSMCs
      were treated with 40 ug/ml oxidized low-density lipoprotein (oxLDL) or 20 ng/ml
      platelet-derived growth factor (PDGF), both of which were autophagy inducers and
      closely related to the abnormal proliferation of VSMCs. Overexpression of c-Ski
      in A10 cells significantly suppressed the oxLDL- and PDGF- induced autophagy.
      This action of c-Ski resulted in inhibiting the cell proliferation, the decrease
      of contractile phenotype marker alpha-SMA expression while the increase of
      synthetic phenotype marker osteopontin expression stimulated by oxLDL or PDGF.
      Inversely, knockdown of c-Ski by RNAi enhanced the stimulatory effects of oxLDL
      or PDGF on A10 cell growth and phenotype transition. And further investigation
      found that inhibition of AKT phosphorylation to downregulate proliferating cell
      nuclear antigen (PCNA) expression, was involved in the regulation of autophagy
      and associated functions by c-Ski in the oxLDL- and PDGF-stimulated VSMCs.
      Collectively, c-Ski may play an important role in inhibiting autophagy to protect
      VSMCs against some harsh stress including oxLDL and PDGF. 

PMID- 24887308
TI  - Thyroid nodules in childhood: indications for biopsy and surgery.
AB  - Aims of this commentary is to report the most recent views about epidemiology,
      diagnostic procedures, malignancy risk factors and clinical management of thyroid
      nodules in children. On the basis of our personal experiences and recent
      literature evidences, we conclude that: a) if nodule is accompanied by
      lymphadenopathy and/or other alert findings, fine-needle aspiration biopsy (FNAB)
      should be recommended; b) if no lymphadenopathy and no other clinical and
      ultrasonographic alert signs are observed, work-up can progress to FNAB only if
      nodule persists or grows over time, even under levo-thyroxine therapy. 

PMID- 24887309
TI  - New insights into the mechanisms involved in B-type natriuretic peptide elevation
      and its prognostic value in septic patients.
AB  - INTRODUCTION: Elevated plasma B-type natriuretic peptide (BNP) levels in patients
      with critical sepsis (severe sepsis and septic shock) may indicate septic
      cardiomyopathy. However, multiple heterogeneous conditions may also be involved
      in increased BNP level. In addition, the prognostic value of BNP in sepsis
      remains debatable. In this study, we sought to discover potential independent
      determinants of BNP elevation in critical sepsis. The prognostic value of BNP was
      also evaluated. METHODS: In this observational study, we enrolled mechanically
      ventilated, critically septic patients requiring hemodynamic monitoring through a
      pulmonary artery catheter. All clinical, laboratory and survival data were
      prospectively collected. Plasma BNP concentrations were measured daily for five
      consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of
      left and right ventricular ejection fractions (EF) derived from echocardiography
      and thermodilution, respectively. Mortality was recorded at day 28. RESULTS: A
      total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were
      ultimately enrolled. Daily BNP levels were significantly elevated in septic shock
      patients compared with those with severe sepsis (P <=0.002). Critical illness
      severity (assessed by Acute Physiology and Chronic Health Evaluation II and
      maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose
      on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular
      EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but
      not independently. Pulmonary capillary wedge pressures (PCWP) and volume
      expansion showed no correlation with BNP. In septic shock, increased central
      venous pressure (CVP) and CVP/PCWP ratio were independently associated with early
      BNP values (P <0.05). CONCLUSIONS: The severity of critical illness, rather than
      septic cardiomyopathy, is probably the major determinant of BNP elevation in
      patients with critical sepsis. Daily BNP values are of limited prognostic value
      in predicting 28-day mortality; however, fast BNP decline over time and a
      decrease in BNP <500 pg/ml may imply a favorable outcome.

PMID- 24887310
TI  - Knowledge and beliefs on antimicrobial resistance among physicians and nurses in
      hospitals in Amhara Region, Ethiopia.
AB  - BACKGROUND: Antimicrobial resistance (AMR) is a major global public health
      problem both in hospital and community acquired infections. The present study
      assessed the knowledge and beliefs on AMR among physicians and nurses in 13
      hospitals in Amhara region, Ethiopia, which is a low-income country. METHODS: A
      cross-sectional study using a self-administered questionnaire was applied.
      RESULTS: A total of 385 participants (175 physicians and 210 nurses) took part in
      the study. Sixty five percent of physicians and 98% of nurses replied that they
      need training on antimicrobial stewardship. Only 48% of physicians and 22.8% of
      nurses had exposures for local antibiogram data. Overall, 278 (72.2%) of
      participants were knowledgeable about AMR. Majority of participants agreed or
      strongly agreed AMR as worldwide and national problem but few considered AMR as
      problem in their own hospitals. The two most important factors mentioned for AMR
      development were patients' poor adherence to prescribed antimicrobials (86%) and
      overuse of antibiotics (80.5%). The most leading local factors identified for AMR
      development were: self-antibiotic prescription (53.5%), lack of access to local
      antibiogram data (12.3%) and prescriber poor awareness about AMR (9.2%). Factors
      perceived for excessive antibiotic prescriptions were: patient drive (56%),
      treatment failure (79%), unknown febrile illnesses (39.7%) and upper respiratory
      tract infections (33.4%). CONCLUSION: Majority of physicians and nurses lack up
      to-date knowledge on AMR. Unavailability of local antibiogram data, self
      prescription by patients and poor awareness on AMR are areas of interventions for
      prevention and control of AMR.

PMID- 24887314
TI  - Raman identification of edge alignment of bilayer graphene down to the nanometer
      scale.
AB  - The ideal edges of bilayer graphene (BLG) are that the edges of the top and
      bottom graphene layers (GLs) of BLG are well-aligned. Actually, the alignment
      distance between the edges of the top and bottom GLs of a real BLG can be as
      large as the submicrometer scale or as small as zero, which cannot be
      distinguished using an optical microscope. Here, we present a detailed Raman
      study on BLG at its edges. If the alignment distance of the top and bottom GLs of
      BLG is larger than the laser spot, the measured D mode at the edge of the top GL
      of BLG shows a similar spectral profile to that of disordered BLG. If the
      alignment distance is smaller than the laser spot, the D mode at a real BLG edge
      shows three typical spectral profiles similar to that at the edge of SLG, that of
      the well-aligned edge of BLG, or a combination of both. We show the sensitivity
      and ability of Raman spectroscopy to acquire the alignment distance between two
      edges of top and bottom GLs of BLG as small as several nanometers, which is far
      beyond the diffraction limit of a laser spot. This work opens the possibility to
      probe the edge alignment of multi-layer graphene. 

PMID- 24887313
TI  - Synergistic activity of tenofovir and nevirapine combinations released from
      polycaprolactone matrices for potential enhanced prevention of HIV infection
      through the vaginal route.
AB  - Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral
      agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide
      synergistic activity in the prevention of HIV transmission through the vaginal
      route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of
      10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL
      content of the matrices. Actual TFV loadings ranged from 2.1% to 4.2% equating to
      loading efficiencies of about 41-42%. The actual loadings of NVP were around half
      those of TFV (1.2-1.9%), resulting in loading efficiencies ranging from 17.2% to
      23.5%. Approximately 80% of the initial content of TFV was released from the PCL
      matrices into simulated vaginal fluid (SVF) over a period of 30 days, which was
      almost double the cumulative release of NVP (40-45%). The release kinetics of
      both antivirals over 30 days were found to be described most satisfactorily by
      the Higuchi model. In vitro assay of release media containing combinations of TFV
      and NVP released from PCL matrices confirmed a potential synergistic/additive
      effect of the released antivirals on HIV-1 infection of HeLa cells. These
      findings indicate that PCL matrices loaded with combinations of TFV and NVP
      provide an effective strategy for the sustained vaginal delivery of antivirals
      with synergistic/additive activity.

PMID- 24887315
TI  - Are context-specific measures of parental-reported physical activity and
      sedentary behaviour associated with accelerometer data in 2-9-year-old European
      children?
AB  - OBJECTIVE: The aim of the present study was to investigate if context-specific
      measures of parental-reported physical activity and sedentary behaviour are
      associated with objectively measured physical activity and sedentary time in
      children. DESIGN: Cross-sectional study. SETTING: Seven European countries taking
      part in the IDEFICS (Identification and Prevention of Dietary- and Lifestyle
      induced Health Effects in Children and Infants) study. SUBJECTS: Data were
      analysed from 2-9-year-old children (n 5982) who provided both parental-reported
      and accelerometer-derived physical activity/sedentary behaviour measures. Parents
      reported their children's daily screen-time, weekly sports participation and
      daily outdoor playtime by means of the Outdoor Playtime Checklist (OPC) and
      Outdoor Playtime Recall Questions (OPRQ). RESULTS: Sports participation, OPC- and
      OPRQ-derived outdoor play were positively associated with accelerometer-derived
      physical activity. Television viewing and computer use were positively associated
      with accelerometer-derived sedentary time. All parental-reported measures that
      were significantly associated with accelerometer outcomes explained only a minor
      part of the variance in accelerometer-derived physical activity or sedentary
      time. CONCLUSIONS: Parental-reported measures of physical activity and sedentary
      behaviour are not useful as a proxy for 2-9-year-old children's physical activity
      and sedentary time. Findings do not preclude the use of context-specific measures
      but imply that conclusions should be limited to the context-specific behaviours
      that are actually measured. Depending on the aim of the study, future research
      should carefully consider the choice of measurements, including the use of
      subjective or objective measures of the behaviour of interest or a combination of
      both.

PMID- 24887312
TI  - Identification of novel SHOX target genes in the developing limb using a
      transgenic mouse model.
AB  - Deficiency of the human short stature homeobox-containing gene (SHOX) has been
      identified in several disorders characterized by reduced height and skeletal
      anomalies such as Turner syndrome, Leri-Weill dyschondrosteosis and Langer
      mesomelic dysplasia as well as isolated short stature. SHOX acts as a
      transcription factor during limb development and is expressed in chondrocytes of
      the growth plates. Although highly conserved in vertebrates, rodents lack a SHOX
      orthologue. This offers the unique opportunity to analyze the effects of human
      SHOX expression in transgenic mice. We have generated a mouse expressing the
      human SHOXa cDNA under the control of a murine Col2a1 promoter and enhancer
      (Tg(Col2a1-SHOX)). SHOX and marker gene expression as well as skeletal phenotypes
      were characterized in two transgenic lines. No significant skeletal anomalies
      were found in transgenic compared to wildtype mice. Quantitative and in situ
      hybridization analyses revealed that Tg(Col2a1-SHOX), however, affected
      extracellular matrix gene expression during early limb development, suggesting a
      role for SHOX in growth plate assembly and extracellular matrix composition
      during long bone development. For instance, we could show that the connective
      tissue growth factor gene Ctgf, a gene involved in chondrogenic and angiogenic
      differentiation, is transcriptionally regulated by SHOX in transgenic mice. This
      finding was confirmed in human NHDF and U2OS cells and chicken micromass culture,
      demonstrating the value of the SHOX-transgenic mouse for the characterization of
      SHOX-dependent genes and pathways in early limb development. 

PMID- 24887316
TI  - iRFP is a real time marker for transformation based assays in high content
      screening.
AB  - Anchorage independent growth is one of the hallmarks of oncogenic transformation.
      Here we show that infrared fluorescent protein (iRFP) based assays allow accurate
      and unbiased determination of colony formation and anchorage independent growth
      over time. This protocol is particularly compatible with high throughput systems,
      in contrast to traditional methods which are often labor-intensive, subjective to
      bias and do not allow further analysis using the same cells. Transformation in a
      single layer soft agar assay could be documented as early as 2 to 3 days in a 96
      well format, which can be easily combined with standard transfection, infection
      and compound screening setups to allow for high throughput screening to identify
      therapeutic targets. 

PMID- 24887317
TI  - Rubella monitoring in pregnancy as a means for evaluating a possible reemergence
      of rubella.
AB  - OBJECTIVE: Although it is commonly accepted that rubella is well-controlled, a
      recent reemergence of both pertussis and measles might also predict a reemergence
      of rubella. This study was designed to estimate the current incidence of rubella
      exposure in pregnancy. STUDY DESIGN: This was a prospective, descriptive study,
      conducted in Houston, TX, at The Woman's Hospital of Texas. Women are typically
      screened for rubella immunity at the beginning of pregnancy. Rubella nonimmunity
      is defined as a titer less than 10 IU/mL in the US. Women who were non-immune
      early in pregnancy (<20 weeks) were recruited for this study and asked to be
      tested again for rubella immunity at the time of delivery. RESULTS: Of 298 women
      who were rubella nonimmune (IgG <10 IU/mL) early in pregnancy, 19 converted to
      immune status (IgG >40 IU/mL, defined as at least a 4-fold increase) at time of
      delivery, a rate of 6.38% (4.12% to 9.75%; 95% Wilson-Score confidence interval).
      For the 19 patients who converted to immune status at time of delivery, 8
      patients had levels of 40-150 IU/mL, 6 patients had levels of 151-300 IU/mL, 2
      patients had levels of 301-500 IU/mL, and 3 patients had levels >500 IU/mL.
      CONCLUSION: Pregnancy is a critical time to evaluate rubella exposure. This study
      estimated the current incidence of rubella exposure in pregnancy to be 6.38%.

PMID- 24887318
TI  - Loop electrosurgical excision procedure: an effective, inexpensive, and durable
      teaching model.
AB  - The effectiveness of simulation training for enhancing operative skills is well
      established. Here we describe the construction of a simple, low-cost model for
      teaching the loop electrosurgical excision procedure. Composed of common
      materials such as polyvinyl chloride pipe and sausages, the simulation model,
      shown in the accompanying figure, can be easily reproduced by other training
      programs. In addition, we also present an instructional video that utilizes this
      model to review loop electrosurgical excision procedure techniques, highlighting
      important steps in the procedure and briefly addressing challenging situations
      and common mistakes as well as strategies to prevent them. The video and model
      can be used in conjunction with a simulation skills laboratory to teach the
      procedure to students, residents, and new practitioners. 

PMID- 24887319
TI  - Electronic fetal heart rate monitoring (EFM) credentialing examination-pros and
      cons.

PMID- 24887322
TI  - pH-responsive self-assembly of fluorophore-ended homopolymers.
AB  - pH-responsive perylene-ended amphiphilic homopolymers can self-assemble into
      flower-like structures by pH-adjustment. Both the pi-pi stacking of perylene end
      groups and the electrostatic repulsion effect of the polymer chains contribute to
      the pH-responsive self-assembly in aqueous solution. 

PMID- 24887320
TI  - Hypoxic pulmonary hypertension: the paradigm is changing.

PMID- 24887323
TI  - Cross-reaction of propyl and butyl alcohol glucuronides with an ethyl glucuronide
      enzyme immunoassay.
AB  - BACKGROUND: Ethyl glucuronide (EtG) in urine is considered a marker of recent
      alcohol consumption. Using immunoassays for EtG screening without confirmatory
      analysis bears a risk of getting false-positives as shown for trichloroethyl
      glucuronide from chloral hydrate medication and 1-propyl glucuronide from
      propanol-based hand disinfection. The aim of the study was to check whether
      glucuronides of frequently used aliphatic short chain alcohols aside from EtG and
      1-propyl glucuronide can cross-react with the DRI((r)) Ethyl Glucuronide Assay.
      METHODS: Aliquots of EtG-free urine were individually spiked with methyl beta-D
      glucuronide, 1-propyl beta-D-glucuronide, 2-propyl beta-D-glucuronide, 1-butyl
      beta-D-glucuronide, 2-butyl beta-D-glucuronide, and tert-butyl beta-D
      glucuronide. To check the response rate of the DRI((r)) Ethyl Glucuronide Assay
      to its target analyte, EtG was also added to a native EtG-free urine sample. The
      spiked alcohol glucuronide concentrations (seven levels up to 10mg/L) and the
      DRI((r)) Ethyl Glucuronide Assay results were evaluated by Passing-Bablok
      regression analysis. The 95% confidence interval ranges for the slope of the
      regression function were considered a measure of cross-reaction of the individual
      alcohol glucuronides with the enzyme immunoassay. RESULTS: 2-Propyl glucuronide
      showed a cross-reactivity of 69-84% at the 95% probability level, methyl
      glucuronide, 1-propyl glucuronide, and 1- and 2-butyl glucuronide of 4-9%, and
      tert-butyl glucuronide almost no cross-reactivity. The response rate for EtG was
      87-94% at the 95% probability level. CONCLUSION: The DRI((r)) Ethyl Glucuronide
      Assay shows cross-reaction rates with aliphatic short chain alcohol glucuronides
      aside from EtG which bear a risk of getting false-positives regarding ethanol
      consumption. Mass spectrometric detection of EtG is mandatory for confirmation of
      positive immunological EtG screenings.

PMID- 24887324
TI  - Morphine and codeine concentrations in human urine following controlled poppy
      seeds administration of known opiate content.
AB  - Opiates are an important component for drug testing due to their high abuse
      potential. Proper urine opiate interpretation includes ruling out poppy seed
      ingestion; however, detailed elimination studies after controlled poppy seed
      administration with known morphine and codeine doses are not available.
      Therefore, we investigated urine opiate pharmacokinetics after controlled oral
      administration of uncooked poppy seeds with known morphine and codeine content.
      Participants were administered two 45 g oral poppy seed doses 8 h apart, each
      containing 15.7 mg morphine and 3mg codeine. Urine was collected ad libitum up to
      32 h after the first dose. Specimens were analyzed with the Roche Opiates II
      immunoassay at 2000 and 300 MUg/L cutoffs, and the ThermoFisher CEDIA((r)) heroin
      metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10 MUg/L
      cutoffs to determine if poppy seed ingestion could produce positive results in
      these heroin marker assays. In addition, all specimens were quantified for
      morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens
      over 32 h following dosing; 26.6% and 83.4% were positive for morphine at 2000
      and 300 MUg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the
      study, morphine concentrations ranged from <300 to 7522 MUg/L with a median peak
      concentration of 5239 MUg/L. The median first morphine-positive urine sample at
      2000 MUg/L cutoff concentration occurred at 6.6 h (1.2-12.1), with the last
      positive from 2.6 to 18 h after the second dose. No specimens were positive for
      codeine at a cutoff concentration of 2000 MUg/L, but 20.2% exceeded 300 MUg/L,
      with peak concentrations of 658 MUg/L (284-1540). The Roche Opiates II
      immunoassay had efficiencies greater than 96% for the 2000 and 300 MUg/L cutoffs.
      The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had
      no false positive results. These data provide valuable information for
      interpreting urine opiate results.

PMID- 24887325
TI  - Effective health care for older people resident in care homes: the optimal study
      protocol for realist review.
AB  - BACKGROUND: Care homes in the UK rely on general practice for access to
      specialist medical and nursing care as well as referral to therapists and
      secondary care. Service delivery to care homes is highly variable in both
      quantity and quality. This variability is also evident in the commissioning and
      organisation of care home-specific services that range from the payment of
      incentives to general practitioners (GPs) to visit care homes, to the creation of
      care home specialist teams and outreach services run by geriatricians. No primary
      studies or systematic reviews have robustly evaluated the impact of these
      different approaches on organisation and resident-level outcomes. Our aim is to
      identify factors which may explain the perceived or demonstrated effectiveness of
      programmes to improve health-related outcomes in older people living in care
      homes. METHODS/DESIGN: A realist review approach will be used to develop a
      theoretical understanding of what works when, why and in what circumstances.
      Elements of service models of interest include those that focus on assessment and
      management of residents' health, those that use strategies to encourage closer
      working between visiting health care providers and care home staff, and those
      that address system-wide issues about access to assessment and treatment. These
      will include studies on continence, dignity, and speech and language assessment
      as well as interventions to promote person centred dementia care, improve
      strength and mobility, and nutrition. The impact of these interventions and their
      different mechanisms will be considered in relation to five key outcomes:
      residents' medication use, use of out of hours' services, hospital admissions
      (including use of Accident and Emergency) and length of hospital stay, costs and
      user satisfaction. An iterative three-stage approach will be undertaken that is
      stakeholder-driven and optimises the knowledge and networks of the research team.
      DISCUSSION: This realist review will explore why and for whom different
      approaches to providing health care to residents in care homes improves access to
      health care in the five areas of interest. It will inform commissioning decisions
      and be the basis for further research. This systematic review protocol is
      registered on the PROSPERO database reference number: CRD42014009112.

PMID- 24887328
TI  - Overlapping biological mechanisms underlying sickle cell disease, stress, and
      depression: a stress-vulnerability framework.
AB  - LEARNING OBJECTIVES: After participating in this activity, learners should be
      better able to:1. Evaluate the overlap between sickle cell disease (SCD) and
      depression.2. Identify sources of psychological stress and biological
      vulnerabilities toward developing depression in patients with SCD.3. Assess the
      potential mechanisms underlying SCD, stress, and depression.Depression is a
      common co-occurring disorder in persons with sickle-cell disease (SCD).
      Individuals with this chronic illness may be particularly vulnerable to
      depression. In addition to risk factors for depression specifically related to
      SCD, these individuals typically experience further psychological stress due to
      multiple risk factors in their environment. To date, however, little research has
      focused on the co-occurring biological mechanisms across these conditions and how
      those mechanisms may interact to produce depressive symptoms. In this review we
      use a stress-vulnerability framework to describe the sources of psychological
      stress and the SCD factors that increase the risk of depression. We suggest that
      several biological factors, such as nitric oxide and cytokines, may play an
      important role in co-occurring stress, SCD, and depression. The interaction of
      these factors may be of particular importance for understanding the comorbidity
      of SCD and depression. Implications for current treatment and future research are
      discussed.

PMID- 24887327
TI  - Comparative examination of various PCR-based methods for DNMT3A and IDH1/2
      mutations identification in acute myeloid leukemia.
AB  - BACKGROUND: Mutations in epigenetic modifiers were reported in patients with
      acute myeloid leukaemia (AML) including mutations in DNA methyltransferase 3A
      gene (DNMT3A) in 20%-30% patients and mutations in isocitrate dehydrogenase 1/2
      gene (IDH1/2) in 5%-15% patients. Novel studies have shown that mutations in
      DNMT3A and IDH1/2 influence prognosis, indicating an increasing need to detect
      these mutations during routine laboratory analysis. DNA sequencing for the
      identification of these mutations is time-consuming and cost-intensive. This
      study aimed to establish rapid screening tests to identify mutations in DNMT3A
      and IDH1/2 that could be applied in routine laboratory procedures and that could
      influence initial patient management. METHODS: In this study we developed an
      endonuclease restriction method to identify the most common DNMT3A mutation
      (R882H) and an amplification-refractory mutation system (ARMS) to analyse IDH2
      R140Q mutations. Furthermore, we compared these methods with HRM analysis and
      evaluated the latter for the detection of IDH1 mutations. RESULTS: Of 230 samples
      from patients with AML 30 (13%) samples had DNMT3A mutations, 16 (7%) samples had
      IDH2 R140Q mutations and 36 (16%) samples had IDH1 mutations. Sensitivity assays
      performed using serial dilutions of mutated DNA showed that ARMS analysis had a
      sensitivity of 4.5%, endonuclease restriction had a sensitivity of 0.05% and HRM
      analysis had a sensitivity of 5.9%-7.8% for detecting different mutations. HRM
      analysis was the best screening method to determine the heterogeneity of IDH1
      mutations. Furthermore, for the identification of mutations in IDH2 and DNMT3A,
      endonuclease restriction and ARMS methods showed a perfect concordance (100%)
      with Sanger sequencing while HRM analysis showed a near-perfect concordance
      (approximately 98%). CONCLUSION: Our study suggested that all the developed
      methods were rapid, specific and easy to use and interpret. HRM analysis is the
      most timesaving and cost-efficient method to rapidly screen all the 3 genes at
      diagnosis in samples obtained from patients with AML. Endonuclease restriction
      and ARMS assays can be used separately or in combination with HRM analysis to
      obtain more reliable results. We propose that early screening of mutations in
      patients with AML having normal karyotype could facilitate risk stratification
      and improve treatment options.

PMID- 24887326
TI  - Overcoming multiple drug resistance mechanisms in medulloblastoma.
AB  - INTRODUCTION: Medulloblastoma (MB) is the most common malignant paediatric brain
      tumour. Recurrence and progression of disease occurs in 15-20% of standard risk
      and 30-40% of high risk patients. We analysed whether circumvention of
      chemoresistance pathways (drug export, DNA repair and apoptotic inhibition) can
      restore chemotherapeutic efficacy in a panel of MB cell lines. RESULTS: We
      demonstrate, by immunohistochemistry in patient tissue microarrays, that ABCB1 is
      expressed in 43% of tumours and is significantly associated with high-risk. We
      show that ABCB1, O6-methylguanine-DNA-methyltransferase (MGMT) and BCL2 family
      members are differentially expressed (by quantitative reverse transcription
      polymerase chain reaction, Western blotting and flow cytometry) in MB cell lines.
      Based on these findings, each pathway was then inhibited or circumvented and cell
      survival assessed using clonogenic assays. Inhibition of ABCB1 using vardenafil
      or verapamil resulted in a significant increase in sensitivity to etoposide in
      ABCB1-expressing MB cell lines. Sensitivity to temozolomide (TMZ) was MGMT
      dependent, but two novel imidazotetrazine derivatives (N-3 sulfoxide and N-3
      propargyl TMZ analogues) demonstrated >=7 fold and >=3 fold more potent
      cytotoxicity respectively compared to TMZ in MGMT-expressing MB cell lines.
      Activity of the BAD mimetic ABT-737 was BCL2A1 and ABCB1 dependent, whereas the
      pan-BCL2 inhibitor obatoclax was effective as a single cytotoxic agent
      irrespective of MCL1, BCL2, BCL2A1, or ABCB1 expression. CONCLUSIONS: ABCB1 is
      associated with high-risk MB; hence, inhibition of ABCB1 by vardenafil may
      represent a valid approach in these patients. Imidazotetrazine analogues of TMZ
      and the BH3 mimetic obatoclax are promising clinical candidates in drug resistant
      MB tumours expressing MGMT and BCL2 anti-apoptotic members respectively.

PMID- 24887329
TI  - Selection and assessment of reference genes for quantitative PCR normalization in
      migratory locust Locusta migratoria (Orthoptera: Acrididae).
AB  - Locusta migratoria is a classic hemimetamorphosis insect and has caused
      widespread economic damage to crops as a migratory pest. Researches on the
      expression pattern of functional genes in L. migratoria have drawn focus in
      recent years, especially with the release of genome information. Real-time
      quantitative PCR is the most reproducible and sensitive approach for detecting
      transcript expression levels of target genes, but optimal internal standards are
      key factors for its accuracy and reliability. Therefore, it's necessary to
      provide a systematic stability assessment of internal control for well-performed
      tests of target gene expression profile. In this study, twelve candidate genes
      (Ach, Act, Cht2, EF1alpha, RPL32, Hsp70, Tub, RP49, SDH, GAPDH, 18S, and His)
      were analyzed with four statistical methods: the delta Ct approach, geNorm,
      Bestkeeper and NormFinder. The results from these analyses aimed to choose the
      best suitable reference gene across different experimental situations for gene
      profile study in L. migratoria. The result demonstrated that for different
      developmental stages, EF1alpha, Hsp70 and RPL32 exhibited the most stable
      expression status for all samples; EF1alpha and RPL32 were selected as the best
      reference genes for studies involving embryo and larvae stages, while SDH and
      RP49 were identified for adult stage. The best-ranked reference genes across
      different tissues are RPL32, Hsp70 and RP49. For abiotic treatments, the most
      appropriate genes we identified were as follows: Act and SDH for larvae subjected
      to different insecticides; RPL32 and Ach for larvae exposed to different
      temperature treatments; and Act and Ach for larvae suffering from starvation. The
      present report should facilitate future researches on gene expression in L.
      migratoria with accessibly optimal reference genes under different experimental
      contexts. 

PMID- 24887331
TI  - Direct real-time measurement of intra-oocyte nitric oxide concentration in vivo.
AB  - Nitric oxide (NO) is reported to play significant a role in oocyte activation and
      maturation, implantation, and early embryonic development. Previously we have
      shown that NO forms an important component of the oocyte microenvironment, and
      functions effectively to delay oocyte aging. Thus, precise information about
      intra-oocyte NO concentrations [NO] will result in designing more accurate
      treatment plans in assisted reproduction. In this work, the direct, real-time and
      quantitative intra-oocyte [NO] was measured utilizing an L-shaped amperometric
      integrated NO-selective electrode. This method not only provides an elegant and
      convenient approach to real-time the measurement of NO in physiological
      environments, but also mimics the loss of NO caused by rapid NO diffusion
      combined with its reactivity in the biological milieu. This experiment suggests
      that the NO levels of oocytes obtained from young animals are significantly
      higher than those of oocytes obtained from old animals. Additionally the NO
      levels stay constant during the measurements; however, the intra-oocyte [NO] is
      reduced significantly (70-75% reduction) in response to L-NAME incubation,
      suggesting that NO measurements are truly NOS based rather than caused by an
      unknown interfering substance in our system. We believe this first demonstration
      of the direct quantitative measurement of [NO] in situ in an intact cellular
      complex should be useful in tracking real-time and rapid changes at nanomolar
      levels. Moreover, this finding confirms and extends our previous work showing
      that supplementation with NO delays the oocyte aging process. 

PMID- 24887330
TI  - Bacterial diversity assessment in Antarctic terrestrial and aquatic microbial
      mats: a comparison between bidirectional pyrosequencing and cultivation.
AB  - The application of high-throughput sequencing of the 16S rRNA gene has increased
      the size of microbial diversity datasets by several orders of magnitude,
      providing improved access to the rare biosphere compared with cultivation-based
      approaches and more established cultivation-independent techniques. By contrast,
      cultivation-based approaches allow the retrieval of both common and uncommon
      bacteria that can grow in the conditions used and provide access to strains for
      biotechnological applications. We performed bidirectional pyrosequencing of the
      bacterial 16S rRNA gene diversity in two terrestrial and seven aquatic Antarctic
      microbial mat samples previously studied by heterotrophic cultivation. While, not
      unexpectedly, 77.5% of genera recovered by pyrosequencing were not among the
      isolates, 25.6% of the genera picked up by cultivation were not detected by
      pyrosequencing. To allow comparison between both techniques, we focused on the
      five phyla (Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and
      Deinococcus-Thermus) recovered by heterotrophic cultivation. Four of these phyla
      were among the most abundantly recovered by pyrosequencing. Strikingly, there was
      relatively little overlap between cultivation and the forward and reverse
      pyrosequencing-based datasets at the genus (17.1-22.2%) and OTU (3.5-3.6%) level
      (defined on a 97% similarity cut-off level). Comparison of the V1-V2 and V3-V2
      datasets of the 16S rRNA gene revealed remarkable differences in number of OTUs
      and genera recovered. The forward dataset missed 33% of the genera from the
      reverse dataset despite comprising 50% more OTUs, while the reverse dataset did
      not contain 40% of the genera of the forward dataset. Similar observations were
      evident when comparing the forward and reverse cultivation datasets. Our results
      indicate that the region under consideration can have a large impact on perceived
      diversity, and should be considered when comparing different datasets. Finally, a
      high number of OTUs could not be classified using the RDP reference database,
      suggesting the presence of a large amount of novel diversity. 

PMID- 24887334
TI  - Therapeutic adherence to osteoporosis treatment.
AB  - OBJECTIVE: Adherence of patients to therapy is a major determinant of therapeutic
      success, which is not included in most clinical studies. This is especially true
      for chronic diseases with few subjective symptoms, such as osteoporosis. The aim
      of our study was to describe and to analyze the therapeutic adherence to several
      widely used anti-osteoporotic medications in real-world medicine in Slovakia.
      METHODS: Using a retrospective approach, data about drug prescriptions for 8,223
      patients from 3 consecutive years were analyzed regarding compliance and
      persistence. Compliance was measured as medication possession ratio-ratio between
      the supply of the drugs in the treatment time according to the prescriptions and
      the time of observation. Persistence was assessed as the percentage of patients
      who used the drug without a gap for the given time period. RESULTS: The average
      compliance was 70%, 59%, and 4% for 6, 12, and 24 months, respectively. Average
      persistence was very low with 54%, 42%, and 22% for 6, 12, and 24 months,
      respectively. Total average persistence was only 9.8 months. Medications with
      lower frequency of application tended to be associated with higher adherence.
      CONCLUSION: In conclusion, the therapeutic adherence to anti-osteoporotic
      treatments varies between the available drugs and drug regimens. In general, the
      adherence is very low but comparable to previously published studies from other
      countries. This variability of adherence should be considered in clinical
      decision making together with the variability of therapeutic efficiency found in
      clinical studies.

PMID- 24887332
TI  - Contribution of endothelial injury and inflammation in early phase to vein graft
      failure: the causal factors impact on the development of intimal hyperplasia in
      murine models.
AB  - OBJECTIVES: Autologous veins are preferred conduits in by-pass surgery. However,
      long-term results are hampered by limited patency due to intimal hyperplasia.
      Although mechanisms involved in development of intimal hyperplasia have been
      established, the role of inflammatory processes is still unclear. Here, we
      studied leukocyte recruitment and intimal hyperplasia in inferior vena cava
      grafts transferred to abdominal aorta in mice. METHODS AND RESULTS: Several
      microscopic techniques were used to study endothelium denudation and regeneration
      and leukocyte recruitment on endothelium. Scanning electron microscopy
      demonstrated denudation of vein graft endothelium 7 days post-transfer and
      complete endothelial regeneration by 28 days. Examination of vein grafts
      transferred to mice transgenic for green fluorescent protein under Tie2 promoter
      in endothelial cells showed regeneration of graft endothelium from the adjacent
      aorta. Intravital microscopy revealed recruitment of leukocytes in vein grafts at
      7 days in wild type mice, which had tapered off by 28 days. At 28 and 63 days
      there was significant development of intimal hyperplasia. In contrast; no injury,
      leukocyte recruitment nor intimal hyperplasia occurred in arterial grafts.
      Leukocyte recruitment was reduced in vein grafts in mice deficient in E- and P
      selectin. In parallel, intimal hyperplasia was reduced in vein grafts in mice
      deficient in E- and P-selectin and in wild type mice receiving P-selectin/E
      selectin function-blocking antibodies. CONCLUSION: The results show that early
      phase endothelial injury and inflammation are crucial processes in intimal
      hyperplasia in murine vein grafts. The data implicate endothelial selectins as
      targets for intervention of vein graft disease.

PMID- 24887335
TI  - Population pharmacokinetics of oxcarbazepine active metabolite in Chinese
      children with epilepsy.
AB  - OBJECTIVE: This study was to establish the population pharmacokinetic (PPK) model
      of pharmacologically active metabolite of oxcarbazepine (OXC) and to estimate PPK
      parameters for the optimal individuation administration of OXC in Chinese
      children with epilepsy. METHODS: The pharmacologically active metabolite, 10
      monohydroxy derivative of OXC (MHD)was used as the analytical target for
      monitoring therapy of OXC. A total of 840 MHD serum samples from 466 children
      with epilepsy were analyzed using high-performance liquid chromatography with UV
      detection. Patients' clinical data were retrospectively collected. Population
      pharmacokinetics analysis was performed using a non-linear mixed-effect model
      with Phoenix NLME 1.2. Pharmacokinetic parameters were estimated according to a
      one-compartment model with first-order absorption and elimination. Effects of
      age,gender, total body weight (TBW), daily doseper weight (DDPW) and use of
      concomitant antiepileptic drugs (AEDs) were analyzed.Bootstrap and predictive
      check were used simultaneously to validate the final population pharmacokinetics
      models. RESULTS: The final PPK model of MHD was: Ka = 0.645 h-1, V(L) = (11.3 +
      (age - 90.5) x 0.0282 + (TBW - 25.0) x 0.402) x e(0.0689), CL (L/h) = (0.557 +
      (DDPW - 20.8) x 0.00367 + (gender) x (-0.0636)) x e(0.120). The final PPK model
      was demonstrated to be suitable and effective by the bootstrap and predictive
      check. CONCLUSIONS: A PPK model of MHD in Chinese children with epilepsy was
      successfully established. PPK parameters of MHD could be predicted accurately by
      this model. This model may be very useful for establishing individual dosage
      guidelines of OXC in Chinese children with epilepsy.

PMID- 24887333
TI  - Modeling and simulations to confirm a controlled hypoglycemic stress test in
      healthy subjects is not associated with clinically significant QT prolongations.
AB  - OBJECTIVES: A modified insulin tolerance test (ITT) can be used to simulate a
      physiological stress state through the induction of controlled hypoglycemia in
      healthy volunteers. This allows for evaluation of hypothalamic-pituitary
      adrenocortical axis response to stress via a surge in cortical release. However,
      a consequence of severe, prolonged hypoglycemia is QT interval prolongation. The
      aim of this analysis was to confirm that blood glucose lowering to 60 mg/dL
      (previously identified as adequate for inducing stress) has low risk of inducing
      clinically significant QT prolongation. MATERIALS AND METHODS: Continuous ECG
      monitoring was conducted as a planned sub study of an open-label, 2-period study
      involving 18 healthy male subjects. The QTcF response to hypoglycemia was
      measured over 2 identical periods, ~ 7 days apart. RESULTS: An indirect- response
      model adequately described the pharmacological relationship between blood glucose
      and QTcF intervals over the time-course of the ITT. The model correctly
      identified the steep glucose-QT relationship as an on-off response with a large
      Hill coefficient of 59 and the threshold glucose, EC50, as ~ 57 mg/dL with narrow
      between-subject variability of 10%. Simulated QTcF profiles over the course of an
      ITT did not demonstrate any QTcF interval changes of clinical concern, defined as
      QTcF observation > 500 ms, if hypoglycemia did not reach below 60 mg/dL. The
      statistical prediction that the chance of a mean QTcF observation > 500 ms was <
      0.0001. CONCLUSIONS: Results support that an ITT maintained at or above 60 mg/dL
      is unlikely to cause QT prolongation in healthy volunteers and does not warrant
      continuous ECG monitoring in this group of subjects.

PMID- 24887336
TI  - A randomized study of intranasal vs. intravenous infusion of dexmedetomidine in
      gastroscopy.
AB  - OBJECTIVE: To compare the respiratory and circulatory parameters between
      intranasal and intravenous dexmedetomidine in gastroscopy. METHODS: 60 patients
      undergoing elective gastroscopy were randomly divided into group D1 and D2.
      Dexmedetomidine (0.5 ug/kg, 1 mL) and normal saline (NS, 1 mL) were given by
      intranasal route 40 minutes before induction, and then NS (20 mL) and
      dexmedetomidine (0.5 ug/kg, 20 mL) were given intravenously 10 minutes before
      induction, respectively, in groups D1 and D2. Propofol (1.5 - 2 mg/kg) was used
      for induction. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen
      saturation(SpO2), and respiratory rate (RR) were monitored. The latent period of
      falling asleep, the duration of gastroscopy, the time of awakening, and the total
      dose of propofol consumption were also recorded. Postoperative sedation scale and
      adverse reactions were observed. RESULTS: One patient in group D1 was excluded
      from the study due to atrioventricular block. The HR and SpO2 were significantly
      lower, but RR was significantly higher in group D2 than in group D1(all p <
      0.05). The time of awakening was significantly longer and the rates of
      respiratory depression were significantly higher in group D2 than in group D1
      (all p < 0.05) There were no significant differences in other parameters between
      both groups. CONCLUSION: Intranasal dexmedetomidine is a new, safe, and effective
      approach for gastroscopy because it has more stable respiratory and circulatory
      parameters and less adverse reactions than intravenous dexmedetomidine.

PMID- 24887338
TI  - ASAPS (American Society of Aesthetic Plastic Surgery)--2013 Annual Statistics.

PMID- 24887337
TI  - Evaluation of etanercept dose reduction in patients with rheumatoid arthritis
      using pharmacokinetic/pharmacodynamic modeling and simulation.
AB  - OBJECTIVES: In this study, we attempt to explore the feasibility of alternative
      dosing regimens of etanercept in patients with rheumatoid arthritis (RA) using
      pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulation. METHODS: All
      data used for estimation of PK/PD model parameters were collected from previously
      published literatures. American College of Rheumatology (ACR) 20/50/70 response
      rate and a disease activity score in 28 joints (DAS28) was selected as the
      principal clinical endpoint for further PK/PD modeling. The cumulative AUC (area
      under the concentration-time curve) of etanercept for different dosing regimens
      was calculated based on the final PK model and was then linked to the time course
      of clinical endpoints. Ten different dosing regimens were simulated in this
      study. RESULTS: The PK model that best fit the serum concentration-time data for
      etanercept was a one-compartment model with first order absorption and
      elimination. Based on the PK/PD analysis, the relationship between the predicted
      cumulative AUC of etanercept to the ACR 20/50/70 response rate and DAS28 score
      was well characterized by Emax logistic and inhibitory Emax model, respectively.
      In our simulations, the following dosing regimens that are equally effective to
      current recommended dosage of 25 mg twice weekly (b.i.w.): (1) 25 mg once weekly
      (q.w.); (2) 50 mg every 2 weeks (q2w); (3) 25 mg b.i.w. for 3 months and 25 mg
      q2w thereafter; and (4) 50 mg q.w. for 3 months and 50 mg q2w thereafter.
      CONCLUSION: In this study, the clinical data was well described by the models
      developed, and several alternative dosing regimens were proposed. Further
      clinical studies in patients are still needed to confirm our findings.

PMID- 24887340
TI  - Letter from the President of PSNCB.

PMID- 24887339
TI  - What is your story?

PMID- 24887341
TI  - Current approaches to free flap monitoring.
AB  - Postoperative monitoring of free flaps remains an essential component of care in
      patients undergoing microsurgical reconstructive surgery. Early recognition of
      vascular problems and prompt surgical intervention improve the chances for flap
      salvage. Physical examination remains the cornerstone of free flap monitoring,
      but more recently, additional technologies have been developed for this purpose.
      In this article, current approaches to free flap monitoring are reviewed. 

PMID- 24887343
TI  - Analysis of formal complaints in 1,645 liposuction operations.

PMID- 24887344
TI  - The "nuts & bolts" of becoming an aesthetic provider: part 3-maximizing your
      aesthetic practice and client outcomes.
AB  - The final installment of this 3-part series of articles on becoming an aesthetic
      provider centers on the steps necessary to maximize an aesthetic medical practice
      and tips for optimal client outcomes. We discuss the importance of education for
      the aesthetic provider, the staff, and the client, as well as how to create
      client loyalty. On the basis of years of experience, "pearls and pitfalls" are
      discussed, so the novice, intermediate, and advanced aesthetic providers can
      minimize mistakes and maximize their success in this exciting and growing
      profession. 

PMID- 24887345
TI  - Bullying in the health care environment.

PMID- 24887346
TI  - The role of the speech-language pathologist in maximizing the results of
      instrumental assessment of velopharyngeal function.

PMID- 24887347
TI  - Stop "cruising for a bruising": mitigating bruising in aesthetic medicine.
AB  - The quest to restore a more youthful appearance by filling and volumizing facial
      deformities and deficiencies continues to be an ongoing pursuit in the
      noninvasive aesthetics market. Bruising can result from the delivery of
      neuromodulators and dermal fillers--common tools in the aesthetic provider's
      armamentarium to combat the ravages of aging. There are steps both the aesthetic
      provider and the client can take to minimize the potential for bruising. This
      article focuses on the etiology of bruising, the pharmacological and herbal
      agents to avoid prior to an aesthetic procedure, techniques to utilize during
      aesthetic procedures that lessen the potential of bruise formation, and
      pharmacological and herbal agents to administer after an aesthetic procedure to
      ultimately mitigate bruise formation.

PMID- 24887349
TI  - Surgical options for lymphedema following breast cancer treatment.
AB  - Surgical options for treating lymphedema have expanded in recent years. For many
      years the only treatment options were conservative nonsurgical therapies and
      excisional surgeries. Advances in microsurgery have made it possible to
      reconstruct lymphatic function. Reconstructive surgical options include
      lymphaticovenular bypass, lymphaticolymphatic bypass, and vascularized lymph node
      transfer. Currently, there is no consensus on how or when to surgically treat
      lymphedema, and more studies are needed to evaluate the efficacy and risks of
      each of these techniques. 

PMID- 24887351
TI  - Simplified negative pressure wound therapy with instillation: advances and
      recommendations.
AB  - Positive results have been demonstrated with the adjunctive use of negative
      pressure wound therapy (NPWT) and instillation (NPWTi) for stalled and/or complex
      wounds. With these combined therapies, instillation assists in wound bed
      preparation and cleansing by loosening soluble material in the wound bed, which
      can be subsequently removed during the NPWT phase. Previously reported instilled
      solutions have included saline, topical cleansers, and antiseptics. Recently, a
      new NPWTi system (V.A.C. VeraFloTM Therapy, KCI USA, Inc., San Antonio, TX) has
      been introduced that includes automated, volumetrically controlled delivery of
      solutions and new foam dressings specifically designed for use with NPWTi. We
      present the latest NPWTi technologies, provide nursing recommendations for
      patient management, and conclude with a case study. 

PMID- 24887353
TI  - Should hysterectomy complement prophylactic salpingo-oophorectomy in BRCA1 and
      BRCA2 mutation carriers?

PMID- 24887352
TI  - Physiological and psychological responses of young males during spring-time walks
      in urban parks.
AB  - BACKGROUND: It is widely believed that contact with the natural environment can
      improve physical and mental health. Urban green spaces may provide city residents
      with these benefits; however, there is a lack of empirical field research on the
      health benefits of urban parks. METHODS: This field experiment was performed in
      May. Seventeen males aged 21.2 +/- 1.7 years (mean +/- standard deviation) were
      instructed to walk predetermined 15-minute courses in an urban park and a nearby
      city area (control). Heart rate and heart rate variability (HRV) were measured to
      assess physiological responses. The semantic differential (SD) method, Profile of
      Mood States (POMS), and State-Trait Anxiety Inventory (STAI) were used to measure
      psychological responses. RESULTS: Heart rate was significantly lower while
      walking in the urban park than while walking in the city street. Furthermore, the
      urban park walk led to higher parasympathetic nervous activity and lower
      sympathetic nervous activity compared with the walk through the city street.
      Subjective evaluations were generally in accordance with physiological reactions,
      and significantly higher scores were observed for the 'comfortable', 'natural',
      and 'relaxed' parameters following the urban park walk. After the urban park
      walk, the score for the 'vigor' subscale of the POMS was significantly higher,
      whereas that for negative feelings such as 'tension-anxiety' and 'fatigue' was
      significantly lower. The score for the anxiety dimension of the STAI was also
      significantly lower after the urban park walk. CONCLUSIONS: Physiological and
      psychological results from this field experiment provide evidence for the
      physiological and psychological benefits of urban green spaces. A brief spring
      time walk in an urban park shifted sympathetic/parasympathetic balance and
      improved mood state.

PMID- 24887354
TI  - Physician pain and discomfort during minimally invasive gynecologic cancer
      surgery.
AB  - OBJECTIVE: Despite increasing awareness of physical strain to surgeons associated
      with minimally invasive surgery (MIS), its use continues to expand. We sought to
      gather information from gynecologic oncologists regarding physical discomfort due
      to MIS. METHODS: Anonymous surveys were e-mailed to 1279 Society of Gynecologic
      Oncology (SGO) members. Physical symptoms (numbness, pain, stiffness, and
      fatigue) and surgical and demographic factors were assessed. Univariate and
      multivariate analyses were performed to determine risk factors for physical
      symptoms. RESULTS: We analyzed responses of 350 SGO members who completed the
      survey and currently performed >50% of procedures robotically (n=122),
      laparoscopically (n=67), or abdominally (n=61). Sixty-one percent of members
      reported physical symptoms related to MIS. The rate of symptoms was higher in the
      robotic group (72%) than the laparoscopic (57%) or abdominal groups (49%)
      (p=0.0052). Stiffness (p=0.0373) and fatigue (p=0.0125) were more common in the
      robotic group. Female sex (p<0.0001), higher caseload (p=0.0007), and academic
      practice (p=0.0186) were associated with increased symptoms. On multivariate
      analysis, robotic surgery (odds ratio [OR] 2.38, 95% CI 1.20-4.69) and female sex
      (OR 4.20, 95% CI 2.13-8.29) were significant predictors of symptoms. There was no
      correlation between seeking treatment and surgical modality (laparotomy 11%,
      robotic 20%, laparoscopy 25%, p=0.12). CONCLUSIONS: Gynecologic oncologists
      report physical symptoms due to MIS at an alarming rate. Robotic surgery and
      female sex appear to be risk factors for physical discomfort. As we strive to
      improve patient outcomes and decrease patient morbidity with MIS, we must also
      work to improve the ergonomics of MIS for surgeons.

PMID- 24887355
TI  - Assessment of palliative care training in gynecologic oncology: a gynecologic
      oncology fellow research network study.
AB  - OBJECTIVE: Palliative care is recognized as an important component of oncologic
      care. We sought to assess the quality/quantity of palliative care education in
      gynecologic oncology fellowship. METHODS: A self-administered on-line
      questionnaire was distributed to current gynecologic oncology fellow and
      candidate members during the 2013 academic year. Descriptive statistics,
      bivariate and multivariate analyses were performed. RESULTS: Of 201 fellow and
      candidate members, 74.1% (n=149) responded. Respondents were primarily women
      (75%) and white (76%). Only 11% of respondents participated in a palliative care
      rotation. Respondents rated the overall quality of teaching received on
      management of ovarian cancer significantly higher than management of patients at
      end of life (EOL), independent of level of training (8.25 vs. 6.23; p<0.0005).
      Forty-six percent reported never being observed discussing transition of care
      from curative to palliative with a patient, and 56% never received feedback about
      technique regarding discussions on EOL care. When asked to recall their most
      recent patient who had died, 83% reported enrollment in hospice within 4 weeks of
      death. Fellows reporting higher quality EOL education were significantly more
      likely to feel prepared to care for patients at EOL (p<0.0005). Mean ranking of
      preparedness increased with the number of times a fellow reported discussing
      changing goals from curative to palliative and the number of times he/she
      received feedback from an attending (p<0.0005). CONCLUSIONS: Gynecologic oncology
      fellow/candidate members reported insufficient palliative care education. Those
      respondents reporting higher quality EOL training felt more prepared to care for
      dying patients and to address complications commonly encountered in this setting.

PMID- 24887357
TI  - Morphological, diagnostic and surgical features of ectopic thyroid gland: a
      review of literature.
AB  - Ectopic thyroid tissue remains a rare developmental abnormality involving
      defective or aberrant embryogenesis of the thyroid gland during its passage from
      the floor of the primitive foregut to its usual final position in pre-tracheal
      region of the neck. Its specific prevalence accounts about 1 case per 100.000
      300.000 persons and one in 4.000-8.000 patients with thyroid disease show this
      condition. The cause of this defect is not fully known. Despite genetic factors
      have been associated with thyroid gland morphogenesis and differentiation, just
      recently some mutation has been associated with human thyroid ectopy. Lingual
      region in the most common site of thyroid ectopy but ectopic thyroid tissue were
      found in other head and neck locations. Nevertheless, aberrant ectopic thyroid
      tissue has been found in other places distant from the neck region. Ectopic
      tissue is affected by different pathological changes that occur in the normal
      eutopic thyroid. Patients may present insidiously or as an emergency. Diagnostic
      management of thyroid ectopy is performed by radionuclide thyroid imaging,
      ultrasonography, CT scan, MRI, biopsy and thyroid function tests. Asymptomatic
      euthyroid patients with ectopic thyroid do not usually require therapy but are
      kept under observation. For those with symptoms, treatment depends on size of the
      gland, nature of symptoms, thyroid function status and histological findings.
      Surgical excision is often required as treatment for this condition. 

PMID- 24887358
TI  - Day case appendectomy in adults: a review.
AB  - BACKGROUND: Day-case appendectomy (DCA) for acute appendicitis has been suggested
      as a valuable alternative to traditional appendectomy but many surgeons are
      reluctant to apply this technique in adults. The aim of the present review is to
      discuss the feasibility of DCA in adults. METHODS: Three reviewers independently
      searched the Pubmed and Embase databases for articles on DCA. They then
      considered the criteria applicable to the surgery, day-case surgery, time taken
      for patients to resume normal activities, mean time to resumption of work and
      patient satisfaction. RESULTS: Between 1993 and 2012, 13 studies (with
      retrospective (n = 8), prospective (n = 4) or case-control study (n = 1) designs)
      dealt with DCA. A total of 1152 adults underwent DCA. 312 patients (27.08%) were
      discharged within 12 h, 614 (53.29%) within 24 h and 242 (21.01%) within 72 h.
      CONCLUSION: The few data reported in 13 studies, suggest that DCA may be
      feasible. However prospective studies are needed before DCA can be recommended.

PMID- 24887356
TI  - Proof by synthesis of Tobacco mosaic virus.
AB  - BACKGROUND: Synthetic biology is a discipline that includes making life forms
      artificially from chemicals. Here, a DNA molecule was enzymatically synthesized
      in vitro from DNA templates made from oligonucleotides representing the text of
      the first Tobacco mosaic virus (TMV) sequence elucidated in 1982. No infectious
      DNA molecule of that seminal reference sequence exists, so the goal was to
      synthesize it and then build viral chimeras. RESULTS: RNA was transcribed from
      synthetic DNA and encapsidated with capsid protein in vitro to make synthetic
      virions. Plants inoculated with the virions did not develop symptoms. When two
      nucleotide mutations present in the original sequence, but not present in most
      other TMV sequences in GenBank, were altered to reflect the consensus, the
      derivative synthetic virions produced classic TMV symptoms. Chimeras were then
      made by exchanging TMV capsid protein DNA with Tomato mosaic virus (ToMV) and
      Barley stripe mosaic virus (BSMV) capsid protein DNA. Virus expressing ToMV
      capsid protein exhibited altered, ToMV-like symptoms in Nicotiana sylvestris. A
      hybrid ORF6 protein unknown to nature, created by substituting the capsid protein
      genes in the virus, was found to be a major symptom determinant in Nicotiana
      benthamiana. Virus expressing BSMV capsid protein did not have an extended host
      range to barley, but did produce novel symptoms in N. benthamiana. CONCLUSIONS:
      This first report of the chemical synthesis and artificial assembly of a plant
      virus corrects a long-standing error in the TMV reference genome sequence and
      reveals that unnatural hybrid virus proteins can alter symptoms unexpectedly.

PMID- 24887360
TI  - Curing behaviour of high-viscosity bulk-fill composites.
AB  - OBJECTIVES: This study aimed to assess the effect of curing conditions--exposure
      time, mode, energy density, and exposure distance--on the mechanical properties
      of high-viscosity bulk-fill resin-based composites (RBCs) measured at simulated
      clinical relevant filling depths. METHODS: Three high-viscosity bulk-fill RBCs
      were investigated by assessing the variation in micromechanical properties in
      200MUm steps (Vickers hardness [HV] and indentation modulus [E]) within simulated
      6-mm deep fillings (n=5) polymerized under 16 different curing conditions. The
      exposure duration was 5, 20, and 40s in the standard power mode; 3, 4, and 8s in
      the high power mode; and 3 and 6s in the plasma mode; the exposure distance was 0
      and 7mm. Energy density ranged from 2.63 to 47.03J/cm(2). Measurements were
      performed after 24h of storage in distilled water at 37 degrees C. The depth of
      cure (DOC) was calculated as the 80% hardness drop-off. RESULTS: The results were
      compared using one- and multiple-way ANOVAs and Tukey's HSD post hoc test
      (alpha=0.05). The effect of the parameter material was significant and strong on
      all measured properties (p<0.05, partial eta-squared etaP(2)=0.492 for E, 0.562
      for HV, and 0.087 for DOC). Energy density exerted the strongest influence on the
      measured properties in all materials, whereas the influence of the exposure
      distance was strong on DOC, low on E and not significant on HV. The high
      viscosity bulk-fill RBCs respond heterogeneously to variations in curing
      conditions. CONCLUSIONS: A lower energy density limit was identified, allowing
      for a 4mm material bulk placement (5.88J/cm(2) for EvoCeram Bulk Fill, 7.0J/cm(2)
      for x-tra fil, and 23.51J/cm(2) for SonicFill). This limit increased to
      47.03J/cm(2) for a 5mm bulk placement, as claimed for SonicFill. To maintain
      mechanical properties in depth, however, an energy density of at least
      23.51J/cm(2) is recommended for EvoCeram Bulk Fill and x-tra fil and 47.03J/cm(2)
      for SonicFill, respectively. This energy density should be achieved at moderate
      irradiance and increased curing time. CLINICAL SIGNIFICANCE: An exposure time of
      20s at moderate irradiance is recommended for all materials for a 4 mm bulk
      placement.

PMID- 24887359
TI  - Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict
      benefit of intensified carboplatin-based chemotherapy.
AB  - INTRODUCTION: BRCA-mutated breast cancer cells lack the DNA-repair mechanism
      homologous recombination that is required for error-free DNA double-strand break
      (DSB) repair. Homologous recombination deficiency (HRD) may cause
      hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating
      agents and platinum salts. HRD can be caused by BRCA mutations, and by other
      mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast
      cancers as these resemble BRCA1-mutated breast cancer closely and might also
      share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated,
      estrogen receptor (ER)-positive breast cancers have remained elusive. The current
      study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated
      breast cancers can identify breast cancer patients with TN as well as ER
      positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing
      chemotherapy. METHODS: Array comparative genomic hybridization (aCGH) was used to
      classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1
      and/or BRCA2-mutated breast cancers were defined as having a BRCA-likeCGH
      status, others as non-BCRA-likeCGH. Stage-III patients (n = 249) had participated
      in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide
      thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide
      (FE90C) chemotherapy. RESULTS: Among patients with BRCA-likeCGH tumors (81/249,
      32%), a significant benefit of HD-CTC compared to FE90C was observed regarding
      overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not
      seen for patients with non-BRCA-likeCGH tumors (adjusted hazard ratio 0.90, 95%
      CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-likeCGH tumors were ER-positive.
      CONCLUSIONS: Distinct aCGH patterns differentiated between HER2-negative patients
      with a markedly improved outcome after adjuvant treatment with an intensified DNA
      DSB-inducing regimen (BRCA-likeCGH patients) and those without benefit (non-BRCA
      likeCGH patients).

PMID- 24887361
TI  - Radiation therapy alters microhardness and microstructure of enamel and dentin of
      permanent human teeth.
AB  - OBJECTIVES: To evaluate, in vitro, the effects of ionizing radiation on the
      mechanical and micro-morphological properties of enamel and dentin of permanent
      teeth. METHODS: Enamel and dentin microhardness (n=12 hemi-sections) was
      evaluated at three depths (superficial, middle and deep) prior to (control) and
      after every 10Gy radiation dose up to a cumulative dose of 60Gy by means of
      longitudinal microhardness. Data were analyzed using two-way analysis of variance
      and Tukey's test at a significance level of 5%. Enamel and dentin morphology was
      assessed by scanning electron microscopy (SEM) for semi-quantitative analysis
      (n=8 hemi-sections). Data were analyzed using Kruskal-Wallis and Dunn's or Fisher
      exact tests at a significance level of 5%. RESULTS: The application of ionizing
      radiation did not change the overall enamel microhardness, although an increase
      in superficial enamel microhardness was observed. The micro-morphological
      analysis of enamel revealed that irradiation did not influence rod structure but
      interprismatic structure became more evident. Dentin microhardness decreased
      after 10, 20, 30, 50 and 60Gy cumulative doses (p<0.05) compared with non
      irradiated dentin, mainly in the middle portion of the tissue. The micro
      morphological analysis revealed fissures in the dentin structure, obliterated
      dentinal tubules and fragmentation of collagen fibers after 30 and 60Gy
      cumulative doses. CONCLUSIONS: Although ionizing radiation did not affect the
      enamel microhardness of permanent teeth as a whole, an increase in superficial
      enamel microhardness was observed. Dentin microhardness decreased after almost
      all radiation doses compared with the control, with the greatest reduction of
      microhardness in the middle depth region. The morphological alterations on enamel
      and dentin structures increased with the increase of the radiation dose, with a
      more evident interprismatic portion, presence of fissures and obliterated
      dentinal tubules, and progressive fragmentation of the collagen fibers. CLINICAL
      SIGNIFICANCE: This study shows that irradiation affects microhardness and micro
      morphology of enamel and dentin of permanent teeth. The effects of gamma
      irradiation on dental substrate might contribute to increased risk of radiation
      tooth decay associated with salivary changes, microbiota shift and high soft and
      carbohydrate-rich food intake.

PMID- 24887362
TI  - Does dental disease presence equate to treatment need among care home residents?
AB  - OBJECTIVES: This study aimed to explore the relationship between dental disease,
      complexity and dental treatment needs of care home residents. METHODS: Survey of
      residents in care homes in Wales. Random sample of participants from a random
      selection of care homes across Wales, UK. Data collection involved questionnaires
      and dental examinations. RESULTS: Data were collected from 655 care home
      residents in 213 care homes. Half of all residents reported good or very good
      oral health but most had dental treatment needs. 73% of dentate residents had
      active caries, of those, 53% required restorations and 37% needed extractions.
      All were deemed to require dental examination. 60% of dentate residents and 50%
      of edentate residents had case complexity, which influenced the delivery of care.
      CONCLUSIONS: There is significant unmet dental treatment need amongst care home
      residents. Dental disease presence alone is a poor indicator of the need for care
      and does not account for case complexity or the shift towards a patient centred
      rather than disease focussed approach to care. Measures for treatment needs and
      complexity are required when undertaking assessments of oral health needs in care
      homes. CLINICAL SIGNIFICANCE: Traditional oral health surveys measuring dental
      disease do not necessarily equate to treatments required for care home residents
      and do not reflect the complexity and difficulties involved in delivering dental
      care. This survey highlights dental needs in care homes, and the difficulties
      involved in delivering care to address these needs.

PMID- 24887364
TI  - [DSM-5: lights and shadows].

PMID- 24887363
TI  - [Still the social factor: crisis in the clinical practice].
AB  - Consultations in our hospital center are problematic, mainly due to the poor
      living situation which patients come from (the suburbs of Buenos Aires). The
      housing situation, the environment and the economic or political conditions of
      these patients frame "the social" emergency that sets the context and the impact
      in the different psychopathological symptoms that they present. These conditions
      should also be reviewed from our theoretical assessment together with the
      clinical approach that our assistance practice studies. From a perception
      viewpoint we observe that "self-perception is far from any ideals. The perception
      of their environment is threatening and has no future". We constantly note the
      loss of the value of words and speech, when we hear our patients, wo have turned
      language into just an abject joy, as in the word of the addict. These issues must
      be studied from a theoretical point of view to be applied clinically. Such
      analysis reveals that our practice takes place in a context of failure. However,
      we cannot move backwards in "potential treatment" as Lacan states in the ethics
      as regards psychosis.

PMID- 24887365
TI  - [An approach to DSM-5: a breakthrough in psychiatry?].
AB  - One of the main problems of current psychiatry is that its diagnostic
      classification systems are not precise and reliable, they do not help to identify
      with certainty a specific type of mental disorder and they frequently overlap two
      or more diagnoses. This may conduce to over diagnosis and overtreatment, which is
      the main criticism of the DSM system. The American Psychiatric Association (APA)
      launched recently the DSM-5, the fifth edition of its diagnostic manual, which
      provides diagnostic criteria for thousands of psychiatrist, psychologist and
      researchers and who will be using it in the next coming years. DSM-5, like the
      preceding editions, placed disorders in discrete categories such as bipolar
      disorder or schizophrenia. The problem is that scientists have been unable to
      find yet a genetic or neurobiological evidence to support the theory of mental
      disorders as separate categories. Several authors wanted the latest DSM to move
      away from the category model towards a new "dimensional approach", where
      disorders can be measured and mental illnesses overlapping can be reduced. Recent
      findings supports this new dimensional strategy, suggesting that the disorders
      are a product of shared risk factors that lead to abnormalities in specific
      drives, which can be measured and used to place persons on one of several
      spectra. In some parts the DSM-5 entered changes aiming to achieve a greater
      objectivity. The door for new changes in each category, dimension or criteria has
      been opened, favoring an evidence-based development of the future versions. DSM-5
      is presented as a "living document" that can be updated easily. However, the
      category model still remains for many disorders. The future research in
      psychiatric diagnostic systems requires more genetic-molecular and
      neurophysiological evidence and more objective multinational field trials, in
      order to confirm the existence of the new diagnostic entities, spectrums or
      dimensions. This approach may provide us reliable information about the
      pathogenesis, psychopathology, adequate taxonomy and treatment of mental
      disorders. 

PMID- 24887366
TI  - [Research Domain Criteria (RDoC). Political framework and content].
AB  - The Research Domain Criteria (RDoC) is an initiative of the National Institute of
      Mental Health of the United States of America, which based on research purposes
      consists of a new way of classifying mental disorders. His raison d'etre is based
      on the conclusion that the knowledge progress of neurosciences does not seem to
      confirm the validity of the conventional psychiatric diagnoses. Furthermore,
      researching based on such diagnoses would weaken the progress in Psychiatry.
      Besides these scientific reasons, the Research Domain Criteria project is born
      within a political framework, giving raise to economic tensions. The objective of
      this paper is to discuss the first issue without avoiding the second one. 

PMID- 24887367
TI  - [Intellectual disability: is the new denomination a shift in perspective?].
AB  - The change from "mental retardation" to "intellectual disability" (ID) in the new
      version of the DSM-5 aims not only to eliminate stigmatization but also to modify
      diagnostic criteria. The IQ is no longer preeminent for defining ID or its
      severity, relying instead on broader clinical criteria and neuropsychological
      evaluation. More relevance is given to the evaluation of the individual's
      performance on daily life. This perspective addresses the concerns raised since
      the 1990's by organizations representing professionals and patients and their
      families. To better understand these changes we reviewed the definitions and
      criteria of previous DSM editions. The adoption of the alternative denomination
      of the "intellectual developmental disorder" is compatible with the ICD-11 to be
      released in 2015. This guideline was based on the recommendation of the working
      group for the classification of the intellectual disabilities. 

PMID- 24887368
TI  - [Schizophrenia according to DSM-5].
AB  - The system of classification of psychiatric disorders has evolved during the last
      half-century. This article briefly reviews the modifications of the structure of
      the chapter "Schizophrenia spectrum and other psychotic disorders" in DSM-5; then
      analyzes in detail the changes that were specifically made for schizophrenia.
      Among them, the fundamentals are: a) the elimination of the special treatment of
      bizarre delusions and hallucinations of Schneiderian "first rank", b) the
      clarification of the definition of negative symptoms, and c) the addition of the
      requirement that at least one of the two required characteristic symptoms should
      be disorganized speech, hallucinations or delusions. It also discusses the
      elimination of subtypes of schizophrenia and the addition of psychopathological
      dimensions, and the consequences of the lack of validated biomarkers that could
      facilitate the diagnosis. 

PMID- 24887369
TI  - [Historical and conceptual evolution of non-schizophrenic psychotic disorders in
      DSM].
AB  - After firmly established the "kraepelinean dichotomy" (dementia praecox - manic
      depressive insanity), classical psychiatry began to describe a group of psychotic
      disorders which did not fit in any of these main diagnoses. Many of these
      clinical pictures where incorporated to the DSM and underwent several changes
      throughout the successive editions of the American manual. This article aims to
      make a historical and conceptual overview of this group of non-schizophrenic
      psychotic disorders accompanying schizophrenia in the "Schizophrenia spectrum and
      other psychotic disorders" chapter of DSM-5. 

PMID- 24887370
TI  - [Bipolar disorder and DSM-5: still far from the disease].
AB  - Although bipolar disorder is highly disabling, data from different regions of the
      world agree on the finding that there is a prolonged diagnostic delay in affected
      people. Among the main factors that could explain this phenomenon are
      contemporary conceptualizations of bipolar disorder and diagnostic criteria of
      the DSM-IV. Moreover, in recent years it has been cautioned about the risk of
      overdiagnosis of this disorder. In this context, the new edition of the DSM is
      presented. The modifications included in the DSM-5 regarding the diagnosis of
      bipolar disorder are described in this paper. Likewise, the practical
      implications of these changes are discussed. 

PMID- 24887371
TI  - [Anxiety disorders in DSM-5].
AB  - The fifth edition of Diagnostic and Statistical Manual, the DSM-5 appeared
      officially in May 2013 during the development of the 166th Annual Meetingof the
      American Psychiatric Association (APA) in San Francisco. The drafting process was
      long and complex; much of the debate became public so that the expectations were
      great. And it must be said that the new edition did not disappoint, as many
      changes were made in relation to their predecessors. In Chapter of Anxiety
      Disorders, which is reviewed in this article, the changes were significant.
      Obsessive-compulsive disorder and Stress-related disorders were excluded and new
      clinical pictures, such as separation anxiety disorder and selective mutism, were
      included. And took place was the long awaited split between panic disorder and
      agoraphobia, now two separate disorders. 

PMID- 24887372
TI  - [DSM-5: OCD and related disorders].
AB  - DSM-5 moved OCD out from under the Anxiety Disorder section, into a new category:
      Obsessive Compulsive and Related Disorders and added two new specifiers.
      Specifically a modification of one specifier (insight) and the addition of a new
      tic specifier. DSM-5 redefined obsessions and recognizes the importance of
      avoidance and thought stopping beyond compulsions as other strategies to deal
      with obsessions. OCD related disorders include: Trichotillomania, Hoarding
      Disorder, Skin Picking Disorder, and Body Dysmorphic Disorder. 

PMID- 24887373
TI  - [Posttraumatic stress disorder: meaningful changes in DSM-5].
AB  - The fact that posttraumatic stress disorder is a very important construct in
      public health and opinion, especially in the United States of America, has veiled
      it dubious specificity and problematic universality. HYPOTHESIS: the abandon of
      Freudian theory since 1980 was correlative of a permanent revision of criteria to
      define "traumatic" in DSM versions, as well as of revaluation of ancient theory
      of dissociation. METHOD: most meaningful changes introduced in PTSD criteria are
      critically reviewed from DSM-IV to DSM-5. "Traumatic", symptoms and dissociative
      estates, and a new preschool children subtype are revised. CONCLUSION:
      "Traumatic" yet being an artificial criterion is steel needed in order to keep
      the construct as a whole. Dissociative estates occupy an important place for the
      American authors and have turned more visible in DSM-5 than in previous DSM. New
      chapter "Trauma and stressor disorders" and new descriptions about PTSD support
      an enlarged clinical view of "traumatic". Inconsistencies found between reviews
      considered for PTSD in DSM-5 show that different work groups contribute to the
      construction of the disorder with fragmentary and divorced parts from one
      another.

PMID- 24887374
TI  - [Classifications in psychiatry: from Praxeos Medicae to DSM-I].

PMID- 24887376
TI  - Defective apoptosis in intestinal and mesenteric adipose tissue of Crohn's
      disease patients.
AB  - BACKGROUND: Crohn's disease (CD) is associated with complex pathogenic pathways
      involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue
      (MAT) has been associated with CD ethiopathology, since adipose thickening is
      detected close to the affected intestinal area. However, the potential role of
      altered apoptosis in MAT of CD has not been addressed. AIMS: To evaluate
      apoptosis in the intestinal mucosa and MAT of patients with CD. METHODS: Samples
      of intestinal mucosa and MAT from patients with ileocecal CD and from non
      inflammatory bowel diseases patients (controls) were studied. Apoptosis was
      assessed by TUNEL assay and correlated with the adipocytes histological
      morphometric analysis. The transcriptional and protein analysis of selected genes
      and proteins related to apoptosis were determined. RESULTS: TUNEL assay showed
      fewer apoptotic cells in CD, when compared to the control groups, both in the
      intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL)
      correlated significantly with the area and perimeter of the adipose cells in MAT.
      Transcriptomic and proteomic analysis reveal a significantly lower transcript and
      protein levels of Bax in the intestinal mucosa of CD, compared to the controls;
      low protein levels of Bax were found localized in the lamina propria and not in
      the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level
      of Caspase 3 were seen in the MAT of CD patients. CONCLUSION: The defective
      apoptosis in MAT may explain the singular morphological characteristics of this
      tissue in CD, which may be implicated in the pathophysiology of the disease.

PMID- 24887377
TI  - Site-specific bioconjugation of a murine dihydrofolate reductase enzyme by
      copper(I)-catalyzed azide-alkyne cycloaddition with retained activity.
AB  - Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is an efficient reaction
      linking an azido and an alkynyl group in the presence of copper catalyst.
      Incorporation of a non-natural amino acid (NAA) containing either an azido or an
      alkynyl group into a protein allows site-specific bioconjugation in mild
      conditions via CuAAC. Despite its great potential, bioconjugation of an enzyme
      has been hampered by several issues including low yield, poor solubility of a
      ligand, and protein structural/functional perturbation by CuAAC components. In
      the present study, we incorporated an alkyne-bearing NAA into an enzyme, murine
      dihydrofolate reductase (mDHFR), in high cell density cultivation of Escherichia
      coli, and performed CuAAC conjugation with fluorescent azide dyes to evaluate
      enzyme compatibility of various CuAAC conditions comprising combination of
      commercially available Cu(I)-chelating ligands and reductants. The condensed
      culture improves the protein yield 19-fold based on the same amount of non
      natural amino acid, and the enzyme incubation under the optimized reaction
      condition did not lead to any activity loss but allowed a fast and high-yield
      bioconjugation. Using the established conditions, a biotin-azide spacer was
      efficiently conjugated to mDHFR with retained activity leading to the site
      specific immobilization of the biotin-conjugated mDHFR on a streptavidin-coated
      plate. These results demonstrate that the combination of reactive non-natural
      amino acid incorporation and the optimized CuAAC can be used to bioconjugate
      enzymes with retained enzymatic activity. 

PMID- 24887379
TI  - Clinical outcomes of AML patients relapsing after matched-related donor and
      umbilical cord blood transplantation.
AB  - AML relapse remains the leading cause of transplant failure among Allo-SCT
      recipients. A single institution study was conducted on 348 patients with AML who
      received an Allo-SCT from an umbilical cord blood (UCB, 222) or HLA-matched
      related (RD, 126) donor between 2000-2011. Relapse after Allo-SCT occurred in 72
      UCB and 32 RD transplant recipients. Three patients achieved CR after withdrawal
      of immune suppression with no further therapy. Fifty-two patients received
      intensive post-relapse therapy, defined as systemic chemotherapy (22 UCB, 7 RD),
      second Allo-SCT (nine UCB, two RD), or DLI+/-systemic chemotherapy (0 UCB, 12
      RD); of these, 25% achieved CR (21% UCB vs 35% RD, P=0.16). Survival at 1 year
      after relapse was 22% for all patients (19% UCB vs 28% RD, P=0.36). In
      multivariable analysis, post-relapse mortality was lower in patients receiving
      intensive therapy for relapse (hazard ratio (HR)=0.4; 95% confidence interval
      (CI) 0.2-0.6, P<0.01) and higher in patients with peripheral blood blasts above
      the median (HR=3.8; 95% CI 2.2-6.6, P<0.01), active infection (HR=1.9; 95% CI 1.0
      3.5, P=0.05) and non-infectious medical complications (HR=2.0; 95% CI 1.2-3.5,
      P=0.01). In conclusion, patients with AML relapsing after Allo-SCT who were in
      good-enough clinical condition to receive intensive therapy had superior short
      term survival.

PMID- 24887380
TI  - Lomustine use in combination with etoposide, cytarabine and melphalan in a brief
      conditioning regimen for auto-HSCT in patients with lymphoma: the optimal dose.

PMID- 24887378
TI  - Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective
      analysis with 14-year follow-up.
AB  - Optimal treatment approach continues to remain a challenge for systemic light
      chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with
      long-term survival. However, failure to show survival benefit in randomized study
      raises questions regarding its efficacy. We present a comparative outcome
      analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over
      a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto
      SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%.
      Novel agents were used as part of induction therapy in 56% of transplant
      recipients vs 46% of CTR patients. Hematological and organ responses were seen in
      74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively.
      The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively.
      Landmark analysis of patients alive at 1-year after diagnosis showed improved 5
      year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis,
      age <60 years, induction therapy with novel agents, kidney only involvement and
      Auto-SCT were associated with improved survival. In conclusion, Auto-SCT is
      associated with long-term survival for patients with AL amyloidosis.

PMID- 24887381
TI  - Umbilical cord blood transplantation and unmanipulated haploidentical
      hematopoietic SCT for pediatric hematologic malignances.
AB  - This study aimed to compare the therapeutic effects of single umbilical cord
      blood transplantation (UCBT) and unmanipulated haploidentical hematopoietic SCT
      (haplo-HSCT) in childhood hematologic malignances. We enrolled 410 consecutive
      children who received either single UCBT (n=37) or haplo-HSCT from a family donor
      (n=373) during the same time period. For each UCBT recipient, three recipients
      matched for year of HSCT, underlying diseases, disease status and the length of
      follow-up were randomly selected from the haplo-HSCT cohort. Hematopoietic
      recovery was significantly faster in haplo-HSCT recipients than in UCBT
      recipients. The incidence of chronic GVHD was significantly higher in haplo-HSCT
      recipients. The incidence of CMV-related interstitial pneumonia was higher in
      UCBT recipients. The haplo-HSCT recipients had better 1-year OS (73.0% vs 56.8%,
      P=0.048), lower 1-year non-relapse mortality (NRM, 18.0% vs 35.1%, P=0.026) and
      lower 2-year NRM rates (19.9% vs 35.1%, P=0.044). The relapse- and disease-free
      survival rates did not differ significantly between the groups. Our results
      showed that compared with UCBT, unmanipulated haplo-HSCT can improve the outcomes
      of children with hematologic malignances.

PMID- 24887382
TI  - Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor
      or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I
      clinical trial.
AB  - The safety, kinetics and efficacy of plerixafor+pegfilgrastim for hematopoietic
      stem and progenitor cell (HSPC) mobilization are poorly understood. We treated 12
      study patients (SP; lymphoma n=10 or myeloma n=2) with pegfilgrastim (6 mg SC
      stat D1) and plerixafor (0.24 mg/kg SC nocte from D3). Six SP were 'predicted
      poor-mobilizers' and six were 'predicted adequate-mobilizers'. Peripheral blood
      (PB) CD34(+) monitoring commenced on D3. Apheresis commenced on D4. Comparison
      was with 22 historical controls (HC; lymphoma n=18, myeloma n=4; poor mobilizers
      n=4), mobilized with pegfilgrastim alone. Eight (67%) SP had PB CD34(+) count ?5
      * 10(6)/L D3 post pegfilgrastim; all SP surpassed this threshold the morning
      after plerixafor. In SP, PBCD34(+) counts peaked D4 6/12 (50%), remaining ?5 *
      10(6)/L for 4 days in 8/12 (67%). All SP successfully yielded target cell numbers
      (?2 * 10(6)/kg) within four aphereses. After maximum four aphereses, median total
      CD34+ yield was higher in SP than HC; 8.0 (range 2.4-12.9) vs 4.8 (0.4-14.0) *
      10(6)/kg (P=0.04). Seven of twelve (58%) SP achieved target yield after one
      apheresis. Flow cytometry revealed no tumor cells in PB or apheresis product of
      SP. Plerixafor+pegfilgrastim was well tolerated with bone pain (n=2), diarrhoea
      (n=2) and facial paraesthesiae (n=3). Plerixafor+pegfilgrastim is a simple, safe
      and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and
      good mobilizers, and is superior to pegfilgrastim alone.

PMID- 24887384
TI  - BEAM-conditioned autologous SCT improves the quality of response in Waldenstrom's
      macroglobulinaemia and lymphoplasmacytic lymphoma: a single centre's 10-year
      experience.

PMID- 24887385
TI  - Automated washing of autologous hematopoietic stem cell grafts after thawing does
      not impair engraftment.

PMID- 24887383
TI  - Autoimmune cytopenias after umbilical cord blood transplantation in adults with
      hematological malignancies: a single-center experience.
AB  - We describe incidence, clinical features, serological data, response to therapy
      and outcome of autoimmune cytopenias (ACs), including autoimmune hemolytic anemia
      (AIHA) and autoimmune thrombocytopenia (AIT) in a series of 281 consecutive
      adults with hematological malignancies that received single-unit umbilical cord
      blood transplantation (UCBT) at a single institution. AIHA was diagnosed in 15
      patients at a median time of 181 days (range, 25-543), 12 of them had cold
      antibodies (IgM). The 3-year cumulative incidence (CI) of AIHA was 5.4% (CI 95%
      2.7-8.1). Concomitant infections at the time of AIHA were present in 10 patients.
      Five out of nine patients that received corticosteroids achieved either a PR or a
      CR, whereas six out of eight patients that received rituximab responded. Four
      patients developed AIT giving a 3-year CI of 1.4% (CI 95% 0-2.8), concomitant
      infections were present in three of them. Multivariable analysis showed that
      development of chronic GVHD (relative risk (RR) 4; 95% CI 1.1-13.7; P=0.03) and
      diagnosis of CML (RR 4.3; 95% CI 1.5-12.7; P=0.008) were associated with an
      increased risk of AC. In conclusion, AIHA and AIT are relevant and clinically
      significant complications in UCBT recipients, especially among those that develop
      chronic GVHD. Response to therapy is sub-optimal, and rituximab should be
      considered as a therapeutic option, in this setting were most patients had cold
      AIHA and a serological profile similar to that seen in cold agglutinin disease. 

PMID- 24887386
TI  - An unusual case of B-ALL occurring in a patient with acute promyelocytic leukemia
      in remission after two hematopoietic SCTs: whose are the leukemic cells?

PMID- 24887387
TI  - Caregivers' quality of life after blood and marrow transplantation: a qualitative
      study.

PMID- 24887388
TI  - Juvenile arthritis after haematopoietic stem cell transplantation.

PMID- 24887389
TI  - Extracorporeal photopheresis for treatment of adults and children with acute
      GVHD: UK consensus statement and review of published literature.
AB  - Extracorporeal photopheresis (ECP) has been used for over 20 years to treat acute
      GVHD (aGVHD) and chronic GVHD. Evidence on the efficacy of response in aGVHD has
      continued to accrue and data suggest that there is a good response and prolonged
      survival in both children and adults with grade II-IV aGVHD. Unlike chronic GVHD
      where treatment schedules are typically one or two times monthly for 12-18
      months, patients with aGVHD respond rapidly to an intense weekly treatment
      schedule for 8 weeks, typically allowing steroids to be discontinued without
      flare-ups of aGVHD. Maintenance ECP therapy is generally not required. Many
      centres across Europe and United States treat aGVHD with ECP as second-line
      therapy and responses are excellent in a subset of patients. Unlike other second
      line therapies, ECP is not immunosuppressive and has no reported drug
      interactions. Importantly, ECP does not have a negative impact on the graft
      versus-malignancy effect of the transplant. This statement aims to select those
      patients most likely to respond to treatment and summarises treatment and
      monitoring schedules for the management of aGVHD in adult and paediatric patients
      to ensure the correct patients are treated with the optimal protocol for
      efficacy. 

PMID- 24887390
TI  - Exploring the multiple-level hypothesis of AoA effects in spoken and written
      object naming using a topographic ERP analysis.
AB  - Here we tested the multiple-loci hypothesis of age-of-acquisition effects in both
      spoken and handwritten object naming using Event-Related Potentials (ERPs) and
      spatiotemporal segmentation analysis. Participants had to say aloud or write down
      picture names that varied on frequency trajectory (age-of-acquisition). Early
      acquired words yielded shorter naming times than late-acquired words in both
      spoken and written naming. More importantly, AoA modulated ERPs only during a
      later time-window in both output modalities: waveforms started to diverge around
      400 ms, which corresponded to the end of a period of topographic stability
      starting at around 260 ms in both conditions. These stable electrophysiological
      maps lasted longer in the late than in the early-acquired condition and shifted
      the onset of the following periods of stable electrophysiological activity. Taken
      together, the findings are at odds with the multiple loci hypothesis, but support
      the hypothesis that AoA affects a single encoding level, namely the word-form
      encoding process.

PMID- 24887391
TI  - Detection of 'best' positive end-expiratory pressure derived from electrical
      impedance tomography parameters during a decremental positive end-expiratory
      pressure trial.
AB  - INTRODUCTION: This study compares different parameters derived from electrical
      impedance tomography (EIT) data to define 'best' positive end-expiratory pressure
      (PEEP) during a decremental PEEP trial in mechanically-ventilated patients.
      'Best' PEEP is regarded as minimal lung collapse and overdistention in order to
      prevent ventilator-induced lung injury. METHODS: A decremental PEEP trial (from
      15 to 0 cm H2O PEEP in 4 steps) was performed in 12 post-cardiac surgery patients
      on the ICU. At each PEEP step, EIT measurements were performed and from this data
      the following were calculated: tidal impedance variation (TIV), regional
      compliance, ventilation surface area (VSA), center of ventilation (COV), regional
      ventilation delay (RVD index), global inhomogeneity (GI index), and intratidal
      gas distribution. From the latter parameter we developed the ITV index as a new
      homogeneity parameter. The EIT parameters were compared with dynamic compliance
      and the PaO2/FiO2 ratio. RESULTS: Dynamic compliance and the PaO2/FiO2 ratio had
      the highest value at 10 and 15 cm H2O PEEP, respectively. TIV, regional
      compliance and VSA had a maximum value at 5 cm H2O PEEP for the non-dependent
      lung region and a maximal value at 15 cm H2O PEEP for the dependent lung region.
      GI index showed the lowest value at 10 cm H2O PEEP, whereas for COV and the RVD
      index this was at 15 cm H2O PEEP. The intratidal gas distribution showed an equal
      contribution of both lung regions at a specific PEEP level in each patient.
      CONCLUSION: In post-cardiac surgery patients, the ITV index was comparable with
      dynamic compliance to indicate 'best' PEEP. The ITV index can visualize the PEEP
      level at which ventilation of the non-dependent region is diminished, indicating
      overdistention. Additional studies should test whether application of this
      specific PEEP level leads to better outcome and also confirm these results in
      patients with acute respiratory distress syndrome.

PMID- 24887392
TI  - 5alpha-Reductase inhibitors and risk of high-grade or lethal prostate cancer.
AB  - IMPORTANCE: 5alpha-Reductase inhibitors (5ARIs) are widely used for benign
      prostatic hyperplasia despite controversy regarding potential risk of high-grade
      prostate cancer with use. Furthermore, the effect of 5ARIs on progression and
      prostate cancer death remains unclear. OBJECTIVE: To determine the association
      between 5ARI use and development of high-grade or lethal prostate cancer. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective observational study of 38,058 men followed
      up for prostate cancer diagnosis and outcomes between 1996 and 2010 in the Health
      Professionals Follow-up Study. EXPOSURES: Use of 5ARIs between 1996 and 2010.
      MAIN OUTCOMES AND MEASURES: Cox proportional hazards models were used to estimate
      risk of prostate cancer diagnosis or development of lethal disease with 5ARI use,
      adjusting for possible confounders including prostate specific antigen testing.
      RESULTS: During 448,803 person-years of follow-up, we ascertained 3681 incident
      prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were
      high grade (Gleason sum [GS] 8-10), 1238 were GS 7, and 1600 were low grade (GS 2
      6). A total of 2878 (7.6%) men reported use of 5ARIs between 1996 and 2010. After
      adjusting for confounders, men who reported ever using 5ARIs over the study
      period had a reduced risk of overall prostate cancer (hazard ratio [HR], 0.77;
      95% CI, 0.65-0.91). 5ARI users had a reduced risk of GS 7 (HR, 0.67; 95% CI, 0.49
      0.91) and low-grade (GS 2-6) prostate cancer (HR, 0.74; 95% CI, 0.57-0.95). 5ARI
      use was not associated with risk of high-grade (GS 8-10) prostate cancer (HR,
      0.97; 95% CI, 0.64-1.46) or lethal disease (HR, 0.99; 95% CI, 0.58-1.69).
      Increased duration of use was associated with significantly lower risk of overall
      prostate cancer (HR for 1 year of additional use, 0.95; 95% CI, 0.92-0.99),
      localized (HR, 0.95; 95% CI, 0.90-1.00), and low-grade disease (HR, 0.92; 95% CI,
      0.85-0.99). There was no association for lethal, high-grade, or grade 7 disease.
      CONCLUSIONS AND RELEVANCE: While 5ARI use was not associated with developing high
      grade or lethal prostate cancer, it was associated with a reduction in low-grade,
      GS 7, and overall prostate cancer. Because the number of patients with high-grade
      or lethal prostate cancer in our cohort was limited, we cannot rule out potential
      risk of harm with 5ARI use.

PMID- 24887393
TI  - CD47-dependent immunomodulatory and angiogenic activities of extracellular
      vesicles produced by T cells.
AB  - Intercellular communication is critical for integrating complex signals in
      multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely
      interact during the recirculation and trans-endothelial migration of T cells. In
      addition to direct cell-cell contact, we show that T cell derived extracellular
      vesicles can interact with endothelial cells and modulate their cellular
      functions. Thrombospondin-1 and its receptor CD47 are expressed on
      exosomes/ectosomes derived from T cells, and these extracellular vesicles are
      internalized and modulate signaling in both T cells and endothelial cells.
      Extracellular vesicles released from cells expressing or lacking CD47
      differentially regulate activation of T cells induced by engaging the T cell
      receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial
      cell responses to vascular endothelial growth factor and tube formation in a CD47
      dependent manner. Uptake of T cell derived extracellular vesicles by recipient
      endothelial cells globally alters gene expression in a CD47-dependent manner.
      CD47 also regulates the mRNA content of extracellular vesicles in a manner
      consistent with some of the resulting alterations in target endothelial cell gene
      expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly
      regulates intercellular communication mediated by the transfer of extracellular
      vesicles between vascular cells. 

PMID- 24887394
TI  - In silico and Ex vivo approaches identify a role for toll-like receptor 4 in
      colorectal cancer.
AB  - BACKGROUND: Inflammation increases the risk of colorectal cancer (CRC). We and
      others have described a role for TLR4, the receptor for LPS, in colon cancer. To
      explore the relationships between TLR4 expression and CRC, we combined the
      strength of transcriptome array data and immunohistochemical (IHC) staining.
      METHODS: TLR4 signal intensity was scored in the stromal and epithelial
      compartments. Detection of differential expression between conditions of interest
      was performed using linear models, Cox proportional hazards models, and empirical
      Bayes methods. RESULTS: A strong association between TLR4 expression and survival
      was noted, though a dichotomous relationship between survival and specific TLR4
      transcripts was observed. Increasing TLR4 expression was seen with advancing
      tumor stage and was also over-expressed in some adenomas. IHC staining confirmed
      the positive relationship between TLR4 staining score in the CRC tumor stroma and
      epithelium with tumor stage, with up to 47% of colon cancer stroma positive for
      TLR4 staining. Increased TLR4 expression by IHC was also marginally associated
      with decreased survival. We now also describe that pericryptal myofibroblasts are
      responsible for a portion of the TLR4 stromal staining. CONCLUSIONS: Increased
      TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the
      important cancer-related outcomes of survival and stage.

PMID- 24887395
TI  - COX-2 protects against atherosclerosis independently of local vascular
      prostacyclin: identification of COX-2 associated pathways implicate Rgl1 and
      lymphocyte networks.
AB  - Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti
      inflammatory drugs (NSAIDs) are associated with increased cardiovascular side
      effects, including myocardial infarction. We and others have shown that COX-1 and
      not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re
      opening the question of how COX-2 might regulate cardiovascular health. In
      diseased, atherosclerotic vessels, the relative contribution of COX-2 to
      prostacyclin formation is not clear. Here we have used apoE(-/-)/COX-2(-/-) mice
      to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is
      independent of local prostacyclin release. These data further illustrate the need
      to look for new explanations, targets and pathways to define the
      COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from
      apoE(-/-)/COX-2(-/-) mice showed increased lymphocyte pathways that were
      validated by showing increased T-lymphocytes in plaques and elevated plasma Th1
      type cytokines. In addition, we identified a novel target gene, rgl1, whose
      expression was strongly reduced by COX-2 deletion across all examined tissues.
      This study is the first to demonstrate that COX-2 protects vessels against
      atherosclerotic lesions independently of local vascular prostacyclin and uses
      systems biology approaches to identify new mechanisms relevant to development of
      next generation NSAIDs.

PMID- 24887398
TI  - Multiple ant species tending lac insect Kerria yunnanensis (Hemiptera: Kerriidae)
      provide asymmetric protection against parasitoids.
AB  - This study investigated the effects of ant attendance on the parasitoid community
      and parasitism of lac insect Kerria yunnanensis aggregations in Yunnan province,
      China. We manipulated ant attendance to establish three treatments: (1) ant
      exclusion; (2) low ant attendance by several ant species; and (3) high ant
      attendance by Crematogaster macaoensis. Five parasitoid species were collected,
      with two species contributing 82.7 and 13.2% of total abundance respectively.
      Total parasitoid abundance was lowest in the February sample when K. yunnanensis
      was in its younger life stage, being significantly lower in the ant exclusion
      treatment. In April, all three treatments had significantly different parasitoid
      abundances, being highest in the ant exclusion treatment and the lowest in the
      high ant attendance treatment. When ants were present, there were strong negative
      relationships between total parasitoid abundance and ant abundance, with the
      relationships being dependent upon the ant species composition and abundance. The
      patterns of total parasitoid abundance were driven by the two most abundant
      parasitoid species. Parasitoid species richness did not differ among treatments
      or between sample times, however, multivariate analysis confirmed that overall
      parasitoid community structure differed significantly among treatments and
      between sample times, with the high ant attendance treatment differing most from
      the other two treatments. Interestingly the absence of ants did not result in
      increased parasitism from four of the five parasitoids. Ants in lac insect
      farming systems have a clear role for agricultural pest management. A full
      understanding of the asymmetric abilities of ants to influence parasitoid
      communities, and affect parasitism of hosts will require further experimental
      manipulation to assess the relative roles of 1) the abundance of each individual
      ant species on parasitoid access to hosts, 2) competition among parasitoids, and
      3) the interaction between the first two factors. 

PMID- 24887396
TI  - Chlorogenic acid decreases intestinal permeability and increases expression of
      intestinal tight junction proteins in weaned rats challenged with LPS.
AB  - Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides
      beneficial effects for human health. The objectives of this study were to
      investigate whether chlorogenic acid (CHA) could improve the intestinal barrier
      integrity for weaned rats with lipopolysaccharide (LPS) challenge. Thirty-two
      weaned male Sprague Dawley rats (21 +/- 1 d of age; 62.26 +/- 2.73 g) were
      selected and randomly allotted to four treatments, including weaned rat control,
      LPS-challenged and chlorogenic acid (CHA) supplemented group (orally 20 mg/kg and
      50 mg/kg body). Dietary supplementation with CHA decreased (P<0.05) the
      concentrations of urea and albumin in the serum, compared to the LPS-challenged
      group. The levels of IFN-gamma and TNF-alpha were lower (P<0.05) in the jejunal
      and colon of weaned rats receiving CHA supplementation, in comparison with the
      control group. CHA supplementation increased (P<0.05) villus height and the ratio
      of villus height to crypt depth in the jejunal and ileal mucosae under
      condictions of LPS challenge. CHA supplementation decreased (P<0.05) intestinal
      permeability, which was indicated by the ratio of lactulose to mannitol and serum
      DAO activity, when compared to weaned rats with LPS challenge.
      Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and
      occludin protein abundances in the jejunum and colon were increased (P<0.05) by
      CHA supplementation. Additionally, results of immunoblot analysis revealed that
      the amount of occludin in the colon was also increased (P<0.05) in CHA
      supplemented rats. In conclusion, CHA decreases intestinal permeability and
      increases intestinal expression of tight junction proteins in weaned rats
      challenged with LPS.

PMID- 24887399
TI  - Late dural relapse of a resected and irradiated pineal parenchymal tumor of
      intermediate differentiation.

PMID- 24887400
TI  - Primary osseous hemangiopericytoma in the thoracic spine.
AB  - Hemangiopericytoma (HPC) is a rare tumor of the central nervous system, most
      commonly found in the cranial cavity. HPCs in the spine are rare, and very few of
      them are primary osseous HPC. The aims of this study were to describe a rare case
      of primary osseous HPC in the thoracic spine and review the literature. A 54-year
      old man presented with a 3-month history of back pain. Aneuro logical examination
      revealed no motor or sensory deficits. Magnetic resonance imaging (MRI) and
      computed tomography (CT) scan showed a tumor originating from the bone structure
      of the T10 vertebra with paravertebral extension, and chest CT revealed pulmonary
      metastases. A laminectomy, face-totomy,and subtotal resection of the tumor was
      performed with posterior pedicle screw system fixation followed by radiotherapy.
      The post-operative course was uneventful. His back pain was resolved completely
      after surgery. The patient survived with tumor during the 18-month follow-up
      period. Histopathology and immunohistologic findings were consistent with HPC. On
      immunohistochemistry, the tumor was positive for vimentin and CD34, partially
      positive for S-100, but negative for EMA, desmin, CD117, and CD1a. A literature
      review identified eight such cases reported between 1942 and 2013. As a
      conclusion, clinical manifestations of primary osseous spinal HPCs are different
      from intraspinal meningeal HPCs. Although showing certain variability,
      histopathology and immunohistochemical examinations are essential to establish
      the diagnosis. Surgical resection and radiotherapy are the treatment of choice.
      *These authors contributed equally to this work.

PMID- 24887397
TI  - Changes in abundance of oral microbiota associated with oral cancer.
AB  - Individual bacteria and shifts in the composition of the microbiome have been
      associated with human diseases including cancer. To investigate changes in the
      microbiome associated with oral cancers, we profiled cancers and anatomically
      matched contralateral normal tissue from the same patient by sequencing 16S rDNA
      hypervariable region amplicons. In cancer samples from both a discovery and a
      subsequent confirmation cohort, abundance of Firmicutes (especially
      Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased
      relative to contralateral normal samples from the same patient. Significant
      decreases in abundance of these phyla were observed for pre-cancers, but not when
      comparing samples from contralateral sites (tongue and floor of mouth) from
      healthy individuals. Weighted UniFrac principal coordinates analysis based on 12
      taxa separated most cancers from other samples with greatest separation of node
      positive cases. These studies begin to develop a framework for exploiting the
      oral microbiome for monitoring oral cancer development, progression and
      recurrence. 

PMID- 24887401
TI  - Clinical and morphological variability of the E396K mutation in the neurofilament
      light chain gene in patients with Charcot-Marie- Tooth disease type 2E.
AB  - Mutations in the neurofilament light chain (NEFL) gene mostly cause autosomal
      dominant axonal Charcot-Marie- Tooth neuropathy (CMT2E). The mutation c.1186G>A,
      p.E396K has been reported in seven unrelated families so far, however, the
      phenotypic spectrum has not been fully elucidated. Here we describe nine patients
      with the E396K mutation who had a strikingly discordant clinical severity. The
      clinical picture in family I (patients I,1-II,8) was characterized by childhood
      onset, distal and proximal pareses, and loss of ambulation in the 6th decade of
      life, whereas onset was at age 50 years in patient 9, who had no affected
      relatives. Electrophysiology and sural nerve biopsy revealed a mixed axonal and
      demyelinating neuropathy, along with probably coincidental inflammatory small
      vessel disease in patient 9. Biopsy results in family I suggest that not only
      axons but also Schwann cells may be primary disease targets in CMT2E.
      Considerably elevated CK levels in all affected adults of family I as well as
      pronounced myopathic changes in skeletal muscle biopsies point towards an
      accompanying muscle involvement as a primary target. Our findings reveal an
      extended phenotype of CMT2E caused by an identical missense mutation of the NEFL
      gene. 

PMID- 24887402
TI  - Effects of healthy ageing on activation pattern within the primary motor cortex
      during movement and motor imagery: an fMRI study.
AB  - The increase in older adults over the coming decades will be accompanied by a
      greater burden of chronic neurological diseases affecting the motor system. The
      motor system adapts to maintain motor performance with the primary motor cortex
      (BA4) emerging as a pivotal node within this neuroplastic process. Studies of
      ageing often consider BA4 a homogenous area but cytoarchitectonic studies have
      revealed two subdivisions, an anterior (BA4a) and posterior subdivision (BA4p).
      Here we focus upon the effects of ageing on the involvement of BA4a and BA4p
      during movement and motor imagery (MI). Thirty-one right-handed healthy
      volunteers were recruited and screened for their ability to perform imagery (5
      subjects excluded). The sample was split into an older group (n = 13, mean age
      56.4 SD 9.4) and a younger group (n = 13, mean age 27.4 SD 5.3). We used an fMRI
      block-design (auditory-paced [1 Hz] right hand finger-thumb opposition sequence
      [2,3,4,5, 2...]) with MI & rest and actual movement & rest. We explored the
      distribution-based clustering and weighted laterality index within BA4a and BA4p.
      The involvement of BA4p during MI (measured with distribution-based clustering)
      was significantly greater in the older group (p<0.05) than in the younger group.
      Hemispheric balance of BA4p decreased with age during MI (Spearman rho -0.371;
      p<0.05), whereas that of BA4a decreased with age during actual movement (Spearman
      rho = -0.458 p<0.01). Irrespective of age, we found BA4 is involved during motor
      imagery, strengthening the rationale for its potential use in older subjects.
      These findings suggest that the functions of the subdivisions of BA4 are
      differentially affected by ageing and have implications regarding how ageing
      affects the cognitive processes underlying motor functions.

PMID- 24887403
TI  - Comparative proteomics analyses of Kobresia pygmaea adaptation to environment
      along an elevational gradient on the central Tibetan Plateau.
AB  - Variations in elevation limit the growth and distribution of alpine plants
      because multiple environmental stresses impact plant growth, including sharp
      temperature shifts, strong ultraviolet radiation exposure, low oxygen content,
      etc. Alpine plants have developed special strategies to help survive the harsh
      environments of high mountains, but the internal mechanisms remain undefined.
      Kobresia pygmaea, the dominant species of alpine meadows, is widely distributed
      in the Southeastern Tibet Plateau, Tibet Autonomous Region, China. In this study,
      we mainly used comparative proteomics analyses to investigate the dynamic protein
      patterns for K. pygmaea located at four different elevations (4600, 4800, 4950
      and 5100 m). A total of 58 differentially expressed proteins were successfully
      detected and functionally characterized. The proteins were divided into various
      functional categories, including material and energy metabolism, protein
      synthesis and degradation, redox process, defense response, photosynthesis, and
      protein kinase. Our study confirmed that increasing levels of antioxidant and
      heat shock proteins and the accumulation of primary metabolites, such as proline
      and abscisic acid, conferred K. pygmaea with tolerance to the alpine environment.
      In addition, the various methods K. pygmaea used to regulate material and energy
      metabolism played important roles in the development of tolerance to
      environmental stress. Our results also showed that the way in which K. pygmaea
      mediated stomatal characteristics and photosynthetic pigments constitutes an
      enhanced adaptation to alpine environmental stress. According to these findings,
      we concluded that K. pygmaea adapted to the high-elevation environment on the
      Tibetan Plateau by aggressively accumulating abiotic stress-related metabolites
      and proteins and by the various life events mediated by proteins. Based on the
      species'lexible physiological and biochemical processes, we surmised that
      environment change has only a slight impact on K. pygmaea except for possible
      impacts to populations on vulnerable edges of the species' range. 

PMID- 24887404
TI  - Ehlers-Danlos syndrome versus cleidocranial dysplasia.

PMID- 24887406
TI  - Uridine prevents tamoxifen-induced liver lipid droplet accumulation.
AB  - BACKGROUND: Tamoxifen, an agonist of estrogen receptor, is widely prescribed for
      the prevention and long-term treatment of breast cancer. A side effect of
      tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver
      disease. Prevention of tamoxifen-induced fatty liver has the potential to improve
      the safety of long-term tamoxifen usage. METHODS: Uridine, a pyrimidine
      nucleoside with reported protective effects against drug-induced fatty liver, was
      co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were
      evaluated with lipid visualization using coherent anti-Stokes Raman scatting
      (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and
      liquid chromatography coupled with mass spectrometry (LC-MS) measurement of
      membrane phospholipid. Blood TAG and cholesterol levels were measured.
      Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen
      and/or uridine was evaluated by measuring oxygen consumption rate with an
      extracellular flux analyzer. Liver protein lysine acetylation profiles were
      evaluated with 1D and 2D Western blots. In addition, the relationship between
      endogenous uridine levels, fatty liver, and tamoxifen administration was
      evaluated in transgenic mice UPase1-/-and UPase1-TG. RESULTS: Uridine co
      administration prevented tamoxifen-induced liver lipid droplet accumulation in
      mice. The most prominent effect of uridine co-administration with tamoxifen was
      the stimulation of liver membrane phospholipid biosynthesis. Uridine had no
      protective effect against tamoxifen-induced impairment to mitochondrial
      respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine
      had no effect on tamoxifen-induced changes to liver protein acetylation profile.
      Transgenic mice UPase1-/-with increased pyrimidine salvage activity were
      protected against tamoxifen-induced liver lipid droplet accumulation. In
      contrast, UPase1-TG mice with increased pyrimidine catabolism activity had
      intrinsic liver lipid droplet accumulation, which was aggravated following
      tamoxifen administration. CONCLUSION: Uridine co-administration was effective at
      preventing tamoxifen-induced liver lipid droplet accumulation. The ability of
      uridine to prevent tamoxifen-induced fatty liver appeared to depend on the
      pyrimidine salvage pathway, which promotes biosynthesis of membrane phospholipid.

PMID- 24887407
TI  - Association between the melanopsin gene polymorphism OPN4*Ile394Thr and
      sleep/wake timing in Japanese university students.
AB  - BACKGROUND: In our previous studies, we found that the Ile394Thr SNP in the
      melanopsin gene (OPN4) was functionally associated with the pupillary light
      reflex. This indicates the possibility that OPN4*Ile394Thr is associated with
      other non-image forming responses. The aim of this study was therefore to
      determine whether OPN4*Ile394Thr is associated with sleep/wake timing. METHODS: A
      total of 348 healthy Japanese university students participated in this study.
      Scalp hair was used to genotype the Ile394Thr SNP of OPN4. Sleep habits,
      including bedtime, wake time and sleep duration, were assessed separately for
      weekdays and weekends. A total of 328 samples, including 223 samples with TT
      genotype, 91 with TC genotype and 14 with CC genotype, were used for statistical
      analysis. No significant difference in age or male/female distribution was found
      among the three genotype groups. RESULTS: There was no significant difference in
      circadian preference among the genotype groups. During weekdays, bedtime, wake
      time and midpoint of sleep for CC subjects were significantly later than those
      for TT and TC subjects. However, there was no difference between TT and TC
      subjects in any of their sleep habits. During weekends, bedtime of CC subjects
      was significantly later than those of TT and TC subjects, and the midpoint of
      sleep of CC subjects was significantly later than that of TC subjects.
      CONCLUSIONS: Our findings demonstrated that OPN4*Ile394Thr is associated with
      sleep/wake timing. We also found that the sleep/wake timing of subjects with the
      CC genotype was later than that of subjects with the TT or TC genotype.

PMID- 24887408
TI  - The clinical application value of cytokines in treating infectious diseases.
AB  - We performed a prospective study to evaluate the abilities of inflammatory
      cytokines to rule out the potential risk of sepsis and intracranial infection and
      to estimate the function of inflammatory cytokines in discriminating Gram
      negative bacteria from Gram-positive ones through ROC analysis. During the course
      of the study, Levels of serum inflammatory cytokines were measured by flow
      cytometry at the onset of diseases of patients who suffered from sepsis or
      intracranial infection. A total of 299 cases of sepsis and 43 cases of
      intracranial infection were observed during the study. It is noticed that there
      is no difference of inflammatory cytokine levels between sepsis group and
      intracranial infection group. The area under ROC curve (AUC) of cytokines, such
      as IL-2, IL-6 and IL-10 were 0.901, 0.86, 0.888, respectively, which was employed
      to rule out the diseases of sepsis and intracranial infection. Through
      comparisons with the patients who were infected by Gram-positive bacteria or Gram
      negative ones, it is estimated that IL-6 and IL-10 sharply elevated in patients
      with Gram-negative bacteria infection (median levels, pg/mL: IL-6: 116.6 vs.
      25.4, P = 0.000; IL-10: 13.7 vs. 6.3, P = 0.000). Additionally, IL-2
      significantly decreased when patients suffered from Gram-negative bacteria
      infection (median levels, pg/mL: IL-2: 2.2 vs. 2.7, P = 0.031). The AUCs for
      detecting cytokines, including IL-2, IL-10 and LOGREGR.Pred_IL-2+IL-10 were 0.581
      (95% CI, 0.526 to 0.634), 0.661 (95% CI, 0.608 to 0.712) and 0.735 (95% CI, 0.685
      to 0.782), respectively, which was used to evaluate the function of inflammatory
      cytokines in discriminating Gram-negative bacteria from Gram-positive ones
      infection. This paper indicates that IL-2, IL-6 and IL-10 are effective
      biomarkers to rule out sepsis and intracranial infection. Additionally, the
      combination of IL-2 and IL-10 is an effective biomarkers to diagnose whether
      patients afflicted by Gram-negative bacteria. 

PMID- 24887405
TI  - Sex differences in anxiety and depression clinical perspectives.
AB  - Sex differences are prominent in mood and anxiety disorders and may provide a
      window into mechanisms of onset and maintenance of affective disturbances in both
      men and women. With the plethora of sex differences in brain structure, function,
      and stress responsivity, as well as differences in exposure to reproductive
      hormones, social expectations and experiences, the challenge is to understand
      which sex differences are relevant to affective illness. This review will focus
      on clinical aspects of sex differences in affective disorders including the
      emergence of sex differences across developmental stages and the impact of
      reproductive events. Biological, cultural, and experiential factors that may
      underlie sex differences in the phenomenology of mood and anxiety disorders are
      discussed. 

PMID- 24887409
TI  - Exploring the functional residues in a flavin-binding fluorescent protein using
      deep mutational scanning.
AB  - Flavin mononucleotide (FMN)-based fluorescent proteins are versatile reporters
      that can monitor various cellular processes in both aerobic and anaerobic
      conditions. However, the understanding of the role of individual amino acid
      residues on the protein function has been limited and has restricted the
      development of better functional variants. Here we examine the functional amino
      acid residues of Escherichia coli flavin mononucleotide binding fluorescent
      protein (EcFbFP) using the application of high-throughput sequencing of
      functional variants, termed deep mutational scanning. The variants were
      classified into 329 function-retained (FR) and 259 function-loss (FL) mutations,
      and further the mutational enrichment in each amino acid residues was weighed to
      find the functionally important residues of EcFbFP. We show that the crucial
      amino acid residues of EcFbFP lie among the FMN-binding pocket, turns and loops
      of the protein where conformation changes occur, and spatially clustered residues
      near the E56-K97 salt bridges. In addition, the mutational sensitivity of the
      critical residues was confirmed by site-directed mutagenesis. The deep mutational
      scanning of EcFbFP has demonstrated important implications for constructing
      better functioning protein variants. 

PMID- 24887411
TI  - Identification of glyceraldehyde 3-phosphate dehydrogenase sequence and
      expression profiles in tree shrew (Tupaia belangeri).
AB  - The tree shrews (Tupaia belangeri) diverged from the primate order (Primates) and
      are classified as Scandentia, a separate taxonomic group of mammals. The tree
      shrew has been suggested to use an animal model to study human disease but the
      genomic sequences of tree shrew is largely unidentified. Here we identified the
      full-length cDNA sequence of a housekeeping gene, Glyceraldehyde 3-phosphate
      Dehydrogenase (GAPDH), in tree shrew. We further constructed a phylogenetic
      family tree base on GAPDH molecules of various organisms and compared GAPDH
      sequences with human and other small experimental animals. These study revealed
      that tree shrew was closer to human than mouse, rat, rabbit and guinea pig. The
      Quantitative Reverse Transcription PCR and western blot analysis further
      demonstrated that GAPDH expressed in various tissues in tree shrew as a general
      conservative housekeeping proteins as in human. Our findings provide the novel
      genetic knowledge of the tree shrew and strong evidences that tree shrew can be
      an experimental model system to study human disorders. 

PMID- 24887410
TI  - Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas
      aeruginosa infection by its influence on neutrophil function in vivo.
AB  - Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also
      known as antimicrobial peptides) and an important component of innate host
      defence against infection. In addition to microbicidal potential, these peptides
      have properties with the capacity to modulate inflammation and immunity. However,
      the extent to which such properties play a significant role during infection in
      vivo has remained unclear. A murine model of acute P. aeruginosa lung infection
      was utilised, demonstrating cathelicidin-mediated enhancement of bacterial
      clearance in vivo. The delivery of exogenous synthetic human cathelicidin LL-37
      was found to enhance a protective pro-inflammatory response to infection,
      effectively promoting bacterial clearance from the lung in the absence of direct
      microbicidal activity, with an enhanced early neutrophil response that required
      both infection and peptide exposure and was independent of native cathelicidin
      production. Furthermore, although cathelicidin-deficient mice had an intact early
      cellular inflammatory response, later phase neutrophil response to infection was
      absent in these animals, with significantly impaired clearance of P. aeruginosa.
      These findings demonstrate the importance of the modulatory properties of
      cathelicidins in pulmonary infection in vivo and highlight a key role for
      cathelicidins in the induction of protective pulmonary neutrophil responses,
      specific to the infectious milieu. In additional to their physiological roles,
      CHDP have been proposed as future antimicrobial therapeutics. Elucidating and
      utilising the modulatory properties of cathelicidins has the potential to inform
      the development of synthetic peptide analogues and novel therapeutic approaches
      based on enhancing innate host defence against infection with or without direct
      microbicidal targeting of pathogens. 

PMID- 24887412
TI  - Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in
      rats with fulminant hepatic failure.
AB  - The mechanism of renal failure during fulminant hepatic failure (FHF) or end
      stage of liver disease is not fully understood. The present study aims to
      delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute
      hepatic failure. A rat model of renal insufficiency in severe liver injury was
      established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR
      was evaluated by continuous infusion of fluorescein isothiocyanate-inulin with
      implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe
      hepatocyte toxicity as evidenced by liver histology and biochemical tests,
      whereas renal morphology remained normal. GFR was reduced by 33% of the controls
      12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a
      marked increase in serum TNF-alpha and ET-1 levels as well as significantly
      upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1)
      expression. The upregulated IP3R1 expression was abrogated by the treatment of
      anti-TNF-alpha antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which
      blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either
      TNF-alpha antibodies or 2-APB also significantly improved the compromised GFR,
      elevated serum urea nitrogen and creatinine levels, and reversed the decrease in
      glomerular inulin space and the increase in glomerular calcium content in
      GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT
      levels was much more attenuated by anti-TNF-alpha antibodies than by 2-APB. Liver
      histology further confirmed that anti-TNF-alpha antibodies conferred better
      protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-alpha over
      production is responsible for decreased GFR through IP3R1 overexpression, and the
      compromised GFR resulted in the development of acute renal failure in rats with
      FHF.

PMID- 24887413
TI  - Sustainable control of onchocerciasis: ocular pathology in onchocerciasis
      patients treated annually with ivermectin for 23 years: a cohort study.
AB  - The evolution and persistence of ocular pathology was assessed in a cohort of
      Onchocerca volvulus infected patients treated annually with ivermectin for 23
      years. Patients were resident in rural Central and Kara Region of Togo and ocular
      examinations included testing of visual acuity, slit lamp examination of the
      anterior eye segment and the eye fundus by ophthalmoscopy. Before ivermectin
      treatment, vivid O.volvulus microfilariae (MF) were observed in the right and
      left anterior eye chamber in 52% and 42% of patients (n = 82), and dead MF were
      seen in the right and left cornea in 24% and 15% of cases, respectively. At 23
      years post initial treatment (PIT), none of the patients (n = 82) presented with
      MF in the anterior chamber and cornea. A complete resolution of punctate
      keratitis (PK) lesions without observable corneal scars was present at 23 years
      PIT (p<0.0001), and sclerosing keratitits (SK) lessened by half, but mainly in
      patients with lesions at early stage of evolution. Early-stage iridocyclitis
      diminished from 42%(rE) and 40%(lE) to 13% (rE+lE)(p<0.0001), but advanced
      iridocyclitis augmented (p<0.001) at 23 years PIT compared to before ivermectin.
      Advanced-stage papillitis and chorioretinitis did not regress, while early-stage
      papillitis present in 28%(rE) and 27%(lE) of patients at before ivermectin
      regressed to 17%(rE) and 18%(lE), and early-stage chorioretinitis present in
      51%(rE+lE) of cases at before ivermectin was observed in 12%(rE) and 13%(lE) at
      23 years PIT (p<0.0001). Thus, regular annual ivermectin treatment eliminated and
      prevented the migration of O. volvulus microfilariae into the anterior eye
      chamber and cornea; keratitis punctata lesions resolved completely and early
      stage sclerosing keratitits and iridocyclitis regressed, whilst advanced lesions
      of the anterior and posterior eye segment remained progressive. In conclusion,
      annual ivermectin treatments may prevent the emergence of ocular pathology in
      those populations still exposed to O.volvulus infection. TRIAL REGISTRATION:
      www.pactr.org PACTR201303000464219).

PMID- 24887416
TI  - Biosensing platform based on graphene oxide via self-assembly induced by synergic
      interactions.
AB  - A novel self-assembled glucose biosensor based on graphene oxide (GO) was
      constructed by using 1-pyrenebutyric acid-N-hydroxysuccinimide ester (PANHS) as
      linking molecular. The stepwise self-assembly process was performed for PANHS
      anchoring in N,N-dimethylformamide (DMF) solvent and the further glucose oxidase
      (GOD) binding in aqueous solution, respectively. The molecular interactions and
      the morphologic properties were characterized by Fourier transform infrared
      spectroscopy (FTIR), field emission scanning electronic microscopy (FESEM), and
      atomic force microscopy (AFM). In addition, the quantitative loadings of anchored
      PANHS and GOD were well elucidated by surface plasmon resonance (SPR)
      measurements. The obtained novel glucose sensor exhibited satisfactory analytical
      performance to glucose: wide linear range (4.0*10(-6) to 4.4*10(-3) M), fast
      response (10s), high sensitivity (40.5+/-0.4 mA M(-1) cm(-2)), and low detection
      limit (2 MUM, S/N=3). Furthermore, the biosensor exhibited excellent long-term
      stability and satisfactory reproducibility.

PMID- 24887415
TI  - A novel Botrytis species is associated with a newly emergent foliar disease in
      cultivated Hemerocallis.
AB  - Foliar tissue samples of cultivated daylilies (Hemerocallis hybrids) showing the
      symptoms of a newly emergent foliar disease known as 'spring sickness' were
      investigated for associated fungi. The cause(s) of this disease remain obscure.
      We isolated repeatedly a fungal species which proved to be member of the genus
      Botrytis, based on immunological tests. DNA sequence analysis of these isolates,
      using several different phyogenetically informative genes, indicated that they
      represent a new Botrytis species, most closely related to B. elliptica (lily
      blight, fire blight) which is a major pathogen of cultivated Lilium. The
      distinction of the isolates was confirmed by morphological analysis of asexual
      sporulating cultures. Pathogenicity tests on Hemerocallis tissues in vitro
      demonstrated that this new species was able to induce lesions and rapid tissue
      necrosis. Based on this data, we infer that this new species, described here as
      B. deweyae, is likely to be an important contributor to the development of
      'spring sickness' symptoms. Pathogenesis may be promoted by developmental and
      environmental factors that favour assault by this necrotrophic pathogen. The
      emergence of this disease is suggested to have been triggered by breeding-related
      changes in cultivated hybrids, particularly the erosion of genetic diversity. Our
      investigation confirms that emergent plant diseases are important and deserve
      close monitoring, especially in intensively in-bred plants. 

PMID- 24887414
TI  - Immunohistochemical and molecular characteristics with prognostic significance in
      diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with
      marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the
      prognostic value of immunohistochemical markers derived from the gene expression
      profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1
      protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC
      and FOXP1 using fluorescence in situ hybridization and assessed their prognostic
      significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene
      alteration (rearrangement and/or amplification) was associated with the non
      germinal center B subtype (non-GCB). BCL2 translocation was associated with the
      GCB phenotype, and BCL2 protein expression was associated with the translocation
      and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases,
      and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly
      of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the
      MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of
      cases. We detected an association between high FOXP1 expression and a high
      proliferation rate as well as a significant positive correlation between MYC
      overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were
      significant predictors of overall survival. The co-expression of MYC and BCL2
      confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas
      cases negative for both markers had the best outcomes. Our study confirms that
      DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor
      prognosis and establishes a significant positive correlation with MYC and FOXP1
      over-expression in this entity. 

PMID- 24887417
TI  - Intergenerational genomic DNA methylation patterns in mouse hybrid strains.
AB  - BACKGROUND: DNA methylation is a contributing factor to both rare and common
      human diseases, and plays a major role in development and gene silencing. While
      the variation of DNA methylation among individuals has been partially
      characterized, the degree to which methylation patterns are preserved across
      generations is still poorly understood. To determine the extent of methylation
      differences between two generations of mice we examined DNA methylation patterns
      in the livers of eight parental and F1 mice from C57BL/6J and DBA/2J mouse
      strains using bisulfite sequencing. RESULTS: We find a large proportion of
      reproducible methylation differences between C57BL/6J and DBA/2J chromosomes in
      CpGs, which are highly heritable between parent and F1 mice. We also find sex
      differences in methylation levels in 396 genes, and 11% of these are
      differentially expressed between females and males. Using a recently developed
      approach to identify allelically methylated regions independently of genotypic
      differences, we identify 112 novel putative imprinted genes and microRNAs, and
      validate imprinting at the RNA level in 10 of these genes. CONCLUSIONS: The
      majority of DNA methylation differences among individuals are associated with
      genetic differences, and a much smaller proportion of these epigenetic
      differences are due to sex, imprinting or stochastic intergenerational effects.
      Epigenetic differences can be a determining factor in heritable traits and should
      be considered in association studies for molecular and clinical traits, as we
      observed that methylation differences in the mouse model are highly heritable and
      can have functional consequences on molecular traits such as gene expression.

PMID- 24887419
TI  - The mechanistic target for rapamycin pathway is related to the phosphorylation
      score for estrogen receptor-alpha in human breast tumors in vivo.
AB  - INTRODUCTION: A phosphorylation score for estrogen receptor-alpha (ERalpha),
      called P7 score, was shown previously to be an independent prognostic factor in
      breast cancer patients treated with tamoxifen. Since mechanistic target of
      rapamycin (mTOR) activation is implicated in resistance to endocrine therapy in
      breast cancer we determined whether mechanistic target of rapamycin complex 1
      (mTORC1) activation, measured by phosphorylation on S2448 (p-mTOR), was
      associated with the P7-score and/or clinical outcome in the same cohort. METHODS:
      mTOR phosphorylation status was determined at S2448 residue in vivo by
      immunohistochemistry in a cohort of more than 400 well-characterized ERalpha
      positive breast tumors. MCF7 cells were treated with estrogen and activation of
      mTOR pathway was determined by Western blotting. RESULTS: Contrary to earlier
      reports, p-mTOR expression, measured by immunohistochemistry, was negatively
      associated with size and nodal status. Additionally, p-S2448 mTOR expression was
      positively correlated with p-S118- ERalpha, p-S167-ERalpha and p-S282-ERalpha but
      negatively correlated with p-T311- ERalpha. Consistent with these, p-S2448 mTOR
      was negatively associated with P7-score and was significantly associated with
      overall survival (OS) (hazard ratio (HR) = 0.61, P = 0.028, 95% confidence
      interval (CI) 0.39 to 0.95, n = 337) and relapse-free survival (HR = 0.58, P =
      0.0032, 95% CI 0.41 to 0.83, n = 337) following univariate but not multivariate
      analysis. Furthermore, we show that estrogen can regulate phosphorylation of mTOR
      and its down stream target p70S6 kinase. Additionally, recombinant mTOR can
      phosphorylate ERalpha in vitro. CONCLUSIONS: These data suggest that in breast
      tumors where there is intact estrogen regulated signaling, mTOR is regulated by
      estrogen and therefore associated with an increased likelihood of responsiveness
      to endocrine therapy.

PMID- 24887418
TI  - Effectiveness of brief interventions as part of the Screening, Brief Intervention
      and Referral to Treatment (SBIRT) model for reducing the nonmedical use of
      psychoactive substances: a systematic review.
AB  - BACKGROUND: The purpose of this systematic review is to assess the effectiveness
      of brief interventions (BIs) as part of the Screening, Brief Intervention, and
      Referral to Treatment (SBIRT) model for reducing the nonmedical use of
      psychoactive substances. METHODS: Bibliographic databases (including MEDLINE,
      Embase, The Cochrane Library, CINAHL, and PsycINFO to April 2012) and gray
      literature sources were searched. We included randomized controlled trials that
      opportunistically screened adolescents or adults and then provided a one-to-one,
      verbal BI to those at risk of substance-use harm. Of interest was the nonmedical
      use of psychoactive substances (for example, drugs prohibited by international
      law), excluding alcohol, nicotine, and caffeine. Interventions comprised four or
      fewer sessions and were compared with no/delayed intervention or provision of
      information only. Studies were assessed for bias using the Cochrane risk of bias
      tool. Results were synthesized narratively. Evidence was interpreted according to
      the GRADE framework. RESULTS: We identified 8,836 records. Of these, five studies
      met our inclusion criteria. Two studies compared BI with no BI, and three studies
      compared BI with information only. Studies varied in characteristics such as
      substances targeted, screening procedures, and BI administered. Outcomes were
      mostly reported by a single study, leading to limited or uncertain confidence in
      effect estimates. CONCLUSIONS: Insufficient evidence exists as to whether BIs, as
      part of SBIRT, are effective or ineffective for reducing the use of, or harms
      associated with nonmedical use of, psychoactive substances when these
      interventions are administered to nontreatment-seeking, screen-detected
      populations. Updating this review with emerging evidence will be important. TRIAL
      REGISTRATION: CRD42012002414.

PMID- 24887420
TI  - Preclinical therapeutic potential of a nitrosylating agent in the treatment of
      ovarian cancer.
AB  - This study examines the role of s-nitrosylation in the growth of ovarian cancer
      using cell culture based and in vivo approaches. Using the nitrosylating agent, S
      nitrosoglutathione (GSNO), a physiological nitric oxide molecule, we show that
      GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant
      ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5,
      OVCAR7, OVCAR8, OVCAR10, PE01 and PE04) in a dose dependent manner. GSNO
      treatment abrogated growth factor (HB-EGF) induced signal transduction including
      phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles
      in ovarian cancer growth and progression. To examine the therapeutic potential of
      GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780
      ovarian carcinoma cell line (2 * 10(6)) were orally administered GSNO at the dose
      of 1 mg/kg body weight. Daily oral administration of GSNO significantly
      attenuated tumor mass (p<0.001) in the peritoneal cavity compared to vehicle
      (phosphate buffered saline) treated group at 4 weeks. GSNO also potentiated
      cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model.
      GSNO's nitrosylating ability was reflected in the induced nitrosylation of
      various known proteins including NFkappaB p65, Akt and EGFR. As a novel finding,
      we observed that GSNO also induced nitrosylation with inverse relationship at
      tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance
      and cell proliferation in ovarian cancer and in cancer in general. Overall, our
      study underlines the significance of S-nitrosylation of key cancer promoting
      proteins in modulating ovarian cancer and proposes the therapeutic potential of
      nitrosylating agents (like GSNO) for the treatment of ovarian cancer alone or in
      combination with chemotherapeutic drugs.

PMID- 24887421
TI  - Loss of Sonic hedgehog leads to alterations in intestinal secretory cell
      maturation and autophagy.
AB  - BACKGROUND: Intestinal epithelial cells express the Sonic and Indian hedgehog
      ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no
      studies have specifically addressed the singular role of intestinal epithelial
      cell Sonic hedgehog signaling. The aim of this study was to investigate the
      specific role of Sonic hedgehog in adult ileal epithelial homeostasis.
      METHODOLOGY/PRINCIPAL FINDINGS: A Sonic hedgehog intestinal epithelial
      conditional knockout mouse model was generated. Assessment of ileal histological
      abnormalities, crypt epithelial cell proliferation, epithelial cell fate,
      junctional proteins, signaling pathways, as well as ultrastructural analysis of
      intracellular organelles were performed in control and mutant mice. Mice lacking
      intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus
      length, decreased crypt proliferation as well as a decrease in the number of
      ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth
      cells during adult life. These secretory cells also exhibited disruption of their
      secretory products in mutant mice. Ultrastructural microscopy analysis revealed a
      dilated ER lumen in secretory cells. This phenotype was also associated with a
      decrease in autophagy. CONCLUSIONS/SIGNIFICANCE: Altogether, these findings
      indicate that the loss of Sonic hedgehog can lead to ileal secretory cell
      modifications indicative of endoplasmic reticulum stress, accompanied by a
      significant reduction in autophagy.

PMID- 24887423
TI  - QT is longer in drug-free patients with schizophrenia compared with age-matched
      healthy subjects.
AB  - The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations
      induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene
      for schizophrenia. Additionally, the disturbance of autonomic control, which
      affects the QT interval, is known in schizophrenia. Therefore, we speculate that
      schizophrenic patients have characteristic features in terms of the QT interval
      in addition to the effect of antipsychotic medication. The QT interval of
      patients with schizophrenia not receiving antipsychotics (n = 85) was compared
      with that of patients with schizophrenia receiving relatively large doses of
      antipsychotics (n = 85) and healthy volunteers (n = 85). The QT interval was
      corrected using four methods (Bazett, Fridericia, Framingham or Hodges method).
      In ANCOVA with age and heart rate as covariates, patients not receiving
      antipsychotic treatment had longer QT intervals than did the healthy volunteers,
      but antipsychotics prolonged the QT interval regardless of the correction method
      used (P<0.01). Schizophrenic patients with and without medication had a
      significantly higher mean heart rate than did the healthy volunteers, with no
      obvious sex-related differences in the QT interval. The QT interval prolongation
      may be manifestation of a certain biological feature of schizophrenia. 

PMID- 24887425
TI  - Directional and enhanced spontaneous emission with a corrugated metal probe.
AB  - A three-dimensional corrugated metal tapered probe with surface corrugated
      gratings at the tip apex is proposed and investigated theoretically, which leads
      to an obvious emission beaming effect of spontaneous emission from a single
      emitter near the probe. In contrast with conventional apertureless metal probes,
      where only the enhancement of an optical near-field is concerned, the corrugated
      probe is able to manipulate local excitation intensity and far-field emission
      direction simultaneously. The angular emission from a single dipole source, being
      placed close to the corrugated probe, falls into a cone with a maximum
      directivity angle of +/-11.6 degrees , which improves the collection efficiency
      25-fold. Such a probe simultaneously increases the localized field intensity to
      about twice as strong as the conventional bare tip. In addition, the radiation
      pattern is sensitive to the working wavelength and the dipole to tip-apex
      separation. These findings make a promising route to the development of plasmonic
      spontaneous emission manipulation based on corrugated tapered antenna-for
      instance, tip-enhanced spectroscopy, single-molecule sensing, and single-photon
      source.

PMID- 24887424
TI  - Rejection quantity in kidney transplant recipients is associated with increasing
      intracellular interleukin-2 in CD8+ T-cells.
AB  - BACKGROUND: CD8+ T-cells and interleukin-2 play an important role during organ
      rejection in kidney transplant recipients. Numerous studies showed increased
      interleukin-2 levels during acute rejection. The aim of our study is to show an
      association between intracellular interleukin-2 in CD8+ T-cells and the incidence
      of those who underwent organ rejection in kidney transplant recipients. METHODS:
      407 transplant recipients were included into this study. The rejection incidence
      was investigated from the patient records. White blood cells from recipients were
      separated using a ficoll gradient. The cells were double-gated (CD3+ and CD8+)
      for the analysis of cellular percentage for intracellular interleukin-2 with a
      flow cytometer. RESULTS: The percentage of CD8+ cells with detectable
      intracellular interleukin-2 was significantly higher in renal transplant
      recipients with a documented rejection compared to recipients without any history
      of rejection (9.06+/-0.50, N=133 vs. 4.28+/-0.24, N=274, p<0.0001, t-test).
      Further, there was a significant increase in patients with one (8.02+/-0.54,
      N=80, p<0.0001, t-test), two (10.40+/-1.17, N=33, p<0.0001, t-test) or three
      (11.82+/-1.58, N=18, p<0.0001, t-test) rejection events. CONCLUSIONS: Past
      studies showed, that during acute organ rejection intracellular interleukin-2 is
      increased in cytotoxic T-cells, supposed to be a marker for this event. We were
      able to show, that intracellular interleukin-2 in CD8+ T-cells is also increased
      after organ rejection. Furthermore it seems to depend on the quantity of
      rejection events. Further studies in recipients with increased intracellular
      interleukin-2 in cytotoxic CD8+ T-cells and documented history of organ rejection
      are needed to identify this as a possible risk factor for further rejection
      events.

PMID- 24887426
TI  - Induction of neutralizing antibody response against four dengue viruses in mice
      by intramuscular electroporation of tetravalent DNA vaccines.
AB  - DNA vaccine against dengue is an interesting strategy for a prime/boost approach.
      This study evaluated neutralizing antibody (NAb) induction of a dengue
      tetravalent DNA (TDNA) vaccine candidate administered by intramuscular
      electroporation (IM-EP) and the benefit of homologous TDNA boosting in mice.
      Consensus humanized pre-membrane (prM) and envelope (E) of each serotypes, based
      on isolates from year 1962-2003, were separately cloned into a pCMVkan expression
      vector. ICR mice, five-six per group were immunized for three times (2-week
      interval) with TDNA at 100 ug (group I; 25 ug/monovalent) or 10 ug (group II; 2.5
      ug/monovalent). In group I, mice received an additional TDNA boosting 13 weeks
      later. Plaque reduction neutralization tests (PRNT) were performed at 4 weeks
      post-last immunization. Both 100 ug and 10 ug doses of TDNA induced high NAb
      levels against all DENV serotypes. The median PRNT50 titers were comparable among
      four serotypes of DENV after TDNA immunization. Median PRNT50 titers ranged 240
      320 in 100 ug and 160-240 in 10 ug groups (p = ns). A time course study of the
      100 ug dose of TDNA showed detectable NAb at 2 weeks after the second injection.
      The NAb peaked at 4 weeks after the third injection then declined over time but
      remained detectable up to 13 weeks. An additional homologous TDNA boosting
      significantly enhanced the level of NAb from the nadir for at least ten-fold
      (p<0.05). Of interest, we have found that the use of more recent dengue viral
      strain for both vaccine immunogen design and neutralization assays is critical to
      avoid a mismatching outcome. In summary, this TDNA vaccine candidate induced good
      neutralizing antibody responses in mice; and the DNA/DNA prime/boost strategy is
      promising and warranted further evaluation in non-human primates.

PMID- 24887427
TI  - Very late relapse of germ cell tumor as a teratoma: a case report and review of
      the literature.
AB  - Very late relapses of germ cell tumors (GCTs) are rare. There are few reports of
      relapses occurring beyond 20 years of initial treatment. Here we describe a case
      of a very late relapse of Stage I testicular non-seminomatous germ cell tumor 27
      years after orchiectomy. The relapse presented as a retroperitoneal mass in the
      precaval lymph nodes with negative tumor markers. It was resected and pathology
      confirmed it as metastatic teratoma. This case emphasizes the importance of
      lifelong surveillance for patients with GCTs. 

PMID- 24887428
TI  - Blunt chest trauma.
AB  - Blunt aortic injury is the most lethal injury of the thorax, of which aortic
      transection is the second leading cause of death. Pseudoaneurysm formation is
      seen in patients who survive the injury and arrive to the emergency department
      with small or partial-thickness tears of the aorta. In general, the proximal
      descending aorta is most commonly afflicted due to the relatively mobile aortic
      arch moving against the fixed descending aorta. There are several factors
      associated with a high risk of aortic injury including high-speed motor vehicle
      collision (MVC) accidents, unrestrained drivers and passengers, extensive
      impact/collision and abrupt deceleration of motor vehicles. In this case study, a
      28-year-old male patient with a thoracic aorta injury is presented. Diagnostic
      findings consistent with transection and/or dissection and a review of his
      surgical management are also discussed. 

PMID- 24887429
TI  - Scrotal enterocutaneous fistula: a rare initial presentation of inguinal hernia.
AB  - We describe the case of a 70-year-old man with a long history of inguinal hernia
      who finally presented to the emergency department with a scrotal enterocutaneous
      fistula. This is a rare complication of an incarcerated/obstructed direct
      inguinal hernia. We performed exploratory laparotomy with resection of the
      perforated small bowel and end-to-end anastamosis of the ileal segment using the
      purse-string suture at the deep inguinal ring. 

PMID- 24887431
TI  - Self-relevance does not moderate choice blindness in adolescents and children.
AB  - In two experiments we tested the choice blindness phenomenon in adolescents aged
      11-16 years (Experiment 1, N = 87) and children aged 7-10 years (Experiment 2, N
      = 117) for the first time. Analogous to previously reported findings with adult
      participants, we expected to replicate the robust effect in these age groups.
      Furthermore, we investigated the hypothesis that self-relevance of choices,
      defined as the extent to which the self is implicated in a choice, moderates the
      choice blindness effect in adolescents and children. To this end, we directly
      compared high and low self-relevance conditions. As expected, the choice
      blindness effect was robust across age groups. Little support was found for the
      idea that self-relevance moderates the choice blindness effect. Specifically, no
      effect of self-relevance on choice blindness was found in adolescents, while the
      findings in the child sample were inconsistent. Different possible
      interpretations of the results as well as the possible role of ambiguity for the
      choice blindness effect are discussed. 

PMID- 24887432
TI  - Cryo-EM structure of isomeric molluscan hemocyanin triggered by viral infection.
AB  - Hemocyanins (Hcs) of arthropods and mollusks function not only as oxygen
      transporters, but also as phenoloxidases (POs). In invertebrates, PO is an
      important component in the innate immune cascade, where it functions as the
      initiator of melanin synthesis, a pigment involved in encapsulating and killing
      of pathogenic microbes. Although structures of Hc from several species of
      invertebrates have been reported, the structural basis for how PO activity is
      triggered by structural changes of Hc in vivo remains poorly understood. Here, we
      report a 6.8 A cryo-electron microscopy (cryo-EM) structure of the isomeric form
      of hemocyanin, which was isolated from Abalone Shriveling syndrome-associated
      Virus (AbSV) infected abalone (Halitotis diversicolor), and build a pseudoatomic
      model of isomeric H. diversicolor hemocyanin 1 (HdH1). Our results show that,
      compared with native form of HdH1, the architecture of isomeric HdH1 turns into a
      more relaxed form. The interactions between certain functional units (FUs)
      present in the native form of Hc either decreased or were totally abolished in
      the isomeric form of Hc. As a result of that, native state Hc switches to its
      isomeric form, enabling it to play its role in innate immune responses against
      invading pathogens. 

PMID- 24887433
TI  - A profile of New Zealand 'Asian' participants of the 2008/09 Adult National
      Nutrition Survey: focus on dietary habits, nutrient intakes and health outcomes.
AB  - OBJECTIVE: To investigate similarities and differences in dietary habits,
      nutrient intakes and health outcomes of South Asians (SA) and East and South-East
      Asians (ESEA) and the New Zealand European and Other (NZEO) group, and to examine
      differences within 'Asian' subgroups according to duration of residence. DESIGN:
      Nutrient intake data from 24 h diet recalls and data from the dietary habits
      questionnaire, anthropometry and biochemical analyses from the cross-sectional
      2008/09 Adult National Nutrition Survey in New Zealand were compared for
      participants categorized as SA, ESEA and NZEO. SUBJECTS: Adults aged 15 years and
      older (n 2995). SETTING: New Zealand households. RESULTS: SA were more likely to
      'never' eat red meat in comparison to NZEO (P<0.001) and among females also in
      comparison to ESEA (P<0.05). Intakes of fats and some micronutrients (riboflavin,
      vitamin B6, B12, Se) were lower among SA than NZEO (P<0.05). Lower intakes of Zn
      and vitamin B12 were reported by SA females compared with ESEA and NZEO females
      (P<0.05). A higher percentage of SA were obese using ethnic-specific cut-offs,
      had lower indices of Fe status and reported diagnosed diabetes compared with NZEO
      and ESEA. Recent SA male migrants had higher intakes of beta-carotene, vitamin C
      and Ca compared with long-term migrants (P<0.05). CONCLUSIONS: The results of the
      present study indicate that dietary habits, nutrient intakes, blood profile and
      body size differ significantly between Asian subgroups. It also provides some
      evidence for changes in dietary intakes according to duration of residence
      especially for SA males.

PMID- 24887435
TI  - Baltorussus total makeover: rejuvenation and sex change in an ancient parasitoid
      wasp lineage.
AB  - The Orussidae is a small and rare but phylogenetically important family of
      parasitoid wasps. The fossil record of the family is also very poor. Baltorussus
      velteni was described from Baltic amber from an allegedly female specimen. This
      and another recently discovered specimen are examined with microCT scanning and
      standard microscopy. We reveal that both the holotype and the new specimen are
      actually males. Furthermore, the results of the microCT scanning allow us to
      integrate the fossils in a morphological data set assembled for extant Orussidae.
      Phylogenetic analyses consistently retrieve Baltorussus as a separate basal
      lineage within the crown group, whereas two Cretaceous fossils are placed as stem
      group orussids and a Dominican amber fossil in an extant genus. Based on the
      positions of the fossils, we estimate that the extant Orussidae radiated in the
      mid-Cretaceous (approx. 100 Ma ago). This is considerably younger than a
      previously suggested Early Jurassic date (180 Ma ago), which was primarily based
      on biogeographic evidence. 

PMID- 24887434
TI  - Ginsenoside Rh1 potentiates dexamethasone's anti-inflammatory effects for chronic
      inflammatory disease by reversing dexamethasone-induced resistance.
AB  - INTRODUCTION: Acquired resistance to glucocorticoids constitutes a major clinical
      challenge, often overlooked in the search for compounds to improve the effect of
      classic steroids. We sought to unravel how a plant-original compound, ginsenoside
      Rh1, potentiates dexmethasone (DEX)'s potential anti-inflammation properties.
      METHODS: Ginsenoside Rh1 combined with DEX was applied in a short-term and long
      term treatment protocol for inflammation. Its potential mechanism on anti
      inflammation was explored. In addition, the effect of Rh1 on the side-effect
      induced by DEX was studied. Furthermore, the in vivo anti-inflammatory effects of
      Rh1 combined with DEX were evaluated in a collagen-induced arthritis (CIA) mice
      model. RESULTS: Ginsenoside Rh1 potentiates DEX's anti-inflammatory effects even
      after prolonged DEX treatment. Rh1 could improve the glucocorticoid receptor
      (GR)'s transrepression on nuclear factor kappa B (NF-kappaB) and transactivation
      on dual specificity protein phosphatase 1 (DUSP1), which is responsible for DEX's
      anti-inflammatory effects. Parallel Western blot assay and radioligand binding
      analysis revealed that Rh1 could increase the expression and binding of GR. This
      is in sharp contrast to DEX alone, showing a direct link among prolonged
      treatment, decreasing GR and the abolishment of anti-inflammation. Interestingly,
      Rh1 does not enhance the transactivation of glucocorticoid-responsive elements
      (GRE) driven genes - gluconeogenic enzyme glucose-6-phosphatase (G6P) and
      phosphoenolpyruvate carboxykinasee phosphatase (PEPCK) in primary mouse
      hepatocytes, a mechanism partly held accountable for the metabolic side-effects.
      Similar results were found in CIA mice. CONCLUSION: Rh1 could potentiate DEX's
      anti-inflammatory effects and does not cause a hyperglycemic side effect.
      Ginsenoside Rh1 combined with DEX may be a promising candidate treatment option
      for chronic inflammatory diseases in need of long-term immunosuppression
      therapies.

PMID- 24887436
TI  - Genome-wide survey and expression analysis of calcium-dependent protein kinase in
      Gossypium raimondii.
AB  - Calcium-dependent protein kinases (CDPKs) are one of the largest protein kinases
      in plants and participate in different physiological processes through regulating
      downstream components of calcium signaling pathways. In this study, 41 CDPK
      genes, from GrCPK1 to GrCPK41, were identified in the genome of the diploid
      cotton, Gossypium raimondii. The phylogenetic analysis indicated that all these
      genes were divided into four subgroups and members within the same subgroup
      shared conserved exon-intron structures. The expansion of GrCPKs family in G.
      raimondii was due to the segmental duplication events, and the analysis of Ka/Ks
      ratios implied that the duplicated GrCPKs had mainly undergone strong purifying
      selection pressure with limited functional divergence. The cold-responsive
      elements in promoter regions were detected in the majority of GrCPKs. The
      expression analysis of 11 selected genes showed that GrCPKs exhibited tissue
      specific expression patterns and the expression of GrCPKs were induced or
      repressed by cold treatment. These observations would lay an important foundation
      for functional and evolutionary analysis of CDPK gene family in Gossypium
      species. 

PMID- 24887437
TI  - Insulin resistance: regression and clustering.
AB  - In this paper we try to define insulin resistance (IR) precisely for a group of
      Chinese women. Our definition deliberately does not depend upon body mass index
      (BMI) or age, although in other studies, with particular random effects models
      quite different from models used here, BMI accounts for a large part of the
      variability in IR. We accomplish our goal through application of Gauss mixture
      vector quantization (GMVQ), a technique for clustering that was developed for
      application to lossy data compression. Defining data come from measurements that
      play major roles in medical practice. A precise statement of what the data are is
      in Section 1. Their family structures are described in detail. They concern
      levels of lipids and the results of an oral glucose tolerance test (OGTT). We
      apply GMVQ to residuals obtained from regressions of outcomes of an OGTT and
      lipids on functions of age and BMI that are inferred from the data. A bootstrap
      procedure developed for our family data supplemented by insights from other
      approaches leads us to believe that two clusters are appropriate for defining IR
      precisely. One cluster consists of women who are IR, and the other of women who
      seem not to be. Genes and other features are used to predict cluster membership.
      We argue that prediction with "main effects" is not satisfactory, but prediction
      that includes interactions may be. 

PMID- 24887439
TI  - The diagnostic accuracy of ultrasonography versus endoscopy for primary
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: To compare the accuracy of ultrasonography (US) with the current
      clinical standard of endoscopy for a diagnosis of nasopharyngeal carcinoma (NPC).
      METHODS: A total of 150 patients suspected of having NPC underwent US and
      endoscopy. A diagnosis was obtained from an endoscopic biopsy collected from each
      suspected tumor and was compared with a biopsy obtained from a normal
      nasopharynx. The diagnostic accuracy of US and endoscopy for NPC was evaluated
      using receiver operating curve (ROC) analysis performed by MedCalc Software.
      RESULTS: The sensitivity, specificity, and accuracy of US versus endoscopy for
      this cohort were 90.1%, 84.8%, and 87.3%for US, and 88.7%, 97.5%, and 93.3% for
      endoscopy, respectively. Both US and endoscopy exhibited good diagnostic accuracy
      for NPC with area under the curve (AUC) values of 0.929 and 0.938, respectively.
      However, this difference was not significant (Z = 0.36, P = 0.72). CONCLUSION: US
      is a useful tool for the detection of tumors in endoscopically suspicious
      nasopharynx tissues, and also for the detection of subclinical tumors in
      endoscopically normal nasopharynx tissues.

PMID- 24887438
TI  - Maternal experience with predation risk influences genome-wide embryonic gene
      expression in threespined sticklebacks (Gasterosteus aculeatus).
AB  - There is growing evidence for nongenetic effects of maternal experience on
      offspring. For example, previous studies have shown that female threespined
      stickleback fish (Gasterosteus aculeatus) exposed to predation risk produce
      offspring with altered behavior, metabolism and stress physiology. Here, we
      investigate the effect of maternal exposure to predation risk on the embryonic
      transcriptome in sticklebacks. Using RNA-sequencing we compared genome-wide
      transcription in three day post-fertilization embryos of predator-exposed and
      control mothers. There were hundreds of differentially expressed transcripts
      between embryos of predator-exposed mothers and embryos of control mothers
      including several non-coding RNAs. Gene Ontology analysis revealed biological
      pathways involved in metabolism, epigenetic inheritance, and neural proliferation
      and differentiation that differed between treatments. Interestingly, predation
      risk is associated with an accelerated life history in many vertebrates, and
      several of the genes and biological pathways that were identified in this study
      suggest that maternal exposure to predation risk accelerates the timing of
      embryonic development. Consistent with this hypothesis, embryos of predator
      exposed mothers were larger than embryos of control mothers. These findings point
      to some of the molecular mechanisms that might underlie maternal effects. 

PMID- 24887440
TI  - Psychometric evaluation of the internalized stigma of mental illness scale for
      patients with mental illnesses: measurement invariance across time.
AB  - BACKGROUND: The current investigation examined the psychometric properties of the
      Internalized Stigma of Mental Illness (ISMI) scale in a sample of patients with
      mental illness. In addition to the internal consistency, test-retest reliability,
      and concurrent validity that previous studies have tested for the ISMI, we
      extended the evaluation to its construct validity and measurement invariance
      using confirmatory factor analysis (CFA). METHODS: Three hundred forty-seven
      participants completed two questionnaires (i.e., the ISMI and the Depression and
      Somatic Symptoms Scale [DSSS]), and 162 filled out the ISMI again after 50.23+/
      31.18 days. RESULTS: The results of this study confirmed the frame structure of
      the ISMI; however, the Stigma Resistance subscale in the ISMI seemed weak. In
      addition, internal consistency, test-retest reliability, and concurrent validity
      were all satisfactory for all subscales and the total score of the ISMI, except
      for Stigma Resistance (alpha = 0.66; ICC = 0.52, and r = 0.02 to 0.06 with DSSS).
      Therefore, we hypothesize that Stigma Resistance is a new concept rather than a
      concept in internalized stigma. The acceptable fit indices supported the
      measurement invariance of the ISMI across time, and suggested that people with
      mental illness interpret the ISMI items the same at different times. CONCLUSION:
      The clinical implication of our finding is that clinicians, when they design
      interventions, may want to use the valid and reliable ISMI without the Stigma
      Resistance subscale to evaluate the internalized stigma of people with mental
      illness.

PMID- 24887441
TI  - As the egg turns: monitoring egg attendance behavior in wild birds using novel
      data logging technology.
AB  - Egg turning is unique to birds and critical for embryonic development in most
      avian species. Technology that can measure changes in egg orientation and
      temperature at fine temporal scales (1 Hz) was neither readily available nor
      small enough to fit into artificial eggs until recently. Here we show the utility
      of novel miniature data loggers equipped with 3-axis (i.e., triaxial)
      accelerometers, magnetometers, and a temperature thermistor to study egg turning
      behavior in free-ranging birds. Artificial eggs containing egg loggers were
      deployed in the nests of three seabird species for 1-7 days of continuous
      monitoring. These species (1) turned their eggs more frequently (up to 6.5 turns
      h(-1)) than previously reported for other species, but angular changes were often
      small (1-10 degrees  most common), (2) displayed similar mean turning rates (ca.
      2 turns h(-1)) despite major differences in reproductive ecology, and (3)
      demonstrated distinct diurnal cycling in egg temperatures that varied between 1.4
      and 2.4  degrees C. These novel egg loggers revealed high-resolution, three
      dimensional egg turning behavior heretofore never measured in wild birds. This
      new form of biotechnology has broad applicability for addressing fundamental
      questions in avian breeding ecology, life history, and development, and can be
      used as a tool to monitor birds that are sensitive to disturbance while breeding.

PMID- 24887443
TI  - Single-port access laparoscopic surgery in gynecologic oncology: outcomes and
      feasibility.
AB  - OBJECTIVES: Single-port access laparoscopic surgery (SPALS) is supposed to
      simplify and improve the outcomes of current multiport laparoscopic procedures.
      This retrospective study was performed to assess the actual outcomes of SPALS in
      2 simple gynecological oncology procedures, namely, diagnostic laparoscopy and
      bilateral adnexectomy. METHODS: We conducted a retrospective monocentric study.
      Case files of only those women who underwent bilateral adnexectomies and
      diagnostic and/or staging laparoscopy were studied with respect to the operative
      room time, intraoperative and postoperative complications, postoperative pain,
      and lengths of hospital stays. The main objective was to assess the feasibility
      and utility of SPALS surgery in gynecology. The secondary objective was to
      compare this group with a cohort of patients with multiport conventional
      laparoscopic surgery (MPCLS) performed during the same period. RESULTS: From
      December 2009 to March 2013, there were 134 patients who underwent these 2
      procedures. Eighty adnexectomies were performed, 41 by SPALS and 39 by MPCLS.
      Fifty-four diagnostic laparoscopies were performed, with 27 patients in each
      group. In the group of adnexectomies, operative time was significantly lower in
      SPALS compared with MPCLS (36 vs 59 minutes, P < 10) and also compared with the
      postoperative stay (1 vs 2.2 nights, P < 10). By contrast, no significant
      difference was observed between the 2 methods of access in all the parameters
      studied in the group of diagnostic laparoscopies. CONCLUSIONS: Our experience
      demonstrates that SPALS is feasible and safe for simple gynecological procedures.
      This approach may result in a smooth postoperative course and shorter hospital
      stay and can thus be promoted to a day care procedure.

PMID- 24887442
TI  - Improving referral for genetic risk assessment in ovarian cancer using an
      electronic medical record system.
AB  - OBJECTIVE: We sought to evaluate an electronic referral form to increase referral
      for genetic risk assessment of women with newly diagnosed epithelial ovarian
      cancer. METHODS: A form summarizing referral for genetic counseling for women
      with ovarian cancer was introduced into the electronic medical record allowing
      gynecologic oncologists to electronically submit a request for genetic services.
      Analysis compared patient and provider characteristics for women newly diagnosed
      with ovarian, fallopian tube, and primary peritoneal cancer referred 1 year
      before and after introducing the form. All patients were seen in a single fee-for
      service university-based cancer center clinic. RESULTS: There were 86 newly
      diagnosed ovarian cancer patients seen before and 83 seen after the introduction
      of the electronic referral form. Most lived in the metropolitan area and had
      stage III to IV disease, serous histology, a documented family history, and a
      treating oncologist who was less than 10 years from completion of fellowship.
      Postintervention referral rates increased from 17% to 30% (P = 0.053). Factors
      best predicting referral were whether the patient was seen after the intervention
      (P = 0.009), resided in the metropolitan area (P = 0.006), and had been
      identified as at high hereditary risk (P < 0.0001). Sixty percent of the referred
      patients participated in counseling. There were no differences in baseline
      characteristics of the referred patients before and after the intervention.
      CONCLUSIONS: Referral rates increased with the introduction of an electronic
      medical record referral form suggesting that streamlining the physician referral
      process might be effective at increasing referrals for cancer genetic risk
      assessment.

PMID- 24887444
TI  - Use of titanium spiral tacks for long-term oophoropexy before pelvic irradiation.
AB  - BACKGROUND: Ovarian transposition before planned pelvic irradiation can preserve
      ovarian function in young patients with pelvic malignancies. The transposed
      ovaries are fixed to the posterolateral abdominal wall. We described the use of a
      titanium spiral tack as a fixation device and compared it with other methods of
      oophoropexy. METHODS: Medical and surgical records of all consecutive patients
      who underwent oophoropexy in our institution between 2007 and 2013 were reviewed.
      Demographic and clinical data were summarized; follicle-stimulating hormone
      values, recorded; and imaging scans, reviewed. RESULTS: Oophoropexy was performed
      in 30 patients: 28 with cervical carcinomas and 2 with pelvic sarcomas. The
      procedure was done through laparoscopy in 13 patients and through laparotomy in
      17. Titanium spiral tack was used for ovarian fixation in 14 patients, Vicryl
      suturing in 14, and in 2 cases the ovaries were pulled up through a
      retroperitoneal tunnel and fixed to the peritoneum with sutures. Titanium spiral
      tack fixation took a few seconds to perform. There were no immediate
      intraoperative or postoperative complications. Ovarian function was preserved in
      15 patients (7/14 with spiral tack, 6/14 with sutures, and in both patients with
      retroperitoneal tunneling). Postoperative imaging results showed that all ovaries
      retained their extrapelvic location for a median period of 11.6 months (range,
      2.3-63 months). CONCLUSIONS: Spiral tack is a simple, reliable method for
      oophoropexy before pelvic irradiation. Its efficacy is comparable with that of
      suture fixation, with the added advantage of ultrashort operative time. It is
      therefore worth considering as an alternative to suturing.

PMID- 24887445
TI  - Implementing a multifaceted tailored intervention to improve nutrition adequacy
      in critically ill patients: results of a multicenter feasibility study.
AB  - INTRODUCTION: Tailoring interventions to address identified barriers to change
      may be an effective strategy to implement guidelines and improve practice.
      However, there is inadequate data to inform the optimal method or level of
      tailoring. Consequently, we conducted the PERFormance Enhancement of the Canadian
      nutrition guidelines by a Tailored Implementation Strategy (PERFECTIS) study to
      determine the feasibility of a multifaceted, interdisciplinary, tailored
      intervention aimed at improving adherence to critical care nutrition guidelines
      for the provision of enteral nutrition. METHODS: A before-after study was
      conducted in seven ICUs from five hospitals in North America. During a 3-month
      pre-implementation phase, each ICU completed a nutrition practice audit to
      identify guideline-practice gaps and a barriers assessment to identify obstacles
      to practice change. During a one day meeting, the results of the audit and
      barriers assessment were reviewed and used to develop a site-specific tailored
      action plan. The tailored action plan was then implemented over a 12-month period
      that included bi-monthly progress meetings. Compliance with the tailored action
      plan was determined by the proportion of items in the action plan that was
      completely implemented. We examined acceptability of the intervention through
      staff responses to an evaluation questionnaire. In addition, the nutrition
      practice audit and barriers survey were repeated at the end of the implementation
      phase to determine changes in barriers and nutrition practices. RESULTS: All five
      sites successfully completed all aspects of the study. However, their ability to
      fully implement all of their developed action plans varied from 14% to 75%
      compliance. Nurses, on average, rated the study-related activities and resources
      as 'somewhat useful' and a third of respondents 'agreed' or 'strongly agreed'
      that their nutrition practice had changed as a result of the intervention. We
      observed a statistically significant 10% (Site range -4.3% to -26.0%) decrease in
      overall barriers score, and a non-significant 6% (Site range -1.5% to 17.9%) and
      4% (-8.3% to 18.2%) increase in the adequacy of total nutrition from calories and
      protein, respectively. CONCLUSIONS: The multifaceted tailored intervention
      appears to be feasible but further refinement is warranted prior to testing the
      effectiveness of the approach on a larger scale. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01168128. Registered 21 July 2010.

PMID- 24887446
TI  - Purity and adulterant analysis of crack seizures in Brazil.
AB  - Cocaine represents a serious problem to society. Smoked cocaine is very addictive
      and it is frequently associated with violence and health issues. Knowledge of the
      purity and adulterants present in seized cocaine, as well as variations in drug
      characteristics are useful to identify drug source and estimate health impact. No
      data are available regarding smoked cocaine composition in most countries, and
      the smoked form is increasing in the Brazilian market. The purpose of the present
      study is to contribute to the current knowledge on the status of crack cocaine
      seized samples on the illicit market by the police of Sao Paulo. Thus, 404
      samples obtained from street seizures conducted by the police were examined. The
      specimens were macroscopically characterized by color, form, odor, purity, and
      adulterant type, as well as smoke composition. Samples were screened for cocaine
      using modified Scott test and thin-layer chromatographic (TLC) technique.
      Analyses of purity and adulterants were performed with gas chromatography
      equipped with flame ionization detector (GC-FID). Additionally, smoke composition
      was analyzed by GC-mass spectrometry (MS), after samples burning. Samples showed
      different colors and forms, the majority of which is yellow (74.0%) or white
      (20.0%). Samples free of adulterants represented 76.3% of the total. Mean purity
      of the analyzed drug was 71.3%. Crack cocaine presented no correlations between
      macroscopic characteristics and purity. Smoke analysis showed compounds found
      also in the degradation of diesel and gasoline. Therefore, the drug marketed as
      crack cocaine in Sao Paulo has similar characteristics to coca paste. High purity
      can represent a greater risk of dependency and smoke compounds are possibly
      worsening drug health impact. 

PMID- 24887447
TI  - The involvement of serotonin polymorphisms in autistic spectrum symptomatology.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are highly inherited developmental
      syndromes, resulting from a complex interaction between environmental and genetic
      factors. To date, only a limited number of genetic variants have been discovered
      with respect to autism, and their contribution to the development of the disorder
      has not been clearly determined. Investigation of specific autistic
      symptomatology may improve the chances of identifying related genes and may help
      to better understand these disorders. MATERIALS AND METHODS: We investigated the
      contribution of 80 genetic variants in 15 serotonin genes to ASD phenotypes
      [intelligence quotation (IQ), intellectual disability (ID) and language onset
      delay (LD)] in a cohort of 141 children and young adults (121 male patients and
      20 female patients, average age 14.5+/-5.1 years). RESULTS: Two polymorphisms in
      the HTR2B gene, rs10194776 and rs16827801, were associated with IQ (P=0.0004 and
      0.003, respectively), ID (P=0.02 and 0.03) and LD (P=0.04 and 0.004). Nominal
      associations were also detected between the ASD phenotypes investigated and 5
      HT2A, 5-HT4 and 5-HT6 genetic variants. CONCLUSION: Our study provides evidence
      of the contribution of serotonergic variants to IQ, ID and LD in ASD patients.

PMID- 24887448
TI  - The microinjection of a cannabinoid agonist into the accumbens shell induces
      anxiogenesis in the elevated plus-maze.
AB  - This study investigated the effect of a cannabinoid agonist injected into the
      shell region of the nucleus accumbens (nAcb shell) on anxiety-related behaviors.
      The animals (male Wistar rats) were unilaterally microinjected with either ACEA
      (arachidonyl-2'-chloroethylamide a CB1 receptor agonist) at doses of 0.005, 0.05
      or 0.5 pmol, or vehicle (ethanol 0.04% in saline 0.9%) and submitted to the
      elevated plus-maze (EPM), a pre-clinical test of anxiety. The data showed that
      rats microinjected with ACEA (0.05 pmol/0.2 MUl) into the nAcb shell exhibited
      decreased % open arm time and open arm entries in comparison with the control
      group, which is compatible with an anxiogenic-like effect. To rule out the
      hypothesis that spread of the drug into the ventricle was responsible for the
      observed anxiogenic effect, 0.05 pmol ACEA was injected into the lateral
      ventricle and shown not to alter the responses representative of fear/anxiety and
      locomotion. The locomotor activity was not changed at the dose of 0.05 pmol ACEA
      microinjected into the nAcb shell. The present data suggest that activation of
      cannabinoid receptors in the nAcb shell may modulate fear/anxiety in the EPM.

PMID- 24887449
TI  - Chronic fluoxetine treatment promotes submissive behavior in the territorial
      frog, Eleutherodactylus coqui.
AB  - Serotonin (5-HT) is an essential neurotransmitter for many physiological and
      behavioral processes. Clinically and experimentally 5-HT metabolism can be
      altered using a class of drugs known as selective serotonin reuptake inhibitors
      (SSRIs). SSRIs such as fluoxetine have proven effective tools for elevating 5-HT
      activity and are routinely utilized to study the role of 5-HT in aggressive
      behavior. The Puerto Rican coqui frog, Eleutherodactylus coqui, is a terrestrial
      amphibian that exhibits territoriality and paternal care. E. coqui have three
      different male behavioral modes, territorial (calling), non-calling, and
      paternal. Territorial male E. coqui aggressively maintain and defend territories
      by emitting advertisement calls. The objective of this study was to determine if
      the SSRI, fluoxetine, influences the establishment of the dominant (territorial)
      subordinate (non-calling) relationship in male E. coqui. Wild captured adult
      territorial male E. coqui were grouped into 16 pairs in semi-natural terraria.
      Pharmacological treatment consisted of injecting (IP) experimental frogs with 25
      MUl (10mg/kg fluoxetine) of a fluoxetine/saline solution while control males
      received IP injections of saline. Injections were administered every other day
      for 20 days while observations continued until 40 days. Results indicated
      significantly higher numbers of advertisement calls emitted from control males
      after 20, 30, and 40 days. Additional, 13 of 16 control males emitted
      significantly more advertisement calls and became the territorial male.
      Fluoxetine treatment significantly reduced advertisement calling and territorial
      behavior in E. coqui males. These findings demonstrate that in E. coqui the 5-HT
      system has profound influence on male territorial and social behavior.

PMID- 24887451
TI  - Serotonergic and noradrenergic systems are implicated in the antidepressant-like
      effect of ursolic acid in mice.
AB  - Ursolic acid (UA) is a natural pentacyclic triterpenoid carboxylic acid that
      exerts antidepressant-like effects in the tail suspension test (TST) and in the
      forced swimming test, and this effect was reported to be mediated by the
      dopaminergic system. Many studies show that currently available antidepressant
      agents have effects on multiple neurotransmitter systems which account for their
      efficacy. Therefore, this study was aimed at investigating the possible
      involvement of the serotonergic, noradrenergic, glutamatergic and opioid systems
      in the antidepressant-like effect of UA. To this end, several pharmacological
      agents were administered to verify their ability to influence the antidepressant
      like responses elicited by UA in the TST in mice. The open-field test was used to
      assess the locomotor activity. The results show that the pre-treatment of mice
      with rho-chlorophenylalanine (100mg/kg, i.p., 4 days) or alpha-methyl-rho
      tyrosine (100mg/kg, i.p.) but not with N-methyl-d-aspartate (0.1 pmol/mouse,
      i.c.v.) or naloxone (1mg/kg, i.p.), was able to prevent the antidepressant-like
      effect of UA (0.1mg/kg, p.o.). Sub-effective doses of fluoxetine (5mg/kg, p.o.)
      or reboxetine (2mg/kg, p.o.), but not ketamine (0.1mg/kg, i.p.) or MK-801 (0.001
      mg/kg, p.o.), was capable of potentiating the effect of a sub-effective dose of
      UA (0.001 mg/kg, p.o.) in the TST. None of the treatments affected locomotor
      activity. Altogether, the results show an involvement of the serotonergic and
      noradrenergic systems, but not the glutamatergic or opioid systems, in the
      antidepressant-like effect of UA.

PMID- 24887450
TI  - Cross-substitution of Delta9-tetrahydrocannabinol and JWH-018 in drug
      discrimination in rats.
AB  - Synthetic indole-derived cannabinoids, originally developed to probe cannabinoid
      CB1 and CB2 receptors, have become widely abused for their marijuana-like
      intoxicating properties. The present study examined the effects of indole-derived
      cannabinoids in rats trained to discriminate Delta(9)-tetrahydrocannabinol
      (Delta(9)-THC) from vehicle. In addition, the effects of Delta(9)-THC in rats
      trained to discriminate JWH-018 from vehicle were assessed. Adult male Sprague
      Dawley rats were trained to discriminate 3mg/kg Delta(9)-THC or 0.3mg/kg JWH-018
      from vehicle. JWH-018, JWH-073, and JWH-210 fully substituted in Delta(9)-THC
      trained rats and Delta(9)-THC substituted in JWH-018-trained rats. In contrast,
      JWH-320, an indole-derived cannabinoid without affinity for CB1 receptors, failed
      to substitute for Delta(9)-THC. Pre-treatment with 1mg/kg rimonabant
      significantly reduced responding on the JWH-018-associated lever in JWH-018
      trained rats. These results support the conclusion that the interoceptive effects
      of Delta(9)-THC and synthetic indole-derived cannabinoids show a large degree of
      overlap, which is predictive of their use for their marijuana-like intoxicating
      properties. Characterization of the extent of pharmacological differences among
      structural classes of cannabinoids, and determination of their mechanisms remain
      important goals. 

PMID- 24887452
TI  - Poor responses to interferon-beta treatment in patients with neuromyelitis optica
      and multiple sclerosis with long spinal cord lesions.
AB  - Interferon-beta (IFN-beta) treatment may not be effective in neuromyelitis optica
      (NMO). Whether the poor response to IFN-beta is related to long spinal cord
      lesions (LSCL) or the NMO disease entity itself is unclear. We evaluated the
      spinal cord involvement of patients with multiple sclerosis (MS) and NMO, as well
      as the response after receiving IFN-beta. Forty-nine MS and 21 NMO patients
      treated with IFN-beta for at least 2 years from 2002-2008 were enrolled in this
      study and the treatment response was analyzed 2 years post-treatment. In the
      study, spinal cord lesions were present in 57.1% (28/49) of the MS patients, of
      which 16.3% (8/49) presented spinal cord lesions longer than 3 vertebral segments
      (LSCL). Responses to IFN-beta treatment were seen in 69.3% (34/49) of all the MS
      cases, of which the appropriate response rates were 76.1% (16/21) in MS patients
      without spinal cord lesions and 37.5% (3/8) in patients with LSCL. Only 14.2%
      (3/21) of NMO patients responded to IFN-beta treatment. In conclusion, spinal
      cord lesion is common in MS patients in Taiwan. Both NMO and MS patients with
      LSCL had a poor response to IFN-beta treatment. NMO patients had a worse response
      to IFN-beta treatment than MS patients with LSCL, which shows that the crucial
      structural defect is something other than LSCL such as the elevated serum IL17
      level in NMO compared to MS. 

PMID- 24887453
TI  - Clade age and diversification rate variation explain disparity in species
      richness among water scavenger beetle (Hydrophilidae) lineages.
AB  - Explaining the disparity of species richness across the tree of life is one of
      the great challenges in evolutionary biology. Some lineages are exceptionally
      species rich, while others are relatively species poor. One explanation for
      heterogeneity among clade richness is that older clades are more species rich
      because they have had more time to accrue diversity than younger clades.
      Alternatively, disparity in species richness may be due to among-lineage
      diversification rate variation. Here we investigate diversification in water
      scavenger beetles (Hydrophilidae), which vary in species richness among major
      lineages by as much as 20 fold. Using a time-calibrated phylogeny and comparative
      methods, we test for a relationship between clade age and species richness and
      for shifts in diversification rate in hydrophilids. We detected a single
      diversification rate increase in Megasternini, a relatively young and species
      rich clade whose diversity might be explained by the stunning diversity of
      ecological niches occupied by this clade. We find that Amphiopini, an old clade,
      is significantly more species poor than expected, possibly due to its restricted
      geographic range. The remaining lineages show a correlation between species
      richness and clade age, suggesting that both clade age and variation in
      diversification rates explain the disparity in species richness in hydrophilids.
      We find little evidence that transitions between aquatic, semiaquatic, and
      terrestrial habitats are linked to shifts in diversification rates. 

PMID- 24887454
TI  - Diazoxide protects against doxorubicin-induced cardiotoxicity in the rat.
AB  - AIM: Chemotherapy with doxorubicin is limited by cardiotoxicity. Free radical
      generation and mitochondrial dysfunction are thought to contribute to doxorubicin
      induced cardiac failure. In this study we wanted to investigate if opening of
      mitochondrial KATP-channels by diazoxide is protective against doxorubicin
      cardiotoxicity, and if 5-hydroxydecanoate (5-HD), a selective mitochondrial KATP
      channel antagonist, abolished any protection by this intervention. METHODS:
      Wistar rats were divided into 7 groups (n = 6) and followed for 10 days with 5
      intervention groups including the following treatments: (1) Diazoxide and
      doxorubicin, (2) diazoxide and 5-hydroxydecanoate (5-HD), (3) 5-HD and
      doxorubicin, (4) diazoxide and saline and (5) 5-HD and saline. On day 1, 3, 5 and
      7 the animals received intraperitoneal (i.p.) injections with 10 mg/kg diazoxide
      and/or 40 mg/kg 5-HD, 30 minutes before i.p. injections with 3.0 mg/kg
      doxorubicin. One control group received only saline injections and the other
      control group received saline 30 minutes prior to 3.0 mg/kg doxorubicin. On day
      10 the hearts were excised and Langendorff-perfused. Cardiac function was
      assessed by an intraventricular balloon and biochemical effects by release of
      hydrogen peroxide (H2O2) and troponin-T (TnT) in effluate from the isolated
      hearts, and by myocardial content of doxorubicin. RESULTS: Doxorubicin treatment
      produced a significant loss in left ventricular developed pressure (LVDP) (p <
      0.05) and an increase in both H2O2 and TnT release in effluate (p < 0.05).
      Diazoxide significantly attenuated the decrease in LVDP (p < 0.05) and abolished
      the increased release of H2O2 and TnT (p < 0.05). 5-HD abolished the effects of
      pretreatment with diazoxide, and these effects were not associated with reduced
      myocardial accumulation of doxorubicin. CONCLUSIONS: Pretreatment with diazoxide
      attenuates doxorubicin-induced cardiac dysfunction in the rat, measured by
      physiological indices and TnT and H2O2 in effluate from isolated hearts. The
      effect could be mediated by opening of mitochondrial KATP-channels, reduced
      doxorubicin-associated free radical generation and decreased cardiomyocyte
      damage. Diazoxide represents a promising protective intervention against
      doxorubicin-induced acute cardiotoxicity.

PMID- 24887455
TI  - Safety and effectiveness of antiretroviral therapies for HIV-infected women and
      their infants and children: protocol for a systematic review and network meta
      analysis.
AB  - BACKGROUND: Antiretroviral therapy reduces mother-to-child transmission of human
      immunodeficiency virus (HIV) during pregnancy, delivery, and breastfeeding.
      However, these agents have been associated with preterm birth, anemia and low
      birth weight. We aim to evaluate the comparative safety and effectiveness of the
      use of antiretroviral drugs among HIV-infected women and the effects on their
      infants and children through a systematic review and network meta-analysis.
      METHODS/DESIGN: Studies examining the effects of six antiretroviral drug classes
      (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse
      transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion
      inhibitors, co-receptor inhibitors) administered to HIV-infected pregnant women
      will be included. We will include randomized clinical trials (RCTs), quasi-RCTs,
      non-RCTs, controlled before-after, interrupted time series, cohort, registry, and
      case-control studies. No limitations will be imposed on publication status (that
      is, unpublished studies are eligible for inclusion), duration of follow-up, study
      conduct period, and language of dissemination. Comprehensive literature searches
      will be conducted in major electronic databases, including MEDLINE, EMBASE, and
      the Cochrane Central Register of Controlled Trials. Gray literature will be
      identified through searching dissertation databases, trial protocol registries,
      and conference abstracts.Two team members will independently screen all
      citations, full-text articles, and abstract data; conflicts will be resolved
      through discussion. The risk of bias and methodological quality will be appraised
      using appropriate tools (for example, Cochrane Collaboration's tool for assessing
      risk of bias, Newcastle-Ottawa Scale, and McMaster Quality Assessment Scale of
      Harms). If feasible and appropriate, we will conduct random effects meta
      analysis. Network meta-analysis will be considered for outcomes with the greatest
      number of treatment comparisons available that fulfill network meta-analysis
      assumptions (for example, consistency of evidence between direct and indirect
      data, and low statistical heterogeneity between included studies).The primary
      effectiveness outcome is mother-to-child transmission of HIV, and the primary
      safety outcome is major congenital malformation (overall and specific types)
      among newborns of HIV-infected women. Secondary safety outcomes include
      stillbirths, infant/child death, preterm delivery, overall and specific minor
      congenital malformations, and small for gestational age infants. DISCUSSION: Our
      systematic review will be of utility to healthcare providers, policy-makers, and
      HIV-positive women regarding the use of antiretroviral drugs. TRIAL REGISTRATION:
      PROSPERO registry number: CRD42014009071.

PMID- 24887456
TI  - The political polarization of physicians in the United States: an analysis of
      campaign contributions to federal elections, 1991 through 2012.
AB  - IMPORTANCE: Few current data are available regarding the political behavior of
      American physicians as the number of female physicians has increased and the
      number of solo practitioners has decreased. OBJECTIVE: To analyze campaign
      contributions that physicians made from the 1991 to 1992 through the 2011 to 2012
      election cycles to Republican and Democratic candidates in presidential and
      congressional races and to partisan organizations, including party committees and
      super political action committees (Super PACs). DESIGN, SETTING, AND
      PARTICIPANTS: We explored partisan differences in physician contributions by sex,
      for-profit vs nonprofit practice setting, and specialty using multiple regression
      analysis. We studied the relation between the variation in the mean annual income
      across specialties and the mean percentage of physicians within each specialty
      contributing to Republicans. MAIN OUTCOMES AND MEASURES: Differences in
      contributions to Republicans and Democrats, for all physicians and for subgroups.
      RESULTS: Between the 1991 to 1992 and the 2011 to 2012 election cycles, physician
      campaign contributions increased from $20 million to $189 million, and the
      percentage of active physicians contributing increased from 2.6% to 9.4%. Of
      physicians who contributed during the study period, the mean percentage
      contributing to Republicans was 57% for men and 31% for women. Since 1996, the
      percentage of physicians contributing to Republicans has decreased, to less than
      50% in the 2007 to 2008 election cycle and again in the 2011 to 2012 election
      cycle. Contributions to Republicans in 2011 to 2012 were more prevalent among men
      vs women (52.3% vs 23.6%), physicians practicing in for-profit vs nonprofit
      organizations (53.2% vs 25.6%), and surgeons vs pediatricians (70.2% vs 22.1%).
      In 1991 to 1992, these contribution gaps were smaller: for sex, 54.5% vs 30.9%;
      for organizations, 54.2% vs 40.0%; and for specialty, 65.5% vs 32.7%. The
      percentage of physicians contributing to Republicans across specialties
      correlated 0.84 with the mean log earnings of each specialty; specialties with
      higher mean earnings had higher percentages of physicians contributing to
      Republicans. CONCLUSIONS AND RELEVANCE: Between 1991 and 2012, the political
      alignment of US physicians shifted from predominantly Republican toward the
      Democrats. The variables driving this change, including the increasing percentage
      of female physicians and the decreasing percentage of physicians in solo and
      small practices, are likely to drive further changes.

PMID- 24887459
TI  - Ready! Fire! Aim! Firearm safety is every physician assistant's job.

PMID- 24887460
TI  - It's time for an international congress of physician assistants.

PMID- 24887461
TI  - New drug information.

PMID- 24887462
TI  - Why won't this rash respond to treatment?

PMID- 24887458
TI  - Relationship between HER2 expression and efficacy with first-line trastuzumab
      emtansine compared with trastuzumab plus docetaxel in TDM4450g: a randomized
      phase II study of patients with previously untreated HER2-positive metastatic
      breast cancer.
AB  - INTRODUCTION: The purpose of this study was to retrospectively explore the
      relationship between human epidermal growth factor receptor 2 (HER2) messenger
      RNA (mRNA) expression and efficacy in patients receiving trastuzumab plus
      docetaxel (HT) or trastuzumab emtansine (T-DM1). METHODS: Patients with HER2
      positive, locally advanced or metastatic breast cancer (MBC) were randomly
      assigned to HT (n=70) or T-DM1 (n=67). HER2 status was assessed locally using
      immunohistochemistry or fluorescence in situ hybridization and confirmed
      retrospectively by central testing. HER2 mRNA expression was assessed using
      quantitative reverse transcriptase polymerase chain reaction. RESULTS: HER2 mRNA
      levels were obtained for 116/137 patients (HT=61; T-DM1=55). Median pretreatment
      HER2 mRNA was 8.9. The risk of disease progression in the overall population was
      lower with T-DM1 than with HT (hazard ratio (HR)=0.59; 95% confidence interval
      (CI) 0.36 to 0.97). This effect was more pronounced in patients with HER2
      mRNA>=median (HR=0.39; 95% CI 0.18 to 0.85) versus <median (HR=0.85; 95% CI 0.44
      to 1.67). In the T-DM1 arm, median progression-free survival (PFS) was not
      reached in patients with HER2 mRNA>=median and was 10.6 months in patients with
      HER2 mRNA<median. In the HT arm, PFS was 8.8 versus 9.8 months in patients with
      HER2 mRNA>=median versus<median, respectively. The effect of HER2 mRNA expression
      on objective response rates was less pronounced. CONCLUSIONS: This exploratory
      analysis suggests that while overall, patients with HER2-positive MBC show
      improved PFS with T-DM1 relative to HT, the effect is enhanced in patients with
      tumor HER2 mRNA >= median. TRIAL REGISTRATION: ClinicalTrials.gov NCT00679341.

PMID- 24887457
TI  - Transient expression of Bcl6 is sufficient for oncogenic function and induction
      of mature B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be
      separated into two subtypes based upon molecular features with similarities to
      germinal centre B-cells (GCB-like) or activated B-cells (ABC-like). Here we
      identify gain of 3q27.2 as being significantly associated with adverse outcome in
      DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6
      oncogene, but does not alter BCL6 transcript levels or target-gene repression.
      Separately, we identify expression of BCL6 in a subset of human haematopoietic
      stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by 'hit
      and-run' oncogenesis. We model this hit-and-run mechanism by transiently
      expressing Bcl6 within murine HSPCs, and find that it causes mature B-cell
      lymphomas that lack Bcl6 expression and target-gene repression, are
      transcriptionally similar to post-GCB cells, and show epigenetic changes that are
      conserved from HSPCs to mature B-cells. Together, these results suggest that BCL6
      may function in a 'hit-and-run' role in lymphomagenesis. 

PMID- 24887463
TI  - A day in the life.

PMID- 24887464
TI  - H1N1 in perspective: the clinical impact of a novel influenza A virus.

PMID- 24887465
TI  - Bilateral shoulder pain developing after a hypoglycemic seizure.

PMID- 24887466
TI  - Dermatology diagnoses among rural and urban physician assistants.
AB  - OBJECTIVES: Dermatology is not heavily covered in the curricula of physician
      assistant (PA) programs or on the certification examination, even though patient
      visits to PAs for skin complaints are very common. If significant on-the-job
      training is thus required for dermatology care, then practice setting differences
      likely impact the quality of that informal training. This study sought to
      identify differences in the ability of rural and urban PAs to diagnose skin
      disorders. METHODS: An Internet-based survey of rural and urban primary care PAs
      (n = 295) was conducted. The survey collected demographic information and
      provided case scenarios with questions related to diagnosis of a skin disease or
      complication. RESULTS: Average quiz score was higher for rural PAs than for urban
      PAs (61.6% versus 55.4%, P = .024). Rural PAs more commonly treated the majority
      of their patients seen for skin complaints. Rural PAs reported a greater comfort
      level in diagnosing and treating skin disease than did urban PAs (91% versus 80%,
      P < .05). Both groups referred a comparable percentage of patients to skin
      specialists. Regression analysis identified several factors that accounted for
      the ability to predict success scores for both the rural (P < .05) and urban (P <
      .05) groups. CONCLUSIONS: The stronger overall ability of rural PAs to diagnose a
      variety of skin diseases is likely impacted by the higher number of dermatologic
      cases they see. PA educators should re-evaluate the curricula devoted to skin
      conditions and consider elective opportunities for students with an interest in a
      dermatology career.

PMID- 24887467
TI  - Common signs and symptoms, and a diagnosis that is often overlooked.

PMID- 24887468
TI  - A new verdict for hormone therapy: safe for younger women.

PMID- 24887470
TI  - What's new in .... HIV/AIDS treatment IRIS complicates recovery of immune status.

PMID- 24887471
TI  - Piecing together confusing symptoms.

PMID- 24887472
TI  - Evaluating the patient with a measure of equanimity.

PMID- 24887474
TI  - The ethics of using placebos for diagnosis and treatment in clinical practice.

PMID- 24887475
TI  - An immigrant with fever, chills, and pleural effusion.

PMID- 24887476
TI  - Case of the month.

PMID- 24887477
TI  - Elevated pleural effusion IL-17 is a diagnostic marker and outcome predictor in
      lung cancer patients.
AB  - BACKGROUND: Interleukin 17 (IL-17) is a proinflammatory cytokine produced mainly
      by CD4(+) T-lymphocytes and may be important in tumor cell growth and
      progression. In this study, we aimed to evaluate the diagnostic and prognostic
      value of pleural effusion levels of IL-17 in lung cancer patients with malignant
      pleural effusion (MPE). METHODS: Pleural effusion samples were collected from 78
      lung cancer patients with MPE and from 45 patients with nonmalignant pleural
      effusion. Pleural fluid concentrations of IL-17 were measured by using enzyme
      linked immunosorbent assays. RESULTS: Malignant effusion exhibited higher IL-17
      levels than nonmalignant effusion (20.49 +/- 5.27 pg/ml vs. 13.16 +/- 2.25 pg/ml;
      P < 0.01). Lung cancer patients with pleural fluid IL-17 levels below 15 pg/ml
      had longer overall survival than those patients with higher levels (10.8 months
      vs. 4.7 months; P < 0.05). On the basis of multivariate analysis, we found that
      pleural fluid IL-17 level was an independent prognostic factor in lung cancer
      patients with MPE. CONCLUSIONS: Measurement of IL-17 levels might be a useful
      diagnostic and prognostic test for lung cancer patients with MPE.

PMID- 24887478
TI  - Design and synthesis of lipid-coupled inositol 1,2,3,4,5,6-hexakisphosphate
      derivatives exhibiting high-affinity binding for the HIV-1 MA domain.
AB  - The precursor of Gag protein (Pr55(Gag)) of human immunodeficiency virus, the
      principal structural component required for virus assembly, is known to bind d
      myo-phosphatidylinositol 4,5-bisphosphate (PIP2). The N-terminus of Pr55(Gag),
      the MA domain, plays a critical role in the binding of Pr55(Gag) to the plasma
      membrane. Herein, we designed and synthesized myo-phosphatidylinositol 2,3,4,5,6
      pentakisphosphate (PIP5) derivatives comprising highly phosphorylated inositol
      and variously modified diacylglycerol to examine the MA-binding properties. The
      inositol moiety was synthesized starting with myo-inositol and assembled with a
      hydrophobic glycerol moiety through a phosphate linkage. The Kd value for MA
      binding of the PIP5 derivative 2 (Kd = 0.25 MUM) was the lowest (i.e., highest
      affinity) of all derivatives, i.e., 70-fold lower than the Kd for the PIP2
      derivative 1 (Kd = 16.9 MUM) and 100-fold lower than the Kd for IP6 (Kd = 25.7
      MUM), suggesting the possibility that the PIP5 derivative blocks Pr55(Gag)
      membrane binding by competing with PIP2 in MA-binding.

PMID- 24887479
TI  - Factors influencing quality of life and disease severity in Hungarian children
      and young adults with cystic fibrosis.
AB  - BACKGROUND: The aim of our study was to evaluate factors affecting cystic
      fibrosis (CF) patients' health-related quality of life (HRQoL) and to assess the
      level of agreement on HRQol between children and their parents. METHODS: Fifty
      nine patients (mean age: 14.03 +/- 4.81 years) from 5 Hungarian CF centres
      completed the survey. HRQoL was measured using The Cystic Fibrosis Questionnaire
      Revised (CFQ-R). Parents were asked to fill out a questionnaire about their
      smoking habits, educational level and history of chronic illness. Disease
      severity was assessed using the physician-reported Shwachman-Kulczycki (SK) score
      system. Spirometry, Body Mass Index (BMI) percentile (pc), hospitalisation and
      Pseudomonas aeruginosa (PA) infection were examined as physiologic parameters of
      CF, and the impact of these factors on HRQoL was assessed. A multivariate
      regression analysis was performed to identify the most important factors
      affecting HRQoL. The level of significance was set to 0.05. RESULTS: Passive
      smoking and parental educational level and chronic diseases status did not have a
      significant impact on the patients' HRQoL (p > 0.05). Significantly lower SK
      scores and spirometry values were found in low BMI pc patients (p < 0.001), in
      hospitalised (p < 0.01) and in PA-infected patients (p < 0.01), than in the
      adequate-weight, non-hospitalised and PA culture-negative subgroup. Lower CFQ-R
      scores were detected in hospitalised patients than in non-hospitalised patients
      in their Physical functioning domain. PA-infected patients had HRQoL scores that
      were significantly worse in the Body image (p < 0.01) and Respiratory symptoms (p
      < 0.05) domains than the PA culture-negative patients. Patients with a low BMI pc
      (<25th BMI pc) had significantly lower scores in the Eating, Body image and
      Treatment burden domains, than the adequate-weight patients (>25th BMI pc) (p <
      0.01). A strong child-parent agreement was found in the Physical functioning
      domain (r = 0.77, p < 0.01). CONCLUSIONS: Passive smoking, parental educational
      level and chronic diseases of parents do not affect the HRQoL of CF patients. In
      contrast, hospitalisation, PA infection and malnutrition have a significant and
      negative impact on patients' HRQoL and the clinical severity of the disease.
      Parents and children were consistent in their scoring of symptoms and behaviours
      that were observable.

PMID- 24887480
TI  - The flavonoid (-)-epicatechin affects cytoskeleton proteins and functions in
      Entamoeba histolytica.
AB  - Human amoebiasis is an intestinal disease with a global distribution. Due to
      reports of parasite resistance or susceptibility reduction to metronidazole
      treatment, there is a renewed interest for the search of new molecules with
      antiamoebic activity. The flavonoid (-)-epicatechin that was isolated from the
      Mexican medicinal plant Geranium mexicanum HBK has an in vitro activity against
      E. histolytica trophozoites, however its molecular effects have been poorly
      documented. Using a proteomic approach based on two-dimensional gel
      electrophoresis and mass spectrometry (ESI-MS/MS) analysis, we evidenced that E.
      histolytica cytoskeleton proteins exhibit differential abundance in response to (
      )-epicatechin treatment. Moreover, functional assays revealed modification on
      pathogenic mechanisms associated with cytoskeleton functionality, namely,
      adhesion, migration, phagocytosis and cytolysis. Consequently, these data
      suggested that (-)-epicatechin could affect virulence properties of this human
      pathogen. BIOLOGICAL SIGNIFICANCE: This work contributes with some advances in
      the action mechanisms involved in the antiamoebic effect of the flavonoid (-)
      epicatechin. We found that this flavonoid has an unusual effect on trophozoites
      growth that is dependent of its concentration. Additionally, we reported that (-)
      epicatechin affects mainly amebic cytoskeleton proteins, which results in
      alteration on important virulence mechanisms, like adhesion, migration,
      phagocytosis and cytolysis. This study provides new knowledge about a potential
      alternative therapy directed to the treatment of amoebiasis.

PMID- 24887481
TI  - Activated protease receptor-2 induces GATA6 expression to promote survival in
      irradiated colon cancer cells.
AB  - BACKGROUND AND AIMS: The resistance to irradiation is common and a great drawback
      in the treatment of cancer with radiotherapy; the underlying mechanism is
      unclear. GATA binding protein 6 (GATA6) is associated with the pathogenesis of
      cancer. This study aims to investigate the role of GATA6 on compromising
      irradiation effect on HT55 and HT29 cells, 2 colorectal cancer cell lines.
      METHODS: Human colon cancer cell lines, HT55 and HT29 cells, were treated with
      irradiation in the culture. Apoptosis of HT55 and HT29 cells was determined by
      flow cytometry. The expression of PAR2 and GATA6 in HT55 and HT29 cells was
      analyzed by real time RT-PCR and Western blotting. The gene silence and gene over
      expression were employed to observe the effect of GATA6 on p53 expression in HT55
      and HT29 cells. RESULTS: The results showed that HT55 and HT29 cells expressed
      protease-activated receptor-2 (PAR2). Irradiation induced 38.6% HT55 cell and
      33.8% HT29 cell apoptosis, which reduced to 4.2% and 5.6%, respectively after
      activation of PAR2. Exposure to irradiation increased the expression of GATA6;
      the latter played a critical role in suppression of p53 expression in HT55 and
      HT29 cells. Inhibition of GATA6 significantly increased the effect of irradiation
      on HT55 and HT29 cells. CONCLUSIONS: Activation of PAR2 compromises the effect of
      irradiation on inducing colorectal cancer cell apoptosis, which can be prevented
      by inhibition of GATA6 expression.

PMID- 24887482
TI  - Single-molecule dynamics of site-specific labeled transforming growth factor type
      II receptors on living cells.
AB  - We achieved single-molecule imaging and tracking of the transforming growth
      factor type II receptor (TbetaRII) that was labeled by an organic dye via a
      genetically encoded unnatural amino acid (UAA) and the copper-free click
      chemistry. The stoichiometry, mobility and dimerization kinetics of individual
      TbetaRII molecules were determined. 

PMID- 24887483
TI  - Liquid chromatography-tandem mass spectrometric assay for eltrombopag in 50MUL of
      human plasma: a pharmacokinetic study.
AB  - Eltrombopag is a thrombopoietin receptor agonist, used in the treatment of
      thrombocytopenia. This paper describes a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) assay method for the determination of eltrombopag in
      human plasma samples using eltrombopag 13C4 as internal standard (IS). Analyte
      and the IS were extracted from 50MUL of human plasma using protein precipitation
      technique with no drying, evaporation and reconstitution steps. The
      chromatographic separation was achieved on a C18 column by using a mixture of
      10mM ammonium formate (pH3) and acetonitrile (10:90, v/v) as the mobile phase at
      a flow rate of 1.0mL/min. The linearity of the method was established in the
      concentration range 50.0-10007ng/mL with r(2)>=0.99. The intra-day and inter-day
      precision and accuracy results in four validation batches across five
      concentration levels were well within the acceptance limits. The proposed method
      was found to be applicable to pharmacokinetic studies. 

PMID- 24887484
TI  - Simultaneous determination of 7-O-succinyl macrolactin A and its metabolite
      macrolactin A in rat plasma using liquid chromatography coupled to tandem mass
      spectrometry.
AB  - 7-O-Succinyl macrolactin A (SMA) and its major metabolite macrolactin A (MA) are
      generated from Bacillus polyfermenticus KJS-2. Both substances show inhibitory
      effects on angiogenesis and cancer cell invasion. SMA in rat plasma is known to
      be relatively stable at room temperature, but MA was not detected due to its
      instability. Therefore, a stabilizer is required to accurately measure the
      substance in biological rat samples. In this study, NaF and eserine were examined
      to determine whether they could stabilize MA to allow for accurate measurement in
      rat plasma. We also developed a rapid and simple chromatographic method using
      tandem mass spectrometry (MS/MS) for the simultaneous determination of these
      compounds in rat plasma. After simple protein precipitation with acetonitrile
      including methaqualone (internal standard), the analytes were chromatographed on
      a Hilic column with a mobile phase of 10mM formic acid aqueous solution,
      methanol, and acetonitrile (15:15:70, v/v). The accuracy and precision of the
      assay were in accordance with FDA regulations for the validation of bioanalytical
      methods. This analytical method was successfully applied to monitor plasma
      concentrations of both compounds over time following intravenous administration
      of a salt form of SMA in rats. 

PMID- 24887485
TI  - Parents' food choice motives and their associations with children's food
      preferences.
AB  - OBJECTIVE: The objective was to investigate parents' motives for selecting foods
      for their children and the associations between these motives and children's food
      preferences. DESIGN: Cross-sectional survey. A modified version of the Food
      Choice Questionnaire was used to assess parents' food choice motives. Parents
      also reported children's liking/disliking of 176 food and beverage items on 5
      point Likert scales. Patterns of food choice motives were examined with
      exploratory principal component analysis. Associations between motives and
      children's food preferences were assessed with linear regression while one-way
      and two-way ANOVA were used to test for sociodemographic differences. SETTING:
      Two Australian cities. SUBJECTS: Parents (n 371) of 2-5-year-old children.
      RESULTS: Health, nutrition and taste were key motivators for parents, whereas
      price, political concerns and advertising were among the motives considered least
      important. The more parents' food choice for their children was driven by what
      their children wanted, the less children liked vegetables (beta =-0.27, P<0.01),
      fruit (beta=-0.19, P<0.01) and cereals (beta=-0.28, P<0.01) and the higher the
      number of untried foods (r=0.17, P<0.01). The reverse was found for parents'
      focus on natural/ethical motives (vegetables beta=0.17, P<0.01; fruit beta=0.17,
      P<0.01; cereals beta=0.14, P=0.01). Health and nutrition motives bordered on
      statistical significance as predictors of children's fruit and vegetable
      preferences. CONCLUSIONS: Although parents appear well intentioned in their
      motives for selecting children's foods, there are gaps to be addressed in the
      nature of such motives (e.g. selecting foods in line with the child's desires) or
      the translation of health motives into healthy food choices.

PMID- 24887486
TI  - 4sUDRB-seq: measuring genomewide transcriptional elongation rates and initiation
      frequencies within cells.
AB  - Although transcriptional elongation by RNA polymerase II is coupled with many RNA
      related processes, genomewide elongation rates remain unknown. We describe a
      method, called 4sUDRB-seq, based on reversible inhibition of transcription
      elongation coupled with tagging newly transcribed RNA with 4-thiouridine and high
      throughput sequencing to measure simultaneously with high confidence genome-wide
      transcription elongation rates in cells. We find that most genes are transcribed
      at about 3.5 Kb/min, with elongation rates varying between 2 Kb/min and 6 Kb/min.
      4sUDRB-seq can facilitate genomewide exploration of the involvement of specific
      elongation factors in transcription and the contribution of deregulated
      transcription elongation to various pathologies. 

PMID- 24887487
TI  - Expression patterns of QTL based and other candidate genes in Madhukar * Swarna
      RILs with contrasting levels of iron and zinc in unpolished rice grains.
AB  - BACKGROUND: Identifying QTLs/genes for iron and zinc in rice grains can help in
      biofortification programs. Genome wide mapping showed 14 QTLs for iron and zinc
      concentration in unpolished rice grains of F7 RILs derived from Madhukar *
      Swarna. One line (HL) with high Fe and Zn and one line (LL) with low Fe and Zn in
      unpolished rice were compared with each other for gene expression using qPCR. 7
      day old seedlings were grown in Fe+ and Fe- medium for 10 days and RNA extracted
      from roots and shoots to determine the response of 15 genes in Fe- conditions.
      RESULTS: HL showed higher upregulation than LL in shoots but LL showed higher
      upregulation than HL in roots. YSL2 was upregulated only in HL roots and YSL15
      only in HL shoots and both up to 60 fold under Fe- condition. IRT2 and DMAS1 were
      upregulated 100 fold and NAS2 1000 fold in HL shoot. NAS2, IRT1, IRT2 and DMAS1
      were upregulated 40 to 100 fold in LL roots. OsZIP8, OsNAS3, OsYSL1 and OsNRAMP1
      which underlie major Fe QTL showed clear allelic differences between HL and LL
      for markers flanking QTL. The presence of iron increasing QTL allele in HL was
      clearly correlated with high expression of the underlying gene. OsZIP8 and OsNAS3
      which were within major QTL with increasing effect from Madhukar were 8 fold and
      4 fold more expressed in HL shoot than in LL shoot. OsNAS1, OsNAS2, OsNAS3,
      OsYSL2 and OsYSL15 showed 1.5 to 2.5 fold upregulation in flag leaf of HL when
      compared with flag leaf of Swarna. CONCLUSION: HL and LL differed in root length,
      Fe concentration and expression of several genes under Fe deficiency. The major
      distinguishing genes were NAS2, IRT2, DMAS1, and YSL15 in shoot and NAS2, IRT1,
      IRT2, YSL2, and ZIP8 in roots. The presence of iron increasing QTL allele in HL
      at marker locus close to genes also increased upregulation in HL.

PMID- 24887488
TI  - Mutation and expression analysis of the IDH1, IDH2, DNMT3A, and MYD88 genes in
      colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the leading causes of death around the world.
      Its genetic mechanism was intensively investigated in the past decades with
      findings of a number of canonical oncogenes and tumor-suppressor genes such as
      APC, KRAS, and TP53. Recent genome-wide association and sequencing studies have
      identified a series of promising oncogenes including IDH1, IDH2, DNMT3A, and
      MYD88 in hematologic malignancies. However, whether these genes are involved in
      CRC remains unknown. In this study, we screened the hotspot mutations of these
      four genes in 305 CRC samples from Han Chinese by direct sequencing. mRNA
      expression levels of these genes were quantified by quantitative real-time PCR
      (RT-qPCR) in paired cancerous and paracancerous tissues. Association analyses
      between mRNA expression levels and different cancerous stages were performed.
      Except for one patient harboring IDH1 mutation p.I99M, we identified no
      previously reported hotspot mutations in colorectal cancer tissues. mRNA
      expression levels of IDH1, DNMT3A, and MYD88, but not IDH2, were significantly
      decreased in the cancerous tissues comparing with the paired paracancerous normal
      tissues. Taken together, the hotspot mutations of IDH1, IDH2, DNMT3A, and MYD88
      gene were absent in CRC. Aberrant mRNA expression of IDH1, DNMT3A, and MYD88 gene
      might be actively involved in the development of CRC. 

PMID- 24887490
TI  - Supplementation with three different macular carotenoid formulations in patients
      with early age-related macular degeneration.
AB  - PURPOSE: To investigate the impact of three different macular carotenoid
      formulations on macular pigment optical density and visual performance in
      subjects with early age-related macular degeneration. METHODS: Fifty-two subjects
      were supplemented and followed for 12 months, 17 of them were in intervention
      Group 1 (20 mg/day lutein and 2 mg/day zeaxanthin); 21 in Group 2 (10 mg/day meso
      zeaxanthin, 10 mg/day lutein, and 2 mg/day zeaxanthin); and 14 in Group 3 (17
      mg/day meso-zeaxanthin, 3 mg/day lutein, and 2 mg/day zeaxanthin). The macular
      pigment optical density was measured using customized heterochromatic flicker
      photometry, and visual function was assessed using corrected distance visual
      acuity and by letter contrast sensitivity. RESULTS: A statistically significant
      increase in the macular pigment optical density was observed at all measured
      eccentricities in Group 2 (P <= 0.005) and in Group 3 (P < 0.05, for all), but
      only at 1.75 degrees  in Group 1 (P = 0.018). Statistically significant (P <
      0.05) improvements in letter contrast sensitivity were seen at all spatial
      frequencies (except 1.2 cycles per degree) in Group 3, and at low spatial
      frequencies in Groups 1 and 2. CONCLUSION: Augmentation of the macular pigment
      optical density across its spatial profile and enhancements in contrast
      sensitivity were best achieved after supplementation with a formulation
      containing high doses of meso-zeaxanthin in combination with lutein and
      zeaxanthin.

PMID- 24887489
TI  - Timing of vasopressor initiation and mortality in septic shock: a cohort study.
AB  - INTRODUCTION: Despite recent advances in the management of septic shock,
      mortality remains unacceptably high. Earlier initiation of key therapies
      including appropriate antimicrobials and fluid resuscitation appears to reduce
      the mortality in this condition. This study examined whether early initiation of
      vasopressor therapy is associated with improved survival in fluid therapy
      refractory septic shock. METHODS: Utilizing a well-established database, relevant
      information including duration of time to vasopressor administration following
      the initial documentation of recurrent/persistent hypotension associated with
      septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the
      United States of America, and Saudi Arabia. The primary endpoint was survival to
      hospital discharge. Secondary endpoints were length of ICU and hospital stay as
      well as duration of ventilator support and vasopressor dependence. Analysis
      involved multivariate linear and logistic regression analysis. RESULTS: In total,
      8,640 patients met the definition of septic shock with time of
      vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for
      analysis. The overall unadjusted hospital mortality rate was 53%. Independent
      mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence
      interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS
      (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41),
      neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI,
      0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR
      1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute
      Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI,
      1.10 to 1.12) were also found to be significant independent correlates of
      mortality. After adjustment, only a weak correlation between vasopressor delay
      and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P
      <0.001). This weak effect was entirely driven by the group of patients with the
      longest delays (>14.1 hours). There was no significant relationship of
      vasopressor initiation delay to duration of vasopressor therapy (P = 0.313) and
      only a trend to longer duration of ventilator support (P = 0.055) among
      survivors. CONCLUSION: Marked delays in initiation of vasopressor/inotropic
      therapy are associated with a small increase in mortality risk in patients with
      septic shock.

PMID- 24887491
TI  - Delirium and high fever are associated with subacute motor deterioration in
      Parkinson disease: a nested case-control study.
AB  - BACKGROUND: In Parkinson disease (PD), systemic inflammation caused by
      respiratory infections such as pneumonia frequently occurs, often resulting in
      delirium in the advanced stages of this disease. Delirium can lead to cognitive
      and functional decline, institutionalization, and mortality, especially in the
      elderly. Inflammation causes rapid worsening of PD motor symptoms and signs,
      sometimes irreversibly in some, but not all, patients. PURPOSE: To identify
      factors associated with subacute motor deterioration in PD patients with systemic
      inflammation. METHODS: The association of clinical factors with subacute motor
      deterioration was analyzed by a case-control study. Subacute motor deterioration
      was defined as sustained worsening by one or more modified Hoehn and Yahr (H-Y)
      stages. Using multivariable logistic regression incorporating baseline
      characteristics (age, sex, PD duration, modified H-Y stage, dementia, and
      psychosis history) and statistically selected possible predictors (peak body
      temperature, duration of leukocytosis, and presence of delirium), the odds ratios
      for these factors were estimated as relative risks. RESULTS: Of 80 PD patients
      with systemic inflammation, 26 with associated subacute motor deterioration were
      designated as cases and the remainder as controls. In the 26 cases, 6 months
      after its onset the motor deterioration had persisted in 19 patients and resolved
      in four (three were lost for follow-up). Multivariable logistic regression
      analysis showed that delirium and body temperature are significantly associated
      with motor deterioration after systemic inflammation (P = 0.001 for delirium and
      P = 0.026 for body temperature), the adjusted odds ratios being 15.89 (95%
      confidence interval [CI]: 3.23-78.14) and 2.78 (95% CI: 1.13-6.83), respectively.
      CONCLUSIONS: In patients with PD and systemic inflammation, delirium and high
      body temperature are strong risk factors for subsequent subacute motor
      deterioration and such deterioration can persist for over 6 months.

PMID- 24887492
TI  - Human umbilical cord-derived mesenchymal stem cells do not undergo malignant
      transformation during long-term culturing in serum-free medium.
AB  - BACKGROUND: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are in
      the foreground as a preferable application for treating diseases. However, the
      safety of hUC-MSCs after long-term culturing in vitro in serum-free medium
      remains unclear. METHODS: hUC-MSCs were separated by adherent tissue culture. hUC
      MSCs were cultured in serum-free MesenCult-XF medium and FBS-bases DMEM complete
      medium. At the 1st, 3rd, 5th, 8th, 10th, and 15th passage, the differentiation of
      MSCs into osteogenic, chondrogenic, and adipogenic cells was detected, and MTT,
      surface antigens were measured. Tumorigenicity was analyzed at the 15th passage.
      Conventional karyotyping was performed at passage 0, 8, and 15. The telomerase
      activity of hUC-MSCs at passage 1-15 was analyzed. RESULTS: Flow cytometry
      analysis showed that very high expression was detected for CD105, CD73, and CD90
      and very low expression for CD45, CD34, CD14, CD79a, and HLA-DR. MSCs could
      differentiate into osteocytes, chondrocytes, and adipocytes in vitro. There was
      no obvious chromosome elimination, displacement, or chromosomal imbalance as
      determined from the guidelines of the International System for Human Cytogenetic
      Nomenclature. Telomerase activity was down-regulated significantly when the
      culture time was prolonged. Further, no tumors formed in rats injected with hUC
      MSCs (P15) cultured in serum-free and in serum-containing conditions. CONCLUSION:
      Our data showed that hUC-MSCs met the International Society for Cellular Therapy
      standards for conditions of long-term in vitro culturing at P15. Since hUC-MSCs
      can be safely expanded in vitro and are not susceptible to malignant
      transformation in serum-free medium, these cells are suitable for cell therapy.

PMID- 24887494
TI  - Reconciling pesticide reduction with economic and environmental sustainability in
      arable farming.
AB  - Reducing pesticide use is one of the high-priority targets in the quest for a
      sustainable agriculture. Until now, most studies dealing with pesticide use
      reduction have compared a limited number of experimental prototypes. Here we
      assessed the sustainability of 48 arable cropping systems from two major
      agricultural regions of France, including conventional, integrated and organic
      systems, with a wide range of pesticide use intensities and management (crop
      rotation, soil tillage, cultivars, fertilization, etc.). We assessed cropping
      system sustainability using a set of economic, environmental and social
      indicators. We failed to detect any positive correlation between pesticide use
      intensity and both productivity (when organic farms were excluded) and
      profitability. In addition, there was no relationship between pesticide use and
      workload. We found that crop rotation diversity was higher in cropping systems
      with low pesticide use, which would support the important role of crop rotation
      diversity in integrated and organic strategies. In comparison to conventional
      systems, integrated strategies showed a decrease in the use of both pesticides
      and nitrogen fertilizers, they consumed less energy and were frequently more
      energy efficient. Integrated systems therefore appeared as the best compromise in
      sustainability trade-offs. Our results could be used to re-design current
      cropping systems, by promoting diversified crop rotations and the combination of
      a wide range of available techniques contributing to pest management. 

PMID- 24887495
TI  - NGF and TERT co-transfected BMSCs improve the restoration of cognitive impairment
      in vascular dementia rats.
AB  - Vascular dementia (VaD) is a mental disorder caused by brain damage due to
      cerebrovascular disease, and incidence of VaD is rising. To date, there is no
      known effective cure for VaD, so effort in developing an effective treatment for
      VaD is of great importance. The differentiation plasticity of BMSCs, in
      conjunction with its weak immunogenicity, makes manipulated BMSCs an attractive
      strategy for disease treatment. However, BMSCs often display disabled
      differentiation, premature aging, and unstable proliferation, reducing their
      neuroprotective function. These problems may be caused by the lack of telomerase
      activity in BMSCs. Our results show that NGF-TERT co-transfected BMSCs have a
      better therapeutic effect than BMSCs lacking NGF and TERT expression,
      demonstrated by significant improvements in learning and memory in VaD rats. The
      underlying mechanism might be increased expression of NGF, TrkA and SYN in the
      hippocampal CA1 area, which has potential implication in advancing therapeutics
      for VaD. 

PMID- 24887496
TI  - Physical and social home environment in relation to children's overall and home
      based physical activity and sedentary time.
AB  - BACKGROUND: Given the obesity epidemic, it is critical to understand factors
      associated with youth physical activity and sedentary behavior at home, where
      youth spend significant time. We examined relationships between these child
      behaviors and home environment factors. METHODS: Data were obtained from 713
      children aged 6 to 11 in Washington and California 2007-2009. Multivariate
      regression analyses controlling for socio-demographics examined associations
      between parent-reported home environment factors and child's accelerometer
      measured moderate-to-vigorous physical activity (MVPA) and sedentary time,
      overall and at home, and parent-reported child screen time. RESULTS: Children
      averaged 47.2% of time at home, which included 43.6% and 46.4% of overall MVPA
      and sedentary behavior, respectively. Parental support for physical activity and
      having a basketball hoop were positively associated with MVPA and negatively
      associated with sedentary behavior. Combined parental support and a basketball
      hoop was associated with even higher MVPA. Children with fewer bedroom media
      devices and more fixed play equipment had lower overall sedentary behavior and
      screen time than either factor alone. Findings were similar regardless of weight
      status. CONCLUSIONS: Physical and social home environment variables, especially
      when combined, were related to more child MVPA and less sedentary behavior.
      Results support addressing multiple home environment factors in childhood obesity
      prevention.

PMID- 24887498
TI  - Synthesis of gold-cellobiose nanocomposites for colorimetric measurement of
      cellobiase activity.
AB  - Gold-cellobiose nanocomposites (GCNCs) were synthesized by reducing gold salt
      with a polysaccharide, cellobiose. Here, cellobiose acted as a controller of
      nucleation or stabilizer in the formation of gold nanoparticles. The obtained
      GCNCs were characterized with UV-visible spectroscopy; Zetasizer and Fourier
      transform infrared (FT-IR) spectrophotometer. Moreover, 6-Mercapto-1-hexanol
      (MCH) was modified on GCNCs, and the MCH-GCNCs were used to determine the
      cellobiase activity in compost extracts based on the surface plasmon resonance
      (SPR) property of MCH-GCNCs. The degradation of cellobiose on MCH-GCNCs by
      cellobiase could induce the aggregation, and the SPR absorption wavelength of MCH
      GCNCs correspondingly red shifted. Thus, the absorbance ratio of treated MCH
      GCNCs (A650/A520) could be used to estimate the cellobiase activity, and the
      probe exhibited highly sensitive and selective detection of the cellobiase
      activity with a wide linear from 3.0 to 100.0U L(-1) within 20 min. Meanwhile, a
      good linear relationship with correlation coefficient of R2=0.9976 was obtained.
      This approach successfully showed the suitability of gold nanocomposites as a
      colorimetric sensor for the sensitive and specific enzyme activity detection.

PMID- 24887497
TI  - Studies on the interaction between 9-fluorenylmethyl chloroformate and Fe3+ and
      Cu2+ ions: spectroscopic and theoretical calculation approach.
AB  - The interaction between 9-fluorenylmethyl chloroformate (FMOC-Cl) and Fe3+ and
      Cu2+ ions was investigated using fluorescence, UV/Vis absorption spectroscopies
      and theoretical calculation. The optical property of FMOC-Cl was studied in
      detail in absence and presence of various transition metal ions with particular
      affinity to Fe3+ and Cu2+ ions. With the fluorescence characteristic band
      centered at 307 and 315 nm for FMOC-Cl, the introduction of Fe3+ or Cu2+ ions
      leads to the fluorescence quenching of FMOC-Cl with different shift and
      intensities of two fluorescent bands. It allows us to differentiate between FMOC
      Cl and Fe3+ and Cu2+ ions interaction behavior. The study on fluorescent kinetics
      confirms that the fluorescence quenching of FMOC-Cl with Fe3+ and Cu2+ ions is
      based on the formation of non-fluorescent material, that is, static quenching.
      Further analyses of bond lengths, Mulliken atomic charges and the frontier
      orbital compositions for FMOC-Cl and its complexes with Fe3+ and Cu2+ ions were
      carried out. The theoretical calculations prove the fluorescence quenching
      originates from the formation of coordination bonds between the oxygen atom of
      the carbonyl group of FMOC-Cl and Fe3+ and Cu2+ ions. The commercially available
      FMOC-Cl can be used as excellent fluorescent probe toward Fe3+ and Cu2+ ions with
      high sensitivity.

PMID- 24887499
TI  - Computation and interpretation of vibrational spectra on the structure of
      Losartan using ab initio and Density Functional methods.
AB  - The solid phase FTIR and FT-Raman spectra of Losartan have been recorded in the
      region 400-4000 cm(-1). The spectra were interpreted in terms of fundamental
      modes, combination and overtone bands. The structure of the molecule was
      optimized and the structural characteristics were determined by Quantum chemical
      methods. The vibrational frequencies yield good agreement between observed and
      calculated values. The infrared and Raman spectra were also predicted from the
      calculated intensities. 1H and 13C NMR spectra were recorded and resonance
      chemical shifts of the molecule were calculated. UV-Visible spectrum of the
      compound was recorded in the region 200-600 nm and the electronic properties HOMO
      and LUMO energies calculated by TD-HF approach. NBO atomic charges of the
      molecules and second order perturbation theory analysis of Fock matrix also
      calculated and interpreted. The geometrical parameters, energies, harmonic
      vibrational frequencies, IR intensities, Raman intensities, and absorption
      wavelengths were compared with experimental and theoretical data of the molecule.

PMID- 24887500
TI  - Guest:host interactions of lidocaine and prilocaine with natural cyclodextrins:
      spectral and molecular modeling studies.
AB  - Inclusion complex formation of two local anesthetics drugs (lidocaine (LC) and
      prilocaine (PC)) with alpha- and beta-cyclodextrins (CDs) in aqueous solution
      were studied by absorption, fluorescence, time-resolved fluorescence and
      molecular modeling methods. The formation of inclusion complexes was confirmed by
      1H NMR, FTIR, differential scanning calorimetry, SEM, TEM and X-ray
      diffractometry. Both drugs formed 1:1 inclusion complex and exhibit biexponential
      decay in water whereas triexponential decay in the CD solution. Nanosized self
      aggregated particles of drug: CD complexes were found by TEM. Both experimental
      and theoretical studies revealed that the phenyl ring with the amide group of the
      drug is encapsulated in the hydrophobic CD nanocavity. Investigations of
      energetic and thermodynamic properties confirmed the stability of the inclusion
      complexes. van der Waals interactions are mainly responsible for enthalpy driven
      complex formation of LC and PC with CDs.

PMID- 24887501
TI  - Exploring type II microcalcifications in benign and premalignant breast lesions
      by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS).
AB  - The characteristics of type II microcalcifications in fibroadenoma (FB), atypical
      ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) breast tissues has
      been analyzed by the fingerprint features of Raman spectroscopy. Fresh breast
      tissues were first handled to frozen sections and then they were measured by
      normal Raman spectroscopy. Due to inherently low sensitivity of Raman scattering,
      Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS)
      technique was utilized. A total number of 71 Raman spectra and 70 SHINERS spectra
      were obtained from the microcalcifications in benign and premalignant breast
      tissues. Principal component analysis (PCA) was used to distinguish the type II
      microcalcifications between these tissues. This is the first time to detect type
      II microcalcifications in premalignant (ADH and DCIS) breast tissue frozen
      sections, and also the first time SHINERS has been utilized for breast cancer
      detection. Conclusions demonstrated in this paper confirm that SHINERS has great
      potentials to be applied to the identification of breast lesions as an auxiliary
      method to mammography in the early diagnosis of breast cancer. 

PMID- 24887502
TI  - A novel optical DNA biosensor for detection of trace amounts of mercuric ions
      using gold nanoparticles introduced onto modified glass surface.
AB  - In this work we report a DNA spectrophotometric biosensor for detection of Hg2+
      ions in which a pair of oligonucleotides with four thymine-thymine (T-T)
      mismatched bases was immobilized onto modified glass surface. Firstly, glass
      surface modified with 3-(mercaptopropyl) trimethoxysilane (MSPT) and gold nano
      particles respectively and then one oligonucleotide (P1) modified with hexanthiol
      at 5-terminal was immobilized on gold nano-particles via self-assembly and
      inserted in methylene blue. Methylene blue can intercalate on single strand DNA
      (ss-DNA) and its absorption peak can measure spectrophotometrically. Then the
      other oligonucleotide was able to hybridize with P1 by forming thymine-Hg2+
      thymine (T-Hg2+-T) complexes in the presence of Hg2+, and absorption signal of
      methylene blue reduced upon Hg2+ increasing concentration because inaccessibility
      of guanine base in DNA duplex. However, when Hg2+ was absent, the two
      oligonucleotides could not hybridize due to the T-T mismatched bases, and P2
      could not be fixed on the modified glass surface and any change in absorption
      peak of methylene blue takes place. The UV-Vis spectrum showed a linear
      correlation between the absorption peak of methylene blue and the concentration
      of Hg2+ over the range from 10 nM to 10 MUM (R2=0.9985) with a detection limit of
      6 nM. This spectrophotometric biosensor could be widely used for selective
      detection of Hg2+.

PMID- 24887503
TI  - Synthesis, spectroscopic studies, antimicrobial activities and antitumor of a new
      monodentate V-shaped Schiff base and its transition metal complexes.
AB  - Reaction of 4-aminoacetophenone and 4-bromobenzaldehyde in ethanol resulted in
      the formation of the monodentate V-shaped Schiff base (E)-1-(4-((4-bromo
      benzylidene)amino)phenyl)ethanone (L). Interaction of L with different di- and
      trivalent metal ions revealed disubstituted derivatives. The ligand and its
      complexes were characterized by elemental analysis, mass, IR and NMR
      spectrometry. Biological activities of the ligand and complexes against the
      Escherchia coli and Staphylococcus aureus bacterias, and the two fungus
      Aspergillus flavus and Candida albicans were screened. The cytotoxicity of the
      compounds were checked as antitumor agents on liver carcinoma cell line (HepG2).
      They exhibited in vitro broad range of antitumor activities towards the cell
      line; the [ZnL2(H2O)2](NO3)2 complex was stronger antitumor towards HepG2 cell
      line as well as two breast cancer cell lines (MCF7 and T47D) relative to cis
      platin. 

PMID- 24887504
TI  - Green synthesis, optical properties and catalytic activity of silver
      nanoparticles in the synthesis of N-monosubstituted ureas in water.
AB  - We report the green synthesis of silver nanoparticles by using Euphorbia
      condylocarpa M. bieb root extract for the synthesis of N-monosubstituted ureas in
      water. UV-visible studies show the absorption band at 420 nm due to surface
      plasmon resonance (SPR) of the silver nanoparticles. This reveals the reduction
      of silver ions (Ag+) to silver (Ago) which indicates the formation of silver
      nanoparticles (Ag NPs). This method has the advantages of high yields, simple
      methodology and easy work up.

PMID- 24887505
TI  - FT-IR and FT-Raman spectra of 5-fluoroorotic acid with solid state simulation by
      DFT methods.
AB  - FT-Raman and FT-IR studies of the biomolecule 5-fluoroorotic acid in the solid
      state were carried out. The unit cell found in the crystal was simulated as a
      tetramer form by density functional calculations. They were performed to clarify
      wavenumber assignments of the experimental observed bands in the spectra.
      Correlations with the molecule of uracil were made, and specific scale equations
      were employed to scale the wavenumbers of 5-fluoroorotic acid. Good reproduction
      of the experimental wavenumbers is obtained and the % error is very small in the
      majority of the bands. This fact confirms our simplified solid state model. The
      molecular structure was fully optimized using DFT and MP2 methods. The relative
      stability of both the syn and anti conformations was investigated, and the anti
      form was found to be slightly more stable, by 7.49 kJ/mol at the MP2 level. The
      structures of all possible tautomeric forms were determined. The keto-form
      appeared as the most stable one. The NBO atomic charges and several thermodynamic
      parameters were also calculated.

PMID- 24887506
TI  - Simultaneous determination of some anti-hypertensive drugs in their binary
      mixture by novel spectrophotometric methods.
AB  - Three simple, accurate and precise spectrophotometric methods manipulating ratio
      spectra were developed and validated for simultaneous determination of Irbesartan
      (IRB) and Hydrochlorothiazide (HCT) without prior separation namely; ratio
      subtraction coupled with constant multiplication (RS-CM), ratio difference (RD)
      and constant center (CC). The accuracy, precision and linearity ranges of the
      proposed methods were determined, and the methods were validated and the
      specificity was assessed by analyzing synthetic mixtures containing the cited
      drugs. The three methods were applied for the determination of the cited drugs in
      tablets and the obtained results were statistically compared with each other and
      with those of official methods. The comparison showed that there is no
      significant difference between the proposed methods and the official methods
      regarding both accuracy and precision. 

PMID- 24887507
TI  - Molecular structure investigation of organic cocrystals of 1,10-phenanthroline
      5,6-dione with aryloxyacetic acid: a combined experimental and theoretical study.
AB  - Two organic cocrystals namely, 1,10-phenanthroline-5,6-dione:2-naphthoxyacetic
      acid [(phendione)(2-naa)] (1) and 1,10-phenanthroline-5,6-dione:2
      formylphenoxyacetic acid [(phendione)(2-fpaa)] (2) were synthesized and studied
      by single crystal XRD, FT-IR, NMR, thermogravimetric, and powder X-ray
      diffraction analysis. The molecular properties of cocrystals were studied using
      density functional theory (DFT), basis set B3LYP/6-31G(d,p). Both cocrystals are
      stabilized through intermolecular hydrogen bonding (OH?N). The total electron
      density and molecular electrostatic potential surfaces of the cocrystals were
      constructed by NBO analysis using B3LYP/6-31G(d,p) method to display the
      electrostatic potential (electron+nuclei) distribution. The energy gap between
      HOMO and LUMO was measured for both cocrystals. 

PMID- 24887508
TI  - Development of a new catalase activity assay for biological samples using optical
      CUPRAC sensor.
AB  - A novel catalase activity assay was developed for biological samples (liver and
      kidney tissue homogenates) using a rapid and low-cost optical sensor-based
      'cupric reducing antioxidant capacity' (CUPRAC) method. The reagent, copper(II)
      neocuproine (Cu(II)-Nc) complex, was immobilized onto a cation-exchanger film of
      Nafion, and the absorbance changes associated with the formation of the highly
      colored Cu(I)-Nc chelate as a result of reaction with hydrogen peroxide (H2O2)
      was measured at 450 nm. When catalase was absent, H2O2 produced the CUPRAC
      chromophore, whereas catalase, being an effective H2O2 scavenger, completely
      annihilated the CUPRAC signal due to H2O2. Thus, the CUPRAC absorbance due to
      H2O2 oxidation concomitant with Cu(I)-Nc formation decreased proportionally with
      catalase. The developed sensor gave a linear response over a wide concentration
      range of H2O2 (0.68-78.6 MUM). This optical sensor-based method applicable to
      tissue homogenates proved to be efficient for low hydrogen peroxide
      concentrations (physiological and nontoxic levels) to which the widely used UV
      method is not accurately responsive. Thus, conventional problems of the UV method
      arising from relatively low sensitivity and selectivity, and absorbance
      disturbance due to gaseous oxygen evolution were overcome. The catalase findings
      of the proposed method for tissue homogenates were statistically alike with those
      of HPLC.

PMID- 24887510
TI  - Balancing the benefits and risks of empirical antibiotics for sinusitis: a
      teachable moment.

PMID- 24887509
TI  - Separable responses to error, ambiguity, and reaction time in cingulo-opercular
      task control regions.
AB  - The dorsal anterior cingulate (dACC), along with the closely affiliated anterior
      insula/frontal operculum, have been demonstrated to show three types of task
      control signals across a wide variety of tasks. One of these signals, a transient
      signal that is thought to represent performance feedback, shows greater activity
      to error than correct trials. Other work has found similar effects for
      uncertainty/ambiguity or conflict, though some argue that dACC activity is,
      instead, modulated primarily by other processes more reflected in reaction time.
      Here, we demonstrate that, rather than a single explanation, multiple information
      processing operations are crucial to characterizing the function of these brain
      regions, by comparing operations within a single paradigm. Participants performed
      two tasks in an fMRI experimental session: (1) deciding whether or not visually
      presented word pairs rhyme, and (2) rating auditorily presented single words as
      abstract or concrete. A pilot was used to identify ambiguous stimuli for both
      tasks (e.g., word pair: BASS/GRACE; single word: CHANGE). We found greater
      cingulo-opercular activity for errors and ambiguous trials than clear/correct
      trials, with a robust effect of reaction time. The effects of error and ambiguity
      remained when reaction time was regressed out, although the differences
      decreased. Further stepwise regression of response consensus (agreement across
      participants for each stimulus; a proxy for ambiguity) decreased differences
      between ambiguous and clear trials, but left error-related differences almost
      completely intact. These observations suggest that trial-wise responses in
      cingulo-opercular regions monitor multiple performance indices, including
      accuracy, ambiguity, and reaction time. 

PMID- 24887511
TI  - Trends in child and adolescent obesity prevalence according to socioeconomic
      position: protocol for a systematic review.
AB  - BACKGROUND: Obesity is a significant public health issue and is socially
      patterned, with greater prevalence of obesity observed in the most
      socioeconomically disadvantaged groups. Recent evidence suggests that the
      prevalence of childhood obesity is levelling off in some countries. However, this
      may not be the case across all socioeconomic strata. The aim of this review is to
      examine whether trends in child and adolescent obesity prevalence since 1990
      differ according to socioeconomic position in developed countries. METHODS: An
      electronic search will be conducted via Ovid Medline, Embase, Cumulative Index to
      Nursing and Allied Health Literature, Scopus and Cochrane Collaboration to
      identify articles that report trends in obesity prevalence in children and
      adolescents according to socioeconomic position. We will also search grey
      literature databases including the Virtual Library for Public Health and the
      System for Information on Grey Literature, as well as websites from relevant
      organisations. Articles that report on a series of cross sectional studies;
      describe one or more measure of obesity with data recorded at two or more time
      points since 1990; and report trends by at least one indicator of socioeconomic
      position will be included. Quality of included studies will be evaluated
      according to criteria that consider both internal and external validity.
      Descriptive analysis will be performed to examine trends since 1990 in childhood
      obesity prevalence according to socioeconomic position. DISCUSSION: The review
      will provide a picture of change over time in developed countries of childhood
      obesity prevalence across socioeconomic strata and identify whether changes in
      childhood obesity prevalence are experienced equally across socioeconomic groups.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014007625.

PMID- 24887512
TI  - Diversity and communities of foliar endophytic fungi from different
      agroecosystems of Coffea arabica L. in two regions of Veracruz, Mexico.
AB  - Over the past 20 years, the biodiversity associated with shaded coffee
      plantations and the role of diverse agroforestry types in biodiversity
      conservation and environmental services have been topics of debate. Endophytic
      fungi, which are microorganisms that inhabit plant tissues in an asymptomatic
      manner, form a part of the biodiversity associated with coffee plants. Studies on
      the endophytic fungi communities of cultivable host plants have shown variability
      among farming regions; however, the variability in fungal endophytic communities
      of coffee plants among different coffee agroforestry systems is still poorly
      understood. As such, we analyzed the diversity and communities of foliar
      endophytic fungi inhabiting Coffea arabica plants growing in the rustic
      plantations and simple polycultures of two regions in the center of Veracruz,
      Mexico. The endophytic fungi isolates were identified by their morphological
      traits, and the majority of identified species correspond to species of fungi
      previously reported as endophytes of coffee leaves. We analyzed and compared the
      colonization rates, diversity, and communities of endophytes found in the
      different agroforestry systems and in the different regions. Although the
      endophytic diversity was not fully recovered, we found differences in the
      abundance and diversity of endophytes among the coffee regions and differences in
      richness between the two different agroforestry systems of each region. No
      consistent pattern of community similarity was found between the coffee
      agroforestry systems, but we found that rustic plantations shared the highest
      number of morphospecies. The results suggest that endophyte abundance, richness,
      diversity, and communities may be influenced predominantly by coffee region, and
      to a lesser extent, by the agroforestry system. Our results contribute to the
      knowledge of the relationships between agroforestry systems and biodiversity
      conservation and provide information regarding some endophytic fungi and their
      communities as potential management tools against coffee plant pests and
      pathogens. 

PMID- 24887513
TI  - Dynamics of two multi-stemmed understory shrubs in two temperate forests.
AB  - A multi-stemmed growth form may be an important trait enabling the persistence of
      individual shrubs in the forest understory. With the aim of evaluating the role
      of multiple stems, neighbor competition and soil nutrients in shrub performance,
      we study the dynamics of two temperate multi-stemmed shrub species. We modeled
      stem growth and survival of Corylus mandshurica and Acer barbinerve in two
      temperate forests with differing structure in northeastern China. One forest was
      an old growth broad-leaved Korean pine (Pinus koraiensis) mixed forest; the other
      was a secondary poplar-birch forest. Growth of the two species and survival of C.
      mandshurica increased with stem number in the old growth forest, but not the
      secondary forest, suggesting the benefits of a multi-stemmed growth form are
      facultative. C. mandshurica also suffered more from overstory neighbor
      competition in the old growth forest, which may suggest that this species is less
      shade-tolerant than A. barbinerve. Moreover, the performance of the two species
      were clearly influenced by understory neighbors and soil variables in the old
      growth forest relative to the secondary forest, which may be due to different
      forest structure. We conclude that multiple stems are not always important for
      the persistence of shrub species. Even within the same species, the multi-stemmed
      benefits might be facultative, differing among forests and neighborhood
      compositions. 

PMID- 24887514
TI  - High-power biofuel cell textiles from woven biscrolled carbon nanotube yarns.
AB  - Biofuel cells that generate electricity from glucose in blood are promising for
      powering implantable biomedical devices. Immobilizing interconnected enzyme and
      redox mediator in a highly conducting, porous electrode maximizes their
      interaction with the electrolyte and minimizes diffusion distances for fuel and
      oxidant, thereby enhancing power density. Here we report that our separator-free
      carbon nanotube yarn biofuel cells provide an open-circuit voltage of 0.70 V, and
      a maximum areal power density of 2.18 mW cm(-2) that is three times higher than
      for previous carbon nanotube yarn biofuel cells. Biofuel cell operation in human
      serum provides high areal power output, as well as markedly increased lifetime
      (83% remained after 24 h), compared with previous unprotected biofuel cells. Our
      biscrolled yarn biofuel cells are woven into textiles having the mechanical
      robustness needed for implantation for glucose energy harvesting. 

PMID- 24887518
TI  - Big data-hype and promise.

PMID- 24887517
TI  - miR-21 overexpression enhances TGF-beta1-induced epithelial-to-mesenchymal
      transition by target smad7 and aggravates renal damage in diabetic nephropathy.
AB  - Epithelial-to-mesenchymal transition (EMT) plays an important role in renal
      interstitial fibrosis (RIF) with diabetic nephropathy (DN). Smad7 (a inhibitory
      smad), a downstream signaling molecules of TGF-beta1, represses the EMT. The
      physiological function of miR-21 is closely linked to EMT and RIF. However, it
      remained unclear whether miR-21 over-expression affected TGF-beta1-induced EMT by
      regulating smad7 in DN. In this study, real-time RT-PCR, cell transfection,
      luciferase reporter gene assays, western blot and confocal microscope were used,
      respectively. Here, we found that miR-21 expression was upregulated by TGF-beta1
      in time- and concentration -dependent manner. Moreover, miR-21 over-expression
      enhanced TGF-beta1-induced EMT(upregulation of a-SMA and downregulation of E
      cadherin) by directly down-regulating smad7/p-smad7 and indirectly up-regulating
      smad3/p-smad3, accompanied by the decrease of Ccr and the increase of col-IV, FN,
      the content of collagen fibers, RTBM, RTIAW and ACR. Meantime, the siRNA
      experiment showed that smad7 can directly regulate a-SMA and E-cadherin
      expression. More importantly, miR-21 inhibitor can not only inhibit EMT and
      fibrosis but also ameliorate renal structure and function. In conclusion, our
      results demonstrated that miR-21 overexpression can contribute to TGF-beta1
      induced EMT by inhibiting target smad7, and that targeting miR-21 may be a better
      alternative to directly suppress TGF-beta1-mediated fibrosis in DN. 

PMID- 24887516
TI  - Immortalization of human adipose-derived stromal cells: production of cell lines
      with high growth rate, mesenchymal marker expression and capability to secrete
      high levels of angiogenic factors.
AB  - INTRODUCTION: Human adipose-derived stromal cells (hASCs), due to their relative
      feasibility of isolation and ability to secrete large amounts of angiogenic
      factors, are being evaluated for regenerative medicine. However, their limited
      culture life span may represent an obstacle for both preclinical investigation
      and therapeutic use. To overcome this problem, hASCs immortalization was
      performed in order to obtain cells with in vitro prolonged life span but still
      maintain their mesenchymal marker expression and ability to secrete angiogenic
      factors. METHODS: hASCs were transduced with the human telomerase reverse
      transcriptase (hTERT) gene alone or in combination with either SV-40 or HPV E6/E7
      genes. Mesenchymal marker expression on immortalized hASCs lines was confirmed by
      flow cytometry (FC), differentiation potential was evaluated by
      immunocytochemistry and ELISA kits were used for evaluation of angiogenic
      factors. Green fluorescent protein (GFP) gene transduction was used to obtain
      fluorescent cells. RESULTS: We found that hTERT alone failed to immortalize hASCs
      (hASCs-T), while hTERT/SV40 (hASCs-TS) or hTERT/HPV E6/E7 (hASCs-TE) co
      transductions successfully immortalized cells. Both hASCs-TS and hASCs-TE were
      cultured for up to one year with a population doubling level (PDL) up to 100.
      Comparative studies between parental not transduced (hASCs-M) and immortalized
      cell lines showed that both hASCs-TS and hASCs-TE maintained a mesenchymal
      phenotypic profile, whereas differentiation properties were reduced particularly
      in hASCs-TS. Interestingly, hASCs-TS and hASCs-TE showed a capability to secrete
      significant amount of HGF and VEGF. Furthermore, hASCs-TS and hASCs-TE did not
      show tumorigenic properties in vitro although some chromosomal aberrations were
      detected. Finally, hASCs-TS and hASCs-TE lines were stably fluorescent upon
      transduction with the GFP gene. CONCLUSIONS: Here we demonstrated, for the first
      time, that hASCs, upon immortalization, maintain a strong capacity to secrete
      potent angiogenic molecules. By combining hASCs immortalization and their
      paracrine characteristics, we have developed a "hybridoma-like model" of hASCs
      that could have potential applications for discovering and producing molecules to
      use in regenerative medicine (process scale-up).

PMID- 24887519
TI  - Big data-what is it and what use is it?

PMID- 24887521
TI  - Big data and the electronic health record.
AB  - The electronic medical record has evolved from a digital representation of
      individual patient results and documents to information of large scale and
      complexity. Big Data refers to new technologies providing management and
      processing capabilities, targeting massive and disparate data sets. For an
      individual patient, techniques such as Natural Language Processing allow the
      integration and analysis of textual reports with structured results. For groups
      of patients, Big Data offers the promise of large-scale analysis of outcomes,
      patterns, temporal trends, and correlations. The evolution of Big Data analytics
      moves us from description and reporting to forecasting, predictive modeling, and
      decision optimization. 

PMID- 24887520
TI  - Leveraging data to systematically improve care: coronary artery disease
      management at Geisinger.
AB  - Coronary artery disease is complex chronic disease best managed by a team
      empowered by actionable data and a comprehensive approach, the ability to improve
      intermediate outcomes was dramatically enhanced after Geisinger created a system
      of care to do so. Continuous measurement of critical data elements of process and
      intermediate outcome measures allows the delivery of actionable information to
      the most appropriate team member, including the patients and family as team
      members. Continuous monitoring of the overall program looking for trends and
      opportunities across sites and regions allows for program enhancements. The
      comprehensive "all-or-none" bundled approach to care, which has already realized
      a 300% improvement, will be further enhanced by incorporating additional "Big
      Data" flows. 

PMID- 24887523
TI  - Self-care: the new principal care.
AB  - We predict self-care will become the new principal source of care. People living
      with diverse chronic conditions spend more time on self-management than with
      their providers. The increasing burden of chronic disease and costs coupled with
      value-based payments and innovative care models will generate a shift away from
      expensive specialized care toward high-value self-care facilitated by information
      technology, social support, and clinical expertise. This predicted shift in the
      value stream carries with it risks and uncertainties but will likely prevail as
      society seeks to confer "agency" by enabling people to make decisions and engage
      effectively in care coproduction. 

PMID- 24887522
TI  - Secure e-mailing between physicians and patients: transformational change in
      ambulatory care.
AB  - Secure e-mailing between Kaiser Permanente physicians and patients is widespread;
      primary care providers receive an average of 5 e-mails from patients each
      workday. However, on average, secure e-mailing with patients has not
      substantially impacted primary care provider workloads. Secure e-mail has been
      associated with increased member retention and improved quality of care. Separate
      studies associated patient portal and secure e-mail use with both decreased and
      increased use of other health care services, such as office visits, telephone
      encounters, emergency department visits, and hospitalizations. Directions for
      future research include more granular analysis of associations between patient
      physician secure e-mail and health care utilization. 

PMID- 24887524
TI  - The medication minefield: using computerized decision support systems to reduce
      preventable adverse drug events and hospitalizations.
AB  - Preventable adverse drug events (ADEs) are a source of avoidable
      hospitalizations, morbidity and mortality, especially among those older than 65
      years. Computerized decision support systems (CDSSs) can identify and address
      ADEs, but relatively little has been written about the effectiveness of such
      system in the community setting. This article will review some important studies
      on the causes of medication-related admissions in the ambulatory setting, where a
      lack of communication among prescribers creates a virtual minefield of medication
      risk. Some preliminary data will show how the application of CDSSs can affect the
      outcomes of care, including a reduction in preventable admissions and
      readmissions. 

PMID- 24887525
TI  - Critical reflections on the role of CBPR within an RCT community health worker
      prevention intervention.
AB  - Coalescence of culturally relevant and community-based research with traditional
      scientific inquiry is necessary for the translation of science into practice. One
      methodology that has been identified as an important missing link in achieving
      the goal of combining science and community practice is the community-based
      participatory research approach, or CBPR. To demonstrate how CBPR has been
      successfully blended with randomized control trial (RCT) methodology, we showcase
      a randomized community trial that has shown efficacy in reducing cardiovascular
      risk factors integrating community health workers. The purpose of this article is
      2-fold. First, it describes the process of merging the CBPR approach within an
      RCT framework and, second, it describes lessons learned in conducting CBPR-RCT
      research initiatives. 

PMID- 24887526
TI  - Identifying key patient demographics and organizational factors that contribute
      to health center participation in research.
AB  - Federally Qualified Health Centers are well positioned for translational research
      given their diverse patient population, unique characteristics, and community
      knowledge. This was the first national survey that assessed their research
      activities. Those with research experience were more likely to be urban and
      Health Care for the Homeless grantees and had more patients, minority patients,
      and physicians relative to nonphysician providers, enabling services providers,
      Medicaid revenues per Medicaid patient, and total revenues per patient than
      health centers with no experience and no future interest in research. Only
      enabling services providers to patient ratios and total patients remained
      significant after controlling for other factors. 

PMID- 24887527
TI  - The role of community health centers in assessing the social determinants of
      health for planning and policy: the example of frontier New Mexico.
AB  - This article examines the experience of a frontier-based community health center
      when it utilized the Tool for Health and Resilience in Vulnerable Environments
      (THRIVE) for assessing social determinants of health with a local health
      consortium. Community members (N = 357) rated safety, jobs, housing, and
      education among the top health issues. Community leaders integrated these health
      priorities in a countywide strategic planning process. This example of a frontier
      county in New Mexico demonstrates the critical role that community health centers
      play when engaging with local residents to assess community health needs for
      strategic planning and policy development. 

PMID- 24887528
TI  - Conceptual errors in the CMS refusal to make socioeconomic adjustments in
      readmission and other quality measures.
AB  - The Centers for Medicaid & Medicare Services has made a policy decision that
      socioeconomic factors should not be adjusted for in its various quality measures
      and point both to arguments made by the National Quality Forum and to analysis of
      the distributions of quality results to support this view. We present
      counterarguments to this viewpoint and use the results reported by the Centers
      for Medicaid & Medicare Services to support its position to demonstrate that
      adjustments are necessary. We further argue that the incentives for providers to
      improve performance would not be weakened by including socioeconomic factor
      adjustments. 

PMID- 24887529
TI  - Regular exercise is strongly associated with anticipated success for reducing
      health risks.
AB  - Regular exercise is a healthy behavior associated with desirable benefits.
      Regular exercise also makes manifest 2 fundamental behaviors-a choice and the
      discipline to continuously act on that choice. This cross-sectional analysis of
      more than 10 000 adults examines the association of regular exercise with
      unhealthy behaviors. Compared with people who are more regularly exercising,
      nonexercisers are less likely to choose to change an unhealthy habit.
      Nonexercisers are also much less likely to be confident of their success when
      they do choose a habit to change. Regular exercise seems to be a gateway behavior
      for reducing other unhealthy habits. 

PMID- 24887531
TI  - An easy route to synthetic analogues of radicamine B, codonopsine and
      codonopsinine from D-mannitol.
AB  - A general strategy for the synthesis of analogues of radicamine B has been
      carried out from D-mannitol. This method has been further extended to the
      synthesis of analogues of codonopsine and codonopsinine using appropriate
      Grignard reagents. The hence obtained molecules have been tested against various
      commercially available glycosidases and found to act as moderate to good
      inhibitors.

PMID- 24887532
TI  - Palliative radiation therapy in patients with metastasized pancreatic cancer -
      description of a rare patient group.
AB  - BACKGROUND: Pancreatic cancer (PAC) patients experience a high rate of
      locoregional recurrences and distant metastasis finally leading to their demise
      even after curatively-intended multidisciplinary treatment approaches including
      surgery, chemotherapy and radiotherapy. However, clinical reports on bone and
      brain metastases in PAC patients are extremely rare and thus timing and dose
      description are not well defined. Our work therefore summarizes a mono
      institutional experience on the use of radiotherapy (RT) for PAC patients with
      metastatic disease with the aim of identifying overall survival and treatment
      response in this rarely reported patient group. METHOD: Forty-four PAC patients
      with 66 metastatic lesions were treated with palliative radiotherapy (RT). Thirty
      three patients (48 lesions), 7 patients (11 lesions) and 5 patients (7 lesions)
      with bone, liver and brain metastases analyzed respectively were analyzed; one
      patient had both bone and cerebral metastases and was treated for the lesions,
      thus including him in both subgroups. Indications for RT were pain, neurological
      impairment, risk of pathological fracture or imminent danger for development of
      any of these conditions in case of tumor progression. Median age was 64 years
      (range 38 to 78 years) and there were 27 male (61%) and 17 (39%) female patients.
      Analyses of overall survival (OS) and local control were performed. OS was
      calculated from the first day of RT. RESULTS: Median overall survival (mOS) of
      all patients after start of RT was 4.2 months. Survival rates after 1, 3 and 6
      months were 79.3%, 55.3% and 30.3% respectively. Patients presenting with bone
      metastasis had a mOS of 3.1 months and after 1, 3 and 6 months, survival rates
      were 75.3%, 46.5% and 19.9% respectively. Symptomatic response to therapy was
      recorded in 85% of all evaluated patients with bone metastasis. Patients
      undergoing radiosurgery because of liver metastasis were locally controlled in
      all but one patient after a median follow-up of 8.3 months. CONCLUSION: Overall
      survival of all patients with metastatic disease was considerably worse. A major
      goal for the future must be the selection of an appropriate RT treatment in terms
      of duration and technique for these PAC patients.

PMID- 24887533
TI  - The impact of telemedicine in the postoperative care of the neurosurgery patient
      in an outpatient clinic: a unique perspective of this valuable resource in the
      developing world--an experience of more than 3000 teleconsultations.
AB  - Telemedicine has always been used as a teleconsultation tool in neurological
      emergencies (e.g., triage in head injuries, stroke, and cerebrovascular
      accidents). At Sri Sathya Sai Institute of Higher Medical Sciences, Bangalore,
      India, we have been operating two teleconsultation sessions per week for the
      postoperative patient population, addressing routine follow-up and semiemergent
      conditions in this cohort of patients. At our center more than 80% of the
      neurosurgical procedures are conducted in patients traveling more than 1500 km.
      Telemedicine as a routine tool in clinical medicine has significant financial and
      psychosocial benefits versus routine outpatient clinics. There are very few
      reports of telemedicine use in routine outpatient teleconsultations in the
      available neurosurgical literature; those that are present do not differentiate
      or analyze the use in routine versus emergency neurosurgery. We discuss the role
      of this underused resource in the developing countries and retrospectively
      analyze the clinical data in more than 1500 patients and 3000 teleconsultations
      during a period of 6 years. We address the financial implications, psychosocial
      factors, and several other factors that could make this relatively modest
      technology an indispensible tool in current neurosurgical practice, especially in
      a developing country like India. 

PMID- 24887534
TI  - Effectiveness of home exercise on pain, function, and strength of manual
      wheelchair users with spinal cord injury: a high-dose shoulder program with
      telerehabilitation.
AB  - OBJECTIVE: To test the effectiveness of a high-dose home
      exercise/telerehabilitation program for manual wheelchair users who have a spinal
      cord injury (SCI) by determining whether the intervention would reduce pain and
      increase function, as we hypothesized. DESIGN: A pre-post trial with outcomes
      measured at 3 time points: baseline, postintervention (12wk), and follow-up (>24
      wk). SETTING: Subjects performed an exercise program at their homes using
      telerehabilitation for therapist monitoring of technique and exercise
      advancement. Baseline and postintervention data were collected at a motion
      analysis laboratory in a tertiary medical center. PARTICIPANTS: A convenience
      sample of manual wheelchair users (N=16, 3 women; average age, 41y; average time
      in a wheelchair, 16y) with shoulder pain (average pain duration, 9y) and
      mechanical impingement signs on physical examination. INTERVENTIONS: A 12-week
      home exercise program of rotator cuff and scapular stabilization exercises was
      given to each participant. The program included a high dose of 3 sets of 30
      repetitions, 3 times weekly, and regular physical therapist supervision via
      videoconferencing. MAIN OUTCOME MEASURES: Primary outcomes of pain and function
      were measured with the Wheelchair User's Shoulder Pain Index (WUSPI),
      Disabilities of Arm, Shoulder, and Hand (DASH) Index, and Shoulder Rating
      Questionnaire (SRQ). Secondary outcomes of strength were measured with isometric
      strength tests of scapulothoracic and glenohumeral muscles, and a static fatigue
      test of the lower trapezius. RESULTS: Pain was reduced and function improved
      after the intervention. There was a significant main effect for pain and function
      between the 3 time points based on the Friedman signed-ranked test, WUSPI
      (chi(2)2=5.10, P=.014), DASH Index (chi(2)2=5.41, P=.012), and SRQ
      (chi(2)2=23.71, P<=.001). Wilcoxon signed-rank tests demonstrated that isometric
      strength measurements of the serratus anterior and scapular retractors increased
      after the exercise intervention ([t=2.42, P=.04] and [t=4.67, P=.003],
      respectively). Muscle impulse produced by the lower trapezius during a fatigue
      task also improved (t=2.2, P=.02). No differences were measured in isometric
      strength for the lower trapezius, glenohumeral rotators, and abductors between
      the baseline and 12-week time points. CONCLUSIONS: A high-dose scapular
      stabilizer and rotator cuff strengthening program using telerehabilitation for
      supervision holds promise for shoulder pain treatment in manual wheelchair users
      with SCI. Additional work is needed to determine the effectiveness compared with
      other interventions, as well as the potential for earlier intervention to prevent
      development of shoulder pain.

PMID- 24887536
TI  - Scanning electron microscopy comparison of the cleaning efficacy of a root canal
      system by Nd:YAG laser and rotary instruments.
AB  - This study evaluated the cleaning efficacy of a root canal system by Nd:YAG laser
      and rotary instruments. Sixty single-rooted human teeth were divided into four
      experimental groups (n=15). In the first group the teeth were prepared with a
      step-back technique using conventional K-files. In the second and third groups,
      tooth preparation was carried out using Nd:YAG laser and rotary NiTi instruments,
      respectively. Teeth in the fourth group were prepared by combined laser and
      rotary methods. The smear layer remaining on canal walls was then assessed by
      scanning electron microscopy in the coronal, middle, and apical portions. The
      comparison of smear layer removal efficacy between groups was carried out by
      Kruskal-Wallis and Mann-Whitney U tests. The mean grades of smear layer removal
      in rotary-laser, rotary, laser and step-back techniques were 1.34 +/- 0.18, 2.2
      +/- 0.28, 1.91 +/- 0.25, and 2.42 +/- 0.19, respectively. On the whole,
      differences between rotary-laser and rotary groups, step-back, and the three
      other techniques (rotary, laser, and rotary-laser) were significant at p=0.034.
      Based on the findings of this study, the cleaning efficacy of rotary, laser, and
      rotary-laser techniques were better than the step-back technique and the combined
      laser and rotary technique was the most efficient method.

PMID- 24887515
TI  - Genetic variation at CYP3A is associated with age at menarche and breast cancer
      risk: a case-control study.
AB  - INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism
      (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a
      reduction in premenopausal urinary estrone glucuronide levels and a modest
      reduction in risk of breast cancer in women age <=50 years. METHODS: We further
      investigated the association of rs10235235 with breast cancer risk in a large
      case control study of 47,346 cases and 47,570 controls from 52 studies
      participating in the Breast Cancer Association Consortium. Genotyping of
      rs10235235 was conducted using a custom Illumina Infinium array. Stratified
      analyses were conducted to determine whether this association was modified by age
      at diagnosis, ethnicity, age at menarche or tumor characteristics. RESULTS: We
      confirmed the association of rs10235235 with breast cancer risk for women of
      European ancestry but found no evidence that this association differed with age
      at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95%
      CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004),
      respectively (P(trend) = 0.02). There was no evidence of effect modification by
      tumor characteristics. rs10235235 was, however, associated with age at menarche
      in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the
      association between rs10235235 and breast cancer risk differed according to age
      at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a
      reduction in breast cancer risk for women who had their menarche age >=15 years
      (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) =
      0.002) but not for those who had their menarche age <=11 years (OR(het) = 1.06,
      95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29).
      CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide
      polymorphism to be associated with both breast cancer risk and age at menarche
      consistent with the well-documented association between later age at menarche and
      a reduction in breast cancer risk. These associations are likely mediated via an
      effect on circulating hormone levels.

PMID- 24887535
TI  - Maternal and paternal infant representations: a comparison between parents of
      term and preterm infants.
AB  - OBJECTIVE: Research on parental attachment representations after preterm birth is
      limited and inconclusive. The present study is the first in which maternal and
      paternal attachment representations after term, moderately and very preterm birth
      are compared. In addition, special attention was directed toward disrupted
      attachment representations. METHOD: Mothers and fathers of term infants (>= 37
      weeks of gestational age, n=71), moderately preterm infants (>= 32-37 weeks of
      gestational age, n=62) and very preterm infants (<32 weeks of gestational age,
      n=56) participated in the present study. Attachment representations (balanced,
      disengaged, distorted) about their infants were evaluated with the Working Model
      of the Child Interview (WMCI). To asses disrupted representations the coding of
      the WMCI was extended with the disrupted scale (WMCI-D). RESULTS: The three main
      classifications of attachment representations were not affected by preterm birth.
      In addition, there were no gender differences in the rate of balanced
      representations. In case of non-balanced representations however, maternal
      representations were more often distorted, whereas fathers showed more often
      disengaged representations. Results further revealed that maternal disrupted
      attachment representations were marked by role/boundary confusion or
      disorientation, whereas paternal disrupted attachment representations were
      characterized by withdrawal. CONCLUSION: Given the gender differences it is
      essential to tailor interventions according to the attachment representations of
      the parent, in order to be able to alter their non-balanced and/or disrupted
      attachment representations.

PMID- 24887537
TI  - Predicting outcomes after blunt chest wall trauma: development and external
      validation of a new prognostic model.
AB  - INTRODUCTION: Blunt chest wall trauma accounts for over 15% of all trauma
      admissions to Emergency Departments worldwide. Reported mortality rates vary
      between 4 and 60%. Management of this patient group is challenging as a result of
      the delayed on-set of complications. The aim of this study was to develop and
      validate a prognostic model that can be used to assist in the management of blunt
      chest wall trauma. METHODS: There were two distinct phases to the overall study;
      the development and the validation phases. In the first study phase, the
      prognostic model was developed through the retrospective analysis of all blunt
      chest wall trauma patients (n = 274) presenting to the Emergency Department of a
      regional trauma centre in Wales (2009 to 2011). Multivariable logistic regression
      was used to develop the model and identify the significant predictors for the
      development of complications. The model's accuracy and predictive capabilities
      were assessed. In the second study phase, external validation of the model was
      completed in a multi-centre prospective study (n = 237) in 2012. The model's
      accuracy and predictive capabilities were re-assessed for the validation sample.
      A risk score was developed for use in the clinical setting. RESULTS: Significant
      predictors of the development of complications were age, number of rib fractures,
      chronic lung disease, use of pre-injury anticoagulants and oxygen saturation
      levels. The final model demonstrated an excellent c-index of 0.96 (95% confidence
      intervals: 0.93 to 0.98). CONCLUSIONS: In our two phase study, we have developed
      and validated a prognostic model that can be used to assist in the management of
      blunt chest wall trauma patients. The final risk score provides the clinician
      with the probability of the development of complications for each individual
      patient.

PMID- 24887538
TI  - Endoscopic resection with hyaluronate solution for gastrointestinal lesions:
      systematic review and meta-analysis.
AB  - BACKGROUND: A wide range of outcomes are seen in the literature on the use of
      hyaluronate solution (HS) in endoscopic resection. However, there is little
      consensus on whether or not HS are beneficial for patients. The purpose of this
      meta-analysis was to evaluate the usefulness and safety of HS as submucosal fluid
      cushion for endoscopic resection in patients with gastrointestinal lesions.
      METHODS: We searched Pub Med, the Cochrane Library, EMBASE, Science Citation
      Index Expanded, CMB, VIP, and CNKI for the terms "endoscopic resection" and
      "hyaluronate solution" used in combination with the medical subject headings.
      Randomized controlled trials were considered. Meta-analysis was performed by
      RevMan 5.0 software. RESULTS: Four randomized control clinical trials (585
      patients) were included into the review analyses. There was no significant
      difference on en bloc resection and complete resection between the 2 groups. The
      fixed-effect meta-analyses did not favor the use of HS in preventing perforation,
      hemorrhage, and abdominal pain. The HS is more effective for maintenance of
      mucosal elevation than saline solution. CONCLUSIONS: Submucosal injection of HS
      could not increase the usefulness of en bloc resection and complete resection or
      seemed not to reduce perforation, hemorrhage, and abdominal pain compared with
      the saline solution. But, we were able to get benefit from maintenance of mucosal
      elevation.

PMID- 24887539
TI  - Systematic review and meta-analysis of transaxillary robotic thyroidectomy versus
      open thyroidectomy.
AB  - PURPOSE: It remains controversial whether the transaxillary robotic thyroidectomy
      (RT) is a feasible or better alternative to open thyroidectomy (OT) in thyroid
      surgery. We aimed to evaluate the efficacy of RT by pooling comparative studies
      of RT and OT in a systematic review and meta-analysis. MATERIALS AND METHODS:
      Original articles comparing transaxillary RT and conventional OT for thyroid
      diseases, published in the English language from1990 until February 3, 2013 were
      systematically searched in PubMed, Embase, Medline, and the Cochrane Library. The
      outcomes analyzed were postoperative complications, number of retrieved lymph
      nodes, operative time, postoperative hospital stay, and cosmetic satisfaction.
      RESULTS: Nine studies that fulfilled the eligibility criteria were included in
      the meta-analysis, of a total of 1615 patients (510 RT and 1105 OT). Compared
      with OT, RT showed a similar incidence of complications, number of retrieved
      lymph nodes, and length of postoperative hospital stay. The cosmetic effect of RT
      was superior to OT. But the operative time of RT was significantly longer than
      OT. CONCLUSIONS: The available data suggest that the efficacy of RT is similar to
      OT in the treatment of thyroid diseases on the whole. RT has a better cosmetic
      effect than OT. But longer operative time is needed by RT.

PMID- 24887541
TI  - Cyanoacrylate surgical glue for mesh fixation in laparoscopic total
      extraperitoneal hernia repair.
AB  - In an attempt to find the ideal surgical technique for mesh fixation during
      laparoscopic total extraperitoneal inguinal hernia repair, we evaluate the use of
      a synthetic surgical glue (N-butyl-cyanoacrylate-Glubran 2) in an effort to
      reduce postoperative pain and the complications associated with the use of
      staples. We have prospectively evaluated 61 consecutive patients (73 hernias)
      with a minimum follow-up period of 18 months and an average of 29.7 months,
      without any significant complications present. The majority (59%) only required
      low dosages of painkillers during the first 24 hours after surgery and have not
      experienced any cases of chronic pain or recurring hernias in the time period
      described. On the basis of this initial experience, the use of the surgical glue
      used to repair inguinal hernias with the laparoscopic total extraperitoneal
      technique has been proved to be a simple and effective surgical method for mesh
      fixation. 

PMID- 24887540
TI  - A prospective comparative study of blended and pure coagulation current in
      endoscopic mucosal resection of large sessile colorectal polyps.
AB  - BACKGROUND: The aim of this study was to compare pure coagulation and blended
      current in the resection of large colorectal sessile polyps (SPs). PATIENTS AND
      METHODS: Between January 2009 and June 2012, 84 patients (45 men, 39 women;
      median age 66 y; range, 42 to 88 y) with large colorectal SPs (diameter >=2 cm)
      were randomized in 1:1 ratio to undergo treatment by the "lift and cut" piecemeal
      resection technique. A total of 43 blended current subjects (group A) were well
      matched to 41 pure coagulation current subjects (group B), with a median lesion
      size of 3.9 cm (group A, 3.7 vs. group B, 4.2 cm; P=0.316), respectively. The
      rate of complications, the factors that predict complications, and the recurrence
      of adenoma were analyzed. RESULTS: Complete macroscopic resection was achieved in
      39 patients (90.7%) of group A and in 36 patients (87.6%) of group B (P=0.735).
      Argon plasma coagulation at resection's margins was performed in 10 patients
      (23.2%) of group A and in 14 patients (34.1%) of group B (P=0.269). Eight
      patients (9.5%) [group A, n=3 patients (7.1%) vs. group B, n=5 patients (12%);
      P=0.756] developed immediate (4) or delayed (4) bleeding. Four patients with
      bleeding were under treatment with selective serotonin reuptake inhibitors. All
      bleedings were successfully treated conservatively or with endoclipping and
      heater probe application. Perforation occurred in 1 patient of each group and was
      managed by clips closure and antibiotics and right hemicolectomy, respectively.
      Postpolypectomy syndrome was observed in 2 patients (4.6%) of group A and 3
      patients (7.3%) of group B (P=0.834). In 3 patients, the histopathologic analysis
      of resected SPs revealed invasive carcinoma, and surgical resection was performed
      in 1 patient. Two patients refused operation. Among the patients who underwent
      follow-up surveillance colonoscopy, a total recurrence rate of 25.67% of adenomas
      with no difference was observed between the 2 groups [group A, n=8 patients
      (21.6%) vs. group B, n=11 patients (31.4%); P=0.345]. Recurrence of adenoma was
      observed in 12 patients (16.22%) without and in 7 patients (9.46%) with argon
      plasma coagulation treatment. CONCLUSIONS: No difference was found in the rate of
      complications between the 2 types of current used in the resection of large
      colorectal SPs. However, an influence of selective serotonin reuptake inhibitors
      on postpolypectomy bleeding was observed, which deserves further investigation.

PMID- 24887542
TI  - Laparoscopic cholecystectomy in the pediatric population: a single-center
      experience.
AB  - OBJECTIVE: We aimed to review our experience with laparoscopic cholecystectomy in
      the pediatric population to better understand the associated complications and
      outcomes. METHODS: We performed a retrospective chart review of children below 18
      years of age who underwent laparoscopic cholecystectomy at a single academic
      institution between the years 1990 and 2010. RESULTS: Of the 325 cases of
      cholecystectomy, 202 (62.2%) were performed laparoscopically. The primary
      indication for surgery was symptomatic cholelithiasis (45.5%, n=92). Preoperative
      endoscopic retrograde cholangiopancreatography (ERCP) was performed in 25 (12.4%)
      patients. Variations in anatomy and technical difficulties (eg, presence of
      adhesions) were observed in 45 (22.3%) patients. Intraoperative cholangiogram was
      performed in 20 (9.9%) patients and 16 (7.9%) underwent concomitant splenectomy.
      Only 8 (4%) of the cases were converted to an open approach because of lack of
      anatomic clarity. There were zero common bile duct injuries; however, spillage of
      bile was present in 12 (5.9%) patients. Postoperative complications including
      wound infection, retained stones, abdominal abscess, and biloma, were observed in
      9 patients (4.5%). The median operative time was 117.5 minutes. The median
      postoperative hospital stay was 1 day. Nineteen (9.4%) patients had recurrence of
      abdominal pain without associated pathology. Three patients (1.5%) required
      postoperative ERCP. The average follow-up period was 54 months. CONCLUSIONS:
      Laparoscopic cholecystectomy in the pediatric population results in short
      postoperative hospital stay and has low complication rates. In particular, zero
      bile duct injuries were noted.

PMID- 24887543
TI  - Reply to safety of Veress needle insertion in laparoscopic bariatric surgery.

PMID- 24887545
TI  - Robot-assisted laparoscopic partial caudate lobe resection for hepatocellular
      carcinoma in cirrhotic liver.
AB  - PURPOSE: To evaluate the technical feasibility and safety of robot-assisted
      laparoscopic partial caudate lobe resection using the robotic surgical system.
      MATERIALS AND METHODS: This is a report of the use of robot-assisted laparoscopic
      partial caudate lobe resection on 2 patients with hepatocellular carcinoma.
      RESULTS: Robot-assisted laparoscopic partial caudate lobe resection was completed
      successfully in these 2 patients. The operating time was 137 and 150 minutes,
      respectively. The blood loss was 137 and 150 mL, respectively. They were able to
      tolerate liquids on the second postoperative day. Both patients recovered from
      the operation. They were discharged 4 and 5 days after the operation,
      respectively. The resected margins of both specimens were tumor free (R0
      resections). CONCLUSIONS: Robot-assisted laparoscopic partial caudate lobe
      resection is a feasible and safe procedure. Our results demonstrate the
      advantages of robotic system on short-term outcomes and suggest the extended
      indication of minimally invasive hepatectomy even in the technically challenging
      anatomic area.

PMID- 24887544
TI  - Should splenic flexure be routinely mobilized during laparoscopic low anterior
      resection for rectal cancer?

PMID- 24887546
TI  - A new technique for performing endoscopic pyloromyotomy by gastric submucosal
      tunnel dissection.
AB  - AIM: To investigate the feasibility of a new endoscopic pyloromyotomy technique.
      MATERIALS AND METHODS: Endoscopic pyloromyotomy through a gastric submucosal
      tunnel was performed in 6 pigs. At the greater curvature, 2 cm proximal to the
      pylorus, we incised the mucosa and dissected the submucosal tunnel up to the
      pyloric ring. The pyloric muscular ring was sectioned, and then the gastric
      mucosal incision was closed with metallic clips. The pigs were then euthanized
      and necropsies were performed. RESULTS: Section of the pyloric ring was
      successful in all 6 pigs. Small perforations occurred in 2 of the pigs, and there
      was limited bleeding in 1 pig. Necropsy and histologic evaluation confirmed the
      pyloric section. CONCLUSIONS: This technique is feasible, easy to perform, and
      maybe alternative to pyloroplasty in selected cases. Experimental comparative
      studies with other techniques still must be performed.

PMID- 24887548
TI  - Equilibrium unfolding of cyclophilin from Leishmania donovani: characterization
      of intermediate states.
AB  - Cyclophilin from Leishmania donovani (LdCyp) is a ubiquitous peptidyl-prolyl cis
      trans isomerase involved in a host of important cellular activities, such as
      signaling, heat shock response, chaperone activity, mitochondrial pore
      maintenance and regulation of HIV-1 infectivity. It also acts as the prime
      cellular target for the auto-immune drug cyclosporine A (CsA). LdCyp is composed
      of a beta barrel encompassing the unique hydrophobic core of the molecule and is
      flanked by two helices (H1, H2) on either end of the barrel. The protein contains
      a lone partially exposed tryptophan. In the present work the equilibrium
      unfolding of LdCyp has been studied by fluorescence, circular dichroism and the
      non-coincidence of their respective Cm's, indicates a non-two state transition.
      This fact was further corroborated by binding studies of the protein with bis-ANS
      and the lack of an isochromatic point in far UV CD. The thermal stability of the
      possible intermediates was characterized by differential scanning calorimetry.
      Further, MD simulations performed at 310, 400 and 450K exhibited the tendency of
      both helices to partially unwind and adopt non-native geometries with respect to
      the core, quite early in the unfolding process, in contrast to the relatively
      stable beta barrel. 

PMID- 24887549
TI  - Hypoglycemic and hepatoprotective effects of polysaccharides from Artemisia
      sphaerocephala Krasch seeds.
AB  - Intake of dietary high fructose (HF) exerts a number of adverse metabolic
      effects. The present study was to investigate whether Artemisia sphaerocephala
      Krasch seed polysaccharides (ASKP) alleviated hyperglycemia, hepatic steatosis
      and oxidative injury in mice fed HF water. After 8 weeks of the experiment,
      administration of ASKP at 400 and 800mg/kgbw significantly reduced the fasting
      serum glucose, insulin concentrations and the homeostasis model assessment of
      basal insulin resistance (HOMA-IR) of the mice fed 20% HF water. In the oral
      glucose tolerance test, the administration of ASKP at 400 and 800mg/kgbw had a
      reduced plasma glucose concentrations after 15min of glucose loading in HF-fed
      mice, indicating that ASKP improved glucose intolerance. ASKP also remarkably
      ameliorated the HF-induced elevation of liver lipid contents and oxidative injury
      in mice, and caused the reduction of liver lipid peroxidation and the elevation
      of hepatic antioxidant system. Histopathology of the liver by conventional H&E
      and Oil Red O staining confirmed the liver steatosis and oxidative injury induced
      by HF diet and the hepatoprotective effect of ASKP. This is the first report
      showing that ASKP can ameliorate the high fructose-induced hyperglycemia, hepatic
      steatosis and oxidative injury. 

PMID- 24887550
TI  - Synthesis and characterization of modified starch/polybutadiene as novel
      transdermal drug delivery system.
AB  - Transdermal drug delivery systems are topically administered medicaments in the
      form of patches that deliver drugs for systemic effects at a predetermined and
      controlled rate. It works very simply in which drug is applied inside the patch
      and it is worn on skin for long period of time. Polymer matrix, drug, permeation
      enhancers are the main components of transdermal drug delivery systems. The
      objective of the present study was to develop the modified starch and 1,4-cis
      polybutadiene nanoparticles as novel polymer matrix system. We have been studied
      the properties of a novel transdermal drug delivery system with clonidine as drug
      model. 

PMID- 24887547
TI  - A shared transcriptional program in early breast neoplasias despite genetic and
      clinical distinctions.
AB  - BACKGROUND: The earliest recognizable stages of breast neoplasia are lesions that
      represent a heterogeneous collection of epithelial proliferations currently
      classified based on morphology. Their role in the development of breast cancer is
      not well understood but insight into the critical events at this early stage will
      improve efforts in breast cancer detection and prevention. These microscopic
      lesions are technically difficult to study so very little is known about their
      molecular alterations. RESULTS: To characterize the transcriptional changes of
      early breast neoplasia, we sequenced 3'- end enriched RNAseq libraries from
      formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched
      normal breast and carcinoma samples from 25 patients. We find that gene
      expression patterns within early neoplasias are distinct from both normal and
      breast cancer patterns and identify a pattern of pro-oncogenic changes, including
      elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We
      validate these findings on a second independent gene expression profile data set
      generated by whole transcriptome sequencing. Measurements of protein expression
      by immunohistochemistry on an independent set of early neoplasias confirms that
      ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently
      upregulated at this early stage. The early neoplasia samples also demonstrate
      coordinated changes in long non-coding RNA expression and microenvironment
      stromal gene expression patterns. CONCLUSIONS: This study is the first
      examination of global gene expression in early breast neoplasia, and the genes
      identified here represent candidate participants in the earliest molecular events
      in the development of breast cancer.

PMID- 24887552
TI  - Health and safety issues for travelers attending the World Cup and Summer Olympic
      and Paralympic Games in Brazil, 2014 to 2016.
AB  - IMPORTANCE: Travelers from around the globe will attend the 2014 Federation
      Internationale de Football Association (FIFA) World Cup and the 2016 Olympic and
      Paralympic Games in Brazil. Travelers to these mass gathering events may be
      exposed to a range of health risks, including a variety of infectious diseases.
      Most travelers who become ill will present to their primary care physicians, and
      thus it is important that clinicians are aware of the risks their patients
      encountered. OBJECTIVE: To highlight health and safety concerns for people
      traveling to these events in Brazil so that health care practitioners can better
      prepare travelers before they travel and more effectively diagnose and treat
      travelers after they return. EVIDENCE REVIEW: We reviewed both peer-reviewed and
      gray literature to identify health outcomes associated with travel to Brazil and
      mass gatherings. Thirteen specific infectious diseases are described in terms of
      signs, symptoms, and treatment. Relevant safety and security concerns are also
      discussed. FINDINGS: Travelers to Brazil for mass gathering events face unique
      health risks associated with their travel. CONCLUSIONS AND RELEVANCE: Travelers
      should consult a health care practitioner 4 to 6 weeks before travel to Brazil
      and seek up-to-date information regarding their specific itineraries. For the
      most up-to-date information, health care practitioners can visit the Centers for
      Disease Control and Prevention (CDC) Travelers' Health website
      (http://wwwnc.cdc.gov/travel) or review CDC's Yellow Book online
      (http://wwwnc.cdc.gov/travel/page/yellowbook-home-2014).

PMID- 24887551
TI  - Functional cartilage repair capacity of de-differentiated, chondrocyte- and
      mesenchymal stem cell-laden hydrogels in vitro.
AB  - OBJECTIVE: The long-term performance of cell-seeded matrix-based cartilage
      constructs depends on (1) the development of sufficient biomechanical properties,
      and (2) lateral integration with host tissues, both of which require cartilage
      specific matrix deposition within the scaffold. In this study, we have examined
      the potential of tissue-engineered cartilage analogs developed using different
      cell types, i.e., mesenchymal stem cells (MSCs) vs chondrocytes and de
      differentiated chondrocytes, in an established "construct in cartilage ring"
      model. DESIGN: Cell-laden constructs of differentiated chondrocytes, de
      differentiated chondrocytes after two, five or eight population doublings, and
      MSCs were either implanted into a native cartilage ring immediately after
      fabrication (immature group) or pre-treated for 21 days in a transforming growth
      factor-beta3 (TGF-beta3) containing medium prior to implantation. After
      additional culture for 28 days in a serum-free, chemically defined medium, the
      extent of lateral integration, and biochemical and biomechanical characteristics
      of the implants as hybrid constructs were assessed. RESULTS: The quality of
      integration, the amount of accumulated cartilage-specific matrix components and
      associated biomechanical properties were found to be highest when using
      differentiated chondrocytes. De-differentiation of chondrocytes negatively
      impacted the properties of the implants, as even two population doublings of the
      chondrocytes in culture significantly lowered cartilage repair capacity. In
      contrast, MSCs showed chondrogenic differentiation with TGF-beta3 pre-treatment
      and superior integrational behavior. CONCLUSIONS: Chondrocyte expansion and de
      differentiation impaired the cell response, resulting in inferior cartilage
      repair in vitro. With TGF-beta3 pre-treatment, MSCs were able to undergo
      sustained chondrogenic differentiation and exhibited superior matrix deposition
      and integration compared to de-differentiated chondrocytes.

PMID- 24887553
TI  - Printing three-dimensional tissue analogues with decellularized extracellular
      matrix bioink.
AB  - The ability to print and pattern all the components that make up a tissue (cells
      and matrix materials) in three dimensions to generate structures similar to
      tissues is an exciting prospect of bioprinting. However, the majority of the
      matrix materials used so far for bioprinting cannot represent the complexity of
      natural extracellular matrix (ECM) and thus are unable to reconstitute the
      intrinsic cellular morphologies and functions. Here, we develop a method for the
      bioprinting of cell-laden constructs with novel decellularized extracellular
      matrix (dECM) bioink capable of providing an optimized microenvironment conducive
      to the growth of three-dimensional structured tissue. We show the versatility and
      flexibility of the developed bioprinting process using tissue-specific dECM
      bioinks, including adipose, cartilage and heart tissues, capable of providing
      crucial cues for cells engraftment, survival and long-term function. We achieve
      high cell viability and functionality of the printed dECM structures using our
      bioprinting method. 

PMID- 24887554
TI  - Aldehyde dehydrogenase and estrogen receptor define a hierarchy of cellular
      differentiation in the normal human mammary epithelium.
AB  - INTRODUCTION: Although estrogen and progesterone play a key role in normal
      mammary development and in breast cancer, the potential for proliferation and
      lineage differentiation as well as origin of cells that express the estrogen
      receptor (ER) in normal breast epithelium are not known. Some evidence suggests
      that normal human mammary stem/progenitor cells are ER-, but the identity of
      these cells and the cellular hierarchy of breast epithelium are still subjects of
      controversy. It is likely that elucidation of these aspects will bring insight
      into the cellular origin of breast cancer subtypes. METHODS: We used fluorescence
      activated cell sorting of primary human mammary epithelial cells along with in
      vitro and in vivo functional assays to examine the hierarchic relation between
      cells with aldehyde dehydrogenase enzymatic activity (ALDH+ cells) and ER+ cells
      in the normal human breast epithelium. We assessed the proliferation and lineage
      differentiation potential of these cells in vitro and in vivo. A gene reporter
      assay was used to separate live ER+ and ER- mammary epithelial cells. With shRNA
      mediated knockdown, we investigated the role of ALDH isoforms in the
      functionality of mammary epithelial progenitor cells. RESULTS: We describe a
      cellular hierarchy in the normal human mammary gland in which ER-/ALDH+ cells
      with functional properties of stem/progenitor cells generate ER+ progenitor
      cells, which in turn give rise to cells of luminal lineage. We show that the
      ALDH1A1 isoform, through its function in the retinoic acid metabolism, affects
      the proliferation and/or early differentiation of stem/progenitor cells and is
      important for branching morphogenesis. CONCLUSIONS: This study presents direct
      evidence that ER+ cells are generated by ER-/ALDH+ stem/progenitor cells. We also
      show that ER+ cells are able to generate cell progeny of luminal lineage in vitro
      and in vivo. Loss of ALDH1A1 function impairs this process, as well as branching
      morphogenesis and clonogenicity in suspension culture. This latter effect is
      reversed by treatment with retinoic acid.

PMID- 24887555
TI  - Synergies for improving oil palm production and forest conservation in floodplain
      landscapes.
AB  - Lowland tropical forests are increasingly threatened with conversion to oil palm
      as global demand and high profit drives crop expansion throughout the world's
      tropical regions. Yet, landscapes are not homogeneous and regional constraints
      dictate land suitability for this crop. We conducted a regional study to
      investigate spatial and economic components of forest conversion to oil palm
      within a tropical floodplain in the Lower Kinabatangan, Sabah, Malaysian Borneo.
      The Kinabatangan ecosystem harbours significant biodiversity with globally
      threatened species but has suffered forest loss and fragmentation. We mapped the
      oil palm and forested landscapes (using object-based-image analysis,
      classification and regression tree analysis and on-screen digitising of high
      resolution imagery) and undertook economic modelling. Within the study region
      (520,269 ha), 250,617 ha is cultivated with oil palm with 77% having high Net
      Present-Value (NPV) estimates ($413/ha-yr-$637/ha-yr); but 20.5% is under
      producing. In fact 6.3% (15,810 ha) of oil palm is commercially redundant (with
      negative NPV of $-299/ha-yr-$-65/ha-yr) due to palm mortality from flood
      inundation. These areas would have been important riparian or flooded forest
      types. Moreover, 30,173 ha of unprotected forest remain and despite its value for
      connectivity and biodiversity 64% is allocated for future oil palm. However, we
      estimate that at minimum 54% of these forests are unsuitable for this crop due to
      inundation events. If conversion to oil palm occurs, we predict a further 16,207
      ha will become commercially redundant. This means that over 32,000 ha of forest
      within the floodplain would have been converted for little or no financial gain
      yet with significant cost to the ecosystem. Our findings have globally relevant
      implications for similar floodplain landscapes undergoing forest transformation
      to agriculture such as oil palm. Understanding landscape level constraints to
      this crop, and transferring these into policy and practice, may provide
      conservation and economic opportunities within these seemingly high opportunity
      cost landscapes. 

PMID- 24887556
TI  - Stilbene induced inhibition of androgen receptor dimerization: implications for
      AR and ARDeltaLBD-signalling in human prostate cancer cells.
AB  - BACKGROUND: Advanced castration resistant prostate cancer (CRPC) is often
      characterized by an increase of C-terminally truncated, constitutively active
      androgen receptor (AR) variants. Due to the absence of a ligand binding domain
      located in the AR-C-terminus, these receptor variants (also termed ARDeltaLBD)
      are unable to respond to all classical forms of endocrine treatments like
      surgical/chemical castration and/or application of anti-androgens. METHODOLOGY:
      In this study we tested the effects of the naturally occurring stilbene
      resveratrol (RSV) and (E)-4-(2, 6-Difluorostyryl)-N, N-dimethylaniline, a
      fluorinated dialkylaminostilbene (FIDAS) on AR- and ARDeltaLBD in prostate cancer
      cells. The ability of the compounds to modulate transcriptional activity of AR
      and the ARDeltaLBD-variant Q640X was shown by reporter gene assays. Expression of
      endogenous AR and ARDeltaLBD mRNA and protein levels were determined by qRT-PCR
      and Western Blot. Nuclear translocation of AR-molecules was analyzed by
      fluorescence microscopy. AR and ARDeltaLBD/Q640X homo-/heterodimer formation was
      assessed by mammalian two hybrid assays. Biological activity of both compounds in
      vivo was demonstrated using a chick chorioallantoic membrane xenograft assay.
      RESULTS: The stilbenes RSV and FIDAS were able to significantly diminish AR and
      Q640X-signalling. Successful inhibition of the Q640X suggests that RSV and FIDAS
      are not interfering with the AR-ligand binding domain like all currently
      available anti-hormonal drugs. Repression of AR and Q640X-signalling by RSV and
      FIDAS in prostate cancer cells was caused by an inhibition of the AR and/or Q640X
      dimerization. Although systemic bioavailability of both stilbenes is very low,
      both compounds were also able to downregulate tumor growth and AR-signalling in
      vivo. CONCLUSION: RSV and FIDAS are able to inhibit the dimerization of AR and
      ARDeltaLBD molecules suggesting that stilbenes might serve as lead compounds for
      a novel generation of AR-inhibitors.

PMID- 24887557
TI  - Antimicrobial and anti-inflammatory activities of endophytic fungi Talaromyces
      wortmannii extracts against acne-inducing bacteria.
AB  - Acne vulgaris is the most common skin disease, causing significant psychosocial
      problems such as anxiety and depression similar to a chronic illness for those
      afflicted. Currently, obtainable agents for acne treatment have limited use.
      Thus, development of novel agents to treat this disease is a high medical need.
      The anaerobic bacterium Propionibacterium acnes has been implicated in the
      inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such
      as the interleukin-8 (IL-8) via the NF-kappaB and MAPK pathways. Talaromyces
      wortmannii is an endophytic fungus, which is known to produce high bioactive
      natural compounds. We hypothesize that compound C but also the crude extract from
      T. wortmannii may possess both antibacterial activity especially against P. acnes
      and also anti-inflammatory properties by inhibiting TNF-alpha-induced ICAM-1
      expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT)
      with P. acnes significantly increased NF-kappaB and activator protein-1 (AP-1)
      activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated
      activation of NF-kappaB and AP-1 by inhibiting IkappaB degradation and the
      phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent
      manner. Based on these results, compound C has effective antimicrobial activity
      against P. acnes and anti-inflammatory activity, and we suggest that this
      substance or the crude extract are alternative treatments for antibiotic/anti
      inflammatory therapy for acne vulgaris. 

PMID- 24887558
TI  - A reduction in Npas4 expression results in delayed neural differentiation of
      mouse embryonic stem cells.
AB  - INTRODUCTION: Npas4 is a calcium-dependent transcription factor expressed within
      neurons of the brain where it regulates the expression of several genes that are
      important for neuronal survival and synaptic plasticity. It is known that in the
      adult brain Npas4 plays an important role in several key aspects of neurobiology
      including inhibitory synapse formation, neuroprotection and memory, yet very
      little is known about the role of Npas4 during neurodevelopment. The aim of this
      study was to examine the expression and function of Npas4 during nervous system
      development by using a combination of in vivo experiments in the developing mouse
      embryo and neural differentiation of embryonic stem cells (ESCs) as an in vitro
      model of the early stages of embryogenesis. METHODS: Two different neural
      differentiation paradigms were used to investigate Npas4 expression during
      neurodevelopment in vitro; adherent monolayer differentiation of mouse ESCs in
      N2B27 medium and Noggin-induced differentiation of human ESCs. This work was
      complemented by direct analysis of Npas4 expression in the mouse embryo. The
      function of Npas4 in the context of neurodevelopment was investigated using loss
      of-function experiments in vitro. We created several mouse ESC lines in which
      Npas4 expression was reduced during neural differentiation through RNA
      interference and we then analyzed the ability of these Npas4 knockdown mouse ESCs
      lines to undergo neural differentiation. RESULTS: We found that while Npas4 is
      not expressed in undifferentiated ESCs, it becomes transiently up-regulated
      during neural differentiation of both mouse and human ESCs at a stage of
      differentiation that is characterized by proliferation of neural progenitor
      cells. This was corroborated by analysis of Npas4 expression in the mouse embryo
      where the Npas4 transcript was detected specifically in the developing forebrain
      beginning at embryonic day 9.5. Finally, knockdown of Npas4 expression in mouse
      ESCs undergoing neural differentiation affected their ability to differentiate
      appropriately, resulting in delayed neural differentiation. CONCLUSIONS: Here we
      provide the first evidence that Npas4 is expressed during embryonic development
      and that it may have a developmental role that is unrelated to its function in
      the adult brain.

PMID- 24887559
TI  - Selective ALK inhibitor alectinib with potent antitumor activity in models of
      crizotinib resistance.
AB  - The clinical efficacy of the ALK inhibitor crizotinib has been demonstrated in
      ALK fusion-positive NSCLC; however, resistance to crizotinib certainly occurs
      through ALK secondary mutations in clinical use. Here we examined the efficacy of
      a selective ALK inhibitor alectinib/CH5424802 in models of crizotinib resistance.
      Alectinib led to tumor size reduction in EML4-ALK-positive xenograft tumors that
      failed to regress fully during the treatment with crizotinib. In addition,
      alectinib inhibited the growth of some EML4-ALK mutant-driven tumors, including
      the G1269A model. These results demonstrated that alectinib might provide
      therapeutic opportunities for crizotinib-treated patients with ALK secondary
      mutations. 

PMID- 24887560
TI  - An novel inhibitor of TGF-beta type I receptor, IN-1130, blocks breast cancer
      lung metastasis through inhibition of epithelial-mesenchymal transition.
AB  - TGF-beta signaling plays an important role in breast cancer progression and
      metastasis. Epithelial-mesenchymal transition (EMT) is an important step in the
      progression of solid tumors to metastatic disease. We previously reported that IN
      1130, a novel transforming growth factor-beta type I receptor kinase (ALK5)
      inhibitor, suppressed renal fibrosis in obstructive nephropathy (Moon et al.,
      2006). Here, we show that IN-1130 suppressed EMT and the lung metastasis of
      mammary tumors in mouse models. Treating human and mouse cell lines with IN-1130
      inhibited TGF-beta-mediated transcriptional activation, the phosphorylation and
      nuclear translocation of Smad2, and TGF-beta-induced-EMT, which induces
      morphological changes in epithelial cells. Additionally, we demonstrated that IN
      1130 blocked TGF-beta-induced 4T1 mammary cancer cell migration and invasion. The
      TGF-beta-mediated increase in matrix metalloproteinase (MMP)-2 and MMP-9
      expression was restored by IN-1130 co-treatment with TGF-beta in human epithelial
      cells and in 4T1 cells. Furthermore, we found that lung metastasis from primary
      breast cancer was inhibited by IN-1130 in both 4T1-xenografted BALB/c mice and
      MMTV/c-Neu transgenic mice without any change in primary tumor volume. IN-1130
      prolonged the life span of tumor-bearing mice. In summary, this study indicated
      that IN-1130 has therapeutic potential for preventing breast cancer metastasis to
      the lung. 

PMID- 24887562
TI  - A mitochondria-targeted turn-on fluorescent probe based on a rhodol platform for
      the detection of copper(I).
AB  - A new spirocyclized rhodol-based fluorescent probe has been developed for
      detecting mitochondrial Cu(+). Alkylation of the hydroxy group of a xanthene
      moiety with a tris(2-pyridylmethyl)amine-based ligand induced the formation of a
      non-fluorescent spirocyclic structure. The reaction with Cu(+) in the presence of
      submillimolar concentrations of glutathione at physiological pH resulted in the
      elimination of the ligand together with an increase in the fluorescence of the
      rhodol fluorophore. This probe was used to visualize mitochondrial Cu(+) in
      copper supplemented cells. 

PMID- 24887561
TI  - A non-canonical NRPS is involved in the synthesis of fungisporin and related
      hydrophobic cyclic tetrapeptides in Penicillium chrysogenum.
AB  - The filamentous fungus Penicillium chrysogenum harbors an astonishing variety of
      nonribosomal peptide synthetase genes, which encode proteins known to produce
      complex bioactive metabolites from simple building blocks. Here we report a novel
      non-canonical tetra-modular nonribosomal peptide synthetase (NRPS) with
      microheterogenicity of all involved adenylation domains towards their respective
      substrates. By deleting the putative gene in combination with comparative
      metabolite profiling various unique cyclic and derived linear tetrapeptides were
      identified which were associated with this NRPS, including fungisporin. In
      combination with substrate predictions for each module, we propose a mechanism
      for a 'trans-acting' adenylation domain. 

PMID- 24887563
TI  - Caesarean scar choriocarcinoma: a case report and review of the literature.
AB  - OBJECTIVE: To report the clinical characteristics, pathologic findings and
      treatments of a patient with a Caesarean scar choriocarcinoma. PATIENT HISTORY: A
      22-year-old woman had a diagnosis of primary gestational choriocarcinoma in a
      uterine Caesarean scar misdiagnosed as a normal Caesarean scar pregnancy. The
      patient underwent selective uterine artery embolization coupled with methotrexate
      arterial injection, along with dilatation and curettage of the uterine Caesarean
      scar. Finally, she received eight courses of multiagent chemotherapy. The
      reproductive function of the patient was preserved. CONCLUSIONS: Primary
      gestational choriocarcinoma out of the uterine corpus is a rare disease. A
      Caesarean scar choriocarcinoma is an extremely unusual example of this entity
      because of its unique position. To the best of our knowledge, this is the first
      report of this phenomenon. Our experience and a literature review suggest that a
      clinical diagnosis of a primary gestational choriocarcinoma of the uterine
      Caesarean scar is difficult to make, and uterine artery embolization is
      beneficial to prevent massive bleeding before curettage.

PMID- 24887565
TI  - N-type voltage-dependent Ca2+ channel in non-excitable microglial cells in mice
      is involved in the pathophysiology of neuropathic pain.
AB  - Peripheral nerve injury induces neuropathic pain which is characterized by
      tactile allodynia and thermal hyperalgesia. N-type voltage-dependent Ca(2+)
      channel (VDCC) plays pivotal roles in the development of neuropathic pain, since
      mice lacking Cav2.2, the pore-forming subunit of N-type VDCC, show greatly
      reduced symptoms of both tactile allodynia and thermal hyperalgesia. Our study on
      gene expression profiles of the Cav2.2 knockout (KO) spinal cord after spinal
      nerve ligation (SNL)-injury revealed altered expression of genes known to be
      expressed in microglia, raising an odd idea that N-type VDCC may function in not
      only excitable (neurons) but also non-excitable (microglia) cells in neuropathic
      pain state. In the present study, we have tested this idea by using a transgenic
      mouse line, in which suppression of Cav2.2 expression can be achieved
      specifically in microglia/macrophage by the application of tamoxifen. We found
      SNL-operated transgenic mice exhibited greatly reduced signs of tactile
      allodynia, whereas the degree of thermal hyperalgesia was almost the same as that
      of control. Immunohistochemical analysis of the transgenic lumbar spinal cord
      revealed reduced accumulation of Iba1-positive cells (microglia/macrophage)
      around the injured neurons, indicating microglial N-type VDCC is important for
      accumulation of microglia at the lesion sites. Although the mechanism of its
      activation is not clear at present, activation of N-type VDCC expressed in non
      excitable microglial cells contributes to the pathophysiology of neuropathic
      pain. 

PMID- 24887566
TI  - Mollugin induces tumor cell apoptosis and autophagy via the PI3K/AKT/mTOR/p70S6K
      and ERK signaling pathways.
AB  - Mollugin, a bioactive phytochemical isolated from Rubia cordifolia L., has shown
      preclinical anticancer efficacy in various cancer models. However the effects of
      mollugin in regulating cancer cell survival and death remains undefined. In the
      present study we found that mollugin exhibited cytotoxicity on various cancer
      models. The suppression of cell viability was due to the induction of
      mitochondria apoptosis. In addition, the presence of autophagic hallmarks was
      observed in mollugin-treated cells. Notably, blockade of autophagy by a chemical
      inhibitor or RNA interference enhanced the cytotoxicity of mollugin. Further
      experiments demonstrated that phosphatidylinositide 3-kinases/protein kinase
      B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) and
      extracellular regulated protein kinases (ERK) signaling pathways participated in
      mollugin-induced autophagy and apoptosis. Together, these findings support
      further studies of mollugin as candidate for treatment of human cancer cells. 

PMID- 24887567
TI  - Improved H2S gas sensing properties of ZnO nanorods decorated by a several nm ZnS
      thin layer.
AB  - To avoid a spontaneous reaction between ZnO gas sensing materials and detected
      H2S gas, ZnO nanorods decorated with a several nm ZnS thin layer were designed.
      The ZnS-decorated layer was prepared by passivating oriented ZnO nanorods in a
      H2S atmosphere. The effect of the passivation processes on the H2S sensing
      properties was investigated. It was found that ZnO nanorods decorated with a 2 nm
      thick ZnS layer possessed a repeatable and superior response to ppm-level H2S at
      room temperature. Moreover, a confinement effect was proposed to explain the
      improved sensing properties of the decorated ZnO nanorods. 

PMID- 24887568
TI  - Witnessing traumatic events causes severe behavioral impairments in rats.
AB  - Witnessing a traumatic event but not directly experiencing it can be
      psychologically quite damaging. In North America alone, ~30% of individuals who
      witness a traumatic event develop post-traumatic stress disorder (PTSD). While
      effects of direct trauma are evident, consequences of indirect or secondary
      trauma are often ignored. Also unclear is the role of social support in the
      consequences of these experiences. The social defeat paradigm, which involves
      aggressive encounters by a large Long-Evans male rat (resident) towards a smaller
      Sprague-Dawley male rat (intruder), is considered a rodent model of PTSD. We have
      modified this model to create a trauma witness model (TWM) and have used our TWM
      model to also evaluate social support effects. Basically, when an intruder rat is
      placed into the home cage of a resident rat, it encounters an agonistic behavior
      resulting in intruder subordination. The socially defeated intruder is designated
      the SD rat. A second rat, the cage mate of the SD, is positioned to witness the
      event and is the trauma witnessing (TW) rat. Experiments were performed in two
      different experimental conditions. In one, the SD and TW rats were cagemates and
      acclimatized together. Then, one SD rat was subjected to three sessions of social
      defeat for 7 d. TW rat witnessed these events. After each social defeat exposure,
      the TW and SD rats were housed together. In the second, the TW and SD rats were
      housed separately starting after the first defeat. At the end of each protocol,
      depression-anxiety-like behavior and memory tests were conducted on the SD and TW
      rats, blood withdrawn and specific organs collected. Witnessing traumatic events
      led to depression- and anxiety-like behavior and produced memory deficits in TW
      rats associated with elevated corticosterone levels. 

PMID- 24887570
TI  - Re: Regarding letter by MacGregor and Du concerning "Vanadium exposure-induced
      neurobehavioral alterations among Chinese workers".

PMID- 24887564
TI  - Intracellular pH in sperm physiology.
AB  - Intracellular pH (pHi) regulation is essential for cell function. Notably,
      several unique sperm ion transporters and enzymes whose elimination causes
      infertility are either pHi dependent or somehow related to pHi regulation.
      Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm
      specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear
      that pHi regulation is of the utmost importance for sperm physiology. This review
      briefly summarizes the key components involved in pHi regulation, their
      characteristics and participation in fundamental sperm functions such as
      motility, maturation and the acrosome reaction. 

PMID- 24887569
TI  - Does contemporary vancomycin dosing achieve therapeutic targets in a
      heterogeneous clinical cohort of critically ill patients? Data from the
      multinational DALI study.
AB  - INTRODUCTION: The objective of this study was to describe the pharmacokinetics of
      vancomycin in ICU patients and to examine whether contemporary antibiotic dosing
      results in concentrations that have been associated with favourable response.
      METHODS: The Defining Antibiotic Levels in Intensive Care (DALI) study was a
      prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic
      dosing was as per the treating clinician either by intermittent bolus or
      continuous infusion. Target trough concentration was defined as >=15 mg/L and
      target pharmacodynamic index was defined as an area under the concentration-time
      curve over a 24-hour period divided by the minimum inhibitory concentration of
      the suspected bacteria (AUC0-24/MIC ratio) >400 (assuming MIC <=1 mg/L). RESULTS:
      Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24
      patients received vancomycin by continuous infusion (57%). Daily dosage of
      vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different
      between patients receiving intermittent or continuous infusion. Trough
      concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough
      concentrations were achieved in 57% of patients, but more frequently in patients
      receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0
      24/MIC ratio was reached more frequently in patients receiving continuous
      infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis
      with adjustment by the propensity score could not confirm continuous infusion as
      an independent predictor of an AUC0-24/MIC >400 (odds ratio (OR) 1.65, 95%
      confidence interval (CI) 0.2 to 12.0) or a Cmin >=15 mg/L (OR 1.8, 95% CI 0.4 to
      8.5). CONCLUSIONS: This study demonstrated large interindividual variability in
      vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients.
      These data suggests that a re-evaluation of current vancomycin dosing
      recommendations in critically ill patients is needed to more rapidly and
      consistently achieve sufficient vancomycin exposure.

PMID- 24887572
TI  - The role of copy-and-paste in the hospital electronic health record.

PMID- 24887571
TI  - Report of the NIH task force on research standards for chronic low back pain.
AB  - Despite rapidly increasing intervention, functional disability due to chronic low
      back pain (cLBP) has increased in recent decades. We often cannot identify
      mechanisms to explain the major negative impact cLBP has on patients' lives. Such
      cLBP is often termed nonspecific and may be due to multiple biologic and
      behavioral etiologies. Researchers use varied inclusion criteria, definitions,
      baseline assessments, and outcome measures, which impede comparisons and
      consensus. Therefore, NIH Pain Consortium charged a research task force to draft
      standards for research on cLBP. The resulting multidisciplinary panel recommended
      using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain
      intensity, pain interference, and physical function); use of a minimum data set
      to describe research participants (drawing heavily on the Patient Reported
      Outcomes Measurement Information System methodology); reporting "responder
      analyses" in addition to mean outcome scores; and suggestions for future research
      and dissemination. The Pain Consortium has approved the recommendations, which
      investigators should incorporate into NIH grant proposals. The research task
      force believes that these recommendations will advance the field, help resolve
      controversies, and facilitate future research addressing the genomic,
      neurological, and other mechanistic substrates of cLBP. We expect that the
      research task force recommendations will become a dynamic document and undergo
      continual improvement. PERSPECTIVE: A task force was convened by the NIH Pain
      Consortium with the goal of developing research standards for cLBP. The results
      included recommendations for definitions, a minimum data set, reporting outcomes,
      and future research. Greater consistency in reporting should facilitate
      comparisons among studies and the development of phenotypes.

PMID- 24887573
TI  - Resolving the molecular mechanism of cadherin catch bond formation.
AB  - Classical cadherin Ca(2+)-dependent cell-cell adhesion proteins play key roles in
      embryogenesis and in maintaining tissue integrity. Cadherins mediate robust
      adhesion by binding in multiple conformations. One of these adhesive states,
      called an X-dimer, forms catch bonds that strengthen and become longer lived in
      the presence of mechanical force. Here we use single-molecule force-clamp
      spectroscopy with an atomic force microscope along with molecular dynamics and
      steered molecular dynamics simulations to resolve the molecular mechanisms
      underlying catch bond formation and the role of Ca(2+) ions in this process. Our
      data suggest that tensile force bends the cadherin extracellular region such that
      they form long-lived, force-induced hydrogen bonds that lock X-dimers into
      tighter contact. When Ca(2+) concentration is decreased, fewer de novo hydrogen
      bonds are formed and catch bond formation is eliminated. 

PMID- 24887575
TI  - Stercoral colitis: a lethal disease-computed tomographic findings and clinical
      characteristic.
AB  - OBJECTIVE: The aim of this study was to describe the radiographic findings in
      stercoral colitis. METHODS: The computed tomographic scans and abdominal
      radiographs of 13 patients with surgically and pathologically confirmed stercoral
      colitis from 4 affiliated hospitals were reviewed by a board-certified abdominal
      radiologist blinded to the official imaging, surgical, and pathologic findings.
      RESULTS: The median age was 66 years. The patients presented mainly with
      constipation (100%) and an acute inflammatory process (85%); 5 patients (38%) had
      frank septic shock. Mortality was 46%. Imaging scans showed that the colon
      dilated proximally to the impaction site in 6 patients (50%). Other findings
      included fat stranding (100%), mucosal sloughing (58%), mesenteric hyperemia
      (58%), and extraluminal gas (17%). CONCLUSIONS: Computed tomography is an
      important diagnostic modality for stercoral colitis. The presence of a large
      fecaloma with distention of the affected colon and wall thickening and
      pericolonic fat stranding should alert radiologists and surgeons to the presence
      of this potentially fatal condition.

PMID- 24887574
TI  - Genetic factors underlying discordance in chromatin accessibility between
      monozygotic twins.
AB  - BACKGROUND: Open chromatin is implicated in regulatory processes; thus,
      variations in chromatin structure may contribute to variations in gene expression
      and other phenotypes. In this work, we perform targeted deep sequencing for open
      chromatin, and array-based genotyping across the genomes of 72 monozygotic twins
      to identify genetic factors regulating co-twin discordance in chromatin
      accessibility. RESULTS: We show that somatic mutations cause chromatin
      discordance mainly via the disruption of transcription factor binding sites.
      Structural changes in DNA due to C:G to A:T transversions are under purifying
      selection due to a strong impact on chromatin accessibility. We show that CpGs
      whose methylation is specifically regulated during cellular differentiation
      appear to be protected from high mutation rates of 5'-methylcytosines, suggesting
      that the spectrum of CpG variations may be shaped fully at the developmental
      level but not through natural selection. Based on the association mapping of
      within-pair chromatin differences, we search for cases in which twin siblings
      with a particular genotype had chromatin discordance at the relevant locus. We
      identify 1,325 chromatin sites that are differentially accessible, depending on
      the genotype of a nearby locus, suggesting that epigenetic differences can
      control regulatory variations via interactions with genetic factors. Poised
      promoters present high levels of chromatin discordance in association with either
      somatic mutations or genetic-epigenetic interactions. CONCLUSION: Our
      observations illustrate how somatic mutations and genetic polymorphisms may
      contribute to regulatory, and ultimately phenotypic, discordance.

PMID- 24887576
TI  - Computed tomography (CT) venography with dual-energy CT: low tube voltage and
      dose reduction of contrast medium for detection of deep vein thrombosis.
AB  - OBJECTIVES: To assess whether low-dose contrast medium and low-tube voltage
      computed tomography (CT) venography can be used for clinical diagnosis. METHODS:
      This prospective study included 63 patients who were randomized into 3 groups and
      administered contrast medium of either 600, 500, or 400 mg of iodine per kilogram
      (mgI/kg). All patients underwent dual-energy CT at either 80 or 135 kilovolt
      (peak) (kV[p]). Control images (120 kV[p]) were acquired from them and were
      compared with 80-kV(p) images. The mean CT values of the bilateral femoral and
      popliteal veins were compared. RESULTS: The mean CT values of the 80-kV(p) images
      were significantly higher than 120-kV(p) images for all doses. No significant
      difference was observed for the CT values of the 80-kV(p) images with the 400
      mgI/kg dose and the control images (600 mgI/kg at 120 kV[p]). CONCLUSIONS: Low
      tube voltage enabled a reduction of contrast medium to 400 mgI/kg for CT
      venography.

PMID- 24887577
TI  - Preoperative prediction model for conversion of laparoscopic to open
      cholecystectomy in patient with acute cholecystitis: based on clinical,
      laboratory, and CT parameters.
AB  - OBJECTIVE: To identify preoperative computed tomography (CT) predictors
      associated with conversion from laparoscopic to open cholecystectomy and to
      propose the risk scoring model for prediction of conversion by integrating
      clinical, laboratory, and CT parameters. METHODS: The institutional review board
      approved this retrospective study, and informed consent was waived. One hundred
      eighty-three patients who underwent a laparoscopic cholecystectomy for acute
      cholecystitis were evaluated for clinical, laboratory, and CT parameters.
      Associations between conversion and these parameters were assessed by using
      univariate and multivariate logistic regression analysis. The risk scoring model
      was devised using a regression coefficient-based scoring method. RESULTS:
      Conversion to open cholecystectomy was performed in 30 patients (17%).
      Multivariate analysis identified age older than 60 years, male, and
      pericholecystic fluid as independent predictors of conversion. The preoperative
      prediction model to calculate the risk score for conversion showed sensitivity of
      83% and specificity of 72%, with an area under the receiver operator curve of
      0.83. CONCLUSIONS: Pericholecystic fluid collection was the only CT parameter
      with clinical parameters of age older than 60 years and male in prediction for
      conversion in acute cholecystitis. The preoperative prediction model using these
      3 parameters can be adapted easily in clinical practice with a good
      discrimination.

PMID- 24887578
TI  - Malignant renal epithelioid angiomyolipoma with liver metastasis after resection:
      a case report with multimodality imaging and review of the literature.
AB  - Renal epithelioid angiomyolipoma (EAML) is a perivascular epithelioid cell tumor.
      Although the overwhelming majority of renal EAMLs are benign, cases of aggressive
      behavior and malignancy have been reported. Here, we report the case of a 62-year
      old woman with a 12.5-cm renal EAML, who underwent resection and developed a 10.5
      cm hepatic EAML 15 months after the surgery. Although multicentric disease is a
      possibility, the temporal course is consistent with metastasis from the poorly
      differentiated primary tumor. This is the only report with multimodality imaging
      to detail new metastatic disease during surveillance after intended curative
      resection of an EAML. 

PMID- 24887579
TI  - Associations between seattle heart failure model scores and medical resource use
      and costs: findings from HF-ACTION.
AB  - BACKGROUND: Prognostic models, such as the Seattle Heart Failure Model (SHFM),
      have been developed to predict patient survival. The extent to which they predict
      medical resource use and costs has not been explored. In this study, we evaluated
      relationships between baseline SHFM scores and 1-year resource use and costs
      using data from a clinical trial. METHODS AND RESULTS: We applied generalized
      linear models to examine the relative impact of a 1-unit increase in SHFM scores
      on counts of medical resource use and direct medical costs at 1 year of follow
      up. Of 2331 randomized patients, 2288 (98%) had a rounded integer SHFM score
      between -1 and 2, consistent with predicted 1-year survival of 98% and 74%,
      respectively. At baseline, median age was 59 years, 28% of patients were women,
      and nearly two-thirds of the cohort had New York Heart Association class II heart
      failure and one-third had class III heart failure. Higher SHFM scores were
      associated with more hospitalizations (rate ratio per 1-unit increase, 1.86; P <
      .001), more inpatient days (2.30; P < .001), and higher inpatient costs (2.28; P
      < .001), outpatient costs (1.54; P < .001), and total medical costs (2.13; P <
      .001). CONCLUSION: Although developed to predict all-cause mortality, SHFM scores
      also predict medical resource use and costs.

PMID- 24887581
TI  - Potential protection of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside
      against staurosporine-induced toxicity on cultured rat hippocampus neurons.
AB  - The present study explored the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d
      glucoside (THSG) on the staurosporine (STS)-induced toxicity in cultured rat
      hippocampal neurons. The results showed that administration of 200MUM of THSG
      significantly protected against 0.3MUM of STS-induced apoptosis in cultured rat
      hippocampal neurons tested by methyl thiazolyl tetrazolium (MTT) and terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays.
      Furthermore, when the Akt signaling pathway was blocked by LY294002, an inhibitor
      of Phosphatidyl Inositol 3-kinase (PI3K), the protective effects of THSG against
      STS-induced neurotoxicity were abrogated. We further examined the involvement of
      PI3K/Akt signaling pathway in THSG protection against STS-induced cytotoxicity on
      cultured neurons and found that administration of THSG significantly inhibited
      the STS-induced decreases in the content of phosphorylated AKt (p-Akt). Moreover,
      we found that THSG rescued the down-regulation of B cell lymphoma/lewkmia-2
      (Bcl2) and pro-caspase-3 (pro-Csp3) caused by STS in the neurons. These results
      indicate that THSG protect the cultured rat hippocampal neurons against STS
      induced cytotoxicity and the PI3K/Akt signaling and mitochondrial apoptotic
      pathways are involved in the THSG-induced protective effects. 

PMID- 24887582
TI  - Effect of inactivation of the intermediate cerebellum on overground locomotion in
      the rat: a comparative study of the anterior and posterior lobes.
AB  - The importance of the cerebellum in control of locomotion is demonstrated by the
      ataxic gait of cerebellar patients. The intermediate cerebellum contains
      somatotopical representations for forelimbs and hindlimbs in both anterior and
      posterior lobes. However, it is not known whether these separate regions have
      discrete roles in control of limb movements during locomotion. Here we compared
      the effect of muscimol-induced inactivation of the anterior or posterior
      intermediate cerebellum on limb movements in walking rats. Inactivation of the
      anterior intermediate cerebellum had clear effects on limb movements during
      overground locomotion, resulting in excessive toe elevation and hyperflexion of
      joints in the swing phase. Inactivation of the posterior region resulted in
      similar but less pronounced deficits. Postural defects were not present in either
      group of rats. These findings suggest that the intermediate cerebellum of the
      anterior lobe has a greater influence on the ability to control limb movements
      during overground locomotion than the posterior lobe. 

PMID- 24887580
TI  - Alterations of gene expression and protein synthesis in co-cultured adipose
      tissue-derived stem cells and squamous cell-carcinoma cells: consequences for
      clinical applications.
AB  - INTRODUCTION: This is the first study evaluating the interactions of human
      adipose tissue derived stem cells (ADSCs) and human squamous cell carcinoma cells
      (SCCs), with regard to a prospective cell-based skin regenerative therapy and a
      thereby unintended co-localization of ADSCs and SCCs. METHODS: ADSCs were co
      cultured with A431-SCCs and primary SCCs (pSCCs) in a transwell system, and cell
      cell interactions were analyzed by assessing doubling time, migration and
      invasion, angiogenesis, quantitative real time PCR of 229 tumor associated genes,
      and multiplex protein assays of 20 chemokines and growth factors and eight matrix
      metalloproteinases (MMPS). Results of co-culture were compared to those of the
      respective mono-culture. RESULTS: ADSCs' proliferation on the plate was
      significantly increased when co-cultured with A431-SCCs (P = 0.038). PSCCs and
      ADSCs significantly decreased their proliferation in co-culture if cultured on
      the plate (P <0.001 and P = 0.03). The migration of pSCC was significantly
      increased in co-culture (P = 0.009), as well as that of ADSCs in A431-SCC-co
      culture (P = 0.012). The invasive behavior of pSCCs and A431-SCCs was
      significantly increased in co-culture by a mean of 33% and 35%, respectively (P =
      0.038 and P <0.001). Furthermore, conditioned media from co-cultured ADSC-A431
      SCCs and co-cultured ADSCs-pSCCs induced tube formation in an angiogenesis assay
      in vitro. CONCLUSIONS: This is the first study evaluating the possible
      interactions of primary human ADSCs with human SCCs, pointing towards a
      doubtlessly increased oncological risk, which should not be neglected when
      considering a clinical use of isolated human ADSCs in skin regenerative
      therapies.

PMID- 24887584
TI  - APOE E4 polymorphism and cognitive deficit among the very old Chinese veteran men
      without dementia.
AB  - Apolipoprotein E (APOE) gene polymorphism has been reported to be associated with
      cognitive dysfunction in healthy individuals, however the results were
      controversial in the very old elderly. The aim of this study is to assess the
      possible association of the APOE polymorphism with cognitive dysfunction in
      people aged 75 years and over. Four hundred and twenty-five aged Chinese veteran
      men without dementia were enrolled for APOE genotyping and neuropsychological
      tests including Mini-Mental Status Examination (MMSE), Digit Span Forward and
      Backward, and Cognitive Ability Screening Instrument Chinese language version
      (CASI C-2.0) were evaluated in these subjects. Among the elderly veterans, people
      who carry APOE E4 were found to have worse performance on the total CASI scores,
      the abstraction/judgment subscores and the list-generating fluency subscores.
      This study suggests that the APOE E4 alleles contributed detrimental effects on
      cognitive function in the very old veterans who do not have dementia. 

PMID- 24887583
TI  - p-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice.
AB  - Alzheimer's disease (AD) is a proteinopathy characterized by the accumulation of
      beta-amyloid (Abeta) and tau. To date, clinical trials indicate that Abeta
      immunotherapy does not improve cognition. Consequently, it is critical to
      modulate other aspects of AD pathology. As such, tau represents an excellent
      target, as its accumulation better correlates with cognitive impairment. To
      determine the effectiveness of targeting pathological tau, with Abeta pathology
      present, we administered a single injection of AT8, or control antibody, into the
      hippocampus of aged 3xTg-AD mice. Extensive data indicates that phosphorylated
      Ser(202) and Thr(205) sites of tau (corresponding to the AT8 epitope) represent a
      pathologically relevant target for AD. We report that immunization with AT8
      reduced somatodendritic tau load, p-tau immunoreactivity, and silver stained
      positive neurons, without affecting Abeta pathology. We also discovered that tau
      pathology soon reemerges post-injection, possibly due to persistent Abeta
      pathology. These studies provide evidence that targeting p-tau may represent an
      effective treatment strategy: potentially in conjunction with Abeta
      immunotherapy. 

PMID- 24887585
TI  - Simple and difficult mathematics in children: a minimum spanning tree EEG network
      analysis.
AB  - Sensor-level network characteristics associated with arithmetic tasks varying in
      complexity were estimated using tools from modern network theory. EEG signals
      from children with math difficulties (MD) and typically achieving controls (NI)
      were analyzed using minimum spanning tree (MST) indices derived from Phase Lag
      Index values - a graph method that corrects for comparison bias. Results
      demonstrated progressive modulation of certain MST parameters with increased task
      difficulty. These findings were consistent with more distributed network
      activation in the theta band, and greater network integration (i.e., tighter
      communication between involved regions) in the alpha band as task demands
      increased. There was also evidence of stronger intraregional signal inter
      dependencies in the higher frequency bands during the complex math task. Although
      these findings did not differ between groups, several MST parameters were
      positively correlated with individual performance on psychometric math tasks
      involving similar operations, especially in the NI group. The findings support
      the potential utility of MST analyses to evaluate function-related
      electrocortical reactivity over a wide range of EEG frequencies in children. 

PMID- 24887588
TI  - Asymmetric organocatalytic desymmetrization of 4,4-disubstituted
      cyclohexadienones at high pressure: a new powerful strategy for the synthesis of
      highly congested chiral cyclohexenones.
AB  - A highly diastereoselective and enantioselective method for the asymmetric
      desymmetrization of 4,4-disubstituted cyclohexadienones using the Michael
      addition reaction of malonates under catalysis with the primary amine-thiourea
      conjugate catalyst and PPY at high pressure was developed. 

PMID- 24887586
TI  - The effect of health-facility admission and skilled birth attendant coverage on
      maternal survival in India: a case-control analysis.
AB  - BACKGROUND: Research in areas of low skilled attendant coverage found that
      maternal mortality is paradoxically higher in women who seek obstetric care. We
      estimated the effect of health-facility admission on maternal survival, and how
      this effect varies with skilled attendant coverage across India.
      METHODS/FINDINGS: Using unmatched population-based case-control analysis of
      national datasets, we compared the effect of health-facility admission at any
      time (antenatal, intrapartum, postpartum) on maternal deaths (cases) to women
      reporting pregnancies (controls). Probability of maternal death decreased with
      increasing skilled attendant coverage, among both women who were and were not
      admitted to a health-facility, however, the risk of death among women who were
      admitted was higher (at 50% coverage, OR = 2.32, 95% confidence interval 1.85
      2.92) than among those women who were not; while at higher levels of coverage,
      the effect of health-facility admission was attenuated. In a secondary analysis,
      the probability of maternal death decreased with increasing coverage among both
      women admitted for delivery or delivered at home but there was no effect of
      admission for delivery on mortality risk (50% coverage, OR = 1.0, 0.80-1.25),
      suggesting that poor quality of obstetric care may have attenuated the benefits
      of facility-based care. Subpopulation analysis of obstetric hemorrhage cases and
      report of 'excessive bleeding' in controls showed that the probability of
      maternal death decreased with increasing skilled attendant coverage; but the
      effect of health-facility admission was attenuated (at 50% coverage, OR = 1.47,
      0.95-1.79), suggesting that some of the effect in the main model can be explained
      by women arriving at facility with complications underway. Finally, highest risk
      associated with health-facility admission was clustered in women with education
      <= 8 years. CONCLUSIONS: The effect of health-facility admission did vary by
      skilled attendant coverage, and this effect appears to be driven partially by
      reverse causality; however, inequitable access to and possibly poor quality of
      healthcare for primary and emergency services appears to play a role in maternal
      survival as well.

PMID- 24887587
TI  - NT5E mutations that cause human disease are associated with intracellular
      mistrafficking of NT5E protein.
AB  - Ecto-5'-nucleotidase/CD73/NT5E, the product of the NT5E gene, is the dominant
      enzyme in the generation of adenosine from degradation of AMP in the
      extracellular environment. Nonsense (c.662C->A, p.S221X designated F1,
      c.1609dupA, p.V537fsX7 designated F3) and missense (c.1073G->A, p.C358Y
      designated F2) NT5E gene mutations in three distinct families have been shown
      recently to cause premature arterial calcification disease in human patients.
      However, the underlying mechanisms by which loss-of-function NT5E mutations cause
      human disease are unknown. We hypothesized that human NT5E gene mutations cause
      mistrafficking of the defective proteins within cells, ultimately blocking NT5E
      catalytic function. To test this hypothesis, plasmids encoding cDNAs of wild type
      and mutant human NT5E tagged with the fluorescent probe DsRed were generated and
      used for transfection and heterologous expression in immortalized monkey COS-7
      kidney cells that lack native NT5E protein. Enzyme histochemistry and Malachite
      green assays were performed to assess the biochemical activities of wild type and
      mutant fusion NT5E proteins. Subcellular trafficking of fusion NT5E proteins was
      monitored by confocal microscopy and western blot analysis of fractionated cell
      constituents. All 3 F1, F2, and F3 mutations result in a protein with
      significantly reduced trafficking to the plasma membrane and reduced ER retention
      as compared to wild type protein. Confocal immunofluorescence demonstrates
      vesicles containing DsRed-tagged NT5E proteins (F1, F2 and F3) in the cell
      synthetic apparatus. All 3 mutations resulted in absent NT5E enzymatic activity
      at the cell surface. In conclusion, three familial NT5E mutations (F1, F2, F3)
      result in novel trafficking defects associated with human disease. These novel
      genetic causes of human disease suggest that the syndrome of premature arterial
      calcification due to NT5E mutations may also involve a novel "trafficking
      opathy". 

PMID- 24887589
TI  - ATL-1, a synthetic analog of lipoxin, modulates endothelial permeability and
      interaction with tumor cells through a VEGF-dependent mechanism.
AB  - Lipoxins (LX) and 15-epi-LX are lipids with a potent inhibitory effect on
      angiogenesis, in different models in vivo and in vitro. ATL-1, a synthetic analog
      of 15-epi-LXA4, inhibits various actions stimulated by vascular endothelial
      growth factor (VEGF). However, LX actions on endothelial cells (EC) in tumor
      related contexts are still unknown. Here, we investigated the modulation of EC by
      ATL-1, in a model that mimics tumor extravasation. We observed that the analog
      inhibited endothelial permeability induced by VEGF, through the stabilization of
      VE-cadherin/beta-catenin-dependent adherens junctions. We tested the ability of
      MV3 cells, a highly metastatic melanoma cell line, to transmigrate across
      unchallenged EC monolayers for 18 h, as compared to NGM normal melanocytes. ATL-1
      was able to inhibit only melanoma extravasation. MV3 cells secrete large amounts
      of VEGF and we observed that ATL-1 per se did not alter this ability. Melanoma
      cells skills to crossing endothelial monolayers were due to the steady
      accumulation of tumor-derived VEGF. When endothelial cells were challenged with
      exogenous VEGF, added at levels comparable to those secreted by MV3 cells over 18
      h, and a short-term (4h) transendothelial migration assay was performed, both
      melanoma and melanocyte cells were able to extravasate, and ATL-1 was able to
      block the passage of both cells. These results indicate that ATL-1 has a potent
      inhibitory effect on the permeability induced by VEGF, and that this
      pharmacological effect could be used to block tumor extravasation across
      endothelial barriers, with a possible prospect of reducing the haematogenic
      spread of cancer cells.

PMID- 24887590
TI  - Triangular gold nanoparticles conjugated with peptide ligands: a new class of
      inhibitor for Candida albicans secreted aspartyl proteinase.
AB  - The aim of this study was to find the peptide ligands to inhibit Candida albicans
      secreted aspartyl proteinase 2 (Sap2). First, a ligand library, containing 300
      different peptides, was constructed, and their interaction with Sap2 was
      separately calculated by molecular dynamic software. Second, 10 peptide ligands
      with the lowest intermolecular energy were selected. Then, triangular gold
      nanoparticles were synthesized, and separately conjugated with the peptide
      ligands. After synthesis, antifungal property and Sap inactivation of conjugated
      triangular gold nanoparticles, peptide ligands, and naked triangular gold
      nanoparticle were separately assessed, against thirty clinical isolates of C.
      albicans. In this study, we measured the uptake of conjugated and naked
      nanoparticles by atomic adsorption spectroscopy. This study showed that naked
      triangular gold nanoparticle and all conjugated triangular gold nanoparticles had
      high antifungal activity, but no peptide ligands had such activity. Of 300
      peptide ligands, the peptide containing N-Cys-Lys-Lys-Arg-Met-Met-Lys-Ser-Met-Cys
      C and its conjugate had the highest capability to inhibit Sap. Moreover, the
      uptake assay demonstrated that triangular gold nanoparticles conjugated with the
      peptide ligand had the highest uptake. 

PMID- 24887591
TI  - Effect of joint mechanism on vehicle redirectional capability of water-filled
      road safety barrier systems.
AB  - Portable water-filled barriers (PWFBs) are roadside appurtenances that prevent
      vehicles from penetrating into temporary construction zones on roadways. PWFBs
      are required to satisfy the strict regulations for vehicle re-direction in tests.
      However, many of the current PWFBs fail to re-direct the vehicle at high speeds
      due to the inability of the joints to provide appropriate stiffness. The joint
      mechanism hence plays a crucial role in the performance of a PWFB system at high
      speed impacts. This paper investigates the desired features of the joint
      mechanism in a PWFB system that can re-direct vehicles at high speeds, while
      limiting the lateral displacement to acceptable limits. A rectangular "wall"
      representative of a 30m long barrier system was modeled and a novel method of
      joining adjacent road barriers was introduced through appropriate pin-joint
      connections. The impact response of the barrier "wall" and the vehicle was
      obtained and the results show that a rotational stiffness of 3000kNm/rad at the
      joints seems to provide the desired features of the PWFB system to re-direct
      impacting vehicles and restrict the lateral deflection. These research findings
      will be useful to safety engineers and road barrier designers in developing a new
      generation of PWFBs for increased road safety. 

PMID- 24887592
TI  - Development and validation of an ultra high performance liquid chromatography
      tandem mass spectrometry method for simultaneous determination of sulfonamides,
      quinolones and benzimidazoles in bovine milk.
AB  - A simple, sensitive and reliable analytical method was developed for the
      simultaneous determination of 38 veterinary drugs (18 sulfonamides, 11 quinolones
      and 9 benzimidazoles) and 8 metabolites of benzimidazoles in bovine milk by ultra
      high performance liquid chromatography-positive electrospray ionization tandem
      mass spectrometry (UHPLC-ESI-MS/MS). Samples were extracted with acidified
      acetonitrile, cleaned up with Oasis((r)) MCX cartridges, and analyzed by LC-MS/MS
      on an Acquity UPLC((r)) BEH C18 column with gradient elution. The method allows
      such multi-analyte measurements within a 13min runtime while the specificity is
      ensured through the MRM acquisition mode. The method was validated according to
      the European Commission Decision 2002/657/EC determining specificity, decision
      limit (CCalpha), detection capability (CCbeta), recovery, precision, linearity
      and stability. For compounds which have MRLs in bovine milk, the CCalpha values
      fall into a range from 11 to 115MUg/kg, and the CCbeta values fall within a range
      of 12-125MUg/kg. For compounds which have not MRLs in bovine milk, the CCalpha
      values fall into a range from 0.01 to 0.08MUg/kg, and the CCbeta values fall
      within a range of 0.02-0.11MUg/kg. The mean recoveries of the 46 analytes were
      between 87 and 119%. The calculated RSD values of repeatability and within
      laboratory reproducibility experiments were below 11% and 15% for the 46
      compounds, respectively. The method was demonstrated to be suitable for the
      simultaneous determination of sulfonamides, quinolones and benzimidazoles in
      bovine milk. 

PMID- 24887593
TI  - Protocol for simultaneous isolation of three important banana allergens.
AB  - Banana fruit (Musa acuminata) has become an important food allergen source in
      recent years. So far, 5 IgE reactive banana proteins have been identified, and
      the major allergens are: Mus a 2 (a class I chitinase, 31kDa), Mus a 4 (thaumatin
      like protein, 21kDa), and Mus a 5 (beta-1,3-glucanase, 33kDa). Due to variations
      in allergen expression levels, diagnostic reagents for food allergy can be
      improved by using individual allergen components instead of banana allergen
      extracts. The purpose of this study was to optimize the purification protocol of
      the three major allergens present in banana fruit: Mus a 2, Mus a 4 and Mus a 5.
      By employing a three-step purification protocol (a combination of anion-exchange,
      cation-exchange and reversed-phase chromatography) three important banana
      allergens were obtained in sufficient yield and high purity. Characterization of
      the purified proteins was performed by both biochemical (2-D PAGE, mass
      fingerprint and N-terminal sequencing) and immunochemical (immunoblot) methods.
      IgE reactivity to the purified allergens was tested by employing sera of five
      allergic patients. The purified allergens displayed higher sensitivity in IgE
      detection than the routinely used extracts. The three purified allergens are good
      candidates for reagents in component-based diagnosis of banana allergy. 

PMID- 24887594
TI  - Identification of the bioactive components of orally administered Lithocarpus
      polystachyus Rehd and their metabolites in rats by liquid chromatography coupled
      to LTQ Orbitrap mass spectrometry.
AB  - A rapid, sensitive and selective UPLC/MS method using LTQ Orbitrap mass
      spectrometry was established for the analysis and characterization of the main
      biological components and their metabolites in rat plasma, urine and feces
      following oral administration of Lithocarpus polystachyus extract. In vivo, 22
      flavonoid metabolites were observed in rat plasma, and 13 metabolites were
      detected in rat urine, whereas just two aglycones of dihydrochalcone (3-hydroxy
      phloretin and phloretin) could be detected in rat feces. Among these metabolites,
      one new and a known dihydrochalcone metabolite were isolated and definitely
      identified. Besides, five dihydrochalcone metabolites were tentatively identified
      as new compounds. A metabolism study of 3-hydroxyphlorizin and phloridzin was
      also conducted. Glucuronidation was the main metabolic pathway of phloridzin,
      whereas glucuronidation and sulfonation were the main metabolic pathway of 3
      hydroxyphlorizin. These results provided a basis for evaluating the bioactive
      components of a complex natural medicine and their mechanisms of actions. 

PMID- 24887596
TI  - Aqueous solutions of tetraalkylammonium halides: ion hydration, dynamics and ion
      ion interactions in light of steric effects.
AB  - Molecular simulations have allowed us to probe the atomic details of aqueous
      solutions of tetramethylammonium (TMA) and tetrabutylammonium (TBA) bromide,
      across a wide range of concentrations (0.5 to 3-4 molal). We highlight the space
      filling (TMA(+)) versus penetrable (TBA(+)) nature of these polyatomic cations
      and its consequence for ion hydration, ion dynamics and ion-ion interactions. A
      well-established hydration is seen for both TMA(+) and TBA(+) throughout the
      concentration range studied. A clear penetration of water molecules, as well as
      counterions, between the hydrocarbon arms of TBA(+), which remain in an extended
      configuration, is seen. Global rotation of individual TBA(+) points towards
      isolated rather than aggregated ions (from dilute up to 1 m concentration). Only
      for highly concentrated solutions, in which inter-penetration of adjacent TBA(+)s
      cannot be avoided, does the rotational time increase dramatically. From both
      structural and dynamic data we conclude that there is absence of hydrophobicity
      driven cation-cation aggregation in both TMABr and TBABr solutions studied. The
      link between these real systems and the theoretical predictions for spherical
      hydrophobic solutes of varying size does not seem straightforward. 

PMID- 24887595
TI  - How does the suppression of energy supplementation affect herbage intake,
      performance and parasitism in lactating saddle mares?
AB  - Agroecology opens up new perspectives for the design of sustainable farming
      systems by using the stimulation of natural processes to reduce the inputs needed
      for production. In horse farming systems, the challenge is to maximize the
      proportion of forages in the diet, and to develop alternatives to synthetic
      chemical drugs for controlling gastrointestinal nematodes. Lactating saddle
      mares, with high nutritional requirements, are commonly supplemented with
      concentrates at pasture, although the influence of energy supplementation on
      voluntary intake, performance and immune response against parasites has not yet
      been quantified. In a 4-month study, 16 lactating mares experimentally infected
      with cyathostome larvae either received a daily supplement of barley (60% of
      energy requirements for lactation) or were non-supplemented. The mares were
      rotationally grazed on permanent pastures over three vegetation cycles. All the
      mares met their energy requirements and maintained their body condition score
      higher than 3. In both treatments, they produced foals with a satisfying growth
      rate (cycle 1: 1293 g/day; cycle 2: 1029 g/day; cycle 3: 559 g/day) and
      conformation (according to measurements of height at withers and cannon bone
      width at 11 months). Parasite egg excretion by mares increased in both groups
      during the grazing season (from 150 to 2011 epg), independently of whether they
      were supplemented or not. This suggests that energy supplementation did not
      improve mare ability to regulate parasite burden. Under unlimited herbage
      conditions, grass dry matter intake by supplemented mares remained stable around
      22.6 g DM/kg LW per day (i.e. 13.5 kg DM/al per day), whereas non-supplemented
      mares increased voluntary intake from 22.6 to 28.0 g DM/kg LW per day (13.5 to
      17.2 kg DM/al per day) between mid-June and the end of August. Hence total
      digestible dry matter intake and net energy intake did not significantly differ
      between supplemented and non-supplemented mares during the second and third
      cycles. In conclusion, supplementing lactating mares at pasture should not be
      systematic because their adaptive capacities enable to increase herbage intake
      and ensure foal growth. Further research is needed to determine the herbage
      allowance threshold below which supplementation is required. 

PMID- 24887597
TI  - Evidence for a difference in rupture initiation between small and large
      earthquakes.
AB  - The process of earthquake rupture nucleation and propagation has been
      investigated through laboratory experiments and theoretical modelling, but a
      limited number of observations exist at the scale of earthquake fault zones.
      Distinct models have been proposed, and whether the magnitude can be predicted
      while the rupture is ongoing represents an unsolved question. Here we show that
      the evolution of P-wave peak displacement with time is informative regarding the
      early stage of the rupture process and can be used as a proxy for the final size
      of the rupture. For the analysed earthquake set, we found a rapid initial
      increase of the peak displacement for small events and a slower growth for large
      earthquakes. Our results indicate that earthquakes occurring in a region with a
      large critical slip distance have a greater likelihood of growing into a large
      rupture than those originating in a region with a smaller slip-weakening
      distance. 

PMID- 24887598
TI  - Application of subhairline EEG montage in intensive care unit: comparison with
      full montage.
AB  - PURPOSE: Problems with the availability of standard EEG monitoring in the
      intensive care unit have led to the use of recordings that have limited spatial
      coverage. We studied the performance of limited coverage EEG compared with more
      traditional full-montage EEG. METHODS: Continuous EEG recordings were performed
      on 170 patients using the full-montage 10-20 placement of electrodes as a
      reference recording and an abbreviated montage of electrodes applied below the
      hairline (subhairline). Recordings were reviewed independently, with the identity
      of the patients concealed. RESULTS: Seizures were found in 8% of patients.
      Sensitivity for detecting patients with seizures using the subhairline system was
      0.54 [95% confidence interval (95% CI), 0.29-0.77] with specificity of 1.00 (95%
      CI, 0.97-1.00) and positive predictive value of 1.00 (95% CI, 0.65-1.00). For
      detecting interictal epileptiform activity, we found sensitivity to be 0.60 (95%
      CI, 0.46-0.74), specificity to be 0.94 (95% CI, 0.88-0.97), and positive
      predictive value to be 0.81 (95% CI, 0.65-0.91). Performance was poor for
      triphasic waves, alpha/theta/spindle coma, and suppression. CONCLUSIONS: The
      subhairline montage shows excellent specificity for detecting patients with
      seizure activity but has limited sensitivity. It has relatively poor performance
      for other EEG phenomena, but further applications in trending and assessing
      reactivity should be assessed in further studies.

PMID- 24887599
TI  - Integration of EEG lead placement templates into traditional technologist-based
      staffing models reduces costs in continuous video-EEG monitoring service.
AB  - PURPOSE: The purpose of this study was to determine the relative cost reductions
      within different staffing models for continuous video-electroencephalography
      (cvEEG) service by introducing a template system for 10/20 lead application.
      METHODS: We compared six staffing models using decision tree modeling based on
      historical service line utilization data from the cvEEG service at our center.
      Templates were integrated into technologist-based service lines in six different
      ways. The six models studied were templates for all studies, templates for
      intensive care unit (ICU) studies, templates for on-call studies, templates for
      studies of <= 24-hour duration, technologists for on-call studies, and
      technologists for all studies. RESULTS: Cost was linearly related to the study
      volume for all models with the "templates for all" model incurring the lowest
      cost. The "technologists for all" model carried the greatest cost. Direct cost
      comparison shows that any introduction of templates results in cost savings, with
      the templates being used for patients located in the ICU being the second most
      cost efficient and the most practical of the combined models to implement. Cost
      difference between the highest and lowest cost models under the base case
      produced an annual estimated savings of $267,574. Implementation of the ICU
      template model at our institution under base case conditions would result in a
      $205,230 savings over our current "technologist for all" model. CONCLUSIONS: Any
      implementation of templates into a technologist-based cvEEG service line results
      in cost savings, with the most significant annual savings coming from using the
      templates for all studies, but the most practical implementation approach with
      the second highest cost reduction being the template used in the ICU. The lowered
      costs determined in this work suggest that a template-based cvEEG service could
      be supported at smaller centers with significantly reduced costs and could allow
      for broader use of cvEEG patient monitoring.

PMID- 24887600
TI  - De novo generalized periodic discharges related to anesthetic withdrawal resolve
      spontaneously.
AB  - Pentobarbital and propofol are used for the treatment of refractory status
      epilepticus or elevated intracranial pressure, typically with continuous EEG
      monitoring. We report a series of patients who developed generalized periodic
      discharges related to anesthetic withdrawal (GRAWs), different from previous
      seizure activity. At times, this pattern was misinterpreted as recurrent seizure
      activity, leading to reinstitution of drug-induced coma, but resolved
      spontaneously without additional treatment.We identified five patients who
      developed GRAWs during pentobarbital or propofol withdrawal. Two patients
      received pentobarbital for increased intracranial pressure. One patient received
      pentobarbital and propofol for encephalopathy accompanied by a rhythmic EEG
      pattern erroneously thought to be ictal. Two patients received pentobarbital for
      refractory partial status epilepticus. In all cases, anesthetic agents were
      withdrawn after 24 to 48 hours of burst suppression on EEG. We analyzed the
      course of GRAWs on EEG and the associated clinical outcomes.All five patients
      developed GRAWs, consisting of periodic 1 to 4 Hz generalized periodic discharge,
      not previously seen on EEG. In all cases, the pattern eventually resolved
      spontaneously, over 12 to 120 hours. However, in three cases, the pattern was
      initially thought to represent ictal activity, and drug-induced coma was
      reinitiated. The pattern recurred during repeated anesthetic withdrawal, was then
      recognized as nonictal, and then resolved without further treatment. In all cases
      but one, the patients exhibited improvement to near-baseline
      mentation.Generalized periodic discharges related to anesthetic withdrawal may
      occur de novo after pentobarbital or propofol withdrawal. They should resolve
      spontaneously without treatment and without recurrence of clinical seizure
      activity. However, GRAWs are not likely to represent status epilepticus and
      should not prompt resumption of drug-induced coma, unless there is reappearance
      of original electrographic seizure activity.

PMID- 24887602
TI  - Simultaneous recording of EEG and electromyographic polygraphy increases the
      diagnostic yield of video-EEG monitoring.
AB  - PURPOSE: To investigate the usefulness of adjunctive electromyographic (EMG)
      polygraphy in the diagnosis of clinical events captured during long-term video
      EEG monitoring. METHODS: A total of 40 patients (21 women, 19 men) aged between
      19 and 72 years (mean 43) investigated using video-EEG monitoring were studied.
      Electromyographic activity was simultaneously recorded with EEG in four patients
      selected on clinical grounds. In these patients, surface EMG electrodes were
      placed over muscles suspected to be activated during a typical clinical event.
      RESULTS: Of the 40 patients investigated, 24 (60%) were given a diagnosis,
      whereas 16 (40%) remained undiagnosed. All four patients receiving adjunctive EMG
      polygraphy obtained a diagnosis, with three of these diagnoses being exclusively
      reliant on the EMG recordings. Specifically, one patient was diagnosed with
      propriospinal myoclonus, another patient was diagnosed with facio-mandibular
      myoclonus, and a third patient was found to have bruxism and periodic leg
      movements of sleep. CONCLUSIONS: The information obtained from surface EMG
      recordings aided the diagnosis of clinical events captured during video-EEG
      monitoring in 7.5% of the total cohort. This study suggests that EEG-EMG
      polygraphy may be used as a technique of improving the diagnostic yield of video
      EEG monitoring in selected cases.

PMID- 24887601
TI  - Diagnostic outcome of surgical revision of intracranial electrode placements for
      seizure localization.
AB  - PURPOSE: We aimed to determine the yield of revising intracranially implanted
      electrodes and the factors contributing to the yield. METHODS: Patients were
      identified from the Mayo Clinic Epilepsy Surgery Database between 1997 and 2010.
      Twenty patients had revision of intracranial electrode placements because initial
      implantation did not localize seizure onset adequately. RESULTS: Seizures were
      captured in 18 of 20 patients who underwent intracranial electrode revision, of
      which 10 (55.6%) showed localized seizure onset that led to a surgical resection.
      Seizures were improved in 9 of 10 patients who underwent resection; of these,
      five were seizure free. The only factors found to be statistically significant in
      localizing ictal onset zone after revised implantation were prior focal scalp
      interictal discharges and an initial intracranial EEG showing ictal onset at the
      edge of the electrode grid. No permanent complication was associated with revised
      implantation, but one patient had transient apraxia of the right foot.
      CONCLUSIONS: Revised implantation could be useful in selected patients with
      inadequate seizure localization on initial intracranial EEG. Resective surgery
      was performed in 50% of patients who underwent revision of intracranial
      electrodes with the majority of these patients experiencing an improvement in
      seizure control.

PMID- 24887603
TI  - Atypical cortical language organization in epilepsy patients: evidence for
      divergent hemispheric dominance for receptive and expressive language function.
AB  - The central goal of presurgical language mapping is to identify brain regions
      that subserve cortical language function to minimize postsurgical language
      deficits. Presurgical language mapping in patients with epilepsy presents a key
      challenge because of the atypical pattern of hemispheric language dominance found
      in this population, with higher incidences of bilateral and right-biased language
      dominance than typical. In this prospective study, we combine
      magnetoencephalography with a panel of tasks designed to separately assess
      receptive and expressive function to provide a sensitive measure of language
      function in 15 candidates for resective surgery. We report the following: 4 of 15
      patients (27%) showed left hemisphere dominance across all tasks, 4 of 15
      patients (27%) showed right hemisphere dominance across all tasks, and 7 of 15
      (46%) showed discordant language dominance, with right-dominant receptive and
      left-dominant expressive language. All patients with discordant language
      dominance showed this right-receptive and left-expressive pattern. Results
      provide further evidence supporting the importance of using a panel of tasks to
      assess separable aspects of language function. The clinical relevance of the
      findings is discussed, especially about current clinical operative measures for
      assessing language dominance, which use single hemisphere procedure (intracarotid
      amobarbital procedure and awake intraoperative stimulation) for determining
      language laterality.

PMID- 24887604
TI  - Electroencephalography-based real-time cortical monitoring system that uses
      hierarchical Bayesian estimations for the brain-machine interface.
AB  - In this study, a real-time cortical activity monitoring system was constructed,
      which could estimate cortical activities every 125 milliseconds over 2,240
      vertexes from 64 channel electroencephalography signals through the Hierarchical
      Bayesian estimation that uses functional magnetic resonance imaging data as its
      prior information. Recently, functional magnetic resonance imaging has mostly
      been used in the neurofeedback field because it allows for high spatial
      resolution. However, in functional magnetic resonance imaging, the time for the
      neurofeedback information to reach the patient is delayed several seconds because
      of its poor temporal resolution. Therefore, a number of problems need to be
      solved to effectively implement feedback training paradigms in patients. To
      address this issue, this study used a new cortical activity monitoring system
      that improved both spatial and temporal resolution by using both functional
      magnetic resonance imaging data and electroencephalography signals in conjunction
      with one another. This system is advantageous as it can improve applications in
      the fields of real-time diagnosis, neurofeedback, and the brain-machine
      interface.

PMID- 24887605
TI  - Interventional neuroradiology cases with intraprocedural clots: initial
      experience.
AB  - OBJECTIVE: Intraprocedural clot formation is rare but potentially serious
      complication of interventional neuroradiology procedures. We investigate if
      intraoperative monitoring (IOM) has utility to detect such clots. Intraprocedural
      clot formation is a rare but potentially serious complication of interventional
      neuroradiology procedures. Intraoperative monitoring detected nearly half of the
      included cases first. All of the included patients without improvement of the IOM
      changes were discharged home at best severely disabled. METHODS: The study
      included patients with thromboembolic events during interventional neuroradiology
      cases at Barrow Neurologic Institute from 2006 to 2010, with prespecified
      outcomes. Electroneurodiagnostic recordings were reviewed. RESULTS: Twelve
      patients were included in this study. All showed changes in their IOM. Five
      showed a change in IOM recording before a change was seen on the angiogram. Two
      returned to baseline, four improved but not to baseline, and six did not improve
      at all. All six patients without IOM improvement were discharged at best severely
      disabled. Ten of the 12 patients with clots had a subarachnoid hemorrhage before
      treatment. CONCLUSIONS: Intraoperative monitoring recording may be a valuable
      tool in monitoring patients during endovascular treatment to identify
      intraprocedural thromboembolic events. Intraoperative monitoring may correlate
      with poor outcomes when the changed responses do not improve. These data might be
      important when determining how aggressive to be in treating intraprocedural
      clots. Electroneurodiagnostic seems to be particularly warranted in patients with
      subarachnoid hemorrhage before treatment. A larger study is needed to validate
      these findings.

PMID- 24887606
TI  - EEG asymmetry during aortic arch surgeries associated with selective preferential
      cerebral hypothermia.
AB  - Intraoperative EEG monitoring is increasingly used during aortic arch procedures
      for early detection of acute neurologic dysfunction. In those procedures
      involving cardiopulmonary bypass, increased neuroprotection may be gained by
      using hypothermic circulatory arrest and selective cerebral perfusion. Several
      techniques for cerebral perfusion exist; yet no studies have noted distinct EEG
      patterns associated with different techniques. In this study, we reviewed EEG
      records of six aortic arch procedures that used cannulation of the innominate
      artery to provide selective antegrade cerebral perfusion. In each case, a
      transient hemispheric asymmetry was noted within 2 minutes of the start of head
      cooling, consisting of enhanced suppression over the right compared with the left
      hemisphere, which was confirmed by power analysis. The EEG returned to baseline
      during passive-head rewarming in five cases, whereas a brief left-sided partial
      seizure occurred during rewarming in one case. These findings suggest that
      antegrade cerebral perfusion using cannulation of the innominate artery results
      in enhanced cooling of the right hemisphere as detected by intraoperative EEG
      monitoring. Characterization of this finding is necessary to prevent
      misinterpretation of ischemia by EEG.

PMID- 24887607
TI  - Dipole orientation of receptive fields in the somatosensory cortex after
      stimulation of the posterior tibial nerve in humans.
AB  - The origins of the earliest evoked potentials and magnetic fields after tibial
      nerve electrical stimulation are still controversial. We focused on the initial
      activity from the gyrus area and analyzed the components for the coronal and
      sagittal planes. In 12 healthy right-handed subjects, electrical stimuli were
      delivered to the left posterior tibial nerve at the ankle. The cortical
      somatosensory evoked fields were recorded, and the equivalent current dipoles
      were calculated and separated into the sagittal plane (y-components) and coronal
      plane (x-components) components. In nine subjects, we observed two deflections
      (y1 and y2) in the y-component waveform and two deflections (x1 and x2) in the x
      component waveform over 60 milliseconds; y1 was directed anteriorly, y2
      posteriorly, x1 to the left, and x2 to the right. The y1 was originated in the
      anterior wall of the central sulcus. By focusing on the y-component, we
      elucidated the existence of the posteroanterior component, which may originate
      from the area 3b (gyrus) in tibial nerve somatosensory evoked fields and has the
      same quality as N20m for median nerve somatosensory evoked fields. This is the
      first report to suggest that the posteroanterior component in the tibial nerve is
      analogous to N20m in the median nerve using magnetoencephalography.

PMID- 24887608
TI  - Somatosensory evoked potentials in chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - PURPOSE: Somatosensory evoked potentials (SEPs) offer complementary results to
      those of nerve conduction studies and contribute to the electrodiagnostic
      criteria of chronic inflammatory demyelinating polyradiculoneuropathy. METHODS:
      We performed nerve conduction studies and SEPs in patients with symmetrical motor
      weakness, areflexia, and/or sensory disturbances lasting for at least 8 weeks. We
      determined two groups according to the electrodiagnostic criteria of the European
      Federation of Neurological Societies. Group 1 included patients who met the
      definite or probable electrodiagnostic criteria, and group 2 included patients
      who met the possible electrodiagnostic criteria. We also compared SEPs results
      with those of controls (group of healthy subjects). RESULTS: Sixteen patients (14
      men; mean age, 59 +/- 17.3 years) were included in the study. The latencies of
      potentials N9, N13, N7, and N22 and the intervals N9-N13 and N7-N22 were
      significantly increased in patients compared with controls. The N9/iP14 amplitude
      ratio was significantly lower in patients. There was no significant difference in
      the latencies of SEPs between the two groups of patients. CONCLUSIONS: We confirm
      the contribution of SEPs as complementary information to nerve conduction studies
      in chronic inflammatory demyelinating polyradiculoneuropathy diagnosis. In
      addition to the usual abnormalities, a decrease in the N9/iP14 amplitude ratio
      could potentially be used as an electrodiagnostic criterion.

PMID- 24887609
TI  - Efficient and reliable characterization of the corticospinal system using
      transcranial magnetic stimulation.
AB  - PURPOSE: The purpose of this study is to develop a method to reliably
      characterize multiple features of the corticospinal system in a more efficient
      manner than typically done in transcranial magnetic stimulation studies. METHODS:
      Forty transcranial magnetic stimulation pulses of varying intensity were given
      over the first dorsal interosseous motor hot spot in 10 healthy adults. The first
      dorsal interosseous motor-evoked potential size was recorded during rest and
      activation to create recruitment curves. The Boltzmann sigmoidal function was fit
      to the data, and parameters relating to maximal motor-evoked potential size,
      curve slope, and stimulus intensity leading to half-maximal motor-evoked
      potential size were computed from the curve fit. RESULTS: Good to excellent test
      retest reliability was found for all corticospinal parameters at rest and during
      activation with 40 transcranial magnetic stimulation pulses. CONCLUSIONS: Through
      the use of curve fitting, important features of the corticospinal system can be
      determined with fewer stimuli than typically used for the same information.
      Determining the recruitment curve provides a basis to understand the state of the
      corticospinal system and select subject-specific parameters for transcranial
      magnetic stimulation testing quickly and without unnecessary exposure to magnetic
      stimulation. This method can be useful in individuals who have difficulty in
      maintaining stillness, including children and patients with motor disorders.

PMID- 24887610
TI  - Thalamocortical impulse propagation and information transfer in EEG and MEG.
AB  - Measures of functional connectivity and information transfer between the thalamus
      and the cortex can provide detailed insight into brain function. Employing
      magnetoencephalography and electrical median nerve stimulation, it has been
      recently proposed that impulse propagation along the thalamocortical fiber tract
      can be described by a single moving dipole source. Other studies, however, using
      electroencephalography observed dipole clustering in the thalamus and the cortex.
      To assess the source of these conflicting results, we simultaneously recorded
      somatosensory evoked potentials and fields in 12 healthy volunteers. Using a
      single dipole model for the time interval of 10 to 30 milliseconds after stimulus
      onset, we found continuous thalamocortical dipole movement in 10 volunteers and
      dipole clustering in the precortical near thalamic and cortical regions in 2
      volunteers. Thus, independent of the recording method, both clustering and
      movement can be observed. The degree of temporal overlap between the precortical
      near thalamic and the cortical activity distinguished the volunteers exhibiting
      clustering and those exhibiting movement. In a subsequent simulation study, we
      could show that both dipole clustering and dipole movement can occur, depending
      on the temporal overlap of the precortical and cortical activities. In
      conclusion, we propose a two-dipole model to better account for precortical and
      cortical activity and information transfer.

PMID- 24887612
TI  - Effect of age and gender on the number of motor units in healthy subjects
      estimated by the multipoint incremental MUNE method.
AB  - PURPOSE: Motor unit number estimation (MUNE) is a tool for estimating the number
      of motor units. The aim was to evaluate the multipoint incremental MUNE method in
      a healthy population, to analyze whether aging, gender, and the dominant hand
      side influence the motor unit number, and to assess reproducibility of MUNE with
      the Shefner modification. MATERIALS AND METHODS: We studied 60 volunteers (mean
      age, 47 +/- 17.7 years) in four groups aged 18 to 30, 31 to 45, 46 to 60, and
      above 60 years. Motor unit number estimation was calculated in the abductor
      pollicis brevis (APB) and the abductor digiti minimi (ADM) by dividing the single
      motor unit action potential amplitude into the maximal compound motor action
      potential amplitude. RESULTS: Test-retest variability was 7%. The mean value of
      MUNE for APB was 133.2 +/- 43 and for ADM was 157.1 +/- 39.4. Significant
      differences in MUNE results were found between groups aged 18 to 30 and 60 years
      or older and between groups aged 31 to 45 and 60 years or older. Motor unit
      number estimation results correlated negatively with the age of subjects for both
      APB and ADM. Single motor unit action potential, reflecting the size of motor
      unit, increased with the age of subjects only in APB. Compound motor action
      potential amplitude correlated negatively with the age of subjects in APB and
      ADM. Significant correlations were seen between MUNE in APB or ADM and compound
      motor action potential amplitude in these muscles and the age of female subjects.
      A similar relationship was not found in males. CONCLUSIONS: Multipoint
      incremental MUNE method with the Shefner modification is a noninvasive, easy to
      perform method with high reproducibility. The loss of motor neurons because of
      aging could be confirmed by our MUNE study and seems to be more pronounced in
      females.

PMID- 24887613
TI  - SPECT-negative SIRPIDs: less aggressive neurointensive care?
AB  - INTRODUCTION: The management of EEG patterns in comatose intensive care unit
      patients remains poorly studied regarding whether aggressive management improves
      outcomes. We hypothesized that stimulus-induced rhythmic, periodic, or ictal
      discharges (SIRPIDs) could be classified as ictal and interictal using single
      photon emission computerized tomographic (SPECT) imaging to help guide aggressive
      or deescalate anticonvulsant management. METHODS: We performed a retrospective
      review of all cases of ICU patients at a single center, tertiary care academic
      center for evidence of SIRPIDs with concomitant SPECT imaging over a one year
      period. RESULTS: From 2011 to 2012, we retrospectively identified 2 of 235
      intensive care unit EEGs-completed patients (both 20 minutes and continuous EEG),
      who had SIRPIDs who subsequently underwent SPECT imaging. Both patients were
      female, one aged 63 years who had aneurysmal subarachnoid hemorrhage and large
      intraparenchymal hematoma and the other aged 67 years who sustained a cardiac
      arrest. Continuous EEG in both demonstrated stimulation-provoked SIRPIDs within 6
      to 8 days of hospitalization. A SPECT scan using technetium
      hexamethylporpyleneamineoxime (HMPAO) performed during stimulation induced
      SIRPIDs on EEG, followed by a SPECT scan without SIRPIDs on EEG. In both
      patients, regional cerebral hyperperfusion was not present between the two SPECT
      scans. The absence of hyperperfusion on either scan and subtracted SPECT imaging
      helped reduce aggressive anticonvulsant use, infusion of propofol, or additional
      antiepileptic drugs. CONCLUSIONS: Single-photon emission computerized tomographic
      scan-negative SIRPIDs may supplement the EEG and modify aggressive therapies, but
      larger outcome-based studies are needed.

PMID- 24887611
TI  - Age-related decline in bottom-up processing and selective attention in the very
      old.
AB  - Previous research demonstrating age-related deficits in selective attention have
      not included old-old adults, an increasingly important group to study. The
      current investigation compared event-related potentials in 15 young-old (65-79
      years old) and 23 old-old (80-99 years old) subjects during a color-selective
      attention task. Subjects responded to target letters in a specified color
      (Attend) while ignoring letters in a different color (Ignore) under both low and
      high loads. There were no group differences in visual acuity, accuracy, reaction
      time, or latency of early event-related potential components. The old-old group
      showed a disruption in bottom-up processing, indexed by a substantially
      diminished posterior N1 (smaller amplitude). They also demonstrated markedly
      decreased modulation of bottom-up processing based on selected visual features,
      indexed by the posterior selection negativity (SN), with similar attenuation
      under both loads. In contrast, there were no group differences in frontally
      mediated attentional selection, measured by the anterior selection positivity
      (SP). There was a robust inverse relationship between the size of the SN and SP
      (the smaller the SN, the larger the SP), which may represent an anteriorly
      supported compensatory mechanism. In the absence of a decline in top-down
      modulation indexed by the SP, the diminished SN may reflect age-related
      degradation of early bottom-up visual processing in old-old adults.

PMID- 24887614
TI  - Seven-fold increase in viral meningo-encephalitis reports in England and Wales
      during 2004-2013.
AB  - OBJECTIVES: In highly immunised populations viruses contribute to a substantially
      higher proportion of meningo-encephalitis cases. This national study aimed to
      describe population trends in laboratory-confirmed, viral meningo-encephalitis
      reports in England and Wales over a ten-year period. METHODS: Laboratory
      confirmed, viral meningo-encephalitis cases submitted by National Health Service
      hospitals in England and Wales during 2004-13 were analysed. RESULTS: There were
      9941 laboratory-confirmed reports of viral meningo-encephalitis in England and
      Wales over the 10-year period. Number of reports increased across all age-groups
      and for all viruses from 311 (incidence, 0.6/100,000) in 2004 to 2168 in 2013
      (incidence, 3.9/100,000). Median age at diagnosis was 30.6 (IQR, 1.3-51.5) years,
      with a third of cases diagnosed in children. In 2013, infants aged <3 months
      accounted for 27% (588/2168) of cases, but had the highest incidence
      (329/100,000). Enteroviruses were responsible for 52% (5133/9941) of all cases
      and 92% (1952/2121) in <3 month-olds (incidence, 313/100,000 in 2013, equivalent
      to 77/100,000 live-births) followed by herpes simplex (2885/9941; 29%) and
      varicella zoster (1342/9941; 13%), mainly among >=45 year-olds. CONCLUSION:
      Increasing use of molecular testing has led to a 7-fold increase in laboratory
      confirmed, viral meningo-encephalitis reports. Large clinical-observational
      studies are necessary to determine the burden of viral meningo-encephalitis,
      especially in infants.

PMID- 24887615
TI  - The patient-centered medical home, electronic health records, and quality of
      care.
AB  - BACKGROUND: The patient-centered medical home (PCMH) model of primary care is
      being implemented widely, although its effects on quality are unclear. The PCMH
      typically involves electronic health records (EHRs), organizational practice
      change, and payment reform. OBJECTIVE: To compare quality of care provided by
      physicians in PCMHs with that provided by physicians using paper medical records
      and, separately, with that provided by physicians using EHRs without the PCMH (to
      determine whether effects were driven by EHRs). DESIGN: Prospective cohort study
      (2008 to 2010). (ClinicalTrials.gov: NCT00793065). SETTING: The Hudson Valley, a
      7-county, multipayer, multiprovider region in New York. PARTICIPANTS: 675 primary
      care physicians in 312 practices and 143,489 patients. MEASUREMENTS: Claims for
      10 quality measures from the Healthcare Effectiveness Data and Information Set
      were used. Differences in quality were determined using generalized estimating
      equations adjusted for 8 physician characteristics and 4 patient characteristics.
      RESULTS: The PCMH group improved significantly more over time than either the
      paper group or the EHR group for 4 of the 10 measures (by 1 to 9 percentage
      points per measure): eye examinations and hemoglobin A1c testing for patients
      with diabetes, chlamydia screening, and colorectal cancer screening (adjusted P <
      0.05 for each). The odds of overall quality improvement in the PCMH group were 7%
      higher than in the paper group and 6% higher than in the EHR group (adjusted P <
      0.01 for each). LIMITATION: This study was observational, and the possibility of
      unmeasured confounders cannot be excluded. CONCLUSION: The PCMH was associated
      with modest quality improvement. The aspects of the PCMH that drive improvement
      are distinct from but may be enabled by the EHR. PRIMARY FUNDING SOURCE: The
      Commonwealth Fund and the New York State Department of Health.

PMID- 24887616
TI  - Should colorectal cancer screening be considered in elderly persons without
      previous screening? A cost-effectiveness analysis.
AB  - BACKGROUND: The U.S. Preventive Services Task Force recommends against routine
      screening for colorectal cancer (CRC) in adequately screened persons older than
      75 years but does not address the appropriateness of screening in elderly persons
      without previous screening. OBJECTIVE: To determine at what ages CRC screening
      should be considered in unscreened elderly persons and to determine which test is
      indicated at each age. DESIGN: Microsimulation modeling study. DATA SOURCES:
      Observational and experimental studies. TARGET POPULATION: Unscreened persons
      aged 76 to 90 years with no, moderate, and severe comorbid conditions. TIME
      HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: One-time colonoscopy,
      sigmoidoscopy, or fecal immunochemical test (FIT) screening. OUTCOME MEASURES:
      Quality-adjusted life-years gained, costs, and costs per quality-adjusted life
      year gained. RESULTS OF BASE-CASE ANALYSIS: In unscreened elderly persons with no
      comorbid conditions, CRC screening was cost-effective up to age 86 years.
      Screening with colonoscopy was indicated up to age 83 years, sigmoidoscopy was
      indicated at age 84 years, and FIT was indicated at ages 85 and 86 years. In
      unscreened persons with moderate comorbid conditions, screening was cost
      effective up to age 83 years (colonoscopy indicated up to age 80 years,
      sigmoidoscopy at age 81 years, and FIT at ages 82 and 83 years). In unscreened
      persons with severe comorbid conditions, screening was cost-effective up to age
      80 years (colonoscopy indicated up to age 77 years, sigmoidoscopy at age 78
      years, and FIT at ages 79 and 80 years). RESULTS OF SENSITIVITY ANALYSES: Results
      were most sensitive to assuming a lower willingness to pay per quality-adjusted
      life-year gained. LIMITATION: Only persons at average risk for CRC were
      considered. CONCLUSION: In unscreened elderly persons CRC screening should be
      considered well beyond age 75 years. A colonoscopy is indicated at most ages.
      PRIMARY FUNDING SOURCE: National Cancer Institute.

PMID- 24887617
TI  - Rate- and rhythm-control therapies in patients with atrial fibrillation: a
      systematic review.
AB  - BACKGROUND: The comparative effectiveness of treatments for atrial fibrillation
      (AF) is uncertain. PURPOSE: To evaluate the comparative effectiveness of rate-
      and rhythm-control therapies. DATA SOURCES: English-language studies in PubMed,
      EMBASE, and the Cochrane Database of Systematic Reviews between January 2000 and
      November 2013. STUDY SELECTION: Two reviewers independently screened citations to
      identify comparative studies that assessed rate- or rhythm-control therapies in
      patients with AF. DATA EXTRACTION: Reviewers extracted data on study design,
      participant characteristics, interventions, outcomes, applicability, and quality.
      DATA SYNTHESIS: 200 articles (162 studies) involving 28,836 patients were
      included. When pharmacologic rate- and rhythm-control strategies were compared,
      strength of evidence (SOE) was moderate supporting comparable efficacy with
      regard to all-cause mortality (odds ratio [OR], 1.34 [95% CI, 0.89 to 2.02]),
      cardiac mortality (OR, 0.96 [CI, 0.77 to 1.20]), and stroke (OR, 0.99 [CI, 0.76
      to 1.30]) in older patients with mild AF symptoms. Few studies compared rate
      control therapies and included outcomes of interest, which limited conclusions.
      For the effect of rhythm-control therapies in reducing AF recurrence, SOE was
      high favoring pulmonary vein isolation versus antiarrhythmic medications (OR,
      5.87 [CI, 3.18 to 10.85]) and the surgical maze procedure (including pulmonary
      vein isolation) done during other cardiac surgery versus other cardiac surgery
      alone (OR, 7.94 [CI, 3.63 to 17.36]). LIMITATION: Studies were heterogeneous in
      interventions, populations, settings, and outcomes. CONCLUSION: Pharmacologic
      rate- and rhythm-control strategies have comparable efficacy across outcomes in
      primarily older patients with mild AF symptoms. Pulmonary vein isolation is
      better than antiarrhythmic medications at reducing recurrences of AF in younger
      patients with paroxysmal AF and mild structural heart disease. Future research
      should address uncertainties related to subgroups of interest and the effect of
      different therapies on long-term clinical outcomes. PRIMARY FUNDING SOURCE:
      Agency for Healthcare Research and Quality.

PMID- 24887618
TI  - Is there value in medical home implementation beyond the electronic health
      record?

PMID- 24887619
TI  - A "green banana" worth buying in older age: colorectal cancer screening for
      persons older than 75 years without previous screening.

PMID- 24887620
TI  - Of leaves, trees, forests, and primary care.

PMID- 24887621
TI  - Enough is enough.

PMID- 24887622
TI  - Enough is enough.

PMID- 24887623
TI  - Enough is enough.

PMID- 24887624
TI  - Enough is enough.

PMID- 24887625
TI  - Enough is enough.

PMID- 24887627
TI  - Insurance status and the transfer of hospitalized patients.

PMID- 24887626
TI  - Enough is enough.

PMID- 24887628
TI  - Tanning beds and hypervitaminosis D: a case report.

PMID- 24887633
TI  - Development of a pharmacokinetic model of mitotane: toward personalized dosing in
      adrenocortical carcinoma.
AB  - BACKGROUND: Mitotane is the drug of choice in medical treatment of adrenocortical
      carcinoma. The antineoplastic effect seems to be correlated with a minimum plasma
      level of 14 mg/L, but plasma concentration build-up is in general slow due to the
      long elimination half-life. Consequently, the therapeutic effect sets in after
      weeks or even months. The objective of this study was to develop a
      pharmacokinetic model that enables clinicians to adjust dosing based on a target
      drug exposure, which facilitates personalized therapy. METHODS: Data on dosing
      and plasma level measurements performed throughout mitotane therapy were
      retrospectively collected in a population of 29 patients from 2 hospitals. A
      population pharmacokinetic model was constructed based on data from 20 patients
      using iterative 2-stage Bayesian fitting (MWPharm). The model was validated in an
      independent sample of 9 patients. RESULTS: The concentration-time data were best
      described by a 3-compartment model. The model estimated mitotane clearance at
      0.94 +/- 0.37 L/h and a volume of distribution in the steady state at 161 +/- 68
      L/kg of lean body mass. The mean prediction error was 14% +/- 13%. CONCLUSIONS: A
      pharmacokinetic model was developed, which characterized mitotane by slow
      clearance and large volume of distribution. The model seems to be able to predict
      mitotane levels in individual patients with an error margin of 14%. The model
      enables one to adapt dosing based on individual plasma level measurements in
      prospective setting, which improves the accuracy of the prediction. We expect
      that individualization of mitotane dosing leads to anticipated and more rapid
      attainment of the therapeutic levels and potentially to improved clinical
      management of mitotane treatment.

PMID- 24887634
TI  - Effect of proton pump inhibitors on the serum concentrations of the selective
      serotonin reuptake inhibitors citalopram, escitalopram, and sertraline.
AB  - BACKGROUND: The selective serotonin reuptake inhibitors (SSRIs) citalopram,
      escitalopram, and sertraline are all metabolized by the cytochrome P-450
      isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs)
      omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present
      study was to evaluate the effect of these PPIs on the serum concentrations of
      citalopram, escitalopram, and sertraline. METHODS: Serum concentrations from
      patients treated with citalopram, escitalopram, or sertraline were obtained from
      a routine therapeutic drug monitoring database, and samples from subjects
      concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations
      were calculated to compare data from those treated and those not treated with
      PPIs. RESULTS: Citalopram concentrations were significantly higher in patients
      treated with omeprazole (+35.3%; P < 0.001), esomeprazole (+32.8%; P < 0.001),
      and lansoprazole (+14.7%; P = 0.043). Escitalopram concentrations were
      significantly higher in patients treated with omeprazole (+93.9%; P < 0.001),
      esomeprazole (+81.8%; P < 0.001), lansoprazole (+20.1%; P = 0.008), and
      pantoprazole (+21.6%; P = 0.002). Sertraline concentrations were significantly
      higher in patients treated with esomeprazole (+38.5%; P = 0.0014). CONCLUSIONS:
      The effect of comedication with PPIs on the serum concentration of SSRIs is more
      pronounced for omeprazole and esomeprazole than for lansoprazole and
      pantoprazole, and escitalopram is affected to a greater extent than are
      citalopram and sertraline. When omeprazole or esomeprazole are used in
      combination with escitalopram, a 50% dose reduction of the latter should be
      considered.

PMID- 24887635
TI  - Contribution of genetic variation to transgenerational inheritance of DNA
      methylation.
AB  - BACKGROUND: Despite the important role DNA methylation plays in transcriptional
      regulation, the transgenerational inheritance of DNA methylation is not well
      understood. The genetic heritability of DNA methylation has been estimated using
      twin pairs, although concern has been expressed whether the underlying assumption
      of equal common environmental effects are applicable due to intrauterine
      differences between monozygotic and dizygotic twins. We estimate the heritability
      of DNA methylation on peripheral blood leukocytes using Illumina
      HumanMethylation450 array using a family based sample of 614 people from 117
      families, allowing comparison both within and across generations. RESULTS: The
      correlations from the various available relative pairs indicate that on average
      the similarity in DNA methylation between relatives is predominantly due to
      genetic effects with any common environmental or zygotic effects being limited.
      The average heritability of DNA methylation measured at probes with no known SNPs
      is estimated as 0.187. The ten most heritable methylation probes were
      investigated with a genome-wide association study, all showing highly
      statistically significant cis mQTLs. Further investigation of one of these cis
      mQTL, found in the MHC region of chromosome 6, showed the most significantly
      associated SNP was also associated with over 200 other DNA methylation probes in
      this region and the gene expression level of 9 genes. CONCLUSIONS: The majority
      of transgenerational similarity in DNA methylation is attributable to genetic
      effects, and approximately 20% of individual differences in DNA methylation in
      the population are caused by DNA sequence variation that is not located within
      CpG sites.

PMID- 24887636
TI  - Porphyromonas gingivalis stimulates IL-6 and IL-8 secretion in GMSM-K, HSC-3 and
      H413 oral epithelial cells.
AB  - Infection of oral epithelial cells with periodontopathogenic bacteria results in
      the production of pro-inflammatory cytokines involved in the initiation and
      progression of periodontal disease. The purpose of this study was to examine the
      release of interleukin (IL)-6 and IL-8 by oral epithelial cells after exposure to
      Porphyromonas gingivalis. Non-tumor-derived, immortalized human GMSM-K cells, and
      human oral squamous cell carcinoma, HSC-3 and H413 cells, were co-cultured with
      live and heat-inactivated P. gingivalis 2561 (ATCC 33277) and W83 (ATCC BAA
      308TM). IL-6 and IL-8 were quantified in the culture supernatants after 6 and 24
      h. The basal levels of both cytokines and the responses to P. gingivalis were
      strongly dependent on cell type. GMSM-K cells produced less IL-8 than HSC-3 and
      H413 cells. Live P. gingivalis induced significant IL-6 and IL-8 secretion in
      GMSM-K and HSC-3 cells, and heat-inactivation of bacteria enhanced greatly IL-6
      and IL-8 stimulation in these cells. Uninfected H413 cells produced high levels
      of IL-6 and IL-8, but were not responsive to live P. gingivalis; heat-inactivated
      P. gingivalis up-regulated IL-6 and IL-8 secretion in these cells. Since base
      line secretion of IL-6 and IL-8, and responses to P. gingivalis depend on the
      cell type, conclusions on the responses to P. gingivalis should not be based on
      studies with a single cell type. 

PMID- 24887637
TI  - Antifungal activity and identification of Lactobacilli, isolated from traditional
      dairy product "katak".
AB  - Filamentous moulds are the main spoilage microorganisms, responsible for
      significant economic losses and several healthy risks in human food chain. The
      lactic acid bacteria (LAB), especially lactobacilli could be a natural antagonist
      of these dangerous organisms. In Bulgaria, a very limited data exists on the
      antifungal activity of LAB microbiota of fermented dairy products. In the present
      study, four active strains were isolated from traditional fermented curd/yogurt
      like product "katak", produced in Bulgaria from centuries. The new isolates KR3,
      KR4, KR51 and KR53 were identified by API 50 CH biochemical test and different
      molecular methods (species-specific PCR, RAPD-PCR and 16S rDNA sequence analysis)
      as Lactobacillus brevis. According to our knowledge, this is the first data on
      the molecular characterization of the Lactobacillus microbiota of "katak". A
      broad spectrum of antifungal activity of the four L. brevis KR strains against
      test-cultures representatives of carcinogenic, toxigenic, deteriorative and
      allergenic fungi from the genera Aspergillus, Fusarium, Penicillium and
      Trichoderma was estimated. Strains L. brevis KR3, KR4 and KR51 completely
      suppress the growth of Penicillium claviforme, Aspergillus awamori and
      Aspergillus niger. With regard to Aspergillus flavus and Trichoderma viride, a
      lower and strain-specific inhibitory activity was observed. The antifungal
      activity of our new L. brevis isolates seems to be a promising advantage of these
      four strains, suggesting their potential applications in different food
      technologies as bio-preservative agents against moulds. 

PMID- 24887639
TI  - BDNF: no gain without pain?
AB  - Injury to the adult nervous system promotes the expression and secretion of brain
      derived neurotrophic factor (BDNF). Because it promotes neuronal growth, survival
      and neurogenesis, BDNF may initiate compensatory processes that mitigate the
      deleterious effects of injury, disease or stress. Despite this, BDNF has been
      implicated in several injury-induced maladaptive processes including pain,
      spasticity and convulsive activity. This review will concentrate on the
      predominant role of BDNF in the initiation and maintenance of chronic and/or
      neuropathic pain at the spinal, peripheral and central levels. Within the spinal
      dorsal horn, the pattern of BDNF-induced changes in synaptic transmission across
      five different, identified neuronal phenotypes bears a striking resemblance to
      that produced by chronic constriction injury (CCI) of peripheral nerves. The
      appearance of this "pain footprint" thus reflects multiple sensitizing actions of
      microglial-derived BDNF. These include changes in the chloride equilibrium
      potential, decreased excitatory synaptic drive to inhibitory neurons, complex
      changes in inhibitory (GABA/glycinergic) synaptic transmission, increases in
      excitatory synaptic drive to excitatory neurons and the appearance of oscillatory
      activity. BDNF effects are confined to changes in synaptic transmission as there
      is little change in the passive or active properties of neurons in the
      superficial dorsal horn. Actions of BDNF in the brain stem and periphery also
      contribute to the onset and persistence of chronic pain. In spite of its role in
      compensatory processes that facilitate the recovery of the nervous system from
      injury, the widespread maladaptive actions of BDNF mean that there is literally
      "no gain without pain". 

PMID- 24887640
TI  - Towards aryl C-N bond formation in dynamic thin films.
AB  - C-N bond forming reactions are important in organic chemistry. A thin film
      microfluidic vortex fluidic device (VFD) operating under confined mode affords N
      aryl compounds from 2-chloropyrazine and the corresponding amine, without the
      need for a transition metal catalyst. 

PMID- 24887638
TI  - Under a nonadherent state, bone marrow mesenchymal stem cells can be efficiently
      induced into functional islet-like cell clusters to normalize hyperglycemia in
      mice: a control study.
AB  - INTRODUCTION: Bone marrow mesenchymal stem cells (BMSCs) possess low
      immunogenicity and immunosuppression as an allograft, can differentiate into
      insulin-producing cells (IPCs) by in vitro induction, and may be a valuable cell
      source to regenerate pancreatic islets. However, the very low differentiation
      efficiency of BMSCs towards IPCs under adherent induction has thus far hindered
      the clinical exploitation of these cells. The aim of this study is to explore a
      new way to efficiently induce BMSCs into IPCs and lay the groundwork for their
      clinical exploitation. METHODS: In comparison with adherent induction, BMSCs of
      human first-trimester abortus (hfBMSCs) under a nonadherent state were induced
      towards IPCs in noncoated plastic dishes using a three-stage induction procedure
      developed by the authors. Induction effects were evaluated by statistics of the
      cell clustering rate of induced cells, and ultrastructural observation, dithizone
      staining, quantitative polymerase chain reaction and immunofluorescence assay,
      insulin and c-peptide release under glucose stimulus of cell clusters, as well as
      transplantation test of the cell clusters in diabetic model mice. RESULTS: With
      (6.175 +/- 0.263) * 105 cells in 508.5 +/- 24.5 cell clusters, (3.303 +/- 0.331)
      * 105 single cells and (9.478 +/- 0.208) * 105 total cell count on average, 65.08
      +/- 2.98% hfBMSCs differentiated into pancreatic islet-like cell clusters after
      nonadherent induction. With (3.993 +/- 0.344) * 105 cells in 332.3 +/- 41.6 cell
      clusters, (5.437 +/- 0.434) * 105 single cells and (9.430 +/- 0.340) * 105 total
      cell count on average, 42.37 +/- 3.70% hfBMSCs differentiated into pancreatic
      islet-like cell clusters after adherent induction (P < 0.01, n = 10). The former
      is significantly higher than the latter. Calculated according to the cell
      clustering rate and IPC percentage in the cell clusters, 29.80 +/- 3.95% hfBMSCs
      differentiated into IPCs after nonadherent induction and 18.40 +/- 2.08% hfBMSCs
      differentiated into IPCs after adherent induction (P < 0.01, n = 10), the former
      significantly higher than the latter. The cell clusters expressed a broad gene
      profile related to pancreatic islet cells, released insulin and c-peptide in a
      glucose concentration-dependent manner, and normalized hyperglycemia of
      streptozocin-induced mice for at least 80 days following xenograft. Blood glucose
      of grafted mice rose again after their graft removed. A series of examination of
      the grafts showed that transplanted cells produced human insulin in recipients.
      CONCLUSIONS: Our studies demonstrate that nonadherent induction can greatly
      promote BMSCs to form pancreatic islet-like cell clusters, thereby improving the
      differentiation efficiency of BMSCs towards IPCs.

PMID- 24887641
TI  - Thy1.2 driven expression of transgenic His6-SUMO2 in the brain of mice alters a
      restricted set of genes.
AB  - Protein SUMOylation is a post-translational protein modification with a key
      regulatory role in nerve cell development and function, but its function in
      mammals in vivo has only been studied cursorily. We generated two new transgenic
      mouse lines that express His6-tagged SUMO1 and SUMO2 driven by the Thy1.2
      promoter. The brains of mice of the two lines express transgenic His6-SUMO
      peptides and conjugate them to substrates in vivo but cytoarchitecture and
      synaptic organization of adult transgenic mouse brains are indistinguishable from
      the wild-type situation. We investigated the impact of transgenic SUMO expression
      on gene transcription in the hippocampus by performing genome wide analyses using
      microarrays. Surprisingly, no changes were observed in Thy1.2::His6-SUMO1
      transgenic mice and only a restricted set of genes were upregulated in
      Thy1.2::His6-SUMO2 mice. Among these, Penk1 (Preproenkephalin 1), which encodes
      Met-enkephalin neuropeptides, showed the highest degree of alteration.
      Accordingly, a significant increase in Met-enkephalin peptide levels in the
      hippocampus of Thy1.2::His6-SUMO2 was detected, but the expression levels and
      cellular localization of Met-enkephalin receptors were not changed. Thus,
      transgenic neuronal expression of His6-SUMO1 or His6-SUMO2 only induces very
      minor phenotypical changes in mice.

PMID- 24887642
TI  - The extra-adrenal effects of metyrapone and oxazepam on ongoing cocaine self
      administration.
AB  - Investigation of the role of stress in cocaine addiction has yielded an
      efficacious combination of metyrapone and oxazepam, hypothesized to decrease
      relapse to cocaine use by reducing stress-induced craving. However, recent data
      suggest an extra-adrenal role for metyrapone in mediating stress- and addiction
      related behaviors. The interactions between the physiological stress response and
      cocaine self-administration were characterized in rodents utilizing surgical
      adrenalectomy and pharmacological treatment. Male Wistar rats were trained to
      self-administer cocaine (0.25mg/kg/infusion) and food pellets under a concurrent
      alternating fixed-ratio schedule of reinforcement. Surgical removal of the
      adrenal glands resulted in a significant decrease in plasma corticosterone and a
      consequent increase in ACTH, as expected. However, adrenalectomy did not
      significantly affect ongoing cocaine self-administration. Pretreatment with
      metyrapone, oxazepam and their combinations in intact rats resulted in a
      significant decrease in cocaine-reinforced responses. These same pharmacological
      treatments were still effective in reducing cocaine- and food-reinforced
      responding in adrenalectomized rats. The results of these experiments demonstrate
      that adrenally-derived steroids are not necessary to maintain cocaine-reinforced
      responding in cocaine-experienced rats. These results also demonstrate that
      metyrapone may produce effects outside of the adrenal gland, presumably in the
      central nervous system, to affect cocaine-related behaviors. 

PMID- 24887643
TI  - Early administration of tumor necrosis factor-alpha antagonist promotes survival
      of transplanted neural stem cells and axon myelination after spinal cord injury
      in rats.
AB  - Neural stem cell (NSC) transplantation has been reported to be a leading strategy
      to stimulate neuroplasticity, repair neuronal loss and promote the morphologic
      and functional recovery of spinal cord injury (SCI). However, massive death of
      transplanted NSCs is still a problem, which is considered to be related to a
      series of pro-inflammatory cytokines that induce apoptosis, extensive
      demyelination and axonal destruction. Tumor necrosis factor alpha (TNF-alpha), as
      one of the major inflammation initiators, contributes to secondary neural cell
      death. We previously found that the administration of the TNF-alpha antagonist
      etanercept during the acute phase of SCI can reduce the apoptosis of neurons and
      oligodendrocytes. To investigate whether etanercept can suppress transplanted NSC
      apoptosis and promote NSC survival, axon myelination and functional recovery, we
      tested the combination strategy of the early administration of etanercept and NSC
      transplantation. First we observed that etanercept suppressed the TNF-alpha
      expression and apoptosis of transplanted NSCs by Western blot, TUNEL and
      immunofluorescence staining. The Basso, Beattle and Bresnahan scale and motor
      evoked potential were used to evaluate functional recovery. The results suggest
      significantly better recovery after combination therapy. Further,
      histopathological alterations were evaluated by hematoxylin and eosin staining
      and Nissl staining. These procedures showed that the early administration of
      etanercept improved survival of neurons in the ventral horn, restored neural
      morphology and produced a smaller cavity area. We observed most abundant NF
      positive fibers after the combination treatment, indicating that combination
      therapy retained and promoted neural regeneration. Finally, the early suppression
      of TNF-alpha reduced the occurrence of demyelination, and the combination therapy
      led to more myelinated axons, as shown by electron microscopy. These data suggest
      that this strategy significantly protected transplanted NSCs via the anti
      inflammation and anti-apoptosis effects of etanercept, promoting re-myelination,
      neural regeneration and locomotor function.

PMID- 24887645
TI  - Factors affecting the mechanical behavior of Y-TZP.
AB  - AIM: The aim was to evaluate the influence of sandblasting with various
      propulsion pressures on the phase transformation, flexural strength and Weibull
      modulus of a yttria stabilized tetragonal zirconia polycrystalline ceramic (Y
      TPZ). In addition, the susceptibility of cyclic loading and low-temperature
      degradation under two different conditions (chemical and thermal aging) was
      investigated. MATERIALS AND METHODS: The specimens [105bar-shaped specimens
      (19.3*14.5*1.3mm(3))] were equally divided into seven groups (n=15) according to
      the test protocols. The specimens in control group received no surface treatment
      (Group A). Groups B1, B2 and B3 were airborne-particle abraded with 110MUm Al2O3
      particles at 200kPa, 400kPa and 600kPa (2bar, 4bar and 6bar) pressure,
      respectively. Group C was submitted to mechanical cyclic loading under 200N
      20,000 times sinusoidal loading/unloading at a frequency of 10Hz between 10% and
      100% load in distilled water at 37 degrees C. Group D was submitted to thermal
      degradation in an autoclave at 134 degrees C under additional 200kPa pressure for
      5h. Group E was immersed in 4% acetic acid at 80+/-5 degrees C for 168h as
      chemical degradation testing. Following each treatment protocols, the three-point
      flexure test was used to calculate the flexural strength. Additionally, X-ray
      diffraction analysis was used to estimate the relative amount of monoclinic
      phase. The reliability of strength was assessed through the Weibull distribution.
      Statistical analysis was conducted with one-way ANOVA and Tukey's pairwise
      multiple comparisons. The treated and fractured surfaces were observed with SEM.
      RESULTS: Statistical analysis revealed that there were significant differences
      among the flexural strength results of all tested groups (F=4.510, p<0.05). Group
      B2 demonstrated the highest strength values, whereas Group E showed the lowest
      (625.86+/-123.57; 466.56+/-91.50, respectively). Weibull moduli of all tested
      groups were statistically significant and ranging from 4.3 to 8.3. A greater
      amount of monoclinic phase was determined in the specimens of D, E and B3 groups
      (25.43%, 20.89% and 19.71%, respectively). However, lower amount was observed in
      groups A, B1 and B2 (10.02%, 13.35% and 15.19%, respectively). CONCLUSIONS: The
      present study suggested that flexural strength of zirconia was significantly
      decreased by chemical degradation. In addition, surface conditioning, cyclic
      fatigue and thermal, chemical degradation conditions significantly changed the
      structural reliability of the material's strength.

PMID- 24887644
TI  - Invariance detection in the brain: revealed in a stepwise category induction
      task.
AB  - A critical sub-process of category learning is detecting the invariance between
      categorical members. To examine brain activation associated with invariance
      detection at different steps of category learning, a stepwise category induction
      task was used in the present study. Within each trial, three stimuli were
      displayed sequentially, and participants were asked to learn the target category
      corresponding to the invariance among stimuli. Results revealed that invariance
      detection activated the fronto-parietal network. However, the frontal and
      parietal cortices functioned differently throughout the different steps of
      invariance detection. The left middle frontal gyrus (BA 9) was highly activated
      in both steps of invariance detection, but the posterior parietal regions,
      especially the right superior parietal lobule (BA 7), were more active in the
      final step of invariance detection, reflecting increased attention to the
      completion of category learning and the preparation for a subsequent response.
      Furthermore, a psychophysiological interaction analysis (PPI) revealed increased
      connectivity between the left middle frontal gyrus and the bilateral parietal
      cortex during the final step of invariance detection. Overall, the present
      findings imply the necessary role of the fronto-parietal network in variance
      detection. 

PMID- 24887646
TI  - Reliability and validity of the executive function and occupational routines
      scale (EFORTS).
AB  - Sustainable daily routines during childhood are important both for children and
      their parents. Although their affective completion requires well developed
      executive functions (EF), this issue has not been studied until now. The current
      study examined the reliability and validity of the Executive Functions and
      Occupational Routines Scale - EFORTS (developed in Hebrew) which measures
      children's executive control in their daily routines. Internal consistency and
      construct and convergent validity were examined by applying the EFORTS and the
      Behavior Rating Inventory of Executive Functions/preschool version (BRIEF/P) to
      261 children (129 boys, 132 girls) between the ages 3 and 10 (mean=6.1, SD=1.43).
      The findings indicate that the EFORTS is a reliable and valid tool for examining
      children's executive control in three occupational daily routines, focusing
      specifically on metacognitive manifestations of EF. These findings suggest that
      the EFORTS can be a useful tool to assess children with EF deficits, and may
      serve targeting intervention programs toward the accomplishment of daily
      occupational goals. 

PMID- 24887647
TI  - Analogical mapping across modalities in children with specific language
      impairment (SLI).
AB  - Analogical mapping is a domain-general cognitive process found in language
      development, and more particularly in the abstraction of construction schemas.
      Analogical mapping is considered as the general cognitive process which consists
      in the alignment of two or several sequences in order to detect their common
      relational structure and generalize it to new items. The current study
      investigated analogical mapping across modalities in children with specific
      language impairment (SLI). Nineteen children with SLI and their age-matched peers
      were administered two tasks: a linguistic analogical reasoning task (composed of
      syllables) and a similar non-linguistic analogical reasoning task (composed of
      pictures). In the two tasks, the items presented were divided into two groups:
      items with perceptual cues and items without perceptual cues. Children had to
      complete a sequence sharing the same relational structure as previously presented
      sequences. Results showed an expected group effect with poorer performance for
      children with SLI compared to children with typical language development (TLD).
      Results corroborate hypotheses suggesting that children with SLI have
      difficulties with analogical mapping, which may hinder the abstraction of
      construction schemas. Interestingly, whereas no interaction effect between group
      and modality (linguistic vs. non-linguistic) was revealed, a triple interaction
      Group*Modality*Perceptual support was observed. In the non-linguistic task, the
      performance of children with SLI was the same for items with and without
      perceptual clues, but in the linguistic task they performed more poorly for items
      without perceptual cues compared to items with perceptual cues. The results and
      limits of the study are discussed. 

PMID- 24887648
TI  - Controlled synthesis, photoluminescence, and the quantum cutting mechanism of
      Eu(3+) doped NaYbF4 nanotubes.
AB  - Quantum cutting down-conversion has been the subject of intense research activity
      due to its wide application in optoelectronic devices. However, the energy
      transfer mechanism behind this down-conversion process is not fully understood.
      In this work, monodispersed Eu(3+) doped NaYbF4 nanotubes were synthesized by a
      hydrothermal route. Simultaneous phase transition from cubic to hexagonal and
      size modification are controlled by changing the Eu(3+) doping concentration.
      Excited by 393 nm ultraviolet monochromatic light, Eu(3+) doped NaYbF4 nanotubes
      show quantum cutting down-conversion involving visible and broadband near
      infrared emissions through an energy migration process (5)D2 (Eu(3+)) -> (2)F5/2
      (Yb(3+)) + (2)F5/2 (Yb(3+)). Based on the emission spectra of Eu(3+) ions, an
      improved method is proposed to calculate Judd-Ofelt intensity parameters and
      radiative transition probability. A comprehensive seven-level rate-equation model
      is developed to study the energy transfer mechanism. This work offers a method to
      calculate Judd-Ofelt parameters of opaque powder phosphors and to evaluate the
      population dynamics of excited states. 

PMID- 24887649
TI  - Oxidation-assisted ductility of aluminium nanowires.
AB  - Oxidation can drastically change mechanical properties of nanostructures that
      typically have large surface-to-volume ratios. However, the underlying mechanisms
      describing the effect oxidation has on the mechanical properties of
      nanostructures have yet to be characterized. Here we use reactive molecular
      dynamics and show that the oxidation enhances the aluminium nanowire ductility,
      and the oxide shell exhibits superplastic behaviour. The oxide shell decreases
      the aluminium dislocation nucleation stress by increasing the activation volume
      and the number of nucleation sites. Superplasticity of the amorphous oxide shell
      is due to viscous flow as a result of healing of the broken aluminium-oxygen
      bonds by oxygen diffusion, below a critical strain rate. The interplay between
      the strain rate and oxidation rate is not only essential for designing
      nanodevices in ambient environments, but also controls interface properties in
      large-scale deformation processes. 

PMID- 24887650
TI  - Gluteal compartment syndrome after robotic left adrenalectomy.

PMID- 24887651
TI  - Combined variations of superior mesenteric artery branches.

PMID- 24887652
TI  - Age-specific determinants of the safety of laparoscopic colectomy in elderly
      patients with colorectal cancer.

PMID- 24887653
TI  - Right middle lobe torsion from a Morgagni hernia.

PMID- 24887654
TI  - Splenic injury during colonoscopy: a complication hardly thought hence hardly
      sought.

PMID- 24887655
TI  - Preoperative embolization facilitates the treatment of Wunderlich syndrome.

PMID- 24887656
TI  - Dabigatran therapy: minor trauma injuries are no longer minor.

PMID- 24887657
TI  - Impact of implementation of an acute care surgery service on perceptions of
      patient care and resident education.

PMID- 24887658
TI  - Vascular malformation displaying as intestinal obstruction.

PMID- 24887659
TI  - Robotic thoracic esophageal diverticulectomy.

PMID- 24887661
TI  - Niche reconstructive techniques for complex abdominal wall reconstruction: a
      review.
AB  - Abdominal wall defects resulting from recurrent hernias, trauma, and radiation
      necrosis are difficult and challenging to repair given the high rates of
      recurrence and surgical morbidity. Complex abdominal wall defects often require
      the transposition of autologous material to bridge the fascial gap. We present a
      review of niche reconstructive techniques that have been used in complex
      abdominal wall repair. The specific techniques reviewed include use of delayed
      and tunneled pedicled tensor fascia lata myofascial flap, de-epithelialized flap
      closure, free latissimus dorsi myocutaneous flap with or without innervation, and
      abdominal wall transplant. These niche surgical techniques have great potential
      to reduce recurrence rates when used in the proper setting for complex abdominal
      wall reconstruction. More studies are needed to evaluate the relative use of
      these techniques with the more widely established surgical methods of
      reconstruction. 

PMID- 24887660
TI  - Perioperative morbidity and mortality after noncardiac surgery in young adults
      with congenital or early acquired heart disease: a retrospective cohort analysis
      of the National Surgical Quality Improvement Program database.
AB  - An increasing number of patients with congenital heart disease survive to
      adulthood. Expert opinion suggests that noncardiac surgery is a high-risk event,
      but few data describe perioperative outcomes in this population. Using the
      National Surgical Quality Improvement Program database, we identified a cohort of
      patients aged 18 to 39 years with prior heart surgery who underwent noncardiac
      surgery between 2005 and 2010. A comparison cohort with no prior cardiovascular
      surgery was matched on age, sex, race/ethnicity, operation year, American Society
      of Anesthesiologists physical status, and Current Procedural Terminology code. A
      study cohort consisting of 1191 patients was compared with a cohort of 5127
      patients. Baseline dyspnea, inpatient status at the time of surgery, and a prior
      operation within 30 days were more common in the study cohort. Postoperative
      outcomes were less favorable in the study cohort. Observed rates of death,
      perioperative cardiac arrest, myocardial infarction, stroke, respiratory
      complications, renal failure, sepsis, venous thromboembolism, perioperative
      transfusion, and reoperation were significantly higher in the study cohort (P <
      0.01 for all). Mean postoperative length of stay was greater in the study cohort
      (5.8 vs 3.6 days, P < 0.01). Compared with a matched control cohort, young adult
      patients with a history of prior cardiac surgery experienced significantly
      greater perioperative morbidity and mortality after noncardiac surgery. A history
      of prior cardiac surgery represents a marker of substantial perioperative risk in
      this young population that is not accounted for by the matched variables. These
      results suggest that adult patients with congenital heart disease are at risk for
      adverse outcomes and support the need for further registry-based investigations. 

PMID- 24887662
TI  - Prothrombin complex concentrate use in coagulopathy of lethal brain injuries
      increases organ donation.
AB  - Coagulopathy is a defined barrier for organ donation in patients with lethal
      traumatic brain injuries. The purpose of this study was to document our
      experience with the use of prothrombin complex concentrate (PCC) to facilitate
      organ donation in patients with lethal traumatic brain injuries. We performed a 4
      year retrospective analysis of all patients with devastating gunshot wounds to
      the brain. The data were analyzed for demographics, change in international
      normalized ratio (INR), and subsequent organ donation. The primary end point was
      organ donation. Eighty-eight patients with lethal traumatic brain injury were
      identified from the trauma registry of whom 13 were coagulopathic at the time of
      admission (mean INR 2.2 +/- 0.8). Of these 13 patients, 10 patients received PCC
      in an effort to reverse their coagulopathy. Mean INR before PCC administration
      was 2.01 +/- 0.7 and 1.1 +/- 0.7 after administration (P < 0.006). Correction of
      coagulopathy was attained in 70 per cent (seven of 10) patients. Of these seven
      patients, consent for donation was obtained in six patients and resulted in 19
      solid organs being procured. The cost of PCC per patient was $1022 +/- 544. PCC
      effectively reveres coagulopathy associated with lethal traumatic brain injury
      and enabled patients to proceed to organ donation. Although various methodologies
      exist for the treatment of coagulopathy to facilitate organ donation, PCC
      provides a rapid and cost-effective therapy for reversal of coagulopathy in
      patients with lethal traumatic brain injuries. 

PMID- 24887663
TI  - Open abdomen treatment for septic patients with gastrointestinal fistula: from
      fistula control to definitive closure.
AB  - The use of open abdomen in the management of gastrointestinal fistula complicated
      with severe intra-abdominal infection is uncommon. This study was designed to
      evaluate outcomes of our staged approach for the infected open abdomen. Patients
      who had gastrointestinal fistula and underwent open abdomen treatment were
      retrospectively reviewed. Various materials such as polypropylene mesh and a
      modified sandwich package were used to achieve temporary abdominal closure
      followed by skin grafting when the granulation bed matured. A delayed definitive
      operation was performed for final abdominal closure without implant of prosthetic
      mesh. Between 1999 and 2009, 56 (68.3%) of 82 patients survived through this
      treatment. Among them, 42 patients achieved final abdominal closure. Spontaneous
      fistula closure occurred in 16 patients with secondary fistula recorded in six
      patients. Besides, wound complications occurred in 13 patients with two cases for
      pulmonary infection. Within a 12-month follow-up period after definitive closure,
      no additional fistula was recorded excluding planned ventral hernia repair. Open
      abdomen treatment was effective for gastrointestinal fistula complicated by
      severe intra-abdominal infection. A delayed and deliberate operative strategy
      aiming at fistula excision and fascial closure, with simultaneous abdominal wall
      reconstruction, was required for the infected open abdomen. 

PMID- 24887664
TI  - Comparison of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      with mitomycin or carboplatin for diffuse malignant peritoneal mesothelioma.
AB  - Diffuse malignant peritoneal mesothelioma is a rare, aggressive disease.
      Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
      have improved outcomes where systemic chemotherapy has not succeeded. In this
      study, we compare outcomes of patients treated with mitomycin or carboplatin as
      perfusate. In this retrospective study, 47 procedures (CRS + HIPEC) were
      conducted on 44 patients between March 2003 and August 2010 with either mitomycin
      or carboplatin. chi(2) and Student's t test were used for comparison of
      clinicopathological variables and Kaplan-Meier curves and log rank test were used
      to compare overall survival. Median survival of the mitomycin group was 18 months
      with 1- and 5-year survivals of 72.3 and 27.3 per cent, respectively. Median
      survival of the carboplatin group was not reached and 1- and 5-year survivals
      were 89.7 and 62.5 per cent, respectively (P = 0.014). Mean hospital and
      intensive care unit length of stay was 18.9 and 8.7 days in the mitomycin group
      and 12.5 and 2.3 days in the carboplatin group (P = 0.0069). Mean number of
      packed red blood cell units transfused was higher in the mitomycin group compared
      with the carboplatin group (3.54 vs 0.83, P < 0.05). There was no postoperative
      mortality. HIPEC with carboplatin in diffuse malignant peritoneal mesothelioma is
      associated with improved overall survival and shorter hospital stay compared with
      HIPEC with mitomycin. 

PMID- 24887665
TI  - Margin status impacts survival after pancreaticoduodenectomy but negative margins
      should not be pursued.
AB  - Negative margins are the goal with pancreaticoduodenectomy for pancreatic
      adenocarcinoma. Thereby, margins are assessed intraoperatively with frozen
      section analysis and negative margins are pursued. This study was undertaken to
      determine the impact of margin status with pancreaticoduodenectomy for pancreatic
      adenocarcinoma and the value of extending resections to achieve negative margins.
      The intraoperative frozen section analysis and final margins for 448 patients
      undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were assessed
      and their impact on survival was determined. Median data are presented. Two
      hundred ninety-eight (67%) patients had negative margins (R0), an additional 110
      (25%) patients had microscopically positive and macroscopically negative margins
      (R1), and an additional 40 (9%) patients had initially positive microscopic
      margins, which became negative with further resection (R1 -> R0). R0 resections
      were more likely to have smaller tumors, earlier T grade, earlier N grade, lower
      American Joint Committee on Cancer stage, and less frequent extrapancreatic
      extension (P <= 0.03 for each). Survival was better with R0 resections than R1
      resections (20 vs 12 months, P < 0.001); extending resections to achieve negative
      margins (i.e., R1 -> R0) did not improve survival beyond R1 resections (14 vs 12
      months, P = 0.19). Survival after pancreaticoduodenectomy is disappointing.
      Patients with initial negative margins do best. Positive microscopic margins
      reflect more aggressive tumor-specific factors and lead to abbreviated survival
      even with extended resections to achieve negative margins (i.e., R1 -> R0). With
      an initial positive margin, pursuing negative margins does not improve survival
      and, thereby, negative margins should not be "chased." 

PMID- 24887666
TI  - Laparoscopic versus open end colostomy closure: a single-center experience.
AB  - The aim of this study was to review our experience with laparoscopic end
      colostomy closure. A retrospective review of a prospectively entered database was
      performed. Proportions and continuous variables were compared using the Fisher's
      exact and the Mann-Whitney U tests, respectively. Within the study period, 53
      patients underwent closure of end colostomies. The main reasons for the colonic
      resections were perforated diverticulitis (52.7%) and neoplasms (20.8%). In 28
      patients (53%), laparoscopic closure (LC) was attempted. Demographics did not
      differ between the attempted LC and the primary open closure (OC) group. The
      conversion rate from an LC to an OC was 50 per cent (14 of 28), mostly as a
      result of adhesions (71.4%). Hospital length of stay (HLOS) was significantly
      longer for the OC than with the attempted LC group (15.4 +/- 11.9 days vs 11.3 +/
      8.5 days, P = 0.046). The overall complication rate was not different between
      the completed LC and the OC groups (43 vs 56%, P = 0.634). The majority of
      complications detected (91.1%) were minor and could be treated conservatively.
      The role of laparoscopy to close end colostomies is questionable, because the
      conversion rate is high. However, a shorter HLOS can be expected when laparoscopy
      is successful. To reduce morbidity resulting from prolonged operation times, it
      is crucial to convert early and pre-emptively if hostile adhesions are found. 

PMID- 24887667
TI  - Epidemiology of 577 pediatric firearm fatalities: a 2-year review of the National
      Trauma Data Bank.
AB  - The purpose of this study was to delineate the epidemiology of pediatric firearm
      injuries, including ethno-demographic patterns with impact on years of potential
      life lost (YPLL). A 2-year review of the National Trauma Data Bank (2007 to 2008)
      was conducted. Firearm fatalities in records of patients younger than 18 years
      were identified. Data were analyzed by demographic and injury characteristics and
      YPLL was calculated by ethnicity. A total of 577 deaths were identified in the
      pediatric group. Blacks accounted for 49.7 per cent of the fatalities; Hispanics,
      19.2 per cent; whites, 17.7 per cent, and other ethnicity, 13.4 per cent. Median
      Injury Severity Score was 25 with a median Glasgow Coma Scale score of 3.
      Traumatic brain injury was present in 84.2 per cent of the records. Assault
      accounted for 72.8 per cent, self-inflicted injury 12.7 per cent, and
      unintentional injuries were 8.2 per cent. Most firearm fatalities occurred at
      home (33.6%). By emergency department (ED) disposition, 29.3 per cent died in the
      ED, 32.9 per cent were admitted to the intensive care unit, and 30.0 per cent
      taken to the operating room. Blacks had a total of 17,446 YPLL, Hispanics 6,776
      YPLL, and whites 6,718 YPLL. Pediatric firearm fatalities still remain an
      important public health concern. Inclusive gun control policies focused on
      primary prevention of accidental injuries may be more effective in mitigating its
      impact. 

PMID- 24887668
TI  - Prothrombin complex concentrate accelerates international normalized ratio
      reversal and diminishes the extension of intracranial hemorrhage in geriatric
      trauma patients.
AB  - Warfarin therapy increases the incidence intracranial hemorrhage (ICH),
      especially in the geriatric population. Timely reversal of international
      normalized ratio (INR) is integral in the management of these patients for whom
      fresh frozen plasma (FFP) with vitamin K is the standard of treatment. We
      hypothesized that implementing a protocol that used prothrombin complex
      concentrate (PCC) would reverse INR values more swiftly and decrease the amount
      of FFP administered. In November 2011, a protocol was implemented for
      administering PCC to the geriatric population on warfarin admitted for life
      threatening bleeds. These patients received 25 IU/kg ideal body weight of a three
      factor PCC (Profilnine SD) if their INR was over 1.5 or greater. FFP was given if
      follow-up INR revealed an INR of 1.5 or greater. Retrospectively the data from 29
      patients who received PCC were compared with a historical control group of 34
      patients. Protocol use resulted in a significantly faster INR reversal (PCC:
      151.6 +/- 84.3 minutes vs control: 485.0 +/- 321 minutes; P < 0.001), time to
      achieve an INR less than 1.5 (PCC: 484 +/- 242 minutes vs control: 971 +/- 1208
      minutes; P = 0.036), and less FFP administered (PCC: 1.3 +/- 1.0 vs control:3.3
      +/- 1.5; P < 0.001). PCC patients had a decreased incidence of progression of
      their ICH (PCC: 17.2% vs control: 44.2%; P = 0.031). Rapid reversal of
      coagulopathy in geriatric patients on warfarin is vital to limit the extent of
      ICH. PCC allows a much more rapid reversal than standard treatment with only FFP
      and vitamin K. Adopting such a protocol is associated not only with a more rapid
      reversal and less FFP use, but also less patients went on to extend their head
      bleeds. 

PMID- 24887669
TI  - The use of simulation procedural training to improve self-efficacy, knowledge,
      and skill to perform cricothyroidotomy.
AB  - The pre-eminent requirement for surgical education is that it is effective and
      efficient. We sought to determine if the addition of low-fidelity simulation to
      our standard method of teaching cricothyroidotomy improves Postgraduate Year 1
      residents' self-efficacy, knowledge, and skill to perform cricothyroidotomy. The
      teaching methods were standard education using a lecture and video compared with
      standard education plus low-fidelity simulation instruction and practice on a
      mannequin. The methods were randomly assigned. After the assigned teaching in the
      morning and completion of pre- and posttests of self-efficacy and knowledge, the
      residents were evaluated on performance of cricothyroidotomy during the afternoon
      on euthanized swine. Time to complete the procedure and complications were
      recorded. Nineteen residents participated. Time to complete cricothyroidotomy was
      significantly less (P = 0.047) and performance scores were significantly higher
      (P = 0.01) in the simulation group. This group had four (36.4%) complications and
      the no simulation group had one (12.5%) complication (P = 0.34). Both groups
      improved on self-efficacy from pre- to posteducation (P < 0.05). Low-fidelity
      simulation can improve time and skill to perform cricothyroidotomy. 

PMID- 24887670
TI  - Short bowel syndrome after laparoscopic procedures.
AB  - Short bowel syndrome (SBS) is a potential postoperative complication after intra
      abdominal procedures. Whether the laparoscopic approach is as likely to result in
      SBS or the causative mechanisms are similar to open procedures is unknown. Our
      aim was to evaluate potential mechanisms of SBS after laparoscopic procedures.
      The records of 175 adult patients developing SBS as a postoperative complication
      were reviewed. One hundred forty-seven patients had open procedures and 28
      laparoscopic. Colectomy (39%), hysterectomy (11%), and appendectomy (11%) were
      the most common open procedures. SBS followed laparoscopic gastric bypass (46%)
      and cholecystectomy (32%) most frequently. The mechanisms of SBS were different:
      adhesive obstruction (57 vs 22%, P < 0.05) was more common in the open group,
      whereas volvulus (18 vs 46%, P < 0.05) was more common after laparoscopy.
      Overall, ischemia (25 vs 32%) was similar but significantly more laparoscopic
      patients had postoperative hypoperfusion (32 vs 67%, P < 0.05). Eleven of the 13
      laparoscopic bariatric procedures had internal hernias and volvulus. Of the nine
      patients undergoing cholecystectomy, four developed ischemia early
      postoperatively presumably secondary to pneumoperitoneum. SBS is an increasingly
      recognized complication of laparoscopic procedures. The mechanisms of intestinal
      injury differ from open procedures with a higher incidence of volvulus and more
      frequent ischemia from hypoperfusion. 

PMID- 24887671
TI  - To TQIP or not to TQIP? That is the question.
AB  - The Trauma Quality Improvement Program (TQIP) reports a feasible mortality
      prediction model. We hypothesize that our institutional characteristics differ
      from TQIP aggregate data, questioning its applicability. We conducted a 2-year
      (2008 to 2009) retrospective analysis of all trauma activations at a Level 1
      trauma center. Data were analyzed using TQIP methodology (three groups: blunt
      single system, blunt multisystem, and penetrating) to develop a mortality
      prediction model using multiple logistic regression. These data were compared
      with TQIP data. Four hundred fifty-seven patients met TQIP inclusion criteria.
      Penetrating and blunt trauma differed significantly at our institution versus
      TQIP aggregates (61.9 vs 7.8%; 38.0 vs 92.2%, P < 0.01). There were more firearm
      mechanisms of injury and less falls compared with TQIP aggregates (28.9 vs 4.2%;
      8.5 vs 34.8%, P < 0.01). All other mechanisms were not significantly different.
      Variables significant in the TQIP model but not found to be predictors of
      mortality included Glasgow Coma Score motor 2 to 5, systolic blood pressure
      greater than 90 mmHg, age, initial pulse rate in the emergency department,
      mechanism of injury, head Abbreviated Injury Score, and abdominal Abbreviated
      Injury Score. External benchmarking of trauma center performance using mortality
      prediction models is important in quality improvement for trauma patient care.
      From our results, TQIP methodology from the pilot study may not be applicable to
      all institutions. 

PMID- 24887672
TI  - The role of C-reactive protein in the prediction of the clinical severity of
      acute diverticulitis.
AB  - The aim of this study is to investigate the value of C-reactive protein (CRP) and
      of other laboratory parameters obtained during the initial evaluation of the
      patient in the prediction of the clinical severity of acute diverticulitis. The
      records of patients treated for acute diverticulitis at the Oulu University
      Hospital from December 2006 to December 2008 were retrospectively reviewed. Mild
      disease was defined when conservative treatment was successful. Severe acute
      diverticulitis was considered when percutaneous drainage of an abscess and/or
      surgery was necessary. From the 182 patients considered for analysis, 158 (87%)
      had mild disease, whereas 24 (13%) had severe. CRP (P = 0.034) and the Hinchey
      classification (P = 0.006) were shown to be independent risk factors for severe
      acute diverticulitis in the logistic regression analysis. The receiver operating
      characteristic curve showed that a CRP cutoff value of 170 mg/L significantly
      discriminated severe from mild diverticulitis (87.5% sensitivity, 91.1%
      specificity, area under the curve 0.942, P < 0.00001). CRP is a useful tool in
      the prediction of the clinical severity of acute diverticulitis. A mild episode
      is very likely in patients with CRP less than 170 mg/L. Those with higher CRP
      values have a greater probability to undergo surgical treatment or at least a
      percutaneous intervention. 

PMID- 24887673
TI  - Equestrian trauma: injury patterns vary among age groups.
AB  - Patients with equestrian injuries were identified in the trauma registry from
      2004 to 2007. We a priori divided patients into three groups: 0 to 18 years, 19
      to 49 years, and 50 years old or older. There were 284 patients identified with
      equestrian-related trauma. Injury Severity Score for the three major age
      categories 0 to 18 years, 19 to 49 years, and 50 years or older, were 3.47, 5.09,
      and 6.27, respectively. The most common body region injured among all patients
      was the head (26.1%). The most common injuries by age group were: 0 to 18 years,
      upper extremity fractures; 19 to 49 year olds, concussions; and 50 years or
      older, rib fractures. Significant differences were observed among the three age
      groups in terms of percent of patients with rib fractures: percent of patients
      with rib fractures was 2, 8, and 22 per cent in age groups 0 to 18, 19 to 49, and
      50 years or older, respectively. We found different patterns of injuries
      associated with equestrian accidents by age. Head injuries were commonly seen
      among participants in equestrian activities and helmet use should be promoted to
      minimize the severity of closed head injuries. Injury patterns also seem to vary
      among the various age groups that ride horses. This information could be used to
      better target injury prevention efforts among these patients. 

PMID- 24887674
TI  - Determining injuries from posterior and flank stab wounds using computed
      tomography tractography.
AB  - Unlike anterior stab wounds (SW), in which local exploration may direct
      management, posterior SW can be challenging to evaluate. Traditional triple
      contrast computed tomography (CT) imaging is cumbersome and technician-dependent.
      The present study examines the role of CT tractography as a strategy to manage
      select patients with back and flank SW. Hemodynamically stable patients with back
      and flank SW were studied. After resuscitation, Betadine- or Visipaque(r)-soaked
      sterile sponges were inserted into each SW for the estimated depth of the wound.
      Patients underwent abdominal helical CT scanning, including intravenous contrast,
      as the sole abdominal imaging study. Images were reviewed by an attending
      radiologist and trauma surgeon. The tractogram was evaluated to determine SW
      trajectory and injury to intra- or retroperitoneal organs, vascular structures,
      the diaphragm, and the urinary tract. Complete patient demographics including
      operative management and injuries were collected. Forty-one patients underwent CT
      tractography. In 11 patients, tractography detected violation of the intra- or
      retroperitoneal cavity leading to operative exploration. Injuries detected
      included: the spleen (two), colon (one), colonic mesentery (one), kidney
      (kidney), diaphragm (kidney), pneumothorax (seven), hemothorax (two), iliac
      artery (one), and traumatic abdominal wall hernia (two). In all patients, none
      had negative CT findings that failed observation. In this series, CT tractography
      is a safe and effective imaging strategy to evaluate posterior torso SW. It is
      unknown whether CT tractography is superior to traditional imaging modalities.
      Other uses for CT tractography may include determining trajectory from missile
      wounds and tangential penetrating injuries. 

PMID- 24887675
TI  - Cadaver laboratory as a useful tool for resident training.

PMID- 24887676
TI  - Spontaneous internal biliary fistulas from gallstones: Mirizzi's syndrome,
      cholecystoenteric fistula, and gallstone ileus.

PMID- 24887677
TI  - Laparoscopic colectomy is an underused procedure for the elective management of
      colovesical fistulas.

PMID- 24887678
TI  - 'When can I ride again?' Recidivism in children with all-terrain vehicle
      injuries.

PMID- 24887679
TI  - Lower extremity salvage complicated by recurrent microvascular thrombosis in a
      patient with congenital factor VII deficiency.

PMID- 24887680
TI  - The use of a computer-based internal education program for pediatric trauma
      centers: a multicenter ATOMAC study.

PMID- 24887682
TI  - Isosorbide dinitrate inhibits mechanical stress-induced cardiac hypertrophy and
      autophagy through downregulation of angiotensin II type 1 receptor.
AB  - Mechanical stress can induce cardiac hypertrophy and autophagy. Recently, it has
      been reported that nitric oxide donors inhibited autophagy in human chondrocytes.
      Therefore, the effect of isosorbide dinitrate (ISDN) on cardiac hypertrophy and
      autophagy induced by mechanical stress was investigated in this study. A 48-hour
      mechanical stretch and a 4-week transverse aortic constriction were performed to
      induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, before the
      assessment of myocardial autophagy using LC3b-II. ISDN was found to significantly
      reduce mechanical stretch-induced LC3b-II upregulation. Furthermore, mechanical
      stress was shown to upregulate angiotensin II (AngII) type 1 (AT1) receptor
      expression in both cultured cardiomyocytes and in mouse hearts, whereas ISDN was
      demonstrated to significantly suppress the upregulation of the AT1 receptor. It
      was concluded that ISDN could inhibit mechanical stress-induced cardiac
      hypertrophy and autophagy through the downregulation of AT1 receptor expression.

PMID- 24887683
TI  - Simvastatin does not diminish the in vivo degeneration of decellularized aortic
      conduits.
AB  - BACKGROUND: All present biological cardiovascular prostheses are prone to
      progressive in vivo degeneration, which can be partially impaired by
      decellularization. The administration of statins may provide an additional
      beneficial effect. We provide the first in vivo data on the effect of statins on
      decellularized cardiovascular implants. METHODS: Wistar rats with aortic valve
      insufficiency (day 14) were fed either with a pro-calcific diet (group C; n =
      17), or the same diet additionally supplemented with simvastatin (group S; n =
      16). Aortic conduits from Sprague-Dawley rats were detergent-decellularized,
      infrarenally implanted (day 0) in all recipients and explanted at day 28 or day
      84. RESULTS: Sonographic competence of the conduit perfusion was 100%, and
      overall survival amounted to 97%. Simvastatin decreased the low-density
      lipoprotein cholesterol serum levels; however, it did not affect the
      calcification of the implants. Histology revealed alpha-smooth muscle actin
      positive intima hyperplasia in both groups. Extensive matrix metalloproteinase
      activity was observed in calcified areas, especially in group S. Quantitative RNA
      analysis resulted in no differences with regard to several markers of calcifying
      degeneration (alkaline phosphatase, osteopontin, osteocalcin, osteoprotegerin,
      bone morphogenetic protein-2, runt-related transcription factor-2) and
      inflammation (tumor necrosis factor alpha, interleukin 1beta, receptor for
      advanced glycation end products, CD39, CD73), but significantly lower levels of
      interleukin-6 in group S. CONCLUSIONS: In a standardized small animal model of
      accelerated cardiovascular calcification, simvastatin failed to diminish the
      calcification of decellularized aortic conduit implants. This finding confirms
      the observations of recent clinical trials. However, further experiments are
      warranted to elucidate the value of partial benefits associated with lower
      circulating lipid and proinflammatory cytokine levels.

PMID- 24887684
TI  - Assessment of efficacy of proarrhythmia biomarkers in isolated rabbit hearts with
      attenuated repolarization reserve.
AB  - Isolated hearts with reduced repolarization reserve would be suitable for
      assessing the proarrhythmic liability of drugs. However, it is not known which
      proarrhythmia biomarkers indicate the increased susceptibility to torsades de
      pointes arrhythmia (TdP) in such experimental setting. Thus, we estimated the
      efficacy of proarrhythmia biomarkers in isolated hearts with attenuated
      repolarization reserve. Langendorff-perfused rabbit hearts were used.
      Repolarization reserve was reduced by concomitant inhibition of the rapid (IKr)
      and slow (IKs) delayed rectifier potassium currents by dofetilide and HMR-1556,
      respectively. Rate corrected QT (QTc) interval and beat-to-beat variability of
      the QT interval measured in sinus rhythm or irrespective of rhythm even during
      arrhythmias (sinus and absolute QT variability, respectively) were tested. QTc
      failed to predict increased proarrhythmic risk. Sinus QT variability indicated
      proarrhythmic liability when low concentration of dofetilide was used. However,
      when arrhythmias compromised sinus variability measurement during coperfusion of
      catecholamines and elevated concentration of dofetilide, only absolute QT
      variability indicated increased proarrhythmic risk. Absolute QT variability
      parameters seem to be the most practical and sensitive biomarkers of
      proarrhythmic liability in rabbit hearts with reduced repolarization reserve.
      Absolute QT variability parameters could serve as surrogates for torsades de
      pointes in drug-safety investigations in isolated rabbit hearts with attenuated
      repolarization reserve.

PMID- 24887685
TI  - Regulator of calcineurin 1-1L protects cardiomyocytes against hypoxia-induced
      apoptosis via mitophagy.
AB  - Mitochondrial dysfunction induced by myocardial ischemia is the primary cause of
      cardiac cell death. Specific removal of damaged mitochondria through mitophagy
      may be beneficial for cardiomyocyte protection against ischemia. Regulator of
      calcineurin 1-1L (Rcan1-1L) has been implicated in mitophagy induction in
      neurons. However, whether or not Rcan1-1L can evoke mitophagy in cardiomyocytes
      during hypoxia remains unknown. This study aims to investigate the effect of
      Rcan1-1L overexpression on cardiomyocytes during hypoxia and the possible
      underlying mechanism. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay showed that Rcan1-1L overexpression
      inhibited cell growth under normoxic conditions, whereas Rcan1-1L overexpression
      significantly reversed the growth inhibition induced by hypoxia. The results of
      terminal deoxynucleotidyl transferase biotin-dUTP nick end-labeling assay showed
      that cell apoptosis induced by hypoxia was markedly reduced by Rcan1-1L
      overexpression. In addition, Rcan1-1L overexpression inhibited the expression of
      the proapoptotic protein Bcl-2-associated death promoter and increased that of
      the antiapoptotic protein Bcl-2. Rcan1-1L overexpression opened the mitochondrial
      permeability transition pore and decreased mitochondrial mass. Meanwhile, the
      release of reactive oxygen species from mitochondria was suppressed by Rcan1-1L.
      Autophagy flow activation represented by mammalian target of rapamycin inhibition
      and microtubule-associated protein light chain 3 (LC3) upregulation was also
      demonstrated. Compared with endoplasmic reticulum and Golgi apparatus protein
      markers, the mitochondrial protein marker translocase of outer mitochondrial
      membranes 20 (TOM20) was downregulated by Rcan1-1L overexpression. Moreover,
      Rcan1-1L increased mitophagy receptor Parkin translocation into mitochondria from
      cytosol. Additionally, the effect of Rcan1-1L on cell growth, cell apoptosis and
      mitochondria mass was blocked by Parkin expression silencing. Overall, these data
      suggest that Rcan1-1L protects cardiomyocytes from hypoxia-induced apoptosis by
      inducing mitophagy partly through Parkin. This study provided novel insights into
      the prevention and treatment of ischemic heart disease.

PMID- 24887686
TI  - Pioglitazone prevents the endothelial dysfunction induced by ischemia and
      reperfusion in healthy subjects.
AB  - BACKGROUND: No study has investigated whether pioglitazone (an agonist of
      peroxisome proliferator-activated receptor gamma) protects against ischemia and
      reperfusion (IR)-induced endothelial dysfunction in humans. METHODS AND RESULTS:
      In the first crossover study, 20 volunteers were randomized to 1 week of
      pioglitazone (30 mg/d, postoperatively) or control (no treatment). In the second
      single-arm study, 15 volunteers received pioglitazone and the cyclooxygenase-2
      inhibitor meloxicam for 1 week. On day 7, endothelium-dependent flow-mediated
      dilation (FMD) of the distal brachial artery was measured before and after IR (15
      minutes of ischemia followed by 15 minutes of reperfusion in the proximal upper
      arm). Pre-IR brachial-artery diameter and FMD were similar across the 2 sessions
      (control, pioglitazone) in protocol 1 and between the 2 protocols. IR
      significantly blunted FMD after no treatment (pre-IR FMD: 10.2% +/- 2.6%; post-IR
      FMD: 3.5% +/- 1.9%, P < 0.01) but not after pioglitazone administration (pre-IR
      FMD: 9.7% +/- 2.5%; post-IR FMD: 8.8% +/- 2.9%, P = 0.11). This protective effect
      was accompanied by an increase in serum levels of the antioxidant enzyme
      extracellular superoxide dismutase and was not affected by concomitant
      administration of the cyclooxygenase-2 inhibitor meloxicam (P = 0.10).
      CONCLUSIONS: In humans, pioglitazone provides potent protection against IR
      induced endothelial dysfunction.

PMID- 24887687
TI  - Effects of glucagon-like peptide-1 in diabetic rat small resistance arteries.
AB  - We investigated the functional effects of glucagon-like peptide-1 [GLP-1(7-36)]
      and GLP-1(9-36) and the mechanism(s) playing a role in the effects of these
      agents in isolated small resistance arteries from control and diabetic rats.
      Cumulative concentrations of GLP-1(7-36) and GLP-1(9-36) produced concentration
      dependent relaxations in endothelium-intact but not endothelium-denuded arteries
      that were significantly decreased in diabetic rats. GLP-1 receptor antagonist
      exendin(9-39) significantly inhibited responses to GLP-1 analogs. Nitric
      oxide/cyclic guanosine monophosphate pathway blockers, but not indomethacin,
      significantly decreased responses to GLP-1(7-36) or GLP-1(9-36) in control and
      diabetic rats. 4-Aminopyridine or glibenclamide incubation did not alter
      relaxations to GLP-1 analogs. GLP-1(7-36)- and GLP-1(9-36)-induced relaxations
      were blunted significantly and to similar extends by charybdotoxin and apamin
      combination in control and diabetic rats. Catalase did not affect, whereas
      superoxide dismutase (SOD) caused a significant increase in relaxations to GLP-1
      analogs only in diabetic rats. We provided evidence about the relaxant effects of
      GLP-1(7-36) and GLP-1(9-36) in resistance arteries that were reduced in diabetic
      rats. Both calcium-activated potassium channels and endothelium played a major
      role in relaxations. Increment in certain reactive oxygen species and/or
      reduction in superoxide dismutase function might play a role in reduced relaxant
      responses of resistance arteries to GLP-1(7-36) and GLP-1(9-36) in diabetic rats.

PMID- 24887689
TI  - MRI in brain and spinal infection.

PMID- 24887690
TI  - Magnetic resonance imaging in fungal infections of the brain.
AB  - An invasive fungal infection is a rare disease that can occur in otherwise
      healthy individuals. Fungi themselves are universal, and they are overall
      harmless organisms that cause at most a self-limiting disease in the general
      population. Immunocompromised individuals, whether iatrogenically, genetically,
      or acquired, present a group who are especially susceptible to a life-threatening
      disease from a normally innocuous pathogen. Fungi are normally inhaled and are
      cleared by pulmonary defense mechanisms in immunocompetent hosts. Invasion begins
      when these mechanisms fail in depressed immunity. Through bypassing of the
      pulmonary immune system, fungi can spread hematogenously. Fungal infections of
      the central nervous system are the most common extrapulmonary manifestation after
      fungal inhalation. Other risk factors of fungemia include prolonged indwelling
      catheters, maxillofacial infections, uncontrolled diabetes mellitus, systemic
      antibiotics, implanted neurosurgical devices, and intravenous drug abuse. Thus,
      other than direct inoculation via surgical complications or open trauma, central
      nervous system fungal infections are almost never primary. 

PMID- 24887691
TI  - Central nervous system tuberculosis.
AB  - Tuberculosis (TB) has shown a resurgence in nonendemic populations in recent
      years and accounts for 8 million deaths annually in the world. Central nervous
      system involvement is one of the most serious forms of this infection, acting as
      a prominent cause of morbidity and mortality in developing countries. The rising
      number of cases in developed countries is mostly attributed to factors such as
      the pandemic of acquired immunodeficiency syndrome and increased migration in a
      globalized world. Mycobacterium TB is responsible for almost all cases of
      tubercular infection in the central nervous system. It can manifest in a variety
      of forms as tuberculous meningitis, tuberculoma, and tubercular abscess. Spinal
      infection may result in spondylitis, arachnoiditis, and/or focal intramedullary
      tuberculomas. Timely diagnosis of central nervous system TB is paramount for the
      early institution of appropriate therapy, because delayed treatment is associated
      with severe morbidity and mortality. It is therefore important that physicians
      and radiologists understand the characteristic patterns, distribution, and
      imaging manifestations of TB in the central nervous system. Magnetic resonance
      imaging is considered the imaging modality of choice for the study of patients
      with suspected TB. Advanced imaging techniques including magnetic resonance
      perfusion and diffusion tensor imaging may be of value in the objective
      assessment of therapy and to guide the physician in the modulation of therapy in
      these patients. 

PMID- 24887693
TI  - Congenital brain infections.
AB  - Pediatric congenital intracranial infections are a group of different and
      important entities that constitute a small percentage of all pediatric
      infections. The causal factors and clinical presentations are different in
      children compared with adults. They require early recognition because delay
      diagnosis and initiation of treatment may have catastrophic consequences. Despite
      improvements in prenatal screening, vaccine safety, and antibiotics, infections
      of the central nervous system remain an important cause of neurological
      disabilities worldwide. This article reviews the most common congenital
      infections and their imaging findings. 

PMID- 24887692
TI  - Noncongenital central nervous system infections in children: radiology review.
AB  - Infections of the central nervous system (CNS) are a very common worldwide health
      problem in childhood with significant morbidity and mortality. In children,
      viruses are the most common cause of CNS infections, followed by bacterial
      etiology, and less frequent due to mycosis and other causes. Noncomplicated
      meningitis is easier to recognize clinically; however, complications of
      meningitis such as abscesses, infarcts, venous thrombosis, or extra-axial
      empyemas are difficult to recognize clinically, and imaging plays a very
      important role on this setting. In addition, it is important to keep in mind that
      infectious process adjacent to the CNS such as mastoiditis can develop by
      contiguity in an infectious process within the CNS. We display the most common
      causes of meningitis and their complications. 

PMID- 24887694
TI  - Magnetic resonance imaging in neurocysticercosis.
AB  - Cysticercosis in one of the most common parasitic infections in the central
      nervous system. The complex and unpredictable nature of the host immune reaction
      against cysticercosis as well as the pleomorphism of your injuries make the
      disease neurocysticercosis interesting and fascinating to study. Imaging studies
      play an important role in the diagnosis of this disease. Advanced imaging
      techniques have improved detection and visualization of scolex cysts
      extraparenchymal spaces. 

PMID- 24887696
TI  - Regulation of sensory motor circuits used in C. elegans male intromission
      behavior.
AB  - Intromission of a male's copulatory organ into his mate's genital orifice is a
      behavioral step that is conserved in most terrestrial mating behaviors. The
      behavior serves to anchor the male to his mate and aids in the transmission of
      the male's gametes into the female. In all animals, the successful execution of
      intromission likely involves coordinated sensory/motor regulation coupled with
      constant self-monitoring. The compact male C. elegans reproductive nervous system
      provides an accessible experimental model for identification and dissection of
      the molecular and cellular circuit components that promote different motor
      outputs required for the transfer of the male's genetic material into the self
      fertilizing hermaphrodite. The C. elegans male tail contains forty-one sex
      specific muscles and 81 sex-specific neurons, which promote different steps of
      mating behavior. In this review, I will outline the functional contributions of
      the male-specific sensory-motor neurons and their postsynaptic muscles that
      control the motions of the male copulatory spicules during the various phases of
      intromission behavior and ejaculation. In addition, I will summarize the roles of
      neurotransmitter receptors and ion channels that regulate the outputs of
      individual circuit components and describe how the intromission circuit uses
      these molecules to regulate reproductive behavior during male aging and
      nutritional deprivation. 

PMID- 24887695
TI  - Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared
      dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude
      mouse model of human pancreatic cancer.
AB  - Labeling of metastatic tumors can aid in their staging and resection of cancer.
      Near infrared (NIR) dyes have been used in the clinic for tumor labeling.
      However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph
      nodes, which hinders detection of metastasis. In order to overcome these
      problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a
      chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene
      glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse
      model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated
      DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude
      mice. Serum samples were collected at various time points in order to determine
      serum concentrations and elimination kinetics. Conjugated PEGylated dyes had
      significantly higher serum dye concentrations than non-PEGylated dyes (p=0.005
      for the 650 dyes and p<0.001 for the 750 dyes). Human pancreatic tumors
      subcutaneously implanted into nude mice were labeled with antibody-dye conjugates
      and serially imaged. Labeling with conjugated PEGylated dyes resulted in
      significantly brighter tumors compared to the non-PEGylated dyes (p<0.001 for the
      650 dyes; p=0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their
      accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced
      selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific
      antibody, suggesting their future clinical use in fluorescence-guided surgery.

PMID- 24887698
TI  - Activation of lysosomal degradative pathway in spinal cord tissues of carbon
      disulfide-treated rats.
AB  - Chronic exposure to carbon disulfide (CS2) can induce polyneuropathy in
      occupational worker and experimental animals, but underlying mechanism for CS2
      neuropathy is currently unknown. In the present study, male Wistar rats were
      randomly divided into three experimental groups and one control group. The rats
      in experimental groups were treated with CS2 by gavage at dosages of 200, 400 and
      600 mg/kg/day respectively, six times per week for 6 weeks. The formation of
      autophagosomes and lysosomes in motor neurons of rat spinal cord was observed by
      transmission electron microscopy, the level of autophagy-related proteins,
      lysosome-associated membrane protein 1 (LAMP-1), and cathepsin B in spinal cord
      tissues was determined by Western blot analysis, and the activity of cathepsin B
      was measured by fluorescence assay. The results demonstrated that the number of
      lysosomes in motor neurons was markedly increased in CS2-treated rats. In the
      meantime, the administration of CS2 significantly increased the level of
      microtubule-associated protein light chain 3-II (LC3-II), Atg1, UVRAG and LAMP-1
      in rat spinal cord. Furthermore, the content and activity of cathepsin B in rat
      spinal cord also showed a significant elevation. Taken together, this study
      suggested that CS2 intoxication was associated with the activation of lysosomal
      degradative machinery, which might play a protective role against CS2-induced
      neuronal damage.

PMID- 24887697
TI  - Lipopolysaccharide differentially affects the osteogenic differentiation of
      periodontal ligament stem cells and bone marrow mesenchymal stem cells through
      Toll-like receptor 4 mediated nuclear factor kappaB pathway.
AB  - INTRODUCTION: Periodontitis is initiated and sustained by bacteria. However, the
      mechanism of bacteria induced periodontitis is still unknown. We hypothesized
      that bacterial components can affect the functions of stem cells in the
      periodontium. In this study, we comparatively investigated the influence of
      Lipopolysaccharide (LPS) on the osteogenesis potential of human periodontal
      ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMMSCs).
      METHODS: Human PDLSCs and BMMSCs were harvested and mineralized nodule formation
      was assessed by alizarin red S staining. Expression level of osteogenic related
      gene was detected by quantitative RT-PCR (qRT-PCR). The expression of Toll-like
      receptor 4 (TLR4) and its downstream signaling pathway were examined by western
      blot. The role of TLR4 and related signaling pathway in LPS impairing the
      osteogenic potential of human PDLSCs and BMMSCs were also studied by alizarin red
      S staining and qRT-PCR. Experimental periodontitis was induced in adult Sprague
      Dawley rats and the alveolar bone loss was measured by micro computed tomography
      analysis. The expression of alkaline phosphatase (ALP) was assessed by
      immunohistochemistry and the number of osteoclasts was shown by Tartrate
      resistant acid phosphatase (TRAP) staining. RESULTS: LPS decreased the osteogenic
      differentiation of human PDLSCs through TLR4 regulated nuclear factor (NF)-kappaB
      pathway, but not for BMMSCs. Blocking TLR4 or NF-kappaB signaling partially
      reversed the decreased osteogenic potential of PDLSCs and prevented the alveolar
      bone loss caused by LPS experimental periodontitis in rats. The ALP expression in
      the periodontal ligament was elevated after treatment with anti-TLR4 antibody or
      pyrrolidinedithiocarbamate, whereas there was no statistical significance among
      groups for the number of osteoclasts. CONCLUSIONS: These data suggest that LPS
      can activate TLR4 regulated NF-kappaB pathway of human PDLSCs, thus decreasing
      their osteogenic potential. Blockage of TLR4 or NF-kappaB pathway might provide a
      new approach for periodontitis treatment.

PMID- 24887699
TI  - Cytotoxic 9,19-cycloartane triterpenes from the aerial parts of Cimicifuga
      yunnanensis.
AB  - Six new 9,19-cycloartane triterpenes (1-6) were isolated from the aerial parts of
      Cimicifuga yunnanensis. The new chemical structures were determined by extensive
      analyses of 1D and 2D NMR spectroscopy. Compounds 1 and 2 are the first 9,19
      cycloartane triterpenes characterized by CH3-18 shifting from C-13 to C-12 in the
      Cimicifuga spp. The evaluation of inhibition activity against human HL-60, SMMC
      7721, A-549, MCF-7, and SW480 cell lines indicated that compounds 1-6 showed
      different levels of cytotoxic activities with IC50 values ranging from 1.2 to
      27.8 MUm.

PMID- 24887700
TI  - Monoterpenoid indole alkaloids from Alstonia rupestris with cytotoxic,
      antibacterial and antifungal activities.
AB  - A chemical investigation of the 80% EtOH extract of the aerial plant of Alstonia
      rupestris afforded four new monoterpenoid indole alkaloids, 6,7-epoxy-8-oxo
      vincadifformine (1), 11-acetyl-6,7-epoxy-8-oxo-vincadifformine (2), 11-hydroxy-14
      chloro-15-hydroxy-vincadifformine (3), and perakine N1,N4-dioxide (4), together
      with two known compounds, 11-hydroxy-6,7-epoxy-8-oxovincadifformine (5) and
      vinorine N1,N4-dioxide (6). Structural elucidation of all the compounds was
      performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS.
      Alkaloids 1, 2 and 5 showed significant cytotoxicities against all the tested
      tumor cell lines of the head and neck squamous cell carcinoma with IC50 value
      less than 20 MUM and antimicrobial activities against two fungi (Alternaria
      alternata and Phytophthora capsici). Alkaloids 4 and 6 exhibited the activity
      against bacterium Staphylococcus aureus.

PMID- 24887701
TI  - Luminescent multi-terpyridine ligands: towards 2D polymer formation in solution.
AB  - The investigated multiterpyridine chromophores form a 2D network upon metal ion
      complexation that causes profound changes to their photophysical properties; the
      experimental results are complemented by modeling of the electronic properties of
      isolated monomers as well as the structure of the polymeric network. 

PMID- 24887702
TI  - Synthesis of chiral dopants based on carbohydrates.
AB  - Chiral dopants based on carbohydrates for nematic liquid crystals were
      synthesized from D-glucose, and their helical twisting power (HTP) values were
      evaluated. The chiral dopants induced helices in the host nematic liquid
      crystals. An acetyl derivative having an ether-type glycosidic linkage between
      carbohydrate and a mesogenic moiety showed the highest HTP value of 10.4 MUm(-1),
      while an acetyl derivative having an anomeric ester-type linkage did not show any
      HTP. It was surprising that this molecule had no HTP despite the presence of
      chirality in the molecule. A relationship between HTP and specific rotation was
      not observed in this study.

PMID- 24887703
TI  - Synthesis of novel 2-deoxy-beta-benzyl-C-glycosides by highly stereo- and
      chemoselective hydrogenation of exo-glycals.
AB  - Novel 2-deoxy-beta-benzyl-C-glycosides were prepared in good yields and excellent
      stereoselectivity by a route involving the Wittig reaction of glycosyl
      phosphonium salts and reduction of exo-glycals as key steps. Hydrogenation of
      benzyl protected enol ethers was performed with Pd/C(en) as an effective
      chemoselective catalyst to afford exclusively beta anomers. 

PMID- 24887704
TI  - Self-assembly behavior of tail-to-tail superstructure formed by mono-6-O-(4
      carbamoylmethoxy-benzoyl)-beta-cyclodextrin in solution and the solid state.
AB  - A novel mono-modified beta-cyclodextrin (beta-CD) consisting of 4
      carbamoylmethoxy-benzoyl unit at the primary side was synthesized and its self
      assembly behavior was determined by X-ray crystallography and NMR spectroscopy.
      The crystal structure shows a 'Yin-Yang'-like packing mode, in which the modified
      beta-CD exhibits a channel superstructure formed by a tail-to-tail dimer as the
      repeating motif with the substituted group embedded within the hydrophobic cavity
      of the facing beta-CD. The geometry of the substituted group is determined by the
      inclusion of the cavity and is further stabilized by two intermolecular hydrogen
      bonds between the carbonyl O atom and phenyl group. Furthermore, NMR ROESY
      investigation indicates that the self-assembly behavior of the substituted group
      within the beta-CD cavity is retained in aqueous solution, and the effective
      binding constant Ka was calculated to be 1330 M(-1) by means of (1)H NMR
      titration according to iterative determination.

PMID- 24887705
TI  - Dense network of O-H?O and C-H?O interactions in the solid state structure of n
      pentyl-2-chloro-2-deoxy-alpha-D-manno-sept 3-uloside.
AB  - Single crystal X-ray structural analysis of a septanoside, namely, n-pentyl-2
      chloro-2-deoxy sept-3-uloside (1) provides many finer details of the molecular
      structure, in addition to its preferred twist-chair conformation, namely,
      (5,6)TC3,4 conformation. Structural analysis reveals a dense network of O-H?O, C
      H?O and van der Waals interactions that stabilize interdigitized, planar bi-layer
      structure of the crystal lattice.

PMID- 24887707
TI  - Revisiting the relationship between nurse staffing and quality of care in nursing
      homes: an instrumental variables approach.
AB  - This paper revisits the relationship between nurse staffing and quality of care
      in nursing homes using an instrumental variables approach. Most prior studies
      rely on cross-sectional evidence, which renders causal inference problematic and
      policy recommendations inappropriate. We exploit legislation changes regarding
      minimum staffing requirements in eight states between 2000 and 2001 as exogenous
      shocks to nurse staffing levels. We find that registered nurse staffing has a
      large and significant impact on quality of care, and that there is no evidence of
      a significant association between nurse aide staffing and quality of care. A
      comparison of the IV estimation to the OLS estimation of the first-difference
      model suggests that ignoring endogeneity would lead to an underestimation of how
      nurse staffing affects quality of care in nursing homes. 

PMID- 24887706
TI  - Structure and activities of a novel heteroxylan from Cassia obtusifolia seeds and
      its sulfated derivative.
AB  - COB1B1S2 was isolated from an alkaline extract of Cassia obtusifolia seeds, and
      purified by anion-exchange and gel permeation chromatography. It contains
      arabinose, xylose, and glucuronic acid, in the molar ratio of 5:81:14, with an
      apparent molecular weight estimated to be 70.4 kDa. Elucidated by using chemical
      and spectroscopic methods, COB1B1S2 was shown to have a backbone consisting of
      1,4-linked beta-D-Xylp, with one single-unit terminal alpha-D-GlcpA or alpha-L
      Araf substituted at O-2 for nearly every five 1,4-linked Xylp. COB1B1S2 is
      structurally different from typical glucuronoxylans by its absence of methylation
      at O-4 of GlcA. The native COB1B1S2 showed no significant inhibition on the tube
      formation of human microvascular endothelial cells (HMEC) and on the growth of
      liver and colon cancer cells. On the contrary, COB1B1S2-Sul, prepared as the
      sulfated derivative of COB1B1S2, exhibited a significant inhibition on tube
      formation of HMEC in a dose-dependent manner, and on the growth of Bel7402 liver
      cancer cells. These results indicated that the introduction of sulfate groups
      significantly enhanced the biological activity of glucuronoxylan.

PMID- 24887708
TI  - Probing the microenvironment of unimicelles constituted of amphiphilic
      hyperbranched polyethyleneimine using 1-methyl-8-oxyquinolinium betaine.
AB  - In this work, the microenvironment of the core of different unimicelles of
      hyperbranched polyethyleneimine (HPEI) capped with different aliphatic chains
      (stearate, palmitate, and laurate) dissolved in toluene has been investigated. To
      achieve this goal we have used 1-methyl-8-oxyquinolinium betaine (QB) as a
      molecular probe due to its solvatochromic behavior to monitor the micropolarity
      and hydrogen bond donor ability of the unimicelle cores. QB shows that the
      micropolarity and the hydrogen bond donor capability of the polar core of reverse
      unimicellar media are very different than toluene and similar to the one obtained
      with traditional surfactants that form reverse micellar media but at a very low
      unimicelle concentration. Particularly, our results show that the hydrogen
      bonding ability of the core is the driving force for QB to partition toward the
      unimicellar media. 

PMID- 24887709
TI  - An unusual cause of small bowel obstruction secondary to a perforated giant
      jejunal diverticulum.

PMID- 24887710
TI  - Extragastrointestinal stromal tumor localized in the retroperitoneum.

PMID- 24887711
TI  - Silent gastroduodenal perforations resulting from ingested chicken bone:
      presentation of two cases.

PMID- 24887688
TI  - The purinergic neurotransmitter revisited: a single substance or multiple
      players?
AB  - The past half century has witnessed tremendous advances in our understanding of
      extracellular purinergic signaling pathways. Purinergic neurotransmission, in
      particular, has emerged as a key contributor in the efficient control mechanisms
      in the nervous system. The identity of the purine neurotransmitter, however,
      remains controversial. Identifying it is difficult because purines are present in
      all cell types, have a large variety of cell sources, and are released via
      numerous pathways. Moreover, studies on purinergic neurotransmission have relied
      heavily on indirect measurements of integrated postjunctional responses that do
      not provide direct information for neurotransmitter identity. This paper
      discusses experimental support for adenosine 5'-triphosphate (ATP) as a
      neurotransmitter and recent evidence for possible contribution of other purines,
      in addition to or instead of ATP, in chemical neurotransmission in the
      peripheral, enteric and central nervous systems. Sites of release and action of
      purines in model systems such as vas deferens, blood vessels, urinary bladder and
      chromaffin cells are discussed. This is preceded by a brief discussion of studies
      demonstrating storage of purines in synaptic vesicles. We examine recent evidence
      for cell type targets (e.g., smooth muscle cells, interstitial cells, neurons and
      glia) for purine neurotransmitters in different systems. This is followed by
      brief discussion of mechanisms of terminating the action of purine
      neurotransmitters, including extracellular nucleotide hydrolysis and possible
      salvage and reuptake in the cell. The significance of direct neurotransmitter
      release measurements is highlighted. Possibilities for involvement of multiple
      purines (e.g., ATP, ADP, NAD(+), ADP-ribose, adenosine, and diadenosine
      polyphosphates) in neurotransmission are considered throughout. 

PMID- 24887712
TI  - Payer status influence on presenting stage of breast cancer at a community
      teaching hospital cancer program.

PMID- 24887713
TI  - Management of disconnected left pancreatic remnant after necrotizing
      pancreatitis.

PMID- 24887714
TI  - A novel vacuum-assisted excision for giant breast fibroadenomas.

PMID- 24887715
TI  - Gender differences in blood transfusions after trauma related to ages and
      mechanisms.

PMID- 24887716
TI  - Giant abdominal mass: a unique form of metastatic malignant phyllodes tumor of
      the breast.

PMID- 24887717
TI  - Survival with near total small intestinal loss associated with mesenteric vein
      thrombosis: a report of prothrombin G20210A mutation.

PMID- 24887718
TI  - Fournier's gangrene after urethral rupture: an uncommon complication of a common
      procedure.

PMID- 24887719
TI  - Department of Surgery/College of Medicine University of South Alabama: historical
      and contemporaneous perspectives.
AB  - Many members of the medical profession in Mobile, Alabama, have exemplified a
      strong commitment to the education of their colleagues and successors, a
      tradition (L., traditio, "to hand over") that dates from the early 18th century.
      The Mobile General (city/county) Hospital (1830 to 1970) and its successor, the
      Medical Center, University of South Alabama (1971 to the present), were the
      institutional foci of those endeavors. Because it is individuals who create,
      design, and vitalize institutions, this monograph is an acknowledgment of the
      accomplishments of those who gave that endeavor purpose, direction, and meaning,
      particularly with reference to the evolution of surgical education. Numerous
      clinical and societal forces--cultural, economic, political, and social
      influenced that evolution. This compilation gives attribution to a legacy of
      commitment to health and medical/surgical care, education, and research within
      southern Alabama.

PMID- 24887720
TI  - Roscoe Reid Graham (1890 to 1948): a Canadian pioneer in general surgery.
AB  - Roscoe Reid Graham, a Canadian surgeon trained at the University of Toronto, was
      a true pioneer in the field of general surgery. Although he may be best known for
      his omental patch repair of perforated duodenal ulcers-often referred to as the
      "Graham patch"-he had a number of other significant accomplishments that
      decorated his surgical career. Dr. Graham is credited with being the first
      surgeon to successfully enucleate an insulinoma. He ventured to do an essentially
      brand new operation based solely on his patient's symptoms and physical findings,
      a courageous move that even some of the most talented surgeons would shy away
      from. He also spent a large portion of his career dedicated to the study of
      rectal prolapse, working tirelessly to rid his patients of this awful affliction.
      He was recognized by a number of different surgical associations for his
      operative successes and was awarded membership to those both in Canada and the
      United States. Despite all of these accolades, Dr. Graham remained grounded and
      always fervent in his dedication to the patient and their presenting symptom(s),
      reminding us that to do anything more would be "meddlesome." In an age when
      medical professionals are often all too eager to make unnecessary interventions,
      it is imperative that we look back at our predecessors such as Roscoe Reid
      Graham, for they will continually redirect us toward our one and only obligation:
      the patient. 

PMID- 24887721
TI  - Checklist-styled daily sign-out rounds improve hospital throughput in a major
      trauma center.
AB  - The checklist concept has received much attention as a result of its ability to
      improve patient care by minimizing complications. We hypothesized daily sign-out
      rounds using a checklist, by improving team communication and consistency of
      clinical care, could lead to expedited throughput for patients at a major trauma
      center. A retrospective study examined patients admitted to a mature trauma
      center. Two time periods, PRE (September 2008 to January 2009) and POST
      (September 2009 to January 2010), were selected to match for seasonal variation
      in admission diagnosis. An organ system-based checklist was used during daily
      sign-out for all admitted trauma patients in the POST period. We examined
      discharge status, complications and rates, and intensive care unit (ICU) and
      overall hospital length of stay for differences. There were similar numbers of
      patients (824 PRE vs 798 POST) admitted in these two cohorts. We found no
      statistical differences in the incidence of complications or mortality rate. We
      did discover statistically significant differences in the median ICU days (2 PRE
      vs 1 POST, P = 0.007) as well as median hospital length of stay (2 days,
      interquartile differences Q1 to Q3 PRE [1 to 5] and POST [1 to 4] P = 0.000).
      These trends remained valid even among the severely injured (Injury Severity
      Score 16 or greater) with a hospital length of stay of 5 (PRE) versus 3 days
      (POST; P = 0.021). A simple, organ system-based checklist can be successfully
      adopted for daily sign-out round on a busy, multiprovider trauma service. We were
      able to expedite trauma patient throughput in both ICU and overall hospital stays
      with a trend toward decreasing mortality. This improved throughput may
      potentially translate into a cost saving for the hospital. 

PMID- 24887722
TI  - Time-dependent estimates of recurrence and survival in colon cancer: clinical
      decision support system tool development for adjuvant therapy and oncological
      outcome assessment.
AB  - Unanswered questions remain in determining which high-risk node-negative colon
      cancer (CC) cohorts benefit from adjuvant therapy and how it may differ in an
      equal access population. Machine-learned Bayesian Belief Networks (ml-BBNs)
      accurately estimate outcomes in CC, providing clinicians with Clinical Decision
      Support System (CDSS) tools to facilitate treatment planning. We evaluated ml
      BBNs ability to estimate survival and recurrence in CC. We performed a
      retrospective analysis of registry data of patients with CC to train-test
      crossvalidate ml-BBNs using the Department of Defense Automated Central Tumor
      Registry (January 1993 to December 2004). Cases with events or follow-up that
      passed quality control were stratified into 1-, 2-, 3-, and 5-year survival
      cohorts. ml-BBNs were trained using machine-learning algorithms and k-fold
      crossvalidation and receiver operating characteristic curve analysis used for
      validation. BBNs were comprised of 5301 patients and areas under the curve ranged
      from 0.85 to 0.90. Positive predictive values for recurrence and mortality ranged
      from 78 to 84 per cent and negative predictive values from 74 to 90 per cent by
      survival cohort. In the 12-month model alone, 1,132,462,080 unique rule sets
      allow physicians to predict individual recurrence/mortality estimates. Patients
      with Stage II (N0M0) CC benefit from chemotherapy at different rates. At one
      year, all patients older than 73 years of age with T2-4 tumors and abnormal
      carcinoembryonic antigen levels benefited, whereas at five years, all had
      relative reduction in mortality with the largest benefit amongst elderly, highest
      T-stage patients. ml-BBN can readily predict which high-risk patients benefit
      from adjuvant therapy. CDSS tools yield individualized, clinically relevant
      estimates of outcomes to assist clinicians in treatment planning. 

PMID- 24887723
TI  - Nonocclusive ischemic colitis: analysis of risk factors for severity.
AB  - The purpose of this study was to identify risk factors predictive of severe
      nonocclussive ischemic colitis (IC) requiring operation or resulting in
      mortality. One hundred seventeen patients with nonocclussive IC were identified
      and divided into two groups: those with severe disease (n = 24) and those with
      disease that resolved with supportive care (n = 93). Univariate and multivariate
      logistic regression models were used. The splenic flexure was the most common
      involved segment (57.3%), whereas the right colon was involved in 17.9 per cent
      of patients. Multivariate logistic regression identified three independent risk
      factors for severe disease: leukocytosis greater than 15 * 10(9)/L (odds ratio
      [OR], 5.7; confidence interval [CI], 1.5 to 21), hematocrit less than 35 per cent
      (OR, 4.5; CI, 1.1 to 17), and history of atrial fibrillation (OR, 15; CI, 1.3 to
      190). Right-sided IC and chronic renal insufficiency did not affect severity.
      Special attention should be given to patients with the following risk factors for
      a severe course: atrial fibrillation, elevated white blood cell count, and
      anemia. These factors might enable earlier identification of patients who may
      benefit from early operation. Further prospective studies focusing on subgroups
      of IC (occlusive and nonocclusive) are required. 

PMID- 24887724
TI  - Benign breast diseases and body mass index: is there a correlation?
AB  - Breast cancer is the leading cancer affecting women in America. Body mass index
      (BMI) is a known risk factor for the development of breast cancer. The
      relationship of BMI to benign breast disease is less clear. In addition, certain
      benign pathologies are associated with an increased risk of cancer. We sought to
      measure the incidence of benign pathologies and to correlate these findings with
      BMI and age. All patients undergoing breast biopsy at our center from 2000 to
      2005 were identified (n = 1717). Age, BMI, family history, sex, and diagnosis
      were determined. Patients were grouped into BMI, age, and intervention groups.
      chi(2) (P < 0.05) was used to identify statistical significance. Fibrocystic
      disease and fibroadenoma were seen with a lower incidence for patients older than
      55 years of age, whereas pathologies requiring further surgical intervention were
      seen in higher proportions in patients older than 55 years of age. All
      pathologies were noted to decrease with increasing BMI, except for fibroadenoma,
      which peaked in BMI group 25 to 29.9 kg/m(2). The presence of benign pathologies
      was associated with age as expected. Interestingly, although BMI is associated
      with increased risk of breast cancer, increasing BMI was not associated with
      benign pathologies that are associated with increased risk of breast cancer.
      Further study of this area is warranted. 

PMID- 24887725
TI  - Hair loss in females after sleeve gastrectomy: predictive value of serum zinc and
      iron levels.
AB  - A common complication after bariatric surgery is hair loss, which is related to
      rapid weight reduction, but zinc, iron, and other micronutrient deficiencies can
      also be involved. Little is studied after laparoscopic sleeve gastrectomy (LSG).
      A prospective observational study was performed of 42 morbidly obese females
      undergoing LSG. Incidence of hair loss was monitored. Micronutrients were
      investigated preoperatively and three, six, and 12 months after surgery. Sixteen
      patients (41%) reported hair loss in the postoperative course. A significant
      association was observed between hair loss and zinc levels (P = 0.021) but mean
      zinc levels were within the normal range in patients reporting hair loss. Only
      three patients (7.7%) presented low zinc levels, all of them reporting hair loss.
      There was also a significant association between iron levels and alopecia (P =
      0.017), but mean values of the patients with hair loss were within normal range.
      Only four patients (10.2%) presented low iron levels, all of them presenting hair
      loss. A variable consisting of the addition of zinc + iron showed a significant
      association with hair loss (P = 0.013). A cutoff point was established in 115
      (odds ratio, 4; P = 0.006). All the patients but two reporting hair loss
      presented addition levels under 115. This variable showed sensibility 88 per
      cent, specificity 84 per cent, positive predictive value 79 per cent, and
      negative predictive value 91 per cent to predict hair loss. Hair loss is a
      frequent condition after sleeve gastrectomy. In most cases, iron and zinc levels
      are within the normal range. The variable addition (zinc + iron) is a good
      predictor of hair loss. Patients with addition levels below 115 are fourfold more
      susceptible to present hair loss. In these cases, zinc supplements achieve the
      stop of hair loss in most cases. 

PMID- 24887726
TI  - Vasopressor use during emergency trauma surgery.
AB  - Most evidence suggests early vasopressor use is associated with death after
      trauma, but no previous study has focused on patients requiring emergency
      operative intervention (OR). We test the hypothesis that vasopressors are harmful
      in this population. Records from 746 patients requiring OR from July 2009 to
      March 2013 were retrospectively reviewed and stratified based on vasopressor use
      (epinephrine [EPI], phenylephrine, ephedrine, norepinephrine, dobutamine,
      vasopressin) or no vasopressor use. Vasopressors were administered to 225
      patients (30%) during OR; 59 patients (8%) received multiple vasopressors.
      Patients who received vasopressors were older, more severely injured, had worse
      vital signs, and increased mortality rate (all P < 0.001). EPI was independently
      associated with mortality (odds ratio, 6.88; P = 0.001). If patients who received
      EPI were excluded, there was no difference in mortality between those who
      received vasopressors alone or in combination and those that did not (5 vs 6%, P
      = 0.523), although multiple markers of injury severity were worse. We conclude
      that vasopressor use is relatively common in the most severely injured patients
      requiring OR and is associated with mortality. EPI is most often used for cardiac
      arrest, whereas other vasopressors are used for their vasoconstrictive
      properties. This suggests that, except for EPI, vasopressors during OR are not
      independently associated with mortality. 

PMID- 24887728
TI  - Long-term results of pilonidal sinus disease with modified primary closure: new
      technique on 450 patients.
AB  - Chronic pilonidal disease is a debilitating condition that typically affects
      young adults. Controversy still exists regarding the best surgical technique for
      the treatment of pilonidal disease in terms of minimizing disease recurrence and
      patient discomfort. The present study analyzes the results of excision with our
      modified primary closure. This retrospective study involving consecutive patients
      with pilonidal disease was conducted over a 6-year period. From January 2004 to
      January 2010, 450 consecutive patients with primary pilonidal sinus disease
      received this new surgical treatment. Times for complete healing and return to
      work, the duration of operation and of hospitalization, postoperative pain, time
      to first mobilization, and postoperative complications were recorded. To evaluate
      patient comfort, all patients were asked to complete a questionnaire including
      visual analog scale. The median long-term follow-up was 54 months (range, 24 to
      84 months). Four hundred fifty consecutive patients (96 female, 354 male)
      underwent excision. The median age was 25 years (range, 17 to 43 years). The
      median follow-up period was 54 months (range, 24 to 84 months). Four hundred
      twenty completed questionnaires were returned (87% response rate). The median
      duration of hospital stay was eight hours (range, 7 to 10 hours) No patient
      reported severe postoperative pain. Primary operative success (complete wound
      healing without recurrence) was achieved in 98.2 per cent. Two (0.5%) patients
      had a recurrence. The mean time lost to work/school after modified primary
      closure was eight days. Excision and primary closure with this new technique is
      an effective treatment for chronic pilonidal disease. It is associated with low
      morbidity, early return to work, and excellent cosmetic result and a high degree
      of patient satisfaction in the long-term follow-up. 

PMID- 24887727
TI  - Outcomes of emergent inguinal hernia repair in veteran octogenarians.
AB  - Outcomes from emergent inguinal hernia (IH) repair in veteran octogenarians are
      not well described. We reviewed outcomes for this cohort from 2005 to 2012 at the
      VA North Texas Health Care System. There were 15 emergent (Group I) and 86
      elective (Group II) operations performed in octogenarians. Age and American
      Society of Anesthesiologists status were similar in both groups. The rate of
      minor and major complications was higher in Group I compared with Group II (33
      and 19% vs 22 and 2%, respectively; both Ps < 0.001). Hospital length of stay
      (LOS) and intensive care unit LOS were also longer in Group I compared with Group
      II (6.7 +/- 7.0 and 2.5 +/- 4.4 vs 0.8 +/- 1.9 and 0.12 +/- 0.6 days,
      respectively; both Ps < 0.001). Thirty-day mortality was 13 per cent for Group I
      and 0 per cent for Group II. Despite the high rate of comorbid conditions in our
      group, the risk associated with elective repair of IH was not prohibitive. In
      contrast, we observed that 15 per cent of patients presented with an incarcerated
      hernia during the study period and the mortality rate was 13 per cent in this
      cohort. Factors that might predict incarceration in veteran octogenarians need to
      be further investigated. 

PMID- 24887729
TI  - Noncrosslinked porcine-derived acellular dermal matrix for single-stage complex
      abdominal wall herniorrhaphy after removal of infected synthetic mesh: a
      retrospective review.
AB  - This retrospective case review details the use of noncrosslinked intact porcine
      derived acellular dermal matrix (PADM) for incisional herniorrhaphy in patients
      with infected synthetic mesh. A consecutive series of adult patients underwent
      single-stage ventral herniorrhaphy involving removal of infected synthetic mesh
      and repair with PADM by a single surgeon (2009 to 2011). Comorbidities, repair
      procedures, postoperative complications, and hernia recurrence were noted. Of the
      13 patients (mean age, 60 years; female, n = 8), seven (54%) were obese and six
      (46%) had chronic obstructive pulmonary disease/emphysema. Most synthetic mesh
      infections were polymicrobial (n = 7, 46%) or associated with Staphylococcus
      aureus (n = 4 [31%]). Six patients had undergone two or more previous repairs.
      With single-stage herniorrhaphy using PADM, primary fascial closure was achieved
      in 11 patients; bridged closure was required in two patients. Mean (median)
      duration of hospital stay was 12 (7) days and follow-up was 23 (22) months. There
      was one wound infection (drained surgically, PADM remained in place) and one
      seroma (resolved without intervention) observed during follow-up. There were two
      hernia recurrences, both in patients who received PADM as bridged repair. PADM
      yielded favorable outcomes when used for single-stage repair of complex ventral
      hernias in high-risk patients with infected synthetic mesh. 

PMID- 24887730
TI  - Pediatric appendectomy: optimal surgical timing and risk assessment.
AB  - Appendicitis is one of the most common pediatric surgical problems. In the older
      surgical paradigm, appendectomy was considered to be an emergent procedure;
      however, with changes to resident work hours and other economic factors, the
      operation has evolved into an urgent and deliberately planned intervention. This
      paradigm shift in care has not necessarily seen universal buy-in by all
      stakeholders. Skeptics worry about the higher incidence of complications,
      particularly intra-abdominal abscess (IAA), associated with the delay to
      appendectomy with this strategy. Development of IAA after pediatric appendectomy
      greatly burdens the healthcare system, incapacitates patients, and limits family
      functionality. The risk factors that influence the development of IAA after
      appendectomy were evaluated in 220 children admitted to a large urban teaching
      hospital over a recent 1.5-year period. Preoperative risk factors included in the
      study were age, sex, weight, ethnicity, duration and nature of symptoms, white
      cell count, and ultrasound or computed tomography scan findings (appendicolith,
      peritoneal fluid, abscess, phlegmon), failed nonoperative management, antibiotics
      administered, and timing. Intraoperative factors included were timing of
      appendectomy, surgical and pathological findings of perforation, open or
      laparoscopic procedure, and use of staple or Endoloop to ligate the appendix.
      Postoperative factors included were duration and type of antibiotic therapy.
      There were 94 (43%) perforated and 126 (57%) nonperforated appendicitis during
      the study period. The incidence of postoperative IAA was 4.5 per cent (nine of
      220). Children operated on after overnight antibiotics and resuscitation had a
      significantly lower risk of IAA as compared with children managed by other
      strategies (P < 0.0003). Of the preoperative factors, only the presence of a
      fever in the emergency department (P < 0.001) and identification of complicated
      appendicitis on imaging (P < 0.0001) were significant risk factors for
      postoperative abscess development. Perforated appendicitis carries a higher risk
      of development of IAA that is not reduced by an emergent operative or delayed
      nonoperative management strategy. The timing of appendectomy appears to be an
      extremely important factor in reducing the incidence of IAA after all
      presentations of appendectomy. The role of resuscitation and antibiotics in
      limiting the effects of the inflammatory cascade and development of laboratory
      markers that accurately measure the latter need to be the focus of further
      research in this field. 

PMID- 24887731
TI  - Evaluation of predictive factors in patients with nonalcoholic fatty liver
      disease after pancreaticoduodenectomy.
AB  - Patients who undergo pancreaticoduodenectomy (PD) are at risk of steatosis
      because resection of the pancreatic head causes pancreatic exocrine and endocrine
      insufficiency. We investigated the clinicopathological features and the risk
      factors of nonalcoholic fatty liver disease (NAFLD) after PD. This was a
      retrospective study of 100 patients who underwent PD between April 2007 and
      December 2012 in our institution. Preoperative demographic and clinical data,
      surgical procedures, pathological diagnosis, postoperative course findings, and
      complication details were collected prospectively. The patients were divided into
      the following two groups: Group A consisted of 12 patients who developed
      postoperative NAFLD, and Group B consisted of 88 patients who did not develop
      postoperative NAFLD. Pancreatic carcinoma and pancreatic texture showed similar
      findings. Additionally, we found that blood loss significantly correlated with
      the incidence of nonalcoholic steatohepatitis after PD. In multivariate analysis,
      only blood loss was identified as the most influential risk factor for NAFLD
      (hazard ratio, 1.0001; P = 0.016). Blood loss was identified as an independent
      risk factor for the development of NAFLD after PD. Further prospective studies
      are needed to identify factors that put patients at risk for NAFLD after PD.
      Continuing efforts should be made to improve patient outcomes and understand the
      pathogenesis of postpancreatectomy NASH. 

PMID- 24887733
TI  - Pediatric helmet use in residential areas.

PMID- 24887732
TI  - Lower vitamin D levels in surgical hyperparathyroidism versus thyroid patients.
AB  - Low vitamin D levels have been shown to be associated with primary
      hyperparathyroidism, but it is unclear whether vitamin D deficiency may be an
      etiologic factor in the development of primary hyperparathyroidism. To
      investigate this, we compared preoperative vitamin D levels of patients
      undergoing surgery for primary hyperparathyroidism with those of patients
      undergoing surgery for benign thyroid disease. With Institutional Review Board
      approval, data were collected prospectively on patients undergoing
      parathyroidectomy or thyroidectomy by one surgeon between March 2006 and July
      2011. Patients were excluded if they underwent simultaneous thyroid and
      parathyroid surgery, had secondary or tertiary hyperparathyroidism, if no
      preoperative vitamin D level was measured, or if they took vitamin D supplements.
      Inclusion criteria were met by 219 patients who underwent parathyroidectomy and
      186 patients who underwent thyroid surgery. Patient age, sex, race, and
      preoperative vitamin D levels (vitamin D 25-OH; normal, 32 to 100 pg/mL) were
      collected. Statistical analysis was performed using linear regression. Vitamin D
      levels were significantly lower in the parathyroid group compared with the
      thyroid group (23.8 vs 28.5 pg/mL; P < 0.001). This difference was also observed
      after adjustment for age, sex, and race with a mean difference of 4.87 pg/mL (P <
      0.001). Statistically significant associations between lower vitamin D levels and
      patients younger than 50 years (P = 0.048), male sex (P = 0.03), and nonwhite
      race were identified (P < 0.001). Patients with primary hyperparathyroidism are
      more likely to have lower vitamin D levels than a control surgical population.
      Further study is needed to determine whether low vitamin D levels may be an
      etiologic factor associated with the development of hyperparathyroidism. 

PMID- 24887734
TI  - Surgical approach for totally implantable venous access devices: consideration
      after 753 consecutive procedures.

PMID- 24887735
TI  - Is a routine colonoscopy before esophagectomy necessary?

PMID- 24887736
TI  - What is the appropriate management for perforated gastric cancer?

PMID- 24887737
TI  - Allergic contact dermatitis after repeated exposure to dermabondTM.

PMID- 24887738
TI  - Evaluating informed consent obtained by surgical residents.

PMID- 24887741
TI  - Improved spindle detection through intuitive pre-processing of
      electroencephalogram.
AB  - BACKGROUND: Numerous signal processing techniques have been proposed for
      automated spindle detection on EEG recordings with varying degrees of success.
      While the latest techniques usually introduce computational complexity and/or
      vagueness, the conventional techniques attempted in literature have led to poor
      results. This study presents a spindle detection approach which relies on
      intuitive pre-processing of the EEG prior to spindle detection, thus resulting in
      higher accuracy even with standard techniques. NEW METHOD: The pre-processing
      techniques proposed include applying the derivative operator on the EEG,
      suppressing the background activity using Empirical Mode Decomposition and
      shortlisting candidate EEG segments based on eye-movements on the EOG.
      RESULTS/COMPARISON: Results show that standard signal processing tools such as
      wavelets and Fourier transforms perform much better when coupled with apt pre
      processing techniques. The developed algorithm also relies on data-driven
      thresholds ensuring its adaptability to inter-subject and inter-scorer
      variability. When tested on sample EEG segments scored by multiple experts, the
      algorithm identified spindles with average sensitivities of 96.14 and 92.85% and
      specificities of 87.59 and 84.85% for Fourier transform and wavelets
      respectively. These results are found to be on par with results obtained by other
      recent studies in this area.

PMID- 24887742
TI  - Initial results of finger imaging using photoacoustic computed tomography.
AB  - We present a photoacoustic computed tomography investigation on a healthy human
      finger, to image blood vessels with a focus on vascularity across the
      interphalangeal joints. The cross-sectional images were acquired using an imager
      specifically developed for this purpose. The images show rich detail of the
      digital blood vessels with diameters between 100 MUm and 1.5 mm in various
      orientations and at various depths. Different vascular layers in the skin
      including the subpapillary plexus could also be visualized. Acoustic reflections
      on the finger bone of photoacoustic signals from skin were visible in sequential
      slice images along the finger except at the location of the joint gaps. Not
      unexpectedly, the healthy synovial membrane at the joint gaps was not detected
      due to its small size and normal vascularization. Future research will
      concentrate on studying digits afflicted with rheumatoid arthritis to detect the
      inflamed synovium with its heightened vascularization, whose characteristics are
      potential markers for disease activity.

PMID- 24887743
TI  - Catheter-based photoacoustic endoscope.
AB  - We report a flexible shaft-based mechanical scanning photoacoustic endoscopy
      (PAE) system that can be potentially used for imaging the human gastrointestinal
      tract via the instrument channel of a clinical video endoscope. The development
      of such a catheter endoscope has been an important challenge to realize the
      technique's benefits in clinical settings. We successfully implemented a
      prototype PAE system that has a 3.2-mm diameter and 2.5-m long catheter section.
      As the instrument's flexible shaft and scanning tip are fully encapsulated in a
      plastic catheter, it easily fits within the 3.7-mm diameter instrument channel of
      a clinical video endoscope. Here, we demonstrate the intra-instrument channel
      workability and in vivo animal imaging capability of the PAE system.

PMID- 24887744
TI  - Mapping optical fluence variations in highly scattering media by measuring
      ultrasonically modulated backscattered light.
AB  - Knowledge of the local optical fluence in biological tissue is of fundamental
      importance for biomedical optical techniques to achieve quantification. We report
      a method to noninvasively measure the local optical fluence in optically
      inhomogeneous scattering media. The concept is based on two aspects: the local
      tagging of light using ultrasonic modulation and the photon path reversibility
      principle. Our method has advantages over known computational-based fluence
      mapping techniques, for its purely experimental nature and without the
      requirement of prior knowledge of the optical properties of the medium. We
      provide a theoretical formalism and validation of the method with experiments in
      tissue-like phantoms. Further, we combine our method with photoacoustic imaging
      and compensate the photoacoustic signals for fluence variations in optically
      inhomogeneous media.

PMID- 24887745
TI  - Studies of tropical fruit ripening using three different spectroscopic
      techniques.
AB  - We present a noninvasive method to study fruit ripening. The method is based on
      the combination of reflectance and fluorescence spectroscopies, as well as gas in
      scattering media absorption spectroscopy (GASMAS). Chlorophyll and oxygen are two
      of the most important constituents in the fruit ripening process. Reflectance and
      fluorescence spectroscopies were used to quantify the changes of chlorophyll and
      other chromophores. GASMAS, based on tunable diode laser absorption spectroscopy,
      was used to measure free molecular oxygen in the fruit tissue at 760 nm, based on
      the fact that the free gases have much narrower spectral imprints than those of
      solid materials. The fruit maturation and ripening processes can be followed by
      studying the changes of chlorophyll and oxygen contents with these three
      techniques.

PMID- 24887746
TI  - New eye phantom for ophthalmic surgery.
AB  - In this work, we designed and realized a new phantom able to mimic the principal
      mechanical, rheological, and physical cues of the human eye and that can be used
      as a common benchmark to validate new surgical procedures, innovative
      vitrectomes, and as a training system for surgeons. This phantom, in particular
      its synthetic humor vitreous, had the aim of reproducing diffusion properties of
      the natural eye and can be used as a system to evaluate the pharmacokinetics of
      drugs and optimization of their dose, limiting animal experiments. The eye
      phantom was built layer-by-layer starting from the sclera up to the retina, using
      low cost and easy to process polymers. The validation of the phantom was carried
      out by mechanical characterization of each layer, by diffusion test with
      commercial drugs into a purposely developed apparatus, and finally by a team of
      ophthalmic surgeons. Experiments demonstrated that polycaprolactone,
      polydimethylsiloxane, and gelatin, properly prepared, are the best materials to
      mimic the mechanical properties of sclera, choroid, and retina, respectively. A
      polyvinyl alcohol-gelatin polymeric system is the best for mimicking the
      viscosity of the human humor vitreous, even if the bevacizumab half-life is lower
      than in the human eye.

PMID- 24887750
TI  - Chronic kidney disease and the aging population.

PMID- 24887747
TI  - Efficacy of laser phototherapy in comparison to topical clobetasol for the
      treatment of oral lichen planus: a randomized controlled trial.
AB  - Oral lichen planus (OLP) is a relatively common chronic mucocutaneous
      inflammatory disease and a search for novel therapeutic options has been
      performed. We sought to compare the efficacy of laser phototherapy (LPT) to
      topical clobetasol propionate 0.05% for the treatment of atrophic and erosive
      OLP. Forty-two patients with atrophic/erosive OLP were randomly allocated to two
      groups: clobetasol group (n=21): application of topical clobetasol propionate gel
      (0.05%) three times a day; LPT group (n=21): application of laser irradiation
      using InGaAlP diode laser three times a week. Evaluations were performed once a
      week during treatment (Days 7, 14, 21, and 30) and in four weeks (Day 60) and
      eight weeks (Day 90) after treatment. At the end of treatment (Day 30),
      significant reductions in all variables were found in both groups. The LPT group
      had a higher percentage of complete lesion resolution. At follow-up periods (Days
      60 and 90), the LPT group maintained the clinical pattern seen at Day 30, with no
      recurrence of the lesions, whereas the clobetasol group exhibited worsening for
      all variables analyzed. These findings suggest that the LPT proved more effective
      than topical clobetasol 0.05% for the treatment of OLP.

PMID- 24887751
TI  - Renal paratransplant hernia. An uncommon variant of internal hernia. Are we aware
      of it?

PMID- 24887752
TI  - Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year
      follow-up results.

PMID- 24887753
TI  - Postirradiation cutaneous angiosarcoma mimicking a cyst in a heart transplant
      recipient.

PMID- 24887754
TI  - SPRC protects hypoxia and re-oxygenation injury by improving rat cardiac
      contractile function and intracellular calcium handling.
AB  - S-Propargyl-L-cysteine (SPRC, also named as ZYZ-802) is a new compound
      synthesized in our lab. We investigated whether SPRC has exerted protective
      effects against cardiac hypoxia/re-oxygenation (H/R) and also explored its
      mechanisms. In our study, isolated ventricular myocytes were subject to a
      simulated hypoxia solution for 30 min to induce cell injury. Intracellular
      concentration of Ca(2+) ([Ca(2+)]i) was measured using specific dyes and detected
      by digital imaging apparatus. Apoptotic cells were evaluated by TUNEL assay.
      Intervention with SPRC (10 MUM) 30 min before hypoxia, can significantly
      attenuate the apoptosis of isolated papillary muscles resulting from the H/R
      injury and protect morphology of the muscles. In isolated ventricular myocytes,
      SPRC considerably improved left ventricular functional recovery. SPRC also
      suppressed the increase of ([Ca(2+)]i) during hypoxia stage. By measuring the
      calcium transient of the cell we concluded that SPRC can preserve the RyR and
      SERCA activities and improve Ca(2+) handling during the H/R. Furthermore, the
      protective effect of SPRC can be partly blocked by CSE inhibitor PAG.

PMID- 24887756
TI  - Enhanced photostability of an anthracene-based dye due to supramolecular
      encapsulation: a new type of photostable fluorophore for single-molecule study.
AB  - For single-molecule fluorescence studies, highly photostable fluorophores are
      absolutely imperative, because photo-induced degradation (i.e., photobleaching)
      limits the observation time of individual molecules. Herein, the photophysics and
      photostability of a highly fluorescent 9,10-bis(phenylethynyl)anthracene
      derivative (G) and its self-assembled boronic ester encapsulation complex (G@Cap)
      embedded in a glassy polymer matrix are investigated by single-molecule
      fluorescence spectroscopy (SMFS). The heterogeneity of the fluorescence emission
      wavelength and triplet blinking kinetics of the guest G are significantly
      decreased by supramolecular encapsulation due to conformational restriction and
      reduced heterogeneity in the local environment. A nearly 10-fold increase in the
      photostability of G due to encapsulation is quantitatively confirmed by
      evaluating the photobleaching yields of G and G@Cap. In addition, it is found
      that the G@Cap is >30-fold more photostable than rhodamine 6G, a widely used
      fluorescent dye in single-molecule studies. These results demonstrate that the
      G@Cap can serve as a very bright, long-lasting fluorescent probe for single
      molecule studies. 

PMID- 24887755
TI  - Interaction of protein phosphatase inhibitors with membrane lipids assessed by
      surface plasmon resonance based binding technique.
AB  - The interaction of okadaic acid (OA), tautomycin (TM), microcystin-LR (MC-LR),
      cantharidin (CA), epigallocatechin-gallate (EGCG) and cyclosporin A (CsA),
      inhibitors of protein phosphatases, with liposome covered surfaces prepared from
      the lipid extracts of bovine brain, heart and liver was investigated by surface
      plasmon resonance (SPR) based binding technique. The SPR sensorgrams indicated
      reversible association or partial intercalation of the inhibitors with liposomes
      at 20 degrees C or 37 degrees C, respectively. Distinct lipid composition
      specificities were reflected in different saturation values of inhibitor binding
      in a decreasing order of liver>heart>>brain lipids. Assaying the effect of OA,
      TM, MC-LR, CA and EGCG on the activity of protein phosphatases in neuroblastoma
      B50, cardiomyoblast H9C2 and hepatocarcinoma HepG2 cells implied that the cell
      type specific association of phosphatase inhibitors with membrane lipids may
      influence their inhibitory potencies exerted on intact cells. 

PMID- 24887757
TI  - Why the photocatalytic activity of Mo-doped BiVO4 is enhanced: a comprehensive
      density functional study.
AB  - To explore the origin of the enhanced photocatalytic activity of Mo-doped
      monoclinic BiVO4, variations of the structures and the electronic properties, as
      well as the adsorption behavior of water on the (010) surface, introduced by the
      Mo dopant have been investigated by means of density functional theory
      computations. For the bulk phase, Mo atoms prefer to substitute the V atoms,
      which can effectively accelerate the separation of carriers. For the (010)
      surface, Mo atoms prefer to substitute the Bi atoms at the outermost layer. Mo
      doping on the surface can result in surface oxygen quasi-vacancies and enhance
      the exposure of surface Bi atoms, which is confirmed to improve the adsorption of
      water molecules. Our results demonstrate that the enhanced photocatalytic
      activity of Mo-doped monoclinic BiVO4 is derived from the facilitated separation
      of photoinduced carriers and introduced surface oxygen quasi-vacancies. 

PMID- 24887760
TI  - Clinical decision making in patients with thyroid nodules.

PMID- 24887761
TI  - Coronary artery bypass grafting vs percutaneous coronary intervention in
      multivessel disease.

PMID- 24887762
TI  - Clinical decision making in patients with thyroid nodules--reply.

PMID- 24887763
TI  - Coronary artery bypass grafting vs percutaneous coronary intervention in
      multivessel disease.

PMID- 24887764
TI  - Coronary artery bypass grafting vs percutaneous coronary intervention in
      multivessel disease--reply.

PMID- 24887765
TI  - Did extra resources or the medical home model improve care?

PMID- 24887766
TI  - Did extra resources or the medical home model improve care?--Reply.

PMID- 24887767
TI  - Low-risk chest pain in the emergency department: should we be focusing on better
      follow-up instead of accelerated testing?

PMID- 24887768
TI  - Comments regarding "My thyroid story".

PMID- 24887769
TI  - Response to "Mandatory anesthesia".

PMID- 24887770
TI  - Low-risk chest pain in the emergency department--reply.

PMID- 24887772
TI  - Response to "Mandatory anesthesia"--reply.

PMID- 24887775
TI  - Idiopathic myointimal hyperplasia of the mesenteric veins.

PMID- 24887774
TI  - The Effect of Nutritional Status in the Pathogenesis of Critical Illness Myopathy
      (CIM).
AB  - The muscle wasting and loss of specific force associated with Critical Illness
      Myopathy (CIM) is, at least in part, due to a preferential loss of the molecular
      motor protein myosin. This acquired myopathy is common in critically ill
      immobilized and mechanically ventilated intensive care patients (ICU). There is a
      growing understanding of the mechanisms underlying CIM, but the role of
      nutritional factors triggering this serious complication of modern intensive care
      remains unknown. This study aims at establishing the effect of nutritional status
      in the pathogenesis of CIM. An experimental ICU model was used where animals are
      mechanically ventilated, pharmacologically paralysed post-synaptically and
      extensively monitored for up to 14 days. Due to the complexity of the
      experimental model, the number of animals included is small. After exposure to
      this ICU condition, animals develop a phenotype similar to patients with CIM. The
      results from this study show that the preferential myosin loss, decline in
      specific force and muscle fiber atrophy did not differ between low vs. eucaloric
      animals. In both experimental groups, passive mechanical loading had a sparing
      effect of muscle weight independent on nutritional status. Thus, this study
      confirms the strong impact of the mechanical silencing associated with the ICU
      condition in triggering CIM, overriding any potential effects of caloric intake
      in triggering CIM. In addition, the positive effects of passive mechanical
      loading on muscle fiber size and force generating capacity was not affected by
      the nutritional status in this study. However, due to the small sample size these
      pilot results need to be validated in a larger cohort. 

PMID- 24887773
TI  - Advanced cell culture techniques for cancer drug discovery.
AB  - Human cancer cell lines are an integral part of drug discovery practices.
      However, modeling the complexity of cancer utilizing these cell lines on standard
      plastic substrata, does not accurately represent the tumor microenvironment.
      Research into developing advanced tumor cell culture models in a three
      dimensional (3D) architecture that more prescisely characterizes the disease
      state have been undertaken by a number of laboratories around the world. These 3D
      cell culture models are particularly beneficial for investigating mechanistic
      processes and drug resistance in tumor cells. In addition, a range of molecular
      mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor
      cells cultured in two-dimensional monolayer conditions do not respond to cancer
      therapeutics/compounds in a similar manner. Recent studies have demonstrated the
      potential of utilizing 3D cell culture models in drug discovery programs;
      however, it is evident that further research is required for the development of
      more complex models that incorporate the majority of the cellular and physical
      properties of a tumor. 

PMID- 24887776
TI  - Iatrogenic profunda femoris stenosis after superficial femoral artery stenting.

PMID- 24887778
TI  - Laparoscopic duodenojejunostomy for management of superior mesenteric artery
      syndrome.

PMID- 24887777
TI  - Intra-abdominal actinomycosis in association with sigmoid diverticulitis.

PMID- 24887779
TI  - Francis F. Maury, M.D. (1840 to 1879): an often forgotten pioneer in early
      American surgery.

PMID- 24887780
TI  - Prospective evaluation of serial hemoglobin values during the initial trauma
      evaluation.

PMID- 24887781
TI  - Splenosis in the context of multiple endocrine neoplasia syndrome 1.

PMID- 24887782
TI  - Laparoscopic parastomal hernia repair with titanium-coated mesh: technique
      principles and personal experiences.

PMID- 24887783
TI  - Gallbladder small lymphocytic lymphoma in a patient with chronic cholecystitis
      and choledocholithiasis.

PMID- 24887784
TI  - The management of a complex bile duct injury after laparoscopic cholecystectomy.

PMID- 24887785
TI  - Litigation in laparoscopic cholecystectomies.

PMID- 24887786
TI  - Traumatic bronchobiliary fistula.

PMID- 24887787
TI  - Contemporary management of flail chest.
AB  - Thoracic injury is currently the second leading cause of trauma-related death and
      rib fractures are the most common of these injuries. Flail chest, as defined by
      fracture of three or more ribs in two or more places, continues to be a
      clinically challenging problem. The underlying pulmonary contusion with
      subsequent inflammatory reaction and right-to-left shunting leading to hypoxia
      continues to result in high mortality for these patients. Surgical stabilization
      of the fractured ribs remains controversial. We review the history of management
      for flail chest alone and when combined with pulmonary contusion. Finally, we
      propose an algorithm for nonoperative and surgical management. 

PMID- 24887788
TI  - Ambroise Pare (1510 to 1590): a surgeon centuries ahead of his time.
AB  - In their extensive writings, Hippocrates and Celsus counseled physicians to be
      knowledgeable in both the medical and surgical management of patient recovery.
      However, their words fell by the wayside because cutting of the body was
      forbidden by the Roman Catholic Church. Furthermore, the contemporaneous Arabic
      medical teachings emphasized tradition and authority over observation and
      personal experience. This created an ever-growing rift between the schools of
      surgical and pharmacologic medicine with both groups denying their involvement in
      the other domain. Surgeons had been plagued by postoperative complications
      including infection, malnutrition, and muscular wasting for centuries. Surgeons
      were forced to re-examine how diet and exercise affected outcomes before the
      advent of microbiology and advances in pharmacology. All of this changed when
      Ambroise Pare, a 16th century surgeon, revolutionized the medical world with his
      astute observations of postoperative diet and exercise. 

PMID- 24887789
TI  - Current screening guidelines overlook a significant number of patients treated
      for colorectal cancer.
AB  - The U.S. Preventive Services Task Force (USPSTF) recommends screening for
      colorectal cancer (CRC) in adults, beginning at age 50 years and continuing until
      age 75 years. Screening has led to a decreased incidence of CRC in this subset of
      patients. Despite these improvements, there has been a significant increase in
      the incidence of CRC in patients aged 20 to 49 years and those older than age 75
      years. We sought to evaluate the appropriateness of the current screening
      guidelines as it pertained to our patient demographic at Greenville Health
      System. We retrospectively reviewed the Greenville Health System tumor registry
      from January 2005 to December 2010. Age at diagnosis, pathologic stage, tumor
      location, and demographic information were obtained on patients treated for CRC.
      Data points were stratified across the three age distributions used by the
      USPSTF. Greater than one-third (34.7%) of patients diagnosed with CRC fell
      outside of the recommended screening ages. Fifty-eight per cent of patients
      younger than 50 years old had advanced disease at diagnosis, Stage III or IV, as
      compared with other groups. Two hundred eight of the 708 patients (29.3%) were
      diagnosed on screening colonoscopy, whereas 500 patients (70.7%) were found to
      have CRC on diagnostic colonoscopy or at the time of operation for related
      complications. There are a significant number of patients who are ultimately
      treated for CRC that would fall outside the recommended screening parameters at
      our institution. Re-evaluation of the current CRC screening guidelines and risk
      factor assessment is needed to account for the changing trends. 

PMID- 24887790
TI  - Trisectionectomy for cholangiocarcinoma: is it worth it?
AB  - Many centers perform aggressive liver resection for patients with
      cholangiocarcinoma, because improved survival has been reported after resection
      with negative margins. Patients with extensive tumor burden sometimes require
      trisectionectomy for clearance of disease with increased risk of liver
      insufficiency and postoperative complications. A retrospective review was
      conducted examining records for 62 patients who were taken to the operating room
      for cholangiocarcinoma from January 1, 2000, to March 31, 2010. Thirty-eight
      patients underwent surgical resection: 17 patients underwent trisectionectomy and
      21 patients underwent liver resections. No statistically significant differences
      were found between patients who underwent liver resection compared with those who
      underwent trisectionectomy with regard to demographics or complications.
      Pathology was rereviewed by a single pathologist, and no statistically
      significant differences were found between the two groups in any of the recorded
      pathology results. No significant differences in survival were found between the
      two groups. The median survival for liver resection patients was 2.9 years and
      for trisegmentectomy patients was 2.8 years. Complete resection with negative
      margins remains the current surgical goal in the treatment for
      cholangiocarcinoma. Performing trisectionectomy in an effort to clear all disease
      is safe with comparable outcomes to patients needing less extensive liver
      resections. 

PMID- 24887791
TI  - Pneumoperitoneum after virtual colonoscopy: causes, risk factors, and management.
AB  - Computed tomographic virtual colonoscopy (CTVC) is a safe and minimally invasive
      modality when compared with fiberoptic colonoscopy for evaluating the colon and
      rectum. We have reviewed the risks for colonic perforation by investigating the
      relevant literature. The objectives of this study were to assess the risk of
      colonic perforation during CTVC, describe risk factors, evaluate ways to reduce
      the incidence complications, and to review management and treatment options. A
      formal search of indexed publications was performed through PubMed. Search
      queries using keywords "CT colonography," "CT virtual colonoscopy," "virtual
      colonoscopy," and "perforation" yielded a total of 133 articles. A total of eight
      case reports and four review articles were selected. Combining case reports and
      review articles, a total of 25 cases of colonic perforation after CTVC have been
      reported. Causes include, but are not limited to, diverticular disease, irritable
      bowel diseases, obstructive processes, malignancies, and iatrogenic injury. Both
      operative and nonoperative management has been described. Nonoperative management
      has been proven safe and successful in minimally symptomatic and stable patients.
      Colonic perforation after CTVC is a rare complication and very few cases have
      been reported. Several risk factors are recurrent in the literature and must be
      acknowledged at the time of the study. Management options vary and should be
      tailored to each individual patient. 

PMID- 24887792
TI  - Associations between Charlson Comorbidity Index and surgical risk severity and
      the surgical outcomes in advanced-age patients.
AB  - The Charlson Comorbidity Index (CCI) has not been assessed for elderly (95 years
      of age or older) surgical patients. We examined the association between the CCI
      and life-threatening complications and 30-day mortality rate. Medical records of
      patients 95 years old or older from 2004 through 2008 were reviewed for major
      postoperative morbidity or death. Logistic regression analyses of age, sex, the
      CCI, American College of Cardiology/American Heart Association Surgical Risk
      Stratification, and surgical urgency were performed to identify associations with
      poor surgical outcome. One hundred eighty-seven patients were identified (mean
      [standard deviation] age, 96.6 [1.9] years; median [interquartile range] CCI, 4
      [2 to 6]). Ninety patients (48.1%) underwent moderate-risk and 20 (10.7%)
      underwent high-risk surgical procedures. Twenty patients (10.7%) died within 30
      postoperative days and 20 others had major morbidity. Only moderate-risk (P =
      0.045) and high-risk surgical procedures (P = 0.001) were associated with poor
      outcome. Patients of advanced age have high rates of morbidity and death after
      surgical procedures. These events are associated with surgical risk
      stratification and are independent of patient comorbidities. Risks, benefits, and
      alternatives must be considered carefully and discussed with patients and their
      families before deciding to proceed with high-risk surgery. 

PMID- 24887793
TI  - The impact of regionalization of pancreaticoduodenectomy for pancreatic Cancer in
      North Carolina since 2004.
AB  - Pancreaticoduodenectomy (PD) carries a significant risk. High-volume centers
      (HVCs) provide improved outcomes and regionalization is advocated. Rapid
      regionalization could, however, have detrimental effects. North Carolina has
      multiple HVCs, including an additional HVC added in late 2006. We investigated
      regionalization of PD and its effects before, and after, the establishment of
      this fourth HVC. The North Carolina Hospital Discharge Database was queried for
      all PDs performed during 2004 to 2006 and 2007 to 2009. Hospitals were
      categorized by PD volume as: low (one to nine/year), medium (10 to 19/year), and
      high (20/year or more). Mortality and major morbidity was assessed by comparing
      volume groups across time periods. Number of PDs for cancer increased 91 per cent
      (129 to 246 cases) at HVCs, whereas decreasing at low-volume (62 to 58 cases) and
      medium-volume (80 to 46 cases) centers. Percentage of PD for cancer performed at
      HVCs increased significantly (47.6 to 70.3%) while decreasing for low- and medium
      volume centers (P < 0.001). Mortality was significantly less at HVCs (2.8%)
      compared with low-volume centers (10.3%) for 2007 to 2009. Odds ratio for
      mortality was significantly lower at HVCs during 2004 to 2006 (0.31) and 2007 to
      2009 (0.34). Mortality for PD performed for cancer decreased from 6.6 to 4.6 per
      cent (P = 0.31). Major morbidity was not significantly different between groups
      within either time period; however, there was a significant increase in major
      morbidity at low-volume centers (P = 0.018). Regionalization of PD for cancer is
      occurring in North Carolina. Mortality was significantly lower at HVCs, and rapid
      regionalization has not detracted from the superior outcomes at HVCs. 

PMID- 24887794
TI  - A prospective, controlled evaluation of the abdominal reapproximation anchor
      abdominal wall closure system in combination with VAC therapy compared with VAC
      alone in the management of an open abdomen.
AB  - Dramatic increases in damage control and decompressive laparotomies and a
      significant increase in patients with open abdominal cavities have resulted in
      numerous techniques to facilitate fascial closure. We hypothesized addition of
      the abdominal reapproximation anchor system (ABRA) to the KCI Abdominal Wound
      VacTM (VAC) or KCI ABTheraTM would increase successful primary closure rates and
      reduce operative costs. Fourteen patients with open abdomens were prospectively
      randomized into a control group using VAC alone (control) or a study group using
      VAC plus ABRA (VAC-ABRA). All patients underwent regular VAC changes; patients
      receiving VAC-ABRA also underwent concomitant daily elastomer adjustment of the
      ABRA system. Primary end points included abdominal closure, number of operating
      room (OR) visits, and OR time use. Eight patients were included in the VAC-ABRA
      group and six patients in the control group. Primary closure rates between groups
      were not statistically different; however, the number of trips to the OR and OR
      time use were different. Despite higher Acute Physiology and Chronic Health
      Evaluation II scores, larger starting wound size, and higher rates of abdominal
      compartment syndrome, closure rates in the VAC-ABRA group were similar to VAC
      alone. Importantly, however, fewer OR trips and less OR time were required for
      the VAC-ABRA group.

PMID- 24887795
TI  - Letting the sun set on small bowel obstruction: can a simple risk score tell us
      when nonoperative care is inappropriate?
AB  - Controversy remains as to which patients with small bowel obstruction (SBO) need
      immediate surgery and which may be managed conservatively. This study evaluated
      the ability of clinical risk factors to predict the failure of nonoperative
      management of SBO. The electronic medical record was used to identify all
      patients with SBO over one year. Clinical, laboratory, and imaging data were
      recorded. Univariate and multivariable analyses were performed to identify risk
      factors predicting need for surgery. Cox proportional hazards regression was used
      to identify risk factors that influence need and timing for surgery. Two hundred
      nineteen consecutive patients were included. Most patients did not have a prior
      history of SBO (75%), radiation therapy (92%), or cancer (70%). The majority had
      undergone previous abdominal or pelvic surgery (82%). Thirty-five per cent of
      patients ultimately underwent laparotomy. Univariate analysis showed that
      persistent abdominal pain, abdominal distention, nausea and vomiting, guarding,
      obstipation, elevated white blood cell count, fever present 48 hours after
      hospitalization, and high-grade obstruction on computed tomography (CT) scan were
      significant predictors of the need for surgery. Multivariable analysis revealed
      that persistent abdominal pain or distention (hazard ratio [HR], 3.04; P =
      0.013), both persistent abdominal pain and distention (HR, 4.96; P < 0.001),
      fever at 48 hours (HR, 3.66; P = 0.038), and CT-determined high-grade obstruction
      (HR, 3.45; P = 0.017) independently predicted the need for surgery. Eighty-five
      per cent of patients with none of these four significant risk factors were
      successfully managed nonoperatively. Conversely, 92 per cent of patients with
      three or more risk factors required laparotomy. This analysis revealed four
      readily evaluable clinical parameters that may be used to predict the need for
      surgery in patients presenting with SBO: persistent abdominal pain, abdominal
      distention, fever at 48 hours, and CT findings of high-grade obstruction. These
      factors were combined into a predictive model that may of use in predicting
      failure of nonoperative SBO management. Early operation in these patients should
      decrease length of stay and diagnostic costs. 

PMID- 24887796
TI  - Prospective clinical trial of surgical intervention for painful rib fracture
      nonunion.
AB  - We performed a prospective clinical trial of resection with or without plate
      fixation for symptomatic rib fracture nonunion three or more months postinjury
      with 6-month postoperative followup. The McGill Pain Questionnaire (MPQ) and RAND
      36 Health Survey were administered and activity level (sedentary, ambulatory,
      moderately active, vigorous), functional status (disabled, nonphysical labor,
      physical labor), and work status (employed, unemployed, retired, student) were
      queried pre- and postoperatively. Twenty-four patients 4 to 197 months (median,
      16 months) postinjury underwent surgical intervention for one to four rib
      fracture nonunions (median, two nonunions). Evidence of intercostal nerve
      entrapment was present in nine patients (38%). MPQ Present Pain Intensity and
      Pain Rating Index and RAND 36 Physical Functioning, Role Physical, Social
      Functioning, Role Social, Bodily Pain, Vitality, Mental Health, and General
      Health were significantly improved at six months compared with study entry (P <
      0.05). Activity levels significantly improved (P < 0.0001) but functional and
      work status did not change. Twenty-four-hour morphine equivalent dosage of
      opioids at study entry was 20.3 +/- 30.8 (mean +/- standard deviation) and at
      study completion was 9.4 +/- 17.5 (P = 0.054). Complications included one wound
      infection, two partial screw backouts, and one chest wall hernia at one year
      after resection of adjacent nonunions with significant gaps repaired with
      absorbable plates. Surgical intervention for rib fracture nonunion may improve
      chronic pain and disability but without change in functional or work status.
      Resection of adjacent nonunions with significant gaps may lead to chest wall
      hernia. 

PMID- 24887797
TI  - The role of the undermining during circular excision of secondary intention
      healing.
AB  - Circular excision by secondary intention healing is useful for small skin
      defects. The study compared the effect of the neighboring undermining on wound
      healing. Patients undergoing circular excision (diameters less than 20 mm) were
      divided into four groups in sequence by the range of neighboring subcutaneous
      undermining. Key outcome measures were complication rate, healing time, mature
      scar width, and quality. Statistical differences between different undermining
      types were assessed. Six hundred twenty-eight patients were randomized. No
      complication rates differed among undermining types. Groups 4 (range 15 mm) and 3
      (range 10 mm) did not differ in healing time but healed faster than Group 2
      (range 5 mm); the slowest was Group 1 (range 0 mm). Scar width measured declined
      from Group 1 to Group 4. The visual assessment of mature scars rating increased
      gradually, including Groups 1, 2, 3, and 4, but there was no difference between
      Groups 3 and 4. The undermining of the surrounding tissue is useful to promote
      secondary intention healing of small skin defects and to improve the cosmetic
      results of the final scar. The study compared the effect of neighboring
      undermining on wound secondary healing of circular excision. Key outcome measures
      were complication rate, healing time, mature scar width, and quality. Statistical
      differences between different undermining types were used. 

PMID- 24887798
TI  - Prevalence and predictors of nonalcoholic steatohepatitis in obese patients
      undergoing bariatric surgery: a Department of Defense experience.
AB  - Nonalcoholic steatohepatitis (NASH) is a silent liver disease that can lead to
      inflammation and subsequent scaring. If left untreated, cirrhosis may ensue.
      Morbidly obese patients are at an increased risk of NASH. We report the
      prevalence and predictors of NASH in patients undergoing morbid obesity surgery.
      A retrospective review was conducted on morbidly obese patients undergoing weight
      reduction surgery from September 2005 through December 2008. A liver biopsy was
      performed at the time of surgery. Patients who had a history of hepatitis
      infection or previous alcohol dependency were excluded. Prevalence of NASH was
      studied. Predictors of NASH among clinical and biochemical variables were
      analyzed using multivariate regression analysis. One hundred thirteen patients
      were analyzed (84% female; mean age, 42.6 +/- 11.4 years; mean body mass index,
      45.1 +/- 5.7 kg/m(2)). Sixty-one patients had systemic hypertension (54%) and 35
      patients had diabetes (31%). The prevalence of NASH in this study population was
      35 per cent (40 of 113). An additional 59 patients (52%) had simple steatosis
      without NASH. Only 14 patients had normal liver histology. On multivariate
      analysis, only elevated aspartate aminotransferase (AST) (greater than 41 IU/L)
      was the independent predictor for NASH (odds ratio, 5.85; confidence interval,
      1.06 to 32.41). Patient age, body mass index, hypertension, diabetes,
      hypercholesterolemia, and abnormal alanine aminotransferase did not predict NASH.
      NASH is a common finding in obese population. Abnormal AST was the only
      predictive factor for NASH. 

PMID- 24887799
TI  - Emergency management of complicated jejunal diverticulosis.
AB  - Jejunal diverticulosis is a rare condition that is usually found incidentally. It
      is most often asymptomatic but presenting symptoms are nonspecific and include
      abdominal pain, nausea, diarrhea, malabsorption, bleeding, obstruction, and/or
      perforation. A retrospective review of medical records between 1999 and 2012 at a
      tertiary referral center was conducted to identify patients requiring emergency
      management of complicated jejunal diverticulosis. Complications were defined as
      those that presented with inflammation, bleeding, obstruction, or perforation.
      Eighteen patients presented to the emergency department with acute complications
      of jejunal diverticulosis. Ages ranged from 47 to 86 years (mean, 72 years).
      Seven patients presented with evidence of free bowel perforation. Six had either
      diverticulitis or a contained perforation. The remaining five were found to have
      gastrointestinal bleeding. Fourteen of the patients underwent surgical
      management. Four patients were successfully managed nonoperatively. As a result
      of the variety of presentations, complications of jejunal diverticulosis present
      a diagnostic and therapeutic challenge for the acute care surgeon. Although
      nonoperative management can be successful, most patients should undergo surgical
      intervention. Traditional management dictates laparotomy and segmental jejunal
      resection. Diverticulectomy is not recommended as a result of the risk of staple
      line breakdown. The entire involved portion of jejunum should be resected when
      bowel length permits. 

PMID- 24887800
TI  - Life expectancy after curative-intent treatment of breast cancer: impact on long
      term follow-up care.
AB  - Long-term survival rates after treatment for breast cancer are directly
      influenced by early deaths resulting from disease. For longer-term breast cancer
      survivors, survival rates appear deceptively low. We hypothesize that the actual
      survival curve for long-term survivors approaches the overall survival of the
      general population. The Surveillance, Epidemiology, and End Results database
      (1988 to 2002) was used to identify patients with nonmetastatic breast cancer who
      underwent definitive surgical treatment. The survival of the general population
      was constructed by using national life tables with an age-matched population.
      Comparisons of survivals were made for 3-, 5-, and 7-year breast cancer survivor
      cohorts. Of 237,180 patients, 92.4 per cent survived three years, 82.1 per cent
      five years, and 58.1 per cent seven years. Stage I patients have equivalent or
      better survivals compared with the age-matched general population in all three
      cohorts. Stage II patients reached equivalent conditional survival between eight
      and nine years after diagnosis regardless of cohort. Stage III patients required
      achieving nine to 10 years after diagnosis to achieve equivalent survival
      probability, except in 7-year survivors, in whom 10 to 11 years was required. In
      all stages, once equivalence was reached, survival exceeded the general
      population over the remaining years. Initial cancer stage influences overall
      survival for many years after diagnosis. Patients with Stage I cancer return to
      the general population risk as early as three years after diagnosis, whereas
      higher stages can require up to nine years to achieve parity with a more
      generalized population. These findings should be factored into general health
      screening issues for long-term breast cancer survivors. 

PMID- 24887801
TI  - Patients with blunt head trauma on anticoagulation and antiplatelet medications:
      can they be safely discharged after a normal initial cranial computed tomography
      scan?
AB  - The literature reports delayed intracranial hemorrhage (ICH) after blunt trauma
      in patients taking preinjury anticoagulant and antiplatelet (AC/AP) medications.
      We sought to evaluate the incidence of delayed ICH at our institution and
      hypothesize that patients taking AC/AP medications who are found to have a
      negative first computed tomography (CT) scan will not require a second CT scan. A
      total of 303 patients were retrospectively reviewed. Age, gender, mechanism of
      injury, international normalized ratio (INR), initial and secondary cranial CT
      findings, and outcomes were recorded. One hundred sixty-eight (55.4%) were found
      to be taking AP/AC medications. Ninety-six (57%) were male and 72 (43%) female.
      Aspirin use was 42.8 per cent (72 of 168), clopidogrel next (39 of 168 [23.0%]),
      and warfarin least (18 of 168 [10.7%]). One hundred sixty-six (98.8%) presented
      with significant findings on the first CT scan. Fourteen (87.5%) of the 16
      patients with an INR 2.0 or higher presented with an ICH on the first CT. Ninety
      percent of patients with an INR 1.5 or higher presented with positive findings on
      the first CT scan. One hundred per cent of patients with an INR 3.0 or higher
      presented with an ICH on the first CT scan. The incidence of a delayed ICH was
      two of 168 (1.19%). Of those two patients with a delayed ICH, 100 per cent were
      taking warfarin and had an INR greater than 2.0. The incidence of delayed ICH was
      1.19 per cent. The protocol requiring a second CT scan for all patients on AC/AP
      medications after a negative first CT scan should be questioned. For patients
      with blunt head trauma taking warfarin or a warfarin-aspirin combination, a
      repeat cranial CT scan after a negative initial CT is acceptable. For patients
      taking clopidogrel, a period of observation may be warranted. 

PMID- 24887802
TI  - Patience is a virtue: an argument for delayed surgical intervention in fulminant
      Clostridium difficile colitis.
AB  - Recently, the incidence and severity of Clostridium difficile infection (CDI) has
      increased. In cases of fulminant infection, surgery is a viable therapeutic
      option but associated with high mortality. We sought to examine factors
      associated with mortality in a large sample of patients with severe CDI that
      underwent surgery. A retrospective study was conducted in patients with severe
      CDI undergoing colectomy. Demographics, risk factors, comorbidities, clinical and
      laboratory data, and time between admission/diagnosis of CDI and colectomy were
      collected. Conventional markers of severity were evaluated as predictors of
      mortality. Sixty-four cases were included for analysis. The overall observed
      mortality rate was 45.3 per cent. Few conventional markers of severity were
      significantly associated with mortality. Risk factors that correlated with
      postsurgical mortality were vasopressor use (odds ratio, 3.08; 95% confidence
      interval, 1.00 to 9.92) and shorter time between diagnosis and surgery (median
      time, 2 vs 3 days, P = 0.009). This study suggests that a delay in surgery after
      diagnosis of severe CDI may improve overall outcomes. The finding regarding
      timing of surgery is contrary to traditional teaching and may be the result of
      improved medical treatment and stabilization before surgery. Consideration should
      be given to the importance of timing of colectomy in fulminant CDI, whereas
      prospective studies should be conducted to elucidate causal relationships. 

PMID- 24887803
TI  - Concerning trends in Appalachian patients with thyroid carcinoma.

PMID- 24887804
TI  - Atrial fibrillation in elderly burn patients.

PMID- 24887805
TI  - Consultation for 'dead gut': who needs an emergent exploratory laparotomy?

PMID- 24887806
TI  - Is computed tomography reliable for the evaluation of cervical spine injury in
      obese patients?

PMID- 24887808
TI  - Exposing nanobubble-like objects to a degassed environment.
AB  - The primary attribute of interest of surface nanobubbles is their unusual
      stability and a number of theories trying to explain this have been put forward.
      Interestingly, the dissolution of nanobubbles is a topic that did not receive a
      lot of attention yet. In this work we applied two different experimental
      procedures which should cause gaseous nanobubbles to completely dissolve. In our
      experiments we nucleated nanobubble-like objects by putting a drop of water on
      HOPG using a plastic syringe and a disposable needle. In method A, the nanobubble
      like objects were exposed to a flow of degassed water (1.17 mg l(-1)) for 96
      hours. In method B, the ambient pressure was lowered in order to degas the liquid
      and the nanobubble-like objects. Interestingly, the nanobubble-like objects
      remained stable after exposure to both methods. After thorough investigation of
      the procedures and materials used during our experiments, we found that the
      nanobubble-like objects were induced by the use of disposable needles in which
      PDMS contaminated the water. It is very important for the nanobubble community to
      be aware of the fact that, although features look and behave like nanobubbles, in
      some cases they might in fact be induced by contamination. The presence of
      contamination could also resolve some inconsistencies found in the nanobubble
      literature. 

PMID- 24887807
TI  - Magnetic sensing technology for molecular analyses.
AB  - Magnetic biosensors, based on nanomaterials and miniature electronics, have
      emerged as a powerful diagnostic platform. Benefiting from the inherently
      negligible magnetic background of biological objects, magnetic detection is
      highly selective even in complex biological media. The sensing thus requires
      minimal sample purification and yet achieves a high signal-to-background
      contrast. Moreover, magnetic sensors are also well-suited for miniaturization to
      match the size of biological targets, which enables sensitive detection of rare
      cells and small amounts of molecular markers. We herein summarize recent advances
      in magnetic sensing technologies, with an emphasis on clinical applications in
      point-of-care settings. Key components of sensors, including magnetic
      nanomaterials, labeling strategies and magnetometry, are reviewed. 

PMID- 24887809
TI  - Gestational and lactational exposure to the polychlorinated biphenyl mixture
      Aroclor 1254 modulates retinoid homeostasis in rat offspring.
AB  - Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic
      effects in mammals including alterations of the vital retinoid (vitamin A)
      system. The aim of this study was to characterize alterations of tissue retinoid
      levels in rat offspring and their dams following gestational and lactational
      exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the
      interrelationship of these changes with other established sensitive biochemical
      and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or
      15 mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND)
      23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77
      and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes
      and serum thyroid hormones were analyzed. A multivariate regression between A1254
      treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid
      hormone levels and body/liver weights was performed using an orthogonal partial
      least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of
      A1254 to the observed effects was also estimated using the toxic equivalency
      (TEQ) concept. In both male and female offspring short-term alterations in tissue
      retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and
      retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent
      increases in hepatic and renal all-trans-RA levels. Long-term changes consisted
      of decreased hepatic retinyl palmitate and increased renal retinol levels that
      were apparent until PND350. Retinoid system alterations were associated with
      altered CYP enzyme activities and serum thyroid hormone levels as well as body
      and liver weights in both offspring and dams. The estimated DL activity was
      within an order of magnitude of the theoretical TEQ for different endpoints,
      indicating significant involvement of DL congeners in the observed effects. This
      study shows that tissue retinoid levels are affected both short- and long-term by
      developmental A1254 exposure and are associated with alterations of other
      established endpoints of toxicological concern.

PMID- 24887810
TI  - Unusual coexistence of pulmonary sclerosing hemangioma and pericardial cyst.
AB  - Pulmonary sclerosing hemangioma is an uncommon tumor, thought to be a benign
      neoplasm. Pericardial cysts are also uncommon benign abnormalities, most often
      found incidentally on chest radiography. We describe the case of a 51-year-old
      woman in whom both lesions were incidentially detected on a routine chest
      radiograph. Enucleation of the pulmonary sclerosing hemangioma and simultaneous
      resection of the pericardial cyst were undertaken. 

PMID- 24887811
TI  - A bailout approach: Transaxillary Impella implantation in toxic cardiomyopathy.
AB  - The femoral artery has been the traditional approach for implantation of the
      Impella left ventricular assist device. We describe the case of a young man with
      toxic (cocaine-related) cardiomyopathy, severe left ventricular dysfunction, and
      moderate mitral insufficiency who received a transfemoral Impella left
      ventricular assist device that was relocated to the right axillary artery due to
      uncontrolled femoral access bleeding. The patient immediately stabilized post
      implantation and was successfully bridged to a full recovery 6 days later. 

PMID- 24887812
TI  - Hybrid repair of right aortic arch aneurysm with a Kommerell's diverticulum.
AB  - We describe the case of a 74-year-old man who underwent a hybrid open and
      endovascular approach for repair of dissecting thoracic aortic aneurysm of a
      right aortic arch with aberrant left subclavian artery arising from a Kommerell's
      diverticulum. Total debranching using a tailored quadrifurcated graft and
      thoracic endovascular aneurysm repair for the transverse aortic lesion were
      performed. The procedures were successfully accomplished with complete exclusion
      of the aneurysm. This hybrid procedure for complex aortic arch disease may reduce
      perioperative complications compared to challenging conventional open approaches.

PMID- 24887813
TI  - Anterior and posterior papillary muscle rupture after myocardial infarction.
AB  - A 66-year-old man was referred in cardiogenic shock due to acute myocardial
      infarction. Echocardiography revealed severe mitral regurgitation with prolapse
      of the posterior mitral leaflet due to papillary muscle rupture. Emergency
      coronary angiography showed subtotal occlusion of the left circumflex coronary
      artery. A percutaneous coronary intervention was performed immediately. After
      inducing percutaneous cardiopulmonary support, emergency mitral valve replacement
      was carried out. The anterior and posterior papillary muscles attached to the
      posterior mitral leaflet were completely ruptured. Pathological findings showed
      massive necrosis. 

PMID- 24887814
TI  - Ascending aorta thrombus: A diagnostic and treatment dilemma.
AB  - Due to its position, a mass lesion in the ascending aorta poses a diagnostic and
      treatment dilemma. We describe the management of a symptomatic mass in the
      ascending aorta in a 35-year-old man who presented with a cerebrovascular
      accident. 

PMID- 24887816
TI  - Primary cardiac synovial sarcoma. A rare tumor with poor prognosis.
AB  - Synovial sarcoma comprises approximately 10% of all soft tissue tumors. Primary
      cardiac synovial sarcoma is exceedingly rare and accounts for<1% of all primary
      cardiac tumors. These tumors are highly aggressive with survival<1 year, even
      with surgery, chemotherapy, or radiation. We describe the case of a 45-year-old
      gentleman with primary cardiac synovial sarcoma of the heart, metastasizing to
      the lung. The tumor was resected, and the patient underwent chemotherapy with
      regression of the lung nodules.

PMID- 24887815
TI  - Prosthesis-sparing aortic root replacement following aortic valve replacement.
AB  - Reoperation on the aortic root is considered to be challenging because of high
      hospital mortality. Prosthesis-sparing aortic root replacement, in which the
      aortic prosthesis is preserved during reoperation, and could avoid passing
      sutures through the weakened aortic annuls after the initial prosthesis has been
      removed. We report 3 cases of prosthesis-sparing aortic root replacement. Prior
      procedures were aortic valve replacement and the Bentall operation 14 to 35 years
      previously. Postoperative courses were uneventful, with no signs of
      pseudoaneurysm or valve malfunction observed during follow-up periods of 93 to
      360 days. 

PMID- 24887817
TI  - Acute aortic syndrome mimicking intramural hematoma with hemopericardium.
AB  - We report a case of acute aortic syndrome in a 64-year-old man who presented with
      chest pain and hypotension. His electrocardiogram and cardiac troponins were
      normal. Computed tomography showed hemopericardium of 2.4 cm, but no aortic
      intimal tear. At surgery, the portion of the aorta affected by adventitial
      hemorrhage was replaced with a Dacron graft. A nonpenetrating ulcerated plaque
      was also observed. Massive bleeding through the chest drains with hypotension
      required emergency reoperation in the intensive care unit. The patient was
      discharged home on postoperative day 11.

PMID- 24887818
TI  - Full-metal jacket: A bad strategy.
AB  - Although drug-eluting stents are increasingly used to treat coronary disease,
      restenosis remains the major limitation of these devices. We report a case of
      complete metal jacket using 17 stents for triple-vessel coronary disease in a 73
      year-old man, for whom surgery would have been the best choice. 

PMID- 24887819
TI  - Double-valve surgery in Shprintzen-Goldberg syndrome.
AB  - We describe the challenging case of a 28-year-old Jehovah's Witness patient who
      presented with symptomatic mitral and tricuspid valve disease and Shprintzen
      Goldberg syndrome. This is the first reported double-valve surgery in such a
      patient who, apart from chest deformity, had a small body size, severe lung
      disease, difficult airway and vascular access, and to add to the complexity,
      refused blood and blood product use. The patient underwent a successful mitral
      valve replacement and tricuspid valve repair through a right thoracotomy. Apart
      from atrial fibrillation, he had a smooth hospital course and was discharged home
      on postoperative day 9. 

PMID- 24887820
TI  - A case of ventricular septal defect and mitral insufficiency after blunt trauma.
AB  - Few reports have described traumatic heart injury in children. We describe a case
      of acute mitral regurgitation associated with papillary muscle rupture, traumatic
      ventricular septal defect, and impending left ventricular free wall rupture due
      to blunt trauma in a 2-year-old girl. The papillary muscle was sutured to the
      left ventricular free wall. The septal defect and surrounding ruptured muscle
      were covered with a pericardial patch, and a Hemashield patch was used to close
      the ventriculotomy. A residual defect caused by dehiscence of the pericardial
      patch necessitated reoperation 10 months later. The patient is currently being
      observed on an outpatient basis. 

PMID- 24887821
TI  - A rare variety of mixed total anomalous pulmonary venous connection.
AB  - We describe a rare case of mixed supra- and infracardiac total anomalous
      pulmonary venous connection in a 2-month-old boy weighing 2.3 kg who was admitted
      with central cyanosis. Although the surgical repair was successful, the child
      died due to pulmonary hypertensive crisis.

PMID- 24887822
TI  - 18F-fluorodeoxyglucose uptake in subclavian artery and aorta in aortitis
      syndrome.

PMID- 24887823
TI  - Alternative redo sternotomy in a patient with tracheostoma and patent grafts.
AB  - We describe a redo mitral valve replacement operation in a 71-year-old man with a
      tracheostoma and patent bypass grafts to the coronary arteries. Preoperative
      investigations revealed that the patent right internal thoracic artery graft ran
      directly under the sternum just anterior to the ascending aorta, and a saphenous
      vein graft was adhering to a surgical wire. To prevent injury to the patent
      grafts and cardiac structures, and to avoid communication with the tracheostoma,
      the redo procedure was performed via an anterior minithoracotomy combined with a
      low T-shaped partial sternotomy. The reoperation was successfully completed
      without any complications. 

PMID- 24887824
TI  - One-stage repair of tetralogy of Fallot with coarctation of the aorta.
AB  - We describe the rare case of a 10-month-old girl who had coarctation of the aorta
      in association with tetralogy of Fallot. The surgical management and
      postoperative course is described. This case highlights the rare association of
      coarctation with tetralogy of Fallot, with a large intracardiac right-to-left
      shunt. Although an exception to the rule, it challenges the reduced fetal blood
      flow theory and the smooth muscle cell migration theory as embryological
      explanations for the development of coarctation. 

PMID- 24887825
TI  - Giant leiomyosarcoma of inferior vena cava. A surgical challenge.
AB  - We describe the case of a 37-year-old woman who presented with an unusually large
      (26 * 20 * 16 cm) extraluminal leiomyosarcoma arising from segment I (below the
      renal vessels) of the inferior vena cava. She was successfully managed with
      radical surgical excision and reconstruction of the inferior vena cava with
      synthetic graft.

PMID- 24887826
TI  - Complex transposition repair with aortic arch hypoplasia: a simple technique.
AB  - A modified technique of interdigitating aortic arch reconstruction was used
      successfully to treat 8 patients with complex congenital heart disease including
      transposition of the great arteries, ventricular septal defect, or Taussig-Bing
      anomalies combined with aortic arch hypoplasia and coarctation of the aorta,
      without the need for homograft tissue. 

PMID- 24887827
TI  - Concomitant coronary bypass and below knee amputation in a diabetic patient.
AB  - A 57-year-old man presented with unstable angina and uncontrolled diabetes with
      diabetic foot. It was decided to perform right below knee amputation with
      coronary revascularization in a single stage. Right below knee amputation was
      carried out first. The left anterior descending artery, ramus intermedius, and
      second obtuse marginal branch of the circumflex were bypassed on a beating heart,
      using saphenous vein grafts. The patient was discharged on the 7th postoperative
      day after a course of antibiotics. 

PMID- 24887828
TI  - Lethal mass mimicking myxoma in the heart.
AB  - A 70-year-old man presented in advanced heart failure with jaundice.
      Transthoracic echocardiography revealed a 21 * 24-mm mass in the left atrium
      attached to the posterior mitral valve leaflet. Surgical excision was attempted,
      but the tumor had infiltrated the entire left atrial wall and was deemed too
      extensive to be resectable. Histology confirmed a high-grade pleomorphic sarcoma
      with malignant fibrous histiocytoma-like features. Liver biopsy revealed a high
      grade liver sarcoma. 

PMID- 24887829
TI  - Urgent surgery for cardiac hydatid cyst located in interventricular septum.
AB  - A 6-year-old girl was referred with acute chest pain and dyspnea. Transthoracic
      echocardiography revealed a single large well-defined intramyocardial cystic mass
      in the interventricular septum. A serologic test was positive for echinococcal
      infection. Urgent open heart surgery was undertaken to remove the cyst, and
      albendazole treatment was started. The postoperative course was satisfactory, and
      the patient was discharged on the 5th postoperative day without any complication.

PMID- 24887830
TI  - A rare cause of superior vena cava syndrome 25 years after cardiac surgery.

PMID- 24887831
TI  - Scimitar syndrome: A rare cause of dyspnea and chest pain.

PMID- 24887832
TI  - Accessory mitral tissue: a rare cause of left ventricular outflow obstruction.

PMID- 24887833
TI  - Giant left ventricular pseudoaneurysm.

PMID- 24887834
TI  - Direct aortic transcatheter valve implantation in a porcelain aorta.
AB  - Transcatheter aortic valve implantation has been designed to treat elderly
      patients with severe aortic stenosis at high risk for surgery, and is generally
      performed retrogradely with vascular access. However, in certain patients, this
      access is either not possible or deemed to carry a high risk of vascular injury.
      We report our experience of a direct aortic approach in a 78-year old man with
      severe aortic stenosis, excluded from standard aortic valve replacement due to a
      porcelain aorta, and affected by severe aortic, iliac-femoral, and subclavian
      arteriopathy, rendering the transfemoral or subclavian approach unemployable. 

PMID- 24887835
TI  - Giant thoracoabdominal ganglioneuroblastoma in a 17-year-old patient.
AB  - The most common malignant neurogenic tumors in children are neuroblastic tumors,
      classified as ganglioneuroblastoma or neuroblastoma. Ganglioneuroblastomas
      usually occur at the sympathetic ganglia in the mediastinum, whereas
      neuroblastomas occur in the abdominal cavity. We describe a case of large
      posterior mediastinal ganglioneuroblastoma extending from the aortic arch to the
      left renal hilum in a 17-year-old boy. Despite chemotherapy, post-treatment
      computed tomography showed disease progression. The patient underwent a
      thoracolaparotomy incision and excision of the tumor. These malignant mediastinal
      tumors can potentially grow to a very large size. If alternative treatment has
      failed, resection can be accomplished with relative safety. 

PMID- 24887836
TI  - Solitary intercostal artery aneurysm.

PMID- 24887837
TI  - Coronary revascularization in a patient with dextrocardia and situs inversus.
AB  - A few cases of coronary artery bypass surgery in patients with dextrocardia and
      situs inversus have been reported so far worldwide. This is the first reported
      case from the Gulf region. The operation was performed with the surgeon standing
      on the left side. Grafts included right internal mammary artery to the left
      anterior descending artery, and saphenous vein to the diagonal and obtuse
      marginal arteries. The patient was discharged home after 12 days, with no
      complication. He was doing well after 3 months of follow-up. 

PMID- 24887838
TI  - Management of mycotic femoral artery aneurysm with two resistant organisms.
AB  - We report the management of a case of thigh abscess with ruptured left
      superficial femoral artery mycotic aneurysm in a 91-year-old woman with
      significant comorbidity. The abscess culture grew Escherichia coli and
      Acinetobacter baumannii. Vascular reconstruction was not performed because the
      foot was viable with a heavily contaminated wound. The thigh wound healed with
      the help of vacuum-assisted closure. This is the first report of a ruptured
      mycotic aneurysm of the superficial femoral artery associated with Escherichia
      coli and Acinetobacter baumannii infection. This case demonstrates that resection
      of a mycotic aneurysm without vascular continuity is feasible, especially in
      frail patients. 

PMID- 24887839
TI  - Obstructive bioprosthetic mitral valve thrombus: management options?
AB  - Bioprosthetic valve thrombosis is an extremely rare event, therefore, long-term
      anticoagulation can be avoided. There is limited experience in the diagnosis and
      treatment of such a situation. We present the case of a patient with a porcine
      mitral bioprosthesis who presented with acute pulmonary edema, likely secondary
      to obstructive valve thrombosis. A favorable outcome was observed after
      conservative anticoagulant treatment. 

PMID- 24887840
TI  - Bilateral central vein stenosis in a dialysis patient with a pacemaker.
AB  - Central vein stenosis is not uncommon in hemodialysis-dependent patients as a
      result of mechanical damage to the vessel walls from prior cannulation. It can
      cause ipsilateral upper limb swelling and pain, resulting in suboptimal
      hemodialysis. It is unfortunate for bilateral central vein stenosis to develop
      concomitantly, and rare in the setting of an in-situ pacemaker. This case
      illustrates the successful ligation of a nondependent left arteriovenous fistula
      and stenting of the right subclavian vein with functioning ipsilateral
      arteriovenous fistula, to overcome the problem of symptomatic bilateral upper
      limb swelling. 

PMID- 24887841
TI  - Use of Foley catheter for insertion of ventricular assist device inflow cannula.
AB  - Ventricular assist devices are fast becoming an accepted alternative to treat end
      stage heart failure, and are being implemented as a bridge to myocardial
      recovery, a bridge to heart transplantation, or as destination therapy.
      Positioning of the inflow cannula into the apex of the ventricle is a crucial
      step due to the risk of sucking in air. We describe an improved method of
      preparing the insertion site for the ventricular assist device inflow cannula, to
      minimize the chances of air embolism and blood spillage, which we applied in a 34
      year-old man, as a bridge to transplantation. 

PMID- 24887842
TI  - Intralobar pulmonary sequestration fed from aortic aneurysm.

PMID- 24887843
TI  - Unusual case of chondroblastic osteosarcoma of the rib in an adult.
AB  - Primary osteosarcoma arising from the ribs is very rare. An unusual case of a
      primary chondroblastic osteosarcoma of the rib in a 30-year-old woman is
      described here. The patient underwent wide excision of the tumor along with the
      involved rib, followed by chemotherapy. Although clinically unsuspected in this
      unusual site, pathology confirmed a completely resected chondroblastic
      osteosarcoma. 

PMID- 24887844
TI  - Aneurysmal superior vena cava in a new born.

PMID- 24887845
TI  - Aspergillus infection in pulmonary cavitating lesions with right atrial myxoma.
AB  - Cardiac myxomas are rare primary tumors with varied clinical presentations that
      may pose a diagnostic challenge. Here, we describe the case of a 21-year-old man
      with multiple cavitating lung lesions with aspergillosis and underlying right
      atrial myxoma, who presented with hemoptysis and weight loss. He was successfully
      treated with right atrial myxoma resection and antifungal agents, with no
      recurrence or complications after one year of follow-up. 

PMID- 24887846
TI  - Hybrid debranching endovascular aortic repair with coronary artery bypass.

PMID- 24887847
TI  - Surgical approach to huge cardiac hydatid cyst of the interventricular septum.
AB  - Cardiac echinococcosis is a rare but potentially fatal condition. The cysts are
      frequently located in the left or right ventricle; involvement of the
      interventricular septum is exceptional. We report the case of a 29-year-old woman
      who presented with palpitation and generalized T-wave inversion on her
      electrocardiogram. Transthoracic echocardiography, magnetic resonance imaging,
      and contrast-enhanced computed tomography showed a huge hydatid cyst originating
      from the interventricular septum. She was started on albendazole tablets, and
      surgical excision on cardiopulmonary bypass was carried out after 5 days of
      treatment. She had an uneventful postoperative recovery, and was continued on
      albendazole tablets for 4 months. 

PMID- 24887849
TI  - Aortic dissection one year after aortic valve replacement.
AB  - Acute aortic dissection after aortic valve replacement is rare. A 57-year-old man
      presented with an acute type A aortic dissection 1 year after aortic valve
      replacement, which originated from the previous aortotomy site. He underwent a
      Bentall procedure. Postoperatively, he developed complete heart block requiring
      permanent pacemaker implantation. During aortic valve replacement, risk factors
      for aortic dissection (diameter of the aorta and fragility and thinness of the
      aortic wall) should be assessed. Prophylactic aortic root replacement should be
      undertaken if the aortic root is more than 45 mm in diameter. 

PMID- 24887848
TI  - Catastrophic complication following heparin therapy.
AB  - Heparin-induced thrombocytopenia is a rare but serious and life-threatening
      complication of heparin use. We describe the case of a 7-year-old girl with
      tetralogy of Fallot with pulmonary atresia, who developed multiple thrombotic
      complications following intracardiac repair, requiring below elbow amputation of
      the left forearm and right forefoot. Our case illustrates the need for greater
      awareness of heparin-induced thrombocytopenia, to prevent the significant
      morbidity associated with it. 

PMID- 24887850
TI  - Surgical treatment of systemic embolization by cardiac metastasis of lung cancer.
AB  - Pulmonary vein infiltration from a malignant lung neoplasm is a serious condition
      that may result in a constant source of systemic emboli. Although surgery is
      often indicated to prevent recurrent embolism, aggressive approaches have shown a
      high rate of perioperative morbidity. We herein report the case of a patient
      diagnosed with lung cancer infiltrating the cardiac chambers through the left
      superior pulmonary vein, who was treated by left pulmonary vein patch closure as
      a preventive and less invasive measure to reduce the thromboembolic risk. 

PMID- 24887851
TI  - Devised reinforcement of distal stump in total arch replacement using BioGlue.
AB  - Although thoracic endovascular aortic repair and the open stent-grafting
      technique have become popular, surgical replacement of the aorta remains the
      procedure of choice for arch aneurysms. Distal anastomosis in total arch
      replacement is fraught with danger in the patient with a fragile aortic wall, and
      can lead to uncontrollable bleeding from the fragile distal stump with existing
      reinforcement techniques. We describe an easy and secure distal anastomosis
      reinforcement technique, the "BioGlue rolled sandwich technique", for total arch
      replacement, which avoids the difficulties of application of BioGlue near the
      vagus and phrenic nerves. 

PMID- 24887852
TI  - Aspergilloma in a pneumonectomized cavity.

PMID- 24887853
TI  - Late relapse of multiple myeloma presenting as a right atrial mass.
AB  - Intracardiac involvement is a rare presentation of relapsed multiple myeloma. We
      present a case of lobulated mass in the wall of the right atrium, with extension
      to the inferior vena cava and obliteration and encasement of the interatrial
      septum in a 57-year-old man, a known case of multiple myeloma, with progressive
      exertional dyspnea and anasarca. 

PMID- 24887854
TI  - Triple synchronous primary lung cancer.
AB  - Synchronous multiple primary lung cancer is rare and difficult to differentiate
      from metastatic disease. State-of-the-art diagnostic tools may contribute to
      discern synchronous multiple primary lung cancer from lung cancer or other
      primary tumors with pulmonary metastases, thus allowing implementation of
      curative strategies. We report the case of a 72-year-old woman with 3 synchronous
      primary lung cancers. 

PMID- 24887855
TI  - Total anomalous systemic and pulmonary venous connection.
AB  - Total anomalous systemic and pulmonary venous connection is an extremely rare
      congenital cardiac anomaly. We present our unique experience of managing this
      complex partially diagnosed cardiac anomaly in a 16-month-old boy. The systemic
      venous anomaly was not detected during the initial preoperative evaluation. He
      was doing well on follow-up, with normal pulmonary artery pressure. 

PMID- 24887856
TI  - Ascending necrotizing mediastinitis secondary to emphysematous pyelonephritis.
AB  - Mediastinal infections usually originate from postoperative complications or in a
      descending manner from a cervical infectious process; few reports have emerged
      describing an ascending trajectory. A 56-year-old woman with a Huang class 1 left
      emphysematous pyelonephritis was referred due to a progression of an ascending
      necrotizing mediastinitis. A left posterolateral thoracotomy was performed,
      drainage and thorough lavage were carried out with a successful outcome. We
      believe this is the first reported case of ascending necrotizing mediastinitis
      secondary to an emphysematous renal infection. 

PMID- 24887857
TI  - Intramedullary cervical abscess in the setting of aortic valve endocarditis.
AB  - Spinal cord tissue has a remarkable resistance to infection. An intramedullary
      abscess is an exceptional complication of infective endocarditis in the post
      antibiotic era. We describe the case of a 42-year-old man who presented with
      fever and cephalea. Two days later, left-side numbness, lack of sphincter
      control, and a new aortic murmur were noticed. Magnetic resonance imaging
      demonstrated an 8 *15-mm intramedullary cervical abscess. Transesophageal
      echocardiography revealed an aortic valve perforation as a result of infective
      endocarditis. Conservative management was decided for the intramedullary abscess.

PMID- 24887858
TI  - Chest wall reconstruction in Marfan syndrome following aortic root replacement.
AB  - Chest wall and spine deformities are common in Marfan syndrome, and often coexist
      with cardiac defects. Surgery is often needed to both the aortic root and the
      anterior chest wall, and early spinal surgery is not uncommon. We describe a case
      of severe thoracic cage deformity with aortic root dilatation, which was managed
      by a staged approach, with a very good final result. 

PMID- 24887859
TI  - A case of extreme upper limb surgical revascularization in Buerger's disease.
AB  - Thromboangiitis obliterans or Buerger's disease is a rare nonatherosclerotic
      segmental inflammatory vasculitis that most commonly involves small and medium
      sized arteries, veins, and nerves of the extremities, and generally affects young
      tobacco smokers. A 51-year-old man was found to have critical ischemia of his
      left hand, with necrosis of 3 fingers. He underwent extremely distal surgical
      revascularization using a cephalic vein bypass graft. 

PMID- 24887860
TI  - A novel modified Robicsek technique for sternal closure: "Double-check".
AB  - A median sternotomy is the most common approach for cardiac and great vessel
      surgery. After a median sternotomy, healing complications such as instability,
      nonunion, and infection, are rare but devastating. Predisposing factors for
      sternal complications are old age, diabetes, steroid treatment, postmenopause
      state, obesity, reoperation, and the use of bilateral internal mammary arteries.
      Patients with sternal dehiscence frequently require reoperation to maintain
      optimum sternal stability. The technique chosen for sternal closure must provide
      excellent sternal approximation. We describe a modified Robicsek procedure
      reinforced with figure-of-8 sternal wires. We named this technique "double
      check". 

PMID- 24887861
TI  - Giant osteosarcoma of chest wall requiring resection and pneumonectomy.
AB  - We present the case of a 13-year-old girl who had a large swelling in her left
      breast with a history of weight loss, low-grade fever, and cold sweats. Computed
      tomography showed a large mass encroaching on the mediastinum and heart, with
      erosion of the adjacent ribs. Resection of the mass along with a pneumonectomy
      were performed. Postoperative tests showed no sign of metastases. 

PMID- 24887862
TI  - Malignant transformation in solitary fibrous tumor of the pleura.
AB  - A 55-year-old man with a solitary fibrous tumor of the pleura on the left side
      underwent resection, but 2 recurrent tumors were found 3 years later. The
      recurrent tumors were reported to have undergone malignant transformation.
      Recurrent solitary fibrous tumor of the pleura with malignant progression is
      rare. Solitary fibrous tumor of the pleura often has an indolent clinical course,
      and may be asymptomatic for several years, so postoperative surveillance may
      necessitate long-term follow-up because of the potentially malignant
      transformative biological behavior of this type of tumor. 

PMID- 24887863
TI  - Coronary-cameral fistula masquerading as a ventricular septal defect.

PMID- 24887864
TI  - Devised loop-in-loop technique in mitral valve repair.
AB  - The loop technique is useful for multiple chordal reconstructions in mitral valve
      repair. Although it is easy to anchor the loop to the tip of the prolapsed
      leaflet, take-down of the anchored loop is not easy. The devised loop-in-loop
      technique makes intraoperative adjustment of the neochordae quick and easy. This
      article describes a straightforward and reproducible method for secure anchoring
      and, if necessary, take-down of neochordae using the loop-in-loop technique for
      mitral valve repair. 

PMID- 24887865
TI  - Coronary bypass using bilateral internal mammary arteries in an achondroplast.
AB  - Coronary bypass grafting for ischemic heart disease in achondroplastic dwarfs is
      very rare. Shortage of veins and inadequate vein quality may cause difficulties
      during surgery. Only 2 cases of coronary bypass surgery in an achondroplastic
      dwarf, in which the left internal mammary artery and vein grafts were used, have
      been reported. We describe the case of a 55-year-old male achondroplastic dwarf
      who had triple-vessel coronary disease and underwent successful coronary bypass
      surgery using one saphenous vein graft and bilateral internal mammary artery
      grafts. The anatomic and surgical challenges in achondroplasia are highlighted. 

PMID- 24887866
TI  - Congenital complex tracheal deformity associated with heart disease in an infant.

PMID- 24887867
TI  - Pulmonary atresia with left main coronary artery fistula to the pulmonary artery.

PMID- 24887868
TI  - Percutaneous closure of atrial septal defect with situs solitus and dextrocardia.
AB  - Percutaneous closure of secundum atrial septal defect associated with situs
      solitus and dextrocardia has not been reported previously. We describe the
      technical difficulties encountered during transcatheter closure of a secundum
      atrial septal defect in a 19-month-old girl with situs solitus and dextrocardia. 

PMID- 24887869
TI  - Delayed surgery for type A aortic dissection caused by blunt trauma.
AB  - We describe a rare case of delayed surgery for blunt ascending aortic injury. A
      77-year-old man was injured in a traffic accident. He lost consciousness and
      suffered severe blunt trauma to the chest. Computed tomography showed multiple
      head and chest injuries and acute Stanford type A aortic dissection. The
      operation was postponed because he was hemodynamically stable and his risk of
      surgical death was increased due to his other injuries. Serial computed
      tomography showed growth of the aortic lesion, and aortic surgery was
      successfully performed 11 months after admission to the hospital. The
      postoperative course was uneventful. 

PMID- 24887870
TI  - Cardiac rupture due to blunt chest trauma: postmortem findings in two cases.

PMID- 24887871
TI  - Aortic root replacement with absent left-main coronary artery: how to do it.
AB  - Aortic root replacement in patient with a coronary artery anomaly can be
      challenging. We describe aortic root replacement in a patient with annuloaortic
      ectasia and coarctation, who had an absent left main coronary artery. There were
      separate origins of the left anterior descending and left circumflex coronary
      arteries from the aorta. The technical modification employed in this case is
      discussed. 

PMID- 24887872
TI  - Sinus node dysfunction complicating viper bite.
AB  - Viper venom toxicities comprise mainly bleeding disorders and nephrotoxicity.
      Cardiotoxicity is a rare manifestation of viper bite. We describe the case of a
      previously healthy 35-year-old man who developed coagulopathy and sinus node
      dysfunction following a viper bite. Electrocardiography showed sinus arrest and
      junctional escape rhythm. This is the first account of sinus node dysfunction
      caused by a viper bite. 

PMID- 24887873
TI  - Carotid-esophageal fistula due to a retained foreign body.
AB  - We describe a case of carotid-esophageal fistula due to retention of an ingested
      foreign body in a 65-year-old woman. Late diagnosis resulted in severe hemorrhage
      and postoperative cerebrovascular accident because of the impossibility of
      repairing the carotid artery due to severe local inflammation. 

PMID- 24887874
TI  - Clinical and echocardiographic predicators of postoperative atrial fibrillation.
AB  - BACKGROUND: Postoperative atrial fibrillation is the most common arrhythmia after
      coronary artery bypass grafting, with a reported incidence of 10% to 60%.
      Preoperative clinical and echocardiographic data, especially the atrial
      electromechanical interval, predict postoperative atrial fibrillation in elective
      coronary artery bypass patients. METHODS: A prospective study evaluated
      preoperative clinical and echocardiographic data in 192 patients who underwent
      elective coronary artery bypass from 2010 to 2012. RESULTS: 18 (9.37%) patients
      developed postoperative atrial fibrillation. Compared to patients without
      postoperative atrial fibrillation, these 18 had significantly longer intensive
      care unit and hospital stays, they were significantly older (58.62 +/- 10.02 vs.
      53.22 +/- 8.23 years; p = 0.02), with a larger left atrial volume (83.39 +/- 8.31
      vs. 55.47 +/- 8.37 cm(3), p = 0.001), longer atrial electromechanical interval
      (133.67 +/- 8.15 vs. 98.05 +/- 6.71 ms p < 0.0001), and lower tissue Doppler
      imaging systolic velocity wave amplitude (6.6 +/- 1 vs. 9.4 +/- 2.2 cm.s(-1); p =
      0.001); they also had a higher prevalence of hypertension (61.11% vs. 38.5%; p =
      0.04). Using 115 ms as the cutoff value of atrial electromechanical interval
      enabled us to detect patients who developed postoperative atrial fibrillation
      with 100% sensitivity, 77% specificity, 78% positive predictive value, and 100%
      negative predictive value. CONCLUSION: Older hypertensive patients are at higher
      risk of developing postoperative atrial fibrillation. Preoperative measurement of
      atrial electromechanical interval by tissue Doppler echocardiography is a useful
      predictor of postoperative atrial fibrillation in coronary artery bypass
      patients.

PMID- 24887875
TI  - Acute coronary syndrome in two patients with mechanical valve prostheses.
AB  - We report 2 similar cases of embolic myocardial infarction due to thrombus on a
      mechanical prosthesis despite anticoagulation therapy. In our first case,
      aspiration of the thrombus was performed successfully. Our second patient was
      given medical treatment with target international normalized ratio values between
      3.5 and 4.0. 

PMID- 24887876
TI  - Pulmonary artery banding for univentricular heart beyond the neonatal period.
AB  - BACKGROUND: It is standard practice to band the pulmonary artery at 2 to 4 weeks
      of age in patients with univentricular hearts with increased pulmonary blood
      flow. The behavior of patients banded beyond the neonatal period has not been
      well elucidated. PATIENTS AND METHODS: This was a retrospective chart review of
      32 consecutive patients (one neonate) who underwent pulmonary artery banding for
      functionally univentricular heart. The mean age at banding was 5.7 +/- 6.0
      months, and 34.4% were over 6-months old. RESULTS: Mortality was 15.6%. The mean
      systolic pulmonary artery pressure decreased from 43.6 +/- 9.7 to 29.6 +/- 7.0 mm
      Hg. The mean pre-discharge echocardiographic band gradient was 60.6 +/- 13.6 mm
      Hg (mean systemic systolic pressure 73.7 +/- 11.0 mm Hg) and systemic oxygen
      saturation was 81.7% +/- 5.8%. At a mean follow-up period of 44.9 +/- 30.0
      months, 6 patients were lost to follow-up, 13 had undergone bidirectional Glenn
      shunt, and 7 had Fontan operations. Pulmonary artery mean pressure was 17.2 +/-
      4.6 mm Hg at pre-Glenn catheterization. Of the 5 patients who had not undergone
      further surgery, only one was inoperable. All were in functional class I or II.
      CONCLUSION: Pulmonary artery banding beyond the neonatal period in suitable
      patients with univentricular hearts provides reasonable palliation in the
      intermediate term, with a significant number successfully undergoing Fontan
      stages.

PMID- 24887877
TI  - Double aortic arch and Kommerell's diverticulum.

PMID- 24887878
TI  - Management of a rare gastrobronchial fistula following recurrent pancreatitis.
AB  - A 41-year-old male smoker presented with choking and coughing up food associated
      with repeated vomiting. Four years previously, following recurrent episodes of
      pancreatitis, he required percutaneous necrosectomy. He subsequently had a
      cholecystectomy and mesh repair of the abdominal wall, and later developed
      multiple problems including a gastrobronchial fistula. Computed tomography
      revealed a fistulous connection for which he had a combined procedure. Through a
      thoracolaparotomy approach, the left lower lobe and fistulous connection were
      removed along with the surrounding diaphragm and the associated fundus of the
      stomach. The diaphragm defect was repaired without mesh. 

PMID- 24887879
TI  - Systematic review of spontaneous pneumomediastinum: a survey of 22 years' data.
AB  - OBJECTIVE: To describe and clarify management protocols in relation to
      spontaneous pneumomediastinum, and try to integrate criteria on this subject.
      BACKGROUND: Thoracic physicians are faced with patients who present with gas in
      the mediastinum, frequently without an obvious etiologic factor. Published
      material contains heterogeneous information from which different conclusions can
      be drawn. METHODS: In a Medline search from 1990 to 2012, we collected data on
      mortality, morbidity, signs, symptoms, etiologic factors, and diagnostic methods.
      Standardized mean differences were calculated. RESULTS: We identified 600
      patients in 27 papers with series of >5 patients without precipitating or
      etiologic factors previous to the clinical presentation, but athletic activity,
      drug abuse, and history of asthma played an apparent role in the disease process.
      Most patients complained of thoracic pain and dyspnea, with subcutaneous
      emphysema and Hamman's sign. The most common complication was tension
      pneumothorax. Morbidity was seen in 2.8%; no mortality has been reported so far.
      CONCLUSION: Spontaneous pneumomediastinum is a rare disease with a benign course,
      which should be treated conservatively unless a complication mandates an invasive
      procedure. An algorithm for diagnosis and treatment is offered, based on the
      available evidence.

PMID- 24887880
TI  - Effect of body mass index on early clinical outcomes after cardiac surgery.
AB  - BACKGROUND: there are several reports on the outcomes of cardiac surgery in
      relation to body mass index. Some concluded that obesity did not increase
      morbidity or mortality after cardiac surgery, whereas others demonstrated that
      obesity was a predictor of both morbidity and mortality. METHODS: this was a
      retrospective study of 3370 adult patients undergoing cardiac surgery. The
      patients were divided into 4 groups according to body mass index. The 4 groups
      were compared in terms of preoperative, operative, and postoperative
      characteristics. RESULTS: obese patients had a significantly younger mean age.
      Diabetes, hypertension, and hyperlipidemia were significantly more common in
      obese patients. The crossclamp time was significantly longer in the underweight
      group. Reoperation for bleeding, and pulmonary, gastrointestinal, and renal
      complications were significantly more common in the underweight group. Wound
      complications were significantly more frequent in the obese group. Mortality was
      inversely proportional to body mass index. The adjusted odds ratios of the early
      clinical outcomes demonstrated a higher risk of wound complications in overweight
      and obese patients CONCLUSION: body mass index has no effect on early clinical
      outcomes after cardiac surgery, except for a higher risk of wound complications
      in overweight and obese patients.

PMID- 24887881
TI  - Reduced left internal mammary artery blood flow on normal sternal retraction.
AB  - The left internal mammary artery is the conduit of choice for bypassing the left
      anterior descending artery. A 72-year-old man underwent off-pump triple-vessel
      coronary artery bypass. The left internal mammary artery was harvested with brisk
      blood flow from the distal artery on completion of harvesting, but normal sternal
      retraction with a Medtronic OctoBase retractor led to cessation of flow. A vein
      graft was utilized for the left anterior descending artery, and the internal
      mammary artery was grafted to the first diagonal branch. Computed tomography
      angiography on postoperative day 5 demonstrated no possible cause of the reduced
      flow on sternal retraction. 

PMID- 24887883
TI  - Double aortic arch determining tracheal stenosis in an adult: erratum.

PMID- 24887882
TI  - Differential release kinetics of cardiac biomarkers in off-pump coronary bypass.
AB  - BACKGROUND: Differential release kinetics of the cardiac biomarkers (B-type
      natriuretic peptide, troponin I, and creatine kinase-MB) following off-pump
      coronary artery bypass are not well characterized. METHODS: Biomarker levels were
      assessed at 6, 24, 48 h, and 1 month preoperatively, in 80 patients who underwent
      off-pump coronary artery bypass. RESULTS: All biomarkers increased within 6 h of
      surgery. Peak B-type natriuretic peptide levels occurred at 24-48 h in 96% of
      patients, but only two-thirds had peak troponin I and creatine kinase-MB levels
      at this time, reflecting different release patterns. Levels of all biomarkers
      declined within 48 h, but 42% of patients still had B-type natriuretic peptide
      >100 pg.mL(-1) at 1 month. Those with baseline B-type natriuretic peptide > 100
      pg.mL(-1) had a lower left ventricular ejection fraction (43.6% vs. 55.6%, p <
      0.01) and longer inotropic (43.8 vs. 31.4 h, p = 0.03) and ventilator support (34
      vs. 25.5 h, p = 0.04) than those with lower levels. B-type natriuretic peptide
      levels correlated positively with angiographic Syntax score (p = 0.02) and
      negatively with left ventricular ejection fraction (p < 0.001). Only baseline B
      type natriuretic peptide predicted the durations of inotropic support (p = 0.01)
      and ventilation (p = 0.02). Postoperative B-type natriuretic peptide at 6, 24,
      and 48 h and delta B-type natriuretic peptide were significant predictors of mean
      ventilation time. CONCLUSION: Even in patients undergoing off-pump surgery, there
      is significant natriuretic peptide and myocardial enzyme release. Only B-type
      natriuretic peptide levels had an association with postoperative variables.

PMID- 24887885
TI  - Anomalous drainage of a persistent left superior vena cava into the left atrium.

PMID- 24887884
TI  - Thymoma type B1 arising in a giant supradiaphragmatic thymolipoma.
AB  - Thymolipomas are uncommon tumors of the anterior mediastinum. They may extend
      into, but rarely stem from, the chest cavity. Furthermore, thymoma arising in a
      thymolipoma is extremely rare. We report a unique case of thymoma type B1 that
      originated form a giant thymolipoma located in the chest cavity, which was
      resected by a lateral thoracotomy in a 23-year-old woman. To our knowledge, this
      is the first reported case of thymoma type B1 arising within a giant thymolipoma.

PMID- 24887887
TI  - Surgical repair of unroofed coronary sinus atrial septal defect in an adult.

PMID- 24887886
TI  - Thoracic liposarcoma: resection and chest wall reconstruction.
AB  - Liposarcoma is a malignant neoplasm of mesodermal origin derived from adipose
      tissue. It most often originates in the extremities and retroperitoneum, and less
      frequently in the head and neck. Liposarcoma involving the chest wall is
      extremely rare with few reported cases. Surgery is the mainstay of treatment, and
      complete resection is the major factor influencing survival. We describe the case
      of a 65-year-old man diagnosed with a dedifferentiated liposarcoma of the chest
      wall, who underwent radical resection and chest wall reconstruction with a
      latissimus dorsi musculocutaneous flap. 

PMID- 24887888
TI  - Esophageal perforation after radiofrequency ablation for atrial fibrillation.
AB  - A 69-year-old man underwent left atrial radiofrequency ablation for atrial
      fibrillation. After 10 minutes, the procedure was terminated due to pericardial
      tamponade secondary to perforation during mapping. Pericardiocentesis resolved
      the tamponade. Ablation was completed one week later, and the patient was
      discharged. Two days later, he presented with odynophagia. Computed tomography
      demonstrated small bilateral pleural effusions. He was judged to be stable and
      was discharged again, but returned 2 days later with chest pain. He was found to
      have esophageal perforation with empyema, which was repaired using a muscle patch
      and esophageal stenting, successfully treating the lesion with minimal morbidity.

PMID- 24887889
TI  - Giant right atrial diverticulum with thrombus formation.
AB  - A 28-year-old man was referred to our hospital with a giant right atrial
      diverticulum. The mass of the right atrial diverticulum compressed the right
      atrium and right ventricle, and thrombus formation was suspected. The
      diverticulum was surgically excised and the patient remained asymptomatic a year
      later. 

PMID- 24887890
TI  - Giant right atrial lipoma mimicking tamponade.
AB  - Cardiac lipomas are rarely encountered. They are mostly asymptomatic and may be
      discovered incidentally. We describe the case of a 56 year-old man with a
      presentation similar to tamponade. He had decreased heart sounds, global
      cardiomegaly, and oligemic lung fields. Echocardiography showed a 110 * 75-mm
      mass attached to the interatrial septum, almost completely occupying the right
      atrium. Chest computed tomography showed a large homogeneous low-attenuation mass
      with thin septa, originating from interatrial septum and filling the right
      atrium, consistent with lipoma. The patient underwent surgery for resection of
      the tumor. Pathologic examination was consistent with cardiac lipoma. 

PMID- 24887891
TI  - Surgical outcome of Fontan conversion and arrhythmia surgery: Need a pacemaker?
AB  - BACKGROUND: Atrial tachyarrhythmias are frequent complications in the late period
      after the Fontan procedure, and important risk factors for a poor prognosis. The
      impact of Fontan conversion and arrhythmia surgery in failed Fontan patients has
      been described in many reports. OBJECTIVE: We evaluated our experience with
      Fontan conversion procedures, concomitant arrhythmia surgery, and pacemaker
      implantation. METHODS: We reviewed the hospital records of 25 consecutive
      patients who underwent a Fontan conversion procedure from January 2004 to March
      2012. Twenty-four patients had arrhythmia surgery using cryoablation and
      radiofrequency ablation at the time of conversion. A bilateral atrial maze
      procedure was performed in 6 patients, right-side maze in 15, and isthmus block
      in 3. Three patients with a diagnosis of corrected transposition of the great
      arteries underwent simultaneous pacemaker implantation electively. RESULTS: There
      was no early death and one late death during a mean follow-up period of 21.2
      months. Three tachyarrhythmia recurrences developed, and there were 4 occurrences
      of sinus bradycardia. Five of these patients required postoperative pacemaker
      implantation. CONCLUSION: The mid-term results of Fontan conversion and
      arrhythmia surgery in our institute were satisfactory. The occurrence of
      unexpected postoperative pacemaker requirement was high in the patients who
      underwent a right atrial or bilateral atrial maze procedure. Pacemaker or lead
      implantation is recommended for patients planned to undergo a right-side or full
      maze procedure.

PMID- 24887892
TI  - Coronary-pulmonary artery fistula in tetralogy of Fallot with pulmonary atresia.
AB  - Surgical correction of patients with tetralogy of Fallot with pulmonary atresia
      is now one of the routine procedures performed by pediatric cardiac surgeons. In
      one variant, the pulmonary arterial supply is derived from a fistulous
      communication from the coronary arteries. This rare and interesting situation
      poses a diagnostic and therapeutic dilemma, as well as providing specific
      management challenges to the surgical team. Here, we discuss important aspects of
      this rare variant, specifically its morphology, presentation, evaluation and
      management. 

PMID- 24887893
TI  - Disease of the internal mammary artery: rare or undiagnosed?

PMID- 24887894
TI  - Video-assisted mediastinoscopic resection of mediastinal cyst (lymphangioma).
AB  - Mediastinal cysts account for 20% of all mediastinal masses. Symptomatic cysts
      need treatment, and surgical excision is the treatment of choice. One approach to
      resect them is video-assisted mediastinoscopy. An 80-year-old man with cough and
      dyspnea at rest was referred for evaluation. Chest computed tomography revealed a
      mediastinal cyst. Because of his symptoms, he was a candidate for surgery, and
      the cyst was resected by video-assisted mediastinoscopy through a cervical
      incision. Video-assisted mediastinoscopy is a safe and effective approach for
      complete resection of mediastinal cysts. 

PMID- 24887895
TI  - Hydatid cyst of the cardiac interventricular septum.
AB  - Hydatid cysts of the cardiac interventricular septum are rare and present a
      diagnostic and therapeutic challenge. We report the case of a 48-year-old woman
      who was successfully treated with cyst excision and capitonnage. 

PMID- 24887896
TI  - The outcome of surgical management of type A aortic dissection.
AB  - BACKGROUND: Type A aortic dissection is a serious and fatal condition. METHODS:
      We retrospectively evaluated the outcome following repair of ascending aortic
      dissection in a contemporary cohort of 108 patients with a mean age of 59.5 +/-
      13.8 years, who were treated between 2006 and 2011. Most patients were male (70,
      65%). RESULTS: Circulatory arrest with a mean duration of 22 +/- 16 min was
      performed in 42 (38.9%) patients. Perioperative mortality was 15.7% (n = 17).
      Univariate analysis showed that cardiopulmonary bypass time (p = 0.0006), age >60
      years (p = 0.028), cardiogenic shock at presentation (p = 0.02), New York Heart
      Association class II-IV (p = 0.038), hemopericardium (p = 0.0035), and
      preoperative cerebrovascular accident (p = 0.02) were predictors of mortality.
      Multivariate analysis indicated that age >60 years (odds ratio 7.7, 95%
      confidence interval: 1.52-38.96, p = 0.0136), preoperative cerebrovascular
      accident (odds ratio 25.2, 95% confidence interval: 2.45-258.9, p = 0.0066),
      hemopericardium (odds ratio 41.6, 95% confidence interval: 5.38-320.7, p =
      0.0003), and cardiopulmonary bypass time (odds ratio 1.85, 95% confidence
      interval: 1.32-2.57, p = 0.0003) were independent predictors of perioperative
      mortality. The 1- and 4-year survival was 80% +/- 3.8% and 69% +/- 5.7%,
      respectively. Age >60 years (hazard ratio 3.3, 95% confidence interval: 1.4-7.9,
      p = 0.0064) was the only independent predictor of long-term mortality.
      CONCLUSION: Our results identify the major risk factors for perioperative and
      long-term mortality. Age is an independent risk factor for mortality.

PMID- 24887899
TI  - A giant bulla causing heart disappearance in a small infant.

PMID- 24887898
TI  - Open heart surgery after renal transplantation.
AB  - AIM: to evaluate the strategy for open heart surgery after renal transplantation
      performed in a single institution in Japan. METHODS: we reviewed 6 open heart
      surgeries after renal transplantation in 5 patients, performed between January
      1992 and December 2012. The patients were 3 men and 2 women with a mean age of 60
      +/- 11 years (range 46-68 years). They had old myocardial infarction and unstable
      angina, aortic and mitral stenosis, left arterial myxoma, aortic stenosis, and
      native valve endocarditis followed by prosthetic valve endocarditis. Operative
      procedures included coronary artery bypass grafting, double-valve replacement,
      resection of left arterial myxoma, 2 aortic valve replacements, and a double
      valve replacement. Renal protection consisted of steroid cover (hydrocortisone
      100-500 mg or methylprednisolone 1000 mg) and intravenous immunosuppressant
      infusion (cyclosporine 30-40 mg day(-1) or tacrolimus 1.0 mg day(-1)). RESULTS: 5
      cases were uneventful and good renal graft function was maintained at discharge
      (serum creatinine 2.1 +/- 0.5 mg dL(-1)). There was one operative death after
      emergency double-valve replacement for methicillin-resistant Staphylococcus
      aureus-associated prosthetic valve endocarditis. Although the endocarditis
      improved after valve replacement, the patient died of postoperative pneumonia on
      postoperative day 45. CONCLUSIONS: careful perioperative management can allow
      successful open heart surgery after renal transplantation. However, severe
      complications, especially methicillin-resistant Staphylococcus aureus infection,
      may cause renal graft loss.

PMID- 24887897
TI  - Patient-controlled analgesia after coronary bypass: Remifentanil or sufentanil?
AB  - BACKGROUND: adequate pain control after cardiac surgery is mandatory to reduce
      its remarkable morbidity. In this study, we aimed to compare the efficacy of
      patient-controlled analgesia with remifentanil or sufentanil for pain management
      after coronary artery bypass grafting. METHODS: 249 patients who underwent
      coronary artery bypass were randomly assigned to receive patient-controlled
      analgesia with remifentanil or sufentanil during the first 24 h postoperatively.
      Pain intensity during patient-controlled analgesia was assessed using 4 different
      pain rating scales. RESULTS: patients given remifentanil had lower Visual Analog
      Scale scores at 24 h compared to those given sufentanil (p = 0.002). The Numeric
      Rating Scale at 24 h was also significantly lower in patients using remifentanil
      (p = 0.004). The Faces Pain Scale scores at 4, 18, and 24 h were significantly
      lower in patients using remifentanil compared to those using sufentanil (p =
      0.045, 0.036, and 0.011, respectively). No significant differences between groups
      were seen in the pain intensity assessed by the Behavior Rating Scale at any time
      point during the first 24 h postoperatively. CONCLUSION: our study showed that
      both remifentanil and sufentanil patient-controlled analgesia can provide
      acceptable analgesia after coronary artery bypass. The difference between their
      efficacies was inconspicuous until 24 h postoperatively. Remifentanil seems to
      result in better pain relief at 24 h postoperatively.

PMID- 24887900
TI  - Pericardial echinococcosis: unusual presentation in a non-endemic region.

PMID- 24887901
TI  - Unusual combination of cardiac and pulmonary congenital defects in a neonate.

PMID- 24887902
TI  - Bilateral thoracoscopic thymectomy using a novel positioning system.
AB  - Several techniques of bilateral video-assisted thoracoscopic extended thymectomy
      have been proposed, and each has its own proponents. We summarize our experience
      in 20 patients who underwent bilateral video-assisted thoracoscopic extended
      thymectomy, using a new patient positioning that amplifies the thoracoscopic view
      of the cardiophrenic regions which are often difficult to visualize with standard
      techniques. In all cases, en-bloc thymectomy with complete dissection of the
      mediastinal fatty tissue was achieved without sternal retractors or additional
      incisions. 

PMID- 24887903
TI  - Giant solitary fibrous tumor of the pleura.
AB  - Solitary fibrous tumors are rare mesenchymal tumors accounting for <5% of all
      neoplasms in the pleura and other sites. A 45-year-old man reported to us with
      cough and dyspnea. Radiological investigations revealed a giant mass displacing
      the mediastinum to the left. The tumor weighing 3.0 kg was successfully resected
      via a right thoracotomy. Histology and immunohistochemistry confirmed a benign
      tumor. Recurrence and malignant transformation of these benign tumors have been
      reported. Our patient has been followed up for 4 years with no recurrence. 

PMID- 24887904
TI  - Unusual cause of absent pulse in one arm: Isolated subclavian artery.
AB  - Isolated origin of the subclavian artery is a congenital anomaly of the aortic
      arch in which one subclavian artery originates from the homolateral pulmonary
      artery through the ductus arteriosus. Isolated right subclavian artery with left
      sided aortic arch is extremely rare. We report a case of isolated right
      subclavian artery from the right pulmonary artery via a right-sided ductus
      arteriosus in a 4-year-old girl. The child presented with subclavian pulmonary
      steal with perfusion of the right arm and lung from the right vertebral and
      carotid arteries. She underwent successful surgical repair. 

PMID- 24887906
TI  - Synchronous hybrid repair for ruptured aneurysm of bovine aortic arch.
AB  - Rupture of an aortic arch aneurysm is a life-threatening emergency with the risk
      of mortality escalating by the hour. We describe the successful hybrid repair of
      a ruptured bovine aortic arch aneurysm in a 75-year-old man, which involved
      aortic arch debranching by ascending aorta-bicarotid bypass followed by relining
      of the aortic lumen with a stent-graft. The procedure was not only lifesaving but
      also resulted in an active gentleman at 2-year follow-up. Considering the
      morbidity and mortality of open surgery using circulatory arrest, state-of-the
      art synchronous hybrid repair seems to be an effective alternative for ruptured
      aortic arch aneurysms. 

PMID- 24887905
TI  - Ring annuloplasty for ischemic mitral regurgitation: a single center experience.
AB  - BACKGROUND: Ischemic mitral regurgitation associated with coronary artery disease
      presents a management challenge to cardiac surgeons. We report our early and
      midterm results of chronic ischemic mitral regurgitation treated with concomitant
      mitral ring annuloplasty and coronary artery bypass grafting. METHODS: We
      performed a retrospective review of the medical records of patients who underwent
      coronary artery bypass grafting at our institute from January 2009 to December
      2011. Data were collected in 50 patients with chronic ischemic mitral
      regurgitation who had mitral ring annuloplasty along with coronary artery bypass
      grafting. Preoperative data, echocardiographic findings, operative procedure,
      outcome, and perioperative hemodynamics were analyzed. Early and intermediate
      follow-up data were also collected and analyzed. RESULTS: There were 3 (6%) early
      and 9 (18%) late deaths. Of the survivors, 38 (76%) had a significant reduction
      in left ventricular end-diastolic and end-systolic dimensions and improvement in
      New York Heart Association functional class. CONCLUSION: Despite a risk of
      residual regurgitation, mitral ring annuloplasty combined with coronary artery
      bypass appears to be a good treatment option in selected patients with chronic
      ischemic mitral regurgitation.

PMID- 24887907
TI  - Morphometric study of the human mitral annulus: guide for mitral valve surgery.
AB  - BACKGROUND: during mitral valve surgery, it is important for surgeons to
      understand the anatomy of the mitral valve annulus to prevent surgical
      complications. This study aimed to perform morphometry of the mitral annulus to
      facilitate secure suturing during ring annuloplasty or replacement of the mitral
      valve. METHODS: an anatomical study was carried out on 7 human hearts. We divided
      the mitral valve annulus into sections containing 8 different points. It was
      noted that the annulus was a complex structure which has fibrous continuity with
      the mitral leaflets, and with or without the aortic annulus. RESULTS: there was
      always a segment of the annular fibrous structure which was facing directly
      toward the left ventricular cavity. The length of the segment ranged from 1.0 to
      3.4 mm. In terms of the size of the annulus, there were large variations within
      the subject and among the subjects. The shortest distance between the mitral
      annulus and left circumflex coronary artery was at the anterolateral commissure,
      and the length was 3.3 mm. CONCLUSION: this study has improved understanding of
      the anatomy of the mitral annulus, which could help surgeons to avoid operative
      complications. Based on this study, several suggestions are made for placing
      sutures for mitral valve replacement and mitral ring annuloplasty.

PMID- 24887908
TI  - Extensive vascular and valvular involvement in Gaucher disease.
AB  - A 17-year-old patient with type III Gaucher disease was hospitalized for
      recurrent syncope. Echocardiography showed calcified aortic and mitral stenosis.
      Three-dimensional computed tomography showed severely calcified plaques on the
      ascending aorta, arcus, and abdominal aorta. On follow-up, palpitations and
      syncope were triggered by emotional stress, followed by severe bradycardia that
      was resulted in cardiogenic shock; the patient died after 8 h despite all
      efforts. Gaucher disease should be kept in mind in the differential diagnosis of
      a young patient with extensive vascular and valvular calcification. Patients with
      symptomatic severe valvular disease must be referred for early surgery.

PMID- 24887909
TI  - Ruptured abdominal aortic aneurysm and aortoiliac vein fistula.
AB  - A 67-year-old man was admitted with severe abdominal pain and back pain. Computed
      tomography showed an infrarenal abdominal aortic aneurysm (8.4 * 8.3 cm) and a
      large retroperitoneal hematoma. Immediately afterwards, the patient suffered
      circulatory collapse and was rushed to the operating theater. A fistula
      communicating with the left iliac vein was found. It was repaired with a Dacron
      patch while balloon-tipped catheters controlled the bleeding. The abdominal
      aortic aneurysm was replaced with a bifurcated graft. The postoperative course
      was uneventful. There have been few reports of successful repair of a ruptured
      abdominal aortic aneurysm associated with aortoiliac arteriovenous fistula.

PMID- 24887910
TI  - Pulmonary vein stenosis in a child with ventricular septal defect.

PMID- 24887911
TI  - A rare case of biventricular outflow obstruction with intact ventricular septum.
AB  - We report a case of pulmonary atresia with intact ventricular septum and aortic
      valve stenosis in a neonate. This combination is extremely rare. Cardiac
      catheterization was performed at 2 days of age, which confirmed the prenatal
      echocardiographic diagnosis and identified associated moderate aortic valve
      stenosis. Soon after the examination, an urgent surgical intervention was
      required due to uncontrollable circulatory instability. The baby underwent a
      successful Fontan-type repair achieved by surgical management only. 

PMID- 24887912
TI  - Attention! Cardiac tamponade may be caused by underlying Castleman's disease.
AB  - Castleman's disease is a rarely observed lymphoproliferative disease. In the
      literature, various signs and symptoms of the disease have been reported; one of
      these is secondary cardiac tamponade. We describe the case of a 41-year-old man
      who developed cardiac tamponade during examination, and who was later diagnosed
      with Castleman's disease, based on his lymph node biopsies. 

PMID- 24887913
TI  - Primary tetralogy of Fallot repair: predictors of intensive care unit morbidity.
AB  - BACKGROUND: Primary repair of tetralogy of Fallot has low surgical mortality, but
      some patients still experience significant postoperative morbidity. Our
      objectives were to review our institutional experience with primary tetralogy of
      Fallot repair, and identify predictors of intensive care unit morbidity. METHODS:
      We reviewed all patients with tetralogy of Fallot who underwent primary repair in
      infancy from 2001 to 2012. Preoperative, operative, and postoperative demographic
      and morphologic data were analyzed. Intensive care unit morbidity was defined as
      prolonged intensive care unit stay (>= 7 days) and/or prolonged duration of
      mechanical ventilation (>= 48 h). RESULTS: 97 patients who underwent primary
      surgical repair during the study period were included in the study. The median
      age was 4.9 months (range 1-9 months) and the median weight was 5.3 kg (range 3.1
      9.8 kg). There was no early surgical mortality. The incidence of junctional
      ectopic tachycardia and persistent complete heart block was 2% and 1%,
      respectively. The median intensive care unit stay was 6 days (range 2-21 days)
      and the median duration of mechanical ventilation was 19 h (range 0-136 h). Age
      and weight were independent predictors of intensive care unit stay, while
      surgical era predicted the duration of mechanical ventilation. CONCLUSION:
      Primary tetralogy of Fallot repair is a safe procedure with low mortality and
      morbidity in a medium-sized program with outcomes comparable to national
      standards. Age and weight at the time of surgery were significant predictors of
      morbidity.

PMID- 24887914
TI  - Aortopulmonary fistula.

PMID- 24887915
TI  - Artifact on postoperative chest radiograph, mimicking retained foreign body.

PMID- 24887916
TI  - A case of left atrial myxoma with unusual tumor vascularity.
AB  - A 69-year-old woman presented with a 2-week history of chest pain and mitral and
      aortic valve replacement 15 and 5 years earlier. Transthoracic echocardiography
      revealed a well-seated monoleaflet mitral valve and a bileaflet aortic valve with
      normal function. Cardiac catheterization showed 3-vessel coronary artery disease
      and an abnormal cluster of new vessels derived from the left atrial circumflex
      and posterior ventricle branches. Two- and 3-dimensional transesophageal
      echocardiography identified a semi-mobile oval left atrial mass with multiple
      internal cystic spaces, attached to the fossa ovalis region in the interatrial
      septum. The mass was resected. The pathological diagnosis was atrial myxoma.

PMID- 24887917
TI  - Iatrogenic foreign body piercing the aorta.

PMID- 24887918
TI  - Blood cyst and stone in an adult heart.

PMID- 24887919
TI  - Postoperative lung hernia resolved by pad compression.

PMID- 24887920
TI  - Delayed tracheal rupture presenting as hoarseness.

PMID- 24887921
TI  - Prior thoracoscopic surgery may improve reoperative pulmonary resection.
AB  - OBJECTIVES: although video-assisted thoracoscopic surgery for pulmonary resection
      appears to be associated with more favorable postoperative outcomes than
      thoracotomy, no reports have discussed its benefit at subsequent reoperative
      pulmonary resection. METHODS: between January 2000 and December 2009, 144
      patients underwent reoperative pulmonary resections for benign and malignant
      nodules at the Mayo Clinic, Rochester. Their data were evaluated retrospectively.
      Twenty-three (16%) patients had prior video-assisted thoracoscopic surgery, and
      121 (84%) had undergone a prior open thoracotomy. Intraoperative and short-term
      postoperative outcomes were analyzed and compared between the two groups, using
      the chi-square test or Mann-Whitney test. RESULTS: overall reoperative mortality
      was 1.38% and morbidity was 49.3%. Intraoperative factor analysis showed that the
      prior video-assisted thoracoscopic surgery group more often underwent anatomical
      resection (p = 0.0011) and showed a tendency towards a lower conversion rate from
      video-assisted thoracoscopic surgery to thoracotomy at reoperative pulmonary
      resection (p = 0.051). Short-term postoperative outcomes showed that the prior
      video-assisted thoracoscopic surgery group had a significantly lower morbidity
      rate (p = 0.013), significantly shorter hospital stay (p = 0.002), and a tendency
      for a shorter duration of chest tube drainage (p = 0.09). CONCLUSION: our results
      suggest that prior video-assisted thoracoscopic surgery may lead to improved
      postoperative outcomes at subsequent reoperative pulmonary resection. Video
      assisted thoracoscopic surgery may be favored for future potential reoperative
      pulmonary resections.

PMID- 24887922
TI  - Intercostal muscle flap and intracostal suture to reduce post-thoracotomy pain.
AB  - BACKGROUND: Thoracotomy is considered to be the most painful surgical access, the
      main culprit being intercostal nerve injury. Despite the use of many techniques,
      this remains a major problem, pointing towards prevention as a better strategy.
      The effect of protecting both the upper and lower intercostal nerves during
      surgery has attracted many researchers. METHOD: A prospective study spanning 15
      months was undertaken in 48 patients randomized to a conventional group (n = 25)
      and a study group (n = 23). Pericostal sutures in the former and intracostal
      sutures in the latter were used for closure. An intercostal muscle flap was
      harvested at the start of the operation in the study group only. The groups were
      comparable in terms of baseline characteristics. With a similar pain protocol,
      pain scores and analgesic consumption were recorded and analyzed. RESULTS: Times
      for pedicle harvest, intracostal suture, and pericostal suture were 5.2 +/- 1.56,
      3.65 +/- 0.71, and 6.4 +/- 1.20 min, respectively, in the study group. Total
      operative time was similar in both groups. Postoperative pain scores and the
      overall frequency of pain were consistently lower in the study group. CONCLUSION:
      these techniques lead to a reduction in the acute and chronic post-thoracotomy
      pain, without increasing complications.

PMID- 24887923
TI  - Multilevel obstruction of left ventricular outflow tract in Shone complex adult.

PMID- 24887924
TI  - Elevated hemoglobin A1c is associated with readmission but not complications.
AB  - BACKGROUND: studies have shown that elevated hemoglobin A1c levels are associated
      with worse short-term outcomes after cardiac surgery. However, the effect on
      readmission has not been studied. The primary purpose of this study was to
      determine the independent effect of hemoglobin A1c level on the readmission rate
      after cardiac surgery. The secondary purpose was assess its effect on
      complications and mortality. METHODS: consecutive patients undergoing coronary
      artery bypass surgery between April 2007 and August 2010 were divided into 3
      groups based on preoperative hemoglobin A1c levels. Outcomes were controlled for
      demographics, comorbidities, and surgery. RESULTS: 300 (34%) patients had normal
      hemoglobin A1c levels (<6.0%), 305 (35%) had mildly elevated levels (6.0%-6.9%),
      and 275 (31%) had markedly elevated levels (>= 7.0%). Postoperative glucose
      levels were similar among all 3 hemoglobin A1c groups. Compared to patients with
      normal hemoglobin A1c levels, those with higher levels were more likely to be
      readmitted: adjusted odds ratio 2.091 (95% confidence interval: 1.074-4.069, p =
      0.036) for hemoglobin A1c 6.1%-6.9%; and adjusted odds ratio 2.089 (95%
      confidence interval: 1.050-4.155, p = 0.036) for hemoglobin A1c >= 7.0. Overall,
      381 (43%) patients suffered complications, and hemoglobin A1c levels were similar
      in those with and without complications (6.8% +/- 1.6% vs. 6.9% +/- 1.7%, p =
      0.837). Mortality was equivalent in all 3 hemoglobin A1c groups. CONCLUSIONS:
      elevated preoperative hemoglobin A1c levels are associated with an increased risk
      of readmission but not complications.

PMID- 24887925
TI  - Tumor thrombus in left atrium from pulmonary adenosquamous carcinoma.
AB  - We report a case of pulmonary adenosquamous carcinoma with a tumor thrombus in
      the left atrium. The left atrial tumor thrombus and lung cancer were removed via
      a right pneumonectomy and atriotomy under cardiopulmonary bypass. Simultaneous
      resection of a left atrial tumor thrombus and lung cancer can prevent systemic
      embolization, mitral obstruction, and sudden death, and improve the prognosis in
      selected patients. 

PMID- 24887926
TI  - Intrathoracic saline-filled prosthesis to treat postpneumonectomy syndrome.
AB  - Postpneumonectomy syndrome is a rare complication following pneumonectomy with
      its related change in mediastinal configuration. Symptoms range from airway
      obstruction to esophageal symptoms, leading at times to a persistent requirement
      for respiratory support. Surgery is often beneficial, which is in the form of
      placement of a prosthesis, with variable results. We report 2 cases of
      postpneumonectomy syndrome: one with successful relief, and the other in which
      the saline-filled prosthesis failed to achieve the desired result. 

PMID- 24887927
TI  - Survival and treatments in patients with incompletely resected thymoma.
AB  - OBJECTIVES: the objective of our study was to clarify survival and treatments in
      patients with incompletely resected thymoma. METHODS: between January 1991 and
      December 2012, 156 consecutive patients who underwent thymectomy with curative
      intent at Kyoto University Hospital, were evaluated retrospectively. Overall
      survival and progression-free survival were analyzed using the Kaplan-Meier
      method, comparing the complete resection group (n = 141) with the incomplete
      resection group (n = 15). Potentially relevant factors for overall survival and
      progression-free survival in patients with incompletely resected thymomas were
      analyzed using Cox proportional-hazard models. RESULTS: there was a significant
      difference in progression-free survival (p = 0.0012) but not in overall survival
      (p = 0.638) following thymectomy in the complete and incomplete resection groups.
      Adjuvant chemotherapy was performed in 6 (40%) patients and adjuvant radiotherapy
      in 6 (40%) in the incomplete resection group. In univariate analysis, younger age
      (p = 0.073) showed a tendency for better overall survival, and adjuvant
      chemotherapy (p = 0.071) showed a tendency for better progression-free survival.
      CONCLUSION: our results suggest that patients with incompletely resected thymomas
      can achieve comparable overall survival to those with completely resected
      thymomas. Adjuvant chemotherapy for incompletely resected thymomas tends to
      improve progression-free survival.

PMID- 24887928
TI  - Accidental pleural puncture by thoracic epidural catheterization.

PMID- 24887929
TI  - Transaxillary access to aortopulmonary window and paraaortic nodes.
AB  - A minimally invasive video-assisted thoracic surgery procedure to biopsy
      paraaortic and aortopulmonary window nodes is presented. In contrast to the
      standard 3-ports procedure, the transaxillary route we describe allows very good
      visualization of these anatomical zones. This procedure is safe and quick, and
      also cosmetic and painless. 

PMID- 24887930
TI  - Pneumopericardium due to Aspergillus empyema.

PMID- 24887931
TI  - Unstable angina due to protrusion of a left main trunk stent.

PMID- 24887932
TI  - An unusual air-fluid level in the thorax.

PMID- 24887933
TI  - Subclavian steal syndrome in a post-coronary artery bypass patient.

PMID- 24887934
TI  - Tumor with wires.

PMID- 24887935
TI  - Primary pericardial mesothelioma: a rare cause of constrictive pericarditis.

PMID- 24887936
TI  - Pneumopericardium and pneumomediastinum after esophageal bolus impaction.

PMID- 24887937
TI  - Apicoaortic conduit for severe hemolytic anemia after aortic valve replacement.
AB  - We describe the case of an 82-year-old woman who had undergone aortic mechanical
      valve replacement for aortic stenosis with a small annulus, and coronary artery
      bypass grafting. Four years after the operation, she began to experience
      hemolysis. Prosthetic valve obstruction was observed but there was no
      paravalvular leakage or aortic regurgitation through the mechanical valve. We
      elected to perform apicoaortic bypass in this patient with severe hemolytic
      anemia secondary to a mechanical valve malfunction. 

PMID- 24887938
TI  - Effect of packaging and season of milk production on selected quality
      characteristics of organic acid curd cheese during storage.
AB  - BACKGROUND: This study aimed to estimate the effect of the season of milk
      production and the packaging method on sensory characteristics and some
      physicochemical indices of fresh curd cheese stored in cooling conditions.
      MATERIAL AND METHODS: This study covered three seasons: autumn (October), winter
      (January) and spring (March/April). The experimental samples were vacuum packed
      in 50 or 100 MUm PE film, or in parchment paper and 50 or 100 MUm PE film. The
      evaluation was made on the day of production of the cheese and after 3, 7, 14 and
      21 days of cold storage. The tvarogs were subjected to the sensory evaluation,
      and also the investigation of moisture content, fat content, acidity, pH,
      hardness and the percentage of whey leakage was carried out. RESULT: It was found
      that among the sensory characteristics the deterioration in odour occurred fi rst
      in the course of storage, regardless of the packaging method applied. The method
      of packaging exerted no clear effect on moisture content, fat content and
      hardness of tvarogs. However, wrapping tvarogs additionally in parchment paper
      increased whey leakage, but also favourably affected cheese structure and
      consistency. CONCLUSIONS: Tvarog packed in parchment paper and 100 MUm PE film
      had the most desirable sensory characteristics in the course of storage. The
      shelf-life of the studied tvarog cheeses was as long as 7 days, regardless of the
      packaging method used and season of milk production.

PMID- 24887939
TI  - Effect of technological factors on water activity of extruded corn product with
      an addition of whey proteins.
AB  - BACKGROUND: The value of water activity in extruded products constitutes a
      significant indicator of their quality and stability. The state, in which water
      is found in extruded products, is an indicator of the conducted extrusion process
      and the used raw material. MATERIAL AND METHODS: The aim of the study was to
      assess water activity in extruded products made from a mixture of com grits with
      12.5 and 15.0% moisture contents and different level of addition of whey
      proteins. RESULTS AND DISCUSSION: It was shown that the degree of mixture
      moisture content did not have an effect on the value of aw in produced puffs. The
      greatest difference was recorded when introducing 3% proteins in comparison to aw
      of puffs produced solely from corn grits. Deltaaw = 0.023. The greater the
      content of whey proteins, the lower the aw value. A 3-month storage at a
      temperature of 18 +/-0.5 degrees C influenced aw of snacks produced from a
      mixture with a higher moisture content.

PMID- 24887940
TI  - Use of indigenous technology for the production of high quality cassava flour
      with similar food qualities as wheat flour.
AB  - BACKGROUND: The aim of the paper was to compare the food qualities of 2 varieties
      (SME 1 and 2) of high quality cassava flour (HQCF) produced from indigenous
      technology and that of some commercially sold wheat/HQCF samples. MATERIAL AND
      METHODS: The pH, proximate, phytochemical, antioxidant, functional properties and
      starch yield of the flours were carried out using standard techniques. RESULTS:
      The wheat flours had higher bulk densities and lipids than the HQCF samples while
      the oil absorption capacity of the HQCF (SME 2) was higher than other fl our
      samples investigated. The antioxidant assays of the flours showed that they
      contained considerable levels of antioxidants with the HQCF sample from DAT
      having higher antioxidants than other flour samples studied. The HQCF (SME 1) had
      significantly higher (P < 0.05) starch content among the flour samples. The
      bacteria counts of the HQCF samples ranged from 0 to 1.4 * 10(4) cfu/ml while the
      fungal count ranged from 0 to 2 * 10(-3) with the unbranded wheat fl our having
      the highest microbial load compared with other flour samples studied. CONCLUSION:
      The use of this indigenous technology produces HQCF with lower lipids, microbial
      contamination but higher flavour retaining ability, flavonoids and starch
      contents than wheat flour. The significant positive correlation (R2 = 0.872)
      between reducing power of the samples and their DPPH antioxidant activity
      indicate that either could be used to assay for the total antioxidant activity of
      cassava and wheat flour. The study underscores the need to buy flour from branded
      companies to reduce the risks of microbial contamination.

PMID- 24887941
TI  - Influence of extraction conditions on antioxidant properties of passion fruit
      (Passiflora edulis) peel.
AB  - BACKGROUND: As a by-product of tropical fruit juice industry, passion fruit peel
      is a valuable functional food. It is rich in antioxidants. To determine its
      potential antioxidant properties of passion fruit peel, this study aimed to
      evaluate the effect of extraction conditions on total phenolic content and
      antioxidant activity. METHODS: The extraction conditions were selected from
      different percentages of ethanol (0-100%, v/v), extraction times (60-300 min),
      and extraction temperatures (25-60 degrees C) that based on the optimal
      percentage of DPPH radical scavenging activity. The selected extraction condition
      was applied for further determination of total phenolic content (TPC) of the
      passion fruit peel extract using Folin-Ciocalteu reagent assay, while the
      antioxidant activities were evaluated using DPPH and ABTS radicals scavenging
      assays, ferric reducing antioxidant power (FRAP), and beta-carotene bleaching
      (BCB) assay. The best extraction conditions were 40% ethanol, 60 min extraction
      time, and extraction temperature of 30 degrees C. RESULTS: The chosen extraction
      conditions have contributed to the high TPC and antioxidant activity of passion
      fruit peel. The levels of antioxidant activity obtained from the passion fruit
      peel were also lower compared to BHA and alpha-tocopherol. Positive correlations
      were observed between TPC and antioxidant activities as assessed by DPPH, ABTS,
      FRAP, and BCB assays. CONCLUSION: As a waste of passion fruit consumption or by
      product of fruit juice industry, its peel could be considered as a potential
      source of natural antioxidant for possible functional food and industrial
      applications.

PMID- 24887942
TI  - Isolation, purification and characterisation of transglutaminase from rosemary
      (Rosmarinus officinalis L.) leaves.
AB  - BACKGROUND: Rosemary (Rosmarinus officinalis L.) is a spice and medicinal herb
      widely used around the world of the natural antioxidants, and it has been widely
      accepted as one of the spices with the highest antioxidant activity.
      Transglutaminase (EC 2.3.2.13: TGase) is an enzyme capable of catalysing acyl
      transfer reactions by introducing covalent cross-links between proteins, as well
      as peptides and various primary amines. TGase activity in plants was first
      observed in pea seedlings, and subsequently found in organs of both lower and
      higher plants. Recently. TGase has captured researchers' interest due to its
      attractive potential application in food industries. Therefore, the objectives of
      this study are isolation and purification of TGase from new plant source rosemary
      (Rosmarinus officinalis L.) leaves at the laboratory scale. Moreover,
      investigation of the biochemical properties of the purified TGase to provide a
      suitable TGase enzyme for food industry applications are in focus. MATERIAL AND
      METHODS: Rosemary (Rosmarinus officinalis L.) leaves was used as a new plant
      source to TGase. The biochemical characteristics of the crude and purified enzyme
      were determined. RESULTS: Rosemary (Rosmarinus officinalis L.) TGase was purified
      to homogeneity by successive three purification steps including ammonium sulfate
      precipitatation, ion exchange chromatography on DEAE-Sephadex A-50 column and
      Size exclusion column chromatography on Sephadex G-100 column. Under experimental
      conditions. 20-30% of ammonium sulfate saturation in the enzyme solution had a
      high yield of enzyme activity could be obtained. The purified enzyme from the
      Sephadex G-100 column had 21.35% yield with increased about 7.31 in purification
      fold. Rosemary TGase exhibited optimum activity at pH 7.0 and 55 degrees C for
      the catalytic reaction of hydroxylarnine and Z-Gln-Gly. The purified TGase almost
      maintained full activity after incubation for 15 ruin up to 60 degrees C and it
      was completely inactivated at 85 degrees C. The rosemary TGase was stimulated at
      2-6 rnM CaCl2 concentrations while it lost about 5-20% from its activity by
      increasing CaCl2 concentration. Sodium chloride (2-14%) shows no noticeable
      inhibition of the purified TGase activity. Mg+2, Ba+2 were acivited by the
      purified TGase while it was str ongly inhibited by Fe+2, moderately by Cir2 and
      Mn+2. CONCLUSION: This paper reports on the purification and characterisation of
      TGase from newly isolated plant, rosemary (Rosmarinus officinalis L.) leaves.
      Finding results of the TGase properties make this enzyme a good candidate for
      application in the food industry. However, additional work is required to
      increase activity yield during extraction and purification for commercial scale
      of TGase from this plant.

PMID- 24887943
TI  - Astaxanthin synthesis by Xanthophyllomyces dendrorhous DSM 5626 and its
      astaxanthin overproducing mutants on xylose media under different illumination.
AB  - BACKGROUND: Astaxanthin is the most important and expensive carotenoid pigment
      used in aquaculture. Its commercial attractiveness is also related with its
      antioxidant potential. Xanthophyllomyces dendrorhous yeast is considered to be
      promising for commercial production of astaxanthin. The aim of this study was to
      investigate the possibility of the growth and astaxanthin production by X.
      dendrorhous strains 011 media containing xylose under different illumination.
      MATERIAL AND METHODS: A', dendrorhous DSM 5626 and its mutants: 10BE and 26UV
      were used in this study. The cultures were carried out 011 hydrolysed rye
      stillage (HS) and YM medium with xylose (YM-K). Cell concentration, total
      carotenoid and astaxanthin yields were assessed in 5-day cultures. The effect of
      illumination in the range of 0-5.000 lx 011 growth and on astaxanthin production
      of yeasts in cultures run 011 YM-K medium was also examined. RESULTS: For the
      tested yeast strains better growth parameters and astaxanthin yields were
      obtained on the YM-K medium. 011 which for all strains the highest pigment yields
      were recorded at 600-1.000 lx. The highest concentration of astaxanthin in cells
      was recorded for 26UV in a culture at 1.000 lx (0.51 g?kg-1 DCW). The volume
      yield of the pigment regardless of strain was highest in cultures at 600 lx. In
      this case 10BE was found to be the best astaxanthin producer with a yield of 2.15
      mg dm-3. CONCLUSIONS: Astaxanthin synthesis in X. dendrorhous DSM 5626 and its
      mutants was better 011 YM-K medium comparing to hydrolysed rye stillage.
      Moreover, carotenogenesis in the studied yeast strains was subjected to marked
      photoregulation. Illumination within the range of 600-1.000 lx promotes
      carotenogenesis and astaxanthin production, while exceeding a certain light
      capacity results in microbial cell death.

PMID- 24887945
TI  - Share of dietary supplements in nutrition of coeliac disease patients.
AB  - INTRODUCTION: The aim of the study was to assess the intake of vitamins and
      minerals from the food ration and levels recorded after synthetic supplementation
      in patients following a gluten-free diet. MATERIAL AND METHODS: The study
      included a cohort of 25 individuals aged 20-54. Nutrient intakes were assessed
      based on a 24-hour diet recall interview and an original questionnaire prepared
      by the authors specifically for this study. Anthropometric measurements were
      recorded in order to assess the nutritional status of the patients. RESULTS AND
      DISCUSSION: A low energy intake and an excessive share of fat were observed in
      daily food rations of coeliac disease patients. Uptake of most minerals with the
      diet was too low, while that of vitamins too high. Most participants declared the
      administration of supplements, which greatly contributed to the coverage of
      requirements for these nutrients. CONCLUSIONS: It was observed that the
      administered supplementation was frequently unjustified, which led to the
      allowances being considerably exceeded for many vitamins and minerals.

PMID- 24887944
TI  - The structure, occurrence and biological activity of ellagitannins: a general
      review.
AB  - The present paper deals with the structure, occurrence and biological activity of
      ellagitannins. Ellagitannins belong to the class of hydrolysable tannins, they
      are esters of hexahydroxydiphenoic acid and monosaccharide (most commonly
      glucose). Ellagitannins are slowly hydrolysed in the digestive tract, releasing
      the ellagic acid molecule. Their chemical structure determines physical and
      chemical properties and biological activity. Ellagitannins occur naturally in
      some fruits (pomegranate, strawberry, blackberry, raspberry), nuts (walnuts,
      almonds), and seeds. They form a diverse group of bioactive polyphenols with anti
      inflammatory, anticancer, antioxidant and antimicrobial (antibacterial,
      antifungal and antiviral) activity. Furthermore, they improve the health of blood
      vessels. The paper discusses the metabolism and bioavailability of ellagitannins
      and ellagic acid. Ellagitannins are metabolized in the gastrointestinal tract by
      intestinal microbiota. They are stable in the stomach and undergo neither
      hydrolysis to free ellagic acid nor degradation. In turn, ellagic acid can be
      absorbed in the stomach. This paper shows the role of cancer cell lines in the
      studies of ellagitannins and ellagic acid metabolism. The biological activity of
      these compounds is broad and thus the focus is on their antimicrobial, anti
      inflammatory and antitumor properties. Ellagitannins exhibit antimicrobial
      activity against fungi, viruses, and importantly, bacteria, including antibiotic
      resistant strains such as methicillin-resistant Staphylococcus aureus.

PMID- 24887946
TI  - Comparison between the nutritional quality of flour obtained from raw, roasted
      and fermented sesame (Sesamum indicum L.) seed grown in Nigeria.
AB  - BACKGROUND: The most common form of utilization of sesame seed is its roasting,
      which supplies nutrients to the diet. Therefore, in view of the nutritional
      values of sesame seeds, the present study aimed at investigating the effect of
      roasting and fermentation 011 the nutritional quality of sesame flour. MATERIAL
      AND METHODS: Nigeria grown white sesame seeds (NC'RI-98-60) were collected from
      National Cereal Research Institute (NCRI). Badegi. Nigeria. The seeds were
      divided into three portions, and treated as raw. roasted and fermented sesame
      seeds respectively. Each of the samples was milled, sieved and analysed for
      chemical composition using standard methods. Animal studies were used to evaluate
      the raw and processed sesame in terms of nutritional and histopathological
      qualities. RESULTS: The ranges of proximate contents from sesame were: protein
      15.4-26.5 g/100 g. fat 52.4-62.8 g/100 g, crude fibre 3.34-3.89 g/100 g. ash 3.93
      6.78 g/100 g. carbohydrate 11.7-13.4 g/100 g and energy value 550.7-593.7 kcal/g.
      Among the minerals, calcium was highest (464-567 mg/100 g) followed by phosphorus
      (442-508 mg/100 g). magnesium (399-455 mg/100 g) and potassium (336-489 mg/100
      g). Total essential amino acid was within the range of 26.66-32.73 mg/100 g and
      these values were higher than FAO/WHO dietary requirement for infant and adult.
      Fatty acid profiles of raw. roasted and fermented sesame showed a predominance of
      oleic acid (46.43%, 44.20%, and 43.16%, respectively) followed by linoleic acid
      (36.76%. 39.02%, and 39.67%); while the least was behenic acid. The
      unsaturated/saturated fatty acid ratio ranges between 5.01-5.13. Phytate and
      oxalate concentrations of fermented sesame were significantly reduced than other
      food samples. In general, fermented sesame was found to have to have better
      nutritional quality as indicated by rat growth response. Correspondingly, the
      Food Efficiency Ratio (FER) value of 0.16 was higher than raw and roasted sesame
      respectively. Significantly higher Protein Efficiency Ratio (PER) value was also
      obtained for fermented sesame. The organ to body ratios of the test animals were
      influenced by treatments as recorded on heart, kidney, spleen, liver and
      pancreas. CONCLUSION: The present study investigated the effect of roasting and
      fermentation 011 the nutritional quality of sesame flour. The findings showed
      that roasting and fermentation could enhance the nutritional quality of sesame
      seeds without detrimental effect 011 human.

PMID- 24887948
TI  - Peripartum cardiomyopathy - risk factors, characteristics and long-term follow
      up.
AB  - AIMS: Peripartum cardiomyopathy (PPCM) is an infrequent form of cardiomyopathy
      causing significant maternal morbidity and mortality. We aimed to evaluate the
      risk factors, characteristics and prognosis of PPCM during the index and
      subsequent pregnancies. METHODS: A retrospective cohort of 36 women with PPCM in
      a tertiary medical center was analyzed and compared with 10,370 women who gave
      birth during a single calendar year at the same institution. RESULTS: Women
      diagnosed with PPCM were older (mean 33.5 years) than controls. A significantly
      higher proportion were primiparous (63.9%), carried multifetal pregnancies
      (33.3%) and had hypertensive pregnancy complications (38.9%). Thirty-six percent
      of PPCM patients conceived with in vitro fertilization, and six of them received
      ovum donation. Twenty-two women had severe left ventricular dysfunction at
      diagnosis, and these women tended to remain with residual disease, compared with
      women with milder ventricular dysfunction at diagnosis. Eight patients recovered
      completely within 2 weeks of diagnosis. Women who recovered early (n=8) had
      significantly higher ejection fractions on last follow-up compared with women
      (n=28) who had late or partial recovery. Nine women had 14 additional
      pregnancies; of them eight women had normal cardiac functions on subsequent
      pregnancy. CONCLUSIONS: Risk factors for peripartum cardiomyopathy include
      primiparity, hypertension and multifetal pregnancies. Assisted reproduction
      techniques are not independently associated with PPCM but rather through other
      risk factors for PPCM. The degree of cardiac dysfunction at diagnosis and time to
      recovery are important prognostic factors.

PMID- 24887947
TI  - Characteristics of the peanut chain in Europe - implications for peanut allergy.
AB  - BACKGROUND: Peanuts are one of the main food allergens, occasionally responsible
      for life-threatening reactions. Thus, many studies have tried to fi nd a
      connection between peanut allergy prevalence and processes in the peanut chain
      that may contribute to the peanut allergenicity. To inform this discussion, this
      paper outlines experiences in peanut cultivation, trade and processing in Europe,
      focusing on four European countries with different peanut experiences (Poland,
      Bulgaria, Spain and the UK). MATERIAL AND METHOD: Results here are based on
      documentary analysis and semi-structured, face-to-face interviews with 32 experts
      involved in various stages of the peanut chain, including peanut farmers,
      processors, traders, food technologists and manufacturers. RESULTS: A common
      peanut chain diagram has been drawn considering shelled and in-shell peanuts. The
      analysis of each stage of peanut processing has been made in accordance with this
      peanut chain schema. Thermal and mechanical processes are discussed alongside the
      resultant end peanut products available for European consumers. The paper also
      analyses the main trends of peanut trade in Europe. The results suggest that the
      majority of peanut products in Europe are roasted, implying enhanced exposure of
      the population to more allergenic peanuts. CONCLUSION: The presented schema and
      related discussion bring together diverse aspects of peanut production, trade and
      processing. The main factor associated with the increased allergenicity of
      peanuts appears to be high temperature roasting. Frying and boiling are also
      thermal processes, but fried and boiled peanuts have been associated with reduce
      peanut allergenicity. Neither country of origin nor cultivar type appear to be
      related to differential peanut allergenicity. More research is needed as regards
      the impact of various additives, such as chocolate (which is also considered an
      allergen) on the allergenicity of peanut products. The use of peanuts in non-food
      products also needs more investigation.

PMID- 24887949
TI  - Aortic dilatation and dissection in Turner syndrome: what we know, what we are
      unclear about and what we should do in clinical practice?
AB  - Aortic dilatation and aortic dissection are increasingly recognised in patients
      with Turner syndrome (TS). Risk factors for aortic dissection include aortic
      dilatation, bicuspid aortic valves, coarctation of aorta and pregnancy. The risk
      of death due to aortic dissection in pregnancy in TS is 2%, which is
      approximately 100 times higher than the general population, as maternal mortality
      is extremely low. Ongoing cardiovascular monitoring is recommended, although
      there remain several unanswered questions in relation to cardiovascular imaging
      especially the choice of modality for detection of vascular, valvular
      abnormalities and measurements of aortic dimensions. Due to the relative short
      stature of patients with TS, aortic dimensions need to be defined by aortic
      measurements adjusted for body surface area, known as aortic sized index (ASI).
      The relationship of ASI and other risk factors with aortic dissection is only
      beginning to be clarified. Clinical management and monitoring of such patients
      should be delivered by a group of clinicians familiar with the issues unique to
      TS patients in a multidisciplinary fashion. All clinicians including the non
      specialists need to have a low threshold of suspecting aortic dissection in these
      adolescents and young adults. This up to date review, including a summary of all
      122 published cases of TS patients with aortic dissection, aims to provide a
      summary of recent publications on characteristics of aortic dissection and aortic
      dilatation in TS to highlight gaps in knowledge and propose possible clinical
      monitoring pathway of cardiovascular health in children and adults with TS.
      Cardiovascular assessment and risk counselling is especially crucial during the
      period of transition of adolescents with TS, although life long monitoring by
      expert cognizant to the issues specific in TS is essential.

PMID- 24887950
TI  - Outcome of adolescents with eating disorders from an adolescent medicine service
      at a large children's hospital.
AB  - OBJECTIVE: To describe outcomes of adolescents with eating disorders treated by
      an interdisciplinary adolescent medicine service at a large children's hospital
      and to identify factors, including hospitalization, associated with outcome.
      DESIGN: The study design was a retrospective chart review of patients. SETTING:
      The setting was an inpatient and outpatient adolescent service in a large urban
      children's hospital. PARTICIPANTS: A total of 218 adolescents diagnosed with
      anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified
      participated in the study. INTERVENTION: Interdisciplinary inpatient and
      outpatient treatment for eating disorders was adopted for intervention. OUTCOME
      MEASURES: Patient outcomes were categorized as fully recovered, partially
      recovered/improved, or poorly recovered/exhibiting chronicity. RESULTS: Being
      admitted to the study hospital once and longer duration of follow-up were
      associated with full or partial recovery. In contrast, being readmitted to the
      study hospital and longer duration of illness prior to the initial contact with
      this service were associated with poor recovery. Premorbid obesity was unrelated
      to outcome. CONCLUSIONS: Earlier detection and referral of adolescents with
      eating disorders are needed because a high percentage of patients, especially
      those with anorexia nervosa, required hospitalization at initial contact. The
      benefits of inpatient admission may extend beyond medical stabilization of the
      most medically compromised patients to include improved therapeutic relationship
      with the treatment team and improved follow-up. Many patients prematurely
      terminate treatment; factors contributing to premature termination of therapy
      need further exploration.

PMID- 24887951
TI  - Health care providers and adolescents' perspectives towards adolescents' health
      education needs: a need assessment based on comparative approach.
AB  - AIM: Health care providers have considerable influence on adolescents' health
      promotion. Thus, it is important to focus on the views of this group as one of
      the most reliable sources in the evaluation of teenagers' health needs. The aim
      of this study was to compare the attitudes of Iranian health care providers and
      adolescents towards the latter's health education needs. MATERIALS AND METHODS: A
      quantitative cross-sectional survey, including 72 health care providers and 402
      female students from 14 high schools in northern Iran, was carried out in 2011.
      Topics in a self-administrated questionnaire covered the participants'
      perspectives towards the educational health needs of adolescents in a five-point
      Likert scale. RESULTS: Findings revealed from health care providers' views
      indicate that the highest mean score was assigned to "Education about prevention
      of sexual high risk behavior", which was significantly different from
      adolescents' perspective (t=8.42, p<0.05). RESULTS showed that health care
      providers and adolescents both emphasized on the mothers' role as the most
      reliable source of adolescents' education (t=1.85, p>0.05). CONCLUSION: Provision
      of health education programs for adolescents, which are based on integration of
      health care providers' perspectives and the adolescents' views, are essential in
      meeting adolescents' educational health needs.

PMID- 24887952
TI  - Characteristics of hand sanitizer ingestions by adolescents reported to poison
      centers.
AB  - BACKGROUND: There had been reports of adolescents using hand sanitizers to obtain
      alcohol and ending up in emergency departments with alcohol poisoning. OBJECTIVE:
      This study aimed to describe the pattern of adolescent ingestions of hand
      sanitizers reported to a statewide poison center system. SUBJECTS: Our study
      subjects included patients aged 13-19 years who reported hand sanitizer
      ingestions as reported to Texas poison centers during 2000-2013. MATERIALS AND
      METHODS: The distribution of the ingestions was determined for various
      demographic and clinical factors. RESULTS: Of 385 total cases, 61% of the
      patients were male, and the mean age was 15.3 years. The ingestion reason was
      unintentional (61%), intentional abuse/misuse (18%), and malicious (10%).
      Ingestion site was most frequently reported to be the patient's own residence
      (53%), followed by school (35%). About 77% of the patients were managed on site.
      The medical outcome was serious (moderate effect or unable to follow-potentially
      toxic) in 5% of the cases. The most frequently reported adverse clinical effects
      were vomiting (5%), abdominal pain (4%), nausea (4%), throat irritation (4%), and
      drowsiness (2%). CONCLUSION: Adolescents who ingested hand sanitizers were more
      likely to be male and younger. One-third of the ingestions occurred at school,
      suggesting that school personnel might be made aware of the potential problem of
      hand sanitizer ingestions by adolescents. Nevertheless, despite the potential for
      serious outcomes from adolescent hand sanitizer ingestion, most of the ingestions
      reported to poison centers are not likely to be serious and can be successfully
      managed outside of a healthcare facility.

PMID- 24887953
TI  - Study of menstrual patterns in adolescent girls with disabilities in a
      residential institution.
AB  - BACKGROUND: The gynecological health needs of girls with disabilities is an issue
      related to their rights as individuals. OBJECTIVE: The objective of this study is
      to describe the menstrual pattern of girls with disabilities. MATERIALS AND
      METHODS: A descriptive study was undertaken on thirty girls with different types
      of disabilities in a residential institution. The diagnosis, type of disability,
      secondary sexual characters, age at menarche, menstrual pattern and practice of
      menstrual hygiene was noted. RESULTS: The girls with intellectual disabilities
      had later age of menarche, irregular cycles and more behaviour problems. The
      girls with hearing impairment and locomotor disabilities had normal menstrual
      pattern. The girl with low vision had earlier menarche and regularized cycles.
      Girls with normal intelligence and mild intellectual disabilities were
      independent in maintaining menstrual hygiene. The menstrual disorders are managed
      conservatively in accordance with latest guidelines. CONCLUSION: Onset of
      menarche is towards the extremes of normal age range in girls with intellectual
      disabilities or visual impairment but not in girls with hearing impairments or
      locomotor disabilities. Girls with disabilities have potential for independent
      menstrual care. Menstrual disorders were managed conservatively.

PMID- 24887955
TI  - Pubertal development profile in patients with Turner syndrome.
AB  - INTRODUCTION: Puberty can be divided into two independent events: adrenarche and
      gonadarche. In healthy children, adrenarche is followed by gonadarche, but in
      patients with gonadal dysgenesis there is partial or complete dissociation
      between these two events. OBJECTIVE: To evaluate the age and chronology of the
      development of secondary sexual characteristics and occurrence of these events
      and their relationship to the induction of puberty in patients with Turner
      syndrome (TS). MATERIALS AND METHODS: A descriptive analysis with historical
      records of the patients with clinical and cytogenetic TS was conducted. The
      following variables were recorded: karyotype; age of thelarche, pubarche, and
      menarche; occurrence of spontaneous puberty; maintenance of puberty or secondary
      failure; and the onset of hormone replacement therapy (HRT) with estrogen.
      RESULTS: We evaluated 123 medical charts. Seven (5.7%) patients were prepubertal,
      10 (8.1%) had only pubarche, and 5 (4%) had only thelarche. Forty-seven (38.2%)
      patients entered puberty spontaneously. Among these, 35 (28.5%) remained in
      puberty, and 12 (9.8%) required subsequent HRT; 54 (44%) had puberty induced.
      Sixty-six (56.9%) patients had pubarche started before thelarche. Menarche
      occurred in 67 patients, spontaneously in 19. Pubarche spontaneously presented in
      91 (78.4%) patients, and in 25 (21.5%) after HRT introduction. CONCLUSIONS:
      Spontaneous puberty occurred in approximately one-third of the patients. Pubarche
      was the first feature in most patients and about 20% showed pubarche only after
      estrogen therapy.

PMID- 24887956
TI  - Dopamine and reward seeking: the role of ventral tegmental area.
AB  - Reward seeking is controlled by conditioned stimuli (CSs). There is a positive
      relation between mesocorticolimbic dopamine (DA) and the performance of learned
      reward-directed behavior. The mechanisms by which reward-, including drug-,
      associated stimuli come to acquire the capacity to activate the DA systems are
      not fully understood. In this review, we discuss the possible neurochemical
      mechanisms within the ventral tegmental area that may be involved in how CSs
      acquire the capacity to activate ventral tegmental area (VTA) DA neurons based on
      principles of long-term potentiation in the VTA and the role of mesocorticolimbic
      DA in reward-related learning. We propose that CSs function as such because they
      acquire the capacity to activate VTA DA neurons. Furthermore, CSs come to acquire
      this control of VTA DA cells when there is coincident N-methyl-d-aspartate
      receptor stimulation on VTA DA cells and strong depolarization of VTA DA cells,
      possibly by muscarinic acetylcholine receptor stimulation on these cells. This
      coincident activity leads to the strengthening of CS-associated glutamatergic
      synapses and the control by CSs of mesocorticolimbic DA systems and reward
      directed behavior.

PMID- 24887957
TI  - Modulatory effects of cod liver oil on the antioxidant status and oxidative
      stress induced by acute exposure to carbon tetrachloride (CCL4) in experimental
      animal models.
AB  - BACKGROUND: This work was designed to investigate the modulatory effects of cod
      liver oil on the acute exposure to carbon tetrachloride (CCL4) in experimental
      animal models. METHODS: Markers of oxidative stress, enzymic and non-enzymic
      antioxidants were assessed in the liver and kidney. RESULTS: The results showed
      significant (p<0.05) increase in the total protein of the kidney of rats
      pretreated with cod liver oil compared to the control and CCL4-treated groups.
      Acute exposure to CCL4 also significantly (p<0.05) increased thiobarbituric acid
      reactive substances in the liver of rats treated with cod liver oil compared to
      the CCL4-treated rats. The reduced glutathione (GSH) content in the liver of the
      rats administered with CCL4 decreased significantly compared to that in all other
      treatment groups, whereas rats pretreated and co-administered with cod liver oil
      and CCl4 showed significant (p<0.05) improvement in the liver GSH content. The
      catalase (CAT) activity in the liver of rats exposed to CCL4 decreased (p<0.05)
      significantly, whereas the activity increased (p<0.05) significantly in the rats
      that were treated with cod liver oil compared to the CCl4 only-treated group. The
      percentage inhibition of superoxide dismutase (SOD) increased (p<0.05)
      significantly in the liver of rats administered cod liver oil compared to the
      CCL4-treated rats and the control. CONCLUSIONS: Taken together, cod liver oil
      attenuates CCL4-induced toxicity and oxidative stress in the liver but not in the
      kidney of rats acutely exposed to CCL4.

PMID- 24887958
TI  - Impact of assay design on test performance: lessons learned from 25
      hydroxyvitamin D.
AB  - BACKGROUND: Current automated immunoassays vary significantly in many aspects of
      their design. This study sought to establish if the theoretical advantages and
      disadvantages associated with different design formats of automated 25
      hydroxyvitamin D (25-OHD) assays are translated into variations in assay
      performance in practice. METHODS: 25-OHD was measured in 1236 samples using
      automated assays from Abbott, DiaSorin, Roche and Siemens. A subset of 362
      samples had up to three liquid chromatography-tandem mass spectrometry 25-OHD
      analyses performed. 25-OHD2 recovery, dilution recovery, human anti-animal
      antibody (HAAA) interference, 3-epi-25-OHD3 cross-reactivity and precision of the
      automated assays were evaluated. RESULTS: The assay that combined release of 25
      OHD with analyte capture in a single step showed the most accurate 25-OHD2
      recovery and the best dilution recovery. The use of vitamin D binding protein
      (DBP) as the capture moiety was associated with 25-OHD2 under-recovery, a trend
      consistent with 3-epi-25-OHD3 cross-reactivity and immunity to HAAA interference.
      Assays using animal-derived antibodies did not show 3-epi-25-OHD3 cross
      reactivity but were variably susceptible to HAAA interference. Not combining 25
      OHD release and capture in one step and use of biotin-streptavidin interaction
      for solid phase separation were features of the assays with inferior accuracy for
      diluted samples. The assays that used a backfill assay format showed the best
      precision at high concentrations but this design did not guarantee precision at
      low 25-OHD concentrations. CONCLUSIONS: Variations in design among automated 25
      OHD assays influence their performance characteristics. Consideration of the
      details of assay design is therefore important when selecting and validating new
      assays.

PMID- 24887959
TI  - Procalcitonin in early rule-in/rule-out of sepsis in SIRS patients admitted to a
      medical ward.
AB  - BACKGROUND: A relevant amount of patients with clinical suspect of sepsis is
      admitted and treated in medical wards (MW). These patients have a better
      prognosis but are older and with more comorbidities compared to those admitted to
      intensive care units (ICU). Procalcitonin (PCT) is extensively used in emergency
      departments for the diagnosis of sepsis, but its accuracy in the setting of a MW
      has not been thoroughly investigated. Predicted low PCT levels also call for the
      comparison of immunomagnetic-chemiluminescent (L-PCT) and time-resolved amplified
      cryptate emission (TRACE, K-PCT) technologies, in PCT determination. METHODS: In
      80 patients with systemic inflammatory response syndrome (SIRS) diagnostic
      criteria and suspect of sepsis newly admitted to a MW, PCT was determined with L-
      and K-PCT method. RESULTS: Sixty patients were diagnosed as sepsis (20
      microbiologically and 40 clinically proven) and 20 with non-infective SIRS. The
      sepsis group had significantly higher levels of both PCTs, with no differences
      between the clinically and microbiologically proven subgroups. The areas under
      ROC curves for L- and K-PCT were 0.72 and 0.78 (p<0.001 for each), respectively.
      Based on MW customized cut-off values of 0.150 (L-PCT) and 0.143 ng/mL (K-PCT),
      overall accuracies were 66.8 (95% CI 58.7-78.9) and 78.2% (69.8-87.2),
      respectively, compared to the 55% (44.2-66) of 0.5 ng/mL canonical cut-off.
      Neither PCT-L nor -K held prognostic value on survival. CONCLUSIONS: In MW
      patients, customized PCT cut-off levels provide better accuracy than customary
      levels adopted from ICU, and TRACE technology seems to offer a wider analysis
      range.

PMID- 24887960
TI  - May thrombopoietin be a useful marker of sepsis severity assessment in patients
      with SIRS entering the emergency department?
AB  - BACKGROUND: Thrombopoietin (TPO), a growth factor primarily involved in
      regulating thrombopoiesis, has been recently implicated in the pathogenesis of
      sepsis. TPO levels are, indeed, greatly increased in patients with sepsis
      compared to control subjects, and correlate with sepsis severity. The aim of this
      study was to evaluate TPO as predictive biomarker of sepsis and of sepsis
      severity in patients entering the emergency department (ED) with systemic
      inflammatory response syndrome (SIRS). METHODS: This was a prospective
      observational study. Ours is a sub-study of the 'Need-speed trial', a multi
      center observational study involving six Italian centers affiliated to the GREAT
      Italian Network. TPO was measured by ELISA. RESULTS: We enrolled 13 patients with
      SIRS (6 with acute pancreatitis, 3 with acute heart failure, 1 with pulmonary
      embolism, and 3 with allergic reactions), and 40 patients with sepsis, eight of
      whom had severe sepsis and three septic shock. TPO was significantly higher in
      patients with sepsis than with SIRS. In addition, TPO was higher in patients with
      severe sepsis than with sepsis, and in patients with septic shock than with
      severe sepsis, although these differences did not reach the statistical
      significance. CONCLUSIONS: Our preliminary results suggest that TPO may have the
      potential to be considered a promising early biomarker for both the diagnosis of
      sepsis and the assessment of sepsis severity in patients with SIRS entering the
      ED.

PMID- 24887961
TI  - Structural myocardial alterations in diabetes and hypertension: the role of
      galectin-3.
AB  - BACKGROUND: Galectin-3 is a protein widely distributed in the heart, brain and
      blood vessels, and has a regulatory role in inflammation, immunology and cancer.
      Many studies demonstrated that the increased level of galectin-3 is associated
      with progressive fibrosis and stiffening of the myocardium. The aim of this study
      was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D)
      and/or arterial hypertension (HT). METHODS: Study population included 189
      patients, with no coronary artery disease, divided into three groups: group 1
      (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine
      laboratory tests, as well as specific biomarkers assessment [galectin-3,
      glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide
      (NT-proBNP)]. Cardiological evaluation included physical examination,
      transthoracic tissue Doppler echocardiography and stress echocardiography.
      RESULTS: The results of this study demonstrated significantly increased levels of
      galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left
      ventricular (LV) diameters and IVS thickness were increased in this group of
      patients. Furthermore, in the same cohort a positive correlation between galectin
      3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a
      negative correlation between galectin-3 and LV end-diastolic diameter was
      revealed. CONCLUSIONS: This study revealed that levels of galectin-3 were higher
      in patients with both T2D and HT, and correlated with LV mass, indicating the
      potential role of this biomarker for early detection of myocardial structural and
      functional alterations.

PMID- 24887962
TI  - Harmonisation of seven common enzyme results through EQA.
AB  - BACKGROUND: Equivalent results between different laboratories enable optimal
      patient care and can be achieved with harmonisation. We report on EQA-initiated
      national harmonisation of seven enzymes using commutable samples. METHODS: EQA
      samples were prepared from human serum spiked with human recombinant enzymes.
      Target values were assigned with the IFCC Reference Measurement Procedures. The
      same samples were included at four occasions in the EQA programmes of 2012 and
      2013. Laboratories were encouraged to report IFCC traceable results. A parallel
      study was done to confirm commutability of the samples. RESULTS: Of the 223
      participating laboratories, 95% reported IFCC traceable results, ranging from 98%
      (ASAT) to 87% (amylase). Users of Roche and Siemens (97%) more frequently
      reported in IFCC traceable results than users of Abbott (91%), Beckman (90%), and
      Olympus (87%). The success of harmonisation, expressed as the recovery of
      assigned values and the inter-laboratory CV was: ALAT (recovery 100%; inter-lab
      CV 4%), ASAT (102%; 4%), LD (98%; 3%), CK (101%; 5%), GGT (98%; 4%), AP (96%;
      6%), amylase (99%; 4%). There were no significant differences between the
      manufacturers. Commutability was demonstrated in the parallel study. Equal
      results in the same sample in the 2012 and 2013 EQA programmes demonstrated
      stability of the samples. CONCLUSIONS: The EQA-initiated national harmonisation
      of seven enzymes, using stable, commutable human serum samples, spiked with human
      recombinant enzymes, and targeted with the IFCC Reference Measurement Procedures,
      was successful in terms of implementation of IFCC traceable results (95%),
      recovery of the target (99%), and inter-laboratory CV (4%).

PMID- 24887963
TI  - Empowerment and mentoring in nursing academia.
AB  - In 2011, there was an expected shortage of 200 full-time faculty. While there are
      an estimated 322 graduate students in Nurse Practitioner and Masters/PhD programs
      in Canada today, the supply of potential new faculty falls short of the
      anticipated demand in the years ahead (Canadian Association of Schools of
      Nursing). This mixed method study explored how organizational culture and the
      perceived level of psychological and structural empowerment are associated with
      one's work environment among Canadian nursing faculty and to explore the state of
      mentorship in schools of nursing.

PMID- 24887965
TI  - Squamomelanocytic tumor: a case report and further insights into its possible
      histogenesis.
AB  - We report a case of combined squamomelanocytic tumor of the skin. Clinically, the
      lesion was felt to be a squamous cell carcinoma. Histologically, it was
      characterized by large epithelioid cells admixed with basaloid cells with central
      squamous differentiation. Immunohistochemical staining showed both cell
      populations to be reactive with Melan A, BEREP4, and Pan Keratins.
      Ultrastructural studies revealed simultaneous features of squamous
      differentiation (dense cytoplasmic tonofilaments with well-developed desmosomes)
      and melanocytic differentiation (mature/pigmented melanosomes) in the same cell
      population. This is the second reported case in the English literature with
      documented biphenotypic or divergent differentiation at the ultrastructural
      level. The behavior of squamomelanocytic tumor is uncertain given the rarity of
      reported cases.

PMID- 24887966
TI  - Viral-associated trichodysplasia secondary to antineoplastic treatment in a
      patient with lymphoblastic leukemia.
AB  - Viral-associated trichodysplasia spinulosa is an unusual condition with
      distinctive clinical and histopathological features. Initially described in
      patients immunosupressed as a result of solid organ transplantation, it has also
      been reported in patients treated with immunosuppressive drugs other than
      cyclosporine or being treated for hematological malignancies. Patients presented
      with disseminated follicular, hyperkeratotic papules, and variable degrees of
      alopecia. Histopathological examination revealed shaftless bulbous and dilated
      hair follicles with keratotic plugging of the infundibulum. The authors reported
      a case of viral-associated trichodysplasia in a 5-year-old boy treated for a
      lymphoblastic leukemia. Eruption persisted, although treated with emollients and
      keratolytics, but resolved spontaneously after completing the antineoplastic
      medication.

PMID- 24887967
TI  - Disability predictors in chronic low back pain after aquatic exercise.
AB  - The physical and psychological factors associated with reduction of disability
      after aquatic exercise are not well understood. Sixty participants (30 men and 30
      women; age, 50.60 [9.69] yrs; body mass index, 27.21 [5.20] kg/m2) with chronic
      low back pain were prospectively recruited. The 8-wk aquatic therapy program was
      carried out in an indoor pool sized 25 * 6 m, with 140-cm water depth and 30
      degrees C (1 degrees C) of water temperature, where patients exercised for 2-5
      days a week. Each aquatic exercise session lasted 55-60 mins (10 mins of warm-up,
      20-25 mins of aerobic exercise, 15-20 mins of resistance exercise, and 10 mins of
      cooldown). Demographic information, disability (Oswestry Disability Index), back
      pain (visual analog scale), quality-of-life (Short Form 36), abdominal muscular
      endurance (curl-up), handgrip strength, trunk flexion and hamstring length (sit
      and reach), resting heart rate, and body mass index were outcomes variables.
      Significant correlations between change in disability and visual analog scale (at
      rest, flexion, and extension), curl-up and handgrip (r ranged between -0.353 and
      0.582, all Ps < 0.01) were found. Changes in pain and abdominal muscular
      endurance were significant predictors of change in disability after therapy.

PMID- 24887969
TI  - Serotonin, morphine, and neuropathic pain: not a simple story.

PMID- 24887968
TI  - Peripheral nerve injury reduces analgesic effects of systemic morphine via spinal
      5-hydroxytryptamine 3 receptors.
AB  - BACKGROUND: Morphine produces powerful analgesic effects against acute pain, but
      it is not effective against neuropathic pain, and the mechanisms underlying this
      reduced efficacy remain unclear. Here, the authors compared the efficacy of
      systemic morphine between normal rats and rats with peripheral nerve injury, with
      a specific focus on descending serotonergic mechanisms. METHODS: After L5 spinal
      nerve ligation injury, male Sprague-Dawley rats were subjected to behavioral
      testing, in vivo microdialysis of the spinal dorsal horn to determine serotonin
      (5-hydroxytryptamine [5-HT]) and noradrenaline release, and immunohistochemistry
      (n = 6 in each group). RESULTS: Intraperitoneal administration of morphine (1, 3,
      or 10 mg/kg) produced analgesic effects in normal and spinal nerve ligation rats,
      but the effects were greater in normal rats (P < 0.001). Morphine increased 5-HT
      release (450 to 500% of the baseline), but not noradrenaline release, in the
      spinal dorsal horn via activation of serotonergic neurons in the rostral
      ventromedial medulla. Intrathecal pretreatment with ondansetron (3 MUg), a 5-HT3
      receptor antagonist, or 5,7-dihydroxytryptamine creatinine sulfate (100 MUg), a
      selective neurotoxin for serotonergic terminals, attenuated the analgesic effect
      of morphine (10 mg/kg) in normal rats but increased the analgesic effect of
      morphine in spinal nerve ligation rats (both P < 0.05). CONCLUSIONS: Systemic
      administration of morphine increases 5-HT levels in the spinal cord, and the
      increase in 5-HT contributes to morphine-induced analgesia in the normal state
      but attenuates that in neuropathic pain through spinal 5-HT3 receptors. The
      plasticity of the descending serotonergic system may contribute to the reduced
      efficacy of systemic morphine in neuropathic pain.

PMID- 24887970
TI  - Video-based peer feedback through social networking for robotic surgery
      simulation: a multicenter randomized controlled trial.
AB  - OBJECTIVE: To examine the feasibility and outcomes of video-based peer feedback
      through social networking to facilitate robotic surgical skill acquisition.
      BACKGROUND: The acquisition of surgical skills may be challenging for novel
      techniques and/or those with prolonged learning curves. METHODS: Randomized
      controlled trial involving 41 resident physicians performing the Tubes (Da Vinci
      Intuitive Surgical, Sunnyvale, CA) simulator exercise with versus without peer
      feedback of video-recorded performance through a social networking Web page. Data
      collected included simulator exercise score, time to completion, and comfort and
      satisfaction with robotic surgery simulation. RESULTS: There were no baseline
      differences between the intervention group (n = 20) and controls (n = 21). The
      intervention group showed improvement in mean scores from session 1 to sessions 2
      and 3 (60.7 vs 75.5, P < 0.001, and 60.7 vs 80.1, P < 0.001, respectively). The
      intervention group scored significantly higher than controls at sessions 2 and 3
      (75.5 vs 59.6, P = 0.009, and 80.1 vs 65.9, P = 0.019, respectively). The mean
      time (seconds) to complete the task was shorter for the intervention group than
      for controls during sessions 2 and 3 (217.4 vs 279.0, P = 0.004, and 201.4 vs
      261.9, P = 0.006, respectively). At the study conclusion, feedback subjects were
      more comfortable with robotic surgery than controls (90% vs 62%, P = 0.021) and
      expressed greater satisfaction with the learning experience (100% vs 67%, P =
      0.014). Of the intervention subjects, 85% found that peer feedback was useful and
      100% found it effective. CONCLUSIONS: Video-based peer feedback through social
      networking appears to be an effective paradigm for surgical education and
      accelerates the robotic surgery learning curve during simulation.

PMID- 24887971
TI  - The impact of functional dependency on outcomes after complex general and
      vascular surgery.
AB  - OBJECTIVE: To describe the outcomes of functionally dependent patients who
      undergo major general or vascular surgery and to determine the relationship
      between functional health status and early postoperative outcomes. BACKGROUND: In
      contrast to frailty, functional health status is a relatively easy entity to
      define and to measure and therefore may be a more practical variable to assess in
      patients who are being considered for major surgery. To date, few studies have
      assessed the impact of functional health status on surgical outcomes. METHODS:
      Patients undergoing 1 of 10 complex general or vascular operations were extracted
      from the 2005 to 2010 America College of Surgeons National Surgical Quality
      Improvement Program database. Propensity score techniques were used to match
      patients with and without preoperative functional dependency on known patient-
      and procedure-related factors. The postoperative outcomes of this matched cohort
      were then compared. RESULTS: A total of 10,246 functionally dependent surgical
      patients were included for analysis. These patients were more acutely and
      chronically ill than functionally independent patients, and they had higher rates
      of mortality and morbidity for each of the 10 procedures analyzed. Propensity
      matching techniques resulted in the creation of a cohort of functionally
      independent and dependent patients who were well matched for known patient- and
      procedure-related variables. Dependent patients from the matched cohort had a
      1.75-fold greater odds of postoperative death (95% confidence interval: 1.54
      1.98, P < 0.0001) than functionally independent patients. CONCLUSIONS:
      Preoperative functional dependency is an independent risk factor for mortality
      after major operation. Functional health status should be routinely assessed in
      patients who are being considered for complex surgery.

PMID- 24887972
TI  - Escalation of care in surgery: a systematic risk assessment to prevent avoidable
      harm in hospitalized patients.
AB  - OBJECTIVE: To systematically risk assess and analyze the escalation of care
      process in surgery so as to identify problems and provide recommendations for
      intervention. BACKGROUND: The ability to escalate care appropriately when
      managing deteriorating patients is a hallmark of surgical competence and safe
      postoperative care. Healthcare-Failure-Mode-Effects-Analysis (HFMEA) is a
      methodology adapted from safety-critical industries, which allows for hazardous
      process failures to be prospectively identified and solutions to be recommended.
      METHODS: Forty-two hours of ethnographic observations on surgical wards in 3
      London hospitals (phase 1) formed the basis of an escalation process diagram. A
      risk-assessment survey identified failures associated with process steps and
      attributed hazard scores (phase 2). Patient safety and clinical risk experts
      validated hazard scores through a group consensus meeting (phase 3). Hazardous
      failures were taken forward to multidisciplinary HFMEA where cause analysis was
      applied and interventions were recommended (phase 4). RESULTS: Observations
      identified 33 steps in the escalation process. The risk-assessment survey (30
      surgical staff members, 100% response) and expert consensus group identified 18
      hazardous failures associated with these steps. The HFMEA team identified 3
      adequately controlled failures; therefore, 15 were subjected to cause analysis.
      Outdated communication technology, understaffing, and hierarchical barriers were
      identified as root causes of failure. Participants recommended interventions
      based on these findings including defined escalation protocols, human factors
      education, enhanced communication technology, and improved clinical supervision.
      CONCLUSIONS: Failures in the escalation process amenable to intervention were
      systematically identified. This mapping of the escalation process will allow
      tailored interventions to enhance surgical training and patient safety.

PMID- 24887973
TI  - Colorectal Cancer Peritoneal Metastases: Second-look Laparotomy, Prophylactic
      HIPEC, or Both?

PMID- 24887974
TI  - Prophylaxis for Venous Thromboembolism After Laparoscopic Surgery for Colorectal
      Cancer: 1 Week or 4 Week?

PMID- 24887975
TI  - Reply to Letter: "A Randomized Prospective Multicenter Trial of
      Pancreaticoduodenectomy With and Without Routine Intraperitoneal Drainage".

PMID- 24887976
TI  - Reply to Letter: "What Ingredients Have You Used to Prepare This Delicious Lunch?
      A Critical Look Behind a Meta-analysis".

PMID- 24887977
TI  - Surgical coaching for individual performance improvement.

PMID- 24887978
TI  - Anatomical Liver Resections Guided by 3-Dimensional Parenchymal Staining Using
      Fusion Indocyanine Green Fluorescence Imaging.
AB  - OBJECTIVE: To investigate the feasibility and efficacy of anatomical liver
      resection (ALR) guided by fused images comprising a macroscopic view and
      indocyanine green fluorescence imaging (fusion IGFI). BACKGROUND: ALR is
      established in treating hepatocellular carcinoma or other malignancies to achieve
      curability and functional preservation. However, the conventional demarcation
      technique (CDT) marks only the organ surface and sometimes fails to execute a
      completely valid demarcation. METHODS: Twenty-four consecutive ALRs for focal
      liver malignancy were studied using fusion IGFI. Indocyanine green was
      administered systemically after selective inflow clamping in 12 patients or by
      portal puncture and direct injection in 12 patients, and we compared demarcation
      findings between fusion IGFI and CDT. The strength of contrast between target and
      nontarget areas was quantitatively calculated as contrast index and compared
      between IGFI and CDT according to injection technique or state of the liver
      surface. RESULTS: Fusion IGFI achieved valid demarcation in 23 of 24 patients
      (95.8%), whereas CDT achieved valid demarcation in only 10 patients (41.7%) (P <
      0.0001). The contrast index of fusion IGFI was 0.81 (0.18-2.51), which was
      significantly higher than that of CDT at 0.12 (0.01-0.42) (P < 0.0001), and the
      same result was obtained regardless of the injection method or liver surface
      state used. ALR was conducted referring to 3-dimensional staining of target
      parenchyma, with no related perioperative adverse events. CONCLUSIONS: Fusion
      IGFI is a safe imaging technique for ALR that attained valid 3-dimensional
      parenchymal demarcation with better feasibility and clearer demarcation than CDT.

PMID- 24887979
TI  - Reply to Letter: "Increasing the Interval Between Neoadjuvant Chemoradiotherapy
      and Surgery in Rectal Cancer: A Meta-analysis of Published Studies".

PMID- 24887980
TI  - Routine Drainage After Pancreaticoduodenectomy: Serum Amylase Can Guide Early,
      Selective Drain Removal.

PMID- 24887981
TI  - Geriatric Assessment as a Predictor of Delirium and Other Outcomes in Elderly
      Patients With Cancer.
AB  - OBJECTIVE: This study aimed to describe the implementation of preoperative
      geriatric assessment (GA) in patients undergoing major cancer surgery and to
      determine predictors of postoperative delirium. BACKGROUND: Geriatric surgical
      patients have unique vulnerabilities and are at increased risk of developing
      postoperative delirium. METHODS: Geriatricians at Memorial Sloan Kettering Cancer
      Center risk-stratify surgical patients with solid tumors, ages 75 years and
      older, using preoperative GA, which includes basic and instrumental activities of
      daily living (ADLs, IADLs), cognition (Mini-Cog test), history of falls,
      nutritional state, and comorbidities (Charlson Comorbidity Index). The Geriatrics
      Service evaluates patients for postoperative delirium using the confusion
      assessment method. A retrospective review was performed. The associations between
      GA and postoperative outcomes were evaluated. Univariate logistic regression
      analysis was performed to determine the predictive value of GA for postoperative
      delirium, and a multivariate model was built. RESULTS: In total, 416 patients who
      received preoperative evaluation by the Geriatrics Service between September 1,
      2010, and December 31, 2011, were included. Delirium occurred in 19% of patients.
      Patients with delirium had longer length of hospital stay (P < 0.001) and greater
      likelihood of discharge to a rehabilitation facility (P < 0.001). Charlson
      Comorbidity Index score, history of falls, dependent on IADL, and abnormal Mini
      Cog test results predicted postoperative delirium on univariate analysis.
      Developed using a stepwise selection method, a multivariate model to predict
      delirium is presented including Charlson Comorbidity Index score (P = 0.032),
      dependence IADLs (P = 0.011), and falls history (P = 0.056). CONCLUSIONS:
      Preoperative GA is feasible and may achieve a better understanding of older
      patients' perioperative risks, including delirium.

PMID- 24887983
TI  - Increasing the Interval Between Neoadjuvant Chemoradiotherapy and Surgery in
      Rectal Cancer.

PMID- 24887982
TI  - Cost and Mortality Associated With Postoperative Acute Kidney Injury.
AB  - OBJECTIVE: To determine the incremental hospital cost and mortality associated
      with the development of postoperative acute kidney injury (AKI) and with other
      associated postoperative complications. BACKGROUND: Each year 1.5 million
      patients develop a major complication after surgery. Postoperative AKI is one of
      the most common postoperative complications and is associated with an increase in
      hospital mortality and decreased survival for up to 15 years after surgery.
      METHODS: In a single-center cohort of 50,314 adult surgical patients undergoing
      major inpatient surgery, we applied risk-adjusted regression models for cost and
      mortality using postoperative AKI and other complications as the main independent
      predictors. We defined AKI using consensus Risk, Injury, Failure, Loss and End
      Stage Renal Disease criteria. RESULTS: The prevalence of AKI was 39% among 50,314
      patients with available serum creatinine. Patients with AKI were more likely to
      have postoperative complications and had longer lengths of stay in the intensive
      care unit and the hospital. The risk-adjusted average cost of care for patients
      undergoing surgery was $42,600 for patients with any AKI compared with $26,700
      for patients without AKI. The risk-adjusted 90-day mortality was 6.5% for
      patients with any AKI compared with 4.4% for patients without AKI. Serious
      postoperative complications resulted in increased cost of care and mortality for
      all patients, but the increase was much larger for those patients with any degree
      of AKI. CONCLUSIONS: Hospital costs and mortality are strongly associated with
      postoperative AKI, are correlated with the severity of AKI, and are much higher
      for patients with other postoperative complications in addition to AKI.

PMID- 24887984
TI  - Medicare's Hospital Readmissions Reduction Program in Surgery May
      Disproportionately Affect Minority-serving Hospitals.
AB  - OBJECTIVE: To project readmission penalties for hospitals performing cardiac
      surgery and examine how these penalties will affect minority-serving hospitals.
      BACKGROUND: The Hospital Readmissions Reduction Program will potentially expand
      penalties for higher-than-predicted readmission rates to cardiac procedures in
      the near future. The impact of these penalties on minority-serving hospitals is
      unknown. METHODS: We examined national Medicare beneficiaries undergoing coronary
      artery bypass grafting in 2008 to 2010 (N = 255,250 patients, 1186 hospitals).
      Using hierarchical logistic regression, we calculated hospital observed-to
      expected readmission ratios. Hospital penalties were projected according to the
      Hospital Readmissions Reduction Program formula using only coronary artery bypass
      grafting readmissions with a 3% maximum penalty of total Medicare revenue.
      Hospitals were classified into quintiles according to proportion of black
      patients treated. Minority-serving hospitals were defined as hospitals in the top
      quintile whereas non-minority-serving hospitals were those in the bottom
      quintile. Projected readmission penalties were compared across quintiles.
      RESULTS: Forty-seven percent of hospitals (559 of 1186) were projected to be
      assessed a penalty. Twenty-eight percent of hospitals (330 of 1186) would be
      penalized less than 1% of total Medicare revenue whereas 5% of hospitals (55 of
      1186) would receive the maximum 3% penalty. Minority-serving hospitals were
      almost twice as likely to be penalized than non-minority-serving hospitals (61%
      vs 32%) and were projected almost triple the reductions in reimbursement ($112
      million vs $41 million). CONCLUSIONS: Minority-serving hospitals would
      disproportionately bear the burden of readmission penalties if expanded to
      include cardiac surgery. Given these hospitals' narrow profit margins,
      readmission penalties may have a profound impact on these hospitals' ability to
      care for disadvantaged patients.

PMID- 24887985
TI  - Patient satisfaction and quality of surgical care in US hospitals.
AB  - OBJECTIVE: The relationship between patient satisfaction and surgical quality is
      unclear for US hospitals. Using national data, we examined if hospitals with high
      patient satisfaction have lower levels of performance on accepted measures of the
      quality and efficiency of surgical care. BACKGROUND: Federal policymakers have
      made patient satisfaction a core measure for the way hospitals are evaluated and
      paid through the value-based purchasing program. There is broad concern that
      performance on patient satisfaction may have little or even a negative
      correlation with the quality of surgical care, leading to potential trade-offs in
      efforts to improve patient experience with other surgical quality measures.
      METHODS: We used the Hospital Consumer Assessment of Healthcare Providers and
      Systems survey data from 2010 and 2011 to assess performance on patient
      experience. We used national Medicare data on 6 common surgical procedures to
      calculate measures of surgical efficiency and quality: risk-adjusted length of
      stay, process score, risk-adjusted mortality rate, risk-adjusted readmission
      rate, and a composite z score across all 4 metrics. Multivariate models adjusting
      for hospital characteristics were used to assess the independent relationships
      between patient satisfaction and measures of surgical efficiency and quality.
      RESULTS: Of the 2953 US hospitals that perform one of these 6 procedures, the
      median patient satisfaction score was 69.5% (interquartile range, 63%-75.5%).
      Length of stay was shorter in hospitals with the highest levels of patient
      satisfaction (7.1 days vs 7.7 days, P < 0.001). Adjusting for procedural volume
      and structural characteristics, institutions in the highest quartile of patient
      satisfaction had the higher process of care performance (96.5 vs 95.5, P <
      0.001), lower readmission rates (12.3% vs 13.6%, P < 0.001), and lower mortality
      (3.1% vs 3.6%) than those in the lowest quartile. Hospitals with high patient
      satisfaction also had a higher composite score for quality across all measures (P
      < 0.001). CONCLUSIONS: Among US hospitals that perform major surgical procedures,
      hospitals with high patient satisfaction provided more efficient care and were
      associated with higher surgical quality. Our findings suggest there need not be a
      trade-off between good quality of care for surgical patients and ensuring a
      positive patient experience.

PMID- 24887986
TI  - Treatment of Hymenoptera venom allergy: an update.
AB  - PURPOSE OF REVIEW: To review and summarize the studies published between 2012 and
      2014 about the use of venom immunotherapy (VIT) to treat Hymenoptera
      hypersensitivity. RECENT FINDINGS: Several studies reconfirm the effectiveness of
      VIT in both children and adults, and provide a better understanding of its immune
      modulating effects. There are concerns about its cost-effectiveness; however, VIT
      versus self-injectable epinephrine alone when stung is the preferred treatment of
      choice for affected individuals when quality-of-life issues are considered.
      Ultrarush VIT may be as effective in children as in adults but is associated with
      a high risk of systemic allergic reactions (SARs). Controversy continues about
      the use of angiotensin-converting enzyme inhibitors and their potential for
      increased SARs while on VIT. Individuals with mast cell disorders, female sex,
      honeybee allergy, and those receiving rush or ultrarush VITs are at higher risk
      for SARs. Elevated baseline serum tryptase levels greater than 20 MUg/l, SARs
      during VIT, and honeybee sensitivity are risk factors for VIT failure. SUMMARY:
      VIT remains the gold standard to treat Hymenoptera-allergic individuals to
      prevent future sting-induced SARs in both children and adults.

PMID- 24887987
TI  - Managing type 2 diabetes mellitus across the disease spectrum.

PMID- 24887989
TI  - [Introduction: full consciousness and psychiatry].

PMID- 24887988
TI  - Dr Amit Rai responds.

PMID- 24887991
TI  - Taking to the streets.

PMID- 24887990
TI  - Robert Koch (1843-1910) and dermatology on his  171st birthday.
AB  - Robert Koch (1843-1910) received the Nobel Prize in Medicine in 1905 for his
      studies of tuberculosis. He contributed significantly to microbiology, isolating
      also cholera and anthrax pathogens, and introducing several postulates in this
      field. In addition, he developed staining methods, as well as culturing and
      microscopic techniques. Many of his achievements have also influenced
      dermatology. This contribution reviews his life and major achievements on the
      occasion of the 171st anniversary of his birth.

PMID- 24887993
TI  - Bereavement care.

PMID- 24887992
TI  - Attending courses and conferences without breaking the bank.

PMID- 24887994
TI  - Iates show a new age of motherhood.

PMID- 24887995
TI  - Next pregnancy won't always bring comfort after loss.

PMID- 24887996
TI  - No room for complacency.

PMID- 24887997
TI  - More than a midwife.

PMID- 24887998
TI  - A delicate balance.

PMID- 24887999
TI  - Induction versus expectant monitoring for IUGR.

PMID- 24888000
TI  - How to ... administer Entonox.

PMID- 24888001
TI  - Feeling right at home.

PMID- 24888002
TI  - With a little help from our friends.

PMID- 24888003
TI  - Won't you stay the night.

PMID- 24888004
TI  - The right to raise concerns.

PMID- 24888006
TI  - Success in the city.

PMID- 24888005
TI  - A fight for funding.

PMID- 24888007
TI  - Let's get back to normality.

PMID- 24888008
TI  - A day in the life of ... a strategic lead of maternity and newborn services.

PMID- 24888009
TI  - The power rests with you...

PMID- 24888010
TI  - Capacity remains a concern at Milton Keynes hospital.

PMID- 24888011
TI  - Are midwives becoming too specialised?

PMID- 24888012
TI  - End of the road.

PMID- 24888013
TI  - The fear of childbirth.

PMID- 24888014
TI  - Improved care for Polish women.

PMID- 24888015
TI  - Specialised versus generalised.

PMID- 24888016
TI  - Uniformed?

PMID- 24888017
TI  - Pregnancy-associated breast cancer.

PMID- 24888018
TI  - How to ... measure a mother's pulse/heart rate.

PMID- 24888020
TI  - Governance Committee Governance review: transforming the RCM.

PMID- 24888021
TI  - The future of the profession.

PMID- 24888022
TI  - Which band am I?

PMID- 24888023
TI  - So you want to be an expert witness....

PMID- 24888024
TI  - There will be blood.

PMID- 24888025
TI  - It's more than just talking.

PMID- 24888027
TI  - Supporting representatives to support members.

PMID- 24888026
TI  - The issues unearthed.

PMID- 24888028
TI  - Stepping stones to the future.

PMID- 24888029
TI  - Avoiding troubled waters.

PMID- 24888030
TI  - Bridging the gap?

PMID- 24888031
TI  - Why did this happen?

PMID- 24888032
TI  - A growing problem.

PMID- 24888033
TI  - A healthier Start4Life.

PMID- 24888034
TI  - Craving to quit.

PMID- 24888036
TI  - A day in the life of ... a midwife sonographer.

PMID- 24888037
TI  - Why not? You've got nothing to lose.

PMID- 24888038
TI  - NHS faces major shake-up.

PMID- 24888035
TI  - A moment to reflect.

PMID- 24888039
TI  - Neonatal services in Wales 'understaffed'.

PMID- 24888040
TI  - Effects of baby boom in the over 40s.

PMID- 24888041
TI  - Single umbilical artery and IUGR.

PMID- 24888042
TI  - Unapologetically old school.

PMID- 24888043
TI  - Case contents for nursing home.

PMID- 24888044
TI  - Formula milk company sponsorship.

PMID- 24888045
TI  - Stepford midwives.

PMID- 24888046
TI  - It's a stressful world.

PMID- 24888047
TI  - Challenging the status quo.

PMID- 24888048
TI  - How to ... measure a baby's respiratory rate.

PMID- 24888049
TI  - Governance Committee modern governance for the RCM: the Council's strategy.

PMID- 24888050
TI  - Clinic complexities.

PMID- 24888051
TI  - Be the apprentice.

PMID- 24888052
TI  - Changes to midwives exemptions.

PMID- 24888053
TI  - A father's hidden despair.

PMID- 24888054
TI  - A green light for improved resuscitation.

PMID- 24888055
TI  - Seizing control.

PMID- 24888056
TI  - Visualise and measure.

PMID- 24888058
TI  - A day in the life of ... a female genital mutilation/public health specialist.

PMID- 24888057
TI  - Learning on the job.

PMID- 24888059
TI  - 'I asked the mother...'.

PMID- 24888060
TI  - More guidelines for obese pregnant women.

PMID- 24888061
TI  - Mixing alcohol and pregnancy.

PMID- 24888062
TI  - Advancement of obstetrics or murder?

PMID- 24888063
TI  - Community midwifery.

PMID- 24888064
TI  - Nurse/midwife.

PMID- 24888065
TI  - Pre-conceptual care.

PMID- 24888066
TI  - Measurement of postpartum blood loss.

PMID- 24888067
TI  - How to ... measure a baby's heart rate.

PMID- 24888068
TI  - Speak up ... all politicians are listening.

PMID- 24888069
TI  - Your opinions matter.

PMID- 24888070
TI  - So your baby has Down's syndrome.

PMID- 24888071
TI  - 3 steps to success.

PMID- 24888072
TI  - One born every minute ... how it was for us.

PMID- 24888073
TI  - The world needs midwives now more than ever.

PMID- 24888074
TI  - It's a real time emergency.

PMID- 24888075
TI  - A well-rounded approach.

PMID- 24888076
TI  - The 'natural caesarean'.

PMID- 24888077
TI  - Naked below the elbow.

PMID- 24888078
TI  - When blood doesn't clot.

PMID- 24888079
TI  - The climb to the top.

PMID- 24888080
TI  - Degree challenges.

PMID- 24888081
TI  - Remembering times past.

PMID- 24888083
TI  - Format change, Facebook and fundraising!

PMID- 24888084
TI  - A day in the life of ... a specialist perineal midwife.

PMID- 24888082
TI  - What do women think?

PMID- 24888085
TI  - Maternity is still top of the bill.

PMID- 24888086
TI  - Pregnant women lacking vitamin D.

PMID- 24888087
TI  - 'Little evidence' to show acupuncture diminishes the pain of childbirth.

PMID- 24888088
TI  - Controversies in cot deaths.

PMID- 24888089
TI  - A dying breed.

PMID- 24888090
TI  - FAS info.

PMID- 24888091
TI  - Ginger.

PMID- 24888092
TI  - Who's looking after the boys?

PMID- 24888093
TI  - Infant-feeding practices after opening a human milk bank.

PMID- 24888094
TI  - How to ... measure a mother's respiratory rate.

PMID- 24888096
TI  - Mirror, mirror, on the wall....

PMID- 24888095
TI  - Exciting political times ahead.

PMID- 24888097
TI  - Not enough helping hands.

PMID- 24888098
TI  - Keeping it cool.

PMID- 24888099
TI  - It's time for Maternity Action.

PMID- 24888100
TI  - Is it bullying or just being bossy?

PMID- 24888101
TI  - Room for improvement.

PMID- 24888102
TI  - A deadly itch.

PMID- 24888103
TI  - A paucity of platelets.

PMID- 24888104
TI  - Building a bridge between cultures.

PMID- 24888105
TI  - A new body on the block.

PMID- 24888106
TI  - Who cares when you lose a baby?

PMID- 24888107
TI  - A push for change.

PMID- 24888108
TI  - Back to work with the RCM.

PMID- 24888109
TI  - A day in the life of ... the RCM deputy general secretary.

PMID- 24888110
TI  - Sharing support and inspiration.

PMID- 24888111
TI  - New mothers feel let down, says NCT report.

PMID- 24888112
TI  - Midwifery 2020: what's new?

PMID- 24888113
TI  - Radio active.

PMID- 24888114
TI  - Complementary and alternative drugs.

PMID- 24888115
TI  - How to ... administer drugs.

PMID- 24888116
TI  - It's all go at Tommy's.

PMID- 24888117
TI  - Reaching out.

PMID- 24888118
TI  - When times are tough....

PMID- 24888119
TI  - Call to action.

PMID- 24888121
TI  - Lifelong learning.

PMID- 24888120
TI  - Development and clarity for all.

PMID- 24888123
TI  - Spread the word.

PMID- 24888122
TI  - Vaccinate to eliminate.

PMID- 24888124
TI  - A day in the life of ... a membership services officer at the RCM.

PMID- 24888125
TI  - Regeneration and renewal.

PMID- 24888126
TI  - Leaving midwifery.

PMID- 24888128
TI  - Midwives ask, is the government listening?

PMID- 24888127
TI  - Hypnobirthing or natal hypnotherapy?

PMID- 24888129
TI  - Figures reveal drop in home birth rate.

PMID- 24888130
TI  - More input for a growing problem.

PMID- 24888131
TI  - Out on her own.

PMID- 24888133
TI  - Caesarean section rates across English trusts.

PMID- 24888132
TI  - Care after miscarriage.

PMID- 24888134
TI  - How to ... administer oral medication.

PMID- 24888136
TI  - Scratching the surface.

PMID- 24888135
TI  - Somebody to lean on.

PMID- 24888137
TI  - Show of strength.

PMID- 24888138
TI  - A call to arms.

PMID- 24888139
TI  - Knowledge is power.

PMID- 24888140
TI  - Learning to lessen risk.

PMID- 24888141
TI  - Creating memories.

PMID- 24888142
TI  - Right to life.

PMID- 24888143
TI  - Keep calm and carry on!

PMID- 24888144
TI  - A day in the ljfe of ... a professor of midwifery.

PMID- 24888146
TI  - Supervised practice.

PMID- 24888145
TI  - What does 2011 hold for the RCM?

PMID- 24888147
TI  - Care after miscarriage.

PMID- 24888148
TI  - Investigation reveals desperation on wards.

PMID- 24888149
TI  - RCOG president: care from the night shift is not as good.

PMID- 24888150
TI  - Breast is best ... until when?

PMID- 24888151
TI  - Africa afresh.

PMID- 24888152
TI  - Expectations and experiences of posnatal care.

PMID- 24888154
TI  - RCM Annual Midwifery Awards 2011. Inspired choices.

PMID- 24888153
TI  - How to ... administer intramuscular medication.

PMID- 24888155
TI  - One-stop shop.

PMID- 24888156
TI  - Revisit and revise.

PMID- 24888157
TI  - Learning is just a click away.

PMID- 24888158
TI  - From MSW to midwife.

PMID- 24888159
TI  - More hand-holding, less arm-twisting.

PMID- 24888160
TI  - Taking the lead.

PMID- 24888161
TI  - A day in the life of ... a head of midwifery.

PMID- 24888162
TI  - Vision and drive in abundance.

PMID- 24888163
TI  - New NICE guidance on tackling hypertension.

PMID- 24888164
TI  - CCTV expertise to prevent stillbirths.

PMID- 24888165
TI  - Home births: midwives versus doctors?

PMID- 24888166
TI  - Look out for the limitations.

PMID- 24888168
TI  - TBAs.

PMID- 24888167
TI  - Enter the 'Midwifery Oscars'.

PMID- 24888169
TI  - Abandoned babies--your experience?

PMID- 24888170
TI  - NHS Direct.

PMID- 24888172
TI  - Shaping up while pregnant.

PMID- 24888173
TI  - The use of a chaperone.

PMID- 24888175
TI  - The road ahead.

PMID- 24888174
TI  - How to ... prevent. pressure sores.

PMID- 24888177
TI  - What it means to win....

PMID- 24888176
TI  - It's a weighty issue.

PMID- 24888178
TI  - Too much or too little?

PMID- 24888179
TI  - Towards normality--a vision for supervision.

PMID- 24888180
TI  - Respiratory distress.

PMID- 24888181
TI  - A beautiful pregnancy.

PMID- 24888182
TI  - 12 months later....

PMID- 24888183
TI  - Going to yuor nappy place.

PMID- 24888184
TI  - A day in the life of ... a lead midwife adviser at the NMC.

PMID- 24888186
TI  - Incorporation of ligand-receptor binding-site models and transistor-based sensors
      for resolving dissociation constants and number of binding sites.
AB  - Ligand-receptor binding site model is used to elucidate the binding affinity
      between ligands and receptors, with transistor-based sensors. AlGaN/GaN high
      electron mobility transistors (HEMTs) were immobilised with antibodies and human
      immunodeficiency virus type 1 reverse transcriptase enzymes to detect peptides
      and human immunodeficiency virus drugs, respectively. The signals generated by
      the sensors because of the binding of the ligands to the receptors were fitted
      into the binding-site models and analysed. The dissociation constants of the
      ligand-receptor pairs and the number of the binding sites on the receptors were
      revealed. The results are very consistent with the data reported by the other
      methods from the literatures. The incorporation of the HEMTs and the binding-site
      models is demonstrated to be useful for studying the mechanism of the
      biomolecular interaction and the application for quick and cost-effective drug
      developments.

PMID- 24888185
TI  - Spatially selective release of aptamer-captured cells by temperature mediation.
AB  - Isolation of cells from heterogeneous biological samples is critical in both
      basic biological research and clinical diagnostics. Affinity-based methods, such
      as those that recognise cells by binding antibodies to cell membrane biomarkers,
      can be used to achieve specific cell isolation. Microfluidic techniques have been
      employed to achieve more efficient and effective cell isolation. By employing
      aptamers as surface-immobilised ligands, cells can be easily released and
      collected after specific capture. However, these methods still have limitations
      in cell release efficiency and spatial selectivity. This study presents an
      aptamer-based microfluidic device that not only achieves specific affinity cell
      capture, but also enables spatially selective temperature-mediated release and
      retrieval of cells without detectable damage. The specific cell capture is
      realised by using surface-patterned aptamers in a microchamber on a temperature
      control chip. Spatially selective cell release is achieved by utilising a group
      of microheater and temperature sensor that restricts temperature changes, and
      therefore the disruption of cell-aptamer interactions, to a design-specified
      region. Experimental results with CCRF-CEM cells and sgc8c aptamers have
      demonstrated the specific cell capture and temperature-mediated release of
      selected groups of cells with negligible disruption to their viability.

PMID- 24888187
TI  - Specific interactions between functionalised particles and circulating tumour
      cells.
AB  - Receptor-ligand binding has been one of the more popular approaches to
      specifically targeting tumour cells. In this work, targeting efficiency was
      quantitatively characterized using silica particles functionalized with EpCAM
      antibodies and EpCAM-expressing BT-20 breast cancer cells. The effects of
      incubation time and particle concentration on the number of functionalised
      particles bound to target cells were experimentally investigated. The number of
      bound particles was found to increase with particle concentration, but not
      necessarily with incubation time. Binding affinity loss because of cell-particle
      cell interaction was identified as a limiting mechanism for the number of
      particles bound to target cells. While cell-surface coverage because of bound
      particles rises exponentially under low particle concentration, it features a
      peak value at high particle concentration. The current findings suggest that
      separation of a bound particle from a cell may be detrimental to cellular binding
      affinity.

PMID- 24888188
TI  - Use of cell morphology as early bioindicator for viral infection.
AB  - This study reports a correlation between cellular morphology and the ability of
      adapting to vesicular stomatitis virus infection. A time-lapse approach was
      employed to track the individual difference between homologous cells in adapting
      to viral infection. The authors single-cell analysis indicates that upon viral
      infection, mature cells that are in spindle shape are less likely to be infected
      after 24 h infection. On the other hand, cells undergoing proliferation, which
      are in rounder shape, tend to adopt a much higher viral infection within the same
      amount of time. This fact suggests that cellular morphology may be an early
      bioindicator for viral infection. The findings in this study could potentially be
      applied to other viral infection models.

PMID- 24888189
TI  - Electrochemical microsensor based on gold nanoparticles modified electrode for
      total phosphorus determinations in water.
AB  - This work mainly describes an electrochemical microsensor based on the reduction
      of molybdophosphate complex for total phosphorus (TP) determinations in water.
      The microelectrode was fabricated using microelectromechanical systems (MEMS)
      techniques and porous, branching gold nanoparticles (AuNPs) were electrodeposited
      on the microelectrode to improve its sensitivity. Calibration of the microsensor
      was performed with standard phosphate solutions prepared with KH2PO4 with pH
      adjusted to 1.0. The experimental results showed that both sensitivity and
      current response are improved effectively using this modified microelectrodes:
      The limit of detection of the microsensor is 1.2 x 10(-7) mol/l and linear range
      is 3 x 10(-7) to 3 x 10(-4) mol/l. The sensitivity of unmodified electrode is 
      0.27nA/micromol x 1(-1) (R2 = 0.994), whereas the sensitivity of AuNPs modified
      electrode is -0.89 nA/micromol 1(-1) (R2 = 0.8). The current response of modified
      electrode is 6 times larger than that of unmodified electrode in average.
      Detection of TP was also carried out with digested TP standard solutions for both
      modified and unmodified electrodes, and results were consistent with the nominal
      value of phosphorus concentration. This microsensor provides the probability of
      combining TP detection device with micro-digesting device to form a TP detection
      system, which can realise the automotive and on-line monitoring of TP in surface
      water.

PMID- 24888190
TI  - Cantilever arrayed blood pressure sensor for arterial applanation tonometry.
AB  - The authors developed a cantilever-arrayed blood pressure sensor array fabricated
      by (111) silicon bulk-micromachining for the non-invasive and continuous
      measurement of blood pressure. The blood pressure sensor measures the blood
      pressure based on the change in the resistance of the piezoresistor on a 5-microm
      thick-arrayed perforated membrane and 20-microm-thick metal pads. The length and
      the width of the unit membrane are 210 and 310 microm, respectively. The width of
      the insensible zone between the adjacent units is only 10 microm. The resistance
      change over contact force was measured to verify the performance. The good
      linearity of the result confirmed that the polydimethylsiloxane package transfers
      the forces appropriately. The measured sensitivity was about 4.5%/N. The maximum
      measurement range and the resolution of the fabricated blood pressure sensor were
      greater than 900 mmHg (= 120 kPa) and less than 1 mmHg (= 133.3 Pa),
      respectively.

PMID- 24888191
TI  - Carbon nanotube-based hot-film and temperature sensor assembled by optically
      induced dielectrophoresis.
AB  - The development of carbon nanotube (CNT)-based sensors remains an active area of
      research. Towards this end, a new method for manipulating CNTs, assembling CNT
      networks and fabricating CNT-based nanosensors was demonstrated in this study.
      CNTs were collected and concentrated by optically-induced dielectrophoresis
      (ODEP) forces and aligned between a pair of electrodes. This assembly was then
      used directly as a temperature sensor and a hot-film anemometer, which detects
      changes in windspeed. By offering efficient CNT collection and ready-to-use
      sensor fabrication, this ODEP-based approach presents a promising method for the
      development of CNT-based sensing applications and massively parallel assembly of
      CNT-lines. The developed CNT-based nanosensors may be used to measure the
      temperature and the flow velocity of bio-samples in the near future.

PMID- 24888192
TI  - Effect of molecular structure of sulphonated polyimide membranes on water
      sorption.
AB  - Water sorption in sulphonated polyimides with or without ionic block structure
      was analysed with Feng's new dual mode model. The effect of their molecular
      structure that determines the chain organisation in the solid materials was
      analysed by using the model parameters. The model parameters Cp and A' correspond
      to the sorbed water molecules on the first layer close to the ionic groups and on
      the subsequent layers, respectively. Based on these fitted physical parameters,
      the water sorption on the membranes with different counterions was studied and
      the hydration energy was proved to have much influence on the Cp values. The
      effect of the structure of the block and the random copolymers on the Cp and A'
      values was discussed and compared with that for the well-known Nafion membranes.
      The large amount of sorbed water at high activities may induce a sufficiently
      large mobility of the polymer segments in the hydrophilic domains for material
      inflation, which leads to high A' values.

PMID- 24888193
TI  - [Effect of 6-month therapy with perindopril A on structural-functional state of
      arterial vascular bed in patients with chronic heart failure].
AB  - In patients with chronic heart failure (CHF) endothelial dysfunction of large
      vessels is an independent predictor of repeated hospitalizations because of CHF
      aggravation and cardiac death. OBJECTIVE: To evaluate the effect of perindopril A
      (5-10 mg/day) on endothelial function of large vessels in patients with CHF.
      MATERIAL AND METHODS: The study included 30 patients with NYHA class II-III CHF
      aged 45-70 years. Patients took perindopril A 5-10 mg for 6 months. Patients
      underwent 24-h BP monitoring, assessment of endothelium vasodilation. RESULTS: In
      the end of period of treatment hypotensive effect and improvement of endothelial
      function of large vessels were achieved. We observed increase of flow-mediated
      vasodilation (FMD) measured by high-frequency ultrasound of brachial artery after
      reactive hyperemia: FMD1 4.25 (3.9; 4.8) vs FMD2 6.8 (5.1; 7.4), p = 0.003) and
      enhancement of pulse wave amplitude estimated by photoplethysmography (shear
      phase - SF): SF1 6.62 (2.4; 8.7) vs SF2 7.36 (3.8; 10.2) (p = 0.003).

PMID- 24888194
TI  - [Comparison pharmacoeconomics organoprotection using fixed combinations of
      antihypertensive drugs].

PMID- 24888195
TI  - [Risk factors of development of hypertension and metabolic abnormalities in
      practically healthy].
AB  - In a group of 492 apparently healthy working men (mean aged 55 years) we measured
      body mass index (BMI), and assessed states of lipid, carbohydrate and purine
      metabolism, morphological and functional state of cardiovascular system (by
      transthoracic echocardiography), thickness of intima-media complex of common
      carotid artery (by ultrasound examination of brachiocephalic arteries). SCORE
      tables were used for calculation of 10 year risk of fatal heart disease. Most
      frequent findings were excessive weight (n = 306, 62.2%) and I-II degree obesity
      (n = 105, 21.34%). Most subjects had elevated level of total cholesterol (n =
      323, 65.65%) or low density lipoprotein cholesterol > 3 mmol/l (n = 369, 75.93%).
      There was significant difference in levels of uric acid between groups of
      subjects with a BMI < 25 and > 30 kg/m2 (p = 0.00). About one third of men had
      arterial hypertension. Portion of subjects with grade 1-2 hypertension was
      significantly higher among persons with BMI above 25 kg/m2. Transthoracic
      echocardiography showed that increase in BMI was significantly associated with
      increased left atrial and aortic diameters and thicknesses of left ventricular
      posterior wall and ventricular septum (p = 0.00) although cardiac contractility
      and diastolic function were not compromised.

PMID- 24888196
TI  - [Prevalence and risk factors of extra-coronary artery disease in patients with
      diabetes which confirmed atherosclerosis of coronary arteries].
AB  - AIM: To assess prevalence and risk factors of extra-coronary artery disease
      (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic
      arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2)
      diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries
      (CA). MATERIAL: 100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with
      hemodynamically significant atherosclerosis of CA confirmed by coronary
      angiography. METHODS: All patients underwent duplex ultrasonography of PA LE,
      BCA, RA. Other studies included assessment of clinical characteristics and
      measurement of the following parameters: profibrogenic cytokines (transforming
      growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte
      chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed
      and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor
      [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular
      cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1
      [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine
      [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP),
      fibroblast growth factor 23 (FGF-23), and fibrinogen. RESULTS: Portions of P with
      multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5,
      WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was
      identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and
      11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of
      profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI
      I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P
      with diabetes and multifocal atherosclerosis demonstrated significant increases
      of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR
      compared with P with atherosclerosis in 1 vascular bed. Logistic regression model
      identified diabetes, reduced renal function, previous myocardial infarction,
      smoking, ADMA and fibrinogen as factors associated with presence of multifocal
      atherosclerosis. CONCLUSION: Coexistence of atherosclerosis in two or more
      vascular beds was more frequent in P with diabetes and hemodynamically
      significant CA atherosclerosis than in PWD. It was associated with renal and
      cardiac dysfunction, excessive activation of mediators of inflammation,
      hemostasis, and factors of endothelial damage.

PMID- 24888198
TI  - [Brachial artery endothelial function in teenagers with obesity depending on
      severity of clinical, trophological and metabolic disorders].
AB  - We carried out complex examination of 68 adolescents aged 11-17 years with
      primary obesity which in addition to assessment of clinical-anamnestic,
      laboratory data and functional parameters of cardiovascular system included
      registration of reaction of brachial artery endothelium to reactive hyperemia.
      Vascular endothelial dysfunction (VED) was found in 66% of obese teenagers.
      Obesity in adolescents with VED was characterized by aggravated course with
      higher fat mass index (36.8 +/- 4.39%) and prevalence of hypothalamic (42%) and
      metabolic (8.8%) syndromes. Stable arterial hypertension (AH) found in 37% of
      examined adolescents was 1.5 times more often registered in those with VED. We
      distinguished 4 groups of adolescents with various degree of risk of development
      of cardiovascular disorders: with stable AH and VED (group I), with stable AH and
      normal function of vascular endothelium (group II), with normal or labile
      arterial pressure with VED (group III), with normal or labile arterial pressure
      with normal function of vascular endothelium. It is expedient to supplement
      examination of obese adolescents with assessment of the state of vascular
      endothelium aiming at determination of degree of risk of development of
      atherosclerosis and/or stable AH.

PMID- 24888197
TI  - [Predictors of survival after heart transplantation: role of pretransplantation
      and posttransplantation factors].
AB  - Objective of this study was to assess the impact of pre- and posttransplantation
      factors on 12-month survival after orthotopic heart transplantation (OHT). Annual
      survival after OHT was 79.2%. The following factors were significantly negatively
      associated with annual survival: recipient's serum C-reactive protein (CRP) > or
      = 11.5 mg/ml prior to donor heart transplant (odds ratio [OR] 5.74, p = 0.011)
      and infectious complications after OHT (OR = 4.80, p = 0.009). Recipient's high
      CRP level was associated with mortality due to infectious complications (r(pb) =
      0.47, p = 0.006), elevated troponin I concentrations (r(s) = 0.44, p = 0.012),
      and impaired hemodynamics of both recipient's heart and graft: right ventricular
      (RV) end diastolic area (EDA) prior to OHT (r(s) = 0.41, p = 0.015), elevated
      pulmonary artery pressure (PAP) (r(s) = 0.36, p < 0.001), and decreased left
      ventricular ejection fraction (LVEF) (r(s) = -0.45, p < 0.001) of the
      transplanted heart. Hearts of those who died after OHT irrespective of cause of
      death were characterized by more severe right heart dilation as evidenced by
      statistically significant increase of median RV EDA prior to OHT. After heart
      transplantation in those who later died decreased RV contractility was
      accompanied with elevation of PAP and decrease of LVEF. Acute graft rejection
      events 71.4% of which occurred in patients younger than 30 years had no influence
      on survival during 12 months after OHT. Other factors not associated with 12
      months survival were donor and recipient age, pretransplant pathology, patient's
      UNOS status, graft ischemia duration, artificial circulatory support and
      preexistent surgical interventions. Development of diabetes mellitus in
      posttransplantation period, arterial hypertension and sinus node dysfunction
      requiring permanent pacing also were not identified as factors affecting 1 year
      survival after OTH.

PMID- 24888199
TI  - [Dose-dependent effect of atorvastatin on erectile function and androgen status
      in men with high cardiovascular risk].
AB  - The purpose of this study was to evaluate the influence of three different doses
      of atorvastatin on erectile function and androgen status in men with high risk of
      cardiovascular disease (CVD). In an open randomized comparative study with
      parallel groups of 24 weeks were included 100 men aged 40 to 59 years with high
      risk of CVD, dyslipidemia and metabolic disorders. All patients underwent
      measurement of blood pressure, anthropometric and biochemical parameters: total
      cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low density
      lipoprotein (LDL). Erectile function was assessed using a questionnaire of the
      International Index of Erectile Function. Study of androgen status included
      clinical evaluation of androgen deficiency using the standard international
      questionnaire "Questionnaire symptoms age men."All study participants were
      randomly assigned to 4 groups: group 1 (n = 28) was treated with atorvastatin 10
      mg, group 2--I (n = 27)--20 mg, group 3 (n = 28)--40 mg/day and 4th control group
      (n = 30) did not receive atorvastatin. Patients were assessed and examined after
      1, 3 and 6 months. The therapy indicated a dose-dependent decrease in the levels
      of total cholesterol and LDL cholesterol. In all cases, the concentration of HDL
      cholesterol increased by an average of 10%. Increasing the dose of atorvastatin
      was associated with a more pronounced reduction in triglycerides in the blood.
      Lipid-lowering therapy with atorvastatin at higher doses has been associated with
      a slight (8%), but statistically significant decrease in androgen erectile
      function and status (10%) of the male reproductive age with a high risk of
      developing CVD. Concluded that the dose of atorvastatin should be individualized
      according to the level of total cardiovascular risk. With increasing doses of
      atorvastatin its metabolic effects must be considered and in patients with high
      risk of developing CVD and with some comorbidities (carbohydrate metabolism
      disorders, erectile dysfunction).

PMID- 24888200
TI  - [Third generation calcium antagonist lercanidipine: the evidence base for
      clinical decision].

PMID- 24888201
TI  - [Slowing of the heart rate. Why, how and how much--we all know about the
      problem?].

PMID- 24888202
TI  - [Purine receptors and associated signaling systems in regulation of platelet
      function].
AB  - Purine receptors of platelets play key role in hemostasis and thrombogenesis and
      they are used as targets for antiplatelet therapy. Platelets express three
      subtypes of purine receptors--P2X1, P2Y1 and P2Y12. The expression, ligands and
      sensitivity of purine receptors of platelets and their role in thrombogenesis are
      discussed in this article. Authors debate information about basic molecular
      mechanisms, links with intracellular signaling and biological effects of purine
      receptors activation. In conclusion, understanding of signaling mechanisms of
      purine receptors is a basis for further pharmacological strategy and effective
      antiplatelet therapy development.

PMID- 24888203
TI  - [Left bundle branch block: from anatomy to prognostic value].

PMID- 24888204
TI  - [Antiarrhythmic therapy in patients with paroxysmal and persistent atrial
      fibrillation: identification of achievable goals and assessment of available
      funds].
AB  - One of the achievable goals of treatment of patients with paroxysmal and
      persistent atrial fibrillation should be to prevent the progression to permanent
      form of arrhythmia, which is associated with an increased risk of complications
      and worsening prognosis. The review presents easily identifiable predictors of
      progression of atrial fibrillation, reviews the available treatment options and
      their effectiveness and safety.

PMID- 24888205
TI  - [Effect of design of standard metallic stents on neointimal hyperplasia and
      restenosis].
AB  - Coronary stents became an integral part of treatment of ischemic heart disease
      (IHD). Number of percutaneous coronary interventions (PCI) in patients with IHD
      in Russia constantly growing. At a certain stage of development of interventional
      cardiology drug eluting stents (DES) were created and became actively used.
      Compared with metallic stents (MS) drug eluting stents allow to substantially
      reduce risk of restenosis. However DES did not replace MS and the latter are
      still used in about 50% of PCI in Russia. Design of standard MS and thickness of
      struts might affect extent of neointimal proliferation which develops after stent
      implantation and eventually determines remote outcomes of IHD treatment. Thereby
      choice of optimal MS remains an actual problem. In this review we present results
      of clinical studies which compared MS with different design and thickness of
      struts.

PMID- 24888206
TI  - [Dabigatran in prevention of stroke in atrial fibrillation: three years of
      clinical application].

PMID- 24888207
TI  - [Magnesium and cardiovascular disease: new data and perspectives].
AB  - Presented data are intended to draw the attention of clinicians to question the
      importance of timely diagnosis deficiency of magnesium states and their timely
      correction of both patients by providing dietary guidelines and prescribing
      magnesium for preventive and therapy purposes.

PMID- 24888208
TI  - [Successful restoration by radiofrequency ablation and maintenance of sinus
      rhythm in a patient with longstanding (for 21 years) persistent atrial
      fibrillation].
AB  - Clinical observation of a patient with atrial fibrillation persisting throughout
      21 years is presented with discussion of results of radiofrequency catheter
      ablation.

PMID- 24888209
TI  - Examining mechanisms of change in a yoga intervention for women: the influence of
      mindfulness, psychological flexibility, and emotion regulation on PTSD symptoms.
AB  - OBJECTIVE: This study explored possible mechanisms through which symptoms of
      posttraumatic stress disorder (PTSD) were reduced in a randomized controlled
      trial comparing the effect of a yoga intervention with an assessment control.
      METHOD: We examined whether changes in psychological flexibility, mindfulness,
      and emotion regulation strategies (expressive suppression and reappraisal) were
      associated with posttreatment PTSD symptoms for 38 women with Diagnostic and
      Statistical Manual of Mental Disorders Fourth Edition full or subthreshold PTSD.
      RESULTS: Hierarchical linear regression models revealed that expressive
      suppression significantly decreased for the yoga group relative to the assessment
      control. Psychological flexibility increased significantly for the control but
      not yoga group. However, increases in psychological flexibility were associated
      with decreases in PTSD symptoms for the yoga but not control group. CONCLUSION:
      Preliminary findings suggest that yoga may reduce expressive suppression and may
      improve PTSD symptoms by increasing psychological flexibility. More research is
      needed to replicate and extend these findings.

PMID- 24888210
TI  - Resource depletion, pollen coupling, and the ecology of mast seeding.
AB  - Masting, the highly variable and synchronous production of seeds across a
      population of perennial plants, is an ecologically important, but still poorly
      understood, phenomenon. While much is known about the fitness benefits of masting
      and its effects on seed consumers and trophic interactions, less is understood
      about the proximate mechanisms of masting. The resource budget model (RBM) posits
      that masting requires more resources than plants can gain in a single year.
      Individual plants store resources until a threshold is reached and then produce
      seeds, which depletes resources so that plants cannot reproduce again for 2 or
      more years. Individuals are synchronized by pollen coupling or environmental
      forcing. We review the assumptions of these models and assess the extent to which
      they are consistent with general patterns in plant populations. We discuss the
      implications of the RBM for how plants respond to changes in the external
      environment. Overall, the RBM is a likely cause of synchrony in many, but not
      all, masting species. This mechanistic hypothesis also leads to specific, but not
      always intuitive, expectations about how plant resources affect mast seeding. 

PMID- 24888211
TI  - The effects of prolonged oral administration of the disinfectant calcium
      hypochlorite in Nigerian commercial cockerels.
AB  - This study was designed to investigate the effects of prolonged oral
      administration of calcium hypochlorite in the drinking water of commercial
      cockerels. It was carried out in order to ascertain probable toxicity associated
      with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were
      used; they were grouped into four groups of eight. Group 1, which served as the
      control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4
      received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of
      drinking water for six weeks respectively. Six weeks after the administration of
      calcium hypochlorite, blood was collected from the jugular vein to assess liver
      function, lipid profiles and for markers of oxidative stress. The results
      revealed a significant (p < 0.05) increase in alanine aminotransferase activity
      in a dose-dependent manner when compared with the control. Also, there was a
      significant (p < 0.05) increase in aspartate aminotransferase and alkaline
      phosphatase activity. Similarly, there was a significant (p < 0.05) increase in
      total cholesterol, triglycerides, high-density lipoprotein and low-density
      lipoprotein levels compared with the control. There was a significant increase in
      malondialdehyde and hydrogen peroxide generation with a concomitant significant
      (p < 0.05) decrease in serum glutathione level in a dose-dependent manner when
      compared with the control. In this study, calcium hypochloriteinduced hepatic
      damage via oxidative stress and decrease in antioxidant defense system was found.
      Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially
      harmful. 

PMID- 24888212
TI  - Compliance with referrals for non-acute child health conditions: evidence from
      the longitudinal ASENZE study in KwaZulu Natal, South Africa.
AB  - BACKGROUND: Caregiver compliance with referrals for child health services is
      essential to child health outcomes. Many studies in sub-Saharan Africa have
      examined compliance patterns for children referred for acute, life-threatening
      conditions but few for children referred for non-acute conditions. The aims of
      this analysis were to determine the rate of referral compliance and investigate
      factors associated with referral compliance in KwaZulu Natal, South Africa.
      METHODS: From September 2008-2010, a door-to-door household survey was conducted
      to identify children aged 4-6 years in outer-west eThekwini District, KwaZulu
      Natal, South Africa. Of 2,049 identified, informed consent was obtained for 1787
      (89%) children who were then invited for baseline assessments. 1581 children
      received standardized medical and developmental assessments at the study facility
      (Phase 1). Children with anemia, suspected disorders of vision, hearing, behavior
      and/or development and positive HIV testing were referred to local health
      facilities. Caregiver-reported compliance with referrals was assessed 18-24
      months later (Phase 2). Relationships between socio-demographic factors and
      referral compliance were evaluated using chi-square tests. RESULTS: Of 1581
      children, 516 received referrals for >=1 non-acute conditions. At the time of
      analysis, 68% (1078 /1581) returned for Phase 2. Analysis was limited to children
      assessed in Phase 2 who received a referral in Phase 1 (n = 303). Common referral
      reasons were suspected disorders of hearing/middle ear (22%), visual acuity (12%)
      and anemia (14%). Additionally, children testing positive for HIV (6.6%) were
      also referred. Of 303 children referred, only 45% completed referrals. Referral
      compliance was low for suspected disorders of vision, hearing and development.
      Referral compliance was significantly lower for children with younger caregivers,
      those living in households with low educational attainment and for those with
      unstable caregiving. CONCLUSIONS: Compliance with referrals for children with non
      acute conditions is low within this population and appears to be influenced by
      caregiver age, household education level and stability of caregiving. Lack of
      treatment for hearing, vision and developmental problems can contribute to long
      term cognitive difficulties. Further research is underway by this group to
      examine caregiver knowledge and attitudes about referral conditions and health
      system characteristics as potential determinants of referral compliance.

PMID- 24888213
TI  - Institutional capacity for health systems research in East and Central African
      schools of public health: experiences with a capacity assessment tool.
AB  - BACKGROUND: Despite significant investments in health systems research (HSR)
      capacity development, there is a dearth of information regarding how to assess
      HSR capacity. An alliance of schools of public health (SPHs) in East and Central
      Africa developed a tool for the self-assessment of HSR capacity with the aim of
      producing institutional capacity development plans. METHODS: Between June and
      November 2011, seven SPHs across the Democratic Republic of Congo, Ethiopia,
      Kenya, Rwanda, Tanzania, and Uganda implemented this co-created tool. The
      objectives of the institutional assessments were to assess existing capacities
      for HSR and to develop capacity development plans to address prioritized gaps. A
      mixed-method approach was employed consisting of document analysis, self
      assessment questionnaires, in-depth interviews, and institutional dialogues aimed
      at capturing individual perceptions of institutional leadership, collective HSR
      skills, knowledge translation, and faculty incentives to engage in HSR.
      Implementation strategies for the capacity assessment varied across the SPHs.
      This paper reports findings from semi-structured interviews with focal persons
      from each SPH, to reflect on the process used at each SPH to execute the
      institutional assessments as well as the perceived strengths and weaknesses of
      the assessment process. RESULTS: The assessment tool was robust enough to be
      utilized in its entirety across all seven SPHs resulting in a thorough HSR
      capacity assessment and a capacity development plan for each SPH. Successful
      implementation of the capacity assessment exercises depended on four factors: (i)
      support from senior leadership and collaborators, (ii) a common understanding of
      HSR, (iii) adequate human and financial resources for the exercise, and (iv)
      availability of data. Methods of extracting information from the results of the
      assessments, however, were tailored to the unique objectives of each SPH.
      CONCLUSIONS: This institutional HSR capacity assessment tool and the process for
      its utilization may be valuable for any SPH. The self-assessments, as well as
      interviews with external stakeholders, provided diverse sources of input and
      galvanized interest around HSR at multiple levels.

PMID- 24888214
TI  - Differences in visible light-induced pigmentation according to wavelengths: a
      clinical and histological study in comparison with UVB exposure.
AB  - The visible light spectrum is wide, and it can be hypothesized that all the
      wavelengths between 400-700 nm do not induce the same photobiological effects on
      pigmentation. We assessed the potential pro-pigmenting effects of two single
      wavelengths located at both extremities of the visible spectrum: the blue/violet
      line (lambda = 415 nm) and the red line (lambda = 630 nm). We made colorimetric,
      clinical, and histological assessments with increasing doses of those lights on
      healthy volunteers. Then, we compared these irradiations to non-exposed and UVB
      exposed skin. Colorimetric and clinical assessments showed a clear dose effect
      with the 415-nm irradiation, in both skin type III and IV subjects, whereas the
      630 nm did not induce hyperpigmentation. When compared to UVB irradiation, the
      blue-violet light induced a significantly more pronounced hyperpigmentation that
      lasted up to 3 months. Histological examination showed a significant increase of
      keratinocyte necrosis and p53 with UVB, as compared to 415- and 630-nm exposures.

PMID- 24888215
TI  - Defining an optimal stromal derived factor-1 presentation for effective
      recruitment of mesenchymal stem cells in 3D.
AB  - In "situ" tissue engineering is a promising approach in regenerative medicine,
      envisaging to potentiate the physiological tissue repair processes by recruiting
      the host's own cellular progenitors at the lesion site by means of bioactive
      materials. Despite numerous works focused the attention in characterizing novel
      chemoattractant molecules, only few studied the optimal way to present signal in
      the microenvironment, in order to recruit cells more effectively. In this work,
      we have analyzed the effects of gradients of stromal derived factor-1 (SDF-1) on
      the migratory behavior of human mesenchymal stem cells (MSCs). We have
      characterized the expression of the chemokine-associated receptor, CXCR4, using
      cytofluorimetric and real-time PCR analyses. Gradients of SDF-1 were created in
      3D collagen gels in a chemotaxis chamber. Migration parameters were evaluated
      using different chemoattractant concentrations. Our results show that cell motion
      is strongly affected by the spatio-temporal features of SDF-1 gradients. In
      particular, we demonstrated that the presence of SDF-1 not only influences cell
      motility but alters the cell state in terms of SDF-1 receptor expression and
      productions, thus modifying the way cells perceive the signal itself. Our
      observations highlight the importance of a correct stimulation of MSCs by means
      of SDF-1 in order to implement on effective cell recruitment. Our results could
      be useful for the creation of a "cell instructive material" that is capable to
      communicate with the cells and control and direct tissue regeneration.
      Biotechnol. Bioeng. 2014;111: 2303-2316. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24888216
TI  - Atrial high rate episodes in patients with dual-chamber cardiac implantable
      electronic devices: unmasking silent atrial fibrillation.
AB  - Assessment of the prevalence of silent paroxysmal atrial fibrillation (AF)
      represents a challenge, since the arrhythmia may be brief, completely
      asymptomatic, and difficult to detect. Lack of symptoms from AF should not be
      equated to lack of risk of thromboembolic complications. Today's cardiac
      implantable electronic devices (CIED) diagnostics include system diagnostics
      accurately revealing asymptomatic cardiac arrhythmias as atrial high rate
      episodes (AHRE). The presence of AHRE has been related to increased risk of
      stroke and systemic embolism. The application of anticoagulation therapy in
      patients with device-detected AHRE is yet unclear and challenging in the absence
      of randomized studies. Until further studies are available, anticoagulation
      therapy should be individualized and promoted attending to the CHADS2 score.
      Future guidelines should deal with this peculiar AF scenario to make
      professionals who routinely perform CIED follow-ups aware of these relevant
      episodes and their clinical implications. 

PMID- 24888217
TI  - Social anxiety disorder diagnostic criteria perform equally across age, comorbid
      diagnosis, and performance/interaction subtypes.
AB  - BACKGROUND: The prevalence of social anxiety disorder (SAD) is frequently higher
      in younger age groups and people with other anxiety or mood disorders; however,
      it is unclear whether these groups have a higher risk for developing SAD or are
      simply more likely to endorse diagnostic criteria than other people with similar
      levels of social anxiety. Explicitly testing the assumption all people respond to
      structured diagnostic interviews in comparable ways (measurement invariance) is
      essential in ensuring systematic response biases do not create spurious group
      differences. This research aims to systematically test whether age, comorbidity
      status, or types of social fears affect responses to a structured diagnostic
      interview. DESIGN AND METHODS: Responses from 1755 participants in a large-scale
      survey of mental health in Australia screening into the social phobia/SAD section
      of the Composite International Diagnostic Interview were used. Three series of
      multigroup confirmatory factor analyses for categorical data systematically
      tested for increasingly strict levels of measurement invariance. RESULTS:
      Overall, patterns of responding to diagnostic criteria were comparable across the
      groups, supporting assumptions of measurement invariance. CONCLUSIONS:
      Establishment of invariance supports the interpretation of differences between
      age, comorbidity status, and types of social situations feared as genuine
      differences in experience as opposed to measurement biases.

PMID- 24888218
TI  - Synthesis of soft colloids with well-controlled softness.
AB  - We report a novel method to prepare soft colloids with well-controlled softness.
      The softness of the colloids was characterised by atomic force microscopy and
      rheometry. Possible applications of such soft colloids in uniform particle
      coatings are demonstrated. 

PMID- 24888219
TI  - Abstracts of the 34th Annual Meeting of the American Society for Reproductive
      Immunology, 2-5 june, 2014, Long Beach, New York.

PMID- 24888221
TI  - No difference between standard and high flexion cruciate retaining total knee
      arthroplasty: a prospective randomised controlled study.
AB  - PURPOSE: The purpose of this prospective, randomised, double-blind study was to
      test the hypotheses that patients with high-flexion total knee arthroplasty (TKA)
      have (1) a wider/greater range of motion (ROM) post-operatively and (2) higher
      levels of knee society score (KSS) and WOMAC score post-operatively compared to
      standard TKA. METHODS: In this study, 28 high flexion with 31 standard TKAs were
      compared. We measured ROM, pre-operatively, on day 3, 7, 28, and after 6 and 36
      months post-operatively as well as KSS and WOMAC score pre-operatively, on day 28
      and after 6 and 36 months post-operatively. RESULTS: No statistically significant
      differences were found between both groups with regard to the target parameters.
      The mean ROM was 113 degrees  (range 80 degrees -140 degrees , SD 13.4 degrees )
      in the control group (standard TKA) and 117 degrees  (range 90 degrees -140
      degrees , SD 12.3) in the study group (high-flexion TKA) at 36 months follow-up
      [p = not significant (n.s.)]. The KSS pre-operatively was 38.2 (range 8-64, SD
      15.8) in the control group and 45.9 (range 8-74, SD 16.0) in the study group
      (n.s.) increasing to 157.6 in the control group and 156.7 in the study group (p =
      n.s) at 36 months follow-up. CONCLUSION: This study could not confirm significant
      benefits of high-flexion TKA compared to standard TKA with regard to ROM and
      higher levels of KSS and WOMAC score. LEVEL OF EVIDENCE: I.

PMID- 24888222
TI  - Measurement of tibial tuberosity-trochlear groove distance: evaluation of inter-
      and intraobserver correlation dependent on the severity of trochlear dysplasia.
AB  - PURPOSE: Excessive tibial tuberosity-trochlear groove distance (TT-TG) is
      considered as one of the major risk factors in patellofemoral instability (PFI).
      TT-TG characterises the lateralisation of the tibial tuberosity and the
      medialisation of the trochlear groove in the case of trochlear dysplasia. The aim
      of this study was to assess the inter- and intraobserver reliability of the
      measurement of TT-TG dependent on the grade of trochlear dysplasia. METHODS:
      Magnetic resonance imaging (MRI) scans of 99 consecutive knee joints were
      analysed retrospectively. Hereof, 61 knee joints presented with a history of PFI
      and 38 had no symptoms of PFI. After synopsis of the axial MRI scans with true
      lateral radiographs of the knee, the 61 knees presenting with PFI were assessed
      in terms of trochlear dysplasia. The knees were distributed according to the four
      type classification system described by Dejour. RESULTS: Regarding interobserver
      correlation for the measurements of TT-TG in trochlear dysplasia, we found r=0.89
      (type A), r=0.90 (type B), r=0.74 (type C) and 0.62 (type D) for Pearson's
      correlation coefficient. Regarding intraobserver correlation, we calculated
      r=0.89 (type A), r=0.91 (type B), r=0.77 (type C) and r=0.71 (type D),
      respectively. Pearson's correlation coefficient for the measurement of TT-TG in
      normal knees resulted in r=0.87 for interobserver correlation and r=0.90 for
      intraobserver correlation. CONCLUSION: Decreasing inter- and intraobserver
      correlation for the measurement of TT-TG with increasing severity of trochlear
      dysplasia was detected. In our opinion, the measurement of TT-TG is of
      significance in low-grade trochlear dysplasia. The final decision to perform a
      distal realignment procedure based on a pathological TT-TG in the presence of
      high-grade trochlear dysplasia should be reassessed properly. LEVEL OF EVIDENCE:
      Retrospective study, Level II.

PMID- 24888224
TI  - Repair of a complete radial tear in the midbody of the medial meniscus using a
      novel crisscross suture transtibial tunnel surgical technique: a case report.
AB  - Complete radial meniscus tears have been reported to result in deleterious
      effects in the knee joint if left unrepaired. An emphasis on meniscal
      preservation is important in order to restore native meniscal function. In this
      case report, a complete radial tear of the medial meniscus midbody was repaired
      using a novel crisscross suture transtibial technique. This technique secured the
      anterior and posterior meniscal horns, which were released from their extruded
      and scarred position along the capsule, using crisscrossing sutures passed
      through two transtibial tunnels and secured over a bone bridge on the
      anterolateral tibia. In addition, the repair was supplemented with the injection
      of platelet-rich plasma and bone marrow aspirate concentrate to promote the
      healing of the meniscal tissue. Complete healing on second-look arthroscopy is
      presented, including in the previously unreported white-white meniscal zone.

PMID- 24888225
TI  - Z-plasty lengthening of the flexor digitorum profundus at the wrist (zone 5) for
      the treatment of jersey finger: anatomical study and evaluation of advancement
      obtained.
AB  - AIM: The aim of this study was to conduct an anatomical evaluation of advancement
      obtained from Z-plasty lengthening of the flexor digitorum profundus at the wrist
      (zone 5) for the treatment of jersey finger. INTRODUCTION: The avulsion of the
      flexor digitorum profundus from its distal insertion, or jersey finger, is an
      injury commonly missed in the accident and emergency department. Typically, after
      3 weeks, the retracted tendon stump prevents direct reinsertion of the tendon.
      Sawaya et al. have proposed a treatment involving a zone 5 Z-plasty lengthening
      on the fourth finger. We conducted an anatomical study to evaluate the tendon
      advancement that could be obtained in the long digits using this method. METHOD:
      Tendon avulsion was recreated in 17 fresh cadaver hands by severing the flexor
      digitorum profundus from its distal insertion. A 3-, 4- or 5-cm Z-plasty was
      performed at the wrist and, after section of the vinculum breve, the advancement
      was measured with wrist extension at 0 degrees . RESULTS: A total of 68 tendon
      reconstructions were performed. The mean advancement obtained was 1.5 cm (max:
      2.5 cm; min: 0.5 cm), 2.3 cm (max: 3.2 cm; min: 1.3 cm) and 2.5 cm (max: 3.5 cm;
      min: 1.7 cm) for 3-, 4- and 5-cm Z-plasties, respectively. Tendon advancement in
      the ring finger and middle finger was limited by the lumbrical (2 cases) or by
      synovial adhesions in the carpal tunnel (16 cases). There was no such limitation
      for the index finger. DISCUSSION: Advancement of the flexor digitorum profundus
      by a 4-cm Z-plasty at the wrist seems to be a useful technique for reinsertion of
      a retracted tendon. The best results were obtained in the index finger. This
      technique could be considered as an alternative to palliative surgery or a tendon
      graft. In the other fingers, the fact that advancement was limited due to
      Verdan's quadriga effect and synovial adhesions highlights the significance of
      the relationship between the tendons themselves and with their environment on the
      physiology of finger flexion.

PMID- 24888226
TI  - Updated scar management practical guidelines: non-invasive and invasive measures.
AB  - Hypertrophic scars and keloids can be aesthetically displeasing and lead to
      severe psychosocial impairment. Many invasive and non-invasive options are
      available for the plastic (and any other) surgeon both to prevent and to treat
      abnormal scar formation. Recently, an updated set of practical evidence-based
      guidelines for the management of hypertrophic scars and keloids was developed by
      an international group of 24 experts from a wide range of specialities. An
      initial set of strategies to minimize the risk of scar formation is applicable to
      all types of scars and is indicated before, during and immediately after surgery.
      In addition to optimal surgical management, this includes measures to reduce skin
      tension, and to provide taping, hydration and ultraviolet (UV) protection of the
      early scar tissue. Silicone sheeting or gel is universally considered as the
      first-line prophylactic and treatment option for hypertrophic scars and keloids.
      The efficacy and safety of this gold-standard, non-invasive therapy has been
      demonstrated in many clinical studies. Other (more specialized) scar treatment
      options are available for high-risk patients and/or scars. Pressure garments may
      be indicated for more widespread scarring, especially after burns. At a later
      stage, more invasive or surgical procedures may be necessary for the correction
      of permanent unaesthetic scars and can be combined with adjuvant measures to
      achieve optimal outcomes. The choice of scar management measures for a particular
      patient should be based on the newly updated evidence-based recommendations
      taking individual patient and wound characteristics into consideration. 

PMID- 24888223
TI  - Rotational alignment of the distal femur: anthropometric measurements with CT
      based patient-specific instruments planning show high variability of the
      posterior condylar angle.
AB  - PURPOSE: Finding the anatomical landmarks used for correct femoral axial
      alignment can be difficult. The posterior condylar line (PCL) is probably the
      easiest to find during surgery. The aim of this study was to analyse whether a
      predetermined fixed angle referencing of the PCL could help find the surgical
      epicondylar axis (SEA) and this based on a large CT database with enough
      Caucasian diversity to be representable. METHODS: A total of 2,637 CT scans and
      3D reconstructions from patients on four continents, executed for preoperative
      planning and creation of patient-specific instrumentation, were used to perform
      anthropometric measurements and to measure the posterior condylar angle (PCA)
      between the surgical epicondylar angle and the PCL. RESULTS: The mean (SD) PCA
      was 4 degrees  (1.4 degrees ) of external rotation. A significant correlation was
      found between more external rotation of the SEA and more proximal varus of the
      tibia or more distal valgus of the femur. For 59% of the study population, 4
      degrees  external rotation from the PCL would be the right amount of axial
      rotation to align the femoral component in line with the SEA. Nine per cent needs
      less, and 32% needs more than 4 degrees  of axial rotation. On 105 (4%) CT-based
      3D models, external rotation between 7 degrees  and 11 degrees  was measured and
      77 (73%) of those cases were in varus or neutral alignment. In 132 patients,
      bilateral measurements were available and 94 (71%) had rotation within 1 degrees 
      of the opposite side. This last finding underlines that there is even an intra
      individual difference in distal femoral anatomy that can range from 1 degrees  to
      5 degrees . CONCLUSIONS: This study was performed on a very large anthropometric
      CT and 3D models database and showed that there is a 41% risk of malalignment if
      a fixed PCA referenced of the PCL is used in total knee arthroplasty. The
      clinical importance of this study is the observation that femoral axial anatomy
      is individual and also that it is determined by the tibial anatomy. A group of
      patients needs more than the average external rotation because they have more
      distal femoral valgus with dysplastic condyles or more proximal tibial varus with
      a bigger medial condyle. LEVEL OF EVIDENCE: III.

PMID- 24888227
TI  - The impact of a single surgical intervention for patients with a cleft lip living
      in rural Ethiopia.
AB  - BACKGROUND: Humanitarian organisations commonly provide reconstructive treatment
      for patients with cleft lip within developing countries, but follow-up is often
      non-existent, particularly for those living in rural areas. This study aimed to
      assess whether a single surgical intervention was sufficient to produce an
      observable change to the life of a patient with cleft lip living in rural
      Hararghe in eastern Ethiopia. METHODS: 356 patients with isolated cleft lips, who
      received a single surgical treatment at least 6 months previously, were evaluated
      in 21 rural health centres. RESULTS: Patients and their families expressed
      unhappiness before treatment, mainly because the society reacted negatively
      towards the deformities, isolating the patients from community activities.
      Postoperatively, the percentage of school-aged children participating in
      education increased from 46% to 79%, some older patients were able to marry, but
      employment was unaffected. The prevalence of wound dehiscence in the lip repair
      was 3% and occurred more frequently in patients with a bilateral cleft lip
      compared to a unilateral cleft lip (p < 0.001, RR 49.25, 95% CI 6.7-1037.35).
      CONCLUSIONS: We demonstrated that follow-up can be achieved by charitable
      organisations treating rural patients and that the majority of patients report a
      positive impact following surgical intervention. We recommend that bilateral
      cleft lips have a more intense rural aftercare.

PMID- 24888228
TI  - Notch1 signaling controls cell proliferation, apoptosis and differentiation in
      lung carcinoma.
AB  - OBJECTIVES: The role of Notch signaling in human lung cancer still remains
      unclear, and there has been and stills a debate, on the extent to which Notch
      ligands and receptors are involved in lung cancer development. This study was
      carried out to investigate the role of Notch1 signaling in the proliferation and
      differentiation of human lung cancer cells. METHODS: We used small interfering
      RNA (siRNA) technology to down-regulate the expression of Notch1 in small cell
      lung carcinoma (SCLC) cells; H69AR and SBC-3, as well as in non-small cell lung
      carcinoma (NSCLC) cells; A549 adenocarcinoma (ADC) and H2170 squamous cell
      carcinoma (SCC). Also, we transfected venus Notch1 intracellular domain (v.NICD)
      plasmid into the human SCLC line H69 and H1688. In addition, H1688 cells with
      activated Notch1 were injected into immune-compromised Rag2(-/-) Jak3(-/-) mice
      for analysis of ex vivo tumor growth and differentiation phenotype. RESULTS:
      Notch1 controls cell proliferation and apoptosis in both SCLC and A549; but not
      in H2170 cell line. Overexpression of Notch1 in SCLC markedly decreased cell
      proliferation via apoptosis. The subcutaneous tumors arising from xenotransplaned
      SCLC cells transfected with Notch1 showed "epithelial-like glandular"
      arrangement, with positive Alcian blue staining and reduction in neuroendocrine
      markers. CONCLUSION: Notch1 up regulation has an inhibitory effect on cell growth
      and NE differentiation in SCLC, with induction of an epithelial-like morphology
      of cells in tissue samples. In NSCLC, Notch1 expression has a tumor inhibitory
      effect on ADC cells, but not SCC cells.

PMID- 24888229
TI  - BRAF V600E-mutated lung adenocarcinoma with metastases to the brain responding to
      treatment with vemurafenib.
AB  - Somatic BRAF mutations have been reported in 1-4% of non-small cell lung cancer
      (NSCLC), primarily in adenocarcinomas with the BRAF (V600E) mutation in about 50%
      of the cases. The role of BRAF mutation in NSCLC and the treatment for tumors
      with such mutations is still evolving. Our patient had metastatic NSCLC with
      metastases to her brain. Due to the BRAF (V600E) mutation in her tumor and her
      poor functional status, we offered her off-label treatment with vemurafenib, a
      BRAF inhibitor approved for use in metastatic melanoma. Our patient's visceral
      disease improved supporting vemurafenib's efficacy in the treatment of metastatic
      BRAF-mutated NSCLC. The regression of intracranial disease indicated vemurafenib
      was able to cross the blood-brain barrier and was efficacious in treating brain
      metastases in this patient with lung cancer. 

PMID- 24888230
TI  - DISRUPT: a randomised phase 2 trial of ombrabulin (AVE8062) plus a taxane
      platinum regimen as first-line therapy for metastatic non-small cell lung cancer.
AB  - BACKGROUND: DISRUPT evaluated whether adding the vascular-disrupting agent
      ombrabulin to a taxane-platinum doublet in the first-line setting improved
      progression-free survival (PFS) in patients with metastatic non-small cell lung
      cancer (NSCLC). METHODS: Patients were randomised to ombrabulin 35 mg/m(2) or
      placebo followed by a taxane-platinum regimen every 3 weeks. RESULTS: Overall,
      176 patients were randomised. After 124 events, median PFS was not significantly
      improved with ombrabulin vs placebo (5.65 vs 5.45 months; HR 0.948; 60% CI 0.813
      1.106; one-sided P=0.39). The two groups showed similar overall survival (median
      11.0 months in both groups), objective response rate (32% ombrabulin; 31%
      placebo) and safety profiles. CONCLUSION: This study did not meet its primary
      endpoint of improving PFS by adding ombrabulin to a taxane-platinum regimen for
      first-line treatment of metastatic NSCLC.

PMID- 24888231
TI  - Viable Legionella pneumophila bacteria in natural soil and rainwater puddles.
AB  - AIMS: For the majority of sporadic Legionnaires' disease cases the source of
      infection remains unknown. Infection may possible result from exposure to
      Legionella bacteria in sources that are not yet considered in outbreak
      investigations. Therefore, potential sources of pathogenic Legionella bacteria-
      natural soil and rainwater puddles on roads--were studied in 2012. METHODS AND
      RESULTS: Legionella bacteria were detected in 30% (6/20) of soils and 3.9% (3/77)
      of rainwater puddles by amoebal coculture. Legionella pneumophila was isolated
      from two out of six Legionella positive soil samples and two out of three
      Legionella positive rainwater samples. Several other species were found including
      the pathogenic Leg. gormanii and Leg. longbeachae. Sequence types (ST) could be
      assigned to two Leg. pneumophila strains isolated from soil, ST710 and ST477, and
      one strain isolated from rainwater, ST1064. These sequence types were previously
      associated with Legionnaires' disease patients. CONCLUSIONS: Rainwater and soil
      may be alternative sources for Legionella. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The detection of clinically relevant strains indicates that rainwater and soil
      are potential sources of Legionella bacteria and future research should assess
      the public health implication of the presence of Leg. pneumophila in rainwater
      puddles and natural soil.

PMID- 24888233
TI  - Print-based self-help interventions for smoking cessation.
AB  - BACKGROUND: Many smokers give up smoking on their own, but materials giving
      advice and information may help them and increase the number who quit
      successfully. OBJECTIVES: The aims of this review were to determine: the
      effectiveness of different forms of print-based self-help materials, compared
      with no treatment and with other minimal contact strategies; the effectiveness of
      adjuncts to print-based self help, such as computer-generated feedback, telephone
      hotlines and pharmacotherapy; and the effectiveness of approaches tailored to the
      individual compared with non-tailored materials. SEARCH METHODS: We searched the
      Cochrane Tobacco Addiction Group trials register. Date of the most recent search
      April 2014. SELECTION CRITERIA: We included randomized trials of smoking
      cessation with follow-up of at least six months, where at least one arm tested a
      print-based self-help intervention. We defined self help as structured
      programming for smokers trying to quit without intensive contact with a
      therapist. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the
      participants, the nature of the self-help materials, the amount of face-to-face
      contact given to intervention and to control conditions, outcome measures, method
      of randomization, and completeness of follow-up.The main outcome measure was
      abstinence from smoking after at least six months follow-up in people smoking at
      baseline. We used the most rigorous definition of abstinence in each trial, and
      biochemically validated rates when available. Where appropriate, we performed
      meta-analysis using a fixed-effect model. MAIN RESULTS: We identified 74 trials
      which met the inclusion criteria. Many study reports did not include sufficient
      detail to judge risk of bias for some domains. Twenty-eight studies (38%) were
      judged at high risk of bias for one or more domains but the overall risk of bias
      across all included studies was judged to be moderate, and unlikely to alter the
      conclusions.Thirty-four trials evaluated the effect of standard, non-tailored
      self-help materials. Pooling 11 of these trials in which there was no face-to
      face contact and provision of structured self-help materials was compared to no
      intervention gave an estimate of benefit that just reached statistical
      significance (n = 13,241, risk ratio [RR] 1.19, 95% confidence interval [CI] 1.04
      to 1.37). This analysis excluded two trials with strongly positive outcomes that
      introduced significant heterogeneity. Six further trials without face-to-face
      contact in which the control group received alternative written materials did not
      show evidence for an effect of the smoking self-help materials (n = 7023, RR
      0.88, 95% CI 0.74 to 1.04). When these two subgroups were pooled, there was no
      longer evidence for a benefit of standard structured materials (n = 20,264, RR
      1.06, 95% CI 0.95 to 1.18). We failed to find evidence of benefit from providing
      standard self-help materials when there was brief contact with all participants
      (5 trials, n = 3866, RR 1.17, 95% CI 0.96 to 1.42), or face-to-face advice for
      all participants (11 trials, n = 5365, RR 0.97, 95% CI 0.80 to 1.18).Thirty-one
      trials offered materials tailored for the characteristics of individual smokers,
      with controls receiving either no materials, or stage matched or non-tailored
      materials. Most of the trials used more than one mailing. Pooling these showed a
      benefit of tailored materials (n = 40,890, RR 1.28, 95% CI 1.18 to 1.37) with
      moderate heterogeneity (I2 = 32%). The evidence is strongest for the subgroup of
      nine trials in which tailored materials were compared to no intervention (n =
      13,437, RR 1.35, 95% CI 1.19 to 1.53), but also supports tailored materials as
      more helpful than standard materials. Part of this effect could be due to the
      additional contact or assessment required to obtain individual data, since the
      subgroup of 10 trials where the number of contacts was matched did not detect an
      effect (n = 11,024, RR 1.06, 95% CI 0.94 to 1.20). In two trials including a
      direct comparison between tailored materials and brief advice from a health care
      provider, there was no evidence of a difference, but confidence intervals were
      wide (n = 2992, RR 1.13, 95% CI 0.86 to 1.49).Only four studies evaluated self
      help materials as an adjunct to nicotine replacement therapy, with no evidence of
      additional benefit (n = 2291, RR 1.05, 95% CI 0.88 to 1.25). A small number of
      other trials failed to detect benefits from using additional materials or
      targeted materials, or to find differences between different self-help
      programmes. AUTHORS' CONCLUSIONS: Standard, print-based self-help materials
      increase quit rates compared to no intervention, but the effect is likely to be
      small. We did not find evidence that they have an additional benefit when used
      alongside other interventions such as advice from a healthcare professional, or
      nicotine replacement therapy. There is evidence that materials that are tailored
      for individual smokers are more effective than non-tailored materials, although
      the absolute size of effect is still small. Available evidence tested self-help
      interventions in high income countries; further research is needed to investigate
      their effect in contexts where more intensive support is not available.

PMID- 24888232
TI  - Enhanced bone healing by improved fibrin-clot formation via fibrinogen adsorption
      on biphasic calcium phosphate granules.
AB  - OBJECTIVES: Fibrin clots play an important role in bone tissue regeneration. This
      study aimed at improving the fibrin-clotting rate by coating the surface of
      biphasic calcium phosphate (BCP) granules with fibrinogen (FNG). METHODS AND
      MATERIALS: FNG was coated on the BCP surface using an adsorption and freeze
      drying method. The surface morphology of FNG-adsorbed BCP (FNG-BCP) was
      characterized using scanning electron microscopy (SEM), and the stability of the
      adsorbed FNG evaluated by gel electrophoresis and circular dichroism (CD)
      analysis. The biocompatibility of FNG-BCP was evaluated in vitro using human
      mesenchymal stem cells, and in vivo bone-healing efficiency determined using a
      rabbit calvarial bone defect model. RESULTS: SEM studies showed numerous
      irregularly distributed FNG fractions adsorbed onto the surface of BCP granules.
      Gel electrophoresis, CD analysis, and in vitro coagulation results showed that
      the adsorbed FGN maintained its native protein structure and clotting properties.
      Biocompatibility experiments showed that cell proliferation and adhesion were
      improved in cells cultivated on the FNG-BCP granules. After surgical implantation
      into the bone defects, the FNG-BCP granules coagulated at the defect site by
      reacting with the blood discharged from the surgical site tissue. In addition, at
      8 weeks, the volume of FNG40-BCP (P = 0.012) was significantly higher than that
      of BCP alone in the newly formed bone. CONCLUSIONS: These results indicate that
      self-coagulating FNG-CBP granules may have the potential to be used as a bone
      substitute for enabling effective bone repair through rapid fibrin-clot
      formation.

PMID- 24888234
TI  - Induction of ram bone marrow mesenchymal stem cells into germ cell lineage using
      transforming growth factor-beta superfamily growth factors.
AB  - Several studies have proposed that in vitro generation of germ cells (GCs) from
      stem cells can be considered a future option for infertility treatment.
      Mesenchymal stem cells (MSCs) have the capability to differentiate into male GCs
      with the use of inducers such as retinoic acid. Transforming growth factor-beta 1
      (TGFb1) has been shown to play important roles in male fertility and
      spermatogenesis. Bone morphogenic protein 4 (BMP4) and BMP8b are also involved in
      the derivation of primordial GCs (PGCs) from epiblast cells. Therefore, this
      study aims to determine whether TGFb1, BMP4 and BMP8b can initiate
      transdifferentiation of MSCs into GCs in vitro and to determine the type of
      changes that occur in the expression of GC-specific markers. In this study, we
      have divided passage-3 ram bone marrow (BM)-MSCs into three main groups (BMP4,
      BMP8b and TGFb1) which were separately treated with 10 ng/ml TGFb1, 100 ng/ml
      BMP4 and 100 ng/ml BMP8b for a period of 21 days. We have evaluated the ability
      of these groups to differentiate into GCs by assessing expressions of GC-specific
      markers with reverse transcription PCR (RT-PCR), quantitative RT-PCR (qRT-PCR),
      immunocytochemistry, morphological changes and alkaline phosphatase (ALP)
      activity. Our results showed that BMP4 and BMP8b induced PGCs properties in some
      BM-MSCs and TGFb1 formed spermatogonial stem cells (SSCs) and spermatogonia-like
      cells in BM-MSCs culture. The important results of this study provide the basis
      for additional studies to determine the exact mechanism of GCs differentiation
      and possibly solve the problem of infertility.

PMID- 24888235
TI  - Regional analysis of striatal and cortical amyloid deposition in patients with
      Alzheimer's disease.
AB  - We aimed to analyse the detailed distribution pattern of amyloid-beta (Abeta) in
      the striatum, and to examine whether there is any correlation between Abeta
      deposition levels in the striatum and cortical regions. Twenty patients with
      Alzheimer's disease underwent positron emission tomography using (11) C
      Pittsburgh Compound B ((11) C-PiB) to quantify the Abeta deposition. Volumes-of
      interest analyses were performed on the ventral striatum (VST), pre-commissural
      dorsal caudate (pre-DCA), post-commissural caudate (post-CA), pre-commissural
      dorsal putamen (pre-DPU), and post-commissural putamen (post-PU), followed by
      exploratory voxel-wise analyses. Volumes-of-interest analyses of (11) C-PiB
      binding showed: VST > pre-DPU (P = 0.004), VST > pre-DCA (P < 0.0001), pre-DPU >
      post-PU (P < 0.0001), and pre-DCA > post-CA (P < 0.0001), consistent with visual
      inspection of the (11) C-PiB images. Exploratory voxel-wise analyses of (11) C
      PiB binding showed a positive correlation between the VST and the medial part of
      the orbitofrontal area (P < 0.01 family-wise error corrected). This study
      confirmed that there were ventral > dorsal, and anterior > posterior gradients of
      Abeta deposition in patients with Alzheimer's disease, and provided the first
      evidence of a robust correlation between Abeta deposition levels in the VST and
      the medial part of the orbitofrontal area. There are well-known anatomical and
      functional links between these areas. These findings indicated that brain Abeta
      deposition was not randomly distributed, but had characteristic patterns related
      to anatomical connectivity and/or functional networks. 

PMID- 24888236
TI  - Asymmetric palladium-catalyzed allylic alkylation using dialkylzinc reagents: a
      remarkable ligand effect.
AB  - A serendipitously discovered palladium-catalyzed asymmetric allylic alkylation
      reaction with diorganozinc reagents, which displays broad functional group
      compatibility, is reported. This novel transformation hinges on a remarkable
      ligand effect which overrides the standard "umpolung" reactivity of allyl
      palladium intermediates in the presence of dialkylzincs. Owing to its mild
      conditions, enantioselective allylic alkylations of racemic allylic electrophiles
      are possible in the presence of sensitive functional groups. 

PMID- 24888237
TI  - Screening for latent tuberculosis infection in low-incidence areas.

PMID- 24888238
TI  - Programmed cell death 4 and microRNA 21 inverse expression is maintained in cells
      and exosomes from ovarian serous carcinoma effusions.
AB  - BACKGROUND: Ovarian serous carcinoma (OSC) is a fatal gynecologic malignancy
      usually presenting with bilateral localization and malignant peritoneal effusion.
      Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is
      directly controlled by microRNA-21 (miR-21). Exosomes are small cell-derived
      vesicles that participate in intercellular communication, delivering their cargo
      of molecules to specific cells. Exosomes are involved in several physiological
      and pathological processes including oncogenesis, immunomodulation, angiogenesis,
      and metastasis. The current study analyzed the expression of PDCD4 and miR-21 in
      resected OSC specimens and in cells and exosomes from OSC peritoneal effusions.
      METHODS: PDCD4 was immunohistochemically examined in 14 normal ovaries, 14 serous
      cystadenoma (CA), and 14 OSC cases. Quantitative reverse transcriptase-polymerase
      chain reaction analysis of PDCD4 and miR-21 expression was performed in CA and
      OSC cases and in cells and exosomes obtained from 10 OSC and 10 nonneoplastic
      peritoneal effusions. miR-21 was also evaluated by in situ hybridization.
      RESULTS: Immunohistochemistry demonstrated a gradual PDCD4 loss from normal
      ovaries to CA and OSC specimens. Quantitative reverse transcriptase-polymerase
      chain reaction displayed higher PDCD4 messenger RNA levels in CA specimens
      compared with OSC cases and highlighted miR-21 overexpression in OSC specimens.
      In situ hybridization detected miR-21 only in OSC cells. This PDCD4 and miR-21
      inverse expression was also noted in cells and exosomes from OSC peritoneal
      effusions compared with nonneoplastic effusions. CONCLUSIONS: PDCD4 and miR-21
      are involved in OSC oncogenesis. The transfer of miR-21 by exosomes could promote
      oncogenic transformation in target cells distant from the primary tumor without
      direct colonization by cancer cells and could be used as a diagnostic tool.

PMID- 24888239
TI  - Vascular endothelial growth factor mRNA levels as a biomarker for short-term N
      butyl-N-(4-hydroxybutyl) nitrosamine-induced rat bladder carcinogenesis bioassay.
AB  - Generically, carcinogenic effects of chemicals in bladder carcinogenesis are
      judged by induction of papillary or nodular (PN) hyperplasia in rats given N
      butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 4 weeks and the test chemical for
      22-28 weeks. However, upregulation of vascular endothelial growth factor (VEGF)
      begins early in rat BBN bladder carcinogenesis. To establish a short-term rat
      bladder carcinogenic bioassay, we analyzed the correlations between VEGF, VEGF
      mRNA and bladder lesions inductions at 10 and 26 weeks after BBN treatment. Six
      week-old male Wistar (slc) rats were given 0.05% BBN for 4, 10 or 26 weeks. To
      avoid individual rat bias, the bladders were investigated by partial cystectomy
      at 10 weeks and total cystectomy at 26 weeks. After induction, PN hyperplasia and
      carcinoma in rats increased with the length of BBN treatment and
      immunohistochemical VEGF expression also increased following carcinogenesis, but
      the immunoreactivity of individual lesions was quite variable. Moreover,
      induction of PN hyperplasia at 10 weeks' BBN treatment was not significantly
      correlated with that at 26 weeks' treatment; thus, it was not possible to predict
      the carcinogenic effect due to the induction of PN hyperplasia at 26 weeks' BBN
      treatment by that at 10 weeks' treatment. However, VEGF mRNA levels of rat
      bladders at 10 weeks' BBN treatment revealed a strong significant correlation
      with the incidence of bladder lesions at 26 weeks' treatment. Here, we suggest
      that quantitative VEGF mRNA levels are a good biomarker for a short-term BBN
      induced bioassay for rat bladder carcinogenesis.

PMID- 24888241
TI  - The beauty of age and digital publishing.

PMID- 24888240
TI  - The explosive radiation of Cheirolophus (Asteraceae, Cardueae) in Macaronesia.
AB  - BACKGROUND: Considered a biodiversity hotspot, the Canary Islands have been the
      key subjects of numerous evolutionary studies concerning a large variety of
      organisms. The genus Cheirolophus (Asteraceae) represents one of the largest
      plant radiations in the Canarian archipelago. In contrast, only a few species
      occur in the Mediterranean region, the putative ancestral area of the genus.
      Here, our main aim was to reconstruct the phylogenetic and biogeographic history
      of Cheirolophus with special focus on explaining the origin of the large Canarian
      radiation. RESULTS: We found significant incongruence in phylogenetic
      relationships between nuclear and plastid markers. Each dataset provided
      resolution at different levels in Cheirolophus: the nuclear markers resolved the
      backbone of the phylogeny while the plastid data provided better resolution
      within the Canarian clade. The origin of Cheirolophus was dated in the Mid-Late
      Miocene, followed by rapid diversification into the three main Mediterranean
      lineages and the Macaronesian clade. A decrease in diversification rates was
      inferred at the end of the Miocene, with a new increase in the Late Pliocene
      concurrent with the onset of the Mediterranean climate. Diversification within
      the Macaronesian clade started in the Early-Mid Pleistocene, with unusually high
      speciation rates giving rise to the extant insular diversity. CONCLUSIONS:
      Climate-driven diversification likely explains the early evolutionary history of
      Cheirolophus in the Mediterranean region. It appears that the exceptionally high
      diversification rate in the Canarian clade was mainly driven by allopatric
      speciation (including intra- and interisland diversification). Several intrinsic
      (e.g. breeding system, polyploid origin, seed dispersal syndrome) and extrinsic
      (e.g. fragmented landscape, isolated habitats, climatic and geological changes)
      factors probably contributed to the progressive differentiation of populations
      resulting in numerous microendemisms. Finally, hybridization events and emerging
      ecological adaptation may have also reinforced the diversification process.

PMID- 24888242
TI  - Development and validation of the tool to assess inpatient satisfaction with care
      from hospitalists.
AB  - OBJECTIVES: To develop and validate a new inpatient satisfaction metric to assess
      patients' perceptions of hospitalist performance. PATIENTS AND METHODS: We
      developed the Tool to Assess Inpatient Satisfaction with Care from Hospitalists
      (TAISCH) by building upon the theoretical underpinnings of the quality of care
      measures that the Society of Hospital Medicine endorses. TAISCH was completed by
      inpatients at an academic institution between September 2012 and December 2012
      after they had been cared for by the same hospitalist provider for at least 2
      consecutive days. Content, internal structure, and convergent/discriminant
      validity evidence were assessed for TAISCH. RESULTS: A total of 203 patients each
      rated 1 of our 29 hospitalists (patient response rate: 88%). Factor analyses
      resulted in a single factor with 15 items. Reliability of TAISCH was good
      (Cronbach's alpha = .88). The hospitalists' average TAISCH score ranged from 3.25
      to 4.28 (mean [standard deviation] = 3.82 [0.24]; possible score range: 1-5). The
      relationship between TAISCH with a validated empathy scale and a global provider
      satisfaction question revealed significant positive associations (beta = 12.2,
      and beta = 11.2 respectively, both P < 0.001). At the provider level, no
      significant correlation was noted between the Press Ganey Physician score and
      TAISCH (r = 0.91, P = 0.51). CONCLUSION: TAISCH collects patient satisfaction
      data that are attributable to specific hospitalist providers. The timeliness of
      the TAISCH data collection also makes real-time service recovery possible, which
      is unachievable with other commonly used patient satisfaction metrics.

PMID- 24888243
TI  - Concurrent stabilization of pi-donor and pi-acceptor ligands in aromatized and
      dearomatized pincer [(PNN)Re(CO)(O)2] complexes.
AB  - Aromatized cationic [(PNN)Re(pi acid)(O)2](+) (1) and dearomatized neutral
      [(PNN*)Re(pi acid)(O)2] (2) complexes (where pi acid=CO (a), tBuNC (b), or (2,6
      Me2)PhNC (c)), possessing both pi-donor and pi-acceptor ligands, have been
      synthesized and fully characterized. Reaction of [(PNN)Re(O)2](+) (4) with
      lithiumhexamethyldisilazide (LiHMDS) yield the dearomatized [(PNN*)Re(O)2] (3).
      Complexes 1 and 2 are prepared from the reaction of 4 and 3, respectively, with
      CO or isocyanides. Single-crystal X-ray structures of 1 a and 1 b show the
      expected trans-dioxo structure, in which the oxo ligands occupy the axial
      positions and the pi-acidic ligand occupies the equatorial plane in an overall
      octahedral geometry about the rhenium(V) center. DFT studies revealed the
      stability of complexes 1 and 2 arises from a pi-backbonding interaction between
      the d(xy) orbital of rhenium, the pi orbital of the oxo ligands, and the pi*
      orbital of CO/isocyanide.

PMID- 24888247
TI  - 4217C>A polymorphism in carbamoyl-phosphate synthase 1 gene may not associate
      with hyperammonemia development during valproic acid-based therapy.
AB  - Valproic acid, which is widely used to treat various types of epilepsy, may cause
      severe hyperammonemia. However, the mechanism responsible for this side effect is
      not readily apparent. Polymorphisms in the genes encoding carbamoyl-phosphate
      synthase 1 (CPS1) and N-acetylglutamate synthase (NAGS) were recently reported to
      be risk factors for the development of hyperammonemia during valproic acid-based
      therapy. This study aimed to examine the influence of patient characteristics,
      including polymorphisms in CPS1 4217C>A and NAGS -3064C>A, on the development of
      hyperammonemia in Japanese pediatric epilepsy patients. The study included 177
      pediatric epilepsy patients. The presence of a 4217C>A polymorphism in CPS1 was
      determined using an allele-specific polymerase chain reaction (PCR)-based method,
      and the presence of a -3064C>A polymorphism in NAGS was determined using a PCR
      based restriction fragment length polymorphism method. Hyperammonemia was defined
      as a plasma ammonia level exceeding 200 MUg/dL. We observed a significant
      difference between the combination of valproic acid with phenytoin and the
      development of hyperammonemia in both univariate and multivariate analyses. With
      regard to the CPS1 4217C>A polymorphism, we did not observe a significant
      association with the development of hyperammonemia. In conclusion, CPS1 4217C>A
      polymorphism may not be associated with the development of hyperammonemia in
      Japanese population.

PMID- 24888249
TI  - First-principles calculation on oxygen ion migration in alkaline-earth doped
      La2GeO5.
AB  - By using first-principles calculations based on the density functional theory, we
      investigated the doping effects of alkaline-earth metals (Ba, Sr and Ca) in
      monoclinic lanthanum germanate La2GeO5 on its oxygen ion conduction. Although the
      lattice parameters of the doped systems changed due to the ionic radii mismatch,
      the crystal structures remained monoclinic. The contribution of each atomic
      orbital to electronic densities of states was evaluated from the partial
      densities of states and partial charge densities. It was confirmed that the
      materials behaved as ionic crystals comprising of cations of La and dopants and
      anions of oxygen and covalently formed GeO4. The doping effect on the activation
      barrier for oxygen hopping to the most stable oxygen vacancy site was
      investigated by the climbing-image nudged elastic band method. By tracing the
      charge density change during the hopping, it was confirmed that the oxygen motion
      is governed by covalent interactions. The obtained activation barriers showed
      excellent quantitative agreements with an experiment for the Ca- and Sr-doped
      systems in low temperatures as well as the qualitative trend, including the Ba
      doped system.

PMID- 24888248
TI  - Lamotrigine extended-release as adjunctive therapy with optional conversion to
      monotherapy in older adults with epilepsy.
AB  - PURPOSE: To determine the tolerability and efficacy of lamotrigine extended
      release (LTG XR) as adjunctive therapy with optional conversion to monotherapy in
      patients ages>=65 years with epilepsy. METHODS: This open-label study included
      the standard LTG XR dose escalation, an 8-week Adjunctive Maintenance Phase
      (AMP), a 13-week Adjunctive Optimization Phase or Conversion and Monotherapy
      Phase, and a Taper/Follow-Up Phase. At the end of the AMP, patients on a single
      concomitant antiepileptic drug (AED) were converted to LTG XR monotherapy over 5
      weeks and then remained in the Monotherapy Maintenance Phase for 8 weeks. All
      other patients remained in the study on concomitant AEDs for an additional 13
      weeks in the Adjunctive Optimization Phase. KEY FINDINGS: The number of patients
      who took >=1 dose of study medication was 121. Of the 92 patients completing the
      AMP, 68 patients (74%) were deemed by their treating physician to be eligible to
      proceed with monotherapy; the remaining 24 patients (26%) continued in the
      Adjunctive Optimization Phase. The types of adverse events reported with LTG XR
      were similar to those in studies of LTG XR in younger adult patients with
      epilepsy and studies of LTG immediate-release (IR) across age groups with
      epilepsy. No serious rashes were reported. For subjects who were not seizure free
      at baseline (n=55), the median baseline seizure frequency was 0.5 seizures per
      week. During the entire treatment period, the median percent change from baseline
      was 90% (p<0.0001). Fifty-two (52) patients (76%) of the 68 who entered the
      monotherapy phase successfully converted to monotherapy. SIGNIFICANCE: In this
      small open label study, LTG-XR was safe and effective when added to the AED
      regimen of older patients with epilepsy. Many patients were able to be converted
      to LTG-XR monotherapy.

PMID- 24888250
TI  - Impact of prompt catheter withdrawal and adequate antimicrobial therapy on the
      prognosis of hospital-acquired parenteral nutrition catheter-related bacteraemia.
AB  - Catheter-related bacteraemia (CRB) is a cause of death in hospitalized patients,
      and parenteral nutrition (PN) is a risk factor. We aim to describe the prognosis
      of PN-CRB and the impact of catheter extraction within 48 h from bacteraemia. All
      consecutive hospitalized adult patients with CRB (2007-2012) were prospectively
      enrolled. Factors associated with 30-day mortality were determined by logistic
      regression analysis. Among 847 episodes of CRB identified, 291 (34%) episodes
      were associated with short-term catheter use for PN. Cure was achieved in 236
      (81%) episodes, 42 (14.5%) patients died within the first 30 days, 7 (2.5%)
      relapsed, and 6 (2%) had re-infection. On multivariate analysis, previous
      immunosuppressive therapy (OR 5.62; 95% CI 1.69-18.68; p 0.0048) and patient age
      (OR 1.05; 95% CI 1.02-1.07; p 0.0009) were predictors of 30-day mortality,
      whereas catheter removal within 48 h of bacteraemia onset (OR 0.26; 95% CI 0.12
      0.58; p 0.0010) and adequate empirical antibiotic treatment (OR 0.36; 95% CI 0.17
      0.77; p 0.0081) were protective factors. Incidence of PN-CRB decreased from 5.36
      episodes/1000 days of PN in 2007 to 2.9 in 2012, yielding a 46.1% rate reduction
      (95% CI 15.7-65.5%), which may be attributable to implementation of a
      multifaceted prevention strategy. In conclusion, short-term PN-CRB accounted for
      one-third of all episodes of CRB in our setting, and 14.5% of patients died
      within 30 days following bacteraemia. Our findings suggest that prompt catheter
      removal and adequate empirical antibiotic treatment could be protective factors
      for 30-day mortality. Concomitantly with implementation of a multifaceted
      prevention strategy, PN-CRB incidence was reduced by half. 

PMID- 24888251
TI  - Epidural versus local anaesthetic infiltration via wound catheters in open liver
      resection: a meta-analysis.
AB  - BACKGROUND: This meta-analysis was designed to systematically analyse all
      published studies comparing local anaesthetic infiltration with wound catheters
      and epidural catheters in open liver resection. METHODS: A literature search was
      performed using the Cochrane Colorectal Cancer Group Controlled Trials Register,
      the Cochrane Central Register of Controlled Trials in the Cochrane Library,
      MEDLINE, Embase and Science Citation Index Expanded. Randomized trials, and
      prospective and retrospective studies comparing wound catheters with epidural
      catheters were included. Statistical analysis was performed using Review Manager
      Version 5.2 software. The primary outcome measures were pain scores in the post
      operative period operation. Secondary outcome measures were hospital stay, time
      to opening bowels, overall complications and analgesia-specific complications.
      RESULTS: Four studies including 705 patients were included in the analysis. The
      pain scores were significantly lower in those patients with epidural on the first
      post-operative day (POD) (mean difference of -0.90 [-1.29, -0.52], Z = 4.61) (P <
      0.00001) with comparable pain scores on PODs 2 and 3. There was no significant
      difference in the time to opening bowels, opioid use and hospital stay between
      the techniques. The post-operative complication rate was higher in the epidural
      group (risk ratio 1.40 [1.07, 1.83]; chi(2) = 0.60, df = 1) (P = 0.44); I(2) =
      0%; Z = 2.42 (P = 0.02). CONCLUSION: Local anaesthetic infiltration via wound
      catheters combined with patient-controlled opiate analgesia provides comparable
      pain relief to epidural catheters except for the first POD. Both techniques are
      associated with similar hospital stay and opioid use with wound catheters
      associated with lower complication rate.

PMID- 24888252
TI  - Hydroxycarbamide-induced cutaneous ulceration with a difference.

PMID- 24888253
TI  - Qualitative and quantitative prediction of volatile compounds from initial amino
      acid profiles in Korean rice wine (makgeolli) model.
AB  - In Korean rice wine (makgeolli) model, we tried to develop a prediction model
      capable of eliciting a quantitative relationship between initial amino acids in
      makgeolli mash and major aromatic compounds, such as fusel alcohols, their
      acetate esters, and ethyl esters of fatty acids, in makgeolli brewed. Mass
      spectrometry-based electronic nose (MS-EN) was used to qualitatively discriminate
      between makgeollis made from makgeolli mashes with different amino acid
      compositions. Following this measurement, headspace solid-phase microextraction
      coupled to gas chromatography-mass spectrometry (GC-MS) combined with partial
      least-squares regression (PLSR) method was employed to quantitatively correlate
      amino acid composition of makgeolli mash with major aromatic compounds evolved
      during makgeolli fermentation. In qualitative prediction with MS-EN analysis, the
      makgeollis were well discriminated according to the volatile compounds derived
      from amino acids of makgeolli mash. Twenty-seven ion fragments with mass-to
      charge ratio (m/z) of 55 to 98 amu were responsible for the discrimination. In GC
      MS combined with PLSR method, a quantitative approach between the initial amino
      acids of makgeolli mash and the fusel compounds of makgeolli demonstrated that
      coefficient of determination (R(2)) of most of the fusel compounds ranged from
      0.77 to 0.94 in good correlation, except for 2-phenylethanol (R(2) = 0.21),
      whereas R(2) for ethyl esters of MCFAs including ethyl caproate, ethyl caprylate,
      and ethyl caprate was 0.17 to 0.40 in poor correlation. PRACTICAL APPLICATION:
      The amino acids have been known to affect the aroma in alcoholic beverages. In
      this study, we demonstrated that an electronic nose qualitatively differentiated
      Korean rice wines (makgeollis) by their volatile compounds evolved from amino
      acids with rapidity and reproducibility and successively, a quantitative
      correlation with acceptable R2 between amino acids and fusel compounds could be
      established via HS-SPME GC-MS combined with partial least-squares regression. Our
      approach for predicting the quantities of volatile compounds in the finished
      product from initial condition of fermentation will give an insight to food
      researchers to modify and optimize the qualities of the corresponding products.

PMID- 24888254
TI  - Impact of regular physical activity on blood glucose control and cardiovascular
      risk factors in adolescents with type 2 diabetes mellitus--a multicenter study of
      578 patients from 225 centres.
AB  - INTRODUCTION: Regular physical activity (RPA) is a major therapeutic
      recommendation in children and adolescents with type 2 diabetes mellitus (T2DM).
      We evaluated the association between frequency of RPA and metabolic control,
      cardiovascular risk factors, and treatment regimes. METHODS: The Pediatric
      Quality Initiative (DPV), including data from 225 centers in Germany and Austria,
      provided anonymous data of 578 patients (10-20 yr; mean 15.7 +/- 2.1 yr; 61.9%
      girls) with T2DM. Patients were grouped by the frequency of their self-reported
      RPA per week: RPA 0, none; RPA 1, 1-2*/wk; RPA 2, >2*/wk. RESULTS: The frequency
      of RPA ranged from 0 to 9*/wk (mean 1.1*/wk +/-1.5). 55.7% of the patients
      reported no RPA (58.1% of the girls). Hemoglobin A1c (HbA1c) differed
      significantly among RPA groups (p < 0.002), being approximately 0.8 percentage
      points lower in RPA 2 compared to RPA 0. Body mass index (BMI-SDS) was higher in
      the groups with less frequent RPA (p < 0.00001). Multiple regression analysis
      revealed a negative association between RPA and HbA1c (p < 0.0001) and between
      RPA and BMI-SDS (p < 0.01). The association between RPA and high density
      lipoprotein (HDL)-cholesterol was positive (p < 0.05), while there was no
      association to total cholesterol, low density lipoprotein (LDL)-cholesterol or
      triglycerides. Approximately 80% of the patients received pharmacological
      treatment (oral antidiabetic drugs and/or insulin) without differences between
      RPA groups. CONCLUSION: More than half of the adolescents with T2DM did not
      perform RPA. Increasing physical activity was associated with a lower HbA1c, a
      lower BMI-SDS, a higher HDL-cholesterol, but not with a difference in treatment
      regime. These results suggest that regular exercise is a justified therapeutic
      recommendation for children and adolescents with T2DM.

PMID- 24888255
TI  - Distinct Prandial and Basal Glucose-Lowering Effects of Insulin Degludec/Insulin
      Aspart (IDegAsp) at Steady State in Subjects with Type 1 Diabetes Mellitus.
AB  - INTRODUCTION/AIM: Insulin degludec/insulin aspart (IDegAsp) is a soluble co
      formulation of long-acting and short-acting insulin analogs. The primary
      objective of this study was to investigate the pharmacodynamic response of once
      daily IDegAsp dosing in patients with type 1 diabetes. Pharmacokinetic response,
      as well as safety and tolerability, were assessed as secondary objectives.
      METHODOLOGY: This was a single-center, open-label, single-arm study. Twenty-two
      subjects received once-daily insulin degludec (IDeg) (0.42 U/kg) for five
      consecutive days [with separate bolus insulin aspart (IAsp) as needed for safety
      and glycemic control], to achieve clinical steady state of the basal component.
      On Day 6, they received a single injection of IDegAsp (0.6 U/kg, comprising 0.42
      U/kg IDeg and 0.18 U/kg IAsp). Pharmacodynamic response was assessed using a 30-h
      euglycemic glucose clamp, with blood glucose stabilized at a target of 5.5
      mmol/L. RESULTS: The glucose infusion rate profile showed a rapid onset of action
      and a distinct peak due to IAsp, followed by a separate, flat and stable basal
      glucose-lowering effect due to the IDeg component. Modeling data suggested that
      the pharmacodynamic profile of IDegAsp was retained with twice-daily dosing
      (allowing for coverage of two main meals daily). IDegAsp was well tolerated and
      no safety issues were identified in this trial. CONCLUSIONS: In conclusion, the
      IAsp component of IDegAsp has a fast onset of appearance and a peak covering the
      prandial phase, while the IDeg component has a flat and an evenly distributed
      pharmacokinetic profile over 24 h. IDegAsp is the first co-formulation of a basal
      insulin analog with an ultra-long duration of action and a mealtime insulin
      analog in a single soluble injection. These properties translate into clinically
      relevant benefits, including improved glycemic control and reduction in
      hypoglycemia.

PMID- 24888257
TI  - Idiopathic acquired unilateral breast atrophy in an adult woman.

PMID- 24888256
TI  - Sitagliptin Improves the Impaired Acute Insulin Response during a Meal Tolerance
      Test in Japanese Patients with Type 2 Diabetes Mellitus: A Small-Scale Real-World
      Study.
AB  - INTRODUCTION: Several studies have shown that dipeptidyl peptidase-4 (DPP-4)
      inhibitors improve insulin secretion during oral glucose tolerance tests.
      However, the effects of DPP-4 inhibitors on impaired acute insulin responses in
      the postprandial state in real-world settings are unknown. Therefore, we
      evaluated the effects of sitagliptin on the acute insulin responses in Japanese
      patients with type 2 diabetes mellitus (T2DM) using meal tolerance tests.
      METHODS: Twenty-one patients with T2DM were given a test meal (460 kcal), and
      plasma glucose and insulin were measured at 0, 30, 60, 120, and 180 min after the
      meal. The insulinogenic index of all of these patients was below 43.2. The
      postprandial profiles were assessed at baseline and after 3 months of treatment
      with 50 mg/day sitagliptin after a meal (n = 11) or were untreated (control
      group; n = 10). This study was a prospective, open-label, non-blinded, non
      randomized, clinical study. RESULTS: Sitagliptin significantly decreased the
      plasma glucose levels at 60, 120, and 180 min, and significantly increased the
      plasma insulin levels at 0 and 30 min. There were no significant changes in
      glucose or insulin in the control group. The insulinogenic index increased
      significantly in the sitagliptin group compared with the control group (+16.7 vs.
      +0.1, P < 0.005). However, homeostasis model assessment of insulin resistance and
      the insulin sensitivity index were not significant different between the two
      groups. CONCLUSION: Administration of sitagliptin at 50 mg/day after a meal
      improved the impaired acute insulin response and suppressed postprandial
      hyperglycemia. Whereas the study is rather small and the design is suboptimal as
      it is not randomized and not blinded, these results suggest that sitagliptin is
      effective in Japanese patients with T2DM, many of whom display impaired acute
      insulin responses after a meal.

PMID- 24888258
TI  - Clinical and economic impact of a switch from high- to low-volume renal
      replacement therapy in patients with acute kidney injury.
AB  - High-intensity renal replacement therapy protocols in intensive care patients
      with acute kidney injury have failed to translate to improved patient outcomes
      when compared with lower-intensity protocols. This retrospective study explored
      the clinical and economic impacts of switching from a 30-35 ml.kg(-1) .h(-1)
      (high-volume) to a 20 ml.kg(-1) .h(-1) (low-volume) protocol. Patients (n = 366)
      admitted 12 months before (n = 187) and after (n = 179) the switch were included
      in the study. There was no difference in in-hospital mortality (77/187 (41%) vs
      75/179 (42%), respectively, p = 0.92), intensive care unit mortality (55/187
      (29%) vs 61/179 (34%), respectively, p = 0.40), duration of organ support or
      extent of renal recovery between the high- and low-volume cohorts. A 25%
      reduction in daily replacement fluid usage was observed, equating to a cost
      saving of over L27 000 per annum. In conclusion, a switch from high- to low
      volume continuous haemodiafiltration had minimal effects on clinical outcomes and
      resulted in marked cost savings.

PMID- 24888259
TI  - Symposium report: the prevention of obesity and NCDs: challenges and
      opportunities for governments.
AB  - This paper is written as a briefing document with the aim of providing support to
      policy-makers and government officials tackling obesity and related non
      communicable diseases. It is based on a symposium Obesity and non-communicable
      diseases: Learning from international experiences convened by the International
      Association for the Study of Obesity (now the World Obesity Federation) and its
      policy section, the International Obesity TaskForce (now World Obesity - Policy
      and Prevention). The symposium discussed a wide range of proposals to tackle the
      consumption of unhealthy food products, including interventions in the market
      through fiscal policies and marketing restrictions, measures to strengthen public
      health legislation and measures to limit agri-food company lobbying activities.
      It recognized the need for government leadership and action in order to reduce
      preventable deaths while improving economic performance and identified a need for
      governments to take a systems wide approach to tackling obesity and to work with
      civil society, especially to monitor the drivers of disease and to hold all
      stakeholders accountable for progress. 

PMID- 24888260
TI  - Echocardiography in patients with adult congenital heart disease.

PMID- 24888263
TI  - Is thrombophilia associated with placenta-mediated pregnancy complications? A
      prospective cohort study: comment.

PMID- 24888261
TI  - Methods for SAXS-based structure determination of biomolecular complexes.
AB  - Measurements from small-angle X-ray scattering (SAXS) are highly informative to
      determine the structures of bimolecular complexes in solution. Here, current and
      recent SAXS-driven developments are described, with an emphasis on computational
      modeling. In particular, accurate methods to computing one theoretical scattering
      profile from a given structure model are discussed, with a key focus on structure
      factor coarse-graining and hydration contribution. Methods for reconstructing
      topological structures from an experimental SAXS profile are currently under
      active development. We report on several modeling tools designed for conformation
      generation that make use of either atomic-level or coarse-grained
      representations. Furthermore, since large, flexible biomolecules can adopt
      multiple well-defined conformations, a traditional single-conformation SAXS
      analysis is inappropriate, so we also discuss recent methods that utilize the
      concept of ensemble optimization, weighing in on the SAXS contributions of a
      heterogeneous mixture of conformations. These tools will ultimately posit the
      usefulness of SAXS data beyond a simple space-filling approach by providing a
      reliable structure characterization of biomolecular complexes under physiological
      conditions. 

PMID- 24888262
TI  - The frequency of rehospitalization and associated factors in Colombian
      psychiatric patients: a cohort study.
AB  - BACKGROUND: The rehospitalization of patients with mental disorders is common,
      with rehospitalization rates of up to 80% observed in these patients. This
      phenomenon negatively impacts families, patients, and the health care system.
      Several factors have been associated with an increased likelihood of
      rehospitalization. This study was aimed at determining the frequency and the
      factors associated with rehospitalization in a psychiatric clinic. METHODS: We
      performed a prospective cohort study with 361 patients who were hospitalized at
      the Clinic of Our Lady of Peace in Bogota, Colombia from August-December 2009. We
      calculated the incidence rates of rehospitalization and the risk factors using
      Cox regression. RESULTS: Overall, 60% of the patients in this cohort were
      rehospitalized during the year that followed the index event. The variables
      associated with rehospitalization were separated, divorced, or single status;
      higher socio-economic strata; a longer duration of index hospitalization; and a
      diagnosis of substance abuse, schizophrenia, bipolar disorder, or depression.
      CONCLUSIONS: The rehospitalization rate in our study was as high as reported in
      other studies. The associated factors with it in this group, may contribute to
      the design of programs that will reduce the frequency of rehospitalization among
      patients with mental disorders, in countries like Colombia. Additionally, these
      results may be useful in interventions, such as coping skills training, psycho
      education, and community care strategies, which have been demonstrated to reduce
      the frequency of rehospitalization.

PMID- 24888264
TI  - Photodynamic therapy for pododermatitis in penguins.
AB  - Pododermatitis is currently one of most frequent and important clinical
      complications in seabirds kept in captivity or in rehabilitation centers. In this
      study, five Magellanic penguins with previous pododermatitis lesions on their
      footpad were treated with photodynamic therapy (PDT). All PDT treated lesions
      successfully regressed and no recurrence was observed during the 6-month follow
      up period. PDT seems to be an inexpensive and effective alternative treatment for
      pododermatitis in Magellanic penguins encouraging further research on this topic.

PMID- 24888265
TI  - Personal determinants of nurses' burnout in end of life care.
AB  - PURPOSE: Our aim is to identify socio-demographic, professional exposure to
      dying, training degree and personal factors relevant to burnout dimensions in
      nurses coping with death issues. METHOD: A sample of 360 nurses (response rate
      70.6%) from internal medicine, oncology, haematology and palliative care
      departments of five health institutions answered to a socio-demographic and
      professional questionnaire, Maslach Burnout Inventory, Death Attitude Profile
      Scale, Purpose in Life Test and Adult Attachment Scale. RESULTS: No significant
      differences were found between medical departments in burnout scores except when
      comparing those with palliative care department which showed significant lesser
      levels of emotional exhaustion (t = 2.71; p < .008) and depersonalization (t =
      3.07; p < .003) and higher levels of personal accomplishment (t = -2.24; p <
      .027). By multiple regression analysis exhaustion and depersonalization are
      negative, sequentially determined respectively by purpose in life, dependent
      attachment, fear of death attitude and by purpose in life, dependent attachment,
      years of professional experience and personal accomplishment by positive purpose
      on life and secure attachment. CONCLUSION: We conclude for the protective value
      of factors such as meaning and purpose in life, secure attachment and attitude
      towards death, through the various burnout dimensions that shows the need to
      develop under and postgraduate training strategies in these specific areas.

PMID- 24888267
TI  - Increased activity correlates with reduced ability to mount immune defenses to
      endotoxin in zebra finches.
AB  - When suffering from infection, animals experience behavioral and physiological
      alterations that potentiate the immune system's ability to fight pathogens. The
      behavioral component of this response, termed "sickness behavior," is
      characterized by an overall reduction in physical activity. A growing number of
      reports demonstrate substantial flexibility in these sickness behaviors, which
      can be partially overcome in response to mates, intruders and parental duties.
      Since it is hypothesized that adopting sickness behaviors frees energetic
      resources for mounting an immune response, we tested whether diminished immune
      responses coincided with reduced sickness behaviors by housing male zebra finches
      (Taeniopygia guttata) in social conditions that alter their behavioral response
      to an endotoxin. To facilitate our data collection, we developed and built a
      miniaturized sensor capable of detecting changes in dorsoventral acceleration and
      categorizing them as different behaviors when attached to the finches. We found
      that the immune defenses (quantified as haptoglobin-like activity, ability to
      change body temperature and bacterial killing capacity) increased as a function
      of increased time spent resting. The findings indicate that when animals are sick
      attenuation of sickness behaviors may exact costs, such as reduced immune
      function. The extent of these costs depends on how relevant the affected
      components of immunity are for fighting a specific infection.

PMID- 24888266
TI  - The feasibility of a randomized controlled trial of esophagectomy for esophageal
      cancer--the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study:
      protocol for a randomized controlled trial.
AB  - BACKGROUND: There is a need for evidence of the clinical effectiveness of
      minimally invasive surgery for the treatment of esophageal cancer, but randomized
      controlled trials in surgery are often difficult to conduct. The ROMIO
      (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the
      feasibility of a main trial which will examine the clinical and cost
      effectiveness of minimally invasive and open surgical procedures for the
      treatment of esophageal cancer. METHODS/DESIGN: A pilot randomized controlled
      trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust
      and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible
      patients who consent to participate in the ROMIO study. Interventions will
      include esophagectomy by: (1) open gastric mobilization and right thoracotomy,
      (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally
      minimally invasive surgery (in the Bristol center only). The primary outcomes of
      the feasibility study will be measures of recruitment, successful development of
      methods to monitor quality of surgery and fidelity to a surgical protocol, and
      development of a core outcome set to evaluate esophageal cancer surgery. The
      study will test patient-reported outcomes measures to assess recovery, methods to
      blind participants, assessments of surgical morbidity, and methods to capture
      cost and resource use. ROMIO will integrate methods to monitor and improve
      recruitment using audio recordings of consultations between recruiting surgeons,
      nurses, and patients to provide feedback for recruiting staff. DISCUSSION: The
      ROMIO study aims to establish efficient methods to undertake a main trial of
      minimally invasive surgery versus open surgery for esophageal cancer. TRIAL
      REGISTRATION: The pilot trial has Current Controlled Trials registration number
      ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial
      record at that site gives a link to the original version of the study protocol.

PMID- 24888268
TI  - Should inpatients be adjusted by their complexity and severity for efficiency
      assessment? Evidence from Portugal.
AB  - Hospital efficiency analysis depends largely on the model specifications. This
      study discusses the importance of the case-mix index (CMI) to homogenize the
      sample of inpatient discharges. It proposes a new index where they are classified
      by service, since it is usual to have lack of data to compute the CMI and this
      can influence the credibility of results. Data from the Portuguese national
      diagnosis-related group (DRG) database was utilized. Three different approaches
      are developed in this paper, based on locally convex order-m method as well as on
      translog functions. The first one correlates the efficiency with different
      inpatients weighting schemes, by using the Nadaraya-Watson method. The second
      approach compares different frontiers that have been computed using the different
      weighting schemes. Finally, by using bootstrap, the paper investigates whether
      the inclusion of severity/ complexity-related variables in the model
      statistically modifies the results. It has been shown that, under the Portuguese
      healthcare framework, if the model is environment corrected (which should include
      epidemiological and main political/ structural health reforms variables), then
      the severity adjustment of inpatients is pointless. The employment of an
      inpatient-weighting scheme, such as the CMI, may introduce significant frontier
      shift, thus its absence is not recommended in productivity evolution analyzes.
      The CMI shifts the efficiency frontier, but not the relative position of units
      against it (the last scenario if exogenous variables are present). 

PMID- 24888269
TI  - Neurobiological changes after intervention in individuals with anti-social
      behaviour: a literature review.
AB  - BACKGROUND: A neurobiological perspective has become accepted as a valuable
      approach for understanding anti-social behaviour. There is literature to suggest
      that, in non-offending populations, psychological treatments affect both
      neurobiological measures and clinical presentation. A theoretical position to
      this effect has been adopted with respect to offender treatment, but there has
      been no systematic review of empirical literature on this point. AIMS: This study
      aimed to ascertain from published literature firstly whether there is evidence of
      change in neuropsychological or physiological measures after behavioural
      treatments/programmes for people with anti-social behaviour and secondly whether
      these neurobiological changes are associated with behavioural change. METHOD: A
      systematic search strategy was formulated to include studies considering
      'neurobiological factors', 'anti-social population', 'treatment' and 'treatment
      outcome'. The Maryland Scientific Methods Scale was used to select relevant
      studies of sufficient methodological quality. RESULTS: Eleven studies were found,
      only one with adults. Overall, the values of specific neurobiological risk
      factors, particularly of basal cortisol, become less abnormal following
      intervention. There was some evidence for a link between change in
      neurobiological functioning and behavioural improvement. CONCLUSIONS: Findings,
      although provisional, may provide new insights into the underlying mechanisms of
      interventions for anti-social behaviour. Future studies that include pre
      treatment neurobiological assessment could help reveal physical vulnerabilities
      that interventions should target to improve treatment efficacy, and provide for
      objective, independent corroboration of change.

PMID- 24888270
TI  - A computational model that predicts reverse growth in response to mechanical
      unloading.
AB  - Ventricular growth is widely considered to be an important feature in the adverse
      progression of heart diseases, whereas reverse ventricular growth (or reverse
      remodeling) is often considered to be a favorable response to clinical
      intervention. In recent years, a number of theoretical models have been proposed
      to model the process of ventricular growth while little has been done to model
      its reverse. Based on the framework of volumetric strain-driven finite growth
      with a homeostatic equilibrium range for the elastic myofiber stretch, we propose
      here a reversible growth model capable of describing both ventricular growth and
      its reversal. We used this model to construct a semi-analytical solution based on
      an idealized cylindrical tube model, as well as numerical solutions based on a
      truncated ellipsoidal model and a human left ventricular model that was
      reconstructed from magnetic resonance images. We show that our model is able to
      predict key features in the end-diastolic pressure-volume relationship that were
      observed experimentally and clinically during ventricular growth and reverse
      growth. We also show that the residual stress fields generated as a result of
      differential growth in the cylindrical tube model are similar to those in other
      nonidentical models utilizing the same geometry. 

PMID- 24888272
TI  - Essential thrombocythemia with high hemoglobin levels according to the revised
      WHO classification.

PMID- 24888271
TI  - Chimeric antigen receptor-redirected CD45RA-negative T cells have potent
      antileukemia and pathogen memory response without graft-versus-host activity.
AB  - Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive
      modality for cancer treatment. We hypothesized that allogeneic CAR-engineered
      CD45RA-negative T cells can control cancer and infection without the risk of
      graft-versus-host disease (GVHD). We used CD19(+) MLL-rearranged leukemia as
      prototype because it is an aggressive and generally drug-resistant malignancy.
      CD45RA(-) cells that were transduced with anti-CD19 CAR containing 4-1BB and
      CD3zeta signaling domains effectively lysed MLL-rearranged leukemia cell lines
      and primary blasts in vitro. In a disseminated leukemia mouse model,
      CAR(+)CD45RA(-) cells significantly reduced leukemia burdens and prolonged
      overall survival without GVHD. CAR(+) cells were sustainable in blood, and all
      the treated mice remained leukemia-free even after they were re-challenged with
      leukemia cells. Despite the transduction process, CD45RA(-) cells retained recall
      activity both in vitro and in vivo against human pathogens commonly found in
      cancer patients. In comparison with CD45RA(+) cells, CD45RA(-) cells showed less
      allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the
      use of CAR(+)CD45RA(-) cells can separate GVHD from graft-versus-malignancy
      effect and infection control. These cells should also be useful in nontransplant
      settings and may be administered as off-the-shelf third-party cells. 

PMID- 24888273
TI  - Early use of allogeneic hematopoietic stem cell transplantation for infants with
      MLL gene-rearrangement-positive acute lymphoblastic leukemia.
AB  - Sixty-two infants with MLL gene-rearrangement-positive acute lymphoblastic
      leukemia (MLL-r ALL) were treated with the MLL03 protocol of the Japanese
      Pediatric Leukemia/Lymphoma Study Group: short-course intensive chemotherapy
      followed by early allogeneic hematopoietic stem cell transplantation (HSCT)
      within 4 months of the initial induction. The 4-year event-free survival and
      overall survival rates were 43.2% (95% confidence interval (CI)=30.7-55.1%) and
      67.2% (53.8-77.4%), respectively. A univariate analysis showed younger age (<90
      days at diagnosis), central nervous system disease and poor response to initial
      prednisolone therapy significantly associated with poor prognosis (P<0.05). In a
      multivariate analysis, younger age at diagnosis tended to be associated with poor
      outcome (hazard ratio=1.969; 95% CI=0.903-4.291; P=0.088). Although the strategy
      of early use of HSCT effectively prevented early relapse and was feasible for
      infants with MLL-r ALL, the fact that substantial number of patients still
      relapsed even though transplanted in their first remission indicates the limited
      efficacy of allogeneic HSCT for infants with MLL-r ALL. Considering the risk of
      severe late effects, indications for HSCT should be restricted to specific
      subgroups with poor risk factors. An alternative approach incorporating molecular
      targeted drugs should be established. 

PMID- 24888276
TI  - The case report: Level 5 evidence, Level 1 medicine.

PMID- 24888274
TI  - Novel myelofibrosis treatment strategies: potential partners for combination
      therapies.
AB  - Of the myeloproliferative neoplasms (MPNs), myelofibrosis (MF) is associated with
      the greatest symptom burden and poorest prognosis and is characterized by
      constitutional symptoms, cytopenias, splenomegaly and bone marrow fibrosis. A
      hallmark of MF is dysregulation of the Janus kinase (JAK)/signal transducer and
      activator of transcription (STAT) pathway that has led to the development of JAK
      inhibitors targeting this pathway. Calreticulin gene mutations have recently been
      identified in JAK2 mutation-negative patients with MF. Identification of JAK
      inhibitor resistance and broad contributions to MF disease pathogenesis from
      epigenetic deregulators, pathways that work in concert with JAK/STAT (that is,
      mammalian target of rapamycin/AKT/phosphoinositide 3-kinase, RAS/RAF/MEK, PIM
      kinase), fibrosis-promoting factors and the MF megakaryocyte, suggest that
      numerous options may be partnered with a JAK inhibitor. Therefore, we will
      discuss logical and potential partners for combination therapies for the
      treatment of patients with MF.

PMID- 24888277
TI  - Randomised controlled trials: the long hard climb to the summit-is there another
      way in the 21st century?

PMID- 24888275
TI  - Comparison of minimal residual disease as outcome predictor for AML patients in
      first complete remission undergoing myeloablative or nonmyeloablative allogeneic
      hematopoietic cell transplantation.
AB  - Minimal residual disease (MRD) is associated with adverse outcome in acute
      myeloid leukemia (AML) after myeloablative (MA) hematopoietic cell
      transplantation (HCT). We compared this association with that seen after
      nonmyeloablative (NMA) conditioning in 241 adults receiving NMA (n=86) or MA
      (n=155) HCT for AML in first remission with pre-HCT bone marrow aspirates
      assessed by flow cytometry. NMA patients were older and had more comorbidities
      and secondary leukemias. Three-year relapse estimates were 28% and 57% for
      MRD(neg) and MRD(pos) NMA patients, and 22% and 63% for MA patients. Three-year
      overall survival (OS) estimates were 48% and 41% for MRD(neg) and MRD(pos) NMA
      patients and 76% and 25% for MA patients. This similar OS after NMA conditioning
      was largely accounted for by higher non-relapse mortality (NRM) in MRD(neg) (30%)
      compared with MRD(pos) (10%) patients, whereas the reverse was found for MRD(neg)
      (7%) and MRD(pos) (23%) MA patients. A statistically significant difference
      between MA and NMA patients in the association of MRD with OS (P<0.001) and NRM
      (P=0.002) but not relapse (P=0.17) was confirmed. After adjustment, the risk of
      relapse was 4.51 times (P<0.001) higher for MRD(pos) patients. These data
      indicate that the negative impact of MRD on relapse risk is similar after NMA and
      MA conditioning. 

PMID- 24888278
TI  - The accuracy of multidetector computed tomography in the diagnosis of non
      occlusive mesenteric ischaemia in patients after cardiovascular surgery.
AB  - OBJECTIVE: To determine the accuracy of multidetector computed tomography (MDCT)
      in the diagnosis of nonocclusive mesenteric ischaemia (NOMI) among patients after
      cardiovascular surgery. DESIGN, SETTING AND PARTICIPANTS: A retrospective review
      of 38 patients in a cardiothoracic intensive care unit who underwent MDCT
      examination before laparotomy for suspected NOMI between January 2001 and
      December 2012. INTERVENTION AND MAIN OUTCOME MEASURES: The MDCT studies were
      examined independently by three radiologists, who were asked to make a
      determination on the presence or absence of NOMI. The radiological diagnosis was
      compared against the surgical and/or histological outcome to determine the
      diagnostic accuracy of MDCT. RESULTS: The sensitivity and specificity of MDCT in
      the diagnosis of NOMI were 96% and 33%-60%, respectively. The positive and
      negative likelihood ratios and diagnostic odds ratio were 1.43-2.39, 0.072-0.13
      and 11-33.2, respectively. The inter-rater agreement was 68%, with a Fleiss kappa
      of 0.43. CONCLUSIONS: MDCT has high sensitivity but lacks specificity in the
      diagnosis of NOMI. Its main value is in selection of patients for non-operative
      management, at least in the short-to-medium term.

PMID- 24888279
TI  - Individual patient data meta-analysis of hydroxyethyl starch 130/0.4-0.42 versus
      crystalloid for fluid resuscitation in patients with severe sepsis: a statistical
      analysis plan.
AB  - BACKGROUND: The Crystalloid versus Hydroxyethyl Starch Trial (CHEST) and the
      Scandinavian Starch in Severe Sepsis/ Septic Shock (6S) trial reported that 6%
      hydroxyethyl starch (HES) is associated with increased use of renal replacement
      therapy and death in critically ill patients. Data collection was harmonised
      between the two trials in order to facilitate a preplanned individual patient
      data meta-analysis (IPDMA) of patients with severe sepsis. OBJECTIVES AND
      RATIONALE: To publish a statistical analysis plan (SAP) for an IPDMA of patients
      with severe sepsis enrolled in the 6S trial and the CHEST. METHODS AND OUTCOMES:
      The SAP is described in broad detail with specific information regarding baseline
      characteristics and process of care. The outcomes for the trial have been
      described and are presented as primary, secondary and exploratory outcomes with
      appropriate comparisons between groups detailed. Subgroups have been defined
      based on pre-randomisation variables. CONCLUSION: We developed a preanalysis SAP
      to combine data on patients with severe sepsis from the 6S trial and the CHEST.
      Prepublication of our SAP will reduce the risk of bias in the reporting of the
      results and improve confidence in the estimates of effects, allowing comparisons
      with conventional meta-analyses and assisting in the translation of research
      findings into clinical practice.

PMID- 24888280
TI  - Trends in intensive care unit cardiac arrest admissions and mortality in
      Australia and New Zealand.
AB  - OBJECTIVES: To develop methods for distinguishing patients with in-hospital
      cardiac arrest (IHCA) from patients with out-of-hospital cardiac arrest (OHCA) in
      routinely collected intensive care unit registry data, and to explore the utility
      of the methods for describing trends in adult ICU cardiac arrest (CA) admissions
      and outcomes. DESIGN AND SETTING: A retrospective observational analysis of all
      ICU admissions entered in the Australian and New Zealand Intensive Care Society
      adult patient database between 2000 and 2011. Trends in admission and survival
      rates to hospital discharge over time were examined using eight different methods
      of classifying patients with IHCA and OHCA. RESULTS: There were 1 001 754
      admissions to the ICUs between 2000 and 2011. Of these, postarrest admissions
      comprised 23 857 (2.4%), and increased annually by an average of 135 admissions
      (95% CI, 120-150 admissions). The annual volume of patients with IHCA as a
      fraction of total admissions declined by 0.4 patients/1000 admissions (95% CI,
      0.3-0.5 patients/1000 admissions). In contrast, for patients with OHCA, each year
      was associated with an additional 0.2 patients/1000 admissions (95% CI, 0.1-0.4
      patients/1000 admissions). This increase occurred in tertiary ICUs and declined
      in non-tertiary ICUs. Survival to hospital discharge for both groups improved,
      increasing annually by 1.2% (95% CI, 0.8%-1.6%) for patients with IHCA, and by
      1.1% (95% CI, 0.7%-1.4%) for patients with OHCA. CONCLUSIONS: Use of routinely
      collected registry data uncovered important trends in adult ICU admission and
      survival rates for patients with IHCA and OHCA. The improved survival rates and
      increased number of admissions to tertiary centres requires further study to
      understand mechanisms and related factors.

PMID- 24888281
TI  - Sodium administration in critically ill paediatric patients in Australia and New
      Zealand: a multicentre point prevalence study.
AB  - OBJECTIVE: Dysnatraemia and a positive fluid balance are associated with poor
      outcomes in paediatric intensive care units (PICUs). Our objective was to
      determine sodium intake and the total daily fluid balance in children in the
      PICU. METHOD: A single-day point prevalence study in 10 Australian and New
      Zealand PICUs. Patients on free oral diets were excluded. Demographics, 24-hour
      fluid balance and sodium intake (enteral and parenteral sources) were recorded.
      RESULTS: We enrolled 65 patients; 15 were excluded due to having a free oral
      intake and two patients had incomplete data, leaving 48 children in the study
      cohort. The 21 infants had a median age of 4 months (interquartile range [IQR], 1
      7 months) and a median bodyweight of 5 kg (IQR, 3.5- 6.1 kg). The 27 children > 1
      year had a median age of 3 years (IQR, 1.5-13 years) and a median bodyweight of
      17 kg (IQR, 9.5-47.5 kg). Overall, the median sodium administration on the study
      day was 4.9mmol/kg (IQR, 3.2- 8mmol/kg), median fluid administration was
      80.8mL/kg (IQR, 49.8-111.4mL/kg) and median fluid balance was 9mL/kg (IQR, -1.4
      to 41 mL/kg). For infants, the median sodium administration was 6mmol/kg (IQR,
      3.9-8.1mmol/ kg), and median fluid balance was 20.8mL/kg (IQR, 3.5- 47.2mL/kg).
      For children > 1 year, the median sodium administration was 3.5mmol/kg (IQR, 3.1
      7.8mmol/kg), and median fluid balance was 5.3mL/kg (IQR, -2.7 to 17.7mL/kg).
      Overall, fluid infusions, boluses and catheter flushes together contributed 46.2%
      of total sodium administered. Drugs contributed substantially to administered
      sodium (33.3%), with antibiotics accounting for the majority. Enteral feeds
      contributed 16.2% to overall administered sodium, and were the major source in
      patients in the PICU for > 10 days. CONCLUSION: Daily sodium intake in children
      in the PICU is high. The contributions of maintenance and bolus intravenous
      fluids (most commonly as 0.9% sodium chloride), drug infusions and boluses,
      including antibiotics, and enteral feeds, are significant.

PMID- 24888282
TI  - The mortality associated with review by the rapid response team for non-arrest
      deterioration: a cohort study of acute hospital adult patients.
AB  - OBJECTIVES: To compare the admission characteristics, discharge destination and
      mortality of patients reviewed by the rapid response team (RRT) for deterioration
      with those of other hospital patients; and to determine the association between
      RRT review for deterioration and mortality. DESIGN, SETTING AND PATIENTS: Acute
      admissions of adult patients to a tertiary hospital between 1 January 2008 and 31
      December 2011 were identified from administrative data. Data for each patient's
      first admission were merged with RRT data on the first RRT event of each
      admission, if any. RRT events involving cardiac arrest were classified as arrest
      events and all others as deterioration events. RESULTS: Of 43 385 patients in the
      cohort, 1117 (2.57%) had RRT review for deterioration and 91 (0.21%) for cardiac
      arrest. Deterioration events occurred a median of 3.23 days after admission.
      Advanced treatments were instituted in 38.59% of deterioration events, and a new
      not-for resuscitation order for 5.55%. Compared with those not reviewed by the
      RRT, patients in the deterioration group were older (median, 70 v 60 years, P <
      0.001) and had a higher Charlson comorbidity index (median, 1 v 0, P < 0.001).
      They also more often died in hospital (18.80% v 1.42%, P < 0.001) or were
      discharged to another hospital (37.51% v 13.39%, P < 0.001) and more often died
      in the 90 days after admission (24.44% v 3.48%, P < 0.001). Their adjusted odds
      ratio of death in the 90 days after admission was 5.85 (95% CI, 4.97-6.89, P <
      0.001). CONCLUSION: Patients reviewed for deterioration were older and had
      greater comorbidity than patients the RRT was not called to review. RRT review
      for deterioration was an independent risk factor for mortality.

PMID- 24888283
TI  - Vascular access site influences circuit life in continuous renal replacement
      therapy.
AB  - OBJECTIVE: To determine the influence of vascular access site on continuous renal
      replacement therapy (CRRT) filter survival. DESIGN, SETTING AND PATIENTS:
      Retrospective study of the records of patients who received CRRT in The Alfred
      intensive care unit from June 2011 to May 2012. MAIN OUTCOME MEASURE: Filter run
      time. METHODS: We matched filter run time to site and type of vascular access.
      Mean run times were compared using a linear mixed-effects model between:
      temporary femoral, internal jugular (IJ) and subclavian catheters, tunnelled
      semipermanent IJ catheters, and extracorporeal membrane oxygenation (ECMO)
      circuit access. The Markov chain Monte Carlo method was used to construct 95%
      confidence intervals, and the Wilcoxon rank sum test was used for post hoc
      testing of significance. RESULTS: Filter run-time data were available for 131
      patients (191 occasions of vascular access) with a total of 870 individual
      filters analysed. Mean run times were subclavian, 14.4 h; IJ, 17.1 h; femoral,
      20.2 h; tunnelled IJ, 25.2 h; and ECMO, 29.0 h. Differences were significant for
      all combinations except between subclavian and IJ, and between tunnelled access
      and ECMO. Sites in order of best performing to worst-performing were ECMO
      circuit, tunnelled IJ, femoral vein, direct IJ vein, and subclavian vein.
      CONCLUSION: Vascular access for CRRT plays a significant role in determining
      filter life. Our study suggests that for temporary dialysis catheters the femoral
      site should be favoured in ICU patients, and if CRRT is likely to continue for an
      extended period, a tunnelled IJ line should be considered.

PMID- 24888285
TI  - Intensivists under threat: who's in charge here?
AB  - The model currently used in public hospitals in Australia and New Zealand - of
      closed, mixed medical-surgical ICUs, led by consultant intensivists who remain in
      charge but collaborate closely across multiple specialties and disciplines and
      are supported by well trained junior medical staff- is internationally admired
      and has provided cost-effective care. Careful workforce planning is essential to
      ensure that intensivists retain their identity and that an efficient model
      persists into the future.

PMID- 24888284
TI  - Randomised trial of software algorithm driven regional citrate anticoagulation
      versus heparin in continuous renal replacement therapy: the Filter Life in Renal
      Replacement Therapy pilot trial.
AB  - OBJECTIVE: The effectiveness of continuous renal replacement therapy (CRRT)
      increases when unplanned circuit failure is prevented. Adequate anticoagulation
      is an important component. Although heparin is the predominating anticoagulant,
      calcium chelation with citrate is an alternative, but systemic calcium monitoring
      and supplementation increase the complexity of CRRT. We assessed efficacy and
      safety of citrate delivery via integrated software algorithms against an
      established regional heparin protocol. DESIGN: Prospective computer randomisation
      allocated eligible patients to regional citrate or heparin between April and
      December 2012. Citrate fluids were Prismocitrate 18 mmol/L predilution and
      Prism0cal B22 dialysate. Hemosol B0 was the default fluid for heparin. The
      primary outcome was filter running time. Electively terminated circuits were
      censored. Intention-totreat (ITT) and per-protocol analyses were performed.
      Filter survival was compared by log-rank tests and hazard ratios were explored
      with a mixed-effects Cox model. RESULTS: 221 filters were analysed from 30
      patients (of whom 19 were randomly allocated to citrate filters and 11 to heparin
      filters). Patients randomly allocated to citrate were older, sicker, with a
      higher male:female ratio, but of similar weight. Mortality was 37% in the citrate
      arm and 27% in the heparin arm. All deaths were attributed to underlying disease.
      Significant crossover occurred from the citrate arm to use of heparin. Median
      filter survival, by ITT, was not significantly different (citrate, 34 hours;
      heparin, 30.7 hours; P=0.58). Per-protocol survival favoured citrate (citrate,
      42.1 hours; heparin, 24 hours; chi(2)=8.1; P=0.004). Considerable variation in
      filter life existed between patients, and between vascular access sites within
      patients. Safety end points were reached in one heparin and three citrate
      patients. CONCLUSION: Although the per-protocol results favoured citrate when it
      was actually delivered, the significant crossover between treatment arms hampered
      more definitive conclusions. Until further studies support improved patient
      outcomes, increased complexity and complications suggest that anticoagulation
      choice be made using patient-specific indications.

PMID- 24888289
TI  - A survey of self-reported management of hypernatraemia acquired in Australasian
      intensive care units.
AB  - OBJECTIVE: To examine self-reported treatment preferences among Australasian
      consultant intensivists for intensive care-acquired hypernatraemia (IAH). DESIGN
      AND SETTING: We used a web-based survey with 10 questions about the management of
      IAH. MAIN OUTCOME MEASURES: We measured number of respondents and response rate,
      IAH treatment methods, thresholds and the reasons for these. RESULTS: There were
      156 survey respondents, of whom 137 were consultant intensivists, representing a
      response rate of 31%. Ninety-three percent of responding clinicians (95% CI, 87%
      96%) used intravenous fluid (49%; 95% CI, 40%-57%) or enteral nutrition changes
      (44%; 95% CI, 36%-53%) as their first choice of treatment. As alternative
      therapies, respondents reported using thiazides (22%; 95% CI, 16%-30%),
      aldosterone antagonists (20%; 95% CI, 14%-28%) and renal replacement therapy
      (14%; 95% CI, 9%-21%) less commonly. CONCLUSIONS: There is a wide variety of
      treatments in use for IAH. Most clinicians initiate treatment at a level greater
      than the level that is independently associated with increased mortality in the
      literature.1 Initial treatment is equally divided between changes in intravenous
      fluid and changes in enteral nutrition.

PMID- 24888290
TI  - Informed consent for procedures in the intensive care unit: ethical and practical
      considerations.
AB  - There is increasing interest in procedural consent (informed consent for invasive
      procedures) in the intensive care unit. We reviewed studies of procedural consent
      and show that it is not yet routine practice to obtain consent before performing
      invasive procedures on ICU patients. We considered logistical barriers to
      procedural consent in the critical care environment and the ethical implications
      of introducing routine procedural consent to the ICU. 

PMID- 24888292
TI  - "Being a doctor" - and some further pedantry.

PMID- 24888291
TI  - An age-of-blood transfusion trial in the trauma setting is crucial and animal
      models may help inform trial design.

PMID- 24888296
TI  - Is national socioeconomic status related to prevalence of irritable bowel
      syndrome?
AB  - BACKGROUND AND AIM: There are a multitude of cross-sectional surveys that provide
      the prevalence of irritable bowel syndrome (IBS) in the community. However, the
      data regarding the influence of socioeconomic status on prevalence of IBS were
      sparse. This study is to investigate the possible relation between human
      development and prevalence of IBS, at national level. METHODS: EMBASE Classic,
      EMBASE, and MEDLINE were searched (until October 2013) to identify population
      based studies that reported prevalence of IBS. Human Development Index (HDI) was
      chosen to assess socioeconomic status at national level. RESULTS: Firstly, no
      correlation was observed between prevalence of IBS and national HDI (P = 0.848).
      Specifically, there was no statistical significance in prevalence between
      developing and developed countries (P = 0.319). Moreover, prevalence of IBS
      failed to witness a downtrend in worldwide over the past two decades.
      Interestingly, the ratio of female/male prevalence was correlated with national
      HDI according to linear regression analysis (r = 0.395), and the ratio in the
      developing was significant lower than that in the developed (P = 0.0394). Lastly,
      except methods of data collection (P < 0.000), it shows no difference between
      developing and developed countries in diagnostic criteria, IBS subtypes, and age
      distribution (P = 0.119, 0.327, and 0.845 respectively). CONCLUSIONS: This study
      is the first time to investigate the relation between IBS prevalence and national
      socioeconomic status, with consideration of years, gender, and other factors. It
      demonstrates that national development is not a direct indicator for prevalence
      of IBS.

PMID- 24888298
TI  - Molecular dynamics study of the effect of alkyl chain length on melting points of
      [CnMIM][PF6] ionic liquids.
AB  - Based on molecular dynamics simulations, the melting points Tm of a series of 1
      alkyl-3-methylimidazolium hexafluorophosphate ionic liquids [CnMIM][PF6] with n =
      2, 4, 10, 12, and 14 were studied using the free energy-based pseudosupercritical
      path (PSCP) method. The experimental trend that the Tm decreases with increasing
      alkyl chain length for ILs with short alkyl chains and increases for the ones
      with long alkyl chains was correctly captured. Further analysis revealed that the
      different trends are the results of the balance between fusion enthalpy and
      fusion entropy. For the ILs with short alkyl chains (ethyl and butyl groups),
      fusion entropy plays the dominant role so that [C4MIM][PF6], which has a larger
      fusion entropy due to its higher liquid phase entropy has the lower melting
      temperature. As for the ILs with long alkyl chains, due to the enhanced van der
      Waals interactions brought about by the long non-polar alkyl chains, enthalpy
      becomes the deciding factor and the melting points increase when the alkyl chain
      goes from C10 to C14. While the melting points for [C2MIM][PF6] and [C4MIM][PF6]
      were quantitatively predicted and the trends for the long chain ILs were captured
      correctly, the absolute melting points for [C10MIM][PF6], [C12MIM][PF6] and
      [C14MIM][PF6] were systematically overestimated in the simulations. Three
      possible reasons for the overestimation were studied but all ruled out. Further
      simulation or experimental studies are needed to explain the difference. 

PMID- 24888297
TI  - Diversity in early crustal evolution: 4100 Ma zircons in the Cathaysia Block of
      southern China.
AB  - Zircons are crucial to understanding the first 500 Myr of crustal evolution of
      Earth. Very few zircons of this age (>4050 Ma) have been found other than from a
      ~300 km diameter domain of the Yilgarn Craton, Western Australia. Here we report
      SIMS U-Pb and O isotope ratios and trace element analyses for two ~4100 Ma
      detrital zircons from a Paleozoic quartzite at the Longquan area of the Cathaysia
      Block. One zircon ((207)Pb/(206)Pb age of 4127 +/- 4 Ma) shows normal oscillatory
      zonation and constant oxygen isotope ratios (delta(18)O = 5.8 to 6.00/00). The
      other zircon grain has a ~4100 Ma magmatic core surrounded by a ~4070 Ma
      metamorphic mantle. The magmatic core has elevated delta(18)O (7.2 +/- 0.20/00),
      high titanium concentration (53 +/- 3.4 ppm) and a positive cerium anomaly,
      yielding anomalously high calculated oxygen fugacity (FMQ + 5) and a high
      crystallization temperature (910 degrees C). These results are unique among
      Hadean zircons and suggest a granitoid source generated from dry remelting of
      partly oxidizing supracrustal sediments altered by surface waters. The ~4100 Ma
      dry melting and subsequent ~4070 Ma metamorphism provide new evidence for the
      diversity of the Earth's earliest crust. 

PMID- 24888299
TI  - Social media and communication.

PMID- 24888295
TI  - Puberty and the manifestations of loss of control eating in children and
      adolescents.
AB  - OBJECTIVE: We investigated the manifestations of pediatric loss of control (LOC)
      eating at different stages of pubertal development. METHOD: Participants were a
      nonclinical sample of 468 youth (8-17 years). Physical examination determined
      pubertal stage. LOC eating and disordered eating attitudes were assessed with the
      Eating Disorder Examination. In a randomized crossover design, a subset (n = 244)
      ate ad libitum from two test meals designed to capture normal and LOC eating.
      RESULTS: There were no differences in the prevalence rates or frequency of
      reported LOC eating episodes across pubertal stages (ps >= 0.50). There were,
      however, puberty by LOC eating interactions in disordered eating attitudes and
      palatable food consumption (ps <= .05), even after adjusting for age and body
      composition. LOC eating was associated with elevated global disordered eating
      attitudes, weight concern, and shape concern in post-pubertal youth (ps <= .001),
      but not pre-pubertal youth (ps >= .49). In late-puberty, youth with LOC eating
      consumed less energy from protein (p < .001) and more from carbohydrate (p =
      .003) and snack-type foods (p = .02) than those without LOC eating, whereas
      endorsement of LOC eating in pre- or early-to-mid-puberty was not associated with
      differences in eating behavior (ps >= 0.20). CONCLUSIONS: Findings suggest that
      puberty may be a critical risk period, when LOC eating behaviors in boys and
      girls may become accompanied by greater weight and shape concerns and more
      obesogenic food consumption patterns. Interventions for LOC eating during pre
      puberty should be evaluated to determine if they are particularly beneficial for
      the prevention of exacerbated eating disorder psychopathology and adverse weight
      outcomes.

PMID- 24888304
TI  - Multiple congenital nevi in a newborn.

PMID- 24888305
TI  - A case of late presentation of developmental dysplasia of the hip with normal
      screening ultrasound scan.

PMID- 24888306
TI  - A day on the paediatric wards in Port Moresby, Papua New Guinea.

PMID- 24888307
TI  - Audit of tetanus immunization status in paediatric burn patients.

PMID- 24888308
TI  - Social media in medicine.

PMID- 24888309
TI  - Development of clinical pharmacology as a medical speciality in Europe - the
      roles of WHO, IUPHAR and EACPT.
AB  - This MiniReview shows that both WHO and IUPHAR very early recognized that there
      is a gap between the availability of academic expert knowledge in pharmacology
      and its utilization in health care. Many initiatives have been taken to bridge
      this gap, but still 12 European countries do not recognize clinical pharmacology
      as a medical speciality because the profession has failed to develop defined
      functions in patient care. A first priority for EACPT therefore ought to be to
      promote clinical pharmacology as a medical speciality recognized by the European
      Union. The pharmacological services listed in Table 7 that focus on drug problems
      agree well with those that were recently prioritized in the IUPHAR/WHO/CIOMS
      manifesto to correct a major weakness in the health care of today in order to
      promote rational use of drugs. 

PMID- 24888310
TI  - Prevalence of human bocavirus 1 among people without gastroenteritis symptoms in
      South Korea between 2008 and 2010.
AB  - To investigate the prevalence of human bocavirus (HBoV) among people without
      gastroenteritis symptoms in South Korea between 2008 and 2010, an epidemiological
      study was performed on fecal samples of 320 people aged 2 months to 91 years. The
      prevalence of HBoV-1 was 12.5 % (40/320) of the study population by PCR. Co
      infection with adenovirus was found in six samples (1.9 %). According to
      nucleotide sequence analysis, all 40 Korean HBoVs strains belonged to the HBoV-1
      group and showed high sequence identity to each other, ranging from 94.3-99.7 %.
      These findings suggest that HBoV-1 is highly prevalent across age groups among
      people without gastroenteritis symptoms.

PMID- 24888311
TI  - Foot-and-mouth disease virus low-fidelity polymerase mutants are attenuated.
AB  - Previous studies have shown that RNA viruses can be attenuated by either
      increased or decreased viral polymerase replication fidelity. Although foot-and
      mouth disease virus (FMDV) high-fidelity RNA-dependent RNA polymerase (RdRp)
      variants with an attenuated phenotype have been isolated using mutagens, no FMDV
      mutant with a low-fidelity polymerase has been documented to date. Here, we
      describe the generation of several FMDV RdRp mutants using site-directed
      mutagenesis via a reverse genetic system. Mutation frequency assays confirmed
      that five rescued FMDV RdRp mutant populations had lower replication fidelity
      than the wild-type virus population, which allowed us to assess the effects of
      the change in replication fidelity on the virus phenotype. These low-fidelity
      FMDV RdRp mutants showed increased sensitivity to ribavirin or 5-fluorouracil (5
      FU) treatment without a loss of growth capacity in cell cultures. In addition,
      decreased fitness and attenuated virulence were observed for the RdRp mutants
      with lower fidelity. Importantly, based on a quantitative analysis for fidelity
      and virulence, we concluded that lower replication fidelity is associated with a
      more attenuated virus phenotype. These results further contribute to our
      understanding of the replication fidelity of polymerases of RNA viruses and its
      relationship to virulence attenuation.

PMID- 24888312
TI  - A vesicular stomatitis pseudovirus expressing the surface glycoproteins of
      influenza A virus.
AB  - Pseudotyped viruses bearing the glycoprotein(s) of a donor virus over the
      nucleocapsid core of a surrogate virus are widely used as safe substitutes for
      infectious virus in virology studies. Retroviral particles pseudotyped with
      influenza A virus glycoproteins have been used recently for the study of
      influenza hemagglutinin and neuraminidase-dependent processes. Here, we report
      the development of vesicular-stomatitis-virus-based pseudotypes bearing the
      glycoproteins of influenza A virus. We show that pseudotypes bearing the
      hemagglutinin and neuraminidase of H5N1 influenza A virus mimic the wild-type
      virus in neutralization assays and sensitivity to entry inhibitors. We
      demonstrate the requirement of NA for the infectivity of pseudotypes and show
      that viruses obtained with different NA proteins are significantly different in
      their transduction activities. Inhibition studies with oseltamivir carboxylate
      show that neuraminidase activity is required for pseudovirus production, but not
      for the infection of target cells with H5N1-VSV pseudovirus. The HA-NA-VSV
      pseudoviruses have high transduction titers and better stability than the
      previously reported retroviral pseudotypes and can replace live influenza virus
      in the development of neutralization assays, screening of potential antivirals,
      and the study of different HA/NA reassortants.

PMID- 24888313
TI  - Update in the diagnosis and management of transthyretin familial amyloid
      polyneuropathy.
AB  - Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a progressive
      neurodegenerative and systemic genetic disease first identified in Portugal, now
      reported worldwide. During the past few years our knowledge on the phenotypic
      presentation of this devastating condition has remarkably expanded including a
      wide variation in age of onset, different neuropathic patterns and patients
      presenting with isolated or predominant cardiac involvement. Liver
      transplantation, the first therapeutic approach, although invasive, has been
      shown to halt the progression of the neuropathy in young onset patients.
      Fortunately, several disease-modifying treatments are now available or in
      clinical development including TTR stabilizers and gene therapy. Their efficacy
      is higher if administered at the earliest disease stage. Thus, management of TTR
      FAP patients is a moving field with need for early diagnosis using new diagnostic
      tools and new therapeutic options. 

PMID- 24888314
TI  - Stroke in sports: a case series.
AB  - Regular physical activity decreases vascular risk. However, vascular events,
      including stroke, can occur while practicing physical activities. Stroke
      associated with sports is a rare clinical entity, whose risk factors and
      mechanisms are not fully understood. We report a case series of sports-related
      stroke, from tertiary care institutions. From the stroke registries of two
      University Neurology services and Stroke Units we retrieved all cases of stroke
      which occurred in temporal association with the practice of sports. Investigators
      had to fill a simple case report form, describing the demographic, clinical
      characteristics of the patients and the sport associated with the stroke. We
      included ten patients aged between 27 and 65 years, 8 being male. Only three
      subjects had vascular risk factors. Trauma to the head and/or neck was reported
      in two patients only. Cervicocerebral arterial dissection was the main cause of
      stroke, occurring in six of the ten cases. No patient died, but three were left
      disabled (modified Rankin Scale 3-5). This case series confirms that stroke
      associated with sport is very rare. The majority of the victims did not have
      vascular risk factors. Dissection was the most common cause of sport-associated
      stroke. Strokes were often disabling.

PMID- 24888315
TI  - Clinical outcomes of two main variants of progressive supranuclear palsy and
      multiple system atrophy: a prospective natural history study.
AB  - Progressive supranuclear palsy (PSP) and parkinsonian subtype of multiple system
      atrophy (MSA-P) are, after Parkinson's disease (PD), the most common forms of
      neurodegenerative parkinsonism. Clinical heterogeneity of PSP includes two main
      variants, Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P). Clinical
      differentiation between them may be impossible at least during the first 2 years
      of the disease. Little is known about the differences in natural course of PSP-RS
      and PSP-P and, therefore, in this study we prospectively followed the clinical
      outcomes of consecutive, pathologically unconfirmed patients with the clinical
      diagnoses of PSP-RS (51 patients), PSP-P (21 patients) and MSA-P (49 patients).
      Estimated mean survival time was 11.2 years for PSP-P, 6.8 years for PSP-RS, and
      7.9 years for MSA-P, where a 5-year survival probabilities were 90, 66 and 78 %,
      respectively. More disabling course of PSP-RS compared to PSP-P was also
      highlighted through the higher number of milestones reached in the first 3 years
      of the disease, as well as in the trend to reach all clinical milestones earlier.
      We found that PSP-P variant had a more favorable course with longer survival, not
      only when compared to PSP-RS, but also when compared to another form of atypical
      parkinsonism, MSA-P.

PMID- 24888316
TI  - Effect of myrtle fruit syrup on abnormal uterine bleeding: a randomized double
      blind, placebo-controlled pilot study.
AB  - BACKGROUND: Myrtle (Myrtus communis L.) has been used in the Iranian Traditional
      Medicine as a treatment for abnormal uterine bleeding-menometrorrhagia. The main
      aim of this study is to evaluate the effect of myrtle fruit syrup on abnormal
      uterine bleeding-menometrorrhagia. METHODS: A randomized, double-blind, placebo
      controlled pilot study was conducted on 30 women suffering from abnormal uterine
      bleeding-menometrorrhagia. Treatment comprised of giving 15 ml oral myrtle syrup
      daily (5 ml three times a day) for 7 days starting from the onset of bleeding.
      The myrtle syrup along with placebo was repeated for 3 consecutive menstrual
      periods. Menstrual duration and number of used pads were recorded by the
      Pictorial Blood loss Assessment Chart at the end of each menstrual period. The
      quality of life was also evaluated using the menorrhagia questionnaire. RESULTS:
      The mean number of bleeding days significantly declined from 10.6 +/- 2.7 days to
      8.2 +/- 1.9 days after 3 months treatment with the syrup (p = 0.01) and
      consequently the participants in the intervention group used fewer pads after 3
      months (16.4 +/- 10.7) compared with the number of pads used at the beginning of
      the treatment (22.7 +/- 12.0, p = 0.01). Bleeding days and number of pads used by
      the participants in the placebo group did not change significantly. Also
      significant changes of quality of life scores were observed in the intervention
      group after 3 months compared to the baseline. CONCLUSION: Myrtle syrup is
      introduced as a potential remedy for abnormal uterine bleeding-menometrorrhagia.

PMID- 24888317
TI  - Mixtures of recombinant growth factors inhibit the production of pro-inflammatory
      mediators and cytokines in LPS-stimulated RAW 264.7 cells by inactivating the ERK
      and NF-kappaB pathways.
AB  - Growth factors are important for regulating a variety of cellular processes and
      typically act as signaling molecules between cells. In the present study, we
      examined the mechanisms underlying the inhibitory effects of mixtures of
      recombinant growth factors (MRGFs) on nitric oxide (NO) and pro-inflammatory
      cytokine production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. We
      also examined whether these effects are mediated through the mitogen-activated
      protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) signal transduction
      pathways. NO production was assessed by measuring nitrite acucmulation using the
      Greiss reaction. Cytokine concentrations were measured using respective ELISA
      kits for each cytokine. Our results revealed that the MRGFs significantly
      attenuated the LPS-induced production of pro-inflammatory cytokines and NO in a
      dose-dependent manner. To elucidate the mechanisms underlying the inhibitory
      effects of MRGFs, we examined the effects of the LPS-induced phosphorylation of
      MAPKs and the activation of the NF-kappaB signaling pathway on the stabilization
      of NF-kappaB nuclear translocation and inhibitory factor-kappaB (IkappaB)
      degradation. Western blot analysis was performed to determine the total and
      phosphorylated levels of ERK, as well as the nuclear translocation of NF-kappaB,
      and IkappaB phosphorylation and degradation. Our results demonstrated that
      treatment with MRGFs resulted in a reduction in the phosphorylation of the ERK
      and NF-kappaB signaling pathways, whereas the phosphorylation of JNK and p38 was
      not affected. Taken together, our results suggest that MRGFs inhibit the
      production of pro-inflammatory cytokines and NO by downregulating inducible NO
      synthase gene expression and blocking the phosphorylation of the ERK and NF
      kappaB signaling pathways. These findings may provide direct evidence of the
      potential application of MRGFs in the prevention and treatment of inflammatory
      diseases.

PMID- 24888318
TI  - Chemoenzymatic synthesis of functional sialyl Lewis(x) mimetics with a
      heteroaromatic core.
AB  - Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the
      enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which
      was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using
      the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding
      of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl
      Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at
      low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed
      higher activities than the natural tetrasaccharide. 

PMID- 24888319
TI  - Effect of HMGB1 on the paracrine action of EPC promotes post-ischemic
      neovascularization in mice.
AB  - Transplantation of endothelial progenitor cells (EPCs) leads to better outcomes
      in experimental stroke, but the mechanism remains unclear. It was reported that
      astrocytic-high mobility group box1 (HMGB1) promoted endogenous EPC-mediated
      neurovascular remodeling during stroke recovery. It is unclear whether HMGB1
      involves in exogenous EPC-mediated stroke recovery. In this study, we aim to
      explore whether microglial HMGB1 contributes to human peripheral blood-derived
      (hPB)-EPCs-mediated neurovascular remodeling by modulating the paracrine function
      of exogenous hPB-EPCs. Coculturing hPB-EPCs with lipopolysaccharides stimulated
      BV2 cells upregulated Interleukin-8 expression in hPB-EPCs; this was blocked by
      treating BV2 cells with HMGB1 inhibitor Glycyrrhizin. Conditioned medium (CM) of
      hPB-EPCs cocultured with BV2 cells promoted the viability and tube formation of
      human umbilical cord vein cells. Inhibiting either HMGB1 or IL-8 could block the
      effect of hPB-EPCs CM. In vivo study showed hPB-EPCs transplantation improved
      neurobehavioral outcomes, reduced brain atrophy volume, and enhanced
      neovascularization in transient middle cerebral artery occlusion (tMCAO) mice.
      Intraperitoneally administration of HMGB1 inhibitor glycyrrhizin blocked the
      beneficial effect of hPB-EPC transplantation. We did not observe the integration
      of green fluorescent protein-labeled hPB-EPCs with microvessels in peri-infarct
      areas at day-14 after tMCAO. In summary, the result suggested that HMGB1
      upregulation in postischemic brain could promote exogenous hPB-EPC-mediated
      stroke recovery by modulating paracrine function of hPB-EPCs.

PMID- 24888320
TI  - Wuchereria bancrofti 20/22 a homologue of abundant larval transcript L3 stage
      filarial antigen: molecular and immunological characterization.
AB  - The chromadorea abundant larval transcript (ALT) family of proteins contains ALT
      one of the most studied putative vaccine candidate in experimental filariasis.
      This study reports the characterization of Wuchereria bancrofti 20/22 (Wb20/22)
      as a member of chromadorea, the ALT family of proteins from the L3 stage of W.
      bancrofti. The high reactivity with serum from the endemic normal (EN) population
      suggests that Wb20/22 could be a target of elicit protective immunity. The
      glutamic acid-rich region of Wb20/22 was predicted to harbour the longest linear
      B-cell epitope by insilico prediction tools. The significance of this region was
      revealed by studying the mutant form of Wb20/22, without acidic domain (WOAD)
      which was cloned, and the immune response was compared with Wb20/22. The signal
      sequence of Wb20/22 was also an immunodominant region, and mutant construct
      without signal sequence (WOSS) was cloned and characterized. The peak antibody
      titre elicited by WOAD was higher than Wb20/22 or WOSS, which pointed to the
      immunomodulatory role of glutamic acid-rich region. Wb20/22 elicited very high
      levels of IL-10 and diminished levels of IL-4 and IL-5 which could be the reason
      for low antibody titre. The prophylactic efficacy of WOAD conferred protection
      (62.26%) which was higher than Wb20/22 (49.82%) and WOSS (54.78%).

PMID- 24888321
TI  - Carinal resection and reconstruction in thoracic malignancies.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to present clinical
      outcomes of malignant tumors involving the carina after surgery in order to
      establish the management guidelines. METHODS: Between 1996 and 2011, 30 patients
      underwent carinal resection and reconstruction for malignancy involving carina.
      We retrospectively analyzed their medical records. There were 22 cases of common
      type of NSCLC (squamous cell carcinoma/adenocarcinoma/large cell neuroendocrine
      carcinoma) and eight cases of carcinomas of salivary gland type (adenoid cystic
      carcinoma/mucoepidermoid carcinoma). RESULTS: Seventeen right sleeve
      pneumonectomies, two left sleeve pneumonectomies, nine carinal sleeve right upper
      lobectomies, and two airway resections and reconstructions without lung resection
      were performed. There were no in-hospital mortalities. Eleven postoperative
      morbidities occurred including three cases of acute respiratory distress syndrome
      following pneumonectomy. Late complications occurred in eight patients including
      three cases of anastomotic stenosis. During follow-up, 12 mortalities occurred,
      including 6 cancer-related mortalities. The 5-year overall survival rate (OS) and
      disease-free survival rate (DFS) were 66.3% and 52.9%, respectively. CONCLUSIONS:
      Malignant tumors involving the carina can be controlled with carinal surgery with
      acceptable mortality and morbidity. Patients with thoracic malignancy involving
      the carina should be considered as surgical candidate based on disease extent and
      functional status.

PMID- 24888322
TI  - Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental
      model.
AB  - OBJECTIVE AND DESIGN: Mesenchymal stem cells (MSCs) are potent modulators of
      immune responses. Sepsis is the association of a systemic inflammatory response
      with an infection. The aim of this study was to test the ability of MSCs derived
      from adipose tissue, which have immunomodulatory effects, and to inhibit the
      septic process in an experimental model of mice. METHODS: Three experimental
      groups (male C57BL/6 mice) were formed for the test: control group, untreated
      septic group and septic group treated with MSCs (1 * 10(6) cells/animal).
      RESULTS: In the control group, there were no deaths; in the untreated septic
      group, the mortality rate was 100 % within 26 h; in the septic group treated with
      MSCs, the mortality rate reached 40 % within 26 h. The group treated with MSCs
      was able to reduce the markers of tissue damage in the liver and pancreas. The
      treated group had a reduction of inflammatory markers. Furthermore, the MSCs
      treated group was able to inhibit the increase of apoptosis in splenocytes
      observed in the untreated septic group. CONCLUSIONS: Our data showed that MSCs
      ameliorated the immune response with decrease of inflammatory cytokines and
      increase anti-inflammatory IL-10; moreover, inhibited splenocytes apoptosis and,
      consequently, inhibited tissue damage during sepsis.

PMID- 24888324
TI  - Editorial comment: symposium: complex issues in glenohumeral instability.

PMID- 24888325
TI  - Letter to the editor: is stability of the proximal tibiofibular joint important
      in the multiligament-injured knee?

PMID- 24888323
TI  - Water-soluble phenol TS-13 combats acute but not chronic inflammation.
AB  - OBJECTIVE: This study was conducted to evaluate the effect of the synthetic water
      soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl
      thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling
      system, in experimental models of acute and chronic inflammation. METHODS: Acute
      local inflammation was induced by intraplantar carrageenan injection into rat
      hind paws, and acute systemic inflammation was modeled by intravenous zymosan
      injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic
      inflammation was investigated in rat models of air pouch and collagen-induced
      arthritis. The effects of TS-13 treatment were estimated by changes in the
      intensity of inflammation (paw edema, liver infiltration, animal survival,
      exudation, and clinical score of arthritis) and by the effects on reactive oxygen
      species (ROS) generation by leukocytes from peripheral blood and inflammatory
      exudates. RESULTS: We found the significant increase in expression of mRNA,
      content of protein and activity of a well-characterized Nrf2 target enzyme
      glutathione S-transferase P1, as well as nuclear extract protein binding to the
      ARE consensus sequence in liver of mice fed with diet containing TS-13. TS-13
      markedly attenuated carrageenan-induced paw edema, reduced blood granulocyte
      number and volume density of liver infiltrates in the systemic zymosan-induced
      inflammation model, and increased mice survival after lipopolysaccharide-induced
      septic shock. However, TS-13 administration did not influence cell and protein
      exudation into air pouches and suppressed clinical manifestation of collagen
      induced polyarthritis only at early stages. Nevertheless, TS-13 inhibited the
      generation of ROS by leukocytes in all inflammation models. CONCLUSION: The data
      suggest that the anti-inflammatory effects of Keap1/Nrf2/ARE system are more
      prominent against acute innate-mediated inflammation than chronic immune
      inflammation. This narrows the potential therapeutic efficacy of ARE inducers in
      inflammation treatment.

PMID- 24888326
TI  - Role of environmental survival in transmission of Campylobacter jejuni.
AB  - Campylobacter species are the most common cause of bacterial gastroenteritis,
      with C. jejuni responsible for the majority of these cases. Although it is clear
      that livestock, and particularly poultry, are the most common source, it is
      likely that the natural environment (soil and water) plays a key role in
      transmission, either directly to humans or indirectly via farm animals. It has
      been shown using multilocus sequence typing that some clonal complexes (such as
      ST-45) are more frequently isolated from environmental sources such as water,
      suggesting that strains vary in their ability to survive in the environment.
      Although C. jejuni are fastidious microaerophiles generally unable to grow in
      atmospheric levels of oxygen, C. jejuni can adapt to survival in the environment,
      exhibiting aerotolerance and starvation survival. Biofilm formation, the viable
      but nonculturable state, and interactions with other microorganisms can all
      contribute to survival outside the host. By exploiting high-throughput
      technologies such as genome sequencing and RNA Seq, we are well placed to
      decipher the mechanisms underlying the variations in survival between strains in
      environments such as soil and water and to better understand the role of
      environmental persistence in the transmission of C. jejuni directly or indirectly
      to humans.

PMID- 24888327
TI  - A system for automated, noninvasive, morphology-based evaluation of induced
      pluripotent stem cell cultures.
AB  - Due to the rapid adoption and use of human induced pluripotent stem cells (iPSCs)
      in recent years, there is a need for new technologies that standardize the
      evaluation of iPSCs to allow the objective comparison of results across different
      experiments and groups. In this article, we present a noninvasive, fully
      automated, and analytical system for morphology-based evaluation of iPSC cultures
      that consists of time-lapse microscopy and novel image analysis software. The
      presented system acquires low-light phase-contrast images of iPSC growth
      collected during a period of several days in culture, measures geometrical- and
      texture-based features of iPSC colonies throughout time, and derives a set of six
      biologically relevant features to automatically rank the quality of the cell
      culture. In a study of 94 iPSC cultures, we demonstrated the accuracy of the
      system by comparing the automated ranking with an independent expert evaluation
      based on visual review of the time-lapse movies. To our knowledge, this is the
      first demonstration of a fully automated and objective assessment of iPSC culture
      quality using noninvasive methods. 

PMID- 24888328
TI  - Study on the fluorescence resonance energy transfer between CdS quantum dots and
      Eosin Y.
AB  - Water-soluble CdS quantum dots (QDs) were prepared using mercaptoacetic acid
      (TGA) as the stabilizer in an aqueous system. A fluorescence resonance energy
      transfer (FRET) system was constructed between water-soluble CdS QDs (donor) and
      Eosin Y (acceptor). Several factors that impacted the fluorescence spectra of the
      FRET system, such as pH (3.05-10.10), concentration of Eosin Y (2-80 mg/L) and
      concentration of CdS QDs (2-80 mg/L), were investigated and refined. Donor-to
      acceptor ratios, the energy transfer efficiency (E) and the distance (r) between
      CdS QDs and Eosin Y were obtained. The results showed that a FRET system could be
      established between water-soluble CdS QDs and Eosin Y at pH 5.0; donor-to
      acceptor ratios demonstrated a 1: 8 proportion of complexes; the energy transfer
      efficiency (E) and the distance (r) between the QDs and Eosin Y were 20.07% and
      4.36 nm,respectively.

PMID- 24888329
TI  - Excited state kinetics of anthracene-bridge-aniline intramolecular exciplexes.
AB  - We report on the synthesis and characterization of fluorescent halogen
      substituted anthracene-bridge-aniline (ABA) supermolecules that undergo
      structural reorganization on photoexcitation to form transient complexes. The
      syntheses were achieved in high yields on a large scale and the molecular
      structures were confirmed by single crystal X-ray diffraction. The photophysics
      of the ABA supermolecules were investigated using steady state and time resolved
      optical spectroscopy. Despite the presence of heavy atoms the series of ABA
      molecules have high quantum yields of fluorescence from both a locally excited
      anthracene state (LE) and an excited state complex (exciplex, EP) in non-polar
      solvents. The kinetics of the excited state processes were established in decalin
      from the time-resolved emission, and was shown to be strongly influenced by an
      electron-transfer state (ET). For quantitative studies of the excited state
      dynamics, the presence of this state required the development of a numerical
      three-excited-state kinetic model to replace the commonly used two-excited-state
      model. The experimental results shows that the reaction rates are strongly
      influenced both by substituents and solvent, illustrating the importance of
      including all relevant states in the kinetic modeling. Ultimately it is
      established that the excited state dynamics can conveniently be followed by
      optical methods, and the applicability of the system as a model system in time
      resolved X-ray scattering experiments is discussed. 

PMID- 24888330
TI  - Effects of Echis pyramidum snake venom on hepatic and renal antioxidant enzymes
      and lipid peroxidation in rats.
AB  - The effects of Echis pyramidum venom (EPV) (0.25, 0.50, and 1.00 mg/kg) on
      activities of superoxide dismutase (SOD) and catalase (CAT) and levels of
      thiobarbituric acid reactive substances (TBARS) and total thiols (T-SH) in liver
      and kidneys of rats were investigated. EPV significantly and dose dependently
      decreased the activities of SOD and CAT in livers. Although the kidney SOD and
      CAT activities were not affected by low and medium doses of EPV, the high dose
      significantly reduced the activities of these enzymes. Liver and kidney TBARS
      levels were not affected by the low and medium doses of EPV, whereas the high
      dose significantly increased the TBARS after 6 h postdosing. There was a
      significant depletion of T-SH in liver and kidneys of rats exposed to a high dose
      of EPV. The acute phase oxidative stress due to an EPV injection points toward
      the importance of an early antioxidant therapy for the management of snake bites.

PMID- 24888332
TI  - Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield
      syndrome: a case of gonadal mosaicism.
AB  - Hartsfield syndrome has been recently reported to be associated with mutations in
      FGFR1 however, to this date; no familial cases have been reported. In this
      report, we describe two siblings with Hartsfield syndrome and a novel de novo
      FGFR1 mutation suggesting gonadal mosaicism. The proband presented at our
      institution at age 6 years with a clinical diagnosis of Hartsfield syndrome and
      requesting further genetic evaluation. Previous studies included a normal
      karyotype, oligonucleotide array, and single gene testing for nonsyndromic
      holoprosencephaly (SHH, SIX3, ZIC2, TGIF). At the age of 6 years, exome
      sequencing was performed and a de novo novel missense variant was identified in
      FGFR1 (coding for fibroblast growth factor-1) on chromosome 8p12: c.1880G>C
      (p.R627T). Subsequently, a younger sibling was born with the same phenotype
      (holoprosencephaly, ectrodactyly of bilateral hands and feet and bilateral cleft
      lip and palate). Targeted sequencing of FGFR1 revealed the identical variant that
      was previously identified in the proband. To our knowledge this observation is
      the first documentation of familial recurrence of Hartsfield syndrome. As both
      parents were negative for the sequence variant in FGFR1 gene by testing
      peripheral blood samples, this suggests gonadal mosaicism. The frequency of
      gonadal mosaicism in Hartsfield syndrome is not known however given our case,
      this possibility should be taken in to consideration for recurrence risk
      estimation in children of clinically unaffected parents.

PMID- 24888331
TI  - Single delivery of an adeno-associated viral construct to transfer the CASQ2 gene
      to knock-in mice affected by catecholaminergic polymorphic ventricular
      tachycardia is able to cure the disease from birth to advanced age.
AB  - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an inherited
      arrhythmogenic disorder characterized by sudden cardiac death in children. Drug
      therapy is still insufficient to provide full protection against cardiac arrest,
      and the use of implantable defibrillators in the pediatric population is limited
      by side effects. There is therefore a need to explore the curative potential of
      gene therapy for this disease. We investigated the efficacy and durability of
      viral gene transfer of the calsequestrin 2 (CASQ2) wild-type gene in a
      catecholaminergic polymorphic ventricular tachycardia knock-in mouse model
      carrying the CASQ2(R33Q/R33Q) (R33Q) mutation. METHODS AND RESULTS: We engineered
      an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of CASQ2 wild
      type (AAV9-CASQ2) plus the green fluorescent protein (GFP) gene to infect newborn
      R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to
      investigate the ability of the infection to prevent the disease and adult R33Q
      mice studied after 2 months to assess whether the AAV9-CASQ2 delivery could
      revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In
      both protocols, we observed the restoration of physiological expression and
      interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological
      and ultrastructural abnormalities in calcium release units present in R33Q mice;
      and the lack of life-threatening arrhythmias. CONCLUSIONS: Our data demonstrate
      that viral gene transfer of wild-type CASQ2 into the heart of R33Q mice prevents
      and reverts severe manifestations of catecholaminergic polymorphic ventricular
      tachycardia and that this curative effect lasts for 1 year after a single
      injection of the vector, thus posing the rationale for the design of a clinical
      trial.

PMID- 24888334
TI  - Imidazolium 2-substituted 4,5-dicyanoimidazolate ionic liquids: synthesis,
      crystal structures and structure-thermal property relationships.
AB  - Thirty six novel ionic liquids (ILs) with 1-butyl-3-methylimidazolium and 3
      methyl-1-octylimidazolium cations paired with 2-substitited 4,5
      dicyanoimidazolate anions (substituent at C2 = chloro, bromo, methoxy, vinyl,
      amino, methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, heptyl, octyl,
      nonyl, decyl, undecyl and phenyl) have been synthesized and characterized by
      using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)
      and single-crystal X-ray crystallography. The effects of cation and anion type
      and structure on the thermal properties of the resulting ionic liquids, including
      several room temperature ionic liquids (RTILs) are examined and discussed. ILs
      exhibited large liquid and crystallization ranges and formed glasses on cooling
      with glass transition temperatures in the range of -22 to -68  degrees C. The
      effects of alkyl substituents of the imidazolate anion reflected the
      crystallization, melting points and thermal decomposition of the ILs. The
      Coulombic packing force, van der Waals forces and size of the anions can be
      considered for altering the thermal transitions. Three crystal structures of the
      ILs were determined and the effects of changes to the cations and anions on the
      packing of the structure were investigated.

PMID- 24888333
TI  - Antimicrobial activity of metal based nanoparticles against microbes associated
      with diseases in aquaculture.
AB  - The emergence of diseases and mortalities in aquaculture and development of
      antibiotics resistance in aquatic microbes, has renewed a great interest towards
      alternative methods of prevention and control of diseases. Nanoparticles have
      enormous potential in controlling human and animal pathogens and have scope of
      application in aquaculture. The present investigation was carried out to find out
      suitable nanoparticles having antimicrobial effect against aquatic microbes.
      Different commercial as well as laboratory synthesized metal and metal oxide
      nanoparticles were screened for their antimicrobial activities against a wide
      range of bacterial and fungal agents including certain freshwater cyanobacteria.
      Among different nanoparticles, synthesized copper oxide (CuO), zinc oxide (ZnO),
      silver (Ag) and silver doped titanium dioxide (Ag-TiO2) showed broad spectrum
      antibacterial activity. On the contrary, nanoparticles like Zn and ZnO showed
      antifungal activity against fungi like Penicillium and Mucor species. Since CuO,
      ZnO and Ag nanoparticles showed higher antimicrobial activity, they may be
      explored for aquaculture use. 

PMID- 24888336
TI  - Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk
      leukemia chemotherapy.
AB  - Histiocytic sarcoma (HS) is a malignant tumor composed of proliferating cells of
      histiocytic origin. True HS is exceedingly rare, particularly in pediatric
      patients. These tumors are frequently aggressive, and outcome for patients with
      HS has traditionally been poor. There is currently no consensus on the optimal
      management of these tumors, with the literature consisting largely of case
      reports and small case series utilizing a wide variety of therapies. We describe
      a case of HS in an 8-year-old female who was successfully treated with an
      abbreviated leukemia chemotherapy regimen.

PMID- 24888335
TI  - Physical, emotional, and social health differences between posttreatment young
      adults with cancer and matched healthy controls.
AB  - BACKGROUND: Young adults (YAs; ages 18-39 years) with cancer face interrupted
      developmental milestones and increased stressors that can adversely influence
      psychosocial adjustment. Transitioning from active treatment to posttreatment
      survivorship can be particularly challenging. The purpose of this study is to
      describe the health-related quality of life (HRQL) and psychological adaptation
      of YAs after treatment, relative to young adults without cancer. METHODS: Three
      cohorts of YAs of mixed cancer diagnoses (N = 120, 0-12 months after treatment; N
      = 102, 13-24 months after treatment; and N = 113, 25-60 months after treatment;
      combined M = 31.8 years old, combined sex = 68% women) and an age-, education-,
      sex-, and partner status-matched group of healthy control participants (HCs; N =
      335) were recruited via an online research panel. All participants completed
      measures assessing demographic and clinical characteristics, HRQL (physical,
      emotional, social, and spiritual), and psychological adaptation (anxiety,
      depression, positive affect, posttraumatic growth). Measure content was slightly
      modified for applicability to HCs without a cancer history. RESULTS: Multivariate
      analysis of covariance found a significant main effect for group (YAs versus HCs)
      and a significant group-by-cohort interaction. YAs reported poorer physical (P =
      .005, d = .22) and emotional well-being (P = .011, d = .20) but better social
      well-being (P < .001, d = .49). YAs reported comparatively stable scores (P =
      .74) for posttraumatic growth compared to HCs, who reported greater posttraumatic
      growth across cohorts (P = .01, d = 16). CONCLUSIONS: Findings underscore the
      negative and positive sequelae for YAs and highlight the need for comprehensive
      assessment among YA survivors of cancer. A matched, HC group allows the HRQL and
      psychological adaptation of YAs to be placed in context, enabling a more precise
      determination of the impact of cancer on YAs.

PMID- 24888337
TI  - Reduced levels of interleukin-1 receptor antagonist act as a marker for pneumonia
      in the elderly.
AB  - Pneumonia is a disease causing serious inflammation and infection of the lungs
      and accounts for >50,000 mortalities annually. The elderly are at an increased
      risk of developing pneumonia. Pneumonia is more serious in the elderly than in
      any other age group due to the increased inflammation and risk of community
      acquired pneumonia associated with aging. Interleukin-1 receptor antagonist (IL
      1RA) is an anti-inflammatory protein that counteracts the destructive effects of
      inflammatory proteins. Therefore, the possible association between pneumonia in
      elderly individuals and reduced levels of IL-1RA was investigated in the present
      study. The number of lymphocytes was counted in all subjects and the relative
      protein expression levels of IL-1RA were determined using western blot analysis.
      In addition, the immunological activities of IL-1RA were measured using ELISA.
      The results demonstrated that the numbers of lymphocytes in the serum and
      bronchoalveolar lavage fluid (BALF) were significantly higher in elderly patients
      than those in young patients. Furthermore, the serum and BALF levels of IL-1RA in
      elderly patients were significantly lower than those in young patients (P<0.05
      and P<0.01, respectively). Therefore, reduced levels of IL-1RA in BALF may act as
      a marker for pneumonia in the elderly and may be a potential adjuvant for the
      diagnosis of pneumonia in elderly individuals. The results also showed that
      smoking was associated with significant reductions in the levels of IL-1RA in the
      BALF of elderly patients. The association between smokers and non-smokers found
      in this study provides support for the hypothesis that smoking may contribute to
      the pathogenesis of pneumonia by further reducing IL-IRA levels in certain
      elderly patients. 

PMID- 24888338
TI  - Using soluble polymers to enforce catalyst-phase-selective solubility and as
      antileaching agents to facilitate homogeneous catalysis.
AB  - The enforced phase-selective solubility of polyisobutylene (PIB)-bound Rh(II)
      catalysts in biphasic heptane/acetonitrile mixtures can be used not only to
      recycle these catalysts but also to minimize bimolecular reactions with ethyl
      diazoacetate. When cyclopropanation and O-H insertion reactions are carried out
      with PIB-bound Rh(II) catalysts either with or without addition of an
      unfunctionalized hydrocarbon polymer cosolvent, dimer by-product formation is
      suppressed even without slow syringe pump addition of the ethyl diazoacetate.
      This suppression of by-product formation is shown to be due to increased phase
      segregation of the soluble polymer-bound catalyst and the ethyl diazoacetate
      reactant. These studies also reveal that added hydrocarbon polymer cosolvents can
      function as antileaching agents, decreasing the already small amount of a soluble
      polymer-bound species that leaches into a polar phase in a biphasic mixture
      during a liquid/liquid separation step.

PMID- 24888339
TI  - New incentives are needed to boost research data sharing, says expert group.

PMID- 24888341
TI  - Primary cutaneous nodular amyloidosis associated with psoriasis.
AB  - Primary cutaneous nodular amyloidosis (PCNA) presents as solitary or multiple
      firm, waxy nodules with a predilection for acral areas. Histologically, PCNA can
      be identical to myeloma-associated systemic amyloidosis with monoclonal
      immunoglobulin light chain deposits. We describe a patient in whom PCNA developed
      in a scar in an area affected by chronic plaque psoriasis. PCNA has previously
      been associated with other autoimmune diseases, but to our knowledge, this is the
      first association with psoriasis. Interestingly, T helper (Th)17 cells, which are
      crucial in psoriasis pathogenesis, have recently been implicated in promotion of
      myeloma and plasma cell dyscrasias. The association of psoriasis and plasma-cell
      light chain production in the skin, as in this case, suggests a possible role for
      Th17 cells in PCNA formation. The dermatopathological literature of this rare but
      important disease is discussed. 

PMID- 24888340
TI  - Family predictors of continuity and change in social and physical aggression from
      ages 9 to 18.
AB  - This research examined developmental trajectories for social and physical
      aggression for a sample followed from age 9 to 18, and investigated possible
      family predictors of following different trajectory groups. Participants were 158
      girls and 138 boys, their teachers, and their parents (21% African American, 5.3%
      Asian, 51.6% Caucasian, and 21% Hispanic). Teachers rated children's social and
      physical aggression yearly in grades 3-12. Participants' parent (83% mothers)
      reported on family income, conflict strategies, and maternal authoritarian and
      permissive parenting styles. The results suggested that both social and physical
      aggression decline slightly from middle childhood through late adolescence. Using
      a dual trajectory model, group-based mixture modeling revealed three trajectory
      groups for both social and physical aggression: low-, medium-, and high-desisting
      for social aggression, and stably-low, stably-medium, and high-desisting for
      physical aggression. Membership in higher trajectory groups was predicted by
      being from a single-parent family, and having a parent high on permissiveness.
      Being male was related to both elevated physical aggression trajectories and the
      medium-desisting social aggression trajectory. Negative interparental conflict
      strategies did not predict social or physical aggression trajectories when
      permissive parenting was included in the model. Permissive parenting in middle
      childhood predicted following higher social aggression trajectories across many
      years, which suggests that parents setting fewer limits on children's behaviors
      may have lasting consequences for their peer relations. Future research should
      examine transactional relations between parenting styles and practices and
      aggression to understand the mechanisms that may contribute to changes in
      involvement in social and physical aggression across childhood and adolescence.

PMID- 24888342
TI  - Tracing the colonization and diversification of the worldwide seabird
      ectoparasite Ixodes uriae.
AB  - Historical patterns of dispersal and population isolation are key components
      shaping contemporary genetic diversity across landscapes and require explicit
      consideration when examining the relative role of different factors in driving
      the evolution of host specificity in parasitic organisms. In this study, we
      investigate the worldwide colonization history of a common ectoparasite of
      seabirds, the tick Ixodes uriae. This tick has a circumpolar distribution across
      both hemispheres but has repeatedly formed host-specific races within different
      regions. By combining mitochondrial and nuclear data, we infer how this species
      spread to its present-day distribution and how the colonization process may have
      affected the geographic and host-associated structure of this tick within
      regions. We demonstrate that I. uriae is highly structured at a global scale and
      isolates into four genetic groups that correspond to well-defined geographical
      regions. Molecular dating suggests that the diversification of I. uriae began in
      the early Miocene (22 Myr) and that this tick colonized most of the southern
      hemisphere before moving into northern latitudes via two independent routes.
      However, no relationship between the degree of host race divergence and
      colonization history was evident, supporting previous hypotheses that host
      specialization evolves relatively rapidly in this parasite, but does not
      typically lead to speciation. We discuss the possible historical and contemporary
      mechanisms of large-scale dispersal for this ectoparasite and how its biological
      characteristics may condition current patterns of genetic diversity. More
      generally, our results illustrate how combining broad-scale sampling and modern
      molecular tools can help disentangle complex patterns of diversification in
      widespread parasites.

PMID- 24888343
TI  - Comparison of rankings for lean meat based on results from a CT scanner and a
      video image analysis system.
AB  - Coopworth cross lambs born over three years were examined in this study.
      Differences between two machines; a computer tomography (CT) scanner and a
      VIAScan(r) system for the estimation of carcase lean weight in lamb carcases was
      examined. The CT scanner provided a significantly higher estimate of carcase
      lean. The rank correlation (0.84) between the CT scanner and the VIAScan(r)
      system for the prediction of carcase lean was significant, but there was a
      different ranking for carcase lean depending on which machine was used. This has
      important ramifications for the use of VIAScan(r) data in the New Zealand Sheep
      Improvement Ltd genetic programme. 

PMID- 24888344
TI  - Critical considerations on the utility of FDG-PET/CT for posttreatment restaging
      of the bone marrow in diffuse large B-cell lymphoma.

PMID- 24888345
TI  - Sequence selective capture, release and analysis of DNA using a magnetic
      microbead-assisted toehold-mediated DNA strand displacement reaction.
AB  - This paper reports on the modification of magnetic beads with oligonucleotide
      capture probes with a specially designed pendant toehold (overhang) aimed
      specifically to capture double-stranded PCR products. After capture, the PCR
      products were selectively released from the magnetic beads by means of a toehold
      mediated strand displacement reaction using short artificial oligonucleotide
      triggers and analysed using capillary electrophoresis. The approach was
      successfully shown on two genes widely used in human DNA genotyping, namely human
      c-fms (macrophage colony-stimulating factor) proto-oncogene for the CSF-1
      receptor (CSF1PO) and amelogenin. 

PMID- 24888346
TI  - Halogen- and hydrogen-bonding catenanes for halide-anion recognition.
AB  - Halogen-bonding (XB) interactions were exploited in the solution-phase assembly
      of anion-templated pseudorotaxanes between an isophthalamide-containing
      macrocycle and bromo- or iodo-functionalised pyridinium threading components.
      (1)H NMR spectroscopic titration investigations demonstrated that such XB
      interpenetrated assemblies are more stable than analogous hydrogen bonding (HB)
      pseudorotaxanes. The stability of the anion-templated halogen-bonded
      pseudorotaxane architectures was exploited in the preparation of new halogen
      bonding interlocked catenane species through a Grubbs' ring-closing metathesis
      (RCM) clipping methodology. The catenanes' anion recognition properties in the
      competitive CDCl(3)/CD(3) OD 1:1 solvent mixture revealed selectivity for the
      heavier halides iodide and bromide over chloride and acetate.

PMID- 24888347
TI  - Fatty acid synthesis and lipid metabolism in the obligate biotrophic fungus
      Rhizophagus irregularis during mycorrhization of Lotus japonicus.
AB  - Arbuscular mycorrhiza formation with fungi of the Glomeromycota represents a
      widespread symbiotic interaction of vascular plants. Different signaling events
      and metabolic adaptations are required for the close interaction between the two
      partners. Membrane lipid synthesis is a prerequisite for symbiosis, and membrane
      properties depend on lipid composition. Lipid profiling was performed by liquid
      chromatography mass spectrometry to study the role of triacylglycerol,
      diacylglycerol, phospholipids, galactolipids, sterols and sphingolipids during
      the colonization of Lotus japonicus roots with Rhizophagus irregularis (syn.
      Glomus intraradices). Mycorrhization leads to an increased phosphate supply and
      suppresses the increase in galactolipids commonly observed in phosphate-deprived
      plants. In addition to free sterols and sterol esters, R. irregularis contains
      sterol glucosides and acylated sterol glucosides. Glycosylated sphingolipids
      (glucosylceramide, dihexosylceramide) and inositolphosphorylceramide were
      detected in the fungus. Lyso-phosphatidylcholine, a lipid previously implicated
      in mycorrhiza signaling, is present in low amounts in mock-infected and
      mycorrhized roots. The composition of fungal phospholipids changes after
      mycorrhization because molecular species with palmitvaccenic (di-16:1) or
      tetracosenoic (24:1) acyl groups decrease in intraradical mycelium. This
      adaptation of lipid metabolism during intraradical growth is likely a
      prerequisite for symbiosis, achieving functional compatibility between the fungal
      and the periarbuscular membrane. Data mining in genomic and transcript databases
      revealed the presence of genes encoding enzymes of lipid biosynthesis in R.
      irregularis. However, no gene encoding multidomain fatty acid de novo synthase
      was detected in the genome sequence of this obligate biotrophic fungus.

PMID- 24888349
TI  - Chip-based capillary electrophoresis profiling of olive pollen extracts used for
      allergy diagnosis and immunotherapy.
AB  - Standardization of protein extracts for clinical purposes represents an important
      task in order to maintain adequate reactivity, presence of the relevant
      allergens, and safety among other factors. The main objective of this work was to
      explore the potential use of a chip-based automated CE system commercially
      available to analyze several of the most common forms of allergenic extracts from
      olive pollen used in allergy clinics. These include experimental extracts
      prepared from olive pollens, in-house reference extracts, extracts designed for
      skin prick test assays, and a panel of vaccine variants aimed to specific
      immunotherapy. As a major conclusion of the study, chip-based CE allowed in all
      cases to determine accurate protein profiles with different degrees of
      sensitivity, where several allergens (particularly the major olive pollen
      allergen Ole e 1) were easily recognized. Moreover, several purified allergens
      were also analyzed by this method, and proposed as specific standards for
      different purposes. In the present condition, the method can only provide the
      protein profile of the extracts with respect to a preestablished standard
      extract, but not allergen identification. However, these and other future
      developments and applications are discussed.

PMID- 24888350
TI  - The effect of tendon vibration on motor unit activity, intermuscular coherence
      and force steadiness in the elbow flexors of males and females.
AB  - BACKGROUND: Compartmentalized responses in motor unit (MU) activity of the short
      head (SH) and long head (LH) of the biceps brachii are observed following forearm
      position change. Differential muscle spindle afferent distribution has been
      proposed as a potential mechanism underlying this behaviour. Tendon vibration is
      an effective, non-invasive method of increasing muscle spindle afferent activity
      of a target muscle group offering a paradigm in which this hypothesis may be
      investigated further. AIM: To determine the effect of tendon vibration on MU
      recruitment and discharge rates of the SH and LH, muscle activity of the elbow
      flexors and triceps brachii, intermuscular coherence among the SH, LH,
      brachioradialis and triceps brachii and force steadiness in young males and
      females during isometric elbow flexion. METHODS: Intramuscular electromyography
      (EMG) of the SH and LH, and surface EMG of the elbow flexors were recorded pre-
      and post-vibration during low-force isometric contractions. Motor unit
      recruitment thresholds, MU discharge rates and MU discharge variability; surface
      EMG amplitude, intermuscular coherence and force steadiness were determined pre-
      and post-vibration. RESULTS: Differential changes in all MU properties, EMG
      amplitude and intermuscular coherence were observed among elbow flexors. Although
      MU properties exhibited differential changes, they accounted for little variance
      in isometric force steadiness. However, intermuscular EMG coherence among all
      muscles investigated was reduced post-vibration. CONCLUSION: Uncoupling of common
      oscillatory input as a result of differential muscle spindle afferent inputs to
      elbow flexors may be responsible for the reduction in force steadiness following
      tendon vibration and a forearm position change.

PMID- 24888348
TI  - Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from
      the human microbiome.
AB  - Pyridoxal-5'-phosphate or PLP, the active form of vitamin B6, is a highly
      versatile cofactor that participates in a large number of mechanistically diverse
      enzymatic reactions in basic metabolism. PLP-dependent enzymes account for ~1.5%
      of most prokaryotic genomes and are estimated to be involved in ~4% of all
      catalytic reactions, making this an important class of enzymes. Here, we
      structurally and functionally characterize three novel PLP-dependent enzymes from
      bacteria in the human microbiome: two are from Eubacterium rectale, a dominant,
      nonpathogenic, fecal, Gram-positive bacteria, and the third is from Porphyromonas
      gingivalis, which plays a major role in human periodontal disease. All adopt the
      Type I PLP-dependent enzyme fold and structure-guided biochemical analysis
      enabled functional assignments as tryptophan, aromatic, and probable
      phosphoserine aminotransferases. 

PMID- 24888352
TI  - Can a white nurse get it? 'Reflexive practice' and the non-Indigenous
      clinician/researcher working with Aboriginal people.
AB  - CONTEXT: Reflexivity is crucial for non-Aboriginal researchers working with
      Aboriginal people. This article describes a process of 'reflexive practice'
      undertaken by a white clinician/researcher while working with Aboriginal people.
      The clinician/researcher elicited Aboriginal people's experience of being
      haemodialysis recipients in rural Australia and their perceptions of their
      disease and treatment. The aim of this article is to report the methods used
      during this qualitative project to guide the researcher in conducting culturally
      appropriate health research with Aboriginal people. The goal of this work was to
      improve health services, informed and guided by the Aboriginal recipients
      themselves. The article describes the theory and methods used to develop
      reflexive skills. It also reports how the clinician/researcher managed her
      closeness to the topic and participants (some being patients under her care) and
      the processes used to ensure her subjectivity did not interfere with the quality
      of research. ISSUES: Three layers of reflexive practice are described: examining
      self within the research, examining interpersonal relationships with
      participants, and examining health systems. The alignment of the three 'lenses'
      used to describe the study is exposed. Complex insider/outsider roles are
      explored through multiple layers of reflexive practice. Regular journal writing
      was the primary tool used to undertake this reflexive practice. An Aboriginal
      advisory group and co-investigators collaborated and assisted the
      clinician/researcher to scrutinise and understand her positioning within the
      study. Researcher positioning, power and unequal relationships are discussed.
      Issues such as victim blaming and the disconnect between clinicians' views about
      treatment compliance and Aboriginal peoples' prioritisation of family obligations
      for before treatment are presented. LESSONS LEARNED: Aboriginal patients must
      negotiate a health services system where racism and victim blaming are
      institutionalised, but the effect of these on the research relationship can be
      mitigated through reflexive practice. Using a framework for relational
      accountability that incorporates respect, responsibility and reciprocity can
      enable non-Aboriginal clinicians and/or researchers to work effectively with
      Aboriginal patients. These results may assist clinicians and policy makers
      develop strategies for improving quality of care.

PMID- 24888353
TI  - Institutional capacity for health systems research in East and Central Africa
      schools of public health: enhancing capacity to design and implement teaching
      programs.
AB  - BACKGROUND: The role of health systems research (HSR) in informing and guiding
      national programs and policies has been increasingly recognized. Yet, many
      universities in sub-Saharan African countries have relatively limited capacity to
      teach HSR. Seven schools of public health (SPHs) in East and Central Africa
      undertook an HSR institutional capacity assessment, which included a review of
      current HSR teaching programs. This study determines the extent to which SPHs are
      engaged in teaching HSR-relevant courses and assessing their capacities to
      effectively design and implement HSR curricula whose graduates are equipped to
      address HSR needs while helping to strengthen public health policy. METHODS: This
      study used a cross-sectional study design employing both quantitative and
      qualitative approaches. An organizational profile tool was administered to senior
      staff across the seven SPHs to assess existing teaching programs. A self
      assessment tool included nine questions relevant to teaching capacity for HSR
      curricula. The analysis triangulates the data, with reflections on the responses
      from within and across the seven SPHs. Proportions and average of values from the
      Likert scale are compared to determine strengths and weaknesses, while themes
      relevant to the objectives are identified and clustered to elicit in-depth
      interpretation. RESULTS: None of the SPHs offer an HSR-specific degree program;
      however, all seven offer courses in the Master of Public Health (MPH) degree that
      are relevant to HSR. The general MPH curricula partially embrace principles of
      competency-based education. Different strengths in curricula design and staff
      interest in HSR at each SPH were exhibited but a number of common constraints
      were identified, including out-of-date curricula, face-to-face delivery
      approaches, inadequate staff competencies, and limited access to materials.
      Opportunities to align health system priorities to teaching programs include
      existing networks. CONCLUSIONS: Each SPH has key strengths that can be leveraged
      to design and implement HSR teaching curricula. We propose networking for
      standardizing HSR curricula competencies, institutionalizing sharing of teaching
      resources, creating an HSR eLearning platform to expand access, regularly
      reviewing HSR teaching content to infuse competency-based approaches, and
      strengthening staff capacity to deliver such curricula.

PMID- 24888351
TI  - Dopamine D4 receptors inhibit proliferation and migration of vascular smooth
      muscle cells induced by insulin via down-regulation of insulin receptor
      expression.
AB  - Vascular smooth muscle cells (VSMCs) proliferation and migration, which are
      central in the development of vascular diseases, are regulated by numerous
      hormones and humoral factors. Activation of the insulin receptor stimulates VSMCs
      proliferation while dopamine receptors, via D1 and D3 receptors, inhibit the
      stimulatory effects of norepinephrine on VSMCs proliferation. We hypothesize that
      activation of the D4 dopamine receptor may also inhibit the proliferation and
      migration of VSMCs, therefore, inhibit atherosclerosis. Our current study found
      that insulin increased the proliferation and migration of A10 cells, an effect
      that was reduced in the presence of a D4 receptor agonist, PD168077. The negative
      effect of the D4 receptor on insulin's action may be via decreasing insulin
      receptor expression, because activation of the D4 receptor inhibited insulin
      receptor protein and mRNA expressions, indicating that the regulation occured at
      the transcriptional or post-transcriptional levels. To determine whether or not
      the inhibition of D4 receptor on insulin-mediated proliferation and migration of
      VSMCs has physiological significance, hyper-insulinemic Sprague-Dawley rats with
      balloon-injured carotid artery were treated with a D4 agonist, PD168077, (6
      mg/kg/d) for 14 days. We found that PD168077 significantly inhibited neointimal
      formation by inhibition of VSMC proliferation. This study suggests that
      activation of the D4 receptor suppresses the proliferation and migration of
      VSMCs, therefore, inhibit atherosclerosis. The D4 receptor may be a potential
      therapeutic target to reduce the effects of insulin on artery remodeling.

PMID- 24888354
TI  - Direct observation of genomic heterogeneity through local haplotyping analysis.
AB  - BACKGROUND: It has been an abiding belief among geneticists that multicellular
      organisms' genomes can be analyzed under the assumption that a single individual
      has a uniform genome in all its cells. Despite some evidence to the contrary,
      this belief has been used as an axiomatic assumption in most genome analysis
      software packages. In this paper we present observations in human whole genome
      data, human whole exome data and in mouse whole genome data to challenge this
      assumption. We show that heterogeneity is in fact ubiquitous and readily
      observable in ordinary Next Generation Sequencing (NGS) data. RESULTS: Starting
      with the assumption that a single NGS read (or read pair) must come from one
      haplotype, we built a procedure for directly observing haplotypes at a local
      level by examining 2 or 3 adjacent single nucleotide polymorphisms (SNPs) which
      are close enough on the genome to be spanned by individual reads. We applied this
      procedure to NGS data from three different sources: whole genome of a Central
      European trio from the 1000 genomes project, whole genome data from laboratory
      bred strains of mouse, and whole exome data from a set of patients of head and
      neck tumors. Thousands of loci were found in each genome where reads spanning 2
      or 3 SNPs displayed more than two haplotypes, indicating that the locus is
      heterogeneous. We show that such loci are ubiquitous in the genome and cannot be
      explained by segmental duplications. We explain them on the basis of cellular
      heterogeneity at the genomic level. Such heterogeneous loci were found in all
      normal and tumor genomes examined. CONCLUSIONS: Our results highlight the need
      for new methods to analyze genomic variation because existing ones do not
      systematically consider local haplotypes. Identification of cancer somatic
      mutations is complicated because of tumor heterogeneity. It is further
      complicated if, as we show, normal tissues are also heterogeneous. Methods for
      biomarker discovery must consider contextual haplotype information rather than
      just whether a variant "is present".

PMID- 24888357
TI  - Ferromagnetism in the Kondo-lattice compound CePd2P2.
AB  - We report physical properties of CePd2P2 crystallizing in the tetragonal ThCr2Si2
      type structure (space group I4/mmm). Dc-magnetic susceptibility, magnetization,
      specific heat, electrical resistivity and magnetoresistance measurements
      establish a ferromagnetic ordering below the Curie temperature TC = 28.4 +/- 0.2
      K. Critical analysis of isothermal and isofield magnetization yields critical
      exponents of beta = 0.405 +/- 0.005, gamma = 1.11 +/- 0.05 and delta = 3.74 +/-
      0.04. The ordered state is characterized by saturation moment Ms ~ 0.98MUB and
      magnon energy gap Delta/kB ~25-35 K. The studied properties reflect a competing
      influence of the Kondo and crystalline electric field (CEF) interactions. The
      strength of the Kondo effect is assigned by a low-temperature Kondo scale TK ~19
      +/- 10 K and a high-temperature Kondo scale TK ~ H 117 ?} 10 K. A model of the
      inelastic scattering of the conduction electrons with an exchanged CEF energy
      DeltaCEF was applied to the magnetic resistivity. An average value DeltaCEF = 260
      +/- 30 K is consistent in the relationships with TK and TK H. We argue that the
      CePd2P2 compound appears to be a new ferromagnetic Kondo-lattice among the Ce
      based intermetallics.

PMID- 24888356
TI  - Incorporating external evidence in trial-based cost-effectiveness analyses: the
      use of resampling methods.
AB  - BACKGROUND: Cost-effectiveness analyses (CEAs) that use patient-specific data
      from a randomized controlled trial (RCT) are popular, yet such CEAs are
      criticized because they neglect to incorporate evidence external to the trial. A
      popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap.
      The objective of the present study was to further expand the bootstrap method of
      RCT-based CEA for the incorporation of external evidence. METHODS: We utilize the
      Bayesian interpretation of the bootstrap and derive the distribution for the cost
      and effectiveness outcomes after observing the current RCT data and the external
      evidence. We propose simple modifications of the bootstrap for sampling from such
      posterior distributions. RESULTS: In a proof-of-concept case study, we use data
      from a clinical trial and incorporate external evidence on the effect size of
      treatments to illustrate the method in action. Compared to the parametric models
      of evidence synthesis, the proposed approach requires fewer distributional
      assumptions, does not require explicit modeling of the relation between external
      evidence and outcomes of interest, and is generally easier to implement. A
      drawback of this approach is potential computational inefficiency compared to the
      parametric Bayesian methods. CONCLUSIONS: The bootstrap method of RCT-based CEA
      can be extended to incorporate external evidence, while preserving its appealing
      features such as no requirement for parametric modeling of cost and effectiveness
      outcomes.

PMID- 24888358
TI  - Spontaneous dimer states of the Abeta(21-30) decapeptide.
AB  - Constant temperature and replica-exchange molecular dynamics simulations of two
      Abeta21-30 decapeptides in explicit solvent reveal metastable dimer states that
      are abundant near physiological temperatures. As Alzheimer's disease is
      associated with the neurotoxic oligomers of amyloid beta-protein, the formation
      of these dimers provides insight into oligomer assembly. 

PMID- 24888355
TI  - Cardiovascular medication utilization and adherence among adults living in rural
      and urban areas: a systematic review and meta-analysis.
AB  - BACKGROUND: Rural residents face numerous barriers to healthcare access and
      studies suggest poorer health outcomes for rural patients. Therefore we undertook
      a systematic review to determine if cardiovascular medication utilization and
      adherence patterns differ for rural versus urban patients. METHODS: A
      comprehensive search of major electronic datasets was undertaken for controlled
      clinical trials and observational studies comparing utilization or adherence to
      cardiovascular medications in rural versus urban adults with cardiovascular
      disease or diabetes. Two reviewers independently identified citations, extracted
      data, and evaluated quality using the STROBE checklist. Risk estimates were
      abstracted and pooled where appropriate using random effects models. Methods and
      reporting were in accordance with MOOSE guidelines. RESULTS: Fifty-one studies
      were included of fair to good quality (median STROBE score 17.5). Although pooled
      unadjusted analyses suggested that patients in rural areas were less likely to
      receive evidence-based cardiovascular medications (23 studies, OR 0.88, 95% CI
      0.79, 0.98), pooled data from 21 studies adjusted for potential confounders
      indicated no rural-urban differences (adjusted OR 1.02, 95% CI 0.91, 1.13). The
      high heterogeneity observed (I(2) = 97%) was partially explained by treatment
      setting (hospital, ambulatory care, or community-based sample), age, and disease.
      Adherence did not differ between urban versus rural patients (3 studies, OR 0.94,
      95% CI 0.39, 2.27, I(2) = 91%). CONCLUSIONS: We found no consistent differences
      in rates of cardiovascular medication utilization or adherence among adults with
      cardiovascular disease or diabetes living in rural versus urban settings. Higher
      quality evidence is needed to determine if differences truly exist between urban
      and rural patients in the use of, and adherence to, evidence-based medications.

PMID- 24888359
TI  - Recombinant form of mammalian gp91(phox) is active in the absence of p22(phox).
AB  - The flavocytochrome b558 of the phagocyte NADPH oxidase complex comprises two
      membrane proteins, a glycosylated gp91phox and a non-glycosylated p22phox.
      Gp91phox contains all of the redox carriers necessary to reduce molecular oxygen
      to superoxide using NADPH. The capacity of gp91phox to produce superoxide in the
      absence of its membrane partner p22phox has been little studied. In the present
      study, we have generated in Pichia pastoris for the first time an active form of
      bovine gp91phox able to carry out the entire NADPH oxidase activity in the
      absence of p22phox. Collected information on the maturation and the activity of
      the recombinant gp91phox and the participation of individual cytosolic subunits
      in the active complex allowed us to propose, in the absence of p22phox, an
      unconventional stabilized complex compared with the heterodimer. 

PMID- 24888360
TI  - Current approaches of the management of mercury poisoning: need of the hour.
AB  - Mercury poisoning cases have been reported in many parts of the world, resulting
      in many deaths every year. Mercury compounds are classified in different chemical
      types such as elemental, inorganic and organic forms. Long term exposure to
      mercury compounds from different sources e.g. water, food, soil and air lead to
      toxic effects on cardiovascular, pulmonary, urinary, gastrointestinal,
      neurological systems and skin. Mercury level can be measured in plasma, urine,
      feces and hair samples. Urinary concentration is a good indicator of poisoning of
      elemental and inorganic mercury, but organic mercury (e.g. methyl mercury) can be
      detected easily in feces. Gold nanoparticles (AuNPs) are a rapid, cheap and
      sensitive method for detection of thymine bound mercuric ions. Silver
      nanoparticles are used as a sensitive detector of low concentration Hg2+ ions in
      homogeneous aqueous solutions. Besides supportive therapy, British anti lewisite,
      dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA. succimer) and
      dimercaptopropanesulfoxid acid (DMPS) are currently used as chelating agents in
      mercury poisoning. Natural biologic scavengers such as algae, azolla and other
      aquatic plants possess the ability to uptake mercury traces from the environment.

PMID- 24888362
TI  - Apolipoprotein E4 carrier status plus circulating anti-NMDAR1 autoantibodies:
      association with schizoaffective disorder.

PMID- 24888361
TI  - Elevated fetal steroidogenic activity in autism.
AB  - Autism affects males more than females, giving rise to the idea that the
      influence of steroid hormones on early fetal brain development may be one
      important early biological risk factor. Utilizing the Danish Historic Birth
      Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid
      samples of males born between 1993 and 1999 who later received ICD-10
      (International Classification of Diseases, 10th Revision) diagnoses of autism,
      Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise
      specified) (n=128) compared with matched typically developing controls.
      Concentration levels of Delta4 sex steroids (progesterone, 17alpha-hydroxy
      progesterone, androstenedione and testosterone) and cortisol were measured with
      liquid chromatography tandem mass spectrometry. All hormones were positively
      associated with each other and principal component analysis confirmed that one
      generalized latent steroidogenic factor was driving much of the variation in the
      data. The autism group showed elevations across all hormones on this latent
      generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation
      was uniform across ICD-10 diagnostic label. These results provide the first
      direct evidence of elevated fetal steroidogenic activity in autism. Such
      elevations may be important as epigenetic fetal programming mechanisms and may
      interact with other important pathophysiological factors in autism. 

PMID- 24888364
TI  - Identification of increased genetic risk scores for schizophrenia in treatment
      resistant patients.

PMID- 24888366
TI  - How dimensionality changes the anomalous behavior and melting scenario of a core
      softened potential system?
AB  - We present a computer simulation study of the phase diagram and anomalous
      behavior of two-dimensional (2D) and three-dimensional (3D) classical particles
      repelling each other through an isotropic core-softened potential. As in the
      analogous three-dimensional case, in 2D a reentrant-melting transition occurs
      upon compression under not too high pressure, along with a spectrum of
      thermodynamic and dynamic anomalies in the fluid phase. However, in two
      dimensions the order of the region of anomalous diffusion and the region of
      structural anomaly is inverted in comparison with the 3D case, where there exists
      a water-like sequence of anomalies, and has a silica-like sequence. In the low
      density part of the 2D phase diagram, melting is a continuous two-stage
      transition, with an intermediate hexatic phase. All available evidence supports
      the Kosterlitz-Thouless-Halperin-Nelson-Young (KTHNY) scenario for this melting
      transition. On the other hand, at high density part of the phase diagram one
      first-order transition takes place. 

PMID- 24888365
TI  - A retrospective analysis of the clinical efficacies of Q-switched Alexandrite and
      Q-switched Nd:YAG lasers in the treatment of nevus of Ota in Korean patients.
AB  - BACKGROUND: While the Q-switched Alexandrite laser (QSAL) and the Q-switched
      neodymium: yttrium-aluminum-garnet (QSNY) laser have been widely used in treating
      nevus of Ota, few studies compared them. OBJECTIVE: To compare the efficacies of
      the QSAL and the QSNY laser in the treatment of nevus of Ota in Korean patients.
      METHODS AND MATERIALS: A retrospective multicenter study was conducted in 76
      patients with nevus of Ota. Thirty-one patients were treated with a QSAL (5.5-8.0
      J/cm(2), 4-mm spot size) and 45 patients were treated with QSNY laser (6.0-12.0
      J/cm(2), 2-mm spot size). Treatment outcomes were categorized into five grades
      and the results were compared with the relevant variables taken into account
      using multivariate logistic regression analysis. RESULTS: QSAL treatment was more
      likely to achieve a better response compared with that with QSNY laser treatment.
      The odds ratio of achieving an excellent response, compared with the odds ratio
      of having a poor response, was 12.213-times more likely when a QSAL was used than
      when a QSNY laser was used (p = 0.026). CONCLUSION: The QSAL tends to be more
      efficient than the QSNY laser in the treatment of nevus of Ota in Korean
      patients. Further controlled, prospective comparison studies are needed.

PMID- 24888363
TI  - MIR137 variants identified in psychiatric patients affect synaptogenesis and
      neuronal transmission gene sets.
AB  - Sequence analysis of 13 microRNA (miRNA) genes expressed in the human brain and
      located in genomic regions associated with schizophrenia and/or bipolar disorder,
      in a northern Swedish patient/control population, resulted in the discovery of
      two functional variants in the MIR137 gene. On the basis of their location and
      the allele frequency differences between patients and controls, we explored the
      hypothesis that the discovered variants impact the expression of the mature miRNA
      and consequently influence global mRNA expression affecting normal brain
      functioning. Using neuronal-like SH-SY5Y cells, we demonstrated significantly
      reduced mature miR-137 levels in the cells expressing the variant miRNA gene.
      Subsequent transcriptome analysis showed that the reduction in miR-137 expression
      led to the deregulation of gene sets involved in synaptogenesis and neuronal
      transmission, all implicated in psychiatric disorders. Our functional findings
      add to the growing data, which implicate that miR-137 has an important role in
      the etiology of psychiatric disorders and emphasizes its involvement in nervous
      system development and proper synaptic function. 

PMID- 24888367
TI  - New insight into the spin-conserving excitation of the negatively charged
      nitrogen-vacancy center in diamond.
AB  - The negatively charged nitrogen-vacancy (N-V(-)) color center in diamond is an
      important solid-state single photon source for applications to quantum
      communication and distributed quantum computation. Its full usefulness relies on
      sufficient radiative emission of the optical photons which requires realizable
      control to enhance emission into the zero-phonon line (ZPL) but until now is
      still a challenge. Detailed understanding of the associated excitation process
      would be of essential importance for such objective. Here we report a theoretical
      work that probes the spin-conserving optical excitation of the N-V(-) center.
      Using density-functional-theory (DFT) calculations, we find that the ZPL and the
      phonon-side band (PSB) depend sensitively on the axial strain of the system.
      Besides, we find a relatively small PSB appearing at about 100 GPa in the
      emission spectrum at low temperatures, which provides a means to enhance the
      coherent emission of the N-V(-) center in quantum optical networks. 

PMID- 24888368
TI  - Osmotic stress decreases aquaporin-4 expression in the human retinal pigment
      epithelial cell line, ARPE-19.
AB  - The regulation of water movement is of utmost importance for normal retinal
      function. Under physiological conditions, water is transported, dependent on the
      osmotic gradient, through the retinal pigment epithelial cell layer from the
      subretinal space to the choroid. The osmotic gradient has been found to be
      modified in eye diseases, thus leading to water accumulation in the subretinal
      space and the sensory retina, and subsequently contributing to the formation of
      macular oedema. Understanding the regulation of aquaporin expression is therefore
      crucial. In this study, we investigated the effects of hyperosmolarity on
      aquaporin-4 (AQP4) protein expression in the human retinal pigment epithelial
      cell line, ARPE-19. AQP4 expression was examined by PCR, western blot analysis
      and immunofluorescence. Ubiquitinylation was examined by immunoprecipitation. The
      results revealed that hyperosmotic stress rapidly decreased AQP4 expression in
      the ARPE-19 cells. The effect remained unmodified by lysosomal or mitogen
      activated protein kinase inhibitors, but was reversed by proteasome inhibitors.
      However, no ubiquitinylation of AQP4 was detected. Our results suggest that
      hyperosmotic stress markedly reduces AQP4 expression possibly through a
      proteasome ubiquitinylation-independent pathway. This may represent an adaptation
      to hyperosmotic stress. The results presented in this study contribute to our
      understanding of the formation of macular oedema.

PMID- 24888369
TI  - Nuclear factor-kappaB is involved in the protocadherin-10-mediated pro-apoptotic
      effect in multiple myeloma.
AB  - The gene encoding protocadherin-10 (PCDH10), a member of the cadherin
      superfamily, has been recently identified as a tumor suppressor gene (TSG).
      PCDH10 plays important roles in the apoptosis of tumor cells in some cancer
      types. However, the exact role of PCDH10 in multiple myeloma (MM) is largely
      unknown. Increasing evidence has suggested that the activation of nuclear factor
      kappaB (NF-kappaB) is crucial for apoptosis in myeloma cells. In this study, we
      investigated the pro-apoptotic effect of PCDH10 on myeloma cells and whether this
      effect may involve inhibition of the NF-kappaB pathway. We report here, for the
      first time to the best of our knowledge, that PCDH10 markedly induces apoptosis
      of myeloma cells, accompanied by an increase in activated caspase-3 and poly-ADP
      ribose polymerase (PARP) levels, and inhibited expression of anti-apoptotic
      proteins. We also demonstrate that PCDH10 inhibits the activation of NF-kappaB,
      by inhibiting the expression of the inhibitor of nuclear factor-kappaB (IkappaB)
      kinase subunits (IKKs) and the phosphorylation of IkappaBalpha. Moreover, the
      constitutive NF-kappaB DNA-binding activity and the expression of the NF-kappaB
      regulated proteins cyclooxygenase-2 (COX-2), vascular endothelial growth factor
      (VEGF) and intercellular adhesion molecule 1 (ICAM-1) were inhibited by PCDH10 in
      MM cells. These results suggest that PCDH10 induces myeloma cell apoptosis,
      probably by inhibiting the NF-kappaB pathway. 

PMID- 24888370
TI  - The counterfeit anti-malarial is a crime against humanity: a systematic review of
      the scientific evidence.
AB  - BACKGROUND: The counterfeiting of anti-malarials represents a form of attack on
      global public health in which fake and substandard anti-malarials serve as de
      facto weapons of mass destruction, particularly in resource-constrained endemic
      settings, where malaria causes nearly 660,000 preventable deaths and threatens
      millions of lives annually. It has been estimated that fake anti-malarials
      contribute to nearly 450,000 preventable deaths every year. This crime against
      humanity is often underestimated or ignored. This study attempts to describe and
      characterize the direct and indirect effects of counterfeit anti-malarials on
      public health, clinical care and socio-economic conditions. METHODS: A search was
      performed using key databases, WHO documents, and English language search
      engines. Of 262 potential articles that were identified using a fixed set of
      criteria, a convenience sample of 105 appropriate articles was selected for this
      review. RESULTS: Artemisinin-based combination therapy (ACT) is an important tool
      in the fight against malaria, but a sizable number of patients are unable to
      afford to this first-line treatment. Consequently, patients tend to procure
      cheaper anti-malarials, which may be fake or substandard. Forensic palynology
      reveals that counterfeits originate in Asia. Fragile drug regulations,
      ineffective law-enforcement agencies and corruption further burden ailing
      healthcare facilities. Substandard/fake anti-malarials can cause (a) economic
      sabotage; (b) therapeutic failure; (c) increased risk of the emergence and spread
      of resistant strains of Plasmodium falciparum and Plasmodium vivax; (d) an
      undermining of trust/confidence in healthcare stakeholders/systems; and, (e)
      serious side effects or death. CONCLUSION: Combating counterfeit anti-malarials
      is a complex task due to limited resources and poor techniques for the detection
      and identification of fake anti-malarials. This situation calls for sustainable,
      global, scientific research and policy change. Further, responsible stakeholders
      in combination with the synthesis and supply of next generation malaria control
      tools, such as low-cost anti-malarials, must promote the development of a
      counterfeit-free and malaria-free future.

PMID- 24888371
TI  - Institutional capacity for health systems research in East and Central African
      Schools of Public Health: strengthening human and financial resources.
AB  - BACKGROUND: Despite its importance in providing evidence for health-related
      policy and decision-making, an insufficient amount of health systems research
      (HSR) is conducted in low-income countries (LICs). Schools of public health
      (SPHs) are key stakeholders in HSR. This paper, one in a series of four, examines
      human and financial resources capacities, policies and organizational support for
      HSR in seven Africa Hub SPHs in East and Central Africa. METHODS: Capacity
      assessment done included document analysis to establish staff numbers,
      qualifications and publications; self-assessment using a tool developed to
      capture individual perceptions on the capacity for HSR and institutional
      dialogues. Key informant interviews (KIIs) were held with Deans from each SPH and
      Ministry of Health and non-governmental officials, focusing on perceptions on
      capacity of SPHs to engage in HSR, access to funding, and organizational support
      for HSR. RESULTS: A total of 123 people participated in the self-assessment and
      73 KIIs were conducted. Except for the National University of Rwanda and the
      University of Nairobi SPH, most respondents expressed confidence in the adequacy
      of staffing levels and HSR-related skills at their SPH. However, most of the
      researchers operate at individual level with low outputs. The average number of
      HSR-related publications was only <1 to 3 per staff member over a 6-year period
      with most of the publications in international journals. There is dependency on
      external funding for HSR, except for Rwanda, where there was little government
      funding. We also found that officials from the Ministries of Health often
      formulate policy based on data generated through ad hoc technical reviews and
      consultancies, despite their questionable quality. CONCLUSIONS: There exists
      adequate skilled staff for HSR in the SPHs. However, HSR conducted by
      individuals, fuelled by Ministries' of Health tendency to engage individual
      researchers, undermines institutional capacity. This study underscores the need
      to form effective multidisciplinary teams to enhance research of immediate and
      local relevance. Capacity strengthening in the SPH needs to focus on knowledge
      translation and communication of findings to relevant audiences. Advocacy is
      needed to influence respective governments to allocate adequate funding for HSR
      to avoid donor dependency that distorts local research agenda.

PMID- 24888373
TI  - PEGylation of ORMOSIL nanoparticles differently modulates the in vitro toxicity
      toward human lung cells.
AB  - ORganically MOdified SILica (ORMOSIL) nanoparticles (NPs) appear promising
      carriers for the delivery of drugs to target tissues but concerns on possible
      cytotoxic effects exist. Here, we studied the in vitro responses to ORMOSIL NPs
      in different types of human lung cells to determine the effects of polyethylene
      glycol (PEG) coating on NP cytotoxicity. Non-PEG NPs caused a concentration
      dependent decrease of viability of all types of cells, while PEG NPs induced
      deleterious effects and death in carcinoma alveolar type II A549 cells but not in
      CCD-34Lu fibroblasts and NCI-H2347 adenocarcinoma cells. Reactive oxygen species
      were detected in cells incubated with PEG NPs, but their deactivation by
      superoxide dismutase and catalase did not protect A549 cells from death,
      suggesting that the oxidative stress was not the main determinant of
      cytotoxicity. Only in A549 cells PEG NPs modulated the transcription of genes
      involved in inflammation, signal transduction and cell death. Transmission
      electron microscopy evidenced a unique intracellular localization of PEG NPs in
      the lamellar bodies of A549 cells, which could be the most relevant factor
      leading to cytotoxicity by reducing the production of surfactant proteins and by
      interfering with the pulmonary surfactant system.

PMID- 24888372
TI  - Use of cortical stimulation in neuropathic pain, tinnitus, depression, and
      movement disorders.
AB  - Medical treatment must strike a balance between benefit and risk. As the field of
      neuromodulation develops, decreased invasiveness, in combination with maintenance
      of efficacy, has become a goal. We provide a review of the history of cortical
      stimulation from its origins to the current state. The first part discusses
      neuropathic pain and the nonpharmacological treatment options used. The second
      part covers transitions to tinnitus, believed by many to be another
      deafferentation disorder, its classification, and treatment. The third part
      focuses on major depression. The fourth section concludes with the discussion of
      the use of cortical stimulation in movement disorders. Each part discusses the
      development of the field, describes the current care protocols, and suggests
      future avenues for research needed to advance neuromodulation. 

PMID- 24888375
TI  - Proposal of an in silico profiler for categorisation of repeat dose toxicity data
      of hair dyes.
AB  - This study outlines the analysis of 94 chemicals with repeat dose toxicity data
      taken from Scientific Committee on Consumer Safety opinions for commonly used
      hair dyes in the European Union. Structural similarity was applied to group these
      chemicals into categories. Subsequent mechanistic analysis suggested that
      toxicity to mitochondria is potentially a key driver of repeat dose toxicity for
      chemicals within each of the categories. The mechanistic hypothesis allowed for
      an in silico profiler consisting of four mechanism-based structural alerts to be
      proposed. These structural alerts related to a number of important chemical
      classes such as quinones, anthraquinones, substituted nitrobenzenes and aromatic
      azos. This in silico profiler is intended for grouping chemicals into mechanism
      based categories within the adverse outcome pathway paradigm.

PMID- 24888374
TI  - EGFR mediates docetaxel resistance in human castration-resistant prostate cancer
      through the Akt-dependent expression of ABCB1 (MDR1).
AB  - Recent studies have shown that docetaxel-based chemotherapy confers a survival
      benefit in patients with castration-resistant prostate cancer (PC). Also
      epidermal growth factor receptor (EGFR) was found to have multiple roles in
      prostatic tumorigenesis. However, the EGFR-mediated chemoresistance mechanism in
      human PC was not well delineated. In this study, we explored the mechanism of
      EGFR-mediated docetaxel resistance in PC. A series of stable docetaxel-resistant
      PC/DX sublines were established at our laboratory. The docetaxel IC50s of PC3 and
      PC/DX25 cells were 0.01 and 1.33 MUM, respectively. Cellular resistance to
      docetaxel was significantly associated with increased EGFR and EGFR activation in
      PC/DX25. There was a dose-dependent increase in EGFR expression associated with
      the magnitude of docetaxel resistance. Expression of EGFR in PC/DX25 was higher
      than that in PC3, RWPE-1 and LNCaP cells. Similar results were also found in
      human PC tissues by immunohistochemical staining. We showed that docetaxel
      sensitivity can be stored in PC/DX25 cells by knockdown and inactivation of EGFR
      expression through EGFR siRNA and specific inhibitors, respectively. Contrarily,
      overexpression of EGFR or recombinant EGF protein treatment could rescue PC3
      cells from docetaxel-mediated cytotoxicity. Gefitninb (ZD1839) significantly
      inhibited the growth of PC/DX25 cells by MTT in vitro and on xenografted nude
      mice in vivo. Moreover, EGFR-mediated docetaxel resistance occurred through the
      Akt-dependent ABCB1 expression in PC cells. These findings demonstrated EGFR
      played an important role in docetaxel-resistant PC and EGFR inhibition may
      enhance the therapeutic efficacy of docetaxel-based treatment.

PMID- 24888376
TI  - The feed contaminant deoxynivalenol affects the intestinal barrier permeability
      through inhibition of protein synthesis.
AB  - Deoxynivalenol (DON) has critical health effects if the contaminated grains
      consumed by humans or animals. DON can have negative effects on the active
      transport of glucose and amino acids in the small intestine of chickens. As the
      underlying mechanisms are not fully elucidated, the present study was performed
      to delineate more precisely the effects of cycloheximide (protein synthesis
      inhibitor, CHX) and DON on the intestinal absorption of nutrients. This was to
      confirm whether DON effects on nutrient absorption are due to an inhibition of
      protein synthesis. Changes in ion transport and barrier function were assessed by
      short-circuit current (Isc) and transepithelial ion conductance (Gt) in Ussing
      chambers. Addition of D-glucose or L-glutamine to the luminal side of the
      isolated mucosa of the jejunum increased (P < 0.001) the Isc compared with basal
      conditions in the control tissues. However, the Isc was not increased by the
      glucose or glutamine addition after pre-incubation of tissues with DON or CHX.
      Furthermore, both DON and CHX reduced Gt, indicating that the intestinal barrier
      is compromised and consequently induced a greater impairment of the barrier
      function. The remarkable similarity between the activity of CHX and DON on
      nutrient uptake is consistent with their common ability to inhibit protein
      synthesis. It can be concluded that the decreases in transport activity by CHX
      was evident in this study using the chicken as experimental model. Similarly, DON
      has negative effects on the active transport of some nutrients, and these can be
      explained by its influence on protein synthesis.

PMID- 24888379
TI  - Persistent non-metallic behavior in Sr2IrO4 and Sr3Ir2O7 at high pressures.
AB  - Iridium-based 5d transition-metal oxides are attractive candidates for the study
      of correlated electronic states due to the interplay of enhanced crystal-field,
      Coulomb and spin-orbit interaction energies. At ambient pressure, these
      conditions promote a novel Jeff = 1/2 Mott-insulating state, characterized by a
      gap of the order of ~0.1 eV. We present high-pressure electrical resistivity
      measurements of single crystals of Sr2IrO4 and Sr3Ir2O7. While no indications of
      a pressure-induced metallic state up to 55 GPa were found in Sr2IrO4, a strong
      decrease of the gap energy and of the resistance of Sr3Ir2O7 between ambient
      pressure and 104 GPa confirm that this compound is in the proximity of a metal
      insulator transition.

PMID- 24888378
TI  - Comparison of RNA-Seq by poly (A) capture, ribosomal RNA depletion, and DNA
      microarray for expression profiling.
AB  - BACKGROUND: RNA sequencing (RNA-Seq) is often used for transcriptome profiling as
      well as the identification of novel transcripts and alternative splicing events.
      Typically, RNA-Seq libraries are prepared from total RNA using poly(A) enrichment
      of the mRNA (mRNA-Seq) to remove ribosomal RNA (rRNA), however, this method fails
      to capture non-poly(A) transcripts or partially degraded mRNAs. Hence, a mRNA-Seq
      protocol will not be compatible for use with RNAs coming from Formalin-Fixed and
      Paraffin-Embedded (FFPE) samples. RESULTS: To address the desire to perform RNA
      Seq on FFPE materials, we evaluated two different library preparation protocols
      that could be compatible for use with small RNA fragments. We obtained paired
      Fresh Frozen (FF) and FFPE RNAs from multiple tumors and subjected these to
      different gene expression profiling methods. We tested 11 human breast tumor
      samples using: (a) FF RNAs by microarray, mRNA-Seq, Ribo-Zero-Seq and DSN-Seq
      (Duplex-Specific Nuclease) and (b) FFPE RNAs by Ribo-Zero-Seq and DSN-Seq. We
      also performed these different RNA-Seq protocols using 10 TCGA tumors as a
      validation set.The data from paired RNA samples showed high concordance in
      transcript quantification across all protocols and between FF and FFPE RNAs. In
      both FF and FFPE, Ribo-Zero-Seq removed rRNA with comparable efficiency as mRNA
      Seq, and it provided an equivalent or less biased coverage on gene 3' ends.
      Compared to mRNA-Seq where 69% of bases were mapped to the transcriptome, DSN-Seq
      and Ribo-Zero-Seq contained significantly fewer reads mapping to the
      transcriptome (20-30%); in these RNA-Seq protocols, many if not most reads mapped
      to intronic regions. Approximately 14 million reads in mRNA-Seq and 45-65 million
      reads in Ribo-Zero-Seq or DSN-Seq were required to achieve the same gene
      detection levels as a standard Agilent DNA microarray. CONCLUSIONS: Our results
      demonstrate that compared to mRNA-Seq and microarrays, Ribo-Zero-Seq provides
      equivalent rRNA removal efficiency, coverage uniformity, genome-based mapped
      reads, and consistently high quality quantification of transcripts. Moreover,
      Ribo-Zero-Seq and DSN-Seq have consistent transcript quantification using FFPE
      RNAs, suggesting that RNA-Seq can be used with FFPE-derived RNAs for gene
      expression profiling.

PMID- 24888377
TI  - Mechanistic relationships between hepatic genotoxicity and carcinogenicity in
      male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures.
AB  - The genotoxicity of a complex mixture [neutral fraction (NF)] from a wood
      preserving waste and reconstituted mixture (RM) mimicking the NF with seven major
      polycyclic aromatic hydrocarbons (PAHs) and benzo(a)pyrene (BaP) was investigated
      by determining DNA adducts and tumor incidence in male B6C3F1 mice exposed to
      three different doses of the chemical mixtures. The peak values of DNA adducts
      were observed after 24 h, and the highest levels of PAH-DNA adducts were
      exhibited in mice administered NF + BaP, and the highest tumor incidence and
      mortality were also observed in this group. DNA adduct levels after 1, 7, or 21
      days were significantly correlated with animal mortality and incidence of total
      tumors including liver, lung, and forestomach. However, only hepatic DNA adducts
      after 7 days significantly correlated with liver tumor incidence. Most proteins
      involved in DNA repair including ATM, pATR, Chk1, pChk1, DNA PKcs, XRCC1, FANCD2,
      Ku80, Mre11, and Brca2 were significantly lower in liver tumor tissue compared to
      non-tumor tissue. Expressions of proteins involved in apoptosis and cell cycle
      regulation were also significantly different in tumor versus non-tumor tissues,
      and it is possible that PAH-induced changes in these gene products are important
      for tumor development and growth.

PMID- 24888380
TI  - An overview of home tonometry and telemetry for intraocular pressure monitoring
      in humans.
AB  - PURPOSE: To review the existing technology for self-tonometry and evaluate
      methods for continuous monitoring of IOP currently undergoing development and
      clinical trials in humans. BACKGROUND: Glaucoma is one of the leading causes of
      blindness worldwide. Current glaucoma therapy is focused primarily on lowering
      intraocular pressures (IOP). Decisions to modify treatment regiments are
      primarily based on office IOP. Since IOP fluctuates throughout the day, values
      obtained in the office may be a poor representation of the patient's disease. IOP
      measurements outside of the physician's office environment would provide better
      knowledge of the disease state and allow for better-informed medical decision
      making. METHODS AND RESULTS: We performed a literature search using Medline and
      IEEE database for studies investigating technologies that have been developed for
      continuous 24-hour IOP monitoring. CONCLUSION: There is currently no technology
      that has been approved for use to allow for continuous monitoring of IOP
      fluctuations. New experimental technology being developed and currently
      undergoing clinical trials has demonstrated potential for changing the diagnosis
      and management of glaucoma.

PMID- 24888382
TI  - The Allergic Airway Inflammation Repository--a user-friendly, curated resource of
      mRNA expression levels in studies of allergic airways.
AB  - Public microarray databases allow analysis of expression levels of candidate
      genes in different contexts. However, finding relevant microarray data is
      complicated by the large number of available studies. We have compiled a user
      friendly, open-access database of mRNA microarray experiments relevant to
      allergic airway inflammation, the Allergic Airway Inflammation Repository (AAIR,
      http://aair.cimed.ike.liu.se/). The aim is to allow allergy researchers to
      determine the expression profile of their genes of interest in multiple clinical
      data sets and several experimental systems quickly and intuitively. AAIR also
      provides quick links to other relevant information such as experimental
      protocols, related literature and raw data files. 

PMID- 24888381
TI  - Toward onset prevention of cognitive decline in adults with Down syndrome (the
      TOP-COG study): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Early-onset dementia is common in Down syndrome adults, who have
      trisomy 21. The amyloid precursor protein gene is on chromosome 21, and so is
      over-expressed in Down syndrome, leading to amyloid beta (Abeta) over-production,
      a major upstream pathway leading to Alzheimer disease (AD). Statins (microsomal 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), have pleiotropic
      effects including potentially increasing brain amyloid clearance, making them
      plausible agents to reduce AD risk. Animal models, human observational studies,
      and small scale trials support this rationale, however, there are no AD primary
      prevention trials in Down syndrome adults. In this study we study aim to inform
      the design of a full-scale primary prevention trial. METHODS/DESIGN: TOP-COG is a
      feasibility and pilot double-blind randomized controlled trial (RCT), with a
      nested qualitative study, conducted in the general community. About 60 Down
      syndrome adults, aged >=50 will be included. The intervention is oral simvastatin
      40 mg at night for 12 months, versus placebo. The primary endpoint is recruitment
      and retention rates. Secondary endpoints are (1) tolerability and safety; (2)
      detection of the most sensitive neurocognitive instruments; (3) perceptions of
      Down syndrome adults and caregivers on whether to participate, and assessment
      experiences; (4) distributions of cognitive decline, adaptive behavior, general
      health/quality of life, service use, caregiver strain, and sample size
      implications; (5) whether Abeta42/Abeta40 is a cognitive decline biomarker. We
      will describe percentages recruited from each source, the number of contacts to
      achieve this, plus recruitment rate by general population size. We will calculate
      summary statistics with 90% confidence limits where appropriate, for each study
      outcome as a whole, by treatment group and in relation to baseline age, cognitive
      function, cholesterol and other characteristics. Changes over time will be
      summarized graphically. The sample size for a definitive RCT will be estimated
      under alternative assumptions. DISCUSSION: This study is important, as AD is a
      major problem for Down syndrome adults, for whom there are currently no effective
      preventions or treatments. It will also delineate the most suitable assessment
      instruments for this population. Recruitment of intellectually disabled adults is
      notoriously difficult, and we shall provide valuable information on this,
      informing future studies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN
      Register ID: ISRCTN67338640 (17 November 2011).

PMID- 24888383
TI  - Does B-type natriuretic peptide-guided therapy improve outcomes in patients with
      chronic heart failure? A systematic review and meta-analysis of randomized
      controlled trials.
AB  - The role of B-type natriuretic peptide (BNP) in the management of patients with
      chronic heart failure (CHF) was uncertain. The aim of this meta-analysis was to
      comprehensively evaluate the effect of BNP-guided therapy in CHF. Relevant
      randomized controlled trials were identified by searching of Pubmed, Embase and
      the Cochrane Library databases. Fixed or randomized effect models were applied to
      combine the data according to the heterogeneity of the included studies. Fourteen
      studies with 3,004 CHF patients were included. Results of our meta-analyses
      suggested that compared with clinical group, BNP-guided treatment significantly
      decreased the risk of heart failure-related hospitalization (RR 0.79, 95 % CI
      0.63-0.98, p = 0.03), although did not significantly affect the risk of all-cause
      mortality (RR 0.94, 95 % CI 0.81-1.08, p = 0.39) or all-cause hospitalization (RR
      0.97, 95 % CI 0.89-1.07, p = 0.56). Furthermore, between-group BNP changes seemed
      to be a significant modifier to the effects of BNP-guided therapy on clinical
      outcomes, and BNP-guided therapy may improve the clinical outcomes of CHF
      patients if substantial reduction of BNP can be achieved. In addition, BNP-guided
      therapy was not associated with increased risk for serious adverse events. BNP
      guided therapy may improve the clinical outcomes of CHF patients if substantial
      reduction of BNP can be achieved. BNP-guided therapy seemed to be safe and
      promising for CHF patients, and future studies with well-designed BNP-guided
      medication up-titration strategies are needed to confirm these results.

PMID- 24888385
TI  - The expanding horizon of immunotherapy in the treatment of malignant disorders:
      allogeneic hematopoietic stem cell transplantation and beyond.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a very effective
      therapeutic modality with curative potential in patients with hematological
      malignancies. The therapeutic efficacy is mainly based on the alloreactive
      reaction of donor lymphocytes against malignant cells of the recipient named as
      'graft-versus-leukemia' or 'graft-versus-tumor' (GVL, GVT) effect. However,
      besides the beneficial GVL effect, alloreactive reaction attacks normal cells and
      provokes the deleterious 'graft-versus-host disease' (GVHD) which represents the
      major limitation of allo-SCT. Current trials have focused on a dual goal:
      augmentation of GVL and complete abolishment of GVHD. From a theoretical point of
      view complete dissociation of GVL from GVHD can occur by selecting antigenic
      targets present on malignant and absent from normal cells. Hematopoietic tissue
      restricted minor histocompatibility antigens and leukemia or tumor-associated
      antigens are ideal candidates for tumor-targeted immunotherapy. Other options for
      inducing anti-tumor immunity in the absence of GVHD are natural killer (NK) cell
      immunotherapy, amplification of immune responses by using monoclonal antibodies,
      and bispecific T and NK-cell engagers. Genetically modified immune effectors such
      as T-cells armed with chimeric antigen receptors (CAR) or transduced with T-cell
      receptors with anti-tumor specificity are another exciting field of immunotherapy
      against malignancies.

PMID- 24888384
TI  - A new common mutation in the cardiac beta-myosin heavy chain gene in Finnish
      patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: In the nationwide FinHCM Study including 306 Finnish patients with
      hypertrophic cardiomyopathy (HCM), we have previously identified two founder
      mutations in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C
      (MYBPC3-Q1061X) genes, accounting for 18% of all cases. Objective. To screen
      additional mutations, previously identified in eastern Finnish cohorts with HCM,
      in the FinHCM Study population. PATIENTS AND METHODS: Ten mutations in the beta
      myosin heavy chain gene (MYH7), TPM1, and MYBPC3 were screened. RESULTS: MYH7
      R1053Q was found in 17 of 306 patients (5.6%). No carriers of MYH7-R719W or N696S
      were found. A novel TPM1-D175G mutation was found in a single patient. MYBPC3
      mutations were found in 14 patients: IVS5-2A-C in two, IVS14-13G-A in two,
      K811del in six, and A851insT in four patients. Altogether, a HCM-causing mutation
      was identified in 32 patients, accounting for 10.5% of all cases. In addition,
      two MYBPC3 variants R326Q and V896M with uncertain pathogenicity were found in
      eight and in 10 patients, respectively. CONCLUSION: Combining the present
      findings with our previous results, a causative mutation was identified in 28% of
      the FinHCM cohort. MYH7-R1053Q was the third most common mutation, and should be
      screened in all new cases of HCM in Finland.

PMID- 24888386
TI  - Direct oral anticoagulants as alternative treatment options for the effective
      long-term treatment of patients with pulmonary embolism in primary care: a
      review.
AB  - Pulmonary embolism (PE) represents a potentially life-threatening venous
      thromboembolic disorder, and prompt treatment is vital to prevent early
      mortality. However, diagnosis of PE is complicated by the range of signs and
      symptoms with which it presents. Clinical risk scores, imaging techniques, and
      laboratory tests are recommended in clinical guidelines to aid diagnosis, and
      risk stratification strategies can be used to inform treatment decisions. Long
      term anticoagulation is key to avoid the risk of later complications of acute PE,
      such as recurrent venous thromboembolism and chronic thromboembolic pulmonary
      hypertension. Rivaroxaban is a direct oral anticoagulant that has been approved
      for the treatment of PE (and deep vein thrombosis) and prevention of recurrent
      venous thromboembolism; other direct oral anticoagulants have undergone phase III
      trials for these indications. These agents may provide advantages over
      traditional anticoagulants, such as vitamin K antagonists, because they are
      administered at fixed doses and do not require routine coagulation monitoring.
      These advantages may improve patient adherence and aid general practitioners by
      simplifying long-term management of PE in daily primary care.

PMID- 24888388
TI  - Brown adipose tissue during puberty and with aging.
AB  - It was previously assumed that brown adipose tissue (BAT) is present in humans
      only for a short period following birth, the time in which mechanisms of
      generating heat by way of shivering are not yet developed. Although BAT is
      maximally recruited in early infancy, findings in recent years have led to a new
      consensus that metabolically active BAT remains present in most children and many
      adult humans. Evidence to date supports a slow and steady decline in BAT activity
      throughout life, with the exception of an intriguing spike in the prevalence and
      volume of BAT around the time of puberty that remains poorly understood. Because
      BAT activity is more commonly observed in individuals with a lower body mass
      index, an association seen in both adult and pediatric populations, there is the
      exciting possibility that BAT is protective against childhood and adult obesity.
      Indeed, the function and metabolic relevance of human BAT is currently an area of
      vigorous research. The goal of this review is to summarize what is currently
      known about changes that occur in BAT during various stages of life, with a
      particular emphasis on puberty and aging. 

PMID- 24888389
TI  - Salicylhydroxamic acid (SHAM) negatively mediates tea herbivore-induced direct
      and indirect defense against the tea geometrid Ectropis obliqua.
AB  - We investigated the effect of the SHAM treatment of tea plants on their induced
      defense on a tea geometrid (TG), Ectropis obliqua Prout. Treatment of tea leaves
      with SHAM reduced the performance of TG and TG-elicited level of the lipoxygenase
      gene CsiLOX1 and the putative allene oxide synthase gene CsiAOS1. The release of
      wound-induced green leaf volatiles (GLVs) and the expression of the hydroperoxide
      lyase (HPL) gene CsiHPL1 were also reduced by SHAM treatment. The negative effect
      of SHAM dramatically reduced the total hebivore-induced plant volatiles (HIPVs)
      and the attractiveness to the parasitoid wasp Apanteles sp. These results
      indicated that SHAM may negatively mediate tea defense response against TG by
      modulating the wound-induced emission of GLVs, the expression of genes involved
      in oxylipin pathway, and the emission of other HIPV compounds that mediate direct
      and indirect defenses.

PMID- 24888390
TI  - Endothelial cell loss and refractive predictability in femtosecond laser-assisted
      cataract surgery compared with conventional cataract surgery.
AB  - PURPOSE: To investigate the amount of endothelial cell loss (ECL) and refractive
      predictability by femtosecond laser-assisted cataract surgery (FLACS) compared to
      conventional phacoemulsification cataract surgery (CPS). METHODS: Forty-seven
      patients had one eye operated by FLACS and the contralateral eye operated by CPS
      (stop and chop technique). Both eyes had intraocular aspheric lenses implanted.
      Uncorrected distance visual acuity (UDVA), corrected distance visual acuity
      (CDVA), central corneal endothelial cell count and hexagonality with a non
      contact specular microscope were assessed preoperatively, 1-3 days
      postoperatively and 3 months postoperatively. RESULTS: Three days
      postoperatively, mean ECL was 249 cells/mm(2) (SD +/- 744) (9.1%) by FLACS and
      235 cells/mm(2) (SD +/- 681) (8.2%) by CPS (p = 0.87). Three months
      postoperatively, mean ECL was 274 cells/mm(2) (SD +/- 358) (11.4%) by FLACS
      compared with 333 cells/mm(2) (SD +/- 422) (13.9%) by CPS, (p = 0.30) 3 months
      postoperatively, hexagonality was decreased by 1.8% (SD +/- 30) by FLACS and by
      1.4% (SD +/- 13) by CPS, (p = 0.84). The mean absolute difference from the
      attempted refraction was 0.37 dioptres (D) (SD +/- 0.33) by FLACS and 0.41 D (SD
      +/- 0.42) by CPS (p = 0.56). Mean CDVA was 0.89 (0.3; 1.25) by FLACS and 0.93
      (0.4; 1.25) by CPS at 3 months postoperatively (p = 0.36). Within both groups,
      70% gained a CDVA of 6/6. Mean surgery time was 9.3 min (SD +/- 1.9) by FLACS and
      8.0 min (SD +/- 1.9) by CPS, (p = 0.0018). Mean phaco energy was 3.78 U/S (SD +/-
      5.1) and 5.45 U/S (SD +/- 4.6) (p < 0.0001) by FLACS and CPS, respectively.
      CONCLUSION: We found no significant difference in ECL and refractive
      predictability between FLACS and CPS 3 months postoperatively.

PMID- 24888387
TI  - Inherited bone marrow failure syndromes in adolescents and young adults.
AB  - The inherited bone marrow failure syndromes are a diverse group of genetic
      diseases associated with inadequate production of one or more blood cell
      lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond
      Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital
      neutropenia, and Shwachman-Diamond syndrome. The management of these disorders
      was once the exclusive domain of pediatric subspecialists, but increasingly
      physicians who care for adults are being called upon to diagnose or treat these
      conditions. Through a series of patient vignettes, we highlight the clinical
      manifestations of inherited bone marrow failure syndromes in adolescents and
      young adults. The diagnostic and therapeutic challenges posed by these diseases
      are discussed.

PMID- 24888392
TI  - Filament theory based WORM memory devices using aluminum/poly(9
      vinylcarbazole)/aluminum structures.
AB  - Spin coated poly(N-vinylcarbazole) (PVK) sandwiched between thermally evaporated
      aluminum (Al) electrodes on a glass substrate showed unipolar Write Once Read
      Many times (WORM) characteristics. The pristine devices were in the low
      resistance ON state exhibiting ohmic behavior and at a voltage near -2 V, they
      switched abruptly to the high resistance OFF state showing space charge limited
      current (SCLC). We suggest that the rupturing of metallic filaments due to Joule
      heating may explain the effect. The WORM devices exhibited an ON/OFF ratio of
      10(8), a retention of 1000 s and an endurance of ~10(6) cycles in both ON and OFF
      states. 

PMID- 24888391
TI  - Evidence for low high-density lipoprotein cholesterol levels in Australian
      indigenous peoples: a systematic review.
AB  - BACKGROUND: Low plasma high-density lipoprotein cholesterol (HDL-C) levels are a
      strong, independent, but poorly understood risk factor for cardiovascular disease
      (CVD). Although this atherogenic lipid abnormality has been widely reported in
      Australia's Indigenous peoples, Aboriginal and Torres Strait Islanders, the
      evidence has not come under systematic review. This review therefore examines
      published data for Indigenous Australians reporting 1) mean HDL-C levels for both
      sexes and 2) factors associated with low HDL-C. METHODS: PubMed, Medline and
      Informit ATSI Health databases were systematically searched between 1950 and 2012
      for studies on Indigenous Australians reporting mean HDL-C levels in both sexes.
      Retrieved studies were evaluated by standard criteria. Low HDL-C was defined as:
      <1.0 mmol/L. Analyses of primary data associating measures of HDL-C with other
      CVD risk factors were also performed. RESULTS: Fifteen of 93 retrieved studies
      were identified for inclusion. These provided 58 mean HDL-C levels; 29 for each
      sex, most obtained in rural/regional (20%) or remote settings (60%) and including
      51-1641 participants. For Australian Aborigines, mean HDL-C values ranged between
      0.81-1.50 mmol/L in females and 0.76-1.60 mmol/L in males. Two of 15 studies
      reported HDL-C levels for Torres Strait Islander populations, mean HDL-C: 1.00 or
      1.11 mmol/L for females and 1.01 or 1.13 mmol/L for males. Low HDL-C was observed
      only in rural/regional and remote settings--not in national or urban studies (n =
      3) in either gender. Diabetes prevalence, mean/median waist-to-hip ratio and
      circulating C-reactive protein levels were negatively associated with HDL-C
      levels (all P < 0.05). Thirty-four per cent of studies reported lower mean HDL-C
      levels in females than in males. CONCLUSIONS: Very low mean HDL-C levels are
      common in Australian Indigenous populations living in rural and remote
      communities. Inverse associations between HDL-C and central obesity, diabetes
      prevalence and inflammatory markers suggest a particularly adverse CVD risk
      factor profile. An absence of sex dichotomy in HDL-C levels warrants further
      investigation.

PMID- 24888394
TI  - Correlation between the human fecal microbiota and depression.
AB  - BACKGROUND: Depression is a chronic syndrome with a pathogenesis linked to
      various genetic, biological, and environmental factors. Several links between gut
      microbiota and depression have been established in animal models. In humans,
      however, few correlations have yet been demonstrated. The aim of our work was
      therefore to identify potential correlations between human fecal microbiota (as a
      proxy for gut microbiota) and depression. METHODS: We analyzed fecal samples from
      55 people, 37 patients, and 18 non-depressed controls. Our analyses were based on
      data generated by Illumina deep sequencing of 16S rRNA gene amplicons. KEY
      RESULTS: We found several correlations between depression and fecal microbiota.
      The correlations, however, showed opposite directions even for closely related
      Operational Taxonomic Units (OTU's), but were still associated with certain
      higher order phylogroups. The order Bacteroidales showed an overrepresentation (p
      = 0.05), while the family Lachnospiraceae showed an underrepresentation (p =
      0.02) of OTU's associated with depression. At low taxonomic levels, there was one
      clade consisting of five OTU's within the genus Oscillibacter, and one clade
      within Alistipes (consisting of four OTU's) that showed a significant association
      with depression (p = 0.03 and 0.01, respectively). CONCLUSIONS & INFERENCES: The
      Oscillibacter type strain has valeric acid as its main metabolic end product, a
      homolog of neurotransmitter GABA, while Alistipes has previously been shown to be
      associated with induced stress in mice. In conclusion, the taxonomic correlations
      detected here may therefore correspond to mechanistic models.

PMID- 24888393
TI  - Significant elevations of serum lipase not caused by pancreatitis: a systematic
      review.
AB  - BACKGROUND: Many authors advocate lipase as the preferred serological test for
      the diagnosis of pancreatitis and a cut-off level of three or more times the
      upper limit of normal (ULN) is often quoted. The literature contains no
      systematic review that explores alternative causes of a lipase level over three
      times as high as the ULN. Such a review was therefore the objective of this
      study. METHODS: The EMBASE and MEDLINE databases (1985 to August 2013) were
      searched for all eligible articles. Predetermined data were extracted and
      independently analysed by two reviewers. RESULTS: In total, data from 58 studies
      were included in the final analysis. The following causes other than pancreatitis
      of lipase levels exceeding three times the ULN were found: reduced clearance of
      lipase caused by renal impairment or macrolipase formation; other hepatobiliary,
      gastroduodenal, intestinal and neoplastic causes; critical illness, including
      neurosurgical pathology; alternative pancreatic diagnoses, such as non
      pathological pancreatic hyperenzymaemia, and miscellaneous causes such as
      diabetes, drugs and infections. CONCLUSIONS: A series of differential diagnoses
      for significant serum lipase elevations (i.e. exceeding three times the ULN) has
      been provided by this study. Clinicians should utilize this knowledge in the
      interpretation and management of patients who have lipase levels over three times
      as high as the ULN, remaining vigilant for an alternative diagnosis to
      pancreatitis. The medical officer should be aware of the possibility of incorrect
      diagnosis in the asymptomatic patient.

PMID- 24888395
TI  - Optimization of modified Middlebrook 7H11 agar for isolation of Mycobacterium
      bovis from raw milk cheese.
AB  - Reports have highlighted the absence of contemporary peer reviewed publications
      pertaining to Mycobacterium bovis culture from raw milk and cheese. By
      replicating traditional methods, cheese-making methodology and equipment were
      devised to produce Cheddar (n = 6) and Caerphilly (n = 3) artificially
      contaminated with M. bovis (three genotypes) under stringent laboratory
      containment guidelines for handling hazardous microbiological material.
      Middlebrook 7H11, modified for M. bovis isolation, was assessed for capacity to
      enumerate M. bovis despite changing cheese microflora and prolonged M. bovis
      exposure to the cheese matrix using maturing cheese test portions (n = 63; up to
      16 weeks). Malachite green (MG) containing media isolated M. bovis at
      significantly (P < 0.05) lower levels than unmodified Middlebrook 7H11 agar
      despite MG being a common adjunct of Middlebrook 7H11 agar modified for M. bovis
      growth. Subsequently, a selective MG-free Middlebrook 7H11 agar modified using
      haemolysed red cells and calf serum was demonstrated as the best performing (P <
      0.05) medium for recovery of M. bovis from typical UK cheese types, Cheddar and
      Caerphilly. Significance and impact of the study: Following increased M. bovis
      infection of UK cattle, the risk posed to consumers from consumption of
      unpasteurized milk and dairy products has changed. Furthermore, published methods
      for the culture and molecular detection of M. bovis in raw milk products are
      limited. Cheese-making protocols and M. bovis culture media reported here provide
      tools for further investigation of M. bovis survival during all stages of cheese
      manufacture and could inform future assessment of the risk to consumers from M.
      bovis contamination of unpasteurized dairy products.

PMID- 24888397
TI  - Latent tuberculosis infection: is universal screening the right approach?

PMID- 24888396
TI  - Improvement in in vitro fertilization rate, decrease in reactive oxygen species
      and spermatozoa death incidence in rams by dietary fish oil.
AB  - Our aim was to evaluate the effects of fish oil feeding on sperm classical
      parameters, level of reactive oxygen spices (ROS), spermatozoa death incidence
      and in vitro fertilization (IVF) rate in rams. We randomly assigned nine rams,
      into two experimental groups (isoenergetic and isonitrogenous rations with
      constant level of vitamin E supplement): control (CTR; n = 5) and fish oil (FO; n
      = 4, 35 g/day/ram). Diets were fed for 70 days during the physiological breeding
      season. After a 21-day dietary adaptation period, semen was collected weekly from
      each ram by an artificial vagina. Sperm classical parameters were determined by
      the computer-assisted sperm analyzer system (CASA), and it was prepared for IVF
      process by swim-up technique. These evaluations were performed during the first
      and last weeks of sampling. Intracellular ROS level and spermatozoa death
      incidence were detected by flow cytometry on a weekly basis after adaptation.
      Data were analysed with SPSS 15. The volume, concentration (3.6 and 2.7 * 10(9)
      /ml) and sperm progressive motility (60 and 48%) were significantly improved in
      the FO group compared with the CTR (p < 0.05). A comparison of two-cell stage
      embryos following IVF in the two groups showed a significantly higher
      fertilization rate in the FO group (56%) compared with the CTR (49%). Superoxide
      anion (O2 (-) ) rate was significantly lower (p < 0.05) at the third week of
      sampling in the FO. Although the H2 O2 rate was numerically lower in the FO group
      compared with the CTR, this difference was not significant. In addition,
      apoptosis showed a significant difference in the third week of sampling (15 and
      30% for FO and CTR, respectively; p < 0.05). Overall, adding fish oil to the ram
      diet not only improved sperm quality and IVF results, it also could reduce oxygen
      free radicals and the incidence of spermatozoa death.

PMID- 24888398
TI  - Effects of renal sympathetic denervation on the atrial electrophysiology in dogs
      with pacing-induced heart failure.
AB  - BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are associated with
      sympathetic activation. Renal sympathetic denervation (RSD) can suppress AF
      vulnerability. The impact of RSD on atrial electrophysiology in experimental HF
      is unclear. METHODS: Twenty-two beagles were randomized into control, HF, and HF
      + RSD groups. Control dogs were implanted cardiac pacemakers without pacing. Dogs
      in the HF group underwent right ventricular pacing for 3 weeks at 240 beats/min
      to induce HF. The dogs in the HF + RSD group received RSD and underwent the same
      HF-inducing procedure. RESULTS: The P-wave dispersion was higher in HF dogs than
      in the control and HF + RSD dogs (19 +/- 3.1 ms vs 13 +/- 2.3 ms, 15 +/- 2.9 ms,
      P = 0.04). Conduction time within the interatrium was significantly longer in the
      HF dogs than that in the control and HF + RSD dogs (39 +/- 4 ms vs 31 +/- 3 ms,
      33 +/- 4 ms; P = 0.03). Window of vulnerability (WOV) of AF was widened in the HF
      dogs than in the HF + RSD dogs (37 +/- 5 ms vs 14 +/- 3 ms; P < 0.01), while AF
      could not be induced (WOV = 0) in the control dogs during S1 S2 stimulation. The
      voltage in the threshold for AF inducibility was lower during ganglionated plexi
      stimulation in the HF dogs than in the control and HF + RSD dogs (1.8 +/- 0.6 V
      vs 2.5 +/- 0.6 V, 2.4 +/- 0.4 V; P = 0.04). CONCLUSIONS: RSD could reverse the
      atrial electrical remodeling and decrease AF inducibility in dogs with pacing
      induced HF.

PMID- 24888399
TI  - High light acclimation of Oryza sativa L. leaves involves specific photosynthetic
      sourced changes of NADPH/NADP+ in the midvein.
AB  - Previous studies have shown that exposure of Arabidopsis leaves to high light
      (HL) causes a systemic acquired acclimation (SAA) response in the vasculature. It
      has been postulated that C4-like photosynthesis in the leaf veins triggers this
      response via the Mehler reaction. To investigate this proposed connection and
      extend SAA to other plants, we examined the redox state of NADPH, ascorbate
      (ASA), and glutathione (GSH) pools; levels and histochemical localization of O2-
      and H2O2 signals; and activities of antioxidant enzymes in the midvein and leaf
      lamina of rice, when they were subjected to HL and low light. The results showed
      that (1) high NADPH/NADP(+) was generated by C4-like photosynthesis under HL in
      the midvein and (2) SAA was colocally induced by HL, as indicated by the combined
      signaling network, including the decrease in redox status of ASA and GSH pools,
      accumulation of H2O2 and O2- signals, and high superoxide dismutase (SOD) and
      ascorbate peroxidase (APX) activities. The high correlations between these
      occurrences suggest that the enhanced NADPH/NADP(+) in HL-treated midveins might
      alter redox status of ASA and GSH pools and trigger H2O2 and O2- signals during
      SAA via the Mehler reaction. These changes in turn upregulate SOD and APX
      activities in the midvein. In conclusion, SAA may be a common regulatory
      mechanism for the adaptation of angiosperms to HL. Manipulation of NADPH/NADP(+)
      levels by C4-like photosynthesis promotes SAA under HL stress in the midvein.

PMID- 24888400
TI  - GC-MS-based metabolite profiling of Cosmos caudatus leaves possessing alpha
      glucosidase inhibitory activity.
AB  - Cosmos caudatus, which is known as "Ulam Raja," is an herbal plant used in
      Malaysia to enhance vitality. This study focused on the evaluation of the alpha
      glucosidase inhibitory activity of different ethanolic extracts of C. caudatus.
      Six series of samples extracted with water, 20%, 40%, 60%, 80%, and 100% ethanol
      (EtOH) were employed. Gas chromatography-mass spectrometry (GC-MS) and orthogonal
      partial least-squares (OPLS) analysis was used to correlate bioactivity of
      different extracts to different metabolite profiles of C. caudatus. The obtained
      OPLS scores indicated a distinct and remarkable separation into 6 clusters, which
      were indicative of the 6 different ethanol concentrations. GC-MS can be
      integrated with multivariate data analysis to identify compounds that inhibit
      alpha-glucosidase activity. In addition, catechin, alpha-linolenic acid, alpha-D
      glucopyranoside, and vitamin E compounds were identified and indicate the
      potential alpha-glucosidase inhibitory activity of this herb. PRACTICAL
      APPLICATION: GC-MS and multivariate data analysis was applied to discriminate
      Cosmos caudatus samples extracted with water and different ratio of ethanol.
      Orthogonal partial least-squares (OPLS) model developed was used to determine the
      major metabolites contributed to alpha-glucosidase inhibitory activity. This
      approach also has the ability to predict the bioactivity of a new set of extracts
      based on a developed validated regression model that is important for quality
      control of the herb preparation.

PMID- 24888401
TI  - Severe flucloxacillin-induced acute generalized exanthematous pustulosis (AGEP),
      with toxic epidermal necrolysis (TEN)-like features: does overlap between AGEP
      and TEN exist? Clinical report and review of the literature.
AB  - Acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome
      (SJS)/toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug
      reactions. Especially in TEN, large areas of the skin and mucosae may become
      detached. Although AGEP and SJS/TEN are distinct entities with a different
      clinical picture, pathogenesis, prognosis and treatment, they may share some
      features, raising the hypothesis of overlap between both entities. We present a
      severe case of AGEP, caused by flucloxacillin, clinically presenting with TEN
      like features and pronounced systemic symptoms with haemodynamic and respiratory
      instability. Furthermore, we present a review of the literature on cases of AGEP
      with features resembling SJS/TEN or a supposed overlap with SJS/TEN. 

PMID- 24888402
TI  - Basal cell carcinoma of the nipple.

PMID- 24888403
TI  - Consequences of patient access restrictions to branded oxycodone hydrochloride
      extended-release tablets on healthcare utilization and costs in US health plans.
AB  - OBJECTIVE: To evaluate the impact of increased access restrictions to branded
      oxycodone hydrochloride extended-release tablets (oxycodone HCl ER), on
      healthcare utilization and costs in patients using extended-release and long
      acting opioids (ER/LA opioids) from the health plan perspective during the period
      from 1/1/2009 to 6/30/2012. METHODS: This retrospective cohort study analyzed
      claims data for adult patients from US plans that increased oxycodone HCl ER
      access restrictions. Study groups were segmented into commercial and Medicare
      payers, and by prior authorization (PA) and tier change (TC) restrictions. Six
      month outpatient visits and prescription utilization and costs were evaluated
      during the pre- and post-access restriction periods using a bootstrapped t-test
      and regression to test the differences. RESULTS: Mean 6-month post-restriction
      combined pharmacy and outpatient visit costs were $1131 (p < 0.001), $660 (p =
      0.009), $699 (p < 0.001), and $564 (p < 0.001) higher than pre-restriction costs
      in commercial PA, commercial TC, Medicare PA, and Medicare TC groups,
      respectively. Outpatient visits accounted for the greatest proportion of
      increased costs in the access restriction groups. CONCLUSIONS: The results of
      this study suggest that oxycodone HCl ER access restrictions such as PA and TC
      may increase medical costs without an offsetting savings in pharmacy costs.

PMID- 24888404
TI  - Diabetic peripheral neuropathy: resource utilization and burden of illness.
AB  - INTRODUCTION: Diabetic peripheral neuropathy (DPN) is a debilitating complication
      of diabetes and accounts for significant morbidity by pre-disposing the foot to
      ulceration and lower extremity amputation. Using a large US commercial claims
      database, this study analyzes the drug class usage and co-morbidities associated
      with DPN as well as estimates the associated economic burden. METHODS: Patients
      older than 18 and diagnosed with DPN were followed longitudinally for 2 years pre
      and post-diagnosis date. Patients were analyzed for age, gender, hospital
      visits, ER and doctor's office visits, pharmacy claims, co-morbidities, and drug
      classes prescribed pre- and post-DPN diagnosis. The economic impact post
      diagnosis of DPN was compared to the patients' pre-diagnosis resource use.
      RESULTS: In total, 10,982 incident DPN patients were identified, with a median
      age of 61 years, and an equal gender distribution. Post-DPN diagnosis, there was
      a 20% increase in the number of patients visiting hospitals and a 46% increase in
      the number of visits to hospitals. Further, there was a 46% increase in the
      annual cost per patient associated with visits to the hospitals, emergency room
      (ER), doctor's office, and pharmacy claims. As per the analysis presented in this
      study, increase in the number of visits, cost per visit, and number of patients
      visiting hospitals, ER and doctor's offices added up to a 46% increase in
      aggregated cost associated with Medical Resource Utilization (MRU) owing to DPN,
      with the highest increase (60%) in costs associated with hospitalization of
      patients with DPN. CONCLUSION: This study highlights the high economic burden
      associated with DPN. The results indicate that resource use significantly
      increases post-diagnosis of DPN, which leads to an increase in costs for payers.
      A noticeable proportion of patients with DPN had a pain co-diagnosis signifying
      the need for treatments that can effectively manage painful DPN.

PMID- 24888406
TI  - Interactive hazards education program for youth in a low SES community: a quasi
      experimental pilot study.
AB  - A pilot study of an interactive hazards education program was carried out in
      Canberra (Australia), with direct input from youth participants. Effects were
      evaluated in relation to youths' interest in disasters, motivation to prepare,
      risk awareness, knowledge indicators, perceived preparedness levels, planning and
      practice for emergencies, and fear and anxiety indicators. Parents also provided
      ratings, including of actual home-based preparedness activities. Using a single
      group pretest-posttest with benchmarking design, a sample of 20 youths and their
      parents from a low SES community participated. Findings indicated beneficial
      changes on a number of indicators. Preparedness indicators increased
      significantly from pre- to posttest on both youth (p < 0.01) and parent ratings
      (p < 0.01). Parent ratings reflected an increase of just under six home-based
      preparedness activities. Youth knowledge about disaster mitigation also was seen
      to increase significantly (p < 0.001), increasing 39% from pretest levels. While
      personalized risk perceptions significantly increased (p < 0.01), anxiety and
      worry levels were seen either not to change (generalized anxiety, p > 0.05) or to
      reduce between pre- and posttest (hazards-specific fears, worry, and distress, ps
      ranged from p < 0.05 to < 0.001). In terms of predictors of preparedness, a
      number of variables were found to predict posttest preparedness levels, including
      information searching done by participants between education sessions. These
      pilot findings are the first to reflect quasi-experimental outcomes for a youth
      hazards education program carried out in a setting other than a school that
      focused on a sample of youth from a low SES community. 

PMID- 24888405
TI  - In vitro and in vivo structure-property relationship of (68)Ga-labeled Schiff
      base derivatives for functional myocardial pet imaging.
AB  - PURPOSE: SPECT (e.g., with (99m)Tc-sestamibi) is routinely used for imaging
      myocardial damage, even though PET could offer a higher spatial resolution. Using
      the generator-gained isotope (68)Ga would allow a rapid supply of the tracer in
      the diagnostic unit. For this reason, the aim of the study was to develop (68)Ga
      labeled PET tracers based on different Schiff base amines and to evaluate the
      cardiomyocyte uptake in vitro as well as the biodistribution of the tracers in
      vivo. PROCEDURES: Fifteen different Schiff bases (basing on 3 different
      backbones) were synthesized and labeled with (68)Ga. Lipophilicity varied between
      0.87 +/- 0.24 and 2.72 +/- 0.14 (logD value). All tracers were positively charged
      and stable in plasma and apo-transferrin solution. In vitro uptake into
      cardiomyocytes was assessed in HL-1 cells in the absence and presence of the
      ionophor valinomycin. In vivo accumulation in the heart and in various organs was
      assessed by small animal PET imaging as well as by ex vivo biodistribution. The
      results were compared with (99m)Tc-sestamibi and (18)F-flurpiridaz. RESULTS: All
      cationic Schiff bases were taken up into cardiomyocytes but the amount varied by
      a factor of 10. When destroying the membrane potential, the cellular uptake was
      markedly reduced in most of the tracers, indicating the applicability of these
      tracers for identifying ischemic myocardium. PET imaging revealed that the in
      vivo myocardial uptake reached a constant value approximately 10 min after
      injection but the intracardial amount of the tracer varied profoundly (SUV 0.46
      to 3.35). The most suitable tracers showed a myocardial uptake which was
      comparable to that of (99m)Tc-sestamibi. CONCLUSIONS: (68)Ga-based Schiff bases
      appear suitable for myocardial PET images with uptake comparable to (99m)Tc
      sestamibi but offering higher spatial resolution. By systematical variation of
      the backbone and the side chains, tracers with optimal properties can be
      identified for further clinical evaluation.

PMID- 24888407
TI  - Knotted multi-length ureteric stents: a case series.

PMID- 24888408
TI  - Expression of Aspergillus niger IA-001 Endo-beta-1,4-xylanase in Pichia pastoris
      and analysis of the enzymic characterization.
AB  - The xylanaseB (XynB) (JX560731.1) gene of Aspergillus niger IA-001 was optimized
      according to the codon usage of Pichia pastoris and expressed in P. pastoris
      GS115. The optimized XynB expression level was increased 2.8 times relative to
      that of the wild-type XynB, and the dual-copy XynB (optimized) expression level
      was increased 1.9 times relative to that of the single-copy XynB (optimized). The
      activity of the dual-copy XynB ((XynB-opt)2) was maximized at 15,158.23 +/- 45.11
      U/mL after 120 h of shaking. The optimal temperature and pH of (XynB-opt)2 were
      50  degrees C and 5.0, respectively. (XynB-opt)2 showed a high specific activity
      of 6,853.00 +/- 20.08 U/mg. IC analysis of the standard xylooligosaccharides
      showed that (XynB-opt)2 was an endo-xylanase with X2 as the main degradation
      product. (XynB-opt)2 was highly specific towards different natural xylans. After
      24 h of hydrolysis, more than 90 % of the total hydrolysis products of xylan were
      X2 and X1, almost no X4 ~ X6. In addition, the enzyme exhibited resistance to
      many metal ions and low pH values. The superior catalytic properties of (XynB
      opt)2 suggested its great potential as an effective additive in animal feed
      industry.

PMID- 24888409
TI  - Exploring the potential binding sites of some known HDAC inhibitors on some HDAC8
      conformers by docking studies.
AB  - We describe the conformational behavior of histone deacetylase 8 (HDAC8) using
      molecular dynamics (MD) simulations. HDAC8 conformers were used for the docking
      studies using some known HDAC inhibitors (HDACi) suberoylanilide hydroxamic acid
      (SAHA), valproic acid (VPA), aroyl-pyrrole-hydroxy-amide (APHA-8) and tubacin to
      explore their interactions, binding modes, free energy values. The MD simulation
      show that HDAC8 make important surface changes at the catalytic site (CS)
      entrance as well as at two entrances locations in the 14-A tunnel. In addition,
      we identify an alternate entrance to the 14-A tunnel named adjacent to the
      catalytic site pocket (ACSP). By using docking studies, it was possible to
      elucidate the importance of hydrophobic and pi-pi interactions that are the most
      important for the ligand-HDAC8 complex structural stabilization. In conclusion,
      the ligand flexibility, molecular weight and chemical moieties (hydroxamic acid,
      aryl and aliphatic moieties) are the principal properties required to increase
      the binding affinity on HDAC8. 

PMID- 24888410
TI  - Thermo- and sulfate-controllable bioelectrocatalysis of glucose based on
      horseradish peroxidase and glucose oxidase embedded in poly(N,N
      diethylacrylamide) hydrogel films.
AB  - Dual-responsive poly(N,N-diethylacrylamide) (PDEA) hydrogel films with entrapped
      horseradish peroxidase (HRP) and glucose oxidase (GOD) were successfully prepared
      on electrode surface with a simple one-step polymerization procedure under mild
      conditions, designated as PDEA-HRP-GOD. Cyclic voltammetric (CV) response of
      electroactive probe K3Fe(CN)6 at the film electrodes displayed reversible thermo-
      and sulfate-responsive switching behavior. For example, at 25  degrees C, the
      K3Fe(CN)6 demonstrated a well-defined CV peak pair with large peak currents for
      the films, showing the on state, while at 40  degrees C, the CV response was
      greatly suppressed and the system was at the off state. The influence of
      temperature and Na2SO4 concentration on the switching behavior of the film system
      was not independent or separated, but was synergetic. The responsive mechanism of
      the system was ascribed to the structure change of PDEA component in the films
      with temperature and sulfate concentration. This switching property of the PDEA
      HRP-GOD films could be further used to realize dual-responsive catalytic
      oxidation of glucose sequentially by HRP and GOD entrapped in the films with
      Fe(CN)6 (3-) as the mediator through changing the surrounding temperature and
      Na2SO4 concentration. This system may establish a foundation for fabricating a
      new type of multi-switchable electrochemical biosensors based on bienzyme
      electrocatalysis. 

PMID- 24888412
TI  - A review of the scope and measurement of postoperative quality of recovery.
AB  - To date, postoperative quality of recovery lacks a universally accepted
      definition and assessment technique. Current quality of recovery assessment tools
      vary in their development, breadth of assessment, validation, use of continuous
      vs dichotomous outcomes and focus on individual vs group recovery. They have
      progressed from identifying pure restitution of physiological parameters to
      multidimensional assessments of postoperative function and patient-focused
      outcomes. This review focuses on the progression of these tools towards an as yet
      unreached ideal that would provide multidimensional assessment of recovery over
      time at the individual and group level. A literature search identified 11 unique
      recovery assessment tools. The Postoperative Quality of Recovery Scale assesses
      recovery in multiple domains, including physiological, nociceptive, emotive,
      activities of daily living, cognition and patient satisfaction. It addresses
      recovery over time and compares individual patient data with base line, thus
      describing resumption of capacities and is an acceptable method for
      identification of individual patient recovery. 

PMID- 24888413
TI  - Nitrogen and transition-metal codoped titania nanotube arrays for visible-light
      sensitive photoelectrochemical water oxidation.
AB  - Vertically aligned titanium dioxide nanotube (TNT) arrays codoped with nitrogen
      and 3d transition metals were successfully fabricated using anodization and
      nitridation processes. The codoping of N and Fe yielded the highest visible-light
      induced photoelectrochemical water oxidation due to bandgap narrowing of impurity
      levels by N and Fe. 

PMID- 24888411
TI  - Human bone chips release of sclerostin and FGF-23 into the culture medium: an in
      vitro pilot study.
AB  - OBJECTIVE: Signaling molecules derived from osteocytes have been proposed as a
      mechanism by which autografts contribute to bone regeneration. However, there
      have been no studies that determined the role of osteocytes in bone grafts.
      MATERIAL AND METHOD: Herein, it was examined whether bone chips and demineralized
      bone matrix release sclerostin and FGF-23, both of which are highly expressed by
      osteocytes. RESULTS: Bone grafts from seven donors were placed in culture medium.
      Immunoassay showed that bone chips released sclerostin (median 1.0 ng/ml) and FGF
      23 (median 9.8 relative units/ml) within the first day, with declining levels
      overtime. Demineralized bone matrix also released detectable amounts of
      sclerostin into culture medium, while FGF-23 remained close to the detection
      limit. In vitro expanded isolated bone cells failed to release detectable amounts
      of sclerostin and FGF-23. CONCLUSION: These results suggest that autografts but
      also demineralized bone matrix can release signaling molecules that are
      characteristically produced by osteocytes.

PMID- 24888414
TI  - New epidemiology of Staphylococcus aureus infection in Asia.
AB  - Not only is Asia the most populous region in the world, but inappropriate
      therapy, including self-medication with over-the-counter antimicrobial agents, is
      a common response to infectious diseases. The high antibiotic selective pressure
      among the overcrowded inhabitants creates an environment that is suitable for the
      rapid development and efficient spread of numerous multidrug-resistant pathogens.
      Indeed, Asia is among the regions with the highest prevalence rates of healthcare
      associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and community
      associated methicillin-resistant S. aureus (CA-MRSA) in the world. Most hospitals
      in Asia are endemic for multidrug-resistant methicillin-resistant S. aureus
      (MRSA), with an estimated proportion from 28% (in Hong Kong and Indonesia) to
      >70% (in Korea) among all clinical S. aureus isolates in the early 2010s.
      Isolates with reduced susceptibility or a high level of resistance to
      glycopeptides have also been increasingly identified in the past few years. In
      contrast, the proportion of MRSA among community-associated S. aureus infections
      in Asian countries varies markedly, from <5% to >35%. Two pandemic HA-MRSA
      clones, namely multilocus sequence type (ST) 239 and ST5, are disseminated
      internationally in Asia, whereas the molecular epidemiology of CA-MRSA in Asia is
      characterized by clonal heterogeneity, similar to that in Europe. In this review,
      the epidemiology of S. aureus in both healthcare facilities and communities in
      Asia is addressed, with an emphasis on the prevalence, clonal structure and
      antibiotic resistant profiles of the MRSA strains. The novel MRSA strains from
      livestock animals have been considered to constitute a public health threat in
      western countries. The emerging livestock-associated MRSA strains in Asia are
      also included in this review.

PMID- 24888415
TI  - Changes of spatial and temporal frequency tuning properties of neurons in the
      middle temporal area of aged rhesus monkeys.
AB  - Aged humans exhibit severe deficits in visual motion perception and contrast
      sensitivity under various levels of spatial and temporal modulation. Previous
      studies indicated that many of these deficits are probably mediated by the neural
      degradation of the central visual system. To clarify the neuronal response
      mechanisms underlying the visual degradation during aging, we examined the
      spatial and temporal frequency tuning properties of neurons from anesthetised and
      paralysed aged monkeys at the middle temporal area (area MT), which is downstream
      of the primary visual cortex in the visual processing pathway and thought to be
      critical for motion perception. We found that the preferred spatial and temporal
      frequencies, spatial resolution and high temporal frequency cutoff of area MT
      neurons were reduced in aged monkeys, and were accompanied by the broadened
      tuning width of spatial frequency, elevated spontaneous activity, and decreased
      signal-to-noise ratio. These results showed that, for neurons in area MT, aging
      significantly changed both the spatial and temporal frequency response tuning
      properties. Such evidence provides new insight into the changes occurring at the
      electrophysiological level that may be related to the aging-related visual
      deficits, especially in processing spatial and temporal information. 

PMID- 24888416
TI  - Meta-analysis on night shift work and risk of metabolic syndrome.
AB  - This study aims to quantitatively summarize the association between night shift
      work and the risk of metabolic syndrome (MetS), with special reference to the
      dose-response relationship with years of night shift work. We systematically
      searched all observational studies published in English on PubMed and Embase from
      1971 to 2013. We extracted effect measures (relative risk, RR; or odd ratio, OR)
      with 95% confidence interval (CI) from individual studies to generate pooled
      results using meta-analysis approach. Pooled RR was calculated using random- or
      fixed-effect model. Downs and Black scale was applied to assess the
      methodological quality of included studies. A total of 13 studies were included.
      The pooled RR for the association between 'ever exposed to night shift work' and
      MetS risk was 1.57 (95% CI = 1.24-1.98, pheterogeneity  = 0.001), while a higher
      risk was indicated in workers with longer exposure to night shifts (RR = 1.77,
      95% CI = 1.32-2.36, pheterogeneity  = 0.936). Further stratification analysis
      demonstrated a higher pooled effect of 1.84 (95% CI = 1.45-2.34) for studies
      using the NCEP-ATPIII criteria, among female workers (RR = 1.61, 95% CI = 1.10
      2.34) and the countries other than Asia (RR = 1.65, 95% CI = 1.39-1.95).
      Sensitivity analysis confirmed the robustness of the results. No evidence of
      publication bias was detected. The present meta-analysis suggested that night
      shift work is significantly associated with the risk of MetS, and a positive dose
      response relationship with duration of exposure was indicated. 

PMID- 24888417
TI  - Retention of cotyledons is crucial for resprouting of clipped oak seedlings.
AB  - Although resprouting plays an important role in facilitating persistence of
      damaged seedlings, the functional attributes of cotyledons and taproots during
      resprouting of 1-year oak seedlings are not well explored. In this study,
      cotyledons were removed from Quercus mongolica seedlings to explore resprouting
      in response to simulated disturbance as a function of shoot clipping, and to
      examine the resprouting ability in relation to timing of clipping and cotyledon
      removal. Isotope labeling experiments were also performed to evaluate
      contribution of the cotyledons and taproots to resprouting. Regardless of timing
      of shoot clipping, seedlings successfully resprouted provided their cotyledons
      were not detached. Clipped seedlings were less likely to resprout when cotyledons
      were removed. Seedlings clipped at earlier development stage exhibited higher
      resprouting capacity than those clipped at later stage. Cotyledon removal, more
      than timing of clipping, decreased the dry masses of newly-resprouted shoots.
      However, no significant influences of cotyledon removal and timing of clipping
      were found on the dry masses of roots, suggesting the importance of cotyledons
      for resprouting. Roots became functional and accumulated more soil nitrogen after
      shoot clipping and cotyledon removal, representing a double security-based
      strategy for the clipped seedlings to resprout despite the importance of
      cotyledons. 

PMID- 24888419
TI  - Facile synthesis of the CERT inhibitor HPA-12 and some novel derivatives.
AB  - HPA-12 is an inhibitor of CERT-mediated non-vesicular transport of ceramide from
      the ER membranes to the Golgi apparatus. The inhibitor effectively blocks the
      synthesis of the membrane lipid sphingomyelin and may represent a novel drug
      prototype. Previous syntheses relied on non-commercial catalysts or specialized
      chemistries. Here we present a straightforward and effective method to synthesize
      HPA-12 from commercially available protected L-serinol in four steps. Some new
      analogues were synthesized and evaluated for their CERT-binding activity. 

PMID- 24888418
TI  - Nativity and cognitive disability among children: a unique comparison with
      reduced selection bias.
AB  - OBJECTIVES: We examined the impact of nativity on self-reported cognitive
      disability by comparing children who were born outside of the USA (first
      generation immigrants) with US-born offspring (second-generation immigrants) of
      foreign-born parents. METHODS: We analyzed a diverse, nationally representative,
      sample of 77,324 first-generation immigrant and second-generation immigrant
      children (aged 5-17 years) from the 2009 American Community Survey. Multivariate
      logistic regression was used to assess the association between nativity and self
      reported cognitive disability after adjustment for demographics and household
      characteristics. RESULTS: Self-reported cognitive disability was observed in 1.7
      % of the sample. The prevalence was higher among first second-generation
      immigrants than among second first-generation immigrants (1.9 vs 1.1 %, p <
      0.001). After multivariate adjustment, the advantage of being foreign-born
      remained (OR = 0.63, 95 % CI = 0.53-0.75). Further analysis revealed effect
      modification of the immigrant health advantage by household income (p = 0.003).
      CONCLUSIONS: We observed an immigrant advantage in self-reported cognitive
      disability; however, it was only evident among economically disadvantaged
      children. Future research should examine the contribution of the accumulation of
      poverty over time to the relationship between nativity and children's health.

PMID- 24888420
TI  - Effects of hydrophobic interaction strength on the self-assembled structures of
      model peptides.
AB  - Stable and ordered self-assembled peptide nanostructures are formed as a result
      of cooperative effects of various relatively weak intermolecular interactions. We
      systematically studied the influence of hydrophobic interaction strength and
      temperature on the self-assembly of peptides with a coarse-grained model by Monte
      Carlo simulations. The simulation results show a rich phase behavior of peptide
      self-assembly, indicating that the formation and morphology of peptide assemblies
      may be tuned by varying the temperature and the strength of hydrophobic
      interactions. There exist optimal combinations of temperature and hydrophobic
      interaction strength where ordered fibrillar nanostructures are readily formed.
      Our simulation results not only facilitate the understanding of the self-assembly
      behavior of peptides at the molecular level, but also provide useful insights
      into the development of fabrication strategies for high-quality peptide fibrils. 

PMID- 24888421
TI  - Ultra-strong and low-density nanotubular bulk materials with tunable feature
      sizes.
AB  - The synthesis of ultralow-density (>5 mg/cm(3) ) bulk materials with
      interconnected nanotubular morphology and deterministic, fully tunable feature
      size, composition, and density is presented. A thin-walled nanotubular design
      realized by employing templating based on atomic layer deposition makes the
      material about 10 times stronger and stiffer than aerogels of the same density. 

PMID- 24888422
TI  - Echocardiographic evaluation of tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF) is a cyanotic heart disease consisting of
      nonrestrictive ventricular septal defect, overriding aorta, pulmonary stenosis,
      and right ventricular hypertrophy. Early total correction is the treatment of
      choice and these patients with repaired TOF are increasingly seen in adult
      practice. This review addresses echocardiographic evaluation of TOF, corrected
      TOF, its sequelae and various complications. A working knowledge of TOF
      assessment is essential for all adult cardiologists and sonographers. 

PMID- 24888423
TI  - Catalytic paradigms: a riddle and a puzzle.

PMID- 24888424
TI  - Targeting the anionic region of human protease-activated receptor 4 inhibits
      platelet aggregation and thrombosis without interfering with hemostasis.
AB  - BACKGROUND: Human platelet activation and aggregation is a complex process. To
      date, many therapies have been developed targeting proteins that mediate this
      process to prevent unwanted activation. However, the current standard of care for
      acute coronary syndromes still has limitations, including bleeding risk.
      OBJECTIVE: To evaluate the protease-activated receptor 4 (PAR4) anionic cluster
      as a viable antiplatelet target by using a polyclonal antibody (CAN12). METHODS:
      We used western blotting, aggregation and secretion ex vivo to evaluate the
      ability of CAN12 to interact with PAR4 and inhibit platelet activation. The
      effects of CAN12 in vivo were evaluated with the Rose Bengal arterial thrombosis
      model and two models of hemostasis. RESULTS: CAN12 was able to interact with
      human PAR4 and delay PAR4 cleavage. In addition, CAN12 inhibited thrombin-induced
      human platelet aggregation and secretion in a dose-dependent manner. The
      specificity of CAN12 was agonist-dependent. In vivo, we determined that CAN12 was
      able to inhibit arterial thrombosis, and, using two independent methods, we found
      that CAN12 did not influence hemostasis. CONCLUSION: Targeting the extracellular
      anionic cluster on PAR4 is a viable novel strategy as an antiplatelet therapy.

PMID- 24888426
TI  - Experienced Carers Helping Others (ECHO): protocol for a pilot randomised
      controlled trial to examine a psycho-educational intervention for adolescents
      with anorexia nervosa and their carers.
AB  - Experienced Carers Helping Others (ECHO) is an intervention for carers of people
      with eating disorders. This paper describes the theoretical background and
      protocol of a pilot multicentre randomised controlled trial that will explore the
      use of two variants of ECHO for improving outcomes for adolescents with anorexia
      nervosa (AN) referred for outpatient care. Adolescent patients and their carers
      (typically parents and close others in a supportive role) will be recruited from
      38 eating disorder outpatient services across the UK. Carers will be randomly
      allocated to receive 'ECHOc' guided self-help (in addition to treatment as
      usual), 'ECHO' self-help only (in addition to treatment as usual) or treatment as
      usual only. Primary outcomes are a summary measure of the Short Evaluation of
      Eating Disorders at 6- and 12-month follow-ups. Secondary outcomes are general
      psychiatric morbidity of AN patients and carer, carers' coping and behaviour, and
      change in healthcare use and costs at 6- and 12-month follow-ups. Therapist
      effects will be examined, and process evaluation of ECHOc will be completed. The
      findings from this pilot trial will be used in preparation for executing a
      definitive trial to determine the impact of the preferred variant of ECHO to
      improve treatment outcomes for AN.

PMID- 24888427
TI  - Low birthweight and elevated levels of lipoprotein(a) in prepubertal children.
AB  - AIM: To evaluate whether healthy prepubertal children with low birthweight (LBW)
      exhibited higher serum levels of lipoprotein(a) (Lp(a)) than did those with
      normal birthweight (NBW). METHODS: A total of 350 healthy children aged 6 to 9
      years and in Tanner stage 1 were enrolled in a community-based cross-sectional
      study. Family history of hypertension, diabetes or cardiovascular disease (CVD)
      in parents and grandparents; active smoking; a diagnosis of acute or chronic
      illness; and intake of vitamins or nutritional supplements were exclusion
      criteria. The cut-off point for Lp(a) was 0.79 MUmol/L. RESULTS: LBW was
      identified in 51 (14.6%) children. In total, 42 (12.0%) children had elevated
      Lp(a) levels, with 25 (49.0%) and 17 (5.7%) in the LBW and NBW groups,
      respectively (P < 0.0005). None of the children had adverse cardiovascular
      outcomes. Average body mass index (BMI) (17.1 +/- 3.3 and 18.8 +/- 3.9, P =
      0.001), glucose levels (4.5 +/- 0.5 and 4.8 +/- 0.4 mmol/L, P = 0.007), insulin
      levels (67.4 +/- 45.1 and 86.1 +/- 54.9 pmol/L, P = 0.02), and Lp(a) levels (0.52
      +/- 0.21 and 1.40 +/- 0.49 MUmol/L, P < 0.0005) were higher in the children with
      LBW than in the children with NBW. A multivariate analysis adjusted by age, sex,
      raw BMI, BMI standard deviation score and insulin level showed a significant
      association between LBW and elevated levels of Lp(a) (odds ratio 8.02, 95%
      confidence interval 7.3-21.3; P < 0.0005). CONCLUSIONS: LBW was shown to be
      strongly associated with elevated serum levels of Lp(a).

PMID- 24888425
TI  - A 'ramp-sprint' protocol to characterise indices of aerobic function and exercise
      intensity domains in a single laboratory test.
AB  - PURPOSE: The lactate threshold (LT), critical power (CP) and maximum oxygen
      uptake (VO2max) together partition exercise intensity domains by their common
      physiological, biochemical and perceptual response characteristics. CP is the
      greatest power output attainable immediately following intolerance at VO2peak,
      and the asymptote of 3 min all-out exercise. Thus we reasoned that a maximal
      'sprint' immediately following standard ramp-incremental exercise would allow
      characterisation of the three aerobic indices in a single test. METHODS: Ten
      healthy men (23 +/- 3 year, mean +/- SD) performed 9 cycle-ergometry tests on
      different days: (A) two ramp-incremental tests to intolerance (20 W min(-1)),
      immediately followed by a 3 min maximal, variable-power effort ramp-sprint test
      (RST) for LT, VO2peak and sprint-phase power (SP) determination; (B) four
      constant-power tests for CP and VO2max determination; (C) constant-power tests at
      10 W below LT, and 10 W below and above SP to verify intensity domain
      characterisation. Capillary [lactate] and breath-by-breath VO2 were measured.
      RESULTS: Reproducibility of LT, SP and VO2max measurements between RST repeats
      was within 5% or less (r >= 0.991, p < 0.001). CP (257 +/- 46 W) was not
      different (p = 0.72) from SP (258 +/- 42 W). Exercise 10 W below LT and SP
      resulted in steady state VO2 and [lactate]. VO2max (4.0 +/- 0.6 L min(-1)), peak
      [lactate] (11 +/- 2 mM) and intolerance were reached 19 +/- 5 min into exercise
      at 10 W above SP. CONCLUSIONS: These data suggest that the key indices of aerobic
      function may be accurately and reliably estimated during a single exercise test.
      This test may provide a basis for simplifying assessment and prescription of
      exercise training and experimental interventions.

PMID- 24888428
TI  - Intravenous thrombolysis outcomes in patients presenting with large vessel acute
      ischemic strokes--CT angiography-based prognosis.
AB  - BACKGROUND AND PURPOSE: To establish outcome rates for patients receiving
      intravenous thrombolysis based on vascular occlusion site. METHODS: This is a
      retrospective analysis of 225 patients who had received intravenous-rt-PA for
      anterior circulation strokes. The occlusion-site was prospectively determined on
      the admission computed tomographic angiography (CTA) and divided into: large
      vessel occlusion (LVO) including patients with an internal carotid artery
      terminus or middle cerebral artery (M1/proximal M2) occlusions and no large
      vessel occlusion (No-LVO; distal M2/M3/ACA) including patients with either distal
      or no occlusions. The primary outcome was the modified Rankin score (mRS) at 90
      days with a good outcome defined by mRS of 0-2.000. RESULTS: There were 114
      (50.7%) patients in the LVO and 111 (49.3%) in the No-LVO group. A good outcome
      was seen in 28 (24.6%) patients in the LVO and 77 (69.4%) patients in the No-LVO
      group (OR .14; 95% CI: .08-.26; P < .0001). Mortality was observed in 13 (11.7%)
      patients in the No-LVO group and 48 (42.1%) patients in the LVO group (OR .18;
      95% CI: .09-.36; P < .0001). Significant hemorrhage was seen in 14 (12.5%)
      patients in the LVO and 0 (0%) patients in the No-LVO group (P < .0001). Older
      age (OR .96; 95% CI: .93-.98; P = .002) and presence of LVO (OR .29; 95% CI: .12
      .68; P = .004) were significant independent predictors of poor outcome.
      CONCLUSION: CTA identification of proximal occlusions is associated with
      significantly poor outcomes in patients receiving intravenous stroke
      thrombolysis.

PMID- 24888429
TI  - Physical ischaemia induced by isometric exercise facilitated collateral
      development in the remote ischaemic myocardium of humans.
AB  - The aim of the present study was to investigate the effects of isometric-handgrip
      induced PIT (physical ischaemia training) on remote coronary recruitment and
      growth. A total of 74 CAD (coronary artery disease) patients were randomly
      assigned to either the IHG (isometric handgrip group) or NEG (non-exercise
      group). Patients in the IHG performed isometric handgrip exercises during 1 min
      of coronary balloon occlusion, whereas patients in the NEG remained sedentary.
      CFI (collateral flow index), HR (heart rate), SBP (systolic blood pressure) and
      DBP (diastolic blood pressure) were evaluated before and at the end of occlusion.
      In a second study, 21 CAD patients were randomly divided into the IHT (isometric
      handgrip training) group or the NTG (non-training group). Patients in the IHT
      group performed 3 months of IHT, whereas patients in the control group remained
      sedentary. SPECT (single-photon emission computed tomography) was used to
      evaluate myocardial perfusion, and VEGF (vascular endothelial growth factor)
      levels were determined using ELISA. In the IHG, CFI was significantly higher than
      in the control group (P<0.01). HR, SBP and DBP in the IHG were significantly
      higher than in the NEG (P<0.01) at the end of occlusion. In the second study,
      myocardial perfusion (P<0.05) and left ventricular ejection fraction (P<0.01)
      were significantly improved in the IHT group. VEGF levels in the IHT group were
      significantly increased (P<0.01). Levels of VEGF were negatively correlated with
      the summed rest score of SPECT (r=-0.60, P<0.01). In conclusion, isometric
      handgrip exercise-induced PIT may promote remote collateral recruitment and
      growth in CAD patients. 

PMID- 24888430
TI  - Is a 'general' theory of addiction possible? A commentary on: a multistep general
      theory of transition to addiction.

PMID- 24888431
TI  - Do those over 80 years of age seek more or less medical help? A qualitative study
      of health and illness beliefs and behaviour of the oldest old.
AB  - Increasing longevity and prevalence of long-term conditions contribute to older
      adults being the greatest users of health services. However, relatively little is
      known about the health and illness beliefs of the oldest old or how they decide
      to seek help in response to symptoms. Through analysis of in-depth interviews
      with day centre attendees aged 80-93, we find that a moral, hierarchical approach
      to health problems and help-seeking exists; similar to Cornwell's (1984) findings
      among 50-60 year-olds of a similar social group 30 years ago. However, when
      acting independently, those in their eighties and nineties report modifying their
      health and illness beliefs and behaviour, in response to their own perceived old
      age. Some health problems are 'demedicalised', being increasingly attributed to
      age and by being self-managed. Others are perceived as potentially more serious,
      leading to increased consultation with medical services. When obliged to act
      outside their moral belief-behaviour framework by others, the participants
      expressed feelings of disempowerment, yet resisted modifying their moral beliefs.
      This may represent resistance to adopt the 'sick role', while seeking to maintain
      control over uncertain health as functional dependence and frailty increases.
      This study furthers theoretical understanding of the health and illness beliefs
      and behaviour of the oldest old, with important practical implications.

PMID- 24888432
TI  - Actin sliding velocity on pure myosin isoforms from hindlimb unloaded mice.
AB  - AIM: Notwithstanding the widely accepted idea that following disuse skeletal
      muscles become faster, an increase in shortening velocity was previously observed
      mostly in fibres containing type 1 myosin, whereas a decrease was generally found
      in fibres containing type 2B myosin. In this study, unloaded shortening velocity
      of pure type 1 and 2B fibres from hindlimb unloaded mice was determined and a
      decrease in type 2B fibres was found. METHODS: To clarify whether the decrease in
      shortening velocity could depend on alterations of myosin motor function, an in
      vitro motility assay approach was applied to study pure type 1 and pure type 2B
      myosin from hindlimb unloaded mice. The latter approach, assessing actin sliding
      velocity on isolated myosin in the absence of other myofibrillar proteins,
      enabled to directly investigate myosin motor function. RESULTS: Actin sliding
      velocity was significantly lower on type 2B myosin following unloading (2.70 +/-
      0.32 MUm s(-1)) than in control conditions (4.11 +/- 0.35 MUm s(-1)), whereas
      actin sliding velocity of type 1 myosin was not different following unloading
      (0.89 +/- 0.04 MUm s(-1)) compared with control conditions (0.84 +/- 0.17 MUm s(
      1)). Myosin light chain (MLC) isoform composition of type 2B myosin from hindlimb
      unloaded and control mice was not different. No oxidation of either type 1 or 2B
      myosin was observed. Higher phosphorylation of regulatory MLC in type 2B myosin
      after unloading was found. CONCLUSION: Results suggest that the observed lower
      shortening velocity of type 2B fibres following unloading could be related to
      slowing of acto-myosin kinetics in the presence of MLC phosphorylation.

PMID- 24888433
TI  - Post-transcriptional control of GRF transcription factors by microRNA miR396 and
      GIF co-activator affects leaf size and longevity.
AB  - The growth-regulating factors (GRFs) are plant-specific transcription factors.
      They form complexes with GRF-interacting factors (GIFs), a small family of
      transcriptional co-activators. In Arabidopsis thaliana, seven out of the nine
      GRFs are controlled by microRNA miR396. Analysis of Arabidopsis plants carrying a
      GRF3 allele insensitive to miR396 revealed a strong boost in the number of cells
      in leaves, which was further enhanced synergistically by an additional increase
      of GIF1 levels. Genetic experiments revealed that GRF3 can still increase cell
      number in gif1 mutants, albeit to a much lesser extent. Genome-wide transcript
      profiling indicated that the simultaneous increase of GRF3 and GIF1 levels causes
      additional effects in gene expression compared to either of the transgenes alone.
      We observed that GIF1 interacts in vivo with GRF3, as well as with chromatin
      remodeling complexes, providing a mechanistic explanation for the synergistic
      activities of a GRF3-GIF1 complex. Interestingly, we found that, in addition to
      the leaf size, the GRF system also affects the organ longevity. Genetic and
      molecular analysis revealed that the functions of GRFs in leaf growth and
      senescence can be uncoupled, demonstrating that the miR396-GRF-GIF network
      impinges on different stages of leaf development. Our results integrate the post
      transcriptional control of the GRF transcription factors with the progression of
      leaf development.

PMID- 24888434
TI  - Elucidating diphosphoinositol polyphosphate function with nonhydrolyzable
      analogues.
AB  - The diphosphoinositol polyphosphates (PP-IPs) represent a novel class of high
      energy phosphate-containing messengers which control a wide variety of cellular
      processes. It is thought that PP-IPs exert their pleiotropic effects as
      allosteric regulators and through pyrophosphorylation of protein substrates.
      However, most details of PP-IP signaling have remained elusive because of a
      paucity of suitable tools. We describe the synthesis of PP-IP bisphosphonate
      analogues (PCP-IPs), which are resistant to chemical and biochemical degradation.
      While the two regioisomers 1PCP-IP5 and 5PCP-IP5 inhibited Akt phosphorylation
      with similar potencies, 1PCP-IP5 was much more effective at inhibiting its
      cognate phosphatase hDIPP1. Furthermore, the PCP analogues inhibit protein
      pyrophosphorylation because of their inability to transfer the beta-phosphoryl
      group, and thus enable the distinction between PP-IP signaling mechanisms. As
      such, the PCP analogues will find widespread applications for the structural and
      biochemical characterization of PP-IP signaling properties. 

PMID- 24888435
TI  - Folliculocentric papules and alopecia.

PMID- 24888437
TI  - Adaptive admixture in the West African bovine hybrid zone: insight from the
      Borgou population.
AB  - Understanding the adaptive response to environmental fluctuations represents a
      central issue in evolutionary biology. Population admixture between divergent
      ancestries has often been considered as an efficient short-term adaptation
      strategy. Cattle populations from the West African Bos taurus * Bos indicus
      hybrid zone represent a valuable resource to characterize the effect of such
      adaptive admixture at the genome level. We here provide a detailed assessment of
      the global and local genome ancestries of the Borgou breed, one of the most
      representative cattle of this hybrid zone. We analysed a large data set
      consisting of 38,100 SNPs genotyped on 203 Borgou and 591 individuals
      representative of all the different cattle ancestries. At the global genomic
      level, we show that Borgou is a stabilized admixed breed whose origin (c. 130
      years ago) traces back to the great African rinderpest pandemic, several
      centuries after the last admixture events, the West African zebus originate from
      (c. 500 years ago). To identify footprints of adaptive admixture, we combined the
      identification of signatures of selection and the functional annotation of the
      underlying genes using systems biology tools. The detection of the SILV coat
      coloration gene likely under artificial selection may be viewed as a validation
      of our approach. Overall, our results suggest that the long-term presence of
      pathogens and the intermediate environmental conditions are the main acting
      selective pressures. Our analytical framework can be extended to other model or
      nonmodel species to understand the process that shapes the patterns of genetic
      variability in hybrid zones.

PMID- 24888436
TI  - An interwoven network of MnO2 nanowires and carbon nanotubes as the anode for
      bendable lithium-ion batteries.
AB  - A porous interwoven network is synthesized, consisting of ultralong MnO2
      nanowires and multi-walled carbon nanotubes (MWCNTs). Serving as the anode for a
      lithium-ion battery, this nanocomposite demonstrates excellent performance due to
      the synergistic integration of these two 1D materials. Taking advantage of the
      excellent flexibility and strength of this MnO2-MWCNT network, a full, bendable
      battery is made that offers high capacity, cycling stability, and low cost.

PMID- 24888438
TI  - The changing face of terrorism in the 21st century: the communications revolution
      and the virtual community of hatred.
AB  - There are no psychological characteristics or psychopathology separating
      terrorists from the general population. Rather, it is group dynamics, with a
      particular emphasis on collective identity, that helps to explain terrorist
      psychology. Just as there is a diverse spectrum of kinds of terrorism, so too is
      there a spectrum of terrorist psychologies. Some terrorists, those in nationalist
      separatist groups, such as Fatah and the IRA, are continuing with the mission of
      their parents who are dissident to the regime. The opposite generational
      provenance is seen among social-revolutionary terrorists, such as the Weather
      Underground and the Red Army Faction in Germany, who are rebelling against their
      parents' generation, which is loyal to the regime. Four waves of terrorism can be
      distinguished: the "anarchist wave"; the "anti-colonial wave" (nationalist
      separatist), with minority groups seeking to be liberated from their colonial
      masters or from the majority in their country; the "new left" wave (social
      revolutionary); and now the "religious" wave. With the communications revolution,
      a new phenomenon is emerging which may presage a fifth wave: lone wolf terrorists
      who through the Internet are radicalized and feel they belong to the virtual
      community of hatred. A typology of lone wolf terrorism is proposed.

PMID- 24888440
TI  - Essential oils: extraction, bioactivities, and their uses for food preservation.
AB  - Essential oils are concentrated liquids of complex mixtures of volatile compounds
      and can be extracted from several plant organs. Essential oils are a good source
      of several bioactive compounds, which possess antioxidative and antimicrobial
      properties. In addition, some essential oils have been used as medicine.
      Furthermore, the uses of essential oils have received increasing attention as the
      natural additives for the shelf-life extension of food products, due to the risk
      in using synthetic preservatives. Essential oils can be incorporated into
      packaging, in which they can provide multifunctions termed "active or smart
      packaging." Those essential oils are able to modify the matrix of packaging
      materials, thereby rendering the improved properties. This review covers up-to
      date literatures on essential oils including sources, chemical composition,
      extraction methods, bioactivities, and their applications, particularly with the
      emphasis on preservation and the shelf-life extension of food products. 

PMID- 24888439
TI  - Dihydroisoxazole inhibitors of Anopheles gambiae seminal transglutaminase AgTG3.
AB  - BACKGROUND: Current vector-based malaria control strategies are threatened by the
      rise of biochemical and behavioural resistance in mosquitoes. Researching
      mosquito traits of immunity and fertility is required to find potential targets
      for new vector control strategies. The seminal transglutaminase AgTG3 coagulates
      male Anopheles gambiae seminal fluids, forming a 'mating plug' that is required
      for male reproductive success. Inhibitors of AgTG3 can be useful both as chemical
      probes of A. gambiae reproductive biology and may further the development of new
      chemosterilants for mosquito population control. METHODS: A targeted library of 3
      bromo-4,5-dihydroxoisoxazole inhibitors were synthesized and screened for
      inhibition of AgTG3 in a fluorescent, plate-based assay. Positive hits were
      tested for in vitro activity using cross-linking and mass spectrometry, and in
      vivo efficacy in laboratory mating assays. RESULTS: A targeted chemical library
      was screened for inhibition of AgTG3 in a fluorescent plate-based assay using its
      native substrate, plugin. Several inhibitors were identified with IC50 < 10 MUM.
      Preliminary structure-activity relationships within the library support the
      stereo-specificity and preference for aromatic substituents in the chemical
      scaffold. Both inhibition of plugin cross-linking and covalent modification of
      the active site cysteine of AgTG3 were verified. Administration of an AgTG3
      inhibitor to A. gambiae males by intrathoracic injection led to a 15% reduction
      in mating plug transfer in laboratory mating assays. CONCLUSIONS: A targeted
      screen has identified chemical inhibitors of A. gambiae transglutaminase 3
      (AgTG3). The most potent inhibitors are known inhibitors of human
      transglutaminase 2, suggesting a common binding pose may exist within the active
      site of both enzymes. Future efforts to develop additional inhibitors will
      provide chemical tools to address important biological questions regarding the
      role of the A. gambiae mating plug. A second use for transglutaminase inhibitors
      exists for the study of haemolymph coagulation and immune responses to wound
      healing in insects.

PMID- 24888443
TI  - Primary cerebral and cerebellar astrocytes display differential sensitivity to
      extracellular sodium with significant effects on apoptosis.
AB  - Central pontine myelinolysis is one of the idiopathic or iatrogenic brain
      dysfunction, and the most common cause is excessively rapid correction of chronic
      hyponatraemia. While myelin disruption is the main pathology, as the diagnostic
      name indicates, a previous study has reported that astrocyte death precedes the
      destruction of the myelin sheath after the rapid correction of chronic low Na(+)
      levels, and interestingly, certain brain regions (cerebral cortex, hippocampus,
      etc.) are specifically damaged but not cerebellum. Here, using primary astrocyte
      cultures derived from rat cerebral cortex and cerebellum, we examined how
      extracellular Na(+) alterations affect astrocyte death and whether the response
      is different between the two populations of astrocytes. Twice the amount of
      extracellular [Na(+) ] and voltage-gated Na(+) channel opening induced
      substantial apoptosis in both populations of astrocytes, while, in contrast, one
      half [Na(+) ] prevented apoptosis in cerebellar astrocytes, in which the Na(+) 
      Ca(2+) exchanger, NCX2, was highly expressed but not in cerebral astrocytes.
      Strikingly, the rapid correction of chronic one half [Na(+) ] exposure
      significantly increased apoptosis in cerebellar astrocytes but not in cerebral
      astrocytes. These results indicate that extracellular [Na(+) ] affects astrocyte
      apoptosis, and the response to alterations in [Na(+) ] is dependent on the brain
      region from which the astrocyte is derived.

PMID- 24888445
TI  - Classification of Listeria monocytogenes persistence in retail delicatessen
      environments using expert elicitation and machine learning.
AB  - Increasing evidence suggests that persistence of Listeria monocytogenes in food
      processing plants has been the underlying cause of a number of human listeriosis
      outbreaks. This study extracts criteria used by food safety experts in
      determining bacterial persistence in the environment, using retail delicatessen
      operations as a model. Using the Delphi method, we conducted an expert
      elicitation with 10 food safety experts from academia, industry, and government
      to classify L. monocytogenes persistence based on environmental sampling results
      collected over six months for 30 retail delicatessen stores. The results were
      modeled using variations of random forest, support vector machine, logistic
      regression, and linear regression; variable importance values of random forest
      and support vector machine models were consolidated to rank important variables
      in the experts' classifications. The duration of subtype isolation ranked most
      important across all expert categories. Sampling site category also ranked high
      in importance and validation errors doubled when this covariate was removed.
      Support vector machine and random forest models successfully classified the data
      with average validation errors of 3.1% and 2.2% (n = 144), respectively. Our
      findings indicate that (i) the frequency of isolations over time and sampling
      site information are critical factors for experts determining subtype
      persistence, (ii) food safety experts from different sectors may not use the same
      criteria in determining persistence, and (iii) machine learning models have
      potential for future use in environmental surveillance and risk management
      programs. Future work is necessary to validate the accuracy of expert and machine
      classification against biological measurement of L. monocytogenes persistence. 

PMID- 24888442
TI  - CA1 subfield contributions to memory integration and inference.
AB  - The ability to combine information acquired at different times to make novel
      inferences is a powerful function of episodic memory. One perspective suggests
      that by retrieving related knowledge during new experiences, existing memories
      can be linked to the new, overlapping information as it is encoded. The resulting
      memory traces would thus incorporate content across event boundaries,
      representing important relationships among items encountered during separate
      experiences. While prior work suggests that the hippocampus is involved in
      linking memories experienced at different times, the involvement of specific
      subfields in this process remains unknown. Using both univariate and multivariate
      analyses of high-resolution functional magnetic resonance imaging (fMRI) data, we
      localized this specialized encoding mechanism to human CA1 . Specifically, right
      CA1 responses during encoding of events that overlapped with prior experience
      predicted subsequent success on a test requiring inferences about the
      relationships among events. Furthermore, we employed neural pattern similarity
      analysis to show that patterns of activation evoked during overlapping event
      encoding were later reinstated in CA1 during successful inference. The
      reinstatement of CA1 patterns during inference was specific to those trials that
      were performed quickly and accurately, consistent with the notion that linking
      memories during learning facilitates novel judgments. These analyses provide
      converging evidence that CA1 plays a unique role in encoding overlapping events
      and highlight the dynamic interactions between hippocampal-mediated encoding and
      retrieval processes. More broadly, our data reflect the adaptive nature of
      episodic memories, in which representations are derived across events in
      anticipation of future judgments.

PMID- 24888446
TI  - Stretching cell morphogenesis during late neurulation and mild neural tube
      defects.
AB  - Neurulation is defined as a process of neural tube closure. Recent reports
      suggested that upon completion of this process the major factors of neurulation
      remain in force at least until the central canal of the neural tube is formed.
      Hence, an idea has been put forward to define the two periods of neurulation:
      early neurulation corresponds to the period of neural tube closure and late
      neurulation corresponds to the period of formation of the central canal. These
      ideas are discussed in a context of neural tube defects that may affect late
      neurulation and result in distention of the central canal. 

PMID- 24888447
TI  - DBAASP: database of antimicrobial activity and structure of peptides.
AB  - The Database of Antimicrobial Activity and Structure of Peptides (DBAASP) is a
      manually curated database for those peptides for which antimicrobial activity
      against particular targets has been evaluated experimentally. The database is a
      depository of complete information on: the chemical structure of peptides; target
      species; target object of cell; peptide antimicrobial/haemolytic/cytotoxic
      activities; and experimental conditions at which activities were estimated. The
      DBAASP search page allows the user to search peptides according to their
      structural characteristics, complexity type (monomer, dimer and two-peptide),
      source, synthesis type (ribosomal, nonribosomal and synthetic) and target
      species. The database prediction algorithm provides a tool for rational design of
      new antimicrobial peptides. DBAASP is accessible at
      http://www.biomedicine.org.ge/dbaasp/.

PMID- 24888448
TI  - Brief communication: The size of the human frontal sinuses in adults presenting
      complete persistence of the metopic suture.
AB  - The notion of absence of the frontal sinuses in human individuals presenting a
      persistence of the metopic suture is considered as classical in many treatises of
      reference; however, precise studies are very rare and even controversial. The
      purpose of this study was thus to provide original data to confirm or refute this
      classical affirmation with the perspective of some original insights into
      biological significance of the frontal sinuses and the factors influencing their
      exceptional polymorphism. The material consisted of 143 dry skulls of adult
      individuals (European Homo sapiens), distributed in two groups: 80 skulls
      presenting a complete frontal closure with total disappearance of the metopic
      suture, and 63 skulls presenting a complete persistence of the metopic suture.
      Each skull was radiographed in oblique projection using the occipitomental view.
      A simple morphological quantification of the sinus size was defined with four
      categories: (1) aplasia, (2) hypoplasia, (3) medium size, (4) hyperplasia.
      Statistically significant difference in frontal sinusal size was found between
      both groups of skulls. Absent and small sinuses were considerably more frequent
      in skulls with persistence of the metopic suture (57.9 vs. 11.9%): small frontal
      sinuses (hypoplasia) were much more frequent (50.8 vs. 9.4%), although the
      frequency of absence of frontal sinuses (aplasia) was only slightly higher (7.1
      vs. 2.5%).

PMID- 24888449
TI  - Downregulation of beta-catenin and Akt signaling is responsible for poor
      proliferation of the late passage of bone marrow mesenchymal stem cells.
AB  - It is well established that mesenchymal stem cells (MSCs) will partially lose
      their proliferative ability with continuous expansion. However, the specific
      mechanisms underlying this effect remain unclear. In the present study, it was
      identified that beta-catenin was downregulated in the late passage (passage 8) of
      bone marrow mesenchymal stem cells (bmMSCs). Following beta-catenin expression,
      the expression of phospho-Akt was also significantly decreased in the late
      passage of bmMSCs. More notably, overexpression of beta-catenin in passage 8 of
      bmMSCs by transfection with pMXs-beta-catenin plasmids, significantly increased
      cell proliferation and Akt expression. These results indicate that the
      downregulation of beta-catenin and Akt signaling may be a critical factor for the
      proliferation of the late passage of bmMSCs. 

PMID- 24888450
TI  - The continuum heterogeneous biofilm model with multiple limiting substrate Monod
      kinetics.
AB  - We describe a novel procedure to estimate the net growth rate of biofilms on
      multiple substrates. The approach is based on diffusion-reaction mass balances
      for chemical species in a continuum biofilm model with reaction kinetics
      corresponding to a Double-Monod expression. This analytical model considers a
      heterogeneous biofilm with variable distributions of biofilm density, activity,
      and effective diffusivity as a function of depth. We present the procedure to
      estimate the effectiveness factor analytically and compare the outcome with
      values obtained by the application of a rigorous numerical computational method
      using several theoretical examples and a test case. A comparison of the profiles
      of the effectiveness factor as a function of the Thiele modulus, phi, revealed
      that the activity of a homogeneous biofilm could be as much as 42% higher than
      that of a heterogeneous biofilm, under the given conditions. The maximum relative
      error between numerical and estimated effectiveness factor was 2.03% at phi near
      0.7 (corresponding to a normalized Thiele modulus phi* = 1). For phi < 0.3 or phi
      > 1.4, the relative error was less than 0.5%. A biofilm containing aerobic
      ammonium oxidizers was chosen as a test case to illustrate the model's
      capability. We assumed a continuum heterogeneous biofilm model where the
      effective diffusivities of oxygen and ammonium change with biofilm position.
      Calculations were performed for two scenarios; Case I had low dissolved oxygen
      (DO) concentrations and Case II had high DO concentrations, with a concentration
      at the biofilm-fluid interface of 10 g O2 /m(3) . For Case II, ammonium was the
      limiting substrate for a biofilm surface concentration, CNs , <=13.84 g of N/m(3)
      . At these concentrations ammonium was limiting inside the biofilm, and oxygen
      was fully penetrating. Conversely, for CNs  > 13.84 g of N/m(3) , oxygen became
      the limiting substrate inside the biofilm and ammonium was fully penetrating.
      Finally, a generalized procedure to estimate the effectiveness factor for a
      system with multiple (n > 2) limiting substrates is given.

PMID- 24888451
TI  - A new strategy for storage and transportation of sensitive high-energy materials:
      guest-dependent energy and sensitivity of 3D metal-organic-framework-based
      energetic compounds.
AB  - Reaction of Co(II) with the nitrogen-rich ligand N,N-bis(1H-tetrazole-5-yl)-amine
      (H2bta) leads to a mixed-valence, 3D, porous, metal-organic framework (MOF)
      based, energetic material with the nitrogen content of 51.78%,
      [Co9(bta)10(Hbta)2(H2O)10]n?(22 H2O)n (1). Compound 1 was thermohydrated to
      produce a new, stable, energetic material with the nitrogen content of 59.85% and
      heat of denotation of 4.537 kcal cm(-3), [Co9(bta)10(Hbta)2(H2O)10]n (2).
      Sensitivity tests show that 2 is more sensitivity to external stimuli than 1,
      reflecting guest-dependent energy and sensitivity of 3D, MOF-based, energetic
      materials. Less-sensitive 1 can be regarded as a more safe form for storage and
      transformation to sensitive 2.

PMID- 24888452
TI  - Sexual dysfunction in men seeking treatment for opioid dependence: a study from
      India.
AB  - INTRODUCTION: There is limited literature on opioid dependence patients for the
      prevalence of sexual dysfunction as assessed by validated questionnaires. AIM: To
      study the prevalence and specified demographic and clinical correlates of sexual
      dysfunction in men seeking treatment for opioid dependence by using multiple
      validated instruments. METHODS: Men with opioid dependence for at least 1 year as
      per DSM-IV (confirmed by Mini International Neuropsychiatric Interview) (OD
      group, N=100) and matched healthy controls (HC group, N=50) were evaluated for
      sexual dysfunction. MAIN OUTCOME MEASURES: Arizona Sexual Experience
      Questionnaire (ASEX), International Index of Erectile Function (IIEF) and Changes
      in Sexual Functioning Questionnaire Short-Form (CSFQ-14). RESULTS: In men seeking
      treatment for opioid dependence sexual dysfunction was recorded in 48% by ASEX,
      and in at least one of the domains in 92% by IIEF and in 90% by CSFQ; in
      comparison with the healthy controls, the prevalence of sexual dysfunction in
      patients with opioid dependence was significantly higher by each measure.
      CONCLUSIONS: Compared with healthy controls, sexual dysfunction rates are higher
      in patients seeking treatment for opioid dependence.

PMID- 24888455
TI  - In vivo evaluation of the dopaminergic neurotransmission system using [123I]FP
      CIT SPECT in 6-OHDA lesioned rats.
AB  - The 6-hydroxydopamine (6-OHDA) rodent model of Parkinson's disease (PD) has been
      used to evaluate the nigrostriatal pathway. The aim of this work was to explore
      the relationship between the degree of 6-OHDA-induced dopaminergic degeneration
      and [(123)I]FP-CIT binding using single photon emission computed tomography
      (SPECT). Fourteen rats received a 6-OHDA injection (4 or 8 ug) into the left
      medial forebrain bundle. After 3 weeks, magnetic resonance imaging and scans with
      a small-animal SPECT system were performed. Finally, the nigrostriatal lesion was
      assessed by immunohistochemical analysis. Immunohistochemical analysis confirmed
      two levels of dopaminergic degeneration. Lesions induced by 6-OHDA diminished the
      ipsilateral [(123)I]FP-CIT binding by 61 and 76%, respectively. The decrease in
      tracer uptake between control and lesioned animals was statistically significant,
      as was the difference between the two 6-OHDA lesioned groups. Results concluded
      that [(123)I]FP-CIT SPECT is a useful technique to discriminate the degree of
      dopaminergic degeneration in a rat model of PD.

PMID- 24888454
TI  - Effects of histone deacetylase inhibition on the survival, proliferation and
      migration of Schwann cells, as well as on the expression of neurotrophic factors
      and genes associated with myelination.
AB  - Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, has been shown to
      have neuroprotective, neurotrophic and anti-inflammatory properties in both
      animal and cellular models of neurodegenerative disorders. In a previous study of
      ours, we demonstrated that TSA inhibited the proliferation and increased the
      differentiation of neuronal precursor cells (NPCs). However, the effects of TSA
      on Schwann cells (SCs) have not yet been fully elucidated. Thus, in the present
      study, using SCs derived from adult rat sciatic nerves, we investigated the
      effects of TSA on the survival, proliferation, migration and myelination of SCs.
      We found that TSA significantly induced SC death when used at high
      concentrations. We also observed that TSA promoted the proliferation of SCs in a
      time-dependent manner. In addition, TSA inhibited the migration of SCs. Moreover,
      RT-PCR revealed that TSA increased the mRNA expression of several neurotrophic
      factors and inhibited the expression of genes associated with myelination,
      including myelin basic protein (MBP) and myelin protein zero (MPZ). Taken
      together, our results suggest that TSA plays an important role in regulating the
      growth and biological function of SCs. These data may contribute to our
      understanding of TSA-based treatment of neurodegenerative diseases.

PMID- 24888457
TI  - Spatiotemporal monitoring of allergic rhinitis symptoms in The Netherlands using
      citizen science.
AB  - BACKGROUND: Airborne pollen is a major symptom trigger in allergic rhinitis
      patients, but the impact of pollen differs among patients and regions and is
      influenced by environmental factors. To study these complex relationships, there
      is a need for data on the severity of symptoms in space and time. 'Citizen
      science' is increasingly recognized as an effective tool to monitor changes in
      our environment. The aim of this study was to investigate the feasibility of a
      citizen science-based survey to monitor spatiotemporal variation in allergic
      rhinitis symptoms. METHODS: Participants were recruited through the Web site
      Allergieradar.nl. After registering by completing an extensive questionnaire,
      they entered (preferably daily) their symptoms of eyes, nose, and lungs on a
      scale from 1 to 10, as well as their geographic location. RESULTS: The
      registration questionnaire revealed that the majority of the participants (77%)
      had physician-diagnosed hay fever and 65% of the participants had been tested
      positively for their allergy. This study shows that the symptom scores of the
      participants are related to (i) pollen concentrations in the air, (ii) the self
      reported sensitivity profile, and (iii) the sales of prescription antihistamines
      in The Netherlands. CONCLUSION: Our data indicate that the collection of allergic
      rhinitis symptom data by 'citizen science' is feasible and has an added value in
      studies on the impact of pollen.

PMID- 24888456
TI  - Are all patients with ductal carcinoma in situ of the breast candidates for
      radiotherapy after breast conservative treatment? Institute of European Oncology
      Guidelines.

PMID- 24888458
TI  - Factors associated with reduced accuracy in Papanicolaou tests for patients with
      invasive cervical cancer.
AB  - BACKGROUND: Recent proposals to lengthen the interval in cervical cancer
      screening highlight the importance of the accurate interpretation of screening
      tests. Tumor debris present in Papanicolaou (Pap) tests from women with invasive
      cancer is known to hamper interpretation. The current study evaluated limiting
      factors in Pap tests from women with invasive cervical cancer. METHODS: A total
      of 3003 women with the spectrum of cervical lesions who had ThinPrep (Hologic
      Inc, Marlborough, Mass) Pap and human papillomavirus (HPV) genotyping tests
      performed were grouped by their most severe histologic diagnosis. Cytologic and
      HPV results were analyzed by cross-sectional analysis. RESULTS: The
      unsatisfactory rate of cytology specimens from patients with cancer (3.1%) was
      significantly higher than those from patients with cervical intraepithelial
      neoplasia of type 3 or less (0.8%) (P < .001). The percentage of samples with
      qualified adequacy was 34.8% in specimens from patients with cancer compared with
      only 3.6% from specimens from those without cancer (P < .001). The unsatisfactory
      and qualified adequacy rates were higher in squamous cancers compared with
      adenocarcinomas. However, adenocarcinomas were identified less frequently than
      squamous cancers (37.0% vs 61.7%) in the Pap tests. HPV tests were positive in
      84.4% of unsatisfactory cases including 8 of 9 cancer cases, although 8.5% of
      cancers tested negative for HPV. CONCLUSIONS: Unsatisfactory and suboptimal
      ThinPrep Pap tests were increased in cancer cases compared with lesser histologic
      diagnoses. This was found to be particularly true for squamous cancers. Specimens
      from adenocarcinomas had fewer adequacy problems but were less frequently
      recognized as malignant. HPV tests were positive in the majority of
      unsatisfactory Pap tests in women with carcinoma, suggesting that HPV testing in
      women aged > 30 years can help to identify high-risk women with unsatisfactory
      Pap tests.

PMID- 24888459
TI  - Assessment of ER Stress and autophagy induced by ionizing radiation in both
      radiotherapy patients and ex vivo irradiated samples.
AB  - Acute radiation leads to several toxic clinical states and triggers some
      molecular pathways. To shed light on molecular mechanisms triggered by ionizing
      radiation (IR), we examined the expression profiles of endoplasmic reticulum (ER)
      stress and autophagy-related genes in individuals who were exposed to IR. Blood
      samples were collected from 50 cancer patients before radiotherapy and on the
      5th, 15th, and 25th days of the treatment. Peripheral blood samples from 10
      healthy volunteers were also obtained for ex vivo irradiation, divided into five
      and irradiated at a rate of 373 kGy/h to 0, 0.1, 0.5, 1, and 3Gy gamma-rays using
      a constant gamma source. GRP78, ATG5, LC3, ATF4, XBP1, and GADD153 genes were
      analyzed by quantitative real-time polymerase chain reaction (QRT-PCR) using beta
      2 microglobulin (B2M) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as
      references. In both groups, expressions of the selected genes have increased. It
      can be concluded that IR induces ER stress and related authophagy pathway in the
      peripheral lymphocyte cells proportionally by dose. 

PMID- 24888460
TI  - Care delivery in youth with type 2 diabetes - are we meeting clinical practice
      guidelines?
AB  - BACKGROUND: Studies indicate high rates of treatment failure and early onset
      diabetes-related complications in youth-onset type 2 diabetes (T2D). We aim to
      describe the quality of care provided to children and youth with T2D. METHODS:
      This prospective cohort study used administrative datasets to describe
      individuals aged 10-24 yr diagnosed with T2D at <20 yr of age (488 individuals;
      2111 person-years). The primary outcome was being 'at goal' for adherence to
      Canadian clinical practice guidelines (CPGs). This was defined as having either
      optimal [three diabetes-related physician visits/year, three hemoglobin A1C (A1C)
      tests/year, and all recommended screening tests for complications (i.e.,
      retinopathy, nephropathy)] or good (two diabetes-related physician visits/year,
      two A1C tests/year, and at least two screening tests) adherence to CPGs.
      Descriptive statistics and logistic regression modeling were used. RESULTS: Sixty
      eight percentage person-years had poor adherence to CPGs (<2 physician visits and
      A1c tests/year and no screening tests). Only 29% and 25% were at goal for
      adherence in the 15-19 and 20-24 yr age groups, respectively. There was a 52%
      decreased odds of being at goal for adherence 4 yr after diagnosis of T2D (p <
      0.001). For every year increase in age at diagnosis, there was a 5% decreased
      odds of being at goal (p = 0.04). CONCLUSIONS: Youth with T2D are not receiving
      high quality care, and older youth and young adults are particularly at risk.
      Future research is needed to understand the effectiveness of care in the context
      of poor adherence as well as patient, physician, and health system factors that
      might improve adherence.

PMID- 24888461
TI  - Venous thromboembolic prophylaxis after a hepatic resection: patterns of care
      among liver surgeons.
AB  - INTRODUCTION: No consensus exists for post-hepatectomy venous thromboembolic
      (VTE) prophylaxis. Factors impacting VTE prophylaxis patterns among hepato
      pancreato-biliary (HPB) surgeons were defined. METHOD: Surgeons were invited to
      complete a web-based survey on VTE prophylaxis. The impact of physician and
      clinical factors was analysed. RESULTS: Two hundred responses were received. Most
      respondents were male (91%) and practiced at academic centres (88%) in the United
      States (80%). Surgical training varied: HPB (24%), transplantation (24%),
      surgical oncology (34%), HPB/transplantation (13%), or no specialty (5%).
      Respondents estimated VTE risk was higher after major (6%) versus minor (3%)
      resections. Although 98% use VTE prophylaxis, there was considerable variability:
      sequential compression devices (SCD) (91%), unfractionated heparin Q12h (31%) and
      Q8h (32%), and low-molecular weight heparin (39%). While 88% noted VTE
      prophylaxis was not impacted by operative indication, 16% stated major resections
      reduced their VTE prophylaxis. Factors associated with the decreased use of
      pharmacologic prophylaxis included: elevated international normalized ratio (INR)
      (74%), thrombocytopaenia (63%), liver insufficiency (58%), large EBL (46%) and
      complications (8%). Forty-seven per cent of respondents wait until >=post
      operative day 1 (POD1) and 35% hold pharmacologic VTE prophylaxis until no signs
      of coagulopathy. A minority (14%) discharge patients on pharmacologic
      prophylaxis. While 81% have institutional VTE guidelines, 79% believe hepatectomy
      specific guidelines would be helpful. CONCLUSION: There is considerable variation
      regarding VTE prophylaxis among liver surgeons. While most HPB surgeons employ
      VTE prophylaxis, the methods, timing and purported contraindications differ
      significantly.

PMID- 24888462
TI  - Epidermolysis bullosa acquisita-like eruption with anticollagen VII
      autoantibodies induced by D-penicillamine in Wilson disease.

PMID- 24888463
TI  - Enantioselective catalysis of the intermolecular [2+2] photocycloaddition between
      2-pyridones and acetylenedicarboxylates.
AB  - Intermolecular [2+2] photocycloadditions represent the most versatile and widely
      applicable of photochemical reactions. For the first time, such intermolecular
      reactions have been carried out in a catalytic fashion using a chiral triplet
      sensitizer, with high enantioselectivity (up to 92% ee). The low catalyst loading
      (2.5-5 mol%) underlines the high efficiency of the process both in terms of
      reaction acceleration and differentiation of the enantiotopic faces of the
      substrate. The substrate is anchored to the chiral catalyst through noncovalent
      interactions (hydrogen bonds), thus providing a chiral environment in which the
      enantioselective photocycloaddition proceeds. The densely functionalized products
      present numerous possibilities for further synthetic transformations.

PMID- 24888464
TI  - Recognition and home care of low birth weight neonates: a qualitative study of
      knowledge, beliefs and practices of mothers in Iganga-Mayuge Health and
      Demographic Surveillance Site, Uganda.
AB  - BACKGROUND: Neonatal mortality has remained persistently high worldwide. In
      Uganda, neonatal deaths account for 50% of all infant deaths. Low birth weight is
      associated with a higher risk of death during the neonatal period. Failure to
      recognize low birth weight and inappropriate home care practices increase the
      risk of morbidity and mortality in this high risk group. This study explored
      mothers' knowledge, beliefs and practices in recognising and providing home care
      for low birth weight babies. METHODS: The study was carried out in Eastern
      Uganda. In-depth interviews were conducted with sixteen mothers of small babies
      who delivered in health facilities (10) or at home (6) two months prior to the
      study. Interviews were conducted in mothers' homes using the local language.
      Interviewer notes and audio recordings were transcribed and translated to
      English. Content analysis was done using Atlas-ti software. RESULTS: Recognition
      of low birth weight by mothers when a baby is not weighed was difficult. Mothers
      were aware of the causes of low birth weight though some mothers believed in the
      influence of supernatural powers. Mothers who delivered in hospital had better
      knowledge of appropriate home care practices for low birth weight babies compared
      to mothers who delivered at home or in a lower level health facility. Practices
      related to cord care and keeping the baby warm were good while poor practices
      were noted concerning initiation and exclusive breast feeding, and bathing the
      baby. Low birth weight was not appreciated as a danger sign in newborns and
      therefore mothers did not seek health care. Some mothers who initiated good care
      practices for low birth weight newborns in the facilities did not sustain them at
      home. CONCLUSIONS: Recognition of low birth weight is still poor. This leads to
      inappropriate home care practices for these high risk newborns. Mothers'
      knowledge and care practices can be improved through health education, and this
      should be extended to the community to reach mothers that deliver at home.
      Mechanisms to support mothers to sustain good practices should be put in place by
      taking advantage of existing village health teams and social support.

PMID- 24888466
TI  - Coexistence of tuberculosis and mammary carcinoma in a goat.
AB  - Synchronic occurrence of tuberculosis mastitis and mammary cancer is rare in
      humans and, to the best of our knowledge, not reported in domestic animals. Here,
      we present a case of a female adult goat of Serrana breed with simultaneous
      occurrence of a granulomatous mastitis, due to Mycobacterium caprae, and a
      mammary carcinoma. Both pathological conditions are rare in goats and should be
      included in differential diagnosis of mammary lesions.

PMID- 24888467
TI  - British Journal of Neurosurgery. Editorial.

PMID- 24888468
TI  - John Bartlett: a tribute to a distinguished and much loved neurosurgeon who
      worked through a period of extraordinary change.

PMID- 24888471
TI  - Possible method to observe the breathing mode of a magnetic domain wall in the
      Josephson  junction.
AB  - A magnetic domain wall (DW) behaves as a massive particle with elasticity.
      Sliding and oscillation of the DW have been observed experimentally, whereas
      vibration of a width in the DW, ?"breathing mode?", has not been measured so far.
      We theoretically propose how to observe the breathing mode by the Josephson
      junction having a ferromagnetic layer between superconducting electrodes. The
      current-voltage (I-V) curve is calculated by an equivalent circuit of the
      resistively shunted junction model. The breathing mode is identified by stepwise
      structures in the I-V curve, which appear at the voltages V = n (h/2e)omega with
      the fundamental constant h/e, integer number n and the frequency of the breathing
      mode omega.

PMID- 24888469
TI  - Reply to letters: Urgent revision required of NICE guidance relating to
      prevention of spread of vCJD through neurosurgical instruments.

PMID- 24888473
TI  - Halogenated flame retardants during egg formation and chicken embryo development:
      maternal transfer, possible biotransformation, and tissue distribution.
AB  - Hen muscle, eggs, and newborn chick tissues (muscle and liver) were collected
      from an electronic waste recycling site in southern China. The authors examined
      the maternal transfer, potential metabolism, and tissue distribution of several
      halogenated flame retardants (HFRs) during egg formation and chicken embryo
      development. The pollutant composition changes significantly from hen muscle to
      eggs and from eggs to tissues of newborn chicks. Higher-halogenated chemicals,
      such as octa- to deca-polybrominated diphenyl ether (PBDE) congeners, deca
      polybrominated biphenyl (PBB209), and dechlorane plus (DP), are less readily
      transferred to eggs compared with lower-halogenated chemicals. During embryo
      development, PBDEs are the most likely to be metabolized, whereas
      decabromodiphenyl ethane (DBDPE) is the least. The authors also observed
      selective maternal transfer of anti-DP and stereoselective metabolism of syn-DP
      during chicken embryo development. During tissue development, liver has greater
      affinity than the muscle for chemcials with a high log octanol-water partition
      coefficient, with the exception of DBDPE. The differences in metabolism potential
      of different chemicals in chicken embryos cause pollutant composition
      alterations. Halogenated flame retardant from maternal transfer and tissue
      distribution also exhibited chemical specificity, especially for DBDPE. Levels of
      DBDPE were elevated along with the full process from hen muscle to eggs and from
      eggs to chick tissues. More attention should be paid to the selective
      accumulation and biotransformation of HFRs in the early development stage of
      birds.

PMID- 24888475
TI  - Does individual experience affect performance during cardiopulmonary
      resuscitation with additional external distractors?
AB  - Cardiopulmonary resuscitation is perceived as a stressful task. Additional
      external distractors, such as noise and bystanders, may interfere with crucial
      tasks and might adversely influence patient outcome. We investigated the effects
      of external distractors on resuscitation performance of anaesthesia residents and
      consultants with different levels of experience. Thirty physicians performed two
      simulated resuscitation scenarios in random order, one scenario without
      additional distractors (control) and one scenario with additional distractors
      (noise, scripted family member). Resuscitation performance was assessed by a
      score based on European Resuscitation Council guidelines, presented as median
      (IQR [range]). We found that performance scores were lower under experimental
      conditions (11.8 (9.0-19.5 [-9.0 to 28.5]) than under control conditions 19.5
      (14.0-25.5 [5.0-29.5]), p = 0.0002). No interaction was observed between
      additional distractors and experience level (p = 0.4480). External distractors
      markedly reduce the quality of cardiopulmonary resuscitation. This suggests that
      all team members, including senior healthcare providers, require training to
      improve performance under stressful conditions.

PMID- 24888474
TI  - Homeostasis and secretion of calcium in the oviductal mucosa of toad Rhinella
      arenarum.
AB  - The presence of a calcium pump, calbindin D-28KD, and calmodulin in the secretory
      cells (SC) of the oviductal pars convoluta (PC) of Rhinella arenarum was
      established for the first time in amphibians using immunohistochemical
      techniques. Marked variations were observed in the localization and degree of
      expression of these proteins according to the duct segment and the period of the
      sexual cycle analyzed. During the preovulatory and ovulatory periods the calcium
      pump colocalized with calbindin D-28KD can be seen mainly in the apical border of
      the SC, which are located in the first zones of PC and synthesize and secrete the
      components of the inner jelly coat layers. These envelopes, which surround the
      oocytes, contain the molecules indispensable for fertilization, probably inducing
      the sperm acrosome reaction (AR). Our results suggest that calmodulin,
      colocalized with the calcium pump at the SC cytoplasmic level, would be involved
      in the active transport of the cation inside the secretory granules, maintaining
      adequate levels of intracellular Ca(2+) . During the postreproductive period, a
      calcium pump colocalized with calbindin D-28KD appears for the first time in the
      cycle in the basal zones of the SC. This system may be related to the
      replenishing of intracellular Ca(2+) stores. In contrast, in R. arenarum the
      Ca(2+) present in the jelly coats that surround the oocytes participates in the
      AR during fertilization, suggesting that this secretion system of the cation
      provided by the oviductal mucosa is functionally more active during the
      reproductive period of this species.

PMID- 24888476
TI  - A rapid extraction and analysis method for the simultaneous determination of 26
      bioflavonoids in Portulaca oleracea L.
AB  - INTRODUCTION: Portulaca oleracea L. (P. oleracea, purslane) is an edible plant
      that is widely distributed around the world, and flavonoids are its main
      bioactive constituents. Therefore, the detection of flavonoids is very important
      for a better understanding of its pharmacological actions and to monitor the
      product quality control of P. oleracea. OBJECTIVE: To develop a rapid method to
      extract and determine 26 bioflavonoids in P. oleracea, based on microwave
      extraction (MWE) and triple quadrupole-linear ion trap mass spectrometry.
      METHODS: The optimal conditions of MWE for the extraction of flavonoids from P.
      oleracea involved the use of methanol as the extraction solvent, a microwave
      power of 300 W, an extraction time of 450 s, and a solvent-to-solid ratio of 30
      mL/g. The samples were analysed using an ultra-performance liquid chromatograph
      coupled with a triple quadrupole-linear ion trap mass spectrometer (UPLC-MS/MS)
      system. RESULTS: The calibration curves of all 26 analytes showed good linearity
      (r >= 0.999) and the intra- and interday precisions and repeatability were all
      within required limits. The mean recoveries measured at three concentrations were
      higher than 94.2%, with RSDs lower than 2.94% for the targets. CONCLUSION: The
      established MWE/UPLC-MS/MS method is a rapid and effective method for quality
      evaluation of P. oleracea from different production regions and different harvest
      periods.

PMID- 24888477
TI  - Trait mindfulness is associated with blood pressure and interleukin-6: exploring
      interactions among subscales of the Five Facet Mindfulness Questionnaire to
      better understand relationships between mindfulness and health.
AB  - Mindfulness based interventions have been associated with improvements in
      physical health; however, the mechanisms underlying these changes are unclear.
      The current study explored relationships between trait mindfulness, blood
      pressure (BP) and interleukin-6 (IL-6). Relationships between physical health
      variables and (1) a composite score of mindfulness, (2) individual facets of
      mindfulness and (3) interactions between theoretically relevant pairs of
      mindfulness subscales were investigated. One hundred and thirty healthy, young
      adults [M (SD) age = 21.7(2.7) years] reported trait levels of mindfulness (Five
      Facet Mindfulness Questionnaire, subscales include: observing, describing, acting
      with awareness (AWA), nonjudging and nonreactivity), had their resting BP
      measured and underwent a blood draw to assesses circulating IL-6 levels. Age,
      gender, body mass index, race/ethnicity, depression and perceived stress were
      obtained and used as covariates. A composite score of trait mindfulness was
      associated with lower BP and a trend suggested that it was also associated with
      lower IL-6. Investigation of individual facets of mindfulness revealed
      interactions between the subscales AWA and nonjudging, such that higher
      endorsement of AWA was associated with lower BP only when nonjudging was also
      high. A second interaction was observed between the subscales observing and
      nonreactivity, such that higher endorsement of observing was associated with
      lower IL-6 only when levels of nonreactivity were also high. Trait mindfulness
      was associated with both BP and IL-6. Examining interactions between facets of
      mindfulness variables may be important in understanding how mindfulness based
      interventions influence physiology.

PMID- 24888478
TI  - Myocyte-mediated arginase expression controls hyperargininemia but not
      hyperammonemia in arginase-deficient mice.
AB  - Human arginase deficiency is characterized by hyperargininemia and infrequent
      episodes of hyperammonemia that cause neurological impairment and growth
      retardation. We previously developed a neonatal mouse adeno-associated viral
      vector (AAV) rh10-mediated therapeutic approach with arginase expressed by a
      chicken beta-actin promoter that controlled plasma ammonia and arginine, but
      hepatic arginase declined rapidly. This study tested a codon-optimized arginase
      cDNA and compared the chicken beta-actin promoter to liver- and muscle-specific
      promoters. ARG1(-/-) mice treated with AAVrh10 carrying the liver-specific
      promoter also exhibited long-term survival and declining hepatic arginase
      accompanied by the loss of AAV episomes during subsequent liver growth. Although
      arginase expression in striated muscle was not expected to counteract
      hyperammonemia, due to muscle's lack of other urea cycle enzymes, we hypothesized
      that the postmitotic phenotype in muscle would allow vector genomes to persist,
      and hence contribute to decreased plasma arginine. As anticipated, ARG1(-/-)
      neonatal mice treated with AAVrh10 carrying a modified creatine kinase-based
      muscle-specific promoter did not survive longer than controls; however, their
      plasma arginine levels remained normal when animals were hyperammonemic. These
      data imply that plasma arginine can be controlled in arginase deficiency by
      muscle-specific expression, thus suggesting an alternative approach to utilizing
      the liver for treating hyperargininemia. 

PMID- 24888480
TI  - Asymmetric synthesis of alpha-amino acids via homologation of Ni(II) complexes of
      glycine Schiff bases. Part 3: Michael addition reactions and miscellaneous
      transformations.
AB  - The major goal of this review is a critical discussion of the literature data on
      asymmetric synthesis of alpha-amino acids via Michael addition reactions
      involving Ni(II)-complexes of amino acids. The material covered is divided into
      two conceptually different groups dealing with applications of: (a) Ni(II)
      complexes of glycine as C-nucleophiles and (b) Ni(II)-complexes of dehydroalanine
      as Michael acceptors. The first group is significantly larger and consequently
      subdivided into four chapters based on the source of stereocontrolling element.
      Thus, a chiral auxiliary can be used as a part of nucleophilic glycine Ni(II)
      complex, Michael acceptor or both, leading to the conditions of matching vs.
      mismatching stereochemical preferences. The particular focus of the review is
      made on the practical aspects of the methodology under discussion and mechanistic
      considerations. 

PMID- 24888479
TI  - WELLFOCUS PPT - modified positive psychotherapy to improve well-being in
      psychosis: study protocol for a pilot randomised controlled trial.
AB  - BACKGROUND: The promotion of well-being is an important goal of recovery oriented
      mental health services. No structured, evidence-based intervention exists that
      aims to increase the well-being in people with severe mental illness such as
      psychosis. Positive psychotherapy (PPT) is a promising intervention for this
      goal. Standard PPT was adapted for use with people with psychosis in the UK
      following the Medical Research Council framework for developing and testing
      complex interventions, resulting in the WELLFOCUS Model describing the intended
      impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting
      the intervention, trial processes, and evaluation strategy. METHODS/DESIGN: This
      study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an
      11-session group therapy in addition to treatment as usual to treatment as usual
      alone. Inclusion criteria are adults (aged 18-65 years) with a main diagnosis of
      psychosis who use mental health services. A target sample of 80 service users
      with psychosis are recruited from mental health services across the South London
      and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the
      intervention and control group. WELLFOCUS PPT is provided to groups by
      specifically trained and supervised local therapists and members of the research
      team. Assessments are conducted before randomisation and after the group
      intervention. The primary outcome measure is well-being assessed by the Warwick
      Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings,
      symptom relief, connectedness, hope, self-worth, empowerment, and meaning.
      Process evaluation using data collected during the group intervention, post
      intervention individual interviews and focus groups with participants, and
      interviews with trial therapists will complement quantitative outcome data.
      DISCUSSION: This study will provide data on the feasibility of the intervention
      and identify necessary adaptations. It will allow optimisation of trial processes
      and inform the evaluation strategy, including sample size calculation, for a
      future definitive RCT. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN04199273 - WELLFOCUS study: an intervention to improve well-being in people
      with psychosis, Date registered: 27 March 2013, first participant randomised on
      26 April 2013.

PMID- 24888482
TI  - Intra-operative guidance: methods for achieving negative margins in breast
      conserving surgery.
AB  - The increasing incidence of breast cancer and advances in detection of small,
      impalpable cancers presents increasing challenges for the modern breast surgeon.
      Accurate localization and excision with adequate oncological margins to reduce
      loco-regional recurrence rates whilst minimizing volume deficit and maximizing
      aesthetics remains the "gold standard." We review the current techniques
      available and the developments within this field.

PMID- 24888483
TI  - Apps in sleep medicine.
AB  - PURPOSE: Users of mobile devices such as iPhones or iPads are offered a wide
      range of applications (apps) regarding sleep and sleep medicine. This article
      will give an overview about the apps that are available. Moreover, it will
      present how they work and determine if they can be used in therapy. METHODS: The
      apps' competence to count snoring noises had to be evaluated. This was done with
      a three-piece test set-up to analyze the apps' ability to distinguish between
      snoring sounds and disturbing noises such as cars driving past the window,
      conversations in the bedroom, or even just the rustling of sheets and blankets.
      RESULTS: The tested apps monitor and record snoring noises well as long as they
      are used in a soundproof environment. In a real-life environment with various
      disturbing noises, the apps show difficulties in telling snoring sounds and other
      noises apart. CONCLUSIONS: The tested apps are not accurate enough to replace the
      common diagnostic standard in therapy. However, they can be a helpful addition.
      Especially, singles could use them who do not know if their snoring has improved
      with an OA and do not have anybody to ask.

PMID- 24888484
TI  - Impression management during evaluation and psychological reactions post-donation
      of living kidney donors.
AB  - Many healthcare providers have been concerned about the extent to which potential
      kidney donors use impression management or concealment of important information
      regarding their medical history, current functioning, or other circumstances that
      could affect whether they are accepted as donors. To date, however, there has
      been very little empirical examination of these questions. It is also not known
      whether donors' use of impression management pre-donation is related to their
      reactions and adjustment post-donation. METHODS: This study surveyed 76
      individuals who had donated a kidney one to six yr previously regarding their use
      of impression management and their concealing of information during their
      psychological evaluations. They were also asked about their reactions to the
      donation and whether they would make the same decision again. In addition, 21 of
      these donors participated in focus groups that explored these questions in depth.
      RESULTS: Many of the kidney donors reported that they possessed very strong
      motivation to donate and consequently used impression management in their
      interactions with medical professionals pre-donation. Very few donors, however,
      indicated that they concealed information during their pre-donation evaluations.
      The donors' psychological reactions post-donation were generally positive, and
      nearly all indicated that they would make the same decision again.

PMID- 24888481
TI  - Comparative genomics of Bradyrhizobium japonicum CPAC 15 and Bradyrhizobium
      diazoefficiens CPAC 7: elite model strains for understanding symbiotic
      performance with soybean.
AB  - BACKGROUND: The soybean-Bradyrhizobium symbiosis can be highly efficient in
      fixing nitrogen, but few genomic sequences of elite inoculant strains are
      available. Here we contribute with information on the genomes of two commercial
      strains that are broadly applied to soybean crops in the tropics. B. japonicum
      CPAC 15 (=SEMIA 5079) is outstanding in its saprophytic capacity and
      competitiveness, whereas B. diazoefficiens CPAC 7 (=SEMIA 5080) is known for its
      high efficiency in fixing nitrogen. Both are well adapted to tropical soils. The
      genomes of CPAC 15 and CPAC 7 were compared to each other and also to those of B.
      japonicum USDA 6T and B. diazoefficiens USDA 110T. RESULTS: Differences in genome
      size were found between species, with B. japonicum having larger genomes than B.
      diazoefficiens. Although most of the four genomes were syntenic, genome
      rearrangements within and between species were observed, including events in the
      symbiosis island. In addition to the symbiotic region, several genomic islands
      were identified. Altogether, these features must confer high genomic plasticity
      that might explain adaptation and differences in symbiotic performance. It was
      not possible to attribute known functions to half of the predicted genes. About
      10% of the genomes was composed of exclusive genes of each strain, but up to 98%
      of them were of unknown function or coded for mobile genetic elements. In CPAC
      15, more genes were associated with secondary metabolites, nutrient transport,
      iron-acquisition and IAA metabolism, potentially correlated with higher
      saprophytic capacity and competitiveness than seen with CPAC 7. In CPAC 7, more
      genes were related to the metabolism of amino acids and hydrogen uptake,
      potentially correlated with higher efficiency of nitrogen fixation than seen with
      CPAC 15. CONCLUSIONS: Several differences and similarities detected between the
      two elite soybean-inoculant strains and between the two species of Bradyrhizobium
      provide new insights into adaptation to tropical soils, efficiency of N2
      fixation, nodulation and competitiveness.

PMID- 24888485
TI  - Pharmacokinetics of micafungin in subjects with severe hepatic dysfunction.
AB  - Micafungin is an echinocandin with potent activity against a broad range of
      fungal species, including Candida species. The pharmacokinetic and safety
      profiles of micafungin have been evaluated in individuals with mild-to-moderate
      hepatic dysfunction, but not in individuals with severe hepatic dysfunction.
      Therefore, the present study assessed the pharmacokinetics and safety of a single
      100 mg dose of micafungin in healthy subjects (n = 8) and subjects with severe
      hepatic dysfunction (n = 8). Mean maximum plasma concentration of micafungin and
      mean area under the plasma micafungin concentration-time curve extrapolated to
      infinity were lower in subjects with severe hepatic dysfunction (7.3 +/- 2.4
      ug/mL and 100.1 +/- 34.5 h.MUg/mL, respectively) than in subjects with normal
      hepatic function (10.3 +/- 2.5 ug/mL and 142.4 +/- 28.9 h.MUg/mL, respectively).
      Mean clearance was higher in subjects with severe hepatic dysfunction (1,098 +/-
      347 mL/h) than in subjects with normal hepatic function (728 +/- 149 mL/h).
      Concentrations of albumin in subjects with severe hepatic dysfunction were lower.
      Assessments of micafungin plasma protein binding suggested that the higher
      clearance in subjects with severe hepatic dysfunction may be due to higher
      unbound concentrations. However, the magnitude of the differences was not
      considered clinically meaningful and is comparable with exposures reported
      elsewhere for a 100-mg dose in patients treated for invasive candidiasis. Thus,
      dose adjustment in subjects with severe hepatic dysfunction is not warranted.
      Micafungin was well tolerated in all subjects throughout the study. 

PMID- 24888486
TI  - Comparative pharmacokinetic interactions of Quercetin and Rutin in rats after
      oral administration of European patented formulation containing Hipphophae
      rhamnoides and Co-administration of Quercetin and Rutin.
AB  - Quercetin and Rutin are most common flavone constituents of some herb extracts
      such as Hippophae rhamnoides L. Inter and intra herb pharmacokinetics
      interactions of Quercetin and Rutin were investigated in the present study.
      Pharmacokinetic study was investigated in the two groups of rats (n = 6) for
      pharmacokinetic interactions between the Quercetin and Rutin (2.5 mg/kg) mixture
      treated alone with European patented polyherbal formulation containing equivalent
      weight of the above. The total plasma concentrations of Quercetin and Rutin were
      determined by liquid chromatography mass spectrometry (LC-MS). A method was
      developed and validated according to the ICH guidelines. The results of the
      present study shows that there are great differences in the pharmacokinetics of
      Quercetin and Rutin when they are administered together and from the polyherbal
      formulation which will be interacted by many other constituents. The
      bioavailability of Quercetin was lowered from the polyherbal formulation when
      compared with the co-administration, whereas the Rutin bioavailability has
      increased from the polyherbal formulation when compared with the co
      administration. The maximum plasma concentration of Quercetin from
      coadministration and polyherbal formulation was 165.3 +/- 31.9 and 90.8 +/- 21.4
      ng/mL, respectively, whereas in the case of Rutin it was 61.1 +/- 29.3 and 121.7
      +/- 19.2 ng/mL. After polyherbal formulation administration to rats the AUC0-24,
      AUC0-infinity and AUMC0-infinity of both Quercetin and Rutin significantly
      increased when compared to co-administration. The above results proved that inter
      and intra herb pharmacokinetic interactions between Quercetin and Rutin. Possible
      interactions of the other constituents with hydrolyzing enzymes in the
      formulation enhances the oral bioavailability of Rutin. Accordingly besides the
      drug herb interactions, inter and intra herb interaction might be brought into
      view with the wide use of herbal remedies.

PMID- 24888487
TI  - Takotsubo syndrome with refractory cardiogenic shock after trauma: successful
      treatment with an intra-aortic balloon pump.

PMID- 24888489
TI  - Efficient water oxidation catalyzed by mononuclear ruthenium(II) complexes
      incorporating Schiff base ligands.
AB  - Four new charge-neutral ruthenium(II) complexes containing dianionic Schiff base
      and isoquinoline or 4-picoline ligands were synthesized and characterized by NMR
      and ESI-MS spectroscopies, elemental analysis, and X-ray diffraction. The
      complexes exhibited excellent chemical water oxidation activity and high
      stability under acidic conditions (pH 1.0) using (NH4)2Ce(NO3)6 as a sacrificial
      electron acceptor. The high catalytic activities of these complexes for water
      oxidation were sustained for more than 10 h at low concentrations. High turnover
      numbers of up to 3200 were achieved. A water nucleophilic attack mechanism was
      proposed. A Ru(V)=O intermediate was detected during the catalytic cycle by high
      resolution mass spectrometry.

PMID- 24888488
TI  - A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus
      best supportive care (BSC) with placebo plus BSC in anemic patients with
      International Prognostic Scoring System low- or intermediate-1-risk
      myelodysplastic syndrome.
AB  - Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia
      of inflammation associated with myelodysplastic syndrome (MDS). This double
      blind, placebo-controlled, phase 2 study assessed the efficacy and safety of
      siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low- and
      intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were
      randomized in a 2:1 ratio to siltuximab 15 mg kg(-1) every 4 weeks + best
      supportive care (BSC) or placebo + BSC for 12 weeks. The primary endpoint was
      reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as
      >=50% relative decrease and >=2-unit absolute decrease in RBC transfusions. Fifty
      and 26 patients were randomized to the siltuximab and placebo groups,
      respectively. The study did not meet its prespecified hypothesis, with six (12%)
      patients in the siltuximab group and one (3.8%) in the placebo group having
      reductions in RBC transfusions (P = 0.271). At the time of the planned futility
      analysis, the prespecified cutoff criteria were not met, and the study was
      terminated early due to lack of efficacy. No unexpected safety findings were
      observed. In conclusion, compared to placebo, treatment with siltuximab did not
      reduce RBC transfusions in transfusion-dependent patients with low- and
      intermediate-1-risk MDS. Future studies might explore siltuximab in patients with
      less iron overload and with elevated IL-6 levels and/or using higher doses for
      MDS.

PMID- 24888490
TI  - Cyclophosphamide inhibits root development of molar teeth in growing mice.
AB  - Root development of permanent teeth is disturbed in survivors of childhood
      cancer. Cyclophosphamide (CY) is a cytostatic drug commonly used for chemotherapy
      in children with cancer. This study aimed to evaluate the effects of CY on the
      development of molar teeth until the completion of occlusion in young mice,
      focusing on Hertwig's epithelial root sheath (HERS). We treated thirty-two 12-day
      old ICR mice with CY (100 mg/kg; 100-CY group), and 36 control mice with saline.
      At 12, 14, 16, 20, 24, 27, 39, 60, and 76 days of age, the mandibular molars were
      removed. Soft X-ray radiographs were obtained in lateral projection. The
      root/crown length (R/C) ratio of the first molar was calculated. Serial sagittal
      sections were prepared and histomorphological hematoxylin and eosin (HE) staining
      and immunohistochemical (cytokeratin) studies were performed. The R/C ratio of
      the 100-CY group (0.78) was smaller than that of the control group (1.23) at 76
      days (p < 0.05, t test). While all roots developed further after injection,
      microscopic examination showed that the roots of the first molars that developed
      in the 100-CY group were shorter than those in the control group. In addition,
      experimental mice showed apical closure of the roots. By 20 days after injection,
      the HERS had disappeared from the root surface in the 100-CY group. In
      conclusion, this study indicates that CY can induce a defect in HERS and cause
      early loss of HERS. Disruption of the epithelial sheath inhibits normal root
      formation, and it could cause irreversible short-root development.

PMID- 24888491
TI  - Alpha-mangostin suppresses IL-6 and IL-8 expression in P. gingivalis LPS
      stimulated human gingival fibroblasts.
AB  - This study aims to investigate the effect of alpha-mangostin on interleukin (IL)
      6 and IL-8 expression in human gingival fibroblasts (HGFs). HGFs were challenged
      with Porphyromonas gingivalis LPS and then treated with various concentrations of
      alpha-mangostin. The cytotoxicity was determined using MTS assay and cytokine
      expressions were evaluated by Real-time PCR and ELISA. The results showed that 5
      MUg/ml P. gingivalis LPS and alpha-mangostin at 1 ug/ml or less did not affect
      the viability of HGFs. Alpha-mangostin reduced IL-6 and IL-8 mRNA and protein in
      P. gingivalis LPS-stimulated HGFs. These findings suggested that alpha-mangostin
      might be used as an adjunct to the periodontal therapy.

PMID- 24888492
TI  - Association of epithelial sodium channel beta-subunit common polymorphism with
      essential hypertension families in a Chinese population.
AB  - The purpose of this study was to investigate whether common polymorphisms in the
      C-terminus of SCNN1B gene encoding the beta-subunit of epithelial sodium channel
      are associated with essential hypertension (EH) in Chinese hypertensive families.
      A total of 433 subjects from 102 EH families were recruited. Biochemical and
      anthropometric indices and systematic screening of the C-terminus of SCNN1B were
      performed. Four single nucleotide polymorphisms (SNPs) were found. Homozygotes
      for the common A allele at rs3743966 had on average a 12.06 mmHg higher SBP and a
      7.43 mmHg higher DBP than homozygotes for the rarer T allele. AA + AT genotype of
      rs3743966 was also found to maybe a risk factor of hypertension by logistic
      regression and transmission/disequilibrium test. AA + AT genotype of rs3743966
      maybe a risk factor of EH. In conclusion, there was a significant association
      between the rs3743966 SNP in intron 12 and EH in Chinese hypertensive families.

PMID- 24888493
TI  - Down-regulation of adiponectin receptors in osteoarthritic chondrocytes.
AB  - The objective of this study was to investigate the expression of adiponectin
      receptors (AdipoR1, R2, and T-cadherin) in both normal subjects and patients with
      knee osteoarthritis (OA). We used immunofluorescence to assess expression of
      adiponectin receptors in the chondrocytes of normal subjects (n = 3) and OA
      patients (n = 3). We also studied mRNA expression of adiponectin receptors in
      both groups by real-time polymerase chain reaction (real-time PCR). Finally, we
      utilized Western blotting to confirm the presence of adiponectin receptors. As
      compared with osteoarthritic chondrocytes, normal chondrocytes showed stronger
      immunoreactivity for AdipoR1, AdipoR2, and T-cadherin. The expression levels of
      both AdipoR1 and AdipoR2 mRNA were significantly lower in the osteoarthritic
      chondrocytes compared with those in the normal chondrocytes, 19 +/- 2 and 36 +/-
      3 % of normal chondrocytes, respectively (P < 0.001). T-cadherin mRNA expression
      levels of the osteoarthritic chondrocytes were also lower than those in the
      normal chondrocytes, but not statistical significant (P = 0.072). The expression
      levels of AdipoR1 and AdipoR2 protein were significantly higher in the normal
      chondrocytes compared with those in the osteoarthritic chondrocytes (P < 0.001, P
      < 0.01, respectively). T-cadherin protein expression level of the normal
      chondrocytes was also higher than those in the osteoarthritic chondrocytes, but
      the difference is not statistical significant (P = 0.114). Expression of
      adiponectin receptors protein in normal and osteoarthritic chondrocytes is
      consistent with its mRNA expression levels. In conclusion, we report for the
      first time down-regulation of adiponectin receptors (AdipoR1, R2, and T-cadherin)
      in osteoarthritic chondrocytes. Decreased adiponectin receptors in OA may reduce
      the tissue sensitivity to adiponectin, thus lost the protection from adiponectin
      in the progression of OA.

PMID- 24888494
TI  - "New turns from old STaRs": enhancing the capabilities of forensic short tandem
      repeat analysis.
AB  - The field of research and development of forensic STR genotyping remains active,
      innovative, and focused on continuous improvements. A series of recent
      developments including the introduction of a sixth dye have brought expanded STR
      multiplex sizes while maintaining sensitivity to typical forensic DNA. New
      supplementary kits complimenting the core STRs have also helped improve analysis
      of challenging identification cases such as distant pairwise relationships in
      deficient pedigrees. This article gives an overview of several recent key
      developments in forensic STR analysis: availability of expanded core STR kits and
      supplementary STRs, short-amplicon mini-STRs offering practical options for
      highly degraded DNA, Y-STR enhancements made from the identification of rapidly
      mutating loci, and enhanced analysis of genetic ancestry by analyzing 32-STR
      profiles with a Bayesian forensic classifier originally developed for SNP
      population data. As well as providing scope for genotyping larger numbers of STRs
      optimized for forensic applications, the launch of compact next-generation
      sequencing systems provides considerable potential for genotyping the sizeable
      proportion of nucleotide variation existing in forensic STRs, which currently
      escapes detection with CE. 

PMID- 24888495
TI  - The effect of nitrogen doping on mercury oxidation/chemical adsorption on the
      CuCo2O4(110) surface: a molecular-level description.
AB  - Based on density functional theory (DFT) calculations, the detailed mercury
      oxidation/chemical adsorption mechanisms on the N-doped CuCo2O4(110) surface are
      studied. The DFT calculations show that Ow (bonded with one Cu(2+) ion and one
      Co(3+) ion) is far more active than Os (bonded with three Co(3+) ions) and the
      mercury oxidation/chemical adsorption activation energy (Ea) on the virgin
      CuCo2O4(110) surface involving Ow is 0.85 eV. The physically adsorbed mercury
      overcomes the Ea and enters the energy well that plays an important role in
      mercury oxidation/chemical adsorption. Nitrogen doping can greatly increase the
      activity of Ow and decrease the activity of Os at the same time, which greatly
      affect the mercury oxidation/chemical adsorption abilities on the CuCo2O4(110)
      surface, and the Ea variation of mercury oxidation/chemical adsorption is as
      follows: 0.85 eV (virgin CuCo2O4(110)) -> 0.76 eV (one N-doped CuCo2O4(110)) ->
      0.69 eV (two N-doped CuCo2O4(110)) -> 0.48 eV (three N-doped CuCo2O4(110)). In
      addition, N-doping can decrease the adsorption energy of mercury and mercuric
      oxide. The effect of N-doping on the bonding mechanism of mercury adsorption on
      the CuCo2O4(110) surface is analyzed by the local density of state (LDOS) and the
      natural bonding orbital (NBO). The calculation results correspond well to the
      experimental data. 

PMID- 24888496
TI  - A bidirectional examination of expressed emotion among families of adolescents
      with bulimia nervosa.
AB  - OBJECTIVE: The purpose of this paper was to examine expressed emotion (EE)
      measured from adolescents with bulimia nervosa (BN) toward their parents, in
      addition to measuring EE from parents toward patients. METHOD: Fifty-four
      adolescents and their parents who were receiving treatment for BN participated in
      a videotaped family interview, from which ratings of EE were made. RESULTS:
      Parent and patient scores were highly correlated. Four family profiles were
      created (Low Patient EE/Low Parent EE; High Patient EE/High Parent EE; Low
      Patient EE/High Parent EE; High Patient EE/Low Parent EE) to determine whether
      the match between parent and patient EE was related to treatment outcome. The Low
      Patient EE/Low Parent EE group demonstrated the greatest reduction in purging
      from baseline to end-of-treatment; the High Patient EE/Low Parent EE group showed
      the smallest reduction in purging. DISCUSSION: EE has historically been rated
      from relatives toward patients, but patients' own EE may also be related to
      treatment outcome.

PMID- 24888497
TI  - Isolating and evaluating lactic acid bacteria strains for effectiveness of Leymus
      chinensis silage fermentation.
AB  - Five LAB strains were evaluated using the acid production ability test,
      morphological observation, Gram staining, physiological, biochemical and acid
      tolerance tests. All five strains (LP1, LP2, LP3, LC1 and LC2) grew at pH 4.0,
      and LP1 grew at 15 degrees C. Strains LP1, LP2 and LP3 were identified as
      Lactobacillus plantarum, whereas LC1 and LC2 were classified as Lactobacillus
      casei by sequencing 16S rDNA. The five isolated strains and two commercial
      inoculants (PS and CL) were added to native grass and Leymus chinensis (Trin.)
      Tzvel. for ensiling. All five isolated strains decreased the pH and ammonia
      nitrogen content, increased the lactic acid content and LP1, LP2 and LP3
      increased the acetic content and lactic/acetic acid ratio of L. chinensis silage
      significantly. The five isolated strains and two commercial inoculants decreased
      the butyric acid content of the native grass silage. LP2 treatment had lower
      butyric acid content and ammonia nitrogen content than the other treatments. The
      five isolated strains improved the quality of L. chinensis silage. The five
      isolated strains and the two commercial inoculants were not effective in
      improving the fermentation quality of the native grass silage, but LP2 performed
      better comparatively. Significance and impact of the study: Leymus chinensis is
      an important grass in China and Russia, being the primary grass of the short
      grassland 'steppe' regions of central Asia. However, it has been difficult to
      make high-quality silage of this species because of low concentration of water
      soluble carbohydrates (WSC). Isolating and evaluating lactic acid bacteria
      strains will be helpful for improving the silage quality of this extensively
      grown species.

PMID- 24888498
TI  - Risk factors for perinatal mortality in patients admitted to the hospital with
      the diagnosis of placental abruption.
AB  - OBJECTIVE: Placental abruption is a clinical term used when premature separation
      of the placenta from the uterine wall occurs prior to delivery of the fetus.
      Hypertension, substance abuse, smoking, intrauterine infection and recent trauma
      are risk factors for placental abruption. In this study, we sought for clinical
      factors that increase the risk for perinatal mortality in patients admitted to
      the hospital with the clinical diagnosis of placental abruption. MATERIALS AND
      METHODS: We identified all placental abruption cases managed over the past 6
      years at our Center. Those with singleton pregnancies and a diagnosis of
      abruption based on strict clinical criteria were selected. Eleven clinical
      variables that had potential for increasing the risk for perinatal mortality were
      selected, logistic regression analysis was used to identify variables associated
      with perinatal death. RESULTS: Sixty-one patients were included in the study with
      16 ending in perinatal death (26.2%). Ethnicity, maternal age, gravidity, parity,
      use of tobacco, use of cocaine, hypertension, asthma, diabetes, hepatitis C,
      sickle cell disease and abnormalities of amniotic fluid volume were not the main
      factors for perinatal mortality. Gestational age at delivery, birthweight and
      history of recent trauma were significantly associated with perinatal mortality.
      The perinatal mortality rate was 42% in patients who delivered prior to 30 weeks
      of gestation compared to 15% in patients who delivered after 30 weeks of
      gestation (p < 0.05). A three-fold increase in severe trauma was reported in the
      group of patients with perinatal mortality than in the group with perinatal
      survivors (25% versus 7%, respectively, p < 0.05). CONCLUSIONS: In patients
      admitted to hospital for placental abruption delivery prior to 30 weeks of
      gestation and a history of abdominal trauma are independent risk factors for
      perinatal death.

PMID- 24888499
TI  - Cisplatin exposure damages resident stem cells of the mammalian inner ear.
AB  - BACKGROUND: Cisplatin is a widely used chemotherapeutic agent that can also cause
      ototoxic injury. One potential treatment for cisplatin-induced hearing loss
      involves the activation of endogenous inner ear stem cells, which may then
      produce replacement hair cells. In this series of experiments, we examined the
      effects of cisplatin exposure on both hair cells and resident stem cells of the
      mouse inner ear. RESULTS: Treatment for 24 hr with 10 uM cisplatin caused
      significant loss of hair cells in the mouse utricle, but such damage was not
      evident until 4 days after the cisplatin exposure. In addition to killing hair
      cells, cisplatin treatment also disrupted the actin cytoskeleton in remaining
      supporting cells, and led to increased histone H2AX phosphorylation within the
      sensory epithelia. Finally, treatment with 10 uM cisplatin appeared to have
      direct toxic effects on resident stem cells in the mouse utricle. Exposure to
      cisplatin blocked the proliferation of isolated stem cells and prevented sphere
      formation when those cells were maintained in suspension culture. CONCLUSION: The
      results suggest that inner ear stem cells may be injured during cisplatin
      ototoxicity, thus limiting their ability to mediate sensory repair.

PMID- 24888501
TI  - Cryosurgery of eyelid basal cell carcinomas including 781 cases treated over 30
      years.
AB  - PURPOSE: To present the results of a 30-year prospective study in which eyelid
      basal cell carcinomas were treated with cryosurgery. METHODS: Basal cell
      carcinomas with well-defined borders on the eyelids or medial canthus, diagnosed
      by punch biopsy, were included. Cryosurgery was performed using liquid nitrogen
      sprayed into a cone circumscribing the tumours. The tumours were treated in a
      double freeze-thaw cycles technique. The minimum thawing time of the frozen area
      outside the tumour margin was at least 60 seconds. During the first 20 years of
      the study, patients were re-examined for up to 10 years. In the last 10 years of
      the study, most patients were followed up for 1 year, and if there was no visible
      scarring in the treated area at the 1-year check-up, follow-ups were implemented
      at the patient's request following self-assessment. RESULTS: In total, 781
      tumours in 768 patients were treated. The median age of the patients at treatment
      was 73 years, mean 70.9 years (range 22-102 years). More women (58%) were treated
      than men. The median tumour size was 8 mm, mean 9.1 mm (range 2-25 mm). There
      were few side-effects requiring intervention. Twelve patients underwent surgery
      due to ektropion during follow-up. In 101 patients, treatment of the tumour
      resulted in conjunctival growth on the skin side, which required correcting
      operations in 28 patients. Three recurrences have occurred. CONCLUSION:
      Cryosurgery is an effective treatment modality for eyelid basal cell carcinomas,
      resulting in few recurrences and good cosmetic and functional outcomes at a low
      cost.

PMID- 24888502
TI  - Clinical evolution of Parkinson's disease and prognostic factors affecting motor
      progression: 9-year follow-up study.
AB  - BACKGROUND AND PURPOSE: There have been few long-term studies that have
      characterized and charted the clinical progression of Parkinson's disease (PD).
      This study was therefore undertaken to understand the natural clinical evolution
      of treated PD patients and to identify the variables that predict greater
      progression in these patients. METHODS: A longitudinal linear mixed model
      analysis of motor score progression was performed on 576 PD patients derived from
      the National Neuroscience Institute Movement Disorders Database. Clinical and
      demographic variables were taken at baseline and formed the subgroups for
      comparison (gender, age at diagnosis, subtype, Mini-Mental State Examination
      score and baseline motor score). Motor score progression was calculated at each
      patient follow-up time point as the difference between Unified Parkinson's
      Disease Rating Scale (UPDRS) motor score at baseline and follow-up scores.
      RESULTS: The overall annual motor score progression as measured by the change of
      UPDRS motor scores from baseline ranged from 0.62% to 3.67%. There are three
      distinct phases: improvement, stability, and steady progression. Patients
      returned to baseline score 2-2.5 years after diagnosis, with stability lasting to
      7 years, followed by a period of steady progression. When analyzed
      longitudinally, male gender (P < 0.03), older age at diagnosis (P < 0.05),
      akinetic-rigid subtype (P < 0.04), cognitive impairment (P < 0.005) and lower
      baseline motor score (P < 0.04) were associated with greater progression of motor
      scores. CONCLUSIONS: Our results show that, when measured clinically, motor
      progression was non-linear and that it occurred in distinct phases, all of which
      were affected by baseline demographic and clinical variables such as gender, age
      at diagnosis, disease subtype, cognitive status and baseline motor score.

PMID- 24888500
TI  - The structural and functional signatures of proteins that undergo multiple events
      of post-translational modification.
AB  - The structural, functional, and mechanistic characterization of several types of
      post-translational modifications (PTMs) is well-documented. PTMs, however, may
      interact or interfere with one another when regulating protein function. Yet,
      characterization of the structural and functional signatures of their crosstalk
      has been hindered by the scarcity of data. To this end, we developed a unified
      sequence-based predictor of 23 types of PTM sites that, we believe, is a useful
      tool in guiding biological experiments and data interpretation. We then used
      experimentally determined and predicted PTM sites to investigate two particular
      cases of potential PTM crosstalk in eukaryotes. First, we identified proteins
      statistically enriched in multiple types of PTM sites and found that they show
      preferences toward intrinsically disordered regions as well as functional roles
      in transcriptional, posttranscriptional, and developmental processes. Second, we
      observed that target sites modified by more than one type of PTM, referred to as
      shared PTM sites, show even stronger preferences toward disordered regions than
      their single-PTM counterparts; we explain this by the need for these regions to
      accommodate multiple partners. Finally, we investigated the influence of single
      and shared PTMs on differential regulation of protein-protein interactions. We
      provide evidence that molecular recognition features (MoRFs) show significant
      preferences for PTM sites, particularly shared PTM sites, implicating PTMs in the
      modulation of this specific type of macromolecular recognition. We conclude that
      intrinsic disorder is a strong structural prerequisite for complex PTM-based
      regulation, particularly in context-dependent protein-protein interactions
      related to transcriptional and developmental processes. AVAILABILITY:
      www.modpred.org.

PMID- 24888503
TI  - Patient-oncologist alliance as protection against suicidal ideation in young
      adults with advanced cancer.
AB  - BACKGROUND: Young adults with cancer are at an increased risk of suicidal
      ideation. To the authors' knowledge, the impact of the patient-oncologist
      alliance on suicidal ideation has not been examined to date. The current study
      examined the relationship between the patient-oncologist therapeutic alliance and
      suicidal ideation in young adults with advanced cancer. METHODS: A total of 93
      young adult patients (aged 20 years-40 years) with incurable, recurrent, or
      metastatic cancer were evaluated by trained interviewers. Suicidal ideation was
      assessed with the Yale Evaluation of Suicidality scale, dichotomized into a
      positive and negative score. Predictors included diagnoses of major depressive
      disorder and posttraumatic stress disorder, physical quality of life, social
      support, and use of mental health and supportive care services. The Human
      Connection Scale, dichotomized into a strong (upper third) and weak (lower two
      thirds) therapeutic alliance, assessed the strength of the patients' perceived
      oncologist alliance. RESULTS: Approximately 22.6% of patients screened positive
      for suicidal ideation. Patients with a strong therapeutic alliance were found to
      be at reduced risk of suicidal ideation after controlling for confounding
      influences of cancer diagnosis, Karnofsky performance status, number of physical
      symptoms, physical quality of life, major depressive disorder, posttraumatic
      stress disorder, and social support. A strong therapeutic alliance was also
      associated with a reduced risk of suicidal ideation after controlling for mental
      health discussions with health care providers and use of mental health
      interventions. CONCLUSIONS: The patient-oncologist alliance was found to be a
      robust predictor of suicidal ideation and provided better protection against
      suicidal ideation than mental health interventions, including psychotropic
      medications. Oncologists may significantly influence patients' mental health and
      may benefit from training and guidance in building strong alliances with their
      young adult patients.

PMID- 24888504
TI  - Chronic N-methyl-D-aspartate receptor activation induces cardiac electrical
      remodeling and increases susceptibility to ventricular arrhythmias.
AB  - BACKGROUND: N-Methyl-d-aspartate receptors, also known as NMDA Receptors or
      NMDAR, are glutamate receptors that control calcium ion channels and regulate
      synaptic plasticity. Acute NMDAR activation can induce ventricular arrhythmias
      (VAs). However, the influence of chronic NMDAR activation on cardiac
      electrophysiology remains unknown. METHODS AND RESULTS: Wistar rats were randomly
      administered 0.9% saline (CTL group), NMDA (N group), or NMDA plus MK801 (N+M
      group) for 14 days. Compared with the CTL group, the N group displayed elevated
      heart rate and prolonged QT, QTc, and TpTe intervals in the electrocardiogram (P
      < 0.05 for all). Then, the S1 S2 , S1 S1 , and Burst pacing were performed to
      assess the characteristics of repolarization; threshold of action potential
      duration (APD) alternans; beat-to-beat variability of repolarization (BVR); and
      VAs susceptibility in the left ventricular. The prolonged APD at 90%
      repolarization (APD90 ); decreased ERP/APD90 ; increased dispersion of APD90 ,
      ERP, and ERP/APD90 ; decreased threshold of APD alternans; increased BVR; and
      incidence of VAs were showed in the N group compared with those of the CTL group
      (P < 0.01 for all). Moreover, chronic NMDA administration reduced the expression
      of Kv4.2, Kv4.3, KChIP2, and Kv11.1 proteins, and induced mild myocardial
      interstitial fibrosis (P < 0.01 for all). Importantly, these alterations induced
      by NMDA were normalized by co-treatment with MK801. CONCLUSION: Chronic NMDAR
      activation prolonged repolarization, induced electrical instability, and
      facilitated VAs, which may be associated with reduced Ito and IKr and myocardial
      fibrosis.

PMID- 24888505
TI  - Stillbirth in twins, exploring the optimal gestational age for delivery: a
      retrospective cohort study.
AB  - OBJECTIVE: To evaluate the optimal gestational age at delivery for twins. DESIGN:
      Retrospective cohort study. SETTING: Database containing demographic, delivery,
      and pregnancy outcome data for over 600,000 births from 81 hospitals in Alberta,
      Canada. POPULATION: All twin births in Alberta, Canada, during 1992-2007, as
      recorded in the databases of the Alberta Perinatal Health Project (www.aphp.ca).
      METHODS: The case files were reviewed for cause of death and any information
      regarding the gestational age at diagnosis of stillbirth. Multivariate logistic
      regression was used to examine the impact of potentially confounding factors. The
      'fetus at risk' approach was used to evaluate the prospective risk of stillbirth.
      Competing risks of stillbirth and neonatal death were evaluated with a perinatal
      risk ratio. RESULTS: Of a total of 17,724 twin births there were 236 antepartum
      stillbirths, 26 intrapartum stillbirths, and 244 neonatal deaths. The rate of
      stillbirth peaked at 7.0/1000 fetuses at risk at 38 weeks of gestation. On
      multivariate analysis, small for gestational age (odds ratio, OR 2.2; 95%
      confidence interval, 95% CI 1.35-3.59), birthweight discrepancy >20% (OR 2.67,
      95% CI 1.42-5.03), and an interaction between these two variables (OR 2.94, 95%
      CI 1.31-6.59), were significant. The perinatal risk ratio suggested that the
      risks of delivery and expectant management were balanced at 36 weeks of gestation
      (RR 0.6, 95% CI 0.1-5.4), but the confidence interval included one, the null
      value, until 38 weeks of gestation (RR 0.1, 95% CI 0.02-0.40). The majority of
      stillbirths at term (14/25) occurred in monochorionic diamniotic twins. The
      estimated risk of stillbirth in this group was 2.3/1000 fetuses at risk at 37
      weeks of gestation, and 17.4/1000 fetuses at risk at 38 weeks of gestation.
      CONCLUSIONS: The balance of risk between neonatal death/intrapartum stillbirth
      and antepartum stillbirth begins to favour delivery at 36 weeks of gestation,
      particularly in monochorionic diamniotic twins.

PMID- 24888506
TI  - Diabetic kidney disease in Australia: current burden and future projections.
AB  - Diabetes mellitus is now the most common cause of new cases of end-stage kidney
      disease treated with kidney replacement therapy in Australia. In addition to the
      approximately 5000 Australians receiving maintenance dialysis or living with a
      kidney transplant as a consequence of diabetes, many die from untreated end-stage
      kidney disease due to diabetes (DM-ESKD) each year. For every Australian
      receiving renal replacement therapy due to diabetes, at least 50 others have
      earlier stages of diabetic kidney disease (DKD). Based on projected increases in
      type 2 diabetes prevalence, the size of this underlying population with DKD will
      potentially exceed half a million by 2025. In addition to the risk of developing
      DM-ESKD, this population is at increased risk of premature cardiovascular
      morbidity and all-cause mortality. Higher rates of hospitalization, use of
      specialist services and prescription drugs mean that those with DKD also incur
      significantly greater health care costs compared with those with diabetes or
      chronic kidney disease alone. However, in contrast to the increasing prevalence
      of diabetes and early stages of DKD, recent trends in the incidence of DM-ESKD
      suggest that better management in the earlier stages of DKD has been successful
      in slowing rates of disease progression. Simultaneous improvements in use of
      renin-angiotensin inhibitors and improved glycaemic and blood pressure control
      are likely to be largely responsible for this trend. Primary prevention,
      maximizing early detection of DKD and optimal management of diabetes and kidney
      disease hold great potential to attenuate the future health burden attributable
      to DKD in Australia. 

PMID- 24888507
TI  - Bone remodeling at implants with different configurations and placed immediately
      at different depth into extraction sockets. Experimental study in dogs.
AB  - OBJECTIVES: This study evaluated the effect of implant macrodesign and position,
      related to the bone crest, on bone-to-implant contact (BIC) and crestal bone (CB)
      in immediate implants. MATERIAL AND METHODS: The study comprised of six foxhound
      dogs in which 48 immediate implants were placed. Three types of implants from the
      same manufacturer with similar surface characteristics but different macrodesigns
      were randomly placed: Group A (external hex with no collar microthreads), Group B
      (internal hex and collar microrings), and Group C (internal conical connection
      and collar microrings). Half of the implants were placed leveled with the bone
      crest (control) and the remaining, 2 mm subcrestally (test). Block sections were
      obtained after 12 weeks and processed for mineralized ground sectioning.
      Statistical analysis consisted of nonparametric Friedman and Wilcoxon test.
      RESULTS: All implants were clinically stable and histologically osseointegrated.
      Mean BIC percentage within the control group was as follows: A: 42.52 +/- 8.67,
      B: 35.19 +/- 18.12, and C: 47.46 +/- 11.50. Within the test group: A: 47.33 +/-
      5.23, B: 48.38 +/- 11.63, and C: 54.88 +/- 11.73. Differences between each
      subgroup in the test and the control groups were statistically significant. BIC
      was statistically significantly higher in the test (50.588 +/- 8.663) than in the
      control (43.317 +/- 9.851) group. Within both groups, differences between group C
      and the other 2 were statistically significant. Distance from the implant
      shoulder to the buccal CB was statistically significantly larger in the control
      than in the test group and between subgroups B and C in the control and test
      groups. Within the test groups, relative bone gain was noticed. CONCLUSIONS:
      Subcrestal immediate implant positioning may lead to a relatively reduced CB
      resorption and increased BIC. Implants macrodesign with crestal microrings may
      enhance BIC in post-extraction implants.

PMID- 24888508
TI  - Studying ongoing and spontaneous pain in rodents--challenges and opportunities.
AB  - The measurement of spontaneous ongoing pain in rodents is a multiplex issue and a
      subject of extensive and longstanding debate. Considering the need to align
      available rodent models with clinically relevant forms of pain, it is of prime
      importance to thoroughly characterize behavioral outcomes in rodents using a
      portfolio of measurements that are not only stimulus-dependent but also encompass
      voluntary behavior in unrestrained animals. Moreover, the temporal course and
      duration of behavioral tests should be taken into consideration when we plan our
      studies to measure explicit chronic pain, with a particular emphasis on
      performing longitudinal studies in rodents. While using rodents as model
      organisms, it is also worth considering their circadian rhythm and the influence
      of the test conditions on the behavioral results, which are affected by social
      paradigms, stress and anxiety. In humans, general wellbeing is closely related to
      pain perception, which also makes it necessary in rodents to consider modulators
      as well as readouts of overall wellbeing. Optimizing the above parameters in
      study design and the new developments that are forthcoming to test the affective
      motivational components of pain hold promise in solving inconsistencies across
      studies and improving their broad applicability in translational research. In
      this review, we critically discuss a variety of behavioral tests that have been
      developed and reported in recent years, attempt to weigh their benefits and
      potential limitations, and discuss key requirements and challenges that lie ahead
      in measuring ongoing pain in rodent models. 

PMID- 24888509
TI  - One problem.

PMID- 24888510
TI  - Cortico-subcortical metabolic correlates of olfactory processing in healthy
      resting subjects.
AB  - A wide network of interconnected areas was previously found in neuroimaging
      studies involving normal as well as pathological subjects; however literature
      seems to suffer from a lack of investigation in glucose metabolism behaviour
      under olfactory condition. Thus, the present work describe for the first time a
      pure olfactory related brain response of metabolism by using (18)F
      fluorodeoxyglucose-Positron Emission Tomography/Computer Tomography in eleven
      resting subjects undergoing a neutral and a pure olfactory condition. By
      contrasting these experimental phases, it was possible to depict a re
      organization pattern of default mode network structures in a relatively
      ecological environment. Moreover, by correlating such pattern with a battery of
      validated olfactory and neuropsychological tests, our work allowed in showing
      peculiar correlation data that could cluster the subjects sample in a certain
      range of normality. We believe the present study could integrate the current
      knowledge in olfactory research and could be a start-up for future contributions.

PMID- 24888512
TI  - Commentary on "late bone and soft tissue sequelae of childhood radiotherapy".

PMID- 24888513
TI  - Foam clogging.
AB  - To what extent are aqueous foams prone to clogging? Foam permeability is measured
      as a function of particulate loading (trapped hydrophilic particles) under
      conditions where the particle to bubble size ratio is allowed to increase when
      the number of particles per bubble is fixed. In addition to experiments performed
      on the foam scale, we investigated experimentally and numerically the
      hydrodynamic resistance of a single foam node loaded with one particle. It is
      shown that, with respect to solid porous media, aqueous foams clog more
      efficiently due to two reasons: (i) the deformation of interfaces allows for
      larger particles to be incorporated within the interstitial network and (ii) the
      interfacial mobility contributes to lowering of the reduced permeability. 

PMID- 24888511
TI  - DEGRO practical guidelines for radiotherapy of breast cancer IV: radiotherapy
      following mastectomy for invasive breast cancer.
AB  - BACKGROUND AND PURPOSE: Since the last recommendations from the Breast Cancer
      Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008,
      evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown.
      This growth is based on updates of the national S3 and international guidelines,
      as well as on new data and meta-analyses. New aspects were considered when
      updating the DEGRO recommendations. METHODS: The authors performed a
      comprehensive survey of the literature. Data from recently published (meta
      )analyses, randomized clinical trials and international cancer societies'
      guidelines yielding new aspects compared to 2008 were reviewed and discussed. New
      aspects were included in the current guidelines. Specific issues relating to
      particular PMRT constellations, such as the presence of risk factors
      (lymphovascular invasion, blood vessel invasion, positive lymph node ratio >20 %,
      resection margins <3 mm, G3 grading, young age/premenopausal status,
      extracapsular invasion, negative hormone receptor status, invasive lobular
      cancer, size >2 cm or a combination of >= 2 risk factors) and 1-3 positive lymph
      nodes are emphasized. RESULTS: The evidence for improved overall survival and
      local control following PMRT for T4 tumors, positive resection margins, >3
      positive lymph nodes and in T3 N0 patients with risk factors such as
      lymphovascular invasion, G3 grading, close margins, and young age has increased.
      Recently identified risk factors such as invasive lobular subtype and negative
      hormone receptor status were included. For patients with 1-3 positive lymph
      nodes, the recommendation for PMRT has reached the 1a level of evidence.
      CONCLUSION: PMRT is mandatory in patients with T4 tumors and/or positive lymph
      nodes and/or positive resection margins. PMRT should be strongly considered in
      patients with T3 N0 tumors and risk factors, particularly when two or more risk
      factors are present.

PMID- 24888515
TI  - Editorial overview: Respiratory: GPCR signaling and the lung.

PMID- 24888514
TI  - Surviving the infarct: A profile of cardiac myosin binding protein-C
      pathogenicity, diagnostic utility, and proteomics in the ischemic myocardium.
AB  - Cardiac myosin binding protein-C (cMyBP-C) is a regulatory protein of the
      contractile apparatus within the cardiac sarcomere. Ischemic injury to the heart
      during myocardial infarction (MI) results in the cleavage of cMyBP-C in a
      phosphorylation-dependent manner and release of an N-terminal fragment (C0C1f)
      into the circulation. C0C1f has been shown to be pathogenic within cardiac
      tissue, leading to the development of heart failure. Based on its high levels and
      early release into the circulation post-MI, C0C1f may serve as a novel biomarker
      for diagnosing MI more effectively than current clinically used biomarkers. Over
      time, circulating C0C1f could trigger an autoimmune response leading to
      myocarditis and progressive cardiac dysfunction. Given the importance of cMyBP-C
      phosphorylation state in the context of proteolytic cleavage and release into the
      circulation post-MI, understanding the posttranslational modifications (PTMs) of
      cMyBP-C would help in further elucidating the role of this protein in health and
      disease. Accordingly, recent studies have implemented the latest proteomics
      approaches to define the PTMs of cMyBP-C. The use of such proteomics assays may
      provide accurate quantitation of the levels of cMyBP-C in the circulation
      following MI, which could, in turn, demonstrate the efficacy of using plasma
      cMyBP-C as a cardiac-specific early biomarker of MI. In this review, we define
      the pathogenic and potential immunogenic effects of C0C1f on cardiac function in
      the post-MI heart. We also discuss the most advanced proteomics approaches now
      used to determine cMyBP-C PTMs with the aim of validating C0C1f as an early
      biomarker of MI. 

PMID- 24888517
TI  - Population genetic data on 15 autosomal STR loci in Bangladeshi population.

PMID- 24888516
TI  - Environmental and socio-demographic associates of children's active transport to
      school: a cross-sectional investigation from the URBAN Study.
AB  - BACKGROUND: Active transport (e.g., walking, cycling) to school (ATS) can
      contribute to children's physical activity and health. The built environment is
      acknowledged as an important factor in understanding children's ATS, alongside
      parental factors and seasonality. Inconsistencies in methodological approaches
      exist, and a clear understanding of factors related to ATS remains equivocal. The
      purpose of this study was to gain a better understanding of associates of
      children's ATS, by considering the effects of daily weather patterns and
      neighbourhood walk ability and neighbourhood preferences (i.e., for living in a
      high or low walkable neighbourhood) on this behaviour. METHODS: Data were drawn
      from the Understanding Relationships between Activity and Neighbourhoods study, a
      cross-sectional study of physical activity and the built environment in adults
      and children in four New Zealand cities. Parents of participating children
      completed an interview and daily trip diary that assessed their child's mode of
      travel to school, household and individual demographic information, and parental
      neighbourhood preference. Daily weather data were downloaded from New Zealand's
      national climate database. Geographic information systems-derived variables were
      calculated for distance to school and neighbourhood walkability. Bivariate
      analyses were conducted with ATS and potential associates; factors related to ATS
      at p < 0.20 were considered simultaneously in generalized estimation equation
      models, and backwards elimination of non-significant factors was conducted; city
      was treated as a fixed effect in all models. RESULTS: A total of 217 children
      aged 6.5-15 years participated in this study. Female sex, age, city, household
      income, limited/no car access, residing in zone of school, shorter distance to
      school, neighbourhood self selection, rainfall, and sunlight hours were
      simultaneously considered in multivariate generalised estimation equation
      modelling (all p < 0.20 in bivariate analyses). After elimination of non
      significant factors, age (p = 0.005), shorter distance to school (p < 0.001),
      city (p = 0.03), and neighbourhood self selection (p = 0.04) remained
      significantly associated with ATS in the multivariate analysis. CONCLUSION:
      Distance to school is the prevailing environmental influencing factor on
      children's ATS. This study, in conjunction with previous research, suggests that
      school siting is likely an important associate of children's ATS.

PMID- 24888518
TI  - New CODIS core loci allele frequencies for 96,400 Brazilian individuals.
AB  - We have reported the allele frequencies of 15 STR loci, including the original 13
      CODIS core loci, in over 100,000 Brazilian individuals. A new CODIS core loci has
      been proposed, but the recently established Brazilian Integrated Network of DNA
      Databases made a decision in 2010 to postpone the implementation of this new set
      of loci due to the lack of allele frequency data for the Brazilian population. We
      aimed to report allele frequencies of 20 loci, estimated from 96,400 Brazilian
      individuals undergoing paternity testing during 2011-2013. The percentage of
      missing data was less than 0.6% for all loci, except for CSF1PO (3.15%) and
      D7S820 (2.5%). The dropout rates estimated by the MicroDrop software were 0.013
      for CSF1PO, 0.000037 for D7S820 and less than 0.000001 for other loci. Small
      missing data percentages and dropout rates reflect the high quality of the data. 

PMID- 24888519
TI  - Paths to first treatment and duration of untreated illness in anorexia nervosa:
      are there differences according to age of onset?
AB  - This study examined paths to first treatment and the duration of untreated
      illness in 140 anorexia nervosa patients using validated questionnaires and a
      clinical interview. The differences between individuals with an early (<=14
      years, n = 40), intermediate (15-18 years, n = 53) and late onset (>=19 years, n
      = 47) were investigated. Participants were most commonly informed about their
      diagnosis and first treatment facility through general practitioners and
      paediatricians. The duration of untreated illness exceeded 2 years in the
      complete sample (25.14 months) and was longest for individuals with an early
      onset. The early onset group was more often externally vs. internally motivated
      and more frequently informed about treatment options by their social network,
      e.g. parents, than patients with a late onset. The results emphasize the
      relevance of training general practitioners and paediatricians about anorexia,
      the need to include parents and teachers in eating disorder prevention and to
      improve targeting young individuals in early interventions.

PMID- 24888520
TI  - Metastatic Crohn's disease: a review and approach to therapy.
AB  - Metastatic Crohn's disease (CD) is a rare cutaneous manifestation of CD that was
      first described nearly 50 years ago. Many subsequent reports have defined its
      most common clinical and histopathologic features. The pathogenesis underlying
      metastatic CD is unknown but various hypotheses exist. An established standard
      therapy is lacking. Owing to its rarity and nonspecific clinical presentation
      along with the diversity of inflammatory skin disorders that often complicate CD,
      the diagnosis of metastatic CD may be overlooked. This report highlights the
      salient features of this disorder to facilitate recognition and management of
      this rare dermatosis. 

PMID- 24888521
TI  - Integrin-linked kinase regulates the rate of platelet activation and is essential
      for the formation of stable thrombi.
AB  - BACKGROUND: Integrin-linked kinase (ILK) and its associated complex of proteins
      are involved in many cellular activation processes, including cell adhesion and
      integrin signaling. We have previously demonstrated that mice with induced
      platelet ILK deficiency show reduced platelet activation and aggregation, but
      only a minor bleeding defect. Here, we explore this apparent disparity between
      the cellular and hemostatic phenotypes. METHODS: The impact of ILK inhibition on
      integrin alphaII b beta3 activation and degranulation was assessed with the ILK
      specific inhibitor QLT0267, and a conditional ILK-deficient mouse model was used
      to assess the impact of ILK deficiency on in vivo platelet aggregation and
      thrombus formation. RESULTS: Inhibition of ILK reduced the rate of both
      fibrinogen binding and alpha-granule secretion, but was accompanied by only a
      moderate reduction in the maximum extent of platelet activation or aggregation in
      vitro. The reduction in the rate of fibrinogen binding occurred prior to
      degranulation or translocation of alphaII b beta3 to the platelet surface. The
      change in the rate of platelet activation in the absence of functional ILK led to
      a reduction in platelet aggregation in vivo, but did not change the size of
      thrombi formed following laser injury of the cremaster arteriole wall in ILK
      deficient mice. It did, however, result in a marked decrease in the stability of
      thrombi formed in ILK-deficient mice. CONCLUSION: Taken together, the findings of
      this study indicate that, although ILK is not essential for platelet activation,
      it plays a critical role in facilitating rapid platelet activation, which is
      essential for stable thrombus formation.

PMID- 24888522
TI  - In vivo imaging of mouse tumors by a lipidated cathepsin S substrate.
AB  - The synthesis and evaluation of two cathepsin S-specific probes is described. For
      long-term retention of the probe at the target site and a high signal-to-noise
      ratio, we introduced a lipidation approach via the simple attachment of palmitoic
      acid to the reporter. After cathepsin S-specific cleavage in cultured cells and
      in a grafted tumor mouse model, fluorescence increased owing to dequenching and
      we observed an intracellular accumulation of the fluorescence in the target
      tissue. The lipidated probe provided a prolonged and strongly fluorescent signal
      in tumors when compared to the very similar non-lipidated probe, demonstrating
      that non-invasive tumor identification is feasable. The homing principle by probe
      lipidation might also work for selective administration of cytotoxic compounds to
      specifically reduce tumor mass. 

PMID- 24888523
TI  - Simple snoring: not quite so simple after all?
AB  - Simple snoring (SS), in the absence of obstructive sleep apnoea (OSA), is a
      common problem, yet our understanding of its causes and consequences is
      incomplete. Our understanding is blurred by the lack of consistency in the
      definition of snoring, methods of assessment, and degree of concomitant
      complaints. Further, it remains contentious whether SS is independently
      associated with daytime sleepiness, or adverse health outcomes including
      cardiovascular disease and metabolic syndrome. Regardless of this lack of
      clarity, it is likely that SS exists on one end of a continuum, with OSA at its
      polar end. This possibility highlights the necessity of considering an otherwise
      'annoying' complaint, as a serious risk factor for the development and
      progression of sleep apnoea, and consequent poor health outcomes. In this review,
      we: 1) highlight variation in prevalence estimates of snoring; 2) review the
      literature surrounding the distinctions between SS, upper airway resistance
      syndrome (UARS) and OSA; 3) present the risk factors for SS, in as far as it is
      distinguishable from UARS and OSA; and 4) describe common correlates of snoring,
      including cardiovascular disease, metabolic syndrome, and daytime sleepiness. 

PMID- 24888525
TI  - Altered medial prefrontal activity during dynamic face processing in
      schizophrenia spectrum patients.
AB  - BACKGROUND: Processing the emotional content of faces is recognised as a key
      deficit of schizophrenia, associated with poorer functional outcomes and possibly
      contributing to the severity of clinical symptoms such as paranoia. At the neural
      level, fMRI studies have reported altered limbic activity in response to facial
      stimuli. However, previous studies may be limited by the use of cognitively
      demanding tasks and static facial stimuli. To address these issues, the current
      study used a face processing task involving both passive face viewing and dynamic
      social stimuli. Such a task may (1) lack the potentially confounding effects of
      high cognitive demands and (2) show higher ecological validity. METHODS:
      Functional MRI was used to examine neural activity in 25 patients with a DSM-IV
      diagnosis of schizophrenia/schizoaffective disorder and 21 age- and gender
      matched healthy controls while they participated in a face processing task, which
      involved viewing videos of angry and neutral facial expressions, and a non
      biological baseline condition. RESULTS: While viewing faces, patients showed
      significantly weaker deactivation of the medial prefrontal cortex, including the
      anterior cingulate, and decreased activation in the left cerebellum, compared to
      controls. Patients also showed weaker medial prefrontal deactivation while
      viewing the angry faces relative to baseline. DISCUSSION: Given that the anterior
      cingulate plays a role in processing negative emotion, weaker deactivation of
      this region in patients while viewing faces may contribute to an increased
      perception of social threat. Future studies examining the neurobiology of social
      cognition in schizophrenia using fMRI may help establish targets for treatment
      interventions.

PMID- 24888524
TI  - A fundamental role for hippocampal parvalbumin in the dopamine hyperfunction
      associated with schizophrenia.
AB  - Postmortem studies in schizophrenia patients have demonstrated robust alterations
      in GABAergic markers throughout the neuraxis. It has been suggested that these
      alterations are restricted to subpopulations of interneurons, such as those
      containing the calcium binding protein parvalbumin. Indeed, a reduction in
      parvalbumin expression is a consistent observation in human postmortem studies,
      as well as, in a wide and diverse variety of animal models. However, it still
      remains to be determined whether this decrease in parvalbumin expression
      contributes to, or is a consequence of the disease. Here we utilize lentiviral
      delivered shRNA and demonstrate that a selective reduction in parvalbumin mRNA
      expression induces hyperactivity within the ventral hippocampus. In addition, we
      observe downstream increases in dopamine neuron population activity without
      changes in average firing rate or percent burst firing. These changes in dopamine
      neuron activity were associated with an enhanced locomotor response to
      amphetamine administration. These data therefore demonstrate that a reduction in
      ventral hippocampal parvalbumin expression is sufficient, in and of itself, to
      induce an augmented dopamine system function and behavioral hyper-responsivity to
      amphetamine, implicating a potential key role for parvalbumin in the
      pathophysiology of schizophrenia. 

PMID- 24888527
TI  - Second-generation antipsychotics and bone turnover in schizophrenia.
AB  - Accumulating evidence suggests that patients with schizophrenia are exposed to a
      high risk of osteoporosis/osteopenia caused by long-term antipsychotic treatment.
      The degree of bone mineral density (BMD) loss that a given antipsychotic may
      cause is not known. Examinations using a bone turnover marker may more accurately
      predict the ongoing bone states in psychiatric patients. We measured prolactin,
      estradiol, testosterone, and bone resorption marker (TRACP-5b) levels in 167
      patients with schizophrenia and 60 normal controls. The patients showed
      significantly higher levels of prolactin and lower levels of TRACP-5b compared to
      the controls. Moreover, prolactin was negatively correlated with estradiol and
      testosterone in the group of all male subjects and the male patients. TRACP-5b
      was positively correlated with prolactin in the female patients and negatively
      correlated with estradiol in the group of all female subjects. The results show
      that the bone resorption rate was rather attenuated in the patients compared to
      the normal controls, suggesting a complicated etiology of BMD loss in
      schizophrenia patients. Several meaningful correlations between key factors in
      this study confirmed that hyperprolactinemia induced the suppression of sex
      hormones, and possibly led to the higher bone turnover. These results indicate
      that measurement of the resorption marker TRACP-5b might be useful to clarify the
      pathology of BMD loss. 

PMID- 24888528
TI  - Radiographic evaluation of the elbow.
AB  - Despite a number of advanced imaging modalities, plain film x-ray is essential
      for diagnostic evaluation of the elbow. Although computed tomography and magnetic
      resonance imaging continue to provide many uses in subtle processes or advanced
      evaluation, x-rays should typically provide initial, and often all, necessary
      imaging. Plain film imaging is used to evaluate trauma including fractures and
      dislocations, occult or suspected bony injury, instability patterns, tumor,
      arthritis and degenerative disease, and causes of associated pathology such as
      compression neuropathy. 

PMID- 24888529
TI  - International Federation of Societies for Surgery of the Hand 2013 Committee's
      report on wrist dart-throwing motion.
AB  - This report updates information on wrist dart-throwing (DT) motion, based on the
      most recent research published on the kinematics, kinetics, and clinical
      applications of DT motion. A wide range of DT planes exists. "Pure" DT motion is
      done along an oblique plane that intercepts the coronal and sagittal planes at
      the zero position, and occurs almost exclusively at the midcarpal joint with near
      zero scaphoid and lunate motion. "Functional" DT motion such as a hammering is
      done along an oblique plane that is almost parallel to the pure DT plane, but
      that has an offset toward the dorsal side. Functional DT rotation has greater
      scaphoid and lunate motion compared with pure DT motion. Midcarpal arthrodesis
      adversely affects DT motion compared with radiocarpal arthrodesis. During a DT
      motion, the mean and peak tendon forces of the flexor carpi ulnaris and the
      extensor carpi radialis longus were the greatest among wrist motors. By
      performing a task along the plane of DT motion, the scapholunate (SL) joint was
      stable and SL ligament elongation was minimal in healthy subjects. However, a
      more recent study of patients with SL dissociation revealed that DT exercises
      applied tensile forces on the SL ligament and induced an SL gap. 

PMID- 24888526
TI  - Cognitive functioning in first-episode schizophrenia: MATRICS Consensus Cognitive
      Battery (MCCB) Profile of Impairment.
AB  - BACKGROUND: Although many studies have assessed cognitive functioning in first
      episode schizophrenia (FESz), the pattern and severity of impairment across
      cognitive domains remain unclear. Moreover, few studies have directly compared
      the pattern of cognitive performance between FESz and chronic schizophrenia
      (CSz). In this study we examined the cognitive impairment profile in FESz using a
      standardized neurocognitive battery (MATRICS Consensus Cognitive Battery; MCCB).
      METHODS: MCCB data were compared from 105 FESz patients, 176 CSz patients and 300
      non-psychiatric (NP) participants. Mixed model analysis evaluated group
      differences in MCCB profiles and relative strengths and weaknesses in the MCCB
      profiles of patients. Clinical implications of MCCB performance were also
      examined; we compared the proportion of participants from each group who
      exhibited clinically-significant global cognitive impairment based on the MCCB
      Overall Composite score. RESULTS: FESz and CSz showed impaired performance across
      all MCCB domains relative to NP. With the exception of relative preservation of
      working memory and social cognition in FESz, the MCCB domain scores were similar
      in FESz and CSz. The distribution of impairment on the Overall Composite score
      did not significantly differ between FESz and CSz; compared to NP, both patient
      groups were overrepresented in moderate and severe impairment categories.
      CONCLUSION: The pattern, magnitude, and distribution of severity of impairment in
      FESz were similar to that observed in CSz. However, early in the illness, there
      may be relative sparing of working memory and social cognition.

PMID- 24888530
TI  - All-solid-state Z-scheme photocatalytic systems.
AB  - The current rapid industrial development causes the serious energy and
      environmental crises. Photocatalyts provide a potential strategy to solve these
      problems because these materials not only can directly convert solar energy into
      usable or storable energy resources but also can decompose organic pollutants
      under solar-light irradiation. However, the aforementioned applications require
      photocatalysts with a wide absorption range, long-term stability, high charge
      separation efficiency and strong redox ability. Unfortunately, it is often
      difficult for a single-component photocatalyst to simultaneously fulfill all
      these requirements. The artificial heterogeneous Z-scheme photocatalytic systems,
      mimicking the natural photosynthesis process, overcome the drawbacks of single
      component photocatalysts and satisfy those aforementioned requirements. Such
      multi-task systems have been extensively investigated in the past decade.
      Especially, the all-solid-state Z-scheme photocatalytic systems without redox
      pair have been widely used in the water splitting, solar cells, degradation of
      pollutants and CO2 conversion, which have a huge potential to solve the current
      energy and environmental crises facing the modern industrial development. Thus,
      this review gives a concise overview of the all-solid-state Z-scheme
      photocatalytic systems, including their composition, construction, optimization
      and applications. 

PMID- 24888531
TI  - Abstracts of the 28th EFI European Immunogenetics and Histocompatibility
      Conference, June 25th-28th, 2014, Stockholm, Sweden.

PMID- 24888532
TI  - Outcome stagnation of liver transplantation for primary sclerosing cholangitis in
      the Model for End-Stage Liver Disease era.
AB  - PURPOSE: Survival after liver transplantation (LTX) has decreased in Germany
      since the implementation of Model for end-stage liver disease (MELD)-based liver
      allocation. Primary sclerosing cholangitis (PSC) is known for its otherwise
      excellent outcome after LTX. The influence of MELD-based liver allocation and
      subsequent allocation policy alterations on the outcome of LTX for PSC is
      analyzed. METHODS: This is a retrospective observational study including 126
      consecutive patients treated with LTX for PSC between January 1, 1999 and August
      31, 2012. The PSC cohort was further compared to all other indications for LTX in
      the study period (n=1420) with a mean follow-up of 7.9 years (SD 3.2).
      Multivariate risk-adjusted analyses were performed. Alterations of allocation
      policy have been taken into account systematically. RESULTS: Transplant
      recipients suffering from PSC are significantly younger (p<0.001), can be
      discharged earlier (p=0.018), and have lower 3-month mortality than patients with
      other indications (p=0.044). The observed time on the waiting list is
      significantly longer for patients with PSC (p<0.001), and there is a trend toward
      lower match MELD points in the PSC cohort (p=0.052). No improvement in means of
      short-term mortality could be shown in relation to alterations of allocation
      policy within the MELD era (p=0.375). Survival rates of the pre-MELD era did not
      differ significantly from those of the MELD era (p=0.097) in multivariate risk
      adjusted analysis. Patients in the MELD era suffered pre-transplant significantly
      more frequently from dominant bile duct stenosis (p=0.071, p=0.059, p=0.048,
      respectively; chi2). CONCLUSIONS: Progress is stagnating in LTX for PSC. Current
      liver allocation for PSC patients should be reconsidered.

PMID- 24888533
TI  - Differential regulation of crossed cutaneous effects on the soleus H-reflex
      during standing and walking in humans.
AB  - Although sensory inputs from the contralateral limb strongly modify the amplitude
      of the Hoffmann (H-) reflex in a static posture, it remains unknown how these
      inputs affect the excitability of the monosynaptic H-reflex during walking. Here,
      we investigated the effect of the electrical stimulation of a cutaneous (CUT)
      nerve innervating the skin on the dorsum of the contralateral foot on the
      excitability of the soleus H-reflex during standing and walking. The soleus H
      reflex was conditioned by non-noxious electrical stimulation of the superficial
      peroneal nerve in the contralateral foot. Significant crossed facilitation of the
      soleus H-reflex was observed at conditioning-to-test intervals in a range of 100
      130 ms while standing, without any change in the background soleus
      electromyographic (EMG) activity. In contrast, the amplitude of the soleus H
      reflex was significantly suppressed by the contralateral CUT stimulation in the
      early-stance phase of walking. The background EMG activity of the soleus muscle
      was equivalent between standing and walking tasks and was unaffected by CUT
      stimulation alone. These findings suggest that the crossed CUT volleys can affect
      the presynaptic inhibition of the soleus Ia afferents and differentially modulate
      the excitability of the soleus H-reflex in a task-dependent manner during
      standing and walking.

PMID- 24888534
TI  - Crawling and walking infants encounter objects differently in a multi-target
      environment.
AB  - From birth, infants move their bodies in order to obtain information and
      stimulation from their environment. Exploratory movements are important for the
      development of an infant's understanding of the world and are well established as
      being key to cognitive advances. Newly acquired motor skills increase the
      potential actions available to the infant. However, the way that infants employ
      potential actions in environments with multiple potential targets is undescribed.
      The current work investigated the target object selections of infants across a
      range of self-produced locomotor experience (11- to 14-month-old crawlers and
      walkers). Infants repeatedly accessed objects among pairs of objects differing in
      both distance and preference status, some requiring locomotion. Overall, their
      object actions were found to be sensitive to object preference status; however,
      the role of object distance in shaping object encounters was moderated by
      movement status. Crawlers' actions appeared opportunistic and were biased towards
      nearby objects while walkers' actions appeared intentional and were independent
      of object position. Moreover, walkers' movements favoured preferred objects more
      strongly for children with higher levels of self-produced locomotion experience.
      The multi-target experimental situation used in this work parallels conditions
      faced by foraging organisms, and infants' behaviours were discussed with respect
      to optimal foraging theory. There is a complex interplay between infants' agency,
      locomotor experience, and environment in shaping their motor actions. Infants'
      movements, in turn, determine the information and experiences offered to infants
      by their micro-environment.

PMID- 24888535
TI  - Grasp: combined contribution of object properties and task constraints on hand
      and finger posture.
AB  - We compared the effect of different object properties on human upper-limb posture
      during reach-to-grasp tasks. A combination of extrinsic (object position),
      intrinsic (object type) and contextual object properties (grasp type) was
      investigated. Three-dimensional reach posture was measured by the hand position
      and orientation relative to the object at the time of stable object contact (with
      the digits). Similarly, the grasp posture was quantified by the angular digit
      configuration at the time of stationary object contact. We found that hand
      position and hand orientation were not only dependent on object position, as
      previously hypothesized, but also on object type and grasp type. Similarly,
      angular digit configuration was also dependent on extrinsic and contextual
      properties, and not only on object type (the intrinsic property). Principal
      component analysis revealed that two principal components (PCs) explained >79 %
      of the variation in the reach posture, whereas four PCs explained >76 % of the
      variation of the grasp posture. Again, PCs represented combinations of the input
      variables, i.e., there was no clear separation between the extrinsic variable
      acting specifically on the reach component, and the intrinsic variable on the
      grasp component. Contrary to the Dual Visuomotor Channel theory, these results
      suggest that extrinsic, intrinsic and contextual object variables do not act
      separately and exclusively on the neural control of the reach component or on
      that of the grasp component, but interact on both.

PMID- 24888537
TI  - Echocardiography for patent ductus arteriosus including closure in adults.
AB  - Patent ductus arteriosus (PDA) represents at least 5-10% of all congenital heart
      defects (CHDs) making it a very important commonly diagnosed lesion. Although
      spontaneous closure of the PDA occurs within 24 to 48 hours after birth in the
      majority, those children who do not have natural or surgical closure may have a
      persistent PDA into adulthood. The diagnosis is most often confirmed by
      echocardiography that also guides catheter-based interventions and surgeries.
      Echocardiography continues to be the most important tool in long-term follow-up
      of residua and sequelae. 

PMID- 24888538
TI  - Does stapled anopexy for bleeding haemorrhoids cure associated anaemia?
AB  - AIM: The aim of this study was to evaluate the effectiveness of stapled anopexy
      (SA) in patients with chronic bleeding haemorrhoids and secondary anaemia.
      METHOD: Our department performed 340 SA procedure per patient for haemorrhoids
      between January 1999 and December 2011. Fifty (14.7%) of these patients (25 male
      patients and 25 female patients) had anaemia (haemoglobin concentration < 13 g/dl
      in male patients and < 12 g/dl in female patients) secondary to chronic
      haemorrhoidal bleeding. Patients with colorectal bleeding and anaemia not caused
      by haemorrhoids were excluded. The mean (SD) age was 56.4 (13.9) years and the
      mean (SD) haemoglobin concentration was 9.2 (1.6) g/dl for male patients and 10.4
      (1.2) g/dl for female patients. Five (10%) patients with anaemia had Grade II, 22
      (44%) had Grade III and 23 (46%) had Grade IV haemorrhoids. The median (range)
      duration of postoperative follow-up was six (1-12) years. RESULTS: None of the
      patients required early postoperative admission or experienced early or late
      complications related to SA. The procedure was successful (normal haemoglobin
      concentration and no bleeding at 6 months postsurgery) in 45 (90%) patients. Of
      the five (10%) patients in whom SA was ineffective, one had Grade II, three had
      Grade III and one had Grade IV haemorrhoids. All these patients underwent
      Milligan-Morgan haemorrhoidectomy 3 months after SA. CONCLUSION: SA is an
      effective treatment for patients with bleeding haemorrhoids and subsequent
      anaemia. In our experience, the success rate was satisfactory and there were no
      serious complications.

PMID- 24888539
TI  - A pair of homoeolog ClpP5 genes underlies a virescent yellow-like mutant and its
      modifier in maize.
AB  - Gene-background interaction is a commonly observed phenomenon in many species,
      but the molecular mechanisms of such an interaction is less well understood. Here
      we report the cloning of a maize mutant gene and its modifier. A recessive mutant
      with a virescent yellow-like (vyl) phenotype was identified in an ethyl
      methanesulfonate-mutagenized population derived from the maize inbred line B73.
      Homozygous mutant maize plants exhibited a yellow leaf phenotype after emergence
      but gradually recovered and became indistinguishable from wild-type plants after
      approximately 2 weeks. Taking the positional cloning approach, the Chr.9_ClpP5
      gene, one of the proteolytic subunits of the chloroplast Clp protease complex,
      was identified and validated as the candidate gene for vyl. When introgressed by
      backcross into the maize inbred line PH09B, the mutant phenotype of vyl lasted
      much longer in the greenhouse and was lethal in the field, implying the presence
      of a modifier(s) for vyl. A major modifier locus was identified on chromosome 1,
      and a paralogous ClpP5 gene was isolated and confirmed as the candidate for the
      vyl-modifier. Expression of Chr.1_ClpP5 is induced significantly in B73 by the
      vyl mutation, while the expression of Chr.1_ClpP5 in PH09B is not responsive to
      the vyl mutation. Moreover, expression and sequence analysis suggests that the
      PH09B Chr.1_ClpP5 allele is functionally weaker than the B73 allele. We propose
      that functional redundancy between duplicated paralogous genes is the molecular
      mechanism for the interaction between vyl and its modifier.

PMID- 24888536
TI  - Implied motion perception from a still image in infancy.
AB  - Visual motion perception can arise from non-directional visual stimuli, such as
      still images (implied motion, cf. Kourtzi, Trends Cogn Sci 8:47-49, 2004). We
      tested 5- to 8-month-old infants' implied motion perception with two experiments
      using the forced-choice preferential looking method. Our results indicated that a
      still image of a person running toward either the left or right side
      significantly enhanced infants' visual preference for a visual target that
      consistently appeared on the same side as the running direction (the run
      condition in Experiment 1). Such enhanced visual preference disappeared in
      response to an image of the same person standing and facing the left/right side
      (the stand condition in Experiment 1), an image of the running figure covered
      with a set of opaque rectangles (the block condition in Experiment 2) (Gervais et
      al. in Atten Percept Psychophys 72:1437-1443, 2010), and an image of the inverted
      running figure (the inversion condition in Experiment 3). These results suggest
      that only the figure that implied dynamic body motion shifted the infants' visual
      preference to the same direction as the implied running action. These findings
      demonstrate that even infants as young as 5 to 8 months old are sensitive to the
      implied motion of static figures.

PMID- 24888540
TI  - Home-use icterometry in neonatal hyperbilirubinaemia: Cluster-randomised
      controlled trial in Vietnam.
AB  - AIM: To determine whether home-use icterometry improves parental recognition of
      neonatal jaundice, early care seeking and treatment to minimize risks of
      bilirubin encephalopathy. METHODS: Cluster-randomised controlled trial of
      community-level icterometry used at home by mothers in Chi Linh, Vietnam. Rural
      health-care workers identified and enrolled term newborns. Post-partum mothers
      received jaundice education and icterometry instructions and were cluster
      randomised by commune. Cases received icterometers (icterometer group (IG)) and
      controls did not (control group (CG)). Subjects received mobile telephone calls
      from post-natal days 2-7 to determine maternal recognition by visual inspection
      and icterometer detection of jaundice (>= 3.0 on five-point scale). Mothers
      without telephones, premature newborns (<35 weeks) or newborns hospitalised >5
      days were excluded. RESULTS: Three hundred fifty-two subjects were enrolled (183
      IG and 169 CG), of whom 11 (3.4%) were lost to telephone follow-up. Jaundice was
      recognised and/or detected in 94 (27%) of all newborns. Icterometry helped 11
      mothers (6%) detect neonatal jaundice that was not visually recognised by IG
      mothers. Detection by IG mothers was not statistically greater than CG mothers (P
      = 0.09). Follow-up care seeking was 8% in both groups (P = 0.2), and 11% of
      jaundiced newborns received treatment (9% IG vs. 16% CG, P = 0.3). Newborns who
      received care had bilirubin measurements that averaged 257 MUmol/L IG vs. 322
      MUmol/L CG (P = 0.3). There were no deaths. CONCLUSIONS: In this pilot study,
      home-use icterometry may help improve parental detection of jaundice in rural
      Vietnam. However, larger studies are necessary to determine the changes in
      recognition, care seeking and treatment.

PMID- 24888541
TI  - Stigma, deviance and morality in young adults' accounts of inflammatory bowel
      disease.
AB  - For young adults with inflammatory bowel disease (IBD), perceived stigma has been
      found to be a salient concern. Drawing on interviews with individuals with IBD
      aged 18-29 (n = 16), this article uses rhetorical discourse analysis to explore
      how stigma is discursively constructed by young adults, with a focus on the moral
      underpinnings of the participants' talk. Their representations showed both felt
      stigma and enacted stigma; principally related to the perceived taboo surrounding
      the symptoms of their condition, which often led to the non-disclosure or
      concealment of the condition. The different ways in which stigma is manifested in
      the accounts present a challenge to recent arguments questioning the relevance of
      this concept in chronic illness research, though it was found that it is not
      adequate to look at stigma alone and, given the unstable nature of IBD,
      negotiating stigma in relation to possible charges of deviance is a pertinent
      issue for these young adults. For instance, non-disclosure because of shame could
      result in individuals experiencing blame. Accounts were constructed through a
      range of discursive strategies, allowing the participants to present themselves
      in morally appropriate ways throughout. Suggestions are made about future
      directions in addressing stigma and deviance in relation to this cohort. 

PMID- 24888542
TI  - The force-velocity relationship at negative loads (assisted shortening) studied
      in isolated, intact muscle fibres of the frog.
AB  - AIM: The study was undertaken to explore the force-velocity relationship under
      conditions where the myofilament system is subjected to an external force that
      serves as a negative load and assists the shortening movement. METHODS: The
      experiments were carried out on single muscle fibres isolated from the anterior
      tibialis muscle of Rana temporaria. The fibres, being operated under load-clamp
      control, were released to shorten during tetanic stimulation at sarcomere lengths
      where the fibres carried different degrees of passive tension. The shortening
      thus occurred while the sarcomeres were subjected to a force that may be
      characterized as a 'negative load', that is, a force assisting the shortening
      movement. RESULTS: The force-velocity relationship below zero load was found to
      be a smooth continuation of the force-velocity curve recorded at positive loads
      with the shortening velocity increasing steeply at loads below zero. A negative
      load amounting to merely 10% of the isometric force, thus raised the shortening
      velocity to a level two to three times higher than V0 , the velocity recorded at
      zero load. CONCLUSIONS: The results provide evidence that, even in the presence
      of a longitudinal compressive force, the speed of shortening of the muscle fibre
      is determined by the cycling rate of the interacting cross-bridges. The force
      velocity relationship at negative loads may play a relevant part during fast
      movements of striated muscle as pointed out in the discussion.

PMID- 24888544
TI  - Rhodium-catalyzed stereoselective amination of thioethers with N
      mesyloxycarbamates: DMAP and bis(DMAP)CH(2)Cl(2) as key additives.
AB  - A stereoselective Rh-catalyzed intermolecular amination of thioethers using a
      readily available chiral N-mesyloxycarbamate to produce sulfilimines in excellent
      yields and diastereomeric ratio is described. A catalytic mixture of 4
      dimethylaminopyridine (DMAP) and bis(DMAP)CH2 Cl2 proved pivotal in achieving
      high selectivity. The X-ray crystal structure of the (DMAP)2 ?[Rh2 {(S)-nttl}4 ]
      complex was obtained and mechanistic studies suggested a Rh(II) -Rh(III) complex
      as the catalytically active species. 

PMID- 24888543
TI  - Usefulness of SWI for the Detection of Iron in the Motor Cortex in Amyotrophic
      Lateral Sclerosis.
AB  - PURPOSE: The purpose of the present retrospective study was to evaluate the
      sensitivity of susceptibility-weighted imaging (SWI) compared to conventional
      spin-echo T2-weighted and T2*-weighted images in detecting iron deposition in the
      motor cortex of amyotrophic lateral sclerosis (ALS) patients in comparison with
      age-matched normal controls. We also investigated the etiology of the low signal
      referring to the pathology of one autopsy case. METHODS: This retrospective
      magnetic resonance (MR) study included 23 ALS patients and 28 age-matched normal
      controls. The signal intensity of the motor cortex was scored by SWI,
      conventional T2-weighted images and T2*-weighted images. A postmortem study of
      one patient was also performed. RESULTS: On SWI, there was a significant
      difference between the precentral cortical signal intensity scores in the ALS
      patients and the controls (P < .0001). The total scores of signal intensities of
      the precentral cortex were positively correlated with age in the normal controls
      (r = .494), but no correlation was observed in the ALS patients. The postmortem
      study showed intensely stained microglias and macrophages after antiferritin
      antibody staining in the precentral cortices. CONCLUSIONS: Decreased signal
      intensity of the motor cortex on SWI may serve a useful role in ALS diagnoses,
      particularly in young patients. MR images were also helpful for speculating on
      the etiology of ALS.

PMID- 24888545
TI  - Neonatal lupus erythematosus: the use of telephone images in diagnosis.

PMID- 24888547
TI  - Regulating the interactions of adsorbates on surfaces by scanning tunneling
      microscopy manipulation.
AB  - Scanning tunneling microscopy (STM) manipulation has received wide attention in
      the surface science community since the pioneering work of Eigler to construct
      surface nanostructures in an atom by atom fashion. Lots of scientists have been
      inspired and devoted to study the surface issues with the help of STM
      manipulations and great achievements have been obtained. In this Minireview, we
      mainly describe the recent progress in applying STM manipulations to regulate the
      inter-adsorbate and adsorbate-substrate interactions on solid surfaces. It was
      shown that this technique could not only differentiate intermolecular
      interactions but also construct molecular nanostructures by regulating different
      kinds of inter-adsorbate interactions or adsorbate-substrate interactions. 

PMID- 24888546
TI  - The molecular and cellular effects of ageing on the periodontal ligament.
AB  - AIM: Many in vitro studies have investigated age-related biological changes in
      cells comprising the periodontium but the basic question of whether the
      periodontium can maintain its integrity with age remains unanswered. Thus, the
      aim of this study was to understand how, in the absence of disease, advancing age
      impacts the structure of the periodontium. MATERIALS AND METHODS: Of 4, 10, 25,
      and 50-week-old mice were examined using histology and immunohistochemical
      analyses for cell proliferation, cell turnover, collagen quantity and quality,
      osteogenic markers, bone turnover, and cytokine expression. RESULTS: The
      periodontal ligament (PDL) space shows a gradual decrease in width over the
      lifespan of the mice. Cell proliferation as well as the quantity and quality of
      collagen fibres decreased with age although cell density did not appear to be
      altered. Osteoprogenitor markers in the PDL maintained their expression with
      increasing age. Alkaline phosphatase (ALP) activity decreased, but osteoclast
      activity increased with age. CONCLUSIONS: Ageing is associated with a decline in
      the quality and quantity of collagen and an increase in bone resorption, all of
      which can diminish the function of the periodontium even in the absence of
      disease.

PMID- 24888548
TI  - Challenges in universal coverage and utilization of insecticide-treated bed nets
      in migrant plantation workers in Myanmar.
AB  - BACKGROUND: High coverage of the bed nets can reduce mortality and morbidity of
      mosquito-borne diseases including malaria. Although the migrant workers are at
      high risk of malaria, there are many hidden challenges in universal coverage and
      utilization of the insecticide-treated nets (ITNs) in this populations. METHODS:
      Cross sectional study was conducted in 170 migrant workers in palm oil plantation
      sites in Tanintharyi Region and 175 in rubber plantation sites in Mon State. A
      multistage stratified cluster sampling was applied to select the participants.
      During household visit, face-to-face interviews using structured pre-coded, pre
      tested questionnaires and direct observation on installation of the bed nets was
      conducted. Two focus group discussions in each site were done by sample
      stratified purposive sampling method mainly focused on effective utilization of
      bed nets. RESULTS: Among them, 332 (96.2%) had a bed net and 284 (82.3%) had an
      ITN, while 204 (59.1%) had unused extranets. Among the ITNs users, 28.9% reported
      problems including insecticide smell (56.9%), dizziness (20.2%), headache (12.8%)
      and itchiness (9.2%). More than 75% received ITNs from health authorities and
      NGOs free-of-charge. More than 70% wanted to buy a net but they were unaffordable
      for 64% of them. On observation, only five families could show no bed net, but
      80% showed 1-3 ITNs. Consistent utilization in all seasons was noted in 189
      (53.1%), that was higher in palm oil plantation than rubber plantation workers (p
      = 0.0001) due to the nature of the work at night. Perceived malaria risk was also
      significantly higher ITNs consistent users than non-users (p = 0.0004) and better
      willingness to buy an ITN by themselves (p = 0.0005). They said that
      effectiveness of the ITNs was reduced after 6 months and 2-3 times washing. They
      wished to receive more durable smooth nets with small holes in lace. Misuses of
      the ITNs such as use the nets for animals and fishing, were also noted.
      CONCLUSION: There should be efforts to improve effective utilization of ITNs by
      continuous mass free distribution, durability monitoring, surveillance of
      insecticide resistance of the vector and behaviour change interventions in
      migrant plantation workers.

PMID- 24888549
TI  - Morphological similarities after compression trauma of bovine and human
      intervertebral discs: Do disc cells have a chance of surviving?
AB  - To study the behavior of bovine disc cells and changes in disc matrix following
      in vitro compression tests; to compare the findings to investigations on human
      intervertebral discs (IVD) after burst fracture of the cervical spine. Healthy
      IVDs (n = 21) from three bovine tails were studied at 6 and 12 h post-mortem,
      with 16 IVDs subjected to impact loading and five as unloaded controls. IVDs (n =
      8) from patients with burst fractures were compared to the bovine compression
      group. Specimens were studied macroscopically, histologically, and
      ultrastructurally for healthy cells, balloon cells, and disc cell death (DCD).
      Annulus ruptures were seen in both post-trauma groups, with radial ruptures being
      present histologically in all loaded bovine discs. Balloon cells were found in
      some human IVDs and were induced in vitro in bovine loaded discs within a
      distinct range of absorbed energy. There was a positive correlation between DCD
      and absorbed energy in all compartments of bovine discs. Both species showed
      similar patterns of DCD in the different compartments. This study was able to
      show similarities between both species in cell morphologies and matrix damage.
      The survival of the disc after substantial compression trauma thus seems to
      remain highly questionable.

PMID- 24888550
TI  - Postglacial climate changes and rise of three ecotypes of harbour porpoises,
      Phocoena phocoena, in western Palearctic waters.
AB  - Despite no obvious barriers to gene flow in the marine realm, environmental
      variation and ecological specializations can lead to genetic differentiation in
      highly mobile predators. Here, we investigated the genetic structure of the
      harbour porpoise over the entire species distribution range in western Palearctic
      waters. Combined analyses of 10 microsatellite loci and a 5085 base-pair portion
      of the mitochondrial genome revealed the existence of three ecotypes, equally
      divergent at the mitochondrial genome, distributed in the Black Sea (BS), the
      European continental shelf waters, and a previously overlooked ecotype in the
      upwelling zones of Iberia and Mauritania. Historical demographic inferences using
      approximate Bayesian computation (ABC) suggest that these ecotypes diverged
      during the last glacial maximum (c. 23-19 kilo-years ago, kyrbp). ABC supports
      the hypothesis that the BS and upwelling ecotypes share a more recent common
      ancestor (c. 14 kyrbp) than either does with the European continental shelf
      ecotype (c. 28 kyrbp), suggesting they probably descended from the extinct
      populations that once inhabited the Mediterranean during the glacial and post
      glacial period. We showed that the two Atlantic ecotypes established a narrow
      admixture zone in the Bay of Biscay during the last millennium, with highly
      asymmetric gene flow. This study highlights the impacts that climate change may
      have on the distribution and speciation process in pelagic predators and shows
      that allopatric divergence can occur in these highly mobile species and be a
      source of genetic diversity.

PMID- 24888552
TI  - Influence of bacterial cellulose (nata) on the physicochemical and sensory
      properties of frankfurter.
AB  - The physicochemical and sensory characteristics of pork frankfurters containing
      different levels (10% to 30%) of bacterial cellulose (nata) were evaluated.
      Emulsion stability of the raw meat batter decreased with the addition of nata.
      For nata-added treatments, increasing levels of nata in frankfurters resulted in
      decreased textural hardness and shear values. Sensory results indicated that N10
      and N20 had significantly higher firmness scores than N30 and control. However,
      juiciness score did not differ for all treatments. Incorporation of nata at lower
      levels (10% to 20%) did not have detrimental effects on the physicochemical,
      textural, sensory, and microbiological properties of regular-fat frankfurters.
      Addition of a higher level (30%) of nata essentially produced comparable sensory
      properties to the control, but lower levels of nata in frankfurters yielded
      higher sensory firmness and instrumental hardness values. Based on the composite
      results, manufacture of regular-fat frankfurter containing 10% to 20% high-fiber
      nata resulted in product quality comparable to the control. PRACTICAL
      APPLICATION: We demonstrated the manufacture of quality-improved frankfurters
      with the inclusion of a high-fiber functional ingredient, nata.

PMID- 24888553
TI  - Viruses exploit the function of epidermal growth factor receptor.
AB  - Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that
      regulates cellular homeostatic processes. Following ligand binding, EGFR
      activates different downstream signalling cascades that promote cell survival,
      proliferation, motility, and angiogenesis and induces F-actin-dependent EGFR
      endocytosis, which relocalises the activated receptors for degradation or
      recycling. The responses that are induced by ligand binding to EGFR, including
      cell signalling activation, protein kinase phosphorylation and cytoskeletal
      network rearrangement, resemble those induced by virus infection. Increasing
      evidence demonstrates that many viruses usurp EGFR endocytosis or EGFR-mediated
      signalling for entry, replication, inflammation, and viral antagonism to the host
      antiviral system. In addition, viruses have acquired sophisticated mechanisms to
      regulate EGFR functions by interrupting the EGFR-recycling process and modulating
      EGFR expression. In this review, we provide an overview of the mechanisms by
      which viruses alter EGFR signalling in favour of their continued survival.

PMID- 24888554
TI  - Uptake and metabolism of D-glucose in isolated acinar and ductal cells from rat
      submandibular glands.
AB  - The present study deals with the possible effects of selected environmental
      agents upon the uptake and metabolism of d-glucose in isolated acinar and ductal
      cells from the rat submandibular salivary gland. In acinar cells, the uptake of d
      [U-(14) C]glucose and its non-metabolised analogue 3-O-[(14) C-methyl]-d-glucose
      was not affected significantly by phloridzin (0.1 mM) or substitution of
      extracellular NaCl (115 mM) by an equimolar amount of CsCl, whilst cytochalasin B
      (20 MUM) decreased significantly such an uptake. In ductal cells, both phloridzin
      and cytochalasin B decreased the uptake of d-glucose and 3-O-methyl-d-glucose.
      Although the intracellular space was comparable in acinar and ductal cells, the
      catabolism of d-glucose (2.8 or 8.3 mM) was two to four times higher in ductal
      cells than in acinar cells. Phloridzin (0.1 mM), ouabain (1.0 mM) and
      cytochalasin B (20 MUM) all impaired d-glucose catabolism in ductal cells. Such
      was also the case in ductal cells incubated in the absence of extracellular
      Ca(2+) or in media in which NaCl was substituted by CsCl. It is proposed that the
      ductal cells in the rat submandibular gland are equipped with several systems
      mediating the insulin-sensitive, cytochalasin B-sensitive and phloridzin
      sensitive transport of d-glucose across the plasma membrane.

PMID- 24888555
TI  - How to more effectively lobby the legislative branch of government: report the
      extent of intellectual disability amongst a politician's constituents.
AB  - The use of national numbers and percentages to describe the millions of people
      with intellectual disabilities is beyond the comprehension of most people. The
      challenge is to personalize these numbers if we are to bring increased attention
      to these individuals. Examples of Census Bureau report data for the States,
      Congressional Districts, Counties, and High School districts are suggested as a
      format to lobby legislators with the realities of the numbers of their
      constituents who are affected by intellectual disabilities. 

PMID- 24888559
TI  - Planar-chiral through-space conjugated oligomers: synthesis and characterization
      of chiroptical properties.
AB  - Optically active through-space conjugated oligomers, namely, a dimer, trimer,
      tetramer, and cyclic trimer, consisting of a planar-chiral [2.2]paracyclophane
      skeleton were synthesized. In the ground state, observed similarities in the
      chiroptical properties of the oligomers were attributed to the equivalent
      orientations of two adjacent chromophores. In the excited state, the oligomers
      were folded into a form analogous to a one-handed helix by photoexcitation. All
      the compounds in dispersed solution exhibited intense circularly polarized
      luminescence with relatively large anisotropy factors on the order of 10(-3).

PMID- 24888558
TI  - The use of high pressure CO2 -facilitated pH swings to enhance in situ product
      recovery of butyric acid in a two-phase partitioning bioreactor.
AB  - Through the use of high partial pressures of CO2 (pCO2 ) to facilitate temporary
      pH reductions in two-phase partitioning bioreactors (TPPBs), improved pH
      dependent partitioning of butyric acid was observed which achieved in situ
      product recovery (ISPR), alleviating end-product inhibition (EPI) during the
      production of butyric acid by Clostridium tyrobutyricum (ATCC 25755). Through
      high pressure pCO2 studies, media buffering effects were shown to be
      substantially overcome at 60 bar pCO2 , resulting in effective extraction of the
      organic acid by the absorptive polymer Pebax(r) 2533, yielding a distribution
      coefficient (D) of 2.4 +/- 0.1 after 1 h of contact at this pressure.
      Importantly, it was also found that C. tyrobutyricum cultures were able to
      withstand 60 bar pCO2 for 1 h with no decrease in growth ability when returned to
      atmospheric pressure in batch reactors after several extraction cycles. A fed
      batch reactor with cyclic high pCO2 polymer extraction recovered 92 g of butyric
      acid to produce a total of 213 g compared to 121 g generated in a control
      reactor. This recovery reduced EPI in the TPPB, resulting in both higher
      productivity (0.65 vs. 0.33 g L(-1)  h(-1) ) and yield (0.54 vs. 0.40).
      Fortuitously, it was also found that repeated high pCO2 -facilitated polymer
      extractions of butyric acid during batch growth of C. tyrobutyricum lessened the
      need for pH control, and reduced base requirements by approximately 50%. Thus,
      high pCO2 -mediated absorptive polymer extraction presents a novel method for
      improving process performance in butyric acid fermentation, and this technique
      could be applied to the bioproduction of other organic acids as well.

PMID- 24888560
TI  - Water consumption in Iron Age, Roman, and Early Medieval Croatia.
AB  - Patterns of water consumption by past human populations are rarely considered,
      yet drinking behavior is socially mediated and access to water sources is often
      socially controlled. Oxygen isotope analysis of archeological human remains is
      commonly used to identify migrants in the archeological record, but it can also
      be used to consider water itself, as this technique documents water consumption
      rather than migration directly. Here, we report an oxygen isotope study of humans
      and animals from coastal regions of Croatia in the Iron Age, Roman, and Early
      Medieval periods. The results show that while faunal values have little
      diachronic variation, the human data vary through time, and there are wide ranges
      of values within each period. Our interpretation is that this is not solely a
      result of mobility, but that human behavior can and did lead to human oxygen
      isotope ratios that are different from that expected from consumption of local
      precipitation.

PMID- 24888562
TI  - Xylanolytic enzyme systems in Arthrobacter sp. MTCC 5214 and Lactobacillus sp.
AB  - The production of extracellular xylanolytic enzymes such as xylanase, alpha-l
      arabinofuranosidase (alpha-l-AFase), and acetyl xylan esterase (Axe) by marine
      Arthrobacter sp. and Lactobacillus sp. was investigated using different carbon
      sources. Induction and repression of all these enzymes differed with carbon
      source and also with the organism. Wheat bran was the best carbon source for the
      production of xylanase and alpha-l-AFase, whereas both isolates showed maximum
      Axe production when grown on oat bran as a carbon source. Preferential
      utilization of a carbon source for enzyme production can give us better insights
      into regulatory mechanism in these marine bacteria. Elution profile as well as
      zymogram analysis indicated the possibility of bifunctional alpha-l-AFase-Axes in
      both marine bacteria. 

PMID- 24888563
TI  - Timescales of emulsion formation caused by anisotropic particles.
AB  - Particle stabilized emulsions have received much interest in the recent past, but
      our understanding of the dynamics of emulsion formation is still limited. For
      simple spherical particles, the time dependent growth of fluid domains is
      dominated by the formation of droplets, particle adsorption and coalescence of
      droplets (Ostwald ripening), which eventually can be almost fully blocked due to
      the presence of the particles. Ellipsoidal particles are known to be more
      efficient stabilizers of fluid interfaces than spherical particles and their
      anisotropic shape and the related additional rotational degrees of freedom have
      an impact on the dynamics of emulsion formation. In this paper, we investigate
      this point by means of simple model systems consisting of a single ellipsoidal
      particle or a particle ensemble at a flat interface as well as a particle
      ensemble at a spherical interface. By applying combined multicomponent lattice
      Boltzmann and molecular dynamics simulations we demonstrate that the anisotropic
      shape of ellipsoidal particles causes two additional timescales to be of
      relevance in the dynamics of emulsion formation: a relatively short timescale can
      be attributed to the adsorption of single particles and the involved rotation of
      particles towards the interface. As soon as the interface is jammed, however,
      capillary interactions between the particles cause a local reordering on very
      long timescales leading to a continuous change in the interface configuration and
      increase of the interfacial area. This effect can be utilized to counteract the
      thermodynamic instability of particle stabilized emulsions and thus offers the
      possibility to produce emulsions with exceptional stability. 

PMID- 24888561
TI  - Distribution and diversity of Prochlorococcus ecotypes in the Red Sea.
AB  - Photosynthetic prokaryotes of the genus Prochlorococcus play a major role in
      global primary production in the world's oligotrophic oceans. A recent study on
      pelagic bacterioplankton communities in the northern and central Red Sea
      indicated that the predominant cyanobacterial 16S rRNA gene sequence types were
      from Prochlorococcus cells belonging to a high-light-adapted ecotype (HL II). In
      this study, we analyzed microdiversity of Prochlorococcus sp. at multiple depths
      within and below the euphotic zone in the northern, central, and southern regions
      of the Red Sea, as well as in surface waters in the same locations, but in a
      different season. Prochlorococcus dominated the communities in clone libraries of
      the amplified 16S-23S rRNA internal transcribed spacer (ITS) region. Almost no
      differences were found between samples from coastal or open-water sites, but a
      high diversity of Prochlorococcus ecotypes was detected at 100-meter depth in the
      water column. In addition, an unusual dominance of HL II-related sequences was
      observed in deeper waters. Our results indicate that the Red Sea harbors diverse
      Prochlorococcus lineages, but no novel ecotypes, despite its unusual
      physicochemical properties.

PMID- 24888565
TI  - A comparative study on the heparin-binding proteomes of Toxoplasma gondii and
      Plasmodium falciparum.
AB  - Toxoplasma gondii is an obligatory intracellular apicomplexan parasite which
      exploits host cell surface components in cell invasion and intracellular
      parasitization. Sulfated glycans such as heparin and heparan sulfate have been
      reported to inhibit cell invasion by T. gondii and other apicomplexan parasites
      such as Plasmodium falciparum. The aim of this study was to investigate the
      heparin-binding proteome of T. gondii. The parasite-derived components were
      affinity-purified on the heparin moiety followed by MS fingerprinting of the
      proteins. The heparin-binding proteins of T. gondii and P. falciparum were
      compared based on functionality and affinity to heparin. Among the proteins
      identified, the invasion-related parasite ligands derived from
      tachyzoite/merozoite surface and the secretory organelles were prominent.
      However, the profiles of the proteins were different in terms of affinity to
      heparin. In T. gondii, the proteins with highest affinity to heparin were the
      intracellular components with functions of parasite development contrasted to
      that of P. falciparum, of which the rhoptry-derived proteins were prominently
      identified. The profiling of the heparin-binding proteins of the two apicomplexan
      parasites not only explained the mechanism of heparin-mediated host cell invasion
      inhibition, but also, to a certain extent, revealed that the action of heparin on
      the parasite extended after endocytosis.

PMID- 24888564
TI  - Comparison of long non-coding RNAs, microRNAs and messenger RNAs involved in
      initiation and progression of esophageal squamous cell carcinoma.
AB  - Traditionally, cancer research has focused on protein-coding genes, which are
      considered the principal effectors and regulators of tumorigenesis. Non-coding
      RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have
      been widely reported to be important in the regulation of tumorigenesis and
      cancer development. However, to the best of our knowledge, investigation of the
      expression profiles of lncRNAs and a comparison of the involvement of lncRNAs,
      miRNAs and messenger RNAs (mRNAs) in esophageal tumorigenesis and development
      have not previously been performed. In the current study, intrinsic associations
      among the expression profiles of lncRNAs, miRNAs and mRNAs from normal esophageal
      tissues and those from cancer tissues were investigated. Oligonucleotide
      microarrays were used to detect the expression profiles of the three types of RNA
      in the canceration processes of human esophageal squamous cell carcinoma (ESCC)
      tissues. It was demonstrated that the different RNAs exhibit associated patterns
      of expression among normal esophageal epithelium, low-grade intraepithelial
      neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and carcinoma
      tissues, particularly in the critical period of canceration (HGIN to ESCC).
      Furthermore, the results indicated a high level of similarity in the potential
      function of lncRNAs, miRNAs and mRNAs in the processes of ESCC development. In
      the current study, a first generation atlas of lncRNA profiling and its
      association with miRNAs and mRNAs in the canceration processes of ESCC were
      presented. 

PMID- 24888566
TI  - Sexual function in the late postmenopause: a decade of follow-up in a population
      based cohort of Australian women.
AB  - INTRODUCTION: There is a paucity of longitudinal studies assessing sexual
      function of women in the late postmenopause. AIM: This study aims to describe
      sexual function of women in the late postmenopause and to investigate change from
      early postmenopause. METHODS: Cross-sectional analysis of 2012/13 and
      longitudinal analysis from 2002/04 of the population based, Australian cohort of
      the Women's Healthy Ageing Project, applying validated instruments: Short
      Personal Experience Questionnaire (SPEQ), Female Sexual Distress Scale (FSDS),
      Hospital Anxiety and Depression Scale, Geriatric Depression Scale, and California
      Verbal Learning Test. MAIN OUTCOME MEASURES: Sexual activity, SPEQ, and FSDS.
      RESULTS: Two hundred thirty women responded (follow-up rate 53%), mean age was 70
      years (range 64-77), 49.8% were sexually active. FSDS scores showed more distress
      for sexually active women (8.3 vs. 3.2, P<0.001). For 23 (23%) sexually active
      and for five (7%) inactive women, the diagnosis of female sexual dysfunction
      could be made. After adjustment, available partner (odds ratio [OR] 4.31,
      P<0.001), no history of depression (OR 0.49, P=0.036), moderate compared with no
      alcohol consumption (OR 2.43, P=0.019), and better cognitive function score
      (OR1.09, P=0.050) were significantly predictive for sexual activity. Compared
      with early postmenopause, 18% more women had ceased sexual activity. For women
      maintaining their sexual activity through to late postmenopause (n=82), SPEQ and
      FSDS scores had not changed significantly, but frequency of sexual activity had
      decreased (P=0.003) and partner difficulties had increased (P=0.043). [Correction
      added on 10 July 2014, after first online publication: Mean age of respondents
      was added.] CONCLUSIONS: In late postmenopause, half of the women were sexually
      active. Most important predictors were partner availability and no history of
      depression. However, being sexually active or having a partner were associated
      with higher levels of sexual distress. Compared with early postmenopause, sexual
      function scores had declined overall but were stable for women maintaining sexual
      activity. Further research into causes of sexual distress and reasons for sexual
      inactivity at this reproductive stage is warranted.

PMID- 24888567
TI  - The non-reverse transcriptase activity of the human telomerase reverse
      transcriptase promotes tumor progression (review).
AB  - In human cancer, high expression of telomerase is correlated with tumor
      aggressiveness and metastatic potential. Human telomerase reverse transcriptase
      (hTERT), which regulates telomere length, can promote tumor development. Most
      research on hTERT has been focused on its crucial function of telomere
      maintenance. However, there are many phenomena that cannot be explained by its
      reverse transcriptase activity. Accumulating evidence suggests that hTERT has
      functions independent of its protective function at the telomere ends, such as
      increasing the anti-apoptotic capacity of cells, enhancing DNA repair,
      maintaining stem cells and regulating gene expression. This review will provide
      an update on the non-reverse transcriptase activity of hTERT and its contribution
      to tumor formation, metastasis and cancer stem cell maintenance. Repression of
      the non-reverse transcriptase activity of hTERT may be a new strategy for tumor
      therapy.

PMID- 24888568
TI  - Iron, oxidative stress, and redox signaling in the cardiovascular system.
AB  - The redox state of the cell is predominantly dependent on an iron redox couple
      and is maintained within strict physiological limits. Iron is an essential metal
      for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and
      for cellular proliferation. The maintenance of stable iron concentrations
      requires the coordinated regulation of iron transport into plasma from dietary
      sources in the duodenum, from recycled senescent red cells in macrophages, and
      from storage in hepatocytes. The absorption of dietary iron, which is present in
      heme or nonheme form, is carried out by mature villus enterocytes of the duodenum
      and proximal jejunum. Multiple physiological processes are involved in
      maintaining iron homeostasis. These include its storage at the intracellular and
      extracellular level. Control of iron balance in the whole organism requires
      communication between sites of uptake, utilization, and storage. Key protein
      transporters and the molecules that regulate their activities have been
      identified. In this field, ferritins and hepcidin are the major regulator
      proteins. A variety of transcription factors may be activated depending on the
      level of oxidative stress, leading to the expression of different genes. Major
      preclinical and clinical trials have shown advances in iron-chelation therapy for
      the treatment of iron-overload disease as well as cardiovascular and chronic
      inflammatory diseases. 

PMID- 24888569
TI  - Response to "letter to the editor".

PMID- 24888570
TI  - Replication and cross-phenotype study based upon schizophrenia GWASs data in the
      Japanese population: support for association of MHC region with psychosis.
AB  - Recent genome-wide association studies (GWASs) of schizophrenia (SCZ) identified
      several susceptibility genes and suggested shared genetic components between SCZ
      and bipolar disorder (BD). We conducted a genetic association study of single
      nucleotide polymorphisms (SNPs) selected according to previous SCZ GWAS targeting
      psychotic disorders (SCZ and BD) in the Japanese population. Fifty-one SNPs were
      analyzed in a two-stage design using first-set screening samples (all SNPs: 1,032
      SCZ, 1,012 BD, and 993 controls) and second-set replication samples
      ("significant" SNPs in the first-set screening analysis: 1,808 SCZ, 821 BD, and
      2,321 controls). We assessed allelic associations between the selected SNPs and
      the three phenotypes (SCZ, BD, and "psychosis" [SCZ + BD]). Nine SNPs revealed
      nominal association signals for all comparisons (P(uncorrected) < 0.05), of which
      two SNPs located in the major histocompatibility complex region (rs7759855 in
      zinc finger and SCAN domain containing 31 [ZSCAN31] and rs1736913 in HLA-F
      antisense RNA1 [HLA-F-AS1]) were further assessed in the second-set replication
      samples. The associations were confirmed for rs7759855 (P(corrected) = 0.026 for
      psychosis; P(corrected) = 0.032 for SCZ), although the direction of effect was
      opposite to that in the original GWAS of the Chinese population. Finally, a meta
      analysis was conducted using our two samples and using our data and data from
      Psychiatric GWAS Consortium (PGC), which have shown the same direction of effect.
      SNP in ZSCAN31 (rs7759855) had the strongest association with the phenotypes
      (best P = 6.8 * 10(-5) for psychosis: present plus PGC results). These data
      support shared risk SNPs between SCZ and BD in the Japanese population and
      association between MHC and psychosis.

PMID- 24888571
TI  - A self-report measure of legal and administrative aggression within intimate
      relationships.
AB  - Although experts agree that intimate partner violence (IPV) is a multidimensional
      phenomenon comprised of both physical and non-physical acts, there is no measure
      of legal and administrative (LA) forms of IPV. LA aggression is when one partner
      manipulates the legal and other administrative systems to the detriment of
      his/her partner. Our measure was developed using the qualitative literature on
      male IPV victims' experiences. We tested the reliability and validity of our LA
      aggression measure on two samples of men: 611 men who sustained IPV and sought
      help, and 1,601 men in a population-based sample. Construct validity of the
      victimization scale was supported through factor analyses, correlations with
      other forms of IPV victimization, and comparisons of the rates of LA aggression
      between the two samples; reliability was established through Cronbach's alpha.
      Evidence for the validity and reliability of the perpetration scale was mixed and
      therefore needs further analyses and revisions before we can recommend its use in
      empirical work. There is initial support for the victimization scale as a valid
      and reliable measure of LA aggression victimization among men, but work is needed
      using women's victimization's experiences to establish reliability and validity
      of this measure for women. An LA aggression measure should be developed using
      LGBTQ victims' experiences, and for couples who are well into the divorce and
      child custody legal process. Legal personnel and practitioners should be educated
      on this form of IPV so that they can appropriately work with clients who have
      been victimized or perpetrate LA aggression.

PMID- 24888572
TI  - Myeloid dendritic cells are primed in allergic asthma for thymic stromal
      lymphopoietin-mediated induction of Th2 and Th9 responses.
AB  - BACKGROUND: Type 1 myeloid dendritic cells (mDCs) contribute to inception of
      allergic asthma (AA) and are regulated by epithelial-derived cytokines.
      OBJECTIVES: To evaluate whether mDCs from AA patients are primed for thymic
      stromal lymphopoietin (TSLP)-driven responses. METHODS: mDCs from 18 AA patients
      and 15 controls were purified using immunomagnetic sorting. Cells were pulsed
      with TSLP or Dermatophagoides pteronyssinus (Der p) allergen, before FACS
      phenotyping and co-culture with allogeneic CD4+ T cells. Bronchial biopsies from
      15 AA patients and four controls were immunostained for CD1c and TSLP receptor
      (TSLPR). RESULTS: Allergic asthma patients had a higher proportion of TSLPR+
      mDCs, in blood and bronchial mucosa. When compared to mDCs from controls, both
      TSLP- and Der p-pulsed blood mDCs from AA patients induced increased polarization
      of CD4+ T cells into Th2 cells (IL-5, IL-13, and GATA3+), while only TSLP-mDCs
      promoted Th9 cells (IL-9 and PU.1+ /IRF4+). In addition, OX40L was induced upon
      TSLP stimulation and was required for the induction of Th2, but not Th9, cells.
      In contrast, development of Th9 cells in this model depended on TGF-beta1.
      CONCLUSIONS: Our data indicate overlapping but partially distinct effects of TSLP
      and Der p allergen pathways, showing that DCs are primed in human asthma for TSLP
      driven induction of both Th2 and Th9 cells. This novel TSLP/mDC/Th9 axis operates
      through a distinct, OX40L-independent pathway. These data further highlight the
      TSLP pathway as a relevant target in human asthma.

PMID- 24888573
TI  - Human papillomavirus testing in young women: clinical outcomes of human
      papillomavirus triage in a UK cervical screening program.
AB  - BACKGROUND: In the United Kingdom, human papillomavirus (HPV) testing is used to
      triage women with borderline cytology or mild dyskaryosis; however, in young
      women, the value of triage is limited by the high HPV prevalence rate. The
      current study examined the impact of HPV triage on colposcopy referral,
      colposcopy procedures, and patient outcome in a cervical screening population
      that included women aged < 25 years. METHODS: Women aged 18 to 65 years attending
      for cervical screening in Northern Ireland were tested for HPV if their cytology
      result demonstrated borderline cytology or mild dyskaryosis. Of the 866 women
      eligible for HPV triage, those who tested negative for HPV were returned to
      routine screening and women who tested positive were referred to colposcopy.
      RESULTS: HPV prevalence was 82.07% in women aged < 25 years and 54.69% in women
      aged >= 25 years. Colposcopy referrals increased by 42.67%. The odds of
      undergoing a large loop excision of the transformation zone (LLETZ) compared with
      punch biopsy increased by 0.056 per year above the age of 31 years. LLETZ
      performed in women aged >= 25 years and those aged < 25 years yielded rates of
      cervical intraepithelial neoplasia of type 2 or higher (>= CIN2) of 57.04% and
      80.00%, respectively. The positive predictive value of HPV triage for detecting
      >= CIN2 was 29.92% in women aged < 25 years and 27.51% in the older age group.
      CONCLUSIONS: HPV triage substantially increased colposcopy referrals. The
      positive predictive value of a positive HPV test to detect >= CIN2 was not
      affected by age. LLETZ performed in women aged < 25 years yielded higher rates of
      >= CIN2 compared with the older age group.

PMID- 24888574
TI  - A multiscale model for simulating binding kinetics of proteins with flexible
      linkers.
AB  - The kinetics of protein interactions are essential determinants in many cellular
      processes such as signal transduction and transcriptional regulation. Many
      proteins involved in these functions contain intrinsic disordered regions. This
      makes conformational flexibility become an unneglectable factor when studying the
      binding kinetic of these proteins. Compared with the binding of rigid proteins
      that is limited by diffusions, the binding mechanisms of proteins with internal
      flexibility are much more complicated. Using a small protein that contains two
      domains and a connecting loop as a testing system, we developed a multiscale
      simulation framework to study the role of flexible linkers in regulating kinetics
      of protein binding. The association and dissociation processes were implemented
      by a coarse-grained Monte-Carlo algorithm, while the conformational changes of
      the flexible linker were captured from all-atom molecular dynamic simulations.
      Our simulations illustrated that the presence of the extended domain linker can
      enhance the rate of protein association. On the other hand, the full-length
      flexible molecule is more difficult to dissociate than its two rigid domains but
      much easier than the molecule with a rigid linker. Overall, our studies
      demonstrated that both kinetics and thermodynamics of protein binding are closely
      modulated by the dynamic features of linker regions.

PMID- 24888577
TI  - Ultraviolet-induced linear IgA bullous dermatosis: a case report and literature
      survey.

PMID- 24888578
TI  - A reagent for the one-step preparation of potassium acyltrifluoroborates (KATs)
      from aryl- and heteroarylhalides.
AB  - Potassium acyltrifluoroborates (KATs) are fascinating functional groups whose
      further exploration is limited by poor synthetic access. Documented herein is the
      design and synthesis of a new reagent for their one-step preparation from aryl-
      and heteroarylhalides. The reagent is a stable, soluble zwitterion prepared by S
      alkylation of a novel thioformamide trifluoroboronate. The KATs are prepared by
      adding one equivalent of nBuLi to a mixture of the aryl halide and the reagent at
      -78  degrees C. This protocol is suitable for the preparation of KATs containing
      pyridines, esters, nitro groups, and halides. 

PMID- 24888575
TI  - Decrease in clinical hypoglycemia in young children with type 1 diabetes treated
      with free-mixed aspart and detemir insulin: an open labeled randomized trial.
AB  - OBJECTIVE: To compare the effectiveness of a free-mix of aspart (A) and detemir
      (D) insulins (ADIM) with a commonly used premixed fixed-ratio aspart and neutral
      protamine Hagedorn (NPH) insulin mixture (ANIM) in young children with type 1
      diabetes (T1D) treated with twice-daily injections. The trial thus compares not
      only D vs. NPH, but also flexible, personalized insulin preparations vs. a fixed
      premixed preparation. RESEARCH DESIGN AND METHODS: This single-center, open
      label, randomized trial included 82 children with T1D. Patients stayed on ANIM
      for 1 yr of optimization of disease management, then were randomized to either
      ANIM (N = 41) or ADIM (N = 41) for another year. OUTCOMES: Frequency of severe or
      symptomatic episodes, glycated hemoglobin A1c (HbA1c), and blood glucose (BG)
      values. RESULTS: Compared with ANIM, ADIM decreases symptomatic hypoglycemia by
      approximately 2 fold (p < 0.001) and severe hypoglycemia by 7-10 fold (p = 0.04).
      ADIM somewhat reduced BG variation. Mean HbA1c was comparable on ADIM (7.9 +/-
      0.8 %; 63 +/- 9 mmol/mol) and ANIM (8.2 +/- 0.7 %; 66 +/- 8 mmol/mol).
      CONCLUSIONS: Using a free-mixing preparation of aspart and detemir insulin
      decreases hypoglycemia in young children with type 1 diabetes.

PMID- 24888576
TI  - Pancreaticogastrostomy is associated with significantly less pancreatic fistula
      than pancreaticojejunostomy reconstruction after pancreaticoduodenectomy: a meta
      analysis of seven randomized controlled trials.
AB  - OBJECTIVES: This study aimed to compare pancreaticojejunostomy (PJ) with
      pancreaticogastrostomy (PG) after pancreaticoduodenectomy (PD). METHODS: A
      literature search of PubMed and the Cochrane Central Register of Controlled
      Trials for studies comparing PJ with PG after PD was conducted. The primary
      outcome for meta-analysis was pancreatic fistula. Secondary outcomes were
      morbidity, mortality, biliary fistula, intra-abdominal fluid collection, hospital
      length of stay (LoS), postoperative haemorrhage and reoperation. Outcome measures
      were odds ratios (ORs) and mean differences with 95% confidence intervals (CIs).
      RESULTS: Seven recent RCTs encompassing 1121 patients (559 PJ and 562 PG cases)
      were involved in this meta-analysis. Incidences of pancreatic fistula (10.6%
      versus 18.5%; OR 0.52, 95% CI 0.37-0.74; P = 0.0002), biliary fistula (2.3%
      versus 5.7%; OR 0.42, 95% CI 0.03-3.15; P = 0.03) and intra-abdominal fluid
      collection (8.0% versus 14.7%; OR 0.50, 95% CI 0.34-0.74; P = 0.0005) were
      significantly lower in the PG than the PJ group, as was hospital LoS (weighted
      mean difference: -1.85, 95% CI -3.23 to -0.47; P = 0.008). Subgroup analysis
      indicated that severe pancreatic fistula (grades B or C) occurred less frequently
      in the PG than the PJ group (8.3% versus 20.5%; OR 0.37, 95% CI 0.23-0.59; P <
      0.00001). However, there was no significant difference in morbidity (48.9% versus
      51.0%; OR 0.90, 95% CI 0.70-1.16; P = 0.41), mortality (3.2% versus 3.5%; OR
      0.82, 95% CI 0.43-1.58; P = 0.56), delayed gastric emptying (16.6% versus 14.7%;
      relative risk: 1.02, 95% CI 0.62-1.68; P = 0.94), postoperative haemorrhage (9.6%
      versus 11.1%; OR 0.82, 95% CI 0.54-1.24; P = 0.35) or reoperation (9.9% versus
      9.8%; OR 0.93, 95% CI 0.60-1.43; P = 0.73). CONCLUSIONS: Pancreaticogastrostomy
      provides benefits over PJ after PD, including in the incidences of pancreatic
      fistula, biliary fistula and intra-abdominal fluid collection and in hospital
      LoS. Therefore, PG is recommended as a safer and more reasonable alternative to
      PJ reconstruction after PD.

PMID- 24888579
TI  - Does Coxiella burnetii affect reproduction in cattle? A clinical update.
AB  - Q fever is a zoonosis produced by Coxiella burnetii, a bacterium that is widely
      distributed worldwide. Domestic ruminants are the most important source of C.
      burnetii for human infection. In sheep and goats, abortion is the main clinical
      consequence of infection, yet the symptoms described in cattle have so far been
      inconsistent. Q fever has been also scarcely reported in cattle, most likely
      because of its difficult diagnosis at the farm level and because of the many
      existing responsible C. burnetii strains. In this report, the effects of C.
      burnetii infection or Q fever disease on the reproductive behaviour of dairy
      cattle are reviewed, with special emphasis placed on the scarcity of data
      available and possible control actions discussed. 

PMID- 24888580
TI  - Consequences of hypertension and chronic obstructive pulmonary disease,
      healthcare-seeking behaviors of patients, and responses of the health system: a
      population-based cross-sectional study in Bangladesh.
AB  - BACKGROUND: Non-communicable diseases are a threat to human health and economic
      development of low-income countries. Hypertension (HT) and chronic obstructive
      pulmonary disease (COPD) are two major causes of deaths, worldwide. This study
      assesses the health status, health-care seeking, and health provider responses
      among patients with these conditions. METHODS: The study carried out population
      based cross-sectional survey in a rural and an urban surveillance area in
      Bangladesh. It interviewed all patients identified with HT and COPD at home using
      a structured questionnaire on the health consequences, healthcare-seeking
      behaviours, and coping strategies. Qualitative techniques identified key factors
      relating to the behaviours of patients and providers. RESULTS: COPD and HT
      correlate with lower activities of daily living (ADL) scores. The odds ratio (OR)
      for ADL scores in the combied conditions are high (OR: 3.04, p < 0.05) as
      compared to hypertension. Financial crises occur significantly more frequently
      among COPD patients in the urban site as compared to those in rural ares (12.5%
      vs. 2.4%, p < 0.01). Self-treatment at the onset is common. Seeking care from
      trained providers is higher in urban settings and is higher for HT. Referral for
      both COPD and hypertension was inadequate until the disease severity increased.
      CONCLUSIONS: COPD and HT significantly are associated with lower ADL scores and
      financial problems. Public-sector primary healthcare facilities should be better
      organised to address both conditions with the aim to reduce household poverty.

PMID- 24888582
TI  - Energy position of the transport path in disordered organic semiconductors.
AB  - The concept of transport energy is the most transparent theoretical approach to
      describe hopping transport in disordered systems with steeply energy dependent
      density of states (DOS), in particular in organic semiconductors with Gaussian
      DOS. This concept allows one to treat hopping transport in the framework of a
      simple multiple-trapping model, replacing the mobility edge by a particular
      energy level called the transport energy. However, there is no consensus among
      researchers on the position of this transport level. In this article, we suggest
      a numerical procedure to find out the energy level most significantly
      contributing to charge transport in organic semiconductors. The procedure is
      based on studying the effects of DOS modifications on the charge carrier mobility
      in straightforward computer simulations. We also show why the most frequently
      visited energy, computed in several numerical studies to determine the transport
      energy, is not representative for charge transport.

PMID- 24888581
TI  - Probing water density and dynamics in the chaperonin GroEL cavity.
AB  - ATP-dependent binding of the chaperonin GroEL to its cofactor GroES forms a
      cavity in which encapsulated substrate proteins can fold in isolation from bulk
      solution. It has been suggested that folding in the cavity may differ from that
      in bulk solution owing to steric confinement, interactions with the cavity walls,
      and differences between the properties of cavity-confined and bulk water.
      However, experimental data regarding the cavity-confined water are lacking. Here,
      we report measurements of water density and diffusion dynamics in the vicinity of
      a spin label attached to a cysteine in the Tyr71 -> Cys GroES mutant obtained
      using two magnetic resonance techniques: electron-spin echo envelope modulation
      and Overhauser dynamic nuclear polarization. Residue 71 in GroES is fully exposed
      to bulk water in free GroES and to confined water within the cavity of the GroEL
      GroES complex. Our data show that water density and translational dynamics in the
      vicinity of the label do not change upon complex formation, thus indicating that
      bulk water-exposed and cavity-confined GroES surface water share similar
      properties. Interestingly, the diffusion dynamics of water near the GroES surface
      are found to be unusually fast relative to other protein surfaces studied. The
      implications of these findings for chaperonin-assisted folding mechanisms are
      discussed. 

PMID- 24888583
TI  - Urotensin II inhibits arginine vasotocin and stimulates isotocin release from
      nerve endings in the pituitary of gilthead sea bream (Sparus aurata).
AB  - The aim of this in vitro study was to determine whether arginine vasotocin (AVT)
      and isotocin (IT) release from nerve endings is affected by urotensin II (UII) in
      gilthead sea bream pituitary. Primary cultures of pituitary cells were exposed to
      10(-12), 10(-10), and 10(-8) M UII for 6, 24, and 48 hr. AVT and IT contents were
      determined in the culture media by high performance liquid chromatography (HPLC).
      UII at all doses decreased AVT release after 6, 24, and 48 hr of incubation. IT
      release was increased by UII only after 24 hr of incubation. This study, for the
      first time, indicates that UII affects AVT and IT release from nerve endings in
      the pituitary of Sparus aurata. It is presumed that UII together with AVT and IT
      may control response to different salinities in fishes.

PMID- 24888584
TI  - 'Doubling down' on the autophagy pathway to suppress tumor growth.
AB  - In this issue of Genes & Development, Wei and colleagues (pp. 1204-1216) use
      elegant genetic approaches to simultaneously delete the essential autophagy gene
      FIP200 (FAK family-interacting protein of 200 kDa) and the signaling adaptor
      p62/SQSTM1 within established murine tumors, which reveals an unexpected
      synergism between the autophagy pathway and p62 in driving tumor growth.
      Intriguingly, these observations suggest that the combined targeting of autophagy
      and p62 may serve as an effective approach to treat specific cancers. 

PMID- 24888585
TI  - How to build segregation complexes in bacteria: Use bridges.
AB  - In this issue of Genes & Development, Graham and colleagues (pp. 1228-1238)
      examine how ParBs, which bind to prokaryotic centromere-like partition sites,
      spread into nearby nonspecific DNA and assemble into higher-order protein-DNA
      complexes. Spreading is accomplished by looping rather than one-dimensional
      filamentation, thereby compacting the DNA into an extensively bridged complex. 

PMID- 24888587
TI  - Pronounced cohabitation of active immunoglobulin genes from three different
      chromosomes in transcription factories during maximal antibody synthesis.
AB  - To understand the relationships between nuclear organization and gene expression
      in a model system, we employed three-dimensional imaging and chromatin
      immunoprecipitation (ChIP)-chromosome conformation capture (3C) techniques to
      investigate the topographies of the immunoglobulin (Ig) genes and transcripts
      during B-cell development. Remarkably, in plasma cells, when antibody synthesis
      peaks, active Ig genes residing on three different chromosomes exhibit pronounced
      colocalizations in transcription factories, often near the nuclear periphery, and
      display trans-chromosomal enhancer interactions, and their transcripts frequently
      share interchromatin trafficking channels. Conceptually, these features of
      nuclear organization maximize coordinated transcriptional and transcript
      trafficking control for potentiating the optimal cytoplasmic assembly of the
      resulting translation products into protein multimers.

PMID- 24888586
TI  - Mammary stem cells and the differentiation hierarchy: current status and
      perspectives.
AB  - The mammary epithelium is highly responsive to local and systemic signals, which
      orchestrate morphogenesis of the ductal tree during puberty and pregnancy. Based
      on transplantation and lineage tracing studies, a hierarchy of stem and
      progenitor cells has been shown to exist among the mammary epithelium. Lineage
      tracing has highlighted the existence of bipotent mammary stem cells (MaSCs) in
      situ as well as long-lived unipotent cells that drive morphogenesis and
      homeostasis of the ductal tree. Moreover, there is accumulating evidence for a
      heterogeneous MaSC compartment comprising fetal MaSCs, slow-cycling cells, and
      both long-term and short-term repopulating cells. In parallel, diverse luminal
      progenitor subtypes have been identified in mouse and human mammary tissue.
      Elucidation of the normal cellular hierarchy is an important step toward
      understanding the "cells of origin" and molecular perturbations that drive breast
      cancer.

PMID- 24888588
TI  - MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain
      biosynthesis upon ER stress.
AB  - MZB1 (pERp1) is a B-cell-specific and endoplasmic reticulum (ER)-localized
      protein implicated in antibody secretion and integrin-mediated cell adhesion.
      Here, we examine the role of MZB1 in vivo by conditional gene inactivation in the
      mouse germline and at different stages of B lymphopoiesis. Deletion of MZB1
      impairs humoral immune responses and antibody secretion in plasma cells that
      naturally undergo ER stress. In addition, we found that experimental induction of
      ER stress by tunicamycin injections in mice results in a block of pro-B-cell to
      pre-B-cell differentiation specifically in Mzb1(-/-) mice. A similar
      developmental block was observed in Mzb1(fl/fl)mb1(Cre) mice, whereby a Cre
      recombinase-induced genotoxic stress unmasks a role for MZB1 in the surface
      expression of immunoglobulin u heavy chains (uHCs). MZB1 associates directly with
      the substrate-specific chaperone GRP94 (also called HSP90B1 or gp96) in an ATP
      sensitive manner and is required for the interaction of GRP94 with uHCs upon ER
      stress. Thus, MZB1 seems to act as a substrate-specific cochaperone of GRP94 that
      enables proper biosynthesis of uHCs under conditions of ER stress.

PMID- 24888589
TI  - MuLV-related endogenous retroviral elements and Flt3 participate in aberrant end
      joining events that promote B-cell leukemogenesis.
AB  - During V(D)J recombination of immunoglobulin genes, p53 and nonhomologous end
      joining (NHEJ) suppress aberrant rejoining of DNA double-strand breaks induced by
      recombinase-activating genes (Rags)-1/2, thus maintaining genomic stability and
      limiting malignant transformation during B-cell development. However, Rag
      deficiency does not prevent B-cell leukemogenesis in p53/NHEJ mutant mice,
      revealing that p53 and NHEJ also suppress Rag-independent mechanisms of B-cell
      leukemogenesis. Using several cytogenomic approaches, we identified a novel class
      of activating mutations in Fms-like tyrosine kinase 3 (Flt3), a receptor tyrosine
      kinase important for normal hematopoiesis in Rag/p53/NHEJ triple-mutant (TM) B
      cell leukemias. These mutant Flt3 alleles were created by complex genomic
      rearrangements with Moloney leukemia virus (MuLV)-related endogenous retroviral
      (ERV) elements, generating ERV-Flt3 fusion genes encoding an N-terminally
      truncated mutant form of Flt3 (trFlt3) that was transcribed from ERV long
      terminal repeats. trFlt3 protein lacked most of the Flt3 extracellular domain and
      induced ligand-independent STAT5 phosphorylation and proliferation of
      hematopoietic progenitor cells. Furthermore, expression of trFlt3 in p53/NHEJ
      mutant hematopoietic progenitor cells promoted development of clinically
      aggressive B-cell leukemia. Thus, repetitive MuLV-related ERV sequences can
      participate in aberrant end-joining events that promote development of aggressive
      B-cell leukemia.

PMID- 24888593
TI  - Acute gynaecological services in Australia--time for a change.

PMID- 24888590
TI  - p62/SQSTM1 synergizes with autophagy for tumor growth in vivo.
AB  - Autophagy is crucial for cellular homeostasis and plays important roles in
      tumorigenesis. FIP200 (FAK family-interacting protein of 200 kDa) is an essential
      autophagy gene required for autophagy induction, functioning in the ULK1-ATG13
      FIP200 complex. Our previous studies showed that conditional knockout of FIP200
      significantly suppressed mammary tumorigenesis, which was accompanied by
      accumulation of p62 in tumor cells. However, it is not clear whether FIP200 is
      also required for maintaining tumor growth and how the increased p62 level
      affects the growth in autophagy-deficient FIP200-null tumors in vivo. Here, we
      describe a new system to delete FIP200 in transformed mouse embryonic fibroblasts
      as well as mammary tumor cells following their transplantation and show that
      ablation of FIP200 significantly reduced growth of established tumors in vivo.
      Using similar strategies, we further showed that either p62 knockdown or p62
      deficiency in established FIP200-null tumors dramatically impaired tumor growth.
      The stimulation of tumor growth by p62 accumulation in FIP200-null tumors is
      associated with the up-regulated activation of the NF-kappaB pathway by p62.
      Last, we showed that overexpression of the autophagy master regulator TFEB(S142A)
      increased the growth of established tumors, which correlated with the increased
      autophagy of the tumor cells. Together, our studies demonstrate that p62 and
      autophagy synergize to promote tumor growth, suggesting that inhibition of both
      pathways could be more effective than targeting either alone for cancer therapy.

PMID- 24888591
TI  - RNA remodeling by bacterial global regulator CsrA promotes Rho-dependent
      transcription termination.
AB  - RNA-binding protein CsrA is a key regulator of a variety of cellular processes in
      bacteria, including carbon and stationary phase metabolism, biofilm formation,
      quorum sensing, and virulence gene expression in pathogens. CsrA binds to
      bipartite sequence elements at or near the ribosome loading site in messenger RNA
      (mRNA), most often inhibiting translation initiation. Here we describe an
      alternative novel mechanism through which CsrA achieves negative regulation. We
      show that CsrA binding to the upstream portion of the 5' untranslated region of
      Escherichia coli pgaA mRNA-encoding a polysaccharide adhesin export protein
      unfolds a secondary structure that sequesters an entry site for transcription
      termination factor Rho, resulting in the premature stop of transcription. These
      findings establish a new paradigm for bacterial gene regulation in which
      remodeling of the nascent transcript by a regulatory protein promotes Rho
      dependent transcription attenuation.

PMID- 24888592
TI  - Phenolic compounds involved in grafting incompatibility of Vitis spp: development
      and validation of an analytical method for their quantification.
AB  - INTRODUCTION: Graft incompatibility of Vitis spp is an unresolved worldwide
      problem with important economic consequences. Grafting comprises a complex set of
      morphological and physiological alterations, in which the phenolic compounds seem
      to be strongly involved. Therefore, a detailed analysis and recognition of
      structural phenolic compounds diversity in the two partners of a Vitis graft is
      of great importance to evaluate their role as markers of graft establishment.
      OBJECTIVE: To optimise a sample extraction method, and to develop and validate a
      high-performance liquid chromatography (HPLC) method for the simultaneous
      determination of phenolic acids and flavonols in the graft union so as to
      understand their behaviour in the metabolism of the scion-rootstock system, using
      compatible and incompatible combinations of a Syrah cultivar and two rootstocks
      (R110 and SO4). METHODS: Sixty extracts of Vitis grafting tissues were prepared
      and analysed by HPLC for the qualitative and quantitative determination of their
      phenolic profile. RESULTS: Among the phenolic compounds identified in the
      samples, one benzoic acid (gallic acid), three cinnamic acids (caffeic acid,
      ferulic acid and sinapic acid) and two flavonols (catechin and epicatechin) are
      potentially suitable as markers of graft incompatibility. CONCLUSION: The method
      developed presents good performance and lends itself readily for application in
      routine analysis of the phenolic composition of Vitis grafting tissues to
      distinguish compatible and incompatible combinations in the graft callusing
      stage.

PMID- 24888594
TI  - Evidence for ethnic and environmental contributions to frequency of ovarian clear
      cell carcinoma.
AB  - BACKGROUND: Ovarian clear cell carcinoma (OCCC) is reportedly more common in
      Asians than Caucasians. We investigated the epidemiology of OCCC in an Asian
      population. MATERIALS AND METHODS: Cases of epithelial ovarian cancer (EOC)
      diagnosed between January 2004 and December 2009 in a gynaecologic oncology unit
      were studied retrospectively. Patient details and tumour characteristics were
      retrieved from hospital records and tested for their association with OCCC by
      univariate and binomial logistic regression analysis. A time trend in the
      proportion of OCCC among EOC was computed with data from the National Cancer
      Registry of Singapore (1968-2006). RESULTS: The institutional cohort of 341 cases
      included 81 OCCC and 260 non-OCCC EOC. Independent risk factors for OCCC were
      nulliparity (OR = 1.36) and endometriosis (OR = 4.87). Compared with other EOC,
      OCCC was significantly larger in tumour size (13.5 vs. 11.3 cm), more frequently
      located unilaterally (84.3 vs. 65.5%), diagnosed at FIGO stage-1 (63.0 vs. 33.9%)
      and negative for serum CA125 (34.2 vs. 8.2%), and less often (53 vs. 85%)
      associated with a positive Risk of Malignancy Index. Nation-wide statistics
      revealed a steady increase in the proportion of OCCC among EOC from 5.2 to 13.4%
      between 1968 and 2006. The frequency of OCCC in Singapore was higher than
      American Whites, similar to American Asians but lower than Japanese. CONCLUSION:
      The difference in epidemiologic and tumour characteristics between OCCC and other
      EOC was nondiscriminatory. Three distinct ethnic-related clusters of frequency
      distribution globally and the rising trend in proportion of OCCC in Singapore
      suggested that ethnic-genetic predisposition and economy-related environmental
      factors contributed to development of OCCC.

PMID- 24888595
TI  - Placenta percreta: multidisciplinary team may not be enough.

PMID- 24888596
TI  - Re: ANZJOG-2013-0458--Placenta percreta: multidisciplinary team may not be
      enough.

PMID- 24888597
TI  - Re: Future therapies for pre-eclampsia: beyond treading water.

PMID- 24888598
TI  - Re: Future therapies for pre-eclampsia: beyond treading water.

PMID- 24888599
TI  - SCIg vs. IVIg: let's give patients the choice!

PMID- 24888600
TI  - Autologous human cytomegalovirus-specific cytotoxic T cells as rescue therapy for
      ulcerative enteritis in primary immunodeficiency.
AB  - PURPOSE: Patients affected by primary immunodeficiency usually undergo a wide
      range of infections, including reactivation of latent ones. Here we report two
      cases suffering from late-onset combined immunodeficiency in which ulcerative
      enteritis due to human Cytomegalovirus caused a life-threatening malabsorption
      syndrome. METHODS: The assessment of the viral load was carried out on both blood
      and mucosal samples by quantitative real-time polymerase chain reaction assay.
      The generation of autologous virus-specific cytotoxic T cell lines was performed
      according to Good Manufacturing Practice protocol after peripheral blood
      mononuclear cells were collected through a single leukapheresis. RESULTS: In both
      patients, the viral load resulted negligible in peripheral blood, but very high
      in mucosal specimens (range 1.064 - 1.031.692 copies/10(5) cells). After two
      rounds of antiviral therapy proved unsuccessful, the generation of virus-specific
      cytotoxic T cell lines was carried out despite severe lymphopenia, and their
      infusion resulted safe and durably effective in healing intestinal ulcerations
      and resetting the viral load. CONCLUSIONS: Virus-specific cellular therapy was
      useful in reconstituting specific immunity and treating severe human
      Cytomegalovirus-related enteritis in patients with primary immunodeficiency.

PMID- 24888602
TI  - Novel NFKB2 mutation in early-onset CVID.
AB  - Common variable immunodeficiency (CVID) is heterogeneous, clinically,
      immunologically and genetically. The majority of genetic mechanisms leading to
      CVID remain elusive. We studied a Greek Cypriot family of non-consanguineous
      parents. Two children were diagnosed with CVID at an early age. Whole exome
      sequencing revealed 8bp deletion in the C-terminal part of NFKB2 gene associated
      with disease. The mutation leads to a frameshift (p.Asp865Valfs*17) altering 17 C
      terminal amino acids from residue 865, and creating a premature stop-codon
      resulting in a truncated protein, 19 amino acids shorter than wild type
      (p100Delta19). We validated the results with Dye-termination sequencing and
      Western blot, and confirmed that the conserved residue at 866 is mutated from
      serine to arginine in p100Delta19, leaving the mutant protein unphosphorylated at
      this critical regulatory position. Consequently, NFKB2/p100 processing and
      nuclear translocation were abrogated. Using flow cytometry, we further
      demonstrated that there was a reduction in B cells (CD19+), switched memory B
      cells (CD27+IgD-) and T follicular helper (Tfh) cells (both CD4+CXCR5+ and
      CD4+CXCR5Hi) in a CVID patient with NFKB2/p100Delta19, compared to healthy
      controls. These data support the notion that the non-canonical NFkappaB pathway
      plays an important role in B cell differentiation and the development of Tfh
      cells, and may pave the way for better understanding of the pathology of CVID. 

PMID- 24888604
TI  - Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows.
AB  - BACKGROUND: Hepatic lipidosis or fatty liver disease is a major metabolic
      disorder of high-producing dairy cows that compromises animal performance and,
      hence, causes heavy economic losses worldwide. This syndrome, occurring during
      the critical transition from gestation to early lactation, leads to an impaired
      health status, decreased milk yield, reduced fertility and shortened lifetime.
      Because the prevailing clinical chemistry parameters indicate advanced liver
      damage independently of the underlying disease, currently, hepatic lipidosis can
      only be ascertained by liver biopsy. We hypothesized that the condition of fatty
      liver disease may be accompanied by an altered profile of endogenous metabolites
      in the blood of affected animals. RESULTS: To identify potential small-molecule
      biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy
      cows were subjected to a targeted metabolomics screen by triple quadrupole mass
      spectrometry. A subsequent multivariate test involving principal component and
      linear discriminant analyses yielded 29 metabolites (amino acids,
      phosphatidylcholines and sphingomyelines) that, in conjunction, were able to
      distinguish between dairy cows with no hepatic lipidosis and those displaying
      different stages of the disorder. CONCLUSIONS: This proof-of-concept study
      indicates that metabolomic profiles, including both amino acids and lipids,
      distinguish hepatic lipidosis from other peripartal disorders and, hence, provide
      a promising new tool for the diagnosis of hepatic lipidosis. By generating
      insights into the molecular pathogenesis of hepatic lipidosis, metabolomics
      studies may also facilitate the prevention of this syndrome.

PMID- 24888603
TI  - Physiological sodium concentrations enhance the iodide affinity of the Na+/I-
      symporter.
AB  - The Na(+)/I(-) symporter (NIS) mediates active I(-) transport--the first step in
      thyroid hormonogenesis--with a 2Na(+):1I(-) stoichiometry. NIS-mediated (131)I(-)
      treatment of thyroid cancer post-thyroidectomy is the most effective targeted
      internal radiation cancer treatment available. Here to uncover mechanistic
      information on NIS, we use statistical thermodynamics to obtain Kds and estimate
      the relative populations of the different NIS species during Na(+)/anion binding
      and transport. We show that, although the affinity of NIS for I(-) is low (Kd=224
      MUM), it increases when Na(+) is bound (Kd=22.4 MUM). However, this Kd is still
      much higher than the submicromolar physiological I(-) concentration. To overcome
      this, NIS takes advantage of the extracellular Na(+) concentration and the
      pronounced increase in its own affinity for I(-) and for the second Na(+)
      elicited by binding of the first. Thus, at physiological Na(+) concentrations,
      ~79% of NIS molecules are occupied by two Na(+) ions and ready to bind and
      transport I(-).

PMID- 24888605
TI  - A chemiluminescent light system in combination with toluidine blue to assess
      suspicious oral lesions-clinical evaluation and review of the literature.
AB  - OBJECTIVES: The aim of the study was an evaluation of an acetic acid wash and
      chemiluminescent light system in combination with toluidine blue in order to
      detect visual identified, potentially malignant lesions. MATERIALS AND METHODS:
      Forty-four patients with 50 oral lesions of primary uncertain visible dignity
      were included. Next to a clinical examination, a screening with ViziLite(r) (VL)
      as well as toluidine blue (TB; together ViziLite(r) Plus (VLP)) was conducted.
      Histopathology served as gold standard and sensitivity (SE), specificity (SP),
      positive as well as negative predictive value (PPV, NPV) was calculated
      descriptively. Additionally, a PubMed literature search using the key words
      "ViziLite" and "chemiluminescence oral cancer" was conducted. RESULTS:
      Histological diagnosis showed 40 lesions of reactive/inflammatory nature,
      moderate dysplasia (n = 3) and oral squamous cell carcinoma (OSCC n = 7). All
      OSCCs and one dysplasia were identified correct via clinical diagnosis (SE 90 %,
      SP 100 %, PPV 100 %, NPV 97.5 %). VL examination could show all malignancies with
      low specificity (SE 100 %, SP 30 %, PPV 26 %, NPV 100 %). TB and VLP were
      positive in all cases of cancer and in one case of inflammation (SE 80 %, SP 97.5
      %, PPV 89 %, NPV 95 %). In the review, eight clinical trials with similar results
      were included. CONCLUSIONS: The adjunct of TB to VL reduces the number of false
      positives without increasing the rate of false negatives. CLINICAL RELEVANCE:
      Clinical evidence to justify the additional cost of the system for diagnosis of
      suspicious lesions is weak. However, for the potential role of VLP in detection
      of lesions not otherwise identified in the visual exam in general dental practice
      further studies are required.

PMID- 24888606
TI  - Expression-based network biology identifies immune-related functional modules
      involved in plant defense.
AB  - BACKGROUND: Plants respond to diverse environmental cues including microbial
      perturbations by coordinated regulation of thousands of genes. These intricate
      transcriptional regulatory interactions depend on the recognition of specific
      promoter sequences by regulatory transcription factors. The combinatorial and
      cooperative action of multiple transcription factors defines a regulatory network
      that enables plant cells to respond to distinct biological signals. The
      identification of immune-related modules in large-scale transcriptional
      regulatory networks can reveal the mechanisms by which exposure to a pathogen
      elicits a precise phenotypic immune response. RESULTS: We have generated a large
      scale immune co-expression network using a comprehensive set of Arabidopsis
      thaliana (hereafter Arabidopsis) transcriptomic data, which consists of a wide
      spectrum of immune responses to pathogens or pathogen-mimicking stimuli
      treatments. We employed both linear and non-linear models to generate Arabidopsis
      immune co-expression regulatory (AICR) network. We computed network topological
      properties and ascertained that this newly constructed immune network is densely
      connected, possesses hubs, exhibits high modularity, and displays hallmarks of a
      "real" biological network. We partitioned the network and identified 156 novel
      modules related to immune functions. Gene Ontology (GO) enrichment analyses
      provided insight into the key biological processes involved in determining finely
      tuned immune responses. We also developed novel software called OCCEAN (One Click
      Cis-regulatory Elements ANalysis) to discover statistically enriched promoter
      elements in the upstream regulatory regions of Arabidopsis at a whole genome
      level. We demonstrated that OCCEAN exhibits higher precision than the existing
      promoter element discovery tools. In light of known and newly discovered cis
      regulatory elements, we evaluated biological significance of two key immune
      related functional modules and proposed mechanism(s) to explain how large sets of
      diverse GO genes coherently function to mount effective immune responses.
      CONCLUSIONS: We used a network-based, top-down approach to discover immune
      related modules from transcriptomic data in Arabidopsis. Detailed analyses of
      these functional modules reveal new insight into the topological properties of
      immune co-expression networks and a comprehensive understanding of multifaceted
      plant defense responses. We present evidence that our newly developed software,
      OCCEAN, could become a popular tool for the Arabidopsis research community as
      well as potentially expand to analyze other eukaryotic genomes.

PMID- 24888607
TI  - Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean
      patients with non-small-cell lung cancer highlights significantly higher ALK
      rearrangement rate in advanced stage.
AB  - BACKGROUND: Simultaneous genotyping has advantages in turnaround time and
      detecting the real mutational prevalence in unresectable non-small-cell lung
      cancer (NSCLC), a group not previously genetically characterized. METHODS: We
      developed simultaneous panel of screening EGFR and KRAS mutations by direct
      sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ
      hybridization (FISH) in multicenter manner. RESULTS: Of 510 NSCLC Korean
      patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS
      (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations.
      Although several well-known associations between genotypes and clinical
      characteristics were identified, we found no relationship between ALK
      rearrangement and sex or smoking history. Unlike the other genotype mutations,
      ALK rearrangement was associated with advanced disease. Among the ALK-negative
      group, patients with 10-15% of ALK FISH split shared characteristics, such as
      younger age and advanced stage disease, more with the ALK-positive group (>15%
      ALK FISH split) than <10% ALK FISH split group. CONCLUSIONS: Simultaneous panel
      genotyping revealed more prevalent ALK rearrangements than reported in previous
      studies and their strong association with advanced stage irrespective of sex or
      smoking history. ALK rearrangement seems to be a marker for aggressive tumor
      biology and should be assessed in advanced disease.

PMID- 24888608
TI  - Assessing the hydrocarbon degrading potential of indigenous bacteria isolated
      from crude oil tank bottom sludge and hydrocarbon-contaminated soil of Azzawiya
      oil refinery, Libya.
AB  - The disposal of hazardous crude oil tank bottom sludge (COTBS) represents a
      significant waste management burden for South Mediterranean countries. Currently,
      the application of biological systems (bioremediation) for the treatment of COTBS
      is not widely practiced in these countries. Therefore, this study aims to develop
      the potential for bioremediation in this region through assessment of the
      abilities of indigenous hydrocarbonoclastic microorganisms from Libyan Hamada
      COTBS for the biotreatment of Libyan COTBS-contaminated environments. Bacteria
      were isolated from COTBS, COTBS-contaminated soil, treated COTBS-contaminated
      soil, and uncontaminated soil using Bushnell Hass medium amended with Hamada
      crude oil (1 %) as the main carbon source. Overall, 49 bacterial phenotypes were
      detected, and their individual abilities to degrade Hamada crude and selected
      COBTS fractions (naphthalene, phenanthrene, eicosane, octadecane and hexane) were
      evaluated using MT2 Biolog plates. Analyses using average well colour development
      showed that ~90 % of bacterial isolates were capable of utilizing representative
      aromatic fractions compared to 51 % utilization of representative aliphatics.
      Interestingly, more hydrocarbonoclastic isolates were obtained from treated
      contaminated soils (42.9 %) than from COTBS (26.5 %) or COTBS-contaminated (30.6
      %) and control (0 %) soils. Hierarchical cluster analysis (HCA) separated the
      isolates into two clusters with microorganisms in cluster 2 being 1.7- to 5-fold
      better at hydrocarbon degradation than those in cluster 1. Cluster 2 isolates
      belonged to the putative hydrocarbon-degrading genera; Pseudomonas, Bacillus,
      Arthrobacter and Brevundimonas with 57 % of these isolates being obtained from
      treated COTBS-contaminated soil. Overall, this study demonstrates that the
      potential for PAH degradation exists for the bioremediation of Hamada COTBS
      contaminated environments in Libya. This represents the first report on the
      isolation of hydrocarbonoclastic bacteria from Libyan COTBS and COTBS
      contaminated soil.

PMID- 24888609
TI  - Long-term monitoring and modeling of polychlorinated dibenzo-p-dioxins and
      dibenzofurans from municipal solid waste incinerators and surrounding area in
      northern Taiwan.
AB  - Municipal solid waste incinerators (MSWIs) have long been the major contributors
      of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) to ambient air
      in Taiwan. After stringent MSWI emission standards were introduced in 2001, the
      long-term continuous monitoring of flue gas and ambient air quality became
      necessary to ensure the effectiveness of the related control strategies. Three
      MSWIs and the surrounding ambient air were investigated in the current study for
      PCDD/F characteristics during 2006 to 2011. The average concentrations in the
      flue gas ranged from 0.008 ~ 0.0488 ng I-TEQ/Nm(3), which is much less than the
      emission standard in Taiwan (0.1 ng I-TEQ/Nm(3)) (I-TEQ is the abbreviation of
      International Toxic Equivalent). This led to extremely low levels in the ambient
      air, 0.0255 pg I-TEQ/Nm(3), much less than the levels seen in most urban areas
      around the world. Additionally, the results obtained using the Industrial Source
      Complex Short-Term Dispersion Model (ISCST3) indicate that the PCDD/F
      contributions from the three MSWIs to the ambient air were only in the range from
      0.164 ~ 0.723 %. Principal component analysis (PCA) showed that the PCDD/Fs in
      the air samples had very similar characteristics to those from mobile sources.
      The results thus show that stringent regulations have been an effective control
      strategy, especially for urban areas, such as Taipei City.

PMID- 24888610
TI  - Solar energy for wastewater treatment: review of international technologies and
      their applicability in Brazil.
AB  - Several studies have reported the adverse effects of recalcitrant compounds and
      emerging contaminants present in industrial effluents, which are not degradable
      by ordinary biological treatment. Many of these compounds are likely to
      accumulate in living organisms through the lipid layer. At concentrations above
      the limits of biological tolerance, these compounds can be harmful to the
      ecosystem and may even reach humans through food chain biomagnification. In this
      regard, advanced oxidation processes (AOPs) represent an effective alternative
      for the removal of the pollutants. This study focused on the AOP involving the
      use of ultraviolet radiation in homogeneous and heterogeneous systems. Based on
      the literature review, comparisons between natural and artificial light were
      established, approaching photoreactors constructive and operational
      characteristics. We concluded that the high availability of solar power in Brazil
      would make the implementation of the AOP using natural solar radiation for the
      decontamination of effluents feasible, thereby contributing to clean production
      and biodiversity conservation. This will serve as an important tool for the
      enforcement of environmental responsibility among public and private
      institutions. 

PMID- 24888611
TI  - Oxidative stress response in dye degrading bacterium Lysinibacillus sp. RGS
      exposed to Reactive Orange 16, degradation of RO16 and evaluation of toxicity.
AB  - Lysinibacillus sp. RGS degrades sulfonated azo dye Reactive Orange 16 (RO16)
      efficiently. Superoxide dismutase and catalase activity were tested to study the
      response of Lysinibacillus sp. RGS to the oxidative stress generated by RO16. The
      results demonstrated that oxidative stress enzymes not only protect the cell from
      oxidative stress but also has a probable role in decolorization along with an
      involvement of oxidoreductive enzymes. Formation of three different metabolites
      after degradation of RO16 has been confirmed by GC-MS analysis. FTIR analysis
      verified the degradation of functional groups of RO16, and HPTLC confirmed the
      removal of auxochrome group from the RO16 after degradation. Toxicity studies
      confirmed the genotoxic, cytotoxic, and phytotoxic nature of RO16 and the
      formation of less toxic products after the treatment of Lysinibacillus sp. RGS.
      Therefore, Lysinibacillus sp. RGS has a better perspective of bioremediation for
      textile wastewater treatment.

PMID- 24888612
TI  - Specificity of metal tolerance and use of excluder metallophytes for the
      phytostabilization of metal polluted soils: the case of Silene paradoxa L.
AB  - This work was planned for providing useful information about the use of excluder
      metallophytes for phytostabilization of soils contaminated also with elements
      scarcely represented in the metalliferous environment of origin. To this aim, we
      investigated tolerance and accumulation of several different elements in a
      metallicolous and a nonmetallicolous population of Silene paradoxa through a
      hydroponic experiment. S. paradoxa metallicolous population showed increased
      tolerance not only to all the metals highly represented in the environment of
      origin but also to some of those scarcely present. Therefore, our results deposed
      in favor of the occurrence of the co-tolerance phenomenon in S. paradoxa for some
      elements. Metal accumulation was higher in the roots than in the shoots and lower
      in the metallicolous population than in the nonmetallicolous one, thus showing
      tolerance mechanisms to be based largely on metal exclusion. Anyway, the relative
      contribution of avoidance and of internal tolerance to metal tolerance was shown
      to be element-dependent. Present data revealed that metallicolous plants can
      effectively posses metal co-tolerances, which deserve to be investigated; as
      such, plants can actually represent a precious and exploitable tool also for the
      phytostabilization of soils contaminated with elements underrepresented in the
      environment of their origin.

PMID- 24888613
TI  - Comparative study of non-invasive methods for assessing Daphnia magna embryo
      toxicity.
AB  - Embryos, unlike adults, are typically sessile, which allows for an increase in
      the available metrics that can be used to assess chemical toxicity. We
      investigate Daphnia magna development rate and oxygen consumption as toxicity
      metrics and compare them to arrested embryo development using four different
      techniques with potassium cyanide (KCN) as a common toxicant. The EC50 (95 % CI)
      for arrested development was 2,535 (1,747-3,677) MUg/L KCN. Using pixel intensity
      changes, recorded with difference imaging, we semi-quantitatively assessed a
      decrease in development rate at 200 MUg/L KCN, threefold lower than the arrested
      development lowest observed effect concentration (LOEC). Respirometry and self
      referencing (SR) microsensors were two unique techniques used to assess oxygen
      consumption. Using respirometry, an increase in oxygen consumption was found in
      the 5 MUg/L KCN treatment and a decrease for 148 MUg/L, but no change was found
      for the 78 MUg/L KCN treatment. Whereas, with SR microsensors, we were able to
      detect significant changes in oxygen consumption for all three treatments: 5, 78,
      and 148 MUg/L KCN. While SR offered the highest sensitivity, the respirometry
      platform developed for this study was much easier to use to measure the same
      endpoint. Oxygen consumption may be subject to change during the development
      process, meaning consumption assessment techniques may only be useful only for
      short-term experiments. Development rate was a more sensitive endpoint though was
      only reliable four of the six embryonic developmental stages examined. Despite
      being the least sensitive endpoint, arrested embryo development was the only
      technique capable of assessing the embryos throughout all developmental stages.
      In conclusion, each metric has advantages and limitations, but because all are
      non-invasive, it is possible to use any combination of the three.

PMID- 24888615
TI  - Selection of suitable lichen bioindicator species for monitoring climatic
      variability in the Himalaya.
AB  - Interspecific comparison in metals and PAHs profile in three lichen species,
      Flavoparmelia caperata, Phaeophyscia hispidula and Pyxine sorediata, were studied
      in different altitudinal gradients of the Western Himalayas. The species
      collected from 14 sites, enroute from Dehradun to Morinda (243 Km) including the
      trekking route 42 Km from Taluka to Morinda having an altitudinal gradient
      between 850-3,750 m, were analysed for their metals and PAHs. The species showed
      similar metal as well as PAHs profile under similar altitudinal gradients in the
      sequence of F. caperata > P. hispidula > P. sorediata. The difference in
      pollutant concentrations within each lichen species may be related to intrinsic
      attributes of the species, such as thallus morphology and the presence of lichen
      substances which are responsible for the sensitivity and accumulation potential
      of a particular species. Novelty of the present study lies on the fact that all
      the species show a similar efficiency of reflecting the environmental condition
      of the area, albeit the coefficient values of individual species for individual
      pollutant obtained by three-factor ANOVA revealed that the bioaccumulation
      affinity of F. caperata is significantly higher than P. hispidula and P.
      sorediata. For individual metals, F. caperata has a higher affinity for Al, Cr,
      Fe, Pb and Zn while P. hispidula has a significant positive affinity for Fe and
      Pb. PCA analysis of sites with respect to pollutant revealed the segregation of
      sites based on source and distance. Combining the bioaccumulation potential
      parameters along with geostatistical (GIS) techniques establishes that F.
      caperata species is a better accumulator of metals and PAHs in comparison to P.
      hispidula and P. sorediata in the temperate regions of the Himalaya.

PMID- 24888614
TI  - Biochemical and standard toxic effects of acetaminophen on the macrophyte species
      Lemna minor and Lemna gibba.
AB  - Acetaminophen is globally one of the most prescribed drugs due to its antipyretic
      and analgesic properties. However, it is highly toxic when the dosage surpasses
      the detoxification capability of an exposed organism, with involvement of an
      already described oxidative stress pathway. To address the issue of the
      ecotoxicity of acetaminophen, we performed acute exposures of two aquatic plant
      species, Lemna gibba and Lemna minor, to this compound. The selected biomarkers
      were number of fronds, biomass, chlorophyll content, lipid peroxidation (TBARS
      assay), and proline content. Our results showed marked differences between the
      two species. Acetaminophen caused a significant decrease in the number of fronds
      (EC50 = 446.6 mg/L), and the establishment of a dose-dependent peroxidative
      damage in L. minor, but not in L. gibba. No effects were reported in both species
      for the indicative parameters chlorophyll content and total biomass. However, the
      proline content in L. gibba was substantially reduced. The overall conclusions
      point to the occurrence of an oxidative stress scenario more prominent for L.
      minor. However, the mechanisms that allowed L. gibba to cope with acetaminophen
      exposure were distinct from those reported for L. minor, with the likely
      involvement of proline as antioxidant.

PMID- 24888616
TI  - Combined effects of silver nanoparticles and 17alpha-ethinylestradiol on the
      freshwater mudsnail Potamopyrgus antipodarum.
AB  - Ecotoxicological studies have shown that nanosilver is among the most toxic
      nanomaterials to aquatic organisms. However, research has so far focused on the
      determination of acute effects. Combined effects of nanosilver with other
      substances have not yet been studied in aquatic organisms. The present study
      aimed to investigate the chronic toxicity of nanosilver as well as the potential
      of nanosilver to influence the effects of co-occurring substances on the
      freshwater mudsnail Potamopyrgus antipodarum. In 28-day chronic toxicity
      experiments, the effects of nanosilver on the reproduction of P. antipodarum were
      assessed. In order to evaluate the influence of nanosilver on other substances,
      17alpha-ethinylestradiol (EE2) was chosen as model compound due to the well
      characterized effects on P. antipodarum. In addition to effects on reproduction,
      exposure to nanosilver and EE2 was monitored by determining the expression of
      estrogen-responsive transcripts (estrogen receptor and vitellogenin encoding
      genes). Exposure to nanosilver decreased the reproduction of P. antipodarum
      (EC10: 5.57 MUg l(-1); EC50: 15.0 MUg l(-1)). Exposure to EE2 significantly
      stimulated the embryo production at 25 ng l(-1). The presence of nanosilver led
      to increased EE2 effects at EE2 concentrations that had no influence on
      reproduction when applied in absence of nanosilver. In contrast, combined
      exposure to nanosilver decreased EE2 effects at concentrations that stimulated
      reproduction and the expression of estrogen responsive genes when applied in the
      absence of nanosilver. This is the first study demonstrating an influence of
      nanosilver on the effects of co-contaminants on aquatic organisms. The study
      further highlights the need for chronic experiments to properly assess
      environmental risks of nanosilver and their effects on co-occurring contaminants.

PMID- 24888617
TI  - Click chemistry approach to conventional vegetable tanning process: accelerated
      method with improved organoleptic properties.
AB  - Click chemistry approaches are tailored to generate molecular building blocks
      quickly and reliably by joining small units together selectively and covalently,
      stably and irreversibly. The vegetable tannins such as hydrolyzable and condensed
      tannins are capable to produce rather stable radicals or inhibit the progress of
      radicals and are prone to oxidations such as photo and auto-oxidation, and their
      anti-oxidant nature is well known. A lot remains to be done to understand the
      extent of the variation of leather stability, color variation (lightening and
      darkening reaction of leather), and poor resistance to water uptake for prolonged
      periods. In the present study, we have reported click chemistry approaches to
      accelerated vegetable tanning processes based on periodates catalyzed formation
      of oxidized hydrolysable and condensed tannins for high exhaustion with improved
      properties. The distribution of oxidized vegetable tannin, the thermal stability
      such as shrinkage temperature (T s) and denaturation temperature (T d),
      resistance to collagenolytic activities, and organoleptic properties of tanned
      leather as well as the evaluations of eco-friendly characteristics were
      investigated. Scanning electron microscopic analysis indicates the cross section
      of tightness of the leather. Differential scanning calorimetric analysis shows
      that the T d of leather is more than that of vegetable tanned or equal to
      aldehyde tanned one. The leathers exhibited fullness, softness, good color, and
      general appearance when compared to non-oxidized vegetable tannin. The developed
      process benefits from significant reduction in total solids and better
      biodegradability in the effluent, compared to non-oxidized vegetable tannins. 

PMID- 24888618
TI  - Bayesian importance parameter modeling of misaligned predictors: soil metal
      measures related to residential history and intellectual disability in children.
AB  - In this paper, we propose a novel spatial importance parameter hierarchical
      logistic regression modeling approach that includes measurement error from
      misalignment. We apply this model to study the relationship between the estimated
      concentration of soil metals at the residence of mothers and the development of
      intellectual disability (ID) in their children. The data consist of monthly
      computerized claims data about the prenatal experience of pregnant women living
      in nine areas within South Carolina and insured by Medicaid during January 1,
      1996 and December 31, 2001 and the outcome of ID in their children during early
      childhood. We excluded mother-child pairs if the mother moved to an unknown
      location during pregnancy. We identified an association of the ID outcome with
      arsenic (As) and mercury (Hg) concentration in soil during pregnancy, controlling
      for infant sex, maternal race, mother's age, and gestational weeks at delivery.
      There is some indication that Hg has a slightly higher importance in the third
      and fourth months of pregnancy, while As has a more uniform effect over all the
      months with a suggestion of a slight increase in risk in later months. 

PMID- 24888619
TI  - Comparative effectiveness of ACC-deaminase and/or nitrogen-fixing rhizobacteria
      in promotion of maize (Zea mays L.) growth under lead pollution.
AB  - Lead (Pb) pollution is appearing as an alarming threat nowadays. Excessive Pb
      concentrations in agricultural soils result in minimizing the soil fertility and
      health which affects the plant growth and leads to decrease in crop production.
      Plant growth promoting rhizobacteria (PGPR) are beneficial bacteria which can
      protect the plants against many abiotic stresses, and enhance the growth. The
      study aimed to identify important rhizobacterial strains by using the 1
      aminocyclopropane-1-carboxylate (ACC) enrichment technique and examine their
      inoculation effects in the growth promotion of maize, under Pb pollution. A pot
      experiment was conducted and six rhizobacterial isolates were used. Pb was added
      to 2 kg soil in each pot (with 4 seeds/pot) using Pb(NO3)2 at the rate of 0, 100,
      200, 300, and 400 mg kg(-1) Pb with three replications in completely randomized
      design. Rhizobacterial isolates performed significantly better under all Pb
      levels, i.e., 100 to 400 Pb mg kg(-1) soil, compared to control. Comparing the
      efficacy of the rhizobacterial isolates under different Pb levels, rhizobacterial
      isolates having both ACC-deaminase and nitrogen-fixing activities (AN8 and AN12)
      showed highest increase in terms of the physical, chemical and enzymatic growth
      parameters of maize, followed by the rhizobacterial isolates having ACC-deaminase
      activity only (ACC5 and ACC8), and then the nitrogen-fixing rhizobia (Azotobacter
      and RN5). However, the AN8 isolate showed maximum efficiency, and highest shoot
      and root length (14.2 and 6.1 cm), seedling fresh and dry weights (1.91 and 0.14
      g), chlorophyll a, b, and carotenoids (24.1, 30.2 and 77.7 MUg/l), protein (0.82
      mg/g), proline (3.42 MUmol/g), glutathione S-transferase, peroxidase and catalase
      (12.3, 4.2 and 7.2 units/mg protein), while the lowest Pb uptake in the shoot and
      root (0.83 and 0.48 mg/kg) were observed under this rhizobial isolate at the
      highest Pb level (i.e., 400 Pb mg kg(-1) soil). The results revealed that PGPR
      significantly decreases the deleterious effects of Pb pollution and increases the
      maize growth under all Pb concentrations, i.e., 100-400 Pb mg kg(-1) soil. PGPR
      chelate the Pb in the soil, and ultimately influence its bioavailability, release
      and uptake. The PGPR having both ACC-deaminase and nitrogen-fixing abilities are
      more effective and resistive against Pb pollution than PGPR having either ACC
      deaminase or nitrogen-fixing activity alone. The ACC enrichment technique is an
      efficient approach to select promising PGPR.

PMID- 24888620
TI  - Copper distribution in surface and subsurface soil horizons.
AB  - The horizons of four natural soils were treated with Cu(2+) in an acid medium to
      study the retention capacity of Cu. The possible mineralogical changes arising
      because of the treatment were also studied. The soil properties and
      characteristics with the greatest influence on the metal retention and its
      distribution among the different soil fractions were determined. Crystalline
      phases of each horizon were determined by X-ray diffraction (XDR). The
      morphology, structural distribution and particle chemical composition of soil
      samples were investigated using field emission scanning electron microscopy. Cu
      distribution in the different geochemical phases of the soil was studied using a
      sequential extraction. The treatment led to an increase in the amorphous phases
      and the formation of new crystalline phases, such as rouaite (Cu2(NO3)(OH)3) and
      nitratine (NaNO3). Cu was also found superficially sorbed on amorphous hydroxy
      compounds of Fe that interact with albite, muscovite and gibbsite, and also on
      spherical and curved particles of aluminium clays. The largest amount of Cu
      retained was in an exchangeable form, and the smallest amount associated with the
      crystalline Fe oxides and residual fraction. In the surface horizons, the
      predominant Cu retention process is complexation in organomineral associations,
      while in the subsurface horizons it is adsorption.

PMID- 24888621
TI  - A national reconnaissance for selected organic micropollutants in sediments on
      French territory.
AB  - To collect a large data set regarding the occurrence of organic substances in
      sediment, this study presents the examination of 20 micropollutants, as a
      national survey. The list of target compounds contains two alkylphenols, three
      polycyclic aromatic hydrocarbons (PAHs) not commonly included in monitoring
      programmes, six pesticides or metabolites, five pharmaceutical compounds, two
      hormones, one UV filter and bisphenol A. The selective and sensitive analytical
      methods, based on quick, easy, cheap, effective, rugged, and safe (QuEChERS)
      sample preparation followed by liquid chromatography-tandem mass spectrometry (LC
      MS/MS) or gas chromatography-time-of-flight mass spectrometry (GC-ToF-MS), allow
      the quantification at limits comprised between 0.5 and 23 ng/g, depending on the
      compound. The paper summarizes the analytical results from 154 sampling points.
      Of the 20 target compounds, 9 were determined at least once, and the sediments
      contained a maximum of 7 substances. The most frequently detected were PAHs
      (frequency, 77 %; max., 1,400 ng/g). The pharmaceutical compounds, hormones and
      pesticides were rarely detected in the samples; the most frequently detected was
      carbamazepine (frequency, 6 %; max., 31 ng/g). In some cases, the levels of PAHs
      and bisphenol A exceed the predicted no-effect concentration (PNEC) values.

PMID- 24888622
TI  - Assessment of the water self-purification capacity on a river affected by organic
      pollution: application of chemometrics in spatial and temporal variations.
AB  - Water pollution caused by organic matter is a major global problem which requires
      continuous evaluation. Multivariate statistical analysis was applied to assess
      spatial and temporal changes caused by natural and anthropogenic phenomena along
      Potrero de los Funes River. Cluster analysis (CA), principal component analysis
      (PCA) and analysis of variance (ANOVA) were applied to a data set collected
      throughout a period of 3 years (2010-2012), which monitored 22 physical, chemical
      and biological parameters. Content of dissolved oxygen in water and biochemical
      oxygen demand in a watercourse are indicators of pollution caused by organic
      matter. For this reason, the Streeter-Phelps model was used to evaluate the water
      self-purification capacity. Hierarchical cluster analysis grouped the sampling
      sites based on the similarity of water quality characteristics. PCA resulted in
      two latent factors explaining 75.2 and 17.6 % of the total variance in water
      quality data sets. Multidimensional ANOVA suggested that organic pollution is
      mainly due to domestic wastewater run-offs and anthropogenic influence as a
      consequence of increasing urbanization and tourist influx over the last years.
      Besides, Streeter-Phelps parameters showed a low reaeration capacity before dam
      with low concentration of dissolved oxygen. Furthermore, self-purification
      capacity loss was correlated with the decrease of the Benthic Index. This
      measurement suggested that biological samplings complement the physical-chemical
      analysis of water quality.

PMID- 24888623
TI  - Classification and identification of metal-accumulating plant species by cluster
      analysis.
AB  - Identification and classification of metal-accumulating plant species is
      essential for phytoextraction. Cluster analysis is used for classifying
      individuals based on measured characteristics. In this study, classification of
      plant species for metal accumulation was conducted using cluster analysis based
      on a practical survey. Forty plant samples belonging to 21 species were collected
      from an ancient silver-mining site. Five groups such as hyperaccumulator,
      potential hyperaccumulator, accumulator, potential accumulator, and normal
      accumulating plant were graded. For Cd accumulation, the ancient silver-mining
      ecotype of Sedum alfredii was treated as a Cd hyperaccumulator, and the others
      were normal Cd-accumulating plants. For Zn accumulation, S. alfredii was
      considered as a potential Zn hyperaccumulator, Conyza canadensis and Artemisia
      lavandulaefolia were Zn accumulators, and the others were normal Zn-accumulating
      plants. For Pb accumulation, S. alfredii and Elatostema lineolatum were potential
      Pb hyperaccumulators, Rubus hunanensis, Ajuga decumbens, and Erigeron annuus were
      Pb accumulators, C. canadensis and A. lavandulaefolia were potential Pb
      accumulators, and the others were normal Pb-accumulating plants. Plant species
      with the potential for phytoextraction were identified such as S. alfredii for Cd
      and Zn, C. canadensis and A. lavandulaefolia for Zn and Pb, and E. lineolatum, R.
      hunanensis, A. decumbens, and E. annuus for Pb. Cluster analysis is effective in
      the classification of plant species for metal accumulation and identification of
      potential species for phytoextraction.

PMID- 24888625
TI  - Novel and selective detection of Tabun mimics.
AB  - Detection of nerve agent-related molecules based on BODIPY-salicylaldehyde oxime
      conjugation was studied. Fluorescence intensity of the B-SAL-OXIME species
      increases in the presence of DECP, whereas it decreases in the presence of DCP
      and DEMP (limit of detection = 997 nM). Benzonitrile formation in the novel
      fluorescent B-SAL-OXIME system was elucidated using model substrates. 

PMID- 24888624
TI  - Retinoblastoma (RB1) pocket domain mutations and promoter hyper-methylation in
      head and neck cancer.
AB  - BACKGROUND: The RB1 gene plays a pivotal role in cell cycle regulation. In this
      case-control study we searched for alterations in the RB1 pocket domain and its
      promoter region in head and neck cancer (HNC) patients in the Pakistani
      population. METHODS: For germline mutation analyses, 380 blood samples from HNC
      patients and 350 blood samples from control individuals were included. Polymerase
      chain reaction (PCR) and single strand conformational polymorphism (SSCP) assays,
      followed by sequence analyses, were used for the RB1 pocket domain mutation
      screens. For the RB1 promoter methylation screens, 72 HNC tumor samples along
      with adjacent uninvolved tissues were tested using a methylation-specific
      polymerase chain reaction (MSP) assay. RESULTS: RB1 (pocket domain and spacer
      region) sequence analysis revealed one frameshift and seven non-synonymous
      missense mutations. The frequency of missense mutations in exon 14, i.e., g76474C
      > T, g76475G > C and g76476A > G, resulting in Arg455Ser, was found to be highest
      (0.10). Missense mutations g76467G > C (exon14), g76468T > C (exon14), g77041A >
      T and g77043A > T (exon 16), when analyzed via Alamut biosoftware version 2.0,
      were found to be present in highly conserved amino acids with Align GVGD scores
      C15 (GV: 0.00-GD: 21.82), C65 (GV: 0.00-GD: 83.33) and C65 (GV: 0.00-GD: 98.69),
      respectively. These missense mutations were found to be deleterious by SIFT
      score: 0.00 (median 3.64). RB1 promoter methylation analysis revealed that 16% of
      its cytosines (3% in CpG) were methylated in the HNC tumor samples. CONCLUSION:
      Our findings indicate that both genetic and epigenetic RB1 changes may contribute
      to the pathogenesis of HNC in the Pakistani population.

PMID- 24888626
TI  - Pneumomediastinum secondary to blunt neck trauma in children: a case report.

PMID- 24888627
TI  - Indirect photochemistry in sunlit surface waters: photoinduced production of
      reactive transient species.
AB  - This paper gives an overview of the main reactive transient species that are
      produced in surface waters by sunlight illumination of photoactive molecules
      (photosensitizers), such as nitrate, nitrite, and chromophoric dissolved organic
      matter (CDOM). The main transients (OH, CO3(-) , (1)O2, and CDOM triplet states)
      are involved in the indirect phototransformation of a very wide range of
      persistent organic pollutants in surface waters.

PMID- 24888628
TI  - Critical considerations on the utility of 18F-fluoro-2-deoxy-D-glucose positron
      emission tomography/computed tomography for posttreatment restaging of the bone
      marrow in diffuse large B-cell lymphoma.

PMID- 24888630
TI  - Macroporous reversed-phase separation of proteins combined with reversed-phase
      separation of phosphopeptides and tandem mass spectrometry for profiling the
      phosphoproteome of MDA-MB-231 cells.
AB  - A new method of combining macroporous RP (mRP) protein fractionation with RPLC
      peptide separation MS/MS is reported for profiling the phosphoproteome of a
      complex sample. In this method, an mRP-C18 column was used to fractionate the
      proteins from a whole cell lysate of a breast cancer cell line, MDA-MB-231, into
      38 fractions. Each fraction was subjected to tryptic digestion, sequential
      phosphopeptide enrichment by immobilized metal ion affinity chromatography and
      titanium dioxide (TiO2 ), followed by capillary RPLC-MS/MS analysis. For
      comparison, the conventional method of using strong cation exchange RPLC
      separation of peptides combined with MS/MS was also used for analyzing the
      phosphoproteome. Replicate experiments by the mRP-RPLC method identified 1585
      distinct phosphoproteins with 4519 phosphopeptides, compared to 1585
      phosphoproteins with 4297 phosphopeptides by strong cation exchange RPLC, with a
      total of 1947 phosphoproteins and 6278 phosphopeptides identified from the
      combined results. While the two methods have similar ability in the
      identification of the phosphoproteome, they produce complementary information.
      The phosphoproteins identified in this study, including 67 novel phosphorylation
      sites from 56 breast cancer related proteins, can serve as the entry point for
      future validation with biological implications in breast cancer. The MS
      proteomics data have been deposited to the ProteomeXchange Consortium via the
      PRIDE partner repository with the dataset identifier PXD000948 and DOI
      10.6019/PXD000948. 

PMID- 24888631
TI  - Current status of cord blood banking during first two years of 'National
      Government-Assigned Public Cord Blood Banks Operation' in Korea.
AB  - Cord blood (CB) has become a viable stem cell source for hematopoietic stem cell
      transplantation (HSCT), and public cord blood banks (CBBs) have been established
      to manage donated cord blood units (CBUs) for unrelated HSCT. As the potential
      uses for CB continue to grow, there is a global tendency to encourage public
      CBBs. The aim of this study was to investigate the current status of public CBBs
      that were designated and supported by the Korean national government. We analyzed
      6,168 CBUs preserved at the 3 Government-Assigned Public CBBs during their first
      two years of operation (2012-2013) and the standard operating procedures for CB
      processing at each CBB. CBU inventories at ALLCORD, Catholic HSC Bank and Fatima
      Public CBB were 4,022, 1,207 and 939 units, respectively. Total nucleated cell
      (TNC) counts per unit were 11.0 * 10(8) at ALLCORD, 10.7 * 10(8) at Fatima and
      9.8 * 10(8) at Catholic, and all far exceeded the requirement for
      cryopreservation under the law (7.0 * 10(8)). CD34(+) cell counts and % were as
      follows: 3.5 * 10(6) (0.31 %) in ALLCORD, 2.2 * 10(6) (0.20 %) in Fatima and 2.2
      * 10(6) (0.22 %) in Catholic. All the three banks observed the 'CB Act' in
      dealing with CBUs, including collection, processing, laboratory tests and
      cryopreservation. Government supported and strictly law-abiding public CBBs in
      Korea have considerable CBU inventories of high quality in terms of efficacy and
      safety. Legislation and accompanying government-support will be helpful for
      establishing CB standardization, vitalizing CBT and improving clinical outcomes.

PMID- 24888632
TI  - New ab initio potential energy surfaces for the ro-vibrational excitation of
      OH(X(2)Pi) by He.
AB  - We present a new set of three-dimensional potential energy surfaces (PES) for the
      OH(X(2)Pi)-He van der Waals system, which explicitly takes into account the OH
      vibrational motion. Ab initio calculations of the OH-He PES were carried out
      using the open-shell single- and double-excitation coupled cluster approach with
      non-iterative perturbational treatment of triple excitations [RCCSD(T)]. The
      augmented correlation-consistent aug-cc-pVXZ (X = Q, 5, 6) basis sets were
      employed, and the energies obtained were then extrapolated to the complete basis
      set (CBS) limit. Integral and differential cross sections (ICS and DCS), and
      thermal rate coefficients for the rotational excitation in OH + He collisions
      were calculated using the new PES, and compared with available experimental
      results. Experimental and theoretical results were found to be in a very good
      agreement. The newly constructed PES reproduces the available experimental
      results for OH(X(2)Pi, v = 0, 1) + He collisions better than the previously
      available two-dimensional PESs, which were constructed using a fixed OH bond
      distance. Our work provides the first RCCSD(T) PES for future anticipated
      experiments in OH(X(2)Pi, v >= 0) + He collisions. 

PMID- 24888629
TI  - The effectiveness of service delivery initiatives at improving patients' waiting
      times in clinical radiology departments: a systematic review.
AB  - We reviewed the literature for the impact of service delivery initiatives (SDIs)
      on patients' waiting times within radiology departments. We searched MEDLINE,
      EMBASE, CINAHL, INSPEC and The Cochrane Library for relevant articles published
      between 1995 and February, 2013. The Cochrane EPOC risk of bias tool was used to
      assess the risk of bias on studies that met specified design criteria. Fifty
      seven studies met the inclusion criteria. The types of SDI implemented included
      extended scope practice (ESP, three studies), quality management (12 studies),
      productivity-enhancing technologies (PETs, 29 studies), multiple interventions
      (11 studies), outsourcing and pay-for-performance (one study each). The
      uncontrolled pre- and post-intervention and the post-intervention designs were
      used in 54 (95%) of the studies. The reporting quality was poor: many of the
      studies did not test and/or report the statistical significance of their results.
      The studies were highly heterogeneous, therefore meta-analysis was inappropriate.
      The following type of SDIs showed promising results: extended scope practice;
      quality management methodologies including Six Sigma, Lean methodology, and
      continuous quality improvement; productivity-enhancing technologies including
      speech recognition reporting, teleradiology and computerised physician order
      entry systems. We have suggested improved study design and the mapping of the
      definitions of patient waiting times in radiology to generic timelines as a
      starting point for moving towards a situation where it becomes less restrictive
      to compare and/or pool the results of future studies in a meta-analysis.

PMID- 24888633
TI  - Association between eating disorders and migraine may be explained by major
      depression.
AB  - OBJECTIVE: The association between eating disorders and migraine remains unclear.
      METHOD: We identified women with lifetime diagnoses of anorexia nervosa (AN) (N =
      55) and bulimia nervosa (BN) (N = 60) and their co-twins from the FinnTwin16
      cohort born in 1975-1979 (N = 2,825 women). Eating disorder and major depressive
      disorder (MDD) diagnoses were obtained from clinical interviews and data on
      migraine by self-report questionnaire. The women with eating disorders were
      compared with their unaffected co-twins and with unrelated women from the same
      birth cohorts. RESULTS: The prevalence of migraine was 12% in the general female
      population, but 22% for both AN and BN (odds ratio 2.0, p = .04). The prevalence
      of MDD was high in women with an eating disorder (42%). MDD was strongly
      associated with migraine (odds ratio 3.0, p < .0001) and explained the
      association between eating disorders and migraine. The highest migraine
      prevalence (36%) was found in women with both an eating disorder and MDD.
      Pairwise twin analyses also supported the clustering of migraine, MDD and eating
      disorders. DISCUSSION: Women with a lifetime diagnosis of an eating disorder were
      twice as likely to report a history of migraine as unrelated women from the same
      cohort; this relationship was explained by comorbid MDD.

PMID- 24888634
TI  - Laboratory evolution of adenylyl cyclase independent learning in Drosophila and
      missing heritability.
AB  - Gene interactions are acknowledged to be a likely source of missing heritability
      in large-scale genetic studies of complex neurological phenotypes. However,
      involvement of rare variants, de novo mutations, genetic lesions that are not
      easily detected with commonly used methods and epigenetic factors also are
      possible explanations. We used a laboratory evolution study to investigate the
      modulatory effects of background genetic variation on the phenotypic effect size
      of a null mutation with known impact on olfactory learning. To accomplish this,
      we first established a population that contained variation at just 23 loci and
      used selection to evolve suppression of the learning defect seen with null
      mutations in the rutabaga adenylyl cyclase. We thus biased the system to favor
      relatively simplified outcomes by choosing a Mendelian trait and by restricting
      the genetic variation segregating in the population. This experimental design
      also assures that the causal effects are among the known 23 segregating loci. We
      observe a robust response to selection that requires the presence of the 23
      variants. Analyses of the underlying genotypes showed that interactions between
      more than two loci are likely to be involved in explaining the selection
      response, with implications for the missing heritability problem. 

PMID- 24888635
TI  - Fermentation conditions influence the fatty acid composition of the membranes of
      Lactobacillus reuteri I5007 and its survival following freeze-drying.
AB  - Lactobacillus reuteri I5007 has well-documented adhesion properties and health
      benefits. Future industrial use of Lact. reuteri I5007 will require the
      development of effective fermentation procedures and high bacterial survival
      following drying. Therefore, this study was conducted to determine the impact of
      altering fermentation pH and temperature on the fatty acid composition of the
      bacterial membranes and subsequent survival of Lact. reuteri I5007 following
      freeze-drying. Initially, a response surface methodology was used to determine
      the optimal fermentation pH (5.7) and temperature (37 degrees C), with regard to
      producing the maximum number of Lact. reuteti I5007 cells. However, when
      subjected to the optimal fermentation pH and temperature (control treatment), the
      subsequent survival of Lact. reuteri I5007 following freeze-drying was only
      12.95%. Growth at a higher temperature (47 degrees C) or at a neutral pH (pH 6.7)
      significantly increased the survival of Lact. reuteri I5007 following freeze
      drying compared with the control. In contrast, an acidic pH (pH 4.7), or cold (27
      degrees C) and extremely cold (4 degrees C) temperatures during fermentation
      significantly reduced Lact. reuteri I5007 survival following freeze-drying. The
      fatty acid composition of the membranes of Lact. reuteri I5007 was altered by the
      different fermentation conditions tested. An increase in the ratio of unsaturated
      fatty acids (UFA) to saturated fatty acids (SFA) in the bacterial membrane was
      associated with higher survival of Lact. reuteri I5007. In conclusion, it appears
      that the use of a higher temperature (47 degrees C) or neutral pH (6.7) during
      fermentation resulted in increased survival of Lact. reuteri I5007 following
      freeze-drying. Significance and impact of the study: In this study, we found that
      a higher fermentation temperature or a neutral pH, rather than cold or acidic
      conditions, leads to increased survival of Lact. reuteri I5007 during subsequent
      freeze-drying. This finding has important implications for the future industrial
      production of this probiotic strain.

PMID- 24888637
TI  - New method for viewing Krehbiel flow by polymethylmethacrylate particles
      suspended in fluorescein solution.
AB  - PURPOSE: To investigate the changes in the tear flow velocities caused by ageing.
      METHODS: Ninety-nine subjects (41 men, mean age 48.3 +/- 20.7 years) were
      recruited from the Department of Ophthalmology of the Ehime University Hospital.
      None of the subjects had serious abnormalities of the external surface of the
      eye. The Krehbiel flow of tears was determined by 40-MUm polymethylmethacrylate
      (PMMA) beads suspended in a fluorescein sodium solution (PPF). The movement of
      the beads was video recorded through a slit-lamp during normal blinking. The flow
      of the beads was determined with a Motion ANALYZER((r)) software (KEYENCE Co.,
      Osaka, Japan). The velocity of the beads in young age, 20-40 years, middle age,
      41-60 years and old age, >=61 years, groups was determined. RESULTS: The equation
      describing the velocity (mm/second) of the PMMA particles as a function of age in
      the lower tear meniscus measured in the direction of the lacrimal punctum was Y =
      2.49-0.04X, where Y = velocity and X = age (r(2) = 0.214; p < 0.0001). For the
      upper meniscus, the equation was Y = 4.83-0.05X (r(2) = 0.195, p < 0.0001). The
      average velocity was 0.70 +/- 1.66 mm/second in the lower and 2.16 +/- 1.93
      mm/second in the upper tear meniscus (p < 0.0001). The particle velocity
      decreased significantly with increasing age, but no significant difference
      between the male and female groups except for the lower tear meniscus when all
      subjects were analysed. CONCLUSION: The PPF technique is a simple method of
      examining Krehbiel flow of tears and may be used for evaluating functional
      nasolacrimal duct obstruction quantitatively.

PMID- 24888636
TI  - Mechanisms of blindness: animal models provide insight into distinct CRX
      associated retinopathies.
AB  - BACKGROUND: The homeodomain transcription factor CRX is a crucial regulator of
      mammalian photoreceptor gene expression. Mutations in the human CRX gene are
      associated with dominant inherited retinopathies Retinitis Pigmentosa (RP), Cone
      Rod Dystrophy (CoRD), and Leber Congenital Amaurosis (LCA), of varying severity.
      In vitro and in vivo assessment of mutant CRX proteins have revealed pathogenic
      mechanisms for several mutations, but no comprehensive mutation-disease
      correlation has yet been reported. RESULTS: Here we describe four different
      classes of disease-causing CRX mutations, characterized by mutation type,
      pathogenetic mechanism, and the molecular activity of the mutant protein: (1)
      hypomorphic missense mutations with reduced DNA binding, (2) antimorphic missense
      mutations with variable DNA binding, (3) antimorphic frameshift/nonsense
      mutations with intact DNA binding, and (4) antimorphic frameshift mutations with
      reduced DNA binding. Mammalian models representing three of these classes have
      been characterized. CONCLUSIONS: Models carrying Class I mutations display a mild
      dominant retinal phenotype and recessive LCA, while models carrying Class III and
      IV mutations display characteristically distinct dominant LCA phenotypes. These
      animal models also reveal unexpected pathogenic mechanisms underlying CRX
      associated retinopathies. The complexity of genotype-phenotype correlation for
      CRX-associated diseases highlights the value of developing comprehensive "true-to
      disease" animal models for understanding pathologic mechanisms and testing novel
      therapeutic approaches.

PMID- 24888639
TI  - Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with
      screening magnetic resonance imaging.
AB  - BACKGROUND: Female survivors of pediatric Hodgkin lymphoma (HL) who have received
      chest radiotherapy are at increased risk of breast cancer. Guidelines for early
      breast cancer screening among these survivors are based on little data regarding
      clinical outcomes. This study reports outcomes of breast cancer screening with
      MRI and mammography (MMG) after childhood HL. METHODS: We evaluated the results
      of breast MRI and MMG screening among 96 female survivors of childhood HL treated
      with chest radiotherapy. Outcomes measured included imaging sensitivity and
      specificity, breast cancer characteristics, and incidence of additional imaging
      and breast biopsy. RESULTS: Median age at first screening was 30 years, and the
      median number of MRI screening rounds was 3. Ten breast cancers were detected in
      9 women at a median age of 39 years (range, 24-43 years). Half were invasive and
      half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15
      mm), and none had lymph node involvement. Sensitivity and specificity of the
      screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively;
      MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%,
      respectively. All invasive tumors were detected by MRI. Additional investigations
      were required in 52 patients, (54%), and 26 patients (27%) required breast
      biopsy, with 10 patients requiring more than 1 biopsy. CONCLUSIONS: Screening
      including breast MRI with MMG has high sensitivity and specificity in pediatric
      HL survivors, with breast cancers detected at an early stage, although it is
      associated with a substantial rate of additional investigations.

PMID- 24888638
TI  - Enzyme structure captures four cysteines aligned for disulfide relay.
AB  - Thioredoxin superfamily proteins introduce disulfide bonds into substrates,
      catalyze the removal of disulfides, and operate in electron relays. These
      functions rely on one or more dithiol/disulfide exchange reactions. The
      flavoenzyme quiescin sulfhydryl oxidase (QSOX), a catalyst of disulfide bond
      formation with an interdomain electron transfer step in its catalytic cycle,
      provides a unique opportunity for exploring the structural environment of
      enzymatic dithiol/disulfide exchange. Wild-type Rattus norvegicus QSOX1 (RnQSOX1)
      was crystallized in a conformation that juxtaposes the two redox-active di
      cysteine motifs in the enzyme, presenting the entire electron-transfer pathway
      and proton-transfer participants in their native configurations. As such a state
      cannot generally be enriched and stabilized for analysis, RnQSOX1 gives
      unprecedented insight into the functional group environments of the four
      cysteines involved in dithiol/disulfide exchange and provides the framework for
      analysis of the energetics of electron transfer in the presence of the bound
      flavin adenine dinucleotide cofactor. Hybrid quantum mechanics/molecular
      mechanics (QM/MM) free energy simulations based on the X-ray crystal structure
      suggest that formation of the interdomain disulfide intermediate is highly
      favorable and secures the flexible enzyme in a state from which further electron
      transfer via the flavin can occur. 

PMID- 24888640
TI  - Decline in intrahepatic cccDNA and increase in immune cell reactivity after 12
      weeks of antiviral treatment were associated with HBeAg loss.
AB  - Viral load reduction facilitates recovery of antiviral T-cell responses. Dynamic
      alterations in intrahepatic viraemia clearance and immune cell reactivity during
      the early phase of nucleoside analogue (NA) therapy and the impact of these
      changes on HBeAg seroconversion are unknown. Fifteen HBeAg-positive chronic
      hepatitis B (CHB) patients were treated with adefovir dipivoxil. T-cell
      reactivity to HBV core and surface antigens were tested using ELISPOT assay from
      baseline to week 48 post-treatment (at 4-week intervals). Before and at week 12
      of treatment, paired liver biopsies were analysed for intrahepatic HBV-DNA and
      cccDNA via real-time fluorescent PCR. In situ detection of CD4(+) , CD8(+) T
      cells and NK cells was analysed by immunohistochemistry. With viral load
      reduction, HBV-specific IFN-gamma-producing CD4(+) T cells in patients with HBeAg
      loss were greatly enhanced and reached the highest level at week 12, with further
      increase observed between week 36 and week 48. After 12 weeks of treatment, total
      intrahepatic HBV-DNA and cccDNA had significantly decreased; however, there was
      no difference in the viral loads or extent of reduction between patients with and
      without HBeAg loss. Paralleling reduction in viral load, intrahepatic CD8(+) T
      lymphocytes increased in patients with HBeAg loss compared with baseline values.
      Only one patient without HBeAg loss exhibited similar results. Increased immune
      cells were observed in certain patients along with reduced hepatic viral loads
      during the second phase of HBV-DNA decline, which could promote the recovery of
      antiviral immunity and facilitate HBeAg loss. 

PMID- 24888641
TI  - Clinical, anatomical, and technical risk factors for postoperative pacemaker or
      defibrillator lead perforation with particular focus on myocardial thickness.
AB  - BACKGROUND: Postoperative lead perforation is a life-threatening complication of
      cardiac pacing. Identification of precipitating factors for this serious
      complication may help to anticipate a specific risk profile and to minimize the
      incidence. METHODS: We conducted a retrospective tertiary referral center
      analysis to clarify clinical, anatomical, and technical characteristics related
      to pacemaker (PM) and cardioverter/defibrillator lead perforation. We examined
      the baseline characteristics and the symptoms. In a subgroup, we investigated the
      myocardial thickness on contrast-enhanced cardiac computed tomography. RESULTS:
      We enrolled 26 patients. Female gender appears to put patients at slightly
      increased risk for lead perforation. In a majority active fixation leads were
      used. Symptoms occurred in 72%. Pericardial effusion and tamponade were present
      in 38% and 19%, respectively. Sensing was compromised in 65%. A high pacing
      threshold or exit block occurred in 92%. Myocardial thickness did not differ
      between patients with or without perforation. In 96%, the perforation was treated
      by transvenous withdrawal. CONCLUSION: Chest pain, phrenic stimulation, bad
      sensing, or exit block early after PM implantation must prompt radiological and
      echocardiographic evaluation. A missing pericardial effusion particularly late
      after implantation does not rule out a perforation. Especially active fixating
      leads have a higher risk of perforation. With cardiac surgery in standby
      transvenous withdrawal is a safe way to treat lead perforation.

PMID- 24888642
TI  - Minimising perinatal mortality in twins: planned birth at 38 weeks of gestation
      for dichorionic and 36 weeks of gestation for monochorionic twins.

PMID- 24888643
TI  - Impact of routine reporting of estimated glomerular filtration rate using the CKD
      EPI formula in a community population: A cross-sectional cohort study.
AB  - AIM: Most laboratories are moving to report estimated glomerular filtration rates
      (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      formula. However, data on the prevalence of chronic kidney disease (CKD) in the
      population and its economic impact have to date been modelled using data derived
      from the modification of diet in renal disease (MDRD) equation. Evaluating the
      impact of CKD-EPI on prevalence has important implications for referral patterns
      and health expenditure. METHODS: eGFR were calculated from 2 295313 creatinine
      results from 833334 patients using the MDRD and CKD-EPI formulae. The proportion
      of patients in each CKD stage was determined and annual rates of change of eGFR
      in patients assigned to a new CKD stage compared with their previous CKD stage
      calculated. The effects of age on eGFR were assessed. RESULTS: Reporting of eGFR
      using the CKD-EPI equation reduced the prevalence of CKD stages III-V from 9.2%
      to 7.6%. A total of 181126 patients were reclassified using CKD-EPI with 171298
      changing to a better CKD stage. Reclassification rates were highest in CKD stages
      II and III. Patients reclassified from stage III to II tended to be younger or
      female. eGFR declines rapidly after the age of 60. CONCLUSIONS: Introduction of
      routine eGFR reporting using the CKD-EPI formula will reduce the population
      prevalence of CKD. CKD-EPI reporting better identifies patients at risk of
      further decline in renal function. Improvement in the classification should
      reduce unnecessary costs related to surveillance and referral. The impact of
      ageing on renal function should be appreciated.

PMID- 24888644
TI  - Energy availability and the female athlete triad in elite endurance athletes.
AB  - The female athlete triad (Triad), links low energy availability (EA), with
      menstrual dysfunction (MD), and impaired bone health. The aims of this study were
      to examine associations between EA/MD and energy metabolism and the prevalence of
      Triad-associated conditions in endurance athletes. Forty women [26.2 +/- 5.5
      years, body mass index (BMI) 20.6 +/- 2.0 kg/m(2), body fat 20.0 +/- 3.0%],
      exercising 11.4 +/- 4.5 h/week, were recruited from national teams and
      competitive clubs. Protocol included gynecological examination; assessment of
      bone health; indirect respiratory calorimetry; diet and exercise measured 7 days
      to assess EA; eating disorder (ED) examination; blood analysis. Subjects with
      low/reduced EA (< 45 kcal/kg FFM/day), had lower resting metabolic rate (RMR)
      compared with those with optimal EA [28.4 +/- 2.0 kcal/kg fat-free mass (FFM)/day
      vs 30.5 +/- 2.2 kcal/kg FFM/day, P < 0.01], as did subjects with MD compared with
      eumenorrheic subjects (28.6 +/- 2.4 kcal/kg FFM/day vs 30.2 +/- 1.8 kcal/kg
      FFM/day, P < 0.05). 63% had low/reduced EA, 25% ED, 60% MD, 45% impaired bone
      health, and 23% had all three Triad conditions. 53% had low RMR, 25%
      hypercholesterolemia, and 38% hypoglycemia. Conclusively, athletes with
      low/reduced EA and/or MD had lowered RMR. Triad-associated conditions were common
      in this group of athletes, despite a normal BMI range. The high prevalence of ED,
      MD, and impaired bone health emphasizes the importance of prevention, early
      detection, and treatment of energy deficiency.

PMID- 24888645
TI  - Oxytocin: its mechanism of action and receptor signalling in the myometrium.
AB  - Oxytocin is a nonapeptide hormone that has a central role in the regulation of
      parturition and lactation. In this review, we address oxytocin receptor (OTR)
      signalling and its role in the myometrium during pregnancy and in labour. The OTR
      belongs to the rhodopsin-type (Class 1) of the G-protein coupled receptor
      superfamily and is regulated by changes in receptor expression, receptor
      desensitisation and local changes in oxytocin concentration. Receptor activation
      triggers a number of signalling events to stimulate contraction, primarily by
      elevating intracellular calcium (Ca(2+) ). This includes inositol-tris-phosphate
      mediated store calcium release, store-operated Ca(2+) entry and voltage-operated
      Ca(2+) entry. We discuss each mechanism in turn and also discuss Ca(2+) 
      independent mechanisms such as Ca(2+) sensitisation. Because oxytocin induces
      contraction in the myometrium, both the activation and the inhibition of its
      receptor have long been targets in the management of dysfunctional and preterm
      labours, respectively. We discuss current and novel OTR agonists and antagonists
      and their use and potential benefit in obstetric practice. In this regard, we
      highlight three clinical scenarios: dysfunctional labour, postpartum haemorrhage
      and preterm birth. 

PMID- 24888650
TI  - Dermatological manifestations of hepatitis C virus infection in Saudi Arabia.
AB  - The Saudi Ministry of Health data indicates that almost 32% of viral hepatitis
      cases were caused by hepatitis C virus (HCV). It has been widely reported that
      chronic HCV infection is associated with and may trigger or exacerbate many skin
      manifestations in 20-40% of patients visiting dermatologists. The most commonly
      encountered dermatological manifestations of HCV infection globally include mixed
      cryoglobulinemia, porphyria cutanea tarda, cutaneous and/or oral lichen planus,
      urticaria, pruritus, thrombocytopenic purpura, and psoriasis. The current article
      indicates that HCV infection is increasing in Saudi Arabia and approximately 12%
      of the reported dermatological manifestations are caused by HCV infection. We
      recommend the urgent need for large-scale, case-control studies to understand the
      impact of HCV infection in patients with skin disease. 

PMID- 24888649
TI  - Biological ingredient analysis of traditional Chinese medicine preparation based
      on high-throughput sequencing: the story for Liuwei Dihuang Wan.
AB  - Although Traditional Chinese Medicine (TCM) preparations have long history with
      successful applications, the scientific and systematic quality assessment of TCM
      preparations mainly focuses on chemical constituents and is far from
      comprehensive. There are currently only few primitive studies on assessment of
      biological ingredients in TCM preparations. Here, we have proposed a method, M
      TCM, for biological assessment of the quality of TCM preparations based on high
      throughput sequencing and metagenomic analysis. We have tested this method on
      Liuwei Dihuang Wan (LDW), a TCM whose ingredients have been well-defined. Our
      results have shown that firstly, this method could determine the biological
      ingredients of LDW preparations. Secondly, the quality and stability of LDW
      varies significantly among different manufacturers. Thirdly, the overall quality
      of LDW samples is significantly affected by their biological contaminations. This
      novel strategy has the potential to achieve comprehensive ingredient profiling of
      TCM preparations. 

PMID- 24888652
TI  - Correlation between expression of miR-155 in colon cancer and serum
      carcinoembryonic antigen level and its contribution to recurrence and metastasis
      forecast.
AB  - OBJECTIVE: To analyze the correlation between expression of miR-155 in colon
      cancer tissue and serum carcinoembryonic antigen (CEA) levels, and then explore
      its contribution to forecasting recurrence and metastasis. METHODS: Eighty-four
      pairs of colon cancer specimens and their corresponding non-tumor adjacent
      tissues were collected and analyzed between March 2009 and December 2011 in
      Xiangyang Central Hospital, Xiangyang, Hubei, China. The expression of miR-155 in
      both tissues was tested using reverse transcription-polymerase chain reaction (RT
      PCR), the preoperative serum CEA level was assessed, and the postoperative serum
      CEA level was also assessed bimonthly during the follow-up period of 2 years.
      RESULTS: The expression of miR-155 in colon cancer tissue was significantly
      higher than that in normal tissues (p<0.05), it had an obvious positive
      correlation with the preoperative serum CEA levels (p<0.01), and a negative
      correlation with time of duration since the serum CEA level increased again
      postoperatively (p<0.01). The expression of miR-155 in the recurrence and
      metastasis group was significantly higher (6.06+/-3.73 times) than that in the
      non-recurrence and non-metastasis group (p<0.05). An increase in the
      postoperative serum CEA levels was significantly correlated with recurrence and
      metastasis of the tumor postoperatively. CONCLUSION: The expression of miR-155 is
      up-regulated in colon cancer tissue. A combination of miR-155 level assay in
      colon cancer tissue and the serum CEA level both pre- and postoperatively can
      afford more accurate information for diagnosis and prognosis, especially for
      predicting recurrence and metastasis postoperatively.

PMID- 24888651
TI  - Increased systemic low-grade inflammation in high altitude native rats mediated
      by adrenergic receptors.
AB  - OBJECTIVE: To compare the serum levels of inflammatory mediators in high altitude
      (HA) native rats, and to search for the possible underlying mechanism(s).
      METHODS: The study was carried out between January and April 2013. Fifty male
      rats from the same genetic pool were bred at either a HA or low altitude (LA)
      area. The study was carried out in 2 stages. In the first stage, serum levels of
      inflammatory markers, adhesive molecules, lipid profiles, catecholamines,
      magnesium (Mg+2), and lipid peroxidation were compared between theses 2 groups.
      In the second stages, inflammatory response and lipid peroxidation were analyzed
      in HA native rats after treatment with either alpha (Prazosin) or beta
      (propranolol) adrenergic blockage. RESULTS: The HA native rats showed significant
      increases in the serum levels of inflammatory cytokines, lipid profiles, as well
      as a significant increase in the urinary norepinephrine with a concomitant
      decrease in the serum levels of Mg+2 and increased lipid peroxidation. Blockage
      of the beta and alpha adrenergic receptors of the HA rats caused partial or
      complete decreases in both inflammatory and oxidative stress mediators.
      CONCLUSION: Living under HA conditions results in an increased systemic
      inflammatory reaction; an effect that is mediated through the sympathetic nervous
      system mainly via alpha-adrenergic receptors and could be attributed to low Mg+2
      levels.

PMID- 24888653
TI  - Transient elastography in hepatitis B virus infection. Liver stiffness
      discrepancy due to sampling location.
AB  - OBJECTIVE: To investigate the variability in liver stiffness (LS), measured by
      transient elastography, and determine the possible influencing factors in
      hepatitis B virus infection. METHODS: This cross-sectional study was conducted at
      the Department of Infectious Diseases, Tongji Hospital, Tongji Medical College,
      Huazhong University of Science and Technology, Wuhan, Hubei Province, China from
      March to June 2010. Three successful measurements at different sites in 123
      patients were obtained, and the LS discrepancy was calculated. The influence of
      clinical data on the discrepancy was also assessed. RESULTS: The LS discrepancy
      was 1.3 (0.2-16.5) kPa and independently increased with a fibrosis stage: 0.9
      (0.2-4.4) kPa in F0/F1, 1.5 (0.4-3.7) kPa in F2, 3.0 (0.3-9.4) kPa in F3, and 7.4
      (3.1-16.5) kPa in F4. A discrepancy >/=2 kPa was observed in 45 (36.6%) patients:
      8 (11.9%) with F0/F1, 7 (31.8%) with F2, 15 (73.7%) with F3, and 15 (100%) with
      F4. The incidence of discrepancy >/=2 kPa was only associated with fibrosis stage
      in multiple regression analysis. Discordance in fibrosis stages was observed in
      33 (26.8%) patients, and was most frequent in stage F2 (F0/F1, 10.45%; F2, 68.2%;
      F3, 36.8%; and F4, 26.7%). CONCLUSION: The LS discrepancy is common and
      associated with fibrosis stage independently. While determining the fibrosis
      stage and disease progression, LS discrepancy should be considered.

PMID- 24888654
TI  - Do not resuscitate orders in a Saudi pediatric intensive care unit.
AB  - OBJECTIVE: To determine the percentage of deaths in the pediatric intensive care
      unit (PICU) attributed to do not resuscitate (DNR) orders, and to compare our DNR
      practice with the international experience. METHODS: Retrospective chart review
      of all children less than 14 years of age who died in the PICU at King Faisal
      Specialist Hospital and Research Center, Riyadh, Saudi Arabia from January 2007
      to June 2009 (n=154). RESULTS: The main mode of death was attributed to DNR
      orders in 79 cases (51%), failed cardiopulmonary resuscitation in 60 cases (39%),
      and brain death in 15 cases (10%). Of the 79 DNR orders, 46 (58%) were related to
      withdrawal of life support measures. CONCLUSION: The DNR is the most common cause
      of death in the PICU in tertiary hospitals in Saudi Arabia. To minimize the
      suffering of the dying child, life support limitation should be considered for
      children with terminal or untreatable diseases with low chances of survival.

PMID- 24888655
TI  - Systemic lupus erythematosus in Arab children. Differences and similarities with
      different ethnicities.
AB  - OBJECTIVE: To describe systemic lupus erythematosus (SLE) features among Arab
      children, and compare with cohorts from different ethnicities. METHODS: This
      retrospective analysis of all published English literature on SLE in Arab
      children was conducted in March 2013. The percentage and frequencies of the
      clinical and laboratory features were collected, and compared between different
      Arab countries as well as Caucasian and South East Asian cohorts. RESULTS: A
      total of 560 children from 5 Arab cohorts with an average age at diagnosis of 10
      years; 7.7% of patients were diagnosed before the age of 5 years. Familial SLE
      was frequent. Most patients had major organ involvement. Renal involvement was
      diagnosed in 80%, while neuropsychiatric manifestations were seen in 30%.
      Immunosuppressive agents were commonly used. Beta cell depletion was recently
      introduced for refractory cases. The outcome of the disease could not be
      determined from the available data. However, 145 out of 300 patients had disease
      damage (52.6% Saudi and 43.9% Egyptian) with mean of 1.3 for Saudi and 0.93 for
      Egyptian. Forty patients died during the disease course due to infections and
      severe organ disease. CONCLUSION: Systemic lupus erythematosus is common in Arab
      children, particularly familial SLE. The manifestations observed in Arabs are
      comparable with previous reports. However, there is a noticeable difference in
      the damage accrual and mortality rate between Arab and Canadian studies, which
      might reflect the disease severity.

PMID- 24888656
TI  - Infants of diabetic mothers. A cohort study.
AB  - OBJECTIVE: To determine the outcome of infants born to diabetic mothers at
      Security Forces Hospital, Riyadh, Saudi Arabia, and compare the complications
      seen in these infants with infants of non-diabetic mothers. METHODS: This is a
      concurrent prospective cohort study of a population of newborn infants delivered
      at Security Forces Hospital, Riyadh, Saudi Arabia for diabetic mothers between
      January 2011 and November 2011. RESULTS: A total of 601 infants were enrolled in
      the study consisting of 319 infants of non-diabetic mothers, and 282 infants of
      diabetic mothers. Infants of diabetic mothers showed significantly higher rates
      of associated complications and prolonged hospital stay reflected in their
      admission to the neonatal intensive care when compared with infants of non
      diabetic mothers. There was no difference in rate of complications between
      infants of gestational diabetics and pre-gestational diabetics. CONCLUSION: Our
      study showed that diabetic pregnancies are associated with an increased incidence
      of neonatal complications. These seem to be related to the degree of maternal
      glycemic control. The higher rates of complications among our infants of diabetic
      mothers, particularly major congenital malformations call for those involved in
      the care of diabetic mothers to consolidate their efforts to facilitate early
      booking in specialist clinics.

PMID- 24888657
TI  - General public knowledge, preferred dosage forms, and beliefs toward medicines in
      western Saudi Arabia.
AB  - OBJECTIVE: To measure general public knowledge, source of knowledge, preferred
      dosage forms, and beliefs toward medicines. METHODS: A cross-sectional study
      design using convenience-sampling technique was used. A pre-validated
      questionnaire was designed and distributed to the general public through face-to
      face interviews. All data were analyzed, and p-values less than 0.05 were
      considered significant. The study took place in the Clinical Pharmacy Department,
      Taif University, Taif, Kingdom of Saudi Arabia between August 2012 and February
      2013 RESULTS: Nine hundred participants successfully responded to this study.
      Males represented two-thirds of the respondents (66.8%). In addition, 52% of
      respondents were of high education level. Modern (74.2%) and alternative
      medicines (88.7%) were understood by most respondents. Tablets (69.6%) and
      capsules (37.6%) represented the highest preferred dosage forms. In addition,
      physicians (66.6%) and pharmacists (46.2%) were the main sources of information
      regarding medicines. In terms of beliefs, respondents showed wrong beliefs in
      many statements used in this study. CONCLUSION: There is a need to improve public
      knowledge and beliefs toward medicines as well as utilizing public preferred
      dosage forms. In addition, pharmacists should play a major role in these programs
      since they are experts on medicines and play a more active role in patient
      education and counseling.

PMID- 24888658
TI  - Smoking habits and cessation success. What differs among adults and elderly?
AB  - OBJECTIVE: To determine factors affecting smoking cessation success in different
      age groups. METHODS: This was an intervention study consisting of 761 patients
      attending the Balcova Municipality, Smoke Cessation Center, Izmir, Turkey,
      between November 2009 and December 2011. Variables were successful smoking
      cessation for one year, socio-demographic features, previous attempts at smoking
      cessation, a smoking spouse, nicotine dependency level, risk of depression,
      method of smoking cessation, presence of chronic disease, and decreasing smoking
      in the last year. Data was analyzed by logistic regression. RESULTS:
      Approximately 43.8% of the elderly, and 62.7% of the adults reduced the number of
      cigarettes smoked in the past year. Approximately 83.6% of the elderly and 90.6%
      of the adults reported previously smoking 11 or more cigarettes daily. Two-thirds
      of the participants in both groups had tried smoking cessation. Smoking cessation
      was 49% in the elderly group and 33.4% in the adult group. The logistic
      regression test showed that moderate and less nicotine dependency level increased
      the success of cessation in the elderly group (odds ratio [OR]=2.39, 95%
      confidence interval [95% CI] 1.11-5.17, p=0.026), while in the adult group:
      increasing age (OR=1.02, 95% CI: 1.01-1.04, p=0.044), male gender (OR=1.69, 95%
      CI: 1.07-2.68, p=0.025), moderate and less nicotine dependency level (OR=1.65,
      95% CI: 1.09-2.49, p=0.018), and the use of medication (OR=1.70, 95% CI: 1.13
      2.56, p=0.011) increased the success. CONCLUSION: Different variables in
      different age groups may affect successful smoking cessation. These should be
      taken into consideration in efforts at smoking cessation.

PMID- 24888659
TI  - Early prevention of childhood caries with maternal xylitol consumption.
AB  - OBJECTIVE: To evaluate the effect of maternal xylitol consumption on children's
      salivary mutans streptococci (MS) level, caries activity, and plaque accumulation
      in contrast with maternal fluoride varnish in a group of mother-child pairs.
      METHODS: In this randomized controlled trial, the study subjects were 60 mother
      child pairs recruited from the pediatric dentistry clinic and the hospital well
      baby clinic at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. The
      sample was recruited on the basis of maternal high salivary MS levels, and a
      child aged 10-36 months. The subjects were randomly assigned to experimental and
      control groups. Mothers in the experimental group chewed xylitol gum, 1.8 gram
      (66% xylitol by weight), 3 times/day for 3 months. Mothers in the control group
      received fluoride varnish. Both groups received oral hygiene instructions,
      dietary counseling, and restorative treatment. Children were examined after 6,
      12, and 24 months from the initiation of the study to evaluate salivary MS
      levels, caries, and plaque accumulation. RESULTS: There was an increase in MS
      levels in the experimental and control children at 24 months, which was non
      significant in the experimental group, and significantly higher in the control
      group when compared with the baseline (p=0.008). The decayed, missing, filled
      scores of the children in the experimental group showed no change after 24
      months, contrary to the controls that showed a significant increase (p=0.001).
      Plaque scores revealed no differences over time or between the 2 groups.
      CONCLUSION: Compared with fluoride varnish, maternal xylitol consumption provided
      preventive outcomes on salivary MS and caries levels in children.

PMID- 24888660
TI  - The prevalence, causes, and relativity of dental anxiety in adult patients to
      irregular dental visits.
AB  - OBJECTIVE: To assess the frequency and causes of dental anxiety and their
      relation to irregular dental visits among adult dental patients. METHODS: The
      Dental Anxiety Question (DAQ) included within a self-administered questionnaire
      was distributed to 1025 patients attending the Interns' Dental Clinics in the
      Department of Preventive Dental Sciences, College of Dentistry, University of
      Dammam, Dammam, Kingdom of Saudi Arabia from March 2012 to February 2013. A cross
      sectional study design was used. The questionnaire consisted of 22 closed-ended
      questions divided into 4 sections; 1) demographics, 2) regularity of dental
      visits, and related causes, 3) DAQ, cancellation of dental appointments, history
      of previous trauma, dental anxiety provoking factors within dental environment
      and procedures, and 4) patients' status in dental clinics, preferences of
      dentists, and perceptions regarding dental anxiety. RESULTS: The prevalence of
      dental anxiety among the study sample was 27%. Anesthetic injection was the main
      factor of dental fear (88.2%), while dental surgical procedures (35.7%) and
      extractions (23%) were the most terrifying dental procedures. Lack of time
      (79.5%), cost (71.5%), far-situated dental services (62.2%), and fear (57.1%)
      were causes listed for irregular dental visits; while 31.3% had no specific
      reason. Irregular dental visits were not related to dental anxiety. CONCLUSION:
      Dental anxiety continues to be an obstacle despite the vast improvement in
      dentistry; and this raises an alert regarding personal and communication factors
      in the patient-dentist relationship. Factors such as equal distribution of dental
      services, time, and cost should also be addressed.

PMID- 24888661
TI  - Hemobilia due to liver abscess. A rare cause of massive upper gastrointestinal
      bleeding.
AB  - Massive hemobilia is a rare complication of liver abscess. A 48-year-old male
      presented with massive hemobilia due to liver abscess. He had been complaining of
      right upper quadrant abdominal pain, fever, and jaundice for 10 days. This was
      followed by hematemesis and melena prior to emergency presentation. Upper
      gastrointestinal endoscopy showed fresh blood and clots coming from the orifice
      of the ampulla of Vater. The CT showed multiple liver abscesses, the largest one
      in the right lobe. Selective angiography revealed bleeding from a branch of the
      right hepatic artery into the biliary radicles. The bleeding was controlled by
      coil embolization. Drainage of the large liver abscesses was achieved under
      ultrasound guidance. Diagnostic modalities and management of hemobilia are
      discussed along with a review of the literature. A high index of suspicion, and
      the use of appropriate diagnostic tools can help diagnose and treat this rare
      cause of upper gastrointestinal bleeding. 

PMID- 24888662
TI  - Solitary neurofibroma of the gingiva.
AB  - Neurofibroma is a benign peripheral nerve sheath tumor, usually found in
      association with Von Recklinghausen's disease of the skin. The solitary variant
      commonly occurs in the head and neck region, mostly affecting young adults. They
      are characteristically slow-growing masses, often asymptomatic and have been
      found most commonly in the tongue and buccal mucosa. A recent literature review
      highlighting incidences in various other locations has been tabulated here. We
      also report a case of a solitary neurofibroma of the gingiva in a 72-year-old
      male of 15 years duration. Histopathology revealed a fibromyxoid stroma with
      sinuous nerve bundles with buckled nuclei. 

PMID- 24888663
TI  - Chemotherapy-induced febrile neutropenia in patients with breast cancer. A
      multivariate risk assessment model for first cycle chemotherapy.
AB  - OBJECTIVE: To identify factors that increase the risk of developing febrile
      neutropenia (FN) during the first cycle of chemotherapy in breast cancer
      patients. METHODS: In this retrospective study, we reviewed the records of 211
      patients with confirmed breast cancer treated with chemotherapy at the Princess
      Norah Oncology Center, King Abdulaziz Medical City, Jeddah, Kingdom of Saudi
      Arabia between January 2010 and May 2012. Statistical analysis was conducted
      using descriptive analysis, univariate, and multivariate logistic regressions. A
      multivariate regression of FN occurrence in the first cycle was developed.
      RESULTS: The median age of patients was 48 years. Febrile neutropenia was
      documented in 43 (20.3%) of 211 patients. Twenty-one (49%) of the 43 patients had
      FN during the first cycle of chemotherapy. A multivariate logistic regression
      revealed that age (odds ratio [OR] 1.059, 95% confidence interval [CI]: 1.007
      1.114), non-anthracycline and/or taxane-based chemotherapy regimens (OR of
      39.488; 95% CI: 4.995-312.187), and neo-adjuvant chemotherapy (OR of 8.282; 95%
      CI: 1.667-41.152) were the most important independent risk factors of FN.
      CONCLUSION: Identifying risk factors of FN may help to target high-risk patients
      with granulocyte colony-stimulating factor prophylaxis and reduce FN incidences,
      with subsequent morbidities and mortalities.

PMID- 24888664
TI  - Selenium levels in rice samples from high and low risk areas for esophageal
      cancer.
AB  - OBJECTIVE: To assess the relationship between selenium (Se) concentration in rice
      and the incidence of esophageal cancer (EC) in a high risk area in Northern Iran.
      METHODS: This ecological study was conducted in Golestan province of Iran in
      2012. In this area, 45714 acres of land are cultivated by rice. A total of 69
      rice samples were taken. We investigated Se concentrations by the voltammetric
      method. Statistical analysis was performed using the Pearson correlation test and
      Mann-Whitney U test. RESULTS: The mean (+/-SD) Se level in rice samples was 0.229
      (+/-0.145) mg/kg. The Se concentration was significantly higher in rice samples
      from high EC rate areas (0.35 mg/kg) compared with low risk areas (0.16 mg/kg)
      (p<0.001). There was a significant positive correlation between the levels of Se
      in rice and the incidence rate of EC (p=0.03). CONCLUSION: We found a high rice
      Se concentration and a significant positive relationship between rice Se levels
      and EC rates in the Golestan province of Iran. High soil and rice Se levels may
      play a possible role in the pathogenesis of EC in this area.

PMID- 24888665
TI  - Bariatric surgery. Its role in 'curing' diabetes.

PMID- 24888666
TI  - Clinical and laboratory characteristics of childhood pandemic 2009 H1N1
      Influenza. Experience from the western region of Saudi Arabia.

PMID- 24888667
TI  - Abscess of the axilla in hypertensive adult female.

PMID- 24888668
TI  - Label-free quantitative proteomic analysis of human plasma-derived microvesicles
      to find protein signatures of abdominal aortic aneurysms.
AB  - PURPOSE: To find potential biomarkers of abdominal aortic aneurysms (AAA), we
      performed a differential proteomic study based on human plasma-derived
      microvesicles. EXPERIMENTAL DESIGN: Exosomes and microparticles isolated from
      plasma of AAA patients and control subjects (n = 10 each group) were analyzed by
      a label-free quantitative MS-based strategy. Homemade and publicly available
      software packages have been used for MS data analysis. RESULTS: The application
      of two kinds of bioinformatic tools allowed us to find differential protein
      profiles from AAA patients. Some of these proteins found by the two analysis
      methods belong to main pathological mechanisms of AAA such as oxidative stress,
      immune-inflammation, and thrombosis. CONCLUSIONS AND CLINICAL RELEVANCE: Data
      analysis from label-free MS-based experiments requires the use of sophisticated
      bioinformatic approaches to perform quantitative studies from complex protein
      mixtures. The application of two of these bioinformatic tools provided us a
      preliminary list of differential proteins found in plasma-derived microvesicles
      not previously associated to AAA, which could help us to understand the
      pathological mechanisms related to this disease.

PMID- 24888670
TI  - Clinical normative data for eating disorder examination questionnaire and eating
      disorder inventory for DSM-5 feeding and eating disorder classifications: a
      retrospective study of patients formerly diagnosed via DSM-IV.
AB  - Normative data for measures of eating disorder (ED) psychopathology provide a
      fundamental description of a presentation and a means to establish clinically
      significant change following an intervention. Clinical norms for the ED
      population are lacking and out of date following the publication of Diagnostic
      and Statistical Manual of Mental Health Disorders (DSM) 5. This study aimed to
      show that scores from the Eating Disorder Examination Questionnaire (EDE-q) and
      the Eating Disorder Inventory (EDI) differ across ED diagnosis groups and provide
      norm data for DSM-5 ED diagnoses. Patients (n = 932) presenting to an out-patient
      service over 5 years were retrospectively re-diagnosed based on DSM-5 criteria.
      Statistical analysis showed a significant difference on most subscale scores of
      the EDE-q and the EDI across diagnosis. Means, standard deviations and percentile
      ranks are presented by diagnosis. The norms detailed contribute to improving the
      accuracy with which scores are interpreted when using DSM-5 and aid with the
      assessment of clinically significant change following treatment.

PMID- 24888669
TI  - Chasing helminths and their economic impact on farmed ruminants.
AB  - Global agriculture will be required to intensify production from a shrinking
      natural resource base. Helminth infections of ruminants are a major constraint on
      efficient livestock production. The current challenge is to develop diagnostic
      methods that detect the production impact of helminth infections on farms in
      order to target control measures and contribute to the global challenge of
      preserving food security. We review here our understanding of the effects of
      helminth infections and control practices on productivity and the diagnostic
      tools that can inform on this. By combining advances in helminth laboratory
      diagnostics and animal health economics, sustainable management of helminth
      infections can be integrated into the whole-farm economic context. 

PMID- 24888671
TI  - Living on the edge of asthma: A grounded theory exploration.
AB  - PURPOSE: Most asthma-related emergency department (ED) visits and
      hospitalizations for asthma are preventable. Our purpose was to develop a
      grounded theory to guide interventions to reduce unnecessary hospitalizations and
      ED visits. DESIGN AND METHODS: Grounded theory inquiry guided interviews of 20
      participants, including 13 parents and 7 children. RESULTS: Living on the edge of
      asthma was the emergent theory. Categories included: balancing, losing control,
      seeking control, and transforming. PRACTICE IMPLICATIONS: The theory provides the
      means for nurses to understand the dynamic process that families undergo in
      trying to prevent and then deal with and learn from an acute asthma attack
      requiring hospitalization or an ED visit.

PMID- 24888672
TI  - Temperament and character in remitted and symptomatic patients with
      schizophrenia: modulation by the COMT Val158Met genotype.
AB  - While research on remission in schizophrenia has gained attention, personality
      characteristics associated with remission in schizophrenia have been under
      studied. A functional valine-to-methionine (Val158Met) polymorphism in the
      catechol-O-methyltransferase (COMT) gene is shown to modify clinical presentation
      of schizophrenia despite weak or no association with the disorder itself. Studies
      also report that this polymorphism can affect personality traits. We aimed to
      examine personality traits of remitted patients with schizophrenia as compared to
      symptomatic patients and healthy controls and to investigate whether the COMT
      Val158Met polymorphism influences their personality. Scores on the Temperament
      and Character Inventory were compared between 34 remitted outpatients with
      schizophrenia, age- and sex-matched 72 symptomatic outpatients with
      schizophrenia, and matched 247 healthy individuals. The effect of COMT Val158Met
      polymorphism on personality was examined in each group. The analysis of
      covariance, controlling for confounding variables, revealed that compared to
      healthy controls, symptomatic patients exhibited a pervasively altered
      personality profile whereas remitted patients showed alterations in more limited
      personality dimensions and demonstrated normal levels of novelty-seeking, reward
      dependence and cooperativeness. The two-way analysis of covariance, with genotype
      and sex as between-subject factors and confounders as covariates, revealed that
      Met carriers demonstrated significantly lower reward dependence and
      cooperativeness than Val homozygotes in symptomatic patients; while no
      significant genotype effect was found in remitted patients or in healthy
      individuals. These findings indicate that remitted patients with schizophrenia
      have a relatively adaptive personality profile compared to symptomatic patients.
      The COMT Val158Met polymorphism might have a modulating effect on the
      relationship between personality and remission. 

PMID- 24888673
TI  - Variation in charges for emergency department visits across California.
AB  - STUDY OBJECTIVE: Previous studies have shown that charges for inpatient and
      clinic procedures vary substantially; however, there are scant data on variation
      in charges for emergency department (ED) visits. Outpatient ED visits are
      typically billed with current procedural terminology-coded levels to standardize
      the intensity of services received, providing an ideal element on which to
      evaluate charge variation. Thus, we seek to analyze the variation in charges for
      each level of ED visits and examine whether hospital- and market-level factors
      could help predict these charges. METHODS: Using 2011 charge data provided by
      every nonfederal California hospital to the Office of Statewide Health Planning
      and Development, we analyzed the variability in charges for each level of ED
      visits and used linear regression to assess whether hospital and market
      characteristics could explain the variation in charges. RESULTS: Charges for each
      ED visit level varied widely; for example, charges for a level 4 visit ranged
      from $275 to $6,662. Government hospitals charged significantly less than
      nonprofit hospitals, whereas hospitals that paid higher wages, served higher
      proportions of Medicare and Medicaid patients, and were located in areas with
      high costs of living charged more. Overall, our models explained only 30% to 41%
      of the between-hospital variation in charges for each level of ED visits.
      CONCLUSION: Our findings of extensive charge variation in ED visits add to the
      literature in demonstrating the lack of systematic charge setting in the US
      health care system. These widely varying charges affect the hospital bills of
      millions of uninsured patients and insured patients seeking care out of network
      and continue to play a role in many aspects of health care financing.

PMID- 24888674
TI  - Activation of carboxylic acids in asymmetric organocatalysis.
AB  - Organocatalysis, catalysis using small organic molecules, has recently evolved
      into a general approach for asymmetric synthesis, complementing both metal
      catalysis and biocatalysis. Its success relies to a large extent upon the
      introduction of novel and generic activation modes. Remarkably though, while
      carboxylic acids have been used as catalyst directing groups in supramolecular
      transition-metal catalysis, a general and well-defined activation mode for this
      useful and abundant substance class is still lacking. Herein we propose the
      heterodimeric association of carboxylic acids with chiral phosphoric acid
      catalysts as a new activation principle for organocatalysis. This self-assembly
      increases both the acidity of the phosphoric acid catalyst and the reactivity of
      the carboxylic acid. To illustrate this principle, we apply our concept in a
      general and highly enantioselective catalytic aziridine-opening reaction with
      carboxylic acids as nucleophiles.

PMID- 24888676
TI  - Open wide: blindness in cats after the use of mouth gags.

PMID- 24888675
TI  - Cervical spondylomyelopathy in Great Danes: a magnetic resonance imaging
      morphometric study.
AB  - Morphometric investigations comparing normal and affected animals increase our
      understanding of spinal diseases in dogs. The aim of this study was to generate
      morphometric data for osseous-associated cervical spondylomyelopathy (CSM) in
      Great Danes (GDs). Magnetic resonance imaging (MRI) morphometric features of the
      cervical vertebral column of GDs with and without clinical signs of CSM were
      characterized and compared. Thirty client-owned GDs were prospectively enrolled,
      including 15 clinically normal and 15 CSM-affected GDs. All dogs underwent MRI of
      the cervical to thoracic vertebral column (C2-C3 through T1-T2). Areas of the
      cranial and caudal articular processes, and the height, width and areas of the
      vertebral canal and spinal cord were determined. Middle foraminal heights were
      measured. Intervertebral disc width was measured before and after traction.
      Intraobserver and interobserver agreement were calculated. CSM-affected GDs had
      larger areas of the caudal articular processes from C2-C3 through T1-T2. In CSM
      affected GDs, the vertebral canal and spinal cord areas were significantly
      smaller at C5-C6 and C6-C7, the vertebral canal width was significantly narrower
      at C6-C7 and C7-T1, and the spinal cord width was significantly narrower at C5-C6
      and C6-C7. Middle foraminal height was smaller in CSM-affected GDs from C3-C4
      through C7-T1. Neutral intervertebral disc widths were smaller in CSM-affected
      GDs. It was concluded that the cervical vertebral canal dimensions are
      significantly different between normal and CSM-affected GDs. Absolute vertebral
      canal stenosis and severe foraminal stenosis involving the cervical vertebrae
      distinguish CSM-affected from clinically normal GDs. These findings are relevant
      to the pathogenesis of osseous-associated CSM and should be taken into
      consideration when performing imaging studies and planning surgery.

PMID- 24888677
TI  - Exercise influences circadian gene expression in equine skeletal muscle.
AB  - Circadian rhythms are endogenously generated 24-h oscillations that coordinate
      numerous aspects of mammalian physiology, metabolism and behaviour. The existence
      of a molecular circadian clock in equine skeletal muscle has previously been
      demonstrated. This study investigates how the circadian 24-h expression of
      exercise-relevant genes in skeletal muscle is influenced by a regular exercise
      regime. Mid-gluteal, percutaneous muscle biopsies were obtained over a 24-h
      period from six Thoroughbred mares before and after an 8-week exercise programme.
      Real-time qPCR assays were used to assess the expression patterns of core clock
      genes ARNTL, PER2, NR1D1, clock-controlled gene DBP, and muscle genes MYF6, UCP3,
      VEGFA, FOXO1, MYOD1, PPARGC1A, PPARGC1B, FBXO32 and PDK4. Two-way repeated
      measures ANOVA revealed a significant interaction between circadian time and
      exercise for muscle genes MYF6, UCP3, MYOD1 and PDK4. A significant effect of
      time was observed for all genes with the exception of VEGFA, where a main effect
      of exercise was observed. By cosinor analysis, the core clock genes, ARNTL (P
      <0.01) and NR1D1 (P <0.05), showed 24-h rhythmicity both pre- and post-exercise,
      while PER2 expression was rhythmic post-exercise (P <0.05) but not pre-exercise.
      The expression profiles of muscle genes MYOD1 and MYF6 showed significant fits to
      a 24-h cosine waveform indicative of circadian rhythmicity post-exercise only (P
      <0.01). This study suggests that the metabolic capacity of muscle is influenced
      by scheduled exercise and that optimal athletic performance may be achieved when
      exercise times and competition times coincide.

PMID- 24888678
TI  - Magnetic resonance imaging signs of presumed elevated intracranial pressure in
      dogs.
AB  - The aim of this study was to describe magnetic resonance imaging (MRI) findings
      associated with presumed elevated intracranial pressure (ICP) in dogs and to
      evaluate whether MRI could be used to discriminate between dogs with and without
      elevated ICP. Of 91 dogs that underwent cranial MRI examination, 18 (19.8%) were
      diagnosed with elevated ICP based on neurological examination, fundoscopy and
      transcranial Doppler ultrasonography. The MRI findings that showed the strongest
      association with elevated ICP were mass effect (odds ratio [OR], 78.5), caudal
      transtentorial herniation (OR, 72.0), subfalcine herniation (OR, 45.6),
      perilesional oedema (OR, 34.0), displacement of the lamina quadrigemina (OR,
      27.7) and effacement of the cerebral sulci (OR, 27.1). The presence of any two or
      more of the following MRI findings identified elevated ICP with a sensitivity of
      72% and a specificity of 96%: compression of the suprapineal recess, compression
      of the third ventricle, compression of the fourth ventricle, effacement of the
      cerebral sulci and caudal transposition of the lamina quadrigemina. In
      conclusion, there is an association between MRI findings and elevated ICP in
      dogs; therefore, MRI might be useful to discriminate between dogs with and
      without elevated ICP. 

PMID- 24888679
TI  - Evaluation of impulse oscillometry in pigs of unknown disease status originating
      from the field.
AB  - The aim of this study was to assess impulse oscillometry as a method to
      characterise lung function in 58 German hybrid pigs from 29 different herds of
      unknown respiratory status. The variability of repeated lung function
      measurements increased significantly after the sixth run and therefore the
      average of the first six runs was used for analysis. The presence of peripheral
      respiratory alterations in some pigs was indicated by the negative frequency
      dependence of the 95th percentile of respiratory resistance (Rrs), with highest
      values at 3 Hz and the sharp drop of respiratory reactance (Xrs) across the whole
      frequency range (3-15 Hz). Respiratory resistance and reactance were negatively
      correlated. Reactance area was correlated with (1) Rrs at 3, 5 and 10 Hz; (2) Xrs
      at 3, 5, 10 and 15 Hz; (3) the frequency dependence of resistance compared
      between 3 and 5 Hz (R3-R5), 5 and 10 Hz (R5-R10), and 5 and 15 Hz (R5-R15); and
      (4) tidal volume. High repeatability and low intra-individual variability of
      impulse oscillometry indicate that this method is a promising tool for advanced
      characterisation of the pulmonary system of pigs and has potential for use for
      herd health monitoring.

PMID- 24888680
TI  - Drug-drug interactions: an evolving science in need of experimental models and
      systems.

PMID- 24888682
TI  - Idiopathic headshaking: is it still idiopathic?

PMID- 24888681
TI  - In vivo effects of phenylbutazone on inflammation and cartilage-derived
      biomarkers in equine joints with acute synovitis.
AB  - Although phenylbutazone (PBZ) is commonly used in equine orthopaedic practice,
      little is known about its in vivo effects on joint inflammation and cartilage
      turnover. This study investigates the effects of PBZ on inflammatory parameters,
      matrix metalloproteinase (MMP) activity and cartilage biomarkers in equine joints
      with acute synovitis. In a two-period cross-over study, transient synovitis was
      induced at T = 0 h in the middle carpal joint of seven ponies by
      lipopolysaccharide (LPS) injection. Ponies received PBZ (2 mg/kg PO twice daily)
      or placebo for 1 week, starting at T = 2 h. Arthroscopic assessment of the middle
      carpal joint was performed at T = -504, 48 and 672 h. Synovial fluid (SF) was
      sampled at T = -504, 0, 8, 24, 48, 168, 336 and 672 h and analysed for leukocytes
      and total protein, substance P, general MMP activity, glycosaminoglycans (GAG),
      collagen II cleavage marker C2C and synthesis marker CPII. Markers in PBZ- vs.
      placebo-treated joints were compared over time using a linear mixed model. LPS
      injection caused marked transient synovitis without visible cartilage changes.
      Substance P and general MMP activity were not significantly reduced by PBZ
      treatment, nor were SF GAG or C2C concentrations at any time point. Concentration
      of CPII was significantly lower at T = 24 and 168 h in PBZ treated joints
      compared to placebo. Although PBZ is clinically effective in treating acute
      synovitis, it does not limit inflammation-induced cartilage catabolism and may
      transiently reduce collagen anabolism as evidenced by SF markers.

PMID- 24888683
TI  - Production of a mitochondrial-DNA identical cloned foal using oocytes recovered
      from immature follicles of selected mares.
AB  - Cloned animals possess mitochondria derived from the host ooplast, which
      typically differ genetically from those of the donor. This is of special concern
      to horse breeders, as maternal lines are prized and athletic performance is a key
      factor in genetic value. To evaluate the feasibility of producing mitochondrial
      identical cloned foals, we collected oocytes from immature follicles of two
      mares, BL and SM, maternally related to the donor stallion. In vitro matured,
      enucleated oocytes were treated with roscovitine-synchronized donor cells and
      blastocysts were transferred transcervically to recipient mares. In Mare BL, 10
      aspiration sessions yielded 45 oocytes, of which 12 matured and seven were
      successfully recombined. One blastocyst was produced, which did not yield a
      pregnancy. In Mare SM, three aspiration sessions yielded 53 oocytes, of which 27
      successfully recombined. These were assigned to either Scriptaid or Scriptaid
      plus Vitamin C treatments for the first 12 to 16 hours of embryo culture. Two
      blastocysts were produced from each treatment. One pregnancy was established
      after transfer from the Scriptaid treatment. This resulted in a viable foal whose
      genomic DNA and mitochondrial DNA matched to those of the donor animal. These
      results indicate that production of mitochondrial-identical cloned foals can be
      achieved using oocyte recovery from a very small number of selected mares.
      Despite mitochondrial homogeneity, the results varied with mare; Mare BL yielded
      both significantly fewer oocytes per aspiration session (P < 0.001) and
      significantly fewer reconstructed oocytes per oocyte recovered ( P < 0.001) than
      did Mare SM.

PMID- 24888684
TI  - Canine fetal heart rate: do accelerations or decelerations predict the
      parturition day in bitches?
AB  - Ultrasonography is a safe and efficient technique for monitoring fetal
      development and viability. One of the most important and widely used parameters
      to verify fetal viability is the fetal heart rate (HR). In human medicine, the
      fetal HR normally oscillates during labor in transient accelerations and
      decelerations associated with uterine contractions. The present study
      investigated whether these variations also occur in canine fetuses and its
      relationship to parturition. A cohort study was conducted in 15 pregnant bitches
      undergoing two-dimensional high-resolution ultrasonographic examination during
      the 8th and 9th week of gestation. Fetal HR was assessed in M-mode for 5 minutes
      in each fetus in all bitches. In addition, the bitches were monitored for
      clinical signs of imminent parturition. Associations between the HR, antepartum
      time, and delivery characteristics were evaluated with a Poisson regression
      model. Fetal HR acceleration and deceleration occurred in canine fetuses and
      predicted the optimal time of parturition. These findings can help veterinarians
      and sonographers better understand this phenomenon in canine fetuses. 

PMID- 24888685
TI  - Exposure of prepubertal beef bulls to cycling females does not enhance sexual
      development.
AB  - The objective of this study was to determine whether continuous, long-term,
      fenceline exposure of prepubertal beef bulls to cycling beef females reduced age
      at puberty and influenced the percentage of bulls that passed an initial breeding
      soundness examination (BSE). Bulls (Angus, n = 37; Simmental, n = 22; Hereford, n
      = 10; Simmental * Angus, n = 8) at an average age of 202 +/- 21.5 days were given
      either continuous fenceline and visual exposure to cycling females (exposed, n =
      41) or no exposure (control, n = 36). Estrus was induced in cycling beef females
      so at least three females were in standing estrus each week during the 182 days
      of exposure to bulls. Scrotal circumference (SC), body weight, and blood samples
      were collected every 28 days. When bulls had SC of 26 cm or more, semen samples
      were obtained monthly via electroejaculation until puberty was achieved (>=50 *
      10(6) sperm/mL with at least 10% progressive motility). Behavioral observations
      were conducted twice monthly: once when females were in estrus and once during
      diestrus. Homosexual mounting, flehmen responses, and number of times near penned
      females were recorded for each observation period. Breeding soundness
      examinations were conducted when the average age of bulls was 364 +/- 21.5 days.
      Normal sperm morphology of at least 70% and sperm motility of at least 30% were
      required to pass the BSE. Age, body weight, and SC at puberty did not differ
      between exposed and control bulls (320 +/- 28 and 311 +/- 29 days; 466.2 +/- 12.2
      and 437.7 +/- 13.5 kg; and 34.4 +/- 2.5 and 34.9 +/- 2.5 cm, respectively).
      Percentage of bulls passing their initial BSE did not differ between treatments
      (exposed, 87.8%; control, 75.0%). Treatment, month, and female estrous stage
      interacted (P = 0.05) to affect the number of mount attempts and flehmen
      responses. Exposed bulls entered the cow area more times (P < 0.001) during
      estrus than diestrus in Months 1, 2, and 3. We concluded that bulls given
      continuous, long-term, fenceline exposure to cycling beef females do not have
      enhanced sexual development.

PMID- 24888686
TI  - Effects of altering the dose and timing of triptorelin when given as an
      intravaginal gel for advancing and synchronizing ovulation in weaned sows.
AB  - Previous studies have shown that triptorelin gel (TG) given intravaginally in gel
      form is effective for advancing the time of ovulation in weaned sows. Three
      experiments were performed to determine the effects of altering the dose and
      timing of administration of intravaginal TG for advancing and synchronizing
      ovulation in weaned sows. In all experiments, estrus was detected twice or three
      times daily and ultrasound was performed to determine ovulation at 8-hour
      intervals. In experiment 1, sows (n = 131) received intravaginal gel containing 0
      (Placebo), 25, 100, or 200 MUg of TG at 96 hours after weaning and sows were
      inseminated on each day of standing estrus. Wean-to-estrus interval and duration
      of estrus were correlated (P < 0.0001) with estrus duration longer in TG (P <
      0.05) compared with Placebo. More sows ovulated (P < 0.001) by 48 hours after
      treatment with 200 (81%), 100 (64%), and 25 MUg (63%) of TG compared with Placebo
      (42%). The farrowing rate and total pigs born did not differ (P > 0.10). In
      experiment 2, sows (n = 126) received 200 MUg of TG at 72, 84, or 96 hours after
      weaning or were untreated (Control-96). Sows receiving TG were inseminated once
      24 to 28 hours after treatment. Control-96 sows were inseminated on each day of
      standing estrus. Wean-to-estrus interval was not affected by treatment, but wean
      to-ovulation interval was reduced (P < 0.05) by TG-72 and TG-84 compared with TG
      96 and Control-96. More sows ovulated 40 hours after treatment (P < 0.001) with
      TG-72 (56.5%) and TG-84 (32.2%) compared with TG-96 and Control-96 (13%) and for
      all TG treatments 48 hours after treatment (64%) compared with Control-96 (34%, P
      < 0.05). The farrowing rate was lower (P < 0.05) for sows assigned to TG-72 and
      TG-84 compared with TG-96 and Control-96, whereas the number of liveborn pigs did
      not differ (P > 0.10). In experiment 3, sows (n = 113) were assigned to receive
      no treatment (Control), intravaginal gel alone (Placebo), or 200 MUg of TG given
      intravaginally (OvuGel) at 96 hours after weaning. Wean-to-estrus interval did
      not differ, but the duration of estrus tended (P < 0.10) to be reduced with
      OvuGel compared with the other treatments. More sows ovulated (P < 0.001) by 48
      hours after OvuGel treatment (79.1%) compared with Control (46.4%) and Placebo
      (37.9%) and by 56 hours (P < 0.05). The farrowing rate and the number of liveborn
      pigs did not differ among treatments. The results of these studies indicate that
      200 MUg of TG given intravaginally at 96 hours after weaning (OvuGel)
      synchronizes ovulation and results in fertility similar to Controls.

PMID- 24888688
TI  - Soft grippers using micro-fibrillar adhesives for transfer printing.
AB  - The adhesive characteristics of fibrillar adhesives on a soft deformable membrane
      are reported. A soft gripper with an inflatable membrane covered by elastomer
      mushroom-shaped microfibers have a superior conformation to non-planar 3D part
      geometries, enabling the transfer printing of various parts serially or in
      parallel. 

PMID- 24888689
TI  - Heroin and cannabis use is declining but new drugs show increase, says EU report.

PMID- 24888687
TI  - Osteopontin facilitates ultraviolet B-induced squamous cell carcinoma
      development.
AB  - BACKGROUND: Osteopontin (OPN) is a matricellular glycoprotein that is markedly
      expressed in cutaneous squamous cell carcinomas (cSCCs) and in actinic keratoses
      implicating its role in photocarcinogenesis. OBJECTIVE: To determine whether OPN
      facilitates the development of cSCC and its function. METHODS: cSCCs development
      was compared between wild-type (WT) and OPN-null mice subjected to UVB
      irradiation for 43 weeks. UVB-induced OPN expression was determined by Western
      blot, immunoprecipitation, ELISA, and semi-quantitative RT-PCR. Epidermal layer
      and TUNEL analyses assessed if OPN mediates UVB-induced epidermal hyperplasia or
      suppresses UVB-induced apoptosis of basal keratinocytes, respectively. In vitro
      experiments determined whether OPN enhances cell survival of UVB-induced
      apoptosis and its potential mechanisms. Immunohistochemical analyses of epidermis
      assessed the expression of CD44 and focal adhesion kinase (FAK), molecules that
      mediate OPN survival function. RESULTS: Compared to female WT mice, OPN-null mice
      did not develop cSCCs. UVB irradiation stimulated OPN protein expression in the
      dorsal skin by 11h and remains high at 24-48h. OPN did not mediate UVB-induced
      epidermal hyperplasia; instead, it protected basal keratinocytes from undergoing
      apoptosis upon UVB exposure. Likewise, the addition of OPN suppressed UVB-induced
      OPN-null cSCC cell apoptosis, the activation of caspase-9 activity, and increased
      phosphorylation of FAK at Y397. Furthermore, the expression of CD44 and FAK in WT
      mice epidermis was greater than that of OPN-null mice prior to and during early
      acute UVB exposure. CONCLUSION: These data support the hypothesis that chronic
      UVB-induced OPN expression protects the survival of initiated basal keratinocytes
      and, consequently, facilitates cSCC develop.

PMID- 24888690
TI  - The force-from-lipid (FFL) principle of mechanosensitivity, at large and in
      elements.
AB  - Focus on touch and hearing distracts attention from numerous subconscious force
      sensors, such as the vital control of blood pressure and systemic osmolarity, and
      sensors in nonanimals. Multifarious manifestations should not obscure invariant
      and fundamental physicochemical principles. We advocate that force from lipid
      (FFL) is one such principle. It is based on the fact that the self-assembled
      bilayer necessitates inherent forces that are large and anisotropic, even at
      life's origin. Functional response of membrane proteins is governed by bilayer
      force changes. Added stress can redirect these forces, leading to geometric
      changes of embedded proteins such as ion channels. The FFL principle was first
      demonstrated when purified bacterial mechanosensitive channel of large
      conductance (MscL) remained mechanosensitive (MS) after reconstituting into
      bilayers. This key experiment has recently been unequivocally replicated with two
      vertebrate MS K2p channels. Even the canonical Kv and the Drosophila canonical
      transient receptor potentials (TRPCs) have now been shown to be MS in biophysical
      and in physiological contexts, supporting the universality of the FFL paradigm.
      We also review the deterministic role of mechanical force during stem cell
      differentiation as well as the cell-cell and cell-matrix tethers that provide
      force communications. In both the ear hair cell and the worm's touch neuron,
      deleting the cadherin or microtubule tethers reduces but does not eliminate MS
      channel activities. We found no evidence to distinguish whether these tethers
      directly pull on the channel protein or a surrounding lipid platform. Regardless
      of the implementation, pulling tether tenses up the bilayer. Membrane tenting is
      directly visible at the apexes of the stereocilia. 

PMID- 24888691
TI  - Mechanotransduction in the muscle spindle.
AB  - The focus of this review is on the principal sensory ending of the mammalian
      muscle spindle, known as the primary ending. The process of mechanosensory
      transduction in the primary ending is examined under five headings: (i) action
      potential responses to defined mechanical stimuli-representing the ending's input
      output properties; (ii) the receptor potential-including the currents giving rise
      to it; (iii) sensory-terminal deformation-measurable changes in the shape of the
      primary-ending terminals correlated with intrafusal sarcomere length, and what
      may cause them; (iv) putative stretch-sensitive channels-pharmacological and
      immunocytochemical clues to their identity; and (v) synaptic-like vesicles-the
      physiology and pharmacology of an intrinsic glutamatergic system in the primary
      and other mechanosensory endings, with some thoughts on the possible role of the
      system. Thus, the review highlights spindle stretch-evoked output is the product
      of multi-ionic receptor currents plus complex and sophisticated regulatory gain
      controls, both positive and negative in nature, as befits its status as the most
      complex sensory organ after the special senses. 

PMID- 24888692
TI  - Reduced tissue-level stiffness and mineralization in osteoporotic cancellous
      bone.
AB  - Osteoporosis alters bone mass and composition ultimately increasing the fragility
      of primarily cancellous skeletal sites; however, effects of osteoporosis on
      tissue-level mechanical properties of cancellous bone are unknown. Dual-energy X
      ray absorptiometry (DXA) scans are the clinical standard for diagnosing
      osteoporosis though changes in cancellous bone mass and mineralization are
      difficult to separate using this method. The goal of this study was to
      investigate possible difference in tissue-level properties with osteoporosis as
      defined by donor T scores. Spine segments from Caucasian female cadavers (58-92
      years) were used. A T score for each donor was calculated from DXA scans to
      determine osteoporotic status. Tissue-level composition and mechanical properties
      of vertebrae adjacent to the scan region were measured using nanoindentation and
      Raman spectroscopy. Based on T scores, six samples were in the Osteoporotic group
      (58-74 years) and four samples were in the Not Osteoporotic group (65-92 years).
      The indentation modulus and mineral to matrix ratio (mineral:matrix) were lower
      in the Osteoporotic group than the Not Osteoporotic group. Mineral:matrix ratio
      decreased with age (r (2) = 0.35, p = 0.05), and the indentation modulus
      increased with areal bone mineral density (r (2) = 0.41, p = 0.04). This study is
      the first to examine cancellous bone composition and mechanical properties from a
      fracture prone location with osteoporosis. We found differences in tissue
      composition and mechanical properties with osteoporosis that could contribute to
      increased fragility in addition to changes in trabecular architecture and bone
      volume. 

PMID- 24888693
TI  - Echocardiographic assessment of Ebstein's anomaly.
AB  - Ebstein's anomaly is a complex congenital lesion which primarily involves the
      tricuspid valve. The tricuspid leaflets are tethered to varying degrees to the
      right ventricular free wall and the ventricular septum often resulting in
      significant tricuspid regurgitation and a small functioning right ventricular
      chamber. Although the septal leaflet originates normally at the right
      atrioventricular junction, the proximal portion is often completely tethered to
      the ventricular septum resulting in a misconception and erroneous statements in
      many publications that its attachment is apically displaced. Although two
      dimensional echocardiography represents the primary modality for the diagnosis of
      this anomaly, three-dimensional echocardiography provides incremental value in
      characterizing the extent and severity of tethering of individual tricuspid valve
      leaflets. This information is useful in surgical decision making whether to
      repair or replace the tricuspid valve. 

PMID- 24888694
TI  - National and international guidelines for rectal cancer.
AB  - AIM: Rectal cancer is a common malignancy. Differences in daily practice may
      influence the morbidity and mortality, and many national and international
      organizations have created guidelines for staging and treatment of rectal cancer.
      Even though consensus is reached within individual guidelines, this might not be
      the case between guidelines. No formal evaluation of the contrasting guidance has
      been reported. METHOD: A systematic search for national and international
      guidelines on rectal cancer was performed. Eleven guidelines were identified for
      further analysis. RESULTS: There was no consensus concerning the definition of
      rectal cancer. Ten of the 11 guidelines use the TNM staging system and there was
      general agreement regarding the recommendation of MRI and CT in rectal cancer.
      There was consensus concerning a multidisciplinary approach, preoperative
      chemoradiotherapy (CRT) and total mesorectal excision (TME). There was no
      consensus concerning local treatment of T1 tumours and adjuvant therapy, and not
      all guidelines included metastatic disease and recurrence. There was no consensus
      on the protocol for follow up. The guidelines had different approaches to
      evidence. All referred to evidence but not all considered the level of evidence.
      CONCLUSION: The intention of the study was to provide an overview of
      international guidelines for rectal cancer based on the underlying evidence, but
      despite hard evidence it was very difficult to reach general conclusions. Despite
      much knowledge, there is no international consensus on guidelines for the staging
      and treatment of rectal cancer.

PMID- 24888695
TI  - Genome diversity in Brachypodium distachyon: deep sequencing of highly diverse
      inbred lines.
AB  - Brachypodium distachyon is small annual grass that has been adopted as a model
      for the grasses. Its small genome, high-quality reference genome, large germplasm
      collection, and selfing nature make it an excellent subject for studies of
      natural variation. We sequenced six divergent lines to identify a comprehensive
      set of polymorphisms and analyze their distribution and concordance with gene
      expression. Multiple methods and controls were utilized to identify polymorphisms
      and validate their quality. mRNA-Seq experiments under control and simulated
      drought-stress conditions, identified 300 genes with a genotype-dependent
      treatment response. We showed that large-scale sequence variants had extremely
      high concordance with altered expression of hundreds of genes, including many
      with genotype-dependent treatment responses. We generated a deep mRNA-Seq dataset
      for the most divergent line and created a de novo transcriptome assembly. This
      led to the discovery of >2400 previously unannotated transcripts and hundreds of
      genes not present in the reference genome. We built a public database for
      visualization and investigation of sequence variants among these widely used
      inbred lines.

PMID- 24888696
TI  - Coming of age: is it now time for paediatrics to form its own college?

PMID- 24888697
TI  - Automated quantification of apoptosis in B-cell chronic lymphoproliferative
      disorders: a prognostic variable obtained with the Cell-Dyn Sapphire (Abbott)
      automated hematology analyzer.
AB  - INTRODUCTION: B-chronic lymphocytic leukemia CLL, a neoplastic clonal disorder
      with monomorphous small B lymphocytes with scanty cytoplasm and clumped
      chromatin, can be morphologically differentiated in typical and atypical forms
      with different prognosis: Smudge cells (Gumprecht's shadows) are one of the well
      known features of the typical CLL and are much less inconsistent in other
      different types CLPD. Abbott Cell-Dyn Sapphire uses the fluorescence after
      staining with the DNA fluorochrome propidium iodide for the measurement of
      nucleated red blood cells (NRBCs) and nonviable cells (FL3+ cell fraction): We
      have studied the possible correlation between presence and number of
      morphologically identifiable smudge cells on smears and the percentage of
      nonviable cells produced by Cell-Dyn Sapphire. METHODS: 305 blood samples from
      224 patients with B-cell lymphoproliferative disorders and 40 healthy blood
      donors were analyzed by CBC performed by Cell-Dyn Sapphire, peripheral blood
      smear, and immunophenotype characterization. RESULT: FL3+ fraction in CLPD
      directly correlated with the percentage of smudge cells and is significantly
      increased in patients with typical B-CLL. This phenomenon is much less evident in
      patients with atypical/mixed B-CLL and B-NHL. CONCLUSION: In small laboratories
      without FCM and cytogenetic, smudge cells%, can be utilized as a preliminary
      diagnostic and prognostic tool in differential diagnosis of CLPD.

PMID- 24888698
TI  - Transungual delivery: deliberations and creeds.
AB  - Although considered as trifling illness, nail diseases have a reasonably high
      occurrence and a noteworthy impact on the patients' quality of life. Furthermore,
      there is a need to improve the topical treatment for nail diseases to avoid drug
      interactions and to reduce side effects associated with oral therapy. Topical
      drug delivery to the nails has established amplified consideration lately.
      Strategies (such as chemical enhancers, formulation strategies, physical and
      mechanical methods) are being investigated in order to improve drug permeability
      across the nail plate. The rationale of this review is to present contemporary
      information on the structure of human nail along with its comparison with animal
      hooves. Precincts of nail permeability have been briefly discussed with respect
      to factors like permeant's molecular size, hydrophilicity, charge and the nature
      of the vehicle. These factors affect drug uptake and permeation through the nail.
      Formulations like nail lacquers which mimic cosmetic varnish and colloidal
      carriers along with nail substitutes that can be utilized for transungual
      delivery have also been discussed. 

PMID- 24888699
TI  - Helical DNA origami tubular structures with various sizes and arrangements.
AB  - We developed a novel method to design various helical tubular structures using
      the DNA origami method. The size-controlled tubular structures which have 192,
      256, and 320 base pairs for one turn of the tube were designed and prepared. We
      observed the formation of the expected short tubes and unexpected long ones.
      Detailed analyses of the surface patterns of the tubes showed that the short
      tubes had mainly a left-handed helical structure. The long tubes mainly formed a
      right-handed helical structure and extended to the directions of the double
      helical axes as structural isomers of the short tubes. The folding pathways of
      the tubes were estimated by analyzing the proportions of short and long tubes
      obtained at different annealing conditions. Depending on the number of base pairs
      involved in one turn of the tube, the population of left-/right-handed and
      short/long tubes changed. The bending stress caused by the stiffness of the
      bundled double helices and the non-natural helical pitch determine the structural
      variety of the tubes. 

PMID- 24888700
TI  - Organic nonlinear optical materials: the mechanism of intermolecular covalent
      bonding interactions of Kekule hydrocarbons with significant singlet biradical
      character.
AB  - The ground- and excited-state properties of benzene-linked bisphenalenyl (B-LBP),
      naphthaline-linked bisphenalenyl (N-LBP), and anthracene-linked bisphenalenyl (A
      LBP) Kekule molecules and their respective one-dimensional (1D) stacks are
      investigated using time-dependent density functional theory (TD-DFT) and a range
      of extensive multidimensional visualization techniques. The results reveal a
      covalent pi-pi bonding interaction between overlapping phenalenyl radicals whose
      bond length is shorter than the van der Waals distance between carbon atoms.
      Increasing the linker length and/or number of molecules involved in the 1D stack
      decreases the HOMO-LUMO energy gap and increases the wavelength of the systems.
      The charge-transfer mechanism and electron coherence both differ with changes in
      the linker length and/or number of molecules involved in the 1D stack. 

PMID- 24888701
TI  - Letter to the editor.

PMID- 24888702
TI  - Evaluation of osteogenic cell differentiation in response to bone morphogenetic
      protein or demineralized bone matrix in a critical sized defect model using GFP
      reporter mice.
AB  - We evaluated the osteoprogenitor response to rhBMP-2 and DBM in a transgenic
      mouse critical sized defect. The mice expressed Col3.6GFPtopaz (a pre
      osteoblastic marker), Col2.3GFPemerald (an osteoblastic marker) and alpha-smooth
      muscle actin (alpha-SMA-Cherry, a pericyte/myofibroblast marker). We assessed
      defect healing at various time points using radiographs, frozen, and conventional
      histologic analyses. GFP signal in regions of interest corresponding to the areas
      of new bone formation was quantified using a novel computer assisted algorithm.
      All defects treated with rhBMP-2 healed. In contrast, the majority of the defects
      in the DBM (27/30) and control (28/30) groups did not heal. Quantitation of pre
      osteoblasts demonstrated a maximal response (% GFP + cells/TV) in the
      Col3.6GFPtopaz mice at day 7 (7.2% +/- 6.0, p < 0.05 compared to days 14, 21, 28,
      and 56). The maximal response of the Col2.3GFP cells was seen at days 14 (8.04%
      +/- 5.0) and 21 (8.31% +/- 4.32), p < 0.05. In contrast, DBM and control groups
      showed a limited osteogenic response at all time points. In conclusion, we
      demonstrated that the BMP and DBM induce vastly different osteogenic responses
      which should influence their clinical application as bone graft substitutes.

PMID- 24888703
TI  - Assessment of the consistency of national-level policies and guidelines for
      malaria in pregnancy in five African countries.
AB  - BACKGROUND: At least 39 sub-Saharan African countries have policies on preventing
      malaria in pregnancy (MIP), including use of long-lasting insecticidal nets
      (LLINs), intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp
      SP) and case management. However, coverage of LLINs and IPTp-SP remains below
      international targets in most countries. One factor contributing to low coverage
      may be that MIP policies typically are developed by national malaria control
      programmes (NMCPs), but are implemented through national reproductive health (RH)
      programmes. METHODS: National-level MIP policies, guidelines, and training
      documents from NMCPs and RH programmes in Kenya, Mali, Mozambique, mainland
      Tanzania and Uganda were reviewed to assess whether they reflected WHO guidelines
      for prevention and treatment of MIP, and how consistent MIP content was across
      documents from the same country. Documents were compared for adherence to WHO
      guidance concerning IPTp-SP timing and dose, directly observed therapy, promotion
      and distribution of LLINs, linkages to HIV programmes and MIP case management.
      RESULTS: The five countries reviewed had national documents promoting IPTp-SP,
      LLINs and MIP case management. WHO guidance from 2004 frequently was not
      reflected: four countries recommended the first dose of IPTp-SP at 20 weeks or
      later (instead of 16 weeks), and three countries restricted the first and second
      IPTp-SP doses to specific gestational weeks. Documents from four countries
      provided conflicting guidance on MIP prevention for HIV-positive women, and none
      provided complete guidance on management of uncomplicated and severe malaria
      during pregnancy. In all countries, inconsistencies between NMCPs and RH
      programmes on the timing or dose of IPTp-SP were documented, as was the mechanism
      for providing LLINs. Inconsistencies also were found in training documents from
      NMCPs and RH programmes in a given country. Outdated, inconsistent guidelines
      have the potential to cause confusion and lead to incorrect practices among
      health workers who implement MIP programmes, contributing to low coverage of IPTp
      SP and LLINs. CONCLUSIONS: MIP policies, guidelines and training materials are
      outdated and/or inconsistent in the countries assessed. Updating and ensuring
      consistency among national MIP documents is needed, along with re-orientation and
      supervision of health workers to accelerate implementation of the 2012 WHO Global
      Malaria Programme policy recommendations for IPTp-SP.

PMID- 24888706
TI  - Phenolic compounds in fresh and dried figs from Cilento (Italy), by considering
      breba crop and full crop, in comparison to Turkish and Greek dried figs.
AB  - Fresh and dried figs are important components of the Mediterranean diet. In
      Cilento (Southern Italy), figs belonging to cultivar "Dottato" are used for the
      production of "PDO Cilento white figs," as dried figs. In this article, we
      reported the characterization of the phenolic compounds in 19 fig samples: 9
      fresh figs cultivar "Dottato" from Cilento (Italy), 10 dried fig samples from
      Cilento (2), Turkey (6), and Greece (2). The following phenolic compounds were
      identified and quantified by high-performance liquid chromatography (HPLC)/UV
      DAD: chlorogenic acid, protocatechuic acid, vanillic acid, luteolin-3,7-di-O
      glucoside, luteolin 7-glucoside, apigenin-7-O-rutinoside, rutin, quercetin-3
      glucoside, and cyanidin-3-O-rutinoside. A discriminative analysis between the
      peel and pulp of the samples was carried out. The 1st crop ("breba") and the 2nd
      one (full crop) from Dottato figs were considered, as well as the effect of fig
      pollination. The majority of the phenolic compounds were predominant in the fig
      peel. Significant quantitative differences were found among fresh figs, whereas
      also some qualitative differences were obtained between fresh and dried figs from
      the same origin in Dottato cultivar, and among dried figs from different origins.
      Breba crop resulted richer in phenolics than figs of the 2nd crop. Considering
      the dried figs, the Turkish ones had the highest concentration in phenolic
      compounds. Other compounds such as the aminoacids tyrosine and tryptophan were
      also detected by HPLC-DAD analysis in Dottato figs, probably due to the
      similarity of their chemical structure. PRACTICAL APPLICATION: The results of
      this research could be useful to deepen the knowledge about the phenolic
      composition of a fruit that is particularly appreciated in Mediterranean area and
      presents an increasing interest worldwide. We also characterized a typical
      Italian fig (Cilento Dottato) that has relevant economical importance in Southern
      Italy; thus, our work could be applied by producers and industries for the
      valorization of dried figs as high-quality products. From the consumer viewpoint,
      a comparison among dried figs from different origins found on the retail market
      has a huge significance to inform about what the market offers and what product
      is the richest one in polyphenol content.

PMID- 24888705
TI  - Comparing clinical attachment level and pocket depth for predicting periodontal
      disease progression in healthy sites of patients with chronic periodontitis using
      multi-state Markov models.
AB  - AIM: To understand degeneration of healthy sites and identify factors associated
      with disease progression in patients with chronic periodontitis. MATERIAL AND
      METHODS: Data on healthy sites from 163 American and Swedish subjects were
      analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov
      models based on bleeding on probing (BOP), and either clinical attachment level
      (CAL) + BOP or pocket depth (PD) + BOP. RESULTS: In 2 years, 10% (CAL + BOP) and
      3% (PD + BOP) of healthy sites developed chronic periodontitis. On average,
      healthy sites remained healthy for 32 months before transiting in both models.
      Most transitions (87-97%) from health were to the gingivitis state. The expected
      duration of the gingivitis lesion was 4-5 months and sites recovered with a high
      probability (96-98%). Disease severity as measured by number of sites with CAL/PD
      > 4 mm at baseline and smoking, were associated with fast progression from health
      to chronic periodontitis within 6 months as were gingival redness in the PD + BOP
      model only. With age, the rate of disease progression to gingivitis decreased.
      CONCLUSION: Transition probabilities for gingivitis and chronic periodontitis
      were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were
      significant predictors for fast progression.

PMID- 24888708
TI  - Short-term variations in gene flow related to cyclic density fluctuations in the
      common vole.
AB  - In highly fluctuating populations with complex social systems, genetic patterns
      are likely to vary in space and time due to demographic and behavioural
      processes. Cyclic rodents are extreme examples of demographically instable
      populations that often exhibit strong social organization. In such populations,
      kin structure and spacing behaviour may vary with density fluctuations and impact
      both the composition and spatial structure of genetic diversity. In this study,
      we analysed the multiannual genetic structure of a cyclic rodent, Microtus
      arvalis, using a sample of 875 individuals trapped over three complete cycles
      (from 1999 to 2007) and genotyped at 10 microsatellite loci. We tested the
      predictions that genetic diversity and gene flow intensity vary with density
      fluctuations. We found evidences for both spatial scale-dependant variations in
      genetic diversity and higher gene flow during high density. Moreover,
      investigation of sex-specific relatedness patterns revealed that, although
      dispersal is biased toward males in this species, distances moved by both sexes
      were lengthened during high density. Altogether, these results suggest that an
      increase in migration with density allows to restore the local loss of genetic
      diversity occurring during low density. We then postulate that this change in
      migration results from local competition, which enhances female colonization of
      empty spaces and male dispersal among colonies.

PMID- 24888707
TI  - Nimbolide inhibits IGF-I-mediated PI3K/Akt and MAPK signalling in human breast
      cancer cell lines (MCF-7 and MDA-MB-231).
AB  - The insulin-like growth factor I (IGF-I) signalling pathway contributes a major
      role on various cancer cell proliferation, survival and cell cycle. The present
      study was aimed to investigate the effect of nimbolide on IGF signalling and cell
      cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines. The protein
      expression of IGF signalling molecules and cell cycle protein levels was assessed
      by western blot analysis. In order to study the interaction of nimbolide on IGF-1
      signalling pathway, IGF-I and phosphoinositide 3-kinase (PI3K) inhibitor
      (LY294002) were used to treat MCF-7 and MDA-MB-231 cells. Further, the cell cycle
      arrest was analysed by flow cytometry. The protein expression of IGF signalling
      molecules was significantly decreased in nimbolide-treated breast cancer cells.
      PI3K inhibitor and IGF-I with nimbolide treatment notably inhibited
      phosphorylated Akt. The cell cycle arrest was observed at the G0/G1 phase, and
      accumulation of apoptotic cells was observed in nimbolide-treated breast cancer
      cell lines. Nimbolide also increased the protein expression of p21 and decreased
      the cyclins in both the cell lines. Nimbolide decreases the proliferation of
      breast cancer cells by modulating the IGF signalling molecules, which could be
      very useful for the breast cancer treatment.

PMID- 24888710
TI  - Vision impairment and dual sensory problems in middle age.
AB  - PURPOSE: Vision and hearing impairments are known to increase in middle age. In
      this study we describe the prevalence of vision impairment and dual sensory
      impairment in UK adults aged 40-69 years in a very large and recently ascertained
      data set. The associations between vision impairment, age, sex, socioeconomic
      status, and ethnicity are reported. METHODS: This research was conducted using
      the UK Biobank Resource, with subsets of UK Biobank data analysed with respect to
      self-report of eye problems and glasses use. Better-eye visual acuity with
      habitually worn refractive correction was assessed with a logMAR chart (n =
      116,682). Better-ear speech reception threshold was measured with an adaptive
      speech in noise test, the Digit Triplet Test (n = 164,770). Prevalence estimates
      were weighted with respect to UK 2001 Census data. RESULTS: Prevalence of mild
      visual impairment (VA >0.1 logMAR (6/7.5, 20/25) and >=0.48 (6/18, 20/60)) and
      low vision (VA >0.48 (6/18, 20/60) and >=1.3 (6/120, 20/400)) was estimated at
      13.1% (95% CI 12.9-13.4) and 0.8% (95% CI 0.7-0.9), respectively. Use of glasses
      was 88.0% (95% CI 87.9-88.1). The prevalence of dual sensory impairment was 3.1%
      (95% CI 3.0-3.2) and there was a nine-fold increase in the prevalence of dual
      sensory problems between the youngest and oldest age groups. Older adults, those
      from low socioeconomic and ethnic minority backgrounds were most at risk for
      vision problems. CONCLUSIONS: Mild vision impairment is common in middle aged UK
      adults, despite widespread use of spectacles. Increased likelihood of vision
      impairment with older age and with ethnic minorities is of concern given ageing
      and more ethnically diverse populations. Possible barriers to optometric care for
      those from low socioeconomic and ethnic minority backgrounds may require
      attention. A higher than expected prevalence of dual impairment suggests that
      hearing and vision problems share common causes. Optometrists should consider
      screening for hearing problems, particularly among older adults.

PMID- 24888711
TI  - Interrater agreement for Critical Care EEG Terminology.
AB  - OBJECTIVE: The interpretation of critical care electroencephalography (EEG)
      studies is challenging because of the presence of many periodic and rhythmic
      patterns of uncertain clinical significance. Defining the clinical significance
      of these patterns requires standardized terminology with high interrater
      agreement (IRA). We sought to evaluate IRA for the final, published American
      Clinical Neurophysiology Society (ACNS)-approved version of the critical care EEG
      terminology (2012 version). Our evaluation included terms not assessed previously
      and incorporated raters with a broad range of EEG reading experience. METHODS:
      After reviewing a set of training slides, 49 readers independently completed a
      Web-based test consisting of 11 identical questions for each of 37 EEG samples
      (407 questions). Questions assessed whether a pattern was an electrographic
      seizure; pattern location (main term 1), pattern type (main term 2); and presence
      and classification of eight other key features ("plus" modifiers, sharpness,
      absolute and relative amplitude, frequency, number of phases,
      fluctuation/evolution, and the presence of "triphasic" morphology). RESULTS: IRA
      statistics (kappa values) were almost perfect (90-100%) for seizures, main terms
      1 and 2, the +S modifier (superimposed spikes/sharp waves or sharply contoured
      rhythmic delta activity), sharpness, absolute amplitude, frequency, and number of
      phases. Agreement was substantial for the +F (superimposed fast activity) and +R
      (superimposed rhythmic delta activity) modifiers (66% and 67%, respectively),
      moderate for triphasic morphology (58%), and fair for evolution (21%).
      SIGNIFICANCE: IRA for most terms in the ACNS critical care EEG terminology is
      high. These terms are suitable for multicenter research on the clinical
      significance of critical care EEG patterns. A PowerPoint slide summarizing this
      article is available for download in the Supporting Information section
      http://dx.doi.org/10.1111/epi.12653/supinfo.

PMID- 24888709
TI  - Human cytomegalovirus tropism for mucosal myeloid dendritic cells.
AB  - Human CMV infections are a serious source of morbidity and mortality for
      immunocompromised patients and for the developing fetus. Because of this, the
      development of new strategies to prevent CMV acquisition and transmission is a
      top priority. Myeloid dendritic cells (DC) residing in the oral and nasal mucosae
      are among the first immune cells to encounter CMV during entry and greatly
      contribute to virus dissemination, reactivation from latency, and horizontal
      spread. Albeit affected by the immunoevasive tactics of CMV, mucosal DC remain
      potent inducers of cellular and humoral immune responses against this virus.
      Their natural functions could thus be exploited to generate long-lasting
      protective immunity against CMV by vaccination via the oronasal mucosae. Although
      related, epithelial Langerhans-type DC and dermal monocyte-derived DC interact
      with CMV in dramatically different ways. Whereas immature monocyte-derived DC are
      fully permissive to infection, for instance, immature Langerhans-type DC are
      completely resistant. Understanding these differences is essential to design
      innovative vaccines and new antiviral compounds to protect these cells from CMV
      infection in vivo.

PMID- 24888713
TI  - Boron diiminate with aggregation-induced emission and crystallization-induced
      emission-enhancement characteristics.
AB  - Organoboron complexes having aggregation- and crystalization-induced emission
      properties are presented. The series of boron diiminates were synthesized and the
      emission behaviors of the synthesized compounds were investigated. Finally, it
      was found that significant enhancement of the emission depended on the
      crystallinity in the solid states. 

PMID- 24888712
TI  - CHOPPI: a web tool for the analysis of immunogenicity risk from host cell
      proteins in CHO-based protein production.
AB  - Despite high quality standards and continual process improvements in
      manufacturing, host cell protein (HCP) process impurities remain a substantial
      risk for biological products. Even at low levels, residual HCPs can induce a
      detrimental immune response compromising the safety and efficacy of a biologic.
      Consequently, advanced-stage clinical trials have been cancelled due to the
      identification of antibodies against HCPs. To enable earlier and rapid assessment
      of the risks in Chinese Hamster Ovary (CHO)-based protein production of residual
      CHO protein impurities (CHOPs), we have developed a web tool called CHOPPI, for
      CHO Protein Predicted Immunogenicity. CHOPPI integrates information regarding the
      possible presence of CHOPs (expression and secretion) with characterizations of
      their immunogenicity (T cell epitope count and density, and relative conservation
      with human counterparts). CHOPPI can generate a report for a specified CHO
      protein (e.g., identified from proteomics or immunoassays) or characterize an
      entire specified subset of the CHO genome (e.g., filtered based on confidence in
      transcription and similarity to human proteins). The ability to analyze potential
      CHOPs at a genomic scale provides a baseline to evaluate relative risk. We show
      here that CHOPPI can identify clear differences in immunogenicity risk among
      previously validated CHOPs, as well as identify additional "risky" CHO proteins
      that may be expressed during production and induce a detrimental immune response
      upon delivery. We conclude that CHOPPI is a powerful tool that provides a
      valuable computational complement to existing experimental approaches for CHOP
      risk assessment and can focus experimental efforts in the most important
      directions. Biotechnol. Bioeng. 2014;111: 2170-2182. (c) 2014 Wiley Periodicals,
      Inc. 

PMID- 24888714
TI  - Canalization and developmental instability of the fetal skull in a mouse model of
      maternal nutritional stress.
AB  - Nutritional imbalance is one of the main sources of stress in both extant and
      extinct human populations. Restricted availability of nutrients is thought to
      disrupt the buffering mechanisms that contribute to developmental stability and
      canalization, resulting in increased levels of fluctuating asymmetry (FA) and
      phenotypic variance among individuals. However, the literature is contradictory
      in this regard. This study assesses the effect of prenatal nutritional stress on
      FA and among-individual variance in cranial shape and size using a mouse model of
      maternal protein restriction. Two sets of landmark coordinates were digitized in
      three dimensions from skulls of control and protein restricted specimens at E17.5
      and E18.5. We found that, by the end of gestation, maternal protein restriction
      resulted in a significant reduction of skull size. Fluctuating asymmetry in size
      and shape exceeded the amount of measurement error in all groups, but no
      significant differences in the magnitude of FA were found between treatments.
      Conversely, the pattern of shape asymmetry was affected by the environmental
      perturbation since the angles between the first eigenvectors extracted from the
      covariance matrix of shape asymmetric component of protein restricted and control
      groups were not significantly different from the expected for random vectors. In
      addition, among-individual variance in cranial shape was significantly higher in
      the protein restricted than the control group at E18.5. Overall, the results
      obtained from a controlled experiment do not support the view of fluctuating
      asymmetry of cranial structures as a reliable index for inferring nutritional
      stress in human populations.

PMID- 24888715
TI  - Modulation of the inflammation-coagulation interaction during pneumococcal
      pneumonia by immunobiotic Lactobacillus rhamnosus CRL1505: role of Toll-like
      receptor 2.
AB  - The present study evaluated the effect of nasally given Lactobacillus rhamnosus
      CRL1505 on the immunocoagulative response during pneumococcal infection in
      immunocompetent mice. In addition, we aimed to gain insight into the mechanism
      involved in the immunomodulatory effect of the L. rhamnosus CRL1505 strain by
      evaluating the role of TLR2. Results showed that nasally given L. rhamnosus
      CRL1505 effectively regulates inflammation and hemostatic alterations during the
      pneumococcal infection. Immunobiotic treatment significantly reduced permeability
      of the bronchoalveolar-capillary barrier, and general cytotoxicity, decreasing
      lung tissue damage. The CRL1505 strain improved the production of TNF-alpha, IFN
      gamma, and IL-10 after pneumococcal challenge. In addition, increased TM and TF
      expressions were found in lungs of L. rhamnosus CRL1505-treated mice. Moreover,
      we demonstrated, for the first time, that the TLR2 signaling pathway has a role
      in the induction of IFN-gamma and IL-10 and in the reduction of TF. The results
      also allow us to speculate that a PRR, other than TLR2, may mediate the
      immunobiotic activity of L. rhamnosus CRL1505 and could explain changes in TNF
      alpha and TM.

PMID- 24888716
TI  - The effects of endothelial progenitor cells on rat atherosclerosis.
AB  - Atherosclerosis (AS) is a progressive disease characterized by endothelial injury
      and lipid aggregation in the arterial walls. Studies have reported that
      endothelial progenitor cells (EPCs) derived from the bone marrow (BM) might
      provide an endogenous repair mechanism by differentiating into endothelial cells
      to replace the dysfunctional endothelium. Our study aims to investigate the
      effect of EPCs derived from rat BM on AS. EPCs transduced by recombinant adeno
      associated virus-green fluorescent protein (GFP) were transplanted into a rat AS
      model. After 2 months of transplantation, the localization of GFP-labeled cells,
      morphology, and lipid content in the aorta were examined. GFP-labeled EPCs were
      found in the endothelial monolayer of the artery vessel in the GFP/EPC group.
      Hematoxylin and eosin staining suggested that the lipid deposits in the aortic
      endothelium in the EPC/GFP group were less compared with those in the untreated
      group. Oil Red O staining of liver slices showed that lipid droplets were
      obviously decreased in the GFP/EPC group. The endothelial nitric oxide synthase
      and apolipoprotein E mRNA levels in the GFP/EPC group were significantly higher,
      but the intercellular cell adhesion molecule-1 mRNA level was significantly lower
      compared with the control group. The results suggest that EPCs derived from the
      BM can repair the injured endothelium and promote an atherosclerotic lesion
      regression. Therefore, EPCs may provide a useful tool for the treatment of AS. 

PMID- 24888717
TI  - Huperzine A attenuates hepatic ischemia reperfusion injury via anti-oxidative and
      anti-apoptotic pathways.
AB  - Hepatic ischemia reperfusion (HI/R) injury may occur during liver transplantation
      and remains a serious concern in clinical practice. Huperzine A (HupA), an
      alkaloid isolated from the Chinese traditional medicine Huperzia serrata, has
      been demonstrated to possess anti-oxidative and anti-apoptotic properties. In the
      present study, a rat model of HI/R was established by clamping the hepatic
      artery, the hepatoportal vein and the bile duct with a vascular clamp for 30 min
      followed by reperfusion for 6 h under anesthesia. HupA was injected into the tail
      vein 5 min prior to the induction of HI/R at doses of 167 and 500 ug/kg. The
      histopathological assessment of the liver was performed using hematoxylin and
      eosin staining. Alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) were assayed in the serum samples. The tissue levels of superoxide
      dismutase (SOD), catalase (CAT), malondiadehyde (MDA) and glutathione (GSH) were
      also measured spectrophotometrically. Furthermore, the protein expression of
      caspase-3, Bcl-2 and Bax in hepatic tissues was detected via western blot
      analysis. Treatment of Wistar rats with HupA at doses of 167 and 500 ug/kg
      markedly attenuated HI/R injury as observed histologically. In addition, the
      significant reductions of serum ALT and AST were observed in HupA-treated
      ischemic rats. Furthermore, HupA treatment enhanced the activity of hepatic
      tissue SOD, CAT and GSH, but decreased the MDA tissue content. Western blot
      analysis revealed elevated levels of Bcl-2 expression but decreased Bax and
      caspase-3 tissue expression at the protein level in the HupA-treated group. The
      present data suggest that HupA attenuates the HI/R injury of rats through its
      anti-oxidative and anti-apoptotic signaling pathways. 

PMID- 24888718
TI  - Altered immune proteome of Staphylococcus aureus under iron-restricted growth
      conditions.
AB  - Staphylococcus aureus is one of the major causative agents of severe infections,
      and is responsible for a high burden of morbidity and mortality. Strains of
      increased virulence have emerged (e.g. USA300) that can infect healthy
      individuals in the community and are difficult to treat. To add to the knowledge
      about the pathophysiology of S. aureus, the adaption to iron restriction, an
      important in vivo stressor, was studied and the corresponding immune response of
      the human host characterized. Using a combination of 1D and 2D immune proteomics,
      the human antibody response to the exoproteomes of S. aureus USA300Deltaspa grown
      under iron restriction or with excess iron was compared. Human antibody binding
      to the altered exoproteome under iron restriction showed a 2.7- to 6.2-fold
      increase in overall signal intensity, and new antibody specificities appeared.
      Quantification of the secreted bacterial proteins by gel-free proteomics showed
      the expected strong increase in level of proteins involved in iron acquisition
      during iron-restricted growth compared to iron access. This was accompanied by
      decreased levels of superantigens and hemolysins. The latter was corroborated by
      functional peripheral blood mononuclear cell proliferation assays. The present
      data provide a comprehensive view of S. aureus exoproteome adaptation to iron
      restriction. Adults have high concentrations of serum antibodies specific for
      some of the newly induced proteins. We conclude that iron restriction is a common
      feature of the microenvironment, where S. aureus interacts with the immune system
      of its human host. 

PMID- 24888719
TI  - A critical analysis of candidacy for penile revascularization.
AB  - INTRODUCTION: Penile revascularization (PR) is a potentially curative procedure
      for young men with isolated arteriogenic erectile dysfunction. Standard
      preoperative evaluation is erectile hemodynamics (HDX) using duplex Doppler
      penile ultrasound (DUS) and/or cavernosometry (DIC) and assessment of cavernosal
      arterial anatomy by selective internal pudendal arteriography (SIPA). AIM: The
      aim of this study was to review our experience with men who sought a second
      opinion from us regarding their candidacy for PR. METHOD: Study population
      consisted of men (i) who presented to us for a second opinion regarding PR; (ii)
      who had DUS/DIC and SIPA; and (iii) had been advised by outside surgeon to
      undergo PR. Review of the HDX study and SIPA was conducted. Discrepancies between
      these studies resulted in repeating the DIC in men with normal SIPA or repeating
      the SIPA in men with normal HDX studies. MAIN OUTCOME MEASURES: Discrepancies
      between HDX and SIPA and the results of repeat HDX or SIPA were the main outcome
      measures. RESULT: Forty-five patients participated in the study; mean age was 33
      years with 4% >=50 years old. Median vascular risk factor number was 1 (ranged 0
      3). A credible trauma history was present in 11%. Thirty-three percent had prior
      DIC and 49% of patients had a significant discrepancy between HDX study and SIPA,
      including all patients seen by a community urologist. Thirty-eight percent had a
      discrepancy between side of abnormality on HDX and SIPA where both studies were
      abnormal (group A). Seven percent had abnormal HDX and normal SIPA (group B).
      Four percent had a normal HDX study with an abnormal SIPA (group C). Repeat DIC
      (n = 20) was conducted in groups A + B and was normal in 70% of cases. Repeat
      SIPA (n = 2) was conducted in group C and was normal in both patients.
      CONCLUSION: Almost one half of patients had a significant discrepancy between HDX
      and SIPA. Of these, 73% had normal repeat studies, making them no longer
      candidates for penile revascularization.

PMID- 24888721
TI  - Enhanced photocatalytic property of reduced graphene oxide/TiO2 nanobelt surface
      heterostructures constructed by an in situ photochemical reduction method.
AB  - A facile method is proposed to assemble graphene oxide (GO) on the surface of a
      TiO2 nanobelt followed by an in situ photocatalytic reduction to form reduced
      graphene oxide (rGO)/TiO2 nanobelt surface heterostructures. The special
      colloidal properties of GO and TiO2 nanobelt are exploited as well as the
      photocatalytic properties of TiO2 . Using water-ethanol solvent mixtures, GO
      nanosheets are tightly wrapped around the surface of the TiO2 nanobelts through
      an aggregation process and are then reduced in situ under UV-light irradiation to
      form rGO/TiO2 nanobelt surface heterostructures. The heterostructures enhance the
      separation of the photoinduced carriers, which results in a higher photocurrent
      due to the special electronic characteristics of rGO. Compared to TiO2 nanobelts,
      the rGO/TiO2 nanobelt surface heterostructures possess higher photocatalytic
      activity for the degradation of methyl orange and for the production of hydrogen
      from water, as well as excellent recyclability, with no loss of activity over
      five cycles. 

PMID- 24888720
TI  - Tanshinone IIA induces cytochrome c-mediated caspase cascade apoptosis in A549
      human lung cancer cells via the JNK pathway.
AB  - Tanshinone IIA (TSIIA), a natural diterpene quinone in the traditional Chinese
      medicinal herb Dan-Shen (Salvia miltiorrhiza), has extensively exerted antitumor
      activity in cellular and animal models. However, the molecular mechanisms
      underlying the antitumor effects of TSIIA remain largely unknown. The in vitro
      effects of TSIIA on apoptosis were investigated in A549 non-small cell lung
      cancer (NSCLC) cells. The data showed that TSIIA significantly suppressed the
      proliferation of A549 cells in a dose-dependent manner, with IC50 values of
      16.0+/-3.7 and 14.5+/-3.3 uM at 48 h as determined by Cell Counting Kit-8 (CCK-8)
      assay and clone formation assay, respectively. The change of mitochondrial
      morphology and the loss of mitochondrial membrane potential (MMP) were observed
      during the induction. Furthermore, TSIIA induced A549 cell apoptosis as confirmed
      by typical morphological changes, with cytochrome c release from the mitochondria
      and Bax translocation to the mitochondria. Caspase activity data indicated that
      TSIIA activated caspase-9 and caspase-3 of mitochondria-mediated apoptosis, but
      not caspase-8 of receptor-mediated apoptosis, which could be largely rescued by
      SP600125 (JNK inhibitor). Taken together, these findings provide the first
      evidence that TSIIA inhibits growth of NSCLC A549 cells, induces activation of
      JNK signaling and triggers caspase cascade apoptosis mediated by the release of
      cytochrome c, which provides a better understanding of the molecular mechanisms
      of TSIIA on lung cancer.

PMID- 24888723
TI  - Polymicrogyria: a common and heterogeneous malformation of cortical development.
AB  - Polymicrogyria (PMG) is one of the most common malformations of cortical
      development. It is characterized by overfolding of the cerebral cortex and
      abnormal cortical layering. It is a highly heterogeneous malformation with
      variable clinical and imaging features, pathological findings, and etiologies. It
      may occur as an isolated cortical malformation, or in association with other
      malformations within the brain or body as part of a multiple congenital anomaly
      syndrome. Polymicrogyria shows variable topographic patterns with the bilateral
      perisylvian pattern being most common. Schizencephaly is a subtype of PMG in
      which the overfolded cortex lines full-thickness clefts connecting the
      subarachnoid space with the cerebral ventricles. Both genetic and non-genetic
      causes of PMG have been identified. Non-genetic causes include congenital
      cytomegalovirus infection and in utero ischemia. Genetic causes include metabolic
      conditions such as peroxisomal disorders and the 22q11.2 and 1p36 continguous
      gene deletion syndromes. Mutations in over 30 genes have been found in
      association with PMG, especially mutations in the tubulin family of genes.
      Mutations in the (PI3K)-AKT pathway have been found in association PMG and
      megalencephaly. Despite recent genetic advances, the mechanisms by which
      polymicrogyric cortex forms and causes of the majority of cases remain unknown,
      making diagnostic and prenatal testing and genetic counseling challenging. This
      review summarizes the clinical, imaging, pathologic, and etiologic features of
      PMG, highlighting recent genetic advances.

PMID- 24888722
TI  - Abnormal cell proliferation in the p75NTR-positive basal cell compartment of the
      esophageal epithelium during squamous carcinogenesis.
AB  - The low affinity neurotrophin receptor p75NTR is known to be expressed in the
      mitotically quiescent basal layer (BL) of the normal esophageal epithelium. The
      aim of the present study was to detect oncogenic changes in the p75NTR-positive
      BL during esophageal squamous carcinogenesis. The normal epithelium (NE), low
      grade intraepithelial neoplasia (LGN), high-grade intraepithelial neoplasia
      (HGN), and esophageal squamous carcinoma (SCC), in which invasion was limited to
      the muscularis mucosa, were obtained from surgically removed esophagi. The
      expression of p75NTR, the proliferation marker ki67, hTERT, p53, and p63 was
      examined immunohistochemically. The expression of p75NTR was detected in these
      tissues with average staining indexes (number of stained cells/100 nucleated
      cells; SI) of 1.00, 0.99, 0.81, and 0.73, respectively. The expression of ki67 in
      the BL significantly increased with the progression from LGN to HGN. The
      expression of hTERT and p53 significantly increased with the progression from NE
      to LGN, and then increased in a stepwise manner in HGN and SCC, with SI
      (hTERT/p53) of 0.10/0.11, 0.32/0.45, 0.50/0.72, and 0.65/0.61, respectively. The
      expression of p63 showed no significant difference among NE, LGN, HGN, and SCC,
      with SI of 0.82, 0.77, 0.85, and 0.87, respectively. A correlation was observed
      between the expression of ki67 and p53 (P = 0.005), while a negative correlation
      was found between p75NTR and hTERT (P = 0.01). Our results demonstrated that
      phenotypic changes from quiescent to active proliferation in the p75NTR-positive
      BL occurred during the progression from LGN to HGN. The altered expression of
      hTERT and p53 in the BL was detected in LGN, which suggested that additional
      oncogenic events that disrupt mitotic regulation in the p75NTR-positive quiescent
      BL may play a crucial role in malignant transformation. Further investigations
      using the isolation and tracing of p75NTR-positive cells in precancerous
      epithelia may provide us with a better understanding of squamous carcinogenesis. 

PMID- 24888724
TI  - Bullying in preschool: The associations between participant roles, social
      competence, and social preference.
AB  - The different roles of bullying participation (bully, follower, victim, defender
      of the victim, and outsider) have not been investigated in preschool children.
      The aims of this study were to use a peer-report measure to assess these roles
      and to investigate their associations with social competence among pre-schoolers.
      We also explored whether status among peers, indicated by being socially
      preferred, mediates the relationship between social competence and bullying
      roles. Three hundred twenty 3- to 6-year-old children participated in the study.
      Bullying roles and social preference were assessed by means of peer reports,
      whereas social competence was investigated with a Q-Sort methodology, based on
      observations in classrooms. Bullying was also assessed by means of teacher
      reports. The results showed quite a clear distinction among roles and a
      correspondence between peer and teacher assessments, except for the role of
      outsider. The role of defender was positively associated with social competence,
      whereas the other roles were negatively associated. In a subsample, social
      preference statistically predicted the role of bully and mediated between social
      competence and bullying. The findings are discussed in terms of the importance of
      assessing bullying and its correlates at a very young age, although roles may
      further develop when children grow up.

PMID- 24888725
TI  - Gene expression profiling of laser microdissected airway smooth muscle tissue in
      asthma and atopy.
AB  - BACKGROUND: Asthma and atopy share common characteristics including type 2 helper
      T-cell-mediated inflammation. However, only asthma is associated with variable
      airways obstruction. The complex cellular and molecular pathways distinguishing
      asthma and atopy can now be captured by transcriptomic analysis (RNA-Seq). We
      hypothesized that the transcriptomic profile of airway smooth muscle (ASM)
      distinguishes atopic asthma from atopic healthy controls. First, we compared the
      ASM transcriptomic profiles of endobronchial biopsies between glucocorticoid
      free, atopic asthma patients, and atopic and nonatopic healthy controls. Second,
      we investigated the association between ASM transcriptomic profiles and airway
      function. METHODS: Twelve asthma patients and 12 control subjects (six atopic,
      six nonatopic) underwent bronchoscopy. RNA of laser-dissected ASM from 96
      bronchial biopsy specimens was sequenced with Roche GS FLX. Gene networks were
      identified using Ingenuity Pathway Analysis. RNA-Seq reads were assumed to follow
      a negative binomial distribution. With the current sample size, the estimated
      false discovery rate was approximately 1%. RESULTS: One hundred and seventy four
      ASM genes were differentially expressed between asthma patients and atopic
      controls, 108 between asthma patients and nonatopic controls, and 135 between
      atopic and nonatopic controls. A set of eight genes discriminated asthma patients
      from nonasthmatic controls, irrespective of atopy. Four of these genes (RPTOR,
      VANGL1, FAM129A, LEPREL1) were associated with airway hyper-responsiveness (P <
      0.05). CONCLUSION: Airway smooth muscle from asthma patients can be distinguished
      from that of atopic and nonatopic control subjects by a specific gene expression
      profile, which is associated with airway hyper-responsiveness.

PMID- 24888727
TI  - The modular structure of ThDP-dependent enzymes.
AB  - Thiamine diphosphate (ThDP)-dependent enzymes form a diverse protein family which
      was classified into nine superfamilies. The cofactor ThDP is bound at the
      interface between two catalytic domains, the PYR and the PP domain. The nine
      superfamilies were assigned to five different structural architectures. Two
      superfamilies, the sulfopyruvate decarboxylases and alpha-ketoacid dehydrogenases
      2, consist of separate PYR and PP domains. The oxidoreductase superfamily is of
      the intra-monomer/PYR-PP type with an N-terminal PYR and a subsequent PP domain.
      The active enzymes form homodimers with the ThDP cofactor bound at the interface
      between a PYR and a PP domain of the same monomer. Decarboxylases are of the
      inter-monomer/PYR-PP type with the cofactor bound between domains from different
      monomers. 1-Deoxy-d-xylulose-5-phosphate synthases are of the intra-monomer/PP
      PYR type. The transketolases, alpha-ketoglutarate dehydrogenases, and alpha
      ketoacid dehydrogenases 1 are of the inter-monomer/PP-PYR type. For the
      phosphonopyruvate decarboxylases, definitive assessment of the structural
      architecture is not possible due to lack of structure information. By applying a
      structure-based domain alignment method, sequences of more than 62,000 PYR and PP
      domains were identified and aligned. Although the sequence similarity of the
      catalytic domains is low between different superfamilies, seven positions were
      identified to be highly conserved, including the cofactor binding GDGX(24,27) N
      motif, the cofactor-activating glutamic acid, and two structurally equivalent
      glycines in both the PYR and the PP domain. An evolutionary pathway of ThDP
      dependent enzymes is proposed which explains the sequence and structure diversity
      of this family by three basic evolutionary events: domain recruitment, domain
      linkage, and structural rearrangement of catalytic domains.

PMID- 24888726
TI  - Arabidopsis cytosolic alpha-glycan phosphorylase, PHS2, is important during
      carbohydrate imbalanced conditions.
AB  - Arabidopsis thaliana has two isoforms of alpha-glycan phosphorylase (EC 2.4.1.1),
      one residing in the plastid and the other in the cytosol. The cytosolic
      phosphorylase, PHS2, acts on soluble heteroglycans that constitute a part of the
      carbohydrate pool in a plant. This study aimed to define a physiological role for
      PHS2. Under standard growth conditions phs2 knock-out mutants do not show any
      clear growth phenotype, and we hypothesised that during low-light conditions
      where carbohydrate imbalance is perturbed, this enzyme is important. Soil-grown
      phs2 mutant plants developed leaf lesions when placed in very low light. Analysis
      of soluble heteroglycan (SHG) levels showed that the amount of glucose residues
      in SHG was higher in the phs2 mutant compared to wild-type plants. Furthermore, a
      standard senescence assay from soil-grown phs2 mutant plants showed that leaves
      senesced significantly faster in darkness than the wild-type leaves. We also
      found decreased hypocotyl extension in in vitro-grown phs2 mutant seedlings when
      grown for long time in darkness at 6  degrees C. We conclude that PHS2 activity
      is important in the adult stage during low-light conditions and senescence, as
      well as during prolonged seedling development when carbohydrate levels are
      unbalanced. 

PMID- 24888728
TI  - Fostering interprofessional teamwork in an academic medical center: Near-peer
      education for students during gross medical anatomy.
AB  - The purpose of this report is to describe student satisfaction with a near-peer
      interprofessional education (IPE) session for physical therapy and medical
      students. Ten senior physical therapy students worked in peer-groups to develop a
      musculoskeletal anatomy demonstration for first-semester medical students.
      Together with their classmates, they demonstrated observation, palpation, and
      musculoskeletal assessment of the shoulder and scapular-thoracic articulation to
      medical student dissection groups in the Gross Anatomy laboratory. The medical
      students were encouraged to consider the synergistic function of shoulder
      structures and the potential impact of a selected pathology: rotator cuff injury.
      The session provided the medical students with an opportunity to integrate their
      new anatomical knowledge into a framework for clinical musculoskeletal
      evaluation. The experience offered senior physical therapy students an
      opportunity to work in teams with their peers, internalize and adapt to
      constructive feedback, and seek common ground with members of another profession.
      Both student groups reported a high degree of satisfaction with the sessions and
      expressed a desire for further interaction. These positive perceptions by student
      stakeholders have prompted us to consider additional IPE exchanges for the
      anatomy course in the upcoming school year. Given the positive outcome of this
      descriptive study, we now plan to systematically test whether near-peer IPE
      interactions can enhance the degree that students learn key anatomical concepts.

PMID- 24888729
TI  - Incidence of nutrition deterioration in nonseriously ill hospitalized children
      younger than 5 years.
AB  - BACKGROUND: The concept of deterioration of nutrition status in inpatient
      children, also called nutrition deterioration (ND), has gained widespread
      importance and is described as significant weight loss during hospitalization
      periods. Our main purpose was to determine the incidence of ND in nonseriously
      ill children younger than age 5 years admitted as inpatients and explore the
      presence of associated factors. MATERIALS AND METHODS: This descriptive study
      analyzed a prospective cohort of hospitalized children. We considered a
      significant weight loss of >2% or >0.25 SD in body mass index with respect to the
      admission weight. The correspondence between the 2 methods was assessed. The
      frequency of some clinical variables and its association with the outcome was
      explored. RESULTS: The incidence of ND was 28.5% with at least 1 of the 2 methods
      of detection and was 20% with both definitions. The correlation between both
      methods was high (kappa = 0.79). In children with ND, results were statistically
      significant in those with 5 or more stools a day, those hospitalized 5 or more
      days, and patients with lower respiratory tract disease. CONCLUSIONS: The
      incidence of ND was higher than that reported in the literature in children with
      nonserious disease. Diarrhea, lower respiratory tract disease, and hospital
      length of stay seem to be associated with these results. More studies are
      required to establish associations with those factors for an early detection of
      children at risk and for early interventions.

PMID- 24888731
TI  - Graphitic carbon nitride nanosheet-carbon nanotube three-dimensional porous
      composites as high-performance oxygen evolution electrocatalysts.
AB  - A new class of highly efficient oxygen evolution catalysts has been synthesized
      through the self-assembly of graphitic carbon nitride nanosheets and carbon
      nanotubes, driven by pi-pi stacking and electrostatic interactions. Remarkably,
      the catalysts exhibit higher catalytic oxygen evolution activity and stronger
      durability than Ir-based noble-metal catalysts and display the best performance
      among the reported nonmetal catalysts. This good result is attributed to the high
      nitrogen content and the efficient mass and charge transfer in the porous three
      dimensional nanostructure. 

PMID- 24888730
TI  - Determinants and outcomes of adherence to recommendations from a
      multidisciplinary tumour conference for hepatocellular carcinoma.
AB  - BACKGROUND: The multidisciplinary tumour conference (MTC) represents the standard
      of care in the management of hepatocellular carcinoma (HCC). Clinical outcomes in
      relation to adherence and non-adherence to MTC recommendations have not been
      studied. METHODS: A total of 137 patients with HCC and cirrhosis whose cases were
      submitted to a first MTC discussion between 1 January 2009 and 31 December 2010
      were identified. Clinical data, management recommendations, adherence, treatment
      regimens and overall survival were reviewed. RESULTS: There were 419 MTC
      discussions on 137 patients with cirrhosis and HCC. The MTC recommendations made
      in 145 discussions on 90 separate patients were not followed. Patient-related
      reasons for deviation from MTC recommendations included failure to attend for
      follow-up (n = 24, 16.6%), clinical deterioration (n = 19, 13.1%) and patient
      preference (n = 13, 9.0%). Physician-related reasons for discordance included
      treating physician preference (n = 43, 29.7%) and finding that the patient was
      not a candidate for the recommended intervention (n = 37, 25.5%). After the first
      MTC discussion, 62.0% of patients received the recommended treatment; these
      patients were more likely to be alive at 1 year compared with those who did not
      receive the recommended treatment (P = 0.007). More of the patients who followed
      recommendations underwent liver transplantation (25.6% versus 14.4%; P = 0.10).
      CONCLUSIONS: There are patient-related as well as physician-related reasons for
      non-adherence to recommendations. Non-adherence affects clinical outcomes and can
      be avoided in selected cases.

PMID- 24888732
TI  - Promoting healthy eating, active play and sustainability consciousness in early
      childhood curricula, addressing the Ben10TM problem: a randomised control trial.
AB  - BACKGROUND: This paper details the research protocol for a study funded by the
      Australian Research Council. An integrated approach towards helping young
      children respond to the significant pressures of '360 degree marketing' on their
      food choices, levels of active play, and sustainability consciousness via the
      early childhood curriculum is lacking. The overall goal of this study is to
      evaluate the efficacy of curriculum interventions that educators design when
      using a pedagogical communication strategy on children's knowledge about healthy
      eating, active play and the sustainability consequences of their toy food and toy
      selections. METHODS/DESIGN: This cluster-randomised trial will be conducted with
      300, 4 to 5 year-old children attending pre-school. Early childhood educators
      will develop a curriculum intervention using a pedagogical communication strategy
      that integrates content knowledge about healthy eating, active play and
      sustainability consciousness and deliver this to their pre-school class. Children
      will be interviewed about their knowledge of healthy eating, active play and the
      sustainability consequences of their food and toy selections. Parents will
      complete an Eating and Physical Activity Questionnaire rating their children's
      food preferences, digital media viewing and physical activity habits. All
      measures will be administered at baseline, the end of the intervention and 6
      months post intervention. Informed consent will be obtained from all parents and
      the pre-school classes will be allocated randomly to the intervention or wait
      list control group. DISCUSSION: This study is the first to utilise an integrated
      pedagogical communication strategy developed specifically for early childhood
      educators focusing on children's healthy eating, active play, and sustainability
      consciousness. The significance of the early childhood period, for young
      children's learning about healthy eating, active play and sustainability, is now
      unquestioned. The specific teaching and learning practices used by early
      childhood educators, as part of the intervention program, will incorporate a
      sociocultural perspective on learning; this perspective emphasises building on
      the play interests of children, that are experienced within the family and home
      context, as a basis for curriculum provision. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry ACTRN12614000363684: Date registered:
      07/04/2014.

PMID- 24888733
TI  - Pregnancy-associated glycoprotein (PAG) profile of Holstein-Friesian cows as
      compared to dual-purpose and beef cows.
AB  - Pregnancy-associated glycoproteins (PAGs) are produced by mono- and binucleate
      trophoblast cells in the ruminant placenta. PAG appears in maternal blood and,
      from approximately 4 weeks after fertilization onward, may serve as a reliable
      means of diagnosing pregnancy. A range of factors are said to affect plasma PAG
      concentrations, such as number and sex of foetus, mass of calf and placenta,
      level of milk production and genetic constitution. In this study, PAG pregnancy
      profiles of a dual-purpose (Simmental) and two beef breeds (Uckermark and Aubrac)
      are compared with the profile of the specialized dairy breed Holstein-Friesian.
      Holstein-Friesian cows were sampled weekly; the levels of the other breeds were
      presented at 3-week intervals. The overall significant breed difference (p =
      0.013) was founded on deviations during the initial 3 weeks of pregnancy and from
      23 weeks onward. During the period critical for the detection of pregnancy,
      between four and 22 weeks, agreement between PAG levels of various breeds was
      close (p > 0.05). No significant effect of body mass of cow or calf (relative to
      mass of dam) was detected. These findings imply that the PAG pregnancy test may
      be executed uniformly irrespective of breed or type of cow, affirming the
      suitability of the test as a valuable asset for the cattle industry.

PMID- 24888734
TI  - Protein stabilization by macromolecular crowding through enthalpy rather than
      entropy.
AB  - The interior of the cell is a densely crowded environment in which protein
      stability is affected differently than in dilute solution. Macromolecular
      crowding is commonly understood in terms of an entropic volume exclusion effect
      based on hardcore repulsions among the macromolecules. We studied the thermal
      unfolding of ubiquitin in the presence of different cosolutes (glucose, dextran,
      poly(ethylene glycol), KCl, urea). Our results show that for a correct dissection
      of the cosolute-induced changes of the free energy into its enthalpic and
      entropic contributions, the temperature dependence of the heat capacity change
      needs to be explicitly taken into account. In contrast to the prediction by the
      excluded volume theory, we observed an enthalpic stabilization and an entropic
      destabilization for glucose, dextran, and poly(ethylene glycol). The enthalpic
      stabilization mechanism induced by the macromolecular crowder dextran was similar
      to the enthalpic stabilization mechanism of its monomeric building block glucose.
      In the case of poly(ethylene glycol), entropy is dominating over enthalpy leading
      to an overall destabilization. We propose a new model to classify cosolute
      effects in terms of their enthalpic contributions to protein stability. 

PMID- 24888735
TI  - Magnetic quantum ratchet effect in Si-MOSFETs.
AB  - We report on the observation of magnetic quantum ratchet effect in metal-oxide
      semiconductor field-effect-transistors on silicon surface (Si-MOSFETs). We show
      that the excitation of an unbiased transistor by ac electric field of terahertz
      radiation at normal incidence leads to a direct electric current between the
      source and drain contacts if the transistor is subjected to an in-plane magnetic
      field. The current rises linearly with the magnetic field strength and
      quadratically with the ac electric field amplitude. It depends on the
      polarization state of the ac field and can be induced by both linearly and
      circularly polarized radiation. We present the quasi-classical and quantum
      theories of the observed effect and show that the current originates from the
      Lorentz force acting upon carriers in asymmetric inversion channels of the
      transistors.

PMID- 24888736
TI  - Using inflammatory and oxidative biomarkers in urine to predict early acute
      kidney injury in patients undergoing liver transplantation.
AB  - OBJECTIVE: We examined the value of inflammatory and oxidative biomarkers in
      predicting acute kidney injury (AKI) following orthotopic liver transplantation
      (OLT). METHODS: Urinary excretion of tumour necrosis factor-alpha (TNF-alpha),
      interleukin-8 (IL-8), interleukin-10 (IL-10), superoxide dismutase (SOD),
      malondialdehyde (MDA), 6-keto prostaglandin F1alpha (6-keto-PGF1alpha), hydrogen
      peroxide (H2O2), and 8-keto prostaglandin F2alpha (8-iso-PGF2alpha), serum
      creatinine (SCr), blood urea nitrogen (BUN), urinary N-acetyl-beta-D
      glucosaminidase (NAG), beta2-microglobulin (beta2-MG) and gamma-glutamyl
      transferase (gamma-GT), were measured before surgery (baseline), at 2 h after
      graft reperfusion and 24 h after OLT in 28 liver transplantation patients.
      RESULTS: The levels of TNF-alpha, IL-8, IL-10, SOD, MDA, 6-keto-PGF1alpha, H2O2
      and 8-iso-PGF2alpha in urine were all significantly higher in patients who had
      AKI than in those who did not at 2 h after graft reperfusion and 24 h after OLT
      (p < 0.01).

PMID- 24888737
TI  - Patterns of afferent input to the caudal and rostral areas of the dorsal premotor
      cortex (6DC and 6DR) in the marmoset monkey.
AB  - Corticocortical projections to the caudal and rostral areas of dorsal premotor
      cortex (6DC and 6DR, also known as F2 and F7) were studied in the marmoset
      monkey. Both areas received their main thalamic inputs from the ventral anterior
      and ventral lateral complexes, and received dense projections from the medial
      premotor cortex. However, there were marked differences in their connections with
      other cortical areas. While 6DR received consistent inputs from prefrontal
      cortex, area 6DC received few such connections. Conversely, 6DC, but not 6DR,
      received major projections from the primary motor and somatosensory areas.
      Projections from the anterior cingulate cortex preferentially targeted 6DC, while
      the posterior cingulate and adjacent medial wall areas preferentially targeted
      6DR. Projections from the medial parietal area PE to 6DC were particularly dense,
      while intraparietal areas (especially the putative homolog of LIP) were more
      strongly labeled after 6DR injections. Finally, 6DC and 6DR were distinct in
      terms of inputs from the ventral parietal cortex: projections to 6DR originated
      preferentially from caudal areas (PG and OPt), while 6DC received input primarily
      from rostral areas (PF and PFG). Differences in connections suggest that area 6DR
      includes rostral and caudal subdivisions, with the former also involved in
      oculomotor control. These results suggest that area 6DC is more directly involved
      in the preparation and execution of motor acts, while area 6DR integrates sensory
      and internally driven inputs for the planning of goal-directed actions. They also
      provide strong evidence of a homologous organization of the dorsal premotor
      cortex in New and Old World monkeys.

PMID- 24888738
TI  - Molecular self-assembly of arene-Ru based interlocked catenane metalla-cages.
AB  - Two interlocked trigonal prismatic metalla-cages are formed quantitatively
      through the self-assembly of pi-electron rich arene-Ru acceptors with a new
      tridentate donor. Interestingly, non-pi-electron rich arene-Ru acceptors furnish
      simple trigonal prisms when they are combined with a tridentate donor. 

PMID- 24888740
TI  - Assessment of cardiac function from fetal to adult life with myocardial
      deformation imaging.

PMID- 24888739
TI  - Hypothesis testing for an extended cox model with time-varying coefficients.
AB  - The log-rank test has been widely used to test treatment effects under the Cox
      model for censored time-to-event outcomes, though it may lose power substantially
      when the model's proportional hazards assumption does not hold. In this article,
      we consider an extended Cox model that uses B-splines or smoothing splines to
      model a time-varying treatment effect and propose score test statistics for the
      treatment effect. Our proposed new tests combine statistical evidence from both
      the magnitude and the shape of the time-varying hazard ratio function, and thus
      are omnibus and powerful against various types of alternatives. In addition, the
      new testing framework is applicable to any choice of spline basis functions,
      including B-splines, and smoothing splines. Simulation studies confirm that the
      proposed tests performed well in finite samples and were frequently more powerful
      than conventional tests alone in many settings. The new methods were applied to
      the HIVNET 012 Study, a randomized clinical trial to assess the efficacy of
      single-dose Nevirapine against mother-to-child HIV transmission conducted by the
      HIV Prevention Trial Network.

PMID- 24888741
TI  - Re: minimally invasive therapy for fetal sacrococcygeal teratoma: case series and
      systematic review of the literature. T. Van Mieghem, A. Al-Ibrahim, J. Deprest,
      L. Lewi, J. C. Langer, D. Baud, K. O'Brien, R. Beecroft, R. Chaturvedi, E.
      Jaeggi, J. Fish and G. Ryan. Ultrasound Obstet Gynecol 2014; 43: 611-619.

PMID- 24888742
TI  - Re: comparison of ultrasound and magnetic resonance imaging parameters in
      predicting survival in isolated left-sided congenital diaphragmatic hernia. M.
      Bebbington, T. Victoria, E. Danzer, J. Moldenhauer, N. Khalek, M. Johnson, H.
      Hedrick and N. S. Adzick. Ultrasound Obstet Gynecol 2014; 43: 670-674.

PMID- 24888743
TI  - Reply: To PMID 21953982.

PMID- 24888744
TI  - Caught between parasitoids and predators - survival of a specialist herbivore on
      leaves and flowers of mustard plants.
AB  - The survival of insect herbivores typically is constrained by food choice and
      predation risk. Here, we explored whether movement from leaves to flowers
      increases survival of herbivores that prefer to feed on floral tissues. Combining
      field and greenhouse experiments, we investigated whether flowering influences
      the behavior of Pieris brassicae butterflies and caterpillars and, consequently,
      herbivore survival in the field. In this context, we investigated also if flowers
      of Brassica nigra can provide caterpillars refuge from the specialist parasitoid
      Cotesia glomerata and from predatory social wasps. By moving to flowers,
      caterpillars escaped from the parasitoid. Flowers are nutritionally superior when
      compared with leaves, and caterpillars develop faster when feeding on flowers.
      However, late-stage caterpillars can be preyed upon intensively by social wasps,
      irrespective of whether they feed on leaves or flowers. We conclude that flower
      preference by P. brassicae is more likely driven by nutritional advantages and
      reduced parasitism on flowers, than by risks of being killed by generalist
      predators. 

PMID- 24888745
TI  - Nectar minerals as regulators of flower visitation in stingless bees and nectar
      hoarding wasps.
AB  - Various nectar components have a repellent effect on flower visitors, and their
      adaptive advantages for the plant are not well understood. Persea americana
      (avocado) is an example of a plant that secretes nectar with repellent
      components. It was demonstrated that the mineral constituents of this nectar,
      mainly potassium and phosphate, are concentrated enough to repel honey bees, Apis
      mellifera, a pollinator often used for commercial avocado pollination. Honey
      bees, however, are not the natural pollinator of P. americana, a plant native to
      Central America. In order to understand the role of nectar minerals in plant
      pollinator relationships, it is important to focus on the plant's interactions
      with its natural pollinators. Two species of stingless bees and one species of
      social wasp, all native to the Yucatan Peninsula, Mexico, part of the natural
      range of P. americana, were tested for their sensitivity to sugar solutions
      enriched with potassium and phosphate, and compared with the sensitivity of honey
      bees. In choice tests between control and mineral-enriched solutions, all three
      native species were indifferent for mineral concentrations lower than those
      naturally occurring in P. americana nectar. Repellence was expressed at
      concentrations near or exceeding natural concentrations. The threshold point at
      which native pollinators showed repellence to increasing levels of minerals was
      higher than that detected for honey bees. The results do not support the
      hypothesis that high mineral content is attractive for native Hymenopteran
      pollinators; nevertheless, nectar mineral composition may still have a role in
      regulating flower visitors through different levels of repellency. 

PMID- 24888746
TI  - Combined effects of CO2 enrichment, diurnal light levels and water stress on
      foliar metabolites of potato plants grown in naturally sunlit controlled
      environment chambers.
AB  - Experiments were conducted in outdoor, naturally sunlit, soil-plant-atmosphere
      research (SPAR) chambers using plants grown in pots. Drought treatments were
      imposed on potato plants (Solanum tuberosum cv. Kennebec) beginning 10 days after
      tuber initiation. A total of 23 out of 37 foliar metabolites were affected by
      drought when measured 11 days after initiating water stress treatments. Compounds
      that accumulated in response to drought were hexoses, polyols, branched chain
      amino acids (BCAAs) and aromatic amino acids, such as proline. Conversely, leaf
      starch, alanine, aspartate and several organic acids involved in respiratory
      metabolism decreased with drought. Depending upon harvest date, a maximum of 12
      and 17 foliar metabolites also responded to either CO2 enrichment or diurnal
      treatments, respectively. In addition, about 20% of the measured metabolites in
      potato leaflets were simultaneously affected by drought, CO2 enrichment and
      diurnal factors combined. This group contained BCAAs, hexoses, leaf starch and
      malate. Polyols and proline accumulated in response to water stress but did not
      vary diurnally. Water stress also amplified diurnal variations of hexoses and
      starch in comparison to control samples. Consequently, specific drought
      responsive metabolites in potato leaflets were dramatically affected by daily
      changes of photosynthetic carbon metabolism. 

PMID- 24888747
TI  - Magnetocaloric effects in a freestanding and flexible graphene-based superlattice
      synthesized with a spatially confined reaction.
AB  - Superlattices have attracted great interest because of their tailorable
      electronic properties at the interface. However, the lack of an efficient and low
      cost synthetic method represents a huge challenge to implement superlattices into
      practical applications. Herein, we report a space-confined nanoreactor strategy
      to synthesize flexible freestanding graphene-based superlattice nanosheets, which
      consist of alternately intercalated monolayered metal-oxide frameworks and
      graphene. Taking vanadium oxide as an example, clear-cut evidences in extended X
      ray absorption fine structure, high-resolution transmission electron microscopy
      and infrared spectra have confirmed that the vanadium oxide frameworks in the
      superlattice nanosheets show high symmetry derived from the space-confinement and
      electron-donor effect of graphene layers, which enable the superlattice
      nanosheets to show emerging magnetocaloric effect. Undoubtedly, this freestanding
      and flexible superlattice synthesized from a low-cost and scalable method avoids
      complex transferring processes from growth substrates for final applications and
      thus should be beneficial to a wide variety of functionalized devices. 

PMID- 24888748
TI  - The moral code in Islam and organ donation in Western countries: reinterpreting
      religious scriptures to meet utilitarian medical objectives.
AB  - End-of-life organ donation is controversial in Islam. The controversy stems from:
      (1) scientifically flawed medical criteria of death determination; (2) invasive
      perimortem procedures for preserving transplantable organs; and (3) incomplete
      disclosure of information to consenting donors and families. Data from a survey
      of Muslims residing in Western countries have shown that the interpretation of
      religious scriptures and advice of faith leaders were major barriers to
      willingness for organ donation. Transplant advocates have proposed corrective
      interventions: (1) reinterpreting religious scriptures, (2) reeducating faith
      leaders, and (3) utilizing media campaigns to overcome religious barriers in
      Muslim communities. This proposal disregards the intensifying scientific, legal,
      and ethical controversies in Western societies about the medical criteria of
      death determination in donors. It would also violate the dignity and
      inviolability of human life which are pertinent values incorporated in the
      Islamic moral code. Reinterpreting religious scriptures to serve the utilitarian
      objectives of a controversial end-of-life practice, perceived to be socially
      desirable, transgresses the Islamic moral code. It may also have deleterious
      practical consequences, as donors can suffer harm before death. The negative
      normative consequences of utilitarian secular moral reasoning reset the Islamic
      moral code upholding the sanctity and dignity of human life. 

PMID- 24888749
TI  - Dialysis access venous stenosis: treatment with balloon angioplasty 30-second vs.
      1-minute inflation times.
AB  - Percutaneous balloon angioplasty is the standard of care in the endovascular
      treatment of dialysis access venous stenosis. The significance of balloon
      inflation times in the treatment of these stenoses is not well defined. Our
      objective was to examine the outcomes of 30-second vs. 1-minute balloon inflation
      times on primary-assisted patency of arteriovenous fistulae and grafts. Using a
      prospectively collected vascular access database, we identified a total of 75
      patients referred for access dysfunction during a 5-year period. These patients
      received 223 interventions (178 with 30-second inflations and 45 with 1-minute
      inflations). We compared primary-assisted patency during the subsequent 9 months
      across groups defined by inflation times. Demographics and baseline
      characteristics were similar across groups. Immediate technical success and
      patency in the first 3 months were similar across groups (hazard ratio [HR] =
      0.86; 95% confidence interval [CI]: 0.34-2.20). After 3 months, however, a 1
      minute inflation time was associated with greater incidence of access failure
      (adjusted HR [aHR] = 1.74; 95% CI: 1.09-2.79). Other predictors of access failure
      included age over 60 (aHR = 1.02; 95% CI: 1.01-1.04), central location of the
      lesion (aHR = 2.49; CI: 1.27-4.89), and three or more prior procedures (aHR 2.48;
      CI: 1.19-5.16). Our data suggest that shorter balloon inflation times may be
      associated with improved longer term access patency, although the benefit was not
      observed until after 3 months. Given the increasing demands of maintaining access
      patency in the era of the National Kidney Foundation Kidney Disease Outcomes
      Quality Initiative and Fistula First, the role of angioplasty times requires
      further study. 

PMID- 24888750
TI  - Pathological Internet use among European adolescents: psychopathology and self
      destructive behaviours.
AB  - Rising global rates of pathological Internet use (PIU) and related psychological
      impairments have gained considerable attention in recent years. In an effort to
      acquire evidence-based knowledge of this relationship, the main objective of this
      study was to investigate the association between PIU, psychopathology and self
      destructive behaviours among school-based adolescents in eleven European
      countries. This cross-sectional study was implemented within the framework of the
      European Union project: Saving and Empowering Young Lives in Europe. A
      representative sample of 11,356 school-based adolescents (M/F: 4,856/6,500; mean
      age: 14.9) was included in the analyses. PIU was assessed using the Young's
      Diagnostic Questionnaire. Psychopathology was measured using the Beck Depression
      Inventory-II, Zung Self-Rating Anxiety Scale and Strengths and Difficulties
      Questionnaire. Self-destructive behaviours were evaluated by the Deliberate Self
      Harm Inventory and Paykel Suicide Scale. Results showed that suicidal behaviours
      (suicidal ideation and suicide attempts), depression, anxiety, conduct problems
      and hyperactivity/inattention were significant and independent predictors of PIU.
      The correlation between PIU, conduct problems and hyperactivity/inattention was
      stronger among females, while the link between PIU and symptoms of depression,
      anxiety and peer relationship problems was stronger among males. The association
      between PIU, psychopathology and self-destructive behaviours was stronger in
      countries with a higher prevalence of PIU and suicide rates. These findings
      ascertain that psychopathology and suicidal behaviours are strongly related to
      PIU. This association is significantly influenced by gender and country
      suggesting socio-cultural influences. At the clinical and public health levels,
      targeting PIU among adolescents in the early stages could potentially lead to
      improvements of psychological well-being and a reduction of suicidal behaviours. 

PMID- 24888751
TI  - Trends in psychopharmacologic treatment of tic disorders in children and
      adolescents in Germany.
AB  - Data on medical treatment of children and adolescents with tic disorders are
      scarce. This study examined the administrative prevalence of
      psychopharmacological prescriptions in this patient group in Germany. Data of the
      largest German health insurance fund were analysed. In outpatients aged 0-19
      years with diagnosed tic disorder, psychotropic prescriptions were evaluated for
      the years 2006 and 2011. In 2011, the percentage of psychotropic prescriptions
      was slightly higher than in 2006 (21.2 vs. 18.6%). The highest prescription
      prevalence was found in Tourette syndrome (51.5 and 53.0%, respectively). ADHD
      drugs were most frequently prescribed, followed by antipsychotics. In 2011,
      prescriptions of second generation antipsychotics (SGA) were higher and
      prescriptions of first generation antipsychotics (FGA) lower than in 2006.
      Concerning prescribed antipsychotic substances, in 2011 risperidone prescriptions
      were higher and tiapride prescriptions lower. Paediatricians issued 37.4%, and
      child and adolescent psychiatrists issued 37.1% of psychotropic prescriptions.
      The FGA/SGA ratio was highest in GPs (1.25) and lowest in child and adolescent
      psychiatrists (0.96). From 2006 to 2011, there was only a slight increase in
      psychotropic prescriptions for children and adolescents with a diagnosis of tic
      disorder in Germany, which stands in contrast towards the significant increase in
      psychotropic prescriptions in other child and adolescent psychiatric disorders
      (e.g. ADHD). There were marked differences in treatment patterns by tic disorder
      subgroups, with Tourette syndrome patients receiving most frequently
      psychopharmacotherapy. Risperidone prescriptions increased, probably reflecting a
      switch in prescribing practice towards up-to-date treatment guidelines. In
      primary care physicians, dissemination of current tic disorder treatment
      guidelines might constitute an important educational goal.

PMID- 24888752
TI  - Genome-wide analysis of the distribution of AP2/ERF transcription factors reveals
      duplication and CBFs genes elucidate their potential function in Brassica
      oleracea.
AB  - BACKGROUND: Cabbage (Brassica oleracea) is one of the most important leaf
      vegetables grown worldwide. The entire cabbage genome sequence and more than
      fifty thousand proteins have been obtained to date. However a high degree of
      sequence similarity and conserved genome structure remain between cabbage and
      Arabidopsis; therefore, Arabidopsis is a viable reference species for comparative
      genomics studies. Transcription factors (TFs) are important regulators involved
      in plant development and physiological processes and the AP2/ERF protein family
      contains transcriptional factors that play a crucial role in plant growth and
      development, as well as response to biotic and abiotic stress conditions in
      plants. However, no detailed expression profile of AP2/ERF-like genes is
      available for B. oleracea. RESULTS: In the present study, 226 AP2/ERF TFs were
      identified from B. oleracea based on the available genome sequence. Based on
      sequence similarity, the AP2/ERF superfamily was classified into five groups
      (DREB, ERF, AP2, RAV and Soloist) and 15 subgroups. The identification,
      classification, phylogenetic construction, conserved motifs, chromosome
      distribution, functional annotation, expression patterns and interaction network
      were then predicted and analyzed. AP2/ERF transcription factor expression levels
      exhibited differences in response to varying abiotic stresses based on expressed
      sequence tags (ESTs). BoCBF1a, 1b, 2, 3 and 4, which were highly conserved in
      Arabidopsis and B. rapa CBF/DREB genes families were well characterized.
      Expression analysis enabled elucidation of the molecular and genetic level
      expression patterns of cold tolerance (CT) and susceptible lines (CS) of cabbage
      and indicated that all BoCBF genes responded to abiotic stresses. CONCLUSIONS:
      Comprehensive analysis of the physiological functions and biological roles of
      AP2/ERF superfamily genes and BoCBF family genes in B. oleracea is required to
      fully elucidate AP2/ERF, which will provide rich resources and opportunities to
      understand abiotic stress tolerance in crops.

PMID- 24888753
TI  - Clinical outcome of subcentimeter non-small cell lung cancer after surgical
      resection: single institution experience of 105 patients.
AB  - BACKGROUND: The detection of subcentimeter lung cancers has significantly
      improved with advances in computed tomography and the emergence of screening
      protocols. We reviewed the clinicopathological features and surgical outcomes of
      patients with subcentimeter non-small cell lung cancer (NSCLC) in our
      institution. METHODS: A total of 105 patients who underwent lobectomy or sublobar
      resection for subcentimeter NSCLCs were retrospectively reviewed.
      Clinicopathological characteristics and survival were analyzed statistically
      using Student's t-test for continuous variables, Fisher's exact for categorical
      variables and Cox regression for multivariable analysis. RESULTS: A total of 105
      patients (35 male, 70 female; mean age 61.4, range 38-77 years) were analyzed.
      Patients underwent lobectomy (n = 71), segmentectomy (n = 19), or wedge resection
      (n = 15). The overall 5-year survival was 91.3%. No significant differences were
      observed in overall and recurrence-free survival after segmentectomy or
      lobectomy; patients undergoing wedge resection had shorter survival compared to
      those who underwent lobectomy. Elevated preoperative serum CEA levels and
      positive nodal status correlated with poorer survival, and were identified as
      independent prognostic factors in multivariate analysis. CONCLUSION: Systematic
      nodal dissection is recommended for patients with subcentimeter NSCLC.
      Segmentectomy offers comparable oncologic results to lobectomy. Elevated
      preoperative serum CEA level implies shorter survival for patients with these
      tiny tumors.

PMID- 24888754
TI  - Visual motion shifts saccade targets.
AB  - Saccades are made thousands of times a day and are the principal means of
      localizing objects in our environment. However, the saccade system faces the
      challenge of accurately localizing objects as they are constantly moving relative
      to the eye and head. Any delays in processing could cause errors in saccadic
      localization. To compensate for these delays, the saccade system might use one or
      more sources of information to predict future target locations, including changes
      in position of the object over time, or its motion. Another possibility is that
      motion influences the represented position of the object for saccadic targeting,
      without requiring an actual change in target position. We tested whether the
      saccade system can use motion-induced position shifts to update the represented
      spatial location of a saccade target, by using static drifting Gabor patches with
      either a soft or a hard aperture as saccade targets. In both conditions, the
      aperture always remained at a fixed retinal location. The soft aperture Gabor
      patch resulted in an illusory position shift, whereas the hard aperture stimulus
      maintained the motion signals but resulted in a smaller illusory position shift.
      Thus, motion energy and target location were equated, but a position shift was
      generated in only one condition. We measured saccadic localization of these
      targets and found that saccades were indeed shifted, but only with a soft
      aperture Gabor patch. Our results suggest that motion shifts the programmed
      locations of saccade targets, and this remapped location guides saccadic
      localization. 

PMID- 24888755
TI  - Manipulations to reduce simulator-related transient adverse health effects during
      simulated driving.
AB  - User comfort during simulated driving is of key importance, since reduced comfort
      can confound the experiment and increase dropout rates. A common comfort
      affecting factor is simulator-related transient adverse health effect (SHE). In
      this study, we propose and evaluate methods to adapt a virtual driving scene to
      reduce SHEs. In contrast to the manufacturer-provided high-sensory conflict scene
      (high-SCS), we developed a low-sensory conflict scene (low-SCS). Twenty young,
      healthy participants drove in both the high-SCS and the low-SCS scene for 10 min
      on two different days (same time of day, randomized order). Before and after
      driving, participants rated SHEs by completing the Simulator Sickness
      Questionnaire (SSQ). During driving, several physiological parameters were
      recorded. After driving in the high-SCS, the SSQ score increased in average by
      129.4 (122.9 %, p = 0.002) compared to an increase of 5.0 (3.4 %, p = 0.878)
      after driving in the low-SCS. In the low-SCS, skin conductance decreased by 13.8
      % (p < 0.01) and saccade amplitudes increased by 16.1 % (p < 0.01). Results show
      that the investigated methods reduce SHEs in a younger population, and the low
      SCS is well accepted by the users. We expect that these measures will improve
      user comfort.

PMID- 24888757
TI  - Visible-light-induced direct C(sp3)-H difluromethylation of
      tetrahydroisoquinolines with the in situ generated difluoroenolates.
AB  - An effective approach to C1-difluoromethylated tetrahydroisoquinoline derivatives
      has been developed through C-H functionalization of tertiary amines by visible
      light photoredox catalysis. This method uses stable, easily obtained alpha,alpha
      difluorinated gem-diol as the CF2 source. The corresponding products were
      obtained in moderate to high yields at ambient temperature. 

PMID- 24888756
TI  - A nonlinear finite element simulation of balloon expandable stent for assessment
      of plaque vulnerability inside a stenotic artery.
AB  - The stresses induced on plaque wall during stent implantation inside a stenotic
      artery are associated with plaque rupture. The stresses in the plaque-artery
      stent structure appear to be distinctly different for different plaque types in
      terms of both distribution and magnitude. In this study, a nonlinear finite
      element simulation was executed to analyze the influence of plaque composition
      (calcified, cellular, and hypocellular) on plaque, artery layers (intima, media,
      and adventitia), and stent stresses during implantation of a balloon expandable
      coronary stent into a stenosed artery. The atherosclerotic artery was assumed to
      consist of a plaque and normal arterial tissues on its outer side. The results
      revealed a significant influence of plaque types on the maximum stresses induced
      within plaque wall and artery layers during stenting, but not when calculating
      maximum stress on stent. The stress on stiffer calcified plaque wall was in the
      fracture level (2.21 MPa), whereas cellular and hypocellular plaques play a
      protective role by displaying less stress on their wall. The highest von Mises
      stresses were observed on less stiff media layer. The findings of this study
      suggest a lower risk of arterial vascular injury for calcified plaque, while
      higher risk of plaque ruptures for cellular and hypocellular plaques.

PMID- 24888758
TI  - Azaphosphatrane organocatalysts in confined space: cage effect in CO(2)
      conversion.
AB  - The endohedral functionalization of a molecular cage by an azaphosphatrane unit
      has allowed for the creation of highly engineered catalytic cavities for
      efficient conversion of CO2 into cyclic carbonates. Strong
      structure/activity/stability correlations have been demonstrated by careful
      adjustment of the size, shape, and electronic properties of the hemicryptophane
      host. 

PMID- 24888761
TI  - Photoconversion of 6,13-alpha-diketopentacene in the crystalline phase.
AB  - The photoconversion of a crystalline-phase precursor, 6,13-dihydro-6,13
      ethanopentacene-15,16-dione (PDK), into pentacene was examined. Upon irradiation
      with 470 nm light, the photoconversion proceeded even in the crystalline phase.
      Although the rate of the crystalline phase photoconversion was much slower than
      that in solution, quantitative photoconversion was achieved upon lengthy
      photoirradiation. The photoconversion of PDK was also confirmed at the single MUm
      sized crystal level by observing fluorescence images and spectra of the PDK
      crystal using confocal microscopy. Destruction of the crystal was observed when
      some of the PDK molecules in the crystal were photoconverted into pentacene.
      These results indicate that the crystalline-phase photoconversion of PDK
      proceeded through the destruction of the crystal. Quantitative photoconversion
      was achieved as a result. 

PMID- 24888760
TI  - Heterochrony in mandible development of larval shrimp (Decapoda: Caridea)--a
      comparative morphological SEM study of two carideans.
AB  - Mandible development in the larval stages I-V of two palaemonid shrimp species,
      Palaemon elegans and Macrobrachium amazonicum, was analyzed using scanning
      electron microscopy, light microscopy, and confocal laser scanning microscopy. In
      contrast to the zoea I of P. elegans, first-stage larvae of M. amazonicum are
      nonfeeding. At hatching, the morphology of the mandibles is fully expressed in P.
      elegans, while it appears underdeveloped in M. amazonicum, presenting only small
      precursors of typical caridean features. In successive zoeal stages, both species
      show similar developmental changes, but the mandibular characters of the larvae
      in M. amazonicum were delayed compared to the equivalent stages in P. elegans,
      especially in the development of submarginal setae and mandible size. In
      conclusion, our results indicate heterochrony (postdisplacement) of mandible
      development in M. amazonicum compared to that in P. elegans, which is related to
      initial lack of mandible functionality or planktivorous feeding at hatching,
      respectively. This conclusion is supported by comparison with other palaemonid
      zoeae exhibiting different feeding modes. Our data suggest that an evolutionary
      ground pattern of mandible morphology is present even in species with nonfeeding
      first-stage larvae.

PMID- 24888759
TI  - Penthrox inhaler analgesia in transrectal ultrasound-guided prostate biopsy.
AB  - BACKGROUND: Periprostatic injection of local anaesthetic (PILA) has been shown to
      significantly reduce pain in patients undergoing transrectal ultrasound-guided
      prostate biopsy (TRUSPB). However, this method does not address pain that is
      associated with ultrasound probe insertion, and the injection of local
      anaesthetic itself causes pain. The aim of this study was to explore the efficacy
      of methoxyflurane delivered by a Penthrox inhaler as a novel method of pain
      relief during TRUSPB. METHOD: From July 2012 to July 2013, 64 patients were
      scheduled at a single centre to undergo TRUSPB while receiving analgesia via
      Penthrox inhaler. Fifteen minutes after the biopsy procedure, these patients were
      asked to complete a pain score survey using a 10-cm visual analogue scale (VAS)
      to separately report the degree of pain experienced during digital rectal
      examination (DRE), ultrasound probe insertion and core biopsy. RESULTS: The
      median pain scores on a 10-cm VAS were 2.0, 2.4 and 3.0 during DRE, probe
      insertion and needle biopsy, respectively, while using the Penthrox inhaler. Of
      the 64 patients, 11 had undergone TRUSPB previously receiving PILA. In these
      patients, PILA was significantly better than the Penthrox inhaler for pain relief
      during needle biopsy (median pain score 2.0 versus 4.0; P = 0.012). CONCLUSION:
      The Penthrox inhaler appears to be a safe and effective method of analgesia for
      TRUSPB. Patients who had experienced both PILA and Penthrox reported pain scores
      that significantly favoured PILA over the Penthrox inhaler.

PMID- 24888762
TI  - Expression and evaluation of enzymes required for the hydrolysis of
      galactomannan.
AB  - The cost-effective production of bioethanol from lignocellulose requires the
      complete conversion of plant biomass, which contains up to 30 % mannan. To ensure
      utilisation of galactomannan during consolidated bioprocessing, heterologous
      production of mannan-degrading enzymes in fungal hosts was explored. The
      Aspergillus aculeatus endo-beta-mannanase (Man1) and Talaromyces emersonii alpha
      galactosidase (Agal) genes were expressed in Saccharomyces cerevisiae Y294, and
      the Aspergillus niger beta-mannosidase (cMndA) and synthetic Cellvibrio mixtus
      beta-mannosidase (Man5A) genes in A. niger. Maximum enzyme activity for Man1 (374
      nkat ml(-1), pH 5.47), Agal (135 nkat ml(-1), pH 2.37), cMndA (12 nkat ml(-1), pH
      3.40) and Man5A (8 nkat ml(-1), pH 3.40) was observed between 60 and 70  degrees
      C. Co-expression of the Man1 and Agal genes in S. cerevisiae Y294[Agal-Man1]
      reduced the extracellular activity relative to individual expression of the
      respective genes. However, the combined action of crude Man1, Agal and Man5A
      enzyme preparations significantly decreased the viscosity of galactomannan in
      locust bean gum, confirming hydrolysis thereof. Furthermore, when complemented
      with exogenous Man5A, S. cerevisiae Y294[Agal-Man1] produced 56 % of the
      theoretical ethanol yield, corresponding to a 66 % carbohydrate conversion, on 5
      g l(-1) mannose and 10 g l(-1) locust bean gum.

PMID- 24888763
TI  - The effect of duty hour regulations on outcomes of neurological surgery in
      training hospitals in the United States: duty hour regulations and patient
      outcomes.
AB  - OBJECT: The effects of sleep deprivation on performance have been well documented
      and have led to changes in duty hour regulation. New York State implemented
      stricter duty hours in 1989 after sleep deprivation among residents was thought
      to have contributed to a patient's death. The goal of this study was to determine
      if increased regulation of resident duty hours results in measurable changes in
      patient outcomes. METHODS: Using the Nationwide Inpatient Sample (NIS), patients
      undergoing neurosurgical procedures at hospitals with neurosurgery training
      programs were identified and screened for in-hospital complications, in-hospital
      procedures, discharge disposition, and in-hospital mortality. Comparisons in the
      above outcomes were made between New York hospitals and non-New York hospitals
      before and after the Accreditation Council for Graduate Medical Education (ACGME)
      regulations were put into effect in 2003. RESULTS: Analysis of discharge
      disposition demonstrated that 81.9% of patients in the New York group 2000-2002
      were discharged to home compared with 84.1% in the non-New York group 2000-2002
      (p = 0.6, adjusted multivariate analysis). In-hospital mortality did not
      significantly differ (p = 0.7). After the regulations were implemented, there was
      a nonsignificant decrease in patients discharged to home in the non-New York
      group: 84.1% of patients in the 2000-2002 group compared with 81.5% in the 2004
      2006 group (p = 0.6). In-hospital mortality did not significantly change (p =
      0.9). In New York there was no significant change in patient outcomes with the
      implementation of the regulations; 81.9% of patients in the 2000-2002 group were
      discharged to home compared with 78.0% in the 2004-2006 group (p = 0.3). In
      hospital mortality did not significantly change (p = 0.4). After the regulations
      were in place, analysis of discharge disposition demonstrated that 81.5% of
      patients in the non-New York group 2004-2006 were discharged to home compared
      with 78.0% in the New York group 2004-2006 (p = 0.01). In-hospital mortality was
      not significantly different (p = 0.3). CONCLUSIONS: Regulation of resident duty
      hours has not resulted in significant changes in outcomes among neurosurgical
      patients.

PMID- 24888764
TI  - Involvement of RBP4 in hyperinsulinism-induced vascular smooth muscle cell
      proliferation.
AB  - Retinol-binding protein 4 (RBP4) is a newly discovered adipocytokine related to
      insulin resistance (IR). Hyperinsulinemia and IR are the major risk factors for
      cardiovascular diseases (CVD). The role of RBP4 in CVD has not yet been
      determined. The present study was designed to analyze the correlation of RBP4 and
      CVD risk factors and to evaluate the role of RBP4 in proliferation of vascular
      smooth muscle cells during hyperinsulinemia and the underlying mechanisms. Plasma
      RBP4 concentration, IR-related indexes, and cardiovascular risk factors were
      measured from blood samples of hyperinsulinemic rats (HIns) and control SD rats
      (Cons). The vascular morphology and the expression of ERK1/2, p-ERK1/2 in
      arterial tissues of rats were assessed. Different concentrations of RBP4 (1, 4
      MUg/ml) were used as intervention factor during insulin-induced aortic smooth
      muscle cells (RASMCs) proliferation. The expression of cell growth signaling
      pathways was assessed to identify the active pathway during this proliferation.
      Specifically, ERK1/2 inhibitor PD98059 and JAK2 inhibitor AG490 were used to
      detect it. RBP4 expression was higher in HIns compared with Cons (p < 0.01).
      Plasma RBP4 concentrations were positively correlated with TG (r = 0.490), hsCRP
      (r = 0.565), media thickness (r = 0.890), and p-ERK1/2 protein (r = 0.746) (p <
      0.05 each). In cultured RASMCs, RBP4 enhanced insulin-induced proliferation of
      cells and expression of p-ERK1/2 and p-JAK2. Blockade of ERK1/2 signaling pathway
      inhibited RBP4-induced proliferation of RASMCs, while suppressing JAK2 remains
      unchanged. These results suggest that plasma RBP4 concentrations were associated
      with CVD. In addition, RBP4 increases the proliferation of VSMCs induced by
      hyperinsulinism via activation of MAPK signaling pathway.

PMID- 24888765
TI  - The treatment of hyperprolactinemia in postmenopausal women with prolactin
      secreting microadenomas: cons.

PMID- 24888766
TI  - Production of natural antimicrobial compound D-phenyllactic acid using
      Leuconostoc mesenteroides ATCC 8293 whole cells involving highly active D-lactate
      dehydrogenase.
AB  - Phenyllactic acid (PLA) is an antimicrobial compound naturally synthesized in
      various fermented foods and its D-form of PLA is known to be more active than the
      L-isomer. In this study, Leuconostoc mesenteroides ATCC 8293 cells, elaborating D
      lactate dehydrogenase (D-ldh) were used to produce D-PLA from phenylpyruvic acid
      (PPA). When cultured in the presence of PPA (<=50 mmol l(-1)), growing cells
      produced a maximum yield of 35 mmol l(-1) of D-PLA, and the yields were between
      75.2 and 83.3%. Higher conversion yields were obtained at pH 6.0-7.0 when growing
      cells were used, while the optimum pH range was broader for resting cells. The
      time required for the complete conversion of PPA into PLA could be shortened to 3
      h using resting cells. D-ldh, an enzyme encoded by the LEUM_1756 gene of Leuc.
      mesenteroides ATCC 8293, was found to be responsible for the conversion of PPA
      into PLA. The Km and kcat values of the enzyme for PPA were found to be 15.4 mmol
      l(-1) and 5645 s(-1), respectively. The conditions required for the efficient
      production of D-PLA were optimized for both growing and resting cells of Leuc.
      mesenteroides, with special emphasis on achieving high stereoselectivity and
      conversion yield. Significance and impact of the study: This is the first study
      on the production of D-phenyllactic acid, which is a natural antimicrobial
      compound, from phenylpyruvate using Leuconostoc mesenteroides cells. The strain,
      ATCC 8293, that was used in the study, possesses high stereoselectivity and
      delivers a high yield. Therefore, it might be a promising candidate for use in
      large-scale production facilities and in fermented foods.

PMID- 24888767
TI  - Enhanced detection for determination of enantiomeric purity of novel agomelatine
      analogs by EKC using single and dual cyclodextrin systems.
AB  - Performing CD-EKC, baseline separation of five agomelatine analogs, potential
      antidepressant compounds, was achieved. A method for the enantioresolution and
      determination of enantiomeric purity of these naphthalene derivatives was
      developed using capillaries dynamically coated with polyethylene oxide and
      anionic cyclodextrins (highly sulfated CD) as chiral selectors. Operational
      parameters such as the nature and concentration of the cyclodextrins were
      investigated. In a second step the implementation of a dual cyclodextrin system
      was found to strongly enhance the LOD of the analytes. After optimization, best
      conditions were a 25 mM phosphate buffer at pH 2.5 containing 5% w/v (i.e. 19.7
      mM) of highly sulfated-gamma-CD and 10 mM of 6-monodeoxy-6-monoamino-beta-CD dual
      system, leading to resolution of, at least, 3.6 in 35 min. A preliminary
      validation of the developed method was undertaken: linearity, precision, and LOD
      and LOQ were evaluated. The latest ones were found equal to 0.25 and 0.82 MUM and
      to 0.31 and 0.96 MUM respectively for the first and the second enantiomer of
      compound 1. 

PMID- 24888768
TI  - Assessment of the Triggerfish contact lens sensor for measurement of intraocular
      pressure variations.

PMID- 24888770
TI  - Trigeminal autonomic cephalalgias.
AB  - The trigeminal autonomic cephalalgias (TACs) are a group of primary headache
      disorders characterised by lateralized symptoms: prominent headache and
      ipsilateral cranial autonomic features, such as conjunctival injection,
      lacrimation and rhinorrhea. The TACs are: cluster headache (CH), paroxysmal
      hemicrania (PH), short-lasting unilateral neuralgiform headache attacks with
      conjunctival injection and tearing (SUNCT)/short-lasting neuralgiform headache
      attacks with cranial autonomic features (SUNA) and hemicrania continua (HC).
      Their diagnostic criteria are outlined in the International Classification of
      Headache Disorders, third edition-beta (ICHD-IIIb). These conditions are
      distinguished by their attack duration and frequency, as well as response to
      treatment. HC is continuous and by definition responsive to indomethacin. The
      main differential when considering this headache is chronic migraine. Other TACs
      are remarkable for their short duration and must be distinguished from other
      short-lasting painful conditions, such as trigeminal neuralgia and primary
      stabbing headache. Cluster headache is characterised by exquisitely painful
      attacks that occur in discrete episodes lasting 15-180 min a few times a day. In
      comparison, PH occurs more frequently and is of shorter duration, and like HC is
      responsive to indomethacin. SUNCT/SUNA is the shortest duration and highest
      frequency TAC; attacks can occur over a hundred times every day. 

PMID- 24888769
TI  - The structure of a far-red fluorescent protein, AQ143, shows evidence in support
      of reported red-shifting chromophore interactions.
AB  - Engineering fluorescent proteins (FPs) to emit light at longer wavelengths is a
      significant focus in the development of the next generation of fluorescent
      biomarkers, as far-red light penetrates tissue with minimal absorption, allowing
      better imaging inside of biological hosts. Structure-guided design and directed
      evolution have led to the discovery of red FPs with significant bathochromic
      shifts to their emission. Here, we present the crystal structure of one of the
      most bathochromically shifted FPs reported to date, AQ143, a nine-point mutant of
      aeCP597, a chromoprotein from Actinia equina. The 2.19 A resolution structure
      reveals several important chromophore interactions that contribute to the
      protein's far-red emission and shows dual occupancy of the green and red
      chromophores. 

PMID- 24888771
TI  - Association between ablation technology and asymptomatic cerebral injury
      following atrial fibrillation ablation.
AB  - BACKGROUND: Asymptomatic cerebral injury (ACI) detected by diffusion-weighted
      magnetic resonance imaging (MRI) following atrial fibrillation (AF) ablation has
      been reported recently. The purpose of this study was to provide an overview of
      the incidence of ACI detected by MRI following AF ablation and to explore the
      association between ablation technology and ACI by systematically reviewing
      published trials. METHODS AND RESULTS: PubMed, Web of Science, and the Cochrane
      Library Databases were systematically searched for studies exploring ACI detected
      by MRI following AF ablation. Incidence of ACI, odds ratios, and 95% confidence
      intervals (CIs) were pooled. We identified 21 eligible studies. The combined ACI
      incidence across all studies was 15.9% (95% CI: 0.124-0.202). We also did a
      subgroup analysis stratified by different technologies. The incidence of ACI
      stratified by ablation technology was 13.0%, 27.6%, 12.5%, 17.3%, and 32.6% of
      the irrigated radiofrequency (RF), multielectrode-phased RF pulmonary vein
      ablation catheter (PVAC), cryoballoon, laser balloon, and nMARQTM groups,
      respectively. CONCLUSIONS: The incidence of ACI following AF ablation with PVAC
      was higher than with other technologies. Uninterrupted oral anticoagulant (OAC)
      during the procedure could lower the incidence of ACI. It seems prudent not to
      interrupt OACs during the procedure. In addition, intraprocedural activated
      clotting time was associated with ACI. Different MRI diagnostic criteria for ACI
      also influenced the results. To facilitate the future research, a generally
      accepted definition for silent cerebrovascular ischemia suitable to different
      kinds of MRI is needed.

PMID- 24888773
TI  - Mice lacking alpha1,3-fucosyltransferase 9 exhibit modulation of in vivo immune
      responses against pathogens.
AB  - Carbohydrate structures, including Lewis X (Le(x)), which is not synthesized in
      mutant mice that lack alpha1,3-fucosyltransferase 9 (Fut9(-/-)), are involved in
      cell-cell recognition and inflammation. However, immunological alteration in
      Fut9(-/-) mice has not been studied. Thus, the inflammatory response of Fut9(-/-)
      mice was examined using the highly neurovirulent mouse hepatitis virus (MHV) JHMV
      srr7 strain. Pathological study revealed that inflammation induced in the brains
      of Fut9(-/-) mice after infection was more extensive compared with that of wild
      type mice, although viral titers obtained from the brains of mutant mice were
      lower than those of wild-type mice. Furthermore, the reduction in cell numbers in
      the spleens of wild-type mice after infection was not observed in the infected
      Fut9(-/-) mice. Although there were no clear differences in the levels of
      cytokines examined in the brains between Fut9(-/-) and wild-type mice except for
      interferon-beta expression, some of those in the spleens, including interferon
      gamma, interleukin-6, and monocyte chemoattractant protein 1, showed higher
      levels in Fut9(-/-) than in wild-type mice. Furthermore, Fut9(-/-) mice were
      refractory to the in vivo inoculation of endotoxin (LPS) compared with wild-type
      mice. These results indicate that Le(x) structures are involved in host responses
      against viral or bacterial challenges.

PMID- 24888774
TI  - Optimal fixation for total preanalytic phase evaluation in pathology
      laboratories: a comprehensive study including immunohistochemistry, DNA, and mRNA
      assays.
AB  - The purpose of this study was to set the optimal preanalytical fixation protocol
      to enhance analytical and postanalytical phase accuracy and consistency. Twenty
      five normal colorectal tissues were fixed using various formalin concentrations,
      pHs, and fixation periods. All specimens were embedded in paraffin and 4 MUm
      sections were used for immunohistochemistry of Ki-67, and extraction and
      amplification of DNA and RNA. The Ki-67 labeling index and the successful gene
      amplification rate for DNA and mRNA were evaluated and compared among variously
      fixed tissue samples. Ki-67 positivity was enhanced by low pH and short fixation
      time, and was influenced by the type of antibody, but not by the staining (with
      or without using an autostainer) method. DNA amplification by PCR was strongly
      influenced by pH of formalin. cDNA amplification could be accomplished only with
      the shortest PCR fragment of 142 bp, and longer fixation times impaired the
      amplification. These data suggest that multiple different factors influence
      immunohistochemical results and gene amplification using DNA and mRNA. We
      recommend, based on data from this comprehensive analysis, a 10% neutral buffered
      formalin and fixation times of no longer than 1 week to produce consistent
      immunohistochemical slides and DNA amplification within 500 bp in pathology
      laboratories. 

PMID- 24888772
TI  - Hypertension, snoring, and obstructive sleep apnoea during pregnancy: a cohort
      study.
AB  - OBJECTIVE: To assess the frequency of obstructive sleep apnoea among women with
      and without hypertensive disorders of pregnancy. DESIGN: Cohort study. SETTING:
      Obstetric clinics at an academic medical centre. POPULATION: Pregnant women with
      hypertensive disorders (chronic hypertension, gestational hypertension, or pre
      eclampsia) and women who were normotensive. METHODS: Women completed a
      questionnaire about habitual snoring and underwent overnight ambulatory
      polysomnography. MAIN OUTCOME MEASURES: The presence and severity of obstructive
      sleep apnoea. RESULTS: Obstructive sleep apnoea was found among 21 of 51 women
      with hypertensive disorders (41%), but in only three of 16 women who were
      normotensive (19%, chi-square test, P=0.005). [Author correction added on 16 June
      2014, after first online publication: Results mentioned in the abstract were
      amended.] Non-snoring women with hypertensive disorders typically had mild
      obstructive sleep apnoea, but >25% of snoring women with hypertensive disorders
      had moderate to severe obstructive sleep apnoea. Among women with hypertensive
      disorders, the mean apnoea/hypopnoea index was substantially higher in snorers
      than in non-snorers (19.9+/-34.1 versus 3.4+/-3.1, P=0.013), and the
      oxyhaemoglobin saturation nadir was significantly lower (86.4+/-6.6 versus 90.2+/
      3.5, P=0.021). Among women with hypertensive disorders, after stratification by
      obesity, the pooled relative risk for obstructive sleep apnoea in snoring women
      with hypertension compared with non-snoring women with hypertension was 2.0 (95%
      CI 1.4-2.8). CONCLUSIONS: Pregnant women with hypertension are at high risk for
      unrecognised obstructive sleep apnoea. Although longitudinal and intervention
      studies are urgently needed, given the known relationship between obstructive
      sleep apnoea and hypertension in the general population, it would seem pertinent
      that hypertensive pregnant women who snore should be tested for obstructive sleep
      apnoea, a condition believed to cause or promote hypertension.

PMID- 24888775
TI  - Mucinous breast carcinoma with a lobular neoplasia component: a subset with
      aberrant expression of cell adhesion and polarity molecules and lack of
      neuroendocrine differentiation.
AB  - We investigated whether some mucinous carcinomas (MUCs) are associated with
      lobular neoplasia (LN) components, and if so, whether this subset has any
      distinct biological properties. MUC specimens from 41 patients were stratified
      into pure and mixed types. The LN components adjacent to MUC lesions were
      examined histopathologically. We also tested immunohistochemically for E
      cadherin, beta-catenin, and the neuroendocrine markers chromogranin A and
      synaptophysin; and compared results between MUCs with and without LN. Of 41
      patients with MUC, LN was detected in 12 patients (29%); LN alone was the
      noninvasive component in 8 patients (20%). Decreased E-cadherin and beta-catenin
      expression in the MUC component was detected in 2 (17%) and 7 (58%) cases,
      respectively, of MUC with LN, compared with 0% (P = 0.080) and 21% (P = 0.018) in
      MUCs without LN. Neuroendocrine factors were frequently detected in MUCs with LN
      (42%) and without LN (52%), but tended to be less frequent in MUCs with only LN
      components (25%) than in other MUCs (55%; P = 0.133). MUCs associated with LN
      components appear to be a biologically characteristic subset that frequently
      shows decreased cell-cell adhesion, cell polarity molecules and lack of
      neuroendocrine differentiation. 

PMID- 24888776
TI  - Community-acquired lobar pneumonia caused by Pseudomonas aeruginosa infection in
      Japan: a case report with histological and immunohistochemical examination.
AB  - Pseudomonas aeruginosa is a common pathogen in nosocomial and/or healthcare
      associated pneumonia, but is rare in community-acquired pneumonia. A 50-year-old
      previously healthy woman was taken to the emergency department because of rapidly
      progressing dyspnea. Chest radiograph showed consolidation of the entire right
      upper lobe, a finding suggestive of lobar pneumonia. The patient died of
      respiratory failure with bronchial bleeding, on the same day of admission.
      Autopsy revealed that the alveoli throughout the upper right lobe were filled
      with dense inflammatory cells mainly consisting of macrophages and neutrophils.
      Immunoreactive bacilli by using an anti-P. aeruginosa antibody were localized
      within macrophages accumulated in the alveoli as well in the vessel walls. Lobar
      pneumonia composed of dense neutrophils and bacteria-laden macrophages with total
      lung congestion and edema may be characteristic for community-acquired P.
      aeruginosa pneumonia in a healthy adult. 

PMID- 24888778
TI  - Angiofibroma of soft tissue with fibrohistiocytic features and intratumor genetic
      heterogeneity of NCOA2 gene rearrangement revealed by chromogenic in situ
      hybridization: a case report.
AB  - Angiofibroma of soft tissue is a recently described soft tissue tumor that is
      characterized by fibroblastic spindle tumor cells with arborizing capillary
      proliferation. Cytogenetically, it harbors a specific fusion gene involving the
      nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new
      pathological and cytogenetic features. A soft tissue tumor in the left thigh of
      73-year-old female was investigated. Microscopically, histiocytoid tumor cells
      were scattered in an edematous background with branching capillary proliferation.
      Immunohistochemically, we identified that the tumor cells were positive for
      histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was
      detected successfully by chromogenic in situ hybridization; however, abnormal
      signal patterns were observed in only a small subset of tumor cells. Unlike
      typical tumors with bland spindle cells, the present tumor needs to be
      distinguished from myxoid, dendritic and clear cell tumors. This case may suggest
      that angiofibroma of soft tissue is not in the center of the
      fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic
      nature. We also found intratumor genetic heterogeneity, which is uncommon for a
      translocation-associated tumor. Therefore, careful evaluation is required to
      detect the gene rearrangement in this tumor entity. 

PMID- 24888777
TI  - Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex
      ligation-dependent probe amplification and fluorescence in situ hybridization.
AB  - A needle biopsy of a mass in the right breast of a 36-year-old woman revealed
      invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed
      unequivocal membranous staining with the HercepTest. After systemic therapy with
      trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin +
      cyclophosphamide), a right mastectomy was performed. By histological and
      immunohistochemical examinations, the resected tumor consisted mainly of E
      cadherin-negative invasive lobular carcinoma (ILC), and the rest was ERBB2
      positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma.
      Multiplex ligation-dependent probe amplification and fluorescence in situ
      hybridization (FISH) analyses revealed that ILC and IDC shared high-level
      amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had
      an additional HSR-type amplicon of ERBB2. These findings strongly indicate that
      IDC and ILC had a common precursor cell with CCND1 amplification. Review of the
      biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2
      as a minor component, IDC without amplification of CCND1 or ERBB2 as a major
      component, and a minute portion of ILC with CCND1 amplification. We speculate
      that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC
      with CCND1 amplification was resistant to chemotherapy and grew. 

PMID- 24888779
TI  - delta-Catenin as a potential cancer biomarker.

PMID- 24888780
TI  - Renal sclerosing perivascular epithelioid cell tumor (PEComa)/angiomyolipoma with
      extensive rhabdoid cell features.

PMID- 24888784
TI  - A systematic review of interventions to promote physical activity in the
      preschool setting.
AB  - PURPOSE: Conduct a systematic review of school-based interventions to promote
      physical activity in preschoolers. DESIGN AND METHODS: A systematic search of
      literature between 2002 and 2014 in nine electronic databases and reference lists
      was conducted using the terms physical activity combined with environment,
      children, or interventions. RESULTS: Fourteen articles were identified.
      Interventions were environmental, cognitive/behavioral, or a combination.
      Positive interventions involving preschool children included manipulation of the
      playground with the number of children playing at one time, markings, or
      equipment, and goal setting and reinforcement. PRACTICE IMPLICATIONS: More
      research is needed to determine interventions to promote physical activity in
      preschool children.

PMID- 24888783
TI  - Divergent neuronal circuitries underlying acute orexigenic effects of peripheral
      or central ghrelin: critical role of brain accessibility.
AB  - Ghrelin is an octanoylated peptide hormone that potently and rapidly increases
      food intake. The orexigenic action of ghrelin involves the hypothalamic arcuate
      nucleus (ARC), which is accessible to plasma ghrelin and expresses high levels of
      the ghrelin receptor. Local administration of ghrelin in a variety of other brain
      nuclei also increases food intake. It is currently unclear, however, whether
      these non-ARC ghrelin brain targets are impacted by physiological increases of
      plasma ghrelin. Thus, the present study aimed to clarify which ghrelin brain
      targets participate in the short-term orexigenic actions of ghrelin. First, c-Fos
      induction into mouse brains centrally or peripherally treated with ghrelin was
      analysed. It was confirmed that peripherally administered ghrelin dose
      dependently increases food intake and mainly activates c-Fos in ARC neurones. By
      contrast, centrally administered ghrelin activates c-Fos in a larger number of
      brain nuclei. To determine which nuclei are directly accessible to ghrelin, mice
      were centrally or peripherally injected with a fluorescent ghrelin tracer. It was
      found that peripherally injected tracer mainly accesses the ARC, whereas
      centrally injected tracer reaches most brain areas known to express ghrelin
      receptors. Subsequently, the effects of ghrelin were tested in ARC-ablated mice
      and it was found that these mice failed to increase food intake in response to
      peripherally administered ghrelin but fully responded to centrally administered
      ghrelin. ARC-ablated mice showed patterns of ghrelin-induced c-Fos expression
      similar to those seen in control mice with the exception of the ARC, where no c
      Fos was found. Thus, peripheral ghrelin mainly accesses the ARC, which is
      required for the orexigenic effects of the hormone. Central ghrelin accesses a
      variety of nuclei, which can mediate the orexigenic effects of the hormone, even
      in the absence of an intact ARC. 

PMID- 24888781
TI  - Cutaneous glucocorticosteroidogenesis: securing local homeostasis and the skin
      integrity.
AB  - Human skin has the ability to synthesize glucocorticoids de novo from cholesterol
      or from steroid intermediates of systemic origin. By interacting with
      glucocorticoid receptors, they regulate skin immune functions as well as
      functions and phenotype of the epidermal, dermal and adnexal compartments. Most
      of the biochemical (enzyme and transporter activities) and regulatory
      (neuropeptides mediated activation of cAMP and protein kinase A dependent
      pathways) principles of steroidogenesis in the skin are similar to those
      operating in classical steroidogenic organs. However, there are also significant
      differences determined by the close proximity of synthesis and action (even
      within the same cells) allowing para-, auto- or intracrine modes of regulation.
      We also propose that ultraviolet light B (UVB) can regulate the availability of 7
      dehydrocholesterol for transformation to cholesterol with its further metabolism
      to steroids, oxysterols or ?7 steroids, because of its transformation to vitamin
      D3. In addition, UVB can rearrange locally produced ?7 steroids to the
      corresponding secosteroids with a short- or no-side chain. Thus, different
      mechanisms of regulation occur in the skin that can be either stochastic or
      structuralized. We propose that local glucocorticosteroidogenic systems and their
      regulators, in concert with cognate receptors operate to stabilize skin
      homeostasis and prevent or attenuate skin pathology.

PMID- 24888785
TI  - Acceleration of modern acidification in the South China Sea driven by
      anthropogenic CO2.
AB  - Modern acidification by the uptake of anthropogenic CO2 can profoundly affect the
      physiology of marine organisms and the structure of ocean ecosystems. Centennial
      scale global and regional influences of anthropogenic CO2 remain largely unknown
      due to limited instrumental pH records. Here we present coral boron isotope
      inferred pH records for two periods from the South China Sea: AD 1048-1079 and AD
      1838-2001. There are no significant pH differences between the first period at
      the Medieval Warm Period and AD 1830-1870. However, we find anomalous and
      unprecedented acidification during the 20th century, pacing the observed increase
      in atmospheric CO2. Moreover, pH value also varies in phase with inter-decadal
      changes in Asian Winter Monsoon intensity. As the level of atmospheric CO2 keeps
      rising, the coupling global warming via weakening the winter monsoon intensity
      could exacerbate acidification of the South China Sea and threaten this expansive
      shallow water marine ecosystem. 

PMID- 24888786
TI  - [Computer aided dosage management of phenprocoumon anticoagulation therapy.
      Clinical validation].
AB  - A recently developed multiparameter computer-aided expert system (TheMa) for
      guiding anticoagulation with phenprocoumon (PPC) was validated by a prospective
      investigation in 22 patients. The PPC-INR-response curve resulting from physician
      guided dosage was compared to INR values calculated by "twin calculation" from
      TheMa recommended dosage. Additionally, TheMa was used to predict the optimal
      time to perform surgery or invasive procedures after interruption of
      anticogulation therapy. RESULTS: Comparison of physician and TheMa guided
      anticoagulation showed almost identical accuracy by three quantitative measures:
      Polygon integration method (area around INR target) 616.17 vs. 607.86, INR hits
      in the target range 166 vs. 161, and TTR (time in therapeutic range) 63.91 vs.
      62.40 %. After discontinuation of anticoagulation therapy, calculating the INR
      phase-out curve with TheMa INR prognosis of 1.8 was possible with a standard
      deviation of 0.50 +/- 0.59 days. CONCLUSION: Guiding anticoagulation with TheMa
      was as accurate as Physician guided therapy. After interruption of anticoagulant
      therapy, TheMa may be used for calculating the optimal time performing operations
      or initiating bridging therapy.

PMID- 24888787
TI  - Impact of oxygen free radicals in rat partial liver transplantation.
AB  - BACKGROUND: Due to the shortage of suitable organs, the demand for partial liver
      transplantation from living donors has increased worldwide. N-acetylcysteine
      (NAC) has shown protective effects as a free radical scavenger during hypothermic
      preservation and warm ischemia-reperfusion liver injury; however, no study has
      reported the effects in partial liver transplantation. The aim of this study was
      to analyze the impact of NAC on liver graft microcirculation and graft function
      after partial liver transplantation in rats. METHODS: Orthotopic partial liver
      transplantations were performed in 40 rats following cold storage in histidine
      tryptophan-ketoglutarate solution for 3 h with 20 mM NAC (NAC group, n = 20) or
      without (control group, n = 20). We assessed portal circulation, graft
      microcirculation, and biochemical analyses of plasma at 1, 3, 24, and 168 h after
      portal reperfusion. RESULTS: (Control versus NAC, median and range): Portal
      venous pressure was significantly lower with NAC (P = 0.03). Microcirculation
      measured by laser Doppler was significantly improved with NAC throughout the time
      course (P = 0.003). Alanine aminotransferase levels were significantly lower in
      the NAC group (P < 0.05). Total antioxidative capacity was significantly higher
      in the NAC group at 1 h after reperfusion (Trolox equivalents: median, 3 MUM;
      range, 2.9-6.7 versus median, 16.45 MUM; range, 10.4-18.8). Lipid peroxidation
      was significantly abrogated in the NAC group (median, 177.6 nmol/mL; range, 75.9
      398.1 versus median, 71.5 nmol/mL; range, 58.5-79 at 3 h). CONCLUSIONS: This
      study showed that NAC treatment during cold storage resulted in improved
      microcirculation and preservation quality of partial liver graft likely because
      of enhanced antioxidant capacity and reduced lipid peroxidation.

PMID- 24888788
TI  - Comparing five simple vascular storage protocols.
AB  - BACKGROUND: We aim to find a storage protocol for vessels that preserves their
      dimensional, histologic, and mechanical characteristics to facilitate
      reproducible anastomosis experiments and microsurgical training with constant
      quality. MATERIALS AND METHODS: We compared stored rabbit aortas, harvested in a
      slaughterhouse, using five different protocols with fresh controls. Aortas were
      preserved for 125 d in (1) NaCl 0.9% at -18 degrees C, (2) Roswell Park Memorial
      Institute 1640 90% with 10% dimethyl sulfoxide (RPMI/DMSO) at -18 degrees C, (3)
      RPMI/DMSO at -70 degrees C, (4) glycerol 85% at 4 degrees C, and (5) glycerol in
      stepwise increased concentrations until 85% at 4 degrees C. After preservation,
      we measured vessel diameter, wall thickness, and Young's Modulus indicating
      stiffness. Neurosurgeons compared stored vessels with fresh vessels, blinded for
      preservation subgroup. We performed histologic assessment blinded for
      preservation subgroup. RESULTS: Fresh rabbit aortas showed a mean diameter of
      2.65 +/- 0.14 mm, a mean wall thickness of 126 +/- 22 MUm, and a Young's Modulus
      of 11.4 +/- 2.4 N/mm(2). NaCl 0.9%-preserved aortas showed a significantly
      increased vessel diameter and decreased stiffness. RPMI/DMSO-preserved aortas
      showed no significant differences from fresh aortas in dimensions and mechanical
      characteristics. Glycerol-preserved tissue showed a significant increase in wall
      thickness, a related significant decrease in diameter, and increase in stiffness.
      Neurosurgeons regarded RPMI/DMSO tissue as most comparable with fresh tissue.
      Histologic assessment revealed no differences between the different protocols and
      fresh control group. CONCLUSIONS: Storage of rabbit aortas in RPMI/DMSO most
      adequately preserves their dimensional and mechanical properties.

PMID- 24888789
TI  - Association between telomerase reverse transcriptase rs2736100 polymorphism and
      risk of glioma.
AB  - BACKGROUND: Epidemiological studies have been conducted to investigate the
      association of telomerase reverse transcriptase (TERT) rs2736100 polymorphism
      with glioma risk. The aim of the present study was to evaluate the association of
      TERT rs2736100 polymorphism with glioma risk using a meta-analysis approach.
      MATERIALS AND METHODS: All eligible studies were identified through a search of
      PubMed, EMBASE, China National Knowledge Infrastructure, Database of Chinese
      Scientific and Technical Periodicals, and China Biology Medical literature
      database before January 2014. The association between the TERT rs2736100
      polymorphism and glioma risk was estimated by odds ratio (OR) and 95% confidence
      interval (CI). RESULTS: A total of nine case-control studies including 9411 cases
      and 13,708 controls were eventually collected. Overall, we found that TERT
      rs2736100 polymorphism was significantly associated with the risk of glioma (OR =
      1.29, 95% CI 1.24-1.34, P < 0.001). In the subgroup analysis based on ethnicity,
      the significant association was found in Caucasians (OR = 1.29, 95% CI 1.24-1.34,
      P < 0.001). In subgroup analyses by histology, the associations were significant
      in glioblastoma (OR = 1.45, 95% CI 1.32-1.60, P < 0.001), astrocytoma (OR = 1.41,
      95% CI 1.26-1.58, P < 0.001), and oligodendroglioma (OR = 1.20, 95% CI 1.05-1.37,
      P = 0.008). CONCLUSIONS: Taken together, these data suggested that TERT rs2736100
      polymorphism may contribute to glioma susceptibility.

PMID- 24888790
TI  - MRSA-colonized persons' and healthcare personnel's experiences of patient
      professional interactions in and responsibilities for infection prevention in
      Sweden.
AB  - BACKGROUND: Patient-professional interactions and adherence to infection control
      measures are central to the quality of care and patient safety in healthcare.
      Persons colonized with methicillin-resistant Staphylococcus aureus (MRSA)
      describe insufficient support and unprofessional behavior among healthcare
      personnel. METHODS: A descriptive qualitative study was conducted to investigate
      managers', physicians', registered nurses' and MRSA-colonized persons'
      experiences of patient-professional interactions in relation to and
      responsibilities for infection prevention in the care of colonized patients. Five
      persons with MRSA colonization and 20 healthcare personnel employed within
      infection, hematology, nephrology or primary healthcare settings participated.
      The data were collected using open-ended semi-structured individual interviews
      with the MRSA-colonized persons and semi-structured focus group interviews with
      the healthcare personnel. RESULTS: The participants perceived MRSA as an
      indefinable threat and described that the responsibility for infection prevention
      is important, but such adherence was a neglected and negotiable issue. The
      described actions that were acknowledged as unprofessional and inappropriate
      adherence to infection prevention resulted in stigmatized patients. CONCLUSION:
      Colonized persons' and healthcare personnel's understanding of MRSA determines
      whether the personnel's behavior is perceived as proper or improper. Individual
      responsibility for patient-professional interactions in relation to MRSA
      colonization and adherence to infection control measures should be more
      stringent.

PMID- 24888791
TI  - Health-related quality of life in adult inpatients affected by anorexia nervosa.
AB  - OBJECTIVE: Poor awareness of illness in anorexia nervosa (AN) may render the
      assessment of health-related quality of life (HRQoL) difficult. We aimed at
      evaluating severe AN patients' HRQoL at discharge using different instruments and
      correlating this measure with clinical variables. METHODS: We enrolled 71 adult
      AN inpatients admitted through the emergency department. At admission, all
      participants completed the following: Medical Outcome Short Form Health Survey,
      Eating Disorder Inventory-2 and Temperament and Character Inventory. At admission
      and discharge, body mass index, EuroQoL Health Questionnaire/Visual Analogue
      Scale and Clinical Global Impression were evaluated. RESULTS: The HRQoL was
      severely impaired at baseline, but it improved at discharge. HRQoL correlated
      with eating psychopathology and personality, but not with body mass index or
      Clinical Global Impression. CONCLUSION: The HRQoL effectively captured patients'
      improvement at discharge. Given its correlations with clinical variables, this
      instrument may be useful in clinical practice.

PMID- 24888792
TI  - Impact of routinely employed procedures for tissue processing on the proteomic
      analysis of formalin-fixed paraffin-embedded tissue.
AB  - PURPOSE: FFPE (formalin fixed, paraffin embedded) tissue cohorts represent an
      enduring archive of clinical specimens. Proteomic analysis of FFPE tissues is
      gaining interest for the in-depth analysis of aberrant proteome composition.
      Procedures for FFPE tissue processing are standardized but there is diversity
      regarding the different processing systems. This work focuses on three different
      processing methods commonly used in large European pathology institutes.
      EXPERIMENTAL DESIGN: Formalin fixed tissue specimens of different tumors were
      serially sliced and processed with three different processing systems (xylene,
      ethanol/vacuum or microwave based). After paraffin embedding, they were subjected
      to MS-based proteomic analysis to investigate the impact of tissue processing
      techniques on the quality of proteomic analysis. Results were compared with
      proteomic analysis of corresponding cryopreserved tissue specimens. RESULTS: All
      processing techniques achieved very good proteome coverage similar to the
      cryopreserved counterpart. Gene ontology profiles, relative protein abundances,
      and peptide modifications such as methionine oxidation or proteolytic truncation
      were highly similar for all techniques as well as for the cryopreserved samples.
      CONCLUSIONS AND CLINICAL RELEVANCE: The results show that different processing
      procedures do not impede proteomic analysis as a robust and powerful approach for
      the identification of protein determinants and markers of disease processes and
      highlights the general robustness of FFPE-tissue based proteomics.

PMID- 24888793
TI  - Presentation of atrial fibrillation following oral dexamethasone treatment in a
      NF2 patient.
AB  - Atrial fibrillation (A-fib) is the most common cardiac arrhythmia which is
      associated with an increased risk of mortality secondary to stroke and coronary
      artery disease. Intravenous glucocorticoid therapy (such as dexamethasone and
      hydrocortisone) is frequently used peri-operatively in patients undergoing
      cardiac surgery to prevent A-fib. Dexamethasone is also frequently used in
      patients with single or bilateral vestibular schwannomas (VS), to reduce tumor
      swelling both before and after radiation treatment. We describe a case of A-fib
      in a 50 year-old female patient with neurofibromatosis type 2 (NF-2), who was
      prescribed dexamethasone for post-radiation tumor edema.

PMID- 24888795
TI  - The safety of tracheostomy speaking valve use during sleep in children: a pilot
      study.
AB  - PURPOSE: One of the disadvantages of having a tracheostomy tube is not being able
      to vocalize. A speaking valve connected to a tracheostomy tube allows patients to
      vocalize. Some studies have shown that tracheostomy-speaking valve can improve
      swallowing, respiratory secretion management, and expedite decannulation. There
      is scant research about speaking valve use during sleep. The aim of this study is
      to evaluate the safety of tracheostomy-speaking valve overnight, during sleep.
      MATERIALS AND METHODS: Children, ages 1-18 years, with tracheostomy tubes who
      were using a tracheostomy-speaking valve during daytime/awake periods, were
      included in this study. The subjects had baseline monitoring of their heart rate,
      respiratory rate, oxygen saturation, and end tidal carbon dioxide measurement the
      night prior to the intervention, throughout the night at scheduled intervals. The
      tracheostomy-speaking valve was placed the following night and the same
      parameters were monitored and recorded throughout the study night. RESULTS: A
      total of 9 patients were recruited. In all subjects, the mean values of the
      overnight parameters showed no significant clinical variations between the
      baseline night and the study night. Repeated measure ANOVA analysis revealed no
      significant changes in the parameters over the 8 hours of recorded time. No major
      adverse events were recorded during the study night. CONCLUSION: This pilot study
      reveals that use of a tracheostomy-speaking valve during sleep, was not
      associated with adverse cardiopulmonary events. This is the first study to show
      that a tracheostomy-speaking valve might be safely used during sleep, in
      children.

PMID- 24888794
TI  - Neurofibromatosis of the larynx causing stridor and sleep apnea.
AB  - BACKGROUND: Neurofibromatosis type 1 can rarely present in the larynx. Patients
      typically do not present with complete obstructive symptoms, but partial
      obstruction and stridor. We review our health centers' case series of two
      patients, the first of whom presented with persistent sleep apnea post
      tonsillectomy and adenoidectomy, and the second who presented with noisy
      breathing. Additionally, we will review the literature on the management and
      treatment options for children with this rare clinical entity. METHODS:
      Retrospective case review. CASE REPORT & RESULTS: A two-year old male underwent a
      sleep endoscopy following persistent evidence of obstructive sleep apnea on
      polysomnography after initial tonsillectomy and adenoidectomy. Family elicited
      concerns about noisy breathing at night and an accompanying video documented
      stridor while sleeping during the monitored polysomnography. Flexible fiberoptic
      laryngoscopy in the operating room revealed what appeared to be a cystic mass
      along the right aryepiglottic fold causing deviation of the laryngeal introitus
      towards the contralateral side. Subsequent direct laryngoscopy and excisional
      biopsy revealed pathology results consistent with a plexiform neurofibroma. A six
      month-old patient with stertor and stridor was found to have a laryngeal mass,
      subglottic stensosis, and progressive airway obstruction due to plexiform
      neurofirboma in the supraglottis, subglottis, and trachea. We present a series of
      two patients incidentally diagnosed with neurofibromatosis type 1 by way of a
      laryngeal neurofibroma and review the literature on management options. Both
      patients were found to have accompanying cafe au lait spots. Both patients
      required tracheostomy for airway management, and one was successfully
      decannulated. CONCLUSION: Laryngeal neurofibroma is a rare anomaly that can
      manifest with airway obstruction. Both patients presented here subsequently were
      noted to have cafe au lait spots on physical examination. The Otolaryngologist
      should be reminded of this anomaly when evaluating a child with evidence of a
      submucosal laryngeal mass. We present our series including that of a patient
      whose diagnosis was prompted by persistent sleep apnea following
      adenotonsillectomy tonsillectomy and a patient with airway obstruction and
      subglottic stenosis due to a neurofibroma. The treatment of choice is complete
      excision of the neurofibroma while maintaining functionality of the larynx. This
      can lead to successful decannulation.

PMID- 24888796
TI  - Is drain placement necessary in pediatric patients who undergo the Sistrunk
      procedure?
AB  - BACKGROUND: Thyroglossal duct cysts are usually managed with the Sistrunk
      procedure, which involves excision of the cervical cyst with the central portion
      of the hyoid bone, along with its tract. Surgical drains are commonly placed with
      this procedure, which necessitates postoperative hospital admission. OBJECTIVE:
      The aim of this study is to determine if surgical drain placement is necessary in
      pediatric patients who underwent the Sistrunk procedure. METHODS: The current
      study describes the outcomes of 30 consecutive children who underwent the
      Sistrunk procedure without drain placement. Complication rates are compared to an
      age-matched control group who had drains placed. RESULTS: No major complications,
      including hematomas were observed in the study group; outpatient surgery was
      safely observed in 20 patients. No significant difference in complication rates
      was observed between the study and control groups. CONCLUSIONS: Routine drain
      placement in children who are undergoing the Sistrunk procedure may not be
      necessary. Subsequently, postoperative admission may be avoided.

PMID- 24888798
TI  - Mix-ups and misconnections: avoiding intravenous line errors.

PMID- 24888797
TI  - A case of congenital aplasia of the epiglottis in an adult.
AB  - Aplasia or hypoplasia of the epiglottis in an adult is rarely reported congenital
      anomaly of the larynx. Most patients with epiglottic aplasia have presented fatal
      symptom of respiratory distress and severe aspiration in infancy or childhood. We
      present a case of congenital absence of the epiglottis found in a 33-year-old
      woman complaining of recurrent lingual tonsillitis. Laryngoscopic finding and CT
      scan revealed an isolated epiglottic aplasia and normal appearance of other
      laryngeal structure. This is the first description of physiologic evaluation in
      an epiglottic anomaly to find the compensatory mechanism of aspiration
      prevention. We discussed this case with a review of literature. 

PMID- 24888799
TI  - Trauma mortality: understanding mortality distribution to improve outcomes.

PMID- 24888800
TI  - Cancer-specific outcomes among young adults without health insurance.
AB  - PURPOSE: The Patient Protection and Affordable Care Act (ACA) will likely improve
      insurance coverage for most young adults, but subsets of young adults in the
      United States will face significant premium increases in the individual market.
      We examined the association between insurance status and cancer-specific outcomes
      among young adults. METHODS: We used the SEER program to identify 39,447 patients
      age 20 to 40 years diagnosed with a malignant neoplasm between 2007 and 2009. The
      association between insurance status and stage at presentation, employment of
      definitive therapy, and all-cause mortality was assessed using multivariable
      logistic or Cox regression, as appropriate. RESULTS: Patients who were uninsured
      were more likely to be younger, male, nonwhite, and unmarried than patients who
      were insured and were also more likely to be from regions of lower income,
      education, and population density (P < .001 in all cases). After adjustment for
      pertinent confounding variables, an association between insurance coverage and
      decreased likelihood of presentation with metastatic disease (odds ratio [OR],
      0.84; 95% CI, 0.75 to 0.94; P = .003), increased receipt of definitive treatment
      (OR, 1.95; 95% CI, 1.52 to 2.50; P < .001), and decreased death resulting from
      any cause (hazard ratio, 0.77; 95% CI, 0.65 to 0.91; P = .002) was noted.
      CONCLUSION: The improved coverage fostered by the ACA may translate into better
      outcomes among most young adults with cancer. Extra consideration will need to be
      given to ensure that patients who will face premium increases in the individual
      market can obtain insurance coverage under the ACA.

PMID- 24888801
TI  - Best treatment strategies in high-risk multiple myeloma: navigating a gray area.
AB  - A previously healthy 62-year-old man presented to his primary care physician with
      a 3-month history of fatigue and unremitting back pain. Physical examination
      revealed mucosal pallor, point tenderness at T10-T12, and a normal neurologic
      examination with preserved lower extremity strength and sphincter tone.
      Laboratory work-up disclosed hemoglobin 10.1 g/dL with mean corpuscular volume of
      101 fL and otherwise normal blood cell counts; reticulocytes, 0.98%; stable
      creatinine, 1.1 mg/dL; calcium, 9.1 mg/dL; albumin, 3.4 g/dL; beta2
      microglobulin, 5.7 mg/L; lactate dehydrogenase (LDH), 397 IU/L; and normal liver
      function tests. Bone survey showed lytic lesions at T10, T12, and throughout the
      axial skeleton and osteopenia. Serum protein electrophoresis (SPEP) demonstrated
      a 3.5 g/dL monoclonal peak in the gamma region, with monoclonal immunoglobulin G
      and lambda light chain detected on immunofixation. Serum free light chain (sFLC)
      ratio was 0.0001. Twenty-four-hour urine protein electrophoresis (UPEP) was
      normal. Bone marrow biopsy showed 60% infiltration with lambda light chain
      restricted plasma cells staining positive for CD138 and CD56 and negative for
      CD45 by flow cytometry (Fig 1). Congo red stain on bone marrow biopsy and fat pad
      aspirate was negative for amyloid light-chain deposition. Cytogenetics of the
      malignant cells identified a t(4;14) translocation, confirming the diagnosis of
      high-risk, International Staging System stage III immunoglobulin G lambda
      multiple myeloma (MM). The patient began treatment with lenalidomide, bortezomib,
      and dexamethasone (RVD) plus monthly intravenous zoledronic acid therapy. He has
      tolerated therapy well, and the monoclonal protein peak is rapidly declining. He
      is now referred to discuss indications for autologous stem-cell transplantation
      (ASCT) and overall prognosis.

PMID- 24888803
TI  - Systemic treatment of endometrial cancer: what is doxorubicin's role?

PMID- 24888804
TI  - Reply to M.g. Bare et al.

PMID- 24888805
TI  - Reply to M.G. Bare et al.

PMID- 24888802
TI  - Past, present, and future challenges in breast cancer treatment.

PMID- 24888806
TI  - Combination of international scoring system 3, high lactate dehydrogenase, and
      t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated
      with front-line autologous stem-cell transplantation at high risk of early MM
      progression-related death.
AB  - PURPOSE: To construct and validate among patients with multiple myeloma (MM) who
      were treated with intensive therapy a prognostic index of early MM progression
      related death. PATIENTS AND METHODS: Patient-level data from the Intergroupe
      Francophone du Myelome (IFM) 2005-01 trial (N = 482) were used to construct the
      prognostic index. The event was MM progression-related death within 2 years from
      treatment initiation. The index was validated using data from three other trials:
      the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) 26866138-MMY-3006
      trial (N = 480), the Programa para el Estudio de la Terapeutica en Hemopatia
      Maligna (PETHEMA)-GEMMENOS65 trial (N = 390), and the Hemato-Oncologie voor
      Volwassenen Nederland (HOVON) -65/German-Speaking Myeloma Multicenter Group
      (GMMG) -HD4 trial (N = 827). RESULTS: The risk of early MM progression-related
      death was related to three independent prognostic variables: lactate
      dehydrogenase (LDH) higher than than normal, International Staging System 3
      (ISS3), and adverse cytogenetics [t(4;14) and/or del(17p)]. These three variables
      enabled the definition of an ordinal prognostic classification composed of four
      scores (0 to 3). Patients with a score of 3, defined by the presence of t(4;14)
      and/or del(17p) in addition to ISS3 and/or high LDH, comprised 5% (20 of 387
      patients) to 8% (94 of 1,139 patients) of the patients in the learning and
      validation samples, respectively, and they had a very poor prognosis. When
      applied to the population of 855 patients who had received bortezomib-based
      induction therapy in the four trials, the prognostic classification was also able
      to segregate patients into four categories, with a very poor prognosis attributed
      to patients with a score of 3. CONCLUSION: Our model allows the simple definition
      of a subgroup of MM patients at high risk of early MM progression-related death
      despite the use of the most modern and effective strategies.

PMID- 24888807
TI  - Omission of sexual and gender minority patients.

PMID- 24888809
TI  - Policy decisions have consequences: sometimes unintended ones.

PMID- 24888808
TI  - Underuse of trimodality treatment affects survival for patients with inflammatory
      breast cancer: an analysis of treatment and survival trends from the National
      Cancer Database.
AB  - PURPOSE: To analyze factors that predict the use of trimodality treatment
      (chemotherapy, surgery, and radiation therapy [RT]) and evaluate the impact that
      trimodality treatment use has on survival for patients with inflammatory breast
      cancer (IBC). METHODS: Using the National Cancer Data Base, patients who
      underwent surgical treatment of nonmetastatic IBC from 1998 to 2010 were
      identified. We collected demographic, tumor, and treatment data and analyzed
      treatment and survival trends over time. Logistic regression and Cox proportional
      hazard models were used to examine factors predicting treatment and survival.
      RESULTS: We identified 10,197 patients who fulfilled study criteria. The use of
      trimodality therapy fluctuated annually (58.4% to 73.4%). Patients who were
      older, diagnosed earlier in the study period, lived in regions of the country
      outside of the Midwest, had lower incomes or public insurance, and had a higher
      comorbid score were significantly less likely to receive trimodality therapy (all
      P < .05). Five- and 10-year survival rates were highest among patients receiving
      trimodality treatment (55.4% and 37.3%, respectively) compared with patients who
      received the combination of surgery plus chemotherapy, surgery plus RT, or
      surgery alone. After adjusting for potential confounding variables, use of
      trimodality therapy remained a significant independent predictor of survival.
      CONCLUSION: Underutilization of trimodality therapy negatively impacted survival
      for patients with IBC. The use of trimodality therapy increased marginally with
      time, but there remain significant factors associated with differences in use of
      trimodality treatment. We have identified specific barriers to care that may be
      targeted to improve treatment delivery and potentially improve patient outcomes.

PMID- 24888811
TI  - How low should we go? The search for balance in management of small human
      epidermal growth factor receptor 2-positive breast cancers.

PMID- 24888810
TI  - Randomized, phase III trial of first-line figitumumab in combination with
      paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients
      with advanced non-small-cell lung cancer.
AB  - PURPOSE: Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal
      antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our
      multicenter, randomized, phase III study compared figitumumab plus chemotherapy
      with chemotherapy alone as first-line treatment in patients with advanced non
      small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV
      or recurrent NSCLC disease with nonadenocarcinoma histology received open-label
      figitumumab (20 mg/kg) plus paclitaxel (200 mg/m(2)) and carboplatin (area under
      the concentration-time curve, 6 mg . min/mL) or paclitaxel and carboplatin alone
      once every 3 weeks for up to six cycles. The primary end point was overall
      survival (OS). RESULTS: Of 681 randomly assigned patients, 671 received
      treatment. The study was closed early by an independent Data Safety Monitoring
      Committee because of futility and an increased incidence of serious adverse
      events (SAEs) and treatment-related deaths with figitumumab. Median OS was 8.6
      months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone
      (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free
      survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4),
      respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%,
      respectively. The respective rates of all-causality SAEs were 66% and 51%; P <
      .01). Treatment-related grade 5 adverse events were also more common with
      figitumumab (5% v 1%; P < .01). CONCLUSION: Adding figitumumab to standard
      chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma
      NSCLC. Further clinical development of figitumumab is not being pursued.

PMID- 24888812
TI  - Complete Response of Metastatic Androgen Receptor-Positive Breast Cancer to
      Bicalutamide: Case Report and Review of the Literature.

PMID- 24888814
TI  - Barriers to immediate breast reconstruction in the Canadian universal health care
      system.
AB  - PURPOSE: To describe the population-based rates of immediate breast
      reconstruction (IBR) for all women undergoing mastectomy for treatment or
      prophylaxis of breast cancer in the past decade, and to evaluate geographic,
      institutional, and patient factors that influence use in the publically funded
      Canadian health care system. METHODS: This population-based retrospective cohort
      study used administrative data that included 28,176 women who underwent
      mastectomy (25,141 mastectomy alone and 3,035 IBR) between April 1, 2002, and
      March 31, 2012, in Ontario, Canada. We evaluated factors associated with IBR by
      using a multivariable logistic regression model with the generalized estimating
      equation approach. RESULTS: The population-based, age-adjusted IBR rate increased
      from 5.1 procedures to 8.7 in 100,000 adult women (43.7%; P < .001), and the
      increase was greatest for prophylactic mastectomy or therapeutic mastectomy for
      in situ breast cancer (78.6%; P < .001). Women who lived in neighborhoods with
      higher median income had significantly increased odds of IBR compared with
      mastectomy alone (odds ratio [OR], 1.71; 95% CI, 1.47 to 2.00), and immigrant
      women had significantly lower odds (OR, 0.59; 95% CI, 0.44 to 0.78). A patient
      had nearly twice the odds of receiving IBR when she was treated at a teaching
      hospital (OR, 1.84; 95% CI, 1.1 to 3.06) or at a hospital with two or more
      available plastic surgeons (OR, 2.01; 95% CI, 1.53 to 2.65). Patients who
      received IBR traveled significantly farther compared with those who received
      mastectomy alone (OR, 1.04; 95% CI, 1.02 to 1.05 for every 10 km increase).
      CONCLUSION: IBR is available to select patients with favorable clinical and
      demographic characteristics who travel farther to undergo surgery at teaching
      hospitals with two or more available plastic surgeons.

PMID- 24888813
TI  - Antigen-specific immune responses and clinical outcome after vaccination with
      glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized
      by lysine and carboxymethylcellulose in children with newly diagnosed malignant
      brainstem and nonbrainstem gliomas.
AB  - PURPOSE: Diffuse brainstem gliomas (BSGs) and other high-grade gliomas (HGGs) of
      childhood carry a dismal prognosis despite current treatments, and new therapies
      are needed. Having identified a series of glioma-associated antigens (GAAs)
      commonly overexpressed in pediatric gliomas, we initiated a pilot study of
      subcutaneous vaccinations with GAA epitope peptides in HLA-A2-positive children
      with newly diagnosed BSG and HGG. PATIENTS AND METHODS: GAAs were EphA2,
      interleukin-13 receptor alpha 2 (IL-13Ralpha2), and survivin, and their peptide
      epitopes were emulsified in Montanide-ISA-51 and given every 3 weeks with
      intramuscular polyinosinic-polycytidylic acid stabilized by lysine and
      carboxymethylcellulose for eight courses, followed by booster vaccinations every
      6 weeks. Primary end points were safety and T-cell responses against vaccine
      targeted GAA epitopes. Treatment response was evaluated clinically and by
      magnetic resonance imaging. RESULTS: Twenty-six children were enrolled, 14 with
      newly diagnosed BSG treated with irradiation and 12 with newly diagnosed BSG or
      HGG treated with irradiation and concurrent chemotherapy. No dose-limiting non
      CNS toxicity was encountered. Five children had symptomatic pseudoprogression,
      which responded to dexamethasone and was associated with prolonged survival. Only
      two patients had progressive disease during the first two vaccine courses; 19 had
      stable disease, two had partial responses, one had a minor response, and two had
      prolonged disease-free status after surgery. Enzyme-linked immunosorbent spot
      analysis in 21 children showed positive anti-GAA immune responses in 13: to IL
      13Ralpha2 in 10, EphA2 in 11, and survivin in three. CONCLUSION: GAA peptide
      vaccination in children with gliomas is generally well tolerated and has
      preliminary evidence of immunologic and clinical responses. Careful monitoring
      and management of pseudoprogression is essential.

PMID- 24888815
TI  - Distant invasive breast cancer recurrence risk in human epidermal growth factor
      receptor 2-positive T1a and T1b node-negative localized breast cancer diagnosed
      from 2000 to 2006: a cohort from an integrated health care delivery system.
AB  - PURPOSE: To determine the invasive recurrence (IR) risk among patients with
      small, node-negative human epidermal growth factor receptor 2 (HER2) -positive
      breast cancer. PATIENTS AND METHODS: Among 16,975 consecutive patients with
      invasive breast cancer diagnosed from January 1, 2000, to December 31, 2006, in a
      large, integrated health care system, we identified a cohort of 234 patients with
      HER2-positive T1aN0M0 or T1bN0M0 (T1abN0M0) disease with a median follow-up of
      5.8 years. Kaplan-Meier methods were used to estimate the percentage of patients
      who were free of invasive recurrence (recurrence-free interval [RFI]) at 5 years
      for both distant (DRFI) and local (LRFI) recurrences. RESULTS: Of 15 IRs, 47%
      were locoregional only. Among T1ab patients not treated with adjuvant trastuzumab
      or chemotherapy (n = 171), the 5-year invasive DRFI was 98.2% (95% CI, 94.5% to
      99.4%); it was 99.0% (95% CI, 93.0% to 99.9%) for T1a patients, and 97.0% (95%
      CI, 88.6% to 99.2%) for T1b patients. Locoregional plus distant 5-year invasive
      RFI was 97.0% (95% CI, 90.9% to 99.0%) for T1a and 91.9% (95% CI, 81.5% to 96.6%)
      for T1b patients; it was 89.4% (95% CI, 70.6% to 96.5%) for T1b tumors reported
      at 1.0 cm. T1b tumors reported at 1.0 cm accounted for 24% of the T1ab cohort,
      61% of the cohort total tumor volume, and 75% of distant recurrences. Invasive
      RFI for T1b 1.0 cm tumors was lower than that for T1a tumors: 84.5% versus 97.4%
      (P = .009). CONCLUSION: The distant IR risk of T1a HER2-positive breast cancer
      appears quite low. The distant IR risk in T1b patients, particularly those with
      1.0-cm tumors, is higher. Potential risk differences for T1a and T1b, including
      the 1.0-cm tumors, should be considered when making treatment decisions.

PMID- 24888817
TI  - Sketching the human experience.

PMID- 24888816
TI  - Outcomes by tumor subtype and treatment pattern in women with small, node
      negative breast cancer: a multi-institutional study.
AB  - PURPOSE: Treatment decisions for patients with T1a,bN0M0 breast cancer are
      challenging. We studied the time trends in use of adjuvant chemotherapy and
      survival outcomes among these patients. PATIENTS AND METHODS: This was a
      prospective cohort study within the National Comprehensive Cancer Network
      Database that included 4,113 women with T1a,bN0M0 breast cancer treated between
      2000 and 2009. Tumors were grouped by size (T1a, T1b), biologic subtype defined
      by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)
      status, and receipt of chemotherapy with or without trastuzumab. RESULTS: Median
      follow-up time was 5.5 years. Eight percent of patients with HR-positive/HER2
      negative tumors were treated with chemotherapy. Fifty-two percent of those with
      HER2-positive or HR-negative/HER2-negative breast cancers received chemotherapy,
      with an increase over the last decade. Survival outcomes diverged by subtype and
      size, but the 5-year distant relapse-free survival (DRFS) did not exceed 10% in
      any subgroup. The 5-year DRFS for patients with T1a tumors untreated with
      chemotherapy ranged from 93% to 98% (n = 49 to 972), and for patients with T1b
      tumors, it ranged from 90% to 96% (n = 17 to 2,005). Patients with HR
      positive/HER2-negative disease had the best DRFS estimates, and patients with HR
      negative/HER2-negative tumors had the lowest. In this observational,
      nonrandomized cohort study, the 5-year DRFS for treated patients with T1a tumors
      was 100% for all subgroups (n = 12 to 33), and for patients with T1b tumors, it
      ranged from 94% to 96% (n = 88 to 241). CONCLUSION: Women with T1a,b tumors have
      an excellent prognosis without chemotherapy. Size and tumor subtype may identify
      patients in whom the rate of recurrence justifies consideration of chemotherapy.
      These patients represent an optimal group for evaluating less toxic adjuvant
      regimens to maintain efficacy while minimizing short- and long-term risks.

PMID- 24888820
TI  - Towards a sustainable synthesis of formate salts: combined catalytic methanol
      dehydrogenation and bicarbonate hydrogenation.
AB  - Formate salts are important chemicals widely used in everyday products. The
      current industrial-scale manufacture of formates requires CO at high pressure and
      harsh reaction conditions. Herein, we describe a new process for these products
      without the utilization of hazardous gases and chemicals. By application of
      ruthenium pincer complexes, a simultaneous methanol dehydrogenation and
      bicarbonate hydrogenation reaction proceeds, which provides a green synthesis of
      formate salts with excellent TON (>18,000), TOF (>1300 h(-1)), and yield (>90%).

PMID- 24888818
TI  - Circulating tumor cells and response to chemotherapy in metastatic breast cancer:
      SWOG S0500.
AB  - PURPOSE: Increased circulating tumor cells (CTCs; five or more CTCs per 7.5 mL of
      whole blood) are associated with poor prognosis in metastatic breast cancer
      (MBC). A randomized trial of patients with persistent increase in CTCs tested
      whether changing chemotherapy after one cycle of first-line chemotherapy would
      improve the primary outcome of overall survival (OS). PATIENTS AND METHODS:
      Patients with MBC who did not have increased CTCs at baseline remained on initial
      therapy until progression (arm A). Patients with initially increased CTCs that
      decreased after 21 days of therapy remained on initial therapy (arm B). Patients
      with persistently increased CTCs after 21 days of therapy were randomly assigned
      to continue initial therapy (arm C1) or change to an alternative chemotherapy
      (arm C2). RESULTS: Of 595 eligible and evaluable patients, 276 (46%) did not have
      increased CTCs (arm A). Of those with initially increased CTCs, 31 (10%) were not
      retested, 165 were assigned to arm B, and 123 were randomly assigned to arm C1 or
      C2. No difference in median OS was observed between arm C1 and C2 (10.7 and 12.5
      months, respectively; P = .98). CTCs were strongly prognostic. Median OS for arms
      A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months,
      respectively (P < .001). CONCLUSION: This study confirms the prognostic
      significance of CTCs in patients with MBC receiving first-line chemotherapy. For
      patients with persistently increased CTCs after 21 days of first-line
      chemotherapy, early switching to an alternate cytotoxic therapy was not effective
      in prolonging OS. For this population, there is a need for more effective
      treatment than standard chemotherapy.

PMID- 24888821
TI  - Esophageal replacement: overcoming the need.
AB  - Three developments which have contributed to the declining necessity for
      esophageal replacement are improvement in the management of esophageal atresia,
      prevention of caustic injuries to the esophagus, and early antireflux surgery for
      intractable gastro-esophageal reflux. Despite these advances, replacement of the
      esophagus may still be necessary. The two most commonly used procedures for
      replacing the esophagus are colonic interposition and gastric transposition.
      Experience with 236 gastric transposition operations reveals a mortality of 2.5%,
      leak rate of 12%, and stricture of 20%. The follow-up shows a satisfaction of
      over 90%. New methods of overcoming the need for esophageal replacement are in
      progress with tissue engineering with a scaffold to produce a tubular graft to
      bridge the gap in the continuity of the esophagus. 

PMID- 24888822
TI  - Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with
      congenital lung masses.
AB  - PURPOSE: The purpose of this study was to evaluate fetal magnetic resonance
      imaging (MRI) as a modality for predicting perinatal outcomes and lung-related
      morbidity in fetuses with congenital lung masses (CLM). METHODS: The records of
      all patients treated for CLM from 2002 to 2012 were reviewed retrospectively.
      Fetal MRI-derived lung mass volume ratio (LMVR), observed/expected normal fetal
      lung volume (O/E-NFLV), and lesion-to-lung volume ratio (LLV) were calculated.
      Multivariate regression and receiver operating characteristic analyses were
      applied to determine the predictive accuracy of prenatal imaging. RESULTS: Of 128
      fetuses with CLM, 93% (n=118) survived. MRI data were available for 113 fetuses.
      In early gestation (<26weeks), MRI measurements of LMVR and LLV correlated with
      risk of fetal hydrops, mortality, and/or need for fetal intervention. In later
      gestation (>26weeks), LMVR, LLV, and O/E-NFLV correlated with neonatal
      respiratory distress, intubation, NICU admission and need for neonatal surgery.
      On multivariate regression, LMVR was the strongest predictor for development of
      fetal hydrops (OR: 6.97, 1.58-30.84; p=0.01) and neonatal respiratory distress
      (OR: 12.38, 3.52-43.61; p<=0.001). An LMVR >2.0 predicted worse perinatal outcome
      with 83% sensitivity and 99% specificity (AUC=0.94; p<0.001). CONCLUSION: Fetal
      MRI volumetric measurements of lung masses and residual normal lung are
      predictive of perinatal outcomes in fetuses with CLM. These data may assist in
      perinatal risk stratification, counseling, and resource utilization.

PMID- 24888819
TI  - Circulating IGF-axis protein levels and their relation with levels of plasma
      adipocytokines and macronutrient consumption in women.
AB  - OBJECTIVE: Circulating free insulin-like growth factor (IGF)-I and its binding
      proteins, most notably, IGFBP-1 and IGFBP-2, have been prospectively associated
      with incident type 2 diabetes in women. However, little is known regarding the
      factors that may influence these IGF-axis protein levels. The aim is to study the
      relation of IGF-axis protein levels with adipcytokines, macronutrient
      consumption, and other factors related to diabetes. DESIGN: Fasting plasma from
      558 controls enrolled in a nested case-control study within the Nurses' Health
      Study of incident type 2 diabetes in women was tested for: IGF-axis proteins
      (free and total IGF-I, IGFBP-1, IGFBP-2, IGFBP-3), adipocytokines (leptin,
      adiponectin, resistin), soluble leptin receptor (sOB-R), inflammatory factors (IL
      18 and C-reactive protein (CRP)), insulin, and glycated hemoglobin (HbA1C).
      RESULTS: In multivariate models, each 1% increase in sOB-R (mean 34.9ng/mL,
      standard deviation (SD) +/-11.3) was associated with -0.20% total IGF-I
      (P=0.0003) and -0.42% free IGF-I (P=0.002), as well as 0.73% higher IGFBP-1
      (P<0.0001) and 0.27% IGFBP-2 (P=0.003). For example, a one SD change from the
      mean sOB-R level was associated with 11% lower free IGF-I. Insulin levels (mean
      6.8MUU/mL+/-5.3) were inversely and adiponectin (mean 18.3MUg/mL+/-7.4)
      positively associated with IGFBP-1 and IGFBP-2 (all P<0.01). Consumption of dairy
      protein, monounsaturated fats, and saturated fats, was also correlated with IGF
      axis protein levels (all P<0.05). CONCLUSIONS: Several molecular factors and
      macronutrients were independently associated with plasma IGF-axis protein levels.
      Which of these, if any, reflect biologic relationships that can be intervened
      upon to influence IGF-axis protein concentrations warrants further investigation.

PMID- 24888823
TI  - Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a
      nitrofen explant model.
AB  - PURPOSE: Recent experimental work suggests the therapeutic role of mesenchymal
      stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to
      investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF
      MSCs) on fetal lung growth in a nitrofen explant model. METHODS: Pregnant Sprague
      Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung
      explants were subsequently harvested and cultured ex vivo for three days on
      filter membranes in conditioned media from rat AF-MSCs isolated from control (AF
      Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed
      morphometrically and by quantitative gene expression. RESULTS: Although there
      were no significant differences in total lung surface area among hypoplastic
      lungs, there were significant increases in terminal budding among E14.5+3
      nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone
      (58.8+/-8.4 vs. 39.0+/-10.0 terminal buds, respectively; p<0.05). In contrast,
      lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen
      explants exposed to AF-Ctr showed significant upregulation of surfactant protein
      C to levels observed in normal fetal lungs. CONCLUSIONS: AF-MSCs can augment
      branching morphogenesis and lung epithelial maturation in a fetal explant model
      of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a
      novel strategy for the treatment of fetal congenital diaphragmatic hernia.

PMID- 24888824
TI  - Increased uptake of dietary retinoids at the maternal-fetal barrier in the
      nitrofen model of congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: The retinol signaling pathway is disrupted in congenital
      diaphragmatic hernia (CDH). Since there is no fetal retinol synthesis, maternal
      retinol has to cross the placenta. Nitrofen interferes with the retinol-binding
      protein (RBP) transfer pathway in CDH. However, in RBP knockout mice, retinol has
      been shown to be present. In this model, increased uptake of maternal dietary
      retinyl ester (RE) bounded in low-dense-lipoprotein (LDL) through low-density
      lipoprotein-receptor 1 (LRP1) and increased activity of RE hydrolysis by
      lipoprotein-lipase (LPL) have been found. The aim of this study was to
      investigate the RE transfer pathway in the nitrofen CDH model. METHODS: Pregnant
      rats were treated with nitrofen or vehicle on gestational day (D9) and sacrificed
      on D21. Immunohistochemistry was performed to evaluate LRP1 and LPL protein
      expression. Serum LDL levels were measured by ELISA. Pulmonary and serum retinoid
      levels were measured using HPLC. RESULTS: Markedly increased trophoblastic and
      pulmonary LRP1 and LPL immunoreactivity were observed in CDH compared to
      controls. Significantly increased serum LDL and RE levels were observed in CDH
      compared to controls. CONCLUSIONS: The increased uptake of dietary retinoids at
      the maternal-fetal barrier in the nitrofen CDH model suggests that the RE
      transfer pathway may be the main source of retinol in this model.

PMID- 24888825
TI  - Upregulation of serotonin-receptor-2a and serotonin transporter expression in the
      pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.
AB  - PURPOSE: Congenital diaphragmatic hernia (CDH) is attributed to severe pulmonary
      hypoplasia and pulmonary hypertension (PH). PH is characterized by structural
      changes resulting in vascular remodeling. Serotonin, a potent vasoconstrictor,
      plays a central role in the development of PH. It exerts its constricting effects
      on the vessels via Serotonin receptor 2A (5-HT2A) and induces pulmonary smooth
      muscle cell proliferation via the serotonin transporter (5-HTT). This study was
      designed to investigate expressions of 5-HT2A and 5-HTT in the pulmonary
      vasculature of rats with nitrofen-induced CDH. METHODS: Rats were exposed to
      nitrofen or vehicle on D9. Fetuses were sacrificed on D21 and divided into
      nitrofen and control group (n=32). Pulmonary RNA was extracted and mRNA level of
      5HT2A was determined by qRT-PCR. Protein expression of 5HT2A and 5-HTT was
      investigated by western blotting. Confocal immunofluorescence double-staining for
      5-HT2A, 5-HTT, and alpha smooth muscle actin were performed. RESULTS: Pulmonary 5
      HT2A gene expression levels were significantly increased in nitrofen-induced CDH
      compared to controls. Western blotting and confocal microscopy confirmed
      increased pulmonary protein expression in CDH lungs compared to controls.
      CONCLUSION: Increased gene and protein expression of 5HT2A and 5-HTT in the
      pulmonary vasculature of nitrofen-induced CDH lungs suggest that 5HT2A and 5-HTT
      are important mediators of PH in nitrofen-induced CDH.

PMID- 24888826
TI  - Prenatal retinoic acid increases lipofibroblast expression in hypoplastic rat
      lungs with experimental congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Prenatal administration of all-trans retinoic acid (ATRA) has
      been shown to stimulate alveolarization in nitrofen-induced pulmonary hypoplasia
      (PH) associated with congenital diaphragmatic hernia (CDH). Lipid-containing
      interstitial lipofibroblasts (LIFs), characterized by adipocyte differentiation
      related protein (ADRP), play a critical role in alveolar development by
      coordinating lipid homeostasis. Previous studies have demonstrated that ATRA
      positively affects LIF expression in developing lungs. We hypothesized that
      pulmonary LIF expression is increased after prenatal ATRA treatment in the
      nitrofen model of CDH-associated PH. METHODS: Timed-pregnant rats were treated
      with nitrofen or vehicle on E9.5, followed by injection of ATRA or placebo on
      E18.5, E19.5, and E20.5. Fetal lungs were dissected on E21.5 and divided into
      Control+Placebo, Control+ATRA, Nitrofen+Placebo, and Nitrofen+ATRA. Pulmonary
      gene expression levels of ADRP were analyzed by quantitative real-time polymerase
      chain reaction, and LIF expression was investigated by ADRP immunohistochemistry,
      oil-red-O-, and immunofluorescence-double-staining. RESULTS: Relative mRNA
      expression of pulmonary ADRP was significantly increased in Nitrofen+ATRA
      compared to Nitrofen+Placebo (0.31+/-0.02 vs. 0.08+/-0.01; P<0.0001). ADRP
      immunoreactivity and oil-red-O-staining were markedly increased in alveolar
      interstitium of Nitrofen+ATRA compared to Nitrofen+Placebo. Immunofluorescence
      double-staining confirmed markedly increased LIF expression in alveolar walls of
      Nitrofen+ATRA compared to Nitrofen+Placebo. CONCLUSIONS: Increased LIF expression
      after prenatal treatment with ATRA in nitrofen-induced PH suggests that ATRA may
      have a therapeutic potential in attenuating CDH-associated PH by stimulating
      alveolar development.

PMID- 24888828
TI  - Musculoskeletal deformities following repair of large congenital diaphragmatic
      hernias.
AB  - PURPOSE: Large congenital diaphragmatic hernias (CDH) can be repaired with either
      a muscle flap or prosthetic patch. The purpose of this study was to assess the
      frequency and severity of scoliosis, chest wall, and abdominal wall deformities
      following these repairs. METHODS: Neonates who underwent CDH repair (1989-2012)
      were retrospectively reviewed. We then validated our retrospective review by
      comparing results of a focused radiologic evaluation and clinical examination of
      patients with large defects seen in prospective follow-up clinic. Tests for
      association were made using Fisher's exact test. RESULTS: 236 patients survived
      at least 1year. Of these patients, 30 had a muscle flap, and 13 had a patch
      repair. Retrospectively, we identified pectus in 9% of primary repairs, 47% of
      flap repairs, and 54% of patch repairs. We identified scoliosis in 7% of primary
      repairs, 13% of flap repairs, and 15% of patch repairs. Prospectively, 75% of
      flap patients and 67% of patch patients had pectus and 13% of flap patients and
      33% of patch patients had scoliosis. There was no significant difference between
      flap and patch patients. CONCLUSIONS: Scoliosis and pectus deformity were common
      in children with large CDH. The operative technique did not appear to affect the
      incidence of subsequent skeletal deformity.

PMID- 24888827
TI  - Predictors of early lung function in patients with congenital diaphragmatic
      hernia.
AB  - PURPOSE: Long-term pulmonary outcomes of congenital diaphragmatic hernia (CDH)
      have demonstrated airflow obstruction in later childhood. We examined pulmonary
      function data to assess what factors predict lung function in the first three
      years of life in children with CDH. METHODS: This was a retrospective study of
      patients treated for CDH who underwent infant pulmonary function testing (IPFT)
      between 2006 and 2012. IPFT was performed using the raised volume rapid
      thoracoabdominal compression technique and plethysmography. RESULTS: Twenty-nine
      neonates with CDH had IPFTs in the first 3years of life. Their mean predicted
      survival using the CDH Study Group equation was 63%+/-4%. Fourteen infants (48%)
      required extracorporeal membrane oxygenation (ECMO). The mean age at IPFT was
      85.1+/-5weeks. Airflow obstruction was the most common abnormality, seen in 14
      subjects. 12 subjects had air trapping, and 9 demonstrated restrictive disease.
      ECMO (p=0.002), days on the ventilator (p=0.028), and days on oxygen (p=0.023)
      were associated with restrictive lung disease. CONCLUSION: Despite following a
      group of patients with severe CDH, lung function revealed mild deficits in the
      first three years of life. Clinical markers of increased severity (ECMO,
      ventilator days, and prolonged oxygen use) are correlated with reduced lung
      function.

PMID- 24888829
TI  - Incidence and factors associated with sensorineural and conductive hearing loss
      among survivors of congenital diaphragmatic hernia.
AB  - PURPOSE: The reported incidence of sensorineural hearing loss (SNHL) in long-term
      survivors of congenital diaphragmatic hernia varies widely in the literature.
      Conductive hearing loss (CHL) is also known to occur in CDH patients, but has
      been less widely studied. We sought to characterize the incidence and risk
      factors associated with SNHL and CHL in a large cohort of CDH patients who
      underwent standardized treatment and follow-up at a single institution. METHODS:
      We retrospectively reviewed charts of all CDH patients in our pulmonary
      hypoplasia program from January 2004 through December 2012. Categorical variables
      were analyzed by Fisher's exact test and continuous variables by Mann-Whitney t
      test (p<=0.05). RESULTS: A total of 112 patients met study inclusion criteria,
      with 3 (2.7%) patients diagnosed with SNHL and 38 (34.0%) diagnosed with CHL.
      SNHL was significantly associated with requirement for ECMO (p=0.0130), prolonged
      course of hospitalization (p=0.0011), duration of mechanical ventilation
      (p=0.0046), requirement for tracheostomy (p=0.0013), and duration of loop
      diuretic (p=0.0005) and aminoglycoside therapy (p=0.0003). CONCLUSIONS: We have
      identified hearing anomalies in over 30% of long-term CDH survivors. These
      findings illustrate the need for routine serial audiologic evaluations throughout
      childhood for all survivors of CDH and stress the importance of targeted
      interventions to optimize long-term developmental outcomes pertaining to speech
      and language.

PMID- 24888830
TI  - Sensorineural hearing loss in congenital diaphragmatic hernia survivors is
      associated with postnatal management and not defect size.
AB  - BACKGROUND/PURPOSE: We determined the incidence of sensorineural hearing loss
      (SNHL; >20dB at any frequency) in a contemporary cohort of congenital
      diaphragmatic hernia (CDH) survivors at a single tertiary care center and
      identified potential risk factors for SNHL. METHODS: From 2000 through 2011,
      clinical and audiologic data were collected on 122 surgically-repaired Bochdalek
      CDH patients. CDH defect size, duration of ventilation, and cumulative
      aminoglycoside treatment were used for multivariate logistic regression. RESULTS:
      Incidence of SNHL was 7.4% (9/122). We identified one significant independent
      predictor of SNHL: cumulative length of aminoglycoside treatment (P<.001; OR
      1.44, 95% CI: 1.13-1.83). CONCLUSIONS: Over the last decade, the incidence of
      SNHL in our CDH patients is low compared to previous reports in the literature
      (7.4%) and is not associated with CDH defect size or the need for extracorporeal
      membrane oxygenation. Prolonged duration of aminoglycoside treatment increases
      the risk of SNHL independent of defect size and duration of ventilation.

PMID- 24888831
TI  - Outcomes of fetal intervention for primary hydrothorax.
AB  - OBJECTIVE: Primary hydrothorax is a rare congenital anomaly with outcomes ranging
      from spontaneous resolution to fetal demise. We reviewed our experience with
      fetuses diagnosed with primary hydrothorax to evaluate prenatal management
      strategies. METHODS: We reviewed the records of patients evaluated for fetal
      pleural effusions at our Fetal Treatment Center between 1996 and 2013. To define
      fetuses with primary hydrothorax, we excluded those with structural or genetic
      anomalies, diffuse lymphangiectasia, immune hydrops, and monochorionic diamniotic
      twin gestations. RESULTS: We identified 31 fetuses with primary hydrothorax, of
      whom 24 had hydrops. Hydropic fetuses were more likely to present with bilateral
      effusions. Of all fetuses with primary hydrothorax, 21 had fetal interventions.
      Survival without hydrops was 7/7 (100%), whereas survival with hydrops depended
      on whether or not the patient had fetal intervention: 12/19 (63%) with
      intervention and 1/5 (20%) without intervention. Premature delivery was common
      (44%) among those who had fetal intervention. CONCLUSIONS: Fetal intervention for
      primary hydrothorax may lead to resolution of hydrops, but preterm birth and
      neonatal demise still occur. Understanding the pathophysiology of hydrops may
      provide insights into further prenatal management strategies, including targeted
      therapies to prevent preterm labor.

PMID- 24888832
TI  - Segmental resection for the treatment of congenital pulmonary malformations.
AB  - PURPOSE: The purpose of this study was to compare clinical outcomes of segmental
      resection to lobectomy as increasing antenatal diagnosis of congenital pulmonary
      malformations has led to a shift in surgical management. METHODS: A retrospective
      institutional review for patients undergoing surgical excision of congenital
      pulmonary malformations was performed. RESULTS: Sixty-two patients with
      congenital pulmonary malformations were reviewed between 2001 and 2012. Forty
      five were included for analysis. Malformations were subdivided into two groups,
      including congenital lobar emphysema (CLE) (n=11, 24%) and intrapulmonary (IP)
      lesions (n=34, 76%). Nineteen (56%) IP patients underwent segmental resection,
      and 15 (79%) were performed thoracoscopically without conversion to thoracotomy.
      None of these patients had recurrent disease. Lobectomy was performed in 11
      (100%) CLE and 15 (44%) IP patients, and the majority were by thoracotomy. Median
      hospital stay was longer for the lobectomy group at 7days when compared to the
      segmentectomy group at 2days (p<0.001). There was not a difference in
      complication rate (21% vs. 19%, p=1.000) or in median number of chest tube days
      (2 vs. 3days, p=0.079) for segmentectomy versus lobectomy patients. CONCLUSIONS:
      Segmental resections of congenital pulmonary malformations can be performed
      safely while conserving healthy lung tissue.

PMID- 24888833
TI  - Slide tracheoplasty for the treatment of tracheoesophogeal fistulas.
AB  - PURPOSE: The purpose of this study is to determine the surgical outcome of slide
      tracheoplasty for the treatment of tracheoesophageal (TE) fistula in pediatric
      patients. METHODS: After internal review board approval, the charts of pediatric
      patients (0-18years old) who had undergone slide tracheoplasty for
      tracheoesophageal fistula were retrospectively reviewed. Patient information and
      surgical outcomes were reviewed. RESULTS: Nine patients underwent slide
      tracheoplasty for correction of TE fistula. In five patients the original TE
      fistula was congenital. Other causes included battery ingestion, tracheostomy
      tube complications, foreign body erosion, and an iatrogenic injury. The average
      age at repair was 48+/-64 months (range: 1-190). Seven patients had undergone
      previous TEF repair either open or endoscopically. There were no recurrences
      after repair. Two patients had sternal periosteum interposed between the
      esophagus and trachea. There were no TEF recurrences. A single patient had
      dehiscence of the tracheal anastomosis and underwent a second procedure.
      CONCLUSION: Slide tracheoplasty is an effective method to treat complex TE
      fistulas. The procedure was not associated with any recurrences. This is the
      first description of a novel, effective, and safe method to treat TE fistulas.

PMID- 24888835
TI  - Postoperative opioid analgesic use after Nuss versus Ravitch pectus excavatum
      repair.
AB  - BACKGROUND/PURPOSE: Anticipated postoperative pain may affect procedure choice in
      patients with pectus excavatum. This study aims to compare postoperative pain in
      patients undergoing Nuss and Ravitch procedures. METHODS: A 5year retrospective
      review was performed. Data on age, gender, Haller index, procedure, pain scores,
      pain medications, and length of hospital stay were collected. Total inpatient
      opioid administration was converted to morphine equivalent daily dose per
      kilogram (MEDD/kg) and compared between procedures. RESULTS: One hundred eighty
      one patients underwent 125 (69%) Nuss and 56 (31%) Ravitch procedures. Ravitch
      patients were older (15.7 yo vs 14.6 yo, p=0.004) and had a higher Haller index
      (5.21 vs 4.10, p=<0.001). Nuss patients had higher average daily pain scores,
      received 25% more opioids (MEDD/kg 0.66 vs. 0.49, p=<0.001), and received twice
      as much IV diazepam/kg. In the multivariate analysis, higher MEDD/kg correlated
      with both the Nuss procedure and older age in the Nuss group. Opioid
      administration did not correlate with Haller index or Nuss bar fixation
      technique. Increased NSAID administration did not correlate with lower use of
      opioids. CONCLUSION: The Nuss procedure is associated with greater postoperative
      pain compared to the Ravitch procedure. Opioid use is higher in older patients
      undergoing the Nuss procedure, but is not associated with severity of deformity.

PMID- 24888834
TI  - A comparative analysis of human mesenchymal stem cell response to hypoxia in
      vitro: Implications to translational strategies.
AB  - PURPOSE: Mesenchymal stem cells (MSCs) are particularly valuable for structural
      tissue replacement. We compared the response to hypoxia among human MSCs derived
      from four different clinically relevant sources as an adjunct to translational
      developments. METHODS: Immunophenotypically indistinguishable human MSC lineages
      derived from bone marrow (bmMSCs), adipose tissue (adMSCs), amniotic fluid
      (afMSCs), and umbilical cord blood (cbMSCs) were submitted to either room air or
      1% O2, under otherwise standard culture conditions. Cell expansion and
      quantitative RT-PCR data were obtained at different time points. Statistical
      analysis was by two-way mixed model and the F-test (P<0.05). RESULTS: The effect
      of hypoxia on expansion kinetics was dependent on cell source. Only prenatal
      sources of MSCs - afMSCs (P=0.002) and cbMSCs (P<0.001) - proliferated
      significantly faster under hypoxia than normoxia. Increased HIF1-alpha expression
      correlated consistently with increased cell expansion only among afMSCs. There
      were no significant variabilities in Survivin, Oct-4, and VEGF expressions.
      CONCLUSIONS: Mesenchymal stem cell tolerance to hypoxia in vitro varies with cell
      source. Prenatal cells, particularly those derived from amniotic fluid, are more
      robust than their postnatal counterparts. HIF1-alpha may play a role in the
      amniotic fluid-derived cells' enhanced response. These findings should inform the
      choice of mesenchymal stem cells for prospective regenerative strategies.

PMID- 24888836
TI  - Evaluation of the treatment of pectus carinatum with compressive orthotic bracing
      using three dimensional body scans.
AB  - PURPOSE: The purpose of this study is to measure the effectiveness of compressive
      orthotic brace therapy for the treatment of pectus carinatum using an adjusted
      Haller Index (HI) measurement calculated from 3D body scan (BS) images. METHODS:
      Pediatric patients with pectus carinatum were treated with either compressive
      orthotic bracing or observation. An adjusted BS Haller index (HI) was calculated
      from serial 3D BS images obtained on all patients. Medical records were evaluated
      to determine treatment with bracing and brace compliance more than 12hours daily.
      Compliant patient measurements were compared to non-compliant and non-brace
      groups. RESULTS: Forty patients underwent compressive orthotic bracing, while ten
      were observed. Twenty-three patients were compliant with bracing, and seventeen
      patients were non-compliant. Compliant patients exhibited an 8.2% increase, non
      compliant patients had a 1.5% increase, and non-brace patients exhibited a 2.5%
      increase in BS HI. The change in BS HI of compliant patients was significantly
      different compared to non-brace patients (p=0.004) and non-compliant patients
      (p<0.001). CONCLUSIONS: Three dimensional BS is an effective, radiation free, and
      objective means to evaluate patients treated with compressive orthotic bracing.

PMID- 24888837
TI  - Is early delivery beneficial in gastroschisis?
AB  - PURPOSE: Gastroschisis neonates have delayed time to full enteral feeds (ENT),
      possibly due to bowel exposure to amniotic fluid. We investigated whether
      delivery at <37weeks improves neonatal outcomes of gastroschisis and impact of
      intra/extra-abdominal bowel dilatation (IABD/EABD). METHODS: A retrospective
      review of gastroschisis (1992-2012) linked fetal/neonatal data at 2 tertiary
      referral centers was performed. Primary outcomes were ENT and length of hospital
      stay (LOS). Data (median [range]) were analyzed using parametric/non-parametric
      tests, positive/negative predictive values, and regression analysis. RESULTS: Two
      hundred forty-six patients were included. Thirty-two were complex
      (atresia/necrosis/perforation/stenosis). ENT (p<0.0001) and LOS (p<0.0001) were
      reduced with increasing gestational age. IABD persisted to last scan in 92
      patients, 68 (74%) simple (intact/uncompromised bowel), 24 (26%) complex. IABD or
      EABD diameter in complex patients was not significantly greater than simple
      gastroschisis. Combined IABD/EABD was present in 22 patients (14 simple, 8
      complex). When present at <30weeks, the positive predictive value for complex
      gastroschisis was 75%. Two patients with necrosis and one atresia had IABD and
      collapsed extra-abdominal bowel from <30weeks. CONCLUSION: Early delivery is
      associated with prolonged ENT/LOS, suggesting elective delivery at <37weeks is
      not beneficial. Combined IABD/EABD or IABD/collapsed extra-abdominal bowel is
      suggestive of complex gastroschisis.

PMID- 24888838
TI  - Heterotaxy syndrome and malrotation: does isomerism influence risk and decision
      to treat.
AB  - PURPOSE: Controversy remains regarding the management of the asymptomatic
      heterotaxy syndrome (HS) patient with suspected intestinal rotational
      abnormalities. We evaluated the outcomes for our HS population to identify
      frequency of malrotation and identify characteristics of children who might
      benefit from expectant management. METHODS: After IRB approval, a retrospective
      review of all patients treated for HS at a large tertiary care children's
      hospital between January 2008 and June 2012 was performed. For the purpose of
      this paper, malrotation was defined as an operative note that described the
      presence of Ladd's bands and a narrow mesentery. RESULTS: Thirty-eight patients
      with HS were identified, including 18 who underwent abdominal exploration. Left
      atrial isomerisation (LAI) was identified in 13 individuals, and right atrial
      isomerisation (RAI) was noted in 25. The rate of surgical intervention did not
      vary between the 2 groups (54%). Malrotation was found in 8 patients: one with
      LAI and 7 with RAI. This difference in incidence was statistically significant
      (p=0.04). CONCLUSION: These data suggest that the direction of atrial
      isomerisation influences the likelihood of true malrotation, where RAI patients
      are more likely to be malrotated. Given the inherent risk of surgery on this
      medically fragile patient population, surgeons should consider expectant
      management for asymptomatic LAI patients.

PMID- 24888840
TI  - Application of prostaglandin E2 improves ileal blood flow in NEC.
AB  - PURPOSE: Indomethacin, a nonselective prostaglandin inhibitor used to treat
      patent ductus arteriosus, is associated with intestinal perforation inducing an
      NEC-like illness. We sought to define the contribution of prostaglandin E2 (PG
      E2) and its receptor EP4 to intestinal blood flow regulation in premature
      neonates with NEC. METHODS: Newborn Sprague-Dawley rats were randomized by litter
      to undergo experimental NEC induction or to serve as a CONTROL. At 48hours of
      age, intestinal laser Doppler blood flow was assessed at baseline and after
      intraperitoneal administration of indomethacin, PG E2, EP4 antagonist, or EP4
      agonist. Data were analyzed using a 2-way ANOVA with post hoc Tukey-Kramer
      correction. RESULTS: At baseline, NEC animals had lower intestinal blood flow
      than controls. Indomethacin, PG E2 and EP4 agonist all increased ileal blood
      flow, but PG E2 and EP4 agonist increased blood flow the most in NEC pups. EP4
      antagonist decreased intestinal perfusion in both groups. CONCLUSION: The above
      evidence suggests the importance of PG E2 and EP4 in regulation of neonatal
      intestinal blood flow. Since indomethacin treatment of patent ductus arteriosus
      in the premature infant is associated with an increased risk of intestinal
      perforation owing to compromised blood flow, PG E2 supplementation might provide
      intestinal protection if administered simultaneously with indomethacin.

PMID- 24888841
TI  - Late onset of necrotizing enterocolitis in the full-term infant is associated
      with increased mortality: results from a two-center analysis.
AB  - PURPOSE: The effect of timing of onset of necrotizing enterocolitis (NEC) on
      outcomes has not been determined for the full-term infant. In this study we aimed
      to characterize the full-term NEC population and to evaluate onset of NEC.
      METHODS: We performed a two-center retrospective review of all full-term infants
      (>= 37weeks) with a diagnosis of NEC between 1990 and 2012. Patients were
      identified by ICD-9 and age. Early onset for NEC was <=7days and late onset after
      7days of life. Demographics, comorbidities, maternal factors, clinical factors,
      surgical intervention, complications, and mortality were evaluated. Wilcoxon's
      test was performed on continuous variables and Fisher's exact test on categorical
      data. A p-value<0.05 was considered significant. Univariate outcomes with a p
      value<0.1 were selected for multivariable analysis. RESULTS: Thirty-nine patients
      (24 boys, 15 girls) with median EGA of 39weeks were identified. Overall mortality
      was 18%. Univariate predictors of mortality included congenital heart disease and
      placement of an umbilical artery (UA) catheter. Multivariate analysis revealed
      late onset of NEC to be an independent predictor of mortality (OR 90.8, 95% CI
      2.6-3121). CONCLUSION: Full-term infants who develop NEC after 7days of life,
      have congenital heart disease, and/or need UA catheterization have increased
      mortality.

PMID- 24888839
TI  - HB-EGF augments the ability of mesenchymal stem cells to attenuate intestinal
      injury.
AB  - BACKGROUND: We have previously demonstrated that heparin-binding EGF-like growth
      factor (HB-EGF) and mesenchymal stem cell (MSC) administration protect the
      intestines from ischemia/reperfusion (I/R) injury in vivo, with amniotic fluid
      derived MSC (AF-MSC) being more efficacious than bone marrow-derived MSC (BM
      MSC). The goal of the current study was to determine whether the protective
      effects of HB-EGF were from direct effects on MSC or via alternative mechanisms.
      METHODS: Murine MSC were transfected with an HB-EGF plasmid or control plasmid by
      electroporation. Mice were subjected to segmental intestinal I/R injury and
      received either BM-MSC or AF-MSC either with or without exogenous HB-EGF, or BM
      MSC or AF-MSC that endogenously over-expressed HB-EGF. MSC engraftment,
      intestinal histologic injury, and intestinal permeability were quantified.
      RESULTS: There was increased MSC engraftment into injured compared to uninjured
      intestine. HB-EGF increased AF-MSC engraftment into injured intestine.
      Administration of HB-EGF and MSC improved intestinal histology and intestinal
      permeability after I/R injury, with AF-MSC being most efficacious. The effect of
      HB-EGF on MSC was similar when the growth factor was administered exogenously, or
      when it was overexpressed endogenously. CONCLUSIONS: The effect of HB-EGF on AF
      MSC was similar with both exogenous administration and endogenous overexpression
      of the growth factor, implying that HB-EGF has a direct effect on AF-MSC. This
      information may assist in guiding potential future AF-MSC-based therapies for
      patients at risk of intestinal ischemic injuries.

PMID- 24888843
TI  - Oral relaxin maintains intestinal blood flow in a rat model of NEC.
AB  - PURPOSE: Intestinal vasoconstriction is a critical step in development of
      necrotizing enterocolitis (NEC). Relaxin (RLXN), a hormone found in breast milk
      but absent from formula, is a potent vasodilator. We hypothesized that relaxin
      supplemented feeds with an NEC protocol would decrease NEC severity and increase
      intestinal blood flow. METHODS: Timed-pregnant Sprague-Dawley rats were randomly
      assigned to CONTROL, NEC, NEC+1xRLXN, or NEC+All Feeds RLXN, and all but CONTROL
      underwent NEC protocol. NEC+1xRLXN and NEC+All Feeds RLXN groups were fed relaxin
      supplemented formula with the last feed or every feed. At 48h of life, intestinal
      blood flow was measured at baseline and after application of 2.5% Delflex(r)
      solution. RESULTS: The addition of relaxin to NEC group feeds (1x or All Feeds)
      improved the degree of ileal injury. Ileal blood flow was decreased in the NEC
      pups compared to the CONTROLS, but the addition of relaxin to one feed increased
      baseline ileal blood flow in the NEC group compared to NEC alone. Furthermore,
      the addition of relaxin to ALL feeds significantly increased baseline ileal blood
      flow. CONCLUSION: Pups who received relaxin with all feeds had substantially
      increased ileal perfusion compared to control pups. Our data suggest that relaxin
      supplementation maintains intestinal blood flow and results in less histologic
      NEC.

PMID- 24888842
TI  - Intestinal alkaline phosphatase is protective to the preterm rat pup intestine.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most common surgical emergency
      in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing
      enterocolitis is highly variable and associated with numerous risk factors. Prior
      research has shown that enteral supplementation with intestinal alkaline
      phosphatase (IAP) decreases the severity of NEC. The aim of this study is to
      investigate whether IAP is protective to the preterm intestine in the presence of
      formula feeding and in the absence of NEC. METHODS: Preterm rat pups were fed
      formula with or without supplementation with IAP, and intestine was obtained on
      day of life 3 for analysis of IAP activity, mRNA expression of TNFalpha, IL-6 and
      iNOS and permeability and cytokine expression after LPS exposure. RESULTS: There
      was no difference in the absolute and intestine specific alkaline phosphatase
      activity in both groups. Rat pups fed IAP had decreased mRNA expression of the
      inflammatory cytokines TNFalpha, IL-6 and iNOS. Pups supplemented with IAP had
      decreased permeability and inflammatory cytokine expression after exposure to LPS
      ex vivo when compared to formula fed controls. CONCLUSIONS: Our results support
      that IAP is beneficial to preterm intestine and decreases intestinal injury and
      inflammation caused by LPS.

PMID- 24888845
TI  - Function of mechanically lengthened jejunum after restoration into continuity.
AB  - PURPOSE: Distraction enterogenesis is a potential treatment for patients with
      short bowel syndrome. We previously demonstrated successful lengthening of
      jejunum using a degradable spring device in rats. Absorptive function of the
      lengthened jejunum after restoration into intestinal continuity needs to be
      determined. METHODS: Encapsulated polycaprolactone springs were placed into
      isolated jejunal segments in rats for four weeks. Lengthened segments of jejunum
      were subsequently restored into intestinal continuity. Absorption studies were
      performed by placing a mixture of a non-absorbable substrate and glucose into the
      lumen of the restored jejunum. RESULTS: Restored jejunal segments demonstrated
      visible peristalsis at specimen retrieval. Compared to normal jejunal controls,
      restored segments demonstrated equal water absorption and greater glucose
      absorption. Restored segments had thicker smooth muscle, increased villus height,
      increased crypt depth, and decreased sucrase activity compared to normal jejunum.
      The density of enteric ganglia increased after restoration to near normal levels
      in the submucosa and to normal levels in the myenteric plexus. CONCLUSION:
      Jejunum lengthened with a degradable device demonstrates peristaltic and
      enzymatic activity as well as glucose and water absorption after restoration into
      intestinal continuity. Our findings further demonstrate the therapeutic potential
      of a degradable device.

PMID- 24888844
TI  - Insulin-like growth factor 2 and its enterocyte receptor are not required for
      adaptation in response to massive small bowel resection.
AB  - PURPOSE: Enhanced structural features of resection-induced intestinal adaptation
      have been demonstrated following the administration of multiple different growth
      factors and peptides. Among these, the insulin-like growth factor (IGF) system
      has been considered to be significant. In this study, we employ mutant mouse
      strains to directly test the contribution of IGF2 and its enterocyte receptor
      (IGF1R) toward the adaptation response to massive small bowel resection (SBR).
      METHODS: IGF2-knockout (IGF2-KO) (n=8) and intestine specific IGF1R-knockout mice
      (IGF1R-IKO) (n=9) and their wild type (WT) littermates (n=5, n=7, respectively)
      underwent 50% proximal SBR. At post-operative day 7, structural adaptation was
      measured as crypt depth and villus height. Rates of enterocyte proliferation and
      apoptosis were also recorded. RESULTS: The successful deletion of IGF2 and IGF1R
      expression in the enterocytes was confirmed by RT-PCR and Western blot,
      respectively. Normal adaptation occurred in both IGF2-KO and IGF1R-IKO mice after
      50% SBR. Post-operative rates of proliferation and apoptosis in both IGF2-KO and
      IGF1R-IKO mice were no different than their respective controls. CONCLUSION: IGF2
      and functional IGF1R signaling in enterocytes are both dispensable for resection
      induced adaptation responses. The mechanism for IGF-stimulation of intestinal
      adaptation may involve other ligands or cellular compartments within the
      intestine.

PMID- 24888847
TI  - Glycolysis inhibition and its effect in doxorubicin resistance in neuroblastoma.
AB  - BACKGROUND/PURPOSE: A common trait among cancers is the increased level of
      glycolysis despite adequate oxygen levels to support aerobic respiration. This
      has been shown repeatedly in different human malignancies. Glycolysis inhibitors,
      especially 3-bromopyruvate, have been shown to be effective chemotherapeutic
      agents. The effect of glycolysis inhibition upon chemotherapy resistance is
      relatively unknown. METHODS: Wild-type and doxorubicin-resistant lines of
      neuroblastoma (SK-N-SH and SK-N-Be(2)C) were used in this study. Using an MTT
      assay, the IC50 of 3-BrPA was determined. Subsequently, doxorubicin-resistant
      cell lines were treated with 3-bromopyruvate, doxorubicin, and 3-bromopyruvate
      with doxorubicin. Additionally, a luminescence ATP detection assay was used to
      measure intracellular ATP levels, and a lactate assay was used to determine
      intracellular lactate levels. All experiments were repeated in hypoxic
      conditions. RESULTS: Treatment with 3-bromopyruvate and doxorubicin significantly
      decreased the mean cell viabilities at 24, 48, and 72hours in normoxic
      conditions. A similar response was replicated in hypoxic conditions. Treatment
      with 3-bromopyruvate significantly decreased intracellular ATP and lactate
      levels. CONCLUSION: Glycolysis inhibitors such as 3-bromopyruvate could prove to
      become an effective means by which chemotherapy resistance can be overcome in
      human neuroblastoma.

PMID- 24888848
TI  - Sacrococcygeal teratoma growth rate predicts adverse outcomes.
AB  - PURPOSE: The purpose of this study was to characterize the growth rate of
      sacrococcygeal teratomas (SCTs) and determine its relationship to adverse
      outcomes. METHODS: A retrospective review of all pathology-confirmed isolated SCT
      patients evaluated with at least two documented ultrasounds and followed through
      hospital discharge between 2005 and 2012 was conducted. SCT growth rate was
      calculated as the difference between tumor volumes on a late- and early-gestation
      ultrasound divided by the difference in time. Outcomes were death, high-output
      cardiac failure (HOCF), hydrops, and preterm delivery. Student's t-test, receiver
      operator characteristics, Fisher's Exact test, and Pearson's correlation were
      performed. RESULTS: Of the 28 study subjects, there were 3 in utero demises and 2
      neonatal deaths. Significantly faster SCT growth rates were seen in all adverse
      outcomes, including death (p<0.0001), HOCF (p=0.005), and preterm delivery
      (p=0.009). There was a significant association with adverse outcomes at
      >61cm(3)/week (AUC=0.87, p=0.001, LR=4.52). Furthermore, there was an even
      greater association with death at >165cm(3)/week (AUC=0.93, p=0.003, LR=18.42).
      Growth rate was directly correlated with the percent of solid tumor (r=0.60,
      p=0.0008). CONCLUSION: Faster SCT growth is associated with adverse outcomes. SCT
      growth rate determined by ultrasound is an effective prognostic indicator for
      adverse outcomes and easily applied to patient management.

PMID- 24888846
TI  - CXCL5 is required for angiogenesis, but not structural adaptation after small
      bowel resection.
AB  - PURPOSE: Intestinal adaptation is the compensatory response to massive small
      bowel resection (SBR) and characterized by lengthening of villi and deepening of
      crypts, resulting in increased mucosal surface area. Previous studies have
      demonstrated increased villus capillary blood vessel density after SBR,
      suggesting a role for angiogenesis in the development of resection-induced
      adaptation. Since we have previously shown enhanced expression of the
      proangiogenic chemokine CXCL5 after SBR, the purpose of this study was to
      determine the effect of disrupted CXCL5 expression on intestinal adaptation.
      METHODS: CXCL5 knockout (KO) and C57BL/6 wild type (WT) mice were subjected to
      either a 50% proximal SBR or sham operation. Ileal tissue was harvested on
      postoperative day 7. To assess for adaptation, villus height and crypt depth were
      measured. Submucosal capillary density was measured by CD31 immunohistochemistry.
      RESULTS: Both CXCL5-KO and WT mice demonstrated normal structural features of
      adaptation. Submucosal capillary density increased in the WT but not in the KO
      mice following SBR. CONCLUSION: CXCL5 is required for increased intestinal
      angiogenesis during resection-induced adaptation. Since adaptive villus growth
      occurs despite impaired CXCL5 expression and enhanced angiogenesis, this suggests
      that the growth of new blood vessels is not needed for resection-induced mucosal
      surface area expansion following massive SBR.

PMID- 24888849
TI  - Management of neonatal ovarian cysts and its effect on ovarian preservation.
AB  - BACKGROUND/PURPOSE: Management of asymptomatic neonatal ovarian cysts varies.
      Some surgeons advocate initial observation, while others recommend immediate
      operation depending on cyst size and complexity. This study aims to compare
      outcomes of initial observation versus primary surgery, focusing on incidence of
      postnatal torsion and ovarian preservation. METHODS: A retrospective study (1997
      2012) of neonates with an ovarian mass was performed. Data on cyst size,
      ultrasound characteristics, clinical course, complications, and pathology were
      extracted. RESULTS: Thirty-seven neonates with asymptomatic ovarian cysts were
      identified (N=25 observed, N=12 primary surgery). Overall, 12/25 (48%) observed
      had successful cyst regression, including 3/8 (38%) cysts >=50mm and 6/15 (40%)
      complex. 13/25 patients (52%) underwent surgery for failure of cyst regression
      (11/13) or concern for interval torsion (2/13). Postnatal torsion occurred in
      1/25 observation patients (4%), or 1/8 (13%) with cysts>=50mm. Overall rate of
      ovarian preservation between groups was not statistically different [6/8 (75%)
      observed versus 8/9 (89%) primary surgery; P=0.577]. Pathology found viable
      ovarian tissue in all oophorectomy specimens (N=3). CONCLUSIONS: Postnatal
      torsion is rare. A period of observation spares half of neonates from an
      operation, without decreasing ovarian salvage. Initial management should consist
      of observation, regardless of size or complex characteristics. If operative
      intervention is necessary, ovary preserving techniques should be utilized.

PMID- 24888850
TI  - Age at presentation of common pediatric surgical conditions: Reexamining dogma.
AB  - PURPOSE: The commonly cited ages at presentation of many pediatric conditions
      have been based largely on single center or outdated epidemiologic evidence.
      Thus, we sought to examine the ages at presentation of common pediatric surgical
      conditions using cases from large national databases. METHODS: A retrospective
      analysis was performed on Healthcare Cost and Utilization Project databases from
      1988 to 2009. Pediatric discharges were selected using matched ICD9 diagnosis and
      procedure codes for malrotation, intussusception, hypertrophic pyloric stenosis
      (HPS), incarcerated inguinal hernia (IH), and Hirschsprung disease (HD).
      Descriptive statistics were computed. RESULTS: A total of 63,750 discharges were
      identified, comprising 2744 cases of malrotation, 5831 of intussusception, 36,499
      of HPS, 8564 of IH, and 10,112 of HD. About 58.2% of malrotation cases presented
      before age 1. Moreover, 92.8% of HPS presented between 3 and 10weeks. For
      intussusception, 50.3% and 91.4% presented prior to ages 1 and 4years,
      respectively. Also, 55.8% of IHD cases presented before their first birthday. For
      HD, 6.5% of cases presented within the neonatal period and 45.9% prior to age
      1year. CONCLUSION: Our findings support generally cited presenting ages for HPS
      and intussusception. However, the ages at presentation for HD, malrotation, and
      IH differ from commonly cited texts.

PMID- 24888851
TI  - Racial/ethnic and socioeconomic disparities in the use of helmets in children
      involved in bicycle accidents.
AB  - PURPOSE: While bicycle helmet use reduces bicycle-related head injury, few
      children wear them regularly. We aimed to describe racial/ethnic and
      socioeconomic differences in pediatric helmet use in Los Angeles County (LAC) to
      help target groups for injury prevention programs. METHODS: A retrospective
      review of all pediatric patients involved in bicycle-related accidents in LAC
      between 2006 and 2011 was performed. Our primary analysis examined the
      association between helmet use and age, gender, insurance status, and
      race/ethnicity. We also evaluated the association between helmet use and the need
      for emergency surgery, mortality, and length of hospital stay (LOH), after
      adjusting for injury severity score (ISS), age, insurance status, and
      race/ethnicity. RESULTS: Of 1248 patients, 11.3% wore helmets, with decreased use
      among children 12years and older, minorities, and those without private
      insurance. Overall, 5.9% required an emergency operation, 34.1% returned to their
      pre-injury capacity, and mortality was 0.7%. On multivariable analysis, higher
      ISS increased LOH, the risk for emergency surgery, and mortality. CONCLUSION:
      Nearly 90% of children involved in bicycle-related accidents were not wearing
      helmets. Helmet use was lower among older children, minorities, and those from a
      low socioeconomic status. Injury prevention programs targeting low-income middle
      and high schools and minority communities may help increase helmet use in
      children in LAC.

PMID- 24888852
TI  - National trends in pediatric blunt spleen and liver injury management and
      potential benefits of an abbreviated bed rest protocol.
AB  - PURPOSE: Recent reports suggest that an abbreviated bed rest protocol (ABRP) may
      safely reduce length of stay (LOS) and resource utilization in pediatric blunt
      spleen and liver injury (BSLI) patients. This study evaluates national temporal
      trends in BLSI management and estimates national reduction in LOS using an ABRP.
      METHODS: Pediatric patients (<18 years old) sustaining BLSI were identified in
      the Kids' Inpatient Database from 2000 to 2009. Yearly rates of injury and
      operative intervention were examined and stratified by type of injury. APSA
      guidelines and the reported ABRP were applied based on abbreviated injury score
      (AIS) and compared with actual LOS. RESULTS: 22,153 patients were identified.
      Over the study period, operative rates for spleen and liver injuries and overall
      mortality significantly declined: LOS=3.1 days (+/-1.6) and 2.7 days (+/-1.9) for
      spleen and liver, respectively. If APSA guidelines were followed, the rates were
      LOS=3.7 days (+/-1.1) and 3.4 days (+/-0.7), respectively. Application of the
      ABRP would result in LOS=1.3 days (+/-0.5) for all BSLI patients. An ABRP could
      potentially save 1.7 hospital days/patient or 36,964 patient hospital days
      nationally. CONCLUSION: Our study confirms a significant national decrease in
      operative intervention and overall mortality in patients with BSLI. Additionally,
      it appears that a shorter observation period than the APSA guidelines is being
      utilized. The implementation of ABRP holds potential in further reducing LOS and
      resource utilization.

PMID- 24888853
TI  - Management of pediatric snake bites: are we doing too much?
AB  - BACKGROUND: The optimal management of children with snake bite injuries is not
      well defined. The purpose of this study was to review the use of antivenom,
      diagnostic tests, and antibiotics in children bitten by venomous snakes in a
      specific geographic region (Southeast Texas). METHODS: This is a retrospective
      single-center review of all patients with snake bite injury from 1/2006 to
      6/2012. An envenomated bite was defined as causing edema, discoloration of the
      skin, necrosis, or systemic effects. The severity of injury was scored using a
      novel 4-point scale based on initial physical examination alone. RESULTS: One
      hundred fifty-one children (mean age 8.4+/-4.3years) were treated for a snake
      bite. There were no mortalities. Lower extremity injuries were most common (60%).
      Most bites were from copperheads (43%). Envenomation was evident in 82% (average
      wound score: 2.61+/-0.81). The median hospital stay for admitted patients (79%)
      was 2days (range 1-7). Four patients required surgery for complications of the
      snake bite. Fifty-two children (34%) received CroFab, with one allergic reaction.
      22/135 (16%) had evidence of coagulopathy. Seventy-two children (48%) received IV
      antibiotics. CONCLUSION: Despite a high rate of envenomated bites in Southeast
      Texas, significant morbidity is rare. Children with an envenomation score of 1 or
      2 are unlikely to be coagulopathic, suggesting that laboratory investigation
      should be reserved for patients with higher scores. The indications for the
      administration of CroFab deserve further prospective study.

PMID- 24888854
TI  - Radiation exposure - how do CT scans for appendicitis compare between a free
      standing children's hospital and non-dedicated pediatric facilities?
AB  - BACKGROUND: We compare the amount of radiation children receive from CT scans
      performed at non-dedicated pediatric facilities (OH) versus those at a dedicated
      children's hospital (CH). METHODS: Using a retrospective chart review, all
      children undergoing CT scanning for appendicitis at an OH were compared to
      children undergoing CT imaging for appendicitis at a CH between January 2011 and
      November 2012. RESULTS: One hundred sixty-three children underwent CT scans at 42
      different OH. Body mass index was similar between the two groups (21.00+/
      6.49kg/m(2), 19.58+/-5.18kg/m(2), P=0.07). Dose length product (DLP) was 620+/
      540.3 at OH and 253.78+/-211.08 at CH (P < 0.001). OH CT scans accurately
      diagnosed appendicitis in 81%, while CT scans at CH were accurate in 95%
      (P=0.026). CTDIvol was recorded in 65 patients with subset analysis showing
      CTDIvol of 16.98+/-15.58 and 4.89+/-2.64, a DLP of 586.25+/-521.59 and 143.54+/
      41.19, and size-specific dose estimate (SSDE) of 26.71+/-23.1 and 3.81+/-2.02 at
      OH and CH, respectively (P<0.001). CONCLUSION: Using SSDE as a marker for
      radiation exposure, children received 86% less radiation and had improved
      diagnostic accuracy when CT scans are performed at a CH.

PMID- 24888855
TI  - Standardization and improvement of care for pediatric patients with perforated
      appendicitis.
AB  - BACKGROUND/PURPOSE: Reduction of treatment variation and application of evidenced
      based care are increasingly important in the current care environment. Utilizing
      formal quality improvement methods, an evidenced based guideline was implemented
      at our institution. METHODS: A guideline was established regarding timing of
      surgery (immediate vs interval appendectomy) and duration of antibiotics. Twelve
      months of baseline data were collected prior to implementation. The guideline
      dictates immediate appendectomy (IA) and postoperative antibiotic therapy until
      discharge (regular diet, clinically improved, normal complete blood count (CBC)).
      Data was collected prospectively during hospitalization and at 30days
      postdischarge. Control charts document adherence to the overall guideline, IA,
      antibiotic guideline, and readmission for complications. RESULTS: Guideline
      implementation resulted in an increase in IA (79% vs 94%), decrease in the use of
      IV antibiotics post discharge (25% to 4%), no change in overall LOS, no change in
      postoperative abscess formation, and slight decrease in 30day readmission.
      Charges were decreased. CONCLUSION: Implementation of an evidenced based
      guideline resulted in significant practice change for managing perforated
      appendicitis. The changes suggest more efficient care without compromising
      patient outcome. Utilization of quality improvement methods allows for
      implementing and tracking the change as well as creating a platform for future
      improvement.

PMID- 24888856
TI  - Does delay in appendectomy affect surgical site infection in children with
      appendicitis?
AB  - PURPOSE: The purpose of this study was to investigate the association between
      time from diagnosis to operation and surgical site infection (SSI) in children
      undergoing appendectomy. METHODS: Pediatric patients undergoing appendectomy in
      2010-2012 were included. We collected data on patient demographics; length of
      symptoms; times of presentation, admission and surgery; antibiotic
      administration; operative findings; and occurrence of SSI. RESULTS: 1388 patients
      were analyzed. SSI occurred in 5.1% of all patients, 1.4% of simple appendicitis
      (SA) patients, and 12.4% of complex appendicitis (CA) patients. SSI did not
      increase significantly as the length of time between ED triage and operation
      increased (all patients, p=0.51; SA patients, p=0.91; CA patients, p=0.44) or
      with increased time from admission to operation (all patients, p=0.997; SA
      patients, p=0.69; CA patients, p=0.96). However, greater length of symptoms was
      associated with an increased risk of SSI (p<0.05 for all, SA and CA patients). In
      univariable analysis, obesity, and increased admission WBC count were each
      associated with significantly increased SSI. In multivariable analysis, only CA
      was a significant risk factor for SSI (p<0.0001). CONCLUSION: We found no
      significant increase in the risk of SSI related to delay in appendectomy. A
      future multi-institutional study is planned to confirm these results.

PMID- 24888857
TI  - Use of mechanical bowel preparation and oral antibiotics for elective colorectal
      procedures in children: is current practice evidence-based?
AB  - PURPOSE: It is well established through randomized trials that oral antibiotics
      given with or without a mechanical bowel preparation (MBP) prior to colorectal
      procedures reduce complications, while MBP given alone provides no benefit. We
      aimed to characterize trends surrounding bowel preparation in children and
      determine whether contemporary practice is evidence-based. METHODS: Retrospective
      analysis of patients undergoing colorectal procedures at 42 children's hospitals
      (1/2/2007-12/31/2011) was performed. Patients were analyzed for diagnosis, pre
      admission status, and inpatient bowel preparation. Bowel preparation was
      considered evidence-based if oral antibiotics were utilized with or without a
      MBP. RESULTS: 49% of all patients were pre-admitted (n=5,473), and the most
      common diagnoses were anorectal malformations (55%), inflammatory bowel disease
      (26%), and Hirschsprung's Disease (19%). The most common preparation approaches
      were MBP alone (54.3%), MBP+oral antibiotics (18.8%), and oral antibiotics alone
      (4.2%), although significant variation was found in hospital-specific rates for
      each approach (MBP alone: 0-96.1%, MBP+oral antibiotics: 0-83.6%, orals alone: 0
      91.6%, p<0.0001). Only 22.9% of all patients received an evidence-based
      preparation (range by hospital: 0-92.3%, p<0.0001), and this rate decreased
      significantly during the five-year study period (27.6% in 2007 vs. 17.3% in 2011,
      p<0.0001). CONCLUSION: According to the best available clinical evidence, less
      than a quarter of all children pre-admitted for elective colorectal procedures
      receive a bowel preparation proven to reduce infectious complications.

PMID- 24888858
TI  - Initial bladder closure of the cloacal exstrophy complex: outcome related risk
      factors and keys to success.
AB  - PURPOSE: This study examines a large single-institution experience with cloacal
      exstrophy patients, analyzing patient demographics and surgical strategies
      predictive of bladder closure outcomes. METHODS: One hundred patients with
      cloacal exstrophy were identified. Complete closure history including
      demographics, operative history, and outcomes was available on 60 patients.
      Twenty-six patients with a history of failed initial bladder closure were
      compared to 34 with a history of successful initial bladder closure. Univariate
      logistic regression analysis was used to compare the two groups. RESULTS: Median
      follow up time after initial closure was 9years (range: 13months-29years). A 1cm
      increase in pre-closure diastasis resulted in a 2.64 increase in the odds of
      initial closure failure (p=0.004). Protective strategies against failure included
      delaying closure (per month) (OR=0.894, p=0.009), employing pelvic osteotomies
      (OR=0.095, p<0.001), and applying external fixation (OR=0.024; p=0.001). Among
      patients who underwent osteotomy (31% of patients in the failed group, 82% in the
      successful group), a longer delay between osteotomy and closure (OR=0.033;
      p=0.005) was also protective against failure. CONCLUSION: Patients with a large
      diastasis are more likely to fail initial closure. Delaying initial closure for
      at least 3months, performing pelvic osteotomy, and using an external fixation
      device post-operatively are strategies that improve closure success.

PMID- 24888859
TI  - Summary of the 65th Annual Meeting of the American Academy of Pediatrics Section
      on Surgery, Orlando, FL, October 25-27, 2013.
AB  - This is a summary of the 65th Annual Meeting of the American Academy of
      Pediatrics Section on Surgery held in Orlando, Florida, from October 25-27, 2013.

PMID- 24888860
TI  - Single instrument intracorporeal knot tying during single port laparoscopic
      hernia repair in children: a new simplified technique.
AB  - BACKGROUND: With the increasing number of open surgical procedures shifting to
      laparoscopy, laparoscopic suturing and knot tying are becoming integral parts of
      the skills that any laparoscopist must acquire. It is the most difficult step in
      laparoscopic surgery, especially in single incision pediatric endosurgery
      (SIPES). It needs special laparoscopic skills and very long learning curve. The
      aim of this study is to introduce a new simplified technique for single
      instrument intracorporeal suture tying during single incision laparoscopic hernia
      repair (SILHR). PATIENTS AND METHODS: This study was conducted at Al-Azhar
      University Hospitals between June 2008 and June 2010. Three-hundred and eighty
      three patients with 402 congenital inguinal hernias were subjected to SILHR using
      percutaneous insertion of purse string suture by Reverdin Needle (RN) with single
      instrument intracorporeal suture knot tie. DESCRIPTION OF THE TECHNIQUE: Under
      general endotracheal tube anesthesia, a 0.8-1.2-cm. longitudinal transumilical
      skin incision was done for insertion of the umbilical port and a 3-mm Maryland
      forceps. RN was used for insertion of a purse string suture with single
      instrument intracorporeal suture tie around internal inguinal ring (IIR). The
      purse-string knot airtightness was stress-tested by raising the intraperitoneal
      CO2 pressure to 16-24mm Hg for about 30seconds. RESULTS: A total of 383 patients
      with 402 congenital inguinal hernias were subjected to SILHR. They were 304 males
      and 79 females with a mean age of 2.2+/-2.25years. A single instrument technique
      was used for intracorporeal suture knot tie and all cases were completed
      laparoscopically without conversion. The mean operative time was 12.5+/
      3.3minutes for unilateral hernia repair and 17+/-4.37 for bilateral cases. All
      patients achieved full recovery without intraoperative or postoperative
      complications. CONCLUSION: Single instrument intracorporeal suture tie is
      feasible, simple, and rapid as it resulted in marked decrease of operative time.
      It is of low cost, secure and gives great help during SIPES surgery without
      struggling. It is a good alternative option to extra corporeal knot tying.

PMID- 24888861
TI  - Ileocecal duplication cysts: is the loss of the valve always necessary?
AB  - BACKGROUND: Ileocecal (IC) duplication cysts are enteric duplications located at
      the IC junction, not clearly identified in all the published series. The reported
      treatment is IC resection and ileocolic anastomosis. It is well known that the
      loss of the IC valve has several adverse effects. This study is aimed at
      demonstrating that cyst removal together with the common ileal wall and following
      enterorrhaphy is possible, safe, and effective in preserving the IC region.
      METHODS: Medical records of 3 patients who underwent surgery for IC duplication
      between 2003 and 2013 were retrospectively reviewed evaluating follow-up results.
      RESULTS: All patients had an antenatal diagnosis of intraabdominal cystic mass.
      In two cases associated malformations were reported. The lesions presented at
      newborn age with intermittent small bowel obstruction and required removal. No
      patients underwent IC resection. The diagnosis of duplication cyst was confirmed
      by histo-pathologic examination. The postoperative course was uneventful, even in
      the long-term follow-up. CONCLUSIONS: Our conservative approach is a simple and
      safe technique, effective in avoiding the loss of the IC valve in children with
      duplication at the IC junction.

PMID- 24888862
TI  - Chlamydiaceae and Chlamydia-like organisms in the koala (Phascolarctos cinereus)-
      organ distribution and histopathological findings.
AB  - Chlamydial infections in koalas can cause life-threatening diseases leading to
      blindness and sterility. However, little is known about the systemic spread of
      chlamydiae in the inner organs of the koala, and data concerning related
      pathological organ lesions are limited. The aim of this study was to perform a
      thorough investigation of organs from 23 koalas and to correlate their
      histopathological lesions to molecular chlamydial detection. To reach this goal,
      246 formalin-fixed and paraffin embedded organ samples from 23 koalas were
      investigated by histopathology, Chlamydiaceae real-time PCR and
      immunohistochemistry, ArrayTube Microarray for Chlamydiaceae species
      identification as well as Chlamydiales real-time PCR and sequencing. By PCR, two
      koalas were positive for Chlamydia pecorum whereas immunohistochemical labelling
      for Chlamydiaceae was detected in 10 tissues out of nine koalas. The majority of
      these (n=6) had positive labelling in the urogenital tract related to
      histopathological lesions such as cystitis, endometritis, pyelonephritis and
      prostatitis. Somehow unexpected was the positive labelling in the
      gastrointestinal tract including the cloaca as well as in lung and spleen
      indicating systemic spread of infection. Uncultured Chlamydiales were detected in
      several organs of seven koalas by PCR, and four of these suffered from
      plasmacytic enteritis of unknown aetiology. Whether the finding of Chlamydia-like
      organisms in the gastrointestinal tract is linked to plasmacytic enteritis is
      unclear and remains speculative. However, as recently shown in a mouse model, the
      gastrointestinal tract might play a role being the site for persistent chlamydial
      infections and being a source for reinfection of the genital tract. 

PMID- 24888863
TI  - Strigolactone signaling regulates rice leaf senescence in response to a phosphate
      deficiency.
AB  - Strigolactones (SLs) act as plant hormones that inhibit shoot branching and
      stimulate secondary growth of the stem, primary root growth, and root hair
      elongation. In the moss Physcomitrella patens, SLs regulate branching of
      chloronemata and colony extension. In addition, SL-deficient and SL-insensitive
      mutants show delayed leaf senescence. To explore the effects of SLs on leaf
      senescence in rice (Oryza sativa L.), we treated leaf segments of rice dwarf
      mutants with a synthetic SL analogue, GR24, and evaluated their chlorophyll
      contents, ion leakage, and expression levels of senescence-associated genes.
      Exogenously applied GR24 restored normal leaf senescence in SL-deficient mutants,
      but not in SL-insensitive mutants. Most plants highly produce endogenous SLs in
      response to phosphate deficiency. Thus, we evaluated effects of GR24 under
      phosphate deficiency. Chlorophyll levels did not differ of in the wild-type
      between the sufficient and deficient phosphate conditions, but increased in the
      SL-deficient mutants under phosphate deficiency, leading in the strong promotion
      of leaf senescence by GR24 treatment. These results indicate that the mutants
      exhibited increased responsiveness to GR24 under phosphate deficiency. In
      addition, GR24 accelerated leaf senescence in the intact SL-deficient mutants
      under phosphate deficiency as well as dark-induced leaf senescence. The effects
      of GR24 were stronger in d10 compared to d17. Based on these results, we suggest
      that SLs regulate leaf senescence in response to phosphate deficiency.

PMID- 24888864
TI  - Emergency patients receiving anaesthesiologist-based pre-hospital treatment and
      subsequently released at the scene.
AB  - BACKGROUND: The Mobile Emergency Care Unit in Odense, Denmark consists of a rapid
      response car, manned with an anaesthesiologist and an emergency medical
      technician. Eleven per cent of the patients are released at the scene following
      treatment. The aim of the study was to investigate which diagnoses were assigned
      to patients released at the scene following treatment, to investigate the need
      for secondary contact with the hospital and to assess mortality in patients
      released at the scene. METHODS: All records regarding patients released at the
      scene from 1 January 2008 to 31 December 2010 were investigated. In each patient,
      diagnosis as well as any renewed contact with the Mobile Emergency Care Unit or
      the hospital within 24 h was registered. RESULTS: One thousand six hundred nine:
      patients were released at the scene. Diagnoses within the category 'examination
      and investigation' [International Classification of Diseases 10th revision (ICD
      10) chapter XXI] represented the largest group of patients (28%). Diseases not
      elsewhere classified (ICD-10 chapter XVIII) including 'syncope and collapse'
      represented the second largest group of patients (24%). One hundred thirteen (7%)
      had a renewed contact with the Mobile Emergency Care Unit within 24 h. Of the 143
      victims of traffic accidents, 19 (13%) required renewed contact with the
      emergency department and one required admission to hospital (0.7%). Of all 1609
      patients, four died within 24 h of contact (0.2%). CONCLUSION: Patients treated
      and released at the scene presented poorly defined conditions. Ninety-three per
      cent of all cases required no secondary contacts with the health care system.
      However, caution should be exercised when releasing patients at the scene
      following traffic accidents.

PMID- 24888865
TI  - Clinical Mycobacterium tuberculosis isolates from the population of Lodz, Poland
      stimulated macrophages to the lower production of IL-12 and NO when compared to
      the virulent H37Rv strain.
AB  - The course of Mycobacterium tuberculosis (Mtb) infection and the outcome of
      clinically active tuberculosis depend on the complex interactions between the
      host immune system and M. tuberculosis properties. The objective of the study was
      to examine the virulence of local Mtb isolates from the population of Lodz in
      Poland. Thirty six local Mtb strains of total 234 with known transmission in the
      local community were randomly selected for the study. The production of IL-12 and
      NO by murine macrophages stimulated with Mtb isolates was assessed and compared
      to that of virulent H37Rv strain. It was found that only 3 strains generated
      significantly higher level of NO production comparing with H37Rv strain, while 21
      clinical isolates (58% of total) stimulated murine macrophages to lower (p <
      0.05) NO production. As many as ten Mtb isolates did not induced IL-12 production
      at all, and only four clinical strains induced significantly greater amounts of
      IL-12 than H37Rv strain. No correlation between IL-12 and NO production by Mtb
      isolates was found. There were no differences between clustered and non-clustered
      strains. Low macrophages activation by local Mtb isolates may indicate their high
      virulence. 

PMID- 24888866
TI  - Whole-genome sequencing to detect recent transmission of Mycobacterium
      tuberculosis in settings with a high burden of tuberculosis.
AB  - Whole genome sequencing (WGS) of Mycobacterium tuberculosis has been used to
      trace the transmission of M. tuberculosis, the causative agent of tuberculosis
      (TB). Previously published studies using WGS were conducted in developed
      countries with a low TB burden. We sought to evaluate the relative usefulness of
      traditional VNTR and SNP typing methods, WGS and epidemiological investigations
      to study the recent transmission of M. tuberculosis in a high TB burden country.
      We conducted epidemiological investigations of 42 TB patients whose M.
      tuberculosis isolates were classified into three clusters based on variable
      number tandem repeat (VNTR) typing. We applied WGS to 32 (76.2%) of the 42
      strains and calculated the pairwise genomic distances between strains within each
      cluster. Eighteen (56.3%) of the 32 strains had genomic differences >=100 SNPs
      with every other strain, suggesting that direct transmission did not likely
      occurred. Ten strains were grouped into four WGS-based clusters with genomic
      distances <=5 SNPs within each cluster, and confirmed epidemiological links were
      identified in two of these clusters. Our results indicate that WGS provides
      reliable resolution for tracing the transmission of M. tuberculosis in high TB
      burden settings. The high resolution of WGS is particularly useful to confirm or
      exclude the possibility of direct transmission events defined by traditional
      typing methods. 

PMID- 24888868
TI  - In vitro synergy of ampicillin with gentamicin, ceftriaxone and ciprofloxacin
      against Enterococcus faecalis.

PMID- 24888867
TI  - Antigenicity of Anisakis simplex s.s. L3 in parasitized fish after heating
      conditions used in the canning processing.
AB  - BACKGROUND: Some technological and food processing treatments applied to
      parasitized fish kill the Anisakis larvae and prevent infection and sensitization
      of consumers. However, residual allergenic activity of parasite allergens has
      been shown. The aim here was to study the effect of different heat treatments
      used in the fish canning processing industry on the antigen recognition of
      Anisakis L3. Bigeye tuna (Thunnus obesus) and yellowfin tuna (Thunnus albacares)
      were experimentally infected with live L3 Anisakis. After 48 h at 5 +/- 1 
      degrees C, brine was added to the muscle, which was then canned raw (live larvae)
      or heated (90  degrees C, 30 min) (dead larvae) and treated at 113  degrees C for
      60 min or at 115  degrees C for 90 min. Anisakis antigens and Ani s 4 were
      detected with anti-crude extract and anti-Ani s 4 antisera respectively. RESULTS:
      Ani s 4 decreased in all lots, but the muscle retained part of the allergenicity
      irrespective of the canning method, as observed by immunohistochemistry. Dot blot
      analysis showed a high loss of Ani s 4 recognition after canning, but residual
      antigenicity was present. CONCLUSION: The results indicate that heat treatment
      for sterilization under the conditions studied produces a decrease in Ani s 4 and
      suggest a potential exposure risk for Anisakis-sensitized patients.

PMID- 24888869
TI  - Detection of extended-spectrum beta-lactamase- and/or carbapenemase-producing
      Enterobacteriaceae directly from positive blood culture using a commercialised
      microarray technique.

PMID- 24888872
TI  - A V2O5/conductive-polymer core/shell nanobelt array on three-dimensional graphite
      foam: a high-rate, ultrastable, and freestanding cathode for lithium-ion
      batteries.
AB  - A thin polymer shell helps V2O5 a lot. Short V2O5 nanobelts are grown directly on
      3D graphite foam as a lithium-ion battery (LIB) cathode material. A further
      coating of a poly(3,4-ethylenedioxythiophene) (PEDOT) thin shell is the key to
      the high performance. An excellent high-rate capability and ultrastable cycling
      up to 1000 cycles are demonstrated.

PMID- 24888871
TI  - Detection of qnrVC and rmtB genes from a multidrug-resistant Ralstonia pickettii
      wound infection isolate in Cambodia.

PMID- 24888870
TI  - Managing drug-drug interactions in an HIV-infected patient receiving
      antiretrovirals, anti-HCV therapy and carbamazepine: a 'tour de force' for
      clinical pharmacologists.

PMID- 24888873
TI  - Anal intraepithelial neoplasia: a single centre 19 year review.
AB  - AIM: There is debate about whether the traditional three-tiered grading of anal
      intraepithelial neoplasia (AIN) should be replaced by a more reproducible two
      tiered system. In this study, we review our experience with AIN to determine the
      most suitable classification system. METHOD: We performed a retrospective review
      of all histological reports over a 19 year period. All specimens were graded on
      haemataloxin and eosin appearance and those with dysplasia had
      immunohistochemistry for p16 and Ki67 performed. RESULTS: Cases included 25
      condyloma acuminata, 11 dysplastic cases and 24 invasive squamous cell
      carcinomas. On review, 18 were classified as condyloma acuminata without
      dysplasia. Seven had AIN I, five had AIN II and six had AIN III when using a
      three-tiered system. All cases classified as dysplastic (n = 18) showed an
      increased proliferation index as measured by Ki67. p16 positivity was seen in all
      AIN III, two AIN II and none of the AIN I cases. Recurrence was not observed in
      any of the AIN I cases. Five of eleven AIN II and AIN III cases recurred or
      persisted at a similar, higher or lower grade. Both of the AIN II cases which
      recurred or persisted were p16 positive. None of the AIN II cases that were p16
      negative recurred. Three of the p16-positive AIN III cases did not recur. None of
      the 18 AIN cases progressed to carcinoma. CONCLUSION: The findings support the
      slow progression of AIN as described in the literature. In our small series, a
      two-tiered system with further subclassification of the traditional AIN II group
      using p16 appears to be clinically useful.

PMID- 24888879
TI  - Identification of the carotenoid modifying gene PALE YELLOW PETAL 1 as an
      essential factor in xanthophyll esterification and yellow flower pigmentation in
      tomato (Solanum lycopersicum).
AB  - Xanthophylls, the pigments responsible for yellow to red coloration, are
      naturally occurring carotenoid compounds in many colored tissues of plants. These
      pigments are esterified within the chromoplast; however, little is known about
      the mechanisms underlying their accumulation in flower organs. In this study, we
      characterized two allelic tomato (Solanum lycopersicum L.) mutants, pale yellow
      petal (pyp) 1-1 and pyp1-2, that have reduced yellow color intensity in the
      petals and anthers due to loss-of-function mutations. Carotenoid analyses showed
      that the yellow flower organs of wild-type tomato contained high levels of
      xanthophylls that largely consisted of neoxanthin and violaxanthin esterified
      with myristic and/or palmitic acids. Functional disruption of PYP1 resulted in
      loss of xanthophyll esters, which was associated with a reduction in the total
      carotenoid content and disruption of normal chromoplast development. These
      findings suggest that xanthophyll esterification promotes the sequestration of
      carotenoids in the chromoplast and that accumulation of these esters is important
      for normal chromoplast development. Next-generation sequencing coupled with map
      based positional cloning identified the mutant alleles responsible for the pyp1
      phenotype. PYP1 most likely encodes a carotenoid modifying protein that plays a
      vital role in the production of xanthophyll esters in tomato anthers and petals.
      Our results provide insight into the molecular mechanism underlying the
      production of xanthophyll esters in higher plants, thereby shedding light on a
      longstanding mystery.

PMID- 24888880
TI  - alpha1-Adrenergic receptor antagonists and gynecomastia. A case series from the
      Italian spontaneous reporting system and VigiBase(TM).
AB  - PURPOSE: The aim of this study was to analyze the cases of gynecomastia
      associated with alpha1A-adrenergic receptor antagonists (alpha1-ARAs) in the
      Italian spontaneous reporting system database (Rete Nazionale di Farmacovigilanza
      or RNF) and in the World Health Organization ICSRs database (VigiBase(TM)),
      focusing on tamsulosin use. METHODS: We analyzed the spontaneous reports of
      gynecomastia related to the use of alpha1-ARAs and collected from the RNF and
      from VigiBase(TM) up to December 2012. Cases of gynecomastia have been defined as
      reports associated with gynecomastia according with Medical Dictionary for
      Regulatory Activities (MedDRA). Reporting odds ratio (ROR) and Information
      Component (IC) were calculated as measures of disproportionality in RNF and
      VigiBase(TM), respectively. RESULTS: Up to December 2012, about 186,000 reports
      were recorded in the RNF. Among these, 902 reports of adverse drug reaction (ADR)
      have been associated with the use of at least one alpha1-ARAs. Of these, in 15
      cases, gynecomastia was a listed ADR: in 10, the suspected drug was tamsulosin
      (in eight, it was the sole suspect); in two, doxazosin and alfuzosin,
      respectively; and in one, terazosin. ROR for tamsulosin was 5.3 (95% CI 1.8,
      15.7). In VigiBase(TM), 84 reports of gynecomastia indicated tamsulosin as
      suspected drug. Tamsulosin-associated gynecomastia showed the highest IC value
      within this class of drugs (IC 95% 2.43). CONCLUSION: In this study, we highlight
      a possible association between gynecomastia and tamsulosin use. To our knowledge,
      this association has not been described before and could represent a potential
      signal.

PMID- 24888881
TI  - N-acetyltransferase 2 (NAT2) genotype as a risk factor for development of drug
      induced liver injury relating to antituberculosis drug treatment in a mixed
      ethnicity patient group.
AB  - PURPOSE: This study aims to assess whether NAT2 genotype affects susceptibility
      to moderate to severe liver injury in patients undergoing drug treatment for
      tuberculosis with isoniazid-containing regimens. METHODS: Twenty-six patients of
      European or South Asian ethnicity, who had suffered liver injury during treatment
      with isoniazid-containing drug regimens and 101 ethnically matched controls were
      genotyped for the NAT2*5, NAT2*6, and NAT2*7 alleles. Genotyping for additional
      polymorphisms in the NAT gene region was also performed on 20 of the 26 cases.
      NAT2 genotype frequency between cases and controls was compared. RESULTS: NAT2
      genotypes predicting a slow acetylator phenotype were found to be associated with
      an increased risk of isoniazid-related liver injury (odds ratio (OR) = 4.25 (95%
      confidence interval (CI), 1.36-13.22); p = 0.012) with 85% of the cases being
      slow acetylators compared with 56% of the controls. There was no evidence for an
      increased risk for the slow acetylator genotype in patients with the most severe
      cases of liver injury, who underwent liver transplantation. CONCLUSIONS: The NAT2
      slow acetylator genotype appears to be a significant risk factor for moderate and
      severe drug- induced liver injury. However, the overall effect size is modest and
      generally in line with effects described previously for this genotype in milder
      drug-induced liver injury. Additional genetic risk factors may also contribute.

PMID- 24888882
TI  - Improving the appropriateness of antimicrobial use in primary care after
      implementation of a local antimicrobial guide in both levels of care.
AB  - OBJECTIVE: This study aims to assess the effectiveness of multiple interventions
      carried out during the implementation of a guide, on the improvement of the
      appropriateness of antimicrobial prescribing in primary care. DESIGN: This is a
      cross-sectional before/after study carried out in Aljarafe Health Care Area
      (Andalusia, Spain), with a population of 368,728 inhabitants assisted in 37
      health centers. SUBJECTS: Subjects include patients with antibiotic prescriptions
      during 2009 (pre-intervention phase) or 2012 (postintervention phase) selected by
      simple random sampling (confidence level, 95%; accuracy, 5%), with infections
      registered in the electronic clinical history. INTERVENTIONS: This study involve
      training sessions in primary care centers and hospital services, incorporation of
      the electronic guide to the Health Care Service Websites, and incorporation of
      the guide to the Digital Health History as a tool to support decision making.
      MAIN OUTCOME: Difference on appropriate antibiotic prescribing before and after
      interventions resulted from the study. Other variables also include age, gender,
      type of pharmacy, antibiotic prescribed, number of treatments per year, infection
      site, and main comorbidities SOURCES: In addition, this study uses computerized
      pharmacy records of reimbursed and dispensed drugs and electronic medical
      histories. RESULTS: The percentage of appropriate antibiotic prescribing
      increased from 36% in 2009 to 57% in 2012 (p < 0.001) is shown. The improvement
      was observed in all age patients of any sex and was higher among working-age
      patients and patients with comorbidities. The best results were observed in the
      group of beta-lactams and in the treatment of respiratory and skin infections.
      CONCLUSION: The realization of multifactorial interventions involving
      professionals from both levels of care could be an effective strategy to improve
      the use of antimicrobials in primary care.

PMID- 24888883
TI  - Echocardiographic evaluation of patent foramen ovale and atrial septal defect.
AB  - Patent foramen ovale (PFO) is a common variant present in up to 25% of the
      population. Atrial septal defect (ASD) is a direct communication between the 2
      atrial chambers, of which the ostium secundum variety is the most common. This
      manuscript is an in depth review of the complex atrial septation, the diagnosis
      of PFO and ASD and its clinical and therapeutic implications. 

PMID- 24888885
TI  - Cancer treatment target is missed for first time.

PMID- 24888884
TI  - Ethylene signalling affects susceptibility of tomatoes to Salmonella.
AB  - Fresh fruits and vegetables are increasingly recognized as important reservoirs
      of human pathogens, and therefore, significant attention has been directed
      recently to understanding mechanisms of the interactions between plants and
      enterics, like Salmonella. A screen of tomato cultivars for their susceptibility
      to Salmonella revealed significant differences in the ability of this human
      pathogen to multiply within fruits; expression of the Salmonella genes (cysB,
      agfB, fadH) involved in the interactions with tomatoes depended on the tomato
      genotype and maturity stage. Proliferation of Salmonella was strongly reduced in
      the tomato mutants with defects in ethylene synthesis, perception and signal
      transduction. While mutation in the ripening-related ethylene receptor Nr
      resulted only in a modest reduction in Salmonella numbers within tomatoes, strong
      inhibition of the Salmonella proliferation was observed in rin and nor tomato
      mutants. RIN and NOR are regulators of ethylene synthesis and ripening. A
      commercial tomato variety heterozygous for rin was less susceptible to Salmonella
      under the greenhouse conditions but not when tested in the field over three
      production seasons. 

PMID- 24888886
TI  - Ecological niche and potential distribution of Anopheles arabiensis in Africa in
      2050.
AB  - BACKGROUND: The future distribution of malaria in Africa is likely to be much
      more dependent on environmental conditions than the current distribution due to
      the effectiveness of indoor and therapeutic anti-malarial interventions, such as
      insecticide-treated nets (ITNs), indoor residual spraying for mosquitoes (IRS),
      artemisinin-combination therapy (ACT), and intermittent presumptive treatment
      (IPT). Future malaria epidemiology is therefore expected to be increasingly
      dominated by Anopheles arabiensis, which is the most abundant exophagic mosquito
      competent to transmit Plasmodium falciparum and exhibits a wide geographic range.
      METHODS: To map the potential distribution of An. arabiensis in Africa,
      ecological niche models were fit to 20th century collection records. Many common
      species distribution modelling techniques aim to discriminate species habitat
      from the background distribution of environments. Since these methods arguably
      result in unnecessarily large Type I and Type II errors, LOBAG-OC was used to
      identify the niche boundary using only data on An. arabiensis occurrences. The
      future distribution of An. arabiensis in Africa was forecasted by projecting the
      fit model onto maps of simulated climate change following three climate change
      scenarios. RESULTS: Ecological niche modelling revealed An. arabiensis to be a
      climate generalist in the sense that it can occur in most of Africa's
      contemporary environmental range. Under three climate change scenarios, the
      future distribution of An. arabiensis is expected to be reduced by 48%-61%. Map
      differences between baseline and projected climate suggest that habitat
      reductions will be especially extensive in Western and Central Africa; portions
      of Botswana, Namibia, and Angola in Southern Africa; and portions of Sudan, South
      Sudan, Somalia, and Kenya in East Africa. The East African Rift Valley and
      Eastern Coast of Africa are expected to remain habitable. Some modest gains in
      habitat are predicted at the margins of the current range in South Sudan, South
      Africa, and Angola. CONCLUSION: In summary, these results suggest that the future
      potential distribution of An. arabiensis in Africa is likely to be smaller than
      the contemporary distribution by approximately half as a result of climate
      change. Agreement among the three modelling scenarios suggests that this outcome
      is robust to a wide range of potential climate futures.

PMID- 24888887
TI  - Ultrasound-assisted extraction of phenolic compounds from Phyllanthus emblica L.
      and evaluation of antioxidant activities.
AB  - OBJECTIVE: The objective of this study was to optimize ultrasound-assisted
      extraction of phenolic compounds from Phyllanthus emblica. METHODS: Extracts
      obtained by UAE were evaluated for their antioxidant activities. Extraction
      experiments were carried out with three factors and three levels namely
      extraction time (varying from 15 to 60 min), ethanol concentration (varying from
      50 to 90%) and frequency (varying from 28 to 56 kHz). RESULTS: The results showed
      that the UAE optimal conditions of extracting total phenol components were as
      follows: 15 min of extraction time, 60 degrees C of extraction temperature, 70%
      of ethanol concentration, 56 kHz of ultrasonic frequency and a 1: 50 solid to
      solvent ratio. Under optimal conditions, the leaching-out rate of phenolic
      compounds was up to 55.34 mg g(-1) , and the yield of crude extract of P. emblica
      was up to 56.82%. The results reveal that the yield of phenolic compounds of UAE
      (56.82%) is higher than that of conventional solvent extraction (16.78%).
      Furthermore, the antioxidant activities of ethanol extracts obtained by UAE were
      evaluated in terms of activities of DPPH (1,1'-diphenyl-2-2'-picrylhydrazyl)
      radical scavenging activity, total antioxidant activity, metal chelating
      activity, and reducing power. P. emblica extracts obtained by UAE showed high
      antioxidant activity (26.00, 50.11 and 115.91 MUg mL(-1) of IC50 values for DPPH
      radicals, total antioxidant ability and chelating ability of ferrous ion).
      CONCLUSION: The result of this study showed that UAE was a suitable method for
      the extraction of total phenolic compounds. Moreover, the author's main finding
      in this work is the fact that phenolic compounds from P. emblica show excellent
      antioxidant activity in multi-test systems.

PMID- 24888888
TI  - [3+2] Cycloaddition of propargylic alcohols and alpha-oxo ketene dithioacetals:
      synthesis of functionalized cyclopentadienes and further application in a Diels
      Alder reaction.
AB  - Cyclopentadienes are valuable intermediates in organic synthesis and also
      ubiquitous as the Cp ligands in organometallic chemistry. As part of ongoing
      efforts to develop novel organic reactions that employ functionalized alkynes, a
      [3+2] cycloaddition of propargylic alcohols and ketene dithioacetals has been
      developed, which leads to fully substituted 2,5-dialkylthio cyclopentadienes in
      good to excellent yields. In an unusual dethiolating Diels-Alder reaction, the
      cyclopentadienes were further reacted with maleimides to afford a family of novel
      fluorescent polycyclic compounds. 

PMID- 24888890
TI  - Author response.

PMID- 24888891
TI  - Are boryl radicals from amine-boranes and phosphine-boranes the most stable
      radicals?
AB  - The relative stability of the radicals that can be produced from amine-boranes
      and phosphine-boranes is investigated at the G3-RAD level of theory. Aminyl
      ([RNH](.) :BH3 ) and phosphinyl ([RPH](.) :BH3 ) radicals are systematically more
      stable than the boryl analogues, [RNH2 ]:BH2 (.) and [RPH2 ]:BH2 (.) . Despite
      similar stability trends for [RNH](.) :BH3 and [RPH](.) :BH3 radicals with
      respect to boryl radicals, there are significant dissimilarities between amine-
      and phosphine-boranes. The homolytic bond dissociation energy of the N?H bond
      decreases upon association of the amines with BH3 , whereas that of the P?H bond
      for phosphines increases. The stabilization of the free amine is much smaller
      than that of the corresponding aminyl radical, whereas for phosphines this is the
      other way around. The homolytic bond dissociation energy of the B?H bond of
      borane decreases upon complexation with both amines and phosphines. 

PMID- 24888892
TI  - Effects of long-term differential fertilization on eukaryotic microbial
      communities in an arable soil: a multiple barcoding approach.
AB  - To understand the fine-scale effects of changes in nutrient availability on
      eukaryotic soil microorganisms communities, a multiple barcoding approach was
      used to analyse soil samples from four different treatments in a long-term
      fertilization experiment. We performed PCR amplification on soil DNA with primer
      pairs specifically targeting the 18S rRNA genes of all eukaryotes and three
      protist groups (Cercozoa, Chrysophyceae-Synurophyceae and Kinetoplastida) as well
      as the ITS gene of fungi and the 23S plastid rRNA gene of photoautotrophic
      microorganisms. Amplicons were pyrosequenced, and a total of 88,706 quality
      filtered reads were clustered into 1232 operational taxonomic units (OTU) across
      the six data sets. Comparisons of the taxonomic coverage achieved based on
      overlapping assignment of OTUs revealed that half of the eukaryotic taxa
      identified were missed by the universal eukaryotic barcoding marker. There were
      only little differences in OTU richness observed between organic- (farmyard
      manure), mineral- and nonfertilized soils. However, the community compositions
      appeared to be strongly structured by organic fertilization in all data sets
      other than that generated using the universal eukaryotic 18S rRNA gene primers,
      whereas mineral fertilization had only a minor effect. In addition, a co
      occurrence based network analysis revealed complex potential interaction patterns
      between OTUs from different trophic levels, for example between fungivorous
      flagellates and fungi. Our results demonstrate that changes in pH, moisture and
      organic nutrients availability caused shifts in the composition of eukaryotic
      microbial communities at multiple trophic levels.

PMID- 24888893
TI  - Sequential hydroformylation/diels-alder processes: one-pot synthesis of
      polysubstituted cyclohexenes, cyclohexadienes, and phthalates from alkynes.
AB  - A novel, one-pot hydroformylation/Diels-Alder sequence for the synthesis of
      multisubstituted cyclohexenes, cyclohexadienes, and phthalates has been
      developed. Various alkynes were efficiently converted into the corresponding
      products in good yields and with excellent diastereoselectivity through palladium
      catalyzed hydroformylation followed by an AAD-type reaction (AAD: Amides
      Aldehydes-Dienophiles). In view of the availability of the substrates, the atom
      efficiency of the overall process, and the convenient introduction of
      substituents in the cyclohexene ring, this method complements current methods for
      the preparation of polysubstituted cyclohexane derivatives. 

PMID- 24888894
TI  - Early onset epileptic encephalopathy caused by de novo SCN8A mutations.
AB  - OBJECTIVE: De novo SCN8A mutations have been reported in patients with epileptic
      encephalopathy. Herein we report seven patients with de novo heterozygous SCN8A
      mutations, which were found in our comprehensive genetic analysis (target capture
      or whole-exome sequencing) for early onset epileptic encephalopathies (EOEEs).
      METHODS: A total of 163 patients with EOEEs without mutations in known genes,
      including 6 with malignant migrating partial seizures in infancy (MMPSI), and 60
      with unclassified EOEEs, were analyzed by target capture (28 samples) or whole
      exome sequencing (135 samples). RESULTS: We identified de novo SCN8A mutations in
      7 patients: 6 of 60 unclassified EOEEs (10.0%), and one of 6 MMPSI cases (16.7%).
      The mutations were scattered through the entire gene: four mutations were located
      in linker regions, two in the fourth transmembrane segments, and one in the C
      terminal domain. The type of the initial seizures was variable including
      generalized tonic-clonic, atypical absence, partial, apneic attack, febrile
      convulsion, and loss of tone and consciousness. Onset of seizures was during the
      neonatal period in two patients, and between 3 and 7 months of age in five
      patients. Brain magnetic resonance imaging (MRI) showed cerebellar and cerebral
      atrophy in one and six patients, respectively. All patients with SCN8A missense
      mutations showed initially uncontrollable seizures by any drugs, but eventually
      one was seizure-free and three were controlled at the last examination. All
      patients showed developmental delay or regression in infancy, resulting in severe
      intellectual disability. SIGNIFICANCE: Our data reveal that SCN8A mutations can
      cause variable phenotypes, most of which can be diagnosed as unclassified EOEEs,
      and rarely as MMPSI. Together with previous reports, our study further indicates
      that genetic testing of SCN8A should be considered in children with unclassified
      severe epilepsy.

PMID- 24888895
TI  - Are human polyomaviruses co-factors for cancers induced by other oncoviruses?
AB  - Presently, 12 human polyomaviruses are known: BK polyomavirus (BKPyV), JCPyV,
      KIPyV, WUPyV, Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, Trichodysplasia
      spinulosa-associated polyomavirus, HPyV9, HPyV10, STLPyV and HPyV12. In addition,
      the non-human primate polyomavirus simian virus 40 (SV40) seems to circulate in
      the human population. MCPyV was first described in 2008 and is now accepted to be
      an etiological factor in about 80% of the rare but aggressive skin cancer Merkel
      cell carcinoma. SV40, BKPyV and JCPyV or part of their genomes can transform
      cells, including human cells, and induce tumours in animal models. Moreover, DNA
      and RNA sequences and proteins of these three viruses have been discovered in
      tumour tissue. Despite these observations, their role in cancer remains
      controversial. So far, an association between cancer and the other human
      polyomaviruses is lacking. Because human polyomavirus DNA has been found in a
      broad spectrum of cell types, simultaneous dwelling with other oncogenic viruses
      is possible. Co-infecting human polyomaviruses may therefore act as a co-factor
      in the development of cancer, including those induced by other oncoviruses.
      Reviewing studies that report co-infection with human polyomaviruses and other
      tumour viruses in cancer tissue fail to detect a clear link between co-infection
      and cancer. Directions for future studies to elaborate on a possible auxiliary
      role of human polyomaviruses in cancer are suggested, and the mechanisms by which
      human polyomaviruses may synergize with other viruses in oncogenic transformation
      are discussed.

PMID- 24888896
TI  - Brief Communication: Seasonality of diet composition is related to brain size in
      New World Monkeys.
AB  - New World monkeys exhibit a more pronounced variability in encephalization than
      other primate taxa. In this comparative study, we tested two current hypotheses
      on brain size evolution, the Expensive Brain hypothesis and the Cognitive Buffer
      hypothesis, in a sample of 21 platyrrhine species. A high degree of habitat
      seasonality may impose an energetic constraint on brain size evolution if it
      leads to a high variation in caloric intake over time, as predicted by the
      Expensive Brain Hypothesis. However, simultaneously it may also provide the
      opportunity to reap the fitness benefits of increased cognitive abilities, which
      enable the exploitation of high-quality food resources even during periods of
      scarcity, as predicted by the Cognitive Buffer hypothesis. By examining the
      effects of both habitat seasonality and the variation in monthly diet composition
      across species, we found support for both hypotheses, confirming previous results
      for catarrhine primates and lemurs. These findings are in accordance with an
      energetic and ecological view of brain size evolution.

PMID- 24888897
TI  - Seeing pedestrians at night: effect of driver age and visual abilities.
AB  - PURPOSE: To quantify the effects of driver age on night-time pedestrian
      conspicuity, and to determine whether individual differences in visual
      performance can predict drivers' ability to recognise pedestrians at night.
      METHODS: Participants were 32 visually normal drivers (20 younger: M = 24.4 years
      +/- 6.4 years; 12 older: M = 72.0 years +/- 5.0 years). Visual performance was
      measured in a laboratory-based testing session including visual acuity, contrast
      sensitivity, motion sensitivity and the useful field of view. Night-time
      pedestrian recognition distances were recorded while participants drove an
      instrumented vehicle along a closed road course at night; to increase the
      workload of drivers, auditory and visual distracter tasks were presented for some
      of the laps. Pedestrians walked in place, sideways to the oncoming vehicles, and
      wore either a standard high visibility reflective vest or reflective tape
      positioned on the movable joints (biological motion). RESULTS: Driver age and
      pedestrian clothing significantly (p < 0.05) affected the distance at which the
      drivers first responded to the pedestrians. Older drivers recognised pedestrians
      at approximately half the distance of the younger drivers and pedestrians were
      recognised more often and at longer distances when they wore a biological motion
      reflective clothing configuration than when they wore a reflective vest. Motion
      sensitivity was an independent predictor of pedestrian recognition distance, even
      when controlling for driver age. CONCLUSIONS: The night-time pedestrian
      recognition capacity of older drivers was significantly worse than that of
      younger drivers. The distance at which drivers first recognised pedestrians at
      night was best predicted by a test of motion sensitivity.

PMID- 24888898
TI  - Plasma proteomic analysis of patients infected with H1N1 influenza virus.
AB  - This study profiled the plasma proteins of patients infected by the 2011 H1N1
      influenza virus. Differential protein expression was identified in plasma
      obtained from noninfected control subjects (n = 15) and H1N1-infected subjects (n
      = 15). Plasma proteins were separated by a 2DE large gel system and identified by
      nano-ultra performance LC-MS. Western blot assays were performed to validate
      proteins. Eight plasma proteins were upregulated and six proteins were
      downregulated among 3316 plasma proteins in the H1N1-infected group as compared
      with the control group. Of 14 up- and downregulated proteins, nine plasma
      proteins were validated by Western blot analysis. Putative protein FAM 157A,
      leucine-rich alpha 2 glycoprotein, serum amyloid A protein, and dual oxidase 1
      showed significant differential expression. The identified plasma proteins could
      be potential candidates for biomarkers of H1N1 influenza viral infection. Further
      studies are needed to develop these proteins as diagnostic biomarkers. 

PMID- 24888899
TI  - Polyhexamethylene guanidine hydrochloride shows bactericidal advantages over
      chlorhexidine digluconate against ESKAPE bacteria.
AB  - More information regarding the bactericidal properties of polyhexamethylene
      guanidine hydrochloride (PHMG) against clinically important antibiotic-resistant
      ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
      Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species)
      pathogens needs to be provided for its uses in infection control. The
      bactericidal properties of PHMG and chlorhexidine digluconate (CHG) were compared
      based on their minimum inhibitory concentrations (MICs), minimum bactericidal
      concentrations, and time-course-killing curves against clinically important
      antibiotic-susceptible and antibiotic-resistant ESKAPE pathogens. Results showed
      that PHMG exhibited significantly higher bactericidal activities against
      methicillin-resistant Staphylococcus aureus, carbapenem-resistant Klebsiella
      pneumoniae, and ceftazidime-resistant Enterobacter spp. than CHG. A slight
      bactericidal advantage over CHG was obtained against vancomycin-resistant
      Enterococcus faecium, ciprofloxacin- and levofloxacin-resistant Acinetobacter
      spp., and multidrug-resistant Pseudomonas aeruginosa. In previous reports, PHMG
      had higher antimicrobial activity against almost all tested Gram-negative
      bacteria and several Gram-positive bacteria than CHG using MIC test. These
      studies support the further development of covalently bound PHMG in sterile
      surface materials and the incorporation of PHMG in novel disinfectant formulas. 

PMID- 24888901
TI  - A nano-stripe based sensor for temperature measurement at the submicrometer and
      nano scales.
AB  - Submicrometer dual-stripe temperature sensors made from a single piece of metal
      thin film (e.g., Pd) are developed. With the narrowest sensor being 900 nm in
      width, they show sensitivity of 1-2 MUV/K for the full range of 10-300 K. The
      results confirm the size effect in Seebeck coefficient previously observed in
      microstripe sensors of the same device configuration. 

PMID- 24888900
TI  - Spurious transcription factor binding: non-functional or genetically redundant?
AB  - Transcription factor binding sites (TFBSs) on the DNA are generally accepted as
      the key nodes of gene control. However, the multitudes of TFBSs identified in
      genome-wide studies, some of them seemingly unconstrained in evolution, have
      prompted the view that in many cases TF binding may serve no biological function.
      Yet, insights from transcriptional biochemistry, population genetics and
      functional genomics suggest that rather than segregating into 'functional' or
      'non-functional', TFBS inputs to their target genes may be generally cumulative,
      with varying degrees of potency and redundancy. As TFBS redundancy can be
      diminished by mutations and environmental stress, some of the apparently
      'spurious' sites may turn out to be important for maintaining adequate
      transcriptional regulation under these conditions. This has significant
      implications for interpreting the phenotypic effects of TFBS mutations,
      particularly in the context of genome-wide association studies for complex
      traits. 

PMID- 24888903
TI  - The role of nuclear EpICD in extrahepatic cholangiocarcinoma: association with
      beta-catenin.
AB  - After intramembranous proteolysis-mediated loss of the extracellular domain of
      the epithelial cell adhesion molecule (EpEx) and release of an intracellular
      domain (EpICD) into the cytoplasm, EpICD sequentially associates with FHL2 to
      form a nuclear complex with beta-catenin and Lef-1. This association induces gene
      transcription involved in the activation of the oncogenic potential of epithelial
      cell adhesion molecule (EpCAM). We examined the localization and expression of
      EpEx, EpICD and beta-catenin in surgical specimens of extrahepatic
      cholangiocarcinoma (ECC) from 79 patients and focused on the relationship between
      nuclear expression of EpICD and beta-catenin. We also examined the role of EpICD
      by transfecting the EpICD cDNA in cholangiocarcinoma (CC) cell lines. There was a
      significant correlation between the nuclear expression of EpICD and beta-catenin
      in ECC tissues. Frequent nuclear co-localization of EpICD and beta-catenin was
      observed in cancer cells forming the invasive front. Nuclear expression of EpICD
      also significantly correlated with histologic grade of tumor. Overexpression of
      EpICD in the CC cells significantly increased the cell growth and proliferation.
      The overexpression of EpICD in the CC cells also increased the expression levels
      of the active form of beta-catenin and EpCAM target genes, such as c-myc and
      cyclin D1. Furthermore, the overexpression of EpICD significantly enhanced the
      migration and invasiveness of CC cells. Conversely, the inhibition of EpCAM in
      EpCAM-overexpressing cells by siRNA significantly decreased cell proliferation,
      migration and invasion. These results indicate that the spatial localization of
      EpICD and its mutual interaction with beta-catenin may be important in ECC
      progression and invasion. 

PMID- 24888902
TI  - Liquiritin modulates ERK- and AKT/GSK-3beta-dependent pathways to protect against
      glutamate-induced cell damage in differentiated PC12 cells.
AB  - Glutamate has a key role in the neuronal cell damage associated with Alzheimer's
      and Parkinson's diseases. Liquiritin (LQ), a major constituent of Glycyrrhiza
      Radix, possesses various pharmacological activities. The present study
      investigated the neuroprotective effect of LQ against glutamate-induced cell
      damage in the differentiated PC12 (DPC12) rat pheochromocytoma cell line.
      Pretreatment with 25 and 50 uM LQ for 3 h resulted in a significant increase in
      cell viability and inhibited excessive lactate dehydrogenase release in glutamate
      exposed DPC12 cells. LQ also ameliorated glutamate-induced nuclear and
      mitochondrial apoptotic alterations, intracellular calcium overload and the
      abnormal expression of apoptosis-related proteins, including cytochrome c, B-cell
      lymphoma (Bcl)-2 and Bcl2-associated X protein. Treatment with LQ alone or in
      combination with glutamate was found to enhance the phosphoactivation of
      extracellular signal-regulated kinases (ERKs), AKT and its downstream element
      glycogen synthase kinase-3beta (GSK3beta), in a time-dependent manner. However,
      no effect was observed on the expression of total-ERKs, -AKT and -GSK3beta.
      Furthermore, pre-incubation with 10 uM PD98059 or LY94002, inhibitors of ERK and
      phosphatidylinositide 3-kinase, respectively, for 30 min significantly suppressed
      the LQ-induced increase in glutamate-exposed DPC12 cell viability. To the best of
      our knowledge, the present study provides the first experimental evidence that LQ
      has a neuroprotective effect against glutamate toxicity in DPC12 cells,
      predominantly through the ERK and AKT/GSK-3beta pathways. Therefore, LQ may have
      potential for the treatment of neurodegenerative diseases. 

PMID- 24888904
TI  - The visiting internet Fiance/ee (VIF): an emerging group of international
      travelers.
AB  - Here we describe an emerging category of travelers called the Visiting Internet
      Fiance/ee (VIF), characterized by their travel to pursue a romantic relationship
      with an individual they have only encountered online. The VIF is not well
      identified in travel medicine literature despite having a higher risk for several
      travel-related issues including sexually transmitted infections, monetary fraud,
      and international scams. We also propose specific counseling interventions
      designed to minimize the adverse outcomes faced by the VIF traveler.

PMID- 24888905
TI  - Preparative crystallization of a single chain antibody using an aqueous two-phase
      system.
AB  - A simultaneous crystallization and aqueous two-phase extraction of a single chain
      antibody was developed, demonstrating process integration. The process conditions
      were designed to form an aqueous two-phase system, and to favor crystallization,
      using sodium sulfate and PEG-2000. At sufficiently high concentrations of PEG, a
      second phase was generated in which the protein crystallization occurred
      simultaneously. The single chain antibody crystals were partitioned to the top,
      polyethylene glycol-rich phase. The crystal nucleation took place in the sodium
      sulfate-rich phase and at the phase boundary, whereas crystal growth was
      progressing mainly in the polyethylene glycol-rich phase. The crystals in the
      polyethylene glycol-rich phase grew to a size of >50 um. Additionally,
      polyethylene glycol acted as an anti-solvent, thus, it influenced the
      crystallization yield. A phase diagram with an undersaturation zone,
      crystallization area, and amorphous precipitation zone was established. Only
      small differences in polyethylene glycol concentration caused significant shifts
      of the crystallization yield. An increase of the polyethylene glycol content from
      2% (w/v) to 4% (w/v) increased the yield from approximately 63-87%, respectively.
      Our results show that crystallization in aqueous two-phase systems is an
      opportunity to foster process integration.

PMID- 24888906
TI  - The quantification of reticulocyte maturation and neocytolysis in normal and
      erythropoietin stimulated rats.
AB  - A technique has recently been proposed for obtaining the reticulocyte (RET) age
      distribution from the flow cytometric reticulocyte count. It allows for a
      quantitative characterization of reticulocyte dynamics. In this work this
      technique was applied to characterize the blood, bone marrow and spleen
      reticulocytes in homeostatic and erythropoietically stimulated rats in order to
      determine the reticulocyte maturation times in the bone marrow and blood; and to
      confirm the presence of ineffective erythropoiesis (neocytolysis). The latter was
      done by comparing the reticulocyte removal rate from blood with bilirubin
      formation after erythropoiesis stimulation. A single subcutaneous dose (4050
      IU/kg) of recombinant human erythropoietin (rHuEPO) was administered to rats,
      then their reticulocytes were stained with thiazole orange and the distribution
      of the fluorescent signal measured using flow cytometry. The obtained signal
      distribution of the reticulocytes was transformed to the age distribution and a
      set of basic parameters reflecting reticulocyte dynamics was determined.
      Bilirubin concentrations were measured to directly assess the presence of
      reticulocyte irreversible removal. The bilirubin formation was found to be
      considerably modulated by rHuEPO and corresponded well to the determined
      reticulocyte removal rate. The initial increase and subsequent decrease of the
      reticulocyte maturation time in blood was quantitated and directly linked with
      RET mobilization from the bone marrow. A substantial number (60%) of
      reticulocytes is sequestrated during homeostasis in rats. This number increases
      and then decreases after rHuEPO administration, as also reflected by bilirubin
      formation. Flow cytometry seems to be an excellent method for studying RET
      dynamics and the presence of young RBC neocytolysis.

PMID- 24888907
TI  - Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and
      Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG)
      2014 edition.
AB  - The 'Clinical Guidelines for Obstetrical Practice, 2011 edition' were revised and
      published as a 2014 edition (in Japanese) in April 2014 by the Japan Society of
      Obstetrics and Gynecology and the Japan Association of Obstetricians and
      Gynecologists. The aims of this publication include the determination of current
      standard care practices for pregnant women in Japan, the widespread use of
      standard care practices, the enhancement of safety in obstetrical practice, the
      reduction of burdens associated with medico-legal and medico-economical problems,
      and a better understanding between pregnant women and maternity-service
      providers. The number of Clinical Questions and Answers items increased from 87
      in the 2011 edition to 104 in the 2014 edition. The Japanese 2014 version
      included a Discussion, a List of References, and some Tables and Figures
      following the Answers to the 104 Clinical Questions; these additional sections
      covered common problems and questions encountered in obstetrical practice,
      helping Japanese readers to achieve a comprehensive understanding. Each answer
      with a recommendation level of A, B or C was prepared based principally on
      'evidence' or a consensus among Japanese obstetricians in situations where
      'evidence' was weak or lacking. Answers with a recommendation level of A or B
      represent current standard care practices in Japan. All 104 Clinical Questions
      and Answers items, with the omission of the Discussion, List of References, and
      Tables and Figures, are presented herein to promote a better understanding among
      English readers of the current standard care practices for pregnant women in
      Japan. 

PMID- 24888908
TI  - Obstetrical disseminated intravascular coagulation score.
AB  - Obstetrical disseminated intravascular coagulation (DIC) is usually a very acute,
      serious complication of pregnancy. The obstetrical DIC score helps with making a
      prompt diagnosis and starting treatment early. This DIC score, in which higher
      scores are given for clinical parameters rather than for laboratory parameters,
      has three components: (i) the underlying diseases; (ii) the clinical symptoms;
      and (iii) the laboratory findings (coagulation tests). It is justifiably
      appropriate to initiate therapy for DIC when the obstetrical DIC score reaches 8
      points or more before obtaining the results of coagulation tests. Improvement of
      blood coagulation tests and clinical symptoms are essential to the efficacy
      evaluation for treatment after a diagnosis of obstetrical DIC. Therefore, the
      efficacy evaluation criteria for obstetrical DIC are also defined to enable
      follow-up of the clinical efficacy of DIC therapy. 

PMID- 24888909
TI  - Amniotic fluid embolism: pathophysiology and new strategies for management.
AB  - The registry program of amniotic fluid embolism (AFE) in Japan started in 2003.
      More than 400 hundred clinical diagnosed amniotic fluid embolism has been
      accumulated. Those data showed that there were two etiologies of AFE: the fetal
      materials create physical obstructions in the maternal microvessels in various
      organs, such as the lung; and (ii) the liquids cause an anaphylactoid reaction
      that leads to pulmonary vasospasm and activation of platelets, white blood cells
      and/or complements. The clinical findings showed that AFE was characterized
      mainly by cardiopulmonary collapse, the other involves the presence of
      disseminated intravascular coagulation (DIC) and atonic bleeding. Zinc
      coproporphyrin-1, sialyl Tn antigen (STN), complement C3, C4 and interleukin-8
      have been used as serum markers of AFE. The levels of zinc coproporphyrin-1 and
      STN were increased in cardiopulmonary collapse type AFE, and a marked reduction
      of C3 and C4 was observed in DIC type AFE. At the primary medical institution,
      initial treatments for shock airway management, vascular management, fluid
      replacement, administration of anti-DIC therapy such as antithrombin, and
      administration of fresh frozen plasma should be provided. C1 esterase inhibitor
      activity in AFE cases was significantly lower than those of normal pregnant
      women. C1 esterase inhibitor may be a promising candidate of treatment of AFE. 

PMID- 24888910
TI  - KNDy neuron as a gatekeeper of puberty onset.
AB  - Hypothalamo-pituitary-gonadal axis has been recognized as a functional unit
      orchestrating reproductive performance in mammals. The mechanism governing
      puberty onset, however, is still one of the great mysteries of biology. The
      present article reviews previous studies over the last century, which gradually
      elucidated the brain mechanism controlling puberty onset in mammals along with
      the discovery of gonadotrophins and the gonadotrophin-releasing hormone and the
      establishment of the concept for the hypothalamo-pituitary-gonadal axis. The
      discovery of kisspeptin and subsequent progress of neuroendocrinology in the last
      decade has resulted in much greater understanding of the way the brain governs
      puberty onset in mammals. 

PMID- 24888911
TI  - Concurrent use of Foley catheter and misoprostol for induction of labor: a
      randomized clinical trial of efficacy and safety.
AB  - AIM: The aim of this study was to compare the efficacy of combined intracervical
      Foley catheter and low-dose vaginal misoprostol with low-dose vaginal misoprostol
      alone for induction of labor. MATERIAL AND METHODS: This prospective non-blinded
      randomized controlled trial was conducted over a 2-year period in 126 pregnant
      women planned for induction of labor at a tertiary care centre. Women at >= 28
      gestational weeks with a singleton fetus in cephalic presentation, intact
      membranes and a Bishop score of <= 4 were randomized for labor induction with
      either a combination of Foley catheter and misoprostol or only misoprostol. The
      primary outcome variable was the induction-to-delivery interval between the two
      groups. The secondary outcome variables included rate of vaginal deliveries,
      uterine hyperstimulation, cesarean section rate, Apgar scores at 1 and 5 min,
      neonatal intensive care unit admissions and chorioamnionitis. RESULTS: The mean
      induction-to-delivery interval and rate of vaginal deliveries were not
      significantly different between the groups (26.52 h in the combination group and
      27.64 h in the misoprostol group, P = 0.65; 65.07% and 65.07%, respectively, P =
      0.9). Uterine hyperstimulation and meconium-stained liquor were significantly
      more prevalent in the misoprostol group (P = 0.001). Neonatal outcomes did not
      differ significantly between the groups. CONCLUSION: The addition of Foley
      catheter to misoprostol did not cause any statistically significant benefit in
      reducing the induction-to-delivery time. However, it reduced the incidence of
      uterine hyperstimulation and meconium-stained liquor.

PMID- 24888912
TI  - Takotsubo cardiomyopathy after cesarean: a case report and published work review
      of pregnancy-related cases.
AB  - Takotsubo cardiomyopathy (TCM) primarily affects postmenopausal women and is an
      important differential diagnosis of acute coronary syndrome. We describe a rare
      case of post-partum TCM, and present a published work review of the cases of
      pregnancy-associated TCM. A 24-year-old Japanese woman pregnant with twins
      suffered from premature membrane rupture at 31 gestational weeks. Following
      emergency cesarean delivery, she complained of sudden dyspnea. Transthoracic
      echocardiography revealed an inverted Takotsubo pattern (ejection fraction, 46%).
      On post-delivery day 8, wall motion abnormalities subsided, and she was
      discharged on post-delivery day 16. We reviewed 18 relevant cases of peripartum
      TCM from the published work. Among them, 16 cases were post-partum and two cases
      occurred during pregnancy. Most women (81%) underwent cesarean delivery, and the
      first symptoms of TCM appeared during surgery in 38% of the cases. The dominant
      symptoms were chest pain (44%) and dyspnea (28%). Most cases (94%) exhibited
      electrocardiogram abnormalities, including ST changes and T-wave inversion. Serum
      levels of cardiac enzymes were abnormally high in 92% of the cases. Repeated
      echocardiography documented normalized left ventricular systolic function within
      6 months in all cases. This case and review emphasize that TCM may be concealed
      in post-partum women by symptoms undistinguishable from acute coronary syndrome,
      peripartum cardiomyopathy or pulmonary thromboembolism, and that echocardiography
      may be a useful tool to distinguish them. 

PMID- 24888914
TI  - Preterm birth trend in Taiwan from 2001 to 2009.
AB  - AIM: The aim of this study was to analyze the trends and risk factors of preterm
      birth from all the women who delivered during 2001-2009 in Taiwan. MATERIAL AND
      METHODS: We analyzed the preterm birth rates, the proportions of obstetric
      antecedents and risk factors in the population of pregnant women and neonatal
      Apgar scores according to the National Medical Birth Register database from 2001
      to 2009. Adjusted odds ratios (OR) with 95% confidence intervals for risk factors
      of preterm birth were assessed using multivariable logistic regression models.
      The obstetric antecedents of preterm birth for singletons were stratified by
      spontaneous preterm labor and indicated preterm delivery (labor induction or
      elective cesarean delivery). RESULTS: The preterm birth rate was 8.56% with the
      majority (89.76%) delivered between 32 and 37 weeks of gestation. A 0.07% annual
      increase (P < 0.001) in preterm delivery was observed. The greatest risk factors
      were multiple pregnancies (OR > 20), followed by medical complications (OR >
      2.8), congenital malformations (OR > 2), teen pregnancies (OR > 1), and advanced
      maternal age (OR > 1). Specifically, singleton preterm births comprised 57.3%
      spontaneous labor and 42.7% indicated delivery. There was a 0.5% annual increase
      (P < 0.001) in indicated delivery. Incidence of neonates with poor Apgar scores
      (<7) was significantly different between those with and without medical
      complications (P < 0.001). CONCLUSIONS: The preterm birth rate increased
      significantly from 2001 to 2009 and multiple pregnancies were the most important
      contributing factor. Most of the singleton preterm births resulted from
      spontaneous labor, but the proportion of indicated deliveries increased.

PMID- 24888915
TI  - Comparative study of placental alpha-microglobulin-1, insulin-like growth factor
      binding protein-1 and nitrazine test to diagnose premature rupture of membranes:
      a randomized controlled trial.
AB  - AIM: The aim of this study was to compare the accuracy of placental alpha
      microglobulin-1 (PAMG-1), insulin-like growth factor binding protein-1 (IGFBP-1)
      and nitrazine test to diagnose premature rupture of membranes. MATERIAL AND
      METHODS: A total of 120 pregnant women between 11 and 42 weeks with
      signs/symptoms of membrane rupture were eligible for our study. These women were
      evaluated with the PAMG-1, IGFBP-1, and nitrazine tests. RESULTS: In the 120
      women, the sensitivity, specificity, positive predictive value, and negative
      predictive value of PAMG-1, IGFBP-1 and nitrazine test were 100%, 100%, 100%, and
      100%, 93.33%, 98.89%, 96.55% and 97.80%, and 93.33%, 94.44%, 84.85%, and 97.7%,
      respectively. In a comparison of the PAMG-1 test and the nitrazine test, positive
      coincidence rate was 84.85%, negative coincidence rate was 97.70%, total
      coincidence rate was 94.17%, and kappa value was 0.85. In a comparison of the
      PAMG-1 test and the IGFBP-1 test, the positive coincidence rate, negative
      coincidence rate and total coincidence rate were 96.55%, 97.80%, and 97.50%, and
      kappa value was 0.93. CONCLUSION: PAMG-1 assay was the most accurate method to
      diagnose premature rupture of membranes with the highest sensitivity,
      specificity, positive predictive value and negative predictive value.

PMID- 24888913
TI  - Mid-trimester maternal serum and amniotic fluid biomarkers for the prediction of
      preterm delivery and intrauterine growth retardation.
AB  - AIM: Our purpose was to evaluate the predictive value of maternal serum and
      amniotic fluid biomarkers that were obtained at the time of genetic amniocentesis
      for preterm delivery and intrauterine growth retardation (IUGR). METHODS: A
      prospective cohort analysis was conducted in 107 singleton pregnancies that
      underwent amniocentesis at 16-22 weeks according to standard genetic indications.
      Maternal blood and amniotic fluid obtained from genetic amniocentesis were tested
      for glucose, alkaline phosphatase (ALP), lactate dehydrogenase (LDH),
      ceruloplasmin, ferritin, high-sensitivity C-reactive protein and interleukin-6
      (IL-6). Ninety-four pregnancies were followed until delivery. RESULTS: Of the 94
      patients, 16 (18.1%) delivered before 37 weeks and seven (7.5%) delivered a baby
      below the 10th percentile for gestational age. Amniotic fluid glucose levels were
      significantly lower in patients with preterm delivery than term deliveries (P =
      0.01). Median amniotic fluid ferritin and IL-6 levels and mean amniotic fluid ALP
      levels were higher in the preterm group but this difference did not reach
      statistical significance. Mean maternal ALP and LDH levels tended to be
      insignificantly higher. Only median maternal blood ferritin levels in the IUGR
      group were found to be higher than patients who were appropriate for gestational
      age (P = 0.03). CONCLUSION: Low amniotic fluid glucose levels are associated with
      risk of preterm delivery, whereas high maternal blood ferritin levels increase
      the risk for IUGR. Although this result is significant and notable, there is not
      enough clinical evidence to recommend their use as a screening test for preterm
      delivery and IUGR in routine practice.

PMID- 24888916
TI  - Frequency of hereditary thrombophilia in women with recurrent pregnancy loss in
      Northern Pakistan.
AB  - AIM: Hereditary thrombophilia (HT) screening is performed as routine work-up of
      recurrent pregnancy loss (RPL) in Pakistan. In Northern Pakistan the prevalence
      of HT is not known. HT is not detected in the majority of RPL cases, especially
      in patients with <= 3 pregnancy losses (PL). The aim of this study was to
      determine the frequency of HT in women with RPL, and to find the prevalence of HT
      in patients with <= 3 PL and > 3 PL. MATERIAL AND METHODS: Lupus-anticoagulant
      negative patients with unexplained RPL were screened for protein C, protein S,
      antithrombin, and factor V Leiden. RESULTS: A total of 315 patients with RPL were
      screened and 13 (4%) had evidence of HT. Protein C and protein S deficiency were
      detected in 6/140 (4.3%) women with > 3 PL and in 2/175 (1.1%) women with <= 3
      PL. Antithrombin deficiency was detected in 2/140 (0.75%) women with > 3 PL and
      in no patients with <= 3 PL. Factor V Leiden was detected in 3/26 (12%) women
      with > 3 PL and in no patients with <= 3 PL. The prevalence of HT in patients
      with >3 PL was significantly higher than in patients with <= 3 PL (P = 0.002). We
      detected a strong association between HT and >3 PL (odds ratio 7.3; 95%
      confidence interval: 1.60-33.85) as compared to <= 3 PL. CONCLUSION: HT was
      detected in 4% of patients with RPL. The prevalence of HT in patients with > 3 PL
      is significantly higher than in patients with <= 3 PL.

PMID- 24888917
TI  - Clinical analysis of 65 cases of hyperemesis gravidarum with gestational
      transient thyrotoxicosis.
AB  - AIM: We investigated thyroid function and the impact of gestational transient
      thyrotoxicosis (GTT) on pregnancy outcome in patients with hyperemesis gravidarum
      (HG; n = 143) who were hospitalized for rehydration. METHODS: Serum thyroid
      stimulating hormone (TSH), free T3 (FT3), free T4 (FT4), thyroid globulin
      antibody (TgAb), thyroid peroxidase antibody (TPOAb) and hCG were measured after
      admission. RESULTS: The total prevalence of thyrotoxicosis in HG was 48.3%; GTT
      was the main form (45.5%). The total incidence of GTT increased significantly if
      serum hCG was more than 80,000 IU/L, subclinical GTT if serum hCG was 80,000
      140,000 IU/L and clinical GTT if serum hCG was more than 180,000 IU/L. GTT did
      not require antithyroid therapy. The course of TSH, FT3 and FT4 were followed in
      34 cases of GTT; thyroid function normalized by the second trimester. Of 65
      patients with GTT, two underwent abortions due to unplanned pregnancies, two
      delivered prematurely and two infants had macrosomia. There were no other
      complications. All newborns (n = 63) of mothers with GTT had normal TSH levels.
      CONCLUSION: GTT is common in HG. The severity of GTT is related to serum hCG
      levels. In patients with HG and GTT, thyroid function normalized by the second
      trimester without antithyroid treatment. GTT did not affect pregnancy outcomes.

PMID- 24888918
TI  - Face presentation at term: a forgotten issue.
AB  - AIM: To determine factors associated with face presentation of term fetuses
      delivered. METHODS: Of 34,480 consecutive, term deliveries of uncomplicated
      pregnancies within a 3-year period, all live, singleton term fetuses with
      cephalic presentation in which no lethal anomalies occurred that were diagnosed
      with a face presentation were studied. Factors that may have contributed to the
      etiology of the presentation including age, parity and fetal size were evaluated.
      Ultrasonographic evaluation was recorded. RESULTS: Fifty cases were diagnosed
      with an incidence of 0.14%. Parity was not associated with face presentation.
      Birthweight of 4000 g or more indicated an increased risk of approximately 2.9
      fold, whereas fetuses weighing 3000-3499 g were found to have a relatively
      decreased risk of face presentation when compared with the general obstetrics
      group (P = 0.015 and 0.001, risk ratio = 2.948 and 0.450, respectively). With
      physical examination, only 70% were diagnosed correctly. CONCLUSION: Face
      presentation is a rare event and birthweight more than 4000 g was found to be
      associated with face presentation. Parity is not an associated factor.

PMID- 24888919
TI  - Hypoxia-induced cytosolic calcium influx is mediated primarily by the reverse
      mode of Na+/Ca2+ exchanger in smooth muscle cells of fetal small pulmonary
      arteries.
AB  - AIM: Constriction of small pulmonary arteries and high resistance of pulmonary
      circulation are important for maintaining fetal circulation before birth. In this
      study, we investigated how cytosolic free calcium concentration ([Ca(2+)]i) in
      fetal lamb small pulmonary artery smooth muscle cells (SPASMC) was affected by
      hypoxia and regulated by calcium pumps during this process. METHODS: (Ca(2+))i in
      response to acute hypoxia was determined spectrofluorometrically with fluo-3AM in
      cultured fetal SPASMC. Chemicals or solutions, including ryanodine, 2
      aminoethoxydiphenyl borate, Ca(2+)-free solution with 20 mmol
      ethyleneglycoltetraacetic (EGTA), nimodipine, Na(+)-free medium and KB-R7943,
      were administrated at the same time point when samples were exposed to acute
      hypoxia. RESULTS: (Ca(2+))i in fetal lamb SPASMC increased under acute hypoxia. 2
      Aminoethoxydiphenyl borate, an inhibitor of inositol triphosphate calcium store,
      partially attenuated the (Ca(2+))i increase after 6-min treatment. Ryanodine, an
      inhibitor of ryanodine-sensitive calcium stores, had no effect on the (Ca(2+))i
      increase. Ca(2+)-free solution with EGTA completely abolished this increase. Both
      nimodipine, that blocks the voltage-gated calcium channel, and KB-R7943, that
      inhibits the reverse mode of Na(+)/Ca(2+) exchanger, greatly diminished the
      hypoxia-induced (Ca(2+))i increase. The inhibitory effect of KB-R7943 was
      stronger than nimodipine, evidenced by the fact that (Ca(2+))i dropped near to
      the baseline level in the presence of KB-R7943 at a later time point. Low
      extracellular Na(+) concentration enhanced the hypoxia-induced increase of
      (Ca(2+))i. CONCLUSION: These results suggest that hypoxia-induced Ca(2+) increase
      in fetal SPASMC results from cytosolic Ca(2+) influx mediated primarily by the
      reverse mode of Na(+)/Ca(2+) exchanger.

PMID- 24888920
TI  - Clinical features and prenatal risk factors for hypertensive disorders in twin
      pregnancies.
AB  - AIM: The aim of this study was to identify the incidence, clinical features, and
      prenatal risk factors for hypertensive disorders, including gestational
      hypertension (GH) and pre-eclampsia (PE), in twin pregnancies. MATERIAL AND
      METHODS: We carried out a retrospective cohort study of twin pregnancies managed
      from the first trimester onward at a single center from 2002 through 2011. We
      retrospectively evaluated the incidence, severity, time-point onset of GH or PE,
      as well as maternal and neonatal outcomes. Prenatal risk factors for disease were
      also analyzed with a multivariable logistic regression model. RESULTS: Of 742
      twin pregnancies, 165 (22%) were diagnosed with GH or PE. Five women developed GH
      or PE at <32 weeks' gestation (early onset), and the remaining 160 developed them
      at >= 32 weeks (late onset). Of all 165 cases, 110 women (66.7%) developed their
      disease during the intrapartum or postpartum period. The significant risk factors
      associated with developing a hypertensive disorder in a twin pregnancy were
      primiparity (adjusted odds ratio [aOR]: 1.77; 95% confidence interval [CI]: 1.21
      2.61), pregestational high body mass index (aOR 1.35, 95%CI: 1.08-1.70), family
      history of hypertension (aOR: 1.50; 95%CI: 1.02-2.17) and previous history of GH
      or PE (aOR 8.85; 95%CI: 2.70-29.0). CONCLUSIONS: One-fifth of the twin
      pregnancies developed GH or PE. Furthermore, more than half of the patients were
      diagnosed with the disease during the intrapartum or postpartum period.
      Significant risk factors for GH or PE in twin pregnancies were primiparity,
      pregestational body mass index, family history of hypertension, and history of a
      hypertensive disorder during a previous pregnancy. The significance of monitoring
      blood pressure after delivery for a twin pregnancy is stressed.

PMID- 24888921
TI  - Use of antidiabetic agents in the treatment of gestational diabetes mellitus in
      Germany, 2008-2012.
AB  - AIM: Adequate blood glucose control during pregnancy is important because
      gestational diabetes mellitus (GDM) is known to have adverse effects on the
      mother and child. Due to an increasing prevalence of GDM in recent years, more
      information on the use of different antidiabetic agents is required, which was
      the aim of the present study. MATERIAL AND METHODS: Data from 32 diabetic
      practices in Germany were collected from January 2008 to December 2012 and
      analyzed using the Disease Analyzer Database. All women with International
      Classification of Diseases diagnosis O24 (that is, GDM) participated, except for
      patients with known type I or II diabetes mellitus, who were excluded. Analysis
      focused on the proportion of women requiring drug treatment in general.
      Thereafter, subanalysis was performed with a focus on the administration of
      different antidiabetic agents, namely insulin, metformin, and sulfonylurea.
      RESULTS: Within the given timeframe, medication-based treatment for GDM
      significantly rose to reach 30.8% of all women with GDM. Both the administration
      of insulin and metformin grew considerably within the 5-year period with
      metformin being increasingly used without supplemental insulin and at lower
      dosages. Within the insulin treatment arm, insulin analogues became increasingly
      important. The proportion of sulfonylurea remained stable (0.2%). CONCLUSIONS:
      GDM is more often treated with antidiabetic agents and, due to the fact that
      metformin is more frequently prescribed, it can be assumed that it is
      increasingly regarded as a safe and effective alternative to insulin.

PMID- 24888922
TI  - Behcet's disease and pregnancy: a retrospective analysis of course of disease and
      pregnancy outcome.
AB  - AIM: Behcet's disease (BD) is a rare, chronic, multisystemic disease of unknown
      cause. BD is characterized by mucocutaneous, ocular, vascular and central nervous
      system manifestations and is also associated with thrombogenicity. In this
      retrospective analysis we investigated the relation between gestation and BD.
      MATERIAL AND METHODS: This retrospective study consisted of 49 pregnancies in 24
      patients with BD between January 2008 and June 2013. The following clinical and
      demographic data were obtained: maternal age, obstetric history, pregnancy
      outcome, and maternal and neonatal complications during pregnancy following
      diagnosis of BD. To avoid recall bias, the following data were collected only in
      the recent pregnancy of each patient: disease activity and use of medications
      during pregnancy. RESULTS: Sixty-three pregnancies occurred in this group and 52
      of them were after the diagnosis. Mean age of the patients at diagnosis was 21.4
      years. The duration of BD during pregnancy was 7.2 years. Fourteen patients
      (58.3%) had no symptoms during recent pregnancy. No change was observed in the
      disease activity during pregnancy in eight patients. Disease activity was
      aggravated in two patients. The rate of vascular complications was higher in
      pregnancies of patients with BD. The rates of stillbirth, pre-eclampsia, preterm
      delivery and intrauterine growth restriction did not differ between the groups.
      Perinatal mortality and neonatal intensive care unit admissions as well as low
      birthweight infants were also similar between groups. CONCLUSION: Patients with
      BD had a higher rate of vascular complications during pregnancy; however, other
      obstetric complications were not increased and neonatal outcomes were not
      negatively influenced by BD.

PMID- 24888924
TI  - Risk of cerebral palsy associated with neonatal encephalopathy in macrosomic
      neonates.
AB  - AIM: To determine whether macrosomic infants with a birthweight of 4.0 kg or more
      have increased risk of cerebral palsy associated with neonatal encephalopathy
      (Enc-CP). METHODS: A retrospective review of 132 singleton infants with Enc-CP
      fulfilling all of the following criteria: born at gestational week (GW) 37 or
      more (n = 126) or weighing 2.5 kg or more at birth (n = 116) in or after January
      2009 in Japan; no identifiable causes of cerebral palsy other than antenatal or
      intrapartum hypoxia; and exhibition of neonatal encephalopathy. National
      statistics of Japan were used to determine the numbers of infants according to
      birthweight categories. RESULTS: Of the 116 infants with a birthweight of 2.5 kg
      or more, 46 (39.7%), 49 (42.2%), 17 (14.7%) and four (3.4%) infants had
      birthweights of 2.5-2.99, 3.0-3.49, 3.5-3.99 and 4.0 kg or more, respectively.
      Corresponding figures among Japanese infants born in 2009-2011 were 42.8%, 45.4%,
      10.9% and 0.90%, respectively. Infants with a birthweight of 4.0 kg or more had a
      relative risk (95% confidence interval) of Enc-CP of 3.89 (1.52-9.95) compared to
      those with a birthweight of 2.5-2.99 kg. CONCLUSION: Japanese infants with a
      birthweight of 4.0 kg or more have increased risk of Enc-CP.

PMID- 24888923
TI  - Use of an intrauterine inflated catheter balloon in massive post-partum
      hemorrhage: a series of 52 cases.
AB  - AIM: Massive post-partum hemorrhage (PPH) is an important cause of maternal death
      that occurs as a complication of delivery. We report a large case series to
      evaluate the efficacy of uterine balloon tamponade to treat PPH avoiding
      hysterectomy. MATERIAL AND METHODS: This prospective study was conducted in two
      Italian hospitals (from December 2002 to July 2012). Fifty-two patients with PPH
      not responsive to uterotonics were treated by Rusch balloon. A follow-up was
      conducted among the study population to assess the subsequent fertility. RESULTS:
      The most frequent cause of PPH was atony (59.6%), followed by placenta previa
      (21.2%), placenta accreta (9.6%), and placenta previa and accreta (9.6%). The
      balloon success rate to control hemorrhage was 75%. From the sample of 52
      patients, 13 patients needed additional procedures. In three failure cases, other
      conservative techniques were used and the overall effectiveness of them was
      80.7%. The follow-up group consisted of 31 women. Of these women, 24 women
      (77.4%) had no further pregnancies, but only one due to sterility. Four of seven
      patients with subsequent pregnancies made it to term without complications.
      CONCLUSIONS: The Rusch balloon is effective in controlling non-traumatic PPH in
      75% of cases. It is simple to use, readily available and cheap. If necessary,
      this technique does not exclude other procedures. We suggest that this balloon
      should be included routinely in the PPH protocol.

PMID- 24888925
TI  - Adverse perinatal and neonatal outcomes in patients with chronic abruption
      oligohydramnios sequence.
AB  - AIM: Chronic abruption-oligohydramnios sequence (CAOS) is a clinical condition
      with lasting vaginal bleeding and oligohydramnios because of chronic placental
      abruption, which seems to cause preterm labor and neonatal chronic lung disease
      (CLD). This prompted us to explore the correlation between perinatal/neonatal
      outcomes and CAOS. METHODS: Patients with suspected risk of abortion with
      recurrent vaginal bleeding were divided into CAOS and non-CAOS groups, and we
      compared the perinatal/neonatal outcomes between these two groups. To examine the
      impact of chorioamnionitis (CAM) on the prognosis of CAOS, we also compared
      outcomes between the CAOS group and gestational-age-matched preterm labor due to
      CAM (CAM group). RESULTS: In the CAOS and non-CAOS groups, initial vaginal
      bleeding was seen at the first trimester. However, its duration was significantly
      longer in the CAOS group. Additionally, neonatal birthweight was lower, and small
      for-gestational-age (SGA) incidence was higher in the CAOS group. CLD was
      observed in most infants from CAOS patients. In the comparison between CAOS and
      CAM groups, birthweight was lower and SGA incidence was higher in the CAOS group.
      Moreover, CLD incidence and neonatal mortality were significantly higher, despite
      the lower incidence of severe CAM in the CAOS group. Finally, multivariate
      analysis demonstrated that duration of bleeding was a significant predictive
      factor for CAOS. CONCLUSIONS: Our observations demonstrated that patients with
      CAOS were a high-risk group for poor perinatal/neonatal outcomes. Moreover,
      episodes of recurrent and prolonged uterine bleeding were predictive factors for
      CAOS. During the first trimester, prolonged bleeding is an important sign as one
      symptom of CAOS.

PMID- 24888927
TI  - Impact of first trimester fasting glycemic levels on expression of proteoglycans
      in pregnancy.
AB  - AIM: The aim of this study was to assess the influence of glucose metabolism on
      the expression of glycosaminoglycans (GAGs) and proteoglycans (PGs) in pregnant
      women. MATERIAL AND METHODS: Seventy-six women in the first trimester of
      pregnancy (10-13 weeks) attending the Gynecologic and Obstetric Clinic,
      University of Sassari, were enrolled and gave early morning urine samples. Groups
      I, II and III included women with serum glucose values of 65-89 mg/dL, 90-99
      mg/dL and 100-125 mg/dL, respectively. Urine GAGs/PGs distribution was determined
      by electrophoresis on cellulose acetate strips. Urinary N-Acetyl-beta
      glucosaminidase was estimated kinetically. RESULTS: Analysis of urinary GAGs/PGs
      electrophoretic profiles showed a significant increase in heparan sulfate (HS)
      excretion (P = 0.017) as well as a reduced chondroitin sulfate (CS) excretion (P
      = 0.048) in the group II pregnant women compared with the group I, and higher
      values of the HS/CS ratio in groups II and III compared to group I. Furthermore,
      we observed a positive correlation among fasting blood glucose levels and the
      relative content of HS, the HS/CS and urinary trypsin inhibitor/CS ratios, and
      the N-Acetyl-beta-glucosaminidase levels. CONCLUSIONS: The assessment of risk
      factors for gestational diabetes mellitus should also take into account fasting
      blood glucose values of 90-99 mg/dL, as the findings of our study indicated an
      alteration in the metabolism of GAGs during the early stages of pregnancy.

PMID- 24888926
TI  - Evaluation of oxidative stress in placenta of fetal cardiac dysfunction rat model
      and antioxidant defenses of maternal vitamin C supplementation with the impacts
      on P-glycoprotein.
AB  - AIM: The oxidative stress of placenta during fetal heart dysfunction (FHD) is
      lack of evaluation. So, we carried out an experiment to explore whether vitamin C
      (VitC) can be supplied for placental protection under FHD and its impacts on P
      glycoprotein expression. METHODS: Fetal heart dysfunction was induced by two
      intra-amniotic injections of isoproterenol, then (VitC) was supplied. Hematoxylin
      eosin (HE) staining was used to evaluate placental histology, and oxidative
      stress was measured by total antioxidant capacity, total superoxide dismutase and
      level of advanced oxidation protein products (AOPP), as well as apoptosis rate.
      Real-time polymerase chain reaction was adopted to measure the expressions of
      superoxide dismutase-1 (Sod-1), glutathione peroxidase-1 (Gpx-1) and endothelial
      nitric oxide synthase (eNOS) in placenta. Finally, western blot was performed to
      detect P-glycoprotein expression. RESULTS: All isoproterenol twice-treated
      fetuses exhibited significant (P < 0.05) contractile dysfunction by fetal
      echocardiography compared to others. The HE staining showed severe placental
      hydrops in the FHD group, and that hydrops could be reduced by VitC treatment.
      Total antioxidant capacity and total Sod-1 decreased in FHD and elevated after
      VitC supplementation. Also, level of AOPP increased in FHD and dropped after VitC
      supplementation. Analysis of apoptosis demonstrated that there was a mild
      increase in apoptosis rate of FHD. Reductions of Sod-1 and eNOS mRNA expression
      were confirmed in FHD, but these could recovered after VitC supplementation, with
      the same tendency of the P-glycoprotein. CONCLUSION: Severe oxidative injuries
      were identified in placentas of FHD with P-glycoprotein repression. VitC
      administration can reduce the oxidative stress and rebuild the protective
      mechanism of placenta.

PMID- 24888928
TI  - Abdominal scar characteristics: do they predict intra-abdominal adhesions with
      repeat cesarean deliveries?
AB  - AIM: The aim of this study was to evaluate the relation between abdominal scar
      characteristics and the severity of intra-abdominal adhesions with repeat
      cesarean deliveries. METHODS: A total of 208 women with at least one previous
      cesarean delivery at or beyond 37 weeks of gestation who were admitted for repeat
      cesarean delivery were enrolled in this study. Scars were categorized as
      depressed, flat or elevated according to their appearance, and hyperpigmented or
      the same color as the surrounding skin according to their pigmentation status.
      Intraoperative adhesions were graded according to the modified Nair's
      classification and categorized as no adhesion, filmy or dense adhesions. RESULTS:
      No significant difference was found between women with or without adhesions
      regarding age, body mass index, gestational week at delivery, number of previous
      cesarean deliveries or the duration since the last cesarean delivery. Women with
      depressed scars had more intra-abdominal adhesions than women with flat or
      elevated abdominal scars (P = 0.013). There was no significant difference in the
      incidence of hyperpigmented and non-pigmented scars between women with or without
      adhesions (39.4% vs 41.3% and 60.6% vs 58.7%, respectively) (P > 0.05). Scar
      width was significantly larger in patients with intra-abdominal adhesions than in
      patients without adhesions (3.6 +/- 1.1 vs 3.2 +/- 0.9) (P = 0.003), whereas scar
      length did not differ significantly (15.2 +/- 1.3 vs 15.1 +/- 2.1) (P > 0.005).
      CONCLUSION: There is a relation between depressed abdominal scars and intra
      abdominal adhesions, whereas pigmentation status does not differ between women
      with or without adhesions.

PMID- 24888929
TI  - Randomized clinical trial comparing postoperative outcomes of early versus late
      oral feeding after cesarean section.
AB  - AIM: Oral feeding is likely to have an impact on early return of normal bowel
      function after uncomplicated surgery including cesarean section. This study
      compared postoperative outcomes of early versus late oral feeding regimes after
      cesarean section. METHODS: In this clinical trial, 140 pregnant women who
      underwent elective cesarean section with regional anesthesia were randomized into
      two feeding groups. In the early oral and delayed oral feeding groups, liquid
      diets were commenced 2 and 8 h after surgery, respectively. Patients able to
      tolerate the liquid diet were then gradually introduced to the regular diet. Main
      clinical outcomes included duration of hospital stay, time to return of normal
      bowel function and postoperative gastrointestinal complications. RESULTS: Time to
      return of bowel movement (7.8 +/- 2.9 vs 11.7 +/- 5 h, P < 0.0001) and time to
      mobilization (10.7 +/- 7.7 vs 13.5 +/- 5.9 h, P = 0.015) occurred significantly
      earlier in the early feeding group. CONCLUSION: Early oral feeding reduces the
      time required for return of normal bowel function. This is without significant
      detrimental effects on the incidence of gastrointestinal complications.

PMID- 24888930
TI  - Validity for assisted hatching on pregnancy rate in assisted reproductive
      technology: analysis based on results of Japan Assisted Reproductive Technology
      Registry System 2010.
AB  - AIM: The aim of this study was to assess the efficacy of assisted hatching (AH)
      in assisted reproductive technology (ART) treatment. MATERIAL AND METHODS: In
      this retrospective observational study, the data of patients who were registered
      in the National ART Registry System of Japan between January and December 2010
      were analyzed. The descriptive statistics and validity of AH in fresh embryo
      transfer (ET) and frozen-thawed ET were assessed by using multiple logistic
      regression analyses. RESULTS: From a total of 105,450 single ET, 46,029 (43.7%)
      cycles underwent AH. A total of 9737 (21.3%) and 36,292 (60.9%) cycles underwent
      AH from 45,818 fresh single ET and 59,632 frozen-thawed single ET, respectively.
      In the fresh ET patients that underwent AH, the clinical pregnancy and live birth
      rate were significantly decreased in patients of all ages compared with that of
      the non-AH group. In the frozen-thawed ET patients, there was no significant
      difference in pregnancy and live birth rate between the AH group and the non-AH
      group. CONCLUSION: AH treatment was more frequently performed in frozen-thawed ET
      patients than in fresh ET patients, and in the blastocyst stage than in the early
      cleavage stage. A significantly decreased pregnancy and live birth rate was
      observed in the fresh ET patients who underwent AH. In the frozen-thawed ET
      patients who underwent AH, improvement in the clinical pregnancy and live birth
      rate was not observed. Further studies on the indication and application of AH in
      ART treatment are required.

PMID- 24888931
TI  - Measurement of endometrial and uterine vascularity by transvaginal
      ultrasonography in predicting pregnancy outcome during frozen-thawed embryo
      transfer cycles.
AB  - AIM: An appropriate endometrial condition and vascular supply are usually
      considered essential for implantation of an embryo. This study was performed to
      assess the role of endometrial and uterine vascularity status measurement in
      predicting pregnancy outcome during frozen-thawed embryo transfer cycles.
      MATERIAL AND METHODS: A total of 70 infertile women were recruited with
      controlled ovarian stimulation followed by oocyte retrieval. After in vitro
      fertilization or intracytoplasmic sperm injection, embryos were cultured to
      blastocysts and blastocysts with good quality were selected for cryopreservation.
      After endometrial preparation, vitrified blastocysts were thawed and assisted
      hatching by zona dissection was performed. On the day of embryo transfer,
      endometrial thickness (EMT), resistance index (RI) and pulsatility index (PI) of
      sub-endometrial artery (SEA) and uterine artery (UA) were obtained by
      transvaginal sonography. The women were divided into the pregnant and non
      pregnant groups, and these variables were compared between the two groups.
      RESULTS: Patients' general demographic characteristics were not statistically
      different between the pregnant and non-pregnant groups. The overall implantation
      rate, clinical pregnancy rate, and ongoing pregnancy rate were 31.1%, 41.4% and
      28.6%, respectively. Twenty-nine patients who conceived had average EMT, RI of
      SEA, PI of SEA, RI of UA, and PI of UA values of 9.15 mm, 0.91, 2.42, 0.95, and
      3.37, respectively. Forty-one patients who did not conceive had average EMT, RI
      of SEA, PI of SEA, RI of UA, and PI of UA values of 9.31 mm, 1.01, 2.56, 0.94,
      and 3.00, respectively. In the two groups, none of the variables was
      statistically different (P > 0.05). CONCLUSIONS: EMT and blood flow index of
      endometrium and uterus measured by transvaginal sonography are not an effective
      predictor of pregnancy outcome in frozen-thawed embryo transfer cycles.

PMID- 24888932
TI  - Importance of optimal local uterine blood flow for implantation.
AB  - AIMS: The aim of this study was to determine whether uterine blood flow is an
      effective parameter to anticipate uterine receptivity. MATERIAL AND METHODS: The
      local uterine blood flow was measured in the endometrium and on the outside of
      the uterus in mice during the early stage of pregnancy and an implantation
      failure mouse model using transient and local suppression of signal transducer
      and activator of transcription-3 activity during implantation. RESULTS: The local
      uterine blood flow was dramatically increased after mating and was decreased
      towards the time of implantation. The local uterine blood flow at 2.5 days post
      coitus in signal transducer and activator of transcription-3 decoy transferred
      mice was significantly higher than in control mice. However, the range of
      individual values was too wide to find a cut-off point. CONCLUSIONS: It is
      necessary to decrease local uterine blood flow after ovulation to prepare the
      opening implantation window. The optimal local uterine blood flow is regulated by
      time events during pregnancy. The range of individual values of uterine blood
      flow is wide using a laser Doppler blood flow meter. This parameter itself may
      not be an appropriate parameter to evaluate the prospect of uterine receptivity.

PMID- 24888933
TI  - Benefits of the antioxidant and anti-inflammatory activity of etoricoxib in the
      prevention of ovarian ischemia/reperfusion injury induced experimentally in rats.
AB  - AIM: This study is a biochemical investigation of the effect of etoricoxib, a
      selective cyclooxygenase (COX)-2 inhibitor, on ischemia/reperfusion (I/R) injury
      experimentally induced in rat ovaries. METHODS: Experimental animals were divided
      into four groups: (i) ovarian ischemia/reperfusion (IRG); (ii) 30 mg/kg
      etoricoxib + ovarian ischemia/reperfusion (EIRG-30); (iii) 60 mg/kg etoricoxib +
      ovarian ischemia/reperfusion (EIRG-60); and (iv) a sham operation (SG) control
      group. RESULTS: The results showed levels of malondialdehyde in the IRG, EIRG-30,
      EIRG-60 and SG group ovarian tissue of 20.2 +/- 3.4, 11.2 +/- 3.2, 5.5 +/- 1.9
      and 3.8 +/- 1.5 MUmol/g protein, respectively. Myeloperoxidase activity for these
      groups was 24.2 +/- 6.7, 13 +/- 2.4, 4 +/- 1.8 and 3.5 +/- 1.9 U/g protein, and
      total glutathione levels were 1.6 +/- 0.8, 4.5 +/- 1.9, 6.5 +/- 1.9 and 7.5 +/-
      2.4 nmol/g protein, respectively. COX-1 activity in IRG, EIRG-30, EIRG-60 and SG
      group rat ovarian tissue was 5.0 +/- 2.8, 12.2 +/- 2.4, 16.7 +/- 2.8 and 17.5 +/-
      4.7 U/mg protein, and COX-2 activity was 18.3 +/- 2.7, 3.5 +/- 1, 1.8 +/- 0.7 and
      0.7 +/- 0.3 U/mg protein, respectively. CONCLUSION: Etoricoxib prevented
      oxidative damage induced with I/R in rat ovarian tissue. This property of
      etoricoxib suggests that it can be clinically beneficial in the prevention of
      damage that may arise with reperfusion by detorsion for the protection of the
      ovaries against torsion.

PMID- 24888934
TI  - Comparison of oxidative status of mouse pre-antral follicles derived from
      vitrified whole ovarian tissue and vitrified pre-antral follicles in the presence
      of alpha lipoic acid.
AB  - AIM: The main goal of this study was to compare developmental competence and
      oxidative status of vitrified-warmed pre-antral follicles (VPF) with pre-antral
      follicles derived from vitrified-warmed ovarian tissue (VOF) in the presence of
      alpha lipoic acid (ALA). MATERIALS AND METHODS: Ovarian tissue and isolated pre
      antral follicles were exposed to equilibration solution and then vitrification
      solution. After thawing of LN2 snap-frozen samples, pre-antral follicles were
      cultured with or without ALA for 12 days that followed by hCG-induced ovulation.
      MII oocytes were in vitro fertilized and embryo cleavage assessed. Reactive
      oxygen species (ROS) and total antioxidant capacity (TAC) levels of cultured pre
      antral follicles were measured. RESULTS: The rates of survival, antral-like
      cavity formation, MII oocytes, fertilization, 2-cell embryo and blastocyst
      development were higher in VPF compared to VOF. These rates were higher in ALA
      supplemented groups in comparison to their respective groups. An increase and a
      decrease in ROS production and TAC levels were observed up to the 96 h during
      cultivation period, respectively. ROS level was lower in cultured VPF compared to
      VOF. In ALA-treated groups, ROS level decreased to reach comparable values of
      starting point and TAC levels increased after 24 h of culture and then remained
      constant. CONCLUSION: Developmental outcomes showed vitrification of pre-antral
      follicles is more appropriate method than that of whole ovarian tissue. Moreover,
      it seems that inclusion of ALA improved in vitro development of pre-antral
      follicles in both vitrified and non-vitrified samples.

PMID- 24888935
TI  - New myomectomy technique for diffuse uterine leiomyomatosis.
AB  - AIM: The aim of this study was to determine the effects of a new myomectomy
      technique for diffuse uterine leiomyomatosis. MATERIAL AND METHODS: To enucleate
      multiple myomas, we developed a novel myomectomy technique involving longitudinal
      dissection of the uterus in the midline. On each side of the anterior and
      posterior walls, the uterine wall was further divided into two pieces from the
      incision site. Myomas were separated into serosal and mucosal sides, and then
      enucleated for removal from the thinned myometrium. RESULTS: This procedure was
      applied for seven patients with diffuse leiomyomatosis. The mean number of myomas
      enucleated from each patient was 117 (range, 74-226). Mean total weight of
      enucleated myomas was 147.6 g (range, 59-360 g). Mean operative time was 284 min
      (range, 212-407 min). Mean blood loss was 1614 g (range, 428-4421 g), with three
      patients requiring blood transfusion. Anemia due to menorrhagia improved in all
      women. Three patients became pregnant, with two undergoing cesarean section after
      a normal course of pregnancy and giving birth to healthy babies. The third
      pregnancy ended in miscarriage. We noticed intraoperatively that myoma nodules
      were connected to each other in every case. CONCLUSIONS: This procedure should be
      considered as a therapeutic option in women suffering from symptoms of diffuse
      uterine leiomyomatosis who wish to avoid hysterectomy.

PMID- 24888936
TI  - Trends in laparoscopic surgery for hysterectomy in Korea between 2007 and 2009.
AB  - AIMS: The aims of this study are to estimate the hysterectomy rate for benign
      disease and determine recent trends in laparoscopic surgery for hysterectomies,
      including subtotal, total, and radical hysterectomy, in Korea. MATERIAL AND
      METHODS: Computerized discharge summaries from private and public hospitals for
      2007-2009 were obtained from the Health Insurance Review & Assessment Service.
      All records listing subtotal and total hysterectomies for benign disease and
      radical hysterectomies in women aged >= 16 years in each period were selected (n
      = 99,388). All women living in Korea aged >= 16 years were the denominator
      population. Laparoscopic surgery was identified when the code for laparoscopic
      materials was used. Statistical analysis included a trend test. RESULTS: The
      hysterectomy rates for benign disease were 1.48, 1.49, and 1.52/1000 women aged
      >= 16 years in 2007, 2008, and 2009, respectively, and the overall rate was
      1.49/1000 women. The trend increased (P for trend <0.001). The use of laparoscopy
      for subtotal and total hysterectomies accounted for 43.1% in 2007, 47.7% in 2008,
      and 52.0% in 2009, which showed a clear increasing trend (P for trend <0.001).
      The use of laparoscopy for radical hysterectomies comprised 26.7%, 28.7%, and
      38.2% of cases in 2007, 2008, and 2009, respectively, an increased trend (P for
      trend <0.001). CONCLUSION: The hysterectomy rate for benign disease increased
      between 2007 and 2009 in Korea. Application of laparoscopy during subtotal,
      total, and radical hysterectomies has increased significantly.

PMID- 24888937
TI  - Successful medical treatment of cesarean scar ectopic pregnancies with systemic
      multidose methotrexate: single-center experience.
AB  - AIM: The aim of this study was to investigate the efficacy, and the safety of
      systemic multidose methotrexate (MTX) for the treatment of cesarean scar
      pregnancy (CSP). MATERIAL AND METHODS: This retrospective cohort study was
      performed using records from the Department of Obstetrics and Gynecology, Erciyes
      University, between 2010 and 2012. The data were analyzed with respect to
      obstetric characteristic, course of treatment, clinical, and reproductive
      outcomes. RESULTS: A total of 13 patients were evaluated. The median gestational
      age at diagnosis was 5 weeks 5 days (range: 4-9 weeks). The mean beta human
      chorionic gonadotrophin level was 11,240.31 +/- 9812.68 IU/L (range: 2565-36,111
      IU/L). All patients were successfully treated with systemic multidose MTX
      therapy. The average MTX dose was 5.7 (range: 2-9). The interval between the
      first MTX injection and the normalization of beta human chorionic gonadotrophin
      was 8 +/- 2.27 weeks (range: 4-12 weeks). One patient showed mild leucopenia that
      reversed after the treatment. Three patients had successful uncomplicated
      intrauterine pregnancy after the treatment, which resulted in term infants.
      CONCLUSION: Systemic multidose MTX therapy is an effective and safe treatment
      method for CSP. However, further studies are needed to compare the safety,
      effectiveness and reproductive outcome of different treatment modalities in CSP.

PMID- 24888938
TI  - Evaluation of a single-visit approach to cervical cancer screening and treatment
      in Guyana: feasibility, effectiveness and lessons learned.
AB  - AIM: To evaluate a cervical cancer prevention project in Guyana utilizing visual
      inspection with acetic acid (VIA) and immediate cryotherapy in a single-visit
      approach; and to identify lessons learned to inform the improvement of cervical
      cancer prevention programs in Guyana and other low-resource settings. METHODS:
      Service records from January 2009 to June 2012 were analyzed for 18 cervical
      cancer prevention sites across Guyana. Records included women's HIV status, data
      on visual inspection with acetic acid screening and treatment status for women's
      initial and 1-year follow-up screenings, provider training and retention. A
      process evaluation was conducted in 2011 to identify programmatic strengths and
      interventions for integration, scale-up and sustainability. RESULTS: During the
      42-month interval, 21,597 new screenings were performed, reaching 95% of HIV(+)
      women enrolled in care and 17% of women aged 25-49 years in Guyana. The VIA(+)
      rate was 13% (n = 2806); 85% of women eligible for cryotherapy received immediate
      treatment. Half of VIA(+) women treated with cryotherapy or loop electrosurgical
      excision procedure returned for a 1-year follow-up screening (n = 1027); 95% were
      VIA(-) at the second screening. Non-physician providers were more likely to
      continue offering services than physicians. Most programmatic challenges were
      related to systemic rather than technical/clinical issues. CONCLUSION: The single
      visit approach-based program is feasible, effective, and when scaled up, likely
      to have an impact on overall incidence of cervical cancer. Services can be
      shifted to non-physicians for scale-up of high-quality cervical cancer prevention
      services nationally. To ensure sustainability and expansion, support structures
      should be prioritized.

PMID- 24888939
TI  - Argentophilic nucleolus organizer region as a proliferation marker in cervical
      intraepithelial neoplasia grade 1 of the uterine cervix.
AB  - AIM: p16INK4a and argentophilic nucleolus organizer region (AgNOR) can be used as
      markers for progression of cervical intraepithelial neoplasia grade 1 (CIN1) of
      the uterine cervix. Our objective was to study the predictive value of the AgNOR
      technique as a progression marker of CIN1 and its correlation with p16INK4A.
      MATERIAL AND METHODS: One uterine cervix biopsy from each of 75 patients with
      diagnosis of CIN1 was selected. All of these patients underwent a second biopsy,
      and these were also used for the study. RESULTS: The second biopsies showed:
      regression (20 patients), persistent CIN1 (38 patients), progression to CIN2 (10
      patients) and progression to CIN3 (seven patients). p16INK4A showed reactivity in
      67 of the 75 first CIN1 biopsies: 12 of the 20 cases that cleared the lesions and
      the 55 cases with persistent or progressive lesions were positive for p16INK4a
      (specificity: 40%; sensitivity: 100%; positive predictive value [PPV]: 82%;
      negative predictive value [NPV]: 100%). Samples with AgNOR areas less than 3.0
      MU(2) returned in all cases, but patients whose lesions persisted or progressed
      to CIN2/CIN3, showed AgNOR areas greater than 3.0 MU(2) in 50/55 cases
      (specificity: 100%; sensitivity: 91%; PPV: 100%; NPV: 80%). CONCLUSIONS: p16INK4a
      is expressed in a high percentage of returning lesions. AgNOR might be a better
      marker of proliferation of CIN1 than p16INK4a (PPV = 100%), which means that a
      value greater than 3.0 MU(2) indicates the persistence or progression of the
      lesion. As its NPV is 80%, a value of AgNOR area less than 3.0 MU(2) in CIN1
      leaves a margin of doubt about the future behavior of the lesion.

PMID- 24888940
TI  - Major causes of impractical brachytherapy in elderly patients with uterine
      cervical cancer.
AB  - AIM: Incomplete brachytherapy is a major risk factor for recurrence. However,
      high-dose-rate intracavitary brachytherapy has not been assessed adequately in
      elderly patients with invasive cervical cancer. The present study investigated
      the clinical importance of intracavitary brachytherapy and risk factors of
      incomplete intracavitary brachytherapy in elderly patients with cervical cancer.
      MATERIAL AND METHODS: Subjects were 76 patients aged 70-89 years old with
      invasive cervical cancer. All subjects were recruited between January 1997 and
      September 2010, and were planning to receive external beam radiation therapy
      followed by high-dose-rate intracavitary brachytherapy. Survival rates and the
      incidence of complications were compared between the 70s and 80s age groups. Risk
      factors for recurrence in elderly patients were evaluated using multivariate
      analysis, and risk factors for impractical intracavitary brachytherapy were also
      estimated. RESULTS: No significant differences were observed in 3-year
      progression-free survival rates or the incidence of complications in the two age
      groups. Cox multivariate analysis showed that histology (non-squamous cell
      carcinoma), incomplete intracavitary brachytherapy, and lymph node swelling were
      significant prognostic factors for recurrence. Impractical application was the
      major reason for incomplete treatment. Multiple logistic regression analysis
      revealed that a previous history without vaginal births (P = 0.016) was an
      independent risk factor for the impractical application, independent of tumor
      diameter >= 4 cm (P = 0.007). CONCLUSIONS: Incomplete intracavitary brachytherapy
      decreased the survival rates of elderly patients. Larger tumors and patients
      without a history of vaginal births were the two major causes of impractical
      intracavitary brachytherapy, which may be fatal, especially in elderly patients
      with bulky tumors.

PMID- 24888941
TI  - Clinicopathological study on para-aortic lymph node metastasis without pelvic
      lymph node metastasis in endometrial cancer.
AB  - AIM: One of the important risk factors for recurrence of endometrial cancer is
      lymph node metastasis. The regional lymph nodes are pelvic lymph nodes (PLN) and
      para-aortic lymph nodes (PAN). PAN metastasis was often detected in the cases
      with PLN metastasis. However, PAN metastasis not associated with PLN metastasis
      was identified in a few cases. We focused on nine cases with PAN metastasis and
      without PLN metastasis. MATERIAL AND METHODS: The subjects of this study were 260
      cases that were diagnosed with endometrial cancer. The initial treatments were
      surgery, including pelvic and para-aortic lymphadenectomy. Nine of these cases
      had PAN metastasis but did not have PLN metastasis. We retrospectively analyzed
      the clinicopathological factors and prognosis in cases with PLN-PAN+ cases.
      RESULTS: A total of 91 (35%) cases were identified as positive for either PLN or
      PAN. PAN metastases were detected in 62.6% of the cases that had some regional
      lymph node metastases and 3.5% of all cases were PLN- and PAN+. In all PLN-PAN+
      cases, PAN swelling was not detected by preoperative chest-abdominal computed
      tomography scan. There were no clear trends among risk factors of regional lymph
      node metastasis. The 5-year progression-free survival was 87.1% for PLN-PAN-
      cases, 67.5% for PLN+PAN- cases, 44.4% for PLN-PAN+ cases, and 33.2% for PLN+PAN+
      cases. CONCLUSION: During diagnosis and treatment for endometrial cancer, PLN
      PAN+ cases should also be considered because the prognosis in PLN-PAN+ cases
      tended to be lower than that in PLN-PAN- cases and PLN+PAN- cases.

PMID- 24888942
TI  - Therapeutic effect of laser vaporization for vaginal intraepithelial neoplasia
      following hysterectomy due to premalignant and malignant lesions.
AB  - AIM: The aim of this study was to evaluate the therapeutic effect of laser
      vaporization for vaginal intraepithelial neoplasia (VAIN) after hysterectomy in
      Chinese women and to identify factors affecting persistence/recurrence. MATERIAL
      AND METHODS: Twenty-eight VAIN patients after hysterectomy due to cervical
      intraepithelial neoplasia (group 1) and 11 VAIN patients due to cervical cancer
      (group 2) were reviewed retrospectively. All patients were treated with at least
      one episode of laser vaporization between 2010 and 2011, and then followed up
      every 3 months for at least 1 year. Cox regression analysis was used to identify
      independent factors predicting persistence/recurrence. RESULTS: All VAIN patients
      achieved remission after two episodes of laser treatment, with 85.7% complete
      regression in group 1 and 54.5% in group 2. The first episode of the treatment
      had a significantly higher success rate in group 1 than in group 2 (46.2% vs
      0.0%). All patients had no recurrence during a mean follow-up time of 22.8-27.8
      months (range 12-39 months). However, infection persisted in 21 (61.8%) of 34
      human-papillomavirus-positive patients after laser vaporization. Severity of VAIN
      was the only significant independent predictor of persistence/recurrence after
      one episode of the treatment (adjusted odds ratio, 4.08; 95% confidence interval,
      1.28-12.96; P = 0.017). Laser treatments were well tolerated with no major side
      effects. CONCLUSION: Laser vaporization may be a useful option for the treatment
      of VAIN after hysterectomy. However, a follow-up is required to assess the long
      term efficacy of laser treatment.

PMID- 24888943
TI  - Menopausal cardiomyopathy: does it really exist? A case-control deformation
      imaging study.
AB  - AIM: We aimed to evaluate and compare the left ventricular (LV) functions of pre-
      and postmenopausal women at similar ages with none of the known cardiovascular
      risk factors, by both conventional and advanced echocardiographic methods such as
      2-D strain imaging via speckle tracking echocardiography. METHODS: The study
      population consisted of 40 healthy postmenopausal women aged 45-50 years and 40
      healthy premenopausal women of the same age group. None of the subjects had any
      cardiovascular risk factors and were on hormone replacement therapy. LV strain
      and strain rate parameters were measured by 2-D strain imaging. The main outcome
      measure was effect of menopause on LV function. RESULTS: There were no
      significant differences between the pre- and postmenopausal groups with regard to
      conventional echocardiographic parameters. LV longitudinal strain and LV early
      diastolic strain rate values were significantly lower in the postmenopausal group
      when compared to the premenopausal group. Also, there was a significant negative
      correlation between LV global strain and serum follicle-stimulating hormone (r = 
      0.349, P = 0.002). CONCLUSION: Our study results demonstrated that healthy
      postmenopausal women had lower LV longitudinal strain values when compared to the
      healthy premenopausal women of the same age group by speckle tracking
      echocardiography.

PMID- 24888944
TI  - Preoperative evaluation of deep venous thrombosis in patients with pelvic organ
      prolapse.
AB  - AIM: The incidence of preoperative deep venous thrombosis (DVT) was examined in
      patients with pelvic organ prolapse (POP). MATERIAL AND METHODS: Preoperative
      screening for DVT was performed on the basis of D-dimer levels; if D-dimer levels
      were beyond the cut-off limit (0.5 MUg/mL), ultrasound examination of the lower
      extremities was performed. A total of 75 consecutive patients who were scheduled
      for POP operation in our department were examined retrospectively. RESULTS: D
      dimer levels were elevated in 24 patients (31.6%). Further, DVT was detected in
      10 of the 75 patients, resulting in an incidence rate of 13.3% in the present
      study. D-dimer levels were significantly higher in the patients with DVT (1.25 +/
      0.52 MUg/mL vs 0.41 +/- 0.26 MUg/mL). There was no significant difference in
      age, and although body mass index and the number of diabetes mellitus cases were
      relatively higher in the patients with DVT than in those without DVT, there were
      no statistically significant differences. According to a receiver-operator curve,
      the suggested cut-off D-dimer value was 0.71 MUg/mL (sensitivity and specificity
      was 0.9 and 0.877, respectively). CONCLUSIONS: Although this was a preliminary
      study, to the best of our knowledge, this is the first report describing the
      incidence of preoperative DVT in patients with POP. Our study indicates that the
      incidence of DVT in patients with POP might have been underestimated thus far.
      Therefore, every surgeon should evaluate patients for DVT prior to any surgical
      procedure for POP, particularly in those patients with obesity or diabetes
      mellitus.

PMID- 24888945
TI  - Retrospective study of tension-free vaginal mesh operation outcomes for prognosis
      improvement.
AB  - AIM: The aim of this study is to look at the weak points of tension-free vaginal
      mesh (TVM) operation for pelvic organ prolapse by reviewing recurrent cases.
      METHODS: Five hundred and twenty-six transobturator TVM operations were performed
      at the University of Occupational and Environmental Health hospital from August
      2006 to December 2011. Thirty-seven patients with pelvic organ prolapse
      quantification (POP-Q) stage II or higher after their initial operations were
      diagnosed as recurrent and were enrolled in the present study. The patients'
      characteristics, procedures of the initial and second operations, and the
      recurrence rates in the pelvic organs were retrospectively reviewed. RESULTS: The
      median age, parity and body mass index of the patients were 66.5 years (range, 48
      80), 2.2-times (range, 1-5) and 24.1 kg/m(2) (range, 17.6-32.1), respectively.
      The mean/median follow-up periods of the whole group were 29.7/35.9 months and
      the recurrent prolapse rate was 7.0% (37/526 cases). We performed reoperations in
      eight cases (8/526 cases; 1.5%). The median recurrent period after the initial
      operations was 6.9 months (range, 1-24). All recurrent cases showed severe
      prolapse with POP-Q stage III to IV before the initial operations. The uterus
      showed the most frequent recurrent prolapse after anterior posterior TVM or
      anterior TVM. CONCLUSION: Because the uterus is the most recurrent organ after
      TVM operations, TVM operations may not be sufficient for apical suspension.

PMID- 24888946
TI  - Results of tension-free vaginal tape for recurrent stress urinary incontinence
      after unsuccessful transobturator tape surgery.
AB  - AIM: The aim of this study was to evaluate cure rate and mid-term results of
      tension-free vaginal tape for recurrent stress urinary incontinence after failed
      transobturator tape surgery. MATERIAL AND METHODS: Between January 2006 and
      December 2011, 42 women were enrolled in this study. Patient characteristics and
      operating parameters were recorded, and any complications were noted. All
      patients were followed up for at least 24 months after the second surgery. The
      Incontinence Impact Questionnaire and the Urinary Distress Inventory were used to
      identify satisfaction level. RESULTS: The mean age of the patients was 49.07 +/-
      8.6 years, and median period between transobturator surgery and the tension-free
      vaginal tape procedure was 12.8 (range 9.2-17.8) months. The cure rate was 83.3%
      and 76.2% at the first- and second-year follow-up visits, respectively.
      Intraoperative complications were transient and slight. Bladder injury in five
      patients and subcutaneous hematoma above the pubis in two patients were the most
      serious complications, but they were managed conservatively. We found the scores
      of the Incontinence Impact Questionnaire and Urinary Distress Inventory to be
      significantly lower at follow-up, compared to the preoperative assessment. De
      novo urgency was the most common complaint at follow-up and occurred in 11.9% of
      the women. CONCLUSIONS: We suggest that tension-free vaginal tape is a feasible
      surgical option for recurrent stress urinary incontinence. Further studies with
      larger patient numbers and longer follow-up periods are needed to support this
      finding.

PMID- 24888947
TI  - Microbiological profile and biofilm formation on removed intrauterine
      contraceptive devices from a sample of Egyptian women.
AB  - AIM: The aim of this study was to investigate the presence of biofilm formation
      around intrauterine contraceptive devices (IUCD) and to correlate the
      microbiological profile of the IUCD-associated genital infections to the
      microbiological profile of specimens retrieved from vaginal discharge. MATERIAL
      AND METHODS: Samples of the vaginal discharge in the posterior fornix were
      collected from 50 women attending the Family Planning Clinic in Ain Shams
      University Hospital using two high vaginal swabs. Swabs were immediately sent for
      Gram staining as well as microbiological culture. The IUCD was then removed. A
      0.5-cm piece of the removed IUCD was cut and sent for culture. Growing colonies
      were tested for their abilities to form a biofilm (colorimetric method). Another
      0.5-cm piece of the removed IUCD was examined by electron microscopy (EM) for
      detection of biofilm formation. RESULTS: Among the included 50 women, 24 (48%)
      women showed biofilm formation (via colorimetric methods). EM scanning was able
      to detect biofilm formation in the prepared pieces of the removed IUCD of 48
      (96%) women. There was no significant agreement between the isolated
      microorganisms on the removed IUCD and the vaginal swab (proportion of agreement
      was 14 [11.4%]; kappa = -0.089, P = 0.892). CONCLUSION: Scanning EM is a useful
      tool in detection of biofilm formation on removed IUCD.

PMID- 24888948
TI  - Aspects of emotional and physical discomfort in gynecologic examination: a study
      of Turkish women.
AB  - AIM: This cross-sectional study was carried out to determine physical and
      emotional discomforts experienced before and after a gynecologic examination by
      women who presented to the outpatient clinic of the gynecology and obstetrics
      department at a university hospital. MATERIAL AND METHODS: The sample of study
      was composed of 248 women. Data were collected with a survey form developed by
      researchers. T-test and variance analysis were used in statistical analysis.
      RESULTS: Emotional discomfort before the examination was felt by 80.2% of the
      women, while 80.6% stated they felt emotional discomfort after the examination.
      Physical discomfort before the examination was experienced by 67.3% of the women,
      while 76.6% stated that they felt physical discomfort after the examination. The
      emotional discomfort mean score was 5.02 +/- 3.24 before examination and 4.62 +/-
      3.23 after examination (P > 0.05). The physical discomfort mean score was 3.38 +/
      3.12 before examination and 3.94 +/- 3.02 after examination and the difference
      between mean scores was statistically significant (P < 0.05). CONCLUSION: The
      women felt more physical discomfort during the examination than they anticipated
      beforehand. The emotional discomfort in women who preferred a female physician
      was significantly higher than in those who preferred a male physician or who had
      no preference on the sex of their physician.

PMID- 24888949
TI  - Domestic violence is a leading risk factor in default from colposcopy services.
AB  - AIM: Domestic violence is common in women and is associated with poorer health
      care outcomes. However, no causal pathway has been identified to explain this
      observation. We have followed a cohort of women to determine whether poorer
      outcomes can be explained by high rates of default and loss to follow-up.
      MATERIAL AND METHODS: A prospective cohort study was performed. Institutional
      ethics approval was obtained. Participants were consecutive patients attending
      colposcopy clinics at a major metropolitan hospital in Australia. Following
      ascertainment of domestic violence status, appointment outcomes for colposcopy
      services were tracked for a 3-year period. Multivariate analysis was undertaken
      to determine demographic factors associated with default from care and loss to
      follow-up. RESULTS: Of 581 women approached, consent was obtained from 574 women
      (99%). Domestic violence status was obtained from 566 women, of whom 187 (33%)
      had a recent history of exposure. Women exposed to violence were more likely to
      default from colposcopy once (26.2% vs 7.4%; P < 0.0001), twice (11.2% vs 3.2%, P
      = 0.0001), or thrice (10.7% vs 2.4%, P < 0.0001). They were more likely to be
      lost to follow-up (8.0% vs 1.1%, P < 0.0001). In multivariate analysis, exposure
      to domestic violence remained significantly associated with default and loss to
      follow-up. CONCLUSION: Domestic violence is a risk factor for default from
      attendance and loss to follow-up at colposcopy services. This may explain the
      mechanism behind adverse health-care outcomes seen. Screening and targeted
      appointment intervention programs may improve clinical compliance.

PMID- 24888950
TI  - Spontaneous rupture of uterine varicose veins: a rare cause for obstetric shock.
AB  - Spontaneous rupture of uterine surface varicose veins is rare but may result in
      serious complication of pregnancy, as it is associated with high perinatal and
      maternal mortality. We report a 24-year-old primigravida who presented with this
      rare condition mimicking placenta abruption, which was successfully managed. A
      review of reported cases was performed. 

PMID- 24888951
TI  - Two cases of recurrent abortion in which isodicentric chromosome 15 was observed
      in the husbands.
AB  - We report two cases of women positive for anticardiolipin antibodies who
      experienced recurrent abortion whose husbands had isodicentric chromosome 15
      aberrations who eventually had successful pregnancies. Two women were referred to
      our hospital due to their medical history of recurrent abortion. Both were
      diagnosed as being positive for anticardiolipin antibodies and their husbands
      with isodicentric chromosome 15. After both patients were treated with a Japanese
      herbal medicine (Sairei-to) and low-dose aspirin for the positive anticardiolipin
      antibodies, they delivered appropriate-for-date infants at term gestation.
      Although both husbands were revealed to have isodicentric chromosome 15, and
      coincidentally both wives were positive for anticardiolipin antibodies, their
      next pregnancies continued uneventfully as a result of the treatment. 

PMID- 24888952
TI  - Fetal echogenic bowel in association with Zellweger syndrome.
AB  - Increased echogenicity of fetal bowel in the second trimester obstetrical
      ultrasound has been described in association with several pathologic conditions,
      such as growth restriction, aneuploidy, cystic fibrosis, congenital infections,
      and gastrointestinal malformations. Zellweger syndrome (ZS) is the prototype of
      peroxisomal disorders characterized by craniofacial dysmorphism and severe
      neurologic abnormalities. We report two cases with fetal echogenic bowel (FEB)
      but no associated anomalies and normal fetal growth. After birth, clinical and
      laboratory findings led to diagnosis of ZS. Association of FEB with
      neurometabolic disorders is limited to a few case reports in the medical
      literature. To the best of our knowledge, this is the first report of ZS
      associated with FEB.

PMID- 24888953
TI  - Successful pregnancy in a case of bladder and ovary endometriosis following
      cystoscopy-assisted laparoscopic resection.
AB  - A 34-year-old, gravida 0 para 0 Japanese woman visited a regional hospital
      complaining of dysmenorrhea, hematuria during menstruation, and right inguinal
      pain. She had a history of dysmenorrhea and three prior rounds of in vitro
      fertilization with embryo transfer, which were all with transfers of
      cryopreserved-thawed single embryos in natural cycles, resulting in no pregnancy.
      An ultrasound revealed a large 2 * 1-cm nodule between the bladder and the
      anterior wall of the uterus and a 3-cm cystic lesion in the right adnexal area. A
      combined cystoscopic and laparoscopic resection of the bladder endometriosis and
      cystectomy of the right endometrioma were carried out. A single ultrasound-guided
      transfer of a cryopreserved-thawed embryo in the cleavage stage was performed 4
      months postoperatively, which resulted in an uncomplicated pregnancy. The
      combined, single procedure was minimally invasive and eradicated the lesions that
      may have caused the infertility.

PMID- 24888954
TI  - Disappearance of a uterine arteriovenous malformation following long-term
      administration of oral norgestrel/ethinyl estradiol.
AB  - Uterine arteriovenous malformation (AVM) can cause sudden massive hemorrhage. We
      report a case of uterine AVM following curettage in a patient treated
      conservatively with an intermediate-dose pill. An 18-year-old gravida 2 para 0
      underwent curettage at 12 weeks of gestation and was examined for massive genital
      hemorrhage that occurred in postoperative month 4. Abundant blood flow in a mass
      within the uterine lumen was observed on color Doppler ultrasonography, and the
      patient was diagnosed with AVM. Six days after starting oral norgestrel/ethinyl
      estradiol, the hemorrhage ceased, and computed tomography on day 37 of
      administration showed disappearance of the abnormal vasculature. After 12 months,
      the patient's course remains favorable without relapse. Transarterial
      embolization for AVM can cause ovarian failure and subsequent placental
      malpositioning. Administration of oral norgestrel/ethinyl estradiol may be an
      alternative conservative treatment option for patients who wish to maintain
      fertility. 

PMID- 24888955
TI  - Sonohysterography is a useful diagnostic approach for uterine arteriovenous
      malformation.
AB  - Uterine arteriovenous malformation (AVM) is a rare cause of abnormal uterine
      bleeding; nevertheless, it is a potentially life-threatening condition when the
      diagnosis is not made. We report a case of uterine AVM with a secondary uterine
      hematoma diagnosed 2 weeks after curettage due to spontaneous abortion.
      Ultrasound examination revealed a mixed echogenic mass of approximately 4 cm *
      1.5 cm with no blood flow and an additional contiguous heterogeneous mass with
      turbulent blood flow depicted by color Doppler. Transvaginal sonohysterography
      enabled us to exclude residual chorionic tissues and to make precise diagnosis of
      uterine AVM with a secondary hematoma.

PMID- 24888956
TI  - Pelvic tuberculous granuloma successfully treated with laparoscopy to preserve
      fertility: a case report and review of the published work.
AB  - Tuberculous granuloma must be considered in the differential diagnosis of pelvic
      masses in women of reproductive age because the major sequela of pelvic
      tuberculosis is infertility; however, currently there is very little information
      about its fertility-preserving treatment. We report the case of a woman with a
      history of tuberculous peritonitis who referred to our hospital for evaluation of
      an adnexal mass and primary infertility. The patient underwent excision of pelvic
      tuberculous granuloma with fertility-preserving laparoscopic surgery. We resected
      as much of the tuberculous granuloma as possible using the laparoscopic technique
      without causing damage to the uterus or ovaries. In particular, we report for the
      first time in the published work the laparoscopic removal of tuberculous
      granuloma without causing damage to the uterus or ovaries. Our experience from
      this case suggests that laparoscopic diagnosis and treatment of tuberculous
      granuloma is a feasible procedure in a patient who wants to conceive. 

PMID- 24888957
TI  - Long and fluctuating bone fragments in uterine isthmus: a curious feature of true
      osseous metaplasia.
AB  - Osseous metaplasia in the uterine cavity is a rare phenomenon arising from an
      unusual transformation of non-osseous connective tissue into mature bone. It is
      unclear how this alteration occurs and it has no single clinical manifestation.
      We report a case of asymptomatic endometrial osseous metaplasia of the isthmus
      with a singular picture: numerous long, floating bone-like structures in the
      cavity. The lesion was treated by operative hysteroscopy. Histological findings
      described a rare picture of true osseous metaplasia with the extraordinary
      presence of cells referable to areas of hematopoietic tissue in the cavities of
      trabecular bone. Physicians should be more informed and alert regarding this rare
      disorder in all its strange shapes and localizations, so as to be able to follow
      suitable therapy. 

PMID- 24888958
TI  - Primary retroperitoneal Mullerian adenocarcinoma arising from endometriosis.
AB  - Primary retroperitoneal Mullerian adenocarcinoma (PRMA) is an extremely rare
      tumor and the cause remains unknown. We report a case of PRMA arising from
      endometriosis. A 52-year-old woman with a history of malignant lymphoma underwent
      a follow-up computed tomography scan, which revealed a retroperitoneal tumor.
      Immunohistochemical analysis of tumor resected during laparoscopic surgery showed
      adenocarcinoma positive for cytokeratin 7 and negative for cytokeratin 20. The
      patient had undergone hysterectomy and bilateral salpingo-oophorectomy 14 years
      ago for myoma uteri and endometrial cysts and was treated with estrogen
      replacement therapy. The size of the tumor increased and laparotomy was
      performed. Histopathological examination showed adenocarcinoma resembling
      endometrial adenocarcinoma, which stained positive for cancer antigen 125, cancer
      antigen 19-9, estrogen receptor, and progesterone receptor immunohistochemically.
      The focus of the endometriosis was found at the edge of the tumor, and the
      stromal cells around the tumor cells were CD10 positive. The patient was
      diagnosed as having PRMA arising from endometriosis, and treated with adjuvant
      chemotherapy. 

PMID- 24888959
TI  - Case report: Renal cell carcinoma with metastasis to the myometrium.
AB  - Renal cell carcinoma (RCC) is well known for its ability to metastasize to
      different organs, but the involvement of gynecological organs is rare. Our case
      represents the first case of bilateral RCC with metastasis to the myometrium. The
      patient was a 60-year-old woman who underwent bilateral robotic partial
      nephrectomy surgeries for clear cell RCC, low-grade, low-stage with negative
      margins. Her 1-year postoperative computed tomography scan showed an enlarging
      necrotic uterine mass. She underwent a debulking excision, including
      hysterectomy, with pathology showing metastatic RCC to the uterus. The patient
      developed widespread metastatic disease, and died months later of metastatic RCC.

PMID- 24888960
TI  - Does hypoxia only influence insulin-like growth factor-1 through insulin-like
      growth factor binding protein-1?

PMID- 24888961
TI  - Authors' reply: Prognostic significance of mean platelet volume in epithelial
      ovarian cancer.

PMID- 24888962
TI  - Is the timing of scent emission correlated with insect visitor activity and
      pollination in long-spurred Satyrium species?
AB  - Plants are expected to emit floral scent when their pollinators are most active.
      In the case of long-tubed flowers specialised for pollination by crepuscular or
      nocturnal moths, scent emissions would be expected to peak during dawn. Although
      this classic idea has existed for decades, it has rarely been tested
      quantitatively. We investigated the timing of flower visitation, pollination and
      floral scent emissions in six long-spurred Satyrium species (Orchidaceae). We
      observed multiple evening visits by pollinaria-bearing moths on flowers of all
      study species, but rarely any diurnal visits. The assemblages of moth pollinators
      differed among Satyrium species, even those that co-flowered, and the lengths of
      moth tongues and floral nectar spurs were strongly correlated, suggesting that
      the available moth pollinator fauna is partitioned by floral traits. Pollinarium
      removal occurred more frequently during the night than during the day in four of
      the six species. Scent emission, however, was only significantly higher at dusk
      than midday in two species. Analysis of floral volatiles using gas chromatography
      coupled with mass spectrometry yielded 168 scent compounds, of which 112 were
      species-specific. The scent blends emitted by each species occupy discrete
      clusters in two-dimensional phenotype space, based on multivariate analysis. We
      conclude that these long-spurred Satyrium species are ecologically specialised
      for moth pollination, yet the timing of their scent emission is not closely
      correlated with moth pollination activity. Scent composition was also more
      variable than expected from a group of closely related plants sharing the same
      pollinator functional group. These findings reveal a need for greater
      understanding of mechanisms of scent production and their constraints, as well as
      the underlying reasons for divergent scent chemistry among closely related
      plants. 

PMID- 24888963
TI  - Megalencephaly and hemimegalencephaly: breakthroughs in molecular etiology.
AB  - Megalencephaly (MEG) is a developmental disorder characterized by brain
      overgrowth that occurs due to either increased number or size of neurons and
      glial cells. The former may be due to either increased neuronal proliferation or
      decreased apoptosis. The degree of brain overgrowth may be extensive, ranging
      from generalized MEG affecting the entire cortex-as with mutations in PTEN
      (phosphatase and tensin homolog on chromosome ten)-to unilateral hemispheric
      malformations-as in classic hemimegalencephaly (HME). On the other hand, some
      lesions are more focal or segmental. These developmental brain abnormalities may
      occur in isolation in some individuals, whereas others occur in the context of a
      syndrome involving dysmorphic features, skin findings, or other organ system
      involvement. Brain overgrowth disorders are often associated with malformations
      of cortical development, resulting in increased risk of epilepsy, intellectual
      disability, and autistic features, and some are associated with hydrocephalus.
      The past few years have witnessed a dramatic leap in our understanding of the
      molecular basis of brain overgrowth, particularly the identification of mosaic
      (or post-zygotic) mutations in core components of key cellular pathways such as
      the phosphatidylinositol 3-kinase (PI3K)-vakt murine thymoma viral oncogene
      homolog (AKT)-mTOR pathway. These molecular insights have broadened our view of
      brain overgrowth disorders that now appear to span a wide spectrum of overlapping
      phenotypic, neuroimaging, and neuropathologic features and molecular
      pathogenesis. These molecular advances also bring to light the possibility of
      pathway-based therapies for these often medically devastating developmental
      disorders.

PMID- 24888964
TI  - EAACI Food Allergy and Anaphylaxis Guidelines. Protecting consumers with food
      allergies: understanding food consumption, meeting regulations and identifying
      unmet needs.
AB  - Individuals suffering from IgE-mediated food allergy usually have to practise
      life-long food allergen avoidance. This document aims to provide an overview of
      recent evidence-based recommendations for allergen risk assessment and management
      in the food industry and discusses unmet needs and expectations of the food
      allergic consumer in that context. There is a general duty of care on the food
      industry and obligations in European Union legislation to reduce and manage the
      presence of allergens alongside other food hazards. Current evidence enables
      quantification of allergen reference doses used to set-up reliable food safety
      management plans for some foods. However, further work is required to include a
      wider variety of foods and to understand the impact of the food matrix as well as
      additional factors which affect the progression and severity of symptoms as a
      function of dose. Major concerns have been raised by patients, carers and patient
      groups about the use of precautionary 'may contain' labelling to address the
      issue of unintended presence of allergens; these therefore need to be
      reconsidered. New and improved allergen detection methods should be evaluated for
      their application in food production. There is an urgent requirement for
      effective communication between healthcare professionals, patient organizations,
      food industry representatives and regulators to develop a better approach to
      protecting consumers with food allergies. 

PMID- 24888965
TI  - Changes in sexual roles and quality of life for gay men after prostate cancer:
      challenges for sexual health providers.
AB  - INTRODUCTION: Gay men with prostate cancer (GMPCa) may have differential health
      related quality of life (HRQOL) and sexual health outcomes than heterosexual men
      with prostate cancer (PCa), but existing information is based on clinical
      experience and small studies. AIMS: Our goals were to: (i) describe HRQOL and
      examine changes in sexual functioning and bother; (ii) explore the psychosocial
      aspects of sexual health after PCa; and (iii) examine whether there were
      significant differences on HRQOL and sexual behavior between GMPCa and published
      norms. METHODS: A convenience sample of GMPCa completed validated disease
      specific and general measures of HRQOL, ejaculatory function and bother, fear of
      cancer recurrence, and satisfaction with prostate cancer care. Measures of self
      efficacy for PCa management, illness intrusiveness, and disclosure of sexual
      orientation were also completed. Where possible, scores were compared against
      published norms. MAIN OUTCOME MEASURES: Main outcome measures were self-reported
      sexual functioning and bother on the Expanded Prostate Cancer Index. RESULTS:
      Compared with norms, GMPCa reported significantly worse functioning and more
      severe bother scores on urinary, bowel, hormonal symptom scales (Ps < 0.015
      0.0001), worse mental health functioning (P < 0.0001), greater fear of cancer
      recurrence (P < 0.0001), and were more dissatisfied with their PCa medical care.
      However, GMPCa reported better sexual functioning scores (P < 0.002) compared
      with norms. Many of the observed differences met criteria for clinical
      significance. Physical functioning HRQOL and sexual bother scores were similar to
      that of published samples. GMPCa tended to be more "out" about their sexual
      orientation than other samples of gay men. CONCLUSIONS: GMPCa reported
      substantial changes in sexual functioning after PCa treatment. They also reported
      significantly worse disease-specific and general HRQOL, fear of recurrence, and
      were less satisfied with their medical care than other published PCa samples.
      Sexual health providers must have an awareness of the unique functional and HRQOL
      differences between gay and heterosexual men with PCa.

PMID- 24888966
TI  - Crystal structure of the C-terminal domain of mouse TLR9.
AB  - Toll-like receptors (TLRs) are important pattern recognition receptors that
      function in innate immunity. Elucidating the structure and signaling mechanisms
      of TLR9, a sensor of foreign and endogenous DNA, is essential for understanding
      its key role in immunity against microbial pathogens as well as in autoimmunity.
      Abundant evidence suggests that the TLR9-CTD (C-terminal domain) by itself is
      capable of DNA binding and signaling. The crystal structure of unliganded mouse
      TLR9-CTD is presented. TLR9-CTD exhibits one unique feature, a cluster of stacked
      aromatic and arginine side chains on its concave face. Overall, its structure is
      most related to the TLR8-CTD, suggesting a similar mode of ligand binding and
      signaling.

PMID- 24888967
TI  - Theory of mind and emotion recognition skills in children with specific language
      impairment, autism spectrum disorder and typical development: group differences
      and connection to knowledge of grammatical morphology, word-finding abilities and
      verbal working memory.
AB  - BACKGROUND: Social perception skills, such as understanding the mind and emotions
      of others, affect children's communication abilities in real-life situations. In
      addition to autism spectrum disorder (ASD), there is increasing knowledge that
      children with specific language impairment (SLI) also demonstrate difficulties in
      their social perception abilities. AIMS: To compare the performance of children
      with SLI, ASD and typical development (TD) in social perception tasks measuring
      Theory of Mind (ToM) and emotion recognition. In addition, to evaluate the
      association between social perception tasks and language tests measuring word
      finding abilities, knowledge of grammatical morphology and verbal working memory.
      METHOD & PROCEDURES: Children with SLI (n = 18), ASD (n = 14) and TD (n = 25)
      completed two NEPSY-II subtests measuring social perception abilities: (1) Affect
      Recognition and (2) ToM (includes Verbal and non-verbal Contextual tasks). In
      addition, children's word-finding abilities were measured with the TWF-2,
      grammatical morphology by using the Grammatical Closure subtest of ITPA, and
      verbal working memory by using subtests of Sentence Repetition or Word List
      Interference (chosen according the child's age) of the NEPSY-II. OUTCOMES &
      RESULTS: Children with ASD scored significantly lower than children with SLI or
      TD on the NEPSY-II Affect Recognition subtest. Both SLI and ASD groups scored
      significantly lower than TD children on Verbal tasks of the ToM subtest of NEPSY
      II. However, there were no significant group differences on non-verbal Contextual
      tasks of the ToM subtest of the NEPSY-II. Verbal tasks of the ToM subtest were
      correlated with the Grammatical Closure subtest and TWF-2 in children with SLI.
      In children with ASD correlation between TWF-2 and ToM: Verbal tasks was
      moderate, almost achieving statistical significance, but no other correlations
      were found. CONCLUSIONS & IMPLICATIONS: Both SLI and ASD groups showed
      difficulties in tasks measuring verbal ToM but differences were not found in
      tasks measuring non-verbal Contextual ToM. The association between Verbal ToM
      tasks and language tests was stronger in children with SLI than in children with
      ASD. There is a need for further studies in order to understand interaction
      between different areas of language and cognitive development.

PMID- 24888968
TI  - Deactivation of cationic Cu(I) and Au(I) catalysts for A(3) coupling by
      CH(2)C(l2) : mechanistic implications of the formation of neutral Cu(I) and Au(I)
      chlorides.
AB  - Care should be exercised when using CH2 Cl2 as a solvent for reactions in which
      amines are a reagent, since undesirable deactivation of cationic copper(I) and
      gold(I) catalysts to form the corresponding inactive neutral chloride complexes
      [LMCl] (M=Cu or Au) can occur as a result of the generation of hydrogen chloride
      in the medium. Cu(I) and Au(I) deactivation has been proved for the Mannich three
      component coupling reaction. A series of Cu(I) and Au(I) complexes with potential
      mechanistic implications were isolated and characterized by X-ray
      crystallography. 

PMID- 24888970
TI  - Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway
      uncovers functions for conserved proteins in hopanoid-producing bacteria.
AB  - Hopanoids are bacterial surrogates of eukaryotic membrane sterols and among
      earth's most abundant natural products. Their molecular fossils remain in
      sediments spanning more than a billion years. However, hopanoid metabolism and
      function are not fully understood. Burkholderia species are environmental
      opportunistic pathogens that produce hopanoids and also occupy diverse ecological
      niches. We investigated hopanoids biosynthesis in Burkholderia cenocepacia by
      deletion mutagenesis and structural characterization of the hopanoids produced by
      the mutants. The enzymes encoded by hpnH and hpnG were essential for production
      of all C35 extended hopanoids, including bacteriohopanetetrol (BHT), BHT
      glucosamine and BHT cyclitol ether. Deletion of hpnI resulted in BHT production,
      while DeltahpnJ produced only BHT glucosamine. Thus, HpnI is required for BHT
      glucosamine production while HpnJ is responsible for its conversion to the
      cyclitol ether. The DeltahpnH and DeltahpnG mutants could not grow under any
      stress condition tested, whereas DeltahpnI, DeltahpnJ and DeltahpnK displayed
      wild-type growth rates when exposed to detergent, but varying levels of
      sensitivity to low pH and polymyxin B. This study not only elucidates the
      biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a
      biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other
      hopanoid-producing bacteria.

PMID- 24888969
TI  - Controlled ocular drug delivery with nanomicelles.
AB  - Many vision threatening ocular diseases such as age-related macular degeneration
      (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may
      result in blindness. Ocular drug delivery specifically to the intraocular tissues
      remains a challenging task due to the presence of various physiological barriers.
      Nonetheless, recent advancements in the field of nanomicelle-based novel drug
      delivery system could fulfil these unmet needs. Nanomicelles consists of
      amphiphilic molecules that self-assemble in aqueous media to form organized
      supramolecular structures. Micelles can be prepared in various sizes (10-1000 nm)
      and shapes depending on the molecular weights of the core and corona forming
      blocks. Nanomicelles have been an attractive carrier for their potential to
      solubilize hydrophobic molecules in aqueous solution. In addition, small size in
      nanometer range and highly modifiable surface properties have been reported to be
      advantageous in ocular drug delivery. In this review, various factors influencing
      rationale design of nanomicelles formulation and disposition are discussed along
      with case studies. Despite the progress in the field, influence of various
      properties of nanomicelles such as size, shape, surface charge, rigidity of
      structure on ocular disposition need to be studied in further details to develop
      an efficient nanocarrier system.

PMID- 24888971
TI  - Pilot study of sorafenib in relapsed or refractory peripheral and cutaneous T
      cell lymphoma.

PMID- 24888972
TI  - The benefits and harms of providing parents with weight feedback as part of the
      national child measurement programme: a prospective cohort study.
AB  - BACKGROUND: Small-scale evaluations suggest that the provision of feedback to
      parents about their child's weight status may improve recognition of overweight,
      but the effects on lifestyle behaviour are unclear and there are concerns that
      informing parents that their child is overweight may have harmful effects. The
      aims of this study were to describe the benefits and harms of providing weight
      feedback to parents as part of a national school-based weight-screening programme
      in England. METHODS: We conducted a pre-post survey of 1,844 parents of children
      aged 4-5 and 10-11 years who received weight feedback as part of the 2010-2011
      National Child Measurement Programme. Questionnaires assessed general knowledge
      about the health risks associated with child overweight, parental recognition of
      overweight and the associated health risks in their child, child lifestyle
      behaviour, child self-esteem and weight-related teasing, parental experience of
      the feedback, and parental help-seeking behaviour. Differences in the pre-post
      proportions of parents reporting each outcome were assessed using a McNemar's
      test. RESULTS: General knowledge about child overweight as a health issue was
      high at baseline and increased further after weight feedback. After feedback, the
      proportion of parents that correctly recognised their child was overweight
      increased from 21.9% to 37.7%, and more than a third of parents of overweight
      children sought further information regarding their child's weight. However,
      parent-reported changes in lifestyle behaviours among children were minimal, and
      limited to increases in physical activity in the obese children only. There was
      some suggestion that weight feedback had a greater impact upon changing parental
      recognition of the health risks associated with child overweight in non-white
      ethnic groups. CONCLUSIONS: In this population-based sample of parents of
      children participating in the National Child Measurement Programme, provision of
      weight feedback increased recognition of child overweight and encouraged some
      parents to seek help, without causing obvious unfavourable effects. The impact of
      weight feedback on behaviour change was limited; suggesting that further work is
      needed to identify ways to more effectively communicate health information to
      parents and to identify what information and support may encourage parents in
      making and maintaining lifestyle changes for their child.

PMID- 24888974
TI  - DigiPET: sub-millimeter spatial resolution small-animal PET imaging using thin
      monolithic scintillators.
AB  - A new preclinical PET system based on dSiPMs, called DigiPET, is presented. The
      system is based on thin monolithic scintillation crystals and exhibits superior
      spatial resolution at low-cost compared to systems based on pixelated crystals.
      Current dedicated small-rodent PET scanners have a spatial resolution in the
      order of 1 mm. Most of them have a large footprint, requiring considerable
      laboratory space. For rodent brain imaging, a PET scanner with sub-millimeter
      resolution is desired. To achieve this, crystals with a pixel pitch down to 0.5
      mm have been used. However, fine pixels are difficult to produce and will render
      systems expensive. In this work, we present the first results with a high
      resolution preclinical PET scanner based on thin monolithic scintillators and a
      large solid angle. The design is dedicated to rat-brain imaging and therefore has
      a very compact geometry. Four detectors were placed in a square arrangement with
      a distance of 34.5 mm between two opposing detector modules, defining a field of
      view (FOV) of 32 * 32 * 32 mm(3). Each detector consists of a thin monolithic
      LYSO crystal of 32 * 32 * 2 mm(3) optically coupled to a digital silicon
      photomultiplier (dSiPM). Event positioning within each detector was obtained
      using the maximum likelihood estimation (MLE) method. To evaluate the system
      performance, we measured the energy resolution, coincidence resolving time (CRT),
      sensitivity and spatial resolution. The image quality was evaluated by acquiring
      a hot-rod phantom filled with (18)F-FDG and a rat head one hour after an (18)F
      FDG injection. The MLE yielded an average intrinsic spatial resolution on the
      detector of 0.54 mm FWHM. We obtained a CRT of 680 ps and an energy resolution of
      18% FWHM at 511 keV. The sensitivity and spatial resolution obtained at the
      center of the FOV were 6.0 cps kBq(-1) and 0.7 mm, respectively. In the
      reconstructed images of the hot-rod phantom, hot rods down to 0.7 mm can be
      discriminated. In conclusion, a compact PET scanner was built using dSiPM
      technology and thin monolithic LYSO crystals. Excellent spatial resolution and
      acceptable sensitivity were demonstrated. Promising results were also obtained in
      a hot-rod phantom and in rat-brain imaging. 

PMID- 24888976
TI  - Escalate shamefully, de-escalate angrily or gratefully: the influence of discrete
      emotions on escalation of commitment.
AB  - Decision makers often tend to escalate their commitment when faced with a dilemma
      of whether to continue a losing course of action. Researchers recently began to
      investigate the influence of discrete emotions on this decision tendency.
      However, this work has mainly focused on negative emotions and rarely considered
      positive emotions, to say nothing of comparing the effects of both of them
      simultaneously. The current study addresses this need by presenting the results
      of three experiments that examined the effects of four emotions of both positive
      and negative valences in escalation situations. Experiment 1 investigated the
      relationships of three trait emotions (hope, shame, and anger) and escalation of
      commitment. Experiments 2 and 3 examined the effects of three induced emotions
      (anger, shame, and gratitude) on escalation of commitment in a student sample and
      an employee sample, respectively. The results revealed that the effects of
      discrete emotions in escalation situations are mainly due to their associated
      differences on the appraisal dimension of responsibility that is related to
      escalation situations rather than their valence. The theoretical and practical
      implications are discussed. 

PMID- 24888975
TI  - Effects of small intestinal submucosa content on the adhesion and proliferation
      of retinal pigment epithelial cells on SIS-PLGA films.
AB  - The retinal pigment epithelium (RPE) plays a critical role in the maintenance of
      the normal functions of the retina, particularly the photoreceptors. RPE
      dysfunction, vision loss and degeneration have been implicated as the cause of
      many retinal diseases, including retinitis pigmentosa and age-related macular
      degeneration (AMD). To overcome such disorders, tissue engineering could offer
      useful strategies, using biodegradable polymeric films to replace diseased or
      lost RPE. Synthetic/natural hybrid films have been studied as a temporary
      substrate for growing RPEs in biological implantations. In this study, we
      prepared small intestinal submucosa (SIS)-poly(lactic-co-glycolic) (PLGA) hybrid
      films and seeded human RPE cells (ARPE-19 cells) onto the film surface. We
      investigated the film suitability for RPE cell proliferation by MTT assay. The
      morphology of cellular adhesion on the film was confirmed by scanning electron
      microscopy (SEM). Reverse transcription-polymerase chain reaction (RT-PCR) and 3
      amino-9-ethylcarbazole (AEC) staining were performed to examine mRNA expression
      and to compare cell proliferation on the films, using cytokeratin as a marker of
      RPE. Conclusively, we confirmed the higher cell survival rate and much stronger
      phenotype expression of RPEs on SIS-PLGA films compared to pure PLGA films. These
      results demonstrated the potential application of SIS-PLGA films in tissue
      engineering strategies. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24888973
TI  - Early metabolic development of posteromedial cortex and thalamus in humans
      analyzed via in vivo quantitative magnetic resonance spectroscopy.
AB  - The posteromedial cortex (PMC) including the posterior cingulate, retrosplenial
      cortex, and medial parietal cortex/precuneus is an epicenter of cortical
      interactions in a wide spectrum of neural activity. Anatomic connections between
      PMC and thalamic components have been established in animal studies, but similar
      studies do not exist for the fetal and neonatal period. Magnetic resonance
      spectroscopy (MRS) allows for noninvasive measurement of metabolites in early
      development. Using single-voxel 3-T MRS, healthy term neonates (n = 31, mean
      postconception age 41.5 weeks +/- 3.8 weeks) were compared with control children
      (n = 23, mean age 9.4 years +/- 5.1 years) and young adults (n = 10, mean age
      24.1 years +/- 2.6 years). LCModel-based calculations compared metabolites within
      medial parietal gray matter (colocalizing to the PMC), posterior thalamus, and
      parietal white matter voxels. Common metabolic changes existed for neuronal
      axonal maturation and structural markers in the PMC, thalamus, and parietal white
      matter with increasing NAA and glutamate and decreasing myoinositol and choline
      with age. Key differences in creatine and glucose metabolism were noted in the
      PMC, in contrast to the thalamic and parietal white matter locations, suggesting
      a unique role of energy metabolism. Significant parallel metabolite developmental
      changes of multiple other metabolites including aspartate, glutamine, and
      glutathione with age were present between PMC and parietal white matter but not
      between PMC and thalamus. These findings offer insight into the metabolic
      architecture of the interface between structural and functional topology of brain
      networks. Further investigation unifying metabolic changes with functional and
      anatomic pathways may further enhance the understanding of the PMC in posterior
      default mode network development.

PMID- 24888978
TI  - Partially Biodegradable Distraction Implant to Replace Conventional Implants in
      Alveolar Bone of Insufficient Height: A Preliminary Study in Dogs.
AB  - BACKGROUND: Dental implants have been widely used in the last few decades.
      However, patients with insufficient bone height need reconstructive surgeries
      before implant insertion. The distraction implant (DI) has been invented to
      simplify the treatment procedure, but the shortcomings of DIs have limited their
      clinical use. We incorporated biodegradable polyester into a novel DI called the
      partially biodegradable distraction implant (PBDI). PURPOSE: The purpose of this
      study was to assess the radiological, histological, and biomechanical properties
      of the PBDI in animal models. MATERIAL AND METHODS: PBDIs were manufactured and
      inserted into the atrophied mandibles of nine dogs. Box-shaped alveolar bones
      were segmented and distracted. The dogs were randomly divided into three groups
      that were sacrificed 1, 2, and 3 months after the implant insertion. Actual
      augmentation height (AAH) of the bone segments was measured to evaluate the
      effect of distraction. X-ray examination and micro-CT reconstruction and analysis
      were used to evaluate the regenerated bone in the distraction gap and bone around
      the functional element. Histological sections were used to evaluate the
      osseointegration and absorption of the PBDI. Fatigue tests were used to evaluate
      the biomechanical properties of the PBDI. RESULTS: Little change was found in AAH
      among the three groups. X-ray examination and micro-CT reconstruction showed good
      growth of regenerated bone in the distraction gap. Alveolar bone volume around
      the functional element increased steadily. No obvious bone absorption occurred in
      the alveolar crest around PBDI. Three months after distraction, the functional
      element achieved osseointegration, and the support element began to be absorbed.
      All PBDIs survived the fatigue test. CONCLUSIONS: The PBDI is a novel and
      reliable dental implant. It becomes a conventional implant after the absorption
      of the support element and the removal of the distraction screw. It is a
      promising replacement for conventional implants in patients with insufficient
      alveolar bone height.

PMID- 24888977
TI  - Orphan/vulnerable child caregiving moderates the association between women's
      autonomy and their BMI in three African countries.
AB  - Enhancement of women's autonomy is a key factor for improving women's health and
      nutrition. With nearly 12 million orphan and vulnerable children (OVC) in Africa
      due to HIV/AIDS, the study of OVC primary caregivers' nutrition is fundamental.
      We investigated the association between married women's autonomy and their
      nutritional status; explored whether this relationship was modified by OVC
      primary caregiving; and analyzed whether decision-making autonomy mediated the
      association between household wealth and body mass index (BMI). This cross
      sectional study used the data from Demographic Health Surveys collected during
      2006-2007 from 20- to 49-year-old women in Namibia (n = 2633), Swaziland (n =
      1395), and Zambia (n = 2920). Analyses included logistic regression, Sobel, and
      Goodman tests. Our results indicated that women's educational attainment
      increased the odds for being overweight (Swaziland and Zambia) and decreased the
      odds for being underweight (Namibia). In Zambia, having at least primary
      education increased the odds for being overweight only among child primary
      caregivers regardless of the OVC status of the child, and having autonomy for
      buying everyday household items increased the odds for being overweight only
      among OVC primary caregivers. Decision-making autonomy mediated the association
      between household wealth and OVC primary caregivers' BMI in Zambia (Z = 2.13, p
      value = 0.03). We concluded that depending on each country's contextual
      characteristics, having education can decrease the odds for being an underweight
      woman or increase the odds for being an overweight woman. Further studies should
      explore why in Namibia education has an effect on women's overweight status only
      among women who are caring for a child. 

PMID- 24888980
TI  - Evaluation of oestrous detection in dairy cattle comparing an automated activity
      monitoring system to visual observation.
AB  - The objective of the study was to evaluate an automated activity monitoring (AAM)
      system for oestrous detection in dairy cows. Specifically, we set out to
      determine the oestrous detection efficiency and accuracy of the AAM system and to
      compare reproductive performance of cows detected either by AAM, by visual
      observation (VO) or by at least 1 of the 2 methods (EOM). A total of 1004
      potential cow-periods from 348 cows were analysed. Oestrous detection rates (EDR)
      were calculated for 21 day (VWP+21), 42 day (VWP+42), and 63 day (VWP+63) after
      voluntary waiting period (VWP). Oestrous detection rate did not differ between
      AAM (42.1%) and VO (37.3%) during VWP+21 (p > 0.05) but was significantly higher
      in EOM (56.3%, p < 0.05). Oestrous detection by AAM achieved an efficiency
      (number of correctly detected oestruses/total number of cow-periods*100) of 35.6%
      and an accuracy (number of correctly detected oestruses/(number of true+ false
      oestruses)*100) of 83.8%. Visual observation resulted in an efficiency of 34.3%
      and accuracy of 75.1%. Pregnancy rate at 200 DIM was higher in AAM (66.8%) and
      EOM (68.8%) than in VO (57.1%, p < 0.05). Cows detected by AAM (p < 0.05) showed
      a 1.37 times greater risk to conceive than cows detected by VO as the reference
      (p < 0.05). The results show that an automated activity monitoring system can
      support oestrous detection in dairy cattle. The exclusive use of such a system,
      however, cannot be recommended.

PMID- 24888979
TI  - Discussion of "Combining biomarkers to optimize patient treatment
      recommendation".

PMID- 24888981
TI  - Genetic basis for denitrification in Ensifer meliloti.
AB  - BACKGROUND: Denitrification is defined as the dissimilatory reduction of nitrate
      or nitrite to nitric oxide (NO), nitrous oxide (N2O), or dinitrogen gas (N2). N2O
      is a powerful atmospheric greenhouse gas and cause of ozone layer depletion.
      Legume crops might contribute to N2O production by providing nitrogen-rich
      residues for decomposition or by associating with rhizobia that are able to
      denitrify under free-living and symbiotic conditions. However, there are limited
      direct empirical data concerning N2O production by endosymbiotic bacteria
      associated with legume crops. Analysis of the Ensifer meliloti 1021 genome
      sequence revealed the presence of the napEFDABC, nirK, norECBQD and nosRZDFYLX
      denitrification genes. It was recently reported that this bacterium is able to
      grow using nitrate respiration when cells are incubated with an initial O2
      concentration of 2%; however, these cells were unable to use nitrate respiration
      when initially incubated anoxically. The involvement of the nap, nirK, nor and
      nos genes in E. meliloti denitrification has not been reported. RESULTS: E.
      meliloti nap, nirK and norC mutant strains exhibited defects in their ability to
      grow using nitrate as a respiratory substrate. However, E meliloti nosZ was not
      essential for growth under these conditions. The E. meliloti napA, nirK, norC and
      nosZ genes encode corresponding nitrate, nitrite, nitric oxide and nitrous oxide
      reductases, respectively. The NorC component of the E. meliloti nitric oxide
      reductase has been identified as a c-type cytochrome that is 16 kDa in size.
      Herein, we also show that maximal expression of the E. meliloti napA, nirK, norC
      and nosZ genes occurred when cells were initially incubated anoxically with
      nitrate. CONCLUSION: The E. meliloti napA, nirK, norC and nosZ genes are involved
      in nitrate respiration and in the expression of denitrification enzymes in this
      bacterium. Our findings expand the short list of rhizobia for which
      denitrification gene function has been demonstrated. The inability of E. meliloti
      to grow when cells are initially subjected to anoxic conditions is not
      attributable to defects in the expression of the napA, nirK, norC and nosZ
      denitrification genes.

PMID- 24888982
TI  - Engineering human tumour-associated chromosomal translocations with the RNA
      guided CRISPR-Cas9 system.
AB  - Cancer-related human chromosomal translocations are generated through the
      illegitimate joining of two non-homologous chromosomes affected by double-strand
      breaks (DSB). Effective methodologies to reproduce precise reciprocal tumour
      associated chromosomal translocations are required to gain insight into the
      initiation of leukaemia and sarcomas. Here we present a strategy for generating
      cancer-related human chromosomal translocations in vitro based on the ability of
      the RNA-guided CRISPR-Cas9 system to induce DSBs at defined positions. Using this
      approach we generate human cell lines and primary cells bearing chromosomal
      translocations resembling those described in acute myeloid leukaemia and Ewing's
      sarcoma at high frequencies. FISH and molecular analysis at the mRNA and protein
      levels of the fusion genes involved in these engineered cells reveal the
      reliability and accuracy of the CRISPR-Cas9 approach, providing a powerful tool
      for cancer studies. 

PMID- 24888983
TI  - An enhanced biometric authentication scheme for telecare medicine information
      systems with nonce using chaotic hash function.
AB  - Recently, Awasthi and Srivastava proposed a novel biometric remote user
      authentication scheme for the telecare medicine information system (TMIS) with
      nonce. Their scheme is very efficient as it is based on efficient chaotic one-way
      hash function and bitwise XOR operations. In this paper, we first analyze Awasthi
      Srivastava's scheme and then show that their scheme has several drawbacks: (1)
      incorrect password change phase, (2) fails to preserve user anonymity property,
      (3) fails to establish a secret session key beween a legal user and the server,
      (4) fails to protect strong replay attack, and (5) lacks rigorous formal security
      analysis. We then a propose a novel and secure biometric-based remote user
      authentication scheme in order to withstand the security flaw found in Awasthi
      Srivastava's scheme and enhance the features required for an idle user
      authentication scheme. Through the rigorous informal and formal security
      analysis, we show that our scheme is secure against possible known attacks. In
      addition, we simulate our scheme for the formal security verification using the
      widely-accepted AVISPA (Automated Validation of Internet Security Protocols and
      Applications) tool and show that our scheme is secure against passive and active
      attacks, including the replay and man-in-the-middle attacks. Our scheme is also
      efficient as compared to Awasthi-Srivastava's scheme. 

PMID- 24888984
TI  - Development of a decision support engine to assist patients with hospital
      selection.
AB  - Hospital selection is a complicated decision-making process. Although patients
      have expressed greater desire to participate in decision-makings of their
      healthcare, it can be problematic for them to accumulate large amount of
      information and using it for making an optimal choice in hospital selection. The
      aim of this research is to develop a decision engine for hospital selection
      (DEHS) to support patients while accessing healthcare resources. DEHS applied the
      analytic hierarchy process and the geographic information system to aggregate
      different decision factors and spatial information. The results were evaluated
      through investigating the consistency of the preferences that users inputted, the
      degree that the results match patient choices, the satisfactions of users, and
      the helpfulness of the results. Data were collected for 3 months. One hundred and
      four users visited DEHS and 85.5 % of them used DEHS more than once.
      Recommendations of the institutes (36 %) was ranked as the primary decision
      factor that most users concerned. Sixty-seven percent of the sessions searched
      for hospitals and 33 % for clinics. Eighty-eight percent of the results matched
      the choices of patients. Eighty-three percent of the users agreed that the
      suggested results were satisfactory, and 70 % agreed that the information were
      helpful. The DEHS provides the patients with simple measurements and
      individualized list of suggested medical institutes, and allows them to make
      decisions based on credible information and consults the experiences of others at
      the same time. The suggested results were considered satisfactory and helpful. 

PMID- 24888986
TI  - Cleavage of unactivated amide bonds by ammonium salt-accelerated hydrazinolysis.
AB  - Hydrazinolysis of unactivated amide bonds is significantly accelerated by the
      addition of ammonium salts. The reactions proceed at 50-70  degrees C to give
      amines with broad substrate scope that outperforms existing amide bond cleavage
      reactions. Application to peptide and amino sugar derivatives is also
      demonstrated. 

PMID- 24888985
TI  - Trauma exposure is associated with increased context-dependent adjustments of
      cognitive control in patients with posttraumatic stress disorder and healthy
      controls.
AB  - Recent evidence has suggested that posttraumatic stress disorder (PTSD) is
      associated with alterations in prefrontal-cortex-dependent cognitive processes
      (e.g., working memory, cognitive control). However, it remains unclear whether
      these cognitive dysfunctions are related to PTSD symptomatology or trauma
      exposure. Furthermore, regarding cognitive control, research has only focused on
      the integrity of selected control functions, but not their dynamic regulation in
      response to changing environmental demands. Therefore, the present study
      investigated dynamic variations in interference control, in addition to overall
      interference susceptibility and working memory (WM) performance in matched groups
      of 24 PTSD patients and 26 traumatized and 30 nontraumatized healthy controls.
      The Simon task was used to measure overall interference susceptibility and the
      flexible adjustment of cognitive control, on the basis of the occurrence of
      response conflicts (conflict adaptation effect). WM performance was assessed with
      the forward and backward digit span tasks. Since we have previously shown that
      trauma exposure per se is associated with reduced hair cortisol concentrations
      (HCC), we further explored whether PTSD/trauma-related cognitive alterations are
      related to HCC in proximal 3-cm hair segments. The results revealed that PTSD
      patients and traumatized controls showed significantly more pronounced conflict
      adaptation effects than nontraumatized controls. Moreover, the conflict
      adaptation effect was positively related to the number of lifetime traumatic
      events and the frequency of traumatization. The groups did not differ in overall
      interference susceptibility or WM performance. Exploratory analyses revealed no
      association between HCC and the observed cognitive differences. These results
      suggest that context-driven control adjustments constitute a sensitive correlate
      of trauma exposure, irrespective of PTSD.

PMID- 24888987
TI  - Segmental versus extended resection for sporadic colorectal cancer in young
      patients.
AB  - BACKGROUND AND OBJECTIVES: Guidelines on the management of colon cancer state
      that extensive colectomy should be "considered" for patients of young age (<50).
      This study aimed to compare the risk of metachronous cancer, overall recurrence
      and mortality between segmental and extended colon resections in patients under
      the age of 50 with sporadic CRC. METHODS: We performed a retrospective review of
      patients age <50 undergoing surgery for CRC from 1991 to 2009. Patients were
      divided into two groups based on extent of resection: segmental versus extended.
      The primary outcomes analyzed were metachronous tumors, disease recurrence, and
      overall survival. RESULTS: Two hundred seventy one patients underwent segmental
      resection and 30 underwent extended resection. 3.3% in the segmental resection
      group developed metachronous CRC versus 0% in the extended resection group (P =
      0.61). There was no significant difference in the risk of recurrence or mortality
      for those who underwent a segmental resection compared to those with an extended
      resection. In a regression model, type of surgery was not an independent risk
      factor for recurrence or mortality. CONCLUSIONS: Extended colectomy for sporadic
      CRC in patients younger than 50 does not improve disease-free or overall
      survival. Further study to determine if segmental resection is appropriate
      oncologic treatment is warranted.

PMID- 24888988
TI  - Pillar[5]arene-mediated synthesis of gold nanoparticles: size control and sensing
      capabilities.
AB  - We present a simple procedure for the synthesis of quasi-spherical Au
      nanoparticles in a wide size range mediated by macrocyclic host molecules,
      ammonium pillar[5]arene (AP[5]A). The strategy is based on a seeded growth
      process in which the water-soluble pillar[5]arene undergoes complexation of the
      Au salt through the ammonium groups, thereby avoiding Au nucleation, while acting
      as a stabilizer. The presence of the pillar[5]arene onto the Au nanoparticle
      particle surface is demonstrated by surface-enhanced Raman scattering (SERS)
      spectroscopy, and the most probable conformation of the molecule when adsorbed on
      the Au nanoparticles surface is suggested on the basis of theoretical
      calculations. In addition, we analyze the host-guest interactions of the AP[5]A
      with 2-naphthoic acid (2NA) by using (1)H NMR spectroscopy and the results are
      compared with theoretical calculations. Finally, the promising synergetic effects
      of combining supramolecular chemistry and metal nanoparticles are demonstrated
      through SERS detection in water of 2NA and a polycyclic aromatic hydrocarbon,
      pyrene (PYR).

PMID- 24888989
TI  - Nuchal fibrolipoma gives rugby players the 'hump'.

PMID- 24888990
TI  - Neonicotinoid concentrations in arable soils after seed treatment applications in
      preceding years.
AB  - BACKGROUND: Concentrations of the neonicotinoid insecticides clothianidin,
      thiamethoxam and imidacloprid were determined in arable soils from a variety of
      locations in England. RESULTS: In soil samples taken from the central area of
      fields, concentrations of clothianidin ranged from 0.02 to 13.6 ug kg(-1) .
      Thiamethoxam concentrations were between <0.02 and 1.50 ug kg(-1) , and
      imidacloprid concentrations between <0.09 and 10.7 ug kg(-1) . Concentrations of
      clothianidin and thiamethoxam were lower in soil samples taken from the edges of
      fields than from the centres of fields, but this difference was less pronounced
      for imidacloprid. CONCLUSION: This work gives a clear indication of the levels of
      neonicotinoids in arable soils after typical use of these compounds as seed
      dressings in the United Kingdom. There was evidence that imidacloprid was more
      persistent in the soils studied than clothianidin and thiamethoxam. As
      clothianidin and thiamethoxam have largely superseded imidacloprid in the United
      Kingdom, neonicotinoid levels were lower than suggested by predictions based on
      imidacloprid alone.

PMID- 24888991
TI  - Association between dopamine beta-hydroxylase 19-bp insertion/deletion
      polymorphism and major depressive disorder.
AB  - Norepinephrine and dopamine mediate important aspects of several psychoses,
      including major depressive disorder (MDD). Dopamine beta-hydroxylase (DBH)
      catalyzes the conversion of dopamine to norepinephrine in central neurons and
      thus is critically involved in maintaining the transformational homeostasis.
      Functional polymorphisms have been reported in DBH gene, including a 19-bp
      insertion/deletion polymorphism (DBH5'-insertion/deletion (Ins/Del)) and a single
      nucleotide polymorphism (-1021C/T). The purpose of this study was to investigate
      whether there was an association between the two functional polymorphisms and MDD
      in a Han Chinese population. DBH5'-Ins/Del and -1021C/T polymorphism in promoter
      region of DBH gene was analyzed in 313 patients with MDD and 318 healthy subjects
      by using polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP) analysis. The results showed statistically significant
      associations for genotypic distribution between the DBH5'-Ins/Del polymorphism
      and MDD (P = 0.007). Individuals with Del/Del genotype demonstrated a 1.72 times
      increased risk of MDD compared to those with insertion alleles (95% confidence
      interval (CI) 1.20-2.47, P = 0.003). Moreover, the Del/Del genotype was
      associated with poorer digital span and language scores than the insertion
      alleles in healthy subjects (P = 0.041 and P = 0.048, respectively). However,
      there was no association observed between the genotype and allele frequencies for
      -1021C/T and depression. Our data suggest that the DBH5'-Ins/Del polymorphism of
      the DBH gene may be associated with susceptibility to MDD in a Chinese
      population.

PMID- 24888993
TI  - Antimicrobial activity of selected Iranian medicinal plants against a broad
      spectrum of pathogenic and drug multiresistant micro-organisms.
AB  - The antimicrobial activities of 44 methanolic extracts from different parts of
      Iranian indigenous plant species used in traditional medicines of Iran were
      tested against a panel of 35 pathogenic and multiresistant bacteria and 1 yeast.
      The antimicrobial efficacy was determined using Muller-Hinton agar in Petri
      dishes seeded by a multiple inoculator and minimal inhibition concentration (MIC)
      method. The 21 most active extracts (MIC < 0.3 mg ml(-1) for one or several micro
      organisms) were submitted to a more refined measurement. The best antibacterial
      activity was obtained by 10 plants. Microdilution assays allowed to determinate
      the MIC and MBC of the 21 most active extracts. The lowest achieved MIC value was
      78 MUg ml(-1), with 4 extracts. This work confirms the antimicrobial activity of
      assayed plants and suggests further examination to identify the chemical
      structure of their antimicrobial compounds. Significance and impact of the study:
      This study describes the antimicrobial screening of Iranian plant extracts chosen
      according to traditional practice against 36 microbial strains, from reference
      culture collections or recent clinical isolates, and enables to select 4
      candidates for further chemical characterization and biological assessment:
      Dorema ammoniacum, Ferula assa-foetida, Ferulago contracta (seeds) and Perovskia
      abrotanoides (aerial parts). This may be useful in the development of potential
      antimicrobial agents, from easily harvested and highly sustainable plant parts.
      Moreover, the weak extent of cross-resistance between plant extracts and
      antibiotics warrants further research and may promote a strategy based on less
      potent but time-trained products.

PMID- 24888994
TI  - Hemi-spectrum substitution after water signal fitting (HESWAF): an improvement of
      the modulus post-processing of MR spectra.
AB  - OBJECTIVE: In a previous study, we have shown that modulus post-processing is a
      simple and efficient tool to both phase correct and frequency align magnetic
      resonance (MR) spectra automatically. Furthermore, this technique also eliminates
      sidebands and phase distortions. The advantages of the modulus technique have
      been illustrated in several applications to brain proton MR spectroscopy. Two
      possible drawbacks have also been pointed out. The first one is the theoretical
      decrease in signal-to-noise ratio (SNR) by a factor up to ?2 when comparing the
      spectrum obtained after modulus versus conventional post-processing. The second
      pitfall results from the symmetrization of the spectrum induced by modulus post
      processing, since any resonance or artifact located at the left of the water
      resonance is duplicated at the right of the water resonance, thus contaminating
      the region of the spectrum containing the resonances of interest. Herein, we
      propose a strategy in order to eliminate these two limitations. MATERIALS AND
      METHODS: Concerning the SNR issue, two complementary approaches are presented
      here. The first is based on the application of modulus post-processing before
      spatial apodization, and the second consists in substituting the left half of the
      spectrum by the fit of the water resonance before applying modulus post
      processing. The symmetrization induced by modulus post-processing then combines
      the right half of the original spectrum containing the resonances of interest
      with the left half of the water fit, free of noise and artifacts. Consequently,
      the SNR is improved when compared to modulus post-processing alone. As a bonus,
      any artifact or resonance present in the left half of the original spectrum is
      removed. This solves the second limitation. RESULTS: After validation of the
      technique on simulations, we demonstrated that this improvement of the modulus
      technique is significantly advantageous for both in vitro and in vivo
      applications. CONCLUSION: By improving the SNR of the spectra and eliminating
      eventual contaminations, the new strategies proposed here confer an additional
      competitive advantage to the modulus post-processing technique.

PMID- 24888995
TI  - Factors affecting metacognition of undergraduate nursing students in a blended
      learning environment.
AB  - This paper is a report of a study to examine the influence of demographic,
      learning involvement and learning performance variables on metacognition of
      undergraduate nursing students in a blended learning environment. A cross
      sectional, correlational survey design was adopted. Ninety-nine students invited
      to participate in the study were enrolled in a professional nursing ethics course
      at a public nursing college. The blended learning intervention is basically an
      assimilation of classroom learning and online learning. Simple linear regression
      showed significant associations between frequency of online dialogues, the Case
      Analysis Attitude Scale scores, the Case Analysis Self Evaluation Scale scores,
      the Blended Learning Satisfaction Scale scores, and Metacognition Scale scores.
      Multiple linear regression indicated that frequency of online dialogues, the Case
      Analysis Self Evaluation Scale and the Blended Learning Satisfaction Scale were
      significant independent predictors of metacognition. Overall, the model accounted
      for almost half of the variance in metacognition. The blended learning module
      developed in this study proved successful in the end as a catalyst for the
      exercising of metacognitive abilities by the sample of nursing students. Learners
      are able to develop metacognitive ability in comprehension, argumentation,
      reasoning and various forms of higher order thinking through the blended learning
      process. 

PMID- 24888992
TI  - Knockdown of PKCepsilon expression inhibits growth, induces apoptosis and
      decreases invasiveness of human glioma cells partially through Stat3.
AB  - Glioma is the most common primary central nervous system tumor. Despite
      considerable research effort, little progress has been made in the therapeutic
      treatment of this disease. Protein kinase Cepsilon (PKCepsilon), an important
      intracellular signaling molecule, modulates diverse cellular functions, including
      cell proliferation, apoptosis, invasion and differentiation. The aim of the study
      is to investigate whether knockdown of PKCepsilon expression by RNA interference
      (RNAi) could affect the growth, apoptosis and invasion of human glioma cells, and
      the involvement of the signal transducer and activator of transcription 3 (Stat3)
      signaling pathway in these effects. Our data showed that knockdown of PKCepsilon
      expression inhibited proliferation, induced apoptosis and decreased invasiveness
      of human glioma cell lines U251 and U87, as well as suppressed the growth of U87
      cell-derived tumors in nude mice. Moreover, PKCepsilon physically interacts with
      Stat3, and knockdown of PKCepsilon expression attenuated Stat3Ser727
      phosphorylation and B-cell lymphoma-extra large (Bcl-xL) expression in the two
      human glioma cell lines. These results support an important role for PKCepsilon
      in glioma cell growth, apoptosis and invasion, and PKCepsilon exerting its above
      effects at least in part through Stat3. Thus, PKCepsilon has the potential to be
      an attractive therapeutic target for glioma therapy. 

PMID- 24888996
TI  - Difference in perception between nurses and patients related to patients' health
      locus of control.
AB  - Patient's health locus of control (HLOC) belief associates with superior health
      outcomes and patient satisfaction. Higher levels of HLOC beliefs among patients
      and nurses contribute positively in developing the partnership model of care. The
      purpose of this study was to examine the differences between nurses and patients'
      perception of patient's health locus of control at the Jordanian general health
      care settings. This study used cross-sectional, descriptive-correlation design to
      collect data using self-report questionnaires from 180 general nurses and 178
      patients in general wards. Data collected were in regard to patient's perception
      of health locus of control. Patients and nurses expressed high level of
      externality and internality HLOC beliefs inferring the significance of
      partnership model of care. Chance was rated low among nurses and patients. The
      study emphasizes the role of nurses in enhancing their patient control and power
      over their health and participation in planning and implementation of health-care
      plans. 

PMID- 24888997
TI  - Towards patient-centred care: perspectives of nurses and midwives regarding shift
      to-shift bedside handover.
AB  - The aim of this descriptive qualitative study was to explore perspectives of
      nurses and midwives towards the introduction of shift-to-shift bedside handover.
      Semistructured interviews with nurses (n = 20) and midwives (n = 10) occurred 12
      months after the introduction of bedside handover. Data were analyzed using
      thematic content analysis. Two main themes were identified: enhanced individual
      patient care and documentation, along with improved patient-clinician
      partnerships; and protection of confidentiality and privacy. The newly introduced
      bedside handover model improved efficiency and accuracy of the handover process
      and led to the provision of safe, high-quality care. Development of ward-specific
      tools and relevant educational resources, along with clinical support, are
      identified as the facilitators to ensure the new model can be successfully
      integrated into normal clinical practice.

PMID- 24888998
TI  - Evaluation of interrater reliability assessing oral health in acute care
      settings.
AB  - Oral health is increasingly important in relation to illness prevention,
      treatment and rehabilitation. The aim of this study was to test interrater
      reliability nurses in-between of Revised Oral Assessment Guide (ROAG) among
      patients acutely admitted to hospital with a medical condition. All patients were
      assessed twice. Percent agreement and Cohen's Kappa coefficient was calculated.
      Substantial differences were found between observers' ratings. If ROAG is to be
      implemented, it must be preceded for example by specific education, visual
      guidance or selection of most important elements in the screening tool. 

PMID- 24888999
TI  - Impact of psychosocial status and disease knowledge on deferoxamine adherence
      among thalassaemia major adolescents.
AB  - This cross-sectional study aimed to explore the relationship between psychosocial
      status, disease knowledge and adherence to deferoxamine treatment in adolescents
      with thalassaemia major. A purposive sample of 36 adolescents with transfusion
      dependence, ages 12-19 years, was recruited. A semi-structured interview and two
      structured questionnaires were used. In this sample, 56% were low adherence and
      36% were psychologically impaired. Statistically significant factors associated
      with psychological impairment were: adolescents more than 16 years; low
      deferoxamine adherence; mean ferritin more than 2500 MUg/L; family size more than
      six; family income equal or less than 350 Jordanian dinar and having sibling with
      thalassaemia. Additionally, adolescents with high level of knowledge had
      significantly lower scores on Pediatric Symptom Checklist.

PMID- 24889000
TI  - The efficacy of education programme for preventing constipation in women.
AB  - This study was performed to evaluate the efficiency of the education programme
      for prevention of constipation in women. This study was performed as a pre-test
      posttest design. Thirty-five women were included who have constipation problem.
      Data were collected by questionnaire: Constipation Severity Instrument (CSI),
      Constipation Visual Analogue Scale (CVAS) and Bristol Stool Chart (BSC). Eight
      home visits were made for each of the women and they were followed up for 3
      months. Participants received an individual education programme that included
      advice on dietary consumption such as pulpy-fibrous nutrient consumption, fluid
      intake, an exercise regime and counselling about optimal position to defecate.
      The subscales of 'Colonic Inertia' and 'Pain', and CSI total mean scores and CVAS
      mean scores were decreased significantly after education programme (P < 0.05).
      According to the BSC, 71.5% of the women stated their stool form to be 'sausage
      shaped, but lumpy' before the education programme, but after the said programme
      the percentage had dropped to 17.1%. Education programme given to women who had
      constipation were determined to have been effective in alleviating constipation.
      Nurses should develop appropriate and effective strategies to help women prevent
      constipation.

PMID- 24889001
TI  - The use of cognitive reappraisal and humour as coping strategies for bullied
      nurses.
AB  - This article explores the repercussions of workplace bullying on nurses and the
      health-care profession as a whole. I discuss the nature of workplace bullying and
      draw upon prior studies to explore some of the barriers that prevent witnesses to
      bullying from intervening, as well as barriers faced by targets in taking action
      to stop the bullying. As overt forms of resistance are often not feasible in
      situations where nurses occupy subordinate positions to their bullies, I propose
      that cognitive reappraisal can be an effective coping strategy, and situate this
      perspective within the research on humour, hope and optimism. 

PMID- 24889002
TI  - Non-family support for breastfeeding maintenance among career women in Taiwan: a
      qualitative study.
AB  - The purpose of the study was to describe the influence of non-family-based
      support on breastfeeding practices among career women in Taiwan during the first
      four postnatal months. A qualitative, case study approach was used to investigate
      the phenomenon. A purposive sample of 14 women was recruited and took part in two
      to three in-depth interviews. The data were transcribed and analysed using
      descriptive content analysis. It was found that non-family supports had
      significant influence on their efforts to maintain breastfeeding. Women faced a
      number of challenges to breastfeeding. The services provided by in-centre care
      organizations, the resources and organizations accessed through the Internet, and
      the support provided by colleagues in their workplaces supported women's efforts
      to maintain breastfeeding. Given the low breastfeeding maintenance rates in
      Taiwan and the changing societal structure where fewer families rely on family
      support, the findings highlight the resources, programmes and nursing practice
      which might support women's needs and promote breastfeeding among career women. 

PMID- 24889003
TI  - Kurdish women's preference for mode of birth: a qualitative study.
AB  - Choosing between a normal delivery and Caesarean section is a matter of critical
      importance for a pregnant woman. The third trimester is the time for her to think
      about methods of delivery. The study aims to gain insight into Kurdish pregnant
      women's birth preference and their perception of factors influencing this choice.
      In this qualitative study, 22 pregnant Kurdish women were interviewed during the
      third trimester of their pregnancies. The setting for the study included three
      public health-care centres of Kurdistan University of Medical Sciences in
      Sanandaj, a centre of the Kurdistan province at the western part of Iran. Study
      participants were recruited from maternity units of health-care centres. A
      purposive sample was used initially and then theoretical sampling was used
      towards the end of the data analysis. Sample size was not predetermined but was
      determined when interviewing reached saturation, that is, when no new data
      emerged about categories. The sample size was restricted to 22, as no new data
      were generated after the 20th interview. The criteria required for inclusion in
      the study were being Kurdish women, being in the third trimester of pregnancy, no
      physical disability, no history of Caesarean section and interest in the study. A
      qualitative design was chosen, as it is particularly suited to studying complex
      phenomena or processes that are less understood. This study revealed that of the
      22 participants, 18 preferred vaginal delivery and only four preferred Caesarean
      section. The reasons for choosing the vaginal delivery method were grouped into
      four categories: safety of baby, fear, previous experience and social support.
      This finding does not support the rate of Caesarean section among Kurdish women
      in Sanandaj. It might reflect the effect of other factors such as social,
      institutional, professional and quality of care on women's choice for delivery
      method. 

PMID- 24889004
TI  - An analysis of the cultural problems encountered during caregiving by the nurses
      working in two different regions of Turkey.
AB  - The aim of this study was to identify the cultural problems encountered during
      caregiving by the nurses working in two university hospitals located in western
      and eastern Turkey. This descriptive, comparative study was conducted between
      July 2008 and October 2009 with 338 nurses who volunteered to take part in the
      study. The study data were collected using an individual description
      questionnaire consisting of 10 questions and another questionnaire consisting of
      14 questions to identify the cultural problems encountered by nurses when giving
      care. The study showed with respect to training received on transcultural nursing
      that only 59 nurses had this training, but the percentage was higher in the
      nurses working at the hospital in the west (54.2%) (P > 0.05). It was found that
      a large number of nurses in the sample group (n = 286) gave care to at least one
      individual from another culture, but the percentage was significantly higher in
      the nurses working in the west (56.7%) than in the nurses working in the east
      (43.3%) (P < 0.05). When the problems experienced by the nurses during caregiving
      because of cultural characteristics of patients were explored, it was found that
      they experienced problems mostly in 'communication', and the percentage of those
      having problems was higher in the nurses working in the west (60.8%) (P > 0.05).
      The problem experienced in this area was mostly because of the fact that patients
      'did not speak Turkish' (63.8%). In conclusion, the nurses gave care to patients
      from different cultures, and most of them had trouble when giving care to
      patients from different cultures.

PMID- 24889005
TI  - Validity and reliability of Turkish version of family satisfaction in the
      intensive care unit.
AB  - To evaluate the quality of care that is provided in intensive care units, needs
      and satisfaction of the patient relatives must also be considered. The aim of the
      study is to test the Turkish version of the Family Satisfaction in the Intensive
      Care Unit (FS-ICU-24) Survey, which was developed by Heyland et al. This study
      was planned and applied as a methodological study. Survey was conducted in the
      intensive care units of a military education and research hospital and a medical
      faculty hospital, department of anaesthesia and reanimation in the capital city
      Ankara of Turkey. Sample of the survey was composed of 120 participants.
      Cronbach's alpha value for the FS-ICU-24 general internal consistency in this
      study was calculated as 0.95 for total scale. In this study, the Turkish version
      of the FS-ICU-24 was found to be reliable and valid with Turkish population.

PMID- 24889006
TI  - The role of motivation and self-efficacy on the practice of health promotion
      behaviours in the overweight and obese middle-aged American women.
AB  - The study investigated the relationship between motivation, self-efficacy and
      demographic variables, and determined if they affect the performance of health
      promotion behaviours in overweight or obese middle-aged American women. The
      sample consisted of middle-aged American women from a small town in Michigan. Two
      groups of women aged 30-65, one with a body mass index (BMI) range of 25-29, and
      the second with a BMI of >= 30, completed the Health Self-Determinism Index, the
      General Self-Efficacy Scale and the Health Promoting Lifestyle Profile-II. Self
      efficacy was found to be a significant predictor in the performance of health
      promoting behaviours in both the overweight and obese participants in this study.
      Motivation was not found to be a significant predictor of performance of health
      promotion behaviours in either participant group. Education was found to be a
      significant predictor of performance of health promotion behaviours in the obese
      participants only. Nurses need to develop effective methods of supporting self
      efficacy in both the overweight and obese middle-aged American women. Nursing
      based research focusing on interventions to improve self-efficacy, as well as
      studies identifying effective educational techniques to improve the practice of
      health promotion behaviours in this population is necessary. Further
      investigation into the effect of motivation and demographics on the performance
      of health promotion behaviours is also needed.

PMID- 24889007
TI  - Does therapeutic intervention in atopic dermatitis normalize epidermal Notch
      deficiency?
AB  - This viewpoint presents a unifying concept for the treatment of atopic dermatitis
      (AD) that is based on the improvement of deficient Notch signalling, which
      appears to represent the fundamental epithelial defect of AD resulting in
      epidermal and immunological barrier dysfunction. One study of AD patients
      demonstrated a marked epidermal deficiency of Notch receptors and several mouse
      models with genetically suppressed Notch signalling exhibit dry skin, signs of
      scratching, skin barrier abnormalities, increased transepidermal water loss and
      Th2 cell-mediated immunological changes closely resembling human AD. Notch
      signalling is critically involved in the differentiation of regulatory T cells,
      in the feedback inhibition of activated innate immunity, in the repression of
      activating protein-1 (AP-1), the regulation of late epidermal differentiation
      associated with filaggrin- and stratum corneum barrier lipid processing, in
      aquaporin 3- and claudin-1 expression and in keratinocyte-mediated release of
      thymic stromal lymphopoietin (TSLP), which promotes Th2-driven immune responses
      with TSLP- and IL-31-mediated stimulation of cutaneous sensory neurons involved
      in the induction of itch. Translational evidence will be provided that all major
      therapeutic regimens employed for the treatment of AD such as glucocorticoids,
      calcineurin inhibitors and UV radiation may converge in the upregulation of
      impaired Notch signalling, the proposed pathogenic defect of AD. 

PMID- 24889009
TI  - An apposition-like compound eye with a layered rhabdom in the small diving beetle
      Agabus japonicus (Coleoptera, Dytiscidae).
AB  - The fine structure of the compound eyes of the adult diving beetle Agabus
      japonicus is described with light, scanning, and transmission electron
      microscopy. The eye of A. japonicus is mango-shaped and consists of about 985
      ommatidia. Each ommatidium is composed of a corneal facet lens, an eucone type of
      crystalline cone, a fused layered rhabdom with a basal rhabdomere, seven retinula
      cells (including six distal cells and one basal cell), two primary pigment cells
      and an undetermined number of secondary pigment cells that are restricted to the
      distalmost region of the eye. A clear-zone, separating dioptric apparatus from
      photoreceptive structures, is not developed and the eye thus resembles an
      apposition eye. The cross-sectional areas of the rhabdoms are relatively large
      indicative of enhanced light-sensitivity. The distal and central region of the
      rhabdom is layered with interdigitating microvilli suggesting polarization
      sensitivity. According to the features mentioned above, we suggest that 1) the
      eye, seemingly of the apposition type, occurs in a taxon for which the clear-zone
      (superposition) eye is characteristic; 2) the eye possesses adaptations to
      function in a dim-light environment; 3) the eye may be sensitive to underwater
      polarized light or linearly water-reflected polarized light.

PMID- 24889008
TI  - The influence of community violence and protective factors on asthma morbidity
      and healthcare utilization in high-risk children.
AB  - We examined the longitudinal effects of community risk and protective factors on
      asthma morbidity and healthcare utilization. Three hundred urban caregivers of
      children with poorly controlled asthma were enrolled in a randomized controlled
      trial testing the effectiveness of a behavioral/educational intervention and
      completed measures of exposure to community violence (ECV), social cohesion (SC),
      informal social control (ISC), child asthma control, child asthma symptom
      days/nights, and healthcare utilization. Latent growth curve modeling examined
      the direct and interaction effects of ECV, SC, and ISC on the asthma outcomes
      over 12 months. Caregivers were primarily the biological mother (92 %), single
      (70 %), and poor (50 % earned less than $10,000). Children were African American
      (96 %) and young (mean age = 5.5 years, SD = 2.2). ECV at baseline was high, with
      24.7 % of caregivers reporting more than two exposures to violence in the
      previous 6 months (M = 1.45, SD = 1.61). Caregiver ECV-predicted asthma-related
      healthcare utilization at baseline (b = 0.19, SE = 0.07, p = 0.003) and 2 months
      (b = 0.12, s.e. = 0.05, p = 0.04). ISC and SC moderated the effect of ECV on
      healthcare utilization. Our findings suggest that multifaceted interventions that
      include strategies to curb violence and foster feelings of cohesion among low
      income urban residents may be needed to reduce asthma-related emergency services.

PMID- 24889010
TI  - "It's not broke, so let's not try to fix it": why patients decline a
      cardiovascular implantable electronic device.
AB  - BACKGROUND: Few patients decline therapy of a cardiovascular implantable
      electronic device (CIED), and little is known about the characteristics or
      reasoning of those who do. Our objective was to describe the reasons why patients
      decline CIED implantation using qualitative methods. METHODS: Qualitative,
      engaging thematic analysis. Three patient focus groups led by two trained
      facilitators and one semi-structured interview guide. RESULTS: Of the 13
      patients, two were women and all were white (median age [range], 65 [44-88]
      years). Five themes emerged: (1) don't mess with a good thing; (2) my health is
      good enough; (3) independent decision making; (4) it's your job, but it's my
      choice; and (5) gaps in learning. Most patients who decline CIEDs are
      asymptomatic. Other reasons to decline included feeling well, enjoying life,
      acceptance of the future, desire to try to improve health through diet and
      exercise, hearing of negative CIED experiences, and unwillingness to take on
      associated risks of CIED implantation. A medical record review showed that
      clinicians understand patients' reasons for declining CIED treatment. However,
      focus group data suggest that gaps in patients' knowledge around the purpose and
      function of CIEDs exist and patients may benefit from targeted education.
      CONCLUSIONS: Patients decline implantation of CIEDs for various reasons. Most
      patients who decline therapy are asymptomatic at the time of their device
      consult. Focus group information show data suggestive that device consultations
      should be enhanced to address gaps in patient learning and confirm knowledge
      transfer. Clinicians should revisit treatment options iteratively.

PMID- 24889014
TI  - The personal financial burden of complications after colorectal cancer surgery.
AB  - BACKGROUND: Patients with colorectal cancer (CRC) may suffer significant economic
      hardship during treatment. Complications are common after surgery for CRC and may
      exacerbate the financial burden of CRC even further. METHODS: Within a population
      based survey of patients with stage III CRC, the authors investigated the effects
      of disease and treatment on personal finances and computed a composite measure of
      financial burden. Correlations were examined between components of financial
      burden and patient-reported postoperative complications using chi-square
      analyses, and Mantel-Haenszel chi-square tend tests were used to evaluate
      correlations between composite financial burden scores and surgical
      complications, controlling for patient characteristics and other factors by using
      multivariable Poisson regression. RESULTS: Among 937 respondents, 224 (24%)
      reported complications after surgery. Those with complications had significantly
      higher composite financial burden (P < .001 for trend): they were more likely to
      spend savings (40% vs 31%; P  = .01), borrow or take loans (18% vs 11%; P =
      .007), fail to make credit card payments (18% vs 11%; P = .005), reduce spending
      for food or clothes (38% vs 27%; P = .001), and decrease recreational activities
      (41% vs 33%; P = .03). They took significantly longer to return to work (P  =
      .009) and were more likely to experience significant worry about finances (61% vs
      52%; P = .01). CONCLUSIONS: Complications after surgery for CRC result in
      significant personal financial consequences as well as morbidity. Financial
      stress impairs quality of life and may prevent adherence to recommended
      treatments. Therefore, patients who suffer complications may require not just
      additional clinical care but also economic support and services.

PMID- 24889015
TI  - Towards a better understanding of the nomenclature used in information-packaging
      efforts to support evidence-informed policymaking in low- and middle-income
      countries.
AB  - BACKGROUND: The growing recognition of the importance of concisely communicating
      research evidence and other policy-relevant information to policymakers has
      underpinned the development of several information-packaging efforts over the
      past decade. This has led to a wide variability in the types of documents
      produced, which is at best confusing and at worst discouraging for those they
      intend to reach. This paper has two main objectives: to develop a better
      understanding of the range of documents and document names used by the
      organizations preparing them; and to assess whether there are any consistencies
      in the characteristics of sampled documents across the names employed to label
      (in the title) or describe (in the document or website) them. METHODS: We
      undertook a documentary analysis of web-published document series that are
      prepared by a variety of organizations with the primary intention of providing
      information to health systems policymakers and stakeholders, and addressing
      questions related to health policy and health systems with a focus on low- and
      middle-income countries. No time limit was set. RESULTS: In total, 109 individual
      documents from 24 series produced by 16 different organizations were included.
      The name 'policy brief/briefing' was the most frequently used (39%) to label or
      describe a document, and was used in all eight broad content areas that we
      identified, even though they did not have obviously common traits among them. In
      terms of document characteristics, most documents (90%) used skimmable formats
      that are easy to read, with understandable, jargon-free, language (80%).
      Availability of information on the methods (47%) or the quality of the presented
      evidence (27%) was less common. One-third (32%) chose the topic based on an
      explicit process to assess the demand for information from policy makers and even
      fewer (19%) engaged with policymakers to discuss the content of these documents
      such as through merit review. CONCLUSIONS: This study highlights the need for
      organizations embarking on future information-packaging efforts to be more
      thoughtful when deciding how to name these documents and the need for greater
      transparency in describing their content, purpose and intended audience.

PMID- 24889016
TI  - Subcortical band heterotopia in rat offspring following maternal
      hypothyroxinaemia: structural and functional characteristics.
AB  - Thyroid hormones (TH) play crucial roles in brain maturation and are important
      for neuronal migration and neocortical lamination. Subcortical band heterotopia
      (SBH) represent a class of neuronal migration errors in humans that are often
      associated with childhood epilepsy. We have previously reported the presence of
      SBH in a rodent model of low level hypothyroidism induced by maternal exposure to
      the goitrogen, propylthiouracil (PTU). In the present study, we report the dose
      response characteristics of this developmental malformation and the connectivity
      of heterotopic neurones with other brain regions, as well as their functionality.
      Pregnant rats were exposed to varying concentrations of PTU through the drinking
      water (0-10 p.p.m.) beginning on gestational day 6 to produce graded levels of TH
      insufficiency. Dose-dependent increases in the volume of the SBH present in the
      corpus callosum were documented in the adult offspring, with a clear presence at
      concentrations of PTU that resulted in minor (< 15%) reductions in maternal serum
      thyroxine as measured when pups were weaned. SBH contain neurones,
      oligodendrocytes, astrocytes and microglia. Monoaminergic and cholinergic
      processes were prevalent and many of the axons were myelinated. Anatomical
      connectivity of SBH neurones to cortical neurones and the synaptic functionality
      of these anatomical connections was verified by ex vivo field potential
      recordings. SBH persisted in adult offspring despite a return to euthyroid status
      on termination of exposure and these offspring displayed an increased sensitivity
      to seizures. Features of this model are attractive with respect to the
      investigation of the molecular mechanisms of cortical development, the
      effectiveness of therapeutic intervention in hypothyroxinaemia during pregnancy
      and the impact of the very modest TH imbalance that accompanies exposure to
      environmental contaminants.

PMID- 24889018
TI  - QuBiLS-MIDAS: a parallel free-software for molecular descriptors computation
      based on multilinear algebraic maps.
AB  - The present report introduces the QuBiLS-MIDAS software belonging to the ToMoCoMD
      CARDD suite for the calculation of three-dimensional molecular descriptors (MDs)
      based on the two-linear (bilinear), three-linear, and four-linear (multilinear or
      N-linear) algebraic forms. Thus, it is unique software that computes these tensor
      based indices. These descriptors, establish relations for two, three, and four
      atoms by using several (dis-)similarity metrics or multimetrics, matrix
      transformations, cutoffs, local calculations and aggregation operators. The
      theoretical background of these N-linear indices is also presented. The QuBiLS
      MIDAS software was developed in the Java programming language and employs the
      Chemical Development Kit library for the manipulation of the chemical structures
      and the calculation of the atomic properties. This software is composed by a
      desktop user-friendly interface and an Abstract Programming Interface library.
      The former was created to simplify the configuration of the different options of
      the MDs, whereas the library was designed to allow its easy integration to other
      software for chemoinformatics applications. This program provides functionalities
      for data cleaning tasks and for batch processing of the molecular indices. In
      addition, it offers parallel calculation of the MDs through the use of all
      available processors in current computers. The studies of complexity of the main
      algorithms demonstrate that these were efficiently implemented with respect to
      their trivial implementation. Lastly, the performance tests reveal that this
      software has a suitable behavior when the amount of processors is increased.
      Therefore, the QuBiLS-MIDAS software constitutes a useful application for the
      computation of the molecular indices based on N-linear algebraic maps and it can
      be used freely to perform chemoinformatics studies.

PMID- 24889017
TI  - Variability in the carbon isotope fractionation of trichloroethene on its
      reductive dechlorination by vitamin B12.
AB  - Stable carbon isotope fractionation through the reductive dechlorination of
      trichloroethylene by vitamin B12 was determined to assess the possibility of
      using stable carbon isotope analysis to determine the efficacy of remediation of
      trichloroethylene using vitamin B12. We elucidated the effects of environmental
      conditions, including the pH, reaction temperature, and vitamin B12
      concentration, on the carbon isotope enrichment factor (epsilon). The epsilon
      values were relatively insensitive to the reaction temperature and vitamin B12
      concentration, ranging from -15.70/00 to -16.20/00, with a mean of -15.9 +/-
      0.20/00, at different temperatures and vitamin B12 concentrations. Such a
      reproducible epsilon value could be particularly useful for estimating the extent
      of degradation in reactions in which a mass balance is difficult to achieve.
      However, changing the initial solution pH from 6.5 to 9.0 caused a notable change
      in the epsilon values, from -14.00/00 to -18.00/00. Reactions were investigated
      by calculating the apparent kinetic isotope effects for carbon, which, at 1.029
      1.037, were smaller than the kinetic isotope effect values previously found for C
      Cl bond cleavage. This indicates that a reaction other than the elimination of
      chloride may be a competitive degradation pathway. The dominant degradation
      pathway may be different for different initial solution pH values, and this will
      clearly influence carbon isotope fractionation. Therefore, if the epsilon value
      varies with reaction conditions, such as the solution pH, the calculations should
      take into account the actual environmental conditions that affect the rate
      limiting pathways.

PMID- 24889020
TI  - Sleep-disordered breathing in pregnancy: a brief summary of current knowledge.

PMID- 24889019
TI  - Objective classification of nose-lip-chin profiles and their relation to
      dentoskeletal traits.
AB  - OBJECTIVES: To objectively classify the nose-lip-chin profiles of adult women and
      identify any associations between the nose-lip-chin profile patterns and
      dentoskeletal patterns. SETTING AND SAMPLE POPULATION: Lateral facial photographs
      and lateral cephalograms were obtained for 229 Japanese women who were being
      assessed for orthodontic treatment. METHODS: A feature vector that was effective
      in distinguishing differences in nose-lip-chin profiles was extracted for each
      photograph. To categorize the records into an optimum number of subclasses
      according to nose-lip-chin profile configurations, a vector quantization method
      was applied to the feature vectors of all samples. Dentoskeletal patterns that
      corresponded to the nose-lip-chin profile subclasses were compared. RESULTS:
      Eight profile patterns were identified, and the differences among patterns were
      notably maximized by the nasolabial angle, configuration and vertical length of
      the subnasal region, vertical thickness of the lip vermilion borders, sagittal
      position of the upper- and lower-lip vermilion borders and their relation to each
      other, labiomental angle, depth of the labiomental sulcus, degree of prominence
      of the chin, and degree of protrusion of the mandible. The dentoskeletal patterns
      showed significant differences between the classified profile patterns (p <
      0.01). CONCLUSIONS: A method to objectively classify the nose-lip-chin profiles
      of adult women was established, and the nose-lip-chin profile patterns were found
      to be associated with the dentoskeletal patterns.

PMID- 24889021
TI  - The prefrontal dysfunction in individuals with Internet gaming disorder: a meta
      analysis of functional magnetic resonance imaging studies.
AB  - With the advancement in high-resolution magnetic resonance imaging (MRI)
      technology and automated analysis, studies on functional MRI (fMRI) made it
      possible to identify the functional activity of brain in vivo in individuals with
      Internet gaming disorder (IGD), and to explore the underpinning neuroscience
      basis of IGD. Yet, no available literature has systemically reviewed the fMRI
      studies of IGD using meta-analyses. This study reviewed 61 candidate articles and
      finally selected 10 qualified voxel-wise whole-brain analysis studies for
      performing a comprehensive series of meta-analyses employing effect size signed
      differential mapping approach. Compared with healthy controls, subjects with IGD
      showed a significant activation in the bilateral medial frontal gyrus (MFG) and
      the left cingulate gyrus, as well as the left medial temporal gyrus and fusiform
      gyrus. Furthermore, the on-line time of IGD subjects was positively correlated
      with activations in the left MFG and the right cingulated gyrus. These findings
      implicate the important role of dysfunctional prefrontal lobe in the
      neuropathological mechanism of IGD. Considering the overlapped role of prefrontal
      lobe in the reward and self-regulatory system, our results provided supportive
      evidence for the reclassification of IGD as a behavioural addiction. 

PMID- 24889023
TI  - Images of intravitreal objects projected into a model eye.

PMID- 24889022
TI  - Identification and estimation of survivor average causal effects.
AB  - In longitudinal studies, outcomes ascertained at follow-up are typically
      undefined for individuals who die prior to the follow-up visit. In such settings,
      outcomes are said to be truncated by death and inference about the effects of a
      point treatment or exposure, restricted to individuals alive at the follow-up
      visit, could be biased even if as in experimental studies, treatment assignment
      were randomized. To account for truncation by death, the survivor average causal
      effect (SACE) defines the effect of treatment on the outcome for the subset of
      individuals who would have survived regardless of exposure status. In this paper,
      the author nonparametrically identifies SACE by leveraging post-exposure
      longitudinal correlates of survival and outcome that may also mediate the
      exposure effects on survival and outcome. Nonparametric identification is
      achieved by supposing that the longitudinal data arise from a certain
      nonparametric structural equations model and by making the monotonicity
      assumption that the effect of exposure on survival agrees in its direction across
      individuals. A novel weighted analysis involving a consistent estimate of the
      survival process is shown to produce consistent estimates of SACE. A data
      illustration is given, and the methods are extended to the context of time
      varying exposures. We discuss a sensitivity analysis framework that relaxes
      assumptions about independent errors in the nonparametric structural equations
      model and may be used to assess the extent to which inference may be altered by a
      violation of key identifying assumptions.

PMID- 24889025
TI  - Synergism and rules of the new combination drug Yiqijiedu formulae (YQJD) on
      ischemic stroke based on amino acids (AAs) metabolism.
AB  - The use of combination drugs is considered to be a promising strategy to control
      complex diseases such as ischemic stroke. The detection of metabolites has been
      used as a versatile tool to reveal the potential mechanism of diverse diseases.
      In this study, the levels of 12 endogenous AAs were simultaneously determined
      quantitatively in the MCAO rat brain using RRLC-QQQ method. Seven AAs were chosen
      as the potential biomarkers, and using PLS-DA analysis, the effects of the new
      combination drug YQJD, which is composed of ginsenosides, berberine, and
      jasminoidin, on those 7 AAs were evaluated. Four AAs, glutamic acid,
      homocysteine, methionine, and tryptophan, which changed significantly in the YQJD
      treated groups compared to the vehicle groups (P < 0.05), were identified and
      designated as the AAs to use to further explore the synergism of YQJD. The result
      of a PCA showed that the combination of these three drugs exhibits the strongest
      synergistic effect compared to other combination groups and that ginsenosides
      might play a pivotal role, especially when combined with jasminoidin. We
      successfully explored the synergetic mechanism of multi-component and provided a
      new method for evaluating the integrated effects of combination drugs in the
      treatment of complex diseases. 

PMID- 24889026
TI  - Binding SNOMED CT terms to archetype elements. Establishing a baseline of
      results.
AB  - INTRODUCTION: This article is part of the Focus Theme of METHODS of Information
      in Medicine on "Managing Interoperability and Complexity in Health Systems".
      BACKGROUND: The proliferation of archetypes as a means to represent information
      of Electronic Health Records has raised the need of binding terminological codes 
      such as SNOMED CT codes - to their elements, in order to identify them
      univocally. However, the large size of the terminologies makes it difficult to
      perform this task manually. OBJECTIVES: To establish a baseline of results for
      the aforementioned problem by using off-the-shelf string comparison-based
      techniques against which results from more complex techniques could be evaluated.
      METHODS: Nine Typed Comparison METHODS were evaluated for binding using a set of
      487 archetype elements. Their recall was calculated and Friedman and Nemenyi
      tests were applied in order to assess whether any of the methods outperformed the
      others. RESULTS: Using the qGrams method along with the 'Text' information piece
      of archetype elements outperforms the other methods if a level of confidence of
      90% is considered. A recall of 25.26% is obtained if just one SNOMED CT term is
      retrieved for each archetype element. This recall rises to 50.51% and 75.56% if
      10 and 100 elements are retrieved respectively, that being a reduction of more
      than 99.99% on the SNOMED CT code set. CONCLUSIONS: The baseline has been
      established following the above-mentioned results. Moreover, it has been observed
      that although string comparison-based methods do not outperform more
      sophisticated techniques, they still can be an alternative for providing a
      reduced set of candidate terms for each archetype element from which the ultimate
      term can be chosen later in the more-than-likely manual supervision task.

PMID- 24889027
TI  - Salvaging an accidental superior vena caval transection during a right
      pneumonectomy by creating a Glenn shunt: a case report and review of the
      literature.

PMID- 24889028
TI  - Hybrid approach for transcatheter paravalvular leak closure of mitral prosthesis
      in high-risk patients through transapical access.
AB  - OBJECTIVES: To report "hybrid" procedure feasibility and the clinical success of
      transcatheter paravalvular leak closure through apical access. METHODS: Seven
      patients (73.6+/-6.1 years; 4 men) with severe mitral prosthesis paravalvular
      leak were selected. All patients were at high risk for open surgery because of
      severe comorbidities and heart failure (New York Heart Association class III-IV).
      RESULTS: The defect size was 25+/-7.8 mm in the long axis and 9.3+/-2 mm in the
      short axis. Two defects were detected in 2 patients. The transapical procedure
      was performed in a "hybrid" surgery room using minithoracotomy and general
      anesthesia. Three-dimensional transesophageal echocardiography and fluoroscopy
      were used for imaging. A total of 19 Amplatzer Vascular Plug III devices (St Jude
      Medical) were implanted in 7 patients, 2.7/patient and 1 to 3/fistula. The
      procedure time was 150.7+/-66.8 minutes. In 6 of 7 patients (85.7%), the
      paravalvular leak was successfully closed, resulting in no or mild residual
      regurgitation. One patient had moderate regurgitation despite deployment of 3
      Amplatzer Vascular Plug III devices. Two patients required blood transfusion
      related to procedural blood loss. The patients were discharged at 15.3+/-6.5 days
      and followed up at 215.7+/-138.6 days. All but 1 patient reported symptomatic
      improvement by >=1 New York Heart Association class at follow-up. One patient
      died 216 days postoperatively. CONCLUSIONS: A "hybrid approach" for transcatheter
      paravalvular leak closure of mitral prosthesis from the apical route is effective
      in reducing the regurgitation grade and improving functional capacity in high
      risk patients. Complete closure of the defect was maintained at follow-up in most
      patients.

PMID- 24889029
TI  - Self-assembly of azide containing dipeptides.
AB  - Functional structures and materials are formed spontaneously in nature through
      the process of self-assembly. Mimicking this process in vitro will lead to the
      formation of new substances that would impact many areas including energy
      production and storage, biomaterials and implants, and drug delivery. The
      considerable structural diversity of peptides makes them appealing building
      blocks for self-assembly in vitro. This paper describes the self-assembly of
      three aromatic dipeptides containing an azide moiety: H-Phe(4-azido)-Phe(4-azido)
      OH, H-Phe(4-azido)-Phe-OH, and H-Phe-Phe(4-azido)-OH. The peptide H-Phe(4-azido)
      Phe(4-azido)-OH self-assembled into porous spherical structures, whereas the
      peptides H-Phe(4-azido)-Phe-OH and H-Phe-Phe(4-azido)-OH did not form any ordered
      structures under the examined experimental conditions. The azido group of the
      peptide can serve as a photo cross-linking agent upon irradiation with UV light.
      To examine the effect of this group and its activity on the self-assembled
      structures, we irradiated the assemblies in solution for different time periods.
      Using electron microscopy, we determined that the porous spherical assemblies
      formed by the peptide H-Phe(4-azido)-Phe(4-azido)-OH underwent a structural
      change upon irradiation. In addition, using FT-IR, we detected the chemical
      change of the peptide azido group. Moreover, using indentation experiments with
      atomic force microscopy, we showed that the Young's modulus of the spherical
      assemblies increased after 20 min of irradiation with UV light. Overall,
      irradiating the solution of the peptide assemblies containing the azido group
      resulted in a change both in the morphology and mechanical properties of the
      peptide-based structures. These ordered assemblies or their peptide monomer
      building blocks can potentially be incorporated into other peptide assemblies to
      generate stiffer and more stable materials.

PMID- 24889030
TI  - Improved standards for prenatal diagnosis of citrullinemia.
AB  - Citrullinemia type I is a urea cycle disorder caused by autosomal recessive
      mutations in argininosuccinate synthetase 1 (ASS1). In the classical form of this
      disease, symptoms manifest during the neonatal period as progressive lethargy,
      poor feeding, and central nervous system depression secondary to hyperammonemia.
      In pregnancies involving two carrier parents, prenatal diagnosis is important for
      both reproductive decisions and advanced preparation for neonatal care. The
      current gold standard for prenatal diagnosis has been the citrulline
      incorporation assay in addition to DNA mutation analysis. Herein, we review our
      experience with prenatal diagnosis of citrullinemia type I over the span of 11
      years in 41 at-risk pregnancies. During this time, we identified 15 affected
      fetuses using a combination of molecular and biochemical testing. Given the
      established limitations of both the citrulline incorporation assay as well DNA
      mutation analysis, we probed our data to assess the value of amniotic fluid amino
      acid levels in prenatal diagnosis. Previous publications have proposed using the
      amniotic fluid ratio of citrulline/(arginine+ornithine) in prenatal diagnosis;
      however, we noted that amniotic fluid arginine levels were normal in our cohort
      and hypothesized that the amniotic fluid citrulline/ornithine ratio may be
      superior. Indeed, our analyses revealed that the ratio of amniotic fluid
      citrulline/ornithine alone correctly distinguished affected from unaffected
      fetuses in all cases. During the establishment of a normal reference range we
      discovered significant elevations in amniotic fluid citrulline levels in at-risk
      pregnancies compared to the normal population even when the fetus was unaffected.
      This highlights the importance of using amniotic fluid from carrier mothers when
      setting up a normal reference range. Finally, we report our experience as one of
      the first centers to adopt Sanger sequencing for prospective prenatal diagnosis
      of citrullinemia. While this is clearly a useful tool in many cases, we
      encountered families for whom molecular analysis uncovered variants of unknown
      clinical significance or no mutation at all. Based upon these new findings, we
      recommend a combinatorial approach involving ASS1 sequencing and amniotic fluid
      citrulline/ornithine for the prenatal diagnosis of citrullinemia type I.

PMID- 24889031
TI  - The Mmachc gene is required for pre-implantation embryogenesis in the mouse.
AB  - Patients with mutations in MMACHC have the autosomal recessive disease of
      cobalamin metabolism known as cblC. These patients are unable to convert
      cobalamin into the two active forms, methylcobalamin and adenosylcobalamin and
      consequently have elevated homocysteine and methylmalonic acid in blood and
      urine. In addition, some cblC patients have structural abnormalities, including
      congenital heart defects. MMACHC is conserved in the mouse and shows tissue and
      stage-specific expression pattern in midgestation stage embryos. To create a
      mouse model of cblC we generated a line of mice with a gene-trap insertion in
      intron 1 of the Mmachc gene, (Mmachc(Gt(AZ0348)Wtsi)). Heterozygous mice show a
      50% reduction of MMACHC protein, and have significantly higher levels of
      homocysteine and methylmalonic acid in their blood. The Mmachc(Gt) allele was
      inherited with a transmission ratio distortion in matings with heterozygous
      animals. Furthermore, homozygous Mmachc(Gt) embryos were not found after
      embryonic day 3.5 and these embryos were unable to generate giant cells in
      outgrowth assays. Our findings confirm that cblC is modeled in mice with reduced
      levels of Mmachc and suggest an early requirement for Mmachc in mouse
      development. 

PMID- 24889032
TI  - The influence of physiological matrix conditions on permanent culture of induced
      pluripotent stem cell-derived cardiomyocytes.
AB  - Cardiomyocytes (CMs) from induced pluripotent stem (iPS) cells mark an important
      achievement in the development of in vitro pharmacological, toxicological and
      developmental assays and in the establishment of protocols for cardiac cell
      replacement therapy. Using CMs generated from murine embryonic stem cells and iPS
      cells we found increased cell-matrix interaction and more matured embryoid body
      (EB) structures in iPS cell-derived EBs. However, neither suspension-culture in
      form of purified cardiac clusters nor adherence-culture on traditional cell
      culture plastic allowed for extended culture of CMs. CMs grown for five weeks on
      polystyrene exhibit signs of massive mechanical stress as indicated by alpha
      smooth muscle actin expression and loss of sarcomere integrity. Hydrogels from
      polyacrylamide allow adapting of the matrix stiffness to that of cardiac tissue.
      We were able to eliminate the bottleneck of low cell adhesion using 2,5
      Dioxopyrrolidin-1-yl-6-acrylamidohexanoate as a crosslinker to immobilize matrix
      proteins on the gels surface. Finally we present an easy method to generate
      polyacrylamide gels with a physiological Young's modulus of 55 kPa and defined
      surface ligand, facilitating the culture of murine and human iPS-CMs, removing
      excess mechanical stresses and reducing the risk of tissue culture artifacts
      exerted by stiff substrates. 

PMID- 24889033
TI  - Adamantane-based dendrons for trimerization of the therapeutic P140 peptide.
AB  - Dendrons constituted of an adamantane core, a focal point and three arms, were
      synthetized starting from a multifunctional adamantane derivative. Maleimido
      groups at the periphery of the scaffold were used to covalently attach the
      peptide called P140, a therapeutic phosphopeptide controlling disease activity in
      systemic lupus, both in mice and patients. Biotinylation of the trimers at the
      focal point was performed using click chemistry and the conjugates were studied
      in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70
      chaperone protein, effect on HSPA8 folding property and in vivo activity. The
      results showed that the trimerization of P140 peptide does not trigger
      aggregation or steric hindrances during the interaction with HSPA8 protein.
      Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed
      the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in
      MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control
      trimer synthesized with the same scaffold and a scrambled sequence of P140 showed
      no effect in vivo. This work reveals that adamantane-based scaffolds with a well
      defined spatial conformation are promising trivalent systems for molecular
      recognition and for biomedical applications. 

PMID- 24889034
TI  - Variations in mitochondrial membrane potential correlate with malic acid
      production by natural isolates of Saccharomyces cerevisiae sake strains.
AB  - Research on the relationship between mitochondrial membrane potential and
      fermentation profile is being intensely pursued because of the potential for
      developing advanced fermentation technologies. In the present study, we isolated
      naturally occurring strains of yeast from sake mash that produce high levels of
      malic acid and demonstrate that variations in mitochondrial membrane potential
      correlate with malic acid production. To define the underlying biochemical
      mechanism, we determined the activities of enzymes required for malic acid
      synthesis and found that pyruvate carboxylase and malate dehydrogenase activities
      in strains that produce high levels of malic acid were elevated compared with the
      standard sake strain K901. These results inspired us to hypothesize that
      decreased mitochondrial membrane potential was responsible for increased malic
      acid synthesis, and we present data supporting this hypothesis. Thus, the
      mitochondrial membrane potential of high malic acid producers was lower compared
      with standard strains. We conclude that mitochondrial membrane potential
      correlates with malic acid production. 

PMID- 24889035
TI  - Arthropod-borne pathogens circulating in free-roaming domestic cats in a zoo
      environment in Brazil.
AB  - Recently, tick and flea-borne pathogens have been detected in wild carnivores
      maintained in captivity in Brazilian zoos. Since free-roaming cats are frequently
      found in Brazilian zoos, they could act as reservoirs for arthropod-borne
      pathogens, which could be transmitted to endangered wild carnivores maintained in
      captivity in these institutions. On the other hand, stray cats in zoos may play a
      role as sentinels to pathogens that circulate among wild animals in captivity.
      The present work aimed to detect the presence of Anaplasmataceae agents,
      hemoplasmas, Bartonella species, piroplasmas, and Hepatozoon sp. DNA in blood
      samples of 37 free-roaming cats in a Brazilian zoo. Three (8%) cats were positive
      for Anaplasma spp. closed related to Anaplasma phagocytophilum; 12 (32%) cats
      were positive for hemoplasmas [two (5%) for Mycoplasma haemofelis, five (13.5%)
      for Candidatus Mycoplasma haemominutum, and five (13.5%) for Candidatus
      Mycoplasma turicensis]; 11 (30%) were positive for Bartonella spp., six (16%)
      were positive Babesia vogeli and one (3%) for Theileria sp. Coinfection with
      multiple arthropod-borne agentes was observed in sampled cats. None of sampled
      cats were positive for Ehrlichia spp., Cytauxzoon spp., or Hepatozoon spp. in
      PCR. This is the first molecular detection of Babesia vogeli and Theileria sp. in
      domestic cats in Brazil. The control of the population of free-roaming cats in
      these conservation institutions is much needed aiming to prevent the potential
      transmission to endangered wild animals maintained in captivity, such as wild
      neotropical wild felids, as well as to human beings visiting zoos. 

PMID- 24889036
TI  - Seroprevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis
      virus in zoo animal species in the Czech Republic.
AB  - This study was conducted to evaluate the prevalence of antibodies against
      Borrelia bugdorferi (Bb) s.l. and tick-borne encephalitis virus (TBEV) in zoo
      animals in the Czech Republic. We collected 133 serum samples from 69 animal
      species from 5 zoos located in different parts of the country. The samples were
      obtained from even-toed ungulates (n=78; 42 species), odd-toed ungulates (n=32;
      11 species), carnivores (n=13; 9 species), primates (n=2, 2 species), birds (n=3;
      2 species), and reptiles (n=5; 3 species). A high antibody prevalence (60%) was
      observed for Bb s.l. On the other hand, only two animals had TBEV-specific
      antibodies: a markhor (Capra falconeri) and a reindeer (Rangifer tarandus), both
      from the same zoo, located in an area endemic for TBEV. Both of these animals
      were also positive for Bb s.l. antibodies. Our results indicate that a high
      number of animal species in the Czech zoos were exposed to Bb s.l. and that TBEV
      infection occurred at least in one of the investigated zoos. Considering the
      pathogenic potential of these two tick-borne pathogens, clinical and serological
      monitoring should be continued, and therapeutic and preventive measures should be
      taken when necessary. 

PMID- 24889040
TI  - Impaired glycemia and Alzheimer's disease.

PMID- 24889041
TI  - PERK mediates eIF2alpha phosphorylation responsible for BACE1 elevation, CREB
      dysfunction and neurodegeneration in a mouse model of Alzheimer's disease.
AB  - Emerging evidence suggests that aberrant phosphorylation of eukaryotic initiation
      factor-2alpha (eIF2alpha) may induce synaptic failure and neurodegeneration
      through persistent translational inhibition of global protein synthesis. However,
      elevated phospho-eIF2alpha also paradoxically causes translational activation of
      a subset of messenger RNAs such as the beta-secretase enzyme, beta-site APP
      cleaving enzyme 1 (BACE1) and cAMP response element binding protein (CREB)
      repressor, activating transcription factor 4 (ATF4). Therefore, we tested whether
      genetic reduction of the eIF2alpha kinase PERK may prevent these deleterious
      events and mitigate Alzheimer's disease (AD)-like neuropathology and cognitive
      impairments in the 5XFAD mouse model. PERK haploinsufficiency blocked
      overactivation of the PERK-eIF2alpha pathway, as evidenced by significant
      reductions in phosphorylation of PERK and eIF2alpha, in 5XFAD mice. PERK
      haploinsufficiency was sufficient to rescue memory deficits and cholinergic
      neurodegeneration in this AD model. Notably, PERK haploinsufficiency also
      prevented BACE1 elevations, resulting in reduced levels of amyloid-beta peptides
      and plaque burden in 5XFAD mice. Moreover, CREB dysfunction was restored in
      PERK(+/-).5XFAD mice concomitant with reversal of ATF4 upregulation. Together,
      these findings suggest that PERK may be a disease-modifying therapeutic target to
      prevent multiple memory-disrupting mechanisms associated with AD. 

PMID- 24889045
TI  - Laboring on fetal monitoring.

PMID- 24889044
TI  - Seminal plasma proteome of electroejaculated Bos indicus bulls.
AB  - The present study describes the seminal plasma proteome of Bos indicus bulls.
      Fifty-six, 24-month old Australian Brahman sires were evaluated and subjected to
      electroejaculation. Seminal plasma proteins were separated by 2-D SDS-PAGE and
      identified by mass spectrometry. The percentage of progressively motile and
      morphologically normal sperm of the bulls were 70.4 +/- 2.3 and 64 +/- 3.2%,
      respectively. A total of 108 spots were identified in the 2-D maps, corresponding
      to 46 proteins. Binder of sperm proteins accounted for 55.8% of all spots
      detected in the maps and spermadhesins comprised the second most abundant
      constituents. Other proteins of the Bos indicus seminal plasma include clusterin,
      albumin, transferrin, metalloproteinase inhibitor 2, osteopontin, epididymal
      secretory protein E1, apolipoprotein A-1, heat shock 70 kDa protein, glutathione
      peroxidase 3, cathelicidins, alpha-enolase, tripeptidyl-peptidase 1, zinc-alpha-2
      glycoprotein, plasma serine protease inhibitor, beta 2-microglobulin, proteasome
      subunit beta type-4, actin, cathepsins, nucleobinding-1, protein S100-A9,
      hemoglobin subunit alpha, cadherin-1, angiogenin-1, fibrinogen alpha and beta
      chain, ephirin-A1, protein DJ-1, serpin A3-7, alpha-2-macroglobulin, annexin A1,
      complement factor B, polymeric immunoglobulin receptor, seminal ribonuclease,
      ribonuclease-4, prostaglandin-H2 d-isomerase, platelet-activating factor
      acetylhydrolase, and phosphoglycerate kinase 1. In conclusion, this work uniquely
      portrays the Bos indicus seminal fluid proteome, based on samples from a large
      set of animals representing the Brahman cattle of the tropical Northern
      Australia. Based on putative biochemical attributes, seminal proteins act during
      sperm maturation, protection, capacitation and fertilization.

PMID- 24889046
TI  - CTG or STAN--with or without FBS?

PMID- 24889042
TI  - Comparison of HER2 status between surgically resected specimens and matched
      biopsy specimens of gastric intestinal-type adenocarcinoma.
AB  - HER2 protein overexpression and gene amplification are important biomarkers for
      identifying gastric cancer patients who may respond to HER2-targeted therapy
      using trastuzumab. The aim of this study was to evaluate the concordance between
      HER2 protein expression and gene amplification in both surgically resected tumors
      and matched biopsy specimens of gastric cancer. Formalin-fixed, paraffin-embedded
      sections of 207 surgically resected tumors and 158 biopsy specimens from 207
      cases of invasive intestinal-type gastric cancer were analyzed. Protein
      expression was assessed using immunohistochemistry and graded by the modified
      scoring criteria for gastric cancer. Gene amplification was evaluated by
      fluorescence in situ hybridization (FISH). HER2 overexpression was observed in 17
      % of both surgically resected tumors (35/207) and biopsy specimens (26/158). HER2
      gene amplification was detected in 31 % (61/200) of surgically resected tumors
      and 32 % (47/147) of biopsy specimens. Except for immunohistochemistry (IHC)
      equivocal (2+) cases, the concordance rates between IHC and FISH was 90.9 % in
      surgically resected tumors and 90.2 % in biopsy specimens. In IHC 2+ cases, the
      rate of HER2 gene amplification was 56 and 38 % in surgically resected tumors and
      biopsy specimens, respectively. IHC-FISH discordance was mainly due to
      intratumoral heterogeneity and low-level gene amplification. The concordance rate
      of IHC results between surgically resected specimens and the corresponding biopsy
      specimen was 57.0 % (kappa = 0.224), and in discordant cases, HER2 positivity in
      biopsies and HER2 negativity in surgically resected tumors were most common. The
      concordance rate of FISH results between surgically resected tumors and biopsy
      specimens was 72.7 % (kappa = 0.313). Polysomy 17 was detected in 5.5 and 7.5 %
      of surgically resected tumors and biopsy specimens and significantly correlated
      with IHC score, but polysomy 17 could explain one IHC score 3+ and FISH-negative
      tumor only. Although high concordance rates between HER2-protein expression and
      gene amplification were observed in both surgically resected tumors and biopsy
      specimens, the agreement levels were evaluated to be fair. Polysomy 17 was
      infrequent and seemed to have limited impact on gastric HER2 testing. Further
      investigations are required for an appropriate biopsy method to reduce false
      results of HER2 testing and to clarify the clinical significance of intratumoral
      heterogeneity in HER2 status.

PMID- 24889043
TI  - Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian
      carcinoma.
AB  - Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer
      with characteristic biological features and aggressive clinical behavior. OCCCs
      show a pattern of gene mutations different from other type I ovarian
      malignancies, notably a higher frequency of PIK3CA mutations. In low grade serous
      ovarian cancer, KRAS and BRAF mutations are frequent, but little data are
      available on the mutational status of these genes in OCCCs. To clarify this
      issue, we designed a clinicopathological study with the aim to establish the
      incidence of KRAS, NRAS, and BRAF hot spot mutations in OCCC. Between December
      2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to
      our Institutions. In all cases, final diagnosis was established according to FIGO
      and WHO criteria. All women received complete surgical staging. The PyroMark Q24
      system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of
      KRAS, NRAS, and BRAF hot spot regions on 2.5-MUm sections of formalin-fixed
      paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of KRAS,
      NRAS, and BRAF hot spot regions revealed the presence of mutations only at codon
      12 in exon 2 of KRAS in 3 of 22 (14 %) cases. We found no mutations in the hot
      spot regions of NRAF (exons 2, 3, 4) or BRAF (exon 15). The median age of women
      with a KRAS mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA
      lesions in two cases associated with foci of endometriosis. We conclude that in
      14 % of OCCCs, a KRAS mutation occurs in codon 2 exon 2. NRAS and BRAF mutations
      were not found.

PMID- 24889049
TI  - Enhanced self-assembly of metal oxides and metal-organic frameworks from
      precursors with magnetohydrodynamically induced long-lived collective spin
      states.
AB  - Magneto-hydrodynamic generation of long-lived collective spin states and their
      impact on crystal morphology is demonstrated for three different, technologically
      relevant materials: COK-16 metal organic framework, manganese oxide nanotubes,
      and vanadium oxide nano-scrolls. 

PMID- 24889050
TI  - [Tuberculosis of the gallbladder vs metastatic vesicular carcinoma; a diagnostic
      dilemma].

PMID- 24889051
TI  - "Stent in stent" technique for oesophageal benign hyperplasia. Complications and
      treatment of fistulas after sleeve gastrectomy.

PMID- 24889052
TI  - Distinguishing tropical sprue from celiac disease in returning travellers with
      chronic diarrhoea: a diagnostic challenge?
AB  - BACKGROUND: Within the present era of worldwide travel, it is important for all
      clinicians to consider the possibility of tropical sprue (TS) in returning
      patients with persistent diarrhoea after travel. The symptoms and histologic
      findings of TS can resemble but also be confused with celiac disease (CD).
      MATERIAL AND METHOD: Patients at our institute diagnosed with CD or TS in the
      period January 2000-December 2010 were eligible for inclusion. Of all patients,
      demographic, clinical, laboratory and endoscopy data on admission and in follow
      up were collected retrospectively. RESULTS: 28 CD and 7 TS patients were
      included. There were no differences in baseline clinical characteristics,
      duration of stay in a tropical region or in laboratory findings on admission.
      However, in the majority of CD patients antibodies against endomysium (EMA) or
      tissue transglutaminase (tTG) were present at presentation but absent in all TS
      patients at presentation. CONCLUSIONS: In returning travellers with persistent
      diarrhoea, a diagnosis of CD is unlikely in case of absence of anti-EMA or anti
      tTG antibodies but conversely increases the likelihood of TS. This distinct
      immunoserological profile may be of help in selecting the optimal treatment in
      returning travelers with chronic diarrhoea after staying in a tropical region.

PMID- 24889053
TI  - Younger age, recent HIV diagnosis, no welfare support and no annual sexually
      transmissible infection screening are associated with nonuse of antiretroviral
      therapy among HIV-positive gay men in Australia.
AB  - OBJECTIVES: With the increasing momentum to maximize the benefits of
      antiretroviral therapy (ART), better understanding of opportunities and
      challenges in increasing ART coverage and promoting early ART initiation is
      urgently needed. Key sociodemographic, clinical and behavioural factors
      associated with Australian HIV-positive gay men's current nonuse of ART were
      systematically examined. METHODS: Data were based on 1911 responses from HIV
      positive men who had participated in the Australian Gay Community Periodic
      Surveys (GCPS) between 2010 and 2012. Stratified univariate analysis and
      multivariate logistic regression were used. RESULTS: A majority of the
      participants were recruited from gay community venues and events and self
      identified as gay or homosexual. On average, they were 44 years old and had been
      living with HIV for at least 10 years. Close to 80% (n=1555) were taking ART,
      with >90% further reporting an undetectable viral load at the time of the survey.
      From 2010 to 2012, there had been a moderate increase in ART uptake [adjusted
      odds ratio (AOR) 1.40; 95% confidence interval (CI) 1.20-1.65]. In addition,
      younger age (AOR 1.66; 95% CI 1.45-1.92), recent HIV diagnosis (AOR 1.78; 95% CI
      1.59-1.98), not receiving any social welfare payments (AOR 2.20; 95% CI 1.05
      2.54) and no annual screening for sexually transmissible infections (AOR 1.55;
      95% CI 1.03-2.34) were independently associated with ART nonuse. CONCLUSIONS:
      Current ART coverage among HIV-positive gay men in Australia is reasonably high.
      To further increase ART coverage and promote early ART initiation in this
      population, better clinical care and sustained structural support are needed for
      HIV management throughout their life course.

PMID- 24889054
TI  - Family employment and child socioemotional behaviour: longitudinal findings from
      the UK Millennium Cohort Study.
AB  - BACKGROUND: Levels of paid employment in two parent and lone parent families have
      increased in the UK but evidence of its impact on child socioemotional behaviour
      is limited and inconsistent. METHODS: We conducted a longitudinal analysis using
      the first four sweeps of the Millennium Cohort Study (9 months, 3 years, 5 years
      and 7 years) to investigate the influence of family employment trajectories in
      the early years on socioemotional behaviour at 7 years, unadjusted and adjusted
      for covariates. In addition, mothers' employment was investigated separately.
      RESULTS: Children from families where no parent was employed for one or more
      sweeps were at a greater risk of socioemotional problem behaviour compared with
      those where a parent was continuously employed, even after adjustment for
      covariates. Children of mothers who were non-employed for one or more sweeps were
      at greater risk of problem behaviour compared with mothers who were employed at
      all sweeps. Adjustment for covariates fully attenuated the excess risk for
      children whose mothers had moved into employment by the time they were 7 years.
      In contrast, the elevated risk associated with continuous non-employment and a
      single transition out of employment was attenuated after adjustment for early
      covariates, fathers' employment, household income and mothers' psychological
      distress at 7 years, but remained significant. CONCLUSIONS: Family and mothers'
      employment were associated with a lower risk of problem behaviour for children in
      middle childhood, in part explained by sociodemographic characteristics of
      families and the apparent psychological and socioeconomic benefits of employment.
      Results for mothers' transitions in or out of the labour market suggest that
      child problem behaviour is influenced by current status, over and above diverse
      earlier experiences of employment and non-employment.

PMID- 24889055
TI  - Role of the penetration-resistance genes PEN1, PEN2 and PEN3 in the
      hypersensitive response and race-specific resistance in Arabidopsis thaliana.
AB  - Plants are highly capable of recognizing and defending themselves against
      invading microbes. Adapted plant pathogens secrete effector molecules to suppress
      the host's immune system. These molecules may be recognized by host-encoded
      resistance proteins, which then trigger defense in the form of the hypersensitive
      response (HR) leading to programmed cell death of the host tissue at the
      infection site. The three proteins PEN1, PEN2 and PEN3 have been found to act as
      central components in cell wall-based defense against the non-adapted powdery
      mildew Blumeria graminis fsp. hordei (Bgh). We found that loss of function
      mutations in any of the three PEN genes cause decreased hypersensitive cell death
      triggered by recognition of effectors from oomycete and bacterial pathogens in
      Arabidopsis. There were considerable additive effects of the mutations. The HR
      induced by recognition of AvrRpm1 was almost completely abolished in the pen2
      pen3 and pen1 pen3 double mutants and the loss of cell death could be linked to
      indole glucosinolate breakdown products. However, the loss of the HR in pen
      double mutants did not affect the plants' ability to restrict bacterial growth,
      whereas resistance to avirulent isolates of the oomycete Hyaloperonospora
      arabidopsidis was strongly compromised. In contrast, the double and triple
      mutants demonstrated varying degrees of run-away cell death in response to Bgh.
      Taken together, our results indicate that the three genes PEN1, PEN2 and PEN3
      extend in functionality beyond their previously recognized functions in cell wall
      based defense against non-host pathogens.

PMID- 24889056
TI  - Levels and variability of metals in soils of the province of Golestan (Iran).
AB  - Studying the concentration distribution of metals is necessary for soil pollution
      monitoring and maintaining environmental quality. To date, very little large
      scale research has been performed to investigate metal contamination in
      developing countries. In this study, the content and spatial distributions of
      five metals (cadmium [Cd], copper [Cu], nickel [Ni], lead [Pb], and zinc [Zn])
      were quantified based on 346 topsoil samples from 12 districts in the province of
      Golestan (northeast [NE] Iran). The concentration levels (mg/kg) of Cd, Cu, Pb,
      Ni and Zn varied from 0.02 to 0.36, 9.3 to 93.7, 6.8 to 44, 9.5 to 85.35, and 25
      to 417.4, respectively. The average concentrations (mg/kg) obtained were as
      follows: Cd 0.12 +/- 0.07, Cu 23.9 +/- 9.07, Ni 34.88 +/- 11.59, Pb 15.42 +/-
      5.81 and Zn 82.08 +/- 30.87. Significant differences in the distribution of trace
      elements among districts were detected. The AzadShahr and BandarGaz districts
      displayed the highest metal concentrations. Greater metal values were obtained in
      the central, south, west, and NE areas, although Zn concentration was also high
      to the north of the province. Values of contamination factor and contamination
      degree indicated that the metal pollution level was on the order of Zn > Cd > Pb
      > Cu > Ni and that all of the metals belonged to a low or moderate pollution
      category. Ni and Cu levels derived from natural sources, whereas Cd, Pb, and Zn
      derived from anthropogenic activities with greater mean concentrations than
      reference concentrations.

PMID- 24889057
TI  - Development and maintenance of a biospecimen repository for clinical samples
      derived from pulmonary patients.
AB  - The Pulmonary Biospecimen Repository (PBR) at the University of Alabama at
      Birmingham (UAB) was launched in 2009. The purpose of the UAB PBR is to provide
      investigators within the pulmonary community at UAB and elsewhere with clinical
      samples derived from multiple lung diseases, including transplant recipients,
      idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic
      fibrosis, and asthma. Cell and fluid samples isolated from bronchoalveolar lavage
      (BAL), plasma, and serum are collected and stored; samples are assessed routinely
      for viability. Each sample is linked directly with the respective patient
      information via the Pulmonary Translational Research and Clinical Database, a
      Health Insurance Portability and Accountability Act compliant database that
      includes detailed information allowing for the study of specific patient cohorts.
      To access samples, investigators must complete a request form, which is reviewed
      by the UAB PBR Steering Committee. To date, more than 800 patients have provided
      approximately 7,000 BAL, serum and plasma fluid, and cell samples. Over the past
      4 years, nearly 800 of these samples have been distributed to investigators at
      UAB and elsewhere. Future plans for the UAB PBR include expanding sample
      collection to additional pulmonary diseases, such as mycobacterial infections,
      increasing the number of sample users and obtaining external funding to ensure
      its continued sustainability. 

PMID- 24889058
TI  - Invited review--Applications for 3D printers in veterinary medicine.
AB  - Recent technological advances in 3D printing have resulted in increased use of
      this technology in human medicine, and decreasing cost is making it more
      affordable for veterinary use. Rapid prototyping is at its early stage in
      veterinary medicine but clinical, educational, and experimental possibilities
      exist. Techniques and applications, both current and future, are explored and
      illustrated in this article. 

PMID- 24889061
TI  - Sun protection and hydration of stratum corneum: a study by 2-D differential
      method.
AB  - OBJECTIVE: The stratum corneum is the outermost layer of the skin. Its components
      and its morphology (such as the size of its cells) play a role in sun protection,
      and it has been noted that the stratum corneum hydration can change these
      properties. Sunscreens, applied on the skin, can be more or less effective
      depending on the stratum corneum characteristics. We therefore propose to
      simulate the quality of the sun protection and the effect of the stratum corneum
      hydration on the sun protection. METHODS: We first determined the sunscreen
      distribution on a plastic substrate using an optical coherence tomography device.
      We were then able to calculate, by 2-D differential method, the extinction of
      several sunscreens. We modelled the hydration of the stratum corneum, by changing
      the substrate with corneocytes of different thicknesses. RESULTS: Our results
      showed that hydrated stratum corneum protects more against the UV. The benefit
      from changing the substrate varies depending on the sunscreen applied.
      CONCLUSION: We modelled sunscreens on different substrates using electromagnetic
      simulations. To compare these results with measurements, we have to carefully
      hydrate or dehydrate the SC: the simulations did not take into account
      modifications of the surface (water on the surface for example) or any change in
      the characteristics of the stratum corneum other than the modification of the
      corneocytes thickness.

PMID- 24889059
TI  - Tandem mass spectral libraries of peptides in digests of individual proteins:
      Human Serum Albumin (HSA).
AB  - This work presents a method for creating a mass spectral library containing
      tandem spectra of identifiable peptide ions in the tryptic digestion of a single
      protein. Human serum albumin (HSA(1)) was selected for this purpose owing to its
      ubiquity, high level of characterization and availability of digest data. The
      underlying experimental data consisted of ~3000 one-dimensional LC-ESI-MS/MS runs
      with ion-trap fragmentation. In order to generate a wide range of peptides,
      studies covered a broad set of instrument and digestion conditions using multiple
      sources of HSA and trypsin. Computer methods were developed to enable the
      reliable identification and reference spectrum extraction of all peptide ions
      identifiable by current sequence search methods. This process made use of both
      MS2 (tandem) spectra and MS1 (electrospray) data. Identified spectra were
      generated for 2918 different peptide ions, using a variety of manually-validated
      filters to ensure spectrum quality and identification reliability. The resulting
      library was composed of 10% conventional tryptic and 29% semitryptic peptide
      ions, along with 42% tryptic peptide ions with known or unknown modifications,
      which included both analytical artifacts and post-translational modifications
      (PTMs) present in the original HSA. The remaining 19% contained unexpected missed
      cleavages or were under/over alkylated. The methods described can be extended to
      create equivalent spectral libraries for any target protein. Such libraries have
      a number of applications in addition to their known advantages of speed and
      sensitivity, including the ready re-identification of known PTMs, rejection of
      artifact spectra and a means of assessing sample and digestion quality. 

PMID- 24889060
TI  - Measuring fate and rate of single-molecule competition of amplification and
      restriction digestion, and its use for rapid genotyping tested with hepatitis C
      viral RNA.
AB  - We experimentally monitored, at the single-molecule level, the competition among
      reverse transcription, exponential amplification (RT-LAMP), and linear
      degradation (restriction enzymes) starting with hepatitis C viral RNA molecules.
      We found significant heterogeneity in the rate of single-molecule amplification;
      introduction of the restriction enzymes affected both the rate and the "fate"
      (the binary outcome) of single-molecule amplification. While end-point digital
      measurements were primarily sensitive to changes in fate, the bulk real-time
      kinetic measurements were dominated by the rate of amplification of the earliest
      molecules, and were not sensitive to fate of the rest of the molecules. We show
      how this competition of reactions can be used for rapid HCV genotyping with
      either digital or bulk readout. This work advances our understanding of single
      molecule dynamics in reaction networks and may help bring genotyping capabilities
      out of clinical labs and into limited-resource settings. 

PMID- 24889062
TI  - Auto-induction of phase I and phase II metabolism of artemisinin in healthy
      Chinese subjects after oral administration of a new artemisinin-piperaquine fixed
      combination.
AB  - BACKGROUND: Artequick is a relatively inexpensive artemisinin (Qing-hao-su; QHS)
      based combination therapy (ACT) that contains QHS and piperaquine (PQ), which has
      not been widely used because of the decreased concentration level of QHS after
      repeated oral administrations for five to seven days as a monotherapy. This study
      was designed to evaluate the potential auto-induction metabolism of QHS in
      healthy Chinese adults after a two-day oral administration of QHS-PQ. The effect
      of QHS-PQ on the activity of the CYP2B6 and CYP3A4 was also investigated.
      METHODS: Fourteen healthy Chinese subjects received two-day oral doses of QHS-PQ
      (Artequick). A two-drug cocktail consisting of bupropion and midazolam was used
      to assess the activities of CYP2B6 and CYP3A, respectively. Plasma samples were
      analysed for QHS and its phase I/II metabolites, probe drugs and their
      metabolites, using a validated liquid chromatography tandem mass spectrometric
      (LC-MS) method. RESULTS: Four major phase I metabolites of QHS (M1-M3 and deoxy
      QHS) and two subsequent phase II metabolites (M4-M5) were detected in human
      plasma after oral administrations of QHS-PQ. The AUC0-t of the QHS and its phase
      I metabolites decreased significantly (P < 0.05) with increased oral clearance
      (CL/F) after two-day oral doses of QHS-PQ, whereas its phase II metabolites
      exhibited higher AUC (P < 0.01). The phase I metabolic capability, calculated by
      the AUC0-t ratio of all phase I metabolites to QHS, increased 1.5-fold after the
      repeated dose (P < 0.01), and the phase II metabolic capability increased 1.5
      fold for M4 and 3.0-fold for M5. The enzyme activity of CYP2B6 and CYP3A4
      increased 2.1-fold and 3.2-fold, respectively, after two-day oral doses of QHS
      PQ. CONCLUSIONS: The auto-induction of both phase I and phase II metabolism of
      QHS was present in healthy Chinese subjects after a recommended two-day oral dose
      of QHS-PQ. The auto-induction metabolism also existed for phase I metabolites of
      QHS. The enzyme activity of CYP2B6 and CYP3A4 was induced after the two-day oral
      doses of QHS-PQ. Based on these results, the alternative common three-day regimen
      for QHS-PQ could probably lead to lower bioavailability of QHS and higher
      potential of drug-drug interaction caused by the induction of drug-metabolizing
      enzymes.

PMID- 24889063
TI  - From metal-organic framework to intrinsically fluorescent carbon nanodots.
AB  - Highly photoluminescent carbon nanodots (CNDs) were synthesized for the first
      time from metal-organic framework (MOF, ZIF-8) nanoparticles. Coupled with
      fluorescence and non-toxic characteristics, these carbon nanodots could
      potentially be used in biosafe color patterning. 

PMID- 24889064
TI  - An investigation of risk factors associated with tooth surface loss: a pilot
      study.
AB  - Few prospective studies have investigated risk factors associated with severe
      tooth surface loss. This case-control study assessed the possible association
      between medical history, diet, psychological profile and salivary pH and flow
      [Delongis 1982, Johansson 1993] with the incidence of severe tooth surface loss.
      A total of 80 subjects (40 cases and 40 age- and gender-matched controls) aged 25
      85 years were recruited. Cases were subjects with severe tooth surface loss, and
      controls with mild tooth surface loss. Conditional logistic regression analysis
      estimated the odds of severe tooth surface loss to be 15.4 times higher for those
      with cardiovascular disease and 16 times for gastrointestinal disturbances. Most
      domains of the psychological profile were associated with elevated risk of severe
      tooth surface loss, particularly the effects of finance and health. Recreational
      drug use and prescription medications were also associated with severe tooth
      surface loss. There was no association between salivary flow and severe tooth
      surface loss. Although not statistically significant, the pH was slightly lower
      in the severe tooth surface loss group.

PMID- 24889066
TI  - Of London buses and the treatment of cytomegalovirus infection.

PMID- 24889065
TI  - Progressive loss of myogenic differentiation in leiomyosarcoma has prognostic
      value.
AB  - AIMS: Well-differentiated leiomyosarcomas show morphologically recognizable
      smooth muscle differentiation, whereas poorly differentiated tumours may form a
      spectrum with a subset of undifferentiated pleomorphic sarcomas. The expression
      of certain muscle markers has been reported to have prognostic impact. We
      investigated the correlation between the morphological spectrum and the muscle
      marker expression profile of leiomyosarcoma, and the impact of these factors on
      patient outcomes. METHODS AND RESULTS: Tissue microarrays including 202 non
      uterine and 181 uterine leiomyosarcomas with a spectrum of tumour morphologies
      were evaluated for expression of immunohistochemical markers of muscle
      differentiation. Poorly differentiated tumours frequently lost one or more
      conventional smooth muscle markers [smooth muscle actin, desmin, h-caldesmon, and
      smooth muscle myosin (P < 0.0001)], as well as the more recently described
      markers SLMAP, MYLK, and ACTG2 (P < 0.0001). In primary tumours, both desmin and
      CFL2 expression predicted improved overall survival in multivariate analyses (P =
      0.0111 and P = 0.043, respectively). Patients with muscle marker-enriched tumours
      (expressing all four conventional markers or any three of ACTG2, CFL2, CASQ2,
      MYLK, and SLMAP) had improved overall survival (P < 0.05) in univariate analyses.
      CONCLUSIONS: Morphologically and immunohistochemically, poorly differentiated
      leiomyosarcomas can masquerade as undifferentiated pleomorphic sarcomas with
      progressive loss of muscle markers. The expression of muscle markers has
      prognostic significance in primary leiomyosarcomas independently of tumour
      morphology.

PMID- 24889067
TI  - Gene expression plasticity evolves in response to colonization of freshwater
      lakes in threespine stickleback.
AB  - Phenotypic plasticity is predicted to facilitate individual survival and/or
      evolve in response to novel environments. Plasticity that facilitates survival
      should both permit colonization and act as a buffer against further evolution,
      with contemporary and derived forms predicted to be similarly plastic for a suite
      of traits. On the other hand, given the importance of plasticity in maintaining
      internal homeostasis, derived populations that encounter greater environmental
      heterogeneity should evolve greater plasticity. We tested the evolutionary
      significance of phenotypic plasticity in coastal British Columbian postglacial
      populations of threespine stickleback (Gasterosteus aculeatus) that evolved under
      greater seasonal extremes in temperature after invading freshwater lakes from the
      sea. Two ancestral (contemporary marine) and two derived (contemporary
      freshwater) populations of stickleback were raised near their thermal tolerance
      extremes, 7 and 22  degrees C. Gene expression plasticity was estimated for more
      than 14,000 genes. Over five thousand genes were similarly plastic in marine and
      freshwater stickleback, but freshwater populations exhibited significantly more
      genes with plastic expression than marine populations. Furthermore, several of
      the loci shown to exhibit gene expression plasticity have been previously
      implicated in the adaptive evolution of freshwater populations, including a gene
      involved in mitochondrial regulation (PPARAa). Collectively, these data provide
      molecular evidence that highlights the importance of plasticity in colonization
      and adaptation to new environments.

PMID- 24889068
TI  - Orbital effect-induced anomalous anion-pi interactions between electron-rich
      aromatic hydrocarbons and fluoride.
AB  - Anion-pi interactions generally exist between an anion and an electron-deficient
      pi-ring because of the electron-accepting character of the ring. In this paper,
      we report orbital effect-induced anomalous binding between electron-rich pi
      systems and F(-) through anion-pi interactions calculated at the MP2/6-31+G(d,p)
      and omegaB97X-D/6-31+G(d,p) levels of theory. We find that anion-pi interactions
      between F(-) and electron-rich pi rings increase markedly with increasing number
      of pi electrons and size of the pi rings. This is contrary to intuition because
      anion-pi interactions would be expected to gradually decrease because of
      gradually increasing Coulombic repulsion between the negative charge of the
      anions and gradually increasing number of pi electrons of the aromatic surfaces.
      Energy decomposition analysis showed that the key to this anomalous effect is the
      more effective delocalization of negative charge to the unoccupied pi* orbitals
      of larger pi rings, which is termed an "orbital effect". 

PMID- 24889069
TI  - Quantitative analysis of surface electromyography during epileptic and
      nonepileptic convulsive seizures.
AB  - OBJECTIVE: To investigate the characteristics of sustained muscle activation
      during convulsive epileptic and psychogenic nonepileptic seizures (PNES), as
      compared to voluntary muscle activation. The main goal was to find surface
      electromyography (EMG) features that can distinguish between convulsive epileptic
      seizures and convulsive PNES. METHODS: In this case-control study, surface EMG
      was recorded from the deltoid muscles during long-term video
      electroencephalography (EEG) monitoring in 25 patients and in 21 healthy
      controls. A total of 46 clinical episodes were recorded: 28 generalized tonic
      clonic seizures (GTCS) from 14 patients with epilepsy, and 18 convulsive PNES
      from 12 patients (one patient had both GTCS and PNES). The healthy controls were
      simulating GTCS. To quantitatively characterize the signals we calculated the
      following parameters: root mean square (RMS) of the amplitude, median frequency
      (MF), coherence, and duration of the seizures, of the clonic EMG discharges, and
      of the silent periods between the cloni. Based on wavelet analysis, we
      distinguished between a low-frequency component (LF 2-8 Hz) and a high-frequency
      component (HF 64-256 Hz). RESULTS: Duration of the seizure, and separation
      between the tonic and the clonic phases distinguished at group-level but not at
      individual level between convulsive PNES and GTCS. RMS, temporal dynamics of the
      HF/LF ratio, and the evolution of the silent periods differentiated between
      epileptic and nonepileptic convulsive seizures at the individual level. A
      combination between HF/LF ratio and RMS separated all PNES from the GTCS. A
      blinded review of the EMG features distinguished correctly between GTCS and
      convulsive PNES in all cases. The HF/LF ratio and the RMS of the PNES were
      smaller compared to the simulated seizures. SIGNIFICANCE: In addition to
      providing insight into the mechanism of muscle activation during convulsive PNES,
      these results have diagnostic significance, at the individual level. Surface EMG
      features can accurately distinguish convulsive epileptic from nonepileptic
      psychogenic seizures, even in PNES cases without rhythmic clonic movements.

PMID- 24889070
TI  - Preparing a cell for nuclear envelope breakdown: Spatio-temporal control of
      phosphorylation during mitotic entry.
AB  - Chromosome segregation requires the ordered separation of the newly replicated
      chromosomes between the two daughter cells. In most cells, this requires nuclear
      envelope (NE) disassembly during mitotic entry and its reformation at mitotic
      exit. Nuclear envelope breakdown (NEB) results in the mixture of two cellular
      compartments. This process is controlled through phosphorylation of multiple
      targets by cyclin-dependent kinase 1 (Cdk1)-cyclin B complexes as well as other
      mitotic enzymes. Experimental evidence also suggests that nucleo-cytoplasmic
      transport of critical cell cycle regulators such as Cdk1-cyclin B complexes or
      Greatwall, a kinase responsible for the inactivation of PP2A phosphatases, plays
      a major role in maintaining the boost of mitotic phosphorylation thus preventing
      the potential mitotic collapse derived from NEB. These data suggest the relevance
      of nucleo-cytoplasmic transport not only to communicate cytoplasmic and nuclear
      compartments during interphase, but also to prepare cells for the mixture of
      these two compartments during mitosis. 

PMID- 24889071
TI  - Protein expression changes during cotton fiber elongation in response to drought
      stress and recovery.
AB  - An investigation to better understand the molecular mechanism of cotton
      (Gossypium hirsutum L.) fiber elongation in response to drought stress and
      recovery was conducted using a comparative proteomics analysis. Cotton plants
      (cv. NuCOTN 33B) were subjected to water deprivation for 10 days followed by a
      recovery period (with watering) of 5 days. The temporal changes in total proteins
      in cotton fibers were examined using 2DE. The results revealed that 163 proteins
      are significantly drought responsive. MS analysis led to the identification of
      132 differentially expressed proteins that include some known as well as some
      novel drought-responsive proteins. These drought responsive fiber proteins in
      NuCOTN 33B are associated with a variety of cellular functions, i.e. signal
      transduction, protein processing, redox homeostasis, cell wall modification,
      metabolisms of carbon, energy, lipid, lignin, and flavonoid. The results suggest
      that the enhancement of the perception of drought stress, a new balance of the
      metabolism of the biosynthesis of cell wall components and cytoskeleton
      homeostasis plays an important role in the response of cotton fibers to drought
      stress. Overall, the current study provides an overview of the molecular
      mechanism of drought response in cotton fiber cells.

PMID- 24889073
TI  - Cytochrome P450 3A-mediated metabolism of the topoisomerase I inhibitor 9
      aminocamptothecin: impact on cancer therapy.
AB  - The metabolism of 9-aminocamptothecin (9-AC) was investigated in human and rat
      liver microsomes. In both species 9-AC was almost exclusively biotransformed to
      dihydroxy-9-AC (M1) and monohydroxy-9-AC (M2). The enzymatic efficiencies of the
      formation of M1 and M2 (V(max)/K(m)) were 1.7- and 2.7-fold higher in rat than in
      human liver microsomes indicating species-related differences in 9-AC
      hydroxylation. Incubation in the presence of human recombinant cytochrome P450
      (CYP) enzymes demonstrated that the formation of M1 and M2 is mainly catalyzed by
      CYP3A4 and only to a minor extent by extrahepatic CYP1A1. The predominant role of
      CYP3A4 was further supported by a dramatic inhibition of metabolite formation in
      the presence of the CYP3A4 substrates troleandomycin and ketoconazole.
      Experiments conducted in isolated perfused rat livers further demonstrated that
      biliary excretion of 9-AC, M1 and M2 during 60 min of perfusion was pronounced
      and accounted for 17.7+/-2.59, 0.05+/-0.01 and 2.75+/-0.14% of total 9-AC applied
      to the liver, respectively. In summary, this study established that CYP3A
      dependent hydroxylation is the main metabolic pathway for 9-AC in rat and human
      liver, which have to be taken into consideration during cancer therapy of
      patients.

PMID- 24889075
TI  - Re: associations between premature ejaculation, lower urinary tract symptoms, and
      erectile dysfunction in middle-aged Korean policemen.

PMID- 24889074
TI  - Au2S(x)/CdS nanorods by cation exchange: mechanistic insights into the
      competition between cation-exchange and metal ion reduction.
AB  - It is well known that metals with higher electron affinity like Au tend to
      undergo reduction rather than cation-exchange. It is experimentally shown that
      under certain conditions cation-exchange is dominant over reduction.
      Thermodynamic calculation further consolidates the understanding and paves the
      way for better predictability of cation-exchange/reduction reactions for other
      systems. 

PMID- 24889076
TI  - Fire and home range expansion: a behavioral response to burning among savanna
      dwelling vervet monkeys (Chlorocebus aethiops).
AB  - The behavioral adaptations of primates to fire-modified landscapes are of
      considerable interest to anthropologists because fire is fundamental to life in
      the African savanna-the setting in which genus Homo evolved. Here we report the
      behavioral responses of a savanna-dwelling primate, vervet monkeys (Chlorocebus
      aethiops), to fire-induced ecological change. Using behavioral and spatial data
      to characterize ranging patterns prior to and postburn and between burn and
      nonburn years, we show that these primates inhabiting small, spatially bound,
      riverine habitats take advantage of newly burned savanna landscapes. When
      subjects encountered controlled fires, they did not flee but instead avoided the
      path of the fire seemingly unbothered by its approach. After fire, the primates'
      home range expanded into newly burned but previously unused areas. These results
      contribute to understanding the response of non-human primates to fire-modified
      landscapes and can shed light on the nature and scope of opportunities and
      constraints posed by the emergence of fire-affected landscapes in the past.
      Results also expose deficiencies in our knowledge of fire-related behavioral
      responses in the primate lineage and highlight the need for further investigation
      of these responses as they relate to foraging opportunities, migration, resource
      use, and especially fire-centric adaptations in our own genus.

PMID- 24889077
TI  - The school breakfast program: a view of the present and preparing for the future
      a commentary.

PMID- 24889078
TI  - Examining the association between bullying and adolescent concerns about teen
      dating violence.
AB  - BACKGROUND: The school environment is an important context for understanding risk
      factors for teen dating violence. This study seeks to add to the growing
      literature base linking adolescent experiences with bullying and involvement with
      teen dating violence. METHODS: Data were collected from 27,074 adolescents at 58
      high schools via a Web-based survey. RESULTS: Three-level hierarchical linear
      models indicated that adolescents who had been bullied were more concerned about
      both physical and emotional dating violence among students at their school.
      Schools that were perceived by students as safer were rated as having lower
      levels of teen dating violence. Older students and male students consistently
      reported greater concerns about dating violence. CONCLUSIONS: These results
      suggest that adolescents who experience bullying may also have concerns about
      violence in teen dating relationships. Findings also indicate that schools
      perceived as being unsafe may be an important context for targeting dating
      violence prevention efforts.

PMID- 24889079
TI  - Are students with asthma at increased risk for being a victim of bullying in
      school or cyberspace? Findings from the 2011 Florida youth risk behavior survey.
AB  - BACKGROUND: Adolescents with asthma are at risk for psychological and behavioral
      problems. The aim of this study was to determine whether high school students
      with asthma are at increased risk for bullying in school and cyberspace, and to
      explore the role of depressive symptoms in moderating this association. METHODS:
      A secondary data analysis was completed with the 2011 Florida Youth Risk Behavior
      Survey. Participant included a random sample of adolescents in grades 9 through
      12 who attended public high schools in Florida. Descriptive and inferential
      statistics were conducted using SPSS software. RESULTS: We examined data from
      6212 high school adolescents and found a significant relationship between current
      asthma and cyberbullying in adolescents. Of the sample diagnosed with asthma,
      15.6% reported bullying and 17% cyberbullying (versus 10.2% and 11% of
      nonasthmatics). We further examined data using depressive symptoms as a mediating
      and moderating variable and found significance on all accounts. CONCLUSIONS:
      Adolescents with asthma are at increased risk for being victims of bullying in
      school and cyberspace. Our findings suggest that adolescents with asthma who also
      report depressive symptoms are particularly at high risk for bullying than
      adolescents with asthma who did not report depressive symptoms. Efforts to
      increase education and decrease all types of bullying at the high school level
      for both students with and without asthma are warranted.

PMID- 24889080
TI  - Optimizing violence prevention programs: an examination of program effectiveness
      among urban high school students.
AB  - BACKGROUND: While demand for youth violence prevention programs increases, the
      ability of the school-day schedule to accommodate their time requirements has
      diminished. Viable school-based prevention programs must strike a balance between
      brevity and effectiveness. This article reports results from an effectiveness
      trial of a 12-session curriculum-based universal violence prevention program that
      promotes healthy conflict resolution skills among urban adolescents. METHODS:
      Using a review of program record data and a multisite quasi-experimental study
      design, we examined the effectiveness of a New York City-based violence
      prevention program entitled the Violence Prevention project (VPP) optimized to
      meet school needs. We analyzed survey data from 1112 9th- and 10th-grade students
      in 13 New York City public high schools across 4 consecutive school years. Both
      participants and nonparticipants were surveyed. RESULTS: Review of program record
      data indicated that the program was implemented with acceptable fidelity to the
      core component structure, and that participant responsiveness to the model was
      high. Multilevel modeling indicated that VPP participation was protective for
      academic self-concept and promoted conflict resolution skills. CONCLUSIONS:
      Findings indicate that semester-long violence prevention programs optimized to
      meet the needs of a typical high school can be effective at promoting healthy
      conflict resolution skills in urban adolescents.

PMID- 24889081
TI  - Investigating mental fitness and school connectedness in Prince Edward Island and
      New Brunswick, Canada.
AB  - BACKGROUND: As youth struggle with anxiety and depression, promoting positive
      mental fitness is a primary concern. Canadian school-based mental health programs
      that focus on positive psychology and positive mental health initiatives
      emphasize safe and supportive environments, student engagement, resilience, and
      self-determination. This study examined predictors of mental fitness and its 3
      components (autonomy, competence, and relatedness). METHODS: School Health Action
      Planning and Evaluation System-Prince Edward Island (SHAPES-PEI) and the New
      Brunswick Student Wellness Survey (NB SWS) are data collection and feedback
      systems that survey youth about 4 health behaviors. Grade 7-12 students in Prince
      Edward Island (N = 3318) and New Brunswick (N = 7314) completed a mental fitness
      questionnaire in 2008-2009 (PEI) and 2006-2007 (NB). Four linear regression
      models were conducted to examine student characteristics associated with mental
      fitness, autonomy, competence, and relatedness. RESULTS: Positive associations
      were found between school connectedness (p < .0001) and mental fitness, as well
      as autonomy, competence, and relatedness. There were also significant
      relationships between affect, pro-social and antisocial behaviors, tried smoking,
      and mental fitness. CONCLUSION: A better understanding of adolescent health and
      its predictors is needed. By identifying core parameters for mental fitness, we
      can inform how to address students' needs through appropriate programs and
      policies supporting healthy school environments.

PMID- 24889082
TI  - Profits, commercial food supplier involvement, and school vending machine snack
      food availability: implications for implementing the new competitive foods rule.
AB  - BACKGROUND: The 2013-2014 school year involved preparation for implementing the
      new US Department of Agriculture (USDA) competitive foods nutrition standards. An
      awareness of associations between commercial supplier involvement, food vending
      practices, and food vending item availability may assist schools in preparing for
      the new standards. METHODS: Analyses used 2007-2012 questionnaire data from
      administrators of 814 middle and 801 high schools in the nationally
      representative Youth, Education, and Society study to examine prevalence of
      profit from and commercial involvement with vending machine food sales, and
      associations between such measures and food availability. RESULTS: Profits for
      the school district were associated with decreased low-nutrient, energy-dense
      (LNED) food availability and increased fruit/vegetable availability. Profits for
      the school and use of company suppliers were associated with increased LNED
      availability; company suppliers also were associated with decreased
      fruit/vegetable availability. Supplier "say" in vending food selection was
      associated with increased LNED availability and decreased fruit/vegetable
      availability. CONCLUSIONS: Results support (1) increased district involvement
      with school vending policies and practices, and (2) limited supplier "say" as to
      what items are made available in student-accessed vending machines. Schools and
      districts should pay close attention to which food items replace vending machine
      LNED foods following implementation of the new nutrition standards.

PMID- 24889083
TI  - Improving pre-service elementary teachers' self-reported efficacy for using the
      professional teacher standards in health education.
AB  - BACKGROUND: The effectiveness of health education methods courses for pre-service
      elementary teachers has not been assessed for improving the pre-service
      elementary teacher's self-efficacy for using the professional teacher standards
      in health education (PTSHE). METHODS: A quasi-experimental design was used to
      assess pre-service elementary teachers' self-efficacy toward using the PTSHE.
      Four institutions whose elementary education programs provide a health education
      methods course were recruited to participate in the study. Students were
      recruited to participate and they completed the Pre-service Health Education
      National Standards Self-efficacy (PHENSS) Scale at the beginning and end of the
      semester. Data were analyzed using SPSS (version 15) software. RESULTS: A
      significant increase in the PHENSS Scale scores indicated that a 3-credit health
      education methods course could improve the pre-service elementary teacher's self
      efficacy to use the national standards in their teaching of health education.
      Further analysis indicated statistically significant improvement of the
      participants' PHENSS scores in 2 of the 7 standards. CONCLUSION: Teacher self
      efficacy can be a useful measure of the pre-service elementary teachers' ability
      to use the national standards for health education. The design of the methods
      course may affect the PHENSS scores.

PMID- 24889084
TI  - Carrots and sticks: compliance provisions in state competitive food laws-examples
      for state and local implementation of the updated USDA standards.
AB  - BACKGROUND: Competitive foods remain prevalent in schools even though the
      majority of states' laws have addressed this for several years. Whereas updated
      federal standards take effect during school year 2014-2015, aspects of
      competitive food regulation will remain relegated to the states and districts and
      concerns exist about compliance with the federal standards. This study examined
      compliance provisions codified into state law that focused on incentives,
      monetary penalties, or contracts which could provide examples for other
      jurisdictions. METHODS: Codified statutory and administrative laws effective as
      of January 2013 for all 50 states and the District of Columbia were compiled
      using Boolean searches in Lexis-Nexis and Westlaw. All laws were analyzed by 2
      study authors to determine the presence and components of relevant provisions.
      RESULTS: Eighteen states' laws contained compliance mechanisms including
      financial and/or programmatic incentives (5 states), contract provisions (11
      states), and monetary penalties for noncompliance (7 states). Five states' laws
      contained a combination of approaches. CONCLUSIONS: Compliance measures help to
      strengthen competitive food laws by providing state agencies with an enforcement
      mechanism. Enforcing such provisions will help to create healthier school
      environments. This study will provide useful insight for governments at all
      levels as they implement competitive food laws.

PMID- 24889085
TI  - Emerging roles of metal solute carriers in cancer mechanisms and treatment.
AB  - The literature concerning the roles of metal transporting solute carriers in the
      development and progression of human cancer, and in the delivery of metal
      containing anticancer drugs, chemical carcinogens and imaging agents, is
      reviewed. A range of different solute carrier families, including members from
      the SLC2A, SLC11A, SLC22A, SLC25A, SLC30A, SLC31A, SLC39A, SLC40A, SLC47A and
      SLCO1B families, and various metal substrates, including arsenic, copper,
      gadolinium, iron, platinum and zinc, have been implicated in these cancer-related
      transport processes. For example, the transport of platinum-based anticancer
      drugs has been reported to be influenced by the expression and activities of OCT1
      3 (SLC22A1-3), OCTN1/2 (SLC22A4/5), CTR1/2 (SLC31A1/2) and MATE1/2 (SLC47A1/2)
      solute carriers. As another example, solute carriers mediate control over the
      availability of endogenous metal ions, such as copper, iron and zinc, may have
      key roles in regulating tumour angiogenesis, cell proliferation, epithelial-to
      mesenchymal transition and aberrant MAPK and STAT-3 signal transduction in
      cancer. In conclusion, emerging mechanisms involving metal transporting solute
      carriers are being defined and seem likely to make major contributions to cancer
      development and progression, and to the delivery of anticancer and tumour imaging
      agents.

PMID- 24889086
TI  - Stepping accuracy and visuomotor control among older adults: effect of target
      contrast and refractive blur.
AB  - PURPOSE: Older adults have increased visual impairment, including refractive blur
      from presbyopic multifocal spectacle corrections, and are less able to extract
      visual information from the environment to plan and execute appropriate stepping
      actions; these factors may collectively contribute to their higher risk of falls.
      The aim of this study was to examine the effect of refractive blur and target
      visibility on the stepping accuracy and visuomotor stepping strategies of older
      adults during a precision stepping task. METHODS: Ten healthy, visually normal
      older adults (mean age 69.4 +/- 5.2 years) walked up and down a 20 m indoor
      corridor stepping onto selected high and low contrast targets while viewing under
      three visual conditions: best-corrected vision, +2.00 DS and +3.00 DS blur; the
      order of blur conditions was randomised between participants. Stepping accuracy
      and gaze behaviours were recorded using an eyetracker and a secondary hand-held
      camera. RESULTS: Older adults made significantly more stepping errors with
      increasing levels of blur, particularly exhibiting under-stepping (stepping more
      posteriorly) onto the targets (p < 0.05), while visuomotor stepping strategies
      did not significantly alter. Stepping errors were also significantly greater for
      the low compared to the high contrast targets and differences in visuomotor
      stepping strategies were found, including increased duration of gaze and
      increased interval between gaze onset and initiation of the leg swing when
      stepping onto the low contrast targets. CONCLUSIONS: These findings highlight
      that stepping accuracy is reduced for low visibility targets, and for high levels
      of refractive blur at levels typically present in multifocal spectacle
      corrections, despite significant changes in some of the visuomotor stepping
      strategies. These findings highlight the importance of maximising the contrast of
      objects in the environment, and may help explain why older adults wearing
      multifocal spectacle corrections exhibit an increased risk of falling.

PMID- 24889087
TI  - Ecological divergence among colour morphs mediated by changes in spatial network
      structure associated with disturbance.
AB  - Differences in individual behaviour affect social interactions and contribute to
      the spatial structuring of animal populations. However, disturbance should also
      affect spatial networks by altering habitat heterogeneity and resource
      availability. Variation in resource availability should perturb the frequency and
      nature of social and ecological interactions within a population by affecting the
      spatial distribution of individuals. In disturbed habitats where resources are
      limiting, spatial relationships should reflect behavioural differences among
      individuals, with higher-quality resources controlled by dominant individuals. In
      contrast, all individuals may exploit preferred resources in resource-rich
      habitats. Environmental variation and population reorganization may also result
      in variation in morphological, behavioural and ecological traits, which
      ultimately affect fitness. We addressed these considerations for male tree
      lizards (Urosaurus ornatus) at three sites that differ in levels of disturbance.
      The habitats at these localities differed in the availability of live trees, the
      preferred microhabitat of U. ornatus. In addition, male U. ornatus exhibits a
      polymorphism in dewlap colour linked with differences in aggression, which should
      influence their position in a network and access to resources. We applied a
      network framework to characterize the spatial organization of male morphs at each
      site and quantified male aggressive behaviour in the laboratory. We also compared
      body size, body condition, number of bite marks, parasite load and the
      microhabitat use and diet, of males among the sites. We detected no significant
      differences in spatial network structure between unburned and infrequently burned
      sites. However, at a frequently burned site, the network shifted towards
      geographically closer, heteromorphic male neighbour associations. Males at this
      site were also larger, more aggressive and had more bite marks but fewer
      parasites than males at the other sites. Moreover, we detected divergence in
      microhabitat use and diet among the morphs at the frequently burned site that
      reflected the shift in spatial network structure and differences in morph
      behaviour. That is, only more aggressive morphs usurped trees and consumed prey
      from higher trophic levels. We conclude that environmental variation may
      influence animal spatial network structure. Jointly, behavioural and
      environmental variation may promote despotic social dynamics and ecological
      divergence in resource-limited habitats. 

PMID- 24889088
TI  - Germacrone inhibits the proliferation of glioma cells by promoting apoptosis and
      inducing cell cycle arrest.
AB  - Germacrone is one of the major bioactive components of the traditional Chinese
      Medicinal plant Curcuma aromatica Salisb. and has been shown to possess anti
      tumor properties. In the present study, the anti-proliferative effect of
      germacrone on human glioma cells and the molecular mechanism underlying its
      cytotoxicity were investigated. Treatment of the U87 and U251 human glioma cell
      lines with germacrone inhibited the cell proliferation in a dose- and time
      dependent manner as assessed by MTT assay, while significantly lower effects were
      observed on normal human astrocytes. Flow cytometric analysis and DNA
      fragmentation revealed that germacrone promoted apoptosis of glioma cells,
      associated with an increased expression of p53 and bax and decreased expression
      of bcl-2. Furthermore, flow cytometric cell cycle analysis revealed that
      germacrone induced G1 phase arrest, associated with an obvious decrease in the
      expression of cyclin D1 and CDK2 and an increased expression of p21. In
      conclusion, the present study suggested that germacrone may be a novel potent
      chemopreventive drug candidate for gliomas via regulating the expression of
      proteins associated with apoptosis and G1 cell cycle arrest. 

PMID- 24889089
TI  - Interference of flavonoids with fluorescent intracellular probes: methodological
      implications in the evaluation of the oxidative burst by flow cytometry.
AB  - The evaluation of oxidative burst is particularly relevant in many pathological
      and subclinical conditions. Flow cytometry provides quick and accurate measures
      of the reactive oxygen species production by leukocytes in most situations.
      However, spurious results, related to probes' efflux may be observed in several
      instances. Many factors affect the evaluation of the oxidative burst with
      fluorescent probes that require intracellular deacetylation and could be
      substrate of the multidrug resistance proteins (MDR). After discussing the
      implications of the efflux of fluorophores in the normalization strategies in
      flow cytometry assays, we have pointed out the possible interference of
      flavonoids with fluorescet probes' staining and signal. We have also reviewed the
      results from human intervention studies regarding the evaluation of oxidative
      burst with these probes. In vitro, at concentrations close to post-ingestion
      circulating levels, some flavonoids and their metabolites could interfere with
      probes' staining and fluorescence signal through different mechanisms, such as
      the inhibition of esterases, the modulation of the MDR-mediate efflux of probe
      and the inhibition of the oxidation of probe. These effects may explain the
      contrasting results obtained by human intervention studies. Finally, also
      inflammatory state or the use of drugs substrate of MDR proteins could affect the
      evaluation of the oxidative burst with intracellular probes.

PMID- 24889090
TI  - Travel-related shigellosis in Quebec, Canada: an analysis of risk factors.
AB  - BACKGROUND: Travel-related shigellosis is not well documented in Canada although
      it is frequently acquired abroad and can cause severe disease. OBJECTIVES: To
      describe the epidemiology of travel-related cases of shigellosis for Quebec
      (Canada) and to identify high-risk groups of travelers. METHOD AND DATA SOURCES:
      We performed a random sampling of 335 shigellosis cases (from a total of 760
      cases) reported in the provincial database of reportable diseases from January 1,
      2004, to December 31, 2007. Each case was analyzed according to information
      available in the epidemiology questionnaire. Total number of trips by region from
      Statistics Canada was used as denominator to estimate the risk according to
      region of travel. RESULTS: Annually, between 43 and 54% of the shigellosis cases
      were reported in travelers, 45% of whom were aged between 20 and 44 years.
      Children under 11 years accounted for nearly 16% of cases, but represent only 4%
      of travelers. Most cases in travelers were serogroups Shigella sonnei (50%) or
      Shigella flexneri (45%). Almost 31% of cases were reported between January and
      March. The majority (64%) were acquired in Central America, Mexico, or the
      Caribbean. However, the Indian subcontinent, Africa, and South America had the
      highest ratio of number of cases per number of trips. Tourists represented 76% of
      the cases; 62% of them had traveled for <2 weeks. At least 15% of cases among
      travelers were hospitalized. CONCLUSIONS: In Quebec, travel-related cases of
      shigellosis represent a large burden of total cases. Short-term travelers are at
      risk, as well as young children. The majority of cases occur in the winter
      months, corresponding to the peak of travel to "sunshine destinations."
      Continuous efforts should be made to encourage all travelers to seek pre-travel
      care, and to inform primary care practitioners of health risks faced by their
      patients abroad, even for those going to resorts.

PMID- 24889091
TI  - Hybridisation and introgression between Brassica napus and B. rapa in the
      Netherlands.
AB  - We used flow cytometry, chromosome counting and AFLP markers to investigate gene
      flow from the crop plant oilseed rape, Brassica napus (AACC) to wild B. rapa (AA)
      in the Netherlands. From 89 B. napus source populations investigated, all near
      cropping fields or at transhipment sites, only 19 contained a B. rapa population
      within a 2.5-km radius. During our survey we found only three populations with F1
      hybrids (AAC), as recognized by their nine extra chromosomes and by flow
      cytometry. These hybrids were all collected in mixed populations where the two
      species grew in close proximity. Populations with F1 hybrids were not close to
      crops, but instead were located on road verges with highly disturbed soils, in
      which both species were probably recruited from the soil seed bank. Many plants
      in the F2, BC1 or higher backcrosses are expected to carry one to eight C
      chromosomes. However, these plants were not observed among the hybrids. We
      further investigated introgression with molecular markers (AFLP) and compared
      sympatric B. rapa populations (near populations of B. napus) with control
      populations of B. rapa (no B. napus within at least 7 km). We found no difference
      between sympatric and control populations in the number of C markers in B. rapa,
      nor did we find that these sympatric populations closely resembled B. napus. Our
      data show that hybrids occur but also suggest no recent introgression of alleles
      from the crop plant B. napus into wild B. rapa in the Dutch populations studied. 

PMID- 24889092
TI  - Satisfaction of farm animal behavioral needs in behaviorally restricted systems:
      reducing stressors and environmental enrichment.
AB  - In modern intensive husbandry, systems often restrict farm animal behavior.
      Behavioral needs will be generated by external stimuli such as stressors deriving
      from environmental factors or the method of animal care, or some internal factor
      in farm animals. This means that behavioral restriction would induce
      maladaptation to stressors or chronic stress. Such a risk of behavioral
      restriction degrades an animal's physical and mental health and leads to economic
      loss at a farm. Methods to reduce the risk of behavioral restrictions are to
      ameliorate the source of a stressor through adequate animal management or to
      carry out environmental enrichment. This review is intended to describe the
      relation between animal management and behavioral needs from the perspective of
      animal motivation. 

PMID- 24889094
TI  - Biofilm-forming skin microflora bacteria are resistant to the bactericidal action
      of disinfectants used during blood donation.
AB  - BACKGROUND: A one-step skin disinfection method containing 2% chlorhexidine
      gluconate (CHG) and 70% isopropyl alcohol (IPA) is currently used by blood
      suppliers worldwide. Reports of bacterially contaminated platelet concentrates
      (PCs) indicate that skin disinfection is not fully effective. Approximately 20%
      of skin microflora exist as surface-attached aggregates (biofilms), known for
      displaying increased resistance to disinfectants. This study was aimed at
      determining whether skin microflora biofilm-positive Staphylococcus epidermidis
      and Staphylococcus capitis are resistant to CHG and/or IPA. STUDY DESIGN AND
      METHODS: Free-floating cells and mono or dual (1 : 1 ratio) biofilms of S.
      epidermidis and S. capitis were exposed to CHG, IPA, or CHG/IPA for 30 seconds,
      simulating skin disinfection practices. Residual viable cells were quantified by
      colony counting. Morphology of disinfectant-treated S. epidermidis biofilms was
      examined by scanning electron microscopy. Treated S. epidermidis and S. capitis
      biofilms were inoculated into PCs and bacterial concentrations were determined on
      Days 0 and 5 of storage. RESULTS: Treatment of staphylococcal biofilm cells with
      all disinfectants caused cell damage and significant reduction in viability, with
      CHG/IPA being the most effective. However, biofilms were significantly more
      resistant to treatment than free-floating cells. Disinfectant-treated S.
      epidermidis proliferated better in PCs than S. capitis, especially when grown as
      monospecies biofilms. CONCLUSION: Although CHG/IPA is effective in reducing the
      viability of S. epidermidis and S. capitis biofilms, these organisms are not
      completely eliminated. Furthermore, disinfectant-treated staphylococcal biofilms
      multiply well in PCs. These results demonstrate that the biofilm-forming
      capability of the skin microflora reduces the bactericidal efficiency of blood
      donor skin disinfectants.

PMID- 24889095
TI  - Enhancement of ginsenoside biosynthesis and secretion by Tween 80 in Panax
      ginseng hairy roots.
AB  - We evaluated the effect of Tween 80 permeabilization on ginsenoside secretion in
      Panax ginseng hairy roots. Tween 80 (1.2%, w/v) had no significant effect on
      hairy root vitality. After a 25-day treatment with Tween 80, approximately 76% of
      the total ginsenosides was released into the surrounding medium. In the case of
      control, the ginsenosides secreted into the medium were negligible. Furthermore,
      when compared with control, the level of total ginsenosides was enhanced by
      approximately threefold under Tween treatment. Additionally, secretion of the
      typical ginsenoside monomers including Rb1 , Rg1 , and Re was analyzed,
      indicating that the most of them were released into the medium. Moreover, it was
      observed that dammarenediol synthase, a key enzyme involved in ginsenoside
      biosynthesis, was upregulated at both gene expression and enzyme activity levels.
      The expression of genes CYP716A47 and CYP716A53v2 encoding Cyt P450 enzymes
      catalyzing the formation of protopanaxadiol from dammarenediol and
      protopanaxatriol from protopanaxadiol, respectively, was slightly upregulated.
      These results clearly demonstrated that Tween 80 could act not only as an
      efficient permeabilizer to enhance ginsenoside secretion from the hairy roots,
      but also as an elicitor to promote the biosynthesis of ginsenoside. 

PMID- 24889093
TI  - Structure-based simulations reveal concerted dynamics of GPCR activation.
AB  - G protein-coupled receptors (GPCRs) are a vital class of proteins that transduce
      biological signals across the cell membrane. However, their allosteric activation
      mechanism is not fully understood; crystal structures of active and inactive
      receptors have been reported, but the functional pathway between these two states
      remains elusive. Here, we use structure-based (Go-like) models to simulate
      activation of two GPCRs, rhodopsin and the beta2 adrenergic receptor (beta2AR).
      We used data-derived reaction coordinates that capture the activation mechanism
      for both proteins, showing that activation proceeds through quantitatively
      different paths in the two systems. Both reaction coordinates are determined from
      the dominant concerted motions in the simulations so the technique is broadly
      applicable. There were two surprising results. First, the main structural changes
      in the simulations were distributed throughout the transmembrane bundle, and not
      localized to the obvious areas of interest, such as the intracellular portion of
      Helix 6. Second, the activation (and deactivation) paths were distinctly
      nonmonotonic, populating states that were not simply interpolations between the
      inactive and active structures. These transitions also suggest a functional
      explanation for beta2AR's basal activity: it can proceed through a more broadly
      defined path during the observed transitions.

PMID- 24889096
TI  - CD14 polymorphisms, microbial exposure and allergic diseases: a systematic review
      of gene-environment interactions.
AB  - Asthma and allergy may develop as a result of interactions between environmental
      factors and the genetic characteristics of an individual. This review aims to
      summarize the available evidence for, and potential effects of, an interaction
      between polymorphisms of the CD14 gene and exposure to microbes on the risk of
      asthma and allergic diseases. We searched PubMed, MEDLINE and Global Health
      databases, finding 12 articles which met inclusion criteria. Most studies
      reported a significant interaction between CD14 polymorphisms and microbial
      exposure. When stratified by age at microbial exposure (early life vs adult
      life), there was evidence of a protective effect of gene-environment interaction
      against atopy in children, but not adults. We also found different effects of
      interaction depending on the type of microbial exposures. There was no strong
      evidence for asthma and eczema. Future studies should consider a three-way
      interaction between CD14 gene polymorphisms, microbial exposures and the age of
      exposure. 

PMID- 24889097
TI  - Development and application of primers for the class Dehalococcoidia (phylum
      Chloroflexi) enables deep insights into diversity and stratification of subgroups
      in the marine subsurface.
AB  - Bacteria of the class Dehalococcoidia (DEH) (phylum Chloroflexi) are widely
      distributed in the marine subsurface and are especially prevalent in deep marine
      sediments. Nevertheless, little is known about the specific distributions of DEH
      subgroups at different sites and depths. This study therefore specifically
      examined the distributions of DEH through depths of various marine sediment cores
      by quantitative PCR and pyrosequencing using newly designed DEH 16S rRNA gene
      targeting primers. Quantification of DEH showed populations may establish in
      shallow sediments (i.e. upper centimetres), although as low relative proportions
      of total Bacteria, yet often became more prevalent in deeper sediments.
      Pyrosequencing revealed pronounced diversity co-exists within single
      biogeochemical zones, and that clear and sometimes abrupt shifts in relative
      proportions of DEH subgroups occur with depth. These shifts indicate varying
      metabolic properties exist among DEH subgroups. The distributional changes in DEH
      subgroups with depth may be related to a combination of biogeochemical factors
      including the availability of electron acceptors such as sulfate, the composition
      of organic matter and depositional regimes. Collectively, the results suggest DEH
      exhibit wider metabolic and genomic diversity than previously recognized, and
      this contributes to their widespread occurrence in the marine subsurface. 

PMID- 24889098
TI  - Retinofugal projections in the mouse.
AB  - The laboratory mouse is increasingly a subject for visual system investigation,
      but there has been no comprehensive evaluation of this species' visual
      projections. Here, projections were visualized and mapped following intraocular
      injection of cholera toxin B subunit. Tissue was processed using standard
      procedures applied to 30 MUm free-floating sections with diaminobenzidine as the
      chromogen. The mouse retina projects to ~46 brain regions, including 14 not
      previously described in this species. These include two amygdaloid nuclei, the
      horizontal limb of the diagonal band, the paraventricular hypothalamic nucleus,
      several visual thalamic nuclei, the paranigral nucleus, several pretectal nuclei,
      and the dorsal cortex of the inferior colliculus. Dense retinal patches were also
      observed in a narrow portion of the ipsilateral intermediate layer of the
      superior colliculus. The superior fasciculus of the accessory optic tract, which
      innervates the medial terminal nucleus, was also determined to be a terminal zone
      throughout its length. The results are compared with previous descriptions of
      projections from mouse intrinsically photoreceptive retinal ganglion cells, and
      with data from the hamster, Nile grass rat, and laboratory rat. The retinal
      projection patterns are similar in all four species, although there are many
      differences with respect to the details. The specific visual functions of most
      retinorecipient areas are unknown, but there is substantial convergence of
      retinal projections onto regions concerned with olfaction and audition.

PMID- 24889099
TI  - Extreme heat and cultural and linguistic minorities in Australia: perceptions of
      stakeholders.
AB  - BACKGROUND: Despite acclimatisation to hot weather, many individuals in Australia
      are adversely affected by extreme heat each summer, placing added pressure on the
      health sector. In terms of public health, it is therefore important to identify
      vulnerable groups, particularly in the face of a warming climate. International
      evidence points to a disparity in heat-susceptibility in certain minority groups,
      although it is unknown if this occurs in Australia. With cultural diversity
      increasing, the aim of this study was to explore how migrants from different
      cultural backgrounds and climate experiences manage periods of extreme heat in
      Australia. METHODS: A qualitative study was undertaken across three Australian
      cities, involving interviews and focus groups with key informants including
      stakeholders involved in multicultural service provision and community members.
      Thematic analysis and a framework approach were used to analyse the data.
      RESULTS: Whilst migrants and refugees generally adapt well upon resettlement,
      there are sociocultural barriers encountered by some that hinder environmental
      adaptation to periods of extreme heat in Australia. These barriers include
      socioeconomic disadvantage and poor housing, language barriers to the access of
      information, isolation, health issues, cultural factors and lack of
      acclimatisation. Most often mentioned as being at risk were new arrivals, people
      in new and emerging communities, and older migrants. CONCLUSIONS: With increasing
      diversity within populations, it is important that the health sector is aware
      that during periods of extreme heat there may be disparities in the adaptive
      capacity of minority groups, underpinned by sociocultural and language-based
      vulnerabilities in migrants and refugees. These factors need to be considered by
      policymakers when formulating and disseminating heat health strategies.

PMID- 24889101
TI  - Discussion.

PMID- 24889100
TI  - Insulin receptor antibody-iduronate 2-sulfatase fusion protein: pharmacokinetics,
      anti-drug antibody, and safety pharmacology in Rhesus monkeys.
AB  - Mucopolysaccharidosis (MPS) Type II is caused by mutations in the gene encoding
      the lysosomal enzyme, iduronate 2-sulfatase (IDS). The majority of MPSII cases
      affect the brain. However, enzyme replacement therapy with recombinant IDS does
      not treat the brain, because IDS is a large molecule drug that does not cross the
      blood-brain barrier (BBB). To enable BBB penetration, IDS has been re-engineered
      as an IgG-IDS fusion protein, where the IgG domain is a monoclonal antibody (MAb)
      against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor
      mediated transport on the endogenous BBB insulin receptor, and the HIRMAb domain
      of the fusion protein acts as a molecular Trojan horse to ferry the fused IDS
      into brain from blood. The present study reports on the first safety pharmacology
      and pharmacokinetics study of the HIRMAb-IDS fusion protein. Juvenile male Rhesus
      monkeys were infused intravenously (IV) weekly for 26 weeks with 0, 3, 10, or 30
      mg/kg of the HIRMAb-IDS fusion protein. The plasma clearance of the fusion
      protein followed a linear pharmacokinetics profile, which was equivalent either
      with measurements of the plasma concentration of immunoreactive HIRMAb-IDS fusion
      protein, or with assays of plasma IDS enzyme activity. Anti-drug antibody (ADA)
      titers were monitored monthly, and the ADA response was primarily directed
      against the variable region of the HIRMAb domain of the fusion protein. No
      infusion related reactions or clinical signs of immune response were observed
      during the course of the study. A battery of safety pharmacology, clinical
      chemistry, and tissue histopathology showed no signs of adverse events, and
      demonstrate the safety profile of chronic treatment of primates with 3-30 mg/kg
      weekly IV infusion doses of the HIRMAb-IDS fusion protein.

PMID- 24889102
TI  - Audit of adult post-implant annual reviews and evaluation of patient-led review.
AB  - OBJECTIVES: Audits were carried out to assess the clinical effectiveness of
      historical annual review appointments and a new patient-led review system.
      METHODS: The written records of 100 patients who attended for an annual review
      appointment were retrospectively analysed. A further 50 patients who did not
      respond to the patient-led review offer letter were contacted to determine why
      they had not responded. The records of patients who subsequently attended for
      review were also analysed to evaluate their outcome. RESULTS: Ninety-one per cent
      of patients tested showed no change or an improvement in aided thresholds. Eighty
      nine per cent of patients tested showed no change or an improvement in speech
      discrimination scores. Ninety-three per cent of patients tested showed no change
      in impedances. Fifty-two per cent of patients required a map check and 36% of
      patients needed some equipment changed. One patient out of 100 needed referral to
      Ear, Nose and Throat (ENT). Twenty per cent of the patients who did not respond
      to the review offer letter reported they had not received the letter. The
      remainder did not require an appointment or did not understand the system.
      DISCUSSION: The results indicate that the majority of patients' implant and
      functional performance remains stable over time. The process of patient-led
      review has been optimized, so patients fully understand the system and are not
      missed if they do not receive the letter. CONCLUSION: Patient-led review allows
      patients to take more responsibility, so they can participate more proactively in
      the maintenance of their implant and the centre is able to focus their resources
      on the patients who need it.

PMID- 24889104
TI  - Radiological and Histological Evaluation of the Effects of Cortical Perforations
      on Bone Healing in Mandibular Onlay Graft Procedures.
AB  - BACKGROUND: Perforations of the cortical bone may be an advantage for the success
      of the autogenous bone graft procedure, but whether this perforation has a
      positive effect on the bone remains controversial. PURPOSE: This study evaluates
      the effects of cortical perforation of the autogenous bone block graft
      radiologically and histologically. MATERIALS AND METHODS: Seven adult pigs were
      used for this study. On the experimental side, cortical perforation at the host
      site was prepared, while no perforation was done on the control side. The
      specimens were evaluated, and the Wilcoxon signed-rank test was used for
      statistical analysis. RESULTS: In the radiological evaluation, the Wilcoxon
      signed-rank test indicated no significant differences in densities among the
      grafts (p = .23) with a mean of 4.29 +/- 0.951 for the unperforated graft side
      and 3.57 +/- 0.976 for the decorticated graft side. In histological evaluation,
      there was a significant difference in the thickness of the grafts between the
      groups (experimental group 3.71 +/- 1.286, control group: 4.71 +/- 0.488; p =
      .033). However, when the remodeling and osteoblastic activity in the grafts were
      measured, no significant differences were observed between the groups (p = 1 and
      p = .133, respectively). CONCLUSION: In augmentation with mandibular onlay bone
      grafts, cortical perforations in the recipient site make no distinct contribution
      to bone healing within 12 weeks.

PMID- 24889103
TI  - Non-speech oro-motor exercises in post-stroke dysarthria intervention: a
      randomized feasibility trial.
AB  - BACKGROUND: There has been little robust evaluation of the outcome of speech and
      language therapy (SLT) intervention for post-stroke dysarthria. Non-speech oro
      motor exercises (NSOMExs) are a common component of dysarthria intervention. A
      feasibility study was designed and executed, with participants randomized into
      two groups, in one of which NSOMExs were a component of the intervention
      programme. AIMS: To examine (1) operational feasibility of the programme; (2)
      participants' views of the programme; and (3) speech intelligibility,
      communication effectiveness and tongue and lip movement at four points (A1 and A2
      before, and A3 and A4 after intervention). METHODS & PROCEDURES: Thirty-nine
      participants were randomized into Group A (n=20) and Group B (n=19). Groups were
      equivalent at enrolment in demographic variables and A1 measures. Intervention
      was behavioural, delivered in eight home-based SLT sessions, and included
      practise of individually appropriate words, sentences and conversation, and for
      Group B also NSOMExs. Between-session practice was recorded in a diary. Data on
      speech intelligibility, effectiveness of communication in conversation, self
      rated situational communication effectiveness, and tongue and lip movement were
      collected at 8-week intervals, twice before and twice after intervention.
      Anonymous evaluation (AE) questionnaires were completed. OUTCOME & RESULTS: The
      recruited number was 20% below the target of 50. Thirty-six participants
      completed the intervention and 32 were followed through to A4. The programme was
      delivered to protocol and fidelity was verified. Thirty-four AEs were returned.
      These showed high satisfaction with the programme and its outcome. According to
      diary records from 32 participants, 59% carried out at least the recommended
      practice amount. Outcome measure performance across the four assessment points
      did not indicate any group effect. For the whole sample both externally rated and
      self-rated communication effectiveness measures showed statistically significant
      gains across the intervention period (A2/A3), which were maintained for 2 months
      after intervention (A2/A4). Non-intervention period changes (A1/A2 and A3/A4)
      were not present. There were no intervention-related gains in tongue and lip
      movement or speech intelligibility, but the latter is likely to be attributable
      to a ceiling effect on scores. CONCLUSIONS & IMPLICATIONS: The results indicate
      positive outcomes associated with a short period of behavioural SLT intervention
      in the post-stroke dysarthria population. The inclusion of NSOMExs, delivered in
      accordance with standard clinical practice, did not appear to influence outcomes.
      The results must be viewed in relation to the nature of feasibility study and
      provide a foundation for suitably powered trials.

PMID- 24889105
TI  - A new dual threshold time-over-threshold circuit for fast timing in PET.
AB  - Time-over-threshold (ToT) is attractive as a method of combined timing and energy
      encoding in positron emission tomography (PET) due to its simplicity in
      implementation and readout. However, conventional single threshold ToT has a
      nonlinear response and generally suffers from a tradeoff between timing and
      energy resolution. The resulting poor performance is not fit for applications
      requiring fast timing, such as time-of-flight (ToF) PET. In this work it is shown
      experimentally that by replacing single threshold ToT with a dual threshold
      method in a new compact circuit, excellent time resolution can be achieved (154
      ps FWHM for 3 * 3 * 5 mm(3) LYSO crystals), suitable for ToF. Dual threshold ToT
      timing results have been compared to a similar single threshold design,
      demonstrating that dual threshold ToT performance is far superior to that of
      single threshold ToT (154 ps versus 418 ps coincidence time resolution for the
      dual and single threshold cases, respectively). A method of correcting for
      nonlinearity in dual threshold ToT energy spectra is also demonstrated. 

PMID- 24889106
TI  - Recent development of antifouling polymers: structure, evaluation, and biomedical
      applications in nano/micro-structures.
AB  - Antifouling polymers have been proven to be vital to many biomedical applications
      such as medical implants, drug delivery, and biosensing. This review covers the
      major development of antifouling polymers in the last 2 decades, including the
      material chemistry, structural factors important to antifouling properties, and
      how to challenge or evaluate the antifouling performances. We then discuss the
      applications of antifouling polymers in nano/micro-biomedical applications in the
      form of nanoparticles, thin coatings for medical devices (e.g., artificial joint,
      catheter, wound dressing), and nano/microscale fibers.

PMID- 24889107
TI  - Additive manufacturing of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate]
      scaffolds for engineered bone development.
AB  - A wide range of poly(hydroxyalkanoate)s (PHAs), a class of biodegradable
      polyesters produced by various bacteria grown under unbalanced conditions, have
      been proposed for the fabrication of tissue-engineering scaffolds. In this study,
      the manufacture of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] (or
      PHBHHx) scaffolds, by means of an additive manufacturing technique based on a
      computer-controlled wet-spinning system, was investigated. By optimizing the
      processing parameters, three-dimensional scaffolds with different internal
      architectures were fabricated, based on a layer-by-layer approach. The resulting
      scaffolds were characterized by scanning electron microscopy, which showed good
      control over the fibre alignment and a fully interconnected porous network, with
      porosity in the range 79-88%, fibre diameter 47-76 um and pore size 123-789 um.
      Moreover, the resulting fibres presented an internal porosity connected to the
      external fibre surface as a consequence of the phase-inversion process governing
      the solidification of the polymer solution. Scaffold compressive modulus and
      yield stress and strain could be varied in a certain range by changing the
      architectural parameters. Cell-culture experiments employing the MC3T3-E1 murine
      pre-osteoblast cell line showed good cell proliferation after 21 days of culture.
      The PHBHHx scaffolds demonstrated promising results in terms of cell
      differentiation towards an osteoblast phenotype. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 24889108
TI  - Rhodium(I)-catalyzed cycloisomerization of benzylallene-alkynes through C-H
      activation.
AB  - The efficient Rh(I)-catalyzed cycloisomerization of benzylallene-alkynes produced
      the tricyclo[9.4.0.0(3,8)]pentadecapentaene skeleton through a C(sp2)-H bond
      activation in good yields. A plausible reaction mechanism proceeds via oxidative
      addition of the acetylenic C-H bond to Rh(I), an ene-type cyclization to the
      vinylidenecarbene-Rh(I) intermediate, and an electrophilic aromatic substitution
      with the vinylidenecarbene species. It was proposed based on deuteration and
      competition experiments.

PMID- 24889109
TI  - Effect of exposure to heatwave during blastocyst formation on reproductive
      performance of female rabbits.
AB  - We examined the effect of female exposure to heatwave during blastocyst formation
      on their reproductive performance and its effect on transcriptome in blastocyst
      and endometrial tissue. In this study, a total of 72 rabbit does were
      artificially inseminated and divided into two environmental groups 2 days later:
      does under conventional conditions (maintained between 14-22 degrees C, n = 29)
      and does heat stressed in a climatic chamber (maintained between 32-37 degrees C,
      n = 43). The heat-stressed group were kept under these conditions for 3 days and
      returned to conventional conditions thereafter. Five days post-insemination, 48
      does were slaughtered to collect blastocyst and endometrium samples. mRNA
      transcripts from OCT-4, VEGF, erbB3, Ifn-gamma, HSP70 and HSP90 were analysed by
      qRT-PCR. At day 12 of gestation, 24 females were examined by laparoscopy to
      evaluate implanted embryos and at birth the total kits born and individual
      weights were recorded. Results revealed no gene expression changes in blastocyst
      and endometrial tissue under heatwave exposure. Moreover, our results
      demonstrated that rabbit embryos developed from 8-16 cells to blastocyst during a
      heatwave did not affect implantation rates, total number of kits born and foetal
      losses. In summary, these results demonstrate that heatwave period is not a
      critical point in the reproductive performance of rabbits during blastocyst
      formation.

PMID- 24889110
TI  - Effectiveness of the standard and an alternative set of Streptococcus pneumoniae
      multi locus sequence typing primers.
AB  - BACKGROUND: Multi-locus sequence typing (MLST) is a portable, broadly applicable
      method for classifying bacterial isolates at an intra-species level. This
      methodology provides clinical and scientific investigators with a standardized
      means of monitoring evolution within bacterial populations. MLST uses the DNA
      sequences from a set of genes such that each unique combination of sequences
      defines an isolate's sequence type. In order to reliably determine the sequence
      of a typing gene, matching sequence reads for both strands of the gene must be
      obtained. This study assesses the ability of both the standard, and an
      alternative set of, Streptococcus pneumoniae MLST primers to completely sequence,
      in both directions, the required typing alleles. RESULTS: The results
      demonstrated that for five (aroE, recP, spi, xpt, ddl) of the seven S. pneumoniae
      typing alleles, the standard primers were unable to obtain the complete forward
      and reverse sequences. This is due to the standard primers annealing too closely
      to the target regions, and current sequencing technology failing to sequence the
      bases that are too close to the primer. The alternative primer set described
      here, which includes a combination of primers proposed by the CDC and several
      designed as part of this study, addresses this limitation by annealing to highly
      conserved segments further from the target region. This primer set was
      subsequently employed to sequence type 105 S. pneumoniae isolates collected by
      the Canadian Immunization Monitoring Program ACTive (IMPACT) over a period of 18
      years. CONCLUSIONS: The inability of several of the standard S. pneumoniae MLST
      primers to fully sequence the required region was consistently observed and is
      the result of a shift in sequencing technology occurring after the original
      primers were designed. The results presented here introduce clear documentation
      describing this phenomenon into the literature, and provide additional guidance,
      through the introduction of a widely validated set of alternative primers, to
      research groups seeking to undertake S. pneumoniae MLST based studies.

PMID- 24889111
TI  - Monitoring the dynamics of clonal tumour evolution in vivo using secreted
      luciferases.
AB  - Tumours are heterogeneous cell populations that undergo clonal evolution during
      tumour progression, metastasis and response to therapy. Short hairpin RNAs
      (shRNAs) generate stable loss-of-function phenotypes and are versatile
      experimental tools to explore the contribution of individual genetic alterations
      to clonal evolution. In these experiments tumour cells carrying shRNAs are
      commonly tracked with fluorescent reporters. While this works well for cell
      culture studies and leukaemia mouse models, fluorescent reporters are poorly
      suited for animals with solid tumours--the most common tumour types in cancer
      patients. Here we develop a toolkit that uses secreted luciferases to track the
      fate of two different shRNA-expressing tumour cell clones competitively, both in
      vitro and in vivo. We demonstrate that secreted luciferase activities can be
      measured robustly in the blood stream of tumour-bearing mice to accurately
      quantify, in a minimally invasive manner, the dynamic evolution of two
      genetically distinct tumour subclones in preclinical mouse models of tumour
      development, metastasis and therapy.

PMID- 24889112
TI  - Gendered effects of siblings on child malnutrition in South Asia: cross-sectional
      analysis of demographic and health surveys from Bangladesh, India, and Nepal.
AB  - This study examines the effects of number and sex of siblings on malnutrition of
      boys and girls under-5 in South Asia. Cross-sectional analyses were conducted on
      Demographic and Health Surveys data on children under-5 in Bangladesh (N =
      7,861), India (N = 46,655) and Nepal (N = 2,475). Data were pooled across
      countries, and multinomial logistic regression was used to assess the
      relationship between number and sex of siblings and malnutrition outcomes
      (wasting, stunting, underweight; based on anthropometric data), adjusting for
      country and key social and maternal-child health indicators in sex stratified
      analyses. Number of brothers increased the odds for severe wasting [1 vs. 0
      brothers adjusted odds ratio (AOR) = 1.31, 95 % CI = 1.11, 1.55; 2 vs. 0 brothers
      AOR = 1.36, 95 % CI = 1.07, 1.73] for girls but not boys. Having more male
      siblings and more female siblings increased the odds of stunting for boys and
      girls, but effect of 3+ sisters on severe stunting was significantly stronger for
      girls than boys (girls- 3+ vs. 0 sisters AOR = 2.25, 95 % CI = 1.88, 2.70; boys-
      3+ vs. 0 sisters AOR = 1.37, 95 % CI = 1.13, 1.67). For underweight, three or
      more sisters increased the odds for severe underweight for girls (AOR = 1.27, 95
      % CI = 1.04, 1.57) but not boys. Having brothers heightens girl risk for acute
      malnutrition (wasting), where having multiple sisters increases girl risk for
      chronic malnutrition (stunting/underweight). Boy malnutrition is less affected by
      siblings. Findings suggest that issues of son preference/daughter aversion may
      affect child malnutrition in South Asia.

PMID- 24889113
TI  - Timing of prenatal smoking cessation or reduction and infant birth weight:
      evidence from the United Kingdom Millennium Cohort Study.
AB  - Smoking during pregnancy is a key contributor to poor infant health. Our study
      presents a dynamic relationship between the timing of prenatal smoking cessation
      or reduction and infant birth weight. Using a large representative dataset of a
      birth cohort in the United Kingdom, we apply regression analysis to examine the
      influences of cessation in smoking or reduction in smoking intensity at different
      months or trimesters on infant birth weight. For robustness checks, we use a rich
      set of additional covariates, a series of variable selection procedures,
      alternative birth outcome measures, and stratified samples. We find robust
      evidence that mothers who quit smoking by the third month of pregnancy or the end
      of the first trimester have infants of the same weight as those infants of
      nonsmokers. However, we find smoking cessation in the fourth month or any time
      beyond is associated with substantially lower infant birth weights. Two-thirds of
      the total adverse smoking impact on infant birth weight occurs in the second
      trimester. Our study also shows mothers who smoke throughout pregnancy but cut
      smoking intensity by the third month in pregnancy deliver infants of the same
      weight as those infants born to persistent light smokers. Our research suggests
      the efficacy of prenatal smoking cessation services can be significantly
      improved, if health professionals can encourage more pregnant women to quit
      smoking or reduce smoking intensity timely by the end of the first trimester. 

PMID- 24889114
TI  - Prevalence and risk factors for postpartum depression symptoms among women with
      disabilities.
AB  - The adverse consequences of postpartum depression on the health of the mother and
      her child are well documented. However, there is little information on postpartum
      depression among mothers with disabilities. This study examines the patterns of
      depression and depressive symptoms before, during and after pregnancy and the
      association between depression before and during pregnancy and postpartum
      depression symptomatology (PPD) among women with and without disabilities. Data
      from the 2009-2011 Rhode Island Pregnancy Risk Assessment Monitoring System
      (PRAMS) were analyzed in 2013. Almost 30% (28.9%; 95% CI 22.8-35.8) of mothers
      with disabilities reported often or always feeling down, depressed or sad after
      childbirth compared to 10% of those without disabilities (95% CI 8.9-11.3).
      Compared to other women in the study, women with disabilities had a greater
      likelihood for PPD symptoms (RR 1.6, 95% CI 1.1-2.2) after accounting for
      sociodemographics, maternal characteristics related to PPD, and depression before
      and during pregnancy. Adjusting for other covariates, self-reported prenatal
      diagnosis of depression was not associated with symptoms of PPD and depression
      during pregnancy was marginally associated with PPD symptomatology for women with
      disabilities. Women with disabilities are at a greater risk of experiencing
      symptoms of postpartum depression than other women. Screening for PPD among new
      mothers with disabilities and timely referral of those with PPD diagnosis are
      vital to the health of mothers with disabilities and their children.

PMID- 24889115
TI  - The influence of caregiver depression on children in non-relative foster care
      versus kinship care placements.
AB  - Little is known about how the challenges faced by caregivers influence the
      variation in social, emotional, and behavioral (SEB) outcomes of youth placed in
      kinship versus non-relative foster care. This study examined SEB symptoms among
      youth in kinship and non-relative foster care settings, hypothesizing that
      changes in caregiver depression would modify children's change in behavior over
      time. Child Behavior Checklist (CBCL) assessments of 199 children placed with
      kinship and non-relative foster care providers in a Mid-Atlantic city were
      conducted at time of placement and 6-12 months post-placement. Linear regression
      estimated CBCL change scores for youth across placement type and caregiver
      depression trajectories. Kinship caregivers were more likely to become depressed
      or remained depressed than non-relative foster caregivers. Youth in kinship care
      always exhibited better change in SEB outcomes than youth in non-relative foster
      care, but these positive outcomes were principally observed among families where
      caregivers demonstrated a reduction in depression over time or were never
      depressed. Adjusted change scores for non-relative foster care youth were always
      negative, with the most negative scores among youth whose caregivers became
      depressed over time. Caregiver well-being may modify the influence of placement
      setting on SEB outcomes for youth placed into out-of-home care. Findings lend to
      policy relevance for child welfare systems that seek kinship settings as a
      panacea to the challenges faced by youth, without allocating resources to address
      caregiver needs.

PMID- 24889117
TI  - Revisiting safe sleep recommendations for African-American infants: why current
      counseling is insufficient.
AB  - The American Academy of Pediatrics recommends that children be placed in the
      supine position on firm bedding and not bed share with parents or other children.
      Health professionals increasingly understand that many African-American parents
      do not follow these recommendations, but little research exists on provider
      reactions to this non-compliance. This study was intended to better understand
      how low-income, African-American mothers understand and act upon safe sleep
      recommendations for newborns and how providers counsel these mothers. We
      conducted focus groups with 60 African-American, low-income, first-time mothers
      and telephone interviews with 20 providers serving these populations to explore
      provider counseling and patient decision making. The large majority of mothers
      reported understanding, but not following, the safe-sleeping recommendations. Key
      reasons for non-compliance included perceived safety, convenience, quality of
      infant sleep and conflicting information from family members. Mothers often take
      measures intended to mitigate risk associated with noncompliance, instead
      increasing SIDS risk. Providers recognize that many mothers are non-compliant and
      attribute non-compliance largely to cultural and familial influence. However, few
      provider attempts are made to mitigate SIDS risks from non-compliant behaviors.
      We suggest that counseling strategies should be adapted to: (1) provide greater
      detailed rationale for SIDS prevention recommendations; and (2) incorporate or
      acknowledge familial and cultural preferences. Ignoring the reasons for sleep
      decisions by African-American parents may perpetuate ongoing racial/ethnic
      disparities in SIDS. 

PMID- 24889118
TI  - Organocatalytic enantioselective and (Z)-selective allylation of 3
      indolylmethanol via hydrogen-bond activation.
AB  - An organocatalytic asymmetric allylation of 3-indolylmethanol has been
      established via hydrogen-bond activating mode, which directly assembles isatin
      derived 3-indolylmethanols and o-hydroxystyrenes into chiral allyl-substituted
      oxindoles with one all-carbon quaternary stereogenic center and one newly formed
      C=C bond in excellent enantioselectivity and (Z)-selectivity (up to 97% ee, >20 :
      1 Z/E ratio). This transformation provides an efficient strategy for asymmetric
      C3-functionalization of indoles and allylation of 3-indolylmethanols with precise
      control of the stereoselectivity in the formation of C-C and C=C bonds.

PMID- 24889116
TI  - Prevalence, rates and correlates of intimate partner violence among South African
      women during pregnancy and the postpartum period.
AB  - Intimate partner violence (IPV) is a significant public health problem in South
      Africa. However, limited research exists on IPV during pregnancy and the
      postpartum period in South Africa. The purpose of this study is to describe the
      prevalence, rates and correlates of IPV among South African women during
      pregnancy and the first 9 months postpartum. Data are from a longitudinal study
      with women recruited during pregnancy between 2008 and 2010 at a public clinic in
      Durban. We used a modified version of the World Health Organization's IPV scale
      to estimate prevalence and rates of IPV during pregnancy, at 4 months postpartum
      and 9 months postpartum and we used logistic regression to assess the correlates
      of IPV during this time. More than 20 % of all women experienced at least one act
      of physical, psychological or sexual IPV during pregnancy. Nearly one-quarter of
      all women experienced at least one act of physical, psychological or sexual IPV
      during the first 9 months postpartum. Psychological IPV was the most prevalent
      type of IPV during pregnancy and the first 4 months postpartum. Age and previous
      violence within the relationship were associated with IPV during pregnancy and
      IPV during the postpartum period. The high levels of IPV during pregnancy and the
      postpartum period highlight the need to develop screening and intervention
      strategies specifically for this time. Further, women should be screened not only
      for physical violence but also psychological violence given that psychological
      violence may result in distinct negative consequences.

PMID- 24889119
TI  - How meaning similarity influences ambiguous word processing: the current state of
      the literature.
AB  - The majority of words in the English language do not correspond to a single
      meaning, but rather correspond to two or more unrelated meanings (i.e., are
      homonyms) or multiple related senses (i.e., are polysemes). It has been proposed
      that the different types of "semantically-ambiguous words" (i.e., words with more
      than one meaning) are processed and represented differently in the human mind.
      Several review papers and books have been written on the subject of semantic
      ambiguity (e.g., Adriaens, Small, Cottrell, & Tanenhaus, 1988; Burgess & Simpson,
      1988; Degani & Tokowicz, 2010; Gorfein, 1989, 2001; Simpson, 1984). However,
      several more recent studies (e.g., Klein & Murphy, 2001; Klepousniotou, 2002;
      Klepousniotou & Baum, 2007; Rodd, Gaskell, & Marslen-Wilson, 2002) have
      investigated the role of the semantic similarity between the multiple meanings of
      ambiguous words on processing and representation, whereas this was not the
      emphasis of previous reviews of the literature. In this review, we focus on the
      current state of the semantic ambiguity literature that examines how different
      types of ambiguous words influence processing and representation. We analyze the
      consistent and inconsistent findings reported in the literature and how factors
      such as semantic similarity, meaning/sense frequency, task, timing, and modality
      affect ambiguous word processing. We discuss the findings with respect to recent
      parallel distributed processing (PDP) models of ambiguity processing (Armstrong &
      Plaut, 2008, 2011; Rodd, Gaskell, & Marslen-Wilson, 2004). Finally, we discuss
      how experience/instance-based models (e.g., Hintzman, 1986; Reichle & Perfetti,
      2003) can inform a comprehensive understanding of semantic ambiguity resolution. 

PMID- 24889120
TI  - The SF1 helicase encoded by the archaeal plasmid pTN2 of Thermococcus nautili.
AB  - We expressed, purified, and characterized the helicase encoded by ORF1 of the
      Thermococcus nautili pTN2 plasmid (Soler et al. Nucl Acids Res 38, 5088-5104,
      2010). The enzyme, which belongs to the SF1 family of helicases, possesses NTPase
      activity, with a strong preference for ATP and GTP as compared to CTP and TTP;
      dATP was also a substrate. Triphosphatase activity was strongly stimulated by
      single-stranded DNA and, to a lesser extent, by double-stranded DNA. Unwinding of
      duplexes comprising a fluorescent oligonucleotide was monitored by fluorescence
      polarization spectroscopy and by polyacrylamide gel electrophoresis. As observed
      for enzymes of the same family, pTN2 helicase displays a strong preference for
      duplexes comprising a 3' single-stranded extension and proceeds from the 3' to
      the 5' end of the loading strand. Under the conditions of the in vitro assay,
      pTN2 helicase did not appear to be recycled, but stayed bound to single-stranded
      DNA, which explains why high concentrations of enzyme are required to unwind long
      stretches of duplex DNA. The helicase enhances the synthesis of double-stranded
      DNA by pTN2 primase and by T. nautili PolB polymerase primed by pTN2 primase but
      it did not enhance synthesis by Taq DNA polymerase. 

PMID- 24889121
TI  - The preoperative neutrophil-lymphocyte ratio predicts recurrence and survival
      among patients undergoing R0 resections of adenocarcinomas of the esophagogastric
      junction.
AB  - BACKGROUND AND OBJECTIVES: Elevated preoperative neutrophil-lymphocyte ratio
      (NLR) and platelet-lymphocyte ratio (PLR) predict survival rates among patients
      with several types of cancer. The current study sought to clarify whether NLR and
      PLR are clinically useful independent prognostic indicators of adenocarcinomas of
      the esophagogastric junction (AEG) among patients undergoing curative resections
      (i.e., R0 resections). METHODS: A total of 327 patients who underwent R0
      resections for AEG were enrolled in the study. Data concerning demographic
      parameters, laboratory analyses, histopathology, and survival time were collected
      and analyzed. RESULTS: A total of 123 patients (37.6%) had elevated preoperative
      NLR (>= 5). The median follow-up duration was 24.7 months (range = 2-39 months).
      NLR was significantly related to histology (P = 0.035), pTNM stage (P < 0.0001)
      and tumor recurrence (P = 0.022). Univariate analyses revealed that NLR were
      significantly associated with disease-free survival (DFS) and overall survival
      (OS; both P < 0.0001). Multivariable analyses revealed that elevated NLR
      independently predicted poorer DFS (hazard ratio [HR] = 2.551, P < 0.0001) and OS
      (HR = 2.743, P < 0.0001). However, PLR did not significantly predict DFS or OS.
      CONCLUSION: The present study indicates that elevated preoperative NLR (>= 5) is
      a useful marker of tumor recurrence and independently predicts poorer disease
      free and overall survival among patients with AEG undergoing R0 resections.

PMID- 24889122
TI  - General catalytic methylation of amines with formic acid under mild reaction
      conditions.
AB  - A general catalytic protocol for the methylation of amines has been developed
      applying, for the first time, formic acid as the C1 building block and silanes as
      reducing agents. A broad range of aromatic and aliphatic, both primary and
      secondary, amines has been converted to the corresponding tertiary amines
      including [N-(13)C]-labelled drugs in good to excellent yields under mild
      conditions.

PMID- 24889123
TI  - Senescence of bone marrow mesenchymal stromal cells is accompanied by activation
      of p53/p21 pathway in myelodysplastic syndromes.
AB  - The contribution of bone marrow mesenchymal stromal cells (BMMSCs) to the
      pathogenesis of myelodysplastic syndrome (MDS) has created controversies. In this
      study, we confirmed that BMMSCs from MDS patients showed prominent features of
      senescence, which were characterized by increased cell size, decreased
      proliferation and colony-forming potential, alteration of cytoskeleton, and
      increased senescence-associated beta-galactosidase (SA-beta-Gal) activity.
      Interestingly, the apoptosis assay results showed that the percentage of
      apoptosis cells was very low and the difference was not significant between MDS
      patients and normal controls. Moreover, the osteogenic differentiation potential
      of BMMSCs from lower risk but not higher risk MDS was impaired, indicated by
      cytochemical stainings and reduced expressions of RUNX2. In addition, BMMSCs from
      MDS patients had impaired hematopoietic supporting function. Furthermore, the
      expression of p53 and p21 which played an important role in regulating the
      senescence progress of BMMSCs was significantly increased, whereas levels of p16
      and pRb expression were not changed in the BMMSCs from MDS patients. Taken
      together, our comprehensive analysis shows that BMMSCs from MDS patients
      exhibited senescent behavior and activation of p53/p21 pathway probably played an
      important role in the senescence process.

PMID- 24889124
TI  - Umbilical stoma as a diverting loop ileostomy in laparoscopic colorectal surgery.

PMID- 24889125
TI  - Impact of Bacillus amyloliquefaciens S13-3 on control of bacterial wilt and
      powdery mildew in tomato.
AB  - BACKGROUND: Biological control is a non-hazardous technique to control plant
      diseases. Researchers have explored microorganisms that show high plant-disease
      control efficiency for use as biological control agents. RESULTS: A single soil
      application of Bacillus amyloliquefaciens strain S13-3 suppressed tomato
      bacterial wilt caused by Ralstonia solanacearum, a soilborne bacterial pathogen,
      through production of antibiotics augmented possibly by induction of systemic
      acquired resistance. Soil application also controlled tomato powdery mildew
      disease through induction of systemic acquired resistance. CONCLUSION: S13-3
      showing bifunctional activity with a single application to soil may be an
      innovative biological control agent against bacterial wilt and powdery mildew in
      tomato.

PMID- 24889126
TI  - Right ventricular (18)F-FDG uptake is an important indicator for cardiac
      involvement in patients with suspected cardiac sarcoidosis.
AB  - PURPOSE: Cardiac sarcoidosis is most commonly found in the left ventricular (LV)
      free wall. Presence in the right ventricle (RV) is less common but might be
      useful for detecting cardiac involvement of sarcoidosis. (18)F-fluorodeoxyglucose
      ((18)F-FDG) PET has been used to detect LV regions with cardiac sarcoidosis.
      However, the same has not been done for RV involvement. The aims of the current
      study were to evaluate RV (18)F-FDG uptake and its relationship to the
      distribution of LV wall (18)F-FDG-positive segments in the LV, and to evaluate
      whether patients with positive RV (18)F-FDG uptake met the 1993 diagnostic
      criteria of the Japanese Ministry of Health and Welfare (JMHW) guidelines
      regarding sarcoidosis with suspected cardiac involvement. METHOD: Fifty-nine
      biopsy-proven extra-cardiac sarcoidosis patients (age 56.1 +/- 14.7 years) with
      suspected cardiac involvement based on abnormal electrocardiography or
      echocardiography findings underwent fasting (18)F-FDG PET or PET/CT. The LV wall
      was divided into 17 segments and RV uptake was also evaluated. RESULT: Among 59
      patients, 35 (59.3%) showed some abnormal (18)F-FDG uptake in the RV and/or LV
      wall. With respect to the RV wall, 13 (22.0%) showed abnormal (18)F-FDG uptake.
      The number of LV-involved segments was 4.8 +/- 2.4 in the patients with RV (18)F
      FDG uptake, which was significantly higher than in the patients without RV
      uptake, 1.8 +/- 2.2 (P < 0.0001). Patients with RV uptake more frequently met the
      diagnostic criteria of the 1993 JMHW guidelines (n = 27), than did those without
      RV uptake (84.6 vs. 34.8%, P = 0.0033). CONCLUSION: (18)F-FDG PET identified RV
      involvement less frequently than LV involvement in this study population.
      However, patients who had RV uptake showed a greater number of LV-involved
      segments and met the JMHW diagnostic criteria more frequently. Although RV uptake
      is less frequent, (18)F-FDG RV uptake may be useful in diagnosing cardiac
      involvement in sarcoidosis. CLINICAL TRIAL REGISTRATION: UMIN000006533.

PMID- 24889127
TI  - Usefulness of (99m)Tc-pertechnetate whole body scan with neck and chest SPECT/CT
      for detection of post-surgical thyroid remnant and metastasis in differentiated
      thyroid cancer patients.
AB  - OBJECTIVE: The aim of the study was to evaluate the usefulness of (99m)Tc
      pertechnetate whole body scan (WBS) with neck and chest SPECT/CT for detection of
      post-surgical thyroid remnant and metastasis in differentiated thyroid cancer
      (DTC) patients. METHODS: Fifty-six post total thyroidectomy patients were
      included. All patients were prospectively imaged with (99m)Tc-pertechnetate WBS
      with neck and chest SPECT/CT before (131)I ablation. The post-ablative (131)I WBS
      with SPECT/CT was performed at 5-7 days after receiving (131)I. Both scans were
      directly compared to determine the concordance of sites and number of remnant and
      metastasis. RESULTS: Overall per-patient analysis, the percentage of concordance
      between two scans was 96.4%. In thyroid bed, lymph node, lung and bone subgroups,
      the percentage of concordance between two scans was 96.4, 92.9, 98.2 and 100%,
      respectively. All of them show good correlation with unweighted kappa between 0.7
      and 1. Overall per-lesion analysis, the percentage of concordance between two
      scans was 84%. In thyroid bed, lymph node, lung and bone subgroups, the
      percentage of concordance between two scans was 89.5, 55, 82.6 and 50%,
      respectively. CONCLUSIONS: Pre-ablative pertechnetate WBS with neck and chest
      SPECT/CT has good correlation for the detection of post-surgical thyroid remnant,
      cervical node and discrete lung nodule metastasis as compared to (131)I WBS with
      SPECT/CT per-patient basis. Because (131)I therapeutic activity is desired base
      on metastatic site and less concerning about the number of lesions, pre-ablative
      (99m)Tc-pertechnetate WBS with SPECT/CT was a good alternative tool to avoid
      radioiodine stunning in post-surgical DTC patients.

PMID- 24889128
TI  - Novel isoforms of the bovine Nuclear factor I/X (CCAAT-binding transcription
      factor) transcript products and their diverse expression profiles.
AB  - The aim of this study was to detect splicing variants of the bovine NFIX gene and
      determine their expression regulations. Through bioinformatics analysis, we
      predicted five isoforms of the bovine NFIX transcript product and validated their
      existence using cDNA pool and sequencing methods. The five isoforms had a common
      5'-terminal sequence and various 3'-terminal sequences. Nuclear factor I family
      genes can activate or repress transcription by a highly variable C-terminal
      region. Thus, the five isoform products from a single gene may function
      differently. Quantitative PCR results showed that NFIX had highest expression in
      brain; medial expression in lung and muscle; and lower expression in spleen,
      kidney, liver and heart of both embryo and adult cattle. However, the expression
      levels NFIX in adult tissues were significantly decreased, and the diversity of
      its alternative splicing events was lower. Each isoform was expressed differently
      in different tissues at the embryo and adult stages. One of the isoforms (Nfix2)
      was not detected in tissues of adult cattle. In brain, another of the isoforms
      (Nfix3) was not detected, whereas the other four isoforms were highly expressed.
      In the embryo, of the five isoforms, the profile of the one labeled Nfix4 was the
      most similar to that of total Nfix, and we proved that it was the major isoform.
      This study is the first that has detected five novel isoforms of the bovine NFIX
      transcript products and that has examined their profiles at spatial and temporal
      levels, which will provide essential information for better understanding the
      bovine NFIX gene. 

PMID- 24889129
TI  - Topical application of the adenosine A2A receptor agonist CGS-21680 prevents
      phorbol-induced epidermal hyperplasia and inflammation in mice.
AB  - The nucleoside adenosine is a known regulator of immunity and inflammation that
      mediates, at least in part, the anti-inflammatory effect of methotrexate, an
      immunosuppressive agent widely used to treat autoimmune inflammatory diseases.
      Adenosine A2A receptors play a key role in the inhibition of the inflammatory
      process besides promoting wound healing. Therefore, we aimed to determine the
      topical effect of a selective agonist, CGS-21680, on a murine model of skin
      hyperplasia with a marked inflammatory component. Pretreatment with either CGS
      21680 (5 MUg per site) or the reference agent dexamethasone (200 MUg/site)
      prevented the epidermal hyperplasia and inflammatory response induced by topical
      application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 nmol/site) for three
      consecutive days. The histological analysis showed that both CGS-21680 and
      dexamethasone produced a marked reduction of inflammatory cell infiltrate, which
      correlated with diminished myeloperoxidase (MPO) activity in skin homogenates.
      Both treatments reduced the levels of the chemotactic mediators LTB4 and CXCL-1,
      and the inflammatory cytokine TNF-alpha, through the suppression of NFkappaB
      phosphorylation. The immunohistochemical analysis of the hyperproliferative
      markers cytokeratin 6 (CK6) and Ki67 revealed that while both agents inhibit the
      number of proliferating cells in the epidermis, CGS-21680 treatment promoted
      dermal fibroblasts proliferation. Consistently, increased collagen deposition in
      dermis was observed in tissue sections from agonist-treated mice. Our results
      showed that CGS 21680 efficiently prevents phorbol-induced epidermal hyperplasia
      and inflammation in mice without the deleterious atrophic effect of topical
      corticosteroids. 

PMID- 24889130
TI  - Lesion-specific differences for implantable cardioverter defibrillator therapies
      in adults with congenital heart disease.
AB  - BACKGROUND: Sudden cardiac death is a major cause of late mortality in adults
      with congenital heart disease (ACHD). While data exist for adults with repaired
      Tetralogy of Fallot (TOF), little is known about those with non-TOF lesions. We
      examined the relative rates in implantable cardioverter defibrillator (ICD)
      therapy according to congenital lesion type in a large-volume adult congenital
      heart center. METHODS: A cohort of 59 individuals (median follow up time, 3.2
      years range 0-10) with ACHD and ICDs was stratified according to underlying
      congenital lesion and implant indication. Appropriate therapies were defined as
      any therapy for a physician-adjudicated ventricular arrhythmia. Rates of
      inappropriate and appropriate ICD therapies were analyzed according to several
      relevant clinical variables. RESULTS: Thirty-three (56%) TOF, 15 (25.4%) L- or D
      transposition of great arteries, and 11 (18.6%) with other lesions were included
      in the analysis. Approximately half (52.5%) were implanted for primary prevention
      indications. During follow-up, 12 (20.3%) patients received appropriate ICD
      therapies and 13 (22%) patients received inappropriate therapies. The incidence
      of appropriate shocks among patients with TOF was 27.3% (9/33) compared to 11.5%
      (3/26) among non-TOF diagnoses during the follow-up time (p = 0.043).
      CONCLUSIONS: ACHD patients with non-TOF congenital lesions are significantly less
      likely to receive appropriate ICD therapy than those with TOF. Our analysis calls
      into question the validity of traditional ICD implantation guidelines in this
      growing and diverse patient population.

PMID- 24889131
TI  - Acceleration and selective monomer addition during aqueous RAFT copolymerization
      of ionic monomers at 25  degrees C.
AB  - An acceleration effect and selective monomer addition during RAFT
      copolymerization of the oppositely-charged ionic monomers in dilute aqueous
      solution at 25  degrees C are reported. The reaction is conducted using a non
      ionic water-soluble polymer as a macromolecular chain transfer agent under
      visible light irradiation. A fast iterative polymerization can be induced, even
      in dilute solution, by the favorable ionic interactions and in situ self-assembly
      of zwitterionic growing chains. Selelctive monomer addition is achieved in the
      statistical copolymerization due to the ion-pairing of the oppositely-charged
      monomers, such as precisely the same reaction rates at a 1:1 of monomer ratio,
      otherwise a faster reaction of the minor monomer component over the major one.
      These behaviors open up an avenue towards the rapid synthesis of sequence
      controlled zwitterionic polyelectrolytes that can satisfy the demands of emerging
      biological applications. 

PMID- 24889132
TI  - Rapidly developing and self-limiting eosinophilia associated with clozapine.

PMID- 24889133
TI  - Seasonal invasion dynamics in a spatially heterogeneous river with fluctuating
      flows.
AB  - A key problem in environmental flow assessment is the explicit linking of the
      flow regime with ecological dynamics. We present a hybrid modeling approach to
      couple hydrodynamic and biological processes, focusing on the combined impact of
      spatial heterogeneity and temporal variability on population dynamics. Studying
      periodically alternating pool-riffle rivers that are subjected to seasonally
      varying flows, we obtain an invasion ratchet mechanism. We analyze the ratchet
      process for a caricature model and a hybrid physical-biological model. The water
      depth and current are derived from a hydrodynamic equation for variable stream
      bed water flows and these quantities feed into a reaction-diffusion-advection
      model that governs population dynamics of a river species. We establish the
      existence of spreading speeds and the invasion ratchet phenomenon, using a
      mixture of mathematical approximations and numerical computations. Finally, we
      illustrate the invasion ratchet phenomenon in a spatially two-dimensional
      hydraulic simulation model of a meandering river structure. Our hybrid modeling
      approach strengthens the ecological component of stream hydraulics and allows us
      to gain a mechanistic understanding as to how flow patterns affect population
      survival. 

PMID- 24889134
TI  - Topical delivery of fluorescence (6-Cf) labeled and radiolabeled (99m-Tc)
      cisplatin and imiquimod by a dual drug delivery system.
AB  - The present investigation deals with the development of topical (top.)
      formulation for co-delivery of cisplatin and imiquimod to enhance the antitumor
      efficacy of the drug for skin-cited malignancies even in immune compromised
      patient. Cisplatin (CDDP) and imiquimod-loaded protransfersome gel (CDDP-Imi-Pts
      gel) formulation was characterized for entrapment efficiency, pH, and viscosity.
      Further, fluorescence-labeled (6-carboxyfluorescin) and radiolabeled ((99m)
      technetium) drug-loaded formulations were compared with respect to
      biodistribution and pharmacokinetic studies. Gamma scintigraphy of mice following
      radiolabeled formulation administrations was performed to accomplish the
      localization of drugs in various organs. The percentage entrapment efficiency of
      cisplatin and imiquimod in the protransfersome gel formulations were found to be
      36.22 +/- 6.41 and 63.11 +/- 3.73. The skin/blood localization ratio of 1.096,
      120.13, 0.174, and 349.88 was found for intraperitoneal radiolabeled drug
      solution ((99m-)Tc-CDDP-Imi-Sol), top. radiolabeled drug-loaded protransfersome
      gel formulation ((99m-)Tc-CDDP-Imi-Pts gel), intraperitoneal 6-carboxyfluorescin
      labeled drug solution (6-Cf-CDDP-Imi-Sol), top. 6-carboxyfluorescin labeled drug
      loaded protransfersome gel formulation (6-Cf-CDDP-Imi-Pts gel), respectively
      after 0.5h of administration. CDDP-Imi-Pts gel has a potential for site specific
      delivery and reduces the systemic toxicity of anti cancer drugs. These findings
      suggest that the cisplatin-imiquimod co-delivery offers an attractive, novel
      approach for treatment of skin-cited malignancies.

PMID- 24889135
TI  - Catalytic hetero-ene reactions of 5-methyleneoxazolines: highly enantioselective
      synthesis of 2,5-disubstituted oxazole derivatives.
AB  - An efficient catalytic asymmetric hetero-ene reaction of 5-methyleneoxazolines
      with 1,2-dicarbonyl compounds (including alpha-ketoesters and glyoxal
      derivatives) was realized using Ni(II)-N,N'-dioxide complexes as the catalysts.
      It provides a rapid, high yielding (up to 99%) route for the preparation of 2,5
      disubstituted oxazole derivatives in a highly enantioenriched form (up to >99%
      ee) under mild conditions.

PMID- 24889136
TI  - The Children's Oncology Group Childhood Cancer Research Network (CCRN): case
      catchment in the United States.
AB  - BACKGROUND: The Childhood Cancer Research Network (CCRN) was established within
      the Children's Oncology Group (COG) in July 2008 to provide a centralized
      pediatric cancer research registry for investigators conducting approved
      etiologic and survivorship studies. The authors conducted an ecological analysis
      to characterize CCRN catchment at >200 COG institutions by demographic
      characteristics, diagnosis, and geographic location to determine whether the CCRN
      can serve as a population-based registry for childhood cancer. METHODS: During
      2009 to 2011, 18,580 US children newly diagnosed with cancer were registered in
      the CCRN. These observed cases were compared with age-specific, sex-specific, and
      race/ethnicity-specific expected numbers calculated from Surveillance,
      Epidemiology, and End Results (SEER) Program cancer incidence rates and 2010 US
      Census data. RESULTS: Overall, 42% of children (18,580 observed/44,267 expected)
      who were diagnosed with cancer at age <20 years were registered in the CCRN,
      including 45%, 57%, 51%, 44%, and 24% of those diagnosed at birth, ages 1 to 4
      years, ages 5 to 9 years, ages 10 to 14 years, and ages 15 to 19 years,
      respectively. Some malignancies were better represented in the CCRN (leukemia,
      59%; renal tumors, 67%) than others (retinoblastoma, 34%). There was little
      evidence of differences by sex or race/ethnicity, although rates in nonwhites
      were somewhat lower than rates in whites. CONCLUSIONS: Given the low observed-to
      expected ratio, it will be important to identify challenges and barriers to
      registration to improve case ascertainment, especially for rarer diagnoses and
      older age groups; however, it is encouraging that some diagnoses in younger
      children are fairly representative of the population. Overall, the CCRN is
      providing centralized, real-time access to cases for research and could be used
      as a model for other national cooperative groups.

PMID- 24889137
TI  - Effects of black tea on body composition and metabolic outcomes related to
      cardiovascular disease risk: a randomized controlled trial.
AB  - There is increasing evidence that tea and its non-caffeine components (primarily
      flavonoids) contribute to cardiovascular health. Randomized controlled trials
      have shown that tea can improve cardiovascular disease risk factors. We have
      previously reported a non-caffeine associated beneficial effect of regular black
      tea consumption on blood pressure and its variation. OBJECTIVE: To explore the
      non-caffeine associated effects of black tea on body weight and body fat
      distribution, and cardiovascular disease related metabolic outcomes. DESIGN:
      regular tea-drinking men and women (n = 111; BMI 20-35 kg m(-2)) were recruited
      to a randomized controlled double-blind 6 month parallel-designed trial.
      Participants consumed 3 cups per day of either powdered black tea solids (tea) or
      a flavonoid-free flavour- and caffeine-matched placebo (control). Body weight,
      waist- and hip-circumference, endothelial function and plasma biomarkers were
      assessed at baseline, 3 months and 6 months. RESULTS: Compared to control,
      regular ingestion of black tea over 3 months inhibited weight gain (-0.64 kg, p =
      0.047) and reduced waist circumference (-1.88 cm, P = 0.035) and waist-to-hip
      ratio (-0.03, P = 0.005). These effects were no longer significant at 6 months.
      There were no significant effects observed on fasting glucose, insulin, plasma
      lipids or endothelial function. CONCLUSION: Our study suggests that short-term
      regular ingestion of black tea over 3 months can improve body weight and body fat
      distribution, compared to a caffeine-matched control beverage. However, there was
      no evidence that these effects were sustained beyond 3 months.

PMID- 24889139
TI  - In silico concurrent multisite pH titration in proteins.
AB  - The concurrent proton binding at multiple sites in macromolecules such as
      proteins and nucleic acids is an important yet challenging problem in
      biochemistry. We develop an efficient generalized Hamiltonian approach to attack
      this issue. Based on the previously developed generalized-ensemble methods, an
      effective potential energy is constructed which combines the contributions of all
      (relevant) protonation states of the molecule. The effective potential preserves
      important phase regions of all states and, thus, allows efficient sampling of
      these regions in one simulation. The need for intermediate states in alchemical
      free energy simulations is greatly reduced. Free energy differences between
      different protonation states can be determined accurately and enable one to
      construct the grand canonical partition function. Therefore, the complicated
      concurrent multisite proton titration process of protein molecules can be
      satisfactorily simulated. Application of this method to the simulation of the pKa
      of Glu49, Asp50, and C-terminus of bovine pancreatic trypsin inhibitor shows
      reasonably good agreement with published experimental work. This method provides
      an unprecedented vivid picture of how different protonation states change their
      relative population upon pH titration. We believe that the method will be very
      useful in deciphering the molecular mechanism of pH-dependent biomolecular
      processes in terms of a detailed atomistic description.

PMID- 24889140
TI  - Control of the particle distribution in inkjet printing through an evaporation
      driven sol-gel transition.
AB  - A ring stain is often an undesirable consequence of droplet drying. Particles
      inside evaporating droplets with a pinned contact line are transported toward the
      periphery by radial flow. In this paper, we demonstrate how suspensions of
      laponite can be used to control the radial flow inside picoliter droplets and
      produce uniform deposits. The improvement in homogeneity arises from a sol-gel
      transition during evaporation. Droplets gel from the contact line inward,
      reducing the radial motion of particles and thus inhibiting the formation of a
      ring stain. The internal flows and propagation of the gelling front were followed
      by high-speed imaging of tracer particles during evaporation of the picoliter
      droplets of water. In the inkjet nozzle, the laponite network is broken down
      under high shear. Recovery of the low shear viscosity of laponite suspensions was
      shown to be fast with respect to the lifetime of the droplet, which was
      instrumental in controlling the deposit morphology. The radial and vertical
      particle distributions within dried deposits were measured for water droplets
      loaded with 1 and 5 wt % polystyrene spheres and various concentrations of
      laponite. Aggregation of the polystyrene spheres was suppressed by the addition
      of colloidal silica. The formulation can be tuned to vary the deposit profile
      from a ring to a pancake or a dome. 

PMID- 24889138
TI  - Prospective, randomized, single blinded pilot study of a new FlatWire based
      sternal closure system.
AB  - BACKGROUND: Unstable steel wire cerclage following open heart surgery may result
      in increased pain, sternal cut-through, non-union, or dehiscence. These
      complications lead to longer hospital stays, increased cost, higher morbidity,
      and patient dissatisfaction. The Figure 8 FlatWire Sternal Closure System is a
      new construct which is a simple, intuitive, and inexpensive alternative for
      primary sternal repair following open heart surgery. Prior bench-top testing of
      FlatWire has demonstrated superior strength and stiffness compared to traditional
      steel wire. We present our initial experience in a prospective, randomized,
      single blinded pilot study utilizing this FDA approved system. METHODS: Sixty
      three patients undergoing elective complete sternotomies at a single institution
      were randomly assigned to receive either the Figure 8 FlatWire or standard steel
      wire cerclage. All surgeries were performed by a single board certified
      cardiothoracic surgeon. Data collected included: Age, BMI, pump time, off pump to
      surgical stop time, length of hospital stay after surgery, cost from time of
      surgery to discharge, and pain on a visual analog pain scale on the day of
      discharge, day 30, and day 60. RESULTS: The groups were well matched. Patients
      receiving the Figure 8 FlatWire (33) had a reduction in length of stay compared
      to patients receiving steel wire circlage (30), but it was not statistically
      significant (6.8 vs. 7.8 days respectively, p < 0.093). Additionally those with
      the FlatWire reported significantly decreased pain at day of discharge (3.07 vs.
      4.92 points on pain scale, p < 0.0066), with similar pain scores at 30 and 60
      days. Off pump to surgery stop time was increased by 15.9 minutes in patients
      receiving the FlatWire vs. steel wires (55.7 vs. 71.6 minutes, p = 0.00025). Mean
      cost from surgery until discharge was $87,820.98 in the FlatWire group vs.
      $91,930.29 in the steel wire group (p < 0.3082). CONCLUSION: Early clinical
      results suggest that Figure 8 FlatWire provides excellent stability, which
      resulted in significantly diminished postoperative pain at discharge. Although
      not significant there was a trend toward decreased length of stay, and reduced
      cost. Further clinical research is warranted to expand upon these initial trends
      and validate long term outcomes.

PMID- 24889141
TI  - The association between perceived and observed ability to use everyday technology
      in people of working age with ABI.
AB  - OBJECTIVE: Everyday technology (ET), including computers and automated telephone
      services, is increasingly required for everyday functioning. However, people with
      acquired brain injury (ABI) may have difficulty with ET use. To design
      interventions to support ET use, further knowledge of how to assess dimensions of
      such use is needed. METHODS: This study investigated the relationship between the
      perceived difficulty of ET use (self-reported using the short version of the
      Everyday Technology Use Questionnaire, S-ETUQ) and observed ability to use ET
      (observed using the Management of Everyday Technology Assessment, META) in a
      sample of people with ABI (n = 81). Data were analysed using a Rasch measurement
      model, and person measures of perceived difficulty and observed ability to use ET
      were identified and correlated. Results and conclusions. The person measures had
      a correlation of 0.49 (p < 0.001). In groups of different severity levels after
      ABI, significant associations were found in the moderate (0.36) and severe (0.47)
      disability groups. In the good recovery group, only a non-significant correlation
      was found (0.21). This indicates that the S-ETUQ and the META measure different
      but complementary dimensions of ET use. Hence, the assessments are proposed to be
      used together in clinical practice to more fully understand the ability of people
      with ABI to use ET.

PMID- 24889142
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health.

PMID- 24889143
TI  - A systematic review and meta-analysis of experimental clinical evidence on
      initial aligning archwires and archwire sequences.
AB  - The aim of the study was to assess treatment effects and potential side effects
      of different archwires used on patients receiving orthodontic therapy. Electronic
      and manual unrestricted searches were conducted in 19 databases including
      MEDLINE, Cochrane Library, and Google Scholar until April 2012 to identify
      randomized controlled trials (RCTs) and quasi-RCTs. After duplicate study
      selection, data extraction, risk of bias assessment with the Cochrane risk of
      bias tool, and narrative analysis, mean differences (MDs) with confidence
      intervals (CIs) of similar studies were pooled using a random-effects model and
      evaluated with GRADE. A total of 16 RCTs were included assessing different
      archwire characteristics on 1108 patients. Regarding initial archwires, meta
      analysis of two trials found slightly greater irregularity correction with an
      austenitic-active nickel-titanium (NiTi) compared with an martensitic-stabilized
      NiTi archwire (corresponding to MD: 1.11 mm, 95% CI: -0.38 to 2.61). Regarding
      archwire sequences, meta-analysis of two trials found it took patient treated
      with a sequence of martensitic-active copper-nickel-titanium (CuNiTi) slightly
      longer to reach the working archwire (MD: 0.54 months, 95% CI: -0.87 to 1.95)
      compared with a martensitic-stabilized NiTi sequence. However, patients treated
      with a sequence of martensitic-active CuNiTi archwires reported general greater
      pain intensity on the Likert scale 4 h and 1 day after placement of each
      archwire, compared with a martensitic-stabilized NiTi sequence. Although
      confidence in effect estimates ranged from moderate to high, meta-analyses could
      be performed only for limited comparisons, while inconsistency might pose a
      threat to some of them. At this point, there is insufficient data to make
      recommendations about the majority of initial archwires or for a specific
      archwire sequence.

PMID- 24889144
TI  - JNK1/2-dependent phosphorylation of angulin-1/LSR is required for the exclusive
      localization of angulin-1/LSR and tricellulin at tricellular contacts in EpH4
      epithelial sheet.
AB  - Tricellular tight junctions (tTJs) are specialized structural variants of tight
      junctions within tricellular contacts of an epithelial sheet and comprise several
      transmembrane proteins including lipolysis-stimulated lipoprotein receptor
      (angulin-1/LSR) and tricellulin. To elucidate the mechanism of its formation, we
      carried out stepwise screening of kinase inhibitors followed by RNAi screening to
      identify kinases that regulate intracellular localization of angulin-1/LSR to the
      tTJs using a fluorescence image-based screen. We found that the activity of JNK1
      and JNK2, but not JNK3, was required for the exclusive localization of angulin
      1/LSR at the tTJs. Based on a bioinformatics approach, we estimated the potential
      phosphorylation site of angulin-1/LSR by JNK1 to be serine 288 and experimentally
      confirmed that JNK1 directly phosphorylates angulin-1/LSR at this site. We found
      that JNK2 was also involved in the phosphorylation of angulin-1/LSR. Furthermore,
      GFP-tagged angulin-1/LSR(S288A), in which serine 288 was substituted by alanine,
      was observed to be dispersed to bicellular junctions, indicating that
      phosphorylation of Ser288 is crucial for the exclusive localization of angulin
      1/LSR and tricellulin at tTJs. Our fluorescence image-based screening for kinases
      inhibitor or siRNAs combined with the phosphorylation site prediction could
      become a versatile and useful tool to elucidate the mechanisms underlying the
      maintenance of tTJs regulated by kinase networks. 

PMID- 24889145
TI  - Sample size/power calculation for stratified case-cohort design.
AB  - The case-cohort (CC) study design usually has been used for risk factor
      assessment in epidemiologic studies or disease prevention trials for rare
      diseases. The sample size/power calculation for a stratified CC (SCC) design has
      not been addressed before. This article derives such result based on a stratified
      test statistic. Simulation studies show that the proposed test for the SCC design
      utilizing small sub-cohort sampling fractions is valid and efficient for
      situations where the disease rate is low. Furthermore, optimization of sampling
      in the SCC design is discussed and compared with proportional and balanced
      sampling techniques. An epidemiological study is provided to illustrate the
      sample size calculation under the SCC design.

PMID- 24889146
TI  - Epidemiology and outcomes in refractive lens exchange surgery.
AB  - PURPOSE: To assess demographics and refractive outcomes in patients undergoing
      refractive lens exchange surgery (RLE), with a population of cataract patients as
      a reference. METHODS: A RLE cohort from a private eye clinic (n = 675) and a
      cataract cohort from the outcome registration of the Swedish National Cataract
      Register were studied and compared from an epidemiological perspective regarding
      age, gender, preoperative refraction and postoperative refractive outcome.
      RESULTS: The RLE patients were younger (52.1 +/- 7.7 versus 73.84 +/- 9.32 years)
      with a smaller percentage of women (45.28% versus 60.46%; p < 0.001) and were
      more often myopic than the cataract patients. Astigmatism and hyperopia did not
      differ between the cohorts. Uncorrected visual acuity after RLE equalled the best
      corrected visual acuity in best cases after cataract surgery. The absolute
      biometry prediction was more accurate in RLE (0.17 +/- 0.27 D versus 0.40 +/-
      0.58 D; p < 0.001), particularly in patients given a customized toric IOL (0.12
      +/- 0.27 D; p < 0.05). In cataracts, the Haigis' formula showed higher accuracy
      than the SRK/T formula (0.39 +/- 0.53 D versus 0.43 +/- 0.61 D; p < 0.01).
      Postoperatively after RLE, Laser Epithelial Keratomileusis was performed in 9.04%
      and Yttrium Aluminium Garnet capsulotomy in 7.41% of the eyes. Other reoperations
      were performed in three cases, and five postoperative retinal detachments
      occurred after RLE. CONCLUSION: Compared with patients undergoing cataract
      surgery, we see many similarities, but also many interesting differences in
      patients undergoing RLE. Basic information about the growing population choosing
      to undergo RLE can help us plan future ophthalmic care.

PMID- 24889150
TI  - Monitoring nocturnal heart rate with bed sensor.
AB  - INTRODUCTION: This article is part of the Focus Theme of Methods of Information
      in Medicine on "Biosignal Interpretation: Advanced Methods for Studying
      Cardiovascular and Respiratory Systems". OBJECTIVES: The aim of this study is to
      assess the reliability of the estimated Nocturnal Heart Rate (HR), recorded
      through a bed sensor, compared with the one obtained from standard
      electrocardiography (ECG). METHODS: Twenty-eight sleep deprived patients were
      recorded for one night each through matrix of piezoelectric sensors, integrated
      into the mattress, through polysomnography (PSG) simultaneously. The two
      recording methods have been compared in terms of signal quality and differences
      in heart beat detection. RESULTS: On average, coverage of 92.7% of the total
      sleep time was obtained for the bed sensor, testifying the good quality of the
      recordings. The average beat-to-beat error of the inter-beat intervals was 1.06%.
      These results suggest a good overall signal quality, however, considering fast
      heart rates (HR > 100 bpm), performances were worse: in fact, the sensitivity in
      the heart beat detection was 28.4% while the false positive rate was 3.8% which
      means that a large amount of fast beats were not detected. CONCLUSIONS: The
      accuracy of the measurements made using the bed sensor has less than 10% of
      failure rate especially in periods with HR lower than 70 bpm. For fast heart
      beats the uncertainty increases. This can be explained by the change in
      morphology of the bed sensor signal in correspondence of a higher HR.

PMID- 24889151
TI  - Effectiveness of Psychotherapy in Personality Disorders Not Otherwise Specified:
      A Comparison of Different Treatment Modalities.
AB  - OBJECTIVE: Although personality disorder not otherwise specified (PDNOS) is
      highly prevalent and associated with a high burden of disease, only a few
      treatment studies in this patient group exist. This study is the first to
      investigate the effectiveness of different modalities of psychotherapy in
      patients with PDNOS, i.e., short-term (up to 6 months) and long-term (more than 6
      months) outpatient, day hospital, and inpatient psychotherapy. METHOD: A total of
      205 patients with PDNOS were assigned to one of six treatment modalities.
      Effectiveness was assessed over 60 months after baseline. The primary outcome
      measure was symptom severity, and the secondary outcome measures included
      psychosocial functioning and quality of life. The study design was quasi
      experimental, and the multiple propensity score was used to control for initial
      differences between treatment groups. RESULTS: All treatment modalities showed
      positive outcomes, especially in terms of improvements of symptom severity and
      social role functioning. At 12-month follow-up, after adjustment for initial
      differences between the treatment groups, short-term outpatient psychotherapy and
      short-term inpatient psychotherapy showed most improvement and generally
      outperformed the other modalities concerning symptom severity. At 60 months after
      baseline, effectiveness remained but observed differences between modalities
      mostly diminished. CONCLUSION: Patients with PDNOS benefit from psychotherapy
      both at short-term and long-term follow-up. Short-term outpatient psychotherapy
      and short-term inpatient psychotherapy seem to be superior to the other treatment
      modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly
      comparable effectiveness. KEY PRACTITIONER MESSAGES: The effectiveness of
      different modalities of psychotherapy in patients with PDNOS (i.e., short-term vs
      long-term; outpatient versus day hospital versus inpatient psychotherapy) has not
      yet been compared. Different modalities of psychotherapy are effective for
      patients with PDNOS, and positive effects remain after 5 years. In patients with
      PDNOS short-term (less than 6 months) outpatient psychotherapy and short-term
      inpatient psychotherapy seem to be superior to the four other treatment
      modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly
      comparable effectiveness.

PMID- 24889153
TI  - Exploitation of viral properties for intracellular delivery.
AB  - Nanotechnology is an expanding area of study with potentially pivotal
      applications in a discipline as medicine where new biomedical active molecules or
      strategies are continuously developing. One of the principal drawbacks for the
      application of new therapies is the difficulty to cross membranes that represent
      the main physiological barrier in our body and in all living cells. Membranes are
      selectively permeable and allow the selective internalization of substances;
      generally, they form a highly impermeable barrier to most polar and charged
      molecules, and represent an obstacle for drug delivery, limiting absorption to
      specific routes and mechanisms. Viruses provide attracting suggestions for the
      development of targeted drug carriers as they have evolved naturally to deliver
      their genomes to host cells with high fidelity. A detailed understanding of virus
      structure and their mechanisms of entry into mammalian cells will facilitate the
      development and analysis of virus-based materials for medical applications.

PMID- 24889154
TI  - Particle radiosurgery: a new frontier of physics in medicine.
AB  - Radiosurgery was introduced over half a century ago for treatment of intracranial
      lesions. In more recent years, stereotactic radiotherapy has rapidly advanced and
      is now commonly used for treatments of both cranial and extracranial lesions with
      high doses delivered in a few, down to a single fraction. The results of a
      workshop on Particle radiosurgery: A new frontier of physics in medicine held at
      Obergurgl, Austria during August 25-29 2013 are summarized in this issue with an
      overview presented in this paper. The focus was laid on particle radiosurgery but
      the content also includes current practice in x-ray radiosurgery and the
      overarching research in radiobiology and motion management for extracranial
      lesions. The results and discussions showed that especially research in
      radiobiology of high-dose charged-particles and motion management are necessary
      for the success of particle radiosurgery. 

PMID- 24889155
TI  - Radiosurgery in trigeminal neuralgia.
AB  - Trigeminal neuralgia is a rare but debilitating pain syndrome with a distinct
      clinical presentation mainly affecting people advancing in years. Compression of
      the trigeminal nerve by an aberrant vascular loop has been proposed as the
      causative factor in the majority of cases leading to the development of a highly
      effective surgical treatment approach termed "microvascular decompression".
      Nevertheless the mainstay of treatment remains medical. This article gives a
      brief overview of current treatment options for trigeminal neuralgia with special
      emphasis on radiosurgery. Possible mechanisms underlying the therapeutic effect
      of radiosurgery are discussed with some consideration of implications for
      optimizing prescription dose and target definition. 

PMID- 24889152
TI  - Genome-wide survey of tissue-specific microRNA and transcription factor
      regulatory networks in 12 tissues.
AB  - Tissue-specific miRNAs (TS miRNA) specifically expressed in particular tissues
      play an important role in tissue identity, differentiation and function. However,
      transcription factor (TF) and TS miRNA regulatory networks across multiple
      tissues have not been systematically studied. Here, we manually extracted 116 TS
      miRNAs and systematically investigated the regulatory network of TF-TS miRNA in
      12 human tissues. We identified 2,347 TF-TS miRNA regulatory relations and
      revealed that most TF binding sites tend to enrich close to the transcription
      start site of TS miRNAs. Furthermore, we found TS miRNAs were regulated widely by
      non-tissue specific TFs and the tissue-specific expression level of TF have a
      close relationship with TF-genes regulation. Finally, we describe TSmiR
      (http://bioeng.swjtu.edu.cn/TSmiR), a novel and web-searchable database that
      houses interaction maps of TF-TS miRNA in 12 tissues. Taken together, these
      observations provide a new suggestion to better understand the regulatory network
      and mechanisms of TF-TS miRNAs underlying different tissues. 

PMID- 24889156
TI  - Absence of maternal cell contamination in mesenchymal stromal cell cultures
      derived from equine umbilical cord tissue.
AB  - This study aimed to determine whether maternal cell contamination exists in cells
      derived from equine umbilical cord tissue, a perspective material for cell-based
      therapies in veterinary medicine. Potential maternal cell contamination was
      analyzed at DNA level via a set of 16 microsatellite markers in cells originating
      from the cord tissue of 22 foals. In these cells no maternal cell contamination
      was detected at a sensitivity level of 0.01%. Our results suggest that equine
      umbilical cord tissue-derived cells are entirely of fetal origin.

PMID- 24889159
TI  - Fragmentation of sperm DNA using the TUNEL method.
AB  - OBJECTIVES: To establish the validity of the TUNEL assay in determining sperm DNA
      fragmentation, the relationship between the degree of fragmentation and the
      seminal parameters and the sample needed to conduct the test. MATERIAL AND
      METHODS: We used semen samples from healthy fertile men (n=33), patients who
      consulted for infertility with a prescription for the TUNEL assay (n=77) and
      patients with intracytoplasmic sperm injection failure (n=20), analyzed according
      to the 2010 WHO. The TUNEL/propidium iodide test was performed by flow cytometry,
      on baseline and post-swim-up samples. RESULTS: The cutoff value for the TUNEL
      assay (ROC curves) was 26%, with a sensitivity and specificity of 85% and 89%,
      respectively. The pre-swim-up and post-swim-up medians of the results from the
      TUNEL assay showed no significant differences (17.0% vs. 12.9%, respectively).
      However, 39.1% of the samples showed a difference greater than 15 in absolute
      value between the results of the baseline and post-swim-up TUNEL assays. The
      linear correlation study of the morphology, mobility and vitality using the post
      swim-up TUNEL assay showed a greater correlation than preselection, with
      significant results (r: -0.394, P<.0001; r: -0.461, P<.0001; r: -0.526, P<.0001).
      CONCLUSIONS: The TUNEL assay is a valid test for clinical use. DNA fragmentation
      is a factor independent from traditional semen tests. We found a greater
      susceptibility to damage generated in the laboratory procedures in the samples
      with lower quality. The sample of choice for evaluating DNA fragmentation will
      depend on whether the clinician is treating a natural or assisted fertilization.

PMID- 24889160
TI  - The challenge of urinary tract infections.

PMID- 24889158
TI  - Phenotypical and ultrastructural features of Oct4-positive cells in the adult
      mouse lung.
AB  - Octamer binding trascription factor 4 (Oct4) is a transcription factor of POU
      family specifically expressed in embryonic stem cells (ESCs). A role for
      maintaining pluripotency and self-renewal of ESCs is assigned to Oct4 as a
      pluripotency marker. Oct4 can also be detected in adult stem cells such as bone
      marrow-derived mesenchymal stem cells. Several studies suggest a role for Oct4 in
      sustaining self-renewal capacity of adult stem cells. However, Oct4 gene ablation
      in adult stem cells revealed no abnormalities in tissue turnover or regenerative
      capacity. In the present study we have conspicuously found pulmonary Oct4
      positive cells closely resembling the morphology of telocytes (TCs). These cells
      were found in the perivascular and peribronchial areas and their presence and
      location were confirmed by electron microscopy. Moreover, we have used Oct4-GFP
      transgenic mice which revealed a similar localization of the Oct4-GFP signal. We
      also found that Oct4 co-localized with several described TC markers such as
      vimentin, Sca-1, platelet-derived growth factor receptor-beta C-kit and VEGF. By
      flow cytometry analyses carried out with Oct4-GFP reporter mice, we described a
      population of EpCAM(neg) /CD45(neg) /Oct4-GFP(pos) that in culture displayed TC
      features. These results were supported by qRT-PCR with mRNA isolated from lungs
      by using laser capture microdissection. In addition, Oct4-positive cells were
      found to express Nanog and Klf4 mRNA. It is concluded for the first time that TCs
      in adult lung mouse tissue comprise Oct4-positive cells, which express
      pluripotency-related genes and represent therefore a population of adult stem
      cells which might contribute to lung regeneration. 

PMID- 24889161
TI  - Cancer and body height.
AB  - OBJECTIVE: To test the hypothesis that body-resonant radiation may explain the
      correlation between body height and cancer risk observed in most countries around
      the world. METHODS: Data on cancer incidence and body height were collected from
      different countries and also from different regions within Sweden. Information on
      local FM broadcasting transmitters was also collected in Sweden to determine
      whether they correlated with the cancer incidence and body heights reported in
      each geographical area. Because broadcasting radiation may be concentrated by
      metal spring mattresses, we also attempted to collect information on the use of
      these mattresses in different parts of the world. RESULTS: A strong association
      was found between melanoma incidence and body height, both in different countries
      and in different municipalities within Sweden. At the same time, a very strong
      association was found between cancer incidence, mean body height, and the
      effective number of FM transmitters covering a given locality. Available data on
      the use of metal spring mattresses in different parts of the world also
      correlated well with data on cancer rates and body heights. CONCLUSIONS: The
      hypothesis that body-resonant radiation may affect both cancer incidence and body
      height was supported by the strong associations found in this study. The
      hypothesis was further supported by the correlation found between the incidence
      of cancer, body height, and the use of metal spring mattresses.

PMID- 24889163
TI  - Molecular imaging reveals epileptogenic Ca2+-channel promoter activation in
      hippocampi of living mice.
AB  - Focal epilepsies often originate in the hippocampal formation of the temporal
      lobe (temporal lobe epilepsy) and are generally acquired after transient brain
      insults. Such insults induce cellular and structural reorganization processes of
      the hippocampus, referred to as epileptogenesis that finally convert the brain
      spontaneous epileptic. Here, we developed a new molecular imaging strategy in a
      state-of-the-art animal model to provide insights into key epileptogenic
      mechanisms. Our new approach combines recombinant adeno-associated virus (rAAV)
      gene delivery with in vivo bioluminescence imaging. rAAV particles harboring the
      luciferase reporter gene under control of the minimal T type Ca(2+)-channel
      subunit Ca V 3.2-promoter were generated and injected stereotaxically in the
      hippocampal region of mice. Bioluminescent signals, corresponding to Ca V 3.2
      promoter activation, were imaged in vivo in the pilocarpine model of status
      epilepticus (SE). We detected activation of key Ca V 3.2 promoter motifs at 3 and
      10 days after SE but not after the onset of chronic seizures. These data suggest
      Ca V 3.2 promoter activation as novel anti-epileptogenic target. In more general
      terms, we have established an experimental approach that allows to follow
      cerebral gene promoter dynamics longitudinally and to correlate this activity to
      behavioral parameters in the same mice.

PMID- 24889164
TI  - Body MR imaging: fast, efficient, and comprehensive.
AB  - Magnetic resonance (MR) imaging plays an important role in assessment of the full
      range of abdominal disease. The appropriate use of cooperative and motion
      resistant protocols can allow accurate determination of the character of focal
      lesions in the abdomen under most circumstances. This article discusses current
      MR techniques and the proper use of MR imaging in the diagnostic evaluation of
      cooperative and noncooperative patients. 

PMID- 24889165
TI  - Gadolinium contrast agent selection and optimal use for body MR imaging.
AB  - Proper selection of a gadolinium-based contrast agent (GBCA) for body magnetic
      resonance imaging (MRI) cases requires understanding the indication for the MRI
      exam, the key features of the different GBCAs, and the effect that the GBCA has
      on the selected imaging protocol. The different categories of GBCAs require
      timing optimization on postcontrast sequences and adjusting imaging parameters to
      obtain the highest T1 contrast. Gadoxetate disodium has many advantages when
      evaluating liver lesions, although there are caveats and limitations that need to
      be understood. Gadobenate dimeglumine, a high-relaxivity GBCA, can be used for
      indications when stronger T1 relaxivity is needed. 

PMID- 24889162
TI  - Reorganization of supramammillary-hippocampal pathways in the rat pilocarpine
      model of temporal lobe epilepsy: evidence for axon terminal sprouting.
AB  - In mesial temporal lobe epilepsy (MTLE), spontaneous seizures likely originate
      from a multi-structural epileptogenic zone, including several regions of the
      limbic system connected to the hippocampal formation. In this study, we
      investigate the structural connectivity between the supramammillary nucleus (SuM)
      and the dentate gyrus (DG) in the model of MTLE induced by pilocarpine in the
      rat. This hypothalamic nucleus, which provides major extracortical projections to
      the hippocampal formation, plays a key role in the regulation of several
      hippocampus-dependent activities, including theta rhythms, memory function and
      emotional behavior, such as stress and anxiety, functions that are known to be
      altered in MTLE. Our findings demonstrate a marked reorganization of DG afferents
      originating from the SuM in pilocarpine-treated rats. This reorganization, which
      starts during the latent period, is massive when animals become epileptic and
      continue to evolve during epilepsy. It is characterized by an aberrant
      distribution and an increased number of axon terminals from neurons of both
      lateral and medial regions of the SuM, invading the entire inner molecular layer
      of the DG. This reorganization, which reflects an axon terminal sprouting from
      SuM neurons, could contribute to trigger spontaneous seizures within an altered
      hippocampal intrinsic circuitry. 

PMID- 24889166
TI  - MR imaging of benign focal liver lesions.
AB  - Focal liver lesions (FLLs) are commonly encountered on routine imaging studies.
      Most lesions detected are benign, but many are indeterminate at the time of
      initial imaging. This article reviews the important role of MR imaging for the
      detection and characterization of various benign FLLs while illustrating typical
      imaging appearances and potential pitfalls in interpretation. The utility of
      diffusion-weighted imaging and hepatocyte-specific contrast agents is also
      discussed. 

PMID- 24889167
TI  - Hepatocellular carcinoma and other hepatic malignancies: MR imaging.
AB  - Magnetic resonance (MR) imaging surpasses all other imaging modalities in
      characterizing liver lesions by virtue of the exquisite tissue contrast,
      specificity for various tissue types, and extreme sensitivity to contrast
      enhancement. In addition to differentiating benign from malignant lesions, MR
      imaging generally discriminates between the various malignant liver lesions.
      Hepatocellular carcinoma constitutes most primary malignant liver lesions and
      usually arises in the setting of cirrhosis. Intrahepatic cholangiocarcinoma is a
      distant second and features distinctly different imaging features. Overall,
      metastases are the most common malignant liver lesions and arise from several
      primary neoplasms; most commonly gastrointestinal, lung, breast, and
      genitourinary. 

PMID- 24889168
TI  - MR imaging of diffuse liver disease: from technique to diagnosis.
AB  - Over the past decade the role of MR imaging in the evaluation of diffuse liver
      disease has become common practice. Although detection of focal liver lesions
      remains the mainstay of liver imaging, a growing cohort of patients are referred
      for evaluation of hepatosteatosis, iron deposition diseases, and cirrhosis. In
      particular, multiecho sequences are becoming the gold standard for quantification
      of fat and iron. MR elastography allows for improved early detection of hepatic
      fibrosis. Unfortunately, a majority of the diffuse liver diseases lack specific
      features on MR imaging, yet a solid understanding of the different pathologic
      processes allows an informed interpretation. 

PMID- 24889169
TI  - MR imaging of the biliary system.
AB  - Although ultrasound, computed tomography, and cholescintigraphy play essential
      roles in the evaluation of suspected biliary abnormalities, magnetic resonance
      (MR) imaging and MR cholangiopancreatography can be used to evaluate inconclusive
      findings and provide a comprehensive noninvasive assessment of the biliary tract
      and gallbladder. This article reviews standard MR and MR cholangiopancreatography
      techniques, clinical applications, and pitfalls. Normal biliary anatomy and
      variants are discussed, particularly as they pertain to preoperative planning. A
      spectrum of benign and malignant biliary processes is reviewed, emphasizing MR
      findings that aid in characterization. 

PMID- 24889170
TI  - MR imaging of the pancreas.
AB  - Magnetic resonance (MR) imaging of the pancreas is useful as both a problem
      solving tool and an initial imaging examination of choice. With newer imaging
      sequences such as diffusion-weighted imaging, MR offers improved ability to
      detect and characterize lesions and identify and stage tumors and inflammation.
      MR cholangiopancreatography can be used to visualize the pancreatic and biliary
      ductal system. In this article, the use of MR to evaluate the pancreas, including
      recent advances, is reviewed and the normal appearance of the pancreas on
      different imaging sequences, as well as inflammatory diseases, congenital
      abnormalities, and neoplasms of the pancreas, are discussed. 

PMID- 24889171
TI  - MR imaging of the kidneys and adrenal glands.
AB  - MR imaging has proven to be a versatile modality in evaluation of the kidneys,
      collecting system, and adrenal glands. By performing a comprehensive MR
      examination, it is not only possible to accurately characterize cystic and solid
      lesions of the kidneys, as well as urothelial masses, but also to provide
      important preoperative information to the surgeon. In addition, MR imaging can
      characterize many adrenal lesions and can frequently obviate biopsy. The
      continued development and growth of MR technology combined with the current trend
      toward minimally invasive surgery will expand the role of MR imaging in the
      future. 

PMID- 24889172
TI  - MR enterography for assessment and management of small bowel Crohn disease.
AB  - Magnetic resonance enterography (MRE) utilization has increased for the
      evaluation of small bowel diseases over the last several years. In addition to
      performing similarly to computed tomography enterography (CTE) in the evaluation
      of inflammatory bowel disease, MRE lacks ionizing radiation, can image the small
      bowel dynamically, and provides excellent soft tissue contrast resolution. This
      article reviews imaging protocols for MRE, normal MR imaging appearance of small
      bowel, and the imaging findings of small bowel Crohn disease. The importance of
      imaging findings for directing management in patients with small bowel Crohn
      disease is emphasized throughout. 

PMID- 24889173
TI  - MR imaging of the prostate.
AB  - Multiparametric magnetic resonance (MR) imaging of the prostate is gaining
      acceptance in the management of prostate cancer. Emerging indications of prostate
      MR imaging may expand its use in the work-up of localized prostate cancer.
      Improvements in the standardization of prostate MR imaging techniques and
      reporting are needed for further establishment of the emerging roles of prostate
      MR imaging. This article describes the prostate MR imaging techniques and
      provides an approach for interpretation of prostate MR imaging studies.
      Established and emerging indications for prostate MR imaging are also reviewed. 

PMID- 24889174
TI  - MR angiography of the abdomen and pelvis.
AB  - Magnetic resonance (MR) angiographic techniques optimize the visualization of the
      vasculature at MR imaging. MR angiography has several advantages over Doppler
      ultrsonography and computed tomographic angiography, with adaptable protocols to
      answer specific clinical questions. Novel noncontrast MR angiographic techniques
      now enable assessment of the abdominopelvic vasculature without administration of
      gadolinium-based contrast media. This article reviews MR angiographic techniques
      and discusses applications for arterial and venous evaluation in the abdomen and
      pelvis. 

PMID- 24889175
TI  - Dealing with vascular conundrums with MR imaging.
AB  - Magnetic resonance (MR) imaging is a robust imaging modality for evaluation of
      vascular diseases. Technological advances have made MR imaging widely available
      for accurate and time-efficient vascular assessment. In this article the clinical
      usefulness of MR imaging techniques and their application are reviewed, using
      examples of vascular abnormalities commonly encountered in clinical practice,
      including abdominal, pelvic, and thoracic vessels. Common pitfalls and problem
      solving in interpretation of vascular findings in body MR imaging are also
      discussed. 

PMID- 24889176
TI  - Functional MR imaging of the abdomen.
AB  - In this article, functional magnetic resonance (MR) imaging techniques in the
      abdomen are discussed. Diffusion-weighted imaging (DWI) increases the confidence
      in detecting and characterizing focal hepatic lesions. The potential uses of DWI
      in kidneys, adrenal glands, bowel, and pancreas are outlined. Studies have shown
      potential use of quantitative dynamic contrast-enhanced MR imaging parameters,
      such as K(trans), in predicting outcomes in cancer therapy. MR elastography is
      considered to be a useful tool in staging liver fibrosis. A major issue with all
      functional MR imaging techniques is the lack of standardization of the protocol. 

PMID- 24889177
TI  - Radiologic Clinics of North America. Adult body MR. Preface.

PMID- 24889178
TI  - Diverse transformations of liquid metals between different morphologies.
AB  - Transformation from a film into a sphere, rapid merging of separate objects,
      controlled self-rotation, and planar locomotion are the very unusual phenomena
      observed in liquid metals under application of an electric field to a liquid
      metal immersed in or sprayed with water. A mechanism for these effects is
      suggested and potential applications - for example the recovery of liquid metal
      previously injected into the body for therapeutic purposes - are outlined. 

PMID- 24889179
TI  - Assessment of chloroquine as a modulator of immune activation to improve CD4
      recovery in immune nonresponding HIV-infected patients receiving antiretroviral
      therapy.
AB  - OBJECTIVES: Chloroquine (CQ), an anti-inflammatory drug, inhibits Toll-like
      receptor (TLR) signalling in plasmacytoid dendritic cells (pDCs) and may be
      beneficial for HIV-infected patients in whom immune activation persists despite
      effective antiretroviral therapy (ART). The effect of CQ on CD4 T-cell recovery
      and immune activation in immune nonresponding patients receiving successful ART
      was therefore studied. METHODS: Nineteen adults on ART with CD4 counts <= 350
      cells/MUL and undetectable viral load (VL) orally received CQ at 250 mg/day for
      24 weeks. Side effects, CD4 and CD8 T-cell counts, VL, T-cell activation, pDC
      proportion and plasma inflammatory markers were assessed at baseline, at 24
      weeks, and at 12 weeks after CQ discontinuation (clinicaltrial.org registration
      #NCT02004314). RESULTS: CQ was well tolerated and all patients maintained an
      undetectable VL. The absolute CD4 and CD8 T-cell counts and their percentages,
      the pDC proportion, T-cell activation, D-dimer and C-reactive protein (CRP)
      plasma levels and the kynurenine/tryptophan ratio did not change with CQ
      treatment. Among nine cytokines/chemokines measured, only levels of interferon
      (IFN)-alpha2 were significantly increased by CQ treatment. CONCLUSIONS: CQ was
      well tolerated in patients with low CD4 T-cell counts despite long-term effective
      ART; however, 24 weeks of CQ treatment did not improved CD4 T-cell recovery,
      lymphoid and myeloid immune activation or inflammatory markers.

PMID- 24889180
TI  - Large-scale gene expression profiling data for the model moss Physcomitrella
      patens aid understanding of developmental progression, culture and stress
      conditions.
AB  - The moss Physcomitrella patens is an important model organism for studying plant
      evolution, development, physiology and biotechnology. Here we have generated
      microarray gene expression data covering the principal developmental stages,
      culture forms and some environmental/stress conditions. Example analyses of
      developmental stages and growth conditions as well as abiotic stress treatments
      demonstrate that (i) growth stage is dominant over culture conditions, (ii)
      liquid culture is not stressful for the plant, (iii) low pH might aid
      protoplastation by reduced expression of cell wall structure genes, (iv) largely
      the same gene pool mediates response to dehydration and rehydration, and (v)
      AP2/EREBP transcription factors play important roles in stress response
      reactions. With regard to the AP2 gene family, phylogenetic analysis and
      comparison with Arabidopsis thaliana shows commonalities as well as uniquely
      expressed family members under drought, light perturbations and protoplastation.
      Gene expression profiles for P. patens are available for the scientific community
      via the easy-to-use tool at https://www.genevestigator.com. By providing large
      scale expression profiles, the usability of this model organism is further
      enhanced, for example by enabling selection of control genes for quantitative
      real-time PCR. Now, gene expression levels across a broad range of conditions can
      be accessed online for P. patens. 

PMID- 24889181
TI  - CYP2C9 allelic variants and frequencies in a pediatric sickle cell disease
      cohort: implications for NSAIDs pharmacotherapy.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain in patients with
      sickle cell disease (SCD) are metabolized by the CYP2C9 enzyme. Racial
      differences in CYP2C9 allele frequencies impact NSAIDs efficacy and safety. We
      determined the frequencies of CYP2C9 alleles in an African American pediatric SCD
      cohort. Genomic DNA was isolated from blood samples of 30 patients aged between 7
      and 17 years. Genotyping of nine CYP2C9 alleles (*1,*2, *3, *4, *5, *6, *8, *11,
      and *13) was performed using restriction fragment length polymorphism-PCR assays
      and the Tag-ItTM Mutation Detection System. The wild type *1 allele frequency was
      0.850. The most common variant allele detected was CYP2C9*8 (0.067). The combined
      frequency of the *2, *5, *6, *8, and *11 variants was 0.151. Seventy percent of
      the study cohort were predicted extensive metabolizers (*1/*1) and 30% were
      intermediate metabolizers due mainly to the *1/*8 genotype. Analysis of CYP2C9
      using an expanded assay panel facilitated improved classification of predicted
      drug metabolic phenotypes in our cohort. However, the pharmacokinetic effects of
      the CYP2C9*5,*6,*8, and *11 alleles on NSAIDs metabolism has not been evaluated
      and underscores the need for studies on substrate-specific effects of variant
      alleles common in populations with genetic susceptibility to SCD. 

PMID- 24889182
TI  - The effect of autopolymerizing acrylic resin thickness on the bond strength of a
      repaired denture tooth.
AB  - PURPOSE: This study analyzed the conventional method of rebonding a denture
      tooth, evaluating the effect of varied thickness of autopolymerizing acrylic
      resin on the bond strength and the failure mode. MATERIALS AND METHODS: A total
      of 52 heat-polymerizing acrylic resin specimens were fabricated with an anterior
      denture tooth. A cantilever-type bending force was applied with a universal
      testing machine to each specimen until failure. The failure mode was determined,
      and cohesive failures were excluded from part II. Thirty specimens were randomly
      selected and divided into three groups (n = 10). For each group, resin was
      relieved from the bonding area to create a 0, 1, or 3 mm space. The tooth was
      repositioned using its matrix and reattached to its base, filling the relieved
      space with autopolymerizing acrylic resin. The repaired specimens were tested
      using the same parameters. Data were analyzed with paired t-tests, one-way ANOVA,
      and post hoc test. Statistical significance was determined at p < 0.05. RESULTS:
      The mean peak load to failure for the part I group was 88.91 N. While the peak
      load to failure decreased to 71.96 N (19.69% loss of original bond strength),
      statistical analysis revealed no difference between the bond strength of the
      specimens repaired with a 0 mm thickness of autopolymerizing acrylic resin and
      the original (part I) group (p > 0.05). The bond strength was lower for the group
      repaired with a 1 mm thickness compared to the original (part I) group (p <
      0.05), with 65.8 N load to failure (29.63% loss). The bond strength was even
      lower for the group repaired with a 3 mm thickness (p < 0.05), with 58.64 N load
      to failure (33.07% loss). Post hoc analysis revealed a significant difference
      between the 0 and 3 mm groups (p = 0.04). The most common failure mode in the
      original group was adhesive (56%), then combination (34%), then cohesive (9.8%).
      The repaired group (n = 30) had similar results, with 56.7% adhesive, 36.7%
      combination, and 6.7% cohesive failures. CONCLUSIONS: The bond strength of a
      replaced denture tooth is affected by the thickness of the autopolymerizing
      acrylic resin. The failure mode of a rebonded denture tooth follows the same
      trend of the original failure. If possible, replace teeth with no relief. If
      combination failure occurs, leave residual base acrylic resin on the ridge lap.

PMID- 24889183
TI  - Multifunctional redox polymers: electrochrome, polyelectrolyte, sensor, electrode
      modifier, nanoparticle stabilizer, and catalyst template.
AB  - Simple "click" polycondensation metallopolymers of redox-robust
      bis(ethynyl)biferrocene (biFc) and di(azido) poly(ethylene glycol) (PEG400 and
      PEG1000) were designed for multiple functions including improvement of water
      solubility and biocompatibility, the introduction of mixed valency and sensing
      capabilities, and as nanoparticle stabilizers for catalysis. 

PMID- 24889184
TI  - Factors affecting the rate of oxidation and resultant discolouration of
      tetracyclines contained in endodontic medicaments and irrigants.
AB  - AIM: To determine the effect of pH, oxygen levels and ions on tetracycline
      oxidation and resultant discolouration. METHODOLOGY: Solutions of demeclocycline
      hydrochloride or doxycycline hyclate were prepared and exposed to different pH
      conditions, pure oxygen or carbon dioxide, ascorbic acid or various ions (from
      calcium chloride, calcium nitrate, strontium chloride, magnesium chloride, zinc
      chloride, and bismuth nitrate). Subsequently, they were exposed to intense
      visible blue light (470 +/- 15 nm) for 24 h. Colour change was monitored using
      standardized digital photography. Parametric statistical analysis employing the
      Wilcoxon matched-pairs signed-rank test was performed to compare the mean change
      in different colour channels, assessing the discolouration effect of the modified
      conditions. RESULTS: An acidic pH reduced discolouration, whilst alkaline pH
      increased it. A higher oxygen tension resulted in more discolouration, as did the
      presence of calcium, strontium, and bismuth ions, all of which bind to
      tetracyclines. Conversely, zinc and magnesium ions had a mild photoprotective
      effect. Ascorbic acid, an anti-oxidant, reduced the level of discolouration.
      CONCLUSIONS: The tendency of these tetracyclines to undergo photo-oxidation is
      increased by common variables present in the clinical environment. There are
      potential benefits from using photoprotectors and anti-oxidants in these
      materials, to reduce the possibility of discolouration.

PMID- 24889185
TI  - Markers of lutein and zeaxanthin status in two age groups of men and women:
      dietary intake, serum concentrations, lipid profile and macular pigment optical
      density.
AB  - BACKGROUND & AIMS: Lutein and zeaxanthin accumulate in retina (macular pigment).
      Their nutritional status can be assessed using dietary or biochemical markers and
      both have been associated with macular pigment optical density. We proposed to
      assess dietary and status markers of lutein and zeaxanthin in a group of healthy
      Spanish volunteers, considering the potential influence of age, gender and serum
      lipids to investigate the predictors of the macular pigment optical density.
      METHODS: Serum lutein and zeaxanthin concentrations, dietary intake and macular
      pigment optical density were determined in 108 healthy men and women (20-35 and
      45-65 years), using high-performance liquid chromatography, 3-day food records
      and heterochromic flicker photometry, respectively. Mann-Whitney U-test, Spearman
      correlation coefficient and multivariate regression analysis were used for the
      statistical study. RESULTS: Serum concentrations and dietary intake of lutein
      plus zeaxanthin (p < 0.0001 and p = 0.001, respectively) were higher in older vs
      younger subjects, whereas macular pigment optical density was lower (p = 0.038).
      The highest correlation coefficients between intake and serum were for fruit and
      serum lutein (rho = 0.452, p < 0.0001) and for fruit and lutein + zeaxanthin (rho
      = 0.431, p < 0.0001) in the younger group. Macular pigment optical density
      correlated with serum xanthophylls (rho = 0.223, p = 0.02) and fruit and
      vegetable intake (rho = 0.350, p = 0.0002), showing highest correlations when
      lutein and zeaxanthin were expressed in relation to serum lipids in older
      subjects (rho = 0.262, p = 0.006). Multivariate regression analysis identified
      age and serum lutein as major predictors of macular pigment optical density
      (total sample), and a coefficient of determination of 29.7% for the model
      including lutein + zeaxathin/cholesterol + triglycerides, sex and fruit +
      vegetables in the older group. CONCLUSIONS: The establishment of normal/reference
      ranges for serum lutein and zeaxanthin should consider age ranges and be
      expressed in relation to lipid concentrations, at least in subjects over 45
      years, as this could influence macular pigment optical density. The macular
      pigment optical density showed age-specific correlations with lutein plus
      zeaxanthin expressed in relation to serum lipid concentrations as well as with
      the fruit and vegetable intake.

PMID- 24889186
TI  - Copper-catalyzed one-pot denitrogenative-dehydrogenative-decarboxylative coupling
      of beta-ketoacids with trifluorodiazoethane: facile access to trifluoromethylated
      aldol products.
AB  - A novel copper-catalyzed one-pot cross-coupling of beta-ketoacids with in situ
      generated trifluorodiazoethane has been developed. This reaction provides a
      direct and efficient method, in which one C-C bond and one C-O bond were formed
      in a carbenoid center with concomitant denitrogenation-dehydrogenation
      decarboxylation, to afford trifluoromethylated aldol products. In several
      preliminary experiments, good to high enantioselectivities were also obtained.

PMID- 24889187
TI  - Evaluation of different screw fixation techniques and screw diameters in sagittal
      split ramus osteotomy: finite element analysis method.
AB  - Sagittal split ramus osteotomy (SSRO) is used for correction of numerous
      congenital or acquired deformities in facial region. Several techniques have been
      developed and used to maintain fixation and stabilisation following SSRO
      application. In this study, the effects of the insertion formations of the
      bicortical different sized screws to the stresses generated by forces were
      studied. Three-dimensional finite elements analysis (FEA) and static linear
      analysis methods were used to investigate difference which would occur in terms
      of forces effecting onto the screws and transmitted to bone between different
      application areas. No significant difference was found between 1.5- and 2-mm
      screws used in SSRO fixation. Besides, it was found that 'inverted L' application
      was more successful compared to the others and that was followed by 'L' and
      'linear' formations which showed close rates to each other. Few studies have
      investigated the effect of thickness and application areas of bicortical screws.
      This study was performed on both advanced and regressed jaws positions.

PMID- 24889188
TI  - Prostaglandin E1 alleviates neuropathic pain and neural dysfunction from
      entrapment neuropathy associated with diabetes mellitus.
AB  - In this report, we present the results of investigation of the effects of
      prostaglandin E1 (PGE1) on entrapment neuropathy using a diabetic rat. A total of
      60 male Sprague-Dawley rats were used in the study. The model of tibial nerve
      entrapment neuropathy associated with diabetes mellitus was created by
      streptozotocin-induced diabetic rats reared in cages with wire grid flooring.
      Rats were assigned to four groups: nondiabetic (n = 15), untreated diabetic (n =
      15), diabetic treated with 30 MUg/kg PGE1 (n = 15), and diabetic treated with 100
      MUg/kg PGE1 (n = 15). Pain tests and electrophysiological tests were performed at
      0, 2, and 4 weeks, and assessments of gait, histology, and mRNA expression levels
      were performed at 4 weeks after initiating the PGE1 administration. In the 30 and
      100 MUg groups, the mechanical withdrawal thresholds measured by pain tests at 4
      weeks (36.2 +/- 16.4 g and 31.7 +/- 15.3 g, respectively) and the motor
      conduction velocity (24.0 +/- 0.2 m/s and 24.4 +/- 0.3 m/s, respectively) were
      significantly higher than the untreated diabetic group (all P < 0.05) and lower
      than the nondiabetic group (all P < 0.001). In the gait analysis, the mean
      intensities in the 30 and 100 MUg group (128.0 +/- 20.1 a.u. and 109.0 +/- 27.8
      a.u., respectively) were significantly higher than the untreated diabetic (P <
      0.01) and were not significantly different from the nondiabetic group (P = 0.81).
      Fiber density (P = 0.46) and fiber diameter (P = 0.15) did not show any
      significant differences. PGE1 significantly decreased nerve growth factor (NGF)
      mRNA and increased vascular endothelial growth factor (VEGF) mRNA in the tibial
      nerve (both P < 0.01). In conclusion, neurological deteriorations of diabetic
      rats were alleviated with PGE1, which is associated with inhibition of NGF and
      enhancement of VEGF at the entrapment site.

PMID- 24889189
TI  - Spectrum of histopathological changes encountered in stented colorectal
      carcinomas.
AB  - AIMS: Self-expanding metallic stents (SEMS) are increasingly being used in
      obstructing colorectal cancer (CRC) as a 'bridge to surgery', allowing conversion
      of potentially high-risk emergency resections to elective procedures. Stenting
      may cause a wide array of histological changes. We present the largest series to
      date of stented CRC, performed and reported at a single institution. METHODS AND
      RESULTS: Stented CRC specimens received in January 2006 to December 2011 were
      identified from our pathology database. Slides for each case were independently
      reviewed by two pathologists, and a consensus was reached. A total of 72 CRCs
      were identified, 15 at or proximal to the splenic flexure, and 57 left-sided.
      Thirty-six were stage pT3 and 36 were stage pT4. Perforation was observed in 14
      cases. The effects of stenting on the tumour included tumour necrosis (100%) and
      flat ulceration (77.8%). The spectrum of changes in the background bowel included
      mimics of inflammatory bowel disease, tumour regression post-neoadjuvant therapy,
      and ischaemia. CONCLUSIONS: Given the inclusion of stenting of CRC as a bridge to
      surgery in the current NICE guidelines, we expect to see increasing numbers of
      such cases. In our study, a range of changes were encountered that mimic other
      bowel diseases, from simple fissuring to chronic inflammatory bowel disease and
      neoadjuvant regression change.

PMID- 24889190
TI  - Sleep quality and the risk of work injury: a Swiss case-control study.
AB  - Sleep problems are a well-known risk factor for work injuries, but less is known
      about which vulnerable populations are most at risk. The aims of this study were
      to investigate the association between sleep quality and the risk of work injury
      and to identify factors that may modify the association. A case-control study
      including 180 cases and 551 controls was conducted at the University Hospital in
      Basel, Switzerland, from 1 December 2009 to 30 June 2011. Data on work injuries
      and sleep quality were collected. Adjusted odds ratios and 95% confidence
      intervals of the association between sleep quality and work injury were estimated
      in multivariable logistic regression analyses and were stratified by hypothesized
      effect modifiers (age, gender, job risk, shift work, sleep duration and working
      hours). Poor sleep quality was associated significantly with work injury of any
      type (P < 0.05) and with being caught in particular (P < 0.05). The association
      between poor sleep quality and work injury was significantly higher for workers
      older than 30 years (odds ratio>30 1.30 versus odds ratio<=30 0.91, P < 0.01),
      sleeping 7 h or less per night (odds ratio<=7 1.17 versus odds ratio>7 0.79, P <
      0.05) and working 50 h or more per week (odds ratio>=50 1.79 versus odd ratio<50
      1.10, P < 0.01). Work injury risk increased with increasing severity of sleep
      problems (P < 0.05). Prior work injury frequency increased with decreasing sleep
      quality (P < 0.05). Older age, short sleep duration and long working hours may
      enhance the risk of work injuries associated with sleep quality.

PMID- 24889191
TI  - Discrete dipole approximation analysis of plasmonic core/alloy nanoparticles.
AB  - The surface plasmon resonance (SPR) properties of Au/Au(x)Ag(1-x) core/alloy
      nanoparticles (NPs) have been investigated by means of the discrete dipole
      approximation. The core/alloy microstructure was varied by changing the shell
      alloy composition x, its thickness t(S), and the shell thickness to core radius
      ratio (t(S)/r(C)) in the range of 0.05-1.0. These changes resulted in a novel
      tuning of SPR shape, frequency, and extinction. These models were compared with
      experimental results for Au/Au(x)Ag(1-x) NPs prepared by a microwave-mediated
      hydrothermal processing method, which produces core/alloy NPs with SPR signatures
      closely resembling those of the models.

PMID- 24889192
TI  - Exercise mitigates diclofenac-induced liver mitochondrial dysfunction.
AB  - BACKGROUND: Several strategies have been developed to counteract liver injury as
      a consequence of nonsteroid anti-inflammatory drugs toxicity. Here, we aimed to
      determine whether physical exercise results in liver mitochondrial protection
      against in vitro diclofenac toxicity. MATERIAL AND METHODS: Male adult Sprague
      Dawley rats were divided into sedentary, 12-week endurance training (ET) and
      voluntary activity (VPA). In vitro liver mitochondrial function as assessed by
      oxygen consumption, transmembrane electric potential (DeltaPsi) and
      susceptibility to the mitochondrial permeability transition pore (MPTP) was
      evaluated in the absence and presence of diclofenac. Mitochondrial oxidative
      stress markers [MnSOD, aconitase, -SH and MDA, SIRT3, p66shc(Ser36)/p66shc ratio]
      and apoptotic signalling (caspases 3, 8 and 9, Bax, Bcl-2 and CypD) were
      assessed. Content of OXPHOS components and qualitative liver morphological
      evaluation were assessed. RESULTS: Despite no effects of ET and VPA on basal
      liver mitochondrial oxygen consumption or DeltaPsi endpoints, exercised animals
      showed lower susceptibility to MPTP. Diclofenac-induced decrease in DeltaPsi,
      increased state 4 respiration and susceptibility to MPTP opening were all
      prevented by exercise. Under untreated conditions, VPA group showed higher
      aconitase activity, while ET decreased MDA and increased Bax content. VPA
      decreased p66shc(Ser36), complex III and V OXPHOS subunits. Both ET and VPA
      increased complex IV OXPHOS subunit, and SIRT3 and Bcl-2 content and decreased
      caspase 9 activity. Unexpectedly, ET and VPA decreased ANT. CONCLUSIONS: Both
      chronic physical exercise models augmented the resistance to in vitro diclofenac
      induced mitochondrial alterations, including increased MPTP susceptibility,
      possibly by modulating oxidative stress and MPTP regulators.

PMID- 24889193
TI  - One hundred million adenosine-to-inosine RNA editing sites: hearing through the
      noise.
AB  - The most recent work toward compiling a comprehensive database of adenosine-to
      inosine RNA editing events suggests that the potential for RNA editing is much
      more pervasive than previously thought; indeed, it is manifest in more than 100
      million potential editing events located primarily within Alu repeat elements of
      the human transcriptome. Pairs of inverted Alu repeats are found in a substantial
      number of human genes, and when transcribed, they form long double-stranded RNA
      structures that serve as optimal substrates for RNA editing enzymes. A small
      subset of edited Alu elements has been shown to exhibit diverse functional roles
      in the regulation of alternative splicing, miRNA repression, and cis-regulation
      of distant RNA editing sites. The low level of editing for the remaining majority
      may be non-functional, yet their persistence in the primate genome provides
      enhanced genomic flexibility that may be required for adaptive evolution. 

PMID- 24889194
TI  - Deep sequencing reveals complex mechanisms of microRNA deregulation in colorectal
      cancer.
AB  - Deregulated microRNAs (miRNAs) have been reported to be of functional relevance
      for tumor biology. In this study, we analyzed the small RNA transcriptomes of 10
      paired colorectal cancer samples using SOLiD next-generation sequencing, and
      generated a total of >15141000 reads. miRNA expression profiles obtained by SOLiD
      sequencing correlated well with quantitative PCR results. The results showed that
      the expression of 36 miRNAs was significantly different between the two groups of
      samples. Additionally, we explored the global miRNA-mRNA interactions using a
      statistical model. In-depth analysis reveals a diagram of extensive post
      transcriptional miRNA regulations. Signaling pathways associated with the miRNA
      altered expression signature were identified using gene enrichment analysis. The
      results suggest that these microRNAs, in the aggregate, regulate signaling
      pathways, such as MAPK, Wnt and p53 pathways in cancer, which are known to be
      involved in the transformation of colorectal cancer. This evidence demonstrates
      that miRNAs can cooperatively regulate a given pathway and play a subtle role by
      regulating their target genes.

PMID- 24889195
TI  - Phosphorylation-dependent regulation of plant chromatin and chromatin-associated
      proteins.
AB  - In eukaryotes, most of the DNA is located in the nucleus where it is organized
      with histone proteins in a higher order structure as chromatin. Chromatin and
      chromatin-associated proteins contribute to DNA-related processes such as
      replication and transcription as well as epigenetic regulation. Protein functions
      are often regulated by PTMs among which phosphorylation is one of the most
      abundant PTM. Phosphorylation of proteins affects important properties, such as
      enzyme activity, protein stability, or subcellular localization. We here describe
      the main specificities of protein phosphorylation in plants and review the
      current knowledge on phosphorylation-dependent regulation of plant chromatin and
      chromatin-associated proteins. We also outline some future challenges to further
      elucidate protein phosphorylation and chromatin regulation.

PMID- 24889197
TI  - Green emitter copper clusters as highly efficient and reusable visible
      degradation photocatalysts.
AB  - Green emitter copper clusters (CuCLs) with a size of ~1.5 nm can be used as very
      efficient and recyclable photocatalysts for the degradation of methylene blue,
      both in solution and supported onto glass surface showing a photocatalytic
      efficiency larger than that found with common semiconductors. These results open
      a new important potential way to overcome major difficulties found in the
      photocatalysis field with the common semiconductors. 

PMID- 24889198
TI  - Type I female genital mutilation: a cause of completely closed vagina.
AB  - INTRODUCTION: Female genital mutilation (FGM) ranges in severity from a nick of
      the clitoris to partial or total removal of the external genitalia. Sexual
      complications after FGM include sexual dysfunction, difficult intercourse, and
      dyspareunia. AIM: We report a case of Type I FGM presenting as complete vaginal
      closure and urinary retention. METHODS: A 16-year-old adolescent was referred for
      obliterated vagina and urinary retention. She had recurrent urinary tract
      infections, difficulty in voiding, and cyclic hematuria. At the age of 1 year she
      had been taken by her mother to a pediatric surgeon to have a Type I FGM
      procedure. On examination, the urethral meatus and vaginal orifices were
      completely closed by the FGM scar. She underwent uneventful surgical opening of
      the vagina. RESULTS: A normal vaginal orifice was created and normal flow of
      urine and menses occurred. CONCLUSION: Type I FGM can present as complete vaginal
      closure and urinary retention. Proper diagnosis and treatment are of paramount
      importance.

PMID- 24889199
TI  - Venous air embolism detected on computed tomography of small animals.
AB  - OBJECTIVE: To describe the prevalence, location and clinical significance of
      abnormal gas accumulations in dogs and cats detected on computerised tomography
      images. METHODS: Retrospective evaluation of all canine and feline computed
      tomography examinations (292 pre-contrast and 219 post-contrast) performed in a
      12-month time period. All studies were evaluated for the presence of venous air
      emboli. The location of intravenous gas was noted and the volume of intravenous
      air emboli was estimated visually. The medical records of animals with venous air
      embolism were reviewed for signs of cardiopulmonary complications. RESULTS: The
      overall prevalence of air embolism on pre- and incidence on post-contrast images
      was 4 . 5 and 2 . 3%, respectively. The prevalence of air embolism on pre
      contrast and incidence on post-contrast thoracic images was 35 . 7 and 14 . 2%,
      respectively. The volume of venous air was generally small and the most common
      was in an axillary vein. None of the animals had any cardiopulmonary
      complications. CLINICAL SIGNIFICANCE: The presence of small volume venous air
      embolism on routine computed tomography examinations is a frequent incidental
      finding that does not appear to cause cardiopulmonary complications.

PMID- 24889196
TI  - Membrane protein profiling of human colon reveals distinct regional differences.
AB  - The colonic epithelium is a highly dynamic system important for the regulation of
      ion and water homeostasis via absorption and secretion and for the maintenance of
      a protective barrier between the outer milieu and the inside of the body. These
      processes are known to gradually change along the length of the colon, although a
      complete characterization at the protein level is lacking. We therefore analyzed
      the membrane proteome of isolated human (n = 4) colonic epithelial cells from
      biopsies obtained via routine colonoscopy for four segments along the large
      intestine: ascending, transverse, descending, and sigmoid colon. Label-free
      quantitative proteomic analyses using high-resolution mass spectrometry were
      performed on enriched membrane proteins. The results showed a stable level for
      the majority of membrane proteins but a distinct decrease in proteins associated
      with bacterial sensing, cation transport, and O-glycosylation in the proximal to
      distal regions. In contrast, proteins involved in microbial defense and anion
      transport showed an opposing gradient and increased toward the distal end. The
      gradient of ion-transporter proteins could be directly related to previously
      observed ion transport activities. All individual glycosyltransferases required
      for the O-glycosylation of the major colonic mucin MUC2 were observed and
      correlated with the known glycosylation variation along the colon axis. This is
      the first comprehensive quantitative dataset of membrane protein abundance along
      the human colon and will add to the knowledge of the physiological function of
      the different regions of the colonic mucosa. Mass spectrometry data have been
      deposited to the ProteomeXchange with the identifier PXD000987. 

PMID- 24889200
TI  - C4 -consumers in southern Europe: the case of Friuli V.G. (NE-Italy) during early
      and central Middle Ages.
AB  - Isotope variations were studied in necropolises of the early (6th to 7th century
      CE) and central (10th to 11th century CE) medieval period located in Fruili
      Venezia Giulia (Northeastern Italy). The two periods each shortly followed two
      great barbarian invasions that changed the politics and economy of Italy: the
      arrivals of Langobards in 578 CE and the Hungarian incursions from the end of the
      9th to the first half of the 10th century. These events had a tragic effect on
      the economy of Friuli-Venezia Giulia: severe depopulation and the partial
      abandonment of the countryside with fall of agricultural production.

PMID- 24889203
TI  - More evidence is needed to determine course of ex-drummer's death, judge rules.

PMID- 24889202
TI  - Leukotriene B4 amplifies eosinophil accumulation in response to nematodes.
AB  - Eosinophil accumulation is a defining feature of the immune response to parasitic
      worm infection. Tissue-resident cells, such as epithelial cells, are thought to
      initiate eosinophil recruitment. However, direct recognition of worms by
      eosinophils has not been explored as a mechanism for amplifying eosinophil
      accumulation. Here, we report that eosinophils rapidly migrate toward diverse
      nematode species in three-dimensional culture. These include the mammalian
      parasite Nippostrongylus brasiliensis and the free-living nematode Caenorhabditis
      elegans. Surprisingly, collective migration toward worms requires paracrine
      leukotriene B4 signaling between eosinophils. In contrast, neutrophils show a
      minimal response to nematodes, yet are able to undergo robust leukotriene
      dependent migration toward IgG-coated beads. We further demonstrate that
      eosinophils accumulate around C. elegans in the lungs of mice. This response is
      not dependent on bacterial products, CCR3, or complement activation. However,
      mice deficient in leukotriene signaling show markedly attenuated eosinophil
      accumulation after injection of C. elegans or N. brasiliensis. Our findings
      establish that nematode-derived signals can directly induce leukotriene
      production by eosinophils and that leukotriene signaling is a major contributor
      to nematode-induced eosinophil accumulation in the lung. The similarity of the
      eosinophil responses to diverse nematode species suggests that conserved features
      of nematodes are recognized during parasite infection.

PMID- 24889204
TI  - What is your diagnosis? Cerebrospinal fluid from a sheep.

PMID- 24889201
TI  - beta2 integrin mediates hantavirus-induced release of neutrophil extracellular
      traps.
AB  - Rodent-borne hantaviruses are emerging human pathogens that cause severe human
      disease. The underlying mechanisms are not well understood, as hantaviruses
      replicate in endothelial and epithelial cells without causing any cytopathic
      effect. We demonstrate that hantaviruses strongly stimulated neutrophils to
      release neutrophil extracellular traps (NETs). Hantavirus infection induced high
      systemic levels of circulating NETs in patients and this systemic NET overflow
      was accompanied by production of autoantibodies to nuclear antigens. Analysis of
      the responsible mechanism using neutrophils from beta2 null mice identified beta2
      integrin receptors as a master switch for NET induction. Further experiments
      suggested that beta2 integrin receptors such as complement receptor 3 (CR3) and 4
      (CR4) may act as novel hantavirus entry receptors. Using adenoviruses, we
      confirmed that viral interaction with beta2 integrin induced strong NET
      formation. Collectively, beta2 integrin-mediated systemic NET overflow is a novel
      viral mechanism of immunopathology that may be responsible for characteristic
      aspects of hantavirus-associated disease such as kidney and lung damage.

PMID- 24889205
TI  - Altered expression of hypoxia-Inducible factor-1alpha participates in the
      epileptogenesis in animal models.
AB  - Although epilepsy is a common neurological disorder, its mechanism(s) are still
      not completely understood. Hypoxia can lead to neuronal cell death and
      angiogenesis, and the same mechanisms were also found in epilepsy. Hypoxia
      inducible factor-1alpha (HIF-1alpha) is an important transcription protein that
      regulates gene expression in the brain and other tissues in response to decreases
      in oxygen availability. However, little is known regarding the expression of HIF
      1alpha in the epileptic brain and whether HIF-1alpha interventions affect the
      epileptic process. The aims of this study are to investigate the expression
      profile of HIF-1alpha in rat models and to explore the role of HIF-1alpha in
      epilepsy. We performed Western blots and immunofluorescence in a lithium
      pilocarpine rat epilepsy model. To determine the role of HIF-1alpha in epilepsy,
      we used the HIF-1alpha agonist DMOG and inhibitor KC7F2 to detect changes in the
      animal behavior in pentylenetetrazole (PTZ) and lithium-pilocarpine epilepsy
      models. The expression of HIF-1alpha was significantly increased after
      pilocarpine-induced status epilepticus. DMOG significantly prolonged the latent
      period in the PTZ kindling model and decreased the rate of spontaneous recurrent
      seizures during the chronic stage in the lithium-pilocarpine model. Conversely,
      the inhibitor KC7F2 produced an opposite behavioral change. Interestingly, both
      KC7F2 and DMOG had no effect on the acute stage of pilocarpine model and PTZ
      convulsive model. Our study suggests that upregulated HIF-1alpha may be involved
      in the process of epileptogenesis but not in the acute stage of epilepsy. The
      modulation of HIF-1alpha may offer a novel therapeutic target in epilepsy.

PMID- 24889206
TI  - ATP content, oxidative stress and motility of beluga (Huso huso) semen: effect of
      short-term storage.
AB  - An effective technique for short-term storage of semen is essential when
      processing multiple sperm samples and when semen must be transported from
      collection sites to hatcheries for the fertilization of ova or to laboratories
      for cryopreservation. In this experiment, beluga (Huso huso) sperm were used to
      evaluate the effects of short-term storage on several quality parameters (i.e.
      motility, adenosine triphosphate (ATP) content and oxidative stress indices).
      Sperm cells exhibited > 50% motility during 3 days of storage with an average
      total duration of sperm motility varying from 13.33 +/- 5.77 to 278.33 +/- 25.65
      s, and no motile spermatozoa were recorded after 9 days of storage. The levels of
      oxidative stress indices (thiobarbituric acid reactive substances and carbonyl
      derivatives of proteins) and antioxidant activity (superoxide dismutase)
      increased significantly after 3 days of storage. The ATP content also decreased
      significantly after 2 days of storage. The results of this study can be used to
      develop effective reproduction management and cryopreservation protocols for this
      endangered fish.

PMID- 24889208
TI  - Telemedicine and telesurgery in cancer care: inaugural conference at MD Anderson
      Cancer Center.
AB  - BACKGROUND: Despite the growing incidence of cancer worldwide, there are an
      insufficient number of primary care physicians, community oncologists, and
      surgeons to meet the demand for cancer care, especially in rural and other
      medically underserved areas. Teleoncology, including diagnostics, treatment, and
      supportive care, has the potential to enhance access to cancer care and to
      improve clinician education and training. OBJECTIVES: Major cancer centers such
      as The University of Texas MD Anderson Cancer Center must determine how
      teleoncology will be used as part of strategic planning for the future. The
      Telemedicine and Telesurgery in Cancer Care (TTCC) conference was convened to
      determine technologically based strategies for addressing global access to
      essential cancer care services. RESULTS: The TTCC conference brought policy
      makers together with physicians, legal and regulatory experts to define
      strategies to optimize available resources, including teleoncology, to advance
      global cancer care. CONCLUSIONS: The TTCC conference discourse provided insight
      into the present state of access to care, expertise, training, technology and
      other interventions, including teleoncology, currently available through MD
      Anderson, as well as a vision of what might be achievable in the future, and
      proposals for moving forward with a comprehensive strategy.

PMID- 24889207
TI  - Sleep restriction worsens mood and emotion regulation in adolescents.
AB  - BACKGROUND: The relationship between inadequate sleep and mood has been well
      established in adults and is supported primarily by correlational data in younger
      populations. Given that adolescents often experience shortened sleep on school
      nights, we sought to better understand the effect of experimentally induced
      chronic sleep restriction on adolescents' mood and mood regulation. METHODS:
      Fifty healthy adolescents, ages 14-17, completed a 3-week sleep manipulation
      protocol involving a baseline week, followed by a sleep restriction (SR)
      condition (6.5 hr in bed per night for five nights) and healthy sleep duration
      (HS) condition (10 hr in bed per night for five nights). The study used a
      randomized, counterbalanced, crossover experimental design. Participants' sleep
      was monitored at home via self-report and actigraphy. At the end of each
      condition, participants and their parents completed questionnaires of mood and
      mood regulation. To assess for expectancy effects, we also analyzed parent and
      teen ratings of hyperactivity/impulsivity, which prior research suggests is not
      sensitive to SR in adolescents. Wilcoxon Signed Rank tests compared questionnaire
      outcomes across the two conditions. RESULTS: Participants averaged 2.5 more hours
      of sleep per night during HS relative to SR. Compared with HS, adolescents rated
      themselves as significantly more tense/anxious, angry/hostile, confused, and
      fatigued, and as less vigorous (p = .001-.01) during SR. Parents and adolescents
      also reported greater oppositionality/irritability and poorer emotional
      regulation during SR compared with HS (p < .05). There were no cross-condition
      differences in depression or hyperactivity/impulsivity (p > .05). CONCLUSIONS:
      Findings complement prior correlational study results to show that after only a
      few days of shortened sleep, at a level of severity that is experienced regularly
      by millions of adolescents on school nights, adolescents have worsened mood and
      decreased ability to regulate negative emotions.

PMID- 24889209
TI  - Spin-orbital entangled molecular jeff states in lacunar spinel compounds.
AB  - The entanglement of the spin and orbital degrees of freedom through the spin
      orbit coupling has been actively studied in condensed matter physics. In several
      iridium oxide systems, the spin-orbital entangled state, identified by the
      effective angular momentum jeff, can host novel quantum phases. Here we show that
      a series of lacunar spinel compounds, GaM4X8 (M=Nb, Mo, Ta and W and X=S, Se and
      Te), gives rise to a molecular jeff state as a new spin-orbital composite on
      which the low-energy effective Hamiltonian is based. A wide range of electron
      correlations is accessible by tuning the bandwidth under external and/or chemical
      pressure, enabling us to investigate the cooperation between spin-orbit coupling
      and electron correlations. As illustrative examples, a two-dimensional
      topological insulating phase and an anisotropic spin Hamiltonian are investigated
      in the weak and strong coupling regimes, respectively. Our finding can provide an
      ideal platform for exploring jeff physics and the resulting emergent phenomena. 

PMID- 24889210
TI  - Influenza B outbreak on a cruise ship off the Sao Paulo Coast, Brazil.
AB  - BACKGROUND: In February 2012, crew and passengers of a cruise ship sailing off
      the coast of Sao Paulo, Brazil, were hospitalized for acute respiratory illness
      (ARI). A field investigation was performed to identify the disease involved and
      factors associated. METHODS: Information on passengers and crew with ARI was
      obtained from the medical records of hospitalized individuals. Active case
      finding was performed onboard the ship. ARI was defined as the presence of one
      nonspecific symptom (fever, chills, myalgia, arthralgia, headache, or malaise)
      and one respiratory symptom (cough, nasal congestion, sore throat, or dyspnea). A
      case-control study was conducted among the crew. The cases were crew members with
      symptoms of influenza-like illness (ILI) (fever and one of the following
      symptoms: cough, sore throat, and dyspnea) in February 2012. The controls were
      asymptomatic crew members. RESULTS: The study identified 104 ARI cases: 54
      (51.9%) crew members and 50 (49.1%) passengers. Among 11 ARI hospitalized cases,
      6 had influenza B virus isolated in nasopharyngeal swab. One mortality among
      these patients was caused by postinfluenza Staphylococcus aureus pneumonia. The
      crew members housed in the two lower decks and those belonging to the 18- to 32
      year-old age group were more likely to develop ILI [odds ratio (OR) = 2.39, 95%
      confidence interval (CI) 1.09-5.25 and OR = 3.72, CI 1.25-11.16, respectively].
      CONCLUSIONS: In February 2012, an influenza B outbreak occurred onboard a cruise
      ship. Among crew members, ILI was associated with lower cabin location and
      younger age group. This was the first influenza outbreak detected by Brazilian
      public health authorities in a vessel cruising in South American waters.

PMID- 24889211
TI  - Ultraviolet radiation induces stress in etiolated Landoltia punctata, as
      evidenced by the presence of alanine, a universal stress signal: a 15N NMR study.
AB  - Analysis with (15) N NMR revealed that alanine, a universal cellular stress
      signal, accumulates in etiolated duckweed plants exposed to 15-min pulsed UV
      light, but not in the absence of UV irradiation. The addition of 10 mm vitamin C,
      a radical scavenger, reduced alanine levels to zero, indicating the involvement
      of free radicals. Free D-alanine was detected in (15) N NMR analysis of the
      chiral amino acid content, using D-tartaric acid as solvent. The accumulation of
      D-alanine under stress conditions presents a new perspective on the biochemical
      processes taking place in prokaryote and eukaryote cells.

PMID- 24889213
TI  - A randomized pilot study of a comprehensive postoperative exercise program
      compared with usual care following primary total hip arthroplasty in subjects
      less than 65 years of age: feasibility, selection of outcome measures and timing
      of assessment.
AB  - BACKGROUND: Total Hip Arthroplasty (THA) is being used more commonly in younger
      higher demand patients. The purpose of this randomized pilot study was to explore
      a) feasibility of comprehensive postoperative rehabilitation compared to usual
      care following primary THA in subjects <65 years, b) appropriate outcome measures
      including performance-based measures and c) timing of assessments. METHODS: 21
      subjects who underwent primary THA were randomized to receive a three-month out
      patient rehabilitation program (Intervention) or usual postoperative care
      (Control). Subjects were assessed preoperatively, six-weeks postoperatively (Pre
      intervention) and four and 12 months postoperatively (Post-intervention). Self
      report measures were the Western Ontario McMaster Osteoarthritis Index (WOMAC)
      and Rand 36-Item Health Survey (RAND-36). Performance-based measures included
      lower extremity strength, walking speed and endurance, and gait laboratory
      assessment. RESULTS: Ten Control and 11 Intervention subjects with an average age
      of 53.4 (SD9.3) years were randomized. All Intervention subjects completed the
      program without adverse effects. Although no statistically significantly results
      were reported, four months postoperatively, Intervention subjects had clinically
      important differences (CID) in strength compared with Control subjects. Walking
      endurance, WOMAC and RAND scores improved significantly with no CID noted between
      groups. Ten (48%) subjects reported a ceiling effect on the WOMAC (9 (43%)
      subjects on Pain; 1 (5%) subject on Function). No group CID were noted in gait
      measures. CONCLUSIONS: Our recommendations would be that performance-based
      strength measures should be considered for the primary outcome in this younger
      cohort. Because of the ceiling effects with WOMAC Pain, a different pain measure
      is indicated. Other more challenging functional performance-based tests should be
      considered such as a more prolonged endurance test. There is merit in one-year
      follow-up as strength improved after four months in both groups.

PMID- 24889212
TI  - Systematic review: interactions between aspirin, and other nonsteroidal anti
      inflammatory drugs, and polymorphisms in relation to colorectal cancer.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin
      (acetylsalicylic acid, ASA). Long-term use of NSAIDs has been associated with
      lowered risk of colorectal cancer (CRC), but the use is hampered by adverse
      effects. Also, the anti-carcinogenic effects of NSAIDs are incompletely
      understood. Understanding biological effects of NSAIDs may help developing new
      preventive medical strategies. AIM: To identify gene-environment interactions
      between genetic variation and NSAID use in relation to risk of CRC. METHODS: We
      performed a PubMed literature search and all studies reporting original data on
      interactions between NSAIDs and polymorphisms in relation to CRC were evaluated.
      RESULTS: We found indications that aspirin interacted with rs6983267 close to MYC
      (encoding a transcription factor involved in cell cycle progression, apoptosis
      and cellular transformation) and NSAIDs interacted with rs3024505 and rs1800872
      in or close to IL10 (encoding IL-10) in preventing CRC. Homozygous carriers of
      the variant allele of rs6983267 (ca. 25% of the population) halved their risk for
      CRC by aspirin use compared to homozygous wildtype carriers who did not benefit
      from aspirin intake. No interaction between use of NSAIDs and PTGS-2 (encoding
      COX-2) in relation to CRC risk was detected. Other findings of interactions
      between genes in inflammatory and oncogenic pathways and NSAIDs were considered
      suggestive. CONCLUSIONS: Knowledge of underlying biological effects of NSAIDs in
      relation to CRC is scarce and the basis for stratifying the patients for
      preventive treatment is not yet available. Further studies assessing interactions
      between long-term NSAID exposure and genetic variation in relation to CRC are
      warranted in large well-characterised prospective cohorts.

PMID- 24889214
TI  - Molecular characterization of dengue viruses circulating during 2009-2012 in
      Uttar Pradesh, India.
AB  - Dengue is the most rapidly spreading mosquito-borne viral disease in the world;
      in India it has taken endemic proportion implicating all the four known dengue
      virus serotypes. Dengue infection is caused by a small, single stranded RNA virus
      comprising of four antigenically distinct virus serotypes designated as dengue
      virus type 1-4 (DENV-1-4). On the basis of genomic variations, each serotype is
      classified further into its genotypes. Epidemiological studies have shown that
      the emergence of a newer dengue serotype/genotype after an interval always leads
      to a major outbreak; therefore a continuous epidemiological surveillance is
      needed to monitor the epidemiology of dengue viruses. The present study was
      planned to identify the serotype/genotype of dengue viruses circulating in Uttar
      Pradesh, India. Of 433 dengue suspected patients, tested by reverse transcriptase
      PCR (RT-PCR), 136 were positive for dengue virus RNA. Of these, DENV-1, 2, and 3
      were detected in 26 (19.1%), 77 (56.6%), and 33 (24.3%) patients, respectively.
      Of 136 RT-PCR positive samples, 24 samples were sequenced to identify their
      genotypes. For sequencing C-prM gene junction of dengue virus genome was chosen.
      Phylogenetic analysis of sequenced dengue strains revealed that all the 12 DENV-1
      strains were genotype III, all the eight DENV-2 strains were genotype IV
      (Cosmopolitan genotype) and among four DENV-3 strains, three were genotype III
      and one was genotype I. In conclusion, the co-circulation of multiple dengue
      virus serotypes and genotypes is alarming in U.P., India.

PMID- 24889216
TI  - Quantifying the past and future impact of climate on outbreak patterns of bank
      voles (Myodes glareolus).
AB  - BACKGROUND: Central European outbreak populations of the bank vole (Myodes
      glareolus Schreber) are known to cause damage in forestry and to transmit the
      most common type of Hantavirus (Puumala virus, PUUV) to humans. A sound
      estimation of potential effects of future climate scenarios on population
      dynamics is a prerequisite for long-term management strategies. Historic
      abundance time series were used to identify the key weather conditions associated
      with bank vole abundance, and were extrapolated to future climate scenarios to
      derive potential long-term changes in bank vole abundance dynamics. RESULTS:
      Classification and regression tree analysis revealed the most relevant weather
      parameters associated with high and low bank vole abundances. Summer temperatures
      2 years prior to trapping had the highest impact on abundance fluctuation.
      Extrapolation of the identified parameters to future climate conditions revealed
      an increase in years with high vole abundance. CONCLUSION: Key weather patterns
      associated with vole abundance reflect the importance of superabundant food
      supply through masting to the occurrence of bank vole outbreaks. Owing to
      changing climate, these outbreaks are predicted potentially to increase in
      frequency 3-4-fold by the end of this century. This may negatively affect damage
      patterns in forestry and the risk of human PUUV infection in the long term.

PMID- 24889215
TI  - 4D optimization of scanned ion beam tracking therapy for moving tumors.
AB  - Motion mitigation strategies are needed to fully realize the theoretical
      advantages of scanned ion beam therapy for patients with moving tumors. The
      purpose of this study was to determine whether a new four-dimensional (4D)
      optimization approach for scanned-ion-beam tracking could reduce dose to
      avoidance volumes near a moving target while maintaining target dose coverage,
      compared to an existing 3D-optimized beam tracking approach. We tested these
      approaches computationally using a simple 4D geometrical phantom and a complex
      anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer
      patient. We also validated our findings using measurements of carbon-ion beams
      with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D
      optimized beam tracking reduced the maximum predicted dose to avoidance volumes
      by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam
      tracking provided similar target dose homogeneity in the simple phantom (standard
      deviation of target dose was 0.4% versus 0.3%) and dramatically superior
      homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements
      demonstrated that delivery of 4D-optimized beam tracking was technically feasible
      and confirmed a 42% decrease in maximum film exposure in the avoidance region
      compared with 3D-optimized beam tracking. In conclusion, we found that 4D
      optimized beam tracking can reduce the maximum dose to avoidance volumes near a
      moving target while maintaining target dose coverage, compared with 3D-optimized
      beam tracking. 

PMID- 24889217
TI  - Control of the misuse of testosterone in castrated horses based on an
      international threshold in plasma.
AB  - Testosterone is an endogenous steroid produced primarily in the testes. Trace
      levels of testosterone are found in urine samples from geldings, as testosterone
      is also secreted by the adrenal. An international threshold of free and
      conjugated testosterone in urine (20 ng/mL) was adopted by the International
      Federation of Horseracing Authorities (IFHA) in 1996 for controlling testosterone
      misuse in geldings. In view of the recent popularity of using blood in doping
      control testing, it is necessary to establish a threshold for testosterone in
      gelding plasma. A liquid chromatography-mass spectrometry (LC/MS) method was
      developed for quantifying low levels of free testosterone in gelding plasma.
      Based on a population study of 152 post-race plasma samples, the mean +/- SD
      concentration of plasma testosterone was determined to be 14.7 +/- 6.8 pg/mL.
      Normal distribution could be obtained after square-root or cube-root
      transformation, resulting in respective tentative thresholds of 49 or 55 pg/mL
      (corresponding to a risk factor of less than 1 in 10 000). A rounded-up threshold
      of 100 pg/mL of free testosterone in plasma was proposed. Based on the
      administration of Testosterone Suspension 100 to six geldings, the same average
      detection time of 14 days was observed in either plasma or urine using the
      proposed plasma threshold and the existing international urine threshold. The
      maximum detection time was 18 days in plasma and 20 days in urine. The results
      demonstrated the proposed plasma threshold is effective in controlling the misuse
      of testosterone in geldings. Similar results were subsequently obtained in
      Europe, and this proposed threshold was adopted by IFHA in October 2013.

PMID- 24889218
TI  - Establishment and characterization of a dairy goat mammary epithelial cell line
      with human telomerase (hT-MECs).
AB  - Although research on dairy goat mammary gland have referred extensively to
      molecular mechanisms, research on lines of dairy goat mammary epithelial cells
      (MECs) are still rare. This paper sought to establish an immortal MEC line by
      stable transfection of human telomerase. MECs from a lactating (45 days post
      parturition) Xinong Saanen dairy goat were cultured purely and subsequently
      transfected with a plasmid carrying the sequence of human telomerase.
      Immortalized MECs by human telomerase (hT-MECs) exhibited a typical cobblestone
      morphology and activity and expression levels of telomerase resembled that of MCF
      7 cells. hT-MECs on passage 42 grew vigorously and 'S' sigmoid curves of growth
      were observed. Moreover, hT-MECs maintained a normal chromosome modal number of
      2n=60, keratin 8 and epithelial membrane antigen (EMA) were evidently expressed,
      and beta-casein protein was synthesized and secreted. Beta-casein expression was
      enhanced by prolactin (P<0.05). Lipid droplets were found in hT-MECs, and
      messenger RNA levels of PPARG, SREBP, FASN, ACC and SCD in hT-MECs (passage 40)
      were similar to MECs (passage 7). In conclusion, the obtained hT-MEC line
      retained a normal morphology, growth characteristics, cytogenetics and secretory
      characteristics as primary MECs. Hence, it can be a representative model cell
      line, for molecular and functional analysis, of dairy goat MECs for an extended
      period of time.

PMID- 24889219
TI  - Will you thrive under pressure or burn out? Linking anxiety motivation and
      emotional exhaustion.
AB  - Can individual differences in the tendency to use anxiety as a source of
      motivation explain emotional exhaustion? We examined the effects of using anxiety
      as a source of energy or as a source of information (viewed here as two forms of
      anxiety motivation) on emotional exhaustion. In Study 1, the use of anxiety as a
      source of energy predicted decreased emotional exhaustion one year later.
      Moreover, both forms of anxiety motivation buffered people from the detrimental
      effects of trait anxiety on later emotional exhaustion. In Study 2, an
      experiment, participants who were instructed to use anxiety as a source of energy
      reported lower emotional exhaustion following a stressful task, compared to those
      instructed to focus on the task or to simply do their best. These findings
      suggest that using anxiety as a source of motivation may protect people against
      emotional exhaustion. 

PMID- 24889221
TI  - A phage-displayed peptide recognizing porcine aminopeptidase N is a potent small
      molecule inhibitor of PEDV entry.
AB  - Three phage-displayed peptides designated H, S and F that recognize porcine
      aminopeptidase N (pAPN), the cellular receptor of porcine transmissible
      gastroenteritis virus (TGEV) were able to inhibit cell infection by TGEV. These
      same peptides had no inhibitory effects on infection of Vero cells by porcine
      epidemic diarrhea virus (PEDV). However, when PEDV, TGEV and porcine pseudorabies
      virus were incubated with peptide H (HVTTTFAPPPPR), only infection of Vero cells
      by PEDV was inhibited. Immunofluoresence assays indicated that inhibition of PEDV
      infection by peptide H was independent of pAPN. Western blots demonstrated that
      peptide H interacted with PEDV spike protein and that pre-treatment of PEDV with
      peptide H led to a higher inhibition than synchronous incubation with cells.
      These results indicate direct interaction with the virus is necessary to inhibit
      infectivity. Temperature shift assays demonstrated that peptide H inhibited pre
      attachment of the virus to the cells. 

PMID- 24889222
TI  - XMRV low level of expression in human cells delays superinfection interference
      and allows proviral copies to accumulate.
AB  - Xenotropic Murine leukemia virus-Related Virus (XMRV) directly arose from genetic
      recombinations between two endogenous murine retroviruses that occurred during
      human xenografts in laboratory mice. Studies on XMRV could thus bring clues on
      how a new retrovirus could circumvent barrier species. We observed that XMRV
      exhibits a weak promoter activity in human cells, similar to the transcription
      level of a Tat-defective HIV-1. Despite this low fitness, XMRV can efficiently
      propagate through the huge accumulation of viral copies (~40 copies per cell)
      that compensates for the low expression level of individual proviruses. We
      further demonstrate that there is an inverse relationship between the maximum
      number of viral copies per infected cell and the level of viral expression, which
      is explained by viral envelope interference mechanisms. Low viral expression
      compensation by viral copy accumulation through delayed interference could a
      priori contribute to the propagation of others viruses following species jumps. 

PMID- 24889223
TI  - Ultrastructural fingerprints of avian influenza A (H7N9) virus in infected human
      lung cells.
AB  - In this study, we investigated the ultrastructural modifications induced by
      influenza A (H7N9) virus in human lung epithelial cells. One particular
      characteristic of H7N9 viral infection is the formation of numerous M1-associated
      striated tubular structures within the nucleus and the cytoplasm, which have only
      previously been observed for a limited number of influenza A viruses, notably the
      2009 pandemic (H1N1) virus. 

PMID- 24889220
TI  - Endocytosis-mediated HIV-1 entry and its significance in the elusive behavior of
      the virus in astrocytes.
AB  - Astrocytes protect neurons but also evoke a proinflammatory response to injury
      and viral infections including HIV. We investigated the mechanism of HIV-1
      infection in primary astrocytes, which showed minimal but productive viral
      infection independent of CXCR4. As with ectopic-CD4-expressing astrocytes,
      lysosomotropic agents led to increased HIV-1 infection in wild-type but not Rabs
      5, 7, and 11-ablated astrocytes. Instead, HIV-1 infection was decreased in Rab
      depleted astrocytes, corroborating viral entry by endocytosis. HIV-1 produced
      persistent infection in astrocytes (160 days); no evidence of latent infection
      was seen. Notably, one caveat is that endosomal modifiers enhanced wild-type HIV
      1 infection (M- and T-tropic) in astrocytes, suggesting endocytic entry of the
      virus. Impeding endocytosis by inhibition of Rab 5, 7 or 11 will inhibit HIV
      infection in astrocytes. Although the contribution of such low-level infection in
      astrocytes to neurological complications is unclear, it may serve as an elusive
      viral reservoir in the central nervous system. 

PMID- 24889224
TI  - Comparison of the Oilseed rape mosaic virus and Tobacco mosaic virus movement
      proteins (MP) reveals common and dissimilar MP functions for tobamovirus spread.
AB  - Tobacco mosaic virus (TMV) is a longstanding model for studying virus movement
      and macromolecular transport through plasmodesmata (PD). Its movement protein
      (MP) interacts with cortical microtubule (MT)-associated ER sites (C-MERs) to
      facilitate the formation and transport of ER-associated viral replication
      complexes (VRCs) along the ER-actin network towards PD. To investigate whether
      this movement mechanism might be conserved between tobamoviruses, we compared the
      functions of Oilseed rape mosaic virus (ORMV) MP with those of MP(TMV). We show
      that MP(ORMV) supports TMV movement more efficiently than MP(TMV). Moreover,
      MP(ORMV) localizes to C-MERs like MP(TMV) but accumulates to lower levels and
      does not localize to larger inclusions/VRCs or along MTs, patterns regularly seen
      for MP(TMV). Our findings extend the role of C-MERs in viral cell-to-cell
      transport to a virus commonly used for functional genomics in Arabidopsis.
      Moreover, accumulation of tobamoviral MP in inclusions or along MTs is not
      required for virus movement. 

PMID- 24889225
TI  - Multi-parameter exploration of HIV-1 virus-like particles as neutralizing
      antibody immunogens in guinea pigs, rabbits and macaques.
AB  - Virus-like particles (VLPs) offer a platform to test the hypothesis that, since
      antibody binding to native envelope glycoprotein (Env) trimers results in HIV-1
      neutralization, that native Env trimers presented in membranes may be useful for
      inducing neutralizing antibodies (nAbs) in a vaccine setting. So far, VLPs have
      not fulfilled this potential. Here, using a "shotgun" approach, we evaluated a
      wide cross-section of variables in a series of VLP immunizations. We identified 3
      tentative leads. First, that VLP doses may not have been sufficient for optimal
      nAb induction. Second, that dampening the antigenicity of non-functional Env (for
      example uncleaved gp160) using either protease digests or IgG masking may be
      useful. Third, that guinea pig sera preferentially target non-conserved epitopes
      and exhibit relatively high background activity, suggesting that rabbits may be
      preferable as small animal vaccine models. Recent immunogenicity studies in
      rabbits appear to bear out all 3 of these leads. 

PMID- 24889226
TI  - Capsid protein: evidences about the partial protective role of neutralizing
      antibody-independent immunity against dengue in monkeys.
AB  - The role of cellular immune response in dengue virus infection is not yet fully
      understood. Only few studies in murine models propose that CD8(+) T-cells are
      associated with protection from infection and disease. At the light of recent
      reports about the protective role of CD8(+) T-cells in humans and the no
      correlation between neutralizing antibodies and protection observed in several
      studies, a vaccine based on cell-mediated immunity constitute an attractive
      approach. Our group has developed a capsid-based vaccine as nucleocpasid-like
      particles from dengue-2 virus, which induced a protective CD4(+) and CD8(+) cell
      mediated immunity in mice, without the contribution of neutralizing antibodies.
      Herein we evaluated the immunogenicity and protective efficacy of this molecule
      in monkeys. Neither IgG antibodies against the whole virus nor neutralizing
      antibodies were elicited after the antigen inoculation. However, animals
      developed a cell-mediated immunity, measured by gamma interferon secretion and
      cytotoxic capacity. Although only one out of three vaccinated animals was fully
      protected against viral challenge, a viral load reduction was observed in this
      group compared with the placebo one, suggesting that capsid could be the base on
      an attractive vaccine against dengue. 

PMID- 24889228
TI  - Host cell autophagy promotes BK virus infection.
AB  - Autophagy is important for a variety for virus life cycles. We sought to
      determine the role of autophagy in human BK polyomavirus (BKPyV) infection. The
      addition excess amino acids during viral infection reduced BKPyV infection.
      Perturbing autophagy levels using inhibitors, 3-MA, bafilomycin A1, and spautin
      1, also reduced infection, while rapamycin treatment of host cells increased
      infection. siRNA knockdown of autophagy genes, ATG7 and Beclin-1, corresponded to
      a decrease in BKPyV infection. BKPyV infection not only correlated with
      autophagosome formation, but also virus particles localized to autophagy-specific
      compartments early in infection. These data support a novel role for autophagy in
      the promotion of BKPyV infection. 

PMID- 24889227
TI  - Differential transcription of fathead minnow immune-related genes following
      infection with frog virus 3, an emerging pathogen of ectothermic vertebrates.
AB  - Frog virus 3 (FV3) and other ranaviruses are responsible for die-offs involving
      wild, farmed, and captive amphibians, fish, and reptiles. To ascertain which
      elements of the immune system respond to infection, we explored transcriptional
      responses following infection of fathead minnow cells with either wild type (wt)
      FV3 or a knock out (KO) mutant targeting the 18 kDa immediate early gene (18K).
      At 8h post infection we observed marked upregulation of multiple transcripts
      encoding proteins affecting innate and acquired immunity. Sequences expressed 4
      fold or higher in wt-infected cells included transcripts encoding interferon
      (IFN), IFN regulatory factors (IRFs), IFN stimulated genes (ISGs) such as Mx and
      MHC class I, and interleukins IL-1beta, IL-8, IL-17C and IL-12. Cells infected
      with the 18K KO mutant (?18K) showed qualitative differences and lower levels of
      induction. Collectively, these results indicate that ranavirus infection induced
      expression of multiple cellular genes affecting both innate and acquired
      immunity.

PMID- 24889230
TI  - Initial characterization of vaccinia virus B4 suggests a role in virus spread.
AB  - Currently, little is known about the ankyrin/F-box protein B4. Here, we report
      that B4R-null viruses exhibited reduced plaque size in tissue culture, and
      decreased ability to spread, as assessed by multiple-step growth analysis.
      Electron microscopy indicated that B4R-null viruses still formed mature and
      extracellular virions; however, there was a slight decrease of virions released
      into the media following deletion of B4R. Deletion of B4R did not affect the
      ability of the virus to rearrange actin; however, VACV811, a large vaccinia virus
      deletion mutant missing 55 open reading frames, had decreased ability to produce
      actin tails. Using ectromelia virus, a natural mouse pathogen, we demonstrated
      that virus devoid of EVM154, the B4R homolog, showed decreased spread to organs
      and was attenuated during infection. This initial characterization suggests that
      B4 may play a role in virus spread, and that other unidentified mediators of
      actin tail formation may exist in vaccinia virus. 

PMID- 24889229
TI  - Abrogation of TLR3 inhibition by discrete amino acid changes in the C-terminal
      half of the West Nile virus NS1 protein.
AB  - West Nile virus (WNV) is a mosquito-transmitted pathogen, which causes
      significant disease in humans. The innate immune system is a first-line defense
      against invading microorganism and many flaviviruses, including WNV, have evolved
      multifunctional proteins, which actively suppress its activation and antiviral
      actions. The WNV non-structural protein 1 (NS1) inhibits signal transduction
      originating from Toll-like receptor 3 (TLR3) and also critically contributes to
      virus genome replication. In this study we developed a novel FACS-based screen to
      attempt to separate these two functions. The individual amino acid changes P320S
      and M333V in NS1 restored TLR3 signaling in virus-infected HeLa cells. However,
      virus replication was also attenuated, suggesting that the two functions are not
      easily separated and may be contained within overlapping domains. The residues we
      identified are completely conserved among several mosquito- and tick-borne
      flaviviruses, indicating that they are of biological importance to the virus. 

PMID- 24889231
TI  - Effect of specific amino acid substitutions in the putative fusion peptide of
      structural glycoprotein E2 on Classical Swine Fever Virus replication.
AB  - E2, along with E(rns) and E1, is an envelope glycoprotein of Classical Swine
      Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment,
      host range susceptibility and virulence in natural hosts. Here we evaluate the
      role of a specific E2 region, (818)CPIGWTGVIEC(828), containing a putative fusion
      peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone
      of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how
      individual amino acid substitutions within this region of E2 may affect
      replication of BICv. A synthetic peptide representing the complete E2 FP amino
      acid sequence adopted a beta-type extended conformation in membrane mimetics,
      penetrated into model membranes, and perturbed lipid bilayer integrity in vitro.
      Similar peptides harboring amino acid substitutions adopted comparable
      conformations but exhibited different membrane activities. Therefore, a
      preliminary characterization of the putative FP (818)CPIGWTGVIEC(828) indicates a
      membrane fusion activity and a critical role in virus replication. 

PMID- 24889232
TI  - A chicken influenza virus recognizes fucosylated alpha2,3 sialoglycan receptors
      on the epithelial cells lining upper respiratory tracts of chickens.
AB  - Influenza viruses recognize sialoglycans as receptors. Although viruses isolated
      form chickens preferentially bind to sialic acid alpha2,3 galactose
      (SAalpha2,3Gal) glycans as do those of ducks, chickens were not experimentally
      infected with viruses isolated from ducks. A chicken influenza virus,
      A/chicken/Ibaraki/1/2005 (H5N2) (Ck/IBR) bound to fucose-branched SAalpha2,3Gal
      glycans, whereas the binding towards linear SAalpha2,3Gal glycans was weak. On
      the epithelial cells of the upper respiratory tracts of chickens, fucose-branched
      SAalpha2,3Gal glycans were detected, but not linear SAalpha2,3Gal glycans. The
      growth of Ck/IBR in MDCK-FUT cells, which were genetically prepared to express
      fucose-branched SAalpha2,3Gal glycans, was significantly higher than that in the
      parental MDCK cells. The present results indicate that fucose-branched
      SAalpha2,3Gal glycans existing on the epithelial cells lining the upper
      respiratory tracts of chickens are critical for recognition by Ck/IBR. 

PMID- 24889233
TI  - Mice of the resistant H-2(b) haplotype mount broad CD4(+) T cell responses
      against 9 distinct Friend virus epitopes.
AB  - To date, only a single Friend virus (FV) peptide recognized by CD4(+) T cells in
      FV-infected mice of the resistant H-2(b) haplotype has been described. To more
      thoroughly examine the repertoire of CD4(+) T cell responses in H-2(b) mice
      infected with this retrovirus, 18mer peptides spanning the FV gag, pol, and env
      coding regions with 11mer overlaps were synthesized. The peptides were then used
      to stimulate whole splenocytes and purified CD4(+) T cells from FV-infected mice
      in an IFNgamma ELISPOT assay. Nine new CD4(+) T cell epitopes were identified, 3
      encoded by gag, 1 by pol, and 5 by env. The high resistance of H-2(b) mice could
      be related to this very broad CD4(+) T cell response against multiple peptides
      during FV infection. 

PMID- 24889234
TI  - Vaccinia virus F5 is required for normal plaque morphology in multiple cell lines
      but not replication in culture or virulence in mice.
AB  - Vaccinia virus (VACV) gene F5L was recently identified as a determinant of plaque
      morphology that is truncated in Modified Vaccinia virus Ankara (MVA). Here we
      show that F5L also affects plaque morphology of the virulent VACV strain Western
      Reserve (WR) in some, but not all cell lines, and not via previously described
      mechanisms. Further, despite a reduction in plaque size for VACV WR lacking F5L
      there was no evidence of reduced virus replication or spread in vitro or in vivo.
      In vivo we examined two mouse models, each with more than one dose and measured
      signs of disease and virus burden. These data provide an initial characterization
      of VACV F5L in a virulent strain of VACV. Further they show the necessity of
      testing plaque phenotypes in more than one cell type and provide an example of a
      VACV gene required for normal plaque morphology but not replication and spread. 

PMID- 24889235
TI  - Length quantization of DNA partially expelled from heads of a bacteriophage T3
      mutant.
AB  - DNA packaging of phages phi29, T3 and T7 sometimes produces incompletely packaged
      DNA with quantized lengths, based on gel electrophoretic band formation. We
      discover here a packaging ATPase-free, in vitro model for packaged DNA length
      quantization. We use directed evolution to isolate a five-site T3 point mutant
      that hyper-produces tail-free capsids with mature DNA (heads). Three tail gene
      mutations, but no head gene mutations, are present. A variable-length DNA segment
      leaks from some mutant heads, based on DNase I-protection assay and electron
      microscopy. The protected DNA segment has quantized lengths, based on restriction
      endonuclease analysis: six sharp bands of DNA missing 3.7-12.3% of the last end
      packaged. Native gel electrophoresis confirms quantized DNA expulsion and, after
      removal of external DNA, provides evidence that capsid radius is the quantization
      ruler. Capsid-based DNA length quantization possibly evolved via selection for
      stalling that provides time for feedback control during DNA packaging and
      injection. 

PMID- 24889236
TI  - The delta domain of the HK97 major capsid protein is essential for assembly.
AB  - The 102 residue N-terminal extension of the HK97 major capsid protein, the delta
      domain, is normally present during the assembly of immature HK97 procapsids, but
      it is removed during maturation like well-known internal scaffolding proteins of
      other tailed phages and herpesviruses. The delta domain also shares other unusual
      properties usually found in other viral and phage scaffolding proteins, including
      its location on the inside of the capsid, a high predicted and measured alpha
      helical content, and an additional prediction for the ability to form parallel
      coiled-coils. Viral scaffolding proteins are essential for capsid assembly and
      phage viability, so we tested whether the HK97 delta domain was essential for
      capsid assembly. We studied the effects of deleting all or parts of the delta
      domain on capsid assembly and on complementation of capsid-protein-defective
      phage, and our results demonstrate that the delta domain is required for HK97
      capsid assembly. 

PMID- 24889238
TI  - Temperature-dependent symptom recovery in Nicotiana benthamiana plants infected
      with tomato ringspot virus is associated with reduced translation of viral RNA2
      and requires ARGONAUTE 1.
AB  - Symptom recovery in nepovirus-infected plants has been attributed to the
      induction of RNA silencing. However, recovery is not always accompanied with
      viral RNA clearance. In this study, we show that recovery of Nicotiana
      benthamiana plants infected with the tomato ringspot virus (ToRSV) is associated
      with a reduction of the steady-state levels of RNA2-encoded coat protein (CP) and
      movement protein but not of RNA2. In vivo labeling experiments revealed efficient
      synthesis of the CP early in infection, but reduced RNA2 translation later in
      infection. Silencing of Argonaute1-like (Ago1) genes prevented both symptom
      recovery and RNA2 translation repression. Similarly, growing the plants at lower
      temperature (21  degrees C rather than 27  degrees C) alleviated the recovery and
      the translation repression. Taken together, our results suggest that recovery of
      ToRSV-infected plants is associated with an Ago1-dependent mechanism that
      represses the translation of viral RNA2.

PMID- 24889237
TI  - Enhanced human receptor binding by H5 haemagglutinins.
AB  - Mutant H5N1 influenza viruses have been isolated from humans that have increased
      human receptor avidity. We have compared the receptor binding properties of these
      mutants with those of wild-type viruses, and determined the structures of their
      haemagglutinins in complex with receptor analogues. Mutants from Vietnam bind
      tighter to human receptor by acquiring basic residues near the receptor binding
      site. They bind more weakly to avian receptor because they lack specific
      interactions between Asn-186 and Gln-226. In contrast, a double mutant,
      Delta133/Ile155Thr, isolated in Egypt has greater avidity for human receptor
      while retaining wild-type avidity for avian receptor. Despite these increases in
      human receptor binding, none of the mutants prefers human receptor, unlike
      aerosol transmissible H5N1 viruses. Nevertheless, mutants with high avidity for
      both human and avian receptors may be intermediates in the evolution of H5N1
      viruses that could infect both humans and poultry. 

PMID- 24889239
TI  - The ubiquitin-proteasome system is required for the early stages of porcine
      circovirus type 2 replication.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine
      circovirus-associated diseases (PCVAD). It has been shown that the ubiquitin
      proteasome system (UPS) is correlated with viral infection, but its role in PCV2
      replication remains unknown. In the present study, we explored the interplay
      between PCV2 replication and the UPS in PK15 cells and found that treatment with
      a proteasome inhibitor (MG132 and lactacystin) significantly decreased the PCV2
      titer at the early infection stage. We further revealed that inhibition of the
      UPS did not affect virus entry but decreased viral protein expression and RNA
      transcription potentially in a cell cycle-dependent manner. PCV2 infection has
      little effect on the chymotrypsin-like activity, and the gene-silencing of
      ubiquitin reduced the PCV2 titer, which indicates that the effective replication
      of PCV2 may be related to protein ubiquitination. Taken together, our data
      suggested that PCV2 replication requires the UPS machinery, which may represent a
      potential antiviral target against PCV2. 

PMID- 24889241
TI  - A novel mycovirus closely related to viruses in the genus Alphapartitivirus
      confers hypovirulence in the phytopathogenic fungus Rhizoctonia solani.
AB  - We report here the biological and molecular attributes of a novel dsRNA mycovirus
      designated Rhizoctonia solani partitivirus 2 (RsPV2) from strain GD-11 of R.
      solani AG-1 IA, the causal agent of rice sheath blight. The RsPV2 genome
      comprises two dsRNAs, each possessing a single ORF. Phylogenetic analyses
      indicated that this novel virus species RsPV2 showed a high sequence identity
      with the members of genus Alphapartitivirus in the family Partitiviridae, and
      formed a distinct clade distantly related to the other genera of Partitiviridae.
      Introduction of purified RsPV2 virus particles into protoplasts of a virus-free
      virulent strain GD-118 of R. solani AG-1 IA resulted in a derivative isogenic
      strain GD-118T with reduced mycelial growth and hypovirulence to rice leaves.
      Taken together, it is concluded that RsPV2 is a novel dsRNA virus belonging to
      Alphapartitivirus, with potential role in biological control of R. solani. 

PMID- 24889242
TI  - Adenovirus assembly is impaired by BMI1-related histone deacetylase activity.
AB  - Polycomb ring finger oncogene BMI1 (B cell-specific Moloney murine leukemia virus
      integration site 1) plays a critical role in development of several types of
      cancers. Here, we report an inverse relationship between levels of BMI1
      expression and adenovirus (Ad) progeny production. Enforced BMI1 expression in
      A549 cells impaired Ad progeny production. In contrast, knocking-down of
      endogenous BMI1 expression enhanced progeny production of a conditionally
      replicating Ad and wild-type Ad5 and Ad11p. Ad vectors overexpressing BMI1 were
      not impaired in the replication of progeny genomes and in the expression of E1A
      and Ad structural proteins. However, 293 cells infected by Ad vector
      overexpressing BMI1 contained a large proportion of morphologically irregular Ad
      particles. This effect was reversed in 293 cells pre-treated with the histone
      deacetylase (HDAC) inhibitor trichostatin A (TSA) in parallel with the production
      of infectious Ad particles. Our findings suggest an inhibitory role of BMI1 in Ad
      morphogenesis that can be implied in Ad tropism and Ad-mediated cancer therapy. 

PMID- 24889240
TI  - E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing
      factor.
AB  - Adenovirus inundates the productively infected cell with linear, double-stranded
      DNA and an abundance of single-stranded DNA. The cellular response to this
      stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group
      C adenovirus that fails to express the E1B-55K and E4orf3 genes is unable to
      suppress the DNA-damage response. Cells infected with this double-mutant virus
      display significant morphological heterogeneity at late times of infection and
      frequently contain fragmented nuclei. Nuclear fragmentation was due to the
      translocation of apoptosis inducing factor (AIF) from the mitochondria into the
      nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1
      (PARP-1), which appeared to be activated by viral DNA replication. Nuclear
      fragmentation did not occur in AIF-deficient cells or in cells treated with a
      PARP-1 inhibitor. The E1B-55K or E4orf3 proteins independently prevented nuclear
      fragmentation subsequent to PARP-1 activation, possibly by altering the
      intracellular distribution of PAR-modified proteins. 

PMID- 24889243
TI  - Molecular determinants of dengue virus 2 envelope protein important for virus
      entry in FcgammaRIIA-mediated antibody-dependent enhancement of infection.
AB  - Antibody-dependent enhancement (ADE) of infection may cause severe illness in
      patients suffering a secondary infection by a heterologous dengue virus (DENV)
      serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing
      antibodies form infectious virus-Ab complexes with the newly infecting serotype
      and enhance virus infection by binding to the Fcgamma receptors (FcgammaR) on
      FcgammaR-bearing cells. In this study, we determined that molecular determinants
      of DENV2 envelope protein critical for virus entry during non-ADE infection are
      also required for ADE infection mediated by FcgammaRIIA, and binding of virus-Ab
      complexes with FcgammaRIIA alone is not sufficient for ADE of infection. The
      FcgammaRIIA mainly plays an auxiliary role in concentrating the virus-Ab complex
      to the cell surface, and other primary cellular receptors are required for virus
      entry. Understanding the viral entry pathway in ADE of DENV infection will
      greatly facilitate rational designs of anti-viral therapeutics against severe
      dengue disease associated with ADE. 

PMID- 24889244
TI  - Silencing of neurotropic flavivirus replication in the central nervous system by
      combining multiple microRNA target insertions in two distinct viral genome
      regions.
AB  - In recent years, microRNA-targeting has become an effective strategy for
      selective control of tissue-tropism and pathogenesis of both DNA and RNA viruses.
      Here, using a neurotropic flavivirus as a model, we demonstrate that simultaneous
      miRNA targeting of the viral genome in the open reading frame and 3'-noncoding
      regions for brain-expressed miRNAs had an additive effect and produced a more
      potent attenuation of the virus compared to separate targeting of those regions.
      Multiple miRNA co-targeting of these two distantly located regions completely
      abolished the virus neurotropism as no viral replication was detected in the
      developing brain of neonatal mice. Furthermore, no viral antigens were detected
      in neurons, and neuronal integrity in the brain of mice was well preserved. This
      miRNA co-targeting approach can be adapted for other viruses in order to minimize
      their replication in a cell- or tissue-type specific manner, but most
      importantly, to prevent virus escape from miRNA-mediated silencing. 

PMID- 24889247
TI  - Factors that affect the intracellular localization and trafficking of African
      horse sickness virus core protein, VP7.
AB  - African horse sickness virus (AHSV) VP7 is the major core protein of the virion.
      Apart from its role in virus assembly, VP7 forms crystalline-like particles
      during infection and when expressed in insect cells. The aim of this study was to
      investigate the process of VP7 crystalline-like particle formation. The
      intracellular distribution of VP7 was characterized in different systems and the
      association of VP7 with virus factories during AHSV infection was investigated.
      It was shown that the majority of VP7 is sequestered into these particles, and is
      therefore not available for new virion assembly. This is likely to have a
      negative impact on virus assembly and yield. By using specific markers and
      inhibitors of host trafficking pathways, VP7 localization was shown to be
      independent of host trafficking mechanisms and evaded host defenses against
      aggregation. Studying the process of VP7 crystalline-like particle formation will
      help us further understand AHSV replication and assembly. 

PMID- 24889245
TI  - IL-17 contributes to neutrophil recruitment but not to control of viral
      replication during acute mouse adenovirus type 1 respiratory infection.
AB  - IL-17-producing CD4(+) helper T cells (Th17 cells) promote inflammatory responses
      to many pathogens. We used mouse adenovirus type 1 (MAV-1) to determine
      contributions of IL-17 to adenovirus pathogenesis. MAV-1 infection of C57BL/6
      mice upregulated lung expression of IL-17 and the Th17-associated factors IL-23
      and RORgammat. Only CD4(+)T cells were associated with virus-specific IL-17
      production. Fewer neutrophils were recruited to airways of IL-17(-/-) mice
      following MAV-1 infection, but there were no other differences in pulmonary
      inflammation between IL-17(+/+) and IL-17(-/-) mice. Mice depleted of neutrophils
      using anti-Gr-1 antibody had greater lung viral loads than controls. Despite
      impaired neutrophil recruitment, there were no differences between IL-17(+/+) and
      IL-17(-/-) mice in peak lung viral loads, clearance of virus from the lungs, or
      establishment of protective immunity. We demonstrate robust Th17 responses during
      MAV-1 respiratory infection, but these responses are not essential for control of
      virus infection or for virus-induced pulmonary inflammation. 

PMID- 24889248
TI  - Coat protein mutations in an attenuated Cucumber mosaic virus encoding mutant 2b
      protein that lacks RNA silencing suppressor activity induces chlorosis with
      photosynthesis gene repression and chloroplast abnormalities in infected tobacco
      plants.
AB  - In tobacco plants, the Cucumber mosaic virus (CMV) pepo strain induces mosaic
      symptoms, including pale green chlorosis and malformed tissues. Here, we
      characterized the involvement of 2b protein and coat protein (CP) in the
      development of mosaic symptoms. A 2b mutant (R46C) that lacks viral suppressor of
      RNA silencing (VSR) activity showed an asymptomatic phenotype with low levels of
      virus accumulation. Tomato spotted wilt virus NSs protein did not complement the
      virulence of the R46C, although it did restore high-level virus accumulation.
      However, R46C mutants expressing mutated CP in which the amino acid P129 was
      mutated to A, E, C, Q, or S induced chlorosis that was associated with reduced
      expression of chloroplast and photosynthesis related genes (CPRGs) and abnormal
      chloroplasts with fewer thylakoid membranes. These results suggest that the CP of
      the CMV pepo strain acquires virulence by amino acid mutations, which causes CPRG
      repression and chloroplast abnormalities. 

PMID- 24889246
TI  - The crucial role of bile acids in the entry of porcine enteric calicivirus.
AB  - Replication of porcine enteric calicivirus (PEC) in LLC-PK cells is dependent on
      the presence of bile acids in the medium. However, the mechanism of bile acid
      dependent PEC replication is unknown. Understanding of bile acid-mediated PEC
      replication may provide insight into cultivating related human noroviruses,
      currently uncultivable, which are the major cause of viral gastroenteritis
      outbreaks in humans. Our results demonstrated that while uptake of PEC into the
      endosomes does not require bile acids, the presence of bile acids is critical for
      viral escape from the endosomes into cell cytoplasm to initiate viral
      replication. We also demonstrated that bile acid transporters including the
      sodium-taurocholate co-transporting polypeptide and the apical sodium-dependent
      bile acid transporter are important in exerting the effects of bile acids in PEC
      replication in cells. In summary, our results suggest that bile acids play a
      critical role in virus entry for successful replication. 

PMID- 24889249
TI  - Human pegivirus (GB virus C) NS3 protease activity inhibits induction of the type
      I interferon response and is not inhibited by HCV NS3 protease inhibitors.
AB  - We previously found that human pegivirus (HPgV; formerly GBV-C) NS3 protease
      activity inhibits Human Immunodeficiency Virus (HIV) replication in a CD4+ T cell
      line. Given the protease's similarity to the Hepatitis C virus (HCV) NS3
      protease, we characterized HPgV protease activity and asked whether it affects
      the type I interferon response or is inhibited by HCV protease antagonists. We
      characterized the activity of proteases with mutations in the catalytic triad and
      demonstrated that the HCV protease inhibitors Telaprevir, Boceprevir, and
      Danoprevir do not affect HPgV protease activity. HPgV NS3 protease cleaved MAVS
      but not TRIF, and it inhibited interferon responses sufficiently to enhance
      growth of an interferon-sensitive virus. Therefore, HPgV's inhibition of the
      interferon response could help promote HPgV persistence, which is associated with
      clinical benefits in HIV-infected patients. Our results also imply that HCV
      protease inhibitors should not interfere with the beneficial effects of HPgV in
      HPgV/HCV/HIV infected patients. 

PMID- 24889250
TI  - Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers
      drug resistance and partly compensates for replication deficits.
AB  - We investigated the origin and the effect of insertion D67D-THGERDLGPA within HIV
      1 RT from a patient failing antiviral therapy. The insertion developed within the
      context of pre-existing NRTI and NNRTI mutations (M41L, L210W, T215Y and N348I).
      Concurrently, the NRTI mutations T69I and V118I and the NNRTI mutations K103N and
      Y181C were detected for the first time. High-level drug resistance (fold
      changes>=50) and a good replication capacity (87% of wild-type) were observed,
      significantly higher than for the previous virus without insertion. The insertion
      was very similar to a region within human chromosome 17 (31/34 nucleotide
      identity), and had already been detected independently in a Japanese HIV-1
      isolate. These results suggest that a particular sequence within human chromosome
      17 is prone to horizontal gene transfer into the HIV-1 RT finger subdomain. This
      insertion confers selective advantage to HIV-1 by its contribution to multi-drug
      resistance and restoration of impaired replication capacity. 

PMID- 24889251
TI  - Pseudorabies viral replication is inhibited by a novel target of miR-21.
AB  - The pseudorabies virus (PRV) is a porcine virus classified as a member of the
      Alphaherpesvirinae subfamily of Herpesviridae. Recent studies have confirmed that
      viruses regulate the gene expression in host cells. Commonly affected genes
      include oxidative-stress response genes, genes involved in the
      phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) signaling pathway, and
      interferon- and interleukin-related genes. However, the post-transcriptional
      regulation of host genes following PRV infection is hitherto unclear. In this
      study, we used miRNA microarray approaches to assess miRNA expression in PRV
      infected porcine kidney 15 cell line (PK-15), and observed that miR-21 was
      expressed at high level 12h after the cells were infected with PRV. Furthermore,
      we identified chemokine (C-X-C motif) ligand 10 (CXCL10), also named interferon
      gamma inducible protein-10 (IP-10), as a novel target gene of miR-21. IP-10 was
      down-regulated at 4h after PRV infection. PRV replication was significantly
      inhibited by IP-10 overexpression. 

PMID- 24889252
TI  - A new look at adenovirus splicing.
AB  - Adenovirus type 2 RNA splicing events were quantitatively mapped by using deep
      cDNA sequencing. The majority of the previously identified splice sites were
      detected. The lack of complete consistency between the present and previous
      results is because of some sites which were incorrectly mapped in previous
      studies, such as the splice sites for pVII, pVIII and E3-11.6K. Several
      previously predicted splice sites such as that for E3-14.5K and E4ORF3/4 were not
      detected. In addition, several new splice sites were identified. The novel RNAs
      may code for hitherto undetected proteins or alternatively spliced mRNAs for
      known proteins. The open reading frames downstream of two novel splice sites,
      located in the major late transcription unit region, were shown to be highly
      conserved. Another interesting possibility is that some of them are non-coding
      RNAs. Finally, the adenovirus mRNA polyadenylation sites were accurately mapped
      and in some cases shown to be heterogeneous. 

PMID- 24889254
TI  - Perpetuation and reassortment of gull influenza A viruses in Atlantic North
      America.
AB  - Gulls are important hosts of avian influenza A viruses (AIVs) and gull AIVs often
      contain gene segments of mixed geographic and host lineage origins. In this
      study, the prevalence of AIV in gulls of Newfoundland, Canada from 2008 to 2011
      was analyzed. Overall prevalence was low (30/1645, 1.8%) but there was a distinct
      peak of infection in the fall. AIV seroprevalence was high in Newfoundland gulls,
      with 50% of sampled gulls showing evidence of previous infection. Sequences of 16
      gull AIVs were determined and analyzed to shed light on the transmission,
      reassortment and persistence dynamics of gull AIVs in Atlantic North America.
      Intercontinental and waterfowl lineage reassortment was prevalent. Of particular
      note were a wholly Eurasian AIV and another with an intercontinental reassortant
      waterfowl lineage virus. These patterns of geographic and inter-host group
      transmission highlight the importance of characterization of gull AIVs as part of
      attempts to understand global AIV dynamics. 

PMID- 24889253
TI  - Parvovirus particles and movement in the cellular cytoplasm and effects of the
      cytoskeleton.
AB  - Cell infection by parvoviruses requires that capsids be delivered from outside
      the cell to the cytoplasm, followed by genome trafficking to the nucleus. Here we
      microinject capsids into cells that lack receptors and followed their movements
      within the cell over time. In general the capsids remained close to the positions
      where they were injected, and most particles did not move to the vicinity of or
      enter the nucleus. When 70 kDa-dextran was injected along with the capsids that
      did not enter the nucleus in significant amounts. Capsids conjugated to peptides
      containing the SV40 large T-antigen nuclear localization signal remained in the
      cytoplasm, although bovine serum albumen conjugated to the same peptide entered
      the nucleus rapidly. No effects of disruption of microfilaments, intermediate
      filaments, or microtubules on the distribution of the capsids were observed.
      These results suggest that movement of intact capsids within cells is primarily
      associated with passive processes.

PMID- 24889255
TI  - Parvovirus B19 VLP recognizes globoside in supported lipid bilayers.
AB  - Studies have suggested that the glycosphingolipid globoside (Gb4Cer) is a
      receptor for human parvovirus B19. Virus-like particles bind to Gb4Cer on thin
      layer chromatograms, but a direct interaction between the virus and lipid
      membrane-associated Gb4Cer has been debated. Here, we characterized the binding
      of parvovirus B19 VP1/VP2 virus-like particles to glycosphingolipids (i) on thin
      layer chromatograms (TLCs) and (ii) incorporated into supported lipid bilayers
      (SLBs) acting as cell-membrane mimics. The binding specificities of parvovirus
      B19 determined in the two systems were in good agreement; the VLP recognized both
      Gb4Cer and the Forssman glycosphingolipid on TLCs and in SLBs compatible with the
      role of Gb4Cer as a receptor for this virus. 

PMID- 24889256
TI  - Asymmetric stereodivergent strategy towards aminocyclitols.
AB  - A concise asymmetric synthesis of aminocyclitols, such as diastereomeric 2
      deoxystreptamine analogues and conduramine A, is described. The Pd-catalyzed
      asymmetric desymmetrization of meso 1,4-dibenzolate enables the synthesis of
      highly oxidized cyclohexane architectures. These scaffolds can potentially be
      used to access new aminoglycoside antibiotics and enantiomerically pure alpha
      glucosidase inhibitors.

PMID- 24889257
TI  - Synthesis of the first radiolabeled 188Re N-heterocyclic carbene complex and
      initial studies on its potential use in radiopharmaceutical applications.
AB  - A novel approach towards the synthesis of radiolabeled organometallic rhenium
      complexes is presented. We successfully synthesized and analyzed the first
      (188)Re-labeled N-heterocyclic biscarbene complex, trans-dioxobis(1,1'-methylene
      bis(3,3'-diisopropylimidazolium-2-ylidene))(188)rhenium(V) hexafluorophosphate
      ((188)Re-4) via transmetalation using an air-stable and moisture-stable silver(I)
      biscarbene complex. In order to assess the viability of this complex as a
      potential lead structure for in vivo applications, the stability of the (188)Re
      NHC complex was tested in physiologically relevant media. Ultimately, our studies
      illustrate that the complex we synthesized dissociates rapidly and is therefore
      unsuitable for use in radiopharmaceuticals. However, it is clear that the
      transmetalation approach we have developed is a rapid, robust, and mild method
      for the synthesis of new (188)Re-labeled carbene complexes.

PMID- 24889258
TI  - Oral budesonide as a therapy for protein-losing enteropathy in children after the
      Fontan operation.
AB  - BACKGROUND AND AIM: Protein-losing enteropathy is a rare complication of the
      Fontan palliation surgery. Budesonide is an effective treatment option for
      protein-losing enteropathy. We reviewed our retrospective experience in four
      patients who were treated with oral budesonide. METHODS: Four patients with
      refractory protein-losing enteropathy after the Fontan operation were started on
      oral budesonide 9 mg/daily. After achieving normal serum albumin the dose was
      tapered to 3 mg. Response to oral budesonide, side effects, and serum albumin
      levels before the treatment and at first, fourth, and ninth months of the
      budesonide course were recorded. Efficacy was measured based on serum albumin
      levels and clinical symptoms. RESULTS: Mean pretherapy albumin was 2.25 g/dL
      (range 1.7 to 2.5 g/dL) and nine months after therapy it was 4.15 g/dL (range 3.9
      to 4.4 g/dL) (p < 0.05). All patients had at least a transient improvement in
      serum albumin levels and clinical findings. Systemic side effects included
      cushingoid features and oral moniliasis. All patients had improvement in side
      effects after tapering budesonide to 3 mg. The treatment was terminated in one
      case as soon as serum albumin level exceeded 3 g/dL. One death occurred from
      respiratory arrest six months after budesonide discontinuation. CONCLUSION:
      Budesonide can be used to treat protein-losing enteropathy in selected patients
      with cardiac diseases.

PMID- 24889260
TI  - Reply 1.

PMID- 24889259
TI  - Poloxamine/fibrin hybrid hydrogels for non-viral gene delivery.
AB  - Hydrogels have been widely investigated for localized, sustained gene delivery
      because of the similarity of their physical properties to native extracellular
      matrix and their ability to be formed under mild conditions amenable to the
      incorporation of bioactive molecules. The objective of this study was to develop
      bioactive hydrogels composed of macromolecules capable of enhancing the
      efficiency of non-viral vectors. Hybrid hydrogels were prepared by simultaneous
      enzymatic and Michael-type addition crosslinking of reduced fibrinogen and an
      acrylated amphiphilic block copolymer, Tetronic T904, in the presence of
      dithiothreitol (DTT) and thrombin. T904/fibrin hydrogels degraded by surface
      erosion in the presence of plasmin and provided sustained release of polyplex
      vectors up to an order of magnitude longer than pure fibrin gel control. In
      addition, the rate of gel degradation and time-course of polyplex vector release
      were readily controlled by varying the T904/fibrinogen ratio in the gel
      composition. When added to transfected neuroblastoma (N2A) cells, both native
      T904 itself and hydrogel degradation products significantly increased polyplex
      transfection efficiency with minimal effect on cell viability. To evaluate gel
      based transfection, N2A cells encapsulated in small fibrin clusters were covered
      by or suspended within polyplex-loaded hydrogels. Cells progressively degraded
      and invaded the hybrid hydrogels, exhibiting increasing gene expression over 2
      weeks and then diminishing but persistent gene expression for over 1 month. In
      conclusion, these results demonstrate that T904/fibrin hybrid hydrogels can be
      promising tissue engineering scaffolds that provide local, controlled release of
      non-viral vectors in combination with the generation of bioactive gel degradation
      products that actively enhance vector efficiency. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 24889263
TI  - Substrate profiling of glutathione S-transferase with engineered enzymes and
      matched glutathione analogues.
AB  - The identification of specific substrates of glutathione S-transferases (GSTs) is
      important for understanding drug metabolism. A method termed bioorthogonal
      identification of GST substrates (BIGS) was developed, in which a reduced
      glutathione (GSH) analogue was developed for recognition by a rationally
      engineered GST to label the substrates of the corresponding native GST. A K44G
      W40A-R41A mutant (GST-KWR) of the mu-class glutathione S-transferases GSTM1 was
      shown to be active with a clickable GSH analogue (GSH-R1) as the cosubstrate. The
      GSH-R1 conjugation products can react with an azido-based biotin probe for ready
      enrichment and MS identification. Proof-of-principle studies were carried to
      detect the products of GSH-R1 conjugation to 1-chloro-2,4-dinitrobenzene (CDNB)
      and dopamine quinone. The BIGS technology was then used to identify GSTM1
      substrates in the Chinese herbal medicine Ganmaocongji. 

PMID- 24889261
TI  - Aging in the context of cohort evolution and mortality selection.
AB  - This study examines historical patterns of aging through the perspectives of
      cohort evolution and mortality selection, where the former emphasizes the
      correlation across cohorts in the age dependence of mortality rates, and the
      latter emphasizes cohort change in the acceleration of mortality over the life
      course. In the analysis of historical cohort mortality data, I find support for
      both perspectives. The rate of demographic aging, or the rate at which mortality
      accelerates past age 70, is not fixed across cohorts; rather, it is affected by
      the extent of mortality selection at young and late ages. This causes later
      cohorts to have higher rates of demographic aging than earlier cohorts. The rate
      of biological aging, approximating the rate of the senescence process,
      significantly declined between the mid- and late-nineteenth century birth cohorts
      and stabilized afterward. Unlike the rate of demographic aging, the rate of
      biological aging is not affected by mortality selection earlier in the life
      course but rather by cross-cohort changes in young-age mortality, which cause
      lower rates of biological aging in old age among later cohorts. These findings
      enrich theories of cohort evolution and have implications for the study of limits
      on the human lifespan and evolution of aging. 

PMID- 24889262
TI  - The expression and functional role of a FOXC1 related mRNA-lncRNA pair in oral
      squamous cell carcinoma.
AB  - The Fork head box C1 (FOXC1) gene is overexpressed in multiple malignant tumors
      and is functionally correlated with tumor progression. However, its' role in oral
      squamous cell carcinoma (OSCC) is still unclear. Recent studies have revealed
      that many long non-coding RNA (lncRNAs) cooperate with adjacent coding genes and
      form a functional "lncRNA-mRNA pair". In this study, we report a new lncRNA FOXC1
      upstream transcript (FOXCUT) that was remarkably overexpressed in 23 OSCC
      patients, as was the adjacent FOXC1 gene. The expressions of FOXC1 and FOXCUT
      were positively correlated. When the expression of FOXCUT was down-regulated by
      small interfering RNA (siRNA), the expression of FOXC1 was also decreased.
      Moreover, in OSCC cells Tca8113 and SCC-9, down-regulation of either FOXC1 or
      FOXCUT by siRNA could inhibit cell proliferation and cell migration in vitro and
      was accompanied with a reduction of MMP2, MMP7, MMP9, and VEGF-A. In conclusion,
      FOXC1 may be co-amplified with FOXCUT in OSCC, and both of them may be
      functionally involved in the tumor progression of OSCC. This provides evidence
      that both FOXC1 and FOXCUT may serve as novel biomarkers and therapeutic targets
      in OSCC patients who overexpress this "lncRNA-mRNA pair". 

PMID- 24889264
TI  - A systematic review of observational studies evaluating implant placement in the
      maxillary jaws of medically compromised patients.
AB  - BACKGROUND: Even though the efficacy of implant treatment and the excellent
      success rates that modern implant surfaces yield remain unchallenged, there is
      limited information available on implant success rates in medically compromised
      patients. PURPOSE: The aim of this systematic review was to evaluate the survival
      of implants placed in the maxillary jaws of medically compromised patients.
      MATERIALS AND METHODS: Two reviewers using predefined selection criteria
      performed an electronic search complemented by a manual search, independently and
      in duplicate. RESULTS: After the final selection, 11 studies reporting on four
      distinct medical conditions were included out of 405 potentially eligible titles.
      In detail, three studies reported on implants placed in diabetic patients, six on
      implants placed in patients with a history of oral cancer, one on implants in
      patients with a history of epilepsy, and one on implants in patients with
      autoimmune rheumatoid arthritis. CONCLUSIONS: Placement of maxillary implants in
      medically compromised patients seems to yield acceptable survival rates. Implant
      survival in well-controlled diabetic patients, patients diagnosed with rheumatoid
      arthritis, and patients treated for severe epilepsy is comparable to that in
      healthy patients. Implants placed in the maxillae of patients treated for oral
      cancer may attain osseointegration less predictably than in the mandible.

PMID- 24889265
TI  - Discussion of combining biomarkers to optimize patient treatment recommendations.
AB  - Kang, Janes and Huang propose an interesting boosting method to combine
      biomarkers for treatment selection. The method requires modeling the treatment
      effects using markers. We discuss an alternative method, outcome weighted
      learning. This method sidesteps the need for modeling the outcomes, and thus can
      be more robust to model misspecification. 

PMID- 24889266
TI  - Au nanomatryoshkas as efficient near-infrared photothermal transducers for cancer
      treatment: benchmarking against nanoshells.
AB  - Au nanoparticles with plasmon resonances in the near-infrared (NIR) region of the
      spectrum efficiently convert light into heat, a property useful for the
      photothermal ablation of cancerous tumors subsequent to nanoparticle uptake at
      the tumor site. A critical aspect of this process is nanoparticle size, which
      influences both tumor uptake and photothermal efficiency. Here, we report a
      direct comparative study of ~90 nm diameter Au nanomatryoshkas (Au/SiO2/Au) and
      ~150 nm diameter Au nanoshells for photothermal therapeutic efficacy in highly
      aggressive triple negative breast cancer (TNBC) tumors in mice. Au
      nanomatryoshkas are strong light absorbers with 77% absorption efficiency, while
      the nanoshells are weaker absorbers with only 15% absorption efficiency. After an
      intravenous injection of Au nanomatryoshkas followed by a single NIR laser dose
      of 2 W/cm(2) for 5 min, 83% of the TNBC tumor-bearing mice appeared healthy and
      tumor free >60 days later, while only 33% of mice treated with nanoshells
      survived the same period. The smaller size and larger absorption cross section of
      Au nanomatryoshkas combine to make this nanoparticle more effective than Au
      nanoshells for photothermal cancer therapy. 

PMID- 24889267
TI  - Love withdrawal predicts electrocortical responses to emotional faces with
      performance feedback: a follow-up and extension.
AB  - BACKGROUND: Parental use of love withdrawal is thought to affect children's later
      psychological functioning because it creates a link between children's
      performance and relational consequences. In addition, recent studies have begun
      to show that experiences of love withdrawal also relate to the neural processing
      of socio-emotional information relevant to a performance-relational consequence
      link, and can moderate effects of oxytocin on social information processing and
      behavior. The current study follows-up on our previous results by attempting to
      confirm and extend previous findings indicating that experiences of maternal love
      withdrawal are related to electrocortical responses to emotional faces presented
      with performance feedback. RESULTS: More maternal love withdrawal was related to
      enhanced early processing of facial feedback stimuli (reflected in more positive
      VPP amplitudes, and confirming previous findings). However, attentional
      engagement with and processing of the stimuli at a later stage were diminished in
      those reporting higher maternal love withdrawal (reflected in less positive LPP
      amplitudes, and diverging from previous findings). CONCLUSIONS: Maternal love
      withdrawal affects the processing of emotional faces presented with performance
      feedback differently in different stages of neural processing.

PMID- 24889269
TI  - Cognitive-emotional hyperarousal in the offspring of parents vulnerable to
      insomnia: a nuclear family study.
AB  - Cognitive-emotional hyperarousal is believed to be a predisposing factor for
      insomnia; however, there is limited information on the association of familial
      vulnerability to insomnia and cognitive-emotional hyperarousal. The aim of this
      study was to estimate the heritability of stress-related insomnia and examine
      whether parental vulnerability to stress-related insomnia is associated with
      cognitive-emotional hyperarousal in their offspring. We studied a volunteer
      sample of 135 nuclear families comprised of 270 middle-aged (51.5 +/- 5.4 years)
      fathers and mothers and one of their biological offspring (n = 135, 20.2 +/- 1.1
      years). We measured vulnerability to stress-related insomnia (i.e. Ford Insomnia
      Response to Stress Test: FIRST), perceived stress, depression and anxiety in all
      participants, and arousability, presleep cognitive and somatic arousal, coping
      and personality in the offspring. We found a heritability estimate of 29% for
      FIRST scores. High FIRST parents had three to seven times the odds of having
      offspring highly vulnerable to stress-related insomnia. Offspring of high FIRST
      parents showed higher arousability, presleep cognitive arousal and emotion
      oriented coping. Furthermore, high FIRST mothers contributed to offspring's
      higher anxiety and lower task-oriented coping, while high FIRST fathers
      contributed to offspring's higher presleep somatic arousal and conscientiousness.
      Vulnerability to stress-related insomnia is significantly heritable. Parents
      vulnerable to stress-related insomnia have offspring with cognitive-emotional
      hyperarousal who rely upon emotion-oriented coping. These data give support to
      the notion that arousability and maladaptive coping are key factors in the
      aetiology of insomnia.

PMID- 24889268
TI  - High throughput quantitative reverse transcription PCR assays revealing over
      expression of cancer testis antigen genes in multiple myeloma stem cell-like side
      population cells.
AB  - Multiple myeloma (MM) stem cells, proposed to be responsible for the
      tumourigenesis, drug resistance and recurrence of this disease, are enriched in
      the cancer stem cell-like side population (SP). Cancer testis antigens (CTA) are
      attractive targets for immunotherapy because they are widely expressed in cancers
      but only in limited types of normal tissues. We designed a high throughput assay,
      which allowed simultaneous relative quantifying expression of 90 CTA genes
      associated with MM. In the three MM cell lines tested, six CTA genes were over
      expressed in two and LUZP4 and ODF1 were universally up-regulated in all three
      cell lines. Subsequent study of primary bone marrow (BM) from eight MM patients
      and four healthy donors revealed that 19 CTA genes were up-regulated in SP of MM
      compared with mature plasma cells. In contrast, only two CTA genes showed a
      moderate increase in SP cells of healthy BM. Furthermore, knockdown using small
      interfering RNA (siRNA) revealed that LUZP4 expression is required for colony
      forming ability and drug resistance in MM cells. Our findings indicate that
      multiple CTA have unique expression profiles in MM SP, suggesting that CTA may
      serve as targets for immunotherapy that it specific for MM stem cells and which
      may lead to the long-term cure of MM. 

PMID- 24889270
TI  - Severe refractory autoimmune hemolytic anemia with five-year complete hematologic
      response to third course of treatment with rituximab: a case report.
AB  - INTRODUCTION: Rituximab is an emerging treatment for autoimmune hemolytic anemia.
      We report the case of a patient with a five-year complete hematologic response to
      a third course of treatment with rituximab. Cases of response to rituximab re
      treatments have been reported, but none to our knowledge that failed multiple
      prior treatments and achieved as durable a response. CASE PRESENTATION: A 45-year
      old Hispanic man presented at age 26 with darkening urine and cold intolerance.
      His blood tests revealed elevated lactic dehydrogenase and bilirubin, a
      hemoglobin level of 7.4g/dL, and a positive Coombs test for complement C3 and
      immunoglobulin G antibody. A diagnosis of autoimmune hemolytic anemia was made.
      After failing multiple therapies including prednisone, splenectomy,
      immunoglobulin, cyclosporine, danocrine and azathioprine, our patient was treated
      with a four-week course of rituximab at a dose of 375mg/m2 weekly, 10 years
      following initial presentation. He achieved a rapid and complete hematologic
      response that lasted 25 months. Re-treatment with the same course of rituximab
      prompted a second response that lasted 18 months. A third re-treatment has
      achieved an ongoing five-year complete hematologic response. CONCLUSIONS: This is
      an unusual case of a durable five-year remission of autoimmune hemolytic anemia
      with rituximab re-treatment following relapse after two prior courses of
      rituximab and despite the persistence of immunoglobulin G and complement-coated
      red blood cells. No mechanistic explanations for improved response to rituximab
      re-treatment in autoimmune hemolytic anemia have been reported in the literature.
      Future studies of rituximab or other B cell-targeting antibodies in the treatment
      of autoimmune hemolytic anemia should explore autoantibody immunoglobulin G
      subclass switching and alterations in complement inhibitory proteins on red blood
      cell membranes as potential correlates of hematologic response.

PMID- 24889271
TI  - The peri-procedural use of dabigatran in patients undergoing left atrial ablation
      for atrial fibrillation.
AB  - INTRODUCTION: Pulmonary vein isolation is an effective strategy in patients with
      atrial fibrillation (AF). The peri-procedural use of anticoagulation is routinely
      employed to reduce thromboembolic risk. AIMS/METHODS: The aim of this study was
      to compare the use of Dabigatran to the other 2 strategies involving the use of
      Warfarin. Single centre observational study comparing 3 anticoagulation
      strategies: Group 1 consisted of patients maintained on Warfarin (5.15 +/- 2.52
      mg) with a therapeutic INR of 2-3. Group 2 comprised patients initially treated
      with Warfarin (6.98 +/- 3.17 mg), which was discontinued 1 week prior to LA
      ablation, during which time patients were bridged with a therapeutic dose of
      Dalteparin. Group 3 included patients anticoagulated with Dabigatran (40 patients
      received 150 mg BID, 3 patients received 110 mg BID), which was discontinued 24
      30 h prior to the procedure. RESULTS: A total of 207 patients were included in
      the study. There were no significant differences in age, sex, LA volume, CHADS2
      score or proportion of patients with persistent AF. There were no significant
      differences in the number of patients with intra-cardiac thrombus found at TOE
      (Group 1: 2.3% vs. Group 2: 1.5% vs. Group 3: 0%; P = 0.37). Furthermore, there
      were no differences in the rate of groin hematoma (2.2% vs. 1.5% vs. 2.3%; P =
      0.8) or the development of pericardial effusion (5.4% vs. 8.8% vs. 2.3%; P =
      0.54). No thromboembolic events were seen. CONCLUSION: Peri-procedural use of
      Dabigatran during AF ablation procedures is safe, with no significant difference
      when compared to conventional anticoagulation with either Warfarin bridged with
      Dalteparin or uninterrupted Warfarin.

PMID- 24889272
TI  - Mamillo-accessory notch and foramen: distribution patterns and correlation with
      superior lumbar facet structure.
AB  - The mamillary (MP) and the accessory (AP) processes are two important anatomical
      landmarks in the lumbar vertebral morphology. These two processes form the
      mamillo-accessory notch (MAN) between them. In the living, the MP and the AP are
      connected together by the mamillo-accessory ligament (MAL). The medial branches
      of lumbar dorsal rami pass underneath the MAL. The MAL often undergoes varied
      degrees of ossification with diverse notching at the junction of these two
      processes, often with formation of a discrete foramen (MAF). Reports on the
      distribution of these notches (MAN) and foramina (MAF) are very few and most of
      them do not discuss such ossification in context of morphology of adjoining
      structures in the vertebrae. Lumbar vertebral and sacral specimens were screened
      for three different categories of narrowing at the mamillo-accessory junction:
      firstly >1/2 notch, secondly 3/4 notch, and thirdly MAF and their distribution
      patterns were mapped along the lumbar spine. Transverse dimensions of superior
      facet articulating surfaces [length (a)] and widths of MPs [length (b)] were
      recorded. Relative widths of the MPs were calculated as index M (a/b). Results
      suggest associations between the degrees of assimilation of the MPs into the
      facet joints, the index M values, and the different types of mamillo-accessory
      junctional anatomy. This study may help to understand if MAN and MAF related
      dorsal rami entrapment neuropathies arise merely due to osteoarthritic
      ossification of the MAL or could also be accounted for by facet dimensions or
      degree of MP-facet fusions that abut close to the mamillo-accessory junctions. 

PMID- 24889273
TI  - Post-operative benefits of Tisseel((r))/Tissucol ((r)) for mesh fixation in
      patients undergoing Lichtenstein inguinal hernia repair: secondary results from
      the TIMELI trial.
AB  - PURPOSE: The Tisseel/Tissucol for mesh fixation in Lichtenstein hernia repair
      (TIMELI) study showed that mesh fixation with human fibrin sealant during
      inguinal hernia repair significantly reduced moderate-severe complications of
      pain 12 months post-operatively compared with sutures. Further analyses may
      assist surgeons by investigating predictors of post-surgical complications and
      identifying patients that may benefit from Tisseel/Tissucol intervention.
      METHODS: Univariate and multivariate analyses identified risk factors for
      combined pain, numbness and groin discomfort (PND) visual analogue scale (VAS)
      score 12 months post-operatively. Variables tested were: fixation method, age,
      employment status, physical activity, nerve handling, PND VAS score at pre
      operative visit and 1 week post-operatively. The effect of fixation technique on
      separate PND outcomes 12 months post-surgery was also assessed. Analyses included
      the intention-to-treat (ITT) population and a subpopulation with pre-operative
      PND VAS > 30 mm. RESULTS: 316 patients were included in the ITT, with 130
      patients in the subpopulation with pre-operative PND VAS > 30. Multivariate
      analysis identified mesh fixation with sutures, worsening pre-operative PND and
      worsening PND 1 week post-surgery as significant predictors of 12-month PND in
      the ITT population; mesh fixation with sutures was a significant predictor of 12
      month PND in the pre-operative PND VAS > 30 subpopulation (p < 0.05). Mesh
      fixation with Tisseel/Tissucol resulted in significantly less numbness and a
      lower intensity of groin discomfort compared with sutures at 12 months; there was
      no difference in pain between the treatment groups. CONCLUSIONS: Pre-operative
      discomfort may be an important predictor of post-operative pain, numbness and
      discomfort. Tisseel/Tissucol may improve long-term morbidity over conventional
      sutures in these patients.

PMID- 24889274
TI  - Neonatal laparoscopic inguinal hernia repair: a 3-year experience.
AB  - PURPOSE: To retrospectively analyze the feasibility, safety and complication rate
      of laparoscopic inguinal herniorraphy in babies weighing 5 kg or less. METHODS:
      Thirty infants weighing 5 kg or less underwent laparoscopic inguinal hernia
      repair during a 3-year period. Twenty-eight infants were born preterm and the
      mean body weight at surgery was 3,800 kg. Internal inguinal ring was closed with
      a non-absorbable purse-string suture. Contralateral processus vaginalis was
      closed if patent. Feeding was started on the same day and the patient discharged
      the following day. Follow-up consisted of physical examination at 1 week, 6 and
      12 months post-operatively. RESULTS: Of the 30 patients (27 males, 3 females), 11
      had bilateral and 19 monolateral hernia (16 right, 3 left). At laparoscopy, 23
      infants needed to have bilateral herniorraphies. The mean corrected gestational
      age at surgery was 49.1 weeks. The mean operative time for repair was 30 min for
      unilateral and 41 min for bilateral hernia. There were not intra- or post
      operative complications as well as conversions or recurrences. CONCLUSIONS:
      Laparoscopic inguinal hernia repair in newborns and in ex-preterm infants is a
      safe and effective procedure to perform and, perhaps, even less technically
      demanding than open herniotomy.

PMID- 24889276
TI  - Formation of a "pseudosuitane"-type complex between a triptycene-derived
      bis(crown ether) host and 1,1'-(anthracene-9,10-diyl)bis(N-benzylmethanaminium):
      a new method for the synthesis of linear polyrotaxanes.
AB  - A "pseudosuitane"-type complex between a triptycene-derived bis(crown ether) host
      and 1,1'-(anthracene-9,10-diyl)bis(N-benzylmethanaminium) can be formed in the
      solution and the solid state, which provides us a new method for the synthesis of
      linear polyrotaxanes. 

PMID- 24889275
TI  - Usefulness and safety of oral cryotherapy in the prevention of oral mucositis
      after conditioning regimens with high-dose melphalan for autologous stem cell
      transplantation for lymphoma and myeloma.
AB  - BACKGROUND: Oral mucositis (OM) is a common complication of conditioning regimens
      with high-dose melphalan (HDmel). This retrospective cohort study analyzes the
      impact of oral cryotherapy (OC) or room temperature saline rinses on the
      prevention of OM in patients with multiple myeloma (MM) or lymphoid neoplasias
      submitted to autologous stem cell transplantation (ASCT) in a single center.
      PATIENTS AND METHODS: From August 2006 to July 2011, 134 consecutive patients
      were enrolled. Two consecutive groups were included: Non-OC (August 2006 to April
      2009, 68 patients) and OC (May 2009 to July 2011, 66 cases). MM cases (78, 58%)
      received HDmel as the conditioning regimen and 56 patients (42%) with lymphoma
      received BEAM. RESULTS: The non-OC and OC groups were comparable for the main
      clinicobiologic features and type of neoplasia. OM was more frequent and severe
      in patients receiving BEAM as the conditioning therapy. The group of OC showed
      less frequent and less severe mucositis and fewer days on antibiotics. No
      differences were observed in the duration of OM, need for parenteral nutrition
      and narcotics, and the length of hospital stay on comparison with the OC and non
      OC groups. By multivariate analyses, OC was an independent favorable prognostic
      factor for OM development. CONCLUSIONS: This study shows that OC is more
      effective than saline rinses in the prevention of OM in patients with lymphoma
      and myeloma receiving conditioning regimens with HDmel for ASCT.

PMID- 24889278
TI  - High current densities enable exoelectrogens to outcompete aerobic heterotrophs
      for substrate.
AB  - In mixed-culture microbial fuel cells (MFCs), exoelectrogens and other
      microorganisms compete for substrate. It has previously been assumed that
      substrate losses to other terminal electron acceptors over a fed-batch cycle,
      such as dissolved oxygen, are constant. However, a constant rate of substrate
      loss would only explain small increases in coulombic efficiencies (CEs, the
      fraction of substrate recovered as electrical current) with shorter cycle times,
      but not the large increases in CE that are usually observed with higher current
      densities and reduced cycle times. To better understand changes in CEs, COD
      concentrations were measured over time in fed-batch, single-chamber, air-cathode
      MFCs at different current densities (external resistances). COD degradation rates
      were all found to be first-order with respect to COD concentration, even under
      open circuit conditions with no current generation (first-order rate constant of
      0.14 +/- 0.01 h(-1) ). The rate of COD removal increased when there was current
      generation, with the highest rate constant (0.33 +/- 0.02 h(-1) ) obtained at the
      lowest external resistance (100 Omega). Therefore, as the substrate concentration
      was reduced more quickly due to current generation, the rate of loss of substrate
      to non-exoelectrogens decreased due to this first-order substrate-concentration
      dependence. As a result, coulombic efficiencies rapidly increased due to
      decreased, and not constant, removal rates of substrate by non-exoelectrogens.
      These results show that higher current densities (lower resistances) redirect a
      greater percentage of substrate into current generation, enabling large increase
      in CEs with increased current densities. Biotechnol. Bioeng. 2014;111: 2163-2169.
      (c) 2014 Wiley Periodicals, Inc. 

PMID- 24889277
TI  - Past and present of hepatitis E in the Netherlands.
AB  - BACKGROUND: Recent studies show that endemic hepatitis E virus (HEV) infection
      occurs frequently in some developed countries. In the Netherlands in 2013, the
      routine screening of 35,220 plasma donations for HEV RNA showed 20 donors to be
      viremic (1:1761), which seems to contradict reports of declining HEV
      seroprevalence in the recent past. STUDY DESIGN AND METHODS: To asses HEV
      infection pressure changes over time, archived samples from Dutch blood donations
      collected in 1988 and 2000 were tested for anti-HEV immunoglobulin (Ig)G. The
      findings were compared to the HEV seroprevalence among donors in 2011. RESULTS:
      The age-adjusted prevalence of anti-HEV IgG for Dutch donors aged 18 to 64
      declined from 46.6% in 1988 to 27.3% in 2000 and to 20.9% in 2011. The reduction
      of seroprevalence was apparent for all age groups between 1988 and 2000, and for
      donors older than 40 between 2000 and 2011, but the seroprevalence among donors
      aged 18 to 29 increased between 2000 and 2011. Recent changes in HEV infection
      pressure are more apparent in the youngest donors, who to a lesser extent reflect
      cumulative exposure to HEV in the past. Donors aged 18 to 21 showed decreasing
      HEV seroprevalence from 19.8% in 1988 to 7.0% in 1995 and to 4.3% in 2000,
      followed by an increase to 12.7% in 2011. CONCLUSION: HEV antibody patterns in
      young and old Dutch donors, in 1988 to 2011, suggest that decades ago, HEV was
      ubiquitous and most persons acquired infection. Subsequently HEV incidence was
      low during a prolonged period, to increase again in recent years.

PMID- 24889279
TI  - Achieving low-density lipoprotein cholesterol treatment goals among dyslipidemic
      individuals in the Levant: the CEntralized Pan-Levant survey on tHE
      Undertreatment of hypercholeSterolemia (CEPHEUS) study.
AB  - BACKGROUND: Several studies that evaluated achieving lipid goals have
      demonstrated an undertreatment of dyslipidemia. We evaluated the use and efficacy
      of lipid-lowering agents (LLAs) in reducing low-density lipoprotein cholesterol
      (LDL-C) to recommended levels in the Levant region. DESIGN AND METHODS: A multi
      center, cross-sectional survey enrolled 1002 dyslipidemic patients (August 2010 -
      January 2011) on LLAs for >=3 months. Collection of data and blood samples was
      done over one visit. Physicians and patients filled out questionnaires pertaining
      to dyslipidemia diagnosis and treatment. LDL-C target levels were defined
      according to international guidelines. RESULTS: The full analysis set included
      992 patients. Mean age was 58.0 +/- 11.6 years (41% women, 65.7% diabetics and
      51.5% had history of coronary heart disease). LLAs were prescribed for primary
      prevention or secondary prevention or familial hypercholesterolemia in 45.8% and
      52.8% and 1.4% of patients; respectively. Overall, 64.0% and 56.8% of the
      patients attained their LDL-C goal recommended by the NCEP ATP III and TJETF
      guidelines, respectively. According to the 2004 NCEP ATP III updated guidelines,
      about 24.8% of the very high risk group attained their LDL goal of <=70 mg/dL.
      Smoking, diabetes, metabolic syndrome, history of cardiovascular disease,
      increased waist circumference, and elevated pre-treatment LDL-C level were all
      associated with not reaching LDL-C goals. CONCLUSIONS: Although the study cohort
      was a relatively high risk group and might not be representative of the general
      population, we found that about 60% of enrolled individuals achieved the LDL-C
      treatment goals and 24.8% of the very high risk group achieved the recommended
      LDL-C targets of <=70 mg/dl; national strategies and aggressive awareness
      campaigns to effectively control lipid levels to recommended target levels,
      especially in the high risk groups, are urgently needed.

PMID- 24889280
TI  - Impact of socio-economic factors on the long-term effectiveness of
      antihypertensive treatment with an angiotensin II receptor blocker: an
      observational study.
AB  - OBJECTIVE: To investigate the role of socio-economic factors on the therapeutic
      effectiveness of and therapeutic adherence to the angiotensin II receptor blocker
      (ARB) olmesartan (OM) alone or in combination with hydrochlorothiazide in the
      treatment of arterial hypertension. RESEARCH DESIGN AND METHODS: In a multi
      center, open-label, prospective and long-term observational study, data from
      hypertensive patients treated with OM were analyzed at baseline, month 3 and
      month 12 within the context of patients' socio-economic status (SES), determined
      using pre-defined criteria by physicians in outpatient practices and including
      multivariate analysis. RESULTS: Overall, 7724 patients were assigned to three
      subgroups representing low, medium and high socio-economic status. Baseline
      conditions differed significantly between the subgroups. Patients of low SES had
      worse nutritional habits, less physical activity and more concomitant medication
      compared to patients of high SES. Cardiovascular risk factors were more common in
      the low SES group as were concomitant diseases such as heart failure, coronary
      heart disease, atherosclerosis and renal failure. OM therapy led to a significant
      decrease in blood pressure (23.0/11.6 mmHg) in all patients. The blood pressure
      target of <140/90 mmHg was achieved in about 70% of the documented population.
      Effectiveness was comparable between patients with low, medium or high SES.
      Treatment adherence was high in the overall population with only minor
      differences between the subgroups. In total the incidence of adverse events (AEs)
      was 1.6% documented in 98 patents (1.3%) during the course of the study. Of this
      total number only 1.0% was related to the drug, matching the percentage expressed
      in the Summary of Product Characteristics (SmPC). CONCLUSIONS: The ARB OM is
      effective and well tolerated in all patients, irrespective of their socio
      economic status. The risk status and the established cardiovascular disease of
      hypertensive patients are strongly influenced by the SES. To validate these
      interesting data a randomized controlled trial is needed.

PMID- 24889281
TI  - Testing versus guessing blood glucose values: impact on self-care behaviors in
      type 2 diabetes.
AB  - OBJECTIVE: To assess differences between estimated blood glucose values and those
      measured on a blood glucose meter and the impact on self-care behavior in type 2
      diabetes. RESEARCH DESIGN AND METHODS: Subjects >=18 years with type 2 diabetes
      (N = 297) attending a Taking Control of Your Diabetes conference were asked
      questions about diabetes management and to estimate their current blood glucose.
      Study staff tested subjects' blood glucose on a meter. After seeing the result,
      subjects were again asked questions on diabetes management. CLINICAL TRIAL
      REGISTRATION: NCT01453413. MAIN OUTCOME MEASURE: The percentage of subject blood
      glucose estimations that were outside ISO 15197:2003 accuracy criteria (>+/-15
      mg/dL or >+/-20% of meter glucose values). RESULTS: Nearly half (46%) of subjects
      estimated blood glucose values outside ISO 15197:2003 accuracy criteria. Time
      since last blood glucose test, time since last meal, testing frequency, and A1C
      did not have an effect on differences between estimated blood glucose values and
      meter results. In the questionnaire before blood glucose testing, most subjects
      strongly agreed, agreed, or neither agreed nor disagreed that 'I make decisions
      about my diabetes, such as my food intake or my insulin dose even when I do not
      test my blood sugar' (71%) and 'My body tells me without testing if my blood
      sugar is low or high' (77%). After blood glucose testing, 99% of subjects
      strongly agreed, agreed, or neither agreed nor disagreed that 'Knowing my blood
      sugar by checking could help me make different diabetes decisions'. CONCLUSIONS:
      Self-monitoring of blood glucose is an important component of diabetes self
      management. Testing rather than guessing blood glucose values is important to
      obtain accurate results and inform people with type 2 diabetes to make effective,
      appropriate diabetes management decisions. A potential limitation of this study
      is that the subject population may not be representative of the general
      population of people with diabetes; however, the conference setting may attract a
      more motivated population, which could underestimate the magnitude of the
      results.

PMID- 24889282
TI  - Lipid attainment among patients newly treated with lipid-altering drugs.
AB  - OBJECTIVE: Guidelines for preventing and treating patients with coronary artery
      disease have traditionally focused on reducing low-density lipoprotein
      cholesterol (LDL-C). Current treatments are effective; however, previous studies
      have identified a significant proportion of patients that are not achieving the
      recommended lipid levels. New guidelines were introduced November 2013. The
      objective of this study was to examine recent practice patterns and factors
      related to initiating treatment for hypercholesterolemia, which provides a
      comparative baseline to the introduction of new guidelines. RESEARCH DESIGN AND
      METHODS: We conducted a retrospective cohort analysis utilizing laboratory
      results of lipid profiles and medical claims from January 2007 to September 2011
      to identify patients with elevated LDL-C and diagnoses of hypercholesterolemia
      without prior pharmacotherapy. Pharmacotherapy dispensed, treatment
      modifications, LDL-C-goal attainment, and potential drug intolerance were
      evaluated. RESULTS: Overall, among newly treated patients, 70.9% achieved the
      recommended LDL-C level within the first year of treatment; however, only 19.4%
      of those with coronary heart disease (CHD) or CHD risk equivalents achieved the
      more aggressive LDL-C goal of <70 mg/dL (1.8 mmol/L). LDL-C goals were generally
      achieved with the use of statins; however, a majority of patients underwent
      treatment modification(s) (e.g., discontinuation or restart). More than half of
      the patients diagnosed with elevated LDL-C did not initiate pharmacotherapy.
      LIMITATIONS: Data was unavailable for inpatient hospitalizations, family history
      of cardiovascular diseases, body weight, and height, and likely under-reporting
      of smoking within claims data. CONCLUSIONS: Newly treated patients with elevated
      LDL-C results generally achieved the recommended and risk-specific LDL-C goal
      with the use of lipid-altering drugs; however, there still exists a notable
      population of patients with CHD or CHD risk equivalents who were not treated to
      goal and a significant number of patients who do not receive lipid-lowering
      pharmacotherapy. New therapies and prescribing practices are warranted to
      adequately address these two patient populations.

PMID- 24889283
TI  - Cochlear implant complications in 403 patients: comparative study of adults and
      children and review of the literature.
AB  - OBJECTIVES: The purpose of this study was to assess the postoperative
      complications related to cochlear implants and to discuss the differences
      observed between adult and paediatric populations. Cochlear implant complications
      were defined as any pathological events observed during the postoperative period,
      whether or not they were directly related to the surgical technique. We therefore
      recorded all complications, in the broad sense of the term, ranging from acute
      otitis media to cochlear explantation. STUDY DESIGN: Retrospective analysis of
      cochlear implant patients. MATERIAL AND METHODS: All surgical procedures
      (unilateral or bilateral cochlear implantation, revision surgery) performed in
      our institution between March 1993 and January 2013 were reviewed. This
      population comprised 168 adults (median age at the time of implantation: 51.9
      years), and 235 children (median age at the time of implantation: 4.5 years). All
      postoperative complications were classified as either major (requiring surgical
      revision or hospital management) or minor (requiring conservative management).
      RESULTS: The global complication rate was 19.9% (80/403 cases), comprising 5% of
      major complications (20 cases) and 14.9% of minor complications (60 cases). This
      complication rate was significantly higher in the adult population (P=0.004).
      CONCLUSION: Cochlear implantation is a safe hearing rehabilitation surgical
      technique associated with a low complication rate. However, surgeons must be
      familiar with these complications in order to ensure optimal prevention. Minor
      complications were mainly infectious in children (acute otitis media) and
      cochleovestibular in adults (tinnitus and vertigo). Major complications were
      mostly reimplantation following revision surgery or device failure. Only the
      minor complication rate was significantly higher in the adult population.

PMID- 24889285
TI  - Does the aboveground herbivore assemblage influence soil bacterial community
      composition and richness in subalpine grasslands?
AB  - Grassland ecosystems support large communities of aboveground herbivores that are
      known to directly and indirectly affect belowground properties such as the
      microbial community composition, richness, or biomass. Even though multiple
      species of functionally different herbivores coexist in grassland ecosystems,
      most studies have only considered the impact of a single group, i.e., large
      ungulates (mostly domestic livestock) on microbial communities. Thus, we
      investigated how the exclusion of four groups of functionally different
      herbivores affects bacterial community composition, richness, and biomass in two
      vegetation types with different grazing histories. We progressively excluded
      large, medium, and small mammals as well as invertebrate herbivores using
      exclosures at 18 subalpine grassland sites (9 per vegetation type). We assessed
      the bacterial community composition using terminal restriction fragment length
      polymorphism (T-RFLP) at each site and exclosure type during three consecutive
      growing seasons (2009-2011) for rhizosphere and mineral soil separately. In
      addition, we determined microbial biomass carbon (MBC), root biomass, plant
      carbon:nitrogen ratio, soil temperature, and soil moisture. Even though several
      of these variables were affected by herbivore exclusion and vegetation type,
      against our expectations, bacterial community composition, richness, or MBC were
      not. Yet, bacterial communities strongly differed between the three growing
      seasons as well as to some extent between our study sites. Thus, our study
      indicates that the spatiotemporal variability in soil microclimate has much
      stronger effects on the soil bacterial communities than the grazing regime or the
      composition of the vegetation in this high-elevation ecosystem. 

PMID- 24889286
TI  - Short-term precipitation exclusion alters microbial responses to soil moisture in
      a wet tropical forest.
AB  - Many wet tropical forests, which contain a quarter of global terrestrial biomass
      carbon stocks, will experience changes in precipitation regime over the next
      century. Soil microbial responses to altered rainfall are likely to be an
      important feedback on ecosystem carbon cycling, but the ecological mechanisms
      underpinning these responses are poorly understood. We examined how reduced
      rainfall affected soil microbial abundance, activity, and community composition
      using a 6-month precipitation exclusion experiment at La Selva Biological
      Station, Costa Rica. Thereafter, we addressed the persistent effects of field
      moisture treatments by exposing soils to a controlled soil moisture gradient in
      the lab for 4 weeks. In the field, compositional and functional responses to
      reduced rainfall were dependent on initial conditions, consistent with a large
      degree of spatial heterogeneity in tropical forests. However, the precipitation
      manipulation significantly altered microbial functional responses to soil
      moisture. Communities with prior drought exposure exhibited higher respiration
      rates per unit microbial biomass under all conditions and respired significantly
      more CO2 than control soils at low soil moisture. These functional patterns
      suggest that changes in microbial physiology may drive positive feedbacks to
      rising atmospheric CO2 concentrations if wet tropical forests experience longer
      or more intense dry seasons in the future. 

PMID- 24889287
TI  - Bacterial distribution along a 50  degrees C temperature gradient reveals a
      parceled out hot spring environment.
AB  - Understanding the distribution of bacteria is a major goal of microbial ecology
      which remains to be fully deciphered. In this study, a model 50  degrees C
      temperature gradient at a Northern Thailand hot spring was analyzed to determine
      how the bacterial communities were structured in the environment. Communities
      were examined through 16S rRNA gene amplification, denaturing gradient gel
      electrophoresis, and sequencing. The two major phyla, Cyanobacteria and
      Chloroflexi, showed characteristic distributions along the temperature gradient.
      Different clades were allocated at specific portions of the gradient. Comparisons
      of the bacterial communities along the temperature gradient showed sharp
      decreases of similarity at increasing temperature difference. Peaks of maximum
      richness were observed at 50 and 70  degrees C. This study contributes to explain
      how environmental conditions and microbial interactions can influence the
      distribution of specific bacterial clades and phyla shaping the structure of
      microbial communities in nature.

PMID- 24889288
TI  - Metabolic characteristics of a glycogen-accumulating organism in Defluviicoccus
      cluster II revealed by comparative genomics.
AB  - Glycogen-accumulating organisms (GAOs) may compete with phosphate-accumulating
      organisms (PAOs) for short-chain fatty acids (VFAs) in anaerobic
      polyhydroxyalkanoates (PHA) synthesis, but no consequently aerobic polyphosphate
      accumulation in enhanced biological phosphorus removal (EBPR) process, thus
      deteriorating the EBPR process. They are detected frequently in the deteriorated
      EBPR process, but their metabolisms are still far from our comprehensions for
      there is seldom pure culture. In this study, a nearly complete draft genome of a
      GAOs in Defluviicoccus cluster II, GAO-HK, is recruited from the metagenome of
      activated sludge in a full-scale industrial anoxic/aerobic wastewater plant.
      Comparative genomics reveal similar metabolisms of PHA and glycogen in GAOs of
      GAO-HK, Defluviicoccus tetraformis TFO71 (TFO71) and Competibacter phosphatis
      clade IIA (CPIIA), and PAOs of Accumulibacter clade IIA UW-1 (UW-1) and
      Tetrasphaera elongata Lp2 (Lp2). Although there are similar gene cassettes
      related with polyphosphate metabolism in these GAOs and PAOs, especially for
      Defluviicoccus-relative bacteria and UW-1, ppk1 in GAOs are diverse from those in
      the identified PAOs, implying the difference of polyphosphate metabolism in GAOs
      and PAOs. Additionally, genes related to the dissimilatory denitrification are
      absent in TFO71 and GAO-HK, implying that additional nitrate or nitrite may favor
      PAOs over Defluviicoccus-relative GAOs. Therefore, PAOs suffering from
      competition of Defluviicoccus-relative GAOs might be rescued with the additional
      nitrate/nitrite, which is important to improve the stability of EBPR processes. 

PMID- 24889289
TI  - The development and initial validation of a questionnaire to measure help-seeking
      behaviour in patients with new onset rheumatoid arthritis.
AB  - BACKGROUND: Early treatment for rheumatoid arthritis (RA) is vital. However,
      people often delay in seeking help at symptom onset. An assessment of the reasons
      behind patient delay is necessary to develop interventions to promote rapid
      consultation. OBJECTIVE: Using a mixed methods design, we aimed to develop and
      test a questionnaire to assess the barriers to help seeking at RA onset. DESIGN:
      Questionnaire items were extracted from previous qualitative studies. Fifteen
      people with a lived experience of arthritis participated in focus groups to
      enhance the questionnaire's face validity. The questionnaire was also reviewed by
      groups of multidisciplinary health-care professionals. A test-retest survey of 41
      patients with newly presenting RA or unclassified arthritis assessed the
      questionnaire items' intraclass correlations. RESULTS: During focus groups,
      participants rephrased questions, added questions and deleted items not relevant
      to the questionnaire's aims. Participants organized items into themes: early
      symptom experience, initial reactions to symptoms, self-management behaviours,
      causal beliefs, involvement of significant others, pre-diagnosis knowledge about
      RA, direct barriers to seeking help and relationship with GP. The test-retest
      survey identified seven items (out of 79) with low intraclass correlations which
      were removed from the final questionnaire. CONCLUSION: The involvement of people
      with a lived experience of arthritis and multidisciplinary health-care
      professionals in the preliminary validation of the DELAY (delays in evaluating
      arthritis early) questionnaire has enriched its development. Preliminary
      assessment established its reliability. The DELAY questionnaire provides a tool
      for researchers to evaluate individual, cultural and health service barriers to
      help-seeking behaviour at RA onset.

PMID- 24889290
TI  - Platelet-derived growth factor BB and DD and angiopoietin1 are altered in
      follicular fluid from polycystic ovary syndrome patients.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology
      among women of reproductive age, and is characterized by abnormalities in ovarian
      angiogenesis, among other features. Consistent with this association, follicular
      fluid (FF) concentration and ovarian expression of vascular endothelial growth
      factor (VEGF) are increased in PCOS patients. In this study, we examined the
      protein levels of platelet-derived growth factor (PDGF) BB and DD (PDGFBB and
      PDGFDD), angiopoietin 1 and 2 (ANGPT1 and ANGPT2), and their soluble receptor
      sTIE2 in FF from PCOS and control patients undergoing assisted reproductive
      techniques. We also analyzed the effect of FF from PCOS and control patients on
      tight and adherens junction protein expression in an endothelial cell line.
      PDGFBB and PDGFDD were significantly lower whereas ANGPT1 concentration was
      significantly higher in FF from PCOS patients than from control patients. No
      changes were found in the concentration of ANGPT2 or sTIE2. Expression of claudin
      5 was significantly increased in endothelial cells incubated for 24 hr in the
      presence of FF from PCOS versus from control patients, while vascular-endothelial
      cadherin, beta-catenin, and zonula occludens 1 expression were unchanged. The
      changes observed in the levels of PDGF isoforms and ANGPT1 may prevent VEGF
      induced vascular permeability in the PCOS ovary by regulating endothelial-cell
      junction protein levels. Restoring the levels of angiogenic factors may provide
      new insights into PCOS treatment and the prevention of ovarian hyperstimulation
      syndrome in affected women.

PMID- 24889291
TI  - Response.

PMID- 24889292
TI  - [Quo vadis venereology?].

PMID- 24889293
TI  - Sexually transmitted infections.
AB  - In no other medical field former rare infections of the 1980(th) and 1990(th)
      occur again as this is seen in the field of venerology which is as well based on
      the mobility of the population. Increasing rates of infections in Europe, and
      increasing bacteriological resistances face health professionals with new
      challenges. The WHO estimates more than 340 million cases of illnesses worldwide
      every year. Diseases caused by sexually transmitted infections (STI) in a strict
      sense are syphilis, gonorrhea, lymphogranuloma venereum, granuloma inguinale, and
      chancroid. In a wider sense, all illnesses are included which can mainly be
      transmitted through sexual contact. The term "sexual contact" has to be seen
      widely, from close physical contact to all variants of sexual behavior. This CME
      article is an overview of the most common occurring sexually transmitted
      infections in clinical practice. Both, basic knowledge as well as recent
      developments are discussed below.

PMID- 24889295
TI  - Occupational skin cancer due to UV-irradiation--Analyses of notified cases as
      "virtually-certain" occupational disease in Germany between 2005 and 2011.
AB  - BACKGROUND: UV-induced skin cancer is not yet included in the German ordinance on
      occupational diseases and can only be notified and recognized acknowledged as
      "virtually-certain" occupational disease. The objective of the study was to
      analyze notified and acknowledged cases of occupational skin cancer due to UV
      irradiation in Germany between 2005 and 2011. PATIENTS AND METHODS: All notified
      cases of occupational skin cancer due to UV-irradiation have been analyzed which
      have been registered by the German Statutory accident insurance as of May 2012
      were analyzed. The data analyze was descriptive stratified annually for
      presenting time trends.Data analysis was descriptive, stratified by year to
      defect time trends. RESULTS: Notified cases have increased annually with a total
      of 548 registered cases of occupational skin cancer induced by UV-irradiation
      between 2005 and 2011, and 74 recognized acknowledged cases. In 56 cases the
      procedure was not yet finished. Squamous cell carcinoma (SCC) and in-situ
      squamous cell carcinoma (actinic keratosis, Bowen's disease) were most frequent
      and have been the most frequentlyobserved in 333 notified cases. and between 15.6
      % and 24.9 % have been recognizedof cases with SCC and actinic keratosis were
      recognized, respectively. 184 patients with basal cell carcinoma were notified
      but only 6.5 % recognized acknowledged and only 3 cases with exclusive basal cell
      carcinoma. Out of 50 notified patients with Mmelanoma only one was
      recognizedacknowledged. CONCLUSIONS: The results are in good agreement with the
      proposal of the German Minister of labor to establish UV-induced skin cancer as a
      new occupational disease.

PMID- 24889298
TI  - Hematologic disorders in the occupational dermatologic assessment exemplified by
      UV-induced epithelial skin cancer and B-CLL.

PMID- 24889302
TI  - Porcelain-yellow papule in an 8-year-old girl.

PMID- 24889284
TI  - Bacterial community assemblages associated with the phyllosphere, dermosphere,
      and rhizosphere of tree species of the Atlantic forest are host taxon dependent.
AB  - Bacterial communities associated with tree canopies have been shown to be
      specific to their plant hosts, suggesting that plant species-specific traits may
      drive the selection of microbial species that comprise their microbiomes. To
      further examine the degree to which the plant taxa drive the assemblage of
      bacterial communities in specific plant microenvironments, we evaluated bacterial
      community structures associated with the phyllosphere, dermosphere, and
      rhizosphere of seven tree species representing three orders, four families and
      four genera of plants from a pristine Dense Ombrophilous Atlantic forest in
      Brazil, using a combination of PCR-DGGE of 16S rRNA genes and clone library
      sequencing. Results indicated that each plant species selected for distinct
      bacterial communities in the phyllosphere, dermosphere, and rhizosphere, and that
      the bacterial community structures are significantly related to the plant taxa,
      at the species, family, and order levels. Further characterization of the
      bacterial communities of the phyllosphere and dermosphere of the tree species
      showed that they were inhabited predominantly by species of Gammaproteobacteria,
      mostly related to Pseudomonas. In contrast, the rhizosphere bacterial communities
      showed greater species richness and evenness, and higher frequencies of
      Alphaproteobacteria and Acidobacteria Gp1. With individual tree species each
      selecting for their specific microbiomes, these findings greatly increase our
      estimates of the bacterial species richness in tropical forests and provoke
      questions concerning the ecological functions of the microbial communities that
      exist on different plant parts. 

PMID- 24889304
TI  - Asymptomatic brown patches in a 13-year-old boy.

PMID- 24889306
TI  - Psoriasis predisposition and occupational triggering factors in the appraisal of
      occupational medical expertises.
AB  - BACKGROUND: Psoriasis is an immune-mediated disease with a genetic background.
      Local psoriatic changes can be triggered by exogenous mechanical or irritant
      factors. Causative occupational factors have to be distinguished from the
      spontaneous course of psoriasis in occupational medical evaluations. The
      objective of this work is to demonstrate the medico-legal grounds for a
      homogenous assessment. PATIENTS AND METHODS: The presented recommendations were
      developed in a working group for Occupational and Environmental Dermatology (ABD)
      and the German contact dermatitis group (DKG) of the German Dermatologic Society
      (DDG) based on the German medico-legal framework. RESULTS: Causality between the
      insured activity and the appearance of psoriasis is a prerequisite for the
      recognition of the occupational nature of the disease. This is the case if the
      occupational activity is the exclusive or a legally essential contributing factor
      either for first manifestation or aggravation of the disease. A connection must
      be denied if everyday events are sufficient to trigger the psoriasis. From 1995
      to 2010, 130 cases of psoriasis have been recognized as occupationally related by
      the German statutory accident insurance. CONCLUSIONS: The appraisal of psoriatic
      disease in the occupational medical evaluation is subject to the case assessment
      of the expert witness. In this position paper we present recommendations for a
      homologous basis for diagnosis, causality assessment, estimation of reduction in
      earning capacity and rehabilitation of occupational psoriasis.

PMID- 24889312
TI  - Making tenofovir accessible in the brazilian public health system: patent
      conflicts and generic production.
AB  - In May 2011, the Brazilian Ministry of Health announced the distribution of the
      first batch of locally produced generic tenofovir disoproxil fumarate (TDF) to
      support its program of universal and free access for the treatment of HIV/AIDS.
      The inclusion of TDF in the public health program illustrates what has been
      considered the 'Brazilian model' of HIV/AIDS response, as it illustrates the
      current phase of the Brazilian pharmaceutical economy. Brazil is known for having
      managed to control the expansion of HIV/AIDS through a unique initiative
      combining the public health and the industrial production of generics. But, if at
      first local manufacturers could freely copy ARVs and produce cheaper generic
      versions that were delivered to the Ministry of Health, since the country started
      to grant patents on drugs in 1996, the sustainability of this policy has been
      challenged by the high cost of patented second-line HIV/AIDS treatments. In order
      to assure continuity of the local production of ARVs, and keep the program of
      public health alive, Brazilians are now forced to deal with conflicts of drugs'
      intellectual property rights in order to open the path to generic production.
      This article aims to describe the experiences surrounding TDF in Brazil and the
      unprecedented conflicts and challenges it has brought for our different
      interviewees. Blurring the frontier between the public and the private, the TDF
      case was driven at the same time by an ethic of drug access and regulation of
      drug quality, which has inspired Brazilians to intervene and transform the world
      they live in. 

PMID- 24889310
TI  - Psoriasis predisposition and occupational triggering factors in the appraisal of
      occupational medical expertises.

PMID- 24889313
TI  - Identification of biomarkers for endometriosis in plasma from patients with
      endometriosis using a proteomics approach.
AB  - The present study aimed to examine potential biomarkers for the diagnosis of
      endometriosis. A plasma-based proteomic approach, including 2-dimentional
      electrophoresis and mass spectrometry, was used. Samples were obtained from
      patients with (n=15) and without (n=15) endometriosis, or from mice with
      surgically induced endometriosis. Seven spots corresponding to six differentially
      expressed proteins were identified in the human plasma samples. However, only
      haptoglobin (Hp) was identified to be significantly decreased in the plasma
      levels of patients with endometriosis (P<0.05) and in mice with surgically
      induced endometriosis (P<0.05). The results demonstrated that Hp was
      downregulated in females with endometriosis, and it therefore, may be a useful
      diagnostic tool as a biomarker of endometriosis. 

PMID- 24889314
TI  - Transcriptional and translational control through the 5'-leader region of the
      dmpR master regulatory gene of phenol metabolism.
AB  - Expression of pathways for dissimilation of toxic aromatic compounds such as
      (methyl)phenols interfaces both stress-response and carbon catabolite repression
      control cascades. In Pseudomonas putida, carbon catabolite repression is mediated
      by the protein Crc - a translational repressor that counteracts utilization of
      less-preferred carbon sources as growth substrates until they are needed. In this
      work we dissect the regulatory role of the 5'-leader region (5'-LR) of the dmpR
      gene that encodes the master regulator of (methyl)phenol catabolism. Using
      deletion and substitution mutants combined with artificial manipulations of Crc
      availability in P. putida, we present evidence that a DNA motif within the 5'
      leader region is critical for inhibition of the output from the Pr promoter that
      drives transcription of dmpR, while the RNA chaperone Hfq facilitates Crc
      mediated translation repression through the 5'-leader region of the dmpR mRNA.
      The results are discussed in the light of a model in which Hfq assists Crc to
      target a sequence within a loop formed by secondary structure of the 5'-LR mRNA.
      Our results support the idea that Crc functions as a global translational
      inhibitor to co-ordinate hierarchical carbon utilization in Pseudomonads. 

PMID- 24889315
TI  - Similar diversity-disturbance responses to different physical impacts: three
      cases of small-scale biodiversity increase in the Belgian part of the North Sea.
AB  - Human activities at sea are still increasing. As biodiversity is a central topic
      in the management of our seas, it is important to understand how diversity
      responds to different disturbances related with physical impacts. We investigated
      the effects of three impacts, i.e. sand extraction, dredge disposal and offshore
      wind energy exploitation, on the soft-bottom macrobenthic assemblages in the
      Belgian part of the North Sea. We found similar diversity-disturbance responses,
      mainly related to the fact that different impacts caused similar environmental
      changes. We observed a sediment refinement which triggered a shift towards a
      heterogenic, dynamic (transitional) soft-bottom macrobenthic assemblage, with
      several species typically associated with muddy sands. This led to a local
      unexpected biodiversity increase in the impacted area. On a wider regional scale,
      the ever increasing human impacts might lead to a homogenization of the sediment,
      resulting in a more uniform, yet less diverse benthic ecosystem. 

PMID- 24889316
TI  - Conservation management options and actions: putative decline of coral cover at
      Palmyra Atoll, Northern Line Islands, as a case study.
AB  - Localised loss of live coral cover at Palmyra Atoll (central Pacific Ocean) has
      been attributed to increased temperature and/or sedimentation arising from
      alterations made to the lagoon system. It has been hypothesised that a causeway
      spanning the lagoon hinders water circulation, resulting in warmer and/or more
      turbid water flowing towards a site of high coral cover and diversity (Coral
      Gardens). Analyses of a multi-site and multi-year data set revealed no
      differences in mean temperature or turbidity values on either side of the
      causeway and provided no evidence of significantly warmer or more turbid water at
      Coral Gardens. We conclude that the putative decline in live coral cover cannot
      be attributed to the presence of the causeway and that proposed management
      actions involving modification to the causeway cannot achieve the conservation
      outcomes suggested of them. 

PMID- 24889317
TI  - Fishing down the largest coral reef fish species.
AB  - Studies on remote, uninhabited, near-pristine reefs have revealed surprisingly
      large populations of large reef fish. Locations such as the northwestern Hawaiian
      Islands, northern Marianas Islands, Line Islands, U.S. remote Pacific Islands,
      Cocos-Keeling Atoll and Chagos archipelago have much higher reef fish biomass
      than islands and reefs near people. Much of the high biomass of most remote reef
      fish communities lies in the largest species, such as sharks, bumphead parrots,
      giant trevally, and humphead wrasse. Some, such as sharks and giant trevally, are
      apex predators, but others such as bumphead parrots and humphead wrasse, are not.
      At many locations, decreases in large reef fish species have been attributed to
      fishing. Fishing is well known to remove the largest fish first, and a
      quantitative measure of vulnerability to fishing indicates that large reef fish
      species are much more vulnerable to fishing than small fish. The removal of large
      reef fish by fishing parallels the extinction of terrestrial megafauna by early
      humans. However large reef fish have great value for various ecological roles and
      for reef tourism. 

PMID- 24889318
TI  - The role of dispersants' dynamic interfacial tension in effective crude oil spill
      dispersion.
AB  - The dispersion effectiveness of dispersants containing Tween 80, Span 80, and
      dioctyl sodium sulfosuccinate (DOSS) was characterized using a modified Swirling
      Flask test, and was correlated with both initial and dynamic interfacial tension
      produced by those dispersants at an oil-water interface. Compositional trends in
      effectiveness were shown to be governed by: (1) initial oil-water interfacial
      tension observed upon dispersant-oil-saltwater contact; (2) rate of increase (or
      decrease) from the initial interfacial tension as DOSS was rapidly lost to the
      aqueous phase; and (3) gradually slowing kinetics of dispersant adsorption to the
      oil-water interface as Span 80 concentration was increased, which ultimately
      diminished dispersion effectiveness considerably even as dynamic interfacial
      tension remained <10(-3) mN/m. It is proposed that this third phenomenon results
      not only from the hydrophobicity of Span 80, but also from the dependence of
      mixed Tween-Span-DOSS reverse micelles' stability in crude oil on dispersant
      composition.

PMID- 24889319
TI  - A highly modular one-pot multicomponent approach to functionalized
      benzo[b]phosphole derivatives.
AB  - Benzo[b]phosphole derivatives have attracted significant attention for their
      unique optoelectronic properties with potential for application in materials
      science. Herein we report a modular approach to a benzo[b]phosphole derivative
      based on a one-pot sequential coupling of an arylzinc reagent, an alkyne,
      dichlorophenylphosphine (or phosphorus trichloride and a Grignard reagent), and
      an oxidant (for example H2O2, S, or Se). The approach allows for the construction
      of a library of previously inaccessible, structurally diverse benzo[b]phosphole
      derivatives with unprecedented ease.

PMID- 24889320
TI  - Three-dimensional modelling and concurrent measurements of root anatomy in
      mandibular first molar mesial roots using micro-computed tomography.
AB  - AIM: To obtain concurrent radicular measurements in the mesiobuccal (MB) and
      mesiolingual (ML) canals of mandibular first molars using scanned data of micro
      computed tomography (MUCT) with novel software. METHODOLOGY: The scanned data
      from 37 mandibular first molar mesial roots were reconstructed and analysed with
      custom-developed software (Kappa2). For each canal, three-dimensional (3D)
      surface models were re-sliced at 0.1-mm intervals perpendicular to the central
      axis. Dentine thicknesses, canal widths and 3D curvatures were measured
      automatically on each slice. Measurements were analysed statistically with anova
      for differences at each direction and at different levels of both canals.
      RESULTS: Lateral dentine thicknesses were significantly higher than mesial and
      distal thicknesses, at all the levels of both canals (P < 0.001). Mesial
      thicknesses were significantly higher than distal thicknesses in the coronal
      third of both canals (P < 0.001). Thinnest dentine thicknesses were mainly
      located on the disto-inside of both canals. Narrowest canal widths were 0.24 +/-
      0.10 and 0.22 +/- 0.09 mm in MB and ML canals, respectively. Canal curvatures
      were greatest in the apical third of both canals (P < 0.001), and they were
      greater in the MB canals than in the ML canals (P < 0.05). CONCLUSIONS: Micro
      computed tomography with novel software provided valuable anatomical information
      for optimizing instrumentation and minimizing mishaps in nonsurgical root canal
      treatment.

PMID- 24889321
TI  - A biopsychosocial approach to bipolar-borderline debate: psychological effect of
      a biological temperament.

PMID- 24889323
TI  - Topographical variations in articular cartilage and subchondral bone of the
      normal rat knee are age-related.
AB  - In osteoarthritis animal models the rat knee is one of the most frequently
      investigated joint. However, it is unknown whether topographical variations in
      articular cartilage and subchondral bone of the normal rat knee exist and how
      they are linked or influenced by growth and maturation. Detailed knowledge is
      needed in order to allow interpretation and facilitate comparability of published
      osteoarthritis studies. For the first time, the present study maps topographical
      variations in cartilage thickness, cartilage compressive properties and
      subchondral bone microarchitecture between the medial and lateral tibial
      compartment of normal growing rat knees (7 vs. 13 weeks). Thickness and
      compressive properties (aggregate modulus) of cartilage were determined and the
      subchondral bone was analyzed by micro-computed tomography. We found that
      articular cartilage thickness is initially homogenous in both compartments, but
      then differentiates during growth and maturation resulting in greater cartilage
      thickness in the medial compartment in the 13-week-old animals. Cartilage
      compressive properties did not vary between the two sites independently of age.
      In both age-groups, subchondral plate thickness as well as trabecular bone volume
      ratio and trabecular thickness were greater in the medial compartment. While a
      high porosity of subchondral bone plate with a high topographical variation
      (medial/lateral) could be observed in the 7-week-old animals, the porosity was
      reduced and was accompanied by a reversion in topographical variation when
      reaching maturity. Our findings highlight that there is a considerable
      topographical variation in articular cartilage and subchondral bone within the
      normal rat knee in relation to the developmental status. 

PMID- 24889322
TI  - The Role of Metacognitions in Expressed Emotion and Distress: A Study on
      Caregivers of Persons with First-Episode Psychosis.
AB  - BACKGROUND: In first-episode psychosis, the family is considered an important
      part in the recovery process. This is often accompanied by significant distress,
      which is acknowledged in numerous studies. However, little is known about the
      psychological factors involved. METHOD: One hundred and twenty-seven caregivers
      of persons with first-episode psychosis completed a series of questionnaires
      aimed at investigating the contribution of expressed emotion and metacognitions
      to caregiver distress. RESULTS: Linear mixed model analysis found that emotional
      over-involvement and metacognitions independently predicted caregiver distress.
      Mediation analysis using bootstrapping showed that emotional over-involvement
      could be seen as mediating the effect of metacognitions on distress. CONCLUSION:
      The current study is a first step towards understanding the role of
      metacognitions in caregiver distress, thus opening up for the possibility of
      using interventions from 'contextual behaviour therapies'. Implications and
      future studies are discussed. KEY PRACTITIONER MESSAGE: This study is the first
      attempt to address caregiver concerns from the perspective of contextual
      cognitive behavioural therapy. The metacognitive framework for caregiver distress
      in first-episode psychosis may help develop new therapeutic interventions to
      better support families. The study proposes a psychological understanding of
      emotional over-involvement and caregiver distress.

PMID- 24889324
TI  - HSP90s are required for NLR immune receptor accumulation in Arabidopsis.
AB  - Heat shock proteins (HSPs) serve as molecular chaperones for diverse client
      proteins in many biological processes. In plant immunity, cytosolic HSP90s
      participate in the assembly, stability control and/or activation of immune
      receptor complexes. In this paper we report that in addition to the well
      established positive roles that HSP90 isoforms play in plant immunity, they are
      also involved in the negative regulation of immune receptor accumulation. Point
      mutations in two HSP90 genes, HSP90.2 and HSP90.3, were identified from a forward
      genetic screen designed to isolate mutants with enhanced disease resistance. We
      found that specific mutations in HSP90.2 and HSP90.3 lead to heightened
      accumulation of immune receptors, including SNC1, RPS2 and RPS4. HSP90s may
      assist SGT1 in the formation of SCF E3 ubiquitin ligase complexes that target
      immune receptors for degradation. Such regulation is critical for maintaining
      appropriate levels of immune receptor proteins to avoid autoimmunity.

PMID- 24889325
TI  - Unintentional lethal overdose with metildigoxin in a 36-week-old infant--post
      mortem tissue distribution of metildigoxin and its metabolites by liquid
      chromatography tandem mass spectrometry.
AB  - A massive lethal overdose with beta-metildigoxin in a 36-week-old infant is
      presented. Determination of beta-metildigoxin and its metabolites digoxin,
      digoxigenin and digoxigenin-monodigitoxosid is achieved by a liquid
      chromatographic mass spectrometric (LC-MS/MS) method. Measured concentrations for
      beta-metildigoxin and digoxin in peripheral blood were 40.2 ng/ml and 25.6 ng/ml,
      respectively. Tissue distribution showed highest concentrations in kidney tissue
      and gastric content. The metabolite digoxigenin-monodigitoxosid could be detected
      in heart blood, duodenal content, gastric content and fat tissue while the
      metabolite digoxigenin could only be detected in gastric content since the drug
      was given by a stomach tube.

PMID- 24889326
TI  - Acute photo-induced toxicity and toxicokinetics of single compounds and mixtures
      of polycyclic aromatic hydrocarbons in zebrafish.
AB  - The present study examined photo-induced toxicity and toxicokinetics for acute
      exposure to selected polycyclic aromatic hydrocarbons (PAHs) in zebrafish. Photo
      enhanced toxicity from co-exposure to ultraviolet (UV) radiation and PAHs
      enhanced the toxicity and exhibited toxic effects at PAH concentrations orders of
      magnitude below effects observed in the absence of UV. Because environmental
      exposure to PAHs is usually in the form of complex mixtures, the present study
      examined the photo-induced toxicity of both single compounds and mixtures of
      PAHs. In a sensitive larval life stage of zebrafish, acute photo-induced median
      lethal concentrations (LC50s) were derived for 4 PAHs (anthracene, pyrene,
      carbazole, and phenanthrene) to examine the hypothesis that phototoxic
      (anthracene and pyrene) and nonphototoxic (carbazole and phenanthrene) pathways
      of mixtures could be predicted from single exposures. Anthracene and pyrene were
      phototoxic as predicted; however, carbazole exhibited moderate photo-induced
      toxicity and phenanthrene exhibited weak photo-induced toxicity. The toxicity of
      each chemical alone was used to compare the toxicity of mixtures in binary,
      tertiary, and quaternary combinations of these PAHs, and a predictive model for
      environmental mixtures was generated. The results indicated that the acute
      toxicity of PAH mixtures was additive in phototoxic scenarios, regardless of the
      magnitude of photo-enhancement. Based on PAH concentrations found in water and
      circumstances of high UV dose to aquatic systems, there exists potential risk of
      photo-induced toxicity to aquatic organisms.

PMID- 24889327
TI  - Sequence-based acoustic noise reduction of clinical MRI scans.
AB  - PURPOSE: Clinical MRI patients typically experience elevated acoustic noise
      levels of 80-110 dB(A). In this study, standard clinical turbo spin echo (TSE)
      and gradient echo (GRE) sequences were optimized for reduced acoustic noise at
      preserved diagnostic image quality. METHODS: The physical sources of acoustic
      noise generation in an MRI gradient coil were analyzed. A sequence conversion
      algorithm was derived that optimized the gradient time scheme for an arbitrary
      MRI sequence, preserving the governing spin physics. The algorithm was applied to
      generate "quiet" versions of standard clinical TSE and GRE sequences. RESULTS:
      The first volunteer images indicated that contrast-to-noise ratio and perceived
      diagnostic image quality remained on the same level for the algorithmic
      optimization. Additional careful TSE- and GRE-specific protocol adaptions yielded
      total acoustic noise reductions of up to 14.4 dB(A) for the TSE and up to 16.8
      dB(A) for the GRE. CONCLUSION: A physical sound pressure reduction of 81% (TSE)
      and 86% (GRE) for MRI patients was achieved. The results can be used to render
      MRI scans more patient-friendly in clinical practice, particularly for patients
      who are young, scared, or elderly.

PMID- 24889328
TI  - Chinese-English bilinguals processing temporal-spatial metaphor.
AB  - The conceptual projection of time onto the domain of space constitutes one of the
      most challenging issues in the cognitive embodied theories. In Chinese, spatial
      order (e.g.,/da shu qian/, in front of a tree) shares the same terms with
      temporal sequence (", /san yue qian/, before March). In comparison, English
      natives use different sets of prepositions to describe spatial and temporal
      relationship, i.e., "before" to express temporal sequencing and "in front of" to
      express spatial order. The linguistic variations regarding the specific lexical
      encodings indicate that some flexibility might be available in how space-time
      parallelisms are formulated across different languages. In the present study, ERP
      (Event-related potentials) data were collected when Chinese-English bilinguals
      processed temporal ordering and spatial sequencing in both their first language
      (L1) Chinese (Experiment 1) and the second language (L2) English (Experiment 2).
      It was found that, despite the different lexical encodings, early sensorimotor
      simulation plays a role in temporal sequencing processing in both L1 Chinese and
      L2 English. The findings well support the embodied theory that conceptual
      knowledge is grounded in sensory-motor systems (Gallese and Lakoff, Cogn
      Neuropsychol 22:455-479, 2005). Additionally, in both languages, neural
      representations during comprehending temporal sequencing and spatial ordering are
      different. The time-spatial relationship is asymmetric, in that space schema
      could be imported into temporal sequence processing but not vice versa. These
      findings support the weak view of the Metaphoric Mapping Theory.

PMID- 24889330
TI  - In search of the definitive Brodmann's map of cortical areas in human.

PMID- 24889329
TI  - Regulatory T cells modulate inflammation and reduce infarct volume in
      experimental brain ischaemia.
AB  - Brain ischaemia (stroke) triggers an intense inflammatory response predominately
      mediated by the accumulation of inflammatory cells and mediators in the ischaemic
      brain. In this context, regulatory T (Treg) cells, a subpopulation of CD4(+) T
      cells with immunosuppressive and anti-inflammatory properties, are activated in
      the late stages of the disease. To date, the potential therapeutic usefulness of
      Treg cells has not been tested. In this study, we aimed to investigate whether
      Treg cells exert protection/repair following stroke. Both the adoptive transfer
      of Treg cells into ischaemic rats and the stimulation of endogenous T-cell
      proliferation using a CD28 superagonist reduced the infarct size at 3-28 days
      following the ischaemic insult. Moreover, T cell-treated animals had higher
      levels of FoxP3 and lower levels of IL-1beta, CD11b+ and CD68+ cells in the
      infarcted hemisphere when compared with control animals. However, T-cell
      treatment did not alter the rate of proliferation of NeuN-, NCAM- or CD31
      positive cells, thereby ruling out neurogenesis and angiogenesis in protection.
      These results suggest that adoptive transfer of T cells is a promising
      therapeutic strategy against the neurological consequences of stroke.

PMID- 24889331
TI  - Digital biology and chemistry.
AB  - This account examines developments in "digital" biology and chemistry within the
      context of microfluidics, from a personal perspective. Using microfluidics as a
      frame of reference, we identify two areas of research within digital biology and
      chemistry that are of special interest: (i) the study of systems that switch
      between discrete states in response to changes in chemical concentration of
      signals, and (ii) the study of single biological entities such as molecules or
      cells. In particular, microfluidics accelerates analysis of switching systems
      (i.e., those that exhibit a sharp change in output over a narrow range of input)
      by enabling monitoring of multiple reactions in parallel over a range of
      concentrations of signals. Conversely, such switching systems can be used to
      create new kinds of microfluidic detection systems that provide "analog-to
      digital" signal conversion and logic. Microfluidic compartmentalization
      technologies for studying and isolating single entities can be used to
      reconstruct and understand cellular processes, study interactions between single
      biological entities, and examine the intrinsic heterogeneity of populations of
      molecules, cells, or organisms. Furthermore, compartmentalization of single cells
      or molecules in "digital" microfluidic experiments can induce switching in a
      range of reaction systems to enable sensitive detection of cells or biomolecules,
      such as with digital ELISA or digital PCR. This "digitizing" offers advantages in
      terms of robustness, assay design, and simplicity because quantitative
      information can be obtained with qualitative measurements. While digital formats
      have been shown to improve the robustness of existing chemistries, we anticipate
      that in the future they will enable new chemistries to be used for quantitative
      measurements, and that digital biology and chemistry will continue to provide
      further opportunities for measuring biomolecules, understanding natural systems
      more deeply, and advancing molecular and cellular analysis. Microfluidics will
      impact digital biology and chemistry and will also benefit from them if it
      becomes massively distributed. 

PMID- 24889332
TI  - A sustainable course in research mentoring.
AB  - In this report, we describe a six-year experience (2007-2012) in a single CTSA
      awardee institution on the development, implementation and evaluation of a hybrid
      online mentoring curriculum that is applicable to CTSA trainees at various levels
      (graduate, medical students, and junior faculty) of career training. The
      curriculum offers convenience, engagement, and financial sustainability. Overall,
      we found high levels of satisfaction with the curriculum and mentoring experience
      among both proteges and mentors. Qualitative data showed remarkable consensus of
      14 of the 15 domains of mentoring that form the framework of the mentoring
      curriculum: (1) accessibility, (2) selectivity, (3) engagement/support, (4)
      teaching/training, (5) clarity of performance/expectations, (6)
      sponsorship/sharing power judiciously, (7) demystifying the system (academia),
      (8) challenging/encouraging risk taking, (9) affirming, (10) providing
      exposure/visibility, (11) being an intentional role model, (12) protecting, (13)
      providing feedback, (14) self-disclosure, and lastly (15) counseling, with the
      fifteenth domain "counseling" being the most controversial. Quantitative survey
      data of both mentors and proteges indicated a high degree of overall satisfaction
      in their mentor-protege dyad with 86% (59) of proteges and 86% (55) of mentors
      responding good or excellent to the "quality of time spent." Mentors and proteges
      were most satisfied in the area of research, with 93% (62) of proteges and 96%
      (57) of mentors finding discussions in research very to somewhat useful for their
      own career advancement. Along with wide acceptability, this format is a useful
      option for institutions where face-to-face time is limited and education budgets
      are lean. 

PMID- 24889333
TI  - CD and NMR conformational studies of a peptide encompassing the Mid Loop
      interface of Ship2-Sam.
AB  - The lipid phosphatase Ship2 is a protein that intervenes in several diseases such
      as diabetes, cancer, neurodegeneration, and atherosclerosis. It is made up of a
      catalytic domain and several protein docking modules such as a C-terminal Sam
      (Sterile alpha motif) domain. The Sam domain of Ship2 (Ship2-Sam) binds to the
      Sam domains of the EphA2 receptor (EphA2-Sam) and the PI3K effector protein Arap3
      (Arap3-Sam). These heterotypic Sam-Sam interactions occur through formation of
      dimers presenting the canonical "Mid Loop/End Helix" binding mode. The central
      region of Ship2-Sam, spanning the C-terminal end of alpha2, the alpha3 and alpha4
      helices together with the alpha2alpha3 and alpha3alpha4 interhelical loops, forms
      the Mid Loop surface that is needed to bind partners Sam domains. A peptide
      encompassing most of the Ship2-Sam Mid Loop interface (Shiptide) capable of
      binding to both EphA2-Sam and Arap3-Sam, was previously identified. Here we
      investigated the conformational features of this peptide, through solution CD and
      NMR studies in different conditions. These studies reveal that the peptide is
      highly flexible in aqueous buffer, while it adopts a helical conformation in
      presence of 2,2,2-trifluoroethanol. The discovered structural insights and in
      particular the identification of a helical motif, may lead to the design of more
      constrained and possibly cell permeable Shiptide analogs that could work as
      efficient antagonists of Ship2-Sam heterotypic interactions and embrace
      therapeutic applications.

PMID- 24889334
TI  - Support for smoke-free cars when children are present: a secondary analysis of
      164,819 U.S. adults in 2010/2011.
AB  - Comprehensive smoke-free legislations prohibiting smoking in indoor areas of
      workplaces, bars, and restaurants have been adopted in most of the USA; however,
      limited efforts have focused on regulating secondhand smoke (SHS) exposure in the
      family car. The objective of this study was to identify the determinants and
      national/state-specific population support for smoke-free cars, in the presence
      of any occupant in general, but particularly when children are present. National
      data of US adults aged >=18 years (n = 164,819) were obtained from the 2010/2011
      Tobacco Use Supplement of the Current Population Survey. Among all US adults, a
      significantly greater proportion supported smoke-free cars when it was specified
      that the occupant was a child compared to when not specified (93.4 vs. 73.7 %, p
      < 0.05). Age, race/ethnicity, gender, current tobacco use, marital status, and
      the existence of household smoke-free regulations all mediated population support
      for smoke-free cars. CONCLUSION: While differences within the US population were
      noted, this study however showed overwhelming support for smoke-free car
      policies, particularly when children are present. Policies which prohibit smoking
      in indoor or confined areas such as cars may benefit public health by protecting
      nonsmoking children and adults from involuntary SHS exposure.

PMID- 24889335
TI  - Prediction of the risk of coronary arterial lesions in Kawasaki disease by serum
      25-hydroxyvitamin D3.
AB  - Kawasaki disease (KD) is associated with the development of coronary arterial
      lesions (CALs) in children. We aimed to test the hypothesis that circulating 25
      hydroxyvitamin D3 [25-(OH)D3] could be identified as a clinical parameter for
      predicting CALs secondary to KD in children. We enrolled 35 children with KD in
      the acute phase and measured serum 25-(OH)D3 levels in all of them, then followed
      up by echocardiography for CALs. Additionally, serum 25-(OH)D3 levels were
      obtained in 23 febrile children with respiratory tract infections and 30 healthy
      children. Of the 35 KD children, nine had CALs according to echocardiography and
      26 did not (NCALs). Serum 25-(OH)D3 levels were not significantly different
      between NCALs and healthy children (49.2 +/- 23.8 versus 44.1 +/- 30.2 ng/ml; P =
      0.49). Serum 25-(OH)D3 levels were significantly higher in children with CALs
      than those without CALs (83.9 +/- 26.3 versus 49.2 +/- 23.8 ng/ml; P = 0.001).
      The cutoff value of 65 ng/ml to predict subsequent CALs had a specificity of
      0.73, sensitivity of 0.78, and diagnostic accuracy of 0.74. CONCLUSION: Serum 25
      (OH)D3 levels were elevated dur-ing the acute phase in KD children who had
      subsequent CALs. Serum 25-(OH)D3 levels in the acute phase of KD may be used to
      predict subsequent CALs.

PMID- 24889336
TI  - Neonatal Kawasaki disease: case report and data from nationwide survey in Japan.
AB  - Kawasaki disease (KD) is a systemic vasculitis that develops during childhood,
      with a peak incidence from 6 to 23 months of age. KD also affects younger
      children, including neonates. We herein describe the case of a 22-day-old patient
      with incomplete KD. Some characteristics of neonatal KD are also presented with a
      review of nationwide surveys of KD in Japan involving approximately 130,000
      patients during a 12-year period. The surveys identified 23 neonatal cases,
      accounting for 1/5,500 of patients of all ages with KD. We found that the
      characteristics of neonatal KD are likely to be incompatible with the classic
      criteria for KD and that the incidence of coronary disorders in neonatal patients
      was not statistically higher than that in older patients. These findings are very
      similar to those of previous reports of neonatal KD. CONCLUSION: Neonatal KD is
      rare and often presents with only a few features of KD. In addition, both
      neonatal and older patients with KD are at risk of coronary disorders. These
      characteristics present a challenge to pediatricians in the diagnosis and
      treatment of febrile neonates.

PMID- 24889337
TI  - Community-supported models of care for people on HIV treatment in sub-Saharan
      Africa.
AB  - OBJECTIVES: Further scale-up of antiretroviral therapy (ART) to those in need
      while supporting the growing patient cohort on ART requires continuous adaptation
      of healthcare delivery models. We describe several approaches to manage stable
      patients on ART developed by Medecins Sans Frontieres together with Ministries of
      Health in four countries in sub-Saharan Africa. METHODS: Using routine programme
      data, four approaches to simplify ART delivery for stable patients on ART were
      assessed from a patient and health system perspective: appointment spacing for
      clinical and drug refill visits in Malawi, peer educator-led ART refill groups in
      South Africa, community ART distribution points in DRC and patient-led community
      ART groups in Mozambique. RESULTS: All four approaches lightened the burden for
      both patients (reduced travel and lost income) and health system (reduced clinic
      attendance). Retention in care is high: 94% at 36 months in Malawi, 89% at 12
      months in DRC, 97% at 40 months in South Africa and 92% at 48 months in
      Mozambique. Where evaluable, service provider costs are reported to be lower.
      CONCLUSION: Separating ART delivery from clinical assessments was found to
      benefit patients and programmes in a range of settings. The success of community
      ART models depends on sufficient and reliable support and resources, including a
      flexible and reliable drug supply, access to quality clinical management, a
      reliable monitoring system and a supported lay workers cadre. Such models require
      ongoing evaluation and further adaptation to be able to reach out to more
      patients, including specific groups who may be challenged to meet the demands of
      frequent clinic visits and the integrated delivery of other essential chronic
      disease interventions.

PMID- 24889338
TI  - Suicidal tendency in a sample of adolescent outpatients with adjustment disorder:
      gender differences.
AB  - BACKGROUND: Although Adjustment Disorder (AD) is a prevalent diagnosis in
      adolescent mental health services and linked to suicidal tendency in adolescence,
      little research exists examining prevalence and gender differences of suicidal
      symptoms among AD patients using standardized instruments. AIMS: The present
      study aims to assess the presence of suicidal tendency in a clinical sample of
      Spanish adolescents with AD analyzing gender differences. METHOD: Ninety-seven
      adolescents with AD were recruited at a public mental health center and included
      in the AD sample; they were administered the Inventario de Riesgo Suicida para
      Adolescentes (Suicide Risk Inventory for Adolescents-IRIS) and the Millon
      Adolescent Clinical Inventory (MACI). Ninety-nine community adolescents were
      recruited and administered the IRIS inventory. The community sample works as a
      contrast group. RESULTS: Girls with AD show higher levels of suicidal symptoms
      than boys on both the IRIS Suicidal Ideation and Intention scale (t=8.15, p<.001)
      and the MACI Suicidal Tendency scale (t=6.6, p<.001). Girls with AD scored
      significantly higher than girls from the community contrast group sample in the
      IRIS Suicidal Ideation and Intention scale, but boys with AD presented no
      differences with regard to boys form the community contrast group sample.
      Compared with normative clinical samples of the MACI, no differences in the
      Suicidal Tendency scale scores were found between AD and normative girls, but AD
      boys showed significantly lower mean scores than normative boys. Suicidal
      symptoms were presented by 27% of girls and 18% of boys, although only 6% of the
      girls and none of the boys presented clear suicidal tendencies. CONCLUSIONS:
      Considering suicidal tendencies in adolescents with Adjustment Disorder is
      important-especially in girls, who present high suicidal tendencies in relation
      both to boys and to community peers and the normative clinical population.

PMID- 24889339
TI  - Impulsivity in children and adolescents with mood disorders and unaffected
      offspring of bipolar parents.
AB  - OBJECTIVE: Increased impulsivity seems to be present across all phases of bipolar
      disorder (BD). Impulsivity may therefore represent an endophenotype for BD, if it
      is also found among normal individuals at high genetic risk for mood disorders.
      In this study, we assessed impulsivity across four different groups of children
      and adolescents: patients with BD, major depressive disorder (MDD) patients,
      unaffected offspring of bipolar parents (UO), and healthy controls (HC). SUBJECTS
      AND METHODS: 52 patients with BD, 31 with MDD, 20 UO, and 45 HC completed the
      Barratt Impulsiveness Scale (BIS-11), an instrument designed to measure trait
      impulsivity. RESULTS: UO displayed significantly higher total BIS-11 impulsivity
      scores than HC (p=0.02) but lower scores than BD patients (F=27.12, p<0.01).
      Multiple comparison analysis revealed higher BIS-11 total scores among BD
      patients when compared to HC (p<0.01) and UO (p<0.01). MDD patients had higher
      BIS-11 scores when compared to HC (p<0.01). Differences between MDD patients and
      UO, as well as between MDD and BD patients, were not statistically significant.
      CONCLUSION: Our findings suggest that trait impulsivity is increased among
      children and adolescents with mood disorders, as well as in unaffected
      individuals at high genetic risk for BD.

PMID- 24889340
TI  - Relationship of Internet addiction with cognitive style, personality, and
      depression in university students.
AB  - BACKGROUND: The aim of the study was to investigate the relationship of
      dysfunctional attitudes, self-esteem, personality, and depression with Internet
      addiction in university students. METHODS: A total of 720 university students
      participated in the study in Bulent Ecevit University English Preparatory School
      which offers intensive English courses. Students were evaluated with a
      sociodemographic data form, Beck Depression Inventory (BDI), Dysfunctional
      Attitudes Scale form A (DAS-A), Internet Addiction Scale (IAS), Rosenberg Self
      Esteem Scale (RSES), and Eysenck Personality Questionnaire Revised/Abbreviated
      Form (EPQR-A). RESULTS: The results indicated that 52 (7.2%) of the students had
      Internet addiction. There were 37 (71.2%) men, 15 (28.8%) women in the addicted
      group. While the addicted groups' BDI, DAS-A perfectionistic attitude, need for
      approval, RSES, EPQR-A neuroticism, and psychoticism scores were significantly
      higher, EPQR-A lie scores were significantly lower than those of the non addicted
      group. According to the multiple binary logistic regression analysis, being male,
      duration of Internet usage, depression, and perfectionistic attitude have been
      found as predictors for Internet addiction. It has been found that
      perfectionistic attitude is a predictor for Internet addiction even when
      depression, sex, duration of Internet were controlled. CONCLUSIONS: To the
      knowledge of the researchers, this study is the first study to show the
      dysfunctional attitudes in Internet addiction. It can be important to evaluate
      dysfunctional attitudes, personality, self-esteem and depression in people with
      Internet addiction. These variables should be targeted for effective treatment of
      people with Internet addiction in cognitive behavioral therapy.

PMID- 24889341
TI  - Relationship of the FKBP5 C/T polymorphism with dysfunctional attitudes
      predisposing to depression.
AB  - FK506-binding protein 51 (FKBP5) is a co-chaperone of the glucocorticoid
      receptor, and plays an important role in the negative feedback regulation of the
      hypothalamic-pituitary-adrenal axis. The C/T single nucleotide polymorphism in
      the intron 2 of the FKBP5 gene affects cortisol secretion, and has been
      implicated in the pathophysiology of depression. In this study, the relationship
      of the FKBP5 C/T polymorphism with dysfunctional attitudes predisposing to
      depression was examined. The subjects were 300 healthy Japanese. The FKBP5
      genotypes were determined by a real-time PCR and cycling probe technology for SNP
      typing. Dysfunctional attitudes were assessed by the 24-item version of the
      Dysfunctional Attitude Scale (DAS-24), which has the Achievement, Self-control,
      and Dependency subscales. DAS-24 total scores were significantly higher in the
      group with the T allele than in that without this allele (p=0.001). Regarding the
      subscales, scores of the Achievement (p=0.003) and Self-control (p=0.009)
      subscales, but not those of the Dependency subscale, were significantly higher in
      the former group than in the latter group. The present study suggests that the
      FKBP5 C/T polymorphism is implicated in formation of dysfunctional attitudes,
      especially those about achievement and self-control. 

PMID- 24889342
TI  - The validity and reliability of the Turkish version of the bipolar depression
      rating scale.
AB  - INTRODUCTION: Unipolar depression and bipolar depression differ in their clinical
      presentations, and the conventional depression rating scales fail to capture
      these differences. Recently, a new scale to rate the severity of depression in
      bipolar disorder was developed, and this study aims to evaluate the validity and
      reliability of this scale in a Turkish clinical sample. METHODS: A total of 81
      patients (30 males, 51 females) diagnosed with bipolar depression according to
      the DSM-IV-TR criteria at three different sites in Turkey were interviewed with
      the Bipolar Depression Rating Scale (BDRS), the Montgomery Asberg Depression
      Rating Scale, the Young Mania Rating Scale, and the Positive and Negative
      Syndrome Scale Depression and Excitement subscales. Internal consistency,
      interrater reliability and concurrent validity of the BDRS were evaluated.
      RESULTS: The Turkish version of the BDRS had an acceptable internal consistency
      (Cronbach's alpha=0.786). Moderate to strong correlations between the BDRS, and
      the MADRS (r=0.808), and the PANSS-D (r=0.426) were observed, and the BDRS
      correlated weakly to moderately with the PANSS-E (r=0.297), and the YMRS
      (r=0.368). The mixed symptom cluster score of the BDRS significantly correlated
      with the YMRS (r=0.755), and the PANSS-E (r=0.712). Exploratory factor analysis
      showed a three-factor solution. These factors corresponded to somatic depression,
      psychological depression, and mixed symptoms. CONCLUSIONS: This study shows that
      the Turkish version of the BDRS is a valid and reliable instrument to measure
      depressive symptomatology in bipolar disorder. The scale has good internal
      validity, strong interrater reliability, and moderate to strong correlations with
      other depression rating scales.

PMID- 24889349
TI  - The scientific basis for the use of biomaterials in stress urinary incontinence
      (SUI) and pelvic organ prolapse (POP).
AB  - OBJECTIVES: To review the scientific and clinical literature to assess the basis
      for the use of biomaterials in stress urinary incontinence (SUI) and pelvic organ
      prolapse (POP). Pelvic floor diseases (PFDS), such as SUI and POP, are common and
      vexing disorders. While synthetic mesh-based repairs have long been considered an
      option for PFD treatment, and their efficacy established in randomised clinical
      trials, safety of its use has recently been called into question. MATERIALS AND
      METHODS: Using the PubMed, MEDLINE and Medical Subject Headings (MeSH) databases,
      we performed a critical review of English-language publications that contained
      the following keywords: 'pelvic organ prolapse', 'stress urinary incontinence',
      'mesh', 'biomaterial', 'collagen', 'elastin' and 'extracellular matrix'. After
      reviewing for relevance for mesh use in the pelvis by two independent reviewers
      with a third available in the case of disagreement, a total of 60 articles were
      included in the present review. RESULTS: We found that many of the potential
      causes of PFDs are due to altered metabolism of patient extracellular matrix
      (specifically collagen, elastin, and their respective enzymes) and as such,
      repairs using native tissue may suffer from the same abnormalities leading to a
      subsequent lack of repair integrity. However, mesh use is not without its unique
      risks. Several publications have suggested that biomaterials may undergo
      alteration after implantation, but these findings have not been demonstrated in
      the normal milieu. CONCLUSION: While the decision for the use of synthetic mesh
      is scientifically sound, its benefits and risks must be discussed with the
      patient in an informed decision-making process.

PMID- 24889343
TI  - The association among food addiction, binge eating severity and psychopathology
      in obese and overweight patients attending low-energy-diet therapy.
AB  - Several studies have shown that food addiction (FA) is strongly related with
      psychopathology. However, this relationship may be partly mediated by the
      presence and severity of binge eating. The aim of the current study was to assess
      the strength of the association between FA and psychopathology, and whether this
      relationship was mediated by the presence and severity of binge eating.
      Participants were 112 patients seeking weight loss interventions. All the
      participants were administered the Yale Food Addiction Scale (YFAS), The Symptom
      Check list-90-R (SCL-90), and the Binge Eating Scale (BES). Thirty-eight (33.9%)
      individuals were diagnosed as having FA. FA severity was strongly associated with
      binge eating, whereas both FA and binge eating were positively and moderately
      associated with psychopathology. A mediational model analyzing direct and
      indirect (through the mediating role of binge eating) effects of FA on
      psychopathology indicated that the relation between FA and psychopathology was
      fully mediated by the severity of binge eating. This finding suggests that FA may
      contribute to the development of psychopathology through its effect on binge
      eating. 

PMID- 24889350
TI  - Spatially mapping charge carrier density and defects in organic electronics using
      modulation-amplified reflectance spectroscopy.
AB  - Charge-modulated optical spectroscopy is used to achieve dynamic two-dimensional
      mapping of the charge-carrier distribution in poly(3-hexylthiophene) thin-film
      transistors. The resulting in-channel distributions evolve from uniformly
      symmetric to asymmetrically saturated as the devices are increasingly biased.
      Furthermore, physical, chemical, and electrical defects are spatially resolved in
      cases where their presence is not obvious from the device performance. 

PMID- 24889351
TI  - Relation between skin micro-topography, roughness, and skin age.
AB  - BACKGROUND: The topography of the skin surface consists of lines, wrinkles, and
      scales. Primary and secondary lines form a network like structure that may be
      identified as polygons. Skin surface roughness measurements are widely applied in
      dermatological research and practice but the relation between roughness
      parameters and their anatomical equivalents are unclear. This study aimed to
      investigate whether the number of closed polygons (NCP) per measurement field can
      be used as a reliable parameter to measure skin surface topography. For this
      purpose, we analysed the relation between skin surface roughness parameters and
      NCP in different age groups. METHODS: Images of the volar forearm skin of 38
      subjects (14 children, 12 younger, and 12 older adults) were obtained with the
      VisioScan VC98. The NCP was counted by three independent researchers and selected
      roughness parameters were measured. Interrater reliability of counting the number
      of closed polygons and correlations between NCP, roughness parameters, and age
      were calculated. RESULTS: The mean NCP/mm2 in children was 3.1 (SD 1.1), in
      younger adults 1.0 (SD 0.7), and in older adults 1.0 (SD 0.9). The interrater
      reliability was 0.9. A negative correlation of NCP/mm2 with age was observed,
      whereas measured roughness parameters were positively associated with age.
      NCP/mm2 was weakly related to skin roughness. CONCLUSION: The NCP/mm2 is a
      reproducible parameter for characterizing the skin surface topography. It is
      proposed as an additional parameter in dermatological research and practice
      because it represents distinct aspects of the cutaneous profile not covered by
      established roughness parameters.

PMID- 24889352
TI  - Adhesion force measurements on the two wax layers of the waxy zone in Nepenthes
      alata pitchers.
AB  - The wax coverage of the waxy zone in Nepenthes alata pitchers consists of two
      clearly distinguishable layers, designated the upper and lower wax layers. Since
      these layers were reported to reduce insect attachment, they were considered to
      have anti-adhesive properties. However, no reliable adhesion tests have been
      performed with these wax layers. In this study, pull-off force measurements were
      carried out on both wax layers of the N. alata pitcher and on two reference
      polymer surfaces using deformable polydimethylsiloxane half-spheres as probes. To
      explain the results obtained, roughness measurements were performed on test
      surfaces. Micro-morphology of both surface samples and probes tested was examined
      before and after experiments. Pull-off forces measured on the upper wax layer
      were the lowest among surfaces tested. Here, contamination of probes by wax
      crystals detached from the pitcher surface was found. This suggests that low
      insect attachment on the upper wax layer is caused primarily by the breaking off
      of wax crystals from the upper wax layer, which acts as a separation layer
      between the insect pad and the pitcher surface. High adhesion forces obtained on
      the lower wax layer are explained by the high deformability of probes and the
      particular roughness of the substrate. 

PMID- 24889353
TI  - Retroperitoneal lymphangiectasia.

PMID- 24889354
TI  - What is your diagnosis? Abnormal cells on a blood smear from a dog.

PMID- 24889356
TI  - Extension of accompanying coordinate expansion and recurrence relation method for
      general-contraction basis sets.
AB  - An algorithm of the accompanying coordinate expansion and recurrence relation
      (ACE-RR), which is used for the rapid evaluation of the electron repulsion
      integral (ERI), has been extended to the general-contraction (GC) scheme. The
      present algorithm, denoted by GC-ACE-RR, is designed for molecular calculations
      including heavy elements, whose orbitals consist of many primitive functions with
      and without higher angular momentum such as d- and f-orbitals. The performance of
      GC-ACE-RR was assessed for (ss|ss)-, (pp|pp)-, (dd|dd)-, and (ff|ff)-type ERIs in
      terms of contraction length and the number of GC orbitals. The present algorithm
      was found to reduce the central processing unit time compared with the ACE-RR
      algorithm, especially for higher angular momentum and highly contracted orbitals.
      Compared with HONDOPLUS and GAMESS program packages, GC-ACE-RR computations for
      ERIs of three-dimensional gold clusters Aun (n = 1, 2, ..., 10, 15, 20, and 25)
      are more than 10 times faster.

PMID- 24889355
TI  - Latent time-varying factors in longitudinal analysis: a linear mixed hidden
      Markov model for heart rates.
AB  - Longitudinal data are often segmented by unobserved time-varying factors, which
      introduce latent heterogeneity at the observation level, in addition to
      heterogeneity across subjects. We account for this latent structure by a linear
      mixed hidden Markov model. It integrates subject-specific random effects and
      Markovian sequences of time-varying effects in the linear predictor. We propose
      an expectationU-maximization algorithm for maximum likelihood estimation, based
      on data augmentation. It reduces to the iterative maximization of the expected
      value of a complete likelihood function, derived from an augmented dataset with
      case weights, alternated with weights updating. In a case study of the Survey on
      Stress Aging and Health in Russia, the model is exploited to estimate the
      influence of the observed covariates under unobserved time-varying factors, which
      affect the cardiovascular activity of each subject during the observation period.

PMID- 24889357
TI  - Driving h-osteoblast adhesion and proliferation on titania: peptide hydrogels
      decorated with growth factors and adhesive conjugates.
AB  - Hydrogels from self-assembling ionic complementary peptides have been receiving
      much interest from the scientific community as mimetics of the extracellular
      matrix that can offer three-dimensional support for cell growth or become
      vehicles for the delivery of stem cells or drugs. These scaffolds have also been
      proposed as bone substitutes for small defects as they promote beneficial effects
      on human osteoblasts. In order to develop a novel bioactive titanium implant, we
      propose the introduction of a layer of ionic-complementary self-assembling
      peptides (EAbuK) on Ti whose surface has been previously sandblasted and acid
      etched. The peptide layer is anchored to the metal by covalent functionalization
      of titania with self-assembling sequences. The peptide layer has also been
      enriched by the insulin-like growth factor-1 incorporated to the layer and/or a
      conjugate obtained by chemoselective ligation between EAbuK and a sequence of 25
      residues containing four GRGDSP motifs per chain. X-ray photoelectron
      spectroscopy studies confirmed a change in the surface composition in agreement
      with the proposed decorations. An evaluation of the contact angle showed a
      substantial change in wettability induced by the peptide layer. The human
      osteoblast adhesion and proliferation assays showed an increase in adhesion for
      the surfaces enriched with conjugate at a concentration of 3.8 * 10(-7)m and an
      enhanced proliferation for samples enriched with insulin-like growth factor-1 at
      the highest concentration tested (2.1 * 10(-5)m).

PMID- 24889358
TI  - A complex genomic abnormality found in a patient with antithrombin deficiency and
      autoimmune disease-like symptoms.
AB  - Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilic
      disorder caused by SERPINC1 abnormality. In the present study, we analyzed
      SERPINC1 in a Japanese patient with AT deficiency and autoimmune disease-like
      symptoms. Direct sequencing and multiplex ligation-dependent probe amplification
      revealed that the patient was hemizygous for the entire SERPINC1 deletion. Single
      nucleotide polymorphism genotyping, gene dose measurement, and long-range
      polymerase chain reaction (PCR) followed by mapping PCR and direct sequencing of
      the long-range PCR products revealed that the patient had an approximately 111-kb
      gene deletion from exon 2 of ZBTB37 to intron 5 of RC3H1, including the entire
      SERPINC1 in chromosome 1. We also found a 7-bp insertion of an unknown origin in
      the breakpoint, which may be a combination of three parts with a few base-pair
      microhomologies, resulting from a replication-based process known as 'fork
      stalling and template switching'. Because RC3H1, which encodes the protein roquin
      is involved in the repression of self-immune responses, the autoimmune disease
      like symptoms of the patient may have resulted from this gene defect. In
      conclusion, we identified an entire SERPINC1 deletion together with a large
      deletion of RC3H1 in an AT-deficient patient with autoimmune disease-like
      symptoms. 

PMID- 24889359
TI  - Smokers with gene defect have higher risk of developing lung cancer.

PMID- 24889360
TI  - Proteomic and phosphoproteomic analyses of chromatin-associated proteins from
      Arabidopsis thaliana.
AB  - The nucleus is the organelle where basically all DNA-related processes take place
      in eukaryotes, such as replication, transcription, and splicing as well as
      epigenetic regulation. The identification and description of the nuclear proteins
      is one of the requisites toward a comprehensive understanding of the biological
      functions accomplished in the nucleus. Many of the regulatory mechanisms of
      protein functions rely on their PTMs among which phosphorylation is probably one
      of the most important properties affecting enzymatic activity, interaction with
      other molecules, localization, or stability. So far, the nuclear and subnuclear
      proteome and phosphoproteome of the model plant Arabidopsis thaliana have been
      the subject of very few studies. In this work, we developed a purification
      protocol of Arabidopsis chromatin-associated proteins and performed proteomic and
      phosphoproteomic analyses identifying a total of 879 proteins of which 198 were
      phosphoproteins that were mainly involved in chromatin remodeling,
      transcriptional regulation, and RNA processing. From 230 precisely localized
      phosphorylation sites (phosphosites), 52 correspond to hitherto unidentified
      sites. This protocol and data thereby obtained should be a valuable resource for
      many domains of plant research.

PMID- 24889361
TI  - The myriad surprises of unwanted guests: invasive plants and dynamic soil carbon
      pools.

PMID- 24889362
TI  - Catching on to concatenation: evidence for pre-pollination intra-sexual selection
      in plants.

PMID- 24889363
TI  - Organic nitrogen.

PMID- 24889364
TI  - Occlusal rehabilitation of pseudo-class III patient.
AB  - To treat a patient with anterior crossbite, the clinician should first assess if
      it is a genuine class III or a pseudo-class III malocclusion. Cephalometric
      analysis is important; however, registering a patient's centric relation (CR) is
      simple, quick, and costless and can play a decisive role in a differential
      diagnosis for this type of patient profile. This clinical report depicts a
      patient clinically diagnosed as class III. After mandible manipulation in CR, it
      was noted that the patient in question was a pseudo-class III. The treatment was
      based on the pseudo-class III diagnosis. Therefore, the patient was rehabilitated
      by occlusal adjustments and conventional and implant-supported prostheses and
      without the need for invasive orthognathic surgery. 

PMID- 24889366
TI  - ALK inhibitors and advanced non-small cell lung cancer (review).
AB  - Treatment of unselected patients with advanced non-small cell lung cancer (NSCLC)
      receiving third-generation platinum-based chemotherapy has reached a plateau of
      effectiveness. Histology and molecular analyses are the cornerstone in the
      initial diagnosis of NSCLC and are key determinants to address the appropriate
      strategy of treatment. In non-squamous histology the combination of cisplatin
      plus pemetrexed or carboplatin plus paclitaxel plus bevacizumab are considered
      today the best regimens yielding better activity and efficacy. Epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib,
      erlotinib or afatinib are the standard-of-care for patients with advanced NSCLC
      harbouring activating EGFR mutations. The identification of anaplastic lymphoma
      kinase (ALK) rearrangements in 2-5% of NSCLC patients led to the rapid clinical
      development of its oral TKI, crizotinib, also targeting the proto-oncogene MET
      and ROS1. The results reported from the first phase III trial showed superiority
      of crizotinib compared with standard chemotherapy in second-line treatment of ALK
      positive NSCLC, which was recently approved in several countries in this setting.
      Unfortunately, after initial activity of crizotinib, patients will ultimately
      develop acquired resistances within 1 or 2 years of therapy. A second generation
      of ALK inhibitors, such as LDK378, alectinib and AP26113 may represent a
      promising treatment approach: they are under investigation with very promising
      early results. This review discusses ALK rearrangements, the clinical development
      and use of crizotinib, and other ALK-TKIs in advanced NSCLC. 

PMID- 24889365
TI  - A novel role for protein arginine deiminase 4 in pluripotency: the emerging role
      of citrullinated histone H1 in cellular programming.
AB  - Histone post-translational modifications (PTMs) alter the chromatin architecture,
      generating "open" and "closed" states, and these structural changes can modulate
      gene expression under specific cellular conditions. While methylation and
      acetylation are the best-characterized histone PTMs, citrullination by the
      protein arginine deiminases (PADs) represents another important player in this
      process. In addition to "fine tuning" chromatin structure at specific loci,
      histone citrullination can also promote rapid global chromatin decondensation
      during the formation of extracellular traps (ETs) in immune cells. Recent studies
      now show that PAD4-mediated citrullination of histone H1 at promoter elements can
      also promote localized chromatin decondensation in stem cells, thus regulating
      the pluripotent state. These observations suggest that PAD-mediated histone
      deimination profoundly affects chromatin structure, possibly above and beyond
      that of other PTMs. Additionally, these recent findings further enhance our
      understanding of PAD biology and the important contributions that these enzymes
      play in development, health, and disease. 

PMID- 24889367
TI  - The effect of chelator type on in vitro receptor binding and stability in 177Lu
      labeled cetuximab and panitumumab.
AB  - Monoclonal antibodies are used in the therapy of various diseases. Thanks to
      their high specific uptake in target tissues, these antibodies can be utilized in
      targeted radioimmunotherapy as carriers of radioisotopes to tumors. However,
      important characteristics of antibodies such as target binding and stability in
      the organism may be affected by various structural parameters. This study has
      focused on the potential influence of selected chelators on radiochemical quality
      and in vitro receptor binding capacity in two modified monoclonal antibodies
      cetuximab and panitumumab, both ligands of the epidermal growth factor receptor
      (EGFR). These two antibodies were each coupled with three macrocyclic chelators
      (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7
      triazacyclononane-1,4,7-triacetic acid, and 3,6,9,15-tetraazabicyclo[9.3.1]
      pentadeca-1(15),11,13-triene-4-(S)-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid)
      and labeled with lutetium-177. The stability of the preparations was checked, and
      the cell binding to EGFR-expressing cell lines was examined. The used method led
      to very stable radiolabeled preparations. The results showed that binding to the
      target cells was not affected by the type of chelator. All three chelators may be
      useful for the labeling of cetuximab and panitumumab with lutetium-177 in future
      preclinical or clinical studies. Our study revealed previously unpublished fact
      that the type of chelator selected does not affect binding of EGFR-targeted
      antibodies labeled with lutetium-177.

PMID- 24889368
TI  - Development of anxiety-like behavior via hippocampal IGF-2 signaling in the
      offspring of parental morphine exposure: effect of enriched environment.
AB  - Opioid addiction is a major social, economic, and medical problem worldwide. Long
      term adverse consequences of chronic opiate exposure not only involve the
      individuals themselves but also their offspring. Adolescent maternal morphine
      exposure results in behavior and morphologic changes in the brain of their adult
      offspring. However, few studies investigate the effect of adult opiate exposure
      on their offspring. Furthermore, the underlying molecular signals regulating the
      intergenerational effects of morphine exposure are still elusive. We report here
      that morphine exposure of adult male and female rats resulted in anxiety-like
      behavior and dendritic retraction in the dentate gyrus (DG) region of the
      hippocampus in their adult offspring. The behavior and morphologic changes were
      concomitant with the downregulation of insulin-like growth factor (IGF)-2
      signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by
      bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented
      anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched
      environment during adolescence corrected the reduction of hippocampal IGF-2
      expression, normalized anxiety-like behavior and reversed dendritic retraction in
      the adult offspring. Thus, parental morphine exposure can lead to the
      downregulation of hippocampal IGF-2, which contributed to the anxiety and
      hippocampal dendritic retraction in their offspring. An adolescent-enriched
      environment experience prevented the behavior and morphologic changes in their
      offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment
      may be a potential intervention to prevention of anxiety and brain atrophy in the
      offspring of parental opioid exposure. 

PMID- 24889370
TI  - Dative or not dative?

PMID- 24889371
TI  - Consequences of activating the calcium-permeable ion channel TRPV1 in breast
      cancer cells with regulated TRPV1 expression.
AB  - Increased expression of specific calcium channels in some cancers and the role of
      calcium signaling in proliferation and invasion have led to studies assessing
      calcium channel inhibitors as potential therapies for some cancers. The use of
      channel activators to promote death of cancer cells has been suggested, but the
      risk of activators promoting cancer cell proliferation and the importance of the
      degree of channel over-expression is unclear. We developed an MCF-7 breast cancer
      cell line with inducible TRPV1 overexpression and assessed the role of TRPV1
      levels on cell death mediated by the TRPV1 activator capsaicin and the potential
      for submaximal activation to promote proliferation. The TRPV1 level was a
      determinant of cell death induced by capsaicin. A concentration response curve
      with varying TRPV1 expression levels identified the minimum level of TRPV1
      required for capsaicin induced cell death. At no level of TRPV1 over-expression
      or capsaicin concentration did TRPV1 activation enhance proliferation. Cell death
      induced by capsaicin was necrotic and associated with up-regulation of c-Fos and
      RIP3. These studies suggest that activators of specific calcium channels may be
      an effective way to induce necrosis and that this approach may not always be
      associated with enhancement of cancer cell proliferation. 

PMID- 24889372
TI  - Theoretical assessment of the maximum obtainable power in wireless power transfer
      constrained by human body exposure limits in a typical room scenario.
AB  - In this study, the maximum received power obtainable through wireless power
      transfer (WPT) by a small receiver (Rx) coil from a relatively large transmitter
      (Tx) coil is numerically estimated in the frequency range from 100 kHz to 10 MHz
      based on human body exposure limits. Analytical calculations were first conducted
      to determine the worst-case coupling between a homogeneous cylindrical phantom
      with a radius of 0.65 m and a Tx coil positioned 0.1 m away with the radius
      ranging from 0.25 to 2.5 m. Subsequently, three high-resolution anatomical models
      were employed to compute the peak induced field intensities with respect to
      various Tx coil locations and dimensions. Based on the computational results,
      scaling factors which correlate the cylindrical phantom and anatomical model
      results were derived. Next, the optimal operating frequency, at which the highest
      transmitter source power can be utilized without exceeding the exposure limits,
      is found to be around 2 MHz. Finally, a formulation is proposed to estimate the
      maximum obtainable power of WPT in a typical room scenario while adhering to the
      human body exposure compliance mandates. 

PMID- 24889369
TI  - Mechanisms of non-genetic inheritance and psychiatric disorders.
AB  - Inheritance is typically associated with the Mendelian transmission of
      information from parents to offspring by alleles (DNA sequence). However,
      empirical data clearly suggest that traits can be acquired from ancestors by
      mechanisms that do not involve genetic alleles, referred to as non-genetic
      inheritance. Information that is non-genetically transmitted across generations
      includes parental experience and exposure to certain environments, but also
      parental mutations and polymorphisms, because they can change the parental
      'intrinsic' environment. Non-genetic inheritance is not limited to the first
      generation of the progeny, but can involve the grandchildren and even further
      generations. Non-genetic inheritance has been observed for multiple traits
      including overall development, cardiovascular risk and metabolic symptoms, but
      this review will focus on the inheritance of behavioral abnormalities pertinent
      to psychiatric disorders. Multigenerational non-genetic inheritance is often
      interpreted as the transmission of epigenetic marks, such as DNA methylation and
      chromatin modifications, via the gametes (transgenerational epigenetic
      inheritance). However, information can be carried across generations by a large
      number of bioactive substances, including hormones, cytokines, and even
      microorganisms, without the involvement of the gametes. We reason that this
      broader definition of non-genetic inheritance is more appropriate, especially in
      the context of psychiatric disorders, because of the well-recognized role of
      parental and early life environmental factors in later life psychopathology. Here
      we discuss the various forms of non-genetic inheritance in humans and animals, as
      well as rodent models of psychiatric conditions to illustrate possible
      mechanisms. 

PMID- 24889373
TI  - The Syndrome of Inappropriate Secretion of AntiDiuretic Hormone in Patients With
      Brucellosis.
AB  - OBJECTIVE: Various studies have shown that a number of infectious disease causes
      syndrome of inappropriate antidiuretic hormone (SIADH). However, the relationship
      between infectious disease and SIADH is not yet fully known. In this prospective
      study, we aimed to assess the presence of SIADH in patients with brucellosis.
      PATIENTS AND METHODS: Thirty-five patients with acute brucellosis were
      retrospectively reviewed. The diagnosis of brucellosis was performed using the
      Wright test in connection with blood culture. SIADH was defined by euvolemic
      hyponatremia (serum sodium level lower than 135 mEq/l) with increased urinary
      sodium excretion (urinary sodium higher than 40 mmol/l). RESULTS: Of the 35
      patients, 19 (54%) had SIADH; 20 (57%) also had hypouricemia (uric acid level
      lower than 4 mg/dl). Additionally, all of the studied patients had a high mean
      urinary sodium excretion rate (mean 132 mmol/l; range 40-224). Most importantly,
      the hyponatremic patients were more likely to have a lower albumin level (P <
      0.01). CONCLUSIONS: SIADH is a major complication of brucellosis. The presence of
      SIADH could be a diagnostic tool for diagnosing brucellosis. Further larger
      randomized studies may confirm these findings.

PMID- 24889374
TI  - Elevated serum C-reactive protein, carcinoembryonic antigen and N2 disease are
      poor prognostic indicators in non-small cell lung cancer.
AB  - AIM: To assess the prognostic value of mediastinal lymph node metastases (N2
      disease), carcinoembryonic antigen (CEA) levels and C-reactive protein (CRP) in
      non-small cell lung cancer (NSCLC), according to the 7th edition of the TNM
      classification. METHODS: Newly diagnosed stage III-IV NSCLC were enrolled,
      including 75 patients with malignant pleural effusion. The relationship between
      serum CRP levels and other relevant variables such as sex, Eastern Cooperative
      Oncology Group status, smoking status, initial staging, N2 disease, serum
      albumin, white blood cell count, platelet count, CEA, comorbidity and pathology
      were analyzed. Univariate and multivariate analyses were performed to find
      prognostic markers using Cox's proportional hazards model. RESULTS: Of the 127
      patients enrolled, 55 (43%) had elevated CRP levels. There was a significant
      correlation between serum CRP level and platelet count (P = 0.011). Median
      overall survival (OS) in the normal CRP group was significantly longer than in
      the high CRP group (15.7 months vs 9.1 months, P = 0.013). Hypoalbuminemia (P =
      0.047), higher CEA (P = 0.043) and N2 disease (P = 0.040) were additional
      prognostic factors on univariate analysis. On multivariate analysis an elevated
      CRP serum level (HR = 1.796; P = 0.005), higher CEA (HR = 1.563; P = 0.031) and
      N2 disease (HR = 1.723; P = 0.012) were independent prognostic factors for poor
      survival. CONCLUSION: High levels of serum CRP and CEA, and N2 disease are
      independent prognostic indicators for the survival of patients with stage III-IV
      NSCLC.

PMID- 24889375
TI  - Relationship between frontal craniofacial morphology and horizontal balance of
      lip-closing forces during lip pursing.
AB  - The objectives of this study were to quantitatively evaluate the relationship
      between frontal craniofacial morphology and the horizontal balance of the lip
      closing forces (LCF) generated during maximum voluntary pursing-like movements in
      patients with mandibular deviation. Thirty-one subjects (median age 25.4 +/- 8.9
      years) without a history of orthodontic treatment were randomly selected from
      among the orthodontic patients who visited our hospital. Lip-closing forces was
      recorded in eight directions during maximum voluntary pursing-like lip-closing
      movements. The subjects were divided into the deviation (two males and 11
      females) and non-deviation groups (four males and 14 females). There was no
      significant difference in the total LCF between the deviation and non-deviation
      groups. In the deviation group, the mean LCF value on the deviation side of the
      upper lip was significantly lower than that detected on the non-deviation side of
      the upper lip, while the mean LCF value for the deviation side of the lower lip
      was significantly higher than that for the non-deviation side of the lower lip.
      In contrast, no significant difference in upper or lower lip LCF was detected
      between the deviation and non-deviation sides in the non-deviation group. The
      difference in the LCF generated in the lower lip between the deviation and non
      deviation sides was significantly positively correlated with mandibular menton
      deviation and significantly negatively correlated with the difference in
      maxillary height between the deviation and non-deviation sides. These results
      suggest that the horizontal balance of the upper and lower lip LCF produced
      during pursing-like lip-closing movements in patients with mandibular deviation
      is related to frontal craniofacial morphology.

PMID- 24889376
TI  - Neutral null models for diversity in serial transfer evolution experiments.
AB  - Evolution experiments with microorganisms coupled with genome-wide sequencing now
      allow for the systematic study of population genetic processes under a wide range
      of conditions. In learning about these processes in natural, sexual populations,
      neutral models that describe the behavior of diversity and divergence summaries
      have played a pivotal role. It is therefore natural to ask whether neutral
      models, suitably modified, could be useful in the context of evolution
      experiments. Here, we introduce coalescent models for polymorphism and divergence
      under the most common experimental evolution assay, a serial transfer experiment.
      This relatively simple setting allows us to address several issues that could
      affect diversity patterns in evolution experiments, whether selection is
      operating or not: the transient behavior of neutral polymorphism in an experiment
      beginning from a single clone, the effects of randomness in the timing of cell
      division and noisiness in population size in the dilution stage. In our analyses
      and discussion, we emphasize the implications for experiments aimed at measuring
      diversity patterns and making inferences about population genetic processes based
      on these measurements. 

PMID- 24889377
TI  - Assessment of soybean injury from glyphosate using airborne multispectral remote
      sensing.
AB  - BACKGROUND: Glyphosate drift onto off-target sensitive crops can reduce growth
      and yield and is of great concern to growers and pesticide applicators. Detection
      of herbicide injury using biological responses is tedious, so more convenient and
      rapid detection methods are needed. The objective of this research was to
      determine the effects of glyphosate on biological responses of non-glyphosate
      resistant (non-GR) soybean and to correlate vegetation indices (VIs) derived from
      aerial multispectral imagery. RESULTS: Plant height, shoot dry weight and
      chlorophyll (CHL) content decreased gradually with increasing glyphosate rate,
      regardless of weeks after application (WAA). Accordingly, soybean yield decreased
      by 25% with increased rate from 0 to 0.866 kg AI ha(-1) . Similarly to biological
      responses, the VIs derived from aerial imagery - normalized difference vegetation
      index, soil adjusted vegetation index, ratio vegetation index and green NDVI -
      also decreased gradually with increasing glyphosate rate, regardless of WAA.
      CONCLUSION: The VIs were highly correlated with plant height and yield but poorly
      correlated with CHL, regardless of WAA. This indicated that indices could be used
      to determine soybean injury from glyphosate, as indicated by the difference in
      plant height, and to predict the yield reduction due to crop injury from
      glyphosate.

PMID- 24889378
TI  - Ab initio study on the stability of Ng(n)Be2N2, Ng(n)Be3N2 and NgBeSiN2 clusters.
AB  - The global minima of Be2N2, Be3N2 and BeSiN2 clusters are identified using a
      modified stochastic kick methodology. The structure, stability and bonding nature
      of these clusters bound to noble gas (Ng) atoms are studied at the MP2/def2
      QZVPPD level of theory. Positive Be-Ng bond dissociation energy, which gradually
      increases down Group 18 from He to Rn, indicates the bound nature of Ng atoms.
      All of the Ng-binding processes are exothermic in nature. The Xe and Rn binding
      to Be2N2 and Be3N2 clusters and Ar-Rn binding to BeSiN2 are exergonic processes
      at room temperature; however, for the lighter Ng atoms, lower temperatures are
      needed. Natural population analysis, Wiberg bond index computations, electron
      density analysis, and energy decomposition analysis are performed to better
      understand the nature of Be-Ng bonds.

PMID- 24889379
TI  - Measurement of C-reactive protein and prostaglandin F2alpha metabolite
      concentrations in differentiation of canine pyometra and cystic endometrial
      hyperplasia/mucometra.
AB  - Canine pyometra is a dioestrus period disease in which systemic inflammatory
      response syndrome (SIRS) is a common outcome due to the response of the body to
      the bacterial infection. The purpose of this study was i) to differentiate canine
      pyometra and cystic endometrial hyperplasia (CEH)/mucometra by measuring serum C
      reactive protein (CRP) and prostaglandin F2alpha metabolite (PGFM) concentrations
      in blood and ii) to compare serum concentrations of CRP and PGFM in bitches with
      a pathological uterus (pyometra or CEH/mucometra) to concentrations in bitches
      with a healthy uterus. Mean CRP concentrations were found significantly higher (p
      < 0.001) in dogs with pyometra compared to those with CEH/mucometra or healthy
      uterus. However, no statistical difference could be detected between the groups
      for mean PGFM concentrations. Mean white blood cell count (WBC), alkaline
      phosphatase (ALP) and total protein concentrations were found significantly
      higher (p < 0.001) in dogs with pyometra. Escherichia coli was the most
      frequently isolated microorganism from dogs with pyometra (64.3%). Edwardsiella
      spp. was detected in a single case of pyometra for the first time. In conclusion,
      our results demonstrate that serum CRP concentrations were increased in dogs with
      pyometra and thus we conclude that serum CRP concentration but not PGFM might be
      useful as a marker to differentiate a case of CEH/mucometra from pyometra in
      female dogs. To the authors' knowledge, this is the first report in which
      Edwardsiella spp. has been isolated in the canine uterus.

PMID- 24889380
TI  - High-performance alkaline direct methanol fuel cell using a nitrogen-postdoped
      anode.
AB  - A commercial PtRu/C catalyst postdoped with nitrogen demonstrates a significantly
      higher performance (~10-20% improvement) in the anode of an alkaline direct
      methanol fuel cell than an unmodified commercial PtRu/C catalyst control. The
      enhanced performance shown herein is attributed at least partially to the
      increased electrochemical surface area of the PtRu/C after postdoping with
      nitrogen.

PMID- 24889381
TI  - [In Process Citation].
AB  - OBJECTIVE: To test the effectiveness of a program to improve treatment adherence
      in new onset hypertensive patients. DESIGN: This is a quasi-experimental study.
      LOCATION: Four health centers in Almeria. PARTICIPANTS: A total of 120 subjects
      between 18 and 65 years, diagnosed with hypertension within the previous 12
      months. MAIN MEASUREMENTS: The participants were divided into three groups:
      intervention group A, which received educational instruction, intervention group
      B, educational instruction and feedback process, and the control group C,
      received usual care. Adherence was determined by lifestyle (diet, physical
      activity, smoking, alcohol) and drug treatment. RESULTS: As regards diet and
      physical activity, there were significant differences between performance groups
      after intervention (p<0,05), with better adherence levels being found in group B
      subjects for these variables. Better adherence to pharmacological treatment was
      also observed in these patients. No significant results were found regarding
      alcohol and smoking. CONCLUSIONS: In the study population, patients undergoing
      educational instruction and feedback had better adherence levels than those who
      received only instruction or usual treatment.

PMID- 24889382
TI  - [Can quality care of the oncology patient be improved? Results of the
      introduction of a healthcare help line in Oncological Nursing].

PMID- 24889383
TI  - Pollen competition between two sympatric Orchis species (Orchidaceae): the
      overtaking of conspecific of heterospecific pollen as a reproductive barrier.
AB  - The frequency of hybrid formation in angiosperms depends on how and when
      heterospecific pollen is transferred to the stigma, and on the success of that
      heterospecific pollen at fertilising ovules. We applied pollen mixtures to
      stigmas to determine how pollen interactions affect siring success and the
      frequency of hybrid formation between two species of Mediterranean deceptive
      orchid. Plants of Orchis italica and O. anthropophora were pollinated with
      conspecific and heterospecific pollen (first conspecific pollen then
      heterospecific pollen and vice versa) and molecular analysis was used to check
      the paternity of the seeds produced. In this pair of Mediterranean orchids,
      competition between conspecific and heterospecific pollen functions as a post
      pollination pre-zygotic barrier limiting the frequency of the formation of
      hybrids in nature. Flowers pollinated with heterospecific pollen can remain
      receptive for the arrival of conspecific pollen for a long time. There is always
      an advantage of conspecific pollen for fruit formation, whether it comes before
      or after heterospecific pollen, because it overtakes the heterospecific pollen.
      The conspecific pollen advantage exhibited in O. italica and O. anthropophora is
      likely to result from the reduced germination of heterospecific pollen or
      retarded growth of heterospecific pollen tubes in the stigma and ovary. Overall,
      the results indicate that our hybrid zone represents a phenomenon of little
      evolutionary consequence, and the conspecific pollen advantage maintains the
      genetic integrity of the parental species. 

PMID- 24889384
TI  - Freestanding aligned carbon nanotube array grown on a large-area single-layered
      graphene sheet for efficient dye-sensitized solar cell.
AB  - A novel carbon nanomaterial with aligned carbon nanotubes (CNTs) chemically
      bonded to a single-layered, large area graphene sheet is designed and fabricated,
      showing remarkable electronic and electrocatalytic properties. When the carbon
      nanomaterial is used as a counter electrode, the resulting dye-sensitized solar
      cell exhibits ~11% enhancement of energy conversion efficiency than aligned CNT
      array. 

PMID- 24889385
TI  - Infancy predictors of hyperkinetic and pervasive developmental disorders at ages
      5-7 years: results from the Copenhagen Child Cohort CCC2000.
AB  - BACKGROUND: Epidemiological studies infancy predictors of mental disorders are
      scarce. METHODS: The study is part of a longitudinal birth-cohort study, The
      Copenhagen Child Cohort CCC2000. Infant mental health and development and mother
      infant relations were assessed by community health nurses from birth to age 10
      months. Data on the perinatal period were obtained from Danish National
      Registers. Mental health outcome at age 5-7 years was investigated in 1,585
      children who were assessed by the Developmental and Well-Being Assessment (DAWBA)
      and diagnosed according to the ICD-10. RESULTS: Predictors of autism spectrum
      disorders were problems of oral-motor development OR 5.02 (95% CI: 1.63-15.42)
      and overall development OR 4.24 (95% CI: 1.35-13.33). A deviant pattern of
      activity and interests were predictive of autism spectrum disorder, OR 5.34 (95%
      CI 1.45-19.70) and hyperkinetic disorder, OR 4.71 (95% CI: 1.28-17.39).
      Hyperkinetic disorder was furthermore predicted by mother-infant relationship
      problems, OR 8.07 (95% CI: 2.90-22.47). The significant associations between
      infant developmental problems and autism spectrum disorders persisted in multiple
      logistic regression analyses controlled for maternal psychological problems and
      mother-infant relationship problems, OR 3.21 (95% CI: 1.09-9.45). Mother-infant
      relationship problems remained strongly associated to hyperkinetic disorders in
      the multivariate analyses controlled for child development problems and maternal
      psychological problems, OR 5.20 (95% CI: 1.55-17.47). No significant infancy
      predictors were found regarding emotional and behavioural disorders at age 5-7
      years. CONCLUSION: Predictors of autism spectrum/pervasive developmental
      disorders and hyperkinetic disorders at child age 5-7 years were identified
      between birth and child age 10 months in community health settings. The study
      results suggest potential areas of early preventive intervention, which have to
      be further explored regarding the psychometric qualities of the identification of
      infants at risk, and concerning methods to handle and intervene towards these
      children in the general child health surveillance.

PMID- 24889386
TI  - Imported Plasmodium vivax malaria ex Pakistan.
AB  - BACKGROUND: According to WHO, 1.5 million cases of malaria are reported annually
      in Pakistan. Malaria distribution in Pakistan is heterogeneous, and some areas,
      including Punjab, are considered at low risk for malaria. The aim of this study
      is to describe the trend of imported malaria cases from Pakistan reported to the
      international surveillance systems from 2005 to 2012. METHODS: Clinics reporting
      malaria cases acquired after a stay in Pakistan between January 1, 2005, and
      December 31, 2012, were identified from the GeoSentinel
      (http://www.geosentinel.org) and EuroTravNet (http://www.Eurotravnet.eu)
      networks. Demographic and travel-related information was retrieved from the
      database and further information such as areas of destination within Pakistan was
      obtained directly from the reporting sites. Standard linear regression models
      were used to assess the statistical significance of the time trend. RESULTS: From
      January 2005 to December 2012, a total of 63 cases of malaria acquired in
      Pakistan were retrieved in six countries over three continents. A statistically
      significant increasing trend in imported Plasmodium vivax malaria cases acquired
      in Pakistan, particularly for those exposed in Punjab, was observed over time (p
      = 0.006). CONCLUSIONS: Our observation may herald a variation in malaria
      incidence in the Punjab province of Pakistan. This is in contrast with the
      previously described decreasing incidence of malaria in travelers to the Indian
      subcontinent, and with reports that describe Punjab as a low risk area for
      malaria. Nevertheless, this event is considered plausible by international
      organizations. This has potential implications for changes in chemoprophylaxis
      options and reinforces the need for increased surveillance, also considering the
      risk of introduction of autochthonous P. vivax malaria in areas where competent
      vectors are present, such as Europe.

PMID- 24889388
TI  - Hierarchically structured ZnO nanorods as an efficient photoanode for dye
      sensitized solar cells.
AB  - Hierarchical ZnO nanorods composed of interconnected nanoparticles, which were
      synthesized by controlling precursor concentrations in a solvothermally assisted
      process, were exploited as photoanodes in dye-sensitized solar cells (DSCs). The
      as-prepared hierarchical nanorods showed greatly enhanced light scattering
      compared to ZnO nanoparticles for boosting light harvesting while maintaining
      sufficient dye-adsorption capability. The charge-transfer characteristics were
      studied by electrochemical impedance measurements, and reduced electron
      recombination and longer electron lifetime were observed for the ZnO nanorods.
      Photovoltaic characterization demonstrated that DSCs utilizing the hierarchical
      nanorods significantly improved the overall conversion efficiency by 34 %
      compared to nanoparticle-based DSCs. 

PMID- 24889387
TI  - Accuracy of visual inspection with acetic acid to detect cervical cancer
      precursors among HIV-infected women in Kenya.
AB  - Visual inspection with acetic acid (VIA) is becoming a more widely recommended
      and implemented screening tool for cervical cancer prevention programs in low
      resource settings. Many of these settings have a high prevalence of HIV-infected
      women. We carried out a cross-sectional validation study to define the
      sensitivity, specificity and predictive values of VIA among HIV-infected women.
      Women enrolled in HIV care at the Family AIDS Care and Education Services clinic
      in Kisumu, Kenya, were recruited for participation. All participants underwent
      VIA followed by colposcopy performed by a second blinded clinician. At
      colposcopy, lesions suspicious for cervical intraepithelial neoplasia 2 or
      greater (CIN2+) were biopsied. Disease status was determined by final
      histopathologic diagnosis in women who underwent biopsies. A satisfactory
      colposcopy with no lesions was considered a negative result. From October 2010 to
      June 2012, 1,432 women underwent VIA and colposcopy. A total of 514 (35.7%) women
      had a positive VIA, and 179 (12.2%) had CIN2+ confirmed by colposcopically
      directed biopsy. Sensitivity, specificity, positive and negative predictive
      values of VIA for CIN2+ were 86.6, 71.6, 30.3 and 97.4%, respectively.
      Specificity, but not sensitivity, increased with older age. Among older women,
      sensitivity was affected by CD4+ count and use of antiretroviral therapy.
      Although they are impacted by age and immune status, test characteristics for VIA
      among HIV-infected women are similar to what has been reported for general
      populations. Recommendations to use VIA as a screening tool should not vary by
      HIV status. 

PMID- 24889389
TI  - Prognostic role of en-bloc resection and late onset of bone metastasis in
      patients with bone-seeking carcinomas of the kidney, breast, lung, and prostate:
      SSG study on 672 operated skeletal metastases.
AB  - BACKGROUND AND OBJECTIVES: In metastatic disease, decisions regarding potential
      surgery require reliable data about the patient's survival. In this study, we
      evaluated different prognostic factors and their impact in four common primary
      tumors causing bone metastases. METHODS: Data were acquired from the Scandinavian
      Sarcoma Group (SSG) metastasis registry. The patients underwent surgery between
      July 1999 and July 2009. This study included breast, prostate, lung, and kidney
      cancer cases, with a total of 672 operated non-spinal metastases. Differences in
      prognostic factors were evaluated using the Kaplan-Meier method with long-rank
      test. Cox regression multivariate analysis was performed to identify
      statistically independent prognostic factors. RESULTS: Significant factors
      affecting survival were the presence of organ metastases, overall heath status,
      and disease load. In kidney cancer, en bloc resection of solitary metastases was
      associated with a significant fourfold longer survival compared to intralesional
      surgery. Preoperative radiotherapy was associated with higher complication and
      reoperation rates. CONCLUSIONS: This data summary is important tool for
      clinicians to evaluate survival and choose treatment options for patients
      suffering from metastatic bone disease.

PMID- 24889390
TI  - Cognitive impairment in coeliac disease improves on a gluten-free diet and
      correlates with histological and serological indices of disease severity.
AB  - BACKGROUND: Mild impairments of cognition or 'Brain fog' are often reported by
      patients with coeliac disease but the nature of these impairments has not been
      systematically investigated. AIM: This longitudinal pilot study investigated
      relationships between cognitive function and mucosal healing in people with newly
      diagnosed coeliac disease commencing a gluten-free diet. METHODS: Eleven patients
      (8 females, 3 males), mean age 30 (range 22-39) years, were tested with a battery
      of cognitive tests at weeks 0, 12 and 52. Information processing efficacy,
      memory, visuospatial ability, motoric function and attention were tested. Small
      bowel biopsies were collected via routine gastroscopy at weeks 12 and 52 and were
      compared to baseline Marsh scores. Cognitive performance was compared to serum
      concentrations of tissue transglutaminase antibodies, biopsy outcomes and other
      biological markers. RESULTS: All patients had excellent adherence to the diet.
      Marsh scores improved significantly (P = 0.001, Friedman's test) and tissue
      transglutaminase antibody concentrations decreased from a mean of 58.4 at
      baseline to 16.8 U/mL at week 52 (P = 0.025). Four of the cognitive tests
      assessing verbal fluency, attention and motoric function showed significant
      improvement over the 12 months and strongly correlated with the Marsh scores and
      tissue transglutaminase antibody levels (r = 0.377-0.735; all P < 0.05). However,
      no meaningful patterns of correlations were found for nutritional or biochemical
      markers, or markers of intestinal permeability. CONCLUSIONS: In newly diagnosed
      coeliac disease, cognitive performance improves with adherence to the gluten-free
      diet in parallel to mucosal healing. Suboptimal levels of cognition in untreated
      coeliac disease may affect the performance of everyday tasks.

PMID- 24889391
TI  - Molecular epidemiology of a post-influenza pandemic outbreak of acute respiratory
      infections in Korea caused by human adenovirus type 3.
AB  - An outbreak of upper respiratory tract infections associated with human
      adenovirus (HAdV) occurred on a national scale in Korea from September to
      December 2010, following a major H1N1 influenza pandemic. Data from the Korea
      Influenza and Respiratory Surveillance System (KINRESS) showed an unusually high
      positive rate accounting for up to 20% of all diagnosed cases. To determine the
      principal cause of the outbreak, direct polymerase chain reaction (PCR)
      amplification followed by sequence analysis targeting parts of the hexon gene of
      HAdV was performed. Serotypes of 1,007 PCR-diagnosed HAdV-positive samples from
      patients with an acute upper respiratory tract illness were determined and
      epidemiological characteristics including major aged group and clinical symptoms
      were analyzed. The principal symptom of HAdV infections was fever and the
      vulnerable aged group was 1-5 years old. Based on sequence analysis, HAdV-3 was
      the predominant serotype in the outbreak, with an incidence of 74.3%. From the
      beginning of 2010 until May, the major serotypes were HAdV-1, 2, and 5 (70-100%)
      in any given period. However, an outbreak dominated by HAdV-3 started between
      July and August and peaked in September. Phylogenetic analysis revealed that
      there was no genetic variation in HAdV-3. The results demonstrated that an
      outbreak of upper respiratory illness followed by H1N1 influenza pandemic in
      Korea was caused mainly by emerged HAdV-3. J.

PMID- 24889393
TI  - The relationships between migraine, depression, anxiety, stress, and sleep
      disturbances.
AB  - To assess the relationships between migraine, depression, anxiety, stress, and
      sleep problems. Psychiatric conditions and sleep disturbances are common in
      migraineurs. Depression, anxiety, stress, migraine, and sleep problems frequently
      coexist as comorbidities. Eighty-seven episodic migraineurs (62 females, 25
      males; 32.8 +/- 6.9) and 41 control subjects (25 females, 16 males; 31.5 +/- 5.6)
      were prospectively enrolled for the study. The participants completed a
      sociodemographic data form and a migraine disability assessment scale (MIDAS),
      depression, anxiety, stress scale (DASS), and Pittsburg Sleep Quality Index
      (PSQI). In migraineurs, a significant positive correlation was found between PSQI
      total scores and MIDAS scores (migraine related disability for at least three
      consecutive months) (r = 0. 234, p = 0.04). Only 24.1 % of migraineus (n = 21)
      had minimal or no disability, 75.9 % of the patients (n = 66) had more than a
      little disability according to MIDAS scores. PSQI total scores were also
      correlated with pain intensity over a three month period (MIDAS B) (r = 0.221, p
      = 0.04). While PSQI scores were found significantly different between migraineurs
      and control subjects (5.5 +/- 2.9 vs 4.5 +/- 2.5; p = 0.04), the correlation of
      all the DASS subscale scores between the groups was not statistically
      significant. Our findings showed that episodic migraine was a risk factor on its
      own for sleep disturbances without comorbid depression, anxiety, and stress.
      Moreover, migraine-related disability and pain intensity in migraine attacks were
      related to poor sleep quality.

PMID- 24889392
TI  - Randomised controlled trial of the effects of L-ornithine on stress markers and
      sleep quality in healthy workers.
AB  - BACKGROUND: L-ornithine is a non-essential, non-protein amino acid. Although L
      ornithine is contained in various foods, the amount is usually small.Recently,
      studies have shown that orally administered L-ornithine reduced the stress
      response in animals.From these findings, we speculated that L-ornithine may play
      a role in the relieve of stress and improve sleep and fatigue symptoms in humans.
      Through a randomised, double-blind, placebo-controlled clinical study, we asked
      if L-ornithine could be beneficial to stress and sleep in healthy workers.
      METHOD: Fifty-two apparently healthy Japanese adults who had previously felt
      slight stress as well as fatigue were recruited to be study participants and were
      randomly divided into either the L-ornithine (400 mg/day) or placebo group. They
      orally consumed the respective test substance every day for 8 weeks. Serum was
      collected for the assessment of cortisol and dehydroepiandrosterone-sulphate
      (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of
      Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep
      inventory MA version (OSA-MA). RESULTS: Serum cortisol levels and the
      cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in
      comparison with the placebo group. Also, anger was reduced and perceived sleep
      quality was improved in the L-ornithine group. CONCLUSION: L-ornithine
      supplementation has the potential to relieve stress and improve sleep quality
      related to fatigue, both objectively and subjectively.

PMID- 24889395
TI  - Reply 2.

PMID- 24889394
TI  - Strategies for neurotrophin-3 and chondroitinase ABC release from freeze-cast
      chitosan-alginate nerve-guidance scaffolds.
AB  - Freeze casting, or controlled unidirectional solidification, can be used to
      fabricate chitosan-alginate (C-A) scaffolds with highly aligned porosity that are
      suitable for use as nerve-guidance channels. To augment the guidance of growth
      across a spinal cord injury lesion, these scaffolds are now evaluated in vitro to
      assess their ability to release neurotrophin-3 (NT-3) and chondroitinase ABC
      (chABC) in a controlled manner. Protein-loaded microcapsules were incorporated
      into C-A scaffolds prior to freeze casting without affecting the original
      scaffold architecture. In vitro protein release was not significantly different
      when comparing protein loaded directly into the scaffolds with release from
      scaffolds containing incorporated microcapsules. NT-3 was released from the C-A
      scaffolds for 8 weeks in vitro, while chABC was released for up to 7 weeks. Low
      total percentages of protein released from the scaffolds over this time period
      were attributed to limitation of diffusion by the interpenetrating polymer
      network matrix of the scaffold walls. NT-3 and chABC released from the scaffolds
      retained bioactivity, as determined by a neurite outgrowth assay, and the
      promotion of neurite growth across an inhibitory barrier of chondroitin sulphate
      proteoglycans. This demonstrates the potential of these multifunctional scaffolds
      for enhancing axonal regeneration through growth-inhibiting glial scars via the
      sustained release of chABC and NT-3. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24889396
TI  - Cyclopamine did not affect mouse oocyte maturation in vitro but decreased early
      embryonic development.
AB  - Hedgehog (Hh) pathway has been studied in various animal body life procedures and
      is suggested to be important for the development of multiple organs. The genes
      involved in the Hh signaling pathway were expressed in the ovary of mice, pigs
      and cattle. However, the function of Hh signaling pathway on oocyte maturation
      and early embryonic development is still controversial. We detected the effect of
      sonic hedgehog (Shh) and cyclopamine on the in vitro maturation of mouse oocytes
      and embryo development. The results showed that the presence of Shh or
      cyclopamine resulted in similar oocyte maturation to control groups. Shh did not
      improve early embryonic development. However, the supplement of cyclopamine
      depressed early embryo development. The mRNA of shh, ptch1, smo and gli1 were
      less detected in the denuded oocytes. The expression levels of ptch1 ascended
      from the uncleaved zygote to blastocyst stage. Smo or gli1 were expressed on a
      higher level at the two-cell or four-cell stage in early embryonic development
      separately. Therefore, Shh did not affect mouse oocyte maturation and early
      embryo development, but cyclopamine led to inhibited development of mouse early
      embryo. The effects of Hh signaling on the oocyte maturation and early embryo
      development might be species-specific.

PMID- 24889397
TI  - Laterality of foetal self-touch in relation to maternal stress.
AB  - This longitudinal observational study investigated whether foetuses change their
      hand preference with gestational age, and also examined the effects of maternal
      stress on lateralized foetal self-touch. Following ethical approval, fifteen
      healthy foetuses (eight girls and seven boys) were scanned four times from 24 to
      36 weeks gestation. Self-touch behaviours which resulted in a touch of the foetal
      face/head were coded in 60 scans for 10 min and analysed in terms of frequency of
      the foetuses using left and right hands to touch their face. The joint effects of
      foetal age, stress and sex on laterality were assessed. We modelled the
      proportion of right self-touches for each foetal scan using a generalized linear
      mixed model, taking account of the repeated measures design. There was
      substantial variability in hand preference between foetuses. However, there was
      no significant increase in the proportion of right-handed touches with foetal
      age. No sex differences in handedness were identified. However, maternally
      reported stress level was significantly positively related to foetal left-handed
      self-touches (odds ratio 0.915; p < .0001). This longitudinal study provides
      important new insights into the effect of recent maternal stress on foetal
      predominant hand use during self-touch. 

PMID- 24889398
TI  - Biomarkers for the diagnosis of aortic dissection.
AB  - This review discusses the role of biomarkers for both diagnoses and disease
      monitoring before, during, and after treatment of aortic dissection.

PMID- 24889399
TI  - MALDI-TOF-MS serum protein profiling for developing diagnostic models and
      identifying serum markers for discogenic low back pain.
AB  - BACKGROUND: The identification of the cause of chronic low back pain (CLBP)
      represents a great challenge to orthopedists due to the controversy over the
      diagnosis of discogenic low back pain (DLBP) and the existence of a number of
      cases of CLBP of unknown origin. This study aimed to develop diagnostic models to
      distinguish DLBP from other forms of CLBP and to identify serum biomarkers for
      DLBP. METHODS: Serum samples were collected from patients with DLBP, chronic
      lumbar disc herniation (LDH), or CLBP of unknown origin, and healthy controls
      (N), and randomly divided into a training set (n = 30) and a blind test set (n =
      30). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      was performed for protein profiling of these samples. After the discriminative
      ability of two most significantly differential peaks from each two groups was
      assessed using scatter plots, classification models were developed using
      differential peptide peaks to evaluate their diagnostic accuracy. The identity of
      peptides corresponding to three representative differential peaks was analyzed.
      RESULTS: The fewest statistically significant differential peaks were identified
      between DLBP and CLBP (3), followed by CLBP vs. N (5), DLBP vs. N (9), LDH vs.
      CLBP (20), DLBP vs. LDH (23), and LDH vs. N (43). The discriminative ability of
      two most significantly differential peaks was poor in classifying DLBP vs. CLBP
      but good in classifying DLBP vs. LDH. The accuracy of models for classification
      of DLBP vs. CLBP was not very high in the blind test (forecasting ability,
      67.24%; sensitivity, 70%), although a higher accuracy was observed for
      classification of DLBP vs. LDH and LDH vs. N (forecasting abilities, ~90%;
      sensitivities, >90%). A further investigation of three representative
      differential peaks led to the identification of two peaks as peptides of
      complement C3, and one peak as a human fibrinogen peptide. CONCLUSIONS: Our
      findings benefit not only the diagnosis of CLBP but also the understanding of the
      differences between different forms of DLBP. The ability to distinguish between
      different causes of CLBP and the identification of serum biomarkers may be of
      great value to diagnose different causes of DLBP and predict treatment efficacy.

PMID- 24889400
TI  - Challenges to ART market: a Polish case.
AB  - In the paper we are analyzing the Polish ART market. It can be noticed that the
      lack of legal regulation has resulted in many discrepancies among the policies
      adopted by various ART agencies. The social acceptance of ART procedures
      available mostly in private clinics led to growing commercialization of the
      Polish ART market. Additionally, the language of gift and altruistic rhetoric
      that are overwhelmingly employed by ART agencies reveals hypocrisy of the Polish
      ART market.

PMID- 24889401
TI  - Effect of Platform Shift/Switch on Crestal Bone Levels and Mucosal Profile
      Following Flapless Surgery and Crestal/Subcrestal Implant Placement.
AB  - BACKGROUND: Crestal remodeling/bone loss appears a common sequel to dental
      implant placement. Several hypotheses and clinical strategies have been advanced
      to explain and avert crestal remodeling; however, causative mechanisms remain
      unclear and the efficacy of clinical protocol uncertain. OBJECTIVE: The objective
      of the present study was to provide a histologic record of crestal versus
      subcrestal implant placement on crestal remodeling and mucosal profile comparing
      platform shift/switch and standard abutments following flapless implant surgery
      using a dog model. METHODS: Four dental implants each were placed into the left
      and right edentulated posterior mandibles in five adult male hound-Labrador
      mongrel dogs using a flapless approach including crestal versus subcrestal
      placement and using platform shift versus standard abutments. Block biopsies were
      collected for histological/histometric analysis following an 8-week healing
      interval. RESULTS: Both crestal and subcrestal implant installation resulted in
      significant crestal remodeling and bone loss, in particular at buccal sites,
      without significant differences between platform shift/switch and standard
      abutments. Implants installed subcrestally exhibited a significantly taller
      mucosal profile over crestal-level implants without significant differences
      between platform shift/switch and standard abutments; the epithelial attachment
      at all times arrested on the abutment surface. CONCLUSIONS: Comparing platform
      shift/switch versus standard abutments using a minimally invasive flapless
      approach including crestal or subcrestal implant placement, the platform
      shift/switch abutments offer no selective advantage over standard abutments.

PMID- 24889402
TI  - Discussion of "Combining biomarkers to optimize patient treatment
      recommendations" by Chaeryon Kang, Holly Janes, and Ying Huang.

PMID- 24889404
TI  - A prospective study of perceived injustice in whiplash victims and its
      relationship to recovery.
AB  - The objectives of this paper are to to measure levels of perceived injustice in
      whiplash victims and determine the relationship to recovery at 6-month post
      injury. Consecutive acute whiplash patients completed the Injustice Experience
      Questionnaire, at presentation, and also 3- and 6-month post-injury. At each of
      these two follow-up points, participants were examined for recovery. Of an
      initial 134 participants, 130 participants were followed up at 3 months and 124
      at 6 months. At the 3-month follow-up, 62 % (80/130) of participants reported
      recovery from their injuries. At 6 months, 80 % (99/124) reported recovery. The
      initial Injustice Experience Questionnaire score was low, with a mean score of
      6.0 +/- 1.0 (range 5-10) out of a maximum of 48. The mean score at 3-month follow
      up had increased in the cohort to 7.4 +/- 1.6 (range 5-11). At 6-month post
      injury, the mean of the Injustice Experience Questionnaire score for the cohort
      who still reported lack of recovery (25/124 participants) was 15.0 +/- 6.0 (range
      5-31), while that for the recovered group remained low at 8.2 +/- 3.9 (range 5
      11). In the primary care setting, a significant proportion of whiplash patients
      who have not recovered by 3-month post-injury subsequently develop higher levels
      of perceived injustice by 6-month post-injury. The development of high levels of
      perceived injustice at 6-month post-injury appears to follow the development of
      chronic pain and a lack of recovery at 3 months and, at that point, becomes a
      risk factor for lack of recovery thereafter.

PMID- 24889403
TI  - Impact and therapy of osteoarthritis: the Arthritis Care OA Nation 2012 survey.
AB  - Osteoarthritis (OA) is the fastest growing cause of disability worldwide. The aim
      of this study was to understand the impact of OA on individuals and to explore
      current treatment strategies. An online UK-wide survey of people with self
      reported OA was conducted, composed of 52 questions exploring the impact of OA,
      diagnosis and treatment, the role of health professionals and self-management.
      Four thousand forty-three people were invited with 2,001 respondents (49 %
      response, 56 % women; mean age 65 years). Fifty-two percent reported that OA had
      a large impact on their lives. Fifteen percent of respondents had taken early
      retirement on average 7.8 years earlier than planned. In consultations with
      general practitioners, only half reported a discussion on pain; fewer reported
      discussing their fears (21 %) or management goals (15 %). Nearly half (48 %)
      reported not seeking medical help until pain was frequently unbearable. Oral
      analgesics (62 %), topical therapies (47 %), physiotherapy (38 %) and steroid
      injections (28 %) were commonly used. The majority (71 %) reported varying
      degrees of persistent pain despite taking all prescribed medication. Although 64
      % knew that increasing exercise was important, only 36 % acted on this knowledge;
      87 % who increased exercise found it beneficial. Over half had future concerns
      related to mobility (60 %), maintaining independence (52 %) and coping with
      everyday activities (51 %). OA had significant individual economic impact
      especially on employment. Current treatment strategies still leave most people in
      pain with significant fears for the future. There is considerable opportunity to
      improve the holistic nature of OA consultations especially in provision of
      information and promotion of self-management strategies.

PMID- 24889405
TI  - T cell ALL presenting as seropositive rheumatoid arthritis: case report and
      review of the literature on seropositive paraneoplastic arthritis.
AB  - We present the case of a 61-year-old female with an acute onset of polyarthritis
      involving the wrists, hands, knees, and ankles. Associated systemic symptoms
      included fever, weight loss, and lymphadenopathy. Serologic workup revealed
      positive rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP)
      antibodies. Radiograph imaging of her bilateral hands and wrists showed erosive
      joint disease and lymph node, and bone marrow biopsy confirmed a diagnosis of T
      cell lymphoblastic leukemia. Our case demonstrates a unique clinical phenotype of
      paraneoplastic arthritis and is only the second reported case of RF, anti-CCP
      positive arthritis related to a hematological malignancy. We review the only
      three published cases of seropositive paraneoplastic arthritis. In each case,
      systemic symptoms or a poor response to steroid treatment triggered additional
      workup. These cases highlight the importance of careful clinical assessment and
      vigilance to rule out secondary causes of inflammatory arthritis, even in
      patients with seropositive erosive arthritis.

PMID- 24889406
TI  - Incidence and cost of hospitalizations associated with Staphylococcus aureus skin
      and soft tissue infections in the United States from 2001 through 2009.
AB  - BACKGROUND: The emergence of community-associated methicillin-resistant
      Staphylococcus aureus (SA) and its role in skin and soft tissue infections
      (SSTIs) accentuated the role of SA-SSTIs in hospitalizations. METHODS: We used
      the Nationwide Inpatient Sample and Census Bureau data to quantify population
      based incidence and associated cost for SA-SSTI hospitalizations. RESULTS: SA
      SSTI associated hospitalizations increased 123% from 160,811 to 358,212 between
      2001 and 2009, and they represented an increasing share of SA- hospitalizations
      (39% to 51%). SA-SSTI incidence (per 100,000 people) doubled from 57 in 2001 to
      117 in 2009 (p<0.01). A significant increase was observed in all age groups.
      Adults aged 75+ years and children 0-17 years experienced the lowest (27%) and
      highest (305%) incidence increase, respectively. However, the oldest age group
      still had the highest SA-SSTI hospitalization incidence across all study years.
      Total annual cost of SA-SSTI hospitalizations also increased and peaked in 2008
      at $4.84 billion, a 44% increase from 2001. In 2009, the average associated cost
      of a SA-SSTI hospitalization was $11,622 (SE=$200). CONCLUSION: There has been an
      increase in the incidence and associated cost of SA-SSTI hospitalizations in
      U.S.A. between 2001 and 2009, with the highest incidence increase seen in
      children 0-17 years. However, the greatest burden was still seen in the
      population over 75 years. By 2009, SSTI diagnoses were present in about half of
      all SA-hospitalizations.

PMID- 24889407
TI  - Reduced tumour necrosis factor receptor superfamily 13C inversely correlated with
      tumour necrosis factor superfamily 13B in patients with immune thrombocytopenia.
AB  - To investigate the expression of tumour necrosis factor superfamily 13B
      (TNFSF13B) receptors in immune thrombocytopenia (ITP) and their correlation with
      disease activity, we investigated the protein and mRNA levels of TNFSF13B, tumour
      necrosis factor receptor superfamily 13C (TNFRSF13C), TNFRSF13B and TNFRSF17 by
      flow cytometry, enzyme-linked immunosorbent assay and real time quantitative
      polymerase chain reaction. All CD19(+) B lymphocytes expressed TNFRSF13C by flow
      cytometry, but the mean fluorescence intensity (MFI) was decreased in patients
      with active disease compared to patients in remission and healthy controls, while
      no significant difference of TNFRSF13C mRNA was found between ITP patients and
      controls. The mRNA and plasma TNFSF13B were elevated in active ITP patients, and
      TNFRSF13C MFI level was inversely correlated with plasma TNFSF13B in active
      patients. In vitro assays showed that TNFRSF13C MFI was decreased after long
      exposure to TNFSF13B. No significant difference for TNFRSF13B or TNFRSF17 was
      found between ITP patients and controls. In conclusion, TNFRSF13C expression is
      reduced on CD19(+) cells in active ITP patients. This down-regulation occurs
      through a post-transcriptional mechanism and could be a consequence of chronic
      increase of TNFSF13B. 

PMID- 24889408
TI  - An autopsy case of a ruptured pseudoaneurysm of the ascending aorta complicated
      by previous cardiac surgery for ventricular septal defect.
AB  - A man in his thirties was found dead in bed. He had undergone repair of a
      ventricular septal defect in his infancy and had a 2-month history of antemortem
      chest pain. On autopsy, a ruptured saccular aneurysm of the ascending aorta was
      identified, and the right thoracic cavity was found to contain coagulated blood.
      The oval ostium of the aneurysm was smoothly endothelialized and a black suture
      was found near its edge. Histological analysis revealed a defect of the intimal
      and medial layers in the wall of the aneurysm and hypertensive changes in several
      organs. The cause of death was presumed to be the rupture of a pseudoaneurysm at
      the aortic cannulation site after a long postoperative period. In the present
      case, preexisting hypertension was suspected as the cause of the formation and
      rupture of the pseudoaneurysm. In case of unexpected death, it is important to
      examine the past medical history even after a long postoperative period. 

PMID- 24889410
TI  - A layered erbium phosphonate in pseudo-D(5h) symmetry exhibiting field-tunable
      magnetic relaxation and optical correlation.
AB  - A layered erbium(III) phosphonate compound, [Er(notpH4)(H2O)]ClO4.3H2O (1), in
      which the Er(III) ion has a pseudo-D5h symmetry exhibits field tunable multiple
      magnetic relaxation. The near-IR emission spectrum of 1, excited at 1064 nm
      (Nd:YAG laser), provides a direct probe of the crystal field splitting correlated
      to the magnetic data.

PMID- 24889409
TI  - Postmortem distribution of alpha-pyrrolidinobutiophenone in body fluids and solid
      tissues of a human cadaver.
AB  - We experienced an autopsy case of a 21-year-old male Caucasian, in which the
      direct cause of his death was judged as subarachnoid hemorrhage. There was
      cerebral arteriovenous malformation, which seemed related to the subarachnoid
      hemorrhage. The postmortem interval was estimated to be about 2days. By our drug
      screening test using gas chromatography-mass spectrometry, we could identify
      alpha-pyrrolidinobutiophenone (alpha-PBP) in his urine specimen, which led us to
      investigate the postmortem distribution of alpha-PBP in this deceased. The
      specimens dealt with were right heart blood, left heart blood, femoral vein
      blood, cerebrospinal fluid, urine, stomach contents and five solid tissues. The
      extraction of alpha-PBP and alpha-pyrrolidinovalerophenone (alpha-PVP, internal
      standard) was performed by a modified QuEChERS (quick, easy, cheap, effective,
      rugged and safe) method, followed by the analysis by liquid chromatography-tandem
      mass spectrometry. Because this study included various kinds of human matrices,
      we used the standard addition method to overcome the matrix effects. The highest
      concentration was found in urine, followed by stomach contents, the kidney, lung,
      spleen, pancreas and liver. The blood concentrations were about halves of those
      of the solid tissues. The high concentrations of alpha-PBP in urine and the
      kidney suggest that the drug tends to be rapidly excreted into urine via the
      kidney after its absorption into the blood stream. The urine specimen is of the
      best choice for analysis. This is the first report describing the postmortem
      distribution of alpha-PBP in a human to our knowledge. 

PMID- 24889411
TI  - Australian and New Zealand evidence-based recommendations for pain management by
      pharmacotherapy in adult patients with inflammatory arthritis.
AB  - AIM: To develop Australian and New Zealand evidence-based recommendations for
      pain management by pharmacotherapy in adult patients with optimally treated
      inflammatory arthritis (IA). METHODS: Four hundred and fifty-three
      rheumatologists from 17 countries including 46 rheumatologists from Australia and
      New Zealand participated in the 2010 3e (Evidence, Expertise, Exchange)
      Initiative. Using a formal voting process, rheumatologists from 15 national
      scientific committees selected 10 clinical questions regarding the use of pain
      medications in IA. Bibliographic fellows undertook a systematic literature review
      for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008-09 EULAR/ACR
      abstracts. Relevant studies were retrieved for data extraction and risk of bias
      assessment. Rheumatologists from Australia and New Zealand used the evidence to
      develop a set of national recommendations. These recommendations were then
      formulated and assessed for agreement and the potential impact on clinical
      practice. The Oxford Levels of Evidence and Grade of Recommendation were applied
      to each recommendation. RESULTS: The systematic reviews identified 49 242
      references, from which 167 studies which met the pre-specified inclusion
      criteria. Combining this evidence with expert opinion led to the development of
      10 final Australian and New Zealand recommendations. The recommendations relate
      to pain measurement, and the use of analgesic medications in patients with and
      without co-morbidities and during pregnancy and lactation. The recommendations
      reflect the clinical practice of the majority of the participating
      rheumatologists (mean level of agreement 7.24-9.65). CONCLUSIONS: Ten Australian
      and New Zealand evidence-based recommendations regarding the management of pain
      by pharmacotherapy in adults with optimally treated IA were developed. They are
      supported by a large panel of rheumatologists, thus enhancing their utility in
      everyday clinical practice.

PMID- 24889412
TI  - Transfusion indication predictive score: a proposed risk stratification score for
      perioperative red blood cell transfusion in cardiac surgery.
AB  - BACKGROUND AND OBJECTIVES: Red blood cell transfusion is known to be associated
      with increased morbidity and mortality in cardiac surgery. This study was
      performed to derive a score to predict that risk in our patients. MATERIALS AND
      METHODS: Clinical details of patients who underwent cardiac surgery at the Sultan
      Qaboos University Hospital over 5 years were reviewed. We used univariable and
      multivariable logistic regression to develop the score, the Hosmer-Lemeshow test
      for calibration, the receiver operator curve for discrimination and the bootstrap
      procedure for internal validation. RESULTS: The sample included 413 patients. The
      following were found to be statistically significant transfusion predictors
      (score given): cerebrovascular disease (4), use of aspirin or clopidogril within
      7 days of surgery (3), non-elective surgery (2), haematocrit <35% (2), glucose-6
      phosphate dehydrogenase (G6PD) deficiency (2), use of cardiopulmonary bypass (2),
      age > 60 years (1), diabetes mellitus (1) and male gender (-2). We classified the
      observations into three groups: group 1 with total score of <2, group 2 with
      total score of 2-5 and group 3 with total score of >5. The calculated
      probabilities of receiving transfusion were 42%, 63% and 91% for groups 1, 2 and
      3 respectively. CONCLUSION: We derived a simple score that can be utilized to
      assess the need of blood transfusion in patients undergoing cardiac surgery. We
      are the first to report G6PD deficiency and history of cerebrovascular disease as
      predictors. We recommend prospective external validation of the proposed score on
      a larger cohort of patients.

PMID- 24889413
TI  - Is radical surgery feasible in liver hydatid cysts in contact with the inferior
      vena cava?
AB  - BACKGROUND: Cysts in contact with the inferior vena cava (IVC) represent a
      challenge for hepato-pancreatico-biliary surgeons. Although the literature on the
      topic is scarce, the most widely accepted approach is conservative surgery.
      Partial cyst resection is recommended, because radical resection is considered a
      high-risk procedure. STUDY DESIGN: This was a retrospective study over the period
      January 2007-December 2012. We operated on 103 patients with liver hydatidosis. A
      total of 32 patients (31 %) had a liver cyst in contact with the IVC. We proposed
      a cyst classification based on location of the cyst and length of contact and
      degrees of involvement of the IVC. RESULTS: Median size of the contacting cyst
      measured by computed tomography (CT) was 12 cm. On CT, median length of contact
      with the IVC was 37 mm. The median degree of involvement was 90 degrees . Radical
      surgery was performed in 20 patients (62.5 %). No IVC resection was done.
      Morbidity rate was 28 %, and mortality was 3 %. In follow-up (median 27 months),
      no relapses or problems related to IVC flow were detected. Postoperative stay and
      transfusion rate were higher in the conservative surgery group, but these
      patients presented fewer complications. There was no relationship between
      circumferential grades and length of contact with the IVC and the type of surgery
      performed. CONCLUSIONS: Liver hydatid cysts in contact with the IVC are large
      cysts usually located in the right liver. They do not normally cause clinical
      symptoms related to IVC contact. Radical surgery is feasible, and was performed
      in 60 % of our series, but it is technically demanding. We propose a
      classification of cysts in contact with the IVC.

PMID- 24889414
TI  - Pregnancy in beta-thalassemia intermedia: 20-year experience of a Greek
      thalassemia center.
AB  - OBJECTIVE: Progress in the management of patients with thalassemia intermedia
      (TI) enabled increasing rates of pregnancies among TI women worldwide.
      Nevertheless, information regarding TI pregnancy management and outcome is quite
      limited in the literature. The aim of this study was to report our experience
      regarding the maternal and fetal outcome of TI patients, as well as to depict the
      complexity of the disease and the need for multidisciplinary and personalized
      management as shown by the description of two interesting pregnancy cases.
      METHODS: We analyzed our data recorded from 60 pregnancies in 34 women over a 20
      yr period. RESULTS: Forty-nine patients achieved full-term pregnancies (mean
      maternal age +/- SD: 27.4 +/- 6.5 yr) within 37 +/- 3 gestation weeks. Their mean
      hemoglobin value was 8.33 +/- 1.22 g/dL; 26.5% of patients were not transfused at
      all or they had been transfused only once during gestation. There were 11
      abortions (18.3%). The spontaneous abortions (5/11) were related to high HbF
      levels. Six patients had more than two normal deliveries. Nineteen newborns
      (38.8%), which weighed 2-3 kg, required hospitalization to an intensive neonatal
      care unit for 1-3 wk. One patient presented with life-threatening complications
      (hemolytic anemia, thrombocytopenia, and enlargement of spleen) and another with
      spastic paraparesis due to extramedullary paravertebral masses. CONCLUSIONS:
      Although several complications can occur during a pregnancy in TI women, the
      careful and frequent monitoring by both hamatologists and obstetricians can lead
      to successful deliveries.

PMID- 24889416
TI  - Efficient odd straight medium chain free fatty acid production by metabolically
      engineered Escherichia coli.
AB  - Free fatty acids (FFAs) can be used as precursors for the production of biofuels
      or chemicals. Different composition of FFAs will be useful for further
      modification of the biofuel/biochemical quality. Microbial biosynthesis of even
      chain FFAs can be achieved by introducing an acyl-acyl carrier protein
      thioesterase gene into E. coli. In this study, odd straight medium chain FFAs
      production was investigated by using metabolic engineered E. coli carrying acyl
      ACP thioesterase (TE, Ricinus communis), propionyl-CoA synthase (Salmonella
      enterica), and beta-ketoacyl-acyl carrier protein synthase III (four different
      sources) with supplement of extracellular propionate. By using these
      metabolically engineered E. coli, significant quantity of C13 and C15 odd
      straight-chain FFAs could be produced from glucose and propionate. The highest
      concentration of total odd straight chain FFAs attained was 1205 mg/L by the
      strain HWK201 (pXZ18, pBHE2), and 85% of the odd straight chain FFAs was C15.
      However, the highest percentage of odd straight chain FFAs was achieved by the
      strain HWK201 (pXZ18, pBHE3) of 83.2% at 48 h. This strategy was also applied
      successfully in strains carrying different TE, such as the medium length acyl-ACP
      thioesterase gene from Umbellularia californica. C11 and C13 became the major odd
      straight-chain FFAs.

PMID- 24889417
TI  - Discrimination by health care workers versus discrimination by others:
      countervailing forces on HCV treatment intentions.
AB  - Hepatitis C virus (HCV) infection is a major public health burden. Despite recent
      advances in HCV treatment, uptake remains low, particularly amongst people who
      inject drugs. HCV-related stigma and discrimination are common, especially within
      the health care sector. This research examines a more nuanced approach for how
      HCV-related stigma and discrimination impacts treatment access and uptake. Based
      on a social identity framework, we explore whether perceived HCV-related
      discrimination is associated with attempts to remove the stigma of being HCV
      positive via HCV treatment intentions. Based on the results of prior research it
      was also hypothesised that the source of discrimination (health care workers
      versus others), and whether the discrimination is perceived to be directed to
      oneself or to the HCV-positive group, will differentially impact treatment
      intentions. The sample consisted of 416 people living with HCV in New South
      Wales, Australia, who acquired HCV from injecting drugs. Participants were asked
      about their experiences of perceived discrimination directed towards themselves
      versus their HCV-positive group and perceived discrimination within the health
      care sector. Findings indicate that discrimination towards the self is a more
      powerful indicator of treatment intentions than discrimination aimed at the HCV
      positive group. This finding is consistent with social identity theory suggesting
      that people from low status groups are motivated to change their stigmatised
      status when it is possible to do so. The source of the perceived discrimination
      also matters, however, as participants who report experiencing discrimination
      from health workers have lowered intentions to engage with HCV treatment in the
      future. In combination, the results indicate that while perceived discrimination
      is commonly understood to act as a barrier to treatment uptake, the relationship
      is actually more complex than previously conceptualised. 

PMID- 24889415
TI  - Using frozen section to identify histological patterns in stage I lung
      adenocarcinoma of <= 3 cm: accuracy and interobserver agreement.
AB  - AIMS: The IASLC/ATS/ERS classification of lung adenocarcinoma provides a
      prognostically significant histological subclassification. The aim of this study
      was to investigate the accuracy, limitations and interobserver agreement of
      frozen sections for predicting histological subtype. METHODS AND RESULTS: Frozen
      section and permanent section slides from 361 resected stage I lung
      adenocarcinomas <= 3 cm in size were reviewed for predominant histological
      subtype and the presence or absence of lepidic, acinar, papillary, micropapillary
      and solid patterns. Fifty cases were additionally reviewed by three pathologists
      to determine interobserver agreement. To test the accuracy of frozen section in
      judging degree of invasion, five pathologists reviewed frozen section slides from
      35 cases with a predominantly lepidic pattern. There was moderate agreement on
      predominant histological subtype between frozen sections and final diagnosis
      (kappa = 0.565). Frozen sections had high specificity for micropapillary and
      solid patterns (94% and 96%, respectively), but sensitivity was low (37% and 69%,
      respectively). The interobserver agreement was satisfactory (kappa > 0.6, except
      for the acinar pattern). CONCLUSIONS: Frozen section can provide information on
      the presence of aggressive histological patterns-micropapillary and solid-with
      high specificity but low sensitivity. It was difficult to predict the predominant
      pattern on the basis of frozen sections, mostly because of sampling issues.

PMID- 24889418
TI  - Sex hormone-binding globulins characterization and gonadal gene expression during
      sex differentiation in the rainbow trout, Oncorhynchus mykiss.
AB  - Sex hormone-binding globulin (SHBG) binds androgens and estrogens in the blood of
      many vertebrates, including teleost fish. In mammals, SHBG is synthetized in the
      liver and secreted into the blood. In fish, shbga also exhibits a hepatic
      expression. In salmonids, in which the gene has been duplicated, the recently
      discovered shbgb gene exhibits a predominantly ovarian expression. The present
      work aimed at gaining new insight into shbgb gene structure and expression during
      gonadal sex differentiation, a steroid-sensitive process, and Shbgb protein
      structure and binding characteristics; specifically, rainbow trout (Oncorhynchus
      mykiss) shbgb was analyzed. shbgb structure was analyzed in silico while
      expression was characterized during gonadal sex differentiation using all-male
      and all-female populations. We observed that shbgb gene and cognate-protein
      structures are similar to homologs previously described in zebrafish and mammals.
      The shbgb gene is predominantly expressed in differentiating female gonads, with
      increased expression around the end of ovarian differentiation. In the ovary,
      shbgb mRNA was detected in a subset of somatic cells surrounding the ovarian
      lamellae. Furthermore, Shbgb binds steroids with a higher selectivity than Shbga,
      exhibiting a higher affinity for estradiol compared to Shbga. In conclusion,
      Shbgb binding characteristics are clearly different from those of Shbga. Shbgb is
      expressed in the differentiating ovary during a period when the synthesis and
      action of testosterone and estradiol must be tightly regulated. This strongly
      suggests that Shbgb participates in the regulation of steroid metabolism and/or
      mediation, that is, needed during early gonadal development in rainbow trout.

PMID- 24889419
TI  - Redox heterogeneity of subsurface waters in the Mesoproterozoic ocean.
AB  - A substantial body of evidence suggests that subsurface water masses in mid
      Proterozoic marine basins were commonly anoxic, either euxinic (sulfidic) or
      ferruginous (free ferrous iron). To further document redox variations during this
      interval, a multiproxy geochemical and paleobiological investigation was
      conducted on the approximately 1000-m-thick Mesoproterozoic (Lower Riphean) Arlan
      Member of the Kaltasy Formation, central Russia. Iron speciation geochemistry,
      supported by organic geochemistry, redox-sensitive trace element abundances, and
      pyrite sulfur isotope values, indicates that basinal calcareous shales of the
      Arlan Member were deposited beneath an oxygenated water column, and consistent
      with this interpretation, eukaryotic microfossils are abundant in basinal facies.
      The Rhenium-Osmium (Re-Os) systematics of the Arlan shales yield depositional
      ages of 1414+/-40 and 1427+/-43 Ma for two horizons near the base of the
      succession, consistent with previously proposed correlations. The presence of
      free oxygen in a basinal environment adds an important end member to Proterozoic
      redox heterogeneity, requiring an explanation in light of previous data from time
      equivalent basins. Very low total organic carbon contents in the Arlan Member are
      perhaps the key--oxic deep waters are more likely (under any level of atmospheric
      O2) in oligotrophic systems with low export production. Documentation of a full
      range of redox heterogeneity in subsurface waters and the existence of local
      redox controls indicate that no single stratigraphic section or basin can
      adequately capture both the mean redox profile of Proterozoic oceans and its
      variance at any given point in time.

PMID- 24889420
TI  - A vision-based system for fast and accurate laser scanning in robot-assisted
      phonomicrosurgery.
AB  - PURPOSE: Surgical quality in phonomicrosurgery can be improved by open-loop laser
      control (e.g., high-speed scanning capabilities) with a robust and accurate
      closed-loop visual servoing systems. A new vision-based system for laser scanning
      control during robot-assisted phonomicrosurgery was developed and tested.
      METHODS: Laser scanning was accomplished with a dual control strategy, which adds
      a vision-based trajectory correction phase to a fast open-loop laser controller.
      The system is designed to eliminate open-loop aiming errors caused by system
      calibration limitations and by the unpredictable topology of real targets.
      Evaluation of the new system was performed using CO(2) laser cutting trials on
      artificial targets and ex-vivo tissue. RESULTS: This system produced accuracy
      values corresponding to pixel resolution even when smoke created by the laser
      target interaction clutters the camera view. In realistic test scenarios,
      trajectory following RMS errors were reduced by almost 80 % with respect to open
      loop system performances, reaching mean error values around 30 MU m and maximum
      observed errors in the order of 60 MU m. CONCLUSION: A new vision-based laser
      microsurgical control system was shown to be effective and promising with
      significant positive potential impact on the safety and quality of laser
      microsurgeries.

PMID- 24889422
TI  - Investigating muscle regeneration with a dermis/small intestinal submucosa
      scaffold in a rat full-thickness abdominal wall defect model.
AB  - Repair of large complex ventral wall hernias is challenging and outcomes are
      often poor due to hernia recurrence and compromised abdominal wall function.
      Currently, biological grafts are used to assist in repairing these complex
      hernias. Dermis grafts are often chosen because of their mechanical
      characteristics; however, dermis does not have the ability to promote the muscle
      regeneration needed to regain abdominal wall function. In contrast, small
      intestinal submucosa (SIS) grafts have been shown to promote muscle generation in
      volumetric muscle loss (VML) models. Hence, the objective of this study is to
      investigate the extent to which SIS grafts can be used together with dermis
      grafts to repair and promote muscle regeneration in a full-thickness abdominal
      wall defect in a rat model. The dermis layer is intended to mechanically bridge
      the defect and support constructive tissue remodeling while the SIS is intended
      to degrade and promote neo-muscle formation. After 16 weeks of implantation, we
      found only a small amount of vascularized muscle (<10% of the defect area) in the
      repaired defects. No significant difference in defect muscle area was found
      between the groups receiving the dermis + SIS scaffolds and the control (dermis
      alone) group. Our findings indicate that the SIS constructions investigated could
      not promote appreciable muscle regeneration in this rigorous animal model of VML
      and incomplete abdominal closure. Future investigation into combination scaffold,
      cell and molecular therapies would be warranted to address the need for
      functional muscle regeneration in challenging clinical conditions such as complex
      abdominal wall repair.

PMID- 24889421
TI  - N-acetylcysteine reduces oxidative stress, nuclear factor-kappaB activity and
      cardiomyocyte apoptosis in heart failure.
AB  - The roles of oxidative stress on nuclear factor (NF)-kappaB activity and
      cardiomyocyte apoptosis during heart failure were examined using the antioxidant
      N-acetylcysteine (NAC). Heart failure was established in Japanese white rabbits
      with intravenous injections of doxorubicin, with ten rabbits serving as a control
      group. Of the rabbits with heart failure, 12 were not treated (HF group) and 13
      received NAC (NAC group). Cardiac function was assessed using echocardiography
      and hemodynamic analysis. Myocardial cell apoptosis, apoptosis-related protein
      expression, NF-kappaBp65 expression and activity, total anti-oxidative capacity
      (tAOC), 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) expression and glutathione
      (GSH) expression levels were determined. In the HF group, reduced tAOC, GSH
      levels and Bcl-2/Bax ratios as well as increased 8-iso-PGF2alpha levels and
      apoptosis were observed (all P<0.05), which were effects that were attenuated by
      the treatment with NAC. NF-kappaBp65 and iNOS levels were significantly higher
      and the P-IkappaB-alpha levels were significantly lower in the HF group;
      expression of all three proteins returned to pre-HF levels following treatment
      with NAC. Myocardial cell apoptosis was positively correlated with left
      ventricular end-diastolic pressure (LVEDP), NF-kappaBp65 expression and 8-iso
      PGF2alpha levels, but negatively correlated with the maximal and minimal rates of
      increase in left ventricular pressure (+dp/dtmax and -dp/dtmin, respectively) and
      the Bcl-2/Bax ratio (all P<0.001). The 8-iso-PGF2alpha levels were positively
      correlated with LVEDP and negatively correlated with +dp/dtmax and -dp/dtmin (all
      P<0.001). The present study demonstrated that NAC increased the antioxidant
      capacity, decreased the NF-kappaB activation and reduced myocardial cell
      apoptosis in an in vivo heart failure model. 

PMID- 24889423
TI  - Doctor who offered to arrange female genital mutilation is struck off.

PMID- 24889425
TI  - Systemic inflammatory response syndrome after cardiac surgery: time for a change.

PMID- 24889426
TI  - Harm of in utero tobacco smoke exposure: a heritable trait?

PMID- 24889424
TI  - A genomic island integrated into recA of Vibrio cholerae contains a divergent
      recA and provides multi-pathway protection from DNA damage.
AB  - Lateral gene transfer (LGT) has been crucial in the evolution of the cholera
      pathogen, Vibrio cholerae. The two major virulence factors are present on two
      different mobile genetic elements, a bacteriophage containing the cholera toxin
      genes and a genomic island (GI) containing the intestinal adhesin genes. Non
      toxigenic V. cholerae in the aquatic environment are a major source of novel DNA
      that allows the pathogen to morph via LGT. In this study, we report a novel GI
      from a non-toxigenic V. cholerae strain containing multiple genes involved in DNA
      repair including the recombination repair gene recA that is 23% divergent from
      the indigenous recA and genes involved in the translesion synthesis pathway. This
      is the first report of a GI containing the critical gene recA and the first
      report of a GI that targets insertion into a specific site within recA. We show
      that possession of the island in Escherichia coli is protective against DNA
      damage induced by UV-irradiation and DNA targeting antibiotics. This study
      highlights the importance of genetic elements such as GIs in the evolution of V.
      cholerae and emphasizes the importance of environmental strains as a source of
      novel DNA that can influence the pathogenicity of toxigenic strains. 

PMID- 24889427
TI  - Sex differences in response to pulmonary arterial hypertension therapy: is what's
      good for the goose, good for the gander?

PMID- 24889429
TI  - Expert consensus on advanced critical care echocardiography: opportunity to do it
      right.

PMID- 24889428
TI  - Genetic discovery, rigorous statistics, and pandemic influenza.

PMID- 24889431
TI  - Point: Should storefront clinics provide case finding and chronic care for COPD?
      Yes.

PMID- 24889432
TI  - Counterpoint: Should storefront clinics provide case finding and chronic care for
      COPD? No.

PMID- 24889433
TI  - Rebuttal from Drs. Enright and Nevin.

PMID- 24889434
TI  - Rebuttal from Dr. Celli.

PMID- 24889435
TI  - Chronic pleuropulmonary fibrosis and elastosis of aged donkeys: similarities to
      human pleuroparenchymal fibroelastosis.
AB  - BACKGROUND: Donkey pulmonary fibrosis (DPF) is a spontaneous syndrome of aged
      donkeys with a high prevalence (35%). No previous detailed characterization of
      DPF has been performed. We sought to determine the similarities between DPF and
      recognized patterns of human pulmonary fibrosis. METHODS: Whole lungs were
      collected from 32 aged donkeys at routine necropsy. Gross examination revealed
      pulmonary fibrosis in 19 donkeys (DPF cases), whereas 13 (control cases) had
      grossly normal lungs. Eighteen whole inflated ex vivo lungs (11 DPF cases, seven
      control cases) were imaged with high-resolution CT (HRCT) scan, whereas the
      remainder were sectioned and photographed. Tissue samples were collected from all
      lungs for histopathologic evaluation using a standardized protocol. HRCT images
      and histology sections underwent independent blinded review. Lung tissue was
      analyzed for herpes virus, fungal hyphae, mycobacteria, and dust content.
      RESULTS: Ten of 19 DPF lungs were categorized as being consistent with
      pleuroparenchymal fibroelastosis (PPFE) according to previously defined
      histologic and imaging criteria. All 10 PPFE-like lungs had marked pleural and
      subpleural fibrosis, predominantly within the upper lung zone, with accompanying
      intraalveolar fibrosis and elastosis. Asinine herpesvirus was ubiquitously
      expressed within control and DPF lung tissue. No other etiologic agents were
      identified. CONCLUSIONS: Many cases of DPF share key pathologic and imaging
      features with human PPFE, a rare interstitial pneumonia. Consequently, further
      study of DPF may help to elucidate the etiopathogenesis of human PPFE.

PMID- 24889437
TI  - Clinical and financial considerations for implementing an ICU telemedicine
      program.
AB  - As the population in the United States increases and ages, the need to provide
      high-quality, safe, and cost-effective care to the most critically ill patients
      will be of great importance. With the projected shortage of intensivists,
      innovative changes to improve efficiency and increase productivity will be
      necessary. Telemedicine programs in the ICUs (tele-ICUs) are a successful
      strategy to improve intensivist access to critically ill patients. Although
      significant capital and maintenance costs are associated with tele-ICUs, these
      costs can be offset by indirect financial benefits, such as decreased length of
      stay. To achieve the positive clinical outcomes desired, tele-ICUs must be
      carefully designed and implemented. In this article, we discuss the clinical
      benefits of tele-ICUs. We review the financial considerations, including direct
      and indirect reimbursement and development and maintenance costs. Finally, we
      review design and implementation considerations for tele-ICUs. 

PMID- 24889438
TI  - Small airway-centered granulomatosis caused by long-term exposure to
      polytetrafluoroethylene.
AB  - To date, there have been no reports of chronic pulmonary granulomatosis
      associated with exposure to polytetrafluoroethylene (PTFE). Here, we report three
      cases of small airway-centered granulomatous lesions in workers employed at
      facilities that apply coatings to pans and other utensils. The workers were
      repeatedly exposed to PTFE particles that were probably generated by the drying
      process when PTFE coatings are dried in a convection oven at high temperatures
      (380-420  degrees C). The duration of inhalational PTFE exposure was between 7
      and 20 years. We found granulomatous lung lesions around the small airways in
      lung biopsy specimens obtained from the workers. Scanning electron
      microscopy/energy-dispersive x-ray spectroscopy analysis was performed focusing
      on areas where the PTFE particles were suspected to be located in macrophages.
      The scanning electron microscopy/energy-dispersive x-ray spectroscopy analyses
      revealed fluorine in the particles. Lung tissue samples from all cases were
      analyzed using a fully automated Fourier transform infrared spectrometer.
      Analysis of the spectrum extracted from the position of the foreign particles
      enabled precise identification of the foreign bodies as PTFE. Fourier transform
      infrared revealed that all of the lung tissue samples had bands at 1,202 to 1,148
      cm(-1) and 1,202 to 1,146 cm(-1), which are characteristic of the asymmetric and
      symmetric stretching vibrations of the C-F bonds of PTFE. These cases suggest
      that recurrent inhalational exposure to PTFE particles causes chronic pulmonary
      granulomatosis.

PMID- 24889436
TI  - An official American Thoracic Society/American College of Chest Physicians policy
      statement: the Choosing Wisely top five list in adult pulmonary medicine.
AB  - The American Board of Internal Medicine Foundation's Choosing Wisely campaign
      aims to curb health-care costs and improve patient care by soliciting lists from
      medical societies of the top five tests or treatments in their specialty that are
      used too frequently and inappropriately. The American Thoracic Society (ATS) and
      American College of Chest Physicians created a joint task force, which produced a
      top five list for adult pulmonary medicine. Our top five recommendations, which
      were approved by the executive committees of the ATS and American College of
      Chest Physicians and published by Choosing Wisely in October 2013, are as
      follows: (1) Do not perform CT scan surveillance for evaluation of indeterminate
      pulmonary nodules at more frequent intervals or for a longer period of time than
      recommended by established guidelines; (2) do not routinely offer pharmacologic
      treatment with advanced vasoactive agents approved only for the management of
      pulmonary arterial hypertension to patients with pulmonary hypertension resulting
      from left heart disease or hypoxemic lung diseases (groups II or III pulmonary
      hypertension); (3) for patients recently discharged on supplemental home oxygen
      following hospitalization for an acute illness, do not renew the prescription
      without assessing the patient for ongoing hypoxemia; (4) do not perform chest CT
      angiography to evaluate for possible pulmonary embolism in patients with a low
      clinical probability and negative results of a highly sensitive D-dimer assay;
      (5) do not perform CT scan screening for lung cancer among patients at low risk
      for lung cancer. We hope pulmonologists will use these recommendations to
      stimulate frank discussions with patients about when these tests and treatments
      are indicated--and when they are not.

PMID- 24889439
TI  - A novel treatment approach to H-type esophageal lung in presence of pulmonary
      artery sling with pneumonectomy and intrathoracic tissue-expander placement.
AB  - Congenital tracheal anomalies occur in 1:10,000 births and can be associated with
      congenital cardiac disease. This patient presented with right mainstem atresia,
      right bronchoesophageal fistula without esophageal atresia (H-type esophageal
      lung), and left pulmonary arterial (PA) sling. Taking this into consideration,
      surgical management included right pneumonectomy and placement of expandable
      prosthesis into the thoracic cavity to buttress the mediastinum and prevent
      tracheal deviation-induced kinking of the PA sling, which provided pulmonary
      blood flow to the remaining functional lung. To our knowledge, this is the first
      reported case of esophageal lung in conjunction with a PA sling, as well as the
      first documented use of an expandable prosthesis to prevent acute
      postpneumonectomy syndrome. This case can provide clinicians with increased
      clinical knowledge for treatment of this rare and potentially lethal combination
      of congenital anomalies. 

PMID- 24889440
TI  - Early management of severe sepsis: concepts and controversies.
AB  - Sepsis is among the most common reasons for admission to ICUs throughout the
      world, and it is believed to be the third most common cause of death in the
      United States. The pathogenetic mechanism and physiologic changes associated with
      sepsis are exceedingly complex, but our understanding is evolving rapidly. The
      major pathophysiologic changes in patients with septic shock include vasoplegic
      shock (distributive shock), myocardial depression, altered microvascular flow,
      and a diffuse endothelial injury. These pathophysiologic changes play a central
      role in the management of sepsis. The early management of patients with severe
      sepsis and septic shock centers on the administration of antibiotics, IV fluids,
      and vasoactive agents, followed by source control. However, the specific approach
      to the resuscitation of patients with septic shock remains highly controversial.
      This review provides a practical and physiologic-based approach to the early
      management of sepsis and explores the controversies surrounding the management of
      this complex condition. 

PMID- 24889441
TI  - A 79-year-old woman with bilateral cavitating lung nodules.

PMID- 24889442
TI  - A man in his 40s with frequent bronchitis, localized wheezes, and hemoptysis.

PMID- 24889447
TI  - A multidisciplinary approach is key to the development of critical care medicine
      in mainland china.

PMID- 24889448
TI  - Pulmonary and critical care medicine in China.

PMID- 24889449
TI  - Response.

PMID- 24889450
TI  - Hemoptysis: deja vu for cryoballoon use for pulmonary vein isolation for atrial
      fibrillation ablation.

PMID- 24889451
TI  - Too much testing?

PMID- 24889452
TI  - Response.

PMID- 24889453
TI  - Simple cause for a "complex" problem.

PMID- 24889454
TI  - Response.

PMID- 24889455
TI  - GI symptoms in patients with COPD.

PMID- 24889456
TI  - Quality of life and parental adjustment in pediatric pulmonary hypertension: some
      methodologic considerations.

PMID- 24889457
TI  - Response.

PMID- 24889458
TI  - 6-minute walk distance: effect of instructions.

PMID- 24889459
TI  - Response.

PMID- 24889460
TI  - Anticytokeratin (CAM5.2) reagent identifies cytokeratins 7 and 8, not cytokeratin
      18.

PMID- 24889461
TI  - Response.

PMID- 24889462
TI  - A man in his 40s with fever and hypotension.

PMID- 24889466
TI  - The virtue of defects: stable bromine production by catalytic oxidation of
      hydrogen bromide on titanium oxide.
AB  - Rutile TiO2 is a heavily investigated oxide with, to date, scarce applications in
      industrial catalysis. The inactivity of this material in oxidations has been
      related to its inability to dissociate molecular oxygen. Herein we show how
      rutile catalyzes the oxidation of HBr to Br2 through defect states that are
      introduced during the reaction. The identification of active, stable, and
      abundant materials for bromine production is key to the future implementation of
      Br2-mediated alkane functionalization processes. The catalytic properties of TiO2
      are discussed in comparison to expensive rutile-type oxides, such as RuO2 and
      IrO2, on the basis of surface characterization and molecular modeling.

PMID- 24889467
TI  - Reverse transcription through a bulky triazole linkage in RNA: implications for
      RNA sequencing.
AB  - A triazole linkage is formed in RNA by untemplated strain-promoted or CuAAC
      chemical ligation of 3'-azide and 5'-cyclooctyne oligonucleotides under
      denaturing conditions. Reverse transcriptase reads through these artificial
      linkages with omission of one nucleotide. These surprising results have
      implications for RNA isolation, amplification, sequencing and a variety of
      biological applications. 

PMID- 24889469
TI  - Repetitive narrow and broad beats causing mild LV impairment: what is the
      mechanism?

PMID- 24889470
TI  - Coordination and redox isomerization in the reduction of a uranium(III) monoarene
      complex.
AB  - Synthetic studies on the redox chemistry of trivalent uranium monoarene complexes
      were undertaken with a complex derived from the chelating tris(aryloxide)arene
      ligand ((Ad,Me) ArO)3 mes(3-) . Cyclic voltammetry of [{((Ad,Me) ArO)3 mes}U(III)
      ] (1) revealed a nearly reversible and chemically accessible reduction at -2.495
      V vs. Fc/Fc(+) -the first electrochemical evidence for a formally divalent
      uranium complex. Chemical reduction of 1 indicates that reduction induces
      coordination and redox isomerization to form a uranium(IV) hydride, and addition
      of a crown ether results in hydride insertion into the coordinated arene to
      afford uranium(IV) complexes. This stoichiometric reaction sequence provides
      structural insight into the mechanism of arene functionalization at diuranium
      inverted sandwich complexes. 

PMID- 24889471
TI  - Hidden costs of poor image quality: a radiologist's perspective.
AB  - Although image quality is a well-recognized component in the successful delivery
      of medical imaging services, it has arguably declined over the past decade owing
      to several technical, economic, cultural, and geographic factors. To improve
      quality, the radiologist community must take a more proactive role in image
      quality analysis and optimization; these require analysis of not just the single
      step of image acquisition but the entire imaging chain. Radiologists can benefit
      through improved report accuracy, diagnostic confidence, and workflow efficiency.
      The derived data-driven analyses offer an objective means for provider
      performance analysis, which can help combat commoditization trends and self
      referral by nonradiologist providers. 

PMID- 24889468
TI  - Making decisions about chronic disease treatment: a comparison of parents and
      their adolescent children.
AB  - OBJECTIVE: To compare factors considered by parents to those considered by
      adolescents making decisions about chronic disease treatments. METHODS: We
      conducted individual interviews with 15 parent-adolescent dyads in which the
      adolescent had either juvenile idiopathic arthritis or Crohn's disease. Questions
      focused on treatment decisions, with an emphasis on the factors that influenced
      each individual's preferences related to biologic therapies. A multidisciplinary
      team developed a coding structure. All interviews were coded by two people with
      disagreements resolved through discussion. We used content analysis and coding
      matrices to examine decision factors within and between parent-adolescent dyads.
      RESULTS: Parents and adolescents both participated in decisions about treatment
      with biologic therapies but considered decision factors differently. In only half
      of cases did parents and adolescents agree on the factor that most influenced
      their decision. Although their decision factors often fell into similar
      categories (e.g. treatment risks, quality of life), in many cases the specifics
      varied between adolescents and their parents. Adolescents were more likely to
      focus on immediate treatment effects and quality of life while parents took a
      longer term view of the decision. Agreement within dyads was most consistent when
      a special circumstance influenced the treatment decision. CONCLUSIONS:
      Differences regarding influential decision factors exist within parent-adolescent
      dyads. Continued research is needed to determine the extent to which such
      differences are due to individual preferences or to variations in the information
      available to each person. Future decision support interventions will need to
      address parents' and adolescents' potentially disparate views and information
      needs.

PMID- 24889472
TI  - Obamacare and fee-for-service.

PMID- 24889473
TI  - A simple method to visualize image quality degradation for off-center regions in
      open-configuration MR systems.

PMID- 24889474
TI  - Taxi driver or bank clerk?

PMID- 24889475
TI  - Comparison of image-guided nonfocal hepatic biopsies performed by physicians and
      nurse midlevel providers.
AB  - Image-guided hepatic biopsies have been performed safely and accurately for a
      number of years. The advantages of sonographic or CT guidance in avoiding major
      vital structures, such as large vessels, the gallbladder, or pleura, have been
      confirmed many times. However, the safety and accuracy of certified nurse
      practitioners' performing these biopsies have not been described. The authors
      describe a retrospective review of 418 image-guided hepatic biopsies that
      demonstrated no significant difference in accuracy or complication rates between
      biopsies performed by certified nurse practitioners and those performed by
      radiologists in a single-institution, multihospital academic setting.
      Appropriately trained advanced practice providers can perform image-guided
      hepatic biopsies safely and accurately. 

PMID- 24889476
TI  - Lessons learned from reviewing breast imaging malpractice cases.

PMID- 24889477
TI  - Evidence for diagnostic imaging guidelines.

PMID- 24889478
TI  - Optimizing modality operations.

PMID- 24889480
TI  - New and established treatment options for mycosis fungoides and Sezary syndrome -
      an update.
AB  - At the time of diagnosis primary cutaneous lymphomas are limited to the skin. T
      cell lymphomas represent at least two thirds of all primary cutaneous lymphomas
      with mycosis fungoides and Sezary syndrome being the most frequent entities. A
      precise staging based on clinical, histological, immunohistological and molecular
      biological criteria is crucial for selecting the appropriate therapy. Since
      curative treatment is only possible in exceptional cases, the aim of any therapy
      is to achieve healing of the skin lesions, minimizing relapses, preventing
      progression and maintaining the quality of life. While in early disease stages
      skin-directed therapy is being used, in later stages systemic treatments become
      more important. This work aims to provide an overview of established and new
      therapies for the treatment of mycosis fungoides and Sezary syndrome. 

PMID- 24889479
TI  - Geographic access to breast imaging for US women.
AB  - PURPOSE: The breast imaging modalities of mammography, ultrasound, and MRI are
      widely used for screening, diagnosis, treatment, and surveillance of breast
      cancer. Geographic access to breast imaging services in various modalities is not
      known at a national level overall or for population subgroups. METHODS: A
      retrospective study of 2004-2008 Medicare claims data was conducted to identify
      ZIP codes in which breast imaging occurred, and data were mapped. Estimated
      travel times were made for each modality for 215,798 census block groups in the
      contiguous United States. Using Census 2010 data, travel times were characterized
      by sociodemographic factors for 92,788,909 women aged >=30 years, overall, and by
      subgroups of age, race/ethnicity, rurality, education, and median income.
      RESULTS: Overall, 85% of women had travel times of <=20 minutes to nearest
      mammography or ultrasound services, and 70% had travel times of <=20 minutes for
      MRI with little variation by age. Native American women had median travel times 2
      3 times longer for all 3 modalities, compared to women of other racial/ethnic
      groups. For rural women, median travel times to breast imaging services were 4-8
      fold longer than they were for urban women. Black and Asian women had the
      shortest median travel times to services for all 3 modalities. CONCLUSIONS:
      Travel times to mammography and ultrasound breast imaging facilities are short
      for most women, but for breast MRI, travel times are notably longer. Native
      American and rural women are disadvantaged in geographic access based on travel
      times to breast imaging services. This work informs potential interventions to
      reduce inequities in access and utilization.

PMID- 24889485
TI  - 25-hydroxyvitamin D and increased all-cause mortality in very old women: the
      Newcastle 85+ study.
AB  - OBJECTIVE: To investigate the associations between low and high concentrations of
      baseline serum 25-hydroxyvitamin D [25(OH)D] and all-cause mortality in very old
      (>=85 years) men and women over 6 years. DESIGN, SETTING AND SUBJECTS:
      Prospective mortality data from 775 participants in the Newcastle 85+ Study were
      analysed for survival in relation to 25(OH)D (season-specific quartiles and
      predefined cut-off values) and sex using Cox proportional hazards models. The
      models were fitted to the entire and restricted (nonusers of vitamin D-containing
      supplements and medication) cohorts. RESULTS: For the entire cohort, mortality
      was higher in both the lowest and highest 25(OH)D season-specific quartiles [SQ1:
      hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01-1.69, P = 0.04; SQ4: HR
      1.44, 95% CI 1.12-1.85, P = 0.004] compared with the combined middle quartiles
      (SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk
      for the highest quartile remained significant after further adjustment for
      lifestyle variables (SQ4: HR 1.37, 95% CI 1.06-1.77, P = 0.02) and was seen only
      in women in sex-specific analyses. Similarly, in sensitivity analyses with
      predefined 25(OH)D cut-off values, the highest 25(OH)D concentration (>=75 nmol
      L(-1) ) was associated with a 2.4-fold increased risk of mortality in women
      (restricted cohort) after adjusting for all covariates. CONCLUSION: Low and high
      season-specific 25(OH)D quartiles were associated with increased risks of
      mortality over 6 years in the very old; this effect was particularly noticeable
      in women, including those who reported taking vitamin D-containing
      supplements/medication.

PMID- 24889486
TI  - A retrospective comparison of microwave ablation vs. radiofrequency ablation for
      colorectal cancer hepatic metastases.
AB  - BACKGROUND: Microwave (MWA) and radiofrequency ablation (RFA) are the most
      commonly used techniques for ablating colorectal-liver metastases (CRLM). The
      technical and oncologic differences between these modalities are unclear.
      METHODS: We conducted a matched-cohort analysis of patients undergoing open MWA
      or RFA for CRLM at a tertiary-care center between 2008 and 2011; the primary
      endpoint was ablation-site recurrence. Tumors were matched by size, clinical-risk
      score, and arterial-intrahepatic or systemic chemotherapy use. Outcomes were
      compared using conditional logistic regression and stratified log-rank test.
      RESULTS: We matched 254 tumors (127 per group) from 134 patients. MWA and RFA
      groups were comparable by age, gender, median number of tumors treated, proximity
      to major vessels, and postoperative complication rates. Patients in the MWA group
      had lower ablation-site recurrence rates (6% vs. 20%; P < 0.01). Median follow
      up, however, was significantly shorter in the MWA group (18 months [95%
      confidence interval 17-20] vs. 31 months [95% confidence interval 28-35]; P <
      0.001). Kaplan-Meier estimates of ablation-site recurrence at 2 years were
      significantly lower for the lesions treated with MWA (7% vs. 18%, P: 0.01).
      CONCLUSIONS: Ablation-site recurrences of CRLM were lower with MWA compared with
      RFA in this matched cohort analysis. Longer follow-up time in the MWA may
      increase the recurrence rate; however, actuarial local failure estimations
      demonstrated better local control with MWA.

PMID- 24889487
TI  - Clinical aggressiveness of myxofibrosarcomas associates with down-regulation of
      p12CDK2AP1: prognostic implication of a putative tumor suppressor that induces
      cell cycle arrest and apoptosis via mitochondrial pathway.
AB  - BACKGROUND: Attenuated endogenous protein levels of cyclin-dependent kinase 2
      associated protein 1 (p12(CDK2AP1)) and its active homodimer p25(CDK2AP1) were
      found in myxofibrosarcoma-derived cell lines. Clinical and biological
      significances of this putative tumor suppressor in myxofibrosarcoma were studied.
      METHODS: Plasmids carrying the CDK2AP1 gene and small hairpin RNA interference
      (shRNAi) targeting CDK2AP1 were transfected into NMFH-1 and/or OH931 cells to
      evaluate the effects on the CDK2, active caspase 3 (CASP3), cleaved-CASP8 and 
      CASP9 levels, cell cycle regulation, and/or apoptotic responses. Immunostaining
      of p12(CDK2AP1) was interpretable in 102 primary myxofibrosarcomas and correlated
      with clinicopathological variables, CDK2, Ki-67 and active CASP3 protein levels,
      and disease-specific survival. RESULTS: Exogenous expression of p12(CDK2AP1) in
      NMFH-1 and OH931 cells significantly induced G0/G1 cell cycle arrest and down
      regulated CDK2 protein level. In NMFH-1 cells, these aspects were reversed by
      shRNAi targeting CDK2AP1 gene. Increased active CASP3 and cleaved-CASP9, but not 
      CASP8, were detected after CDK2AP1 overexpression, suggesting the cellular
      apoptosis were induced through the mitochondrial pathway. Immunostains of
      p12(CDK2AP1) were aberrantly decreased in 56.9 % of cases; positively and
      negatively correlated with protein levels of CDK2 (p = 0.023), Ki-67 (p = 0.001)
      and active CASP3 (p < 0.001), respectively. Following by high histological
      grades, p12(CDK2AP1) down-regulation was predictive of worse disease-specific
      survival in univariate (p = 0.003) and multivariate (p = 0.004) analyses.
      CONCLUSIONS: Through down-regulation of CDK2, high p12(CDK2AP1) level induced
      cell cycle arrest and the mitochondrial-dependent apoptotic pathway. Low
      p12(CDK2AP1) level represents a poor prognostic factor in patients with
      myxofibrosarcoma.

PMID- 24889488
TI  - KRAS mutation is associated with worse prognosis in stage III or high-risk stage
      II colon cancer patients treated with adjuvant FOLFOX.
AB  - BACKGROUND: Although KRAS mutation has a predictive role in stage IV colorectal
      cancer (CRC) patients treated with anti-EGFR therapy, there have been
      controversies in the prognostic impact of KRAS mutation in stage II or III
      disease. The purpose of this study was to assess the prognostic impact of KRAS
      and BRAF mutation in patients treated with adjuvant 5
      fluorouracil/leucovorin/oxaliplatin (FOLFOX). METHODS: KRAS exon 2 and BRAF codon
      600 were analyzed in patients with stage II and III CRC who underwent curative
      resection followed by adjuvant FOLFOX. Clinicopathologic features and disease
      free survival (DFS) were compared. RESULTS: Among a total of 437 patients,
      mutational data of KRAS and BRAF were available in 388 and 433 patients,
      respectively. KRAS mutation (codon 12 and 13) and BRAF V600E mutation was found
      in 26.5 and 3.7 % of patients. DFS was significantly worse in the KRAS mutant
      patients compared to KRAS wild type patients (3-year DFS 79 and 92 %, p = 0.006).
      Multivariate analysis revealed KRAS mutation as an independent negative
      prognostic factor for DFS (adjusted hazard ratio 2.30, 95 % confidence interval
      1.23-4.32). Among the various subtypes of KRAS mutation, G13D (3-year DFS 76 %, p
      = 0.008) was significantly associated with poor DFS, while G12D was not
      associated with prognosis (3-year DFS 86 %, p = 0.61). There was no association
      between BRAF mutation and DFS. CONCLUSIONS: KRAS mutation has an adverse
      prognostic impact on stage II or III CRC treated with adjuvant FOLFOX.

PMID- 24889490
TI  - In vivo evaluation of lateral lipid chain packing in human stratum corneum.
AB  - BACKGROUND/AIMS: The matrix of intercellular lipids (ICL) of stratum corneum (SC)
      plays an important role in the barrier function of SC. It is important to
      understand the structure of the ICL matrix for dermatology and cosmetic science.
      Several methods exist for the analysis of the structure; however, it is difficult
      to conduct these analyses noninvasively. METHODS: We have developed a method for
      the analysis of the lateral packing of ICL using Raman spectroscopy. As a proof
      of-principle experiment, we prepared a human SC sheet sample and analyzed its
      structure by the proposed method and by a conventional method involving X-ray
      diffraction. We compared the results of both methods. In addition, we applied the
      proposed method to living human skin, and we analyzed the lateral packing of ICL
      of SC taken from three separate body sites. RESULTS: The results of our method
      corresponded to those of the conventional method. We detected regional
      differences of ICL lateral packing using our method in vivo. The results
      indicated that the packing of ICL in SC taken from the forearm and upper arm are
      more ordered than that taken from the cheek. CONCLUSION: The results verify that
      our developed method allows the evaluation of the lateral packing of ICL inside
      the SC layer of the skin in vivo. Using this method, we can detect regional
      differences of SC samples taken from various body sites.

PMID- 24889489
TI  - Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and
      identifying therapeutic targets.
AB  - BACKGROUND: The molecular alterations that drive tumorigenesis in intrahepatic
      cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the
      incidence and prognostic significance of mutations associated with ICC among
      patients undergoing surgical resection. METHODS: Multiplexed mutational profiling
      was performed using nucleic acids that were extracted from 200 resected ICC tumor
      specimens from 7 centers. The frequency of mutations was ascertained and the
      effect on outcome was determined. RESULTS: The majority of patients (61.5 %) had
      no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic
      mutation, only a small number of gene mutations were identified with a frequency
      of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified
      in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %),
      TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients
      with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent
      PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in
      IDH1 and KRAS were noted. Compared with ICC tumors that had no identified
      mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while
      KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio
      6.51) (both P < 0.05). Although clinicopathological features such as tumor number
      and nodal status were associated with survival, no specific mutation was
      associated with prognosis. CONCLUSIONS: Most somatic mutations in resected ICC
      tissue are found at low frequency, supporting a need for broad-based mutational
      profiling in these patients. IDH1 and KRAS were the most common mutations noted.
      Although certain mutations were associated with ICC clinicopathological features,
      mutational status did not seemingly affect long-term prognosis.

PMID- 24889491
TI  - Functional and return to work outcomes following major trauma involving severe
      pelvic ring fracture.
AB  - BACKGROUND: There is limited evidence describing the long-term outcomes of severe
      pelvic ring fractures. The aim of this study was to describe the longer term
      independent living and return to work outcomes following severe pelvic ring
      fracture. METHODS: Adult survivors to discharge from two major trauma centres
      with AO/Tile type B and C fractures were followed up at 6, 12 and 24-months post
      injury to capture functional (Glasgow Outcome Scale-Extended [GOS-E]) and return
      to work data. Multivariable, mixed effects models were used to identify
      predictors of outcome. RESULTS: A total of 111 of 114 (97%) cases were followed
      up. The mean (SD) age of participants was 41.9 (18.9) years, 77% were male, 81%
      were transport-related and 90% were multi-trauma patients. Further, 11% were
      managed conservatively, 10% with external fixation and 79% with open reduction
      and internal fixation. At 24 months, 77% were living independently (GOS-E > 4)
      and 59% had returned to work. Higher Injury Severity Scores (ISS) were associated
      with lower risk-adjusted odds of return to work (P = 0.04) and independent living
      (P = 0.06). Post-operative infection was associated with living independently (P
      = 0.02). CONCLUSION: Despite the severity of the injuries sustained, 77% of
      severe pelvic ring fracture patients were living independently and 59% had
      returned to work, 2-years post-injury. Fracture type and management were not key
      predictors of outcome. Large-scale multi-centre studies are needed to fully
      understand the burden of severe pelvic ring fractures and to guide clinical
      management.

PMID- 24889492
TI  - Fractional laser for vitiligo treated by 10,600 nm ablative fractional carbon
      dioxide laser followed by sun exposure.
AB  - BACKGROUND: Vitiligo is an acquired disorder of the skin and mucous membranes.
      Many patients with vitiligo remain in the refractory state despite the
      availability of numerous potential treatments. To the best of our knowledge, only
      one trial considers ablative fractional CO2 laser in the treatment of vitiligo.
      OBJECTIVE: To investigate the effects of fractional CO2 laser followed by
      systemic sun exposure on non-segmental vitiligo (NSV). METHODS: Ten patients
      presenting refractory NSV were enrolled in this study. The patients underwent
      three sessions, one month apart, of fractional CO2 laser therapy on the affected
      areas of the skin (L-group). Five days after each laser treatment, patients were
      asked to expose themselves to the sun for 2 hours on a daily basis. Objective and
      subjective clinical assessments were performed at the beginning and at the end of
      the treatment. The L-group was then compared to a control group (C-group) that
      consisted of vitiligo lesions in the same patients but with sun exposure as the
      exclusive therapy. RESULTS: Compared to the C-group, the L-group showed better
      improvement in both objective and subjective assessments. There were no
      noticeable adverse events in terms of scarring and Koebner phenomenon among
      others. CONCLUSIONS: All patients treated with both, laser sessions and sun
      exposure, improved their chronic NSV lesions. Improvement was less significant in
      patients who exhibited vitiligo lesions over articular surfaces such as elbows
      and underarms. The best results were observed in vitiligo plaques located on the
      face, neck and legs. Consequently, fractional CO2 laser followed by sun exposure
      could be considered as an alternative modality for the treatment of refractory
      vitiligo, especially in sunny regions.

PMID- 24889493
TI  - Reply: To PMID 23952253.

PMID- 24889494
TI  - Palladium-catalyzed intramolecular reductive cross-coupling of Csp2-Csp3 bond
      formation.
AB  - A Pd-catalyzed efficient reductive cross-coupling reaction without metallic
      reductant to construct a Csp(2) -Csp(3) bond has been reported. A Pd(IV) complex
      was proposed to be a key intermediate, which subsequently went through double
      oxidative addition and double reductive elimination to produce the cross-coupling
      products by involving Pd(0/II/IV) in one transformation. The oxidative addition
      from Pd(II) to Pd(IV) was partially demonstrated to be a radical process by self
      oxidation of substrate without additional oxidants. Furthermore, the solvent was
      proved to be the reductant for this transformation through XPS analysis.

PMID- 24889495
TI  - Association of reflux symptom index scores with gastroesophageal flap valve
      status.
AB  - OBJECTIVE: Gastroesophageal reflux disease is a chronic symptom of mucosal damage
      caused by gastric acid reflux. Impaired gastroesophageal flap valve (GEFV) is one
      of the common etiologic factors of gastroesophageal reflux. The aim of this study
      was to investigate the association between GEFV, RSI, and GER in patients who
      underwent gastroesophageal endoscopy. METHODS: Two hundred and fifty seven
      consecutive patients with reflux symptoms (151 men and 106 women, mean age was
      50.22 years) who underwent routine upper gastrointestinal endoscopy were enrolled
      to our study. GEFV was graded as I through IV according to the Hill's
      classification. Symptoms of laryngopharyngeal and upper gastrointestinal disease
      and endoscopic severity of esophageal injury were correlated with GEFV status.
      The GEFV was classified into two groups: normal GEFV group (grade I) and the
      abnormal GEFV group (grades II-III and IV). The reflux symptom index (RSI) was
      used as a diagnostic tool for LPR. RESULTS: Age, male gender, and body mass index
      were significantly related to an abnormal GEFV. The rate of abnormal grades of
      GEFV (Grade II+III+IV) was 31%. Age of normal and abnormal grades of GEFV
      (49.0/50.8 vs 52.9) and values of BMI (26.2/26.7 vs 26.5) were similar. RSI
      scores were correlated with gastroesophageal flap valve grades but RSI scores
      were not correlated with Los Angeles gastroesophageal reflux (GER)
      Classification. Moreover, gastroesophageal reflux grade of Los Angeles
      Classification was positively correlated with gastroesophageal flap valve grades.
      CONCLUSION: Endoscopic grading of GEFV is a simple and useful technique which may
      provide an accurate diagnosis of laryngopharyngeal and gastroesophageal reflux.
      Also, reflux symptom index (RSI) is a simple, economic and noninvasive diagnostic
      tool for gastroesophageal reflux. However, in this research, we did not find any
      correlation between reflux symptom index and degree of esophageal mucosal injury
      which was classified according to LA classification.

PMID- 24889496
TI  - Relationships between exposure and dose in aquatic toxicity tests for organic
      chemicals.
AB  - There is continuing debate about the merits of exposure-based toxicity metrics
      such as median lethal concentration (LC50) versus organism-based metrics such as
      critical body residue (CBR) as indicators of chemical toxicity to aquatic
      organisms. To demonstrate relationships and differences between these 2 metrics,
      the authors applied a simple one-compartment toxicokinetic mass-balance model for
      water-exposed fish for a series of hypothetical organic chemicals exhibiting
      baseline narcotic toxicity. The authors also considered the influence of several
      toxicity-modifying factors. The results showed that the results of standard
      toxicity tests, such as the LC50, are strongly influenced by several modifying
      factors, including chemical and organism characteristics such as hydrophobicity,
      body size, lipid content, metabolic biotransformation, and exposure durations.
      Consequently, reported LC50s may not represent consistent dose surrogates and may
      be inappropriate for comparing the relative toxicity of chemicals. For
      comparisons of toxicity between chemicals, it is preferable to employ a delivered
      dose metric, such as the CBR. Reproducible toxicity data for a specific
      combination of chemical, exposure conditions, and organism can be obtained only
      if the extent of approach to steady state is known. Suggestions are made for
      revisions in test protocols, including the use of models in advance of empirical
      testing, to improve the efficiency and effectiveness of tests and reduce the
      confounding influences of toxicity-modifying factors, especially exposure
      duration and metabolic biotransformation. This will assist in linking empirical
      measurements of LC50s and CBRs, 2 different but related indicators of aquatic
      toxicity, and thereby improve understanding of the large existing database of
      aquatic toxicity test results.

PMID- 24889497
TI  - Topographic specializations in the retinal ganglion cell layer correlate with
      lateralized visual behavior, ecology, and evolution in cockatoos.
AB  - Cockatoos are a unique avian group inhabiting a diversity of arboreal and
      terrestrial microhabitats. Most species display strong lateralized visual
      behaviors using their left eye/foot to assist with food manipulation during
      foraging. In this study, we used retinal wholemounts and stereological methods to
      investigate whether the topographic distribution of retinal ganglion cells in
      cockatoos reflects their lateralized behaviors and microhabitat diversity. We
      found that all species studied possess a horizontal visual streak and a shallow
      central fovea that afford increased spatial resolution in the lateral visual
      field. Arboreal cockatoos have a well-defined dorsotemporal area, in contrast to
      terrestrial cockatoos, in which this specialization is inconspicuous or absent.
      Terrestrial cockatoos also have a triangular extension of increased ganglion cell
      density directed toward the dorsotemporal retinal periphery. Both the
      dorsotemporal area and the triangular extension enhance spatial resolution in the
      frontal and inferior visual fields, which potentially assists with binocular
      coordination during foraging. We found significantly higher ganglion cell
      densities in the left (52,000-72,000 cells/mm2) compared with the right (42,500
      50,000 cells/mm2) perifoveal region of species that have strong left eye-left
      foot lateralized behaviors. In contrast, cockatoo species that show no
      lateralized behaviors have equivalent retinal ganglion cell densities in both
      left and right perifoveal regions (42,500-52,500 cells/mm2). Retinal ganglion
      cell peak densities in the dorsotemporal area showed no significant difference
      between left and right eyes for any species, suggesting that cockatoos use both
      eyes to extract information in the binocular visual field, independent of the
      degree of lateralization.

PMID- 24889498
TI  - The acute brain response to levodopa heralds dyskinesias in Parkinson disease.
AB  - OBJECTIVE: In Parkinson disease (PD), long-term treatment with the dopamine
      precursor levodopa gradually induces involuntary "dyskinesia" movements. The
      neural mechanisms underlying the emergence of levodopa-induced dyskinesias in
      vivo are still poorly understood. Here, we applied functional magnetic resonance
      imaging (fMRI) to map the emergence of peak-of-dose dyskinesias in patients with
      PD. METHODS: Thirteen PD patients with dyskinesias and 13 PD patients without
      dyskinesias received 200mg fast-acting oral levodopa following prolonged
      withdrawal from their normal dopaminergic medication. Immediately before and
      after levodopa intake, we performed fMRI, while patients produced a mouse click
      with the right or left hand or no action (No-Go) contingent on 3 arbitrary cues.
      The scan was continued for 45 minutes after levodopa intake or until dyskinesias
      emerged. RESULTS: During No-Go trials, PD patients who would later develop
      dyskinesias showed an abnormal gradual increase of activity in the
      presupplementary motor area (preSMA) and the bilateral putamen. This
      hyperactivity emerged during the first 20 minutes after levodopa intake. At the
      individual level, the excessive No-Go activity in the predyskinesia period
      predicted whether an individual patient would subsequently develop dyskinesias (p
      < 0.001) as well as severity of their day-to-day symptomatic dyskinesias (p <
      0.001). INTERPRETATION: PD patients with dyskinesias display an immediate
      hypersensitivity of preSMA and putamen to levodopa, which heralds the failure of
      neural networks to suppress involuntary dyskinetic movements.

PMID- 24889500
TI  - The effect of loading on peri-implant bone: a critical review of the literature.
AB  - In the 90s, there was a general belief that mechanical overloading was one of the
      main reasons for late implant failure. This triggered research to assess the role
      of mechanical loading on the establishment and the maintenance of oral implant
      osseointegration. Animal experimental studies indeed suggested the potential
      detrimental effect of excessive mechanical load on peri-implant bone, although
      randomised or controlled clinical trials of treatment interventions of oral
      implants designed to study overload are lacking. The lack of quantification of so
      called overload at the implant level in the intra-oral setting is one of the main
      shortcomings in the literature. The level of evidence of the studies on bone
      response to implant loading is weak and does not indicate that overload can lead
      to peri-implant bone loss, except in case of inflammation. Clinical and animal
      experimental studies on early and immediate implant loading, however, provide
      information on the impact of mechanical loading on the process of
      osseointegration. It is obvious that micromotion between the implant and host
      tissues compromises osseointegration. However, in case of an efficient force
      transfer between implant and surrounding tissues, mechanical loading might even
      stimulate peri-implant bone formation and therefore osseointegration. 

PMID- 24889499
TI  - The effects of bromocriptine treatment during early pregnancy on postpartum
      maternal behaviors in rats.
AB  - Prolactin, a hormone of the anterior pituitary, is involved in initiating
      maternal behavior, alleviating postpartum anxiety, and stimulating lactogenesis.
      Bromocriptine, a dopamine D2 receptor agonist, inhibits prolactin secretion.
      Bromocriptine administration represses postpartum maternal behaviors (pup
      retrieval) in mice, and causes elevated anxiety in the elevated plus maze [Larsen
      & Grattan (2010). Endocrinology 151(8): 3805-3814]. Whether similar effects exist
      in other species is unknown. The present study examined the possible involvement
      of prolactin during early gestation on maternal behavior and anxiety in rats.
      Bromocriptine given on days 2-4 of pregnancy resulted in impaired postpartum
      maternal behaviors in a novel environment during early lactation. However,
      compared to controls, bromocriptine-treated subjects did not exhibit increased
      postpartum anxiety in the elevated plus maze. These findings support work in mice
      that bromocriptine treatment during early gestation impedes postpartum maternal
      care, and indicate that early gestational hormonal status affects postpartum
      behavior more broadly in other mammals.

PMID- 24889501
TI  - Dengue disease surveillance: an updated systematic literature review.
AB  - OBJECTIVES: To review the evidence for the application of tools for dengue
      outbreak prediction/detection and trend monitoring in passive and active disease
      surveillance systems in order to develop recommendations for endemic countries
      and identify important research needs. METHODS: This systematic literature review
      followed the protocol of a review from 2008, extending the systematic search from
      January 2007 to February 2013 on PubMed, EMBASE, CDSR, WHOLIS and Lilacs. Data
      reporting followed the PRISMA statement. The eligibility criteria comprised (i)
      population at risk of dengue, (ii) dengue disease surveillance, (iii) outcome of
      surveillance described and (iv) empirical data evaluated. The analysis classified
      studies based on the purpose of the surveillance programme. The main limitation
      of the review was expected publication bias. RESULTS: A total of 1116 papers were
      identified of which 36 articles were included in the review. Four cohort-based
      prospective studies calculated expansion factors demonstrating remarkable levels
      of underreporting in the surveillance systems. Several studies demonstrated that
      enhancement methods such as laboratory support, sentinel-based reporting and
      staff motivation contributed to improvements in dengue reporting. Additional
      improvements for passive surveillance systems are possible by incorporating
      simple data forms/entry/electronic-based reporting; defining clear system
      objectives; performing data analysis at the lowest possible level (e.g.
      district); seeking regular data feedback. Six studies showed that serotype
      changes were positively correlated with the number of reported cases or with
      dengue incidence, with lag times of up to 6 months. Three studies found that data
      on internet searches and event-based surveillance correlated well with the
      epidemic curve derived from surveillance data. CONCLUSIONS: Passive surveillance
      providing the baseline for outbreak alert should be strengthened and appropriate
      threshold levels for outbreak alerts investigated. Additional enhancement tools
      such as syndromic surveillance, laboratory support and motivation strategies can
      be added. Appropriate alert signals need to be identified and integrated into a
      risk assessment tool. Shifts in dengue serotypes/genotype or electronic event
      based surveillance have also considerable potential as indicator in dengue
      surveillance. Further research on evidence-based response strategies and cost
      effectiveness is needed.

PMID- 24889503
TI  - Attachment-retained gingival prosthesis for implant-supported fixed dental
      prosthesis in the maxilla: a clinical report.
AB  - The rehabilitation of edentulous maxillae is a complex procedure due to the
      involvement of esthetic and functional requirements. A trial maxillary denture
      can be used to identify the need for adequate upper lip support when replacing
      removable complete dentures by implant-fixed dental prostheses. This clinical
      report describes the outcome of the rehabilitation of an edentulous atrophic
      maxilla with unfavorable maxillomandibular relationship and deficient upper lip
      support. A trial denture was fabricated and used to diagnose the need for a
      prosthesis capable of restoring the upper lip support. The reduced upper lip
      support was also confirmed by a lateral cephalogram. The patient was
      rehabilitated by an implant-fixed dental prosthesis associated with an attachment
      retained gingival prosthesis. The case presented shows that when loss of upper
      lip support is detected and the patient does not wish to undergo further surgical
      reconstruction procedure, the retention of a gingival prosthesis using a ball
      attachment is a satisfactory treatment option. 

PMID- 24889504
TI  - Skin reactions amongst Greek endodontists: a national questionnaire survey.
AB  - AIM: To investigate amongst Greek endodontists in the past 5 years the
      prevalence, aetiologic factors, severity and treatment for skin reactions.
      METHODOLOGY: One hundred and 47 endodontists met the inclusion criteria and were
      invited to participate in the survey. Participants were asked for
      personal/professional data, prevalence, aetiologic factors, symptoms, severity
      and treatment for skin reactions in the past 5 years. The type of gloves used and
      frequency of hand washing as well as information on history of atopy and eczema
      were also recorded. Data were analysed using chi-square test and independent
      samples t-test. The level of significance was set at P = 0.05. RESULTS: The
      response rate was 84%. Skin reactions were reported by 32.5% of participants.
      Hands were the body part most frequently affected (66% of cases); glove powder
      accounted for 73% of skin reactions. Medical care was sought by 28.2% of the
      affected participants. Endodontists with a history of atopy (P < 0.001) and
      dermal eczema (P < 0.001) as well as females (P = 0.023) were more likely to
      report skin reactions. Replacement of powdered latex gloves with powder-free or
      vinyl/nitrile gloves, avoidance of potential allergens and use of pharmaceutical
      ointments were adopted by 48.7%, 23.1% and 2.6% of the affected endodontists,
      respectively, to manage skin reactions. CONCLUSIONS: Approximately one-third of
      participants reported skin reactions. History of atopy and dermal eczema as well
      as gender was significantly associated with such reactions. The use of powder
      free latex gloves instead of powdered ones was the measure most frequently
      adopted to manage reactions.

PMID- 24889502
TI  - A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in
      glioma.
AB  - INTRODUCTION: Mutations in isocitrate dehydrogenase genes IDH1 or IDH2 are
      frequent in glioma, and IDH mutation status is a strong diagnostic and prognostic
      marker. Current IDH mutation screening is performed with an immunohistochemistry
      (IHC) assay specific for IDH1 R132H, the most common mutation. Sequencing is
      recommended as a second-step test for IHC-negative or -equivocal cases. We
      developed and validated a new real-time quantitative polymerase chain reaction
      (PCR) assay for single-step detection of IDH1 R132H and 11 rare IDH1/2 mutations
      in formalin-fixed paraffin-embedded (FFPE) glioma samples. Performance of the
      IDH1/2 PCR assay was compared to IHC and Sanger sequencing. RESULTS: The IDH1/2
      PCR assay combines PCR clamping for detection of 7 IDH1 and 5 IDH2 mutations, and
      Amplification Refractory Mutation System technology for specific identification
      of the 3 most common mutations (IDH1 R132H, IDH1 R132C, IDH2 R172K). Analytical
      sensitivity of the PCR assay for mutation detection was <5% for 11/12 mutations
      (mean: 3.3%), and sensitivity for mutation identification was very high (0.8% for
      IDH1 R132H; 1.2% for IDH1 R132C; 0.6% for IDH2 R172K). Assay performance was
      further validated on 171 clinical glioma FFPE samples; of these, 147 samples met
      the selection criteria and 146 DNA samples were successfully extracted. IDH1/2
      status was successfully obtained in 91% of cases. All but one positive IDH1 R132H
      IHC cases were concordantly detected by PCR and 3 were not detected by
      sequencing. Among the IHC-negative cases (n = 72), PCR detected 12 additional
      rare mutations (10 IDH1, 2 IDH2). All mutations detected by sequencing (n = 67)
      were concordantly detected by PCR and 5/66 sequencing-negative cases were PCR
      positive (overall concordance: 96%). Analysis of synthetic samples representative
      of the 11 rare IDH1/2 mutations detected by the assay produced 100% correct
      results. CONCLUSIONS: The new IDH1/2 PCR assay has a high technical success rate
      and is more sensitive than Sanger sequencing. Positive concordance was 98% with
      IHC for IDH1 R132H detection and 100% with sequencing. The PCR assay can reliably
      be performed on FFPE samples and has a faster turnaround time than current IDH
      mutation detection algorithms. The assay should facilitate implementation of a
      comprehensive IDH1/2 testing protocol in routine clinical practice.

PMID- 24889505
TI  - Efficacy and safety of percutaneous radiofrequency ablation versus surgical
      resection for small hepatocellular carcinoma: a meta-analysis of 23 studies.
AB  - PURPOSE: The aim of our meta-analysis was to compare the efficacy and safety of
      radiofrequency ablation (RFA) versus surgical resection for patients with small
      hepatocellular carcinoma (SHCC). METHODS: Randomized controlled trials (RCTs) or
      retrospective studies comparing the RFA with surgical resection for patients with
      SHCC published from 2004 to 2014 were selected from database of PubMed, EMBASE
      and Cochrane library. The outcomes including overall survival rate, recurrence
      free survival rate, recurrence rate and complications (mortality rate and
      morbidity rate) were abstracted. Individual and pooled odds ratio with 95%
      confidence interval of each outcome was analyzed. RESULTS: Three RCTs and twenty
      retrospective studies were included with a total of 15,482 patients. The 1-, 3-
      and 5-year overall survival rate and recurrence-free survival rate of surgical
      resection were significantly higher than RFA. The 2- and 3-year but not 1-year
      recurrence rate of RFA was significantly higher than surgical resection. The
      morbidity rate of complication in surgical resection group was higher than it in
      RFA group, but the mortality was not different between the two groups.
      CONCLUSION: Surgical resection led to a higher overall survival and recurrence
      free survival rate in treating SHCC. However, RFA led to a lower morbidity rate
      of complication than surgical resection.

PMID- 24889506
TI  - Exposure to perfluoroalkyl substances and sperm DNA global methylation in Arctic
      and European populations.
AB  - Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial
      processes and products, and have been detected globally in humans and wildlife.
      PFASs are suspected to interfere with endocrine signaling and to adversely affect
      human reproductive health. The aim of the present study was to investigate the
      associations between exposure to PFASs and sperm global methylation levels in a
      population of non-occupationally exposed fertile men. Measurements of PFASs in
      serum from 262 partners of pregnant women from Greenland, Poland and Ukraine,
      were also carried out by liquid chromatography tandem mass spectrometry.
      Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane
      sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of
      the blood samples. Two surrogate markers were used to assess DNA global
      methylation levels in semen samples from the same men: (a) average DNA
      methylation level in repetitive DNA sequences (Alu, LINE-1, Satalpha) quantified
      by PCR-pyrosequencing after bisulfite conversion; (b) flow cytometric
      immunodetection of 5-methyl-cytosines. After multivariate linear regression
      analysis, no major consistent associations between PFASs exposure and sperm DNA
      global methylation endpoints could be detected. However, since weak but
      statistically significant associations of different PFASs with DNA hypo- and
      hyper-methylation were found in some of the studied populations, effects of PFASs
      on sperm epigenetic processes cannot be completely excluded, and this issue
      warrants further investigation.

PMID- 24889508
TI  - Functional domains of the PETAL LOSS protein, a trihelix transcription factor
      that represses regional growth in Arabidopsis thaliana.
AB  - PETAL LOSS (PTL) is a trihelix transcription factor that represses growth,
      especially between sepal primordia. As one of 30 trihelix proteins in
      Arabidopsis, it falls in the GT2 clade with duplicated trihelix DNA-binding
      domains and a long alpha-helical central domain. PTL orthologs occur in all
      angiosperm genomes examined except grasses, and sequence comparisons reveal that
      there are two further short conserved domains at each end. GT2 itself carries two
      nuclear localization sequences, but PTL has an additional nuclear localization
      sequence (NLS). We show that PTL can act as a transcriptional activator in yeast
      and in planta, with the latter tested by two different functional assays.
      Specific deletions revealed that the activation region is C-terminal. Site
      directed mutagenesis of the DNA-binding domains has shown that a conserved
      tryptophan and two downstream acidic amino acids in the second trihelix,
      predicted to promote folding, are each required for PTL function. Also, three
      basic residues in the third helix, near the DNA interaction sites, support its
      function. PTL was found to dimerize in yeast. This was confirmed and extended by
      jointly expressing differentially tagged forms of PTL in a transient expression
      system in Nicotiana benthamiana leaves. Cytoplasmic PTL (with mutant NLS
      sequences) was carried into the nucleus upon binding with nuclear-localized PTL,
      providing each partner carried intact central domains. As this 90-amino acid
      domain is conserved in most trihelix family members, it seems likely that they
      all function in dimeric form.

PMID- 24889509
TI  - In memoriam: William A. Edelstein, 1944-2014.

PMID- 24889507
TI  - Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in
      tuberous sclerosis complex.
AB  - Mutations in the Tsc1 or Tsc2 genes cause tuberous sclerosis complex (TSC). Tsc1
      and Tsc2 proteins form a complex that inhibits mammalian target of rapamycin
      complex 1 (mTORC1) signalling through Rheb-GTPase. We found that Tsc2(+/-)
      neurons showed impaired spine synapse formation, which was resistant to an mTORC1
      inhibitor. Knockdown of mTOR also failed to restore these abnormalities,
      suggesting mTORC may not participate in impaired spinogenesis in Tsc2(+/-)
      neurons. To address whether Rheb activation impairs spine synapse formation, we
      expressed active and inactive forms of Rheb in WT and Tsc2(+/-) neurons,
      respectively. Expression of active Rheb abolished dendritic spine formation in WT
      neurons, whereas inactive Rheb restored spine synapse formation in Tsc2(+/-)
      neurons. Moreover, inactivation of Rheb with farnesyl transferase inhibitors
      recovered spine synapse morphogenesis in Tsc2(+/-) neurons. In conclusion,
      dendritic spine abnormalities in TSC neurons may be caused through activation of
      Rheb, but not through of mTORC1. 

PMID- 24889510
TI  - MR diffusion is sensitive to mechanical loading in human intervertebral disks ex
      vivo.
AB  - PURPOSE: To use T2 and diffusion MR to determine the change in the mechanical
      function of human disks with increased degenerative state. MATERIALS AND METHODS:
      Spatial changes in T2 and diffusion were quantified in five cadaveric human
      lumbar disks under compressive loads. Regression models were used to investigate
      the relationship between the change in MR parameters and the disk's dynamic and
      viscoelastic properties. RESULTS: Compressive loading caused a significant
      reduction in the disk's mean diffusivity ([11.3 versus 9.7].10(-4) .mm(2) /s, P <
      0.001) but little change in T2 (P < 0.05). Diffusivity and T2 were correlated
      with the disk's dynamic (P < 0.01 and P < 0.05) and long-term viscoelastic (P <
      0.05 and P < 0.05) stiffness. Diffusivity but not T2, was correlated with its
      viscoelastic dampening (r(2) = 0.45, P < 0.01) and instantaneous stiffness (r(2)
      = 0.44, P < 0.05). Nucleus diffusivity was significantly higher than the
      annulus's (-21% to -4%, P < 0.01). MR-estimated hydration was correlated with the
      instantaneous viscoelastic stiffness of the nucleus (r(2) = 0.35, P < 0.05) and
      the dynamic (r(2) = 0.44, P < 0.05) and long-term viscoelastic (r(2) = 0.42, P <
      0.05) stiffness in the annulus. T2 correlated with diffusivity at low load (r(2)
      = 0.66, P < 0.05), but not at high load. CONCLUSION: The strong correlations
      between diffusivity and the rheological assessments of disk mechanics suggest
      that MR might permit quantitative assessment of disk functional status and
      structural integrity.

PMID- 24889512
TI  - Do males matter? Testing the effects of male genetic background on female meiotic
      crossover rates in Drosophila melanogaster.
AB  - Meiotic recombination is a critical genetic process as well as a pivotal
      evolutionary force. Rates of crossing over are highly variable within and between
      species, due to both genetic and environmental factors. Early studies in
      Drosophila implicated female genetic background as a major determinant of
      crossover rate and recent work has highlighted male genetic background as a
      possible mediator as well. Our study employed classical genetics to address how
      female and male genetic backgrounds individually and jointly affect crossover
      rates. We measured rates of crossing over in a 33 cM region of the Drosophila
      melanogaster X chromosome using a two-step crossing scheme exploiting visible
      markers. In total, we measured crossover rates of 10 inbred lines in a full
      diallel cross. Our experimental design facilitates measuring the contributions of
      female genetic background, male genetic background, and female by male genetic
      background interaction effects on rates of crossing over in females. Our results
      indicate that although female genetic background significantly affects female
      meiotic crossover rates in Drosophila, male genetic background and the
      interaction of female and male genetic backgrounds have no significant effect.
      These findings thus suggest that male-mediated effects are unlikely to contribute
      greatly to variation in recombination rates in natural populations of Drosophila.

PMID- 24889511
TI  - Genomic aberrations deletion 11q and deletion 17p independently predict for worse
      progression-free and overall survival after allogeneic hematopoietic cell
      transplantation for chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia remains incurable despite availability of potent
      chemoimmunotherapy regimens. Allogeneic hematopoietic cell transplantation (HCT)
      is the only modality that offers the possibility of cure. To identify predictors
      of progression-free and overall survival, we evaluated outcomes of 43 consecutive
      patients who received an allograft for advanced CLL. The majority received a
      reduced intensity conditioning regimen (n=37). Donors were HLA matched-related
      (n=18), matched-unrelated (n=15), mismatched-unrelated (n=7), or umbilical cord
      blood (n=3). The median progression-free (PFS) and overall survival (OS) were
      31.4 months and 46.4 months respectively. Twenty (46.5%) patients were alive and
      in complete remission at a median follow-up of 31.4 months. NRM was higher than
      previously published series for CLL, likely due to a high burden of comorbidity
      (22 patients with HCT-CI >= 2) and a high proportion receiving HLA mismatched
      unrelated donor or umbilical cord blood cells. Presence of del (11q), del(17p),
      or progressive disease at HCT are independent predictors of worse PFS and OS. New
      strategies are needed to improve survival outcomes in CLL associated with poor
      risk cytogenetics.

PMID- 24889513
TI  - Epigenetic reprogramming of human lung cancer cells with the extract of bovine
      parthenogenetic oocytes.
AB  - The tumour suppressor gene silencing and proto-oncogene activation caused by
      epigenetic alterations plays an important role in the initiation and progression
      of cancer. Re-establishing the balance between the expression of tumour
      suppressor genes and proto-oncogenes by epigenetic modulation is a promising
      strategy for cancer treatment. In this study, we investigated whether cancer
      cells can be epigenetically reprogrammed by oocyte extract. H460 human lung
      cancer cells were reversibly permeabilized and incubated with the extract of
      bovine parthenogenetic oocytes. Bisulphite sequencing showed that bovine
      parthenogenetic oocyte extract induced significant demethylation at the promoters
      of the tumour suppressor genes RUNX3 and CDH1, but not at the promoter of the
      oncogenic pluripotency gene SOX2. Chromatin immunoprecipitation showed that the
      histone modifications at RUNX3 and CDH1 promoters were modulated towards a
      transcriptionally activating state, while those at SOX2 promoter towards a
      transcriptionally repressive state. Correspondingly, bovine parthenogenetic
      oocyte extract reversed the epigenetic silencing of RUNX3 and CDH1, and repressed
      the expression of SOX2. At the functional level, proliferation, anchorage
      independent growth, migration and invasion of H460 cells was strongly inhibited.
      These results indicate that bovine parthenogenetic oocyte extract changes the
      expression patterns of tumour suppressor and oncogenic genes in cancer cells by
      remodelling the epigenetic modifications at their promoters. Bovine
      parthenogenetic oocyte extract may provide a useful tool for epigenetically
      reprogramming cancer cells and for dissecting the epigenetic mechanisms involved
      in tumorigenesis. 

PMID- 24889515
TI  - Two-photon probes for metal ions based on phenylaza[18]crown-6 ethers and 1,2,3
      triazoles as pi-linkers.

PMID- 24889514
TI  - Providing specialty consultant expertise to primary care: an expanding spectrum
      of modalities.
AB  - In most models of health care delivery, the bulk of services are provided in
      primary care and there is frequent request for the input of specialty
      consultants. A critical issue for current and future health care systems is the
      effective and efficient delivery of specialist expertise for clinicians and
      patients. Input on a patient's care from specialty consultants usually requires a
      face-to-face visit between the patient and the consultant. New and complementary
      models of knowledge sharing have emerged. We describe a framework assessment of a
      spectrum of knowledge-sharing methods in the context of a patient-centered
      medical home. This framework is based on our experience in the Veterans Health
      Administration and a purposive review of the literature. These newer modes of
      specialty consultation include electronic consultation, secure text messaging,
      telemedicine of various types, and population preemptive consults. In addition to
      describing these modes of consultation, our framework points to several important
      areas in which further research is needed to optimize effectiveness. 

PMID- 24889516
TI  - Blood glucose is associated with chronic kidney disease in subjects with impaired
      glucose tolerance, but not in those with impaired fasting glucose.

PMID- 24889517
TI  - 'Click' chemistry synthesis and capillary electrophoresis study of 1,4-linked
      1,2,3-triazole AZT-systemin conjugate.
AB  - The Cu(I) catalyzed Huisgen 1,3-dipolar azide-alkyne cycloaddition (CuAAC) was
      applied for a nucleoside-peptide bioconjugation. Systemin (Sys), an 18-aa plant
      signaling peptide naturally produced in response to wounding or pathogen attack,
      was chemically synthesized as its N-propynoic acid functionalized analog (Prp
      Sys) using the SPPS. Next, CuAAC was applied to conjugate Prp-Sys with 3'-azido
      2',3'-dideoxythymidine (AZT), a model cargo molecule. 1,4-Linked 1,2,3-triazole
      AZT-Sys conjugate was designed to characterize the spreading properties and
      ability to translocate of cargo molecules of systemin. CuAAC allowed the
      synthesis of the conjugate in a chemoselective and regioselective manner, with
      high purity and yield. The presence of Cu(I) ions generated in situ drove the
      CuAAC reaction to completion within a few minutes without any by-products. Under
      typical separation conditions of phosphate 'buffer' at low pH and uncoated fused
      bare-silica capillary, an increasing peak intensity assigned to triazole-linked
      AZT-Sys conjugate was observed using capillary electrophoresis (CE) during CuAAC.
      CE analysis showed that systemin peptides are stable in tomato leaf extract for
      up to a few hours. CE-ESI-MS revealed that the native Sys and its conjugate with
      AZT are translocated through the tomato stem and can be directly detected in stem
      exudates. The results show potential application of systemin as a transporter of
      low molecular weight cargo molecules in tomato plant and of CE method to
      characterize a behavior of plant peptides and its analogs.

PMID- 24889518
TI  - Ghrelin accelerates in vitro maturation of bovine oocytes.
AB  - Ghrelin, apart from its metabolic role, is nowadays considered as a basic
      regulator of reproductive functions of mammals, acting at central and gonadal
      levels. Here, we investigated for possible direct actions of ghrelin on in vitro
      maturation of bovine oocytes and for its effects on blastocyst yield and quality.
      In experiment 1, cumulus oocyte complexes (COCs) were matured in the presence of
      four different concentrations of ghrelin (0, 200, 800 and 2000 pg/ml). In vitro
      fertilization and embryo culture were carried out in the absence of ghrelin, and
      blastocyst formation rates were examined on days 7, 8 and 9. In experiment 2,
      only the 800 pg/ml dose of ghrelin was used. Four groups of COCs were matured for
      18 or 24 h (C18, Ghr18, C24 and Ghr24), and subsequently, they were examined for
      oocyte nuclear maturation and cumulus layer expansion; blastocysts were produced
      as in experiment 1. The relative mRNA abundance of various genes related to
      metabolism, oxidation, developmental competence and apoptosis was examined in
      snap-frozen cumulus cells, oocytes and day-7 blastocysts. In experiment 1,
      ghrelin significantly suppressed blastocyst formation rates. In experiment 2,
      more ghrelin-treated oocytes matured for 18 h reached MII compared with controls,
      while no difference was observed when maturation lasted for 24 h. At 18 and 24 h,
      the cumulus layer was more expanded in ghrelin-treated COCs than in the controls.
      The blastocyst formation rate was higher in Ghr18 (27.7 +/- 2.4%) compared with
      Ghr24 (17.5 +/- 2.4%). Differences were detected in various genes' expression,
      indicating that in the presence of ghrelin, incubation of COCs for 24 h caused
      over-maturation (induced ageing) of oocytes, but formed blastocysts had a higher
      hatching rate compared with the controls. We infer that ghrelin exerts a specific
      and direct role on the oocyte, accelerating its maturational process.

PMID- 24889519
TI  - The past, present and future of secondary metabolite research in the
      Dothideomycetes.
AB  - The Dothideomycetes represents a large and diverse array of fungi in which
      prominent plant pathogens are over-represented. Species within the Cochliobolus,
      Alternaria, Pyrenophora and Mycosphaerella (amongst others) all cause diseases
      that threaten food security in many parts of the world. Significant progress has
      been made over the past decade in understanding how some of these pathogens cause
      disease at a molecular level. It is reasonable to suggest that much of this
      progress can be attributed to the increased availability of genome sequences.
      However, together with revealing mechanisms of pathogenicity, these genome
      sequences have also highlighted the capacity of the Dothideomycetes to produce an
      extensive array of secondary metabolites, far greater than originally thought.
      Indeed, it is now clear that we appear to have only scratched the surface to date
      in terms of the identification of secondary metabolites produced by these fungi.
      In the first half of this review, we examine the current status of secondary
      metabolite research in the Dothideomycetes and highlight the diversity of the
      molecules discovered thus far, in terms of both structure and biological
      activity. In the second part of this review, we survey the emerging techniques
      and technologies that will be required to shed light on the vast array of
      secondary metabolite potential that is encoded within these genomes. Experimental
      design, analytical chemistry and synthetic biology are all discussed in the
      context of how they will contribute to this field. 

PMID- 24889520
TI  - Device therapy: CRT effective in elderly patients with heart failure.

PMID- 24889522
TI  - Interventional cardiology: Transformation to transradial--safe and effective.

PMID- 24889523
TI  - Study on the pharmacokinetics and metabolism of costunolide and dehydrocostus
      lactone in rats by HPLC-UV and UPLC-Q-TOF/MS.
AB  - A method based on high-performance liquid chromatography coupled with ultraviolet
      detection was developed for studying the pharmacokinetics of costunolide (Cos)
      and dehydrocostus lactone (Dehy) in rats after intravenous (i.v.) administration.
      Following i.v. administration, the maximum plasma concentrations of Cos and Dehy
      were observed to be 12.29 +/- 1.47 and 5.79 +/- 0.13 ug/mL, respectively. The
      bioavailability of Cos was larger than that of Dehy; however, the clearance and
      the volume of distribution of Dehy were much larger than those of Cos. An
      ultraperformance liquid chromatography/quadrupole time-of-flight mass
      spectrometry system with automated MS(E) (E represents collision energy) data
      analysis software (MetaboLynx(TM)) was used to analyze and identify the
      metabolites of Cos and Dehy in vivo. Four metabolites of Cos and six metabolites
      of Dehy were discovered from the plasma, urine and feces of rats. The main
      metabolic pathway of Cos was phase II biotransformation, but the main metabolic
      pathways of Dehy was phase I biotransformation. Two sequential desaturations and
      N-acetylcysteine conjugation were the common metabolic pathways of Cos and Dehy
      in rats. This information may be useful for the further development of the two
      drug candidates.

PMID- 24889524
TI  - Allenamides as orthogonal handles for selective modification of cysteine in
      peptides and proteins.
AB  - In this study, a remarkably simple and direct strategy has been successfully
      developed to selectively label target cysteine residues in fully unprotected
      peptides and proteins. The strategy is based on the reaction between allenamides
      and the cysteine thiol, and proceeds swiftly in aqueous medium with excellent
      selectivity and quantitative conversion, thus forming a stable and irreversible
      conjugate. The combined simplicity and mildness of the process project allenamide
      as robust and versatile handles to target cysteines and has potential use in
      biological systems. Additionally, fluorescent-labeling studies demonstrated that
      the installation of a C-terminal allenamide moiety onto various molecules of
      interest may supply a new methodology towards the site-specific labeling of
      cysteine-containing proteins. Such a new labeling strategy may thus open a window
      for its application in the field of life sciences. 

PMID- 24889521
TI  - The vortex--an early predictor of cardiovascular outcome?
AB  - Blood motion in the heart features vortices that accompany the redirection of jet
      flows towards the outlet tracks. Vortices have a crucial role in fluid dynamics.
      The stability of cardiac vorticity is vital to the dynamic balance between
      rotating blood and myocardial tissue and to the development of cardiac
      dysfunction. Moreover, vortex dynamics immediately reflect physiological changes
      to the surrounding system, and can provide early indications of long-term
      outcome. However, the pathophysiological relevance of cardiac fluid dynamics is
      still unknown. We postulate that maladaptive intracardiac vortex dynamics might
      modulate the progressive remodelling of the left ventricle towards heart failure.
      The evaluation of blood flow presents a new paradigm in cardiac function
      analysis, with the potential for sensitive risk identification of cardiac
      abnormalities. Description of cardiac flow patterns after surgery or device
      therapy provides an intrinsic qualitative evaluation of therapeutic procedures,
      and could enable early risk stratification of patients vulnerable to adverse
      cardiac remodelling.

PMID- 24889526
TI  - Therapeutic mammaplasty.
AB  - Therapeutic mammaplasty is a term for the oncoplastic application of breast
      reduction and mastopexy techniques to treat selected breast tumours by breast
      conserving surgery (BCS). It has the potential to increase the indications for
      BCS as well as achieve more acceptable aesthetic results from it in suitable
      women. Now an established technique in the range of oncoplastic options for women
      with breast cancer, it finds common application and is associated with good
      oncological and quality of life outcomes.

PMID- 24889525
TI  - Efficacy of natural diosgenin on cardiovascular risk, insulin secretion, and beta
      cells in streptozotocin (STZ)-induced diabetic rats.
AB  - Costus igneus, has been prescribed for the treatment of diabetic mellitus in
      India for several years. The aim of this study is to investigate the effects of
      plant derived diosgenin on cardiovascular risk, insulin secretion, and pancreatic
      composition through electron microscopical studies of normal and diabetic rats.
      Diosgenin at a dose of 5 or 10mg/kg per body weight (bw) was orally administered
      as a single dose per day to diabetic induced rats for a period of 30 days. The
      effect of diosgenin on blood glucose, HbA1c, PT, APTT, Oxy-LDL, serum lipid
      profile, electron microscopical studies of pancreas, antioxidant enzymes (in
      liver, kidney, pancreas) and hepatoprotective enzymes in plasma and liver were
      measured in normal and diabetic rats. The results showed that fasting blood
      glucose, PT, APTT, Oxy-LDL, TC, TG, LDL, ALT, AST, ALP, glucose-6-phosphatase,
      fructose-1,6-bisphosphatase and LPO levels were significantly (p<0.05) increased,
      whereas HDL, SOD, CAT, GSH and the glycolytic enzyme glucokinase levels were
      significantly (p<0.05) decreased in the diabetes induced rats and these levels
      were significantly (p<0.05) reversed back to normal in diabetes induced rats
      after 30 days of treatment with diosgenin. Electron microscopical studies of the
      pancreas revealed that the number of beta cells and insulin granules were
      increased in streptozotocin (STZ) induced diabetic rats after 30 days of
      treatment with diosgenin. In conclusion, the data obtained from the present study
      strongly indicate that diosgenin has potential effects on cardiovascular risk,
      insulin secretion and beta cell regeneration in STZ induced diabetic rats, these
      results could be useful for new drug development to fight diabetes and its
      related cardiovascular diseases. 

PMID- 24889527
TI  - Mediator subunit 16 functions in the regulation of iron uptake gene expression in
      Arabidopsis.
AB  - Iron is an essential nutrient for plant growth and development, and its
      absorption is tightly controlled. Under iron limitation, FIT dimerizes with the
      four Ib bHLH proteins and activates the expression of iron uptake genes. However,
      how the dimerized complex activates downstream genes remains unclear. Using
      forward genetics, a low-iron-sensitive mutant was screened. The corresponding
      gene (MED16) was isolated, and its biological functions in iron homeostasis were
      characterized using approaches such as gene expression, protein subcellular
      localization, protein-protein interaction and chromatin immunoprecipitation
      assay. Lesion of MED16 significantly reduced FRO2 and IRT1 expression in
      Arabidopsis roots. The MED16 mutants showed a low shoot iron concentration and
      severe leaf chlorosis under iron limitation, whereas it grew normally as wild
      type under iron sufficiency. Furthermore, we showed that MED16 interacted with
      FIT and improved the binding of the FIT/Ib bHLH complex to FRO2 and IRT1
      promoters under iron-deficient conditions. Additionally, we found that many iron
      deficient response genes, which are regulated by FIT, were also controlled by
      MED16. In conclusion, MED16 is involved in the iron deficiency response, and
      modulates the iron uptake gene expression under iron limitation. Our results
      increase the understanding of the molecular regulation mechanisms underlying iron
      uptake and homeostasis in plants. 

PMID- 24889529
TI  - Therapeutic cancer vaccines.
AB  - Therapeutic cancer vaccines have the potential of being integrated in the therapy
      of numerous cancer types and stages. The wide spectrum of vaccine platforms and
      vaccine targets is reviewed along with the potential for development of vaccines
      to target cancer cell "stemness," the epithelial-to-mesenchymal transition (EMT)
      phenotype, and drug-resistant populations. Preclinical and recent clinical
      studies are now revealing how vaccines can optimally be used with other immune
      based therapies such as checkpoint inhibitors, and so-called nonimmune-based
      therapeutics, radiation, hormonal therapy, and certain small molecule targeted
      therapies; it is now being revealed that many of these traditional therapies can
      lyse tumor cells in a manner as to further potentiate the host immune response,
      alter the phenotype of nonlysed tumor cells to render them more susceptible to T
      cell lysis, and/or shift the balance of effector:regulatory cells in a manner to
      enhance vaccine efficacy. The importance of the tumor microenvironment, the
      appropriate patient population, and clinical trial endpoints is also discussed in
      the context of optimizing patient benefit from vaccine-mediated therapy. 

PMID- 24889530
TI  - IKK/nuclear factor-kappaB and oncogenesis: roles in tumor-initiating cells and in
      the tumor microenvironment.
AB  - The IKK/nuclear factor-kappaB pathway (NF-kappaB) is critical in proper immune
      function, cell survival, apoptosis, cellular proliferation, synaptic plasticity,
      and even memory. While NF-kappaB is crucial for both innate and adaptive
      immunity, defective regulation of this master transcriptional regulator is seen
      in a variety of diseases including autoimmune disease, neurodegenerative disease,
      and, important to this review, cancer. While NF-kappaB functions in cancer to
      promote a number of critical oncogenic functions, here we discuss the importance
      of the NF-kappaB signaling pathway in contributing to cancer through promotion of
      the tumor microenvironment and through maintenance/expansion of tumor-initiating
      cells, processes that appear to be functionally interrelated. 

PMID- 24889531
TI  - The Rb-E2F transcriptional regulatory pathway in tumor angiogenesis and
      metastasis.
AB  - The retinoblastoma tumor suppressor protein Rb plays a major role in regulating
      G1/S transition and is a critical regulator of cell proliferation. Rb protein
      exerts its growth regulatory properties mainly by physically interacting with the
      transcriptionally active members of the E2F transcription factor family,
      especially E2Fs 1, 2, and 3. Given its critical role in regulating cell
      proliferation, it is not surprising that Rb is inactivated in almost all tumors,
      either through the mutation of Rb gene itself or through the mutations of its
      upstream regulators including K-Ras and INK4. Recent studies have revealed a
      significant role for Rb and its downstream effectors, especially E2Fs, in
      regulating various aspects of tumor progression, angiogenesis, and metastasis.
      Thus, components of the Rb-E2F pathway have been shown to regulate the expression
      of genes involved in angiogenesis, including VEGF and VEGFR, genes involved in
      epithelial-mesenchymal transition including E-cadherin and ZEB proteins, and
      genes involved in invasion and migration like matrix metalloproteinases. Rb has
      also been shown to play a major role in the functioning of normal and cancer stem
      cells; further, Rb and E2F appear to play a regulatory role in the energy
      metabolism of cancer cells. These findings raise the possibility that mutational
      events that initiate tumorigenesis by inducing uncontrolled cell proliferation
      might also contribute to the progression and metastasis of cancers through the
      mediation of the Rb-E2F transcriptional regulatory pathway. This review
      highlights these recent studies on tumor promoting functions of the Rb-E2F
      pathway. 

PMID- 24889533
TI  - Diffuse intrinsic pontine gliomas: treatments and controversies.
AB  - Diffuse intrinsic pontine gliomas (DIPGs) are a fairly common pediatric brain
      tumor, and children with these tumors have a dismal prognosis. They generally are
      diagnosed within the first decade of life, and due to their location within the
      pons, these tumors are not surgically resectable. The median survival for
      children with DIPGs is less than 1 year, in spite of decades of clinical trial
      development of unique approaches to radiation therapy and chemotherapy. Novel
      therapies are under investigation for these deadly tumors. As clinicians and
      researchers make a concerted effort to obtain tumor tissue, the molecular signals
      of these tumors are being investigated in an attempt to uncover targetable
      therapies for DIPGs. In addition, direct application of chemotherapies into the
      tumor (convection-enhanced delivery) is being investigated as a novel delivery
      system for treatment of DIPGs. Overall, DIPGs require creative thinking and a
      disciplined approach for development of a therapy that can improve the prognosis
      for these unfortunate children. 

PMID- 24889534
TI  - In vivo modeling of malignant glioma: the road to effective therapy.
AB  - Despite an increased emphasis on developing new therapies for malignant gliomas,
      they remain among the most intractable tumors faced today as they demonstrate a
      remarkable ability to evade current treatment strategies. Numerous candidate
      treatments fail at late stages, often after showing promising preclinical
      results. This disconnect highlights the continued need for improved animal models
      of glioma, which can be used to both screen potential targets and authentically
      recapitulate the human condition. This review examines recent developments in the
      animal modeling of glioma, from more established rat models to intriguing new
      systems using Drosophila and zebrafish that set the stage for higher throughput
      studies of potentially useful targets. It also addresses the versatility of mouse
      modeling using newly developed techniques recreating human protocols and
      sophisticated genetically engineered approaches that aim to characterize the
      biology of gliomagenesis. The use of these and future models will elucidate both
      new targets and effective combination therapies that will impact on disease
      management. 

PMID- 24889536
TI  - Life is three dimensional-as in vitro cancer cultures should be.
AB  - For many decades, fundamental cancer research has relied on two-dimensional in
      vitro cell culture models. However, these provide a poor representation of the
      complex three-dimensional (3D) architecture of living tissues. The more recent 3D
      culture systems, which range from ridged scaffolds to semiliquid gels, resemble
      their natural counterparts more closely. The arrangement of the cells in 3D
      systems allows better cell-cell interaction and facilitates extracellular matrix
      secretion, with concomitant effects on gene and protein expression and cellular
      behavior. Many studies have reported differences between 3D and 2D systems as
      regards responses to therapeutic agents and pivotal cellular processes such as
      cell differentiation, morphology, and signaling pathways, demonstrating the
      importance of 3D culturing for various cancer cell lines. 

PMID- 24889537
TI  - An electro-coalescence chip for effective emulsion breaking in droplet
      microfluidics.
AB  - Droplet-based microfluidics is increasingly used for biological applications,
      where the recovery of cells or particles after an experiment or assay is
      desirable. Here, we present an electro-demulsification chip which circumvents the
      use of harsh chemicals and multiple washing/centrifugation steps and offers a
      mild way for extracting cells and polymer particles into an aqueous phase from
      microfluidic water-in-oil emulsions. 

PMID- 24889538
TI  - Inkjet printing of conductive inks with high lateral resolution on omniphobic
      "R(F) paper" for paper-based electronics and MEMS.
AB  - The use of omniphobic "fluoroalkylated paper" as a substrate for inkjet printing
      of aqueous inks that are the precursors of electrically conductive patterns is
      described. By controlling the surface chemistry of the paper, it is possible to
      print high resolution, conductive patterns that remain conductive after folding
      and exposure to common solvents. 

PMID- 24889528
TI  - Glial progenitors as targets for transformation in glioma.
AB  - Glioma is the most common primary malignant brain tumor and arises throughout the
      central nervous system. Recent focus on stem-like glioma cells has implicated
      neural stem cells (NSCs), a minor precursor population restricted to germinal
      zones, as a potential source of gliomas. In this review, we focus on the
      relationship between oligodendrocyte progenitor cells (OPCs), the largest
      population of cycling glial progenitors in the postnatal brain, and
      gliomagenesis. OPCs can give rise to gliomas, with signaling pathways associated
      with NSCs also playing key roles during OPC lineage development. Gliomas can also
      undergo a switch from progenitor- to stem-like phenotype after therapy,
      consistent with an OPC-origin even for stem-like gliomas. Future in-depth studies
      of OPC biology may shed light on the etiology of OPC-derived gliomas and reveal
      new therapeutic avenues. 

PMID- 24889532
TI  - ATP-dependent chromatin remodeling complexes as novel targets for cancer therapy.
AB  - The progression to advanced stage cancer requires changes in many characteristics
      of a cell. These changes are usually initiated through spontaneous mutation. As a
      result of these mutations, gene expression is almost invariably altered allowing
      the cell to acquire tumor-promoting characteristics. These abnormal gene
      expression patterns are in part enabled by the posttranslational modification and
      remodeling of nucleosomes in chromatin. These chromatin modifications are
      established by a functionally diverse family of enzymes including histone and DNA
      modifying complexes, histone deposition pathways, and chromatin remodeling
      complexes. Because the modifications these enzymes deposit are essential for
      maintaining tumor-promoting gene expression, they have recently attracted much
      interest as novel therapeutic targets. One class of enzyme that has not generated
      much interest is the chromatin remodeling complexes. In this review, we will
      present evidence from the literature that these enzymes have both causal and
      enabling roles in the transition to advanced stage cancers; as such, they should
      be seriously considered as high-value therapeutic targets. Previously published
      strategies for discovering small molecule regulators to these complexes are
      described. We close with thoughts on future research, the field should perform to
      further develop this potentially novel class of therapeutic target. 

PMID- 24889539
TI  - Inhibition of platelet activation prevents the P-selectin and integrin-dependent
      accumulation of cancer cell microparticles and reduces tumor growth and
      metastasis in vivo.
AB  - Venous thromboembolism constitutes one of the main causes of death during the
      progression of a cancer. We previously demonstrated that tissue factor (TF)
      bearing cancer cell-derived microparticles accumulate at the site of injury in
      mice developing a pancreatic cancer. The presence of these microparticles at the
      site of thrombosis correlates with the size of the platelet-rich thrombus. The
      objective of this study was to determine the involvement of TF expressed by
      cancer cell-derived microparticles on thrombosis associated with cancer. We
      observed that pancreatic cancer cell derived microparticles expressed TF, its
      inhibitor tissue factor pathway inhibitor (TFPI) as well as the integrins
      alphavbeta1 and alphavbeta3. In mice bearing a tumor under-expressing TF, a
      significant decrease in circulating TF activity associated with an increase
      bleeding time and a 100-fold diminished fibrin generation and platelet
      accumulation at the site of injury were observed. This was mainly due to the
      interaction of circulating cancer cell-derived microparticles expressing TFPI
      with activated platelets and fibrinogen. In an ectopic model of cancer, treatment
      of mice with Clopidogrel, an anti-platelet drug, decreased the size of the tumors
      and restored hemostasis by preventing the accumulation of cancer cell-derived
      microparticles at the site of thrombosis. In a syngeneic orthotopic model of
      pancreatic cancer Clopidogrel also significantly inhibited the development of
      metastases. Together, these results indicate that an anti-platelet strategy may
      efficiently treat thrombosis associated with cancer and reduce the progression of
      pancreatic cancer in mice. 

PMID- 24889535
TI  - Genetically engineered mice as experimental tools to dissect the critical events
      in breast cancer.
AB  - Elucidating the mechanism of pathogenesis of breast cancer has greatly benefited
      from breakthrough advances in both genetically engineered mouse (GEM) models and
      xenograft transplantation technologies. The vast array of breast cancer mouse
      models currently available is testimony to the complexity of mammary
      tumorigenesis and attempts by investigators to accurately portray the
      heterogeneity and intricacies of this disease. Distinct molecular changes that
      drive various aspects of tumorigenesis, such as alterations in tumor cell
      proliferation and apoptosis, invasion and metastasis, angiogenesis, and drug
      resistance have been evaluated using the currently available GEM breast cancer
      models. GEM breast cancer models are also being exploited to evaluate and
      validate the efficacy of novel therapeutics, vaccines, and imaging modalities for
      potential use in the clinic. This review provides a synopsis of the various GEM
      models that are expanding our knowledge of the nuances of breast cancer
      development and progression and can be instrumental in the development of novel
      prevention and therapeutic approaches for this disease. 

PMID- 24889540
TI  - Outcome-adaptive randomization for a delayed outcome with a short-term predictor:
      imputation-based designs.
AB  - Delay in the outcome variable is challenging for outcome-adaptive randomization,
      as it creates a lag between the number of subjects accrued and the information
      known at the time of the analysis. Motivated by a real-life pediatric ulcerative
      colitis trial, we consider a case where a short-term predictor is available for
      the delayed outcome. When a short-term predictor is not considered, studies have
      shown that the asymptotic properties of many outcome-adaptive randomization
      designs are little affected unless the lag is unreasonably large relative to the
      accrual process. These theoretical results assumed independent identical delays,
      however, whereas delays in the presence of a short-term predictor may only be
      conditionally homogeneous. We consider delayed outcomes as missing and propose
      mitigating the delay effect by imputing them. We apply this approach to the
      doubly adaptive biased coin design (DBCD) for motivating pediatric ulcerative
      colitis trial. We provide theoretical results that if the delays, although non
      homogeneous, are reasonably short relative to the accrual process similarly as in
      the iid delay case, the lag is also asymptotically ignorable in the sense that a
      standard DBCD that utilizes only observed outcomes attains target allocation
      ratios in the limit. Empirical studies, however, indicate that imputation-based
      DBCDs performed more reliably in finite samples with smaller root mean square
      errors. The empirical studies assumed a common clinical setting where a delayed
      outcome is positively correlated with a short-term predictor similarly between
      treatment arm groups. We varied the strength of the correlation and considered
      fast and slow accrual settings.

PMID- 24889543
TI  - [Self-assessment of patterns of antibiotic use in a university hospital].
AB  - INTRODUCTION: A questionnaire was used to determine the knowledge, attitudes and
      practices of antibiotic prescribing among doctors at a university hospital.
      METHODS: An anonymous questionnaire was directly distributed by a staff member of
      the Infectious Diseases Department. RESULTS: A total of 316 questionnaires were
      distributed with 100% response rate; antibiotic dose, route of administration,
      and treatment duration were always adjusted according to site of infection and
      underlying conditions in 65, 68 and 45%, respectively. Antibiotic de-escalation
      was recognized as usual practice in 20%; 31 and 10% considered potential
      microbiological resistances and economical-cost when taking prescription
      decisions, respectively; 16% admitted often prescribing antibiotics with no
      clinical indication. There were no major significant differences between staff
      and training physicians, or between surgical or medical specialists. CONCLUSIONS:
      The self-perception of physicians and residents in our hospital is that they make
      improper use of antimicrobials.

PMID- 24889541
TI  - Adherence to an antibiotic stewardship bundle targeting Staphylococcus aureus
      blood stream infections at a 200-bed community hospital.
AB  - PURPOSE: Bacteremia with Staphylococcus aureus (SAB) is a serious clinical
      condition and is associated with a high mortality, ranging from 20 to 40 %.
      Different trials from tertiary referral hospitals demonstrate that infectious
      disease consultation and adherence to standard of care indicators reduce the high
      mortality. Data from <250-bed general hospitals are lacking in this context.
      METHODS: Patient cases at a community 200-bed general hospital with documented
      SAB were retrospectively analyzed from January 2010 to March 2013 regarding
      defined standard of care indicators. In April 2013, an antibiotic stewardship
      bundle approach was implemented targeting SAB. Follow-up was available until
      December 2013. Adherence to the different components of the bundle was analyzed.
      RESULTS: There were 64 cases of SAB reported. After exclusion of five cases, 39
      cases were included in the pre-intervention period and 20 patients in the post
      intervention period. Mean average bundle adherence increased from a baseline
      score of 0.8-3.7 (p < 0.001) in the post-intervention period, whereas in-hospital
      mortality decreased significantly (44 vs. 10 %, p < 0.001) despite or even
      because the absolute number of detected cases of SAB increased substantially
      after the intervention was initiated. CONCLUSION: Although we were unable to
      identify whether the bundle, one of its components, or procedural improvements
      are responsible for the success of the intervention, our study indicates that the
      applied approach is feasible and is accompanied by a significant reduction of in
      hospital mortality in the secondary care setting. The intervention may serve as a
      model for other hospitals with similar structures and baseline situations.

PMID- 24889544
TI  - Ichthyosis prematurity syndrome: a case report and review of known mutations.
AB  - Ichthyosis prematurity syndrome (IPS; Mendelian Inheritance in Man 608649) is
      classified as a syndromic autosomal recessive ichthyosis. Here we describe two
      siblings with IPS and report a recurrent homozygous mutation (c.1430T>A) that is
      predicted to lead to a p.Val477Asp substitution in fatty acid transport protein
      4. This mutation has arisen for the second time in an entirely distinct
      population from the Scandinavian population where it was first described. 

PMID- 24889545
TI  - Towards a zero-waste oxidative coupling of nonactivated aromatics by supported
      gold nanoparticles.
AB  - We show that gold nanoparticles are able to perform the direct oxidative coupling
      of nonactivated aromatics with O2 as the only co-reagent. In this reaction, the
      aromatic acts both as reactant and solvent. Biphenyl, for example, can be
      obtained from benzene with high selectivity and a turnover number (TON) of 230
      per pass. Similarly, several substituted biaryls can be prepared. Pd performs
      only one TON and even when a second catalytic functionality is introduced,
      together with strong acidic conditions, TON is always lower than 100. Other
      catalysts require iodine for performing the reaction, leading to 2 kg of waste
      for 1 kg of biphenyl formed, whereas no waste is created by the oxidative
      coupling with gold nanoparticles.

PMID- 24889547
TI  - Ultrasound assisted production of a fibrinolytic enzyme in a bioreactor.
AB  - The present work illustrates ultrasound assisted production of a fibrinolytic
      enzyme at 1L bioreactor scale from Bacillus sphaericus MTCC 3672. To alleviate
      the shortcomings of one factor at a time method of optimization, central
      composite rotatable design of response surface methodology was employed for
      optimization of ultrasound assisted production. Different process parameters such
      as irradiation time, duty cycle and power of ultrasound were varied in 3
      different levels in 11 experimental runs. For evaluating mass transfer
      enhancement effect of ultrasonication on production, control non sonicated
      fermentation was optimized by varying different agitation speed (300-500rpm) and
      aeration rate (8.33-33.33cc/s). Optimized ultrasonication protocol resulted in
      1.48-fold increase in fibrinolytic enzyme yield as compared to non sonicated
      fermentation, which comprised of ultrasound irradiation at 25kHz for 10min with
      40% duty cycle and 160W power on 12h of growth phase in 1L bioreactor operated at
      400rpm agitation speed and 16.66cc/s aeration rate. Declined glucose
      concentration from 0.1% w/v (non sonicated control run) to 0.05% w/v and breakage
      of cells cluster emphasized on increased substrate utilization potential and
      enhanced convection of ultrasound assisted fermentation in a bioreactor.
      Deliverables of current studies will provide significant insights for enhancement
      of productivity of various enzymes at a bioreactor level. 

PMID- 24889546
TI  - Transcutaneous application of CO2 enhances the antitumor effect of radiation
      therapy in human malignant fibrous histiocytoma.
AB  - Sarcomas are relatively resistant because of hypoxia. We previously demonstrated
      that the transcutaneous CO(2) therapy reduced hypoxic conditions in human
      malignant fibrous histiocytoma (MFH). Therefore, we hypothesized that
      transcutaneous CO(2) therapy could enhance the antitumor effect of radiation
      therapy in human MFH. Our purpose was to evaluate the effects of transcutaneous
      CO(2) therapy on the antitumor efficacy of X-ray irradiation using MFH. First, in
      an in vitro study, we assessed apoptotic activity and reactive oxygen species
      (ROS) production using flow cytometric and immunoblot analysis at 24 h after X
      ray irradiation under three different oxygen conditions (normoxic, reoxygenated
      and hypoxic). In addition, in the in vivo study, 24 male athymic BALB/c nude mice
      with MFH tumors that were inoculated in the dorsal subcutaneous area were
      randomized into four groups: control, CO(2), X-ray irradiation and combination
      (CO(2) and X-ray irradiation). Treatments were performed twice weekly for 2
      weeks, four times in total. Tumor volume was calculated. All tumors were excised
      and apoptotic activity, ROS production, related proteins and HIF-1alpha
      expression were assessed using flow cytometric and immunoblot analysis. The in
      vitro study revealed that X-ray irradiation induced increased apoptosis and ROS
      production in MFH cells under normoxic and reoxygenated conditions relative to
      hypoxic conditions (P<0.01). In the in vivo study, tumor volume in the
      combination group was reduced to 28, 42 and 47% of that in the control, CO(2),
      and X-ray groups, respectively (P<0.05). Apoptotic activity and ROS production in
      the combination group were strongly increased with decreasing HIF-1alpha
      expression relative to the control, CO(2) and X-ray groups. The transcutaneous
      CO(2) system enhanced the antitumor action of X-ray irradiation and could be a
      novel therapeutic tool for overcoming radio-resistance in human malignancies.

PMID- 24889548
TI  - Modeling cavitation in a rapidly changing pressure field - application to a small
      ultrasonic horn.
AB  - Ultrasonic horn transducers are frequently used in applications of acoustic
      cavitation in liquids. It has been observed that if the horn tip is sufficiently
      small and driven at high amplitude, cavitation is very strong, and the tip can be
      covered entirely by the gas/vapor phase for longer time intervals. A peculiar
      dynamics of the attached cavity can emerge with expansion and collapse at a self
      generated frequency in the subharmonic range, i.e. below the acoustic driving
      frequency. The term "acoustic supercavitation" was proposed for this type of
      cavitation Znidarcic et al. (2014) [1]. We tested several established
      hydrodynamic cavitation models on this problem, but none of them was able to
      correctly predict the flow features. As a specific characteristic of such
      acoustic cavitation problems lies in the rapidly changing driving pressures, we
      present an improved approach to cavitation modeling, which does not neglect the
      second derivatives in the Rayleigh-Plesset equation. Comparison with measurements
      of acoustic supercavitation at an ultrasonic horn of 20kHz frequency revealed a
      good agreement in terms of cavity dynamics, cavity volume and emitted pressure
      pulsations. The newly developed cavitation model is particularly suited for
      simulation of cavitating flow in highly fluctuating driving pressure fields. 

PMID- 24889549
TI  - Ultrasonic disruption of fungal mycelia for efficient recovery of polysaccharide
      protein complexes from viscous fermentation broth of a medicinal fungus.
AB  - High-intensity ultrasound (US) was applied to facilitate the extraction of
      intracellular and extracellular polysaccharide-protein complexes (PSPs) from the
      viscous mycelial fermentation broth of a medicinal fungus Cordyceps sinensis Cs
      HK1. The US treatment caused the disruption of fungal mycelia, a dramatic
      reduction of the apparent broth viscosity, and the release of intracellular
      products into the liquid medium. The degree of mycelium disruption and the rate
      of intracellular product release were dependent on US power intensity, treatment
      period and biomass concentration of broth. The extraction or release kinetics of
      total water-soluble products and PSPs (yield Y versus time t) under the effect of
      US was fitted closely to the Elovich model Y=Yo+Y1 lnt and parabolic model
      Y=Yo+Y1t(1/2), respectively. Another interesting effect of the US treatment was a
      notable increase in the antioxidant cytoprotective activity of PSP against H2O2
      induced cell death. 

PMID- 24889550
TI  - Salvage stereotactic body radiotherapy for locally recurrent uterine cervix
      cancer at the pelvic sidewall: Feasibility and complication.
AB  - AIMS: To determine the feasibility of stereotactic body radiotherapy (SBRT) in
      patients with pelvic sidewall recurrence of uterine cervical cancer after radical
      hysterectomy or definitive radiotherapy. METHODS: We retrospectively reviewed 23
      patients with locally recurrent uterine cervical cancer limited to the pelvic
      sidewall who were treated with SBRT at our institution between January 2003 and
      May 2010. The SBRT dose ranged from 27 to 45 Gy (median, 39 Gy) in three
      fractions, and the fractional SBRT dose ranged from 9 to 15 Gy (median, 13 Gy).
      RESULTS: The 2-year overall survival, local progression-free survival and disease
      progression-free survival rates were 43%, 65% and 52%, respectively. Patients
      with small tumors (gross tumor volume <30 cm(3) ) had a significantly longer 2
      year overall survival rate and 2-year local progression-free survival rate than
      did patients with large tumors (overall survival rate: 89% vs 12%; P = 0.0001 and
      local progression-free survival: 85% vs 0%; P = 0.0199). There were three cases
      (13%) of severe toxicities (rectovaginal fistula). Pelvic pain relief was
      achieved in all patients. In particular, 10 of 14 patients (71%) achieved
      analgesic (nonsteroidal anti-inflammatory drug or narcotic) reduction of 50% or
      more from baseline. CONCLUSION: SBRT is a feasible treatment option for women
      with pelvic sidewall tumors from recurrent uterine cervical cancer, especially
      for small recurrent tumors. However, SBRT should be used carefully in the
      treatment of large tumors, as the incidence of severe late toxicity increases
      with the size of the tumor.

PMID- 24889551
TI  - Is soy intake related to age at onset of menarche? A cross-sectional study among
      adolescents with a wide range of soy food consumption.
AB  - BACKGROUND: Early onset of menarche may negatively influence the future health of
      adolescent girls. Several factors affect the timing of menarche but it is not
      clear if soy foods consumption around pubertal years plays a role; thus, we
      examined its relation to age at onset of menarche (AOM) in a high soy-consuming
      population. METHODS: We conducted a cross-sectional study on 339 girls ages 12-18
      years attending middle and high schools near two Seventh-day Adventist
      universities in California and Michigan using a web-based dietary questionnaire
      and physical development tool. Soy consumption (categorized as total soy, meat
      alternatives, tofu/traditional soy, and soy beverages) was estimated from the
      questionnaire, while AOM was self-reported. Data analyses included descriptive
      statistics, Cox proportional hazards ratios, Kaplan-Meier curves and Poisson
      regression with adjustment for relevant confounders. RESULTS: Mean (SD) intakes
      were: total soy,12.9 (14.4) servings/week; meat alternatives, 7.0 (8.9)
      servings/week; tofu/traditional soy foods, 2.1 (3.8) servings/week; soy
      beverages, 3.8 (6.3) servings/week. Mean AOM was 12.5 (1.4) y for those who
      reached menarche. Consumption of total soy and the 3 types of soy foods was not
      significantly associated with AOM and with the odds for early- or late-AOM.
      Adjustment for demographic and dietary factors did not change the results.
      CONCLUSION: Soy intake is not associated with AOM in a population of adolescent
      girls who have a wide range of, and relatively higher, soy intake than the
      general US population. Our finding suggests that the increasing popularity of soy
      in the US may not be associated with AOM.

PMID- 24889552
TI  - The use of cobalt-mediated cycloisomerisation of ynedinitriles in the synthesis
      of pyridazinohelicenes.
AB  - A cobalt-mediated [2+2+2] cycloisomerisation of ynedinitriles to helical
      pyridazines in good to high yields was developed. The construction of the
      pyridazine nucleus from one alkyne and two nitrile units is proposed to follow
      either a conventional organometallic mechanism or to be triggered by a single
      electron transfer from a Co(II) species. Various [5]-, [6]- and [7]helicene
      pyridazines were prepared. 

PMID- 24889554
TI  - Theoretical sampling.

PMID- 24889553
TI  - Do the omeprazole family compounds exert a protective effect against influenza
      like illness?
AB  - BACKGROUND: Infections by influenza viruses place a heavy burden on public health
      and economies worldwide. Although vaccines are the best weapons against
      influenza, antiviral drugs could offer an opportunity to alleviate the burden of
      influenza. Since omeprazole family compounds block the "proton pump", we
      hypothesized that they could interfere with the mechanism of fusion of the virus
      envelope and endosomal membrane, thereby hindering the M2 proton pump mechanism
      of influenza viruses. METHODS: A matched case-control study was performed in 2010
      2011 in Italy. Cases were subjects aged over 18 years with a diagnosis of
      Influenza-like Illness (ILI); 254 case-control pairs were recruited. A
      multivariable conditional logistic regression analysis was used to assess the
      association between the prevention of ILI and the administration of omeprazole
      family compounds. The interaction between omeprazole family compounds and
      influenza vaccination was also examined. RESULTS: After control for potential
      confounders, subjects treated with omeprazole family compounds displayed a lower
      risk of catching ILI (ORadj = 0.29, 95% CI: 0.15-0.52). The risk of ILI in
      unvaccinated non-OFC users was about six times than that in vaccinated OFC users.
      CONCLUSIONS: Although confirmation is necessary, these results suggest that
      omeprazole family compounds could be profitably used in the prevention of ILI.

PMID- 24889555
TI  - The MDM2 polymorphism SNP309 is associated with clinical characteristics and
      outcome in diffuse large B-cell lymphoma.
AB  - INTRODUCTION: The murine double minute 2 (MDM2) gene encodes a regulatory protein
      of the p53 pathway. A single nucleotide polymorphism (T to G change) at position
      309 (SNP309) in the promotor region of MDM2 affects the transcription activity of
      MDM2 and has been found to be a negative prognostic marker in several cancers.
      PATIENTS AND METHODS: In this study, the MDM2 SNP309 polymorphism was analysed in
      201 patients with diffuse large B-cell lymphoma and analysed in relation to
      clinical characteristics and prognosis. RESULTS: Patients homozygous for SNP309T
      had a significantly longer overall survival, lymphoma-specific survival and
      disease-free survival (P = 0.002; 0.004 and 0.006 respectively) compared to
      patients carrying a G allele. The longer overall survival was seen in the
      subgroup of patients not treated with Rituximab, however, not for Rituximab
      treated patients (P = 0.01 and 0.2 respectively). The group homozygous for the T
      allele also had lower age at diagnosis, a tendency towards lower aaIPI and a
      significantly lower proportion of patients with p53 aberrations compared to the
      group including at least one G allele. However, the survival differences
      persisted even after removal of cases with known p53 aberrations from the
      analysis. CONCLUSION: Polymorphism in MDM2 SNP309 could be correlated to some
      clinical characteristics and for patients not treated with immunotherapy, a G
      allele was correlated to poor survival, whereas no survival differences were
      found for patients treated with Rituximab. Herewith, we provide additional
      information about Diffuse large B-cell Lymphoma (DLBCL) biology and highlight the
      importance of evaluation of molecular markers in relation to treatment.

PMID- 24889556
TI  - Bronchoalveolar lavage fluid and blood natural killer and natural killer T-like
      cells in cryptogenic organizing pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Natural killer (NK) cells appear to be involved in the
      development of interstitial lung diseases (ILD). The purpose of this study was to
      investigate the involvement of NK and natural killer T (NKT)-like cells in two
      recognized cytotoxic ILD with systemic character, hypersensitivity pneumonitis
      (HP) and cryptogenic organizing pneumonia (COP), compared with idiopathic
      pulmonary fibrosis (IPF) and controls. METHODS: Bronchoalveolar lavage fluid
      (BALF) and peripheral blood (PBL) cells and lymphocyte subsets of 83 patients (26
      with COP, 19 with HP and 38 with IPF) and 10 controls were prospectively studied
      by flow cytometry. RESULTS: The percentage of NK and NKT-like cells was lower in
      BALF than in PBL in all patient groups and controls. Patients with COP presented
      with statistically significantly higher NK and NKT-like cell counts in BALF
      compared with controls (P = 0.044 and P = 0.05 respectively) and IPF (P = 0.049
      and P = 0.045 respectively). BALF NKT-like cell count correlated with PBL NKT
      like cell count only in COP (r = 0.627, P = 0.002). In addition, a significant
      positive correlation between BALF NKT-like cell and PBL cytotoxic T CD8+ cell
      count was observed in COP (r = 0.562, P = 0.006) but not in HP, IPF or controls.
      CONCLUSIONS: Our study provides for the first time evidence for the implication
      of NKT-like cells in the pathogenesis of COP, as part of both localized and
      systemic cytotoxicity.

PMID- 24889557
TI  - Organotypic culture to assess cell adhesion, growth and alignment of different
      organs on silk fibroin.
AB  - Glass sheets covered with aligned electrospun silk fibroin (Bombyx mori) were
      compared to tissue culture-treated Thermanox(r) coverslips, using an organotypic
      culture method. Different chick embryo organ behaviours were analysed in terms of
      circularity, cell growth and cell adhesion after being cultivated in contact with
      these two materials. The circularity (cell layer shape corresponding to the trend
      of the biomaterials to induce a specific directionality) depends on the organ
      used when in contact with silk fibroin. This biomaterial induced higher cell
      adhesion (kidney) or lower cell adhesion (spine) compared to Thermanox. Cell
      growth, represented by the cell layer area (mm2 ), was also drastically reduced
      (gonad) or increased (blood vessel) on the silk fibroin. Organotypic culture is a
      rapid, cost effective and relatively simple method to evaluate different
      parameters, allowing prescreening of morphology and cytocompatibility to select
      the appropriate applications for new biomaterials. In the present study we
      compared the morphology of different organotypic cultures on orientated silk and
      Thermanox as growth supports to rapidly evaluate the benefit of a silk-based
      biomaterial for tissue engineering. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24889558
TI  - Associations between human TRIM22 gene expression and the response to combination
      therapy with Peg-IFNalpha-2a and ribavirin in Iranian patients with chronic
      hepatitis C.
AB  - Interferons are able to exert an antiviral effect against hepatitis C virus (HCV)
      infection via induction of interferon-stimulated genes (ISGs). This study tested
      whether differential expression of an important ISG with antiviral properties,
      tripartite motif 22 (TRIM22), correlates with a response to Peg-IFNalpha-2a/RBV
      combination therapy in treatment-naive patients with chronic hepatitis C. A total
      of 32 patients with chronic hepatitis C were enrolled in this study and received
      standard Peg-IFNalpha-2a/RBV combination therapy. HCV viral load was measured
      during treatment, at the end of treatment, and 6 months later to determine the
      treatment outcome. Quantitative real-time PCR was used to assess the expression
      levels of TRIM22 in peripheral blood mononuclear cells (PBMCs) of the patients
      before antiviral therapy. Of the 32 patients, 26 (81.3%) were males. In this
      study, there were 16 (50%) individuals with a sustained virologic response (SVR),
      and a virologic relapse was observed in the remaining half of the subjects.
      Testing for the presence of genomic HCV RNA in blood during therapy revealed a
      rapid virologic response (RVR) in 10 (31.2%) and a partial and complete early
      virologic response (EVR) in 8 (25%) and 24 (75%) of the cases, respectively.
      TRIM22 mRNA levels were significantly higher in patients with a sustained
      virologic response than in relapsers (P = 0.002) and in patients with a rapid
      virologic response than in the others (P = 0.040). No statistically significant
      difference was seen in the expression of TRIM22 between patients with a partial
      early virologic response and a complete early virologic response. This study
      showed that pretreatment upregulation of TRIM22 may be associated with
      responsiveness to Peg-IFNalpha-2a/RBV combination therapy.

PMID- 24889559
TI  - Genome-scale metabolic reconstruction and constraint-based modelling of the
      Antarctic bacterium Pseudoalteromonas haloplanktis TAC125.
AB  - The Antarctic strain Pseudoalteromonas haloplanktis TAC125 is one of the model
      organisms of cold-adapted bacteria and is currently exploited as a new
      alternative expression host for numerous biotechnological applications. Here, we
      investigated several metabolic features of this strain through in silico
      modelling and functional integration of -omics data. A genome-scale metabolic
      model of P. haloplanktis TAC125 was reconstructed, encompassing information on
      721 genes, 1133 metabolites and 1322 reactions. The predictive potential of this
      model was validated against a set of experimentally determined growth rates and a
      large dataset of growth phenotypic data. Furthermore, evidence synthesis from
      proteomics, phenomics, physiology and metabolic modelling data revealed possible
      drawbacks of cold-dependent changes in gene expression on the overall metabolic
      network of P. haloplanktis TAC125. These included, for example, variations in its
      central metabolism, amino acid degradation and fatty acid biosynthesis. The
      genome-scale metabolic model described here is the first one reconstructed so far
      for an Antarctic microbial strain. It allowed a system-level investigation of
      variations in cellular metabolic fluxes following a temperature downshift. It
      represents a valuable platform for further investigations on P. haloplanktis
      TAC125 cellular functional states and for the design of more focused strategies
      for its possible biotechnological exploitation. 

PMID- 24889560
TI  - A new kid on the block.

PMID- 24889561
TI  - GP commissioning: the first year.

PMID- 24889563
TI  - Medicine: a rethink? Are entrants to the profession and the way it is organised
      fit for purpose?
AB  - The health burden in most countries has changed. Although acute care is needed
      for trauma, acute illness and exacerbations of chronic disease, most of the
      burden is now long term. These patients need different approaches, with more
      emphasis upon supporting self-management, enhancing lifestyle changes, aiding
      compliance by shared decision-making and providing more convenient follow-up that
      appreciates the likelihood of multimorbidity. Integrated care will increasingly
      be offered from within the community. The current hospital- and doctor-centric
      focus needs to change to one where specialists work in the community as much as
      in hospitals and share this different type of care with others. For potential
      future doctors, the scientific basis of medicine will still underpin their unique
      role in diagnosis and prescribing, but they will need to understand these other
      changes and to be selected according to attributes compatible with their future
      role, and then be trained and assessed accordingly. 

PMID- 24889562
TI  - How to improve our health services.

PMID- 24889564
TI  - Licensing procedures and registration of medical doctors in the European Union.
AB  - The current proposals to update the European Union (EU) directive on professional
      qualifications will have potentially important implications for health
      professions. Yet those discussing it will struggle to find basic information on
      key issues such as licensing and registration of physicians in different
      countries. A survey was conducted among national experts in 14 EU member states,
      supplemented by literature and independent expert review. The questionnaire
      covered five components of licensing and registration: (1) definitions, (2)
      regulatory basis, (3) governance, (4) the process of registration and (5) flow
      and quantity of applications. We identify seven areas of concern: (1) the meaning
      of terminology, which is inconsistent; (2) the role of language assessments and
      the responsibility for them; (3) whether approval to practise should be lifelong
      or time limited, subject to periodic assessment; (4) the need for improved
      systems to identify those deemed no longer fit to practise in one member state;
      (5) the complexity of processes for graduates from non-EU/European Economic Area
      (EAA) countries; (6) public access to registers; and (7) transparency of systems
      of governance. The systems of licensing and registration of doctors in Europe
      have developed within specific national contexts and vary widely. This creates
      inevitable problems in the context of free movement of professionals and
      increasing mobility. 

PMID- 24889565
TI  - Dispelling myths about coagulation abnormalities in internal medicine.
AB  - The clotting screen is an 'integral' part of the routine blood tests in most
      medical wards. It is likely that only with the increasing requests for
      prothrombin time and activated partial thromboplastin time are abnormal results
      noted. Interpretation of these results requires good understanding of the
      coagulation system and problems with the laboratory analysis. Due to variable
      understanding of this complex system, many misconceptions have arisen in relation
      to the clinical effects expected from abnormal clotting screens. Some of these
      are discussed with considerations of appropriate management in those situations. 

PMID- 24889567
TI  - The Ambulatory Care Unit at Derriford Hospital.
AB  - Ambulatory emergency care (AEC) is an essential component of any acute medical
      unit (AMU). This statement is predicated on the clinical and financial benefits
      it confers. In this article, the author outlines the implementation of the
      Ambulatory Care Unit at Derriford Hospital and the first 6 months of service
      provision. The initial data collated demonstrates the impact the service has had
      locally on patient care and experience. It recommends ambulatory care as driver
      of better patient flow and enhanced patient experience within the AMU. 

PMID- 24889566
TI  - Should they have a percutaneous endoscopic gastrostomy? the importance of
      assessing decision-making capacity and the central role of a multidisciplinary
      team.
AB  - Decisions about percutaneous endoscopic gastrostomy (PEG) can be clinically and
      ethically challenging, particularly when patients lack decision-making capacity.
      As the age of the UK population rises, with the associated increase in prevalence
      of dementias and neurodegenerative diseases, it is becoming an increasingly
      important issue for clinicians. The recent review and subsequent withdrawal of
      the Liverpool Care Pathway highlighted feeding as a particular area of concern.
      The authors undertook a 1-year retrospective review of individuals referred to
      the feeding issues multidisciplinary team (FIMDT) at Addenbrooke's Hospital,
      Cambridge, UK, in 2011. The majority of patients referred (n = 158) had a primary
      diagnosis of cancer (44%). The second largest group was those who had had a
      stroke or brain haemorrhage (13%). Twenty-eight per cent of patients had no, or
      uncertain, decision-making capacity on at least one occasion during decision
      making. There are reflections on the role of a multidisciplinary team in the
      process of decision-making for these complex patients. 

PMID- 24889568
TI  - Cerebral amyloid angiopathy: a transient ischaemic attack mimic.
AB  - Cerebral amyloid angiopathy is a commonly occurring condition that is not
      familiar to most clinicians. A common presenting feature may be transient focal
      neurological symptoms leading to the potential for clinical misdiagnosis as
      transient ischaemic attack. This may result in the inappropriate use of anti
      platelets and anticoagulants or radiological misdiagnosis. It is also being
      increasingly recognised as an important cause of spontaneous intracerebral
      haemorrhage and cognitive impairment in the elderly. Cerebral amyloid angiopathy
      can be diagnosed based on clinical and radiological findings, but clinicians need
      a high index of suspicion to ensure appropriate investigations are requested. In
      this article we aim to cover the pathophysiology, clinical findings, radiological
      appearances and approach to management of cerebral amyloid angiopathy. 

PMID- 24889569
TI  - The management of patients presenting with hypernatraemia: is aggressive
      management appropriate?
AB  - Hypernatraemia is a common finding among patients presenting to hospital. The aim
      of this observational study was to discover what types of patients presented with
      hypernatraemia and whether they were appropriately managed. The management of
      hypernatraemia was audited against common standards of care. Hypernatraemia at
      presentation carries a poor prognosis and in this study management of
      hypernatraemia was found to be done poorly, possibly because for many patients
      aggressive management was deemed inappropriate. The majority of patients who
      present with hypernatraemia are older, dependent and/or suffer from cognitive
      impairment. Many of these patients do not have a reversible cause for their
      hypernatraemia. These patients need to be recognised, ideally in the community,
      so that inappropriate admission can be avoided, but also on presentation to
      hospital so that appropriate care, which may be end-of-life care, can be
      provided. 

PMID- 24889570
TI  - Inter-rater agreement of observable and elicitable neurological signs.
AB  - This paper reports on a study that aimed to assess the inter-rater agreement of
      observable neurological signs in the upper and lower limbs (eg inspection, gait,
      cerebellar tests and coordination) and elicitable signs (eg tone, strength,
      reflexes and sensation). Thirty patients were examined by two neurology doctors,
      at least one of whom was a consultant. The doctors' findings were recorded on a
      standardised pro forma. Inter-rater agreement was assessed using the kappa
      (kappa) statistic, which is chance corrected. There was significantly better
      agreement between the two doctors for observable than for elicitable signs (mean
      +/- standard deviation [SD] kappa, 0.70 +/- 0.17 vs 0.41 +/- 0.22, p = 0.002).
      Almost perfect agreement was seen for cerebellar signs and inspection (a
      combination of speed of movement, muscle bulk, wasting and tremor); substantial
      agreement for strength, gait and coordination; moderate agreement for tone and
      reflexes; and only fair agreement for sensation. The inter-rater agreement is
      therefore better for observable neurological signs than for elicitable signs,
      which may be explained by the additional skill and cooperation required to elicit
      rather than just observe clinical signs. These findings have implications for
      clinical practice, particularly in telemedicine, and highlight the need for
      standardisation of the neurological examination.

PMID- 24889571
TI  - Consultant supervision of trainees seeing inpatient ward referrals - a cause for
      concern?
AB  - The adequate supervision of trainee doctors seeing ward referrals is critical to
      the quality of patient care and medical training. This survey assessed the level
      and nature of supervision of trainees in neurology and comparable specialities.
      123 neurology specialty registrars from nine deaneries across the UK and 81
      dermatology, rheumatology and infectious disease specialty registrars from the
      London deanery completed the survey. Only 11% of first year neurology and 21% of
      first year non-neurology registrars reported that the most common method of
      supervision when seeing ward referrals was for consultants to see ward referrals
      with them. The remaining first year neurology and non-neurology registrars
      reported being primarily supervised by discussing cases with consultant (62% and
      37% respectively) or being asked to contact a consultant if help was needed (35%
      and 42% respectively). The lack of adequate supervision of junior trainees seeing
      ward referrals has significant implications for both patient safety and training.

PMID- 24889572
TI  - Care of adolescents and young adults with diabetes - much more than transitional
      care: a personal view.
AB  - There is increasing recognition that type 1 diabetes mellitus (T1DM) acquired in
      childhood and adolescence requires a sophisticated approach that facilitates
      better self-management through adherence to generic principles in managing
      chronic disease in this age group, allied to the complex clinical needs of
      managing T1DM and related conditions. Transitional care should be seen as a
      process over time supported by both paediatric and adult diabetologists within a
      multidisciplinary team, given the complementary skills that can be brought to
      bear. Undoubtedly, there is a need for more effective training of all healthcare
      professionals working in this service. However, the accumulation of older
      teenagers over time and new diagnoses in those aged 19 years or more confirms
      that a new paradigm is necessary for the successful care of young adults beyond
      transitional care. Traditional clinical models will often not work for those in
      employment and higher education, with evidence that ongoing engagement following
      transfer to adult services often ceases. The alarming evidence of progressive
      complications in T1DM of longer duration in patients under the age of 40 years is
      a wake-up call to transform the care of this most vulnerable group.

PMID- 24889573
TI  - Multidrug-resistant and extensively drug-resistant tuberculosis: a review of
      current concepts and future challenges.
AB  - Multidrug-resistant and extensively drug-resistant tuberculosis are recent global
      health issues, which makes tuberculosis - after the success of short course
      treatment during the second half of the last century - a major health challenge.
      Globalisation, health inequalities, competing economic interests and political
      instability contribute substantially to the spread of drug-resistant strains,
      which are associated with high rates of morbidity and mortality. Issues such as
      increasing transmission of drug-resistant strains, poor diagnostic coverage and a
      lengthy, toxic treatment need to be overcome by innovative approaches to
      tuberculosis control, prevention, diagnostics and treatment. This review
      addresses recent developments and future concepts. 

PMID- 24889574
TI  - Defining the neural basis of appetite and obesity: from genes to behaviour.
AB  - Obesity represents one of the biggest public health challenges facing us today.
      Urbanisation, sedentary lifestyles and the availability of inexpensive, highly
      palatable foods have promoted the increasing prevalence of obesity over the past
      30 years. However, some people gain weight more easily than others, and there is
      strong evidence that, within a given environment, this variance in body weight is
      influenced by genetic factors. This article discusses how genetic studies have
      contributed to our understanding of the mechanisms involved in the regulation of
      body weight. We now understand that weight is regulated by neural mechanisms that
      regulate appetite and energy expenditure and that disruption of these pathways
      can result in severe obesity in some patients. These studies provide a framework
      for investigating patients and ultimately may guide the development of more
      rational, targeted therapies for genetically susceptible individuals with severe
      obesity.

PMID- 24889575
TI  - Conscientious care for the unconscious patient: new guidance from the Royal
      College of Physicians.
AB  - Patients who remain unconscious and unaware after a brain insult challenge
      healthcare. Clinicians are faced with a clinical situation often outside their
      usual experience. Organisations are faced with practical issues concerning
      resource use. And people, especially family and friends, are faced with moral,
      legal and philosophical questions that have no easy answers. This conference
      launched national guidelines that should assist clinical teams and organisations,
      and should ensure that all patients and families receive a good quality service. 

PMID- 24889576
TI  - Palliative care for frail older people.

PMID- 24889577
TI  - Discussing and planning care for people approaching the end of their life.

PMID- 24889578
TI  - An innovative development programme for consultants to improve patient care in
      the last months of life.

PMID- 24889579
TI  - Managing pain in advanced illness.

PMID- 24889580
TI  - Managing breathlessness in advanced disease.

PMID- 24889581
TI  - CME Palliative medicine SAQs (86425): self-assessment questionnaire.

PMID- 24889582
TI  - Lesson of the month 1: sudden onset postural livedo reticularis, cyanotic toes
      and multiorgan failure.
AB  - Cholesterol embolisation syndrome (CES) is a rare but serious disease with high
      mortality caused by the formation of an embolus made up of cholesterol crystals
      from atherosclerotic plaques. Its clinical presentation is usually initially
      insidious and it often remains unrecognised because of its non-specific clinical
      presentation, which can cause delays in treatment and high mortality. The most
      common physical symptoms are cutaneous. We present a lethal case of CES to
      increase the awareness about this serious condition. 

PMID- 24889583
TI  - Lesson of the month 2: toxic shock syndrome.
AB  - Toxic shock syndrome (TSS) represents a fascinating example of immune activation
      caused by infection resulting in a dramatic and challenging clinical syndrome.
      TSS is commonly associated with tampon use and still causes significant morbidity
      and mortality in young healthy women. A misconception is that TSS presents with a
      skin rash and only occurs in women and children; however, it can occur in males
      and can present without skin changes. TSS presents initially as a febrile illness
      and within a few hours can progress to severe hypotension and multiple organ
      failure (MOF). Staphylococcus aureus and group A beta haemolytic streptococcus
      (GABHS) can secrete toxins from a small or hidden focus of infection and hence
      blood culture and sensitivity (C+S) tests can be negative, thereby making
      diagnosing this condition challenging. Clindamycin is superior to penicillin in
      the treatment of this condition and significantly decreases the mortality rate in
      TSS. However, there is also an important role for intravenous immunoglobulins
      (IVIG). Early intensive care unit (ICU) as well as surgical team involvement (in
      selected cases) is required to avoid mortality which may approach 70%. 

PMID- 24889584
TI  - Painful swollen thigh in a patient with poorly controlled diabetes.

PMID- 24889586
TI  - Axel Munthe and the story of San Michele: the perils of being a 'fashionable'
      doctor.

PMID- 24889588
TI  - Non-selective beta-adrenoceptor blockers in patients with decompensated liver
      disease.

PMID- 24889589
TI  - A very unusual headache.

PMID- 24889590
TI  - Beware the normal angiogram.

PMID- 24889591
TI  - Cardiology registrars and permanent pacemaker complication rates.

PMID- 24889592
TI  - Palliative care of chronic progressive lung disease.

PMID- 24889593
TI  - Palliative care of chronic progressive lung disease.

PMID- 24889595
TI  - How frequently are bedside glucose levels measured in hospital inpatients on
      glucocorticoid treatment?

PMID- 24889594
TI  - Clinical stories are necessary for drug safety.

PMID- 24889596
TI  - Laminectomy retractor: a useful tool for redo sternotomy.
AB  - Sternal re-entry represents a critical step during redo cardiac surgery. We
      describe a simple method that relies on opening of the posterior table of the
      sternum with a laminectomy retractor after dividing the anterior table with an
      oscillating saw.

PMID- 24889597
TI  - PCBP1 is an important mediator of TGF-beta-induced epithelial to mesenchymal
      transition in gall bladder cancer cell line GBC-SD.
AB  - Gall bladder carcinoma (GBC) is the seventh most common cancer across the globe
      and the most common malignancy of the biliary tract. Most GBC related deaths
      occur due to secondary progression and metastasis to distant organs. Epithelial
      mesenchymal transition (EMT) is an important pre-requisite for tumor metastasis,
      however its mechanism in GBC has not yet been defined. Using the GBC-SD cell
      line, we have uncovered an important mediator, poly r(C) binding protein-1
      (PCBP1), of transforming growth factor-beta (TGF-beta)-induced EMT in GBC. Our
      results show that TGF-beta treatment resulted in PCBP1 phosphorylation in
      accordance with similar observation in other model systems. We further showed
      through gain- and loss-of-function assays that PCBP1 expression levels regulate
      the capacity of GBC-SD cells to migrate and invade in vitro. Finally, our results
      showed that PCBP1 expression levels also regulate generation of CD44(+)CD24(-)
      progenitor cell population in GBC-SD cells after TGF-beta treatment.
      Cumulatively, our results indicate, pending further validation, that PCBP1 might
      be a prognostic marker for GBC metastasis. 

PMID- 24889598
TI  - Single case methodology in neurobehavioural rehabilitation: preliminary findings
      on biofeedback in the treatment of challenging behaviour.
AB  - The use of single-case methodology (SCM) in brain injury rehabilitation is
      described and contrasted with other methodologies. SCM is optimal when attempting
      to meet highly individual presentations or to trial innovative solutions.
      Portable biofeedback is a potentially effective means of helping persons with
      brain injury to recognise and regulate emotional states. Emotional dysregulation,
      associated with disinhibition on tests of executive function, is hypothesised to
      underpin aggressive challenging behaviour and may be amenable to feedback on
      heart rate variability, a marker for stress. Two case studies of a novel
      biofeedback intervention, emWave2, to address aggression directed towards the
      self and towards others are presented. Data from two A-B designs were analysed
      using the non-overlap all pairs (NAP) statistical method. Clinical significance
      of outcome is reported in both cases but only Case 2 reached statistical
      significance. The discussion highlights limitations of the methodology. Results
      are discussed in relation to the device helping participants differentiate the
      physiological state associated with stress. The future application of wearable
      physiological sensing and feedback systems is explored. 

PMID- 24889599
TI  - Combination of blood tests for significant fibrosis and cirrhosis improves the
      assessment of liver-prognosis in chronic hepatitis C.
AB  - BACKGROUND: Recent longitudinal studies have emphasised the prognostic value of
      noninvasive tests of liver fibrosis and cross-sectional studies have shown their
      combination significantly improves diagnostic accuracy. AIM: To compare the
      prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if
      test combination improves the liver-prognosis assessment in chronic hepatitis C
      (CHC). METHODS: A total of 373 patients with compensated CHC, liver biopsy
      (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore,
      FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related
      events (SLRE) and liver-related deaths were recorded during follow-up (started
      the day of biopsy). RESULTS: During the median follow-up of 9.5 years (3508
      person-years), 47 patients had a SLRE and 23 patients died from liver-related
      causes. For the prediction of first SLRE, most blood tests allowed higher
      prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)]
      with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002),
      FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P =
      0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained
      viral response as independent predictors of first SLRE. CirrhoMeter was the only
      independent predictor of liver-related death. The combination of FibroMeter and
      CirrhoMeter classifications into a new FM/CM classification improved the liver
      prognosis assessment compared to Metavir F staging or single tests by identifying
      five subgroups of patients with significantly different prognoses. CONCLUSIONS:
      Some blood fibrosis tests are more accurate than liver biopsy for determining
      liver prognosis in CHC. A new combination of two complementary blood tests, one
      targeted for fibrosis and the other for cirrhosis, optimises assessment of liver
      prognosis.

PMID- 24889600
TI  - Total synthesis of 7- and 8-oxygenated pyrano[3,2-a]carbazole and pyrano[2,3
      a]carbazole alkaloids via boronic acid-catalyzed annulation of the pyran ring.
AB  - The boronic acid-catalyzed annulation of citral opens up a short route to
      oxygenated cyclized monoterpenoid pyranocarbazole alkaloids. Thus, murrayamine-D
      is available in only three steps and 55% overall yield from the corresponding
      carbazole precursor. 

PMID- 24889601
TI  - Experimental evidence of massive-scale emotional contagion through social
      networks.
AB  - Emotional states can be transferred to others via emotional contagion, leading
      people to experience the same emotions without their awareness. Emotional
      contagion is well established in laboratory experiments, with people transferring
      positive and negative emotions to others. Data from a large real-world social
      network, collected over a 20-y period suggests that longer-lasting moods (e.g.,
      depression, happiness) can be transferred through networks [Fowler JH, Christakis
      NA (2008) BMJ 337:a2338], although the results are controversial. In an
      experiment with people who use Facebook, we test whether emotional contagion
      occurs outside of in-person interaction between individuals by reducing the
      amount of emotional content in the News Feed. When positive expressions were
      reduced, people produced fewer positive posts and more negative posts; when
      negative expressions were reduced, the opposite pattern occurred. These results
      indicate that emotions expressed by others on Facebook influence our own
      emotions, constituting experimental evidence for massive-scale contagion via
      social networks. This work also suggests that, in contrast to prevailing
      assumptions, in-person interaction and nonverbal cues are not strictly necessary
      for emotional contagion, and that the observation of others' positive experiences
      constitutes a positive experience for people.

PMID- 24889602
TI  - Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain
      activity in a mouse model of schizophrenia.
AB  - Maternal infection during pregnancy increases the risk for schizophrenia in
      offspring. In rodent models, maternal immune activation (MIA) yields offspring
      with schizophrenia-like behaviors. None of these behaviors are, however, specific
      to schizophrenia. The presence of hallucinations is a key diagnostic symptom of
      schizophrenia. In mice, this symptom can be defined as brain activation in the
      absence of external stimuli, which can be mimicked by administration of
      hallucinogens. We find that, compared with controls, adult MIA offspring display
      an increased stereotypical behavioral response to the hallucinogen 2,5-dimethoxy
      4-iodoamphetamine (DOI), an agonist for serotonin receptor 2A (5-HT2AR). This may
      be explained by increased levels of 5-HT2AR and downstream signaling molecules in
      unstimulated MIA prefrontal cortex (PFC). Using manganese-enhanced magnetic
      resonance imaging to identify neuronal activation elicited by DOI administration,
      we find that, compared with controls, MIA offspring exhibit a greater manganese
      (Mn(2+)) accumulation in several brain areas, including the PFC, thalamus, and
      striatum. The parafascicular thalamic nucleus, which plays the role in the
      pathogenesis of hallucinations, is activated by DOI in MIA offspring only.
      Additionally, compared with controls, MIA offspring demonstrate higher DOI
      induced expression of early growth response protein 1, cyclooxygenase-2, and
      brain-derived neurotrophic factor in the PFC. Chronic treatment with the 5-HT2AR
      antagonist ketanserin reduces DOI-induced head twitching in MIA offspring. Thus,
      the MIA mouse model can be successfully used to investigate activity induced by
      DOI in awake, behaving mice. Moreover, manganese-enhanced magnetic resonance
      imaging is a useful, noninvasive method for accurately measuring this type of
      activity. 

PMID- 24889603
TI  - In situ selectivity profiling and crystal structure of SML-8-73-1, an active site
      inhibitor of oncogenic K-Ras G12C.
AB  - Directly targeting oncogenic V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
      (K-Ras) with small-molecule inhibitors has historically been considered
      prohibitively challenging. Recent reports of compounds that bind directly to the
      K-Ras G12C mutant suggest avenues to overcome key obstacles that stand in the way
      of developing such compounds. We aim to target the guanine nucleotide (GN)
      binding pocket because the natural contents of this pocket dictate the signaling
      state of K-Ras. Here, we characterize the irreversible inhibitor SML-8-73-1
      (SML), which targets the GN-binding pocket of K-Ras G12C. We report a high
      resolution X-ray crystal structure of G12C K-Ras bound to SML, revealing that the
      compound binds in a manner similar to GDP, forming a covalent linkage with Cys
      12. The resulting conformation renders K-Ras in the open, inactive conformation,
      which is not predicted to associate productively with or activate downstream
      effectors. Conservation analysis of the Ras family GN-binding pocket reveals
      variability in the side chains surrounding the active site and adjacent regions,
      especially in the switch I region. This variability may enable building
      specificity into new iterations of Ras and other GTPase inhibitors. High
      resolution in situ chemical proteomic profiling of SML confirms that SML
      effectively discriminates between K-Ras G12C and other cellular GTP-binding
      proteins. A biochemical assay provides additional evidence that SML is able to
      compete with millimolar concentrations of GTP and GDP for the GN-binding site. 

PMID- 24889604
TI  - Visual account of protein investment in cellular functions.
AB  - Proteomics techniques generate an avalanche of data and promise to satisfy
      biologists' long-held desire to measure absolute protein abundances on a genome
      wide scale. However, can this knowledge be translated into a clearer picture of
      how cells invest their protein resources? This article aims to give a broad
      perspective on the composition of proteomes as gleaned from recent quantitative
      proteomics studies. We describe proteomaps, an approach for visualizing the
      composition of proteomes with a focus on protein abundances and functions. In
      proteomaps, each protein is shown as a polygon-shaped tile, with an area
      representing protein abundance. Functionally related proteins appear in adjacent
      regions. General trends in proteomes, such as the dominance of metabolism and
      protein production, become easily visible. We make interactive visualizations of
      published proteome datasets accessible at www.proteomaps.net. We suggest that
      evaluating the way protein resources are allocated by various organisms and cell
      types in different conditions will sharpen our understanding of how and why cells
      regulate the composition of their proteomes. 

PMID- 24889605
TI  - Differential role of nonhomologous end joining factors in the generation, DNA
      damage response, and myeloid differentiation of human induced pluripotent stem
      cells.
AB  - Nonhomologous end-joining (NHEJ) is a key pathway for efficient repair of DNA
      double-strand breaks (DSBs) and V(D)J recombination. NHEJ defects in humans cause
      immunodeficiency and increased cellular sensitivity to ionizing irradiation (IR)
      and are variably associated with growth retardation, microcephaly, and
      neurodevelopmental delay. Repair of DNA DSBs is important for reprogramming of
      somatic cells into induced pluripotent stem cells (iPSCs). To compare the
      specific contribution of DNA ligase 4 (LIG4), Artemis, and DNA-protein kinase
      catalytic subunit (PKcs) in this process and to gain insights into phenotypic
      variability associated with these disorders, we reprogrammed patient-derived
      fibroblast cell lines with NHEJ defects. Deficiencies of LIG4 and of DNA-PK
      catalytic activity, but not Artemis deficiency, were associated with markedly
      reduced reprogramming efficiency, which could be partially rescued by genetic
      complementation. Moreover, we identified increased genomic instability in LIG4
      deficient iPSCs. Cell cycle synchronization revealed a severe defect of DNA
      repair and a G0/G1 cell cycle arrest, particularly in LIG4- and DNA-PK
      catalytically deficient iPSCs. Impaired myeloid differentiation was observed in
      LIG4-, but not Artemis- or DNA-PK-mutated iPSCs. These results indicate a
      critical importance of the NHEJ pathway for somatic cell reprogramming, with a
      major role for LIG4 and DNA-PKcs and a minor, if any, for Artemis. 

PMID- 24889607
TI  - Local versus basin-scale limitation of marine nitrogen fixation.
AB  - Nitrogen (N) fixation by diazotrophic plankton is the primary source of this
      crucial nutrient to the ocean, but the factors limiting its rate and distribution
      are controversial. According to one view, the ecological niche of diazotrophs is
      primarily controlled by the ocean through internally generated N deficits that
      suppress the growth of their competitors. A second view posits an overriding
      limit from the atmosphere, which restricts diazotrophs to regions where dust
      deposition satisfies their high iron (Fe) requirement, thus separating N sources
      from sinks at a global scale. Here we use multiple geochemical signatures of N2
      fixation to show that the Fe limitation of diazotrophs is strong enough to
      modulate the regional distribution of N2 fixation within ocean basins-
      particularly the Fe-poor Pacific--but not strong enough to influence its
      partition between basins, which is instead governed by rates of N loss. This
      scale-dependent limitation of N2 fixation reconciles local observations of Fe
      stress in diazotroph communities with an inferred spatial coupling of N sources
      and sinks. Within this regime of intermediate Fe control, the oceanic N reservoir
      would respond only weakly to enhanced dust fluxes during glacial climates, but
      strongly to the reduced fluxes hypothesized under anthropogenic climate warming.

PMID- 24889608
TI  - Multiplex genome editing by natural transformation.
AB  - Editing bacterial genomes is an essential tool in research and synthetic biology
      applications. Here, we describe multiplex genome editing by natural
      transformation (MuGENT), a method for accelerated evolution based on the
      cotransformation of unlinked genetic markers in naturally competent
      microorganisms. We found that natural cotransformation allows scarless genome
      editing at unprecedented frequencies of ~50%. Using DNA substrates with
      randomized nucleotides, we found no evidence for bias during natural
      cotransformation, indicating that this method can be used for directed evolution
      studies. Furthermore, we found that natural cotransformation is an effective
      method for multiplex genome editing. Because MuGENT does not require selection at
      edited loci in cis, output mutant pools are highly complex, and strains may have
      any number and combination of the multiplexed genome edits. We demonstrate the
      utility of this technique in metabolic and phenotypic engineering by optimizing
      natural transformation in Vibrio cholerae. This was accomplished by
      combinatorially editing the genome via gene deletions and promoter replacements
      and by tuning translation initiation of five genes involved in the process of
      natural competence and transformation. MuGENT allowed for the generation of a
      complex mutant pool in 1 wk and resulted in the selection of a genetically edited
      strain with a 30-fold improvement in natural transformation. We also demonstrate
      the efficacy of this technique in Streptococcus pneumoniae and highlight the
      potential for MuGENT to be used in multiplex genetic interaction analysis. Thus,
      MuGENT is a broadly applicable platform for accelerated evolution and genetic
      interaction studies in diverse naturally competent species. 

PMID- 24889606
TI  - NAD+ and SIRT3 control microtubule dynamics and reduce susceptibility to
      antimicrotubule agents.
AB  - Nicotinamide adenine dinucleotide (NAD(+)) is an endogenous enzyme cofactor and
      cosubstrate that has effects on diverse cellular and physiologic processes,
      including reactive oxygen species generation, mitochondrial function, apoptosis,
      and axonal degeneration. A major goal is to identify the NAD(+)-regulated
      cellular pathways that may mediate these effects. Here we show that the dynamic
      assembly and disassembly of microtubules is markedly altered by NAD(+).
      Furthermore, we show that the disassembly of microtubule polymers elicited by
      microtubule depolymerizing agents is blocked by increasing intracellular NAD(+)
      levels. We find that these effects of NAD(+) are mediated by the activation of
      the mitochondrial sirtuin sirtuin-3 (SIRT3). Overexpression of SIRT3 prevents
      microtubule disassembly and apoptosis elicited by antimicrotubule agents and
      knockdown of SIRT3 prevents the protective effects of NAD(+) on microtubule
      polymers. Taken together, these data demonstrate that NAD(+) and SIRT3 regulate
      microtubule polymerization and the efficacy of antimicrotubule agents. 

PMID- 24889609
TI  - 11beta-HSD1 is the major regulator of the tissue-specific effects of circulating
      glucocorticoid excess.
AB  - The adverse metabolic effects of prescribed and endogenous glucocorticoid (GC)
      excess, Cushing syndrome, create a significant health burden. We found that
      tissue regeneration of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1), rather than circulating delivery, is critical to developing the phenotype
      of GC excess; 11beta-HSD1 KO mice with circulating GC excess are protected from
      the glucose intolerance, hyperinsulinemia, hepatic steatosis, adiposity,
      hypertension, myopathy, and dermal atrophy of Cushing syndrome. Whereas liver
      specific 11beta-HSD1 KO mice developed a full Cushingoid phenotype, adipose
      specific 11beta-HSD1 KO mice were protected from hepatic steatosis and
      circulating fatty acid excess. These data challenge our current view of GC
      action, demonstrating 11beta-HSD1, particularly in adipose tissue, is key to the
      development of the adverse metabolic profile associated with circulating GC
      excess, offering 11beta-HSD1 inhibition as a previously unidentified approach to
      treat Cushing syndrome. 

PMID- 24889610
TI  - Photoinduced transformations of stiff-stilbene-based discrete metallacycles to
      metallosupramolecular polymers.
AB  - Control over structural transformations in supramolecular entities by external
      stimuli is critical for the development of adaptable and functional soft
      materials. Herein, we have designed and synthesized a dipyridyl donor containing
      a central Z-configured stiff-stilbene unit that self-assembles in the presence of
      two 180 degrees  di-Pt(II) acceptors to produce size-controllable discrete
      organoplatinum(II) metallacycles with high efficiency by means of the directional
      bonding approach. These discrete metallacycles undergo transformation into
      extended metallosupramolecular polymers upon the conformational switching of the
      dipyridyl ligand from Z-configured (0 degrees ) to E-configured (180 degrees )
      when photoirradiated. This transformation is accompanied by interesting
      morphological changes at nanoscopic length scales. The discrete metallacycles
      aggregate to spherical nanoparticles that evolve into long nanofibers upon
      polymer formation. These fibers can be reversibly converted to cyclic oligomers
      by changing the wavelength of irradiation, which reintroduces Z-configured
      building blocks owing to the reversible nature of stiff-stilbene
      photoisomerization. The design strategy defined here represents a novel self
      assembly pathway to deliver advanced supramolecular assemblies by means of
      photocontrol. 

PMID- 24889611
TI  - Engineering of a red-light-activated human cAMP/cGMP-specific phosphodiesterase.
AB  - Sensory photoreceptors elicit vital physiological adaptations in response to
      incident light. As light-regulated actuators, photoreceptors underpin
      optogenetics, which denotes the noninvasive, reversible, and spatiotemporally
      precise perturbation by light of living cells and organisms. Of particular
      versatility, naturally occurring photoactivated adenylate cyclases promote the
      synthesis of the second messenger cAMP under blue light. Here, we have engineered
      a light-activated phosphodiesterase (LAPD) with complementary light sensitivity
      and catalytic activity by recombining the photosensor module of Deinococcus
      radiodurans bacterial phytochrome with the effector module of Homo sapiens
      phosphodiesterase 2A. Upon red-light absorption, LAPD up-regulates hydrolysis of
      cAMP and cGMP by up to sixfold, whereas far-red light can be used to down
      regulate activity. LAPD also mediates light-activated cAMP and cGMP hydrolysis in
      eukaryotic cell cultures and in zebrafish embryos; crucially, the biliverdin
      chromophore of LAPD is available endogenously and does not need to be provided
      exogenously. LAPD thus establishes a new optogenetic modality that permits light
      control over diverse cAMP/cGMP-mediated physiological processes. Because red
      light penetrates tissue more deeply than light of shorter wavelengths, LAPD
      appears particularly attractive for studies in living organisms. 

PMID- 24889612
TI  - Structural basis for simultaneous recognition of an O-glycan and its attached
      peptide of mucin family by immune receptor PILRalpha.
AB  - Paired Ig-like type 2 receptor alpha (PILRalpha) recognizes a wide range of O
      glycosylated mucin and related proteins to regulate broad immune responses.
      However, the molecular characteristics of these recognitions are largely unknown.
      Here we show that sialylated O-linked sugar T antigen (sTn) and its attached
      peptide region are both required for ligand recognition by PILRalpha.
      Furthermore, we determined the crystal structures of PILRalpha and its complex
      with an sTn and its attached peptide region. The structures show that PILRalpha
      exhibits large conformational change to recognize simultaneously both the sTn O
      glycan and the compact peptide structure constrained by proline residues. Binding
      and functional assays support this binding mode. These findings provide
      significant insight into the binding motif and molecular mechanism (which is
      distinct from sugar-recognition receptors) by which O-glycosylated mucin proteins
      with sTn modifications are recognized in the immune system as well as during
      viral entry. 

PMID- 24889613
TI  - Functional exofacially tagged N-type calcium channels elucidate the interaction
      with auxiliary alpha2delta-1 subunits.
AB  - CaV1 and CaV2 voltage-gated calcium channels are associated with beta and
      alpha2delta accessory subunits. However, examination of cell surface-associated
      CaV2 channels has been hampered by the lack of antibodies to cell surface
      accessible epitopes and of functional exofacially tagged CaV2 channels. Here we
      report the development of fully functional CaV2.2 constructs containing inserted
      surface-accessible exofacial tags, which allow visualization of only those
      channels at the plasma membrane, in both a neuronal cell line and neurons. We
      first examined the effect of the auxiliary subunits. Although alpha2delta
      subunits copurify with CaV2 channels, it has recently been suggested that this
      interaction is easily disrupted and nonquantitative. We have now tested whether
      alpha2delta subunits are associated with these channels at the cell surface. We
      found that, whereas alpha2delta-1 is readily observed at the plasma membrane when
      expressed alone, it appears absent when coexpressed with CaV2.2/beta1b, despite
      our finding that alpha2delta-1 increases plasma-membrane CaV2.2 expression.
      However, this was due to occlusion of the antigenic epitope by association with
      CaV2.2, as revealed by antigen retrieval; thus, our data provide evidence for a
      tight interaction between alpha2delta-1 and the alpha1 subunit at the plasma
      membrane. We further show that, although CaV2.2 cell-surface expression is
      reduced by gabapentin in the presence of wild-type alpha2delta-1 (but not a
      gabapentin-insensitive alpha2delta-1 mutant), the interaction between CaV2.2 and
      alpha2delta-1 is not disrupted by gabapentin. Altogether, these results
      demonstrate that CaV2.2 and alpha2delta-1 are intimately associated at the plasma
      membrane and allow us to infer a region of interaction. 

PMID- 24889614
TI  - Single-particle EM reveals plasticity of interactions between the adenovirus
      penton base and integrin alphaVbeta3.
AB  - Human adenoviruses are double-stranded DNA viruses responsible for numerous
      infections, some of which can be fatal. Furthermore, adenoviruses are currently
      used in clinical trials as vectors for gene therapy applications. Although
      initial binding of adenoviruses to host attachment receptors has been extensively
      characterized, the interactions with the entry receptor (integrins) remain poorly
      understood at the structural level. We characterized the interactions between the
      adenovirus 9 penton base subunit and alphaVbeta3 integrin using fluorescence
      correlation spectroscopy and single-particle electron microscopy to understand
      the mechanisms underlying virus internalization and infection. Our results
      indicate that the penton base subunit can bind integrins with high affinity and
      in several different orientations. These outcomes correlate with the requirement
      of the pentameric penton base to simultaneously bind several integrins to enable
      their clustering and promote virus entry into the host cell. 

PMID- 24889616
TI  - Metabolomics and proteomics reveal impacts of chemically mediated competition on
      marine plankton.
AB  - Competition is a major force structuring marine planktonic communities. The
      release of compounds that inhibit competitors, a process known as allelopathy,
      may play a role in the maintenance of large blooms of the red-tide dinoflagellate
      Karenia brevis, which produces potent neurotoxins that negatively impact coastal
      marine ecosystems. K. brevis is variably allelopathic to multiple competitors,
      typically causing sublethal suppression of growth. We used metabolomic and
      proteomic analyses to investigate the role of chemically mediated ecological
      interactions between K. brevis and two diatom competitors, Asterionellopsis
      glacialis and Thalassiosira pseudonana. The impact of K. brevis allelopathy on
      competitor physiology was reflected in the metabolomes and expressed proteomes of
      both diatoms, although the diatom that co-occurs with K. brevis blooms (A.
      glacialis) exhibited more robust metabolism in response to K. brevis. The
      observed partial resistance of A. glacialis to allelopathy may be a result of its
      frequent exposure to K. brevis blooms in the Gulf of Mexico. For the more
      sensitive diatom, T. pseudonana, which may not have had opportunity to evolve
      resistance to K. brevis, allelopathy disrupted energy metabolism and impeded
      cellular protection mechanisms including altered cell membrane components,
      inhibited osmoregulation, and increased oxidative stress. Allelopathic compounds
      appear to target multiple physiological pathways in sensitive competitors,
      demonstrating that chemical cues in the plankton have the potential to alter
      large-scale ecosystem processes including primary production and nutrient
      cycling. 

PMID- 24889617
TI  - Contact inhibition and high cell density deactivate the mammalian target of
      rapamycin pathway, thus suppressing the senescence program.
AB  - During cell cycle arrest caused by contact inhibition (CI), cells do not undergo
      senescence, thus resuming proliferation after replating. The mechanism of
      senescence avoidance during CI is unknown. Recently, it was demonstrated that the
      senescence program, namely conversion from cell cycle arrest to senescence (i.e.,
      geroconversion), requires mammalian target of rapamycin (mTOR). Geroconversion
      can be suppressed by serum starvation, rapamycin, and hypoxia, which all inhibit
      mTOR. Here we demonstrate that CI, as evidenced by p27 induction in normal cells,
      was associated with inhibition of the mTOR pathway. Furthermore, CI antagonized
      senescence caused by CDK inhibitors. Stimulation of mTOR in contact-inhibited
      cells favored senescence. In cancer cells lacking p27 induction and CI, mTOR was
      still inhibited in confluent culture as a result of conditioning of the medium.
      This inhibition of mTOR suppressed p21-induced senescence. Also, trapping of
      malignant cells among contact-inhibited normal cells antagonized p21-induced
      senescence. Thus, we identified two nonmutually exclusive mechanisms of mTOR
      inhibition in high cell density: (i) CI associated with p27 induction in normal
      cells and (ii) conditioning of the medium, especially in cancer cells. Both
      mechanisms can coincide in various proportions in various cells. Our work
      explains why CI is reversible and, most importantly, why cells avoid senescence
      in vivo, given that cells are contact-inhibited in the organism. 

PMID- 24889618
TI  - Processing multiple visual objects is limited by overlap in neural channels.
AB  - High-level visual categories (e.g., faces, bodies, scenes, and objects) have
      separable neural representations across the visual cortex. Here, we show that
      this division of neural resources affects the ability to simultaneously process
      multiple items. In a behavioral task, we found that performance was superior when
      items were drawn from different categories (e.g., two faces/two scenes) compared
      to when items were drawn from one category (e.g., four faces). The magnitude of
      this mixed-category benefit depended on which stimulus categories were paired
      together (e.g., faces and scenes showed a greater behavioral benefit than objects
      and scenes). Using functional neuroimaging (i.e., functional MRI), we showed that
      the size of the mixed-category benefit was predicted by the amount of separation
      between neural response patterns, particularly within occipitotemporal cortex.
      These results suggest that the ability to process multiple items at once is
      limited by the extent to which those items are represented by separate neural
      populations. 

PMID- 24889619
TI  - Synaptic function of nicastrin in hippocampal neurons.
AB  - Synaptic dysfunction is widely thought to play a key role in the pathogenesis of
      Alzheimer's disease (AD). Presenilins, the major gene products involved in
      familial AD, are essential for short- and long-term synaptic plasticity in mature
      neurons as well as for the survival of cortical neurons during aging. Presenilin
      and nicastrin are both indispensable components of the gamma-secretase complex,
      but it remains unknown whether presenilin regulates synaptic function in a gamma
      secretase-dependent or gamma-secretase-independent manner and whether nicastrin
      plays similar roles in central synapses. In the current study, we address these
      questions using an electrophysiological approach to analyze nicastrin conditional
      knockout (cKO) mice in the hippocampal Schaffer collateral pathway. In these
      mice, we found that, even at 2 mo of age, deletion of nicastrin in excitatory
      neurons of the postnatal forebrain using Cre recombinase expressed under the
      control of the alphaCaMKII promoter led to deficits in presynaptic short-term
      plasticity including paired-pulse facilitation and frequency facilitation.
      Depletion of Ca(2+) in the endoplasmic reticulum mimics and occludes the
      presynaptic facilitation deficits in nicastrin cKO mice, suggesting that
      disrupted intracellular Ca(2+) homeostasis underlies the presynaptic deficits. In
      addition, NMDA receptor-mediated responses and long-term potentiation induced by
      theta-burst stimulation were decreased in nicastrin cKO mice at 3 mo but not at 2
      mo of age. Together, these findings show that, similar to presenilins, nicastrin
      plays essential roles in the regulation of short- and long-term synaptic
      plasticity, highlighting the importance of gamma-secretase in the function of
      mature synapses. 

PMID- 24889620
TI  - Female hurricanes are deadlier than male hurricanes.
AB  - Do people judge hurricane risks in the context of gender-based expectations? We
      use more than six decades of death rates from US hurricanes to show that feminine
      named hurricanes cause significantly more deaths than do masculine-named
      hurricanes. Laboratory experiments indicate that this is because hurricane names
      lead to gender-based expectations about severity and this, in turn, guides
      respondents' preparedness to take protective action. This finding indicates an
      unfortunate and unintended consequence of the gendered naming of hurricanes, with
      important implications for policymakers, media practitioners, and the general
      public concerning hurricane communication and preparedness. 

PMID- 24889622
TI  - Differential targeting of VDAC3 mRNA isoforms influences mitochondria morphology.
AB  - Intracellular targeting of mRNAs has recently emerged as a prevalent mechanism to
      control protein localization. For mitochondria, a cotranslational model of
      protein import is now proposed in parallel to the conventional posttranslational
      model, and mitochondrial targeting of mRNAs has been demonstrated in various
      organisms. Voltage-dependent anion channels (VDACs) are the most abundant
      proteins in the outer mitochondrial membrane and the major transport pathway for
      numerous metabolites. Four nucleus-encoded VDACs have been identified in
      Arabidopsis thaliana. Alternative cleavage and polyadenylation generate two VDAC3
      mRNA isoforms differing by their 3' UTR. By using quantitative RT-PCR and in vivo
      mRNA visualization approaches, the two mRNA variants were shown differentially
      associated with mitochondria. The longest mRNA presents a 3' extension named
      alternative UTR (aUTR) that is necessary and sufficient to target VDAC3 mRNA to
      the mitochondrial surface. Moreover, aUTR is sufficient for the mitochondrial
      targeting of a reporter transcript, and can be used as a tool to target an
      unrelated mRNA to the mitochondrial surface. Finally, VDAC3-aUTR mRNA variant
      impacts mitochondria morphology and size, demonstrating the role of mRNA
      targeting in mitochondria biogenesis. 

PMID- 24889621
TI  - Single-cell nucleosome mapping reveals the molecular basis of gene expression
      heterogeneity.
AB  - Nucleosomes, the basic unit of chromatin, have a critical role in the control of
      gene expression. Nucleosome positions have generally been determined by examining
      bulk populations of cells and then correlated with overall gene expression. Here,
      we describe a technique to determine nucleosome positioning in single cells by
      virtue of the ability of the nucleosome to protect DNA from GpC methylation. In
      the acid phosphatase inducible PHO5 gene, we find that there is significant cell
      to-cell variation in nucleosome positions and shifts in nucleosome positioning
      correlate with changes in gene expression. However, nucleosome positioning is not
      absolute, and even with major shifts in gene expression, some cells fail to
      change nucleosome configuration. Mutations of the PHO5 promoter that introduce a
      poly(dA:dT) tract-stimulated gene expression under nonpermissive conditions led
      to shifts of positioned nucleosomes similar to induction of PHO5. By contrast,
      mutations that altered AA/TT/AT periodicity reduced gene expression upon PHO5
      induction and stabilized nucleosomes in most cells, suggesting that enhanced
      nucleosome affinity for DNA antagonizes chromatin remodelers. Finally, we
      determined nucleosome positioning in two regions described as "fuzzy" or
      nucleosome-free when examined in a bulk assay. These regions consisted of
      distinct nucleosomes with a larger footprint for potential location and an
      increase population of cells lacking a nucleosome altogether. These data indicate
      an underlying complexity of nucleosome positioning that may contribute to the
      flexibility and heterogeneity of gene expression. 

PMID- 24889623
TI  - A spatially nonselective baseline signal in parietal cortex reflects the
      probability of a monkey's success on the current trial.
AB  - We recorded the activity of neurons in the lateral intraparietal area of two
      monkeys while they performed two similar visual search tasks, one difficult, one
      easy. Each task began with a period of fixation followed by an array consisting
      of a single capital T and a number of lowercase t's. The monkey had to find the
      capital T and report its orientation, upright or inverted, with a hand movement.
      In the easy task the monkey could explore the array with saccades. In the
      difficult task the monkey had to continue fixating and find the capital T in the
      visual periphery. The baseline activity measured during the fixation period, at a
      time in which the monkey could not know if the impending task would be difficult
      or easy or where the target would appear, predicted the monkey's probability of
      success or failure on the task. The baseline activity correlated inversely with
      the monkey's recent history of success and directly with the intensity of the
      response to the search array on the current trial. The baseline activity was
      unrelated to the monkey's spatial locus of attention as determined by the
      location of the cue in a cued visual reaction time task. We suggest that rather
      than merely reflecting the noise in the system, the baseline signal reflects the
      cortical manifestation of modulatory state, motivational, or arousal pathways,
      which determine the efficiency of cortical sensorimotor processing and the
      quality of the monkey's performance. 

PMID- 24889615
TI  - The Irish potato famine pathogen Phytophthora infestans originated in central
      Mexico rather than the Andes.
AB  - Phytophthora infestans is a destructive plant pathogen best known for causing the
      disease that triggered the Irish potato famine and remains the most costly potato
      pathogen to manage worldwide. Identification of P. infestan's elusive center of
      origin is critical to understanding the mechanisms of repeated global emergence
      of this pathogen. There are two competing theories, placing the origin in either
      South America or in central Mexico, both of which are centers of diversity of
      Solanum host plants. To test these competing hypotheses, we conducted detailed
      phylogeographic and approximate Bayesian computation analyses, which are suitable
      approaches to unraveling complex demographic histories. Our analyses used
      microsatellite markers and sequences of four nuclear genes sampled from
      populations in the Andes, Mexico, and elsewhere. To infer the ancestral state, we
      included the closest known relatives Phytophthora phaseoli, Phytophthora
      mirabilis, and Phytophthora ipomoeae, as well as the interspecific hybrid
      Phytophthora andina. We did not find support for an Andean origin of P.
      infestans; rather, the sequence data suggest a Mexican origin. Our findings
      support the hypothesis that populations found in the Andes are descendants of the
      Mexican populations and reconcile previous findings of ancestral variation in the
      Andes. Although centers of origin are well documented as centers of evolution and
      diversity for numerous crop plants, the number of plant pathogens with a known
      geographic origin are limited. This work has important implications for our
      understanding of the coevolution of hosts and pathogens, as well as the
      harnessing of plant disease resistance to manage late blight. 

PMID- 24889624
TI  - Antarctic sea ice control on ocean circulation in present and glacial climates.
AB  - In the modern climate, the ocean below 2 km is mainly filled by waters sinking
      into the abyss around Antarctica and in the North Atlantic. Paleoproxies indicate
      that waters of North Atlantic origin were instead absent below 2 km at the Last
      Glacial Maximum, resulting in an expansion of the volume occupied by Antarctic
      origin waters. In this study we show that this rearrangement of deep water masses
      is dynamically linked to the expansion of summer sea ice around Antarctica. A
      simple theory further suggests that these deep waters only came to the surface
      under sea ice, which insulated them from atmospheric forcing, and were weakly
      mixed with overlying waters, thus being able to store carbon for long times. This
      unappreciated link between the expansion of sea ice and the appearance of a
      voluminous and insulated water mass may help quantify the ocean's role in
      regulating atmospheric carbon dioxide on glacial-interglacial timescales.
      Previous studies pointed to many independent changes in ocean physics to account
      for the observed swings in atmospheric carbon dioxide. Here it is shown that many
      of these changes are dynamically linked and therefore must co-occur. 

PMID- 24889625
TI  - Direct conversion of plant biomass to ethanol by engineered Caldicellulosiruptor
      bescii.
AB  - Ethanol is the most widely used renewable transportation biofuel in the United
      States, with the production of 13.3 billion gallons in 2012 [John UM (2013)
      Contribution of the Ethanol Industry to the Economy of the United States].
      Despite considerable effort to produce fuels from lignocellulosic biomass,
      chemical pretreatment and the addition of saccharolytic enzymes before microbial
      bioconversion remain economic barriers to industrial deployment [Lynd LR, et al.
      (2008) Nat Biotechnol 26(2):169-172]. We began with the thermophilic, anaerobic,
      cellulolytic bacterium Caldicellulosiruptor bescii, which efficiently uses
      unpretreated biomass, and engineered it to produce ethanol. Here we report the
      direct conversion of switchgrass, a nonfood, renewable feedstock, to ethanol
      without conventional pretreatment of the biomass. This process was accomplished
      by deletion of lactate dehydrogenase and heterologous expression of a Clostridium
      thermocellum bifunctional acetaldehyde/alcohol dehydrogenase. Whereas wild-type
      C. bescii lacks the ability to make ethanol, 70% of the fermentation products in
      the engineered strain were ethanol [12.8 mM ethanol directly from 2% (wt/vol)
      switchgrass, a real-world substrate] with decreased production of acetate by 38%
      compared with wild-type. Direct conversion of biomass to ethanol represents a new
      paradigm for consolidated bioprocessing, offering the potential for carbon
      neutral, cost-effective, sustainable fuel production. 

PMID- 24889627
TI  - Pressure-enabled phonon engineering in metals.
AB  - We present a combined first-principles and experimental study of the electrical
      resistivity in aluminum and copper samples under pressures up to 2 GPa. The
      calculations are based on first-principles density functional perturbation
      theory, whereas the experimental setup uses a solid media piston-cylinder
      apparatus at room temperature. We find that upon pressurizing each metal, the
      phonon spectra are blue-shifted and the net electron-phonon interaction is
      suppressed relative to the unstrained crystal. This reduction in electron-phonon
      scattering results in a decrease in the electrical resistivity under pressure,
      which is more pronounced for aluminum than for copper. We show that density
      functional perturbation theory can be used to accurately predict the pressure
      response of the electrical resistivity in these metals. This work demonstrates
      how the phonon spectra in metals can be engineered through pressure to achieve
      more attractive electrical properties. 

PMID- 24889626
TI  - Type I interferon is a therapeutic target for virus-induced lethal vascular
      damage.
AB  - The outcome of a viral infection reflects the balance between virus virulence and
      host susceptibility. The clone 13 (Cl13) variant of lymphocytic choriomeningitis
      virus--a prototype of Old World arenaviruses closely related to Lassa fever virus
      -elicits in C57BL/6 and BALB/c mice abundant negative immunoregulatory molecules,
      associated with T-cell exhaustion, negligible T-cell-mediated injury, and high
      virus titers that persist. Conversely, here we report that in NZB mice, despite
      the efficient induction of immunoregulatory molecules and high viremia, Cl13
      generated a robust cytotoxic T-cell response, resulting in thrombocytopenia,
      pulmonary endothelial cell loss, vascular leakage, and death within 6-8 d. These
      pathogenic events required type I IFN (IFN-I) signaling on nonhematopoietic cells
      and were completely abrogated by IFN-I receptor blockade. Thus, IFN-I may play a
      prominent role in hemorrhagic fevers and other acute virus infections associated
      with severe vascular pathology, and targeting IFN-I or downstream effector
      molecules may be an effective therapeutic approach.

PMID- 24889628
TI  - Measuring hydrogen exchange rates in invisible protein excited states.
AB  - Hydrogen exchange rates have become a valuable probe for studying the
      relationship between dynamics and structure and for dissecting the mechanism by
      which proteins fold to their native conformation. Typically measured rates
      correspond to averages over all protein states from which hydrogen exchange can
      occur. Here we describe a new NMR experiment based on chemical exchange
      saturation transfer that provides an avenue for obtaining uncontaminated, per
      residue amide hydrogen exchange rates for interconverting native and invisible
      states so long as they can be separated on the basis of distinct (15)N chemical
      shifts. The approach is applied to the folding reaction of the Fyn SH3 domain
      that exchanges between a highly populated, NMR-visible native state and a
      conformationally excited, NMR-invisible state, corresponding to the unfolded
      ensemble. Excellent agreement between experimentally derived hydrogen exchange
      rates of the excited state at a pair of pHs is obtained, taking into account the
      expected dependence of exchange on pH. Extracted rates for the unfolded ensemble
      have been used to test hydrogen exchange predictions based on the primary protein
      sequence that are used in many analyses of solvent exchange rates, with a Pearson
      correlation coefficient of 0.84 obtained. 

PMID- 24889629
TI  - Protons are a neurotransmitter that regulates synaptic plasticity in the lateral
      amygdala.
AB  - Stimulating presynaptic terminals can increase the proton concentration in
      synapses. Potential receptors for protons are acid-sensing ion channels (ASICs),
      Na(+)- and Ca(2+)-permeable channels that are activated by extracellular
      acidosis. Those observations suggest that protons might be a neurotransmitter. We
      found that presynaptic stimulation transiently reduced extracellular pH in the
      amygdala. The protons activated ASICs in lateral amygdala pyramidal neurons,
      generating excitatory postsynaptic currents. Moreover, both protons and ASICs
      were required for synaptic plasticity in lateral amygdala neurons. The results
      identify protons as a neurotransmitter, and they establish ASICs as the
      postsynaptic receptor. They also indicate that protons and ASICs are a
      neurotransmitter/receptor pair critical for amygdala-dependent learning and
      memory. 

PMID- 24889631
TI  - Pruning of memories by context-based prediction error.
AB  - The capacity of long-term memory is thought to be virtually unlimited. However,
      our memory bank may need to be pruned regularly to ensure that the information
      most important for behavior can be stored and accessed efficiently. Using
      functional magnetic resonance imaging of the human brain, we report the discovery
      of a context-based mechanism for determining which memories to prune.
      Specifically, when a previously experienced context is reencountered, the brain
      automatically generates predictions about which items should appear in that
      context. If an item fails to appear when strongly expected, its representation in
      memory is weakened, and it is more likely to be forgotten. We find robust support
      for this mechanism using multivariate pattern classification and pattern
      similarity analyses. The results are explained by a model in which context-based
      predictions activate item representations just enough for them to be weakened
      during a misprediction. These findings reveal an ongoing and adaptive process for
      pruning unreliable memories. 

PMID- 24889632
TI  - Deep mantle structure as a reference frame for movements in and on the Earth.
AB  - Earth's residual geoid is dominated by a degree-2 mode, with elevated regions
      above large low shear-wave velocity provinces on the core-mantle boundary beneath
      Africa and the Pacific. The edges of these deep mantle bodies, when projected
      radially to the Earth's surface, correlate with the reconstructed positions of
      large igneous provinces and kimberlites since Pangea formed about 320 million
      years ago. Using this surface-to-core-mantle boundary correlation to locate
      continents in longitude and a novel iterative approach for defining a
      paleomagnetic reference frame corrected for true polar wander, we have developed
      a model for absolute plate motion back to earliest Paleozoic time (540 Ma). For
      the Paleozoic, we have identified six phases of slow, oscillatory true polar
      wander during which the Earth's axis of minimum moment of inertia was similar to
      that of Mesozoic times. The rates of Paleozoic true polar wander (<1 degrees /My)
      are compatible with those in the Mesozoic, but absolute plate velocities are, on
      average, twice as high. Our reconstructions generate geologically plausible
      scenarios, with large igneous provinces and kimberlites sourced from the margins
      of the large low shear-wave velocity provinces, as in Mesozoic and Cenozoic
      times. This absolute kinematic model suggests that a degree-2 convection mode
      within the Earth's mantle may have operated throughout the entire Phanerozoic. 

PMID- 24889630
TI  - Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with
      congenital lipodystrophy and fatty liver disease.
AB  - Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and
      is an essential component in all cellular membranes. The biochemistry of de novo
      PC synthesis by the Kennedy pathway is well established, but less is known about
      the physiological functions of PC. We identified two unrelated patients with
      defects in the Kennedy pathway due to biallellic loss-of-function mutations in
      phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this
      pathway. The mutations lead to a marked reduction in PCYT1A expression and PC
      synthesis. The phenotypic consequences include some features, such as severe
      fatty liver and low HDL cholesterol levels, that are predicted by the results of
      previously reported liver-specific deletion of murine Pcyt1a. Both patients also
      had lipodystrophy, severe insulin resistance, and diabetes, providing evidence
      for an additional and essential role for PCYT1A-generated PC in the normal
      function of white adipose tissue and insulin action. 

PMID- 24889633
TI  - Way-finding in displaced clock-shifted bees proves bees use a cognitive map.
AB  - Mammals navigate by means of a metric cognitive map. Insects, most notably bees
      and ants, are also impressive navigators. The question whether they, too, have a
      metric cognitive map is important to cognitive science and neuroscience.
      Experimentally captured and displaced bees often depart from the release site in
      the compass direction they were bent on before their capture, even though this no
      longer heads them toward their goal. When they discover their error, however, the
      bees set off more or less directly toward their goal. This ability to orient
      toward a goal from an arbitrary point in the familiar environment is evidence
      that they have an integrated metric map of the experienced environment. We report
      a test of an alternative hypothesis, which is that all the bees have in memory is
      a collection of snapshots that enable them to recognize different landmarks and,
      associated with each such snapshot, a sun-compass-referenced home vector derived
      from dead reckoning done before and after previous visits to the landmark. We
      show that a large shift in the sun-compass rapidly induced by general anesthesia
      does not alter the accuracy or speed of the homeward-oriented flight made after
      the bees discover the error in their initial postrelease flight. This result
      rules out the sun-referenced home-vector hypothesis, further strengthening the
      now extensive evidence for a metric cognitive map in bees. 

PMID- 24889634
TI  - Water-mediated ion-ion interactions are enhanced at the water vapor-liquid
      interface.
AB  - There is overwhelming evidence that ions are present near the vapor-liquid
      interface of aqueous salt solutions. Charged groups can also be driven to
      interfaces by attaching them to hydrophobic moieties. Despite their importance in
      many self-assembly phenomena, how ion-ion interactions are affected by interfaces
      is not understood. We use molecular simulations to show that the effective forces
      between small ions change character dramatically near the water vapor-liquid
      interface. Specifically, the water-mediated attraction between oppositely charged
      ions is enhanced relative to that in bulk water. Further, the repulsion between
      like-charged ions is weaker than that expected from a continuum dielectric
      description and can even become attractive as the ions are drawn to the vapor
      side. We show that thermodynamics of ion association are governed by a delicate
      balance of ion hydration, interfacial tension, and restriction of capillary
      fluctuations at the interface, leading to nonintuitive phenomena, such as water
      mediated like charge attraction. "Sticky" electrostatic interactions may have
      important consequences on biomolecular structure, assembly, and aggregation at
      soft liquid interfaces. We demonstrate this by studying an interfacially active
      model peptide that changes its structure from alpha-helical to a hairpin-turn
      like one in response to charging of its ends. 

PMID- 24889635
TI  - Pathway for Mn-cluster oxidation by tyrosine-Z in the S2 state of photosystem II.
AB  - Water oxidation in photosynthetic organisms occurs through the five intermediate
      steps S0-S4 of the Kok cycle in the oxygen evolving complex of photosystem II
      (PSII). Along the catalytic cycle, four electrons are subsequently removed from
      the Mn4CaO5 core by the nearby tyrosine Tyr-Z, which is in turn oxidized by the
      chlorophyll special pair P680, the photo-induced primary donor in PSII. Recently,
      two Mn4CaO5 conformations, consistent with the S2 state (namely, S2(A) and S2(B)
      models) were suggested to exist, perhaps playing a different role within the S2
      to-S3 transition. Here we report multiscale ab initio density functional theory
      plus U simulations revealing that upon such oxidation the relative thermodynamic
      stability of the two previously proposed geometries is reversed, the S2(B) state
      becoming the leading conformation. In this latter state a proton coupled electron
      transfer is spontaneously observed at ~100 fs at room temperature dynamics. Upon
      oxidation, the Mn cluster, which is tightly electronically coupled along dynamics
      to the Tyr-Z tyrosyl group, releases a proton from the nearby W1 water molecule
      to the close Asp-61 on the femtosecond timescale, thus undergoing a
      conformational transition increasing the available space for the subsequent
      coordination of an additional water molecule. The results can help to rationalize
      previous spectroscopic experiments and confirm, for the first time to our
      knowledge, that the water-splitting reaction has to proceed through the S2(B)
      conformation, providing the basis for a structural model of the S3 state.

PMID- 24889636
TI  - Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2.
AB  - The antiglycemic drug metformin, widely prescribed as first-line treatment of
      type II diabetes mellitus, has lifespan-extending properties. Precisely how this
      is achieved remains unclear. Via a quantitative proteomics approach using the
      model organism Caenorhabditis elegans, we gained molecular understanding of the
      physiological changes elicited by metformin exposure, including changes in
      branched-chain amino acid catabolism and cuticle maintenance. We show that
      metformin extends lifespan through the process of mitohormesis and propose a
      signaling cascade in which metformin-induced production of reactive oxygen
      species increases overall life expectancy. We further address an important issue
      in aging research, wherein so far, the key molecular link that translates the
      reactive oxygen species signal into a prolongevity cue remained elusive. We show
      that this beneficial signal of the mitohormetic pathway is propagated by the
      peroxiredoxin PRDX-2. Because of its evolutionary conservation, peroxiredoxin
      signaling might underlie a general principle of prolongevity signaling. 

PMID- 24889638
TI  - Reconstitution of the mitochondrial calcium uniporter in yeast.
AB  - The mitochondrial calcium uniporter is a highly selective calcium channel
      distributed broadly across eukaryotes but absent in the yeast Saccharomyces
      cerevisiae. The molecular components of the human uniporter holocomplex (uniplex)
      have been identified recently. The uniplex consists of three membrane-spanning
      subunits--mitochondrial calcium uniporter (MCU), its paralog MCUb, and essential
      MCU regulator (EMRE)--and two soluble regulatory components--MICU1 and its
      paralog MICU2. The minimal components sufficient for in vivo uniporter activity
      are unknown. Here we consider Dictyostelium discoideum (Dd), a member of the
      Amoebazoa outgroup of Metazoa and Fungi, and show that it has a highly simplified
      uniporter machinery. We show that D. discoideum mitochondria exhibit membrane
      potential-dependent calcium uptake compatible with uniporter activity, and also
      that expression of DdMCU complements the mitochondrial calcium uptake defect in
      human cells lacking MCU or EMRE. Moreover, expression of DdMCU in yeast alone is
      sufficient to reconstitute mitochondrial calcium uniporter activity. Having
      established yeast as an in vivo reconstitution system, we then reconstituted the
      human uniporter. We show that coexpression of MCU and EMRE is sufficient for
      uniporter activity, whereas expression of MCU alone is insufficient. Our work
      establishes yeast as a powerful in vivo reconstitution system for the uniporter.
      Using this system, we confirm that MCU is the pore-forming subunit, define the
      minimal genetic elements sufficient for metazoan and nonmetazoan uniporter
      activity, and provide valuable insight into the evolution of the uniporter
      machinery.

PMID- 24889640
TI  - Slow slip and the transition from fast to slow fronts in the rupture of
      frictional interfaces.
AB  - The failure of the population of microjunctions forming the frictional interface
      between two solids is central to fields ranging from biomechanics to seismology.
      This failure is mediated by the propagation along the interface of various types
      of rupture fronts, covering a wide range of velocities. Among them are the so
      called slow fronts, which are recently discovered fronts much slower than the
      materials' sound speeds. Despite intense modeling activity, the mechanisms
      underlying slow fronts remain elusive. Here, we introduce a multiscale model
      capable of reproducing both the transition from fast to slow fronts in a single
      rupture event and the short-time slip dynamics observed in recent experiments. We
      identify slow slip immediately following the arrest of a fast front as a
      phenomenon sufficient for the front to propagate further at a much slower pace.
      Whether slow fronts are actually observed is controlled both by the interfacial
      stresses and by the width of the local distribution of forces among
      microjunctions. Our results show that slow fronts are qualitatively different
      from faster fronts. Because the transition from fast to slow fronts is
      potentially as generic as slow slip, we anticipate that it might occur in the
      wide range of systems in which slow slip has been reported, including seismic
      faults. 

PMID- 24889637
TI  - Spectroscopic and computational insight into the activation of O2 by the
      mononuclear Cu center in polysaccharide monooxygenases.
AB  - Strategies for O2 activation by copper enzymes were recently expanded to include
      mononuclear Cu sites, with the discovery of the copper-dependent polysaccharide
      monooxygenases, also classified as auxiliary-activity enzymes 9-11 (AA9-11).
      These enzymes are finding considerable use in industrial biofuel production.
      Crystal structures of polysaccharide monooxygenases have emerged, but
      experimental studies are yet to determine the solution structure of the Cu site
      and how this relates to reactivity. From X-ray absorption near edge structure and
      extended X-ray absorption fine structure spectroscopies, we observed a change
      from four-coordinate Cu(II) to three-coordinate Cu(I) of the active site in
      solution, where three protein-derived nitrogen ligands coordinate the Cu in both
      redox states, and a labile hydroxide ligand is lost upon reduction. The
      spectroscopic data allowed for density functional theory calculations of an
      enzyme active site model, where the optimized Cu(I) and (II) structures were
      consistent with the experimental data. The O2 reactivity of the Cu(I) site was
      probed by EPR and stopped-flow absorption spectroscopies, and a rapid one
      electron reduction of O2 and regeneration of the resting Cu(II) enzyme were
      observed. This reactivity was evaluated computationally, and by calibration to Cu
      superoxide model complexes, formation of an end-on Cu-AA9-superoxide species was
      found to be thermodynamically favored. We discuss how this thermodynamically
      difficult one-electron reduction of O2 is enabled by the unique protein structure
      where two nitrogen ligands from His1 dictate formation of a T-shaped Cu(I) site,
      which provides an open coordination position for strong O2 binding with very
      little reorganization energy. 

PMID- 24889641
TI  - Transcription is initiated on silent variant surface glycoprotein expression
      sites despite monoallelic expression in Trypanosoma brucei.
AB  - African trypanosomes survive the immune defense of their hosts by regularly
      changing their antigenic coat made of variant surface glycoprotein (VSG). The
      Trypanosoma brucei genome contains more than 1,000 VSG genes. To be expressed, a
      given VSG gene must be located in one of 15 telomeric regions termed "VSG
      expression sites" (ESs), each of which contains a polycistronic transcription
      unit that includes ES-associated genes. Only one ES is fully active at a time, so
      only one VSG gene is transcribed per cell. Although this monoallelic expression
      is controlled at the transcriptional level, the precise molecular mechanism for
      this control is not understood. Here we report that in single cells transcription
      is initiated on several ESs simultaneously, indicating that the monoallelic
      control is not determined only at transcription initiation, but also at further
      control steps such as transcription elongation or RNA processing. 

PMID- 24889642
TI  - Coupled counterrotating polariton condensates in optically defined annular
      potentials.
AB  - Polariton condensates are macroscopic quantum states formed by half-matter half
      light quasiparticles, thus connecting the phenomena of atomic Bose-Einstein
      condensation, superfluidity, and photon lasing. Here we report the spontaneous
      formation of such condensates in programmable potential landscapes generated by
      two concentric circles of light. The imposed geometry supports the emergence of
      annular states that extend up to 100 MUm, yet are fully coherent and exhibit a
      spatial structure that remains stable for minutes at a time. These states exhibit
      a petal-like intensity distribution arising due to the interaction of two
      superfluids counterpropagating in the circular waveguide defined by the optical
      potential. In stark contrast to annular modes in conventional lasing systems, the
      resulting standing wave patterns exhibit only minimal overlap with the pump laser
      itself. We theoretically describe the system using a complex Ginzburg-Landau
      equation, which indicates why the condensate wants to rotate. Experimentally, we
      demonstrate the ability to precisely control the structure of the petal
      condensates both by carefully modifying the excitation geometry as well as
      perturbing the system on ultrafast timescales to reveal unexpected superfluid
      dynamics. 

PMID- 24889643
TI  - Steeper declines in forest photosynthesis than respiration explain age-driven
      decreases in forest growth.
AB  - The traditional view of forest dynamics originated by Kira and Shidei [Kira T,
      Shidei T (1967) Jap J Ecol 17:70-87] and Odum [Odum EP (1969) Science
      164(3877):262-270] suggests a decline in net primary productivity (NPP) in aging
      forests due to stabilized gross primary productivity (GPP) and continuously
      increased autotrophic respiration (Ra). The validity of these trends in GPP and
      Ra is, however, very difficult to test because of the lack of long-term ecosystem
      scale field observations of both GPP and Ra. Ryan and colleagues [Ryan MG,
      Binkley D, Fownes JH (1997) Ad Ecol Res 27:213-262] have proposed an alternative
      hypothesis drawn from site-specific results that aboveground respiration and
      belowground allocation decreased in aging forests. Here, we analyzed data from a
      recently assembled global database of carbon fluxes and show that the classical
      view of the mechanisms underlying the age-driven decline in forest NPP is
      incorrect and thus support Ryan's alternative hypothesis. Our results
      substantiate the age-driven decline in NPP, but in contrast to the traditional
      view, both GPP and Ra decline in aging boreal and temperate forests. We find that
      the decline in NPP in aging forests is primarily driven by GPP, which decreases
      more rapidly with increasing age than Ra does, but the ratio of NPP/GPP remains
      approximately constant within a biome. Our analytical models describing forest
      succession suggest that dynamic forest ecosystem models that follow the
      traditional paradigm need to be revisited. 

PMID- 24889644
TI  - Anti-HIV drug particles may overcome lymphatic drug insufficiency and associated
      HIV persistence.

PMID- 24889645
TI  - Carefully thinking about telomeres.

PMID- 24889646
TI  - Phonological awareness and reading in boys with fragile X syndrome.
AB  - BACKGROUND: Reading delays are well documented in children with fragile X
      syndrome (FXS), but few studies have examined linguistic precursors of reading in
      this population. This study examined the longitudinal development of phonological
      awareness and its relationship with basic reading in boys with FXS. Individual
      differences in genetic, social-behavioral and environmental factors were also
      investigated as predictors of phonological awareness. METHODS: Participants
      included 54 boys with FXS and 53 typically developing (TD) mental age-matched
      peers who completed assessments of phonological awareness, nonverbal
      intelligence, and reading annually for up to 4 years. FMRP level and autism
      symptomatology were also measured within the FXS group. Hierarchical linear
      modeling was used to examine change in phonological awareness over time and its
      predictors. Linear regression was used to examine phonological awareness as a
      predictor of word reading. RESULTS: Boys with FXS exhibited slower growth than TD
      peers in phonological awareness only when nonverbal cognitive abilities were not
      controlled. The rate of change in phonological awareness decreased significantly
      after age 10 in boys with FXS. Phonological awareness accounted for 18% unique
      variance in basic reading ability after controlling for nonverbal cognition, with
      similar relationships across groups. CONCLUSION: Phonological awareness skills in
      the boys with FXS were commensurate with their nonverbal cognitive abilities,
      with similar relationships between phonological awareness and reading as observed
      in the TD mental age-matched peers. More research is needed to examine potential
      causal relationships between phonological awareness, other language skills, and
      reading abilities in individuals with FXS and other neurodevelopmental disorders.

PMID- 24889647
TI  - Aesthetic recovery of alveolar atrophy following autogenous onlay bone grafting
      using interconnected porous hydroxyapatite ceramics (IP-CHA) and resorbable poly
      L-lactic/polyglycolic acid screws: case report.
AB  - BACKGROUND: Onlay bone grafting techniques have some problems related to the
      limited volume of autogenous grafted bone and need for surgery to remove bone
      fixing screws. Here, we report a case of horizontal alveolar ridge atrophy
      following resection of a maxillary bone cyst, in which autogenous onlay bone
      grafting with interconnected porous hydroxyapatite ceramics (IP-CHA) and
      bioresorbable poly-L-lactic/polyglycolic acid (PLLA-PGA) screws was utilized.
      CASE PRESENTATION: A 51-year-old man had aesthetic complications related to
      alveolar atrophy following maxillary bone cyst extraction. We performed onlay
      grafting for aesthetic alveolar bone recovery using IP-CHA to provide adequate
      horizontal bone volume and PLLA-PGA screws for bone fixing to avoid later damage
      to host bone during surgical removal. During the operation, an autogenous
      cortical bone block was collected from the ramus mandibular and fixed to the
      alveolar ridge with PLLA-PGA screws, then the gap between the bone block and
      recipient bone was filled with a granular type of IP-CHA. Post-surgery
      orthopantomograph and CT scan findings showed no abnormal resorption of the
      grafted bone, and increased radiopacity, which indicated new bone formation in
      the area implanted with IP-CHA. CONCLUSION: Our results show that IP-CHA and
      resorbable PLLA-PGA screws are useful materials for autogenous onlay bone
      grafting.

PMID- 24889649
TI  - Eight novel F13A1 gene missense mutations in patients with mild FXIII deficiency:
      in silico analysis suggests changes in FXIII-A subunit structure/function.
AB  - Mild FXIII deficiency is an under-diagnosed disorder because the carriers of this
      deficiency are often asymptomatic and reveal a phenotype only under special
      circumstances like surgery or induced trauma. Mutational reports from this type
      of deficiency have been rare. In this study, we present the phenotypic and
      genotypic data of nine patients showing mild FXIII-A deficiency caused by eight
      novel heterozygous missense mutations (Pro166Leu, Arg171Gln, His342Tyr,
      Gln415Arg, Leu529Pro, Gln601Lys, Arg703Gln and Arg715Gly) in the F13A1 gene. None
      of these variants were seen in 200 healthy controls. In silico structural
      analysis of the local wild-type protein structures (activated and non-activated)
      from X-ray crystallographic models downloaded from the protein databank
      identified potential structural/functional effects for the identified mutations.
      The missense mutations in the core domain are suggested to be directly
      influencing the catalytic triad. Mutations on other domains might influence other
      critical factors such as activation peptide cleavage or the barrel domain
      integrity. In vitro expression and subsequent biochemical studies in the future
      will be able to confirm the pathophysiological mechanisms proposed for the
      mutations in this article. 

PMID- 24889650
TI  - Displacement of Dental Implants Into the Maxillary Sinus: A Retrospective Study
      of Twenty-One Patients.
AB  - BACKGROUND: One possible complication of implant surgery in the posterior maxilla
      is the displacement of implants into the maxillary sinus. PURPOSE: To report on
      clinical and radiological findings and on biological, surgical, and biomechanical
      considerations in cases of implant displacement. MATERIALS AND METHODS: This is a
      retrospective study of 21 patients referred to the Department of Head and Neck
      Surgery, Second University of Naples, due to implants displaced into the
      maxillary sinus. Patient, implant, and treatment data were collected, and 1-year
      follow-up was made. RESULTS: A total of 24 displaced implants were diagnosed and
      surgically removed through an antrostomy in the lateral sinus wall. Implant
      displacement occurred after functional loading in only one case; in the remaining
      cases, displacement occurred either perioperatively or postoperatively prior to
      loading. Besides the displacement, eight patients suffered from maxillary
      sinusitis, treated with a Caldwell-Luc operation. Healing was uneventful for all
      patients, and no sinusitis relapse or late postoperative complication was present
      at 1-year follow-up. CONCLUSIONS: It is reasonable to affirm that the major cause
      of displacement of implants is related, most of the time, to incorrect treatment
      planning and/or a poorly performed surgical procedure. When implant displacement
      occurs, the displaced foreign body has to be removed in order to avoid sinus
      pathology.

PMID- 24889648
TI  - Divergent mucosal and systemic responses in children in response to acute otitis
      media.
AB  - Acute otitis media (AOM), induced by respiratory bacteria, is a significant cause
      of children seeking medical attention worldwide. Some children are highly prone
      to AOMs, suffering three to four recurrent infections per year (prone). We
      previously determined that this population of children could have diminished anti
      bacterial immune responses in peripheral blood that could fail to limit bacterial
      colonization in the nasopharynx (NP). Here, we examined local NP and middle ear
      (ME) responses and compared them to peripheral blood to examine whether the
      mucosa responses were similar to the peripheral blood responses. Moreover, we
      examined differences in effector cytokine responses between these two populations
      in the NP, ME and blood compartments at the onset of an AOM caused by either
      Streptococcus pneumoniae or non-typeable Haemophilus influenzae. We found that
      plasma effector cytokines patterned antigen-recall responses of CD4 T cells, with
      lower responses detected in prone children. ME cytokine levels did not mirror
      blood, but were more similar to the NP. Interferon (IFN)-gamma and interleukin
      (IL)-17 in the NP were similar in prone and non-prone children, while IL-2
      production was higher in prone children. The immune responses diverged in the
      mucosal and blood compartments at the onset of a bacterial ME infection, thus
      highlighting differences between local and systemic immune responses that could
      co-ordinate anti-bacterial immune responses in young children.

PMID- 24889651
TI  - Transitioning of special needs paediatric patients to adult special needs dental
      services.
AB  - BACKGROUND: Special needs dentistry is in its infancy compared to other dental
      specialties. Continuity of care through transition from paediatric to adult
      dental care providers is unknown. This study seeks to determine the nature of
      transition practices adopted by paediatric and special needs (SN) specialists
      practising throughout Australia. METHODS: A survey was sent to all paediatric and
      SN specialist dentists in Australia to determine the nature of current transition
      practices for paediatric SN patients in Australia. Two subsequent mail-outs were
      sent to non-responders. RESULTS: Forty-nine specialist dentists registered across
      Australia completed the survey, of which 35 (71%) were paediatric dentists and 14
      (29%) were SN dentists. Both paediatric and SN dentists treated patients over the
      age of 18. Of the total paediatric dentists who had transition discussions with
      their paediatric patients and their families, the majority (over 80%) discussed
      treatment options available as part of future oral care management. Paediatric
      dentists identified level of independence and financial situations as the most
      significant barrier for transition. CONCLUSIONS: Key factors exist that should be
      discussed with SN patients and their parents and/or guardians in order to enhance
      the prospect of sustained dental care into adulthood.

PMID- 24889652
TI  - Gene profiling reveals association between altered Wnt signaling and loss of T
      cell potential with age in human hematopoietic stem cells.
AB  - Functional decline of the hematopoietic system occurs during aging and
      contributes to clinical consequences, including reduced competence of adaptive
      immunity and increased incidence of myeloid diseases. This has been linked to
      aging of the hematopoietic stem cell (HSC) compartment and has implications for
      clinical hematopoietic cell transplantation as prolonged periods of T-cell
      deficiency follow transplantation of adult mobilized peripheral blood (PB), the
      primary transplant source. Here, we examined the gene expression profiles of
      young and aged HSCs from human cord blood and adult mobilized PB, respectively,
      and found that Wnt signaling genes are differentially expressed between young and
      aged human HSCs, with less activation of Wnt signaling in aged HSCs. Utilizing
      the OP9-DL1 in vitro co-culture system to promote T-cell development under stable
      Notch signaling conditions, we found that Wnt signaling activity is important for
      T-lineage differentiation. Examination of Wnt signaling components and target
      gene activation in young and aged human HSCs during T-lineage differentiation
      revealed an association between reduced Wnt signal transduction, increasing age,
      and impaired or delayed T-cell differentiation. This defect in Wnt signal
      activation of aged HSCs appeared to occur in the early T-progenitor cell subset
      derived during in vitro T-lineage differentiation. Our results reveal that
      reduced Wnt signaling activity may play a role in the age-related intrinsic
      defects of aged HSCs and early hematopoietic progenitors and suggest that
      manipulation of this pathway could contribute to the end goal of improving T-cell
      generation and immune reconstitution following clinical transplantation. 

PMID- 24889653
TI  - Vaccination against smoking: an annotated agenda for debate. A review of
      scientific journals, 2001-13.
AB  - BACKGROUND AND AIMS: The ongoing development of novel nicotine vaccines makes it
      urgent to identify the normative questions around this innovative health
      technology against smoking. METHODS: A qualitative thematic analysis of peer
      reviewed papers on nicotine vaccination published between 2001 and 2013. RESULTS:
      In the scientific discourse, nicotine vaccination is presented in a
      neurobiological frame as a potent concept for (long-term) smoking cessation.
      Nicotine vaccination is also considered a hypothetical strategy to prevent
      nicotine addiction in minors. Ethical assessments are conducted for the use of
      nicotine vaccination in public health and clinical medicine. Whereas vaccination
      for primary prevention is usually associated with public health, the hypothetical
      case of nicotine prevention in minors is also assessed for individualized
      protection. Therapeutic and preventive applications are given uneven attention:
      the classic goal of vaccination (primary prevention in minors) receives
      methodical consideration and invokes lively debate. The unprecedented use of
      vaccination, namely smoking cessation, is left largely unattended in the ethical
      analyses. CONCLUSIONS: While health innovations such as nicotine vaccination need
      broad reflection to guide decisions on their further development and possible
      future implementations, only a small part of the ethical and social issues of
      this innovative technology has been discussed. For a debate to come into
      existence, a 'neurobio-psycho-socio-cultural' frame of smoking and quitting
      appears fruitful. Important topics for reflection are the human activities and
      social processes in a vaccine-supported quit attempt, next to respect for
      individuals, possible harms and questions of (global) justice and research
      ethics.

PMID- 24889655
TI  - Who would have thought that 'Jaws' also has brains? Cognitive functions in
      elasmobranchs.
AB  - Adaptation of brain structures, function and higher cognitive abilities most
      likely have contributed significantly to the evolutionary success of
      elasmobranchs, but these traits remain poorly studied when compared to other
      vertebrates, specifically mammals. While the pallium of non-mammalian vertebrates
      lacks the mammalian neocortical organization responsible for all cognitive
      abilities of mammals, several behavioural and neuroanatomical studies in recent
      years have clearly demonstrated that elasmobranchs, just like teleosts and other
      non-mammalian vertebrates, can nonetheless solve a multitude of cognitive tasks.
      Sharks and rays can learn and habituate, possess spatial memory; can orient
      according to different orientation strategies, remember spatial and
      discrimination tasks for extended periods of time, use tools; can imitate and
      learn from others, distinguish between conspecifics and heterospecifics,
      discriminate between either visual objects or electrical fields; can categorize
      visual objects and perceive illusory contours as well as bilateral symmetry. At
      least some neural correlates seem to be located in the telencephalon, with some
      pallial regions matching potentially homologous areas in other vertebrates where
      similar functions are being processed. Results of these studies indicate that the
      assessed cognitive abilities in elasmobranchs are as well developed as in
      teleosts or other vertebrates, aiding them in fundamental activities such as food
      retrieval, predator avoidance, mate choice and habitat selection. 

PMID- 24889654
TI  - The role of a preliminary PGY-3 in general surgery training.
AB  - INTRODUCTION: Even before the preliminary postgraduate year (PGY)-3 was
      eliminated from surgical residency, it had become increasingly difficult to fill
      general surgery PGY-4 vacancies. This ongoing need prompted the Association of
      Program Directors in Surgery (APDS) leadership to form a task force to study the
      possibility of requesting the restoration of the preliminary PGY-3 to
      Accreditation Council for Graduate Medical Education-approved general surgery
      residency programs. METHODS: The task force conducted a 10-year review of the
      APDS list serve to ascertain the number of advertised PGY-4 open positions.
      Following the review of the list serve, the task force sent IRB-approved
      electronic REDCap surveys to 249 program directors (PDs) in general surgery.
      RESULTS: The list serve review revealed more than 230 requests for fourth-year
      residents, a number that most likely underestimates the need, as such, vacancies
      are not always advertised through the APDS. A total of 119 PDs (~48%) responded.
      In the last 10 years, these 119 programs needed an average of 2 PGY-4 residents
      (range: 0-8), filled 1.3 positions (range: 0-7), and left a position unfilled 1.3
      times (range: 0-7). Methods for finding PGY-4 residents included making personal
      contacts with other PDs (52), posting on the APDS Topica List Serve (47), and
      using the APDS Web site for interested candidates on residency and fellowship job
      listings (52). Reasons for needing a PGY-4 resident included residents leaving
      the program (82), extra laboratory years (39), remediation (31), and approved
      program expansion (21), as well as other issues. Satisfaction scores for the
      added PGY-4 residents were more negative (43) than positive (30). Problems ranged
      from lack of preparation to professionalism. When queried as to an optimal number
      of preliminary residents needed nationally at the PGY-3 level, responses varied
      from 0 to 50 (34 suggested 10). CONCLUSIONS: The survey of PDs supports the need
      for the reintroduction of a limited number of Accreditation Council for Graduate
      Medical Education-approved preliminary PGY-3 positions in general surgery
      residency programs.

PMID- 24889656
TI  - Pilfering Eurasian jays use visual and acoustic information to locate caches.
AB  - Pilfering corvids use observational spatial memory to accurately locate caches
      that they have seen another individual make. Accordingly, many corvid cache
      protection strategies limit the transfer of visual information to potential
      thieves. Eurasian jays (Garrulus glandarius) employ strategies that reduce the
      amount of visual and auditory information that is available to competitors. Here,
      we test whether or not the jays recall and use both visual and auditory
      information when pilfering other birds' caches. When jays had no visual or
      acoustic information about cache locations, the proportion of available caches
      that they found did not differ from the proportion expected if jays were
      searching at random. By contrast, after observing and listening to a conspecific
      caching in gravel or sand, jays located a greater proportion of caches, searched
      more frequently in the correct substrate type and searched in fewer empty
      locations to find the first cache than expected. After only listening to caching
      in gravel and sand, jays also found a larger proportion of caches and searched in
      the substrate type where they had heard caching take place more frequently than
      expected. These experiments demonstrate that Eurasian jays possess observational
      spatial memory and indicate that pilfering jays may gain information about cache
      location merely by listening to caching. This is the first evidence that a corvid
      may use recalled acoustic information to locate and pilfer caches. 

PMID- 24889657
TI  - Simultaneous arrangement of up to three different molecules on the pore surface
      of a metal-macrocycle framework: cooperation and competition.
AB  - Porous crystals are excellent materials with potential spatial functions through
      molecular encapsulation within the pores. Co-encapsulation of multiple different
      molecules further expands their usability and designability. Herein we report the
      simultaneous arrangement of up to three different guest molecules, TTF
      (tetrathiafulvalene), ferrocene, and fluorene, on the pore surfaces of a porous
      crystalline metal-macrocycle framework (MMF). The position and orientation of
      adsorbed molecules arranged in the pore were determined by single-crystal X-ray
      diffraction analysis. The anchoring effect of hydrogen bonds between the hydroxy
      groups of the guest molecules and inter-guest cooperation and competition are
      significant factors in the adsorption behaviors of the guest molecules. This
      finding would serve as a design basis of multicomponent functionalized nanospaces
      for elaborate reactions that are realized in enzymes. 

PMID- 24889659
TI  - Synthesis and characterization of a uranium(II) monoarene complex supported by
      delta backbonding.
AB  - The low-temperature (<-35  degrees C) reduction of the trivalent uranium
      monoarene complex [{((Ad,Me) ArO)3 mes}U] (1), with potassium spheres in the
      presence of a slight excess of 2.2.2-cryptand, affords the quantitative
      conversion of 1 into the uranium(II) monoarene complex [K(2.2.2-crypt)][(((Ad,Me)
      ArO)3 mes)U] (1-K). The molecular and electronic structure of 1-K was established
      experimentally by single-crystal X-ray diffraction, variable-temperature (1) H
      NMR and X-band EPR spectroscopy, solution-state and solid-state magnetism
      studies, and optical absorption spectroscopy. The electronic structure of the
      complex was further investigated by DFT calculations. The complete body of
      evidence confirms that 1-K is a uranium(II) monoarene complex with a 5f (4)
      electronic configuration supported by delta backbonding and that the nearly
      reversible, room-temperature reduction observed for 1 at -2.495 V vs. Fc/Fc(+) is
      principally metal-centered. 

PMID- 24889658
TI  - Bioengineered silk gene delivery system for nuclear targeting.
AB  - Gene delivery research has gained momentum with the use of lipophilic vectors
      that mimic viral systems to increase transfection efficiency. Maintaining cell
      viability with these systems remains a major challenge. Therefore, biocompatible
      biopolymers that are designed by combining non-immunological viral mimicking
      components with suitable carrier are explored to address these limitations. In
      the present study, dragline silk recombinant proteins are modified with DNA
      condensing units and the proton sponge endosomal escape pathway is utilized for
      enhanced delivery. Transfection efficiency in a COS-7 cell line is enhanced
      compared to lipofectamine and polyethyleneimine (PEI), as is cell viability. 

PMID- 24889660
TI  - Acute forearm compartment syndrome following haemodialysis access fistula
      puncture in uraemia.
AB  - BACKGROUND: Acute compartment syndrome is a well-described surgical emergency
      that requires immediate diagnosis and operative intervention. Vascular access
      associated compartment syndrome is rarely reported in haemodialysis patients. The
      purpose of this article is to document evidence that catheter-related puncture,
      which results in arteriovenous fistula injury in uraemia, may cause acute forearm
      compartment syndrome. METHODS: Between September 2007 and September 2012, five
      consecutive patients presented to our section with tense swollen forearms with
      skin blistering, decreased hand sensation and reduced capillary return in the
      fingers. Their ages ranged from 65 to 81 years (mean 72.8 years). All of the
      patients underwent emergent exploration after the diagnosis of acute forearm
      compartment syndrome. The patients' details were reviewed. RESULTS: The time
      interval between dialysis completion and return to the emergency department
      ranged from 6 to 9 h (mean 7.4 h). During operation, the bleeding was found to
      originate from the site of the fistula puncture and was repaired with 9-0 nylon
      suture under microscopy. After adequate wound care, a reconstructive procedure
      with a split-thickness skin graft was performed in all of the five patients.
      There was no vascular or neurological deficit of the forearm or hand within the
      mean follow-up period of 14.8 months (range 12-18 months). CONCLUSIONS: In this
      series, we report five cases of forearm compartment syndrome in uraemia,
      secondary to bleeding from a catheter-related puncture of a haemodialysis access
      fistula. However, there is no case series that focuses upon this specific topic
      in the present literature. This problem deserves more attention.

PMID- 24889661
TI  - How do general practitioners engage with allied health practitioners to prevent
      falls in older people? An exploratory qualitative study.
AB  - AIM: To explore general practitioners' (GPs') perceptions about their use of
      Chronic Disease Management (CDM) items to access allied health interventions, in
      particular occupational therapy and physiotherapy, with the purpose of preventing
      falls, as well as to identify GP support needs with regard to development of
      partnerships with local allied health practitioners. METHOD: A qualitative study
      was conducted in the Sydney metropolitan area through individual semistructured
      interviews with eight GPs, which were recorded, transcribed and analysed
      thematically. RESULTS: Themes included (i) difficulties and opportunities
      associated with multidisciplinary care; (ii) potential for CDM items to be used
      to support falls prevention strategies; and (iii) the user-friendliness of the
      CDM items. CONCLUSION: Effective coordination of multidisciplinary care between
      GPs and allied health professionals was desired but difficult to achieve through
      the CDM system, making translation of falls prevention evidence into clinical
      practice challenging. Further education on falls prevention and CDM item
      modification is needed to bridge this gap.

PMID- 24889665
TI  - Dr. Ashraf Khir to serve as a co-editor for the European Region.

PMID- 24889663
TI  - Combining biomarkers to optimize patient treatment recommendations.
AB  - Markers that predict treatment effect have the potential to improve patient
      outcomes. For example, the OncotypeDX(r) RecurrenceScore(r) has some ability to
      predict the benefit of adjuvant chemotherapy over and above hormone therapy for
      the treatment of estrogen-receptor-positive breast cancer, facilitating the
      provision of chemotherapy to women most likely to benefit from it. Given that the
      score was originally developed for predicting outcome given hormone therapy
      alone, it is of interest to develop alternative combinations of the genes
      comprising the score that are optimized for treatment selection. However, most
      methodology for combining markers is useful when predicting outcome under a
      single treatment. We propose a method for combining markers for treatment
      selection which requires modeling the treatment effect as a function of markers.
      Multiple models of treatment effect are fit iteratively by upweighting or
      "boosting" subjects potentially misclassified according to treatment benefit at
      the previous stage. The boosting approach is compared to existing methods in a
      simulation study based on the change in expected outcome under marker-based
      treatment. The approach improves upon methods in some settings and has comparable
      performance in others. Our simulation study also provides insights as to the
      relative merits of the existing methods. Application of the boosting approach to
      the breast cancer data, using scaled versions of the original markers, produces
      marker combinations that may have improved performance for treatment selection.

PMID- 24889666
TI  - HVAD implantation in right atrium-to-right pulmonary artery configuration.

PMID- 24889667
TI  - Thoracic fit of the CardioWest artificial heart: a new technical solution.

PMID- 24889668
TI  - Device thrombosis with continuous-flow left ventricular assist devices: is Kounis
      syndrome involved?

PMID- 24889662
TI  - Guidelines for the use of NBCA in vascular embolization devised by the Committee
      of Practice Guidelines of the Japanese Society of Interventional Radiology
      (CGJSIR), 2012 edition.
AB  - Cyanoacrylates are a group of fast-acting adhesives. They form low viscosity
      liquids in the monomer state and instantly polymerize to become adhesive upon
      contact with ionic substances. Since the 1950s, they have been used around the
      world for industrial and household purposes. N-butyl cyanoacrylate (NBCA) is a
      cyanoacrylate that is commonly used for medical care, and the closure of skin
      wounds with NBCA has been found to promote hemostasis. However, in Japan, the
      intravascular injection of NBCA is considered to be off-label use, except during
      the treatment of gastric varices under endoscopy. The use of NBCA in
      embolotherapy is considered when the target vessels cannot be cannulated
      superselectively, for vascular diseases that require long segments of the target
      vessel to be embolized, or for patients in a hypocoagulable state. NBCA-based
      embolotherapy can be used to treat vascular malformations, acute hemorrhaging,
      tumors, and venous disease. The complications associated with NBCA-based
      embolotherapy include tissue ischemia, hemorrhaging, systemic or local reactions,
      and catheter adhesion to blood vessels. NBCA is mixed with Lipiodol to make it
      radiopaque and to adjust its polymerization time. Since there are various
      technical aspects to performing NBCA-based embolotherapy safely, it should be
      carried out by, or with the assistance of, proficient interventional
      radiologists.

PMID- 24889671
TI  - Disruptive innovations: the rise of the electronic cigarette.

PMID- 24889670
TI  - HPA stability for children in foster care: mental health implications and
      moderation by early intervention.
AB  - Research on stress-sensitive biological systems has typically focused on
      activation at one time, yet recent theories emphasize dynamic, context-specific
      adaptation. This study tested hypothesized calibration of one such system by
      examining both mean levels and longitudinal stability of daily cortisol-
      reflecting hypothalamic-pituitary-adrenal axis activation--in children exposed to
      high-risk versus lower-risk caregiving contexts. Context-specific effects of
      longitudinal cortisol profiles were addressed via relations with child
      psychiatric symptoms. Children from regular foster care, foster children
      participating in a family-based intervention, and community comparison children
      (n = 96 total) collected saliva samples for cortisol assay at 29 timepoints
      across 6+ years. High-risk (regular foster care) children showed lower and more
      variable cortisol levels than their lower-risk (treatment foster care, community
      comparison) counterparts. For the high-risk children only, higher and more stable
      cortisol related to elevated anxiety symptoms. Implications for contextual
      calibration of stress systems and family intervention mechanisms are discussed.

PMID- 24889672
TI  - Expression of growth-regulated oncogene-1, hepatocyte growth factor, platelet
      derived growth factor-AA and soluble E-selectin and their association with high
      risk human papillomavirus infection in squamous cell carcinoma of the uterine
      cervix.
AB  - The aim of the present study was to evaluate the clinical significance and
      prognostic value of growth-regulated oncogene-1 (GRO-1), hepatocyte growth factor
      (HGF), platelet-derived growth factor-AA (PDGF-AA), soluble E-selectin (sE
      selectin) and high-risk human papillomavirus (HPV; types 16, 18/45, 31 and
      33/52/58/67) infection in cervical squamous cell carcinoma (CSCC). A total of 426
      cases were enrolled in the present study, of which 292 cases were patients with
      CSCC, 43 were patients with cervical intraepithelial neoplasia (CIN) and 91 were
      healthy controls. Luminex xMAP technology was used to detect the serum levels of
      GRO-1, HGF, PDGF-AA and sE-selectin in all cases and two-channel fluorescence
      quantitative polymerase chain reaction was used to determine HPV DNA in cervical
      scrapings from CSCC and CIN patients. The results demonstrated that the serum
      levels of GRO-1, HGF and sE-selectin were significantly higher in patients with
      CSCC compared with patients with CIN and the healthy controls (P<0.0001).
      Compared with the CIN patients, the HPV positive rate in the CSCC patients
      significantly increased (P=0.013). The four factors were correlated with certain
      clinicopathological variables of CSCC patients to a certain degree (P<0.05) and
      the levels of HGF were closely associated with HPV infection (P=0.039). The
      receiver operating characteristic curves demonstrated that HGF obtained the
      highest diagnostic value compared with the other three factors. Multivariate Cox
      regression analysis demonstrated that the serum levels of HGF (P<0.0001), FIGO
      stage (P<0.0001) and pelvic lymph node metastasis (P=0.001) were independent
      prognostic factors in patients with CSCC, while high-risk HPV infection did not
      show any significance in this analysis. These results demonstrated that HGF may
      be a useful prognostic biomarker rather than high-risk HPV types in patients with
      CSCC. 

PMID- 24889673
TI  - Systems metabolic engineering of Escherichia coli for gram scale production of
      the antitumor drug deoxyviolacein from glycerol.
AB  - Deoxyviolacein is a microbial drug with biological activity against tumors, gram
      positive bacteria, and fungal plant pathogens. Here, we describe an Escherichia
      coli strain for heterologous production of this high-value drug from glycerol.
      Plasmid-based expression of the deoxyviolacein cluster vioABCE was controlled by
      the araBAD promoter and induction by L-arabinose. Through elimination of L
      arabinose catabolism in E. coli, the pentose sugar could be fully directed to
      induction of deoxyviolacein biosynthesis and was no longer metabolized, as
      verified by (13) C isotope experiments. Deletion of the araBAD genes beneficially
      complemented with previously described (i) engineering of the pentose phosphate
      pathway, (ii) chorismate biosynthesis, (iii) tryptophan biosynthesis, (iv)
      improved supply of L-serine, (v) elimination of tryptophan repression, and (vi)
      of tryptophan catabolism. Subsequent screening of the created next-generation
      producer E. coli dVio-8 identified glycerol as optimum carbon source and a level
      of 100 mg L(-1) of L-arabinose as optimum for induction. Transferred to a
      glycerol-based fed-batch process, E. coli dVio-8 surpassed the gram scale and
      produced 1.6 g L(-1) deoxyviolacein. With straightforward extraction from culture
      broth and purification by flash chromatography, deoxyviolacein was obtained at
      >99.5% purity. Biotechnol. Bioeng. 2014;111: 2280-2289. (c) 2014 Wiley
      Periodicals, Inc. 

PMID- 24889675
TI  - Application of a modified gaseous exposure system to the in vitro toxicological
      assessment of tobacco smoke toxicants.
AB  - Tobacco smoke is a complex mixture of over 6,000 individual chemical
      constituents. Approximately 150 of these have been identified as 'tobacco smoke
      toxicants' due to their known toxicological effects. A number of these toxicants
      are present in the gaseous phase of tobacco smoke. This presents a technical
      challenge when assessing the toxicological effects of these chemicals in vitro.
      We have adapted a commercially available tobacco smoke exposure system to enable
      the assessment of the contribution of individual smoke toxicants to the overall
      toxicological effects of whole mainstream cigarette smoke (WS). Here we present a
      description of the exposure system and the methodology used. We use the example
      of a gaseous tobacco smoke toxicant, ethylene oxide (EtO), a Group 1 IARC
      carcinogen and known mutagen, to illustrate how this methodology can be applied
      to the assessment of genotoxicity of gaseous chemicals in the context of WS. In
      the present study we found that EtO was positive in Salmonella typhimurium strain
      YG1042, a strain that is sensitive to tobacco smoke. However, EtO did not
      increase the mutagenicity of the WS mixture when it was added at greatly higher
      concentrations than those found typically in WS. The findings presented here
      demonstrate the suitability of this exposure system for the assessment of the
      mutagenic potential of gases in vitro. Whilst we have focused on tobacco smoke
      toxicants, this system has broad application potential in studying the biological
      effects of exposure to a wide range of gaseous compounds that are present within
      complex aerosol mixtures.

PMID- 24889674
TI  - Grafting MAP peptide to dental polymer inhibits MMP-8 activity.
AB  - Matrix metalloproteinases (MMPs) are a class of zinc and calcium-dependent
      endopeptidases responsible for degrading extracellular matrix (ECM) components.
      Their activity is critical for both normal biological function and pathological
      processes (Dejonckheere et al., Cytokine Growth Factor Rev 2011;22:73-81). In
      dental restorations, the release and subsequent acid activation of MMPs
      contributes to premature failure. In particular, MMP-8 accelerates degradation by
      cleaving the collagen matrix within the dentin substrate in incompletely
      infiltrated aged bonded dentin (Buzalaf et al., Adv Dent Res 2012;24:72-76),
      hastening the need for replacement of restorations. Therefore, development of a
      dental adhesive that better resists MMP-8 activity is of significant interest. We
      hypothesize that modification of the polymer surface with an inhibitor would
      disable MMP-8 activity. Here, we identify the metal abstraction peptide (MAP) as
      an inhibitor of MMP-8 and demonstrate that tethering MAP to methacrylate polymers
      effectively inhibits catalysis. Our findings indicate complete inhibition of MMP
      8 is achievable using a grafting approach. This strategy has potential to improve
      longevity of dental adhesives and other polymers and enable rational design of a
      new generation of biocompatible materials.

PMID- 24889676
TI  - Phase transitions of amorphous solid acetone in confined geometry investigated by
      reflection absorption infrared spectroscopy.
AB  - We investigated the phase transformations of amorphous solid acetone under
      confined geometry by preparing acetone films trapped in amorphous solid water
      (ASW) or CCl4. Reflection absorption infrared spectroscopy (RAIRS) and
      temperature-programmed desorption (TPD) were used to monitor the phase changes of
      the acetone sample with increasing temperature. An acetone film trapped in ASW
      shows an abrupt change in the RAIRS features of the acetone vibrational bands
      during heating from 80 to 100 K, which indicates the transformation of amorphous
      solid acetone to a molecularly aligned crystalline phase. Further heating of the
      sample to 140 K produces an isotropic solid phase, and eventually a fluid phase
      near 157 K, at which the acetone sample is probably trapped in a pressurized,
      superheated condition inside the ASW matrix. Inside a CCl4 matrix, amorphous
      solid acetone crystallizes into a different, isotropic structure at ca. 90 K. We
      propose that the molecularly aligned crystalline phase formed in ASW is created
      by heterogeneous nucleation at the acetone-water interface, with resultant
      crystal growth, whereas the isotropic crystalline phase in CCl4 is formed by
      homogeneous crystal growth starting from the bulk region of the acetone sample. 

PMID- 24889677
TI  - Impact of first-ever mild stroke on participation at 3 and 6 month post-event:
      the TABASCO study.
AB  - PURPOSE: This study focused on the relationships between cognition, participation
      and quality of life (QoL) among first-ever mild ischemic stroke patients 3 months
      post-event. We hypothesized that significant correlations exist between
      cognition, executive functions (EF), QoL and participation; and that EF and QoL
      will significantly contribute to participation beyond demographics and stroke
      severity at 3 and from 3 to 6 months post-stroke. METHODS: A prospective cohort
      study, recruiting consecutive first-ever stroke patients from a large tertiary
      hospital. The inclusion criteria were first event, mild stroke (NIHSS <= 5), and
      no previous significant neurological or cognitive impairment. In addition to
      assessment every 6 month at the hospital, an assessment battery was administered
      at home 3 months post-stroke. RESULTS: Participants showed mild to moderate
      difficulties in cognition and participation (n = 249). Low to moderate
      correlations were found between cognition and EF with participation (-0.380, p <
      0.05; r = 0.460, p < 0.001, respectively); and cognition with QoL (r = 0.421, p <
      0.001). EF and QoL contributed significantly to participation at 3 months (R(2) =
      0.961) and in addition education at 6 months (R(2) = 0.701). CONCLUSIONS:
      Participants after mild ischemic stroke experienced cognitive and EF difficulties
      that affect their participation and QoL. Further studies are needed of mild
      stroke survivors to enhance our understanding of the variables that affect
      participation. IMPLICATIONS FOR REHABILITATION: The findings of the current study
      have significant implications for the participation of people after mild stroke
      in the community. Health care systems in general and rehabilitation programs, in
      particular, do not consider that these clients need rehabilitation as most of
      them perform basic daily functions independently. Thus, although cognitive and EF
      deficits are found in people following even mild stroke, but are not externally
      apparent, these impairments are mostly neglected by the health care system. Mild
      stroke has long-term effects in most cases and effect family members as well. The
      implications of the study's results, as well as those of other studies, emphasize
      the necessity of follow-up and rehabilitation efforts at home and in the
      community. These efforts should focus on re-enabling the individual to
      participate in previous activities as much as possible and on providing support
      for family members. The strength of this study lies in the large number of
      participants who were evaluated at home in their natural environments. Studies of
      this kind are rarely performed in the participants' real-life settings, thus the
      current study provides an important perspective on the participation of this
      population in the community.

PMID- 24889678
TI  - Metastatic breast cancer: mechanisms and opportunities for cytology.
AB  - Despite significant advances in diagnosis, surgical techniques, general patient
      care, and local and systemic adjuvant therapies, metastatic disease remains the
      most critical condition limiting the survival of patients with breast cancer.
      Therefore, the development of effective treatment against late-arising metastasis
      has become the centre of clinical attention and is one of the current challenges
      in cancer research. A deeper understanding of the metastatic cascade is
      fundamental, and the need for repetitive tumour assessments for the evaluation of
      tumour evolution is a relatively new practice in routine medical care. As such,
      fine needle aspiration cytology (FNAC) is ideally placed to monitor biological
      changes in metastasis that may affect treatment and response. As FNAC is a
      minimally invasive method, it can be performed repeatedly with relatively little
      trauma, and selective ancillary tests can be applied to FNAC specimens, including
      for tumour whose primary nature is known. Herein, we review how the linear and
      parallel models explain metastatic dissemination, thus influencing therapeutic
      and clinical decisions, and how cytology, together with immunocytochemistry and
      molecular analysis, can be a tool for routine clinical practice and clinical
      trials aimed at metastatic disease with a special emphasis on breast cancer. 

PMID- 24889679
TI  - In situ growth of Ni(x)Cu(1-x) alloy nanocatalysts on redox-reversible rutile
      (Nb,Ti)O4 towards high-temperature carbon dioxide electrolysis.
AB  - In this paper, we report the in situ growth of Ni(x)Cu(1-x) (x = 0, 0.25, 0.50,
      0.75 and 1.0) alloy catalysts to anchor and decorate a redox-reversible
      Nb1.33Ti0.67O4 ceramic substrate with the aim of tailoring the electrocatalytic
      activity of the composite materials through direct exsolution of metal particles
      from the crystal lattice of a ceramic oxide in a reducing atmosphere at high
      temperatures. Combined analysis using XRD, SEM, EDS, TGA, TEM and XPS confirmed
      the completely reversible exsolution/dissolution of the Ni(x)Cu(1-x) alloy
      particles during the redox cycling treatments. TEM results revealed that the
      alloy particles were exsolved to anchor onto the surface of highly electronically
      conducting Nb1.33Ti0.67O4 in the form of heterojunctions. The electrical
      properties of the nanosized Ni(x)Cu(1-x)/Nb1.33Ti0.67O4 were systematically
      investigated and correlated to the electrochemical performance of the composite
      electrodes. A strong dependence of the improved electrode activity on the alloy
      compositions was observed in reducing atmospheres at high temperatures. Direct
      electrolysis of CO2 at the Ni(x)Cu(1-x)/Nb1.33Ti0.67O4 composite cathodes was
      investigated in solid-oxide electrolysers. The CO2 splitting rates were observed
      to be positively correlated with the Ni composition; however, the Ni0.75Cu0.25
      combined the advantages of metallic nickel and copper and therefore maximised the
      current efficiencies.

PMID- 24889680
TI  - Biocompatibility of root filling pastes used in primary teeth.
AB  - AIM: To evaluate the biocompatibility of two pastes designed to fill the root
      canals of primary teeth. METHODOLOGY: A study group of 54 mice received
      subcutaneous tissue implants of polyethylene tubes containing CTZ or calcium
      hydroxide paste or, as a negative control, empty tubes. Biocompatibility was
      evaluated on days 7, 21 and 63, yielding a total of nine groups of six animals
      each. Following the experimental intervals, the implant areas were removed and
      subjected to histologic processing. After the tissues were stained with HE and
      Masson trichrome, two pathologists performed a histologic analysis of the samples
      in a blinded manner. Collagen fibre formation, tissue thickness and inflammatory
      cell infiltration were analysed qualitatively. Quantitative morphometry was
      performed for the thickness, perimeter length and tissue area of the region in
      direct contact with the open tube. anova with the Tukey post-test and Kruskal
      Wallis analysis followed by Dunn's post-test, with significance established as P
      < 0.05, were used for data analysis. RESULTS: At 7 days, all groups had severe
      acute inflammatory infiltrates. Inflammation was reduced at 21 days in the CTZ
      paste group. Mild chronic inflammatory infiltrates were observed after 63 days in
      the CTZ and Ca(OH)2 paste groups; these groups also showed a significant decrease
      in collagen fibre density (P < 0.05), which was not observed in the control
      group. The average tissue thickness, perimeter length and area in contact with
      the tube decreased during the experimental periods in all groups. CONCLUSION: The
      CTZ and calcium hydroxide pastes demonstrated biocompatibility with subcutaneous
      tissue in this experimental model.

PMID- 24889681
TI  - Gas chromatography-electron ionization-mass spectrometry quantitation of valproic
      acid and gabapentin, using dried plasma spots, for therapeutic drug monitoring in
      in-home medical care.
AB  - A simple and sensitive gas chromatography-electron ionization-mass spectrometry
      (GC-EI-MS) method using dried plasma spot testing cards was developed for
      determination of valproic acid and gabapentin concentrations in human plasma from
      patients receiving in-home medical care. We have proposed that a simple, easy and
      dry sampling method is suitable for in-home medical patients for therapeutic drug
      monitoring. Therefore, in the present study, we used recently developed
      commercially available easy handling cards: Whatman FTA DMPK-A and Bond Elut DMS.
      In-home medical care patients can collect plasma using these simple kits. The
      spots of plasma on the cards were extracted into methanol and then evaporated to
      dryness. The residues were trimethylsilylated using N-methyl-N
      trimethylsilyltrifluoroacetamide. For GC-EI-MS analysis, the calibration curves
      on both cards were linear from 10 to 200 ug/mL for valproic acid, and from 0.5 to
      10 ug/mL for gabapentin. Intra- and interday precisions in plasma were both
      <=13.0% (coefficient of variation), and the accuracy was between 87.9 and 112%
      for both cards within the calibration curves. The limits of quantification were
      10 ug/mL for valproic acid and 0.5 ug/mL for gabapentin on both cards. We believe
      that the present method will be useful for in-home medical care.

PMID- 24889682
TI  - Cotton functionalized with peptides: characterization and synthetic methods.
AB  - Three approaches for the chemical ligation of peptides to cotton fibers are
      described and compared. This investigation was encouraged by the need to create
      peptide-decorated natural textiles, furnished with useful properties (e.g.
      antimicrobial activity). IR absorption spectroscopy is proved to be an easy and
      fast method to check the covalent anchorage of a peptide to cotton, whereas for a
      quantitative determination, a UV absorption method was employed. We also analyzed
      the usefulness of electron paramagnetic resonance spectroscopy to characterize
      our peptide-cotton conjugates.

PMID- 24889683
TI  - Subcutaneous granuloma annulare of the penis associated with a urethral anomaly:
      case report and review of the literature.
AB  - Granuloma annulare (GA) is an uncommon benign inflammatory skin condition, most
      often found on the extremities of young females. The subcutaneous variant of GA
      involving the penis is very rare. We report a case of subcutaneous GA associated
      with a urethral anomaly in a 15-year-old boy that persisted for a year. Treatment
      options are discussed with a review of the current literature. 

PMID- 24889684
TI  - Identification of an occupational skin disease according to German S 9 Par. 2 SGB
      VII during topical therapy with imiquimod.

PMID- 24889685
TI  - Inorganic elements in green sea turtles (Chelonia mydas): relationships among
      external and internal tissues.
AB  - Inorganic elements from anthropogenic sources have entered marine environments
      worldwide and are detectable in marine organisms, including sea turtles.
      Threatened and endangered classifications of sea turtles have heretofore made
      assessments of contaminant concentrations difficult because of regulatory
      restrictions on obtaining samples using nonlethal techniques. In the present
      study, claw and skin biopsy samples were examined as potential indicators of
      internal tissue burdens in green sea turtles (Chelonia mydas). Significant
      relationships were observed between claw and liver, and claw and muscle
      concentrations of mercury, nickel, arsenic, and selenium (p < 0.05). Similarly,
      significant relationships were observed between skin biopsy concentrations and
      those in liver, kidney, and muscle tissues for mercury, arsenic, selenium, and
      vanadium (p < 0.05). Concentrations of arsenic, barium, chromium, nickel,
      strontium, vanadium, and zinc in claws and skin biopsies were substantially
      elevated when compared with all other tissues, indicating that these highly
      keratinized tissues may represent sequestration or excretion pathways.
      Correlations between standard carapace length and cobalt, lead, and manganese
      concentrations were observed (p < 0.05), indicating that tissue concentrations of
      these elements may be related to age and size. Results suggest that claws may
      indeed be useful indicators of mercury and nickel concentrations in liver and
      muscle tissues, whereas skin biopsy inorganic element concentrations may be
      better suited as indicators of mercury, selenium, and vanadium concentrations in
      liver, kidney, and muscle tissues of green sea turtles.

PMID- 24889687
TI  - Upregulation of FGFR1 expression is associated with parathyroid carcinogenesis in
      HPT-JT syndrome due to an HRPT2 splicing mutation.
AB  - Mutations of the HRPT2 gene, which are responsible for hyperparathyroidism-jaw
      tumor (HPT-JT) syndrome, have been implicated in the development of a high
      proportion of parathyroid carcinomas. The aim of this study was to investigate
      differences in expression of the most important genes connected with parathyroid
      carcinoma between HPT-JT syndrome due to an HRPT2 splicing mutation, normal
      parathyroid tissue and sporadic parathyroid adenoma. Total RNAs were extracted
      from parathyroid carcinoma in HPT-JT syndrome harbouring HRPT2 splicing mutation
      or sporadic parathyroid adenoma and normal parathyroid gland, and subjected to
      Illumina DASL-based gene expression assay. Unsupervised hierarchical clustering
      analysis was used to compare gene expression in HPT-JT syndrome, sporadic
      parathyroid adenoma and normal parathyroid glands. We identified differentially
      regulated genes in HPT-JT syndrome and sporadic parathyroid adenoma relative to
      normal parathyroid glands using a combination of Welch's t-test and fold-change
      analysis. Quantitative PCR, RT-PCR and IHC were used for validation. Sixteen
      genes differentially regulated in the parathyroid carcinoma were associated with
      signal pathways, MAPK, regulation of actin cytoskeleton, prostate cancer and
      apoptosis. FGFR1 expression was confirmed to be significantly upregulated by
      validation experiments. Our gene expression profiling experiments suggest that
      upregulated FGFR1 expression appears to be associated with parathyroid carcinoma
      in HPT-JT syndrome due to an HRPT2 splicing mutation. 

PMID- 24889686
TI  - Multiple recognition of RXLR effectors is associated with nonhost resistance of
      pepper against Phytophthora infestans.
AB  - Nonhost resistance (NHR) is a plant immune response to resist most pathogens. The
      molecular basis of NHR is poorly understood, but recognition of pathogen
      effectors by immune receptors, a response known as effector-triggered immunity,
      has been proposed as a component of NHR. We performed transient expression of 54
      Phytophthora infestansRXLR effectors in pepper (Capsicum annuum) accessions. We
      used optimized heterologous expression methods and analyzed the inheritance of
      effector-induced cell death in an F2 population derived from a cross between two
      pepper accessions. Pepper showed a localized cell death response upon inoculation
      with P. infestans, suggesting that recognition of effectors may contribute to NHR
      in this system. Pepper accessions recognized as many as 36 effectors. Among the
      effectors, PexRD8 and Avrblb2 induced cell death in a broad range of pepper
      accessions. Segregation of effector-induced cell death in an F2 population
      derived from a cross between two pepper accessions fit 15:1, 9:7 or 3:1 ratios,
      depending on the effector. Our genetic data suggest that a single or two
      independent/complementary dominant genes are involved in the recognition of RXLR
      effectors. Multiple loci recognizing a series of effectors may underpin NHR of
      pepper to P. infestans and confer resistance durability.

PMID- 24889688
TI  - Percutaneous single-fiber reflectance spectroscopy of canine intervertebral disc:
      is there a potential for in situ probing of mineral degeneration?
AB  - BACKGROUND AND OBJECTIVES: Intervertebral disc herniation is a common disease in
      chondrodystrophic dogs, and a similar neurologic condition also occurs in humans.
      Percutaneous laser disc ablation (PLDA) is a minimally invasive procedure used
      increasingly for prevention of disc herniation. Currently, PLDA is performed on
      thoracolumbar discs with the same laser energy applied regardless of the
      differing extent of degeneration among mineralized discs. In a previous study
      performed on 15 normal and 6 degenerated intervertebral discs in
      chondrodystrophoid canine species, it was demonstrated that percutaneous single
      fiber reflectance spectroscopy (SfRS) detected increased light scattering from
      mineralized intervertebral discs when comparing to normal discs. The objective of
      this study is to evaluate how SfRS evaluation of mineralized discs in situ fairs
      with X-ray radiography and computed tomography (CT) diagnoses and if SfRS sensing
      of the scattering changes correlates with the level of mineral degeneration in
      nucleus pulposus. MATERIALS AND METHODS: Percutaneous SfRS was performed on a
      total of 28 intervertebral discs of three dogs post-mortem, through a 20 gauge
      spinal needle standard to PLDA. The raw SfRS measurement was normalized to
      extract a dimension-less spectral intensity profile, from which the average over
      600-900 nm was used as the SfRS intensity index to compare among the measured
      discs. The discs were imaged prior to percutaneous SfRS by radiography and CT,
      and harvested after percutaneous SfRS for histopathologic examinations. RESULTS:
      Five among 10 discs of dog #1, six among 9 discs of dog #2, and nine out of 9
      discs of dog #3 were determined by histopathology to have central focal or multi
      focal areas of mineralization occupying 5-75% of the examined area of nucleus
      pulposus. The overall numbers of discs with detectable and undetectable central
      mineralization were 20 and 8, respectively. CT resulted in one false positive
      (FP) and four false negative (FN) diagnoses for dog #1, three FP and zero FN
      diagnoses for dog #2, and zero FP and one FN diagnosis for dog #3. Of the total
      28 discs the CT had an overall positive predictive value (PPV) of 78.8% and an
      overall negative predictive value (NPV) of 44.4%. X-ray radiography gave five FN
      diagnoses for dog #1, two FN diagnoses for dog #2, and eight FN diagnoses for dog
      #3. Of the total 28 discs the radiography had an overall PPV of 100% and an
      overall NPV of 30.4%. The receiver-operating-characteristic analysis of the SfRS
      measurement was performed on 24 discs that had a central mineralization not
      greater than 50%. An area-under-curve of 0.6758 infers that the SfRS intensity
      weakly indicates the level of mineralization. CONCLUSIONS: Percutaneous SfRS may
      be useful as an in situ sensing tool for assessing the level of mineral
      degeneration in intervertebral discs for the prospect of disc-specific dosage
      adjustment in PLDA.

PMID- 24889690
TI  - Estimating phenotypic selection in age-structured populations by removing
      transient fluctuations.
AB  - An extension of the selection differential in the Robertson-Price equation for
      the mean phenotype in an age-structured population is provided. Temporal changes
      in the mean phenotype caused by transient fluctuations in the age-distribution
      and variation in mean phenotype among age classes, which can mistakenly be
      interpreted as selection, will disappear if reproductive value weighting is
      applied. Changes in any weighted mean phenotype in an age-structured population
      may be decomposed into between- and within-age class components. Using
      reproductive value weighting the between-age class component becomes pure noise,
      generated by previous genetic drift or fluctuating selection. This component,
      which we call transient quasi-selection, can therefore be omitted when estimating
      age-specific selection on fecundity or viability within age classes. The final
      response can be computed at the time of selection, but can not be observed until
      lifetime reproduction is realized unless the heritability is one. The generality
      of these results is illustrated further by our derivation of the selection
      differential for the continuous time age-structured model with general age
      dependent weights. A simple simulation example as well as estimation of selection
      components in a house sparrow population illustrates the applicability of the
      theory to analyze selection on the mean phenotype in fluctuating age-structured
      populations. 

PMID- 24889689
TI  - "Maybe they have found something new" participants' views on returning cohort
      psychosocial survey results.
AB  - BACKGROUND: Although greater attention is currently being paid to participants in
      research, no studies have dealt so far with the issue of returning aggregate
      psychosocial results to cohort participants. OBJECTIVE: (i) To explore
      participants' views about disclosure of the aggregate results of a French
      national psychosocial cohort survey on the epidemiology of preventive behaviour
      in women from families with a hereditary breast cancer risk. (ii) To assess
      whether it is worth consulting participants before designing the disclosure
      process. DESIGN: A qualitative study using semi-structured face-to-face
      interviews and a thematic analysis based on Grounded Theory methods.
      PARTICIPANTS: Nineteen interviews were conducted with cancer-free female BRCA
      mutation carriers/non-carriers aged 31-79 who had participated in a cohort survey
      by answering self-administered questionnaires. RESULTS: Participants showed
      considerable interest in the issue of result disclosure. The preferences
      expressed about disclosure were rarely relevant to the topic investigated,
      however, as they often focused on medical knowledge about BRCA and not on the
      psychosocial findings obtained. This confusion may have been due to the
      participants' experience of the survey procedures, including its longitudinal
      nature, the occurrence of very few interactions with the investigators and the
      wide range of topics addressed in the questionnaires. CONCLUSION: Investigators
      should ascertain participants' expectations and preferences by consulting them
      before disclosing the results obtained. Although the disclosure process may not
      meet participants' expectations completely, consultation is the key to preventing
      them from having irrealistic expectations about the information they are going to
      receive.

PMID- 24889691
TI  - Disseminated nocardiosis during systemic steroid therapy for the prevention of
      esophageal stricture after endoscopic submucosal dissection.
AB  - An 85-year-old man underwent endoscopic submucosal dissection for a large
      superficial esophageal epithelial neoplasm, which required removal of 95% of the
      circumference of the esophageal mucosa. Steroids were given orally to prevent
      esophageal stricture starting on day 3 postoperatively. In the 6th week of
      steroid treatment, he developed high fever without other symptoms. Chest computed
      tomography revealed a nodular lesion in the lung. Sputum sample showed Gram
      positive, branching, filamentous bacteria, and a diagnosis of nocardiosis was
      suspected. Brain magnetic resonance imaging revealed multiple focal lesions which
      indicated dissemination of nocardiosis. Trimethoprim-sulfamethoxazole was
      immediately started, which led to the disappearance of pulmonary and cerebral
      nocardiosis with alleviation of fever. Recently, oral steroid treatment has been
      widely used for the prevention of esophageal stricture. However, the present case
      indicates the risk of life-threatening infection and the importance of close
      monitoring of this treatment. 

PMID- 24889692
TI  - CPAP and heart failure.

PMID- 24889693
TI  - miRNA-940 reduction contributes to human Tetralogy of Fallot development.
AB  - Tetralogy of Fallot (TOF) is a complex congenital heart defect and the microRNAs
      regulation in TOF development is largely unknown. Herein, we explored the role of
      miRNAs in TOF. Among 75 dysregulated miRNAs identified from human heart tissues,
      miRNA-940 was the most down-regulated one. Interestingly, miRNA-940 was most
      highly expressed in normal human right ventricular out-flow tract comparing to
      other heart chambers. As TOF is caused by altered proliferation, migration and/or
      differentiation of the progenitor cells of the secondary heart field, we isolated
      Sca-1(+) human cardiomyocyte progenitor cells (hCMPC) for miRNA-940 function
      analysis. miRNA-940 reduction significantly promoted hCMPCs proliferation and
      inhibited hCMPCs migration. We found that JARID2 is an endogenous target
      regulated by miRNA-940. Functional analyses showed that JARID2 also affected
      hCMPCs proliferation and migration. Thus, decreased miRNA-940 affects the
      proliferation and migration of the progenitor cells of the secondary heart field
      by targeting JARID2 and potentially leads to TOF development. 

PMID- 24889694
TI  - Inequalities in health care among patients with type 2 diabetes by individual
      socio-economic status (SES) and regional deprivation: a systematic literature
      review.
AB  - INTRODUCTION: Quality of care could be influenced by individual socio-economic
      status (SES) and by residential area deprivation. The objective is to synthesize
      the current evidence regarding inequalities in health care for patients with Type
      2 diabetes mellitus (Type 2 DM). METHODS: The systematic review focuses on
      inequalities concerning process (e.g. measurement of HbA1c, i.e. glycolised
      haemoglobin) and intermediate outcome indicators (e.g. HbA1c level) of Type 2
      diabetes care. In total, of n = 886 publications screened, n = 21 met the
      inclusion criteria. RESULTS: A wide variety of definitions for 'good quality
      diabetes care', regional deprivation and individual SES was observed. Despite
      differences in research approaches, there is a trend towards worse health care
      for patients with low SES, concerning both process of care and intermediate
      outcome indicators. Patients living in deprived areas less often achieve
      glycaemic control targets, tend to have higher blood pressure (BP) and worse
      lipid profile control. CONCLUSION: The available evidence clearly points to the
      fact that socio-economic inequalities in diabetes care do exist. Low individual
      SES and residential area deprivation are often associated with worse process
      indicators and worse intermediate outcomes, resulting in higher risks of
      microvascular and macrovascular complications. These inequalities exist across
      different health care systems. Recommendations for further research are provided.

PMID- 24889695
TI  - Software eyes for protein post-translational modifications.
AB  - Post-translational modifications (PTMs) are critical to almost all aspects of
      complex processes of the cell. Identification of PTMs is one of the biggest
      challenges for proteomics, and there have been many computational studies for the
      analysis of PTMs from tandem mass spectrometry (MS/MS). Most early PTM
      identification studies have been performed by matching MS/MS data to protein
      databases, using database search tools, but they are prohibitively slow when a
      large number of PTMs is given as a search parameter. In this article, we present
      recent developments to search for more types of PTMs and to speed up the search,
      and discuss many computational issues and solutions in terms of identifying
      multiply modified peptides or searching for all possible modifications at once in
      unrestrictive mode. Apart from the most common type of PTMs involving covalent
      addition of functional groups to proteins, PTMs such as disulfide linkage require
      dedicated software for the analysis because they may involve cross-linking
      between two different parts of proteins. Finally, methods for identification of
      protein disulfide bonds are presented.

PMID- 24889697
TI  - Disruption of vitellogenesis and spermatogenesis by triclabendazole (TCBZ) in a
      TCBZ-resistant isolate of Fasciola hepatica following incubation in vitro with a
      P-glycoprotein inhibitor.
AB  - A study has been carried out to investigate whether the action of triclabendazole
      (TCBZ) against Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)
      linked drug efflux pumps. The Sligo TCBZ-resistant fluke isolate was used for
      these experiments and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL].
      In the first experiment, flukes were initially incubated for 2 h in R(+)-VPL (100
      MU m), then incubated in R(+)-VPL+triclabendazole sulphoxide (TCBZ.SO) (50 MUg mL
      1, or 133.1 MU m) until flukes ceased movement (at 9 h post-treatment). In a
      second experiment, flukes were incubated in TCBZ.SO alone and removed from the
      incubation medium following cessation of motility (after 15 h). In the third
      experiment, flukes were incubated for 24 h in R(+)-VPL on its own. Changes to the
      testis tubules and vitelline follicles following drug treatment and following Pgp
      inhibition were assessed by means of light microscope histology and transmission
      electron microscopy. Incubation of the Sligo isolate in either R(+)-VPL or
      TCBZ.SO on their own had a limited impact on the morphology of the two tissues.
      Greater disruption was observed when the drugs were combined, in terms of the
      block in development of the spermatogenic and vitelline cells and the apoptotic
      breakdown of the remaining cells. Sperm formation was severely affected and
      abnormal. Large spaces appeared in the vitelline follicles and synthesis of shell
      protein was disrupted. The results of this study support the concept of altered
      drug efflux in TCBZ-resistant flukes and indicate that drug transporters may play
      a role in the development of drug resistance.

PMID- 24889696
TI  - The pattern of xylan acetylation suggests xylan may interact with cellulose
      microfibrils as a twofold helical screw in the secondary plant cell wall of
      Arabidopsis thaliana.
AB  - The interaction between xylan and cellulose microfibrils is important for
      secondary cell wall properties in vascular plants; however, the molecular
      arrangement of xylan in the cell wall and the nature of the molecular bonding
      between the polysaccharides are unknown. In dicots, the xylan backbone of beta
      (1,4)-linked xylosyl residues is decorated by occasional glucuronic acid, and
      approximately one-half of the xylosyl residues are O-acetylated at C-2 or C-3. We
      recently proposed that the even, periodic spacing of GlcA residues in the major
      domain of dicot xylan might allow the xylan backbone to fold as a twofold helical
      screw to facilitate alignment along, and stable interaction with, cellulose
      fibrils; however, such an interaction might be adversely impacted by random
      acetylation of the xylan backbone. Here, we investigated the arrangement of
      acetyl residues in Arabidopsis xylan using mass spectrometry and NMR. Alternate
      xylosyl residues along the backbone are acetylated. Using molecular dynamics
      simulation, we found that a twofold helical screw conformation of xylan is stable
      in interactions with both hydrophilic and hydrophobic cellulose faces. Tight
      docking of xylan on the hydrophilic faces is feasible only for xylan decorated on
      alternate residues and folded as a twofold helical screw. The findings suggest an
      explanation for the importance of acetylation for xylan-cellulose interactions,
      and also have implications for our understanding of cell wall molecular
      architecture and properties, and biological degradation by pathogens and fungi.
      They will also impact strategies to improve lignocellulose processing for
      biorefining and bioenergy.

PMID- 24889698
TI  - S=1/2 one-dimensional random-exchange ferromagnetic zigzag ladder, which exhibits
      competing interactions in a critical regime.
AB  - The synthesis, crystal structure, and magnetic properties (from a combined
      experimental and First-Principles Bottom-Up theoretical study) of the new
      compound catena-dichloro(2-Cl-3Mpy)copper(II), 1, [2-Cl-3Mpy=2-chloro-3
      methylpyridine] are described and rationalized. Crystals of 1 present well
      isolated magnetic 1D chains (no 3D order was experimentally observed down to 1.8
      K) and magnetic frustration stemming from competing ferromagnetic nearest
      neighbor (J(NN)) interactions and antiferromagnetic next-nearest neighbor
      (J(NNN)) interactions, in which alpha=J(NNN)/J(NN) <-0.25. These magnetic
      interactions give rise to a unique magnetic topology: a two-leg zigzag ladder
      composed of edge-sharing up-down triangles with antiferromagnetic interactions
      along the rails and ferromagnetic interactions along the zigzag chain that
      connects the rails. Crystals of 1 also present a random distribution of the 2-Cl
      3Mpy groups, which are arranged in two different orientations, each with a 50 %
      occupancy. This translates into a random static structural disorder within each
      chain by virtue of which the value of the J(NN) magnetic interactions can
      randomly take one of the following three values: 53, 36, and 16 cm(-1). The
      structural disorder does not affect the J(NNN) value, which in all cases is
      approximately -9 cm(-1). A proper statistical treatment of this disorder provides
      a computed magnetic susceptibility curve that reproduces the main features of the
      experimental data.

PMID- 24889699
TI  - Regional disparities affect treatment and survival of patients with intrahepatic
      cholangiocarcinoma--a Texas Cancer Registry analysis.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed at advanced
      stage and few patients qualify for resection. Effects of barriers to access on
      outcomes are unknown. We hypothesized that income and rural residence account for
      delays in treatment and decreased survival. METHODS: Texas Cancer Registry was
      queried for ICC patients from 2000 to 2008. Median household income (MHI) and
      urban/rural status were analyzed. Regression analyses were performed for (1) time
      to- treatment (TTT), and (2) overall survival (OS). RESULTS: Among 1,089
      patients, 20.2% patients resided in rural areas and MHI ranged $24,497
      $81,113/year. Primary treatment included surgery for 9.5%, radiation 5.4% and
      chemotherapy 21.0%. Median TTT was 29 (range 0-235) days. Patients from low
      income areas were less likely to receive treatment (below median MHI, 29.7% vs.
      above median MHI, 37.5%%; P = 0.007). MHI was associated with TTT (per
      $10,000/year: hazard ratio (HR) = 1.05; 95% CI: 1.01-1.09). Adjusting for stage,
      MHI was associated with OS (per $10,000/year: HR = 0.97; 95%CI: 0.94-0.99). Rural
      residence was neither associated with TTT nor OS. CONCLUSION: Overall treatment
      rates for ICC patients are low. Regional income, not urbanization was associated
      treatment and survival independent of stage. Further research is needed to
      determine how regional prosperity relates to care access.

PMID- 24889700
TI  - Genome-wide transcriptome analysis of Arabidopsis response to sulfur dioxide
      fumigation.
AB  - Sulfur dioxide (SO2) supplies the basic sulfur element to promote plant growth,
      yet at the same time it is a harmful air pollutant. Currently, the mechanisms of
      plant adaptation to SO2 stress are largely unknown. Pathways of SO2 metabolism, a
      range of networks of interacting regulatory signals and defense mechanisms
      triggered in resistance to SO2 stress, have not yet been clarified. We performed
      transcriptome analysis of Arabidopsis plants fumigated with 30 mg m(-3) SO2 for
      72 h and untreated controls using microarrays. This identified 2,780
      significantly up- or down-regulated genes in plants response to SO2 stress,
      indicating a possible genome-scale reprogramming of the transcriptome.
      Significant changes in the transcript abundance of genes that participated in SO2
      metabolic pathways indicated that numerous sulfites were involved in sulfur
      assimilatory pathways directly and away from sulfite oxidative pathways.
      Furthermore, the up-regulation of components involved in reactive oxygen species
      generating and scavenging pathways demonstrated altered redox homeostasis.
      Transcripts encoding key components in nitric oxide biosynthesis pathways were
      simultaneously up-regulated by SO2 exposure. In addition, transcripts associated
      with putative biotic stress were also up-regulated. Therefore, SO2 evokes a
      comprehensive reprogramming of metabolic pathways, consistent with up-regulation
      of transcripts involved in tolerance and defense mechanisms, in Arabidopsis. 

PMID- 24889701
TI  - [The cost of applying the Dependency Law to Alzheimer disease].
AB  - AIM: To calculate the formal cost of social care for people with Alzheimer
      disease according to the implementation of the dependency law in Gipuzkoa
      (Spain). METHOD: A retrospective observational study was carried out of the
      database of the Dependency Care Services of Gipuzkoa from 2007 to 2012, using a
      prevalence-based bottom-up approach. RESULTS: The average annual formal cost per
      person was ?11,730. The annual population cost was ?34.7 million, representing
      19% of the annual expenditure corresponding to the dependency law and 29% of the
      total cost of Alzheimer disease. CONCLUSIONS: Despite the implementation of the
      new law, most of the burden of the disease is bourne by the family.

PMID- 24889703
TI  - [Enhancing public health through physical education in Spain: a call to action].

PMID- 24889702
TI  - Gender inequalities in the medical profession: are there still barriers to women
      physicians in the 21st century?
AB  - AIM: To analyze women's advancement compared with that of men and to determine
      whether advancement in hierarchical status differs from advancement in the
      professional recognition achieved by women from 1996 to 2008. METHODS: A
      retrospective study was carried in Hospital Clinic in Barcelona. We analyzed data
      on temporary and permanent positions, hierarchy, promotions, specialty, age, and
      sex among the participants. RESULTS: The female-to male ratio among trainee
      medical specialists was higher than 1 throughout the study period. After
      completion of specialist training, the proportion of women with temporary
      contracts more than doubled that of men. Less than 50% of women achieved
      permanent positions compared with 70% of men. For permanent non-hierarchical and
      hierarchical positions, the female-to-male ratio gradually decreased from 0.5 to
      below 0.2. Although more than 50% of trainee specialists were women, the number
      of female consultants remained 25% lower than that of men. In 2008, the final
      year of the study, the percentage of women who had achieved the grade of senior
      consultant was one-third that of men (29.5% of men vs 10.9% of women; p<0.0001).
      CONCLUSIONS: The significant differences in medical positions held by men and
      women illustrate the 'leaky pipeline phenomenon', consisting of a
      disproportionately low number of women achieving leading medical positions. The
      full potential of the increasing number of women physicians will not be reached
      without continuing efforts to improve the hospital medicine environment.

PMID- 24889704
TI  - An efficient nanomaterial-based electrochemical biosensor for sensitive
      recognition of drug-resistant leukemia cells.
AB  - A novel electrochemical cytosensor was developed for the fast and high
      sensitivity recognition of drug-resistant leukemia K562/ADM cells based on the P
      glycoprotein (P-gp) expression level on a cell membrane. The nanocomposite
      interface of the gold nanoparticles/polyaniline nanofibers (AuNPs/PANI-NF) was
      chosen to design the biosensor for electrochemical detection. Au/PANI-NF-based
      cytosensors coated with anti-P-glycoprotein (anti-P-gp) molecules could provide a
      biomimetic interface for the immunosensing of cell surface P-glycoprotein, and
      thus could capture the over-expression P-gp cells. Transmission electron
      microscopy (TEM) indicated that the gold nanoparticles were uniformly anchored
      along the structure of the PANI-NF surface, displaying fibrillar morphology with
      a diameter of ~70 nm, and atomic force microscopy (AFM) further presented the
      morphology of the nanocomposite film. Owing to the high affinity of anti-P-gp for
      leukemia K562/ADM cells of the propounded sensing platform, the proposed
      biosensor exhibited excellent analytical performance for leukemia K562/ADM cells,
      ranging from 1.6 * 10(2) to 1.6 * 10(6) cells per mL with a detection limit of 80
      cells per mL. Recovery experiments indicated that the sensitivity reported here
      is suitable for practical application. The cell surface P-gp expression level was
      analysed by flow cytometric experiments, which confirmed the above recognized
      result. This strategy is also a cost-effective and convenient operation, implying
      great promise for the sensitive recognition of cancer cells and cell surface
      receptors; thus, it is helpful in cancer diagnosis. 

PMID- 24889705
TI  - [Is the medical exam according to S25 SGB V still currently valid?].

PMID- 24889706
TI  - [Periodic health examinations - an international comparison].
AB  - BACKGROUND: The purpose of periodic health examinations is to prevent disease
      through early intervention and through stratifying individual patients' health
      risk. The German health examination as defined in section 25 of the Social Code
      Book V (Sozialgesetzbuch V) seems to be outdated in many respects. In order to
      develop an alternative to the current German system an international comparison
      of periodic health examinations in other healthcare systems is useful. OBJECTIVE:
      The study investigates the measures taken for primary prevention of
      cardiovascular disease in seven countries. Content, implementation and
      organisation of the various programmes are analysed in the present paper.
      METHODS: The present study was designed as a qualitative multiple case study. The
      collection of data on cardiovascular screening programmes in the seven different
      healthcare systems in this study relies on information publicly available on the
      Internet. The data were entered into a matrix which had been created prior to the
      data collection and which covers the relevant points of screening. Finally, the
      data were triangulated using guided telephone interviews with key informants. One
      general practitioner (GP) was interviewed per country. The measures taken in the
      respective healthcare systems were then compared and analysed. RESULTS: The
      measures taken in the countries studied for the primary prevention of
      cardiovascular disease are heterogeneous. The structures range from guideline
      recommendations (Castilla y Leon, Switzerland, Norway), and incentive payments
      for doctors (British Columbia), to opportunistic and population-based programmes
      (Germany and England, and Group Health in the US). The American health
      maintenance organisation Group Health offers an established, evidence-based
      programme whereas the German health examination dates back to a time when
      evidence-based medicine was not yet established and is therefore relatively
      outdated. DISCUSSION: Despite scientific evidence of primary prevention of
      cardiovascular disease, evidence-based measures cannot be found in all the
      healthcare systems analysed. The paper discusses sociocultural and political
      aspects as influencing factors on prevention programmes.

PMID- 24889707
TI  - [The periodic health examination: from law to the directive of the German Federal
      Joint Committee (G-BA)].
AB  - Since 1989 a periodic health examination beginning at the age of 35 for the early
      detection of "common diseases" (especially cardiovascular and kidney diseases as
      well as diabetes) by means of history-taking, physical examination, blood and
      urine tests and counselling has been available in Germany. Altogether, the
      respective directive of the Federal Joint Committee (G-BA) was revised six times,
      but a substantive change took place only once (i. e., the cancellation of uric
      acid, creatinine, and resting ECG in 1999). However, additional examinations
      (e.g., glaucoma screening) were not added to the health check after systematic
      assessments of the evidence were completed. In the mid-1990s, several evaluations
      were performed which showed that new diagnoses were established in a significant
      proportion of patients, and measures were initiated such as nutrition
      counselling. A patient-relevant benefit in terms of avoided adverse events (such
      as heart attacks) could, however, not be demonstrated due to methodological
      reasons. Criticism of the health examination is not new, in particular concerning
      the lack of evidence of benefit for the diagnostic procedures of the health
      examination. A draft law issued by the former Federal Government proposing an
      amendment to the health examination has recently been rejected in the Bundesrat
      (upper house of the German parliament). 

PMID- 24889708
TI  - [The Bremen periodic health exam - feasibility of a new concept].
AB  - BACKGROUND: All members of the Statutory Health Insurance are entitled to receive
      preventive health examinations. The current concept, however, does not take
      individual risk factors into account systematically. To improve this, the "Bremen
      Health Examination" was developed. The central component is a screening
      questionnaire to be completed by the patient, which is stratified by age, i.e.,
      35 to 69 years and >= 70 years. The feasibility and acceptance of this concept
      have been assessed. METHODS: In a prospective observational study, a selected
      sample of general practitioners (GPs) was asked to implement the questionnaires
      during all preventive health examinations within a four-week period. The GPs
      subsequently answered content-related questions as well as Likert-scaled
      questions on the relevance of the issues addressed, and the feasibility of the
      new concept. RESULTS: 17 out of 20 GPs approached for the study included a total
      of 171 patients. On average, the patients in the two groups were 52 and 75 years
      of age, respectively, and answered 4.4 prompting questions positively. Age and
      gender had no significant effect on the frequency of "positively" answered
      questions. Implementing the questionnaire extended the duration of the health
      examination, however, GPs overall rated the time required for discussing newly
      assessed problems as adequate (four-level Likert scale, 1=yes; 4=no; O 1.59; SD
      0.77). CONCLUSION: The implementation of the Bremen Health Examination appears to
      be feasible from the GP perspective.

PMID- 24889709
TI  - [Prevention in general practice between evidence- and narrative-based medicine:
      squaring the circle?].
AB  - In the German healthcare system, general practitioners (GPs) play an important
      role with regard to individualised prevention, as they are often the first
      contact for patients seeking advice. Additionally, there is a great need for
      preventive counselling from the patient's perspective. However, there is no clear
      evidence for the effectiveness of the prevention programmes established in
      Germany. Future prevention models need to be developed according to evidence
      based criteria. Narrative-based medicine is seen as a promising complementary
      approach to strengthen individualised prevention in primary care. 

PMID- 24889710
TI  - [On the overestimation of the benefit of prevention].
AB  - BACKGROUND: Both pharmacological and non-pharmacological preventive interventions
      can do more harm than good. Health checks target a healthy or symptomless
      population. This is why randomised controlled trials (RCTs) must be conducted to
      provide high-quality evidence for the benefit of an intervention. The present
      article presents examples to demonstrate that the benefit of preventive
      interventions is usually overestimated. METHODS: Standard screening criteria are
      used to critically appraise selected preventive interventions. Screening criteria
      cover the disease, the test, the treatment and the whole programme including
      evaluation and quality assurance. Type-2 diabetes mellitus is used as an example
      to discuss specific criteria for preventive interventions. The current state of
      the evidence is outlined. The article is based primarily on systematic / Cochrane
      reviews of RCTs. RESULTS: A recent Cochrane review including 16 RCTs concluded
      that there is no benefit of general health checks. High-quality evidence on
      individual components of health checks is frequently missing or inconclusive.
      Over the last 30 years reference values for normal blood glucose and normal blood
      pressure as well as treatment targets for patients with type-2 diabetes mellitus
      and hypertension have been repeatedly decreased though this is not supported by
      evidence. Recent high-quality RCTs have shown that these "hit hard and early"
      interventions are detrimental, particularly to those who were the primary target
      group. Consequently, treatment targets have again been raised and recent
      guidelines recommend individualisation of treatment goals taking age and
      comorbidities into account. Important criteria for the implementation of
      preventive interventions are not currently met. With regard to type-2 diabetes
      uncertainties remain as to the clinical significance of pre-diabetes, the
      treatment of pre-diabetes and early treatment of diabetes, the screening tests,
      and target groups. The ADDITION study was unable to prove the benefit of a
      diabetes screening. Intensive lifestyle interventions may result in modest
      reductions of body weight and fewer diabetes diagnoses. However, the clinical
      relevance of the underlying metabolic changes is doubtful or even negligible.
      After almost 10 years, the Look AHEAD study has been terminated early due to the
      ineffectiveness of its intensive lifestyle interventions and the lack of hope
      that the study will succeed in demonstrating any benefit on the primary
      cardiovascular endpoints during the originally planned study period of another 3
      years. CONCLUSION: The benefit of prevention is overestimated whereas harm is
      underestimated. It is most unlikely that medical preventive interventions
      targeting individual behaviour changes will result in better health for our
      population.

PMID- 24889711
TI  - [Comorbidity in medical guidelines: comparison of the current state,
      epidemiologic models and expert opinion].
AB  - INTRODUCTION: Medical guidelines focusing on monomorbidities can be associated
      with adverse events in multimorbid patients. This study investigates how
      comorbidities are actually particularised in a set of German guidelines. In
      addition, it evaluates whether two epidemiologic approaches (disease combinations
      or clusters of comorbidities) can be used to systematically integrate
      multimorbidity in guideline development. METHODS: Based on a matrix of 30
      comorbidities, mentioning of comorbidities in 8 current German guidelines
      (diabetes mellitus, hypertension, heart failure, coronary heart disease, chronic
      obstructive lung disease/asthma, coxarthrosis, low back pain, osteoporosis) was
      investigated. These so called index diseases were selected on the basis of the
      hypothetical case of a multimorbid patient published by Cynthia Boyd and
      colleagues in 2005. Mentioning of comorbidities in the guidelines was compared to
      the epidemiologic approaches of disease combinations and clusters of
      comorbidities. In addition, using the comorbidity matrix, 36 physicians involved
      in everyday care of multimorbid patients assessed whether an explicit
      recommendation for the listed comorbidities would be helpful. RESULTS: Mentioning
      of comorbidities was very heterogeneous across the guidelines investigated,
      ranging from 0 to more than 10. The proportion of the comorbidities that were
      considered relevant by the survey participants ranged from 0 % to 62 % with a
      focus on cardiovascular and metabolic diseases. When using disease combinations,
      only 0 to 3 of the "relevant" comorbidities were identified. Using the cluster
      model may be helpful in identifying whether a particular comorbidity is
      thematically close to the index disease or whether it is associated with an
      interacting thematic area. CONCLUSIONS: Methodological support is needed for
      addressing comorbidities in guidelines in a more consistent way. The currently
      existing epidemiologic approaches should not be used in their current form
      without being further developed and re-evaluated. Expert opinion of physicians
      involved in the care of multimorbid patients should be systematically included in
      methodological refinement studies.

PMID- 24889712
TI  - [Scientability - an answer to homeopathy?].
AB  - Introducing the term "scientability", Christian Weymayr proposed to disapprove of
      clinical studies of homeopathy since the latter contradicts "definite scientific
      findings." This article argues against his conclusion. Specifically, violating
      the principle of total evidence would undermine the credibility of science. 

PMID- 24889713
TI  - Purification of biomass-derived 5-hydroxymethylfurfural and its catalytic
      conversion to 2,5-furandicarboxylic Acid.
AB  - A simple and effective water extraction method is presented for the purification
      5-hydroxylmethylfurfural (HMF) obtained from a biomass dehydration system. Up to
      99% of the HMF can be recovered and the HMF in aqueous solution is directly
      converted to 2,5-furandicarboxylic acid (FDCA) as the sole product. This
      purification technique allows an integrated process to produce FDCA from fructose
      via HMF prepared in an isopropanol monophasic system, with an overall FDCA yield
      of 83% obtained. From Jerusalem raw artichoke biomass to FDCA via HMF prepared in
      a water/MIBK (methyl isobutyl ketone) biphasic system, an overall FDCA yield of
      55% is obtained.

PMID- 24889714
TI  - Ultrasensitive optomechanical magnetometry.
AB  - A cavity optomechanical magneto-meter operating in the 100 pT range is reported.
      The device operates at earth field, achieves tens of megahertz bandwidth with 60
      MUm spatial resolution and microwatt optical-power requirements. These unique
      capabilities may have a broad range of applications including cryogen-free and
      microfluidic magnetic resonance imaging (MRI), and investigation of spin-physics
      in condensed matter systems. 

PMID- 24889715
TI  - Microflotronic arterial tonometry for continuous wearable non-invasive
      hemodynamic monitoring.
AB  - Personalized mobile medicine will continue to advance through the development of
      wearable sensors that can wirelessly provide pertinent health information while
      remaining unobtrusive, comfortable, low cost, and easy to operate and interpret.
      It is the intention that the sensor presented hereafter can contribute to such
      innovation. By applying a combination of emerging microfluidic and electronic
      technologies, a miniature, flexible, transparent, highly sensitive and wearable
      pressure sensor with microfluidic elements has been implemented, referred to as a
      microflotronic device. High sensitivity of 0.1 kPa(-1) and fast response time on
      the order of tens of milliseconds has been achieved on the microflotronic sensor
      design. Its sensitivity is among the highest in impedance-based flexible pressure
      sensors. Once configured into an array, the transparent device can be easily
      aligned over the target artery to measure blood pressure noninvasively and
      continuously. In addition, the ultraflexible and thin plastic construct of the
      microflotronic sensor (of 270 um in height) can be worn comfortably for extended
      periods of time. Importantly, the proposed microflotronic sensor has been
      utilized to perform arterial tonometry with the capability of noninvasive
      monitoring of arterial blood pressure waveforms in a real-time and continuous
      fashion. 

PMID- 24889717
TI  - FEA study on the stress distributions in the polymer coatings of cardiovascular
      drug-eluting stent medical devices.
AB  - Cardiovascular drug-eluting stents (DES) are widely applied medical products to
      treat diseased narrowed arteries. Despite their wide application, there still are
      many clinical adverse effects associated with DES implantation. One of the major
      issues is that the coatings comprised of drug and polymer phases are often
      delaminated during the deployment of the stent, which can lead to more serious
      clinical complications. In the present work, we conducted a 3D finite-element
      analysis (FEA) computational study to quantitatively estimate the stress
      distributions in the coating components of DES devices. To adequately represent
      the skeleton design of modern DES products, we adopted the strut geometry of a
      SYNERGY stent along with a full coating of poly(lactic-co-glycolic) acid. The FEA
      computation results clearly indicate that the curved regions (i.e., kink) are
      subject to much higher stress accumulation in the coating. In addition, it was
      found that the local shear and normal stress distribution profiles in the polymer
      coatings are different from those based on von-Mises stresses near the kink area.

PMID- 24889716
TI  - Rapid antimicrobial susceptibility testing with electrokinetics enhanced
      biosensors for diagnosis of acute bacterial infections.
AB  - Rapid pathogen detection and antimicrobial susceptibility testing (AST) are
      required in diagnosis of acute bacterial infections to determine the appropriate
      antibiotic treatment. Molecular approaches for AST are often based on the
      detection of known antibiotic resistance genes. Phenotypic culture analysis
      requires several days from sample collection to result reporting. Toward rapid
      diagnosis of bacterial infection in non-traditional healthcare settings, we have
      developed a rapid AST approach that combines phenotypic culture of bacterial
      pathogens in physiological samples and electrochemical sensing of bacterial 16S
      rRNA. The assay determines the susceptibility of pathogens by detecting bacterial
      growth under various antibiotic conditions. AC electrokinetic fluid motion and
      Joule heating induced temperature elevation are optimized to enhance the sensor
      signal and minimize the matrix effect, which improve the overall sensitivity of
      the assay. The electrokinetics enhanced biosensor directly detects the bacterial
      pathogens in blood culture without prior purification. Rapid determination of the
      antibiotic resistance profile of Escherichia coli clinical isolates is
      demonstrated. 

PMID- 24889718
TI  - Gastric cancer with para-aortic lymph node metastases: do not miss a chance of
      cure!
AB  - This letter to editor is a comment to the paper by Wang et al. entitled: "A phase
      II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by
      surgery for advanced gastric cancer patients with para-aortic lymph node
      metastasis". In a phase II trial, patients with primary gastric cancer and
      clinical involvement of para-aortic nodes (PAN) were treated by neo-adjuvant
      chemotherapy with capecitabine and oxaliplatin combination, and responders were
      then submitted to gastrectomy with D2 lymphadenectomy. The diagnostic and
      therapeutic approach adopted in this protocol is discussed, with special
      reference to the potential limits of computed tomography scan for the clinical
      diagnosis of PAN metastases (false positive results), and the opportunity to
      perform a D2 plus para-aortic lymphadenectomy, to further increase the chance of
      cure in patients with suspected PAN metastases. 

PMID- 24889720
TI  - A prospective observational study of the prevalence and risk factors for
      colonization by antibiotic resistant bacteria in patients at admission to
      hospital in Singapore.
AB  - BACKGROUND: Drug resistant organisms pose an increasing threat to the successful
      treatment of common infections. Understanding colonization patterns of these
      bacteria is important for effective antibiotic treatment and infection control
      guidelines. METHODS: A prospective observational study was performed to determine
      the prevalence of colonization with extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-E), methicillin-resistant Staphylococcus aureus (MRSA),
      and vancomycin-resistant Enterococcus (VRE) among patients admitted via the
      emergency department to a public tertiary hospital in Singapore. Anterior nares,
      groin, axillary and rectal swabs were collected at admission and cultured using
      standard bacteriological techniques. Clinical data including healthcare contact
      within the past 12 months and recent antibiotic use was collected and analyzed
      using a logistic regression model. RESULTS: 1006 patients were screened. 124
      (12.4%) were colonized by ESBL-E, 18 (1.8%) by MRSA while no VRE was detected.
      Antibiotic use within the past month was the only significant predictor for ESBL
      E colonization in the regression model, with an adjusted odds ratio (AOR) of 2.58
      (1.04 to 6.42). In participants recently prescribed antibiotics and hospitalized
      in the previous 3 months, 29.4% were colonized by ESBL-E. This represented 20.2%
      of the total ESBL-E burden, and ESBL-E was also detected in 6.3% of participants
      with no healthcare contact. Hospitalization and outpatient hospital visits
      predicted MRSA colonization in the univariate analysis. Neither was statistically
      significant in the logistic regression model, with AORs for MRSA colonization
      following hospitalization in the past 3 and 12 months of 3.81 [95% CI 0.84-17.28]
      and 3.48 [0.64-18.92] respectively. CONCLUSION: A high prevalence of colonization
      with ESBL-E was evident among patients at admission, even in the absence of
      recent antibiotic use or contact with healthcare.

PMID- 24889721
TI  - An oral health study of centenarians and children of centenarians.
AB  - OBJECTIVES: To determine whether oral health is better in centenarians than in a
      published birth cohort-matched sample and to compare oral health in centenarian
      offspring with a case-controlled reference sample. DESIGN: Observational cross
      sectional study. SETTING: New England Centenarian Study (NECS). PARTICIPANTS:
      Seventy-three centenarians, 467 offspring, and 251 offspring generation-reference
      cohort subjects from the NECS. MEASUREMENTS: A self-report questionnaire was
      administered to measure oral health in all three groups, with edentulous rate as
      the primary outcome measure. The NECS made information on sociodemographic
      characteristics and medical history available. Centenarian results were compared
      with published birth cohort-matched results. Data from offspring and reference
      cohorts were analyzed to determine differences in oral health and associations
      between oral health measures and specific medical conditions. RESULTS: The
      edentulous rate of centenarians (36.5%) was lower than that of their birth cohort
      (46%) when they were aged 65 to 74 in 1971 to 1974 (according to National Center
      of Health Statistics). Adjusting for confounding factors, the reference cohort
      was more likely to be edentulous (adjusted odds ratio (AOR) = 2.78, 95%
      confidence interval CI = 1.17-6.56), less likely to have all or more than half of
      their own teeth (AOR = 0.48, 95% CI = 0.3-0.76), and less likely to report
      excellent or very good oral health (AOR = 0.65, 95% CI = 0.45-0.94) than the
      centenarian offspring. CONCLUSION: Centenarians and their offspring have better
      oral health than their respective birth cohorts. Oral health may prove to be a
      helpful marker for systemic health and healthy aging.

PMID- 24889722
TI  - The natural history of cerebellar degeneration of Niemann-Pick C mice monitored
      in vitro.
AB  - AIMS: Niemann-Pick type C (NPC) disease is a fatal hereditary lysosomal lipid
      storage disease caused by mutations in NPC1 or NPC2. It is still unknown how this
      disorder evokes clinical signs. Typically, patients develop severe cerebellar
      ataxia due to progressive Purkinje cell loss. Hitherto, in vitro studies did not
      allow monitoring the natural process of NPC-associated Purkinje cell
      degeneration. Aim of this study was to evaluate whether organotypic slice
      cultures are usable to monitor the natural process of NPC-associated Purkinje
      cell degeneration. METHODS: We used organotypic cerebellar slice cultures of a
      well-established NPC mouse model to display the natural history of cerebellar
      degeneration in vitro and cultivated them for a prolonged time period of 6 weeks
      for the first time. Moreover we tested several therapeutic candidates and
      evaluated their effect on Purkinje-cell survival. RESULTS: Our approach proves
      that it is possible to monitor and to prevent NPC-related Purkinje cell death
      reliably in vitro. This is beneficial because in vivo Purkinje cell loss directly
      translates into clinical signs. Thus, therapeutically interesting compounds can
      be tested in vitro, not only to correct biochemical abnormalities, but also to
      show the likelihood of a compound to prevent ataxia. As to be expected from the
      results of previous animal experiments, 2-hydroxypropyl-beta-cyclodextrin rescued
      Purkinje cells. We also discovered that 3-methyladenine preserved Purkinje cell
      numbers by adjusting the autophagic flux in NPC slices. CONCLUSION: We provide
      evidence that cerebellar slice cultures are a powerful in vitro tool to study NPC
      associated Purkinje cell death in an organotypic setting.

PMID- 24889719
TI  - Role of pregnane X receptor in chemotherapeutic treatment.
AB  - Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that
      differently expresses not only in human normal tissues but also in numerous types
      of human cancers. PXR can be activated by many endogenous substances and
      exogenous chemicals, and thus affects chemotherapeutic effects and intervenes
      drug-drug interactions by regulating its target genes involving drug metabolism
      and transportation, cell proliferation and apoptosis, and modulating endobiotic
      homeostasis. Tissue and context-specific regulation of PXR contributes to diverse
      effects in the treatment for numerous cancers. Genetic variants of PXR lead to
      intra- and inter-individual differences in the expression and inducibility of
      PXR, resulting in different responses to chemotherapy in PXR-positive cancers.
      The purpose of this review is to summarize and discuss the role of PXR in the
      metabolism and clearance of anticancer drugs. It is also expected that this
      review will provide insights into PXR-mediated enhancement for chemotherapeutic
      treatment, prediction of drug-drug interactions and personalized medicine. 

PMID- 24889723
TI  - Preliminary study of the fungal ecology at the haematology and medical-oncology
      ward in Bamako, Mali.
AB  - Data on fungal epidemiology in sub-Saharan African countries are scarce. This
      exploratory study aimed to characterize the fungal flora at the Onco-Haematology
      ward of the National Teaching Hospital of Point G in Bamako, Mali. A cross
      sectional survey was conducted in the dry and in the rainy seasons. Nasal swab
      and sputum samples were collected from the hospitalized patients while airborne
      fungal spores were collected using electrostatic dust-fall collectors. Fungi were
      identified by their morphological characteristics and MALDI-TOF mass
      spectrometry. Candida albicans was the most frequent yeast species colonizing
      patients; Aspergillus species were isolated in 86 % of the patients and were the
      main airborne environmental contaminants. Overall, airborne fungal contamination
      rates increased from 33.8 % in the dry to 66.2 % in the rainy season (p < 0.001).
      The most frequent Aspergillus species were Aspergillus niger (36.6 %) and
      Aspergillus flavus (32.92 %). In contrast, Aspergillus fumigatus (5.43 %) was
      relatively rare. This high level of fungal exposure raises concern regarding the
      management of at-risk patients in this Onco-Haematology ward and stresses the
      need for strengthening the mycological diagnostic capacities to accompany the
      implementation of adapted fungal infection prevention and management policies.

PMID- 24889727
TI  - The mediating role of stigmatization in the mental health of adolescent victims
      of sexual violence in Eastern Congo.
AB  - This study aims to explore the factors that explain the mental sequelae of war
      related sexual violence and focuses in particular on the role of stigmatization.
      Drawing on a large-scale quantitative survey undertaken in the war-affected
      region of eastern Democratic Republic of the Congo, we analyze how stigmatization
      mediates the mental health impact of sexual violence on adolescent girls who were
      victims of rape. Twenty-two secondary schools were randomly selected out of a
      stratified sample in Bunia, Eastern Congo. In a cross-sectional, population-based
      survey, 1,305 school-going adolescent girls aged 11-23 completed self-report
      measures assessing war-related traumatic events, experiences of sexual violence,
      stigmatization, and mental health symptoms. Of the 1,305 participants, 38.2%
      (n=499) reported experiences of sexual violence. Victims of sexual violence
      reported more war-related traumatic events and more stigmatization experiences.
      Several hierarchical regression analyses examined the mediating impact of
      stigmatization on the relationship between sexual violence and mental health
      outcomes, thereby controlling for sociodemographics (age, parental availability,
      and socioeconomic status) and war-related traumatic exposure. Our findings show
      that this stigmatization largely explains the mental health impact of sexual
      violence, in particular, on adolescent girls' reported symptoms of depression
      (full mediation) and posttraumatic stress (avoidance and total PTSD: full
      mediation; hyperarousal: partial (40%) mediation). No evidence of mediation by
      stigmatization was found for symptoms of anxiety and intrusion. Stigmatization
      plays thus an important role in shaping the mental sequelae of sexual violence, a
      finding with major consequences for clinical practice. 

PMID- 24889728
TI  - Implementation of differential response: a racial equity analysis.
AB  - Differential response is a growing approach in child welfare that allows for a
      more flexible response to keep children safe by better engaging families. This
      study examined the implementation of Minnesota's approach called Family
      Assessment response, and explored the impact on racial equity outcomes in the
      state's child welfare system. Using logistic regression to analyze administrative
      child welfare data for all screened-in cases between 2003 and 2010 (n=122,095),
      this study explored whether race was a predictor in the following decision
      points: (1) pathway assignment to either Family Assessment (FA) response or a
      traditional investigation (TI); and (2) switching pathway assignment from FA to
      TI. Findings of the analysis indicated that when controlling for poverty and
      other risk factors, African American, Native American and Multiracial children
      were less likely to be assigned to FA compared to Caucasian children for some,
      but not all years in the study timeframe; while Hispanic children were more
      likely to be assigned to FA compared to non-Hispanic children for several years
      in the study timeframe. Disparities around pathway switch from family assessment
      to traditional investigation completely diminished over time. The results of this
      study highlight the importance of applying a racial equity lens in examining new
      policies and practices to ensure equitable implementation for all children and
      families. The findings also emphasize the need for better understanding of the
      unique experiences of Native American and Multiracial children and families, who
      have been under-represented in the research on racial disparities in child
      welfare. 

PMID- 24889729
TI  - Sibling and peer victimization in childhood and adolescence.
AB  - This study examined how victimizations by either a sibling or peer are linked to
      each other and to mental health in childhood and adolescence. The data were from
      the National Survey of Children's Exposure to Violence which includes a sample of
      children aged 3-9 (N=1,536) and adolescents aged 10-17 (N=1,523) gathered through
      telephone interviews. An adult caregiver (usually a parent) provided the
      information for children while self-reports were employed for adolescents.
      Fifteen percent of each age group reported victimization by both a sibling and
      peer. Victimization by a sibling alone was more common in childhood than
      adolescence. Victimization by a sibling was predictive of peer victimization.
      Children and adolescents victimized by both a sibling and peer reported the
      greatest mental distress. This work establishes that for some children and
      adolescents, victimization at the hands of other juveniles happens both at home
      and school. Programs should consider the role of siblings and target parents and
      siblings to encourage the development and maintenance of constructive sibling
      interactions. 

PMID- 24889730
TI  - Heterogeneous solution NMR signal amplification by reversible exchange.
AB  - A novel variant of an iridium-based organometallic catalyst was synthesized and
      used to enhance the NMR signals of pyridine in a heterogeneous phase by
      immobilization on polymer microbead solid supports. Upon administration of
      parahydrogen (pH2) gas to a methanol mixture containing the HET-SABRE catalyst
      particles and the pyridine, up to fivefold enhancements were observed in the (1)H
      NMR spectra after sample transfer to high field (9.4 T). Importantly,
      enhancements were not due to any residual catalyst molecules in solution, thus
      supporting the true heterogeneity of the SABRE process. Further significant
      improvements may be expected by systematic optimization of experimental
      parameters. Moreover, the heterogeneous catalyst is easy to separate and recycle,
      thus opening a door to future potential applications varying from spectroscopic
      studies of catalysis, to imaging metabolites in the body without concern of
      contamination from expensive and potentially toxic metal catalysts or
      accompanying organic molecules.

PMID- 24889731
TI  - Different effects of two dipeptidyl peptidase-4 inhibitors and glimepiride on
      beta-cell function in a newly designed two-step hyperglycemic clamp.
AB  - BACKGROUND: Dipeptidyl peptidase (DPP)-4 inhibitors and sulfonylureas may have
      different effects on islet function. We designed a new two-step hyperglycemic
      clamp to further compare the effects of sitagliptin, saxagliptin, and glimepiride
      on beta-cell function and the incretin effect. METHODS: The present study was a
      four-way cross-over open label randomized study. Twelve healthy male subjects
      were administered a single dose of sitagliptin (100 mg), saxagliptin (5 mg),
      glimepiride (2 mg) or blank control 2 h before undergoing a two-step
      hyperglycemic clamp (Step 1: only intravenous glucose was administered; Step 2:
      i.v. glucose loading was combined with oral glucose consumption). Two-phase
      insulin secretion, glucagon secretion, and incretin levels were measured during
      the clamp. RESULTS: In Step 1, with i.v. glucose only, there were no differences
      between the effects of the three drugs on insulin secretion, except that
      saxagliptin increased second-phase insulin secretion more than glimepiride (P =
      0.007). In Step 2, oral glucose consumption led to an approximate two fold
      increase in insulin secretion and both gliptins significantly increased first
      phase insulin secretion compared with glimepiride (P = 0.003 for both).
      Saxagliptin further increased second-phase insulin secretion compared with
      glimepiride (P = 0.005) and sitagliptin (P < 0.001). Both gliptins significantly
      decreased glucagon secretion and increased active glucagon-like peptide-1 (GLP-1)
      compared with glimepiride, especially in Step 2. CONCLUSIONS: The two-step
      hyperglycemic clamp appears to be a precise method to assess beta-cell function
      by taking the effect of incretins into consideration. The oral glucose
      consumption adds to the i.v. glucose infusion, amplifying the differences in the
      effects of DPP-4 inhibitors and glimepiride on insulin secretion.

PMID- 24889732
TI  - Developing ways to evaluate in the laboratory how inhalation devices will be used
      by patients and care-givers: the need for clinically appropriate testing.
AB  - The design of methods in the pharmaceutical compendia for the laboratory-based
      evaluation of orally inhaled product (OIP) performance is intentionally aimed for
      simplicity and robustness in order to achieve the high degree of accuracy and
      precision required for the assurance of product quality in a regulated
      environment. Consequently, performance of the inhaler when used or even misused
      by the patient or care-giver has often not been assessed. Indeed, patient-use
      based methodology has been developed in a somewhat piecemeal basis when a need
      has been perceived by the developing organization. There is, therefore, a lack of
      in-use test standardization across OIP platforms, and often important details
      have remained undisclosed beyond the sponsoring organization. The advent of
      international standards, such as ISO 20072:2009, that focus specifically on the
      OIP development process, together with the need to make these drug delivery
      devices more patient-friendly as an aid to improving compliance, is necessitating
      that clinically appropriate test procedures be standardized at the OIP class
      level. It is also important that their capabilities and limitations are well
      understood by stakeholders involved in the process. This article outlines how
      this process might take place, drawing on current examples in which significant
      advances in methodology have been achieved. Ideally, it is hoped that such
      procedures, once appropriately validated, might eventually become incorporated
      into the pharmacopeial literature as a resource for future inhaler developers,
      regulatory agencies, and clinicians seeking to understand how these devices will
      perform in use to augment ongoing product quality testing which is adequately
      served by existing methods. 

PMID- 24889733
TI  - Encapsulation of sorbitan ester-based organogels in alginate microparticles.
AB  - Leaching of the internal apolar phase from the biopolymeric microparticles during
      storage is a great concern as it undoes the beneficial effects of encapsulation.
      In this paper, a novel formulation was prepared by encapsulating the sunflower
      oil-based organogels in alginate microparticles. Salicylic acid and metronidazole
      were used as the model drugs. The microparticles were prepared by double emulsion
      methodology. Physico-chemical characterization of the microparticles was done by
      microscopy, FTIR, XRD, and DSC studies. Oil leaching studies, biocompatibility,
      mucoadhesivity, in vitro drug release, and the antimicrobial efficiency of the
      microparticles were also performed. The microparticles were found to be spherical
      in shape. Gelation of the sunflower oil prevented leaching of the internal phase
      from the microparticles. Release of drugs from the microparticles followed
      Fickian kinetics and non-Fickian kinetics in gastric and intestinal environments,
      respectively. Microparticles showed good antimicrobial activity against both Gram
      positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria. The
      results suggested that the developed formulations hold promise to carry oils
      without leakage of the internal phase. Encapsulation of organogels within the
      microparticles has improved the drug entrapment efficiency and improved
      characteristics for controlled delivery applications. 

PMID- 24889734
TI  - Increasing doxycycline hyclate photostability by complexation with beta
      cyclodextrin.
AB  - Doxycycline hyclate (DOX) is a highly photosensitive drug, a feature that limits
      the stability of the corresponding dosage forms. The main objectives of this work
      were the preparation and characterization of an inclusion complex of DOX with
      beta-cyclodextrin (betaCD) and to investigate if this approach could improve the
      photostability of the drug. Guest-host interactions were investigated using
      nuclear magnetic resonance, which were afterwards combined with molecular
      modeling methods to study the complex formation and its three-dimensional
      structure was proposed. A freeze-drying method was applied to obtain the complex
      in the solid state, which was further confirmed by thermal and spectroscopic
      techniques. To evaluate the complexation effect on DOX integrity, the
      photostability of the inclusion complex was studied, with a significant decrease
      in the photodegradation of DOX being found in aqueous solution upon complexation.
      Finally, the photoprotection produced by the complexation was evaluated by means
      of an antimicrobial assay. Overall, the presented results suggest that the
      formulation of DOX complexed with betaCD constitutes an interesting approach for
      the preparation of pharmaceutical dosage forms of DOX with enhanced stability
      properties. 

PMID- 24889736
TI  - Aerosol performance and long-term stability of surfactant-associated liposomal
      ciprofloxacin formulations with modified encapsulation and release properties.
AB  - Previously, we showed that the encapsulation and release properties of a
      liposomal ciprofloxacin formulation could be modified post manufacture, by
      addition of surfactant in concert with osmotic swelling of the liposomes. This
      strategy may provide more flexibility and convenience than the alternative of
      manufacturing multiple batches of liposomes differing in composition to cover a
      wide range of release profiles. The goal of this study was to develop a
      surfactant-associated liposomal ciprofloxacin (CFI) formulation possessing good
      long-term stability which could be delivered as an inhaled aerosol. Preparations
      of 12.5 mg/ml CFI containing 0.4% polysorbate 20 were formulated between pH 4.7
      and 5.5. These formulations, before and after mesh nebulization, and after
      refrigerated storage for up to 2 years, were characterized in terms of liposome
      structure by cryogenic transmission electron microscopy (cryo-TEM) imaging,
      vesicle size by dynamic light scattering, pH, drug encapsulation by
      centrifugation-filtration, and in vitro release (IVR) performance. Within the
      narrower pH range of 4.9 to 5.2, these formulations retained their
      physicochemical stability after 2-year refrigerated storage, were robust to mesh
      nebulization, and formed respirable aerosols with a volume mean diameter (VMD) of
      3.7 MUm and a geometric standard deviation (GSD) of 1.7. This study demonstrates
      that it may be possible to provide a range of release profiles by simple addition
      of surfactant to a liposomal formulation post manufacture, and that these
      formulations may retain their physicochemical properties after long-term
      refrigerated storage and following aerosolization by mesh nebulizer. 

PMID- 24889735
TI  - Inter-grade and inter-batch variability of sodium alginate used in alginate-based
      matrix tablets.
AB  - The purpose of this study is to characterize the inter-grade and inter-batch
      variability of sodium alginate used in the formulation of matrix tablets. Four
      different grades and three batches of one grade of sodium alginate were used to
      prepare matrix tablets. Swelling, erosion, and drug release tests of sodium
      alginate matrix tablets were conducted in a USP dissolution apparatus.
      Substantial differences in swelling and erosion behavior of sodium alginate
      matrix tablets were evident among different viscosity grades. Even different
      batches of the same grade exhibit substantial differences in the swelling and
      erosion behavior of their matrix tablets. The erosion behavior of sodium alginate
      matrix tablets can be partly explained by their rheological properties (both
      apparent viscosity and viscoelasticity) in solution. Sodium alginate with higher
      apparent viscosity and viscoelasticity in solution show slower erosion rate and
      higher swelling rate. Compacts prepared from grades or batches with higher
      viscosity and higher viscoelasticity show slower drug release. For grades or
      batches with similar apparent viscosities, apparent viscosities of sodium
      alginate solution at low concentration alone are not sufficient to predict the
      functionality of sodium alginate in matrix tablets. Viscoelastic properties of
      sodium alginate solutions at one high concentration corresponding to the polymer
      gel state, may be suitable indicia of the extended release behavior of sodium
      alginate matrix tablets. 

PMID- 24889737
TI  - Mutations and thrombosis in essential thrombocythemia: prognostic interaction
      with age and thrombosis history.
AB  - BACKGROUND: Vascular events in essential thrombocythemia (ET) are associated with
      advanced age and thrombosis history. Recent information suggests additional
      effect from the presence of specific mutations. OBJECTIVES: To examine the
      influence of age and thrombosis history on the reported association between
      mutational status and thrombosis-free survival in ET. PATIENTS AND METHODS:
      Analysis was performed using a Mayo Clinic cohort of 300 ET patients, and key
      findings were reanalyzed by including additional 102 Italian patients. RESULTS:
      Among 300 Mayo patients with ET (median age 55 yr, 60% females), mutational
      frequencies were 53% JAK2, 32% CALR, 3% MPL, and 12% JAK2, CALR and MPL wild
      type. One hundred and six (35%) patients experienced arterial (n = 75) or venous
      (n = 43) events, before (n = 55) or after (n = 71) diagnosis. In univariate
      analysis, compared to JAK2-mutated cases, JAK2, CALR and MPL wild type (HR 0.31,
      95% CI 0.11-0.86), and CALR-mutated (0.53, 95% CI 0.30-0.92) patients displayed
      better thrombosis-free survival. JAK2, CALR, and MPL wild type remained
      significant (P = 0.03; HR 0.32, 95% CI 0.11-0.9) during multivariable analysis
      that included age (P = 0.01) and thrombosis history (P = 0.0006); a favorable
      impact from CALR mutations was of borderline significance (P = 0.1; HR 0.62, 95%
      CI 0.35-1.1), but became significant (P = 0.02) when multivariable analysis
      including thrombosis history (P = 0.02) was performed on patients younger than 60
      yr of age. CONCLUSIONS: The favorable impact of mutational status on thrombosis
      free survival in ET might be most evident for JAK2, CALR, and MPL wild type
      patients, whereas the favorable effect from CALR mutations might be confined to
      young patients.

PMID- 24889738
TI  - Hirsutism: an evidence-based treatment update.
AB  - BACKGROUND: Hirsutism has a relatively high prevalence among women. Depending
      upon societal and ethnic norms, it can cause significant psychosocial distress.
      Importantly, hirsutism may be associated with underlying disorders and co
      morbidities. Hirsutism should not simply be looked upon as an issue of cosmesis.
      Patients require appropriate evaluation so that underlying etiologies and
      associated sequelae are recognized and managed. Treatment of hirsutism often
      requires a multidisciplinary approach, and a variety of physical or pharmacologic
      modalities can be employed. Efficacy of these therapies is varied and depends,
      among other things, upon patient factors including the underlying etiology,
      hormonal drive, and local tissue sensitivity to androgens. OBJECTIVE: The
      objective of this paper is to review and summarize current evidence evaluating
      the efficacy of various treatment modalities for hirsutism in premenopausal
      women. METHODS: Online databases were searched to identify all relevant prior
      systematic reviews and meta-analyses as well as recently published (2012-present)
      randomized controlled trials (RCTs) on hirsutism treatment. RESULTS: Four
      recently published RCTs met criteria for inclusion in our review. In addition,
      one meta-analysis and one systematic review/treatment guideline were identified
      in the recent literature. Physical modalities and oral contraceptive pills (OCPs)
      remain first-line treatments. Evidence supports the use of electrolysis for
      permanent hair removal in localized areas and lasers (particularly alexandrite
      and diode lasers) for permanent hair reduction. Topical eflornithine can be used
      as monotherapy for mild hirsutism and as an adjunct therapy with lasers or
      pharmacotherapy in more severe cases. Combined OCPs as a class are superior to
      placebo; however, antiandrogenic and low-dose neutral OCPs may be slightly more
      efficacious in improving hirsutism compared with other types of OCPs.
      Antiandrogens are indicated for moderate to severe hirsutism, with spironolactone
      being the first-line antiandrogen and finasteride and cyproterone acetate being
      second-line antiandrogens. Due to its risk for hepatotoxicity, flutamide is not
      considered a first-line therapy. If used, the lowest effective dose should be
      administered with careful monitoring of liver enzymes. Monotherapy with an
      insulin sensitizer does not significantly improve hirsutism. While insulin
      sensitizers improve important metabolic and endocrine aberrations in polycystic
      ovary syndrome, they are not recommended when hirsutism is the sole indication
      for use. Lifestyle modification counseling is recommended. Gonadotropin-releasing
      hormone analogs and glucocorticoids are only recommended in specific
      circumstances. Additional therapies without sufficient supportive evidence of
      efficacy are ovarian surgery, statins (HMG-CoA reductase inhibitors), and vitamin
      D supplementation. LIMITATIONS: In general, most therapies garner recommendations
      that are weak (where the estimates of benefits versus risks of therapy are either
      closely balanced or uncertain) and are based on low- to moderate-quality
      evidence. CONCLUSIONS: Risks and benefits of treatment must be carefully
      considered and discussed with the patient. Expectations for efficacy should be
      appropriately set. A minimum of 6 months is required to see benefit from
      pharmacotherapy and lifelong treatment is often necessary for sustained benefit.

PMID- 24889739
TI  - Epstein-Barr virus viral load and serology in childhood non-Hodgkin's lymphoma
      and chronic inflammatory conditions in Uganda: implications for disease risk and
      characteristics.
AB  - Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory
      conditions. In this study, EBV detection was compared in children with non
      Hodgkin's lymphoma and children with chronic inflammatory conditions, using
      samples and data from a case-control study carried out at the Mulago National
      Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva,
      whole blood and white blood cells by real-time PCR. Serological values for IgG
      VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic
      inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non
      Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals
      (CIs) were calculated. Of the 127 children included (87 males and 40 females;
      median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's
      lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory
      conditions, and only 10% were HIV-positive. The most common clinical
      presentations for all disease categories considered were fever, night sweats, and
      weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma
      compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value =
      0.04), but EBV viral loads in saliva and white blood cells were not different in
      any of the disease categories considered. A significant difference in EAd-IgG was
      observed when non-Hodgkin's lymphoma was compared with chronic inflammatory
      conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to
      chronic inflammatory conditions, EBV viral load was elevated in Burkitt's
      lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an
      association between virological and serological markers of EBV and childhood non
      Hodgkin's lymphoma, irrespective of subtype, in Uganda.

PMID- 24889740
TI  - Hepatitis C virus treatment revolution: need for close monitoring.

PMID- 24889741
TI  - Temporal and spatial temperature measurement in insulator-based dielectrophoretic
      devices.
AB  - Insulator-based dielectrophoresis is a relatively new analytical technique with a
      large potential for a number of applications, such as sorting, separation,
      purification, fractionation, and preconcentration. The application of insulator
      based dielectrophoresis (iDEP) for biological samples, however, requires the
      precise control of the microenvironment with temporal and spatial resolution.
      Temperature variations during an iDEP experiment are a critical aspect in iDEP
      since Joule heating could lead to various detrimental effects hampering
      reproducibility. Additionally, Joule heating can potentially induce thermal flow
      and more importantly can degrade biomolecules and other biological species. Here,
      we investigate temperature variations in iDEP devices experimentally employing
      the thermosensitive dye Rhodamin B (RhB) and compare the measured results with
      numerical simulations. We performed the temperature measurement experiments at a
      relevant buffer conductivity range commonly used for iDEP applications under
      applied electric potentials. To this aim, we employed an in-channel measurement
      method and an alternative method employing a thin film located slightly below the
      iDEP channel. We found that the temperature does not deviate significantly from
      room temperature at 100 MUS/cm up to 3000 V applied such as in protein iDEP
      experiments. At a conductivity of 300 MUS/cm, such as previously used for
      mitochondria iDEP experiments at 3000 V, the temperature never exceeds 34 
      degrees C. This observation suggests that temperature effects for iDEP of
      proteins and mitochondria under these conditions are marginal. However, at larger
      conductivities (1 mS/cm) and only at 3000 V applied, temperature increases were
      significant, reaching a regime in which degradation is likely to occur. Moreover,
      the thin layer method resulted in lower temperature enhancement which was also
      confirmed with numerical simulations. We thus conclude that the thin film method
      is preferable providing closer agreement with numerical simulations and further
      since it does not depend on the iDEP channel material. Overall, our study
      provides a thorough comparison of two experimental techniques for direct
      temperature measurement, which can be adapted to a variety of iDEP applications
      in the future. The good agreement between simulation and experiment will also
      allow one to assess temperature variations for iDEP devices prior to experiments.

PMID- 24889742
TI  - PsMPK7, a stress-associated mitogen-activated protein kinase (MAPK) in
      Phytophthora sojae, is required for stress tolerance, reactive oxygenated species
      detoxification, cyst germination, sexual reproduction and infection of soybean.
AB  - The sensing of stress signals and their transduction into appropriate responses
      are crucial for the adaptation, survival and infection of phytopathogenic fungi
      and oomycetes. Amongst evolutionarily conserved pathways, mitogen-activated
      protein kinase (MAPK) cascades function as key signal transducers that use
      phosphorylation to convey information. In this study, we identified a gene,
      designated PsMPK7, one of 14 predicted genes encoding MAPKs in Phytophthora
      sojae. PsMPK7 was highly transcribed in each tested stage, but was up-regulated
      in the zoospore, cyst and cyst germination stages. Silencing of PsMPK7 affected
      the growth of germinated cysts, oospore production and the pathogenicity of
      soybean. PsMPK7 transcription was induced by stresses from sorbitol, NaCl and
      hydrogen peroxide. Transformants in which PsMPK7 expression was silenced (PsMPK7
      silenced) were significantly more sensitive to osmotic and oxidative stress.
      Aniline blue and diaminobenzidine staining revealed that the silenced lines did
      not suppress the host reactive oxygen species (ROS) burst, indicating that either
      the inoculated plants activated stronger defence responses to the transformants
      and/or the PsMPK7-silenced transformants failed to overcome plant defences. In
      addition, extracellular secretion of laccase decreased in the silenced lines.
      Overall, our results indicate that the PsMPK7 gene encodes a stress-associated
      MAPK in P. sojae that is important not only for responses to various stresses,
      but also for ROS detoxification, cyst germination, sexual oospore production and
      infection of soybean. 

PMID- 24889743
TI  - Community-level assessment of dental plaque bacteria susceptibility to triclosan
      over 19 years.
AB  - BACKGROUND: Triclosan is a broad-spectrum antimicrobial agent used in toothpaste
      to reduce dental plaque, gingivitis and oral malodor. This community-level
      assessment evaluated the susceptibility of dental plaque bacteria to triclosan in
      samples collected over 19 years. METHODS: A total of 155 dental plaque samples
      were collected at eleven different times over 19 years from 58 adults using 0.3%
      triclosan, 2% copolymer, 0.243% sodium fluoride toothpaste and from 97 adults
      using toothpaste without triclosan. These included samples from 21 subjects who
      used triclosan toothpaste for at least five years and samples from 20 control
      subjects. The samples were cultured on media containing 0, 7.5 or 25 MUg/ml
      triclosan. Descriptive statistics and p values were computed and a linear
      regression model and the runs test were used to examine susceptibility over time.
      RESULTS: Growth inhibition averaged 99.451% (91.209 - 99.830%) on media
      containing 7.5 MUg/ml triclosan and 99.989% (99.670 - 100%) on media containing
      25 MUg/ml triclosan. There was no change in microbial susceptibility to triclosan
      over time discernible by regression analysis or the runs test in plaque samples
      taken over 19 years including samples from subjects using a triclosan-containing
      dentifrice for at least five years. CONCLUSIONS: This community-level assessment
      of microbial susceptibility to triclosan among supragingival plaque bacteria is
      consistent with the long-term safety of a 0.3% triclosan, 2% copolymer, 0.243%
      sodium fluoride dentifrice.

PMID- 24889744
TI  - Identification of 1, 4-Dihydrothieno [3', 2':5, 6]thiopyrano[4, 3-c] pyrazole
      derivatives as human 5-Lipo-oxygenase inhibitors.
AB  - A series of novel 1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]-pyrazole-3
      carboxamide derivatives were synthesized and evaluated for their inhibitory
      activity to human 5-lipo-oxygenase (5-LOX). Compound 7c was found to exhibit
      significant inhibition to human 5-LOX with IC50 value of 5.7 +/- 0.9 MUm.
      Compound 7c was further studied using molecular docking in order to delineate its
      structure-activity relationship and to gain insight into the design of effective
      5-LOX inhibitors.

PMID- 24889745
TI  - Novel aspinolide production by Trichoderma arundinaceum with a potential role in
      Botrytis cinerea antagonistic activity and plant defence priming.
AB  - Harzianum A (HA), a trichothecene produced by Trichoderma arundinaceum, has
      recently been described to have antagonistic activity against fungal plant
      pathogens and to induce plant defence genes. In the present work, we have shown
      that a tri5 gene-disrupted mutant that lacks HA production overproduces two
      polyketides, aspinolides B and C, which were not detected in the wild-type
      strain. Furthermore, four new aspinolides (D-G) were characterized. These
      compounds confirm that a terpene-polyketide cross-pathway exists in T.
      arundinaceum, and they may be responsible for the antifungal activity and the
      plant sensitization effect observed with the tri5-disrupted mutant. In addition,
      the molecular changes involving virulence factors in the phytopathogenic fungus
      Botrytis cinerea 98 (Bc98) during interaction with T. arundinaceum were
      investigated. The expression of genes involved in the production of botrydial by
      Bc98 was relatively repressed by HA, whereas other virulence genes of this
      pathogen were induced by the presence of T. arundinaceum, for example atrB and
      pg1 which encode for an ABC transporter and endopolygalacturonase 1 respectively.
      In addition, the interaction with Bc98 significantly repressed the production of
      HA by T. arundinaceum, indicating that a bidirectional transcriptional regulation
      is established between these two antagonistic fungi. 

PMID- 24889746
TI  - [Vitamin D, vascular risk, and mortality in alcoholic patients].

PMID- 24889747
TI  - [Crystalline miliaria].

PMID- 24889748
TI  - [Oral anticoagulation in chronic kidney disease with atrial fibrillation].
AB  - Atrial fibrillation is a common finding in patients with chronic kidney disease
      (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED
      scales, used in the general population to assess the risk/benefit of oral
      anticoagulation (OAC), underestimate respectively the risk of embolism and
      haemorrhage in CKD, making it difficult to decide whether to use OAC or not.
      Based on the available evidence, it seems indicated to use OAC in stage 3 CKD,
      while it is controversial in advanced stages. New OAC such as dabigatran and
      rivaroxaban have been approved in stage 3 CKD but their role is still somewhat
      uncertain. 

PMID- 24889749
TI  - [C5-carnitine false positive results in newborn screening: what is the cause?].

PMID- 24889750
TI  - [The relevance of the ankle-arm index to the reclassification of cardiovascular
      risk in asymptomatic hypertensive middle-aged males].
AB  - BACKGROUND AND OBJECTIVE: The ankle-brachial index allows for the detection of
      subclinical cardiovascular disease and risk, by diagnosing peripheral arterial
      disease and arterial calcification. Asymptomatic hypertensive men, between 45-55
      years and with the suspicion of low risk, could be an important population group
      to benefit from this technique. The aim of the study was to compare the frequency
      of abnormal ankle-brachial index (subclinical peripheral arterial disease and
      arterial calcification) between asymptomatic hypertensive and non-hypertensive
      men, of the same age and suspicion of low risk. PATIENTS AND METHODS: Two hundred
      and forty-four asymptomatic men (122 hypertensive and 122 non-hypertensive),
      between 45 and 55 years and an REGICOR index<10, were voluntarily recruited using
      consecutive sampling. Complete anamnesis, physical examination, laboratory tests
      and ankle-brachial index determination were carried out on all patients. RESULTS:
      We detected abnormal ankle-brachial index values in 9.8% (12 cases) of the
      hypertensive subjects and in 1.6% (2 cases) of non-hypertensive subjects
      (P=.006). In the multivariate analysis, hypertension was significantly associated
      with an abnormal ankle-brachial index (P<.026) (odds ratio [OR] 5.9, 95%
      confidence interval [95% CI] 1.2-28.3), smoking (P=.018) (OR 2.7; 95% CI 1.2-6.2)
      and abdominal obesity (P=.005) (OR 2.8; 95% CI 1.3-5.9). CONCLUSIONS: The
      population group analyzed in this study might be considered as an overriding
      segment for detecting subclinical cardiovascular disease and risk with the ankle
      brachial index. Further studies are needed to establish the prevalence of
      abnormal ankle-brachial index in this population in order to assess its
      efficiency.

PMID- 24889751
TI  - Update on evidence-based reviews with recommendations in adult chronic
      rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) has a significant impact not only on individuals who
      are afflicted but also on society as a whole. An increasing emphasis is being
      placed on incorporating the best available evidence into the care of patients, in
      association with an individual clinician's expertise and the patient's values.
      Recent evidence-based reviews with recommendations (EBRRs) have distilled our
      knowledge of CRS treatment options and have also pointed out continued gaps in
      this knowledge. This review synthesizes the findings of 8 EBRRs regarding CRS
      published in the International Forum of Allergy and Rhinology between 2011 and
      2014. The recommendations in this review are based on the best available evidence
      and are meant to be incorporated into each patient's individual care, along with
      the practitioner's expertise and the individual patient's values and
      expectations. It is hoped that the EBRRs, and the process that spawned them, can
      provide the foundation for future guidelines in the diagnosis and management of
      CRS.

PMID- 24889752
TI  - Rapidly improved determination of metabolites from biological data sets using the
      high-efficient TransOmics tool.
AB  - Metabolomics is a new approach based on the systematic study of the full
      complement of metabolites in a biological sample. Extracting biomedical
      information from large datasets is of considerable complexity. Furthermore, the
      traditional method of assessing metabolomics data is not only time-consuming but
      it is often subjective work. Here we used sensitive ultra-performance LC-ESI/Q
      TOF high-definition mass spectrometry (UPLC-ESI-Q-TOF-MS) in positive ion mode
      coupled with a new developed software program TransOmics for widely untargeted
      metabolomics, which incorporates novel nonlinear alignment, deconvolution,
      matched filtration, peak detection, and peak matching to characterize metabolites
      as a case study. The TransOmics method can facilitate prioritization of the data
      and greatly increase the probability of identifying metabolites related to the
      phenotype of interest. By this means, 17 urinary differential metabolites were
      identified (less than 10 min) involving the key metabolic pathways including
      tyrosine metabolism, glutathione metabolism, phenylalanine metabolism, ascorbate
      and aldarate metabolism, arginine and proline metabolism, and so forth.
      Metabolite identification has also been significantly improved, using the
      correlation peak patterns in contrast to a reference metabolite panel. It can
      detect and identify metabolites automatically and remove background noise, and
      also provides a user-friendly graphical interface to apply principal component
      analyses, correlation analysis and compound statistics. This investigation
      illustrates that metabolomics combined with the proposed bioinformatic approach
      (based on TransOmics) is important to elucidate the developing biomarkers and the
      physiological mechanism of disease, and has opened the door for the development
      of a new genre of metabolite identification methods. 

PMID- 24889753
TI  - Hepatitis activity should be considered a confounder of liver stiffness measured
      with MR elastography.
AB  - PURPOSE: To evaluate the effect of hepatitis activity on liver stiffness
      measurements and the role of serum alanine aminotransferase (ALT) in liver
      fibrosis staging by MR elastography (MRE). MATERIALS AND METHODS: We measured
      liver stiffness (kPa) in 135 patients by MRE and histologically assessed fibrosis
      and hepatitis activity within 2 months. Stepwise multiple linear regression was
      performed to determine the maximum adjusted R(2) against liver stiffness, after
      adjusting for nothing (model 1), ALT/upper limit of normal categories (model 2),
      and hepatitis activity (A grade) by METAVIR (model 3). Logistic regression was
      used to identify independent factors associated with pathologically proven
      cirrhosis. RESULTS: Platelet count and METAVIR F score were strongly associated
      with liver stiffness. The adjusted R(2) value of model 3 (0.7026) was higher than
      those of models 1 (0.6472) and 2 (0.6564), showing that hepatitis activity
      affected liver stiffness measurement. High ALT levels (odds ratio, 0.0066; P =
      0.0003) as well as MRE (odds ratio, 9.91; P < 0.0001) were independently
      associated with cirrhosis. CONCLUSION: Hepatitis activity may be a confounder of
      liver stiffness measurement during liver fibrosis staging using MRE. MRE can
      potentially make an overdiagnosis of liver cirrhosis if the patient has high ALT
      levels.

PMID- 24889755
TI  - Method of treating patients with acute type A aortic dissection and lower
      extremity malperfusion.
AB  - The management of an acute type A aortic dissection in the setting of peripheral
      vascular malperfusion is not well defined. Several institutions proceed with
      initial percutaneous intervention to restore end organ perfusion, followed by
      delayed operative repair of the type A dissection. This strategy is associated
      with high mortality rates from aortic rupture, myocardial infarction, and stroke.
      We describe a technique, where acute limb ischemia is concomitantly managed with
      the replacement of the ascending aorta/hemiarch or aortic arch. In addition to
      axillary artery cannulation, the ischemic lower extremity is perfused through a
      polytetrafluoroethylene (PTFE) graft, which is connected to the cardiopulmonary
      bypass (CPB) circuit.

PMID- 24889754
TI  - Optimization of white-matter-nulled magnetization prepared rapid gradient echo
      (MP-RAGE) imaging.
AB  - PURPOSE: To optimize the white-matter-nulled (WMn) Magnetization Prepared Rapid
      Gradient Echo (MP-RAGE) sequence at 7 Tesla (T), with comparisons to 3T. METHODS:
      Optimal parameters for maximizing signal-to-noise ratio (SNR) efficiency were
      derived. The effect of flip angle and repetition time (TR) on image blurring was
      modeled using simulations and validated in vivo. A novel two-dimensional (2D) 
      centric radial fan beam (RFB) k-space segmentation scheme was used to shorten
      scan times and improve parallel imaging. Healthy subjects as well as patients
      with multiple sclerosis and tremor were scanned using the optimized protocols.
      RESULTS: Inversion repetition times (TS) of 4.5 s and 6 s were found to yield the
      highest SNR efficiency for WMn MP-RAGE at 3T and 7T, respectively. Blurring was
      more sensitive to flip in WMn than in CSFn MP-RAGE and relatively insensitive to
      TR for both regimes. The 2D RFB scheme had 19% and 47% higher thalamic SNR and
      SNR efficiency than the 1D centric scheme for WMn MP-RAGE. Compared with 3T, SNR
      and SNR efficiency were higher for the 7T WMn regime by 56% and 41%,
      respectively. MS lesions in the cortex and thalamus as well as thalamic subnuclei
      in tremor patients were clearly delineated using WMn MP-RAGE. CONCLUSION:
      Optimization and new view ordering enabled MP-RAGE imaging with 0.8-1 mm(3)
      isotropic spatial resolution in scan times of 5 min with whole brain coverage.

PMID- 24889757
TI  - Oral cancer in Australia 1982-2008: a growing need for opportunistic screening
      and prevention.
AB  - BACKGROUND: Globally, a decline in the incidence of oral cancer has been noted,
      while the mortality rates have remained relatively stable. The aim of this study
      was to provide an update on the incidence and mortality of oral cancer in
      Australia on a national and state level. METHODS: Data regarding new cases and
      deaths associated with cancer of the lip, oral cavity and oropharynx were
      obtained from the Australian Institute of Health and Welfare for the period 1982
      2008. Crude- and age-standardized incidence and mortality rates were calculated
      for all of Australia and for each state and territory. RESULTS: A total of 60 826
      cases of lip, oral cavity and oropharyngeal cancer were diagnosed in Australia.
      Between 1992 and 2008, a decline in the annual percentage change of age
      standardized incidence was noted. The lip, followed by the tongue, continue to
      represent the most common sites of new oral cancer cases. There was no
      significant change in the rates of mortality for oral cancer over the time
      period. CONCLUSIONS: These findings show that the oral cancer mortality rate
      remains high despite a decline in incidence over the past three decades,
      highlighting a greater need for dental practitioners to undertake preventive
      strategies and opportunistic screening for patients.

PMID- 24889756
TI  - Preliminary investigation of the influence of dopamine regulating genes on social
      working memory.
AB  - Working memory (WM) refers to mental processes that enable temporary retention
      and manipulation of information, including information about other people
      ("social working memory"). Previous studies have demonstrated that nonsocial WM
      is supported by dopamine neurotransmission. Here, we investigated in 131 healthy
      adults whether dopamine is similarly involved in social WM by testing whether
      social and nonsocial WM are influenced by genetic variants in three genes coding
      for molecules regulating the availability of dopamine in the brain: catechol-O
      methyltransferase (COMT), dopamine active transporter (DAT), and monoamine
      oxidase A (MAOA). An advantage for the Met allele of COMT was observed in the two
      standard WM tasks and in the social WM task. However, the influence of COMT on
      social WM performance was not accounted for by its influence on either standard
      WM paradigms. There was no main effect of DAT1 or MAOA, but a significant COMT x
      DAT1 interaction on social WM performance. This study provides novel preliminary
      evidence of effects of genetic variants of the dopamine neurotransmitter system
      on social cognition. The results further suggest that the effects observed on
      standard WM do not explain the genetic effects on effortful social cognition. 

PMID- 24889759
TI  - Urea-induced acid amplification: a new approach for metal-free insertion
      chemistry.
AB  - The enhanced catalytic activity of difluoroboronate ureas proved to be essential
      as an acidity amplifier to promote metal-free O-H and S-H insertion reactions of
      alpha-aryldiazoacetates in high yield. This methodology was found to be generally
      applicable to a broad substrate scope and presents a conceptually new approach
      for organocatalytic diazo insertion reactions. Mechanistic investigations suggest
      that the reaction pathway involves a urea-induced protonation of the alpha
      aryldiazoester.

PMID- 24889758
TI  - The mTOR signaling pathway and neuronal stem/progenitor cell proliferation in the
      hippocampus are altered during the development of absence epilepsy in a genetic
      animal model.
AB  - Hyperactivation of mammalian target of rapamycin (mTOR) signaling pathway occurs
      after an epileptogenic insult and, its inhibition prevents the development of
      spontaneous seizures. We have recently demonstrated that mTOR's inhibition by
      rapamycin (started before seizure onset), permanently reduces the development of
      spontaneous absence seizures in WAG/Rij rats, an animal model of absence
      epilepsy; furthermore, mTOR phosphorylation was increased in adult WAG/Rij rats'
      cortex, but not other brain areas. However, it was not clear whether this
      hyperphosphorylation was a cause or a consequence of absence seizure. Here, we
      have addressed this issue by analyzing immunohistochemically: (1) the brain
      levels of total and phosphorylated mTOR in young (before seizures) and adult
      WAG/Rij rats; (2) the proliferation of hippocampal neuronal stem/progenitor cells
      assessed by BrdU analysis at different ages. WAG/Rij rats have higher levels of
      total mTOR in several brain areas than Wistar rats; phospho-mTOR staining is
      higher in young WAG/Rij rats than control and adult WAG/Rij rats. Finally, the
      age-related decline in hippocampal neural progenitor cell proliferation rate was
      slower in WAG/Rij than Wistar rats. Our results support a role for persistent
      mTOR activation and consequent change in hippocampal progenitor cell
      proliferation during the epileptogenic process leading to the development of
      absence seizures in WAG/Rij rats.

PMID- 24889760
TI  - Renal artery stenting in patients with uncontrolled hypertension: should we? And
      to whom?

PMID- 24889762
TI  - Evaluation of the known behavioral heterogeneity in conduct disorder to improve
      its assessment and treatment.
AB  - BACKGROUND: Conduct Disorder (CD) is among the most highly represented diagnostic
      problems in child and adolescent mental health treatment settings. There is a
      great deal of heterogeneity within the CD category, with potentially important
      implications for case conceptualization and treatment. The current review sought
      to detail forms of heterogeneity within CD, including callous-unemotional traits,
      comorbid Attention-Deficit Hyperactivity Disorder (ADHD), aggressive and
      nonaggressive antisocial behavior, and age of onset. METHODS: The current review
      summarizes research on etiological factors, correlates, and trajectories
      associated with distinguishable dimensions of CD, and considers how this
      heterogeneity should be incorporated into the assessment and treatment of CD.
      RESULTS: Callous-unemotional traits have been associated with a more severe and
      persistent form of CD, as have comorbid ADHD and child-onset CD. Aggressive
      antisocial behavior is a stable behavioral dimension that emerges in early
      childhood and is associated with high levels of neuroticism. Nonaggressive
      antisocial behavior demonstrates specific associations with impulsivity, is most
      frequent during adolescence, and evidences more moderate levels of stability.
      CONCLUSIONS: Conduct disorder is a highly heterogeneous disorder. Although the
      clinical implications of this heterogeneity are discussed, future research is
      clearly needed to shore up our understanding of the clinical ramifications of the
      sub-dimensions within CD.

PMID- 24889761
TI  - Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after
      influenza vaccination in rheumatoid arthritis patients.
AB  - Rituximab (RTX) treatment in rheumatoid arthritis (RA) patients severely hampers
      humoral response after influenza vaccination as determined by haemagglutination
      inhibition assay (HI). It is not known whether HI reflects both immunoglobulin
      (Ig)M and IgG (subclass) influenza response, and whether IgM antibodies
      contribute to the low rate of influenza infection seen in RA patients. Twenty RA
      patients on methotrexate (MTX), 23 on RTX and 28 healthy controls (HC) received
      trivalent influenza subunit vaccination. Before and 28 days after vaccination,
      H1N1- and H3N2-specific antibodies were measured by HI and by IgM and IgG
      (subclass) enzyme-linked immunosorbent assay (ELISA). B cell activating factor
      (BAFF) levels were determined in serum samples before vaccination. Vaccination
      induced a significant increase of IgM and IgG (IgG1 and IgG3) antibodies against
      both strains in the HC and MTX groups (all P < 0.01), but not in the RTX group.
      HI correlated significantly in all cases with IgG (IgG1) but not with IgM. In RTX
      late patients (RTX treatment 6-10 months before vaccination), IgG (IgG1 and IgG3)
      response to vaccination was restored, but not IgM response. BAFF levels were
      significantly increased in RA-RTX patients and correlated with total IgG levels.
      Haemagglutination inhibition assay, used as gold standard, detects primarily IgG
      (IgG1) responses. IgM- and IgG influenza-specific antibodies increase after
      vaccination in HC and RA patients except in patients on RTX treatment. BAFF
      levels are increased in both early and late RTX-treated patients, but do not
      correlate with an influenza-specific antibody response.

PMID- 24889763
TI  - Undifferentiated and differentiated adipose-derived stem cells improve nerve
      regeneration in a rat model of facial nerve defect.
AB  - Autologous nerve grafting is the current procedure used for repairing facial
      nerve gaps. As an alternative to this method, tissue engineering cell-based
      therapy using induced pluripotent stem cells, Schwann cells and bone marrow
      derived mesenchymal stem cells has been proposed. However, these cells have major
      problems, including tumorigenesis in induced pluripotent stem cells and
      invasiveness and limited tissue associated with harvesting for the other cells.
      Here, we investigated the therapeutic potential of adipose-derived stem cells
      (ASCs), which can be harvested easily and repeatedly by a minimally invasive
      liposuction procedure. The ASCs had characteristics of mesenchymal tissue
      lineages and could differentiate into Schwann-like cells that were relatively
      simple to isolate and expand in culture. In an in vivo study, a silicone conduit
      containing undifferentiated ASCs, differentiated ASCs or Schwann cells were
      transplanted, embedded in a collagen gel and the efficacy of repair of a 7 mm-gap
      in the rat facial nerve examined. Morphometric quantification analysis of
      regenerated facial nerves after a regeneration period of 13 weeks showed that
      undifferentiated ASCs, differentiated ASCs, and Schwann cells had similar
      potential for nerve regeneration. Furthermore, the functional recovery of facial
      nerve regeneration using a rat facial palsy scoring system in the three groups
      was close to that in autologous nerve graft positive controls. These findings
      suggest that undifferentiated and differentiated ASCs may both have therapeutic
      potential in facial nerve regeneration as a source of Schwann cells in cell-based
      therapy performed as an alternative to autologous nerve grafts. Copyright (c)
      2014 John Wiley & Sons, Ltd.

PMID- 24889764
TI  - Cytokine Expression at Different Stages of Influenza A(H1N1)pdm09 Virus Infection
      in the Porcine Lung, Using Laser Capture Microdissection.
AB  - Pandemic influenza A(H1N1)pdm09 virus has retained its ability to infect swine
      whilst developing the ability to transmit effectively between humans, thus making
      the pig a valuable model for studying disease pathogenesis in both species. Lung
      lesions in pigs caused by infection with influenza A viruses vary in both their
      severity and distribution with individual lung lobes exhibiting lesions at
      different stages of infection pathogenic development and disease resolution.
      Consequently, investigating interactions between the virus and host and their
      implications for disease pathogenesis can be complicated. Studies were undertaken
      to investigate the discrete expression of pro- and anti-inflammatory mediators
      during lung lesion formation in pigs during infection with influenza A(H1N1)pdm09
      (A/Hamburg/05/09) virus. Laser capture microdissection was used to identify and
      select lung lobules containing lesions at different stages of development.
      Dissected samples were analysed using quantitative RT-PCR to assess pro- and anti
      inflammatory cytokine mRNA transcripts. Differential expression of the immune
      mediators IL-8, IL-10 and IFN-gamma was observed depending upon the lesion stage
      assessed. Upregulation of IFN-gamma, IL-8 and IL-10 mRNA was observed in stage 2
      lesions, whereas decreased mRNA expression was observed in stage 3 lesions, with
      IL-8 actively downregulated when compared with controls in both stage 3 and stage
      4 lesions. This study highlighted the value of using laser capture
      microdissection to isolate specific tissue regions and investigate subtle
      differences in cytokine mRNA expression during lesion development in pigs
      infected with influenza A(H1N1)pdm09. 

PMID- 24889766
TI  - Breast cancer: post-mastectomy radiotherapy reduces recurrence and mortality.
AB  - The recent results of the Early Breast Cancer Trialists' Cooperative Group meta
      analysis have demonstrated that post-mastectomy radiotherapy reduces breast
      cancer recurrence and mortality in women with positive axillary lymph nodes
      independently from the number of the lymph nodes involved-with no significant
      effect in patients with node-negative axillary status.

PMID- 24889767
TI  - Gastric cancer drug trials - are women second class citizens?

PMID- 24889765
TI  - An exploration of the dynamic longitudinal relationship between mental health and
      alcohol consumption: a prospective cohort study.
AB  - BACKGROUND: Despite intense investigation, the temporal sequence between alcohol
      consumption and mental health remains unclear. This study explored the
      relationship between alcohol consumption and mental health over multiple
      occasions, and compared a series of competing theoretical models to determine
      which best reflected the association between the two. METHODS: Data from phases 5
      (1997 to 1999), 7 (2002 to 2004), and 9 (2007 to 2009) of the Whitehall II
      prospective cohort study were used, providing approximately 10 years of follow-up
      for 6,330 participants (73% men; mean +/- SD age 55.8 +/- 6.0 years). Mental
      health was assessed using the Short Form (SF)-36 mental health component score.
      Alcohol consumption was defined as the number of UK units of alcohol drunk per
      week. Four dynamic latent change score models were compared: 1) a baseline model
      in which alcohol consumption and mental health trajectories did not influence
      each other, 2) and model in which alcohol consumption influenced changes in
      mental health but mental health exerted no effect on changes in drinking and 3)
      vice versa, and (4) a reciprocal model in which both variables influenced changes
      in each other. RESULTS: The third model, in which mental health influenced
      changes in alcohol consumption but not vice versa, was the best fit. In this
      model, the effect of previous mental health on upcoming change in alcohol
      consumption was negative (gamma = -0.31, 95% CI -0.52 to -0.10), meaning that
      those with better mental health tended to make greater reductions (or shallower
      increases) in their drinking between occasions. CONCLUSIONS: Mental health
      appears to be the leading indicator of change in the dynamic longitudinal
      relationship between mental health and weekly alcohol consumption in this sample
      of middle-aged adults. In addition to fuelling increases in alcohol consumption
      among low-level consumers, poor mental health may also be a maintaining factor
      for heavy alcohol consumption. Future work should seek to examine whether there
      are critical levels of alcohol intake at which different dynamic relationships
      begin to emerge between alcohol-related measures and mental health.

PMID- 24889768
TI  - Gastric cancer drug trials - are women second class citizens?

PMID- 24889769
TI  - Chemotherapy: NEPA-a single oral dose providing effective prevention of
      chemotherapy-induced nausea and vomiting.

PMID- 24889771
TI  - The resident as teacher: Medical students' perception in a Spanish university.
AB  - BACKGROUND AND OBJECTIVES: Residents play an important but scanty assessed role
      in medical students teaching. The aim of this study was to assess the perception
      of medical students about residents' teaching activity. MATERIAL AND METHODS:
      Autofilled survey provided to medical students of the University of Alcala
      (Spain) in the final year in their school of medicine. Student opinion about care
      and teaching abilities of residents and physicians was evaluated using a 5-point
      Likert scale. RESULTS: 104 surveys were collected. A 69,9% of students consider
      that as much as 50% of their knowledge came from rounds with residents. Students
      believe that resident teaching lacks enough academical acknowledgment (94.2%);
      they estimate necessary to acquire teaching skills during residency (82,7%), and
      they would like to provide tutoring other medical students (88,5%). Students
      rated residents better than physicians on relational and motivational abilities.
      CONCLUSIONS: There is a positive view about resident as a teacher among medical
      students, which suggests the need to improve the resident's teaching skills.

PMID- 24889772
TI  - The Andres Laguna Master Lecture. Treatment of multiple myeloma.

PMID- 24889773
TI  - Urethral discharge and mucocutaneous involvement.

PMID- 24889770
TI  - Management of colorectal cancer presenting with synchronous liver metastases.
AB  - Up to a fifth of patients with colorectal cancer (CRC) present with synchronous
      hepatic metastases. In patients with CRC who present without intestinal
      obstruction or perforation and in whom comprehensive whole-body imaging confirms
      the absence of extrahepatic disease, evidence indicates a state of equipoise
      between several different management pathways, none of which has demonstrated
      superiority. Neoadjuvant systemic chemotherapy is advocated by current
      guidelines, but must be integrated with surgical management in order to remove
      the primary tumour and liver metastatic burden. Surgery for CRC with synchronous
      liver metastases can take a number of forms: the 'classic' approach, involving
      initial colorectal resection, interval chemotherapy and liver resection as the
      final step; simultaneous removal of the liver and bowel tumours with neoadjuvant
      or adjuvant chemotherapy; or a 'liver-first' approach (before or after systemic
      chemotherapy) with removal of the colorectal tumour as the final procedure. In
      patients with rectal primary tumours, the liver-first approach can potentially
      avoid rectal surgery in patients with a complete response to chemoradiotherapy.
      We overview the importance of precise nomenclature, the influence of clinical
      presentation on treatment options, and the need for accurate, up-to-date surgical
      terminology, staging tests and contemporary management options in CRC and
      synchronous hepatic metastatic disease, with an emphasis on multidisciplinary
      care. 

PMID- 24889774
TI  - Chagas disease reactivation in a patient non-Hodgkin's lymphoma.

PMID- 24889775
TI  - Left atrial spontaneous echo contrast and thrombus formation at septal puncture
      during percutaneous mitral valve repair with the MitraClip system of severe
      mitral regurgitation: a report of two cases.

PMID- 24889776
TI  - Carbon dioxide sensitivity of zeolitic imidazolate frameworks.
AB  - Zeolitic imidazolate frameworks of zinc, cobalt, and cadmium, including the
      framework ZIF-8 commercially sold as Basolite Z1200, exhibit surprising
      sensitivity to carbon dioxide under mild conditions. The frameworks chemically
      react with CO2 in the presence of moisture or liquid water to form carbonates.
      This effect, which has been previously not reported in metal-organic framework
      chemistry, provides an explanation for conflicting reports on ZIF-8 stability to
      water and is of outstanding significance for evaluating the potential
      applications of metal-organic frameworks, especially for CO2 sequestration. 

PMID- 24889777
TI  - Carbon-carbon cross-coupling reactions catalyzed by a two-coordinate nickel(II)
      bis(amido) complex via observable Ni(I) , Ni(II) , and Ni(III) intermediates.
AB  - Recently, the development of more sustainable catalytic systems based on abundant
      first-row metals, especially nickel, for cross-coupling reactions has attracted
      significant interest. One of the key intermediates invoked in these reactions is
      a Ni(III) -alkyl species, but no such species that is part of a competent
      catalytic cycle has yet been isolated. Herein, we report a carbon-carbon cross
      coupling system based on a two-coordinate Ni(II) -bis(amido) complex in which a
      Ni(III) -alkyl species can be isolated and fully characterized. This study
      details compelling experimental evidence of the role played by this Ni(III) 
      alkyl species as well as those of other key Ni(I) and Ni(II) intermediates. The
      catalytic cycle described herein is also one of the first examples of a two
      coordinate complex that competently catalyzes an organic transformation,
      potentially leading to a new class of catalysts based on the unique ability of
      first-row transition metals to accommodate two-coordinate complexes. 

PMID- 24889778
TI  - Adenosine receptor activation improves microcirculation in experimental
      intestinal ischemia/reperfusion.
AB  - Gut ischemia and reperfusion (IR), e.g. in small bowel transplantation or during
      resuscitation, may result in severe impairment of the intestinal
      microcirculation. Potential sequelae are mucosal damage, loss of intestinal
      barrier function, bacterial translocation, systemic inflammation, multiple organ
      failure and death. We hypothesized a protective role for extracellular adenosine
      signalling in intestinal IR injury. Using intravital microscopy we investigated
      the effects of the adenosine receptor (AR) agonist NECA (5'-N-ethyl carboxamide
      adenosine) on leukocyte-endothelial interactions and capillary perfusion in the
      intestinal microcirculation following intestinal IR. Six groups of Lewis rats (n
      = 44) were studied: control, NECA (5'-N-ethyl carboxamide adenosine), IR (30
      minutes of intestinal ischemia, 2 hours of reperfusion), IR + NECA, IR + NECA +
      MRS1754 (A(2B)AR antagonist), IR + NECA + DPCPX (A(1)AR antagonist). All
      substances were administered i.v. immediately after declamping of the superior
      mesenteric artery. Intravital microscopy was performed after 2 hours of
      reperfusion. Following IR we observed a significant increase of leukocyte
      adhesion in the intestinal submucosal venules and a reduced capillary perfusion
      within the muscular layers. NECA reduced leukocyte activation and improved
      capillary perfusion significantly. Administration of A(2B)AR antagonist
      completely reversed the NECA effect, whereas A(1)AR inhibition only partially
      abolished the action of NECA. The data support the hypothesis that adenosine
      signalling is involved in intestinal IR injury. A(2B)AR may be more important
      than A(1)AR because A(2B)AR inhibition by MRS1754 completely reversed the effect
      of the adenosine receptor agonist NECA.

PMID- 24889779
TI  - Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic
      sclerosis.
AB  - BACKGROUND: To date, there are no large studies on videocapsule endoscopy in
      systemic sclerosis (SSc). Consequently, the prevalence and features of
      gastrointestinal mucosal abnormalities in SSc have not been determined. AIMS: To
      determine both prevalence and characteristics of gastrointestinal mucosal
      abnormalities in unselected patients with SSc, using videocapsule endoscopy. To
      predict which SSc patients are at risk of developing potentially bleeding
      gastrointestinal vascular mucosal abnormalities. METHODS: Videocapsule endoscopy
      was performed on 50 patients with SSc. RESULTS: Prevalence of gastrointestinal
      mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were
      predominant, including: watermelon stomach (34.6%), gastric and/or small
      intestinal telangiectasia (26.9%) and gastric and/or small intestinal
      angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal
      lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P
      = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P =
      0.02), lower levels of ferritin (P < 0.0001) and anti-centromere antibody.
      CONCLUSIONS: Our study identifies a high frequency of gastrointestinal mucosal
      abnormalities in SSc, with a marked predominance of vascular mucosal damage.
      Furthermore, our study shows a strong correlation between gastrointestinal
      vascular mucosal lesions and presence of severe extra-digestive vasculopathy
      (digital ulcers and higher nailfold videocapillaroscopy scores). This latter
      supports the theory that SSc-related diffuse vasculopathy is responsible for both
      cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold
      videocapillaroscopy may be a helpful test for managing SSc patients. In fact,
      nailfold videocapillaroscopy score should be calculated routinely, as it may
      result in identification of SSc patients at higher risk of developing potentially
      bleeding gastrointestinal vascular mucosal lesions.

PMID- 24889780
TI  - HPV-avertable cancer risks in India: a pooled analysis of 9 observational
      studies.

PMID- 24889781
TI  - Self-assembly of fluorescent and magnetic Fe3O4@coordination polymer nanochains.
AB  - Fluorescent and magnetic Fe3O4@coordination polymer (Fe3O4@CP) nanochains are
      synthesized via a simple one-pot solvothermal reaction of magnetite (Fe3O4) and
      coordination polymer precursors in the presence of an external magnetic field.
      The shell thickness within Fe3O4@CPs was easily regulated by varying the amounts
      of coordination polymer precursors used during the reaction. 

PMID- 24889783
TI  - Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by
      osteoinductive calcium phosphate ceramics.
AB  - Porous calcium phosphate ceramics (CaP ceramics) could induce ectopic bone
      formation which was regulated by various signal molecules. In this work, bone
      marrow mesenchymal stem cells (MSCs) were cultured on the surface of
      osteoinductive hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramics
      in comparison with control (culture plate) for up to 14 days to detect the signal
      molecules which might be affected by the CaP ceramics. Without adding osteogenic
      factors, MSCs cultured on HA and BCP both expressed higher Runx2, Osterix,
      collagen type I, osteopontin, bone sialoprotein, and osteocalcin at various
      stages compared with control, thus confirmed the osteoblastic differentiation of
      MSCs. Later study demonstrated the messenger RNA level of bone morphogenetic
      protein 2 (BMP2) and BMP4 were also significantly enhanced by HA and BCP.
      Furthermore, Smad1, 4, 5, and Dlx5, the main molecules in the BMP/Smads signaling
      pathway, were upregulated by HA and BCP. Moreover, the higher expression of Smads
      and BMP2, 4 in BCP over HA, corresponded to the better performance of BCP in
      stimulating in vitro osteoblastic differentiation of MSCs. This was in accordance
      with the better osteoinductivity of BCP over HA in vivo. Altogether, these
      results implied that the CaP ceramics may initiate the osteoblastic
      differentiation of MSCs by influencing the expression of molecules in BMP/Smads
      pathway.

PMID- 24889784
TI  - Dramatic presentation of a giant fibrovascular polyp of Laimer's triangle.

PMID- 24889782
TI  - Diacylglycerol lipase regulates lifespan and oxidative stress response by
      inversely modulating TOR signaling in Drosophila and C. elegans.
AB  - Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling
      metabolism and lifespan. Although TOR signaling can be activated by a metabolite
      of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism
      through which DAG metabolism influences lifespan remains unknown. DAG is
      metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn
      glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and
      Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl
      1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and
      enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels
      are reduced following these manipulations, implying the involvement of TOR
      signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan,
      reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional
      results from genetic interaction studies are consistent with the hypothesis that
      DAG metabolism interacts with TOR and S6K signaling to affect longevity and
      oxidative stress resistance. These findings highlight conserved metabolic and
      genetic pathways that regulate aging. 

PMID- 24889785
TI  - The nutrition transition in the Venezuelan Amazonia: increased overweight and
      obesity with transculturation.
AB  - OBJECTIVES: Amerindians have a particularly high propensity to overweight and
      obesity as they change lifestyle and experience a nutrition transition. The aim
      of this study was to evaluate the effects of transculturation on nutritional
      status in three Amazonian Amerindian villages. METHODS: Nutritional status was
      assessed in 232 volunteers: 65 Yanomami from an isolated village and 167 Guahibo
      subjects from villages with intermediate and high levels of transculturation.
      RESULTS: There was a significant pattern of decreasing stunting and increasing
      overweight and obesity across the gradient of transculturation. From the jungle
      Yanomami to the intermediate and transculturated Guahibo, stunting was
      respectively 72, 55, and 39%, and children /adult overweight was 0, 3/44, and
      15/89%. These anthropometric-based patterns were confirmed by bioimpedance vector
      analysis. CONCLUSIONS: Transculturation in these Amerindian populations is
      associated with an increase in overweight and obesity coexisting with
      undernourished children.

PMID- 24889786
TI  - Beyond family satisfaction: Family-perceived involvement in residential care.
AB  - AIM: To explore perceived family involvement and its relationship with
      satisfaction and facility impressions. METHOD: A questionnaire was posted to
      residents' next of kin from four South Australian residential aged care
      facilities. RESULTS: One hundred and fifty next of kin participated in the
      survey. Family-perceived involvement was significantly and positively correlated
      with satisfaction and facility impressions. CONCLUSION: The findings of this
      study add to the limited body of research into family involvement in long-term
      residential care. Feedback from the family regarding particular aspects of
      involvement may also improve the experience of long-term care for both family and
      resident, and assist with the identification of specific issues towards which
      organisations may target their quality improvement efforts.

PMID- 24889787
TI  - Rejoinder: Combining biomarkers to optimize patient treatment recommendations.

PMID- 24889788
TI  - Risk factors associated with a thrombotic or bleeding event in patients treated
      with vitamin K antagonists.
AB  - AIM: To identify, in a case-control study, the risk factors associated with a
      thrombotic or bleeding event in patients treated with vitamin K antagonists.
      MATERIALS AND METHODS: We performed a single-centre observational study during a
      three-month period where we consecutively included patients admitted to the
      emergency department of a secondary-level hospital and treated with vitamin K
      antagonists, regardless the reason for admission. Patients admitted for a
      thrombotic or bleeding event were included as cases and the other patients served
      as controls. Main thrombotic or bleeding risk factors during vitamin K antagonist
      therapy were a priori identified in literature and tested in conditional logistic
      regression. RESULTS: Two hundred and forty subjects were identified, 40 of which
      (17%) were admitted for a bleeding event, 19 (8%) for a thrombotic event and 181
      (75%) for another reason. Over 85% of patients were treated with fluindione. No
      risk factor was significantly associated with bleeding or thrombotic event in
      patients treated with vitamin K antagonist. Patients presenting a thrombotic
      event were however more likely to have a chronic respiratory disease.
      CONCLUSIONS: In this study, no risk factor significantly associated with a
      bleeding or thrombotic event in patients treated with vitamin K antagonist were
      identified. The occurrence of these events supposes other risk factors, including
      potential genetic polymorphisms that should be considered in future studies.

PMID- 24889789
TI  - Congenital intestinal duplication in an adult.
AB  - Congenital intestinal duplication is an anomaly most commonly diagnosed in
      children under the age of 2. Rarely, it is seen in adults who remain asymptomatic
      or present with vague abdominal symptoms. Here, we describe the case of a 33-year
      old female who was diagnosed intraoperatively with congenital intestinal
      duplication after suffering from a year of vague abdominal complaints. 

PMID- 24889790
TI  - Giant adrenal myelolipoma.

PMID- 24889791
TI  - Video-Assisted Thoracoscopic Extirpation of the Tracheobronchial Lymph Nodes in
      Dogs.
AB  - OBJECTIVE: To describe a technique for video-assisted thoracoscopic surgery
      (VATS) extirpation of the tracheobronchial lymph nodes (TBLN), and to describe
      the quality of biopsy specimens obtained. DESIGN: Experimental study. ANIMALS:
      Purpose-bred male hound-mix research dogs (n = 8). METHODS: Dogs were randomized
      to groups of left-sided or right-sided VATS approaches. One lung ventilation was
      used and TBLN dissection was achieved using a vessel-sealing device. RESULTS:
      TBLNs ipsilateral to the approach were successfully identified and removed
      thoracoscopically in 7 dogs. A 3-port technique was used in 6 dogs and 4 ports
      were used in 2 dogs. Observed complications included mild-moderate hemorrhage
      from the perinodal tissue controlled thoracoscopically (n = 2), inability to
      locate any TBLN (1), and difficulty achieving or maintaining one-lung ventilation
      (4). No other major complications occurred and all dogs recovered uneventfully.
      Median percentage surface area of the bisected lymph nodes affected by crush
      artifact was 20% (range, 0-40%). Areas of crush artifact were present in central
      (7/11) and peripheral (9/11) locations. CONCLUSIONS AND CLINICAL RELEVANCE:
      Thoracoscopic TBLN extirpation is a feasible technique in dogs with normal TBLN
      and may be useful for obtaining more detailed staging on microscopic disease
      status in oncologic patients with normal-sized TBLNs. Further study is warranted
      to determine the feasibility and limitations of this technique in clinical
      patients with overt lymphadenopathy.

PMID- 24889792
TI  - Leaching assessment of concrete made of recycled coarse aggregate: physical and
      environmental characterisation of aggregates and hardened concrete.
AB  - Each year, millions of tonnes of waste are generated worldwide, partially through
      the construction and demolition of buildings. Recycling the resulting waste could
      reduce the amount of materials that need to be manufactured. Accordingly, the
      present work has analysed the potential reuse of construction waste in concrete
      manufacturing by replacing the natural aggregate with recycled concrete coarse
      aggregate. However, incorporating alternative materials in concrete manufacturing
      may increase the pollutant potential of the product, presenting an environmental
      risk via ground water contamination. The present work has tested two types of
      concrete batches that were manufactured with different replacement percentages.
      The experimental procedure analyses not only the effect of the portion of
      recycled aggregate on the physical properties of concrete but also on the
      leaching behaviour as indicative of the contamination degree. Thus, parameters
      such as slump, density, porosity and absorption of hardened concrete, were
      studied. Leaching behaviour was evaluated based on the availability test
      performed to three aggregates (raw materials of the concrete batches) and on the
      diffusion test performed to all concrete. From an environmental point of view,
      the question of whether the cumulative amount of heavy metals that are released
      by diffusion reaches the availability threshold was answered. The analysis of
      concentration levels allowed the establishment of different groups of metals
      according to the observed behaviour, the analysis of the role of pH and the
      identification of the main release mechanisms. Finally, through a statistical
      analysis, physical parameters and diffusion data were interrelated. It allowed
      estimating the relevance of porosity, density and absorption of hardened concrete
      on diffusion release of the metals in study. 

PMID- 24889793
TI  - Quantification of the resource recovery potential of municipal solid waste
      incineration bottom ashes.
AB  - Municipal solid waste incineration (MSWI) plays an important role in many
      European waste management systems. However, increasing focus on resource
      criticality has raised concern regarding the possible loss of critical resources
      through MSWI. The primary form of solid output from waste incinerators is bottom
      ashes (BAs), which also have important resource potential. Based on a full-scale
      Danish recovery facility, detailed material and substance flow analyses (MFA and
      SFA) were carried out, in order to characterise the resource recovery potential
      of Danish BA: (i) based on historical and experimental data, all individual flows
      (representing different grain size fractions) within the recovery facility were
      quantified, (ii) the resource potential of ferrous (Fe) and non-ferrous (NFe)
      metals as well as rare earth elements (REE) was determined, (iii) recovery
      efficiencies were quantified for scrap metal and (iv) resource potential
      variability and recovery efficiencies were quantified based on a range of ashes
      from different incinerators. Recovery efficiencies for Fe and NFe reached 85% and
      61%, respectively, with the resource potential of metals in BA before recovery
      being 7.2%ww for Fe and 2.2%ww for NFe. Considerable non-recovered resource
      potential was found in fine fraction (below 2mm), where approximately 12% of the
      total NFe potential in the BA were left. REEs were detected in the ashes, but the
      levels were two or three orders of magnitude lower than typical ore
      concentrations. The lack of REE enrichment in BAs indicated that the post
      incineration recovery of these resources may not be a likely option with current
      technology. Based on these results, it is recommended to focus on limiting REE
      containing products in waste for incineration and improving pre-incineration
      sorting initiatives for these elements. 

PMID- 24889795
TI  - T regulatory lymphocytes in patients with endometriosis.
AB  - The present study aimed to investigate the presence of T regulatory cells (Tregs)
      in the peripheral blood (PB) and peritoneal fluid (PF) in females with
      endometriosis. The present study included 42 patients who underwent laparoscopy
      between 2010 and 2011. Flow cytometry was used to determine the percentage of
      Tregs in the PF and PB of the patients. No significant difference was observed in
      the percentage of Tregs in the patients in the endometriosis group compared with
      those in the control group in the PF (9.1+/-5.4 vs. 9.1+/-3.8%) or the PB (6.5+/
      3.2 vs. 6.5+/-3.7%). However, the percentage of Tregs was found to be higher in
      the PF compared with the PB in the patients in the endometriosis and control
      groups, but significance was found only in those in the control group.
      Furthermore, no significant difference was observed in the Treg concentration in
      the patients with early stage (I/II) endometriosis compared with those with late
      stage (III/IV) endometriosis. Moreover, no significant correlation was found
      between the percentage of Tregs and the white blood cell count, lymphocyte count
      or CA125 concentration in the patients. These findings suggest that the local
      host-defense mechanism is deficient in patients with endometriosis, thus
      endometriosis should not be treated as an autoimmune condition. 

PMID- 24889794
TI  - Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional
      and squamous cell carcinoma of the bladder: effect on survival and bladder
      preservation.
AB  - BACKGROUND: Despite aggressive local therapy, patients with locally advanced
      bladder cancer have a significant risk of distant metastases. This study
      evaluated the role of neoadjuvant combination chemotherapy with
      gemcitabine/cisplatin (GC) in improving the outcome of this group of patients
      over radical cystectomy alone. PATIENTS AND METHODS: A total of 114 patients with
      newly diagnosed bladder cancer (T3-4, N0-2, M0) were randomized to radical
      cystectomy alone or initial 3 cycles of GC, then managed according to response.
      Patients who achieved complete response completed 6 cycles of GC followed by
      local radiation therapy (RT) only. If tumors were downstaged to T1, complete
      transurethral resection was done, followed by 3 cycles of GC and then RT.
      Patients with partial response underwent radical cystectomy followed by 3 cycles
      of GC. Patients with stable disease or disease progression underwent radical
      cystectomy. RESULTS: The overall response rate to GC was 55.1%, and complete
      response was achieved in 28.6%. The 3-year overall survival (OS) was 51.9% versus
      51.2% in the chemotherapy and surgery arms, respectively (P = .399). The 3-year
      disease-free survival was 31.8% in the chemotherapy arm and 45.1% in the surgery
      arm (P = .06). Bladder preservation was achieved in 22.5% of patients in the
      neoadjuvant arm. OS was 78% in responding patients and 100% in patients with
      complete response. CONCLUSION: Neoadjuvant GC did not improve survival in locally
      advanced bladder cancer over radical cystectomy alone. However, bladder
      preservation was feasible, and OS in responding patients was impressive.
      Therefore, predictive models to select patients are needed. This is the largest
      prospective study of squamous cell carcinoma and transitional cell carcinoma
      using neoadjuvant GC.

PMID- 24889796
TI  - A microgroove patterned multiwell cell culture plate for high-throughput studies
      of cell alignment.
AB  - Grooved substrates are commonly used to guide cell alignment and produce in vitro
      tissues that mimic certain aspects of in vivo cellular organization. These more
      sophisticated tissues provide valuable in vitro models for testing drugs and for
      dissecting out molecular mechanisms that direct tissue organization. To increase
      the accessibility of these tissue models we describe a simple and yet
      reproducible strategy to produce 1 um-spaced grooved well plates suitable for
      conducting automated analysis of cellular responses. We characterize the
      alignment of four human cell types: retinal epithelial cells, umbilical vein
      endothelial cells, foreskin fibroblasts, and human pluripotent stem-cell-derived
      cardiac cells on grooves. We find all cells align along the grooves to differing
      extents at both sparse and confluent densities. To increase the sophistication of
      in vitro tissue organization possible, we also created hybrid substrates with
      controlled patterns of microgrooved and flat regions that can be identified in
      real-time using optical microscopy. Using our hybrid patterned surfaces we
      explore: (i) the ability of neighboring cells to provide a template to organize
      surrounding cells that are not directly exposed to grooved topographic cues, and
      (ii) the distance over which this template effect can operate in confluent cell
      sheets. We find that in fibroblast sheets, but not epithelial sheets, cells
      aligned on grooves can direct alignment of neighboring cells in flat regions over
      a limited distance of approximately 200 MUm. Our hybrid surface plate provides a
      novel tool for studying the collective response of groups of cells exposed to
      differential topographical cues.

PMID- 24889797
TI  - In vitro biocompatibility and cellular interactions of a chitosan/dextran-based
      hydrogel for postsurgical adhesion prevention.
AB  - In this paper, we report the in vitro biocompatibility and cellular interactions
      of a chitosan/dextran-based (CD) hydrogel and its components as determined by
      mutagenicity, cytotoxicity, cytokine/chemokine response, and wound healing
      assays. The CD hydrogel, developed for postsurgical adhesion prevention in ear,
      nose, and throat surgeries, was shown by previously published experiments in
      animal and human trials to be effective. The hydrogel was synthesized from the
      reaction between succinyl chitosan (SC) and oxidized dextran (DA). Cytotoxicity
      was assessed in an xCELLigence system and cytokine/chemokine responses were
      measured by ELISA in human macrophage, nasopharyngeal epithelial, and dermal
      fibroblast cells. A wound healing model utilized nasopharyngeal epithelial cells.
      CD hydrogel and DA were nonmutagenic in the Ames test. CD hydrogel showed
      moderate cytotoxicity for the cell lines, DA being the cytotoxic component. Some
      inhibition of wound healing occurred due to the cytotoxic nature of DA. Cells
      cultured with CD hydrogel showed no increase in TNF-alpha, IL-10, and IL-8
      levels. It is hypothesized that the cytotoxicity of DA is moderated when reacted
      with SC and that CD hydrogel inhibits unwanted fibroblastic invasion preventing
      scarring and adhesions. Together with the previously published human and animal
      trial data, the results indicate CD hydrogel is biocompatible in the setting of
      endoscopic sinus surgery. This work represents the first study of CD hydrogel
      with human cell lines and provides essential information for its future
      application in biomedicine.

PMID- 24889798
TI  - Biomarkers of oxidative stress and inflammation after wood smoke exposure in a
      reconstructed Viking Age house.
AB  - Exposure to particles from combustion of wood is associated with respiratory
      symptoms, whereas there is limited knowledge about systemic effects. We
      investigated effects on systemic inflammation, oxidative stress and DNA damage in
      humans who lived in a reconstructed Viking Age house, with indoor combustion of
      wood for heating and cooking. The subjects were exposed to high indoor
      concentrations of PM2.5 (700-3,600 ug/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154
      ug/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of
      genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA
      glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood
      mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1,
      CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of
      C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol,
      triglycerides, and high-density lipoproteins. The wood smoke exposure was
      associated with decreased serum levels of sICAM-1, and a tendency to decreased
      sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes
      expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d,
      and CD62L on monocytes after the stay in the house. In conclusion, even a high
      inhalation exposure to wood smoke was associated with limited systemic effects on
      markers of oxidative stress, DNA damage, inflammation, and monocyte activation.

PMID- 24889799
TI  - Growth hormone/insulin-like growth factor 1 dynamics in adult living donor liver
      transplantation.
AB  - End-stage liver disease is accompanied by decreased serum levels of insulin-like
      growth factor 1 (IGF1) and inversely increased serum levels of growth hormone
      (GH). Previous reports have demonstrated rapid GH/IGF1 axis recovery after
      orthotopic liver transplantation. This study investigated the effect in an adult
      to-adult living donor liver transplantation (LDLT) model and characterized
      GH/IGF1 alterations and liver regeneration in both donors and recipients.
      Sequential blood samples were prospectively collected from 30 donor-recipient
      pairs during the perioperative course of LDLT. A distinct set of biochemical
      parameters, including serum GH, serum IGF1, and standard liver blood tests, was
      analyzed at different time points (preoperatively and during 12 months of follow
      up after surgery). Recipients showed significantly higher GH serum levels and
      lower IGF1 serum levels in comparison with donors before surgery and throughout
      the first postoperative days (PODs). The GH serum levels of recipients declined,
      whereas donor levels inversely increased during the early postoperative period to
      a normal range. Recipients' IGF1 serum levels were restored within the first
      operative week. In parallel, donor IGF1 levels decreased by 50% after living
      donation, and preoperative serum levels were restored after 6 months. Donors
      showed delayed recovery of liver function in comparison with recipients. The
      dynamics of IGF1 strongly correlated with routine laboratory parameters of liver
      function. In conclusion, recipients showed a rapid recovery of the GH/IGF1
      hormonal axis and liver function after LDLT, whereas donors showed altered GH
      signaling and regenerative delay in the early PODs after living donation.

PMID- 24889800
TI  - All-atom empirical potential for molecular modeling and dynamics studies of
      proteins.
AB  - New protein parameters are reported for the all-atom empirical energy function in
      the CHARMM program. The parameter evaluation was based on a self-consistent
      approach designed to achieve a balance between the internal (bonding) and
      interaction (nonbonding) terms of the force field and among the solvent-solvent,
      solvent-solute, and solute-solute interactions. Optimization of the internal
      parameters used experimental gas-phase geometries, vibrational spectra, and
      torsional energy surfaces supplemented with ab initio results. The peptide
      backbone bonding parameters were optimized with respect to data for N
      methylacetamide and the alanine dipeptide. The interaction parameters,
      particularly the atomic charges, were determined by fitting ab initio interaction
      energies and geometries of complexes between water and model compounds that
      represented the backbone and the various side chains. In addition, dipole
      moments, experimental heats and free energies of vaporization, solvation and
      sublimation, molecular volumes, and crystal pressures and structures were used in
      the optimization. The resulting protein parameters were tested by applying them
      to noncyclic tripeptide crystals, cyclic peptide crystals, and the proteins
      crambin, bovine pancreatic trypsin inhibitor, and carbonmonoxy myoglobin in vacuo
      and in crystals. A detailed analysis of the relationship between the alanine
      dipeptide potential energy surface and calculated protein phi, chi angles was
      made and used in optimizing the peptide group torsional parameters. The results
      demonstrate that use of ab initio structural and energetic data by themselves are
      not sufficient to obtain an adequate backbone representation for peptides and
      proteins in solution and in crystals. Extensive comparisons between molecular
      dynamics simulations and experimental data for polypeptides and proteins were
      performed for both structural and dynamic properties. Energy minimization and
      dynamics simulations for crystals demonstrate that the latter are needed to
      obtain meaningful comparisons with experimental crystal structures. The presented
      parameters, in combination with the previously published CHARMM all-atom
      parameters for nucleic acids and lipids, provide a consistent set for condensed
      phase simulations of a wide variety of molecules of biological interest. 

PMID- 24889801
TI  - Biosimilar recombinant follicle stimulating hormones in infertility treatment.
AB  - INTRODUCTION: Follicle stimulating hormone (FSH) is a glycoprotein hormone
      essential for reproduction both in females and males and it is physiologically
      produced by the anterior pituitary gland in several isoforms. This heterogeneity
      is typical also of FSH-containing compounds, both urinary-derived and recombinant
      products. These compounds are widely used in assisted reproductive technologies
      (ART), to induce multifollicular development. Recently, the increased cost
      pressure on healthcare systems and the patent expiration date of widely used
      biotechnology-derived, recombinant FSH, prompted the pharmaceutical interest in
      FSH biosimilars. AREAS COVERED: In 2014, two FSH biosimilars obtained marketing
      authorization by the European Medicines Agency. Here, we review the biology of
      natural, extractive and recombinant FSH, the current state of biosimilar FSH,
      including the legal framework, and aspects to be considered in biosimilar FSH
      usage. Literature search methodologies included Medline and PubMed research.
      EXPERT OPINION: Biosimilar FSH preparations are expected to be biologically and
      clinically 'non inferior' to the originator product. However, the impact of FSH
      biosimilars on cost and outcomes of ART is far from being established, since
      insufficient information is available to demonstrate the pros and cons in the
      long-term application.

PMID- 24889803
TI  - Transfusion in military and civilian trauma and major haemorrhage.

PMID- 24889802
TI  - Effect of non-stationary climate on infectious gastroenteritis transmission in
      Japan.
AB  - Local weather factors are widely considered to influence the transmission of
      infectious gastroenteritis. Few studies, however, have examined the non
      stationary relationships between global climatic factors and transmission of
      infectious gastroenteritis. We analyzed monthly data for cases of infectious
      gastroenteritis in Fukuoka, Japan from 2000 to 2012 using cross-wavelet coherency
      analysis to assess the pattern of associations between indices for the Indian
      Ocean Dipole (IOD) and El Nino Southern Oscillation (ENSO). Infectious
      gastroenteritis cases were non-stationary and significantly associated with the
      IOD and ENSO (Multivariate ENSO Index [MEI], Nino 1 + 2, Nino 3, Nino 4, and Nino
      3.4) for a period of approximately 1 to 2 years. This association was non
      stationary and appeared to have a major influence on the synchrony of infectious
      gastroenteritis transmission. Our results suggest that non-stationary patterns of
      association between global climate factors and incidence of infectious
      gastroenteritis should be considered when developing early warning systems for
      epidemics of infectious gastroenteritis. 

PMID- 24889804
TI  - The school of hard knocks: what we've learned and relearned about transfusion in
      a decade of global conflict.

PMID- 24889805
TI  - State of the art: massive transfusion.
AB  - The aim of this article was to review recent developments in the resuscitation of
      both trauma and non-trauma patients in haemorrhagic shock. Strategies for the
      resuscitation of massively haemorrhaging patients and the use of massive
      transfusion protocols (MTPs) have been a major focus of the trauma literature
      over the past several years. The application of haemostatic resuscitation
      practices and MTPs to non-trauma populations has long been in practice, but has
      only recently been the subject of active research. Medline and PubMed were
      reviewed for 'massive transfusion' (MT) from 2012 to present. Non-English and
      paediatric articles were excluded. Articles were systematically reviewed for
      their relevance to MT. There were eight major areas of development identified. In
      recent MT literature, there was an increased focus on massively haemorrhaging non
      trauma patients, the role of acute traumatic coagulopathy, the use of
      thromboelastography (TEG), and the impact of MTPs on blood product waste and
      efficiency of product delivery. Other developments included additional MT
      prediction tools and The PRospective Observational Multicenter Major Trauma
      Transfusion (PROMMTT) study. There was also interest in re-evaluating the
      clinical relevance of the current MT definition and identifying new foci for MT.
      These recent developments reflect efforts to better understand and manage non
      traumatic haemorrhage and to address prior limitations in the trauma literature.
      Inevitably, new questions have been raised, which will likely direct ongoing and
      future research in MT.

PMID- 24889806
TI  - Obituary: John Jenkins, 1921-2014.

PMID- 24889808
TI  - Perceived marginalization and aggression: a longitudinal study with low-educated
      adolescents.
AB  - Social exclusion can evoke aggression. In the past two decades research has
      demonstrated this effect both for interpersonal and societal forms of exclusion.
      In addition, recent violent uprisings, like the London riots in August 2011, have
      been linked to social exclusion in the media. However, so far there is a lack of
      longitudinal studies which examine the aggression-enhancing effect of societal
      level exclusion (i.e., marginalization) in disadvantaged groups. This research
      investigates the impact of perceived marginalization on aggression in a sample of
      N = 181 adolescents with a low educational background by means of a two-wave
      longitudinal study. The results of structural equation analyses are consistent
      with the hypothesis that perceived marginalization enhances aggression, and that
      this effect is mediated by the extent of negative societal meta-stereotypes.
      Furthermore, the reverse path from aggression to perceptions of marginalization
      is also significant. We discuss the implications of these findings and highlight
      practical consequences. 

PMID- 24889809
TI  - Chemical fingerprint and simultaneous determination of alkaloids and flavonoids
      in aerial parts of genus Peganum indigenous to China based on HPLC-UV:
      application of analysis on secondary metabolites accumulation.
AB  - The aerial parts of genus Peganum are officially used in traditional Chinese
      medicine. The paper aims to establish a high-performance liquid chromatography
      (HPLC) method for fingerprint analysis and simultaneous determination of three
      alkaloids and two flavonoids in aerial parts of genus Peganum, and to analyze
      accumulative difference of secondary metabolites in inter-species, individuals of
      plants, inter-/intra-population and from different growing seasons. HPLC analysis
      was performed on a C18 column with gradient elution using 0.1% trifloroacetic
      acid and acetonitrile as mobile phase and detected at 265 nm, by conventional
      methodology validation. For fingerprint analysis, the RSDs of relative retention
      time and relative peak area of the characteristic peaks were within 0.07-0.78 and
      0.94-9.09%, respectively. For simultaneous determination of vasicine, harmaline,
      harmine, deacetylpeganetin and peganetin, all calibration curves showed good
      linearity (r > 0.9990) within the test range. The relative standard deviations of
      precision, repeatability and stability test did not exceed 2.37, 2.68 and 2.67%,
      respectively. The average recoveries for the five analytes were between 96.47 and
      101.20%. HPLC fingerprints play a minor role in authenticating and
      differentiating the herbs of different species of genus Peganum. However, the
      secondary metabolites levels of alkaloids and flavonoids in aerial parts of genus
      Peganum rely on species-, habitat-, and growth season-dependent accumulation.

PMID- 24889810
TI  - O-acyl isopeptide method: development of an O-acyl isodipeptide unit for Boc SPPS
      and its application to the synthesis of Abeta1-42 isopeptide.
AB  - The O-acyl isopeptide method was developed for the efficient preparation of
      difficult sequence-containing peptide. Furthermore, development of the O-acyl
      isodipeptide unit for Fmoc chemistry simplified its synthetic procedure by solid
      phase peptide synthesis. Here, we report a novel isodipeptide unit for Boc
      chemistry, and the unit was successfully applied to the synthesis of amyloid beta
      peptide. Combination of Boc chemistry and the isodipeptide unit would be an
      effective method for the synthesis of many difficult peptides. Copyright (c) 2014
      European Peptide Society and John Wiley & Sons, Ltd. 

PMID- 24889812
TI  - Cardiac screening in infants with infantile hemangiomas before propranolol
      treatment.
AB  - There is no uniform pretreatment cardiac evaluation for infants treated with oral
      propranolol, which is now the drug of choice for hemangiomas of infancy requiring
      systemic medical intervention. The aim of this study was to report and evaluate
      the findings of pretreatment cardiac evaluation. Data were reviewed for patients
      evaluated by a single hemangioma specialist and a single pediatric cardiologist
      prior to initiation of propranolol for infantile hemangioma. Cardiac evaluation
      included a complete echocardiogram. From July 2009 through January 2013, 239
      consecutive patients 12 months of age or younger (median 2.7 months) were
      screened. No patients had cardiac contraindications to propranolol. However, 50
      patients (21%) had an abnormal echocardiogram: 39 atrial septal defects (5
      associated with right heart enlargement), 6 ventricular septal defects, 2 patent
      ductus arteriosus, 1 aortic coarctation, 1 pulmonary valve stenosis, and 1
      aberrant subclavian artery. Overall, 69 patients had an audible heart murmur, 44
      of which were not associated with pathologic findings on echocardiogram. All
      patients with a ventricular septal defect and 16 of 39 with an atrial septal
      defect had a murmur. Two of seven patients with PHACE syndrome had cardiac
      anomalies. None of the findings precluded the use of propranolol. Assisted
      reproductive technologies were used in 18% of pregnancies, including in vitro
      fertilization in 12%. Cardiac contraindications to propranolol treatment are
      uncommon in patients with infantile hemangioma. However, anatomic abnormalities
      were more common than reported in the general population. Further study is
      necessary to determine whether there is a pathogenic relationship between cardiac
      defects and nonsyndromic infantile hemangioma. 

PMID- 24889813
TI  - Molecular evidence for ancient relicts of arctic-alpine plants in East Asia.
AB  - Following climate cooling at the end of the Tertiary, arctic-alpine plants
      attained most of their extant species diversity. Because East Asia was not
      heavily glaciated, the importance of this region as a location for the long-term
      persistence of these species and their subsequent endemism during the Pleistocene
      was proposed in early discussions of phytogeography. However, this hypothesis
      remains to be fully tested. Here, we address this hypothesis by elucidating the
      phylogenetic history of Phyllodoce (Ericaceae). A phylogenetic tree based on
      multiple nuclear loci revealed that Phyllodoce nipponica was not derived from
      widespread species such as the arctic-alpine Phyllodoce caerulea, but rather
      represented an independent lineage sister to the clade of widespread relatives.
      Molecular dating indicated a mid-Pleistocene divergence of P. nipponica. These
      findings exclude the hypothesis that P. nipponica was derived from an arctic
      alpine species that extended its range southwards during recent glacial periods.
      Instead, our results support the hypothesis that P. nipponica is an ancestral
      species which persisted in the Japanese archipelago during the mid- and late
      Pleistocene. Our findings demonstrate support for the early proposal and shed
      light on the importance of the Japanese archipelago for the evolution and
      persistence of arctic-alpine species. 

PMID- 24889811
TI  - The F pilus mediates a novel pathway of CDI toxin import.
AB  - Contact-dependent growth inhibition (CDI) is a widespread form of inter-bacterial
      competition that requires direct cell-to-cell contact. CDI(+) inhibitor cells
      express CdiA effector proteins on their surface. CdiA binds to specific receptors
      on susceptible target bacteria and delivers a toxin derived from its C-terminal
      region (CdiA-CT). Here, we show that purified CdiA-CT(536) toxin from
      uropathogenic Escherichia coli 536 translocates into bacteria, thereby by-passing
      the requirement for cell-to-cell contact during toxin delivery. Genetic analyses
      demonstrate that the N-terminal domain of CdiA-CT(536) is necessary and
      sufficient for toxin import. The CdiA receptor plays no role in this import
      pathway; nor do the Tol and Ton systems, which are exploited to internalize
      colicin toxins. Instead, CdiA-CT(536) import requires conjugative F pili. We
      provide evidence that the N-terminal domain of CdiA-CT(536) interacts with F
      pilin, and that pilus retraction is critical for toxin import. This pathway is
      reminiscent of the strategy used by small RNA leviviruses to infect F(+) cells.
      We propose that CdiA-CT(536) mimics the pilin-binding maturation proteins of
      leviviruses, allowing the toxin to bind F pili and become internalized during
      pilus retraction. 

PMID- 24889814
TI  - The novel pterostilbene derivative ANK-199 induces autophagic cell death through
      regulating PI3 kinase class III/beclin 1/Atg-related proteins in cisplatin
      resistant CAR human oral cancer cells.
AB  - Pterostilbene is an effective chemopreventive agent against multiple types of
      cancer cells. A novel pterostilbene derivative, ANK-199, was designed and
      synthesized by our group. Its antitumor activity and mechanism in cisplatin
      resistant CAR human oral cancer cells were investigated in this study. Our
      results show that ANK-199 has an extremely low toxicity in normal oral cell
      lines. The formation of autophagic vacuoles and acidic vesicular organelles
      (AVOs) was observed in the ANK-199-treated CAR cells by monodansylcadaverine
      (MDC) and acridine orange (AO) staining, suggesting that ANK-199 is able to
      induce autophagic cell death in CAR cells. Neither DNA fragmentation nor DNA
      condensation was observed, which means that ANK-199-induced cell death is not
      triggered by apoptosis. In accordance with morphological observation, 3-MA, a
      specific inhibitor of PI3K kinase class III, can inhibit the autophagic vesicle
      formation induced by ANK-199. In addition, ANK-199 is also able to enhance the
      protein levels of autophagic proteins, Atg complex, beclin 1, PI3K class III and
      LC3-II, and mRNA expression of autophagic genes Atg7, Atg12, beclin 1 and LC3-II
      in the ANK-199-treated CAR cells. A molecular signaling pathway induced by ANK
      199 was therefore summarized. Results presented in this study show that ANK-199
      may become a novel therapeutic reagent for the treatment of oral cancer in the
      near future (patent pending).

PMID- 24889815
TI  - Measurement of naphthenic acids in the receiving waters around an offshore oil
      platform by passive sampling.
AB  - Polar organic chemical integrative samplers (POCIS) were deployed in the vicinity
      of an offshore oil installation and analyzed for naphthenic acids (NAs). The
      POCIS accumulated a range of mono- to tetracyclic NAs, with different degrees of
      alkylation, with monocyclic acids being the most abundant. Currently, POCIS or
      similar polar samplers may be the only way to measure exposure to NAs from
      offshore discharges in situ. In addition, they may be a valuable tool for
      monitoring similar organic acids in general.

PMID- 24889816
TI  - Hygiene and health: systematic review of handwashing practices worldwide and
      update of health effects.
AB  - OBJECTIVE: To estimate the global prevalence of handwashing with soap and derive
      a pooled estimate of the effect of hygiene on diarrhoeal diseases, based on a
      systematic search of the literature. METHODS: Studies with data on observed rates
      of handwashing with soap published between 1990 and August 2013 were identified
      from a systematic search of PubMed, Embase and ISI Web of Knowledge. A separate
      search was conducted for studies on the effect of hygiene on diarrhoeal disease
      that included randomised controlled trials, quasi-randomised trials with control
      group, observational studies using matching techniques and observational studies
      with a control group where the intervention was well defined. The search used
      Cochrane Library, Global Health, BIOSIS, PubMed, and Embase databases
      supplemented with reference lists from previously published systematic reviews to
      identify studies published between 1970 and August 2013. Results were combined
      using multilevel modelling for handwashing prevalence and meta-regression for
      risk estimates. RESULTS: From the 42 studies reporting handwashing prevalence we
      estimate that approximately 19% of the world population washes hands with soap
      after contact with excreta (i.e. use of a sanitation facility or contact with
      children's excreta). Meta-regression of risk estimates suggests that handwashing
      reduces the risk of diarrhoeal disease by 40% (risk ratio 0.60, 95% CI 0.53
      0.68); however, when we included an adjustment for unblinded studies, the effect
      estimate was reduced to 23% (risk ratio 0.77, 95% CI 0.32-1.86). CONCLUSIONS: Our
      results show that handwashing after contact with excreta is poorly practiced
      globally, despite the likely positive health benefits.

PMID- 24889818
TI  - Genomic and morphological analysis of a semipermeable avian hybrid zone suggests
      asymmetrical introgression of a sexual signal.
AB  - Hybrid zones are geographic regions where differentiated taxa meet and
      potentially exchange genes. Increasingly, genomic analyses have demonstrated that
      many hybrid zones are semipermeable boundaries across which introgression is
      highly variable. In some cases, certain alleles penetrate across the hybrid zone
      in only one direction, recombining into the alternate genome. We investigated
      this phenomenon using genomic (genotyping-by-sequencing) and morphological
      (plumage reflectance spectrophotometry) analyses of the hybrid zone between two
      subspecies of the red-backed fairy-wren (Malurus melanocephalus) that differ
      conspicuously in a sexual signal, male back plumage color. Geographic cline
      analyses revealed a highly variable pattern of differential introgression, with
      many narrow coincident clines combined with several significantly wider clines,
      suggesting that the hybrid zone is a semipermeable tension zone. The plumage
      cline was shifted significantly into the genomic background of the orange
      subspecies, consistent with sexual selection driving asymmetrical introgression
      of red plumage alleles across the hybrid zone. This interpretation is supported
      by previous experimental work demonstrating an extra-pair mating advantage for
      red males, but the role of genetic dominance in driving this pattern remains
      unclear. This study highlights the potential for sexual selection to erode
      taxonomic boundaries and promote gene flow, particularly at an intermediate stage
      of divergence. 

PMID- 24889817
TI  - Influences on individuals' decisions to take up the offer of a health check: a
      qualitative study.
AB  - BACKGROUND: Health checks are promoted to evaluate individuals' risk of
      developing disease and to initiate health promotion and disease prevention
      interventions. The NHS Health Check is a cardiovascular risk assessment programme
      introduced in the UK aimed at preventing cardiovascular disease (CVD). Uptake of
      health checks is lower than anticipated. This study aimed to explore influences
      on people's decisions to take up the offer of a health check. METHODS: Semi
      structured interviews were conducted with people registered at four general
      practices in South London. The interview schedule was informed by the Theoretical
      Domains Framework. Data were analysed qualitatively using the Framework method
      using NVivo for data management. RESULTS: Twenty-seven participants invited for a
      health check were included in the study. Seventeen received the health check
      while 10 either did not attend or failed to complete the check. Five themes
      emerging from the data included a lack of awareness of the health check
      programme, beliefs about susceptibility to CVD, beliefs about civic
      responsibility, issues concerning access to appointments, and beliefs about the
      consequences of having a check. CONCLUSIONS: Health check programmes need to
      raise public awareness to ensure that people are informed about the objectives
      and nature of the programme in order to reach an informed decision about taking
      up the invitation. Emphasizing the benefits of prevention and early detection
      might encourage attendance in those who are reluctant to burden the public health
      care systems. Extending outreach initiatives and increasing 'out of hours'
      provision at local community sites could facilitate access.

PMID- 24889819
TI  - Efficacy and safety of endoscopic interventions using the short double-balloon
      endoscope in patients after incomplete colonoscopy.
AB  - BACKGROUND AND AIM: We have previously reported excellent cecal intubation rates
      using a short double-balloon endoscope in patients with a history of incomplete
      colonoscopy. However, data on the endoscopic treatment of colorectal tumors using
      a double-balloon endoscope are limited. The aim of the present study was to
      evaluate the efficacy and safety of endoscopic intervention of colorectal tumors
      using a short double-balloon endoscope. METHODS: We analyzed data from a
      multicenter, prospective study on 110 patients (62 men, median age 66.5 years)
      who underwent total colonoscopy after incomplete colonoscopy to assess the
      characteristics of colorectal tumors, endoscopic interventions, and
      complications. RESULTS: In all, 113 colorectal tumors were detected in 55
      patients; 109 of the tumors were adenomas (24 advanced adenomas) and two each
      were intramucosal and advanced cancers. Locations of the lesions were eight in
      the cecum, 30 in the ascending colon, 18 in the transverse colon, 12 in the
      descending colon, 34 in the sigmoid colon, five in the rectosigmoid and six in
      the rectum. Average tumor diameter was 6.8 +/- 6.3 mm. Fifty-nine polypectomies,
      22 endoscopic mucosal resections, four hot biopsies, and six cold biopsies were
      done. All endoscopic interventions were successfully completed and no
      complications were noted. Two advanced cancers were located in the ascending
      colon and only a double-balloon endoscope could reach them to take a biopsy
      sample. CONCLUSION: Double-balloon endoscopy is effective and safe for endoscopic
      intervention of colorectal tumors, irrespective of the location, in patients
      after incomplete colonoscopy.

PMID- 24889820
TI  - Introduction to propensity scores.
AB  - Although randomization provides a gold-standard method of assessing causal
      relationships, it is not always possible to randomly allocate exposures. Where
      exposures are not randomized, estimating exposure effects is complicated by
      confounding. The traditional approach to dealing with confounding is to adjust
      for measured confounding variables within a regression model for the outcome
      variable. An alternative approach--propensity scoring--instead fits a regression
      model to the exposure variable. For a binary exposure, the propensity score is
      the probability of being exposed, given the measured confounders. These scores
      can be estimated from the data, for example by fitting a logistic regression
      model for the exposure including the confounders as explanatory variables and
      obtaining the estimated propensity scores from the predicted exposure
      probabilities from this model. These estimated propensity scores can then be used
      in various ways-matching, stratification, covariate-adjustment or inverse
      probability weighting-to obtain estimates of the exposure effect. In this paper,
      we provide an introduction to propensity score methodology and review its use
      within respiratory health research. We illustrate propensity score methods by
      investigating the research question: 'Does personal smoking affect the risk of
      subsequent asthma?' using data taken from the Tasmanian Longitudinal Health
      Study.

PMID- 24889821
TI  - Arsenic in drinking water and urinary tract cancers: a systematic review of 30
      years of epidemiological evidence.
AB  - BACKGROUND: Arsenic in drinking water is a public health issue affecting hundreds
      of millions of people worldwide. This review summarizes 30 years of
      epidemiological studies on arsenic exposure in drinking water and the risk of
      bladder or kidney cancer, quantifying these risks using a meta-analytical
      framework. METHODS: Forty studies met the selection criteria. Seventeen provided
      point estimates of arsenic concentrations in drinking water and were used in a
      meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies)
      and kidney cancer mortality (2 studies). Risk estimates for incidence and
      mortality were analyzed separately using Generalized Linear Models. Predicted
      risks for bladder cancer incidence were estimated at 10, 50 and 150 MUg/L arsenic
      in drinking water. Bootstrap randomizations were used to assess robustness of
      effect size. RESULTS: Twenty-eight studies observed an association between
      arsenic in drinking water and bladder cancer. Ten studies showed an association
      with kidney cancer, although of lower magnitude than that for bladder cancer. The
      meta-analyses showed the predicted risks for bladder cancer incidence were 2.7
      [1.2-4.1]; 4.2 [2.1-6.3] and; 5.8 [2.9-8.7] for drinking water arsenic levels of
      10, 50, and 150 MUg/L, respectively. Bootstrapped randomizations confirmed this
      increased risk, but, lowering the effect size to 1.4 [0.35-4.0], 2.3 [0.59-6.4],
      and 3.1 [0.80-8.9]. The latter suggests that with exposures to 50 MUg/L, there
      was an 83% probability for elevated incidence of bladder cancer; and a 74%
      probability for elevated mortality. For both bladder and kidney cancers,
      mortality rates at 150 ug/L were about 30% greater than those at 10 MUg/L.
      CONCLUSION: Arsenic in drinking water is associated with an increased risk of
      bladder and kidney cancers, although at lower levels (<150 MUg/L), there is
      uncertainty due to the increased likelihood of exposure misclassification at the
      lower end of the exposure curve. Meta-analyses suggest exposure to 10 MUg/L of
      arsenic in drinking water may double the risk of bladder cancer, or at the very
      least, increase it by about 40%. With the large number of people exposed to these
      arsenic concentrations worldwide the public health consequences of arsenic in
      drinking water are substantial.

PMID- 24889824
TI  - Identification of an exceptionally short open reading frame in the genome of man,
      encoding a decapeptide, which regulates granulopoiesis by negative feedback.

PMID- 24889822
TI  - Resveratrol-enhanced autophagic flux ameliorates myocardial oxidative stress
      injury in diabetic mice.
AB  - Autophagic dysfunction is observed in diabetes mellitus. Resveratrol has a
      beneficial effect on diabetic cardiomyopathy. Whether the resveratrol-induced
      improvement in cardiac function in diabetes is via regulating autophagy remains
      unclear. We investigated the mechanisms underlying resveratrol-mediated
      protection against heart failure in diabetic mice, with a focus on the role of
      sirtuin 1 (SIRT1) in regulating autophagic flux. Diabetic cardiomyopathy in mice
      was induced by streptozotocin (STZ). Long-term resveratrol treatment improved
      cardiac function, ameliorated oxidative injury and reduced apoptosis in the
      diabetic mouse heart. Western blot analysis revealed that resveratrol decreased
      p62 protein expression and promoted SIRT1 activity and Rab7 expression.
      Inhibiting autophagic flux with bafilomycin A1 increased diabetic mouse mortality
      and attenuated resveratrol-induced down-regulation of p62, but not SIRT1 activity
      or Rab7 expression in diabetic mouse hearts. In cultured H9C2 cells, redundant or
      overactive H2O2 increased p62 and cleaved caspase 3 expression as well as
      acetylated forkhead box protein O1 (FOXO1) and inhibited SIRT1 expression.
      Sirtinol, SIRT1 and Rab7 siRNA impaired the resveratrol amelioration of
      dysfunctional autophagic flux and reduced apoptosis under oxidative conditions.
      Furthermore, resveratrol enhanced FOXO1 DNA binding at the Rab7 promoter region
      through a SIRT1-dependent pathway. These results highlight the role of the
      SIRT1/FOXO1/Rab7 axis in the effect of resveratrol on autophagic flux in vivo and
      in vitro, which suggests a therapeutic strategy for diabetic cardiomyopathy.

PMID- 24889825
TI  - Solid-state dynamics of uranyl polyoxometalates.
AB  - Understanding fundamental uranyl polyoxometalate (POM) chemistry in solution and
      the solid state is the first step to defining its future role in the development
      of new actinide materials and separation processes that are vital to every step
      of the nuclear fuel cycle. Many solid-state geometries of uranyl POMs have been
      described, but we are only beginning to understand their chemical behavior, which
      thus far includes the role of templates in their self-assembly, and the dynamics
      of encapsulated species in solution. This study provides unprecedented detail
      into the exchange dynamics of the encapsulated species in the solid state through
      Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) spectroscopy. Although
      it was previously recognized that capsule-like molybdate and uranyl POMs exchange
      encapsulated species when dissolved in water, analogous exchange in the solid
      state has not been documented, or even considered. Here, we observe the extremely
      high rate of transport of Li(+) and aqua species across the uranyl shell in the
      solid state, a process that is affected by both temperature and pore blocking by
      larger species. These results highlight the untapped potential of emergent f
      block element materials and vesicle-like POMs. 

PMID- 24889826
TI  - Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal
      cancer on surgical and oncologic outcome.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of a longer interval
      between long-course neoadjuvant chemoradiotherapy and surgery on surgical and
      oncologic outcome. METHODS: A total of 233 consecutive patients with clinical
      stage II and III rectal cancer were divided into 2 groups according to the
      neoadjuvant-surgery interval: short-interval group (<= 7 weeks, n = 111), and
      long-interval group (>7 weeks, n = 122). Data on neoadjuvant-surgery interval,
      operative time, perioperative complications, final pathology, disease recurrence,
      and mortality were prospectively collected and analyzed. RESULTS: The two groups
      were comparable in terms of demographics, tumor, and treatment characteristics.
      Operative time and perioperative complications were not influenced by a longer
      interval. Patients in the long-interval group had a significantly higher
      pathologic complete response (pCR) rate (27.1% vs. 15.3%, P = 0.029), and a
      decreased rate of circumferential resection margin involvement (1.6% vs. 8.1%, P
      = 0.020). After a median follow-up of 42 months (range 6-90 months), the 3-year
      local recurrence rate was 12.9% in the short-interval group versus 4.8% in the
      long-interval group (P = 0.025). CONCLUSIONS: A neoadjuvant-surgery interval >7
      weeks is safe and is associated with a higher rate of pCR and R0 resection, and
      decreased local recurrence.

PMID- 24889827
TI  - Concordance and time estimation of store-and-forward mobile teledermatology
      compared to classical face-to-face consultation.
AB  - Smartphones have overcome the limitations of image quality seen in older devices
      and opened a new field of telemedicine called "mobile teledermatology".
      Technological advances and the need to reduce health service costs will strongly
      promote the development of telemedicine. For this reason, we evaluated the
      concordance between store-and-forward mobile teledermatology and the classical
      face-to-face dermatological visit. We also measured the time taken to submit a
      teleconsultation using a smartphone. Before conventional face-to-face visit, a
      final-year resident of the three-year course for general practitioners collected
      medical history, took digital images of skin diseases with a smartphone and,
      measuring the time required to complete this operation, transmitted them to an
      expert teledermatologist. In 391 patients we obtained a concordance between face
      to-face and store-and-forward diagnosis of 91.05% (Cohen kappa coefficient =
      0.906). On average only few minutes needs to be added to a normal visit to
      transmit the cases to an expert teledermatologist. 

PMID- 24889823
TI  - Quantitative mass spectrometric analysis of glycoproteins combined with
      enrichment methods.
AB  - Mass spectrometry (MS) has been a core technology for high sensitive and high
      throughput analysis of the enriched glycoproteome in aspects of quantitative
      assays as well as qualitative profiling of glycoproteins. Because it has been
      widely recognized that aberrant glycosylation in a glycoprotein may involve in
      progression of a certain disease, the development of efficient analysis tool for
      the aberrant glycoproteins is very important for deep understanding about
      pathological function of the glycoprotein and new biomarker development. This
      review first describes the protein glycosylation-targeting enrichment
      technologies mainly employing solid-phase extraction methods such as hydrizide
      capturing, lectin-specific capturing, and affinity separation techniques based on
      porous graphitized carbon, hydrophilic interaction chromatography, or immobilized
      boronic acid. Second, MS-based quantitative analysis strategies coupled with the
      protein glycosylation-targeting enrichment technologies, by using a label-free
      MS, stable isotope-labeling, or targeted multiple reaction monitoring (MRM) MS,
      are summarized with recent published studies.

PMID- 24889828
TI  - Validated context-dependent associations of coronary heart disease risk with
      genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in
      Communities study.
AB  - Markers of the chromosome 9p21 region are regarded as the strongest and most
      reliably significant genome-wide association study (GWAS) signals for Coronary
      heart disease (CHD) risk; this was recently confirmed by the CARDIoGRAMplusC4D
      Consortium meta-analysis. However, while these associations are significant at
      the population level, they may not be clinically relevant predictors of risk for
      all individuals. We describe here the results of a study designed to address the
      question: What is the contribution of context defined by traditional risk factors
      in determining the utility of DNA sequence variations marking the 9p21 region for
      explaining variation in CHD risk? We analyzed a sample of 7,589 (3,869 females
      and 3,720 males) European American participants of the Atherosclerosis Risk in
      Communities study. We confirmed CHD-SNP genotype associations for two 9p21 region
      marker SNPs previously identified by the CARDIoGRAMplusC4D Consortium study, of
      which ARIC was a part. We then tested each marker SNP genotype effect on
      prediction of CHD within sub-groups of the ARIC sample defined by traditional CHD
      risk factors by applying a novel multi-model strategy, PRIM. We observed that the
      effects of SNP genotypes in the 9p21 region were strongest in a sub-group of
      hypertensives. We subsequently validated the effect of the region in an
      independent sample from the Copenhagen City Heart Study. Our study suggests that
      marker SNPs identified as predictors of CHD risk in large population based GWAS
      may have their greatest utility in explaining risk of disease in particular sub
      groups characterized by biological and environmental effects measured by the
      traditional CHD risk factors. 

PMID- 24889829
TI  - Identification of methylation quantitative trait loci (mQTLs) influencing
      promoter DNA methylation of alcohol dependence risk genes.
AB  - Interaction of DNA methylation and sequence variants that are methylation
      quantitative trait loci (mQTLs) may influence susceptibility to diseases such as
      alcohol dependence (AD). We used genome-wide genotype data from 268 African
      Americans (AAs: 129 AD cases and 139 controls) and 143 European Americans (EAs:
      129 AD cases and 14 controls) to identify mQTLs that were associated with
      promoter CpGs in 82 AD risk genes. 282 significant mQTL-CpG pairs (9.9 * 10(-100)
      <= P(nominal) <= 7.7 * 10(-8)) in AAs and 313 significant mQTL-CpG pairs (2.7 *
      10(-53) <= P(nominal) <= 9.9 * 10(-8)) in EAs were identified [i.e., mQTL-CpG
      associations survived multiple-testing correction, q values (false discovery
      rate) <= 0.05]. The most significant mQTL was rs1800759, which was strongly
      associated with CpG cg12011299 in both AAs (P(nominal) = 9.9 * 10(-100); q = 6.7
      * 10(-91)) and EAs (P(nominal) = 2.7 * 10(-53); q = 1.4 * 10(-44)). Rs1800759
      (previously known to be associated to AD) and CpG cg12011299 (distance: 37 bp)
      are both located in alcohol dehydrogenase (ADH) 4 gene (ADH4) promoter region. In
      general, the strength of association between mQTLs and CpGs was inversely
      correlated with the distance between them. Association was also influenced by
      race and AD. Additionally, 48.3 % of the mQTLs identified in AAs and 65.6 % of
      the mQTLs identified in EAs were predicted to be expression QTLs. Three mQTLs
      (rs2173201, rs4147542, and rs4147541 in ADH1B-AHD1C gene cluster region) found in
      AAs were previously identified by our genome-wide association studies as being
      significantly associated with AD in AAs. Thus, DNA methylation, which can be
      influenced by sequence variants and is implicated in gene expression regulation,
      appears to at least partially underlie the association of genetic variation with
      AD.

PMID- 24889831
TI  - Activation of protease-activated receptor-2 disrupts vaginal epithelial barrier
      function.
AB  - The epithelial cell barrier function is a critical factor in the maintenance of
      the homeostasis of the vaginal mucosa. This study elucidates one of the mast cell
      derived chemical mediators, tryptase, on compromising the vaginal epithelial
      barrier function. The results showed that human vaginal cell line, VK2, express
      PAR2. Activation of PAR2 increases the expression of ADAM10 in VK2 cells,
      interferes with the endosome/lysosome fusion, and compromises the epithelial
      barrier function. We conclude that the activation of PAR2 on VK2 cells increases
      the expression of ADAM10, and compromises the VK2 monolayer barrier function. 

PMID- 24889830
TI  - Opposite effects on facial morphology due to gene dosage sensitivity.
AB  - Sequencing technology is increasingly demonstrating the impact of genomic copy
      number variation (CNV) on phenotypes. Opposing variation in growth, head size,
      cognition and behaviour is known to result from deletions and reciprocal
      duplications of some genomic regions. We propose normative inversion of face
      shape, opposing difference from a matched norm, as a basis for investigating the
      effects of gene dosage on craniofacial development. We use dense surface
      modelling techniques to match any face (or part of a face) to a facial norm of
      unaffected individuals of matched age, sex and ethnicity and then we reverse the
      individual's face shape differences from the matched norm to produce the
      normative inversion. We demonstrate for five genomic regions, 4p16.3, 7q11.23,
      11p15, 16p13.3 and 17p11.2, that such inversion for individuals with a
      duplication or (epi)-mutation produces facial forms remarkably similar to those
      associated with a deletion or opposite (epi-)mutation of the same region, and
      vice versa. The ability to visualise and quantify face shape effects of gene
      dosage is of major benefit for determining whether a CNV is the cause of the
      phenotype of an individual and for predicting reciprocal consequences. It enables
      face shape to be used as a relatively simple and inexpensive functional analysis
      of the gene(s) involved. 

PMID- 24889833
TI  - An electrolyte-free flexible electrochromic device using electrostatically strong
      graphene quantum dot-viologen nanocomposites.
AB  - A strong electrostatic MV(2+) -GQD nanocomposite provides an electrolyte-free
      flexible electrochromic device wih high durability. The positively charged MV(2+)
      and negatively charged GQD are strongly stabilized by non-covalent intermolecular
      forces (e.g., electrostatic interactions, pi-pi stacking interactions, and cation
      pi electron interactions), eliminating the need for an electrolyte. An
      electrolyte-free flexible electrochromic device fabricated from the GQD-supported
      MV(2+) exhibits stable performance under mechanical and thermal stresses. 

PMID- 24889832
TI  - Efficient fixation of CO2 by a zinc-coordinated conjugated microporous polymer.
AB  - Zinc-coordinated conjugated microporous polymers (Zn-CMPs), prepared by linking
      salen zinc and 1,3,5-triethynylbenzene, exhibit extraordinary activities
      (turnover frequencies of up to 11600 h(-1) ), broad substrate scope, and group
      tolerance for the synthesis of functional organic carbonates by coupling epoxides
      with CO2 at 120  degrees C and 3.0 MPa without the use of additional solvents.
      The catalytic activity of Zn-CMP is comparable to those of homogeneous catalysts
      and superior to those of other heterogeneous catalysts. This catalyst could be
      reused more than ten times without a significant decrease in performance.

PMID- 24889835
TI  - Adaptation and validation of the Ankylosing Spondylitis Work Instability Scale
      (AS-WIS) for use in Turkey.
AB  - The Ankylosing Spondylitis Work Instability Scale (AS-WIS) is a recently
      developed 20-item measure to assess work instability in AS. This study aimed to
      adapt the AS-WIS to Turkish and to test its reliability and validity. After the
      translation process, 132 AS patients were assessed by the AS-WIS, Bath AS Disease
      Activity Index, Bath AS Functional Index and the AS Quality of Life
      Questionnaire. Reliability was tested by internal consistency, person separation
      index (PSI) and intra-class correlation coefficient (ICC); internal construct
      validity by Rasch analysis; external construct validity by associations with
      comparator scales and cross-cultural validity by comparison with the original UK
      data. Reliability of the Turkish AS-WIS was good with Cronbach's alpha and PSI of
      0.88 and test-retest ICC of 0.91. Data showed good fit to Rasch model [mean item
      fit: -0.477 (SD 1.047), Chi-square interaction: 60.9 (df = 40, p = 0.018)]. There
      was no differential item functioning by age, gender, disease duration or work
      type. The scale was strictly unidimensional. 51 % of the patients were at
      moderate risk, and 9 % were at high risk of having to give up their work.
      External construct validity was confirmed by expected correlations with
      comparator scales, and a clear gradient of disease activity and functional status
      across increasing levels of risk. Cross-cultural validity showed some differences
      in item locations, but this cancelled out at the test level. Turkish version of
      the AS-WIS is reliable, valid and available for use in routine clinical setting
      to identify patients who are at risk of having to give up their current job.

PMID- 24889837
TI  - Impact of a standardized training program on midwives' ability to assess fetal
      heart anatomy by ultrasound.
AB  - BACKGROUND: Studies of prenatal detection of congenital heart disease (CHD) in
      the UK, Italy, and Norway indicate that it should be possible to improve the
      prenatal detection rate of CHD in Sweden. These studies have shown that training
      programs, visualization of the outflow tracts and color-Doppler all can help to
      speed up and improve the detection rate and accuracy. We aimed to introduce a
      more accurate standardized fetal cardiac ultrasound screening protocol in Sweden.
      METHODS: A novel pedagogical model for training midwives in standardized cardiac
      imaging was developed, a model using a think-aloud analysis during a pre- and
      post-course test and a subsequent group reflection. The self-estimated
      difficulties and knowledge gaps of two experienced and two beginner midwives were
      identified. A two-day course with mixed lectures, demonstrations and hands-on
      sessions was followed by a feedback session three months later consisting of an
      interview and check-up. The long-term effects were tested two years later.
      RESULTS: At the post-course test the self-assessed uncertainty was lower than at
      the pre-course test. The qualitative evaluation showed that the color Doppler
      images were difficult to interpret, but the training seems to have improved their
      ability to use the new technique. The ability to perform the method remained at
      the new level at follow-up both three months and two years later. CONCLUSIONS:
      Our results indicate that by implementing new imaging modalities and providing
      hands-on training, uncertainty can be reduced and examination time decreased, but
      they also show that continuous on-site training with clinical and technical back
      up is important.

PMID- 24889838
TI  - Subcutaneous pharmacokinetics of the cardiac hormone vessel dilator.
AB  - Vessel dilator, a hormone synthesized in the heart, eliminates 71% of human small
      cell lung cancers and 67% of human breast cancers growing in mice when given
      subcutaneously (s.c.) via osmotic pumps. The pharmacokinetics of s.c.
      administered vessel dilator have not been evaluated previously. In the present
      study, the pharmacokinetics of vessel dilator following s.c. bolus (ScB) or 3 h
      s.c. infusion (ScI) were compared with those following i.v. bolus (IvB)
      administration in male Fischer 344 rats. The half-life (t1/2 ) of vessel dilator
      after ScI, IvB and ScB was 54, 43 and 30 min, respectively. The tmax for vessel
      dilator after IvB, ScB and ScI administration was 1.5, 23 and 156 min,
      respectively, whereas the corresponding Cmax values were 3749, 887 and 471 ng/L
      (normalized against the dose used for ScB and IvB). The area under the curve
      (AUC0-infinity ) for vessel dilator was 1166, 880 and 1652 ng h/mL (normalized)
      following IvB, ScB and ScI administration, respectively. The volume of
      distribution for vessel dilator was 2.38, 0.92 and 1.08 L following IvB, ScB and
      SCI administration, respectively; corresponding clearance values were 1.69, 1.50
      and 0.78 L/h, respectively. Plasma concentrations of vessel dilator after each of
      the three methods of administration mirrored their predicted concentration-time
      profiles. We conclude that vessel dilator administered via ScI has a
      significantly greater AUC and t1/2 and slowed clearance compared with IvB or ScB
      administration (P < 0.001), suggesting that s.c. infusion is the preferred method
      of administration, based on pharmacokinetics, to treat cancers. 

PMID- 24889839
TI  - Clinical presentation and patterns of care for short-term survivors of malignant
      glioma.
AB  - Palliative care provision for patients with high-grade malignant glioma is often
      under-utilised. Difficulties in prognostication and inter-patient variability in
      survival may limit timely referral. This study sought to (1) describe the
      clinical presentation of short-term survivors of malignant glioma (survival time
      <120 days); (2) map their hospital utilisation, including palliative and
      supportive care service use, and place of death; (3) identify factors which may
      be important to serve as a prompt for palliative care referral. A retrospective
      cohort study of incident malignant glioma cases between 2003-2009 surviving <120
      days in Victoria, Australia was undertaken (n = 482). Cases were stratified
      according to the patient's survival status (dead vs. alive) at the end of the
      diagnosis admission, and at 120 days from diagnosis. Palliative care was received
      by 78 % of patients who died during the diagnosis admission. Only 12 % of
      patients who survived the admission and then deteriorated rapidly dying in the
      following 120 days were referred to palliative care in their hospital admission,
      suggesting an important clinical subgroup that may miss out on being linked into
      palliative care services. The strongest predictor of death during the diagnosis
      admission was the presence of cognitive or behavioural symptoms, which may be an
      important prompt for early palliative care referral.

PMID- 24889843
TI  - Comparing accuracy of knowledge of functional effects of schizophrenia and brain
      injury.
AB  - This study developed and validated the Brain Injury and Schizophrenia Awareness
      Scale (BISAS) to compare accuracy of knowledge of functional effects of
      schizophrenia and TBI. The BISAS displayed good internal consistency and evidence
      of construct validity. Overall, general community participants (n=143) lacked
      understanding of the shared effects of these conditions, and attributed emotional
      and behavioural deficits to schizophrenia and cognitive deficits to TBI. 

PMID- 24889844
TI  - Eating disorder symptoms among Japanese female students in 1982, 1992 and 2002.
AB  - To study transcultural differences in eating disorders, we examined eating
      disorder symptoms and point prevalence of eating disorders among Japanese female
      students in 1982, 1992 and 2002. In 1982, 1992 and 2002, a total of 10,499
      Japanese female students, aged 16-23 years, were asked to complete a self
      administered questionnaire. Diagnosis of an eating disorder was made on the basis
      of DSM-IV criteria. On almost all measures, there were significant increases of a
      disordered attitude about fear of gaining weight, body perception disturbance and
      problematic eating behaviors over time. The point prevalence of anorexia nervosa,
      bulimia nervosa and eating disorder not otherwise specified significantly
      increased over time. These results suggest that the prevalence of eating disorder
      symptoms and the point prevalence of eating disorders were increasing among
      Japanese female students in 2002. Changing socio-cultural factors in Japan may
      explain the dramatic increase of eating disorders over time. 

PMID- 24889836
TI  - Sleep-wake disturbances in sedentary community-dwelling elderly adults with
      functional limitations.
AB  - OBJECTIVES: To evaluate sleep-wake disturbances in sedentary community-dwelling
      elderly adults with functional limitations. DESIGN: Cross-sectional. SETTING:
      Lifestyle Interventions and Independence in Elder (LIFE) Study. PARTICIPANTS:
      Community-dwelling persons (mean age 78.9) who spent fewer than 20 min/wk in the
      previous month engaged in regular physical activity and fewer than 125 min/wk of
      moderate physical activity, and had a Short Physical Performance Battery (SPPB)
      score of <10 (N = 1,635). MEASUREMENTS: Mobility was evaluated according to 400-m
      walk time (slow gait speed defined as <0.8 m/s) and SPPB score (<= 7 defined
      moderate to severe mobility impairment). Physical inactivity was defined
      according to sedentary time, as a percentage of accelerometry wear time with
      activity of <100 counts/min; participants in the top quartile of sedentary time
      were classified as having a high sedentary time. Sleep-wake disturbances were
      evaluated using the Insomnia Severity Index (ISI) (range 0-28; >= 8 defined
      insomnia), Epworth Sleepiness Scale (ESS) (range 0-24; >= 10 defined daytime
      drowsiness), Pittsburgh Sleep Quality Index (PSQI) (range 0-21; >5 defined poor
      sleep quality), and Berlin Questionnaire (high risk of sleep apnea). RESULTS:
      Prevalence rates were 43.5% for slow gait speed and 44.7% for moderate to severe
      mobility impairment, with 77.0% of accelerometry wear time spent as sedentary
      time. Prevalence rates were 33.0% for insomnia, 18.1% for daytime drowsiness,
      47.8% for poor sleep quality, and 32.9% for high risk of sleep apnea.
      Participants with insomnia had a mean ISI score of 12.1, those with daytime
      drowsiness had a mean ESS score of 12.5, and those with poor sleep quality had a
      mean PSQI score of 9.2. In adjusted models, measures of mobility and physical
      inactivity were generally not associated with sleep-wake disturbances, using
      continuous or categorical variables. CONCLUSION: In a large sample of sedentary
      community-dwelling elderly adults with functional limitations, sleep-wake
      disturbances were prevalent but only mildly severe and were generally not
      associated with mobility impairment or physical inactivity.

PMID- 24889842
TI  - Comparing perceived public stigma and personal stigma of mental health treatment
      seeking in a young adult sample.
AB  - Perceived public stigma regarding seeking mental health treatment can be a
      barrier to accessing services for young adults. While factors associating with
      personal stigma regarding how one would view and treat others have been
      identified, the discrepancies between perceived and personal stigma have received
      less research attention. We designed the current study to expand on previous
      research and examine the discrepancies between perceived public stigma and
      personal stigma among a sample of 386 primarily White and Asian college students.
      Participants completed surveys of mental health symptoms, treatment experience
      and attitudes, perceived public, and personal stigma. Overall, participants
      generally reported greater perceived public stigma than personal stigma; an
      effect that was particularly evident for women and those with mental health
      symptoms. The majority of participants disagreed with items assessing personal
      stigma. Negative attitudes toward treatment and anxiety symptoms associated with
      perceived public stigma, while male gender, Asian ethnicity, and negative
      attitudes toward treatment associated with personal stigma. Findings have
      implications for interventions and marketing programs to help change perceptions
      about mental health stigma to encourage utilization of services for those young
      people who could benefit from care. 

PMID- 24889846
TI  - Schizotypal personality questionnaire: new sources of validity evidence in
      college students.
AB  - Schizotypal traits represent the behavioral expression of vulnerability to
      psychosis in general population. Among the most widely used measurement
      instruments, we could find the Schizotypal Personality Questionnaire (SPQ)
      (Raine, 1991). However, some aspects of its psychometric quality have yet to be
      analyzed. The main goal of the present study was to gather new sources of
      validity evidence of the SPQ scores in non-clinical young adults. The final
      sample was made up of 1123 college students (M=20.3 years; S.D.=2.6). The study
      of the internal structure using exploratory factor analysis revealed that SPQ
      items were grouped in a theoretical structure of seven second-order factors.
      Confirmatory factor analyses showed that the four-factor model (Paranoid)
      displayed better goodness-of-fit indices than the other hypothetical dimensional
      models tested. More complex measurement models, such as those tested using second
      order confirmatory factor analyses and Exploratory Structural Equation Modeling,
      also showed adequate goodness-of-fit indices. The reliability of the SPQ scores
      ranged from 0.80 to 0.91. A total of 11 items showed differential functioning by
      gender. Advances in psychosis phenotype measurement open up new horizons to
      understand the structure and content of schizotypy. 

PMID- 24889845
TI  - Bilateral vs. unilateral repetitive transcranial magnetic stimulation in treating
      major depression: a meta-analysis of randomized controlled trials.
AB  - Previous studies have demonstrated inconsistent findings regarding the efficacy
      of bilateral vs. unilateral repetitive transcranial magnetic stimulation (rTMS)
      in treating major depressive disorder (MDD). Therefore, this meta-analysis was
      conducted to compare the efficacy of these two rTMS modalities. Data were
      obtained from seven randomized controlled trials (RCTs) consisting of 509
      subjects. Bilateral and unilateral rTMS displayed comparable efficacy in treating
      MDD with a pooled odds ratios of 1.06 (95% confidence interval (CI)=0.58-1.91)
      for response rates and 1.05 (95% CI=0.52-2.11) for remission rates. Subgroup
      analysis found that bilateral rTMS was equally effective in comparison with both
      left and right unilateral rTMS. No significant differences in drop-out rates were
      found. No publication bias was detected. In conclusion, the pooled examination
      demonstrated that bilateral rTMS displays comparable anti-depressant efficacy and
      acceptability to unilateral rTMS in treating MDD. These findings suggest that
      simultaneous rTMS of the right and left dorsolateral prefrontal cortices in MDD
      patients does not provide marginal benefits in terms of efficacy or
      acceptability. As the number of RCTs included here was limited, further large
      scale multi-center RCTs are required to validate our conclusions. 

PMID- 24889847
TI  - Association between COMT Val158Met genotype and EEG alpha peak frequency tested
      in two independent cohorts.
AB  - This study could not confirm the association between the Catechol-O
      Methyltransferase Val158Met polymorphism (COMT) and electroencephalographic (EEG)
      alpha peak frequency (APF) in two independent cohorts of 187 (96 depressed and 91
      healthy participants) and 413 healthy participants. If COMT and APF play a role
      in depression or antidepressant treatment response, they do not have a shared
      pathway. We emphasize the importance of publishing null-findings for obtaining
      more accurate overall estimates of genetic effects. 

PMID- 24889848
TI  - Systematic review and network meta-analysis comparing antithrombotic agents for
      the prevention of stroke and major bleeding in patients with atrial fibrillation.
AB  - OBJECTIVE: To examine the comparative efficacy and safety of antithrombotic
      treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists
      (VKA) at a standard adjusted dose (target international normalised ratio 2.0
      3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial
      fibrillation and among subpopulations. DESIGN: Systematic review and network meta
      analysis. DATA SOURCES: A systematic literature search strategy was designed and
      carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and
      the grey literature including the websites of regulatory agencies and health
      technology assessment organisations for trials published in English from 1988 to
      January 2014. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled
      trials were selected for inclusion if they were published in English, included at
      least one antithrombotic treatment and involved patients with non-valvular atrial
      fibrillation eligible to receive anticoagulant therapy. RESULTS: For stroke or
      systemic embolism, dabigatran 150 mg and apixaban twice daily were associated
      with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and
      the combination of clopidogrel plus low-dose ASA were associated with increases.
      Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for
      dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For
      major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and
      dabigatran 110 mg twice daily were associated with reductions compared to
      standard adjusted dose VKA. Absolute risk reductions with these agents ranged
      from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24
      more for medium dose ASA. CONCLUSIONS: Compared with standard adjusted dose VKA,
      new oral anticoagulants were associated with modest reductions in the absolute
      risk of stroke and major bleeding. People on antiplatelet drugs experienced more
      strokes compared with anticoagulant drugs without any reduction in bleeding risk.
      To fully elucidate the comparative benefits and harms of antithrombotic agents
      across the various subpopulations, rigorously conducted comparative studies or
      network meta-regression analyses of patient-level data are required. SYSTEMATIC
      REVIEW REGISTRATION NUMBER: PROSPERO registry-CRD42012002721.

PMID- 24889850
TI  - Awareness of occupational hazards and use of safety measures among welders: a
      cross-sectional study from Eastern Nepal.
AB  - OBJECTIVE: The proper use of safety measures by welders is an important way of
      preventing and/or reducing a variety of health hazards that they are exposed to
      during welding. There is a lack of knowledge about hazards and personal
      protective equipments (PPEs) and the use of PPE among the welders in Nepal is
      limited. We designed a study to assess welders' awareness of hazards and PPE, and
      the use of PPE among the welders of eastern Nepal and to find a possible
      correlation between awareness and use of PPE among them. MATERIALS AND METHODS: A
      cross-sectional study of 300 welders selected by simple random sampling from
      three districts of eastern Nepal was conducted using a semistructured
      questionnaire. Data regarding age, education level, duration of employment,
      awareness of hazards, safety measures and the actual use of safety measures were
      recorded. RESULTS: Overall, 272 (90.7%) welders were aware of at least one hazard
      of welding and a similar proportion of welders were aware of at least one PPE.
      However, only 47.7% used one or more types of PPE. Education and duration of
      employment were significantly associated with the awareness of hazards and of PPE
      and its use. The welders who reported using PPE during welding were two times
      more likely to have been aware of hazards (OR=2.52, 95% CI 1.09 to 5.81) and five
      times more likely to have been aware of PPE compared with the welders who did not
      report the use of PPE (OR=5.13, 95% CI 2.34 to 11.26). CONCLUSIONS: The welders
      using PPE were those who were aware of hazards and PPE. There is a gap between
      being aware of hazards and PPE (90%) and use of PPE (47%) at work. Further
      research is needed to identify the underlying factors leading to low utilisation
      of PPE despite the welders of eastern Nepal being knowledgeable of it.

PMID- 24889849
TI  - Impact of lifetime opioid exposure on arterial stiffness and vascular age: cross
      sectional and longitudinal studies in men and women.
AB  - OBJECTIVE: To characterise and compare the potentiation of arterial stiffness and
      vascular ageing by opioids in men and women. DESIGN: Cross-sectional and
      longitudinal studies of 576 clinical controls and 687 opioid-dependent patients
      (ODP) on 710 and 1305 occasions, respectively, over a total of 2382 days (6.52
      years), 2006-2011. Methodology Radial pulse wave analysis with Atcor SphygmoCor
      system (Sydney). SETTING: Primary care. PARTICIPANTS:  CONTROLS: General practice
      patients with non-cardiovascular disorders, and university student controls. ODP:
      Patients undergoing clinical management of their opioid dependence. CONTROLS had
      lower chronological ages (CAs) than ODP (30.0+/-0.5 vs 34.5+/-0.3, mean+/-SEM,
      p<0.0001). 69.6% and 67.7% participants were men, and 16% and 92.3% were smokers
      (p<0.0001) for controls and ODP, respectively. 86.3%, 10.3% and 3.4% of ODP were
      treated with buprenorphine (6.98+/-0.21 mg), methadone (63.04+/-4.01 mg) or
      implant naltrexone, respectively. Body mass index (BMI) was depressed in ODP.
      INTERVENTIONS: Nil. PRIMARY OUTCOME MEASURES: Vascular Reference Age (RA) and the
      ratio of vascular age to chronological age (RA/CA). SECONDARY OUTCOME MEASURES:
      Arterial stiffness including Augmentation Index. RESULTS: After BMI adjustment,
      RA in ODP was higher as a function of CA and of time (both p<0.05). Modelled mean
      RA in control and ODP was 35.6 and 36.3 years (+1.97%) in men, and 34.5 and 39.2
      years (+13.43%) in women, respectively. Changes in RA and major arterial
      stiffness indices were worse in women both as a factor (p = 0.0036) and in
      interaction with CA (p = 0.0040). Quadratic, cubic and quartic functions of
      opioid exposure duration outperformed linear models with RA/CA over CA and over
      time. The opioid dose-response relationship persisted longitudinally after
      multiple adjustments from p=0.0013 in men and p=0.0073 in women. CONCLUSIONS:
      Data show that lifetime opioid exposure, an interactive cardiovascular risk
      factor, particularly in women, is related to linear, quadratic, cubic and quartic
      functions of treatment duration and is consistent with other literature of
      accelerated ageing in patients with OD.

PMID- 24889851
TI  - Spatial inequalities in life expectancy within postindustrial regions of Europe:
      a cross-sectional observational study.
AB  - OBJECTIVES: To compare spatial inequalities in life expectancy (LE) in West
      Central Scotland (WCS) with nine other postindustrial European regions. DESIGN: A
      cross-sectional observational study. SETTING: WCS and nine other postindustrial
      regions across Europe. PARTICIPANTS: Data for WCS and nine other comparably
      deindustrialised European regions were analysed. Male and female LEs at birth
      were obtained or calculated for the mid-2000s for 160 districts within selected
      regions. Districts were stratified into two groups: small (populations of between
      141 000 and 185 000 people) and large (populations between 224 000 and 352 000).
      The range and IQR in LE were used to describe within-region disparities. RESULTS:
      In small districts, the male LE range was widest in WCS and Merseyside, while the
      IQR was widest in WCS and Northern Ireland. For women, the LE range was widest in
      WCS, though the IQR was widest in Northern Ireland and Merseyside. In large
      districts, the range and IQR in LE was widest in WCS and Wallonia for both sexes.
      CONCLUSIONS: Subregional spatial inequalities in LE in WCS are wide compared with
      other postindustrial mainland European regions, especially for men. Future
      research could explore the contribution of economic, social and political factors
      in reducing these inequalities.

PMID- 24889852
TI  - Prediction of liver disease in patients whose liver function tests have been
      checked in primary care: model development and validation using population-based
      observational cohorts.
AB  - OBJECTIVE: To derive and validate a clinical prediction model to estimate the
      risk of liver disease diagnosis following liver function tests (LFTs) and to
      convert the model to a simplified scoring tool for use in primary care. DESIGN:
      Population-based observational cohort study of patients in Tayside Scotland
      identified as having their LFTs performed in primary care and followed for 2
      years. Biochemistry data were linked to secondary care, prescriptions and
      mortality data to ascertain baseline characteristics of the derivation cohort. A
      separate validation cohort was obtained from 19 general practices across the rest
      of Scotland to externally validate the final model. SETTING: Primary care,
      Tayside, Scotland. PARTICIPANTS: Derivation cohort: LFT results from 310 511
      patients. After exclusions (including: patients under 16 years, patients having
      initial LFTs measured in secondary care, bilirubin >35 MUmol/L, liver
      complications within 6 weeks and history of a liver condition), the derivation
      cohort contained 95 977 patients with no clinically apparent liver condition.
      Validation cohort: after exclusions, this cohort contained 11 653 patients.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Diagnosis of a liver condition within 2
      years. RESULTS: From the derivation cohort (n=95 977), 481 (0.5%) were diagnosed
      with a liver disease. The model showed good discrimination (C-statistic=0.78).
      Given the low prevalence of liver disease, the negative predictive values were
      high. Positive predictive values were low but rose to 20-30% for high-risk
      patients. CONCLUSIONS: This study successfully developed and validated a clinical
      prediction model and subsequent scoring tool, the Algorithm for Liver Function
      Investigations (ALFI), which can predict liver disease risk in patients with no
      clinically obvious liver disease who had their initial LFTs taken in primary
      care. ALFI can help general practitioners focus referral on a small subset of
      patients with higher predicted risk while continuing to address modifiable liver
      disease risk factors in those at lower risk.

PMID- 24889853
TI  - Criminalisation of clients: reproducing vulnerabilities for violence and poor
      health among street-based sex workers in Canada-a qualitative study.
AB  - OBJECTIVES: To explore how criminalisation and policing of sex buyers (clients)
      rather than sex workers shapes sex workers' working conditions and sexual
      transactions including risk of violence and HIV/sexually transmitted infections
      (STIs). DESIGN: Qualitative and ethnographic study triangulated with sex work
      related violence prevalence data and publicly available police statistics.
      SETTING: Vancouver, Canada, provides a unique opportunity to evaluate the impact
      of policies that criminalise clients as the local police department adopted a sex
      work enforcement policy in January 2013 that prioritises sex workers' safety over
      arrest, while continuing to target clients. PARTICIPANTS: 26 cisgender and 5
      transgender women who were street-based sex workers (n=31) participated in
      semistructured interviews about their working conditions. All had exchanged sex
      for money in the previous 30 days in Vancouver. OUTCOME MEASURES: Thematic
      analysis of interview transcripts and ethnographic field notes focused on how
      police enforcement of clients shaped sex workers' working conditions and sexual
      transactions, including risk of violence and HIV/STIs, over an 11-month period
      postpolicy implementation (January-November 2013). RESULTS: Sex workers'
      narratives and ethnographic observations indicated that while police sustained a
      high level of visibility, they eased charging or arresting sex workers and showed
      increased concern for their safety. However, participants' accounts and police
      statistics indicated continued police enforcement of clients. This profoundly
      impacted the safety strategies sex workers employed. Sex workers continued to
      mistrust police, had to rush screening clients and were displaced to outlying
      areas with increased risks of violence, including being forced to engage in
      unprotected sex. CONCLUSIONS: These findings suggest that criminalisation and
      policing strategies that target clients reproduce the harms created by the
      criminalisation of sex work, in particular, vulnerability to violence and
      HIV/STIs. The current findings support decriminalisation of sex work to ensure
      work conditions that support the health and safety of sex workers in Canada and
      globally.

PMID- 24889855
TI  - Switchable reconfiguration of an interlocked DNA olympiadane nanostructure.
AB  - Interlocked DNA rings (catenanes) are interesting reconfigurable nanostructures.
      The synthesis of catenanes with more than two rings is, however, hampered, owing
      to low yields of these systems. We report a new method for the synthesis of
      catenanes with a controlled number of rings in satisfactory yields. Our approach
      is exemplified by the synthesis of a five-ring DNA catenane that exists in four
      different configurations. By the use of nucleic acids as "fuels" and "antifuels",
      the cyclic reconfiguration of the system across four states is demonstrated. One
      of the states, olympiadane, corresponds to the symbol of the Olympic Games. The
      five-ring catenane was implemented as a mechanical scaffold for the
      reconfiguration of Au NPs. The advantages of DNA catenanes over supramolecular
      catenanes include the possibility of generating highly populated defined states
      and the feasibility of tethering nanoobjects to the catenanes, which act as a
      mechanical scaffold to reconfigure the nanoobjects. 

PMID- 24889854
TI  - Pain education to prevent chronic low back pain: a study protocol for a
      randomised controlled trial.
AB  - INTRODUCTION: Low back pain (LBP) is the leading cause of disability worldwide.
      Of those patients who present to primary care with acute LBP, 40% continue to
      report symptoms 3 months later and develop chronic LBP. Although it is possible
      to identify these patients early, effective interventions to improve their
      outcomes are not available. This double-blind (participant/outcome assessor)
      randomised controlled trial will investigate the efficacy of a brief educational
      approach to prevent chronic LBP in 'at-risk' individuals. METHODS/ANALYSIS:
      Participants will be recruited from primary care practices in the Sydney
      metropolitan area. To be eligible for inclusion participants will be aged 18-75
      years, with acute LBP (<4 weeks' duration) preceded by at least a 1 month pain
      free period and at-risk of developing chronic LBP. Potential participants with
      chronic spinal pain and those with suspected serious spinal pathology will be
      excluded. Eligible participants who agree to take part will be randomly allocated
      to receive 2*1 h sessions of pain biology education or 2*1 h sessions of sham
      education from a specially trained study physiotherapist. The study requires 101
      participants per group to detect a 1-point difference in pain intensity 3 months
      after pain onset. Secondary outcomes include the incidence of chronic LBP,
      disability, pain intensity, depression, healthcare utilisation, pain attitudes
      and beliefs, global recovery and recurrence and are measured at 1 week post
      intervention, and at 3, 6 and 12 months post LBP onset. ETHICS/DISSEMINATION:
      Ethical approval was obtained from the University of New South Wales Human Ethics
      Committee in June 2013 (ref number HC12664). Outcomes will be disseminated
      through publication in peer-reviewed journals and presentations at international
      conference meetings. TRIAL REGISTRATION NUMBER:
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261200118080
      .

PMID- 24889857
TI  - Rapid on-site evaluation has high diagnostic yield differentiating adenocarcinoma
      vs squamous cell carcinoma of non-small cell lung carcinoma, not otherwise
      specified subgroup.
AB  - Our objective was to evaluate the diagnostic yield of rapid on-site evaluation
      (ROSE) on the differential diagnosis of non-small cell lung carcinoma, not
      otherwise specified (NSCLC-NOS). Biopsied cases diagnosed as NSCLC-NOS with ROSE
      during 2004 through 2008 were retrieved. Diagnostic confirmation was done with
      immunohistochemistry (IHC) involving thyroid transcription factor-1 and p63
      immunostains. For the study, 106 cases were available. The final diagnoses
      rendered were squamous cell carcinoma (SqCC) (n = 39) and adenocarcinoma (AC) (n
      = 67). Cytologic, histologic, and IHC concordance for these diagnoses occurred in
      75 cases (70.8 %), of which 56 (52.8%) were AC and 19 (17.9%) were SqCC.
      Cytologic, histologic, and IHC discordance was found in 31 cases (29.2%). Of
      these 31 cases, 11 NSCLC-NOS diagnoses histologically corresponded to 1 SqCC plus
      4 ACs, and 4 favor SqCC plus 2 ACs; the former 5 NSCLC-NOS cases classified
      correctly through cytology, as well as IHC. However, IHC was not available for
      the latter 6 NSCLC-NOS cases that were also classified correctly through
      cytology. In addition, only 3 NSCLC-NOS diagnoses cytologically corresponded to 3
      favor SqCC histologically, in which IHC was not available, and for 2 cases that
      both corresponded to favor SqCC and favor AC histologically and cytologically. In
      the other 15 cases, histology labeled 4 cases NSCLC-NOS and misclassified 2
      cases; cytology labeled 1 case NSCLC-NOS and misclassified 13 cases. ROSE has
      high diagnostic yield over subclassification of NSCLC-NOS. We recommend
      allocating a cytotechnologist for specimen adequacy and a cytopathologist for
      cytologic diagnosis.

PMID- 24889858
TI  - Diagnosis and preoperative imaging of multiple endocrine neoplasia type 2:
      current status and future directions.
AB  - Multiple endocrine neoplasia type 2 (MEN2) is a rare autosomal dominant syndrome
      caused by mutations in the RET protooncogene and is characterized by a strong
      penetrance of medullary thyroid carcinoma (all subtypes) and is often accompanied
      by pheochromocytoma (MEN2A/2B) and primary hyperparathyroidism (MEN2A). The
      evaluation and management of MEN2-related tumours is often different from that of
      sporadic counterparts. This review article provides an overview of clinical
      manifestations, diagnosis and surgical management of MEN2 patients. This review
      also presents applications of the most up-to-date imaging modalities to MEN2
      patients that are tightly linked to the clinical management and aims to guide
      physicians towards a rationale for the use of imaging prior to prophylactic
      thyroidectomy, initial surgery and reoperations for persistent/recurrent disease.
      This review also concludes that, in the near future, it is expected that these
      patients will indeed benefit from newly developed positron emission tomography
      approaches which will target peptide receptors and protein kinases.
      Identification of MEN2-specific radiopharmaceuticals will also soon arise from
      molecular profiling studies. Furthermore, subtotal (cortical-sparing)
      adrenalectomy, which is a valid option in MEN2 for avoiding long-term steroid
      replacement, will benefit from an accurate estimation through imaging of
      differential adrenocortical function. 

PMID- 24889859
TI  - A pediatric prognostic score for patients undergoing allogeneic hematopoietic
      stem cell transplantation.
AB  - PURPOSE: The purpose of this study was to find and evaluate risk factors
      influencing the outcome of allogeneic hematopoietic stem cell transplantation
      (HSCT) in children and to develop a score stratifying patients by their risk of
      mortality. METHODS: We retrospectively analyzed the effects of patient and donor
      characteristics as well as laboratory data including liver, iron, and
      inflammation parameters on the overall survival of 131 children and young adults
      with malignant and non-malignant diseases undergoing allogeneic HSCT. RESULTS: In
      univariate analysis, 5-yr overall survival decreased significantly in patients
      with high disease risk (38% vs. 74%, P < 0.001), peripheral blood as graft source
      (47% vs. 73% for bone marrow, P < 0.001), ferritin >1500 ng/mL (41% vs. 79%, P =
      0.001), C-reactive protein >10 mg/L (55% vs. 69%, P = 0.019), lactate
      dehydrogenase >6 MUm?s (22% vs. 67%, P = 0.001), gamma-glutamyl transpeptidase >1
      MUm?s (43% vs. 68%, P = 0.035), and cholinesterase <60 MUm?s (36% vs. 70%, P =
      0.002). For HLA recipient-donor match, there was a 5-yr overall survival of 81%
      for matched related, 58% for matched unrelated, 56% for mismatched unrelated, and
      50% for haploidentical related donors (P = 0.020). We subsequently developed a
      score of parameters significant in multivariate analysis, that is, disease risk
      (HR = 4.1, P = 0.027), ferritin (HR = 6.4, P = 0.002), and cholinesterase (HR =
      5.3, P = 0.027). For this score, 5-yr overall survival was 92% for the low-risk
      group, 66% for the intermediate-risk group, and 17% for the high-risk group (P <
      0.001). CONCLUSIONS: Disease risk, ferritin, and cholinesterase are factors
      decisively influencing the prognosis after HSCT and should be evaluated in
      further trials.

PMID- 24889860
TI  - The impact of rural health care accessibility on cancer-related behaviors and
      outcomes.
AB  - BACKGROUND: This research seeks to identify the relationship between economic
      factors related to the ability to receive and pay for health services and adverse
      cancer outcomes, as well as preventative screening and behavioral factors that
      influence the risk of cancer. We focus on the Northern High Plains region, where
      we are able to compare regions with extremely low access to health services with
      those with relatively high levels of access. OBJECTIVE: This study aims to
      identify health disparities in rural communities, particularly among Native
      American populations, and, thereby, begin to determine the most effective means
      by which to deliver health services to areas where geography, economics, and
      culture might prevent traditional models of health delivery from providing
      sufficient incentives for the prevention of adverse cancer-related outcomes.
      METHODS: The Health Care Accessibility Index (HCAI) is computed through the use
      of principal component analysis and includes economic variables as well as
      variables concerning institutional and geographic access to health care. Index
      values are then regressed onto cancer outcomes, cancer-prevention outcomes, and
      cancer-related risk, using weighted least squares and quantile regressions.
      RESULTS: Counties with relatively poor access to health care (low HCAI) also have
      statistically (1) lower breast cancer screening rates, (2) higher smoking
      prevalence, (3) higher obesity prevalence, and (4) higher cancer-related
      mortality rates. Breast cancer screening is found to be especially sensitive to
      areas of low health accessibility. CONCLUSIONS: Empirical results provide support
      for policy efforts to increase the accessibility of health care services that are
      targeted to areas with low mammography screening rates, high obesity rates, high
      smoking prevalence, as well as areas near Native American reservation
      territories.

PMID- 24889861
TI  - Globalization of Chikungunya: 10 years to invade the world.

PMID- 24889862
TI  - Novel ANO5 homozygous microdeletion causing myalgia and unprovoked rhabdomyolysis
      in an Arabic man.
AB  - INTRODUCTION: Recessive mutations in the anoctamin-5 gene (ANO5) cause a spectrum
      of clinical phenotypes, including limb-girdle muscular dystrophy (LGMD 2L),
      distal myopathy, and asymptomatic hyperCKemia. METHODS: In this report we
      describe our clinical, electrophysiological, pathological, and molecular findings
      in a subject with anoctaminopathy-5. RESULTS: A 49-year-old Arabic man from a
      consanguineous family presented with a 5-year history of myalgias, hyperCKemia
      and an episode of unprovoked rhabdomyolysis. Muscle biopsy showed mild myopathic
      changes and interstitial amyloid deposition. ANO5 analysis detected a novel
      homozygous deletion of approximately 11.9 kb encompassing exons 13-17, predicted
      to be pathogenic. CONCLUSIONS: Anoctaminopathy-5 can manifest with a phenotype
      reminiscent of metabolic myopathy and should be considered as a potential cause
      of myalgia and myoglobinuria. Amyloid deposition in the muscle biopsy is helpful
      for the diagnosis. A novel homozygous ANO5 deletion was identified, suggesting
      that screening for common mutations may have low yield in non-European subjects.

PMID- 24889863
TI  - The reasons for betel-quid chewing scale: assessment of factor structure,
      reliability, and validity.
AB  - BACKGROUND: Despite the fact that betel-quid is one of the most commonly used
      psychoactive substances worldwide and a major risk-factor for head-and-neck
      cancer incidence and mortality globally, currently no standardized instrument is
      available to assess the reasons why individuals chew betel-quid. A measure to
      assess reasons for chewing betel-quid could help researchers and clinicians
      develop prevention and treatment strategies. In the current study, we sought to
      develop and evaluate a self-report instrument for assessing the reasons for
      chewing betel quid which contributes toward the goal of developing effective
      interventions to reduce betel quid chewing in vulnerable populations. METHODS:
      The current study assessed the factor structure, reliability and convergent
      validity of the Reasons for Betel-quid Chewing Scale (RBCS), a newly developed 10
      item measure adapted from several existing "reasons for smoking" scales. The
      measure was administered to 351 adult betel-quid chewers in Guam. RESULTS:
      Confirmatory factor analysis of this measure revealed a three factor structure:
      reinforcement, social/cultural, and stimulation. Further tests revealed strong
      support for the internal consistency and convergent validity of this three factor
      measure. CONCLUSION: The goal of designing an intervention to reduce betel-quid
      chewing necessitates an understanding of why chewers chew; the current study
      makes considerable contributions towards that objective.

PMID- 24889864
TI  - Comparative analysis of chemical and microbial profiles in estuarine sediments
      sampled from Kanto and Tohoku regions in Japan.
AB  - Estuarine environments accumulate large quantities of organic matter from land
      masses adjoining the sea, and this is consumed as part of the detritus cycle.
      These environments are rich in biodiversity, and their ecosystem services greatly
      benefit humans. However, the estuarine environments have complicated aqueous
      ecosystems, thus the comprehensive evaluation of biotic interactions and
      stability is difficult using conventional hypothesis-driven approaches. In this
      study, we describe the advancement of an evaluation strategy for characterizing
      and visualizing the interactions and relationships among the microorganisms and
      chemicals in sediment ecosystems of estuarine environments by a combination of
      organic matter and elemental profiling as well as microbial profiling. We also
      report our findings from a comparative analysis of estuarine and coastal
      environmental samples collected from the Kanto and Tsunami-affected Tohoku
      regions in Japan. The microbial-gated correlation deployed from the coefficient
      of microbiota from the correlation matrix and network analysis was able to
      visualize and summarize the different relationships among the microbial
      communities, sediment organic matter, and element profiles based on geographical
      differences in Kanto and Tohoku regions. We demonstrated remarkable estuarine
      eutrophication in the Kanto region based on abundant sediment polypeptide signals
      and water nitrogen ions catabolized by microbiota. Therefore, we propose that
      this data-driven approach is a powerful method for analyzing, visualizing, and
      evaluating complex metabolic dynamics and networks in sediment microbial
      ecosystems and can be applied to other environmental ecosystems, such as deep sea
      sediments and agronomic and forest soils. 

PMID- 24889865
TI  - Pelvic and reproductive structures in placoderms (stem gnathostomes).
AB  - Newly discovered pelvic and reproductive structures within placoderms,
      representing some of the most crownward members of the gnathostome stem group and
      the most basal jawed vertebrates, challenge established ideas on the origin of
      the pelvic girdle and reproductive complexity. Here we critically review previous
      descriptions of the pelvic structures in placoderms and reinterpret the
      morphology of the pelvic region within the arthrodires and ptyctodonts, in
      particular the position of the pelvic fin and the relationship of the male
      clasper to the pelvic girdle. Absence of clear articular surfaces on the clasper
      and girdle in the Arthrodira, along with evidence from the Ptyctodontida, suggest
      that these are separate structures along the body. We describe similarities
      between the pectoral and pelvic girdles and claspers, for example, all these have
      both dermal and perichondral (cartilaginous) components. Claspers in placoderms
      and chondrichthyans develop in very different ways; in sharks, claspers develop
      from the pelvic fin while the claspers in placoderms develop separately,
      suggesting that their independent development involved a posterior extension of
      the 'competent stripes' for fin development previously limited to the region
      between the paired pectoral and pelvic fins. Within this expanded zone, we
      suggest that clasper position relative to the pelvic fins was determined by genes
      responsible for limb position. Information on early gnathostome reproductive
      processes is preserved in both the Ptyctodontida and Arthrodira, including the
      presence of multiple embryos in pregnant females, embryos of differing sizes and
      of different sexes (e.g. male claspers preserved in some embyros). By comparison
      with chondrichthyans, these observations suggest more complex reproductive
      strategies in placoderms than previously appreciated. 

PMID- 24889867
TI  - Enzyme kinetics studies on 29-kDa human liver cathepsin L.
AB  - Enzyme kinetics studies reported in the literature showed that human liver
      Cathepsin L is active only at lysosomal acidic pH values, while biochemical
      studies in living cells showed that the enzyme works even at neutral pH values
      (in a condition compatible with the extracellular compartment). Such an apparent
      ambiguity highlighted the need of analysing in depth the kinetics of ~29-kDa
      Cathepsin L, which is the form commonly used in experiments. The stability and
      catalytic activity of this enzyme were investigated at different pH values,
      reducing and non-reducing environments, presence of copper, iron and zinc ions,
      and presence of the natural modulator/inhibitor cystatin B. Our experiments
      showed that ~29-kDa human liver Cathepsin L is stable and catalytically
      functional even at neutral pH values and under non-reducing conditions, which
      simulate the extracellular compartment. Under these conditions, Cathepsin L was
      also proved to interact with cystatin B, being also modulated by physiological
      concentrations of Cu(++) , Fe(++) and Zn(++) . This paper suppose an advance in
      the comprehension of the catalytic properties of human liver Cathepsin L, its
      implications in different physiological processes and its potential use within a
      drug screening programme in which agents acting extracellularly are being
      considered. 

PMID- 24889866
TI  - Imaging genomic mapping of an invasive MRI phenotype predicts patient outcome and
      metabolic dysfunction: a TCGA glioma phenotype research group project.
AB  - BACKGROUND: Invasion of tumor cells into adjacent brain parenchyma is a major
      cause of treatment failure in glioblastoma. Furthermore, invasive tumors are
      shown to have a different genomic composition and metabolic abnormalities that
      allow for a more aggressive GBM phenotype and resistance to therapy. We thus seek
      to identify those genomic abnormalities associated with a highly aggressive and
      invasive GBM imaging-phenotype. METHODS: We retrospectively identified 104
      treatment-naive glioblastoma patients from The Cancer Genome Atlas (TCGA) whom
      had gene expression profiles and corresponding MR imaging available in The Cancer
      Imaging Archive (TCIA). The standardized VASARI feature-set criteria were used
      for the qualitative visual assessments of invasion. Patients were assigned to
      classes based on the presence (Class A) or absence (Class B) of statistically
      significant invasion parameters to create an invasive imaging signature; imaging
      genomic analysis was subsequently performed using GenePattern Comparative Marker
      Selection module (Broad Institute). RESULTS: Our results show that patients with
      a combination of deep white matter tracts and ependymal invasion (Class A) on
      imaging had a significant decrease in overall survival as compared to patients
      with absence of such invasive imaging features (Class B) (8.7 versus 18.6 months,
      p < 0.001). Mitochondrial dysfunction was the top canonical pathway associated
      with Class A gene expression signature. The MYC oncogene was predicted to be the
      top activation regulator in Class A. CONCLUSION: We demonstrate that MRI
      biomarker signatures can identify distinct GBM phenotypes associated with highly
      significant survival differences and specific molecular pathways. This study
      identifies mitochondrial dysfunction as the top canonical pathway in a very
      aggressive GBM phenotype. Thus, imaging-genomic analyses may prove invaluable in
      detecting novel targetable genomic pathways.

PMID- 24889868
TI  - Pioglitazone does not affect the risk of kidney cancer in patients with type 2
      diabetes.
AB  - OBJECTIVE: To investigate whether pioglitazone treatment of patients with type 2
      diabetes mellitus was associated with an increased risk of kidney cancer.
      METHODS: The reimbursement databases of all Taiwanese patients with type 2
      diabetes who received oral anti-diabetic agents or insulin from 1996 to 2009 were
      retrieved from the National Health Insurance. An entry date was set at 1 January
      2006, and a total of 1,093,675 patients with type 2 diabetes were followed up for
      kidney cancer incidence until the end of 2009. The incidences of kidney cancer
      among patients who had and had not received pioglitazone, as well as among
      subgroups of those treated with pioglitazone (sorted by time since starting
      pioglitazone, duration of treatment and cumulative dose) were calculated and
      hazard ratios (HRs) estimated by Cox regression analysis. RESULTS: Of the
      1,093,675 patients, 58,172 (5.3%) had and 1,035,503 (94.7%) had not received
      pioglitazone, with incident kidney cancer developing in 208 (0.36%) and 3304
      (0.32%) patients, respectively, and a respective incidence of 97.7 and 90.5 per
      100,000 person-years. Pioglitazone and kidney cancer were not significantly
      associated in unadjusted (HR 1.04; 95% confidence interval (CI), 0.90-1.20), age
      sex-adjusted (HR 1.09; 95% CI, 0.95-1.25), and fully adjusted (HR 1.09; 95% CI,
      0.94-1.26) models. None of the dose-response parameters showed a significant
      trend of risk association, with all P-trends >0.10. CONCLUSIONS: Pioglitazone
      does not affect the risk of kidney cancer.

PMID- 24889869
TI  - Modulation of primary cell function of host Pseudomonas bacteria by the
      conjugative plasmid pCAR1.
AB  - The impacts of plasmid carriage on the host cell were comprehensively analysed
      using the conjugative plasmid pCAR1 in three different Pseudomonas hosts, P.
      putida KT2440, P. aeruginosa PAO1 and P. fluorescens Pf0-1. Plasmid carriage
      reduced host fitness, swimming motility, and resistance to osmotic or pH stress.
      Plasmid carriage brought about alterations in primary metabolic capacities in the
      TCA cycle of the hosts. Differentially transcribed genes in the three hosts
      associated with plasmid carriage were identified by growth phase-dependent
      transcriptome analyses. Plasmid carriage commonly showed a greater effect on the
      host transcriptome at the transition and early stationary phases. The
      transcriptome alterations were similar between KT2440 and PAO1. Transcriptions of
      numbers of genes encoding ribosomal proteins, F-type ATPase, and RNAP core in
      both strains were not suppressed enough in the early stationary phase by plasmid
      carriage. These responses may have been responsible for the reduction in host
      fitness, motility and stress resistances. Host-specific responses to plasmid
      carriage were transcriptional changes of genes on putative prophage or foreign
      DNA regions. The extents of the impacts on host phenotypes and transcriptomes
      were similarly greatest in KT2440 and lowest in Pf0-1. These findings suggest
      that host cell function was actively regulated by plasmid carriage. 

PMID- 24889870
TI  - Urokinase-type plasminogen activator receptor (uPAR) on tumor-associated
      macrophages is a marker of poor prognosis in colorectal cancer.
AB  - Patients were identified from a population-based prospective study of 4990
      individuals with symptoms associated with colorectal cancer (CRC). A total of 244
      CRC tissue samples were available for immunohistochemical staining of uPAR,
      semiquantitatively scored at the invasive front, and in the tumor core on cancer
      cells, macrophages, and myofibroblasts. In addition, the levels of the intact and
      cleaved uPAR-forms in blood from the same patients are evaluated in this study.
      In a univariate analysis, the number of uPAR-positive versus uPAR-negative
      macrophages (HR = 2.26, [95% CI: 1.39-3.66, P = 0.0009]) and cancer cells
      (HR=1.49, [95% CI: 1.01-2.20, P = 0.047]) located in the tumor core were
      significantly associated to overall survival. In a multivariate analysis, uPAR
      positive versus uPAR-negative macrophages located in the tumor core showed the
      best separation of patients with positive score associated to poor prognosis (HR
      = 1.84 [95% CI: 1.12-3.04, P = 0.017]). In a multivariate analysis including
      clinical covariates and soluble uPAR(I), the latter was significantly associated
      to overall survival (HR = 2.68 [95% CI: 1.90-3.79, P < 0.0001]) and uPAR-positive
      macrophages in the tumor core remained significantly associated to overall
      survival (HR = 1.81 [95% CI: 1.08-3.01, P = 0.023]). Membrane-bound uPAR showed
      additive effects with the circulating uPAR(I) and stage, giving a hazard ratio of
      12 between low and high scores. Thus, combining stage, uPAR(I) in blood and uPAR
      on macrophages in the tumor core increase the prognostic precision more than
      tenfold, as compared to stage alone.

PMID- 24889871
TI  - Affinity of zinc and copper ions for insulin monomers.
AB  - Zinc is an essential trace element involved in the correct packing and storage of
      insulin. Total zinc content in the pancreatic beta-cells is among the highest in
      the body and changes in the Zn(2+) levels have been found to be associated with
      diabetes. The most common form of the Zn-insulin complex is a hexamer containing
      two zinc ions. However, zinc can also form other complexes with insulin, whereas
      dissociation constants of these complexes are not known. We have determined that
      the dissociation constant value of the monomeric 1 : 1 Zn-insulin complex is
      equal to 0.40 MUM. The apparent binding affinity decreases drastically at higher
      insulin concentrations where the peptide forms dimers. Cu(2+) ions also bind to
      monomeric insulin, whereas the apparent Cu(2+)-binding affinity depends on HEPES
      concentration. The conditional dissociation constant of the Cu(2+)-insulin
      complex is equal to 0.025 MUM. The analysis demonstrates that insulin cannot form
      complexes with zinc ions in circulation due to the low concentration of free
      Zn(2+) in this environment. 

PMID- 24889872
TI  - In memoriam: Ronald D. Mann, MD, FRCP, FRCGP, FFPM, FISPE, Professor Emeritus,
      Honorary Lifetime ISPE Fellow, 1928-2013: perspective from Medicines Regulators.

PMID- 24889873
TI  - In memoriam: Ronald D. Mann, MD, FRCP, FRCGP, FFPM, FISPE, Professor Emeritus,
      Honorary Lifetime ISPE Fellow, 1928-2013: perspective from the Journal.

PMID- 24889874
TI  - In memoriam: Ronald D. Mann, MD, FRCP, FRCGP, FFPM, FISPE, Professor Emeritus,
      Honorary Lifetime ISPE Fellow, 1928-2013: Perspectives of ISPE's Founding
      Executuve Director.

PMID- 24889875
TI  - Configuration and conformation of alfentanil hydrochloride. Conformational study
      by NMR and theoretical calculations.
AB  - The configurational and conformational structure of alfentanil hydrochloride (1)
      was studied by nuclear magnetic resonance and theoretical calculations. Compound
      1 is best described by equilibrium between two stereoisomeric piperidinium rings
      with the N-substituent always being in equatorial position. Nuclear magnetic
      resonance spectra demonstrate that, depending on the solvent, 1 adopts the
      conformation with an axial methoxymethylene group. Computations were crucial in
      determining the importance of the transannular attractive interaction between the
      positive charge at the piperidinium N-atom and the methoxymethyl group in
      position 4.

PMID- 24889876
TI  - High takeoff of the right coronary artery associated with ventricular septal
      defect, right aortic arch, and bridging bronchus.
AB  - We report a case of a 14-year-old female with abnormally high takeoff of the
      right coronary artery (RCA) that was associated with a ventricular septal defect,
      right aortic arch, and bridging bronchus. During surgery, an exceptionally high
      takeoff of the RCA was discovered. Postoperative computed tomography confirmed
      the presence of the associated right aortic arch with anomalous branching
      pattern, and bridging bronchus.

PMID- 24889877
TI  - Taking ICPD beyond 2015: negotiating sexual and reproductive rights in the next
      development agenda.
AB  - On the twentieth anniversary of the International Conference on Population and
      Development (ICPD), activists, governments and diplomats engaged in the fight for
      sexual and reproductive health and rights (SRHR) are anxious to ensure that these
      issues are fully reflected in the development agenda to succeed the Millennium
      Development Goals after 2015. In inter-governmental negotiations since 1994 and
      particularly in the period 2012-2014, governments have shown that they have
      significantly expanded their understanding of a number of so-called
      'controversial' issues in the ICPD agenda, whether safe abortion, adolescent
      sexual and reproductive health services, comprehensive sexuality education or
      sexual rights. As in the past and in spite of an increasingly complex and
      difficult multilateral environment, countering the highly organised conservative
      opposition to SRHR has required a well-planned and determined mobilisation by
      progressive forces from North and South. 

PMID- 24889879
TI  - Electrophilic trifluoromethylthiolation of carbonyl compounds.
AB  - A general method for the alpha-trifluoromethylthiolation of carbonyl compounds,
      without prefunctionalization, has been developed. Aldehydes, ketones, esters,
      amides, keto-esters, alkaloids, and steroids have been trifluoromethylthiolated
      with good yields. This work, proposing a new reagent for electrophilic
      trifluoromethylthiolation, provides a route towards the original synthesis of
      various trifluoromethylthiolated molecules for further applications. 

PMID- 24889878
TI  - Protocol in managing oral surgical patients taking dabigatran.
AB  - New anticoagulants are being introduced into the market. These drugs are orally
      administered, have predictable pharmacokinetics and dose response, do not require
      monitoring and have an acceptable safety profile when used appropriately, and so
      avoid many of the disadvantages and possible complications of warfarin and
      heparin. Dabigatran is the most widely used, and has been approved by the
      Therapeutic Goods Administration. The use of dabigatran will likely increase in
      the coming years, and so it is important for dentists to be aware of its
      mechanism of action, the possible complications, and how to reverse the bleeding
      if it occurs. This review discusses dabigatran and reports on our experience of
      five cases, and provides practical clinical advice on how to manage patients on
      dabigatran who require dental treatment, particularly extractions. 

PMID- 24889880
TI  - Inter-arm blood pressure difference in hospitalized elderly patients--is it
      consistent?
AB  - Inter-arm blood pressure difference (IAD) is recognized as a risk factor for
      cardiovascular mortality. Its reproducibility in the elderly is unknown. The
      authors determined the prevalence and reproducibility of IAD in hospitalized
      elderly patients. Blood pressure was measured simultaneously in both arms on two
      different days in elderly individuals hospitalized in a geriatric ward. The study
      included 364 elderly patients (mean age, 85+/-5 years). Eighty-four patients
      (23%) had systolic IAD >10 and 62 patients (17%) had diastolic IAD >10 mm Hg. A
      total of 319 patients had two blood pressure measurements. Systolic and diastolic
      IAD remained in the same category in 203 (64%) and 231 (72%) patients,
      respectively. Correlations of systolic and diastolic IAD between the two
      measurements were poor. Consistency was not affected by age, body mass index,
      comorbidities, or treatment. IAD is extremely common in hospitalized elderly
      patients, but, because of poor consistency, its clinical significance in this
      population is uncertain. 

PMID- 24889881
TI  - Action attenuates the effect of visibility on gesture rates.
AB  - Much evidence suggests that semantic characteristics of a message (e.g., the
      extent to which the message evokes thoughts of spatial or motor properties) and
      social characteristics of a speaking situation (e.g., whether there is a listener
      who can see the speaker) both influence how much speakers gesture. However, the
      Gesture as Simulated Action (GSA) framework (Hostetter & Alibali, ) predicts that
      these effects should not be independent but should interact such that the effect
      of visibility is lessened when a message evokes strong thoughts of action. This
      study tested this claim by comparing the gesture rates produced by speakers as
      they described 24 nouns that vary in how strongly they evoke thoughts of action.
      Further, half of the words were described with visibility between speaker and
      listener blocked. The results demonstrated a significant interaction as predicted
      by the GSA framework.

PMID- 24889883
TI  - Heterogeneity and plasticity in the development of language: a 17-year follow-up
      of children referred early for possible autism.
AB  - BACKGROUND: Delayed, abnormal language is a common feature of autism and language
      therapy often a significant component of recommended treatment. However, as with
      other disorders with a language component, we know surprisingly little about the
      language trajectories and how varied these might be across different children.
      Thus, we know little about how and when language problems might resolve, whether
      there are periods of relative stability or lack of change and what periods might
      offer more favourable circumstances for intervention. METHODS: Expressive and
      receptive language was measured on six occasions between age 2 and 19 on a cohort
      of 192 children initially referred for autism. Latent class growth models were
      fitted to characterize the patterns of heterogeneous development. RESULTS: Latent
      class growth analysis identified seven classes. Between age 6 and 19, all classes
      tracked in parallel. Between ages 2 and 6, development was more heterogeneous
      with considerable variation in relative progress. In all groups, receptive and
      expressive language developed very largely in tandem. CONCLUSIONS: The results
      confirmed previous analysis of children with specific language impairment where
      progress beyond age 6 was remarkably uniform. Greater variation was evident
      before this age with some groups making clearly better or worse progress compared
      to others. While this developmental heterogeneity may simply be a reflection of
      variation in preexisting and unchanging biological disposition, it may also
      reflect, at least in part, greater sensitivity in the early years to environments
      that are more or less supportive of language development. These findings
      contribute to the case for the importance of early intervention.

PMID- 24889882
TI  - Suppression of blastogenesis and proliferation of activated CD4(+) T cells:
      intravenous immunoglobulin (IVIg) versus novel anti-human leucocyte antigen (HLA)
      E monoclonal antibodies mimicking HLA-I reactivity of IVIg.
AB  - Activated CD4(+) T cells undergo blastogenesis and proliferation and they express
      several surface receptors, including beta2-microglobulin-free human leucocyte
      antigen (HLA) heavy chains (open conformers). Intravenous immunoglobulin (IVIg)
      suppresses activated T cells, but the mechanism is unclear. IVIg reacts with HLA
      Ia/Ib antigens but its reactivity is lost when the anti-HLA-E Ab is adsorbed out.
      Anti-HLA-E antibodies may bind to the peptides shared by HLA-E and the HLA-I
      alleles. These shared peptides are cryptic in intact HLA, but exposed in open
      conformers. The hypothesis that anti-HLA-E monoclonal antibodies (mAbs) that
      mimic HLA-I reactivity of IVIg may suppress activated T cells by binding to the
      shared peptides of the open conformers on the T cell surface was tested by
      examining the relative binding affinity of those mAbs for open conformers coated
      on regular beads and for intact HLA coated on iBeads, and by comparing the
      effects on the suppression of phytohaemagglutinin (PHA)-activated T cells of
      three entities: IVIg, anti-HLA-E mAbs that mimic IVIg [Terasaki Foundation
      Laboratory (TFL)-006 and (TFL)-007]; and anti-HLA-E antibodies that do not mimic
      IVIg (TFL-033 and TFL-037). Suppression of blastogenesis and proliferation of
      those T cells by both IVIg and the anti-HLA-E mAbs was dose-dependent, the dose
      required with mAbs 50-150-fold lower than with IVIg. TFL-006 and TFL-007
      significantly suppressed blastogenesis and proliferation of activated CD4(+) T
      cells, but neither the non-IVIg-mimicking mAbs nor control antibodies did so. The
      suppression may be mediated by Fab-binding of TFL-006/TFL-007 to the exposed
      shared peptides. The mAb binding to the open conformer may signal T cell
      deactivation because the open conformers have an elongated cytoplasmic tail with
      phosphorylation sites (tryosine(320)/serine(335)).

PMID- 24889884
TI  - Extracorporeal shockwaves (ESWs) enhance the osteogenic medium-induced
      differentiation of adipose-derived stem cells into osteoblast-like cells.
AB  - Human adipose-derived stem cells (hASCs) are a promising cell type for bone
      tissue engineering, given their potential to differentiate into osteoblast-like
      cells. Interactions among biochemical and mechanical signals result in bone
      formation and repair. In this process stem cells have a crucial role.
      Extracorporeal shockwaves (ESWs) are acoustic waves capable of enhancing bone
      regeneration, suggesting that ESWs may induce some signals for mesenchymal
      progenitor maturation. The aim of the present work is to investigate the effects
      of ESW treatment on the differentiation of hASCs into osteoblast-like cells and
      to better clarify the mechanisms involved. The hASCs were treated with ESWs and
      osteogenic medium, and the effects in terms of gene expression, alkaline
      phosphatase (ALP) activity and calcium deposition were then evaluated. Moreover,
      to investigate the mechanisms of ESW action, reactive oxygen species (ROS)
      production, extracellular-signal-regulated kinase (ERK) and small 'mothers
      against' decapentaplegic (Smad) phosphorylation, and bone morphogenetic protein 2
      (BMP2) expression were assessed. The ESW treatment increased Runt-related
      transcription factor 2 (Runx2), ALP and BMP2 expression, as well as ALP activity
      and calcium deposits with respect to untreated cells. Moreover ESWs induced ROS
      formation, and both ERK and Smad phosphorylation. The present study shows the
      effects of ESWs on osteogenic differentiation in an in vitro model using hASCs
      and defines the mechanisms involved in this process. The observations suggest
      that the combination of autologous hASCs and ESW treatment may improve bone
      tissue repair in tissue engineering procedures. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 24889885
TI  - Self-directed community services for older Australians: a stepped capacity
      building approach.
AB  - Consumer-directed care (CDC) is increasingly widespread among aged care service
      options in Organisation for Economic Co-operation and Development (OECD)
      countries. However, the evidence base regarding the programmatic and contextual
      factors that affect the outcome of CDC interventions is surprisingly small. This
      paper reports on a self-directed care approach for older Australians with complex
      care needs. A multi-methods longitudinal comparative cohort study was employed
      comprising 4 survey tools and 56 semi-structured interviews. Participation rates
      were around 20%. A total of 185 (98 in the intervention and 87 in the control
      group) older people and carers were recruited at baseline. Eleven months later,
      109 participants (59 in the intervention and 50 in the control group) completed
      the repeat measure. Attrition rates were around 40%. Data collection occurred
      between July 2010 and April 2012. The data suggest that intervention group
      participants were likely to be more satisfied with the way they were treated (P =
      0.013), their care options (P = 0.014), the 'say' they had in their care (P <
      0.001), the information they received regarding their care (P = 0.012), what they
      were achieving in life (P = 0.031), that the services changed their view on what
      could be achieved in life (P = 0.020) and with their standard of living (P =
      0.008). The evaluation suggests that while only a very small segment of older
      people is interested in a voucher or cash option, a substantially larger group
      would like to have greater say over and more direct access to their care,
      without, however, assuming administrative and financial responsibilities. The
      paper concludes that a stepped capacity-building approach to CDC may improve the
      acceptability of CDC to older people and generate synergies that improve older
      people's care outcomes. 

PMID- 24889887
TI  - Detection of Different Bovine Papillomavirus Types and Co-infection in
      Bloodstream of Cattle.
AB  - Bovine papillomavirus (BPV) is a diverse group of double-stranded DNA oncogenic
      viruses. BPVs are classically described as epitheliotropic, however, they have
      been detected in body fluids, such as blood and semen. The presence of BPV in
      these sites can have implications for the dissemination of BPV. The aim of this
      study was to verify the prevalence of BPV types in cattle blood. A total of 57
      blood samples were analyzed by PCR using BPV type-specific primers to BPVs 1-6
      and 8-10, and subsequent sequencing. Sequencing quality was determined using
      Staden package with Phred 20. Similarity analysis was performed with BioEdit and
      BLAST programs to assess the identity with known BPV types. Statistical analysis
      was performed by Fisher's exact test. The results showed seven different types of
      BPVs in the blood, with the exception of BPV 5 and 9. This is the first study
      that demonstrates BPVs 3, 6, 8 and 10 DNA in cattle blood. BPVs 1 and 2 were the
      viral types most frequent in blood, while BPVs 4 and 10 were the least frequent
      types. All the samples showed co-infection by at least two BPV types. These data
      suggest that several BPV types may infect blood cells at the same time and
      demonstrate the possibility that the BPV infection in non-epithelial tissue can
      occur without restriction to one or two viral types. These results can contribute
      to future studies aimed at the control and prevention of papillomaviruses. 

PMID- 24889888
TI  - Latent heat exchange in the boreal and arctic biomes.
AB  - In this study latent heat flux (lambdaE) measurements made at 65 boreal and
      arctic eddy-covariance (EC) sites were analyses by using the Penman-Monteith
      equation. Sites were stratified into nine different ecosystem types: harvested
      and burnt forest areas, pine forests, spruce or fir forests, Douglas-fir forests,
      broadleaf deciduous forests, larch forests, wetlands, tundra and natural
      grasslands. The Penman-Monteith equation was calibrated with variable surface
      resistances against half-hourly eddy-covariance data and clear differences
      between ecosystem types were observed. Based on the modeled behavior of surface
      and aerodynamic resistances, surface resistance tightly control lambdaE in most
      mature forests, while it had less importance in ecosystems having shorter
      vegetation like young or recently harvested forests, grasslands, wetlands and
      tundra. The parameters of the Penman-Monteith equation were clearly different for
      winter and summer conditions, indicating that phenological effects on surface
      resistance are important. We also compared the simulated lambdaE of different
      ecosystem types under meteorological conditions at one site. Values of lambdaE
      varied between 15% and 38% of the net radiation in the simulations with mean
      ecosystem parameters. In general, the simulations suggest that lambdaE is higher
      from forested ecosystems than from grasslands, wetlands or tundra-type
      ecosystems. Forests showed usually a tighter stomatal control of lambdaE as
      indicated by a pronounced sensitivity of surface resistance to atmospheric vapor
      pressure deficit. Nevertheless, the surface resistance of forests was lower than
      for open vegetation types including wetlands. Tundra and wetlands had higher
      surface resistances, which were less sensitive to vapor pressure deficits. The
      results indicate that the variation in surface resistance within and between
      different vegetation types might play a significant role in energy exchange
      between terrestrial ecosystems and atmosphere. These results suggest the need to
      take into account vegetation type and phenology in energy exchange modeling. 

PMID- 24889889
TI  - Oral administration of Lactobacillus paracasei alleviates clinical symptoms of
      colitis induced by dextran sulphate sodium salt in BALB/c mice.
AB  - The aim of this study was to investigate the alleviating effect of Lactobacillus
      paracasei subsp. paracasei LC-01 (LC-01) on the murine model of colitis induced
      by dextran sulphate sodium (DSS). 50 pathogen-free, 6-week-old male BALB/c mice
      were divided randomly into 5 groups, including a control group and four DSS-LC-01
      treated groups (DSS, DSS-106, DSS-108, and DSS-1010 with 0, 1*106, 1*108 and
      1*1010 cfu/ml LC-01, respectively). To test the effectiveness of LC-01 as a
      prophylactic it was administered for 7 days before the onset of the disease in
      DSS-LC-01-treated mice. After 7 days, colitis was induced by administration of
      2.5% (w/v) DSS in drinking water for a further 7 days. The disease activity index
      (DAI), histological score, myeloperoxidase (MPO) activity and the level of the
      pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis
      factor alpha (TNF-alpha) were measured. DAI, histological scores and MPO activity
      of mice treated with a medium or high dose of LC-01 were significantly lower
      compared to a low-dose of LC-01 and DSS treatment alone (P<0.05). Colon length
      shortening could be prevented with increasing dose of LC-01. In addition, the
      levels of IL-1beta and TNF-alpha were suppressed significantly by treatment with
      a medium and high dose of LC-01. However, no significant difference in the
      indices mentioned above were observed between a low dose of LC-01 and treatment
      with DSS alone (P?0.05). An appropriate dose of LC-01 can prevent intestinal
      damage in mice with DSS-induced colitis. The expression of inflammatory cytokines
      related to pathogenesis of DSS-induced colitis decreased following treatment with
      LC-01.

PMID- 24889886
TI  - Neuroinflammation and M2 microglia: the good, the bad, and the inflamed.
AB  - The concept of multiple macrophage activation states is not new. However,
      extending this idea to resident tissue macrophages, like microglia, has gained
      increased interest in recent years. Unfortunately, the research on peripheral
      macrophage polarization does not necessarily translate accurately to their
      central nervous system (CNS) counterparts. Even though pro- and anti-inflammatory
      cytokines can polarize microglia to distinct activation states, the specific
      functions of these states is still an area of intense debate. This review
      examines the multiple possible activation states microglia can be polarized to.
      This is followed by a detailed description of microglial polarization and the
      functional relevance of this process in both acute and chronic CNS disease models
      described in the literature. Particular attention is given to utilizing M2
      microglial polarization as a potential therapeutic option in treating diseases. 

PMID- 24889891
TI  - Understanding gut microbiota in elderly's health will enable intervention through
      probiotics.
AB  - Today, advances in the public health system of most countries have managed to
      extend notably life expectancy, however, elderly's health remain as a very
      serious concern. The lifelong stimulation of innate and adaptive immune systems
      leads to immunosenescence and, as result, to a low ability to produce
      immunoglobulins against pathogens but also to a low-grade chronic inflammatory
      state (inflammaging) that is linked to most age-related health problems, such as
      dementia, Alzheimer or atherosclerosis. This inflammatory state could make the
      host more sensitive to intestinal microbes, or vice versa, as changes in the gut
      microbiota composition are related to the progression of diseases and frailty in
      the elderly population. It was considered that gut microbiota changed during
      aging, with an increase of Bacteroidetes vs. Firmicutes proportion and a
      reduction of bifidobacterial counts, however recent studies reported a great
      inter-individual variation among elderly and a significant relationship between
      gut microbiota, diet and institution or community living. Intervention studies of
      probiotics and prebiotics in elderly are not very abundant, but most cases showed
      that Bifidobacterium populations can efficiently be stimulated with a concomitant
      decrease of Enterobacteria. Furthermore, also some studies demonstrated that
      probiotics decreased the synthesis of pro-inflammatory cytokines which are
      upregulated in the elderly, such as interleukin (IL)-8, IL-6 or tumour necrosis
      factor ?, among others, and they increased the levels of activated lymphocytes,
      natural killer cells, phagocytic activity and even showed a greater response to
      influenza vaccination. This suggests that direct manipulation of the gut
      microbiota may improve adaptive immune response and reduce inflammatory
      secretions, therefore compensating immunosenescence effects, however, there are
      no records of their effect on clinical symptoms or risk for disease. Those facts
      reveal that this is an open research field with very good scientific perspectives
      and above all they could bring likely improvements in the wellbeing of our
      seniors.

PMID- 24889892
TI  - Bifidobacteria from the gastrointestinal tract of animals: differences and
      similarities.
AB  - At present, the genus Bifidobacterium includes 48 species and subspecies, and
      this number is expected to increase. Bifidobacteria are found in different
      ecological niches. However, most were originally isolated from animals, mainly
      mammals, especially during the milk feeding period of life. Their presence in
      high numbers is associated with good health of the host. Moreover, bifidobacteria
      are often found in poultry and insects that exhibit a social mode of life
      (honeybees and bumblebees). This review is designed as a summary of currently
      known species of the genus Bifidobacterium, especially focused on their
      difference and similarities. The primary focus is on their occurrence in the
      digestive tract of animals, as well as the specificities of animal strains, with
      regard to their potential use as probiotics. 

PMID- 24889893
TI  - Effect of tablets containing probiotic bacteria (Lactobacillus reuteri) on early
      caries lesions in adolescents: a pilot study.
AB  - The objective of the study was to investigate the effect of tablets containing
      probiotic lactobacilli on early caries lesions in adolescents with quantitative
      light-induced fluorescence (QLF). 36 healthy adolescents of both sexes (12-17
      years of age) were enrolled and randomly allocated to a placebo-controlled trial
      with two parallel groups. The test group received two tablets daily containing
      two strains of Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) for a period
      of three months, while the control group got identical placebo tablets without
      live bacteria. The primary outcome was QLF-readings (change in fluorescence,
      DeltaF and lesion area, mm2) at baseline and after 3 months, conducted at two
      buccal sites of each individual, pre-selected with clearly visible clinical signs
      of enamel demineralisation (white spots). Significantly more premolars were
      allocated to the placebo group, while the test group had more incisors (P<0.05).
      There were no statistically significant differences in fluorescence values
      between the groups, neither at baseline, nor at the follow-up. There was however
      a significant decrease in fluorescence over time in the test group, but not in
      the placebo group (P<0.05). No alterations of the lesion area (DeltaA) were found
      in any group. The inter-examiner intra-class correlation coefficient-value for
      QLF-readings was excellent. No side- or adverse effects were reported during the
      intervention period. This pilot study found a significant decrease over time in
      the test group. However, no statistically significant differences in fluorescence
      values between the groups were found. Hence, the null hypothesis could not be
      rejected. 

PMID- 24889894
TI  - Characterisation and preliminary lipid-lowering evaluation of Lactobacillus
      isolated from a traditional Serbian dairy product.
AB  - We investigated the potential probiotic properties of indigenous lactic acid
      bacteria (LAB) isolated from Serbian homemade cheese. Seventeen LAB strains were
      isolated and characterised using standard protocols. One of the strains showed
      several probiotic properties: survival at low pH and in bile salts solution,
      antimicrobial activity, susceptibility to antibiotics and adhesion to hexodecane.
      DNA analysis identified the isolate as Lactobacillus casei, hereafter named L.
      casei 5s. The lipid lowering effect of L. casei 5s was evaluated in vivo using a
      hyperlipidemic rat model. Orally administered L. casei 5s significantly decreased
      the elevated total serum cholesterol and triglycerides, and attenuated macro
      vesicular steatosis in the liver. Moreover, L. casei 5s improved the intestinal
      microbial balance in favour of lactobacilli, while decreasing the number of
      Escherichia coli cells. The bacteria were re-isolated and identified from the
      surface of the intestinal mucosa and from the faecal samples of treated animals,
      indicating adhesiveness and colonisation ability. The results of an acute oral
      toxicity study in mice and the absence of translocation to other organs
      demonstrated the safety of the strain. In conclusion, L. casei 5s demonstrated
      promising probiotic potential and might be a good candidate for more detailed
      investigations. 

PMID- 24889895
TI  - Deciphering meta-analytic results: a mini-review of probiotics for the prevention
      of paediatric antibiotic-associated diarrhoea and Clostridium difficile
      infections.
AB  - Meta-analyses are used to evaluate pooled effects of a wide variety of
      investigational agents, but the interpretation of the results into clinical
      practices may be difficult. This mini-review offers a three-step process to
      enable healthcare providers to decipher pooled meta-analysis estimates into
      results that are useful for therapeutic decisions. As an example of how meta
      analyses should be interpreted, a recent meta-analysis of probiotics for the
      prevention of paediatric antibiotic-associated diarrhoea (AAD) and the prevention
      of Clostridium difficile infections (CDI) will be used. First, the pooled results
      of this meta-analysis indicates a significant protective efficacy for AAD is
      found when the 16 different types of probiotics are combined (pooled relative
      risk (RR) = 0.43, 95% confidence interval (CI)=0.33-0.56) and also a significant
      reduction of paediatric CDI (pooled RR=0.34, 95%CI=0.16-0.74) was found pooling
      four different types of probiotics. Secondly, because the efficacy of probiotics
      is strain-specific, it is necessary to do a sensitivity analysis, restricting the
      meta-analysis to one specific strain. Two strains, Saccharomyces boulardii lyo
      and Lactobacillus rhamnosus GG showed significant efficacy for paediatric AAD
      when pooled (pooled RR for S. boulardii = 0.43, 95%CI=0.21-0.86 and pooled RR for
      L. rhamnosus GG = 0.44, 95%CI=0.20-0.95). Thirdly, if studies within probiotic
      types have different results, it is prudent to examine these studies individually
      to determine the reasons why non-significant differences in efficacy were found.
      By drilling down through these three analytic layers, physicians will be
      confident in recommending the correct probiotic strain to their patients. 

PMID- 24889896
TI  - In situ observation of surface species on iridium oxide nanoparticles during the
      oxygen evolution reaction.
AB  - An iridium oxide nanoparticle electrocatalyst under oxygen evolution reaction
      conditions was probed in situ by ambient-pressure X-ray photoelectron
      spectroscopy. Under OER conditions, iridium undergoes a change in oxidation state
      from Ir(IV) to Ir(V) that takes place predominantly at the surface of the
      catalyst. The chemical change in iridium is coupled to a decrease in surface
      hydroxide, providing experimental evidence which strongly suggests that the
      oxygen evolution reaction on iridium oxide occurs through an OOH-mediated
      deprotonation mechanism. 

PMID- 24889897
TI  - Antagonizing STAT3 dimerization with a rhodium(III) complex.
AB  - Kinetically inert metal complexes have arisen as promising alternatives to
      existing platinum and ruthenium chemotherapeutics. Reported herein, to our
      knowledge, is the first example of a substitutionally inert, Group 9
      organometallic compound as a direct inhibitor of signal transducer and activator
      of transcription 3 (STAT3) dimerization. From a series of cyclometalated
      rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a
      potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3
      phosphorylation and dimerization. Significantly, the complex exhibited potent
      anti-tumor activities in an in vivo mouse xenograft model of melanoma. This study
      demonstrates that rhodium complexes may be developed as effective STAT3
      inhibitors with potent anti-tumor activity. 

PMID- 24889898
TI  - Therapy: Caloric and fat intake in statin users.

PMID- 24889899
TI  - Diabetes: Measuring interarm blood pressure differences in diabetes.

PMID- 24889900
TI  - Genetics: Founder mutations identified in an inherited form of the metabolic
      syndrome.

PMID- 24889901
TI  - Obesity: Paternal obesity--a risk factor for autism?

PMID- 24889902
TI  - Review article: the management of portal hypertensive gastropathy and gastric
      antral vascular ectasia in cirrhosis.
AB  - BACKGROUND: Portal hypertensive gastropathy (PHG) and gastric antral vascular
      ectasia (GAVE) are important causes of both acute and chronic gastrointestinal
      bleeding in patients with cirrhosis. AIM: To review the current management of PHG
      and GAVE. METHODS: PubMed was searched for English language articles using the
      key words 'GAVE', 'gastric antral vascular ectasia', 'cirrhosis',
      'gastrointestinal bleeding', 'acute', 'chronic', 'portal hypertensive
      gastropathy', 'watermelon stomach', 'radiofrequency ablation', 'band ligation',
      'thermoablation' and 'TIPSS'. RESULTS: GAVE and PHG are both encountered in
      patients with cirrhosis. They can be seen in asymptomatic patients and in those
      with either acute or chronic gastrointestinal bleeding. PHG, by definition,
      requires the presence of portal hypertension, with or without cirrhosis, whereas
      GAVE requires neither cirrhosis nor portal hypertension. They can often be
      diagnosed on endoscopic appearance alone, but may require biopsy in certain
      cases. The treatment of PHG is aimed at reducing hepatic venous pressure
      gradients, most often by pharmacologic means, but may require shunt procedures in
      severe cases. Management of GAVE on the other hand is predominantly endoscopic,
      focusing on various ablative techniques. CONCLUSIONS: Gastric antral vascular
      ectasia and portal hypertensive gastropathy are distinct entities and are both
      encountered in cirrhotic patients. Management of portal hypertensive gastropathy
      is centred on reduction in portal pressures, whereas treatment of gastric antral
      vascular ectasia is predominantly endoscopic.

PMID- 24889903
TI  - Global burden of gastric cancer attributable to Helicobacter pylori.
AB  - We previously estimated that 660,000 cases of cancer in the year 2008 were
      attributable to the bacterium Helicobacter pylori (H. pylori), corresponding to
      5.2% of the 12.7 million total cancer cases that occurred worldwide. In recent
      years, evidence has accumulated that immunoblot (western blot) is more sensitive
      for detection of anti-H. pylori antibodies than ELISA, the detection method used
      in our previous analysis. The purpose of this short report is to update the
      attributable fraction (AF) estimate for H. pylori after briefly reviewing new
      evidence, and to reassess the global burden of cancer attributable to H. pylori.
      We therefore reviewed the literature for studies comparing the risk of developing
      non-cardia gastric cancer (NCGC) in cases and controls, using both ELISA and
      multiple antigen immunoblot for detection of H. pylori. The results from
      prospective studies were combined, and the new pooled estimates were applied to
      the calculation of the AF for H. pylori in NCGC, then to the burden of infection
      related cancers worldwide. Using the immunoblot-based data, the worldwide AF for
      H. pylori in NCGC increased from 74.7% to 89.0%. This implies approximately
      120,000 additional cases of NCGC attributable to H. pylori infection for a total
      of around 780,000 cases (6.2% instead of 5.2% of all cancers). These updated
      estimates reinforce the role of H. pylori as a major cause of cancer. 

PMID- 24889904
TI  - Highly effective copper-mediated gem-difluoromethylenation of arylboronic acids.
AB  - A copper-mediated gem-difluoromethylenation of aryl, heteroaryl and vinyl boronic
      acids with bromodifluoromethylated oxazole or thiazole derivatives has been
      developed. This novel reaction showed an excellent functional group tolerance and
      wide substrate scope, providing facile access to practical application in drug
      discovery and development. 

PMID- 24889905
TI  - Native nucleus pulposus tissue matrix promotes notochordal differentiation of
      human induced pluripotent stem cells with potential for treating intervertebral
      disc degeneration.
AB  - Native porcine nucleus pulposus (NP) tissue harbors a number of notochordal cells
      (NCs). Whether the native NP matrix supports the homeostasis of notochordal cells
      is poorly understood. We hypothesized the NP matrix alone may contain sufficient
      regulatory factors and can serve as stimuli to generate notochordal cells (NCs)
      from human pluripotent stem cells. NCs are a promising cell sources for cell
      based therapy to treat some types of intervertebral disc (IVD) degeneration. One
      major limitation of this emerging technique is the lack of available NCs as a
      potential therapeutic cell source. Human pluripotent stem cells derived from
      reprogramming or somatic cell nuclear transfer technique may yield stable and
      unlimited source for therapeutic use. We devised a new method to use porcine NP
      matrix to direct notochordal differentiation of human induced pluripotent stem
      cells (hiPSCs). The results showed that hiPSCs successfully differentiated into
      NC-like cells under the influence of devitalized porcine NP matrix. The NC-like
      cells expressed typical notochordal marker genes including brachyury (T),
      cytokeratin-8 (CK-8) and cytokeratin-18 (CK-18), and they displayed the ability
      to generate NP-like tissue in vitro, which was rich in aggrecan and collagen type
      II. These findings demonstrated the proof of concept for using native NP matrix
      to direct notochordal differentiation of hiPSCs. It provides a foundation for
      further understanding the biology of NCs, and eventually towards regenerative
      therapies for disc degeneration.

PMID- 24889906
TI  - Aortic valve type and calcification as assessed by transthoracic and
      transoesophageal echocardiography.
AB  - INTRODUCTION: Aortic valve calcification (AVC) may predict poor outcome. Bicuspid
      aortic valve (BAV) leads to several haemodynamic changes accelerating the
      progress of aortic valve (AV) disease. AIMS: To compare the diagnostic accuracy
      of transoesophageal echocardiography (TEE) and transthoracic echocardiography
      (TTE) in the assessment of aortic valve phenotype and degree of AVC, with intra
      operative evaluation as a reference. METHODS: We examined 169 patients (median
      age 65 years, 51 women) without significant coronary artery disease undergoing AV
      and/or aortic root surgery. TTE was performed within a week prior to surgery and
      TEE at the time of surgery. RESULTS: Compared with surgical AVC assessment,
      visual evaluation using a 5-grade scoring system and real-time images showed a
      higher correlation (TTE r = 0.83 and TEE r = 0.82) than visual (TTE r = 0.64 and
      TEE 0.63) or grey scale mean (GSMn) (TTE r = 0.63 and TEE r = 0.52) assessment of
      end-diastolic still frames. AVC assessment using real-time images showed high
      intraclass correlation coefficients (TTE 0.94 and TEE 0.93). With regard to BAV,
      TEE was superior to TTE with a higher interobserver agreement, sensitivity and
      specificity (0.86, 92% and 94% versus 0.57, 77% and 82%, respectively).
      CONCLUSION: Semi-quantitative AVC assessment of real-time cine loops from both
      TEE and TTE correlated well with intra-operative evaluation of AVC. Applying a
      predefined scoring system for AVC evaluation assures a high interobserver
      correlation. TEE was superior to TTE for evaluation of valve phenotype and should
      be considered when a diagnosis of BAV is clinically important.

PMID- 24889907
TI  - Aggregation behavior of Harmonia axyridis under non-wintering conditions.
AB  - The invasive multicolored Asian ladybeetle, Harmonia axyridis (Pallas)
      (Coleoptera: Coccinellidae), aggregates inside dwellings during winter to avoid
      cold weather. This adaptive behavior disturbs homeowners, because of the large
      numbers of individuals that aggregate, which induces allergic reactions. The
      migratory flight patterns of this species have been well documented, with
      individuals preferentially moving toward prominent and high color contrast
      elements. However, the factors involved in the selection of aggregation sites by
      this species have yet to be elucidated. Here, we evaluated the influence of (i)
      the density of individuals and (ii) the type of available shelters on decisions
      by H. axyridis to settle and aggregate under shelters. A dual choice bioassay
      conducted in the laboratory demonstrated the presence of mutual attraction to
      conspecifics. We also found that individuals preferentially settled under red
      covered shelters compared to transparent shelters, and that the type of shelter
      outweighed the effect of social interactions among conspecifics. Moreover, this
      experiment was performed under non-wintering conditions, providing the first
      evidence that aggregative behavior in this species can also occur under those
      specific conditions.

PMID- 24889908
TI  - Perforated duodenal diverticulum as an unusual sequelae of intestinal
      obstruction.

PMID- 24889909
TI  - In-office cup biopsy and laryngeal cytology versus operating room biopsy for the
      diagnosis of pharyngolaryngeal tumors: Efficacy and cost-effectiveness.
AB  - BACKGROUND: In-office biopsy is an effective technique to diagnose the nature of
      pharyngolaryngeal lesions. METHODS: We selected patients with pharyngolaryngeal
      lesions suspicious for malignancy. For in-office biopsy procedures, laryngeal
      cytology and direct laryngoscopy biopsy were performed, and diagnostic parameters
      and costs were estimated. RESULTS: Eighty-eight patients were selected for this
      study. For laryngeal cytology, sensitivity was 70.3% (95% confidence interval
      [CI] = 59.9% to 80.7%), specificity 100% with a positive predictive value of 100%
      and a negative predictive value of 50% (95% CI = 35.2% to 64.8%). In-office
      biopsy sensitivity was 81% (95% CI = 72.6% to 89.3%), specificity 100% with a
      positive predictive value of 100% and a negative predictive value of 20% (95% CI
      = 2.5% to 37.5%). At our hospital, the use of in-office biopsies as a first
      approach for diagnosis saves $50,140.80 U.S. per annum. CONCLUSION: In-office
      biopsy is a more affordable technique that enables histologic diagnosis of
      pharyngolaryngeal lesions in a large percentage of patients.

PMID- 24889910
TI  - Effects of case-based learning on communication skills, problem-solving ability,
      and learning motivation in nursing students.
AB  - The purpose of this study was to explore the effects of case-based learning on
      communication skills, problem-solving ability, and learning motivation in
      sophomore nursing students. In this prospective, quasi-experimental study, we
      compared the pretest and post-test scores of an experimental group and a
      nonequivalent, nonsynchronized control group. Both groups were selected using
      convenience sampling, and consisted of students enrolled in a health
      communication course in the fall semesters of 2011 (control group) and 2012
      (experimental group) at a nursing college in Suwon, South Korea. The two courses
      covered the same material, but in 2011 the course was lecture-based, while in
      2012, lectures were replaced by case-based learning comprising five authentic
      cases of patient-nurse communication. At post-test, the case-based learning group
      showed significantly greater communication skills, problem-solving ability, and
      learning motivation than the lecture-based learning group. This finding suggests
      that case-based learning is an effective learning and teaching method. 

PMID- 24889911
TI  - Assessment of changes in lentigo maligna during radiotherapy by in-vivo
      reflectance confocal microscopy: a pilot study.
AB  - BACKGROUND: Radiotherapy is an effective treatment for therapy of lentigo maligna
      (LM). OBJECTIVES: To investigate the usefulness of in-vivo reflectance confocal
      microscopy (RCM) in radiotherapy of LM and document the changes within the
      lesions during treatment. METHODS: A total of six lesions in six patients were
      investigated by RCM before, during and after radiotherapy. For diagnostic
      assessment three observers with experience in RCM diagnosis, blinded as to the
      stage of treatment, assessed the RCM images of each lesion and documented the
      findings by consensus. RESULTS: Epidermal disarray worsened in three patients
      during radiotherapy and superficial necrosis was observed in four patients. Large
      pagetoid round/dendritic cells decreased or even vanished during or after
      radiotherapy. Dilated vessels and apoptotic cells were seen in all patients
      during radiotherapy as well as an increase of inflammatory cells in the epidermis
      and dermis in most of the patients. Dendritic cells with small dendrites were
      observed during radiotherapy in all patients with an increase in number in three
      patients. Melanophages appeared in five patients at least once during the
      examination period. All RCM images were assessed correctly by the three
      observers. CONCLUSIONS: Reflectance confocal microscopy is a useful method to
      visualize changes during and after radiotherapy and might also be used for early
      detection of potential treatment failures. In addition, it might be helpful in
      planning radiotherapy.

PMID- 24889912
TI  - Guide to good practices to ensure privacy protection in secondary use of medical
      records.

PMID- 24889913
TI  - Parenchymal neurocysticercosis.

PMID- 24889914
TI  - Nephroureterectomy and ureteroneocystostomy in an alpaca with bilateral ectopic
      ureters diagnosed by computed tomographic excretory urography.
AB  - OBJECTIVE: To report diagnosis and treatment of urinary incontinence in a female
      Huacaya alpaca. STUDY DESIGN: Clinical case report. ANIMALS: Female intact
      Huacaya alpaca (n = 1) METHODS: Computed tomographic (CT) excretory urography and
      vaginourethrography were performed to diagnose the cause of urinary incontinence.
      RESULTS: Bilateral ectopic ureters and left hydronephrosis and hydroureter were
      diagnosed. Left nephroureterectomy and right ureteroneocystostomy were performed
      with subsequent resolution of clinical signs. Pyelonephritis was identified by
      culture of the resected left kidney. CONCLUSIONS: CT excretory urography was
      helpful in the diagnosis of bilateral ectopic ureters in an alpaca and provided
      information for surgical planning. Surgical repair by ureteroneocystostomy and
      unilateral nephroureterectomy was successful in resolving clinical signs.

PMID- 24889915
TI  - Review of therapeutic drug monitoring of anticancer drugs part 1--cytotoxics.
AB  - Most anticancer drugs are characterised by a steep dose-response relationship and
      narrow therapeutic window. Inter-individual pharmacokinetic (PK) variability is
      often substantial. The most relevant PK parameter for cytotoxic drugs is the area
      under the plasma concentration versus time curve (AUC). Thus it is somewhat
      surprising that therapeutic drug monitoring (TDM) is still uncommon for the
      majority of agents. Goals of the review were to assess the rationale for more
      widely used TDM of cytotoxics in oncology. There are several reasons why TDM has
      never been fully implemented into daily oncology practice. These include
      difficulties in establishing appropriate concentration target ranges, common use
      of combination chemotherapies for many tumour types, analytical challenges with
      prodrugs, intracellular compounds, the paucity of published data from
      pharmacological trials and 'Day1 = Day21' administration schedules. There are
      some specific situations for which these limitations are overcome, including high
      dose methotrexate, 5-fluorouracil infusion, mitotane and some high dose
      chemotherapy regimens. TDM in paediatric oncology represents an important
      challenge. Established TDM approaches includes the widely used anticancer agents
      carboplatin, busulfan and methotrexate, with 13-cis-retinoic acid also recently
      of interest. Considerable effort should be made to better define concentration
      effect relationships and to utilise tools such as population PK/PD models and
      comparative randomised trials of classic dosing versus pharmacokinetically guided
      adaptive dosing. There is an important heterogeneity among clinical practices and
      a strong need to promote TDM guidelines among the oncological community.

PMID- 24889916
TI  - BRCA1 gene promoter methylation status in high-grade serous ovarian cancer
      patients--a study of the tumour Bank ovarian cancer (TOC) and ovarian cancer
      diagnosis consortium (OVCAD).
AB  - BACKGROUND: Mutations in BRCA1/2 genes are involved in the pathogenesis of breast
      and ovarian cancer. Inactivation of these genes can also be mediated by
      hypermethylation of CpGs in the promoter regions. Aim of this study was to
      analyse the clinical impact of BRCA1 promoter gene methylation status in a
      homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients. METHODS:
      The cohort included 257 primary HGSOC patients treated by cytoreduction and
      platinum-based chemotherapy. DNA was extracted from fresh frozen tissue samples.
      BRCA1 gene promoter methylation rate was assessed using polymerase chain reaction
      (PCR). RESULTS: 14.8% of patients presented hypermethylation within a selected
      region of the BRCA1 promoter. The rate of hypermethylation was significantly
      higher in younger patients (20.8% hypermethylation in the age group ? 58 years
      versus 8.7% hypermethylation in the age group >58 years; p = 0.008). Optimal
      tumour debulking could be reached in 63% of patients, without significant
      differences in the extent of residual disease with respect to the methylation
      status. No impact of BRCA1 gene promoter methylation status on progression free-
      and overall-survival rates was found. No significant differences within BRCA1
      promoter methylation status between primary and metastatic tissue could be
      observed. These results on BRCA1 promoter methylation status were also confirmed
      in a subgroup of 107 patients found negative for BRCA1 exon 11 mutations.
      CONCLUSIONS: Our data suggest that BRCA1 methylation determines the earlier onset
      of HGSOC. Furthermore our study supports the idea that BRCAness is not only due
      to mutations but also to epigenetic changes in BRCA1 promoter gene.

PMID- 24889917
TI  - Transport and Golgi organisation protein 1 is a novel tumour progressive factor
      in oral squamous cell carcinoma.
AB  - Transport and Golgi organisation protein 1 (TANGO), also known as MIA3, belongs
      to the melanoma inhibitory activity (MIA) gene family. Although MIA acts as an
      oncogene, MIA2 and TANGO have a tumour-suppressive function in several
      malignancies; accordingly, the role and function of the MIA gene family in
      tumours remain controversial. Here the roles of TANGO were investigated in oral
      squamous cell carcinoma (OSCC). We analysed expression and function of TANGO in
      human OSCC cell lines. TANGO expression was also examined in 171 cases of primary
      OSCC by immunohistochemistry and statistically assessed the correlation between
      TANGO positivity and the clinicopathological parameters including vessel density.
      By TANGO knockdown in OSCC cells, the growth and invasion were repressed and
      apoptosis was induced. Activities of platelet-derived growth factor beta
      polypeptide (PDGFB) and Neuropilin2 were inhibited by TANGO knockdown. TANGO
      immunoreactivity was detected in 35.1% (60/171) cases of OSCC. TANGO expression
      was strongly associated with tumour progression, nodal metastasis, clinical stage
      and number of blood or lymph vessels in OSCC. Patients showing TANGO-expression
      fared significantly worse disease-free survival than cases without TANGO
      expression. These findings suggest that TANGO might promote angiogenesis and
      lymphangiogenesis by upregulation of PDGFB and Neuropilin2 in OSCC. 

PMID- 24889918
TI  - Blocking PI3K/Akt signaling attenuates metastasis of nasopharyngeal carcinoma
      cells through induction of mesenchymal-epithelial reverting transition.
AB  - In the present study, we evaluated the role of phosphatidylinositol-3 OH
      kinase/protein kinase B (PI3K/Akt) signaling on changes to epithelial-to
      mesenchymal reverting transition (EMrT) in nasopharyngeal carcinoma (NPC).
      Protein expression levels of p-Akt (Ser473), and the epithelial-to-mesenchymal
      transition (EMT) markers E-cadherin, vimentin, alpha smooth muscle actin (alpha
      SMA), were examined in clinical samples from 130 cases of undifferentiated non
      keratinizing NPC, and 20 cases of benign nasopharyngitis. The relationship
      between protein expression levels and the statue of NPC lymph node metastasis was
      analyzed. The poorly-differentiated NPC cell line CNE2Z was treated with various
      concentrations of the PI3K inhibitor, LY294002, and western blotting and
      quantitative polymerase chain reaction assays were used to analyze the activation
      of PI3K/Akt signaling and expression of E-cadherin, vimentin and alpha-SMA. The
      ability of cellular migration and invasion was assessed using Transwell assays.
      The in vivo effects of LY294002 on metastasis and expression of EMT markers in
      CNE2Z cells was evaluated using tumor xenograft experiments. The expression
      levels of p-Akt (Ser473) in NPC samples were higher than those in
      nasopharyngitis. There were reduced levels of membrane E-cadherin protein
      expression, and increased cytosol vimentin and alpha-SMA expression levels in NPC
      samples compared with those in nasopharyngitis samples. High expression levels of
      p-Akt (Ser473), vimentin, and alpha-SMA, and low expression levels of E-cadherin
      were positively associated with lymph node metastasis of NPC cells. Treating
      CNE2Z cells with LY294002 inhibited p-Akt (Ser473), vimentin and alpha-SMA
      expression but upregulated E-cadherin expression, leading to significantly
      attenuated cell invasion and migration. Administration of mice with LY294002
      resulted in upregulation of membrane E-cadherin, and downregulation of vimentin
      and alpha-SMA in CNE2Z xenografts, with reduced pulmonary metastasis. Our
      findings suggest that inhibiting the PI3K/Akt pathway using LY294002 attenuated
      NPC metastasis via induction of EMrT.

PMID- 24889919
TI  - Critical evaluation and modeling of algal harvesting using dissolved air
      flotation.
AB  - In this study, Chlorella zofingiensis harvesting by dissolved air flotation (DAF)
      was critically evaluated with regard to algal concentration, culture conditions,
      type and dosage of coagulants, and recycle ratio. Harvesting efficiency increased
      with coagulant dosage and leveled off at 81%, 86%, 91%, and 87% when chitosan,
      Al(3+) , Fe(3+) , and cetyl trimethylammonium bromide (CTAB) were used at dosages
      of 70, 180, 250, and 500 mg g(-1) , respectively. The DAF efficiency-coagulant
      dosage relationship changed with algal culture conditions. Evaluation of the
      influence of the initial algal concentration and recycle ratio revealed that,
      under conditions typical for algal harvesting, it is possible that the number of
      bubbles is insufficient. A DAF algal harvesting model was developed to explain
      this observation by introducing mass-based floc size distributions and a bubble
      limitation into the white water blanket model. The model revealed the importance
      of coagulation to increase floc-bubble collision and attachment, and the
      preferential interaction of bubbles with larger flocs, which limited the
      availability of bubbles to the smaller sized flocs. The harvesting efficiencies
      predicted by the model agree reasonably with experimental data obtained at
      different Al(3+) dosages, algal concentrations, and recycle ratios. Based on this
      modeling, critical parameters for efficient algal harvesting were identified.

PMID- 24889920
TI  - In vitro degradation, hemolysis, and cytocompatibility of PEO/PLLA composite
      coating on biodegradable AZ31 alloy.
AB  - Magnesium and its alloys have large potential as degradable and absorbable
      biomaterials because of their mechanical properties and biocompatibility.
      However, their corrosion resistance is usually inadequate especially in
      physiological environment, which limits their broad applications in biomedical
      areas. In this work, plasma electrolytic oxidized/poly(l-lactide) (PEO/PLLA)
      composite coating was successfully fabricated on biodegradable AZ31 alloy by
      combing PEO process and sealing with PLLA. The microstructure, elemental
      composition, and phase composition of the PEO/PLLA composite coating were
      investigated. The in vitro degradation of the PEO/PLLA composite coating in
      simulated body fluid (SBF) was also systematically evaluated. The results
      revealed that the PEO/PLLA composite coating improved the corrosion resistance of
      AZ31 alloy significantly. The corrosion potential shifted from -1.663V to more
      positive position -1.317 V and the corrosion current density was reduced with six
      order of magnitude. The Mg(2+) ions, hydrogen release, and pH value change of
      solution caused by degradation were all decreased significantly. Moreover, the
      PEO process played a critical role in sustaining the integrity of the implant in
      long-term service. The result of hemolysis test showed that the PEO/PLLA
      composite coating vested AZ31 alloy a low hemolysis ratio (0.806 +/- 0.771)%,
      which is much lower than the safe value of 5% according to ISO 10993-4. For the
      cytocompatibility test, compared with bare AZ31 alloy and PEO coating, MC3T3-E1
      cells showed much better adhesion and proliferation on the PEO/PLLA composite
      coating with nearly 4-fold increase of cells after 7-day cultivation, indicating
      that the PEO/PLLA composite coating has good biocompatibility for biomedical
      applications.

PMID- 24889921
TI  - Clinical applicability of rapid thrombelastography and functional fibrinogen
      thrombelastography to adult liver transplantation.
AB  - Unlike kaolin thrombelastography (k-TEG), the clinical utility of rapid
      thrombelastography (r-TEG) and functional fibrinogen thrombelastography (FF-TEG)
      has not been tested in liver transplantation (LT). These thrombelastography
      techniques were simultaneously performed at the time of the skin incision (the
      baseline) and 30 minutes after graft reperfusion (III + 30) for 27 consecutive
      adult LT patients. k-TEG and r-TEG parameters [alpha angle (alpha) and maximum
      amplitude of the clot (MA)] were compared in addition to the assay time.
      Estimated FF-TEG fibrinogen levels were compared with plasma fibrinogen
      measurements. At the baseline, the values of Spearman's correlation coefficient
      (r) between k-TEG and r-TEG were moderate for alpha (r = 0.40, P = 0.06) and
      strong for MA (r = 0.90, P < 0.01). At III + 30, r was 0.46 (P < 0.05) for alpha
      and 0.80 (P < 0.01) for MA. The average time required to measure MA via r-TEG was
      decreased in comparison with k-TEG [from 29.7 to 21.6 minutes at the baseline (a
      22% reduction) and from 29.6 to 22.9 minutes at III + 30 (a 23% reduction)]. FF
      TEG correlated strongly with the plasma fibrinogen level at the baseline (r =
      0.90, P < 0.01); however, FF-TEG overestimated the fibrinogen level at III + 30
      (r = 0.58, P = 0.01). In conclusion, in adult LT, r-TEG correlates with k-TEG
      strongly for MA but only moderately for alpha. FF-TEG estimates the plasma
      fibrinogen level well at the baseline; however, it must be interpreted with
      caution because of its overestimation after graft reperfusion when the plasma
      fibrinogen level often decreases to less than 100 mg/dL.

PMID- 24889922
TI  - Transcriptional profiling predicts overwhelming homology of Schwann cells,
      olfactory ensheathing cells, and Schwann cell-like glia.
AB  - Schwann cells (SCs), olfactory ensheathing cells (OECs), and central nervous
      system Schwann cell-like glia (SG) represent a group of nerve growth factor
      receptor p75 (NGFR)-positive cells, originating from different tissues. Because
      of their pro-regenerative capacities, these cells are subjects in experimental
      transplantation-based therapies of spinal cord trauma. The objective of this
      study was to compare the transcriptomes of uninfected and canine distemper virus
      infected OECs, SCs, SG and fibroblasts (FBs) derived from four beagle dogs and
      cultured under identical conditions in vitro, employing canine genome 2.0 arrays
      (Affymetrix). Here, we observed a complete lack of transcriptional differerences
      between OECs and SG, a high similarity of OECs/SG to SCs, and a marked difference
      of SCs and OECs/SG towards FBs. Differentially expressed genes possibly involved
      in the maintenance of cell type-specific identity included an up-regulation of
      HOXD8 and HOXC4 in SCs, and an up-regulation of CNTNAP2 and EFEMP1 in OECs/SG. We
      identified cell type-specific biomarkers employing supervised clustering with a K
      nearest-neighbors algorithm and correlation-based feature selection. Thereby AQP1
      and SCRG1 were predicted to be the most powerful biomarkers distinguishing SCs
      from OECs/SG. Immunofluorescence confirmed a higher expression of SCRG1 in OECs
      and SG, and conversely a higher expression of AQP1 in SCs in vitro. Furthermore,
      canine and murine olfactory nerves showed SCRG1-positive, AQP1-negative OECs
      and/or axons, whereas sciatic nerves displayed multifocal non-myelinated, AQP1
      positive, SCRG1-negative cells. Conclusively, OECs/SG are suggested to be a
      uniform cell type differing only in the tissue of origin and highly related to
      SCs.

PMID- 24889923
TI  - A pharmacogenetic study of ABCB1 polymorphisms and cyclosporine treatment
      response in patients with psoriasis in the Greek population.
AB  - Psoriasis affects 2-3% of the population, causing significant morbidity and
      financial burden. Immunosuppressive drugs such as cyclosporine are first line
      systemic therapies for moderate-to-severe forms. However, patients exhibit
      heterogeneity in their response to therapy, possibly due to genetic factors. The
      aim of the present study was to assess the ABCB1 T-129C, G1199A, C1236T, G2677T
      and C3435T single-nucleotide polymorphisms (SNPs) as candidate predictive markers
      of response to cyclosporine treatment in 84 psoriasis patients. 62% of the
      patients were defined as responders and 38% as nonresponders. All SNPs complied
      with Hardy-Weinberg equilibrium. SNP and haplotype analyses were performed to
      access responsiveness to treatment. Association analysis revealed statistically
      significant association of SNP 3435 T with negative response (P=0.0075), a result
      that was further validated in haplotype analysis. This study is the first in the
      field of the pharmacogenetics of cyclosporine in psoriasis whose results merit
      further exploitation in larger independent cohorts. 

PMID- 24889924
TI  - Use of activity monitors for assessment of pruritus in an acute model of canine
      atopic dermatitis.
AB  - BACKGROUND: We developed a canine model of acute atopic dermatitis to evaluate
      the potential of compounds to treat pruritus and skin lesions induced in
      Dermatophagoides farinae (Df)-sensitized dogs. HYPOTHESIS/OBJECTIVES: The aim was
      to investigate the effectiveness of long-term recording activity monitors to
      assess pruritus induced by allergen challenges. ANIMALS: Thirty-two Df-sensitized
      laboratory dogs. METHODS: In two blinded crossover studies, 28 Df-sensitized dogs
      were challenged on 3 days with a Df slurry applied to clipped abdominal skin.
      Dogs were treated with a positive control (prednisolone 1 mg/kg once daily for 5
      days, starting 1 day before challenge) or left untreated; all were fitted with
      activity monitors. To confirm pruritus, a parallel study with four dogs was
      conducted, filming the dogs before and during challenge and assessing the film
      for pruritic behaviour. RESULTS: The activity of dogs treated with prednisolone
      was significantly lower between 00.00 and 03.00 h and between 03.00 and 06.00 h
      compared with untreated dogs (repeated-measures ANCOVA; P < 0.0001). To determine
      whether the recorded night-time activity corresponded to pruritic manifestations,
      we compared activity monitor and video recordings of four dogs for two periods
      (16.30-20.30 and 24.00-03.00 h) before and during a Df challenge. The correlation
      between night-time activity monitor activity and observed pruritic behaviour was
      highly significant (test of correlation coefficient versus zero: r = 0.57, P <
      0.0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Determination of night-time
      activity with activity monitors after allergen challenge appears to be an
      objective and practical way to assess pruritus in this experimental model of
      canine atopic dermatitis.

PMID- 24889925
TI  - Matrix-assisted peptide synthesis on nanoparticles.
AB  - We report a new method for multistep peptide synthesis on polymeric nanoparticles
      of differing sizes. Polymeric nanoparticles were functionalized via their
      temporary embedment into a magnetic inorganic matrix that allows multistep
      peptide synthesis. The matrix is removed at the end of the process for obtaining
      nanoparticles functionalized with peptides. The matrix-assisted synthesis on
      nanoparticles was proved by generating various biologically relevant peptides.

PMID- 24889926
TI  - Focal bird species and risk assessment approach for nonagricultural grassland
      scenarios in Central Europe.
AB  - The European Food Safety Authority (EFSA) guideline on risk assessment identifies
      pesticide exposure scenarios for nontarget wildlife; however, this scheme is not
      applicable to nonagricultural grassland. For example, different habitats and
      human utilization on golf courses attract bird communities that differ from those
      found in agricultural fields with annual crop cycles. The present study
      determined focal bird species for amenity grasslands such as golf courses
      following the EFSA guideline. Based on published data and bird surveys, a total
      of 102 species were found on 13 golf courses in Central Europe. Approximately 58%
      of the species were recorded on >20% of the golf course and were classified as
      focal species candidates. Common kestrel (Falco tinnunculus), common linnet
      (Carduelis cannabina), wood pigeon (Columba palumbus), yellowhammer (Emberiza
      citrinella), white wagtail (Motacilla alba), and gray heron (Ardea cinerea) are
      the most adequate candidate focal species for exposure scenarios of carnivorous,
      granivorous, herbivorous, omnivorous, insectivorous, and piscivorous birds,
      respectively. Candidate species were verified on 3 golf courses in southwestern
      Germany in spring 2012. Observations on feeding behavior identified the main
      foraging areas of focal species. The results of the field work combined with data
      from the literature identified reliable exposure scenarios to assess the risk of
      pesticides to birds found on golf courses.

PMID- 24889928
TI  - Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and
      inflammatory cytokine secretion in vitro and in vivo.
AB  - Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell
      invasion, survival and metastasis in several types of cancers. However, the
      expression of TLR4 in patients with non-small cell lung cancer (NSCLC) and its
      biological function in the development and progression of NSCLC have not been
      elucidated to date. Here, we sought to characterize the expression of TLR4 in
      patients with NSCLC and to investigate the biological roles of TLR4 in lung
      metastasis, cell invasion and survival. In this study, we found that TLR4
      expression was elevated in most patients with NSCLC, and its expression levels
      correlated with key pathological characteristics, including tumor
      differentiation, stage and metastasis. Our data also showed that downregulation
      of TLR4 expression using an RNA silencing approach in A549 tumor cells
      significantly suppressed cell proliferation, cell migration and cell invasion,
      and induced tumor apoptosis in vitro, and suppressed tumor growth in vivo. In
      addition, we also found that downregulation of TLR4 expression significantly
      decreased cell TNF-alpha and IL-6 levels. Furthermore, we found that knockdown of
      TLR4 was able to significantly suppress constitutive phosphorylation of Akt and
      PI3K, which may contribute to the inhibition of tumor growth. These data suggest
      that TLR4 plays an important role in tumorigenic properties of human NSCLC, and
      that RNA interference-directed targeting of TLR4 could be used as a potential
      anticancer therapeutic target in NSCLC.

PMID- 24889927
TI  - Apoptosis of alcohol-exposed human placental cytotrophoblast cells is downstream
      of intracellular calcium signaling.
AB  - BACKGROUND: Apoptosis is induced by ethanol (EtOH) in human placental trophoblast
      cells, possibly disrupting placentation and contributing to intrauterine growth
      restriction in fetal alcohol spectrum disorder (FASD). EtOH induces programmed
      cell death in several embryonic tissues by raising intracellular Ca(2+) .
      Therefore, the role of Ca(2+) signaling in EtOH-induced apoptosis was examined
      using human first trimester cytotrophoblast cell lines, examining the hypothesis
      that apoptosis is dependent on intracellular Ca(2+) signaling. METHODS: Using HTR
      8/SVneo and SW.71 cytotrophoblast cell lines, real-time intracellular Ca(2+)
      concentration was monitored by fluo-4 epifluorescence microscopy and apoptosis
      was assessed by flow cytometry of cells fluorescently labeled for DNA
      fragmentation (TUNEL) and annexin V binding. RESULTS: Intracellular Ca(2+)
      concentrations increased synchronously in all cells within 10 seconds of exposure
      to 50 mM EtOH, but not at lower EtOH concentrations (10 to 25 mM) incapable of
      inducing apoptosis. Trophoblast cells treated with inhibitors of Ca(2+) signaling
      (BAPTA-AM, U73122, xestospongin D, BAPTA, SKF-96365) produced no intracellular
      Ca(2+) transients after exposure to 50 mM EtOH and were protected from cell death
      induced by EtOH. CONCLUSIONS: EtOH-induced apoptosis in human cytotrophoblast
      cells, identified by DNA fragmentation and externalized phosphatidylserine, was
      dependent upon Ca(2+) signaling. Both intracellular Ca(2+) mobilization and
      extracellular Ca(2+) influx were required, as well as phosphatidylinositol
      signaling. Inhibition by SKF-96365 suggests that the capacitative Ca(2+) entry
      mechanism that utilizes TRPC channels was activated by EtOH. Apoptosis occurs
      downstream of Ca(2+) signaling in trophoblasts and may contribute to placental
      insufficiency and poor fetal growth associated with FASD.

PMID- 24889929
TI  - Extensive nevus comedonicus involving the palm: questionable role of the
      pilosebaceous unit in pathogenesis.
AB  - A 10-year-old boy had multiple grouped pits with black plugs arranged along the
      lines of Blaschko on his left chest, arm, and palm. Involvement of the palms is
      rarely reported in the literature. Recent reports have described mosaic acneiform
      conditions that could share pathogenetic mechanisms with nevus comedonicus. We
      briefly review the literature on mosaic conditions with acneiform lesions
      including nevus comedonicus. 

PMID- 24889930
TI  - Duration of residence and disease occurrence among refugees and family reunited
      immigrants: test of the 'healthy migrant effect' hypothesis.
AB  - OBJECTIVES: The 'healthy migrant effect' (HME) hypothesis postulates that health
      selection has a positive effect on migrants' health outcomes, especially in the
      first years after migration. We examined the potential role of the HME by
      assessing the association between residence duration and disease occurrence.
      METHODS: We performed a historical prospective cohort study. We included migrants
      who obtained residence permits in Denmark between 1 January 1993 and 31 December
      2010 (n = 114,331). Occurrence of severe conditions was identified through
      linkage to the Danish National Patient Register. Hazard Ratios (HRs) were
      modelled for disease incidence by residence duration since arrival (0-5 years; 0
      10 years; 0-18 years) adjusting for age and sex. RESULTS: Compared with Danish
      born individuals, refugees and family reunited immigrants had lower HRs of stroke
      and breast cancer within 5 years after arrival; however, HRs increased at longer
      follow-up. For example, HRs of stroke among refugees increased from 0.77 (95% CI:
      0.66; 0.91) to 0.96 (95% CI: 0.88; 1.05). For ischaemic heart disease (IHD) and
      diabetes, refugees and family reunited migrants had higher HRs within 5 years
      after arrival, and most HRs had increased by end of follow-up. For example, HRs
      of IHD among family reunited migrants increased from 1.29 (95% CI: 1.17; 1.42) to
      1.43 (95% CI: 1.39; 1.52). In contrast, HRs for TB and HIV/AIDS showed a
      consistent decrease over time. CONCLUSION: Our analyses of the effect of duration
      of residence on disease occurrence among migrants imply that, when explaining
      migrants' advantageous health outcomes, the ruling theory of the HME should be
      used with caution, and other explanatory models should be included.

PMID- 24889931
TI  - Rapid determination of corticosterone in mouse plasma by ultra fast liquid
      chromatography-tandem mass spectrometry.
AB  - Major depressive disorder is a severe, life-threatening and highly prevalent
      psychiatric disorder. A high percentage of people suffering from depression are
      characterized by hyperactivity of the hypothalamic-pituitary-adrenal axis,
      resulting in plasma glucocorticoid (cortisol in human and corticosterone in
      rodent) elevations. Glucocorticoid is a critical molecule in the onset of
      pathology of depression. A simple, highly sensitive and specific method based on
      ultra-fast liquid chromatography-tandem mass spectrometry method has been
      developed for the quantitation of corticosterone in mouse plasma for the first
      time, which provides technical support for the high-throughput measurement for
      clinical determination of corticosterone in biological samples. Samples were
      spiked with methanol to precipitate the protein, and then chromatographed on an
      Agilent Zorbax Eclipse Plus C18 (100 * 2.1 mm,1.8 um) column by linear gradient
      elution with methanol and 0.1% formic acid as the mobile phase within 5 min. The
      detection of corticosterone was performed on ultra-fast liquid chromatography
      triple quadrupole tandem mass spectrometry in the positive ion. The ions [M +
      H](+) m/z 347.2 -> m/z 311.1 for corticosterone and [M + H](+) m/z 363.2 -> m/z
      327.2 for hydrocortisone (internal standard) were used for quantitative
      determination. The lower quantification limit for corticosterone was 1 ng/mL. The
      validated method was successfully applied to the quantitation of corticosterone
      in mouse plasma.

PMID- 24889934
TI  - Cone size is related to branching architecture in conifers.
AB  - The relationship between branch diameter and leaf size has been widely used to
      understand how vegetative resources are allocated in plants. Branching
      architecture influences reproductive allocation as well, but fewer studies have
      explored this relationship at broad phylogenetic or ecological scales. In this
      study, we tested whether pollen-producing and seed-producing cone size scales
      with branch diameter in conifers, a diverse and globally distributed lineage of
      nonflowering seed plants. Branch diameter and cone size were analyzed using
      multiple regression models and evolutionary models of trait evolution for a data
      set of 293 extant conifer species within an explicit phylogenetic framework.
      Branch diameter is a strong predictor of cone size across conifer species,
      particularly for pollen cones and dry seed cones. However, these relationships
      are complex in detail because leaf morphology and seed dispersal biology
      influence the specific ways in which they are expressed. The ubiquity and
      strength of these scaling relationships across conifers suggest that reproductive
      and vegetative morphologies are coupled in the group, and it is therefore
      difficult to disentangle the evolution of cone size from the evolution of
      branching architecture. 

PMID- 24889932
TI  - Iron-responsive chromatin remodelling and MAPK signalling enhance adhesion in
      Candida albicans.
AB  - Recent cumulative data show that various transcription factors are recruited to
      the chromatin in an iron-responsive manner to affect diverse cellular functions
      in the pathogenic fungus Candida albicans. Here we identified groups of iron
      responsive genes in C. albicans by chromatin remodelling analysis at gene
      promoters, using micrococcal nuclease (MNase) digestion followed by deep
      sequencing. Chromatin in the promoter regions of iron uptake and utilization
      genes showed repressed and active configuration, respectively, under iron-replete
      conditions. GO Term enrichment analysis of genes with differentially remodelled
      chromatin, in respective promoter locales, suggested that many genes involved in
      adhesion are also iron-responsive. C. albicans was observed to be more self
      adherent (twofold increase) and formed higher biofilm mass (77% increase) in the
      presence of iron. Furthermore, we identified various known and novel adhesion
      related genes with iron-dependent active chromatin profiles that are indicative
      of potential upregulation under iron-replete conditions. Transcription factor
      Cph1 that is activated upon Cek1 phosphorylation also showed an active chromatin
      profile under iron-replete conditions and cells showed iron-responsive Cek1 MAPK
      phosphorylation in the presence of iron. Thus, iron affects diverse biological
      functions by modulating chromatin profiles of large gene sets and by signalling
      through Cek1 MAPK in C. albicans. 

PMID- 24889933
TI  - Patient involvement in research programming and implementation: A responsive
      evaluation of the Dialogue Model for research agenda setting.
AB  - BACKGROUND: The Dialogue Model for research agenda-setting, involving multiple
      stakeholders including patients, was developed and validated in the Netherlands.
      However, there is little insight into whether and how patient involvement is
      sustained during the programming and implementation of research agendas. AIM: To
      understand how the Dialogue Model can be optimised by focusing on programming and
      implementation, in order to stimulate the inclusion of (the perspectives of)
      patients in research. METHODS: A responsive evaluation of the programming and
      implementation phases of nine agenda-setting projects that had used the Dialogue
      Model for agenda-setting was conducted. Fifty-four semi-structured interviews
      were held with different stakeholders (patients, researchers, funding agencies).
      Three focus groups with patients, funding agencies and researchers (16
      participants) were organized to validate the findings. RESULTS: Patient
      involvement in programming and implementation of the research agendas was
      limited. This was partly related to poor programming and implementation, partly
      to pitfalls in earlier phases of the agenda-setting. Optimization of the Dialogue
      Model is possible by attending to the nature of the agenda and its intended use
      in earlier phases. Attention should also be given to the ambassadors and intended
      users of agenda topics. Support is needed during programming and implementation
      to organize patient involvement and adapt organizational structures like review
      procedures. In all phases the attitude to patient involvement, stakeholder
      participation, especially of researchers, and formal and informal relationships
      between parties need to be addressed to build a strong relationship with a shared
      goal. CONCLUSION: Patient involvement in agenda-setting is not automatically
      followed by patient involvement in programming and implementation. More attention
      should be paid, in earlier stages, to the attitude and engagement of researchers
      and funding agencies.

PMID- 24889935
TI  - Experimental evolution of an emerging plant virus in host genotypes that differ
      in their susceptibility to infection.
AB  - This study evaluates the extent to which genetic differences among host
      individuals from the same species condition the evolution of a plant RNA virus.
      We performed a threefold replicated evolution experiment in which Tobacco etch
      potyvirus isolate At17b (TEV-At17b), adapted to Arabidopsis thaliana ecotype Ler
      0, was serially passaged in five genetically heterogeneous ecotypes of A.
      thaliana. After 15 passages we found that evolved viruses improved their fitness,
      showed higher infectivity and stronger virulence in their local host ecotypes.
      The genome of evolved lineages was sequenced and putative adaptive mutations
      identified. Host-driven convergent mutations have been identified. Evidences
      supported selection for increased translational efficiency. Next, we sought for
      the specificity of virus adaptation by infecting all five ecotypes with all 15
      evolved virus populations. We found that some ecotypes were more permissive to
      infection than others, and that some evolved virus isolates were more
      specialist/generalist than others. The bipartite network linking ecotypes with
      evolved viruses was significantly nested but not modular, suggesting that hard-to
      infect ecotypes were infected by generalist viruses whereas easy-to-infect
      ecotypes were infected by all viruses, as predicted by a gene-for-gene model of
      infection. 

PMID- 24889936
TI  - Parp-1 genetic ablation in Ela-myc mice unveils novel roles for Parp-1 in
      pancreatic cancer.
AB  - Pancreatic cancer has a dismal prognosis and is currently the fourth leading
      cause of cancer-related death in developed countries. The inhibition of poly(ADP
      ribose) polymerase-1 (Parp-1), the major protein responsible for poly(ADP
      ribosy)lation in response to DNA damage, has emerged as a promising treatment for
      several tumour types. Here we aimed to elucidate the involvement of Parp-1 in
      pancreatic tumour progression. We assessed Parp-1 protein expression in normal,
      preneoplastic and pancreatic tumour samples from humans and from K-Ras- and c-myc
      driven mouse models of pancreatic cancer. Parp-1 was highly expressed in acinar
      cells in normal and cancer tissues. In contrast, ductal cells expressed very low
      or undetectable levels of this protein, both in a normal and in a tumour context.
      The Parp-1 expression pattern was similar in human and mouse samples, thereby
      validating the use of animal models for further studies. To determine the in vivo
      effects of Parp-1 depletion on pancreatic cancer progression, Ela-myc-driven
      pancreatic tumour development was analysed in a Parp-1 knock-out background. Loss
      of Parp-1 resulted in increased tumour necrosis and decreased proliferation,
      apoptosis and angiogenesis. Interestingly, Ela-myc:Parp-1(-/-) mice displayed
      fewer ductal tumours than their Ela-myc:Parp-1(+/+) counterparts, suggesting that
      Parp-1 participates in promoting acinar-to-ductal metaplasia, a key event in
      pancreatic cancer initiation. Moreover, impaired macrophage recruitment can be
      responsible for the ADM blockade found in the Ela-myc:Parp-1(-/-) mice. Finally,
      molecular analysis revealed that Parp-1 modulates ADM downstream of the Stat3
      MMP7 axis and is also involved in transcriptional up-regulation of the MDM2,
      VEGFR1 and MMP28 cancer-related genes. In conclusion, the expression pattern of
      Parp-1 in normal and cancer tissue and the in vivo functional effects of Parp-1
      depletion point to a novel role for this protein in pancreatic carcinogenesis and
      shed light into the clinical use of Parp-1 inhibitors.

PMID- 24889939
TI  - Building on success with new fields to conquer.

PMID- 24889940
TI  - Open enrollment, take two.

PMID- 24889938
TI  - Estrogen promotes stemness and invasiveness of ER-positive breast cancer cells
      through Gli1 activation.
AB  - BACKGROUND: Although long-term estrogen (E2) exposure is associated with
      increased breast cancer (BC) risk, and E2 appears to sustain growth of BC cells
      that express functional estrogen receptors (ERs), its role in promoting BC stem
      cells (CSCs) remains unclear. Considering that Gli1, part of the Sonic hedgehog
      (Shh) developmental pathway, has been shown to mediate CSCs, we investigated
      whether E2 and Gli1 could promote CSCs and epithelial-mesenchymal transition
      (EMT) in ER+ BC cell lines. METHODS: We knocked down Gli1 in several BC cells
      using a doxycycline-controlled vector, and compared Gli1-knockdown cells and
      Gli1+ cells in behavior and expression of ER, Gli1, ALDH1 (BC-CSC marker), Shh,
      Ptch1 (Shh receptor) and SOX2, Nanog and Bmi-1 (CSC-associated transcriptions
      factors), using PCR; tissue microarrays, western blot; chromatin
      immunoprecipitation q-PCR, confocal immunofluorescence microscopy; fluorescence
      activated cell sorting; annexin-flow cytometry (for apoptosis); mammosphere
      culture; and colony formation, immunohistochemistry, Matrigel and wound-scratch
      assays. RESULTS: Both mRNA and protein expressions of ER correlated with those of
      Gli1 and ALDH1. E2 induced Gli1 expression only in ER+ BC cells. E2 promoted CSC
      renewal, invasiveness and EMT in ER+/Gli1+ cells but not in Gli1-knockdown cells.
      CONCLUSIONS: Our results indicate that estrogen acts via Gli1 to promote CSC
      development and EMT in ER+ BC cells. These findings also imply that Gli1 mediates
      cancer stem cells, and thus could be a target of a novel treatment for ER+ breast
      cancer.

PMID- 24889937
TI  - Combination budesonide/formoterol inhaler as maintenance and reliever therapy in
      Maori with asthma.
AB  - BACKGROUND AND OBJECTIVE: There are significant health disparities between Maori
      and non-Maori with asthma, a pattern seen between other ethnic populations. This
      study investigates outcomes for Maori in a randomized controlled trial (RCT) of
      combination budesonide/formoterol inhaler therapy in asthma. METHODS: This 24
      week multicentre RCT recruited 303 adult asthma patients, 44 of whom were Maori.
      Participants were randomized to the single combination budesonide/formoterol
      inhaler as maintenance and reliever therapy ('SMART') regimen or 'standard'
      regimen (combination budesonide/formoterol inhaler for maintenance and salbutamol
      as reliever). Outcomes included patterns of beta-agonist inhaler use including
      'high use' of reliever therapy (>8 actuations of budesonide/formoterol in excess
      of four maintenance doses per day for SMART and >16 actuations per day of
      salbutamol for standard). Differences in outcomes for Maori versus non-Maori were
      assessed using an interaction term between ethnicity and treatment. RESULTS: With
      adjustment for ethnicity, the SMART group had fewer days of high use (relative
      rate (RR) 0.57 (95% confidence interval (CI): 0.38-0.85)), days of high use
      without medical review within 48 h (RR 0.49 (95% CI: 0.32-0.75)) and severe
      exacerbations (RR 0.54 (95% CI: 0.36-0.81)) compared with standard. The magnitude
      of the benefit from the SMART regimen was similar in Maori and non-Maori.
      Regardless of treatment regimen, Maori demonstrated more days of high use, high
      use without medical review and underuse of maintenance therapy. CONCLUSIONS: The
      SMART regimen has a favourable risk/benefit profile in Maori. Days of high use,
      days of high use without medical review and underuse of maintenance treatment
      were greater in Maori, regardless of treatment regimen.

PMID- 24889941
TI  - Switching to less expensive blindness drug could save medicare part B $18 billion
      over a ten-year period.
AB  - The biologic drugs bevacizumab and ranibizumab have revolutionized treatment of
      diabetic macular edema and neovascular age-related macular degeneration, leading
      causes of blindness. Ophthalmologic use of these drugs has increased and now
      accounts for roughly one-sixth of the Medicare Part B drug budget. The two drugs
      have similar efficacy and potentially minor differences in adverse-event rates;
      however, at $2,023 per dose, ranibizumab costs forty times more than bevacizumab.
      Using modeling methods, we predict ten-year (2010-20) population-level costs and
      health benefits of using bevacizumab and ranibizumab. Our results show that if
      all patients were treated with the less expensive bevacizumab instead of current
      usage patterns, savings would amount to $18 billion for Medicare Part B and
      nearly $5 billion for patients. With an additional $6 billion savings in other
      health care expenses, the total savings would be almost $29 billion. Altering
      patterns of use with these therapies by encouraging bevacizumab use and hastening
      approval of biosimilar therapies would dramatically reduce spending without
      substantially affecting patient outcomes.

PMID- 24889943
TI  - Medicare home health payment reform may jeopardize access for clinically complex
      and socially vulnerable patients.
AB  - The Affordable Care Act directed Medicare to update its home health prospective
      payment system to reflect more recent data on costs and use of services-an
      exercise known as rebasing. As a result, the Centers for Medicare and Medicaid
      Services will reduce home health payments 3.5 percent per year in the period 2014
      17. To determine the impact that these reductions could have on beneficiaries
      using home health care, we examined the Medicare reimbursement margins and the
      use of services in a national sample of 96,621 episodes of care provided by
      twenty-six not-for-profit home health agencies in 2011. We found that patients
      with clinically complex conditions and social vulnerability factors, such as
      living alone, had substantially higher service delivery costs than other home
      health patients. Thus, the socially vulnerable patients with complex conditions
      represent less profit-lower-to-negative Medicare margins-for home health
      agencies. This financial disincentive could reduce such patients' access to care
      as Medicare payments decline. Policy makers should consider the unique
      characteristics of these patients and ensure their continued access to Medicare's
      home health services when planning rebasing and future adjustments to the
      prospective payment system. 

PMID- 24889942
TI  - A simple change to the Medicare Part D low-income subsidy program could save $5
      billion.
AB  - Medicare Part D provides a subsidy to beneficiaries with incomes below 150
      percent of the federal poverty level. Enrollees with the low-income subsidy
      accounted for 75 percent of the $60 billion in total federal Part D spending in
      2013. The government randomly assigns any new beneficiary who automatically
      qualifies for the subsidy, or who successfully applies for it without indicating
      a preferred plan, to a stand-alone Part D plan whose premium is equal to or below
      the average premium for the basic Part D benefit in the region. We used an
      intelligent reassignment algorithm and 2008-09 Part D drug use and spending data
      to match enrollees to available plans according to their medication needs. We
      found that such a reassignment approach could have saved the federal government
      over $5 billion in 2009, for mean government savings of $710 (median: $368) per
      enrollee with a low-income subsidy. Implementing that simple change to reassign
      beneficiaries would have also lowered the proportion of prescriptions that
      required utilization review from 29 percent to 20 percent, and the proportion of
      prescriptions with quantity limits from 27 percent to 19 percent.

PMID- 24889944
TI  - Patients' preferences explain a small but significant share of regional variation
      in medicare spending.
AB  - This study assessed the extent to which differences in patients' preferences
      across geographic areas explained differences in traditional fee-for-service
      Medicare spending across Dartmouth Atlas of Health Care Hospital Referral Regions
      (HRRs). Preference measures were based on results of a survey that asked patients
      questions about their physicians, their own health status, and the care they
      would want in their last six months of life. We found that patients' preferences
      explained 5 percent of the variation across HRRs in total Medicare spending. In
      comparison, supply factors, such as the number of physicians, specialists, and
      hospital beds, explained 23 percent, and patients' health and income explained 12
      percent. We also explored the relative importance of preferences in determining
      three components of total spending: spending at the end of life, inpatient
      spending, and spending on physician services. Relative to supply factors, health,
      and income, patients' preferences explained the largest share of variation in end
      of-life spending and the smallest share of variation in spending on physician
      services. We conclude that variation in preferences contributes to differences
      across areas in Medicare spending. Medicare policy must consider both supply
      factors and patients' preferences in deciding how much to accommodate area
      variation in spending and the extent to which that variation should be subsidized
      by taxpayers. 

PMID- 24889945
TI  - First national survey of ACOs finds that physicians are playing strong leadership
      and ownership roles.
AB  - The extent to which physicians lead, own, and govern accountable care
      organizations (ACOs) is unknown. However, physicians' involvement in ACOs will
      influence how clinicians and patients perceive the ACO model, how effective these
      organizations are at improving quality and costs, and how future ACOs will be
      organized. From October 2012 to May 2013 we fielded the National Survey of
      Accountable Care Organizations, the first such survey of public and private ACOs.
      We found that 51 percent of ACOs were physician-led, with another 33 percent
      jointly led by physicians and hospitals. In 78 percent of ACOs, physicians
      constituted a majority of the governing board, and physicians owned 40 percent of
      ACOs. The broad reach of physician leadership has important implications for the
      future evolution of ACOs. It seems likely that the challenge of fundamentally
      changing care delivery as the country moves away from fee-for-service payment
      will not be accomplished without strong, effective leadership from physicians. 

PMID- 24889946
TI  - Attention to surgeons and surgical care is largely missing from early medicare
      accountable care organizations.
AB  - The Affordable Care Act supports the growth of accountable care organizations
      (ACOs) as a potentially powerful model for health care delivery and payment. The
      model focuses on primary care. However, surgeons and other specialists have a
      large role to play in caring for ACOs' patients. No studies have yet investigated
      the role of surgical care in the ACO model. Using case studies and a survey, we
      examined the early experience of fifty-nine Medicare-approved ACOs in providing
      surgical care. We found that ACOs have so far devoted little attention to
      surgical care. Instead, they have emphasized coordinating care for patients with
      chronic conditions and reducing unnecessary hospital readmissions and ED visits.
      In the years to come, ACOs will likely focus more on surgical care. Some ACOs
      have the ability to affect surgical practice patterns through referral pressures,
      but local market conditions may limit ACOs' abilities to alter surgeons'
      behavior. Policy makers, ACO administrators, and surgeons need to be aware of
      these trends because they have the potential to affect the surgical care provided
      to ACO patients as well as the success of ACOs themselves. 

PMID- 24889947
TI  - Patient-centered medical home initiative produced modest economic results for
      Veterans Health Administration, 2010-12.
AB  - In 2010 the Veterans Health Administration (VHA) began a nationwide initiative
      called Patient Aligned Care Teams (PACT) that reorganized care at all VHA primary
      care clinics in accordance with the patient-centered medical home model. We
      analyzed data for fiscal years 2003-12 to assess how trends in health care use
      and costs changed after the implementation of PACT. We found that PACT was
      associated with modest increases in primary care visits and with modest decreases
      in both hospitalizations for ambulatory care-sensitive conditions and outpatient
      visits with mental health specialists. We estimated that these changes avoided
      $596 million in costs, compared to the investment in PACT of $774 million, for a
      potential net loss of $178 million in the study period. Although PACT has not
      generated a positive return, it is still maturing, and trends in costs and use
      are favorable. Adopting patient-centered care does not appear to have been a
      major financial risk for the VHA.

PMID- 24889948
TI  - Disproportionate-share hospital payment reductions may threaten the financial
      stability of safety-net hospitals.
AB  - Safety-net hospitals rely on disproportionate-share hospital (DSH) payments to
      help cover uncompensated care costs and underpayments by Medicaid (known as
      Medicaid shortfalls). The Affordable Care Act (ACA) anticipates that insurance
      expansion will increase safety-net hospitals' revenues and will reduce DSH
      payments accordingly. We examined the impact of the ACA's Medicaid DSH reductions
      on California public hospitals' financial stability by estimating how total DSH
      costs (uncompensated care costs and Medicaid shortfalls) will change as a result
      of insurance expansion and the offsetting DSH reductions. Decreases in
      uncompensated care costs resulting from the ACA insurance expansion may not match
      the act's DSH reductions because of the high number of people who will remain
      uninsured, low Medicaid reimbursement rates, and medical cost inflation. Taking
      these three factors into account, we estimate that California public hospitals'
      total DSH costs will increase from $2.044 billion in 2010 to $2.363-$2.503
      billion in 2019, with unmet DSH costs of $1.381-$1.537 billion.

PMID- 24889950
TI  - Factors associated with high levels of spending for younger dually eligible
      beneficiaries with mental disorders.
AB  - The Affordable Care Act focused attention on how conflicting rules and payment
      arrangements in Medicare and Medicaid can produce high costs and fragmented care
      for people who are dually eligible for the two programs. Nearly half of such dual
      eligibles have severe and persistent mental disorders. Using Medicare data for
      the period 2006-09, we examined factors that were associated with high levels of
      spending for dual eligibles younger than sixty-five with a mental disorder. We
      found that these beneficiaries were nearly twice (1.86 times) as expensive as
      young dual eligibles who did not have a mental disorder. We identified functional
      limitations, multiple chronic conditions, and substance use disorders as being
      associated with high levels of spending in this subpopulation. We conclude that
      case management that coordinated medical, mental health, and substance use
      treatment along with psychosocial rehabilitation services could yield savings,
      primarily to the Medicare program. Because only Medicaid pays for case management
      and psychosocial rehabilitation services, Medicaid spending may need to rise if
      overall savings are to be realized. 

PMID- 24889949
TI  - Medicaid enrollment policy increased smoking cessation among pregnant women but
      had no impact on birth outcomes.
AB  - Cigarette smoking during pregnancy is an important cause of poor maternal and
      infant health outcomes in the population eligible for Medicaid. These outcomes
      may be avoided or attenuated by timely, high-quality prenatal care. Using data
      from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment
      Monitoring System for the period 2004-10, we examined the effects of two optional
      state Medicaid enrollment policies on smoking cessation, preterm birth, and
      having an infant who was small for gestational age. We used a natural experiment
      to compare outcomes before and after nineteen states adopted either of the two
      policies. The first policy, presumptive eligibility, permits women to receive
      prenatal care while their Medicaid application is pending. Its adoption led to a
      7.7-percentage-point increase in smoking cessation but did not reduce adverse
      birth outcomes. The second policy, the unborn-child option, permits states to
      provide coverage to pregnant women who cannot document their citizenship or
      residency. Its adoption was not significantly associated with any of the three
      outcomes. The presumptive-eligibility enrollment policy will continue to be an
      important tool for promoting timely prenatal care and smoking cessation. 

PMID- 24889951
TI  - Restrictions on pharmaceutical detailing reduced off-label prescribing of
      antidepressants and antipsychotics in children.
AB  - The treatment of pediatric depression is controversial because it includes
      substantial prescribing of drugs for uses that have not been approved by the Food
      and Drug Administration ("off label") and are not evidence based. Some academic
      medical centers (AMCs) restrict "detailing" by pharmaceutical sales
      representatives, or the promoting of drugs directly to physicians via sales
      calls, to reduce the effect of such marketing on physician prescribing. With data
      from thirty-one geographically diverse AMCs and their affiliated hospitals, we
      used a difference-in-differences model to estimate the effect of anti-detailing
      policies on off-label prescribing of antidepressants and antipsychotics by
      pediatricians and by child and adolescent psychiatrists in the period January
      2006-June 2009. We found that after the introduction of such policies,
      prescriptions for off-label use of promoted drugs fell by 11 percent, consistent
      with the ongoing presence of off-label marketing to physicians. Prescriptions for
      on-label use of promoted drugs fell by 34 percent after the adoption of the
      policies. Conversely, prescriptions for on-label use of nonpromoted drugs rose by
      14 percent, and those for off-label use of nonpromoted drugs rose by 35 percent.
      These results suggest that pharmaceutical sales representatives promoted drugs
      not approved for pediatric use and that policies that restrict detailing by those
      representatives reduced such off-label prescribing.

PMID- 24889952
TI  - Estimating the health and economic burden of cancer among those diagnosed as
      adolescents and young adults.
AB  - Adolescent and young adult cancer survivors-those who were ages 15-39 at their
      first cancer diagnosis-have important health limitations. These survivors are at
      risk for higher health care expenditures and lost productivity, compared to
      adults without a history of cancer. Using Medical Expenditure Panel Survey data,
      we present nationally representative estimates of the economic burden among
      people who were diagnosed with cancer in adolescence or young adulthood. Our
      findings demonstrate that surviving cancer at this age is associated with a
      substantial economic burden. Compared to adults without a history of cancer,
      adolescent and young adult cancer survivors had excess annual medical
      expenditures of $3,170 per person and excess annual productivity losses of $2,250
      per person. Multifaceted prevention strategies, including education and sustained
      intervention programs to ensure access to lifelong risk-based follow-up care, may
      be effective ways to improve the economic outcomes associated with cancer
      survivorship in this population. 

PMID- 24889953
TI  - Ending SNAP subsidies for sugar-sweetened beverages could reduce obesity and type
      2 diabetes.
AB  - To reduce obesity and type 2 diabetes rates, lawmakers have proposed modifying
      Supplemental Nutrition Assistance Program (SNAP) benefits to encourage healthier
      food choices. We examined the impact of two proposed policies: a ban on using
      SNAP dollars to buy sugar-sweetened beverages; and a subsidy in which for every
      SNAP dollar spent on fruit and vegetables, thirty cents is credited back to
      participants' SNAP benefit cards. We used nationally representative data and
      models describing obesity, type 2 diabetes, and determinants of food consumption
      among a sample of over 19,000 SNAP participants. We found that a ban on SNAP
      purchases of sugar-sweetened beverages would be expected to significantly reduce
      obesity prevalence and type 2 diabetes incidence, particularly among adults ages
      18-65 and some racial and ethnic minorities. The subsidy policy would not be
      expected to have a significant effect on obesity and type 2 diabetes, given
      available data. Such a subsidy could, however, more than double the proportion of
      SNAP participants who meet federal vegetable and fruit consumption guidelines. 

PMID- 24889954
TI  - CDC central-line bloodstream infection prevention efforts produced net benefits
      of at least $640 Million during 1990-2008.
AB  - The prevention of central line-associated bloodstream infections in patients in
      hospital critical care units has been a target of efforts by the Centers for
      Disease Control and Prevention (CDC) since the 1960s. We developed a historical
      economic model to measure the net economic benefits of preventing these
      infections in Medicare and Medicaid patients in critical care units for the
      period 1990-2008-a time when reductions attributable to federal investment
      resulted primarily from CDC efforts-using the cost perspective of the federal
      government as a third-party payer. The estimated net economic benefits ranged
      from $640 million to $1.8 billion, with the corresponding net benefits per case
      averted ranging from $15,780 to $24,391. The per dollar rate of return on the
      CDC's investments ranged from $3.88 to $23.85. These findings suggest that
      investments in CDC programs targeting other health care-associated infections
      also have the potential to produce savings by lowering Medicare and Medicaid
      reimbursements. 

PMID- 24889955
TI  - Regulatory and cost barriers are likely to limit biosimilar development and
      expected savings in the near future.
AB  - In March 2010 Congress established an abbreviated Food and Drug Administration
      approval pathway for biosimilars-drugs that are very similar but not identical to
      a reference biological product and cost less. Because bringing biosimilars to the
      market currently requires large investments of money, fewer biosimilars are
      expected to enter the biologics market than has been the case with generic drugs
      entering the small-molecule drug market. Additionally, given the high regulatory
      hurdles to obtaining interchangeability-which would allow pharmacists to
      substitute a biosimilar for its reference product, subject to evolving state
      substitution laws-most biosimilars will likely compete as therapeutic
      alternatives instead of as therapeutic equivalents. In other words, biosimilars
      will need to compete with their reference product on the basis of quality; price;
      and manufacturer's reputation with physicians, insurers, and patient groups.
      Biosimilars also will face dynamic competition from new biologics in the same
      therapeutic class-including "biobetters," which offer incremental improvements on
      reference products, such as extended duration of action. The prospects for
      significant cost savings from the use of biosimilars appear to be limited for the
      next several years, but their use should increase over time because of both
      demand- and supply-side factors.

PMID- 24889956
TI  - 'Big push' to reduce maternal mortality in Uganda and Zambia enhanced health
      systems but lacked a sustainability plan.
AB  - In the past decade, "big push" global health initiatives financed by
      international donors have aimed to rapidly reach ambitious health targets in low
      income countries. The health system impacts of these efforts are infrequently
      assessed. Saving Mothers, Giving Life is a global public-private partnership that
      aims to reduce maternal mortality dramatically in one year in eight districts in
      Uganda and Zambia. We evaluated the first six to twelve months of the program's
      implementation, its ownership by national ministries of health, and its effects
      on health systems. The project's impact on maternal mortality is not reported
      here. We found that the Saving Mothers, Giving Life initiative delivered a large
      "dose" of intervention quickly by capitalizing on existing US international
      health assistance platforms, such as the President's Emergency Plan for AIDS
      Relief. Early benefits to the broader health system included greater policy
      attention to maternal and child health, new health care infrastructure, and new
      models for collaborating with the private sector and communities. However, the
      rapid pace, external design, and lack of a long-term financing plan hindered
      integration into the health system and local ownership. Sustaining and scaling up
      early gains of similar big push initiatives requires longer-term commitments and
      a clear plan for transition to national control. 

PMID- 24889957
TI  - 'Nothing is broken': for an injured doctor, quality-focused care misses the mark.

PMID- 24889959
TI  - Graduate education for primary care physicians.

PMID- 24889960
TI  - Graduate medical education: the authors reply.

PMID- 24889961
TI  - Screening for HIV in jails and prisons.

PMID- 24889962
TI  - Screening inmates for HIV: the authors reply.

PMID- 24889963
TI  - Health literacy and connected health.

PMID- 24889964
TI  - Mass spectrometric analysis of protein tyrosine nitration in aging and
      neurodegenerative diseases.
AB  - This review highlights the significance of protein tyrosine nitration (PTN) in
      signal transduction pathways, the progress achieved in analytical methods, and
      the implication of nitration in the cellular pathophysiology of aging and age
      related neurodegenerative diseases. Although mass spectrometry of nitrated
      peptides has become a powerful tool for the characterization of nitrated
      peptides, the low stoichiometry of this modification clearly necessitates the use
      of affinity chromatography to enrich modified peptides. Analysis of nitropeptides
      involves identification of endogenous, intact modification as well as chemical
      conversion of the nitro group to a chemically reactive amine group and further
      modifications that enable affinity capture and enhance detectability by altering
      molecular properties. In this review, we focus on the recent progress in chemical
      derivatization of nitropeptides for enrichment and mass analysis, and for
      detection and quantification using various analytical tools. PTN participates in
      physiological processes, such as aging and neurodegenerative diseases.
      Accumulation of 3-nitrotyrosine has been found to occur during the aging process;
      this was identified through mass spectrometry. Further, there are several studies
      implicating the presence of nitrated tyrosine in age-related diseases such as
      Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

PMID- 24889965
TI  - Network-based identification of key proteins involved in apoptosis and cell cycle
      regulation.
AB  - OBJECTIVES: Cancer cells differ from normal body cells in their ability to divide
      indefinitely and to evade programmed cell death. Crosstalk between apoptosis and
      cell cycle processes promotes balance between proliferation and death, and limits
      population growth and survival of cells. However, intricate relationships between
      them and how they are able to manipulate the fate of cancer cells still remain to
      be clarified. Identification of key factors involved in both apoptosis and cell
      cycle regulation may help to address this problem. MATERIALS AND METHODS:
      Identification of such key proteins was carried out, using a series of
      bioinformatics methods, such as network construction and key protein
      identification. RESULTS: In this study, we computationally constructed human
      apoptotic/cell cycle-related protein-protein interactions (PPIs) networks from
      five experimentally supported protein interaction databases, and further
      integrated these high-throughput data sets into a Naive Bayesian model to predict
      protein functional connections. On the basis of modified apoptotic/cell cycle
      related PPI networks, we calculated and ranked all protein members involved in
      apoptosis and cell cycle regulation. Our results not only identified some already
      known key proteins such as p53, Rb, Myc and Src but also found that the
      proteasome, Cullin family members, kinases and transcriptional repressors play
      important roles in regulating apoptosis and the cell cycle. Furthermore, we found
      that the top 100 proteins ranked by PeC were enriched in some pathways such as
      those of cancer, the proteasome, the cell cycle and Wnt signalling. CONCLUSIONS:
      We constructed the global human apoptotic/cell cycle related PPI network based on
      five online databases, and a Naive Bayesian model. In addition, we systematically
      identified apoptotic/cell cycle related key proteins in cancer cells. These
      findings may uncover intricate relationships between apoptosis and cell cycle
      processes and thus provide further new clues towards future anticancer drug
      discovery.

PMID- 24889966
TI  - Photochemistry of RuII 4,4'-bi-1,2,3-triazolyl (btz) complexes: crystallographic
      characterization of the photoreactive ligand-loss intermediate trans
      [Ru(bpy)(kappa2-btz)(kappa1-btz)(NCMe)]2+.
AB  - We report the unprecedented observation and unequivocal crystallographic
      characterization of the meta-stable ligand loss intermediate solvento complex
      trans-[Ru(bpy)(kappa(2) -btz)(kappa(1) -btz)(NCMe)](2+) (1 a) that contains a
      monodentate chelate ligand. This and analogous complexes can be observed during
      the photolysis reactions of a family of complexes of the form
      [Ru({NN})(btz)(2)](2+) (1 a-d: btz=1,1'-dibenzyl-4,4'-bi-1,2,3-triazolyl; {NN}=a)
      2,2'-bipyridyl (bpy), b) 4,4'-dimethyl-2,2'-bipyridyl (dmbpy), c) 4,4'-dimethoxy
      2,2'-bipyridyl (dmeobpy), d) 1,10-phenanthroline (phen)). In acetonitrile
      solutions, 1 a-d eventually convert to the bis-solvento complexes trans
      [Ru({NN})(btz)(NCMe)(2)](2+) (3 a-d) along with one equivalent of free btz, in a
      process in which the remaining coordinated bidentate ligands undergo a new
      rearrangement such that they become coplanar. X-ray crystal structure of 3 a and
      3 d confirmed the co-planar arrangement of the {NN} and btz ligands and the trans
      coordination of two solvent molecules. These conversions proceed via the observed
      intermediate complexes 2 a-d, which are formed quantitatively from 1 a-d in a
      matter of minutes and to which they slowly revert back on being left to stand in
      the dark over several days. The remarkably long lifetime of the intermediate
      complexes (>12 h at 40  degrees C) allowed the isolation of 2 a in the solid
      state, and the complex to be crystallographically characterized. Similarly to the
      structures adopted by complexes 3 a and d, the bpy and kappa(2) -btz ligands in 2
      a coordinate in a square-planar fashion with the second monodentate btz ligand
      coordinated trans to an acetonitrile ligand.

PMID- 24889968
TI  - Elevated perioperative serum CA 19-9 levels are independent predictors of poor
      survival in patients with resectable cholangiocarcinoma.
AB  - BACKGROUND AND OBJECTIVES: Identification of prognostic markers is important to
      establish a perioperative therapeutic strategy for resectable cholangiocarcinoma
      (CC). The aim of this study was to investigate whether perioperative serum
      carbohydrate antigen 19-9 (CA19-9) levels can predict survival of patients who
      underwent surgical resection for CC. METHODS: The study included 106 patients who
      underwent surgical resection for CC. Serum CA19-9 levels were measured
      preoperatively after biliary drainage and postoperatively about 4 weeks after
      surgery. The association of clinicopathological factors (including perioperative
      serum CA19-9 levels) with overall survival (OS) was analyzed with univariate and
      multivariate analyses. RESULTS: Differences in OS were significant between groups
      divided on the basis of two preoperative CA19-9 cutoff values (in U/ml) of 37 and
      200 and three postoperative CA19-9 cutoff values (in U/ml) of 37, 100, and 200.
      In multivariate analysis, absence of postoperative adjuvant chemotherapy (P =
      0.002), lymph node metastasis (P = 0.0002), preoperative CA19-9 (>= 200 IU/ml) (P
      = 0.03), and postoperative CA19-9 (>= 37 IU/ml) (P < 0.0001) were identified as
      independent predictors of poor OS. CONCLUSION: Both pre- and postoperative serum
      CA19-9 levels predict the survival of patients with resectable CC, and may
      contribute to the establishment of a new therapeutic strategy.

PMID- 24889967
TI  - Assessment of Plasmodium falciparum PfMDR1 transport rates using Fluo-4.
AB  - Mutations in the multidrug resistance transporter of Plasmodium falciparum PfMDR1
      have been implicated to play a significant role in the emergence of worldwide
      drug resistance, yet the molecular and biochemical mechanisms of this transporter
      are not well understood. Although it is generally accepted that drug resistance
      in P. falciparum is partly associated with PfMDR1 transport activity situated in
      the membrane of the digestive vacuole, direct estimates of the pump rate of this
      transport process in the natural environment of the intact host-parasite system
      have never been analysed. The fluorochrome Fluo-4 is a well-documented surrogate
      substrate of PfMDR1 and has been found to accumulate by actively being
      transported into the digestive vacuole of several parasitic strains. In the
      present study, we designed an approach to use Fluo-4 fluorescence uptake as a
      measure of compartmental Fluo-4 concentration accumulation in the different
      compartments of the host-parasite system. We performed a 'reverse Fluo-4 imaging'
      approach to relate fluorescence intensity to changes in dye concentration rather
      than Ca(2+) fluctuations and were able to calculate the overall rate of transport
      for PfMDR1 in Dd2 parasites. With this assay, we provide a powerful method to
      selectively measure the effect of PfMDR1 mutations on substrate transport
      kinetics. This will be of high significance for future compound screening to test
      for new drugs in resistant P. falciparum strains.

PMID- 24889969
TI  - Simulated climate warming alters phenological synchrony between an outbreak
      insect herbivore and host trees.
AB  - As the world's climate warms, the phenologies of interacting organisms in
      seasonally cold environments may advance at differing rates, leading to
      alterations in phenological synchrony that can have important ecological
      consequences. For temperate and boreal species, the timing of early spring
      development plays a key role in plant-herbivore interactions and can influence
      insect performance, outbreak dynamics, and plant damage. We used a field-based,
      meso-scale free-air forest warming experiment (B4WarmED) to examine the effects
      of elevated temperature on the phenology and performance of forest tent
      caterpillar (Malacosoma disstria) in relation to the phenology of two host trees,
      aspen (Populus tremuloides) and birch (Betula papyrifera). Results of our 2-year
      study demonstrated that spring phenology advanced for both insects and trees,
      with experimentally manipulated increases in temperature of 1.7 and 3.4  degrees
      C. However, tree phenology advanced more than insect phenology, resulting in
      altered phenological synchrony. Specifically, we observed a decrease in the time
      interval between herbivore egg hatch and budbreak of aspen in both years and
      birch in one year. Moreover, warming decreased larval development time from egg
      hatch to pupation, but did not affect pupal mass. Larvae developed more quickly
      on aspen than birch, but pupal mass was not affected by host species. Our study
      reveals that warming-induced phenological shifts can alter the timing of
      ecological interactions across trophic levels. These findings illustrate one
      mechanism by which climate warming could mediate insect herbivore outbreaks, and
      also highlights the importance of climate change effects on trophic interactions.

PMID- 24889970
TI  - What otolith microchemistry and stable isotope analysis reveal and conceal about
      anguillid eel movements across salinity boundaries.
AB  - Otolith microchemistry studies indicate that growth-phase (yellow stage)
      anguillid eels commonly shift at irregular intervals between fresh and saline
      waters, but this technique has not detected regular seasonal migrations across
      salinity zones. We tested the ability of otolith microchemistry and stable
      isotope analysis to detect migrations of American eels (Anguilla rostrata)
      between salinity boundaries in two small stream-estuary systems in Canada's Bay
      of Fundy. Although the two methods showed concordant classifications of recent
      residence history, most eels caught in fresh water in spring (68.8-89.7%) and
      fall (78.8-83.3%) showed microchemical and isotopic signatures that reflected
      occupancy of saline waters. These eels were classified as migrants which had
      summered in saline waters and then migrated to freshwater wintering grounds where
      they retained their saline signatures. In summer, most eels (85.0-100.0%)
      captured in fresh and saline water had recent microchemical and isotopic
      signatures matching the habitat of capture. Our results suggest that lifetime
      otolith microchemistry profiles are unable to detect eel wintering migrations, a
      failure that is likely due to winter depression of otolith accretion. Elucidation
      of seasonal eel movements requires cross-seasonal and cross-site sampling for the
      microchemistry and stable isotope methods, or tagging studies. Seasonal saline
      fresh eel migrations may be more common than previously appreciated, underlining
      the need for conservation of both habitats, and connectivity between the two.

PMID- 24889972
TI  - The incidence of melanoma is increasing in the susceptible young Australian
      population.
AB  - The number of melanomas removed from Australians is increasing. Despite this, it
      has been reported that the incidence of melanoma is decreasing in the young
      Australian population. However, the denominator for these estimates includes
      individuals at low risk of melanoma, and the proportion of such individuals has
      changed over recent decades due to immigration. In this study, the incidence was
      calculated for the susceptible young population. Data from the Australian Bureau
      of Statistics were analysed to determine the number of people younger than 30
      years at low risk of developing melanoma in 1982 and 2009. Low risk people were
      defined as those born in Asia, the Pacific Islands, The Middle East, or Sub
      Saharan Africa, or had parents born in these regions. There was a significant
      increase in the number of young Australians at low risk for melanoma. If these
      people are not included when calculating the crude rate of melanoma, the rate
      increased from 5.9 per 100,000 in 1982 to 6.3 in 2009. If the estimated number of
      young Maoris and young Aborigines is excluded from the susceptible population,
      the crude rate increased from 6.0 per 100,000 in 1982 to 6.8 in 2009. This is the
      first calculation of the rate of melanoma for the susceptible young Australian
      population. 

PMID- 24889971
TI  - Distinct effects of Disabled-2 on transferrin uptake in different cell types and
      culture conditions.
AB  - Iron uptake by the transferrin (Tf)-transferrin receptor (TfR) complex is
      critical for erythroid differentiation. The mechanisms of TfR trafficking have
      been examined, but the adaptor proteins involved in this process are not fully
      elucidated. We have investigated the role of the adaptor protein, Disabled-2
      (Dab2), in erythroid differentiation and Tf uptake in the cells of hematopoietic
      lineage. Dab2 was upregulated in a time-dependent manner during erythroid
      differentiation of mouse embryonic stem cells and human K562 erythroleukemic
      cells. Attenuating Dab2 expression in K562 cells diminished TfR internalization
      and increased surface levels of TfR concomitantly with a decrease in Tf uptake
      and erythroid differentiation. Dab2 regulated Tf uptake of the suspended, but not
      adherent, cultures of K562 cells. In contrast, Dab2 is not involved in TfR
      trafficking in the HeLa cells with epithelial origin. These differential effects
      are Dab2-specific because attenuating the expression of adaptor protein 2 MU
      subunit inhibited the uptake of Tf regardless of culture condition. We offer
      novel insight of Dab2 function in iron uptake and TfR internalization for the
      suspended culture of hematopoietic lineage cells. 

PMID- 24889973
TI  - A correlation study of the expression of resistin and glycometabolism in muscle
      tissue after traumatic brain injury in rats.
AB  - OBJECTIVE: To investigate the expression pattern of resistin (RSTN) in skeletal
      muscle tissue and its influence on glycometabolism in rats with traumatic brain
      injury (TBI). METHODS: Seventy-eight SD rats were randomly divided into traumatic
      group (n=36), RSTN group (n=36) and sham operation group (n=6). Fluid percussion
      TBI model was developed in traumatic and RSTN groups and the latter received
      additional 1 mg RSTN antibody treatment for each rat. At respectively 12 h, 24 h,
      72 h, 1 w, 2 w, and 4 w after operation, venous blood was collected and the right
      hind leg skeletal muscle tissue was sampled. We used real-time PCR to determine
      mRNA expression of RSTN in skeletal muscles, western blot to determine RSTN
      protein expression and ELISA to assess serum insulin as well as fasting blood
      glucose (FBG) levels. Calculation of the quantitative insulin sensitivity check
      index (Q value) was also conducted. The above mentioned indicators and their
      correction were statistically analyzed. RESULTS: Compared with sham operation
      group, the RSTN expression in the skeletal muscle as well as serum insulin and
      FBG levels revealed significant elevation (P<0.05), and reduced Q value (P<0.05)
      in traumatic group. Single factor linear correlation analysis showed a
      significant negative correlation between RSTN expression and Q values (P<0.001)
      in traumatic group. CONCLUSION: The expression of RSTN has been greatly increased
      in the muscular tissue of TBI rats and it was closely related to the index of
      glycometabolism. RSTN may play an important role in the process of insulin
      resistance after TBI.

PMID- 24889974
TI  - Open reduction and internal fixation for displaced supracondylar fractures of the
      humerus in children with crossed K-wires via lateral approach.
AB  - OBJECTIVE: To assess the therapeutic results of open reduction and internal
      fixation with crossed K-wires via lateral approach for displaced supracondylar
      fractures of the humerus in children. METHODS: We prospectively followed 52
      children who presented with Gartland type 3 displaced supracondylar fractures of
      the humerus and were managed by open reduction and internal fixation with crossed
      K-wires via lateral approach.There were 37 male and 15 female patients; average
      age was 7.39 years. The most common mechanism of trauma was fall while playing
      (n=23), followed by fall from height (n=20), road traffic accidents (n=5) and
      fall from standing height (n=2). In 2 cases, mode of injury was not available.
      The mean follow-up was 12 months and patients were assessed according to Flynn's
      criteria. RESULTS: Lateral approach provided an excellent view of the lateral
      column between two nervous planes and enabled an anatomical reduction in all
      cases. Immobilizing the elbow at 90 degrees or more of flexion was not needed
      after cross K-wire fixation. Majority of patients regained full range of motion
      within 6 weeks of pin removal. Two patients had postoperative ulnar nerve
      injuries that resolved after pin removal. The common late complication of cubitus
      varus was not seen in any patient. Delayed presentation to the emergency
      department, repeated manipulations by bone setters and massage with edible oil
      were responsible for stiffness in 5 patients. Superficial pin tract infection was
      noted in 5 patients that resolved with dressings and antibiotics. No deep
      infection occurred. A detailed clinical examination and radiographic analysis was
      done at final follow-up. They included measurement of carrying angle and range of
      movements of both operated and normal sides, and radiographs of both upper limbs
      for comparison. According to Flynn's criteria, 90.4% patients showed satisfactory
      results. CONCLUSION: Lateral approach for open reduction and internal fixation of
      the widely-displaced supracondylar fracture of the humerus is safe and
      straightforward, ensuring anatomical reduction and excellent function. The
      approach is easy and familiar to most orthopedic surgeons in our setup.

PMID- 24889975
TI  - Modified Blair ankle fusion for ankle arthritis.
AB  - OBJECTIVE: To investigate the clinical outcome of modified Blair ankle fusion for
      ankle arthritis. METHODS: Between November 2009 and June 2012, 28 patients with
      ankle arthritis were treated, among whom 11 had obvious foot varus deformity, and
      17 were almost normal in appearance. There were 13 males and 15 females with an
      average age of 49.4 years (range, 23-67 years). The main symptoms included
      swelling, pain, and a limited range of motion of the ankles. The ankle joints
      functions were assessed by American Orthopedic Foot and Ankle Society (AOFAS)
      ankle and hindfoot score and visual analog scale (VAS) preoperatively and at 1
      year follow-up. RESULTS: Twenty-eight patients were followed up for 19.8 months
      on average (range, 1-2 years). Superficial wound infection occurred in 3 cases,
      and was cured after debridement; the other incisions healed by first intention
      without complications. All ankles were fused at 1 year follow-up after operation.
      The symptom was relieved completely in all patients at last follow-up without
      complication of implant failure, or nonunion. The postoperative AOFAS ankle and
      hindfoot score was 83.13+/-3.76, showing significant difference when compared
      with the preoperative score (45.38+/-3.21, P<0.01). VAS was significantly
      decreased from 8.01+/-0.63 to 2.31+/-1.05 at 1 year follow-up (P<0.05).
      CONCLUSION: Modified Blair ankle fusion has the advantages of high feasiblity,
      less cost and rigid fixation. It shows high reliability in pain relief and may
      obtain a good clinical effectiveness.

PMID- 24889976
TI  - Comparison of extramedullary and intramedullary devices for treatment of
      subtrochanteric femoral fractures at tertiary level center.
AB  - OBJECTIVE: The treatment of subtrochanteric fractures is challenging and
      treatment modalities and implants are constantly evolving. This study attempts to
      revisit and compare extramedullary vs. intramedullary devices in relatively young
      population. METHODS: Thirty patients with subtrochanteric fractures were enrolled
      and treated with extramedullary or intramedullary devices and follow-up continued
      one year for clinico-radiological assessment. RESULTS: The mean age of patients
      was 37.53 years. Most were males between 21-40 years. The dominant mode of injury
      was traffic accidents (66%). Fractures were classified according to Russell
      Taylor classification. Forty percent were Russell-Taylor type IA, 37% type IB and
      23% type IIA. Average time to surgery was 3.6 days from the time of admission to
      hospital. Mean duration of surgery was 45 minutes for intramedullary device
      (group A) and 105 minutes for extramedullary device (group B). Average blood loss
      was 100 ml in group A and 200 ml in group B. Mean duration of radiation exposure
      was 130 seconds and 140 seconds for groups A and B, while average duration of
      hospital stay was 12 days and 16 days respectively. Excellent results were seen
      in 47% of cases in group A and 33% of cases in group B. CONCLUSION:
      Intramedullary device is a reliable implant for subtrochanteric fractures. It has
      high rates of union with minimal soft-tissue damage. Intramedullary fixation has
      biological and biomechanical advantages, but surgery is technically demanding.
      Gradual learning and patience is needed to make this method truly rewarding.

PMID- 24889977
TI  - Comparison of a new single-donor human fibrin adhesive with suture for posterior
      tibial nerve repair in rat: biomechanical resistance and functional analysis.
AB  - OBJECTIVE: The use of fibrin adhesives has a broad background in nerve repair.
      Currently the suboptimal physical properties of single- donor fibrin adhesives
      have restricted their usage. The present experiment studies the performance and
      physical characteristics of a modified fibrin glue prepared from single-donor
      human plasma in the repair of posterior tibial nerve of rat. METHODS: Forty
      Wistar rats were divided into 5 groups; in the control group, tibial nerve was
      completely transected and no treatment was done, while in the four experimental
      groups the nerve stumps were reconnected by one suture, three sutures, one suture
      with fibrin glue and fibrin glue alone respectively. During 8 weeks of follow-up,
      Tibial Function Index was measured weekly and adhesive strength, inflammation and
      scar formation were assessed at the end of the study. RESULTS: Nerve stumps
      dehiscence rate and adhesive strength were similar in all experimental groups and
      significantly differed from control group (P<0.05). By the end of the eighth
      follow-up week, functional recovery of one and three sutures groups were
      significantly higher than groups in which fibrin glue was used for repair
      (P<0.05). The amount of inflammation and scar tissue formation was similar among
      all groups. CONCLUSION: The study results show that the prepared single-donor
      fibrin adhesive has acceptable mechanical properties which could provide required
      adhesiveness and hold nerve stumps in the long term; yet, we acknowledge that
      more studies are needed to improve functional outcome of single donor fibrin
      adhesive repair.

PMID- 24889978
TI  - A seven-year study on head injuries in infants, Iran---the changing pattern.
AB  - OBJECTIVE: Head injury (HI) is the leading cause of mortality and life-long
      disability in infants. Infants have different anatomical and pathophysiological
      brain structures from other age groups. The aim of this study was to survey
      infant HI patients admitted to Shahid Behest Hospital in Kashan, Iran from 2004
      to 2010, and to identify the causes of HIs in this age group. METHODS: In this
      retrospective study, all HI patients under the age of two who were hospitalized
      for more than 24 hours between January 2004 and January 2010 were enrolled in the
      study. Demographic, etiologic, and injury data were collected and a descriptive
      analysis was performed. RESULTS: Infants comprised 20.8% of all children (under
      15 years old) with HIs and 65.1% of the injuries occurred in the home. Falls were
      the most common cause of injury (63.4%). In hospital mortality was 6.6 per 100
      000 infants. A decreasing trend was seen in home events, but HIs caused by
      traffic accidents were increasing during the study period. The amount of HI
      infants resulting from car accidents has tripled from the years 2004 to 2010.
      CONCLUSION: Although home events and falling are the main causes of infant HIs
      and need attention, our study showed an increase of HIs caused by road traffic
      accidents, especially by car accidents, thus legislation for the implementation
      of protective equipment such as child safety seats and programs is urgently
      needed.

PMID- 24889979
TI  - Biological modalities for treatment of acute spinal cord injury: a pilot study
      and review of the literature.
AB  - OBJECTIVE: Paraplegia due to traumatic spinal cord injuries is one of the
      devastating effects of dorsolumbar vertebral fractures. Treatment modalities for
      such fractures, such as stabilization, have no effect on the neurological
      recovery. Thus, various pharmacological and biological treatment modalities have
      been used. The more recent trend of using autologous stem cells from the iliac
      crest has been used in some clinical trials with varying success. Thus, more
      clinical studies are required to study the effect of this novel approach METHODS:
      This is a prospective hospital-based cohort study (level IV). The study was
      conducted in the Dept. of Orthopaedics, University College of Medical Sciences
      and GTB Hospital, Delhi from November 2010 to March 2012. Ten patients who had
      sustained traumatic dorsolumbar vertebral fractures with complete paraplegia were
      recruited for this study. Under suitable anaesthesia, at the beginning of
      surgery, 100 ml of bone marrow was aspirated. This was centrifuged and buffy coat
      isolated and then transferred into a sterile tube and sent to the operating room
      on ice packs. After surgical decompression and stabilization, the buffy coat
      isolate was injected into the dural sleeve at the site of the injury using a 21G
      needle. All the patients were evaluated for neurological improvement using the
      American Spinal Injury Association (ASIA) score and Frankel grade at 6 weeks and
      3 months postoperatively. RESULTS: The evaluation at 6 weeks showed some
      improvement in terms of the ASIA scores in 2 patients but no improvements in
      their Frankel Grade. The other 8 patients showed no improvements in their ASIA
      scores or their Frankel Grades. The current pilot study has shown that there has
      been no improvement in most of the recipients of the transplant (n=8). Some
      patients (n=2) who did show some improvement in their sensory scores proved to be
      of no significant functional value as depicted by no change in their Frankel
      Grades. CONCLUSION: The outcome of current study shows that although this
      modality of treatment is safe for the patients, it provides no additional
      benefits on improvement of quality of life among these patients.

PMID- 24889980
TI  - Iraq-Iran chemical war: calendar, mortality and morbidity.
AB  - OBJECTIVES: To review the calendar, mortality and morbidity of Iraq-Iran chemical
      war among Iranians based on researchers'reports. METHODS: We used national and
      international databanks such as PubMed, ISI, Scopus, Irandoc and Iranmedex and
      studied 350 articles related to chemical agents and their effects on different
      organs. The main criteria for qualification of articles were relevancy
      orientation and being published in approved medical journals. RESULTS: The Iraqi
      army invaded to west and southwest Iran using chemical weapons such as nerve
      agents (NAs) and sulfur mustard (SM). Most victims were civilians including women
      and children. These attacks had imposed more than 150 types of diseases and
      complications on Iranians and the frequency of death was 2%-3%. Most reports were
      about respiratory problems and a few were in the domain of socio-economic
      damages. CONCLUSION: At present, 25 years after the end of war, the victims are
      faced with different complications induced by chemical agents and it is estimated
      that they will be continuously troubled by these problems in future.

PMID- 24889981
TI  - Gunshot (Pellets) injury to the maxillofacial complex: a case report.
AB  - Gunshot injuries are rather serious but uncommon type of trauma in India. A 45
      year-old male was presented with gunshot (pellets) embedded in the maxillofacial
      area for 22 years. There is no consensus in the literature whether to attempt
      their removal or leave them in situ. Our patient had no long-term sequela like
      infection, fistula formation, carcinogenesis or metal poisoning to date except
      for chill feeling on cold days. Management of this patient presented a dilemma in
      treatment in view of the effects of foreign bodies in the maxillofacial area. 

PMID- 24889983
TI  - An unusual cause of radial nerve palsy.
AB  - Neurapraxia frequently occurs following traction injury to the nerve
      intraoperatively, leading to radial nerve palsy which usually recovers in 5-30
      weeks. In our case, we had operated a distal one-third of humeral shaft fracture
      and fixed it with 4.5 mm limited contact dynamic compression plate. The distal
      neurovascular status of the limb was assessed postoperatively in the recovery
      room and was found to be intact and all the sensory-motor functions of the radial
      nerve were normal. On the second postoperative day, following the suction drain
      removal and dressing, patient developed immediate radial nerve palsy along with
      wrist drop. We reviewed the literature and found no obvious cause for the nerve
      palsy and concluded that it was due to traction injury to the radial nerve while
      removing the suction drain in negative pressure. 

PMID- 24889982
TI  - Multiple metallic foreign bodies accidentally detected in different body
      cavities: a case report.
AB  - We accidentally found an unusual case of a middle aged Tibetan woman who had
      eight metallic foreign bodies (eight needles) in her head, chest and abdomen.
      These needles were not related to any surgical intervention or trauma. The
      diagnosis "metallic foreign bodies" cannot usually be made in an acute setting.
      Some patients may present chronic symptoms, such as infection or pain. However,
      in some cases, the patients do not have any symptoms. 

PMID- 24889984
TI  - Spinal cord injury in Parkour sport (free running): a rare case report.
AB  - A 24-year-old male was transferred to the emergency department while being in the
      state of quadriplegia with a history of performing Parkour sport, which is also
      called double front flip. Neurological examination revealed that the patient's
      muscle power was 0/5 at all extremities. The patient did not show any sense of
      light touch or pain in his extremities. In radiological studies, cervical spine X
      ray and CT scan images showed C4-C5 subluxation with bilateral locked facets and
      spinal cord injury. The results of this very rare case study revealed that
      exercising Parkour sport without taking into account safety standards could
      result in irreversible injuries to the cervical spinal cord with fatal outcome. 

PMID- 24889985
TI  - Undiagnosed Hoffa fracture of medial femoral condyle presenting as chronic pain
      in a post-polio limb.
AB  - Isolated coronal fracture of medial femoral condyle with intact lateral femoral
      condyle is extremely rare. A high index of suspicion is necessary for early
      diagnosis especially in cases of undisplaced fractures. Here we report a case of
      medial Hoffa fracture in a post-polio limb presenting as chronic pain. Management
      of such fractures in limbs affected by late sequelae of poliomyelitis is
      particularly problematic in view of osteoporosis and osseous hypoplasia. The
      fracture was approached through medial parapatellar arthrotomy and fixation was
      done with cannulated cancellous screws in anteroposterior direction. Union was
      achieved at 16 weeks. 

PMID- 24889986
TI  - Triple plating of tibia in a complex bicondylar tibial plateau fracture.
AB  - High-energy tibial plateau fracture poses a significant challenge and difficulty
      for orthopaedic surgeons. Fracture of tibial plateau involves major weight
      bearing joint and may alter knee kinematics. Anatomic reconstruction of the
      proximal tibial articular surfaces, restoration of the limb axis (limb alignment)
      and stable fixation permitting early joint motion are the goals of the treatment.
      In cases of complex bicondylar tibial plateau fractures, isolated lateral plating
      is frequently associated with varus malalignment and better results have been
      obtained with bilateral plating through dual incisions. However sometimes a
      complex type of bicondylar tibial plateau fractures is encountered in which
      medial plateau has a biplaner fracture in posterior coronal plane as well as
      sagittal plane. In such fractures it is imperative to fix the medial plateau with
      buttressing in both planes. One such fracture pattern of the proximal tibia
      managed by triple plating through dual posteromedial and anterolateral incisions
      is discussed in this case report with emphasis on mechanisms of this type of
      injury, surgical approach and management. 

PMID- 24889987
TI  - The effects of pediatric obesity on dynamic joint malalignment during gait.
AB  - BACKGROUND: There is a greater prevalence of lower extremity malalignment in
      obese children during static posture; however, there has been less examination of
      dynamic joint function in this cohort. Therefore, the purpose of this study was
      to determine kinematic differences that exist between obese and non-obese
      children that would support previously reported static joint malalignment.
      METHODS: Forty children were classified as obese (n=20) or non-obese (n=20).
      Lower extremity joint kinematics were collected during five walking trials at a
      self-selected pace. Peak joint displacement and amount of joint motion throughout
      the gait cycle (calculated as the integrated displacement curve) were analyzed
      for group differences. FINDINGS: Non-obese children had greater peak knee and hip
      extension during gait; however, there were no group differences in the integrated
      sagittal displacement curve. Obese children had greater peak angular displacement
      and integrals of angular displacement for peak hip adduction, hip internal
      rotation, and foot abduction (toe-out) than non-obese children. Obese children
      also had greater peak knee external rotation than non-obese children.
      INTERPRETATION: Non-obese children showed greater range of motion in the sagittal
      plane, particularly at the hip and knee. Frontal and transverse plane differences
      suggest that obese children function in a more genu valgum position than non
      obese children. Static measures of genu valgum have been previously associated
      with pediatric obesity; the findings indicate that there are also dynamic
      implications of said malalignment in obese children. Genu valgum presents
      increased risk of osteoarthritis for obese children and should be considered when
      prescribing weight bearing exercise to this cohort.

PMID- 24889988
TI  - Advances in asymmetric borrowing hydrogen catalysis.

PMID- 24889989
TI  - Spatial correlation in Bayesian logistic regression with misclassification.
AB  - Standard logistic regression assumes that the outcome is measured perfectly. In
      practice, this is often not the case, which could lead to biased estimates if not
      accounted for. This study presents Bayesian logistic regression with adjustment
      for misclassification of the outcome applied to data with spatial correlation.
      The models assessed include a fixed effects model, an independent random effects
      model, and models with spatially correlated random effects modelled using
      conditional autoregressive prior distributions (ICAR and ICAR(rho)). Performance
      of these models was evaluated in a simulation study. Parameters were estimated by
      Markov Chain Monte Carlo methods, using slice sampling to improve convergence.
      The results demonstrated that adjustment for misclassification must be included
      to produce unbiased regression estimates. With strong correlation the ICAR model
      performed best. With weak or moderate correlation the ICAR(rho) performed best.
      With unknown spatial correlation the recommended model would be the ICAR(rho),
      assuming convergence can be obtained.

PMID- 24889990
TI  - Spatial patterns of human papillomavirus-associated cancers within the state of
      Minnesota, 1998-2007.
AB  - Human papillomavirus (HPV) infection in women is a concern because it is
      considered a necessary cause of cervical cancer. Male HPV infection is also an
      important concern, both for the HPV-associated cancer burden in men and for the
      risk of transmission to women. Effective screening programs have greatly reduced
      cervical cancer incidence and mortality. HPV vaccines are expected to further
      reduce the burden of cervical cancer and other HPV-related cancers. However,
      disparities in terms of screening and HPV vaccination exist across the United
      States. In order to accurately identify areas of disparity, the spatial
      distributions of HPV-associated cancers has to be determined. To date, the
      geographic distribution and pattern exhibited by all HPV-associated cancers that
      accounts for spatial dependence have not been analyzed at a local level (i.e.
      county or ZIP code). This study analyzed the spatial dependence and pattern of
      HPV-associated cancers in Minnesota from 1998 to 2007 using sparse spatial
      generalized linear mixed models and scan statistics for cluster detection. A
      strong clustering pattern was seen in the northern region of Minnesota for both
      men and women. Separate cluster analyses by gender identified areas of
      overlapping disease burden. The patterns observed in this analysis demonstrate
      the need to account for spatial dependence when analyzing disease rates for
      geographic areas (i.e. county or ZIP codes) since spatial analyses of HPV
      associated cancers have the potential to identify areas with the highest HPV
      disease burden and may serve to uncover areas where policies and HPV vaccination
      strategies can be most beneficial.

PMID- 24889991
TI  - A space-time point process model for analyzing and predicting case patterns of
      diarrheal disease in northwestern Ecuador.
AB  - We consider modeling case-patterns under a complex spatial and longitudinal
      sampling design as conducted via a serial case-control study of diarrheal disease
      in northwestern Ecuador. We build a two-stage space-time model to understand the
      role of spatially and temporally referenced covariates that reflect social and
      natural environments in the sampled region, after accounting for unmeasured
      residual heterogeneities. All diarrheal case events are collected from 21 sampled
      communities in Esmeraldes province in Ecuador, during seven sampling cycles from
      2003 to 2008. The region of interest comprises 158 communities along a river
      basin. Prediction of case counts at unsampled communities at a future time is of
      interest along with estimation of risk-related parameters. We propose a
      computationally feasible two-stage Bayesian approach to estimate the risk-related
      parameters and conduct predictive inference. We first apply the log Gaussian Cox
      process (LGCP), commonly used to model spatial clustering of point patterns, to
      accommodate temporal variation within the sampled communities. Prediction of the
      number of cases at unsampled communities at a future time is obtained by a
      disease mapping model conditional on the expected case counts from Stage I.

PMID- 24889992
TI  - A comparison between self-reported and GIS-based proxies of residential exposure
      to environmental pollution in a case-control study on lung cancer.
AB  - In epidemiological studies both questionnaire results and GIS modeling have been
      used to assess exposure to environmental risk factors. Nevertheless, few studies
      have used both these techniques to evaluate the degree of agreement between
      different exposure assessment methodologies. As part of a case-control study on
      lung cancer, we present a comparison between self-reported and GIS-derived
      proxies of residential exposure to environmental pollution. 649 subjects were
      asked to fill out a questionnaire and give information about residential history
      and perceived exposure. Using GIS, for each residence we evaluated land use
      patterns, proximity to major roads and exposure to industrial pollution. We then
      compared the GIS exposure-index values among groups created on the basis of
      questionnaire responses. Our results showed a relatively high agreement between
      the two methods. Although none of these methods is the "exposure gold standard",
      understanding similarities, weaknesses and strengths of each method is essential
      to strengthen epidemiological evidence.

PMID- 24889993
TI  - Tunable elastic modulus of nanoparticle monolayer films by host-guest chemistry.
AB  - The elastic modulus of an ultrathin nanoparticle (NP) monolayer film is tuned by
      modulating the binding strength between the NPs on a molecular level. NP
      monolayer films constructed by crosslinking NPs of different binding affinities
      are fabricated at oil/water interfaces. By inducing buckling patterns on these
      films, the correlation between the binding affinity of the NPs and the elastic
      modulus is investigated. 

PMID- 24889994
TI  - Reexamining our bias against heuristics.
AB  - Using heuristics offers several cognitive advantages, such as increased speed and
      reduced effort when making decisions, in addition to allowing us to make decision
      in situations where missing data do not allow for formal reasoning. But the
      traditional view of heuristics is that they trade accuracy for efficiency. Here
      the authors discuss sources of bias in the literature implicating the use of
      heuristics in diagnostic error and highlight the fact that there are also data
      suggesting that under certain circumstances using heuristics may lead to better
      decisions that formal analysis. They suggest that diagnostic error is frequently
      misattributed to the use of heuristics and propose an alternative view whereby
      content knowledge is the root cause of diagnostic performance and heuristics lie
      on the causal pathway between knowledge and diagnostic error or success. 

PMID- 24889995
TI  - MR imaging of myxofibrosarcoma and undifferentiated sarcoma with emphasis on tail
      sign; diagnostic and prognostic value.
AB  - OBJECTIVES: To assess the prevalence of the tail sign in soft tissue sarcomas and
      determine whether the local recurrence rate differed based on the presence of the
      tail sign. METHODS: In our retrospective study, myxofibrosarcoma (MFS, n = 25)
      and undifferentiated sarcoma (US, n = 38) comprised group 1, and the remaining
      tumours (n = 115) were assigned to group 2. Location, size, and imaging features
      of the tumours were assessed on MRI. The radiological-pathological correlation of
      the tail sign was analysed. RESULTS: The tail sign, thick fascial enhancement
      extending from the tumour margin, was more common and significantly thicker in
      group 1. In the subgroup analysis between MFS and US, there was no significant
      difference in the presence of a tail sign. Histological examination revealed
      extensive tumour cell infiltrations along the deep fascia from the main mass.
      Patients with a tail sign had a worse local recurrence-free survival than
      patients without it, not only in all tumours (p < 0.01), but also in group 1 (p =
      0.019) CONCLUSIONS: The tail sign was a common MRI feature of both MFS and US,
      and was also associated with worse local recurrence-free survival. Radiologists
      should be aware of these MRI findings and inform the surgeon preoperatively in
      order to obtain a sufficient surgical margin to minimise the risk of local tumour
      recurrence. KEY POINTS: * The tail sign was a common MRI feature of
      myxofibrosarcoma and undifferentiated sarcoma. * The tail sign may be associated
      with worse local recurrence-free survival * Radiologists should be aware of this
      MRI finding and inform the surgeon.

PMID- 24889996
TI  - The impact of CT radiation dose reduction and iterative reconstruction algorithms
      from four different vendors on coronary calcium scoring.
AB  - OBJECTIVES: To analyse the effects of radiation dose reduction and iterative
      reconstruction (IR) algorithms on coronary calcium scoring (CCS). METHODS:
      Fifteen ex vivo human hearts were examined in an anthropomorphic chest phantom
      using computed tomography (CT) systems from four vendors and examined at four
      dose levels using unenhanced prospectively ECG-triggered protocols. Tube voltage
      was 120 kV and tube current differed between protocols. CT data were
      reconstructed with filtered back projection (FBP) and reduced dose CT data with
      IR. CCS was quantified with Agatston scores, calcification mass and calcification
      volume. Differences were analysed with the Friedman test. RESULTS: Fourteen
      hearts showed coronary calcifications. Dose reduction with FBP did not
      significantly change Agatston scores, calcification volumes and calcification
      masses (P > 0.05). Maximum differences in Agatston scores were 76, 26, 51 and 161
      units, in calcification volume 97, 27, 42 and 162 mm(3), and in calcification
      mass 23, 23, 20 and 48 mg, respectively. IR resulted in a trend towards lower
      Agatston scores and calcification volumes with significant differences for one
      vendor (P < 0.05). Median relative differences between reference FBP and reduced
      dose IR for Agatston scores remained within 2.0-4.6%, 1.0-5.3%, 1.2-7.7% and 2.6
      4.5%, for calcification volumes within 2.4-3.9%, 1.0-5.6%, 1.1-6.4% and 3.7-4.7%,
      for calcification masses within 1.9-4.1%, 0.9-7.8%, 2.9-4.7% and 2.5-3.9%,
      respectively. IR resulted in increased, decreased or similar calcification
      masses. CONCLUSIONS: CCS derived from standard FBP acquisitions was not affected
      by radiation dose reductions up to 80%. IR resulted in a trend towards lower
      Agatston scores and calcification volumes. KEY POINTS: In this ex vivo study,
      radiation dose could be reduced by 80% for coronary calcium scoring. Iterative
      reconstruction resulted in a trend towards lower Agatston scores and
      calcification volumes. Caution should be taken for coronary calcium scoring with
      iterative reconstruction.

PMID- 24889997
TI  - Preoperative lymph node staging in patients with primary prostate cancer:
      comparison and correlation of quantitative imaging parameters in diffusion
      weighted imaging and 11C-choline PET/CT.
AB  - PURPOSE: To compare the diagnostic performance of DWI and 11C-choline PET/CT in
      the assessment of preoperative lymph node status in patients with primary
      prostate cancer. MATERIAL AND METHODS: Thirty-three patients underwent DWI and
      11C-choline PET/CT prior to prostatectomy and extended pelvic lymph node
      dissection. Mean standardised uptake value (SUV(mean)) and mean apparent
      diffusion coefficient (ADC) of 76 identified lymph nodes (LN) were measured and
      correlated with histopathology. ADC values and SUVs were compared using linear
      regression analysis. RESULTS: A significant difference between benign and
      malignant LN was observed for ADC values (1.17 vs. 0.96 * 10(-3) mm(2)/s; P <
      0.001) and SUV(mean) (1.61 vs. 3.20; P < 0.001). ROC analysis revealed an optimal
      ADC threshold of 1.01 * 10(-3) mm(2)/s for differentiating benign from malignant
      LN with corresponding sensitivity/specificity of 69.70%/78.57% and an area under
      the curve (AUC) of 0.785. The optimal threshold for SUV(mean) was 2.5 with
      corresponding sensitivity/specificity of 69.72%/90.48% and with an AUC of 0.832.
      ADC values and SUV(mean) showed a moderate significant inverse correlation (r = 
      0.63). CONCLUSION: Both modalities reveal similar moderate diagnostic performance
      for preoperative lymph node staging of prostate cancer, not justifying their
      application in routine clinical practice at this time. The only moderate inverse
      correlation between ADC values and SUV(mean) suggests that both imaging
      parameters might provide complementary information on tumour biology. KEY POINTS:
      * Conventional imaging shows low performance for lymph node staging in prostate
      cancer. * DWI and 11C-choline PET/CT both provide additional functional
      information * Both functional modalities reveal only moderate diagnostic
      performance.

PMID- 24889998
TI  - Long-term results of preventive embolization of renal angiomyolipomas: evaluation
      of predictive factors of volume decrease.
AB  - OBJECTIVES: To evaluate the efficacy of selective arterial embolization (SAE) of
      angiomyolipomas based on the percentage volume reduction after embolization and
      to identify predictive factors of volume decrease. METHODS: Patients receiving
      prophylactic SAE of renal angiomyolipomas were included retrospectively over 3
      years. The volume change after SAE and haemorrhagic or surgical events were
      recorded. Initial tumour volume, percentage tumour fat content, mean tumour
      density, embolic agent used, number of angiomyolipomas and tuberous sclerosis
      disease were evaluated as predictive factors of volume decrease. RESULTS: A total
      of 19 patients with 39 angiomyolipomas were included with median follow-up of 28
      months (interquartile range 21-37 months). All treatments were technically
      successful (92% primary and 8% secondary). No distal bleeding or any increase in
      size or surgical nephrectomy after SAE was recorded. Mean volume reduction was
      72% (+/-24%). Volumes before SAE (R(2) = 0.276; p = 0.001), percentage fat
      content (R(2) = 0.612; p < 0.0001) and mean angiomyolipoma density (R(2) = 0.536;
      p < 0.0001) were identified as predictive factors of volume decrease. In
      multivariate regression, only percentage fat content influenced volume decreases.
      CONCLUSIONS: SAE is an efficient treatment for angiomyolipoma devascularisation
      and volume reduction. A significant reduction of volume is modulated by the
      initial volume and tissue composition of the tumour. KEY POINTS: * Selective
      arterial embolization is effective for angiomyolipoma devascularisation and
      volume reduction * Volume reduction depends of initial volume and tissue
      composition of the tumour * Selective arterial embolization is a low radiation
      treatment.

PMID- 24890000
TI  - Antidepressant adherence and risk of coronary artery disease hospitalizations in
      older and younger adults with depression.
AB  - OBJECTIVES: To assess whether the relationship between antidepressant adherence
      and coronary artery disease (CAD) hospitalizations varied between older and
      younger adults with depression. DESIGN: Retrospective cohort study. SETTING:
      Department of Veterans Affairs outpatient clinics nationwide. PARTICIPANTS:
      Chronically depressed individuals (n = 50,261; aged 20-97) who had been
      prescribed an antidepressant were identified from records indicating an
      outpatient clinic visit for depression (index depression visit) during fiscal
      years 2009 and 2010. Individuals were considered chronically depressed if they
      had had prior depression visits and treatment for depression within the previous
      4 months. The sample was age-stratified into younger (<65) and older (>= 65)
      groups. MEASUREMENTS: After the index depression visit, medication possession
      ratios were calculated from pharmacy refill data to determine whether
      participants had 80% or greater adherence to antidepressant refills during a 6
      month treatment observation period. International Classification of Diseases,
      Ninth Revision, codes were used to derive CAD-related hospitalizations during the
      follow-up period. Mean follow-up was 24 months. Data were analyzed using Cox
      proportional hazard models. RESULTS: Older participants with 80% or greater
      antidepressant adherence had 26% lower risk of CAD hospitalizations (hazard ratio
      = 0.74, 95% confidence interval = 0.60-0.93). Antidepressant adherence was not
      significantly related to CAD hospitalizations in younger adults. CONCLUSION:
      Older adults with chronic depression with 80% or greater antidepressant adherence
      had significantly lower risk of CAD hospitalizations at follow-up than those with
      less than 80% adherence. These preliminary results suggest that older adults with
      depression may derive cardiovascular benefits from clinical efforts to increase
      antidepressant adherence.

PMID- 24889999
TI  - Brain region's relative proximity as marker for Alzheimer's disease based on
      structural MRI.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive, incurable
      neurodegenerative disease and the most common type of dementia. It cannot be
      prevented, cured or drastically slowed, even though AD research has increased in
      the past 5-10 years. Instead of focusing on the brain volume or on the single
      brain structures like hippocampus, this paper investigates the relationship and
      proximity between regions in the brain and uses this information as a novel way
      of classifying normal control (NC), mild cognitive impaired (MCI), and AD
      subjects. METHODS: A longitudinal cohort of 528 subjects (170 NC, 240 MCI, and
      114 AD) from ADNI at baseline and month 12 was studied. We investigated a marker
      based on Procrustes aligned center of masses and the percentile surface
      connectivity between regions. These markers were classified using a linear
      discriminant analysis in a cross validation setting and compared to whole brain
      and hippocampus volume. RESULTS: We found that both our markers was able to
      significantly classify the subjects. The surface connectivity marker showed the
      best results with an area under the curve (AUC) at 0.877 (p<0.001), 0.784
      (p<0.001), 0,766 (p<0.001) for NC-AD, NC-MCI, and MCI-AD, respectively, for the
      functional regions in the brain. The surface connectivity marker was able to
      classify MCI-converters with an AUC of 0.599 (p<0.05) for the 1-year period.
      CONCLUSION: Our results show that our relative proximity markers include more
      information than whole brain and hippocampus volume. Our results demonstrate that
      our proximity markers have the potential to assist in early diagnosis of AD.

PMID- 24890001
TI  - Surgery-induced changes in rat IL-1beta and acetylcholine metabolism: role of
      physostigmine.
AB  - Pharmacological enhancement of cholinergic activity following administration of
      physostigmine is known to induce protective effects generally. However, it is
      unclear whether the effect of physostigmine on inflammation and acetylcholine
      (ACh) metabolism is related to different types of surgical intervention or
      anaesthesia alone. To investigate this, rats were subjected to partial liver
      resection (PLR) or sham surgery, with a control group receiving anaesthesia
      alone. Half of each treatment group received a single intra-operative dose of
      physostigmine (0.04 mg/kg); the others received placebo. Acetylcholinesterase
      (AChE) activity and plasma and brain concentrations of interleukin (IL)-1beta and
      ACh were determined. Both PLR and sham operation induced a time-dependent
      increase in plasma concentrations of IL-1beta compared with rats receiving
      anaesthesia alone (3.9- and 4.8-fold increases, respectively). In the brain, IL
      1beta concentrations had increased approximately twofold after surgery compared
      with the control group. Blood AChE was transiently decreased after surgery. Brain
      AChE activity increased 1.3-fold (P = 0.014) only after PLR; consequently,
      cerebral ACh concentrations were significantly reduced. Physostigmine
      administration significantly reduced IL-1beta and AChE levels. Cerebral ACh
      concentrations were markedly increased from 544 +/- 122 ng/mg protein following
      placebo administration to 654 +/- 93 ng/mg protein after physostigmine
      administrations (P < 0.001). We conclude that a single dose of physostigmine
      intra-operatively has a sustained anti-inflammatory effect (up to 120 min after
      injection) that is especially pronounced under the conditions of PLR surgery. In
      addition to its protective peripheral action, physostigmine exerts a
      neuroprotective action by increasing levels of the neurotransmitter ACh. 

PMID- 24890007
TI  - Speech evoked auditory brainstem response findings in children with epilepsy.
AB  - OBJECTIVES: Children with epilepsy are at a considerable risk of cognitive
      impairment and school failure. Previous studies have typically documented
      abnormal responses in children with epilepsy at cortical level using speech
      stimuli. Recent studies reported that abnormal neural encoding of a speech
      syllable could be detected at the level of the brainstem using speech-evoked
      auditory brainstem response (ABR). The aim of this study is to investigate speech
      evoked (ABR) results in children with epilepsy. METHODS: The study group
      consisted of 38 recently diagnosed epileptic children; none of them has received
      antiepileptic therapy. They were 22 males and 16 females with age 9.1 +/- 3.1
      years. The control group consisted of 38 healthy normal hearing children with
      matched age and gender distribution. All subjects underwent full history taking,
      basic audiologic evaluation including pure-tone, speech audiometry and immittance
      testing. Click ABR response was recorded monaurally from both ears at 90 dB nHL
      then speech ABR was recorded monaurally from each ear at 80 dB SPL. RESULTS:
      Though the study group disclosed normal click ABR compared to age matched
      normative values, speech-evoked ABR revealed a delayed waves V and A latencies in
      both ears. These findings reflect abnormal neural encoding of speech at the level
      of brainstem. The younger the age of epileptic child the more prolonged wave A
      latency and increased V/A inter-latency values. CONCLUSIONS: Speech-evoked ABR
      results denote abnormal timing in the brainstem; such brainstem abnormality could
      be detected by speech evoked ABR rather than conventional click evoked ABR.

PMID- 24890009
TI  - Selective functionalization of P4 by metal-mediated C-P bond formation.
AB  - A new and selective one-step synthesis was developed for the first activation
      stage of white phosphorus by organic radicals. The reactions of NaCp(R) with P4
      in the presence of CuX or FeBr3 leads to the clean formation of organic
      substituted P4 butterfly compounds Cp(R)2P4 (Cp(R): Cp(BIG)=C5(4-nBuC6H4)5 (1 a),
      Cp'''=C5H2tBu3 (1 b), Cp*=C5Me5 (1 c) und Cp(4iPr)=C5HiPr4 (1 d)). The reaction
      proceeds via the activation of P4 by Cp(R) radicals mediated by transition
      metals. The newly formed organic derivatives of P4 have been comprehensively
      characterized by NMR spectroscopy and X-ray crystallography.

PMID- 24890010
TI  - Rich conscious perception outside focal attention.
AB  - Can we consciously see more items at once than can be held in visual working
      memory? This question has eluded resolution because the ultimate evidence is
      subjects' reports in which phenomenal consciousness is filtered through working
      memory. However, a new technique makes use of the fact that unattended 'ensemble
      properties' can be detected 'for free' without decreasing working memory
      capacity. 

PMID- 24890008
TI  - Anti-inflammatory and anti-apoptotic effect of combined treatment with
      methylprednisolone and amniotic membrane mesenchymal stem cells after spinal cord
      injury in rats.
AB  - This study was undertaken to investigate the synergistic effects of
      methylprednisolone (MP) administration and transplantation of amniotic membrane
      mesenchymal stem cells (AM-MSCs) following T11 spinal cord clip compressive
      injury in rats. The combination treatment with MP (50 mg/kg) and delayed
      transplantation of AM-MSCs after rat spinal cord injury, significantly reduced
      (1) myeloperoxidase activity, (2) the proinflammatory cytokines: tumor necrosis
      factor-alpha, interleukin (IL)-1beta, IL-6, IL-17, interferon-gamma and (3) the
      cell apoptosis [terminal deoxynucleotidyl transferase, dUTP nick end labeling
      (TUNEL) staining, and caspase-3, Bax and Bcl-2 expressions]; increased: (1) the
      levels of the anti-inflammatory cytokines (IL-10 and transforming growth factor
      beta1) and (2) the survival rate of AM-MSCs in the injury site. The combination
      therapy significantly ameliorated the recovery of limb function (evaluated by
      Basso, Beattie and Bresnahan score). Taken together, our results demonstrate that
      MP in combination with AM-MSCs transplantation is a potential strategy for
      reducing secondary damage and promoting functional recovery following spinal cord
      injury. 

PMID- 24890011
TI  - Next-generation approaches to advancing eco-immunogenomic research in critically
      endangered primates.
AB  - High-throughput sequencing platforms are generating massive amounts of genomic
      data from nonmodel species, and these data sets are valuable resources that can
      be mined to advance a number of research areas. An example is the growing amount
      of transcriptome data that allow for examination of gene expression in nonmodel
      species. Here, we show how publicly available transcriptome data from nonmodel
      primates can be used to design novel research focused on immunogenomics. We mined
      transcriptome data from the world's most endangered group of primates, the lemurs
      of Madagascar, for sequences corresponding to immunoglobulins. Our results
      confirmed homology between strepsirrhine and haplorrhine primate immunoglobulins
      and allowed for high-throughput sequencing of expressed antibodies (Ig-seq) in
      Coquerel's sifaka (Propithecus coquereli). Using both Pacific Biosciences RS and
      Ion Torrent PGM sequencing, we performed Ig-seq on two individuals of Coquerel's
      sifaka. We generated over 150 000 sequences of expressed antibodies, allowing for
      molecular characterization of the antigen-binding region. Our analyses suggest
      that similar VDJ expression patterns exist across all primates, with sequences
      closely related to the human VH 3 immunoglobulin family being heavily represented
      in sifaka antibodies. Moreover, the antigen-binding region of sifaka antibodies
      exhibited similar amino acid variation with respect to haplorrhine primates. Our
      study represents the first attempt to characterize sequence diversity of the
      expressed antibody repertoire in a species of lemur. We anticipate that methods
      similar to ours will provide the framework for investigating the adaptive immune
      response in wild populations of other nonmodel organisms and can be used to
      advance the burgeoning field of eco-immunology.

PMID- 24890012
TI  - Fibroblast growth factor-21: a metabolic regulator or something more?

PMID- 24890013
TI  - Genetic predisposition scores for dyslipidaemia influence plasma lipid
      concentrations at baseline, but not the changes after controlled intake of n-3
      polyunsaturated fatty acids.
AB  - Inconsistent effects of fish oil supplementation on plasma lipids may be
      influenced by genetic variation. We investigated 12 single nucleotide
      polymorphisms (SNPs) associated with dyslipidaemia in genome-wide association
      studies, in 310 participants randomised to treatment with placebo or 0.45, 0.9
      and 1.8 g/day eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid
      (22:6n-3, DHA) (1.51:1) in a 12-month parallel controlled trial. Effects of risk
      alleles were assessed as trait-specific genetic predisposition scores (GPS) and
      singly. GPS were positively associated with baseline concentrations of plasma
      total cholesterol, low-density-lipoprotein cholesterol and triglyceride (TG) and
      negatively with high-density-lipoprotein cholesterol. The TG-GPS was associated
      with 0.210 mmol/L higher TG per risk allele (P < 0.0001), but no effects of
      single TG SNPs were significant at baseline. After treatment with EPA and DHA, TG
      GPS was associated with 0.023 mmol/L lower TG per risk allele (P = 0.72). No
      interactions between GPS and treatment were significant; however, FADS1 SNP
      rs174546 C/T interaction with treatment was a significant determinant of plasma
      TG concentration (P = 0.047, n = 267). Concentration differed between genotype
      groups after the 1.8 g/day dose (P = 0.026), decreasing by 3.5 (95 % CI -15.1 to
      8.2) % in non-carriers of the risk T-allele (n = 30) and by 21.6 (95 % CI -32.1
      to -11.2) % in carriers (n = 37), who showed a highly significant difference
      between treatments (P = 0.007). Carriers of the FADS1 rs174546 risk allele could
      benefit from a high intake of EPA and DHA in normalising plasma TG. 

PMID- 24890015
TI  - Normal nerve striations are altered in the trembler-J mouse, a model of Charcot
      Marie-Tooth disease.
AB  - INTRODUCTION: This study was initiated because it was noted that the peripheral
      nerves of Trembler-J mice (a model of human Charcot-Marie-Tooth disease) appear
      to lack normal striations. METHODS: We performed confocal microscopy of whole
      sciatic nerves and tested the effect of axial stress on impulse conduction.
      RESULTS: We found that the axons of mutant mice were longer than those of the
      wild-type (1.55 mm of axon/mm length of nerve vs. 1.28 mm/mm respectively). This
      axonal elongation altered the helical nerve striations (bands of Fontana). As
      nerves were stretched axially, the conduction distance became correspondingly
      shorter. The effect on latency was significantly greater in the more coiled
      nerves of Trembler-J mice (P = 0.038). CONCLUSIONS: The finding that mice with a
      mutated peripheral myelin protein 22 (PMP22) possess excessively long axons may
      be related to the excess Schwann cell numbers found in this disorder.

PMID- 24890014
TI  - Controlled rehabilitative and supportive care intervention trials in patients
      with high-grade gliomas and their caregivers: a systematic review.
AB  - BACKGROUND: Patients diagnosed with high-grade gliomas experience a varying and
      complex symptom burden, and face a high mortality rate. As a consequence,
      patients with high-grade gliomas and their caregivers have imminent and changing
      rehabilitative and supportive care needs. OBJECTIVES: To give a detailed overview
      of non-pharmacological rehabilitative and supportive care interventions for
      patients with high-grade gliomas and/or their caregivers, and provide an
      appraisal of the methodological quality of these studies. METHOD: PubMed,
      Cumulative Index of Nursing and Allied Health Literature and Embase were searched
      for literature published from 1995 to May 2013. Data from eight studies were
      reviewed for substantive methods and results. Methodological quality was
      described and assessed using the scoring system for appraising mixed methods
      research and concomitantly appraising qualitative, quantitative and mixed methods
      primary studies in mixed study reviews. RESULTS: The search yielded 914 unique
      publications, of which 9 were classified eligible for this review. There is
      preliminary evidence that cognitive group therapy improves memory skills in
      patients with high-grade gliomas, early physical training improves functional
      outcome and massage therapy reduces stress. Patients and caregivers found that
      telephone follow-up and a specialist nurse function was an effective and useful
      way to achieve information and support. Finally, psycho-education increased
      feelings of mastery among caregivers. CONCLUSIONS: As evidence is beginning to
      emerge, there is a need for well-designed longitudinal and randomised controlled
      trials of non-pharmacological interventions in high-grade glioma patients and
      their caregivers in order to develop clinical guidelines for supportive and
      rehabilitative approaches in this unique population.

PMID- 24890016
TI  - Effects of diallyl trisulfide on induction of apoptotic death in murine leukemia
      WEHI-3 cells in vitro and alterations of the immune responses in normal and
      leukemic mice in vivo.
AB  - Diallyl trisulfide (DATS), a chemopreventive dietary constituent and extracted
      from garlic, has been shown to against cultured many types of human cancer cell
      liens but the fate of apoptosis in murine leukemia cells in vitro and immune
      responses in leukemic mice remain elusive. Herein, we clarified the actions of
      DATS on growth inhibition of murine leukemia WEHI-3 cells in vitro and used WEHI
      3 cells to generate leukemic mice in vivo, following to investigate the effects
      of DATS in animal model. In in vitro study, DATS induced apoptosis of WEHI-3
      cells through the G0/G1 phase arrest and induction of caspase-3 activation. In in
      vivo study DATS decreased the weight of spleen of leukemia mice but did not
      affect the spleen weight of normal mice. DATS promoted the immune responses such
      as promotions of the macrophage phagocytosis and NK cell activities in WEHI-3
      leukemic and normal mice. However, DATS only promotes NK cell activities in
      normal mice. DATS increases the surface markers of CD11b and Mac-3 in leukemia
      mice but only promoted CD3 in normal mice. In conclusion, the present study
      indicates that DATS induces cell death through induction of apoptosis in mice
      leukemia WHEI-3 cells. DATS also promotes immune responses in leukemia and normal
      mice in vivo.

PMID- 24890020
TI  - Efficiency enhancement in Cu2ZnSnS4 solar cells with subwavelength grating
      nanostructures.
AB  - In the article, a study of sub-wavelength grating (SWG) nanostructures for
      broadband and omni-directional anti-reflection coatings (ARCs) on Cu2ZnSnS4
      (CZTS) solar cells using the rigorous coupled-wave analysis (RCWA) method is
      presented. Various SWG nanostructures of different shapes and periodic geometry
      on CZTS solar cells are discussed in detail. The optimized reflectance decreased
      to 1.67%, and efficiency increased to 13.74%, accordingly. The omni-directional
      and broadband antireflections of the SWG nanostructures are also investigated.
      Under a simulated 1-sun condition and with the light incident angle increased to
      80 degrees , cells with SWG nanostructures enhanced the short-circuit current
      density by 16.5%. This considerable enhancement in light harvesting is attributed
      to the linearly graded effective refractive index profile from the air to the
      device surface. 

PMID- 24890018
TI  - Development of a complete human anti-human transferrin receptor C antibody as a
      novel marker of oral dysplasia and oral cancer.
AB  - Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up
      to 20% of oral dysplasia cases have been suggested to undergo malignant
      transformation to OSCC; however, there are no methods to predict OSCC
      development. In this study, to identify the genes associated with oral dysplasia
      progression, we performed genomic copy number analyses of genomic DNA samples
      isolated from primary oral dysplasia and OSCC via the microdissection method and
      found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic
      amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was
      significantly higher than that in dysplasia, suggesting that OSCC disease
      progression might be related to TFRC expression. Additionally, we investigated
      the in vitro and in vivo impacts of a newly established anti-human TFRC
      monoclonal antibody, which was isolated from a human cDNA library using the phage
      display method, on cell proliferation and survival. The anti-TFRC antibody
      blocked the interaction between transferrin and TFRC and consequently inhibited
      iron uptake, leading to the iron deprivation-mediated suppression of cell growth
      and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody
      efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore,
      we suggest our developed complete human anti-human TFRC antibody as a useful,
      novel treatment for oral dysplasia and OSCC. 

PMID- 24890019
TI  - Design, synthesis, and antimicrobial evaluation of hexadentate hydroxypyridinones
      with high iron(III) affinity.
AB  - A range of hexadentate 3-hydroxypyridin-4-ones (HPOs) with high affinity for
      iron(III) has been synthesized. The log stability constants of two HPO-iron
      complexes (logK1 ) were determined to be over 34, and pFe values of the two HPOs
      were determined to be over 31. Antimicrobial assay indicated that they are able
      to markedly inhibit the growth of both Gram-positive and Gram-negative bacteria.
      Compounds 14a and 14e were found to exhibit the strongest inhibitory activity
      against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and
      Escherichia coli, with MIC values of 8, 8, 16, and 8 MUg/mL, respectively. These
      results indicate that hexadentate 3-hydroxypyridin-4-ones have potential
      application as antimicrobial agents, especially in the treatment of wound
      infection.

PMID- 24890021
TI  - Who can blame who for what and how in responsibility for health?
AB  - This paper starts by introducing a tripartite conception of responsibility for
      health consisting of a moral agent having moral responsibilities and being held
      responsible, that is blamed, for failing to meet them and proceeds to a brief
      discussion of the nature of the blame, noting difficulties in agency and
      obligation when the concept is applied to health-threatening behaviours. Insights
      about the obligations that we hold people to and the extent of their moral agency
      are revealed by interrogating our blaming behavior, and to facilitate this, my
      own blaming attitudes and actions are analysed in respect of an imagined adult
      son who seeks thrills by jumping from a pier into the sea, an activity common
      around coastlines and intended to be analogous in varying degrees to a range of
      health-threatening behaviours. I consider my responses to this imagined act in
      relation to some features of moralism, the excess of morality, concluding that
      blame can be justified when it is proportionate and within interpersonal
      relationships. There is evidence that some nurses hold negative blaming attitudes
      towards groups of patients considered to have caused or contributed to their
      illness, but this is not justified, not only because of impaired agency, but also
      because if there is responsibility for health, associated obligations are owed to
      those who share our lives, and it is those people who are entitled to hold
      individuals responsible. Nurses who hold negative blaming attitudes towards
      groups of patients are invited to identify the status of moral agency, the
      precise natures of their (failed) obligations, and of the patient-nurse
      relationship. It is concluded that reflection on these matters and the difference
      between justified blame and moralism demonstrates that blaming behaviour in the
      context of professional health care is built on nothing stronger than prejudice. 

PMID- 24890022
TI  - Secretome analysis of Anabaena sp. PCC 7120 and the involvement of the TolC
      homologue HgdD in protein secretion.
AB  - Secretion of proteins is a central strategy of bacteria to influence and respond
      to their environment. Until now, there has been very few discoveries regarding
      the cyanobacterial secrotome or the secretion machineries involved. For a mutant
      of the outer membrane channel TolC-homologue HgdD of Anabaena sp. PCC 7120, a
      filamentous and heterocyst-forming cyanobacterium, an altered secretome profile
      was reported. To define the role of HgdD in protein secretion, we have developed
      a method to isolate extracellular proteins of Anabaena sp. PCC 7120 wild type and
      an hgdD loss-of-function mutant. We identified 51 proteins of which the majority
      is predicted to have an extracellular secretion signal, while few seem to be
      localized in the periplasmic space. Eight proteins were exclusively identified in
      the secretome of wild-type cells, which coincides with the distribution of type I
      secretion signal. We selected three candidates and generated hemagglutinin-tagged
      fusion proteins which could be exclusively detected in the extracellular protein
      fraction. However, these proteins are not secreted in the hgdD-mutant background,
      where they are rapidly degraded. This confirms a direct function of HgdD in
      protein secretion and points to the existence of a quality control mechanism at
      least for proteins secreted in an HgdD-dependent pathway.

PMID- 24890023
TI  - Solar burn reactivation reaction: an unusual side effect of methotrexate.

PMID- 24890024
TI  - Leptospira species and serovars identified by MALDI-TOF mass spectrometry after
      database implementation.
AB  - BACKGROUND: Leptospirosis, a spirochaetal zoonotic disease of worldwide
      distribution, endemic in Europe, has been recognized as an important emerging
      infectious disease, though yet it is mostly a neglected disease which imparts its
      greatest burden on impoverished populations from developing countries.
      Leptospirosis is caused by the infection with any of the more than 230 serovars
      of pathogenic Leptospira sp. In this study we aimed to implement the MALDI-TOF
      mass spectrometry (MS) database currently available in our laboratory with
      Leptospira reference pathogenic (L. interrogans, L. borgpetersenii, L.
      kirschneri, L. noguchii), intermediate (L. fainei) and saprophytic (L. biflexa)
      strains of our collection in order to evaluate its possible application to the
      diagnosis of leptospirosis and to the typing of strains. This was done with the
      goal of understanding whether this methodology could be used as a tool for the
      identification of Leptospira strains, not only at species level for diagnostic
      purposes, but also at serovar level for epidemiological purposes, overcoming the
      limits of serological and molecular conventional methods. Twenty Leptospira
      reference strains were analysed by MALDI-TOF MS. Statistical analysis of the
      protein spectra was performed by ClinProTools software. RESULTS: The spectra
      obtained by the analysis of the reference strains tested were grouped into 6 main
      classes corresponding to the species analysed, highlighting species-specific
      protein profiles. Moreover, the statistical analysis of the spectra identified
      discriminatory peaks to recognize Leptospira strains also at serovar level
      extending previously published data. CONCLUSIONS: In conclusion, we confirmed
      that MALDI-TOF MS could be a powerful tool for research and diagnostic in the
      field of leptospirosis with broad applications ranging from the detection and
      identification of pathogenic leptospires for diagnostic purposes to the typing of
      pathogenic and non-pathogenic leptospires for epidemiological purposes in order
      to enrich our knowledge about the epidemiology of the infection in different
      areas and generate control strategies.

PMID- 24890025
TI  - A comparative study between para-aminophenyl and ortho-aminophenyl benzothiazoles
      using NMR and DFT calculations.
AB  - Ortho-substituted and para-substituted aminophenyl benzothiazoles were
      synthesised and characterised using NMR spectroscopy. A comparison of the proton
      chemical shift values reveals significant differences in the observed chemical
      shift values for the NH protons indicating the presence of a hydrogen bond in all
      ortho-substituted compounds as compared to the para compounds. The presence of
      intramolecular hydrogen bond in the ortho amino substituted aminophenyl
      benzothiazole forces the molecule to be planar which may be an additional
      advantage in developing these compounds as Alzheimer's imaging agent because the
      binding to amyloid fibrils prefers planar compounds. The splitting pattern of the
      methylene proton next to the amino group also showed significant coupling to the
      amino proton consistent with the notion of the existence of slow exchange and
      hydrogen bond in the ortho-substituted compounds. This is further verified by
      density functional theory calculations which yielded a near planar low energy
      conformer for all the o-aminophenyl benzothiazoles and displayed a hydrogen bond
      from the amine proton to the nitrogen of the thiazole ring. A detailed analysis
      of the (1)H, (13)C and (15)N NMR chemical shifts and density functional theory
      calculated structures of the compounds are described.

PMID- 24890026
TI  - The Dental Practice Questionnaire: a patient feedback tool for improving the
      quality of dental practices.
AB  - BACKGROUND: The recently introduced Practice Accreditation Scheme as part of the
      Australian National Safety and Quality Health Service (NSQHS) standards raises
      the question of how dental practices can implement valid and reliable patient
      experience feedback mechanisms for performance evaluation and enhancement. This
      article describes the development and use of a dental patient questionnaire (DPQ)
      that can be used for this purpose. METHODS: DPQ was piloted on 58 voluntary
      dental practices across Australia and resulted in an average of just over 50
      patient responses to 35 practices returned. Statistical properties of the DPQ
      were tested through validity (construct, content and criterion), structural
      integrity and reliability measurements. RESULTS: DPQ is valid and reliable, with
      statistical analysis showing that there are significant differences in patients'
      scores depending on their age, gender, regularity of visit and number of years
      attending the practice. Two patient satisfaction models were derived. However,
      there may be scope for improving DPQ to more effectively produce patient feedback
      on summative aspects of services provided by dental practices. CONCLUSIONS: DPQ
      has been shown to be 'fit for purpose' in its first pilot and may prove to be a
      useful tool for supporting dental practices in the Practice Accreditation Scheme.

PMID- 24890027
TI  - A broken heart.

PMID- 24890028
TI  - Tumor-infiltrating lymphocyte therapy for melanoma: rationale and issues for
      further clinical development.
AB  - Cancer immunotherapy has become an important area for the future development of
      cancer therapy; this includes T-cell-based therapies that involve adoptive
      transfer of autologous T cells derived from the tumors or peripheral blood of
      cancer patients, vaccines, oncolytic virus therapy, and immunomodulatory
      antibodies and ligands. Here, we summarize the current approaches and clinical
      data in the field of adoptive T-cell transfer therapy using tumor-infiltrating
      lymphocytes (TILs) for metastatic melanoma. We also discuss current knowledge on
      the mechanism of transferred TILs in mediating tumor regression and the growing
      need for and recent advances in the identification of predictive biomarkers to
      better select patients for TIL therapy. The current technical limitations of
      current TIL expansion methods for out-scaling are discussed as well as how these
      are being addressed in order to further "industrialize" this form of cell
      therapy. Lastly, how TIL adoptive transfer can be incorporated into the current
      melanoma treatment continuum, especially as combination therapy with other
      immunomodulators and targeted drugs, is discussed. 

PMID- 24890029
TI  - The role of interleukin-17A in psoriatic disease.
AB  - The pathogenic mechanisms of specific immune-mediated inflammatory diseases
      (IMIDs) are not fully understood, but are thought to involve activated T cells
      with the release of pro-inflammatory cytokines. Understanding the autoimmune
      inflammatory pathways has led to the development of biological agents that target
      specific components of effector immune mechanisms. Despite the availability of
      many effective drugs, a large proportion of patients with moderate to severe IMID
      do not receive adequate treatment, and many therapies show decreased efficacy
      over time. Therefore, there is a need for new therapies. One subset of T helper
      cells, Th17, and the cytokine interleukin-17 (IL-17) play a central role in the
      pathophysiology of autoimmune diseases such as psoriasis. IL-17 is involved in
      the modulation of pro-inflammatory cytokines, haematopoietic growth factors,
      antimicrobial peptides, chemokines, and molecules involved in tissue remodelling;
      the inflammatory cascades triggered by Th17 cells and IL-17 itself, when
      unregulated, can result in widespread inflammation-related damage. Evidence of
      increased Th17 activity and high levels of IL-17 has been found in psoriasis, as
      well as other inflammatory conditions, thereby signalling the potential utility
      of IL-17 as a therapeutic target. Clinical trials investigating IL-17 inhibitors,
      such as secukinumab, in patients with psoriatic disease have reported no
      significant safety concerns so far. It is hoped that these agents will improve
      the long-term prognosis of patients with these debilitating disorders. 

PMID- 24890030
TI  - Impact of source of infection and vancomycin AUC0-24/MICBMD targets on treatment
      failure in patients with methicillin-resistant Staphylococcus aureus bacteraemia.
AB  - Despite recent controversies about toxicity and reduced efficacy, vancomycin
      remains the current treatment of choice for methicillin-resistant Staphylococcus
      aureus (MRSA) bacteraemia. The parameter associated with treatment success is the
      vancomycin 24-h area under concentration-time curve to MIC ratio (AUC0-24/MIC).
      We aimed to determine the utility of calculated AUCs and explore the optimal AUC0
      24/MIC targets associated with treatment success. In this single-centre
      retrospective observational cohort study of 127 patients with MRSA bacteraemia,
      forty-five (35.4%) did not respond to vancomycin treatment. Patient
      characteristics were essentially the same between those who did not respond to
      vancomycin treatment and those with treatment success, with independent
      predictors of treatment failure being source of bacteraemia (odds ratio (OR),
      4.29; 95% confidence interval (CI), 1.50-12.26; p 0.007) and not achieving an
      AUC0-24/MICBMD (using broth microdilution) target of >=398 (OR, 11.4; 95% CI,
      4.57-28.46; p< 0.001). Bacteraemic source-specific thresholds were observed with
      a higher AUC0-24/MICBMD target of 440 required for high-risk sources (e.g.
      infective endocarditis) compared with 330 for low-risk sources (line related
      bacteraemia). Overall treatment success in patients with MRSA bacteraemia was
      associated with a vancomycin AUC0-24/MICBMD target of >=398, with source-specific
      targets observed. Future vancomycin practice guidelines will need to take into
      account MIC methodology, source of bacteraemia and patient populations prior to
      setting targets and monitoring recommendations.

PMID- 24890031
TI  - Nuchal translucency measurement plus non-invasive prenatal testing to screen for
      aneuploidy in a community-based average-risk population.

PMID- 24890033
TI  - Method to control depth error when ablating human dentin with numerically
      controlled picosecond laser: a preliminary study.
AB  - A three-axis numerically controlled picosecond laser was used to ablate dentin to
      investigate the quantitative relationships among the number of additive pulse
      layers in two-dimensional scans starting from the focal plane, step size along
      the normal of the focal plane (focal plane normal), and ablation depth error. A
      method to control the ablation depth error, suitable to control stepping along
      the focal plane normal, was preliminarily established. Twenty-four freshly
      removed mandibular first molars were cut transversely along the long axis of the
      crown and prepared as 48 tooth sample slices with approximately flat surfaces.
      Forty-two slices were used in the first section. The picosecond laser was 1,064
      nm in wavelength, 3 W in power, and 10 kHz in repetition frequency. For a varying
      number (n = 5-70) of focal plane additive pulse layers (14 groups, three
      repetitions each), two-dimensional scanning and ablation were performed on the
      dentin regions of the tooth sample slices, which were fixed on the focal plane.
      The ablation depth, d, was measured, and the quantitative function between n and
      d was established. Six slices were used in the second section. The function was
      used to calculate and set the timing of stepwise increments, and the single-step
      size along the focal plane normal was d micrometer after ablation of n layers (n
      = 5-50; 10 groups, six repetitions each). Each sample underwent three-dimensional
      scanning and ablation to produce 2 * 2-mm square cavities. The difference, e,
      between the measured cavity depth and theoretical value was calculated, along
      with the difference, e 1, between the measured average ablation depth of a single
      step along the focal plane normal and theoretical value. Values of n and d
      corresponding to the minimum values of e and e 1, respectively, were obtained. In
      two-dimensional ablation, d was largest (720.61 MUm) when n = 65 and smallest
      when n = 5 (45.00 MUm). Linear regression yielded the quantitative relationship:
      d = 10.547 * n - 7.5465 (R (2) = 0.9796). During three-dimensional ablation, e 1
      was the smallest (0.02 MUm) when n = 5 and d = 45.00 MUm. The depth error was
      1.91 MUm when 450.00-MUm depth cavities were produced. When ablating dentin with
      a three-axis picosecond laser scan-ablation device (450 MUm, 3 W, 10 kHz), the
      number of focal plane additive pulse layers and step size along the focal plane
      normal was positively correlated with the single-layer and total ablation depth
      errors. By adjusting the timing of stepwise increments along the focal plane
      normal and single-step size when ablating dentin by using the numerically
      controlled picosecond laser, the single-step ablation depth error could be
      controlled at the micrometer level. 

PMID- 24890032
TI  - Is sodium valproate, an HDAC inhibitor, associated with reduced risk of stroke
      and myocardial infarction? A nested case-control study.
AB  - BACKGROUND: This study aimed to evaluate whether treatment with sodium valproate
      (SV) was associated with reduced risk of stroke or myocardial infarction (MI).
      METHODS: Electronic health records data were extracted from Clinical Practice
      Research Database for participants ever diagnosed with epilepsy and prescribed
      antiepileptic drugs. A nested case-control study was implemented with cases
      diagnosed with incident non-haemorrhagic stroke and controls matched for sex,
      year of birth, and study start date (ratio of 1:6). A second nested study was
      implemented with MI as outcome. The main exposure variable was SV therapy
      assessed as: ever prescribed, pre-stroke year treatment, number of SV
      prescriptions, and cumulative time on SV drug therapy. Odds ratios were estimated
      using conditional logistic regression. RESULTS: Data were analysed for 2002
      stroke cases and 13,098 controls. MI analyses included 1153 cases and 7109
      controls. Pre-year stroke SV treatment (28%) was associated with increased stroke
      risk (odds ratio 1.22, 95% confidence interval (CI): 1.09 to 1.38, p < 0.001). No
      association was observed between ever being prescribed SV with ischemic stroke
      (OR = 1.01, 95% CI: 0.91 to 1.12, p = 0.875). A significant association was
      observed between ever being prescribed SV with MI (OR = 0.78, 95% CI: 0.67 to
      0.90, p < 0.001). Patients in the highest quarter of SV treatment duration had
      lower odds of ischemic stroke (OR = 0.57, 95% CI: 0.44 to 0.72, p < 0.001) and MI
      (OR = 0.29, 95% CI: 0.20 to 0.44, p < 0.001). CONCLUSION: Sodium valproate
      exposure was associated with the risk of MI, but not ischemic stroke. However,
      longer exposure to SV was associated with lower odds of stroke, but this might be
      explained by survivor bias.

PMID- 24890035
TI  - Controversy regarding the association of high calcium intake and increased risk
      for cardiovascular disease.
AB  - Calcium intake has been shown to be associated with beneficial effects regarding
      hypertension, coronary heart disease (CHD), vascular disease, and stroke by
      several prospective cohort studies. However, recent studies have questioned the
      beneficial cardiovascular effects of calcium intake and instead have shown that
      high calcium intake is associated with an increased risk for CHD and stroke.
      These findings have created controversy and concern among physicians, because
      calcium is consumed by a large number of older men and women to prevent
      osteoporosis and bone fractures. Based on the methods of patient self-reporting
      of calcium intake and cardiovascular events, the conclusions drawn from the
      studies may not be entirely valid. Therefore, until more confirmatory data are
      available, physicians should not be dissuaded from prescribing calcium
      supplements to their patients. The best candidates are patients with low calcium
      intake, but their calcium supplementation should not exceed the recommended 1200
      mg/d to 1500 mg/d.

PMID- 24890034
TI  - Effects of low-level laser therapy on joint pain, synovitis, anabolic, and
      catabolic factors in a progressive osteoarthritis rabbit model.
AB  - The aim of this study was to investigate the effect of low-level laser therapy
      (LLLT) on short-term and long-term joint pain, synovitis, anabolic, and catabolic
      factors in the cartilage of a rabbit model with progressive osteoarthritis (OA)
      induced by anterior cruciate ligament transection (ACLT). A total of 160 New
      Zealand white rabbits were randomly assigned into two groups (ACLT group and LLLT
      group). All rabbits received ACLT surgery, and 2-, 4-, 6-, and 8-week treatment
      after the surgery, with 20 rabbits being tested biweekly over every study period.
      The LLLT group received LLLT with a helium-neon (He-Ne) laser (830 nm) of 1.5
      J/cm(2) three times per week, and the ACLT group received placebo LLLT with the
      equipment switched off. Long-term and short-term pain was tested via weight
      bearing asymmetry; synovitis was assessed histologically; and knee joint
      cartilage was evaluated by gross morphology, histology, and gene expression
      analysis of anabolic and catabolic factors. The histological assessment of pain
      and synovitis showed that at least 6-week intermittent irradiation of LLLT could
      relief knee pain and control synovium inflammation. Gross morphologic inspection
      and histological evaluation showed that 6 weeks of LLLT could decrease cartilage
      damage of medical femoral condyle and 8 weeks of LLLT could decrease cartilage
      damage of medical and lateral femoral condyles and medical tibial plateau. Gene
      expression analysis revealed two results: At least 6 weeks of LLLT could decrease
      production of catabolic factors, for example, interleukin 1beta (IL-1beta),
      inducible nitric oxide synthase (iNOS), and MMP-3, and slow down the loss of
      anabolic factors, mainly TIMP-1. Eight weeks of LLLT treatment could slow down
      the loss of collagen II, aggrecan, and anabolic factors, mainly transforming
      growth factor beta (TGF-beta). The study suggests that LLLT plays a protective
      role against cartilage degradation and synovitis in rabbits with progressive OA
      by virtue of the regulation of catabolic and anabolic factors in the cartilage.

PMID- 24890037
TI  - Reward anticipation and processing of social versus nonsocial stimuli in children
      with and without autism spectrum disorders.
AB  - BACKGROUND: How children respond to social and nonsocial rewards has important
      implications for both typical and atypical social-cognitive development.
      Individuals with autism spectrum disorders (ASD) are thought to process rewards
      differently than typically developing (TD) individuals. However, there is little
      direct evidence to support this claim. METHODS: Two event-related potentials were
      measured. The stimulus preceding negativity (SPN) was utilized to measure reward
      anticipation, and the feedback related negativity (FRN) was utilized to measure
      reward processing. Participants were 6- to 8-year-olds with (N = 20) and without
      (N = 23) ASD. Children were presented with rewards accompanied by incidental face
      or nonface stimuli. Nonface stimuli were composed of scrambled face elements in
      the shape of arrows, controlling for low-level visual properties. RESULTS:
      Children with ASD showed smaller responses while anticipating and processing
      rewards accompanied by social stimuli than TD children. Anticipation and
      processing of rewards accompanied by nonsocial stimuli was intact in children
      with ASD. CONCLUSIONS: This is the first study to measure both reward
      anticipation and processing in ASD while controlling for reward properties. The
      findings provide evidence that children with autism have reward anticipation and
      processing deficits for social stimuli only. Our results suggest that while
      typically developing children find social stimuli more salient than nonsocial
      stimuli, children with ASD may have the opposite preference.

PMID- 24890039
TI  - Reconceiving masculinity and 'men as partners' for ICPD Beyond 2014: insights
      from a Mexican HPV study.
AB  - Men are poorly integrated into sexual and reproductive health programmes, despite
      long-standing calls for their inclusion. From the 1994 Cairo International
      Conference on Population and Development (ICPD) to the Policy Recommendations for
      the ICPD Beyond 2014, calls for 'rights for all' conflict with implicit,
      homogenising framing of men as patriarchal roadblocks to women's empowerment.
      This framing generates ambivalence about providing men's services, leading to
      emphasis on 'men as partners' supporting women's autonomous reproductive health
      decision-making rather than attention to both sexes' health needs. We argue that
      this framing also belies both the global rise of self-consciously non-traditional
      masculinities, and the fact that people's ostensibly individual sexual and
      reproductive health practices are profoundly relational. Here, we reimagine the
      concept of 'partnering' as an analytic for understanding how lived relationships
      influence both men's and women's sexual and reproductive practice. 'Partnering'
      in this sense is the context-dependent collaboration through which a range of
      gendered actors, not limited to male-female dyads, interact to shape health
      behaviour. We apply this approach to Mexican men's participation in a medical
      research on human papillomavirus transmission, demonstrating how spouses jointly
      refashioned male-focused health surveillance into familial health care and a
      forum for promoting progressive gender norms to their children and the broader
      society. 

PMID- 24890038
TI  - Overestimation of knowledge about word meanings: the "misplaced meaning" effect.
AB  - Children and adults may not realize how much they depend on external sources in
      understanding word meanings. Four experiments investigated the existence and
      developmental course of a "Misplaced Meaning" (MM) effect, wherein children and
      adults overestimate their knowledge about the meanings of various words by
      underestimating how much they rely on outside sources to determine precise
      reference. Studies 1 and 2 demonstrate that children and adults show a highly
      consistent MM effect, and that it is stronger in young children. Study 3
      demonstrates that adults are explicitly aware of the availability of outside
      knowledge, and that this awareness may be related to the strength of the MM
      effect. Study 4 rules out general overconfidence effects by examining a
      metalinguistic task in which adults are well calibrated. 

PMID- 24890040
TI  - A study of the determinants of work-to-family conflict among hospital nurses in
      Belgium.
AB  - AIMS: This study examines the relative impact of three sources of work-to-family
      conflict among hospital nurses: work-family policy use (childcare assistance,
      schedule flexibility, part-time work), job dimensions (work overload, job
      autonomy, overtime hours, night shifts, regularity in type of shift, weekend
      work, hierarchical position, variation in tasks) and organisational support
      (physician/co-worker support). BACKGROUND: Many studies claim that organisational
      support and job dimensions are more important sources of work-to-family conflict
      than work-family policy use, a relation that has not been fully investigated.
      This study attempts to fill this gap by empirically assessing the relative impact
      of these sources on nurses' work-to-family conflict. METHODS: Four hundred and
      fifty three Belgian nurses completed a web survey. The sources of work-to-family
      conflict were analysed using a hierarchical linear regression. RESULTS:
      Organisational support influences work-to-family conflict, above and beyond work
      family policy use and job dimensions, while policy use has no influence.
      Physician and co-worker support have a unique decreasing effect, while work
      overload and overtime hours increase work-to-family conflict. CONCLUSIONS:
      Organisational support, lack of work overload and absence of overtime hours
      reduce work-to-family conflict, whereas work-family policy use does not.
      IMPLICATIONS FOR NURSING MANAGEMENT: To retain and attract nurses by reducing
      work-to-family conflict, hospitals should not (only) rely on work-family policies
      but should also invest in organisational support and adapted job dimensions.

PMID- 24890042
TI  - Macroalgal blooms alter community structure and primary productivity in marine
      ecosystems.
AB  - Eutrophication, coupled with loss of herbivory due to habitat degradation and
      overharvesting, has increased the frequency and severity of macroalgal blooms
      worldwide. Macroalgal blooms interfere with human activities in coastal areas,
      and sometimes necessitate costly algal removal programmes. They also have many
      detrimental effects on marine and estuarine ecosystems, including induction of
      hypoxia, release of toxic hydrogen sulphide into the sediments and atmosphere,
      and the loss of ecologically and economically important species. However,
      macroalgal blooms can also increase habitat complexity, provide organisms with
      food and shelter, and reduce other problems associated with eutrophication. These
      contrasting effects make their overall ecological impacts unclear. We conducted a
      systematic review and meta-analysis to estimate the overall effects of macroalgal
      blooms on several key measures of ecosystem structure and functioning in marine
      ecosystems. We also evaluated some of the ecological and methodological factors
      that might explain the highly variable effects observed in different studies.
      Averaged across all studies, macroalgal blooms had negative effects on the
      abundance and species richness of marine organisms, but blooms by different algal
      taxa had different consequences, ranging from strong negative to strong positive
      effects. Blooms' effects on species richness also depended on the habitat where
      they occurred, with the strongest negative effects seen in sandy or muddy
      subtidal habitats and in the rocky intertidal. Invertebrate communities also
      appeared to be particularly sensitive to blooms, suffering reductions in their
      abundance, species richness, and diversity. The total net primary productivity,
      gross primary productivity, and respiration of benthic ecosystems were higher
      during macroalgal blooms, but blooms had negative effects on the productivity and
      respiration of other organisms. These results suggest that, in addition to their
      direct social and economic costs, macroalgal blooms have ecological effects that
      may alter their capacity to deliver important ecosystem services. 

PMID- 24890043
TI  - Hydrogenation of esters to alcohols with a well-defined iron complex.
AB  - We present the first base-free Fe-catalyzed ester reduction applying molecular
      hydrogen. Without any additives, a variety of carboxylic acid esters and lactones
      were hydrogenated with high efficiency. Computations reveal an outer-sphere
      mechanism involving simultaneous hydrogen transfer from the iron center and the
      ligand. This assumption is supported by NMR experiments. 

PMID- 24890044
TI  - A tantalum nitride photoanode modified with a hole-storage layer for highly
      stable solar water splitting.
AB  - Photoelectrochemical (PEC) water splitting is an ideal approach for renewable
      solar fuel production. One of the major problems is that narrow bandgap
      semiconductors, such as tantalum nitride, though possessing desirable band
      alignment for water splitting, suffer from poor photostability for water
      oxidation. For the first time it is shown that the presence of a ferrihydrite
      layer permits sustainable water oxidation at the tantalum nitride photoanode for
      at least 6 h with a benchmark photocurrent over 5 mA cm(-2) , whereas the bare
      photoanode rapidly degrades within minutes. The remarkably enhanced
      photostability stems from the ferrihydrite, which acts as a hole-storage layer.
      Furthermore, this work demonstrates that it can be a general strategy for
      protecting narrow bandgap semiconductors against photocorrosion in solar water
      splitting. 

PMID- 24890041
TI  - Combination of 9-aminoacridine with Campath-1H provides effective therapy for a
      murine model of adult T-cell leukemia.
AB  - BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of
      CD4+CD25+ lymphocytes caused by human T-cell lymphotropic virus type 1. While
      much progress has been made in understanding the mechanisms of cellular
      dysregulation, the prognosis for aggressive ATL still remains poor. Therefore,
      new therapeutic approaches need to be developed. RESULTS: Previously, we
      demonstrated that the viral protein Tax inactivates p53 in HTLV-1-infected T
      cells. Here we show that 9-aminoacridine (9AA) through p53 reactivation and NF
      kappaB inhibition has selective toxicity for infected leukemic cells independent
      of their p53 status. We further demonstrate that 9AA activates caspase-3/7
      resulting in PARP cleavage. Next we investigated the efficacy of 9AA in the MET-1
      ATL model. Alone, 9AA did not cause significant drops in surrogate tumor markers,
      soluble IL-2Ralpha or beta2-micorglobulin (beta2MU) levels with only a slight
      increase in survival of MET-1-bearing mice. However, in combination with Campath
      1H, 9AA treatment resulted in low soluble IL-2Ralpha and beta2MU levels at 2 and
      4 weeks. Consistent with reduced tumor cell burden, combination treatment
      significantly increased survival of MET-1-bearing mice compared to mice treated
      with either drug alone. Splenic cells isolated from 9AA or combination treated
      mice showed increased p53 protein levels and transcriptional activity. Consistent
      with increased tumor suppressor activity, we found increased PARP-1 cleavage in
      9AA and combination treated cells. CONCLUSION: Our results indicate that
      targeting reactivation of p53 and inhibition of NF-kappaB with acridine
      derivatives in combination with other chemotherapeutics could result in increased
      efficacy and selective killing of tumor cells.

PMID- 24890045
TI  - Review article: chemokines as orchestrators of autoimmune hepatitis and potential
      therapeutic targets.
AB  - BACKGROUND: Chemokines contribute to the pathogenesis of autoimmune hepatitis by
      directing the migration and positioning of inflammatory and immune cells within
      the liver. AIM: Describe the liver-infiltrating effector cell populations in
      autoimmune hepatitis, indicate the chemokines that influence their migration,
      describe the role of chemokines in hepatic fibrosis and identify chemokine
      directed treatment opportunities. METHODS: Studies cited in Pub Med from 1972 to
      2014 for autoimmune hepatitis, chemokines in liver disease, pathogenesis of
      autoimmune hepatitis and chemokine therapy were selected. RESULTS: T helper type
      17 lymphocytes expressing CXCR3 and CCR6 are attracted to the liver by the
      secretion of CXCL9, CXCL10 and CXCL11. These cells recruit pro-inflammatory T
      helper type 1 lymphocytes expressing CXCR3 and CCR5 by secreting CXCL10. Resident
      natural killer T cells expressing CXCR6 migrate in response to the local
      secretion of CXCL16, and they modulate the inflammatory response. T helper type 2
      lymphocytes expressing CCR4 are attracted by CCL17 and CCL22, and they dampen the
      expansion of pro-inflammatory cells. Regulatory T cells expressing CXCR3 are
      attracted by the secretion of CXCL9, and they help dampen the pro-inflammatory
      responses. CCL2, CCL3, CCL5, CXCL4, CXCL10 and CXCL16 promote fibrosis by
      activating or attracting hepatic stellate cells, and CX3CL1 may prevent fibrosis
      by affecting the apoptosis of monocytes. CONCLUSIONS: Chemokines are requisites
      for mobilising, directing and positioning the effector cells in immune-mediated
      liver disease. They are feasible therapeutic targets in autoimmune hepatitis, and
      the evaluation of monoclonal antibodies that neutralise the pro-inflammatory
      ligands or designer peptides that block receptor activity are investigational
      opportunities.

PMID- 24890046
TI  - Gene regulation: Chanzyme in action--divide and conquer?

PMID- 24890047
TI  - Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor
      characteristics in the European Prospective Investigation into Cancer and
      Nutrition.
AB  - The role of endogenous androgens and sex hormone-binding globulin (SHBG) in
      ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer
      (EOC) is a heterogeneous disease and there are no prospective data on endogenous
      androgens and EOC risk by tumor characteristics (histology, grade, stage) or the
      dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to
      less or more aggressive tumors). We conducted a nested case-control study in the
      European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
      evaluating androgens and SHBG and invasive EOC risk by tumor characteristics.
      Female participants who provided a blood sample and were not using exogenous
      hormones at blood donation were eligible (n = 183,257). A total of 565 eligible
      women developed EOC; two controls (n = 1,097) were matched per case. We used
      multivariable conditional logistic regression models. We observed no association
      between androgens, SHBG and EOC overall. A doubling of androstenedione reduced
      risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence
      interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and
      high-grade carcinomas, with positive associations for low-grade and inverse
      associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 =
      1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet <= 0.01), similar
      associations were observed for type I/II tumors. This is the first prospective
      study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type
      I/II status. Our findings support a possible role of androgens in ovarian
      carcinogenesis. Additional studies exploring this association are needed.

PMID- 24890049
TI  - Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin
      scaffolds: evaluation of the effect of leukocyte inclusion.
AB  - The potential influence of leukocyte incorporation in the kinetic release of
      growth factors from platelet-rich plasma (PRP) may explain the conflicting
      efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue
      regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP
      fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine
      release kinetics were analyzed. Clots were incubated with culture medium to
      monitor protein release over 8 days. Furthermore, the different fibrin scaffolds
      were morphologically characterized. Results show that leukocyte-free fibrin
      matrices were homogenous while leukocyte-containing ones were heterogeneous,
      loose and cellular. Leukocyte incorporation produced a significant increase in
      the contents of proinflammatory cytokines interleukin (IL)-1beta and IL-16 but
      not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the
      availability of vascular endothelial growth factor suffered an important decrease
      after 3 days of incubation in the case of L-PRP matrices. While the release of
      proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the
      inclusion of leukocytes induced a major increase in these cytokines, which was
      characterized by the presence of a latent period. The PRGF-Endoret matrices were
      stable during the 8 days of incubation. The inclusion of leukocytes alters the
      growth factors release profile and also increased the dose of proinflammatory
      cytokines.

PMID- 24890048
TI  - Direct allylation of aromatic and alpha,beta-unsaturated carboxamides under
      ruthenium catalysis.
AB  - The ruthenium-catalyzed oxidative allylation of aromatic and alpha,beta
      unsaturated carboxamides with allylic carbonates is described. These
      transformations proceed readily with complete linear gamma-selectivity of
      substituted allylic carbonates. 

PMID- 24890050
TI  - The influence of athletic status on maximal and rapid isometric torque
      characteristics and postural balance performance in Division I female soccer
      athletes and non-athlete controls.
AB  - The purpose of this study was to examine the effectiveness of maximal and rapid
      isometric torque characteristics of the hip extensor muscles and postural balance
      performance to discriminate between female collegiate soccer athletes and non
      athlete controls. Ten athletes (mean +/- SE: age = 19.20 +/- 0.36 year; mass =
      62.23 +/- 3.12 kg; height = 162.43 +/- 1.70 cm) and 10 non-athletes (age = 20.30
      +/- 0.40 year; mass = 69.64 +/- 3.20 kg; height = 163.22 +/- 2.10 cm) performed
      two isometric maximal voluntary contractions (MVCs) of the hip extensor muscles.
      Peak torque (PT) and absolute and relative rate of torque development (RTD) at
      early (0-50 ms) and late (100-200 ms) phases of muscle contraction were examined
      during each MVC. Postural balance was assessed using a commercially designed
      balance testing device, which provides a measurement of static stability based on
      sway index (SI). Results indicated that absolute and relative RTD at 0-50 ms
      (RTD50 and RTD50norm) were greater (P = 0.007 and 0.026), and postural SI was
      lower (P = 0.022) in the athletes compared with the non-athletes. However, no
      differences (P = 0.375-0.709) were observed for PT nor absolute and relative RTD
      at 100-200 ms (RTD100-200 and RTD100-200norm). Significant relationships were
      also observed between RTD50 and RTD50norm and SI (r = -0.559 and -0.521; P =
      0.010 and 0.019). These findings suggest that early rapid torque characteristics
      of the hip extensor muscles and postural balance performance may be sensitive and
      effective measures for discriminating between college-aged athletes and non
      athletes. Coaches and practitioners may use these findings as performance
      evaluation tools to help in identifying athletes with both superior early rapid
      torque and balance performance abilities, which may possibly be an indicator of
      overall athletic potential. 

PMID- 24890051
TI  - Early surgical intervention in severe acute pancreatitis: Central Australian
      experience.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) is a disease associated with a high
      mortality and morbidity; however, many patients survive due to better
      understanding of the disease and multidisciplinary care. Those who do not respond
      to intensive care management with persistent multi-organ dysfunction still have a
      high mortality. There is a role for early surgical intervention in two subsets of
      critically ill patients: the first, with acute compartment syndrome (ACS) of the
      abdomen with persisting organ dysfunction despite medical measures to control
      intra-abdominal pressure; the second, being early infected pancreatic necrosis
      (IPN) with the presence of gas in the retroperitoneum. METHODS: The current
      analysis is an 8-year (2005-2012) study. The data were collected prospectively by
      the Surgical Department in Alice Springs Hospital. Intensive care data were also
      sourced from ANZICS CORE (Australia and New Zealand Intensive Care Society and
      Centre for Outcome and Resource Evaluation) for ICU (intensive care unit)
      mortality comparison between ICUs of Australia and New Zealand with Alice
      Springs. RESULTS: There were 1163 episodes of acute pancreatitis with an annual
      incidence of 275 per 100 000. Of importance, 114 patients had SAP of whom 42
      developed pancreatic necrosis. Eleven patients required surgical intervention.
      Five patients had decompressive laparotomies for ACS and six patients had
      laparotomies for IPN. The mortality of patients with SAP was 0%. CONCLUSIONS: The
      two subsets of patients with either ACS or early IPN require early surgical
      intervention either by decompressive laparotomy or open necrosectomy with
      laparostomy. The authors attribute improved survival in this cohort due to these
      interventions.

PMID- 24890052
TI  - Social neuroscience as an ideal basic science for psychiatry.

PMID- 24890053
TI  - WHO's Mental Health Action Plan 2013-2020: what can psychiatrists do to
      facilitate its implementation?

PMID- 24890054
TI  - Taking the long view: an emerging framework for translational psychiatric
      science.
AB  - Understood in their historical context, current debates about psychiatric
      classification, prompted by the publication of the DSM-5, open up new
      opportunities for improved translational research in psychiatry. In this paper,
      we draw lessons for translational research from three time slices of 20th century
      psychiatry. From the first time slice, 1913 and the publication of Jaspers'
      General Psychopathology, the lesson is that translational research in psychiatry
      requires a pluralistic approach encompassing equally the sciences of mind
      (including the social sciences) and of brain. From the second time slice, 1959
      and a conference in New York from which our present symptom-based classifications
      are derived, the lesson is that, while reliability remains the basis of
      psychiatry as an observational science, validity too is essential to effective
      translation. From the third time slice, 1997 and a conference on psychiatric
      classification in Dallas that brought together patients and carers with
      researchers and clinicians, the lesson is that we need to build further on
      collaborative models of research combining expertise-by-training with expertise
      by-experience. This is important if we are to meet the specific challenges to
      translation presented by the complexity of the concept of mental disorder,
      particularly as reflected in the diversity of desired treatment outcomes. Taken
      together, these three lessons - a pluralistic approach, reliability and validity,
      and closer collaboration among relevant stakeholders - provide an emerging
      framework for more effective translation of research into practice in 21st
      century psychiatry. 

PMID- 24890055
TI  - New trends in assessing the outcomes of mental health interventions.
AB  - Assessing the outcomes of interventions in mental health care is both important
      and challenging. The aim of this paper is to advance the field of outcomes
      research by proposing a taxonomy of the decisions that clinicians and researchers
      need to consider when evaluating outcomes. Our taxonomy has eight components,
      framed as decisions: Whose outcome will be considered? Which scientific stage is
      being investigated? What outcome domain(s) matter? What level of assessment will
      be used? Will clinical and/or recovery outcomes be assessed? Whose perspective
      will be considered? Will deficits and/or strengths be the focus? Will invariant
      or individualized measures be preferred? We propose a future focus on
      understanding what matters most to people using mental health services, and on
      the use of measures rated by service users as the primary approach to evaluating
      outcome. 

PMID- 24890056
TI  - Impulse control disorders and "behavioural addictions" in the ICD-11.

PMID- 24890057
TI  - Suicidal behavior disorder as a diagnostic entity in the DSM-5 classification
      system: advantages outweigh limitations.

PMID- 24890059
TI  - Social neuroscience: bringing an end to the destructive and misguided "social"
      versus "biological" in psychiatry.

PMID- 24890060
TI  - Will better psychiatric treatments emerge from top-down or bottom-up
      neuroscientific studies of affect?

PMID- 24890058
TI  - Social neuroscience and its potential contribution to psychiatry.
AB  - Most mental disorders involve disruptions of normal social behavior. Social
      neuroscience is an interdisciplinary field devoted to understanding the
      biological systems underlying social processes and behavior, and the influence of
      the social environment on biological processes, health and well-being. Research
      in this field has grown dramatically in recent years. Active areas of research
      include brain imaging studies in normal children and adults, animal models of
      social behavior, studies of stroke patients, imaging studies of psychiatric
      patients, and research on social determinants of peripheral neural,
      neuroendocrine and immunological processes. Although research in these areas is
      proceeding along largely independent trajectories, there is increasing evidence
      for connections across these trajectories. We focus here on the progress and
      potential of social neuroscience in psychiatry, including illustrative evidence
      for a rapid growth of neuroimaging and genetic studies of mental disorders. We
      also argue that neuroimaging and genetic research focused on specific component
      processes underlying social living is needed. 

PMID- 24890061
TI  - Social neuroscience and mechanisms of risk for mental disorders.

PMID- 24890062
TI  - The brain's intrinsic activity and inner time consciousness in schizophrenia.

PMID- 24890063
TI  - Social neuroscience in psychiatry: pathways to discovering neurobiological risk
      and resilience.

PMID- 24890064
TI  - Social neuroscience in psychiatry: of obvious relevance.

PMID- 24890065
TI  - Bridging psychiatry and neurology through social neuroscience.

PMID- 24890066
TI  - Loneliness and social neuroscience.

PMID- 24890067
TI  - Psychiatry and social nutritional neuroscience.

PMID- 24890069
TI  - Effectiveness of programs for reducing the stigma associated with mental
      disorders. A meta-analysis of randomized controlled trials.
AB  - The stigma associated with mental disorders is a global public health problem.
      Programs to combat it must be informed by the best available evidence. To this
      end, a meta-analysis was undertaken to investigate the effectiveness of existing
      programs. A systematic search of PubMed, PsycINFO and Cochrane databases yielded
      34 relevant papers, comprising 33 randomized controlled trials. Twenty-seven
      papers (26 trials) contained data that could be incorporated into a quantitative
      analysis. Of these trials, 19 targeted personal stigma or social distance (6,318
      participants), six addressed perceived stigma (3,042 participants) and three self
      stigma (238 participants). Interventions targeting personal stigma or social
      distance yielded small but significant reductions in stigma across all mental
      disorders combined (d=0.28, 95% CI: 0.17-0.39, p<0.001) as well as for depression
      (d=0.36, 95% CI: 0.10-0.60, p<0.01), psychosis (d=0.20, 95% CI: 0.06-0.34,
      p<0.01) and generic mental illness (d=0.30, 95% CI: 0.10-0.50, p<0.01).
      Educational interventions were effective in reducing personal stigma (d=0.33, 95%
      CI: 0.19-0.42, p<0.001) as were interventions incorporating consumer contact
      (d=0.47, 95% CI: 0.17-0.78, p<0.001), although there were insufficient studies to
      demonstrate an effect for consumer contact alone. Internet programs were at least
      as effective in reducing personal stigma as face-to-face delivery. There was no
      evidence that stigma interventions were effective in reducing perceived or self
      stigma. In conclusion, there is an evidence base to inform the roll out of
      programs for improving personal stigma among members of the community. However,
      there is a need to investigate methods for improving the effectiveness of these
      programs and to develop interventions that are effective in reducing perceived
      and internalized stigma. 

PMID- 24890068
TI  - Risks of all-cause and suicide mortality in mental disorders: a meta-review.
AB  - A meta-review, or review of systematic reviews, was conducted to explore the
      risks of all-cause and suicide mortality in major mental disorders. A systematic
      search generated 407 relevant reviews, of which 20 reported mortality risks in 20
      different mental disorders and included over 1.7 million patients and over a
      quarter of a million deaths. All disorders had an increased risk of all-cause
      mortality compared with the general population, and many had mortality risks
      larger than or comparable to heavy smoking. Those with the highest all-cause
      mortality ratios were substance use disorders and anorexia nervosa. These higher
      mortality risks translate into substantial (10-20 years) reductions in life
      expectancy. Borderline personality disorder, anorexia nervosa, depression and
      bipolar disorder had the highest suicide risks. Notable gaps were identified in
      the review literature, and the quality of the included reviews was typically low.
      The excess risks of mortality and suicide in all mental disorders justify a
      higher priority for the research, prevention, and treatment of the determinants
      of premature death in psychiatric patients. 

PMID- 24890070
TI  - Predictors of type 2 diabetes in a nationally representative sample of adults
      with psychosis.
AB  - Antipsychotic drugs such as clozapine and olanzapine are associated with an
      increased risk for type 2 diabetes, but relatively little is known about the
      relationship between risk factors for type 2 diabetes established in the general
      population and type 2 diabetes in people with psychosis. We estimated the
      prevalence of established risk factors and their association with type 2 diabetes
      in a nationally representative sample of people with an ICD-10 psychosis (N=1642)
      who gave a fasting blood sample (N=1155). Logistic regression was used to
      summarize associations adjusted for age and sex. In this sample, whose mean
      duration of psychosis was 14.7 years, 12.1% (13.1% of women and 11.5% of men) had
      type 2 diabetes at age 18-64 years based on current fasting blood glucose levels
      or treatment with a hypoglycaemic drug. Risk was greatly increased in young
      adults compared with the general population and peaked in middle age. Risk
      factors in the general population were common in people with psychosis and
      strongly associated with type 2 diabetes in those people. Treatment with
      clozapine was associated with an increased risk and treatment with olanzapine
      with a decreased risk for type 2 diabetes. The development of diabetes or pre
      diabetes may therefore influence the likelihood of treatment with olanzapine over
      time. The strongest predictors of type 2 diabetes in a multivariate model were a
      body mass index of at least 40 and treated hypercholesterolemia, followed by a
      body mass index between 35 and 39.9, a family history of diabetes and treated
      hypertension. There was minimal to no confounding of the association between type
      2 diabetes and current clozapine or olanzapine treatment, but neither association
      remained significant after adjustment for other predictors. Longitudinal
      relationships among predictors are likely to be complex, and previous
      antipsychotic drug treatment may at least partly explain risks associated with
      severe obesity, dyslipidemia and hypertension. A focus on weight loss is
      warranted in people with psychosis, but prevention strategies for type 2 diabetes
      should be broadened to include those with emerging dyslipidemia, hypertension and
      a family history of diabetes. 

PMID- 24890071
TI  - Psychotic experiences as a predictor of the natural course of suicidal ideation:
      a Swedish cohort study.
AB  - Psychotic experiences are far more prevalent in the population than psychotic
      disorders and are associated with a wide range of depressive, anxiety and
      behavioral disorders, as well as increased risk for psychotic disorder. Recently,
      psychotic experiences have been highlighted as a potentially valuable clinical
      marker of risk for suicidal behavior. There have been few studies to date,
      however, to assess psychotic experiences as a predictor of suicidality over time.
      We wished to assess whether young persons with suicidal ideation at baseline
      assessment who reported psychotic experiences were at higher risk for persistence
      of suicidal ideation at follow-up than young persons who also reported suicidal
      ideation at baseline but who did not report co-occurring psychotic experiences. A
      total of 2,263 adolescents were assessed at age 13 to 14 years for psychotic
      experiences, suicidal ideation and internalizing and externalizing
      psychopathology. Participants were re-assessed at ages 16 to 17 years and 19 to
      20 years. Among 13- to 14-year olds with suicidal ideation, co-occurring
      psychotic experiences did not predict an increased odds of persistence of
      suicidal ideation to age 16 to 17 years (OR=0.94, 95% CI: 0.19-4.78). Among 16-
      to 17-year olds with suicidal ideation, however, co-occurring psychotic
      experiences predicted a 6-fold increased odds of persistence of suicidal ideation
      to age 19 to 20 years (OR=5.53, 95% CI: 1.33-23.00). Psychotic experiences are an
      important but under-recognized marker of risk for persistence of suicidal
      ideation, in particular from mid-adolescence. An increased emphasis on the
      clinical assessment of psychotic experiences in mental health services should be
      a priority. 

PMID- 24890072
TI  - Markers of inflammation in schizophrenia: association vs. causation.

PMID- 24890073
TI  - Management of obesity in the psychiatrist's office.

PMID- 24890074
TI  - The RDoC framework: continuing commentary.

PMID- 24890075
TI  - Global priorities of civil society for mental health services: findings from a 53
      country survey.

PMID- 24890077
TI  - When psychiatrists are forced to deal with religion in daily practice.

PMID- 24890076
TI  - Are antidepressants clinically useful? Conclusion of a decade of debate.

PMID- 24890078
TI  - News from WPA Scientific Sections.

PMID- 24890079
TI  - Proposals for ICD-11: a report for WPA membership.

PMID- 24890080
TI  - Response to "A Patient-Centered Approach to Clinical Practice Guidelines in
      Otolaryngology".

PMID- 24890081
TI  - Autologous Fat Injection Combined with Palatoplasty and Pharyngoplasty for
      Velopharyngeal Insufficiency and Cleft Palate: Preliminary Experience.

PMID- 24890082
TI  - Histopathological mapping of metastatic tumor cells in sentinel lymph nodes of
      oral and oropharyngeal squamous cell carcinomas.
AB  - BACKGROUND: Sentinel lymph node biopsy is a reliable technique for accurate
      determination of the cervical lymph node status in patients with early oral and
      oropharyngeal cancer but analyses on the distribution pattern of metastatic
      spread within sentinel lymph nodes are lacking. METHODS: The localizations of
      carcinoma deposits were analyzed with a virtual microscope by creating digital
      images from the microscopic glass slides. RESULTS: Metastatic deposits were not
      randomly distributed within sentinel lymph nodes but were predominant in the
      central planes closer to the lymphatic inlet. Initial evaluation of the 4 most
      central slices achieved a high rate of 90% for the detection of micrometastases
      and of 80% for the detection of isolated tumor cells (ITCs). CONCLUSION: Based on
      the distribution we recommend an initial cut through the hilus and to proceed
      with the 4 most central 150-um slices. Complete step sectioning is only required
      in case of a so far negative result.

PMID- 24890083
TI  - Assessment of the elicitation response in subjects weakly sensitized to p
      phenylenediamine.
AB  - BACKGROUND: A 30-min application of a hair dye product containing 2% p
      phenylenediamine (PPD) to subjects diagnostically graded +, showed that 12 of 18
      reacted; eight of 18 with a true + and four of 18 with a doubtful (?+) response,
      whereas six of 18 did not react at all. In vitro skin-binding experiments showed
      that for diagnostic patch test conditions the measured exposure level (MEL) is
      more than 10-fold higher than the MEL for hair dyeing conditions. OBJECTIVE: To
      further analyse the limited elicitation response of the diagnostically + graded
      subjects to a PPD hair dye product, under standardized test conditions mimicking
      product usage, by varying exposure time and dose. METHODS: A hair dye model
      formulation containing 2% PPD, applied for 30, 45 and 60 min and a diagnostic PPD
      TRUE test((r)) were applied to assess elicitation responses to increasing PPD
      exposure levels. Grading was performed according to International Contact
      Dermatitis Research Group guidelines. RESULTS: Six subjects were available for
      this follow-up study. One of six subjects responded with a + elicitation response
      to the hair dye model applied for 60 min. Four of the five remaining subjects
      elicited a + response to the PPD TRUE test((r)) applied subsequently, while one
      of five responded doubtfully. CONCLUSIONS: Increasing the PPD exposure time
      twofold--resulting in a 5-6% increase of sensitivity of this hair dye model test-
      or further extending the exposure time 48-fold, was found sufficient to increase
      the MEL above the thresholds needed to elicit individuals with a + diagnostic PPD
      patch test who did not react to typical hair dye use conditions with a MEL of
      about 6.8 MUg cm-2. This analysis confirms that consideration of the MEL is a
      useful tool to better characterize thresholds of elicitation than consideration
      of the applied dose alone.

PMID- 24890084
TI  - Bicuspid aortic valves: diagnostic accuracy of standard axial 64-slice chest CT
      compared to aortic valve image plane ECG-gated cardiac CT.
AB  - OBJECTIVES: To assess the diagnostic accuracy of standard axial 64-slice chest CT
      compared to aortic valve image plane ECG-gated cardiac CT for bicuspid aortic
      valves. MATERIALS AND METHODS: The standard axial chest CT scans of 20 patients
      with known bicuspid aortic valves were blindly, randomly analyzed for (i) the
      appearance of the valve cusps, (ii) the largest aortic sinus area, (iii) the
      longest aortic cusp length, (iv) the thickest aortic valve cusp and (v) valve
      calcification. A second blinded reader independently analyzed the appearance of
      the valve cusps. Forty-two age- and sex-matched patients with known tricuspid
      aortic valves were used as controls. Retrospectively ECG-gated cardiac CT
      multiphase reconstructions of the aortic valve were used as the gold-standard.
      RESULTS: Fourteen (21%) scans were scored as unevaluable (7 bicuspid, 7
      tricuspid). Of the remainder, there were 13 evaluable bicuspid valves, ten of
      which showed an aortic valve line sign, while the remaining three showed a normal
      Mercedes-Benz appearance owing to fused valve cusps. The 35 evaluable tricuspid
      aortic valves all showed a normal Mercedes-Benz appearance (P=0.001). Kappa
      analysis=0.62 indicating good interobserver agreement for the aortic valve cusp
      appearance. Aortic sinus areas, aortic cusp lengths and aortic cusp thicknesses
      of >= 3.8 cm(2), 3.2 cm and 1.6mm respectively on standard axial chest CT best
      distinguished bicuspid from tricuspid aortic valves (P<0.0001 for all). Of
      evaluable scans, the sensitivity, specificity, positive and negative predictive
      values of standard axial chest CT in diagnosing bicuspid aortic valves was 77%
      (CI 0.54-1.0), 100%, 100% and 70% respectively. CONCLUSION: The aortic valve is
      evaluable in approximately 80% of standard chest 64-slice CT scans. Bicuspid
      aortic valves may be diagnosed on evaluable scans with good diagnostic accuracy.
      An aortic valve line sign, enlarged aortic sinuses and elongated, thickened valve
      cusps are specific CT features.

PMID- 24890085
TI  - Neonatal neurosonography.
AB  - Paediatric and particularly neonatal neurosonography still remains a mainstay of
      imaging the neonatal brain. It can be performed at the bedside without any need
      for sedation or specific monitoring. There are a number of neurologic conditions
      that significantly influence morbidity and mortality in neonates and infants
      related to the brain and the spinal cord; most of them can be addressed by
      ultrasonography (US). However, with the introduction of first CT and then MRI,
      neonatal neurosonography is increasingly considered just a basic first line
      technique that offers only orienting information and does not deliver much
      relevant information. This is partially caused by inferior US performance -
      either by restricted availability of modern equipment or by lack of specialized
      expertise in performing and reading neurosonographic scans. This essay tries to
      highlight the value and potential of US in the neonatal brain and briefly
      touching also on the spinal cord imaging. The common pathologies and their US
      appearance as well as typical indication and applications of neurosonography are
      listed. The review aims at encouraging paediatric radiologists to reorient there
      imaging algorithms and skills towards the potential of modern neurosonography,
      particularly in the view of efficacy, considering growing economic pressure, and
      the low invasiveness as well as the good availability of US that can easily be
      repeated any time at the bedside. 

PMID- 24890086
TI  - Ocular surface squamous neoplasia: to cut or not to cut.

PMID- 24890087
TI  - 'Looking beneath the surface'.

PMID- 24890088
TI  - Rupture of an extended mycotic aneurysm of the descending thoracic aorta in a
      multiple myeloma patient undergoing anti-myeloma therapy.
AB  - Infectious complications in patients with multiple myeloma remain the main cause
      of mortality because of disease-related immunodeficiency. A mycotic aortic
      aneurysm caused by Burkhoderia cepacia, which has been recognized as nosocomial
      pathogen in immunocompromised populations, is very rare and only few cases have
      been reported in the literature. We describe an unusual case of a ruptured
      mycotic aneurysm of the descending thoracic aorta with a DeBakey IIIb aortic
      dissection caused by Burkhoderia cepacia in a patient with active multiple
      myeloma during chemotherapy with anti-myeloma agents. Successful treatment of
      this mycotic aneurysm included appropriate antibiotic therapy and replacement of
      the aortic arch and the descending aorta for the extensive debridement of all
      infected aortas. This was followed by the wrapping of a prosthetic graft with a
      well-vascularized tissue flap of the greater omentum and of the latissimus dorsi
      muscle. 

PMID- 24890089
TI  - Evaluation of the new IASLC/ATS/ERS proposed classification of adenocarcinoma
      based on lepidic pattern in patients with pathological stage IA pulmonary
      adenocarcinoma.
AB  - BACKGROUND: The International association for the study of cancer
      (IASLC)/American thoracic society (ATS)/European respiratory society (ERS) has
      established a new subclassification of lung adenocarcinoma, especially for the
      lepidic pattern component, formerly called bronchioloalveolar adenocarcinoma
      (BAC). According to the new classification, BAC has been classified into the
      following 4 main subtypes: adenocarcinoma in situ (AIS), minimally invasive
      adenocarcinoma (MIA), invasive adenocarcinoma (IA), and variants of invasive
      adenocarcinoma (VIA). An observational study was conducted to validate this
      classification in patients with pathological stage IA pulmonary adenocarcinoma.
      PATIENTS AND METHODS: 147 patients treated for pathological stage IA lung
      adenocarcinoma by complete resection at Osaka University Medical Hospital from
      January 1993 to December 2002 were assessed. The tumor specimens of the cohort
      were classified into the 4 subgroups. In addition, these groups were compared for
      various prognostic factors. RESULTS: Adenocarcinoma in situ was observed in 30
      patients, MIA in 8, IA in 104, and VIA in 5 patients, with 5-year survival rates
      of 100, 100, 85.5, and 60.0 %, respectively. The relationship between the
      histological classification and K-ras mutation was significant (p < 0.001),
      especially when comparing the VIA group with the others (p ? 0.001). Ki67
      labeling indices were significantly different between the AIS and IA groups (p =
      0.040). CONCLUSIONS: This study validated the proposed IASLC/ATS/ERS
      classification for pulmonary adenocarcinoma in patients with pathological stage
      IA pulmonary adenocarcinoma. The difference between AIS and IA may depend on the
      proliferation of the carcinoma. In addition, the difference between VIA and the
      other adenocarcinoma types may depend on genetic factors, especially K-ras
      mutations.

PMID- 24890090
TI  - Thiazolidine-2,4-diones derivatives as PPAR-gamma agonists: synthesis, molecular
      docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk
      evaluation and effect on PPAR-gamma gene expression.
AB  - A library of conjugates of chromones and 2,4-thiazolidinedione has been
      synthesized by Knoevenagel condensation followed by reduction using hydrogen gas
      and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the
      blood glucose level comparable to standard drug pioglitazone. Compound 5e
      exhibited potent PPAR-gamma transactivation of 48.72% in comparison to
      pioglitazone (62.48%). All the molecules showed good glide score against the PPAR
      gamma target in molecular docking study. PPAR-gamma gene expression was
      significantly increased by compound 5e (2.56-fold) in comparison to standard drug
      pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may
      be considered as promising candidates for the development of new antidiabetic
      agents. 

PMID- 24890091
TI  - Morphological and molecular characterisation of Notosolenus urceolatus Larsen and
      Patterson 1990, a member of an understudied deep-branching euglenid group
      (petalomonads).
AB  - Petalomonads are particularly important for understanding the early evolution of
      euglenids, but are arguably the least studied major group within this taxon. We
      have established a culture of the biflagellate petalomonad Notosolenus
      urceolatus, and conducted electron microscopy observations and molecular
      phylogenetic analysis. Notosolenus urceolatus has eight pellicular strips
      bordered by grooves and underlain by close-set microtubules. There are ventral
      and dorsal Golgi bodies. Mitochondria apparently contain fibrous inclusions, as
      in Petalomonas cantuscygni. A previously undocumented type of large, globular
      extrusome is present instead of the tubular extrusomes characteristic of
      Euglenozoa. The feeding apparatus lacks rods and vanes, and is partly supported
      by an "MTR". The flagella have complex transition zones that are extremely
      elongated but unswollen. Only the emergent portion of the anterior flagellum has
      an organised paraxonemal rod, and also has very fine mastigonemes. The basal
      bodies are offset and lack connecting fibres. 18S rRNA gene phylogenies show that
      N. urceolatus is closely related to Petalomonas sphagnophila and P. cantuscygni,
      not Notosolenus ostium, confirming that current generic assignments based on the
      number of emergent flagella are phylogenetically unreliable, and making it
      difficult to infer whether features shared by N. urceolatus and P. cantuscygni
      (for example) are general for petalomonads. 

PMID- 24890092
TI  - Overexpression of flotillin-1 is involved in proliferation and recurrence of
      bladder transitional cell carcinoma.
AB  - Flotillin-1 (FLOT1) is known to have a role in tumorigenesis; however, the effect
      of FLOT1 on proliferation and recurrence of human transitional cell carcinoma
      (TCC) is unclear. Samples from 156 TCC patients and 142 patients undergoing open
      bladder surgery for indications other than TCC were used in the present study.
      FLOT1 protein expression was determined by immunohistochemistry and western blot
      analysis, and mRNA expression was detected by RT-PCR and real-time PCR. A FLOT1
      expressing pcDEF3 vector was stably transfected into 4 TCC cell lines and FLOT1
      expression was decreased by RNAi. Proliferative analysis of TCC cells was
      detected by the WST-1 assay and a xenograft model using BALB/C nude mice. The
      association between FLOT1 expression and TCC recurrence was also analyzed by
      adhesion, migration and invasion assays. FLOT1 expression in TCC was
      significantly overexpressed compared to normal urothelial tissue, and the level
      of FLOT1 expression was significantly correlated with tumor size, pathologic
      grade, clinical stage and recurrence. In addition, FLOT1 significantly increased
      the proliferative ability of TCC cells in vitro and in vivo. TCC cells with a
      high level of FLOT1 expression exhibited a higher level of adhesion, migration
      and invasion. FLOT1 expression was shown to be upregulated in human TCC. These
      findings suggest that FLOT1 plays an important role in the proliferation and
      recurrence of TCC and that silencing FLOT1 expression might be a novel
      therapeutic strategy.

PMID- 24890093
TI  - Prostate cancer screening rates remain stable despite recommendations against
      testing men with limited life expectancy.

PMID- 24890094
TI  - Spectral tuning in vertebrate short wavelength-sensitive 1 (SWS1) visual
      pigments: can wavelength sensitivity be inferred from sequence data?
AB  - The molecular mechanisms underlying the enormous diversity of visual pigment
      wavelength sensitivities found in nature have been the focus of many molecular
      evolutionary studies, with particular attention to the short wavelength-sensitive
      1 (SWS1) visual pigments that mediate vision in the ultraviolet to violet range
      of the electromagnetic spectrum. Over a decade of study has revealed that the
      remarkable extension of SWS1 absorption maxima (lambda max ) into the ultraviolet
      occurs through a deprotonation of the Schiff base linkage of the retinal
      chromophore, a mechanism unique to this visual pigment type. In studies of visual
      ecology, there has been mounting interest in inferring visual sensitivity at
      short wavelengths, given the importance of UV signaling in courtship displays and
      other behaviors. Since experimentally determining spectral sensitivities can be
      both challenging and time-consuming, alternative strategies such as estimating
      lambda max based on amino acids at sites known to affect spectral tuning are
      becoming increasingly common. However, these estimates should be made with
      knowledge of the limitations inherent in these approaches. Here, we provide an
      overview of the current literature on SWS1 site-directed mutagenesis spectral
      tuning studies, and discuss methodological caveats specific to the SWS1-type
      pigments. We focus particular attention on contrasting avian and mammalian SWS1
      spectral tuning mechanisms, which are the best studied among vertebrates. We find
      that avian SWS1 visual pigment spectral tuning mechanisms are fairly consistent,
      and therefore more predictable in terms of wavelength absorption maxima, whereas
      mammalian pigments are not well suited to predictions of lambda max from sequence
      data alone.

PMID- 24890095
TI  - Selection of a right posterior sector graft for living donor liver
      transplantation.
AB  - Right posterior sector (RPS) grafts have been used to overcome graft size
      discrepancies, the major concern of living donor liver transplantation. Previous
      studies have reported the volumetry-based selection of RPS grafts without
      anatomical exclusion. We reviewed our data and established selection criteria for
      RPS grafts. The procurement of RPS grafts [conventional (n = 3) and extended (n =
      5)] was performed for 8 of 429 recipients at our center. Extended RPS grafts
      contained the drainage area of the right hepatic vein. The mean graft weight (GW)
      according to 3-dimensional computed tomography volumetry was 488 g, and the
      GW/standard liver weight (SLW) ratio was 42.6%. The mean actual GW was 437 g, and
      the GW/SLW ratio was 38.4%. One donor exhibited standard bifurcation of the right
      portal vein (PV) and the left PV, and 2 donors exhibited trifurcation of the left
      PV, the right anterior portal vein (APV), and the posterior PV. The remaining 5
      donors exhibited APV branching from the left PV, which is the most suitable
      anatomy for RPS grafts. Two recipients died of sepsis or small-for-size graft
      syndrome. One underwent retransplantation because of an intractable bile leak and
      fibrosing cholestatic hepatitis. Intractable bile duct (BD) stenosis developed in
      4 of the 6 survivors. In conclusion, with the significant complications and
      potential concerns associated with RPS grafts, these grafts should be used very
      rarely and with extreme caution. Donors with the standard bifurcation of the PV
      and the posterior BD running through the dorsal side of the posterior PV are not
      suitable candidates for RPS grafts. Extended RPS graft procurement is recommended
      for easier parenchymal transection.

PMID- 24890096
TI  - Novel pharmacological approaches for the treatment of acne vulgaris.
AB  - INTRODUCTION: Acne vulgaris is the most common skin disease worldwide; yet,
      current treatment options, although effective, are associated with unwanted side
      effects, chronicity, relapses and recurrences. The adequate control of the four
      pathogenic mechanisms, involved in the appearance of acne lesions, is paramount
      to treatment success. AREAS COVERED: The authors discuss and evaluate the
      pathogenic pathways related to the mechanisms of action of novel molecules, which
      are currently under investigation for the treatment of acne vulgaris. The
      manuscript is based on comprehensive searches made through PubMed, GoogleScholar
      and ClinicalTrial.gov, using different combination of key words, which include
      acne vulgaris, pathogenesis, treatment, sebogenesis and Propionibacterium acnes.
      EXPERT OPINION: In the near future, more effective treatments with fewer side
      effects are expected. The use of topical antiandrogens, acetylcholine inhibitors
      and PPAR modulators seem to be promising options for controlling sebum
      production. Retinoic acid metabolism-blocking agents and IL-1alpha inhibitors
      have the potential to become legitimate alternative options to retinoid therapy
      in the management of infundibular dyskeratosis. Indeed, the authors believe that
      there will likely be a decline in the use of antibiotics for controlling P. acnes
      colonization and targeting the inflammation cascade.

PMID- 24890097
TI  - Food-specific serum IgE and IgG reactivity in dogs with and without skin disease:
      lack of correlation between laboratories.
AB  - BACKGROUND: Despite conflicting data on their utility and no reports on
      interlaboratory reproducibility, serum food-specific antibodies are commonly
      assayed in first-opinion canine practice. HYPOTHESIS/OBJECTIVES: To determine
      both the variability of test results between two laboratories and the frequencies
      and magnitudes of food reactivity in dogs of different disease status. ANIMALS:
      Sera were obtained from eight dogs with cutaneous adverse food reaction (Group
      A), 22 with nonfood-induced atopic dermatitis (Group B), 30 with an
      allergic/inflammatory phenotype (Group C), 12 with miscellaneous skin diseases
      (Group D) and nine healthy dogs (Group E). METHODS: Paired sera were submitted to
      two laboratories (A and B) for assays of food-specific IgE and IgG antibodies.
      RESULTS: Numbers of positive IgE and IgG tests determined by each laboratory in
      Groups A, B, D and E were comparable (Group C not included). Significant
      differences in the magnitude of IgE reactivity between groups for each allergen
      were seen only for lamb (Laboratory A, P = 0.003); lamb reactivity in Group D
      exceeded Group E (P = 0.004) but was comparable between all other groups.
      Agreement (kappa statistic) between the two laboratories' tests was 'moderate'
      for one antigen (potato IgE), 'fair' for four (corn IgE, rice IgE and IgG and
      soya bean IgG), 'slight' for eight (six IgE and two IgG) and 'less than chance'
      for the remaining six antigens (three IgE and three IgG). CONCLUSIONS AND
      CLINICAL IMPORTANCE: These laboratories' tests appear to have dubious predictive
      clinical utility because they neither correlate nor distinguish between dogs of
      different disease status.

PMID- 24890098
TI  - Quercetin intake with exercise modulates lipoprotein metabolism and reduces
      atherosclerosis plaque formation.
AB  - STUDY OBJECTIVES: We proposed that mice supplemented with quercetin, a class of
      flavonoids known to have antioxidant and anti-inflammatory properties, will have
      profound effects on the pathophysiology of atherosclerosis when combined with
      exercise. STUDY DESIGN: Forty C57BL6 LDLr -/- mice were divided into four groups
      (n = 10): control untreated (NN); control group supplemented with 100 MUg/day of
      quercetin (NQ); exercise group (EN); and exercise group supplemented with 100
      MUg/day of quercetin (EQ). All animals were fed atherogenic diet. The exercise
      groups were run on a treadmill for 30 minutes, 15 m/min for 5 days/week for 30
      days. After 30 day animals were sacrificed and tissues were harvested. RESULTS
      AND CONCLUSION: Mice supplemented with quercetin during exercise sessions had 78%
      atherosclerotic plaque reduction compared to control mice and 40% less
      atherosclerotic plaque formation compared to control group supplemented with
      quercetin. The manifestation of the combination of quercetin supplementation with
      exercise was more evident in the pro-reverse cholesterol transport genes,
      indicating a plausible mechanism for their combined beneficial effect. The
      pathogenesis of atherosclerosis, the major cause of cardiovascular diseases
      (CVD), is multifactorial and therefore its treatment approaches and the ability
      to regress the plaque are complicated. Data from research on animal models and
      clinical studies have indicated that moderate daily exercise can alleviate the
      risk for the development of atherosclerotic plaques, while the same has not been
      true for the supplementation of antioxidants.

PMID- 24890100
TI  - Investigating dynamic pain sensitivity in the context of the fear-avoidance
      model.
AB  - BACKGROUND: Although nearly everyone at some point in their lives experiences
      back pain; the amount of interference with routine activity varies significantly.
      The fear-avoidance (FA) model of chronic pain explains how psychological
      variables, such as fear, act as mediating factors influencing the relationship
      between clinical pain intensity and the amount of interference with daily
      activities. What remains less clear is how other mediating factors fit within
      this model. The primary objective of this report was to examine the extent to
      which a dynamic measure of pain sensitivity provides additional information
      within the context of the FA model. METHOD: To address our primary objective,
      classic mediation and moderated mediation analyses were conducted on baseline
      clinical, psychological and quantitative sensory measures obtained on 67 subjects
      with back pain (mean age, 31.4 +/- 12.1 years; 70% female). RESULTS: There was a
      moderately strong relationship (r = 0.52; p < 0.01) between clinical pain
      intensity and interference, explaining about 27% of the variance in the outcome.
      Mediation analyses confirmed fear partially mediated the total effect of clinical
      pain intensity on interference (Deltabeta = 0.27; p < 0.01), and accounted for an
      additional 16% of the variance. In our FA model, pain sensitivity did not
      demonstrate additional indirect effects; however, it did moderate the strength of
      indirect effects of fear. CONCLUSION: This preliminary modelling suggests complex
      interactions exist between pain-related fear and pain sensitivity measures that
      further explain individual differences in behaviour.

PMID- 24890101
TI  - Insufficient efforts to boost maternal health.

PMID- 24890099
TI  - Glial cells suppress postencephalitic CD8+ T lymphocytes through PD-L1.
AB  - Engagement of the programmed death (PD)-1 receptor on activated cells by its
      ligand (PD-L1) is a mechanism for suppression of activated T-lymphocytes.
      Microglia, the resident inflammatory cells of the brain, are important for
      pathogen detection and initiation of innate immunity, however, a novel role for
      these cells as immune regulators has also emerged. PD-L1 on microglia has been
      shown to negatively regulate T-cell activation in models of multiple sclerosis
      and acute viral encephalitis. In this study, we investigated the role of glial
      cell PD-L1 in controlling encephalitogenic CD8(+) T-lymphocytes, which infiltrate
      the brain to manage viral infection, but remain to produce chronic
      neuroinflammation. Using a model of chronic neuroinflammation following murine
      cytomegalovirus (MCMV)-induced encephalitis, we found that CD8(+) T-cells
      persisting within the brain expressed PD-1. Conversely, activated microglia
      expressed PD-L1. In vitro, primary murine microglia, which express low basal
      levels of PD-L1, upregulated the co-inhibitory ligand on IFN-gamma-treatment.
      Blockade of the PD-1: PD-L1 pathway in microglial: CD8(+) T-cell co-cultures
      increased T-cell IFN-gamma and interleukin (IL)-2 production. We observed a
      similar phenomenon following blockade of this co-inhibitory pathway in astrocyte:
      CD8(+) T-cell co-cultures. Using ex vivo cultures of brain leukocytes, including
      microglia and CD8(+) T-cells, obtained from mice with MCMV-induced chronic
      neuroinflammation, we found that neutralization of either PD-1 or PD-L1 increased
      IFN-gamma production from virus-specific CD8(+) T-cells stimulated with MCMV
      IE1168-176 peptide. These data demonstrate that microglia and astrocytes control
      antiviral T-cell responses and suggest a therapeutic potential of PD1: PD-L1
      modulation to manage the deleterious consequences of uncontrolled
      neuroinflammation.

PMID- 24890102
TI  - Physician burnout: who will protect us from ourselves?

PMID- 24890103
TI  - A 28-year-old man with acute chest pain.

PMID- 24890106
TI  - Feds to scrutinize health disparities.

PMID- 24890104
TI  - Validity of the diagnostic criteria for chronic cerebrospinal venous
      insufficiency and association with multiple sclerosis.
AB  - BACKGROUND: The chronic cerebrospinal venous insufficiency theory proposes that
      altered cerebral venous hemodynamics play a role in the pathophysiology of
      multiple sclerosis. We aimed to explore the validity of this hypothesis by
      assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency
      in persons with and without multiple sclerosis. METHODS: We compared the
      proportion of venous outflow abnormalities between patients with multiple
      sclerosis and healthy controls using extracranial Doppler ultrasonography and
      gadolinium-enhanced magnetic resonance venography. Interpreting radiologists were
      blinded to the clinical status of participants. RESULTS: We enrolled 120 patients
      with multiple sclerosis and 60 healthy controls. High proportions of both
      patients (67/115 [58%]) and controls (38/60 [63%]) met 1 or more of the proposed
      ultrasound criteria for diagnosis of chronic cerebrospinal venous insufficiency
      (p = 0.6). A minority of patients (23/115 [20%]) and controls (6/60 [10%])
      fulfilled 2 or more of the proposed criteria (p = 0.1). There were no differences
      between patients and controls in the prevalence of each individual ultrasound
      criterion. Similarly, there were no differences in intracranial or extracranial
      venous patency between groups, as measured by magnetic resonance venography.
      INTERPRETATION: We detected no differences in the proportion of venous outflow
      abnormalities between patients with multiple sclerosis and healthy controls.
      Moreover, our study revealed significant methodologic concerns regarding the
      proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that
      challenge their validity.

PMID- 24890107
TI  - Condoms for sex work: protection or evidence?

PMID- 24890108
TI  - Decriminalize drugs and use public health.

PMID- 24890109
TI  - High risk of traffic crashes in pregnancy: are there any explanations?

PMID- 24890110
TI  - Healthy cities and public health news.

PMID- 24890111
TI  - 10 health stories that mattered: May 26-30.

PMID- 24890112
TI  - Migrant workers' health rights unmet.

PMID- 24890113
TI  - Mercury bioaccumulation in dragonflies (Odonata: Anisoptera): examination of life
      stages and body regions.
AB  - Dragonflies (Odonata: Anisoptera) are an important component of both aquatic and
      terrestrial food webs and are vectors for methylmercury (MeHg) biomagnification.
      Variations in mercury content with life stage and body regions may affect the
      relative transfer of mercury to aquatic or terrestrial food webs; however, there
      has been little research on this subject. Also, little is known about mercury
      bioaccumulation in different body regions of dragonflies. To address these
      knowledge gaps, dragonfly naiads, adults, and exuviae were collected at 2 lakes
      in Kejimkujik National Park, Nova Scotia, Canada, and mercury concentrations in
      different life stages and body regions were quantified. Mean whole body
      concentrations of MeHg were substantial in naiads (232 +/- 112 ng g(-1) dry wt, n
      = 66), emerging adults (236 +/- 50 ng g(-1) dry wt, n = 10), and mature adults
      (231 +/- 74 ng g(-1) dry wt, n = 20). Mean MeHg concentrations in exuviae (5.6 +/
      4.3 ng g(-1), n = 32) were 40-fold lower than in naiads and adults. Emerging
      adults had 2-fold to 2.5-fold higher Hg(II) concentrations than naiads, mature
      adults, and exuviae. In body regions of both naiads and adults, some abdomens
      contained significantly higher concentrations of Hg(II) than heads or thoraces,
      and this trend was consistent across families. Across families, Aeshnidae had
      significantly higher concentrations of MeHg and total Hg than Gomphidae and
      Libellulidae, but not higher than Cordulidae. The Hg(II) concentrations were
      lower in Aeshnidae and Libellulidae than in Gomphidae and Cordulidae. Shedding of
      exuviae presents a possible mechanism for mercury detoxification, but mercury
      concentrations and burdens in exuviae are low in comparison with naiads and
      adults. Dragonfly adults retain a high potential for transferring substantial
      amounts of MeHg to their predators.

PMID- 24890114
TI  - Time heals all wounds--but 12-HHT is faster.

PMID- 24890115
TI  - Engineering adjuvants for predictable immunity.

PMID- 24890116
TI  - Microbial hijacking of mammalian iron shuttling.

PMID- 24890117
TI  - Pioglitazone inhibits the expression of matrix metalloproteinase-9, a protein
      involved in diabetes-associated wound healing.
AB  - Matrix metalloproteinase-9 (MMP-9) is a protein involved in diabetes-associated
      wound healing. The present study aimed to determine whether pioglitazone, an
      agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma),
      inhibits the expression of MMP-9. HaCaT cells at a density of 6x105 cells/well
      were seeded into 6-well plates in medium and were cultured for 24 h. The cells
      were then treated with bovine serum albumin (BSA) only or advanced glycation end
      product (AGE)-BSA (50, 100, 200, 300 or 400 ug/ml), with or without pioglitazone
      (0.5 or 1 uM). The effects of AGE-BSA on cell viability were determined by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of
      MMP-9 secreted into the medium were detected by an enzyme-linked immunosorbent
      assay. The mRNA and protein levels were analyzed by quantitative polymerase chain
      reaction (qPCR) and western blot analysis, respectively. AGEs are able to
      increase the level of MMP-9 mRNA in HaCaT cells and the levels of MMP-9 protein
      secreted into the medium. Pioglitazone (0.5 or 1 uMU) significantly inhibited the
      levels of MMP-9 in the treated HaCaT cells. Pioglitazone (0.5 or 1 uMU) also
      suppressed the levels of MMP-9 in the cell culture medium. Pioglitazone at
      concentrations of 0.5 and 1 uMU significantly suppressed the levels of MMP-9 mRNA
      to 20 or 8%, respectively. These results suggest that pioglitazone is able to
      effectively suppress the expression of MMP-9 via a transcriptional mechanism. 

PMID- 24890119
TI  - Blueberry muffin baby associated with bone demineralization due to congenital
      transient neonatal hyperparathyroidism.

PMID- 24890118
TI  - Contrasting influences of Drosophila white/mini-white on ethanol sensitivity in
      two different behavioral assays.
AB  - BACKGROUND: The fruit fly Drosophila melanogaster has been used extensively to
      investigate genetic mechanisms of ethanol (EtOH)-related behaviors. Many past
      studies in flies, including studies from our laboratory, have manipulated gene
      expression using transposons carrying the genetic-phenotypic marker mini
      white(mini-w), a derivative of the endogenous gene white(w). Whether the mini-w
      transgenic marker or the endogenous w gene influences behavioral responses to
      acute EtOH exposure in flies has not been systematically investigated. METHODS:
      We manipulated mini-w and w expression via (i) transposons marked with mini-w,
      (ii) RNAi against mini-w and w, and (iii) a null allele of w. We assessed EtOH
      sensitivity and tolerance using a previously described eRING assay (based on
      climbing in the presence of EtOH) and an assay based on EtOH-induced sedation.
      RESULTS: In eRING assays, EtOH-induced impairment of climbing correlated
      inversely with expression of the mini-w marker from a series of transposon
      insertions. Additionally, flies harboring a null allele of w or flies with RNAi
      mediated knockdown of mini-w were significantly more sensitive to EtOH in eRING
      assays than controls expressing endogenous w or the mini-w marker. In contrast,
      EtOH sensitivity and rapid tolerance measured in the EtOH sedation assay were not
      affected by decreased expression of mini-w or endogenous w in flies. CONCLUSIONS:
      EtOH sensitivity measured in the eRING assay is noticeably influenced by w and
      mini-w, making eRING problematic for studies on EtOH-related behavior in
      Drosophila using transgenes marked with mini-w. In contrast, the EtOH sensitivity
      assay described here is a suitable behavioral paradigm for studies on EtOH
      sensitivity and rapid tolerance in Drosophila including those that use widely
      available transgenes marked with mini-w.

PMID- 24890120
TI  - Survival of larvivorous fish used for biological control of Aedes aegypti
      (Diptera: Culicidae) combined with different larvicides.
AB  - OBJECTIVE: To evaluate combinations of larvicides and fish which are predators of
      larvae of Aedes aegypti, namely Betta splendens, Trichogaster trichopterus and
      Poecilia reticulata. METHODS: We used 15 water tanks with a capacity of 250
      litres of water. In 10 tanks, larvicide - Temephos, Bti and Novaluron - was
      added, the other five contained only one specimen of fish and unchlorinated
      water. The fish were monitored for a week without changing the water, and their
      survival recorded on a form. An estimate of the Kaplan-Meier survival was
      performed to determine the significance of the tests. RESULTS: Betta splendens
      showed the lowest mortality range of larvicides tested. CONCLUSION: Combined use
      of larvivorous fish and larvicides in large water tanks is feasible.

PMID- 24890121
TI  - Metabonomic study of biochemical changes in urinary of type 2 diabetes mellitus
      patients after the treatment of sulfonylurea antidiabetic drugs based on ultra
      performance liquid chromatography/mass spectrometry.
AB  - A metabonomic study on biochemical changes in the urine of type 2 diabetes
      mellitus (T2DM) patients after the treatment of sulfonylurea (SU) antidiabetic
      drugs was performed. An ultra-performance liquid chromatography/mass spectrometry
      (UPLC/MS) method was used to generate metabolic fingerprints for the metabonomic
      analysis of urinary samples obtained from 20 T2DM patients without any drug
      treatment and 20 T2DM patients treated with SU antidiabetic drugs and 20 normal
      glucose tolerance subjects. The resulting data were subjected to chemometric
      analysis (principal component analysis and partial least squares discriminant
      analysis) to investigate the effect of SU antidiabetic drugs on urinary
      metabolite profiles of T2DM patients. Biomarkers such as xanthine, phenylalanine,
      tryptophan, hippurate, phenylacetylglutamine, carnitine C8:1, carnitine C10:3,
      uric acid and citrate were found to be responsible for the separation of T2DM and
      SU-treated groups, which indicates a potential effect of SU on energy metabolism,
      Tricarboxylic acid (TCA) cycle, gut microflora metabolism and oxidative stress.
      The study may be helpful to the understanding of the action of mechanism of SU
      antidiabetic drugs.

PMID- 24890122
TI  - Health literacy issues surrounding weight management among African American
      women: a mixed methods study.
AB  - BACKGROUND: Individuals with limited health literacy (LHL) have poorer health
      outcomes and have difficulty understanding and complying with recommendations to
      maintain a healthy lifestyle. The present study examined the association between
      health literacy (HL) and sources of dieting information, the weight-loss methods
      used and the information needed to manage weight among African American women.
      METHODS: This mixed method study included seven focus groups and a survey of 413
      African American women. Binary logistic regression analyses were performed to
      examine the association between HL category and sources of dieting information,
      weight-loss methods and information needed to lose weight. Thematic analysis was
      used to analyse focus group data. RESULTS: Women with LHL were significantly more
      likely to have a higher body mass index (BMI) than those with AHL (P < 0.05).
      Compared to respondents with LHL, those with adequate health literacy (AHL) are
      more likely to rely on information obtained from the Internet (P < 0.001),
      although they are less likely to rely on information obtained from the television
      (P < 0.05). They also are significantly more likely to participate in physical
      activity to lose weight (P <= 0.002). In addition, women with AHL were
      significantly less likely to want information on portion control (P = 0.002).
      Major qualitative themes were the importance of television and the Internet as
      major sources of health information, the use of healthy and unhealthy weight-loss
      methods, and being overwhelmed by the plethora of dieting information.
      CONCLUSIONS: HL may affect BMI among AA women, where they access dieting
      information and the types of information needed to manage their weight.

PMID- 24890123
TI  - 'You likes your way, we got our own way': Gypsies and Travellers' views on infant
      feeding and health professional support.
AB  - BACKGROUND: Gypsies and Travellers are known to have poor health status and
      access to health services, even in comparison with other ethnic minority groups.
      People from this stigmatized ethnic group are rarely consulted about their health
      needs or health service provision. Optimal infant feeding in the first year of
      life has the potential to improve lifelong health. OBJECTIVE: The aim of this
      study was to explore mothers and grandmothers' views on feeding in the first year
      of life, including the support provided by health professionals. METHODS: Semi
      structured interviews were conducted with a purposively selected sample of 22
      mothers and grandmothers of English Gypsy, Irish Traveller and Romanian Roma
      ethnicity between November 2011 and February 2012 in a city in south-west
      England. RESULTS: Few women perceived themselves as requiring help from health
      professionals in infant feeding, as acceptable and accessible support was
      available from within their own communities. Roma mothers described a tradition
      of breast-feeding and appropriately timed weaning, while English Gypsies and
      Irish Travellers customarily practised less healthy infant feeding. When mothers
      requested support, health service provision was often found inadequate.
      CONCLUSION: Exploring the views of Gypsies and Travellers is important to gain
      insight into the provision of health services for this marginalized ethnic group.
      This study has implications for policy and the practice of health professionals,
      in indicating the customary feeding behaviours of some Gypsy and Travellers, and
      highlighting areas meriting culturally sensitive health promotion.

PMID- 24890124
TI  - Diagnostic yield of transbronchial cryobiopsy in interstitial lung disease: a
      randomized trial.
AB  - BACKGROUND AND OBJECTIVE: Transbronchial lung biopsy (TBLB) is required for
      evaluation in selected patients with interstitial lung disease (ILD). The
      diagnostic yield of histopathologic assessment is variable and is influenced by
      factors such as the size of samples and the presence of crush artefacts left by
      conventional biopsy forceps. We compared the diagnostic yield and safety of TBLB
      with cryoprobe sampling versus conventional forceps sampling. METHODS: This
      randomized clinical trial analysed data for 77 patients undergoing TBLB for
      evaluation of ILD; patients were assigned to either a conventional-forceps group
      or a cryoprobe group. Two pathologists assessed the tissue samples and agreed on
      histopathologic diagnoses. We also compared the duration of procedures,
      complications and sample-quality variables. RESULTS: The most frequent diagnosis
      observed in the cryoprobe group was non-specific interstitial pneumonia.
      Histopathologic diagnoses were identified in more cases in the cryoprobe group
      (74.4%) than in the conventional-forceps group (34.1%) (P < 0.001), and the
      diagnostic yield was higher in the cryoprobe group (51.3% vs 29.1% in the
      conventional forceps group; P = 0.038). A larger mean area of tissue was
      harvested by cryoprobe (14.7 +/- 11 mm(2) ) than by conventional forceps (3.3 +/-
      4.1 mm(2)) (P < 0.001). More grade 2 bleeding (not statistically significant)
      occurred in the cryoprobe group (56.4%) than in the conventional-forceps group
      (34.2%). No differences in other complications were observed. CONCLUSIONS: TBLB
      by cryoprobe is safe and potentially useful in the diagnosis of ILD. Larger
      multisite randomized trials are required to confirm the potential benefits of
      this procedure. Clinical trial registration at ClinicalTrials.gov: NCT01064609.

PMID- 24890125
TI  - Loss of the novel tumour suppressor and polarity gene Trim62 (Dear1) synergizes
      with oncogenic Ras in invasive lung cancer.
AB  - Deregulation of cell polarity proteins has been linked to the processes of
      invasion and metastasis. TRIM62 is a regulator of cell polarity and a tumour
      suppressor in breast cancer. Here, we demonstrate that human non-small cell lung
      cancer lesions show a step-wise loss of TRIM62 levels during disease progression,
      which was associated with poor clinical outcomes. To directly examine the role of
      Trim62 in development of lung cancer, we deleted Trim62 in a mutant K-Ras mouse
      model of lung cancer. In this context, haploinsufficiency of Trim62 synergized
      with a K-RasG12D mutation to promote invasiveness and disrupt three-dimensional
      morphogenesis, both of which are associated with epithelial-mesenchymal
      transitions. Re-expression of Trim62 reverted these phenotypes in tumour cell
      lines. Thus, Trim62 loss cooperates with K-Ras mutation in tumourigenesis and
      metastasis in vivo, indicating that decreased levels of TRIM62 may play an
      important role in the evolution of lung cancer.

PMID- 24890126
TI  - Long-term probucol therapy continues to suppress markers of neurovascular
      inflammation in a dietary induced model of cerebral capillary dysfunction.
AB  - BACKGROUND: Probucol has been shown to prevent cerebral capillary disturbances
      characterized by blood-to-brain extravasation of plasma derived proteins and
      neurovascular inflammation in mice maintained on western-styled diets for 12
      weeks. However the effect of probucol on capillary integrity in aging models with
      capillary dysfunction is not known. METHODS: Wild-type C57BL6 mice were
      randomized to a low-fat (LF); saturated-fat (SFA); or SFA + Probucol diet for up
      to12 months of intervention. RESULTS: Mice fed the LF diet had substantially
      greater parenchymal abundance of plasma derived IgG and apo B lipoproteins at 12
      months, compared to LF mice at 3 months of intervention. Markers of neurovascular
      inflammation were also greater at 12 months in LF fed mice compared to LF mice at
      3 months. The SFA diet exacerbated the aging induced parenchymal abundance of IgG
      and of apo B lipoproteins and neurovascular inflammation at 12 months. The SFA
      effects were associated with increased production of intestinal lipoprotein
      amyloid-beta (Abeta). The co-provision of probucol with the SFA completely
      abolished heightened inflammation at 12 months. Probucol attenuated SFA-induced
      capillary permeability but had only a modest inhibitory effect on parenchymal
      retention of apoB lipoproteins. The improvements in markers of inflammation and
      capillary integrity because of probucol correlated with enterocytic genesis of
      chylomicron Abeta. CONCLUSION: In this long-term feeding study, probucol
      profoundly suppressed dietary SFA induced disturbances in capillary integrity but
      had a more modest effect on age-associated changes.

PMID- 24890127
TI  - How light competition between plants affects their response to climate change.
AB  - How plants respond to climate change is of major concern, as plants will strongly
      impact future ecosystem functioning, food production and climate. Here, we
      investigated how vegetation structure and functioning may be influenced by
      predicted increases in annual temperatures and atmospheric CO2 concentration, and
      modeled the extent to which local plant-plant interactions may modify these
      effects. A canopy model was developed, which calculates photosynthesis as a
      function of light, nitrogen, temperature, CO2 and water availability, and
      considers different degrees of light competition between neighboring plants
      through canopy mixing; soybean (Glycine max) was used as a reference system. The
      model predicts increased net photosynthesis and reduced stomatal conductance and
      transpiration under atmospheric CO2 increase. When CO2 elevation is combined with
      warming, photosynthesis is increased more, but transpiration is reduced less.
      Intriguingly, when competition is considered, the optimal response shifts to
      producing larger leaf areas, but with lower stomatal conductance and associated
      vegetation transpiration than when competition is not considered. Furthermore,
      only when competition is considered are the predicted effects of elevated CO2 on
      leaf area index (LAI) well within the range of observed effects obtained by Free
      air CO2 enrichment (FACE) experiments. Together, our results illustrate how
      competition between plants may modify vegetation responses to climate change. 

PMID- 24890130
TI  - Probing nanoparticles and nanoparticle-conjugated biomolecules using time-of
      flight secondary ion mass spectrometry.
AB  - Bio-conjugated nanoparticles have emerged as novel molecular probes in nano
      biotechnology and nanomedicine and chemical analyses of their surfaces have
      become challenges. The time-of-flight (TOF) secondary ion mass spectrometry
      (SIMS) has been one of the most powerful surface characterization techniques for
      both nanoparticles and biomolecules. When combined with various nanoparticle
      based signal enhancing strategies, TOF-SIMS can probe the functionalization of
      nanoparticles as well as their locations and interactions in biological systems.
      Especially, nanoparticle-based SIMS is an attractive approach for label-free drug
      screening because signal-enhancing nanoparticles can be designed to directly
      measure the enzyme activity. The chemical-specific imaging analysis using SIMS is
      also well suited to screen nanoparticles and nanoparticle-biomolecule conjugates
      in complex environments. This review presents some recent applications of
      nanoparticle-based TOF-SIMS to the chemical analysis of complex biological
      systems.

PMID- 24890131
TI  - Quality of life and satisfaction with information after radical prostatectomy,
      radical external beam radiotherapy and postoperative radiotherapy: a long-term
      follow-up study.
AB  - AIMS AND OBJECTIVES: To assess patients' symptoms, quality of life and
      satisfaction with information three to four years after radical prostatectomy,
      radical external beam radiotherapy and postoperative radiotherapy and to analyse
      differences between treatment groups and the relationship between disease
      specific, health-related and overall quality of life and satisfaction with
      information. BACKGROUND: Radical prostate cancer treatments are associated with
      changes in quality of life. Differences between patients undergoing different
      treatments in symptoms and quality of life have been reported, but there are
      limited long-term data comparing radical prostatectomy with radical external beam
      radiotherapy and postoperative radiotherapy. DESIGN: A cross-sectional survey
      design was used. METHODS: The study sample included 143 men treated with radical
      prostatectomy and/or radical external beam radiotherapy. Quality of life was
      measured using the 12-item Short Form Health Survey and the 50-item Expanded
      Prostate Cancer Index Composite Instrument. Questions assessing overall Quality
      of life and satisfaction with information were included. Descriptive statistics
      and interference statistical methods were applied to analyse the data. RESULTS:
      Radical external beam radiotherapy was associated with less urinary incontinence
      and better urinary function. There were no differences between the groups for
      disease-specific quality of life sum scores. Sexual quality of life was reported
      very low in all groups. Disease-specific quality of life and health-related
      quality of life were associated with overall quality of life. Patients having
      undergone surgery were more satisfied with information, and there was a positive
      correlation between quality of life and patient satisfaction. CONCLUSION:
      Pretreatment information and patient education lead to better quality of life and
      satisfaction. This study indicates a need for structured, pretreatment
      information and follow-up for all men going through radical prostate cancer
      treatment. RELEVANCE TO CLINICAL PRACTICE: Long-term quality of life effects
      should be considered when planning follow-up and information for men after
      radical prostate cancer treatment. Structured and organised information/education
      may increase preparedness for symptoms and bother after the treatment, improve
      symptom management strategies and result in improved quality of life.

PMID- 24890133
TI  - alpha-Cationic phosphines: synthesis and applications.
AB  - In coordination chemistry, typical ancillary ligands are anionic or neutral
      species. Cationic ones are exceptions and, when used, the positively charged
      groups are normally attached to the periphery and not close to the donating atom.
      However, this concept article highlights a series of recent experimental, as well
      as theoretical results, suggesting that the utility in catalysis of cationic
      phosphines with no spacer between the phosphorus atom and the positively charged
      group(s) has been largely overlooked. In fact, a growing number of studies
      indicate that, because of their specific architecture, these cationic ligands
      depict excellent pi-acceptor character that can exceed that of phosphites or
      polyfluorinated phosphines. This property has been used to increase the Lewis
      acidity of the metals they coordinate. Specifically, new extreme pi-acid
      catalysts, mainly based on Pt(II) and Au(I) , have been recently prepared and
      their superior performance demonstrated along several mechanistically distinct
      transformations. In this concept article the current state of the art is
      critically assessed and possible future directions of the topic discussed. 

PMID- 24890132
TI  - Factors associated with mouthguard use and discontinuation among rugby players in
      Malaysia.
AB  - AIMS: To assess rugby players' preferences for using a mouthguard and to
      determine the factors contributing to the use and discontinuation of a
      mouthguard. METHODS: A cross-sectional study was conducted in two rugby
      tournaments from 2009 to 2010. Samples were selected by convenience sampling.
      Participants were required to complete a self-administered questionnaire, which
      inquired about awareness and pattern of mouthguard use, as well as reasons if
      discontinued. RESULTS: Completed questionnaires were returned by 456
      participants, with an estimated response rate of 77.8%. All participants were
      male (mean age = 22.73, SD = 3.98). Median duration of playing was 6 years, and
      median frequency was 6 h per week. Overall mouthguard use was low (31.1%, n =
      142), especially for custom-fitted mouthguard (1.8%, n = 8), followed by stock
      mouthguard (7.7%, n = 35). Boil-and-bite type was most commonly used (21.1%, n =
      96). Of those who wore a mouthguard before, only 28% continued using it. The
      discontinuation rate for each type was as follows: stock, 57.1% (P = 0.032); boil
      and-bite, 80.2% (P = 0.002); and custom, 37.5% (P = 0.04). Age was a significant
      factor for mouthguard use (P = 0.007, OR = 1.10, 95% CI = 1.03-1.17). Breathing
      disturbance (OR = 3.36, 95% CI = 1.17-9.72) and general discomfort (OR = 3.71,
      95% CI = 1.68-8.20) were significant factors in discontinuing mouthguard use.
      CONCLUSIONS: The use of mouthguard was low among rugby players. Custom-made was
      the least worn type, possibly due to limited availability. The use of mouthguard
      increased slightly with age but was discouraged by breathing interference and
      general discomfort. Therefore, preventive effort should focus on early education
      and reinforcement, as well as on the improvement of wearability and
      accessibility.

PMID- 24890134
TI  - Overlapping allograft for primary or salvage bone tumor reconstruction.
AB  - BACKGROUND: Compared with end-to-end allograft coaptation, overlapping allograft
      offer a superior union rate by increasing the contact area. However, reports on
      overlapping allograft are scarce. Therefore, we attempted to confirm the
      usefulness of this technique either after primary tumor resection or in salvaging
      a failed reconstruction. METHODS: We analyzed the outcome of 35 overlapping
      allografts reconstructions. Indications were primary reconstruction of a skeletal
      defect (n = 19) and salvage of a failed reconstruction (n = 16). Graft survival,
      union rate, and time to union were evaluated as a function of clinical variables
      such as age, use of chemotherapy, type of junction, method of fixation, length of
      overlapped bone, and method of overlapping. RESULTS: All 35 overlapping
      allografts showed union at a mean of 5.6 months (range, 3-14 months). One
      allograft was removed with local recurrence at 19 months post-operatively.
      Average length of overlapped bone was 3.5 cm (range, 1.4-6.5 cm). Patient age <15
      years (P = 0.001) and circumferential overlapping (P = 0.011) shortened the time
      to union. CONCLUSIONS: In terms of graft failure rate, union rate, and time to
      union, overlapping allograft is an excellent technique, which overcomes the
      limitations of end-to-end fixation.

PMID- 24890135
TI  - A novel cleaning process for industrial production of xylose in pilot scale from
      corncob by using screw-steam-explosive extruder.
AB  - Steam explosion is the most promising technology to replace conventional acid
      hydrolysis of lignocellulose for biomass pretreatment. In this paper, a new screw
      steam-explosive extruder was designed and explored for xylose production and
      lignocellulose biorefinery at the pilot scale. We investigated the effect of
      different chemicals on xylose yield in the screw-steam-explosive extrusion
      process, and the xylose production process was optimized as followings: After pre
      impregnation with sulfuric acid at 80  degrees C for 3 h, corncob was treated at
      1.55 MPa with 9 mg sulfuric acid/g dry corncob (DC) for 5.5 min, followed by
      countercurrent extraction (3 recycles), decoloration (activated carbon dosage
      0.07 g/g sugar, 75  degrees C for 40 min), and ion exchange (2 batches). Using
      this process, 3.575 kg of crystal xylose was produced from 22 kg corncob, almost
      90 % of hemicellulose was released as monomeric sugar, and only a small amount of
      by-products was released (formic acid, acetic acid, fural, 5
      hydroxymethylfurfural, and phenolic compounds were 0.17, 1.14, 0.53, 0.19, and
      1.75 g/100 g DC, respectively). All results indicated that the screw-steam
      explosive extrusion provides a more effective way to convert hemicellulose into
      xylose and could be an alternative method to traditional sulfuric acid hydrolysis
      process for lignocellulose biorefinery. 

PMID- 24890136
TI  - Evaluation of microbial fuel cell operation using algae as an oxygen supplier:
      carbon paper cathode vs. carbon brush cathode.
AB  - Microbial fuel cell (MFC) and its cathode performances were compared with use of
      carbon fiber brush and plain carbon paper cathode electrodes in algae aeration.
      The MFC having carbon fiber brush cathode exhibited a voltage of 0.21 +/- 0.01 V
      (1,000 Omega) with a cathode potential of around -0.14 +/- 0.01 V in algal
      aeration, whereas MFC with plain carbon paper cathode resulted in a voltage of
      0.06 +/- 0.005 V with a cathode potential of -0.39 +/- 0.01 V. During
      polarizations, MFC equipped with carbon fiber brush cathode showed a maximum
      power density of 30 mW/m(2), whereas the MFC equipped with plain carbon paper
      showed a power density of 4.6 mW/m(2). In algae aeration, the internal resistance
      with carbon fiber brush cathode was 804 Omega and with plain carbon paper it was
      1,210 Omega. The peak currents of MFC operation with carbon fiber brush and plain
      carbon paper cathodes were -31 mA and -850 uA, respectively. 

PMID- 24890137
TI  - Production of bioactive polysaccharides by Inonotus obliquus under submerged
      fermentation supplemented with lignocellulosic biomass and their antioxidant
      activity.
AB  - The effect of lignocellulose degradation in wheat straw, rice straw, and
      sugarcane bagasse on the accumulation and antioxidant activity of extra- (EPS)
      and intracellular polysaccharides (IPS) of Inonotus obliquus under submerged
      fermentation were first evaluated. The wheat straw, rice straw, and sugarcane
      bagasse increased the EPS accumulation by 91.4, 78.6, and 74.3 % compared with
      control, respectively. The EPS and IPS extracts from the three lignocellulose
      media had significantly higher hydroxyl radical- and 2,2-diphenyl-1
      picrylhydrazyl radical-scavenging activity than those from the control medium. Of
      the three materials, wheat straw was the most effective lignocellulose in
      enhancing the mycelia growth, accumulation and antioxidant activity of I.
      obliquus polysaccharides (PS). The carbohydrate and protein content, as well as
      the monosaccharide compositions of the EPS and IPS extracts, were correlated with
      sugar compositions and dynamic contents during fermentation of individual
      lignocellulosic materials. The enhanced accumulation of bioactive PS of cultured
      I. obliquus supplemented with rice straw, wheat straw, and bagasse was evident. 

PMID- 24890129
TI  - Climate-driven diversification and Pleistocene refugia in Philippine birds:
      evidence from phylogeographic structure and paleoenvironmental niche modeling.
AB  - Avian diversification in oceanic archipelagos is largely attributed to isolation
      across marine barriers. During glacial maxima, lowered sea levels resulted in
      repeated land connections between islands joined by shallow seas. Consequently,
      such islands are not expected to show endemism. However, if climate fluctuations
      simultaneously caused shifts in suitable environmental conditions, limiting
      populations to refugia, then occurrence on and dispersal across periodic land
      bridges are not tenable. To assess the degree to which paleoclimate barriers,
      rather than marine barriers, drove avian diversification in the Philippine
      Archipelago, we produced ecological niche models for current-day, glacial maxima,
      and interglacial climate scenarios to infer potential Pleistocene distributions
      and paleoclimate barriers. We then tested marine and paleoclimate barriers for
      correspondence to geographic patterns of population divergence, inferred from DNA
      sequences from eight codistributed bird species. In all species, deep-water
      channels corresponded to zones of genetic differentiation, but six species
      exhibited deeper divergence associated with a periodic land bridge in the
      southern Philippines. Ecological niche models for these species identified a
      common paleoclimate barrier that coincided with deep genetic structure among
      populations. Although dry land connections joined southern Philippine islands
      during low sea level stands, unfavorable environmental conditions limited
      populations within landmasses, resulting in long-term isolation and genetic
      differentiation. These results highlight the complex nature of diversification in
      archipelagos: marine barriers, changes in connectivity due to sea level change,
      and climate-induced refugia acted in concert to produce great species diversity
      and endemism in the Philippines. 

PMID- 24890138
TI  - Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines
      and glucose in persons with impaired fasting glucose or impaired glucose
      tolerance: a sub-study of the DREAM trial.
AB  - AIMS: Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce
      inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes.
      We aimed to measure these effects in people with impaired fasting glucose and/or
      impaired glucose tolerance. METHODS: After approximately 3.5 years of exposure to
      rosiglitazone 8 mg (n = 88) or placebo (n = 102), 190 DREAM trial participants
      underwent abdominal computed tomography and dual-energy X-ray absorptiometry
      scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat
      content, total fat and lean mass were calculated and changes in levels of fasting
      adipokines, free fatty acids, glucose and post-load glucose were assessed.
      RESULTS: Compared with the placebo, participants on rosiglitazone had no
      difference in lean mass, had 4.1 kg more body fat (P < 0.0001) and 31 cm(2) more
      subcutaneous abdominal adipose tissue area (P = 0.007). Only after adjusting for
      total fat, participants on rosiglitazone had 23 cm2 less visceral adipose tissue
      area (P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less
      hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0
      MUg/ml with rosiglitazone and by 0.4 MUg/ml with placebo (P < 0.0001).
      Rosiglitazone's effect on fat distribution was not independent of changes in
      adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2
      h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment
      for fat distribution or changes in adiponectin or free fatty acids. CONCLUSIONS:
      In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone
      is associated with relatively less hepatic and visceral fat, increased
      subcutaneous fat and increased adiponectin levels. These effects do not appear to
      explain the glucose-lowering effect of rosiglitazone.

PMID- 24890139
TI  - Comparison of VEGF gene silencing efficiencies of chitosan and protamine
      complexes containing shRNA.
AB  - VEGF is an angiogenic factor promoting the proliferation and migration of
      endothelial cells. Inhibition of VEGF by RNAi mechanism is one of the novel and
      the most important strategies in antiangiogenesis therapy. In this study, the
      tumor silencing efficiency of ternary complexes after addition of protamine to
      chitosan complexes containing VEGF targeting shRNA was investigated. Besides
      chitosan, protamine is an effective gene delivery material. Binary and ternary
      complexes consisting of chitosan, protamine, and shRNA were prepared to target
      VEGF, their morphology, size, and zeta potential of the complexes being measured.
      The average size of the complexes was between 173 and 284 nm and zeta potential
      was between +10 and 16 mV. In the ternary complexes, size decreased as the
      chitosan ratio increased; however, its molecular weight had no effect on the size
      of complexes. HeLa, HEK293, and MCF-7 cell lines were used for in vitro
      transfection. VEGF was assayed by ELISA. A higher silencing effect was obtained
      using ternary complexes. Transgene expression was increased by adding protamine
      to chitosan complexes. Gene inhibition values in cell lines followed the rank
      HEK293>HeLa>MCF-7. The addition of protamine to the chitosan/shRNA (VEGF)
      complexes increased the knockdown of VEGF genes in the cell lines, and no
      cytotoxicity was found after the complexes had been incorporated into the cells. 

PMID- 24890140
TI  - Microdialysis of inflammatory mediators in the skin: a review.
AB  - Skin microdialysis is an established method for in vivo sample collection from
      the extracellular fluid space. This method has been extensively used in studies
      of inflammatory reactions in the skin of animals and humans. Skin microdialysis
      consists of the implantation of semi-permeable probes into the upper dermis,
      perfusion with a physiological buffer, and the recovery of the substances that
      diffused from the skin into the perfusion fluid. Microdialysis allows the
      simultaneous assessment of the temporal variations of inflammatory mediator
      release in the skin as well as the monitoring of vascular and sensory functions.
      By the aid of this technique, potential associations can be found between
      functional changes and a variety of substances and mediators released at the site
      of interest. This allows further insights into the possible mechanisms underlying
      physiological and pathophysiological events in the skin, including cutaneous
      inflammation. This review provides a comprehensive but not exhaustive review of
      the use of microdialysis in studies of experimental and clinical inflammatory
      reactions in the skin in animals and humans. 

PMID- 24890141
TI  - KumaFix fixation for thoracolumbar burst fractures: a prospective study on
      selective consecutive patients.
AB  - BACKGROUND: Short-segment U-shaped pedicle screw fixation has been widely used to
      treat thoracolumbar burst fracture. Some studies have reported the disadvantages
      of traditional U-shaped pedicle screw, which included a relatively high rate of
      adjacent segment degeneration and screw failure, including screw pullout and
      breakage. The purpose of this study was to assess the efficacy of open reduction
      and fixation using KumaFix fixation system in treatment of thoracolumbar burst
      fractures. METHODS: From June 2011 to June 2012, 45 consecutive patients with
      thoracolumbar burst fractures were enrolled. They were randomly assigned to
      treatment with KumaFix (the treatment group, n = 23) or traditional U-shaped
      pedicle screw (the control group, n = 22). The patients were followed up
      postoperatively and were assessed with regard to radiologic and clinical
      outcomes. Radiologic outcomes were assessed mainly on the basis of Cobb angle and
      vertebral wedge angle. Clinical outcomes were evaluated mainly with use of Visual
      Analog Scale (VAS) for pain and the Oswestry Disability Index (ODI)
      Questionnaire. RESULTS: All patients were followed up from 9 to 22 months. There
      were no significant differences between the two groups with regard to
      preoperative indices. The operation time in the treatment group was significantly
      lower than that in the control group. Preoperative Cobb angles and vertebral
      wedge angles in two groups were significantly decreased after surgery, and these
      have been well maintained at the last follow-up with mild correction losses. The
      results of clinical outcome showed lower VAS and ODI scores in two groups
      compared with those preoperative, and the treatment group had greater improvement
      on the ODI compared with the control group at the last follow-up. CONCLUSIONS:
      Compared with traditional U-shaped pedicle screw, KumaFix fixation system can
      achieve gradual, controlled reduction, provide enough space for bone
      implantation, and avoid acceleration of adjacent segment degeneration. It is an
      effective and reliable technique to treat thoracolumbar burst fractures.

PMID- 24890142
TI  - Preliminary radioimmunoimaging and biodistribution of 131iodine-labeled single
      chain antibody fragment against progastrin-releasing peptide(31-98) in small cell
      lung cancer xenografts.
AB  - BACKGROUND: Monoclonal antibodies (mAbs) such as DD3, raised against progastrin
      releasing peptide(31-98) (ProGRP (31-98)) antigen, have been used to target small
      cell lung cancer (SCLC). However, as an intact mAb, DD3 is cleared slowly from
      the body, with an optimal radioimmunoimaging time of 72 hours. More recently, a
      single-chain antibody fragment has demonstrated reduced excretion time in blood
      and normal tissues and is increasingly used in diagnostic cancer research.
      Thereby, it potentially increases the radioimmunoimaging efficacy. However, there
      have been few studies with this antibody fragment. The aim of this study was to
      characterize the preliminary radioimmunoimaging and biodistribution of (131)I
      anti-ProGRP(31-98) scFv in nude mice bearing SCLC xenografts. METHODS: Anti
      ProGRP(31-98) scFv was used to detect ProGRP expression by flow cytometry
      analysis and immunohistochemistry. (131)I-anti-ProGRP(31-98) scFv was injected
      intravenously into healthy Kunming mice and the percentage injected dose per gram
      (%ID/g) in various organs was calculated. Similarly, the %ID/g and tumor/non
      tumor ratio in xenograft-bearing mice was calculated. After injection of (131)I
      anti-ProGRP(31-98) scFv, treated mice were imaged at 1, 24, and 30 hours. Then
      the tumor/base ratios were calculated. RESULTS: ProGRP was highly expressed in
      NCI-H446 cells and xenograft tissue. The metabolism of (131)I-anti-ProGRP(31-98)
      scFv in healthy mice was consistent with a first-order and two-compartment model;
      T1/2alpha and T1/2beta were 10.2 minutes and 5 hours 18 minutes, respectively.
      The %ID/g of (131)I-anti-ProGRP(31-98) scFv in xenografts was much higher than in
      healthy tissues at 12 hours after injection, reaching a maximum of (5.38+/-0.92)
      %ID/g at 24 hours. Successful imaging of xenograft tissue was achieved as early
      as 1 hour post-injection and persisted until 30 hours, with 24 hours proving
      optimal. CONCLUSION: (131)I-anti-ProGRP(31-98) scFv shows highly selective tumor
      uptake with low accumulation in normal tissues and rapid blood clearance,
      indicating that it could be a promising agent for SCLC radioimmunoimaging.

PMID- 24890143
TI  - BRCA2 promoter polymorphism is associated with breast cancer prognosis in Chinese
      women.
AB  - BACKGROUND: Breast cancer 2 (BRCA2) is an important breast cancer-susceptibility
      gene. Promoter polymorphisms in BRCA2 may affect its transcription and be
      associated with cancer prognosis. METHODS: We identified five polymorphisms of
      the BRCA2 promoter region by in silico searching and direct sequencing: -254A/G
      (rs3092989), -908A/G (rs206117), -1134A/G (rs206115), -1144C/T (rs206116), and 
      1260CTTAGA/- (rs3072036). The -908A/G, -1134A/G, -1144C/T, and -1260CTTAGA/-
      polymorphisms were genotyped by direct sequencing in 491 breast cancer patients,
      and the -254A/G polymorphism was genotyped by Sequenom. RESULTS: The -1144C/T
      polymorphism was associated with clinical outcome. Carriers of the TT genotype
      had longer disease-free intervals (DFIs, P = 0.029), especially among patients
      with sporadic unilateral breast cancer (P = 0.010). Linkage disequilibrium (LD)
      analysis showed that all the five single nucleotide polymorphisms (SNPs) were in
      LD (D' > 0.8). Carriers of haplotypes containing the -1144T allele showed longer
      DFIs (P = 0.049), and the result was more significant in patients with sporadic
      unilateral cancer (P = 0.018). There were no significant associations between the
      other polymorphisms and DFI. CONCLUSIONS: The results of this study suggest that
      homozygosity for the BRCA2 T(-1144) allele is associated with a longer DFI in
      Chinese women with breast cancer. Further functional studies are warranted to
      clarify this relationship.

PMID- 24890144
TI  - Combined action of C-reactive protein and lipid profiles on risk of hypertension
      and prehypertension in Mongolian adults in Inner Mongolia, China.
AB  - BACKGROUND: Many studies have suggested that C-reactive protein (CRP) and blood
      lipids are associated with hypertension and cardiovascular disease (CVD).
      However, few studies discussed the combined action of CRP and blood lipids on the
      risk of hypertension and prehypertension. This study aimed to investigate the
      combined action of CRP and lipid profiles on the risk of hypertension and
      prehypertension in Mongolian adults from Inner Mongolia, China. METHODS: The
      systolic and diastolic blood pressure, height, weight and waist circumference
      were measured and factors such as smoking, alcohol intake, family history of
      hypertension, etc., were investigated and CRP, low-density lipoprotein
      cholesterol (LDL-C), triglycerides (TG) were tested for 2 534 Mongolian adults
      aged >= 20 years. The subjects were divided into four subgroups, namely CRP
      <median and LDL-C (TG) <median subgroup, CRP <median and LDL-C (TG) >median
      subgroup, CRP >median and LDL-C (TG) <median subgroup and CRP >median and LDL-C
      (TG) >median subgroup. The ORs (95% CIs) of hypertension and prehypertension for
      the subgroups were calculated by univariate and multivariate analysis. RESULTS:
      The multivariate adjusted ORs (95%CIs) of hypertension/prehypertension were 1.389
      (0.979-1.970)/1.151(0.865-1.531), 1.666 (1.159-2.394)/1.431 (1.060-1.930), 1.756
      (1.242-2.484)/ 1.770 (1.321-2.372), for CRP <median and LDL-C >median subgroup,
      CRP >median and LDL-C <median subgroup, and CRP >median and LDL-C >median
      subgroup, respectively, compared with CRP <median and LDL-C <median subgroup.
      Similarly, the multivariate adjusted ORs (95% CIs) of
      hypertension/prehypertension were 2.032 (1.394-2.963)/1.442 (1.047-1.988), 1.412
      (0.960-2.079)/1.596 (1.166-2.184), and 2.197 (1.595-3.027)/1.730 (1.321-2.266)
      for CRP <median and TG >median subgroup, CRP >median and TG <median subgroup, and
      CRP >median and TG >median subgroup, respectively, compared with CRP <median and
      TG <median subgroup. The risks of hypertension and prehypertension were the
      highest in the CRP >median and LDL-C (TG) >median subgroup among the four
      subgroups. CONCLUSIONS: Subjects with both CRP >median and LDL-C (TG) >median had
      highest risks of hypertension and prehypertension among all subjects. This study
      appeared to indicate that the combined action of elevated CRP and elevated LDL-C
      (TG) further increase the risks of hypertension and prehypertension among
      Mongolian population.

PMID- 24890145
TI  - Overexpression of SIRT1 is a poor prognostic factor for advanced colorectal
      cancer.
AB  - BACKGROUND: Sirtuin 1 (SIRT1) has been reported to have diverse roles in various
      biological processes through deacetylation of histone and nonhistone proteins.
      However, the correlations among SIRT1 protein expression, clinicopathological
      parameters, and survival of colorectal cancer patients remain unclear. METHODS:
      SIRT1 protein expression was measured by immunohistochemistry in a paraffin
      embedded tissue microarray, including 120 paired colorectal cancer and normal
      mucosa tissues. The correlations among SIRT1 protein expression,
      clinicopathological features, and prognosis were analyzed. RESULTS: All samples
      (100%) were positive for SIRT1, with variable staining in the cytoplasm rather
      than in the nucleus. There was significant difference in SIRT1 overexpression
      between adenocarcinomas and normal mucosal tissue (P < 0.01, chi(2) test). SIRT1
      overexpression was more frequently observed in advanced-stage tumors (P = 0.046,
      0.002, chi(2) test). SIRT1 overexpression was significantly correlated with poor
      overall survival (P = 0.013, log-rank test) and diseasefree survival (P = 0.012,
      log-rank test). CONCLUSIONS: SIRT1 overexpression correlated with advanced stage
      and poor prognosis. SIRT1 may play an important role in the progression of
      colorectal cancer.

PMID- 24890147
TI  - Evaluation of asthma control: a questionnaire-based survey in China.
AB  - BACKGROUND: Little is known about asthma control and perception of asthma among
      asthmatic patients in China. This study marked the first survey conducted on a
      national scale that aimed at obtaining baseline information on asthma control and
      patients' perception of asthma and providing a point of reference for future
      studies. METHODS: This face-to-face, questionnaire-based survey was conducted
      from April 2007 to March 2008 with 3 069 asthmatic patients from the respiratory
      outpatient clinics of 36 general hospitals located in 10 geographically dispersed
      cities. RESULTS: Consistent with the Global Initiative for Asthma (GINA)
      guidelines, 28.7% and 45.0% of our patients achieved control and partial control,
      respectively. Of the patients in the study, only 21.8% had used a peak flow meter
      (PFM), and 6.6% of these patients used it daily. Inhaled corticosteroids (ICS)
      plus a long-acting beta2 agonist (LABA) and ICS were the two most common
      medication regimens and were used in 45.6% and 30.4% of patients, respectively.
      Asthma had a significant effect on the patients' life and work. A considerable
      number of hospitalizations, emergency department visits, and sick days were
      observed. CONCLUSION: Despite improvements in asthma control and ICS and PFM
      compliance compared with past literature, the current level of asthma control
      countrywide continues to fall short of the goals set in the GINA.

PMID- 24890146
TI  - Correlation of D-dimer level with the radiological severity indexes of pulmonary
      embolism on computed tomography pulmonary angiography.
AB  - BACKGROUND: It is known that the main role of D-dimer has been as an exclusionary
      test in patients with suspected venous thromboembolism. However, the D-dimer is
      increasingly beginning to find clinical utility as a marker in the evaluation of
      the extent of the embolic disease. The aim of the study was to determine whether
      D-dimer levels predict the radiological markers of pulmonary embolism (PE)
      severity using Mastora score. METHODS: This prospective study involved 69
      patients with acute PE proved by computed tomography pulmonary angiography
      (CTPA). The D-dimer level was noted. A pulmonary artery obstruction index (PAOI;
      Mastora score) >= 21.3% indicated severe obstruction of PE. A right
      ventricle/left ventricle (RV/LV) ratio >0.9 indicated RV dysfunction. RESULTS:
      The median D-dimer level and PAOI were 765 ug/L (95% CI: 750-1 205 ug/L) and
      16.77% (95% CI: 16.32%-23.06%), respectively. The D-dimer level was positively
      correlated with PAOI (r = 0.417, P < 0.000 1). PAOI >= 21.3% was associated with
      high D-dimer levels (median, 993 ug/L (95% CI: 856-1 841 ug/L), Z = -2.991, P =
      0.003). The D-dimer level was correlated with the RV/LV ratio (r = 0.272, P =
      0.024). RV/LV ratios >0.9 were associated with high D-dimer levels (median, 880
      ug/L (95% CI: 764-1 360 ug/L), Z = -2.070, P = 0.038). PAOI was positively
      correlated with the RV/LV ratio (r = 0.390, P = 0.001). After three months, both
      the PAOI and D-dimer levels decreased (Z = -7.009, P < 0.000 1; Z = -6.976, P <
      0.000 1, respectively). CONCLUSION: D-dimer levels are positively correlated with
      PE burden and right ventricle dysfunction on CTPA, and can help monitor the
      therapeutic response.

PMID- 24890148
TI  - Decompression alone versus decompression with instrumented fusion for young
      patients with single-level lumbar disc herniation: a short-term prospective
      comparative study.
AB  - BACKGROUND: For young patients, the surgical method for lumbar disc herniation
      remains controversial. The aim of this study was to prospectively determine the
      short-term clinical outcome after surgery for young patients with lumbar disc
      herniation. METHODS: In this prospective comparative study between April 2010 and
      August 2011, a total of 80 patients underwent primary surgery at a single level
      for lumbar disc herniation. The patients were divided into two groups:
      decompression alone and decompression with instrumented fusion. An independent
      examiner clinically evaluated the patients at preoperation and at 1, 3, 6, and 12
      months after surgery. The patients filled out the instruments for back and leg
      pain using a Visual Analog Scale (VAS), Oswestry Low Back Pain Disability
      Questionnaire (ODI), and Japanese Orthopaedic Association (JOA) scores. The
      differences between the two groups were analyzed. RESULTS: The mean age of all
      the patients at the time of surgery was 33.7 years. Of the 80 patients, 38
      patients underwent decompression alone and 42 patients underwent posterior lumbar
      interbody fusion. Increasing complexity of surgery was associated with a longer
      surgery time, greater blood loss, and a longer hospital stay after surgery. Both
      methods of surgery independently improved outcomes compared with baseline status
      based on VAS, ODI, and JOA scores (P < 0.05), and no significant differences were
      found between the two groups at most of the measuring points in time, although
      patients with decompression alone had a higher JOA score (P = 0.016) and higher
      JOA recovery rate (P = 0.010) at the 3-month follow-up. CONCLUSIONS: The short
      term results of our study showed that both methods of surgery obtained effective
      clinical outcomes, but decompression alone had some advantages (shorter surgery
      time, less blood loss, shorter hospital stay, and lower cost) compared with
      decompression with instrumented fusion. Young patients with decompression alone
      could achieve great physical function earlier.

PMID- 24890149
TI  - Computer-assisted minimally invasive spine surgery for resection of ossification
      of the ligamentum flavum in the thoracic spine.
AB  - BACKGROUND: Ossification of the ligamentum flavum (OLF) has been widely
      recognized as one of the main causes of thoracic spinal canal stenosis and
      thoracic myelopathy. Decompression is the only effective strategy for treating
      thoracic myelopathy caused by OLF. The purpose of this study was to describe the
      clinical outcomes of computer-assisted minimally invasive spine surgery (CAMISS)
      for posterior decompression in patients with thoracic myelopathy caused by OLF.
      METHODS: In all cases, the surgical procedure was performed with the assistance
      of an intraoperative three-dimensional navigation system. Decompression of the
      spinal cord was performed with a high-speed drill; the supraspinal ligaments and
      spinous process were partially preserved. The outcomes were evaluated by a
      modified Japanese Orthopedic Association (JOA) scoring system and recovery rates.
      RESULTS: The mean duration of follow-up for the 14 cases was 3.9 years. All
      patients experienced neurological recovery, the mean JOA score improving from 6.1
      points preoperatively to 8.6 points at final follow-up and the mean rate of
      recovery being 52.7% (excellent in two cases, good in eight, fair in three, and
      unchanged in one). CONCLUSION: CAMISS is a safe and effective procedure for
      resection of the OLF in the thoracic spine.

PMID- 24890150
TI  - Prostasin gene polymorphism at rs12597511 is associated with severe preeclampsia
      in Chinese Han women.
AB  - BACKGROUND: Preeclampsia, characterized by hypertension and proteinuria, is a
      multifactorial disease associated with shallow invasion of trophoblast cells and
      inadequate spiral artery remodeling. Trophoblast and tumor cells have similar
      invasion mechanism. Prostasin is closely related to tumor development, invasion
      and metastasis and influences blood pressure through activating epithelial sodium
      channel. The effect of prostasin on the pathogenesis of preeclampsia remains
      unclear. This study investigated the association of prostasin gene at rs12597511
      with severe preeclampsia. METHODS: A single nucleotide polymorphism, rs12597511,
      was tested with polymerase chain reaction and restrictionfragment length
      polymorphism analyses in 179 severe preeclampsia patients and 222 normal pregnant
      women. RESULTS: The frequencies of TC + CC genotypes were significantly higher in
      severe preeclampsia group compared with in control group (the adjusted odds ratio
      was 2.030, 95% confidence interval 1.195-3.449, P = 0.009). The C allele of
      rs12597511 was present significantly more often among women with severe
      preeclampsia (P = 0.001). Genotyping analysis showed that the C allele of
      rs12597511 could confer a risk for severe preeclampsia. CONCLUSION: The higher
      frequency of C allele of prostasin gene at rs12597511 is associated with severe
      preeclampsia.

PMID- 24890151
TI  - Retinoschisis and intravitreal ranibizumab treatment for myopic choroidal
      neovascularization.
AB  - BACKGROUND: Intravitreal ranibizumab injection is effecitve on treating myopic
      CNVs, but it could be a risk factor for developing more severe retinoschisis in
      eyes with preexisted retinoschisis and epiretinal membrane. This study aimed to
      explore the incidence and features of retinoschisis after intravitreal
      ranibizumab injection for myopic choroidal neovascularization. METHODS: Eighty
      three eyes of 81 patients with choroidal neovascularization secondary to
      pathologic myopia were treated with intravitreal ranibizumab injection. The best
      corrected visual acuity and optical coherence tomography (OCT) images were
      recorded at baseline and every month thereafter. Central retina thickness and
      maximal retina thickness were measured. The subjects were divided into three
      groups. Eleven eyes that had retinoschisis and epiretinal membrane were in group
      1, six eyes that had simple epiretinal membrane were in group 2, and 66 eyes that
      had neither retinoschisis nor epiretinal membrane were in group 3. Six
      contralateral eyes in group 1 which had retinoschisis and epiretinal membrane but
      were not treated with intravitreal ranibizumab injection were set as the control
      group. RESULTS: Seven of the 11 eyes in group 1 developed more severe
      retinoschisis, the mean maximal retinal thickness increased from (380.28 +/-
      90.13) to (467.00 +/- 70.20) um (P < 0.05). The retinoschisis of all 6 eyes of
      the control group did not aggravate. Compared with the control group, the
      aggravation ratio of retinoschisis increased significantly (P < 0.05). No new
      onset of retinoschisis took place in group 2 and group 3. CONCLUSION:
      Intravitreal ranibizumab injection may be a risk factor for aggravation of
      retinoschisis in eyes with preexisted retinoschisis and epiretinal membrane.

PMID- 24890152
TI  - Effect of prolonging interval time between coronary angiography and percutaneous
      coronary intervention on X-ray-induced DNA double-strand breaks in blood
      lymphocytes.
AB  - BACKGROUND: It is desirable to minimize the risk of adverse radiation effects
      associated with percutaneous coronary intervention. The aim of this study was to
      determine the impact of prolonging the interval between coronary angiography and
      percutaneous coronary intervention on X-ray-induced DNA double-strand breaks in
      blood lymphocytes using gamma-H2AX immunofluorescence microscopy. METHODS: Blood
      samples of eight patients were taken before the first exposure to ionizing
      radiation, 10 minutes, 20 minutes, 30 minutes, 1 hour, and 24 hours after the
      last exposure to determine the gamma-H2AX foci repair kinetics. Fifty-eight
      patients undergoing percutaneous coronary intervention were randomized to an
      intermittent radiation exposure group and a continuous radiation exposure group.
      Blood samples were taken before coronary angiography and 15 minutes after the
      last exposure. By enumerating gamma-H2AX foci, the impact of prolonging the
      interval on DNA double-strand breaks was investigated. Student t-test was used to
      compare the difference in DNA double-strand breaks between the two groups.
      RESULTS: An increase in foci was found in all patients received percutaneous
      coronary intervention. The maximum number of gamma-H2AX foci was found 10-20
      minutes after the end of the last exposure. There was no statistically
      significant difference between the two groups in gamma-H2AX foci at baseline. On
      average there were (0.79 +/- 0.15) gamma-H2AX foci induced by interventional X
      rays per lymphocyte in the continuous radiation exposure group and (0.66 +/-
      0.21) in the intermittent radiation exposure group after exposure (P < 0.05).
      CONCLUSIONS: A significant number of gamma-H2AX foci develop following the
      percutaneous coronary intervention procedures. The number of X-ray-induced DNA
      double-strand breaks may be decreased by prolonging the interval time between
      coronary angiography and percutaneous coronary intervention to 30 minutes.

PMID- 24890153
TI  - Rapid resolution of subdural hematoma after targeted epidural blood patch
      treatment in patients with spontaneous intracranial hypotension.
AB  - BACKGROUND: Subdural hematoma (SDH) is a common complication of spontaneous
      intracranial hypotension (SIH). To date, the management of SDH caused by SIH
      remains controversial. In this paper, we reviewed the clinical course of SDH in
      patients with SIH, and discuss the underlying mechanism and attributing factors
      for rapid resolution of subdural hematomas after epidural blood patch (EBP)
      surgery. METHODS: We retrospectively reviewed a cohort of seventy-eight SIH
      patients diagnosed and treated with targeted EBP in our neurology center.
      Patients who received early CT/MRI follow-up after EBP operation were included.
      RESULTS: A series of four cases of SIH complicated with SDHs were evaluated.
      Early follow-up neuroimages of these patients revealed that SDHs could be
      partially or totally absorbed just two to four days after targeted epidural blood
      patch treatment. CONCLUSION: Targeted epidural blood patch can result in rapid
      hematoma regression and good recovery in some patients with a combination of SDH
      and SIH.

PMID- 24890155
TI  - Study of preferred background luminance in watching computer screen in children.
AB  - BACKGROUND: In recent years, computers have been intensively used at home. In
      contrast to paper-based books and documents, computer screen is self-illuminated
      with larger screen-background luminance difference, which greatly induces visual
      discomfort. To compensate for that, one effective solution is to offer an
      additional background luminance. In this study, we investigated whether and to
      what extent additional background lighting is needed in looking at a computer
      display comfortably. METHODS: In this study, 60 healthy children aged from 9 to
      12 years and 58 adults aged from 21 to 39 years participated in the experiments.
      They were asked to choose their most preferred background luminance intensities
      at three screen luminance levels. The data were analyzed by Matlab (R2012b) and
      SPSS 20.0. RESULTS: Both children and adult participants selected a non-dark
      background as their comfortable lighting condition when watching a computer
      display (children: t (59) = 22.0, P < 0.01, adults: t (57) = 15.5, P < 0.01).
      Comparatively, children preferred brighter background in general ( F (1,116) =
      7.0, P < 0.01). More importantly, participants' preferred background luminance
      levels were linearly correlated with screen luminance intensities (children:
      slope = 0.97, R(2) = 0.98; adults: slope = 0.38, R(2) = 1.00). CONCLUSION: These
      results indicate that varying background luminance to maintain screen-background
      luminance ratio is beneficial to human visual comfort.

PMID- 24890154
TI  - A reappraisal of the relationship between metatarsus adductus and hallux valgus.
AB  - BACKGROUND: A causal link between the metatarsus adductus and hallux valgus is
      not clear. The aim of this study was to investigate the configurations of the
      metatarsus adductus deformity by radiological measurements and reappraise the
      relationship between hallux valgus and metatarsus adductus. METHODS: The first
      step was evaluation of the relationship between metatarsus adductus and hallux
      valgus on 143 dorsoplantar weight-bearing radiographs diagnosed as hallux valgus
      which was also known as bunions. Measurements including the hallux valgus angle
      (HVA), the intermetatarsal angle (IMA), the Kilmartin angle (KA), the tibial
      sesamoid position (TSP), and metatarsus adductus angle were taken. The metatarsus
      adductus angle is defined by Sgarlato's angle (SMA) and Engel's angle (EMA)
      respectively. RESULTS: The metatarsus adductus angle positively correlates with
      the HVA (r = 0.590, P = 0.000) and KA (r = 0.601, P = 0.000), yet negatively
      correlates with the grade of TSP, (r = -0.348, P = 0.000). Contradiction of
      diagnosis existed in 22 (22/100) subjects diagnosed as metatarsus adductus by SMA
      yet normal by EMA. In this group, the correlation between HVA and metatarsus
      adductus angle was negative (r = -0.472, P = 0.027). CONCLUSIONS: EMA and SMA
      defined metatarsus adductus by different deformity apexes. Metatarsus adductus
      configurations in that the apex of the deformity lay in either the base of
      metatarsals or tarsus. They respectively correlate positively or negatively to
      the HVA.

PMID- 24890156
TI  - Biomechanical comparison of interspinous distraction device and facet screw
      fixation system on the motion of lumbar spine: a finite element analysis.
AB  - BACKGROUND: A large amount of biomechanical and clinical evidence from previous
      studies suggest the efficiency of the two different posterior lumber non-fusion
      methods, interspinous distraction device (ISDD) and facet screw fixation system
      (FSS), but the biomechanical comparison of ISDD and FSS has not been thoroughly
      clarified. METHODS: In the current study, finite element methods were used to
      investigate the biomechanical comparison of ISDD and FSS. The range of motion
      (ROM), intradiscal pressure (IDP) and the protective effects gained by
      maintaining disc heights were evaluated. RESULTS: The ROM was similar between the
      two non-fusion methods under static standing, flexion and lateral bending. The
      FSS appeared to be more effective in resisting extension. At the implanted level
      L3/4, FSS displayed better results for maintaining and increasing posterior disc
      heights. At the L4/5 level in extension and lateral bending, FSS was better than
      ISDD, with comparable results observed in other motions. Comparing the posterior
      and lateral disc heights, FSS appeared to be more effective than ISDD. FSS also
      had a minor effect on the inferior adjacent segment than ISDD. FSS was more
      effective in reducing IDP than ISDD in extension. CONCLUSION: Through the finite
      element analysis study, it can be seen that FSS demonstrates more beneficial
      biomechanical outcomes than does ISDD, such as being more effective in resisting
      extension, maintaining and increasing lumbar disc heights and reducing the
      inferior adjacent IDP in extension.

PMID- 24890157
TI  - Difficulties in post-stroke gait improvement caused by post-stroke depression.
AB  - BACKGROUND: Depression is a common problem impeding post-stroke rehabilitation.
      Up to 70% of patients show depression symptoms during the first twelve months
      after stroke onset. However, the depression and its effect on functional recovery
      can be difficult to diagnose. The purpose of this study was to use gait analysis
      as a tool to compare the recovery after stroke in patients with and without
      depression and to assess the impact of the initiation time of rehabilitation
      after stroke onset. METHODS: One hundred and forty five consecutive patients
      after first ever stroke admitted for designed rehabilitation program within 2 to
      31 months after stroke onset participated. All patients received 4 weeks
      treatment program included comprehensive rehabilitation consisted of multipurpose
      activities 5 days a week. These included individual and group exercises,
      physiotherapy, occupational therapy and gait training. Gait analysis with Kistler
      force plates was employed to assess gait pattern symmetry before and after the
      treatment. Gait symmetry was evaluated based on seven gait parameters. Regaining
      of gait pattern symmetry was assumed as a measure of rehabilitation outcome.
      RESULTS: After rehabilitation program gait symmetry was regained in patients
      without depression. Gait asymmetry remained unchanged in patients diagnosed with
      depression. No major differences in outcome from rehabilitation were noted in
      regards to the initiation time of rehabilitation after the stroke onset.
      CONCLUSIONS: Depression limits gait recovery after stroke. The time of initiation
      of rehabilitation after stroke onset does not limit the motor recovery after
      rehabilitation program.

PMID- 24890159
TI  - Therapeutic efficacy and prognosis in the treatment of lung cancer by video
      assisted thoracoscopic surgery.

PMID- 24890158
TI  - Fibroblasts weaken the anti-tumor effect of gefitinib on co-cultured non-small
      cell lung cancer cells.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common lung malignancy
      worldwide. The metastatic potential of NSCLC cells has been shown to be
      associated with the tumor microenvironment, which consists of tumor cells,
      stroma, blood vessels, immune infiltrates and the extracellular matrix.
      Fibroblasts can produce numerous extracellular matrix molecules and growth
      factors. Gefitinib has been evaluated as a first-line treatment in selected
      patients, and it has shown favorable efficacy especially in NSCLC, but it is not
      effective for everyone. METHODS: In this study, we examined the antitumor
      activity of gefitinib on lung fibroblasts co-cultured of lung cancer cells. A
      series of co-culture experiments that employed cell counting kit-8 (CCK8),
      transwells, real-time polymerase chain reaction (RT-PCR) and Western blotting
      with HFL-1 fibroblasts and A549 human lung carcinoma cells were performed to
      learn more about tumor cell proliferation, migration and invasion; and to
      determine any change of epithelial mesenchymal transition (EMT)-associated tumor
      markers vimentin, matrix metallopro-teinase 2 (MMP2) and chemotaxis cytokines
      receptor 4 (CXCR4) mRNA levels. RESULTS: A549 cell proliferation in the presence
      of HFL-1 cells was not significantly increased compared with A549 cells alone,
      but A549 cell spheroid body formation was increased after co-culture, and
      treatment with gefitinib increased further. Our study also revealed that
      fibroblasts attenuated the lung cancer cell inhibition ratio of migration and
      invasion after gefitinib treatment in vitro. To further study this mechanism, RT
      PCR analysis showed that vimentin, MMP2 and CXCR4 mRNA levels were more highly
      expressed in the lung cancer cells after co-culture, but did not obviously
      decrease compared with the control cells following gefitinib treatment. This
      suggests the mechanism by which fibroblasts attenuate gefitinib-induced
      expression of EMT-associated tumor markers. Finally, our results demonstrated
      that co-culture with A549 lung cancer cells does not alter the cell cycle
      distribution of HFL-1 fibroblasts. Furthermore, HFL-1 fibroblasts had no effect
      on the cell cycle distribution of HFL-1 cells treated with gefitinib. CONCLUSION:
      Gefitinib has lower anti-tumor activity on A549 lung cancer cells when co
      cultured with HFL-1 fibroblasts.

PMID- 24890160
TI  - Clinical experience of surgical intervention for severe acute pancreatitis.
AB  - BACKGROUND: The controversy on the treatment strategy for severe acute
      pancreatitis (SAP) has never stopped for the past century. Even now surgical
      procedures play a decisive role in the treatment of SAP, especially in managing
      the related complications, but the rational indications, timing, and approaches
      of surgical intervention for SAP are still inconclusive. METHODS: Clinical data
      of 308 SAP patients recruited during January 2000-January 2013, including 96
      conservatively treated cases plus 212 surgically intervened cases, were
      comparatively analyzed. Based on the initial surgical intervention time, the
      surgical intervention group was split into two: early intervention group (within
      2 weeks) 103 cases, and late intervention group (after 2 weeks) 109 cases.
      RESULTS: In the conservative treatment group, the cure rate was 82.29% (79/96),
      the death rate was 13.54% (13/96), and 4 cases self-discharged, while in the
      surgical intervention group, the cure rate was 84.43% (179/212) and the death
      rate was 10.85% (23/212) with 10 cases self-discharged. The difference was of no
      statistical significance between these two groups (P > 0.05). In surgical
      intervention group, the death rate 15.53% (16/103) in the early surgical
      intervention group was higher than that of late surgical intervention group 6.42%
      (7/109), and the difference was statistically significant (P < 0.05).
      CONCLUSIONS: Both conservative treatment and surgical intervention play important
      roles in the treatment of SAP, and the indication, timing, and procedure should
      be strictly followed. Surgery earlier than 2 weeks after onset of the disease is
      not recommended in patients with necrotizing pancreatitis only when there are
      specific indications, such as multiple organ failure, which does not improve
      despite active treatment, and in those who develop abdominal compartment
      syndrome.

PMID- 24890161
TI  - Kinetics of serum HBsAg in Chinese patients with chronic HBV infection with long
      term adefovir dipivoxil treatment.
AB  - BACKGROUND: Knowledge on Hepatitis B surface antigen (HBsAg) kinetics in chronic
      hepatitis B (CHB) patients with long-term adefovir dipivoxil (ADV) treatment is
      limited. The aims of this study were to investigate HBsAg kinetics in patients
      with chronic hepatitis B virus (HBV) infection treated with long-term ADV and to
      evaluate different characteristics between patients with and without HBsAg loss.
      METHODS: We retrospectively evaluated HBsAg kinetics in 24 Chinese patients with
      chronic HBV infection who achieved continuous virologic suppression during ADV
      therapy. HBV genotype was determined at baseline. Liver biochemistry, hepatitis B
      e antigen status, serum HBV DNA, and HBsAg levels were measured at baseline, 6
      months, and once every year thereafter. RESULTS: Of these 24 patients, 3, 1, and
      20 patients were followed up for 3, 5, and 6 years, respectively. Baseline serum
      HBsAg level had a moderate correlation with baseline HBV DNA level (r = 0.52, P =
      0.01). The median rate of HBsAg reduction during the therapy period was 0.08 lg
      IU * ml(-1) * y(-1). Baseline serum HBsAg level was significantly higher than
      other time points (P ranges from 0.046 to 0.002). The HBsAg reduction rate during
      the first year was similar to that in other years (P > 0.05). The HBsAg reduction
      rate during the first year in patients with eventual HBsAg loss was significantly
      faster than that in patients without HBsAg loss (P = 0.005). CONCLUSIONS: Serum
      HBsAg levels in Chinese CHB patients receiving long-term ADV demonstrated a
      gradual reduction. Patients with eventual HBsAg loss had a significantly faster
      HBsAg reduction rate during the first year than those without HBsAg loss.

PMID- 24890162
TI  - Duration of hypertension is associated with cognitive function: a cross-sectional
      study in Chinese adults.
AB  - BACKGROUND: Hypertension (HTN) is a very prevalent public health problem and as
      the population ages, cognitive impairment (CI) is also going to be a public
      health burden. However, the relationship between hypertension duration and
      cognitive function declination worldwide is still unknown. The aim of the study
      was to investigate the effects of HTN duration on CI in Chinese population.
      METHODS: At baseline, 1 386 HTN patients and 293 normotensive (NT) people were
      enrolled. The HTN patients were further divided into four subgroups (duration of
      HTN <6 years, 6-10 years, 11-20 years, and >20 years) according to the HTN
      duration and were screened for cognitive function with neuropsychological tests
      including mini-mental-state-examination (MMSE) and clock-drawing-test (CDT) in
      comparison with the NT group. RESULTS: More HTN patients had CI (45.3%) than NT
      subjects (30.4%), and increased with HTN duration (P < 0.000 1). Compared with
      the scores of MMSE and CDT in the NT group, the declines were higher in the HTN
      patients (P < 0.000 1), and in the four HTN subgroups, both MMSE and CDT scores
      fall when the HTN duration increased (P < 0.05). Furthermore, in the HTN
      population without CI, the trend in alteration of CI was relatively mild but
      still existed (P < 0.05). CONCLUSION: People with HTN are more likely to have CI
      and the possibility and aggravation increases the prolongation of HTN duration,
      both in amnesic and nonamnesic function.

PMID- 24890163
TI  - Proliferating cell nuclear antigen involved in the repair process of ouabain
      induced brain damage independent of hypertension in rats.
AB  - BACKGROUND: Ouabain is a mammalian adrenocortical hormone that is involved in the
      pathogenesis of hypertension by inhibiting Na-K ATPase activity. It also
      participates in a variety of kinase-mediated signaling pathways associated with
      Na-K ATPase. Previous studies have shown that ouabain can cause cardiac
      remodeling independent of elevated blood pressure and that proliferating cell
      nuclear antigen (PCNA) plays a coordinating role for numerous proteins involved
      in multiple processes associated with DNA synthesis. Therefore, we hypothesized
      that ouabain might play a role in the cerebral cortex through signaling pathways
      independent of hypertension. And PCNA might be involved in this process. METHODS:
      Male Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as
      the control group. Systolic blood pressure was recorded weekly. After four weeks
      of treatment, morphological changes in the cerebral cortex were analyzed using
      light and transmission electron microscopy. The expression of PCNA in the
      cerebral cortex was evaluated by immunohistochemistry, real time quantitative
      PCR, and Western blotting. RESULTS: After 4-week treatment, there was no
      significant difference in systolic blood pressure compared with the control
      group, but both structural deterioration and up-regulated expression of PCNA in
      the brain was induced by ouabain treatment. CONCLUSIONS: These results suggest
      that ouabain induces alterations in the brain structure, and this effect is
      independent of blood pressure. PCNA might be involved in the repair process of
      ouabain-induced brain damage.

PMID- 24890164
TI  - Expression of suppressor of cytokine signaling 1 in the peripheral blood of
      patients with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse
      parenchymal disease with a poor prognosis. A variety of cytokines and chemokines
      are involved in its pathophysiology. The aim of this study was to evaluate the
      clinical features in IPF patients with the expression of suppressor of cytokine
      signaling 1 (SOCS-1), which acts as a negative regulator of cytokine signaling.
      METHODS: IPF patients (n = 20) and healthy controls (n = 16) were included in
      this study. The expression of SOCS-1 was analyzed in peripheral blood mononuclear
      cells (PBMC) of subjects using RT-PCR. Interleukin 4 (IL-4), transforming growth
      factor beta1 (TGF-beta1) and type I collagen expression were also analyzed in
      each individual using enzyme-linked immunosorbent assay (ELISA). The clinical
      characteristics of IPF patients were delineated. These results were analyzed by
      SPSS13.0 statistics software. RESULTS: SOCS-1 mRNA expression was significantly
      decreased in the PBMC of IPF patients compared with healthy controls; serum
      levels of IL-4 and TGF-beta1 were higher in IPF patients. The patients with lower
      expression of SOCS-1 developed lower percentage of forced vital capacity (FVC%)
      and DLCO/VA. A patients' SOCS-1 mRNA level was negatively correlated with serum
      levels of IL-4, and negatively correlated with their high-resolution computed
      tomography (HRCT) scores. CONCLUSIONS: SOCS-1 mRNA can be detected in PBMC, and
      it is down-regulated in IPF patients. The expression of SOCS-1 is associated with
      the severity of IPF patients' symptoms, so it might be the predictor of disease
      severity. SOCS-1 might play an important role in IPF by reducing the expression
      of the T helper type 2 (Th2) cell-related cytokine IL-4.

PMID- 24890165
TI  - Angiogenesis effect of Astragalus polysaccharide combined with endothelial
      progenitor cells therapy in diabetic male rat following experimental hind limb
      ischemia.
AB  - BACKGROUND: Diabetes mellitus (DM) is a common disease accompanied with a high
      incidence of hind limb ischemia (HLI). In recent years, numerous studies
      demonstrated that endothelial progenitor cells (EPCs) are involved in
      angiogenesis and maintenance of vascular integrity following HLI. On the other
      side, it has been proved that Astragalus polysaccharide (APS) could promote
      angiogenesis. In the present study, we aimed to evaluate the effect of APS and
      EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery
      ligation in rats with streptozotocin (STZ)-induced diabetes. METHODS: Rats (n =
      110) were randomly assigned to the following groups: sham group, ischemia group,
      APS group, EPCs group and APS+EPCs group. APS, EPCs or an equal volume of vehicle
      was administered intramuscularly after HLI induction, and 6 rats were assessed by
      angiography at 28 days after induction of HLI, 6 rats were sacrificed at the same
      time point to take histological studies, biochemical tests were also performed at
      that point in the rest rats. RESULTS: APS or EPCs treatment induced an increase,
      respectively, in the protein expression of vascular endothelial growth factor
      (VEGF) (36.61%, 61.59%), VEGF receptor-1 (VEGFR-1) (35.50%, 57.33%), VEGFR-2
      (31.75%, 41.89%), Angiopoietin-1 (Ang-1) (37.57%, 64.66%) and Tie-2 (42.55%,
      76.94%) (P < 0.05), after HLI injury. And combined therapy of APS and EPCs
      enhanced the effort of angiogenesis after HLI induction in diabetic rats, through
      elevating protein expression of VEGF (99.67%), VEGFR-1 (105.33%), VEGFR2
      (72.05%), Ang-1 (114.30%) and Tie-2 (111.87%) (P < 0.05). Similarly, mRNA
      expression of VEGF, VEGFR-1, VEGFR2, Ang-1, Tie-2 also show similar trends as
      well as protein expression (P < 0.05). CONCLUSION: APS or EPCs could enhance
      angiogenesis, and the combined treatment leads to better effort, at least,
      partially via VEGF/VEGFR and Ang-1/Tie-2 signaling pathway.

PMID- 24890166
TI  - Effects of peroxisome proliferator-activated receptor-beta/delta on sepsis
      induced acute lung injury.
AB  - BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) are the first steps in the development of multiple organ failure induced
      by sepsis. A systemic excessive inflammatory reaction is currently the accepted
      mechanism of the pathogenesis of sepsis. Several studies have suggested a
      protective role of the peroxisome proliferator activated receptor-beta/delta
      (PPAR-beta/delta) in related inflammatory diseases. But the role of
      PPARbeta/delta in ALI remains uncertain. The aim of this study was to investigate
      the role and possible mechanism of PPARbeta/delta in ALI induced by sepsis.
      METHODS: Cecal ligation and puncture (CLP) was used as a sepsis model. Rats were
      randomly divided into four groups, the control group (CON, n = 6), sham-operation
      group (SHAM, n = 12), cecal ligation and puncture group (CLP, n = 30), GW501516
      group (CLP+GW, n = 25), which underwent CLP and were subcutaneously injected with
      the PPAR-beta/delta agonist GW501516 (0.05 mg/100 g body weight). Survival was
      monitored to 24 hours after operation. Blood pressure, serum creatinine, blood
      urea nitrogen, aspartate aminotrasferase and alanine aminotrasferase were
      measured after CLP. Concentrations of tumor necrosis factor alpha (TNF-alpha) and
      interleukin (IL)-1beta in serum were detected by enzyme linked immunosorbent
      assay (ELISA) kits. Lung tissue samples were stained with H&E and scored
      according to the degree of inflammation. Bacterial colonies were counted in the
      peritoneal fluid. Alveolar macrophages were cultured and incubated with GW501516
      (0.15 umol/L) and PPARbeta/delta adenovirus and then treated with
      Lipopolysaccharide (2 ug/ml) for 2 hours. The TNF-alpha, IL-1beta and IL-6 RNA in
      lung and alveolar macrophages were determined by real-time PCR. Phosphorylation
      of signal transducer and activator of transcription 3 (STAT3) in lung and
      alveolar macrophages was detected by Western blotting. RESULTS: GW501516
      significantly increased the survival of septic rats, decreased histological
      damage of the lungs, reduced inflammatory cytokines in serum and lung tissues of
      septic rats and did not increase counts of peritoneal bacteria. In vitro,
      GW501516 and over-expression of PPARbeta/delta attenuated gene expression of TNF
      alpha, IL-1beta and IL-6 in alveolar macrophages. Both in vivo and in vitro,
      PPARbeta/delta inhibited the phosphorylation of STAT3. CONCLUSION: PPARbeta/delta
      plays a protective role in sepsis induced ALI via suppressing excessive
      inflammation.

PMID- 24890167
TI  - Reliability of pressure cuff induced transient limb ischemia in conscious
      rabbits.
AB  - BACKGROUND: The protective effects of transient limb ischemia (TLI) induced by
      several cycles of intermittent pressure cuff inflation and deflation for a period
      have been widely investigated, however the reliability of this protocol has not
      been clearly verified. Our study aimed to investigate the reliability of pressure
      cuff induced TLI in conscious rabbits. METHODS: Eight New Zealand rabbits were
      subjected to TLI without anesthesia. TLI consisted of 3 cycles of ischemia and
      reperfusion induced by inflating the cuff placed on the left lower limb to 200
      mmHg for 5 minutes followed by deflating the cuff for 5 minutes. Skin color,
      pulse oxygen saturation (SpO2), pulse rate (PR), plethysmogram waveform (Pleth),
      and ultrasound detection of the blood flow in the extremity distal to the
      ischemic segment were observed to confirm ischemia and reperfusion during TLI.
      The frequency of severe limb movement during TLI was also recorded to assess the
      amenability of this protocol in conscious rabbits. RESULTS: The skin color of the
      extremity distal to the ischemic segment changed from bright red to dark purple
      after inflating the cuff to 200 mmHg, and returned to normal after cuff
      deflation. Pleth, PR and SpO2 disappeared during ischemia and restored during
      reperfusion in the monitor. Blood flow of the left posterior tibial artery was
      completely blocked by a pressure of 200 mmHg during ischemia, and recovered
      immediately after cuff deflation. The frequency of severe limb movement in supine
      position was higher than that in prone position (P < 0.05), but there was no
      severe limb movement that could result in disturbance to ischemia when the
      rabbits were placed in prone position. CONCLUSION: Pressure cuff inflating to 200
      mmHg for 5 minutes and deflating for 5 minutes is a reliable regimen to induce
      TLI in conscious rabbits.

PMID- 24890168
TI  - Lycopene can reduce prostate-specific antigen velocity in a phase II clinical
      study in Chinese population.
AB  - BACKGROUND: Epidemiological studies have shown that lycopene has anti-prostate
      cancer effect. In vitro tests also confirmed that it can promote apoptosis of
      prostate cancer cells. We investigated the effect of whole-tomato supplement
      lycopene on the prostate-specific antigen velocity in selected prostate cancer
      patients. METHODS: Twenty selected prostate cancer patients were given whole
      tomato supplement lycopene 10 mg per day for about 6 months. Blood samples of
      patients were collected weekly to measure serum prostate-specific antigen (PSA)
      values. PSA velocity slope, which reflects the change of PSA, and the degree of
      change were also calculated. By comparing the values of average PSA velocity
      slope (rise or fall of PSA) before and after the administration of lycopene, the
      effect of lycopene can be evaluated. Blood chemistry analysis was regular
      followed as safety control. RESULTS: Three patients in the research group
      withdrew within 3 weeks because of inability to conform. The rest 17 patients
      continued for an average period of 6 months. Two patients withdrew because of
      cancer progression (PSA rise) who later received active treatment. The average
      fall in PSA was equivalent to 2.56% over (i.e. an average slope/d of -0.000 28)
      the first 3 months. In the last 3 months, average fall in PSA was equivalent to
      31.58% (i.e. an average slope/d of -0.003 51). The Wilcoxon rank-sum test showed
      a statistically significant decrease of PSA velocity slope overall (P = 0.000 9).
      Analysis of the PSA doubling time (pre- vs. post-treatment) showed a median
      increase over 3 months but this was not statistically significant (P = 0.21). No
      toxic side effect was observed during the whole process. The results indicate
      that the average PSA change is "decline" in patients, and the degree of the
      decline is accelerated. CONCLUSION: Administration of lycopene was able to reduce
      PSA velocity in this study group.

PMID- 24890169
TI  - Establishment of novel rat models for premalignant breast disease.
AB  - BACKGROUND: Breast cancer has become one of the most common malignant tumors
      among females over the past several years. Breast carcinogenesis is a continuous
      process, which is featured by the normal epithelium progressing to premalignant
      lesions and then to invasive breast cancer (IBC). Targeting premalignant lesions
      is an effective strategy to prevent breast cancer. The establishment of animal
      models is critical to study the mechanisms of breast carcinogenesis, which will
      facilitate research on breast cancer prevention and drug behaviors. In this
      study, we established a feasible chemically-induced rat model of premalignant
      breast cancer. METHODS: Following the administration of the drugs (carcinogen,
      estrogen, and progestogen) to Sprague-Dawley (SD) rats, tumors or suspicious
      tumors were identified by palpation or ultrasound imaging, and were surgically
      excised for pathological evaluation. A series of four consecutive steps were
      carried out in order to determine the carcinogen: 7,12-dimethylbenzaanthracene
      (DMBA) or 1-methyl-1-nitrosourea, the route of carcinogen administration, the
      administration period of estrogen and progestogen, and the DMBA dosage. RESULTS:
      Stable premalignant lesions can be induced in SD rats on administration of DMBA
      (15 mg/kg, administered three times) followed by administration of female
      hormones 5-day cycle. RESULTS: were confirmed by ultrasound and palpation.
      CONCLUSION: Under the premise of drug dose and cycle, DMBA combined with estrogen
      and progestogen can be used as a SD rat model for breast premalignant lesions.

PMID- 24890170
TI  - Nine-month angiographic and two-year clinical follow-up of polymer-free sirolimus
      eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery
      disease: the Nano randomized trial.
AB  - BACKGROUND: First generation drug-eluting stents (DES) were associated with a
      high incidence of late stent thrombosis (ST), mainly due to delayed healing and
      re-endothelization by the durable polymer coating. This study sought to assess
      the safety and efficacy of the Nano polymer-free sirolimus-eluting stent (SES) in
      the treatment of patients with de novo coronary artery lesions. METHODS: The Nano
      trial is the first randomized trial designed to compare the safety and efficacy
      of the Nano polymer-free SES and Partner durable-polymer SES (Lepu Medical
      Technology, Beijing, China) in the treatment of patients with de novo native
      coronary lesions. The primary endpoint was in-stent late lumen loss (LLL) at 9
      month follow-up. The secondary endpoint was major adverse cardiac events (MACE),
      a composite of cardiac death, myocardial infarction or target lesion
      revascularization. RESULTS: A total of 291 patients (Nano group: n = 143, Partner
      group: n = 148) were enrolled in this trial from 19 Chinese centers. The Nano
      polymer-free SES was non-inferior to the Partner durable-polymer DES at the
      primary endpoint of 9 months (P < 0.001). The 9-month in-segment LLL of the
      polymer-free Nano SES was comparable to the Partner SES (0.34 +/- 0.42) mm vs.
      (0.30 +/- 0.48) mm, P = 0.21). The incidence of MACE in the Nano group were 7.6%
      compared to the Partner group of 5.9% (P = 0.75) at 2 years follow-up. The
      frequency of cardiac death and stent thrombosis was low for both Nano and Partner
      SES (0.8% vs. 0.7%, 0.8% vs. 1.5%, both P = 1.00). CONCLUSIONS: In this
      multicenter randomized Nano trial, the Nano polymer-free SES showed similar
      safety and efficacy compared with the Partner SES in the treatment of patients
      with de novo coronary artery lesions. Trials in patients with complex lesions and
      longer term follow-up are necessary to confirm the clinical performance of this
      novel Nano polymer-free SES.

PMID- 24890171
TI  - Impact of biodegradable versus durable polymer drug-eluting stents on clinical
      outcomes in patients with coronary artery disease: a meta-analysis of 15
      randomized trials.
AB  - BACKGROUND: Drug eluting stents (DESs) made with biodegradable polymer have been
      developed in an attempt to improve clinical outcomes. However, the impact of
      biodegradable polymers on clinical events and stent thrombosis (ST) remains
      controversial. METHODS: We searched Medline, the Cochrane Library and other
      internet sources, without language or date restrictions for articles comparing
      clinical outcomes between biodegradable polymer DES and durable polymer DES.
      Safety endpoints were ST (definite, definite/probable), mortality, and myocardial
      infarction (MI). Efficacy endpoints were major adverse cardiac event (MACE) and
      target lesion revascularization (TLR). RESULTS: We identified 15 randomized
      controlled trials (n = 17 068) with a weighted mean follow-up of 20.6 months.
      There was no statistical difference in the incidence of definite/probable ST
      between durable polymer- and biodegradable polymer- DES; relative risk (RR) 0.83;
      95% confidence interval (CI) 0.62-1.11; P = 0.22. Biodegradable polymer DES had
      similar rates of definite ST (RR 0.94, 95% CI 0.66-1.33, P = 0.72), mortality (RR
      0.94, 95% CI 0.82-1.09, P = 0.43), MI (RR 1.08, 95% CI 0.92-1.26. P = 0.35), MACE
      (RR 0.99, 95% CI 0.91-1.09, P = 0.85), and TLR (RR, 0.94, 95% CI 0.83-1.06, P =
      0.30) compared with durable polymer DES. Based on the stratified analysis of the
      included trials, the treatment effect on definite ST was different at different
      follow-up times: <= 1 year favoring durable polymer DES and >1 year favoring
      biodegradable polymer DES. CONCLUSIONS: Biodegradable polymer DES has similar
      safety and efficacy for treating patients with coronary artery disease compared
      with durable polymer DES. Further data with longer term follow-up are warranted
      to confirm the potential benefits of biodegradable polymer DES.

PMID- 24890172
TI  - Corneal refractive surgery and phakic intraocular lens for treatment of amblyopia
      caused by high myopia or anisometropia in children.
AB  - OBJECTIVE: A systematic review of literature was performed to compare various
      visual function parameters including the final visual acuity outcome and/or
      adverse events between corneal refractive surgery (CLRS) and phakic intraocular
      lens implantation (p-IOLi) in the treatment of refractive amblyopic children.
      DATA SOURCES: Two reviewers independently searched the PubMed, EMBASE, and
      Controlled Trials Register databases for publications from 1991 to 2013. STUDY
      SELECTION: There were 25 articles, including 597 patients and 682 eyes, was
      included in CLRS group. Among them, 21 articles reported the use of CLRS in the
      treatment of myopic anisometropia for 318 patients (13 photorefractive
      keratectomy or laser epithelial keratomileusis and eight laser in situ
      keratomileusis). And 11 articles had the results of CLRS in treating hyperopic
      anisometropic amblyopia children. Eleven articles reported the effect of p-IOLi
      for treating high myopia or anisometropic amblyopia, including 61 patients (75
      eyes). Age, pre- and postoperation best-corrected vision acuity (BCVA), and
      spherical equivalent (SE) were compared in CLRS and p-IOLi groups. RESULTS: The
      average age of CLRS group and p-IOLi group has no statistically significant
      difference. The SE in CLRS group for myopic anisometropia amblyopia patients was
      (-10.13 +/- 2.73) diopters (D) and for hyperopic anisometropia amblyopia patients
      was (5.58 +/- 1.28) D. In p-IOLi group the SE was (-14.01 +/- 1.93) D. BCVA was
      improved significantly in both groups, and even better in p-IOLi group.
      Refractive errors were corrected in both groups, but there was no clinically
      significant difference in final SE between each group. More than one-half of the
      children had improved binocular fusion and stereopsis function in both groups.
      CONCLUSIONS: Both CLRS group and p-IOLi group showed their advantage in treating
      refractive amblyopia in children. In comparing p-IOLi with CLRS for treatment of
      refractive amblyopia, no statistically significant difference in final BCVA was
      observed.

PMID- 24890173
TI  - Progress of radiation oncology: known and unknown.
AB  - OBJECTIVE: To elaborate known and unknown aspects of radiation oncology. DATA
      SOURCES: Data cited in this review were obtained mainly from PubMed and Medline
      in English from 1999 to 2013, with keywords "individualized medicine",
      "personalized medicine", "radiation dose", "radiation target", "molecular
      targeted therapy", "molecular imaging" and "functional imaging". STUDY SELECTION:
      Articles regarding radiation target delineation, radiation doses, new technology
      and equipment, combination of radiotherapy and molecular targeted therapy as well
      as other aspects were identified, retrieved and reviewed. RESULTS: A larger
      radiation field and a higher radiation dose are not always better. New equipment
      and technology are also not always better than conventional equipment and
      technologies. Effectiveness of radiotherapy combined with molecular targeted
      therapy needs more data to verify. CONCLUSION: Personalized radiotherapy is the
      direction for the future.

PMID- 24890174
TI  - Metallic resurfacing hemiarthroplasty of the first metatarsophalangeal joint
      combined with first metatarsal osteotomy for the treatment of hallux rigidus with
      hallux valgus in China.

PMID- 24890175
TI  - A ten-year retrospective review of 1,107 snakebite patients in Sanya, China.

PMID- 24890176
TI  - A simple and efficient method of DNA extraction from formalin-fixed and paraffin
      embedded tissues for screening EGFR gene mutation by gene sequencing.

PMID- 24890177
TI  - Early postoperative infarction out of the middle cerebral artery distribution
      following superficial temporal artery-middle cerebral artery bypass: clinical
      features and pathogenesis.

PMID- 24890178
TI  - Anesthesia management for a patient with anti-NMDA receptor encephalitis
      undergoing ovarian tumor resection.

PMID- 24890179
TI  - Pituitary deficiency due to primary pituitary apoplexy.

PMID- 24890180
TI  - Smoking and spontaneous coronary artery dissection: coincidence or not?

PMID- 24890181
TI  - Reprint of On the link between biomagnetic monitoring and leaf-deposited dust
      load of urban trees: relationships and spatial variability of different particle
      size fractions.
AB  - Biomagnetic monitoring of urban tree leaves has proven to be a good estimator of
      ambient particulate matter. We evaluated its relevancy by determining leaf area
      normalised weight (mg m(-2)) and SIRM (A) of leaf-deposited particles within
      three different size fractions (>10 MUm, 3-10 MUm and 0.2-3 MUm) and the SIRM of
      the leaf-encapsulated particles. Results showed that throughout the in-leaf
      season, the trees accumulated on average 747 mg m(-2) of dust on their leaves, of
      which 74 mg m(-2) was within the 0.2-10 MUm (~PM10) size range and 40 mg m(-2)
      within the 0.2-3 MUm (~PM3) size range. A significant correlation between the
      SIRM and weight of the surface-deposited particles confirms the potential of
      biomagnetic monitoring as a proxy for the amount of leaf-deposited particles.
      Spatial variation of both SIRM and weight throughout the street canyon suggests
      traffic and wind as key factors for respectively the source and distribution of
      urban particulates. 

PMID- 24890182
TI  - Vascular resection during radical resection of pancreatic adenocarcinomas:
      evolution over the past 15 years.
AB  - This literature review aimed to critically analyze oncological results of
      vascular resection during pancreatectomy for adenocarcinoma in the light of the
      concept evolution of locally advanced tumors and microscopic complete resection.
      The literature search was conducted in PubMed and Medline for the period June
      1994 to December 2012, retaining English as the language of publication. The
      review of 12 publications indicated that mortality and morbidity rates were not
      significantly different for pancreatectomy with or without venous resection (VR).
      Six comparative studies showed worse long-term survival in the VR group, though
      one meta-analysis, albeit with a significant population heterogeneity,
      demonstrated that the overall survival between VR and the control group was
      similar (12% vs. 17%). The compilation of 13 comparative studies showed a
      significantly lower rate of complete microscopic resection in the VR patient
      group compared to controls (63% vs. 77%; P = 0.001). Concerning pancreatectomy
      combined to arterial resection, the literature review indicated a significantly
      greater mortality and morbidity rate and a lower survival rate compared to
      pancreatic resection alone. Conflicting results concerning the long-term outcome
      of VR was due to the heterogeneity of the patient population. Since the only
      chance to cure patients of pancreatic adenocarcinoma is to obtain free resection
      margins, VR is a valid therapeutic option. But combined arterial resection to
      pancreatic resection does not appear to be recommended. 

PMID- 24890183
TI  - Porphyrin-incorporated 2D D-A polymers with over 8.5% polymer solar cell
      efficiency.
AB  - A copolymerization strategy is developed to utilize porphyrin as a complementary
      light-harvesting unit (LHU) in D-A polymers. For polymer solar cells (PSCs), the
      presence of LHUs increases the short-circuit current density (Jsc ) without
      sacrificing the open-circuit voltage (Voc ) and fill factor (FF). Up to 8.0%
      power conversion efficiency (PCE) is delivered by PPor-2:PC71 BM single-junction
      PSCs. A PCE of 8.6% is achieved when a C-PCBSD cathodic interlayer is introduced.

PMID- 24890184
TI  - Sexual motivation, sexual transactions and sexual risk behaviors in men who have
      sex with men in Dar es Salaam, Tanzania.
AB  - Understanding the associations between sexual motivation and sexual risk
      behaviors of men who have sex with men (MSM) is critical for developing effective
      HIV prevention interventions. To examine these associations, we employed data
      from a survey of 200 MSM in Dar es Salaam, Tanzania, recruited through respondent
      driven sampling. Results showed that 44.5 % of surveyed participants most often
      looked for love/affection when having sex, and 36.5 % most often looked for
      money. Money-motivated MSM were more likely to identify themselves as bisexual,
      more likely to have anal sex, and had significantly higher numbers of partners of
      both sexes. Those who most often looked for love/affection were less likely to
      ask for condom use, to actually use a condom, and to use lubrication in anal sex.
      MSM with different sexual motivations had dissimilar sexual risk behaviors.
      Tailored health interventions for each group to reduce these sexual risks for
      STIs/HIV prevention are needed.

PMID- 24890186
TI  - Subjective word-finding difficulty reduces engagement in social leisure
      activities in Alzheimer's disease.
AB  - OBJECTIVES: To assess the influence of subjective word-finding difficulty on
      degree of engagement in social leisure activities among individuals with
      Alzheimer's disease (AD). DESIGN: Analysis of data collected from the second
      cohort of the Multicenter Study of Predictors of Disease Course in Alzheimer's
      disease. SETTING: Four study sites in the United States and France. PARTICIPANTS:
      Individuals diagnosed with mild to moderate AD (N = 236). MEASUREMENTS: On
      separate questionnaires, participants were asked to 1) report whether they had
      trouble finding the right word when speaking (subjective word-finding difficulty)
      and 2) rate their frequency and enjoyment of social and nonsocial leisure
      activities. Objective language measures included object naming and verbal
      fluency. Measures of dependence, depression, cognitive status, age, sex, and
      education were also included as covariates in regression analyses. RESULTS: Fifty
      two percent of the sample reported word-finding difficulty, and subjective
      complaints were correlated with poorer verbal fluency scores. Subjective word
      finding difficulty was selectively related to social but not nonsocial activity
      measures. Endorsers of word-finding difficulty reported less frequency and
      enjoyment of social leisure activities, controlling for effects of covariates and
      objective word-finding ability. In contrast, lower engagement in nonsocial
      activities was associated with older age and higher depression scores but not
      with word-finding complaints. Caregivers' reports of study participants'
      activities corroborated these results. CONCLUSION: Individuals with AD who are
      aware of increasing word-finding failures are less likely to participate in and
      enjoy socially oriented leisure activities. This finding may have significant
      implications for clinical and health outcomes in AD. Failure to evaluate
      subjective language complaints could result in social withdrawal symptoms,
      threatening the individual's quality of life and increasing caregiver burden.
      Reduced social interaction may ultimately exacerbate language symptoms over time.

PMID- 24890185
TI  - Riluzole suppresses postinhibitory rebound in an excitatory motor neuron of the
      medicinal leech.
AB  - Postinhibitory rebound (PIR) is an intrinsic property often exhibited by neurons
      involved in generating rhythmic motor behaviors. Cell DE-3, a dorsal excitatory
      motor neuron in the medicinal leech exhibits PIR responses that persist for
      several seconds following the offset of hyperpolarizing stimuli and are
      suppressed in reduced Na(+) solutions or by Ca(2+) channel blockers. The long
      duration and Na(+) dependence of PIR suggest a possible role for persistent Na(+)
      current (I NaP). In vertebrate neurons, the neuroprotective agent riluzole can
      produce a selective block of I NaP. This study demonstrates that riluzole
      inhibits cell DE-3 PIR in a concentration- and Ca(2+)-dependent manner. In 1.8 mM
      Ca(2+) solution, 50-100 uM riluzole selectively blocked the late phase of PIR, an
      effect similar to that of the neuromodulator serotonin. However, 200 uM riluzole
      blocked both the early and late phases of PIR. Increasing extracellular Ca(2+) to
      10 mM strengthened PIR, but high riluzole concentrations continued to suppress
      both phases of PIR. These results indicate that riluzole may suppress PIR via a
      nonspecific inhibition of Ca(2+) conductances and suggest that a Ca(2+)-activated
      nonspecific current (I(CAN)), rather than I NaP, may underlie the Na(+)-dependent
      component of PIR.

PMID- 24890187
TI  - Additive effect of polymorphisms in the beta2 -adrenoceptor and NADPH oxidase p22
      phox genes contributes to the loss of estimated glomerular filtration rate in
      Chinese.
AB  - Because increased oxidative stress may mediate the detrimental actions of
      enhanced sympathetic nervous activity on renal function and vice versa, we
      investigated the effect of the polymorphic Arg16Gly in the beta2 -adrenoceptor
      (ADRB2) gene, Trp64Arg in the beta3 -adrenoceptor (ADRB3) gene and C242T in the
      NADPH oxidase p22phox (CYBA) gene on estimated glomerular filtration rate (eGFR)
      in a Chinese population. Initially recruited from different outpatient services
      of HeBei General Hospital in northern China, 668 individuals were finally
      included in the study, with complete demographic information. Laboratory tests
      were performed and estimated glomerular filtration rate (eGFR) was derived from
      the Modification of Diet in Renal Disease (MDRD) equation for the Chinese
      population. Plasma noradrenaline levels and genotype were determined by HPLC and
      the TaqMan method, respectively. Only across the Arg16Gly polymorphism did eGFR
      show significant difference: it was lower in individuals with the Gly16Gly
      variation, who also had the highest plasma noradrenaline levels. This
      polymorphism remained a significant determinant of eGFR after multivariate
      analysis. Of importance, the multifactor dimensionality reduction method further
      detected a significant synergism between the Arg16Gly and C242T polymorphisms in
      reducing eGFR. These observations clarify the effects of the studied
      polymorphisms on eGFR and exemplify gene-gene interactions influencing renal
      function. 

PMID- 24890188
TI  - Brazilian pregnant and lactating women do not change their food intake to meet
      nutritional goals.
AB  - BACKGROUND: Nutritional requirements are increased during pregnancy and
      lactation. The aim of this study was to compare the food intake and prevalence of
      inadequate nutrient intake among pregnant, lactating and reproductive-age women.
      METHODS: Two-day dietary records of 322 pregnant and 751 lactating women were
      compared to those of 6837 non-pregnant and non-lactating women aged 19 to 40
      years from a nationwide representative sample. The usual nutrient intake was
      estimated using the National Cancer Institute method, and compared to nutritional
      goals to estimate prevalence of inadequate intake. RESULTS: Pregnant, lactating
      and reproductive-age women did not differ in their average consumption of 18 food
      groups, except for rice, with greatest intake among lactating women. The
      prevalence of nutrient inadequacy in pregnant women was higher than in
      reproductive-age women for folate (78% versus 40%) and vitamin B6 (59% versus
      33%). In lactating women, prevalence was higher than in reproductive-age women
      for vitamin A (95% versus 72%), vitamin C (56% versus 37%), vitamin B6 (75% vs.
      33%), folate (72% versus 40%) and zinc (64% versus 20%). The percentage of sodium
      intake above the upper limit was greater than 70% in the three groups.
      CONCLUSIONS: Inadequate intake is frequent in women and increases during
      pregnancy and lactation, because women do not change their food intake.
      Guidelines should stimulate healthy food intake for women across the lifespan.

PMID- 24890189
TI  - Increasing fruit, vegetable and water consumption in summer day camps--3-year
      findings of the healthy lunchbox challenge.
AB  - The objective of this study was to describe the 3-year outcomes (2011-2013) from
      the healthy lunchbox challenge (HLC) delivered in the US-based summer day camps
      (SDC) (8-10 hours day(-1), 10-11 weeks summer(-1), SDC) to increase children and
      staff bringing fruit, vegetables and water (FVW) each day. A single group pre-
      with multiple post-test design was used in four large-scale SDCs serving more
      than 550 children day(-1) (6-12 years). The percentage of foods/beverages brought
      by children/staff, staff promotion of healthy eating and children's consumption
      of FVW was assessed via direct observation over 98 days across three summers. For
      children (3308 observations), fruit and vegetables (>11-16%) increased; no
      changes were observed for FVW for staff (398 observations). Reductions in
      unhealthy foods/beverages (e.g. soda/pop and chips) were observed for both
      children and staff (minus -10% to 38%). Staff role modeling unhealthy
      eating/drinking initially decreased but increased by 2013. The majority of
      children who brought fruit/vegetables consumed them. The HLC can influence the
      foods/beverages brought to SDCs. Enhancements are required to further increase
      FVW brought and consumed. 

PMID- 24890190
TI  - Mass media coverage of HPV vaccination in Romania: a content analysis.
AB  - Romania has the highest cervical cancer burden in Europe. Despite the
      implementation of two human papillomavirus (HPV) vaccination programmes, the
      uptake remained extremely low and the programmes were discontinued. Given that
      media are a common source of information for the public and may influence
      vaccination decisions, this article sought to explore the content and quality of
      HPV vaccine media coverage in Romania. We conducted a content analysis of 271
      media reports (from newspapers, magazines, videos and informational websites)
      published online between November 2007 and January 2012. Overall, results
      indicated that 31.4% of the materials were neutral, 28% were negative or
      extremely negative, 17% were mixed, while 23.6% were positive towards the
      vaccine. The most dominant vaccine-related concerns were side effects and
      insufficient testing. Elementary information about the vaccine and HPV was
      constantly left out and sometimes inaccuracies were found. Negatively disposed
      reports were more likely to contain incorrect data about vaccine efficacy and
      less likely to provide comprehensive information about the vaccine and HPV
      related diseases. Some dimensions of media coverage varied across time and media
      outlets. The present findings suggest that educational interventions are greatly
      needed as a response to suboptimal and incomplete media coverage of HPV
      vaccination. 

PMID- 24890198
TI  - A bioinspired catalytic oxygenase cascade to generate complex oxindoles.
AB  - Catalytic, selective, and controlled oxidative functionalization of C-H bonds
      using molecular oxygen as an oxidant remains highly desirable and equally
      challenging in the development of synthetic methodologies. Presented herein is a
      one-pot oxygenase cascade reaction wherein a copper(I)-catalyzed oxygenase
      reaction transforms the allylic methyl group in 3-methylidene oxindoles into an
      aldehyde, which then undergoes an aldol-oxa-Michael addition sequence with beta
      ketoesters to yield dihydrofuran-bearing oxindoles.

PMID- 24890197
TI  - High therapeutic efficiency of magnetic hyperthermia in xenograft models achieved
      with moderate temperature dosages in the tumor area.
AB  - PURPOSE: Tumor cells can be effectively inactivated by heating mediated by
      magnetic nanoparticles. However, optimized nanomaterials to supply thermal stress
      inside the tumor remain to be identified. The present study investigates the
      therapeutic effects of magnetic hyperthermia induced by superparamagnetic iron
      oxide nanoparticles on breast (MDA-MB-231) and pancreatic cancer (BxPC-3)
      xenografts in mice in vivo. METHODS: Superparamagnetic iron oxide nanoparticles,
      synthesized either via an aqueous (MF66; average core size 12 nm) or an organic
      route (OD15; average core size 15 nm) are analyzed in terms of their specific
      absorption rate (SAR), cell uptake and their effectivity in in vivo hyperthermia
      treatment. RESULTS: Exceptionally high SAR values ranging from 658 +/- 53 W*gFe (
      1) for OD15 up to 900 +/- 22 W*gFe (-1) for MF66 were determined in an
      alternating magnetic field (AMF, H = 15.4 kA*m(-1) (19 mT), f = 435 kHz).
      Conversion of SAR values into system-independent intrinsic loss power (ILP, 6.4
      +/- 0.5 nH*m(2)*kg(-1) (OD15) and 8.7 +/- 0.2 nH*m(2)*kg(-1) (MF66)) confirmed
      the markedly high heating potential compared to recently published data. Magnetic
      hyperthermia after intratumoral nanoparticle injection results in dramatically
      reduced tumor volume in both cancer models, although the applied temperature
      dosages measured as CEM43T90 (cumulative equivalent minutes at 43 degrees C) are
      only between 1 and 24 min. Histological analysis of magnetic hyperthermia treated
      tumor tissue exhibit alterations in cell viability (apoptosis and necrosis) and
      show a decreased cell proliferation. CONCLUSIONS: Concluding, the studied
      magnetic nanoparticles lead to extensive cell death in human tumor xenografts and
      are considered suitable platforms for future hyperthermic studies.

PMID- 24890199
TI  - Distance, flow and PCR inhibition: eDNA dynamics in two headwater streams.
AB  - Environmental DNA (eDNA) detection has emerged as a powerful tool for monitoring
      aquatic organisms, but much remains unknown about the dynamics of aquatic eDNA
      over a range of environmental conditions. DNA concentrations in streams and
      rivers will depend not only on the equilibrium between DNA entering the water and
      DNA leaving the system through degradation, but also on downstream transport. To
      improve understanding of the dynamics of eDNA concentration in lotic systems, we
      introduced caged trout into two fishless headwater streams and took eDNA samples
      at evenly spaced downstream intervals. This was repeated 18 times from mid-summer
      through autumn, over flows ranging from approximately 1-96 L/s. We used
      quantitative PCR to relate DNA copy number to distance from source. We found that
      regardless of flow, there were detectable levels of DNA at 239.5 m. The main
      effect of flow on eDNA counts was in opposite directions in the two streams. At
      the lowest flows, eDNA counts were highest close to the source and quickly
      trailed off over distance. At the highest flows, DNA counts were relatively low
      both near and far from the source. Biomass was positively related to eDNA copy
      number in both streams. A combination of cell settling, turbulence and dilution
      effects is probably responsible for our observations. Additionally, during high
      leaf deposition periods, the presence of inhibitors resulted in no amplification
      for high copy number samples in the absence of an inhibition-releasing strategy,
      demonstrating the necessity to carefully consider inhibition in eDNA analysis.

PMID- 24890196
TI  - How the brainstem controls orofacial behaviors comprised of rhythmic actions.
AB  - Mammals perform a multitude of well-coordinated orofacial behaviors such as
      breathing, sniffing, chewing, licking, swallowing, vocalizing, and in rodents,
      whisking. The coordination of these actions must occur without fault to prevent
      fatal blockages of the airway. Deciphering the neuronal circuitry that controls
      even a single action requires understanding the integration of sensory feedback
      and executive commands. A far greater challenge is to understand the coordination
      of multiple actions. Here, we focus on brainstem circuits that drive rhythmic
      orofacial actions. We discuss three neural computational mechanisms that may
      enable circuits for different actions to operate without interfering with each
      other. We conclude with proposed experimental programs for delineating the neural
      control principles that have evolved to coordinate orofacial behaviors. 

PMID- 24890201
TI  - The effects of chalazion excision on corneal surface aberrations.
AB  - PURPOSE: This study is the first to consider the effects of chalazion on corneal
      surface aberrations taking into account of corneal zones, and to establish the
      size standard for the excision of chalazion. METHODS: Twenty three eyes from 23
      patients with central upper eyelid chalazion larger than 3mm were recruited in
      this prospective study. The participants were classified into two groups,
      depending on size of the lesion: Group 1 with lesion size 3-5mm and Group 2 with
      lesion size >5mm Chalazion was excised by standard transconjunctival vertical
      incision. Corneal surface aberrations were measured using a GalileiTM analyzer
      and an auto-refractometer before and 2 months after the excision. RESULTS:
      Corneal astigmatism in all patients decreased significantly in both auto
      refractometer (P=0.012) and GalileiTM (P=0.020) measurements after chalazion
      excision. RMS of total HOAs decreased significantly in 6mm (P=0.043) and 3mm zone
      (P=0.051). The RMS of Zernike orders in the vertical and horizontal trefoil
      decreased significantly in 6mm (P=0.035) and 3mm (P=0.041) zone. Group 2 showed a
      significant decrease in corneal astigmatism in both auto refractometer (P=0.040)
      and GalileiTM (P=0.017) parameters after chalazion excision. Group 1 showed an
      insignificant decrease in corneal astigmatism. Unlike Group 1, the RMS of total
      HOAs and vertical and horizontal trefoil in 6mm zone decreased significantly in
      Group 2 (P<0.05). CONCLUSIONS: The existence of an upper lid chalazion increases
      astigmatism and HOAs, especially at the peripheral cornea. Significantly induced
      astigmatism and HOAs are caused by chalazion >5mm in size. Thus, we recommend the
      surgical excision of chalazion >5mm in size to reduce corneal surface
      aberrations.

PMID- 24890200
TI  - Familial adult onset hyperinsulinism due to an activating glucokinase mutation:
      implications for pharmacological glucokinase activation.
AB  - CONTEXT: Glucokinase (GCK) phosphorylates and thereby "traps" glucose in cells,
      thus serving as a gatekeeper for cellular glucose metabolism, particularly in
      hepatocytes and pancreatic beta cells. In humans, activating GCK mutations cause
      familial hyperinsulinaemic hypoglycaemia (GCK-HH), leading to keen interest in
      the potential of small-molecule glucokinase activators (GKAs) as treatments for
      diabetes mellitus. Many such agents have been developed; however, observation of
      side effects including hypertriglyceridaemia and hepatic steatosis has delayed
      their clinical development. OBJECTIVE: To describe the clinical presentation and
      metabolic profiles of affected family members in a kindred with familial
      hyperinsulinism of adult presentation due to a known activating mutation in GCK.
      DESIGN: Clinical, biochemical and metabolic assessment, and GCK sequencing in
      affected family members. RESULTS: In the 60-year-old female proband,
      hyperinsulinaemic hypoglycaemia (blood glucose 2.1 mmol/mol, insulin 18 pm) was
      confirmed following 34 h of fasting; however, abdominal computed tomography (CT),
      pancreatic MRI, endoscopic ultrasound, octreotide scintigraphy and selective
      arterial calcium stimulation failed to localize an insulinoma. A prolonged OGTT
      revealed fasting hypoglycaemia that was exacerbated after glucose challenge,
      consistent with dysregulated glucose-stimulated insulin release. A heterozygous
      activating mutation, p.Val389Leu, in the glucokinase gene (GCK) was found in the
      proband and four other family members. Of these, two had been investigated
      elsewhere for recurrent hypoglycaemia in adulthood, while the other two adult
      relatives were asymptomatic despite profound hypoglycaemia. All three of the
      available family members with the p.Val389Leu mutation had normal serum lipid
      profiles, normal rates of fasting hepatic de novo lipogenesis and had hepatic
      triglyceride levels commensurate with their degree of adiposity. CONCLUSION:
      Activating GCK mutations may present in late adulthood with hyperinsulinaemic
      hypoglycaemia and should be considered even in older patients being investigated
      for insulinoma. Normal circulating lipids, rates of hepatic de novo lipogenesis
      and appropriate hepatic triglyceride content for degree of adiposity in the
      patients we describe suggest that even lifelong GCK activation in isolation is
      insufficient to produce fatty liver and metabolic dyslipidaemia.

PMID- 24890202
TI  - Relapsing-remitting severe generalized muscular weakness after botulinum toxin
      treatment for hyperhidrosis.

PMID- 24890203
TI  - Measuring endogenous ICRAC and ORAI currents with the patch-clamp technique.
AB  - Although ICRAC and other store-operated currents are often analyzed by Ca(2+)
      imaging, whole-cell patch clamp, described here, is the preferred technique to
      analyze ICRAC whenever possible. The whole-cell patch-clamp protocol can even be
      used to record endogenous ICRAC in primary cells. The small endogenous current
      size of ICRAC requires some precautions: First, it is important to inhibit
      potential interferences from other channels in the cell by carefully choosing the
      combination of pipette and bath solutions. Second, the noise should be <150 fA
      root mean square (RMS) when the pipette holder (with its wire) with or without a
      patch pipette is adjusted over (but not in!) the solution using a high
      amplification gain (50 mV/pA or higher) of the patch-clamp amplifier. In
      addition, this protocol draws attention to measures that should be considered
      when recording ICRAC currents from an overexpression system. This protocol also
      suggests sets of solutions that can be used for distinguishing ICRAC from
      potentially interfering currents. In addition to the solutions, the identity of
      ICRAC can be confirmed by the characteristic inward rectification, its high
      Ca(2+) selectivity, and the reversal potential of more than +50 mV. A few (mostly
      nonspecific) CRAC channel blockers are known, which can also be applied for
      characterization purposes. 

PMID- 24890204
TI  - The minimal requirements to use calcium imaging to analyze ICRAC.
AB  - Endogenous calcium release-activated channel (CRAC) currents are usually quite
      small and not always easy to measure using the patch-clamp technique. While we
      have, for instance, successfully recorded very small CRAC currents in primary
      human effector T cells, we have not yet managed to record CRAC in naive primary
      human T cells. Many groups, including ours, therefore use Ca(2+) imaging
      technologies to analyze CRAC-dependent Ca(2+) influx. However, Ca(2+) signals are
      quite complex and depend on many different transporter activities; thus, it is
      not trivial to make quantitative statements about one single transporter, in this
      case CRAC channels. Therefore, a detailed patch-clamp analysis of ICRAC is always
      preferred. Since many laboratories use Ca(2+) imaging for ICRAC analysis, we
      detail here the minimal requirements for reliable measurements. Ca(2+) signals
      not only depend on the net Ca(2+) influx through CRAC channels but also depend on
      other Ca(2+) influx mechanisms, K(+) channels or Cl(-) channels (which determine
      the membrane potential), Ca(2+) export mechanisms like plasma membrane Ca(2+)
      ATPase (PMCA), sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) or Na(+)-Ca(2+)
      exchangers, and (local) Ca(2+) buffering often by mitochondria. In this protocol,
      we summarize a set of experiments that allow (quantitative) statements about CRAC
      channel activity using Ca(2+) imaging experiments, including the ability to rule
      out Ca(2+) signals from other sources. 

PMID- 24890206
TI  - Manual immunohistochemistry staining of mouse tissues using the avidin-biotin
      complex (ABC) technique.
AB  - There are many variations on the immunohistochemistry (IHC) procedure, but all
      are based on attachment of a primary antibody to a unique epitope on or within
      the cell. This step is followed by incubation of the cell/primary antibody
      complex with another, secondary antibody that recognizes the species in which the
      primary antibody was produced. The secondary antibody has an indicator molecule
      attached to it. The indicator produces a colored reaction product at the site of
      original epitope, allowing visualization. This basic two-antibody "sandwich"
      procedure has many modifications that include other layers of antibodies and
      numerous indicators, but all variations depend upon the unique ability of
      antibodies to recognize specific epitopes or antigenic determinants. The
      procedure described here is called the ABC (avidin-biotin complex) technique. The
      method utilizes the high avidity of biotin for avidin, which allows formation of
      a strong bond. The reagents described in this technique produce a gold/brown
      reaction product that identifies the epitope of interest. 

PMID- 24890205
TI  - Manual hematoxylin and eosin staining of mouse tissue sections.
AB  - The hematoxylin and eosin (H&E) stain is the standard used for microscopic
      examination of tissues that have been fixed, processed, embedded, and sectioned.
      It can be performed manually or by automation. For economic reasons, the manual
      technique is generally the method of choice for facilities with a low sample
      volume. This protocol describes manual H&E staining of fixed, processed, paraffin
      embedded, and sectioned mouse tissues. In H&E-stained tissues, the nucleic acids
      stain dark blue and the proteins stain red to pink or orange. For accurate
      phenotyping and delineation of tissue detail, the protocol must be adhered to
      rigorously. This includes frequent reagent changes as well as the use of "in
      date" reagents. Appropriate color in a good H&E stain allows for identification
      of many tissue subtleties that are necessary for accurate diagnosis. 

PMID- 24890207
TI  - Purification of pericytes from rodent optic nerve by immunopanning.
AB  - This protocol describes the use of immunopanning to purify rodent pericytes from
      the optic nerve. Immunopanning permits the prospective isolation of pericytes
      from optic nerve tissue by relying on the binding of pericytes to an anti
      PDGFRbeta (platelet-derived growth factor receptor beta) antibody adhered to a
      Petri dish. The cells are viable at the end of this gentle procedure, and they
      can be analyzed acutely for gene expression or cultured alone or in coculture
      with other central nervous system (CNS) cell types, including CNS endothelial
      cells and CNS astrocytes. As written, this procedure is used for isolation of
      optic nerve pericytes from the rat. The same PDGFRbeta antibodies can be used for
      purifying optic nerve pericytes from the mouse, but alternate negative panning
      antibodies must be used to ensure that astrocytes do not contaminate the
      preparation. This procedure can also be modified to purify pericytes from the
      brain. The same PDGFRbeta antibody is used, but additional steps (specific
      dissections or negative panning) are required to ensure that other PDGFRbeta
      positive contaminants, including cells from the rostral migratory stream, are
      depleted from the cell suspension. 

PMID- 24890208
TI  - A high-throughput, multiplex cell death assay using an RNAi screening approach.
AB  - This protocol outlines a high-throughput, multiplex cell death assay and its use
      in conjunction with a genome-scale siRNA screen to identify genes that cooperate
      with a drug to induce apoptosis. The assay, ApoLive-Glo (Promega), measures
      viability of drug-treated, reverse-transfected cells via the fluorescent
      CellTiter-Fluor reagent, which includes a substrate that is cleaved by a live
      cell protease. ApoLive-Glo also quantitates cell death by the amount of cleaved
      caspases 3 and 7 using a luminescent Caspase-Glo 3/7 caspase activation assay.
      The advantage of the multiplex assay is that it distinguishes rapid cell death
      from the slower activation of caspase activity, permitting measurement of
      different stages of cell death in the same sample at a single time point. In
      parallel, a high-content imaging protocol involving 4',6-diamidino-2-phenylindole
      stained nuclei is used as a cost-effective way to quantitate viability of vehicle
      treated control cells. Automation and robotic liquid handling are built into the
      protocol to increase speed of workflow and improve reproducibility. A screen
      using these assays will identify gene targets that are essential for viability
      irrespective of drug treatment and gene targets that cause a synergistic
      enhancement of cell death in the presence of drug. Candidate target activity can
      then be validated by conventional flow cytometry-based assays. 

PMID- 24890209
TI  - 3'-End labeling of RNA with yeast Poly(A) polymerase and 3'-deoxyadenosine 5'
      [alpha-32P]triphosphate.
AB  - This protocol is used to label RNA molecules (in vitro-synthesized or in vivo
      purified RNA molecules) that have free 3'-hydroxyl termini. The reaction is
      performed in 10 min using yeast poly(A) polymerase and 3'-deoxyadenosine 5'
      [alpha-(32)P]triphosphate (cordycepin 5'-[alpha-(32)P]triphosphate), a chain
      terminating nucleotide. At the end of the procedure, the reaction is desalted by
      gel filtration to remove any unincorporated nucleotides. 

PMID- 24890210
TI  - RNase footprinting to map sites of RNA-protein interactions.
AB  - The binding of a protein to an RNA sequence protects that the region of the RNA
      from ribonuclease (RNase) digestion; this protected region is known as the
      protein's "footprint." In this protocol, end-labeled RNAs with and without bound
      protein are digested with RNase, and the products of digestion are analyzed by
      gel electrophoresis on denaturing polyacrylamide gels. If the experiment is
      performed properly, a comparison of the banding patterns from the two samples
      will reveal the binding site of the protein. The binding site-or footprint-will
      be detected as a region without bands in the protein-bound sample. In the sample
      without bound protein, the bands should cover the entirety of the RNA molecule.
      To establish appropriate digestion conditions for the procedure (i.e., <=1
      cleavage event per molecule), it is necessary to titrate the amount of RNase
      under a range of time and temperature conditions. RNase I cleaves after every
      nucleotide of RNA and works well under many assay conditions, but other enzymes
      with different cleavage specificities can also be used. RNase VI is preferable
      when analyzing structured RNA; RNase A is preferable when using pyrimidine-rich
      RNAs; and RNase T1 is useful for G-rich RNAs. Choosing enzymes with preference
      for double-stranded (such as RNase VI) versus single-stranded (such as RNase I)
      RNA may be helpful. Often, a combination of nucleases is advantageous. 

PMID- 24890212
TI  - High-speed two-photon calcium imaging of neuronal population activity using
      acousto-optic deflectors.
AB  - Two-photon calcium imaging of neuronal populations allows optical measurements of
      spiking activity in living animals. However, laser-scanning microscopes with
      galvanometric scan mirrors are too slow to capture population activity on a
      millisecond timescale. This protocol describes a two-photon microscope that is
      based on two-dimensional laser scanning with acousto-optic deflectors (AODs),
      enabling high-speed in vivo recording of neuronal population activity at temporal
      resolutions of several hundred hertz. The detailed construction plan of the AOD
      based microscope is accompanied by equally detailed optimization procedures. We
      also introduce a novel random-access pattern scanning (RAPS) technique for high
      speed in vivo measurements of neuronal population activity. AOD-based RAPS can
      measure calcium transients in neocortical neuronal populations, revealing spike
      trains with near-millisecond precision. The current limitations of the AOD-based
      microscope are discussed, and we provide an outlook of its future applications. 

PMID- 24890211
TI  - Reverse footprinting to map sites of RNA-protein interactions.
AB  - Nuclease protection of a site-specifically labeled RNA by an RNA-binding protein
      is an extremely powerful method for determining the site of an RNA-protein
      interaction. If a protein binds to the region that contains the site-specific
      label, it will protect the label and adjoining sequences from nuclease digestion.
      The protected region, or "footprint," can then be characterized by extensive
      fragmentation and gel electrophoresis. As the name implies, reverse footprinting
      produces a mirror image of a conventional footprint; the footprint is revealed by
      the presence, not the absence, of bands. This method has a distinct advantage
      over conventional footprinting in that only a small fraction of the labeled RNA
      must be bound. 

PMID- 24890214
TI  - Patch-clamp measurement of ICRAC and ORAI channel activity.
AB  - Depletion of internal Ca(2+) stores activates store-operated Ca(2+) channels. The
      most prominent members of this class of channels are Ca(2+) release-activated
      Ca(2+) (CRAC) channels, which are present in a variety of cell types including
      immune cells. CRAC channels are composed of ORAI proteins, which are activated by
      endoplasmic reticulum-bound STIM proteins on Ca(2+) store depletion. The
      underlying Ca(2+) current is called ICRAC, which is required for many cellular
      functions including T-cell activation, mast cell activation, Ca(2+)-dependent
      gene expression, and refilling of internal Ca(2+) stores. To analyze ICRAC or the
      Ca(2+) current through heterologously expressed ORAI channels, whole-cell patch
      clamp is the technique of choice. It allows the direct analysis of ion currents
      through CRAC/ORAI channels. The patch-clamp technique has been used to determine
      selectivity, permeability, rectification, inactivation, and several other
      biophysical and pharmacological properties of the channels, and is the most
      direct and reliable technique to analyze ICRAC. 

PMID- 24890213
TI  - Monitoring membrane potential with second-harmonic generation.
AB  - This protocol describes the nonlinear optical phenomenon known as second-harmonic
      generation (SHG) and discusses its special attributes for imaging membrane
      potential changes in single cells and multicellular preparations.
      Undifferentiated N1E-115 mouse neuroblastoma cells are used as a model cellular
      system for membrane electrophysiology. Styryl and naphthylstyryl dyes, also known
      as hemicyanines, are a class of electrochromic membrane-staining probes that have
      been used to monitor membrane potential by fluorescence; they also produce SHG
      images of cell membranes with SHG intensities that are sensitive to voltage.
      These experiments allow for the precise characterization of the voltage
      sensitivity of SHG and identification of the optimal wavelength for the incident
      laser fundamental light. This protocol presents the steps for the culture,
      staining, patching, and imaging of cells. The details of the imaging system and
      the measurements obtained are discussed, as are the prospects of this technology
      for imaging membrane potential changes in neuronal preparations. 

PMID- 24890215
TI  - Analysis of mouse model pathology: a primer for studying the anatomic pathology
      of genetically engineered mice.
AB  - This primer of pathology is intended to introduce investigators to the structure
      (morphology) of cancer with an emphasis on genetically engineered mouse (GEM)
      models (GEMMs). We emphasize the necessity of using the entire biological context
      for the interpretation of anatomic pathology. Because the primary investigator is
      responsible for almost all of the information and procedures leading up to
      microscopic examination, they should also be responsible for documentation of
      experiments so that the microscopic interpretation can be rendered in context of
      the biology. The steps involved in this process are outlined, discussed, and
      illustrated. Because GEMMs are unique experimental subjects, some of the more
      common pitfalls are discussed. Many of these errors can be avoided with attention
      to detail and continuous quality assurance. 

PMID- 24890216
TI  - Purification and culture of central nervous system pericytes.
AB  - Pericytes are found on the abluminal surface of endothelial tubes. The function
      of these cells is still being elucidated, but they have been shown to be
      important for development and maintenance of the blood-brain barrier, regulation
      of angiogenesis and capillary blood flow, and regulation of the neural response
      to injury and disease. Previously used methods to isolate pericytes have relied
      on negative selection and prolonged culture of microvessel cells and may lead to
      populations of pericytes contaminated by other neural cell types. We have
      developed an immunopanning protocol to specifically purify pericytes from
      capillaries in the rodent optic nerve. This method relies on a combination of
      negative and positive selection criteria and allows prospective, acute isolation
      of pericytes. Use of this method will facilitate studies of pericyte cell biology
      and function and pericyte-endothelial cell interactions. 

PMID- 24890217
TI  - High-throughput approaches to measuring cell death.
AB  - Cell death is integral to developmental and disease processes, and high
      throughput screening (HTS) has been instrumental both for understanding
      biological mechanisms underlying cell death and for discovering novel therapeutic
      agents targeting these pathways. The various cell death modalities and their
      distinctive morphological and biochemical features have led to the development of
      a staggering variety of assays to measure these features, many of which have been
      adapted to HTS format. Although not all cell death assays are readily amenable to
      a high-throughput format, the potential power of HTS assays and increasing
      accessibility to associated technology make it likely that new approaches will
      continue to emerge. In particular, many recent studies in this field have used
      multiplex assays and high-content imaging to measure several features
      concurrently. Here, we discuss a broad array of considerations for designing HTS
      cell death assays, including some common challenges and pitfalls. We aim to
      provide a framework for deciding the most appropriate biological readouts, assay
      strategy and mode, workflow, controls, validation, and bioinformatics. 

PMID- 24890218
TI  - Nitrophenyl-based caged neurotransmitters.
AB  - Nitroaromatic photochemical protecting groups were developed for organic
      synthesis in 1966. Since the early 1990s, this type of chromophore has been used
      by neuroscientists to liberate a wide variety of amino acid neurotransmitters
      such as ACh, glutamate, GABA, and glycine, among others. Since 2001, several
      laboratories have used two-photon excitation of nitroaromatic cages for highly
      localized uncaging of glutamate in acute brain slices. 

PMID- 24890219
TI  - Characterization of a novel mutation in the overlap of tlyA and ppnK involved in
      capreomycin resistance in Mycobacterium.
AB  - Capreomycin (CAP) is an important second-line drug for multidrug-resistant
      tuberculosis. To further define the drug resistance mechanism of CAP, a
      Mycobacterium smegmatis transposon mutant library was constructed using Tn5
      transposon for screening isolates with enhanced CAP resistance. A mutant (named
      C4) with fourfold increased CAP resistance was isolated and characterized. Tn5
      was found to be inserted into MSMEG_0841, an annotated pseudogene. However,
      knockout demonstrated that MSMEG_0841 was not responsible for CAP resistance. We
      further sequenced the whole genome of C4 and found an A to G substitution in the
      overlap region between tlyA and ppnK, which leads a stop codon mutation in
      upstream tlyA and a T2A mutation in downstream ppnK. Mutation in the overlap
      might confer the dysfuction of both genes. tlyA is a known gene involved in CAP
      action. Overexpression of ppnK in both Escherichia coli and M. smegmatis confer
      subtle susceptible to CAP. Taken together, our study found that a novel mutation
      involved in CAP resistance.

PMID- 24890220
TI  - Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T
      lymphocyte depot for localized glioblastoma immunotherapy.
AB  - The outcome for glioblastoma patients remains dismal for its invariably
      recrudesces within 2 cm of the resection cavity. Local immunotherapy has the
      potential to eradicate the residual infiltrative component of these tumors. Here,
      we report the development of a biodegradable hydrogel containing therapeutic T
      lymphocytes for localized delivery to glioblastoma cells for brain tumor
      immunotherapy. Thermoreversible poly(ethylene glycol)-g-chitosan hydrogels
      (PCgels) were optimized for steady T lymphocyte release. Nuclear magnetic
      resonance spectroscopy confirmed the chemical structure of poly(ethylene glycol)
      g-chitosan, and rheological studies revealed that the sol-to-gel transition of
      the PCgel occurred around >=32  degrees C. T lymphocyte invasion through the
      PCgel and subsequent cytotoxicity to glioblastoma were assessed in vitro. The
      PCgel was shown to be cellular compatible with T lymphocytes, and the T
      lymphocytes retain their anti-glioblastoma activity after being encapsulated in
      the PCgel. T lymphocytes in the PCgel were shown to be more effective in killing
      glioblastoma than those in the Matrigel control. This may be attributed to the
      optimal pore size of the PCgel allowing better invasion of T lymphocytes. Our
      study suggests that this unique PCgel depot may offer a viable approach for
      localized immunotherapy for glioblastoma. 

PMID- 24890222
TI  - Influence of amodiaquine on the antimalarial activity of ellagic acid:
      crystallographic and biological studies.
AB  - In the search for new antimalarial drugs, design of hybrid molecules is
      recommended to improve biological activity and to decrease the risk of parasite
      resistance development. Ellagic acid, as an inhibitor of Plasmodium glutathione,
      presents an original mode of action and thus appears as a promising
      antiplasmodial compound. A new complex (AQ-EA) consisting of the well-known
      antimalarial drug, amodiaquine, and ellagic acid was obtained. The studied
      crystal structure of AQ-EA showed that the triclinic centrosymmetrical unit cell
      of the crystal contains two molecules of amodiaquine (AQ) and two symmetrically
      independent molecules of ellagic acid (EA). The packing of the molecules in the
      crystal is dominated by hydrogen bonds between AQ and EA. The antiplasmodial
      activity of the hybrid complex AQ-EA was also determined and compared with the
      values of IC50 for AQ and EA separately. Potentiation assays between both
      molecules were conducted to understand the pharmacological interactions between
      AQ and EA against Plasmodium falciparum in vitro. The hybrid complex AQ-EA (IC50
      of 47 nm) showed improved antiplasmodial activity in comparison with EA alone.

PMID- 24890223
TI  - Fe3O4 nanoparticles prepared by the seeded-growth route for hyperthermia:
      electron magnetic resonance as a key tool to evaluate size distribution in
      magnetic nanoparticles.
AB  - Monodispersed Fe3O4 nanoparticles have been synthesized by a thermal
      decomposition method based on the seeded-growth technique, achieving size tunable
      nanoparticles with high crystallinity and high saturation magnetization. EMR
      spectroscopy becomes a very efficient complementary tool to determine the fine
      details of size distributions of MNPs and even to estimate directly the size in a
      system composed of a given type of magnetic nanoparticles. The size and size
      dispersity affect directly the efficiency of MNPs for hyperthermia and EMR
      provides a direct evaluation of these characteristics almost exactly in the same
      preparation and with the same concentration as used in hyperthermia experiments.
      The correlation observed between the Specific Absorption Rate (SAR) and the
      effective gyromagnetic factor (geff) is extremely remarkable and renders a way to
      assess directly the heating capacity of a MNP system. 

PMID- 24890221
TI  - High expression of L-type amino acid transporter 1 as a prognostic marker in bile
      duct adenocarcinomas.
AB  - Oncocytic L-type amino acid transporter (LAT) 1 may be a prognostic indicator and
      target of new molecular therapeutic agents against malignancies. To investigate
      whether LAT1 expression influence the outcomes of patients with bile duct cancer,
      the expression of LAT1, LAT2, CD98, and Ki-67 was investigated
      immunohistochemically in 134 surgically resected bile duct adenocarcinomas,
      including 84 distal extrahepatic bile duct adenocarcinomas, 21 hilar
      cholangiocarcinomas, 15 intrahepatic cholangiocarcinomas, and 14 ampullary
      adenocarcinomas. LAT1 expression was weakly correlated with CD98 expression and
      Ki-67 labeling index (LI). Kaplan-Meier analysis showed a significant difference
      in prognosis between patients with bile duct adenocarcinomas having LAT1-high and
      -low scores, whereas LAT2 and CD98 expression and Ki-67 LI were not predictive of
      poor prognosis. Prognosis tended to be worse in patients having tumors with LAT1
      high/LAT2-low than LAT1-low/LAT2-high scores (P = 0.0686). Multivariable analyses
      revealed that LAT1 expression, surgical margin, pT stage were independent
      prognostic factors. In conclusion, aberrant overexpression of LAT1 in bile duct
      adenocarcinoma predicts poor prognosis, suggesting that LAT1 may be a potential
      target of anticancer therapy. 

PMID- 24890224
TI  - Comparison of propofol with ketofol, a propofol-ketamine admixture, for induction
      of anaesthesia in healthy dogs.
AB  - OBJECTIVE: To compare anaesthetic induction in healthy dogs using propofol or
      ketofol (a propofol-ketamine mixture). STUDY DESIGN: Prospective, randomized,
      controlled, 'blinded' study. ANIMALS: Seventy healthy dogs (33 males and 37
      females), aged 6-157 months and weighing 4-48 kg. METHODS: Following
      premedication, either propofol (10 mg mL(-1)) or ketofol (9 mg propofol and 9 mg
      ketamine mL(-1)) was titrated intravenously until laryngoscopy and tracheal
      intubation were possible. Pulse rate (PR), respiratory rate (f(R)) and arterial
      blood pressure (ABP) were compared to post-premedication values and time to first
      breath (TTFB) recorded. Sedation quality, tracheal intubation and anaesthetic
      induction were scored by an observer who was unaware of treatment group. Mann
      Whitney or t-tests were performed and significance set at p <= 0.05. RESULTS:
      Induction mixture volume (mean +/- SD) was lower for ketofol (0.2 +/- 0.1 mL kg(
      1)) than propofol (0.4 +/- 0.1 mL kg(-1)) (p < 0.001). PR increased following
      ketofol (by 35 +/- 20 beats minute(-1)) but not consistently following propofol
      (4 +/- 16 beats minute(-1)) (p < 0.001). Ketofol administration was associated
      with a higher mean arterial blood pressure (MAP) (82 +/- 10 mmHg) than propofol
      (77 +/- 11) (p = 0.05). TTFB was similar, but ketofol use resulted in a greater
      decrease in f(R) (median (range): ketofol -32 (-158 to 0) propofol -24 (-187 to
      2) breaths minute(-1)) (p < 0.001). Sedation was similar between groups. Tracheal
      intubation and induction qualities were better with ketofol than propofol (p =
      0.04 and 0.02 respectively). CONCLUSION AND CLINICAL RELEVANCE: Induction of
      anaesthesia with ketofol resulted in higher PR and MAP than when propofol was
      used, but lower f(R). Quality of induction and tracheal intubation were
      consistently good with ketofol, but more variable when using propofol.

PMID- 24890225
TI  - Validation of a new catalysed reporter deposition-fluorescence in situ
      hybridization probe for the accurate quantification of marine Bacteroidetes
      populations.
AB  - Catalysed reporter deposition-fluorescence in situ hybridization (CARD-FISH) is a
      powerful approach to quantify bacterial taxa. In this study, we compare the
      performance of the widely used Bacteroidetes CF319a probe with the new CF968
      probe. In silico analyses and tests with isolates demonstrate that CF319a
      hybridizes with non-Bacteroidetes sequences from the Rhodobacteraceae and
      Alteromonadaceae families. We test the probes' accuracy in 37 globally
      distributed marine samples and over two consecutive years at the Blanes Bay
      Microbial Observatory (NW Mediterranean). We also compared the CARD-FISH data
      with the Bacteroidetes 16S rRNA gene sequences retrieved from 27 marine
      metagenomes from the TARA Oceans expedition. We find no significant differences
      in abundances between both approaches, although CF319a targeted some unspecific
      sequences and both probes displayed different abundances of specific
      Bacteroidetes phylotypes. Our results demonstrate that quantitative estimations
      by using both probes are significantly different in certain oceanographic regions
      (Mediterranean Sea, Red Sea and Arabian Sea) and that CF968 shows seasonality
      within marine Bacteroidetes, notably large differences between summer and winter
      that is overlooked by CF319a. We propose CF968 as an alternative to CF319a for
      targeting the whole Bacteroidetes phylum since it has better coverage, greater
      specificity and overall better quantifies marine Bacteroidetes.

PMID- 24890227
TI  - Elevation of fecal eosinophil-derived neurotoxin in infants with food protein
      induced enterocolitis syndrome.

PMID- 24890226
TI  - Perceptions of and barriers to vaccinating daughters against human papillomavirus
      (HPV) among mothers in Hong Kong.
AB  - BACKGROUND: Significant others are noted to be remarkable influences in modelling
      children's and young people's health perceptions and their adoption of health
      behaviour. The vaccinations which a child receives are shown to be significantly
      influenced by his or her parents. However, there is a paucity of Chinese-based
      studies. When discussing the Human Papillomavirus (HPV) vaccine, very few studies
      examine the perceptions of Chinese parents regarding the vaccine as a preventive
      health measure, and even fewer examine how these perceptions of the vaccine and
      sexual values influence their motivations in encouraging their children to be
      vaccinated. In view of the literature gap, this article investigates the
      perceptions of Hong Kong mothers in regard to vaccinating their daughters against
      HPV in Hong Kong. METHODS: A qualitative research approach with individual semi
      structured interviews was conducted with 35 mothers aged 30 to 60 years old with
      daughter(s) between 9 and 17 years old. RESULTS: Six connected themes emerged.
      The participants commonly perceived the HPV vaccination as being unnecessary for
      their daughters in view of their young age. They worried that it would encourage
      their daughters to engage in premarital sex, and perceived the vaccination to be
      potentially harmful to health. Also, their low perceived risk of HPV in addition
      to the lack of reassurance from their health care providers failed to convince
      the participants that the vaccination was important for their daughters' health.
      Finally, the participants found the vaccine to be expensive and perceived it to
      have little protection value in comparison to other optional vaccines.
      CONCLUSION: The sampled mothers did not have a positive perception of the HPV
      vaccine. The cultural association between receiving the vaccination and
      premarital sex was prevalent. Bounded by their cultural values, the participants
      also had many misconceptions regarding the vaccine and the transmission of HPV,
      which discouraged them from having their daughters vaccinated. Furthermore, a
      lack of support from health care providers and the government health authorities
      concerning HPV vaccination failed to provide confidence and reassurance to
      mothers, and conveyed a meaning to these mothers that HPV vaccine is relatively
      unimportant.

PMID- 24890228
TI  - Therapeutic use of a receptor mimic probiotic reduces intestinal Shiga toxin
      levels in a piglet model of hemolytic uremic syndrome.
AB  - BACKGROUND: Hemolytic uremic syndrome (HUS) is a systemic and potentially fatal
      complication of gastroenteritis secondary to Shiga toxin-producing
      enterohemorrhagic Escherichia coli (EHEC) infection characterized by
      microangiopathic hemolytic anemia, thrombocytopenia, and acute renal damage.
      Shiga toxin (Stx), the toxin principle in HUS, is produced locally within the gut
      following EHEC colonization and is disseminated via the vasculature. Clinical
      development of HUS currently has no effective treatment and is a leading cause of
      renal failure in children. Novel post-exposure therapies are currently needed for
      HUS; therefore, the purpose of this study was to investigate the efficacy of a
      Stx receptor mimic probiotic in a porcine model of HUS. Edema disease, an
      infection of swine caused by host adapted Shiga toxin-producing Escherichia coli
      (STEC) and mediated by Shiga toxin 2e (Stx2e), shares many pathogenic
      similarities to HUS. In this study, three-week old piglets were inoculated with
      STEC and 24 hours later treated twice daily with a probiotic expressing an
      oligosaccharide receptor mimic for Stx2e to determine if the probiotic could
      reduce intestinal toxin levels. METHODS: Piglets were orally inoculated with
      10(10) CFU of STEC strain S1191 eight days after weaning. Beginning day 1 post
      inoculation, piglets were treated orally twice daily with 5 * 10(11) CFU of
      either the receptor mimic probiotic or a sham probiotic for 10 days. Intestinal
      Stx2e levels were assessed daily via Vero cell assay. The efficacy of the
      probiotic at reducing intestinal Stx2e, vascular lesions, and clinical disease
      was evaluated with repeated measures ANOVA and Fisher's exact test as
      appropriate. RESULTS: The probiotic significantly reduced intestinal Stx2e, as
      reflected by decreased fecal toxin titers on days 3-8 post-inoculation (p <
      0.01). Despite this reduction in intestinal toxin levels, however, the probiotic
      failed to reduce the incidence of vascular necrosis in target organs and had no
      effect on clinical disease. CONCLUSIONS: The data suggest that post-exposure
      treatment with a Stx-binding probiotic is effective in reducing intestinal toxin
      burden. Future studies could target this approach for possible development of
      post-exposure interventions.

PMID- 24890229
TI  - Who will educate our nurses? A strategy to address the nurse faculty shortage in
      New Jersey.
AB  - BACKGROUND: The nurse faculty shortage hampers the capacity of the nursing
      workforce to respond to the demands of the evolving health care system. As a
      strategy to address the shortage in New Jersey, the Robert Wood Johnson
      Foundation implemented the New Jersey Nursing Initiative Faculty Preparation
      Program to prepare nurses for the faculty role. This article highlights program
      implementation successes and challenges, scholar and faculty perceptions of the
      program, and provides recommendations for others interested in preparing nurse
      faculty. METHODS: This evaluation uses data from scholar surveys and focus
      groups, interviews with grantees, and grantee reports. RESULTS: Findings suggest
      that a program that includes generous monetary support, socialization to the
      nurse faculty role, and formal education courses produces graduates who readily
      assume a faculty position and are committed to at least a part-time career in
      nursing education. CONCLUSIONS: This evaluation emphasizes the need to carefully
      design programs that integrate faculty preparation and advanced clinical
      training.

PMID- 24890230
TI  - The structure-dependent self-association of five phenolic acids in aqueous
      solution.
AB  - Weak self-interaction plays an important role in interpreting the biomechanisms
      and modes of drug action. The structure-dependent self-association of five
      phenolic acids with various bioactivities, including danshensu (DSS), caffeic
      acid (CA), rosmarinic acid (RA), lithospermic acid (LA), and salvianolic acid B
      (SA), was investigated by (1)H NMR. These phenolic acids have similar condensed
      structures, with a CA moiety and varying numbers of DSS moieties. The strengths
      of the self-association constants are in the order DSS < CA < RA < LA < SA, which
      corresponds to the increasing molecular size of these phenolic acids and roughly
      corresponds to the increasing number of DSS moieties. The binding site for the
      self-aggregation of these phenolic acids has been identified to be on the CA
      moiety, rather than on the DSS moiety, as a result of CA's stronger aromatic pi
      pi interactions, which cause larger chemical shift variations. The thermodynamic
      parameters for the self-association of these phenolic acids show that the self
      association is spontaneous and enthalpically favorable at room temperature in all
      cases. It was inferred that pi-pi interactions and intermolecular hydrogen
      bonding stabilize the stacking structures of the phenolic acids. Knowledge of
      self-association processes will enable us to quantitatively assess the possible
      effects of self-aggregation on the interaction between drug and protein.

PMID- 24890231
TI  - Building a strong academic workforce: challenges for the profession.

PMID- 24890232
TI  - Stroke survivors experienced discontinuity in their sense of self and role
      performance in the early stages of recovery from stroke, which impacted on their
      participation but with time they adopted a more proactive attitude.

PMID- 24890233
TI  - Early applied stroke carers training programme was not more effective than usual
      care.

PMID- 24890236
TI  - Opposite the editorial page: introducing a new feature in The Milbank Quarterly.

PMID- 24890237
TI  - Limiting what we can eat: a bridge too far?

PMID- 24890235
TI  - Long-term inhaled granulocyte macrophage-colony-stimulating factor in autoimmune
      pulmonary alveolar proteinosis: effectiveness, safety, and lowest effective dose.
AB  - BACKGROUND AND OBJECTIVES: Granulocyte macrophage-colony-stimulating factor (GM
      CSF) causes variable improvement in autoimmune pulmonary alveolar proteinosis
      (aPAP). Upon response to short-term treatment, patients are divided into
      responders and non-responders. The aim of this study was to test the hypothesis
      that long-term inhaled GM-CSF (iGM-CSF) is effective in all patients and that
      attainment of remission permits gradual de-escalation of the dose to the lowest
      effective safe dose. METHODS: Patients were treated with iGM-CSF 250 MUg once a
      day given 4 days on and 4 days off for as long as necessary (the "as far as it
      takes" protocol). Upon remission, defined as absence of symptoms, oxygen
      desaturation <4 % at the walking test, and significant radiographic reduction of
      the infiltrates, or at least two of the above, the iGM-CSF dose was de-escalated.
      In the case of relapse, the patient was repositioned at the previous effective
      dose. Patients were investigated at 6-month intervals. To detect hematopoietic
      effects, blood cell counts, CD34+ cells, granulocyte macrophage progenitor colony
      forming-units, and burst-forming-unit erythroid were measured. RESULTS: Six (five
      female) patients 43.8 +/- 15.7 years of age were treated for 14-65 months and all
      responded to treatment. Remission was achieved after 25.6 +/- 10 months. Three
      patients maintained remission at their lowest effective dose. Two patients
      relapsed at de-escalating doses. One patient remains on full-dose treatment. iGM
      CSF had no impact on any of the hematological parameters tested. CONCLUSIONS: In
      aPAP, long-term adherence to the dose schedule permitted remission in all
      patients. Long-term treatment with iGM-CSF also permitted the definition of lower
      effective doses, minimizing disease burden and treatment costs safely, since no
      stimulating activity on hematopoiesis was observed, a fact that is of paramount
      importance for those aPAP patients needing lifelong treatment.

PMID- 24890238
TI  - The perils of health care nostalgia.

PMID- 24890239
TI  - Medicare physician payment reform in 2014 is looking unlikely.

PMID- 24890240
TI  - On working for Henry Waxman.

PMID- 24890241
TI  - The long struggle to protect workers' lungs against silicosis.

PMID- 24890242
TI  - Conflicts of interest in medical practice and their costs to the nation's health
      and health care system.

PMID- 24890243
TI  - Justice, population health, and tobacco control.

PMID- 24890244
TI  - When religion meets workers' rights: Hobby Lobby and Conestoga Wood Specialties.

PMID- 24890245
TI  - Waiting for the opportune moment: the tobacco industry and marijuana
      legalization.
AB  - CONTEXT: In 2012, Washington State and Colorado legalized the recreational use of
      marijuana, and Uruguay, beginning in 2014, will become the first country to
      legalize the sale and distribution of marijuana. The challenge facing
      policymakers and public health advocates is reducing the harms of an ineffective,
      costly, and discriminatory "war on drugs" while preventing another public health
      catastrophe similar to tobacco use, which kills 6 million people worldwide each
      year. METHODS: Between May and December 2013, using the standard snowball
      research technique, we searched the Legacy Tobacco Documents Library of
      previously secret tobacco industry documents (http://legacy.library.ucsf.edu).
      FINDINGS: Since at least the 1970s, tobacco companies have been interested in
      marijuana and marijuana legalization as both a potential and a rival product. As
      public opinion shifted and governments began relaxing laws pertaining to
      marijuana criminalization, the tobacco companies modified their corporate
      planning strategies to prepare for future consumer demand. CONCLUSIONS:
      Policymakers and public health advocates must be aware that the tobacco industry
      or comparable multinational organizations (eg, food and beverage industries) are
      prepared to enter the marijuana market with the intention of increasing its
      already widespread use. In order to prevent domination of the market by companies
      seeking to maximize market size and profits, policymakers should learn from their
      successes and failures in regulating tobacco.

PMID- 24890246
TI  - Experimenting with pot: the state of Colorado's legalization of marijuana.

PMID- 24890247
TI  - Changing policy framing as a deliberate strategy for public health advocacy: a
      qualitative policy case study of minimum unit pricing of alcohol.
AB  - CONTEXT: Scotland is the first country in the world to pass legislation
      introducing a minimum unit price (MUP) for alcohol in an attempt to reduce
      consumption and associated harms by increasing the price of the cheapest alcohol.
      We investigated the competing ways in which policy stakeholders presented the
      debate. We then established whether a change in framing helped explain the
      policy's emergence. METHODS: We conducted a detailed policy case study through
      analysis of evidence submitted to the Scottish parliament, and in-depth, one-to
      one interviews (n = 36) with politicians, civil servants, advocates, researchers,
      and industry representatives. FINDINGS: Public- and voluntary-sector stakeholders
      tended to support MUP, while industry representatives were more divided. Two
      markedly different ways of presenting alcohol as a policy problem were evident.
      Critics of MUP (all of whom were related to industry) emphasized social disorder
      issues, particularly among young people, and hence argued for targeted
      approaches. In contrast, advocates for MUP (with the exception of those in
      industry) focused on alcohol as a health issue arising from overconsumption at a
      population level, thus suggesting that population-based interventions were
      necessary. Industry stakeholders favoring MUP adopted a hybrid framing,
      maintaining several aspects of the critical framing. Our interview data showed
      that public health advocates worked hard to redefine the policy issue by
      deliberately presenting a consistent alternative framing. CONCLUSIONS: Framing
      alcohol policy as a broad, multisectoral, public health issue that requires a
      whole-population approach has been crucial to enabling policymakers to seriously
      consider MUP, and public health advocates intentionally presented alcohol policy
      in this way. This reframing helped prioritize public health considerations in the
      policy debate and represents a deliberate strategy for consideration by those
      advocating for policy change around the world and in other public health areas.

PMID- 24890248
TI  - "It's the population, stupid": why changing the policy frame should help Scotland
      tackle its problem with cheap alcohol.

PMID- 24890249
TI  - The role of stigma in access to health care for the poor.
AB  - CONTEXT: The Affordable Care Act provides new Medicaid coverage to an estimated
      12 million low-income adults. Barriers to access or quality could hamper the
      program's success. One of these barriers might be the stigma associated with
      Medicaid or poverty. METHODS: Our mixed-methods study involved 574 low-income
      adults and included data from an in-person survey and follow-up interviews. Our
      analysis of the interviews showed that many participants who were on Medicaid or
      uninsured described a perception or fear of being treated poorly in the health
      care setting. We defined this experience as stigma and merged our qualitative
      interviews coded for stigma with our quantitative survey data to see whether
      stigma was related to other sociodemographic characteristics. We also examined
      whether stigma was associated with access to care, quality of care, and self
      reported health. FINDINGS: We were unable to identify other sociodemographic
      characteristics associated with stigma in this low-income sample. The qualitative
      interviews suggested that stigma was most often the result of a provider-patient
      interaction that felt demeaning, rather than an internalized sense of shame
      related to receiving public insurance or charity care. An experience of stigma
      was associated with unmet health needs, poorer perceptions of quality of care,
      and worse health across several self-reported measures. CONCLUSIONS: Because a
      stigmatizing experience in the health system might interfere with the delivery of
      high-quality care to new Medicaid enrollees, further research and policy
      interventions that target stigma are warranted.

PMID- 24890250
TI  - What are the key ingredients for effective public involvement in health care
      improvement and policy decisions? A randomized trial process evaluation.
AB  - CONTEXT: In the past 50 years, individual patient involvement at the clinical
      consultation level has received considerable attention. More recently, patients
      and the public have increasingly been involved in collective decisions concerning
      the improvement of health care and policymaking. However, rigorous evaluation
      guiding the development and implementation of effective public involvement
      interventions is lacking. This article describes those key ingredients likely to
      affect public members' ability to deliberate productively with professionals and
      influence collective health care choices. METHOD: We conducted a trial process
      evaluation of public involvement in setting priorities for health care
      improvement. In all, 172 participants (including 83 patients and public members
      and 89 professionals) from 6 Health and Social Services Centers in Canada
      participated in the trial. We video-recorded 14 one-day meetings, and 2
      nonparticipant observers took structured notes. Using qualitative analysis, we
      show how public members influenced health care improvement priorities. FINDINGS:
      Legitimacy, credibility, and power explain the variations in the public members'
      influence. Their credibility was supported by their personal experience as
      patients and caregivers, the provision of a structured preparation meeting, and
      access to population-based data from their community. Legitimacy was fostered by
      the recruitment of a balanced group of participants and by the public members'
      opportunities to draw from one another's experience. The combination of small
      group deliberations, wider public consultation, and a moderation style focused on
      effective group process helped level out the power differences between
      professionals and the public. The engagement of key stakeholders in the
      intervention design and implementation helped build policy support for public
      involvement. CONCLUSIONS: A number of interacting active ingredients structure
      and foster the public's legitimacy, credibility, and power. By paying greater
      attention to them, policymakers could develop and implement more effective public
      involvement interventions.

PMID- 24890251
TI  - How successful is Medicare Advantage?
AB  - CONTEXT: Medicare Part C, or Medicare Advantage (MA), now almost 30 years old,
      has generally been viewed as a policy disappointment. Enrollment has vacillated
      but has never come close to the penetration of managed care plans in the
      commercial insurance market or in Medicaid, and because of payment policy
      decisions and selection, the MA program is viewed as having added to cost rather
      than saving funds for the Medicare program. Recent changes in Medicare policy,
      including improved risk adjustment, however, may have changed this picture.
      METHODS: This article summarizes findings from our group's work evaluating MA's
      recent performance and investigating payment options for improving its
      performance even more. We studied the behavior of both beneficiaries and plans,
      as well as the effects of Medicare policy. FINDINGS: Beneficiaries make
      "mistakes" in their choice of MA plan options that can be explained by behavioral
      economics. Few beneficiaries make an active choice after they enroll in Medicare.
      The high prevalence of "zero-premium" plans signals inefficiency in plan design
      and in the market's functioning. That is, Medicare premium policies interfere
      with economically efficient choices. The adverse selection problem, in which
      healthier, lower-cost beneficiaries tend to join MA, appears much diminished. The
      available measures, while limited, suggest that, on average, MA plans offer care
      of equal or higher quality and for less cost than traditional Medicare (TM). In
      counties, greater MA penetration appears to improve TM's performance.
      CONCLUSIONS: Medicare policies regarding lock-in provisions and risk adjustment
      that were adopted in the mid-2000s have mitigated the adverse selection problem
      previously plaguing MA. On average, MA plans appear to offer higher value than
      TM, and positive spillovers from MA into TM imply that reimbursement should not
      necessarily be neutral. Policy changes in Medicare that reform the way that
      beneficiaries are charged for MA plan membership are warranted to move more
      beneficiaries into MA.

PMID- 24890253
TI  - Rapid diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis using
      a molecular-based diagnostic algorithm.
AB  - There is an urgent need for rapid and accurate diagnosis of pyrazinamide
      resistant multidrug-resistant tuberculosis (MDR-TB). No diagnostic algorithm has
      been validated in this population. We hypothesized that pncA sequencing added to
      rpoB mutation analysis can accurately identify patients with pyrazinamide
      resistant MDR-TB. We identified from the Dutch national database (2007-11)
      patients with a positive Mycobacterium tuberculosis culture containing a mutation
      in the rpoB gene. In these cases, we prospectively sequenced the pncA gene.
      Results from the rpoB and pncA mutation analysis (pncA added to rpoB) were
      compared with phenotypic susceptibility testing results to rifampicin, isoniazid
      and pyrazinamide (reference standard) using the Mycobacterial Growth Indicator
      Tube 960 system. We included 83 clinical M. tuberculosis isolates containing rpoB
      mutations in the primary analysis. Rifampicin resistance was seen in 72 isolates
      (87%), isoniazid resistance in 73 isolates (88%) and MDR-TB in 65 isolates (78%).
      Phenotypic reference testing identified pyrazinamide-resistant MDR-TB in 31
      isolates (48%). Sensitivity of pncA sequencing added to rpoB mutation analysis
      for detecting pyrazinamide-resistant MDR-TB was 96.8%, the specificity was 94.2%,
      the positive predictive value was 90.9%, the negative predictive value was 98.0%,
      the positive likelihood was 16.8 and the negative likelihood was 0.03. In
      conclusion, pyrazinamide-resistant MDR-TB can be accurately detected using pncA
      sequencing added to rpoB mutation analysis. We propose to include pncA sequencing
      in every isolate with an rpoB mutation, allowing for stratification of MDR-TB
      treatment according to pyrazinamide susceptibility.

PMID- 24890254
TI  - A systematic review and meta-analysis of gastric cancer treatment in patients
      with positive peritoneal cytology.
AB  - Gastric cancer patients with positive peritoneal cytology as the only marker of
      metastatic disease have poor prognoses. There is no universal consensus on the
      most appropriate treatment regimen for this particular patient group. We reviewed
      and analyzed published data to determine the optimal treatment regimen for
      patients with peritoneal cytology-positive gastric adenocarcinomas. Six
      electronic databases were explored [PubMed, Cochrane (Systematic Reviews and
      Controlled Trials), PROSPERO, DARE, and EMBASE]. The primary outcome was overall
      survival with secondary outcomes including patterns of recurrence and treatment
      related morbidity. Six studies were included for data extraction. There was no
      significant heterogeneity between studies. The use of S1 monotherapy was
      associated with a significant survival benefit (HR 0.48; 95% CI 0.32-0.70; p =
      0.0002). Intraoperative intraperitoneal chemotherapy (IIPC) with adjuvant
      chemotherapy showed a trend toward improvement in overall survival (HR 0.70; 9 %
      CI 0.47-1.04; p = 0.08). A recent randomized controlled trial examining extensive
      intraperitoneal lavage (EIPL) with IIPC showed a significant improvement in
      overall survival (5-year overall survival, 43.8% for EIPL-IPC group compared with
      4.6% for IPC group). However, these promising results need to be validated in
      larger prospective randomized trials.

PMID- 24890255
TI  - Gastric cancer in patients with type I gastric carcinoids.
AB  - BACKGROUND: Atrophic body gastritis (ABG) is associated with both type I gastric
      carcinoids (T1-GCs) and intestinal-type gastric cancer. The occurrence of gastric
      cancer in ABG patients with type I gastric carcinoids has not yet been described.
      AIM: To describe the occurrence at follow-up of gastric cancer in ABG patients
      with type I gastric carcinoid in a retrospective case series in a single tertiary
      referral center. METHODS: Between 1994 and 2012, 17 new cases of T1-GCs were
      diagnosed among a cohort of ABG patients in a single tertiary referral center for
      ABG. The clinical charts of these 17 T1-GC patients were retrospectively
      evaluated for the occurrence of gastric cancer at follow-up (median 4.2 years,
      range 0.5-13). RESULTS: In 4 (23.5 %)/17 T1-GCs patients (3 females, age 40-78
      years), gastric cancer occurred (median follow-up 5.9 years, range 5.1-13). Three
      cases were intestinal-type adenocarcinomas and one a signet-ring cell diffuse
      gastric cancer, localized in three cases in the antrum. In two patients, it was
      detected on random biopsies during follow-up gastroscopy; in the other two,
      gastroscopy was performed because of new symptoms. All patients with gastric
      cancer had associated autoimmune features (pernicious anemia, autoimmune thyroid
      disease and a spared antrum) compared to 77, 46 and 54 % of those without gastric
      cancer, although statistical significance was not reached. CONCLUSIONS: This case
      series shows that in patients with T1-GCs, gastric cancer may frequently occur at
      long-term follow-up. Thus, these patients should be monitored by a long-term
      surveillance program, including an accurate bioptic sampling of the antral
      mucosa.

PMID- 24890256
TI  - Cesarean scar pregnancy is a precursor of morbidly adherent placenta.
AB  - OBJECTIVE: To provide further sonographic, clinical and histological evidence
      that Cesarean scar pregnancy (CSP) is a precursor to and an early form of second-
      and third-trimester morbidly adherent placenta (MAP). METHODS: This is a report
      of 10 cases of CSP identified early, in which the patients decided to continue
      the pregnancy, following counseling that emphasized the possibility of both
      significant pregnancy complications and a need for hysterectomy. Pregnancies were
      followed at 2-4-week intervals with ultrasound scans and customary monitoring.
      The aim was for patients to reach near term or term and then undergo elective
      Cesarean delivery and, if necessary, hysterectomy. Charts, ultrasound images,
      operative reports and histopathological examinations of the placentae were
      reviewed. RESULTS: The ultrasound diagnosis of CSP was made before 10 weeks. By
      the second trimester, all patients exhibited sonographic signs of MAP. Nine of
      the 10 patients delivered liveborn neonates between 32 and 37 weeks. In the tenth
      pregnancy, progressive shortening of the cervix and intractable vaginal bleeding
      prompted termination, with hysterectomy, at 20 weeks. Two other patients in the
      cohort had antepartum complications (bleeding at 33 weeks in one case and
      contractions at 32 weeks in the other). All patients underwent hysterectomy at
      the time of Cesarean delivery, with total blood loss ranging from 300 to 6000 mL.
      Placenta percreta was the histopathological diagnosis in all 10 cases.
      CONCLUSION: The cases in this series validate the hypothesis that CSP is a
      precursor of MAP, both sharing the same histopathology. Our findings provide
      evidence that can be used to counsel patients with CSP, to enable them to make an
      informed choice between first-trimester termination and continuation of the
      pregnancy, with its risk of premature delivery and loss of uterus and fertility.

PMID- 24890257
TI  - The effect of dental insurance on the use of dental care for older adults: a
      partial identification analysis.
AB  - We evaluate the impact of dental insurance on the use of dental services using a
      potential outcomes identification framework designed to handle uncertainty
      created by unknown counterfactuals-that is, the endogenous selection problem-and
      uncertainty about the reliability of self-reported insurance status. Using data
      from the health and retirement study, we estimate that utilization rates of
      adults older than 50 years would increase from 75% to around 80% under universal
      dental coverage.

PMID- 24890258
TI  - Zerumbone suppresses IL-1beta-induced cell migration and invasion by inhibiting
      IL-8 and MMP-3 expression in human triple-negative breast cancer cells.
AB  - Inflammation is a key regulatory process in cancer development. Prolonged
      exposure of breast tumor cells to inflammatory cytokines leads to epithelial
      mesenchymal transition, which is the principal mechanism involved in metastasis
      and tumor invasion. Interleukin (IL)-1beta is a major inflammatory cytokine in a
      variety of tumors. To date, the regulatory mechanism of IL-1beta-induced cell
      migration and invasion has not been fully elucidated. Here, we investigated the
      effect of zerumbone (ZER) on IL-1beta-induced cell migration and invasion in
      breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA
      were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8
      and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western
      blot analysis, respectively. Cell invasion and migration was detected by Boyden
      chamber assay. The levels of IL-8 and MMP-3 expression were significantly
      increased by IL-1beta treatment in Hs578T and MDA-MB231 cells. On the other hand,
      IL-1beta-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL
      1beta-induced cell migration and invasion were decreased by ZER in Hs578T and MDA
      MB231 cells. ZER suppresses IL-1beta-induced cell migration and invasion by
      inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a
      promising therapeutic drug for treatment of triple-negative breast cancer
      patients.

PMID- 24890259
TI  - VEGF pathway inhibitors-induced hypertension: next step in therapy.

PMID- 24890260
TI  - Commentary: PDA--public display of affection or pathological demand avoidance?-
      reflections on O'Nions et al. (2014).
AB  - A group of children presents with a rather peculiar type of oppositional
      behaviours, sometimes now subsumed under the label of 'pathological demand
      avoidance' syndrome, also increasingly referred to as PDA. Boys and girls with
      'this kind of PDA' will do anything to avoid meeting demands of adults and
      children alike. The behaviours 'used' in maintaining avoidance range from openly
      oppositional or manipulative to 'extreme shyness', passivity and muteness. These
      behaviours in terms of expression of affection are rather the opposite of those
      associated with the commonly used meaning of PDA. However, the avoidant behaviour
      is quite often 'publicly displayed' and with no feeling for the inappropriateness
      of the, sometimes even, exhibitionist style of extreme demand avoidance (EDA).
      The 'disorder' was first heard of in 1980, when Elisabeth Newson presented the
      first 12 cases of what she believed to be a 'new' and separate syndrome and that
      she referred to as PDA. Even though PDA has attracted quite a bit of clinical
      attention in the United Kingdom and other parts of Europe (including
      Scandinavia), virtually no research has been published in the field so far
      (Newson, Le Marechal, & David, ). Experienced clinicians throughout child
      psychiatry, child neurology and paediatrics testify to its existence and the very
      major problems encountered when it comes to intervention and treatment. It is
      therefore a major step forward that O'Nions and co-workers (this issue) have
      developed a new 'trait measure' for PDA ('the EDA-Q'), a measure that appears to
      hold considerable promise for research, and eventually for clinical practice. 

PMID- 24890262
TI  - Differences between immigrants at various durations of residence and host
      population in all-cause mortality, Canada 1991-2006.
AB  - We used data from the 1991-2006 Canadian Census Mortality and Cancer Follow-up
      Study to compare all-cause mortality for immigrants with that of the Canadian
      born population. The study addressed two related questions. First, do immigrants
      have a mortality advantage over the Canadian-born? Second, if immigrants have a
      mortality advantage, does it persist as their duration of residence increases?
      The analysis fitted sex-stratified hazard regression models for the overall
      sample and for selected countries of birth (UK, China, India, Philippines, and
      the Caribbean). Predictors were assessed at baseline. Mortality was lower among
      immigrants than the Canadian-born even after adjusting for a selected group of
      socio-demographic and socio-economic factors. The mortality differences persisted
      even after long residence in Canada, but appeared to be dependent on the age of
      the individual and the country of origin. Interpreted in light of known
      explanations of immigrant mortality advantage, the results mostly reflect
      selection effects. 

PMID- 24890261
TI  - Integrating the automatic and the controlled: strategies in semantic priming in
      an attractor network with latching dynamics.
AB  - Semantic priming has long been recognized to reflect, along with automatic
      semantic mechanisms, the contribution of controlled strategies. However, previous
      theories of controlled priming were mostly qualitative, lacking common grounds
      with modern mathematical models of automatic priming based on neural networks.
      Recently, we introduced a novel attractor network model of automatic semantic
      priming with latching dynamics. Here, we extend this work to show how the same
      model can also account for important findings regarding controlled processes.
      Assuming the rate of semantic transitions in the network can be adapted using
      simple reinforcement learning, we show how basic findings attributed to
      controlled processes in priming can be achieved, including their dependency on
      stimulus onset asynchrony and relatedness proportion and their unique effect on
      associative, category-exemplar, mediated and backward prime-target relations. We
      discuss how our mechanism relates to the classic expectancy theory and how it can
      be further extended in future developments of the model. 

PMID- 24890263
TI  - Impact of a quality improvement intervention on nurses' management of same-day
      primary care flow.
AB  - AIM: To evaluate the impact of an interdisciplinary intervention designed to
      improve the capacity of nurses to manage walk-in patient demand for primary
      health care. BACKGROUND: Implementation of a programme to expand nursing practice
      is a complex process that requires the application of context-appropriate
      measures and adaptation when results do not meet expectations. METHODS: A
      longitudinal, uncontrolled intervention study with a 3-year follow-up, from 2009
      to 2012, was carried out in Catalonia (northeast Spain). The intervention
      included three training periods focused on clinical and instrumentation topics.
      The capacity of nurses to manage walk-in patient demand was assessed by
      determining the number of cases resolved and of return visits for the same
      complaint within 72 hours. RESULTS: In total, 2751 patient care demands were
      evaluated. Resolved cases increased (chi(2)  = 54.624, df = 1, P < 0.001) and the
      number of return visits decreased (chi(2)  = 54.585, df = 1, P < 0.001)
      significantly from baseline to the end of the study period. CONCLUSIONS: Nurses'
      capacity to manage walk-in patient demand improved after an interdisciplinary
      intervention using a mutually agreed upon, locally adapted approach. IMPLICATIONS
      FOR NURSING MANAGEMENT: To improve outcomes, nurses in management positions
      should systematically consider the need for skills training, specific academic
      courses, leadership development and, as appropriate, legislative initiatives.

PMID- 24890264
TI  - Salivary antimicrobial proteins associate with age-related changes in
      streptococcal composition in dental plaque.
AB  - Secretion of antimicrobial proteins (AMPs) and salivary antibodies can modify
      biofilm formation at host body surfaces. In adolescents, associations have been
      reported between dental caries and salivary AMPs. AMPs demonstrate direct
      antimicrobial effects at high concentrations, and at lower more physiological
      concentrations they mediate changes in host cell defenses, which may alter the
      local environment and indirectly shape local biofilm formation. The expression of
      salivary AMPs in preschool children, at an age when the oral bacteria are known
      to change, has not been investigated. We sought to investigate salivary AMP
      expression in the context of previously well-documented changes in the oral
      cavities of this age group including salivary immunoglobulin A (IgA), oral
      bacteria and dental caries. Dental plaque and saliva were collected from 57
      children aged 12-24 months at baseline, of whom 23 children were followed-up at 3
      years of age. At each time, saliva was assessed for LL37, human neutrophil
      peptides 1-3, calprotectin, lactoferrin, salivary IgA, total plaque bacteria and
      Streptococcus mutans. Over time, concentrations of AMPs, S. mutans and bacteria
      specific salivary IgA increased. Caries experience was also recorded when
      children were 3 years old. Concentrations of AMPs were highest in the saliva of 3
      year-old children with the greatest burden of S. mutans. These data suggest that
      salivary AMPs are variable over time and between individuals, and are linked with
      bacterial colonization. At follow up, the majority of children remained caries
      free. Larger longitudinal studies are required to confirm whether salivary AMP
      levels are predictive of caries and whether their modulation offers therapeutic
      benefit.

PMID- 24890265
TI  - Light exposure leads to reorganization of microglomeruli in the mushroom bodies
      and influences juvenile hormone levels in the honeybee.
AB  - Honeybees show a remarkable behavioral plasticity at the transition from nursing
      inside the hive to foraging for nectar and/or pollen outside. This plasticity is
      important for age-related division of labor in honeybee colonies. The behavioral
      transition is associated with significant volume and synaptic changes in the
      mushroom bodies (MBs), brain centers for sensory integration, learning, and
      memory. We tested whether precocious sensory exposure to light leads to changes
      in the density of synaptic complexes [microglomeruli (MG)] in the MBs. The
      results show that exposure to light pulses over 3 days induces a significant
      decrease in the MG density in visual subregions (collar) of the MB. Earlier
      studies had shown that foragers have increased levels of juvenile hormone (JH) co
      occurring with a decrease of vitellogenin (Vg). Previous work further established
      that RNAi-mediated knockdown of vg and ultraspiracle (usp) induced an
      upregulation of JH levels, which can lead to precocious foraging. By disturbing
      both Vg and JH pathways using gene knockdown of vg and usp, we tested whether the
      changes in the hormonal system directly affect MG densities. Our study shows that
      MG numbers remained unchanged when Vg and JH pathways were perturbed, suggesting
      no direct hormonal influences on MG densities. However, mass spectrometry
      detection of JH revealed that precocious light exposure triggered an increase in
      JH levels in the hemolymph (HL) of young bees. This suggests a dual effect
      following light exposure via direct effects on MG reorganization in the MB calyx
      and a possible positive feedback on HL JH levels.

PMID- 24890266
TI  - Climate sensitivity across marine domains of life: limits to evolutionary
      adaptation shape species interactions.
AB  - Organisms in all domains, Archaea, Bacteria, and Eukarya will respond to climate
      change with differential vulnerabilities resulting in shifts in species
      distribution, coexistence, and interactions. The identification of unifying
      principles of organism functioning across all domains would facilitate a cause
      and effect understanding of such changes and their implications for ecosystem
      shifts. For example, the functional specialization of all organisms in limited
      temperature ranges leads us to ask for unifying functional reasons. Organisms
      also specialize in either anoxic or various oxygen ranges, with animals and
      plants depending on high oxygen levels. Here, we identify thermal ranges, heat
      limits of growth, and critically low (hypoxic) oxygen concentrations as proxies
      of tolerance in a meta-analysis of data available for marine organisms, with
      special reference to domain-specific limits. For an explanation of the patterns
      and differences observed, we define and quantify a proxy for organismic
      complexity across species from all domains. Rising complexity causes heat (and
      hypoxia) tolerances to decrease from Archaea to Bacteria to uni- and then
      multicellular Eukarya. Within and across domains, taxon-specific tolerance limits
      likely reflect ultimate evolutionary limits of its species to acclimatization and
      adaptation. We hypothesize that rising taxon-specific complexities in structure
      and function constrain organisms to narrower environmental ranges. Low complexity
      as in Archaea and some Bacteria provide life options in extreme environments. In
      the warmest oceans, temperature maxima reach and will surpass the permanent
      limits to the existence of multicellular animals, plants and unicellular
      phytoplankter. Smaller, less complex unicellular Eukarya, Bacteria, and Archaea
      will thus benefit and predominate even more in a future, warmer, and hypoxic
      ocean. 

PMID- 24890268
TI  - Amenorrhea secondary to a vismodegib-induced blockade of follicle-stimulating
      hormone-receptor activation.
AB  - OBJECTIVE: To report a novel mechanism suggestive of early ovarian failure
      secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib. DESIGN: Case
      report and literature review. SETTING: Academic and private dermatology and
      fertility practices. PATIENT(S): A 34-year-old nulliparous woman with locally
      advanced basal cell carcinomas who became amenorrheic while receiving oral
      therapy with vismodegib. INTERVENTION(S): Physical examination and endocrine
      evaluation. MAIN OUTCOME MEASURE(S): Elevated follicle-stimulating hormone (FSH)
      and low estrogen in the setting of a normal anti-Mullerian hormone. RESULT(S):
      FSH was elevated; estrogen was low. Preantral follicles were detected and anti
      Mullerian hormone activity was normal. Menses resumed 5 weeks after cessation of
      therapy. CONCLUSION(S): Vismodegib, a first-in-class inhibitor of the hedgehog
      signaling pathway is indicated for advanced basal cell carcinoma and is
      associated with amenorrhea. The mechanism is unknown; it has some features of
      ovarian failure but preserves ovarian potential through blockading of FSH
      receptor-dependent signal transduction. This effect appears to be rapidly
      reversible upon cessation of therapy. Vismodegib and related compounds may have
      potential for a role in intervention for gynecologic and endocrine disorders and
      in therapy for other issues involving FSH-dependent function.

PMID- 24890269
TI  - Blastulation rates decline in a linear fashion from euploid to aneuploid embryos
      with single versus multiple chromosomal errors.
AB  - OBJECTIVE: To test the hypothesis that the blastulation rate is higher in euploid
      embryos than in aneuploid embryos as assessed by cleavage-stage biopsy with array
      comprehensive genomic hybridization (aCGH). DESIGN: Retrospective cohort study.
      SETTING: University-affiliated institution. PATIENT(S): Forty-one patients with
      48 in vitro fertilization (IVF) cycles and 385 embryos that underwent cleavage
      stage preimplantation genetic screening (PGS) with aCGH at the Continuum
      Reproductive Center between January 2010 and September 2013. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Probability of blastocyst and/or fully expanded or
      hatching blastocyst (FEHB) progression depending on number of chromosomal
      abnormalities. RESULT(S): Euploid embryos are twice as likely to progress to
      blastocyst and three times as likely to progress to FEHB than aneuploid embryos:
      76% versus 37% and 56% versus 18%, respectively. For every additional chromosomal
      abnormality, the likelihood of progressing to the blastocyst stage decreases by
      22% and the likelihood of progressing to FEHB decreases by 33%. CONCLUSION(S):
      Euploid embryos are far more likely than aneuploid embryos to progress to the
      blastocyst and FEHB stages. There is a linear decrease in probability of
      blastulation with the increasing number of chromosomal abnormalities.

PMID- 24890270
TI  - Current understanding of somatic stem cells in leiomyoma formation.
AB  - OBJECTIVE: To provide a detailed summary of current scientific knowledge of
      somatic stem cells (SSCs) in murine and human myometrium and their putative
      implication in leiomyoma formation, as well as to establish new therapeutic
      options. DESIGN: Pubmed and Scholar One manuscripts were used to identify the
      most relevant studies on SSCs and their implications in human myometrium and
      leiomyomas. SETTING: University research laboratory-affiliated infertility
      clinic. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME
      MEASURE(S): Not applicable. RESULT(S): Despite numerous publications on SSCs, it
      was not until 2007 that scientific evidence based on the use of 5-bromo-2'
      deoxyuridine (BrdU) and side population (SP) methods in murine and human
      myometrium were first published. Recently, it has been reported that SP cells are
      present in human leiomyomas; however, to date the pathogenesis of this benign
      tumor remains unclear. Besides many genetic/epigenetic alterations, changes to
      steroid hormones and growth factors may also be associated with the impaired
      function, proliferation, and differentiation of a subset of putative SSCs in
      human myometrium. CONCLUSION(S): These findings open up new possibilities for
      understanding the origin of this benign tumor and help to develop new nonsurgical
      approaches for their management.

PMID- 24890272
TI  - Introduction: are we ready to eliminate the transfer of fresh embryos in in vitro
      fertilization?
AB  - The rationale to freeze all embryos to avoid transfer into a supraphysiologic
      environment to improve safety and efficacy is compelling, but not yet proven. How
      do we decide? 

PMID- 24890267
TI  - Fluorescence- and magnetic-activated cell sorting strategies to isolate and
      enrich human spermatogonial stem cells.
AB  - OBJECTIVE: To determine the molecular characteristics of human spermatogonia and
      optimize methods to enrich spermatogonial stem cells (SSCs). DESIGN: Laboratory
      study using human tissues. SETTING: Research institute. PATIENT(S): Healthy adult
      human testicular tissue. INTERVENTION(S): Human testicular tissue was fixed or
      digested with enzymes to produce a cell suspension. Human testis cells were
      fractionated by fluorescence-activated cell sorting (FACS) and magnetic-activated
      cell sorting (MACS). MAIN OUTCOME MEASURE(S): Immunostaining for selected
      markers, human-to-nude mouse xenotransplantation assay. RESULT(S):
      Immunohistochemistry costaining revealed the relative expression patterns of
      SALL4, UTF1, ZBTB16, UCHL1, and ENO2 in human undifferentiated spermatogonia as
      well as the extent of overlap with the differentiation marker KIT. Whole mount
      analyses revealed that human undifferentiated spermatogonia (UCHL1+) were
      typically arranged in clones of one to four cells whereas differentiated
      spermatogonia (KIT+) were typically arranged in clones of eight or more cells.
      The ratio of undifferentiated-to-differentiated spermatogonia is greater in
      humans than in rodents. The SSC colonizing activity was enriched in the THY1dim
      and ITGA6+ fractions of human testes sorted by FACS. ITGA6 was effective for
      sorting human SSCs by MACS; THY1 and EPCAM were not. CONCLUSION(S): Human
      spermatogonial differentiation correlates with increased clone size and onset of
      KIT expression, similar to rodents. The undifferentiated-to-differentiated
      developmental dynamics in human spermatogonia is different than rodents. THY1,
      ITGA6, and EPCAM can be used to enrich human SSC colonizing activity by FACS, but
      only ITGA6 is amenable to high throughput sorting by MACS.

PMID- 24890273
TI  - Has noninvasive fetal trisomy testing (NIFTY) rung the death knell for other
      forms of prenatal testing?

PMID- 24890271
TI  - Polymorphisms in vitamin D-related genes and risk of uterine leiomyomata.
AB  - OBJECTIVE: To investigate uterine leiomyomata (UL) incidence in relation to
      polymorphisms in genes involved in vitamin D metabolism and skin pigmentation.
      Rates of UL are 2-3 times higher in African Americans than in European Americans.
      Recent studies suggest that vitamin D deficiency is associated with an increased
      risk of UL. DESIGN: Nested case-control study. SETTING: Not applicable.
      PATIENT(S): Two thousand two hundred thirty-two premenopausal women first
      diagnosed with UL confirmed by ultrasound or surgery during 1997-2011 (cases) and
      2,432 premenopausal women never diagnosed with UL through 2011 (controls).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Self-reported UL. We used
      logistic regression to estimate odds ratios (OR) and 95% confidence intervals
      (CI) for the association between each polymorphism and UL, controlling for age,
      geographic region, and ancestry. RESULT(S): Three of 12 polymorphisms were
      associated with UL at the nominal significance level: rs4944957 and rs12800438
      near DHCR7 and rs6058017 in ASIP. After correction for multiple hypothesis
      testing, two single nucleotide polymorphisms remained significantly associated
      with UL (rs12800438 and rs6058017). Compared with the AA genotype for rs12800438
      (correlated with higher serum 25[OH]D levels), ORs were 1.09 (95% CI, 0.92, 1.29)
      and 1.23 (95% CI, 1.03, 1.47) for the GA and GG genotypes, respectively. Compared
      with the AA genotype for rs6058017 (correlated with lighter skin pigmentation),
      ORs were 1.01 (95% CI, 0.83, 1.22) and 1.18 (95% CI, 0.97, 1.44) for the GA and
      GG genotypes, respectively. CONCLUSION(S): Our data support the hypothesis that
      vitamin D deficiency is involved in UL etiology.

PMID- 24890276
TI  - 7-Aryl-7-deazaadenine 2'-deoxyribonucleoside triphosphates (dNTPs): better
      substrates for DNA polymerases than dATP in competitive incorporations.
AB  - A series of 7-substituted 7-deazaadenine and 5-substituted cytosine 2'
      deoxyribonucleoside triphosphates (dNTPs) were tested for their competitive
      incorporations (in the presence of dATP and dCTP) into DNA by several DNA
      polymerases by using analysis based on cleavage by restriction endonucleases. 7
      Aryl-7-deazaadenine dNTPs were more efficient substrates than dATP because of
      their higher affinity for the active site of the enzyme, as proved by kinetic
      measurements and calculations. 

PMID- 24890275
TI  - Cryopreservation of human embryos and its contribution to in vitro fertilization
      success rates.
AB  - Cryopreservation of human embryos is now a routine procedure in assisted
      reproductive technologies laboratories. There is no consensus on the superiority
      of any protocol, and substantial differences exist among centers in day of embryo
      cryopreservation, freezing method, selection criteria for which embryos to
      freeze, method of embryo thawing, and endometrial preparation for transfer of
      frozen-thawed embryos. In the past decade, the number of frozen-thawed embryo
      transfer cycles per started in vitro fertilization (IVF) cycle increased
      steadily, and at the same time the percentage of frozen-thawed embryo transfers
      that resulted in live births increased. Currently, cryopreservation of human
      embryos is more important than ever for the cumulative pregnancy rate after IVF.
      Interestingly, success rates after frozen-thawed embryo transfer are now nearing
      the success rates of fresh embryo transfer. This supports the hypothesis of so
      called freeze-all strategies in IVF, in which all embryos are frozen and no fresh
      transfer is conducted, to optimize success rates. High-quality randomized
      controlled trials should be pursued to find out which cryopreservation protocol
      is best and whether the time has come to completely abandon fresh transfers. 

PMID- 24890277
TI  - Thermally driven polymorphic transition prompting a naked-eye-detectable bending
      and straightening motion of single crystals.
AB  - The amplification of molecular motions so that they can be detected by the naked
      eye (10(7) -fold amplification from the angstrom to the millimeter scale) is a
      challenging issue in the development of mechanical molecular devices. In this
      context, the perfectly ordered molecular alignment of the crystalline phase has
      advantages, as demonstrated by the macroscale mechanical motions of single
      crystals upon the photochemical transformation of molecules. In the course of our
      studies on thermoresponsive amphiphiles containing tetra(ethylene glycol) (TEG)
      moieties, we serendipitously found that thermal conformational changes of TEG
      units trigger a single-crystal-to-single-crystal polymorphic phase transition.
      The single crystal of the amphiphile undergoes bending and straightening motion
      during both heating and cooling processes at the phase-transition temperatures.
      Thus, the thermally triggered conformational change of PEG units may have the
      advantage of inducing mechanical motion in bulk materials. 

PMID- 24890274
TI  - Why we should transfer frozen instead of fresh embryos: the translational
      rationale.
AB  - Epidemiologic studies have shown an increased rate of adverse perinatal outcomes,
      including small for gestational age (SGA) births, in fresh in vitro fertilization
      (IVF) cycles compared with frozen embryo transfer cycles. This increase is not
      seen in the donor oocyte population, suggesting that it is the peri-implantation
      environment created after superovulation that is responsible for these changes.
      During a fresh IVF cycle, multiple corpora lutea secrete high levels of hormones
      and other factors that can affect the endometrium and the implanting embryo. In
      this review, we discuss both animal and human data demonstrating that
      superovulation has significant effects on the endometrium and embryo.
      Additionally, potential mechanisms for the adverse effects of gonadotropin
      stimulation on implantation and placental development are proposed. We think that
      these data, along with the growing body of epidemiologic evidence, support the
      proposal that frozen embryo transfer should be considered preferentially,
      particularly in high responders, as a means to potentially decrease at least some
      of the adverse perinatal outcomes associated with IVF. 

PMID- 24890278
TI  - Ring expansion of cyclic 1,2-diols to form medium sized rings via ruthenium
      catalyzed transfer hydrogenative [4+2] cycloaddition.
AB  - A new method for the ring expansion of cyclic diols is described. Using improved
      conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with
      1,3-dienes, fused [n.4.0] bicycles (n = 3-6) are formed, which upon exposure to
      iodosobenzene diacetate engage in oxidative cleavage to form the 9-12 membered
      rings . 

PMID- 24890279
TI  - Upper gastrointestinal motility: prenatal development and problems in infancy.
AB  - Deglutition, or swallowing, refers to the process of propulsion of a food bolus
      from the mouth into the stomach and involves the highly coordinated interplay of
      swallowing and breathing. At 34 weeks gestational age most neonates are capable
      of successful oral feeding if born at this time; however, the maturation of
      respiration is still in progress at this stage. Infants can experience congenital
      and developmental pharyngeal and/or gastrointestinal motility disorders, which
      might manifest clinically as gastro-oesophageal reflux (GER) symptoms, feeding
      difficulties and/or refusal, choking episodes and airway changes secondary to
      micro or overt aspiration. These problems might lead to impaired nutritional
      intake and failure to thrive. These gastrointestinal motility disorders are
      mostly classified according to the phase of swallowing in which they occur, that
      is, the oral preparatory, oral, pharyngeal and oesophageal phases. GER is a
      common phenomenon in infancy and is referred to as GERD when it causes
      troublesome complications. GER is predominantly caused by transient relaxation of
      the lower oesophageal sphincter. In oesophageal atresia, oesophageal motility
      disorders develop in almost all patients after surgery; however, a congenital
      origin of disordered motility has also been proposed. This Review highlights the
      prenatal development of upper gastrointestinal motility and describes the most
      common motility disorders that occur in early infancy. 

PMID- 24890280
TI  - Colorectal cancer: chemopreventive action of synthetic triterpenoids in CRC.

PMID- 24890281
TI  - Faecal incontinence: NASHA Dx injection therapy shows long-term efficacy for
      faecal incontinence.

PMID- 24890282
TI  - Liver: loss of integrin beta1 impairs liver regeneration and HCC progression.

PMID- 24890283
TI  - Family history, body mass index and survival in Japanese patients with stomach
      cancer: a prospective study.
AB  - Family history and nutritional status may affect the long-term prognosis of
      stomach cancer, but evidence is insufficient and inconsistent. To clarify the
      prognostic factors of stomach cancer, we conducted a prospective study of 1,033
      Japanese patients with histologically confirmed stomach cancer who were admitted
      to a single hospital between 1997 and 2005. Family history of stomach cancer and
      pretreatment body mass index (BMI) were assessed using a self-administered
      questionnaire. Clinical data were retrieved from a hospital-based cancer
      registry. All patients were completely followed up until December, 2008. Hazard
      ratios (HRs) and 95% confidence intervals (CIs) were estimated according to
      family history in parents and siblings and BMI category. During a median follow
      up of 5.3 years, 403 all-cause and 279 stomach cancer deaths were documented.
      Although no association with family history was observed in the patients overall,
      analysis according to age group found an increased risk of all-cause death
      associated with a history in first degree relatives (HR = 1.61, 95% CI: 0.93
      2.78, p = 0.09) and with a parental history (HR = 1.86, 95% CI: 1.06-3.26) among
      patients aged under 60 years at diagnosis. BMI was related to all-cause and
      stomach cancer death among patients aged 60 and over, showing a J-shaped pattern
      (HR of all-cause death = 2.28 for BMI < 18.5; HR = 1.61 for 25 <= vs. >= 23.0 to
      < 25.0 kg/m(2)). A family history of stomach cancer, especially parental history,
      may affect mortality among younger stomach cancer patients, whereas nutritional
      status may be a prognostic factor in older patients.

PMID- 24890284
TI  - Role of molecular properties of ulvans on their ability to elaborate antiadhesive
      surfaces.
AB  - Antiadhesive properties of polysaccharides (such ulvans) once immobilized on a
      surface are described in the literature but the parameters governing their
      antifouling properties are not yet well identified. In the present study, the
      relationship between molecular parameters of ulvans and the inhibition of
      bacterial adhesion was investigated. To this aim, various ulvans were grafted on
      silicon wafers under two different experimental immobilization conditions.
      Results showed that the experimental immobilization conditions and the
      polysaccharides molecular weight led to specific layer conformations which
      exhibited a key role in the surface antiadhesive properties.

PMID- 24890285
TI  - Conflict of roles: a conflict of ideas? The unsettled relations between care team
      staff and independent mental health advocates.
AB  - Drawing on a national study of independent mental health advocacy, we explored
      the social relations of independent advocacy. The study was commissioned by the
      Department of Health (England), and involved a case study design covering eight
      different geographies and service configurations, and interviews or focus groups
      with a total of 289 stakeholders across two phases of inquiry. This paper focused
      on the analysis of qualitative data relevant to the relationship between mental
      health-care services and independent advocacy services, drawn from interviews
      with 214 participants in phase two of the study. Discussion of these particular
      findings affords insights into the working relations of independent advocacy
      within mental health services beset by reorganizational change and funding cuts,
      and increasing levels of legally-sanctioned compulsion and coercion. We offer a
      matrix, which accounts for the different types of working relationships that can
      arise, and how these are associated with various levels of understanding of
      independent advocacy and appreciation for the value of advocacy. The discussion
      is framed by the wider literature on advocacy and the claims by practitioners,
      such as nurses, for an advocacy role as part of their professional repertoire. 

PMID- 24890286
TI  - Frequent activating HRAS mutations in trichilemmoma.
AB  - BACKGROUND: Trichilemmoma is a benign follicular epithelial tumour exhibiting
      outer root sheath differentiation. It is associated with Cowden syndrome and
      naevus sebaceus (NS), but the pathogenesis of sporadic tumours is poorly
      understood. Recently, NS was found to be caused by postzygotic HRAS or KRAS
      mutations. OBJECTIVES: We sought to determine whether NS-related and NS-unrelated
      trichilemmomas harbour RAS mutations. METHODS: Formalin-fixed and paraffin
      embedded blocks of 12 NS-related and 15 NS-unrelated trichilemmomas from 26
      individuals were retrieved and analysed to determine the presence of mutations in
      exons 1 and 2 of the HRAS, KRAS and NRAS genes by polymerase chain reaction and
      direct sequencing. Mutational hotspots of the FGFR3 and PIK3CA genes were also
      analysed for NS-unrelated cases. RESULTS: Among the 27 cases, mutually exclusive
      HRAS c.37G>C and c.182A>G mutations were observed in 17 and three tumours,
      respectively. Of the 12 NS-related tumours, 11 (92%) harboured the HRAS c.37G>C
      substitution. Of the 15 sporadic tumours, nine (60%) harboured HRAS mutations,
      including six c.37G>C and three c.182A>G. An HRAS c.182A>G mutation was observed
      only in sporadic tumours. No mutations were observed in the other genes that were
      tested. CONCLUSIONS: The high frequency of HRAS activating mutations, including
      the c.182A>G substitution, which was rather rare in NS, suggests that most
      trichilemmomas are authentic neoplasms.

PMID- 24890287
TI  - Endothelium-dependent vasodilation predicts the development of the metabolic
      syndrome.
AB  - BACKGROUND: Different techniques to evaluate endothelium-dependent vasodilation
      (EDV) in resistance and conduit arteries have been described and have been
      associated with the occurrence of the metabolic syndrome (MetS) in cross
      sectional studies. This study aimed to evaluate whether EDV in resistance and
      conduit arteries could predict future development of the MetS in the Prospective
      Study of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS: In the
      population-based PIVUS study (1016 subjects all aged 70 at baseline), the
      invasive forearm technique with acetylcholine given in the brachial artery
      (resistance arteries, EDV) and the brachial artery ultrasound technique with the
      measurement of flow-mediated dilatation (conduit artery, FMD) were evaluated. Six
      hundred and twenty-four subjects free of the MetS (NCEP/ATPIII criteria) at the
      age of 70 were reinvestigated at the age of 75. RESULTS: During the 5-year follow
      up, 109 new subjects developed the MetS. EDV, but not FMD, predicted the
      development of the MetS (OR 0.78 for a 1 SD increase in EDV, 95%CI 0.62-0.97, P =
      0.033). Of the five components of the MetS, EDV could significantly predict the
      development of the glucose (P = 0.02), waist circumference (P = 0.01) and the
      triglyceride components (P = 0.002), but not significantly so the HDL (P = 0.09)
      and blood pressure components (P = 0.92). CONCLUSIONS: EDV in resistance
      arteries, but not in the brachial conduit artery (FMD), was a predictor of future
      development of the MetS, mainly by prediction of future impairments in fasting
      glucose, serum triglycerides and waist circumference in an elderly cohort.

PMID- 24890288
TI  - Spine interbody implants: material selection and modification, functionalization
      and bioactivation of surfaces to improve osseointegration.
AB  - The clinical outcome of lumbar spinal fusion is correlated with achievement of
      bony fusion. Improving interbody implant bone on-growth and in-growth may enhance
      fusion, limiting pseudoarthrosis, stress shielding, subsidence and implant
      failure. Polyetheretherketone (PEEK) and titanium (Ti) are commonly selected for
      interbody spacer construction. Although these materials have desirable
      biocompatibility and mechanical properties, they require further modification to
      support osseointegration. Reports of extensive research on this topic are
      available in biomaterial-centric published reports; however, there are few
      clinical studies concerning surface modification of interbody spinal implants.
      The current article focuses on surface modifications aimed at fostering
      osseointegration from a clinician's point of view. Surface modification of Ti by
      creating rougher surfaces, modifying its surface topography (macro and nano),
      physical and chemical treatment and creating a porous material with high
      interconnectivity can improve its osseointegrative potential and bioactivity.
      Coating the surface with osteoconductive materials like hydroxyapatite (HA) can
      improve osseointegration. Because PEEK spacers are relatively inert, creating a
      composite by adding Ti or osteoconductive materials like HA can improve
      osseointegration. In addition, PEEK may be coated with Ti, effectively bio
      activating the coating. 

PMID- 24890289
TI  - Cricket injuries: an orthopaedist's perspective.
AB  - A decade ago, cricket has traditionally been regarded as relatively injury free,
      although it has been classified as having a "moderate" injury risk. At present,
      cricket has evolved into shorter and more competitive versions involving greater
      aggression and often played for long periods of time. This has expectedly ensued
      in an increase in the number of cricketing injuries similar to those seen in
      other sports which involve running, throwing, or being hit by a hard object.
      However, there are some injuries to look out for especially in cricket players.
      In this article, we have reviewed information about cricket injuries that will
      help orthopaedists make the correct diagnoses and initiate appropriate treatment.
      Orthopaedic surgeons and physiotherapists should work as a team to detect
      treatable cricket injuries at an early stage and ensure that every precaution is
      taken to minimize the risks of injury. 

PMID- 24890290
TI  - Three-dimensional computerized preoperative planning of total hip arthroplasty
      with high-riding dislocation developmental dysplasia of the hip.
AB  - OBJECTIVE: To assess whether computed tomography (CT)-based 3-dimensional (3D)
      computerized pre-operative planning is accurate and reliable in patients with
      high-riding dislocation developmental dysplasia of the hip (DDH) undergoing total
      hip arthroplasty (THA). METHODS: Between September 2009 and February 2011, a
      prospective study with an inbuilt means of comparing predictive techniques in 20
      patients (20 hips) with high-riding dislocation DDH was undertaken. All patients
      had pre- and post-operative CT scans, data from which were transferred digitally
      to Mimics software. 3D pre-operative planning to predict the acetabular component
      size, hip rotation center position and acetabular component coverage was
      performed using Mimics software. The results and post-operative course were
      compared with those of the traditional acetate templating technique. RESULTS:
      Using 3D computerized planning, 14/20 components (70%) were predicted exactly and
      6/20 (30%) within one size, whereas with the conventional acetate templating
      technique, 5/20 components (25%) were predicted exactly, 9/20 (45%) within one
      size and 6/20 (30%) within two or more sizes. There was a strong correlation
      between the 3D computerized planned acetabular component size, hip rotation
      center distance, acetabular component host coverage and that found
      postoperatively. Five patients were considered to need structural bone graft on
      the basis of 3D computerized planning; this was highly coincident with the
      intraoperative findings in all five cases. CONCLUSION: CT-based 3D computerized
      pre-operative planning using Mimics software is an accurate and reliable
      technique for patients with high-riding dislocation DDH undergoing THA.

PMID- 24890291
TI  - Extensively coated non-modular stem used in two-stage revision for infected total
      hip arthroplasty: mid-term to long-term follow-up.
AB  - OBJECTIVE: To determine the rate of curing the infection and mid- to long-term
      outcomes of using extensively coated non-modular stems in two-stage revision for
      infected total hip arthroplasty (THA). METHODS: The clinical data of 33 patients
      (33 hips) in whom extensively coated non-modular stems had been used in two-stage
      revision THA for deep infection were retrospectively analyzed. All operations
      received two-stage reimplantation, which included resection arthroplasty,
      thorough debridement, insertion of a hand-molded antibiotic-impregnated cement
      spacer with stainless steel reinforcement, a course of intravenous antibiotics,
      and delayed reimplantation. Microorganism-specific antibiotics had been chosen
      according to the results of microbiological studies performed postoperatively.
      All patients received i.v. antimicrobial therapy for 4 weeks and oral antibiotics
      to which their organisms were sensitive for a further 6 weeks. Harris hip score
      (HHS) and plain X-ray films were used to perform clinical and radiological
      evaluations. RESULTS: During follow-up for a minimum of 5 years, no reinfection
      or loosening were found. Cultures of samples taken during the second stage were
      all negative for infection. The mean HHS improved from 42 preoperative to 89 at
      the final follow-up. All granular bones had fused well with the host bones by 12
      months after the surgery. CONCLUSION: Using extensively coated non-modular stems
      combined with intramedullary allografts in two-stage revision for treating
      infected THAs can achieve satisfactory outcomes.

PMID- 24890292
TI  - Combination of percutaneous unilateral translaminar facet screw fixation and
      interbody fusion for treatment of lower lumbar vertebra diseases: a follow-up
      study.
AB  - OBJECTIVE: To investigate the feasibility and efficacy of sight-guided
      percutaneous unilateral translaminar facet screw fixation (TLFSF) with interbody
      fusion for treatment of lower lumbar vertebra diseases. METHODS: Twenty-nine
      adult patients with lower lumbar disease underwent sight-guided percutaneous
      unilateral TLFSF combined with microsurgical spinal decompression, discectomy,
      and interbody fusion from June 2007 to June 2008. All 29 patients had low back
      pain caused by lumbar disc degeneration (20 cases), in situ recurrent lumbar disc
      herniation (2), primary diskitis (1), lumbar disc herniation with spinal stenosis
      (3), and first-degree lumbar degenerative spondylolisthesis (3). Twenty-three
      cases had lesions at L4,5 ; three at L5 S1 , one at L3,4 , L4,5 , and two at L4,5
      , L5 S1 . RESULTS: No patient experienced significant postoperative
      complications. The mean incision length was 4.48 +/- 0.55 cm; operative time 1.34
      +/- 0.22 h; intraoperative blood loss 280 +/- 175 mL; and postoperative drainage
      volume 165 +/- 85 mL. Screw position results: type I, 21 cases (23 segments);
      type II, 7 cases (8 segments); and type III, 1 case (1 segment). Twenty-eight
      patients were followed up for 24-60 months (average, 47.5 months). Interbody
      fusion rate was 93.5%). Postoperative intervertebral height recovered
      significantly; however, loss of intervertebral height occurred during follow-up.
      CONCLUSION: Sight-guided percutaneous unilateral TLFSF with interbody fusion for
      treatment of lower lumbar disease is simple and minimally invasive, with good
      screw accuracy and security, high fusion rate, and good efficacy. However,
      specific surgical indications must be strictly followed.

PMID- 24890293
TI  - What is the rate of lumbar adjacent segment disease after percutaneous versus
      open fusion?
AB  - OBJECTIVE: Adjacent segment disease (ASD) requiring treatment or re-operation is
      a common problem after surgery on the lumbar spine. The hypothesis of this
      retrospective study was that ASD occurs less often following lumbar spine fusion
      in patients who undergo percutaneous minimally invasive (MIS) instrumentation
      than in those in whom open instrumentation is used. METHODS: A case-control study
      was performed on consecutive patients who had undergone staged single or two
      level anterior lumbar interbody fusion for degenerative conditions followed by
      open or MIS instrumentation from 2002 to 2005 in our institution. ASD was defined
      as that necessitating additional procedures for new symptoms related to an
      adjacent lumbar dermatome. RESULTS: One hundred and seventeen patients met the
      inclusion criteria. Of these, 53 had been followed up by chart or medical record
      review for longer than one year. There were 23 patients in the MIS group and 30
      in the open group. Of the 30 patients in the open group, 9 had developed ASD
      (30%). Of the 23 patients in the MIS group, 7 had developed ASD (30%). This
      difference is not statistically significant (P = 1.00). CONCLUSION: Contrary to
      our hypothesis, there was no significant difference in incidence of ASD in
      patients who had underwent open versus percutaneous instrumentation following
      anterior lumbar interbody fusion.

PMID- 24890294
TI  - Minimally invasive treatment of clavicular fractures with cannulated screw.
AB  - OBJECTIVE: To evaluate minimally invasive treatment of clavicular fractures with
      cannulated screw. METHODS: Data of 65 patients who had undergone minimally
      invasive treatment with cannulated screws for clavicular fractures from April
      2009 to October 2010 were retrospectively analyzed and compared with those of 65
      patients with clavicular fractures who had been treated by the same surgeons with
      plates. In the study group, there were 41 males and 24 females, aged from 19-67
      years (mean, 35.8 years). According to Craig's classification, there were 29
      group 1 and 36 of group 2-II. Neer scores were used to evaluate shoulder function
      and radiographs to assess fracture union. RESULTS: The incision length was 4-5 cm
      in the cannulated screw group (CSG) and 10-11 cm in the reconstructive plate
      group (RPG). Radiographs showed bone union was achieved in both groups, the bone
      healing time being 13.2 +/- 6.9 weeks in the CSG and 16.3 +/- 8.7 weeks in the
      RPG. All patients were followed up for 6 to 20 months (average, 10.6 months). The
      average Neer score was 96.6 +/- 3.4 in the CSG and 94.2 +/- 5.8 in the RPG. In
      the CSG, screw loosening occurred in five, and fracture displacement in three.
      There was a significant difference in fracture healing time between two groups
      but not in Neer score. CONCLUSION: Minimally invasive treatment of clavicular
      fractures with cannulated screws has the advantages of minimal invasion, short
      bone healing time, good clinical outcomes, and being relatively inexpensive.

PMID- 24890295
TI  - Biomechanical analysis of four types of internal fixation in subtrochanteric
      fracture models.
AB  - OBJECTIVE: To compare the biomechanical properties of four types of internal
      fixation (proximal femoral nail [PFN], dynamic hip screw [DHS], dynamic condylar
      screw [DCS], and proximal femoral locking plate [PFLP]) for different types of
      subtrochanteric fractures. METHODS: Thirty-two antiseptic femurs were randomly
      divided into four groups. After internal fixation had been implanted, different
      types of subtrochanteric fracture models were produced and each tested under
      vertical, torsional and vertical damage loads. RESULTS: The stiffness ratio of
      PFN in each fracture model and failure load were the highest in the four groups;
      however, the torsional stiffness ratio was the lowest. Tension strain ratios of
      DHS and DCS on the lateral side became compression strain ratios with restoration
      of the medial fragment. The stiffness ratio of DHS was lower than PFLP in each
      fracture model, torsional stiffness ratio was the highest in fracture models II
      to V and the failure load was lower only than PFN. The stiffness ratio and
      failure load of DCS were both the lowest, torsional stiffness ratio was similar
      to PFLP's in fracture models II to V. The stiffness ratio of PFLP was only lower
      than PFN's in each fracture model, but the failure load was lower than DHS's.
      CONCLUSION: Four types of internal fixation achieve better stabilities for type I
      subtrochanteric fractures. PFN and PFLP produce reliable stability in type IIIA
      subtrochanteric fractures. If the medial buttress is restored, DCS can be
      considered. For type IV subtrochanteric fractures, only PFN provides stable
      fixation. PFLP is suitable for comminuted fractures with large fragments.

PMID- 24890296
TI  - Femoral stress and strain changes post-hip, -knee and -ipsilateral hip/knee
      arthroplasties: a finite element analysis.
AB  - OBJECTIVE: To identify the optimal ratio of free femur for minimizing the risks
      of periprosthetic fracture. METHODS: Three dimensional models of the femur with
      hip and knee stem elongation were constructed. With the distal femoral condylar
      surface fixed in a three dimensional model, the femoral head loading was
      performed according to the methods described by Huiskes and van Rietbergen in the
      models of hip replacement, knee replacement with or without hip stem or knee stem
      elongation. The maximum principal stress (MPS) and maximum principal elastic
      strain (MPES) of the femur were recorded and their relationships to the free
      femur ratio were analyzed using Pearson's correlation analysis. RESULTS: There
      were no obvious changes in MPS and MPES with hip stem elongation from 100 to 180
      mm. In ipsilateral hip and knee replacement, the MPS and MPES had a tendency to
      decrease with knee and hip stem elongation. The MPS and MPES were mainly located
      in the anterior medial side of the middle to distal femur post-hip replacement
      and distalized with stem elongation. When the knee stem had been elongated more
      than 120 mm, the stress and strain concentrated strongly in the middle of the
      femoral shaft. There was a positive correlation between MPS and MPES to the free
      femur ratio (P < 0.01); however, no optimal ratio of free femur that would
      minimize the risks of periprosthetic fracture was identified. CONCLUSION:
      Positive correlations were found between implant free femur and stress and strain
      changes in total knee arthroplasty, total hip arthroplasty and ipsilateral hip
      and knee replacement.

PMID- 24890297
TI  - Tumor-to-background ratio to predict response to chemotherapy of osteosarcoma
      better than standard uptake values.
AB  - OBJECTIVE: According to the current treatment protocol of the Cooperative
      Osteosarcoma Study, it is mandatory to determine the histological response to
      neoadjuvant chemotherapy treatment before surgical removal of the tumor,
      particularly if a limb salvage procedure is planned. The aim of this systematic,
      retrospective study was to evaluate the ability of 2-((18) F) fluoro-2-deoxy-D
      glucose positron-emission tomography/computed tomography to predict chemotherapy
      response of osteosarcoma and to identify a simple promising method for
      noninvasive evaluation of neoadjuvant chemotherapy response in osteosarcoma.
      METHODS: The PubMed database was searched to identify and analyze relevant
      published reports. In particular, correlations between tumor-to-background ratio
      (TBR), standard uptake value (SUV) and histological response to chemotherapy were
      assessed. RESULTS: It was found that good responses are achieved in patients with
      TBR after chemotherapy (TBR2)/TBR before chemotherapy (TBR1) < 0.470 (positive
      predictive value [PPV] = 92.31%, negative predictive value [NPV] = 82.76%,
      sensitivity [S] = 87.80%, specificity [SP] = 88.89%), whereas poor responses
      occur in patients with SUV after chemotherapy/before chemotherapy (SUV2/SUV1) >
      0.396 (PPV = 73.68%, NPV = 73.33%, S = 63.64%, SP = 81.48%). CONCLUSION: Changes
      in TBR are better predictors of chemotherapy response than SUV in osteosarcoma
      patients. Therefore, we believe that choice of surgical strategy is optimally
      based on changes in TBR.

PMID- 24890298
TI  - Staged treatment of proximal tibial fracture using external locking compression
      plate.
AB  - OBJECTIVE: To share our preliminary clinical success and failure with using an
      external locking compression plate (LCP) for proximal tibial fractures, further
      refine the indications for this procedure and review relevant published reports.
      METHODS: The current study reports two cases of proximal tibial fracture treated
      with external LCP as the second stage of a two-stage treatment. One patient was a
      59-year-old man with a closed proximal tibial/fibular fracture caused by falling
      on ice while getting out of his car, and another patient was a 42-year-old male
      smoker with right comminuted proximal tibia, tibial plateau and proximal fibular
      fractures. The outcomes were evaluated by radiographs and weight bearing status.
      RESULTS: In the first case, the fracture healed uneventfully whereas the second
      case required further open-reduction with internal fixation because correct
      alignment could not be achieved with an external LCP. CONCLUSION: Correct
      alignment of proximal tibial fractures followed by use of an external LCP can
      achieve favorable outcomes.

PMID- 24890299
TI  - Diagnosis of pharyngeal fistula by video laryngoscopy and its nonsurgical
      treatment: a case report.

PMID- 24890300
TI  - Neonatal radial nerve palsy associated with humerus fracture: is the fracture to
      be blamed?

PMID- 24890301
TI  - Total hip arthroplasty via lateral approach in supine position.

PMID- 24890302
TI  - Lumbar discectomy for lumbar disc herniation.

PMID- 24890303
TI  - Enchondroma of the nasal septum due to Ollier disease: a case report and review
      of the literature.
AB  - BACKGROUND: Morbus Ollier is characterized by the presence of multiple
      enchondromas (ie, benign intraosseous cartilaginous lesions). Although their
      manifestation in the limb bones is well described, only a few cases with ear,
      nose, and throat (ENT) involvement, primarily arising from the skull, have been
      reported. The malignant transformation toward slowly growing low-grade
      chondrosarcomas is the most severe form of progression. METHODS: We report a
      unique case of a 54-year-old patient with Ollier disease with an extensive nasal
      enchondroma apparently eroding the middle nasal concha and expanding to the
      lateral nasal wall that raised suspicion of malignant transformation. RESULTS:
      Radiological and histological features of enchondromas can be controversial and
      seem to have limited sensitivity to exclude low-grade malignancy. The clinical
      symptoms play a decisive role in differentiation between enchondromas and low
      grade chondrosarcomas. CONCLUSION: Surgery remains the only effective solution in
      removing an enchondroma and preventing the tendency toward malignant
      transformation.

PMID- 24890305
TI  - The challenge of improving outcomes for patients with CF sinonasal disease.

PMID- 24890304
TI  - Effect of high dose isoflurane on cerebral blood flow in macaque monkeys.
AB  - The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated
      in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous
      arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of
      isoflurane resulted in significant increase in the mean CBF of the global,
      cortical, subcortical regions and the regional CBF in all subcortical structures
      and most cortical structures (such as motor cortex, anterior cingulate cortex,
      but not media prefrontal cortex). In addition, the changes of regional CBF in the
      affected regions correlated linearly with increasing isoflurane concentrations.
      The study demonstrates region-specific CBF abnormal increase in adult macaque
      monkeys under high dose (2%) isoflurane and suggests that the brain functionality
      in the corresponding structures may be affected and need to be taken
      consideration in either human or non-human primate neuroimaging studies. 

PMID- 24890306
TI  - The influence of age on the thresholds of compensatory stepping and dynamic
      stability maintenance.
AB  - The purpose of this study was to investigate the effects of age on compensatory
      stepping thresholds and dynamic stability maintenance in response to postural
      disturbances. It was hypothesized that, with older age, anterior but not
      posterior stepping thresholds would be reduced. Thirteen young adults (31.1 +/-
      0.8 years), 11 middle-aged adults (57.6 +/- 2.5 years), and 11 older adults (73.8
      +/- 5.3 years) participated in this study. Surface translations were delivered as
      subjects stood on a microprocessor-controlled treadmill. Subjects were instructed
      to "try not to step". Stepping thresholds were defined as the largest
      displacement at a given peak treadmill-belt velocity for which a subject could
      prevent stepping. The margin of stability was calculated to estimate the minimum
      dynamic stability at the stepping thresholds. Age-related declines in the ability
      to prevent forward steps were apparent. Anterior stepping thresholds were reduced
      with age. The minimum margin of stability associated with anterior stepping
      thresholds was not influenced by age. Therefore, smaller disturbance
      displacements caused middle-aged and older subjects to become dynamically
      unstable to the point of stepping. Posterior stepping thresholds were not
      influenced by age. It is concluded that an age-related decline in anterior, but
      not posterior, stepping thresholds was due to an impaired ability to maintain
      dynamic stability after a disturbance.

PMID- 24890307
TI  - Effects of footwear on treadmill running biomechanics in preadolescent children.
AB  - While recent research debates the topic of natural running in adolescents and
      adults, little is known about the influence of footwear on running patterns in
      children. The purpose of this study was to compare shod and barefoot running gait
      biomechanics in preadolescent children. Kinematic and ground reaction force data
      of 36 normally developed children aged 6-9 years were collected during running on
      an instrumented treadmill. Running conditions were randomized for each child in
      order to compare barefoot running with two different shod conditions: a cushioned
      and a minimalistic running shoe. Primary outcome was the ankle angle at foot
      strike. Secondary outcomes were knee angle, maximum and impact ground reaction
      forces, presence of rear-foot strike, step width, step length and cadence. Ankle
      angle at foot strike differed with statistical significance (p < 0.001) between
      conditions. Running barefoot reduced the ankle angle at foot strike by 5.97
      degrees  [95% CI, 4.19; 7.75] for 8 kmh(-1) and 6.18 degrees  [95% CI, 4.38;
      7.97] for 10 kmh(-1) compared to the cushioned shoe condition. Compared to the
      minimalistic shoe condition, running barefoot reduced the angle by 1.94 degrees 
      [95% CI, 0.19 degrees ; 3.69 degrees ] for 8 kmh(-1) and 1.38 degrees  [95% CI, 
      3.14 degrees ; 0.39 degrees ] for 10 kmh(-1). Additionally, using footwear
      significantly increased maximum and impact ground reaction forces, step length,
      step width and rate of rear-foot strike. In conclusion, preadolescent running
      biomechanics are influenced by footwear, especially by cushioned running shoes.
      Health professionals and parents should keep this in mind when considering
      footwear for children.

PMID- 24890308
TI  - Effect of vascular seal configuration using the LigaSure on arterial challenge
      pressure, time for seal creation, and histologic features.
AB  - OBJECTIVE: To determine the effectiveness of a vascular sealing technology on
      canine carotid arteries using various seal configurations to achieve maximal
      vessel security. STUDY DESIGN: Ex-vivo study. ANIMALS: Dogs (n = 20). METHODS:
      Carotid arteries (n = 40) were removed from the mid-cervical region of recently
      euthanatized dogs. Harvested vessels were closed with 2 circumferential ligatures
      (Group 1) or a vascular sealing device using 1 of 4 seal configurations of 1 or 2
      seals combined with 1 or 2 machine activations/seal. The artery was instrumented
      to measure intraluminal pressure to evaluate the security of each seal during
      saline infusion. Maximum intraluminal pressure was recorded for each group, and
      time for application of each sealing protocol was compared using 1-way ANOVA and
      Tukey's test for multiple comparisons. Histologic features of the sealing
      protocols were evaluated. RESULTS: Arterial closures for each group were
      effective in preventing leakage up to 300 mmHg. There was no significant
      difference in maximum intraluminal pressure between any group. A significant
      difference (P <= .001) was observed for time to seal creation between the groups
      using 1 and 2 seals. Histologic evaluation showed no differences between the
      different sealing protocols. CONCLUSION: Vessel sealing using a single seal
      created with a single activation cycle was adequate for sealing canine carotid
      arteries. Histologic examination did not demonstrate any disadvantages to
      multiple seals or multiple cycle activations.

PMID- 24890309
TI  - Identity-by-descent approaches identify regions of importance for genetic
      susceptibility to hereditary esophageal squamous cell carcinoma.
AB  - Worldwide, the highest prevalence of esophageal cancer (EC) occurs in Northern
      China. High-density SNP arrays allow identification of identity-by-descent (IBD)
      segments in genomic DNAs representative of shared common ancestral regions. We
      utilized IBD approaches to map susceptibility loci associated with low-penetrance
      SNPs in high-risk Henan hereditary esophageal squamous cell carcinoma (ESCC)
      patients. Affymetrix GeneChip Human mapping SNP array IBD analysis was performed
      in 32 Henan family history-positive (FH+) ESCC patients, 18 Henan healthy
      unrelated individuals, and 45 Chinese individuals from a CHB HapMap dataset using
      PLink (scoring IBD segments individually) and Beagle (scoring of shared IBD
      segments among case/case vs. control/control pairs) software. Both analyses
      identified longer IBD segment lengths associated with FH+ ESCC compared to
      controls. However, there was no strong evidence for a genetic founder effect.
      Pairing IBD analysis with BEAGLE identified 8 critical IBD segments residing at
      2q32.1-q32.2, 3p22.3-p22.2, 4q21.1-q21.21, 7p22.2, 8q23.2-q23.3, 10q23.33-q24.1,
      14q24.3 and 16q11.2-q12.1, which were more significantly shared among case/case
      compared to control/control. The shared IBD segments in FH+ ESCC samples with no
      overlap with control/CHB Hapmap may encompass potential cancer susceptibility
      loci. Selected targeted genes, PLCE1, GPT2, SIAH1 and CYP2C-18, residing within
      the IBD segments at 10q23.33-q24.1 and 16q11.2-q12.1, had statistically
      significant differential expression in primary ESCC tissues and are likely
      involved in ESCC carcinogenesis. The importance of these IBD segments to the
      etiology and development of ESCC in high-risk areas requires further study with
      expanded sample sizes. This is the first report employing the pairing IBD
      approach for elucidation of the genetic basis of hereditary ESCC in Henan by
      applying high throughput SNP array analysis.

PMID- 24890310
TI  - Loco-regional control after neo-adjuvant chemotherapy and conservative treatment
      for locally advanced breast cancer patients.
AB  - Breast-conserving treatment (BCT) has been validated for breast cancer patients
      receiving adjuvant chemotherapy. Our objective was to evaluate the difference in
      loco-regional recurrence (LRR) rates between BCT and mastectomy in patients
      receiving radiation therapy after neo-adjuvant chemotherapy (NCT). A
      retrospective data base was used to identify all patients with breast cancer
      undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were
      excluded from this analysis. LRR was compared between those undergoing BCT and
      mastectomy. Individual variables associated with LRR were evaluated. Two hundred
      eighty-four patients were included, 111 (39%) underwent BCT and 173 (61%)
      mastectomy. Almost all patients (99%) in both groups received postoperative
      radiation. Pathologic complete response was seen in 37 patients, of which 28
      underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive
      lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer
      (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow-up
      of 6.3 years, the loco-regional control rate was 91% (95% CI: 86-94%). The 10
      year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9-16.7%]) and in the
      mastectomy group (10.7% [95% CI: 5.9-15.2%]; p = 0.8). Ten-year overall survival
      (OS) rates (63% [95% CI: 46-79%] in the BCT group; 60% [95% CI: 47-73%] in the
      mastectomy group, p = 0.8) were not statistically different between the two
      patient populations. Multivariate analysis showed that AJCC stage >= III (HR:
      2.6; 95% CI: 1.2-5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2-30.6, p = 0.03),
      and number of positive lymph nodes >=3 (HR: 2.5; 95% CI: 1.1-5.9; p = 0.03) were
      independent predictors of LRR. Ten-year OS was similar in the BCT and in the
      mastectomy group (p = 0.1). The rate of LRR was low and did not significantly
      differ between the BCT and the mastectomy group after NCT. Randomized trials
      assessing whether mastectomy can be safely omitted in selected breast cancer
      patients (nonstage III tumors or those which do not require adjuvant hormone
      suppression) which respond to NCT are required.

PMID- 24890311
TI  - Early outpatient referral to palliative care services improves end-of-life care.

PMID- 24890312
TI  - Substance use by same sex attracted young people: Prevalence, perceptions and
      homophobia.
AB  - INTRODUCTION AND AIMS: Research highlights that lesbian, gay, bisexual and
      transgender (LGBT) people use alcohol and drugs (AOD) more than heterosexual
      people; however, the incidence of AOD use by LGBT youth is less understood. The
      purpose of the current study was to ascertain AOD prevalence rates for LGBT youth
      compared with the Australian youth population; perceptions of AOD use within the
      LGBT community; and the impact of homophobia on AOD use. DESIGN AND METHODS: The
      study surveyed a cross-sectional sample of LGBT youth (13-24 years) (n = 161) who
      attended a LGBT festival in Brisbane, Australia, in 2012. The Alcohol Use
      Disorders Identification Test-Consumption, Fagerstrom Test for Nicotine
      Dependence and Drug Check Assessment Tool were utilised to examine patterns of
      AOD use, with items developed to explore perceptions of AOD use and homophobia.
      RESULTS: AOD use was common among the LGBT sample, with higher prevalence rates
      compared with the general Australian youth population (2010 National Drug
      Strategy Household Survey). AOD use by under 18-year-olds, and gender diverse
      youth was markedly higher. The majority misperceived AOD use to be the same in
      the LGBT and heterosexual communities. Those who believed homophobia impacted on
      AOD use were significantly more likely to use AOD. DISCUSSION AND CONCLUSIONS:
      The higher prevalence of AOD use strongly suggests the need for AOD agencies to
      better respond to LGBT youth by not only screening sexuality and gender identity
      but also exploring young people's perceptions of AOD use in the LGBT community
      and their experiences of homophobia in order to provide effective AOD clinical
      treatment.

PMID- 24890313
TI  - Enantioselective synthesis of benzazepinoindoles bearing trifluoromethylated
      quaternary stereocenters catalyzed by chiral spirocyclic phosphoric acids.
AB  - The first highly enantioselective iso-Pictet-Spengler reaction of C-2-linked o
      aminobenzylindoles with trifluoromethyl ketones was developed using chiral
      spirocyclic phosphoric acids as organocatalysts, which afforded optically active
      benzazepinoindoles bearing trifluoromethylated quaternary stereocenters. 

PMID- 24890314
TI  - Pharmacodynamic monitoring of immunosuppressive effects indicates reduced
      cyclosporine activity during telaprevir therapy.
AB  - Drug interactions with immunosuppressive drugs are a major problem associated
      with protease inhibitor-based antiviral triple therapy for hepatitis C virus
      (HCV) reinfection after liver transplantation. In this retrospective cohort
      study, we analyzed biomarkers of the immunosuppressive effects of cyclosporine A
      (CSA) by quantifying nuclear factor of activated T cells (NFAT)-regulated gene
      expression during telaprevir (TVR) therapy in 5 liver transplant patients.
      Furthermore, dose adjustments and blood concentrations of CSA as well as the
      clinical course were analyzed. We observed a clear impact of TVR not only on
      doses and blood concentrations but also on the immunosuppressive effects of CSA.
      Despite apparently adequate CSA trough concentrations, the CSA peak concentration
      decreased to 68% (range = 44%-90%). This was associated with a 1.9-fold (1.6- to
      4.1-fold) increase in the residual gene activity of NFAT-regulated genes, which
      indicated reduced immunosuppressive activity of CSA with TVR co-medication. The
      median dose of CSA was reduced to 25% (range = 16%-48%) and 31% (range = 22%-64%)
      after 1 and 2 weeks, respectively. The CSA drug clearance was reduced to 38.7%
      (range = 31.0%-49.4%). We report excellent antiviral efficacy. At the end of the
      observation period, all patients were HCV RNA-negative (1 patient at 18 weeks, 1
      patient at 12 weeks, and 3 patients at 4 weeks after the end of therapy). Safety
      was acceptable, with mild acute rejection and reactivation of cytomegalovirus
      being the most serious adverse events. One patient with histologically proven
      recurrent cholestatic hepatitis before therapy underwent retransplantation during
      the course of antiviral therapy. In conclusion, the immunomonitoring of NFAT
      regulated gene expression indicated reduced immunosuppressive activity of CSA
      during antiviral therapy with TVR in our cohort of liver transplant patients.
      Thus, the immunosuppressive effects of CSA may be overestimated if one is looking
      only at trough concentrations during co-medication with protease inhibitors or
      other strong cytochrome P450 3A inhibitors. Immunomonitoring of NFAT-regulated
      gene expression could, therefore, help to prevent overimmunosuppression or
      underimmunosuppression.

PMID- 24890315
TI  - Gender influence on schizophrenia-relevant abnormalities in a cuprizone
      demyelination model.
AB  - The aim of this study was to determine whether early demyelination can impact
      behavior in young adulthood. For this purpose, albino Wistar rats of either sex
      were exposed to cuprizone (CPZ) in two different intoxication protocols: one
      group was intoxicated before weaning (CPZ-BW), from postnatal day 7 (P7) to P21,
      through maternal milk, whereas the other group was intoxicated after weaning (CPZ
      AW), from P21 to P35. After treatment, rats were returned to a normal diet until
      P90 when behavioral studies were performed. Both treatments produced marked
      demyelination in the corpus callosum and retraction of cortical myelin fibers.
      The subsequent normal diet allowed for effective remyelination at P90.
      Interestingly, CPZ-AW correlated with significant behavioral and neurochemical
      changes in a gender-dependent manner. CPZ-AW treatment altered both the number of
      social activities and the latency to the first social interaction in males, while
      also highly compromising recognition-related activities. In addition, only P90
      males treated AW showed a hyperdopaminergic striatum, confirmed by an increase in
      tyrosine hydroxylase expression and in dopamine levels. Our results suggest that
      the timing of demyelination significantly influences the development of altered
      behavior, particularly in adult males.

PMID- 24890316
TI  - Tooth replacement without a dental lamina: the search for epithelial stem cells
      in Polypterus senegalus.
AB  - Most actinopterygians replace their teeth continuously throughout life. To
      address the question of where and how replacement teeth form in actinopterygians,
      it is advisable to investigate well-chosen representatives within the lineage.
      The African bichir, Polypterus senegalus, belongs to the earliest diverged group
      of the actinopterygian lineage with currently living representatives. Its well
      characterized dentition, together with its phylogenetic position, make this
      species an attractive model to answer following questions: (1) when and where
      does the replacement tooth form and how is it connected with the dental organ of
      the predecessor, and (2) is there any evidence for the presence of epithelial
      stem cells, hypothesized to play a role in replacement? Serial sections show that
      one tooth family can contain up to three members, which are all interconnected by
      dental epithelium. Replacement teeth develop without the presence of a
      successional dental lamina. We propose that this is the plesiomorphic condition
      for tooth replacement in actinopterygians. BrdU pulse-chase experiments reveal
      cells in the outer and middle dental epithelium, proliferating at the time of
      initiation of a new replacement tooth. It is tempting to assume that these cell
      layers provide a stem cell niche. The observed absence of label-retaining cells
      after long chase times (up to 8 weeks) is held against the light of divergent
      views on cell cycling properties of stem cells. At present, our data do not
      support, neither reject, the hypothesis on involvement of epithelial stem cells
      within the process of continuous tooth replacement.

PMID- 24890317
TI  - Mechanism of GABA involvement in post-traumatic trigeminal neuropathic pain:
      activation of neuronal circuitry composed of PKCgamma interneurons and pERK1/2
      expressing neurons.
AB  - BACKGROUND: GABA disinhibition within the spinal dorsal horn has been implicated
      in pain hypersensitivity on injury in different neuropathic models. However, GABA
      alteration has been explored in only one study on trigeminal neuropathic pain.
      METHODS: The present study investigated the implication of GABA in trigeminal
      dynamic mechanical allodynia (DMA) obtained after chronic constriction of the
      infraorbital nerve (CCI-IoN), and explored the cellular and molecular mechanisms
      by which GABA dysfunction induced DMA. RESULTS: Our data demonstrated a
      significant decrease in labelling in two GABA cell markers, glutamate acid
      decarboxylase (GAD67), and parvalbumin, in the medullary dorsal horn (MDH) of
      allodynic rats in comparison to sham rats. Increasing GABA by intracisternal
      injections of vigabatrin (VGB), a blocker of the catabolic enzyme GABA
      transaminase, alleviated pain behaviour and restored normal GABA cell marker
      expression in allodynic MDH. Interestingly, intracisternal VGB administration
      also significantly decreased PKCgamma staining, i.e., of its phosphorylated
      active form and the number of pERK1/2 positive cells within the MDH. These two
      markers were highly expressed in allodynic MDH. CONCLUSION: The circuitry
      composed of PKCgamma and pERK1/2 cells is silent under physiological conditions
      but is activated after CCI-IoN, therefore, switching touch stimuli to pain
      sensation. The decrease of GABA transmission constituted a key factor in the
      activation of this neuronal circuitry, which opens the gate for non-noxious
      stimuli to reach nociceptive projection neurons in lamina I.

PMID- 24890319
TI  - Restoration of adiponectin expression via the ERK pathway in TNFalpha-treated 3T3
      L1 adipocytes.
AB  - Adiponectin and tumor necrosis factor-alpha (TNF-alpha) exert opposite effects on
      obesity-associated inflammation and insulin signaling. The purpose of the present
      study was to investigate the effects of chronic TNF-alpha on adiponectin levels
      in 3T3-L1 adipocytes, as well as the potential reversal mechanisms.
      Differentiated 3T3-L1 adipocytes were exposed to TNF-alpha for three different
      incubation times and then to various wash-off periods with or without mitogen
      activated protein kinase (MAPK) inhibitors. TNF-alpha significantly reduced
      adiponectin gene expression in a dose- and time-dependent manner and activated c
      Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and
      p38 MAPK. A 16 h restoration period fully reversed the decrease in adiponectin
      levels following 16 h treatment with TNF-alpha; however, 16 h withdrawal of TNF
      alpha following 32 or 48 h treatment did not completely reverse the TNF-alpha
      induced decrease in adiponectin levels. In 3T3-L1 adipocytes, 32 or 48 h wash-off
      periods were required following 32 or 48 h TNF-alpha treatments, respectively.
      The pattern of ERK activation following TNF-alpha exposure and removal was
      similar to the pattern of adiponectin expression. Furthermore, ERK1/2 inhibition
      accelerated the recovery of adiponectin levels compared with the levels in the
      untreated control adipocytes. Therefore, the inhibitory effects of TNF-alpha on
      adiponectin levels in differentiated 3T3-L1 cells were fully reversed following a
      wash-out period equivalent to the TNF-alpha treatment time, potentially through
      the ERK 1/2 pathway. 

PMID- 24890318
TI  - Targeting the androgen receptor in prostate cancer.
AB  - INTRODUCTION: The androgen receptor (AR) is a ligand-activated transcription
      factor that is expressed in primary and metastatic prostate cancers. There are
      advances in endocrine therapy for prostate cancer that are based on improved
      understanding of AR function. AREAS COVERED: PubMed has been used to include most
      important publications on targeting the AR in prostate cancer. AR expression may
      be downregulated by agents used for chemoprevention of prostate cancer or, in
      models of advanced prostate cancer, by antisense oligonucleotides. New drugs that
      inhibit the steroidogenic enzyme CYP17A1 (abiraterone acetate) or diminish
      nuclear translocation of the AR (enzalutamide) have been shown to improve
      patients' survival in prostate cancer. However, it is clear that there is a
      development of resistance to these novel therapies. They may include increased
      expression of truncated, constitutively active AR or activation of the signaling
      pathway of signal transducers and activators of transcription. EXPERT OPINION:
      Although introduction of novel drugs have improved patients' survival, there is a
      need to investigate the mechanisms of resistance further. The role of truncated
      AR and compensatory activation of signaling pathways as well as the development
      of scientifically justified combination therapies seems to be issues of a high
      priority.

PMID- 24890320
TI  - Anti-plasticizing effect of amorphous indomethacin induced by specific
      intermolecular interactions with PVA copolymer.
AB  - The mechanism of how poly(vinyl alcohol-co-acrylic acid-co-methyl methacrylate)
      (PVA copolymer) stabilizes an amorphous drug was investigated. Solid dispersions
      of PVA copolymer, poly(vinyl pyrrolidone) (PVP), and poly(vinyl pyrrolidone-co
      vinyl acetate) (PVPVA) with indomethacin (IMC) were prepared. The glass
      transition temperature (Tg)-proportion profiles were evaluated by differential
      scanning calorimetry (DSC). General Tg profiles decreasing with the IMC ratio
      were observed for IMC-PVP and IMC-PVPVA samples. An interesting antiplasticizing
      effect of IMC on PVA copolymer was observed; Tg increased up to 20% IMC ratio.
      Further addition of IMC caused moderate reduction with positive deviation from
      theoretical values. Specific hydrophilic and hydrophobic interactions between IMC
      and PVA copolymer were revealed by infrared spectra. The indole amide of IMC
      played an important role in hydrogen bonding with PVA copolymer, but not with PVP
      and PVPVA. X-ray diffraction findings and the endotherm on DSC profiles suggested
      that PVA copolymer could form a semicrystalline structure and a possibility of
      correlation of the crystallographic nature with its low hygroscopicity was
      suggested. PVA copolymer was able to prevent crystallization of amorphous IMC
      through both low hygroscopicity and the formation of a specific intermolecular
      interaction compared with that with PVP and PVPVA.

PMID- 24890321
TI  - Prevention of diaper dermatitis in infants--a literature review.
AB  - Diaper dermatitis (DD) is one of the most common skin conditions in neonates and
      infants, with a peak between the ages of 9 and 12 months. Appropriate skin care
      practices that support skin barrier function and protect the buttocks skin from
      urine and feces are supposed to be effective in the prevention of DD. Despite
      many recommendations for parents and caregivers on proper diaper skin care, there
      is no up-to-date synthesis of the available evidence to develop recommendations
      for DD prevention practice. Therefore we performed a systematic literature review
      on the efficacy of nonmedical skin care practices on the diapered area of
      healthy, full-term infants ages 0 to 24 months. We identified 13 studies covering
      skin care practices such as cleansing, bathing, and application of topical
      products. DD prevalence and incidence and physiologic skin parameters were used
      as efficacy parameters. The results of this review indicate that cleansing of the
      diaper area using baby wipes or water and a washcloth have comparable effects on
      diapered skin. Bathing with a liquid baby cleanser twice weekly seems comparable
      with water alone. The application of ointments containing zinc oxide or
      petrolatum with or without vitamin A seems to have comparable effects on DD
      severity. There seems to be no information on whether single skin care practices
      such as cleansing, bathing, and application of topical preparations can prevent
      DD. High-quality randomized clinical trials are needed to show the effectiveness
      of skin care practices for controlling and preventing DD. 

PMID- 24890322
TI  - The jack of all trades is master of none: a pathogen's ability to infect a
      greater number of host genotypes comes at a cost of delayed reproduction.
AB  - A trade-off between a pathogen's ability to infect many hosts and its
      reproductive capacity on each host genotype is predicted to limit the evolution
      of an expanded host range, yet few empirical results provide evidence for the
      magnitude of such trade-offs. Here, we test the hypothesis for a trade-off
      between the number of host genotypes that a fungal pathogen can infect (host
      genotype range) and its reproductive capacity on susceptible plant hosts. We used
      strains of the oat crown rust fungus that carried widely varying numbers of
      virulence (avr) alleles known to determine host genotype range. We quantified
      total spore production and the expression of four pathogen life-history stages:
      infection efficiency, time until reproduction, pustule size, and spore production
      per pustule. In support of the trade-off hypothesis, we found that virulence
      level, the number of avr alleles per pathogen strain, was correlated with
      significant delays in the onset of reproduction and with smaller pustule sizes.
      Modeling from our results, we conclude that trade-offs have the capacity to
      constrain the evolution of host genotype range in local populations. In contrast,
      long-term trends in virulence level suggest that the continued deployment of
      resistant host lines over wide regions of the United States has generated
      selection for increased host genotype range. 

PMID- 24890324
TI  - Emerging pathogen in immunocompromised hosts: Exophiala dermatitidis mycosis in
      graft-versus-host disease.
AB  - Infection with the dematiaceous environmental fungus Exophiala, an emerging
      pathogen in immunocompromised individuals, poses a diagnostic and therapeutic
      challenge. Herein, we report the first Exophiala dermatitidis fungemia case, to
      our knowledge, in an allogeneic hematopoietic stem cell transplant patient with
      graft-versus-host disease, expanding the clinical setting where Exophiala species
      mycosis should be suspected.

PMID- 24890323
TI  - Understanding the effects of stress and alcohol cues on motivation for alcohol
      via behavioral economics.
AB  - BACKGROUND: Psychological stress and alcohol cues are common antecedents of both
      ongoing drinking and relapse. One candidate mechanism of risk from these factors
      is acute increases in craving, but experimental support for this hypothesis is
      mixed. Furthermore, the combination of stress and cues has been largely
      unstudied. The current study employed a behavioral economic approach to
      investigate the combined roles of psychosocial stress and alcohol cues on
      motivation for alcohol. METHODS: In a sample of 84 adult heavy drinkers, we
      examined the effects of an acute laboratory stress induction and an alcohol cue
      exposure on subjective craving and stress, arousal, and behavioral economic
      decision making. Primary dependent measures included an intertemporal cross
      commodity multiple-choice procedure (ICCMCP), incorporating both price and delay
      elements, an alcohol purchase task (APT), measuring alcohol demand, and a
      monetary delay discounting task, measuring intertemporal choice. RESULTS: The
      stress induction significantly increased stress, craving, and the incentive value
      of alcohol on the ICCMCP and APT. Stress-related increases in value on the ICCMCP
      were mediated by increased alcohol demand. Exposure to alcohol cues only
      significantly affected craving, APT breakpoint, and arousal. Delay discounting
      was not affected by either stress or cues. CONCLUSIONS: These results reveal
      unique behavioral economic dimensions of motivation for alcohol following acute
      stress and an alcohol cue exposure. More broadly, as the first application of
      this approach to understanding the role of stress in drug motivation, these
      findings support its utility and potential in future applications.

PMID- 24890325
TI  - Cereal, fruit and vegetable fibre intake and the risk of the metabolic syndrome:
      a prospective study in the Tehran Lipid and Glucose Study.
AB  - BACKGROUND: The present study aimed to determine whether total fibre or specific
      fibre food sources are associated with the incidence of the metabolic syndrome
      (MetS) after 3 years of follow-up in the Tehran Lipid and Glucose Study. METHODS:
      This population-based prospective study, conducted within the framework of the
      Tehran Lipid and Glucose Study, included 1582 adults, who were aged 19-84 years
      and free of MetS at baseline. Usual dietary fibre intake was assessed at baseline
      using a 168-item food frequency questionnaire. Anthropometrics, blood pressure,
      and fasting blood glucose and lipid profiles were measured at baseline and 3
      years later. The MetS was defined according to the definition of the revised
      Adult treatment Panel III. RESULTS: During the 3-year follow-up, there was 15.2%
      incidence of MetS. Among sources of dietary fibre, fruit fibre was significantly
      and inversely associated with the occurrence of MetS, after adjustment for
      confounding factors, with a 21% lower risk [odds ratio (OR) = 0.79, 95%
      confidence interval (CI) = 0.60-0.97] in the highest tertile of intake compared
      to the lowest tertile. Subjects in the highest tertile of cereal fibre intake had
      lower odds of MetS compared to those in the lowest tertile (OR = 0.73, 95% CI =
      0.52- 0.97) and this association disappeared after adjustment for confounders. No
      significant association was found between intakes of vegetables, legumes and nut
      fibre with the incidence of MetS. CONCLUSIONS: Among specific fibre food sources,
      fruit fibre had a protective effect against the risk of MetS.

PMID- 24890326
TI  - Hyaluronic acid in psoriasis.

PMID- 24890328
TI  - Simultaneous quantification of catecholamines in rat brain by high-performance
      liquid chromatography with on-line gold nanoparticle-catalyzed luminol
      chemiluminescence detection.
AB  - A new method based on high-performance liquid chromatography (HPLC) coupled with
      on-line gold nanoparticle-catalyzed luminol chemiluminescence (CL) detection was
      developed for the simultaneous quantitation of catecholamines in rat brain. In
      the present CL system, gold nanoparticles were produced by the on-line reaction
      of H2 O2 , NaHCO3 -Na2 CO3 (buffer solution of luminol) and HAuCl4.
      Norepinephrine (NE), epinephrine (EP) and dopamine (DA) could strongly enhance
      the CL signal of the on-line gold nanoparticle-catalyzed luminol system. The UV
      visible absorption spectra and transmission electron microscopy studies were
      carried out, and the CL enhancement mechanism was proposed. Catecholamines
      promoted the on-line formation of more gold nanoparticles, which better catalyzed
      the luminol-H2 O2 CL reaction. The good separation of NE, EP and DA was achieved
      with isocratic elution using a mixture of methanol and 0.2% aqueous phosphoric
      acid (5:95, v/v) within 8.5 min. Under the optimized conditions, the detection
      limits, defined as a signal-to-noise ratio of 3, were in the range of 1.32-1.90
      ng/mL, corresponding to 26.4-38.0 pg for 20 MUL sample injection. The recoveries
      of catecholamines added to rat brain sample were >94.6%, with the precisions
      <5.5%. The validated HPLC-CL method was successfully applied to determine NE and
      DA in rat brain without prior sample purification.

PMID- 24890327
TI  - Elevated serum CA19-9 level is a promising predictor for poor prognosis in
      patients with resectable pancreatic ductal adenocarcinoma: a pilot study.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive
      human cancers. Several studies have reported that the carbohydrate antigen 19-9
      (CA19-9) level is a useful marker for predicting the prognosis for PDAC after
      resection. However, the cutoff value of CA19-9 used to predict prognosis varied
      among these reports. The aims of this study were to evaluate whether the serum
      CA19-9 level is a significant predictor for survival and to determine the optimal
      cutoff value of CA19-9 for predicting prognosis. METHODS: A total of 120
      consecutive patients who underwent surgery for potentially resectable primary
      PDAC were retrospectively analyzed. The variables included the following: age,
      sex, the location of the tumor, the maximal tumor size, the histological
      differentiation, the margin status, the tumor stage, serum CA19-9 levels, and
      serum total bilirubin (TBil) levels. RESULTS: The overall 1-year survival rate
      was 62.5%. The receiver operating characteristic (ROC) curve indicated a
      significant result for the level of CA19-9 in predicting death within 1 year
      after surgery (Area under the curve (AUC), 0.612; 95% confidence interval (CI),
      0.505-0.720; P = 0.040). The optimal cutoff point was 338.45 U/mL (sensitivity,
      60.0%; specificity, 66.7%; accuracy, 64.2%). The strongest univariate predictor
      among the categorized CA19-9 values was CA19-9 greater than or equal to 338.45
      U/mL. In the multivariate Cox proportional hazards mode analysis, the serum CA19
      9 level, age and the histological differentiation were significant independent
      prognostic factors that were associated with the overall survival. CONCLUSIONS:
      The preoperative elevated CA19-9 level is a promising independent factor for
      predicting a poor prognosis in PDAC, and the optimal cutoff value is 338.45 U/mL.

PMID- 24890329
TI  - Bronchial inflammation in hypersensitivity pneumonitis after antigen-specific
      inhalation challenge.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to compare the inflammatory
      profile before and after specific inhalation challenge (SIC) in induced sputum
      from patients with hypersensitivity pneumonitis (HP) and to investigate whether
      different causal antigens define the resulting profile. METHODS: A prospective
      study was conducted in 27 patients with HP: 15 patients due to exposure to birds
      (BHP) and 12 due to exposure to fungi (FHP), confirmed by SIC. Induced sputum was
      obtained before and/or 24 h after SIC. Cell types were determined by differential
      cell count using optical microscopy. Interferon-gamma, interleukin (IL)-12p70, IL
      2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1beta, tumour necrosis factor (TNF)-alpha
      and TNF-beta levels were measured in the supernatants. RESULTS: Following SIC,
      higher sputum neutrophilia levels (P = 0.048) and an increase in IL-8 levels (P =
      0.017) were found in patients with FHP than in those with BHP. FHP patients also
      showed increased IL-1beta, IL12-p70 and IL5 levels (P = 0.011, P = 0.036 and P =
      0.018, respectively) after SIC. In BHP, a trend towards increases in sputum
      eosinophils and TH2 cytokines (IL4, IL5) was seen following SIC (P = 0.059, P =
      0.068 and P = 0.075 respectively). CONCLUSIONS: This study shows that bronchial
      inflammation is present in patients with HP evidenced by increases in sputum
      neutrophils and eosinophils following exposure to the offending antigen during
      SIC.

PMID- 24890330
TI  - Root exudation of phytosiderophores from soil-grown wheat.
AB  - For the first time, phytosiderophore (PS) release of wheat (Triticum aestivum cv
      Tamaro) grown on a calcareous soil was repeatedly and nondestructively sampled
      using rhizoboxes combined with a recently developed root exudate collecting tool.
      As in nutrient solution culture, we observed a distinct diurnal release rhythm;
      however, the measured PS efflux was c. 50 times lower than PS exudation from the
      same cultivar grown in zero iron (Fe)-hydroponic culture. Phytosiderophore
      rhizosphere soil solution concentrations and PS release of the Tamaro cultivar
      were soil-dependent, suggesting complex interactions of soil characteristics
      (salinity, trace metal availability) and the physiological status of the plant
      and the related regulation (amount and timing) of PS release. Our results
      demonstrate that carbon and energy investment into Fe acquisition under natural
      growth conditions is significantly smaller than previously derived from zero Fe
      hydroponic studies. Based on experimental data, we calculated that during the
      investigated period (21-47 d after germination), PS release initially exceeded Fe
      plant uptake 10-fold, but significantly declined after c. 5 wk after germination.
      Phytosiderophore exudation observed under natural growth conditions is a
      prerequisite for a more accurate and realistic assessment of Fe mobilization
      processes in the rhizosphere using both experimental and modeling approaches. 

PMID- 24890331
TI  - Advanced mass spectrometry-based multi-omics technologies for exploring the
      pathogenesis of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the primary hepatic malignancies and is
      the third most common cause of cancer related death worldwide. Although a wealth
      of knowledge has been gained concerning the initiation and progression of HCC
      over the last half century, efforts to improve our understanding of its
      pathogenesis at a molecular level are still greatly needed, to enable clinicians
      to enhance the standards of the current diagnosis and treatment of HCC. In the
      post-genome era, advanced mass spectrometry driven multi-omics technologies
      (e.g., profiling of DNA damage adducts, RNA modification profiling, proteomics,
      and metabolomics) stand at the interface between chemistry and biology, and have
      yielded valuable outcomes from the study of a diversity of complicated diseases.
      Particularly, these technologies are being broadly used to dissect various
      biological aspects of HCC with the purpose of biomarker discovery, interrogating
      pathogenesis as well as for therapeutic discovery. This proof of knowledge-based
      critical review aims at exploring the selected applications of those defined
      omics technologies in the HCC niche with an emphasis on translational
      applications driven by advanced mass spectrometry, toward the specific clinical
      use for HCC patients. This approach will enable the biomedical community, through
      both basic research and the clinical sciences, to enhance the applicability of
      mass spectrometry-based omics technologies in dissecting the pathogenesis of HCC
      and could lead to novel therapeutic discoveries for HCC.

PMID- 24890332
TI  - A prospective three-step intervention study to prevent medication errors in drug
      handling in paediatric care.
AB  - AIMS AND OBJECTIVES: To prevent medication errors in drug handling in a
      paediatric ward. BACKGROUND: One in five preventable adverse drug events in
      hospitalised children is caused by medication errors. Errors in drug prescription
      have been studied frequently, but data regarding drug handling, including drug
      preparation and administration, are scarce. DESIGN: A three-step intervention
      study including monitoring procedure was used to detect and prevent medication
      errors in drug handling. METHODS: After approval by the ethics committee,
      pharmacists monitored drug handling by nurses on an 18-bed paediatric ward in a
      university hospital prior to and following each intervention step. They also
      conducted a questionnaire survey aimed at identifying knowledge deficits. Each
      intervention step targeted different causes of errors. The handout mainly
      addressed knowledge deficits, the training course addressed errors caused by rule
      violations and slips, and the reference book addressed knowledge-, memory- and
      rule-based errors. RESULTS: The number of patients who were subjected to at least
      one medication error in drug handling decreased from 38/43 (88%) to 25/51 (49%)
      following the third intervention, and the overall frequency of errors decreased
      from 527 errors in 581 processes (91%) to 116/441 (26%). The issue of the handout
      reduced medication errors caused by knowledge deficits regarding, for instance,
      the correct 'volume of solvent for IV drugs' from 49-25%. CONCLUSION: Paediatric
      drug handling is prone to errors. A three-step intervention effectively decreased
      the high frequency of medication errors by addressing the diversity of their
      causes. RELEVANCE TO CLINICAL PRACTICE: Worldwide, nurses are in charge of drug
      handling, which constitutes an error-prone but often-neglected step in drug
      therapy. Detection and prevention of errors in daily routine is necessary for a
      safe and effective drug therapy. Our three-step intervention reduced errors and
      is suitable to be tested in other wards and settings.

PMID- 24890333
TI  - Assessing change in mouthguard thickness according to the thickness of the
      original mouthguard sheet.
AB  - The aim of this study was to examine changes in thickness and differences in rate
      of change of mouthguard thickness according to the thickness of the original
      sheet used to form the mouthguard. The material used in this study was Sports
      Mouthguard (3.0, 3.8, and 5.0 mm thicknesses, ethylene vinyl acetate sheet). The
      sheets were heated until they hung 15 mm from the baseline and were then vacuum
      formed. The thickness of the mouthguard was measured, and the rate of change of
      thickness was calculated. The differences in thickness and rate of change of
      thickness at the labial surface of the central incisor and buccal surface of the
      first molar according to the thickness of sheet were analyzed by one-way anova,
      and that of the occlusal surface of the first molar was analyzed by the Kruskal
      Wallis test. The results showed that the thickness of mouthguard increased as the
      thickness of sheet increased (P < 0.05 or P < 0.01). The thickness of the sheet
      did not affect the rate of change of thickness at the central incisor and
      occlusal surface of the first molar. Adequate thickness could be obtained using
      the original sheet with a thickness >3.8 mm at the buccal surface of the first
      molar and >3.0 mm at the occlusal surface of the first molar. At the central
      incisor, the necessary thickness of the original sheet was calculated as 5.6 mm.
      These results would be useful for selecting the appropriate mouthguard sheet
      material.

PMID- 24890334
TI  - Does bilingualism influence cognitive aging?
AB  - Recent evidence suggests a positive impact of bilingualism on cognition,
      including later onset of dementia. However, monolinguals and bilinguals might
      have different baseline cognitive ability. We present the first study examining
      the effect of bilingualism on later-life cognition controlling for childhood
      intelligence. We studied 853 participants, first tested in 1947 (age = 11 years),
      and retested in 2008-2010. Bilinguals performed significantly better than
      predicted from their baseline cognitive abilities, with strongest effects on
      general intelligence and reading. Our results suggest a positive effect of
      bilingualism on later-life cognition, including in those who acquired their
      second language in adulthood.

PMID- 24890335
TI  - Two C3 -symmetric Dy3III complexes with triple di-MU-methoxo-MU-phenoxo bridges,
      magnetic ground state, and single-molecule magnetic behavior.
AB  - Two series of isostructural C(3)-symmetric Ln(3) complexes Ln(3)?[BPh(4)] and
      Ln(3)?0.33[Ln(NO(3))(6)] (in which Ln(III) =Gd and Dy) have been prepared from an
      amino-bis(phenol) ligand. X-ray studies reveal that Ln(III) ions are connected by
      one MU(2)-phenoxo and two MU(3)-methoxo bridges, thus leading to a hexagonal
      bipyramidal Ln(3)O(5) bridging core in which Ln(III) ions exhibit a biaugmented
      trigonal-prismatic geometry. Magnetic susceptibility studies and ab initio
      complete active space self-consistent field (CASSCF) calculations indicate that
      the magnetic coupling between the Dy(III) ions, which possess a high axial
      anisotropy in the ground state, is very weakly antiferromagnetic and mainly
      dipolar in nature. To reduce the electronic repulsion from the coordinating
      oxygen atom with the shortest Dy-O distance, the local magnetic moments are
      oriented almost perpendicular to the Dy(3) plane, thus leading to a paramagnetic
      ground state. CASSCF plus restricted active space state interaction (RASSI)
      calculations also show that the ground and first excited state of the Dy(III)
      ions are separated by approximately 150 and 177 cm(-1), for Dy(3)?[BPh(4)] and
      Dy(3)?0.33[Dy(NO(3))(6)], respectively. As expected for these large energy gaps,
      Dy(3)?[BPh(4)] and Dy(3)?0.33[Dy(NO(3)(6)] exhibit, under zero direct-current
      (dc) field, thermally activated slow relaxation of the magnetization, which
      overlap with a quantum tunneling relaxation process. Under an applied Hdc field
      of 1000 Oe, Dy(3)?[BPh(4)] exhibits two thermally activated processes with U(eff)
      values of 34.7 and 19.5 cm(-1), whereas Dy(3)?0.33[Dy(NO(3))(6)] shows only one
      activated process with Ueff =19.5 cm(-1).

PMID- 24890336
TI  - Tobacco and the pediatric chronic kidney disease population.
AB  - Tobacco use and exposure are preventable causes of morbidity and mortality.
      Whereas the impact of this public health issue is well described in adults with
      kidney disease, its role in the pediatric chronic kidney disease (CKD) population
      is largely unknown. This review discusses the prevalence of tobacco use and
      exposure in children with CKD, updates the reader on how tobacco affects the
      kidney, and presents intervention strategies relevant to this patient population.

PMID- 24890337
TI  - Albuminuria correlates with hemolysis and NAG and KIM-1 in patients with sickle
      cell anemia.
AB  - BACKGROUND: Although hyperfiltration and albuminuria are common pathological
      conditions, kidney injury (KI) biomarkers have been seldom studied in individuals
      with sickle cell anemia (SCA). METHODS: We undertook a cross-sectional assessment
      of urine KI biomarkers in children and adults with SCA with and without
      albuminuria and a normal estimated glomerular filtration rate (eGFR). Albumin, KI
      molecule 1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), endothelin-1 and
      transforming growth factor-beta1 (TGF-beta1) were measured. Assays were
      normalized by urine creatinine. Urine intracellular hemosiderin and serum lactate
      dehydrogenase (LDH) were assessed as markers of hemolysis. Albuminuria was
      associated to the biomarkers by Pearson and Spearman correlation coefficients.
      Differences between the albuminuria (yes, no) groups were assessed by the t test.
      RESULTS: Nineteen patients with albuminuria (mean urine albumin/creatinine 527.14
      +/- 1070 mg/g, range 38.3--190 mg/g) and 19 patients without albuminuria (mean
      urine albumin/creatinine 15.93 +/- 5.17 mg/g, range 7.9-28.4 mg/g) were studied.
      The age range for the whole group was 11-48 years, and 47 % were males. Patients
      with albuminuria were older, had lower hematocrit, were more likely to test
      positive for urine hemosiderin and had a higher KIM-1 (P = 0.0035) and NAG/
      creatinine ratios (P = 0.0062). Urine hemosiderin strongly correlated to a higher
      LDH level (P < 0.001). CONCLUSIONS: Despite a normal or increased eGFR, KI
      biomarkers were detected in the urine of individuals with SCA. NAG, KIM-1 and
      urine hemosiderin correlated with the presence of albuminuria.

PMID- 24890340
TI  - Association between participation in a brief diabetes education programme and
      glycaemic control in adults with newly diagnosed diabetes.
AB  - AIMS: To determine the association between participation in a brief introductory
      didactic diabetes education programme and change in HbA1c among individuals with
      newly diagnosed diabetes. METHODS: We identified a population-based cohort of
      adults newly diagnosed with diabetes between October 2005 and June 2008 in
      Calgary, Canada, and conducted a retrospective cohort study by linking
      administrative and laboratory data with programme attendance data. We matched
      individuals who attended the programme within the first 6 months after diagnosis
      with those who did not attend, based on their propensity scores. We measured the
      change in HbA1c between time of diagnosis and 6-18 months later to determine the
      association between programme participation and change in HbA1c . RESULTS: HbA1c
      was measured at baseline and follow-up for 7793 individuals, including 803
      programme participants. After propensity score matching, programme participation
      was associated with a significantly greater adjusted mean reduction in HbA1c
      between baseline and follow-up of 3.3 mmol/mol (95% CI 2.2-4.3) or 0.30% (95% CI
      0.20-0.39). There was a significant interaction between baseline HbA1c and
      programme participation-the difference in adjusted mean reduction in HbA1c
      associated with programme participation ranged from 2.7 mmol/mol (0.25%) at
      baseline HbA1c of 53 mmol/mol (7%) to 6.2 mmol/mol (0.56%) at baseline HbA1c of
      97 mmol/mol (11%). CONCLUSION: Despite its brevity, participation in a diabetes
      education programme was associated with an additional reduction in HbA1c in newly
      diagnosed people that was comparable with that reported in trials of programmes
      targeted at those with prevalent diabetes.

PMID- 24890339
TI  - Heightened graft failure risk during emerging adulthood and transition to adult
      care.
AB  - Emerging adulthood, defined as the interval between 18 and 25 years of age, is a
      socially-defined developmental stage. Although people in this age group appear
      physically mature, brain maturation is not complete until the end of this period.
      Perhaps due to this immaturity and a resulting inferior ability to manage chronic
      illness emerging adults with a variety of chronic health conditions are at a high
      risk for adverse outcomes. In this review I will summarize evidence that emerging
      adulthood constitutes a high-risk period for kidney transplant recipients, and
      consider the possible reasons for the spike in graft failure risk during this age
      interval-including age-related adherence behaviour and the changes in care
      organization, processes and structures associated with transfer from pediatric to
      adult-oriented care. I will also discuss evidence showing transfer from pediatric
      to adult-oriented care contributes to this elevated risk, and highlight the
      limitations and challenges of studies examining this question. Finally, I will
      direct readers to resources providing guidance on the best practices for care of
      patients transitioning to adult care.

PMID- 24890342
TI  - Development block of golden hamster ICSI embryos is associated with decreased
      expression of HDAC1, HSPA1A and MYC.
AB  - We have investigated the mechanism for embryo development block in vitro and to
      improve the development rate of golden hamster embryos in vitro. Intracytoplasmic
      sperm injection (ICSI) technique was used to produce golden hamster ICSI embryos.
      The changes in the histone acetylation and the expression of histone deacetylase
      and related genes were analyzed by immunocytochemical staining and real-time PCR
      both in golden hamster in vivo embryos and in ICSI embryos. Aged oocytes
      significantly increased the oocyte spontaneous activation rate. In vitro cultured
      ICSI embryos suffered from severe development block in M199TE medium. Expression
      of histone deacetylase 1 (HDAC1) was significantly decreased in the nuclei of the
      arrested ICSI 2-cell embryos, and its nuclear and cytoplasmic expression pattern
      was also markedly altered. The acetylation level of H4K5, however, was not
      significantly changed between golden hamster in vivo embryos and ICSI embryos.
      HSPA1A and MYC, the marker genes for zygotic genome activation (ZGA), were
      transcriptionally decreased in arrested ICSI 2-cell embryos. Transcription of
      HDAC1 was also downregulated in these embryos, whereas the mRNA expression of the
      proapoptotic gene, BAX, was not changed. These results indicate that the golden
      hamster ICSI embryo development block during ZGA is associated with decreased
      nuclear expression and altered expression of HDAC1. HSPA1A, MYC, and HDAC1 mRNA
      levels, which decrease, resulting in ZGA failure. 

PMID- 24890341
TI  - Nalfurafine suppresses pruritogen- and touch-evoked scratching behavior in models
      of acute and chronic itch in mice.
AB  - The kappa-opioid agonist, nalfurafine, has been approved in Japan for treatment
      of itch in patients with chronic kidney disease. We presently investigated if
      systemic administration of nalfurafine inhibited ongoing or touch-evoked
      scratching behavior (alloknesis) following acute intradermal injection of
      histamine or the non-histaminergic itch mediator, chloroquine, in mice. We also
      investigated if nalfurafine suppressed spontaneous or touch-evoked scratching in
      an experimental model of chronic dry skin itch. Nalfurafine reduced scratching
      evoked by histamine and chloroquine. Following acute histamine, but not
      chloroquine, low-threshold mechanical stimuli reliably elicited directed hindlimb
      scratching behavior, which was significantly attenuated by nalfurafine. In mice
      with experimental dry skin, nalfurafine abolished spontaneous scratching but had
      no effect on alloknesis. Nalfurafine thus appears to be a promising treatment for
      acute itch as well as ongoing itch of dry skin. 

PMID- 24890343
TI  - Highly conductive, flexible, and compressible all-graphene passive electronic
      skin for sensing human touch.
AB  - A facile and passive multiply flexible thin-film sensor is demonstrated based on
      thermoelectric effects in graphene. The sensor is highly conductive, free
      standing, flexible, and elastic. It senses heat and cold, and measures
      heated/cooled areas; it also discerns human touch from other pressures, locates
      human touch, and measures pressure levels. All of these sensing abilities are
      demonstrated without any internal/external power supply. 

PMID- 24890338
TI  - Defining nephrotic syndrome from an integrative genomics perspective.
AB  - Nephrotic syndrome (NS) is a clinical condition with a high degree of morbidity
      and mortality, caused by failure of the glomerular filtration barrier, resulting
      in massive proteinuria. Our current diagnostic, prognostic and therapeutic
      decisions in NS are largely based upon clinical or histological patterns such as
      "focal segmental glomerulosclerosis" or "steroid sensitive". Yet these
      descriptive classifications lack the precision to explain the physiologic origins
      and clinical heterogeneity observed in this syndrome. A more precise definition
      of NS is required to identify mechanisms of disease and capture various clinical
      trajectories. An integrative genomics approach to NS applies bioinformatics and
      computational methods to comprehensive experimental, molecular and clinical data
      for holistic disease definition. A unique aspect is analysis of data together to
      discover NS-associated molecules, pathways, and networks. Integrating
      multidimensional datasets from the outset highlights how molecular lesions impact
      the entire individual. Data sets integrated range from genetic variation to gene
      expression, to histologic changes, to progression of chronic kidney disease
      (CKD). This review will introduce the tenets of integrative genomics and suggest
      how it can increase our understanding of NS from molecular and pathophysiological
      perspectives. A diverse group of genome-scale experiments are presented that have
      sought to define molecular signatures of NS. Finally, the Nephrotic Syndrome
      Study Network (NEPTUNE) will be introduced as an international, prospective
      cohort study of patients with NS that utilizes an integrated systems genomics
      approach from the outset. A major NEPTUNE goal is to achieve comprehensive
      disease definition from a genomics perspective and identify shared molecular
      drivers of disease. 

PMID- 24890344
TI  - Hepatic lipogenesis and a marker of hepatic lipid oxidation, predict postprandial
      responses of triglyceride-rich lipoproteins.
AB  - OBJECTIVE: Postprandial hypertriglyceridemia is an important risk factor for
      cardiovascular disease. The mechanisms are still unclear. Here it was tested if
      hepatic de novo lipogenesis (DNL) and lipid oxidation influence the postprandial
      responses of triglyceride-rich lipoproteins (TRL) in humans. METHODS: The
      contribution of hepatic DNL to hepatic TRL production was analyzed in 67 men and
      women with a moderate range of BMI after a fat-rich meal. Also, lipase
      activities, liver fat, and 3-OH-butyrate were quantitated as an indicator of beta
      oxidation. Lipoproteins and metabolic markers were measured in fasting and
      postprandial blood samples. RESULTS: Postprandial DNL correlates with
      postprandial TG and apolipoprotein (apo) C-III responses in plasma and with TG,
      apoB48 and apoB100 responses in TRLs and their larger remnant particles. Fasting
      and 8-h postprandial DNL was inversely related to 3-OH-butyrate but not to liver
      fat content. Fasting apoC-III and 3-OH-butyrate, but not liver fat, independently
      predicted fasting DNL. CONCLUSIONS: The fasting and 8-h postprandial rate of DNL
      was inversely associated with the hepatic lipid oxidation in humans. DNL
      contributes significantly to the TG content in TRLs but not to the amount of
      liver fat, suggesting that an imbalance between DNL and fat oxidation contributes
      to postprandial atherogenic dyslipidemia.

PMID- 24890345
TI  - A review of safety, quality management, and practice guidelines for high-dose
      rate brachytherapy: executive summary.
AB  - This white paper was commissioned by the American Society for Radiation Oncology
      (ASTRO) Board of Directors to evaluate the status of safety and practice guidance
      for high-dose-rate (HDR) brachytherapy. Given the maturity of HDR brachytherapy
      technology, this white paper considers, from a safety point of view, the adequacy
      of general physics and quality assurance guidance, as well as clinical guidance
      documents available for the most common treatment sites. The rate of medical
      events in HDR brachytherapy procedures in the United States in 2009 and 2010 was
      0.02%, corresponding to 5-sigma performance. The events were not due to lack of
      guidance documents but failures to follow those recommendations or human failures
      in the performance of tasks. The white paper summarized by this Executive Summary
      reviews current guidance documents and offers recommendations regarding their
      application to delivery of HDR brachytherapy. It also suggests topics where
      additional research and guidance is needed. 

PMID- 24890346
TI  - Relating physician's workload with errors during radiation therapy planning.
AB  - PURPOSE: To relate subjective workload (WL) levels to errors for routine clinical
      tasks. METHODS AND MATERIALS: Nine physicians (4 faculty and 5 residents) each
      performed 3 radiation therapy planning cases. The WL levels were subjectively
      assessed using National Aeronautics and Space Administration Task Load Index
      (NASA-TLX). Individual performance was assessed objectively based on the severity
      grade of errors. The relationship between the WL and performance was assessed via
      ordinal logistic regression. RESULTS: There was an increased rate of severity
      grade of errors with increasing WL (P value = .02). As the majority of the higher
      NASA-TLX scores, and the majority of the performance errors were in the
      residents, our findings are likely most pertinent to radiation oncology centers
      with training programs. CONCLUSIONS: WL levels may be an important factor
      contributing to errors during radiation therapy planning tasks.

PMID- 24890348
TI  - Upper abdominal normal organ contouring guidelines and atlas: a Radiation Therapy
      Oncology Group consensus.
AB  - PURPOSE: To standardize upper abdominal normal organ contouring guidelines for
      Radiation Therapy Oncology Group (RTOG) trials. METHODS AND MATERIALS: Twelve
      expert radiation oncologists contoured the liver, esophagus, gastroesophageal
      junction (GEJ), stomach, duodenum, and common bile duct (CBD), and reviewed and
      edited 33 additional normal organ and blood vessel contours on an anonymized
      patient computed tomography (CT) dataset. Contours were overlaid and compared for
      agreement using MATLAB (MathWorks, Natick, MA). S95 contours, defined as the
      binomial distribution to generate 95% group consensus contours, and normal organ
      contouring definitions were generated and reviewed by the panel. RESULTS: There
      was excellent consistency and agreement of the liver, duodenal, and stomach
      contours, with substantial consistency for the esophagus contour, and moderate
      consistency for the GEJ and CBD contours using a Kappa statistic. Consensus
      definitions, detailed normal organ contouring recommendations and high-resolution
      images were developed. CONCLUSIONS: Consensus contouring guidelines and a CT
      image atlas should improve contouring uniformity in radiation oncology clinical
      planning and RTOG trials.

PMID- 24890347
TI  - RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized
      (1-3) spine metastases: phase 2 results.
AB  - PURPOSE: The phase 2 component of Radiation Therapy Oncology Group (RTOG) 0631
      assessed the feasibility and safety of spine radiosurgery (SRS) for localized
      spine metastases in a cooperative group setting. METHODS AND MATERIALS: Patients
      with 1-3 spine metastasis with a Numerical Rating Pain Scale (NRPS) score >=5
      received 16 Gy single fraction SRS. The primary endpoint was SRS feasibility:
      image guidance radiation therapy (IGRT) targeting accuracy <=2 mm, target volume
      coverage >90% of prescription dose, maintaining spinal cord dose constraints (10
      Gy to <=10% of the cord volume from 5-6 mm above to 5-6 mm below the target or
      absolute spinal cord volume <0.35 cc) and other normal tissue dose constraints. A
      feasibility success rate <70% was considered unacceptable for continuation of the
      phase 3 component. Based on the 1-sample exact binomial test with alpha = 0.10 (1
      sided), 41 patients were required. Acute toxicity was assessed using the National
      Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0.
      RESULTS: Sixty-five institutions were credentialed with spine phantom dosimetry
      and IGRT compliance. Forty-six patients were accrued, and 44 were eligible. There
      were 4 cervical, 21 thoracic, and 19 lumbar sites. Median NRPS was 7 at
      presentation. Final pretreatment rapid review was approved in 100%. Accuracy of
      image guided SRS targeting was in compliance with the protocol in 95%. The target
      coverage and spinal cord dose constraint were in accordance with the protocol
      requirements in 100% and 97%. Overall compliance for other normal tissue
      constraints was per protocol in 74%. There were no cases of grade 4-5 acute
      treatment-related toxicity. CONCLUSIONS: The phase 2 results demonstrate the
      feasibility and accurate use of SRS to treat spinal metastases, with rigorous
      quality control, in a cooperative group setting. The planned RTOG 0631 phase 3
      component will proceed to compare pain relief and quality of life between SRS and
      external beam radiation therapy.

PMID- 24890349
TI  - Radiation dose escalation using intensity modulated radiation therapy for gross
      unresected node-positive endometrial cancer.
AB  - PURPOSE: To determine rates of nodal control and survival in patients with
      endometrial cancer treated with intensity modulated radiation therapy (IMRT) with
      dose escalation to unresected nodal disease. METHODS AND MATERIALS: Between
      November 2005 and April 2011, 22 endometrial-cancer patients received IMRT with
      dose escalation to gross nodal disease with curative intent. Twelve were treated
      for recurrent disease (RD) and 10 in the primary setting, of whom 5 had a
      hysterectomy. The boost area included pelvic nodes in 9 patients (41%),
      paraaortic nodes (PAN) in 6 (27%) and both pelvic and PAN in 7 (32%). The median
      gross nodal dose was 63 Gy (range, 55-65). Rates of local control, disease-free
      survival (DFS) and overall survival (OS) were determined using the Kaplan-Meier
      method. RESULTS: Median follow-up time was 37.6 months (range, 10-88). Median
      nodal size was 2.25 cm (range, 1-6.9). The median time to first relapse after
      IMRT was 12 months (range, 6-49). Relapses occurred in 5/12 RD (42%), 1/5
      hysterectomy (20%), and 5/5 inoperable cases. Nodal relapses occurred in-field in
      3/12 RD and 1/5 hysterectomy patients. At 3 years, nodal control was 86%, DFS was
      58% and OS was 68%. Three patients experienced grade 3 late hematologic toxicity
      (anemia). No late grade >=3 gastrointestinal or genitourinary toxicity occurred.
      CONCLUSIONS: In endometrial cancer, the use of IMRT for dose escalation to gross
      nodal disease is feasible with acceptable rates of toxicity. Patients with nodal
      recurrence or unresectable nodal disease after a hysterectomy may benefit from
      radiation dose escalation.

PMID- 24890350
TI  - Combining prostate-specific antigen nadir and time to nadir allows for early
      identification of patients at highest risk for development of metastasis and
      death following salvage radiation therapy.
AB  - PURPOSE: Little is known regarding the prognostic capability of prostate-specific
      antigen (PSA) nadir (nPSA) and time to nPSA (TnPSA) following salvage radiation
      therapy (SRT) for biochemical failure (BF) postradical prostatectomy (RP). We
      sought to assess their prognostic significance in this setting. METHODS AND
      MATERIALS: A total of 448 patients who received SRT without androgen deprivation
      therapy at a single academic institution were included in this retrospective
      analysis. Univariate analysis and multivariate Cox proportional hazards models
      were used to assess BF, distant metastasis (DM), prostate cancer-specific death
      (PCSD), and overall survival (OS). A prognostic nomogram incorporating nPSA and
      TnPSA was developed and validated in randomly allocated training and validation
      cohorts. RESULTS: Median follow-up post-SRT was 64 months. Median nPSA and TnPSA
      were undetectable and 6.7 months, respectively. On univariate analysis, a
      detectable nPSA (P < .01) and TnPSA <6 months (P < .01) were predictive of all
      outcomes. In a training cohort, a 14-point nomogram incorporating detectable
      nPSA, TnPSA, Gleason score, pre-radiation therapy PSA, and seminal vesicle
      invasion predicted BF (hazard ratio[HR], 1.4; P < .0001), DM (HR, 1.3; P <
      .0001), PCSD (HR, 1.3; P < .0001), and decreased OS (HR, 1.2; P < .0001). Adding
      nPSA and TnPSA improved the prognostic value of the nomogram compared to using
      clinical predictors only. The nomogram was evaluated in a validation cohort where
      it was predictive of BF (c-index = 0.77), DM (0.73), and PCSD (0.69).
      CONCLUSIONS: Patients with a detectable nPSA also having a TnPSA <6 months post
      SRT are at high-risk for DM, PCSD, and decreased OS. These patients are unlikely
      to have clinically localized disease and should be considered for initiation of
      systemic therapies.

PMID- 24890351
TI  - Image guided radiation therapy for bladder cancer: assessment of bladder motion
      using implanted fiducial markers.
AB  - PURPOSE: To determine bladder wall position variability during external beam
      radiation therapy (EBRT) for bladder cancer with intravesical fiducial markers
      using 2-dimensional (2D) and volumetric (3D) imaging registration. METHODS AND
      MATERIALS: Twenty T2-4aN0-1 bladder cancer patients underwent definitive EBRT
      with concurrent chemotherapy between May 2001 and January 2012, and had
      intravesical fiducial marker placement before simulation. Computed tomographic
      (CT)-based treatment planning was used for an initial phase to deliver 45 Gy (1.8
      Gy/fraction) to the bladder and pelvic lymphatics followed by a boost to the
      involved bladder wall for an additional 21.6 Gy (1.8 Gy/fraction). Orthogonal
      kilovoltage radiograph images (34-37 images/patient) were obtained daily,
      registered with digitally reconstructed radiographs from the planning scan.
      Translational corrections were made daily. A kilovoltage cone-beam CT (kVCBCT)
      was acquired weekly and its registration with the planning scan was compared with
      that day's 2D registration results. RESULTS: Of 739 treatments, 6% resulted in
      >=15 mm displacement in 1 or more directions and 26% resulted in >=10 mm
      displacement in 1 or more directions. Based on 2D registrations, the average
      millimeter difference between bony registration and fiducial marker registration
      (BR-FMR) in the right-left (RL) (R+), anterior-posterior (AP) (A+), and superior
      inferior (SI) (I+) directions were: 0.5 +/- 1.0 (range, -2.0 to +3.8), 1.7 +/-
      4.4 (range, -8.1 to +13.5) and -3.7 +/- 5.8 (range, -16.8 to +8.3), respectively.
      For kVCBCT registrations, the average mm difference in the RL, AP, and SI
      directions were 0.3 +/- 2.1 (range, -2.4 to +5.1), 3.1 +/- 5.9 (range, -2.9 to
      +13.3) and -4.8 +/- 8.0 (range, -16.4 to +9.5), respectively. CONCLUSIONS: Using
      intravesical fiducial markers, the largest difference in bladder motion based BR
      FMR differences was in the superior-inferior direction. Because fiducial markers
      are target surrogates, setup using bony anatomy alone can lead to target
      displacements up to 13.5 mm anteriorly and 16.8 mm superiorly. This confirms a
      1.5-1.7 cm minimum in planning target margins. These findings suggest a
      significant advantage in using intravesical fiducial markers to determine daily
      translational corrections.

PMID- 24890352
TI  - Therapeutic radiation dose delivered to the low axilla during whole breast
      radiation therapy in the prone position: implications for targeting the
      undissected axilla.
AB  - PURPOSE: One interpretation of the American College of Surgeons Oncology Group
      Z0011 trial is that whole breast radiation therapy, known to treat a portion of
      the low axilla when delivered in the supine position, can treat residual
      microscopic disease in patients with involved axillary nodes that were not
      removed by axillary dissection. The purpose of this study was to quantify
      radiation dose delivered to the axilla for patients treated in the prone
      position. METHODS AND MATERIALS: We analyzed treatment plans from 40 consecutive
      patients who received radiation targeting the intact breast with tangent fields
      in the prone position. Axillary levels were contoured using Radiation Therapy
      Oncology Group (RTOG) definitions and radiation dose- volume calculations were
      made for axillary levels, heart, and lungs. We generated revised plans for 10
      patients by modifying the tangent beams to increase axillary dose and compared
      original with modified plans. RESULTS: The median proportion of the axilla
      covered by 90% of the prescription dose was 13% of level I (range, 0%-61%), 0% of
      level II (range, 0%-6%), and 0% of level III (range, 0%-0%). More of the level I
      axilla was covered in obese compared with nonobese patients (P = .013). Level I
      coverage did not differ significantly by laterality (P = .740) or tumor location
      (P = .527). Modification of the treatment plans significantly increased level I
      coverage (P = .005) with all modified plans delivering 90% of the prescription
      dose to at least 96% of the level I axilla. The modified plans had increased lung
      (P = .005) and heart (P = .028) dose, which were within acceptable RTOG normal
      tissue constraints. CONCLUSIONS: Most patients treated with standard whole breast
      tangential radiation in the prone position receive subtherapeutic dose to the
      level I and II axilla. Patients treated in the prone position who require
      therapeutic radiation dose to the low axilla need treatment field modification;
      this is feasible for many patients using tangent fields.

PMID- 24890353
TI  - Breathing adapted radiation therapy in comparison with prone position to reduce
      the doses to the heart, left anterior descending coronary artery, and
      contralateral breast in whole breast radiation therapy.
AB  - PURPOSE: To compare 3 different treatment positions in whole breast radiation
      therapy in terms of target volume coverage and doses to the organs at risk (OAR).
      METHODS AND MATERIALS: Thirty-four breast cancer (BC) patients (17 right-sided
      and 17 left-sided) were included in this dosimetric planning study. They all
      underwent a computed tomography (CT) scan in standard supine position in free
      breathing (FB), supine position with gating in deep inspiratory breath hold
      (DIBH)(G), and prone position (P). Three-dimensional treatment plans were made
      for all 3 CTs. Target coverage and OAR sparing were evaluated. RESULTS: Breast
      volumes varied between 209 and 2814 cm(3). The target coverage, expressed as the
      mean volume of the breast receiving at least 95% of the prescription dose, was
      similar for the 3 treatment positions. The mean lung dose and the volume of the
      lungs receiving >20 Gy were significantly lower in P (1.7 Gy; 2.3%) compared with
      G (3.4 Gy; 5.6%; P < .0001) and FB (4 Gy; 7.3%; P < .0001). The volume of the
      contralateral breast receiving >5 Gy was significantly lower in G (P = .001) or
      FB (P = .004) versus prone. The supine position with gating in DIBH significantly
      reduced the volume of the heart receiving >30 Gy (V30(heart)), the mean heart
      (D(heart)), and mean left anterior descending coronary artery (LAD) dose (D(LAD))
      for left-sided BC patients (V30(heart) 0.9%, D(heart) 1.6 Gy, DLAD 22.4 Gy) with
      respect to FB (V30(heart) 4.3%, D(heart) 3.5 Gy, DLAD 30.9 Gy)(V30(heart) and
      mean D(heart): P <= .0001; mean D(LAD): P = .008) and P (V30(heart) 7.9%,
      D(heart) 5.4 Gy, D(LAD) 36.4 Gy)(V30(heart) and mean D(heart): P = .0004; mean
      D(LAD): P = .01). CONCLUSIONS: The coverage of the planning target volume breast
      was equal for the 3 treatment positions. The lowest doses to the lungs were
      achieved in prone. The heart, LAD, and contralateral breast were best spared in
      the supine position with gating in DIBH.

PMID- 24890354
TI  - Taste and smell disturbances after brain irradiation: a dose-volume histogram
      analysis of a prospective observational study.
AB  - PURPOSE: Radiation-induced taste and smell disturbances are prevalent in patients
      receiving brain radiation therapy, although the mechanisms underlying these
      toxicities are poorly understood. We report the results of a single institution
      prospective clinical trial aimed at correlating self-reported taste and smell
      disturbances with radiation dose delivered to defined areas within the brain and
      nasopharynx. METHODS AND MATERIALS: Twenty-two patients with gliomas were
      enrolled on a prospective observational trial in which patients underwent a
      validated questionnaire assessing taste and smell disturbances at baseline and at
      3 and 6 weeks after commencement of brain radiation therapy. Fourteen patients
      with glioblastoma, 3 patients with grade 3 gliomas, and 5 patients with low grade
      gliomas participated. Median dose to tumor volume was 60 Gy (range, 45-60 Gy).
      Dose-volume histogram (DVH) analysis was performed for specific regions of
      interest that were considered potential targets of radiation damage, including
      the thalamus, temporal lobes, nasopharynx, olfactory groove, frontal pole, and
      periventricular stem cell niche. The %v10 (percent of region of interest
      receiving 10 Gy), %v40, and %v60 were calculated for each structure. Data from
      questionnaires and DVH were analyzed using stepwise regression. RESULTS: Twenty
      of 22 patients submitted evaluable questionnaires that encompassed at least the
      entire radiation therapy course. Ten of 20 patients reported experiencing some
      degree of smell disturbance during radiation therapy, and 14 of 20 patients
      experienced taste disturbances. Patients reporting more severe taste toxicity
      also reported more severe toxicities with sense of smell (r(2) = 0.60, P < .006).
      Tumor location in the temporal lobe predicted for increased severity of taste
      toxicity (F3, 16 = 1.44, P < .06). The nasopharynx was the only structure in
      which the DVH data predicted the presence of radiation-induced taste changes
      (r(2) = 0.28, P < .02). CONCLUSIONS: Radiation-induced taste toxicity appears to
      be more common in temporal lobe tumors, and may be related to the dose received
      by the nasopharynx.

PMID- 24890355
TI  - Quantification of the impact of multifaceted initiatives intended to improve
      operational efficiency and the safety culture: a case study from an academic
      medical center radiation oncology department.
AB  - PURPOSE: We have systematically been incorporating several operational efficiency
      and safety initiatives into our academic radiation oncology clinic. We herein
      quantify the impact of these initiatives on prospectively collected, clinically
      meaningful, metrics. METHODS AND MATERIALS: The data from 5 quality improvement
      initiatives, each focused on a specific safety/process concern in our clinic, are
      presented. Data was collected prospectively: operational metrics recorded before
      and after implementation of the initiative were compared using statistical
      analysis. Results from the Agency for Health Care Research and Quality (AHRQ)
      patient safety culture surveys administered during and after many of these
      initiatives were similarly compared. RESULTS: (1) Workload levels for nurses
      assisting with brachytherapy were high (National Aeronautics and Space
      Administration Task Load Index (NASA-TLX) scores >55-60, suggesting, "overwork").
      Changes in work flow and procedure room layout reduced workload to more
      acceptable levels (NASA-TLX <55; P < .01). (2) The rate of treatment therapists
      being interrupted was reduced from a mean of 4 (range, 1-11) times per patient
      treatment to a mean <1 (range, 0-3; P < .001) after implementing standards for
      electronic communication and placement of monitors informing patients and staff
      of the treatment machine status (ie, delayed, on time). (3) The rates of replans
      by dosimetrists was reduced from 11% to 6% (P < .01) through a more systematic
      pretreatment peer review process. (4) Standardizing nursing and resident
      functions reduced patient wait times by ~ 45% (14 min; P < .01). (5)
      Standardizing presimulation instructions from the physician reduced the number of
      patients experiencing delays on the simulator (>50% to <10%; P < .01). To assess
      the overall changes in "patient safety culture," we conducted a pre- and
      postanalysis using the AHRQ survey. Improvements in all measured dimensions were
      noted. CONCLUSIONS: Quality improvement initiatives can be successfully
      implemented in an academic radiation oncology department to yield measurable
      improvements in operations resulting in improvement in patient safety culture.

PMID- 24890356
TI  - Planning study and dose measurements of intracranial stereotactic radiation
      surgery with a flattening filter-free linac.
AB  - PURPOSE: Flattening filter-free (FFF) beams have recently become available for
      radiation therapy, offering much higher dose rates but complicating treatment
      owing to the nonflat profile. Stereotactic treatment is one of the most evident
      scenarios to investigate the use of FFF beams. METHODS AND MATERIALS: We present
      a planning study of a FFF 7-MV beam for the treatment of brain metastases using
      multiple noncoplanar arcs. Plan differences as compared with flat 6 MV photon
      fields are estimated using different measures of quality. Absolute dosimetry and
      fluence distribution are verified and the out-of-field dose is measured. RESULTS:
      The FFF 7-MV plans are slightly better than the flat 6-MV plans as evaluated by a
      number of quality indices, dose to organs at risk, and out-of-field dose,
      although differences may not be clinically relevant. Verification does not pose
      any problems. CONCLUSIONS: The FFF 7-MV treatment plans are marginally superior
      to the flat-beam 6-MV plans in almost all cases, with greatly reduced treatment
      times (almost 50%).

PMID- 24890357
TI  - Delaying chemoradiation until after completion of adjuvant chemotherapy for
      pancreatic cancer may not impact local control.
AB  - BACKGROUND: Timing of administration of adjuvant chemoradiation (CRT) for
      pancreatic cancer has varied across studies. To date, the impact of timing of
      adjuvant CRT on long-term outcomes has not been evaluated. This study evaluates
      the effect of timing of adjuvant CRT on locoregional control (LRC) and overall
      survival (OS). METHODS AND MATERIALS: We performed a review of 159 patients with
      resected pancreatic adenocarcinoma who received adjuvant CRT between 1998 and
      2010. Median dose of CRT was 50.4 Gy. The primary study variable was timing of
      CRT, dichotomized as immediate CRT versus delayed CRT. Consistent with Radiation
      Therapy Oncology Group (RTOG) 9704, immediate chemoradiation was defined as after
      <=1 cycle of chemotherapy, whereas delayed CRT was defined as after >1 cycle. Cox
      multivariate analysis (MVA) was performed. RESULTS: Median follow-up was 55
      months. Seventy-four percent of patients received immediate CRT, and 26% patients
      received delayed CRT. Patients treated with delayed CRT were more likely to
      receive adjuvant gemcitabine (100% vs 53%; P < .001). Timing of adjuvant CRT was
      not associated with LRC or OS on univariate or MVA. Preoperative carcinoembryonic
      antigen >=1.3 ng/mL (hazard ratio, 3.18; P = .017) and positive margins (hazard
      ratio, 5.35; P < .001) were associated with lower rates LRC on MVA. Higher lymph
      node positivity ratio and not receiving adjuvant gemcitabine were independently
      associated with worse OS. CONCLUSIONS: Timing of adjuvant CRT for resectable
      pancreatic cancer may not significantly affect LRC or OS. These findings support
      the ongoing RTOG 0848 trial design, and provide reassurance that delaying CRT
      until completion of chemotherapy should not significantly impact LRC.

PMID- 24890358
TI  - Consolidating duodenal and small bowel toxicity data via isoeffective dose
      calculations based on compiled clinical data.
AB  - PURPOSE: To consolidate duodenum and small bowel toxicity data from clinical
      studies with different dose fractionation schedules using the modified linear
      quadratic (MLQ) model. A methodology of adjusting the dose-volume (D,v)
      parameters to different levels of normal tissue complication probability (NTCP)
      was presented. METHODS AND MATERIALS: A set of NTCP model parameters for duodenum
      toxicity were estimated by the chi(2) fitting method using literature-based
      tolerance dose and generalized equivalent uniform dose (gEUD) data. These model
      parameters were then used to convert (D,v) data into the isoeffective dose in 2
      Gy per fraction, (D(MLQED2),v) and convert these parameters to an isoeffective
      dose at another NTCP (D(MLQED2'),v). RESULTS: The literature search yielded 5
      reports useful in making estimates of duodenum and small bowel toxicity. The NTCP
      model parameters were found to be TD50(1)(model) = 60.9 +/- 7.9 Gy, m = 0.21 +/-
      0.05, and delta = 0.09 +/- 0.03 Gy(-1). Isoeffective dose calculations and
      toxicity rates associated with hypofractionated radiation therapy reports were
      found to be consistent with clinical data having different fractionation
      schedules. Values of (D(MLQED2'),v) between different NTCP levels remain
      consistent over a range of 5%-20%. CONCLUSIONS: MLQ-based isoeffective
      calculations of dose-response data corresponding to grade >=2 duodenum toxicity
      were found to be consistent with one another within the calculation uncertainty.
      The (D(MLQED2),v) data could be used to determine duodenum and small bowel dose
      volume constraints for new dose escalation strategies.

PMID- 24890359
TI  - Patterns of practice in radiation therapy for non-small cell lung cancer among
      members of the American Society for Radiation Oncology.
AB  - PURPOSE: To better define patterns of practice for patients with non-small cell
      lung cancer (NSCLC) in the United States. METHODS AND MATERIALS: A survey of 36
      questions was designed to collect information regarding practice patterns of
      radiation oncologists for the management of patients with NSCLC. All American
      Society for Radiation Oncology members were invited to respond. RESULTS: Four
      hundred twenty-four responses from radiation oncologists in the United States
      were received. The response rate for the survey was approximately 20%.
      Substantial discrepancies were seen in the use of stereotactic body radiation
      therapy (SBRT) for patients with peripherally and centrally located early-stage
      tumors and in the recommended SBRT dose. There was a near consensus opinion
      regarding the use of concurrent chemotherapy and the radiation dose for patients
      with inoperable stage II and III NSCLC with a good performance status; however,
      in patients with a poor performance status or in patients with stage IV disease
      treatment recommendations differed remarkably. Additionally, the use of elective
      nodal irradiation and the assessment of tumor motion during simulation were
      highly variable. Thoracic radiation oncologists were more likely to prescribe
      higher doses, omit elective nodal irradiation, and use advanced technologies (P <
      .001). CONCLUSIONS: Substantial variations were seen in the management of
      patients with stage I and IV NSCLC in addition to the incorporation of new
      technology. This information can be used to help design meaningful clinical
      trials.

PMID- 24890361
TI  - Phylogenetic diversity of Fusarium incarnatum-equiseti species complex isolated
      from Spanish wheat.
AB  - Wheat is the most important cereal grown in the European Union and Spain is its
      fifth largest wheat producer. There is little information about Fusarium species
      associated with wheat in Spain. Phylogenetic diversity of 51 strains belonging to
      Fusarium incarnatum-equiseti species complex (FIESC) isolated from Spanish wheat
      was investigated using partial sequences of the translation elongation factor
      gene (EF-1alpha). Maximum-parsimony and Bayesian analysis of aligned DNA
      sequences resolved 18 haplotypes and 7 phylogenetic species. Strains
      morphologically identified as F. equiseti belonged to two different phylogenetic
      species, FIESC-5 and FIESC-14. Some correlation between phylogenetic species and
      geographical region was found. The present results highlight the potential
      contribution of FIESC to the mycotoxin contamination of Spanish wheat. 

PMID- 24890360
TI  - Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone
      oligometastases.
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) is being applied more widely
      for oligometastatic disease. This technique is now being used for non-spine bony
      metastases in addition to liver, spine, and lung. However, there are few studies
      examining the toxicity and outcomes of SBRT for non-spine bone metastases.
      METHODS AND MATERIALS: Between 2008 and 2012, 74 subjects with oligometastatic
      non-spine bony metastases of varying histologies were treated at the Mayo Clinic
      with SBRT. A total of 85 non-spine bony sites were treated. Median local control,
      overall survival, and progression-free survival were described. Acute toxicity
      (defined as toxicity <90 days) and late toxicity (defined as toxicity >=90 days)
      were reported and graded as per standardized Common Toxicity Criteria for Adverse
      Events 4.0 criteria. RESULTS: The median age of patients treated was 60 years.
      The most common histology was prostate cancer (31%) and most patients had fewer
      than 3 sites of disease at the time of simulation (64%). Most of the non-spine
      bony sites lay within the pelvis (65%). Dose and fractionation varied but the
      most common prescription was 24 Gy/1 fraction. Local recurrence occurred in 7
      patients with a median time to failure of 2.8 months. Local control was 91.8% at
      1 year. With a median follow-up of 7.6 months, median SBRT specific overall
      survival and progression-free survival were 9.3 months and 9.7 months,
      respectively. Eighteen patients developed acute toxicity (mostly grade 1 and 2
      fatigue and acute pain flare); 9 patients developed grade 1-2 late toxicities.
      Two patients developed pathologic fractures but both were asymptomatic. There
      were no late grade 3 or 4 toxicities. CONCLUSIONS: Stereotactic body radiation
      therapy is a feasible and tolerable treatment for non-spine bony metastases.
      Longer follow-up will be needed to accurately determine late effects.

PMID- 24890362
TI  - The protective effect of heat shock protein 70 (Hsp70) in atrial fibrillation in
      various cardiomyopathy conditions.
AB  - Heat shock proteins (Hsp) protect myocardial cells from acute stress such as
      atrial fibrillation (AF) and also from the chronic stress. It is not understood
      that Hsp70 can prevent AF under cardiomyopathy (CM) conditions. Therefore, we
      hypothesized that Hsp70 might beneficially influence on the occurrence of AF in
      CM conditions. We purposed to investigate the correlation between Hsp70 and the
      AF inducibility in various CM conditions that are unclear. We constructed four
      different animal models using Sprague-Dawley rats: an ischemic CM group (n = 12),
      a non-ischemic dilated CM group (n = 12), a pressure-overload hypertrophic CM
      group (n = 12), and a sham group (CON, n = 12). After 4-6 weeks of intervention
      animals, AF was induced acutely prior to hemodynamic studies. Hemodynamic data
      using the Langendorff technique and histologic evaluation were conducted
      sequentially in all animal groups. Afterwards, levels of Hsp70 were measured from
      atrial tissues by real-time polymerase chain reaction study. The hemodynamic data
      and histologic studies proved that each animal model was suitable to this study
      protocol. All CM groups showed that Hsp70 was elevated significantly compared to
      the control groups (P < 0.005). Among these CM groups, the TAC group revealed
      lower Hsp70 levels and higher induction rates of atrial fibrillation than the
      other groups (P < 0.005). The level of Hsp70 was elevated in all the CM models
      and it was negatively correlated with AF induction rate in sham group. However,
      we could not find correlation between Hsp70 and AF among the CM models. 

PMID- 24890364
TI  - Familial carotenaemia and carotenoderma.

PMID- 24890363
TI  - Emergency department and outpatient treatment of acute injuries in older adults
      in the United States: 2009-2010.
AB  - OBJECTIVES: We sought to describe epidemiological patterns of acute injuries
      treated in emergency department (ED) and outpatient primary care settings in the
      United States. DESIGN: Retrospective cross-sectional analysis of data from the
      2009 and 2010 National Health Care Surveys. SETTING: Emergency departments and
      outpatient primary care clinics. PARTICIPANTS: Older adults (>= 65) with initial
      visits for acute injuries. MEASUREMENTS: Frequencies and incidence rates of
      medically attended injury according to participant characteristics and care
      setting. RESULTS: Of the 19.7 million medically attended acute injuries in older
      adults in 2009-10, 50% were treated at EDs and 50% at outpatient primary care
      clinics. The annual incidence rate of medically attended injuries rose with age,
      from 20.8 (95% confidence interval (CI) = 17.0-24.6) per 100 in those aged 65 to
      74 to 41.5 (95% CI = 33.5-49.4) per 100 for those aged 85 and older. Of injury
      related ED visits, 60% occurred outside standard business hours, 36% were triaged
      as low acuity, and 25% resulted in admission. Only 9% of injury-related primary
      care visits had injury prevention counseling documented. CONCLUSION: Medically
      attended injuries area common in older adults, and their incidence increases with
      advancing age. Half of all initial visits for acute injuries in older adults are
      to primary care clinics. Most injured individuals are discharged home, and injury
      prevention counseling is rarely documented. To inform injury prevention efforts
      appropriately and to avoid underestimating the burden of injury, future injury
      studies should include a range of outpatient and inpatient care settings.

PMID- 24890365
TI  - Congenital heart disease in men - birth characteristics and reproduction: a
      national cohort study.
AB  - BACKGROUND: Women with congenital heart disease (CHD) are more often born preterm
      or small-for-gestational age and with a caesarean section. This pattern together
      with an increased risk of congenital anomalies seems to be repeated in the next
      generation. Information on the effect of paternal CHD on their offspring is
      sparse. In this study we investigated if men with CHD differ from those who do
      not have CHD with respect to characteristics related to their own births, their
      reproductive patterns and the neonatal outcomes of their children. METHODS: In
      this national cohort study data were derived from Swedish population-based
      registries. The population consists of all men born in 1973-1983 who were alive
      and living in Sweden at 13 years of age (n = 522 216). The index group is men
      with CHD (n = 2689). Men diagnosed with CHD were compared with men without CHD.
      The CHD were also divided into two groups, complex and simple CHD and comparisons
      between the groups were made. RESULTS: Men with CHD are more likely to have been
      born preterm (p < 0.001), small-for gestational-age (p < 0.001) or large-for
      gestational-age (p < 0.001) than men without CHD. They are also more likely to
      have been the result of a twin pregnancy (p < 0.001) and to have been delivered
      by caesarean section (p < 0.001). Men with CHD have a decreased likelihood to
      become fathers compared to non-CHD men and in this study their offspring do not
      have a higher incidence of CHD than offspring to non-CHD fathers. The neonatal
      outcomes of children of men with CHD do not differ from the outcomes of children
      of non-CHD men. CONCLUSIONS: Men with CHD were more often born with non-optimal
      characteristics compared to men without the condition. However, the increased
      risk does not repeat itself in the next generation. This knowledge can lead to
      improved preconception counselling for couples in which the father has a CHD.

PMID- 24890371
TI  - Monolithically integrated spinel M(x)Co(3-x)O(4) (M=Co, Ni, Zn) nanoarray
      catalysts: scalable synthesis and cation manipulation for tunable low-temperature
      CH(4) and CO oxidation.
AB  - A series of large scale Mx Co3-x O4 (M=Co, Ni, Zn) nanoarray catalysts have been
      cost-effectively integrated onto large commercial cordierite monolithic
      substrates to greatly enhance the catalyst utilization efficiency. The
      monolithically integrated spinel nanoarrays exhibit tunable catalytic performance
      (as revealed by spectroscopy characterization and parallel first-principles
      calculations) toward low-temperature CO and CH4 oxidation by selective cation
      occupancy and concentration, which lead to controlled adsorption-desorption
      behavior and surface defect population. This provides a feasible approach for
      scalable fabrication and rational manipulation of metal oxide nanoarray catalysts
      applicable at low temperatures for various catalytic reactions. 

PMID- 24890370
TI  - Catalytic activity of a novel serine/threonine protein phosphatase PP5 from
      Leishmania major.
AB  - Leishmaniasis is a vector-borne disease caused by protozoan parasites of the
      genus Leishmania. Our knowledge of protein phosphatases (PPs) and their
      implication in signaling events is very limited. Here we report the expression,
      characterization and mutagenesis analysis of a novel protein phosphatase 5 (PP5)
      in Leishmania major. Recombinant PP5 is a bona fide phosphatase and is
      enzymatically active. Site-directed mutagenesis revealed auto-inhibitory roles of
      the N-terminal region. This is a rational first approach to understand the role
      of PP5 in the biology of the parasite better as well as its potential future
      applicability to anti-parasitic intervention. 

PMID- 24890366
TI  - Gambogic acid suppresses hypoxia-induced hypoxia-inducible factor-1alpha/vascular
      endothelial growth factor expression via inhibiting phosphatidylinositol 3
      kinase/Akt/mammalian target protein of rapamycin pathway in multiple myeloma
      cells.
AB  - In multiple myeloma (MM), the hypoxic environment is an important factor causing
      tumor angiogenesis, which is strongly correlated to disease progression and
      unfavorable outcome by activating the key transcription factor, hypoxia-inducible
      factor-1alpha (HIF-1alpha). Gambogic acid (GA) is the major active ingredient of
      gamboge, which has been shown to possess antitumor effect by in vitro and in vivo
      study. However, the underlying molecular mechanism of whether GA inhibits tumor
      angiogenesis remains poorly understood. In this study, we investigated the
      effects of GA on expression of HIF-1alpha, and its downstream target gene
      vascular endothelial growth factor (VEGF) in human MM U266 cells. We found that
      hypoxia induced increase in the level of HIF-1alpha subunit protein and activated
      the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target protein of
      rapamycin (mTOR) pathway. Moreover, the treatment with GA markedly decreased HIF
      1alpha and VEGF expression under hypoxic conditions. Mechanistic studies
      exhibited that GA inhibited the production of HIF-1alpha by reducing
      phosphorylation of Akt and mTOR in U266 cells. Furthermore, in vivo study
      revealed that intravenous injection of GA once every other day for 2 weeks could
      suppress tumor volumes by antiangiogenesis activity. Taken together, our results
      identify that GA suppresses hypoxia-activated pathways that are linked to MM
      progression, at least partly, by the inhibition of the PI3K/Akt/mTOR signaling
      pathway. Therefore, GA may be a new potent therapeutic agent against human MM
      cells.

PMID- 24890372
TI  - Pipeliner: software to evaluate the performance of bioinformatics pipelines for
      next-generation resequencing.
AB  - The choice of technology and bioinformatics approach is critical in obtaining
      accurate and reliable information from next-generation sequencing (NGS)
      experiments. An increasing number of software and methodological guidelines are
      being published, but deciding upon which approach and experimental design to use
      can depend on the particularities of the species and on the aims of the study.
      This leaves researchers unable to produce informed decisions on these central
      questions. To address these issues, we developed pipeliner - a tool to evaluate,
      by simulation, the performance of NGS pipelines in resequencing studies.
      Pipeliner provides a graphical interface allowing the users to write and test
      their own bioinformatics pipelines with publicly available or custom software. It
      computes a number of statistics summarizing the performance in SNP calling,
      including the recovery, sensitivity and false discovery rate for heterozygous and
      homozygous SNP genotypes. Pipeliner can be used to answer many practical
      questions, for example, for a limited amount of NGS effort, how many more
      reliable SNPs can be detected by doubling coverage and halving sample size or
      what is the false discovery rate provided by different SNP calling algorithms and
      options. Pipeliner thus allows researchers to carefully plan their study's
      sampling design and compare the suitability of alternative bioinformatics
      approaches for their specific study systems. Pipeliner is written in C++ and is
      freely available from http://github.com/brunonevado/Pipeliner. 

PMID- 24890375
TI  - Oral prophylaxis as an adjunct procedure towards prevention and management of
      oral cancer: rationale and application.

PMID- 24890374
TI  - Long-term artificial selection reveals a role of TCTP in autophagy in mammalian
      cells.
AB  - Understanding genomic variation and detecting selection signatures in a genome
      under selection have been great challenges for a century. Activation,
      development/exhaustion of primordial follicles in mammalian ovary determines
      reproductive success, menopause/end of female reproductive life. However,
      molecular mechanisms underlying oogenesis, particularly under artificial
      selection, are largely unknown. We report that a proteome-wide scan for selection
      signatures in the genome over 9,000 years of artificial pressure on the ovary
      revealed a general picture of selection signatures in the genome, especially
      genomic variations through artificial selection were detected in promoter and
      intron regions. Crossbreeding between domestic and wild species results in more
      than half of the protein spots exhibiting heterosis. Translationally controlled
      tumor protein (TCTP) is upregulated by artificial selection and positively
      regulates autophagy through the AMP-activated protein kinase pathway. Notably,
      TCTP interacts with ATG16 complex. In addition to cytoplasmic autophagy,
      nucleophagy occurs in the nuclei of granulosa and cumulus cells in ovaries,
      indicating an importance of the nuclear material for degradation by nucleophagy.
      Our findings provide insight into cellular and molecular mechanisms relevant for
      improvement of ovary functions, and identify selection signatures in the genome
      for ovary function over long-term artificial selection pressure. 

PMID- 24890373
TI  - Down-regulating annexin gene GhAnn2 inhibits cotton fiber elongation and
      decreases Ca2+ influx at the cell apex.
AB  - Cotton fiber is a single cell that differentiates from the ovule epidermis and
      undergoes synchronous elongation with high secretion and growth rate. Apart from
      economic importance, cotton fiber provides an excellent single-celled model for
      studying mechanisms of cell-growth. Annexins are Ca(2+)- and phospholipid-binding
      proteins that have been reported to be localized in multiple cellular
      compartments and involved in control of vesicle secretions. Although several
      annexins have been found to be highly expressed in elongating cotton fibers,
      their functional roles in fiber development remain unknown. Here, 14 annexin
      family members were identified from the fully sequenced diploid G. raimondii (D5
      genome), half of which were expressed in fibers of the cultivated tetraploid
      species G. hirsutum (cv. YZ1). Among them, GhAnn2 from the D genome of the
      tetraploid species displayed high expression level in elongating fiber. The
      expression of GhAnn2 could be induced by some phytohormones that play important
      roles in fiber elongation, such as IAA and GA3. RNAi-mediated down-regulation of
      GhAnn2 inhibited fiber elongation and secondary cell wall synthesis, resulting in
      shorter and thinner mature fibers in the transgenic plants. Measurement with non
      invasive scanning ion-selective electrode revealed that the rate of Ca(2+) influx
      from extracellular to intracellular was decreased at the fiber cell apex of
      GhAnn2 silencing lines, in comparison to that in the wild type. These results
      indicate that GhAnn2 may regulate fiber development through modulating Ca(2+)
      fluxes and signaling. 

PMID- 24890376
TI  - Muscle function in Turner syndrome: normal force but decreased power.
AB  - OBJECTIVE: Although hypogonadism and SHOX gene haploinsufficiency likely cause
      the decreased bone mineral density and increased fracture rate associated with
      Turner syndrome (TS), the exact mechanism remains unclear. We tested the
      hypothesis that muscle dysfunction in patients with TS contributes to increased
      fracture risk. The secondary aim was to determine whether menarche, hormone
      therapy duration, positive fracture history and genotype influence muscle
      function parameters in patients with TS. DESIGN: A cross-sectional study was
      conducted in a single university hospital referral centre between March 2012 and
      October 2013. PATIENTS: Sixty patients with TS (mean age of 13.7 +/- 4.5 years)
      were compared to the control group of 432 healthy girls. MEASUREMENTS: A Leonardo
      Mechanograph((r)) Ground Reaction Force Platform was used to assess muscle force
      (Fmax ) by the multiple one-legged hopping test and muscle power (Pmax ) by the
      single two-legged jump test. RESULTS: While the Fmax was normal (mean weight
      specific Z-score of 0.11 +/- 0.77, P = 0.27), the Pmax was decreased in patients
      with TS (Z-score of -0.93 +/- 1.5, P < 0.001) compared with healthy controls. The
      muscle function parameters were not significantly influenced by menarcheal stage,
      hormone therapy duration, fracture history or genotype (linear regression
      adjusted for age, weight and height; P > 0.05 for all). CONCLUSION: Fmax , a
      principal determinant of bone strength, is normal in patients with TS. Previously
      described changes in bone quality and structure in TS are thus not likely related
      to inadequate mechanical loading but rather represent a primary bone deficit. A
      decreased Pmax indicates impaired muscle coordination in patients with TS.

PMID- 24890377
TI  - Influence of joint position on synergistic muscle activity after fatigue of a
      single muscle head.
AB  - INTRODUCTION: We investigated synergistic muscle activity after fatigue of a
      single muscle in different joint positions. METHODS: Two experimental groups (n =
      12 each) performed maximal voluntary contractions (MVCs) before and after
      fatiguing the gastrocnemius lateralis (GL), using neuromuscular electrical
      stimulation (NMES). Neuromuscular tests, including muscle activity during MVC, H
      reflex, and twitch interpolation, were performed. One group completed the
      experiment in a knee-extended position with the second group in a knee-flexed
      position. RESULTS: In the knee-flexed position, the muscle activity increased in
      non-stimulated synergistic muscles. In contrast, in the knee-extended position,
      muscle activity of the synergistic muscles remained unaltered. The MVC force
      remained unaltered in the flexed position and decreased in the extended position.
      CONCLUSIONS: Synergistic muscles compensate for the fatigued muscle in the flexed
      position but not in the extended position. Compensation mechanisms seem to depend
      on joint position.

PMID- 24890378
TI  - A novel clinically relevant segmentation method and corresponding maximal
      ischemia score to risk-stratify patients undergoing myocardial perfusion
      scintigraphy.
AB  - BACKGROUND: Myocardial perfusion scintigraphy (MPS) represents a key prognostic
      tool, but its predictive yield is far from perfect. We developed a novel
      clinically relevant segmentation method and a corresponding maximal ischemia
      score (MIS) in order to risk-stratify patients undergoing MPS. METHODS: Patients
      referred for MPS were identified, excluding those with evidence of myocardial
      necrosis or prior revascularization. A seven-region segmentation approach was
      adopted for left ventricular myocardium, with a corresponding MIS distinguishing
      five groups (no, minimal, mild, moderate, or severe ischemia). The association
      between MIS and clinical events was assessed at 1 year and at long-term follow
      up. RESULTS: A total of 8,714 patients were included, with a clinical follow-up
      of 31 +/- 20 months. Unadjusted analyses showed that subjects with a higher MIS
      were significantly different for several baseline and test data, being older,
      having lower ejection fraction, and achieving lower workloads (P < .05 for all).
      Adverse outcomes were also more frequent in patients with higher levels of
      ischemia, including cardiac death, myocardial infarction (MI), and their
      composites (P < .05 for all). Differences in adverse events remained significant
      even after extensive multivariable adjustment (hazard ratio for each MIS
      increment = 1.57 [1.29-1.90], P < .001 for cardiac death; 1.19 [1.04-1.36], P =
      .013 for MI; 1.23 [1.09-1.39], P = .001 for cardiac death/MI). CONCLUSIONS: Our
      novel segmentation method and corresponding MIS efficiently yield satisfactory
      prognostic information.

PMID- 24890380
TI  - Paper-based silver-nanowire electronic circuits with outstanding electrical
      conductivity and extreme bending stability.
AB  - Here a facile, green and efficient printing-filtration-press (PFP) technique is
      reported for room-temperature (RT) mass-production of low-cost, environmentally
      friendly, high performance paper-based electronic circuits. The as-prepared
      silver nanowires (Ag-NWs) are uniformly deposited at RT on a pre-printed paper
      substrate to form high quality circuits via vacuum filtration and pressing. The
      PFP circuit exhibits more excellent electrical property and bending stability
      compared with other flexible circuits made by existing techniques. Furthermore,
      practical applications of the PFP circuits are demonstrated. 

PMID- 24890379
TI  - Early diabetes treatment does not prevent sympathetic dysinnervation in the
      streptozotocin diabetic rat heart.
AB  - BACKGROUND: Positron emission tomography (PET) studies have demonstrated reduced
      sympathetic neuronal integrity in high-fat diet fed streptozotocin insulin
      resistant diabetic rats in parallel with abnormal early-to-atrial transmitral
      velocity. We hypothesized that administration of anti-glycemic drugs early after
      diabetes induction would prevent sympathetic neuronal dysfunction. METHODS AND
      RESULTS: Male Sprague-Dawley rats fed high-fat diet were administered
      streptozotocin (45 mg.kg(-1), ip, n = 23) to induce diabetes or vehicle alone (n
      = 6). Diabetic rats were randomized to receive insulin (4 U.day(-1)), metformin
      (650 mg.kg(-1).day(-1)), rosiglitazone (4 mg.kg(-1).day(-1)), or no treatment 1
      week after streptozotocin. Small animal PET imaging using the norepinephrine
      analog [(11)C]meta-hydroxyephedrine (HED) at baseline and 8 weeks of diabetes
      determined sympathetic neuronal integrity. Echocardiography assessed cardiac
      function. Plasma norepinephrine levels were determined in parallel. Ex vivo
      immunoblotting was performed at the end of the experiment to compare the relative
      expression of various proteins involved in metabolic and noradrenergic signaling.
      Insulin restored blood glucose and lipid levels to normal. Despite improved
      plasma lipid levels, neither metformin nor rosiglitazone reduced blood glucose.
      At 8 weeks, untreated and treated diabetics displayed a 39%-42% reduction in
      myocardial HED standardized uptake values (P < .05). In all diabetic groups,
      plasma norepinephrine was elevated (2.3- to 3.3-fold, P < .05) and norepinephrine
      reuptake transporter expression reduced (28%-35%, P < .05) compared to non
      diabetics. Doppler echocardiography revealed delayed development of prolonged
      mitral valve deceleration and elevated early-to-atrial filling velocity ratio
      among treated diabetic rats. CONCLUSION: Early glycemic treatment of insulin
      resistant diabetic rats did not prevent deterioration of sympathetic neuronal
      integrity though ventricular filling abnormalities were delayed.

PMID- 24890381
TI  - Turnip rapeseed does not worsen atopic eczema in most sensitized children.

PMID- 24890383
TI  - Chemical composition, antimicrobial and antibiofilm activity of the essential oil
      and methanol extract of the Mediterranean cypress (Cupressus sempervirens L.).
AB  - BACKGROUND: Cupressus sempervirens is a medicinal plant traditional, its dried
      leaves are used in treatment of stomach pain, diabetes, inflammation, toothache,
      laryngitis and as contraceptive. METHODS: The present study was conducted to
      evaluate the in vitro antimicrobial, antibiofilm and determination chemical
      contents of the essential oil (Eo) and methanol extract from Mediterranean C.
      sempervirens L. The chemical composition of a hydrodistilled Eo of C.
      sempervirens was analyzed by a GC and GC/MS system. RESULTS: A total of 20
      constituents representing 98.1% of the oil were identified: alpha-pinene (48.6%),
      delta-3-carene (22.1%), limonene (4.6%) and alpha-terpinolene (4.5%) were the
      main components comprising 79.8% of the oil. The antimicrobial test results
      showed that the methanol extract of C. sempervirens strongly inhibited the growth
      of the test bacteria studied, except for yeast species while the Eo had moderate
      antibacterial, but no anti-candida activity. Klebsiella pneumoniae was proven to
      be the most susceptible against methanol extract. The exposure time of Eo and
      methanol extract for complete inhibition of cell viability of K. pneumoniae was
      found to be 250 MUg at 30 min and 500 MUg at 120 min, respectively. The
      antibiofilm potential of the samples was evaluated using methods of PVC
      microtiter and eradication on biomaterial. Visual results showed visible biofilm
      eradication from the surface of intravenous infusion tube at 500 MUg of Eo and
      methanol extract. CONCLUSIONS: The results presented here may suggest that the Eo
      and extracts of C. sempervirens possess antimicrobial and antibiofilm properties,
      and therefore, can be used as natural preservative ingredients in food and/or
      pharmaceuticals.

PMID- 24890382
TI  - T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2
      overexpressing uterine serous carcinoma in vitro and in vivo.
AB  - Amplification of c-erbB2 has been reported in over 30% of uterine serous
      carcinoma (USC) and found to confer poor survival because of high proliferation
      and increased resistance to therapy. In this study, we evaluated for the first
      time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against
      multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro
      followed by developing a supportive in vivo model. Fifteen primary USC cell lines
      were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein
      expression. C-erbB2 gene amplification was evaluated using fluorescent in situ
      hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody
      dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release
      assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow
      cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC
      xenografts in SCID mice was also evaluated. High levels of HER2 protein
      overexpression and HER2 gene amplification were detected in 33% of USC cell
      lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell
      proliferation and in causing apoptosis (P = 0.004) of USC showing HER2
      overexpression. Importantly, T-DM1 was highly active at reducing tumor formation
      in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with
      TDM-1 had significantly longer survival when compared to T-treated mice and
      control mice (P <= 0.0001). T-DM1 shows promising antitumor effect in HER2
      positive USC cell lines and USC xenografts and its activity is significantly
      higher when compared to T. T-DM1 may represent a novel treatment option for HER2
      positive USC patients with disease refractory to trastuzumab and traditional
      chemotherapy. 

PMID- 24890384
TI  - Stability of bovine lactoferrin in luminal extracts and mucosal homogenates from
      rat intestine: a prelude to oral absorption.
AB  - Oral delivery is the most common method for bovine lactoferrin (bLf)
      administration. However, the presence of proteolytic enzymes in the stomach and
      intestine limits the effective absorption of bLf within the gastrointestinal (GI)
      tract. To determine the extent of bLf proteolysis, several digestion models were
      developed using luminal extracts and mucosal homogenates isolated from four
      regions of rat intestine: duodenum, jejunum, ileum, and proximal colon. The
      kinetics of bLf degradation followed a pseudo-first-order rate, and almost
      complete hydrolysis of bLf was observed in the luminal extracts, indicating that
      bLf is more susceptive to luminal peptidases rather than mucosal enzymes.
      Moreover, a significant reduction in bLf proteolysis was observed in the presence
      of soybean trypsin inhibitor (SBTI), bestatin, and bacitracin, suggesting that
      there exist trypsin-like and aminopeptidase-like proteases, which play a key role
      in the degradation of bLf in the intestine. Lactoferrin was then encapsulated in
      several lipid-based delivery systems including liposomes and solid lipid
      particles (SLPs) with polymer modification, showing at least 50% of intact bLf
      remaining after 6 h of digestion compared with native bLf. These findings suggest
      that particle encapsulation may modulate protein digestion and possibly achieve
      sufficient oral bioavailability of bLf.

PMID- 24890386
TI  - The use of eutectic mixture of lidocaine and prilocaine in mice (Mus musculus)
      for tail vein injections.
AB  - OBJECTIVE: To investigate a topical local anesthesia technique as a means to
      prevent and/or diminish pain in mice in a laboratory setting associated with tail
      vein injections performed by personnel in training. STUDY DESIGN: Prospective,
      randomized experimental trial. ANIMALS: Thirty six adult female, 23-28 g CD-1
      mice from an in-house training colony. They were acclimated to routine training
      and handling classes. METHODS: Eutectic mixture of local anesthetics (EMLA) cream
      (2.5% lidocaine/2.5% prilocaine) or a bland ointment control (n = 18) was applied
      on the tail prior to intravenous injection. The injections were performed by
      novices, who had never attempted the procedure, and experienced personnel. All
      participants were blinded to treatment groups. Three injection attempts were
      allowed per animal. The mice were observed and scored by blinded evaluators for
      behavioral and physiological changes, including respiratory rate, vocalization,
      tail flick, and escape behaviors, during and after the injection. RESULTS: This
      study demonstrates that aversive behaviors induced by lateral tail vein injection
      were not changed by the preemptive application of EMLA cream. The aversive
      behaviors associated with lateral tail vein injection were significantly affected
      by the number of injection attempts and the individual's experience level.
      CONCLUSIONS AND CLINICAL RELEVANCE: Topical EMLA cream did not reduce signs of
      aversive reaction to tail vein injection and thus we did not find support for its
      use in mouse training programs for tail vein injections.

PMID- 24890385
TI  - An integrated genomic approach identifies persistent tumor suppressive effects of
      transforming growth factor-beta in human breast cancer.
AB  - INTRODUCTION: Transforming growth factor-betas (TGF-betas) play a dual role in
      breast cancer, with context-dependent tumor-suppressive or pro-oncogenic effects.
      TGF-beta antagonists are showing promise in early-phase clinical oncology trials
      to neutralize the pro-oncogenic effects. However, there is currently no way to
      determine whether the tumor-suppressive effects of TGF-beta are still active in
      human breast tumors at the time of surgery and treatment, a situation that could
      lead to adverse therapeutic responses. METHODS: Using a breast cancer progression
      model that exemplifies the dual role of TGF-beta, promoter-wide chromatin
      immunoprecipitation and transcriptomic approaches were applied to identify a core
      set of TGF-beta-regulated genes that specifically reflect only the tumor
      suppressor arm of the pathway. The clinical significance of this signature and
      the underlying biology were investigated using bioinformatic analyses in clinical
      breast cancer datasets, and knockdown validation approaches in tumor xenografts.
      RESULTS: TGF-beta-driven tumor suppression was highly dependent on Smad3, and
      Smad3 target genes that were specifically enriched for involvement in tumor
      suppression were identified. Patterns of Smad3 binding reflected the preexisting
      active chromatin landscape, and target genes were frequently regulated in
      opposite directions in vitro and in vivo, highlighting the strong contextuality
      of TGF-beta action. An in vivo-weighted TGF-beta/Smad3 tumor-suppressor signature
      was associated with good outcome in estrogen receptor-positive breast cancer
      cohorts. TGF-beta/Smad3 effects on cell proliferation, differentiation and ephrin
      signaling contributed to the observed tumor suppression. CONCLUSIONS: Tumor
      suppressive effects of TGF-beta persist in some breast cancer patients at the
      time of surgery and affect clinical outcome. Carefully tailored in vitro/in vivo
      genomic approaches can identify such patients for exclusion from treatment with
      TGF-beta antagonists.

PMID- 24890388
TI  - Grape anthocyanin oligomerization: a putative mechanism for red color
      stabilization?
AB  - The equilibrium forms of malvidin-3-O-glucoside trimer present in grape skins
      were studied in aqueous solution at different pH values through UV-Visible
      spectroscopy. It was observed that the reactivity of this compound is strongly
      dominated by acid-base chemistry (pKa1=3.61+/-0.03; pKa2=6.83+/-0.06), with the
      reaction sequence hydration-tautomerization-isomerization accounting less than
      10% of the overall reactivity. The decrease of hydration of this flavylium cation
      derivative when compared to the original anthocyanins results from the formation
      of a cluster of the pigment with a high-energy of solvation that inhibits the
      access of water molecules to the flavylium cation core preventing by this way the
      hydration reactions. Overall of these results raise the hypothesis that
      polymerization may be a natural stabilization mechanism for the red color of
      anthocyanins. 

PMID- 24890387
TI  - PMD patient mutations reveal a long-distance intronic interaction that regulates
      PLP1/DM20 alternative splicing.
AB  - Alternative splicing of the proteolipid protein 1 gene (PLP1) produces two forms,
      PLP1 and DM20, due to alternative use of 5' splice sites with the same acceptor
      site in intron 3. The PLP1 form predominates in central nervous system RNA.
      Mutations that reduce the ratio of PLP1 to DM20, whether mutant or normal protein
      is formed, result in the X-linked leukodystrophy Pelizaeus-Merzbacher disease
      (PMD). We investigated the ability of sequences throughout PLP1 intron 3 to
      regulate alternative splicing using a splicing minigene construct transfected
      into the oligodendrocyte cell line, Oli-neu. Our data reveal that the alternative
      splice of PLP1 is regulated by a long-distance interaction between two highly
      conserved elements that are separated by 581 bases within the 1071-base intron 3.
      Further, our data suggest that a base-pairing secondary structure forms between
      these two elements, and we demonstrate that mutations of either element designed
      to destabilize the secondary structure decreased the PLP1/DM20 ratio, while swap
      mutations designed to restore the structure brought the PLP1/DM20 ratio to near
      normal levels. Sequence analysis of intron 3 in families with clinical symptoms
      of PMD who did not have coding-region mutations revealed mutations that
      segregated with disease in three families. We showed that these patient
      mutations, which potentially destabilize the secondary structure, also reduced
      the PLP1/DM20 ratio. This is the first report of patient mutations causing
      disease by disruption of a long-distance intronic interaction controlling
      alternative splicing. This finding has important implications for molecular
      diagnostics of PMD. 

PMID- 24890389
TI  - Membrane-forming lipids of wild halophytes growing under the conditions of
      Prieltonie of South Russia.
AB  - The composition of membrane-forming lipids has been examined for 10 wild
      halophyte species growing in southern Russian on alkaline soil. The plants belong
      to seven taxa of family rank: by their life form, which are semi-shrubs,
      herbaceous annuals, and perennial plants; their salt tolerance, which are
      classified as the euhalophytes, crynohalophytes, and glycohalophytes; and by
      their sensitivity to water, classifications of mesoxerophytes and xeromesophytes.
      Parallels have been found between the lipid composition and the ecological status
      of the plants. It has also been revealed that the similarity in the glyco- and
      phospholipid composition of different plant groups relates to the water factor
      and the type of salt accumulation, respectively. The fatty acid compositions of
      the examined plants is determined at the species level. 

PMID- 24890390
TI  - Guaiane sesquiterpenes and isopimarane diterpenes from an endophytic fungus
      Xylaria sp.
AB  - Nine oxygenated guaiane-type sesquiterpenes and three isopimarane diterpenes were
      isolated from the culture broth of an endophytic fungus, Xylaria sp. YM 311647,
      obtained from Azadirachta indica. The structures of these compounds were
      elucidated by interpretation of spectroscopic data. The absolute configurations
      of two of these were confirmed by X-ray crystallographic analysis. All of the
      compounds were tested for their antifungal activities against five pathogenic
      fungal cells. The results showed that nine sesquiterpenes were moderately active
      against Candida albicans and Hormodendrum compactum with MIC values ranging from
      32 to 256MUg/ml, while the diterpenes were more active; One of these exhibited
      the most potent inhibitory activity against C. albicans and Pyricularia oryzae
      with MIC values of 16MUg/ml. 

PMID- 24890391
TI  - New reliable scoring system, Toyama mouse score, to evaluate locomotor function
      following spinal cord injury in mice.
AB  - BACKGROUND: Among the variety of methods used to evaluate locomotor function
      following a spinal cord injury (SCI), the Basso Mouse Scale score (BMS) has been
      widely used for mice. However, the BMS mainly focuses on hindlimb movement rather
      than on graded changes in body support ability. In addition, some of the scoring
      methods include double or triple criteria within a single score, which likely
      leads to an increase in the deviation within the data. Therefore we aimed to
      establish a new scoring method reliable and easy to perform in mice with SCI.
      FINDINGS: Our Toyama Mouse Score (TMS) was established by rearranging and
      simplifying the BMS score and combining it with the Body Support Scale score
      (BSS). The TMS reflects changes in both body support ability and hindlimb
      movement. The definition of single score is made by combing multiple criteria in
      the BMS. The ambiguity was improved in the TMS. Using contusive SCI mice,
      hindlimb function was measured using the TMS, BMS and BSS systems. The TMS could
      distinguish changes in hindlimb movements that were evaluated as the same score
      by the BMS. An analysis of the coefficient of variation (CV) of score points
      recorded for 11 days revealed that the CV for the TMS was significantly lower
      than the CV obtained using the BMS. A variation in intra evaluators was lower in
      the TMS than in the BMS. CONCLUSION: These results suggest that the TMS may be
      useful as a new reliable method for scoring locomotor function for SCI models.

PMID- 24890392
TI  - Global implications of China's healthcare reform.
AB  - The ongoing healthcare reform in China has a powerful spillover effect beyond the
      health sector and the borders of China. A successful completion of the Chinese
      reform will offer a new model for social justice development, shift the global
      economy toward sustainability and create a new hub for science and technology in
      medical and health science. However, reforming the healthcare system in the most
      populated country is a daunting task. China will not live up to its promise, and
      all the potentials may end with hype not hope if coherent national strategies are
      not constructed and state-of-the-art navigation is not achieved with staggering
      domestic and global challenges. The cost of failure will be immensely high,
      socioeconomic costs for Chinese and an opportunity cost for the world as a whole.
      A full appreciation of the global implications of China's healthcare reform is
      crucial in keeping China receptive toward good practices evidence-approved
      elsewhere and open minded to fulfill its international obligations. More
      critically, the appreciation yields constructive engagements from global
      community toward a joint development and global prosperity. The current report
      provides a multiple disciplinary assessment on the global implications of the
      healthcare reform in China.

PMID- 24890393
TI  - Treating infections caused by carbapenemase-producing Enterobacteriaceae.
AB  - Carbapenemase-producing Enterobacteriaceae (CPE) have spread worldwide, causing
      serious infections with increasing frequency. CPE are resistant to almost all
      available antibiotics, complicating therapy and limiting treatment options.
      Mortality rates associated with CPE infections are unacceptably high, indicating
      that the current therapeutic approaches are inadequate and must be revised. Here,
      we review 20 clinical studies (including those describing the largest cohorts of
      CPE-infected patients) that provided the necessary information regarding isolate
      and patient characteristics and treatment schemes, as well as a clear assessment
      of outcome. The data summarized here indicate that treatment with a single in
      vitro active agent resulted in mortality rates not significantly different from
      that observed in patients treated with no active therapy, whereas combination
      therapy with two or more in vitro active agents was superior to monotherapy,
      providing a clear survival benefit (mortality rate, 27.4% vs. 38.7%; p <0.001).
      The lowest mortality rate (18.8%) was observed in patients treated with
      carbapenem-containing combinations.

PMID- 24890394
TI  - How do 9-month-old infants categorize human and ape faces? A rapid repetition ERP
      study.
AB  - The current study investigates how infants categorize human compared to ape
      faces. Nine-month-old infants were presented with priming stimuli related to
      human (N = 24) or ape (N = 25) face targets on different levels of
      categorization. Event-related potentials were recorded during a passive-looking
      rapid repetition paradigm. In a within-subjects design, priming effects of the
      same faces, different faces from the same basic-level category, different faces
      from the other basic-level category (human/ape faces), and house fronts were
      examined. Human and ape faces were first categorized on a superordinate level
      ("faces"), as indicated by enhanced P1 amplitude and reduced P1 latency for faces
      primed by any faces. Then, human and ape faces were categorized on a basic level.
      N290 amplitude and latency were larger for human and monkey targets primed by
      human faces. Neither human nor ape faces were categorized on the individual
      level. 

PMID- 24890396
TI  - Transcript suppression of TaGW2 increased grain width and weight in bread wheat.
AB  - Bread wheat (Triticum aestivum L.) is a major staple crop in the world. Grain
      weight is a major factor of grain yield in wheat, and the identification of
      candidate genes associated with grain weight is very important for high-yield
      breeding of wheat. TaGW2 is an orthologous gene of rice OsGW2 that negatively
      regulates the grain width and weight in rice. There are three TaGW2 homoeologs in
      bread wheat, TaGW2A, TaGW2B, and TaGW2D. In this study, a specific TaGW2-RNA
      interference (RNAi) cassette was constructed and transformed into a Chinese bread
      wheat variety 'Shi 4185' with small grain. The transcript levels of TaGW2A,
      TaGW2B, and TaGW2D were simultaneously downregulated in TaGW2-RNAi transgenic
      wheat lines. Compared with the controls, TaGW2-underexpressing transgenic lines
      displayed significantly increases in the grain width and weight, suggesting that
      TaGW2 negatively regulated the grain width and weight in bread wheat. Further
      transcript analysis showed that in different bread wheat accessions, the
      transcript abundance of TaGW2A was negatively associated with the grain width. 

PMID- 24890398
TI  - Childhood maltreatment and educational outcomes: evidence from South Africa.
AB  - Many South African children experience maltreatment, but we know little about the
      effects on long-term child development. Using the only representative dataset
      that includes a module on childhood maltreatment for a metropolitan city in South
      Africa, we explore the association between different measures of childhood
      maltreatment and two educational outcomes (numeracy test scores and dropout). Our
      study provides an estimate of the association between childhood maltreatment and
      educational outcomes in a developing country where maltreatment is high. We
      control for potential confounders using a range of statistical techniques and add
      several robustness checks to evaluate the strength of our findings. Our results
      indicate that children who are maltreated suffer large adverse consequences in
      terms of their numeracy test scores and probability of dropout and that the
      estimated effects of maltreatment are larger and more consistent for the most
      severe type of maltreatment.

PMID- 24890397
TI  - Upregulation of transcripts for metabolism in diverse environments is a shared
      response associated with survival and adaptation of Klebsiella pneumoniae in
      response to temperature extremes.
AB  - Klebsiella pneumoniae being ubiquitous in nature encounters wide differences in
      environmental condition. The organism's abundance in natural water reservoirs
      exposed to temperature variation forms the basis of its persistence and spread in
      the soil and other farm produce. In order to investigate the effect of
      temperature changes on the survival and adaptation of the bacteria, the
      transcriptional response of K. pneumoniae subjected to low (20  degrees C) and
      high (50  degrees C) temperature shock were executed using Applied Biosystems
      SOLiD platform. Approximately, 33 and 34% of protein coding genes expressed in
      response to 20 and 50  degrees C, respectively, displayed significant up- or
      downregulation (p < 0.01). Most of the significantly expressed transcripts mapped
      to metabolism, membrane transport, and cell motility were downregulated at 50 
      degrees C, except for protein folding, sorting, and degradation, suggesting that
      heat stress causes general downregulation of gene expression together with
      induction of heat shock proteins. While at 20  degrees C, the transcripts of
      carbohydrate, lipid, and amino acid metabolism were highly upregulated.
      Hypothetical proteins as well as canonical heat and cold shock proteins, viz.
      grpE, clpX, recA, and deaD were upregulated commonly in response to 20 and 50 
      degrees C. Significant upregulation of genes encoding ribosomal proteins at 20
      and 50  degrees C possibly suggest their role in the survival of K. pneumoniae
      cells under low- and high-temperature stress.

PMID- 24890395
TI  - Targeting mucus hypersecretion: new therapeutic opportunities for COPD?
AB  - Airway mucus has a key role in protective innate immune responses, but excessive
      mucus production and secretion in proximal and in distal airways are associated
      with disabling symptoms (cough and sputum), lung function decline, exacerbations
      and mortality in patients with chronic obstructive pulmonary disease (COPD).
      Cellular and molecular mechanisms leading to mucin production and secretion have
      largely been identified using cultured epithelial cells and animal models.
      Cigarette smoke and microbial products are potent triggers of mucin production,
      which involves recognition of specific molecular patterns by cognate receptors
      and activation of metalloproteases at the epithelial cell surface, leading to
      epidermal growth factor receptor activation and mucin mRNA and protein synthesis.
      After mucin synthesis has occurred, mucins are tightly packed into
      intracytoplasmic granules. Many stimuli induce secretion of mucin granules from
      epithelial cells, but neutrophil serine proteases are the most potent inducers of
      mucin secretion. Neutrophils recruited to the airway epithelium also promote
      mucin production via neutrophil proteases and oxidative stress. Several drugs
      currently available for the treatment of COPD patients reduced mucus
      hypersecretion in preclinical models relevant to COPD, but their effects on mucus
      hypersecretion in humans have not been assessed. Testing the effects of these
      drugs and of novel molecules designed for reducing mucus production and/or
      secretion will require performing specifically designed clinical trials. These
      trials will be necessary to explore the hypothesis that reducing mucus
      hypersecretion is beneficial in COPD patients. 

PMID- 24890399
TI  - Beneficial properties of natural phenols: highlight on protection against
      pathological conditions associated with amyloid aggregation.
AB  - Mediterranean and Asian diets are currently considered as the most healthy
      traditional feeding habits effective against risk of age-associated, particularly
      cardiovascular and neurodegenerative, diseases. A common feature of these two
      regimens is the abundance of foods and beverages of plant origin (green tea,
      extra virgin olive oil, red wine, spices, berries, and aromatic herbs) that are
      considered responsible for the observed beneficial effects. Epidemiological data
      suggest that the phenolic component remarkably enriched in these foods plays an
      important role in reducing the incidence of amyloid diseases, pathological
      conditions associated to tissue deposition of toxic protein aggregates
      responsible for progressive functional deterioration. Great effort is being spent
      to provide knowledge on the effects of several natural phenols in this context,
      moving from the test tube to animal models and, more slowly, to the patient's
      bed. An emerging feature that makes these molecules increasingly attractive for
      amyloid disease prevention and therapy is their wide spectrum of activity: recent
      pieces of evidence suggest that they can inhibit the production of amyloidogenic
      peptides from precursors, increase antioxidant enzyme activity, activate
      autophagy and reduce inflammation. Our concept should than shift from considering
      natural phenols simply as antioxidants or, at the best, as amyloid aggregation
      inhibitors, to describing them as potentially multitargeting drugs. A main
      concern is the low bioavailability of such compounds and efforts aimed at
      improving it are underway, with encapsulation strategies being the most promising
      ones.

PMID- 24890400
TI  - Role of perceived stress in the occurrence of preterm labor and preterm birth
      among urban women.
AB  - INTRODUCTION: This study examined whether prenatal perceived stress levels during
      pregnancy were associated with preterm labor or preterm birth. METHODS: Perceived
      stress levels were measured at 16 weeks' gestation or less and between 20 and 24
      weeks' gestation in a sample of 1069 low-income pregnant women attending Temple
      University prenatal care clinics. Scores were averaged to create a single measure
      of prenatal stress. Preterm birth was defined as the occurrence of a spontaneous
      birth prior to 37 weeks' gestation. Preterm labor was defined as the occurrence
      of regular contractions between 20 and 37 weeks' gestation that were associated
      with changes in the cervix. RESULTS: Independent of potential confounding
      factors, prenatal perceived stress was not associated with preterm labor (odds
      ratio [OR], 1.10; 95% confidence interval [CI], 0.69-1.78; P = .66); however,
      prenatal stress trended toward an association with preterm birth (OR, 1.49; 95%
      CI, 1.00-2.23; P = .05). The strongest predictor of preterm labor was a history
      of preterm labor in a prior pregnancy. Women with a history of preterm labor were
      2 times more likely to experience preterm labor in the current pregnancy than
      women who did not have a preterm labor history (OR, 2.16; 95% CI, 1.05-4.41; P =
      .04). Historical risk factors for preterm birth, such as African American race, a
      history of abortion, or a history of preterm birth, were not related to preterm
      labor. The strongest predictor of preterm birth was having a history of preterm
      birth in a prior pregnancy (OR, 2.55; 95% CI, 1.54-4.24; P < .001). DISCUSSION:
      Prenatal perceived stress levels may be a risk factor for preterm birth
      independent of preterm labor; however, prenatal stress was not associated with
      preterm labor. Risk factors for preterm labor may be different from those of
      preterm birth.

PMID- 24890402
TI  - Robert John Wootton (1942-2014).

PMID- 24890401
TI  - Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in
      gestational hypertension.
AB  - OBJECTIVE: To compare functional characteristics of maternal thoraco-abdominal
      arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy.
      METHODS: This retrospective study included women with singleton pregnancies
      during the third trimester, which were either uncomplicated or complicated with
      different clinical types of hypertension: non-proteinuric gestational
      hypertension (GH), early-onset pre-eclampsia (PE) diagnosed < 34 weeks or late
      onset PE diagnosed >= 34 weeks. Demographic maternal and neonatal data were
      recorded, together with maternal serum and urine analytes. All women underwent
      standardized automated blood-pressure measurement, together with non-invasive
      impedance cardiography (ICG), for measurement of cardiac output (CO), aortic flow
      velocity index (VI) and aortic flow acceleration index (ACI). A standardized
      combined Doppler-electrocardiography assessment of maternal venous hemodynamics
      was performed to measure renal interlobar vein impedance index (RIVI), hepatic
      vein impedance index (HVI) and venous pulse transit time (VPTT) in liver and
      kidneys. Finally, resistance index (RI), pulsatility index (PI) and arterial
      pulse transit time (APTT) were measured in the uterine arcuate arteries. Mann
      Whitney U-tests and Fisher's exact tests were used for intergroup comparisons,
      and linear dependence between variables was assessed using Pearson's correlation
      coefficient (r). RESULTS: A total of 150 pregnancies were evaluated: 22 with
      uncomplicated pregnancy, 41 GH, 31 early PE and 56 late PE. Aortic VI and ACI
      were lower in GH, early PE and late PE than in uncomplicated pregnancy. Both
      early PE and late PE differed from GH by having shorter APTT in the uterine
      arcuate arteries and higher RIVI. Hemodynamic abnormalities were most pronounced
      in early PE, during which uterine arcuate artery RI was higher and VPTT in
      kidneys was shorter than in late PE. There was a significant correlation between
      degree of proteinuria and RIVI for the left (r = 0.381) and right (r = 0.347)
      kidney in late PE, but this was not true for early PE. CONCLUSIONS: There is a
      gradient of worsening arterial and venous hemodynamic abnormalities from GH to
      late PE and then to early PE. Venous hemodynamic abnormalities are present only
      in PE, with a linear correlation between proteinuria and RIVI in late PE. The
      role of the maternal venous compartment in the pathophysiology and etiology of PE
      related symptoms may be much more important than considered at present.

PMID- 24890403
TI  - Effects of dietary lipid levels on mitochondrial gene expression in low and high
      feed efficient families of rainbow trout Oncorhynchus mykiss.
AB  - A 2 * 3 factorial study was conducted to evaluate the effects of dietary lipid
      level on mitochondrial gene expression in mixed sex rainbow trout Oncorhynchus
      mykiss. Practical diets with a fixed crude protein content of 42%, formulated to
      contain 10% (42/10), 20% (42/20) and 30% (42/30) dietary lipid, were fed to
      triplicate groups of either low-feed efficient (F129; mean +/- s.d. = 105.67 +/-
      3.04 g initial average mass) or high-feed efficient (F134; mean +/- s.d. = 97.86
      +/- 4.02 g) families of fish, to apparent satiety, twice per day, for 108 days.
      At the end of the experiment, diets 42/20 and 42/30 led to similar fish condition
      factors, which were higher than that observed with diet 42/10 (P < 0.05). F134
      fish fed diet 42/10 showed the highest hepato-somatic index, while there was no
      significant difference among all the other treatments (P < 0.05). When the group
      of F134 fish fed diet 42/10 was used as the calibrator for gene expression
      analysis, the five genes selected for their involvement in lipid metabolism
      (complex I-nd1, complex III-cytb, complex IV-cox1, complex IV-cox2 and complex V
      atp6) were up-regulated in the muscle and down-regulated in both the liver and
      the intestine. There was a significant family * diet interaction regarding nd1,
      cox2 and atp6 in the liver; nd1, cytb, cox1, cox2 and atp6 in the intestine, and
      nd1, cytb, cox1, cox2 and atp6 in the muscle (P < 0.05). The overall results of
      this study constitute basic information for the understanding of molecular
      mechanisms of lipid metabolism at the mitochondrial level in fishes.

PMID- 24890404
TI  - Neurobehavioural analysis of developmental iron deficiency in Oreochromis aureus
      * Oreochromis niloticus.
AB  - The objective of this study was to examine the association between brain iron
      measurements of monoamine function and behavioural measurements of learning and
      memory. Male hybrid tilapias Oreochromis aureus * Oreochromis niloticus were fed
      either an iron-deficient (ID) diet or an iron-adequate (IA) diet for 8 weeks. The
      ID fishes showed significantly lower iron content in brain and decreasing
      learning and memory capacity. The fishes that showed increased learning and
      memory capacity had higher levels of iron and monoamine oxidase activity in
      brain. In addition, the results showed that learning and memory behaviours were
      related to monoamine (dopamine and noradrenaline) concentration in the brain.
      This suggests that iron can enhance learning and memory capacity in fishes and
      that the effect may have monoaminergic mediation in discrimination learning and
      memory tasks. The experimental data suggest that the properties and neural basis
      of learning and memory of teleosts are notably similar to those of land
      vertebrates.

PMID- 24890405
TI  - Gender distribution, sexual size dimorphism and morphometric sexing in ballan
      wrasse Labrus bergylta.
AB  - In wild ballan wrasse Labrus bergylta, mass-length relationships were not
      different between genders, and positive allometry was found in the mixed-gender
      population. Male-biased sexual size dimorphism was significant and the most
      effective morphometric method for sexing L. bergylta outside of the species
      spawning window used body mass (M(B) in g), total body length (L(T) in mm) and
      Fulton's condition factor (K) as discriminant variables to predict gender with
      91% accuracy. The discriminant score (S(D)) of a specimen can be calculated as
      S(D)  = 0.01 M(B)- 0.016 L(T)- 3.835 K + 6.252 to predict its gender as female or
      male if S(D) is < 1.459 or S(D) is > 1.504, respectively. There was a potential
      trend towards earlier sexual inversion compared to previous studies at comparable
      latitudes. Sex change is a phenotypically plastic trait under social control in
      haremic fishes and should be monitored in increasingly exploited L. bergylta.

PMID- 24890406
TI  - The influence of brood loss on nest abandonment decisions in largemouth bass
      Micropterus salmoides.
AB  - Largemouth bass Micropterus salmoides broods were experimentally reduced in size
      to test whether brood size (BS) and simulated brood depredation affect the
      decision by a male to continue providing care for its brood or to abandon that
      brood prematurely before its offspring reach independence. The highest ranked of
      the generalized linear models predicting brood abandonment was based on the
      number of offspring remaining in a nest following brood devaluation, indicating
      that parental male fish reassess the value of a brood following perturbation.
      Paternal M. salmoides were more likely to abandon their broods if initial BS was
      small before devaluation, and if there was a greater decrease in BS, indicating a
      threshold for both the amount of brood loss and remaining BS. Larger, older males
      were also less likely to abandon their brood than smaller, younger conspecifics.
      These results have broad implications for determining drivers of parental care
      trade-offs and how individuals assess the value of a brood. 

PMID- 24890407
TI  - Direct ageing of Thunnus thynnus from the eastern Atlantic Ocean and western
      Mediterranean Sea using dorsal fin spines.
AB  - This study deals with important methodology issues that affect age estimates of
      eastern Atlantic bluefin tuna Thunnus thynnus using dorsal fin spines. Nearly
      3800 spine sections were used from fish caught in the north-east Atlantic Ocean
      and western Mediterranean Sea over a 21 year period. Edge type and marginal
      increment analyses indicated a yearly periodicity of annulus formation with the
      translucent bands (50% of occurrence) appearing from October to May. Nucleus
      vascularization seriously affected specimens older than 6 years, with the
      disappearance of 40-50% of the presumed annuli by that age. An alternate
      sectioning location was a clear improvement and this finding is an important
      contribution to the methodology of using this structure for ageing the full
      length range of eastern T. thynnus. Finally, there were no significant
      differences between the coefficients of von Bertalanffy growth model estimated
      from mean length at age data (Linfinity  = 327.4; k = 0.097; t0  = -0.838) and
      those estimated from the growth curves accepted for the eastern and western T.
      thynnus management units.

PMID- 24890408
TI  - Distinction among North Atlantic cod Gadus morhua stocks by tissue fatty acid
      profiles.
AB  - The fatty acid (FA) profiles of the white muscle and heart tissues of cod Gadus
      morhua from five locations, Faroe Bank, Faroe Plateau, North-West Iceland, Norway
      Barents Sea and Denmark-Skagerrak, were population dependent. The interregional
      differences of FAs were significantly dissimilar (P < 0.01) in most cases. By way
      of a rapid and simple analytical method, the stock dependence and harvest
      location of individual G. morhua were chemometrically determined by multivariate
      principal component analysis. The difference among the stocks was correlated with
      the average water temperature at the harvest locations. It thus appears that the
      tissue FA profile is a phenotypic trait that is partly temperature driven.

PMID- 24890409
TI  - Precision of the age-length increments of three cyprinids: effects of fish number
      and sub-sampling strategy.
AB  - The effects of number of fish that are aged and scale sub-sampling strategies on
      the precision of estimates of mean age-length increments from populations of
      Rutilus rutilus, Leuciscus leuciscus and Leuciscus cephalus were tested. Analyses
      used data derived from river fish communities in eastern England, U.K.. Regarding
      the number of fishes analysed in each age group, for each species and mean fork
      length increment at age, significant relationships were detected between sample
      size (n) and the coefficient of variation of the mean (Z) and mean length
      increment x? and measured variance (s(2)). This enabled calculation of the number
      of scales for producing a mean length increment at age according to n=ax?(b(
      2))Zx?(-2). Outputs indicated that the number of scales requiring ageing
      increased substantially as precision increased, but with little variation between
      species per age category. Ageing between seven and 12 scales per age group would
      thus provide estimates at 10% precision. As the ages of fishes are not known in
      advance of scale ageing, the effect of scale sub-sampling regime on precision was
      also tested using randomized strategies of 10 fish per 5 mm, five per 5 mm, three
      per 5 mm, 10 per 10 mm, five per 10 mm and three per 10 mm. These were applied to
      the datasets and the consequences of their reduction in the number of scales for
      precision were determined using Z=a(0.5)x?((b/2)(-1))n(-0.5). When compared to no
      sub-sampling, three per 10 mm always significantly reduced data precision,
      whereas 10 per 5 mm never significantly reduced precision. These outputs can thus
      be applied to the design of fish sampling protocols where age and growth
      estimates are required, with the randomized sub-sampling likely to be the most
      useful strategy.

PMID- 24890410
TI  - Life-history traits of temperate and thermophilic barracudas (Teleostei:
      Sphyraenidae) in the context of sea warming in the Mediterranean Sea.
AB  - This study indicated that the life-history traits of European barracuda Sphyraena
      sphyraena are apparently better suited to their environmental conditions compared
      to the more physically restricted life-history traits of the yellow-mouth
      barracuda Sphyraena viridensis, which co-habit the north-western Mediterranean
      Sea. The latter thermophilic species has a considerably higher reproductive
      potential as it invests its energy reserves in larger numbers of hydrated eggs
      per spawning batch. This would favour its population growth rates within the
      study area, especially if sea warming continues, in which case it is likely that
      the spawning phenology of this species would give it an advantage. 

PMID- 24890411
TI  - Observations of growth and postspawning survival of lumpfish Cyclopterus lumpus
      from mark-recapture studies.
AB  - Growth and postspawning survival of lumpfish Cyclopterus lumpus are described by
      mark-recapture experiments using juveniles in offshore areas in the north-east
      Atlantic Ocean and spawning adults in coastal Norway and Iceland. A female fish
      tagged as a juvenile and recaptured as an adult matured in a period of 18 months,
      providing the first observation on development in a wild C. lumpus. The von
      Bertalanffy growth function, fitted to data from recaptured fish, was used to
      estimate K and Linfinity and recaptured fish spawning after a year at liberty
      indicated a postspawning survival of c. 10% in Iceland. 

PMID- 24890412
TI  - In memoriam. Roger E. Marchant, 8 March 1951-31 January 2014.

PMID- 24890413
TI  - Gait training early after stroke with a new exoskeleton--the hybrid assistive
      limb: a study of safety and feasibility.
AB  - BACKGROUND: Intensive task specific training early after stroke may enhance
      beneficial neuroplasticity and functional recovery. Impaired gait after
      hemiparetic stroke remains a challenge that may be approached early after stroke
      by use of novel technology. The aim of the study was to investigate the safety
      and feasibility of the exoskeleton Hybrid Assistive Limb (HAL) for intensive gait
      training as part of a regular inpatient rehabilitation program for hemiparetic
      patients with severely impaired gait early after stroke. METHODS: Eligible were
      patients until 7 weeks after hemiparetic stroke. Training with HAL was performed
      5 days per week by the autonomous and/or the voluntary control mode offered by
      the system. The study protocol covered safety and feasibility issues and aspects
      on motor function, gait performance according to the 10 Meter Walking Test
      (10MWT) and Functional Ambulation Categories (FAC), and activity performance.
      RESULTS: Eight patients completed the study. Median time from stroke to inclusion
      was 35 days (range 6 to 46). Training started by use of the autonomous HAL mode
      in all and later switched to the voluntary mode in all but one and required one
      or two physiotherapists. Number of training sessions ranged from 6 to 31 (median
      17) and walking time per session was around 25 minutes. The training was well
      tolerated and no serious adverse events occurred. All patients improved their
      walking ability during the training period, as reflected by the 10MWT (from 111.5
      to 40 seconds in median) and the FAC (from 0 to 1.5 score in median).
      CONCLUSIONS: The HAL system enables intensive training of gait in hemiparetic
      patients with severely impaired gait function early after stroke. The system is
      safe when used as part of an inpatient rehabilitation program for these patients
      by experienced physiotherapists.

PMID- 24890415
TI  - BMP signaling participates in late phase differentiation of the retina, partly
      via upregulation of Hey2.
AB  - Bone morphogenetic protein (BMP) plays pivotal roles in early retinal
      development. However, its roles in the late phase of retinal development remain
      unclear. We found that BMP receptors and ligands were expressed in the postnatal
      mouse retina. Furthermore, immunostaining revealed that phosphorylated Smads were
      enriched in various cells types in the inner nuclear layer postnatally. However,
      phosphorylated Smads were not detected in photoreceptors, suggesting that BMP may
      play roles in retinal cells in the inner nuclear layer. Forced expression of
      constitutively active BMP receptors during retinal development resulted in an
      increased number of bipolar cells and Muller glia and a decreased number of rod
      photoreceptors; however, proliferation was not perturbed. The expression of
      dominant negative BMP receptors resulted in a decreased number of Muller glia and
      bipolar cells. In addition, inhibiting BMP signaling in retinal monolayer
      cultures abrogated Muller glial process extension, suggesting that BMP signaling
      also plays a role in the maturation of Muller glia. The expression of the basic
      helix-loop-helix transcription factor Hey2 was induced by BMP signaling in
      retinas. The coexpression of sh-Hey2 with constitutively active BMP receptors
      suggested that the effects of BMP signaling on retinal differentiation could be
      attributed partly to the induction of Hey2 by BMP. We propose that BMP signaling
      plays pivotal roles in the differentiation of retinal progenitor cells into late
      differentiating retinal cell types and in the maturation of Muller glia; these
      effects were mediated, at least in part, by Hey2.

PMID- 24890416
TI  - A risk index for advanced neoplasia on the second surveillance colonoscopy in
      patients with previous adenomatous polyps.
AB  - BACKGROUND: Predicting the risk of advanced colorectal neoplasia on the second
      surveillance colonoscopy could help tailor surveillance. OBJECTIVE: To derive and
      validate a risk index for advanced neoplasia on the second surveillance
      colonoscopy. DESIGN: Retrospective cohort. SETTING: Single-specialty practice;
      Veterans Affairs Medical Center. PATIENTS: A total of 965 patients with baseline
      adenomatous polyps, 2 surveillance colonoscopies, and no reported family history
      of colorectal cancer; validation cohort of 372. INTERVENTIONS: Multivariable
      logistic regression including demographics and previous colonoscopy results;
      derivation and validation of a risk index. MAIN OUTCOME MEASUREMENTS: Advanced
      adenoma (>=1 cm in size, villous histology, or high-grade dysplasia) on the
      second surveillance colonoscopy. RESULTS: Mean age was 57.8 +/- 9.8 years, 62%
      were men, and 36% had an advanced adenoma on the index colonoscopy. Associated
      with advanced adenoma on the second surveillance colonoscopy were age at index
      colonoscopy (scored 0 for younger than 55 years of age, 1 for 55-59 years of age,
      2 for 60-64 years of age, and 3 for older than 65 years of age) and previous
      findings (non-neoplastic, nonadvanced, advanced [scored 0, 1, and 2,
      respectively]) on index colonoscopy and the first surveillance colonoscopy, with
      scores ranging from 1 to 7. Risks of advanced adenoma on the second surveillance
      colonoscopy with scores of 5 or less and more than 5 were 4.8% (95% confidence
      interval, 3.5%-6.4%) and 14.9% (95% confidence interval, 7.4%-25.7%),
      respectively, comprising 93% and 7%, respectively, of the cohort. Corresponding
      results in the validation cohort were 5.6% and 19.2%, respectively, comprising
      86.1% and 13.9%, respectively, of the cohort. LIMITATIONS: Retrospective study
      with potential for selection bias. CONCLUSION: This index stratifies the risk of
      advanced adenoma on the second surveillance colonoscopy. If validated
      independently, it may be useful for tailoring surveillance.

PMID- 24890414
TI  - The Treponema denticola AtcR LytTR domain-containing response regulator interacts
      with three architecturally distinct promoter elements: implications for
      understanding the molecular signaling mechanisms that drive the progression of
      periodontal disease.
AB  - Treponema denticola is an oral spirochete and periopathogen that transitions from
      low abundance in healthy subgingival crevices to high abundance in periodontal
      pockets. The T. denticola response regulator AtcR harbors the relatively rare,
      LytTR DNA-binding domain. LytTR domain containing response regulators control
      critical transcriptional responses required for environmental adaptation. Using a
      multi-step bioinformatics approach, 26 strong lytTR recognition motifs were
      identified in the genome of T. denticola strain 35405. Electrophoretic mobility
      shift assays demonstrated that AtcR binds to these recognition motifs. High
      specificity-high affinity complexes formed with phosphorylated AtcR. The LytTR
      recognition sequences were found to exist in three distinct promoter
      architectures designated as LytTR1, LytTR2 and LytTR3 promoters. LytTR1 and
      LytTR2 promoters harbor sigma(54) binding sites. The functional diversity of the
      proteins encoded by the putative AtcR regulon suggests that AtcR sits at the top
      of a regulatory cascade that plays a central role in facilitating T. denticola's
      ability to adapt to changing environmental conditions and thrive in periodontal
      pockets.

PMID- 24890417
TI  - Use of side-viewing endoscope to treat a bleeding duodenal diverticulum.

PMID- 24890418
TI  - EUS-guided, through-the-needle forceps biopsy: a novel tissue acquisition
      technique.

PMID- 24890419
TI  - Transenteric anastomosis with lumen-apposing metal stent as a conduit for
      iterative endotherapy of malignant biliary obstruction in altered anatomy.

PMID- 24890420
TI  - A case of hereditary hemorrhagic telangiectasia with repeated hemobilia arrested
      by argon plasma coagulation under direct peroral cholangioscopy.

PMID- 24890421
TI  - Ethanol lavage of huge hepatic cysts by using EUS guidance and a percutaneous
      approach.
AB  - BACKGROUND: EUS-guided and percutaneous lavage therapy for large hepatic cysts
      can replace surgical drainage. EUS-guided therapy can especially enable the
      alcohol lavage to be done with a 1-step approach. OBJECTIVE: To evaluate the
      utility of EUS-guidance and percutaneous ethanol lavage therapy. DESIGN:
      Retrospective cohort study. SETTING: Tertiary-care referral teaching hospital.
      PATIENTS: Adult patients with large liver cysts who underwent cyst drainage and
      alcohol ablation between 2009 and 2012. INTERVENTIONS: Ethanol lavage via
      percutaneous and/or EUS-guided approaches. MAIN OUTCOME MEASUREMENTS:
      Feasibility, efficacy, and safety of ethanol lavage. RESULTS: Seventeen patients
      with 19 hepatic cysts were enrolled. The median cyst volume before therapy was
      368.9 mL (interquartile range, 195.3-795.9 mL). Ten cysts were drained by the
      percutaneous approach with a pigtail catheter, and 8 cysts underwent EUS-guided
      aspiration and lavage treatment. In 1 case, both the percutaneous approach and
      EUS-guided puncture were used. During the median 11.5-month follow-up of the
      percutaneous approach group, the cysts showed 97.5% reduction. During the median
      15-month follow-up of the EUS-guided group, the cysts showed nearly 100%
      reduction. Percutaneous catheter drainage ethanol lavage was more feasible for
      right-sided larger cysts, whereas the EUS-guided approach was useful for left
      sided lobe cysts. LIMITATIONS: Single-center retrospective study. CONCLUSION:
      Excellent symptomatic and radiologic responses and long-term results were
      achieved with percutaneous catheter-guided and EUS-guided ethanol lavage. Ethanol
      lavage could be considered a primary method of treatment for hepatic cysts given
      its high degree of technical feasibility and safety.

PMID- 24890423
TI  - Salvage posterior peroral endoscopic myotomy.

PMID- 24890424
TI  - Tamponade of a bleeding pseudocyst with a fully covered metal stent.

PMID- 24890422
TI  - High and low negative pressure suction techniques in EUS-guided fine-needle
      tissue acquisition by using 25-gauge needles: a multicenter, prospective,
      randomized, controlled trial.
AB  - BACKGROUND: EUS-guided FNA (EUS-FNA) has a high diagnostic accuracy for
      pancreatic diseases. However, although most reports have typically focused on
      cytology, histological tissue quality has rarely been investigated. The
      effectiveness of EUS-FNA combined with high negative pressure (HNP) suction was
      recently indicated for tissue acquisition, but has not thus far been tested in a
      prospective, randomized clinical trial. OBJECTIVE: To evaluate the adequacy of
      EUS-FNA with HNP for the histological diagnosis of pancreatic lesions by using 25
      gauge needles. DESIGN: Prospective, single-blind, randomized, controlled
      crossover trial. SETTING: Seven tertiary referral centers. PATIENTS: Patients
      referred for EUS-FNA of pancreatic solid lesions. From July 2011 to April 2012,
      90 patients underwent EUS-FNA of pancreatic solid masses by using normal negative
      pressure (NNP) and HNP with 2 respective passes. The order of the passes was
      randomized, and the sample adequacy, quality, and histology were evaluated by a
      single expert pathologist. INTERVENTION: EUS-FNA by using NNP and HNP. MAIN
      OUTCOME MEASUREMENTS: The adequacy of tissue acquisition and the accuracy of
      histological diagnoses made by using the EUS-FNA technique with HNP. RESULTS: We
      found that 72.2% (65/90) and 90% (81/90) of the specimens obtained using NNP and
      HNP, respectively, were adequate for histological diagnosis (P = .0003, McNemar
      test). For 73.3% (66/90) and 82.2% (74/90) of the specimens obtained by using NNP
      and HNP, respectively, an accurate diagnosis was achieved (P = .06, McNemar
      test). Pancreatitis developed in 1 patient after this procedure, which subsided
      with conservative therapy. LIMITATIONS: This was a single-blinded, crossover
      study. CONCLUSION: Biopsy procedures that combine the EUS-FNA with HNP techniques
      are superior to EUS-FNA with NNP procedures for tissue acquisition. ( CLINICAL
      TRIAL REGISTRATION NUMBER: UMIN000005939.).

PMID- 24890425
TI  - Sessile serrated adenomas/polyps with cytologic dysplasia: a triple threat for
      interval cancer.

PMID- 24890426
TI  - Application of endoscopic hemostatic forceps for uterine cervical bleeding.

PMID- 24890427
TI  - Duodenal stent placement for duodenal obstruction caused by pancreatic cancer
      associated with annular pancreas.

PMID- 24890428
TI  - Endoscopic necrosectomy by using a transgastric fully covered esophageal metal
      stent.

PMID- 24890429
TI  - Methane emissions from Amazonian Rivers and their contribution to the global
      methane budget.
AB  - Methane (CH4 ) fluxes from world rivers are still poorly constrained, with
      measurements restricted mainly to temperate climates. Additional river flux
      measurements, including spatio-temporal studies, are important to refine
      extrapolations. Here we assess the spatio-temporal variability of CH4 fluxes from
      the Amazon and its main tributaries, the Negro, Solimoes, Madeira, Tapajos,
      Xingu, and Para Rivers, based on direct measurements using floating chambers.
      Sixteen of 34 sites were measured during low and high water seasons. Significant
      differences were observed within sites in the same river and among different
      rivers, types of rivers, and seasons. Ebullition contributed to more than 50% of
      total emissions for some rivers. Considering only river channels, our data
      indicate that large rivers in the Amazon Basin release between 0.40 and 0.58 Tg
      CH4  yr(-1) . Thus, our estimates of CH4 flux from all tropical rivers and rivers
      globally were, respectively, 19-51% to 31-84% higher than previous estimates,
      with large rivers of the Amazon accounting for 22-28% of global river CH4
      emissions. 

PMID- 24890430
TI  - A retrospective and geographical epidemiological survey of traumatic myiasis in
      southern Italy.
AB  - A survey on the prevalence and geographical distribution of traumatic myiasis in
      sheep, and the risk factors for the disease, was carried out in a region of
      southern Italy. A total of 138 sheep flocks were selected and visited to acquire
      data on the presence or absence of traumatic myiasis using both a questionnaire
      for retrospective analysis and animal inspection. Prevalences registered at the
      farm and animal levels, respectively, were 8.7% and 6.3% in 2010, and 5.8% and
      5.0% in 2011. Records of the occurrence of the parasitic disease in this region
      are recent: a statistically significant (P < 0.01) progressive increase in the
      number of farms affected (from 0.7% to 8.7%) has been registered since 2007.
      Wohlfahrtiosis was found in 11 of 95 (11.6%) geographical units sampled and three
      significant (P < 0.05) clusters of spatial farm aggregation were identified in
      the southern part of the study area. A total of 158 presently uninfested farms
      were considered to be at high risk for transmission as a result of their
      proximity to infested farms. The spreading of Wohlfahrtia magnifica (Diptera:
      Sarcophagidae) in southern regions of Italy represents a warning that the risk
      for infestation may become more significant in other Italian regions, as well as
      other European countries. 

PMID- 24890431
TI  - Improving site-directed RNA editing in vitro and in cell culture by chemical
      modification of the guideRNA.
AB  - Adenosine-to-inosine deamination can be re-addressed to user-defined mRNAs by
      applying phosphothioate/2'-methoxy-modified guideRNAs. Dense chemical
      modification of the guideRNA clearly improves performance of the covalent
      conjugates inside the living cell. Furthermore, careful positioning of a few
      modifications controls editing selectivity in vitro and was exploited for the
      challenging repair of the Factor 5 Leiden missense mutation. 

PMID- 24890434
TI  - Improving surface and transport properties of macroporous hydrogels for bone
      regeneration.
AB  - Hydrogels have been frequently considered as suitable materials for hard tissue
      engineering as mineralized extracellular matrix analogue. However, major lacks in
      bone-substitution still concern the mimicking of native microenvironment for
      promoting cell differentiation into osteogenic way. Here, we propose the study of
      mineralized macroporous hydrogels (mMHs) made of poly(ethylenglycol)diacrylate
      fabricated by the combination of ultraviolet photopolymerization/salt leaching
      technique and treated by osteopromotive medium. We demonstrate that peculiar
      morphological and chemical features of mMH are crucial to create a reservoir
      system able to efficiently recruit environmental signals to cells. In particular,
      mass transport mechanisms are regulated by the coupling of a Knudsen-type
      diffusion within the void space of the pores with a standard diffusion mechanism
      through the pores walls. Meanwhile, the deposition of hydrophilic mineral phases
      onto the pore surface further affects transport mechanisms, in view of their
      capability to establish interactions with water molecules and to exert mechanical
      constrains on the swelling of the hydrogel network, thus promoting slower
      diffusion kinetics. These properties concur to influence in vitro human
      mesenchymal stem cells activities: macropore architecture of the hydrogel-like
      network positively affects cell recognition as compared to nonporous scaffolds,
      while osteopromotive treatment mainly allows to guide differentiation in
      osteogenic way as proved by staining of in vitro formed Ca-rich mineral deposits
      (i.e., alizarin red) and expression via reverse transcription-polymerase chain
      reaction of main bone markers. Hence, mMH is promising to develop three
      dimensional scaffolds as experimental model to study in vitro cell events during
      bone regeneration.

PMID- 24890435
TI  - Job satisfaction and turnover intention among Jordanian nurses in psychiatric
      units.
AB  - Psychiatric nursing has been identified as a stressful occupation, and this
      stress could affect individuals' health, well-being, and job satisfaction. The
      stress of nurses might also affect the organization in terms of absenteeism and
      quality of care. The purpose of this study was to examine the relationship
      between job satisfaction and turnover intention among Jordanian nurses in the
      psychiatric units of the Jordanian National Mental Health Center. A descriptive,
      correlational, cross-sectional design was used. Nurses were asked to complete a
      demographic data sheet and questionnaires regarding job satisfaction and turnover
      intention. Of the 179 questionnaires distributed, 154 were completed, with an 86%
      response rate. The results revealed a statistically-significant negative
      relationship between job satisfaction and turnover intention. The findings of the
      study are consistent with previous research regarding the negative relationship
      between job satisfaction and turnover intention. The findings provide new
      information about Jordanian nurses who work in government hospital psychiatric
      services. 

PMID- 24890436
TI  - UV exposure inhibits intestinal tumor growth and progression to malignancy in
      intestine-specific Apc mutant mice kept on low vitamin D diet.
AB  - Mortality from colorectal cancer increases with latitude and decreases with
      ambient UV radiation. We investigated whether moderate UV dosages could inhibit
      intestinal tumor development and whether this corresponded with UV-induced
      vitamin D. FabplCre;Apc(15lox/+) mice, which develop intestinal tumors, and their
      parents were put on a vitamin D-deficient diet. Next to a control group, one
      group was vitamin D supplemented and another one group was daily UV irradiated
      from 6 weeks of age. Vitamin D statuses after 6 weeks of treatment were markedly
      increased: mean +/- SD from 7.7 +/- 1.9 in controls to 75 +/- 15 nmol/l with
      vitamin D supplementation (no gender difference), and to 31 +/- 13 nmol/l in
      males and 85 +/- 17 nmol/l in females upon UV irradiation. The tumor load (area
      covered by tumors) at 7.5 months of age was significantly reduced in both the
      vitamin D-supplemented group (130 +/- 25 mm(2), p = 0.018) and the UV-exposed
      group (88 +/- 9 mm(2), p < 0.0005; no gender differences) compared to the control
      group (202 +/- 23 mm(2)). No reductions in tumor numbers were found. Only UV
      exposure appeared to reduce progression to malignancy (p = 0.014). Our
      experiments clearly demonstrate for the first time an inhibitory effect of
      moderate UV exposure on outgrowth and malignant progression of primary intestinal
      tumors, which at least in part can be attributed to vitamin D.

PMID- 24890437
TI  - Epidermolysis bullosa acquisita: a retrospective analysis of 12 patients
      evaluated in four tertiary hospitals in Spain.
AB  - BACKGROUND: Epidermolysis bullosa acquisita is an exceedingly rare subepidermal
      blistering disease caused by antibodies against type VII collagen. Studies
      summarizing the clinical and immunological features of this disease in large
      series of patients are scarce. OBJECTIVES: To analyse the clinical and
      immunopathological characteristics, treatment responses and outcomes of 12
      patients with epidermolysis bullosa acquisita from four tertiary hospitals in
      Spain. METHODS: An extensive retrospective review of clinical charts. RESULTS:
      The mean age of onset was 48 years and the mean delay to diagnosis was 20.75
      months. The classical phenotype occurred in 42% of cases, inflammatory in 42% and
      mixed in 17%. Mucosal involvement was present in 75%. Linear IgG deposition along
      the basement membrane zone was consistently present on direct immunofluorescence
      examination. Indirect immunofluorescence study was positive in 67% of the cases.
      Frequently associated diseases were neoplasms (25%), inflammatory bowel disease
      (25%), hepatitis C virus infection (17%) and thyroid dysfunction (17%).
      Therapeutic responses were variable. CONCLUSIONS: The prevalence of neoplasms was
      similar to that seen in inflammatory bowel disease. Multicentric prospective
      studies including larger numbers of patients are required for a better knowledge
      and management of this disease.

PMID- 24890438
TI  - The use of flow cytometry for immunophenotyping lymphoproliferative disorders in
      cats: a retrospective study of 19 cases.
AB  - Flow cytometric immunophenotyping is a useful step in the diagnosis of
      lymphoproliferative malignancies in human and veterinary medicine. The purpose of
      this study was to assess the usefulness of this technique for the diagnosis of
      lymphoproliferative disorders in cats. Nineteen cats were retrospectively
      enrolled in this study and allocated into two groups. Group 1 consisted of 13
      cats with lymphoma, whereas group 2 consisted of 6 cats with non-neoplastic
      lymphoproliferative disorders. Fine-needle aspiration biopsies were analysed by
      flow cytometry in order to evaluate the immunophenotype. Flow cytometric analysis
      identified a neoplastic lymphoid population in 12 of the 13 cats of group 1,
      confirming the diagnosis of lymphoma and further characterizing it. The six cats
      in group 2 showed a mixed lymphoid population, which was not suggestive of a
      neoplastic disorder. Flow cytometry is a valuable and powerful tool for refining
      the diagnosis of feline lymphoproliferative disorders. 

PMID- 24890433
TI  - Pattern recognition receptors and the inflammasome in kidney disease.
AB  - Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain
      receptors (NLRs) are families of pattern recognition receptors that, together
      with inflammasomes, sense and respond to highly conserved pathogen motifs and
      endogenous molecules released upon cell damage or stress. Evidence suggests that
      TLRs, NLRs and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
      inflammasome have important roles in kidney diseases through regulation of
      inflammatory and tissue-repair responses to infection and injury. In this Review,
      we discuss the pathological mechanisms that are related to TLRs, NLRs and NLRP3
      in various kidney diseases. In general, these receptors are protective in the
      host defence against urinary tract infection, but can sustain and self-perpetuate
      tissue damage in sterile inflammatory and immune-mediated kidney diseases. TLRs,
      NLRs and NLRP3, therefore, have become promising drug targets to enable specific
      modulation of kidney inflammation and suppression of immunopathology in kidney
      disease. 

PMID- 24890439
TI  - Mortality from chronic liver diseases in diabetes.
AB  - OBJECTIVES: Mortality from chronic liver diseases (CLDs) is increased in
      diabetes, but little is known about the etiology. The aim of this study was to
      assess mortality rates from CLD by etiology in known diabetic subjects living in
      the Veneto Region, Northern Italy. METHODS: A total of 167,621 diabetic subjects,
      aged 30-89 years (54.6% men), were identified in the year 2007 and their vital
      status was assessed between 2008 and 2010. Standardized mortality ratios (SMR)
      with 95% confidence intervals (CIs) were computed with regional mortality rates
      as reference. The underlying cause of death and all comordidities reported on the
      certificate were scrutinized in order to identify CLD deaths and their main
      etiologies. The latter were grouped into the following three categories: (i)
      virus-related, (ii) alcohol-related, and (iii) non-virus, non-alcohol-related
      (mainly represented by nonalcoholic fatty liver disease, NAFLD). RESULTS:
      Analyses were based upon 473,374 person-years of follow-up and 17,134 deaths. We
      observed an increased risk of dying from CLD in diabetic subjects with an SMR of
      2.47 (95% CI=2.19-2.78) in men and 2.70 (2.24-3.23) in women. SMRs were 2.17
      (1.90-2.47), 2.25 (1.98-2.54), and 2.86 (2.65-3.08) for virus-related, alcohol
      related, and non-virus, non-alcohol-related CLD, respectively. CONCLUSIONS:
      Diabetic patients have a twofold to threefold higher risk of dying of CLD, mainly
      associated with a non-virus and non-alcohol-related etiology, which is largely
      attributable to NAFLD. An early diagnosis and treatment of NAFLD, if any, may
      have a beneficial clinical impact on the survival of diabetic patients.

PMID- 24890440
TI  - Effect of virological response to entecavir on the development of hepatocellular
      carcinoma in hepatitis B viral cirrhotic patients: comparison between compensated
      and decompensated cirrhosis.
AB  - OBJECTIVES: This study aimed to evaluate the risk of development of
      hepatocellular carcinoma (HCC) according to underlying liver status and
      virological response (VR) to entecavir (ETV) in chronic hepatitis B patients with
      cirrhosis. Procollagen III N-terminal peptide (PIIINP) concentration during ETV
      treatment and its association with HCC development were also evaluated. METHODS:
      A total of 306 patients with clinically diagnosed liver cirrhosis were treated
      with ETV for >=12 months and were subsequently followed up for the occurrence of
      HCC (median follow-up duration: 37.0 months). Patients who developed HCC within
      12 months were excluded. VR was defined as a hepatitis B virus DNA level <20
      IU/ml at 12 months after ETV treatment. RESULTS: A total of 209 patients (68.3%)
      had compensated cirrhosis, and the remaining patients (31.7%) had decompensated
      cirrhosis. The 5-year cumulative incidence of HCC was 26.8%. A multivariate Cox
      regression analysis identified the following independent risk factors for
      developing HCC in all the patients: age >50 years (hazard ratio (HR)=8.41; 95%
      confidence interval (CI)=3.86-18.28; P=0.000), male sex (HR=4.24; 95% CI=1.83
      9.81; P=0.001), high serum PIIINP level at 12 months (HR=1.07; 95% CI=1.02-1.13;
      P=0.007), and no VR at 12 months (HR=2.10; 95% CI=1.02-4.33; P=0.043). The
      subgroup analyses showed that no VR at 12 months is a significant risk factor for
      developing HCC in the patients with decompensated cirrhosis (HR=7.74; 95% CI=1.34
      44.78; P=0.022) but not in those with compensated cirrhosis (P=0.749).
      CONCLUSIONS: The antiviral treatment with ETV did not completely eliminate the
      risk of developing HCC in our patients with cirrhosis. However, VR to ETV was
      associated with a low probability that the patients with decompensated cirrhosis
      would develop HCC.

PMID- 24890441
TI  - Nonalcoholic fatty liver disease is underrecognized in the primary care setting.
AB  - OBJECTIVES: The prevalence and disease burden of nonalcoholic fatty liver disease
      (NAFLD) are increasing. Nonetheless, little is known about the processes related
      to identification, diagnosis, and referral of patients with NAFLD in routine
      clinical care. METHODS: Using automated data, we isolated a random sample of
      patients in a Veterans Administration facility who had >=2 alanine transaminase
      (ALT) values >40 IU/ml >6 months apart in the absence of any positive results for
      hepatitis C RNA, hepatitis B surface antigen, or screens for excess alcohol use.
      We conducted a structured medical record review to confirm NAFLD and abstracted
      data from the primary care providers' notes for (i) recognition of abnormal ALT
      levels, (ii) mention of NAFLD as a possible diagnosis, (iii) recommendations for
      diet or exercise, and (d) referral to a specialist for further NAFLD evaluation.
      Using a multilevel logistic regression model, we identified patient demographic,
      clinical, comorbidity, and health-care utilization factors associated with
      recognition and receipt of early NAFLD care. RESULTS: Of 251 patients identified
      with NAFLD by our methods, 99 (39.4%) had documentation in medical record notes
      of abnormal ALT, 54 (21.5%) had NAFLD mentioned as a possible diagnosis, 37
      (14.7%) were counseled regarding diet and exercise, and 26 (10.4%) were referred
      to a specialist. Only the magnitude of ALT elevation (adjusted odds ratio (OR)
      for ALT >80 IU/ml vs. <80 IU/ml=4.4, 95% confidence interval (CI)=2.65-7.30) and
      proportion of elevation (adjusted OR for >50% vs. <50% of ALT values >40
      IU/ml=1.8, 95% CI=1.03-3.14) were associated with receiving specified NAFLD care.
      Only 3% of patients at a high risk of fibrosis (NAFLD fibrosis score >0.675) were
      referred to specialists. CONCLUSIONS: Most patients in care who may have NAFLD
      are not being recognized and evaluated for this condition. Our data suggest that
      providers may be using an incorrect heuristic in delivering NAFLD care by
      concentrating on those with high ALT levels.

PMID- 24890442
TI  - Fecal microbiota transplant for treatment of Clostridium difficile infection in
      immunocompromised patients.
AB  - OBJECTIVES: Patients who are immunocompromised (IC) are at increased risk of
      Clostridium difficile infection (CDI), which has increased to epidemic
      proportions over the past decade. Fecal microbiota transplantation (FMT) appears
      effective for the treatment of CDI, although there is concern that IC patients
      may be at increased risk of having adverse events (AEs) related to FMT. This
      study describes the multicenter experience of FMT in IC patients. METHODS: A
      multicenter retrospective series was performed on the use of FMT in IC patients
      with CDI that was recurrent, refractory, or severe. We aimed to describe rates of
      CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item
      questionnaire soliciting demographic and pre- and post-FMT data was completed for
      99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes
      included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such
      as death or hospitalization within 12 weeks of FMT, (iii) infection within 12
      weeks of FMT, and (iv) AEs (related and unrelated) to FMT. RESULTS: Cases
      included adult (75) and pediatric (5) patients treated with FMT for recurrent
      (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and
      severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean
      follow-up period between FMT and data collection was 11 months (range 3-46
      months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19),
      oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease
      (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after
      a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks
      post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI.
      Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks
      post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks
      of FMT, one of which was the result of aspiration during sedation for FMT
      administered via colonoscopy; the other was unrelated to FMT. None suffered
      infections definitely related to FMT, but two patients developed unrelated
      infections and five had self-limited diarrheal illness in which no causal
      organism was identified. One patient had a superficial mucosal tear caused by the
      colonoscopy performed for the FMT, and three patients reported mild, self-limited
      abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease
      flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy
      related to course of UC >100 days after FMT. CONCLUSIONS: This series
      demonstrates the effective use of FMT for CDI in IC patients with few SAEs or
      related AEs. Importantly, there were no related infectious complications in these
      high-risk patients.

PMID- 24890444
TI  - Role of psychosocial factors and serotonin transporter genotype in male
      adolescent criminal activity.
AB  - INTRODUCTION: Violent behavior is influenced by various environmental factors and
      the serotonergic circuitry alike. Nevertheless, studies on relations among genes,
      personality, social environment, and juvenile violent behavior are limited, and
      there is no such study in China. METHODS: In the current study, we aimed to
      investigate the contribution of serotonin transporter (5-HTT) polymorphisms to
      the development of violence and to explore the relations among genes,
      personality, social environment, and juvenile violent behavior in China. We
      recruited 213 male adolescents with violent crime history and 145 male
      adolescents without violent crime history. The association between each risk
      factor and violent behavior for all the participants was examined, and the
      interrelation of the domains (personality, family, social support, coping style,
      impulsivity, and aggression) and the adolescents' violent behavior was analyzed.
      Chi-square test was used to examine the association between genotypes and violent
      behavior. RESULTS: Adolescents with a violent crime history had lower education
      levels, higher neuroticism and psychoticism, but lower dissimulate. Social
      support and coping style were significantly associated with their criminal
      behaviors. DISCUSSION: The 5-HTTLPR genotype distributions differed significantly
      between the violent and nonviolent groups.

PMID- 24890443
TI  - A patient-blinded randomized, controlled trial comparing air insufflation, water
      immersion, and water exchange during minimally sedated colonoscopy.
AB  - OBJECTIVES: Minimal sedation obviates patient recovery burdens, but intolerable
      pain limits success of cecal intubation. Painless or minimally uncomfortable
      insertion ensures success of cecal intubation, current patient satisfaction, and
      willingness to repeat future colonoscopy with minimal sedation. Water immersion
      (WI) and water exchange (WE), when separately compared with air insufflation
      (AI), significantly reduced insertion pain. To assess comparative effectiveness,
      we conducted a randomized controlled trial with head-to-head comparison of these
      three methods. We hypothesized that WE could produce the highest proportion of
      patients reporting painless insertion. METHODS: This prospective patient-blinded
      trial (NCT01535326) enrolled minimally sedated (25 mg intramuscular meperidine)
      patients randomized to AI, WI, or WE (90 patients/group) to aid insertion. The
      previously validated primary outcome was the proportion of patients reporting
      painless insertion. RESULTS: Painless insertion was reported by 30.0% (AI), 43.3%
      (WI), and 61.1% (WE) of patients (P<0.001). Multivariate logistic regression
      analysis revealed that, after adjusting for gender, body mass index, abdominal
      compression, position change, insertion time to cecum, and length of scope at
      cecum, only WE was significantly associated with painless insertion compared with
      AI (odds ratio (OR)=0.08, 95% confidence interval (CI)=0.03-0.24, P<0.001) or WI
      (OR=0.14, 95% CI=0.05-0.40, P<0.001). Adenoma detection rate (ADR) in the right
      (cecum and ascending) colon was 11.1% (AI), 14.4% (WI), and 26.7% (WE) (P=0.015).
      The limitations included single site study with unblinded colonoscopist and
      assistant. CONCLUSIONS: This head-to-head comparison of AI vs. WI vs. WE
      confirmed that WE was superior to WI and AI, with a significantly greater
      proportion of patients reporting painless insertion. The significantly higher ADR
      in the right colon in the WE group warrants further investigations.

PMID- 24890446
TI  - Persistent left superior vena cava draining into the pulmonary venous system
      discovered after central venous catheter placement.

PMID- 24890445
TI  - Prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission
      tomography/CT volume-based parameters in patients with oropharyngeal squamous
      cell carcinoma with known p16 and p53 status.
AB  - BACKGROUND: The purpose of this study was to determine whether pretreatment 18F
      fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) volume-based
      parameters, such as metabolic tumor volume and total lesion glycolysis, add more
      prognostic information in patients with oropharyngeal squamous cell carcinoma
      (SCC). METHODS: The subjects were 47 patients with oropharyngeal SCC who
      underwent 18F-FDG PET/CT before any treatment and followed by definitive therapy.
      PET parameters (metabolic tumor volume and total lesion glycolysis) and tumor
      p16/p53 status were evaluated retrospectively. Univariate and multivariate
      analyses were performed for disease-free survival (DFS), disease-specific
      survival (DSS), and overall survival (OS). RESULTS: All volume-based PET
      parameters were found to be significant prognostic factors for DFS, DSS, and OS
      in univariate analysis. In multivariate analysis, only metabolic tumor volume for
      total tumor lesions (cutoff 65) retained an independent association with DFS,
      DSS, and OS. CONCLUSION: Metabolic tumor volume for total tumor lesions may be a
      predictive marker for survival outcomes in patients with oropharyngeal SCC with
      known p16/p53 status.

PMID- 24890447
TI  - Long term results of lumbar sequestrectomy versus aggressive microdiscectomy.
AB  - It remains unknown whether aggressive microdiscectomy (AD) provides a better
      outcome than simple sequestrectomy (S) with little disc disruption for the
      treatment of lumbar disc herniation with radiculopathy. We compared the long term
      results for patients with lumbar disc herniation who underwent either AD or S.
      The patients were split into two groups: 85 patients who underwent AD in Group A
      and 40 patients who underwent S in Group B. The patients were chosen from a
      cohort operated on by the same surgeon using either of the two techniques between
      2003 and 2008. The demographic characteristics were similar. The difference in
      complication rates between the two groups was not statistically significant.
      During the first 10 days post-operatively, the Visual Analog Scale score for back
      pain was 4.1 in Group A and 2.1 in Group B, and the difference was statistically
      significant (p<0.005). The Oswestry Disability Index score was 11% in Group A and
      19% in Group B at the last examination. The reherniation rate was 1.5% in Group A
      and 4.1% in Group B (p<0.005). We argue that reherniation rates are much lower
      over the long term when AD is used with microdiscectomy. AD increases back pain
      for a short time but does not change the long term quality of life. To our
      knowledge this is the first study with a very long term follow-up showing that
      reherniation is three times less likely after AD than S.

PMID- 24890448
TI  - Neural murmurations. Comment on "Understanding brain networks and brain
      organization" by Luiz Pessoa.

PMID- 24890449
TI  - Thymoquinone induces apoptosis in human colon cancer HCT116 cells through
      inactivation of STAT3 by blocking JAK2- and Src-mediated phosphorylation of EGF
      receptor tyrosine kinase.
AB  - Thymoquinone (TQ), a compound isolated from black seed oil (Nigella sativa), has
      been reported to possess anti-inflammatory and anticancer activities. However,
      the molecular mechanisms underlying the anticancer effects of TQ remain poorly
      understood. In the present study, we found that TQ significantly reduced the
      viability of human colon cancer HCT116 cells in a concentration- and time
      dependent manner. Treatment of cells with TQ induced apoptosis, which was
      associated with the upregulation of Bax and inhibition of Bcl-2 and Bcl-xl
      expression. TQ also activated caspase-9,-7, and -3, and induced the cleavage of
      poly-(ADP-ribose) polymerase (PARP). Pretreatment with a pan-caspase inhibitor, z
      VAD-fmk, abrogated TQ-induced apoptosis by blocking the cleavage of caspase-3 and
      PARP. Treatment of cells with TQ also diminished the constitutive
      phosphorylation, nuclear localization and the reporter gene activity of signal
      transducer and activator of transcription-3 (STAT3). TQ attenuated the expression
      of STAT3 target gene products, such as survivin, c-Myc, and cyclin-D1, -D2, and
      enhanced the expression of cell cycle inhibitory proteins p27 and p21. Treatment
      with TQ attenuated the phosphorylation of upstream kinases, such as Janus
      activated kinase-2 (JAK2), Src kinase and epidermal growth factor receptor (EGFR)
      tyrosine kinase. Pharmacological inhibition of JAK2 and Src blunted tyrosine
      phosphorylation of EGFR and STAT3, while treatment with an EGFR tyrosine kinase
      inhibitor gefitinib inhibited phosphorylation of STAT3 without affecting that of
      JAK2 and Src in HCT116 cells. Collectively, our study revealed that TQ induced
      apoptosis in HCT116 cells by blocking STAT3 signaling via inhibition of JAK2- and
      Src-mediated phosphorylation of EGFR tyrosine kinase.

PMID- 24890450
TI  - Breast cancer: from Halsted to Harney.
AB  - The management of breast cancer has evolved in the last 40 years to now encompass
      not only treating the cancer in the most effective way, but also to detect and
      treat cancers before they can pose a risk to patients. This evolution in therapy
      and diagnostics has moved away from treating patients with the maximum amount of
      therapy they can tolerate towards a new paradigm where patents receive the
      minimum treatment to be most efficacious.

PMID- 24890451
TI  - Cancer treatment and survivorship statistics, 2014.
AB  - The number of cancer survivors continues to increase due to the aging and growth
      of the population and improvements in early detection and treatment. In order for
      the public health community to better serve these survivors, the American Cancer
      Society and the National Cancer Institute collaborated to estimate the number of
      current and future cancer survivors using data from the Surveillance,
      Epidemiology, and End Results (SEER) program registries. In addition, current
      treatment patterns for the most common cancer types are described based on
      information in the National Cancer Data Base and the SEER and SEER-Medicare
      linked databases; treatment-related side effects are also briefly described.
      Nearly 14.5 million Americans with a history of cancer were alive on January 1,
      2014; by January 1, 2024, that number will increase to nearly 19 million. The 3
      most common prevalent cancers among males are prostate cancer (43%), colorectal
      cancer (9%), and melanoma (8%), and those among females are cancers of the breast
      (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of
      survivors varies substantially by cancer type. For example, the majority of
      prostate cancer survivors (62%) are aged 70 years or older, whereas less than one
      third (32%) of melanoma survivors are in this older age group. It is important
      for clinicians to understand the unique medical and psychosocial needs of cancer
      survivors and to proactively assess and manage these issues. There are a growing
      number of resources that can assist patients, caregivers, and health care
      providers in navigating the various phases of cancer survivorship.

PMID- 24890452
TI  - Street intercept method: an innovative approach to recruiting young adult high
      risk drinkers.
AB  - INTRODUCTION AND AIMS: Many young adults are risky drinkers who are often missed
      by general population surveys. The aim of the present study was to assess factors
      affecting participation rates in a street intercept approach to recruiting young
      adult bar-goers for an online survey. DESIGN AND METHODS: Two hundred eighty
      seven young adults were approached as they entered the bar district of a medium
      sized city on two consecutive weekend nights. Of these, 170 met eligibility
      requirements and were invited to complete a 2 min street survey for which they
      were paid $5 and given a gift card for $50 or $100 to be redeemed when they
      completed a follow-up online survey. RESULTS: Sixty-one per cent of eligible
      persons (n = 104) participated in the street survey, with greater participation
      on the second night (74% vs. 50%). Sixty-eight per cent (n = 71) of those who
      participated in the street survey completed the online survey, with no
      differences in response by age or student status; however, men were significantly
      more likely to complete the online survey if they received the higher incentive,
      had consumed less alcohol and were recruited before midnight. The larger
      incentive was especially effective at increasing completion rates for men who had
      consumed a larger amount of alcohol. DISCUSSION AND CONCLUSIONS: Street intercept
      is an effective and efficient recruitment method that can measure both drinking
      and other experiences in the event and link these data to information collected
      in follow-up research. Unlike recruitment through convenience samples, response
      rates and response bias can also be assessed.

PMID- 24890453
TI  - Near infrared organic semiconducting materials for bulk heterojunction and dye
      sensitized solar cells.
AB  - Dye sensitized solar cells (DSSCs) and bulk heterojunction (BHJ) solar cells have
      been the subject of intensive academic interest over the past two decades, and
      significant commercial effort has been directed towards this area with the vison
      of developing the next generation of low cost solar cells. Materials development
      has played a vital role in the dramatic improvement of both DSSC and BHJ solar
      cell performance in the recent years. Organic conjugated polymers and small
      molecules that absorb solar light in the visible and near infrared (NIR) regions
      represent a class of emering materials and show a great potential for the use of
      different optoelectronic devices such as DSSCs and BHJ solar cells. This account
      describes the emering class of near infrared (NIR) organic polymers and small
      molecules having donor and acceptors units, and explores their potential
      applications in the DSSCs and BHJ solar cells. 

PMID- 24890454
TI  - Towards an ecological understanding of morphological evolution.
AB  - The roots of modern evo-devo can be traced back to the comparative anatomy of the
      19th century. Inheriting from this tradition, the field has maintained a
      mechanistic approach to understanding the origins of distinct animal
      morphologies. While this focus has produced a valuable body of work, we argue
      here that a fuller understanding of why species diverge morphologically must be
      centered on the selective forces driving divergence, and these forces ultimately
      reside in the ecological context in which organisms live and reproduce. We
      discuss reasons why we expect many morphological novelties to evolve largely
      secondarily to, and often as a by-product of, primary selection on life-history
      traits. By shifting the focus to proximate evolutionary causes, our perspective
      necessarily prioritises selection experiments as a means of empirical testing. We
      outline experimental approaches designed to dissect the role of ecological
      variables in the evolution of animal development and morphology, and we show how
      methods and advances in fields as diverse as population genomics and ecological
      stoichiometry can contribute to progress in this direction.

PMID- 24890455
TI  - Radiological evidence for the triple bundle anterior cruciate ligament.
AB  - The anterior cruciate ligament (ACL) has traditionally been described as having
      two bundles--one anteromedial and one posterolateral. This has been challenged by
      studies proposing the existence of a third, intermediate, bundle with distinct
      functional significance, an arrangement that has been described in a number of
      domesticated animal species. No radiological evidence for the triple bundle ACL
      has previously been described. A prevalence study was carried out on 73
      consecutive human knee magnetic resonance (MR) studies to determine the number of
      visible bundles, excluding individuals with a history of ACL injury or mucoid
      degeneration. A triple bundle ACL was demonstrated in 15 out of 73 human knees
      (20.5%, 95% confidence interval 12.9-31.2%). This is the first radiological
      description of the human triple bundle ACL. There was MR imaging evidence of a
      triple bundle ACL in approximately one fifth of human knees in this study.

PMID- 24890456
TI  - Out of sight, but not out of mind? Greater reported pain in patients who
      spontaneously look away during venepuncture.
AB  - BACKGROUND: Various external factors can influence patients' experiences of
      noxious stimuli, but little is known of how patients' natural behaviour may be
      relevant. We ascertained how often patients spontaneously look or look away
      during venepuncture and associated reports of pain during a previously reported
      experimental randomized study. The study was conducted in the outpatient
      department of a U.K. district general hospital. METHODS: Patients were randomized
      to hearing 'sharp scratch' or the verbal cue 'ready?' immediately before
      venepuncture. Whether patients looked or looked away during needle insertion was
      recorded. Patients were asked to rate their pain using a verbal numerical rating
      score (VNRS) and verbal response scale (VRS). RESULTS: One hundred ninety-two
      patients were included; mean age 51.7 years, 55% male. During needle insertion,
      73% spontaneously looked away, whereas 27% looked. There was no significant
      difference in the proportion of these patients assigned to the 'sharp scratch' or
      'ready?' groups, nor was there any difference in mean age or gender. For the
      group that looked, mean VNRS was 0.48 and VRS was 1.27, significantly less than
      the group that looked away (mean VNRS 0.94, p = 0.014; VRS 1.61, p = 0.002). As
      previously reported, pain ratings between 'sharp scratch' and 'ready?' groups
      were not significantly different. CONCLUSIONS: Almost three quarters of patients
      spontaneously look away during venepuncture, but their pain ratings are almost
      twice that of the quarter of patients who look. It is unclear why this may be,
      but previous experimental studies indicate that observing the body when a noxious
      stimulus is applied can have an analgesic effect.

PMID- 24890457
TI  - In vitro effect of IL-2 in combination with pazopanib or sunitinib on lymphocytes
      function and apoptosis of RCC cells.
AB  - OBJECTIVE: Combination of immunotherapy with tyrosine kinase inhibitors (TKIs)
      has been used with some success for the treatment of metastatic renal cell
      carcinoma. Herein we evaluate the in vitro effect of high-dose interleukin-2
      (HDIL-2) and pazopanib or sunitinib on the lymphocyte function and on induction
      of apoptosis in renal cell carcinoma (RCC) cell lines. METHODS: Peripheral blood
      mononuclear cells (PBMCs) isolated from healthy donors or RCC patients were
      treated with different HDIL-2/TKI combinations. Effects of different combinations
      on proliferation and cytotoxic activity of PBMCs were evaluated, in addition to
      their effect on apoptosis of three different RCC cell lines. RESULTS: While
      sunitinib did not inhibit the proliferation of various immune cells induced by
      HDIL-2, pazopanib appeared to inhibit the HDIL-2-induced proliferation of these
      cells. Interestingly, none of the HDIL-2/TKI combinations appeared to compromise
      the functional properties of these cells. Additionally, significant proportion of
      RCC cell lines treated with pazopanib alone underwent apoptosis, while the
      proportions of apoptotic cells post-HDIL-2 or sunitinib were not different from
      the background. Furthermore, the combination of HDIL-2/pazopanib did not inhibit
      the pazopanib-induced RCC apoptosis. CONCLUSION: The combination of HDIL-2 with
      either pazopanib or sunitinib exerts different anticancer mechanisms that could
      enhance the treatment efficacy.

PMID- 24890458
TI  - Synthesis of pi-extended dibenzophospholes by intramolecular radical cyclization
      and their properties.
AB  - Intramolecular radical cyclization of phosphine oxides (R(1)R(2)P(O)H) induced by
      radical generators affords the corresponding dibenzophosphole oxides in excellent
      yields. By applying this method, linearly pi-extended ladder-type
      dibenzophosphole oxides were successfully synthesized. 

PMID- 24890459
TI  - Extraction and preconcentration of tylosin from milk samples through
      functionalized TiO2 nanoparticles reinforced with a hollow fiber membrane as a
      novel solid/liquid-phase microextraction technique.
AB  - The aim of this study was to introduce a novel, simple, and highly sensitive
      preparation method for determination of tylosin in different milk samples. In the
      so-called functionalized TiO2 hollow fiber solid/liquid-phase microextraction
      method, the acceptor phase is functionalized TiO2 nanoparticles that are
      dispersed in the organic solvent and held in the pores and lumen of a porous
      polypropylene hollow fiber membrane. An effective functionalization of TiO2
      nanoparticles has been done in the presence of aqueous H2 O2 and a mild acidic
      ambient under UV irradiation. This novel extraction method showed excellent
      extraction efficiency and a high enrichment factor (540.2) in comparison with
      conventional hollow fiber liquid-phase microextraction. All the experiments were
      monitored at lambdamax = 284 nm using a simple double beam UV-visible
      spectrophotometer. A Taguchi orthogonal array experimental design with an OA16
      (4(5) ) matrix was employed to optimize the factors affecting the efficiency of
      hollow fiber solid/liquid-phase microextraction such as pH, stirring rate, salt
      addition, extraction time, and the volume of donor phase. This developed method
      was successfully applied for the separation and determination of tylosin in milk
      samples with a linear concentration range of 0.51-7000 MUg/L (r(2) = 0.991) and
      0.21 MUg/L as the limit of detection. 

PMID- 24890461
TI  - Reply: To PMID 23929603.

PMID- 24890460
TI  - HSP70 inhibits high glucose-induced Smad3 activation and attenuates epithelial-to
      mesenchymal transition of peritoneal mesothelial cells.
AB  - Heat shock proteins (HSPs) are molecular chaperones that were initially
      identified as proteins expressed following exposure of cells to environmental
      stress. However, the function of HSPs in epithelial-to-mesenchymal transition
      (EMT) of peritoneal mesothelial cells remains unknown. In the present study, the
      regulation of HSPs and their function in cell EMT, particularly in rat peritoneal
      mesothelial cells (RPMCs), and the surrounding glucose concentrations and the
      molecular mechanism involved were investigated. This study explored the effect of
      HSP70 on high glucose (HG)-induced EMT by overexpression and small interfering
      RNA (siRNA) knockdown of HSP70, as well as the underlying molecular mechanisms.
      It was found that HSP70 inhibits HG-induced EMT by modulating Smad expression and
      activation. HSP70 overexpression inhibited phosphorylation and nuclear
      translocation of p-Smad3 and p-Smad4, while siRNA of HSP70 enhanced HG-induced
      Smad3 and Smad4 phosphorylation and EMT. Furthermore, HSP70 suppressed EMT by
      inhibiting the generation of reactive oxygen species (ROS) induced by HG. In
      conclusion, HSP70 inhibits EMT of peritoneal mesothelial cells primarily by
      exerting domain-specific effects on Smad3 and Smad4 activation and reducing the
      release of ROS. HSP70 may be a novel therapeutic target for peritoneal dialysis
      patients with peritoneal fibrosis. 

PMID- 24890462
TI  - Carbon monoxide-bound red blood cell resuscitation ameliorates hepatic injury
      induced by massive hemorrhage and red blood cell resuscitation via hepatic
      cytochrome P450 protection in hemorrhagic shock rats.
AB  - Red blood cell (RBC) transfusions are the gold standard in cases of massive
      hemorrhage, but induce hepatic ischemia-reperfusion injury, a serious
      complication associated with hemorrhage and RBC resuscitation. Thus, the
      development of a novel resuscitable fluid that is not associated with hepatic
      ischemia-reperfusion injury would be desirable. It was reported that exogenous
      carbon monoxide (CO) treatment ameliorated hepatic ischemia-reperfusion injury
      accompanying liver transplantation. This suggests that transfusions with CO-bound
      RBC (CO-RBC) might protect against hepatic ischemia-reperfusion injury following
      massive hemorrhage and resuscitation compared with RBC resuscitation. To
      investigate this, we created a hemorrhagic shock model rat, followed by
      resuscitation with RBC and CO-RBC. Hepatic ischemia-reperfusion injury and the
      destruction of hepatic cytochrome P450 (CYP) were significantly ameliorated in
      the CO-RBC resuscitation group compared with the RBC resuscitation group. The
      free heme derived from the destruction of hepatic CYP was correlated with hepatic
      oxidation and injury, suggesting that CO-RBC was a major factor in the
      amelioration of hepatic ischemia-reperfusion injury induced by hemorrhage and
      resuscitation via hepatic CYP protection. These results indicate that CO-RBC has
      potential for use as a resuscitative fluid in blood transfusion and does not
      suffer from the limitations associated with the RBC transfusions that are
      currently in use.

PMID- 24890464
TI  - Depletion and capture: revisiting "the source of water derived from wells".
AB  - A natural consequence of groundwater withdrawals is the removal of water from
      subsurface storage, but the overall rates and magnitude of groundwater depletion
      and capture relative to groundwater withdrawals (extraction or pumpage) have not
      previously been well characterized. This study assesses the partitioning of long
      term cumulative withdrawal volumes into fractions derived from storage depletion
      and capture, where capture includes both increases in recharge and decreases in
      discharge. Numerical simulation of a hypothetical groundwater basin is used to
      further illustrate some of Theis' (1940) principles, particularly when capture is
      constrained by insufficient available water. Most prior studies of depletion and
      capture have assumed that capture is unconstrained through boundary conditions
      that yield linear responses. Examination of real systems indicates that capture
      and depletion fractions are highly variable in time and space. For a large sample
      of long-developed groundwater systems, the depletion fraction averages about 0.15
      and the capture fraction averages about 0.85 based on cumulative volumes. Higher
      depletion fractions tend to occur in more arid regions, but the variation is high
      and the correlation coefficient between average annual precipitation and
      depletion fraction for individual systems is only 0.40. Because 85% of long-term
      pumpage is derived from capture in these real systems, capture must be recognized
      as a critical factor in assessing water budgets, groundwater storage depletion,
      and sustainability of groundwater development. Most capture translates into
      streamflow depletion, so it can detrimentally impact ecosystems. 

PMID- 24890463
TI  - A systematic review of systemic medications for pustular psoriasis in pediatrics.
AB  - There is lack of information and evidence-based studies on the treatment of
      pediatric pustular psoriasis. Previous reports have emphasized the limitations of
      the existing data and encouraged the exploration of therapy optimization through
      more structured research. The objective of the current study was to perform a
      systematic review of systemic interventions for pediatric pustular psoriasis with
      an emphasis on clinical response and treatment outcomes. A systematic literature
      search was conducted using the PubMed and Embase databases from 1982 to 2012. Of
      632 references identified, 14 met our inclusion criteria and were included in the
      analysis. A cohort of eight patients from the Hospital for Sick Children,
      Toronto, Canada, was also included. Information was limited to systemic
      treatments in children. Only English- and Spanish-language articles were
      included. Information was gathered from 24 patients, 22 of whom (92%) presented
      with generalized pustular psoriasis and 2 (8%) with acral distribution. The mean
      age at presentation was 6.3 +/- 4.9 years. More than one intervention was
      required in 12 (50%) cases. The most common therapies used for generalized
      pustular psoriasis were acitretin, cyclosporine, and methotrexate. We identified
      that there is lack of information regarding long-term response to systemic drugs
      because the data were focused on treatment initiation. Treatment of pustular
      psoriasis in pediatrics is challenging. Although acitretin, methotrexate, and
      cyclosporine seem to control generalized pustular psoriasis within 3 months of
      therapy initiation, information on long-term follow-up is lacking. Furthermore,
      physicians may encounter difficulties after discontinuing or tapering
      medications. 

PMID- 24890465
TI  - Providing alcohol to underage youth: the view from young adulthood.
AB  - BACKGROUND: Many underage drinkers obtain alcohol from legal-age family, friends,
      and acquaintances. This study aimed to understand the attitudes and behaviors of
      young adults related to providing alcohol to underage drinkers. METHODS:
      Participants were 755 current or recent college students of legal drinking age
      (ages 22 to 26) who were approached by a minor to provide alcohol at least once
      since turning 21. Interviewers assessed frequency of providing alcohol,
      relationship to the recipients, and general attitudes about providing alcohol to
      minors. Separate questions asked about younger (under 18) and older (18 to 20)
      minors. Correlates and predictors of provision and frequency of provision were
      examined via logistic regression and Poisson regression, focusing on
      demographics, sensation-seeking, behavioral dysregulation, age at first drink,
      parental history of alcohol problems, fraternity/sorority involvement, attitudes
      about provision, violations, peer drinking norms, and alcohol use disorder (AUD)
      risk during and post-college. RESULTS: Most participants (84.6%) provided alcohol
      to minors at least once. Provision to older minors was more prevalent (82.8%)
      than to younger minors (20.7%); it was also more frequent. Few (2.4%) were ever
      caught providing alcohol. Recipients were more commonly friends or family members
      rather than acquaintances or strangers. Legal concerns about providing alcohol
      (82.5 and 53.7% for younger and older minors, respectively) were more prevalent
      than health concerns (55.7 and 9.5%). Legal concerns consistently predicted lower
      likelihood of provision, independent of demographics. Health concerns and lower
      post-college AUD risk scores also independently predicted lower likelihood of
      provision, but only to older minors. Fraternity/sorority involvement and higher
      peer drinking norms were associated with higher provision frequency, whereas
      legal concerns and college violations were associated with lower provision
      frequency. CONCLUSIONS: Young adults who have recently turned 21 could represent
      an important target for prevention strategies to reduce underage drinking on
      college campuses. More research is needed to understand the motivations of young
      adults who provide alcohol to underage drinkers.

PMID- 24890466
TI  - Strongyloides stercoralis infection in allogeneic stem cell transplant: a case
      report and review of the literature.
AB  - Strongyloides stercoralis infections may be documented in low-endemicity areas,
      particularly in immigrants from endemic areas. The case of a patient from
      Bangladesh, an immigrant to Italy who developed a S. stercoralis infection after
      allogeneic stem cell transplant, is described, and 7 further cases are reviewed.
      Because of the atypical clinical presentation, the low predictive role of the
      eosinophil count, and the low sensitivity of the microbiological tests, diagnosis
      of strongyloidiasis is a challenging problem. When a case of S. stercoralis
      infection is suspected, previous exposure may be the only clue to guide the
      diagnostic approach.

PMID- 24890468
TI  - Report of the joint ESOT and TTS basic science meeting 2013: current concepts and
      discoveries in translational transplantation.
AB  - A joint meeting organized by the European (ESOT) and The Transplantation (TTS)
      Societies for basic science research was organized in Paris, France, on November
      7-9, 2013. Focused on new ideas and concepts in translational transplantation,
      the meeting served as a venue for state-of-the-art developments in basic
      transplantation immunology, such as the potential for tolerance induction through
      regulation of T-cell signaling. This meeting report summarizes important insights
      which were presented in Paris. It not only offers an overview of established
      aspects, such as the role of Tregs in transplantation, presented by Nobel
      laureate Rolf Zinkernagel, but also highlights novel facets in the field of
      transplantation, that is cell-therapy-based immunosuppression or composite tissue
      transplantation as presented by the emotional story given by Vasyly Rohovyy, who
      received two hand transplants. The ESOT/TTS joint meeting was an overall
      productive and enjoyable platform for basic science research in translational
      transplantation and fulfilled all expectations by giving a promising outlook for
      the future of research in the field of immunological transplantation research. 

PMID- 24890467
TI  - Neurologic indications for therapeutic plasma exchange: 2013 update.
AB  - Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of
      conditions. This concise review considers the most common neurologic indications
      for TPE. It focuses on Guillain-Barre syndrome and myasthenia gravis and also the
      role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton
      syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic
      polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive
      multifocal leukoencephalopathy. As with any treatment, the proven efficacy, cost,
      side effects, and availability must be considered before initiation of therapy.

PMID- 24890471
TI  - Saccade deficits in amnestic mild cognitive impairment resemble mild Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a disorder of progressive memory loss and executive
      dysfunction. Little is known about the progression from amnestic mild cognitive
      impairment (aMCI; isolated memory loss) to AD. Studies have found impairments in
      mild-stage AD and aMCI in specific tests of executive function. Here, we used
      objective saccade tasks to determine if they can effectively assess executive
      function deficits otherwise assessed by neuropsychological testing. To determine
      which executive function deficits the saccade tasks are most sensitive to, we
      also investigated the relationship between performance on saccade tasks and
      neuropsychological test scores. Twenty-two aMCI patients (63-90 years), 24 mild
      AD patients (61-87 years) and 76 healthy controls (60-85 years) performed a
      battery of neuropsychological tests, and two saccade tasks designed to probe
      sensory, motor and cognitive function. The prosaccade task requires a fast,
      automatic saccade toward an eccentric visual stimulus. The antisaccade task
      requires additional executive processing to inhibit the automatic prosaccade
      toward the stimulus, so that a voluntary saccade can be initiated to a location
      opposite the stimulus. Antisaccade performance was impaired similarly in aMCI and
      AD patients relative to controls; both groups were slower to initiate correct
      antisaccades and they made more direction errors (erroneous prosaccades),
      suggesting similar brain deficits. Scores on the Stroop task were inversely
      correlated with the percentage of short-latency direction errors in the
      antisaccade task for controls and aMCI patients, whereas other more global
      measures of executive function were not related to saccade measures in any
      subject group. Our results show that the antisaccade task is useful for detecting
      executive dysfunction in aMCI and AD, especially dysfunction in selective
      attention. Saccade tasks may therefore have potential to assess executive
      dysfunction when use of neuropsychological tests is not possible. 

PMID- 24890472
TI  - Bacterial community structure and activity of sulfate reducing bacteria in a
      membrane aerated biofilm analyzed by microsensor and molecular techniques.
AB  - The activities and vertical spatial distribution of sulfate reducing bacteria
      (SRB) in an oxygen (O2 )-based membrane aerated biofilm (MAB) were investigated
      using microsensor (O2 and H2 S) measurements and molecular techniques (polymerase
      chain reaction-denaturing gradient gel electrophoresis [PCR-DGGE] and
      fluorescence in situ hybridization [FISH]). The O2 concentration profile revealed
      that O2 penetrated from the bottom (substratum) of the gas permeable membrane,
      and was gradually consumed within the biofilm until it was completely depleted
      near the biofilm/bulk liquid interface, indicating oxic and anoxic zone in the
      MAB. The H2 S concentration profile showed that H2 S production was found in the
      upper 285 um of the biofilm, indicating a high activity of SRB in this region.
      The results from DGGE of the PCR-amplified dissimilatory sulfite reductase
      subunit B (dsrB) gene and FISH showed an uneven spatial distribution of SRB. The
      maximum SRB biomass was located in the upper biofilm. The information from the
      molecular analysis can be supplemented with that from microsensor measurements to
      better understand the microbial community and activity of SRB in the MAB.

PMID- 24890470
TI  - The highs and lows of beta activity in cortico-basal ganglia loops.
AB  - Oscillatory activity in the beta (13-30 Hz) frequency band is widespread in
      cortico-basal ganglia circuits, and becomes prominent in Parkinson's disease
      (PD). Here we develop the hypothesis that the degree of synchronization in this
      frequency band is a critical factor in gating computation across a population of
      neurons, with increases in beta band synchrony entailing a loss of information
      coding space and hence computational capacity. Task and context drive this
      dynamic gating, so that for each state there will be an optimal level of network
      synchrony, and levels lower or higher than this will impair behavioural
      performance. Thus, both the pathological exaggeration of synchrony, as observed
      in PD, and the ability of interventions like deep brain stimulation (DBS) to
      excessively suppress synchrony can potentially lead to impairments in behavioural
      performance. Indeed, under physiological conditions, the manipulation of
      computational capacity by beta activity may itself present a mechanism of action
      selection and maintenance. 

PMID- 24890473
TI  - Iatrogenic Kaposi's sarcoma in nasal cavity: a case report.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is an uncommon borderline vascular tumor
      involving mostly the cutaneous and mucosal sites of the body. Among the four
      distinctly clinicopathological presentations of KS, the iatrogenic form
      principally occurs in kidney transplant recipients receiving immunosuppressive
      therapy. It rarely occurs in the head and neck region as primary site or in other
      groups of patients under immunosuppressive therapy. CASE PRESENTATION: We present
      of the case of a patient with right nose KS. The patient had history of systemic
      lupus erythematosus (SLE) and was under immunosuppressive therapy. CONCLUSION:
      Once we keep KS in mind, the definite diagnosis can be made using routine
      histological examination and immunohistochemical study despite the rarity of the
      disease in this site.

PMID- 24890474
TI  - A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry
      method for the determination of dienogest in human plasma and its pharmacokinetic
      applications under fasting.
AB  - A simple, rapid and sensitive analytical method using liquid chromatography
      coupled to tandem mass spectrometry (LC-MS/MS) detection with positive ion
      electrospray ionization was developed for the determination of dienogest in human
      K2 EDTA plasma using levonorgestrel d6 as an internal standard (IS). Dienogest
      and IS were extracted from human plasma using simple liquid-liquid extraction.
      Chromatographic separation was achieved on a Zorbax XDB-Phenyl column (4.6 * 75
      mm, 3.5 um) under isocratic conditions using acetonitrile-5 mm ammonium acetate
      (70:30, v/v) at a flow rate of 0.60 mL/min. The protonated precursor to product
      ion transitions monitored for dienogest and IS were at m/z 312.30 -> 135.30 and
      319.00 -> 251.30, respectively. The method was validated with a linearity range
      of 1.003-200.896 ng/mL having a total analysis time for each chromatograph of 3.0
      min. The method has shown tremendous reproducibility with intra- and inter-day
      precision (coefficient of variation) <3.97 and 6.10%, respectively, and accuracy
      within +/-4.0% of nominal values. The validated method was applied to a
      pharmacokinetic study in human plasma samples generated after administration of a
      single oral dose of 2.0 mg dienogest tablets to healthy female volunteers and was
      proved to be highly reliable for the analysis of clinical samples.

PMID- 24890475
TI  - Writing a new story for Australia's children.

PMID- 24890476
TI  - Adult drinking in Australian schools.

PMID- 24890477
TI  - The impact of climate-related extreme events on public health workforce and
      infrastructure - how can we be better prepared?

PMID- 24890478
TI  - Twenty-eight day and one-year case fatality after hospitalisation with an acute
      coronary syndrome: a nationwide data linkage study.
AB  - OBJECTIVES: To determine 28-day and one-year case fatality in patients
      hospitalised with acute coronary syndromes (ACS) and identify factors associated
      with mortality. METHODS: All New Zealand residents admitted with ACS between 2007
      and 2009 were followed for one year using individual patient linkage of national
      hospitalisation and mortality datasets. Deaths from any cause were used to
      calculate 28-day and one-year case fatality. Cox-proportional hazards models were
      constructed to identify factors associated with mortality after an ACS
      hospitalisation. RESULTS: The cohort included 42,920 ACS patients. Case fatality
      increased steeply with age. Maori and Pacific peoples had 1.5 times the risk of
      28-day, and twice the risk of one-year, mortality as Europeans/Others. Low
      (compared to high) socioeconomic status was associated with significantly higher
      mortality at 28 days but not one year. Patients with unstable angina had half the
      risk of short-term mortality as NSTEMI patients, whereas STEMI patients had
      double the NSTEMI risk. CONCLUSIONS AND IMPLICATIONS: The major determinant of
      increasing case fatality was increasing age. There were also substantial
      differences in case fatality by ethnicity, deprivation and diagnostic category.
      Further research is needed to explore the possible mechanisms by which ethnic and
      deprivation disparities occur and effective strategies to address them.

PMID- 24890479
TI  - Geographic analysis of infant mortality in New Zealand, 1995-2008: an ethnicity
      perspective.
AB  - OBJECTIVE: To detect spatial clusters of high infant mortality rates in New
      Zealand for Maori and non-Maori populations and verify if these clusters are
      stable over a certain time period (1995-2008) and similar between the two
      populations. METHOD: We applied the Kulldorff's spatial scan statistics on data
      collected by New Zealand Ministry of Health (1995 to 2008) at the territorial
      local authorities (TLA) level. Kappa coefficient was used to assess the
      concordance between clusters obtained for Maori and non-Maori populations. T-test
      analyses were conducted to identify associations between spatial clusters and two
      predictors (population density and deprivation score). RESULTS: There are some
      significant spatial clusters of infant mortality in New Zealand for both Maori
      and Non-Maori. The concordance of the cluster locations between the two
      populations is strong (kappa=0.77). Unsurprisingly, infant mortality clusters for
      both Maori and Non-Maori are associated with the deprivation score. The
      population density predictor is only significantly and positively associated with
      clusters obtained for the non-Maori population. After controlling for deprivation
      the presence of spatial clusters is all but eliminated. CONCLUSIONS: Infant
      mortality patterns are geographically similar for both Maori and Non-Maori.
      However, there are differences geographically between the two populations after
      accounting for deprivation. IMPLICATIONS: Health services that can affect infant
      mortality should be aware of the geographical differences across NZ. Deprivation
      is an important factor in explaining infant mortality rates and policies that
      ameliorate its effects should be pursued, as it is the major determinant of the
      geographical pattern of infant mortality in NZ.

PMID- 24890480
TI  - Twelve-month post-injury outcomes for Maori and non-Maori: findings from a New
      Zealand cohort study.
AB  - OBJECTIVE: To examine the prevalence of key outcomes among Maori and non-Maori 12
      months post-injury, and to estimate the risk of these outcomes for Maori compared
      to non-Maori. METHODS: The Prospective Outcomes of Injury Study recruited 2,856
      New Zealand residents from five regions of New Zealand. This paper examines
      outcomes at 12 months post-injury for the Maori (n=405) and non-Maori (n=1,875)
      groups. RESULTS: High levels of adverse outcomes at 12 months post-injury were
      observed in both groups. A greater proportion of Maori than non-Maori were
      experiencing disability, problems with mobility and psychological distress 12
      months post-injury. After controlling for pre-injury and injury-related
      characteristics, Maori were found to be at greater risk of disability, problems
      with mobility, having trouble performing usual activities, psychological distress
      and reporting 'barely/not enough' household income at 12 months compared to non
      Maori. CONCLUSION: Explanations for higher risk of these poor outcomes are
      unclear. Future research to identify potential explanations will include
      experiences with health services and rehabilitation support following injury,
      subsequent injury and illness, and major life events post-injury. IMPLICATIONS:
      Adequate post-injury care focused on physical and psychological health and
      financial security is required to reduce the burden experienced by Maori due to
      injury.

PMID- 24890481
TI  - Remote school gardens: exploring a cost-effective and novel way to engage
      Australian Indigenous students in nutrition and health.
AB  - OBJECTIVE: This pilot study aimed to determine the feasibility of a novel, low
      cost program to get remote schools started in gardening and nutrition activities,
      for a lower cost than existing models, and without on-the-ground horticultural
      support. METHODS: A multi-site, mixed methods case study was undertaken, in which
      four remote schools were shipped gardening materials and a nutrition and cooking
      resource, and provided with horticultural support by phone and email. A support
      register and teacher surveys were used for four months of evaluation. RESULTS:
      The study demonstrated that the program is feasible, and may be associated with
      an increase from baseline in student's time spent cooking, gardening and on
      related classroom activities. CONCLUSIONS: The program was delivered economically
      without the need for on-the-ground staff, in a manner that was acceptable to
      teachers. IMPLICATIONS: This model may have application in remote schools
      throughout Australia, where there is a need to alter health impacting behaviours
      in high-risk populations. Lengthier program evaluation times and further resource
      development may be worth investigating in the future.

PMID- 24890482
TI  - High folate levels in Aboriginal children after subsidised fruit and vegetables
      and mandatory folic acid fortification.
AB  - OBJECTIVE: To evaluate the impact of a fruit and vegetable (F&V) subsidy program
      for disadvantaged Aboriginal children in Australia, implemented alongside the
      introduction of mandatory folic acid fortification of bread-making flour.
      METHODS: A before-and-after evaluation was undertaken of a F&V subsidy program at
      three Aboriginal community-controlled health services in New South Wales. The
      program provided a weekly box of subsidised F&V linked to preventive health
      services and nutrition promotion for families. In this analysis, red blood cell
      (RBC) folate was assessed together with self-reported dietary intake at baseline
      and 12 months later in a cohort of 125 children (aged 0-17 years). RESULTS: No
      children had low RBC folate at baseline or at follow-up; however, 33 children
      (26%) exceeded the reference range of RBC folate at baseline and 38 children
      (30%) exceeded the reference range at follow-up. Mean RBC folate levels increased
      substantially in children at follow-up (mean RBC folate z-score increased +0.55
      (95%CI 0.36-0.74). Change in F&V intake (p=0.196) and mean bread intake (p=0.676)
      were not statistically significant predictors for change in RBC folate levels.
      CONCLUSIONS: RBC folate levels increased among these disadvantaged Aboriginal
      children following mandatory folic acid fortification and participation in a
      subsidised F&V program. Even before mandatory folic acid fortification, none of
      these children had low RBC folate. IMPLICATIONS: The effect on health of
      mandatory fortification of foods with folate is not clear, hence, ongoing
      population-based monitoring of folate levels to assess the impact of mandatory
      folic acid fortification is important.

PMID- 24890483
TI  - Benefits of habit-based informational interventions: a randomised controlled
      trial of fruit and vegetable consumption.
AB  - OBJECTIVE: To assess the effectiveness of a habit-based intervention delivered by
      e-mail or sms in improving fruit and vegetable consumption among young adults.
      METHODS: An eight-week randomised controlled trial compared the effectiveness of
      three different types of message content (habit-based messages; food-group
      messages; general healthy eating messages) and two delivery methods (e-mail
      versus sms) on habit strength and consumption of fruits and vegetables in 71
      undergraduate participants. RESULTS: A significant message content by time
      interaction indicated that the habit-based intervention improved fruit
      consumption over the eight-week period. Vegetable consumption significantly
      increased over the intervention period regardless of message content. Delivery
      method did not influence these results. CONCLUSION: Messages based on a habit
      framework can be utilised to improve fruit consumption in young adults.
      Furthermore, simply reminding young adults to be conscious of their food choices
      may be sufficient to improve their overall vegetable consumption.

PMID- 24890484
TI  - Linking birth records to hospital admission records enhances the identification
      of women who smoke during pregnancy.
AB  - OBJECTIVE: Birth records and hospital admission records are valuable for research
      on maternal smoking, but individually are known to under-estimate smokers. This
      study investigated the extent to which combining data from these records enhances
      the identification of pregnant smokers, and whether this affects research
      findings such as estimates of maternal smoking prevalence and risk of adverse
      pregnancy outcomes associated with smoking. METHODS: A total of 846,039 birth
      records in New South Wales, Australia, (2001-2010) were linked to hospital
      admission records (delivery and antenatal). Algorithm 1 combined data from birth
      and delivery admission records, whereas algorithm 2 combined data from birth
      record, delivery and antenatal admission records. Associations between smoking
      and placental abruption, preterm birth, stillbirth, and low birthweight were
      assessed using multivariable logistic regression. RESULTS: Algorithm 1 identified
      127,612 smokers (smoking prevalence 15.1%), which was a 9.6% and 54.6% increase
      over the unenhanced identification from birth records alone (prevalence 13.8%),
      and delivery admission records alone (prevalence 9.8%), respectively. Algorithm 2
      identified a further 2,408 smokers from antenatal admission records. The
      enhancement varied by maternal socio-demographic characteristics (age, marital
      status, country of birth, socioeconomic status); obstetric factors (multi-fetal
      pregnancy, diabetes, hypertension); and maternity hospital. Enhanced and
      unenhanced identification methods yielded similar odds ratios for placental
      abruption, preterm birth, stillbirth and low birthweight. CONCLUSIONS: Use of
      linked data improved the identification of pregnant smokers. Studies relying on a
      single data source should adjust for the under-ascertainment of smokers among
      certain obstetric populations.

PMID- 24890485
TI  - Newspaper coverage of tobacco control in New Zealand.
AB  - OBJECTIVE: The New Zealand (NZ) government has proposed that the country be
      'Smokefree' by 2025. This paper examines how NZ newspapers have portrayed tobacco
      control initiatives to achieve this goal. METHOD: We examined tobacco-related
      articles from NZ newspapers published between 1 November 2011 and 31 October
      2012, using a coding frame to capture smoking themes, portrayal of actions and
      degree of support expressed for various pro- and anti- tobacco control
      objectives. RESULTS: A total of 537 separate articles were obtained from national
      and regional newspapers. Six themes appeared in more than 5% of the total
      articles: Smokefree 2025; smokefree areas; pricing; tobacco industry; plain
      packaging; and cessation. Overall, articles on tobacco smoking were three times
      more likely to emphasise actions consonant with tobacco control objectives rather
      than against them, and to report them with a positive rather than negative tone.
      CONCLUSIONS: NZ tobacco control advocates can take heart from the nature and
      extent of coverage of tobacco control initiatives. Opportunities for further
      media advocacy are discussed.

PMID- 24890486
TI  - Data linkage for injury surveillance and research in Australia: perils, pitfalls
      and potential.
AB  - OBJECTIVE: To outline some of the key issues for injury-related data linkage
      studies in Australia and describe potential applications of data linkage for
      injury surveillance and research. METHODS: Narrative review of data linkage
      capacity and injury-related data collection quality in Australia. RESULTS: The
      establishment of national and state-based data linkage centres in Australia has
      been a great leap forward for data linkage capacity for injury research. However,
      there are still limitations of using data linkage for injury surveillance and
      research. These are highlighted in the form of key perils and pitfalls, with
      examples provided. There is still much to be gained for injury research by using
      data linkage techniques to enhance the information available across the injury
      continuum, but data quality issues should always be acknowledged. CONCLUSIONS:
      Obtaining authorisation to link injury data collections for national research
      remains cumbersome. Streamlining of the application process is needed to ensure
      that injury research is able to be conducted in a timely fashion. Data quality
      and data linkage rates need to be considered when interpreting research findings.
      IMPLICATIONS: Streamlining of the application process for research that involves
      linking data collections would help ensure that research is conducted in a timely
      fashion.

PMID- 24890487
TI  - Suicide by occupational skill level in the Australian construction industry: data
      from 2001 to 2010.
AB  - OBJECTIVE: This study examines variation in suicide deaths by occupational skill
      level within the construction industry and changes in the rate of suicide over
      time. METHODS: Suicide deaths were extracted from a national coronial database
      and occupations were coded. Adjusted suicide rates over the period 2001 to 2010
      were calculated and incidence-rate ratios (IRRs) used to compare the overall
      burden of suicide in the lowest skilled group (machine operators and labourers)
      against skilled tradespersons in the construction industry. RESULTS: Those
      employed as labourers or machine operators had an adjusted rate of 18 per 100,000
      persons (95%CI 14-22) and those employed in skilled trades had an adjusted rate
      of 13 per 100,000 (95%CI 11-15) over the period 2001 to 2010. Compared to skilled
      trades, the lower skilled group had significantly elevated suicide at several
      time points over the period 2001 to 2010. The most observable difference in IRRs
      were in the years 2002 and 2007. CONCLUSIONS: Low-skilled workers in the
      construction industry had elevated rates of suicide compared to skilled trades
      workers. IMPLICATIONS: These workers should be targeted by prevention efforts.

PMID- 24890489
TI  - Population health services can influence land use planning.

PMID- 24890488
TI  - Using police crash databases for injury prevention research - a comparison of opt
      out and opt-in approaches to study recruitment.
AB  - OBJECTIVE: The study aimed to examine the difference in response rates between
      opt-out and opt-in participant recruitment in a population-based study of heavy
      vehicle drivers involved in a police-attended crash. METHODS: Two approaches to
      subject recruitment were implemented in two different states over a 14-week
      period and response rates for the two approaches (opt-out versus opt-in
      recruitment) were compared. RESULTS: Based on the eligible and contactable
      drivers, the response rates were 54% for the opt-out group and 16% for the opt-in
      group. CONCLUSIONS AND IMPLICATIONS: The opt-in recruitment strategy (which was a
      consequence of one jurisdiction's interpretation of the national Privacy Act at
      the time) resulted in an insufficient and potentially biased sample for the
      purposes of conducting research into risk factors for heavy-vehicle crashes.
      Australia's national Privacy Act 1988 has had a long history of inconsistent
      practices by state and territory government departments and ethical review
      committees. These inconsistencies can have profound effects on the validity of
      research, as shown through the significantly different response rates we reported
      in this study. It is hoped that a more unified interpretation of the Privacy Act
      across the states and territories, as proposed under the soon-to-be-released
      Australian Privacy Principles(1) will reduce the recruitment challenges outlined
      in this study.

PMID- 24890490
TI  - Standing meeting rooms - exploring enablers and barriers of interventions to
      reduce sitting time in the workplace.

PMID- 24890491
TI  - Christmas Island over 100 years: from beriberi to nutritional deficiencies of a
      different kind.

PMID- 24890492
TI  - Availability of chop-chop in Victorian tobacconists following introduction of
      plain packaging.

PMID- 24890496
TI  - Dynamic hydrolase activities precede hypersensitive tissue collapse in tomato
      seedlings.
AB  - Hydrolases such as subtilases, vacuolar processing enzymes (VPEs) and the
      proteasome play important roles during plant programmed cell death (PCD). We
      investigated hydrolase activities during PCD using activity-based protein
      profiling (ABPP), which displays the active proteome using probes that react
      covalently with the active site of proteins. We employed tomato (Solanum
      lycopersicum) seedlings undergoing synchronized hypersensitive cell death by co
      expressing the avirulence protein Avr4 from Cladosporium fulvum and the tomato
      resistance protein Cf-4. Cell death is blocked in seedlings grown at high
      temperature and humidity, and is synchronously induced by decreasing temperature
      and humidity. ABPP revealed that VPEs and the proteasome are not differentially
      active, but that activities of papain-like cysteine proteases and serine
      hydrolases, including Hsr203 and P69B, increase before hypersensitive tissue
      collapse, whereas the activity of a carboxypeptidase-like enzyme is reduced.
      Similar dynamics were observed for these enzymes in the apoplast of tomato
      challenged with C. fulvum. Unexpectedly, these challenged plants also displayed
      novel isoforms of secreted putative VPEs. In the absence of tissue collapse at
      high humidity, the hydrolase activity profile is already altered completely,
      demonstrating that changes in hydrolase activities precede hypersensitive tissue
      collapse. 

PMID- 24890498
TI  - Who's talking now? Infants' perception of vowels with infant vocal properties.
AB  - Little is known about infants' abilities to perceive and categorize their own
      speech sounds or vocalizations produced by other infants. In the present study,
      prebabbling infants were habituated to /i/ ("ee") or /a/ ("ah") vowels
      synthesized to simulate men, women, and children, and then were presented with
      new instances of the habituation vowel and a contrasting vowel on different
      trials, with all vowels simulating infant talkers. Infants showed greater
      recovery of interest to the contrasting vowel than to the habituation vowel,
      which demonstrates recognition of the habituation-vowel category when it was
      produced by an infant. A second experiment showed that encoding the vowel
      category and detecting the novel vowel required additional processing when infant
      vowels were included in the habituation set. Despite these added cognitive
      demands, infants demonstrated the ability to track vowel categories in a
      multitalker array that included infant talkers. These findings raise the
      possibility that young infants can categorize their own vocalizations, which has
      important implications for early vocal learning. 

PMID- 24890497
TI  - PBSC mobilization in lymphoma patients: analysis of risk factors for collection
      failure and development of a predictive score based on the kinetics of
      circulating CD34+ cells and WBC after chemotherapy and G-CSF mobilization.
AB  - Autologous stem cell transplantation (ASCT) is a potentially curative treatment
      of lymphoma, but peripheral blood stem cell (PBSC) mobilization fails in some
      patients. PBSC mobilizing agents have recently been proved to improve the PBSC
      yield after a prior mobilization failure. Predictive parameters of mobilization
      failure allowing for a preemptive, more cost-effective use of such agents during
      the first mobilization attempt are still poorly defined, particularly during
      mobilization with chemotherapy + granulocyte colony-stimulating factor (G-CSF).
      We performed a retrospective analysis of a series of lymphoma patients who were
      candidates for ASCT, to identify factors influencing PBSC mobilization outcome.
      Premobilization parameters-age, histology, disease status, mobilizing protocol,
      and previous treatments-as well as white blood cell (WBC) and PBSC kinetics,
      markers potentially able to predict failure during the ongoing mobilization
      attempt, were analyzed in 415 consecutive mobilization procedures in 388
      patients. We used chemotherapy + G-CSF in 411 (99%) of mobilization attempts and
      PBSC collection failed (<2 * 10(6) CD34+ PBSC/kg) in 13%. Multivariable analysis
      showed that only a low CD34+ PBSC count and CD34+ PBSC/WBC ratio, together with
      the use of nonplatinum-containing chemotherapy, independently predicted
      mobilization failure. Using these three parameters, we established a scoring
      system to predict risk of failure during mobilization ranging from 2 to 90%, thus
      allowing a selective use of a preemptive mobilization policy.

PMID- 24890499
TI  - The second shift reflected in the second generation: do parents' gender roles at
      home predict children's aspirations?
AB  - Gender inequality at home continues to constrain gender equality at work. How do
      the gender disparities in domestic labor that children observe between their
      parents predict those children's visions for their future roles? The present
      research examined how parents' behaviors and implicit associations concerning
      domestic roles, over and above their explicit beliefs, predict their children's
      future aspirations. Data from 326 children aged 7 to 13 years revealed that
      mothers' explicit beliefs about domestic gender roles predicted the beliefs held
      by their children. In addition, when fathers enacted or espoused a more
      egalitarian distribution of household labor, their daughters in particular
      expressed a greater interest in working outside the home and having a less
      stereotypical occupation. Fathers' implicit gender-role associations also
      uniquely predicted daughters' (but not sons') occupational preferences. These
      findings suggest that a more balanced division of household labor between parents
      might promote greater workforce equality in future generations. 

PMID- 24890500
TI  - Parental experiences with a hospital-based bead programme for children with
      congenital heart disease.
AB  - AIMS AND OBJECTIVES: To present survey findings on parental experiences with a
      hospital-based bead programme for children with congenital heart disease.
      BACKGROUND: The Heart Beads programme commenced at a paediatric hospital in
      Australia in 2008. Children enrolled in the programme are awarded a distinctive
      bead for every procedure/treatment they have while in hospital. A previous
      evaluation study on the programme revealed that the beads are therapeutic for the
      child and parents; however, due to a small sample size, the results were
      representative of the experiences of a small number of families who participated
      in the programme. DESIGN: This was an evaluation study which employed a
      nonexperimental descriptive design. METHODS: Surveys were mailed to all eligible
      families who enrolled in the programme. Data collection occurred between July
      December 2012. Questions on parental experiences with the Heart Beads programme
      were divided into three categories: understanding, acknowledgement and quality.
      Descriptive statistics were obtained and analysed. RESULTS/FINDINGS: One hundred
      and sixty-two mothers and 136 fathers responded to the survey. Heart Beads
      assisted mothers (83%) and fathers (80%) with understanding their child's
      condition and helped them with communication (mothers 80%, fathers 58%). The
      majority of fathers felt that their experience was acknowledged by nursing staff
      (64%) and medical staff (62%), while mothers indicated a higher response from
      nurses (76%) compared to medical staff (67%). Overall, parents rated the
      programme positively; however, there was some concern that children at times
      missed out on beads. CONCLUSION: Understanding how mothers and fathers experience
      the programme differently can guide staff in their communication with parents and
      inform future initiatives. RELEVANCE TO CLINICAL PRACTICE: The Heart Beads help
      nurses understand how parents are experiencing care and ways in which they can
      provide support and acknowledgement of the parent's experience.

PMID- 24890501
TI  - Effects of the bisphosphonate alendronate on molars of young rats after lateral
      luxation.
AB  - BACKGROUND AND AIM: The bisphosphonate alendronate (ALN) was employed with the
      aim of investigating its effects on dental and periodontal tissues after lateral
      luxation of developing molars. MATERIAL AND METHODS: Twenty-one-day-old Wistar
      rats had their second upper molars laterally luxated. Daily 2.5 mg kg(-1) ALN
      injections started at the day of the luxation; controls received sterile saline
      solution. The teeth were analyzed 7, 14, and 21 days after the procedure. On the
      days cited, the maxillae were fixed, decalcified, and embedded in paraffin or
      Spurr resin. The paraffin sections were stained with H&E, incubated for TRAP
      histochemistry or immunolabeled for osteopontin (OPN). Spurr ultrathin sections
      were examined in a transmission electron microscope. RESULTS: After 21 days, the
      root apex of luxated molars without ALN was wide open and disorganized and also
      covered by an irregular layer of cellular cementum, which was not observed in ALN
      treated animals. Ankylosis sites were observed in ALN rats in both luxated and
      non-luxated teeth. The TRAP-positive osteoclasts were more numerous in ALN group,
      despite their latent ultrastructural appearance without the presence of
      resorption apparatus compared to controls. OPN immunolabeling revealed a thick
      immunopositive line in the dentin that must be resultant from the moment of the
      luxation, while ALN-treated specimens did not present alterations in dentin.
      CONCLUSION: The present findings indicate that alendronate inhibits some
      alterations in dentin and cementum formation induced by dental trauma.

PMID- 24890502
TI  - A red-violaceous papular lesion in a young girl. Targetoid haemosiderotic
      haemangioma.

PMID- 24890503
TI  - Patient navigation moderates emotion and information demands of cancer treatment:
      a qualitative analysis.
AB  - PURPOSE: Patient navigation is increasingly employed to guide patients through
      cancer treatment. We assessed the elements of navigation that promoted patients'
      involvement in treatment among patients with breast and colorectal cancer that
      participated in a navigation study. METHODS: We conducted qualitative analysis of
      28 audiotaped and transcribed semi-structured interviews of navigated and
      unnavigated cancer patients. RESULTS: Themes included feeling emotionally and
      cognitively overwhelmed and desire for a strong patient-navigator partnership.
      Both participants who were navigated and those who were not felt that navigation
      did or could help address their emotional, informational, and communicational
      needs. The benefits of logistical support were cited less often. CONCLUSIONS:
      Findings underscore the salience of personal relationships between patients and
      navigators in meeting patients' emotional and informational needs.

PMID- 24890504
TI  - Phosphorus centers of different hybridization in phosphaalkene-substituted
      phospholes.
AB  - Phosphole-substituted phosphaalkenes (PPAs) of the general formula Mes*P=C(CH(3))
      (C(4)H(2)P(Ph))-R 5 a-c (Mes*=2,4,6-tBu(3)Ph; R=2-pyridyl (a), 2-thienyl (b),
      phenyl (c)) have been prepared from octa-1,7-diyne-substituted phosphaalkenes by
      utilizing the Fagan-Nugent route. The presence of two differently hybridized
      phosphorus centers (sigma(2) ,lambda(3) and sigma(3) ,lambda(3)) in 5 offers the
      possibility to selectively tune the HOMO-LUMO gap of the compounds by utilizing
      the different reactivity of the two phosphorus heteroatoms. Oxidation of 5 a-c by
      sulfur proceeds exclusively at the sigma(3) ,lambda(3) -phosphorus atom, thus
      giving rise to the corresponding thioxophospholes 6 a-c. Similarly, 5 a is
      selectively coordinated by AuCl at the sigma(3),lambda(3) -phosphorus atom.
      Subsequent second AuCl coordination at the sigma(2),lambda(3) -phosphorus
      heteroatom results in a dimetallic species that is characterized by a gold-gold
      interaction that provokes a change in pi conjugation. Spectroscopic,
      electrochemical, and theoretical investigations show that the phosphaalkene and
      the phosphole both have a sizable impact on the electronic properties of the
      compounds. The presence of the phosphaalkene unit induces a decrease of the HOMO
      LUMO gap relative to reference phosphole-containing pi systems that lack a P=C
      substituent.

PMID- 24890505
TI  - Role of autophagy and mTOR signaling in neural differentiation of bone marrow
      mesenchymal stem cells.
AB  - Autophagy is involved in cell differentiation. We present evidence that autophagy
      is activated during beta-mercaptoethanol (beta-ME)-induced neuronal
      differentiation of bone marrow mesenchymal stem cells (MSCs), in which mammalian
      target of rapamycin (mTOR) signaling is important. mTOR activity declined after
      being transported from the nucleus to the cytoplasm. Using 3-methyladenine (3-MA)
      and rapamycin to regulate the activity of mTOR, it was found that the efficiency
      of neuronal differentiation was affected. 

PMID- 24890506
TI  - The impact of change in pregnancy body mass index on macrosomia.
AB  - OBJECTIVE: To examine the impact of change in body mass index (BMI) during
      pregnancy on the incidence of macrosomia. METHODS: This is a retrospective cohort
      study using 2007 linked birth certificate and discharge diagnosis data from the
      state of California. Adjusted odds ratios (aOR) with 95% confidence intervals
      (CI) were calculated for the outcome of macrosomia, as a function of a
      categorical change in pregnancy BMI: BMI loss (<-0.5), no change (-0.5 to 0.5),
      minimal (0.6 to 5), moderate (5.1 to 10), and excessive (>10). The impact of
      pregnancy change in BMI was determined for the entire cohort and then stratified
      by prepregnancy BMI category. Minimal BMI change served as the reference group.
      RESULTS: The study population consisted of 436,414 women. Overall, women with
      moderate and excessive BMI changes had aORs of 1.66 and 3.21, respectively, for
      macrosomia, when compared with women with minimal BMI change. When stratified by
      prepregnancy BMI, normal (aOR 3.85) and overweight women (aOR 2.96) with
      antenatal BMI change greater than 10 had the highest odds of macrosomia.
      CONCLUSIONS: Excessive change in pregnancy BMI results in an increased odds of
      macrosomia. This finding was most pronounced in the normal and overweight women.

PMID- 24890507
TI  - A fluorescent organic light-emitting diode with 30% external quantum efficiency.
AB  - Almost 100% internal quantum efficiency (IQE) is achieved with a green
      fluorescent organic light-emitting diode (OLED) exhibiting 30% external quantum
      efficiency (EQE). The OLED comprises an exciplex-forming co-host system doped
      with a fluorescent dye that has a strong delayed fluorescence as a result of
      reverse intersystem crossing (RISC); the exciplex-forming co-hosts stimulate
      energy transfer and charge balance in the system. The orientation of the
      transition dipole moment of the fluorescent dye is shown to have an influence on
      the EQE of the device. 

PMID- 24890508
TI  - How natural a kind is "eukaryote?".
AB  - Systematics balances uneasily between realism and nominalism, uncommitted as to
      whether biological taxa are discoveries or inventions. If the former, they might
      be taken as natural kinds. I briefly review some philosophers' concepts of
      natural kinds and then argue that several of these apply well enough to
      "eukaryote." Although there are some sticky issues around genomic chimerism and
      when eukaryotes first appeared, if we allow for degrees in the naturalness of
      kinds, existing eukaryotes rank highly, higher than prokaryotes. Most biologists
      feel this intuitively: All I attempt to do here is provide some conceptual
      justification.

PMID- 24890510
TI  - DNA degradation and its defects.
AB  - DNA is one of the most essential molecules in organisms, containing all the
      information necessary for organisms to live. It replicates and provides a
      mechanism for heredity and evolution. Various events cause the degradation of DNA
      into nucleotides. DNA also has a darker side that has only recently been
      recognized; DNA that is not properly degraded causes various diseases. In this
      review, we discuss four deoxyribonucleases that function in the nucleus, cytosol,
      and lysosomes, and how undigested DNA causes such diseases as cancer, cataract,
      and autoinflammation. Studies on the biochemical and physiological functions of
      deoxyribonucleases should continue to increase our understanding of cellular
      functions and human diseases.

PMID- 24890512
TI  - Pharmacological inhibition of bromodomain-containing proteins in inflammation.
AB  - Inflammation is associated with the activation of genes that contribute to immune
      defense and tissue repair. The bromodomain-containing proteins of the BET family,
      which recognize histone lysine acetylation, play a key role in the
      transcriptional control of inflammatory genes. Inhibition of BET proteins by the
      small-molecule inhibitor I-BET affects the expression of a particular subset of
      inflammatory genes-namely, ones that follow an "analog-like," but not "digital
      like" activation pattern. This ability of I-BET to target genes based on the
      dynamic pattern of their activation may facilitate the further development of
      anti-inflammatory treatment protocols that are tuned to the individual or to
      disease-specific patterns of gene expression.

PMID- 24890509
TI  - Origin of spliceosomal introns and alternative splicing.
AB  - In this work we review the current knowledge on the prehistory, origins, and
      evolution of spliceosomal introns. First, we briefly outline the major features
      of the different types of introns, with particular emphasis on the
      nonspliceosomal self-splicing group II introns, which are widely thought to be
      the ancestors of spliceosomal introns. Next, we discuss the main scenarios
      proposed for the origin and proliferation of spliceosomal introns, an event
      intimately linked to eukaryogenesis. We then summarize the evidence that suggests
      that the last eukaryotic common ancestor (LECA) had remarkably high intron
      densities and many associated characteristics resembling modern intron-rich
      genomes. From this intron-rich LECA, the different eukaryotic lineages have taken
      very distinct evolutionary paths leading to profoundly diverged modern genome
      structures. Finally, we discuss the origins of alternative splicing and the
      qualitative differences in alternative splicing forms and functions across
      lineages.

PMID- 24890511
TI  - Clathrin-independent pathways of endocytosis.
AB  - There are many pathways of endocytosis at the cell surface that apparently
      operate at the same time. With the advent of new molecular genetic and imaging
      tools, an understanding of the different ways by which a cell may endocytose
      cargo is increasing by leaps and bounds. In this review we explore pathways of
      endocytosis that occur in the absence of clathrin. These are referred to as
      clathrin-independent endocytosis (CIE). Here we primarily focus on those pathways
      that function at the small scale in which some have distinct coats (caveolae) and
      others function in the absence of specific coated intermediates. We follow the
      trafficking itineraries of the material endocytosed by these pathways and finally
      discuss the functional roles that these pathways play in cell and tissue
      physiology. It is likely that these pathways will play key roles in the
      regulation of plasma membrane area and tension and also control the availability
      of membrane during cell migration.

PMID- 24890513
TI  - Epigenetic control of immunity.
AB  - Immunity relies on the heterogeneity of immune cells and their ability to respond
      to pathogen challenges. In the adaptive immune system, lymphocytes display a
      highly diverse antigen receptor repertoire that matches the vast diversity of
      pathogens. In the innate immune system, the cell's heterogeneity and phenotypic
      plasticity enable flexible responses to changes in tissue homeostasis caused by
      infection or damage. The immune responses are calibrated by the graded activity
      of immune cells that can vary from yeast-like proliferation to lifetime dormancy.
      This article describes key epigenetic processes that contribute to the function
      of immune cells during health and disease.

PMID- 24890515
TI  - Detection of inheritance pattern in thirty-three Mexican males with chronic
      granulomatous disease through 123 dihydrorhodamine assay.
AB  - BACKGROUND: There are two inheritance patterns, the X-linked recessive (XL)
      pattern and the autosomal recessive pattern. There is no information on the
      predominant inheritance pattern of male patients with chronic granulomatous
      disease (CGD) in Mexico. OBJECTIVE: The aim of this study was to determine the
      inheritance pattern in a cohort of Mexican male patients with CGD by means of the
      detection of an XL status carrier among their female relatives, and to describe
      the frequency of discoid lupus (DL) among carriers. METHODS: We detected the
      female relatives within the families of male patients with CGD, and carried out
      the 123 dihydrorhodamine (DHR) assay in all female participants. All carriers
      were questioned for current or past established DL diagnosis. RESULTS: We
      detected 33 families with one or more CGD male patients; we found an XL-CGD in
      79% of the relatives from at least one female relative with a bimodal pattern.
      For the remaining seven relatives we were not able to confirm a carrier status by
      means of a DHR assay. Moreover, we detected one mother with CGD secondary to
      skewed X-chromosome inactivation. We also found 47 carriers, and only one carrier
      with DL among them. CONCLUSION: We concluded that XL-CGD is the most frequent
      form of CGD in a cohort of CGD male patients in Mexico. DHR assay is a fast and
      practical tool to determine the CGD form in the Latin-American countries.
      Finally, DL frequency in Mexico is lower than that reported in the literature for
      other regions of the world.

PMID- 24890516
TI  - Simple sequence repeats in the national longitudinal study of adolescent health:
      an ethnically diverse resource for genetic analysis of health and behavior.
AB  - Simple sequence repeats (SSRs) are one of the earliest available forms of genetic
      variation available for analysis and have been utilized in studies of
      neurological, behavioral, and health phenotypes. Although findings from these
      studies have been suggestive, their interpretation has been complicated by a
      variety of factors including, among others, limited power due to small sample
      sizes. The current report details the availability, diversity, and allele and
      genotype frequencies of six commonly examined SSRs in the ethnically diverse,
      population-based National Longitudinal Study of Adolescent Health. A total of
      106,743 genotypes were generated across 15,140 participants that included four
      microsatellites and two di-nucleotide repeats in three dopamine genes (DAT1,
      DRD4, DRD5), the serotonin transporter, and monoamine oxidase A. Allele and
      genotype frequencies showed a complex pattern and differed significantly between
      populations. For both di-nucleotide repeats we observed a greater allelic
      diversity than previously reported. The availability of these six SSRs in a
      large, ethnically diverse sample with extensive environmental measures assessed
      longitudinally offers a unique resource for researchers interested in health and
      behavior. 

PMID- 24890518
TI  - Treatment of nodular facial angiofibromas in tuberous sclerosis, using ultrapulse
      carbon dioxide laser.
AB  - Tuberous sclerosis (TS) is a genodermatosis characterized by facial angiofibromas
      (FAs). These tumours cause aesthetic disfigurement and obstruction of vision, and
      haemorrhage when traumatized, which can lead to emotional distress and
      relationship difficulties. We report the case of a 35-year-old patient with
      extensive TS-associated FAs that were treated with an ultrapulse carbon dioxide
      laser (UPCDL). UPCDL laser seems to be a easy, useful and convenient tool for the
      treatment of nodular FAs, which provides good aesthetic results, and a positive
      response from patients, who report high levels of satisfaction with the results.
      Minimal recurrence of the tumours occurred during long-term follow-up, and these
      were successfully treated with UPCDL. It is not yet possible to correct the
      genetic alterations underlying TS, but UPCDL treatment is a convenient tool to
      improve the facial appearance of patients with severe FAs. 

PMID- 24890514
TI  - CSF-1 receptor signaling in myeloid cells.
AB  - The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony
      stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles
      in development and in innate immunity by regulating the development of most
      tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth
      cells of the small intestine, and of brain microglia. It also regulates the
      differentiation of neural progenitor cells and controls functions of oocytes and
      trophoblastic cells in the female reproductive tract. Owing to this broad tissue
      expression pattern, it plays a central role in neoplastic, inflammatory, and
      neurological diseases. In this review we summarize the evolution, structure, and
      regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1,
      IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of
      the receptor. We further describe the pathways regulating macrophage survival,
      proliferation, differentiation, and chemotaxis downstream from the CSF-1R.

PMID- 24890517
TI  - Can performance on daily activities discriminate between older adults with normal
      cognitive function and those with mild cognitive impairment?
AB  - OBJECTIVES: To examine whether preclinical disability in performance of
      cognitively focused instrumental activity of daily living (C-IADL) tasks can
      discriminate between older adults with normal cognitive function and those with
      mild cognitive impairment (MCI) and, secondarily, to determine the two tasks with
      the strongest psychometric properties and assess their discriminative ability so
      as to generate diagnosis-relevant information about cognitive changes associated
      with MCI and mild neurocognitive disorder according to Diagnostic and Statistical
      Manual of Mental Disorders, Fifth Edition, criteria. DESIGN: Secondary analyses
      of cross-sectional data from a cohort of individuals diagnosed with normal
      cognitive function or MCI. SETTING: Pittsburgh, Pennsylvania. PARTICIPANTS: Older
      adults with remitted major depression (N = 157). MEASUREMENTS: Diagnosis of
      cognitive status was made at the Alzheimer's Disease Research Center, University
      of Pittsburgh. Performance on eight C-IADLs was measured using the criterion
      referenced, observation-based Performance Assessment of Self-Care Skills (PASS).
      RESULTS: Ninety-six older adults with normal cognitive function (mean age 72.5 +/
      5.9) and 61 with MCI (mean age 75.5 +/- 6.3) participated. The eight C-IADLs
      demonstrated 81% accuracy in discriminating cognitive status (area under the
      receiver operating characteristic curve (AUC) = 0.81, P < .001). Two tasks
      (shopping and checkbook balancing) were the most discriminating (AUC = 0.80, P <
      .001); they demonstrated similar ability as all eight C-IADLs in determining
      cognitive status. Assessing performance on these two C-IADLs takes 10 to 15
      minutes. CONCLUSION: This is the first demonstration of the discriminative
      ability of preclinical disability to distinguish older adults with MCI from
      cognitively normal older adults. These findings highlight potential tasks that,
      when measured using the observation-based PASS, demonstrate greater effort for
      individuals with MCI. These tasks may be considered when attempting to diagnose
      MCI or mild neurocognitive disorder in clinical practice and research.

PMID- 24890520
TI  - Aspirin intake and breast cancer survival - a nation-wide study using
      prospectively recorded data in Sweden.
AB  - BACKGROUND: Aspirin (ASA) use has been associated with improved breast cancer
      survival in several prospective studies. METHODS: We conducted a nested case
      control study of ASA use after a breast cancer diagnosis among women using
      Swedish National Registries. We assessed prospectively recorded ASA exposure
      during several different time windows following cancer diagnosis using
      conditional logistic regression with breast cancer death as the main outcome.
      Within each six-month period of follow-up, we categorized dispensed ASA doses
      into three groups: 0, less than 1, and 1 or more daily doses. RESULTS: We
      included 27,426 women diagnosed with breast cancer between 2005 and 2009; 1,661
      died of breast cancer when followed until Dec 31, 2010. There was no association
      between ASA use and breast cancer death when exposure was assessed either shortly
      after diagnosis, or 3-12 months before the end of follow-up. Only during the
      period 0-6 months before the end of follow-up was ASA use at least daily compared
      with non-use associated with a decreased risk of breast cancer death: HR (95% CI)
      =0.69 (0.56-0.86). However, in the same time-frame, those using ASA less than
      daily had an increased risk of breast cancer death: HR (95% CI) =1.43 (1.09
      1.87). CONCLUSIONS: Contrary to other studies, we did not find that ASA use was
      associated with a lower risk of death from breast cancer, except when assessed
      short term with no delay to death/end of follow-up, which may reflect
      discontinuation of ASA during terminal illness.

PMID- 24890519
TI  - Th17 cells and interleukin-17 increase with poor prognosis in patients with acute
      myeloid leukemia.
AB  - Although Th17 cells play crucial roles in the pathogenesis of many autoimmune and
      inflammatory disorders, their roles in malignancies are currently under debate.
      The role and mechanism of Th17 cells in patients with acute myeloid leukemia
      (AML) remain poorly understood. Here we demonstrated that the frequency of Th17
      cells was significantly increased in peripheral blood mononuclear cells (PBMCs)
      and bone marrow mononuclear cells from AML patients compared with healthy donors.
      Plasma levels of interleukin (IL)-17, IL-22, IL-23, IL-1beta, IL-6, and
      transforming growth factor (TGF)-beta1 were significantly increased in blood and
      bone marrow in AML patients compared with healthy donors. The in vitro
      experiments demonstrated that IL-1beta, IL-6, IL-23, but not TGF-beta1 promoted
      the generation and differentiation of Th17 cells from naive CD4(+) T cells in
      humans. IL-17A, a signature cytokine secreted by Th17 cells, induced the
      proliferation of IL-17 receptor (IL-17R)-positive AML cells via IL-17R, in which
      activation of PI3K/Akt and Jak/Stat3 signaling pathway may play important roles.
      In addition, combination of IL-17A and IL-22 significantly reduced the generation
      of Th1 cells and the production of interferon (IFN)-gamma from healthy donor or
      AML patient peripheral blood mononuclear cells. Patients with high Th17 cell
      frequency had poor prognosis, whereas patients with high Th1 cell frequency had
      prolonged survival. Combined analysis of Th1 and Th17 cell frequencies improved
      the ability to predict patient outcomes. In conclusion, Th17 cells play a crucial
      role in the pathogenesis of AML and may be an important therapeutic target and
      prognostic predictor. 

PMID- 24890521
TI  - Can the cold pressor test predict future cardiovascular events in patients
      without demonstrated ischemic heart disease by SPECT?
AB  - OBJECTIVE: To assess whether a cold pressor test (CPT) could help identify
      patients at a high risk of cardiovascular events in a population without known
      coronary artery disease (CAD) with a normal myocardial perfusion scintigraphy
      (MPS). METHODS: Our population consisted of 870 patients with a mean age of
      59.3years with several CAD risk factors, having been referred for an MPS. The CPT
      was performed between the third day and fifth day after the MPS. RESULTS: The CPT
      was positive in 38.2% of the patients. After a mean 40-month follow-up, the
      patients were contacted to check for cardiac death, non-fatal myocardial
      infarction, and myocardial revascularization procedures. The event-free survival
      rates were 98.1% and 90.4% after a negative or positive CPT, respectively
      (p=0.0001). The positive CPT group exhibited a fourfold increased risk of CV
      events. All CV events in the negative CPT group occurred after a 30-month follow
      up. The risk of CV events was 4.5 times higher in diabetic patients. CONCLUSION:
      A positive CPT in patients with a negative MPS could help identify a subgroup of
      patients at a higher risk of developing symptomatic CAD. PRACTICE IMPLICATIONS:
      Our results suggest that after a normal post-exercise MPS, patients should
      undergo a CPT.

PMID- 24890523
TI  - Targeted therapies in cancer and mechanisms of resistance.

PMID- 24890522
TI  - Reduced levels of maternal progesterone during pregnancy increase the risk for
      allergic airway diseases in females only.
AB  - Observational as well as experimental studies support that prenatal challenges
      seemed to be associated with an increased risk for allergic airway diseases in
      the offspring. However, insights into biomarkers involved in mediating this risk
      are largely elusive. We here aimed to test the association between endogenous and
      exogenous factors documented in pregnant women, including psychosocial,
      endocrine, and life style parameters, and the risk for allergic airway diseases
      in the children later in life. We further pursued to functionally test identified
      factors in a mouse model of an allergic airway response. In a prospectively
      designed pregnancy cohort (n = 409 families), women were recruited between the
      4th and 12th week of pregnancy. To investigate an association between exposures
      during pregnancy and the incidence of allergic airway disease in children between
      3 and 5 years of age, multiple logistic regression analyses were applied.
      Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female
      mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In
      addition to the prenatal stress challenge, some pregnant females were treated
      with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we
      observed that high levels of maternal progesterone in early human pregnancies
      were associated with a decreased risk for an allergic airway disease (asthma or
      allergic rhinitis) in daughters (adjusted OR 0.92; 95% confidence interval [CI]
      0.84 to 1.00) but not sons (aOR 1.02, 95% CI 0.94-1.10). In mice, prenatal DHD
      supplementation of stress-challenged dams attenuated prenatal stress-induced
      airway hyperresponsiveness exclusively in female offspring. Reduced levels of
      maternal progesterone during pregnancy-which can result from high stress
      perception-increase the risk for allergic airway diseases in females but not in
      males. Key messages: Lower maternal progesterone during pregnancy increases the
      risk for allergic airway disease only in female offspring. Prenatal progesterone
      supplementation ameliorates airway hyperreactivity in prenatally stressed murine
      offspring.

PMID- 24890524
TI  - Iterative assembly of two separate polyketide chains by the same single-module
      bacterial polyketide synthase in the biosynthesis of HSAF.
AB  - Antifungal HSAF (heat-stable antifungal factor, dihydromaltophilin) is a
      polycyclic tetramate macrolactam from the biocontrol agent Lysobacter
      enzymogenes. Its biosynthetic gene cluster contains only a single-module
      polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS), although two
      separate hexaketide chains are required to assemble the skeleton. To address the
      unusual biosynthetic mechanism, we expressed the biosynthetic genes in two
      "clean" strains of Streptomyces and showed the production of HSAF analogues and a
      polyene tetramate intermediate. We then expressed the PKS module in Escherichia
      coli and purified the enzyme. Upon incubation of the enzyme with acyl-coenzyme A
      and reduced nicotinamide adenine dinucleotide phosphate (NADPH), a polyene was
      detected in the tryptic acyl carrier protein (ACP). Finally, we incubated the
      polyene-PKS with the NRPS module in the presence of ornithine and adenosine
      triphosphate (ATP), and we detected the same polyene tetramate as that in
      Streptomyces transformed with the PKS-NRPS alone. Together, our results provide
      evidence for an unusual iterative biosynthetic mechanism for bacterial polyketide
      peptide natural products. 

PMID- 24890525
TI  - Proceedings from Duke resistant hypertension think tank.
AB  - To identify patients at increased risk for cardiovascular outcomes, apparent
      treatment resistant hypertension (aTRH) is defined as having a blood pressure
      (BP) above goal despite the use of >=3 antihypertensive therapies of different
      classes at maximally tolerated doses, ideally including a diuretic. In light of
      growing scientific interest in the treatment of this group, a multistakeholder
      think tank was convened to discuss the current state of knowledge, improve the
      care of these patients, and identify appropriate study populations for future
      observational and randomized trials in the field. Although recent epidemiologic
      studies in selected populations estimate that the prevalence of aTRH is 10% to
      15% of hypertensive patients, further large-scale observational studies will be
      needed to better elucidate risk factors. To spur the development of therapies for
      aTRH, the development of an "aTRH" label for pharmacologic and device therapies
      with a developmental pathway including treatment added to the use of existing
      therapies is favored. Although demonstration of adequate BP lowering should be
      sufficient to gain Food and Drug Administration approval for therapies targeting
      aTRH, assessment of improvement in quality of life and cardiovascular outcomes is
      also desirable and considered in Centers for Medicare and Medicaid Services
      coverage decisions. Device trials under the aTRH label will need uniform and
      consistent processes for defining appropriate patient populations as well as
      postapproval registries assessing both long-term safety and duration of
      responses. Finally, patients with aTRH are likely to benefit from evaluation by a
      hypertension team to assure proper patient identification, diagnostic work-up,
      and therapeutic management before consideration of advanced or novel therapies to
      lower BP. 

PMID- 24890526
TI  - Carcinoid heart disease: current understanding and future directions.
AB  - Carcinoid tumors are rare and aggressive malignancies. A multitude of vasoactive
      agents are central to the systemic effects of these tumors. The additional burden
      of cardiac dysfunction heralds a steep decline in quality of life and survival.
      Unfortunately, by the time carcinoid syndrome surfaces clinically, the likelihood
      of cardiac involvement is 50%. Although medical therapies such as somatostatin
      analogues may provide some symptom relief, they offer no mortality benefit. On
      the other hand, referral to surgery following early detection has shown increased
      survival. The prompt recognition of this disease is therefore of the utmost
      importance. 

PMID- 24890528
TI  - Rationale and design of the PeriOperative ISchemic Evaluation-2 (POISE-2) trial:
      an international 2 * 2 factorial randomized controlled trial of acetyl-salicylic
      acid vs. placebo and clonidine vs. placebo in patients undergoing noncardiac
      surgery.
AB  - BACKGROUND: Worldwide, 200 million adults undergo major noncardiac surgery
      annually, and 10 million of these patients will have a major vascular
      complication. Low-dose clonidine and low-dose acetyl-salicylic acid (ASA) may
      prevent major perioperative vascular complications. We therefore initiated the
      POISE-2 trial to establish the perioperative effects of these 2 interventions.
      METHODS: The POISE-2 trial is a 2 * 2 factorial randomized controlled trial of
      low-dose ASA vs. placebo and low-dose clonidine vs. placebo in 10,000 patients at
      risk for a perioperative cardiovascular event who are undergoing noncardiac
      surgery. Both study drugs are initiated prior to surgery (goal 2-4 hours) and are
      continued after surgery. Patients, health care providers, data collectors, and
      outcome adjudicators are blinded to treatment allocation. The primary outcome is
      a composite of mortality and nonfatal myocardial infarction at 30 days after
      randomization. RESULTS: To date, the POISE-2 trial has recruited more than 9,000
      patients from 135 centers in 23 countries. Among the first 7,500 patients
      recruited, patients' mean age was 68.2 years, 53.4% were male, 34.0% had a
      history of vascular disease, and 38.3% had diabetes that was treated.
      Participants had orthopedic (38.1%), general (27.0%), urologic or gynecologic
      (17.2%), vascular (6.6%), thoracic (5.7%), and other (5.4%) surgery. CONCLUSIONS:
      POISE-2 is a large international trial that will rigorously evaluate the effects
      of low-dose clonidine and ASA in patients having noncardiac surgery.

PMID- 24890527
TI  - PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and
      design of the PROMISE trial.
AB  - BACKGROUND: Suspected coronary artery disease (CAD) is one of the most common,
      potentially life-threatening diagnostic problems clinicians encounter. However,
      no large outcome-based randomized trials have been performed to guide the
      selection of diagnostic strategies for these patients. METHODS: The PROMISE study
      is a prospective, randomized trial comparing the effectiveness of 2 initial
      diagnostic strategies in patients with symptoms suspicious for CAD. Patients are
      randomized to either (1) functional testing (exercise electrocardiogram, stress
      nuclear imaging, or stress echocardiogram) or (2) anatomical testing with >=64
      slice multidetector coronary computed tomographic angiography. Tests are
      interpreted locally in real time by subspecialty certified physicians, and all
      subsequent care decisions are made by the clinical care team. Sites are provided
      results of central core laboratory quality and completeness assessment. All
      subjects are followed up for >=1 year. The primary end point is the time to
      occurrence of the composite of death, myocardial infarction, major procedural
      complications (stroke, major bleeding, anaphylaxis, and renal failure), or
      hospitalization for unstable angina. RESULTS: More than 10,000 symptomatic
      subjects were randomized in 3.2 years at 193 US and Canadian cardiology,
      radiology, primary care, urgent care, and anesthesiology sites. CONCLUSION:
      Multispecialty community practice enrollment into a large pragmatic trial of
      diagnostic testing strategies is both feasible and efficient. The PROMISE trial
      will compare the clinical effectiveness of an initial strategy of functional
      testing against an initial strategy of anatomical testing in symptomatic patients
      with suspected CAD. Quality of life, resource use, cost-effectiveness, and
      radiation exposure will be assessed.

PMID- 24890530
TI  - Posttreatment platelet reactivity on clopidogrel is associated with the risk of
      adverse events after off-pump coronary artery bypass.
AB  - BACKGROUND: Dual antiplatelet therapy with aspirin and clopidogrel is currently
      recommended in off-pump coronary artery bypass (OPCAB). However, no data exist
      concerning platelet reactivity on clopidogrel after OPCAB. The aim of this study
      was to assess the relationship between platelet reactivity and late major adverse
      cardiovascular events (MACEs) after OPCAB. METHODS: In this prospective, single
      center, observational study, on-clopidogrel platelet reactivity was measured
      using a point-of-care assay (VerifyNow system; Accumetrics Inc, San Diego, CA) in
      859 patients who underwent OPCAB with 1 or more vein grafts. The primary end
      point was late MACEs (30 days-1 year) including cardiac death, nonfatal
      myocardial infarction, and target vessel revascularization. Receiver operating
      characteristic curve analysis was used to estimate the cutoff value of P2Y12
      reaction units (PRUs) for MACEs. RESULTS: The optimal cutoff value for
      posttreatment reactivity for the incidence of late MACEs was >=188 PRU (area
      under the curve 0.72, 95% CI 0.68-0.75, P = .002). The incidence of late MACEs
      was significantly higher in the high platelet reactivity (HPR; >=188 PRU) group
      than in the low platelet reactivity (<188 PRU) group (3.6% vs. 1.4%, P = .040).
      Kaplan-Meier analysis revealed 1-year MACE-free survival rates of 98.4% +/- 0.5%
      and 95.9% +/- 1.3% in the low platelet reactivity and HPR groups, respectively (P
      = .034). According to a Cox regression hazard model, HPR was an independent risk
      factor for late MACE-free survival (hazard ratio 3.51, 95% CI 1.27-9.69, P =
      .015). CONCLUSION: High residual platelet reactivity after clopidogrel
      administration is strongly associated with 1-year MACE-free survival. Routine
      measurement of platelet reactivity and thorough monitoring of patients with HPR
      after OPCAB are warranted.

PMID- 24890529
TI  - Adherence to dabigatran therapy and longitudinal patient outcomes: insights from
      the veterans health administration.
AB  - BACKGROUND: Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of
      stroke in patients with non-valvular atrial fibrillation (NVAF). It does not
      require routine monitoring with laboratory testing which may have an adverse
      impact on adherence. We aimed to describe adherence to dabigatran in the first
      year after initiation and assess the association between non-adherence to
      dabigatran and clinical outcomes in a large integrated healthcare system.
      METHODS: We studied a national cohort of 5,376 patients with NVAF, initiated on
      dabigatran between October-2010 and September-2012 at all Veterans Affairs
      hospitals. Adherence to dabigatran was calculated as proportion of days covered
      (PDC) and association between PDC and outcomes was assessed using standard
      regression techniques. RESULTS: Mean age of the study cohort was 71.3 +/- 9.7
      years; 98.3% were men and mean CHADS2 score was 2.4 +/- 1.2 (mean CHA2DS2VASc
      score 3.2 +/- 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% +/- 22%) over
      a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients
      had a PDC <80% and were classified as non-adherent. After multivariable
      adjustment, lower adherence was associated with increased risk for combined all
      cause mortality and stroke (HR 1.13, 95% CI 1.07-1.19 per 10% decrease in PDC).
      Adherence to dabigatran was not associated with non-fatal bleeding or myocardial
      infarction. CONCLUSIONS: In the year after initiation, adherence to dabigatran
      for a majority of patients is very good. However, 28% of patients in our cohort
      had poor adherence. Furthermore, lower adherence to dabigatran was associated
      with increased adverse outcomes. Concerted efforts are needed to optimize
      adherence to NOACs.

PMID- 24890532
TI  - The quality of antiplatelet and anticoagulant medication administration among ST
      segment elevation myocardial infarction patients transferred for primary
      percutaneous coronary intervention.
AB  - BACKGROUND: Timely and appropriate use of antiplatelet and anticoagulant
      therapies has been shown to improve outcomes among ST-segment elevation
      myocardial infarction (STEMI) patients but has not been well described in
      patients transferred for primary percutaneous coronary intervention (PCI).
      METHODS: We examined 16,801 (26%) transfer and 47,329 direct-arrival STEMI
      patients treated with primary PCI at 441 Acute Coronary Treatment and
      Intervention Outcomes Network Registry-Get With The Guidelines hospitals.
      Medication use was compared between transfer and direct-arrival patients to
      determine if these therapies were delayed or dosed in excess. RESULTS: Although
      transfer patients were more likely to receive antiplatelet and anticoagulant
      therapies before catheterization, they had longer delays to initiation of heparin
      (35 vs. 25 minutes), clopidogrel (119 vs. 84 minutes), and glycoprotein IIb/IIIa
      inhibitor (107 vs. 60 minutes, P < .0001 for both). Administration of low
      molecular-weight heparin and glycoprotein IIb/IIIa inhibitor at the STEMI
      referring hospital was associated with longer delays to reperfusion compared with
      deferred administration at the STEMI-receiving hospital, whereas early use of
      unfractionated heparin was not. Among treated patients, those transferred were
      more likely to receive excess heparin dosing (adjusted odds ratio [OR] 1.28 [95%
      CI 1.04-1.58] for unfractionated heparin, adjusted OR 1.54 [95% CI 1.09-2.18] for
      low-molecular-weight heparin) and are associated with higher risks of major
      bleeding complications (adjusted OR 1.10, 95% CI 1.03-1.17). CONCLUSIONS: ST
      segment elevation myocardial infarction patients transferred for primary PCI in
      community practice are at risk for delayed and excessively dosed antithrombotic
      therapy, highlighting the need for continued quality improvement to maximize the
      appropriate use of these important adjunctive therapies.

PMID- 24890531
TI  - Aldosterone inhibition and coronary endothelial function in women without
      obstructive coronary artery disease: an ancillary study of the national heart,
      lung, and blood institute-sponsored women's ischemia syndrome evaluation.
AB  - Endothelial dysfunction is highly prevalent and associated with adverse outcomes
      among patients without obstructive coronary artery disease (CAD). Angiotensin II
      inhibition may improve endothelial function, but with continued treatment,
      "aldosterone escape" may occur. Thus, it is unknown if adding aldosterone
      blockade further improves endothelial function. METHODS: In a double-blind,
      parallel-group, repeated-measures study, women with symptoms and signs of
      ischemia, no significant CAD, and coronary endothelial dysfunction receiving an
      angiotensin-converting enzyme inhibitor or receptor blocker were randomized to
      aldosterone blockade or placebo. The primary outcome at 16 weeks was percent
      change in coronary diameter to acetylcholine, and secondary outcome, coronary
      flow reserve to adenosine, both adjusted for baseline reactivity. RESULTS: Forty
      one women completed the treatment period with repeat coronary reactivity testing.
      Their mean age was 54 +/- 10 years; body mass index, 30 +/- 7.4 kg/m2; 12% had
      diabetes; and 15% had metabolic syndrome. There were no significant differences
      between treatment groups. At baseline, the percent change in reference vessel
      coronary diameter to acetylcholine was -5.0% in the aldosterone blockade group
      and -3.4% in the placebo group and, at 16 weeks, -7.2% in the aldosterone
      blockade group versus -14.3% in the placebo group (P = .15). At 16 weeks, the
      change in coronary flow reserve to intracoronary adenosine was -0.13 in the
      aldosterone blockade group versus -0.25 in the placebo group (P = .66).
      CONCLUSION: Adding aldosterone receptor blockade to angiotensin II inhibition did
      not improve coronary endothelial or microvascular function among women with signs
      and symptoms of ischemia in the setting of nonobstructive CAD.

PMID- 24890533
TI  - Implications of prior myocardial infarction for patients presenting with an acute
      myocardial infarction.
AB  - BACKGROUND: Prior myocardial infarction (MI) is a known risk factor for long-term
      mortality among acute MI patients; but its prevalence and implications for the
      short-term outcomes of patients with a new, acute MI remain uncertain. METHODS:
      We studied a total of 319,152 consecutively enrolled ST-segment elevation MI
      (STEMI) and non-STEMI (NSTEMI) patients in the National Cardiovascular Data
      Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get
      With The Guidelines (01/2007-03/2012). Baseline characteristics, home and in
      hospital treatments, mortality rates, and major bleeding were compared separately
      for STEMI and NSTEMI by prior MI status, with adjustment for mortality and major
      bleeding. RESULTS: Prior MI was documented in 19% of STEMI (n = 124,535) and 29%
      of NSTEMI (n = 194,617) patients, who were older, were more likely to have
      comorbidities or prior revascularization, and were more commonly taking secondary
      prevention medications at home. Guideline-recommended treatments in-hospital and
      at discharge did not differ in prior-MI STEMI patients, but invasive management
      was lower for prior-MI NSTEMI patients. The frequency of in-hospital mortality
      was higher for prior-MI STEMI (5.9% vs. 5.2%) and NSTEMI patients (4.3% vs.
      3.4%). After adjustment, the excess mortality risk associated with prior MI was
      no longer present for STEMI (odds ratio = 1.06, 95% CI 0.97-1.15), with only
      modest excess risk for NSTEMI (odds ratio = 1.10, 95% CI 1.04-1.15). The risk of
      in-hospital major bleeding was marginally lower for prior-MI NSTEMI. CONCLUSION:
      More than 20% of patients with acute MI treated in contemporary practice have a
      history of a prior MI; despite differences in the baseline risk profile, there
      was little difference in the adjusted risk of in-hospital mortality by prior-MI
      status.

PMID- 24890534
TI  - Prevalence and predictors of nonobstructive coronary artery disease identified
      with coronary angiography in contemporary clinical practice.
AB  - BACKGROUND: Guidelines recommend noninvasive tests (NITs) to risk stratify and
      identify patients with higher likelihood of coronary artery disease (CAD) prior
      to elective coronary angiography. However, a high percentage of patients are
      found to have nonobstructive CAD. We aimed to understand the relationship between
      patient characteristics, NIT findings, and the likelihood of nonobstructive CAD.
      METHODS: Patients undergoing elective catheterization without history of CAD were
      identified from 1,128 hospitals in National Cardiovascular Data Registry's
      CathPCI Registry between July 2009 and December 2011. Noninvasive tests included
      stress electrocardiogram, stress echocardiogram, stress radionuclide, stress
      cardiac magnetic resonance, and computed tomographic angiography. Patient
      demographics, risk factors, symptoms, and NIT results were correlated with the
      presence of nonobstructive CAD, defined as all native coronary stenoses <50%.
      RESULTS: Of 661,063 patients undergoing elective angiography, 386,003 (58.4%) had
      nonobstructive CAD. Preprocedure NIT was performed in 64% of patients; 51.9% were
      reported to be abnormal, but only 9% had high-risk findings. Independent factors
      associated with nonobstructive CAD were younger age, female sex, atypical chest
      pain, and a low-risk NIT. Patients with high-risk findings on NIT were more
      likely to have obstructive CAD (adjusted odds ratio 3.03 [2.86-3.22]).
      Noninvasive test findings had minimal incremental value beyond clinical factors
      for predicting obstructive disease (C index = 0.75 for clinical factors vs 0.74
      for NIT findings). CONCLUSION: In current practice, about two-thirds of patients
      undergo NIT prior to elective cardiac catheterization, yet most patients have
      nonobstructive CAD. The weak correlation between most NIT results and the
      likelihood of obstructive CAD provides further impetus for improving
      preangiography assessment of likelihood of disease.

PMID- 24890535
TI  - Elevated plasma galectin-3 is associated with near-term rehospitalization in
      heart failure: a pooled analysis of 3 clinical trials.
AB  - BACKGROUND: Rehospitalization is a major cause for heart failure (HF)-related
      morbidity and is associated with considerable loss of quality of life and costs.
      The rate of unplanned rehospitalization in patients with HF is unacceptably high;
      current risk stratification to identify patients at risk for rehospitalization is
      inadequate. We evaluated whether measurement of galectin-3 would be helpful in
      identifying patients at such risk. METHODS: We analyzed pooled data from patients
      (n = 902) enrolled in 3 cohorts (COACH, n = 592; PRIDE, n = 181; and UMD H-23258,
      n = 129) originally admitted because of HF. Mean patient age was between 61.6 and
      72.9 years across the cohorts, with a wide range of left ventricular ejection
      fraction. Galectin-3 levels were measured during index admission. We used fixed
      and random-effects models, as well as continuous and categorical reclassification
      statistics to assess the association of baseline galectin-3 levels with risk of
      postdischarge rehospitalization at different time points and the composite end
      point all-cause mortality and rehospitalization. RESULTS: Compared with patients
      with galectin-3 concentrations less than 17.8 ng/mL, those with results exceeding
      this value were significantly more likely to be rehospitalized for HF at 30, 60,
      90, and 120 days after discharge, with odds ratios (ORs) of 2.80 (95% CI 1.41
      5.57), 2.61 (95% CI 1.46-4.65), 3.01 (95% CI 1.79-5.05), and 2.79 (95% CI 1.75
      4.45), respectively. After adjustment for age, gender, New York Heart Association
      class, renal function (estimated glomerular filtration rate), left ventricular
      ejection fraction, and B-type natriuretic peptide, galectin-3 remained an
      independent predictor of HF rehospitalization. The addition of galectin-3 to risk
      models significantly reclassified patient risk of postdischarge rehospitalization
      and fatal event at each time point (continuous net reclassification improvement
      at 30 days of +42.6% [95% CI +19.9%-65.4%], P < .001). CONCLUSIONS: Among
      patients hospitalized for HF, plasma galectin-3 concentration is useful for the
      prediction of near-term rehospitalization.

PMID- 24890536
TI  - Association between alcohol consumption and systolic ventricular function: a
      population-based study.
AB  - BACKGROUND: Although moderate alcohol consumption is associated with decreased
      clinical heart failure, there are no population-based studies evaluating the
      relationship between alcohol consumption and left ventricular (LV) systolic
      function. We sought to evaluate the relationship between alcohol consumption and
      LV systolic function in the community. METHODS: In a population-based random
      sample of 2,042 adults, age >=45 years, we assessed alcohol consumption by a self
      administered questionnaire. Responders were categorized by alcohol consumption
      level: abstainer, former drinker, light drinker (<1 drink a day), moderate
      drinker (1-2 drinks a day), and heavy drinker (>2 drinks a day). Systolic
      function was assessed by echocardiography. RESULTS: We identified 38 cases of
      systolic dysfunction in 182 abstainers, 309 former drinkers, 1,028 light
      drinkers, 251 moderate drinkers, and 146 heavy drinkers. A U-shaped relationship
      was observed between alcohol consumption and moderate systolic dysfunction (LV
      ejection fraction [LVEF] <=40%), with the lowest prevalence in light drinkers
      (0.9%) compared to the highest prevalence in heavy drinkers (5.5%) (odds ratio
      0.14, 95% CI 0.04-0.43). This association persisted across different strata of
      risk factors of systolic dysfunction as well as in multivariate analysis. No
      significant association between alcohol consumption and systolic function was
      seen in subjects with LVEF >50% or <=50%. CONCLUSIONS: There is a U-shaped
      relationship between alcohol consumption volume and LVEF, with the lowest risk of
      moderate LV dysfunction (LVEF <=40%) observed in light drinkers (<1 drink a day).
      These findings are parallel to the relationship between alcohol consumption and
      cardiovascular disease prevalence.

PMID- 24890538
TI  - The pulmonary capillary wedge pressure accurately reflects both normal and
      elevated left atrial pressure.
AB  - BACKGROUND: Pulmonary capillary wedge pressure (PCWP) is routinely used as an
      indirect measure of the left atrial pressure (LAP), although the accuracy of this
      estimate, especially under pathological hemodynamic conditions, remains
      controversial. OBJECTIVES: The aim of this prospective study was to investigate
      the reliability of PCWP for the evaluation of LAP under different hemodynamic
      conditions. METHODS: Simultaneous left and right heart catheterization data of
      117 patients with pure mitral stenosis, obtained before and immediately after
      percutaneous mitral comissurotomy, were analyzed. RESULTS: A strong correlation
      and agreement between PCWP and LAP measurements was demonstrated (correlation
      coefficient = 0.97, mean bias +/- CI, 0.3 +/- -3.7 to 4.2 mm Hg). Comparison of
      measurements performed within a 5-minute interval and those performed
      simultaneously revealed that simultaneous pressure acquisition yielded better
      agreement between the 2 methods (bias +/- CI, 1.82 +/- 1.98 mm Hg). In contrast
      to previous observations, the discrepancy between the 2 measures did not increase
      with elevated PCWP. Multiple regression analysis failed to identify hemodynamic
      confounders of the discrepancy between the 2 pressures. The ability of PCWP to
      distinguish between normal and elevated LAP (cutoff set at 12 and 15 mm Hg,
      respectively), as tested by receiver operating characteristics analysis,
      demonstrated a remarkably high diagnostic accuracy (area under the curve: 0.989
      and 0.996, respectively). CONCLUSIONS: Although the described limits of agreement
      may not allow the interchangeability of PCWP and LAP, especially at lower
      pressure ranges, our data support the clinical use of PCWP as a robust and
      accurate estimate of LAP.

PMID- 24890539
TI  - Spatial heterogeneity of neoatherosclerosis and its relationship with
      neovascularization and adjacent plaque characteristics: optical coherence
      tomography study.
AB  - BACKGROUND: Development of neoatherosclerosis (NA) has been reported to be a
      potential cause of late stent failure. However, the distribution of NA and its
      relationship with neovascularization (NV) and adjacent plaque characteristics
      remain unclear. METHODS: We investigated 167 stents (40 bare-metal stents, 84
      sirolimus-eluting stents, and 43 everolimus-eluting stents) with optical
      coherence tomography. Each stent was divided into the proximal section (PS), mid
      section (MS) and distal section (DS). Neoatherosclerosis was defined as lipid
      laden neointima or calcification inside stent. Adjacent plaque characteristics
      were evaluated within 5 mm proximal and distal reference segments. RESULTS:
      Neoatherosclerosis was more frequent in PS and DS than in MS (PS 19.8% vs. MS
      3.6% vs. DS 21%: PS vs. MS, P < .001: MS vs. DS, P < .001). Neovascularization in
      PS and DS was also more prevalent compared with that in MS (PS 15% vs. MS 5.4%
      vs. DS 13.8%: PS vs. MS, P = .001: MS vs. DS, P = .001). Neoatherosclerosis was
      more frequently observed in stents with intraintima NV (68.6% vs. 20.5%, P <
      .001). The incidence of NA was higher, when adjacent plaque was lipid (43.2% with
      lipid plaque vs. 12.2% without lipid plaque, P < .001). CONCLUSION:
      Neoatherosclerosis occurs more frequently at PS and DS. Neoatherosclerosis was
      associated with NV and adjacent lipid plaque, suggesting potential
      interrelationship between development of NA and NV and adjacent plaque
      characteristics.

PMID- 24890540
TI  - Ten-year clinical follow-up after sirolimus-eluting stent implantation.
AB  - BACKGROUND: Little is known on the "very" long-term incidence of major adverse
      cardiac events (MACE), target-lesion revascularization (TLR), target-vessel
      revascularization and stent thrombosis after sirolimus-eluting stent (SES)
      implantation. We present the first study to provide a 10-year clinical follow-up
      in an unselected patient population who underwent SES implantation. METHODS AND
      RESULTS: We ran a systematic 10-year clinical follow-up in a series of 200
      consecutive patients treated with unrestricted SES implantation between April
      2002 and April 2003 in two Swiss hospitals. Outcomes and follow-up were obtained
      in all 200 patients. The cumulative 10-year MACE rate was 47% with all-cause
      death of 20%, cardiac death of 9%, myocardial infarction of 7%, TLR and target
      vessel revascularization of 8% and 11% respectively. Academic Research Consortium
      defined "definite and probable" stent thrombosis-rate was 2.5%. TLR risk was
      maximal between 3 to 6 years. New lesion revascularization increased throughout
      the study period. CONCLUSION: Incidence of TLR was maximal 3 to 6 years after SES
      implantation and decreased thereafter. MACE and non-TLR revascularization rates
      steadily increased during the complete follow-up underlining the progression of
      coronary artery disease.

PMID- 24890537
TI  - Association of electrocardiogram abnormalities and incident heart failure events.
AB  - Unless effective preventive strategies are implemented, aging of the population
      will result in a significant worsening of the heart failure (HF) epidemic. Few
      data exist on whether baseline electrocardiographic (ECG) abnormalities can
      refine risk prediction for HF. METHODS: We examined a prospective cohort of 2,915
      participants aged 70 to 79 years without preexisting HF, enrolled between April
      1997 and June 1998 in the Health, Aging, and Body Composition (Health ABC) study.
      Minnesota Code was used to define major and minor ECG abnormalities at baseline
      and at year 4 follow-up. Using Cox models, we assessed (1) the association
      between ECG abnormalities and incident HF and (2) the incremental value of adding
      ECG to the Health ABC HF Risk Score using the net reclassification index.
      RESULTS: At baseline, 380 participants (13.0%) had minor, and 620 (21.3%) had
      major ECG abnormalities. During a median follow-up of 11.4 years, 485
      participants (16.6%) developed incident HF. After adjusting for the Health ABC HF
      Risk Score variables, the hazard ratio (HR) was 1.27 (95% CI 0.96-1.68) for minor
      and 1.99 (95% CI 1.61-2.44) for major ECG abnormalities. At year 4, 263
      participants developed new and 549 had persistent abnormalities; both were
      associated with increased subsequent HF risk (HR 1.94, 95% CI 1.38-2.72 for new
      and HR 2.35, 95% CI 1.82-3.02 for persistent ECG abnormalities). Baseline ECG
      correctly reclassified 10.5% of patients with HF events, 0.8% of those without HF
      events, and 1.4% of the overall population. The net reclassification index across
      the Health ABC HF risk categories was 0.11 (95% CI 0.03-0.19). CONCLUSIONS: Among
      older adults, baseline and new ECG abnormalities are independently associated
      with increased risk of HF. The contribution of ECG screening for targeted
      prevention of HF should be evaluated in clinical trials.

PMID- 24890541
TI  - Arterial access site utilization in cardiogenic shock in the United Kingdom: is
      radial access feasible?
AB  - BACKGROUND: Cardiogenic shock (CS) remains the leading cause of mortality in
      patients hospitalized with acute myocardial infarction (AMI). The transradial
      access site (TRA) has become increasingly adopted as a default access site for
      percutaneous coronary intervention (PCI); however, even in experienced centers
      that favor the radial artery as the primary access site during PCI, patients
      presenting in CS are often treated via the transfemoral access site (TFA); and
      commentators have suggested that CS remains the final frontier that has given
      even experienced radial operators pause. We studied the use of TRA in patients
      presenting in CS in a nonselected high-risk cohort from the British
      Cardiovascular Intervention database over a 7-year period (2006-2012). METHODS:
      Mortality (30-day) and major adverse cardiac and cerebrovascular events (a
      composite of in-hospital mortality, in-hospital myocardial reinfarction, target
      vessel revascularization, and cerebrovascular events) were studied based on TFA
      and TRA utilization in CS patients. The influence of access site selection was
      studied in 7,231 CS patients; TFA was used in 5,354 and TRA in 1,877 patients.
      RESULTS: Transradial access site was independently associated with a lower 30-day
      mortality (hazard ratio [HR] 0.56, 95% CI 0.46-0.69, P = 0 < .001), in-hospital
      major adverse cardiac and cerebrovascular events (HR 0.64, 95% CI 0.53-0.76, P <
      .0001) and major bleeding (HR 0.37, 95% CI 0.18-0.73, P = .004). CONCLUSIONS:
      Although the majority of PCI cases performed in patients with cardiogenic shock
      in the United Kingdom are performed through the TFA, the radial artery represents
      an alternative viable access site in this high-risk cohort of patients in
      experienced centers.

PMID- 24890542
TI  - Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg)
      prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid
      Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study.
AB  - In ST-elevation myocardial infarction (STEMI) patients, residual platelet
      reactivity soon after a loading dose (LD) of prasugrel or ticagrelor is higher
      than that reported for healthy volunteers or subjects with stable coronary artery
      disease; and the majority of primary percutaneous coronary intervention (PPCI)
      procedures with bivalirudin monotherapy are performed without proper platelet
      inhibition. However, ticagrelor LD is just the daily dose, whereas prasugrel LD
      is 6-fold the long-term daily dose. We hypothesized that an increased ticagrelor
      LD may result in a faster and more effective platelet inhibition as compared with
      the standard prasugrel LD. METHODS: Fifty patients with STEMI, pretreated with
      intravenous aspirin, undergoing PPCI were randomized to receive prasugrel 60-mg
      LD (n = 25) or ticagrelor 360-mg LD (n = 25). Residual platelet reactivity was
      assessed by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD.
      RESULTS: At the time of LD, 90% of enrolled patients had an aspirin reactivity
      unit value <550. P2Y12 reaction units 1 hour after the LD (study primary end
      point) were 236 (129-289) and 248 (115-304) in the prasugrel and ticagrelor
      group, respectively (P = .899). High residual platelet reactivity (P2Y12 reaction
      units >=240) was found in 43% and 56% of patients (P = .386) at 1 hour and in 30%
      and 32% of patients (P = .907) at 2 hours, respectively. There was no significant
      difference in bleeding, arrhythmias, or dyspnea episodes in the 2 groups.
      CONCLUSIONS: In patients with STEMI undergoing PPCI, double (360 mg) ticagrelor
      LD failed to achieve a faster and more intense platelet inhibition as compared
      with the standard prasugrel LD. Intravenously administered aspirin allowed to
      achieve a very early inhibition of acid arachidonic pathway.

PMID- 24890543
TI  - Association between prehospital electrocardiogram use and patient home distance
      from the percutaneous coronary intervention center on total reperfusion time in
      ST-segment-elevation myocardial infarction patients: a retrospective analysis
      from the national cardiovascular data registry.
AB  - BACKGROUND: Current guidelines recommend <=90 minutes from first medical contact
      to percutaneous coronary intervention (FMC2B) for ST-segment-elevation myocardial
      infarction (STEMI) patients. We evaluated the relationship between patient home
      distance from a percutaneous coronary intervention (PCI) center, prehospital
      electrocardiogram (ECG) use, and FMC2B time among patients with STEMI. METHODS:
      We performed a retrospective cohort study including all STEMI patients in the
      ACTION-Get With The Guidelines registry from July 1, 2008, to September 30, 2012,
      who were transported by ambulance to a PCI center. Patient home distance was
      defined as the driving distance from the patient's home zip code to the PCI
      center address. Distance was classified into tertiles, and linear regression was
      used to characterize the interaction between prehospital ECG use and patient home
      distance with respect to FMC2B time. RESULTS: Of the 29,506 STEMI patients,
      19,690 (67%) received a prehospital ECG. The median patient home distance to the
      PCI center was 11.0 miles among patients with and 9.9 miles among those without a
      prehospital ECG. Prehospital ECGs were associated with a 10-minute reduction in
      the FMC2B time (P < .0001), which was consistent across distance tertiles (11 vs
      11 vs 10 minutes). The association between prehospital ECGs and shorter FMC2B was
      attenuated by 0.8 minute for every 10-mile increase in distance (interaction P =
      .0002). CONCLUSIONS: Prehospital ECGs are associated with a 10-minute reduction
      in the FMC2B time. However, patient home distance from a PCI center does not
      substantially change this association.

PMID- 24890545
TI  - Letter to the editor regarding the results of the MULIN CRT study published in
      the American Heart Journal.

PMID- 24890544
TI  - Characteristics of pediatric cardiovascular clinical trials registered on
      ClinicalTrials.gov.
AB  - BACKGROUND: ClinicalTrials.gov is an National Institutes of Health-sponsored
      registry of federally and privately funded trials. We sought to determine
      fundamental characteristics of registered pediatric cardiovascular trials
      (PCVTs). METHODS: A data set including 68,134 interventional clinical trials was
      downloaded from ClinicalTrials.gov and entered into a relational database.
      Aggregate data from PCVTs were compared with other trial specialties.
      Multivariable logistic regression was used to evaluate factors associated with
      improved trial quality metrics including blinding and randomization. RESULTS:
      Between July 1, 2005, and September 27, 2010, 5035 (7%) registered trials
      targeted pediatric populations, including 213 PCVTs (4.2%), 1,176 pediatric
      infectious disease trials (23%), 664 pediatric mental health trials (13%), and
      346 pediatric hematology/oncology trials (7%). Median (interquartile range) PCVT
      enrollment was 65 subjects (36-186) and median study duration was 2.3 years (1.3
      3.7). The most common PCVTs targeted acquired diseases including hypertension (n
      = 41, 14%), obesity (n = 26, 9%), pulmonary hypertension (n = 25, 9%), and
      dyslipidemia (n = 19, 7%). Important factors associated with improved quality
      metrics included National Institutes of Health as opposed to industry funding
      (OR, 1.9; P < .0001); trial location (trials with both US and foreign enrollment
      vs trials with US only or foreign only enrollment, P = .02) and trials restricted
      to younger children as opposed to trials including adolescents (OR, 1.4; P <
      .0001). CONCLUSION: PCVTs represent a small proportion of clinical trials
      relative to other pediatric subspecialties. Most PCVTs tend to parallel adult
      morbidities while there is a relative paucity of trials focused on congenital
      heart disease. These data may be useful to stakeholders in informing decisions
      regarding the conduct of PCVTs, and to provide insight into mechanisms to advance
      PCVT infrastructure.

PMID- 24890546
TI  - Reply to letter to the editor by Goel and Kapoor.

PMID- 24890547
TI  - The "smoker paradox" in older patients with non-ST-segment elevation myocardial
      infarction in the CRUSADE Registry.

PMID- 24890548
TI  - Response to letter to the editor by Lin et al.

PMID- 24890549
TI  - Protracted hypocalcaemia following a single dose of denosumab in humoral
      hypercalcaemia of malignancy due to PTHrP-secreting neuroendocrine tumour.

PMID- 24890550
TI  - Unexplained syncope: implications of age and gender on patient characteristics
      and evaluation, the diagnostic yield of an implantable loop recorder, and the
      subsequent treatment.
AB  - BACKGROUND: Syncope is a common clinical problem with a variety of underlying
      mechanisms, some of which occur more frequently in 1 of the sexes or at a certain
      age. HYPOTHESIS: There may be clinically significant age- and gender-related
      differences in patients with unexplained syncope. METHODS: Five hundred seventy
      patients (54% women) with unexplained syncope received an implantable loop
      recorder (ILR) and were followed until diagnosis or for at least 1 year. RESULTS:
      Women were older and more prone to severe trauma during syncope (40.8% vs 29.9%,
      P = 0.007), and hospitalization was more common at >=65 years (P = 0.003) without
      gender difference. Muscle spasms or grand mal seizures were more common in men
      and at <65 years old. Carotid sinus pressure, exercise testing, coronary
      angiography and magnetic resonance imaging/computed tomography scans were more
      commonly performed in men, whereas no test was more common in women. Tilt
      testing, exercise test, electroencephalography, and neurological or psychiatric
      evaluation were more common at >=65 years. There were no age- or gender-related
      differences in the diagnostic yield of the ILR, whereas patients >=65 years old
      more often received specific treatment based on ILR data. CONCLUSIONS: Gender
      and/or age had relevance for the clinical evaluation, rate of recurrence, and
      subsequent specific treatment but not for the diagnostic yield of the ILR.

PMID- 24890551
TI  - Internet-based survey of factors associated with subjective feeling of insomnia,
      depression, and low health-related quality of life among Japanese adults with
      sleep difficulty.
AB  - BACKGROUND: This study was conducted to determine what symptom components or
      conditions of insomnia are related to subjective feelings of insomnia, low health
      related quality of life (HRQOL), or depression. METHOD: Data from 7,027 Japanese
      adults obtained using an Internet-based questionnaire survey was analyzed to
      examine associations between demographic variables and each sleep difficulty
      symptom item on the Pittsburgh Sleep Quality Index (PSQI) with the
      presence/absence of subjective insomnia and scores on the Short Form-8 (SF-8) and
      Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: Prevalence of
      subjective insomnia was 12.2% (n = 860). Discriminant function analysis revealed
      that item scores for sleep quality, sleep latency, and sleep medication use on
      the PSQI and CES-D showed relatively high discriminant function coefficients for
      identifying positivity for the subjective feeling of insomnia. Among respondents
      with subjective insomnia, a low SF-8 physical component summary score was
      associated with higher age, depressive state, and PSQI items for sleep difficulty
      and daytime dysfunction, whereas a low SF-8 mental component summary score was
      associated with depressive state, PSQI sleep latency, sleeping medication use,
      and daytime dysfunction. Depressive state was significantly associated with sleep
      latency, sleeping medication use, and daytime dysfunction. CONCLUSION: Among
      insomnia symptom components, disturbed sleep quality and sleep onset insomnia may
      be specifically associated with subjective feelings of the disorder. The
      existence of a depressive state could be significantly associated with not only
      subjective insomnia but also mental and physical QOL. Our results also suggest
      that different components of sleep difficulty, as measured by the PSQI, might be
      associated with mental and physical QOL and depressive status.

PMID- 24890553
TI  - Response to letter to editor from Dr Walshe.

PMID- 24890554
TI  - String test of hypervirulent Klebsiella pneumonia.

PMID- 24890552
TI  - Mitochondria-targeted spin traps: synthesis, superoxide spin trapping, and
      mitochondrial uptake.
AB  - Development of reliable methods and site-specific detection of free radicals is
      an active area of research. Here, we describe the synthesis and radical-trapping
      properties of new derivatives of DEPMPO and DIPPMPO, bearing a mitochondria
      targeting triphenylphosphonium cationic moiety or guanidinium cationic group. All
      of the spin traps prepared have been observed to efficiently trap superoxide
      radical anions in a cell-free system. The superoxide spin adducts exhibited
      similar spectral properties, indicating no significant differences in the
      geometry of the cyclic nitroxide moieties of the spin adducts. The superoxide
      adduct stability was measured and observed to be highest (t1/2 = 73 min) for
      DIPPMPO nitrone linked to triphenylphosphonium moiety via a short carbon chain
      (Mito-DIPPMPO). The experimental results and DFT quantum chemical calculations
      indicate that the cationic property of the triphenylphosphonium group may be
      responsible for increased superoxide trapping efficiency and adduct stability of
      Mito-DIPPMPO, as compared to the DIPPMPO spin trap. The studies of uptake of the
      synthesized traps into isolated mitochondria indicated the importance of both
      cationic and lipophilic properties, with the DEPMPO nitrone linked to the
      triphenylphosphonium moiety via a long carbon chain (Mito10-DEPMPO) exhibiting
      the highest mitochondrial uptake. We conclude that, of the synthesized traps,
      Mito-DIPPMPO and Mito10-DEPMPO are the best candidates for potential mitochondria
      specific spin traps for use in biologically relevant systems. 

PMID- 24890555
TI  - Bland-White-Garland syndrome.

PMID- 24890556
TI  - Helicobacter pylori infection increases subsequent ischemic stroke risk: a
      nationwide population-based retrospective cohort study.
AB  - BACKGROUND AND PURPOSE: The association of Helicobacter pylori infection (HP-I)
      with ischemic stroke (IS) incidence has been studied, but conflicting results
      have been reported. The purpose of this study was to investigate the association
      between chronic HP-I and the risk of acute IS by using data from the Taiwan
      National Health Insurance Research Database. METHODS: We identified17 332
      patients with HP-I and 69 328 randomly selected age- and gender-matched controls
      from 1 January 2000 to 31 December 2010. Both cohorts were followed up until the
      occurrence of IS or until censored. The Cox proportional hazards model was used
      for assessing the association of HP-I with IS. RESULTS: Compared with the control
      cohort, patients diagnosed with HP-I exhibited a higher incidence rate of IS
      (14.8 vs. 8.45 per 1000 person years) and a hazard ratio (HR) of 1.52 (95%
      confidence interval [CI] = 1.40-1.65). The HRs for IS were 1.49 (1.37-1.62) in
      patients diagnosed with HP-I who had one admission, increasing to 2.26 (1.71
      1.98) for those who had two or more admissions when adjusted for age, sex and
      comorbidities (P for trend < 0.0001). In addition, we observed a significantly
      positive association between nonembolic IS and increased admissions (P for trend
      < 0.0001) but negative association with embolic IS. CONCLUSION: Chronic HP-I is
      significantly associated with an increased risk of IS, particularly nonembolic
      IS. Anti-HP therapy may be beneficial to IS prevention.

PMID- 24890557
TI  - Massive subcutaneous emphysema in a long-term ventilated patient.

PMID- 24890558
TI  - Apical hypertrophic cardiomyopathy: the spade of hearts.

PMID- 24890559
TI  - A canine bug in a human heart.

PMID- 24890560
TI  - Is 30 minutes between doses long enough in oral food challenges?

PMID- 24890562
TI  - Effects of nanostructure geometry on nanoimprinted polymer photovoltaics.
AB  - We demonstrate the effects of nanostructure geometry on the nanoimprint induced
      poly(3-hexylthiophene-2,5-diyl) (P3HT) chain alignment and the performance of
      nanoimprinted photovoltaic devices. Out-of-plane and in-plane grazing incident X
      ray diffraction techniques are employed to characterize the nanoimprint induced
      chain alignment in P3HT nanogratings with different widths, spacings and heights.
      We observe the dependence of the crystallite orientation on nanostructure
      geometry such that a larger width of P3HT nanogratings leads to more edge-on
      chain alignment while the increase in height gives more vertical alignment.
      Consequently, P3HT/[6,6]-phenyl-C61-butyric-acid-methyl-ester (PCBM) solar cells
      with the highest density and aspect ratio P3HT nanostructures show the highest
      power conversion efficiency among others, which is attributed to the efficient
      charge separation, transport and light absorption. 

PMID- 24890561
TI  - Pharmacovigilance in practice: erythropoiesis-stimulating agents.
AB  - Pharmacovigilance (PV) is the science and activities relating to the detection,
      assessment, understanding, and prevention of adverse effects or other problems
      related to medical products after they have been licensed for marketing. The
      purpose of PV is to advance the safe use of marketed medical products. Regulatory
      agencies and license holders collaborate to collect data reported by health care
      providers, patients, and the public as well as data from systematic reviews, meta
      analyses, and individual clinical and nonclinical studies. They validate and
      analyze the data to determine whether safety signals exist, and if warranted,
      develop an action plan to mitigate the identified risk. Erythropoiesis
      stimulating agents (ESAs) provide an example of how PV is applied in reality.
      Among other approved indications, ESAs may be used to treat anemia in patients
      with chemotherapy-induced anemia. ESAs increase hemoglobin levels and reduce the
      need for transfusions; they are also associated with a known increased risk of
      thromboembolic events. Starting in 2003, emerging data suggested that ESAs might
      reduce survival. As a result of PV activities by regulatory agencies and license
      holders, labeling for ESAs addresses these risks. Meta-analyses and individual
      clinical studies have confirmed that ESAs increase the risk of thromboembolic
      events, but when used as indicated, ESAs have not been shown to have a
      significant effect on survival or disease progression. Ongoing safety studies
      will provide additional data in the coming years to further clarify the risks and
      benefits of ESAs. 

PMID- 24890563
TI  - Intestinal alpha-glucosidase and some pancreatic enzymes inhibitory effect of
      hydroalcholic extract of Moringa stenopetala leaves.
AB  - BACKGROUND: Moringa stenopetala has been used in traditional health systems to
      treat diabetes mellitus. One of the successful methods to prevent of the onset of
      diabetes is to control postprandial hyperglycemia by the inhibition of alpha
      glucosidase and pancreatic alpha-amylase activities, resulting in the aggressive
      delay of the carbohydrate digestion of absorbable monosaccharides. The aim of the
      present study is to investigate the effect of the extract of the leaves of
      Moringa stenopetala on alpha-glucosidase, pancreatic alpha-amylase, pancreatic
      lipase, and pancreatic cholesterol esterase activities, and, therefore find out
      the relevance of the plant in controlling blood sugar and lipid levels. METHODS:
      The dried leaves of Moringa stenopetala were extracted with hydroalcoholic
      solvent and dried using rotary vapor under reduced pressure. The dried extracts
      were determined for the total phenolic compounds, flavonoid content and condensed
      tannins content by using Folin-Ciocateu's reagent, AlCl3 and vanillin assay,
      respectively. The dried extract of plant-based food was further quantified with
      respect to intestinal alpha-glucosidase (maltase and sucrase) inhibition and
      pancreatic alpha-amylase inhibition by glucose oxidase method and
      dinitrosalicylic (DNS) reagent, respectively. RESULTS: The phytochemical analysis
      indicated that flavonoid, total phenolic, and condensed tannin contents in the
      extract were 71.73 +/- 2.48 mg quercetin equivalent/g of crude extract, 79.81 +/-
      2.85 mg of gallic acid equivalent/g of crude extract, 8.82 +/- 0.77 mg catechin
      equivalent/g of crude extract, respectively. The extract inhibited intestinal
      sucrase more than intestinal maltase with IC50 value of 1.47 +/- 0.19 mg/ml. It
      also slightly inhibited pancreatic alpha-amylase, pancreatic lipase and
      pancreatic cholesterol esterase. CONCLUSION: The result demonstrated the
      beneficial biochemical effects of Moringa stenopetala by inhibiting intestinal
      alpha-glucosidase, pancreatic cholesterol esterase and pancreatic lipase
      activities. A daily supplement intake of the leaves of Moringa stenopetala may
      help in reducing hyperglycemia and hyperlipidemia.

PMID- 24890564
TI  - Structure-based design, synthesis, and biological evaluation of isatin
      derivatives as potential glycosyltransferase inhibitors.
AB  - Peptidoglycan glycosyltransferase (PGT) has been shown to be an important
      pharmacological target for the inhibition of bacterial cell wall biosynthesis.
      Structure-based virtual screening of about 3,000,000 commercially available
      compounds against the crystal structure of the glycosyltransferase (GT) domain of
      the Staphylococcus aureus penicillin-binding protein 2 (S. aureus PBP2) resulted
      in identification of an isatin derivative, 2-(3-(2-carbamimidoylhydrazono)-2
      oxoindolin-1-yl)-N-(m-tolyl)acetamide (4) as a novel potential GT inhibitor. A
      series of 4 derivatives were synthesized. Several compounds showed more active
      antimicrobial activity than the initial hit compound 4, in particular 2-(3-(2
      carbamimidoylhydrazono)-2-oxoindolin-1-yl)-N-(3-nitrophenyl)acetamide (4l),
      against Gram-positive Bacillus subtilis and S. aureus with MIC values of 24 and
      48 MUg/mL, respectively. Saturation transfer difference (STD) NMR study revealed
      that there is a binding contact between 4l and the GT domain of S. aureus PBP2.
      Competitive STD-NMR further proved that 4l and moenomycin A bind to GT domain in
      a competitive manner. Molecular docking study suggests a potential binding pocket
      of 4l in the GT domain of S. aureus PBP2. Taken together, compound 4l would
      provide a new scaffold for further development of potent GT inhibitors.

PMID- 24890565
TI  - Chemical restraint of African mole-rats (Fukomys sp.) with a combination of
      ketamine and xylazine.
AB  - OBJECTIVE: To establish an accurate anaesthetic dose for chemical restraint of
      African mole-rats using ketamine and xylazine. STUDY DESIGN: Prospective
      nonrandomized laboratory study. ANIMALS: Sixteen adult Ansell's mole-rats
      (Fukomys anselli) and eight giant mole-rats (F. mechowii). METHODS: Fukomys
      anselli of different ages, sexes and reproductive status were systematically
      anaesthetized starting with an intramuscular injection of ketamine (2.5 mg kg(-1)
      ) and increasing the doses in steps of 0.5 mg kg(-1) until loss of the righting
      reflex (LRR) was observed. Xylazine was added to a constant dose of ketamine,
      starting at 0.5 mg kg(-1) that was increased by 0.5 mg kg(-1) in further trials.
      Once an effective combination was established and evaluated in F. anselli, it was
      also tested in F. mechowii. Heart and respiratory rates and rectal temperatures
      were measured during anaesthesia. anova for repeated measures and Student's t
      test were used to compare means. RESULTS: Chemical restraint was accomplished at
      a dose of 6 mg kg(-1) ketamine combined with 2.5 mg kg(-1) xylazine. LRR lasted
      on average mean 56 +/- SD 19 minutes (F. anselli) and 140 +/- 41 minutes (F.
      mechowii). Loss of pedal withdrawal reflex (LPR) lasted for 20 +/- 15 minutes (F.
      anselli) and for 29 +/- 2 minutes (F. mechowii), respectively. All animals
      recovered satisfactorily. Heart and respiratory rates were stable during
      anaesthesia, but rectal temperature fell significantly in F. mechowii after
      losing the righting reflex (LRR) from T1 (32.6 +/- 0.6  degrees C) to T3 (30.4 +/
      0.9  degrees C). CONCLUSIONS AND CLINICAL RELEVANCE: African mole-rats
      (Bathyergidae) live in closed burrow systems under particular conditions
      (hypercapnia, hypoxia, stable temperature, humidity, darkness) and show several
      physiological adaptations. Injectable anaesthetics in the dose rates used in
      other rodents are not appropriate for use in these subterranean species. Here, a
      reliable protocol for chemical restraint is provided.

PMID- 24890567
TI  - An update on the incidence of dengue gaining strength in Saudi Arabia and current
      control approaches for its vector mosquito.
AB  - BACKGROUND: The cases of dengue reported earlier in the late 1990s from the
      Kingdom of Saudi Arabia (KSA) occurred in the cities of Jeddah and Makkah.
      Although the kingdom has ample financial resources to establish effective control
      measures for the dengue vector, numerous cases of dengue occur and fluctuate in
      numbers from year to year. This necessitates a serious review of the current
      vector control strategies being practiced in order to identify the existing
      shortcomings. This short report provides an update on epidemiology of dengue in
      KSA (specifically in cities of Jeddah and Makkah) with a critical look at the
      current vector control strategies. FINDINGS: In 2013, 4411 cases of dengue were
      reported, with 8 cases of mortality. This number of dengue incidence was four
      times higher compared to 2012. In 2013, the highest number of 1272 dengue cases
      was reported in May, while the lowest number (37) of cases was reported in
      September. CONCLUSIONS: It is evident that the control strategies of the dengue
      vector presently employed are inadequate. There seems to be serious deficiencies
      in following proper scientific procedures during field application(s) of control
      materials against the vector as is evident by the increases in the number of
      dengue cases as well as frequent outbreaks of the vector mosquito populations. In
      this review, some specific suggestions are made to draw attention to the relevant
      KSA authorities of the possible reasons behind unsuccessful control results and
      as to how to improve the strategy of dengue vector control in the kingdom.

PMID- 24890566
TI  - The role of CXCL10 in the pathogenesis of experimental septic shock.
AB  - INTRODUCTION: The chemokine CXCL10 is produced during infection and inflammation
      to activate the chemokine receptor CXCR3, an important regulator of lymphocyte
      trafficking and activation. The goal of this study was to assess the
      contributions of CXCL10 to the pathogenesis of experimental septic shock in mice.
      METHODS: Septic shock was induced by cecal ligation and puncture (CLP) in mice
      resuscitated with lactated Ringer's solution and, in some cases, the broad
      spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and
      mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included
      leukocyte trafficking and activation, core body temperature, plasma cytokine
      concentrations, bacterial clearance and survival. RESULTS: CXCL10 was present at
      high concentrations in plasma and peritoneal cavity during CLP-induced septic
      shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and
      mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice
      treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations
      of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and
      lessened natural killer (NK) cell activation compared to control mice. Compared
      to control mice, bacterial burden in blood and lungs was lower in CXCL10
      deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice
      with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP
      significantly improved survival compared to mice treated with non-specific IgG
      under the same conditions. CONCLUSIONS: CXCL10 plays a role in the pathogenesis
      of CLP-induced septic shock and could serve as a therapeutic target during the
      acute phase of septic shock.

PMID- 24890568
TI  - Role of CD151 expression in gallbladder carcinoma.
AB  - INTRODUCTION: CD151 is a member of the tetraspanin family, which interacts with
      laminin-binding integrins and other tetraspanins. CD151 is involved in several
      pathologic activities associated with tumor progression, including metastasis and
      angiogenesis. The aim of this study was to clarify the clinical use of CD151
      expression in gallbladder cancer (GBC). METHODS: Forty-five patients with GBC who
      had undergone operative treatment were enrolled in this study. Expressions of
      CD151 in the resected GBC specimens were evaluated with anti-CD151 antibody. The
      patients were divided into positive and negative groups according to CD151
      expression: CD151-positive group (n = 26) and CD151-negative group (n = 19).
      Clinicopathologic factors, including Ki-67 and matrix metallopeptidase 9, also
      were compared between the two groups. RESULTS: CD151-positive expression was 58%
      and correlated with poorer prognosis; 5-year survival of CD151-positive and CD151
      negative groups was 29% and 78%, respectively (P = .006). CD151 expression also
      correlated with lymphatic invasion and curability. Multivariate analysis revealed
      that CD151-positive expression was an independent prognostic factor (hazard ratio
      2.97, P = .02). In addition, CD151 expression correlated with matrix
      metallopeptidase 9 expression (P < .05) but not with Ki67 expression. CONCLUSION:
      Those findings suggested that CD151-positive expression might be a potential
      prognostic indicator and one of the target molecules for the regulation of tumor
      metastasis for patients with GBC.

PMID- 24890569
TI  - Psoriasis as a model of exaggerated, not dysregulated, wound healing presents
      potential therapeutic targets for enhanced tissue repair integrity and diminished
      scaling.

PMID- 24890570
TI  - Comparison of postoperative complication risk prediction approaches based on
      factors known preoperatively to surgeons versus patients.
AB  - BACKGROUND: Estimating the risk of postoperative complications can be performed
      by surgeons with detailed clinical information or by patients with limited
      information. Our objective was to compare three estimation models: (1) the All
      Information Model, using variables available from the American College of
      Surgeons National Surgical Quality Improvement Program (ACS NSQIP); (2) the
      Surgeon Assessment Model, using variables available to surgeons preoperatively,
      and (3) the Patient-Entered Model, using information that patients know about
      their own health. STUDY DESIGN: Using the ACS NSQIP 2011 data for general and
      colon surgery, standard ACS NSQIP regression methods were used to develop models.
      Each model examined Overall and Serious Morbidity as outcomes. The models were
      assessed using the c-statistic, Hosmer-Lemshow statistic, and Akaike Information
      Criterion. RESULTS: The overall morbidity rate was 13.0%, and the serious
      morbidity rate was 10.5% for patients undergoing general surgery (colon surgery:
      31.8% and 26.0%, respectively). There was a small decrement in the c-statistic as
      the number of predictors decreased. The Akaike Information Criterion likelihood
      ratio increased between the All Information and Surgeon Assessment models, but
      decreased in the Patient-Entered Model. The Hosmer-Lemshow statistic suggested
      good model fit for five colon surgery models and one general surgery model.
      CONCLUSION: Although a small decline in model performance was observed, the
      magnitude suggests that it may not be clinically meaningful as the risk
      predictions offered are superior to simply providing unadjusted complications
      rates. The Surgeon Assessment and Patient-Entered models with fewer predictors
      can be used with relative confidence to predict a patient's risk.

PMID- 24890571
TI  - The influence of medical cost controls implemented by Taiwan's national health
      insurance program on doctor-patient relationships.
AB  - To prevent medical costs from rising, the National Health Insurance
      administration implemented the global budget system for financial reform,
      effective 1 July 2004. Since the implementation of this system, patients have
      been required to pay for some medicines to limit costs to the system. More
      recently, as they have faced constant increases in health insurance fees and also
      faced an increase in the number of medical expenses they must pay during an
      economic recession and a rise in unemployment, would the economic burden on the
      people of Taiwan not be increased? Even though National Health Insurance is a
      form of social insurance, does it guarantee social equality? The value of the
      healthcare industry is irreplaceable, so the most critical concern is whether
      worsening doctor-patient relationships will worsen healthcare quality. In short,
      while the global budget system saves on National Health Insurance costs, whether
      its implementation has affected healthcare quality is also worth exploring. This
      commentary also hopes to serve as a reference for the implementation of national
      health insurance in the United States.

PMID- 24890572
TI  - Diarrhoeagenic microbes by real-time PCR in Rwandan children under 5 years of age
      with acute gastroenteritis.
AB  - Acute gastroenteritis is a main cause of disease and death among children in low
      income countries. The causality rates and pathogenic characteristics of putative
      aetiological agents remain insufficiently known. We used real-time PCR targeting
      16 diarrhoeagenic agents to analyse stool samples from children <=5.0 years old
      with acute diarrhoea in Rwanda. Among the 880 children (median age 14.2 months;
      41% female) at least one pathogen was detected in 92% and two or more agents in
      63% of cases. Rotavirus was detected in 36.9%, adenovirus in 39.7%,
      enterotoxigenic Escherichia coli (ETEC) with genes for labile (eltB) or stable
      (estA) toxin in 31.3% and 19.0%, E. coli with eae or bfpA genes in 25.2% and
      14.2%, Shigella in 17.5% and Cryptosporidium in 7.8%. Rotavirus and ETEC-estA
      were associated with more severe dehydration than diarrhoea due to other causes.
      Shigella was associated with bloody stools and higher CRP. Microbial loads (Ct
      values) of rotavirus, ETEC-estA and Shigella were associated with severity of
      symptoms. Rotavirus, ETEC-estA and E. coli with bfpA were associated with younger
      age, Shigella with older age. Antibiotic treatment was given to 42% and was
      associated with dehydration, fever and CRP, but not with pathogen. We conclude
      that rotavirus and ETEC-estA were the most important causes of diarrhoea with
      dehydration, that Shigella caused bloody diarrhoea but less severe dehydration,
      that microbial loads of rotavirus, ETEC-estA and Shigella were associated with
      severity of symptoms, and that antibiotic use was frequent and in poor agreement
      with microbiological findings. 

PMID- 24890573
TI  - Does a single session of Attentional Bias Modification influence early neural
      mechanisms of spatial attention? An ERP study.
AB  - A relatively new cognitive-affective training procedure, the Attentional Bias
      Modification (ABM) technique, is thought to decrease biases in the allocation of
      attention toward negative emotional stimuli. In two studies, we tested in samples
      of healthy students whether a single session of ABM has an influence on early
      orienting of spatial attention as indexed by the N2pc. Replicating previous
      studies, we found an occipitotemporal N2pc (180-300  ms) contralateral to angry
      versus neutral facial expressions, indicating that threatening faces
      automatically draw attention in early stages of stimulus processing. However,
      this N2pc effect did not significantly change during the ABM training session.
      Our results therefore indicate that a single session of ABM does not affect early
      attentional orienting. ABM effects reported in prior research may therefore have
      been mediated by later cognitive-affective mechanisms.

PMID- 24890574
TI  - Concurrent use of drugs and supplements in a community-dwelling population aged
      50 years or more: potential benefits and risks.
AB  - BACKGROUND: The use of vitamin and mineral (VMs) and non-vitamin/non-mineral
      supplements (non-VMs) in the general population and the older population in
      developed countries has increased. When combined with drugs, their use can be
      associated with benefit and potential risks. OBJECTIVE: The aims of this study
      were to determine the extent and associated factors of the combined use of drugs
      and VM/non-VM supplements, and to examine the potential major drug-supplement
      interactions METHODS: Cross-sectional analysis of first-wave data of TILDA, The
      Irish Longitudinal Study on Ageing, nationally representative a cohort including
      8,081 community-dwelling persons aged >=50 years. Prevalences including 95 %
      confidence intervals (CI) were weighted to the population. Group differences in
      drug and supplement use were assessed using Pearson's Chi-square test, and
      associations between concurrent drug-supplement use and covariates were assessed
      using logistic regression. Potential interactions between drugs and supplements
      were assessed using relevant sources. RESULTS: Every seventh respondent (14.0 %;
      95 % CI 13.1-15.0) reported regular concurrent use of drugs and supplements; 7.9
      % (95 % CI 7.3-8.6) took only VMs, 3.9 % (95 % CI 3.4-4.4) took only non-VMs, and
      2.2 % (95 % CI 1.8-2.6) took at least one of each concurrently with drugs.
      Concurrent use was more prevalent in women and in the oldest (>=75 years) group.
      Chronic disease, female sex, third-level education and private medical insurance
      were associated with an increased likelihood of use of both supplement types,
      whereas those classed as employed were much less likely to use any supplements.
      Supplements were combined with drugs in all of the commonly prescribed
      therapeutic groups, ranging from just under 60 % with drugs for bone diseases to
      15.7 % with drugs for diabetes. Potential major drug-supplement interactions were
      detected in 4.5 % (95 % CI 3.4-5.8) of concurrent drug-supplement users, and were
      more prevalent in older respondents. CONCLUSIONS: Concurrent use of drugs and
      supplements among those aged over 50 years in the Irish population is substantial
      and increases with age. There is considerable variation in usage, and the outcome
      of this approach is evidence of unmet need and therefore unrealised benefits
      among some subgroups, and of exposure to avoidable and potential serious drug
      interactions among others.

PMID- 24890575
TI  - Investigating patterns of symbiotic nitrogen fixation during vegetation change
      from grassland to woodland using fine scale delta(15) N measurements.
AB  - Biological nitrogen fixation (BNF) in woody plants is often investigated using
      foliar measurements of delta(15) N and is of particular interest in ecosystems
      experiencing increases in BNF due to woody plant encroachment. We sampled
      delta(15) N along the entire N uptake pathway including soil solution, xylem sap
      and foliage to (1) test assumptions inherent to the use of foliar delta(15) N as
      a proxy for BNF; (2) determine whether seasonal divergences occur between
      delta(15) Nxylem sap and delta(15) Nsoil inorganic N that could be used to infer
      variation in BNF; and (3) assess patterns of delta(15) N with tree age as
      indicators of shifting BNF or N cycling. Measurements of woody N-fixing Prosopis
      glandulosa and paired reference non-fixing Zanthoxylum fagara at three seasonal
      time points showed that delta(15) Nsoil inorganic N varied temporally and
      spatially between species. Fractionation between xylem and foliar delta(15) N was
      consistently opposite in direction between species and varied on average by
      2.40/00. Accounting for these sources of variation caused percent nitrogen
      derived from fixation values for Prosopis to vary by up to ~70%. Soil-xylem
      delta(15) N separation varied temporally and increased with Prosopis age,
      suggesting seasonal variation in N cycling and BNF and potential long-term
      increases in BNF not apparent through foliar sampling alone. 

PMID- 24890576
TI  - Guidelines for reporting case studies on extracorporeal treatments in poisonings:
      methodology.
AB  - A literature review performed by the EXtracorporeal TReatments In Poisoning
      (EXTRIP) workgroup highlighted deficiencies in the existing literature,
      especially the reporting of case studies. Although general reporting guidelines
      exist for case studies, there are none in the specific field of extracorporeal
      treatments in toxicology. Our goal was to construct and propose a checklist that
      systematically outlines the minimum essential items to be reported in a case
      study of poisoned patients undergoing extracorporeal treatments. Through a
      modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP
      workgroup) were asked to vote on the pertinence of a set of items to identify
      those considered minimally essential for reporting complete and accurate case
      reports. Furthermore, independent raters validated the clarity of each selected
      items between each round of voting. All case reports containing data on
      extracorporeal treatments in poisoning published in Medline in 2011 were reviewed
      during the external validation rounds. Twenty-one panelists (20 from the EXTRIP
      workgroup and an invited expert on pharmacology reporting guidelines)
      participated in the modified Delphi technique. This group included journal
      editors and experts in nephrology, clinical toxicology, critical care medicine,
      emergency medicine, and clinical pharmacology. Three independent raters
      participated in the validation rounds. Panelists voted on a total of 144 items in
      the first round and 137 items in the second round, with response rates of 96.3%
      and 98.3%, respectively. Twenty case reports were evaluated at each validation
      round and the independent raters' response rate was 99.6% and 98.8% per
      validation round. The final checklist consists of 114 items considered essential
      for case study reporting. This methodology of alternate voting and external
      validation rounds was useful in developing the first reporting guideline for case
      studies in the field of extracorporeal treatments in poisoning. We believe that
      this guideline will improve the completeness and transparency of published case
      reports and that the systematic aggregation of information from case reports may
      provide early signals of effectiveness and/or harm, thereby improving healthcare
      decision-making. 

PMID- 24890577
TI  - Intraoperative bleeding and haemostasis during pelvic surgery for locally
      advanced or recurrent rectal cancer: a prospective evaluation.
AB  - BACKGROUND: This study aimed to prospectively quantify the frequency of serious
      bleeding during pelvic surgery for locally advanced or recurrent rectal cancer
      and review the surgical methods used to control this. METHODS: Consecutive cases
      of pelvic surgery for curative resection of locally advanced or recurrent rectal
      cancer were prospectively evaluated over a nine-month period. The procedures
      undertaken included multivisceral resections, sacrectomies or ultra-low anterior
      resections. Multivisceral resections were defined as pelvic exenterations, extra
      levator abdominoperineal resections (ELAPER) and recurrent anterior resections.
      The primary endpoint was the proportion of patients sustaining major blood loss,
      defined as >=1,000 ml. The secondary endpoint was the blood transfusion rate.
      Haemostatic adjunct use was recorded. RESULTS: Twenty-six patients underwent
      surgery, comprising 11 pelvic exenterations, 3 ELAPERs, 1 recurrent anterior
      resection, 5 abdominosacral resections and 6 ultra-low anterior resections. The
      median intraoperative blood loss was 1,250 ml with 53.8 % of the patients
      sustaining a loss >=1,000 ml. Fifty per cent of patients required a blood
      transfusion within 24 h, and one or more haemostatic adjuncts were necessary in
      50 % of the cases. Adjuncts used included a fibrinogen/thrombin haemostatic agent
      in 38.5 % of patients, temporary intraoperative pelvic packing in 11.5 % of
      patients and preoperative internal iliac artery embolization in 7.7 % of
      patients. CONCLUSIONS: This patient group is at a high risk of intraoperative
      haemorrhage, and such patients are high consumers of blood products. Haemostatic
      adjunct use is often necessary to minimize blood loss. We describe our local
      algorithm to assist in the assessment and intraoperative management of these
      challenging cases.

PMID- 24890578
TI  - High-field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles
      using a non-invasive combined stimulation and force measurement device.
AB  - We have designed and constructed an experimental set-up allowing electrical
      stimulation of hindlimb mouse muscles and the corresponding force measurements at
      high-field (11.75T). We performed high-resolution multimodal MRI (including T2 
      weighted imaging, angiography and diffusion) and analysed the corresponding MRI
      changes in response to a stimulation protocol. Mice were tested twice over a 1
      week period to investigate the reliability of mechanical measurements and T2
      changes associated with the stimulation protocol. Additionally, angiographic
      images were obtained before and immediately after the stimulation protocol.
      Finally, multislice diffusion imaging was performed before, during and
      immediately after the stimulation session. Apparent diffusion coefficient (ADC)
      maps were calculated on the basis of diffusion weighted images (DWI). Both force
      production and T2 values were highly reproducible as illustrated by the low
      coefficient of variation (<8%) and high intraclass correlation coefficient
      (>=0.75) values. Maximum intensity projection angiographic images clearly showed
      a strong vascular effect resulting from the stimulation protocol. Although a
      motion sensitive imaging sequence was used (echo planar imaging) and in spite of
      the strong muscle contractions, motion artifacts were minimal for DWI recorded
      under exercising conditions, thereby underlining the robustness of the
      measurements. Mean ADC values increased under exercising conditions and were
      higher during the recovery period as compared with the corresponding control
      values. The proposed experimental approach demonstrates accurate high-field
      multimodal MRI muscle investigations at a preclinical level which is of interest
      for monitoring the severity and/or the progression of neuromuscular diseases but
      also for assessing the efficacy of potential therapeutic interventions.

PMID- 24890579
TI  - Quantitative electroencephalography biomarkers of cognitive complaints after
      adjuvant therapy in breast cancer survivors: a pilot study.

PMID- 24890581
TI  - Gestational weight change in women attending a group antenatal program aimed at
      addressing obesity in pregnancy in New South Wales, Australia.
AB  - INTRODUCTION: The prevalence of obesity in Australia among women of childbearing
      age has doubled over the past 2 decades. Obesity is associated with complications
      for women and their newborns during pregnancy and birth. Limiting gestational
      weight gain can reduce perinatal complications and postnatal weight retention,
      but evidence supporting interventions designed to assist obese pregnant women to
      manage their weight gain in pregnancy is inconclusive. The aim of this article is
      to describe the gestational weight change of a cohort of obese pregnant women
      enrolled in a group antenatal program aimed at assisting them to limit their
      weight gain in pregnancy to levels recommended by the US Institute of Medicine.
      METHODS: The program was jointly developed by 2 metropolitan maternity services
      in New South Wales, Australia. This is a descriptive study that presents select
      data for women enrolled in the program. Body mass index (BMI), prepregnancy
      weight, last pregnancy weight, and selected clinical outcomes were recorded for
      82 obese women enrolled in the program during the evaluation period of 14 months.
      Data were analyzed using nonparametric tests: the chi-square and the Mann-Whitney
      U tests. RESULTS: Parity was associated with prepregnancy BMI, with women of
      higher parity having higher BMIs. Women with higher BMIs had a significantly
      lower gestational weight gain than women with lower BMIs. Overall, 27% of women
      enrolled in the program gained the recommended 5 to 9 kg, 27% gained less than
      this amount, and 46% gained more. DISCUSSION: Evidence supporting interventions
      designed to assist obese pregnant women to manage their weight gain in pregnancy
      is lacking. This innovative, collaborative program shows promise, as early
      results compare favorably with international comparisons.

PMID- 24890582
TI  - Time-lapse embryo imaging for improving reproductive outcomes: systematic review
      and meta-analysis.
AB  - OBJECTIVE: To identify, appraise and summarize the available evidence regarding
      the effectiveness and safety of time-lapse embryo monitoring on the main outcomes
      of assisted reproductive techniques. METHODS: In this systematic review and meta
      analysis, we included only randomized controlled trials (RCTs) comparing time
      lapse embryo imaging with standard embryo monitoring. Our primary outcomes were
      live births (efficacy) and congenital abnormalities (safety). The secondary
      outcomes were clinical pregnancy, ongoing pregnancy and miscarriage. RESULTS: Two
      RCTs were considered eligible, and their data were extracted and included in a
      meta-analysis. In both studies embryos were transferred at the blastocyst stage.
      No studies reported rates of live birth or congenital abnormalities. Our
      estimates were not sufficiently precise to identify whether time-lapse monitoring
      provided a small benefit, no effect or minor harm on rates of clinical pregnancy
      (relative risk (RR), 1.05 (95% CI, 0.80-1.38)) or ongoing pregnancy (RR, 1.05
      (95% CI, 0.76-1.45)), based on two studies involving 138 women with moderate
      quality evidence. Considering the available data, we were unable to determine
      whether the intervention poses substantial benefit, no effect or substantial harm
      in the risk of miscarriage (RR, 0.95 (95% CI, 0.30-2.99)), based on two studies
      involving 76 clinical pregnancies with low-quality evidence. CONCLUSIONS: Time
      lapse embryo imaging is unlikely to have a large effect on the chance of
      achieving clinical and/or ongoing pregnancy when transferring embryos at the
      blastocyst stage. More studies are required to improve the quality of the current
      evidence and also to examine whether this intervention is useful when
      transferring embryos at the cleavage stage.

PMID- 24890584
TI  - Population-based cohort study of anti-infective medication use before and after
      the onset of type 1 diabetes in children and adolescents.
AB  - A population-based cohort study was conducted in the Dutch PHARMO database to
      investigate prevalence and patterns of anti-infective medication use in children
      and adolescents with type 1 diabetes (T1D) before and after the onset of this
      disease. All patients <19 years with at least 2 insulin prescriptions (1999 to
      2009) were identified (T1D cohort) and compared with an age- and sex-matched
      (ratio: 1 up to 4) diabetes-free reference group. The prevalence and average
      number of anti-infective use was studied from (up to) 8 years before until a
      maximum of 4 years after the onset of T1D. A total of 925 patients with T1D and
      3,591 children and adolescents in the reference cohort (51% boys, mean age of
      10.1 [standard deviation, 4.5] years) were included. The overall prevalence of
      anti-infective use (62.6 compared to 52.6%, P < 0.001) and average number of
      prescriptions (2.71 compared to 1.42 per child, P < 0.001) in the T1D cohort were
      significantly higher than those in the reference cohort after the onset of
      diabetes. This pattern was consistent across sex and age categories and already
      observed in the year before the onset of type 1 diabetes. Patients in the T1D
      cohort received more antibacterials (49.8 compared to 40%, P < 0.001),
      antimycotics (4.0 compared to 1.3%, P < 0.001), antivirals (2.5 compared to 0.4%,
      P < 0.001), and second-line antibiotics, such as aminoglycosides, quinolones, and
      third-generation cephalosporins and carbapenems. Our findings that elevated anti
      infective use in the T1D cohort exists in the period before the onset of type 1
      diabetes and the consumption of more second-line anti-infective compounds in this
      time period warrant further research. 

PMID- 24890583
TI  - Fidaxomicin inhibits Clostridium difficile toxin A-mediated enteritis in the
      mouse ileum.
AB  - Clostridium difficile infection (CDI) is a common, debilitating infection with
      high morbidity and mortality. C. difficile causes diarrhea and intestinal
      inflammation by releasing two toxins, toxin A and toxin B. The macrolide
      antibiotic fidaxomicin was recently shown to be effective in treating CDI, and
      its beneficial effect was associated with fewer recurrent infections in CDI
      patients. Since other macrolides possess anti-inflammatory properties, we
      examined the possibility that fidaxomicin alters C. difficile toxin A-induced
      ileal inflammation in mice. The ileal loops of anesthetized mice were injected
      with fidaxomicin (5, 10, or 20 MUM), and after 30 min, the loops were injected
      with purified C. difficile toxin A or phosphate-buffered saline alone. Four hours
      after toxin A administration, ileal tissues were processed for histological
      evaluation (epithelial cell damage, neutrophil infiltration, congestion, and
      edema) and cytokine measurements. C. difficile toxin A caused histologic damage,
      evidenced by increased mean histologic score and ileal interleukin-1beta (IL
      1beta) protein and mRNA expression. Treatment with fidaxomicin (20 MUM) or its
      primary metabolite, OP-1118 (120 MUM), significantly inhibited toxin A-mediated
      histologic damage and reduced the mean histology score and ileal IL-1beta protein
      and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell
      rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with
      vancomycin (20 MUM) and metronidazole (20 MUM) did not alter toxin A-induced
      histologic damage and IL-1beta protein expression. In addition to its well known
      antibacterial effects against C. difficile, fidaxomicin may possess anti
      inflammatory activity directed against the intestinal effects of C. difficile
      toxins. 

PMID- 24890585
TI  - Caspofungin at catheter lock concentrations eradicates mature biofilms of Candida
      lusitaniae and Candida guilliermondii.
AB  - The antibiofilm activities of caspofungin, anidulafungin, micafungin, and
      liposomal amphotericin B were studied against Candida lusitaniae, Candida
      guilliermondii, and a Candida albicans control strain. While anidulafungin and
      micafungin (0.007 to 2,048 mg/liter) showed reduced activity against biofilms of
      both test species, caspofungin displayed concentration-dependent antibiofilm
      activity, reaching complete and persistent eradication at concentrations
      achievable during lock therapy (512 to 2,048 mg/liter, P < 0.05). Although
      liposomal amphotericin B strongly inhibited mature biofilms, it possessed lower
      antibiofilm activity than caspofungin (P < 0.05). 

PMID- 24890586
TI  - Improved detection of emerging drug-resistant mutant cytomegalovirus
      subpopulations by deep sequencing.
AB  - In immunosuppressed hosts, the development of multidrug resistance complicates
      the treatment of cytomegalovirus (CMV) infection. Improved genotypic detection of
      impending drug resistance may follow from recent technical advances. A severely T
      cell-depleted patient with chronic lymphocytic leukemia developed CMV pneumonia
      and high plasma viral loads that were poorly responsive to antiviral therapy.
      Serial plasma specimens were analyzed for mutant viral populations by
      conventional and high-throughput deep-sequencing methods. Uncharacterized
      mutations were phenotyped for drug resistance using recombinant viruses.
      Conventional genotyping detected viruses with the UL97 kinase substitution C607Y
      after ganciclovir treatment, a transient subpopulation of UL54 polymerase L773V
      mutants first detected 8 weeks after foscarnet was started, and a subpopulation
      of a mutant with deletion of UL54 codons 981 and 982 2 months after the addition
      of cidofovir. Deep sequencing of the same serial specimens revealed the same UL54
      mutants sooner, along with a more complex evolution of known and newly recognized
      mutant subpopulations missed by conventional sequencing. The UL54 exonuclease
      substitutions D413N, K513R, and C539G were newly shown to confer ganciclovir
      cidofovir resistance, while L773V was shown to confer foscarnet resistance and
      add to the ganciclovir resistance conferred by UL97 C607Y. Increased sequencing
      depth provided a more timely and detailed diagnosis of mutant viral
      subpopulations that evolved with changing anti-CMV therapy. 

PMID- 24890587
TI  - Posaconazole concentrations in human tissues after allogeneic stem cell
      transplantation.
AB  - Few data have been published regarding posaconazole tissue concentrations in
      humans. We analyzed tissue concentrations in biopsy specimens taken at autopsy
      from seven patients who received posaconazole prophylaxis because of graft-versus
      host disease. The results were compared to plasma concentrations collected before
      death. Tissue concentrations suggestive of an accumulation of posaconazole were
      found in the heart, lung, liver, and kidney but not in the brain. 

PMID- 24890588
TI  - OXA-207, a novel OXA-24 variant with reduced catalytic efficiency against
      carbapenems in Acinetobacter pittii from Spain.
AB  - A carbapenem-resistant Acinetobacter pittii strain carrying an OXA-24-like enzyme
      was isolated in northern Spain in 2008. Sequence analysis confirmed the presence
      of the novel bla(OXA-207) gene flanked by the site-specific XerC/XerD-like
      recombination binding sites and showing a unique Gly222Val substitution compared
      to OXA-24. Cloning and kinetic analysis showed that OXA-207 presents a reduction
      in the catalytic efficiency against carbapenems and a noticeable increase for
      oxacillin.

PMID- 24890589
TI  - Linezolid-dependent function and structure adaptation of ribosomes in a
      Staphylococcus epidermidis strain exhibiting linezolid dependence.
AB  - Linezolid-dependent growth was recently reported in Staphylococcus epidermidis
      clinical strains carrying mutations associated with linezolid resistance. To
      investigate this unexpected behavior at the molecular level, we isolated active
      ribosomes from one of the linezolid-dependent strains and we compared them with
      ribosomes isolated from a wild-type strain. Both strains were grown in the
      absence and presence of linezolid. Detailed biochemical and structural analyses
      revealed essential differences in the function and structure of isolated
      ribosomes which were assembled in the presence of linezolid. The catalytic
      activity of peptidyltransferase was found to be significantly higher in the
      ribosomes derived from the linezolid-dependent strain. Interestingly, the same
      ribosomes exhibited an abnormal ribosomal subunit dissociation profile on a
      sucrose gradient in the absence of linezolid, but the profile was restored after
      treatment of the ribosomes with an excess of the antibiotic. Our study suggests
      that linezolid most likely modified the ribosomal assembly procedure, leading to
      a new functional ribosomal population active only in the presence of linezolid.
      Therefore, the higher growth rate of the partially linezolid-dependent strains
      could be attributed to the functional and structural adaptations of ribosomes to
      linezolid. 

PMID- 24890590
TI  - Studies on the antileishmanial mechanism of action of the arylimidamide DB766:
      azole interactions and role of CYP5122A1.
AB  - Arylimidamides (AIAs) are inspired by diamidine antimicrobials but show superior
      activity against intracellular parasites. The AIA DB766 {2,5-bis[2-(2-i-propoxy)
      4-(2-pyridylimino)aminophenyl]furan hydrochloride} displays outstanding potency
      against intracellular Leishmania parasites and is effective in murine and hamster
      models of visceral leishmaniasis when given orally, but its mechanism of action
      is unknown. In this study, through the use of continuous DB766 pressure, we
      raised Leishmania donovani axenic amastigotes that displayed 12-fold resistance
      to this compound. These DB766-resistant (DB766R) parasites were 2-fold more
      sensitive to miltefosine than wild-type organisms and were hypersensitive to the
      sterol 14alpha-demethylase (CYP51) inhibitors ketoconazole and posaconazole
      (2,000-fold more sensitive and over 12,000-fold more sensitive than the wild
      type, respectively). Western blot analysis of DB766R parasites indicated that
      while expression of CYP51 is slightly increased in these organisms, expression of
      CYP5122A1, a recently identified cytochrome P450 associated with ergosterol
      metabolism in Leishmania, is dramatically reduced in DB766R parasites. In vitro
      susceptibility assays demonstrated that CYP5122A1 half-knockout L. donovani
      promastigotes were significantly less susceptible to DB766 and more susceptible
      to ketoconazole than their wild-type counterparts, consistent with observations
      in DB766R parasites. Further, DB766-posaconazole combinations displayed
      synergistic activity in both axenic and intracellular L. donovani amastigotes.
      Taken together, these studies implicate CYP5122A1 in the antileishmanial action
      of the AIAs and suggest that DB766-azole combinations are potential candidates
      for the development of synergistic antileishmanial therapy. 

PMID- 24890591
TI  - Complete sequencing of IncI1 sequence type 2 plasmid pJIE512b indicates
      mobilization of blaCMY-2 from an IncA/C plasmid.
AB  - Sequencing of pJIE512b, a 92.3-kb IncI1 sequence type 2 (ST2) plasmid carrying
      bla(CMY-2), revealed a bla(CMY-2) context that appeared to have been mobilized
      from an IncA/C plasmid by the insertion sequence IS1294. A comparison with
      published plasmids suggests that bla(CMY-2) has been mobilized from IncA/C to
      IncI1 plasmids more than once by IS1294-like elements. Alignment of pJIE512b with
      the only other available IncI1 ST2 plasmid revealed differences across the
      backbones, indicating variability within this sequence type.

PMID- 24890592
TI  - Role of FKS Mutations in Candida glabrata: MIC values, echinocandin resistance,
      and multidrug resistance.
AB  - Candida glabrata is the second leading cause of candidemia in U.S. hospitals.
      Current guidelines suggest that an echinocandin be used as the primary therapy
      for the treatment of C. glabrata disease due to the high rate of resistance to
      fluconazole. Recent case reports indicate that C. glabrata resistance to
      echinocandins may be increasing. We performed susceptibility testing on 1,380
      isolates of C. glabrata collected between 2008 and 2013 from four U.S. cities,
      Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%,
      and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and
      micafungin, respectively. We screened 1,032 of these isolates, including all 77
      that had either a resistant or intermediate MIC value with respect to at least
      one echinocandin, for mutations in the hot spot regions of FKS1 and FKS2, the
      major mechanism of echinocandin resistance. Fifty-one isolates were identified
      with hot spot mutations, 16 in FKS1 and 35 in FKS2. All of the isolates with an
      FKS mutation except one were resistant to at least one echinocandin by
      susceptibility testing. Of the isolates resistant to at least one echinocandin,
      36% were also resistant to fluconazole. Echinocandin resistance among U.S. C.
      glabrata isolates is a concern, especially in light of the fact that one-third of
      those isolates may be multidrug resistant. Further monitoring of U.S. C. glabrata
      isolates for echinocandin resistance is warranted. 

PMID- 24890593
TI  - Antimycobacterial drugs modulate immunopathogenic matrix metalloproteinases in a
      cellular model of pulmonary tuberculosis.
AB  - Tuberculosis is characterized by extensive destruction and remodelling of the
      pulmonary extracellular matrix. Stromal cell-derived matrix metalloproteinases
      (MMPs) are implicated in this process and may be a target for adjunctive
      immunotherapy. We hypothesized that MMPs are elevated in bronchoalveolar lavage
      fluid of tuberculosis patients and that antimycobacterial agents may have a
      modulatory effect on MMP secretion. Concentrations of MMP-1, -2, -3, -7, -8, and 
      9 were elevated in the bronchoalveolar lavage fluid from tuberculosis patients
      compared to those in bronchoalveolar lavage fluid from patients with other
      pulmonary conditions. There was a positive correlation between MMP-3, MMP-7, and
      MMP-8 and a chest radiological score of cavitation and parenchymal damage.
      Respiratory epithelial cell-derived MMP-3 was suppressed by moxifloxacin,
      rifampicin, and azithromycin in a dose-dependent manner. Respiratory epithelial
      cell-derived MMP-1 was suppressed by moxifloxacin and azithromycin, whereas MMP-9
      secretion was only decreased by moxifloxacin. In contrast, moxifloxacin and
      azithromycin both increased MMP-1 and -3 secretion from MRC-5 fibroblasts,
      demonstrating that the effects of these drugs are cell specific. Isoniazid did
      not affect MMP secretion. In conclusion, MMPs are elevated in bronchoalveolar
      lavage fluid from tuberculosis patients and correlate with parameters of tissue
      destruction. Antimycobacterial agents have a hitherto-undescribed
      immunomodulatory effect on MMP release by stromal cells. 

PMID- 24890594
TI  - Risk factors and outcomes for patients with bloodstream infection due to
      Acinetobacter baumannii-calcoaceticus complex.
AB  - Identifying patients at risk for bloodstream infection (BSI) due to Acinetobacter
      baumannii-Acinetobacter calcoaceticus complex (ABC) and providing early
      appropriate therapy are critical for improving patient outcomes. A retrospective
      matched case-control study was conducted to investigate the risk factors for BSI
      due to ABC in patients admitted to the Detroit Medical Center (DMC) between
      January 2006 and April 2009. The cases were patients with BSI due to ABC; the
      controls were patients not infected with ABC. Potential risk factors were
      collected 30 days prior to the ABC-positive culture date for the cases and 30
      days prior to admission for the controls. A total of 245 case patients were
      matched with 245 control patients. Independent risk factors associated with BSI
      due to ABC included a Charlson's comorbidity score of >= 3 (odds ratio [OR],
      2.34; P = 0.001), a direct admission from another health care facility (OR, 4.63;
      P < 0.0001), a prior hospitalization (OR, 3.11; P < 0.0001), the presence of an
      indwelling central venous line (OR, 2.75; P = 0.011), the receipt of total
      parenteral nutrition (OR, 21.2; P < 0.0001), the prior receipt of beta-lactams
      (OR, 3.58; P < 0.0001), the prior receipt of carbapenems (OR, 3.18; P = 0.006),
      and the prior receipt of chemotherapy (OR, 15.42; P < 0.0001). The median time
      from the ABC-positive culture date to the initiation of the appropriate
      antimicrobial therapy was 2 days (interquartile range [IQR], 1 to 3 days). The in
      hospital mortality rate was significantly higher among case patients than among
      control patients (OR, 3.40; P < 0.0001). BSIs due to ABC are more common among
      critically ill and debilitated institutionalized patients, who are heavily
      exposed to health care settings and invasive devices.

PMID- 24890595
TI  - Characterization of a novel Neisseria gonorrhoeae penicillinase-producing plasmid
      isolated in Australia in 2012.

PMID- 24890596
TI  - Evaluation of vancomycin population susceptibility analysis profile as a
      predictor of outcomes for patients with infective endocarditis due to methicillin
      resistant Staphylococcus aureus.
AB  - Infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA
      IE) is associated with high morbidity and mortality. Vancomycin continues to be
      the primary treatment for this disease. The emergence of heterogeneous vancomycin
      intermediate Staphylococcus aureus (hVISA), defined as a modified population
      analysis profile (PAP) of >= 0.9, may affect patient outcomes. The objective of
      this study was to evaluate the relationship of vancomycin subpopulation
      susceptibility and the clinical outcomes of MRSA IE. We conducted a retrospective
      cohort study of patients treated with vancomycin for MRSA IE from 2002 to 2013 at
      the Detroit Medical Center. A modified PAP was used to measure the vancomycin PAP
      MIC and the PAP-to-area under the curve (AUC) ratio. Treatment failure was
      defined as bacteremia for >= 7 days or death attributed to MRSA. Classification
      and regression tree (CART) analysis was used to select a failure breakpoint
      between the PAP-AUC ratios and the PAP MIC. A total of 202 patients were included
      in the study. Twenty-seven percent of the patients had left-sided IE, 19% of the
      strains were hVISA, and 70% of the strains were staphylococcal cassette
      chromosome mec element (SCCmec) type IV. Overall treatment failure was observed
      in 64%; 59% had persistent bacteremia, and the 30-day attributable mortality rate
      was 21%. The CART breakpoint between failure and success in terms of the PAP-AUC
      ratio was 0.9035. On logistic regression analysis, intensive care unit (ICU)
      admission (adjusted odds ratio [aOR], 2.8; 95% confidence interval [CI], 1.5 to
      5.2) and a PAP MIC of >= 4 mg/liter (aOR, 3.2; 95% CI, 1.3 to 8.4) were
      associated with failure (P = 0.001 and 0.015, respectively). A PAP MIC of >= 4
      mg/liter and ICU admission were significant for treatment failure for patients
      with MRSA IE. The PAP-AUC ratio of >= 0.9035 predicted failure consistent with
      the hVISA definition. The role of population MIC analysis in predicting outcome
      with MRSA infections warrants further investigation.

PMID- 24890597
TI  - The enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti
      norovirus activity and clears cells from the norovirus replicon.
AB  - Potent and safe inhibitors of norovirus replication are needed for the treatment
      and prophylaxis of norovirus infections. We here report that the in vitro anti
      norovirus activity of the protease inhibitor rupintrivir is extended to murine
      noroviruses and that rupintrivir clears human cells from their Norwalk replicon
      after only two passages of antiviral pressure. In addition, we demonstrate that
      rupintrivir inhibits the human norovirus (genogroup II [GII]) protease and
      further explain the inhibitory effect of the molecule by means of molecular
      modeling on the basis of the crystal structure of the Norwalk virus protease. The
      combination of rupintrivir with the RNA-dependent RNA polymerase inhibitors 2'-C
      methylcytidine and favipiravir (T-705) resulted in a merely additive antiviral
      effect. The fact that rupintrivir is active against noroviruses belonging to
      genogroup I (Norwalk virus), genogroup V (murine norovirus), and the recombinant
      3C-like protease of a GII norovirus suggests that the drug exerts cross-genotypic
      anti-norovirus activity and will thus most likely be effective against the
      clinically relevant human norovirus strains. The design of antiviral molecules
      targeting the norovirus protease could be a valuable approach for the treatment
      and/or prophylaxis of norovirus infections. 

PMID- 24890598
TI  - Intravitreal injection of the chimeric phage endolysin Ply187 protects mice from
      Staphylococcus aureus endophthalmitis.
AB  - The treatment of endophthalmitis is becoming very challenging due to the
      emergence of multidrug-resistant bacteria. Hence, the development of novel
      therapeutic alternatives for ocular use is essential. Here, we evaluated the
      therapeutic potential of Ply187AN-KSH3b, a chimeric phage endolysin derived from
      the Ply187 prophage, in a mouse model of Staphylococcus aureus endophthalmitis.
      Our data showed that the chimeric Ply187 endolysin exhibited strong antimicrobial
      activity against both methicillin-sensitive S. aureus and methicillin-resistant
      S. aureus (MRSA) strains, as evidenced by MIC determinations, reductions in
      turbidity, and disruption of biofilms. Moreover, exposure of S. aureus to Ply187
      for up to 10 generations did not lead to resistance development. The intravitreal
      injection of chimeric Ply187 (at 6 or 12 h postinfection) significantly improved
      the outcome of endophthalmitis, preserved retinal structural integrity, and
      maintained visual function as assessed by electroretinogram analysis.
      Furthermore, phage lysin treatment significantly reduced the bacterial burden and
      the levels of inflammatory cytokines and neutrophil infiltration in the eyes.
      These results indicate that the intravitreal administration of a phage lytic
      enzyme attenuates the development of bacterial endophthalmitis in mice. To the
      best of our knowledge, this is the first study demonstrating the therapeutic use
      of phage-based antimicrobials in ocular infections. 

PMID- 24890601
TI  - Genetic population structure of spotted seatrout Cynoscion nebulosus along the
      south-eastern U.S.A.
AB  - Analyses of the genetic population structure of spotted seatrout Cynoscion
      nebulosus along the south-eastern U.S. coast using 13 microsatellites suggest
      significant population differentiation between fish in North Carolina (NC)
      compared with South Carolina (SC) and Georgia (GA), with New River, NC, serving
      as an area of integration between northern and southern C. nebulosus. Although
      there is a significant break in gene flow between these areas, the overall
      pattern throughout the sampling range represents a gradient in genetic
      diversification with the degree of geographic separation. Latitudinal distance
      and estuarine density appear to be main drivers in the genetic differentiation of
      C. nebulosus along the south-eastern U.S. coast. The isolation-by-distance gene
      flow pattern creates fine-scale differences in the genetic composition of
      proximal estuaries and dictates that stocking must be confined to within 100 km
      of the location of broodstock collection in order to maintain the natural
      gradient of genetic variation along the south-eastern U.S. coast. 

PMID- 24890600
TI  - Metabolic drug-drug interaction potential of macrolactin A and 7-O-succinyl
      macrolactin A assessed by evaluating cytochrome P450 inhibition and induction and
      UDP-glucuronosyltransferase inhibition in vitro.
AB  - Macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides
      containing a 24-membered lactone ring, show antibiotic effects superior to those
      of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant
      Staphylococcus aureus. MA and SMA are currently being evaluated as antitumor
      agents in preclinical studies in Korea. We evaluated the potential of MA and SMA
      for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and
      UDP-glucuronosyltransferases (UGTs) in vitro to assess their safety as new
      molecular entities. We demonstrated that MA and SMA are potent competitive
      inhibitors of CYP2C9, with Ki values of 4.06 MUM and 10.6 MUM, respectively. MA
      and SMA also weakly inhibited UGT1A1 activity, with Ki values of 40.1 MUM and
      65.3 MUM, respectively. However, these macrolactins showed no time-dependent
      inactivation of the nine CYPs studied. In addition, MA and SMA did not induce
      CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an in vitro-in vivo extrapolation,
      our data strongly suggested that MA and SMA are unlikely to cause clinically
      significant drug-drug interactions mediated via inhibition or induction of most
      of the CYPs involved in drug metabolism in vivo, except for the inhibition of
      CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of
      UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes in vivo. Although further
      investigations will be required to clarify the in vivo interactions of MA with
      CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction
      of drug-drug interactions for the safe use of MA and SMA in clinical practice. 

PMID- 24890602
TI  - Development of cultured dermal substitute composed of hyaluronic acid and
      collagen spongy sheet containing fibroblasts and epidermal growth factor.
AB  - The present study aimed to develop a two-layered cultured dermal substitute
      (CDS). The upper layer is a hyaluronic acid (HA) and collagen (Col) spongy sheet
      with or without epidermal growth factor (EGF). The lower layer is a HA spongy
      sheet and Col gel containing fibroblasts. The CDS is prepared in serum-free
      medium, followed by placing on the wound surface. Corresponding to clinical
      application, CDS was incubated in serum-free medium for a period of 1, 3 or 5
      days, followed by placing onto the air and culture medium interface (wound
      surface model), and culture for 6 days using conventional culture medium
      supplemented with serum. Metabolic activity and cytokine production were
      considerably higher in EGF-incorporating CDS, as compared with EGF-free CDS.
      Metabolic activity of EGF-incorporating CDS was maintained for a period of 3
      days, but decreased slightly after 5 days. EGF-incorporating CDS is able to
      effectively stimulate fibroblasts within CDS to release increased amounts of
      vascular endothelial growth factor and hepatocyte growth factor, which are
      essential for wound healing. CDS is promising for wound therapy, because there is
      no risk of cellular damage caused by cryopreservation, thawing and rinsing
      processes. The critical issue is how to reduce the cellular damage during a
      prolonged period of incubation in serum-free medium. EGF-incorporating CDS can be
      used after a period of 3-5 days incubation in serum-free medium. This period is
      sufficient for transport of CDS from manufacturing facilities to hospitals.

PMID- 24890599
TI  - Preclinical studies of amixicile, a systemic therapeutic developed for treatment
      of Clostridium difficile infections that also shows efficacy against Helicobacter
      pylori.
AB  - Amixicile shows efficacy in the treatment of Clostridium difficile infections
      (CDI) in a mouse model, with no recurrence of CDI. Since amixicile selectively
      inhibits the action of a B vitamin (thiamine pyrophosphate) cofactor of
      pyruvate:ferredoxin oxidoreductase (PFOR), it may both escape mutation-based drug
      resistance and spare beneficial probiotic gut bacteria that do not express this
      enzyme. Amixicile is a water-soluble derivative of nitazoxanide (NTZ), an
      antiparasitic therapeutic that also shows efficacy against CDI in humans. In
      comparative studies, amixicile showed no toxicity to hepatocytes at 200 MUM (NTZ
      was toxic above 10 MUM); was not metabolized by human, dog, or rat liver
      microsomes; showed equivalence or superiority to NTZ in cytochrome P450 assays;
      and did not activate efflux pumps (breast cancer resistance protein, P
      glycoprotein). A maximum dose (300 mg/kg) of amixicile given by the oral or
      intraperitoneal route was well tolerated by mice and rats. Plasma exposure (rats)
      based on the area under the plasma concentration-time curve was 79.3 h . MUg/ml
      (30 mg/kg dose) to 328 h . MUg/ml (100 mg/kg dose), the maximum concentration of
      the drug in serum was 20 MUg/ml, the time to the maximum concentration of the
      drug in serum was 0.5 to 1 h, and the half-life was 5.6 h. Amixicile did not
      concentrate in mouse feces or adversely affect gut populations of Bacteroides
      species, Firmicutes, segmented filamentous bacteria, or Lactobacillus species.
      Systemic bioavailability was demonstrated through eradication of Helicobacter
      pylori in a mouse infection model. In summary, the efficacy of amixicile in
      treating CDI and other infections, together with low toxicity, an absence of
      mutation-based drug resistance, and excellent drug metabolism and pharmacokinetic
      metrics, suggests a potential for broad application in the treatment of
      infections caused by PFOR-expressing microbial pathogens in addition to CDI. 

PMID- 24890603
TI  - Subclinical infection without encephalitis in mice following intranasal exposure
      to Nipah virus-Malaysia and Nipah virus-Bangladesh.
AB  - BACKGROUND: Nipah virus and Hendra virus are closely related and following
      natural or experimental exposure induce similar clinical disease. In humans,
      encephalitis is the most serious outcome of infection and, hitherto, research
      into the pathogenesis of henipavirus encephalitis has been limited by the lack of
      a suitable model. Recently we reported a wild-type mouse model of Hendra virus
      (HeV) encephalitis that should facilitate detailed investigations of its
      neuropathogenesis, including mechanisms of disease recrudescence. In this study
      we investigated the possibility of developing a similar model of Nipah virus
      encephalitis. FINDINGS: Aged and young adult wild type mice did not develop
      clinical disease including encephalitis following intranasal exposure to either
      the Malaysia (NiV-MY) or Bangladesh (NiV-BD) strains of Nipah virus. However
      viral RNA was detected in lung tissue of mice at euthanasia (21 days following
      exposure) accompanied by a non-neutralizing antibody response. In a subsequent
      time course trial this viral RNA was shown to be reflective of an earlier self
      limiting and subclinical lower respiratory tract infection through successful
      virus re-isolation and antigen detection in lung. There was no evidence for
      viremia or infection of other organs, including brain. CONCLUSIONS: Mice develop
      a subclinical self-limiting lower respiratory tract infection but not
      encephalitis following intranasal exposure to NiV-BD or NiV-MY. These results
      contrast with those reported for HeV under similar exposure conditions in mice,
      demonstrating a significant biological difference in host clinical response to
      exposure with these viruses. This finding provides a new platform from which to
      explore the viral and/or host factors that determine the neuroinvasive ability of
      henipaviruses.

PMID- 24890604
TI  - The effect of habitat on modern shark diversification.
AB  - Sharks occupy marine habitats ranging from shallow, inshore environments to
      pelagic, and deepwaters, and thus provide a model system for testing how gross
      habitat differences have shaped vertebrate macroevolution. Palaeontological
      studies have shown that onshore lineages diversify more quickly than offshore
      taxa. Among onshore habitats, coral reef-association has been shown to increase
      speciation rates in several groups of fishes and invertebrates. In this study, we
      investigated whether speciation rates are habitat dependent by generating the
      first comprehensive molecular timescale for shark divergence. Using phylogenetic
      comparative methods, we rejected the hypothesis that shelf (i.e. onshore)
      lineages have higher speciation rates compared to those occupying deepwater and
      oceanic (i.e. offshore) habitats. Our results, however, support the hypothesis of
      increased speciation rates in coral reef-associated lineages within the
      Carcharhinidae. Our new timetree suggests that the two major shark lineages
      leading to the extant shark diversity began diversifying mostly after the end
      Permian mass extinction: the squalimorphs into deepwater and the galeomorphs into
      shelf habitats. We suggest that the breakdown of the onshore-offshore speciation
      rate pattern in sharks is mediated by success in deepwater environments through
      ecological partitioning, and in some cases, the evolution of morphological
      novelty. 

PMID- 24890606
TI  - Clinical outcomes following selection of human preimplantation embryos with time
      lapse monitoring: a systematic review.
AB  - BACKGROUND: Time-lapse monitoring (TLM) has emerged as a novel technology to
      perform semi-quantitative evaluation of embryo morphology and developmental
      kinetics in assisted reproduction. While this method has already been introduced
      into clinical practice in many laboratories, it is unclear whether it adds value
      to conventional morphology. Most studies only report blastocyst formation as the
      primary end-point. The aim of this systematic review is to provide a critical
      evaluation of the available studies that report clinical outcomes following
      embryo selection with TLM. METHODS: A literature search in MEDLINE, Cochrane
      CENTRAL and ISI Web of Knowledge Science Citation Index was performed to identify
      studies that assess the clinical utility of kinetic markers for non-invasive
      selection of human embryos with high implantation potential. Only studies
      published before 31 December 2013 in the English language that report rates of
      implantation, clinical pregnancy or live birth were included. RESULTS: Two
      hundred and fifty-one studies were identified by database search and reference
      list review; only 13 met eligibility criteria and were included in this analysis.
      The following morphokinetic parameters were assessed: pronuclear dynamics and
      morphology (n = 3), duration of first cytokinesis and reappearance of nuclei
      after cleavage (n = 3), time to various cleavage stages (n = 5), duration of
      various cleavage stages (n = 6), duration of cleavage cycles and mitotic
      synchronicity (n = 6), and time to morula, blastocyst and hatching (n = 4). Five
      studies used combined parameter grading to generate a cumulative score, and two
      studies retrospectively compared implantation rates following embryo selection by
      conventional morphology alone or with the addition of a hierarchal time-lapse
      classification. While several studies suggest higher implantation rates for fast
      cleaving embryos and those with a timely duration (i.e. all time points within
      the defined ranges) of the 2-cell and 3-cell stages, no single morphokinetic
      parameter has been consistently shown to predict implantation potential.
      Furthermore, there was considerable disagreement regarding not only which
      parameters are useful, but also what constitutes normal and abnormal intervals
      for these measurements. CONCLUSIONS: While TLM has the potential to revolutionize
      clinical embryology, there are currently no high-quality data to support the
      clinical use of this technology for selection of human preimplantation embryos.
      Our recommendations for the adoption of this technique are thus limited by the
      available literature and the lack of robust prospective studies reporting
      clinical outcomes. Sparse, often incomplete and largely heterogeneous data
      suggest that TLM may be able to distinguish between high and low-implantation
      potential embryos. Only one study demonstrated significantly improved clinical
      pregnancy rates when embryos were selected by TLM in addition to conventional
      morphology. Prospective studies are currently underway and hopefully will clarify
      the role of TLM. As more data become available, it is of the utmost importance
      that groups using TLM share a common nomenclature for measured time points;
      herein, we have proposed a standardized system for describing any milestone along
      the preimplantation developmental timeline. Furthermore, future studies must
      publish complete datasets in an effort to define patient-specific algorithms with
      the clinically meaningful end-point of implantation, prior to routine adoption in
      the assisted reproduction technology laboratory. Until such evidence accumulates,
      selection of embryos by TLM should remain an experimental strategy subject to
      institutional review and approval.

PMID- 24890607
TI  - Systematization, description, and territory of the caudal cerebral artery in
      surface of the brain of the ostrich (Struthio camelus).
AB  - Brain specimens from 30 ostriches were injected with red-dyed latex via the
      internal carotid arteries, and the caudal cerebral arteries and their branches
      were systematically described. On the right side, the caudal cerebral artery was
      double-, triple-, quadruple-, and single-branched in 73.5%, 23.3%, 3.3%, and 3.3%
      of cases, respectively; on the left side, it was double-, triple-, quadruple-,
      and single-branched in 76.7%, 20%, 3.3%, and 3.3% of cases, respectively. The
      dorsal tectal mesencephalic artery appeared as a single vessel in 96.7% of cases,
      emerging as a collateral branch of the caudal cerebral artery. The dorsal
      mesencephalic tectal artery originated from the right dorsal cerebellar artery in
      40% of cases and from the left side in 63.3% of cases. On the right side, there
      were four and three medial occipital hemispheric branches in 46.7% and 20% of
      cases, respectively; on the left side, there were four and three branches in 30%
      and 26.7% of cases. On the right side, the pineal artery was double-, single-,
      triple-, and quadruple-branched in 50%, 23.3%, 20%, and 6.7% of cases,
      respectively; on the left side, this artery was double-, single-, triple-, and
      quadruple-branched in 50%, 23.3%, 16.7%, and 10% of cases, respectively. The
      diencephalic artery was on the right side in 43.3% of cases and on the left side
      in 56.7% of cases. The interhemispheric artery was on the right side in 56.7% of
      cases and on the left side in 43.3% of cases; four, three, two, five, and one
      dorsal hemispheric trunks branched off of the interhemispheric artery in 40%,
      40%, 10%, 6.7%, and 26.7% of cases, respectively. The caudal cerebral artery was
      classified as Type I in 56.7% of cases (subtype IA in 33.3% of cases and IB in
      23.3% of cases), Type II in 40% of cases (subtype IIA in 20% of cases and IIB in
      20% of cases), and Type III in 3.3% of cases.

PMID- 24890609
TI  - The odd sibling: features of beta3-adrenoceptor pharmacology.
AB  - beta3-Adrenoceptor agonists have recently been introduced for the treatment of
      overactive urinary bladder syndrome. Their target, the beta3-adrenoceptor, was
      discovered much later than beta1- and beta2-adrenoceptors and exhibits unique
      properties which make extrapolation of findings from the other two subtypes
      difficult and the beta3-adrenoceptor a less-understood subtype. This article
      discusses three aspects of beta3-adrenoceptor pharmacology. First, the ligand
      recognition profile of beta3-adrenoceptors differs considerably from that of the
      other two subtypes, i.e., many antagonists considered as nonselective actually
      are beta3-sparing, including propranolol or nadolol. Many agonists and
      antagonists classically considered as being beta3-selective actually are not,
      including BRL 37,344 ((+/-)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2
      hydroxyethyl]amino]propyl]phenoxy] acetic acid sodium hydrate) or SR 59,230 (3-(2
      ethylphenoxy)-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol oxalate).
      Moreover, the binding pocket apparently differs between the human and rodent
      beta3-adrenoceptor, yielding considerable species differences in potency. Second,
      the expression pattern of beta3-adrenoceptors is more restricted than that of
      other subtypes, particularly in humans; this makes extrapolation of rodent
      findings to the human situation difficult, but it may result in a smaller
      potential for side effects. The role of beta3-adrenoceptor gene polymorphisms has
      insufficiently been explored and may differ even between primate species. Third,
      beta3-adrenoceptors lack the phosphorylation sites involved in agonist-induced
      desensitization of the other two subtypes. Thus, they exhibit downregulation
      and/or desensitization in some, but not other, cell types and tissues. When
      desensitization occurs, it most often is at the level of mRNA or signaling
      molecule expression. All three of these factors have implications for future
      studies to better understand the beta3-adrenoceptor as a novel pharmacological
      target. 

PMID- 24890610
TI  - Indole synthesis based on a modified Koser reagent.
AB  - A new metal-free method for the rapid and productive preparation of indoles has
      been developed. This process is based on sterically congested hypervalent iodine
      compounds of the family of Koser reagents, and iodosobenzene in combination with
      2,4,5-tris-isopropylbenzene sulfonic acid provides the highest yields and fastest
      reaction times. This reagent alone promotes the chemoselective oxidative
      cyclization of 2-amino styrenes to indoles in high yields under mild conditions. 

PMID- 24890608
TI  - Poisoning of mitochondrial topoisomerase I by lamellarin D.
AB  - Lamellarin D (Lam-D) is a hexacyclic pyrole alkaloid isolated from marine
      invertebrates, whose biologic properties have been attributed to mitochondrial
      targeting. Mitochondria contain their own DNA (mtDNA), and the only specific
      mitochondrial topoisomerase in vertebrates is mitochondrial topoisomerase I
      (Top1mt). Here, we show that Top1mt is a direct mitochondrial target of Lam-D. In
      vitro Lam-D traps Top1mt and induces Top1mt cleavage complexes (Top1mtcc). Using
      single-molecule analyses, we also show that Lam-D slows down supercoil relaxation
      of Top1mt and strongly inhibits Top1mt religation in contrast to the inefficacy
      of camptothecin on Top1mt. In living cells, we show that Lam-D accumulates
      rapidly inside mitochondria, induces cellular Top1mtcc, and leads to mtDNA
      damage. This study provides evidence that Top1mt is a direct mitochondrial target
      of Lam-D and suggests that developing Top1mt inhibitors represents a novel
      strategy for targeting mitochondrial DNA. 

PMID- 24890611
TI  - Optimized plasmid systems for the incorporation of multiple different unnatural
      amino acids by evolved orthogonal ribosomes.
AB  - Incorporation of multiple different unnatural amino acids into the same
      polypeptide remains a significant challenge. Orthogonal ribosomes, which are
      evolvable as they direct the translation of a single dedicated orthogonal mRNA,
      can provide an avenue to produce such polypeptides routinely. Recent advances in
      engineering orthogonal ribosomes have created a prototype system to enable
      genetically encoded introduction of two different functional groups, albeit with
      limited efficiency. Here, we systematically investigated the limiting factors of
      this system by using assays to measure the levels and activities of individual
      components; we identified Methanosarcina barkeri PylRS as a limiting factor for
      protein yield. Balancing the expression levels of individual components
      significantly improved growth rate and protein yield. This optimization of the
      system is likely to increase the scope of evolved orthogonal ribosome-mediated
      incorporation of multiple different unnatural amino acids. 

PMID- 24890613
TI  - Reduced BMP6 expression by DNA methylation contributes to EMT and drug resistance
      in breast cancer cells.
AB  - Bone morphogenetic protein 6 (BMP6) is an important regulator of cell growth,
      differentiation and apoptosis in various types of tumor. In breast cancer, it was
      considered as a tumor suppressor. Our previous study also confirmed that BMP6 was
      a critical regulator of breast cancer drug resistance. However, little is known
      about how its expression is regulated and its mechanisms in breast cancer drug
      resistance. In the present study, we assessed the DNA methylation regulation of
      BMP6 based on the presence of a large CpG island in the BMP6 gene promoter.
      Quantitative DNA methylation analyses showed a significantly increased DNA
      methylation level in the drug-resistant cell line MCF-7/ADR compared to their
      parental cells MCF-7. Moreover, the drug-resistant cell line MCF-7/ADR showed an
      EMT phenotype confirmed by morphology and the expression of EMT marker gene. MCF
      7 cells transfected with BMP6-specific shRNA vector also showed an EMT phenotype.
      The MCF-7/ADR cells treated with the recombinant BMP6 proteins reversed their EMT
      phenotype. These data indicated that hypermethylation modifications contributed
      to the regulation of BMP6 and induced an EMT phenotype of breast cancer during
      the acquisition of drug resistance.

PMID- 24890614
TI  - Vegetation productivity patterns at high northern latitudes: a multi-sensor
      satellite data assessment.
AB  - Satellite-derived indices of photosynthetic activity are the primary data source
      used to study changes in global vegetation productivity over recent decades.
      Creating coherent, long-term records of vegetation activity from legacy satellite
      data sets requires addressing many factors that introduce uncertainties into
      vegetation index time series. We compared long-term changes in vegetation
      productivity at high northern latitudes (>50 degrees N), estimated as trends in
      growing season NDVI derived from the most widely used global NDVI data sets. The
      comparison included the AVHRR-based GIMMS-NDVI version G (GIMMSg ) series, and
      its recent successor version 3g (GIMMS3g ), as well as the shorter NDVI records
      generated from the more modern sensors, SeaWiFS, SPOT-VGT, and MODIS. The data
      sets from the latter two sensors were provided in a form that reduces the effects
      of surface reflectance associated with solar and view angles. Our analysis
      revealed large geographic areas, totaling 40% of the study area, where all data
      sets indicated similar changes in vegetation productivity over their common
      temporal record, as well as areas where data sets showed conflicting patterns.
      The newer, GIMMS3g data set showed statistically significant (alpha = 0.05)
      increases in vegetation productivity (greening) in over 15% of the study area,
      not seen in its predecessor (GIMMSg ), whereas the reverse was rare (<3%). The
      latter has implications for earlier reports on changes in vegetation activity
      based on GIMMSg , particularly in Eurasia where greening is especially pronounced
      in the GIMMS3g data. Our findings highlight both critical uncertainties and areas
      of confidence in the assessment of ecosystem-response to climate change using
      satellite-derived indices of photosynthetic activity. Broader efforts are
      required to evaluate NDVI time series against field measurements of vegetation
      growth, primary productivity, recruitment, mortality, and other biological
      processes in order to better understand ecosystem responses to environmental
      change over large areas.

PMID- 24890615
TI  - Experiences of patients with borderline personality disorder with the brief
      admission intervention: a phenomenological study.
AB  - Brief admission is a crisis intervention for patients with borderline personality
      disorder (BPD), and refers to a clinical admission at a psychiatric hospital for
      a period of 1-5 nights. Patients formulate a treatment plan together with their
      community mental health nurse about the maximum frequency allowed for these brief
      admissions. The purpose of the study was to describe the lived experiences of
      patients with BPD with use of the brief admission intervention. The study used a
      phenomenological approach. Inclusion criteria were a diagnosis of BPD, according
      to the Diagnostic and Statistical Manual of Mental Disorders-IV criteria;
      experience with brief admission, and sufficient understanding of the Dutch
      language. A total of 16 female patients and one male patient participated in the
      study. Thematic analysis of the transcripts of the interviews revealed four major
      meaning units: (i) organization of the brief admission; (ii) contact with a
      nurse; (iii) time out from daily life; and (iv) experienced value for the
      patient. Patients highlighted the quality of the contact with a nurse as the most
      important aspect of the brief admission. Nurses should be aware of the importance
      of connecting with patients who have BPD during a brief admission, particularly
      in light of the interpersonal hypersensitivity that characterizes these patients.

PMID- 24890612
TI  - Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic
      accomplice?
AB  - Harbored as relics of ancient germline infections, human endogenous retroviruses
      (HERVs) now constitute up to 8% of our genome. A proportion of this sequence has
      been co-opted for molecular and cellular processes, beneficial to human
      physiology, such as the fusogenic activity of the envelope protein, a vital
      component of placentogenesis. However, the discovery of high levels of HERV-K
      mRNA and protein and even virions in a wide array of cancers has revealed that
      HERV-K may be playing a more sinister role-a role as an etiological agent in
      cancer itself. Whether the presence of this retroviral material is simply an
      epiphenomenon, or an actual causative factor, is a hotly debated topic. This
      review will summarize the current state of knowledge regarding HERV-K and cancer
      and attempt to outline the potential mechanisms by which HERV-K could be involved
      in the onset and promotion of carcinogenesis. 

PMID- 24890616
TI  - Differential sensitization of silent nociceptors to low pH stimulation by
      prostaglandin E2 in human volunteers.
AB  - BACKGROUND: Inflammatory mediators activate and sensitize nociceptors. Tissue
      acidosis with low pH of 5.5 often accompanies inflammation and could enhance
      inflammatory pain and sensitization. METHODS: Action potentials from single
      mechano-responsive (CM) and mechano-insensitive (CMi) C-nociceptors of cutaneous
      fascicles of the peroneal nerve in healthy volunteers were recorded by
      microneurography. Low pH solutions with and without prostaglandin E2 (PGE2) were
      injected twice (with an interval of approximately 5 min) into two spots of the
      receptive fields of C-fibres. Heat thresholds of the C-fibres were obtained
      before and after each injection. RESULTS: Injections of the low pH solutions
      immediately induced phasic responses in CM nociceptors, whereas CMi fibres
      responded after a delay of several seconds with a sustained response. More CMi
      fibres than CM fibres showed ongoing discharge after low pH injection, but the
      duration and intensity of the responses to the first low pH injection did not
      differ between them. Upon repetition, duration and intensity of the pH responses
      increased more than twofold in CMi fibres only. Furthermore, combined application
      of pH and PGE2 sensitized the response in CMi fibres only. In contrast, heat
      activation thresholds were sensitized by the combination of low pH and PGE2 in
      both fibre classes. CONCLUSIONS: Our results confirm nociceptor class independent
      heat sensitization by PGE2 which is probably mediated by transient receptor
      potential vanilloid 1 phosphorylation. However, prolonged and increased pain
      responses in humans upon low pH/PGE2 stimulation appear to be primarily dependent
      on CMi fibres, whereas CM nociceptors appear crucial for phasic responses.

PMID- 24890617
TI  - Microbial heterotrophic production in an oligotrophic acidic geothermal lake:
      responses to organic amendments and terrestrial plant litter.
AB  - Boiling Springs Lake (BSL) is an oligotrophic, acidic geothermal feature where
      even very low levels of microbial heterotrophic production still exceed
      autotrophy. To test whether allochthonous leaf litter (LL) inputs fuel this
      excess, we quantified leaf litterfall, leaching and decomposition kinetics, and
      measured the impact of organic amendments on production, germination and cell
      growth, using pyrosequencing to track changes in microbial community composition.
      Coniferous leaves in BSL exhibited high mass loss rates during leaching and
      decomposition, likely due to a combination of chemical hydrolysis and
      contributions of both introduced and endemic microbes. We measured very low in
      situ (3)H-thymidine incorporation over hours by the dominant chemolithotroph
      Acidimicrobium (13-65 MUg C L(-1) day(-1)), which was inhibited by simple C
      sources (acetate, glucose). Longer term incubations with additions of 0.01-0.02%
      complex C/N sources induced germination of the Firmicute Alicyclobacillus within
      1-2 days, as well as growth of Acetobacteraceae after 3-4 days. LL additions
      yielded the opposite successional patterns of these r-selected heterotrophs,
      boosting production to 30-150 MUg C L(-1) day(-1). Growth and germination studies
      suggest both prokaryotes and fungi likely consume allochthonous organics, and
      might be novel sources of lignocellulose-degrading enzymes. A model of BSL's C
      budget supports the hypothesis that allochthonous inputs fuel seasonal microbial
      heterotrophy, but that dissolved organic C sources greatly exceed direct LL
      inputs.

PMID- 24890618
TI  - Prognostic significance of body mass index before treatment for head and neck
      cancer.
AB  - BACKGROUND: Patients with head and neck cancer frequently experience
      malnutrition. The purpose of this study was to examine the impact of nutritional
      status on prognosis and its association with treatment modalities. METHODS: This
      retrospective study included 706 patients with head and neck cancer diagnosed
      between 2004 and 2012. The effects of pretreatment body mass index (BMI) on
      overall survival were analyzed using the Kaplan-Meier method and Cox regression
      model. RESULTS: BMI ranged from 11.6 to 38.0 kg/m2 (median, 21.5) and was a
      prognostic factor for survival, independent of primary site, and tumor stage. The
      5-year survival rates for underweight, normal, and overweight groups were 32.2%,
      62.7%, and 73.5%, respectively. The hazard ratios of BMI in the surgery,
      chemoradiation, and radiation groups were 0.95, 0.91, and 0.79, respectively, and
      the latter two were statistically significant. CONCLUSION: The impact of BMI is
      determined by the types of cancer treatment. Pretreatment BMI should be
      considered while deciding treatment.

PMID- 24890619
TI  - Narrow band imaging facilitates detection of inlet patches in the cervical
      oesophagus.
AB  - BACKGROUND: Proximal esophageal heterotopic gastric mucosa or so-called inlet
      patch in the cervical oesophagus is easily missed on endoscopic examination
      because of its localisation, usually just below the upper oesophageal sphincter.
      We evaluated the clinical use of narrow band imaging for detection of inlet
      patches. METHODS: In this prospective, controlled observational study, 1407
      subsequent patients underwent oesophagogastroduodenoscopy with or without narrow
      band imaging on withdrawal of the endoscope in the cervical oesophagus. RESULTS:
      One endoscopist who was not aware of the prospective observation documented 6
      (1.17%) cases of inlet patches in 515 oesophagogastroduodenoscopies compared to 4
      cases out of 382 (1.05%) performed by the endoscopist who paid special attention
      to the presence of inlet patches but did not routinely apply narrow band imaging
      (OR 0.89, CI 95% 0.25-3.20, p=0.85). In comparison, 17 cases of inlet patches out
      of 510 (3.33%) were detected by the endoscopist who routinely applied narrow band
      imaging. The detection rate of proximal oesophageal heterotopic gastric mucosa
      using narrow band imaging was significantly higher compared to white light
      endoscopy only (OR 3.06, CI 95% 1.39-6.73, p=0.005). CONCLUSIONS: Withdrawal of
      the endoscope from the cervical oesophagus using narrow band imaging increased
      the detection of inlet patches about three-fold compared to standard white light
      endoscopy.

PMID- 24890620
TI  - Authors' reply to Comment on "No impact of interleukin-28B polymorphisms on
      spontaneous or drug-induced hepatitis delta virus clearance" [Dig. Liver
      Dis.2014;46:348-52].

PMID- 24890621
TI  - Occurrence of inflammatory bowel disease in central Italy: a study based on
      health information systems.
AB  - BACKGROUND: The burden of inflammatory bowel diseases, including Crohn's disease
      and ulcerative colitis, has never been estimated in Italy using administrative
      data sources. Our objective was to measure the occurrence of inflammatory bowel
      diseases in the Lazio region (Italy) using administrative data and to test the
      sensitivity of the Crohn's disease case-finding algorithm with respect to
      clinical diagnosis. METHODS: We conducted a population-based cross-sectional
      study identifying prevalent and incident cases. We estimated occurrence rates of
      inflammatory bowel diseases using hospital discharges or activation of copayment
      exemptions. Sensitivity was calculated from 2358 subjects with clinical diagnosis
      of Crohn's disease. RESULTS: Exemptions identified more than 20% of the cases.
      Prevalence rates (per 100,000) on December 31, 2009 for males and females were
      177 and 144 for ulcerative colitis and 91 and 81 for Crohn's disease,
      respectively. The incidence rates during the years 2008-2009 were 14.5 and 12.2
      for ulcerative colitis and 7.4 and 6.5 for Crohn's disease for males and females,
      respectively. The sensitivity of the administrative sources was 82.2%.
      CONCLUSIONS: Health and population data sources allow the estimation of
      inflammatory bowel diseases occurrence. The age-specific peaks of diagnosis were
      consistent with those reported in other studies. Sensitivity may be affected by
      temporal changes in the quality of the data sources.

PMID- 24890622
TI  - Multifocal peliosis hepatis simulating metastatic malignancy.

PMID- 24890623
TI  - Overall acceptability and efficacy of commonly used bowel preparations for
      colonoscopy in Italian clinical practice. A multicentre prospective study.
AB  - BACKGROUND & AIMS: The recent enormous increase in colonoscopy demand prompted
      this multicentre observational study assessing overall acceptability and efficacy
      of commonly used bowel preparations in Italian clinical practice. METHODS:
      Consecutive outpatients undergoing colonoscopy were recruited from 9 major
      gastroenterological centres in Italy. Each patient evaluated overall
      acceptability of the bowel cleansing preparation through a 0-100mm Visual
      Analogue Scale. The Visual Analogue Scale score was dichotomized by a median
      split: 80-100 (high acceptability) vs. 0-79 (low acceptability). Bowel cleansing
      was assessed through a validated scale. The influence of potential individual
      determinants on patients' acceptability and cleansing efficacy of the bowel
      preparations was determined by multivariate analyses. RESULTS: 599 evaluable
      patients were enrolled; 57.3% received 4L-PEG preparations, 29.5% 2L-PEG
      preparations and 13.2% 2-glasses-solutions (Na-phosphate/Mg-citrate/Na
      picosulphate-containing preparations). Overall acceptability was significantly
      higher for 2L-PEG and 2-glasses solutions than 4L-PEG (adjusted odds ratio, 4.72;
      and adjusted odds ratio 2.07, respectively). Successful bowel cleansing achieved
      with 4L-PEG (85.9%) was similar to 2L-PEG (85.3%; adjusted odds ratio 0.82) and
      significantly higher than 2-glasses solutions (69.6%; adjusted odds ratio 0.34
      vs. 4L-PEG). Split regimen, lower total preparation volume and colonoscopy reason
      (periodical control vs. 1st procedure) were significantly associated with high
      acceptability. Age >=60 years, dissatisfaction with the preparation taken, and
      <=4/week bowel movements were major determinants of a poor bowel cleansing.
      CONCLUSIONS: 2L-PEG and 4L-PEG preparations provide the most effective bowel
      cleansing for colonoscopy in clinical practice, with a significantly higher
      acceptability for 2L-PEG preparations.

PMID- 24890624
TI  - Reduced effects of thyroid hormone on gene expression and metamorphosis in a
      paedomorphic plethodontid salamander.
AB  - It has been over a century since Gudernatsch (1912, Wilhelm Roux Arch Entwickl
      Mech Org 35:457-483) demonstrated that mammalian thyroid gland extracts can
      stimulate tadpole metamorphosis. Despite the tremendous developmental diversity
      of amphibians, mechanisms of metamorphosis have mostly been studied in a few
      model systems. This limits our understanding of the processes that influence the
      evolution of developmental aberrations. Here we isolated thyroid hormone
      receptors alpha (TRalpha) and beta (TRbeta) from Oklahoma salamanders (Eurycea
      tynerensis), which exhibit permanently aquatic (paedomorphic) or biphasic
      (metamorphic) developmental modes in different populations. We found that TRalpha
      and TRbeta were upregulated by thyroid hormone (T3 ) in tail tissues of larvae
      from metamorphic populations, but basal levels of TR expression and T3
      responsiveness were reduced in larvae from paedomorphic populations. Likewise, we
      found that T3 treatment resulted in complete loss of larval epibranchials in
      larvae from metamorphic populations, but little to no epibranchial remodeling
      occurred in larvae from paedomorphic populations over the same duration. This is
      the first study to directly demonstrate reduced gene expression and metamorphic
      responses to T3 in a paedomorphic plethodontid compared to metamorphic
      conspecifics, and the first salamander system to show differential expression of
      thyroid hormone receptors associated with alternative developmental patterns.

PMID- 24890625
TI  - Fatal falls in the U.S. residential construction industry.
AB  - BACKGROUND: Falls from heights remain the most common cause of workplace
      fatalities among residential construction workers in the United States. METHODS:
      This paper examines patterns and trends of fall fatalities in U.S. residential
      construction between 2003 and 2010 by analyzing two large national datasets.
      RESULTS: Almost half of the fatalities in residential construction were from
      falls. In the residential roofing industry, 80% of fatalities were from falls. In
      addition, about one-third of fatal falls in residential construction were among
      self-employed workers. Workers who were older than 55 years, were Hispanic
      foreign-born, or employed in small establishments (1-10 employees) also had
      higher proportions of fatal falls in residential construction compared to those
      in nonresidential construction. CONCLUSIONS: The findings suggest that fall
      safety within the residential construction industry lags behind commercial
      construction and industrial settings. Fall prevention in residential construction
      should be enhanced to better protect construction workers in this sector.

PMID- 24890626
TI  - Improving bone repair of femoral and radial defects in rabbit by incorporating
      PRP into PLGA/CPC composite scaffold with unidirectional pore structure.
AB  - In this study, a platelet-rich plasma poly(lactic-co-glycolic acid) (PRP
      PLGA)/calcium phosphate cement (CPC) composite scaffold was prepared by
      incorporating PRP into PLGA/CPC scaffold with unidirectional pore structure,
      which was fabricated by the unidirectional freeze casting of CPC slurry and the
      following infiltration of PLGA. The results from in vitro cell experiments and in
      vivo implantation in femoral defects manifested that incorporation of PRP into
      PLGA/CPC scaffold improved in vitro cell response (cell attachment,
      proliferation, and differentiation), and markedly boosted bone formation,
      angiogenesis and material degradation. The incorporation of PRP into scaffold
      showed more outstanding improvement in osteogenesis as the scaffolds were used to
      repair the segmental radial defects, especially at the early stage. The new bone
      tissues grew along the unidirectional lamellar pores of scaffold. At 12 weeks
      postimplantation, the segmental radial defects treated with PRP-PLGA/CPC scaffold
      had almost recuperated, whereas treated with the scaffold without PRP was far
      from healed. Taken together, the PRP-PLGA/CPC scaffold with unidirectional pore
      structure is a promising candidate to repair bone defects at various sites.

PMID- 24890627
TI  - Inhibitory effects of carvone isomers on the GABAA receptor in primary cultures
      of rat cortical neurons.
AB  - Carvone is a natural terpene which can be purified as R-(-) or S-(+) enantiomers.
      There are many reports about its antibacterial, antifungal, and insecticide
      activities, and also of some effects on the nervous system, where both
      enantiomers showed different potencies. Considering that the GABA(A) receptor is
      a major insecticide target, we studied the pharmacological activity of both
      carvone enantiomers, and of thujone as a reference compound acting on the
      receptor, on native GABA(A) by determining their effects on benzodiazepine
      recognition sites using primary neuronal cultures. Both isomers were able to
      inhibit the GABA-induced stimulation of [(3)H]flunitrazepam binding, suggesting
      their interaction with the GABA(A) receptor as negative allosteric modulators.
      Their activity was comparable to that described for thujone in the present
      article, with the R-(-)-carvone being the more similar and potent stereoisomer.
      The different configuration of the isopropenyl group in position 5 thus seems to
      be significant for receptor interaction and the bicycle structure not to be
      critical for receptor recognition. The concentrations necessary to induce
      negative modulation of the receptor were not cytotoxic in a murine neuron culture
      system. These results confirm that, at least partially, the reported insecticidal
      activity of carvones may be explained by their interaction with the GABA(A)
      receptor at its noncompetitive blocker site.

PMID- 24890628
TI  - Pediatric mycosis fungoides in Singapore: a series of 46 children.
AB  - Few studies have evaluated Asian children with mycosis fungoides (MF). We report
      a series of patients from a tertiary dermatologic institution in Singapore. A
      retrospective review was performed of patients younger than 16 years old
      diagnosed with MF between 2000 and 2008 at the National Skin Centre, Singapore.
      Forty-six patients were identified. At initial presentation, a provisional
      diagnosis of MF was made in 19 patients (41.3%), pityriasis lichenoides chronica
      (PLC) in 11 (23.9%) and postinflammatory hypopigmentation due to eczema or other
      causes in 11 (23.9%). After skin biopsy, the hypopigmented variant of MF was
      diagnosed in 42 patients (91.3%). There was one case each of PLC-like MF,
      pigmented purpuric dermatosis-like MF, classic MF, and solitary MF. Pityriasis
      lichenoides coexisted in three cases (6.5%). All except one patient presented
      with the early patch-plaque stage of disease (stage IA/B). The disease did not
      progress in any of our patients after a mean follow-up of 71.0 +/- 52.5 months.
      Twenty-seven patients (58.7%) had complete disease clearance after a mean
      duration of 27.1 +/- 28.1 months; 15 (49.7%) of 32 patients who received
      narrowband ultraviolet B treatment had complete clearance within an average of
      8.9 +/- 5.3 months, but 7 patients relapsed within 14.9 +/- 14.8 months. One
      patient with solitary MF failed multiple treatment modalities before eventually
      achieving disease clearance with photodynamic therapy. Hypopigmented MF is the
      most common MF variant in Asian children. The diagnostic difficulty is in
      differentiating this from PLC, which may coexist with MF. Long-term prognosis is
      generally favorable. 

PMID- 24890629
TI  - Two cases of bilateral earlobe cutaneous pseudolymphoma.

PMID- 24890630
TI  - The effect of altitude on inhaler performance.
AB  - The purpose of the study is to understand the effect of altitude on the
      performance of selected pressurized metered dose inhalers (pMDIs) and dry powder
      inhalers (DPIs). A testing apparatus that created consistent breath profiles
      through the Alberta Idealized Throat was designed to test five pMDIs and two DPIs
      at altitudes of 670, 2450, 3260, and 4300 m. Both gravimetric and chemical assays
      were conducted to determine the in vitro lung dose. Additionally, spray duration
      and shot weight for pMDIs and device resistance for DPI were measured. There was
      no significant change in in vitro lung dose for any of the pMDIs tested. Shot
      weight and spray duration were unaffected. The device resistance of the DPIs
      decreased with increasing altitude and was successfully modeled as a function of
      ambient pressure. The in vitro lung dose of both DPIs showed no significant
      change when operated with an inhaler pressure drop of 4 kPa, but for the
      Bricanyl((r)) Turbuhaler((r)), a significant decrease occurred when matching the
      volumetric inspiratory flow rate to that of the baseline altitude.

PMID- 24890633
TI  - Salvage therapy for recurrence of bladder cancer: do we need a uniform approach?
AB  - The activity of chemotherapy as salvage therapy for recurrent bladder cancer has
      been well defined, although the optimum therapy combination is less clear. Since
      the early nineties several cisplatin based regimens have been compared but no one
      regimen has reported a superior benefit. Currently, regimens such as
      methotrexate, vinblastine, doxorubicin and cisplatin and gemcitabine-cisplatin
      should be considered two equal alternatives in patients eligible for cisplatin,
      but the differing toxicity profiles should be evaluated in the choice of
      treatment. The use of a triple combination with paclitaxel, gemcitabine and
      cisplatin should be avoided in clinical practice, although its use may be
      carefully considered in patients needing a rapid downsizing of disease and with
      primary bladder tumor. Despite this evidence, several questions remain, and there
      is a need for answers in the future.

PMID- 24890634
TI  - [Heart transplantation in France: Current status].
AB  - The ratio of candidates per transplant is 2.1. Forty-eight percent of candidates
      have been transplanted within 12months of listing. Twenty-five French centers
      performed 397 heart transplants in 2012 (6.1 pmp). Forty-eight percent of
      patients receiving a transplant have an urgency status. One-year survival is 76%.
      The annual attrition rate is 2-3% in patients surviving the first year. Risk
      factors for 1-year mortality are donor specific, center specific and recipient
      specific. Patient-based graft allocation policy requires a reliable measure of
      mortality risk in candidates as well as of transplant benefit. 

PMID- 24890635
TI  - [Difficulties to access to liver transplantation in France in 2014].

PMID- 24890631
TI  - The underlying chemistry of electronegative LDL's atherogenicity.
AB  - Electronegative low-density lipoprotein (LDL) found in human plasma is highly
      atherogenic, and its level is elevated in individuals with increased
      cardiovascular risk. In this review, we summarize the available data regarding
      the elevation of the levels of electronegative LDL in the plasma of patients with
      various diseases. In addition, we discuss the harmful effects and underlying
      mechanisms of electronegative LDL in various cell types. We also highlight the
      known biochemical properties of electronegative LDL that may contribute to its
      atherogenic functions, including its lipid and protein composition, enzymatic
      activities, and structural features. Given the increasing recognition of
      electronegative LDL as a potential biomarker and therapeutic target for the
      prevention of cardiovascular disease, key future goals include the development of
      a standard method for the detection of electronegative LDL that can be used in a
      large-scale population survey and the identification and testing of strategies
      for eliminating electronegative LDL from the blood. 

PMID- 24890636
TI  - [Lower limb occlusive arterial disease: Diagnosis problems in 2014].
AB  - Diagnosis of peripheral occlusive arterial disease still raises many problems in
      2014. Early detection is crucial and a very good tool is available: ankle
      brachial index. In some patients, toe systolic pressure measurement might be
      useful (patients with diabetes mellitus or renal failure). As far as walking
      symptoms are concerned, treadmill test usually gives the answer about the reason
      for pain. In some cases, other tests may be useful, i.e. treadmill TcPO2 in low
      back pain. Critical ischaemia is a major issue for treatment when
      revascularization has failed but diagnosis also raises concerns. Objective
      testing for ischaemia is mandatory (TcPO2, toe systolic pressure). Ankle pressure
      measurement is not sufficient in those patients. Patients suspected for critical
      limb ischaemia have to be investigated and treated in vascular centers. Many
      problems still concern diagnosis of peripheral occlusive arterial disease in
      2014. 

PMID- 24890632
TI  - HDL: to treat or not to treat?
AB  - Several studies have shown an inverse relationship between HDL cholesterol (HDL
      C) levels and the risk of cardiovascular disease. Low HDL-C levels are commonly
      present in subjects with diabetes, metabolic syndrome, or obesity. These
      observations have suggested that increasing HDL concentrations might help in
      decreasing the cardiovascular disease risk. However, despite initial positive
      results, some recent data from clinical trials with HDL-raising therapies failed
      to confirm this hypothesis; in addition, data from Mendelian randomization
      analyses showed that nucleotide polymorphisms associated with increased HDL-C
      levels did not decrease the risk of myocardial infarction, further challenging
      the concept that higher HDL-C levels will automatically translate into lower
      cardiovascular disease risk. Differences in the quality and distribution of HDL
      particles might partly explain these findings, and in agreement with this
      hypothesis, some observations have suggested that HDL subpopulation levels may be
      better predictors of cardiovascular disease than simple HDL-C levels. Thus, it is
      expected that increased HDL-C levels may be beneficial when associated with an
      improvement in HDL function, suggesting that pharmacological approaches able to
      correct or increase HDL functions might produce more reliable clinical benefits. 

PMID- 24890637
TI  - [The MitraClip procedure].
AB  - Mitral insufficiency is a frequently occurring valvular disease for which surgery
      is the reference treatment. A large number of patients are at high risk or even
      contraindicated for surgery due to comorbidities. The MitraClip procedure
      reproduces a surgical technique for mitral valve repair. Global experience
      includes over 12,000 patients and has been mainly reported in registries with
      limited follow-up. The degree of reduction of mitral insufficiency is less with
      the MitraClip than with surgery. Safety of the procedure is good in experienced
      centres. Most patients have functional improvement in the mid-term. The procedure
      may be considered in patients who are at high risk for surgery and remain
      symptomatic despite optimal medical treatment. In the future, more data are
      needed from longer follow-up and randomised trials. Both the technique and the
      equipment used in the procedure need to improve. In addition, it is hoped that
      combined percutaneous procedures will be available in the near future. 

PMID- 24890638
TI  - [Sport's related sudden death].
AB  - Non-traumatic sudden death related to sport is a rare but always dramatic event.
      Its causes are mainly cardiovascular. Prevention of sudden death depends on
      effective medical examination involving history, physical examination and resting
      ECG, as education of athletes who must follow the rules for safe sport practice
      and lastly training for emergency actions of the population. 

PMID- 24890639
TI  - [Electronic cigarette: Reliable and efficient?].
AB  - Before 2010, the e-cigarette remains inefficient then, its dissemination explodes
      in 2013 where more than 10 million people have tried it in France. The best made
      e-cigarette will always be potentially toxic and an addictive product. The e
      cigarette is not a suitable product for non-smokers and could participate to
      normalize tobacco in society. To end tobacco, e-cigarette must provide a pleasant
      throat hit to the smoker in the first 6 seconds then deliver an adequate dose of
      nicotine. The majority of smokers who have tried the e-cigarette do not adopt the
      product because they did not like it. Health professional must help those who
      smoke and use e-cigarettes to remove the last cigarettes.

PMID- 24890640
TI  - [Epidemiology, prognostic data of cardiac arrest in 2014].
AB  - Epidemiological data on the incidence, the survival and the prognostic factors of
      cardiac arrest (CA) are often heterogeneous. However, recent advances in
      methodology and research have improved the knowledge on that topic. The prognosis
      of victims CA depends on the initial patient's characteristics, the circumstances
      of the CA and the quality of the management. As a result, the subsequent outcome
      of these patients relies on the efficiency of the chain of survival: prompt
      alert, bystander cardiopulmonary resuscitation and early defibrillation, the
      advanced care life support provided by the emergency medical services and the
      integration of in-hospital care. Other parameters are also likely to influence
      the prognosis (such as the system of care or the environment) though their
      assessment remains incomplete. More important, factors potentially affecting the
      long-term outcome are currently very less investigated. Finally, despite the
      potential improvements in the management of these patients for some years now,
      the temporal trends of the overall survival appear fairly stable. The transition
      in the profile of patients could partly explain the absence of clear effect on
      survival. 

PMID- 24890641
TI  - Management of positive sub-areolar/nipple duct margins in nipple-sparing
      mastectomies.
AB  - We evaluated management of positive sub-areolar/nipple duct margins in nipple
      sparing mastectomies (NSM) at our institution. Retrospective chart review of all
      NSM from January 2007 to April 2012 was performed and patient, tumor, and
      treatment information was collected. Sub-areolar/nipple duct margins included
      ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub
      areolar/nipple duct margins; 21 of 220 cancer-bearing breasts (10%) and 1 of 218
      prophylactic mastectomies (0.5%). Positive margins included four with invasive
      lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management
      included removal of eight nipples and nine nipple areola complexes (NAC). Four of
      17 nipple/NAC specimens had evidence of residual DCIS and none had residual
      invasive cancer. The majority of nipple/NAC specimens excised for a positive
      margin had no residual malignancy. Future studies are needed to determine the
      extent of NAC tissue removal required for positive margins. 

PMID- 24890642
TI  - Susceptibility of Culicoides species biting midges to deltamethrin-treated nets
      as determined under laboratory and field conditions in the Balearic Islands,
      Spain.
AB  - Culicoides Latreille (Diptera: Ceratopogonidae) are vectors of several
      arboviruses, including bluetongue virus (BTV) and African horse sickness virus
      (AHSV), which cause diseases in, respectively, sheep and cattle, and horses, and
      have economic repercussions mainly as a result of trade restrictions.
      Insecticides can be used to reduce vector populations and hence the spread of
      disease. Despite the economic importance of these diseases, relatively few
      studies have evaluated the efficacy of commercially available insecticides and
      the effectiveness of treated nets against Culicoides species. The aim of the
      present study was to evaluate the insecticidal effect of commercially available
      polyethylene nets (ZeroVector((r)) ) treated with deltamethrin (4.4 g/kg +/- 15%)
      on Culicoides species. Laboratory and field trials were conducted in Culicoides
      populations collected in Majorca in the Balearic Islands, Spain. The present
      study shows that deltamethrin-treated nets provoke high and rapid mortality (90
      100%) in Culicoides midges under laboratory conditions and increase mortality by
      13% when deployed in the field. 

PMID- 24890643
TI  - An efficient siRNA-mediated gene silencing in primary human monocytes, dendritic
      cells and macrophages.
AB  - Mononuclear phagocytes (MP) comprise monocytes, macrophages (MPhi) and dendritic
      cells (DC), including their lineage-committed progenitors, which together have an
      eminent role in health and disease. Lipid-based siRNA-mediated gene inactivation
      is an established approach to investigate gene function in MP cells. However,
      although there are few protocols dedicated for siRNA-mediated gene inactivation
      in primary human DC and MPhi, there are none available for primary human
      monocytes. Moreover, there is no available method to perform comparative studies
      of a siRNA-mediated gene silencing in primary monocytes and other MP cells. Here,
      we describe a protocol optimized for the lipid-based delivery of siRNA to perform
      gene silencing in primary human blood monocytes, which is applicable to DCs, and
      differs from the classical route of siRNA delivery into MPhis. Along with this
      protocol, we provide a comparative analysis of how monocytes, DC and MPhi are
      efficiently transfected with the target siRNA without affecting cell viability,
      resulting in strong gene knockdown efficiency, including the simultaneous
      inactivation of two genes. Moreover, siRNA delivery does not affect classical
      functions in MP such as differentiation, phagocytosis and migration,
      demonstrating that this protocol does not induce non-specific major alterations
      in these cells. As a proof-of-principle, a functional analysis of hematopoietic
      cell kinase (Hck) shows for the first time that this kinase regulates the
      protease-dependent migration mode in human monocytes. Collectively, this protocol
      enables efficient gene inactivation in primary MP, suggesting a wide spectrum of
      applications such as siRNA-based high-throughput screening, which could
      ultimately improve our knowledge about MP biology. 

PMID- 24890644
TI  - A hierarchical Bayesian model averaging framework for groundwater prediction
      under uncertainty.
AB  - Groundwater prediction models are subjected to various sources of uncertainty.
      This study introduces a hierarchical Bayesian model averaging (HBMA) method to
      segregate and prioritize sources of uncertainty in a hierarchical structure and
      conduct BMA for concentration prediction. A BMA tree of models is developed to
      understand the impact of individual sources of uncertainty and uncertainty
      propagation to model predictions. HBMA evaluates the relative importance of
      different modeling propositions at each level in the BMA tree of model weights.
      The HBMA method is applied to chloride concentration prediction for the "1,500
      foot" sand of the Baton Rouge area, Louisiana from 2005 to 2029. The groundwater
      head data from 1990 to 2004 is used for model calibration. Four sources of
      uncertainty are considered and resulted in 180 flow and transport models for
      concentration prediction. The results show that prediction variances of
      concentration from uncertain model elements are much higher than the prediction
      variance from uncertain model parameters. The HBMA method is able to quantify the
      contributions of individual sources of uncertainty to the total uncertainty. 

PMID- 24890645
TI  - Multiple sclerosis: Does aggressive MS warrant aggressive treatment?

PMID- 24890648
TI  - Clinico-histopathologic and outcome features of cutaneous infundibular
      keratinizing acanthoma: a case report and literature review.
AB  - The infundibular keratinizing acanthoma (IKA) is a rare epithelial benign keratin
      containing neoplasm of hair follicles. The purpose of this study was to evaluate
      the defining histopathologic architecture of IKA. A typical IKA consisted of a
      keratin-filled crypt in the dermis and subcutis that opened to the skin surface.
      Most of this tumor occurred on the back, neck, head, and the shoulders.
      Microscopically, the dermal nodules were focally contiguous in both the dermis
      and subcutis. Furthermore, most histological lesions are consistent with a simple
      or multiloculated cyst filled with keratin and lined by a wall of stratified
      squamous epithelium; keratin appears as a concentric lamellar mass, with a
      keratotic pearly aspect. Histological examination of the cutaneous lesions
      revealed that the growths were comprised of IKA. IKA of man and dog were
      compared, and it was concluded that although they are similar in many respects,
      they are not identical entities. To the best of our knowledge, this is the first
      report on the prevalence of IKAs among the population of owned dogs in Iran. 

PMID- 24890649
TI  - Simultaneous determination of seven phthalic acid esters in beverages using
      ultrasound and vortex-assisted dispersive liquid-liquid microextraction followed
      by high-performance liquid chromatography.
AB  - A sensitive, rapid, and simple high-performance liquid chromatography with UV
      detection method was developed for the simultaneous determination of seven
      phthalic acid esters (dimethyl phthalate, dipropyl phthalate, di-n-butyl
      phthalate, benzyl butyl phthalate, dicyclohexyl phthalate, di-(2-ethylhexyl)
      phthalate, and di-n-octyl phthalate) in several kinds of beverage samples.
      Ultrasound and vortex-assisted dispersive liquid-liquid microextraction method
      was used. The separation was performed using an Intersil ODS-3 column (C18 , 250
      * 4.6 mm, 5.0 MUm) and a gradient elution with a mobile phase consisting of
      MeOH/ACN (50:50) and 0.2 M KH2 PO4 buffer. Analytes were detected by a UV
      detector at 230 nm. The developed method was validated in terms of linearity,
      limit of detection, limit of quantification, repeatability, accuracy, and
      recovery. Calibration equations and correlation coefficients (> 0.99) were
      calculated by least squares method with weighting factor. The limit of detection
      and quantification were in the range of 0.019-0.208 and 0.072-0.483 MUg/L. The
      repeatability and intermediate precision were determined in terms of relative
      standard deviation to be within 0.03-3.93 and 0.02-4.74%, respectively. The
      accuracy was found to be in the range of -14.55 to 15.57% in terms of relative
      error. Seventeen different beverage samples in plastic bottles were successfully
      analyzed, and ten of them were found to be contaminated by different phthalic
      acid esters. 

PMID- 24890646
TI  - Cataplexy--clinical aspects, pathophysiology and management strategy.
AB  - Cataplexy is the pathognomonic symptom of narcolepsy, and is the sudden
      uncontrollable onset of skeletal muscle paralysis or weakness during wakefulness.
      Cataplexy is incapacitating because it leaves the individual awake but
      temporarily either fully or partially paralyzed. Occurring spontaneously,
      cataplexy is typically triggered by strong positive emotions such as laughter and
      is often underdiagnosed owing to a variable disease course in terms of age of
      onset, presenting symptoms, triggers, frequency and intensity of attacks. This
      disorder occurs almost exclusively in patients with depletion of hypothalamic
      orexin neurons. One pathogenetic mechanism that has been hypothesized for
      cataplexy is the activation, during wakefulness, of brainstem circuitry that
      normally induces muscle tone suppression in rapid eye movement sleep. Muscle
      weakness during cataplexy is caused by decreased excitation of noradrenergic
      neurons and increased inhibition of skeletal motor neurons by gamma-aminobutyric
      acid-releasing or glycinergic neurons. The amygdala and medial prefrontal cortex
      contain neural pathways through which positive emotions probably trigger
      cataplectic attacks. Despite major advances in understanding disease mechanisms
      in cataplexy, therapeutic management is largely symptomatic, with antidepressants
      and gamma-hydroxybutyrate being the most effective treatments. This Review
      describes the clinical and pathophysiological aspects of cataplexy, and outlines
      optimal therapeutic management strategies.

PMID- 24890651
TI  - Influence of the number and severity of somatic symptoms on the severity of
      depression and suicidality in community-dwelling elders.
AB  - INTRODUCTION: Older adults commonly experience somatic symptoms, and those who do
      are more likely to have depressive disorders as well. Our goal in this study is
      to examine the influence of the number and severity of somatic symptoms on the
      severity of depressive symptoms, including suicidality, in elderly adults.
      METHODS: This study was conducted as part of the Ansan Geriatric (AGE) Study, a
      community-based cohort study in Ansan City, South Korea. A total of 3,210 elderly
      adults aged 60 years or over (1,388 males and 1,770 females) participated in this
      study. The Korean version of the Beck Depression Inventory (BDI) was used to
      measure depressive symptoms and suicidality. Somatic symptoms were assessed by
      the Patient Health Questionnaire-15 (PHQ-15). RESULTS: Both mild and severe
      somatic symptoms significantly increased the risk for severe depression and high
      suicidality. Severe somatic symptoms doubled the risk for severe depression and
      suicidal intent. DISCUSSION: Somatic symptoms not fully explained as medical
      illnesses are closely associated with late-life depression, even after
      adjustments for comorbid physical illnesses and other confounding factors. The
      presence of somatic symptoms concurrent with, but not fully explained by comorbid
      physical illness or disability, seems to be an independent marker for predicting
      the severity of late-life depression and suicidality.

PMID- 24890653
TI  - Catechol-rhodanine derivatives: Specific and promiscuous inhibitors of
      Escherichia coli deoxyxylulose phosphate reductoisomerase (DXR).
AB  - To develop more effective inhibitors than fosmidomycin, a natural compound which
      inhibits the deoxyxylulose 5-phosphate reductoisomerase (DXR), the second enzyme
      of the MEP pathway, we designed molecules possessing on the one hand a catechol
      that is able to chelate the magnesium dication and on the other hand a group able
      to occupy the NADPH recognition site. Catechol-rhodanine derivatives (1-6) were
      synthesized and their potential inhibition was tested on the DXR of Escherichia
      coli. For the inhibitors 1 and 2, the presence of detergent in the enzymatic
      assays led to a dramatic decrease of the inhibition suggesting, that these
      compounds are rather promiscuous inhibitors. The compounds 4 and 5 kept their
      inhibition capacity in the presence of Triton X100 and could be considered as
      specific inhibitors of DXR. Compound 4 showed antimicrobial activity against
      Escherichia coli. The only partial protection of NADPH against the inhibition
      suggested that the catechol-rhodanine derivatives did not settle in the coenzyme
      binding site. This paper points out the necessity to include a detergent in the
      DXR enzymatic assays to avoid false positive when putative hydrophobic inhibitors
      are tested and especially when the IC50, are in the micromolar range. 

PMID- 24890654
TI  - Enzymatic preparation of cis and trans-3-amino-4-hydroxytetrahydrofurans and cis
      3-amino-4-hydroxypyrrolidines.
AB  - The lipase catalyzed resolution of cis and trans-3-amino-4
      hydroxytetrahydrofurans and cis-3-amino-4-hydroxypyrrolidines have been studied.
      For all the heterocycles, the best enantioselectivity was obtained using Candida
      antarctica lipases A and B as catalysts in hydrolytic processes. The absolute
      configuration of the optically pure obtained heterocycles has been assigned. 

PMID- 24890652
TI  - The design and discovery of water soluble 4-substituted-2,6-dimethylfuro[2,3
      d]pyrimidines as multitargeted receptor tyrosine kinase inhibitors and
      microtubule targeting antitumor agents.
AB  - The design, synthesis and biological evaluations of fourteen 4-substituted 2,6
      dimethylfuro[2,3-d]pyrimidines are reported. Four compounds (11-13, 15) inhibit
      vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth
      factor receptor beta (PDGFR-beta), and target tubulin leading to cytotoxicity.
      Compound 11 has nanomolar potency, comparable to sunitinib and semaxinib, against
      tumor cell lines overexpressing VEGFR-2 and PDGFR-beta. Further, 11 binds at the
      colchicine site on tubulin, depolymerizes cellular microtubules and inhibits
      purified tubulin assembly and overcomes both betaIII-tubulin and P-glycoprotein
      mediated drug resistance, and initiates mitotic arrest leading to apoptosis. In
      vivo, its HCl salt, 21, reduced tumor size and vascularity in xenograft and
      allograft murine models and was superior to docetaxel and sunitinib, without
      overt toxicity. Thus 21 affords potential combination chemotherapy in a single
      agent. 

PMID- 24890655
TI  - Sulfur, selenium and tellurium pseudopeptides: synthesis and biological
      evaluation.
AB  - A new series of sulfur, selenium and tellurium peptidomimetic compounds was
      prepared employing the Passerini and Ugi isocyanide based multicomponent
      reactions (IMCRs). These reactions were clearly superior to conventional methods
      traditionally used for organoselenium and organotellurium synthesis, such as
      classical nucleophilic substitution and coupling methods. From the biological
      point of view, these compounds are of considerable interest because of suspected
      anticancer and antimicrobial activities. While the sulfur and selenium containing
      compounds generally did not show either anticancer or antimicrobial activities,
      their tellurium based counterparts frequently exhibited antimicrobial activity
      and were also cytotoxic. Some of the compounds synthesized even showed selective
      activity against certain cancer cells in cell culture. These compounds induced a
      cell cycle delay in the G0/G1 phase. At closer inspection, the ER and the actin
      cytoskeleton appeared to be the primary cellular targets of these tellurium
      compounds, in line with some of our previous studies. As most of these
      peptidomimetic compounds also comply with Lipinski's Rule of Five, they promise
      good bioavailability, which needs to be studied as part of future investigations.

PMID- 24890656
TI  - Intramolecular C(sp(3))H amination of arylsulfonyl azides with engineered and
      artificial myoglobin-based catalysts.
AB  - The direct conversion of aliphatic CH bonds into CN bonds provides an attractive
      approach to the introduction of nitrogen-containing functionalities in organic
      molecules. Following the recent discovery that cytochrome P450 enzymes can
      catalyze the cyclization of arylsulfonyl azide compounds via an intramolecular
      C(sp(3))H amination reaction, we have explored here the CH amination reactivity
      of other hemoproteins. Various heme-containing proteins, and in particular
      myoglobin and horseradish peroxidase, were found to be capable of catalyzing this
      transformation. Based on this finding, a series of engineered and artificial
      myoglobin variants containing active site mutations and non-native Mn- and Co
      protoporphyrin IX cofactors, respectively, were prepared to investigate the
      effect of these structural changes on the catalytic activity and selectivity of
      these catalysts. Our studies showed that metallo-substituted myoglobins
      constitute viable CH amination catalysts, revealing a distinctive reactivity
      trend as compared to synthetic metalloporphyrin counterparts. On the other hand,
      amino acid substitutions at the level of the heme pocket were found to be
      beneficial toward improving the stereo- and enantioselectivity of these Mb
      catalyzed reactions. Mechanistic studies involving kinetic isotope effect
      experiments indicate that CH bond cleavage is implicated in the rate-limiting
      step of myoglobin-catalyzed amination of arylsulfonyl azides. Altogether, these
      studies indicate that myoglobin constitutes a promising scaffold for the design
      and development of CH amination catalysts. 

PMID- 24890657
TI  - Vgamma9Vdelta2 TCR-activation by phosphorylated antigens requires butyrophilin 3
      A1 (BTN3A1) and additional genes on human chromosome 6.
AB  - Pyrophosphorylated metabolites of isoprenoid-biosynthesis (phosphoantigens, PAgs)
      activate Vgamma9Vdelta2 T cells during infections and trigger antitumor activity.
      This activation depends on expression of butyrophilin 3 A1 (BTN3A1) by antigen
      presenting cells. This report defines the minimal genetic requirements for
      activation of Vgamma9Vdelta2 T cells by PAgs and mAb 20.1. We compared PAg
      presentation by BTN3A1-transduced CHO hamster cells with that of CHO cells
      containing the complete human chromosome 6 (Chr6). BTN3A1 expression alone was
      sufficient for activation of Vgamma9Vdelta2 T-cell receptor transductants by mAb
      20.1., while activation by PAgs also required the presence of Chr6. We take this
      finding as evidence that gene(s) on Chr6 in addition to BTN3A1 are mandatory for
      PAg-mediated activation of Vgamma9Vdelta2 T cells. This observation is important
      for the design of animal models for PAg-mediated immune responses and provokes
      speculations about the analogy between genes controlling PAg presentation and MHC
      localized genes controlling peptide-antigen presentation. 

PMID- 24890660
TI  - 1,4-Cyclohexadienes--easy access to a versatile building block via transition
      metal-catalysed Diels-Alder reactions.
AB  - 1,4-Cyclohexadiene derivatives are easily accessed via transition-metal
      cycloadditions of 1,3-dienes with alkynes. The mild reaction conditions of
      several transition-metal-catalysed reactions allows the incorporation of various
      functional groups to access functionalised 1,4-cyclohexadienes. The control of
      the regiochemistry in the intermolecular cobalt-catalysed Diels-Alder reaction is
      realised utilising different ligand designs. The functionalised 1,4
      cyclohexadiene derivatives are valuable building blocks in follow-up
      transformations. Finally, the oxidation of the 1,4-cyclohexadienes can be
      accomplished under mild conditions to generate the corresponding arene
      derivatives. 

PMID- 24890658
TI  - Copper-catalyzed [18F]fluorination of (mesityl)(aryl)iodonium salts.
AB  - A practical, rapid, and highly regioselective Cu-catalyzed radiofluorination of
      (mesityl)(aryl)iodonium salts is described. This protocol utilizes [(18)F]KF to
      access (18)F-labeled electron-rich, -neutral, and -deficient aryl fluorides under
      a single set of mild conditions. This methodology is applied to the synthesis of
      protected versions of two important radiotracers: 4-[(18)F]fluorophenylalanine
      and 6-[(18)F]fluoroDOPA. 

PMID- 24890659
TI  - Symptom burden among young adults with breast or colorectal cancer.
AB  - BACKGROUND: Cancer incidence has increased among young adults (YAs) and survival
      rates have not improved compared with other age groups. Patient-reported outcomes
      may enhance our understanding of this vulnerable population. METHODS: In a
      multisite prospective study, patients completed a cancer symptom inventory at the
      time of enrollment (T1) and 4 weeks to 5 weeks later (T2). YAs (those aged <= 39
      years) with breast or colorectal cancer were compared with older adults (those
      aged >= 40 years) with breast or colorectal cancer with regard to symptom
      severity, symptom interference, changes over time, and medical care. RESULTS:
      Participants included 1544 patients with breast cancer (96 of whom were YAs) and
      718 patients with colorectal cancer (37 of whom were YAs). Compared with older
      adults, YAs with breast cancer were more likely to report moderate/severe
      drowsiness, hair loss, and symptom interference with relationships at T1. YAs
      with colorectal cancer were more likely to report moderate/severe pain, fatigue,
      nausea, distress, drowsiness, shortness of breath, and rash plus interference in
      general activity, mood, work, relationships, and life enjoyment compared with
      older adults. Compared with older adults, shortness of breath, appetite, and sore
      mouth were more likely to improve in YAs with breast cancer; vomiting was less
      likely to improve in YAs with colorectal cancer. Referrals for supportive care
      were few, especially among patients with colorectal cancer. YAs with breast
      cancer were somewhat more likely to be referred to nutrition and psychiatry
      services than older patients. CONCLUSIONS: YAs reported symptom severity, symptom
      interference, and variations over time that were distinct from older patients.
      Distinctions were found to differ by diagnostic group. These findings enhance the
      understanding of symptom burden in YAs and inform the development of targeted
      interventions and future research.

PMID- 24890661
TI  - Kinetics of tracheid development explain conifer tree-ring structure.
AB  - Conifer tree rings are generally composed of large, thin-walled cells of light
      earlywood followed by narrow, thick-walled cells of dense latewood. Yet, how wood
      formation processes and the associated kinetics create this typical pattern
      remains poorly understood. We monitored tree-ring formation weekly over 3 yr in
      45 trees of three conifer species in France. Data were used to model cell
      development kinetics, and to attribute the relative importance of the duration
      and rate of cell enlargement and cell wall deposition on tree-ring structure.
      Cell enlargement duration contributed to 75% of changes in cell diameter along
      the tree rings. Remarkably, the amount of wall material per cell was quite
      constant along the rings. Consequently, and in contrast with widespread belief,
      changes in cell wall thickness were not principally attributed to the duration
      and rate of wall deposition (33%), but rather to the changes in cell size (67%).
      Cell enlargement duration, as the main driver of cell size and wall thickness,
      contributed to 56% of wood density variation along the rings. This mechanistic
      framework now forms the basis for unraveling how environmental stresses trigger
      deviations (e.g. false rings) from the normal tree-ring structure. 

PMID- 24890662
TI  - The nature and extent of child protection involvement among heroin-using mothers
      in treatment: high rates of reports, removals at birth and children in care.
AB  - INTRODUCTION AND AIMS: A substantial proportion of women in treatment for
      substance use problems are mothers of dependent children, but only a small number
      of studies have explored the nature and extent of their child protection
      involvement with substance-using mothers themselves. DESIGN AND METHODS: A large
      sample of mothers on the opioid treatment program (OTP) in Sydney, Australia,
      were interviewed. This paper describes their characteristics, the extent and
      nature of their involvement with the child protection system, the parenting
      related interventions provided and their views of their own parenting. RESULTS:
      The 171 mothers were disadvantaged and marginalised and had 302 children under
      the age of 16 years, 99 of whom were in out-of-home care. Nearly half the
      children in care (n = 42) had been removed at the time of their birth, and half
      (n = 49) had been removed from a mother who was on an OTP at the time. Among the
      younger children (age 1-2 years), higher proportions had been removed at birth
      than among the older children. None of the 32 mothers who had a child removed at
      birth and then gave birth subsequently retained care of their new baby. Women
      often chose to enter treatment (63.6%) for child-related reasons (35%) and
      attempted to shield their children from their substance use. Few health services
      were provided to them outside the availability of OTP. DISCUSSION AND
      CONCLUSIONS: Entering treatment presents an opportunity for improving outcomes
      for these women and their children and to reduce future involvement with the
      child protection system.

PMID- 24890663
TI  - Construction of a yeast-based signaling biosensor for human angiotensin II type 1
      receptor via functional coupling between Asn295-mutated receptor and Gpa1/Gi3
      chimeric Galpha.
AB  - Angiotensin II (Ang II) type 1 receptor (AGTR1) is a G-protein-coupled receptor
      (GPCR). Its natural ligand, Ang II, is an important effector molecule controlling
      blood pressure and volume in the cardiovascular system, and is consequently
      involved in various diseases such as hypertension and heart failure. Thus, the
      signaling mediator, AGTR1, is a significant molecular target in medicinal and
      therapeutic fields. Yeast is a useful organism for sensing GPCR signaling because
      it provides a simplified version of the complicated machinery used by mammalian
      cells for signal transduction. Although yeast cells can successfully transmit a
      signal through a variety of human GPCRs expressed in the cell membrane, there
      have been no reports of the functional activation of AGTR1-mediated signaling in
      yeast cells. In the present study, we introduced a single mutation into human
      AGTR1 and used yeast-human chimeric Galpha to exert the functional activation of
      AGTR1 in yeast cells. The engineered yeast cells expressing AGTR1 mutated at
      Asn295 and the chimeric Galpha successfully transmitted the signal inside the
      yeast cells in response to Ang II peptide and its analogs (Ang III and Ang IV
      peptides) added to the assay medium. Further, we demonstrated that the autocrine
      Ang II peptide and its analog, produced and secreted by the engineered yeast
      cells, could by themselves promote AGTR1-mediated signaling. This means that
      screening for agonistic peptides with various sequences from a self-produced
      genetic library would be a viable strategy. Thus, the constructed yeast
      biosensor, integrating an Asn295-mutated AGTR1 receptor, will be valuable in the
      design of drugs to treat AGTR1-related diseases.

PMID- 24890664
TI  - Coordinated plasticity in brainstem and auditory cortex contributes to enhanced
      categorical speech perception in musicians.
AB  - Musicianship is associated with neuroplastic changes in brainstem and cortical
      structures, as well as improved acuity for behaviorally relevant sounds including
      speech. However, further advance in the field depends on characterizing how
      neuroplastic changes in brainstem and cortical speech processing relate to one
      another and to speech-listening behaviors. Here, we show that subcortical and
      cortical neural plasticity interact to yield the linguistic advantages observed
      with musicianship. We compared brainstem and cortical neuroelectric responses
      elicited by a series of vowels that differed along a categorical speech continuum
      in amateur musicians and non-musicians. Musicians obtained steeper identification
      functions and classified speech sounds more rapidly than non-musicians.
      Behavioral advantages coincided with more robust and temporally coherent
      brainstem phase-locking to salient speech cues (voice pitch and formant
      information) coupled with increased amplitude in cortical-evoked responses,
      implying an overall enhancement in the nervous system's responsiveness to speech.
      Musicians' subcortical and cortical neural enhancements (but not behavioral
      measures) were correlated with their years of formal music training. Associations
      between multi-level neural responses were also stronger in musically trained
      listeners, and were better predictors of speech perception than in non-musicians.
      Results suggest that musicianship modulates speech representations at multiple
      tiers of the auditory pathway, and strengthens the correspondence of processing
      between subcortical and cortical areas to allow neural activity to carry more
      behaviorally relevant information. We infer that musicians have a refined
      hierarchy of internalized representations for auditory objects at both pre
      attentive and attentive levels that supplies more faithful phonemic templates to
      decision mechanisms governing linguistic operations. 

PMID- 24890665
TI  - Quantitative morphology in canine cutaneous soft tissue sarcomas.
AB  - Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas
      [fibrosarcoma (n = 8), liposarcoma (n = 8) and haemangiopericytoma (n = 8)], and
      24 dogs with reactive connective tissue lesions [granulation tissue (n = 12) and
      dermal fibrosis (n = 12)] were analysed by computer-assisted nuclear morphometry.
      The studied morphometric parameters were: mean nuclear area (MNA; um(2)), mean
      nuclear perimeter (MNP; um), mean nuclear diameter (MND mean; um), minimum
      nuclear diameter (Dmin; um) and maximum nuclear diameter (Dmax; um). The study
      aimed to evaluate (1) possibility for quantitative differentiation of soft tissue
      sarcomas from reactive connective tissue lesions and (2) by using
      cytomorphometry, to differentiate the various histopathological soft tissue
      sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric
      parameters (except for Dmax) were statistically significantly higher in reactive
      connective tissue processes than in soft tissue sarcomas. At the same time,
      however, there were no considerable differences among the different sarcoma
      subtypes. The results demonstrated that the quantitative differentiation of
      reactive connective tissue processes from soft tissue sarcomas in dogs is
      possible, but the same was not true for the different canine soft tissue sarcoma
      subtypes. Further investigations on this topic are necessary for thorough
      explication of the role of quantitative morphology in the diagnostics of
      mesenchymal neoplasms and tumour-like fibrous lesions in dogs.

PMID- 24890667
TI  - American Society for Apheresis guidelines on the use of apheresis in clinical
      practice: practical, concise, evidence-based recommendations for the apheresis
      practitioner.
AB  - The 6th Guidelines on the use of therapeutic apheresis in clinical practice
      published by the American Society of Apheresis provide practical, concise, and
      evidence based guidance for the apheresis medicine practitioner. The overall
      format of the Guidelines has remained unchanged with the 6th edition, compared to
      the 5th edition, with enhancements in the committee process of creating the
      guidelines. Because of changes in the writing committee structure, a number of
      changes have occurred in the ASFA category and recommendation grade for the use
      of apheresis in the treatment for a number of previously categorized clinical
      indications. In addition, eight new indications for apheresis, twenty three new
      clinical situations for previously categorized diseases, and ten new apheresis
      treatments for previously categorized disorders have been added. The 6th
      Guidelines continue to be an invaluable resource for those involved in apheresis
      medicine.

PMID- 24890666
TI  - Tributyrin supplementation protects mice from acute ethanol-induced gut injury.
AB  - BACKGROUND: Excessive alcohol consumption leads to liver disease. Interorgan
      crosstalk contributes to ethanol (EtOH)-induced liver injury. EtOH exposure
      causes gut dysbiosis resulting in negative alterations in intestinal fermentation
      byproducts, particularly decreased luminal butyrate concentrations. Therefore, in
      the present work, we investigated the effect of butyrate supplementation, in the
      form of trybutyrin, as a prophylactic treatment against EtOH-induced gut injury.
      METHODS: C57BL/6J mice were treated with 3 different EtOH feeding protocols:
      chronic feeding (25 days, 32% of kcal), short-term (2 days, 32%), or acute single
      gavage (5 g/kg). Tributyrin (0.83 to 10 mM) was supplemented either into the
      liquid diet or by oral gavage. Intestinal expression of tight junction (TJ)
      proteins and a butyrate receptor and transporter were evaluated, as well as liver
      enzymes and inflammatory markers. RESULTS: All 3 EtOH exposure protocols reduced
      the expression and co-localization of TJ proteins (ZO-1, occludin) and the
      expression of a butyrate receptor (GPR109A) and transporter (SLC5A8) in the ileum
      and proximal colon. Importantly, tributyrin supplementation protected against
      these effects. Protection of the intestine with tributyrin supplementation was
      accompanied by mitigation of EtOH-induced increases in aspartate aminotransferase
      and inflammatory measures in the short-term and acute EtOH exposure protocols,
      but not after chronic EtOH feeding. CONCLUSIONS: These findings suggest that
      tributyrin supplementation could serve as a prophylactic treatment against gut
      injury caused by short-term EtOH exposure.

PMID- 24890668
TI  - Islet of Langerhans isolation from pediatric and juvenile donor pancreases.
AB  - Islet grafts isolated from young donors allow superior functional outcomes but
      are often associated with poor islet isolation yields. The objective of this
      study was to comparatively analyze the outcomes of islet isolation between young
      and older donors. We retrospectively analyzed 564 pancreas isolations performed
      at our institution. Isolation outcomes were compared between donors aged <=20
      years (n = 42, YD) and >20 years (n = 522, OD). Isolation procedure was identical
      in both groups. Prepurification percentage of embedded islets was higher in YD
      (44.3 +/- 22.7% vs. 24.9 +/- 20.9%, P < 0.001). This led to a lower recovery rate
      in YD (48% vs. 76%, P = 0.002) and hence lower postpurification IEQ/g pancreas in
      YD (2 412 +/- 1 789 IEQ/g vs. 3 194 +/- 1 892 IEQ/g, P = 0.01). Final yield was
      180 982 +/- 128 073 IEQ in YD and 244 167 +/- 134 137 IEQ in OD, (P = 0.006). In
      vitro function was markedly, albeit nonsignificantly, higher in YD (SI: 4.5 +/-
      5.1 vs. 3.0 +/- 5.7, P = 0.350). Proportion of transplanted preparations was
      similar in both groups, 38% (16/42) in YD vs. 43% (224/522) in OD, P = 0.628. In
      spite of isolation and purification difficulties, pancreases from young donors
      allowed similar islet transplantation rates as older donors. Efforts should be
      directed at improving islet extraction in these donors to realize their full
      potential for islet transplantation. 

PMID- 24890669
TI  - Human breast adipose-derived stem cells: characterization and differentiation
      into mammary gland-like epithelial cells promoted by autologous activated
      platelet-rich plasma.
AB  - Human adipose-derived stem cells (ASCs) isolated from various body sites have
      been widely investigated in basic and clinical studies. However, ASCs derived
      from human breast tissue (hbASCs) have not been extensively investigated. In
      order to expand our understanding of hbASCs and examine their potential
      applications in stem cell research and cell-based therapy, hbASCs were isolated
      from discarded surgical fat tissue following reduction mammoplasty and a
      comprehensive characterization of these hbASCs was performed, including analysis
      of their cellular morphology, growth features, cell surface protein markers and
      multilineage differentiation capacity. These hbASCs expressed cluster of
      differentiation (CD)44, CD49d, CD90 and CD105, but did not express CD31 and CD34.
      Subsequently, the hbASCs were differentiated into adipocytes, osteocytes and
      chondrocytes in vitro. In order to examine the potential applications of hbASCs
      in breast reconstruction, an approach to promote in vitro differentiation of
      hbASCs into mammary gland-like epithelial cells (MGECs) was developed using
      activated autologous platelet-rich plasma (PRP). A proliferation phase and a
      subsequent morphological conversion phase were observed during this
      differentiation process. PRP significantly promoted the growth of hbASCs in the
      proliferation phase and increased the eventual conversion rate of hbASCs into
      MGECs. Thus, to the best of our knowledge, the present study provided the first
      comprehensive characterization of hbASCs and validated their multipotency.
      Furthermore, it was revealed that activated autologous PRP was able to enhance
      the differentiation efficiency of hbASCs into MGECs. The present study and other
      studies of hbASCs may aid the development of improved breast reconstruction
      strategies. 

PMID- 24890670
TI  - Airway complication contributing to disseminated fusariosis after lung
      transplantation.
AB  - Fungal infections are common after lung transplantation. However, disseminated
      fusariosis is rare and we report the first case of airway complications
      associated with this infectious process. A 77-year-old Caucasian woman, who was
      status post left single-lung transplant for emphysema, presented to clinic 8
      months after lung transplantation with pleurisy, shortness of breath, and
      declining lung function. Bronchoscopy showed narrowing of the left anastomotic
      site with dynamic compression during exhalation. An AERO stent was deployed
      successfully, but 3 weeks later, her symptoms recurred. Bronchoscopy showed total
      stent occlusion with thick tenacious mucus. Fusarium solani was isolated from
      cultures, and a new 1.5 cm skin nodule was found on the anteromedial midportion
      of the patient's left lower leg. Voriconazole and anidulafungin were started. No
      evidence of mucus accumulation was seen during a follow-up bronchoscopy. It is
      likely that Fusarium infection contributed to the initial anastomotic
      complication as well as to obstruction of the stent. Furthermore, the stent may
      have contributed to establishment and development of disseminated fusariosis.
      With antifungal therapy, stent patency was maintained and the patient improved
      clinically.

PMID- 24890671
TI  - Perceived need for information of patients with haematological malignancies: a
      literature review.
AB  - AIMS AND OBJECTIVES: To provide insight into the perceived need for information
      of patients with haematological malignancies. BACKGROUND: Providing timely and
      accurate information to patients diagnosed with a haematological malignancy is a
      challenge in clinical practice; treatment often has to start promptly, with
      little time to inform patients. DESIGN: Literature review. METHODS: A
      comprehensive literature search was conducted from all available literature to
      May 2013 in the databases: Cumulative Index to Nursing and Allied Health
      Literature, PsycINFO and PubMed (Medline). Relevant studies were reviewed
      regarding the perceived need for information on various topics, sources of
      information and satisfaction with information provided. RESULTS: The initial
      search revealed 215 articles, fourteen of which were relevant. Patients need
      basic information on the disease (diagnosis and diagnostics), treatment (various
      treatment options, side effects and duration), prognosis (curability and
      prolonging life) and all other topics (recovery, self-care and psychosocial
      functioning). Need for detailed information varied between studies. Patients
      expressed a higher need for medical than for psychosocial information. Patients
      preferred to receive information from their doctors the most, followed by nurses.
      Most studies described patients' satisfaction with the information provided.
      CONCLUSION: Based on the limited number of data available, medical information is
      for patients of higher priority compared to psychosocial information. Patients
      need basic information on diagnosis, treatment, prognosis and all other topics.
      Need for detailed information varied between studies. Patients were satisfied
      with the provided information, preferably offered by doctors and nurses.
      RELEVANCE TO CLINICAL PRACTICE: The perceived need for information and
      satisfaction with the information provided differs strongly between patients. In
      clinical practice, more attention is needed for information tailored to the
      patient, taking into account important moderating factors such as age, type of
      cancer, time since diagnosis, treatment modality and coping style.

PMID- 24890672
TI  - Concomitant dental injuries in maxillofacial fractures - a retrospective analysis
      of 1219 patients.
AB  - BACKGROUND/AIM: Traumatic dental injuries are frequently combined with
      maxillofacial fractures, but literature addressing this topic is rare. In a
      retrospective study, the frequency of dental lesions in inpatients with traumatic
      facial injuries was analyzed. MATERIAL AND METHODS: All patients referred to the
      Department of Oral and Maxillofacial Surgery of the University Medical Center of
      the Johannes Gutenberg-University Mainz for inpatient treatment due to facial
      fractures between January 2001 and December 2007 were analyzed regarding the type
      of fracture, its localization, and potential concomitant dental injuries. In
      addition a systematic review was performed to compare the findings of this study
      with existing data. RESULTS: Altogether 1219 facial trauma patients underwent
      inpatient treatment. 184 (15.87%) out of those had 451 injured teeth, and 4.9%
      were edentulous. The most frequent causes were assaults (25.1%), followed by
      falls (19.6%) and bike accidents (10.1%). Avulsion, especially of the upper
      incisors, occurred in most cases (27.9%). Assaults caused 1.29 dental fractures
      per patient, while traffic-related accidents led to three to four times higher
      injury-rates. CONCLUSIONS: With almost every sixth patient having at least one
      kind of dental injury, this study shows that a thorough anamnesis and examination
      of the dental status are absolutely necessary, especially in patients who
      suffered from high-speed impacts or collisions with low-resilience surfaces.

PMID- 24890674
TI  - A statistical model to predict the reduction of lichenification in atopic
      dermatitis.
AB  - Acute symptoms of atopic dermatitis (AD), such as erythema, oedema/papulations
      and excoriations, respond quickly to topical corticosteroid treatment.
      Conversely, lichenification is regarded as a troublesome non-acute symptom of
      chronic AD which can take months of treatment before any improvement is seen.
      However, very little data actually support this opinion. Here, we analyse
      lichenification scores in 3 multicentre, short-term studies of nearly similar
      design. Two of these studies were active comparator dosage trials administered
      with either fluticasone propionate cream or ointment once or twice daily, the
      third study was a placebo control. In each of these 4-weeks studies
      lichenification was measured weekly. For the evaluation of the lichenification
      score over time a random-coefficients regression model was used. In all active
      treatments lichenification significantly improved (p < 0.005) within one week.
      Improvement continued afterwards, with > 80% of patients scoring no, very mild or
      mild lichenification after 4 weeks. We developed a model in which the
      lichenification score drops off linearly with the square root of time. The
      resulting convexly shaped downward time trend of lichenification was significant
      during all treatments and was significantly stronger during active treatment than
      with placebo. Fluticasone propionate can improve moderate to severe
      lichenification in a relative short period of time. 

PMID- 24890673
TI  - Functional outcome and quality of life after rehabilitation for voluntary
      posterior shoulder dislocation: a prospective blinded cohort study.
AB  - BACKGROUND: Voluntary posterior instability of the shoulder is a rare condition
      in which the patient is able to cause a subluxation by voluntary muscle
      activation. A shoulder rehabilitation program aimed to correct abnormal muscle
      patterns and restore correct scapular motion may provide good results and improve
      the quality of life of these patients. METHODS: Fifteen subjects (six males, nine
      females; mean age 19 years) underwent physical examination and clinical tests
      [Disability of the Arm, Shoulder and Hand (DASH) score, Shoulder Pain and
      Disability Index (SPADI), and modified Rowe score] and compiled the patient
      global assessment (PGA). Articular or rotator cuff lesions were excluded by X
      rays and MRI. The rehabilitation program included three phases: (1) assessment
      and correction of abnormal muscle patterns, (2) restoration of correct scapular
      motion, and (3) strengthening of scapular and posterior glenohumeral muscles.
      Follow-up was at 3, 6, 12, and 24 months. RESULTS: DASH and SPADI scores improved
      significantly at 3 (p < 0.01), 6 (p < 0.009), 12 (p < 0.001), and 24 months (p <
      0.001). The Rowe score was fair at 3 months and good at 6, 12, and 24 months.
      Active flexion, abduction, and external rotation increased at all follow-up
      points (p < 0.01), whereas internal rotation remained unchanged (p > 0.05). PGA
      values were high. Compliance was good without serious adverse events reported
      during the treatment. A correlation was found between age and DASH changes
      (Spearman's rho -0.56; p = 0.0455). CONCLUSIONS: Our findings stress the value of
      a rehabilitation program that teaches subjects with voluntary instability how to
      correct abnormal muscle patterns to restore scapular motion, and the importance
      of adopting home rehabilitation exercises as a part of the normal lifestyle.

PMID- 24890675
TI  - Preparation and regioselective metalation of bis(trimethylsilyl)methyl
      substituted aryl derivatives.
AB  - A range of bis(trimethylsilyl)methyl-substituted aryl derivatives was prepared by
      using a Kumada-Corriu cross-coupling reaction. The regioselective metalation of
      the resulting bis(trimethylsilyl)methyl-substituted aryl derivatives bearing this
      bulky silyl group allowed the generation of functionalized aromatics. A
      regioselective switch in the presence or in the absence of the
      bis(trimethylsilyl)methyl group has been demonstrated. Furthermore, this silyl
      group was converted into a formyl group or a styryl group, enhancing the scope of
      application of such bis(trimethylsilyl)methyl-substituted arenes. 

PMID- 24890676
TI  - Maternal caffeine exposure impairs insulin secretion by pancreatic beta-cells and
      increases the risk of type II diabetes mellitus in offspring.
AB  - Maternal caffeine exposure may be one of the causes for intrauterine growth
      retardation and low birth weight (LBW), and increased risk of type 2 diabetes
      mellitus (T2DM) in the adulthood has been associated with LBW. However, whether
      maternal caffeine exposure contributes to T2DM development of her offspring has
      not been fully investigated. We have investigated the influence of maternal
      caffeine exposure on glucose homeostasis in vivo and effects of long-term
      caffeine load on insulin secretion of beta-cells. The intake of caffeine during
      gestation markedly decreases birth weight and postnatal body weight of the
      offspring. Serum insulin levels of adult offspring after oral glucose tolerance
      test (OGTT) were significantly lower in the caffeine group compared to the
      control, although plasma glucose levels were not significantly altered. Proteome
      analysis of pancreas of adult offspring identified 24 proteins that were
      differentially expressed between the caffeine and control groups, including
      proteins involved in energy metabolism. In a rat pancreatic beta-cell line Rin-5f
      cells, caffeine downregulated expression of one of the proteins involved in
      insulin synthesis, P4hb, and there was reduced transcriptional expression of
      insulin. While basal insulin secretion of caffeine-treated cells was elevated,
      insulin secretion after glucose challenge in long-term caffeine-treated cells was
      significantly reduced, with increased apoptosis of beta-cells. These results
      indicate that maternal caffeine exposure may result in potentially abnormal
      glucose homeostasis and increase the risk of T2DM in the offspring adulthood. 

PMID- 24890677
TI  - Inverse association between diabetes and altitude: a cross-sectional study in the
      adult population of the United States.
AB  - OBJECTIVE: To determine whether geographical elevation is inversely associated
      with diabetes, while adjusting for multiple risk factors. METHODS: This is a
      cross-sectional analysis of publicly available online data from the Behavioral
      Risk Factor Surveillance System, 2009. Final dataset included 285,196 US adult
      subjects. Odds ratios were obtained from multilevel mixed-effects logistic
      regression analysis. RESULTS: Among US adults (>=20 years old), the odds ratio
      for diabetes was 1.00 between 0 and 499 m of altitude (reference), 0.95 (95%
      confidence interval, 0.90-1.01) between 500 and 1,499 m, and 0.88 (0.81-0.96)
      between 1,500 and 3,500 m, adjusting for age, sex, body mass index, ethnicity,
      self-reported fruit and vegetable consumption, self-reported physical activity,
      current smoking status, level of education, income, health status, employment
      status, and county-level information on migration rate, urbanization, and
      latitude. The inverse association between altitude and diabetes in the US was
      found among men [0.84 (0.76-0.94)], but not women [1.09 (0.97-1.22)].
      CONCLUSIONS: Among US adults, living at high altitude (1,500-3,500 m) is
      associated with lower odds of having diabetes than living between 0 and 499 m,
      while adjusting for multiple risk factors. Our findings suggest that geographical
      elevation may be an important factor linked to diabetes.

PMID- 24890679
TI  - Re: osteochondral transplantation for the treatment of osteochondral defects at
      the talus with the Diamond twin system((r)) and graft harvesting from the
      posterior femoral condyles.

PMID- 24890678
TI  - Stem cells loaded with nanoparticles as a drug carrier for in vivo breast cancer
      therapy.
AB  - A novel anti-cancer drug carrier, mesenchymal stem cells (MSCs) encapsulating
      drug-loaded hollow silica nanoparticles, is used to carry a photosensitizer drug
      and deliver it to breast tumors, due to the natural high tumor affinity of the
      MSCs, and inhibit tumor growth by photo dynamic therapy. This new strategy for
      delivering a photo sensitizer to tumors by using tumor-affinitive MSCs addresses
      the challenge of the accumulation of photosensitizer drugs in tumors in
      photodynamic therapy. 

PMID- 24890680
TI  - Disseminated herpes simplex virus manifesting as pyrexia and cervicitis and
      leading to reactive hemophagocytic syndrome in pregnancy.

PMID- 24890681
TI  - Obstetrics and gynaecology training in Europe needs a next step.
AB  - Changing societal demands on doctors necessitate changes in the training of
      gynaecologists. Adapting this training will need well-thought-out and
      comprehensive planning that addresses the needs of the major stakeholders:
      society, patients, and doctors themselves. Doctors need to be cognizant of
      societal issues such as rapidly rising healthcare costs and budgetary crises, and
      be able to participate in the solutions. This demands effective medical
      leadership, which has been a neglected area in postgraduate training. It has
      become increasingly evident that a holistic view of the patient rooted in proper
      teamwork and systems-based practice is essential to provide patient-centered
      care. Specialists need to expand their skill set to participate in this kind of
      care. Furthermore, the feminisation of the medical profession and a new
      generation of doctors rejecting the constraints of the traditional model of
      medical care introduce new professional perspectives. This manuscript briefly
      reviews the challenges faced in the training of European gynaecologists in an
      effort to provoke discussion about how to best train the gynaecologists of the
      future. 

PMID- 24890682
TI  - Endometriosis and susceptibility to multiple sclerosis: is there any absolute
      truth?

PMID- 24890683
TI  - Dapagliflozin added to usual care in individuals with type 2 diabetes mellitus
      with preexisting cardiovascular disease: a 24-week, multicenter, randomized,
      double-blind, placebo-controlled study with a 28-week extension.
AB  - OBJECTIVES: To assess the efficacy of dapagliflozin, a sodium-glucose
      cotransporter 2 inhibitor, for the treatment of individuals with type 2 diabetes
      mellitus (T2DM) and preexisting cardiovascular disease (CVD). DESIGN: Randomized,
      double-blind, age-stratified (<65 and >= 65), 24-week clinical trial with a 28
      week extension. SETTING: One hundred seventy-three centers in 10 countries.
      PARTICIPANTS: Individuals (N = 964) with T2DM, glycosylated hemoglobin (HbA1c) of
      7.0% to 10.0%, and documented CVD. INTERVENTION: Dapagliflozin 10 mg/d or placebo
      was added to usual care. Participants receiving insulin had their total daily
      insulin dose reduced by 25% at randomization. MEASUREMENTS: Two equal primary end
      points: change from baseline in HbA1c and proportion of participants achieving a
      three-item end point (reduction of >= 0.5% in HbA1c, >= 3% in body weight, and >=
      3 mmHg in systolic blood pressure) at 24 weeks. RESULTS: Forty-seven percent were
      aged 65 and older, 7.7% were aged 75 and older, mean duration of T2DM was 13
      years, mean baseline HbA1c was 8.1%, and approximately 60% were taking insulin.
      The placebo-corrected change in HbA1c with dapagliflozin was -0.4% at 24 weeks.
      Significantly more participants achieved the three-item end point with
      dapagliflozin (10.0%) than with placebo (1.9%). The placebo-corrected percentage
      change in body weight for dapagliflozin was -1.9% (-1.8 kg). Similar results were
      observed in both age strata, and changes were maintained over 52 weeks. More than
      one-quarter (28.2%) of participants receiving dapagliflozin and 25.3% of those
      receiving placebo experienced hypoglycemia. More participants receiving
      dapagliflozin had vulvovaginitis, balanitis, or urinary tract infection.
      CONCLUSION: When added to a usual background regimen in an older population with
      advanced T2DM and preexisting comorbid CVD, dapagliflozin improved glycemic
      control without an increase in hypoglycemic risk, promoted weight loss, and was
      well tolerated.

PMID- 24890685
TI  - When nonspecific histology can be a clue to the diagnosis: three cases of
      trigeminal trophic syndrome.
AB  - Trigeminal trophic syndrome (TTS) is a rare cause of facial ulceration, which is
      usually associated with damage to the trigeminal nerve pathway, either centrally
      or peripherally, the most common causes being cerebrovascular accidents and
      trigeminal nerve ablation procedures. We present three cases of TTS, emphasizing
      the histopathological features. All three patients presented with facial
      ulceration. Two patients had a single lesion, and the third had several ulcers.
      However, in all cases, there was involvement of the nasal ala, and the lesions
      were strictly unilateral. Histology consistently showed ulceration with signs of
      severe chronic trauma: scarring, lichenification and/or pseudoepitheliomatous
      hyperplasia. Diagnosis of TTS can be difficult, and requires close
      clinicopathological correlation. Histology is important in excluding the majority
      of possible conditions included in the differential diagnosis, mainly malignancy
      and infectious processes. Several treatments have been described, but TTS is
      frequently refractory to treatment. 

PMID- 24890684
TI  - Low-grade prostate cancer diverges early from high grade and metastatic disease.
AB  - Understanding the developmental relationship between indolent and aggressive
      tumors is central to understanding disease progression and making treatment
      decisions. For example, most men diagnosed with prostate cancer have clinically
      indolent disease and die from other causes. Overtreatment of prostate cancer
      remains a concern. Here we use laser microdissection followed by exome sequencing
      of low- and high-grade prostate cancer foci from four subjects, and metastatic
      disease from two of those subjects, to evaluate the molecular relationship of
      coincident cancer foci. Seventy of 79 (87%) high-confidence somatic mutations in
      low-grade disease were private to low-grade foci. In contrast, high-grade foci
      and metastases harbored many of the same mutations. In cases in which there was a
      metastatic focus, 15 of 80 (19%) high-confidence somatic mutations in high-grade
      foci were private. Seven of the 80 (9%) were shared with low-grade foci and 65
      (82%) were shared with metastatic foci. Notably, mutations in cancer-associated
      genes and the p53 signaling pathway were found exclusively in high-grade foci and
      metastases. The pattern of mutations is consistent with early divergence between
      low- and high-grade foci and late divergence between high-grade foci and
      metastases. These data provide insights into the development of high-grade and
      metastatic prostate cancer. 

PMID- 24890686
TI  - Recognition of music and melody in patients with cochlear implants, using a new
      programming approach for frequency assignment.
AB  - INTRODUCTION AND OBJECTIVE: Music is a universal, cross-cultural phenomenon.
      Perception and enjoyment of music are still not solved with current technological
      objectives of cochlear implants. The objective of this article was to advance the
      development and validation of a method of programming of cochlear implants that
      implements a frequency allocation strategy. We compared standard programming vs
      frequency programming in every subject. METHODS: We studied a total of 40
      patients with cochlear implants. Each patient was programmed with a optimal
      version of the standard program, using the Custom Sound Suite 3.2 cochlear
      platform. Speech tests in quiet were performed using syllable word lists from the
      protocol for the assessment of hearing in the Spanish language. Patients
      implanted bilaterally were tested in both ears at the same time. For assessing
      music listening habits we used the Munich Music Questionnaire and
      "MACarena"(minimum auditory capability) software. RESULTS: All patients achieved
      better results in recognition, instrument tests and tonal scales with frequency
      programming (P<.005). Likewise, there were better results with frequency
      programming in recognising harmonics and pitch test (P<.005). CONCLUSIONS:
      Frequency programming achieves better perception and recognition results in
      patients in comparison with standard programming. Bilateral stimulation patients
      have better perception of musical patterns and better performance in recognition
      of tonal scales, harmonics and musical instruments compared with patients with
      unilateral stimulation. Modification and frequency allocation during programming
      allows decreased levels of current intensity and increase the dynamic range,
      which allows mapping of each audio band less obtrusively and improves the quality
      of representation of the signal.

PMID- 24890687
TI  - Parenteral antiretroviral formulations are still urgently needed: a case report
      and commentary.
AB  - This case report highlights a challenging clinical dilemma to administer
      antiretroviral therapy in a critically-ill human immunodeficiency virus-infected
      patient who presented with multiple opportunistic infections and a non-functional
      gastrointestinal tract. The need for parenteral antiretroviral drug options is
      discussed and investigational drugs are briefly reviewed. 

PMID- 24890688
TI  - Decatenation checkpoint-defective melanomas are dependent on PI3K for survival.
AB  - Melanoma cell lines are commonly defective for the G2-phase cell cycle checkpoint
      that responds to incomplete catenation of the replicated chromosomes. Here, we
      demonstrate that melanomas defective for this checkpoint response are less
      sensitive to genotoxic stress, suggesting that the defective cell lines
      compensated for the checkpoint loss by increasing their ability to cope with DNA
      damage. We performed an siRNA kinome screen to identify kinases responsible and
      identified PI3K pathway components. Checkpoint-defective cell lines were three
      fold more sensitive to small molecule inhibitors of PI3K. The PI3K inhibitor PF
      05212384 promoted apoptosis in the checkpoint-defective lines, and the increased
      sensitivity to PI3K inhibition correlated with increased levels of activated Akt.
      This work demonstrates that increased PI3K pathway activation is a necessary
      adaption for the continued viability of melanomas with a defective decatenation
      checkpoint. 

PMID- 24890689
TI  - Bimodal mortality dynamics for uveal melanoma: a cue for metastasis development
      traits?
AB  - BACKGROUND: The study estimates mortality dynamics (event-specific hazard rates
      over a follow-up time interval) for uveal melanoma. METHODS: Three thousands six
      hundred seventy two patients undergoing radical or conservative treatment for
      unilateral uveal melanoma, whose yearly follow-up data were reported in three
      published datasets, were analysed. Mortality dynamics was studied by estimating
      with the life-table method the discrete hazard rate for death. Smoothed curves
      were obtained by a Kernel-like smoothing procedure and a piecewise exponential
      regression model. The ratio deaths/patients at risk per year was the main outcome
      measure. RESULTS: The three explored hazard rate curves display a common bimodal
      pattern, with a sudden increase peaking at about three years, followed by
      reduction until the sixth-seventh year and a second surge peaking at about nine
      years after treatment. CONCLUSIONS: The bimodal pattern of mortality indicates
      that uveal melanoma metastatic development cannot be explained by a continuous
      growth model. Similar metastasis dynamics have been reported for other tumours,
      including early breast cancer, for which it supported a paradigm shift to an
      interrupted growth model, the implications of which are episodes of 'tumour
      dormancy'. We propose that the concepts of tumour homeostasis, tumour dormancy
      and enhancement of metastasis growth related to primary tumour removal,
      convincingly explaining the clinical behaviour of breast cancer, may be used for
      uveal melanoma as well. To confirm this proposition, a careful analysis of uveal
      melanoma metastasis dynamics is strongly warranted.

PMID- 24890690
TI  - Solvent effect on the vibrational spectrum of Michler's ketone. Experimental and
      theoretical investigations.
AB  - We examined solvent effect on the IR and Raman spectra of MK in several solvents
      of different polarity and proticity, for understanding of intermolecular
      interactions, focusing on solvent effect in detail. It has been found that change
      of solvent polarity has an ambiguous influence on solvatochromism of MK. We have
      observed that not only vibrations of carbonyl group are affected by the solvent
      polarity, but also mode nu(CN) and nu(CC) in IR and Raman spectra of MK.
      Experimental investigations have been supported by the quantum-mechanical
      computations to gain more insight into the solvatochromic behavior of Michler's
      ketone. Calculations have been carried using Kohn-Sham formulation of Density
      Functional Theory (DFT) and the Polarizable Continuum Model (PCM) was employed to
      account for solute solvent interactions. 

PMID- 24890691
TI  - Lanthanide upconversion nanoparticles and applications in bioassays and
      bioimaging: a review.
AB  - Through the process of photon upconversion, trivalent lanthanide doped
      nanocrystals convert long-wavelength excitation radiation in the infrared or near
      infrared region to higher energy emission radiation from ultraviolet to infrared.
      Such materials offer potential for numerous advantages in analytical applications
      in comparison to molecular fluorophores and quantum dots. The use of IR radiation
      as an excitation source reduces autofluorescence and scattering of excitation
      radiation, which leads to a reduction of background in optical experiments. The
      upconverting nanocrystals offer excellent photostability and are composed of
      materials that are not particularly toxic to biological organisms. Excitation at
      long wavelengths also minimizes damage to biological materials. In this review,
      the different mechanisms responsible for the upconversion process, and methods
      that are used to synthesize and decorate upconverting nanoparticles are presented
      to indicate how absorption and emission can be tuned. Examples of recent
      applications of upconverting nanoparticles in bioassays for the detection of
      proteins, nucleic acids, metabolites and metal ions offer indications of
      analytical advantages in the development of methods of analysis. Examples include
      multi-color and multi-modal imaging, and the use of upconverting nanoparticles in
      theranostics. 

PMID- 24890692
TI  - Facile fabrication of nanoporous PdFe alloy for nonenzymatic electrochemical
      sensing of hydrogen peroxide and glucose.
AB  - Nanoporous (NP) PdFe alloy is easily fabricated through one step mild dealloying
      of PdFeAl ternary source alloy in NaOH solution. Electron microscopy
      characterization demonstrates that selectively dissolving Al from PdFeAl alloy
      generates three-dimensional bicontinuous nanospongy architecture with the typical
      ligament size around 5 nm. Electrochemical measurements show that the NP-PdFe
      alloy exhibits the superior electrocatalytic activity and durability towards
      hydrogen peroxide (H2O2) detection compared with NP-Pd and commercial Pd/C
      catalysts. In addition, NP-PdFe performs high sensing performance towards H2O2 in
      a wide linear range from 0.5 to 6 mM with a low detection limit of 2.1 MUM. This
      nanoporous structure also can sensitively detect glucose over a wide
      concentration range (1-32 mM) with a low detection limit of 1.6 MUM and high
      resistance against chloride ions. Along with these attractive features, the as
      made NP-PdFe alloy also has a good anti-interference towards ascorbic acid, uric
      acid, and dopamine.

PMID- 24890693
TI  - Reusable conductimetric array of interdigitated microelectrodes for the readout
      of low-density microarrays.
AB  - Low-density protein microarrays are emerging tools in diagnostics whose
      deployment could be primarily limited by the cost of fluorescence detection
      schemes. This paper describes an electrical readout system of microarrays
      comprising an array of gold interdigitated microelectrodes and an array of
      polydimethylsiloxane microwells, which enabled multiplexed detection of up to
      thirty six biological events on the same substrate. Similarly to fluorescent
      readout counterparts, the microarray can be developed on disposable glass slide
      substrates. However, unlike them, the presented approach is compact and requires
      a simple and inexpensive instrumentation. The system makes use of urease labeled
      affinity reagents for developing the microarrays and is based on detection of
      conductivity changes taking place when ionic species are generated in solution
      due to the catalytic hydrolysis of urea. The use of a polydimethylsiloxane
      microwell array facilitates the positioning of the measurement solution on every
      spot of the microarray. Also, it ensures the liquid tightness and isolation from
      the surrounding ones during the microarray readout process, thereby avoiding
      evaporation and chemical cross-talk effects that were shown to affect the
      sensitivity and reliability of the system. The performance of the system is
      demonstrated by carrying out the readout of a microarray for boldenone anabolic
      androgenic steroid hormone. Analytical results are comparable to those obtained
      by fluorescent scanner detection approaches. The estimated detection limit is 4.0
      ng mL(-1), this being below the threshold value set by the World Anti-Doping
      Agency and the European Community.

PMID- 24890694
TI  - A novel electrochemical aptasensor for highly sensitive detection of thrombin
      based on the autonomous assembly of hemin/G-quadruplex horseradish peroxidase
      mimicking DNAzyme nanowires.
AB  - In this work, a new signal amplified strategy was constructed based on isothermal
      exponential amplification reaction (EXPAR) and hybridization chain reaction (HCR)
      generating the hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme (HRP
      mimicking DNAzyme) nanowires as signal output component for the sensitive
      detection of thrombin (TB). We employed EXPAR's ultra-high amplification
      efficiency to produce a large amount of two hairpin helper DNAs within a minutes.
      And then the resultant two hairpin helper DNAs could autonomously assemble the
      hemin/G-quadruplex HRP-mimicking DNAzymes nanowires as the redox-active reporter
      units on the electrode surface via hybridization chain reaction (HCR). The
      hemin/G-quadruplex structures simultaneously served as electron transfer medium
      and electrocatalyst to amplify the signal in the presence of H2O2. Specifically,
      only when the EXPAR reaction process has occurred, the HCR could be achieved and
      the hemin/G-quadruplex complexes could be formed on the surface of an electrode
      to give a detectable signal. The proposed strategy combines the amplification
      power of the EXPAR, HCR, and the inherent high sensitivity of the electrochemical
      detection. With such design, the proposed assay showed a good linear relationship
      within the range of 0.1 pM-50 nM with a detection limit of 33 fM (defined as
      S/N=3) for TB.

PMID- 24890695
TI  - Restricted access chiral stationary phase synthesized via reversible addition
      fragmentation chain-transfer polymerization for direct analysis of biological
      samples by high performance liquid chromatography.
AB  - Novel hydrophilic microparticles containing beta-cyclodextrin (beta-CD) were
      prepared via one-pot synthesis using reversible addition-fragmentation chain
      transfer (RAFT) precipitation polymerization, a "controlled/living" radical
      polymerization technique. The polymerization was initiated by hydrophilic
      macromolecular chain-transfer agent [poly(2-hydroxyethyl methacrylate), PHEMA].
      The hydrophilic PHEMA on the surface of microparticles can well improve their
      surface hydrophilicity and lead to their biological compatibility. As chiral
      restricted access material (RAM), the hydrophilic microparticles can be used for
      determination of enantiomers in biological samples with direct injection via HPLC
      analysis. 

PMID- 24890696
TI  - Off-label use of recombinant activated factor VII in surgical and non-surgical
      patients at 16 Canadian hospitals from 2007 to 2010 (Canadian Registry Report).
AB  - PURPOSE: Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that
      is approved for treatment of bleeding in hemophilia patients, but it is
      frequently used off-label in non-hemophiliacs. The purpose of this study was to
      determine if the off-label use of rFVIIa is expanding and whether this poses a
      net harm to patients. METHODS: For this historical cohort study, data were
      collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at
      16 Canadian centres, and the pattern of use was examined. Logistic regression was
      used to determine the prognostic importance of severity of bleeding and the
      presence of an rFVIIa dose-effect relationship with major adverse events.
      RESULTS: One thousand three hundred seventy-eight patients received rFVIIa off
      label, and 987 (72%) of these patients underwent cardiac surgery. The median
      [interquartile range] dose was 57 [36-85] ug.kg(-1). Usage increased from 2007 to
      2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and
      307, respectively). Dose of rFVIIa and bleeding severity were associated with
      measured adverse events (P < 0.05). After adjusting for bleeding severity, dose
      was not associated with any of the adverse events. CONCLUSIONS: The off-label use
      of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically
      important, the benefits of rapidly gaining control of bleeding that is non
      responsive to conventional therapies may at times warrant the use of potent
      hemostatic drugs with established risk profiles, such as rFVIIa.

PMID- 24890698
TI  - Induced-fit mechanism in class I terpene cyclases.
AB  - We present crystallographic and functional data of selina-4(15),7(11)-diene
      synthase (SdS) from Streptomyces pristinaespiralis in its open and closed (ligand
      bound) conformation. We could identify an induced-fit mechanism by elucidating a
      rearrangement of the G1/2 helix-break motif upon substrate binding. This
      rearrangement highlights a novel effector triad comprising the pyrophosphate
      sensor Arg178, the linker Asp181, and the effector Gly182-O. This structural
      motif is strictly conserved in class I terpene cyclases from bacteria, fungi, and
      plants, including epi-isozizaene synthase (3KB9), aristolochene synthase (4KUX),
      bornyl diphosphate synthase (1N20), limonene synthase (2ONG), 5-epi-aristolochene
      synthase (5EAT), and taxa-4(5),11(12)-diene synthase (3P5R). An elaborate
      structure-based mutagenesis in combination with analysis of the distinct product
      spectra confirmed the mechanistic models of carbocation formation and
      stabilization in SdS. 

PMID- 24890699
TI  - Association between dental caries and obesity evaluated by air displacement
      plethysmography in 18-year-old adolescents in Pelotas, Brazil.
AB  - OBJECTIVES: To investigate the association between dental caries and obesity,
      evaluated by air displacement plethysmography, among 18-year-old adolescents from
      a birth cohort in the city of Pelotas, Brazil. METHODS: A cross-sectional study
      nested in a birth cohort study was conducted in Pelotas, Brazil. A random sample
      of 986 18-year-old adolescents was selected. The outcome variable was the
      occurrence of dental caries (DMFT >= 1) according to clinical examination by a
      trained and calibrated dentist. For the exposure variable (obesity), body fat
      percentage was measured using air displacement plethysmography and classified as
      normal weight (<P85), overweight (P85-P95), and obesity (>P95). Sociodemographic
      and behavior variables were collected using a questionnaire. We performed
      multivariable Poisson regression analyses with robust variance to examine the
      association between dental caries and obesity. RESULTS: DMFT ranged from 0 to 19;
      mean (SD) was 2 (2.3), and median (P25-P75) was 1 (0-3). Body fat percentage
      ranged from 0.9 to 57.6%; mean (SD) percentage was 24.4% (11.6%), and median (P25
      P75) was 25.1% (14.0-32.9%). The prevalence of dental caries was 66.5% (95% CI
      63.6-69.5%), being significantly higher in female adolescents with lower maternal
      education, lower education, and sugar intake more than once a day. There were no
      differences in the probability of dental caries among individuals with normal
      weight, overweight, or obesity in the unadjusted model (P = 0.846) or after
      adjustment for sociodemographic (P = 0.864) variables. CONCLUSIONS: Overweight
      and obesity were not associated with the occurrence of dental caries in 18-year
      old adolescents.

PMID- 24890700
TI  - Nestling rearing is antioxidant demanding in female barn swallows (Hirundo
      rustica).
AB  - Reproduction is a demanding activity, since organisms must produce and, in some
      cases, protect and provision their progeny. Hence, a central tenet of life
      history theory predicts that parents have to trade parental care against body
      maintenance. One physiological cost thought to be particularly important as a
      modulator of such trade-offs is oxidative stress. However, evidence in favour of
      the hypothesis of an oxidative cost of reproduction is contradictory. In this
      study, we manipulated the brood size of wild barn swallows Hirundo rustica soon
      after hatching of their nestlings to test whether an increase in nestling rearing
      effort translates into an increased oxidative damage and a decreased antioxidant
      protection at the end of the nestling rearing period. We found that, while plasma
      oxidative damage was unaffected by brood size enlargement, females rearing
      enlarged broods showed a decrease in plasma non-enzymatic antioxidants during the
      nestling rearing period. This was not the case among females rearing reduced
      broods and among males assigned to either treatment. Moreover, individuals with
      higher plasma oxidative damage soon after the brood size manipulation had lower
      plasma non-enzymatic antioxidants at the end of the nestling rearing period,
      suggesting that non-enzymatic antioxidants were depleted to buffer the negative
      effects of high oxidative damage. Our findings point to antioxidant depletion as
      a potential mechanism mediating the cost of reproduction among female birds. 

PMID- 24890697
TI  - Analytical challenges translating mass spectrometry-based phosphoproteomics from
      discovery to clinical applications.
AB  - Phosphoproteomics is the systematic study of one of the most common protein
      modifications in high throughput with the aim of providing detailed information
      of the control, response, and communication of biological systems in health and
      disease. Advances in analytical technologies and strategies, in particular the
      contributions of high-resolution mass spectrometers, efficient enrichments of
      phosphopeptides, and fast data acquisition and annotation, have catalyzed
      dramatic expansion of signaling landscapes in multiple systems during the past
      decade. While phosphoproteomics is an essential inquiry to map high-resolution
      signaling networks and to find relevant events among the apparently ubiquitous
      and widespread modifications of proteome, it presents tremendous challenges in
      separation sciences to translate it from discovery to clinical practice. In this
      mini-review, we summarize the analytical tools currently utilized for
      phosphoproteomic analysis (with focus on MS), progresses made on deciphering
      clinically relevant kinase-substrate networks, MS uses for biomarker discovery
      and validation, and the potential of phosphoproteomics for disease diagnostics
      and personalized medicine. 

PMID- 24890701
TI  - Silver deposition on titanium surface by electrochemical anodizing process
      reduces bacterial adhesion of Streptococcus sanguinis and Lactobacillus
      salivarius.
AB  - OBJECTIVES: The aim of this study was to determine the antibacterial properties
      of silver-doped titanium surfaces prepared with a novel electrochemical anodizing
      process. MATERIAL AND METHODS: Titanium samples were anodized with a pulsed
      process in a solution of silver nitrate and sodium thiosulphate at room
      temperature with stirring. Samples were processed with different electrolyte
      concentrations and treatment cycles to improve silver deposition. Physicochemical
      properties were determined by X-ray photoelectron spectroscopy, contact angle
      measurements, white-light interferometry, and scanning electron microscopy.
      Cellular cytotoxicity in human fibroblasts was studied with lactate dehydrogenase
      assays. The in vitro effect of treated surfaces on two oral bacteria strains
      (Streptococcus sanguinis and Lactobacillus salivarius) was studied with viable
      bacterial adhesion measurements and growth curve assays. Nonparametric
      statistical Kruskal-Wallis and Mann-Whitney U-tests were used for multiple and
      paired comparisons, respectively. Post hoc Spearman's correlation tests were
      calculated to check the dependence between bacteria adhesion and surface
      properties. RESULTS: X-ray photoelectron spectroscopy results confirmed the
      presence of silver on treated samples and showed that treatments with higher
      silver nitrate concentration and more cycles increased the silver deposition on
      titanium surface. No negative effects in fibroblast cell viability were detected
      and a significant reduction on bacterial adhesion in vitro was achieved in silver
      treated samples compared with control titanium. CONCLUSIONS: Silver deposition on
      titanium with a novel electrochemical anodizing process produced surfaces with
      significant antibacterial properties in vitro without negative effects on cell
      viability.

PMID- 24890703
TI  - Versatile types of polysaccharide-based supramolecular polycation/pDNA nanoplexes
      for gene delivery.
AB  - Different polysaccharide-based supramolecular polycations were readily
      synthesized by assembling multiple beta-cyclodextrin-cored star polycations with
      an adamantane-functionalized dextran via host-guest interaction in the absence or
      presence of bioreducible linkages. Compared with nanoplexes of the starting star
      polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited
      similarly low cytotoxicity, improved cellular internalization and significantly
      higher gene transfection efficiencies. The incorporation of disulfide linkages
      imparted the supramolecular polycation/pDNA nanoplexes with the advantage of
      intracellular bioreducibility, resulting in better gene delivery properties. In
      addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes
      were also investigated using a suicide gene therapy system. The present study
      demonstrates that the proper assembly of cyclodextrin-cored polycations with
      adamantane-functionalized polysaccharides is an effective strategy for the
      production of new nanoplex delivery systems. 

PMID- 24890702
TI  - Let-7 microRNA-binding-site polymorphism in the 3'UTR of KRAS and colorectal
      cancer outcome: a systematic review and meta-analysis.
AB  - There is a small but growing body of literature regarding the predictive utility
      of a Let-7 microRNA-binding-site polymorphism in the 3'-untranslated region (UTR)
      of KRAS (KRAS-LCS6) for colorectal cancer outcome, although the results are
      conflicting. We performed a review and meta-analysis in an attempt to better
      clarify this relationship. A PubMed search was conducted to identify all studies
      reporting on KRAS let-7 microRNA-binding site polymorphism (LCS6; rs61764370) and
      colorectal cancer outcome. Hazard ratios (HR) and corresponding 95% confidence
      intervals (CI) were extracted or estimated from each manuscript. Log HRs and log
      CIs were combined across studies using the inverse-variance weight to calculate
      fixed- and random-effects summary estimates and corresponding 95% CIs for overall
      and progression-free survival. We did not observe any significant association
      between overall or progression-free survival, neither when considering all
      colorectal cancer patients nor for subgroup analyses (metastatic, anti-EGFR
      [epidermal growth factor receptor] treatment, or KRAS wild type). There was
      substantial heterogeneity across studies, overall and among subgroups analyzed.
      We have found no clear evidence to support an association between the KRAS-LCS6
      genotype and overall or progression-free survival among colorectal cancer
      patients, even after conducting subgroup analyses by stage and anti-EGFR
      treatment status. This information helps to clarify the confusing body of
      literature regarding the clinical implications of the KRAS-LCS6 genetic variant
      on colorectal cancer outcomes, indicating that it should not be used at the
      present time to personalize therapeutic strategies (PROSPERO registration number:
      CRD42013005325). 

PMID- 24890704
TI  - Influence of xylazine on the function of the LiDCO sensor in isoflurane
      anaesthetized horses.
AB  - OBJECTIVE: Previous studies showed an influence of xylazine on the LiDCO sensor
      in vitro and in standing horses, but did not prove that this interaction caused
      error in LiDCO measurements. Therefore, agreement of cardiac output (CO)
      measurements by LiDCO and bolus-thermodilution (BTD) was determined in horses
      receiving xylazine infusions. STUDY DESIGN: Prospective, experimental study.
      ANIMALS: Eight Warmblood horses. METHODS: All horses were premedicated with
      xylazine. Anaesthesia was induced with midazolam and ketamine and was maintained
      with isoflurane in oxygen. During six hours of anaesthesia CO measurements and
      blood samples were taken before, during and after a 60 minute period of xylazine
      infusion. Pairs of LiDCO and bolus thermo-dilution (BTD) measurements of CO were
      performed. Sensor voltages exposed to blood and saline were measured before,
      during and after xylazine infusion and compared using Bland-Altman method of
      agreement with corrections for repeated measures. RESULTS: The CO values (mean +/
      SD) before xylazine were 34.8 +/- 7.3 and 36.4 +/- 8.1 L minute(-1) for BTD and
      LiDCO, respectively. After starting the xylazine infusion, the CO values for BTD
      decreased to 27.5 +/- 6.1 L minute(-1) whereas CO values measured by LiDCO
      increased to 54.7 +/- 18.4 L minute(-1) . One hour after discontinuing xylazine
      infusion, CO values were 33 +/- 6.7 and 36.5 +/-11.9 L minute(-1) for BTD and
      LiDCO, respectively. The difference between saline and blood exposed sensor
      voltages decreased during xylazine infusion and these differences were positive
      numbers before but negative during the infusion. There were correlations between
      xylazine plasma concentrations, CO differences and sensor voltage differences
      (saline - blood). CONCLUSIONS AND CLINICAL RELEVANCE: This study proved that
      xylazine infusion caused concentration dependent bias in LiDCO measurements
      leading to an overestimation of readings. Sensor voltage differences (saline -
      blood) may become valuable clinical tool to predict drug-sensor interactions.

PMID- 24890706
TI  - Design, synthesis, and evaluation of 7H-thiazolo-[3,2-b]-1,2,4-triazin-7-one
      derivatives as dual binding site acetylcholinesterase inhibitors.
AB  - New dual binding site acetylcholinesterase (AChE) inhibitors have been designed
      and synthesized as a new drug candidate for the treatment of Alzheimer's disease
      (AD) through the binding to both catalytic and peripheral sites of the enzyme.
      Therefore, a series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives 6a-j
      were synthesized and investigated for their ability to inhibit the activity of
      human AChE (hAChE) in comparison with huperzine-A. All the compounds were found
      to inhibit AChE activity, especially compounds 6c and 6i with the inhibition
      value of 76.10% and 77.82%, respectively. The molecular docking study indicated
      that they were nicely accommodated by AChE. The molecular docking study revealed
      that 6c and 6i possessed a more optimal binding conformation than 6a and can
      perfectly fit into the active and peripheral site of hAChE, and consequently
      exhibited highly improved inhibitor potency to hAChE. 

PMID- 24890705
TI  - SCAI expert consensus statement for advanced training programs in pediatric and
      congenital interventional cardiac catheterization.
AB  - Pediatric and Congenital Interventional Cardiology is the practice of catheter
      based techniques that improve cardiac physiology and circulation through the
      treatment of heart disease in children and adults with congenital or acquired
      heart defects. Over the last decade, and since last published training guidelines
      for pediatric cardiac catheterization and interventional cardiology were
      published in 2005 [1] the field of Pediatric and Congenital Cardiac
      Catheterization has evolved into a predominantly interventional discipline. As
      there is no sub-specialty certification for interventional cardiac
      catheterization in pediatrics, the Congenital Heart Disease Committee of the
      Society of Cardiovascular Angiography and Interventions has put together this
      consensus statement for advanced training in pediatric and congenital
      interventional cardiac catheterization. The statement puts forth recommendations
      for program infrastructure in terms of teaching, personnel, equipment,
      facilities, conferences, patient volume and trainee assessment. This is meant to
      set a standard for training programs as well as giving applicants a basis on
      which to judge and compare programs.

PMID- 24890707
TI  - Bipolar radiofrequency catheter ablation for refractory ventricular outflow tract
      arrhythmias.
AB  - INTRODUCTION: Standard unipolar radiofrequency ablation (RFA) is typically
      successful in eliminating premature ventricular contractions (PVCs) originating
      from the ventricular outflow tract region. In a minority of cases, this approach
      may be ineffective. We report 4 cases where bipolar RFA was attempted after
      failed unipolar RFA. METHODS: From a total of 73 consecutive PVC ablations, 4
      patients underwent bipolar RFA after failed unipolar ablation. Three-dimensional
      electroanatomic activation mapping of the right and left ventricular outflow
      (RVOT and LVOT), coronary sinus, and aortic root was performed. RESULTS: Mean age
      was 53 +/- 22 years, 3 male. The mean 24-hour PVC burden in these patients was
      33,107 +/- 8,712. In 3 of 4 patients, the RVOT activation was earlier than the
      left side. The earliest activation on the left was in the right coronary cusp in
      2 patients and left coronary cusp in 2. Unipolar RFA delivered sequentially at
      the site of earliest RVOT and then earliest aortic cusp sites failed to eradicate
      the PVCs in all 4 patients. Subsequently, bipolar RFA was applied between
      irrigated catheters placed at the earliest RVOT and aortic root sites. This
      approach eliminated PVCs in 3 of 4 (75%) cases. At a median follow-up of 4
      months, those with successful bipolar RFA had no recurrence of clinical PVCs.
      CONCLUSIONS: This report demonstrates the potential utility of bipolar RFA in
      patients with outflow tract PVCs that fail unipolar RFA.

PMID- 24890709
TI  - Computation of leaky guided waves dispersion spectrum using vibroacoustic
      analyses and the Matrix Pencil Method: a validation study for immersed
      rectangular waveguides.
AB  - The paper aims at validating a recently proposed Semi Analytical Finite Element
      (SAFE) formulation coupled with a 2.5D Boundary Element Method (2.5D BEM) for the
      extraction of dispersion data in immersed waveguides of generic cross-section. To
      this end, three-dimensional vibroacoustic analyses are carried out on two
      waveguides of square and rectangular cross-section immersed in water using the
      commercial Finite Element software Abaqus/Explicit. Real wavenumber and
      attenuation dispersive data are extracted by means of a modified Matrix Pencil
      Method. It is demonstrated that the results obtained using the two techniques are
      in very good agreement. 

PMID- 24890708
TI  - National evaluation of the effectiveness of cognitive behavioral therapy for
      insomnia among older versus younger veterans.
AB  - OBJECTIVES: Limited research has examined the effects of cognitive behavioral
      therapy for insomnia (CBT-I) among older adults (age >65 years) receiving
      treatment in real-world clinical settings and even less has examined effects on
      outcomes beyond reducing insomnia, such as improved quality of life. The current
      article examines and compares outcomes of older versus younger (age 18-64 years)
      veterans receiving CBT-I nationally in nonsleep specialty settings. METHOD:
      Patient outcomes were assessed using the Insomnia Severity Index, Beck Depression
      Inventory-II, and the World Health Organization Quality of Life-BREF. Therapeutic
      alliance was assessed using the Working Alliance Inventory-Short Revised.
      RESULTS: A total of 536 younger veterans and 121 older veterans received CBT-I;
      77% of older and 64% of younger patients completed all sessions or finished early
      due to symptom relief. Mean insomnia scores declined from 19.5 to 9.7 in the
      older group and from 20.9 to 11.1 in the younger group. Within-group effect sizes
      were d = 2.3 and 2.2 for older and younger groups, respectively. CBT-I also
      yielded significant improvements in depression and quality of life for both age
      groups. High and increasing levels of therapeutic alliance were observed for both
      age groups. CONCLUSIONS: Older (and younger) patients receiving CBT-I from
      nonsleep specialists experienced large reductions in insomnia and improvements in
      depression and quality of life. Effects were similar for both age groups, and the
      rate of dropout was lower among older adults. The results provide strong support
      for the effectiveness and acceptability of CBT-I for older adults receiving care
      in routine treatment settings.

PMID- 24890710
TI  - Biological warfare, bioterrorism, and biocrime.
AB  - Biological weapons achieve their intended target effects through the infectivity
      of disease-causing infectious agents. The ability to use biological agents in
      warfare is prohibited by the Biological and Toxin Weapon Convention. Bioterrorism
      is defined as the deliberate release of viruses, bacteria or other agents used to
      cause illness or death in people, but also in animals or plants. It is aimed at
      creating casualties, terror, societal disruption, or economic loss, inspired by
      ideological, religious or political beliefs. The success of bioterroristic
      attempts is defined by the measure of societal disruption and panic, and not
      necessarily by the sheer number of casualties. Thus, making only a few
      individuals ill by the use of crude methods may be sufficient, as long as it
      creates the impact that is aimed for. The assessment of bioterrorism threats and
      motives have been described before. Biocrime implies the use of a biological
      agent to kill or make ill a single individual or small group of individuals,
      motivated by revenge or the desire for monetary gain by extortion, rather than by
      political, ideological, religious or other beliefs. The likelihood of a
      successful bioterrorist attack is not very large, given the technical
      difficulties and constraints. However, even if the number of casualties is likely
      to be limited, the impact of a bioterrorist attack can still be high. Measures
      aimed at enhancing diagnostic and therapeutic capabilities and capacities
      alongside training and education will improve the ability of society to combat
      'regular' infectious diseases outbreaks, as well as mitigating the effects of
      bioterrorist attacks. 

PMID- 24890712
TI  - NEIRD: a neuroendocrine immune network beyond the rheumatic diseases.

PMID- 24890711
TI  - Evaluation of patient preference and willingness to pay for attributes of
      maintenance medication for chronic obstructive pulmonary disease (COPD).
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      morbidity and mortality worldwide. COPD is characterized by poor treatment
      adherence, and patient medication preferences may contribute to adherence.
      METHODS: A discrete choice experiment with an internet panel drawn from the USA
      was used to evaluate preference and willingness to pay (WTP) of COPD patients for
      long-acting maintenance medications. Key attributes derived from earlier
      qualitative research (brief literature review and focus groups) with COPD
      patients on maintenance therapy included symptom relief, speed of feeling
      medication start to work, inhaler ease of use, rescue medication use, side
      effects, and monthly out-of-pocket co-pay. Patients were presented with
      hypothetical medications with different profiles and asked which they preferred.
      Utilities and marginal WTP in monthly co-pay dollars were estimated for all
      patients and by severity. RESULTS: Utilities for 515 participants were in the
      expected direction and highest for the most favorable attribute levels. Each
      attribute evaluated was important, and participants were willing to pay a premium
      to obtain each benefit. On average, WTP was as high as $US64 for complete symptom
      relief, $US59 for no side effects, $US32 to rarely use rescue medication, $US16
      for a quick and easy to use inhaler, and $US13 for feeling medication work
      quickly (within 5 min; average WTP $US18/month for patients with severe/very
      severe COPD). CONCLUSION: As expected, efficacy and safety were most valued by
      patients; however, this study showed that other COPD medication attributes, such
      as rescue medication, ease of use, and feeling medication work quickly, are also
      important in patient preferences.

PMID- 24890713
TI  - Re-interpreting plant morphological responses to UV-B radiation.
AB  - There is a need to reappraise the effects of UV-B radiation on plant morphology
      in light of improved mechanistic understanding of UV-B effects, particularly
      elucidation of the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor. We review
      responses at cell and organismal levels, and explore their underlying regulatory
      mechanisms, function in UV protection and consequences for plant fitness. UV
      induced morphological changes include thicker leaves, shorter petioles, shorter
      stems, increased axillary branching and altered root:shoot ratios. At the
      cellular level, UV-B morphogenesis comprises changes in cell division, elongation
      and/or differentiation. However, notwithstanding substantial new knowledge of
      molecular, cellular and organismal UV-B responses, there remains a clear gap in
      our understanding of the interactions between these organizational levels, and
      how they control plant architecture. Furthermore, despite a broad consensus that
      UV-B induces relatively compact architecture, we note substantial diversity in
      reported phenotypes. This may relate to UV-induced morphological changes being
      underpinned by different mechanisms at high and low UV-B doses. It remains
      unproven whether UV-induced morphological changes have a protective function
      involving shading and decreased leaf penetration of UV-B, counterbalancing trade
      offs such as decreased photosynthetic light capture and plant-competitive
      abilities. Future research will need to disentangle seemingly contradictory
      interactions occurring at the threshold UV dose where regulation and stress
      induced morphogenesis overlap. 

PMID- 24890714
TI  - Modulation enhancement in the electrical signal improves perception of interaural
      time differences with bimodal stimulation.
AB  - Interaural timing cues are important for sound source localization and for
      binaural unmasking of speech that is spatially separated from interfering sounds.
      Users of a cochlear implant (CI) with residual hearing in the non-implanted ear
      (bimodal listeners) can only make very limited use of interaural timing cues with
      their clinical devices. Previous studies showed that bimodal listeners can be
      sensitive to interaural time differences (ITDs) for simple single- and three
      channel stimuli. The modulation enhancement strategy (MEnS) was developed to
      improve the ITD perception of bimodal listeners. It enhances temporal modulations
      on all stimulated electrodes, synchronously with modulations in the acoustic
      signal presented to the non-implanted ear, based on measurement of the amplitude
      peaks occurring at the rate of the fundamental frequency in voiced phonemes. In
      the first experiment, ITD detection thresholds were measured using the method of
      constant stimuli for five bimodal listeners for an artificial vowel, processed
      with either the advanced combination encoder (ACE) strategy or with MEnS. With
      MEnS, detection thresholds were significantly lower, and for four subjects well
      within the physically relevant range. In the second experiment, the extent of
      lateralization was measured in three subjects with both strategies, and ITD
      sensitivity was determined using an adaptive procedure. All subjects could
      lateralize sounds based on ITD and sensitivity was significantly better with MEnS
      than with ACE. The current results indicate that ITD cues can be provided to
      bimodal listeners with modified sound processing. 

PMID- 24890715
TI  - Estimation of neural phase locking from stimulus-evoked potentials.
AB  - The frequency extent over which fine structure is coded in the auditory nerve has
      been physiologically characterized in laboratory animals but is unknown in
      humans. Knowledge of the upper frequency limit in humans would inform the debate
      regarding the role of fine structure in human hearing. Of the presently available
      techniques, only the recording of mass neural potentials offers the promise to
      provide a physiological estimate of neural phase locking in humans. A challenge
      is to disambiguate neural phase locking from the receptor potentials. We studied
      mass potentials recorded on the cochlea and auditory nerve of cat and used
      several experimental manipulations to isolate the neural contribution to these
      potentials. We find a surprisingly large neural contribution in the signal
      recorded on the cochlear round window, and this contribution is in many aspects
      similar to the potential measured on the auditory nerve. The results suggest that
      recording of mass potentials through the middle ear is a promising approach to
      examine neural phase locking in humans. 

PMID- 24890716
TI  - High angular resolution diffusion imaging with stimulated echoes: compensation
      and correction in experiment design and analysis.
AB  - Stimulated echo acquisition mode (STEAM) diffusion MRI can be advantageous over
      pulsed-gradient spin-echo (PGSE) for diffusion times that are long compared with
      T2 . It therefore has potential for biomedical diffusion imaging applications at
      7T and above where T2 is short. However, gradient pulses other than the diffusion
      gradients in the STEAM sequence contribute much greater diffusion weighting than
      in PGSE and lead to a disrupted experimental design. Here, we introduce a simple
      compensation to the STEAM acquisition that avoids the orientational bias and
      disrupted experiment design that these gradient pulses can otherwise produce. The
      compensation is simple to implement by adjusting the gradient vectors in the
      diffusion pulses of the STEAM sequence, so that the net effective gradient vector
      including contributions from diffusion and other gradient pulses is as the
      experiment intends. High angular resolution diffusion imaging (HARDI) data were
      acquired with and without the proposed compensation. The data were processed to
      derive standard diffusion tensor imaging (DTI) maps, which highlight the need for
      the compensation. Ignoring the other gradient pulses, a bias in DTI parameters
      from STEAM acquisition is found, due both to confounds in the analysis and the
      experiment design. Retrospectively correcting the analysis with a calculation of
      the full B matrix can partly correct for these confounds, but an acquisition that
      is compensated as proposed is needed to remove the effect entirely.

PMID- 24890717
TI  - Characterization of conventional and atypical receptors for the chemokine CCL2 on
      mouse leukocytes.
AB  - Chemokine-directed leukocyte migration is crucial for effective immune and
      inflammatory responses. Conventional chemokine receptors (cCKRs) directly control
      cell movement; atypical chemokine receptors (ACKRs) regulate coexpressed cCKRs;
      and both cCKRs and ACKRs internalize chemokines to limit their abundance in vivo,
      a process referred to as scavenging. A leukocyte's migratory and chemokine
      scavenging potential is determined by which cCKRs and ACKRs it expresses, and by
      the ligand specificity, signaling properties, and chemokine internalization
      capacity of these receptors. Most chemokines can bind at least one cCKR and one
      ACKR. CCL2 can bind to CCR2 (a cCKR) and two ACKRs (ACKR1 and ACKR2). In this
      study, by using fluorescent CCL2 uptake to label cells bearing functional CCL2
      receptors, we have defined the expression profile, scavenging activity, and
      ligand specificity of CCL2 receptors on mouse leukocytes. We show that
      qualitative and quantitative differences in the expression of CCR2 and ACKR2
      endow individual leukocyte subsets with distinctive CCL2 receptor profiles and
      CCL2-scavenging capacities. We reveal that some cells, including plasmacytoid
      dendritic cells, can express both CCR2 and ACKR2; that Ly6C(high) monocytes have
      particularly strong CCL2-scavenging potential in vitro and in vivo; and that CCR2
      is a much more effective CCL2 scavenger than ACKR2. We confirm the unique,
      overlapping, ligand specificities of CCR2 and ACKR2 and, unexpectedly, find that
      cell context influences the interaction of CCL7 and CCL12 with CCR2. Fluorescent
      chemokine uptake assays were instrumental in providing these novel insights into
      CCL2 receptor biology, and the sensitivity, specificity, and versatility of these
      assays are discussed. 

PMID- 24890718
TI  - Accumulation of serial forces on TCR and CD8 frequently applied by agonist
      antigenic peptides embedded in MHC molecules triggers calcium in T cells.
AB  - T cell activation by Ag is one of the key events in adaptive immunity. It is
      triggered by interactions of the TCR and coreceptor (CD8 or CD4) with antigenic
      peptides embedded in MHC (pMHC) molecules expressed on APCs. The mechanism of how
      signal is initiated remains unclear. In this article, we complement our two
      dimensional kinetic analysis of TCR-pMHC-CD8 interaction with concurrent calcium
      imaging to examine how ligand engagement of TCR with and without the coengagement
      of CD8 initiates signaling. We found that accumulation of frequently applied
      forces on the TCR via agonist pMHC triggered calcium, which was further enhanced
      by CD8 cooperative binding. Prolonging the intermission between sequential force
      applications impaired calcium signals. Our data support a model where rapid
      accumulation of serial forces on TCR-pMHC-CD8 bonds triggers calcium in T cells. 

PMID- 24890719
TI  - T cell activation regulates CD6 alternative splicing by transcription dynamics
      and SRSF1.
AB  - The T cell-surface glycoprotein CD6 is a modulator of cellular responses and has
      been implicated in several autoimmune diseases such as multiple sclerosis,
      rheumatoid arthritis, and psoriasis. During Ag presentation, CD6 is targeted to
      the immunological synapse in a ligand binding-dependent manner, in which CD6
      domain 3 directly contacts CD166, expressed on the APC. T cell activation results
      in the induction of CD6Deltad3, an alternatively spliced isoform that lacks the
      ligand-binding domain and thus no longer localizes at the immunological synapse.
      In this study, we investigated the molecular mechanisms regulating the expression
      of CD6Deltad3 upon human primary T cell activation. Using chromatin
      immunoprecipitation, we observed an increase in RNA polymerase II occupancy along
      the CD6 gene and augmented CD6 transcription. We showed that activation leads to
      transcription-related chromatin modifications, revealed by higher CD6 acetylation
      levels. Modulation of chromatin conformation using a histone deacetylase
      inhibitor that increases transcription rate causes an increase of exon 5
      skipping. We further showed that the splicing factor SRSF1 binds to a regulatory
      element in CD6 intron 4, activating exon 5 splicing and promoting exon 5
      inclusion. Concomitant with T cell activation-induced exon 5 skipping, we
      observed a downregulation of SRSF1. Using RNA immunoprecipitation, we showed that
      in activated T cells, SRSF1 recruitment to the CD6 transcript is impaired by
      increased chromatin acetylation levels. We propose that upon T cell activation,
      SRSF1 becomes limiting, and its function in CD6 exon 5 splicing is countered by
      an increase in CD6 transcription, dependent on chromatin acetylation. 

PMID- 24890720
TI  - Aspirin activation of eosinophils and mast cells: implications in the
      pathogenesis of aspirin-exacerbated respiratory disease.
AB  - Reactions to aspirin and nonsteroidal anti-inflammatory drugs in patients with
      aspirin-exacerbated respiratory disease (AERD) are triggered when constraints
      upon activated eosinophils, normally supplied by PGE2, are removed secondary to
      cyclooxygenase-1 inhibition. However, the mechanism driving the concomitant
      cellular activation is unknown. We investigated the capacity of aspirin itself to
      provide this activation signal. Eosinophils were enriched from peripheral blood
      samples and activated with lysine ASA (LysASA). Parallel samples were stimulated
      with related nonsteroidal anti-inflammatory drugs. Activation was evaluated as
      Ca2+ flux, secretion of cysteinyl leukotrienes (CysLT), and eosinophil-derived
      neurotoxin (EDN) release. CD34+ progenitor-derived mast cells were also used to
      test the influence of aspirin on human mast cells with measurements of Ca2+ flux
      and PGD2 release. LysASA induced Ca2+ fluxes and EDN release, but not CysLT
      secretion from circulating eosinophils. There was no difference in the
      sensitivity or extent of activation between AERD and control subjects, and sodium
      salicylate was without effect. Like eosinophils, aspirin was able to activate
      human mast cells directly through Ca2+ flux and PGD2 release. AERD is associated
      with eosinophils maturing locally in a high IFN-gamma milieu. As such, in
      additional studies, eosinophil progenitors were differentiated in the presence of
      IFN-gamma prior to activation with aspirin. Eosinophils matured in the presence
      of IFN-gamma displayed robust secretion of both EDN and CysLTs. These studies
      identify aspirin as the trigger of eosinophil and mast cell activation in AERD,
      acting in synergy with its ability to release cells from the anti-inflammatory
      constraints of PGE2.

PMID- 24890723
TI  - Infiltrating monocyte-derived macrophages and resident kupffer cells display
      different ontogeny and functions in acute liver injury.
AB  - The liver has a remarkable capacity to regenerate after injury; yet, the role of
      macrophages (MF) in this process remains controversial mainly due to difficulties
      in distinguishing between different MF subsets. In this study, we used a murine
      model of acute liver injury induced by overdose of N-acetyl-p-aminophenol (APAP)
      and defined three distinct MF subsets that populate the liver following injury.
      Accordingly, resident Kupffer cells (KC) were significantly reduced upon APAP
      challenge and started recovering by self-renewal at resolution phase without
      contribution of circulating Ly6C(hi) monocytes. The latter were recruited in a
      CCR2- and M-CSF-mediated pathway at the necroinflammatory phase and
      differentiated into ephemeral Ly6C(lo) MF subset at resolution phase. Moreover,
      their inducible ablation resulted in impaired recovery. Microarray-based
      molecular profiling uncovered high similarity between steady-state KC and those
      recovered at the resolution phase. In contrast, KC and monocyte-derived MF
      displayed distinct prorestorative genetic signature at the resolution phase.
      Finally, we show that infiltrating monocytes acquire a prorestorative
      polarization manifested by unique expression of proangiogenesis mediators and
      genes involved with inhibition of neutrophil activity and recruitment and
      promotion of their clearance. Collectively, our results present a novel
      phenotypic, ontogenic, and molecular definition of liver-MF compartment following
      acute injury. 

PMID- 24890722
TI  - Cutting edge: Antigen-specific thymocyte feedback regulates homeostatic thymic
      conventional dendritic cell maturation.
AB  - Thymic dendritic cells (DC) mediate self-tolerance by presenting self-peptides to
      and depleting autoreactive thymocytes. Despite a significant role in negative
      selection, the events regulating thymic DC maturation and function under steady
      state conditions are poorly understood. We report that cross-talk with thymocytes
      regulates thymic conventional DC (cDC) numbers, phenotype, and function. In mice
      lacking TCR-expressing thymocytes, thymic cDC were reduced and exhibited a less
      mature phenotype. Furthermore, thymic cDC in TCR-transgenic mice lacking cognate
      Ag expression in the thymus were also immature; notably, however, thymic cDC
      maturation was re-established by an Ag-specific cognate interaction with CD4+ or
      CD8+ single-positive thymocytes (SP). Blockade of CD40L during Ag-specific
      interactions with CD4 SP, but not CD8 SP, limited the effect on cDC maturation.
      Together, these novel findings demonstrate that homeostatic maturation and
      function of thymic cDC are regulated by feedback delivered by CD4 SP and CD8 SP
      via distinct mechanisms during a cognate Ag-specific interaction.

PMID- 24890721
TI  - Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and
      antibody response.
AB  - Lysophospholipids have emerged as biologically important chemoattractants capable
      of directing lymphocyte development, trafficking, and localization.
      Lysophosphatidic acid (LPA) is a major lysophospholipid found systemically, and
      its levels are elevated in certain pathological settings, such as cancer and
      infections. In this study, we demonstrate that BCR signal transduction by mature
      murine B cells is inhibited upon LPA engagement of the LPA5 (GPR92) receptor via
      a Galpha12/13-Arhgef1 pathway. The inhibition of BCR signaling by LPA5 manifests
      by impaired intracellular calcium store release and most likely by interfering
      with inositol 1,4,5-triphosphate receptor activity. We further show that LPA5
      also limits Ag-specific induction of CD69 and CD86 expression and that LPA5
      deficient B cells display enhanced Ab responses. Thus, these data show that LPA5
      negatively regulates BCR signaling, B cell activation, and immune response. Our
      findings extend the influence of lysophospholipids on immune function and suggest
      that alterations in LPA levels likely influence adaptive humoral immunity. 

PMID- 24890724
TI  - Bovine gammadelta T cells are a major regulatory T cell subset.
AB  - In humans and mice, gammadelta T cells represent <5% of the total circulating
      lymphocytes. In contrast, the gammadelta T cell compartment in ruminants accounts
      for 15-60% of the total circulating mononuclear lymphocytes. Despite the
      existence of CD4(+)CD25(high) Foxp3(+) T cells in the bovine system, these are
      neither anergic nor suppressive. We present evidence showing that bovine
      gammadelta T cells are the major regulatory T cell subset in peripheral blood.
      These gammadelta T cells spontaneously secrete IL-10 and proliferate in response
      to IL-10, TGF-beta, and contact with APCs. IL-10-expressing gammadelta T cells
      inhibit Ag-specific and nonspecific proliferation of CD4(+) and CD8(+) T cells in
      vitro. APC subsets expressing IL-10 and TFG-beta regulate proliferation of
      gammadelta T cells producing IL-10. We propose that gammadelta T cells are a
      major regulatory T cell population in the bovine system. 

PMID- 24890726
TI  - Cutting edge: Parathyroid hormone facilitates macrophage efferocytosis in bone
      marrow via proresolving mediators resolvin D1 and resolvin D2.
AB  - Bone marrow macrophages stimulate skeletal wound repair and osteoblastic bone
      formation by poorly defined mechanisms. Specialized proresolving mediators of
      inflammation drive macrophage efferocytosis (phagocytosis of apoptotic cells) and
      resolution, but little is known regarding this process in the bone marrow. In
      this study, metabololipidomic profiling via liquid chromatography mass
      spectrometry revealed higher levels of specialized proresolving mediators in the
      bone marrow relative to the spleen. The endocrine and bone anabolic agent
      parathyroid hormone increased specialized proresolving mediator levels, including
      resolvins (Rvs), in bone marrow. Human and murine primary macrophages
      efferocytosed apoptotic osteoblasts in vitro, and RvD1 and RvD2 (10 pM-10 nM)
      enhanced this process. These findings support a unique profile of specialized
      lipid mediators in bone marrow that contribute to a feedback system for
      resolution of inflammation and maintenance of skeletal homeostasis. 

PMID- 24890725
TI  - IL-27 limits central nervous system viral clearance by promoting IL-10 and
      enhances demyelination.
AB  - IL-27 is a pleiotropic member of the IL-6 and IL-12 cytokine family composed of
      the IL-27p28 and the EBV-induced gene 3. IL-27 and its receptor mRNA are both
      upregulated in the CNS during acute encephalomyelitis induced by the JHM strain
      of mouse hepatitis virus (JHMV) and sustained during viral persistence.
      Contributions of IL-27 to viral pathogenesis were evaluated by infection of IL
      27Ralpha-chain-deficient (IL-27Ralpha(-/-)) mice. The absence of IL-27 signaling
      accelerated virus control within the CNS associated with increased IFN-gamma
      secreting virus-specific CD4+ and CD8+ T cells. Abrogation of IL-27 signaling did
      not affect virus-specific CD8+ T cell-mediated IL-10 production or cytolytic
      activity or Foxp3+ regulatory T cell populations. However, IL-10 production by
      virus-specific CD4+ T cells was reduced significantly. Despite increased T cell
      mediated antiviral function in IL-27Ralpha(-/-) mice, the virus persisted in the
      CNS at similar levels as in wild-type mice. Nevertheless, IL-27Ralpha(-/-) mice
      exhibited decreased clinical disease during persistence, coincident with less
      severe demyelination, the hallmark tissue damage associated with JHMV infection.
      Overall, these data demonstrate that in contrast to viral infections at other
      sites, IL-27 does not play a proinflammatory role during JHMV-induced
      encephalomyelitis. Rather, it limits CNS inflammation and impairs control of CNS
      virus replication via induction of IL-10 in virus-specific CD4+ T cells.
      Furthermore, in contrast to its protective role in limiting CNS autoimmunity and
      preventing immunopathology, these data define a detrimental role of IL-27 in
      promoting demyelination by delaying viral control.

PMID- 24890728
TI  - Gcsf-Chr19 promotes neutrophil migration to damaged tissue through blood vessels
      in zebrafish.
AB  - G-CSF is an essential cytokine that regulates proliferation and differentiation
      of granulocytes from hematopoietic stem and progenitor cells. In mammals G-CSF
      has been identified as a key factor that promotes the release of neutrophils from
      the bone marrow into the blood circulation. In silico analysis indicates that
      zebrafish has two gcsf genes, gcsf-chr12 in chromosome 12 and gcsf-chr19 in
      chromosome 19. Gcsf-Chr12 participates in emergency myelopoiesis, but, in
      contrast to its mammalian orthologue, is not involved in neutrophil migration
      toward damaged tissue. In turn, the function of Gcsf-Chr19 has not been examined
      yet. In this study, we analyzed the role of Gcsf-Chr19 in regulating neutrophil
      migration toward the wound. Our results indicated that during the first h after
      caudal fin transection, neutrophils migrate from the hematopoietic tissue toward
      the injury, using the extracellular matrix as a substrate. Later, between 3 and 4
      h postdamage, the recruitment mainly occurs through the bloodstream, and only a
      few neutrophils still use the extracellular matrix to migrate. During this
      process, the transcriptional levels of gcsf-chr19 are considerably increased,
      reaching a peak 1 h postdamage. The knockdown of Gcsf-chr19 indicated that the
      percentage of neutrophils that reach the wound decreased after the first h
      postinjury, suggesting that the knockdown specifically affects neutrophils that
      travel to the wound through blood vessels. Together, our data provide novel
      information about the regulation of neutrophil migration in zebrafish,
      positioning Gcsf-Chr19 as a key signal during the course of an inflammatory
      process triggered by severe damage. 

PMID- 24890727
TI  - Tofacitinib suppresses antibody responses to protein therapeutics in murine
      hosts.
AB  - Immunogenicity remains the "Achilles' heel" of protein-based therapeutics. Anti
      drug Abs produced in response to protein therapeutics can severely limit both the
      safety and efficacy of this expanding class of agent. In this article, we report
      that monotherapy of mice with tofacitinib (the JAK inhibitor) quells Ab responses
      to an immunotoxin derived from the bacterial protein Pseudomonas exotoxin A, as
      well as to the model Ag keyhole limpet hemocyanin. Thousand-fold reductions in
      IgG1 titers to both Ags were observed 21 d post immunization. In fact,
      suppression was evident for all IgG isotypes and IgM. A reduction in IgG3
      production was also noted with a thymus-independent type II Ag. Mechanistic
      investigations revealed that tofacitinib treatment led to reduced numbers of
      CD127+ pro-B cells. Furthermore, we observed fewer germinal center B cells and
      the impaired formation of germinal centers of mice treated with tofacitinib.
      Because normal Ig levels were still present during tofacitinib treatment, this
      agent specifically reduced anti-drug Abs, thus preserving the potential efficacy
      of biological therapeutics, including those used as cancer therapeutics.

PMID- 24890730
TI  - Neuropsychological functioning of children treated for acute lymphoblastic
      leukemia: impact of whole brain radiation therapy.
AB  - OBJECTIVES: To provide one of the first prospective reports examining
      neuropsychological outcomes for children treated with 1800 cGy whole brain
      radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic
      chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term
      neuropsychological toxicities associated with WBRT are compared. METHODS: This
      multisite study included 188 children, ages 4-21 years at enrollment, who were
      assessed with standardized neuropsychological tests at 9, 21, and 48 months after
      diagnosis with intermediate risk ALL. All participating children were receiving
      treatment on a parent study CCG105. RESULTS: Verbal intelligence (VIQ) scores for
      children receiving WBRT was significantly lower than VIQ for prophylactic
      chemotherapy at the 48-month time point (p < 0.05). A significant cross-level
      interaction between time since diagnosis and treatment condition was observed (p
      < 0.05). WBRT did not result in differences in PIQ; both groups of children
      demonstrated comparable increases in PIQ. Neuropsychological findings at 48
      months after diagnosis indicated diminished performance in neuromotor, visual
      motor coordination, and executive functioning for children receiving WBRT.
      Academic achievement was unaffected by WBRT at 4 years after diagnosis.
      CONCLUSIONS: The measurement of verbal and performance IQ as a primary endpoint
      in ALL clinical trials is critical to characterizing neuropsychological late
      effects. A trajectory of decline in neuropsychological functioning, specifically
      verbal IQ, was observed. Missing data within the trial occurred at random and did
      not impact results observed. The impact of WBRT becomes evident at 48 months
      after diagnosis, suggesting the need for long-term follow-up beyond the time
      frame typically used in Phase III trials.

PMID- 24890729
TI  - IL-1beta promotes the differentiation of polyfunctional human CCR6+CXCR3+ Th1/17
      cells that are specific for pathogenic and commensal microbes.
AB  - In humans, Th1/17 cells, identified by coexpression of the chemokine receptors
      CCR6 and CXCR3, are proposed to be highly pathogenic in several autoimmune
      disorders due in part to their expression of the proinflammatory cytokines IL-17,
      IFN-gamma, and GM-CSF. However, their developmental requirements, relationship
      with "classic" Th17 and Th1 cells and physiological role in normal immune
      responses are not well understood. In this study, we examined CCR6+ CXCR3+ Th1/17
      cells from healthy individuals and found that ex vivo these cells produced the
      effector cytokines IL-17, IL-22, and IFN-gamma in all possible combinations and
      were highly responsive to both IL-12 and IL-23. Moreover, although the Ag
      specificity of CCR6+ CXCR3+ Th1/17 cells showed substantial overlap with that of
      Th1 and Th17 cells, this population was enriched in cells recognizing certain
      extracellular bacteria and expressing the intestinal homing receptor integrin
      beta7. Finally, we identified IL-1beta as a key cytokine that renders Th17 cells
      sensitive to IL-12, and both cytokines together potently induced the
      differentiation of cells that produce IL-17, IFN-gamma, and GM-CSF. Therefore,
      interfering with IL-1beta and IL-12 signaling in Th17 cells during inflammation
      may be a promising therapeutic approach to reduce their differentiation into
      "pathogenic" CCR6+ CXCR3+ Th1/17 cells in patients with autoimmune diseases.

PMID- 24890731
TI  - Pilot Test of a Preconception and Midwifery Care Promotion Program for College
      Women.
AB  - INTRODUCTION: College campuses remain an underused setting for implementing the
      10 strategies for promoting preconception health proposed by the US Centers for
      Disease Control and Prevention. This setting can also be used to educate young
      women about their options for care in future pregnancies, including midwifery
      care. To address these needs, the author and 2 peer educators developed and pilot
      tested a multiweek health education program for college women. METHODS: Women
      from a small public liberal arts college in the mid-Atlantic region of the United
      States were recruited to participate in the pilot program, which offered 6 hours
      of education over 4 weeks in an interactive, participant-led format. Of 26 women
      who participated, 20 completed at least 3 of the 4 sessions, as well as the pre-
      and posttests. RESULTS: The program group reported greater awareness of the
      importance of preconception health and an increased preference for midwifery care
      in future pregnancies. Program participants experienced an increase in knowledge
      about preconception health, midwifery care, and risks associated with cesarean
      birth, labor induction, and preterm birth, but did not report a statistically
      significant change in behavior related to preconception health, including
      lifestyle changes and immunizations. DISCUSSION: Further research should be
      conducted with a larger sample, longer follow-up, and a more rigorous evaluation
      design to assess the potential contributions of this promising pilot program.

PMID- 24890732
TI  - Additional value of fetal magnetic resonance imaging in the prenatal diagnosis of
      central nervous system anomalies: a systematic review of the literature.
AB  - OBJECTIVES: To analyze literature on the additional value of fetal magnetic
      resonance imaging (MRI) in assessing central nervous system (CNS) anomalies
      suspected by ultrasound. METHODS: A search was performed of PubMed, EMBASE,
      Cochrane library and the reference lists of identified articles. Inclusion
      criteria were CNS anomalies suspected/diagnosed by ultrasound, MRI performed
      after ultrasound, and postmortem examination by autopsy or postnatal assessment.
      MOOSE guidelines were followed. Outcomes assessed were positive/negative
      agreement between ultrasound and MRI, additional information provided by MRI, and
      discordance between ultrasound and MRI. Pooled sensitivity and specificity of MRI
      were calculated using the DerSimonian-Laird method. Postnatal/postmortem
      examinations were used as the reference standard. RESULTS: We identified thirteen
      articles which included 710 fetuses undergoing both ultrasound and MRI. MRI
      confirmed ultrasound-positive findings in 65.4% of fetuses and provided
      additional information in 22.1%. MRI disclosed CNS anomalies in 18.4% of fetuses.
      In 2.0% of cases, ultrasound was more accurate than MRI. In 30% of fetuses, MRI
      was so different from ultrasound that the clinical management changed. Agreement
      was observed mainly for ventriculomegaly (51.3%). Disagreement was noted mainly
      for midline anomalies (48.6%). Pooled sensitivity of MRI was 97% (95% CI, 95-98%)
      and pooled specificity was 70% (95% CI, 58-81%). CONCLUSIONS: MRI supplements the
      information provided by ultrasound. It should be considered in selected fetuses
      with CNS anomalies suspected on ultrasound.

PMID- 24890733
TI  - Mutation update and uncommon phenotypes in a French cohort of 96 patients with
      WFS1-related disorders.
AB  - WFS1 mutations are responsible for Wolfram syndrome (WS) characterized by
      juvenile-onset diabetes mellitus and optic atrophy, and for low-frequency
      sensorineural hearing loss (LFSNHL). Our aim was to analyze the French cohort of
      96 patients with WFS1-related disorders in order (i) to update clinical and
      molecular data with 37 novel affected individuals, (ii) to describe uncommon
      phenotypes and, (iii) to precise the frequency of large-scale rearrangements in
      WFS1. We performed quantitative polymerase chain reaction (PCR) in 13 patients,
      carrying only one heterozygous variant, to identify large-scale rearrangements in
      WFS1. Among the 37 novel patients, 15 carried 15 novel deleterious putative
      mutations, including one large deletion of 17,444 base pairs. The analysis of the
      cohort revealed unexpected phenotypes including (i) late-onset symptoms in 13.8%
      of patients with a probable autosomal recessive transmission; (ii) two siblings
      with recessive optic atrophy without diabetes mellitus and, (iii) six patients
      from four families with dominantly-inherited deafness and optic atrophy. We
      highlight the expanding spectrum of WFS1-related disorders and we show that, even
      if large deletions are rare events, they have to be searched in patients with
      classical WS carrying only one WFS1 mutation after sequencing. 

PMID- 24890734
TI  - Long-term effects of stock transfers: synergistic introgression of allochthonous
      genomes in salmonids.
AB  - The genus Salmo was employed as a model to study introgression of genes between
      species due to secondary contacts. Seven microsatellite loci, the LDH-C1* locus
      and the 5S ribosomal DNA were studied. Results showed the mutually enhanced
      introgression of allochthonous genomes into southern European salmonids. This
      phenomenon appears to go beyond a simple consequence of the altered behaviour of
      domestic individuals. Invasions of autochthonous genomes by allochthonous genes
      would be enhanced by human activities such as stock transfers, which would
      simultaneously promote allochthonous and allospecific (from other species)
      introgressions in a synergistic process in Atlantic salmon Salmo salar and brown
      trout Salmo trutta. As a minor result, the data do not support the value of the
      microsatellite locus SsaD486 as a species-specific marker. 

PMID- 24890735
TI  - Finite difference approximations for a size-structured population model with
      distributed states in the recruitment.
AB  - We consider a size-structured population model where individuals may be recruited
      into the population at different sizes. First- and second-order finite difference
      schemes are developed to approximate the solution of the model. The convergence
      of the approximations to a unique weak solution is proved. We then show that as
      the distribution of the new recruits become concentrated at the smallest size,
      the weak solution of the distributed states-at-birth model converges to the weak
      solution of the classical Gurtin-McCamy-type size-structured model in the weak*
      topology. Numerical simulations are provided to demonstrate the achievement of
      the desired accuracy of the two methods for smooth solutions as well as the
      superior performance of the second-order method in resolving solution
      discontinuities. Finally, we provide an example where supercritical Hopf
      bifurcation occurs in the limiting single state-at-birth model and we apply the
      second-order numerical scheme to show that such bifurcation also occurs in the
      distributed model. 

PMID- 24890736
TI  - Molecular characterization of a naturally occurring intraspecific recombinant
      begomovirus with close relatives widespread in southern Arabia.
AB  - BACKGROUND: Tomato leaf curl Sudan virus (ToLCSDV) is a single-stranded DNA
      begomovirus of tomato that causes downward leaf curl, yellowing, and stunting.
      Leaf curl disease results in significant yield reduction in tomato crops in the
      Nile Basin. ToLCSDV symptoms resemble those caused by Tomato yellow leaf curl
      virus, a distinct and widespread begomovirus originating in the Middle East. In
      this study, tomato samples exhibiting leaf curl symptoms were collected from
      Gezira, Sudan. The associated viral genome was molecularly characterized,
      analyzed phylogenetically, and an infectious clone for one isolate was
      constructed. FINDINGS: The complete genomes for five newly discovered variants of
      ToLCSDV, ranging in size from 2765 to 2767-bp, were cloned and sequenced, and
      subjected to pairwise and phylogenetic analyses. Pairwise analysis indicated that
      the five Gezira isolates shared 97-100% nucleotide identity with each other.
      Further, these variants of ToLCSDV shared their highest nucleotide identity at 96
      98%, 91-95%, 91-92%, and 91-92% with the Shambat, Gezira, Oman and Yemen strains
      of ToLCSDV, respectively. Based on the high maximum nucleotide identities shared
      between these ToLCSDV variants from Gezira and other previously recognized
      members of this taxonomic group, they are considered isolates of the Shambat
      strain of ToLCSDV. Analysis of the complete genome sequence for these new
      variants revealed that they were naturally occurring recombinants between two
      previously reported strains of ToLCSDV. Finally, a dimeric clone constructed from
      one representative ToLCSV genome from Gezira was shown to be infectious following
      inoculation to tomato and N. benthamiana plants. CONCLUSION: Five new, naturally
      occurring recombinant begomovirus variants (>96% shared nt identity) were
      identified in tomato plants from Gezira in Sudan, and shown to be isolates of the
      Shambat strain of ToLCSDV. The cloned viral genome was infectious in N.
      benthamiana and tomato plants, and symptoms in tomato closely resembled those
      observed in field infected tomato plants, indicating the virus is the causal
      agent of the leaf curl disease. The symptoms that developed in tomato seedlings
      closely resembled those observed in field infected tomato plants, indicating that
      ToLCSDV is the causal agent of the leaf curl disease in Gezira.

PMID- 24890737
TI  - The role of immigration and local adaptation on fine-scale genotypic and
      phenotypic population divergence in a less mobile passerine.
AB  - Dispersal and local patterns of adaptation play a major role on the ecological
      and evolutionary trajectory of natural populations. In this study, we employ a
      combination of genetic (25 microsatellite markers) and field-based information
      (seven study years) to analyse the impact of immigration and local patterns of
      adaptation in two nearby (<7 km) blue tit (Cyanistes caeruleus) populations. We
      used genetic assignment analyses to identify immigrant individuals and found that
      dispersal rate is female-biased (72%). Data on lifetime reproductive success
      indicated that immigrant females produced fewer local recruits than their
      philopatric counterparts whereas immigrant males recruited more offspring than
      those that remained in their natal location. In spite of the considerably higher
      immigration rates of females, our results indicate that, in absolute terms, their
      demographic and genetic impact in the receiving populations is lower than that in
      immigrant males. Immigrants often brought novel alleles into the studied
      populations and a high proportion of them were transmitted to their recruits,
      indicating that the genetic impact of immigrants is not ephemeral. Although only
      a few kilometres apart, the two study populations were genetically differentiated
      and showed strong divergence in different phenotypic and life-history traits. An
      almost absent inter-population dispersal, together with the fact that both
      populations receive immigrants from different source populations, is probably the
      main cause of the observed pattern of genetic differentiation. However,
      phenotypic differentiation (PST) for all the studied traits greatly exceeded
      neutral genetic differentiation (FST), indicating that divergent natural
      selection is the prevailing factor determining the evolutionary trajectory of
      these populations. Our study highlights the importance of integrating individual-
      and population-based approaches to obtain a comprehensive view about the role of
      dispersal and natural selection on structuring the genotypic and phenotypic
      characteristics of natural populations.

PMID- 24890739
TI  - A 3D aluminoborate open framework interpenetrated by 2D zinc-amine coordination
      polymer networks in its 11-ring channels.
AB  - A new inorganic-organic hybrid solid, [Zn(dap)2 ][AlB5 O10 ], combining the
      structural features of 3D open-framework inorganic solids and 2D metal-organic
      coordination polymers has been synthesized under solvothermal conditions. The
      compound displays extensive luminescence and moderate second-harmonic-generation
      efficiency. 

PMID- 24890738
TI  - Tiotropium Respimat(r) in asthma: a double-blind, randomised, dose-ranging study
      in adult patients with moderate asthma.
AB  - BACKGROUND: Tiotropium, a once-daily long-acting anticholinergic bronchodilator,
      when administered via Respimat(r) SoftMistTM inhaler (tiotropium Respimat(r))
      significantly reduces the risk of severe exacerbations and improves lung function
      in patients with severe persistent asthma that is not fully controlled despite
      using inhaled corticosteroids (ICS) and long-acting beta2-agonists. To further
      explore the dose-response curve in asthma, we investigated the efficacy and
      safety of three different doses of tiotropium Respimat(r) as add-on to ICS in
      symptomatic patients with moderate persistent asthma. METHODS: In this
      randomised, double-blind, placebo-controlled, four-way crossover study, patients
      were randomised to tiotropium Respimat(r) 5 MUg, 2.5 MUg or 1.25 MUg or placebo
      Respimat(r), once daily in the evening. Each treatment was administered for 4
      weeks, without washout between treatment periods. Eligibility criteria included
      >=60% and <=90% of predicted normal forced expiratory volume in 1 second (FEV1)
      and seven-question Asthma Control Questionnaire mean score of >=1.5. Patients
      were required to continue maintenance treatment with stable medium-dose ICS for
      at least 4 weeks prior to and during the treatment period. Long-acting beta2
      agonists were not permitted during the treatment phase. The primary efficacy end
      point was peak FEV1 measured within 3 hours after dosing (peak FEV1(0-3h)) at the
      end of each 4-week period, analysed as a response (change from study baseline).
      RESULTS: In total, 149 patients were randomised and 141 completed the study.
      Statistically significant improvements in peak FEV1(0-3h) response were observed
      with each tiotropium Respimat(r) dose versus placebo (all P < 0.0001). The
      largest difference from placebo was with tiotropium Respimat(r) 5 MUg (188 mL).
      Trough FEV1 and FEV1 area under the curve (AUC)(0-3h) responses were greater with
      each tiotropium Respimat(r) dose than with placebo (all P < 0.0001), and both
      were greatest with 5 MUg. Peak forced vital capacity (FVC)(0-3h), trough FVC and
      FVC AUC(0-3h) responses, versus placebo, were greatest with tiotropium
      Respimat(r) 5 MUg (P < 0.0001, P = 0.0012 and P < 0.0001, respectively).
      Incidence of adverse events was comparable between placebo and all tiotropium
      Respimat(r) groups. CONCLUSIONS: Once-daily tiotropium Respimat(r) add-on to
      medium-dose ICS improves lung function in symptomatic patients with moderate
      asthma. Overall, improvements were largest with tiotropium Respimat(r) 5 MUg.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01233284.

PMID- 24890741
TI  - The effect of equipment proximity on safe performance in a manufacturing setting.
AB  - We examined the effect of equipment proximity on the safe performance of 3
      assembly workers in a manufacturing setting. After a baseline period in which
      protective eyewear was kept 6.1 m from employee workstations, task clarification
      was used to inform participants to wear their eyewear while they worked. Next,
      the eyewear was moved to 1.5 m from employee workstations. After a return to the
      6.1-m condition, the eyewear was again positioned 1.5 m from workstations.
      Results indicate that task clarification alone was ineffective, but safe
      performance increased when eyewear was stored in close proximity to employees. A
      social validity measure suggested that safe performance among the employees
      increased to levels comparable to that of an exemplary employee.

PMID- 24890742
TI  - Abortion law reform in Nepal.
AB  - Across four decades of political and social action, Nepal changed from a country
      strongly enforcing oppressive abortion restrictions, causing many poor women's
      long imprisonment and high rates of abortion-related maternal mortality, into a
      modern democracy with a liberal abortion law. The medical and public health
      communities supported women's rights activists in invoking legal principles of
      equality and non-discrimination as a basis for change. Legislative reform of the
      criminal ban in 2002 and the adoption of an Interim Constitution recognizing
      women's reproductive rights as fundamental rights in 2007 inspired the Supreme
      Court in 2009 to rule that denial of women's access to abortion services because
      of poverty violated their constitutional rights. The government must now provide
      services under criteria for access without charge, and services must be
      decentralized to promote equitable access. A strong legal foundation now exists
      for progress in social justice to broaden abortion access and reduce abortion
      stigma. 

PMID- 24890740
TI  - Immune and anticancer responses elicited by fully synthetic aberrantly
      glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist.
AB  - The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial
      cancer cells manifested by truncated O-linked saccharides. Although tumor
      associated MUC1 has generated considerable attention because of its potential for
      the development of a therapeutic cancer vaccine, it has been difficult to design
      constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC
      mediating antibodies specific for the tumor form of MUC1. We have designed,
      chemically synthesized, and immunologically examined vaccine candidates each
      composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and
      a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist. It was found that the Pam3
      CysSK4 -containing compound elicits more potent antigenic and cellular immune
      responses, resulting in a therapeutic effect in a mouse model of mammary cancer.
      It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a
      tripartite vaccine can significantly impact the quality of immune responses
      elicited against a tumor-associated glycopeptide. The unique adjuvant properties
      of Pam3 CysSK4 , which can reduce the suppressive function of regulatory T cells
      and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for
      the superior properties of the vaccine candidate 1. 

PMID- 24890743
TI  - Route of delivery following successful external cephalic version.
AB  - OBJECTIVE: To evaluate the delivery route and the indications for cesarean
      delivery after successful external cephalic version (ECV). METHODS: A
      retrospective matched case-control study was conducted at a hospital in Lisbon,
      Portugal, between 2002 and 2012. Each woman who underwent successful ECV (n = 44)
      was compared with the previous and next women who presented for labor management
      and who had the same parity and a singleton vertex pregnancy at term (n = 88).
      The outcome measures were route of delivery, indications for cesarean delivery,
      and incidence of nonreassuring fetal status. RESULTS: Attempts at ECV were
      successful in 62 (46%) of 134 women, and 44 women whose fetuses remained in a
      cephalic presentation until delivery were included in the study. The rates of
      intrapartum cesarean delivery and operative vaginal delivery did not differ
      significantly between cases and controls (intrapartum cesarean delivery, 9 [20%]
      vs 16 [18%], P = 0.75; operative vaginal delivery, 14 [32%] vs 19 [22%], P =
      0.20). The indications for cesarean delivery after successful ECV did not differ;
      in both groups, cesarean delivery was mainly performed for labor arrest disorders
      (cases, 6 [67%] vs controls, 13 [81%]; P = 0.63). CONCLUSION: Successful ECV was
      not associated with increased rates of intrapartum cesarean delivery or operative
      vaginal delivery.

PMID- 24890744
TI  - Healthcare-associated infections in gynecology and obstetrics at a university
      hospital in the Czech Republic.
AB  - OBJECTIVE: To determine the spectrum of etiology and the incidence of healthcare
      associated infections (HAIs) among gynecologic and obstetric patients. METHODS:
      In a descriptive survey, data were analyzed from in-patients at the Department of
      Gynecology and Obstetrics, University Hospital and Faculty of Medicine in Hradec
      Kralove, Czech Republic, between January 2007 and December 2011. RESULTS: Among
      21 937 patients treated during the study period, there were 189 (0.86%) cases of
      HAI. Gynecologic patients had a higher incidence of HAIs (1.31%) compared with
      pregnant women (0.60%). The incidence of HAI was 0.13% after laparoscopic
      surgery, 0.63% after a minor gynecologic intervention, and 3.73% after major
      surgery. Vaginal delivery (0.36%) represented a low risk of HAI. Compared with
      vaginal delivery, the incidence of HAI increased twofold for planned cesarean
      delivery (0.64%), and tenfold for emergency cesarean delivery (3.63%). The
      majority of causative microorganisms (72.7%) were susceptible to penicillin
      antibiotics. None of the patients died as a result of HAI. CONCLUSION: The
      incidence of HAIs at a university hospital in the Czech Republic was very low.
      Antibiotic resistance was only a minor problem, and the incidence of
      multiresistant strains was rare.

PMID- 24890745
TI  - Hysteroscopic findings of starry sky appearance and impregnated cobwebs in
      endometrial tuberculosis.

PMID- 24890747
TI  - Abbreviated (12-hour) versus traditional (24-hour) postpartum magnesium sulfate
      therapy in severe pre-eclampsia.
AB  - OBJECTIVE: To compare the use of magnesium sulfate for 12 hours versus 24 hours
      in postpartum women with stable severe pre-eclampsia. METHODS: In 2011, an open
      randomized clinical trial was conducted with 120 postpartum women with severe pre
      eclampsia who gave birth at a tertiary hospital in Brazil; 60 women received
      magnesium sulfate for 24 hours and 60 for 12 hours. The analysis was by intention
      to-treat and the intervention was not masked. RESULTS: Abbreviated (12-hour)
      magnesium sulfate therapy was associated with less exposure to the drug, and
      clinical outcomes were similar in both groups. No woman developed eclampsia and
      there was no need to re-initiate treatment after completing the scheduled
      magnesium sulfate therapy in either group. Magnesium sulfate therapy was extended
      in only three women in the 12-hour group. In addition, in this group, significant
      reductions were found in the duration of postpartum use of an indwelling bladder
      catheter, the time to ambulation, and the time to maternal contact with the
      newborn. CONCLUSION: Abbreviated postpartum magnesium sulfate therapy in patients
      with stable severe pre-eclampsia was associated with less drug exposure, similar
      outcomes, and benefits such as a reduction in the time to contact with the
      newborn. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT1408979.

PMID- 24890746
TI  - Medical eligibility, contraceptive choice, and intrauterine device acceptance
      among HIV-infected women receiving antiretroviral therapy in Lilongwe, Malawi.
AB  - OBJECTIVE: To determine medical eligibility for contraceptive use, contraceptive
      preference, and acceptance of a copper intrauterine device (IUD) among a cohort
      of HIV-infected women receiving antiretroviral therapy (ART). METHODS: All HIV
      infected women who received ART and sought contraceptive services at the
      Lighthouse clinic, an integrated HIV/ART clinic in Lilongwe, Malawi, between
      August and December 2010 were invited to participate in a structured interview.
      Eligibility and preference for the following contraceptive methods were assessed:
      combined hormonal contraceptives, progestogen-only pills, copper IUD, injectable
      depot medroxyprogesterone acetate (DMPA), and contraceptive implants. RESULTS:
      The final sample included 281 women; five were pregnant. The remaining 276 women
      were eligible for at least three contraceptive methods, with 242 (87.7%) eligible
      for all five methods evaluated. After counseling, 163 (58.0%) selected DMPA and
      98 (34.9%) selected an IUD as their preferred contraceptive method. Regardless of
      their method of choice, 222 (79.0%) women agreed to have an IUD placed on the
      same day. CONCLUSION: Most methods of contraception are safe for use by HIV
      infected women. Approximately 80% of the women were willing to receive an IUD.
      Efforts must be made to increase education about, and access to, long-acting
      reversible methods that may be acceptable and appropriate contraceptive options
      for HIV-infected women.

PMID- 24890748
TI  - Imatinib-associated matrix metalloproteinase suppression in p16-positive squamous
      cell carcinoma compared to HPV-negative HNSCC cells in vitro.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of
      cancer worldwide. The growth and invasion of HNSCC are strongly influenced by the
      extracellular matrix (ECM), which is modified by matrix metalloproteinases
      (MMPs). The MMP family is still relevant to cancer research, as it promotes
      malignant transformation, cell proliferation and modulation of angiogenesis even
      in the early stages of cancer. The proteolytic processing of bioactive molecules
      by MMP-14 (MT1-MMP) causes severe abnormalities in connective tissue, defective
      angiogenesis and premature death. MMP-2 (gelatinase A) and MMP-14 also play a
      role in degradation of basement membrane and cell carcinoma invasion. Imatinib
      blocks the PTK receptor c-kit and forestalls its PTK activity. The aim of the
      present study was to investigate the expression pattern of MMP-14 and MMP-2 in
      human papilloma virus (HPV)-negative and p16-positive SCC and to evaluate the
      chemosensitivity of the tumour cells to the chemotherapeutic agents, imatinib and
      5-fluorouracil (5-FU). We incubated the SCC cell lines with imatinib (18 and 30
      umol/ml) and 5-FU (1 and 5 umol/ml) and detected MMP-14 and MMP-2 by
      immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) after 48, 72,
      120, 192 and 240 h. We detected expression of MMP-2 and MMP-14 in all incubated
      tumour cell lines. With imatinib in particular, we found a reliable trend towards
      decreased MMP-2 and MMP-14 expression levels in p16-positive and p16-negative SCC
      tumour cell lines in addition to an induced apoptotic effect. We found
      statistically significant imatinib-induced suppression of MMP-2- and MMP-14,
      dependent on the incubation time and the cell line. We detected a significant
      suppression of MMP-2 and MMP-14 especially in p16-negative HNSCC14C cells after
      prolonged treatment time with imatinib. Dose escalation of imatinib and 5-FU had
      no statistically significant effect on the expression of MMP-2 or MMP-14. The p16
      positive SCC cells exhibited higher expression of total protein. We detected a
      significant suppression of MMP-2 and MMP-14 in all the incubated SCC cell lines,
      partially after treatment with imatinib. We found higher suppression of MMP-2 in
      the CERV196 cells after incubation with imatinib. We detected a reliable trend
      towards increased chemosensitivity of p16-positive tumour cells in vitro after
      treatment with imatinib. Extended studies and clinical trials are needed to
      further investigate these findings in HPV-associated HNSCC.

PMID- 24890749
TI  - Measuring fluxes of trace gases and energy between ecosystems and the atmosphere 
      the state and future of the eddy covariance method.
AB  - The application of the eddy covariance flux method to measure fluxes of trace gas
      and energy between ecosystems and the atmosphere has exploded over the past 25
      years. This opinion paper provides a perspective on the contributions and future
      opportunities of the eddy covariance method. First, the paper discusses the pros
      and cons of this method relative to other methods used to measure the exchange of
      trace gases between ecosystems and the atmosphere. Second, it discusses how the
      use of eddy covariance method has grown and evolved. Today, more than 400 flux
      measurement sites are operating world-wide and the duration of the time series
      exceed a decade at dozens of sites. Networks of tower sites now enable scientists
      to ask scientific questions related to climatic and ecological gradients,
      disturbance, changes in land use, and management. The paper ends with discussions
      on where the field of flux measurement is heading. Topics discussed include role
      of open access data sharing and data mining, in this new era of big data, and
      opportunities new sensors that measure a variety of trace gases, like volatile
      organic carbon compounds, methane and nitrous oxide, and aerosols, may yield. 

PMID- 24890751
TI  - Anti-inflammatory prostaglandins for the prevention of preterm labour.
AB  - Preterm birth occurs in 10-12% of pregnancies and is the primary cause of
      neonatal mortality and morbidity. Tocolytic therapies have long been the focus
      for the prevention of preterm labour, yet they do not significantly improve
      neonatal outcome. A direct causal link exists between infection-induced
      inflammation and preterm labour. As inflammation and infection are independent
      risk factors for poor neonatal outcome, recent research focus has been shifted
      towards exploring the potential for anti-inflammatory strategies. Nuclear factor
      kappa B (NFkappaB) is a transcription factor that controls the expression of many
      labour-associated genes including PTGS2 (COX2), prostaglandins (PGs) and the
      oxytocin receptor (OXTR) as well as key inflammatory genes. Targeting the
      inhibition of NFkappaB is therefore an attractive therapeutic approach for both
      the prevention of preterm labour and for reducing neonatal exposure to
      inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the
      cyclopentenone PG 15-deoxy-Delta(12,14)PGJ2 (15d-PGJ2) exhibits anti-inflammatory
      properties via the inhibition of NFkappaB in human amniocytes, myocytes and
      peripheral blood mononuclear cells in vitro. 15d-PGJ2 also delays inflammation
      induced preterm labour in the mouse and significantly increases pup survival.
      This review examines the current understanding of inflammation in the context of
      labour and discusses how anti-inflammatory PGs may hold promise for the
      prevention of preterm labour and improved neonatal outcome. 

PMID- 24890750
TI  - Self-reported pain severity is associated with a history of coronary heart
      disease.
AB  - BACKGROUND: Previous studies have found an association between chronic pain and
      cardiovascular (CV) mortality. OBJECTIVE: To explore the relationship between the
      severity of pain and non-fatal CV disease. METHODS: A total of 45,994 adults
      randomly selected from general practice registers in Manchester and Aberdeen were
      posted a survey, which included a Chronic Pain Grade questionnaire, pain manikin
      and questions about lifestyle and medical history. A single component measuring
      pain severity was extracted using factor analysis. Logistic regression was used
      to test for an association between quintiles of pain severity and a history of CV
      disease, adjusting for confounders. RESULTS: Of the 15,288 responders, 61% (n =
      9357) reported pain for >= 1 day in the past month. Compared with the first
      (lowest) pain severity quintile, the fully adjusted odds ratio for heart attack
      in the second severity quintile was 1.25 (95% confidence interval 0.68, 2.30);
      third quintile: 1.65 (0.93, 2.94); fourth quintile: 1.76 (1.00, 3.11) and fifth
      (highest) quintile 2.47 (1.43, 4.28). Corresponding figures for angina (excluding
      heart attack) were: 1.79 (0.93, 3.45), 1.91 (1.00, 3.62), 1.03 (0.50, 2.11) and
      3.17 (1.71, 5.85). CONCLUSION: A history of CV disease is reported more often in
      those with severe pain than would be expected by chance, even when adjusting for
      shared risk factors.

PMID- 24890752
TI  - Innate immunity and inflammation of the bovine female reproductive tract in
      health and disease.
AB  - Mammalian reproductive physiology and the development of viviparity co-evolved
      with inflammation and immunity over millennia. Many inflammatory mediators
      contribute to paracrine and endocrine signalling, and the maintenance of tissue
      homeostasis in the female reproductive tract. However, inflammation is also a
      feature of microbial infections of the reproductive tract. Bacteria and viruses
      commonly cause endometritis, perturb ovarian follicle development and suppress
      the endocrine activity of the hypothalamus and pituitary in cattle. Innate
      immunity is an evolutionary ancient system that orchestrates host cell
      inflammatory responses aimed at eliminating pathogens and repairing damaged
      tissue. Pattern recognition receptors on host cells bind pathogen-associated
      molecular patterns and damage-associated molecular patterns, leading to the
      activation of intracellular MAPK and NFkappaB signalling pathways and the release
      of inflammatory mediators. Inflammatory mediators typically include the
      interleukin cytokines IL1beta and IL6, chemokines such as IL8, interferons and
      prostaglandins. This review outlines the mechanisms of inflammation and innate
      immunity in the bovine female reproductive tract during health and disease
      condition. 

PMID- 24890753
TI  - Implementing a major stream in mental health nursing: barriers to effectiveness.
AB  - Changes to the educational preparation of the nursing workforce in mental health
      continue to have profound effects on the availability of sufficient numbers of
      skilled graduates willing to work in this field. The longevity of the problem has
      focused attention on possible solutions. Introducing a major stream in mental
      health nursing in undergraduate Bachelor of Nursing programmes was proposed and
      supported as a potentially beneficial strategy, adopted by some Australian
      universities. Despite the promise invested in this strategy, systematic
      evaluations to determine the effectiveness or otherwise of this approach were not
      initiated. A qualitative exploratory study was undertaken with Australian
      universities, which had implemented the major stream, regarding their experiences
      and observed outcomes. In-depth interviews were conducted with a mental health
      nurse academic from each university. The barriers to the effectiveness of the
      major in mental health nursing are the specific focus of this paper. Thematic
      data analysis revealed three main barriers: clinical placements, lack of support
      from other academics, and integrated curricula. These barriers substantially
      limited the effectiveness of this strategy - in some instances, leading to the
      programme's termination - and must be assertively addressed to maximize the
      potential of the major in mental health nursing. 

PMID- 24890754
TI  - Differential responses of arbuscular mycorrhizal fungi to nitrogen addition in a
      near pristine Tibetan alpine meadow.
AB  - Elucidating the responses of soil microbial abundance and community composition
      to nitrogen (N) addition is important for predicting ecosystem function under
      increased atmospheric N deposition. We examined the arbuscular mycorrhizal (AM)
      fungal community under three N forms (NH4(+)-N, NO3(-)-N, and NH4NO3-N) and two N
      rates (1.5 and 7.5 g N m(-2) year(-1)) in an alpine meadow of the Qinghai-Tibetan
      Plateau. AM fungal extraradical hyphal density was significantly decreased by
      NH4(+)-N in May, but was not affected by N form nor N rate in August. N rate, but
      not N form, significantly affected AM fungal spore density; high N rate decreased
      spore density. No direct N addition effect was observed on AM fungal community;
      however, soil available phosphorus, pH, and NO3(-)-N were considered as important
      factors that influenced AM fungal community composition. Structural equation
      model results showed that N rate, not N form, strongly affected soil
      characteristics, which directly influenced community compositions of plants and
      AM fungi, as well as spore density. Therefore, AM fungal community was influenced
      by N addition, primarily because of altered soil characteristics, and partially
      by a modified plant community, but not or just slightly by direct N addition
      effects in this alpine meadow ecosystem.

PMID- 24890755
TI  - Clinical impact of Clostridium difficile colonization.
AB  - Clostridium difficile can cause antibiotic-associated diarrhea in hospitalized
      patients. Asymptomatic colonization by C. difficile is common during the neonatal
      period and early infancy, ranging from 21% to 48%, and in childhood. The
      colonization rate of C. difficile in adult hospitalized patients shows geographic
      variation, ranging from 4.4% to 23.2%. Asymptomatic carriage in neonates caused
      no further disease in many studies, whereas adult patients colonized with
      toxigenic C. difficile were prone to the subsequent development of C. difficile
      associated diarrhea (CDAD). However, the carriage of nontoxigenic C. difficile
      strains appears to prevent CDAD in hamsters and humans. Risk factors for C.
      difficile colonization include recent hospitalization, exposure to antimicrobial
      agents or gastric acid-suppressing drugs (such as proton-pump inhibitors and H2
      blockers), a history of CDAD or cytomegalovirus infection, the presence of an
      underlying illness, receipt of immunosuppressants, the presence of antibodies
      against toxin B, and Toll-like receptor 4 polymorphisms. Asymptomatic C.
      difficile carriers are associated with significant skin and environmental
      contamination, similar to those with CDAD, and contact isolation and hand-washing
      practices should therefore be employed as infection control policies for the
      prevention of C. difficile spread. Treating patients with asymptomatic C.
      difficile colonization with metronidazole or vancomycin is not suggested by the
      currently available evidence. In conclusion, asymptomatic C. difficile
      colonization may lead to skin and environmental contamination by C. difficile,
      but more attention should be paid to the clinical impact of those with C.
      difficile colonization. 

PMID- 24890756
TI  - Strongyloides stercoralis disseminated infection in a patient misdiagnosed with
      chronic asthmatic bronchitis.

PMID- 24890757
TI  - Understanding sickness presenteeism through the experience of immigrant workers
      in a context of economic crisis.
AB  - BACKGROUND: Previous economic recessions show that immigrant workers may
      experience longer periods of unemployment, a situation that may lead employees to
      presenteeism, the act of working in spite of a health problem. This study
      explored perceptions about the factors that lead to presenteeism in immigrant
      workers considering the context of economic crisis. METHODS: Six focus group
      discussions were held (February 2012), with men and women from Colombia, Ecuador,
      and Morocco (n=44) living in Spain and selected by theoretical sample. A
      qualitative content analysis was performed. RESULTS: Four categories were
      identified as factors that influence the occurrence of presenteeism in a context
      of economic crisis: poor employment conditions, fear of unemployment,
      employer/employee relationship, and difficulties in finding temporary replacement
      workers. Furthermore, musculoskeletal, respiratory, and mental problems were
      related to presenteeism. CONCLUSIONS: It is important to develop strategies to
      protect workers from negative working conditions that are associated with
      deterioration of health.

PMID- 24890758
TI  - Ferredoxin:thioredoxin reductase is required for proper chloroplast development
      and is involved in the regulation of plastid gene expression in Arabidopsis
      thaliana.

PMID- 24890759
TI  - Temporal trends in head and neck cancer surgery reconstruction.
AB  - BACKGROUND: The purpose of this study was to analyze changing trends in head and
      neck cancer reconstructive surgery and analyze the effect of surgeon and hospital
      volume. METHODS: Data from the Nationwide Inpatient Sample (NIS) for 133,850
      patients who underwent a major ablative procedure for a malignant oral cavity,
      laryngeal, hypopharyngeal, or oropharyngeal neoplasm in 1993 to 2010 were
      analyzed using cross-tabulations and multivariate regression. RESULTS:
      Reconstructive surgery in 2001 to 2010 was significantly associated with prior
      radiation (odds ratio [OR] = 2.6; 95% confidence interval [95% CI] = 1.4-4.9),
      comorbidity (OR = 1.6; 95% CI = 1.1-2.2), laryngeal cancer (OR = 0.7; 95% CI =
      0.6-0.9), oropharyngeal cancer (OR = 0.5; 95% CI = 0.4-0.7), high-volume
      hospitals (OR = 3.9; 95% CI = 1.5-10.2), and high-volume surgeons (OR = 2.0; 95%
      CI = 1.1-3.9), compared to 1993-2000. Reconstruction by high-volume surgeons was
      significantly associated with prior radiation (OR = 1.8; 95% CI = 1.1-3.1) and
      lower in-hospital mortality (OR = 0.3; 95% CI = 0.1-1.0). A statistically
      significant negative correlation was observed between high-volume surgeons and
      length of hospitalization and hospital-related costs. CONCLUSION: These data
      reflect changing trends in head and neck cancer reconstructive surgery, with
      meaningful differences in the type of surgical care provided by high-volume
      surgeons.

PMID- 24890760
TI  - Core competency model for the family planning public health nurse.
AB  - OBJECTIVES: A core competency model for family planning public health nurses has
      been developed, using a three stage Delphi Method with an expert panel of 40
      family planning senior administrators, community/public health nursing faculty
      and seasoned family planning public health nurses. DESIGN AND SAMPLE: The initial
      survey was developed from the 2011 Title X Family Planning program priorities.
      The 32-item survey was distributed electronically via SurveyMonkey((r)). RESULTS:
      Panelist attrition was low, and participation robust resulting in the final 28
      item model, suggesting that the Delphi Method was a successful technique through
      which to achieve consensus. CONCLUSIONS: Competencies with at least 75% consensus
      were included in the model and those competencies were primarily related to
      education/counseling and administration of medications and contraceptives. The
      competencies identified have implications for education/training, certification
      and workplace performance.

PMID- 24890761
TI  - In vitro-in vivo correlation strategy applied to an immediate-release solid oral
      dosage form with a biopharmaceutical classification system IV compound case
      study.
AB  - The ability to predict in vivo response of an oral dosage form based on an in
      vitro technique has been a sought after goal of the pharmaceutical scientist.
      Dissolution testing that demonstrates discrimination to various critical
      formulations or process attributes provides a sensitive quality check that may be
      representative or may be overpredictive of potential in vivo changes. Dissolution
      methodology with an established in vitro-in vivo relationship or correlation may
      provide the desired in vivo predictability. To establish this in vitro-in vivo
      link, a clinical study must be performed. In this article, recommendations are
      given in the selection of batches for the clinical study followed by potential
      outcome scenarios. The investigation of a Level C in vitro-in vivo correlation
      (IVIVC), which is the most common correlation for immediate-release oral dosage
      forms, is presented. Lastly, an IVIVC case study involving a biopharmaceutical
      classification system class IV compound is presented encompassing this strategy
      and techniques.

PMID- 24890762
TI  - A case of tumour necrosis factor-alpha inhibitor- and rituximab-induced plantar
      pustular psoriasis that completely resolved with tocilizumab.
AB  - Rituximab, a chimeric B-cell-depleting monoclonal antibody, is a well-established
      therapy for rheumatoid arthritis. It is emerging that classical psoriatic lesions
      and plantar pustular psoriasis (PPP) are cutaneous side-effects of this drug.
      Antitumour necrosis factor (anti-TNF) therapies have multiple documented side
      effects including PPP and psoriasis. We report a patient who has rheumatoid
      arthritis, who failed on anti-TNF therapies and then was commenced on rituximab.
      Subsequently she developed localized PPP. Due to deterioration of her joint
      disease she was switched to the interleukin-6 blocker tocilizumab, and the PPP
      resolved. 

PMID- 24890763
TI  - Protein secondary structure prediction from circular dichroism spectra using a
      self-organizing map with concentration correction.
AB  - Collecting circular dichroism (CD) spectra for protein solutions is a simple
      experiment, yet reliable extraction of secondary structure content is dependent
      on knowledge of the concentration of the protein--which is not always available
      with accuracy. We previously developed a self-organizing map (SOM), called
      Secondary Structure Neural Network (SSNN), to cluster a database of CD spectra
      and use that map to assign the secondary structure content of new proteins from
      CD spectra. The performance of SSNN is at least as good as other available
      protein CD structure-fitting algorithms. In this work we apply SSNN to a
      collection of spectra of experimental samples where there was suspicion that the
      nominal protein concentration was incorrect. We show that by plotting the
      normalized root mean square deviation of the SSNN predicted spectrum from the
      experimental one versus a concentration scaling-factor it is possible to improve
      the estimate of the protein concentration while providing an estimate of the
      secondary structure. For our implementation (51 data points 240-190 nm in nm
      increments) good fits and structure estimates were obtained if the NRMSD
      (normalized root mean square displacement, RMSE/data range) is <0.03; reasonable
      for NRMSD <0.05; and variable above this. We also augmented the reference
      database with 100% helical spectra and truly random coil spectra.

PMID- 24890764
TI  - Medical and interventional options to treat pulmonary embolism.
AB  - Venous thromboembolism remains one of the most common conditions. Pulmonary
      embolism carries a mortality rate of over 15 % in the first 3 months after
      diagnosis. Venous thromboembolism is the fourth leading cause of death in the
      Western world, and the third leading cause of cardiovascular death trailing
      myocardial infarction and stroke. This section highlights the medical and
      interventional options presently available to treat this potentially lethal
      disease.

PMID- 24890765
TI  - Strategies to prevent radial artery occlusion after transradial PCI.
AB  - Radial artery occlusion (RAO) is the most common structural consequence of
      transradial access (TRA) with an estimated incidence ranging from 2-10 %. Its
      occurrence is free of any major clinical consequences, especially at rest, with
      most if not all cases of digital ischemia occurring as a result of embolization,
      rather than RAO. The incidence of RAO is unacceptably high if "best practices"
      are not followed. Strategies to prevent RAO need to be implemented to preserve
      radial artery patency in order to exploit other benefits of TRA.

PMID- 24890766
TI  - Emerging therapeutic approaches to treat dyslipidemia.
AB  - Statins are safe, efficacious and the cornerstone of cardiovascular disease
      prevention strategies. A number of add-on therapies with complementary actions on
      the plasma lipid profile have been tested in large scale trials to see if they
      give incremental benefit. In particular, the 'HDL hypothesis' - that raising this
      lipoprotein will promote reverse cholesterol transport and reduce cardiovascular
      risk - has been examined using drugs such as dalcetrapib and niacin. So far,
      results have been negative, and this has raised questions over the nature of the
      association of HDL with atherosclerosis, and whether statins reduce
      cardiovascular risk through multiple mechanisms. There is still an unmet clinical
      need especially in those patients who cannot tolerate statins and those with
      severe hyperlipidemia, and so new therapeutic approaches have been developed.
      These show significant promise in terms of LDL-cholesterol lowering but
      significant challenges include cost, route of administration (subcutaneous
      injection) and side effects. Testing in major outcome trials will be required to
      demonstrate their clinical utility. 

PMID- 24890768
TI  - Localized epicarditis mimicking right atrial mass.

PMID- 24890769
TI  - Mediastinal hydatid cyst compressing the pulmonary artery and atrial septal
      defect: a rare association.

PMID- 24890770
TI  - The use of absorbable interceed((r)) pouch with double-layer skin closure for
      partial defect of breast.
AB  - Generally, a partial breast defect can be covered with surrounding breast tissue.
      However, when the tumor is located in the upper central and inner quadrant,
      simple closure with breast tissue is insufficient because rotation of breast
      tissue is difficult in this location. We introduce a surgical technique using an
      absorbable Interceed((r)) pouch with double-layer skin closure for a remnant
      defect. A total of 43 patients with breast cancer underwent conventional breast
      conserving surgery, following which an Interceed((r)) pouch with double-layer
      skin closure was applied for a remnant defect of the breast. Patients assessed
      their own cosmetic outcomes based on a four-point scoring system. The mean age of
      the patients and their mean body mass index were 51.2 years and 23.1 kg/m(2) ,
      respectively. Cosmetic outcomes were self-reported to be excellent in 13 cases
      (30.2%), good in 26 cases (60.5%), fair in three cases (7.0%), and poor in one
      case (2.3%). Postoperative complications occurred in two cases (4.6%). In
      conclusion, a use of an absorbable Interceed((r)) pouch with double-layer skin
      closure is a simple, feasible, ancillary surgical technique to correct an upper
      central and inner quadrant breast defect without significant complications.

PMID- 24890767
TI  - The urinary proteome and peptidome of renal cell carcinoma patients: a comparison
      of different techniques.
AB  - Renal cell carcinomas, originating from the renal cortex, account for about 80%
      of kidney primary malignancies. Small localized tumors rarely produce symptoms
      and diagnosis is often delayed until the disease is advanced. In contrast to
      other urological cancers, renal cell carcinomas are associated with a high degree
      of metastases and a low 5-year survival rate. The identification of diagnostic
      and prognostic markers, especially in the urine, remains an area of intense
      investigation. Different proteomic strategies have been applied so far to
      biomarker discovery in urine at the proteome or the peptidome level. Gel-based
      and gel-free strategies combined with mass spectrometry are the most-used
      strategies, have different success rates, and will be depicted here. We also
      prefigure a scenario in which the limitations of a single approach are overcome
      by applying new and complementary research strategies, relying on the excellent
      availability coupled to the intrinsic richness typical of urine samples. 

PMID- 24890771
TI  - Life history parameters of the cattle long-nosed sucking louse, Linognathus
      vituli.
AB  - Cattle sucking lice, Linognathus vituli (L.) (Phthiraptera: Linognathidae), were
      obtained from naturally infected cattle and maintained within 'arenas' affixed to
      the backs of cattle confined in controlled environment chambers maintained at a
      constant temperature of 15  degrees C. Temperatures measured within the arenas at
      an ambient temperature of 15  degrees C were constant at about 34  degrees C and
      only slightly above the temperature on nearby skin. The effect of temperature on
      egg development was determined using a gradient of temperatures between 25 
      degrees C and 41  degrees C. Eggs did not develop at temperatures of < 26 
      degrees C or > 39  degrees C. Survival of eggs was highest at temperatures of 30 
      degrees C and 35  degrees C. The earliest hatch was observed at 5 days post
      oviposition (at 33-35  degrees C). Development was extended to as long as 13 days
      at the lower temperatures. Kaplan-Meier survival probabilities were compared for
      lice kept at two densities in the arenas and showed there to be no effect of
      density on louse survival. Similarly, the mean number of eggs/louse/day over an 8
      day period was not influenced by louse density.

PMID- 24890774
TI  - Imaging: diagnostic value of ultrasonography in Sjogren's syndrome.
AB  - Salivary gland ultrasonography is a promising tool for the evaluation of
      Sjogren's syndrome. Cumulative data suggest that ultrasonography is comparable
      with older imaging modalities such as sialography and scintigraphy. However,
      certain issues remain to be addressed before it can be integrated into current or
      future classification systems.

PMID- 24890775
TI  - Osteoarthritis: Epigenetic clues into the molecular basis of OA.

PMID- 24890772
TI  - Heterogeneity of stromal cells in the human splenic white pulp. Fibroblastic
      reticulum cells, follicular dendritic cells and a third superficial stromal cell
      type.
AB  - At least three phenotypically and morphologically distinguishable types of
      branched stromal cells are revealed in the human splenic white pulp by
      subtractive immunohistological double-staining. CD271 is expressed in
      fibroblastic reticulum cells of T-cell zones and in follicular dendritic cells of
      follicles. In addition, there is a third CD2711- and CD271+/) stromal cell
      population surrounding T-cell zones and follicles. At the surface of follicles
      the third population consists of individually variable partially overlapping
      shells of stromal cells exhibiting CD90 (Thy-1), MAdCAM-1, CD105 (endoglin),
      CD141 (thrombomodulin) and smooth muscle alpha-actin (SMA) with expression of
      CD90 characterizing the broadest shell and SMA the smallest. In addition, CXCL12,
      CXCL13 and CCL21 are also present in third-population stromal cells and/or along
      fibres. Not only CD27+ and switched B lymphocytes, but also scattered IgD++ B
      lymphocytes and variable numbers of CD4+ T lymphocytes often occur close to the
      third stromal cell population or one of its subpopulations at the surface of the
      follicles. In contrast to human lymph nodes, neither podoplanin nor RANKL (CD254)
      were detected in adult human splenic white pulp stromal cells. The superficial
      stromal cells of the human splenic white pulp belong to a widespread cell type,
      which is also found at the surface of red pulp arterioles surrounded by a mixed T
      cell/B-cell population. Superficial white pulp stromal cells differ from
      fibroblastic reticulum cells and follicular dendritic cells not only in humans,
      but apparently also in mice and perhaps in rats. However, the phenotype of white
      pulp stromal cells is species-specific and more heterogeneous than described so
      far.

PMID- 24890777
TI  - Bone: Fighting osteoporosis black and blue.

PMID- 24890776
TI  - Current and emerging techniques for ANCA detection in vasculitis.
AB  - Detection of antineutrophil cytoplasmic antibodies (ANCAs) is a well-established
      diagnostic test used to evaluate suspected necrotizing vasculitis of small blood
      vessels. Conditions associated with these antibodies, collectively referred to as
      ANCA-associated vasculitides, include granulomatosis with polyangiitis (formerly
      known as Wegener granulomatosis), microscopic polyangiitis, and eosinophilic
      granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome). The
      diagnostic utility of ANCA testing depends on the type of assay performed and on
      the clinical setting. Most laboratories worldwide use standard indirect
      immunofluorescence tests (IFT) to screen for ANCA and then confirm positive IFT
      results with antigen-specific tests for proteinase 3 (PR3) and myeloperoxidase
      (MPO). Developments such as automated image analysis of immunofluorescence
      patterns, so-called third-generation PR3-ANCA and MPO-ANCA ELISA, and multiplex
      technology have improved the detection of ANCAs. However, challenges in routine
      clinical practice remain, including methodological aspects of IFT performance,
      the diverse antigen-specific assays available, the diagnostic value of testing in
      clinical settings and the prognostic value of serial ANCA monitoring in the
      prediction of disease relapse. This Review summarizes the available data on ANCA
      testing, discusses the usefulness of the various ANCA assays and advises on the
      clinical indications for the use of ANCA testing. 

PMID- 24890779
TI  - Fingerprint analysis and multi-ingredient quantitative analysis for quality
      evaluation of Xiaoyanlidan tablets by ultra high performance liquid
      chromatography with diode array detection.
AB  - A rapid and sensitive ultra high performance liquid chromatography method with
      diode array detection was developed for the fingerprint analysis and simultaneous
      determination of seven active compounds in Xiaoyanlidan (XYLD) tablets. The
      chromatographic separations were obtained on an Agilent Eclipse plus C18 column
      (50 * 2.1 mm id, 1.8 MUm) using gradient elution with water/formic acid (1%) and
      acetonitrile at a flow rate of 0.4 mL/min. Within 63 min, 36 peaks could be
      selected as the common peaks for fingerprint analysis to evaluate the
      similarities among several samples of XYLD tablets collected from different
      manufacturers. In quantitative analysis, seven compounds showed good regression
      (R > 0.9990) within test ranges and the recovery of the method was within the
      range of 95.9-104.3%. The method was successfully applied to the simultaneous
      determination of seven compounds in six batches of XYLD tablets. These results
      demonstrate that the combination of chromatographic fingerprint analysis and
      simultaneous multi-ingredient quantification using the ultra high performance
      liquid chromatography method with diode array detection offers a rapid,
      efficient, and reliable approach for quality evaluation of XYLD tablets. 

PMID- 24890778
TI  - Conformation-dependent backbone geometry restraints set a new standard for
      protein crystallographic refinement.
AB  - Ideal values of bond angles and lengths used as external restraints are crucial
      for the successful refinement of protein crystal structures at all but the
      highest of resolutions. The restraints in common use today have been designed on
      the assumption that each type of bond or angle has a single ideal value that is
      independent of context. However, recent work has shown that the ideal values are,
      in fact, sensitive to local conformation, and, as a first step towards using such
      information to build more accurate models, ultra-high-resolution protein crystal
      structures have been used to derive a conformation-dependent library (CDL) of
      restraints for the protein backbone [Berkholz et al. (2009) Structure 17, 1316
      1325]. Here, we report the introduction of this CDL into the phenix package and
      the results of test refinements of thousands of structures across a wide range of
      resolutions. These tests show that use of the CDL yields models that have
      substantially better agreement with ideal main-chain bond angles and lengths and,
      on average, a slightly enhanced fit to the X-ray data. No disadvantages of using
      the backbone CDL are apparent. In phenix, use of the CDL can be selected by
      simply specifying the cdl = True option. This successful implementation paves the
      way for further aspects of the context dependence of ideal geometry to be
      characterized and applied to improve experimental and predictive modeling
      accuracy. 

PMID- 24890780
TI  - Surgical Trends in the Treatment of Superior Labrum Anterior and Posterior
      Lesions of the Shoulder: Analysis of Data From the American Board of Orthopaedic
      Surgery Certification Examination Database.
AB  - BACKGROUND: After failure of nonoperative treatment, repair has long been the
      primary treatment option for symptomatic superior labrum anterior and posterior
      (SLAP) lesions of the shoulder. There is growing evidence to support both biceps
      tenotomy and tenodesis as effective alternative treatments for SLAP lesions.
      HYPOTHESES: For patients with isolated SLAP lesions, the frequency of SLAP repair
      has decreased, while treatment with biceps tenodesis and tenotomy has increased.
      Similar trends are expected in patients with SLAP lesions undergoing concomitant
      rotator cuff repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A
      query of the American Board of Orthopaedic Surgery part II database was performed
      from 2002 to 2011. The database was searched for patients with isolated SLAP
      lesions undergoing SLAP repair, open biceps tenodesis, arthroscopic biceps
      tenodesis, or biceps tenotomy. The database was then queried a second time for
      patients undergoing arthroscopic rotator cuff repair with concomitant SLAP
      repair, biceps tenodesis, or biceps tenotomy. RESULTS: From 2002 to 2011, there
      were 8963 cases reported for the treatment of an isolated SLAP lesion and 1540
      cases reported for the treatment of SLAP lesions with concomitant rotator cuff
      repair. For patients with isolated SLAP lesions, the proportion of SLAP repairs
      decreased from 69.3% to 44.8% (P < .0001), while biceps tenodesis increased from
      1.9% to 18.8% (P < .0001), and biceps tenotomy increased from 0.4% to 1.7% (P =
      .018). For patients undergoing concomitant rotator cuff repair, SLAP repair
      decreased from 60.2% to 15.3% (P < .0001), while biceps tenodesis or tenotomy
      increased from 6.0% to 28.0% (P < .0001). There was a significant difference in
      the mean age of patients undergoing SLAP repair (37.1 years) versus biceps
      tenodesis (47.2 years) versus biceps tenotomy (55.7 years) (P < .0001).
      CONCLUSION: Practice trends for orthopaedic board candidates indicate that the
      proportion of SLAP repairs has decreased over time, with an increase in biceps
      tenodesis and tenotomy. Increased patient age correlates with the likelihood of
      treatment with biceps tenodesis or tenotomy versus SLAP repair.

PMID- 24890781
TI  - Effect of Notchplasty in Anatomic Double-Bundle Anterior Cruciate Ligament
      Reconstruction.
AB  - BACKGROUND: The effects of notchplasty on the clinical outcome after anatomic
      double-bundle anterior cruciate ligament (ACL) reconstruction remain unclear.
      HYPOTHESIS: Anatomic ACL reconstruction with notchplasty would result in less
      risk of loss of extension and would provide adequate space for better graft
      healing, leading to better knee stability compared with anatomic ACL
      reconstruction without notchplasty. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: A total of 137 patients who underwent anatomic double
      bundle ACL reconstruction were included. Seventy-three patients without
      notchplasty were classified as the control group, and 64 patients with 2-mm
      notchplasty were classified as the notchplasty group. The following evaluation
      methods were used: loss of extension, patient's subjective feeling of limited
      extension and pain at passive full extension, muscle strength, manual laxity
      tests, KT-1000 arthrometer measurement, patellofemoral joint findings, Tegner
      score, Lysholm score, subjective scores, and time to return to sports. Tearing of
      the reconstructed ACL and additional synovectomy were recorded. Both tibial and
      femoral tunnel positions were measured using 2-view radiographs: a Rosenberg and
      a lateral view. RESULTS: Loss of extension was larger in the notchplasty group
      compared with controls (at 6 months: 0.8 degrees  vs 1.4 degrees , P = .012; at 2
      years: 0.4 degrees  vs 0.9 degrees , P = .0053). The number of patients with a
      feeling of limited extension was also larger in the notchplasty group (at 6
      months: 13 patients graded 1+ [somewhat limited] and 2 patients graded 2+ [very
      limited] vs 18 graded 1+ and 6 graded 2+, P = .015; at 2 years: 2 graded 1+ and 0
      graded 2+ vs 4 graded 1+ and 5 graded 2+, P = .011). Six patients in the
      notchplasty group required additional synovectomy because of the prolonged loss
      of extension, whereas no patient in the control group required additional
      synovectomy. There were no differences between groups regarding muscle strength,
      patellofemoral findings, Lysholm score, Tegner score, subjective scores, or time
      to return to sports. The KT-1000 arthrometer measurement was better in the
      notchplasty group (1.2 vs 0.4 mm, P = .0017). However, 6 patients in the
      notchplasty group showed an overconstrained knee (KT-1000 measurement <=-2 mm),
      compared with only 1 patient in the control group. There were no differences
      between groups in the other manual laxity tests or the tunnel positions.
      CONCLUSION: In anatomic double-bundle ACL reconstruction, anterior stability was
      improved and there were no harmful effects on patellofemoral joint findings by 2
      mm notchplasty; however, notchplasty likely caused overconstrained knee, leading
      to a need for additional synovectomy in some patients. In contrast, anatomic
      double-bundle ACL reconstruction without notchplasty did not increase the
      incidence of loss of extension or of graft failure.

PMID- 24890782
TI  - Correlation Between Clinical and Radiological Outcomes After Matrix-Induced
      Autologous Chondrocyte Implantation in the Femoral Condyles.
AB  - BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) is an
      established technique for the repair of knee chondral defects, although the
      correlation between clinical and radiological outcomes after surgery is poorly
      understood. PURPOSE: To determine the correlation between clinical and
      radiological outcomes throughout the postoperative timeline to 5 years after
      MACI. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: This
      retrospective study was undertaken in 83 patients (53 male, 30 female) with
      complete clinical and radiological follow-up at 1, 2, and 5 years after MACI. The
      mean age of patients was 38.9 years (range, 13-62 years), with a mean body mass
      index (BMI) of 26.6 kg/m(2) (range, 16.8-34.8 kg/m(2)), mean defect size of 3.3
      cm(2) (range, 1-9 cm(2)), and mean preoperative duration of symptoms of 9.2 years
      (range, 1-46 years). Patients indicated for MACI in this follow-up were 13 to 65
      years of age, although they were excluded if they had a BMI >35 kg/m(2), had
      undergone prior extensive meniscectomy, or had ongoing progressive inflammatory
      arthritis. Patients were assessed clinically using the Knee Injury and
      Osteoarthritis Outcome Score (KOOS). Magnetic resonance imaging (MRI) was used to
      evaluate the graft using a 1.5-T or 3-T clinical scanner; the MRI assessment
      included 8 parameters of graft repair (infill, signal intensity, border
      integration, surface contour, structure, subchondral lamina, subchondral bone,
      and effusion) based on the magnetic resonance observation of cartilage repair
      tissue (MOCART) score as well as an MRI composite score. The degree of an
      association between the MRI parameters and the KOOS subscales at each
      postoperative time point was assessed with the Spearman correlation coefficient
      (SCC), and significance was determined at P < .05. Ethics approval was obtained
      from the appropriate hospital and university Human Research Ethics Committees,
      and informed consent was gathered from all patients. RESULTS: The only MRI
      parameter displaying consistent evidence of an association with the KOOS
      subscales was effusion, with a pattern of increasing strength of correlations
      over time and statistically significant associations at 5 years with KOOS-Pain
      (SCC, 0.25; P = .020), KOOS-Activities of Daily Living (SCC, 0.26; P = .018), and
      KOOS-Sport (SCC, 0.32; P = .003). Apart from a significant correlation between
      subchondral lamina and KOOS-Sport at 1 year (SCC, 0.27; P = .016), no further
      significant findings were observed. CONCLUSION: Apart from some consistent
      evidence of an association between the KOOS and effusion, this analysis
      demonstrated a limited correlative capacity between clinical and radiological
      outcomes up to 5 years after surgery.

PMID- 24890783
TI  - Child abuse, disruptive behavior disorders, depression, and salivary cortisol
      levels among institutionalized and community-residing boys in Mongolia.
AB  - INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis activity is related to
      childhood disruptive behavior disorders and to exposure to abuse and neglect.
      This study explores the relationship of diurnal salivary cortisol levels with
      oppositional defiant disorder (ODD) and caregiver attitudes toward physical
      punishment among boys in Mongolia. METHODS: Salivary cortisol was collected in
      the home or institution 4 times daily for 4 days from 46 boys, aged 4-10 years,
      in Ulaanbaatar, Mongolia. Caregivers rated child disruptive behavior symptoms,
      attitudes toward physical punishment, and community violence exposures. Mixed
      effects models were used to estimate the association of psychopathology and
      caregiver attitudes with salivary cortisol levels. RESULTS: Boys meeting criteria
      for ODD displayed consistently lower diurnal salivary cortisol levels compared to
      boys without ODD diagnoses. Controlling for ODD diagnosis, boys with depression
      showed higher cortisol levels throughout the day. No other diagnosis was
      associated with cortisol levels. Psychiatric diagnosis accounted for 17% of
      between individual variations in cortisol levels unexplained by the covariates.
      In a separate model, caregivers' beliefs regarding physical punishment accounted
      for 11% of between individual differences: boys with caregivers who stated
      physical punishment was necessary for discipline displayed hypocortisolism.
      Institutionalization did not associate with cortisol levels. DISCUSSION: Salivary
      cortisol data from a non-Western naturalistic setting support an association of
      reduced basal HPA activity with disruptive behavior disorders and caregiver
      attitudes toward discipline. These findings suggest HPA functioning may be a
      reflection of or mediate disruptive behavior disorders in children across ethnic
      and cultural settings.

PMID- 24890785
TI  - Linking the activity of bortezomib in multiple myeloma and autoimmune diseases.
AB  - Since their introduction to the clinic 10 years ago, proteasome inhibitors have
      become the cornerstone of anti-multiple myeloma therapy. Despite significant
      progress in understanding the consequences of proteasome inhibition, the unique
      activity of bortezomib is still unclear. Disappointing results from clinical
      trials with bortezomib in other malignancies raise the question of what makes
      multiple myeloma so sensitive to proteasome inhibition. Successful administration
      of bortezomib in various immunological disorders that exhibit high antibody
      production suggests that the balance between protein synthesis and degradation is
      a key determinant of sensitivity to proteasome inhibition because a high rate of
      protein production is a shared characteristic in plasma and myeloma cells.
      Initial or acquired resistance to bortezomib remains a major obstacle in the
      clinic as in vitro data from cell lines suggest a key role for the beta5 subunit
      mutation in resistance; however the mutation was not found in patient samples.
      Recent studies indicate the importance of selecting for a subpopulation of cells
      that produce lower amounts of paraprotein during bortezomib therapy. 

PMID- 24890786
TI  - Patient-centered research to inform patient-centered care for adolescents and
      young adults (AYAs) with cancer.

PMID- 24890784
TI  - Exon microarray analysis of human dorsolateral prefrontal cortex in alcoholism.
AB  - BACKGROUND: Alcohol abuse is associated with cellular and biochemical
      disturbances that impact upon protein and nucleic acid synthesis, brain
      development, function, and behavioral responses. To further characterize the
      genetic influences in alcoholism and the effects of alcohol consumption on gene
      expression, we used a highly sensitive exon microarray to examine mRNA expression
      in human frontal cortex of alcoholics and control males. METHODS: Messenger RNA
      was isolated from the dorsolateral prefrontal cortex (dlPFC; Brodmann area 9) of
      7 adult alcoholic (6 males, 1 female, mean age 49 years) and 7 matched controls.
      Affymetrix Human Exon 1.0 ST array was performed according to standard procedures
      and the results analyzed at the gene level. Microarray findings were validated
      using quantitative reverse transcription polymerase chain reaction, and the
      ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA).
      RESULTS: Decreased mRNA expression was observed for genes involved in cellular
      adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system
      development (e.g., LRP2, UGT8, GLDN), and signaling (e.g., RASGRP3, LGR5) with
      influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA
      identified disturbances in network functions associated with neurological disease
      and development including cellular assembly and organization impacting on
      psychological disorders. CONCLUSIONS: Our data in alcoholism support a reduction
      in expression of dlPFC mRNA for genes involved with neuronal growth,
      differentiation, and signaling that targets white matter of the brain.

PMID- 24890787
TI  - Safety and efficacy of cryoprecipitate-poor plasma as a replacement fluid for
      therapeutic plasma exchange in thrombotic thrombocytopenic purpura: a single
      center retrospective evaluation.
AB  - INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic
      microangiopathy caused by decreased activity of ADAMTS13, resulting in reduced
      clearance of ultralarge von Willebrand factor (VWF) multimers. Treatment of TTP
      is therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma
      (FFP). Cryoprecipitate-poor plasma (CPP) is a plasma product with lower
      concentrations of large VWF multimers, and similar amounts of ADAMTS13. CPP is
      regarded as at least as efficacious as FFP in TTP but evidence of additional
      benefits has not been demonstrated. Furthermore, there are limited data on the
      frequency of adverse events associated with CPP. MATERIAL AND METHODS: In our
      center, the choice between CPP and FFP is performed before the 1st TPE session at
      the physicians' discretion. Here, we retrospectively evaluated the efficacy and
      safety of CPP based on the number of sessions, volume of plasma exposure,
      frequency of exacerbations/relapses, and adverse events. RESULTS: Fourteen
      patients with newly diagnosed TTP were included in this analysis. The proportion
      of CPP:FFP use was 5:9. There were no significant differences in age, gender,
      initial hemoglobin, platelet count, LDH, or etiology of TTP between groups. We
      observed a trend toward a higher number of TPE sessions and higher plasma
      exposure in CPP, compared to FFP-treated patients. Acute exacerbations were more
      frequent among patients treated with CPP (OR 26.6; 95%CI 1.01-703.51; P = 0.03).
      Mild allergic reactions were the most common treatment-related adverse event in
      both groups. DISCUSSION: Our data suggest that CPP should not be used as 1st line
      treatment for newly diagnosed TTP patients.

PMID- 24890788
TI  - The plexin C1 receptor promotes acute inflammation.
AB  - Acute inflammation is the pathophysiological basis of important clinical
      conditions associated with organ failure. The initial inflammatory response is
      controlled by the chemokine system, yet recent data have indicated that the
      neuronal guidance cues are significantly involved in the orchestration of this
      process. Previous work has shown the proinflammatory capacity of the guidance cue
      semaphorin (Sema) 7a, but the role of one of its target receptors, the plexin C1
      (PLXNC1) receptor is to date unknown. We report here that PLXNC1 is expressed
      outside the nervous system and induced during acute inflammation. PLXNC1(-/-)
      mice with C57BL/6 background demonstrated decreased inflammatory responses during
      zymosan A (ZyA)-induced peritonitis. Subsequent in vivo studies revealed altered
      rolling, adhesion, and transmigration properties of PLXNC1(-/-) leukocytes.
      Blockade of PLXNC1 was associated with attenuated chemotactic transendothelial
      migration properties in vitro. Studies in chimeric mice revealed that
      hematopoietic PLXNC1(-/-) animals demonstrated an attenuated inflammatory
      response. To probe the therapeutic potential of PLXNC1 we treated C57BL/6 WT mice
      with an anti-PLXNC1 antibody and a PLXNC1 binding peptide. Both of these
      interventions significantly dampened ZyA-induced peritonitis. These results
      implicate an important role of PLXNC1 during an acute inflammatory response and
      indicate PLXNC1 as a potential target for the control of conditions associated
      with acute inflammation. 

PMID- 24890789
TI  - Tenofovir disoproxil fumarate rescue therapy for HBV recurrence in two liver
      transplant recipients with previous multiple nucleo(s/t)ide treatment failures.

PMID- 24890790
TI  - Methamphetamine self-administration results in persistent dopaminergic pathology:
      implications for Parkinson's disease risk and reward-seeking.
AB  - Methamphetamine (Meth) abuse may be a risk factor for Parkinson's disease (PD); a
      problematic event as approximately 33 million people abuse Meth worldwide. The
      current study determined if a mild form of PD-like nigrostriatal pathology
      occurred following forced abstinence in Meth self-administering rats. The average
      daily intake of self-administered Meth was 3.6 +/- 0.2 mg/kg/3 h over 14
      sessions. Subsequently, animals were killed and the brains harvested at 1, 7, 28
      or 56 days of abstinence. Post mortem, tyrosine hydroxylase (TH) immunostaining
      in the dorsal striatum progressively decreased throughout abstinence, reaching a
      50% loss at 56 days. In the substantia nigra, there was marked reduction of TH+
      cells, and Fluorogold (retrograde tracer) transport from the striatum to the
      nigra, at 28 and 56 days after Meth. Thus, Meth-induced progressive nigrostriatal
      damage occurred retrogradely, similar to PD pathology. The mesolimbic dopamine
      pathway [i.e. ventral tegmental area (VTA) and nucleus accumbens (NAc)], critical
      for Meth-induced reward, was also evaluated. TH immunostaining was decreased in
      the NAc-core at 28 and 56 days of forced abstinence, while staining in the
      dorsomedial NAc-shell was preserved. Accordingly, TH+ cell loss was evident in
      the lateral VTA, the origin of projections to the NAc-core, but not the medial
      VTA where NAc-shell projections originate. Thus, after Meth-taking ceased, a time
      dependent, progressive degeneration occurred within nigrostriatal projections
      that eventually engulfed lateral mesolimbic projections. This pathological
      pattern is consistent with a trajectory for developing PD; therefore, these
      findings provide preclinical support for Meth abuse to increase vulnerability to
      developing PD. 

PMID- 24890791
TI  - Cooperative complexation of amino acid derivatives to platinum acetylide-based
      bolaamphiphile.
AB  - A platinum(II) acetylide-based bolaamphiphile equipped with two peripheral B18C6
      moieties has been successfully prepared, which demonstrates cooperative
      recognition behavior toward l-alanine ester salt in chloroform. In a polar
      methanol/chloroform (3/1, v/v) medium, the amino acid additives influence the
      aggregation of the bolaamphiphile significantly, leading to the morphological
      transition from nanospherical to disordered structures. The adaptive properties
      of the current host-guest binary system will benefit the development of stimuli
      responsive supramolecular materials. 

PMID- 24890792
TI  - H2 and O2 activation--a remarkable insight into hydrogenase.
AB  - This article summarizes the development of a range of organometallic, biomimetic
      analogues of [NiFe]hydrogenases and their employment in a new generation of H2 
      O2 fuel cells. It begins with a summary of O2 -sensitive and O2 -tolerant enzyme
      chemistry before detailing the properties and functionality of our biomimetic
      complexes, including: the first ever fully functional model, selective H2 and O2
      activation, and the first catalyst using only common metals. These systems are
      centered on Ni-Fe, Ni-Ru, Ir-Ir, and Rh-Rh cores and use a range of ligands that
      all follow a set of design principles described herein. 

PMID- 24890793
TI  - Bafilomycin A1 inhibits autophagy and induces apoptosis in MG63 osteosarcoma
      cells.
AB  - The purpose of the present study was to investigate the effects of bafilomycin A1
      (BafA1) on proliferation, apoptosis and autophagy in MG63 osteosarcoma cells. The
      growth rate of MG63 cells was determined using a Cell Counting Kit-8 assay. The
      mitochondrial membrane potential (Deltapsi) was measured using a fluorescent
      probe, JC-1, and the inhibition of autophagy and apoptosis was monitored by
      transmission electron microscopy. In addition, the inhibition of autophagy was
      monitored by western blot analysis of microtubule-associated protein 1 light
      chain 3 (LC3), and the ratio of LC3-II/LC3-I protein levels was calculated as an
      indicator of the extent of autophagy. Furthermore, the expression levels of
      specific proteins associated with autophagy, including p53, Beclin1 and p62, were
      detected in cultured MG63 cells by western blotting. It was shown that the
      viability of MG63 cells was inhibited following the use of BafA1, and an
      induction in the expression levels of the apoptosis-related protein p53 and the
      autophagic protein Beclin1 was detected. Furthermore, a collapse in Deltapsi was
      observed, together with an induction of apoptotic cell death, following treatment
      with BafA1. Therefore, following BafA1-mediated inhibition of autophagy, the
      inhibition of MG63 cell proliferation and induction of apoptosis were observed. 

PMID- 24890794
TI  - Magnetostrictive particle based biosensors for in situ and real-time detection of
      pathogens in water.
AB  - Biosensors for in situ detection of pathogenic bacteria in liquid are developed
      using magnetostrictive particles (MSP) as the sensor platform. The sensing
      elements used are phage E2 against Salmonella typhimurium, monoclonal antibody
      against Listeria monocytogenes, polyclonal antibody against Escherichia coli, and
      polyclonal antibody against Staphylococcus aureus, respectively. These biosensors
      were characterized in cultures with different populations ranging from 5 * 10(1)
      to 5 * 10(8)  cfu/mL. It is found that the MSP-based biosensors work well in
      water and have a rapid response with a response time in minutes, which makes the
      MSP-based sensors suitable for in situ and real-time detection of pathogenic
      bacteria in liquid. The experimental results show that all MSP-phage and MSP
      antibody biosensors in size of 1.0 mm * 0.3 mm * 15 um exhibit a detection limit
      better than 100 cfu/mL. Based on the Hill plot, it is concluded that each
      bacterial cell is bound onto the sensor surface through about four-to-five sites.
      When the cultures with low population (<10(6)  cfu/mL) are tested, both MSP-phage
      and MSP-antibody sensors exhibit the similar response. However, the phage-MSP
      sensors exhibit a higher capability in the capture of target bacterial cell.

PMID- 24890795
TI  - Suicide in bipolar disorder: characteristics and subgroups.
AB  - OBJECTIVES: The development of more sophisticated models for understanding
      suicide among people with bipolar disorder (BD) requires diagnosis-specific data.
      The present study aimed to elucidate differences between people who die by
      suicide with and without BD, and to identify subgroups within those with BD.
      METHODS: Data on all suicide deaths in the city of Toronto from 1998 to 2010 were
      extracted from the Office of the Chief Coroner of Ontario, including
      demographics, clinical variables, recent stressors, and details of the suicide.
      Comparisons of person- and suicide-specific variables between suicide deaths
      among those with BD (n = 170) and those without (n = 2,716) were conducted, and a
      cluster analysis was performed among the BD suicide group only. RESULTS: Those in
      the BD suicide group were more likely than those in the non-BD suicide group to
      be female [odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.27-2.42; p =
      0.001], to have made a past suicide attempt (OR = 2.01, 95% CI: 1.45-2.80; p <
      0.0001), and to have had recent contact with psychiatric or emergency services
      (OR = 1.59, 95% CI: 1.00-2.52; p = 0.049). Five clusters were identified within
      the BD group, with differences between clusters in age; sex; marital status;
      living circumstances; past suicide attempts; substance abuse; interpersonal,
      employment/financial, and legal/police stressors; and rates of death by fall/jump
      or self-poisoning. CONCLUSIONS: The present findings identified differences
      between BD and non-BD suicide groups, providing support to the utilization of an
      illness-specific approach to better understanding suicide in BD. Subgroups of BD
      suicide deaths, if replicated, should also be incorporated into the design and
      analysis of future studies of suicide in BD.

PMID- 24890796
TI  - Factors perceived to influence exercise adherence in women with breast cancer
      participating in an exercise programme during adjuvant chemotherapy: a focus
      group study.
AB  - AIMS AND OBJECTIVES: To explore factors influencing exercise adherence among
      women with breast cancer while following an exercise programme. BACKGROUND:
      Earlier research shows that women with breast cancer decrease physical activity
      following the cancer diagnosis and that adhering to exercise interventions can be
      a challenge. Research is needed to identify motivational factors and barriers for
      exercise adherence among women during treatment for breast cancer. DESIGN: This
      was a qualitative study to explore patient's perceptions of the challenges to
      exercise adherence during a randomised, controlled trial. METHODS: Twenty-seven
      women with early-stage breast cancer were purposively sampled for focus group
      interviews during 2011-2012 from their participation in the exercise intervention
      group during 2010-2012. Five focus groups were performed, and data analysis was
      completed using the systematic text condensation method. RESULTS: During the
      focus group study, five main themes were identified, which described factors
      participants perceived to influence their adherence to exercise during
      chemotherapy: 'side effects of breast cancer treatment as a barrier to exercise',
      'restoring and maintaining normality in daily life motivates exercise', 'other
      valued activities compete with exercise', 'constructive support enhances
      exercise' and 'positive beliefs about efficacy and outcomes motivate exercise'.
      CONCLUSION: Adherence to exercise in women with breast cancer is challenged by
      internal and external conditions and may be improved by attention to the impact
      of treatment side effects and by supporting patient self-efficacy towards
      changing health behaviour. RELEVANCE TO CLINICAL PRACTICE: Nurses should be aware
      that exercise adherence could be a challenge among women with breast cancer. They
      should help identify obstacles to exercise for women and ways to overcome them,
      as well as support them in their beliefs that they are capable of changing their
      health behaviour.

PMID- 24890797
TI  - Intravenous iron in inflammatory bowel disease.

PMID- 24890799
TI  - Who pleads for the majority?

PMID- 24890798
TI  - Regulatory T-cell subsets with acquired functional impairment: important
      indicators of disease severity in atopic dermatitis.
AB  - Our aim was to assess whether the presence of highly active effector T cells in
      atopic dermatitis (AD) is associated with changes in the number and/or function
      of regulatory T cells (Tregs). Flow cytometry was utilised to determine the
      percentage of CD4+ CD25bright CD127-/low FOXP3+ and skin-homing CLA+ CD4+
      CD25bright FOXP3+ Tregs in healthy controls and AD patients. The correlation
      between disease severity and Treg percentages was estimated. Treg suppressor
      activity and cell proliferation were measured after T-cell stimulation.
      Significantly increased percentages of Tregs were found in AD patients compared
      to healthy individuals, and significant correlation between the frequency of
      Tregs and disease severity was also detected. The otherwise normal suppressor
      activity of Tregs decreased in the presence of Staphylococcus enterotoxin B
      (SEB). In conclusion, the continuous presence of SEB can trigger an acquired
      functional impairment of Tregs in AD patients and the correlation between the
      increased frequency of Tregs and disease severity supports their important role
      in AD pathogenesis.

PMID- 24890800
TI  - Giant esophageal gastrointestinal stromal tumor: report of a case.
AB  - Gastrointestinal stromal tumors (GISTs) rarely arise in the esophagus, where
      carcinoma is the most common malignant neoplasm and leiomyoma is the most common
      benign tumor. Because of their rarity, the clinical course and treatment of
      esophageal GISTs are poorly understood. These lesions are generally thought to
      carry a poor prognosis, making the differential diagnosis of other common
      mesenchymal neoplasms essential, for both prognostic and therapeutic reasons. We
      report a case of successfully resected giant esophageal GIST, thought to be the
      largest resected GIST reported in Japan. The patient was a 65-year-old woman, in
      whom upper gastrointestinal endoscopy found a 180-mm submucosal tumor in the
      lower thoracic esophagus, extending just below the aortic arch. We diagnosed
      esophageal GIST, and the patient underwent middle and lower esophagectomy via
      left thoracotomy, followed by gastric tube reconstruction. The tumor was resected
      completely. Histopathological and immunohistochemical staining confirmed that the
      tumor was a high-risk lesion, and treatment with imatinib was initiated. Computed
      tomography showed liver metastasis 5 months later, but the patient is doing well
      24 months after surgery.

PMID- 24890801
TI  - CYP3A4-dependent cellular response does not relate to CYP3A4-catalysed
      metabolites of C-1748 and C-1305 acridine antitumor agents in HepG2 cells.
AB  - High CYP3A4 expression sensitizes tumor cells to certain antitumor agents while
      for others it can lower their therapeutic efficacy. We have elucidated the
      influence of CYP3A4 overexpression on the cellular response induced by antitumor
      acridine derivatives, C-1305 and C-1748, in two hepatocellular carcinoma (HepG2)
      cell lines, Hep3A4 stably transfected with CYP3A4 isoenzyme, and HepC34
      expressing empty vector. The compounds were selected considering their different
      chemical structures and different metabolic pathways seen earlier in human and
      rat liver microsomes C-1748 was transformed to several metabolites at a higher
      rate in Hep3A4 than in HepC34 cells. In contrast, C-1305 metabolism in Hep3A4
      cells was unchanged compared to HepC34 cells, with each cell line producing a
      single metabolite of comparable concentration. C-1748 resulted in a progressive
      appearance of sub-G1 population to its high level in both cell lines. In turn,
      the sub-G1 fraction was dominated in CYP3A4-overexpressing cells following C-1305
      exposure. Both compounds induced necrosis and to a lesser extent apoptosis, which
      were more pronounced in Hep3A4 than in wild-type cells. In conclusion, CYP3A4
      overexpressing cells produce higher levels of C-1748 metabolites, but they do not
      affect the cellular responses to the drug. Conversely, cellular response was
      modulated following C-1305 treatment in CYP3A4-overexpressing cells, although
      metabolism of this drug was unaltered. 

PMID- 24890802
TI  - A supramolecular tubular nanoreactor.
AB  - The extremely strong noncovalent complexation between the rigid host of
      phthalocyanine-bridged beta-cyclodextrins and the amphiphilic guest carboxylated
      porphyrin is employed to construct a hollow tubular structure as a supramolecular
      nanoreactor. A representative coupling reaction occurs in the hydrophobic
      interlayers of the tubular walls in pure water at room temperature, leading to an
      enhancement of ten times higher reaction rate without any adverse effect on
      catalytic activity and conversion. 

PMID- 24890805
TI  - International Society of Urological Pathology grading and other prognostic
      factors for renal neoplasia.
AB  - The International Society of Urological Pathology convened an international
      consensus conference in 2012 to review aspects relating to the prognostic
      assessment, classification, and diagnosis of adult renal malignancy. The detailed
      recommendations of the conference are reported. 

PMID- 24890804
TI  - Validity of a self-administered food frequency questionnaire in the estimation of
      heterocyclic aromatic amines.
AB  - BACKGROUND: Clarification of the putative etiologic role of heterocyclic aromatic
      amines (HAAs) in the development of cancer requires a validated assessment tool
      for dietary HAAs. This study primarily aimed to evaluate the validity of a food
      frequency questionnaire (FFQ) in estimating HAA intake, using 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) level in human hair as the reference method.
      METHODS: We first updated analytical methods of PhIP using liquid chromatography
      electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) and measured 44
      fur samples from nine rats from a feeding study as part-verification of the
      quantitative performance of LC-ESI/MS/MS. We next measured PhIP level in human
      hair samples from a validation study of the FFQ (n = 65). HAA intake from the FFQ
      was estimated using information on intake from six fish items and seven meat
      items and data on HAA content in each food item. Correlation coefficients between
      PhIP level in human hair and HAA intake from the FFQ were calculated. RESULTS:
      The animal feeding study of PhIP found a significant dose-response relationship
      between dosage and PhIP in rat fur. Mean level was 53.8 pg/g hair among subjects
      with values over the limit of detection (LOD) (n = 57). We found significant
      positive correlation coefficients between PhIP in human hair and HAA intake from
      the FFQ, with Spearman rank correlation coefficients of 0.35 for all subjects,
      0.21 for subjects with over LOD values, and 0.34 for subjects with over limit of
      quantification. CONCLUSION: Findings from the validation study suggest that the
      FFQ is reasonably valid for the assessment of HAA intake.

PMID- 24890806
TI  - Optimal older adult emergency care: introducing multidisciplinary geriatric
      emergency department guidelines from the American College of Emergency
      Physicians, American Geriatrics Society, Emergency Nurses Association, and
      Society for Academic Emergency Medicine.
AB  - In the United States and around the world, effective, efficient, and reliable
      strategies to provide emergency care to aging adults is challenging crowded
      emergency departments (EDs) and strained healthcare systems. In response,
      geriatric emergency medicine clinicians, educators, and researchers collaborated
      with the American College of Emergency Physicians, American Geriatrics Society,
      Emergency Nurses Association, and Society for Academic Emergency Medicine to
      develop guidelines intended to improve ED geriatric care by enhancing expertise,
      educational, and quality improvement expectations, equipment, policies, and
      protocols. These Geriatric Emergency Department Guidelines represent the first
      formal society-led attempt to characterize the essential attributes of the
      geriatric ED and received formal approval from the boards of directors of each of
      the four societies in 2013 and 2014. This article is intended to introduce
      emergency medicine and geriatric healthcare providers to the guidelines while
      providing recommendations for continued refinement of these proposals through
      educational dissemination, formal effectiveness evaluations, cost-effectiveness
      studies, and eventually institutional credentialing. 

PMID- 24890803
TI  - A pooled multisite analysis of the effects of female reproductive hormones on
      glioma risk.
AB  - PURPOSE: The association between female reproductive factors and glioma risk is
      unclear, but most published studies have been limited by small sample size. We
      conducted a pooled multisite study of pre- and postmenopausal women,
      investigating the effect of female reproductive factors, including hormonal
      medications. METHODS: Unconditional logistic regression was used to calculate
      odds ratios (ORs) and 95 % confidence intervals (95 % CIs) assessing the effects
      of female reproductive factors and female hormonal medications in glioma cases
      and unrelated controls. RESULTS: Menarche over the age of 15 as compared to under
      12 was associated with a statistically significant risk for glioma (OR 2.00, 95 %
      CI 1.47-2.71). Use of oral contraceptive pills (OCP) was inversely associated
      with risk of glioma (OR 0.61, 95 % CI 0.50-0.74), and there was an inverse trend
      with longer duration of OCP use (p for trend <0.0001). Use of hormone replacement
      therapy (HRT) was also inversely associated with risk of glioma (OR 0.55, 95 % CI
      0.44-0.68), and there was an inverse trend with longer duration of use (p for
      trend <0.0001). Compared to those reporting neither OCP use nor HRT use, those
      who reported using both were less likely to have a diagnosis of glioma (OR 0.34,
      95 % CI 0.24-0.48). CONCLUSIONS: Female reproductive hormones may decrease the
      risk for glioma. The association appears to be strongest with greater length of
      use and use of both HRT and OCP.

PMID- 24890807
TI  - Construction of breast cancer gene regulatory networks and drug target
      optimization.
AB  - OBJECTIVE: The purpose of this study was to construct the breast cancer gene
      regulatory networks through the high-throughput techniques and optimize the drug
      target genes of breast cancer using bioinformatics analysis, and thus accelerate
      the process of drug development and improve the cure rate of breast cancer.
      METHODS: The gene expression profile data of breast cancer were downloaded from
      GEO database and the transcriptional regulation data were obtained from UCSC
      database. Then we identified the differentially expressed genes (DEGs) by SAM
      algorithm and built gene regulatory networks by the supervised algorithm SIRENE.
      Finally, the drug targets of the DEGs with changed regulation relations were
      optimized based on the CancerResource database. RESULTS: A total of 584 DEGs were
      identified and the gene regulatory networks in the normal state and tumorous
      state were constructed. By comparing the new predicted regulatory relation in
      cancer state and normal state, the regulatory relation of 18 genes was found to
      be changed in the two states, showing the possibility to be applied as drug
      target genes. After the searches in the CancerResources, 7 genes were screened as
      the drug target genes, such as PFKFB3. CONCLUSION: Our present findings shed new
      light on the molecular mechanism of breast cancer and provide some drug targets
      which have the potential to be used in clinic for the treatment of breast cancer
      in future.

PMID- 24890808
TI  - Reference ranges of myocardial performance index from 12 to 40 weeks of
      gestation.
AB  - OBJECTIVE: To establish reference ranges of fetal myocardial performance index
      (MPI) in normal singleton pregnancies from 12 to 40 weeks gestation. DESIGN:
      Prospective descriptive study. SETTING: A tertiary care teaching center in the
      Northern part of Thailand. PARTICIPANTS: A total of 562 normal singleton
      pregnancies at 12-40 weeks of gestation. INTERVENTION: Fetal echocardiography was
      performed for isovolumetric contraction time, isovolumetric relaxation time,
      ejection time and MPI by one experienced sonographer, using strict criteria for
      measurement. The measured MPI values were regressed against gestational age (GA)
      and biparietal diameter (BPD) to determine the best-fitted model. PRIMARY OUTCOME
      MEASURES: MPI for each gestational week and each BPD point (cm). RESULTS: A total
      of 562 measurements were successfully obtained with good-quality Doppler tracings
      and complete data for analysis. Predicted mean of MPI for GA and BPD is as
      follows: predicted mean MPI = 0.404 + 0.004 * GA (weeks) (r (2) = 0.143, p <
      0.001) and = 0.419 + 0.015 * BPD (cm) (r (2) = 0.139, p < 0.001) as functions of
      GA and BPD, respectively. The predicted SD of MPI for GA and BPD is constant
      throughout pregnancy, 0.071348 and 0.073440, respectively. CONCLUSION: MPI is
      significantly increased with GA. The reference ranges of MPI according to GA and
      BPD, as a marker in evaluating global cardiac function between 12 and 40 weeks of
      gestation was constructed.

PMID- 24890810
TI  - A rare cause of florid, haemorrhagic blisters in two siblings.

PMID- 24890809
TI  - Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte
      cytotoxicity via a tyrosinase-dependent mechanism.
AB  - Rhododendrol, an inhibitor of melanin synthesis developed for
      lightening/whitening cosmetics, was recently reported to induce a depigmentary
      disorder principally at the sites of repeated chemical contact. Rhododendrol
      competitively inhibited mushroom tyrosinase and served as a good substrate, while
      it also showed cytotoxicity against cultured human melanocytes at high
      concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was
      abolished by phenylthiourea, a chelator of the copper ions at the active site,
      and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity
      appeared to be triggered by the enzymatic conversion of rhododendrol to active
      product(s). No reactive oxygen species were detected in the treated melanocytes,
      but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene
      responsible for apoptosis and/or autophagy and caspase-3 activation were found to
      be tyrosinase dependent. These results suggest that a tyrosinase-dependent
      accumulation of ER stress and/or activation of the apoptotic pathway may
      contribute to the melanocyte cytotoxicity. 

PMID- 24890811
TI  - Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through
      the mTOR-STAT3/microRNA143 pathway.
AB  - Cancer cells preferentially metabolize glucose through aerobic glycolysis, a
      phenomenon known as the Warburg effect. Emerging evidence has shown that long non
      coding RNAs (lncRNAs) act as key regulators of multiple cancers. However, it
      remains largely unexplored whether and how lncRNA regulates glucose metabolism in
      cancer cells. In this study, we show that lncRNA UCA1 promotes glycolysis in
      bladder cancer cells, and that UCA1-induced hexokinase 2 (HK2) functions as an
      important mediator in this process. We further show that UCA1 activates mTOR to
      regulate HK2 through both activation of STAT3 and repression of microRNA143.
      Taken together, these findings provide the first evidence that UCA1 plays a
      positive role in cancer cell glucose metabolism through the cascade of mTOR
      STAT3/microRNA143-HK2, and reveal a novel link between lncRNA and the altered
      glucose metabolism in cancer cells. 

PMID- 24890812
TI  - Lymphangiogenesis: implications for diagnosis, treatment, and prognosis in
      patients with melanoma.
AB  - Disease course in melanoma often cannot be accurately predicted by means of the
      prognostic factors usually considered in patients with melanoma; therefore, new
      factors are clearly needed. Increasingly robust scientific evidence shows that
      tumor lymph vessels play a key role in melanoma that metastasizes by lymphatic
      and hematogenous pathways. We review current knowledge and examine the
      implications of lymphangiogenesis in the diagnosis, treatment, and prognosis of
      patients with melanoma. 

PMID- 24890813
TI  - Asymptomatic nodule on the leg.

PMID- 24890814
TI  - Shark island flap for reconstruction of nasal ala-perinasal defects.

PMID- 24890816
TI  - Procoagulant abnormalities in cirrhosis with portal vein thrombosis.

PMID- 24890815
TI  - MicroRNA-26b inhibits epithelial-mesenchymal transition in hepatocellular
      carcinoma by targeting USP9X.
AB  - BACKGROUND: Metastasis is responsible for the rapid recurrence and poor survival
      of malignancies. Epithelial-mesenchymal transition (EMT) has a critical role in
      metastasis. Increasing evidence indicates that EMT can be regulated by microRNAs
      (miRNAs). The aim of this study was to investigate the role of miR-26b in
      modulating epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma
      (HCC), as well as to identify its underlying mechanism of action. METHODS: The
      expression level of miR-26b was assessed in multiple HCC cell lines (HepG2,
      MHCC97H, Hep3B, MHCC97L, HCCC9810, BEL-7402, Huh7 and QGY-7703), as well as in
      liver tissue from patients with HCC. Follow-up studies examined the effects of a
      miR-26b mimic (increased expression) and a miR-26b inhibitor (decreased
      expression) on markers of EMT, wound healing and cell migration. The molecular
      target of miR-26b was also identified using a computer algorithm and confirmed
      experimentally. RESULTS: MiR-26b expression was decreased in HCC cell lines and
      was inversely correlated with the grade of HCC. Increased expression of miR-26b
      inhibited the migration and invasiveness of HCC cell lines, which was accompanied
      by decreased expression of the epithelial marker E-cadherin and increased
      expression of the mesenchymal marker vimentin, at both the mRNA and protein
      expression levels. A binding site for miR-26b was theoretically identified in the
      3'UTR of USP9X. Further studies revealed that overexpression of miR-26b repressed
      the endogenous level of USP9X protein expression. Overexpression of miR-26b also
      repressed Smad4 expression, whereas its inhibition elevated Smad4 expression.
      CONCLUSIONS: Taken together, our results indicate that miR-26b were inhibited in
      HCC. In HCC cell lines, miR-26b targeted the 3'UTR of USP9X, which in turn
      affects EMT through Smad4 and the TGF-beta signaling pathway. Our analysis of
      clinical HCC samples verifies that miR-26b also targets USP9X expression to
      inhibit the EMT of hepatocytes. Thus, miR-26b may have some effects on the EMT of
      HCC cells.

PMID- 24890817
TI  - Cyclodextrin-mediated enantioseparation of phenylalanine amide derivatives and
      amino alcohols by capillary electrophoresis-role of complexation constants and
      complex mobilities.
AB  - The separation of the enantiomers of phenylalanine amide and N-methyl derivatives
      as well as some amino alcohols was studied by CE in acidic BGEs using CDs as
      chiral selectors. The native CDs displayed only low chiral recognition ability at
      a concentration of 15 mg/mL in 20 mM sodium phosphate buffer, pH 2.5. In
      contrast, the analyte enantiomers were separated in the presence of randomly
      sulfated CDs under reversed polarity of the applied voltage. Sulfated beta-CD
      proved to be the most universal selector resulting in the enantioseparation of
      all analytes. Opposite enantiomer migration order depending on the size of the CD
      cavity was observed for phenylalanine amide and 2-amino-2-phenylethanol. The R
      enantiomers migrated first in the presence of sulfated alpha-CD and gamma-CD
      while the S-enantiomers were detected first in the presence of sulfated beta-CD.
      The enantioseparations could be rationalized based on analyte complexation by the
      respective CDs except for 2-amino-2-phenylethanol and sulfated beta-CD where
      essentially equal complexation constants were derived for the enantiomers. In
      this case, the migration behavior could be attributed to the mobilities of the
      enantiomer-CD complexes adding another example to the CE-specific phenomenon of
      enantioseparations based primarily on complex mobilities. 

PMID- 24890818
TI  - A seroprevalence study of primate workers for asymptomatic rhesus cytomegalovirus
      infection.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection can cause severe disease in
      neonates and immunocompromised persons, and infectious mononucleosis in healthy
      adults. While, rhesus CMV (RhCMV) infects human cells in culture, it is unknown
      whether the virus can infect humans. OBJECTIVES: We sought to determine whether
      primate workers, including those with injuries from animals, might be infected
      asymptomatically with RhCMV. STUDY DESIGN: We developed serologic assays that
      distinguish RhCMV from HCMV antibodies. We tested two groups of primate workers:
      those with documented injuries or mucosal splashes associated with rhesus
      macaques, and those with no documented exposure who worked with these animals.
      RESULTS: None of over 200 primate workers, including 119 with injuries or mucosal
      splashes associated with exposures to macaques, were seropositive for RhCMV.
      CONCLUSIONS: The frequency of asymptomatic RhCMV infection in persons who work
      with rhesus macaques was <0.5% (<1/200 primate workers).

PMID- 24890819
TI  - Hepatitis B virus DNA quantification with the three-in-one (3io) method allows
      accurate single-step differentiation of total HBV DNA and cccDNA in biopsy-size
      liver samples.
AB  - BACKGROUND: Hepatitis B virus (HBV) replicates via reverse transcription
      converting its partially double stranded genome into the covalently closed
      circular DNA (cccDNA). The long-lasting cccDNA serves as a replication
      intermediate in the nuclei of hepatocytes. It is an excellent, though evasive,
      parameter for monitoring the course of liver disease and treatment efficiency.
      OBJECTIVE: To develop and test a new approach for HBV DNA quantification in serum
      and small-size liver samples. STUDY DESIGN: The p3io plasmid contains an HBV
      fragment and human beta-actin gene (hACTB) as a standard. Respective TaqMan
      probes were labeled with different fluorescent dyes. A triplex real-time PCR for
      simultaneous quantification of total HBV DNA, cccDNA and hACTB could be
      established. RESULTS: Three-in-one method allows simultaneous analysis of 3
      targets with a lower limit of quantification of 48 copies per 20 MUl PCR reaction
      and a wide range of linearity (R(2)>0.99, p<0.0001) for all measured sequences.
      The method showed a pan-genotypic specificity among genotypes A-F with serum DNA
      samples from HBV infected patients. Total HBV DNA and cccDNA could be quantified
      in 32 and 22 of 33 FFPE preserved liver specimens, respectively. Total HBV DNA
      concentrations quantified by the 3io method remained comparable with Cobas TaqMan
      HBV Test v2.0. CONCLUSIONS: The three-in-one protocol allows the single step
      quantification of viral DNA in samples from different sources. Therefore lower
      sample input, faster data acquisition, a lowered error and significantly lower
      costs are the advantages of the method.

PMID- 24890820
TI  - Biophysical and biomechanical properties of myofilament proteins.

PMID- 24890821
TI  - Association of dental caries with socioeconomic status in relation to different
      water fluoridation levels.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of dental caries
      in 11-year-old children, related to water fluoridation and family affluence scale
      (FAS), as an indicator of socioeconomic status (SES) in Korea. METHODS: A total
      of eight areas were selected for study: four areas with fluoridated piped water
      (WF areas) and four areas with nonfluoridated piped water (non-WF areas). Non-WF
      areas had a similar economic level and population size compared with the WF
      areas. A total of 1446 elementary school students, 11 years of age, were
      included. They were examined, and questionnaires completed by their parents were
      analyzed. In the questionnaire, information about gender, FAS as an indicator of
      SES, occasions of daily cariogenic snack intake, occasions of daily cariogenic
      beverage intake, drinking of piped water, cooking with piped water, and usage of
      oral hygiene supplemental measures were surveyed. The bivariate association
      between the characteristics of the subjects and the number of decayed, filled,
      and missing permanent teeth (DMFT score) was analyzed through an independent
      samples t-test. The difference in the mean DMFT score between different FAS
      groups was analyzed by DMFT ratio, after adjusting for gender, oral health
      behaviors, and usage of piped water variables. The DMFT ratio was calculated from
      a Poisson regression model, because the DMFT score was not normally distributed.
      RESULTS: There was no significant association between FAS and the mean DMFT score
      in both areas, by bivariate analysis. After adjusting for each group of
      confounders, a significant association (95% CI: 1.032-1.513) was found between
      the FAS and mean DMFT scores in non-WF areas; however, no significant difference
      was observed in the WF areas (95% CI: 0.766-1.382). CONCLUSIONS: This study
      supported that water fluoridation could not only lead to a lower prevalence of
      dental caries, but also help to reduce the effect of SES inequalities on oral
      health.

PMID- 24890823
TI  - Diurnal variation in blood pressure and arterial stiffness in chronic kidney
      disease: the role of endothelin-1.
AB  - Hypertension and arterial stiffness are important independent cardiovascular risk
      factors in chronic kidney disease (CKD) to which endothelin-1 (ET-1) contributes.
      Loss of nocturnal blood pressure (BP) dipping is associated with CKD progression,
      but there are no data on 24-hour arterial stiffness variation. We examined the 24
      hour variation of BP, arterial stiffness, and the ET system in healthy volunteers
      and patients with CKD and the effects on these of ET receptor type A receptor
      antagonism (sitaxentan). There were nocturnal dips in systolic BP and diastolic
      BP and pulse wave velocity, our measure of arterial stiffness, in 15 controls
      (systolic BP, -3.2+/-4.8%, P<0.05; diastolic BP, -6.4+/-6.2%, P=0.001; pulse wave
      velocity, -5.8+/-5.2%, P<0.01) but not in 15 patients with CKD. In CKD, plasma ET
      1 increased by 1.2+/-1.4 pg/mL from midday to midnight compared with healthy
      volunteers (P<0.05). Urinary ET-1 did not change. In a randomized, double-blind,
      3-way crossover study in 27 patients with CKD, 6-week treatment with placebo and
      nifedipine did not affect nocturnal dips in systolic BP or diastolic BP between
      baseline and week 6, whereas dipping was increased after 6-week sitaxentan
      treatment (baseline versus week 6, systolic BP: -7.0+/-6.2 versus -11.0+/-7.8 mm
      Hg, P<0.05; diastolic BP: -6.0+/-3.6 versus -8.3+/-5.1 mm Hg, P<0.05). There was
      no nocturnal dip in pulse pressure at baseline in the 3 phases of the study,
      whereas sitaxentan was linked to the development of a nocturnal dip in pulse
      pressure. In CKD, activation of the ET system seems to contribute not only to
      raised BP but also the loss of BP dipping. The clinical significance of these
      findings should be explored in future clinical trials.

PMID- 24890822
TI  - Sex differences in T-lymphocyte tissue infiltration and development of
      angiotensin II hypertension.
AB  - There is extensive evidence that activation of the immune system is both
      necessary and required for the development of angiotensin II (Ang II)-induced
      hypertension in males. The purpose of this study was to determine whether sex
      differences exist in the ability of the adaptive immune system to induce Ang II
      dependent hypertension and whether central and renal T-cell infiltration during
      Ang II-induced hypertension is sex dependent. Recombinant activating gene-1 (Rag
      1)(-/-) mice, lacking both T and B cells, were used. Male and female Rag-1(-/-)
      mice received adoptive transfer of male CD3(+) T cells 3 weeks before 14-day Ang
      II infusion (490 ng/kg per minute). Blood pressure was monitored via tail cuff.
      In the absence of T cells, systolic blood pressure responses to Ang II were
      similar between sexes (Delta22.1 mm Hg males versus Delta18 mm : Hg females).
      After adoptive transfer of male T cells, Ang II significantly increased systolic
      blood pressure in males (Delta37.7 mm : Hg; P<0.05) when compared with females
      (Delta13.7 mm : Hg). Flow cytometric analysis of total T cells and CD4(+),
      CD8(+), and regulatory Foxp3(+)-CD4(+) T-cell subsets identified that renal
      lymphocyte infiltration was significantly increased in males versus females in
      both control and Ang II-infused animals (P<0.05). Immunohistochemical staining
      for CD3(+)-positive T cells in the subfornical organ region of the brain was
      increased in males when compared with that in females. These results suggest that
      female Rag-1(-/-) mice are protected from male T-cell-mediated increases in Ang
      II-induced hypertension when compared with their male counterparts, and this
      protection may involve sex differences in the magnitude of T-cell infiltration of
      the kidney and brain. 

PMID- 24890824
TI  - Transient receptor potential vanilloid 1 activation by dietary capsaicin promotes
      urinary sodium excretion by inhibiting epithelial sodium channel alpha subunit
      mediated sodium reabsorption.
AB  - High salt (HS) intake contributes to the development of hypertension. Epithelial
      sodium channels play crucial roles in regulating renal sodium reabsorption and
      blood pressure. The renal transient receptor potential vanilloid 1 (TRPV1) cation
      channel can be activated by its agonist capsaicin. However, it is unknown whether
      dietary factors can act on urinary sodium excretion and renal epithelial sodium
      channel (ENaC) function. Here, we report that TRPV1 activation by dietary
      capsaicin increased urinary sodium excretion through reducing sodium reabsorption
      in wild-type (WT) mice on a HS diet but not in TRPV1(-/-) mice. The effect of
      capsaicin on urinary sodium excretion was involved in inhibiting alphaENaC and
      its related with-no-lysine kinase 1/serum- and glucocorticoid-inducible protein
      kinase 1 pathway in renal cortical collecting ducts of WT mice. Dietary capsaicin
      further reduced the increased alphaENaC activity in WT mice attributed to the HS
      diet. In contrast, this capsaicin effect was absent in TRPV1(-/-) mice.
      Immunoprecipitation study indicated alphaENaC specifically coexpressed and
      functionally interact with TRPV1 in renal cortical collecting ducts of WT mice.
      Additionally, ENaC activity and expression were suppressed by capsaicin-mediated
      TRPV1 activation in cultured M1-cortical collecting duct cells. Long-term dietary
      capsaicin prevented the development of high blood pressure in WT mice on a HS
      diet. It concludes that TRPV1 activation in the cortical collecting ducts by
      capsaicin increases urinary sodium excretion and avoids HS diet-induced
      hypertension through antagonizing alphaENaC-mediated urinary sodium reabsorption.
      Dietary capsaicin may represent a promising lifestyle intervention in populations
      exposed to a high dietary salt intake. 

PMID- 24890825
TI  - Sex differences in blood pressure control: are T lymphocytes the missing link?

PMID- 24890826
TI  - Reliability and validity of a survey to measure bowel function and quality of
      life in long-term rectal cancer survivors.
AB  - PURPOSE: Examination of reliability and validity of a specialized health-related
      quality of life questionnaire for rectal cancer (RC) survivors (>=5 years post
      diagnosis). METHODS: We mailed 1,063 Kaiser Permanente (KP) RC survivors (313
      ostomy and 750 anastomosis) a questionnaire containing the Modified City of Hope
      Quality of Life-Ostomy (mCOH-QOL-O), SF-12v2, Duke-UNC Functional Social Support
      Questionnaire (FSSQ), and Memorial Sloan-Kettering Cancer Center Bowel Function
      Index (BFI). We adapted certain BFI items for use by subjects with intestinal
      ostomies. We evaluated reliability for all instruments with inter-item
      correlations and Cronbach's alpha. We assessed construct validity only for the
      BFI in the ostomy group, because such use has not been reported. RESULTS: The
      overall response rate was 60.5 % (577 respondents/953 eligible). Compared with
      non-responders, participants were on average 2 years younger and more likely non
      Hispanic white, resided in educationally non-deprived areas, and had KP
      membership through a group. The mCOH-QOL-O, SF-12, and FSSQ were found to be
      highly reliable for RC survivors. In the ostomy group, BFI Urgency/Soilage and
      Dietary subscales were found to be reliable, but Frequency was not. Factor
      analysis supported the construct of Urgency/Soilage and Dietary subscales in the
      ostomy group, although one item had a moderate correlation with all three
      factors. The BFI also demonstrated good concurrent validity with other
      instruments in the ostomy group. CONCLUSIONS: With possible exception of the BFI
      Frequency subscale in populations with ostomies, components of our survey can be
      used for the entire population of RC survivors, no matter whether they received
      anastomosis or ostomy.

PMID- 24890827
TI  - Assessing the validity of single-item life satisfaction measures: results from
      three large samples.
AB  - PURPOSE: The present paper assessed the validity of single-item life satisfaction
      measures by comparing single-item measures to the Satisfaction with Life Scale
      (SWLS)-a more psychometrically established measure. METHODS: Two large samples
      from Washington (N = 13,064) and Oregon (N = 2,277) recruited by the Behavioral
      Risk Factor Surveillance System and a representative German sample (N = 1,312)
      recruited by the Germany Socio-Economic Panel were included in the present
      analyses. Single-item life satisfaction measures and the SWLS were correlated
      with theoretically relevant variables, such as demographics, subjective health,
      domain satisfaction, and affect. The correlations between the two life
      satisfaction measures and these variables were examined to assess the construct
      validity of single-item life satisfaction measures. RESULTS: Consistent across
      three samples, single-item life satisfaction measures demonstrated substantial
      degree of criterion validity with the SWLS (zero-order r = 0.62-0.64;
      disattenuated r = 0.78-0.80). Patterns of statistical significance for
      correlations with theoretically relevant variables were the same across single
      item measures and the SWLS. Single-item measures did not produce systematically
      different correlations compared to the SWLS (average difference = 0.001-0.005).
      The average absolute difference in the magnitudes of the correlations produced by
      single-item measures and the SWLS was very small (average absolute difference =
      0.015-0.042). CONCLUSIONS: Single-item life satisfaction measures performed very
      similarly compared to the multiple-item SWLS. Social scientists would get
      virtually identical answer to substantive questions regardless of which measure
      they use.

PMID- 24890828
TI  - The characteristics and relevant factors of Pap smear test use for women with
      intellectual disabilities in Taiwan.
AB  - BACKGROUND: This study examines the Pap smear usage conditions and relevant
      influential factors for 18,204 women aged 30 years and above with intellectual
      disabilities, using nationwide data from 2008. METHODS: The research method of
      this study is secondary data analysis. The data was obtained from three
      nationwide databases from 2006 to 2008. This study employed descriptive
      statistics to analyze the use and rate of Pap smear testing by women with
      intellectual disabilities. Chi-square test was used to assess the correlation
      between Pap smear test usage and several variables. Logistic regression analysis
      was employed to explore the factors that influence Pap smear test usage. RESULTS:
      The results show that 4.83% (n =880) of women with intellectual disabilities
      underwent Pap smear tests. Pap smear test usage rates exhibit a declining trend
      with increases in age. Factors that significantly influence Pap smear test use
      include age, urbanization level of resident area, monthly salary, aboriginal
      status, marital status, existence of DM, severity of disability. CONCLUSIONS: The
      women with intellectual disabilities had a low use rate of Pap smear test, which
      is significantly less than the 28.8% usage rate for the general population of
      women aged 30 years and above.

PMID- 24890829
TI  - Genomovar assignment of Pseudomonas stutzeri populations inhabiting produced oil
      reservoirs.
AB  - Oil reservoirs are specific habitats for the survival and growth of
      microorganisms in general. Pseudomonas stutzeri which is believed to be an
      exogenous organism inoculated into oil reservoirs during the process of oil
      production was detected frequently in samples from oil reservoirs. Very little is
      known, however, about the distribution and genetic structure of P. stutzeri in
      the special environment of oil reservoirs. In this study, we collected 59 P.
      stutzeri 16S rRNA gene sequences that were identified in 42 samples from 25
      different oil reservoirs and we isolated 11 cultured strains from two
      representative oil reservoirs aiming to analyze the diversity and genomovar
      assignment of the species in oil reservoirs. High diversity of P. stutzeri was
      observed, which was exemplified in the detection of sequences assigned to four
      known genomovars 1, 2, 3, 20 and eight unknown genomic groups of P. stutzeri. The
      frequent detection and predominance of strains belonging to genomovar 1 in most
      of the oil reservoirs under study indicated an association of genomovars of P.
      stutzeri with the oil field environments. 

PMID- 24890831
TI  - Cardiovascular drug discovery: a perspective from a research-based pharmaceutical
      company.
AB  - The theme of this review is to summarize the evolving processes in cardiovascular
      drug discovery and development within a large pharmaceutical company. Emphasis is
      placed on the contrast between the academic and industrial research operating
      environments, which can influence the effectiveness of research collaboration
      between the two constituencies, but which plays such an important role in drug
      innovation. The strategic challenges that research directors face are also
      emphasized. The need for improved therapy in many cardiovascular indications
      remains high, but the feasibility in making progress, despite the advances in
      molecular biology and genomics, is also assessed.

PMID- 24890830
TI  - Diversification and specialization of touch receptors in skin.
AB  - Our skin is the furthest outpost of the nervous system and a primary sensor for
      harmful and innocuous external stimuli. As a multifunctional sensory organ, the
      skin manifests a diverse and highly specialized array of mechanosensitive neurons
      with complex terminals, or end organs, which are able to discriminate different
      sensory stimuli and encode this information for appropriate central processing.
      Historically, the basis for this diversity of sensory specializations has been
      poorly understood. In addition, the relationship between cutaneous mechanosensory
      afferents and resident skin cells, including keratinocytes, Merkel cells, and
      Schwann cells, during the development and function of tactile receptors has been
      poorly defined. In this article, we will discuss conserved tactile end organs in
      the epidermis and hair follicles, with a focus on recent advances in our
      understanding that have emerged from studies of mouse hairy skin.

PMID- 24890835
TI  - Clinical characteristics and current treatment of glaucoma.
AB  - Glaucoma is a neurodegenerative disorder in which degenerating retinal ganglion
      cells (RGC) produce significant visual disability. Clinically, glaucoma refers to
      an array of conditions associated with variably elevated intraocular pressure
      (IOP) that contributes to RGC loss via mechanical stress, vascular abnormalities,
      and other mechanisms, such as immune phenomena. The clinical diagnosis of
      glaucoma requires assessment of the ocular anterior segment with slit lamp
      biomicroscopy, which allows the clinician to recognize signs of conditions that
      can produce elevated IOP. After measurement of IOP, a specialized prismatic lens
      called a gonioscope is used to determine whether the angle is physically open or
      closed. The structural manifestation of RGC loss is optic nerve head atrophy and
      excavation of the neuroretinal rim tissue. Treatment is guided by addressing
      secondary causes for elevated IOP (such as inflammation, infection, and ischemia)
      whenever possible. Subsequently, a variety of medical, laser, and surgical
      options are used to achieve a target IOP.

PMID- 24890834
TI  - Cell therapy in dermatology.
AB  - Harnessing the regenerative capacity of keratinocytes and fibroblasts from human
      skin has created new opportunities to develop cell-based therapies for patients.
      Cultured cells and bioengineered skin products are being used to treat patients
      with inherited and acquired skin disorders associated with defective skin, and
      further clinical trials of new products are in progress. The capacity of
      extracutaneous sources of cells such as bone marrow is also being investigated
      for its plasticity in regenerating skin, and new strategies, such as the
      derivation of inducible pluripotent stem cells, also hold great promise for
      future cell therapies in dermatology. This article reviews some of the
      preclinical and clinical studies and future directions relating to cell therapy
      in dermatology, particularly for inherited skin diseases associated with fragile
      skin and poor wound healing.

PMID- 24890832
TI  - MYC activation is a hallmark of cancer initiation and maintenance.
AB  - The MYC proto-oncogene has been implicated in the pathogenesis of most types of
      human tumors. MYC activation alone in many normal cells is restrained from
      causing tumorigenesis through multiple genetic and epigenetically controlled
      checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular
      senescence. When pathologically activated in a permissive epigenetic and/or
      genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark"
      features of cancer, including relentless tumor growth associated with DNA
      replication and transcription, cellular proliferation and growth, protein
      synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by
      inducing stemness and blocking cellular senescence and differentiation.
      Additionally, MYC orchestrates changes in the tumor microenvironment, including
      the activation of angiogenesis and suppression of the host immune response.
      Provocatively, brief or even partial suppression of MYC back to its physiological
      levels of activation can result in the restoration of intrinsic checkpoint
      mechanisms, resulting in acute and sustained tumor regression, associated with
      tumor cells undergoing proliferative arrest, differentiation, senescence, and
      apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an
      immune response, and shutdown of angiogenesis. Hence, tumors appear to be
      "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host
      dependent, immune cell-dependent mechanisms. Both the trajectory and persistence
      of many human cancers require sustained MYC activation. Multiscale mathematical
      modeling may be useful to predict when tumors will be addicted to MYC. MYC is a
      hallmark molecular feature of both the initiation and maintenance of
      tumorigenesis.

PMID- 24890833
TI  - MYC and the control of DNA replication.
AB  - The MYC oncogene is a multifunctional protein that is aberrantly expressed in a
      significant fraction of tumors from diverse tissue origins. Because of its
      multifunctional nature, it has been difficult to delineate the exact
      contributions of MYC's diverse roles to tumorigenesis. Here, we review the normal
      role of MYC in regulating DNA replication as well as its ability to generate DNA
      replication stress when overexpressed. Finally, we discuss the possible
      mechanisms by which replication stress induced by aberrant MYC expression could
      contribute to genomic instability and cancer.

PMID- 24890838
TI  - A comprehensive approach to the determination of two benzimidazoles in
      environmental samples.
AB  - Among the various pharmaceuticals regarded as emerging pollutants, benzimidazoles
      -represented by flubendazole and fenbendazole--are of particular concern because
      of their large-scale use in veterinary medicine and their health effects on
      aquatic organisms. For this reason, it is essential to have reliable analytical
      methods which can be used to simultaneously monitor their appearance in
      environmental matrices such as water, sediment and tissue samples. To date,
      however, such methods relating to these three matrices have not been available.
      In this paper we present a comprehensive approach to the determination of both
      drugs in the mentioned above matrices using liquid chromatography-ion trap mass
      spectrometry (LC-MS/MS). Special attention was paid to the sample preparation
      step. The optimal extraction methods were further validated by experiments with
      spiked water, sediment and fish tissue samples. Matrix effects were established.
      The following absolute recoveries of flubendazole and fenbendazole were achieved:
      96.2% and 95.4% from waters, 103.4% and 98.3% from sediments, and 98.3% and 97.6%
      from fish tissue samples, respectively. Validation of the LC-MS/MS methods enable
      flubendazole and fenbendazole to be determined with method detection limits: 1.6
      ng L(-1) and 1.7 ng L(-1) in water samples; 0.3 ng g(-1) for both compounds in
      sediment samples, and 3.3 ng g(-1) and 3.5 ng g(-1) in tissue samples,
      respectively. The proposed methods were successfully used for analysing selected
      pharmaceuticals in real samples collected in northern Poland. There is first data
      on the concentration in the environment of the target compounds in Poland.

PMID- 24890839
TI  - Occurrence and spatial distribution of emerging contaminants in the unsaturated
      zone. case study: Guadalete River basin (Cadiz, Spain).
AB  - Irrigation with reclaimed water is becoming a common practice in arid- and semi
      arid regions as a consequence of structural water resource scarcity. This
      practice can lead to contamination of the vadose zone if sewage-derived
      contaminants are not removed properly. In the current work, we have characterized
      soils from the Guadalete River basin (SW Spain), which are often irrigated with
      reclaimed water from a nearby wastewater treatment plant and amended using
      sludge. Physico-chemical, mineralogical and hydraulic properties were measured in
      soil samples from this area (from surface up to 2 m depth). Emerging contaminants
      (synthetic surfactants and pharmaceutically active compounds, or PhACs) were also
      determined. Synthetic surfactants, widely used in personal care products (PCPs),
      were found in a wide range of concentrations: 73-1300 MUg kg(-1) for linear
      alkylbenzene sulfonates (LAS), 120-496 MUg kg(-1) for alkyl ethoxysulfates (AES),
      19-1090 MUg kg(-1) for alcohol polyethoxylates (AEOs), and 155-280 MUg kg(-1) for
      nonylphenol polyethoxylates (NPEOs). The presence of surfactant homologues with
      longer alkyl chains was predominant due to their sorption capacity. A positive
      correlation was found between LAS and AEOs and soil organic carbon and clay
      content, respectively. Out of 64 PhACs analyzed, only 7 were detected
      occasionally (diclofenac, metoprolol, fenofibrate, carbamazepine, clarithromycin,
      famotidine and hydrochlorothiazide), always at very low concentrations (from 0.1
      to 1.3 MUg kg(-1)).

PMID- 24890837
TI  - Mendelian genetics of human susceptibility to fungal infection.
AB  - A recent surge in newly described inborn errors of immune function-related genes
      that result in susceptibility to fungal disease has greatly enhanced our
      understanding of the cellular and molecular basis of antifungal immune responses.
      Characterization of single-gene defects that predispose to various combinations
      of superficial and deep-seated infections caused by yeasts, molds, and dimorphic
      fungi has unmasked the critical role of novel molecules and signaling pathways in
      mucosal and systemic antifungal host defense. These experiments of nature offer a
      unique opportunity for developing new knowledge in immunological research and
      form the foundation for devising immune-based therapeutic approaches for patients
      infected with fungal pathogens. 

PMID- 24890841
TI  - Does relaxed predation drive phenotypic divergence among insular populations?
AB  - The evolution of striking phenotypes on islands is a well-known phenomenon, and
      there has been a long-standing debate on the patterns of body size evolution on
      islands. The ecological causes driving divergence in insular populations are,
      however, poorly understood. Reduced predator fauna is expected to lower escape
      propensity, increase body size and relax selection for crypsis in small-bodied,
      insular prey species. Here, we investigated whether escape behaviour, body size
      and dorsal coloration have diverged as predicted under predation release in
      spatially replicated islet and mainland populations of the lizard species
      Podarcis gaigeae. We show that islet lizards escape approaching observers at
      shorter distances and are larger than mainland lizards. Additionally, we found
      evidence for larger between-population variation in body size among the islet
      populations than mainland populations. Moreover, islet populations are
      significantly more divergent in dorsal coloration and match their respective
      habitats poorer than mainland lizards. These results strongly suggest that
      predation release on islets has driven population divergence in phenotypic and
      behavioural traits and that selective release has affected both trait means and
      variances. Relaxed predation pressure is therefore likely to be one of the major
      ecological factors driving body size divergence on these islands. 

PMID- 24890836
TI  - Novel vaccination strategies against tuberculosis.
AB  - The tuberculosis (TB) pandemic continues to rampage despite widespread use of the
      BCG (Bacillus Calmette-Guerin) vaccine. Novel vaccination strategies are urgently
      needed to arrest global transmission and prevent the uncontrolled development of
      multidrug-resistant forms of Mycobacterium tuberculosis. Over the last two
      decades, considerable progress has been made in the field of vaccine development
      with numerous innovative preclinical candidates and more than a dozen vaccines in
      clinical trials. These vaccines are developed either as boosters of the current
      BCG vaccine or as novel prime vaccines to replace BCG. Given the enormous
      prevalence of latent TB infection, vaccines that are protective on top of an
      already established infection remain a high priority and a significant scientific
      challenge. Here we discuss the current state of TB vaccine research and
      development, our understanding of the underlying immunology, and the requirements
      for an efficient TB vaccine.

PMID- 24890840
TI  - Light-harvesting photocatalysis for water oxidation using mesoporous
      organosilica.
AB  - An organic-based photocatalysis system for water oxidation, with visible-light
      harvesting antennae, was constructed using periodic mesoporous organosilica
      (PMO). PMO containing acridone groups in the framework (Acd-PMO), a visible-light
      harvesting antenna, was supported with [Ru(II)(bpy)3(2+)] complex (bpy = 2,2'
      bipyridyl) coupled with iridium oxide (IrO(x)) particles in the mesochannels as
      photosensitizer and catalyst, respectively. Acd-PMO absorbed visible light and
      funneled the light energy into the Ru complex in the mesochannels through
      excitation energy transfer. The excited state of Ru complex is oxidatively
      quenched by a sacrificial oxidant (Na2S2O8) to form Ru(3+) species. The Ru(3+)
      species extracts an electron from IrO(x) to oxidize water for oxygen production.
      The reaction quantum yield was 0.34 %, which was improved to 0.68 or 1.2 % by the
      modifications of PMO. A unique sequence of reactions mimicking natural
      photosystem II, 1) light-harvesting, 2) charge separation, and 3) oxygen
      generation, were realized for the first time by using the light-harvesting PMO.

PMID- 24890842
TI  - [PET-CT for nuclear medicine diagnostics of multiple myeloma].
AB  - BACKGROUND: Functional or morphofunctional imaging modalities are used in myeloma
      patients for the diagnosis and therapy management within research protocols.
      Despite new staging criteria, which take into account the viability of a myeloma
      lesion, positron emission tomography (PET) is not used routinely. OBJECTIVES: The
      impact of PET is therefore open. The role of PET and PET computed tomography (PET
      CT) for the diagnosis and therapy management is discussed. RESULTS: The use of
      PET with 18F-fluorodeoxyglucose (FDG) allows the measurement of viable myeloma
      lesions and correlates with the stage of disease. A negative FDG examination
      correlates with a better prognosis. Furthermore, the number of focal lesions as
      well as the whole functional volume of myeloma lesions in FDG have a prognostic
      impact. Several studies have demonstrated the impact of FDG for the assessment of
      therapy monitoring and show that FDG is an earlier indicator for therapy response
      as compared to magnetic resonance imaging (MRI). The CT component of the new
      hybrid systems allows the assessment of osteolytic lesions in CT and their
      viability in FDG. The combination of PET with an MRT scanner allows the
      simultaneous measurement of bone marrow infiltration, focal lesions and their
      viability. CONCLUSION: The use of modern hybrid scanners, such as PET-CT and PET
      MRT facilitates the simultaneous measurement of viable myeloma lesions,
      osteolytic lesions and bone marrow infiltration in the whole body; therefore, it
      is expected that these imaging modalities will play a greater role both in
      diagnosis and therapy management.

PMID- 24890843
TI  - Tessellated gold nanostructures from Au144(SCH2CH2Ph)60 molecular precursors and
      their use in organic solar cell enhancement.
AB  - We report for the first time the fabrication of nanocomposite hole-blocking
      layers consisting of poly-3,4-ethylene-dioxythiophene:poly-styrene-sulfonate
      (PEDOT:PSS) thin films incorporating networks of gold nanoparticles assembled
      from Au144(SCH2CH2Ph)60, a molecular gold precursor. These thin films can be
      prepared reproducibly on indium tin oxide by spinning on it Au144(SCH2CH2Ph)60
      solutions in chlorobenzene, annealing the resulting thin film at 400  degrees C,
      and subsequently spinning PEDOT:PSS on top. The use of our nanocomposite hole
      blocking layers for enhancing the photoconversion efficiency of bulk
      heterojunction organic solar cells is demonstrated. By varying the concentration
      of Au144(SCH2CH2Ph)60 in the starting solution and the annealing time, different
      gold nanostructures were obtained ranging from individual gold nanoparticles
      (AuNPs) to tessellated networks of gold nanostructures (Tess-AuNPs). Improvement
      in organic solar cell efficiencies up to 10% relative to a reference cell is
      demonstrated with Tess-AuNPs embedded in PEDOT:PSS. 

PMID- 24890844
TI  - A new spectrofluorimetric method for determination of losartan potassium in
      rabbit plasma and its application to pharmacokinetic study.
AB  - A new spectrofluorimetric method to determine losartan potassium (LP) in rabbit
      plasma is described. The method was based on measuring the native fluorescence of
      LP in acidic medium. Optimum excitation and emission wavelengths were found to be
      248 nm and 410 nm, respectively, in methanol that was diluted with a sulfurous
      acid solution LP was extracted from rabbit plasma by methyl-tertiary-butyl-ether
      in acidic media and then back extracted with NaOH. The calibration curves were
      linear between 0.025 and 0.5 ug/mL with a lower limit of detection 0.004 ug/mL.
      Precision and accuracy values of the method were calculated as lower than 4.97%
      and +/- 5.68, respectively and the recovery of LP from rabbit plasma was higher
      than 91.1%. In addition, stability studies of LP in rabbit plasma were carried
      out and demonstrated its good stability at - 20  degrees C and at room
      temperature. The developed and validated method was successfully applied for
      estimating the pharmacokinetic parameters of LP following oral administrations of
      a single 10 mg LP/kg to rabbits and it could be concluded that the method can be
      applied to clinical trials.

PMID- 24890846
TI  - Efficacy of endothelin blockade in adults with Fontan physiology.
AB  - OBJECTIVE: Phosphodiesterase-5 inhibitors have shown to improve cardiac output
      and functional capacity in Fontan patients. We sought to test the efficacy and
      safety of endothelin blockade with bosentan in adult patients with Fontan
      physiology. DESIGN: Ten patients were enrolled and seven patients completed this
      single-center open-label clinical trial. Patients were treated with bosentan for
      4 months. Cardiac magnetic resonance imaging (MRI), 6-minute walking distance
      (6MWD), brain natriuretic peptide, and New York Heart Association functional
      class were compared before and after treatment using paired t-test. RESULTS: The
      6MWD improved by 73 m, from a mean of 435 m (standard deviation [SD] = 92,
      standard error [SE] = 35) to 508 m (SD = 93, SE = 35) (P = .03). MRI resting
      aortic flow increased from 3.3 L/minute (SD = 1.27, SE = 0.73) to 4.4 L/minute
      (SD = 0.9, SE = 0.54) (P = .03). New York Heart Association class was unchanged
      in three patients, improved in three patients and worsened in one patient. Brain
      natriuretic peptide, aspartate aminotransferase, and alanine aminotransferase did
      not change significantly. Of the three patients with elevated baseline bilirubin,
      two normalized at the completion of the study, while the other was unchanged.
      Mean duration of therapy was 4.1 +/- 0.51 months. Three adverse advents occurred.
      One patient complained of fatigue and chest pain after 87 days and withdrew from
      the study. After extensive workup, it was determined that her symptoms were not
      related to treatment. The second patient suffered palpitations and fatigue after
      75 days; no concerning arrhythmias were identified and symptoms improved with
      increased antiarrhythmic dose. The third patient developed fatigue on therapy and
      decided to stop therapy; fatigue improved following drug discontinuation. There
      were no deaths or hospitalizations. CONCLUSIONS: In this cohort of adult patients
      with Fontan physiology, endothelin blockade with bosentan resulted in improved
      6MWD and MRI-derived resting cardiac output, suggesting a positive effect on
      pulmonary vascular resistance and pulmonary blood flow. Bosentan was well
      tolerated and hepatic function was not adversely affected.

PMID- 24890847
TI  - Long-term outcomes among child and adolescent survivors of the 2010 Haitian
      earthquake.
AB  - BACKGROUND: We examined the prevalence and predictive factors of PTSD and
      depression in relation with peritraumatic distress, trauma exposure, and
      sociodemographic characteristics among children and adolescent who survived the
      2010 Haiti's earthquake. METHODS: We analyzed data collected between June and
      July 2012 from a sample of 872 participants aged 7 to 17 in 12 schools, door-to
      door canvassing and two centers for street children at Port-au-Prince.
      Participants completed the Impact of Event Scale Revised (IES-R), Peritraumatic
      Distress Inventory, Child Depression Inventory 2 (CDI), and sociodemographic and
      traumatic exposure questionnaires. RESULTS: Of 872 participants, respectively 322
      (36.93%); and 403 (46.21%) reported a clinically significant symptoms of PTSD and
      depression, which were significantly higher among girls. The best predictive
      variables are peritraumatic distress for PTSD (beta=0.53,P<.0001) a traumatic
      exposure for depression (beta=0.23,P<.0001). The comorbidity between PTSD and
      depression symptoms is 22.25%. CONCLUSIONS: This first study in children on the
      prevalence of PTSD and depression resulting from the 2010 Haiti earthquake
      demonstrates a need for improvement in treatment aimed at reducing PTSD and
      depression. Such treatment should be geared primarily toward girls, adolescents
      between the ages of 14 and 17 and those children and adolescents who have lost a
      family member in the earthquake.

PMID- 24890845
TI  - The need for speed in rodent locomotion analyses.
AB  - Locomotion analysis is now widely used across many animal species to understand
      the motor defects in disease, functional recovery following neural injury, and
      the effectiveness of various treatments. More recently, rodent locomotion
      analysis has become an increasingly popular method in a diverse range of
      research. Speed is an inseparable aspect of locomotion that is still not fully
      understood, and its effects are often not properly incorporated while analyzing
      data. In this hybrid manuscript, we accomplish three things: (1) review the
      interaction between speed and locomotion variables in rodent studies, (2)
      comprehensively analyze the relationship between speed and 162 locomotion
      variables in a group of 16 wild-type mice using the CatWalk gait analysis system,
      and (3) develop and test a statistical method in which locomotion variables are
      analyzed and reported in the context of speed. Notable results include the
      following: (1) over 90% of variables, reported by CatWalk, were dependent on
      speed with an average R(2) value of 0.624, (2) most variables were related to
      speed in a nonlinear manner, (3) current methods of controlling for speed are
      insufficient, and (4) the linear mixed model is an appropriate and effective
      statistical method for locomotion analyses that is inclusive of speed-dependent
      relationships. Given the pervasive dependency of locomotion variables on speed,
      we maintain that valid conclusions from locomotion analyses cannot be made unless
      they are analyzed and reported within the context of speed.

PMID- 24890848
TI  - Re: Differential influence of vemurafenib and dabrafenib on patients' lymphocytes
      despite similar clinical efficacy in melanoma.

PMID- 24890849
TI  - The clearance of oral high-risk human papillomavirus infection is impaired by
      long-term persistence of cervical human papillomavirus infection.
AB  - Persistence of high-risk (HR-) human papillomavirus (HPV) infection of the
      uterine cervix increases the risk of cervical cancer. Oral HPV infections are
      among potential covariates of long-term genotype-specific persistent cervical HR
      HPV infections. It is not known whether this persistence reflects inability of
      the host to reject HPV infections in general. A case-control setting was designed
      to estimate the covariates of long-term persistent cervical HR-HPV infections
      using multivariate generalized estimating equation (GEE) models. HPV was detected
      with PCR using GP05+/GP06+-primers and genotyped for 24 HPVs with a Multimetrix
      kit. The cases (n=43) included women who had genotype-specific persistent
      cervical HR-HPV infection for at least 24 months (24M+) and controls were women
      who tested repeatedly HPV-negative in their cervical samples (n=52). These women
      represent a sub-cohort of the Finnish Family HPV Study. The cases differed
      significantly from the HPV-negative controls in several aspects: they were
      younger, had a longer mean time to incident oral HPV infection (40.7 versus 23.6
      months), longer duration of oral HPV persistence (38.4 versus 14.1 months), and
      longer time to clearance of their oral HPV infection (50.0 versus 28.2 months).
      In multivariate GEE analysis, the second pregnancy during the follow up was the
      only independent predictor with significant protective effect against 24M+
      persistent cervical HR-HPV infections, OR of 0.15 (95% CI 0.07-0.34). To
      conclude, long-term persistent cervical HR-HPV infections are associated with a
      prolonged clearance of oral HR-HPV infections while new pregnancy protects
      against persistent cervical HR-HPV infections.

PMID- 24890850
TI  - Cardiac implantable electronic device removal in patients with left ventricular
      assist device associated infections.
AB  - INTRODUCTION: Heart failure patients with left ventricular assist devices (LVADs)
      are at risk for infection. Cardiac implantable electronic devices (CIEDs) are
      commonly present in these patients. The course of infections in patients with an
      LVAD and a CIED is not well described. METHODS AND RESULTS: We identified 6
      patients with a durable LVAD that underwent CIED removal because of an LVAD
      associated infection (LVADI). Patient and infection characteristics, management
      strategy, and clinical outcomes are described. All 6 patients were male, and the
      mean age was 59.6 years (range 43-72). Four of 6 patients had an ischemic
      cardiomyopathy, and 3 patients were diabetic. The median creatinine clearance for
      patients was 40.5 mg/dL (range 19-65). Five of 6 patients had a continuous flow
      LVAD placed as destination therapy. Four of 6 patients had a previous LVADI
      managed medically before the current infection leading to CIED removal. The
      indication for CIED removal was a bloodstream infection in 5 of 6 patients. Three
      of these patients had potential vegetations identified by echocardiography on
      device leads. The mean implanted age of the removed leads was 62 months (range 1
      179), and 1 of the 6 patients experienced a procedural complication (hematoma)
      from CIED removal. Four of 6 patients that underwent CIED removal for an LVADI
      had recurrence of infection. Five of 6 patients died during the initial
      presentation or from repeat presentation for infection. CONCLUSION: Despite CIED
      removal for an LVADI, recurrent infections are common and mortality remains high.

PMID- 24890851
TI  - Use of mid-upper arm circumference for determining overweight and overfatness in
      children and adolescents.
AB  - OBJECTIVE: To assess the use of mid-upper arm circumference (MUAC) for
      identification of overweight and overfatness in rural South African children and
      adolescents. METHODS: Anthropometric data (weight, height, MUAC and % body fat)
      from a cross-sectional sample of 978 black South African 5-14-year-olds were
      analysed. Receiver operating characteristic (ROC) curve analysis determined the
      validity of MUAC as a proxy for determining overweight and overfatness. FINDINGS:
      Area under the curve (AUC) results were generally high. Boys and girls aged 10-14
      years had ROC-AUC for overfatness classed as 'excellent', 0.97 and 0.98
      respectively. Cut-points in the MUAC distribution which optimised the ROC-AUC for
      identification of overfatness and obesity were determined for boys and girls aged
      5-9 and 10-14 years, and had high sensitivity and specificity. CONCLUSIONS: MUAC
      may have potential for clinical and surveillance applications as an accurate yet
      simple and widely available indicator of overweight and overfatness in children
      and adolescents in resource-poor settings.

PMID- 24890852
TI  - Couple-based Tibetan yoga program for lung cancer patients and their caregivers.

PMID- 24890853
TI  - Evaluation of a pilot promotora program for Latino forest workers in southern
      Oregon.
AB  - BACKGROUND: Forest work, an occupation with some of the highest injury and
      illness rates, is conducted primarily by Latino immigrant workers. This study
      evaluates a pilot program where promotoras (lay community health educators)
      provided occupational health and safety trainings for Latino forest workers.
      METHODS: Evaluation methods included a focus group, post-tests, and qualitative
      feedback. RESULTS: Community capacity to address working conditions increased
      through (i) increased leadership and community access to information and
      resources; and (ii) increased worker awareness of workplace health and safety
      rights and resources. Fear of retaliation remains a barrier to workers taking
      action; nevertheless, the promotoras supported several workers in addressing
      specific workplace issues. CONCLUSIONS: For working conditions to significantly
      improve, major structural influences need to be addressed. A long-term,
      organizationally supported promotora program can play a key role in linking and
      supporting change at the individual, interpersonal and community levels,
      contributing to and supporting structural change.

PMID- 24890854
TI  - Validation of a certified nurse-midwifery database for use in quality monitoring
      and outcomes research.
AB  - INTRODUCTION: Certified nurse-midwives (CNMs) and certified midwives (CMs) attend
      11% of US vaginal births, and CNM/CM databases include a rich source of
      information on the birth outcomes of women not generally available through
      obstetric electronic health records (oEHRs). Although CNM databases are in wide
      use, studies on their validity are sparse. We examined the validity of a practice
      specific CNM birth database compared with an oEHR in a large tertiary-care
      facility. METHODS: The study population consisted of all 3133 births in a large
      CNM practice that were entered into a practice-specific electronic birth database
      from 2001 to 2008. We assessed agreement with the oEHR overall and according to
      individual maternal demographic characteristics; obstetric, medical, and social
      risk factors; labor and birth information; and newborn characteristics. We also
      evaluated whether there were differences in agreement according to early versus
      later study periods and by years of CNM clinical experience. RESULTS: Overall
      agreement between the CNM birth database and the oEHR was 92.4%. Agreement
      between the CNM birth database and the oEHR was greater than 90% for maternal
      age, race/ethnicity, route and type of birth, major genital tract trauma, newborn
      weight, and primary clinician attending the birth. Lower agreement rates for
      smoking, total weight gain in pregnancy, beginning of pregnancy body mass index,
      and anesthesia for birth were due, in part, to missing information in the oEHR.
      Agreement did not vary significantly by early versus late study periods or by
      years of CNM clinical experience. DISCUSSION: Findings indicate that a CNM/CM
      birth database is a valid data source for quality monitoring and outcomes
      research and may contain more complete information for some variables than the
      oEHR.

PMID- 24890855
TI  - Care professionals' understanding of the new criminal offences created by the
      Mental Capacity Act 2005.
AB  - OBJECTIVES: Implemented in 2007, the Mental Capacity Act (MCA) 2005 codified
      decision-making for adults unable to make decisions for themselves in England and
      Wales. Among other changes, two new offences of wilful neglect and ill-treatment
      were created under Section 44. Our study explored how the MCA was being
      implemented in community-based dementia care, focusing on frontline practice.
      METHOD: Using qualitative longitudinal methodology, we interviewed 279
      practitioners, in the London and South-East area of England, two or three times
      over 3 years. We applied framework analysis to identify and delineate recurrent
      themes. RESULTS: Views of the new offences were positive overall, but
      understanding ranged from partial to non-existent among some participants.
      CONCLUSIONS: Clinicians may be increasingly called upon to provide advice on
      whether an alleged victim or perpetrator lacks decision-making capacity in cases
      of suspected elder abuse. They need to be aware of the new criminal offences to
      ensure that people with dementia, among others, are not abused and that abusers
      are brought to account.

PMID- 24890856
TI  - aglgenes, A curated and searchable database of archaeal N-glycosylation pathway
      components.
AB  - Whereas N-glycosylation is a posttranslational modification performed across
      evolution, the archaeal version of this protein-processing event presents a
      degree of diversity not seen in either bacteria or eukarya. Accordingly, archaeal
      N-glycosylation relies on a large number of enzymes that are often species
      specific or restricted to a select group of species. As such, there is a need for
      an organized platform upon which amassing information about archaeal
      glycosylation (agl) genes can rest. Accordingly, the aglgenes database provides
      detailed descriptions of experimentally characterized archaeal N-glycosyation
      pathway components. For each agl gene, genomic information, supporting literature
      and relevant external links are provided at a functional intuitive web-interface
      designed for data browsing. Routine updates ensure that novel experimental
      information on genes and proteins contributing to archaeal N-glycosylation is
      incorporated into aglgenes in a timely manner. As such, aglgenes represents a
      specialized resource for sharing validated experimental information online,
      providing support for workers in the field of archaeal protein glycosylation.
      Database URL: www.bgu.ac.il/aglgenes. 

PMID- 24890857
TI  - Inverse modulation of the energy sensor Snf1-related protein kinase 1 on hypoxia
      adaptation and salt stress tolerance in Arabidopsis thaliana.
AB  - Terrestrial plants are exposed to complex stresses of high salt-induced abscisic
      acid (ABA) and submergence-induced hypoxia when seawater floods fields. Many
      studies have investigated plant responses to individual stress conditions, but
      not so much for coupled or sequentially imposed stresses. We examined molecular
      regulatory mechanisms of gene expression underlying the cellular responses
      involved in crosstalk between salt and hypoxia stresses. Salt/ABA- and AtMYC2
      dependent induction of a synthetic ABA-responsive element and the native RD22
      promoters were utilized in our cell-based functional assays. Such promoter-based
      reporter induction was largely inhibited by hypoxia and hypoxia-inducible AKIN10
      activity. Biochemical analyses showed that AKIN10 negatively modulates AtMYC2
      protein accumulation via proteasome activity upon AKIN10 kinase activity
      dependent protein modification. Further genetic analysis using transgenic plants
      expressing AKIN10 provided evidence that AKIN10 activity undermined AtMYC2
      dependent salt tolerance. Our findings unravel a novel molecular interaction
      between the key signalling constituents leading crosstalk between salt and
      hypoxia stresses in Arabidopsis thaliana under the detrimental condition of
      submergence in saltwater. 

PMID- 24890859
TI  - Prioritization of patient-related factors according to renal function in
      antidiabetic drug selection: the REDIM Project.
AB  - AIMS: Few studies have evaluated how physicians prioritize renal function among
      other patient-related factors when stepping-up in antidiabetic treatment.
      METHODS: The REDIM Spanish national online survey included 550 internists. We
      firstly tested proficiency in chronic kidney disease (Agrawal's Questionnaire)
      and motivation in diabetes (DAS-3p Questionnaire). We then analyzed how
      physicians prioritized renal function, age, weight, glycemic control, non-renal
      co-morbidities and patient perceptions in five varying fictitious clinical
      scenarios (generic; ambulatory vs. high cardiovascular risk hospitalized patient,
      for estimated glomerular filtration rates (eGFRs)=50 vs. 25 ml/min/1.73 m(2)). We
      assigned every item a score (from 5 to 0, highest to lowest relevance) per
      physician and compared mean values between clinical scenarios using the t-test
      for independent means (nominal significance at p<0.05). RESULTS: Completion rate
      was 57.5% (N=316; mean age, 46.3 years; men, 71%). Average scores were 22.6 +/-
      3.9 (possible range [0-30]) for Agrawal's Questionnaire and 4.1 +/- 0.6 (range [1
      5]) for DAS-3p Questionnaire. In the generic scenario, renal function had the
      highest priority (mean=3.36 +/- 1.66, range [0-5]). When eGFR was set at 50
      ml/min/1.73 m(2), physicians prioritized glycemic control for ambulatory
      (mean=3.23 +/- 1.59) and non-renal co-morbidities for hospitalized patients
      (mean=3.20 +/- 1.68) over renal function (mean=3.18 +/- 1.77 for ambulatory,
      p=0.032; mean=3.11 +/- 1.65 for hospitalized patients, p=0.002). When eGFR was
      subsequently lowered to 25 ml/min/1.73 m(2), renal function again led priorities
      (mean values=3.73 +/- 2.05 for ambulatory and 3.75 +/- 1.96 for hospitalized
      patients; both p<0.001). CONCLUSIONS: Knowledge of the degree of renal function
      impairment induced physicians to prioritize patient-related factors differently
      when adding a second antidiabetic drug. Renal function led priorities when
      severely impaired.

PMID- 24890860
TI  - Adequacy of hyaluronan binding assay and a new fertility index derived from it
      for measuring of male fertility potential and the efficacy of supplement therapy.
AB  - The aim of the study was to statistically prove that the HBA((r)) test is an
      efficient practical method for andrologists to determine the fertility potential
      as well as to measure the efficiency of oral supplement therapy in case of male
      infertility. In the study, 175 patients were involved and it also included the
      follow-up studies of 39 patients after supplement therapy. Completing the
      'classic' spermatological parameters with the results of HBA((r)) test, the
      authors have also determined a new fertility index to be used for practical
      rating of the measure of fertility potential. After the supplement therapy, both
      sperm density and hyaluronan binding capacity increased significantly. The
      authors are convinced that the HBA((r)) analysis is an objective, standardisable
      test, which provides a better approach to fertility potential. This analysis
      enables us to detect spermatozoa that were previously misjudged as normal by
      morphological assay and also makes the efficiency of the therapy more measurable.

PMID- 24890858
TI  - Phase II trial of bortezomib plus doxorubicin in hepatocellular carcinoma
      (E6202): a trial of the Eastern Cooperative Oncology Group.
AB  - PURPOSE: To evaluate the efficacy and tolerability of bortezomib in combination
      with doxorubicin in patients with advanced hepatocellular carcinoma, and to
      correlate pharmacodynamic markers of proteasome inhibition with response and
      survival. EXPERIMENTAL DESIGN: This phase II, open-label, multicenter study
      examined the efficacy of bortezomib (1.3 mg/m(2) IV on d1, 4, 8, 11) and
      doxorubicin (15 mg/m(2) IV on d1, 8) in 21-day cycles. The primary endpoint was
      objective response rate. RESULTS: Best responses in 38 treated patients were 1
      partial response (2.6 %), 10 (26.3 %) stable disease, and 17 (44.7 %) progressive
      disease; 10 patients were unevaluable. Median PFS was 2.2 months. Median OS was
      6.1 months. The most common grade 3 to 4 toxicities were hypertension, glucose
      intolerance, ascites, ALT elevation, hyperglycemia and thrombosis/embolism. Worse
      PFS was seen in patients with elevated IL-6, IL-8, MIP-1alpha and EMSA for NF
      kappaB at the start of treatment. Worse OS was seen in patients with elevated IL
      8 and VEGF at the start of treatment. Patients had improved OS if a change in the
      natural log of serum MIP-1alpha/CCL3 was seen after treatment. RANTES/CCL5 levels
      decreased significantly with treatment. CONCLUSIONS: The combination of
      doxorubicin and bortezomib was well-tolerated in patients with hepatocellular
      carcinoma, but the primary endpoint was not met. Exploratory analyses of markers
      of proteasome inhibition suggest a possible prognostic and predictive role and
      should be explored further in tumor types for which bortezomib is efficacious.

PMID- 24890861
TI  - Fate of the buccal bone at implants placed early, delayed, or late after tooth
      extraction analyzed by cone beam CT: 10-year results from a randomized,
      controlled, clinical study.
AB  - AIM: To present 10-year cone beam CT (CBCT) data on the fate of buccal bone at
      single-tooth implants placed early, delayed, or late after tooth extraction.
      MATERIAL AND METHODS: Sixty-three of 72 patients, originally randomly allocated
      to three equal-size groups, received a single-tooth implant on average 10 days
      (Ea; N = 22), 3 months (De; N = 22), or 1.5 years (La; N = 19) after tooth
      extraction. Healing abutments were mounted after a 3-month period of submerged
      healing and metalceramic crowns were cemented after one additional month. At the
      second stage surgery, presence of buccal bone defects (dehiscences or intrabony)
      and their dimensions were registered. CBCT scans recorded with a Scanora((r)) 3D
      unit and standardized periapical (PA) radiographs of the implants were obtained
      at the 10-year control. Interproximal bone levels (i.e., the distance from the
      implant platform to the first bone-to-implant contact; BIC) measured in CBCT
      image sections and PA were compared, and the buccal bone level was determined in
      the CBCT images. RESULTS: Two Ea and one De implants failed to osseointegrate.
      Forty-nine patients attended the 10-year control and due to poor quality of 5
      CBCT scans, useful CBCT images were available from 44 patients (Ea:12, De:17,
      La:15). No significant differences between CBCT and PA images in measurements of
      the interproximal bone levels were observed. Ten years after implant placement,
      BIC at the buccal aspect was located on average 2 mm apically to the implant
      platform (2.39 +/- 1.06 mm [median = 2.36] for Ea, 2.22 +/- 0.99 mm [median =
      2.16] for De, and 1.85 +/- 0.65 mm [median = 1.95] for La implants) with no
      significant difference among the groups (P = 0.20). Mean buccal bone level (bBL)
      for implants with an intrabony or a dehiscence defect at second stage surgery was
      2.51 +/- 1.12 mm [median = 2.70] and 2.84 +/- 0.70 mm [median = 2.79],
      respectively, while 1.78 +/- 0.74 mm [median = 1.93] for the implants with no
      defect. The difference in bBL between the implants without a defect and those
      with a dehiscence was significant at 10 years (P = 0.0005). CONCLUSION: Time of
      placement of single-tooth implants after tooth extraction did not significantly
      influence the peri-implant buccal bone level, while presence of a buccal bone
      dehiscence at second stage surgery resulted in significantly more apically
      located BIC buccally at 10 years.

PMID- 24890862
TI  - Specific photosynthetic rate enhancement by cyanobacteria coated onto paper
      enables engineering of highly reactive cellular biocomposite "leaves".
AB  - We describe a latex wet coalescence extrusive coating method that produces up to
      10-fold specific photosynthetic rate enhancements by nitrate-limited non-growing
      cyanobacteria deposited onto paper, hydrated and placed in the gas-phase of small
      tube photobioreactors. These plant leaf-like biocomposites were used to study the
      tolerance of cyanobacteria strains to illumination and temperature using a solar
      simulator. We report sustained CO2 absorption and O2 production for 500 h by
      hydrated gas-phase paper coatings of non-growing Synechococcus PCC7002,
      Synechocystis PCC6803, Synechocystis PCC6308, and Anabaena PCC7120. Nitrate
      starved cyanobacteria immobilized on the paper surface by the latex binder did
      not grow out of the coatings into the bulk liquid. The average CO2 consumption
      rate in Synechococcus coatings is 5.67 mmol m(-2)  h(-1) which is remarkably
      close to the rate reported in the literature for Arabidopsis thaliana leaves
      under similar experimental conditions (18 mmol m(-2)  h(-1) ). We observed
      average ratios of oxygen production to carbon dioxide consumption (photosynthetic
      quotient, PQ) between 1.3 and 1.4, which may indicate a strong dependence on
      nitrate assimilation during growth and was used to develop a non-growth media
      formulation for intrinsic kinetics studies. Photosynthetic intensification
      factors (PIF) (O2 production by nitrate-limited cyanobacteria in latex
      coatings/O2 produced by nitrate-limited cell suspensions) in cyanobacteria
      biocomposites prepared from wet cell pellets concentrated 100- to 300-fold show 7
      10 times higher specific reactivity compared to cells in suspension under
      identical nitrate-limited non-growth conditions. This is the first report of
      changes of cyanobacteria tolerance to temperature and light intensities after
      deposition as a thin coating on a porous matrix, which has important implications
      for gas-phase photobioreactor design using porous composite materials. Cryo
      fracture SEM and confocal microscopy images of cell coating distribution on the
      paper biocomposite suggest that the spatial arrangement of the cells in the
      coating can affect photoreactivity. This technique could be used to fabricate
      very stable, multi-organism composite coatings on flexible microfluidic devices
      in the gas-phase capable of harvesting light in a broader range of wavelengths,
      to optimize thermotolerant, desiccation tolerant, or halotolerant cyanobacteria
      that produce O2 with secretion of liquid-fuel precursors synthesized from CO2 .

PMID- 24890863
TI  - Aqueous complexes for efficient size-based separation of americium from curium.
AB  - Complexation of the adjacent actinide ions americium(III) and curium(III) by the
      ligand N,N'-bis[(6-carboxy-2-pyridyl)methyl]-1,10-diaza-18-crown-6 (H2bp18c6) in
      aqueous solution was studied to quantify and characterize its americium/curium
      selectivity. Liquid-liquid extraction and spectrophotometric titration indicated
      the presence of both fully deprotonated and monoprotonated complexes,
      An(bp18c6)(+) and An(Hbp18c6)(2+) (An = Am or Cm), at the acidities that would be
      encountered when treating nuclear wastes. The stability constants of the
      complexes in 1 M NaNO3 determined using competitive complexation were log beta101
      = 15.49 +/- 0.06 for Am and 14.88 +/- 0.03 for Cm, indicating a reversal of the
      usual order of complex stability, where ligands bind the smaller Cm(III) ion more
      tightly than Am(III). The Am/Cm selectivity of bp18c6(2-) that is defined by the
      ratio of the Am and Cm stability constants (beta101 Am/beta101 Cm = 4.1) is the
      largest reported so far for binary An(III)-ligand complexes. Theoretical density
      functional theory calculations using the B3LYP functional suggest that the
      ligand's size-selectivity for larger 4f- and 5f-element cations arises from
      steric constraints in the crown ether ring. Enhanced 5f character in molecular
      orbitals involving actinide-nitrogen interactions is predicted to favor
      actinide(III) complexation by bp18c6(2-) over the complexation of similarly sized
      lanthanide(III) cations. 

PMID- 24890865
TI  - Echocardiographic evaluation of univentricular physiology and cavopulmonary
      shunts.
AB  - The term univentricular heart (UH) defines complex congenital heart disease that
      lacks a pulmonic ventricular chamber either in the original anatomy or the final
      palliation. The prevalence of patients with this type of physiology continues to
      increase due to improved surgical palliative procedures. This review will outline
      the physiology, complications, and echocardiographic approach to image patients
      with palliated UH. 

PMID- 24890864
TI  - On the necessity of dissecting sequence similarity scores into segment-specific
      contributions for inferring protein homology, function prediction and annotation.
AB  - BACKGROUND: Protein sequence similarities to any types of non-globular segments
      (coiled coils, low complexity regions, transmembrane regions, long loops, etc.
      where either positional sequence conservation is the result of a very simple,
      physically induced pattern or rather integral sequence properties are critical)
      are pertinent sources for mistaken homologies. Regretfully, these considerations
      regularly escape attention in large-scale annotation studies since, often, there
      is no substitute to manual handling of these cases. Quantitative criteria are
      required to suppress events of function annotation transfer as a result of false
      homology assignments. RESULTS: The sequence homology concept is based on the
      similarity comparison between the structural elements, the basic building blocks
      for conferring the overall fold of a protein. We propose to dissect the total
      similarity score into fold-critical and other, remaining contributions and
      suggest that, for a valid homology statement, the fold-relevant score
      contribution should at least be significant on its own. As part of the article,
      we provide the DissectHMMER software program for dissecting HMMER2/3 scores into
      segment-specific contributions. We show that DissectHMMER reproduces HMMER2/3
      scores with sufficient accuracy and that it is useful in automated decisions
      about homology for instructive sequence examples. To generalize the dissection
      concept for cases without 3D structural information, we find that a dissection
      based on alignment quality is an appropriate surrogate. The approach was applied
      to a large-scale study of SMART and PFAM domains in the space of seed sequences
      and in the space of UniProt/SwissProt. CONCLUSIONS: Sequence similarity core
      dissection with regard to fold-critical and other contributions systematically
      suppresses false hits and, additionally, recovers previously obscured homology
      relationships such as the one between aquaporins and formate/nitrite transporters
      that, so far, was only supported by structure comparison.

PMID- 24890866
TI  - Enantioselective degradation of (2RS,3RS)-paclobutrazol in peach and mandarin
      under field conditions.
AB  - In this study we investigated the enantioselective degradation of (2RS,3RS)
      paclobutrazol in peach and mandarin fruits under field conditions after foliar
      treatment at 500 mg active ingredient/L using a Lux Cellulose-1 chiral column on
      a reverse-phase liquid chromatography-tandem mass spectrometry system.
      Degradations of paclobutrazol in both fruits followed first-order kinetics, with
      half-lives of about 9 days. Initial deposits were 1.63 mg/kg on peach and 1.99
      mg/kg on mandarin; terminal concentrations were lower than 0.05 mg/kg, which was
      acceptable in most cases. As anticipated, paclobutrazol levels in peels of mature
      mandarin were about 6.3 times higher than in pulp, indicating the potential risk
      of peel consumption. We also observed that paclobutrazol degradation in mature
      mandarin was relatively slow, indicating it might not be efficient enough to hold
      mandarin fruits on trees for lowering paclobutrazol concentrations. Significant
      enantioselectivity was observed: the (2R,3R)-enantiomer was preferentially
      degraded in mandarin (whole fruit, peels, and pulp) but enriched in peach.
      Because of its more rapid degradation in mandarin and the lower levels observed
      in pulp compared with peels, potential endocrine-related side effects due to the
      (2R,3R)-enantiomer pose less of a risk in mandarin than in peach.

PMID- 24890867
TI  - In response to "patient-centered blood management".

PMID- 24890868
TI  - Different binding sites of bovine organic anion-transporting polypeptide1a2 are
      involved in the transport of different fluoroquinolones.
AB  - Because of their wide distribution and capability of transporting a large variety
      of compounds, organic anion-transporting polypeptides (OATPs) have been
      extensively recognized as crucial players in absorption, distribution, and
      excretion of various drugs. OATP1A2 was the first cloned human OATP and has been
      found to transport wide range of endogenous and exogenous compounds. Bovine
      Oatp1a2 (bOatp1a2) shares high homology with human OATP1A2 and is considered the
      functional ortholog of the latter. Previous study in our laboratory demonstrated
      that bOatp1a2 transport of estrone-3-sulfate (ES) exhibited biphasic saturation
      kinetics. In the present study, we investigated the transport function of
      bOatp1a2 for four different quinolone antibacterial agents (enrofloxacin,
      levofloxacin, norfloxacin, and ciprofloxacin) and found that all the tested
      fluoroquinolones can be transported by bOatp1a2. Further studies showed that
      different binding sites are responsible for the transport of different
      fluoroquinolones. Both ciprofloxacin and norfloxacin exhibited biphasic
      saturation kinetics. The Kms of the high- and low-affinity components for
      ciprofloxacin were 3.80 +/- 0.85 MUM and 182 +/- 31 MUM, respectively, while
      those for norfloxacin were 24.7 +/- 0.1 MUM and 393 +/- 79 MUM, respectively.
      Enrofloxacin and levofloxacin showed an inhibitory effect on the uptake of only
      the high concentration of ES and thus may be transported by the low-affinity site
      for ES. Interestingly, enrofloxacin and levofloxacin demonstrated an activation
      effect on ES uptake at the high-affinity binding site. These results suggested
      that multiple binding sites within the structure of bOatp1a2 may be responsible
      for the uptake of different quinolone antimicrobial agents. 

PMID- 24890869
TI  - Premature ovarian failure is a major risk factor for cancer-related sexual
      dysfunction.

PMID- 24890870
TI  - Granulomatous slack skin with systemic involvement and a fatal outcome in an
      adolescent.

PMID- 24890872
TI  - Carbohydrate-functionalized locked nucleic acids: oligonucleotides with
      extraordinary binding affinity, target specificity, and enzymatic stability.
AB  - Three different C5-carbohydrate-functionalized LNA uridine phosphoramidites were
      synthesized and incorporated into oligodeoxyribonucleotides. C5-Carbohydrate
      functionalized LNA display higher affinity toward complementary DNA/RNA targets
      (DeltaTm/modification up to +11.0  degrees C), more efficient discrimination of
      mismatched targets, and superior resistance against 3'-exonucleases compared to
      conventional LNA. These properties render C5-carbohydrate-functionalized LNAs as
      promising modifications in antisense technology and other nucleic acid targeting
      applications. 

PMID- 24890873
TI  - R705H mutation of MYH9 is associated with MYH9-related disease and not only with
      non-syndromic deafness DFNA17.
AB  - MYH9-related disease (MYH9-RD) is a rare autosomal dominant disease caused by
      mutation of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA
      (NMMHC-IIA). MYH9-RD patients have macrothrombocytopenia and granulocyte
      inclusions (pathognomonic sign of the disease) containing wild-type and mutant
      NMMHC-IIA. During life they might develop sensorineural hearing loss, cataract,
      glomerulonephritis, and elevation of liver enzymes. One of the MYH9 mutations,
      p.R705H, was previously reported to be associated with DFNA17, an autosomal
      dominant non-syndromic sensorineural hearing loss without any other features
      associated. We identified the same mutation in two unrelated families, whose four
      affected individuals had not only hearing impairment but also thrombocytopenia,
      giant platelets, leukocyte inclusions, as well as mild to moderate elevation of
      some liver enzymes. Our data suggest that DFNA17 should not be a separate genetic
      entity but part of the wide phenotypic spectrum of MYH9-RD characterized by
      congenital hematological manifestations and variable penetrance and expressivity
      of the extra-hematological features. 

PMID- 24890875
TI  - Vaccine responsiveness in the elderly: best practice for the clinic.
AB  - The success of vaccines developed since the beginning of the 20th century, has
      enabled the conquest of several childhood diseases preventing death and or
      disability for millions of children. But, globally, the number of children will
      soon be surpassed by the number of adults over the age of 65. The active
      lifestyle of these older individuals, coupled with a degree of immune deficiency
      recognised within this population will lead to a change in the profile of
      diseases affecting the elderly. The challenge for policy makers and also those
      involved in primary healthcare is how to protect this population from
      communicable diseases and keep them healthy, autonomous and independent when
      vaccines in the main have been developed for use on children and young adults. 

PMID- 24890874
TI  - Signal propagation in multi-layer DNAzyme cascades using structured chimeric
      substrates.
AB  - Signal propagation through enzyme cascades is a critical component of information
      processing in cellular systems. Although such systems have potential as
      biomolecular computing tools, rational design of synthetic protein networks
      remains infeasible. DNA strands with catalytic activity (DNAzymes) are an
      attractive alternative, enabling rational cascade design through predictable base
      pair hybridization principles. Multi-layered DNAzyme signaling and logic cascades
      are now reported. Signaling between DNAzymes was achieved using a structured
      chimeric substrate (SCS) that releases a downstream activator after cleavage by
      an upstream DNAzyme. The SCS can be activated by various upstream DNAzymes, can
      be coupled to DNA strand-displacement devices, and is highly resistant to
      interference from background DNA. This work enables the rational design of
      synthetic DNAzyme regulatory networks, with potential applications in
      biomolecular computing, biodetection, and autonomous theranostics. 

PMID- 24890876
TI  - Primary cutaneous CD4/CD8-/- TCRalphabeta T-cell lymphoma.

PMID- 24890878
TI  - L-lysine dose dependently delays gastric emptying and increases intestinal fluid
      volume in humans and rats.
AB  - BACKGROUND: Novel sensory inputs for the control of food intake and
      gastrointestinal (GI) function are of increasing interest due to the rapid
      increase in nutrition-related diseases. The essential amino acid L-lysine was
      demonstrated to have a selective impact on food intake, gastric emptying, and
      intestinal transit in rats, thus indicating a potential novel direct sensory
      input to assess dietary protein content and quality. The aim of this study was to
      assess translational aspects of this finding and to investigate the dose
      dependent effect of L-lysine on human and rat GI function. METHODS: L-lysine
      doses from 0-800 mg in rats and 0.5-7.5 g in humans were analyzed for their
      effect on gastric emptying and GI secretion. Human GI function was assessed non
      invasively using magnetic resonance imaging (MRI), rat data were acquired using
      standard lethal measurement methods. L-lysine dose dependently delayed gastric
      emptying and stimulated GI secretion in rats as reflected by residual phenol red
      content and increased gastric wet weight. KEY RESULTS: The dose-dependent delay
      in gastric emptying observed in rats was confirmed in humans with an increase in
      halftime of gastric emptying of 4 min/g L-lysine, p < 0.01. Moreover, a dose
      dependent increase in intestinal fluid accumulation was observed (0.4 mL/min/g L
      lysine, p < 0.0001). No effect on alkaline tide, glucose concentration,
      hematocrit, or visceral sensations was detected. CONCLUSIONS & INFERENCES: This
      translational study demonstrates comparable dose-dependent effects of
      intragastric L-lysine on GI function in humans and rats and suggests a broader
      role for individual amino acids in the control of GI motility and secretion in
      vivo.

PMID- 24890879
TI  - A cross-sectional survey of antimicrobial stewardship strategies in UK hospitals.
AB  - WHAT IS KNOWN AND OBJECTIVE: Antimicrobial stewardship programmes describe
      strategies to optimize antimicrobial prescribing and utilization, minimize
      resistance and improve patient outcomes. Strategies in hospitals are usually
      implemented by multidisciplinary antimicrobial teams (AMTs). The objective of
      this study was to describe the profile and activities of AMTs within hospitals in
      the United Kingdom (UK). METHOD: All hospitals within the UK (n = 836) were
      included, and a prepiloted questionnaire was mailed to the 'Director of
      Pharmacy'. Non-respondents were mailed up to two reminder questionnaires at two
      weekly intervals. Main outcome measures are as follows: existence and remit of
      the AMTs; availability of antimicrobial-prescribing policies, aims, scope and
      methods of dissemination; and monitoring and feedback provided on antimicrobial
      policy adherence. RESULTS: Response rate was 33% (n = 273). Completed
      questionnaires analysed were n = 226. Eighty-two (n = 186) of respondents
      indicated the presence of an AMT within the hospital, with 95% of these (n = 177)
      reporting an antimicrobial pharmacist as part of the team. All AMTs (n = 186)
      were involved in development of an antimicrobial policy and almost all (99% n =
      184) promoted adherence and restricting use of specific antimicrobials (97% n =
      180). Ninety-eight per cent of respondents (n = 222) reported the availability of
      a local antimicrobial-prescribing policy within the hospital with this
      disseminated mainly through the hospital intranet (98% n = 217). Adherence to
      policy was measured mainly through audits measuring the appropriateness of
      antimicrobial use against the local policy (76% n = 169). Hospitals in England (P
      = 0.010), tertiary care hospitals (P = 0.021) and bed capacity >500 (P < 0.001)
      were more likely to have an AMT, as were hospitals with an accident and emergency
      department (P < 0.001), an infectious diseases unit (P = 0.019) and a
      microbiology department (P < 0.001). Audits to measure policy adherence were more
      likely (P < 0.001) if an AMT was present. The only variable retained in bivariate
      logistic regression was the presence of a microbiology unit, with an odds ratio
      of 14.1 (95% CI 6.02-33.33, P < 0.001). WHAT IS NEW AND CONCLUSIONS: Although
      most respondents reported an antimicrobial-prescribing policy, less had an AMT.
      Despite recent government and regional initiatives, further improvements in
      antimicrobial stewardship are still required.

PMID- 24890877
TI  - Circadian endocrine rhythms: the hypothalamic-pituitary-adrenal axis and its
      actions.
AB  - The stress system effectively restores the internal balance--or homeostasis--of
      living organisms in the face of random external or internal changes, the
      stressors. This highly complex system helps organisms to provide a series of
      neuroendocrine responses to stressors--the stress response--through coordinated
      activation of the hypothalamic-pituitary-adrenal (HPA) axis and the locus
      coeruleus/norepinephrine autonomic nervous systems. In addition to stressors,
      life is influenced by daily light/dark changes due to the 24-h rotation of Earth.
      To adjust to these recurrent day/night cycles, the biological clock system
      employs the heterodimer of transcription factors circadian locomotor output cycle
      kaput/brain-muscle-arnt-like protein 1 (CLOCK/BMAL1), along with a set of other
      transcription factors, to regulate the circadian pattern of gene expression.
      Interestingly, the stress system, through the HPA axis, communicates with the
      clock system; therefore, any uncoupling or dysregulation could potentially cause
      several disorders, such as metabolic, autoimmune, and mood disorders. In this
      review, we discuss the biological function of the two systems, their
      interactions, and the clinical implications of their dysregulation or uncoupling.

PMID- 24890880
TI  - A system for automated noise parameter measurements on MR preamplifiers and
      application to high B(0) fields.
AB  - A noise figure and noise parameter measurement system was developed that consists
      of a combination spectrum and network analyzer, preamplifier, programmable power
      supply, noise source, tuning board, and desktop computer. The system uses the Y
      factor method for noise figure calculation and allows calibrations to correct for
      a decrease in excess noise ratio between the noise source and device under test,
      second stage (system) noise, ambient temperature variations, and available gain
      of the device under test. Noise parameters are extracted by performing noise
      figure measurements at several source impedance values obtained by adjusting an
      electronically controlled tuner. Results for several amplifiers at 128 MHz and
      200 MHz agree with independent measurements and with the corresponding
      datasheets. With some modifications, the system was also used to characterize the
      noise figure of MRI preamplifiers in strong static magnetic fields up to 9.4 T.
      In most amplifiers tested the gain was found to be reduced by the magnetic field,
      while the noise figure increased. These changes are detrimental to signal quality
      (SNR) and are dependent on the electron mobility and design of the amplifier's
      semiconductor devices. Consequently, gallium arsenide (GaAs) field-effect
      transistors are most sensitive to magnetic fields due to their high electron
      mobility and long, narrow channel, while silicon-germanium (SiGe) bipolar
      transistor amplifiers are largely immune due to their very thin base.

PMID- 24890881
TI  - What are the relations of thinking about groups and theory of mind?

PMID- 24890882
TI  - Adjuvant anticholinesterase therapy for the management of epilepsy-induced memory
      deficit: a critical pre-clinical study.
AB  - Epilepsy is one of the major neurological disorders still awaiting safer drugs
      with improved antiepileptic effect and lesser side effects. Apart from epilepsy
      itself, AEDs also have been shown to induce cognitive impairment in patients with
      epilepsy. There are limited data for the treatment of this menace. As cholinergic
      approach has widely been practiced for the restoration of memory in various
      neurodegenerative disorders, this study was envisaged to evaluate add on effect
      of acetylcholinesterase inhibitor (tacrine) with phenytoin in pentylenetetrazole
      kindling-induced learning and memory deficit in mice. In this study, mice were
      kindled using subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.; at
      interval of 48 +/- 2 hr) and successfully kindled animals were divided into
      different groups and treated with vehicle, phenytoin and phenytoinin in
      combination with tacrine (0.3 mg/kg), atropine (1 mg/kg) and tacrine + atropine.
      Effect of different interventions on learning and memory was evaluated using
      elevated plus maze and passive shock avoidance on days 5, 10, 15 and 20.
      Phenytoin-treated kindled animals were associated with learning and memory
      deficit, while tacrine supplementation improved memory deficit with increased
      seizure severity score. Atropine treatment significantly reversed the protective
      effect of tacrine. Neurochemical findings also support the behavioural finding of
      the study. Our results suggest the use of anticholinesterases, with better
      seizure tolerance, for the management of cognitive impairment of epilepsy, as
      adjunct therapy. 

PMID- 24890884
TI  - Kidney cancer: bisphosphonates in the era of antiangiogenic targeted therapy.
AB  - Bone is the second most common metastatic site in patients presenting with
      metastatic renal cell carcinoma. Bisphosphonates have been approved to reduce
      bone pain and the risk of skeletal-related events (SREs) in such patients;
      however, new research suggests bisphosphonates do not improve survival or prevent
      development of SREs.

PMID- 24890883
TI  - Pushing the boundaries of ureteroscopy: current status and future perspectives.
AB  - Substantial advances in ureteroscopy have resulted in the incorporation of this
      procedure into routine urological practice in many centres worldwide.
      Subsequently, an abundance of clinical data and technological progression have
      enabled the development of novel solutions that have increased the efficacy of
      ureteroscopy, and reduced associated morbidity and costs. In addition the
      indications for this retrograde approach have been expanded, and pyelocalyceal
      diverticulum, infundibular stenosis, urolithiasis in pregnant women or in
      patients with urinary diversions, as well as upper urinary tract tumours can now
      be managed using this methodology. New endoscopes are continuously developed,
      with different manufacturers choosing various technical solutions to further
      increase the efficacy and safety-and sometimes decrease costs-of ureteroscopy,
      including miniaturization, inclusion of digital optical systems and dual working
      channels, and the introduction of disposable apparatus. The holmium laser,
      currently the most-versatile energy source available, enables tissue incision,
      tumour ablation, and intracorporeal lithotripsy. Modern ancillary instruments are
      diverse, flexible, and durable, and novel devices used in daily clinical practice
      can minimize ascendant migration of stone fragments and, therefore, decrease the
      failure rate of the retrograde ureteroscopic approach. However, the peak of
      ureteroscopy evolution seems to remain distant, with further improvement of
      endoscopes and ancillary instruments, and robot-assisted ureteroscopy
      representing only some of the areas in which future developments are possible. 

PMID- 24890886
TI  - Rearing in natural and recovering tidal wetlands enhances growth and life-history
      diversity of Columbia Estuary tributary coho salmon Oncorhynchus kisutch
      population.
AB  - This study provides evidence of the importance of tributary tidal wetlands to
      local coho salmon Oncorhynchus kisutch populations and life-history diversity.
      Subyearling and, to a lesser extent, yearling O. kisutch life histories utilized
      various estuary habitats within the Grays River, a tidal freshwater tributary of
      the Columbia River estuary, including restoring emergent wetlands and natural
      forested wetlands. Migration timing data, size distributions, estuary residence
      and scale patterns suggest a predominance of subyearling migrant life histories,
      including several that involve extended periods of estuary rearing. Estuarine
      rearing subyearling O. kisutch exhibited the greatest overall growth rates; the
      highest growth rates were seen in fish that utilized restoring emergent wetlands.
      These results contrast with studies conducted in the main-stem Columbia River
      estuary, which captured few O. kisutch, of which nearly all were hatchery-origin
      yearling smolts. Restoration and preservation of peripheral and tributary wetland
      habitats, such as those in the Grays River, could play an important role in the
      recovery of natural O. kisutch populations in the Columbia River and elsewhere. 

PMID- 24890885
TI  - A nonsense loss-of-function mutation in PCSK1 contributes to dominantly inherited
      human obesity.
AB  - BACKGROUND: A significant proportion of severe familial forms of obesity remain
      genetically elusive. Taking advantage of our unique cohort of multigenerational
      obese families, we aimed to assess the contribution of rare mutations in 29
      common obesity-associated genes to familial obesity, and to evaluate in these
      families the putative presence of nine known monogenic forms of obesity. METHODS:
      Through next-generation sequencing, we sequenced the coding regions of 34 genes
      involved in polygenic and/or monogenic forms of obesity in 201 participants (75
      normal weight individuals, 54 overweight individuals and 72 individuals with
      obesity class I, II or III) from 13 French families. In vitro functional analyses
      were performed to investigate the mutation PCSK1-p.Arg80* which was identified in
      a family. RESULTS: A novel heterozygous nonsense variant in PCSK1 (p.Arg80*),
      encoding a propeptide truncated to less than two exons (out of 14), was found to
      co-segregate with obesity in a three-generation family. We demonstrated that this
      mutation inhibits PCSK1 enzyme activity and that this inhibition most likely does
      not involve a strong physical interaction. Furthermore, both mutations PCSK1
      p.Asn180Ser and POMC-p.Phe144Leu, which had previously been reported to be
      associated with severe obesity, were also identified in this study, but did not
      co-segregate with obesity. Finally, we did not identify any rare mutations co
      segregating with obesity in common obesity susceptibility genes, except for CADM2
      and QPCTL, where we found two novel variants (p.Arg81His and p.Leu98Pro,
      respectively) in three obese individuals. CONCLUSIONS: We showed for the first
      time that a nonsense mutation in PCSK1 was likely to cause dominantly inherited
      human obesity, due to the inhibiting properties of the propeptide fragment
      encoded by the null allele. Furthermore, the present family sequencing design
      challenged the contribution of previously reported mutations to monogenic or at
      least severe obesity.

PMID- 24890887
TI  - [Respiratory syncitial virus in immunocompromised patients in a pediatric
      hospital: 5 years experience].
AB  - INTRODUCTION: Respiratory syncytial virus (RSV) infection is associated with an
      increase in morbidity and mortality in immunocompromised hosts. METHODS: A
      description is presented of all cases of RSV infection in immunocompromised
      pediatric patients in Hematology and Oncology and Immunodeficiency Units between
      2008 and 2012. RESULTS: Nineteen patients were diagnosed with RSV infection. Nine
      patients required in-patient care and 2 required Pediatric Intensive Care Unit.
      Five patients were treated with specific therapy (ribavirin +/- palivizumab). No
      deaths occurred in the study period. CONCLUSION: RSV infection may be severe in
      immunocompromised pediatric patients.

PMID- 24890888
TI  - [Respiratory treatments in neuromuscular disease].
AB  - In a previous article, a review was presented of the respiratory pathophysiology
      of the patient with neuromuscular disease, as well as their clinical evaluation
      and the major complications causing pulmonary deterioration. This article
      presents the respiratory treatments required to preserve lung function in
      neuromuscular disease as long as possible, as well as in special situations
      (respiratory infections, spinal curvature surgery, etc.). Special emphasis is
      made on the use of non-invasive ventilation, which is changing the natural
      history of many of these diseases. The increase in survival and life expectancy
      of these children means that they can continue their clinical care in adult
      units. The transition from pediatric care must be an active, timely and
      progressive process. It may be slightly stressful for the patient before the
      adaptation to this new environment, with multidisciplinary care always being
      maintained. 

PMID- 24890889
TI  - [Is the wait-and-see approach in Gorham syndrome a therapeutic option?].

PMID- 24890890
TI  - [Hypertrophic osteoarthropathy and Hodgkin's disease].

PMID- 24890891
TI  - [Mouth ulcers as a clinical sign in a case cyclic neutropenia with an ELA 2 gene
      mutation].

PMID- 24890892
TI  - Effect of long-term GH treatment in a patient with CHARGE association.
AB  - CHARGE association is characterized by ocular Coloboma, Heart malformations,
      choanal Atresia, Retardation of growth and development, Genital abnormalities and
      inner and external Ear abnormalities. Growth failure is a frequent find mainly
      associated with feeding difficulties or systemic diseases. To date, GH deficiency
      has been reported in only few patients with CHARGE association however long-term
      effects of GH treatment, up to final height, have never been reported. We
      describe a patient with CHARGE association and GH deficiency treated with GH from
      the age of 3 years and 10 months up to adult height.

PMID- 24890893
TI  - Expression of breast cancer resistance protein in peripheral T cell subsets from
      HIV-1-infected patients with antiretroviral therapy.
AB  - The aim of the present study was to investigate the expression of breast cancer
      resistance protein (BCRP) in peripheral T cell subsets of human immunodeficiency
      virus 1 (HIV-1)-infected patients, and to analyze the association between the
      levels of BCRP expression and disease progression in HIV-1 infection. Peripheral
      blood mononuclear cells (PBMCs) were obtained from HIV-1-infected patients
      (n=118), including 92 patients with antiretroviral therapy (ART) and 26 patients
      without a history of ART. Control samples from 30 healthy donors were also
      analyzed. The expression levels of BCRP in T cells were evaluated by flow
      cytometry. A high inter-individual variability was observed in CD4+ and CD8+ T
      cells in the HIV-1-infected patients and healthy donors; however, the analyzed
      expression levels of BCRP were significantly higher in the HIV-1-infected group
      with ART than those in the group with no history of ART (P<0.01). Furthermore,
      the frequency of BCRP-expressing T cells was inversely correlated with CD4+ and
      CD8+ T cell counts in HIV-1-infected patients with ART. The results suggested
      that BCRP expression varied among HIV-1-infected patients and healthy donors but
      was significantly higher in HIV-1 patients undergoing ART. In conclusion, the
      present study suggested that overexpression of BCRP may be involved in disease
      progression of the HIV-1 infection and may participate in drug resistance to ART,
      thus contributing to the failure of highly active ART in HIV-1 therapeutics. 

PMID- 24890894
TI  - What is the malignancy risk for atypia of undetermined significance? Three years'
      experience at a university hospital in Turkey.
AB  - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC)
      provides uniform diagnostic terminology for communication between pathologists
      and clinicians. Each diagnostic category is associated with a specific risk of
      malignancy and a recommendation for its management. The indeterminate diagnostic
      categories of atypia of undetermined significance/follicular lesion of
      undetermined significance (AUS/FLUS) present a major challenge for both
      pathologists and clinicians. We report our institution's 3 years' experience with
      the AUS/FLUS category and follow-up of these patients. METHODS: A retrospective
      analysis was conducted for all thyroid fine-needle aspirations (FNAs) between
      July 2010 and July 2013. During this period, 9242 nodules from 4916 patients were
      reported according to the BSRTC guidelines. We adopted the AUS terminology in our
      practice to refer to both AUS, and FLUS. RESULTS: Of the 4916 patients, 347 (7%)
      were diagnosed as AUS. The malignancy risk for patients who underwent surgical
      resection after initial diagnosis of AUS was 22.8%, whereas that for patients who
      underwent a second FNA and surgical resection was 36%. When we included patients
      with second FNA and without surgery, the malignancy risk was 15.7%. CONCLUSIONS:
      The malignancy risk for AUS reported in the present study is consistent with
      those reported previously and is higher than those anticipated according to the
      Bethesda System. This supports that a multimodal approach (clinical, radiologic,
      and cytopathologic) is necessary for the management of thyroid nodules diagnosed
      as AUS. Therefore, we suggest that the recommendation for repeat FNA following an
      initial diagnosis of AUS should be based on a multimodal approach for each
      particular patient.

PMID- 24890895
TI  - Confinement of CuII -phthalocyanine in a bioinspired hybrid nanoparticle
      assembled structure yields selective and stable epoxidation catalysts.
AB  - Herein, we demonstrate that a bioinspired assembly of silica nanoparticles with
      polyamines as structure-directing agents similar to that known for the
      biosilicification of diatoms can pave the way for the efficient encapsulation of
      sulfonated copper-phthalocyanine in a hybrid microcapsule structure, in which the
      organic component provides a capable environment for its catalytic activity in
      epoxidation reactions and the nanoassembled structure imparts stability. 

PMID- 24890896
TI  - The impact of a large-scale quality improvement programme on work engagement:
      preliminary results from a national cross-sectional-survey of the 'Productive
      Ward'.
AB  - BACKGROUND: Quality improvement (QI) Programmes, like the Productive Ward:
      Releasing-time-to-care initiative, aim to 'engage' and 'empower' ward teams to
      actively participate, innovate and lead quality improvement at the front line.
      However, little is known about the relationship and impact that QI work has on
      the 'engagement' of the clinical teams who participate and vice-versa. OBJECTIVE:
      This paper explores and examines the impact of a large-scale QI programme, the
      Productive Ward, on the 'work engagement' of the nurses and ward teams involved.
      DESIGN/METHODS: Using the Utrecht Work Engagement Scale (UWES), we surveyed,
      measured and analysed work engagement in a representative test group of hospital
      based ward teams who had recently commenced the latest phase of the national
      'Productive Ward' initiative in Ireland and compared them to a control group of
      similar size and matched (as far as is possible) on variables such as ward size,
      employment grade and clinical specialty area. RESULTS: 338 individual datasets
      were recorded, n=180 (53.6%) from the Productive Ward group, and n=158 (46.4%)
      from the control group; the overall response rate was 67%, and did not differ
      significantly between the Productive Ward and control groups. The work engagement
      mean score (+/-standard deviation) in the Productive group was 4.33(+/-0.88), and
      4.07(+/-1.06) in the control group, representing a modest but statistically
      significant between-group difference (p=0.013, independent samples t-test).
      Similarly modest differences were observed in all three dimensions of the work
      engagement construct. Employment grade and the clinical specialty area were also
      significantly related to the work engagement score (p<0.001, general linear
      model) and (for the most part), to its components, with both clerical and nurse
      manager grades, and the elderly specialist areas, exhibiting substantially higher
      scores. CONCLUSIONS: The findings demonstrate how QI activities, like those
      integral to the Productive Ward programme, appear to positively impact on the
      work engagement (the vigour, absorption and dedication) of ward-based teams. The
      use and suitability of the UWES as an appropriate measure of 'engagement' in QI
      interventions was confirmed. The engagement of nurses and front-line clinical
      teams is a major component of creating, developing and sustaining a culture of
      improvement.

PMID- 24890897
TI  - A light shines on melanoma metastagenesis.

PMID- 24890898
TI  - Emotional processing and brain activity in youth at high risk for alcoholism.
AB  - BACKGROUND: Even in the absence of heavy alcohol use, youth with familial
      alcoholism (family history positive [FHP]) exhibit atypical brain functioning and
      behavior. Although emotional and cognitive systems are affected in alcohol use
      disorders (AUDs), little attention has focused on whether brain and behavior
      phenotypes related to the interplay between affective and executive functioning
      may be a premorbid risk factor for the development of AUDs in FHP youth. METHODS:
      Twenty-four FHP and 22 family history negative (FHN) 12- to 16-year-old
      adolescents completed study procedures. After exclusion of participants with
      clinically significant depressive symptoms and those who did not meet performance
      criteria during an Emotional Go-NoGo task, 19 FHP and 17 FHN youth were included
      in functional magnetic resonance imaging (fMRI) analyses. Resting state
      functional connectivity MRI, using amygdalar seed regions, was analyzed in 16 FHP
      and 18 FHN youth, after exclusion of participants with excessive head movement.
      RESULTS: fMRI showed that brain activity in FHP youth, compared with FHN peers,
      was reduced during emotional processing in the superior temporal cortex, as well
      as during cognitive control within emotional contexts in frontal and striatal
      regions. Group differences in resting state amygdalar connectivity were seen
      bilaterally between FHP and FHN youth. In FHP youth, reduced resting state
      synchrony between the left amygdala and left superior frontal gyrus was related
      to poorer response inhibition, as measured during the fMRI task. CONCLUSIONS: To
      our knowledge, this is the first study to examine emotion-cognition interactions
      and resting state functional connectivity in FHP youth. Findings from this
      research provide insight into neural and behavioral phenotypes associated with
      emotional processing in familial alcoholism, which may relate to increased risk
      of developing AUDs.

PMID- 24890899
TI  - Educational challenges to the health care professional in heart failure care.
AB  - The purpose of this review is to discuss the educational challenges faced by
      health care professionals in the care and management of patients with heart
      failure (HF). Self-care is a vital component in HF management, and promotion of
      self-care through education is a fundamental aspect of patient-centered care and
      supports patients' right to autonomy. The ultimate goal is not simply to convey
      knowledge, but to promote patients' understanding and to enhance their self-care
      skills by assuming an active role in their care. As such, health care
      professionals are confronted with a number of patient-related issues as they
      strive to provide high-quality education. Beyond assessing patients' individual
      information needs and preferences, they are tasked with addressing several
      obstacles that impede patients' ability to engage in self-care. Factors such as
      cognitive impairment and low health literacy have a major impact on patients'
      ability to understand, absorb, and recall information. Moreover, the existence of
      negative beliefs, which are strong determinants of patients' attitudes towards
      their disease and treatment, may also influence their response to educational
      messages. Health care professionals must not only identify and overcome these
      obstacles, but they must act effectively within the limitations of their working
      environment and of the health care system. 

PMID- 24890900
TI  - How should we advise heart failure patients on exercise and what should we tell
      them?
AB  - The article discusses the problem of motivating and encouraging patients with
      heart failure to perform regular exercise training. Firstly, the benefits of
      exercise training are presented, and rational and convincing arguments justifying
      its implementation in heart failure patients are provided. Secondly, the issue of
      overcoming barriers to exercise training implementation is considered. Finally,
      the role of the medical team and family members in supporting patients with heart
      failure in long-term adherence to recommendations is defined and analyzed. In
      addition, the article presents various ways of performing exercise training
      easily. 

PMID- 24890901
TI  - Hyperglycemia in acute heart failure: an opportunity to intervene?
AB  - In patients with acute heart failure (AHF) syndromes, little data are so far
      available on the relation between glucose values and insulin resistance and
      mortality, both in the short and long term. The present review is aimed at
      summarizing available evidence on the prognostic role of hyperglycemia in acute
      heart failure syndromes. Despite the fact that glucose values are widely
      measured, inexpensive, and easy to interpret, hyperglycemia in AHF patients still
      appears to be (or at least to have been) a neglected factor. Scarce information
      is available on incidence of admission hyperglycemia (especially in nondiabetic
      AHF patients) and data on in-hospital and discharge glucose values are lacking.
      Overall, the scarcity of data and the unanswered questions conjure up the need
      for trials investigating the clinical and prognostic role of glucose
      abnormalities (hyperglycemia and acute insulin resistance) on admission and
      during hospital stay in AHF patients. Preliminary evidence suggests that
      hyperglycemia is an important prognostic factor in AHF; however, whether
      targeting hyperglycemia via an aggressive versus permissive glycemic management
      strategy influences AHF outcomes remains unknown. 

PMID- 24890903
TI  - Hidradenitis suppurativa fulminans: a clinically distinct phenotype?

PMID- 24890902
TI  - Cardiohepatic syndrome: liver injury in decompensated heart failure.
AB  - Heart failure (HF) is a major healthcare concern. Acute HF carries a high
      mortality and a high rehospitalisation rate. HF has a variety of detrimental
      effects on other organs. In recent years, the interactions between heart failure
      and the kidney have been the subject of significant investigations; this
      interaction, defined as "cardiorenal syndrome", is relatively well characterized.
      We describe here another interaction between the heart and the liver, the
      "cardiohepatic syndrome", in acute HF patients. Recent publications have shown
      that liver function test (LFT) abnormalities were associated with AHF severity.
      Clinical signs of systemic congestion were found to be associated with
      cholestasis, when signs of hypoperfusion were associated with liver cytolysis.
      Defining the LFT profile in AHF may play an important role in the future
      management of AHF patients. 

PMID- 24890904
TI  - Quality of life in older patients with chronic obstructive pulmonary disease
      (COPD) in Hong Kong: a case-control study.
AB  - PURPOSE: To date, there have been few studies examining quality of life (QOL) in
      older patients with chronic obstructive pulmonary disease (COPD) in China. The
      aim of the study was to assess QOL in Chinese older patients with COPD and
      explore its demographic and clinical correlates. DESIGN AND METHODS: Case-control
      study of 142 outpatients with COPD and 218 matched control subjects without COPD.
      COPD patients were recruited from a prospective study sample hospitalized in Hong
      Kong for acute COPD exacerbation (>= 2 major COPD symptoms or > 1 major + minor
      COPD symptoms for >= 2 consecutive days). Controls were recruited from social
      centers in Hong Kong. Activity of daily living was assessed with the Instrumental
      Activities of Daily Living Scale (IADL), life events were evaluated with the Life
      Event Scale, depressive disorders were diagnosed using the Geriatric Depression
      Scale (GDS), and QOL was measured using the Medical Outcomes Study Short Form-12
      (SF-12) and St. George's Respiratory Questionnaire (SGRQ). FINDINGS: Compared to
      controls, patients had significantly lower scores in the physical (PCS score),
      but not in the mental (MCS score) QOL domain. Multivariate analyses showed that
      more hospitalizations in the past year significantly contributed to higher PCS
      score (p = .03), while higher GDS total score contributed to lower MCS score (p =
      .003). Severe and very severe COPD, more physical illnesses, and higher IADL
      total score each independently contributed to higher SGRQ total score, explaining
      40.0% of the variance (p < .001). PRACTICE IMPLICATIONS: Our results suggest that
      therapeutic and psychosocial interventions alleviating depressive symptoms,
      severe COPD, comorbidities, and improving IADL in Chinese patients with COPD are
      likely of considerable benefit for improving QOL in patients with COPD.

PMID- 24890905
TI  - Comprehensive analysis of pharmaceutical products using simultaneous mixed-mode
      (ion-exchange/reversed-phase) and hydrophilic interaction liquid chromatography.
AB  - Liquid chromatographic assays were developed using a mixed-mode column coupled in
      sequence with a hydrophilic interaction liquid chromatography column to allow the
      simultaneous comprehensive analysis of inorganic/organic anions and cations,
      active pharmaceutical ingredients, and excipients (carbohydrates). The approach
      utilized dual sample injection and valve-mediated column switching and was based
      upon a single high-performance liquid chromatography gradient pump. The
      separation consisted of three distinct sequential separation mechanisms, namely,
      (i) ion-exchange, (ii) mixed-mode interactions under an applied dual gradient
      (reversed-phase/ion-exchange), and (iii) hydrophilic interaction chromatography.
      Upon first injection, the Scherzo SS C18 column (Imtakt) provided resolution of
      inorganic anions and cations under isocratic conditions, followed by a dual
      organic/salt gradient to elute active pharmaceutical ingredients and their
      respective organic counterions and potential degradants. At the top of the mixed
      mode gradient (high acetonitrile content), the mobile phase flow was switched to
      a preconditioned hydrophilic interaction liquid chromatography column, and the
      standard/sample was reinjected for the separation of hydrophilic carbohydrates,
      some of which are commonly known excipients in drug formulations. The approach
      afforded reproducible separation and resolution of up to 23 chemically diverse
      solutes in a single run. The method was applied to investigate the composition of
      commercial cough syrups (Robitussin(r)), allowing resolution and determination of
      inorganic ions, active pharmaceutical ingredients, excipients, and numerous well
      resolved unknown peaks. 

PMID- 24890906
TI  - Profiling of the secretome of human cancer cells: preparation of supernatant for
      proteomic analysis.
AB  - Secretomic analysis requires removal of serum proteins from cell-culture media.
      We evaluate the proteins washed from cells prepared in bovine serum-supplemented
      medium. PBS and serum-free-medium (SFM) were the washing solutions. A Bradford
      assay was used for total protein concentration and a 1D gel and LC-MS/MS, to
      assign the protein to human or bovine origin. For both wash solutions, all bovine
      protein had been removed by the third wash, without compromising the number of
      living cells. Further washes reduced the number of living cells, especially when
      using PBS. Proteomic analysis of wash supernatant showed that SFM induced greater
      lysis of dead cells. Three washes were sufficient to minimize the effects on cell
      viability, while still removing serum proteins. Washing in SFM resulted in
      contamination of the wash supernatant with lysed dead cell proteins. Washed cells
      were incubated in SFM and exposed to ionizing radiation. Analysis of the
      supernatant showed an increase in human cytoplasmic, plasma membrane, and nuclear
      protein following irradiation. Secreted proteins were also detected, but in
      smaller quantities. The significance of these findings extend to in vitro studies
      of bystander phenomena, since the proteins of lysed dead cells may participate in
      driving bystander responses.

PMID- 24890907
TI  - Challenges of thermal nociceptive threshold testing in the donkey.
AB  - OBJECTIVE: To evaluate a thermal nociceptive threshold (TNT) testing device in
      the donkey, and the influence of potential confounding factors on TNTs. ANIMALS:
      Two groups (Group 1 and Group 2) of eight castrated male donkeys aged 4-9 years,
      weighing 105-170 kg. METHODS: TNTs were measured by heating a thermal probe on
      skin until an end-point behaviour (threshold temperature) or a cut-out
      temperature (51  degrees C) was reached. The withers and the dorsal aspect of the
      distal limb were used as sites for TNT testing. The effects on TNT of different
      confounding factors: the limb tested; rate of heating; and ambient temperature
      were evaluated. Data were analyzed using general linear models, and Mann-Whitney
      tests, p < 0.05 was considered significant. RESULTS: End-point behaviours (skin
      twitch or donkey looking at test device) when the thermal probe heated the
      withers were observed in approximately half of tests. TNT was (mean +/- SD) 46.8
      +/- 2.85  degrees C. Subsequently the limb was evaluated as the test site in
      Group 1 followed by Group 2 donkeys; end-point behaviour being a foot-lift. In
      Group 1, 72% of tests ended in an end-point behaviour but the response rate was
      lower in Group 2 (20%), although TNTs were similar [(47.6 +/- 3.3) and (47.3 +/-
      3.0)  degrees C respectively] for responding animals. Rate of heating, ambient
      temperature and laterality (right or left) did not affect thresholds, but mean
      TNT was significantly higher in the forelimb (48.5 +/- 2.8  degrees C) than the
      hind limb (47.4 +/- 2.8  degrees C) (p = 0.012). CONCLUSIONS: When a thermal
      probe cut-out temperature of 51  degrees C was used in TNT testing in the donkey
      a high proportion of tests did not produce an identifiable end point behaviour.
      Higher cut-out temperatures damaged the skin. Under these conditions, thermal
      nociceptive threshold testing appears not be an appropriate analgesiometry
      technique in the donkey. CLINICAL RELEVANCE: TNT testing under these conditions
      is not suitable form of analgesiometry for donkeys.

PMID- 24890908
TI  - Continuous flow photochemistry.
AB  - Due to the narrow width of tubing/reactors used, photochemistry performed in
      micro- and mesoflow systems is significantly more efficient than when performed
      in batch due to the Beer-Lambert Law. Owing to the constant removal of product
      and facility of flow chemical scalability, the degree of degradation observed is
      generally decreased and the productivity of photochemical processes is increased.
      In this Personal Account, we describe a wide range of photochemical
      transformations we have examined using both visible and UV light, covering
      cyclizations, intermolecular couplings, radical polymerizations, as well as
      singlet oxygen oxygenations. 

PMID- 24890909
TI  - Ibrutinib rash in a patient with 17p del chronic lymphocytic leukemia.

PMID- 24890910
TI  - Improving Aboriginal maternal and infant health services in the 'Top End' of
      Australia; synthesis of the findings of a health services research program aimed
      at engaging stakeholders, developing research capacity and embedding change.
AB  - BACKGROUND: Health services research is a well-articulated research methodology
      and can be a powerful vehicle to implement sustainable health service reform.
      This paper presents a summary of a five-year collaborative program between
      stakeholders and researchers that led to sustainable improvements in the
      maternity services for remote-dwelling Aboriginal women and their infants in the
      Top End (TE) of Australia. METHODS: A mixed-methods health services research
      program of work was designed, using a participatory approach. The study area
      consisted of two large remote Aboriginal communities in the Top End of Australia
      and the hospital in the regional centre (RC) that provided birth and tertiary
      care for these communities. The stakeholders included consumers, midwives,
      doctors, nurses, Aboriginal Health Workers (AHW), managers, policy makers and
      support staff. Data were sourced from: hospital and health centre records;
      perinatal data sets and costing data sets; observations of maternal and infant
      health service delivery and parenting styles; formal and informal interviews with
      providers and women and focus groups. Studies examined: indicator sets that
      identify best care, the impact of quality of care and remoteness on health
      outcomes, discrepancies in the birth counts in a range of different data sets and
      ethnographic studies of 'out of hospital' or health centre birth and parenting. A
      new model of maternity care was introduced by the health service aiming to
      improve care following the findings of our research. Some of these improvements
      introduced during the five-year research program of research were evaluated.
      RESULTS: Cost effective improvements were made to the acceptability, quality and
      outcomes of maternity care. However, our synthesis identified system-wide
      problems that still account for poor quality of infant services, specifically,
      unacceptable standards of infant care and parent support, no apparent
      relationship between volume and acuity of presentations and staff numbers with
      the required skills for providing care for infants, and an 'outpatient' model of
      care. Services were also characterised by absent Aboriginal leadership and
      inadequate coordination between remote and tertiary services that is essential to
      improve quality of care and reduce 'system-introduced' risk. CONCLUSION: Evidence
      informed redesign of maternity services and delivery of care has improved
      clinical effectiveness and quality for women. However, more work is needed to
      address substandard care provided for infants and their parents.

PMID- 24890911
TI  - Rehabilitation in obesity with comorbidities: a consensus document from experts
      of the Italian Society of Physical and Rehabilitation Medicine (SIMFER), the
      Italian Society of Obesity (SIO) and the Italian Society of Eating Disorders
      (SISDCA).
AB  - Severe obesity is a chronic disease associated with medical and psychosocial
      comorbidity causing disability and poor quality of life that represents a social
      and economic burden for the National Health Systems worldwide. The Italian
      Society of Physical and Rehabilitation Medicine (SIMFER), the Italian Society of
      Obesity (SIO) and the Italian Society of Eating Disorders (SISDCA) have joined in
      a panel of experts to discuss a consensus document on the requisites of
      rehabilitation units devoted to patients affected by severe obesity with
      comorbidities. The main recommendations of the consensus document are the
      following: (1) the management of severe obesity should be characterized by the
      integration of nutritional, physical/functional rehabilitation, psycho
      educational, and rehabilitative nursing interventions; (2) the intensity of the
      rehabilitative interventions should depend on the level of severity and
      comorbidities, frailty of the psychic status, degree of disability and quality of
      life of the patient; (3) the rehabilitative approach should be multidisciplinary
      and integrated in relation to the clinical complexity of obesity; (4) the
      estimated need for multidimensional rehabilitation of severe obesity is 1 bed per
      every 1,000 patients and of 4 beds in rehabilitative day-care ward every 1,000
      patients suffering from severe obesity with comorbidities. 

PMID- 24890913
TI  - Editorial: industrial biotechnology - technologies and methods for rapid process
      development.

PMID- 24890912
TI  - Effect of dronabinol therapy on physical activity in anorexia nervosa: a
      randomised, controlled trial.
AB  - PURPOSE: The level of physical activity is inappropriately high in up to 80% of
      the patients suffering of anorexia nervosa (AN), as a result of conscious efforts
      to lose weight, affect regulation and biological adaptive changes to starvation
      induced by hypothermia and neuroendocrine mechanisms. The purposes of this paper
      were to (1) assess the effect of dronabinol-a synthetic cannabinoid agonist-on
      physical activity in patients with chronic and stable AN, and to (2) unravel the
      role of leptin and cortisol in this process. METHODS: This prospective,
      randomised, double-blind, crossover study was conducted at a specialised care
      centre for eating disorders. Twenty-four adult women with AN of at least 5-year
      duration received either the dronabinol-placebo or placebo-dronabinol sequence.
      Physical activity was monitored during the fourth week of each intervention. Body
      weight, leptin and urinary free cortisol excretion were measured repeatedly
      during the trial. Changes in behavioural dimensions related to AN were assessed
      by Eating Disorder Inventory-2. RESULTS: The total duration of physical activity
      did not change, while its average intensity increased by 20% (P = 0.01) during
      dronabinol therapy, resulting in an increased energy expenditure with 68.2
      kcal/day (P = 0.01) above placebo. CONCLUSIONS: This randomised, double-blind
      study revealed that cannabinoid agonist treatment was associated with a modest
      increase in physical activity in adult women with severe and longstanding AN.
      Additionally, we detected a strong relationship between the circulating levels of
      leptin and physical activity in these chronically undernourished patients.

PMID- 24890919
TI  - Revealing the fine details of functionalized silica surfaces by solid-state NMR
      and adsorption isotherm measurements: the case of fluorinated stationary phases
      for liquid chromatography.
AB  - The structural and chromatographic characterization of two novel fluorinated
      mesoporous materials prepared by covalent reaction of 3
      (pentafluorophenyl)propyldimethylchlorosilane and
      perfluorohexylethyltrichlorosilane with 2.5 MUm fully porous silica particles is
      reported. The adsorbents were characterized by solid state (29)Si, (13)C, and
      (19)F NMR spectroscopy, low-temperature nitrogen adsorption, elemental analysis
      (C and F), and various chromatographic measurements, including the determination
      of adsorption isotherms. The structure and abundance of the different organic
      surface species, as well as the different silanol types, were determined. In
      particular, the degree of so-called horizontal polymerization, that is, Si-O-Si
      bridging parallel to the silica surface due to the reaction, under "quasi-dry"
      conditions, of trifunctional silanizing agents with the silica surface was
      quantified. Significant agreement was found between the information provided by
      solid-state NMR, elemental analysis, and excess isotherms regarding the amount of
      surface residual silanol groups, on the one hand, and the degree of surface
      functionalization, on the other. Finally, the kinetic performance of the
      fluorinated materials as separation media for applications in near-ultrahigh
      performance liquid chromatography was evaluated. At reduced velocities of about
      5.5 (ca. 600 bar backpressure at room temperature) with 3 mm diameter columns and
      toluene as test compound, reduced plate heights on the order of 2 were obtained
      on columns of both adsorbents.

PMID- 24890918
TI  - Exploring the substrate range of wild-type aminoacyl-tRNA synthetases.
AB  - We tested the substrate range of four wild-type E. coli aminoacyl-tRNA
      synthetases (AARSs) with a library of nonstandard amino acids (nsAAs). Although
      these AARSs could discriminate efficiently against the other canonical amino
      acids, they were able to use many nsAAs as substrates. Our results also show that
      E. coli tryptophanyl-tRNA synthetase (TrpRS) and tyrosyl-tRNA synthetase have
      overlapping substrate ranges. In addition, we found that the nature of the
      anticodon sequence of tRNA(Trp) altered the nsAA substrate range of TrpRS; this
      implies that the sequence of the anticodon affects the TrpRS amino acid binding
      pocket. These results highlight again that inherent AARS polyspecificity will be
      a major challenge in the aim of incorporating multiple different amino acids site
      specifically into proteins. 

PMID- 24890920
TI  - A mimic of first dorsal interosseus atrophy revealed by ultrasound study.

PMID- 24890921
TI  - Normal nerve conduction with an abnormal ultrasound: a separate group of CTS?

PMID- 24890922
TI  - Sun protection among Spanish beachgoers: knowledge, attitude and behaviour.
AB  - This study aims to investigate the level of awareness on the risks related to sun
      exposure, attitude towards sun protection and sun protection behaviour in Spanish
      beachgoers. During the summer of 2009, trained assistants conducted a structured
      interview with 630 sunbathers at the beaches of Valencia, Spain, via
      administrating a questionnaire including the following: (a) general data (age,
      gender, education, profession), (b) "knowledge" and "attitude" items and (c) self
      assessed sun sensitivity, sun exposure and sun protection characteristics. The
      health belief model was used to evaluate factors that may influence on engaging
      healthy behaviour. The median age was 30 (2-82) years; the M/F ratio was 0.60.
      Despite the widespread regular ("often" or "always", 80%) use of high (>15) sun
      protective factor sunscreens, current recommendations on sun protection were not
      regularly followed, and a history of sunburns is very common (70%). At
      multivariate analysis, female gender, age, fair hair, freckles, all-day use of
      sunscreens and wearing sunglasses were independent factors associated with having
      sunburn history. A high knowledge and a fairly good attitude emerged (median
      scores, 6/7 and 22/30, respectively). Age class (p = 0.032), educational level (p
      < 0.0001), sunscreen use (p = 0.048) and adequate timing of the first application
      of sunscreens (p = 0.015) were predictors of awareness, while factors associated
      with a more favourable attitude were educational level (p < 0.0001) and regular
      use of hats (p = 0.001). Wrong beliefs mainly concern sunscreens (false safety);
      the attractiveness of a tanned look is the main unfavourable attitude. Physical
      and motivational barriers are common (80%). The findings by highlighting
      constitutional and psychosocial factors involved in unhealthy behaviour provide
      useful information to promote sun-safe interventions in this population.

PMID- 24890923
TI  - Therapeutic plasma exchange in a patient with erythropoietic protoporphyria
      status post orthothopic liver transplantation as a bridge to hematopoietic stem
      cell transplantation.

PMID- 24890924
TI  - Prospective study of ultrasound-guided fine-needle aspiration cytology and
      sentinel node biopsy in the staging of clinically negative T1 and T2 oral cancer.
AB  - BACKGROUND: The purpose of this study was to compare sentinel node biopsy (SNB)
      and ultrasound-guided fine-needle aspiration cytology (FNAC) for preoperative
      evaluation of the N0 neck in T1 to T2 oral cavity squamous cell carcinoma (SCC).
      METHODS: Fifty-one consecutive patients with T1 to T2 N0 oral cavity SCC were
      included in this study. Preoperative ultrasound was performed in all patients.
      Ultrasound-guided FNAC was performed in patients in whom the ultrasound result
      was reported as indeterminate or positive. SNB was done in all patients followed
      by elective neck dissection (END). Histopathology of END was considered as the
      gold standard for all statistical analysis. RESULTS: The incidence of occult
      metastasis was 26.4%. The sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) were 71.4%, 100%, 100%, and 90.2% for
      SNB and 14.3%, 100%, 100%, and 76.5% for ultrasound-guided FNAC. CONCLUSION:
      Ultrasound-guided FNAC lacked sufficient accuracy to detect occult metastases.
      SNB is a reliable method to detect occult metastasis that has potential to
      replace END.

PMID- 24890925
TI  - Abnormal differentiation of intestinal epithelium and intestinal barrier
      dysfunction in diabetic mice associated with depressed Notch/NICD transduction in
      Notch/Hes1 signal pathway.
AB  - Proliferative change and intestinal barrier dysfunction in intestinal mucosa of
      diabetes have been described, but the differentiation characteristics of
      intestinal epithelial cells (IECs) and the mechanisms in the IECs development
      remain unclear. To explore the intestinal epithelial constitution patterns and
      barrier function, the diabetic mouse model was induced by streptozotocin. Tight
      junctions between IECs were significantly damaged and the serum level of D
      lactate was raised in diabetic mice (P < 0.05). The expression of Zo1 and Ocln in
      the small intestine of diabetic mice were lower, while the markers for absorptive
      cell (SI) and Paneth cell (Lyz1) were significantly higher than in control mice
      (P < 0.05). The expression of Msi1, Notch1, and Dll1 in small intestine gradually
      increased throughout the course of hyperglycemia in diabetic mice (P < 0.05).
      However, the expression of NICD, RBP-jkappa, Math1, and Hes1 had a reverse trend
      compared with Msi1 and Notch1. Intestinal absorptive cells and Paneth cells had a
      high proliferation rate in diabetic mice. However, the intestinal barrier
      dysfunction associated with the decreased expressions of Zo1 and Ocln was
      detected throughout hyperglycemia. In conclusion, downregulation of Notch/Hes1
      signal pathway caused by depressed Notch/NICD transduction is associated with the
      abnormal differentiation of IECs and intestinal barrier dysfunction in diabetic
      mice. 

PMID- 24890926
TI  - Equipped: overcoming barriers to change to improve quality of care (theories of
      change).

PMID- 24890927
TI  - Regulation of immune responses by proton channels.
AB  - The identification of the HVCN1 gene, encoding the only mammalian voltage-gated
      proton channel, prompted a number of studies on how proton channels affect
      cellular functions. As their expression is mainly restricted to immune cells, it
      is not surprising that proton channels regulate different aspects of immune
      responses. In this review, I will examine the current knowledge of voltage-gated
      proton channels in both innate and adaptive responses and assess the remaining
      outstanding questions.

PMID- 24890929
TI  - Fasciitis ossificans of the breast.

PMID- 24890928
TI  - How should periods without social interaction be scheduled? Children's preference
      for practical schedules of positive reinforcement.
AB  - Several studies have shown that children prefer contingent reinforcement (CR)
      rather than yoked noncontingent reinforcement (NCR) when continuous reinforcement
      is programmed in the CR schedule. Preference has not, however, been evaluated for
      practical schedules that involve CR. In Study 1, we assessed 5 children's
      preference for obtaining social interaction via a multiple schedule (periods of
      fixed-ratio 1 reinforcement alternating with periods of extinction), a briefly
      signaled delayed reinforcement schedule, and an NCR schedule. The multiple
      schedule promoted the most efficient level of responding. In general, children
      chose to experience the multiple schedule and avoided the delay and NCR
      schedules, indicating that they preferred multiple schedules as the means to
      arrange practical schedules of social interaction. In Study 2, we evaluated
      potential controlling variables that influenced 1 child's preference for the
      multiple schedule and found that the strong positive contingency was the primary
      variable. 

PMID- 24890931
TI  - Diagnosis of loss of consciousness: when art meets science.

PMID- 24890930
TI  - Outcomes after resective epilepsy surgery in patients over 50 years of age in
      Sweden 1990-2009--a prospective longitudinal study.
AB  - PURPOSE: Most epilepsy surgery candidates are young adults. Outcome reports after
      epilepsy surgery in patients >=50 years are few and varying. The aim of this
      study was to describe patient characteristics of older compared to younger adults
      and analyse seizure, complication and vocational outcomes in a large population
      based series. METHODS: We analysed data from the Swedish National Epilepsy
      Surgery Register for 1990-2009 for patients >=19 years at resective surgery who
      had completed two-year follow-up. Variables studied were seizure outcome, histo
      pathological diagnoses, complications and vocational outcome. Data from patients
      >=50 years and 19-49 years at surgery were compared. RESULTS: 558 Adults
      underwent resective epilepsy surgery 1990-2009 and had two-year follow-up. 12% of
      the adults (67 patients) were >=50 years at surgery. Patients >=50 had longer
      epilepsy duration, more often had mesial sclerosis and less often had
      neurodevelopmental tumours and cortical malformations. The proportion of seizure
      free patients at two-year follow-up did not differ between those >=50 and 19-49
      years (61% versus 61% seizure-free last year, 48% versus 43% completely seizure
      free since surgery), neither did the occurrence of major complications (3% in
      both groups). The vocational situation was mainly stable between baseline and two
      year follow-up in both groups, although older patients were less often employed
      than younger. CONCLUSION: 12% of adults in the Swedish series were >=50 years at
      epilepsy surgery. Seizure outcome was as good for older as for younger adults,
      and there was no difference in the occurrence of major complications. This
      constitutes important information in the presurgical counselling process.

PMID- 24890932
TI  - Pilomotor seizures: an autonomic semiology of limbic encephalitis?
AB  - PURPOSE: Ictal piloerection is an infrequent seizure semiology that is commonly
      overlooked as an ictal epileptic manifestation. Piloerection is considered to be
      principally caused by temporal lobe activity although frontal and hypothalamic
      seizure origins have been reported. The described etiology has shown a wide
      variety of structural causes such as mesial temporal sclerosis, tumors,
      posttraumatic, cavernomas and cryptogenic epilepsies. METHODS: We retrospectively
      reviewed the incidence of ictal piloerection in the clinical records of patients
      who underwent video-EEG monitoring (VEEGM) between 2007 and 2013 in a multicenter
      cooperative study. All patients presented refractory epilepsies and were
      evaluated with a protocol that included brain MRI, neuropsychology and VEEGM.
      RESULTS: A total of 766 patients were evaluated in four tertiary centers in
      Spain. Five patients showed piloerection as principal seizure semiology
      (prevalence 0.65%). The mean age at seizure onset was 39.6 years and the average
      epilepsy duration was 5.2 years (range 2-14) before diagnosis. Four patients were
      additionally examined with FDG-PET and/or SPECT-SISCOM. All presented temporal
      lobe epilepsy (TLE), three right-sided and two left-sided. A typical unilateral
      hippocampal sclerosis was described in 3 cases. The etiology detected in all
      cases was limbic encephalitis. Three had LGI1, one anti-Hu, and another Ma2
      antibodies. CONCLUSION: Our series describes a so far not well-recognized
      autoimmune association of pilomotor seizures to limbic encephalitis. This
      etiology should be ruled out through a comprehensive diagnostic work-up even in
      cases of long-lasting TLE with typical hippocampal atrophy on MRI.

PMID- 24890934
TI  - Electrogenerated chemiluminescence of tris(2-phenylpyridine)iridium(III) in
      water, acetonitrile and trifluorethanol.
AB  - The spectroscopic, electrochemical and coreactant electrogenerated
      chemiluminescence (ECL) properties of Ir(ppy)3 (where ppy = 2-phenylpyridine)
      have been obtained in aqueous buffered (KH2PO4), 50 : 50 (v/v) acetonitrile
      aqueous buffered (MeCN-KH2PO4) and 30% trifluoroethanol (TFE) solutions. Tri-n
      propylamine was used as the oxidative-reductive ECL coreactant. The
      photoluminescence (PL) efficiency (phiem) of Ir(ppy)3 in TFE (phiem ~ 0.029) was
      slightly higher than in 50 : 50 MeCN-KH2PO4 (phiem ~ 0.0021) and water (phiem ~
      0.00016) compared to a Ru(bpy)32+ standard solution in water (Phiem ~ 0.042). PL
      and ECL emission spectra were nearly identical in all three solvents, with dual
      emission maxima at 510 and 530 nm. The similarity between the ECL and PL spectra
      indicate that the same excited state is probably formed in both experiments. ECL
      efficiencies (phiecl) in 30% TFE solution (phiecl = 0.0098) were higher than
      aqueous solution (phiecl = 0.00092) system yet lower than a 50% MeCN-KH2PO4
      solution (phiecl = 0.0091).

PMID- 24890935
TI  - On apples, oranges, and ARUBA.

PMID- 24890936
TI  - Non-enhanced magnetic resonance angiography can evaluate restenosis after carotid
      artery stenting with the Carotid Wallstent.
AB  - BACKGROUND: Carotid artery stenting (CAS) requires follow-up imaging to assess in
      stent restenosis (ISR). This study aimed to determine whether non-enhanced
      magnetic resonance angiography (NE-MRA) is useful for evaluating ISR. METHOD:
      Between 2009 and 2013, we performed 118 consecutive CAS procedures using the
      Precise stent (n = 78) and the Carotid Wallstent (n = 40). We reviewed 1.5 T NE
      MRA and examined visualization of the stent lumen and the degree of ISR if
      present. Other imaging modalities were used as references. RESULTS: NE-MRA
      performed just after CAS was not able to visualize the stent lumen in all
      patients because of metal artifacts. In the Carotid Wallstent group, follow-up NE
      MRA was available in 22 patients. The stent lumen was visible more than three
      months after CAS in all patients. Among them, >40 % ISR was observed by other
      modalities in eight lesions. The degree of restenosis measured by NE-MRA (y%) had
      a linear relationship with that measured by conventional angiography (x%) (y =
      0.97x-0.4, r = 0.79, P = 0.021). In one case among 17 without ISR (6 %), NE-MRA
      showed false ISR. In the Precise stent group, NE-MRA did not visualize the stent
      lumen in the follow-up period. CONCLUSIONS: NE-MRA can visualize the stent lumen
      in the Carotid Wallstent more than three months after CAS, but not in the Precise
      stent at follow-up. This delayed visualization might depend on endothelialization
      of the stent lumen. The degree of ISR measured by NE-MRA is comparable to that by
      conventional angiography. NE-MRA can evaluate ISR after CAS with the Carotid
      Wallstent (100 % sensitivity and 94 % specificity).

PMID- 24890933
TI  - Postsynaptic potentiation of corticospinal projecting neurons in the anterior
      cingulate cortex after nerve injury.
AB  - Long-term potentiation (LTP) is the key cellular mechanism for physiological
      learning and pathological chronic pain. In the anterior cingulate cortex (ACC),
      postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1
      contribute to the expression of LTP. Here we report that pyramidal cells in the
      deep layers of the ACC send direct descending projecting terminals to the dorsal
      horn of the spinal cord (lamina I-III). After peripheral nerve injury, these
      projection cells are activated, and postsynaptic excitatory responses of these
      descending projecting neurons were significantly enhanced. Newly recruited AMPARs
      contribute to the potentiated synaptic transmission of cingulate neurons. PKA
      dependent phosphorylation of GluA1 is important, since enhanced synaptic
      transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice.
      Our findings provide strong evidence that peripheral nerve injury induce long
      term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down
      projection system provides rapid and profound modulation of spinal sensory
      transmission, including painful information. Inhibiting cortical top-down
      descending facilitation may serve as a novel target for treating neuropathic
      pain. 

PMID- 24890937
TI  - Dosimetric comparison of absolute and relative dose distributions between tissue
      maximum ratio and convolution algorithms for acoustic neurinoma plans in Gamma
      Knife radiosurgery.
AB  - BACKGROUND: The treatment planning for Gamma Knife (GK) stereotactic radiosurgery
      (SRS) that performs dose calculations based on tissue maximum ratio (TMR)
      algorithm has disadvantages in predicting dose in tissue heterogeneity. The
      latest version of the planning software is equipped with a convolution dose
      algorithm as an optional extra and the new algorithm is able to compensate for
      head inhomogeneity. However, the effect of this improved calculation method
      requires detailed validation in clinical cases. In this study, we compared
      absolute and relative dose distributions of treatment plans for acoustic
      neurinoma between TMR and the convolution calculation. METHODS: Twenty-nine
      clinically used plans created by TMR algorithm were recalculated by convolution
      method. Differences between TMR and convolution were evaluated in terms of
      absolute dose (beam-on time), dosimetric parameters including target coverage,
      selectivity, conformity index, gradient index, radical homogeneity index and the
      dose-volume relationship. RESULTS: The discrepancy in estimated absolute dose to
      the target ranged from 1 to 7 % between TMR and convolution. In addition,
      dosimetric parameters of the two methods achieved statistical significance.
      However, it was difficult to see the change of relative dose distribution by
      visual assessment on a monitor. CONCLUSIONS: Convolution, heterogeneity
      correction calculation, and the algorithm are necessary to reduce the dosimetric
      uncertainty of each case in GK SRS.

PMID- 24890938
TI  - Are women's parenting-specific beliefs associated with depressive symptoms in the
      perinatal period? Development of the rigidity of maternal beliefs scale.
AB  - BACKGROUND: Perinatal depression negatively impacts women, parenting, and
      children's development. However, not much is known about maternal specific
      beliefs that may be associated with perinatal depression. We created a new
      measure that examined the rigidity of perinatal women's beliefs in three major
      domains suggested to be closely related to mood and behavior: anticipated
      maternal self-efficacy, perceptions of child vulnerability, and perceptions of
      societal expectations of mothers (PSEM). METHODS: A 26-item measure (the Rigidity
      of Maternal Beliefs Scale, RMBS) was developed and completed by women at two time
      points, pregnancy (n = 134) and postpartum (n = 113), along with the Edinburgh
      Postnatal Depression Scale. Exploratory factor analysis (EFA) examined the factor
      structure of the RMBS and validity and reliability were also tested. RESULTS: The
      EFA suggested that a four-factor solution was most interpretable, with few items
      cross-loading, and there were common themes that unified the items in each
      factor, resulting in a 24-item final measure. Cronbach's alpha confirmed the
      internal consistency, whereas bivariate correlations revealed the measure had
      good test-retest reliability, discriminant validity, and convergent validity.
      Regression analyses established predictive validity of the RMBS for postpartum
      depressive symptoms. CONCLUSIONS: The RMBS may be useful with clinical
      populations to identify maladaptive or rigid thoughts that could be a focus of
      intervention. This tool may also be used to guide conversation about motherhood
      expectations within any context where pregnant women present (e.g., prenatal
      care, social services), as well as potentially identifying women who are at risk
      for postpartum depression in clinical contexts.

PMID- 24890939
TI  - Institutional capacity for health systems research in East and Central African
      schools of public health: knowledge translation and effective communication.
AB  - BACKGROUND: Local health systems research (HSR) provides policymakers and
      practitioners with contextual, evidence-based solutions to health problems.
      However, producers and users of HSR rarely understand the complexities of the
      context within which each operates, leading to the "know-do" gap. Universities
      are well placed to conduct knowledge translation (KT) integrating research
      production with uptake. The HEALTH Alliance Africa Hub, a consortium of seven
      schools of public health (SPHs) in East and Central Africa, was formed to build
      capacity in HSR. This paper presents information on the capacity of the various
      SPHs to conduct KT activities. METHODS: In 2011, each member of the Africa Hub
      undertook an institutional HSR capacity assessment using a context-adapted and
      modified self-assessment tool. KT capacity was measured by several indicators
      including the presence of a KT strategy, an organizational structure to support
      KT activities, KT skills, and institutional links with stakeholders and media.
      Respondents rated their opinions on the various indicators using a 5-point Likert
      scale. Averages across all respondents for each school were calculated.
      Thereafter, each school held a results validation workshop. RESULTS: A total of
      123 respondents from all seven SPHs participated. Only one school had a clear KT
      strategy; more commonly, research was disseminated at scientific conferences and
      workshops. While most respondents perceived their SPH as having strong
      institutional ties with organizations interested in HSR as well as strong
      institutional leadership, the organizational structures required to support KT
      activities were absent. Furthermore, individual researchers indicated that they
      had little time or skills to conduct KT. Additionally, institutional and
      individual links with policymakers and media were reported as weak. CONCLUSIONS:
      Few SPHs in Africa have a clear KT strategy. Strengthening the weak KT capacity
      of the SPHs requires working with institutional leadership to develop KT
      strategies designed to guide organizational structure and development of networks
      with both the media and policymakers to improve research uptake.

PMID- 24890940
TI  - Six-year clinical outcome of single implant-retained mandibular overdentures--a
      pilot study.
AB  - OBJECTIVES: The aim of this prospective pilot study was to evaluate the
      prosthodontic maintenance as well as the implant outcome of single implant
      retained mandibular overdentures over an observation period of 6 years. METHODS:
      Eleven edentulous patients received one single implant in the midline of the
      mandible. Denture bases were temporarily relined and 2 months later provided with
      a ball attachment for implant retention. Implant related parameters and
      prosthodontic maintenance interventions were assessed 4 weeks after implant
      loading and then once a year. RESULTS: Over a mean observation period of 75.9
      months, no implant was lost. The most frequent prosthetic maintenance
      intervention was activation of the matrix due to loss of retention, followed by
      exchange of the female part. Eight denture bases had to be repaired after a
      fracture in the midline area. CONCLUSIONS: Within the limitations of this
      preliminary clinical study, the concept of a single midline implant to retain a
      mandibular complete denture was a successful treatment option for elderly
      edentulous patients.

PMID- 24890941
TI  - Duration of postoperative delirium is an independent predictor of 6-month
      mortality in older adults after hip fracture.
AB  - OBJECTIVES: To evaluate the association between number of days with delirium and
      6-month mortality in elderly adults after hip fracture surgery. DESIGN:
      Prospective cohort study with 6-month follow-up. SETTING: Orthogeriatric Unit
      (OGU). PARTICIPANTS: Individuals (mean age = 84.3 +/- 6.4) admitted to the OGU
      between October 2011 and April 2013 with hip fracture (N = 199). MEASUREMENTS:
      Postoperative delirium (POD) was assessed daily using the Confusion Assessment
      Method algorithm and the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, Text Revision, criteria. Multivariable Cox regression models were
      used to evaluate the association between POD of and 6-month mortality after
      surgery, after adjustment for covariates including age, prefracture residence,
      Katz activity of daily living score, New Mobility score, diagnosis of prefracture
      dementia, American Society of Anesthesiologists score, albumin serum levels,
      Charlson Comorbidity Index, and length of OGU stay. RESULTS: Fifty-seven
      participants (28.6%) developed POD. In the 6-month period after surgery, 35
      (17.6%) participants died: 16 of 57 (28.1%) with POD and 19/ of 142 (13.4%) with
      no POD. The average duration of POD was 2.0 +/- 3.2 days for participants who
      died and 0.7 +/- 1.8 days for those who survived (P < .001). After adjusting for
      covariates, each day of POD in the OGU increased the hazard of dying at 6 months
      by 17% (hazard ratio = 1.17, 95% confidence interval = 1.07-1.28). CONCLUSION: In
      older adults undergoing hip fracture surgery, duration of POD is an important
      prognostic factor for 6-month mortality. Efforts to reduce duration of POD are
      therefore crucial for these individuals.

PMID- 24890942
TI  - Binding domain-driven intracellular trafficking of sterols for synthesis of
      steroid hormones, bile acids and oxysterols.
AB  - Steroid hormones, bioactive oxysterols and bile acids are all derived from the
      biological metabolism of lipid cholesterol. The enzymatic pathways generating
      these compounds have been an area of intense research for almost a century, as
      cholesterol and its metabolites have substantial impacts on human health. Owing
      to its high degree of hydrophobicity and the chemical properties that it confers
      to biological membranes, the distribution of cholesterol in cells is tightly
      controlled, with subcellular organelles exhibiting highly divergent levels of
      cholesterol. The manners in which cells maintain such sterol distributions are of
      great interest in the study of steroid and bile acid synthesis, as limiting
      cholesterol substrate to the enzymatic pathways is the principal mechanism by
      which production of steroids and bile acids is regulated. The mechanisms by which
      cholesterol moves within cells, however, remain poorly understood. In this
      review, we examine the subcellular machinery involved in cholesterol metabolism
      to steroid hormones and bile acid, relating it to both lipid- and protein-based
      mechanisms facilitating intracellular and intraorganellar cholesterol movement
      and delivery to these pathways. In particular, we examine evidence for the
      involvement of specific protein domains involved in cholesterol binding, which
      impact cholesterol movement and metabolism in steroidogenesis and bile acid
      synthesis. A better understanding of the physical mechanisms by which these
      protein- and lipid-based systems function is of fundamental importance to
      understanding physiological homeostasis and its perturbation. 

PMID- 24890945
TI  - Isolated IgG4-related sclerosing cholangitis: a report of 9 cases.
AB  - Extrahepatic bile ducts are the most commonly involved extrapancreatic organ site
      in patients with type 1 autoimmune pancreatitis. IgG4-related sclerosing
      cholangitis (IgG4-SC) alone, without evidence of pancreatic or other organ
      involvement, is uncommon and is difficult to distinguish from cholangiocarcinoma
      preoperatively. We describe 9 patients with isolated IgG4-SC over an approximate
      10-year period, each clinically suspected to have cholangiocarcinoma. We examined
      the clinical, radiological, cytologic (including fluorescence in situ
      hybridization results), and histologic features. IgG and IgG4
      immunohistochemistry were performed. All 9 patients were middle-aged men who
      presented with obstructive jaundice. The biliary strictures involved all parts of
      the extrahepatic biliary tree. Serum IgG4 was slightly elevated in three of eight
      patients. Cytologic findings were interpreted as negative in six, atypical in
      one, and suspicious for adenocarcinoma in one. Fluorescence in situ hybridization
      revealed aneuploidy in one and was equivocal (trisomy 7) in 2. Eight of 9
      patients underwent radical resection for suspected cholangiocarcinoma. There was
      only one case diagnosed with IgG4-SC preoperatively based on biopsy. Histologic
      sections revealed a prominent lymphoplasmacytic infiltrate with storiform
      fibrosis and marked increased IgG4-positive plasma cells (>=30/high-power field)
      in all specimens. Fifty percent of cases (4/8) had IgG4/IgG plasma cell ratio
      >40%. On median follow-up of 2.8 years, no relapse has occurred in any patient.
      Extrahepatic IgG4-SC may present as an isolated lesion mimicking
      cholangiocarcinoma. The diagnosis can be challenging. Clinicians and pathologists
      should recognize this to avoid major surgery. 

PMID- 24890943
TI  - MicroRNA expression patterns in adrenocortical carcinoma variants and clinical
      pathologic correlations.
AB  - Several microRNAs (miRNAs) were shown to be deregulated in adrenocortical
      carcinoma (ACC) as compared with adenoma, but a detailed assessment of their
      expression in its histologic variants and correlation with clinicopathologic
      characteristics has not been performed, so far. Our aim was to assess the
      expression of 5 selected miRNAs (IGF2 gene-related miR-483-3p and 5p and hypoxia
      induced miR-210, miR-195, and miR-1974) in a series of 51 ACCs (35 classical, 6
      myxoid, and 10 oncocytic) as compared with clinical and pathologic features and
      immunohistochemical expression of prognostic markers, including steroidogenic
      factor 1, p53, beta-catenin, and glucose transporter 1. Oncocytic carcinomas had
      a reduced expression of miR-483-3p (P = .0325), miR-483-5p (P = .0175), and miR
      210 (P = .0366), as compared with other histotypes. Overexpression of miR-210 was
      associated with the presence of necrosis (P = .0035), high Ki-67 index (P =
      .0013), and high glucose transporter 1 expression (P = .0043), whereas an inverse
      correlation with mitotic rate was observed in cases with high miR-493-3p (P =
      .0191) and miR-1974 (P = .0017) expression. High miR-1974 was also associated
      with low Ki-67 (P = .0312) and European Network for the Study of Adrenal Tumors
      stage (P = .0082) and negative p53 (P = .0013). At univariate analysis
      myxoid/classic histotype (P = .026), high miR-210 (P = .0465), high steroidogenic
      factor 1 protein (P = .0017), high Ki-67 (P = .0066), and high mitotic index (P =
      .0006) were significantly associated the shorter overall survival, the latter
      being the sole independent prognostic factor at multivariate analysis (P = .017).
      In conclusion, (a) miR-483-3p, miR-483-5p, and miR-210 are differentially
      expressed in ACC variants, and (b) high miR-210 is associated with
      clinicopathologic parameters of aggressiveness and a poor prognosis. 

PMID- 24890944
TI  - Enhanced immunohistochemical detection of neural infiltration in primary
      melanoma: is there a clinical value?
AB  - Neural infiltration in primary melanoma is a histopathologic feature that has
      been associated with desmoplastic histopathologic subtype and local recurrence in
      the literature. We tested the hypothesis that improved detection and
      characterization of neural infiltration into peritumoral or intratumoral location
      and perineural or intraneural involvement could have a prognostic relevance. We
      studied 128 primary melanoma cases prospectively accrued and followed at New York
      University using immunohistochemical detection with antihuman neurofilament
      protein and routine histology with hematoxylin and eosin. Neural infiltration,
      defined as the presence of tumor cells involving or immediately surrounding nerve
      foci, was identified and characterized using both detection methods. Neural
      infiltration rate of detection was enhanced by immunohistochemistry for
      neurofilament in matched-pair design (47% by immunohistochemistry versus 25% by
      routine histology). Immunohistochemical detection of neural infiltration was
      significantly associated with ulceration (P = .021), desmoplastic and acral
      lentiginous histologic subtype (P = .008), and head/neck/hands/feet tumor
      location (P = .037). Routinely detected neural infiltration was significantly
      associated with local recurrence (P = .010). Immunohistochemistry detected more
      intratumoral neural infiltration cases compared with routine histology (30%
      versus 3%, respectively). Peritumoral and intratumoral nerve location had no
      impact on clinical outcomes. Using a multivariate model controlling for stage,
      neither routinely detected neural infiltration nor enhanced immunohistochemical
      characterization of neural infiltration was significantly associated with disease
      free or overall survival. Our data demonstrate that routinely detected neural
      infiltration is associated with local recurrence in all histologic subtypes but
      that improved detection and characterization of neural infiltration with
      immunohistochemistry in primary melanoma does not add to prognostic relevance. 

PMID- 24890946
TI  - The first report of adolescent TAFRO syndrome, a unique clinicopathologic variant
      of multicentric Castleman's disease.
AB  - BACKGROUND: TAFRO syndrome is a unique clinicopathologic variant of multicentric
      Castleman's disease that has recently been identified in Japan. It is
      characterized by a constellation of symptoms: Thrombocytopenia, Anasarca,
      reticulin Fibrosis of the bone marrow, Renal dysfunction and Organomegaly
      (TAFRO). Previous reports have shown that affected patients usually respond to
      immunosuppressive therapy, but the disease sometimes has a fatal course. TAFRO
      syndrome occurs in the middle-aged and elderly and there are no prior reports of
      the disease in adolescents. Here we report the first adolescent case,
      successfully treated with anti-IL-6 receptor antibody (tocilizumab, TCZ) and
      monitored with serial cytokine profiles. CASE PRESENTATION: A 15-year-old
      Japanese boy was referred to us with fever of unknown origin. Whole body computed
      tomography demonstrated systemic lymphadenopathy, organomegaly and anasarca.
      Laboratory tests showed elevated C-reactive protein and hypoproteinemia. Bone
      marrow biopsy revealed a hyperplastic marrow with megakaryocytic hyperplasia and
      mild reticulin fibrosis. Despite methylprednisolone pulse therapy, the disease
      progressed markedly to respiratory distress, acute renal failure, anemia and
      thrombocytopenia. Serum and plasma levels of cytokines, including IL-6, vascular
      endothelial growth factor, neopterin and soluble tumor necrosis factor receptors
      I and II, were markedly elevated. Repeated weekly TCZ administration dramatically
      improved the patient's symptoms and laboratory tests showed decreasing cytokine
      levels. CONCLUSION: To our knowledge, this is the first report of TAFRO syndrome
      in a young patient, suggesting that this disease can occur even in adolescence.
      The patient was successfully treated with TCZ. During our patient's clinical
      course, monitoring cytokine profiles was useful to assess the disease activity of
      TAFRO syndrome.

PMID- 24890948
TI  - Experiences and the use of BNP POCT platform on suspected ischemic stroke
      patients in the emergency department setting.

PMID- 24890947
TI  - Hydrogen gas protects against serum and glucose deprivation-induced myocardial
      injury in H9c2 cells through activation of the NF-E2-related factor 2/heme
      oxygenase 1 signaling pathway.
AB  - Ischemia or hypoxia-induced myocardial injury is closely associated with
      oxidative stress. Scavenging free radicals and/or enhancing endogenous
      antioxidative defense systems may be beneficial for the impediment of myocardial
      ischemic injury. Hydrogen (H2) gas, as a water- and lipid-soluble small molecule,
      is not only able to selectively eliminate hydroxyl (.OH) free radicals, but also
      to enhance endogenous antioxidative defense systems in rat lungs and arabidopsis
      plants. However, thus far, it has remained elusive whether H2 gas protects
      cardiomyocytes through enhancement of endogenous antioxidative defense systems.
      In the present study, the cardioprotective effect of H2 gas against ischemic or
      hypoxic injury was investigated, along with the underlying molecular mechanisms.
      H9c2 cardiomyoblasts (H9c2 cells) were treated in vitro with a chemical hypoxia
      inducer, cobalt chloride (CoCl2), to imitate hypoxia, or by serum and glucose
      deprivation (SGD) to imitate ischemia. Cell viability and intracellular .OH free
      radicals were assessed. The role of an endogenous antioxidative defense system,
      the NF-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway, was
      evaluated. The findings revealed that treatment with CoCl2 or SGD markedly
      reduced cell viability in H9c2 cells. H2 gas-rich medium protected against cell
      injury induced by SGD, but not that induced by CoCl2. When the cells were exposed
      to SGD, levels of intracellular .OH free radicals were markedly increased; this
      was mitigated by H2 gas-rich medium. Exposure of the cells to SGD also resulted
      in significant increases in HO-1 expression and nuclear Nrf2 levels, and the HO-1
      inhibitor ZnPP IX and the Nrf2 inhibitor brusatol aggravated SGD-induced cellular
      injury. H2 gas-rich medium enhanced SGD-induced upregulation of HO-1 and Nrf2,
      and the HO-1 or Nrf2 inhibition partially suppressed H2 gas-induced
      cardioprotection. Furthermore, following genetic silencing of Nrf2 by RNA
      interference, the effects of H2 gas on the induction of HO-1 and cardioprotection
      were markedly reduced. In conclusion, H2 gas protected cardiomyocytes from
      ischemia-induced myocardial injury through elimination of .OH free radicals and
      also through activation of the Nrf2/HO-1 signaling pathway. 

PMID- 24890949
TI  - Cyanide-bridged decanuclear cobalt-iron cage.
AB  - A cyanide-bridged decanuclear [Co6Fe4] cluster was synthesized by a one-pot
      reaction, and the magnetic properties and electronic configuration were
      investigated. The complex displayed thermally controlled electron-transfer
      coupled spin transition (ETCST) behavior between Co(III) low-spin-NC-Fe(II) low
      spin and Co(II) high-spin-NC-Fe(III) low-spin states, as confirmed by single
      crystal X-ray, magnetic, and Mossbauer analyses. 

PMID- 24890950
TI  - In reference to "patient-centered blood management".

PMID- 24890951
TI  - A synthetic biotinylated peptide, BP21, inhibits the induction of mRNA expression
      of inflammatory substances by oxidized- and lyso-phosphatidylcholine.
AB  - Preclinical Research Oxidized low-density lipoprotein (ox-LDL) is implicated in
      many inflammatory diseases, e.g., type 2 diabetes, obesity, atherosclerosis, and
      metabolic syndrome. We previously reported that a synthetic biotinylated peptide,
      BP21, inhibits the bioactivity of ox-LDL via direct binding to ox-LDL. Here, we
      investigated the effect of BP21 on the mRNA expression of proinflammatory
      mediators induced by two major components of ox-LDL, oxidized- and lyso
      phosphatidylcholine (ox-PC and LPC), in monocytes/macrophages (THP-1 cells) and
      adipocytes (3T3-L1 cells). In THP-1 cells, BP21 markedly reduced the mRNA
      expression of interleukin (IL)-6, adipocyte fatty acid-binding protein (aP2),
      tumor necrosis factor-alpha, and mitogen-activated protein kinase phosphatase-1,
      which are induced by one of the major bioactive components of ox-PC, 1-palmitoyl
      2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), and reduced the mRNA
      expression of IL-6, the ox-LDL-specific scavenger receptor CD36, and aP2 induced
      by LPC. In adipocytes, the mRNA expression of IL-1beta as an adipokine and aP2 is
      highly induced by ox-PC and LPC, and BP21 markedly reduced the mRNA expression of
      IL-1beta and aP2 induced by POVPC and LPC. Furthermore, BP21 specifically bound
      to LPC and POVPC in a dose-dependent manner. These results suggest that BP21 may
      be useful lead for the potential treatment and prevention of inflammatory
      diseases caused by ox-PC and LPC. 

PMID- 24890952
TI  - Helicobacter pylori antimicrobial resistance rates in the central region of
      Portugal.
AB  - Helicobacter pylori resistance to antimicrobial agents is steadily increasing. It
      is extremely important to be aware of the local prevalence of antibiotic
      resistance so as to adjust treatment strategies. During this single-centre,
      prospective study, we aimed to determine primary and secondary resistance rates
      of H. pylori to antibiotics as well as host and bacterial factors associated with
      this problem. Overall, 180 patients (131 female; mean age 43.4+/-13.5 years;
      primary resistance 103; secondary resistance 77) with positive (13) C-urea breath
      test were submitted to upper endoscopy with gastric biopsies. Helicobacter pylori
      was cultured and antimicrobial susceptibility was determined by Etest and
      molecular methods. Clinical and microbiological characteristics associated with
      resistance were evaluated by logistic regression analysis. Among the 180 isolates
      50% were resistant to clarithromycin (primary 21.4%; secondary 88.3%), 34.4% to
      metronidazole (primary 29.1%; secondary 41.6%), 33.9% to levofloxacin (primary
      26.2%; secondary 44.2%), 0.6% to tetracycline and 0.6% to amoxicillin. Being
      female was an independent predictor of resistance to clarithromycin and
      metronidazole. Previous, failed, eradication treatments were also associated with
      a decrease in susceptibility to clarithromycin. History of frequent infections,
      first-degree relatives with gastric carcinoma and low education levels determined
      increased resistance to levofloxacin. Mutations in the 23S rRNA and gyrA genes
      were frequently found in isolates with resistance to clarithromycin and
      levofloxacin, respectively. This study revealed that resistance rates to
      clarithromycin, metronidazole and levofloxacin are very high and may compromise
      H. pylori eradication with first-line and second-line empiric triple treatments
      in Portugal.

PMID- 24890954
TI  - Antimicrobial resistance.

PMID- 24890953
TI  - Kinematics and subpopulations' structure definition of blue fox (Alopex lagopus)
      sperm motility using the ISAS(r) V1 CASA system.
AB  - Over recent years, technological advances have brought innovation in assisted
      reproduction to the agriculture. Fox species are of great economical interest in
      some countries, but their semen characteristics have not been studied enough. To
      advance the knowledge of function of fox spermatozoa, five samples were obtained
      by masturbation, in the breeding season. Kinetic analysis was performed using
      ISAS(r) v1 system. Usual kinematic parameters (VCL, VSL, VAP, LIN, STR, WOB, ALH
      and BCF) were considered. To establish the standardization for the analysis of
      samples, the minimum number of cells to analyse and the minimum number of fields
      to capture were defined. In the second step, the presence of subpopulations in
      blue fox semen was analysed. The minimum number of cells to test was 30, because
      kinematic parameters remained constant along the groups of analysis. Also, the
      effectiveness of ISAS(r) D4C20 counting chamber was studied, showing that the
      first five squares presented equivalent results, while in the squares six and
      seven, the kinematic parameters showed a reduction in all of them, but not in the
      concentration or motility percentage. Kinematic variables were grouped into two
      principal components (PC). A linear movement characterized PC1, while PC2 showed
      an oscillatory movement. Three subpopulations were found, varying in structure
      among different animals.

PMID- 24890955
TI  - Australian Group on Antimicrobial Resistance Enterococcus Surveillance Programme
      annual report, 2010.
AB  - In 2010, 15 institutions around Australia conducted a period prevalence study of
      key resistances in isolates of Enterococcus species associated with a range of
      clinical disease amongst in- and outpatients. Each institution collected up to
      100 consecutive isolates and tested these for susceptibility to commonly used
      antimicrobials using standardised methods. Vancomycin-resistant Enterococcus
      faecium and Enterococcus faecalis were characterised by pulsed-field gel
      electrophoresis. Multilocus sequence typing was performed on representative
      pulsotypes of E. faecium. Susceptibility results were compared with similar
      surveys conducted in 1995, 1999, 2003, 2005, 2007 and 2009. In the 2010 survey,
      E. faecalis (1,201 isolates) and E. faecium (170 isolates) made up 98.9% of the
      1,386 isolates tested. Ampicillin resistance was very common (85.3%) in E.
      faecium and absent in E. faecalis. Non-susceptibility to vancomycin was 36.5% in
      E. faecium (similar to the 35.2% in 2009 but up from 15.4% in the 2007 survey)
      and 0.5% in E. faecalis. There were significant differences in the proportion of
      vancomycin-resistant E. faecium between the states ranging from 0% in Western
      Australia to 54.4% in South Australia. The vanB gene was detected in 62 E.
      faecium and 3 E. faecalis isolates. The vanA gene was detected in 1 E. faecium
      isolate. All vancomycin-resistant E. faecium belonged to clonal complex 17. The
      most common sequence type (ST) was ST203, which was found in all regions that had
      reports of vancomycin resistant enterococci. ST341 was detected only in New South
      Wales/Australian Capital Territory and ST414 only in South Australia and
      Victoria. High-level resistance to gentamicin was 34.1% in E. faecalis and 66.1%
      in E. faecium. A subset of isolates was tested against high-level streptomycin,
      linezolid and quinupristin/dalfopristin. High-level streptomycin resistance was
      found in 8.2% of E. faecalis isolates and 43.8% of E. faecium isolates. Linezolid
      non-susceptibility was more common in E. faecalis (5.8%) than E. faecium (0.9%).
      Overall 9.4% of E. faecium were resistant to quinupristin/dalfopristin (E.
      faecalis is intrinsically resistant). 

PMID- 24890956
TI  - Australian Group on Antimicrobial Resistance Hospital-onset Staphylococcus aureus
      Surveillance Programme annual report, 2011.
AB  - In 2011, the Australian Group on Antimicrobial Resistance (AGAR) conducted a
      period-prevalence survey of clinical Staphylococcus aureus isolated from hospital
      inpatients. Twenty-nine microbiology laboratories from all states and mainland
      territories participated. Specimens were collected more than 48 hours post
      admission. Isolates were tested by Vitek2(r) antimicrobial susceptibility card
      (AST-P612 card). Nationally, the proportion of S. aureus that were methicillin
      resistant S. aureus (MRSA) was 30.3%; ranging from 19.9% in Western Australia to
      36.8% in New South Wales/Australian Capital Territory. Resistance to the non-beta
      lactam antimicrobials was common except for rifampicin, fusidic acid, high-level
      mupirocin and daptomycin. No resistance was detected for vancomycin, teicoplanin
      or linezolid. Antibiotic resistance in methicillin susceptible S. aureus (MSSA)
      was rare apart from erythromycin (13.2%) and there was no resistance to
      vancomycin, teicoplanin or linezolid. Inducible clindamycin resistance was the
      norm for erythromycin resistant, clindamycin intermediate/susceptible S. aureus
      in Australia with 90.6% of MRSA and 83.1% of MSSA with this phenotype having a
      positive double disc diffusion test (D-test). The proportion of S. aureus
      characterised as being healthcare-associated MRSA (HA-MRSA) was 18.2%, ranging
      from 4.5% in Western Australia to 28.0% in New South Wales/Australian Capital
      Territory. Four HA-MRSA clones were characterised and 98.8% of HA-MRSA isolates
      were classified as either ST22-IV [2B] (EMRSA-15) or ST239-III [3A] (Aus-2/3
      EMRSA). Multiclonal community-associated MRSA (CA-MRSA) accounted for 11.7% of
      all S. aureus. In Australia, regional variation in resistance is due to the
      differential distribution of MRSA clones between regions, particularly for the
      major HA-MRSA clone, ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to
      multiple non-beta-lactam antimicrobials. 

PMID- 24890958
TI  - Australian Meningococcal Surveillance Programme annual report, 2012.
AB  - In 2012, there were 208 laboratory-confirmed cases of invasive meningococcal
      disease (IMD) analysed by the National Neisseria Network, and 222 cases notified
      to the National Notifiable Diseases Surveillance System, thus laboratory data
      were available for 93.7% of cases of IMD in Australia in 2012. Isolates of
      Neisseria meningitidis from 116 invasive cases of meningococcal disease were
      available for testing, and the phenotype (serogroup, serotype and serosubtype)
      and/or genotype, and antibiotic susceptibility were determined. Molecular typing
      was performed for the 92 cases confirmed by nucleic acid amplification testing
      (NAAT). Typing information was available for 194 of the 208 laboratory confirmed
      cases and 83% (161 cases) were serogroup B infections, 5.7% (11 cases) were
      serogroup C infections, 3.6% (11 cases) were serogroup W135, and 7.7% (15 cases)
      were serogroup Y meningococci. The number of laboratory confirmed IMD cases in
      2012 was the lowest since laboratory surveillance data have been reported.
      Primary and secondary disease peaks were observed in those aged 4 years or less
      and in adolescents (15-19 years) and young adults (20-24 years), respectively.
      Serogroup B cases predominated in all age groups and jurisdictions. In 2012, the
      most common porA genotype circulating in Australia was P1.7-2,4. Serogroup C,
      W135 and Y cases were numerically low, similar to previous years. Decreased
      susceptibility to the penicillin group of antibiotics was observed in 81.9% of
      isolates, and 1 isolate exhibited resistance to penicillin. All isolates remained
      susceptible to ceftriaxone, ciprofloxacin and rifampicin. 

PMID- 24890957
TI  - Australian Group on Antimicrobial Resistance Community-onset Gram-negative
      Surveillance Program annual report, 2010.
AB  - The Australian Group on Antimicrobial Resistance (AGAR) performs regular period
      prevalence studies to monitor changes in antimicrobial resistance in selected
      enteric Gram-negative pathogens. The 2010 survey focussed on community-onset
      infections, examining isolates from urinary tract infections from patients
      presenting to outpatient clinics, emergency departments or to community
      practitioners. Two thousand and ninety-two Escherichia coli, 578 Klebsiella
      species and 268 Enterobacter species were tested using a commercial automated
      method (Vitek 2, BioMerieux) and results were analysed using Clinical and
      Laboratory Standards Institute breakpoints from January 2012. Of the key
      resistances, non-susceptibility to the third-generation cephalosporin,
      ceftriaxone, was found in 3.2% of E. coli and 3.2%-4.0% of Klebsiella spp. Non
      susceptibility rates to ciprofloxacin were 5.4% for E. coli, 1.0%-2.3% for
      Klebsiella spp., and 2.5%-6.6% in Enterobacter spp, and resistance rates to
      piperacillin-tazobactam were 2.8%, 3.2%-6.9%, and 16.8%-18.0% for the same 3
      groups respectively. Only 3 strains, 2 Klebsiella spp. and 1 Enterobacter spp,
      were shown to harbour a carbapenemase (IMP-4). 

PMID- 24890959
TI  - Australian Gonococcal Surveillance Programme annual report, 2012.
AB  - The Australian Gonococcal Surveillance Programme has continuously monitored
      antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae from all
      states and territories since 1981. In 2012, 4,718 clinical isolates of gonococci
      from public and private sector sources were tested for in vitro antimicrobial
      susceptibility by standardised methods. Variation in antibiotic susceptibility
      patterns were reported between jurisdictions and regions. Resistance to the
      penicillins and quinolones was high in all jurisdictions except the Northern
      Territory and Tasmania. Penicillin resistance ranged from 21% in Western
      Australia to 53% in Victoria. Quinolone resistance ranged from 17% in Queensland
      to 46% in Victoria, and the resistance was mostly high level. Decreased
      susceptibility to ceftriaxone (MIC 0.06-0.25 mg/L or greater) was found
      nationally in 4.4% of isolates, an increase from 3.2% in 2011, but lower than in
      2010. To date, there has not been an isolate of N. gonorrhoeae with a ceftriaxone
      MIC value greater than 0.125 mg/L reported in Australia. Azithromycin
      susceptibility testing was performed in all jurisdictions and resistance ranged
      from 0.3% in the Northern Territory to 2.7% in Victoria. The highest reported
      azithromycin MIC value was 16 mg/L and azithromycin resistant gonococci were not
      detected in the Australian Capital Territory or Tasmania. Nationally, all
      isolates remained susceptible to spectinomycin. 

PMID- 24890960
TI  - Impacts of a measles outbreak in Western Sydney on public health resources.
AB  - During February and March 2011, an outbreak of 26 confirmed cases of measles was
      reported to the Parramatta Public Health Unit (PHU) in western Sydney. This paper
      describes the impact of the outbreak on PHU resources. A retrospective review of
      information obtained from case notification forms and associated contact tracing
      records was carried out for each of the confirmed cases. Seven cases (27%)
      required hospital admission for more than 1 day and 10 (38%) cases required
      management within a hospital emergency department. There were no cases of
      encephalitis or death. The number of contacts was determined for each case as
      well as the number who required post-exposure prophylaxis. In total, 1,395
      contacts were identified in this outbreak. Of these, 79 (5.7%) required normal
      human immunoglobulin and 90 (6.5%) were recommended to receive the measles-mumps
      rubella vaccine. A case study detailing the PHU costs associated with the contact
      management of a hospitalised measles case with 75 identified contacts is also
      included and the estimated total cost to the PHU of containing this particular
      case of measles was A$2,433, with staff time comprising the major cost component.
      Considerable effort and resources are required to manage measles outbreaks. The
      total cost of this outbreak to the PHU alone is likely to have exceeded A$48,000.

PMID- 24890961
TI  - Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel
      Australian hospitals in 2012: the Influenza Complications Alert Network (FluCAN).
AB  - Influenza is mostly a mild, self-limiting infection and severe infection
      requiring hospitalisation is uncommon. Immunisation aims to reduce serious
      morbidity and mortality. The Influenza Complications Alert Network (FluCAN) is a
      sentinel hospital-based surveillance program that operates at 15 sites across all
      states and territories in Australia. This study reports on the epidemiology of
      hospitalisation with confirmed influenza, estimate vaccine coverage and influenza
      vaccine protection against hospitalisation with influenza during the 2012
      influenza season. In this observational study, cases were defined as patients
      admitted to one of the sentinel hospitals with influenza confirmed by nucleic
      acid detection. Controls were patients who had acute respiratory illnesses who
      were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus
      the odds ratio of vaccination in case patients compared with control patients,
      after adjusting for known confounders. During the period 9 April to 31 October
      2012, 1,231 patients were admitted with confirmed influenza at the 15 FluCAN
      sentinel hospitals. Of these, 47% were more than 65 years of age, 8% were
      Indigenous Australians, 3% were pregnant and 76% had chronic co-morbidities.
      Influenza A was detected in 83% of patients. Vaccination coverage was calculated
      from the vaccination status of 1,216 test negative controls and was estimated at
      77% in patients 65 years or over and 61% in patients with chronic comorbidities.
      Vaccination effectiveness was estimated at 41% (95% CI: 28%, 51%, P<0.001).
      Vaccine coverage was incomplete in at-risk groups, particularly non-elderly
      patients with medical comorbidities. The study results suggest that the seasonal
      influenza vaccine was moderately protective against hospitalisation with
      influenza during the 2012 season. 

PMID- 24890962
TI  - Enhanced surveillance for gonorrhoea in two diverse settings in Queensland in the
      2000s: comparative epidemiology and selected management outcomes.
AB  - Gonorrhoea is an important sexually transmitted notifiable condition. This paper
      describes findings from two gonorrhoea enhanced surveillance programs operating
      during the 2000s in Queensland: one in the remote Torres and Northern Peninsula
      Area (T&NPA); the other in an urban region. The overall response rate in the
      T&NPA (2006-2011) was 82% (723 of 879), and in Brisbane Southside and West
      Moreton (BSWM) (2003-2011), it was 62% (1,494 of 2,401 notifications). In the
      T&NPA, cases were young (80% <25 years), Indigenous (97%) and 44% were male. In
      the BSWM, cases were predominantly male (76%), non-Indigenous (92%) and 42% were
      aged less than 25 years. Co-infection with chlamydia was found in 54% of males
      and 60% of females in the Torres, and in 18% of males and 35% of females in the
      BSWM. In the BSWM 35% of the men without a syphilis test recorded had reported
      sexual contact with men; similarly 34% of the men without an HIV test recorded
      had reported sexual contact with men. Compliance with recommended treatment
      (ceftriaxone) was greater than 90% in all years except 2008 (84%) in the T&NPA.
      Treatment compliance increased significantly, from 40% in 2003 to 84.4% in 2011
      (P<0.0001) in the BSWM cohort. The proportion of contacts with a documented
      treatment date increased significantly in the T&NPA from 56% in 2009 to 76% in
      2011 (P=0.019), after a system for follow-up with the clinician became routine.
      Gonorrhoea epidemiology and management challenges vary across Queensland
      populations. Enhanced surveillance allows public health authorities to monitor
      epidemiology and reminds clinicians to prioritise effective sexually transmitted
      infection treatment for their clients. 

PMID- 24890963
TI  - OzFoodNet quarterly report, 1 July to 30 September 2012.

PMID- 24890964
TI  - National Notifiable Diseases Surveillance System, 1 April to 30 June 2013.

PMID- 24890965
TI  - Australian childhood immunisation coverage, 1 April to 30 June cohort, assessed
      as at 30 September 2012.

PMID- 24890966
TI  - Australian childhood immunisation coverage, 1 October to 31 December cohort,
      assessed as at 31 March 2013.

PMID- 24890967
TI  - Australian Gonococcal Surveillance Programme, 1 January to 31 March 2013.

PMID- 24890968
TI  - Australian Gonococcal Surveillance Programme, 1 April to 30 June 2013.

PMID- 24890969
TI  - Australian Meningococcal Surveillance Programme quarterly report, 1 April to 30
      June 2013.

PMID- 24890970
TI  - Australian Sentinel Practices Research Network, 1 July to 30 September 2012.

PMID- 24890971
TI  - Invasive pneumococcal disease surveillance Australia, 1 April to 30 June 2013.

PMID- 24890972
TI  - Iron near absorption edge X-ray spectroscopy at aqueous-membrane interfaces.
AB  - Employing synchrotron X-ray scattering, we systematically determine the
      absorption near-edge spectra (XANES) of iron in its ferrous (Fe(2+)) and ferric
      (Fe(3+)) states both as ions in aqueous solutions and as they bind to form a
      single layer to anionic templates that consist of carboxyl or phosphate groups at
      aqueous/vapor interfaces. While the XANES of bulk iron ions show that the
      electronic state and coordination of iron complexes in the bulk are isotropic,
      the interfacial bound ions show a signature of a broken inversion-symmetry
      environment. The XANES of Fe(2+) and Fe(3+) in the bulk possess distinct profiles
      however, upon binding they practically exhibit similar patterns. This indicates
      that both bound ions settle into a stable electronic and coordination
      configuration with an effective fractional valence (for example, Fe([2+nu]+), 0 <
      nu < 1) at charged organic templates. Such two dimensional properties may render
      interfacial iron, abundant in living organisms, a more efficient and versatile
      catalytic behavior. 

PMID- 24890973
TI  - TOUCH of the healer: Defining core behaviors of oncologists that affect the
      mental health of patients with cancer.

PMID- 24890974
TI  - Modulation of mesenchymal stromal cell characteristics by microcarrier culture in
      bioreactors.
AB  - Mesenchymal stromal cells (MSCs) are promising candidates for cell therapy. Their
      therapeutic use requires extensive expansion to obtain a sufficiently high number
      of cells for clinical applications. State-of-the-art expansion systems, that is,
      primarily culture flask-based systems, are limited regarding scale-up,
      automation, and reproducibility. To overcome this bottleneck, microcarrier (MC)
      based expansion processes have been developed. For the first time, MSCs from the
      perinatal sources umbilical cord (UC) and amniotic membrane (AM) were expanded on
      MCs. This study focuses on the comparison of flask- and Cytodex 1 MC-expanded
      MSCs by evaluating the influence of the expansion process on biological MSC
      characteristics. Furthermore, we tested the hypothesis to obtain more homogeneous
      MSC preparations by expanding cells on MCs in controlled large-scale bioreactors.
      MSCs were extensively characterized determining morphology, cell growth, surface
      marker expression, and functional properties such as differentiation capacity,
      secretion of paracrine factors, and gene expression. Based on their gene
      expression profile MSCs from different donors and sources clearly clustered in
      distinct groups solely depending on the expansion process-MC or flask culture. MC
      and flask-expanded MSCs significantly differed from each other regarding surface
      markers and both paracrine factors and gene expression profiles. Furthermore,
      based on gene expression analysis, MC cultivation of MSCs in controlled
      bioreactor systems resulted in less heterogeneity between cells from different
      donors. In conclusion, MC-based MSC expansion in controlled bioreactors has the
      potential to reliably produce MSCs with altered characteristics and functions as
      compared to flask-expanded MSCs. These findings may be useful for the generation
      of MSCs with tailored properties for clinical applications.

PMID- 24890975
TI  - Evolution of alternative male morphotypes in oxyurid nematodes: a case of
      convergence?
AB  - Male dimorphism has been reported across different taxa and is usually expressed
      as the coexistence of a larger morph with exaggerated male traits and a smaller
      one with reduced traits. The evolution and maintenance of male dimorphism are
      still poorly understood for several of the species in which it has been observed.
      Here, we analyse male dimorphism in several species of reptile parasitic
      nematodes of the genus Spauligodon, in which a major male morph (exaggerated
      morph), which presents the traditional male morphological traits reported for
      this taxon, coexists with a minor morph with reduced morphological traits (i.e.
      reduced genital papillae) resembling more closely the males of the sister genus
      Skrjabinodon than Spauligodon major males. Because of the level of uncertainty in
      the results of ancestral state reconstruction, it is unclear if the existence of
      male dimorphism in this group represents independent instances of convergent
      evolution or an ancestral trait lost multiple times. Also, although the number of
      major males per host was positively correlated with the number of females, the
      same did not hold true for minor males, whose presence was not associated with
      any other ecological factor. Nevertheless, the existence of male dimorphism in
      Spauligodon nematodes is tentatively interpreted as resulting from alternative
      reproductive tactics, with differences in presence and number of individuals as
      indicators of differences in fitness, with the lower numbers of minor males per
      host likely maintained by negative frequency-dependent selection. 

PMID- 24890976
TI  - The effect of nasal structure on olfactory function in patients with OSA.
AB  - The aim of this study was to investigate the relationship between nasal structure
      and olfactory function in patients with obstructive sleep apnea (OSA). Olfaction
      and nasal structure of 76 adults with OSA diagnosed by polysomnography were
      measured using acoustic rhinometry and the Sniffin, Sticks (SS) smell test at
      Anzhen Hospital, a major academic center in Beijing, China. We tested the
      hypothesis that nasal structure in these patients would correlate with
      objectively measured olfactory performance. Minimum cross-sectional area (MCA) of
      the nose was significantly correlated with SS composite score (r = 0.434, p <
      0.001), a result that was driven by two of the test's three components: olfactory
      threshold (OT) (r = 0.385, p = 0.001) and olfactory discrimination (OD) (r =
      0.370, p = 0.001) but not olfactory identification (OI) (p > 0.05). Additionally,
      nasal volume (NV) was associated with composite SS score (r = 0.350, p = 0.002),
      a finding driven by OT (r = 0.283, p = 0.014). These data suggest that nasal
      structure affects parameters of olfactory function, likely via alterations in
      nasal airflow. Thus, anatomic abnormalities and diseases involving airflow (such
      as OSA) may cause, in part, olfactory dysfunction that is amenable to treatment.
      We speculate that surgery that alters nasal volume and MCA may improve olfactory
      performance.

PMID- 24890979
TI  - High diastereoselection of a dissymmetric capsule by chiral guest complexation.
AB  - Encapsulation of chiral guests in the dissymmetric capsule 1?4 BF4 formed
      diastereomeric supramolecular complexes G?1?4 BF4 (G: guest). When chiral guests
      2 a-q were encapsulated within the dissymmetric space of the self-assembled
      capsule 1?4 BF4 , circular dichroism (CD) was observed at the absorption bands
      that are characteristic of the pi-pi* transition of the bipyridine moiety of the
      capsule, which suggests that the P and M helicities of the capsule are biased by
      the chiral guest complexation. The P helicity of diastereomeric complex (S)-2
      l?1?4 BF4 was determined to be predominant, based on CD exciton coupling theory
      and DFT calculations. The diastereoselectivity was highly influenced by the ester
      substituents, such that benzyl ester moieties were good for improving the
      diastereoselectivity. A diastereomeric excess of 98 % was achieved upon the
      complexation of 2 j. The relative enthalpic and entropic components for the
      distereoselectivity were obtained from a van't Hoff plot. The enthalpic
      components were linearly correlated with the substituent Hammett parameters
      (sigmap (+) ). The electron-rich benzyl ester moieties generated donor-acceptor
      pi-pi stacking interactions with the bipyridine moiety, which resulted in a
      significant difference in energy between the predominant and subordinate
      diastereomeric complexes. 

PMID- 24890977
TI  - Treatment of patients with anaplastic thyroid cancer during the last 20 years:
      whether any progress has been made?
AB  - Anaplastic thyroid cancer (ATC) is one of the most deadly cancers in humans.
      Searching a PubMed database, studies published during the last 20 years, 63
      publications dealing with treatment of patients were identified. Cohort studies
      comprised 6,609 patients with the median age 68 years (range 57-77 years). The
      median survival was 3.9 months, and 1 year survival, 20%. The median survival of
      patients treated with multimodal therapy was 10.5 months. There was significant
      difference in median survival (7.0 vs. 3.8 months; p < 0.05) and 1 year survival
      (30.5 vs. 16.8 months; p < 0.05) between the patients <68 and 68 or more years
      old. Clinical trials, both randomized and non-randomized, comprised 205 patients.
      Unfortunately, considerable improvement in the understanding of the pathogenesis
      and genetics of the ATC has not yet resulted in the improvement of the outcome of
      these patients.

PMID- 24890978
TI  - The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma.
AB  - The aim of this study was to determine the prognostic value of Ki-67
      immunostaining in patients affected by laryngeal squamous cell carcinoma. A
      systematic review was carried out in a tertiary university referral center. An
      appropriate string was run on PubMed to retrieve articles dealing with Ki-67
      immunohistochemical staining and laryngeal squamous cell carcinoma. A double
      cross-check was performed on citations and full-text articles by two
      investigators independently to review all manuscripts and perform a comprehensive
      quality assessment. Of 85 abstracts identified, 18 articles were included. These
      studies reported on 1,342 patients with histological confirmed diagnosis of
      laryngeal squamous cell carcinoma. Most studies showed a statistical association
      between Ki-67 immunohistochemical expression and at least one of the clinical and
      histopathological parameters considered by the authors. Overall the studies
      analyzed suggested that the tumoral proliferative index was statistically
      connected respectively with T stage (2/18), N stage (4/18), grading (6/18),
      disease-free survival (10/18) and overall survival (4/18). Our review strongly
      suggests that immunohistochemical staining of Ki-67 correlates with tumoral
      aggressiveness and worse prognosis in patients affected by laryngeal squamous
      cell carcinoma. Further high-quality prospective studies should be carried out to
      confirm our finding and determine the eventual differences between cancers of
      specific laryngeal subsites. 

PMID- 24890980
TI  - The value of second opinion in thyroid cytology: a review.
AB  - BACKGROUND: Second-opinion diagnosis (SOD) on pathological material is an
      accepted practice before definitive therapy is considered for referred patients.
      The thyroid gland is an anatomical site prone to diagnostic disagreement between
      pathologists. We performed a review of the literature that addressed the role of
      interinstitutional SOD on thyroid fine-needle aspirations (FNAs). METHODS: Nine
      studies comprising second opinions on thyroid FNAs were selected. The parameters
      analyzed included: discordances between the initial diagnoses (IDs) and SODs;
      cytohistologic correlation; changes in the clinical management of the patients
      with thyroid nodules after SOD. The same parameters were applied to the
      "indeterminate" diagnostic category comprising cases initially reported as
      "atypia," "atypia of undetermined significance/follicular lesion of undetermined
      significance," "suspicious for a follicular neoplasm," "follicular neoplasm,"
      "suspicious," and "suspicious for malignancy." RESULTS: A total of 7154 thyroid
      FNAs were retrieved, showing an overall discordance rate between ID and SOD of
      28.6%. In general, SOD was better supported by clinical follow-up and
      histological diagnosis, showing higher diagnostic accuracy in comparison with ID.
      Almost one-third (30.4%) of the discordant cases resulted in changes in the
      clinical management of patients with thyroid nodules. Numerous thyroid FNAs
      initially categorized as "indeterminate" were definitively classified as benign
      or malignant by SOD, with an overall diagnostic resolution rate of 42.5%,
      sensitivity of 97.9%, and diagnostic accuracy of 73.7%. CONCLUSIONS: Second
      opinion review of thyroid FNA improves diagnostic accuracy and potentially
      changes clinical management. SOD also demonstrates a significative rate of
      diagnostic resolution for thyroid FNAs originally diagnosed as "indeterminate."

PMID- 24890982
TI  - PAR-4: a possible new target for age-related disease.
AB  - INTRODUCTION: Apoptosis plays an important role in age-related disease, and
      prostate apoptosis response-4 (PAR-4) is a novel apoptosis-inducing factor that
      regulates apoptosis in most cells. Recent studies suggest that PAR-4 plays an
      important role in the progression of many age-related diseases. This review
      highlights the significance of PAR-4 and builds a strong case supporting its role
      as a possible therapeutic target in age-related disease. AREAS COVERED: This
      review covers the advancements over the last 15 years with respect to PAR-4 and
      its significance in age-related disease. Additionally, it provides knowledge
      regarding the significance of PAR-4 in age-related disease as well as its role in
      apoptotic signaling pathways, endoplasmic reticulum (ER) stress, and other
      mechanisms that may induce age-related disease. EXPERT OPINION: PAR-4 may be a
      potential therapeutic target that can trigger selective apoptosis in cancer
      cells. It is induced by ER stress and increased ER stress, and it is involved in
      the activity of the dopamine D2 receptor. Abnormal expression of PAR-4 may be
      associated with cardiovascular disease and diabetes. PAR-4 agonists and
      inhibitors must be identified before gene therapy can commence.

PMID- 24890983
TI  - Echocardiographic evaluation in transposition of the great arteries in the adult.
AB  - Transposition of the great arteries is marked by ventriculo-arterial discordance
      and occurs in 2 distinct subtypes. Echocardiography is the primary method of
      evaluating this condition in the adult. Key elements of the echocardiographic
      exam include confirming the diagnosis, evaluating ventricular size and function,
      assessing valvular regurgitation, identifying atrial baffle leaks or obstruction,
      estimating pulmonary artery pressures, and ruling out residual shunts. 

PMID- 24890981
TI  - Histological correlation of diffusional kurtosis and white matter modeling
      metrics in cuprizone-induced corpus callosum demyelination.
AB  - The cuprizone mouse model is well established for studying the processes of both
      demyelination and remyelination in the corpus callosum, and it has been utilized
      together with diffusion tensor imaging (DTI) to investigate myelin and axonal
      pathology. Although some underlying morphological mechanisms contributing to the
      changes in diffusion tensor (DT) metrics have been identified, the understanding
      of specific associations between histology and diffusion measures remains
      limited. Diffusional kurtosis imaging (DKI) is an extension of DTI that provides
      metrics of diffusional non-Gaussianity, for which an associated white matter
      modeling (WMM) method has been developed. The main goal of the present study was
      to quantitatively assess the relationships between diffusion measures and
      histological measures in the mouse model of cuprizone-induced corpus callosum
      demyelination. The diffusional kurtosis (DK) and WMM metrics were found to
      provide additional information that enhances the sensitivity to detect the
      morphological heterogeneity in the chronic phase of the disease process in the
      rostral segment of the corpus callosum. Specifically, in the rostral segment,
      axonal water fraction (d = 2.6; p < 0.0001), radial kurtosis (d = 2.0; p = 0.001)
      and mean kurtosis (d = 1.5; p = 0.005) showed the most sensitivity between groups
      with respect to yielding statistically significant p values and high Cohen's d
      values. These results demonstrate the ability of DK and WMM metrics to detect
      white mater changes and inflammatory processes associated with cuprizone-induced
      demyelination. They also validate, in part, the application of these new WMM
      metrics for studying neurological diseases, as well as helping to elucidate their
      biophysical meaning.

PMID- 24890984
TI  - Nurses' views of forensic care in emergency departments and their attitudes, and
      involvement of family members.
AB  - AIMS AND OBJECTIVES: To describe Nurses' views of forensic care provided for
      victims of violence and their families in EDs, to identify factors associated
      with Nurses' attitudes towards families in care and to investigate if these
      attitudes were associated with the involvement of patients' families in care.
      BACKGROUND: Interpersonal violence has serious health consequences for
      individuals and family members. Emergency departments provide care for victims of
      violence, and nurses play a key role in forensic care. However, there is limited
      knowledge of their views and their involvement of family members. DESIGN: A cross
      sectional design was used with a sample of all registered nurses (n = 867) in 28
      emergency departments in Sweden. METHODS: A self-report questionnaire, including
      the instrument Families' Importance in Nursing Care - Nurses' Attitudes, was used
      to collect data. Descriptive statistics, multiple linear regression and ordinal
      regression were used to analyse data. RESULTS: Four hundred and fifty-seven
      nurses completed the questionnaire (53%). Most nurses provided forensic care, but
      few had specific education for this task. Policy documents and routines existed
      for specific patient groups. Most nurses involved family members in care although
      education and policy documents rarely included them. Being a woman, policy
      documents and own experience of a critically ill family member were associated
      with a positive attitude towards family. A positive attitude towards family
      members was associated with involving patients' families in care. CONCLUSION:
      Many emergency department nurses provided forensic care without having specific
      education, and policy documents only concerned women and children. Nurses'
      positive attitude to family members was not reflected in policies or education.
      RELEVANCE TO CLINICAL PRACTICE: These results can inspire clinical forensic care
      interventions in emergency departments. Educational efforts for nurses and
      policies for all groups of victims of violence are needed. Emergency departments
      may need to rethink how family members are included in their organisation.

PMID- 24890985
TI  - Radiation-induced morphoea treated with UVA-1 phototherapy.
AB  - Morphoea is a localized inflammatory disorder of the dermis and subcutaneous fat
      and radiotherapy is a rarely reported cause (estimated incidence of 2 per 1000).
      Morphoea is commonly mistaken for an inflammatory recurrence of breast cancer,
      resulting in unnecessary investigations and treatment. We report the case of a 40
      year-old woman who developed radiation-induced morphoea of the breast 7 months
      following adjuvant radiotherapy. She was treated with topical and systemic
      steroids as well as psoralen plus ultraviolet (UV)A before proceeding to UVA1
      phototherapy. We also review the literature and discuss other management options.

PMID- 24890986
TI  - Meta-analysis of randomized clinical trials comparing bivalirudin versus heparin
      plus glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous
      coronary intervention and in patients with ST-segment elevation myocardial
      infarction.
AB  - This study sought to investigate the relative safety and efficacy of bivalirudin
      versus heparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing
      percutaneous coronary intervention (PCI) and in those with ST-segment elevation
      myocardial infarction (STEMI). The safety of bivalirudin in PCI, particularly in
      patients with STEMI, continues to be debated. We searched the on-line databases
      for randomized controlled trials of bivalirudin versus heparin plus GP IIb/IIIa
      inhibitors. Data on study design, inclusion and exclusion criteria, sample
      characteristics, and clinical outcomes at 30 days were extracted. A total of
      19,856 PCI patients included in 7 randomized trials and 5,820 patients with STEMI
      included in 2 randomized trials were separately analyzed. At 30 days, bivalirudin
      use in patients undergoing PCI resulted in similar rates of death, myocardial
      infarction, repeat revascularization, and stent thrombosis. In patients with
      STEMI, bivalirudin use resulted in decreased cardiac mortality (risk ratio [RR]
      0.70, 95% confidence interval [CI] 0.50 to 0.97, p=0.03) compared with heparin
      plus GP IIb/IIIa inhibitors but an increase in definite stent thrombosis at 30
      days (RR 1.88, 95% CI 1.09 to 3.24, p=0.02) driven by an increase in acute stent
      thrombosis (RR 5.48, 95% CI 2.30 to 13.07, p=0.0001). Bivalirudin use was
      associated with a decrease in Thrombolysis In Myocardial Infarction (TIMI) major
      (RR 0.58, 95% CI 0.46 to 0.74, p<0.0001) and TIMI minor (RR 0.55, 95% CI 0.48 to
      0.63, p<0.0001) bleeding rates in PCI patients as well as in a subgroup of
      patients with STEMI. In conclusion, in PCI patients anticoagulation with
      bivalirudin results in similar ischemic adverse events and a reduction in TIMI
      major and minor bleeding at 30 days compared with heparin plus GP IIb/IIIa
      inhibitors. In patients with STEMI, bivalirudin use is associated with a
      reduction in TIMI major and minor bleeding and fewer deaths from cardiac causes
      but an increase in acute and 30-day definite stent thrombosis.

PMID- 24890988
TI  - Switchable and selective detection of Zn2+ or Cd2+ in living cells based on 3'-O
      substituted arrangement of benzoxazole-derived fluorescent probes.
AB  - Two benzoxazole-derived ESIPT fluorescent sensors and show highly selective
      detection of Zn(2+) and Cd(2+), respectively, in aqueous solution and living
      cells. The selectivity switching from Zn(2+) to Cd(2+) is attributed to the
      different binding mode which is dependent on the 3'-O-substituted arrangement. 

PMID- 24890987
TI  - Symptoms and angiographic findings of patients undergoing elective coronary
      angiography without prior stress testing.
AB  - Many patients undergo elective coronary angiography without preprocedural stress
      testing that may be suitable if performed in patients with more angina pectoris
      or more frequently identified obstructive coronary artery disease (CAD). Patients
      in the National Cardiovascular Data Registry CathPCI Registry undergoing elective
      coronary angiography from July 2009 to April 2013 were assessed for differences
      in angina (Canadian Cardiovascular Society [CCS] class) and severity of
      obstructive CAD in those with and without preprocedural stress testing,
      stratified by CAD history. Given the large sample size, differences were
      considered clinically meaningful if the standardized difference (SD) was >10%. Of
      790,601 patients without CAD history, 36.9% did not undergo preprocedural stress
      testing. Compared with patients with preprocedural stress testing, patients
      without preprocedural stress testing were more frequently angina free (CCS class
      0; 28.2% with stress test vs 38.5% without, SD = 14.8%) and had similar rates of
      obstructive CAD (40.1% with stress test vs 35.7% without, SD = 9.0). Of 449,579
      patients with CAD history, 44.2% did not undergo preprocedural stress testing.
      Patients without preprocedural stress testing reported more angina (CCS class
      III/IV angina: 17.8% vs 13.4%; SD = 11.3%) but were not more likely to have
      obstructive CAD (78.7% vs 81.1%; SD = 5.8%) than patients with preprocedural
      stress testing. In conclusion, approximately 40% of patients undergoing elective
      coronary angiography did not have preprocedural risk stratification with stress
      testing. For these patients, the clinical decision to proceed directly to
      invasive evaluation was not driven primarily by severe angina and did not result
      in higher detection rates for obstructive CAD. 

PMID- 24890989
TI  - Visible-light-driven, tunable, photoelectrochemical performance of a series of
      metal-chelate, dye-organized, crystalline, CdS nanoclusters.
AB  - CdS nanoclusters of four different sizes were integrated with ruthenium-complex
      dyes. The cluster-dye crystalline composites, [Cd(4)(SPh)(10)][Ru(bpy)(3)],
      [Cd(8)S(SPh)(16)][Ru(bpy)(3)], [Cd(8)S(SPh)(13)
      ?Cl?(CH(3)OCS(2))(2)][Ru(phen)(3)], [Cd(17)S(4)(SPh)(28)][Ru(bpy)(3)], and
      [Cd(32)S(14)(SPh)(40)][Ru(phen)(3)](2) (phen=1,10-phenanthroline and
      bpy=bipyridine), show intense absorption in the visible-light region. They also
      exhibit size-dependent photocurrent responses under the illumination of visible
      light. The photocurrent increases with increased cluster size. The dyes also have
      significant influence on the photocurrent generation of the composite.

PMID- 24890990
TI  - Loading dose of fomepizole is safe in children with presumed toxic alcohol
      exposure - a case series.

PMID- 24890992
TI  - The effect of obesity on the clinical, functional and radiological outcome of
      cementless total hip replacement: a case-matched study with a minimum 10-year
      follow-up.
AB  - 1420 primary cementless THRs with a minimum follow-up of 10-years were stratified
      according to BMI: non-obese (BMI<30kg/m(2)) and obese (BMI>=30kg/m(2)). Median
      age at surgery was younger in obese patients (P<0.001). We case-matched 82 THRs
      in obese patients with 162 THRs in non-obese patients. No difference between
      groups was found in improvement in HHS (P=0.668), satisfaction with surgery
      (P=0.644), range of movement, prosthesis orientation, or radiological loosening.
      The obese cohort was further separated into those with a BMI below and above 35.
      No difference was found between groups in improvement in HHS, satisfaction with
      surgery, component orientation, or radiological loosening. There was no
      difference in the incidence of post-operative complications between obese and non
      obese patients. After 10-years, the results of THR are not compromised by
      obesity. 

PMID- 24890993
TI  - Predictivity and fate of metal ion release from metal-on-metal total hip
      prostheses.
AB  - Blood metal ion levels in 72 patients with large head metal-on-metal hip
      arthroplasty were studied to determine the correlation between the values
      measured in whole blood and urine. Urinary cobalt and chromium levels of 30MUg
      and 21MUg, respectively, adjusted to creatinine were found to correspond to the
      7MUg/l cut-off value that has been accepted in whole blood. Cobalt and chromium
      levels in whole blood and urine both significantly correlated with increased
      acetabular component inclination angle over 50 degrees and pain scores. There was
      no correlation with socket anteversion angle or femoral head diameter. The data
      support the use of urinary measurement of metal ions adjusted to creatinine to
      monitor patients with large head metal-on-metal total hip arthroplasty. 

PMID- 24890991
TI  - Pharmacotherapy in the aftermath of trauma; opportunities in the 'golden hours'.
AB  - Several lines of research have demonstrated that memories for fearful events
      become transiently labile upon re-exposure. Activation of molecular mechanisms is
      required in order to maintain retrieved information. This process is called
      reconsolidation. Targeting reconsolidation - as in exposure-based psychotherapy -
      offers therefore a potentially interesting tool to manipulate fear memories, and
      subsequently to treat disorders such as post-traumatic stress disorder (PTSD). In
      this paper we discuss the evidence for reconsolidation in rodents and humans and
      highlight recent studies in which clinical research on normal and abnormal fear
      extinction reduction of the expression of fear was obtained by targeting the
      process of reconsolidation. We conclude that reconsolidation presents an
      interesting opportunity to modify or alter fear and fear-related memories. More
      clinical research on normal and abnormal fear extinction is required. 

PMID- 24890994
TI  - National trends in the utilization of blood transfusions in total hip and knee
      arthroplasty.
AB  - Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are among the most
      common surgical procedures that necessitate blood transfusion. The purpose of
      this study was to examine the trends in the utilization of blood transfusions in
      THA and TKA in the US from 2000 to 2009 by analyzing the Nationwide Inpatient
      Sample (NIS). During the last decade, the allogeneic blood transfusion (ALBT)
      rate increased (THA: 11.2% to 19.1%, TKA: 7.7% to 12.4%), whereas the predonated
      autologous blood transfusion (PR-ABT) rate decreased (THA: 7.7% to 3.9%, TKA:
      6.1% to 2.4%) in primary unilateral THA and TKA patients in US hospitals. Overall
      blood transfusion rates remained stable over time in primary unilateral THA and
      TKA patients.

PMID- 24890995
TI  - Patient-specific instrumentation in total knee arthroplasty provides no
      improvement in component alignment.
AB  - Improved component alignment in TKA remains a commonly cited benefit of MRI based
      patient-specific instrumentation (PSI). We hypothesized that PSI would lead to
      improved alignment versus traditional instrumentation (TI) during primary TKA.
      Fifty-eight knees (54 patients) that underwent TKA with PSI were compared to 62
      knees that had previously undergone TKA with TI. Radiographs were evaluated for
      mechanical axis and alignment of the femoral and tibial components. Alignment was
      similar between the groups. However, the PSI group showed fewer knees in the
      target range for posterior tibial slope (PSI 38% vs. TI 61%, P=0.01) in addition
      to a trend for fewer knees in target range for femoral flexion (PSI 40% vs. TI
      56%, P=0.07). This study demonstrated no improvement in overall alignment and
      perhaps a worsening of the tibial slope. 

PMID- 24890996
TI  - Can post-cam function be replaced by addition of a third condyle in PS TKA?
AB  - The purpose of the study was to analyze the effectiveness of an additional ball
      and socket articulation in implanted knees and whether it can replicate post-cam
      function. Fifteen knees implanted with a cruciate substituting (CS) polyethylene
      without a post and ten knees implanted with a posterior stabilized (PS)
      polyethylene with a post were analyzed using 3D model fitting approach. Two types
      of designs showed similar posterior translation and similar axial rotation. Most
      of the contact points at the ball and socket joint stayed within the socket
      height for the PS group. This study indicates that the ball and socket joint is
      able to function as a replacement of the post-cam mechanism, which might serve as
      a new way to achieve posterior stability. 

PMID- 24890997
TI  - Italian version of University of California at Los Angeles (UCLA) Activity Score:
      cross-cultural adaptation.
AB  - Over the last 10 years, patient-oriented evaluations using questionnaires have
      become an important aspect of clinical outcome studies. Any questionnaire must be
      translated and culturally adapted in order to be used with different language
      groups, and the translated version must then be evaluated for reliability,
      validity and responsiveness which are fundamental attributes of any measurement
      tool. The aim of this study is the validation, translation and cross-cultural
      adaptation of the Italian version of UCLA activity Score, following the Guillemin
      criteria. The results show that our Italian version of the UCLA score has the
      following: reproducibility expressed as ICC=0.994, an internal consistency
      calculated as Spearman-Brown coefficient=0.754 and finally the construct validity
      has demonstrated a significant Pearson's correlation coefficient with other
      validated hip questionnaires.

PMID- 24890998
TI  - Greater prevalence of wound complications requiring reoperation with direct
      anterior approach total hip arthroplasty.
AB  - The purpose of this retrospective study was to compare wound complication rates
      between primary THAs performed via a posterior or direct anterior approach. From
      our prospective outcomes registry, we identified 1288 primary THAs performed via
      a posterior approach and 505 via a direct anterior approach. The direct anterior
      approach resulted in a significantly greater number of wound complications that
      required reoperation than the posterior approach (7/505 (1.4%) vs. 3/1,288
      (0.2%), P=0.007). As such, patients should be counseled on the potential
      increased risk of early wound complications with the direct anterior approach,
      and future research is needed to determine if alternative closure techniques can
      reduce the risk of wound complication. 

PMID- 24890999
TI  - Historical implant or current best standard? Minimum five year follow-up outcomes
      of cemented Thompson hemiarthroplasties.
AB  - UK NICE guidelines recommend abandoning the Thompson hemiarthroplasty (TH) in
      favour of a 'proven prosthesis' such as the Exeter Trauma Stem. The aim of this
      study was to assess the hip fracture treatment with the TH. Between 2002 and
      2006, 430 cemented THs were performed (minimum 5 year follow-up). Death rates at
      1 year and 5 years were 26.6% and 67.4% with low complication (Dislocation 1.4%)
      and revision rate (1.2%). The TH remains a reliable and proven implant in
      appropriate patients (over the age of 80, with low activity levels, low
      ambulatory status and who maybe cognitively impaired), due to low complication
      and revision rates. Modern implants may provide better function or longevity, but
      there is little evidence to support abandoning the TH.

PMID- 24891000
TI  - Letter to the editor on "Simultaneous bilateral knee arthroplasty in
      octogenarians: can it be safe and effective?".

PMID- 24891001
TI  - A 5-8 year retrospective follow-up of the C-stem AMT femoral component: patient
      reported outcomes and survivorship analysis.
AB  - We report midterm functional, radiographic and survivorship data for the
      cemented, triple taper C-stem AMT femoral component from a consecutive cohort of
      415 hip arthroplasties in 386 patients at a non-developer centre. Follow-up
      ranges were from 60 to 99 months, with a mean of 76 months. 32 hips were lost to
      follow-up. The median OHS was 40, median SF-12 mental component score (MCS) was
      50, and median SF-12 physical component score (PCS) was 39. At 99 months follow
      up, stem survivorship is 96.9% (95% confidence interval (CI) 82.5-99.5), and
      construct survivorship is 96.0% (95% CI 84.2-99.0). Adverse events such as calcar
      fracture, greater trochanter fracture and dislocation were rare at <1%. There
      have been no revisions for aseptic loosening.

PMID- 24891002
TI  - Predictors of allogeneic blood transfusion in total hip and knee arthroplasty in
      the United States, 2000-2009.
AB  - We examined the predictors of allogeneic blood transfusion (ALBT) in primary
      unilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA),
      analyzing the Nationwide Inpatient Sample between 2000 and 2009. Multivariate
      logistic regression analysis was performed. Significant predictors of ALBT in
      both THA and TKA included older age, female gender, race, weight loss, anemia,
      Elixhauser Comorbidity Score, hospital caseload, hospital region, and insurance
      status. No autologous-related blood transfusion was a significant predictor of
      ALBT in THA, however, not in TKA. We believe that the utilization of ALBT in THA
      and TKA can decrease by taking these factors into consideration for patient blood
      management before surgery. 

PMID- 24891003
TI  - Effect of microseparation and third-body particles on dual-mobility crosslinked
      hip liner wear.
AB  - Large heads have been recommended to reduce the risk of dislocation after total
      hip arthroplasty. One of the issues with larger heads is the risk of increased
      wear and damage in thin polyethylene liners. Dual-mobility liners have been
      proposed as an alternative to large heads. We tested the wear performance of
      highly crosslinked dual-mobility liners under adverse conditions simulating
      microseparation and third-body wear. No measurable increase in polyethylene wear
      rate was found in the presence of third-body particles. Microseparation induced a
      small increase in wear rate (2.9mm(3)/million cycles). A finite element model
      simulating microseparation in dual-mobility liners was validated using these
      experimental results. The results of our study indicate that highly crosslinked
      dual-mobility liners have high tolerance for third-body particles and
      microseparation. 

PMID- 24891005
TI  - Can spinal cord injury patients show a worsening in ASIA impairment scale
      classification despite actually having neurological improvement? The limitation
      of ASIA Impairment Scale Classification.
AB  - BACKGROUND: In our clinical training program, which includes probable American
      Spinal Injury Association impairment scale (AIS) grade changes in the event of
      recovery, we have noticed some confounding results regarding the AIS grading in
      spinal cord injury (SCI) patient case examples who are expected to recover. We
      also observed an individual case that showed a conflict between AIS grade
      conversion and neurological changes in European Multicenter Study on Human Spinal
      Cord Injury study. STUDY DESIGN: The analysis of SCI case examples for the
      probable AIS grade changes in the event of recovery. OBJECTIVES: To demonstrate
      the possible problems with AIS classification in SCI cases involving presumed
      motor and sensory changes, and to clarify the possible causes of the inverse
      relationship between the motor/sensory changes and AIS conversion in certain
      conditions. SETTING: Ankara, Turkey. METHODS: We studied the case examples of
      reference from the 2011 revision of International Standards for the Neurological
      Classification of Spinal Cord Injury. RESULTS: We encountered the same unique
      problem of deteriorating AIS grades within the critical zones of conversion when
      presumed neurological improvement took place, and vice versa. CONCLUSION: When
      recovery occurs without observing any motor or sensory changes while taking only
      the AIS into account, it would be possible to make an incorrect conclusion. This
      is most likely an indication of a limitation of the AIS. To enlighten this
      paradox, the large amount of data in SCI databases should be reanalyzed.

PMID- 24891004
TI  - Stockinette application over a non-prepped foot risks proximal contamination.
AB  - This study sought to determine if there was an increased risk for surgical site
      contamination during stockinette application for a lower extremity surgery
      draping technique. Utilizing a simulated, sterile surgical field, stockinettes
      were applied over 10 cadaver lower extremities that were contaminated with non
      pathogenic Escherichia coli on the foot. Of those, five specimens were then
      disinfected with Chloroprep and another 5 did not undergo any disinfection. All
      the specimens in which the stockinette was applied over a non-prepped foot showed
      proximal contamination. No contamination occurred in any of the specimens where
      the foot was disinfected. Stockinette can be a source of surgical site
      contamination when placed over a non-prepared foot. 

PMID- 24891006
TI  - Elevation of interleukin-6 and attenuation of tumor necrosis factor-alpha during
      wheelchair half marathon in athletes with cervical spinal cord injuries.
AB  - STUDY DESIGN: Nonrandomized study. OBJECTIVES: The purpose of this study was to
      determine the effects of long and intensive exercise on interleukin-6 (IL-6) and
      tumor necrosis factor-alpha (TNF-alpha) in athletes with cervical spinal cord
      injuries (CSCI). SETTING: The 30th Oita International Wheelchair Marathon Race.
      METHODS: Blood samples from six athletes with CSCI and eight athletes with
      thoracic and lumber spinal cord injuries (SCI) participating in wheelchair half
      marathon race were collected before the race, immediately after the race and 2 h
      after the race. IL-6, TNF-alpha, adrenaline and blood cell counts were measured.
      RESULTS: Monocyte count remained stable throughout the study in the CSCI group
      but was significantly high at 2 h after the race in the SCI group. Plasma IL-6
      concentrations were significantly elevated immediately after the race in both
      groups, although the levels in CSCI were significantly lower than in the SCI
      group. Plasma adrenaline was significantly elevated immediately after the race in
      the SCI group but recovered at 2 h after the race. In contrast, plasma adrenaline
      did not change in the CSCI group throughout the study and was significantly lower
      than in the SCI group. Plasma TNF-alpha did not change throughout the study in
      the SCI group compared with a significant decrease at 2 h after the race in the
      CSCI group. CONCLUSION: Long and intensive exercise increased IL-6 in the CSCI
      group despite the small muscle mass and lack of sympathetic nervous system. The
      post-race fall in plasma TNF-alpha in the CSCI group could be related to the
      inhibitory effect of rising IL-6 in the presence of normal monocyte count and
      stable adrenaline level.

PMID- 24891007
TI  - Sleep disruption in tetraplegia: a randomised, double-blind, placebo-controlled
      crossover trial of 3 mg melatonin.
AB  - STUDY DESIGN: Randomised, double-blind, placebo-controlled crossover trial of
      melatonin supplementation to people with complete tetraplegia. OBJECTIVES: To
      investigate the effect that 3 mg melatonin supplementation has on objective and
      subjective sleep, quality of life and mood of people living with complete
      tetraplegia. SETTING: Austin Hospital Sleep Laboratory and participants' homes,
      Melbourne, Victoria, Australia. METHODS: Two week run-in followed by 3 week
      nightly administration of 3 mg melatonin or placebo, 2-week washout and further 3
      week administration of the opposite treatment. Four testing sessions were
      conducted; the last nights of the run-in, treatment and washout periods. Testing
      sessions involved recording full polysomnography, completing a questionnaire
      battery and collecting urine and blood samples. The questionnaires assessed mood,
      sleep symptoms and health-related quality of life, and the urine and plasma
      samples assayed 6-sulphatoxymelatonin (aMT6s) and melatonin levels, respectively.
      A sleep diary was completed throughout the study. RESULTS: Eight participants
      (mean (s.d.): age 49.5 years (16), postinjury 16.9 years (7.1)) were recruited in
      which seven concluded the protocol. Endogenous-circulating melatonin was
      significantly higher (P < or = 0.01) following melatonin (urine: 152.94 MUg h(-1)
      (74.51), plasma: 43,554.57 pM (33,527.11)) than placebo (urine: 0.86 MUg h(-1)
      (0.40), plasma: 152.06 pM (190.55)). Subjective sleep improved significantly
      following melatonin specifically for duration of sleep per night and
      psychological wellbeing. Objective sleep showed a significant increase in light
      sleep with melatonin, with all other sleep parameters being unchanged.
      CONCLUSION: These results suggest that increasing melatonin in people with
      complete tetraplegia is beneficial, especially for subjective sleep.
      Investigation of the pharmacokinetics of melatonin metabolism in this population
      is warranted. SPONSORSHIP: This project is proudly supported by the Transport
      Accident Commission.

PMID- 24891008
TI  - A six-week motor-driven functional electronic stimulation rowing program improves
      muscle strength and body composition in people with spinal cord injury: a pilot
      study.
AB  - STUDY DESIGN: Preclinical and postclinical intervention and outcomes measure
      design. OBJECTIVE: To investigate the efficacy of six weeks of motor-driven
      functional electronic stimulation (FES) rowing exercise intervention on
      cardiopulmonary fitness, upper body strength and body composition in people with
      spinal cord injury (SCI). SETTING: The National Rehabilitation Center in Korea.
      METHODS: A total of 12 people with SCI (ten males, two females) participated in
      42.5-minute training sessions on motor-driven FES rowing machine, 5 days a week
      for 6 weeks. Peak oxygen consumption, body mass index, percent body fat, waist
      circumference, shoulder abduction and adduction, shoulder flexion and extension
      and elbow flexion and extension were measured at baseline and after the
      intervention. RESULTS: The six weeks of training with a motor-driven FES rowing
      machine significantly decreased percent body fat (Pre: 23.9+/-8.5 vs. Post:
      20.4+/-7.9, P=0.028) and increased lean body mass (Pre: 50.4+/-9.4 vs. Post:
      53.3+/-10.0, P=0.001), muscular strength of the shoulder flexors (Pre: 147.5+/
      68.5 vs. Post: 180.9+/-71.8, P=0.002), extensors (Pre: 132.7+/-51.8 vs. Post:
      160.6+/-67.9, P=0.010), abductors (Pre: 126.1+/-52.6 vs. Post: 163.7+/-77.8,
      P=0.002) and adductors (Pre: 172.3+/-69.0 vs. Post: 215.2+/-95.7, P=0.003), as
      well as elbow flexors (Pre: 212.7+/-66.6 vs. Post: 256.6+/-76.1, P=0.004) and
      extensors (Pre: 190.6+/-65.0 vs. Post: 221.9+/-63.9, P=0.002). CONCLUSIONS:
      Exercise using a motor-driven FES rowing machine may be used as a new exercise
      modality to improve body composition and upper body muscle strength in people
      with SCI. SPONSORSHIP: This research was supported by a grant (code# 08-B-03, #10
      B-01) from the National Rehabilitation Research Institute.

PMID- 24891009
TI  - Circulating microRNAs as biomarkers for evaluating the severity of acute spinal
      cord injury.
AB  - STUDY DESIGN: An in vivo study in mouse models of spinal cord contusion.
      OBJECTIVES: To develop a novel indicator to anticipate the severity of spinal
      cord injury (SCI) during the acute phase and for the assessment of the efficacy
      of novel therapies. MicroRNAs (miRNAs) circulating in the peripheral blood are
      reported to modulate signaling between cells, and to be diagnostic markers for
      cancers. The purpose of this study was to identify circulating miRNAs for
      predicting the severity of SCI in the acute phase. SETTING: Department of
      Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima
      University, Hiroshima, Japan. METHODS: Mouse SCI models were made using Infinite
      Horizon impactor with 50 or 70 kdyn compressing power following thoracic
      laminectomy. The mice were then divided into four groups: normal (without
      surgery), sham (laminectomy only), mild (50 kdyn), and severe (70 kdyn). TaqMan
      low-density array analysis and real-time PCR were performed to identify candidate
      miRNAs that were increased in the serum relative to the severity of SCI. RESULTS:
      The expression levels of miR-9*, miR-219 and miR-384-5p in the serum were
      significantly increased relative to the severity of SCI 12 h after injury. The
      expression of miR-9* was also significantly increased relative to injury severity
      at 3 and 24 h after injury. CONCLUSION: Serum miR-9*, miR-219 and miR-384-5p
      might be promising biomarkers for predicting the severity of SCI.

PMID- 24891010
TI  - Cardiorespiratory responses during functional electrical stimulation cycling and
      electrical stimulation isometric exercise.
AB  - STUDY DESIGN: Prospective experimental. OBJECTIVES: To compare the
      cardiorespiratory responses with electrical stimulation (ES) producing either
      dynamic leg cycling or intermittent isometric leg contractions using the same ES
      protocol. SETTING: Sydney, Australia. METHODS: Eight paraplegics (T4-T11)
      performed ES exercise sessions on two separate days. On day 1, cardiorespiratory
      responses were measured during 5 min of rest followed by 35 min of cycling, and
      finally 15 min of intermittent isometric exercise using the same ES parameters.
      On the second day, after 5 min of rest, 35 min of isometric exercise was
      performed followed by 15 min of cycling. RESULTS: There were no significant
      differences during the first 35 min of exercise on each day comparing the two
      modes of exercise for average rate of oxygen consumption (cycling, 534+/-128 ml
      min(-1); isometric 558+/-146 ml min(-1); P=0.451), the average heart rate
      (cycling, 93+/-15 b.p.m.; isometric 95+/-17 b.p.m.; P=0.264) or minute
      ventilation (cycling, 23.0+/-6.5 l min(-1); isometric 23.8+/-6.7 l min(-1);
      P=0.655). In addition, there were no significant differences between exercise
      modes for any peak cardiorespiratory values recorded during the initial 35 min of
      exercise or the following 15 min crossover exercise phase. CONCLUSION: The
      current data found that intermittent ES leg isometric exercise elicited a similar
      cardiorespiratory response compared with functional ES leg cycling, suggesting it
      should be investigated as a viable alternative intervention for increasing whole
      body metabolic rate during sustained exercise training sessions for individuals
      with paralyzed muscles.

PMID- 24891011
TI  - Responsiveness and concurrent validity of the revised capabilities of upper
      extremity-questionnaire (CUE-Q) in patients with acute tetraplegia.
AB  - STUDY DESIGN: This is a longitudinal convenience sample. OBJECTIVE: The objective
      of this study was to evaluate the responsiveness of the revised Capabilities of
      Upper Extremity-Questionnaire (CUE-Q), in which the item responses were reduced
      from seven to five levels, relative to the upper extremity motor score (UEMS) and
      to the self-care subscale of Functional Independence Measure (FIMsc). METHODS: A
      total of 46 subjects with acute traumatic tetraplegia, 19 motor complete, 27
      motor incomplete, completed the revised CUE-Q, UEMS and FIMsc at admission and
      discharge from rehabilitation. RESULTS: Subjects were mostly male (n=42) and
      Caucasian (n=27). The mean age was 44+/-21 years. Predominant etiologies were
      falls (n=18) and motor vehicle accidents (n=17). During rehabilitation, mean CUE
      Q scores increased from 49.8+/-30.8 to 73.7+/-36.3, UEMS increased from 19.6+/
      11.9 to 26.3+/-13.4, and FIMsc increased from 9.8+/-5.1 to 21.5+/-9.7. At
      admission and discharge, CUE scores had excellent to good Spearman correlations
      (rs) with UEMS (rs=0.89, 0.70) and FIMsc (rs=0.73, 0.80), but change scores had
      little to moderate correlations (CUE-UEMS, rs=0.07; CUE-FIMsc, rs=0.51),
      suggesting that the CUE, UEMS and FIM measure related but different constructs.
      Effect size of the change score was 0.92 for CUE-Q, 0.87 for UEMS and 1.38 for
      FIMsc. This compares to an effect size of 0.73 for the original 7-level response
      CUE-Q. CONCLUSION: The simplified response set of the CUE-Q maintains the
      responsiveness of the original version, whereas it increases the ease of use for
      the patient.

PMID- 24891012
TI  - International spinal cord injury upper extremity basic data set.
AB  - OBJECTIVE: To develop an International Spinal Cord Injury (SCI) Upper Extremity
      Basic Data Set as part of the International SCI Data Sets, which facilitates
      consistent collection and reporting of basic upper extremity findings in the SCI
      population. SETTING: International. METHODS: A first draft of a SCI Upper
      Extremity Data Set was developed by an international working group. This was
      reviewed by many different organisations, societies and individuals over several
      months. A final version was created. VARIABLES: The final version of the
      International SCI Upper Extremity Data Set contains variables related to basic
      hand-upper extremity function, use of assistive devices, SCI-related
      complications to upper extremity function and upper extremity/hand reconstructive
      surgery. Instructions for data collection and the data collection form are freely
      available on the ISCoS website (www.iscos.org.uk). CONCLUSION: The International
      SCI Upper Extremity Basic Data Set will facilitate consistent collection and
      reporting of basic upper extremity findings in the SCI population.

PMID- 24891013
TI  - Intolerance of uncertainty, cognitive complaints, and cancer-related distress in
      prostate cancer survivors.
AB  - OBJECTIVE: Prostate cancer survivors have reported cognitive complaints following
      treatment, and these difficulties may be associated with survivors' ongoing
      cancer-related distress. Intolerance of uncertainty may exacerbate this
      hypothesized relationship by predisposing individuals to approach uncertain
      situations such as cancer survivorship in an inflexible and negative manner. We
      investigated whether greater cognitive complaints and higher intolerance of
      uncertainty would interact in their relation to more cancer-related distress
      symptoms. METHODS: This cross-sectional, questionnaire-based study included 67
      prostate cancer survivors who were 3 to 5 years post treatment. Hierarchical
      multiple regression analyses tested the extent to which intolerance of
      uncertainty, cognitive complaints, and their interaction were associated with
      cancer-related distress (measured with the Impact of Event Scale-Revised; IES-R)
      after adjusting for age, education, physical symptoms, and fear of cancer
      recurrence. RESULTS: Intolerance of uncertainty was positively associated with
      the IES-R avoidance and hyperarousal subscales. More cognitive complaints were
      associated with higher scores on the IES-R hyperarousal subscale. The interaction
      of intolerance of uncertainty and cognitive complaints was significantly
      associated with IES-R intrusion, such that greater cognitive complaints were
      associated with greater intrusive thoughts in survivors high in intolerance of
      uncertainty but not those low in it. CONCLUSIONS: Prostate cancer survivors who
      report cognitive difficulties or who find uncertainty uncomfortable and
      unacceptable may be at greater risk for cancer-related distress, even 3 to 5
      years after completing treatment. It may be beneficial to address both cognitive
      complaints and intolerance of uncertainty in psychosocial interventions.

PMID- 24891014
TI  - Micro-organisms in latex and natural rubber coagula of Hevea brasiliensis and
      their impact on rubber composition, structure and properties.
AB  - Natural rubber, produced by coagulation of the latex from the tree Hevea
      brasiliensis, is an important biopolymer used in many applications for its
      outstanding properties. Besides polyisoprene, latex is rich in many nonisoprene
      components such as carbohydrates, proteins and lipids and thereby constitutes a
      favourable medium for the development of micro-organisms. The fresh rubber
      coagula obtained by latex coagulation are not immediately processed, allowing the
      development of various microbial communities. The time period between tree
      tapping and coagula processing is called maturation, during which an evolution of
      the properties of the corresponding dry natural rubber occurs. This evolution is
      partly related to the activity of micro-organisms and to the modification of the
      biochemical composition. This review synthesizes the current knowledge on
      microbial populations in latex and natural rubber coagula of H. brasiliensis and
      the changes they induce on the biochemistry and technical properties of natural
      rubber during maturation.

PMID- 24891016
TI  - Abnormal cervical cancer screening in pregnancy and preterm delivery.
AB  - BACKGROUND: Preterm delivery is a major cause of neonatal morbidity and
      mortality. Human papillomavirus (HPV) infection is common in reproductive-aged
      women. We hypothesised that abnormal cervical cancer screening tests, as a proxy
      for HPV infection, would be associated with preterm delivery. METHODS: We
      conducted a retrospective cohort study of women delivering liveborn singletons
      beyond 20 weeks gestation, who had a Papanicolaou (Pap) test within 1 year prior
      to delivery. Women with abnormal Pap or positive high-risk HPV tests, classified
      as having 'abnormal screening', were compared with women classified as having
      'normal screening' in bivariate analysis for overall preterm delivery at less
      than 37 weeks gestation. Using Poisson regression, we report unadjusted (RR) and
      adjusted (aRR) risk ratios for spontaneous preterm delivery due to preterm labour
      and preterm premature rupture of membranes. RESULTS: Among 2686 women meeting
      criteria for analysis, 213 (8%) had abnormal screening. Women with abnormal
      screening, compared with normal screening, were not more likely to deliver
      preterm (12.2% vs. 9.8%, RR 1.3 [95% confidence interval (CI) 0.9, 1.8], aRR 1.2
      [95% CI 0.8, 1.7]). Women with abnormal screening, however, were at greater risk
      for spontaneous preterm delivery in unadjusted and adjusted analysis (8.9% vs.
      4.5%; RR 2.0 [95% CI 1.2, 3.2], aRR 1.8 [95% CI 1.1, 2.9]). CONCLUSIONS: There
      was no difference in risk of overall preterm delivery in women with abnormal
      compared with normal cervical cancer screening tests. Our data suggest, however,
      that abnormal screening in pregnancy may be associated with spontaneous preterm
      delivery.

PMID- 24891015
TI  - Inhibition of calcineurin combined with dasatinib has direct and indirect anti
      leukemia effects against BCR-ABL1(+) leukemia.
AB  - Treatment of BCR-ABL1(+) leukemia has been revolutionized with the development of
      tyrosine kinase inhibitors. However, patients with BCR-ABL1(+) acute
      lymphoblastic leukemia and subsets of patients with chronic myeloid leukemia are
      at high risk of relapse despite kinase inhibition therapy, necessitating novel
      treatment strategies. We previously reported synthetic lethality in BCR-ABL1(+)
      leukemia cells by blocking both calcineurin/NFAT signaling and BCR-ABL1,
      independent of drug efflux inhibition by cyclosporine. Here, using RNA
      interference we confirm that calcineurin inhibition sensitizes BCR-ABL1(+) cells
      to tyrosine kinase inhibition in vitro. However, when we performed
      pharmacokinetic and pharmacodynamic studies of dasatinib and cyclosporine in
      mice, we found that co-administration of cyclosporine increases peak
      concentrations and the area under the curve of dasatinib, which contributes to
      the enhanced disease control. We also report the clinical experience of two
      subjects in whom we observed more hematopoietic toxicity than expected while
      enrolled in a Phase Ib trial designed to assess the safety and tolerability of
      adding cyclosporine to dasatinib in humans. Thus, the anti-leukemia benefit of co
      administration of cyclosporine and dasatinib is mechanistically pleiotropic, but
      may not be tolerable, at least as administered in this trial. These data
      highlight some of the challenges associated with combining targeted agents to
      treat leukemia.

PMID- 24891017
TI  - Cathepsin S inhibition lowers blood glucose levels in mice.
AB  - AIMS/HYPOTHESIS: Cathepsin S (CatS) belongs to a family of proteases that have
      been implicated in several disease processes. We previously identified CatS as a
      protein that is markedly overexpressed in adipose tissue of obese individuals and
      downregulated after weight loss and amelioration of glycaemic status induced by
      gastric bypass surgery. This prompted us to test whether the protease contributes
      to the pathogenesis of type 2 diabetes using mouse models with CatS inactivation.
      METHODS: CatS knockout mice and wild-type mice treated with orally active small
      molecule CatS inhibitors were fed chow or high-fat diets and explored for change
      in glycaemic status. RESULTS: CatS deletion induced a robust reduction in blood
      glucose, which was preserved in diet-induced obesity and with ageing and was
      recapitulated with CatS inhibition in obese mice. In vivo testing of glucose
      tolerance, insulin sensitivity and glycaemic response to gluconeogenic substrates
      revealed that CatS suppression reduced hepatic glucose production despite there
      being no improvement in insulin sensitivity. This phenotype relied on
      downregulation of gluconeogenic gene expression in liver and a lower rate of
      hepatocellular respiration. Mechanistically, we found that the protein 'regulated
      in development and DNA damage response 1' (REDD1), a factor potentially
      implicated in reduction of respiratory chain activity, was overexpressed in the
      liver of mice with CatS deficiency. CONCLUSIONS/INTERPRETATION: Our results
      revealed an unexpected metabolic effect of CatS in promoting pro-diabetic
      alterations in the liver. CatS inhibitors currently proposed for treatment of
      autoimmune diseases could help to lower hepatic glucose output in obese
      individuals at risk for type 2 diabetes.

PMID- 24891018
TI  - Mortality after cancer among patients with diabetes mellitus: effect of diabetes
      duration and treatment: (questionable) classification of diabetic patients based
      on combination of specific glucose-lowering drugs.

PMID- 24891019
TI  - Hyperglucagonaemia analysed by glucagon sandwich ELISA: nonspecific interference
      or truly elevated levels?
AB  - AIM/HYPOTHESIS: Hyperglucagonaemia is a characteristic of several clinical
      conditions (e.g. end-stage renal disease (ESRD), type 2 diabetes, obesity before
      and after Roux-en-Y gastric bypass (RYGB) and vagotomy with pyloroplasty), but
      the molecular nature of 'immunoreactive' glucagon is poorly characterised. The
      specific determination of fully processed, intact glucagon requires a 'sandwich'
      assay employing a combination of antibodies directed against both N- and C
      termini. We compared a novel assay for intact glucagon with a highly sensitive C
      terminal RIA (hitherto considered specific) to determine the extent to which the
      hyperglucagonaemia measured in clinical samples was caused by authentic glucagon.
      METHODS: We examined the performance of three commercial glucagon 'sandwich'
      ELISAs. The ELISA with the best overall performance was selected to compare
      glucagon measurements in clinical samples with an established glucagon RIA.
      RESULTS: The first assay performed poorly: there was high cross-reactivity with
      glicentin (22%) and a lack of sensitivity for glucagon. The second and third
      assays showed minor cross-reactivity (1-5%) with oxyntomodulin and glicentin;
      however, the second assay had insufficient sensitivity for glucagon in plasma
      (>10-20 pmol/l). Thus, only the third assay was suitable for measuring glucagon
      concentrations in clinical samples. The ELISA and RIA measured similar glucagon
      levels in healthy individuals. Measurements of samples from individuals with
      abnormally high (type 2 diabetes or obese) or very elevated (post vagotomy with
      pyloroplasty, post-RYGB) glucagon levels were also similar in both assays.
      However, glucagon levels in participants with ESRD were much lower when measured
      by ELISA than by RIA, indicating that the apparent hyperglucagonaemia is not
      caused by fully processed intact glucagon. CONCLUSIONS/INTERPRETATION: For most
      purposes, sensitive C-terminal glucagon RIAs are accurate. However, measurements
      may be spuriously high, at least in patients with renal disease. Trial
      Registration Samples from type 2 diabetic and normoglucose-tolerant patients
      before and 1 year after RYGB were from a study by Bojsen-Moller et al (trial
      registration number NCT 01202526). Samples from vagotomised and control
      individuals were from a study by Plamboeck et al (NCT01176890). Samples from ESRD
      patients were from a study by Idorn et al (NCT01327378).

PMID- 24891020
TI  - Eighteen year weight trajectories and metabolic markers of diabetes in
      modernising China.
AB  - AIMS/HYPOTHESIS: Although obesity is a major risk factor for diabetes, little is
      known about weight gain trajectories across adulthood, and whether they are
      differentially associated with metabolic markers of diabetes. METHODS: We used
      fasting blood samples and longitudinal weight data for 5,436 adults (5,734
      observations, aged 18-66 years) from the China Health and Nutrition Survey (1991
      2009). Using latent class trajectory analysis, we identified different weight
      gain trajectories in six age and sex strata, and used multivariable general
      linear mixed effects models to assess elevated metabolic markers of diabetes
      (fasting glucose, HbA1c, HOMA-IR, insulin) across weight trajectory classes.
      Models were fitted within age and sex strata, and controlled for baseline weight
      (or baseline weight by weight trajectory interaction terms), height, and smoking
      habit, with random intercepts to control for community-level correlations.
      RESULTS: Compared with weight gain, classes with weight maintenance, weight loss,
      or a switch from weight gain to loss had lower values for metabolic markers of
      diabetes. These associations were stronger among younger women (aged 18-29 and 30
      39 years) and men (18-29 years) than in older (40-66 years) men and women. An
      exception was HOMA-IR, which showed class differences across all ages (at least p
      < 0.004). CONCLUSION: Trajectory analysis identified heterogeneity in adult
      weight gain associated with diabetes-related metabolic markers, independent of
      baseline weight. Our findings suggest that variation in metabolic markers of
      diabetes across patterns of weight gain is masked by a homogeneous classification
      of weight gain.

PMID- 24891021
TI  - Surrogate measures of insulin sensitivity vs the hyperinsulinaemic-euglycaemic
      clamp: a meta-analysis.
AB  - AIMS/HYPOTHESIS: We aimed to identify which surrogate index of insulin
      sensitivity has the strongest correlation with the reference measurement, the
      hyperinsulinaemic-euglycaemic clamp (HEC), to determine which surrogate measure
      should be recommended for use in large-scale studies. METHODS: A literature
      search (1979-2012) was conducted to retrieve all articles reporting bivariate
      correlations between the HEC and surrogate measures of insulin sensitivity (in
      fasting samples or during the OGTT). We performed a random effects meta-analysis
      for each surrogate measure to integrate the correlation coefficients of the
      different studies. RESULTS: The OGTT-based surrogate measures with the strongest
      pooled correlations (r) to the HEC were the Stumvoll metabolic clearance rate
      (Stumvoll MCR; r = 0.70 [95% CI 0.61, 0.77], n = 5), oral glucose insulin
      sensitivity (OGIS; r = 0.70 [0.57, 0.80], n = 6), the Matsuda index (r = 0.67
      [0.61, 0.73], n = 19), the Stumvoll insulin sensitivity index (Stumvoll ISI; r =
      0.67 [0.60, 0.72], n = 8) and the Gutt index (r = 0.65 [0.60, 0.69], n = 6). The
      fasting surrogate indices that correlated most strongly with the HEC and had
      narrow 95% CIs were the revised QUICKI (r = 0.68 [0.58, 0.77], n = 7), the QUICKI
      (r = 0.61 [0.55, 0.65], n = 35), the log HOMA-IR (r = -0.60 [-0.66, -0.53], n =
      22) and the computer generated HOMA of insulin sensitivity (HOMA-%S; r = 0.57
      [0.46, 0.67], n = 5). CONCLUSIONS/INTERPRETATION: The revised QUICKI fasting
      surrogate measure appears to be as good as the OGTT-based Stumvoll MCR, OGIS,
      Matsuda, Stumvoll ISI and Gutt indices for estimating insulin sensitivity. It can
      therefore be recommended as the most appropriate index for use in large-scale
      clinical studies.

PMID- 24891029
TI  - Preliminary evidence of cognitive and brain abnormalities in uncomplicated
      adolescent obesity.
AB  - OBJECTIVE: To ascertain whether pediatric obesity without clinically significant
      insulin resistance (IR) impacts brain structure and function. METHODS: Thirty
      obese and 30 matched lean adolescents, all without clinically significant IR or a
      diagnosis of metabolic syndrome (MetS), received comprehensive endocrine,
      neuropsychological, and MRI evaluations. RESULTS: Relative to lean adolescents,
      obese non-IR adolescents had significantly lower academic achievement (i.e.,
      arithmetic and spelling) and tended to score lower on working memory, attention,
      psychomotor efficiency, and mental flexibility. In line with our prior work on
      adolescent MetS, memory was unaffected in uncomplicated obesity. Reductions in
      the thickness of the orbitofrontal and anterior cingulate cortices as well as
      reductions of microstructural integrity in major white matter tracts without
      gross volume changes were also uncovered. CONCLUSIONS: It was documented, for the
      first time, that adolescents with uncomplicated obesity already have subtle brain
      alterations and lower performance in selective cognitive domains. When
      interpreting these preliminary data in the context of our prior reports of
      similar, but more extensive brain findings in obese adolescents with MetS and
      T2DM, it was concluded that "uncomplicated" obesity may also result in subtle
      brain alterations, suggesting a possible dose effect with more severe metabolic
      dysregulation giving rise to greater abnormalities.

PMID- 24891030
TI  - Management of acute stroke in patients taking novel oral anticoagulants.
AB  - Each year, 1.0-2.0% of individuals with atrial fibrillation and 0.1-0.2% of those
      with venous thromboembolism who are receiving one of the novel oral
      anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to
      experience an acute ischemic stroke. Additionally, 0.2-0.5% of individuals with
      atrial fibrillation who are receiving one of the novel oral anticoagulants can be
      expected to experience an intracranial hemorrhage. This opinion piece addresses
      the current literature and offers practical approaches to the management of
      patients receiving novel oral anticoagulants who present with an ischemic or
      hemorrhagic stroke. Specifically, we discuss the role of thrombolysis in
      anticoagulated patients with acute ischemic stroke and factors to consider
      concerning restarting anticoagulation after acute ischemic and hemorrhagic
      stroke. 

PMID- 24891032
TI  - Optimization of extraction of bioactive compounds from different types of grape
      pomace produced at wineries and distilleries.
AB  - Natural extracts obtained from grape pomace are particularly interesting, due to
      the substantial variety of valuable compounds present with health benefits,
      specifically phenolic compounds such as anthocyanins, trans-resveratrol,
      quercetin, and proanthocyanidins. The production of such extracts has been
      recognized as a profitable way to valorize grape byproducts, which are low-value
      and most abundant. First, the effect of the solvent on the extraction of
      bioactive compounds from grape pomace is studied. The selected solvents are water
      and ethanol, biocompatible and available in wineries and distilleries. Then,
      different types of grape pomace obtained along the various stages of current
      industrial winemaking and distillation processes are analyzed. As a result, the
      best stage of the winemaking and distillation processes for pomace valorization
      is identified, corresponding to the grape byproduct with the highest potential as
      source of bioactive compounds. These studies were performed with Vitis vinifera
      variety of Tempranillo grapes (same year, same vineyard). PRACTICAL APPLICATION:
      This work optimizes the production of natural extracts from (byproduct) grape
      pomace with recognized health benefits, to be used as high value nutraceuticals
      ingredients. The process proposed uses renewable and low-cost resources existent
      in wineries and distilleries. The select solvent extracting is a mixture of the
      biocompatible water and ethanol. The selected fermented grape pomace was chosen
      from different and comparable types of grape pomace obtained at current
      winemaking and distillation processes, to be used in extraction without any
      pretreatment.

PMID- 24891031
TI  - The role of hermaphrodites in the experimental evolution of increased outcrossing
      rates in Caenorhabditis elegans.
AB  - BACKGROUND: Why most organisms reproduce via outcrossing rather than selfing is a
      central question in evolutionary biology. It has long ago been suggested that
      outcrossing is favoured when it facilitates adaptation to novel environments. We
      have previously shown that the experimental evolution of increased outcrossing
      rates in populations of the male-hermaphrodite nematode Caenorhabditis elegans
      were correlated with the experimental evolution of increased male fitness.
      However, it is unknown whether outcrossing led to adaptation, and if so, which
      fitness components can explain the observed increase in outcrossing rates.
      RESULTS: Using experimental evolution in six populations with initially low
      standing levels of genetic diversity, we show with head-to-head competition
      assays that population-wide fitness improved during 100 generations. Since
      outcrossing rates increased during the same period, this result demonstrates that
      outcrossing is adaptive. We also show that there was little evolution of
      hermaphrodite fitness under conditions of selfing or under conditions of
      outcrossing with unrelated tester males. We nonetheless find a positive genetic
      correlation between hermaphrodite self-fitness and population-wide fitness, and a
      negative genetic correlation between hermaphrodite mating success and population
      wide fitness. These results suggest that the several hermaphrodite traits
      measured are fitness components. Tradeoffs expressed in hermaphrodites,
      particularly noticed between self-fitness and mating success, may in turn explain
      their lack of change during experimental evolution. CONCLUSIONS: Our findings
      indicate that outcrossing facilitates adaptation to novel environments. They
      further indicate that the experimental evolution of increased outcrossing rates
      depended little on hermaphrodites because of fitness tradeoffs between selfing
      and outcrossing. Instead, the evolution of increased outcrossing rates appears to
      have resulted from unhindered selection on males.

PMID- 24891033
TI  - Stress, Cognitive Appraisal and Psychological Health: Testing Instruments for
      Health Professionals.
AB  - The job of health professionals, including nurses, is considered inherently
      stressful, and thus, it is important to improve and develop specific measures
      that are sensitive to the demands that health professionals face. This study
      analysed the psychometric properties of three instruments that focus on the
      professional experiences of nurses in aspects related to occupational stress,
      cognitive appraisal and mental health issues. The evaluation protocol included
      the Stress Questionnaire for Health Professionals (SQHP), the Cognitive Appraisal
      Scale (CAS) and the General Health Questionnaire-12 (GHQ-12). Validity and
      reliability issues were considered with statistical analysis (i.e., confirmatory
      factor analysis, convergent validity and composite reliability) that revealed
      adequate values for all of the instruments, namely a six-factor structure for the
      SQHP, a five-factor structure for the CAS and a two-factor structure for the GHQ
      12. In conclusion, this study proposes three consistent instruments that may be
      useful for analysing nurses' adaptation to work contexts.

PMID- 24891034
TI  - Velocity gap mode of capillary electrophoresis developed for high-resolution
      chiral separations.
AB  - A new CE method based on velocity gap (VG) theory has been developed for high
      resolution chiral separations. In VG, two consecutive electric fields are adopted
      to drive analytes passing through two capillaries, which are linked together
      through a joint. The joint is immersed inside another buffer vial which has
      conductivity communication with the buffer inside the capillary. By adjusting the
      field strengths onto the two capillaries, it is possible to observe different
      velocities of an analyte when it passes through those two capillaries and there
      would be a net velocity change (NVC) for the same analyte. Different analytes may
      have different NVC which may be specifically meaningful for enantioseparations
      because enantiomers are usually hard to resolve. By taking advantage of this NVC,
      it is possible to enhance the resolution of a chiral separation if a proper
      voltage program is applied. The feasibility of using NVC to enhance chiral
      separation was demonstrated in the separations of three pairs of enantiomers:
      terbutaline, chlorpheniramine, and promethazine. All separations started with
      partial separation in a conventional CE and were significantly improved under the
      same experimental conditions. The results indicated that VG has the potential to
      be used to improve the resolving power of CE in chiral separations. 

PMID- 24891035
TI  - Re: clinical identifiers for detecting underlying closed cervical fractures.

PMID- 24891036
TI  - Effect of bone fragment impact velocity on biomechanical parameters related to
      spinal cord injury: a finite element study.
AB  - Several experimental and computational studies have investigated the effect of
      bone fragment impact on the spinal cord during trauma. However, the effect of the
      impact velocity of a fragment generated by a burst fracture on the stress and
      strain inside the spinal cord has not been computationally investigated, even
      though spinal canal occlusion and peak pressure at various impact velocities were
      provided in experimental studies. These stresses and strains are known factors
      related to clinical symptoms or injuries. In this study, a fluid-structure
      interaction model of the spinal cord, dura mater, and cerebrospinal fluid was
      developed and validated. The von-Mises stress distribution in the cord, the
      longitudinal strain, the cord compression and cross-sectional area at the impact
      center, and the obliteration of the cerebrospinal fluid layer were analyzed for
      three pellet sizes at impact velocities ranging from 1.5m/s to 7.5m/s. The
      results indicate that stress in the cord was substantially elevated when the
      initial impact velocity of the pellet exceeded a threshold of 4.5m/s. Cord
      compression, reduction in cross-sectional area, and obliteration of the
      cerebrospinal fluid increased gradually as the velocity of the pellet increased,
      regardless of the size of the pellet. The present study provides insight into the
      mechanisms underlying spinal cord injury. 

PMID- 24891037
TI  - Should post-mortem brain dissection be performed in Parkinson's disease with
      atypical dementia?
AB  - We describe a patient affected by PD with a rapid progression of cognitive
      decline. This case could suggest the coexistence of many neurodegenerative
      diseases, which is a common condition in older patients. We propose an
      hypothetical trajectory of the cognitive impairment usually associated with motor
      symptoms in the later phase of Parkinsonian patients. The trajectory is almost
      linear in classical Parkinson's disease dementia (PDD), while a constant
      acceleration of the cognitive decline with a subsequent change of the slope of
      the direction could suggest the coexistence of PD with other neurodegenerative
      disease. Finally, if the cognitive decline in PD is comparable to a "stepped"
      decline, vascular lesions could be the cause of the change of the slope. This
      case could suggest to request an autopsy in all cases of unexplained PDD, for
      better understanding the mixture of non-motor symptoms in PD. 

PMID- 24891038
TI  - Thermally induced growth of ZnO nanocrystals on mixed metal oxide surfaces.
AB  - An in situ method for the growth of ZnO nanocrystals on Zn/Al mixed metal oxide
      (MMO) surfaces is presented. The key to this method is the thermal treatment of
      Zn/Al layered double hydroxides (Zn/Al LDHs) in the presence of nitrate anions,
      which results in partial demixing of the LDH/MMO structure and the subsequent
      crystallization of ZnO crystals on the surface of the forming MMO layers. In a
      first experimental series, thermal treatment of Zn/Al LDHs with different
      fractions of nitrate and carbonate in the interlayer space was examined by
      thermogravimetry coupled with mass spectrometry (TG-MS) and in situ XRD. In a
      second experimental series, Zn/Al LDHs with only carbonate in the interlayer
      space were thermally treated in the presence of different amounts of an external
      nitrate source (NH4NO3). All obtained Zn/Al MMO samples were analysed by electron
      microscopy, nitrogen physisorption and powder X-ray diffraction. The gas phase
      formed during nitrate decomposition turned out to be responsible for the
      formation of crystalline ZnO nanoparticles. Accordingly, both interlayer nitrate
      and the presence of ammonium nitrate led to the formation of supported ZnO
      nanocrystals with mean diameters between 100 and 400 nm, and both methods offer
      the possibility to tailor the amount and size of the ZnO crystals by means of the
      amount of nitrate.

PMID- 24891040
TI  - The origins and progress of genomics research on Tef (Eragrostis tef).
AB  - Tef, Eragrostis tef (Zucc.) Trotter, is the most important cereal in Ethiopia.
      Tef is cultivated by more than five million small-scale farmers annually and
      constitutes the staple food for more than half of the population of 80 million.
      The crop is preferred by both farmers and consumers due to its beneficial traits
      associated with its agronomy and utilization. The genetic and phenotypic
      diversity of tef in Ethiopia is a national treasure of potentially global
      importance. In order for this diversity to be effectively conserved and utilized,
      a better understanding at the genomic level is necessary. In the recent years,
      tef has become the subject of genomic research in Ethiopia and abroad. Genomic
      assisted tef improvement holds tremendous potential for improving productivity,
      thereby benefiting the smallholder farmers who have cultivated and relied on the
      crop for thousands of years. It is hoped that such research endeavours will
      provide solutions to some of the age-old problems of tef's husbandry. In this
      review, we provide a brief description of the genesis and progress of tef genomic
      research to date, suggest ways to utilize the genomic tools developed so far,
      discuss the potential of genomics to enable sustainable conservation and use of
      tef genetic diversity and suggest opportunities for the future research. 

PMID- 24891041
TI  - Is it safe to perform joint infiltrations or aspirations in patients
      anticoagulated with acenocoumarol?
AB  - The purpose of this study is to determine the rate of bleeding complications in
      patient's anticoagulated with acenocoumarol according to the international
      normalized ratio (INR) coagulation index. A cross-sectional study was performed
      with 901 charts of patients who underwent arthrocentesis or joint infiltration
      between 2009 and 2013; the charts were grouped on the basis of having an INR
      higher or lower than 2.0 (268 and 633, respectively). Comparisons were performed
      in terms of rates of early or late bleeding complications. A 0.37% rate of early
      bleeding complications (< 24hours) was observed in the group of patients with
      INR<2 and 0.99% in the group of patients with INR>=2 (P=.47). Only one case of
      late complication was presented by bleeding between 24 hours and 30 days, in the
      group of patients with INR>=2. We conclude that oral anticoagulation with
      acenocoumarol at terapeutical doses does not increase the risk of bleeding joint
      punctures.

PMID- 24891042
TI  - A comparison of epidermal growth factor receptor mutation testing methods in
      different tissue types in non-small cell lung cancer.
AB  - The detection of somatic epidermal growth factor receptor (EGFR) mutations is
      valuable when an appropriate therapy, either EGFR-tyrosine kinase inhibitor (TKI)
      therapy or chemotherapy, for patients with advanced non-small cell lung cancer
      (NSCLC) needs to be selected. Although it is well-understood that EGFR mutation
      detection is significant for the decision-making regarding treatment, no
      consensus on the methodology that should be the most preferebale for detecting
      mutations in clinical practice has been reached. The presence of false positives
      due to the technique carried out for mutation analysis affects the accurate
      estimation of response EGFR-TKI therapy. Furthermore, false negatives directly
      exclude the potential application of an EGFR-TKI. In the present study, we
      present the results of detecting EGFR mutations in individual sample types using
      three different low- or high-sensitivity techniques. We suggest that the choice
      of the method used should be made based on the type of the sample. Our results
      revealed that EGFR mutations were less frequently detected in bronchoscopic
      biopsies, regardless of the method used. However, the amplification refractory
      mutation system (ARMS) was optimal owing to the small amount of DNA prepared for
      biopsy. The cytology sample was a valuable alternative to traditional samples,
      given that a sensitive method for detecting mutations was used. For surgical
      resections, the testing method may be selected based on the expertise of each
      laboratory, but direct sequencing is highly recommended. We also suggest that two
      methods should be used sequentially (the screening and targeted methods) in
      clinical practice due to the presence of non-neglected discordance between any
      method from its own benefits and drawbacks.

PMID- 24891044
TI  - Development of new polar monolithic coatings for stir bar sorptive extraction.
AB  - Polar vinyl monomers have been used for the synthesis of several polymer
      monoliths, to serve as novel coatings for stir bar sorptive extraction; the
      monovinyl monomers 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol)
      monomethacrylate) (PEGMA) were copolymerized with (apolar) divinylbenzene (DVB)
      and/or pentaerythritol triacrylate (PETRA), both of which are cross-linking
      agents. After the optimization of the most important synthesis parameters, which
      included the ratio between total monomers and porogen, the nature of the porogen,
      and the monomer ratios, inter alia, three mechanically stable, polar monolithic
      coatings for stir bar sorptive extraction were obtained that were based on
      poly(HEMA-co-DVB), poly(HEMA-co-PETRA), and poly(PEGMA-co-PETRA). Thereafter, and
      in order to evaluate the hydrophilicity of the resulting monoliths, they were
      applied as materials in the stir bar sorptive extraction of a group of emerging
      pollutants with a wide range of polarities. The results showed that both the
      poly(HEMA-co-DVB) and poly(PEGMA-co-PETRA) materials could be used to extract
      both polar and nonpolar compounds by stir bar sorptive extraction, in an
      effective manner. Taking into account the desired chemical and morphological
      properties, as well as the extraction efficiencies, the poly(PEGMA-co-PETRA)
      material seemed to be a particularly promising monolith for application as a
      novel coating in stir bar sorptive extraction. 

PMID- 24891039
TI  - Sustainable harvest: managing plasticity for resilient crops.
AB  - Maintaining crop production to feed a growing world population is a major
      challenge for this period of rapid global climate change. No consistent
      conceptual or experimental framework for crop plants integrates information at
      the levels of genome regulation, metabolism, physiology and response to growing
      environment. An important role for plasticity in plants is assisting in
      homeostasis in response to variable environmental conditions. Here, we outline
      how plant plasticity is facilitated by epigenetic processes that modulate
      chromatin through dynamic changes in DNA methylation, histone variants, small
      RNAs and transposable elements. We present examples of plant plasticity in the
      context of epigenetic regulation of developmental phases and transitions and map
      these onto the key stages of crop establishment, growth, floral initiation,
      pollination, seed set and maturation of harvestable product. In particular, we
      consider how feedback loops of environmental signals and plant nutrition affect
      plant ontogeny. Recent advances in understanding epigenetic processes enable us
      to take a fresh look at the crosstalk between regulatory systems that confer
      plasticity in the context of crop development. We propose that these insights
      into genotype * environment (G * E) interaction should underpin development of
      new crop management strategies, both in terms of information-led agronomy and in
      recognizing the role of epigenetic variation in crop breeding.

PMID- 24891043
TI  - Prospective European survey on atrial fibrillation ablation: clinical
      characteristics of patients and ablation strategies used in different countries.
AB  - BACKGROUND: Atrial fibrillation (AF) ablation is widely adopted. Our aim was to
      conduct a prospective multicenter survey to verify patients' characteristics,
      approaches, and technologies adopted across Europe. METHODS AND RESULTS: A total
      of 35 centers in 12 countries actively participated in the study and 940 patients
      (median age 60 years) were enrolled. AF was paroxysmal, persistent, and long
      lasting persistent in 52.4%, 36%, and 11.6% of patients, respectively; 95.5% of
      patients were symptomatic and 91.4% were refractory to antiarrhythmic therapy.
      Redo procedures were performed in 20.9%. Pulmonary vein isolation (PVI) emerged
      as the cornerstone of ablative therapy and has been performed in 98.7% of
      procedures, with confirmation of PVI in 92.9% of cases. The ablation of
      nonparoxysmal AF was not generally limited to isolating the PVs and several
      adjunctive approaches are adopted, particularly in the case of long-lasting
      persistent AF. Linear lesions or elimination of complex fractionated atrial
      electrograms were more frequently added. Circular mapping catheters and imaging
      techniques were seen to be used in about two-thirds of cases. Radiofrequency
      energy was delivered through open irrigated catheters in 68% of cases.
      CONCLUSIONS: European centers are largely following the recommendations of the
      guidelines and the expert consensus documents for AF ablation. AF ablation is
      mainly performed in relatively young patients with symptomatic drug refractory AF
      and no or minimal heart disease. Patients with paroxysmal AF are the most
      frequently treated with a quite uniform ablative approach across Europe. A less
      standardized approach was observed in nonparoxysmal AF patients.

PMID- 24891045
TI  - How changing root system architecture can help tackle a reduction in soil
      phosphate (P) levels for better plant P acquisition.
AB  - The readily available global rock phosphate (P) reserves may run out within the
      next 50-130 years, causing soils to have a reduced P concentration which will
      affect plant P uptake. Using a combination of mathematical modelling and
      experimental data, we investigated potential plant-based options for optimizing
      crop P uptake in reduced soil P environments. By varying the P concentration
      within a well-mixed agricultural soil, for high and low P (35.5-12.5 mg L(-1)
      respectively using Olsen's P index), we investigated branching distributions
      within a wheat root system that maximize P uptake. Changing the root branching
      distribution from linear (evenly spaced branches) to strongly exponential (a
      greater number of branches at the top of the soil) improves P uptake by 142% for
      low-P soils when root mass is kept constant between simulations. This causes the
      roots to emerge earlier and mimics topsoil foraging. Manipulating root branching
      patterns, to maximize P uptake, is not enough on its own to overcome the drop in
      soil P from high to low P. Further mechanisms have to be considered to fully
      understand the impact of P reduction on plant development. 

PMID- 24891046
TI  - Brain MRI abnormalities and spectrum of neurological and clinical findings in
      three patients with proximal 16p11.2 microduplication.
AB  - The phenotype of recurrent ~600 kb microdeletion and microduplication on proximal
      16p11.2 is characterized by a spectrum of neurodevelopmental impairments
      including developmental delay and intellectual disability, epilepsy, autism and
      psychiatric disorders which are all subject to incomplete penetrance and variable
      expressivity. A variety of brain MRI abnormalities were reported in patients with
      16p11.2 rearrangements, but no systematic correlation has been studied among
      patients with similar brain anomalies, their neurodevelopmental and clinical
      phenotypes. We present three patients with the proximal 16p11.2 microduplication
      exhibiting significant developmental delay, anxiety disorder and other variable
      clinical features. Our patients have abnormal brain MRI findings of cerebral T2
      hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or
      neurological findings in two cases prompted an extensive diagnostic work-up. One
      patient has exhibited neurological regression and progressive vision impairment
      and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the
      clinical course and phenotype of these patients in regard to the clinical
      significance of the cerebral lesions and the need for MRI surveillance. We
      conclude that in all three patients the lesions were not progressive, did not
      show any sign of malignant transformation and could not be correlated to specific
      clinical features. We discuss potential etiologic mechanisms that may include
      overexpression of genes within the duplicated region involved in control of cell
      proliferation and complex molecular mechanisms such as the MAPK/ERK pathway.
      Systematic studies in larger cohorts are needed to confirm our observation and to
      establish the prevalence and clinical significance of these neuroanatomical
      abnormalities in patients with 16p11.2 duplications.

PMID- 24891047
TI  - Help or hindrance: young people's experiences of predictive testing for
      Huntington's disease.
AB  - A growing number of young people (YP) are requesting predictive testing (PT) for
      Huntington's disease (HD), yet there is little research in this area. The aim of
      this study was to explore YP's experiences of PT for HD, the impact of their
      result and any gaps in information or support. In-depth interviews were conducted
      with YP who sought PT for HD from nationally funded Genetics Services.
      Participants were recruited through the Grampian Genetics Service or Scottish
      Huntington's Association. Twelve female participants aged 17-26 years were
      recruited (seven below 20 years). Pre- and post-test interviews were conducted
      where possible. A qualitative thematic analysis suggests three main testing
      experiences, regardless of test result. Testing may be: (i) a journey of
      empowerment, (ii) an ambivalent process or (iii) a poor experience. In pre-test
      counselling, gaps in emotional support were highlighted. The post-test period was
      particularly difficult if there were unanticipated changes in family dynamics or
      an individual's result contradicted what they expected 'deep down'. YP's
      experiences of PT for HD are generally similar to those of adults, but testing
      may help or interfere with key issues related to this age and stage. Implications
      for clinical practice are outlined. 

PMID- 24891048
TI  - Therapeutic plasma exchange rapidly improves cardiac allograft function in
      patients with presumed antibody-mediated rejection.
AB  - BACKGROUND: Allograft dysfunction due to presumed antibody-mediated rejection
      (pAMR) is one of the most serious complications of heart transplantation.
      Combination therapies of high-dose steroids, intravenous immune globulin, and/or
      therapeutic plasma exchange (TPE) are often used in this setting. METHODS: We
      performed a 9-year retrospective review of all episodes of pAMR treated with TPE
      at our institution. pAMR diagnosis was based on clinical and pathologic findings.
      Left ventricular ejection fraction (LVEF) was measured at baseline, prior to
      initiation of TPE, and during the course of treatment. RESULTS: There were 42
      patients with 47 episodes of pAMR treated with TPE. The majority of episodes were
      treated with three TPE; however, eight required only two TPE and five episodes
      required >3 TPE. All episodes of pAMR had LVEF measured before and after the
      series of TPEs. The mean pre-TPE LVEF was 38% compared with a post-therapy mean
      LVEF of 50% (P < 0.0001). In 16 episodes of pAMR, for which LVEF was measured
      following each apheresis, there was significant improvement of allograft function
      after the first TPE (pre-TPE mean LVEF of 31% and post-first TPE mean LVEF of
      37%; P = 0.02). Incremental and significant improvement in allograft function
      continued following each TPE. Changes in human leukocyte antigen-donor specific
      antibodies and fibrinogen did not correlate with ejection fraction response.
      CONCLUSIONS: The rapid improvement in allograft function in our patients is most
      likely due to TPE as other pharmacologic interventions have longer onset. TPE
      should be considered a first-line intervention in the setting of pAMR.

PMID- 24891049
TI  - Introduction to photobiology.
AB  - Photobiology is the study of the local and systemic effects of incident radiation
      on living organisms. Solar radiation is made up of ultraviolet, visible and
      infrared radiation. Ultraviolet radiation is made up of UV-C, UV-B, and UV-A. Sun
      exposure can lead to sunburn, tanning, vitamin D production, photoaging, and
      carcinogenesis. Phototherapy is the use of nonionizing radiation to treat
      cutaneous disease. Various types of artificial light sources are used for photo
      testing and phototherapy. 

PMID- 24891050
TI  - Evaluation of patients with photodermatoses.
AB  - The systematic evaluation of photosensitive patients involves a comprehensive
      history, physical examination, phototesting, and, if necessary, photopatch
      testing and laboratory evaluation. Polymorphous light eruption, chronic actinic
      dermatitis, solar urticaria, and photosensitivity secondary to systemic
      medications are the most commonly encountered photodermatoses in dermatology
      clinics worldwide. 

PMID- 24891052
TI  - Photoaging.
AB  - This article discusses photoaging or premature skin aging from chronic
      ultraviolet exposure. This is an important cosmetic concern for many dermatologic
      patients. Clinical signs include rhytids, lentigines, mottled hyperpigmentation,
      loss of translucency, and decreased elasticity. These changes are more severe in
      individuals with fair skin and are further influenced by individual ethnicity and
      genetics. Photoaging may be prevented and treated with a variety of modalities,
      including topical retinoids, cosmeceuticals, chemical peels, injectable
      neuromodulators, soft tissue fillers, and light sources. 

PMID- 24891053
TI  - Photocarcinogenesis: an epidemiologic perspective on ultraviolet light and skin
      cancer.
AB  - Photocarcinogenesis is the result of a complex interplay between ultraviolet
      radiation, DNA damage, mutation formation, DNA repair, apoptosis, and the immune
      system. Recent trends show an increase in incidence of both melanoma and
      nonmelanoma skin cancers. Some individuals have a genetic predisposition toward
      increased risk for skin cancer, whereas others experience increased risk through
      ultraviolet exposure and subsequent mutation formation. The initiation and
      propagation pathways of melanoma and nonmelanoma skin cancers differ but have
      some elements in common. The increase in incidence of skin cancer has been
      discovered to vary among age groups and gender. 

PMID- 24891054
TI  - Polymorphous light eruption: clinic aspects and pathogenesis.
AB  - Polymorphous light eruption is an immunologically mediated photodermatosis with
      high prevalence, particularly among young women in temperate climates,
      characterized by pruritic skin lesions of variable morphology, occurring in
      spring or early summer on sun-exposed body sites. A resistance to ultraviolet
      radiation (UVR)-induced immunosuppression and a subsequent delayed-type
      hypersensitivity response to a photoantigen have been suggested as key factors in
      the disease. Molecular and immunologic disturbances associated with disease
      pathogenesis include a failure of skin infiltration by neutrophils and other
      regulatory immune cells on UVR exposure linked to a disturbed cytokine
      microenvironment. Standard management is based on prevention. 

PMID- 24891055
TI  - Actinic prurigo.
AB  - Actinic prurigo is a chronic photodermatosis with onset in childhood or before 20
      years of age. It is most prevalent in Amerindians and Latin American mestizos,
      although it has been reported worldwide. Patients present with photodistributed,
      erythematous excoriated papules, cheilitis, and conjunctivitis. There is strong
      association with human leukocyte antigen DR4, especially the DRB1*0407 subtype.
      Treatment consists of photoprotection and the use of thalidomide. 

PMID- 24891051
TI  - Photoimmunology.
AB  - The discipline that investigates the biologic effects of ultraviolet radiation on
      the immune system is called photoimmunology. Photoimmunology evolved from an
      interest in understanding the role of the immune system in skin cancer
      development and why immunosuppressed organ transplant recipients are at a greatly
      increased risk for cutaneous neoplasms. In addition to contributing to an
      understanding of the pathogenesis of nonmelanoma skin cancer, the knowledge
      acquired about the immunologic effects of ultraviolet radiation exposure has
      provided an understanding of its role in the pathogenesis of other
      photodermatologic diseases. 

PMID- 24891056
TI  - Hydroa vacciniforme and solar urticaria.
AB  - Hydroa vacciniforme (HV) and solar urticaria (SU) are uncommon immunologically
      mediated photodermatoses. HV occurs almost exclusively in children, usually
      beginning in childhood and remitting spontaneously by adolescence. Association
      with chronic Epstein-Barr virus infection has been reported in HV, which raises
      the possibility of lymphoproliferative disorders in these patients. SU is
      characterized by skin erythema, swelling, and whealing immediately after sun
      exposure. Although several treatment options are available, the management of
      both conditions remains a challenge. 

PMID- 24891057
TI  - Chronic actinic dermatitis.
AB  - Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis
      characterized by pruritic eczematous and lichenified plaques located
      predominantly on sun-exposed areas with notable sparing of eyelids, skin folds,
      and postauricular skin. CAD is thought to be due to secondary photosensitization
      of an endogenous antigen in the skin. Management of CAD should include strict
      photoprotection and topical agents, including corticosteroids and calcineurin
      inhibitors. Other treatments with noted efficacy include oral prednisone,
      cyclosporine, azathioprine, and mycophenolate mofetil. Photoprotection and
      avoidance of allergens, if identified, may lead to spontaneous resolution of CAD
      in 50% of patients over 15 years. 

PMID- 24891058
TI  - Drug-induced photosensitivity.
AB  - Drug-induced photosensitivity is common. The principal mechanism of systemic drug
      photosensitivity is phototoxicity and the principal mechanism of topical drug
      photosensitivity is photoallergy. Photopatch testing is helpful to determine
      suspected topical agent photoallergies (eg, from ultraviolet filters in
      sunscreens) but generally not helpful in detecting systemic drug
      photosensitivity. Drug-induced photosensitivity is usually best managed by
      stopping the suspected drug. Other measures, including phototherapy using
      wavelengths that do not elicit the response, are sometimes necessary. 

PMID- 24891059
TI  - The cutaneous porphyrias.
AB  - The porphyrias are a group of mainly inherited disorders of heme biosynthesis
      where accumulation of porphyrins and/or porphyrin precursors gives rise to 2
      types of clinical presentation: cutaneous photosensitivity and/or acute
      neurovisceral attacks. The cutaneous porphyrias present with either bullous skin
      fragility or nonbullous acute photosensitivity. This review discusses the
      epidemiology, pathogenesis, clinical presentation, laboratory diagnosis,
      complications, and current approach to porphyria management. Although focusing
      mainly on their dermatological aspects, the article also covers the management of
      acute porphyria, which by virtue of its association with variegate porphyria and
      hereditary coproporphyria, may become the responsibility of the clinical
      dermatologist. 

PMID- 24891060
TI  - Photoaggravated disorders.
AB  - Photoaggravated skin disorders are diseases that occur without UV radiation but
      are sometimes or frequently exacerbated by UV radiation. In conditions, such as
      lupus erythematosus, photoaggravation occurs in a majority of patients, whereas
      in conditions, such as psoriasis and atopic dermatitis, only a subset of patients
      demonstrate photoaggravation. Polymorphous light eruption is a common
      photodermatosis in all skin types, making it important to differentiate
      photoaggravation of an underlying disorder, such as lupus erythematosus, from
      superimposed polymorphous light eruption. Disease-specific treatments should be
      instituted where possible. A key component of management of photoaggravated
      conditions is photoprotection with behavioral change, UV-protective clothing, and
      broad-spectrum sunscreen. 

PMID- 24891061
TI  - UV-based therapy.
AB  - UV phototherapy has a long history of use for the treatment of select diseases in
      dermatology. Its use has evolved into more effective and targeted modalities,
      including psoralen + UV-A photochemotherapy, narrowband UV-B, excimer laser, and
      UV-A1 phototherapy. With its proven record of efficacy and safety, UV
      phototherapy is an excellent option in the treatment of an ever-growing number of
      skin conditions. 

PMID- 24891062
TI  - Photodynamic therapy.
AB  - Photodynamic therapy (PDT) relies on the interaction between a photosensitizer,
      the appropriate wavelength, and oxygen to cause cell death. First introduced
      about 100 years ago, PDT has continued to evolve in dermatology into a safe and
      effective treatment option for several dermatologic conditions. PDT is also used
      by pulmonologists, urologists, and ophthalmologists. This article focuses on the
      history of PDT, mechanism of action, photosensitizers and light sources used,
      therapeutic applications and expected dermatologic outcomes, as well as
      management of adverse events. 

PMID- 24891063
TI  - Sunscreens: a review of health benefits, regulations, and controversies.
AB  - Ultraviolet radiation plays a major role in the development of nonmelanoma and
      melanoma skin cancers. Photoprotection by sunscreens has been shown to prevent
      the development of actinic keratosis, squamous cell carcinoma, melanoma, and
      photoaging. However, these benefits are only derived if the users apply sunscreen
      appropriately and practice other sun protection measures. This review discusses
      the health benefits provided by sunscreen use, updates the latest regulatory
      landscape on sunscreen, and addresses the controversies and limitations
      associated with sunscreen use. 

PMID- 24891064
TI  - Photoprotection: clothing and glass.
AB  - Ultraviolet (UV) radiation (UVR) has well-known adverse effects on the skin and
      eyes. Little attention is given to physical means of photoprotection, namely
      glass, window films, sunglasses, and clothing. In general, all types of glass
      block UV-B. For UV-A, the degree of transmission depends on the type, thickness,
      and color of the glass. Adding window films to glass can greatly decrease the
      transmission of UV-A. Factors that can affect the transmission of UVR through
      cloth include tightness of weave, thickness, weight, type of fabrics, laundering,
      hydration, stretch, fabric processing, UV absorbers, color, and fabric-to-skin
      distance. 

PMID- 24891065
TI  - Photodermatology.

PMID- 24891066
TI  - Scapholunate advanced collapse: a pictorial review.
AB  - Scapholunate advanced collapse (SLAC) is the most common cause of osteoarthritis
      involving the wrist. Along with clinical investigation, radiological studies play
      a vital role in the diagnosis of SLAC wrist. Given that the osteoarthritic
      changes that are seen with SLAC occur in a predictable progressive pattern, it is
      important to understand the pathological evolution of SLAC to be able to
      recognise the associated progressive imaging findings seen with this disease
      process. Focusing on radiological findings, this article provides a pictorial
      review of the anatomy of the scapholunate interosseous ligament as well as the
      common terminology and biomechanical alterations seen in the pathway leading to
      the development of SLAC arthropathy. We will then discuss two additional common
      causes of SLAC wrist and their imaging findings, namely scaphoid non-union
      advanced collapse and calcium pyrophosphate dehydrate disease. In addition, we
      will provide a brief overview of the current treatment options of these
      pathological entities. TEACHING POINTS: * SLAC is the most common cause of
      osteoarthritis involving the wrist. * Arthritic changes of SLAC occur in a
      predictable progressive pathological and radiographic pattern. * Imaging is key
      for diagnosing, monitoring progression and assessing post-treatment changes of
      SLAC.

PMID- 24891067
TI  - Prucalopride decreases esophageal acid exposure and accelerates gastric emptying
      in healthy subjects.
AB  - BACKGROUND: The 5-HT4 receptor agonist prucalopride is a prokinetic drug which
      improves colonic motility. Animal data and in vitro studies suggest that
      prucalopride also affects gastric and esophageal motor function. We aimed to
      assess the effect of prucalopride on gastric emptying, esophageal motility, and
      gastro-esophageal reflux in man. METHODS: In this double-blind, placebo
      controlled, randomized, crossover study, we included 21 healthy volunteers who
      received 4 mg prucalopride or placebo per day for 6 days. We performed high
      resolution manometry (HRM) followed by 120-min HRM-pH-impedance monitoring after
      a standardized meal, ambulatory 24-h pH-impedance monitoring, and gastric
      emptying for solids. KEY RESULTS: Prucalopride decreased (median [IQR]) total
      acid exposure time (3.4 [2.5-5.6] vs 1.7 [0.8-3.5] %, p < 0.05). The total number
      of reflux events was unaffected by prucalopride, however, the number of reflux
      events extending to the proximal esophagus was reduced by prucalopride (15.5 [9.8
      25.5] vs 10.5 [5.3-17.5], p < 0.05). Furthermore, prucalopride improved acid
      clearance time (77.5 [47.8-108.8] vs 44.0 [30.0-67.8] s, p < 0.05). Prucalopride
      did not affect the number of transient lower esophageal sphincter (LES)
      relaxations or their association with reflux events. Esophageal motility and
      basal pressure of the LES were not affected by prucalopride. Prucalopride
      increased gastric emptying (T1/2 ; 32.7 [27.9-44.6] vs 49.8 [37.7-55.0] min, p <
      0.05) and decreased residue after 120 min (8.8 [4.4-14.8] vs 2.7 [1.3-5.4] %, p <
      0.05). CONCLUSIONS & INFERENCES: Prucalopride reduces esophageal acid exposure
      and accelerates gastric emptying in healthy male volunteers. These findings
      suggest that the drug could be effective for treatment of patients with reflux
      disease and functional dyspepsia.

PMID- 24891068
TI  - Pigments through time.

PMID- 24891069
TI  - Catalytic ethanolysis of Kraft lignin into high-value small-molecular chemicals
      over a nanostructured alpha-molybdenum carbide catalyst.
AB  - We report the complete ethanolysis of Kraft lignin over an alpha-MoC1-x /AC
      catalyst in pure ethanol at 280  degrees C to give high-value chemicals of low
      molecular weight with a maximum overall yield of the 25 most abundant liquid
      products (LP25) of 1.64 g per gram of lignin. The LP25 products consisted of C6 
      C10 esters, alcohols, arenes, phenols, and benzyl alcohols with an overall
      heating value of 36.5 MJ kg(-1) . C6 alcohols and C8 esters predominated and
      accounted for 82 wt % of the LP25 products. No oligomers or char were formed in
      the process. With our catalyst, ethanol is the only effective solvent for the
      reaction. Supercritical ethanol on its own degrades Kraft lignin into a mixture
      of small molecules and molecular fragments of intermediate size with molecular
      weights in the range 700-1400, differing in steps of 58 units, which is the
      weight of the branched-chain linkage C3 H6 O in lignin. Hydrogen was found to
      have a negative effect on the formation of the low-molecular-weight products. 

PMID- 24891071
TI  - Spatiotemporal variation of groundwater quality using integrated multivariate
      statistical and geostatistical approaches in Amol-Babol Plain, Iran.
AB  - In recent years, groundwater quality has become a global concern due to its
      effect on human life and natural ecosystems. To assess the groundwater quality in
      the Amol-Babol Plain, a total of 308 water samples were collected during wet and
      dry seasons in 2009. The samples were analysed for their physico-chemical and
      biological constituents. Multivariate statistical analysis and geostatistical
      techniques were applied to assess the spatial and temporal variabilities of
      groundwater quality and to identify the main factors and sources of
      contamination. Principal component analysis (PCA) revealed that seven factors
      explained around 75% of the total variance, which highlighted salinity, hardness
      and biological pollution as the dominant factors affecting the groundwater
      quality in the Plain. Two-way analysis of variance (ANOVA) was conducted on the
      dataset to evaluate the spatio-temporal variation. The results showed that there
      were no significant temporal variations between the two seasons, which explained
      the similarity between six component factors in dry and wet seasons based on the
      PCA results. There are also significant spatial differences (p > 0.05) of the
      parameters under study, including salinity, potassium, sulphate and dissolved
      oxygen in the plain. The least significant difference (LSD) test revealed that
      groundwater salinity in the eastern region is significantly different to the
      central and western side of the study area. Finally, multivariate analysis and
      geostatistical techniques were combined as an effective method for demonstrating
      the spatial structure of multivariate spatial data. It was concluded that
      multiple natural processes and anthropogenic activities were the main sources of
      groundwater salinization, hardness and microbiological contamination of the study
      area.

PMID- 24891070
TI  - Effects of new mutations on fitness: insights from models and data.
AB  - The rates and properties of new mutations affecting fitness have implications for
      a number of outstanding questions in evolutionary biology. Obtaining estimates of
      mutation rates and effects has historically been challenging, and little theory
      has been available for predicting the distribution of fitness effects (DFE);
      however, there have been recent advances on both fronts. Extreme-value theory
      predicts the DFE of beneficial mutations in well-adapted populations, while
      phenotypic fitness landscape models make predictions for the DFE of all mutations
      as a function of the initial level of adaptation and the strength of stabilizing
      selection on traits underlying fitness. Direct experimental evidence confirms
      predictions on the DFE of beneficial mutations and favors distributions that are
      roughly exponential but bounded on the right. A growing number of studies infer
      the DFE using genomic patterns of polymorphism and divergence, recovering a wide
      range of DFE. Future work should be aimed at identifying factors driving the
      observed variation in the DFE. We emphasize the need for further theory
      explicitly incorporating the effects of partial pleiotropy and heterogeneity in
      the environment on the expected DFE. 

PMID- 24891072
TI  - Metabolic degradation of imidacloprid in paddy field soil.
AB  - The metabolic degradation and persistence of imidacloprid in paddy field soil
      were investigated following two applications of imidacloprid at 20 and 80 g a.i.
      ha(-1) at an interval of 10 days. The soil samples were collected at various time
      intervals. The limit of quantification for the analysis of imidacloprid and its
      metabolites was obtained at the concentration of 0.01 mg kg(-1). The initial
      deposits of total imidacloprid were found to be 0.44 and 1.61 mg kg(-1) following
      second applications. These residues could not be detected after 60 and 90 days
      following second applications of imidacloprid at lower and higher dosages,
      respectively. In soil, urea metabolite was found to be the maximum, followed by
      olefine, nitrosimine, 6-chloronicotinic acid, 5-hydroxy and nitroguanidine. The
      half-life values (t1/2) of imidacloprid were worked out to be 12.04 and 11.14
      days, respectively, when applied at lower and higher doses, respectively.

PMID- 24891073
TI  - Dynamics of aeolian desertification and its driving forces in the Horqin Sandy
      Land, Northern China.
AB  - Aeolian desertification is one of the most serious environmental and
      socioeconomic problems in arid, semi-arid, and dry subhumid zones. Understanding
      desertification processes and causes is important to provide reasonable and
      effective control measures for preventing desertification. With satellite remote
      sensing images as data source to assess the temporal and spatial dynamics of
      desertification from 1975 to 2010 in the Horqin Sandy Land, dynamic changes of
      aeolian desertification were detected using the human-machine interactive
      interpretation method. The driving factors of local desertification were analyzed
      based on natural and socioeconomic data. The results show that aeolian
      desertified land in the study area covered 30,199 km(2) in 2010, accounting for
      24.1% of the study area. The total area of aeolian desertified land obviously
      expanded from 30,884 km(2) in 1975 to 32,071 km(2) in 1990, and gradually
      decreased to 30,199 km(2) in 2010; aeolian desertified land represented an
      increasing trend firstly and then decreased. During the past 35 years, the
      gravity centers of desertified lands that are classified as extremely severe and
      severe generally migrated to the northeast, whereas those that are moderate and
      slight migrated to the northwest. The migration distance of severely desertified
      land was the largest, which indicated the southern desertified lands were
      improved during the last few decades. In addition, the climatic variation in the
      past 35 years has been favorable to desertification in the Horqin Sandy Land.
      Aeolian desertified land rapidly expanded from 1975 to 1990 under the combined
      effects of climate changes and unreasonable human activities. After the 1990s,
      the main driving factors responsible for the decrease in desertification were
      positive human activities, such as the series of antidesertification and
      ecological restoration projects.

PMID- 24891075
TI  - Sex hormones and the risk of type 2 diabetes mellitus: A 9-year follow up among
      elderly men in Finland.
AB  - AIM: To analyze whether sex hormone levels predict the incidence of type2
      diabetes among elderly Finnish men. METHODS: This was a prospective population
      based study, with a 9-year follow up period. The study population in the
      municipality of Lieto, Finland, consisted of elderly (age >=64 years) men free of
      type 2 diabetes at baseline in 1998-1999 (n = 430). Body mass index and
      cardiovascular disease-adjusted hazard ratios and their 95% confidence intervals
      for type 2 diabetes predicted by testosterone, free testosterone, sex hormone
      binding globulin, luteinizing hormone, and testosterone/luteinizing hormone were
      estimated. RESULTS: A total of 30 new cases of type 2 diabetes developed during
      the follow-up period. After adjustment, only higher levels of testosterone
      (hazard ratio for one-unit increase 0.93, 95% confidence interval 0.87-0.99, P =
      0.020) and free testosterone (hazard ratio for 10-unit increase 0.96, 95%
      confidence interval 0.91-1.00, P = 0.044) were associated with a lower risk of
      incident type 2 diabetes during the follow up. These associations (0.94, 95%
      confidence interval 0.87-1.00, P = 0.050 and 0.95, 95% confidence interval 0.90
      1.00, P = 0.035, respectively) persisted even after additional adjustment of sex
      hormone-binding globulin. CONCLUSION: Higher levels of testosterone and free
      testosterone independently predicted a reduced risk of type 2 diabetes in the
      elderly men.

PMID- 24891076
TI  - Polysomnography reveals nystagmus from benign paroxysmal positional vertigo.

PMID- 24891074
TI  - Protective role of CYP2E1 inhibitor diallyl disulfide (DADS) on alcohol-induced
      malondialdehyde-deoxyguanosine (M1dG) adduct formation.
AB  - BACKGROUND: Alcohol use disorders are often associated with lung disease. Alcohol
      exposure leads to the production of reactive oxygen species, lipid peroxidation,
      and formation of malondialdehyde (MDA) as well as to induce the expression of
      cytochrome p450 2E1 (CYP2E1). Likewise, cigarette smoking can lead to lung lipid
      peroxidation and formation of MDA. MDA can bind to DNA forming MDA-deoxyguanosine
      (M1dG) adducts, which have been implicated in alcohol-related cancers and
      cardiovascular disease. Because CYP2E1 regulates MDA production, and our previous
      studies have shown that alcohol and cigarette smoke can lead to MDA formation, we
      hypothesized that CYP2E1 would modulate M1dG adduct formation and single-strand
      DNA damage in alcohol- and cigarette smoke-exposed lung cells and tissue.
      METHODS: Normal human bronchial epithelial cells (HBECs) were pretreated with 10
      MUM diallyl disulfide (DADS) for 1 hour and treated with 80 mM ethanol (EtOH) +/-
      5% cigarette smoke extract (CSE) for 3 hours for comet assay and 6 hours for
      CYP2E1, MDA, and M1dG adduct assays. C57BL/6 mice were administered 20% EtOH ad
      libitum in drinking water for 8 weeks and exposed to whole-body cigarette smoke
      for 5 weeks. Mice were also fed a CYP2E1 inhibitor, DADS, at 1 MUM/g of feed in
      their daily diet for 7 weeks. Whole lung tissue homogenate was used for CYP2E1,
      MDA, and M1dG adduct assays. RESULTS: EtOH exposure significantly increased HBEC
      olive tail moment. DADS pretreatment of HBECs attenuated this EtOH effect. EtOH
      also induced MDA and M1dG adduct formation, which was also significantly reduced
      by DADS treatment. CSE +/- EtOH did not enhance these effects. In lung tissue
      homogenate of 8-week alcohol-fed mice, MDA and M1dG adduct levels were
      significantly elevated in comparison with control mice and mice fed DADS while
      consuming alcohol. No increase in MDA and M1dG adduct formation was observed in 5
      week cigarette smoke-exposed mice. CONCLUSIONS: These findings suggest that
      CYP2E1 plays a pivotal role in alcohol-induced M1dG adducts, and the use of DADS
      as dietary supplement can reverse the effects of alcohol on M1dG formation.

PMID- 24891077
TI  - Time structure of leg movement activity during sleep in untreated Parkinson
      disease and effects of dopaminergic treatment.
AB  - OBJECTIVES: To evaluate the specific time structure of periodic leg movements
      during sleep (PLMS) in untreated Parkinson disease (PD) patients by means of an
      advanced analysis; and to evaluate the effects of treatment on this activity, in
      a cross-sectional comparison and in a prospective follow-up study, in a subgroup
      of previously untreated patients. METHODS: Forty-four consecutive PD patients
      were enrolled in the study; 19 had not yet started any drug therapy for PD
      (PDnother); 10 out of these patients were re-evaluated after an average time lag
      of 19.6months from baseline. The remaining 25 patients (PDther) were taking l
      dopa and/or dopamine agonists. Eighteen age-matched normal controls were also
      included. All subjects underwent a polysomnographic recording and the time
      structure of their sleep leg movement activity was analyzed by means of the
      periodicity index and other advanced measures. RESULTS: Both PD groups tended to
      show increased PLMS and decreased isolated limb movement activity with respect to
      controls. PLMS index >15/h was found in 26.3% of PDnother patients, 24.0% of
      PDther subjects, and in 16.7% of controls; none of the three PDnother patients
      who had PLMS index >15/h at baseline sustained this level at follow-up, nor did
      the other seven patients. The intermovement interval distribution showed a clear
      peak at 10-40s in the PDnother group; a suppression of this peak was observed
      after the introduction of dopaminergic treatment in the subgroup of 10 PDnother
      patients. Both groups of PD patients showed a progressively decreasing number of
      PLMS through the night; an almost complete abolition of PLMS was seen in the
      first 2h of sleep after the introduction of dopaminergic drug therapy.
      CONCLUSION: Our data do not seem to support the hypothesis that PLMS are
      particularly frequent in PD but seem to indicate an interaction between PD
      pathophysiology and genetic predisposition for PLMS, producing a slightly
      increased number of patients with this sleep motor phenomenon when compared to
      controls.

PMID- 24891078
TI  - Working memory deficit in patients with restless legs syndrome: an event-related
      potential study.
AB  - OBJECTIVE: The aim of this study was to investigate whether there is a working
      memory (WM) deficit in restless legs syndrome (RLS) patients, by studying the
      Sternberg WM task of event-related potential (ERP). METHODS: Thirteen drug-naive
      RLS patients and 13 healthy age-matched controls with no sleep disturbances
      participated in the present study. P300 ERP was recorded during Sternberg WM task
      using digits as mnemonic items. P300 amplitudes and reaction times were compared
      between groups (RLS vs. control) considering brain regions (frontal, central, and
      parietal) and memory load sizes (two, three, and four) as within-subject factors.
      Clinical and sleep-related variables were correlated with P300 amplitude.
      RESULTS: The reaction time in RLS patients was significantly longer than controls
      over all memory load sizes. The P300 amplitude at parietal regions in RLS
      patients was significantly lower than in controls regardless of memory load
      sizes, which was significantly negatively correlated with duration of RLS history
      in RLS patients. CONCLUSION: Our study suggests that patients with severe RLS
      have WM deficits. Furthermore, negative correlation of P300 amplitudes with the
      duration of RLS illness suggests that cerebral cortical dysfunction in RLS
      patients results from repeated RLS symptom attacks.

PMID- 24891079
TI  - Evaluation of five different questionnaires for assessing sleep apnea syndrome in
      a sleep clinic.
AB  - BACKGROUND: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a major cause of
      morbidity and mortality. Different clinical models and questionnaires have been
      used to evaluate patients with the highest OSAHS probability. OBJECTIVES: To
      evaluate the clinical utility of five different questionnaires--STOP, STOPBang
      (SB), Berlin Questionnaire (BQ), Epworth Sleepiness Scale (ESS), and 4-Variable
      Screening Tool (4-V) - in a sleep clinic in order to identify patients at risk
      for OSAHS and to assess the best possible combination of these tools. METHODS:
      1853 (74.4% males) patients (mean age 52+/-14 years; mean body mass index 32.8+/
      7 kg/m2) visiting a sleep clinic were studied retrospectively. RESULTS: SB had
      the highest sensitivity (97.6%), the largest area under the receiver operating
      characteristics curve (AUC) (0.73; 95% CI, 0.7-0.76) and best OR (5.9; 95% CI,
      3.6-9.5), but the lowest specificity (12.7%) for AHI > or =15. The 4-V > or = 14
      had the highest specificity (74.4%) followed by ESS (67%). BQ had good
      sensitivity (87%), worse specificity (33%) than 4-V and ESS but better than STOP
      (13%) and SB (12.7%). The combination of questionnaires did not improve their
      predictive value. CONCLUSIONS: SB had the highest sensitivity, OR, and AUC, but
      rather low specificity, and 4-V the highest specificity. The combination of
      different questionnaires did not improve their predictive value.

PMID- 24891080
TI  - Sleep apnea increased incidence of primary central nervous system cancers: a
      nationwide cohort study.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) was associated with increased
      incidence of all cancers. We aimed to determine the risk for primary central
      nervous system (CNS) cancers in patients with sleep apnea syndrome. METHODS: A
      total of 23,055 incident cases of newly diagnosed sleep apnea syndrome (sleep
      apnea group) were identified between 2000 and 2003 in the medical claims database
      of Taiwan's National Health Institute (NHI) program and were matched by age and
      gender to patients without OSA (comparison group) in the same period. The
      occurrence of primary malignant CNS cancers was measured 2 years after the index
      date over a 10-year period. RESULTS: The incidence density of primary CNS cancers
      (per 10,000 individual-years) was 2.14 and 1.28, respectively, for the OSA and
      comparison groups. The overall risk for developing primary CNS cancers was
      significantly higher in the OSA group (adjusted hazard ratio [HR], 1.54; P=0.046)
      after adjusting for age, gender, and obesity, among other variables. Subgroup
      analysis revealed a significantly higher risk for primary brain cancers but not
      primary spinal cord cancers in the OSA subgroup (adjusted HR, 1.71; P=0.027). The
      analysis also revealed a significantly higher risk for primary CNS cancers in the
      insomnia with OSA subgroup (adjusted HR, 2.20; P=0.001) and in the OSA without
      surgical treatment subgroup (adjusted HR, 1.831; P=0.003). CONCLUSIONS: OSA,
      especially with insomnia, may increase the risk for primary CNS cancer
      development, though surgical treatment may reduce this risk in participants with
      OSA.

PMID- 24891081
TI  - Effects of one night of induced night-wakings versus sleep restriction on
      sustained attention and mood: a pilot study.
AB  - OBJECTIVE: Despite their high prevalence in daily life, repeated night-wakings
      and their cognitive and emotional consequences have received less research
      attention compared to other types of sleep disturbances. Our aim was to
      experimentally compare the effects of one night of induced infrequent night
      wakings (of ~15 min, each requiring a purposeful response) and sleep restriction
      on sustained attention and mood in young adults. METHODS: In a within-between
      subjects counterbalanced design, 61 healthy adults (40 females; aged 20-29 years)
      underwent home assessments of sustained attention and self-reported mood at two
      times: after a normal (control) sleep night, and after a night of either sleep
      restriction (4h in bed) or induced night-wakings (four prolonged awakenings
      across 8h in bed). Sleep was monitored using actigraphy and sleep diaries.
      Sustained attention was assessed using an online continuous performance test
      (OCPT), and mood was reported online using the Profile of Mood States (POMS).
      RESULTS: Actigraphic data revealed good compliance with experimental sleep
      requirements. Induced night-wakings and sleep restriction both resulted in more
      OCPT omission and commission errors, and in increased depression, fatigue and
      confusion levels and reduced vigor compared to the normal sleep night. Moreover,
      there were no significant differences between the consequences of induced
      awakenings and sleep restriction. CONCLUSIONS: Our pilot study indicates that,
      similar to sleep restriction, one night of life-like repeated night-wakings
      negatively affects mood and sustained attention.

PMID- 24891083
TI  - Reflectance confocal microscopy as a second-level examination in skin oncology
      improves diagnostic accuracy and saves unnecessary excisions: a longitudinal
      prospective study.
AB  - BACKGROUND: Dermatoscopy increases both the sensitivity and specificity of
      melanoma diagnosis. Reflectance confocal microscopy (RCM) is a noninvasive
      technique that complements dermatoscopy in the evaluation of equivocal lesions at
      cellular resolution. OBJECTIVES: To determine prospectively the potential impact
      of confocal microscopy when implemented in a routine melanoma diagnosis workflow.
      METHODS: Patients referred to a single melanoma clinic were consecutively
      enrolled. At dermatoscopy, patients were referred to one of the following
      pathways: (i) no further examination or (ii) RCM examination. On examination
      atypical lesion(s) were referred for either (a) RCM documentation (lesions with
      consistent suspicious clinical/dermatoscopic criteria, already qualified and
      scheduled for surgical excision) or (b) RCM consultation for equivocal lesions,
      where RCM diagnosis would determine lesion definite outcome (excision or digital
      follow-up). RESULTS: Reflectance confocal microscopy examination was performed
      for 41% of 1005 patients enrolled. In two-thirds of these cases RCM influenced
      the lesion outcome. The systematic application of RCM for equivocal lesions saved
      over 50% of benign lesions from unnecessary excision. The number needed to excise
      a melanoma was 6.8 with RCM examination, compared with a hypothetical 14.6
      without RCM evaluation. CONCLUSIONS: Reflectance confocal microscopy as a second
      level examination to dermatoscopy proved to be highly accurate in diagnosis and
      reduced the number of unnecessary excisions. Improved accuracy, considering that
      RCM enabled the detection of the six melanomas (2%) in the group of 308 lesions
      eligible for follow-up, also minimizes the risk of referring a melanoma to
      digital dermatoscopy monitoring, and potentially losing the patient to follow-up.

PMID- 24891082
TI  - Psychometric properties and clinical relevance of the adolescent sleep hygiene
      scale in Dutch adolescents.
AB  - OBJECTIVE: This study investigated reliability, validity, and clinical relevance
      of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. METHODS: The
      Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents
      and 112 adolescents with insomnia. Their sleep variables were measured using
      sleep logs and questionnaires. From the insomnia group, scores were also obtained
      after six weeks of cognitive behavioral therapy for insomnia (n=58) or waiting
      list (n=22). RESULTS: The full scale of the ASHS had acceptable internal
      consistency. The results showed moderate to strong correlations of the ASHS
      (domains) with sleep quality, sleep duration and chronic sleep reduction.
      Furthermore, the Dutch ASHS was able to discriminate between normal sleepers and
      adolescents with insomnia, and scores of adolescents with insomnia improved after
      treatment. CONCLUSIONS: These findings confirm the importance of sleep hygiene in
      adolescent sleep, and contribute to the validity of the ASHS and its
      applicability in research and clinical practice.

PMID- 24891084
TI  - A gold coordination compound as a chemical probe to unravel aquaporin-7 function.
AB  - Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many
      physiological functions. Aquaporin-based modulators are predicted to have
      potential utility in the treatment of several diseases, as well as chemical tools
      to assess AQPs function in biological systems. We recently reported gold(III)
      compounds as human AQP3 inhibitors, with Auphen as the most potent of the series.
      In this work, we assessed the modulation of aquaporin-7 (AQP7) expressed in an
      adipocyte cell model and show that Auphen significantly inhibits mouse and human
      AQP7. By homology modeling and molecular docking it was possible to identify the
      thioether groups of methionine residues, in particular Met47, as likely
      candidates for binding to the gold(III) complex. Our data point to Auphen as a
      useful chemical tool to detect AQP7 function. It might constitute a basis to
      develop inhibitors with improved affinity towards different aquaglyceroporin
      isoforms. 

PMID- 24891085
TI  - Phytol derivatives as drug resistance reversal agents.
AB  - Phytol was chemically transformed into fifteen semi-synthetic derivatives, which
      were evaluated for their antibacterial and drug resistance reversal potential in
      combination with nalidixic acid against E. coli strains CA8000 and DH5alpha. The
      pivaloyl (4), 3,4,5-trimethoxybenzoyl (9), 2,3-dichlorobenzoyl (10), cinnamoyl
      (11), and aldehyde (14) derivatives of phytol ((2E,7R,11R)-3,7,11,15-tetramethyl
      2-hexadecen-1-ol) were evaluated by using another antibiotic, tetracycline,
      against the MDREC-KG4 clinical isolate of E. coli. Derivative 4 decreased the
      maximal inhibitory concentration (MIC) of the antibiotics by 16-fold, while
      derivatives 9, 10, 11, and 14 reduced MIC values of the antibiotics up to
      eightfold against the E. coli strains. Derivatives 4, 9, 10, 11, and 14 inhibited
      the ATP-dependent efflux pump; this was also supported by their in silico binding
      affinity and down-regulation of the efflux pump gene yojI, which encodes the
      multidrug ATP-binding cassette transporter protein. This study supports the
      possible use of phytol derivatives in the development of cost-effective
      antibacterial combinations. 

PMID- 24891086
TI  - Single-fraction stereotactic body radiation therapy for sinonasal malignant
      melanoma.
AB  - BACKGROUND: A rare head and neck disease that may benefit from definitive or
      palliative stereotactic body radiation therapy (SBRT) is sinonasal malignant
      melanoma. These tumors can be very aggressive and often lead to severe epistaxis
      and significant mass effect. Results from only a handful of head and neck
      sinonasal malignant melanoma treated with SBRT are available in the current
      literature. METHODS: The following reports on 2 cases of sinonasal malignant
      melanoma that recurred postoperatively and were subsequently treated at Roswell
      Park with SBRT. Both were treated with a single fraction of 15 Gy. RESULTS:
      Nearly instant relief of their chronic epistaxis and complete responses were seen
      in both patients. One patient is alive and free of disease 7 years after
      radiation. CONCLUSION: These patients with sinonasal malignant melanoma achieved
      symptomatic relief of severe bleeding and airway issues from single-fraction
      SBRT. SBRT should be considered as a treatment option in patients with
      unresectable sinonasal malignant melanoma.

PMID- 24891087
TI  - Cell manufacturing for clinical applications.

PMID- 24891089
TI  - Distraction osteogenesis for complex foot deformities: Gigli saw midfoot
      osteotomy with external fixation.
AB  - Open midfoot wedge osteotomy correction can cause neurovascular compromise,
      requires extensive exposure, sacrifices normal joints, and shortens the foot. We
      used a minimally invasive technique to treat complex foot deformities by
      combining percutaneous Gigli saw midfoot osteotomy, circular external fixation,
      and acute, gradual, or gradual with acute manipulation correction. The medical
      records of 23 patients (26 feet) with complex foot deformities (congenital, 18
      feet; neuromuscular, 4 feet; post-traumatic, 3 feet; malunion, 1 foot) who had
      undergone treatment within an 18-year period (1990 through 2007) were
      retrospectively reviewed. We also performed the procedure on 10 cadaveric limbs
      to determine whether anatomic structures were at risk. Correction was achieved in
      all feet. The mean duration of external fixation treatment was 4.2 (range 3 to 7)
      months. The mean follow-up duration was 4.7 (range 2 to 18) years. A significant
      difference was observed in the pre- and postoperative, lateral view, talar-first
      metatarsal angle (p = .001). Minor complications (4 feet) consisted of bony
      exostoses. Major complications included recurrent deformity in 3 feet and sural
      nerve entrapment in 1 foot. Two patients had mild and one moderate foot pain.
      Three patients had impaired gait function; the remaining patients had functional
      gait. The mean interval until wearing regular shoes after external fixation
      removal was 2.3 (range 1 to 4) months. All but 1 of the patients were satisfied
      with the final results. We observed no cadaveric neurovascular injury. Our
      results have shown that percutaneous Gigli saw midfoot osteotomy can be performed
      without neurovascular injury and is capable of successfully correcting complex
      foot deformities.

PMID- 24891090
TI  - Functional outcome and patient satisfaction after displaced intra-articular
      calcaneal fractures: a comparison among open, percutaneous, and nonoperative
      treatment.
AB  - The aim of the present study was to compare the outcomes of patients with a
      displaced calcaneal fracture treated by open reduction and internal fixation
      (ORIF), percutaneous treatment, or nonoperative methods. A retrospective cohort
      study was conducted at a level I trauma center of patients with a displaced intra
      articular calcaneal fracture treated from January 1, 2002 to December 31, 2011.
      The patient-reported outcome measures included the Foot Function Index, American
      Orthopaedic Foot and Ankle Society hindfoot scale, Short Form-36, the EQ-5D from
      the EuroQol Group, and a 10-point visual analog scale. Clinical data were
      collected from 169 patients, and questionnaires were obtained from 78 patients
      (18 nonoperatively, 27 ORIF, and 33 percutaneously). The late intervention rate
      was significantly greater in the percutaneous group (n = 18; 30%) than in the
      ORIF group (n = 6; 12%) or the nonoperative group (n = 8; 13%; p = .030).
      Significantly more disability was reported in the nonoperative group (median Foot
      Function Index score, 40 points) than in the ORIF group (median, 16 points; p =
      .010) or in the percutaneous group (median, 21 points; p = .034). In conclusion,
      the operatively treated patients (ORIF and percutaneous treatment) reported
      better functional outcome scores (Foot Function Index and American Orthopaedic
      Foot and Ankle Society hindfoot scale) than did the nonoperatively treated
      patients.

PMID- 24891088
TI  - The serodominant secreted effector protein of Salmonella, SseB, is a strong CD4
      antigen containing an immunodominant epitope presented by diverse HLA class II
      alleles.
AB  - Detailed characterization of the protective T-cell response in salmonellosis is a
      pressing unmet need in light of the global burden of human Salmonella infections
      and the likely contribution of CD4 T cells to immunity against this intracellular
      infection. In previous studies screening patient sera against antigen arrays,
      SseB was noteworthy as a serodominant target of adaptive immunity, inducing
      significantly raised antibody responses in HIV-seronegative compared with
      seropositive patients. SseB is a secreted protein, part of the Espa superfamily,
      localized to the bacterial surface and forming part of the translocon of the type
      III secretion system (T3SS) encoded by Salmonella pathogenicity island 2. We
      demonstrate here that SseB is also a target of CD4 T-cell immunity, generating a
      substantial response after experimental infection in human volunteers, with
      around 0.1% of the peripheral repertoire responding to it. HLA-DR/peptide binding
      studies indicate that this protein encompasses a number of peptides with ability
      to bind to several different HLA-DR alleles. Of these, peptide 11 (p11) was shown
      in priming of both HLA-DR1 and HLA-DR4 transgenic mice to contain an
      immunodominant CD4 epitope. Analysis of responses in human donors showed immunity
      focused on p11 and another epitope in peptide 2. The high frequency of SseB
      reactive CD4 T cells and the broad applicability to diverse HLA genotypes coupled
      with previous observations of serodominance and protective vaccination in mouse
      challenge experiments, make SseB a plausible candidate for next-generation
      Salmonella vaccines.

PMID- 24891091
TI  - Modular stem fixed-bearing total ankle replacement: prospective results of 23
      consecutive cases with 3-year follow-up.
AB  - In the present report, the 3-year outcomes of 23 consecutive patients treated
      with a modular stem fixed-bearing total ankle replacement are described. Pain,
      functional impairment, and disability were assessed annually using a visual
      analog scale. Complications and additional procedures also were recorded.
      Compared with preoperative pain (8.4 +/- 1.4), functional impairment (8.7 +/-
      2.3), and disability (3.0 +/- 2.5), there were statistically significant
      postoperative improvements at 1 year (pain, 2.6 +/- 1.6; functional impairment,
      3.1 +/- 2.1; disability, 0.9 +/- 1.2), 2 years (pain, 1.5 +/- 1.3; functional
      impairment, 1.9 +/- 1.4; disability, 0.6 +/- 1.4), and 3 years (pain, 1.3 +/-
      1.3; functional impairment, 1.9 +/- 1.9; disability, 0.4 +/- 0.9; p <= .001).
      Pain, function, and disability significantly improved postoperatively from 1 to 2
      years (p <= .008) and from 1 to 3 years (p <= .008). The reductions in pain,
      functional impairment, and disability were maintained from 2 to 3 years (p >=
      .08). Nine complications (39.1%) were encountered: 1 deep infection, 2 pulmonary
      embolisms, 3 wounds, 1 ectopic bone formation, 1 stiff joint, and 1 talar
      subsidence. In the 3-year follow-up period, 3 patients (13.0%) required
      additional procedures after the immediate postoperative phase. Our results have
      demonstrated that modular stem fixed-bearing prostheses can be implanted in a
      predictable and consistent fashion with resultant improvements in pain, function,
      and disability. Future studies evaluating the clinical outcomes after modular
      stem fixed-bearing total ankle replacement are warranted.

PMID- 24891092
TI  - Behavioral skills training to improve installation and use of child passenger
      safety restraints.
AB  - The risk for serious injury and death to children during motor vehicle accidents
      can be greatly reduced through the correct use of child passenger safety
      restraints (CPSRs). Unfortunately, most CPSRs are installed or used incorrectly.
      This study examined the effectiveness of behavioral skills training (BST) to
      teach 10 participants to install rear-facing CPSRs correctly using a multiple
      baseline design. Results show that installation errors were common for all
      participants during baseline. After BST, all 10 participants were able to install
      the rear-facing CPSR without error. An extension probe to assess whether the
      skills taught during BST extended to forward-facing installation showed that each
      participant made at least 1 critical error. 

PMID- 24891093
TI  - Characterization and functional analysis of voltage-dependent anion channel 1
      (VDAC1) from orange-spotted grouper (Epinephelus coioides).
AB  - The voltage-dependent anion channel (VDAC) is a highly conserved integral protein
      of mitochondria in different eukaryotic species. It forms a selective channel in
      the mitochondrial outer membrane that serves as the controlled pathway for small
      metabolites and ions. In this study, a VDAC gene, EcVDAC1, was isolated from
      orange-spotted grouper (Epinephelus coioides). The EcVDAC1 exhibits ubiquitous
      expression in various tissues of orange-spotted grouper and is upregulated in
      liver, gill, and spleen after stimulation with lipopolysaccharides (LPS).
      Subcellular localization analysis shows that the EcVDAC1 protein colocalized with
      the mitochondria. A caspase-3 assay demonstrates that overexpression of the
      EcVDAC1 induced apoptotic cell death in fathead minnow cells. The data presented
      in this study provide new information regarding the relationship between LPS and
      the EcVDAC1 gene, suggesting that the fish VDAC1 gene may play an important role
      in antibacterial immune response. 

PMID- 24891094
TI  - The influence of sinus membrane thickness upon membrane perforation during
      transcrestal sinus lift procedure.
AB  - OBJECTIVES: Schneiderian membrane perforation is one of the main complications
      during sinus augmentation. The reasons may be associated with surgical technique,
      septum, inadequate ridge height, and membrane thickness. However, reports that
      used cone-beam computed tomography (CBCT) to quantify the thickness of sinus
      membrane were limited. The aims of this retrospective study were: to study the
      correlation between membrane thickness and perforation rate during transcrestal
      sinus lift and to propose a classification system of sinus membrane thickness
      based upon CBCT data. MATERIAL AND METHODS: One hundred and twenty-two subjects
      who received dental implant restorations over posterior maxilla with a total of
      185 transcrestal sinus lift procedures between years 2010 to 2013 were selected
      consequently. Each patient selected had to have taken CBCT in the initial
      examination and immediately after surgery. The membrane thickness, perforation
      rate, residual bone height, and elevated bone height were recorded and processed
      for statistical analysis. RESULTS: The mean thickness of the Schneiderian
      membrane was 1.78 +/- 1.99 mm. There was a significant correlation between
      membrane thickness and perforation rate (P < 0.05), and the perforation rate was
      higher in thicker (>=3 mm) and thinner membrane (<=0.5 mm). Among the thickness
      group, Class B (between >=1 and <2 mm) had the lowest perforation rate. No
      significant difference was between the perforation and the membrane morphology. A
      negative relationship between residual bone height and membrane thickness was
      found. Trend showed that in the thicker and the thinner residual bone height, the
      higher the perforation rate would be. CONCLUSIONS: There was a significant
      correlation between membrane thickness and perforation rate. The perforation rate
      was lowest when the thickness was 1.5-2 mm.

PMID- 24891095
TI  - Testicular seminoma presenting as unilateral gynecomastia.

PMID- 24891096
TI  - Cost-utility analysis of a pharmacotherapy follow-up for elderly nursing home
      residents in Spain.
AB  - OBJECTIVES: To compare the cost-effectiveness of a pharmacotherapy follow-up for
      elderly nursing home (NH) residents with that of usual care. DESIGN: Prospective
      observational study with a concurrent control group conducted over 12 months.
      SETTING: Fifteen NHs in Andalusia assigned to control (n = 6) or intervention (n
      = 9). PARTICIPANTS: Residents aged 65 and older. INTERVENTION: Pharmacotherapy
      follow-up. MEASUREMENTS: Negative outcomes associated with medication, health
      related quality of life, cost, quality-adjusted life-year (QALY), and incremental
      cost-effectiveness ratio (ICER). ICERs were estimated for three scenarios:
      unadjusted cost per QALY (first scenario), costs adjusted for baseline prescribed
      medication and QALYs adjusted for baseline utility score (second scenario), and
      costs and QALYs adjusted for a fuller set of baseline characteristics (third
      scenario). RESULTS: Three hundred thirty-two elderly residents were enrolled: 122
      in the control group and 210 in the intervention group. The general practitioner
      accepted 88.7% (274/309) of pharmacist recommendations. Pharmacist interventions
      reduced the average number of prescribed medication by 0.47 drugs (P < .001),
      whereas the average prescribed medication increased by 0.94 drugs in the control
      group (P < .001). Both groups reported a lower average EuroQol-5D utility score
      after 12 months (intervention, -0.0576, P = .002; control, -0.0999, P = .003).
      For the first scenario, usual care dominated pharmacotherapy follow-up (was less
      effective and more expensive). Adjusted ICERs were ? 3,899/QALY ($5,002/QALY) for
      the second scenario and ? 6,574/QALY ($8,433/QALY) for the third scenario. For a
      willingness to pay of ? 30,000/QALY ($38,487/QALY), the probabilities of the
      pharmacotherapy follow-up being cost-effective were 35% for the first scenario,
      78% for the second, and 76% for the third. CONCLUSION: Pharmacotherapy follow-up
      is considered cost-effective for elderly NH residents in Spain.

PMID- 24891097
TI  - Total mercury concentrations in anadromous Northern Dolly Varden from the
      northwestern Canadian Arctic: a historical baseline study.
AB  - Previous research has documented the significance of total mercury (THg) as a
      northern contaminant in general and of fish in particular. While much research
      has been devoted to documenting both spatial and temporal changes in THg in
      consumed fish, little effort has been directed at understanding patterns of THg
      in Dolly Varden (Salvelinus malma), a prized subsistence species throughout the
      western North American Arctic. Here we report historical THg concentrations for
      anadromous Dolly Varden from 10 populations in the Yukon and Northwest
      Territories sampled across a range of latitudes (67-69 degrees N) and longitudes
      (136-141 degrees W) between the years 1988-91. Unadjusted mean THg concentrations
      ranged from 15 to 254 ng/g wet weight. Length-adjusted THg concentrations were
      significantly different among sites, but were not related to latitude or
      longitude. Within and among populations, THg was significantly related to fork
      length, age, delta(15)N, and delta(13)C, with the variation in THg found among
      populations being best explained by size. The data serve as an important baseline
      against which future changes in THg levels in this important subsistence fishery
      may be compared to determine the significance of any observed trends.

PMID- 24891098
TI  - The nanoscale carbon p-n junction between carbon nanotubes and N,B-codoped holey
      graphene enhances the catalytic activity towards selective oxidation.
AB  - We show the spontaneous formation of multiple nanoscale carbon p-n junctions
      between carbon nanotubes (CNTs) and negatively charged N,B-codoped graphene
      (NBG). Application of these carbon nanocomposites to catalyze the selective
      oxidation of an organic amine to imine resulted in an unprecedented activity
      under mild conditions. 

PMID- 24891100
TI  - Fluorescent studies on the interaction of DNA and ternary lanthanide complexes
      with cinnamic acid-phenanthroline and antibacterial activities testing.
AB  - Twelve lanthanide complexes with cinnamate (cin(-) ) and 1,10-phenanthroline
      (phen) were synthesized and characterized. Their compositions were assumed to be
      RE(cin)3 phen (RE(3+)  = La(3+) , Pr(3+) , Nd(3+) , Sm(3+) , Eu(3+) , Gd(3+) ,
      Tb(3+) , Dy(3+) , Ho(3+) , Tm(3+) , Yb(3+) , Lu(3+) ). The interaction mode
      between the complexes and DNA was investigated by fluorescence quenching
      experiment. The results indicated the complexes could bind to DNA and the main
      binding mode is intercalative binding. The fluorescence quenching constants of
      the complexes increased from La(cin)3 phen to Lu(cin)3 phen. Additionally, the
      antibacterial activity testing showed that the complexes exhibited excellent
      antibacterial ability against Escherichia coli, and the changes of antibacterial
      ability are in agreement with that of the fluorescence quenching constants.

PMID- 24891099
TI  - Regulation of dynamin oligomerization in cells: the role of dynamin-actin
      interactions and its GTPase activity.
AB  - Dynamin is a 96-kDa protein that has multiple oligomerization states that
      influence its GTPase activity. A number of different dynamin effectors, including
      lipids, actin filaments, and SH3-domain-containing proteins, have been implicated
      in the regulation of dynamin oligomerization, though their roles in influencing
      dynamin oligomerization have been studied predominantly in vitro using
      recombinant proteins. Here, we identify higher order dynamin oligomers such as
      rings and helices in vitro and in live cells using fluorescence lifetime imaging
      microscopy (FLIM). FLIM detected GTP- and actin-dependent dynamin oligomerization
      at distinct cellular sites, including the cell membrane and transition zones
      where cortical actin transitions into stress fibers. Our study identifies a major
      role for direct dynamin-actin interactions and dynamin's GTPase activity in the
      regulation of dynamin oligomerization in cells. 

PMID- 24891101
TI  - Interventions for caregivers of someone with an eating disorder: a meta-analysis.
AB  - OBJECTIVE: A variety of interventions have been developed for caregivers of
      people with an eating disorder either to help them cope with the burden and
      distress that commonly accompanies this role or to make them more effective at
      providing support. The aim of the study is to perform a meta-analysis of
      quantitative studies that have described the impact of these interventions on
      caregivers. METHOD: Electronic databases were searched between September 2001 and
      September 2013. Thirteen studies were finally selected for inclusion. Pooled
      effect size estimates were summarized. Meta-regressions were used to determine
      whether type of intervention, team, measure used or risk of bias were effect
      modifiers of the relationship. We also summarized the content and form (amount of
      professional help) of the interventions. RESULTS: Most interventions produced a
      moderate sized reduction in carer distress and a small/moderate reduction in
      carer burden and expressed emotion post treatment and these changes were
      maintained over follow-up. DISCUSSION: Carer distress, burden and expressed
      emotion can be reduced by a variety of psychoeducational interventions and these
      changes are sustainable over time. The interventions themselves are easy to
      disseminate and deliver.

PMID- 24891102
TI  - Percutaneous minimally invasive fetoscopic surgery for spina bifida aperta. Part
      I: surgical technique and perioperative outcome.
AB  - OBJECTIVES: To analyze the current technical approach of percutaneous minimal
      access fetoscopic closure of spina bifida aperta (SBA) and provide an overview of
      its development in ovine and human fetuses. METHODS: Minimal-access percutaneous
      fetoscopic closure of SBA was performed at the German Center for Fetal Surgery &
      Minimal-access Therapy (DZFT) in 51 human fetuses at 21.0-29.1 weeks of gestation
      (mean age, 23.7 weeks). Various parameters of surgical relevance for the success
      and safety of the procedure and the early perioperative outcome were analyzed
      retrospectively. In addition, information from the early clinical cases was
      examined to determine how this shaped development of the approach. RESULTS:
      Percutaneous minimal-access fetoscopic closure of SBA was performed with a high
      rate of technical success, regardless of placental or fetal position. All fetuses
      survived surgery, but there was one very early preterm delivery 1 week after the
      procedure and this neonate died immediately, from early postoperative
      chorioamnionitis. Of the 50 surviving fetuses, 44 (88%) were delivered at or
      beyond 30 weeks and 25 (50%) at or beyond 34 weeks of gestation. There was one
      neonatal death from an uinsuspected case of trisomy 13 and two infant deaths from
      Chiari-II malformation. CONCLUSIONS: Following an adequate learning curve,
      minimal-access fetoscopic surgery for fetal spina bifida can be performed with a
      high rate of technical success, regardless of placental position.

PMID- 24891103
TI  - Edwardsiella tarda-Induced cytotoxicity depends on its type III secretion system
      and flagellin.
AB  - Many Gram-negative bacteria utilize a type III secretion system (T3SS) to
      translocate virulence proteins into host cells to cause diseases. In responding
      to infection, macrophages detect some of the translocated proteins to activate
      caspase-1-mediated cell death, called pyroptosis, and secretion of
      proinflammatory cytokines to control the infection. Edwardsiella tarda is a Gram
      negative enteric pathogen that causes hemorrhagic septicemia in fish and both
      gastrointestinal and extraintestinal infections in humans. In this study, we
      report that the T3SS of E. tarda facilitates its survival and replication in
      murine bone marrow-derived macrophages, and E. tarda infection triggers
      pyroptosis of infected macrophages from mice and fish and increased secretion of
      the cytokine interleukin 1beta in a T3SS-dependent manner. Deletion of the
      flagellin gene fliC of E. tarda results in decreased cytotoxicity for infected
      macrophages and does not attenuate its virulence in a fish model of infection,
      whereas upregulated expression of FliC in the fliC mutant strain reduces its
      virulence. We propose that the host controls E. tarda infection partially by
      detecting FliC translocated by the T3SS, whereas the bacteria downregulate the
      expression of FliC to evade innate immunity. 

PMID- 24891104
TI  - Morphogenesis is not required for Candida albicans-Staphylococcus aureus intra
      abdominal infection-mediated dissemination and lethal sepsis.
AB  - Intra-abdominal polymicrobial infections cause significant morbidity and
      mortality. An established experimental mouse model of Staphylococcus aureus
      Candida albicans intra-abdominal infection results in ~60% mortality within 48 h
      postinoculation, concomitant with amplified local inflammatory responses, while
      monomicrobial infections are avirulent. The purpose of this study was to
      characterize early local and systemic innate responses during coinfection and
      determine the role of C. albicans morphogenesis in lethality, a trait involved in
      virulence and physical interaction with S. aureus. Local and systemic
      proinflammatory cytokines were significantly elevated during coinfection at early
      time points (4 to 12 h) compared to those in monoinfection. In contrast,
      microbial burdens in the organs and peritoneal lavage fluid were similar between
      mono- and coinfected animals through 24 h, as was peritoneal neutrophil
      infiltration. After optimizing the model for 100% mortality within 48 h, using
      3.5 * 10(7) C. albicans (5* increase), coinfection with C. albicans yeast-locked
      or hypha-locked mutants showed similar mortality, dissemination, and local and
      systemic inflammation to the isogenic control. However, coinfection with the
      yeast-locked C. albicans mutant given intravenously (i.v.) and S. aureus given
      intraperitoneally (i.p.) failed to induce mortality. These results suggest a
      unique intra-abdominal interaction between the host and C. albicans-S. aureus
      that results in strong inflammatory responses, dissemination, and lethal sepsis,
      independent of C. albicans morphogenesis. 

PMID- 24891106
TI  - Pyocyanin stimulates quorum sensing-mediated tolerance to oxidative stress and
      increases persister cell populations in Acinetobacter baumannii.
AB  - Acinetobacter baumannii and Pseudomonas aeruginosa are nosocomial pathogens with
      overlapping sites of infection. This work reports that the two can coexist stably
      in mixed-culture biofilms. In a study intended to improve our understanding of
      the mechanism of their coexistence, it was found that pyocyanin, produced by P.
      aeruginosa that generally eliminates competition from other pathogens, led to the
      generation of reactive oxygen species (ROS) in A. baumannii cells, which in
      response showed a significant (P <= 0.05) increase in production of enzymes,
      specifically, catalase and superoxide dismutase (SOD). This work shows for the
      first time that the expression of catalase and SOD is under the control of a
      quorum-sensing system in A. baumannii. In support of this observation, a quorum
      sensing mutant of A. baumannii (abaI::Km) was found to be sensitive to pyocyanin
      compared to its wild type and showed significantly (P <= 0.001) lower levels of
      the antioxidant enzymes, which increased on addition of 5 MUM N-(3
      hydroxydodecanoyl)-l-homoserine lactone. Likewise, in wild-type A. baumannii,
      there was a significant (P < 0.01) decrease in the level of anti-oxidant enzymes
      in the presence of salicylic acid, a known quencher of quorum sensing. In the
      presence of amikacin and carbenicillin, A. baumannii formed 0.07 and 0.02%
      persister cells, which increased 4- and 3-fold, respectively, in the presence of
      pyocyanin. These findings show that pyocyanin induces a protective mechanism in
      A. baumannii against oxidative stress and also increases its persistence against
      antibiotics which could be of clinical significance in the case of coinfections
      with A. baumannii and P. aeruginosa. 

PMID- 24891105
TI  - A specific polymorphism in Mycobacterium tuberculosis H37Rv causes differential
      ESAT-6 expression and identifies WhiB6 as a novel ESX-1 component.
AB  - The ESX-1 secreted virulence factor ESAT-6 is one of the major and most well
      studied virulence factors of Mycobacterium tuberculosis, given that its
      inactivation severely attenuates virulent mycobacteria. In this work, we show
      that clinical isolates of M. tuberculosis produce and secrete larger amounts of
      ESAT-6 than the widely used M. tuberculosis H37Rv laboratory strain. A search for
      the genetic polymorphisms underlying this observation showed that whiB6
      (rv3862c), a gene upstream of the ESX-1 genetic locus that has not previously
      been found to be implicated in the regulation of the ESX-1 secretory apparatus,
      presents a unique single nucleotide insertion in its promoter region in strains
      H37Rv and H37Ra. This polymorphism is not present in any of the other publicly
      available M. tuberculosis complex genomes or in any of the 76 clinical M.
      tuberculosis isolates analyzed in our laboratory. We demonstrate that in
      consequence, the virulence master regulator PhoP downregulates whiB6 expression
      in H37Rv, while it upregulates its expression in clinical strains. Importantly,
      reintroduction of the wild-type (WT) copy of whiB6 in H37Rv restored ESAT-6
      production and secretion to the level of clinical strains. Hence, we provide
      clear evidence that in M. tuberculosis--with the exception of the H37Rv strain-
      ESX-1 expression is regulated by WhiB6 as part of the PhoP regulon, which adds
      another level of complexity to the regulation of ESAT-6 secretion with a
      potential role in virulence adaptation.

PMID- 24891107
TI  - Colonization of cecum is important for development of persistent infection by
      Yersinia pseudotuberculosis.
AB  - Yersiniosis is a human disease caused by the bacterium Yersinia
      pseudotuberculosis or Yersinia enterocolitica. The infection is usually resolved
      but can lead to postinfectious sequelae, including reactive arthritis and
      erythema nodosum. The commonly used Yersinia mouse infection model mimics acute
      infection in humans to some extent but leads to systemic infection and eventual
      death. Here, we analyzed sublethal infection doses of Y. pseudotuberculosis in
      mice in real time using bioluminescent imaging and found that infections using
      these lower doses result in extended periods of asymptomatic infections in a
      fraction of mice. In a search for the site for bacterial persistence, we found
      that the cecum was the primary colonization site and was the site where the
      organism resided during a 115-day infection period. Persistent infection was
      accompanied by sustained fecal shedding of cultivable bacteria. Cecal patches
      were identified as the primary site for cecal colonization during persistence. Y.
      pseudotuberculosis bacteria were present in inflammatory lesions, in localized
      foci, or as single cells and also in neutrophil exudates in the cecal lumen. The
      chronically colonized cecum may serve as a reservoir for dissemination of
      infection to extraintestinal sites, and a chronic inflammatory state may trigger
      the onset of postinfectious sequelae. This novel mouse model for bacterial
      persistence in cecum has potential as an investigative tool to unveil a deeper
      understanding of bacterial adaptation and host immune defense mechanisms during
      persistent infection. 

PMID- 24891110
TI  - Staphylococcus aureus 'Down Under': contemporary epidemiology of S. aureus in
      Australia, New Zealand, and the South West Pacific.
AB  - The clinical and molecular epidemiology of Staphylococcus aureus disease has
      changed considerably over the past two decades, particularly with the emergence
      and spread of community-associated methicillin-resistant S. aureus (CA-MRSA)
      clones. Indeed, some of the first global descriptions of CA-MRSA were from remote
      indigenous communities in Western Australia, and from Pacific Peoples in New
      Zealand. The epidemiology of S. aureus infections in the South West Pacific has
      several unique features, largely because of the relative geographical isolation
      and unique indigenous communities residing in this region. In particular, a
      number of distinct CA-MRSA clones circulate in Australia and New Zealand, such as
      sequence type (ST) 93 methicillin-resistant S. aureus (MRSA) (Queensland clone)
      and clonal complex 75 S. aureus (Staphylococcus argenteus) in Australia, and ST30
      MRSA (Southwest Pacific clone) in New Zealand. In addition, there is a
      disproportionate burden of S. aureus disease in indigenous paediatric
      populations, particularly in remote Aboriginal communities in Australia, and in
      Pacific Peoples and Maori in New Zealand. In this review, we provide a
      contemporary overview of the clinical and molecular epidemiology of S. aureus
      disease in the South West Pacific region, with a particular focus on features
      distinct to this region.

PMID- 24891111
TI  - Kidney transplant access in the Southeastern United States: the need for a top
      down transformation.
AB  - End-stage renal disease (ESRD) and poverty are highly prevalent conditions in the
      Southeastern United States. The American Southeast also has some of the lowest
      attainments of health status among its constituents. Transplantation rates are
      particularly low in the Southeast compared with other regions of the United
      States. These low kidney transplantation rates in the Southeast likely reflect
      poor access to medical care. This disproportionate lack of access to medical care
      among ESRD patients in the Southeast reflects the convergence and interaction of
      socioeconomic and biologic forces at the patient level interacting with the
      financial and organizational structure of the health-care system. Improving
      kidney transplant access in the Southeast will take disruptive political,
      financial and health system changes whose scope transcends transplant centers and
      dialysis units. 

PMID- 24891109
TI  - Exposure to Bacillus anthracis capsule results in suppression of human monocyte
      derived dendritic cells.
AB  - The antiphagocytic capsule of Bacillus anthracis is a major virulence factor. We
      hypothesized that it may also mediate virulence through inhibition of the host's
      immune responses. During an infection, the capsule exists attached to the
      bacterial surface but also free in the host tissues. We sought to examine the
      impact of free capsule by assessing its effects on human monocytes and immature
      dendritic cells (iDCs). Human monocytes were differentiated into iDCs by
      interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) over 7 days in the presence of capsule derived from wild-type encapsulated
      B. anthracis Ames (WT) or a control preparation from an isogenic B. anthracis
      Ames strain that produces only 2% of the capsule of the WT (capA mutant). WT
      capsule consistently induced release of IL-8 and IL-6 while the capA mutant
      control preparation elicited either no response or only a minimal release of IL
      8. iDCs that were differentiated in the presence of WT capsule had increased side
      scatter (SSC), a measure of cellular complexity, when assessed by flow cytometry.
      iDCs differentiated in the presence of WT capsule also matured less well in
      response to subsequent B. anthracis peptidoglycan (Ba PGN) exposure, with reduced
      upregulation of the chemokine receptor CCR7, reduced CCR7-dependent chemotaxis,
      and reduced release of certain cytokines. Exposure of naive differentiated
      control iDCs to WT capsule did not alter cell surface marker expression but did
      elicit IL-8. These results indicate that free capsule may contribute to the
      pathogenesis of anthrax by suppressing the responses of immune cells and
      interfering with the maturation of iDCs. 

PMID- 24891112
TI  - The influence of morphology, follicle size and Bcl-2 and Bax transcripts on the
      developmental competence of bovine oocytes.
AB  - This study analysed two non-invasive oocyte selection methods in relation to in
      vitro embryo development capacity and expression of apoptosis-related genes.
      Selection was based on morphological quality of oocytes or follicle diameter.
      Oocytes were classified as grade I (GI >=3 layers compact cumulus cells and
      homogeneous cytoplasm; grade II (GII <=3 layers compact cells and homogeneous
      cytoplasm;, and grade III (GIII >=3 layers, but cells with slight expansion and
      slightly granulated cytoplasm). Blastocyst development was lower for GII (28.5%)
      than for GIII (47.7%, p < 0.05), and GI was similar to both (36.9%, p > 0.05).
      Relative expression of Bcl-2 gene was lower in the GI (1.0, p < 0.05) than in the
      GII (1.8) and GIII (2.2), which were not different (p > 0.05). There was no
      difference (p > 0.05) between GI (1.0), GII (0.92) and GIII (0.93) regarding the
      Bax transcript. However, the Bax and Bcl-2 transcript ratios in GII (Bax; 0.92
      and Bcl-2; 1.8) and GIII (Bax; 0.93 and Bcl-2; 2.2) were different (p < 0.05).
      Regarding oocytes from follicles of different sizes, cleavage and blastocyst
      rates for 1-3 mm (82.5; 23.7%) were lower (p < 0.05) than for 6-9 mm (95.6;
      41.1%), but similar (p > 0.05) to 3-6 mm (93.7; 35.4%), which were not different
      (p > 0.05). Regarding Bax and Bcl-2 expression, the oocytes were similar (p >
      0.05) for 1-3 mm (Bax; 1.0 and Bcl-2; 1.0), 3-6 mm (Bax; 1.0 and Bcl-2; 0.93) and
      6-9 mm (Bax; 0.92 and Bcl-2; 0.91). In conclusion, oocyte selection based on
      morphological appearance does not guarantee the success of embryonic development.
      Additionally, the absence of apoptosis is not necessarily a benefit for the
      development of oocytes. Bovine COCs with initial signs of atresia may be used for
      the in vitro production of embryos, and COCs taken from follicles >3 mm in
      diameter are better suited to in vitro embryo development.

PMID- 24891113
TI  - A Hospitalist mentoring program to sustain interest in healthcare careers in
      under-represented minority undergraduates.
AB  - BACKGROUND: Ethnic minorities in the United States have decreased access to
      healthcare and disproportionately high morbidity and mortality. There has been
      minimal growth in the number of minority physicians despite their important role
      in reducing health disparities. Under-represented minority (URM) undergraduate
      students are 50% less likely to maintain interest in medical careers. METHODS:
      Denver Health and the University of Colorado, Denver enrolled URM students
      interested in healthcare careers in a year-long, comprehensive program called the
      Healthcare Interest Program (HIP) that included pairing each student with a
      hospitalist for mentoring and job shadowing. At the end of the first year of HIP,
      students were surveyed, and 2 years later they were contacted for follow-up.
      RESULTS: Twenty-three students enrolled and all completed the program. Nineteen
      (83%) completed the survey and all "strongly agreed" that participating in HIP
      expanded their perceptions of what they might accomplish and increased their
      confidence in their ability to participate in a healthcare profession. Two-year
      follow-up was available for 21 students (91%). Twenty (95%) remained committed to
      a career in healthcare, 18 (86%) had graduated, and 6 (29%) were enrolled in
      postgraduate healthcare training. CONCLUSION: The interest of undergraduate
      minority prehealth students in healthcare careers may be maintained by
      participation in a multifaceted, year-long mentoring program such as HIP.

PMID- 24891108
TI  - Genes required for assembly of pili associated with the Helicobacter pylori cag
      type IV secretion system.
AB  - Helicobacter pylori causes numerous alterations in gastric epithelial cells
      through processes that are dependent on activity of the cag type IV secretion
      system (T4SS). Filamentous structures termed "pili" have been visualized at the
      interface between H. pylori and gastric epithelial cells, and previous studies
      suggested that pilus formation is dependent on the presence of the cag
      pathogenicity island (PAI). Thus far, there has been relatively little effort to
      identify specific genes that are required for pilus formation, and the role of
      pili in T4SS function is unclear. In this study, we selected 7 genes in the cag
      PAI that are known to be required for T4SS function and investigated whether
      these genes were required for pilus formation. cagT, cagX, cagV, cagM, and cag3
      mutants were defective in both T4SS function and pilus formation; complemented
      mutants regained T4SS function and the capacity for pilus formation. cagY and
      cagC mutants were defective in T4SS function but retained the capacity for pilus
      formation. These results define a set of cag PAI genes that are required for both
      pilus biogenesis and T4SS function and reveal that these processes can be
      uncoupled in specific mutant strains. 

PMID- 24891114
TI  - Insights into the decomposition of olefin metathesis precatalysts.
AB  - The decomposition of a series of benzylidene, methylidene, and 3
      phenylindenylidene complexes has been probed in alcohol solution in the presence
      of base. Tricyclohexylphosphane-containing precatalysts are shown to yield
      [RuCl(H)(H2)(PCy3)2] in isopropyl alcohol solutions, while 3-phenylindenylidene
      complexes lead to eta(5)-(3-phenyl)indenyl products. The potential-energy
      surfaces for the formation of the latter species have been probed using density
      functional theory studies.

PMID- 24891115
TI  - Sustained release of metformin via red blood cell accumulated sulfenamide
      prodrug.
AB  - Metformin is a first-line antidiabetic drug to treat type 2 diabetes. It is
      rapidly eliminated from plasma but also accumulated into red blood cells (RBCs)
      from which it is slowly released back into plasma. The aim of the study was to
      evaluate whether the amount of metformin in the RBCs could be increased by a
      sulfenamide prodrug approach, which could provide longer duration of metformin in
      systemic circulation. Pharmacokinetic properties of metformin and its cyclohexyl
      sulfenamide prodrug were evaluated in plasma and in whole blood after intravenous
      and oral administration in rats. Once the sulfenamide prodrug reached the
      bloodstream, it was rapidly and efficiently accumulated into the RBCs, where it
      was converted to metformin by free thiols. The RBC-whole blood ratio of metformin
      was increased approximately from 42% to 96% when metformin was administered
      intravenously as its sulfenamide prodrug, and the proportion of metformin in the
      RBCs was found to be concentration and time independent. Because metformin was
      slowly liberated into plasma, the prodrug showed a sustained-release
      pharmacokinetic profile and longer plasma half-life for metformin after oral
      administration. Therefore, this sulfenamide prodrug has great potential to
      improve metformin therapy as the daily doses could be reduced.

PMID- 24891117
TI  - CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO
      proteins through AKT.
AB  - Cluster of differentiation 166 (CD166) is a cell surface membrane protein, which
      is regarded as a valuable prognostic marker in several types of epithelial
      tumors. We previously reported that CD166 exerts its pro-carcinogenic role by
      enhancing YAP function in liver cancer cells. However, YAP cannot completely
      rescue the increased anti-carcinogenic effects by gene silencing of CD166, whose
      downstream effectors require further investigation. Here, we found that knockdown
      of CD166 inhibits phosphorylation of anti-carcinogenic FOXO proteins.
      Overexpression of CD166 led, not only to a faster protein degradation rate, but
      also a more accumulated ubiquitination of FOXO compared to the control. Moreover,
      overexpression of CD166 facilitated FOXO protein localization from the nuclear
      fraction to the cytosolic fraction, suggesting that CD166 modulates FOXO protein
      stability through alteration of their subcellular localization. In addition,
      simultaneous overexpression of CD166 partially reversed the evoked anti
      carcinogenic effects by overexpression of FOXO both in vitro and in vivo.
      Furthermore, CD166 knockdown-induced anti-carcinogenic effects and
      dephosphorylation of FOXO proteins were rescued by overexpression of AKT. In
      liver cancer tissues, we also observed that higher expression levels of CD166,
      phospho-AKT, total AKT and phospho-FOXO were correlated with lower expression
      levels of total FOXO, suggesting that the upregulation of CD166 leads to the
      activation of AKT, which in turn facilitates phosphorylation and degradation of
      FOXO. Taken together, our data demonstrate that AKT is an inter-mediator between
      the upstream regulator, CD166, and downstream effector, FOXO, in liver cancer
      cells. Disrupting the relationship between CD166 and the AKT/FOXO axis may serve
      as a novel therapeutic target for liver cancer patients.

PMID- 24891118
TI  - The adaptation of a school-based health promotion programme for youth with
      intellectual and developmental disabilities: a community-engaged research
      process.
AB  - BACKGROUND: Evidenced-based health promotion programmes for youth with
      intellectual and developmental disabilities (I/DD) are notably absent. Barriers
      include a lack of understanding of how to adapt existing evidence-based
      programmes to their needs, maximize inclusion and support mutual goals of health
      and autonomy. METHODS: We undertook a community-engaged process to adapt a school
      based nutrition intervention in a residential school for youth with I/DD. Focus
      groups and interviews with school staff elicited recommendations for adaptation
      strategies; these were then reviewed by an expert panel. RESULTS: Adaptations
      were developed to address needs in three categories: food-related challenges
      among students, adjusting to change and transition and social environment
      factors. Choice and heterogeneity were overarching themes across the adaptation
      categories. CONCLUSIONS: Future research should consider community-engaged
      approaches for adaptation so that youth with I/DD can participate and benefit
      from evidence-based health promotion programmes to their maximum potential.

PMID- 24891116
TI  - Comparison of younger and older breast cancer survivors and age-matched controls
      on specific and overall quality of life domains.
AB  - BACKGROUND: Younger survivors (YS) of breast cancer often report more
      survivorship symptoms such as fatigue, depression, sexual difficulty, and
      cognitive problems than older survivors (OS). This study sought to determine the
      effect of breast cancer and age at diagnosis on quality of life (QoL) by
      comparing 3 groups: 1) YS diagnosed at age 45 years or before, 2) OS diagnosed
      between 55 and 70, and 3) for the YSs, age-matched controls (AC) of women not
      diagnosed with breast cancer. METHODS: Using a large Eastern Cooperative Oncology
      Group (ECOG) database, 505 YS were recruited who were aged 45 years or younger
      when diagnosed and 622 OS diagnosed at 55 to 70 years of age. YS, OS, and AC were
      compared on physical, psychological, social, spiritual, and overall QoL
      variables. RESULTS: Compared to both AC and to OS, YS reported more depressive
      symptoms (P = .005) and fatigue (P < .001), poorer self-reported attention
      function (P < .001), and poorer sexual function (P < .001) than either comparison
      group. However, YS also reported a greater sense of personal growth (P < .001)
      and perceived less social constraint (P < .001) from their partner than AC.
      CONCLUSIONS: YS reported worse functioning than AC relative to depression,
      fatigue, attention, sexual function, and spirituality. Perhaps even more
      important, YS fared worse than both AC and OS on body image, anxiety, sleep,
      marital satisfaction, and fear of recurrence, indicating that YS are at greater
      risk for long-term QoL problems than survivors diagnosed at a later age.

PMID- 24891119
TI  - How clinicians manage access to opioid replacement therapy.
AB  - In Australia, people wait to access opioid replacement therapy (ORT). The aim of
      this study was to examine how clinicians (n = 35) prioritize consumers for opioid
      replacement therapy (ORT). The study used a methodology informed by a
      constructivist approach to grounded theory. Based on a scenario related to two
      consumers seeking admission to opioid replacement therapy (ORT), participants
      were asked to prioritize one for preferential admission and questioned about
      their decision-making. Clinicians were neither confident nor unanimous in their
      decision-making. Team involvement and work experience influenced their judgment.
      Differences between clinicians in regard to understanding risks and protective
      factors were identified. To support uniformity in managing treatment requests,
      clearer policy direction to gui clinician practice, and further exploration of
      how models of care and team involvement influence consumer outcomes, are
      recommended.

PMID- 24891121
TI  - Echocardiographic evaluation of congenital left ventricular outflow obstruction.
AB  - Left ventricular outflow obstructions (LVOTO) encompass a series of stenotic
      lesions beginning within the anatomic left ventricular outflow tract and ending
      in the descending thoracic aorta, occurring alone or in series. The degree of
      stenosis and hemodynamic consequences may vary from mild and well tolerated to
      severe and functionally limiting. The majority of LVOTO (with the exception of
      calcific and rheumatic aortic stenosis) are congenital in etiology.
      Echocardiography has become an integral tool in the assessment of patients with
      congenital heart disease. This article is a contemporary review of the clinical
      features of LVOTO and the role of echocardiography in this patient population. 

PMID- 24891122
TI  - Developmental temperature affects the expression of ejaculatory traits and the
      outcome of sperm competition in Callosobruchus maculatus.
AB  - The outcome of post-copulatory sexual selection is determined by a complex set of
      interactions between the primary reproductive traits of two or more males and
      their interactions with the reproductive traits of the female. Recently, a number
      of studies have shown the primary reproductive traits of both males and females
      express phenotypic plasticity in response to the thermal environment experienced
      during ontogeny. However, how plasticity in these traits affects the dynamics of
      sperm competition remains largely unknown. Here, we demonstrate plasticity in
      testes size, sperm size and sperm number in response to developmental temperature
      in the bruchid beetle Callosobruchus maculatus. Males reared at the highest
      temperature eclosed at the smallest body size and had the smallest absolute and
      relative testes size. Males reared at both the high- and low-temperature extremes
      produced both fewer and smaller sperm than males reared at intermediate
      temperatures. In the absence of sperm competition, developmental temperature had
      no effect on male fertility. However, under conditions of sperm competition,
      males reared at either temperature extreme were less competitive in terms of
      sperm offence (P(2)), whereas those reared at the lowest temperature were less
      competitive in terms of sperm defence (P(1)). This suggests the developmental
      pathways that regulate the phenotypic expression of these ejaculatory traits are
      subject to both natural and sexual selection: natural selection in the pre
      ejaculatory environment and sexual selection in the post-ejaculatory environment.
      In nature, thermal heterogeneity during development is commonplace. Therefore, we
      suggest the interplay between ecology and development represents an important,
      yet hitherto underestimated component of male fitness via post-copulatory sexual
      selection.

PMID- 24891120
TI  - Fractional factorial design to investigate stromal cell regulation of macrophage
      plasticity.
AB  - Understanding the regulatory networks which control specific macrophage
      phenotypes is essential in identifying novel targets to correct macrophage
      mediated clinical disorders, often accompanied by inflammatory events. Since
      mesenchymal stromal cells (MSCs) have been shown to play key roles in regulating
      immune functions predominantly via a large number of secreted products, we used a
      fractional factorial approach to streamline experimental evaluation of MSC
      mediated inflammatory macrophage regulation. Our macrophage reprogramming
      metrics, human bone marrow MSC attenuation of macrophage pro-inflammatory M1
      TNFalpha secretion and simultaneous enhanced expression of the M2 macrophage
      marker, CD206, were used as analysis endpoints. Objective evaluation of a panel
      of MSC secreted mediators indicated that PGE2 alone was sufficient in
      facilitating macrophage reprogramming, while IL4 only provided partial
      reprogramming. Inhibiting stromal cell PGE2 secretion with Indomethacin, reversed
      the macrophage reprogramming effect. PGE2 reprogramming was mediated through the
      EP4 receptor and indirectly through the CREB signaling pathway as GSK3 specific
      inhibitors induced M1 macrophages to express CD206. This reprogramming pathway
      functioned independently from the M1 suppression pathway, as neither CREB nor
      GSK3 inhibition reversed PGE2 TNF-alpha secretion attenuation. In conclusion,
      fractional factorial experimental design identified stromal derived PGE2 as the
      factor most important in facilitating macrophage reprogramming, albeit via two
      unique pathways.

PMID- 24891123
TI  - Fast computation of Hessian-based enhancement filters for medical images.
AB  - This paper presents a method for fast computation of Hessian-based enhancement
      filters, whose conditions for identifying particular structures in medical images
      are associated only with the signs of Hessian eigenvalues. The computational
      costs of Hessian-based enhancement filters come mainly from the computation of
      Hessian eigenvalues corresponding to image elements to obtain filter responses,
      because computing eigenvalues of a matrix requires substantial computational
      effort. High computational cost has become a challenge in the application of
      Hessian-based enhancement filters. Using a property of the characteristic
      polynomial coefficients of a matrix and the well-known Routh-Hurwitz criterion in
      control engineering, it is shown that under certain conditions, the response of a
      Hessian-based enhancement filter to an image element can be obtained without
      having to compute Hessian eigenvalues. The computational cost can thus be
      reduced. Experimental results on several medical images show that the method
      proposed in this paper can reduce significantly the number of computations of
      Hessian eigenvalues and the processing times of images. The percentage reductions
      of the number of computations of Hessian eigenvalues for enhancing blob- and
      tubular-like structures in two-dimensional images are approximately 90% and 65%,
      respectively. For enhancing blob-, tubular-, and plane-like structures in three
      dimensional images, the reductions are approximately 97%, 75%, and 12%,
      respectively. For the processing times, the percentage reductions for enhancing
      blob- and tubular-like structures in two-dimensional images are approximately 31%
      and 7.5%, respectively. The reductions for enhancing blob-, tubular-, and plane
      like structures in three-dimensional images are approximately 68%, 55%, and 3%,
      respectively. 

PMID- 24891125
TI  - Subthreshold delta-frequency resonance in thalamic reticular neurons.
AB  - The thalamic reticular nucleus (nRt) is an assembly of GABAergic projection
      neurons that participate in the generation of brain rhythms during synchronous
      sleep and absence epilepsy. NRt cells receive inhibitory and excitatory synaptic
      inputs, and are endowed with an intricate set of intrinsic conductances. However,
      little is known about how intrinsic and synaptic properties interact to generate
      rhythmic discharges in these neurons. In order to better understand this
      interaction, I studied the subthreshold responses of nRt cells to time-varying
      inputs. Patch-clamp recordings were performed in acute slices of rat thalamus
      (postnatal days 12-21). Sinusoidal current waveforms of linearly changing
      frequencies were injected into the soma, and the resulting voltage oscillations
      were recorded. At the resting membrane potential, the impedance profile showed a
      characteristic resonance at 1.7 Hz. The relative strength of the resonance was
      1.2, and increased with membrane hyperpolarization. Small suprathreshold current
      injections led to preferred spike generation at the resonance frequency. Bath
      application of ZD7288 or Cs(+) , inhibitors of the hyperpolarization-activated
      cation current (Ih ), transformed the resonance into low-pass behaviour, whereas
      the T-channel blockers mibefradil and Ni(2+) decreased the strength of the
      resonance. It is concluded that nRt cells have an Ih -mediated intrinsic
      frequency preference in the subthreshold voltage range that favours action
      potential generation in the delta-frequency band. 

PMID- 24891124
TI  - Arterial spin labeling-fast imaging with steady-state free precession (ASL-FISP):
      a rapid and quantitative perfusion technique for high-field MRI.
AB  - Arterial spin labeling (ASL) is a valuable non-contrast perfusion MRI technique
      with numerous clinical applications. Many previous ASL MRI studies have utilized
      either echo-planar imaging (EPI) or true fast imaging with steady-state free
      precession (true FISP) readouts, which are prone to off-resonance artifacts on
      high-field MRI scanners. We have developed a rapid ASL-FISP MRI acquisition for
      high-field preclinical MRI scanners providing perfusion-weighted images with
      little or no artifacts in less than 2 s. In this initial implementation, a flow
      sensitive alternating inversion recovery (FAIR) ASL preparation was combined with
      a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6
      mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4
      T (249 +/- 38 and 241 +/- 17 mL/min/100 g, respectively). The utility of this
      method was further demonstrated in the detection of significant perfusion
      deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion
      estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential
      perfusion in the renal cortex and medulla. Overall, the ASL-FISP technique
      provides a rapid and quantitative in vivo assessment of tissue perfusion for high
      field MRI scanners with minimal image artifacts.

PMID- 24891126
TI  - An evaluation of the quality of Emergency Nurse Practitioner services for
      patients presenting with minor injuries to one rural urgent care centre in the
      UK: a descriptive study.
AB  - AIMS AND OBJECTIVES: To evaluate the quality of the emergency nurse practitioner
      service provided to people presenting to a rural urgent care centre with minor
      injuries. The three objectives that were focused were an evaluation of the safety
      and effectiveness of the emergency nurse practitioner service, an assessment of
      patients' satisfaction with the emergency nurse practitioner service and a
      determination of factors that may enhance the quality of the emergency nurse
      practitioner service. BACKGROUND: Urgent care centres have become increasingly
      prevalent across the UK. Emergency nurse practitioner services at these rural
      urgent care centres remain largely unevaluated. This study attempts to redress
      this deficit by evaluating the quality of an emergency nurse practitioner service
      in relation to the care of patients presenting with minor injuries to a rural
      urgent care centre. DESIGN: This descriptive study used a case-note review and a
      survey design with one open-ended exploratory question. METHODS: Patient views
      were collected using a self-completed questionnaire and a data extraction tool to
      survey patients' case notes retrospectively. RESULTS: Despite comparatively low
      total length-of-stay times, most patients felt they had enough time to discuss
      things fully with the emergency nurse practitioner. Although emergency nurse
      practitioners routinely impart injury advice, feedback from some patients
      suggests a need for the provision of more in-depth information regarding their
      injury. The vast majority (97.3%) of patients felt that the quality of the
      emergency nurse practitioner service was of a high standard. Contrary to some
      other studies, the findings in this study indicate that patient satisfaction is
      not influenced by waiting times. CONCLUSIONS: Emergency nurse practitioners in
      rural urgent care centres have the potential to deliver a safe and effective
      quality service that is reflected in high levels of patient satisfaction.
      RELEVANCE TO CLINICAL PRACTICE: This study provides some evidence to support the
      continued expansion of the emergency nurse practitioner service in rural settings
      in the UK.

PMID- 24891127
TI  - Synergistic acceleration in the osteogenesis of human mesenchymal stem cells by
      graphene oxide-calcium phosphate nanocomposites.
AB  - Nanocomposites consisting of oblong ultrathin plate shaped calcium phosphate
      nanoparticles and graphene oxide microflakes were synthesized and have
      demonstrated markedly synergistic effect in accelerating stem cell
      differentiation to osteoblasts. 

PMID- 24891128
TI  - FNAB of benign thyroid nodules with papillary hyperplasia: a cytological and
      histological evaluation.
AB  - BACKGROUND: Benign thyroid nodules with papillary hyperplasia (BTN-PH) are
      sometimes misinterpreted cytologically as papillary thyroid carcinoma (PTC). We
      evaluated a fine-needle aspiration biopsy (FNAB) series of BTN-PH to identify the
      causes of diagnostic error and to better define its cytologic criteria. METHODS:
      A total of 48 FNAB cases of histologically confirmed BTN-PHs from 44 patients
      were identified from our archives. The available cytological and histological
      slides were reviewed and scored for 10 cytomorphological features. Fifteen FNAB
      cases of classical PTC were also reviewed for comparison. RESULTS: The FNAB
      diagnoses for the 48 BTN-PHs were: benign, 18; suspicious for malignancy (S-PTC),
      12); atypia of undetermined significance/follicular lesion of undetermined
      significance (AUS/FLUS), 10; follicular neoplasm, 5; malignant (PTC), 2; and
      nondiagnostic, 1. The extent of PH in the corresponding histology was highest in
      FNAB cases diagnosed as S-PTC/PTC versus all other categories (54% vs 27%; P =
      .0084). Papillary cytoarchitectural features were present in 53% of FNAB cases
      overall and in 89% of cases diagnosed as S-PTC/PTC (P = .0093). Nuclei were
      smaller in FNABs of BTN-PH compared with PTC (mean diameter/range, 8.2/6-12 vs
      14.2/7-26 MUm, respectively; P = .0001). Twenty-six percent of BTN-PHs contained
      cytoplasmic pigment. All FNAB cases diagnosed as S-PTC/PTC had focal nuclear
      atypia including grooves (87.5%), enlargement and crowding (75%), and chromatin
      pallor and pseudoinclusions (25%); however, the extent of nuclear atypia was
      significantly less than in the control group of PTCs (P < .0001). CONCLUSIONS:
      BTN-PH represents a significant pitfall in thyroid FNABs in which it can be
      misinterpreted as S-PTC/PTC. Cytologic clues to this pitfall include limited and
      variable nuclear atypia, small nuclear size, and cytoplasmic pigment.

PMID- 24891129
TI  - Human-animal chimera: a neuro driven discussion? Comparison of three leading
      European research countries.
AB  - Research with human-animal chimera raises a number of ethical concerns,
      especially when neural stem cells are transplanted into the brains of non-human
      primates (NHPs). Besides animal welfare concerns and ethical issues associated
      with the use of embryonic stem cells, the research is also regarded as
      controversial from the standpoint of NHPs developing cognitive or behavioural
      capabilities that are regarded as "unique" to humans. However, scientists are
      urging to test new therapeutic approaches for neurological diseases in primate
      models as they better mimic human physiology than all current animal models. As a
      response, various countries have issued reports on the topic. Our paper
      summarizes the ethical issues raised by research with human-animal brain chimeras
      and compares the relevant regulatory instruments and different recommendations
      issued in national reports from three important European research nations:
      Germany, Switzerland and the United Kingdom. We assess and discuss the focus and
      priorities set by the different reports, review various reasons for and
      perspectives on the importance of the brain in chimera research, and identify
      critical points in the reports that warrant further specification and debate. 

PMID- 24891130
TI  - Existential risks: exploring a robust risk reduction strategy.
AB  - A small but growing number of studies have aimed to understand, assess and reduce
      existential risks, or risks that threaten the continued existence of mankind.
      However, most attention has been focused on known and tangible risks. This paper
      proposes a heuristic for reducing the risk of black swan extinction events. These
      events are, as the name suggests, stochastic and unforeseen when they happen.
      Decision theory based on a fixed model of possible outcomes cannot properly deal
      with this kind of event. Neither can probabilistic risk analysis. This paper will
      argue that the approach that is referred to as engineering safety could be
      applied to reducing the risk from black swan extinction events. It will also
      propose a conceptual sketch of how such a strategy may be implemented: isolated,
      self-sufficient, and continuously manned underground refuges. Some
      characteristics of such refuges are also described, in particular the
      psychosocial aspects. Furthermore, it is argued that this implementation of the
      engineering safety strategy safety barriers would be effective and plausible and
      could reduce the risk of an extinction event in a wide range of possible (known
      and unknown) scenarios. Considering the staggering opportunity cost of an
      existential catastrophe, such strategies ought to be explored more vigorously. 

PMID- 24891131
TI  - "Click" chemistry mildly stabilizes bifunctional gold nanoparticles for sensing
      and catalysis.
AB  - A large family of bifunctional 1,2,3-triazole derivatives that contain both a
      polyethylene glycol (PEG) chain and another functional fragment (e.g., a polymer,
      dendron, alcohol, carboxylic acid, allyl, fluorescence dye, redox-robust metal
      complex, or a beta-cyclodextrin unit) has been synthesized by facile "click"
      chemistry and mildly coordinated to nanogold particles, thus providing stable
      water-soluble gold nanoparticles (AuNPs) in the size range 3.0-11.2 nm with
      various properties and applications. In particular, the sensing properties of
      these AuNPs are illustrated through the detection of an analogue of a warfare
      agent (i.e., sulfur mustard) by means of a fluorescence "turn-on" assay, and the
      catalytic activity of the smallest triazole-AuNPs (core of 3.0 nm) is excellent
      for the reduction of 4-nitrophenol in water. 

PMID- 24891132
TI  - Pharmacogenetics, plasma concentrations, clinical signs and EEG during propofol
      treatment.
AB  - A variety of techniques have been developed to monitor the depth of anaesthesia.
      Propofol's pharmacokinetics and response vary greatly, which might be explained
      by genetic polymorphisms. We investigated the impact of genetic variations on
      dosage, anaesthetic depth and recovery after total intravenous anaesthesia with
      propofol. A total of 101 patients were enrolled in the study. The plasma
      concentration of propofol during anaesthesia was measured using high-performance
      liquid chromatography. EEG was monitored during the surgical procedure as a
      measure of anaesthetic depth. Pyrosequencing was used to determine genetic
      polymorphisms in CYP2B6, CYP2C9, the UGTIA9-promotor and the GABRE gene. The
      correlation between genotype and to plasma concentration at the time of loss of
      consciousness (LOC), the total induction dose, the time to anaesthesia, eye
      opening and clearance were investigated. EEG monitoring showed that the majority
      of the patients had not reached a sufficient level of anaesthetic depth
      (subdelta) at the time of loss of consciousness despite a high induction dose of
      propofol. Patients with UGT1A9-331C/T had a higher propofol clearance than those
      without (p = 0.03) and required a higher induction dose (p = 0.03). The patients
      with UGT1A9-1818T/C required a longer time to LOC (p = 0.03). The patients with
      CYP2C9*2 had a higher concentration of propofol at the time of LOC (p = 0.02).
      The polymorphisms in the metabolizing enzymes and the receptor could not explain
      the large variation seen in the pharmacokinetics of propofol and the clinical
      response seen. At LOC, the patients showed a large difference in EEG pattern. 

PMID- 24891133
TI  - Dual antiplatelet therapy with or without oral anticoagulation in the
      postdischarge management of acute coronary syndrome patients with an indication
      for long term anticoagulation: a systematic review.
AB  - Currently, there is a lack of consensus among guidelines for the postdischarge
      treatment of patients presenting with acute coronary syndrome (ACS) who have a
      long-term indication for anticoagulation. We conducted a systematic review
      comparing the safety and effectiveness of dual antiplatelet therapy (DAPT) and
      triple therapy (TT; defined as DAPT plus an oral anticoagulant) in patients with
      ACS and a long-term indication for anticoagulation. We searched for clinical
      studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews
      published between January 1995 and September 2013. Each investigator screened and
      abstracted data, assessed applicability and quality, and graded the strength of
      evidence. Meta-analysis of direct comparison was performed when outcomes and
      follow-up periods were comparable. Fourteen observational studies were identified
      that contained comparative effectiveness data on DAPT versus TT. No difference in
      the odds of mortality (OR 1.04, 95% CI 0.59-1.83) or stroke (OR 1.01, 95% CI 0.38
      2.67) at 1-5 years was found between TT and DAPT. Major bleeding at 1-5 years (OR
      1.46, 95% CI 1.07-2.00) and nonfatal MI at 1-5 years (OR 1.85, 95% CI 1.13-3.02)
      occurred more frequently in patients receiving TT. The results of this systematic
      review demonstrate that treatment with TT was associated with increased rates of
      nonfatal MI and major bleeding when compared with treatment with DAPT in the
      postdischarge management of ACS patients with an indication for oral
      anticoagulation. Until results of ongoing randomized trials assessing
      antithrombotic therapies define optimal management strategies, the current
      analysis suggests using caution when prescribing TT to these patients.

PMID- 24891134
TI  - Electrospun nanofibers-mediated on-demand drug release.
AB  - A living system has a complex and accurate regulation system with intelligent
      sensor-processor-effector components to enable the release of vital bioactive
      substances on demand at a specific site and time. Stimuli-responsive polymers
      mimic biological systems in a crude way where an external stimulus results in a
      change in conformation, solubility, or alternation of the hydrophilic/hydrophobic
      balance, and consequently release of a bioactive substance. Electrospinning is a
      straightforward and robust method to produce nanofibers with the potential to
      incorporate drugs in a simple, rapid, and reproducible process. This feature
      article emphasizes an emerging area using an electrospinning technique to
      generate biomimetic nanofibers as drug delivery devices that are responsive to
      different stimuli, such as temperature, pH, light, and electric/magnetic field
      for controlled release of therapeutic substances. Although at its infancy, the
      mimicry of these stimuli-responsive nanofibers to the function of the living
      systems includes both the fibrous structural feature and bio-regulation function
      as an on demand drug release depot. The electrospun nanofibers with extracellular
      matrix morphology intrinsically guide cellular drug uptake, which will be highly
      desired to translate the promise of drug delivery for the clinical success. 

PMID- 24891135
TI  - CD4+/CD25+ T cells suppress autologous CD4+/CD25- lymphocytes and secrete
      granzyme B during acute and chronic hepatitis C.
AB  - We aimed to verify whether CD4(+)/CD25(+) T cells suppress CD4(+) T cells and
      secrete Granzyme B (GZB) during acute and chronic hepatitis C (CHC) infection. We
      enrolled 50 subjects: 20 patients with CHC (Group A), 15 healthy individuals
      (Group B), 10 patients with acute hepatitis C later evolved to persistent
      infection (Group C) and five patients who resolved hepatitis C virus infection
      during acute phase (Group D). We analysed, on enrolled subjects CD4(+)/CD25(+) T
      cells and related GZB production as well as Annexin V activity. Patients from
      Groups A and C had higher frequency and function of peripheral Treg cells than
      healthy individuals. Groups A and C showed an increase in spot-forming colonies
      (SFCs) of GZB compared with Group B (P < 0.01, Mann-Whitney U-test).
      CD4(+)/CD25(+) T cells in Group D had a lower number of GZB SFCs compared with
      Groups A and C but higher number than Group B (P < 0.01 Mann-Whitney U-test).
      Annexin V production was higher in Groups A and C than B or D. Patients having
      acute and chronic hepatitis C have a higher Treg frequency and function in
      peripheral blood than healthy controls or those resolving the infection in acute
      phase secreting GZB, probably inducing apoptosis.

PMID- 24891136
TI  - Illness perceptions of cancer patients: relationships with illness
      characteristics and coping.
AB  - OBJECTIVE: Illness perceptions have proven to be predictive of coping and
      adjustment in many chronically ill patients. However, insights into illness
      perceptions of cancer patients are scarce. The purpose of the present study was
      to explore how a heterogeneous sample of cancer patients perceive their illness.
      We also examined the relationships between cancer patients' illness perceptions,
      their illness characteristics, and their coping strategies. METHODS: Participants
      were 325 cancer patients of a generic nationwide longitudinal panel study among
      cancer patients in the Netherlands. They completed the revised Illness Perception
      Questionnaire (Winter 2011/2012) and the Mental Adjustment to Cancer Scale
      (Spring 2012). Analyses of variance and linear regression analyses were
      conducted. RESULTS: Patients' views on the chronicity of cancer vary, but many
      believe their illness to be long-lasting. Furthermore, they strongly believe the
      cancer treatment to be effective. People with skin cancer experience relatively
      little negative consequences (p < 0.01). Recently treated patients experience
      more negative consequences (p < 0.001) and perceive their illness as more chronic
      (p < 0.01). Surprisingly, neither perceptions of treatment control nor
      perceptions of personal control are related to specific ways of coping. However,
      more passive ways of coping were more often found in patients who perceived their
      illness as long-lasting, more emotionally burdening, and having more negative
      consequences. CONCLUSIONS: Our findings suggest that cancer patients might
      benefit more from support to alleviate the perceived severity and threat of their
      illness rather than from (further) strengthening their control beliefs.

PMID- 24891137
TI  - Therapy of endocrine disease: treatment of malignant pheochromocytoma and
      paraganglioma.
AB  - Metastatic pheochromocytomas and paragangliomas (MPPs) present clinicians with
      three major challenges: scarcity, complexity of characterization, and
      heterogeneous behavior and prognosis. As with the treatment for all
      neuroendocrine tumors, the control of hormonal symptoms and tumor growth is the
      main therapeutic objective in MPP patients. A significant number of MPP patients
      still die from uncontrolled hormone secretion. In addition, the management of
      MPPs remains palliative. Steps forward include proper characterization of MPP
      patients at large cancer referral centers with multidisciplinary teams; improved
      strategies to stratify patients prognostically; and implementation of trials
      within national and international networks. Progress in the molecular
      characterization and staging of MPPs constitutes the basis for significant
      treatment breakthroughs. 

PMID- 24891138
TI  - Gender differences in sclerostin and clinical characteristics in type 1 diabetes
      mellitus.
AB  - BACKGROUND: Sclerostin is an osteocyte-derived inhibitor of the Wnt/beta-catenin
      signaling pathway, which acts as a negative regulator of bone formation.
      Published data on sclerostin levels in type 1 diabetes mellitus (T1DM) are few.
      OBJECTIVE: To evaluate gender differences in sclerostin serum levels and the
      association among sclerostin, bone mass, bone metabolism, and the main clinical
      characteristics of subjects with T1DM. DESIGN AND METHODS: A total of 69 patients
      with T1DM (mean age, 33.7+/-8.1; 49% males) were enrolled in this cross-sectional
      study in a clinical research center. Bone mineral density was measured by
      phalangeal quantitative ultrasound (QUS); bone turnover markers (urinary
      pyridinoline, deoxypyridinoline (D-PYR), and urine hydroxyproline (OH-PRO) to
      evaluate bone resorption; serum bone alkaline phosphatase and BGP to evaluate
      bone formation) and sclerostin were assessed. RESULTS: D-PYR and sclerostin were
      significantly higher in women when compared with men (P=0.04). A disease duration
      >15 years was associated with higher sclerostin levels (P=0.03). Bone turnover
      markers and QUS parameters were not correlated with sclerostin. A significant
      negative correlation was observed among QUS parameters, BMI, and OH-PRO.
      Sclerostin serum levels were correlated with homocysteine (r=-0.34, P=0.005) and
      vitamin B12 (r=-0.31, P=0.02). Generalized linear model showed that
      macroangiopathy was the only predictor of sclerostin serum levels (beta=-11.8,
      95% CI from -21.9 to -1.7; P=0.02). CONCLUSIONS: Our data demonstrate that women
      with T1DM exhibit higher sclerostin levels than men and that circulating
      sclerostin is not associated with bone turnover markers and phalangeal QUS
      measurements. Macroangiopathy was associated with sclerostin levels.

PMID- 24891140
TI  - Hermaphrodite life history and the maintenance of partial selfing in experimental
      populations of Caenorhabditis elegans.
AB  - BACKGROUND: Classic population genetics theory predicts that mixed reproductive
      systems, where self reproduction (selfing) and outcrossing co-exist, should not
      be as common as they are in nature. One means of reconciling theory with
      observations is to recognize that sexual conflict between males and
      hermaphrodites and/or constraints in the allocation of resources towards sex
      functions in hermaphrodites can balance the fitness components of selfing and
      outcrossing. RESULTS: Using experimental evolution in Caenorhabditis elegans, we
      test whether the adaptive maintenance of partial selfing is due to sexual
      conflict and/or to the evolution of sex allocation towards male function in
      hermaphrodites. For this, we characterized the reproductive schedule and
      longevity patterns in hermaphrodites under selfing and under outcrossing with
      naive males that did not have the opportunity to evolve with them. A shift in
      reproductive schedule towards earlier reproduction would be indicative of
      adaptation in our imposed life-cycle, while longevity is expected to evolve as a
      response to the harm that males impinge on hermaphrodites upon mating. To
      determine adaptation in the absence of constraints in sex allocation, we also
      characterized the life history of females that reproduced during experimental
      evolution through obligate mating with males. As expected with adaptation, we
      find that after 100 generations of experimental evolution, selfing hermaphrodites
      and females showed improved reproduction at earlier ages. We did not observe
      similar reproductive shifts in outcrossed hermaphrodites. We further find
      increased longevity in outcrossed females after evolution but not in outcrossed
      hermaphrodites, a result that indicates that sexual conflicts were likely more
      prevalent under male-female evolution than under male-hermaphrodite evolution.
      CONCLUSIONS: Taken together, our findings suggest that the adaptive maintenance
      of partial selfing during C. elegans experimental evolution resulted from the
      evolution of sex allocation towards male function in hermaphrodites.

PMID- 24891142
TI  - Flexible nitrogen-doped graphene/carbon nanotube/Co3O4 paper and its oxygen
      reduction activity.
AB  - Due to the demand of an efficient, inexpensive and scalable synthesis of oxygen
      reduction reaction (ORR) catalyst for practical application in fuel cell, we
      demonstrate a facile strategy to fabricate the flexible nitrogen-doped
      graphene/carbon nanotube/Co3O4 (NG/CNT/Co3O4) paper catalyst. In the hydrothermal
      process, the in situ formation of Co3O4 nanoparticles, reduction of GO and doping
      of nitrogen species occur simultaneously in the assembled paper in ammonia
      solution. Because of the synergistic effects of three active components and the
      spacing effect of CNTs and Co3O4 nanoparticles on avoiding the re-aggregation of
      assembled graphene nanosheets, the free-standing NG/CNT/Co3O4 paper exhibits an
      enhanced ORR catalytic performance with stable durability and strong methanol
      tolerant capability, indicating promising potential as ORR electrocatalyst in
      practical applications. 

PMID- 24891141
TI  - High pressure germination of Bacillus subtilis spores with alterations in levels
      and types of germination proteins.
AB  - AIMS: Examine effects of different levels and types of nutrient germinant
      receptors (GRs) and other germination proteins on Bacillus subtilis spore
      germination by a moderate high pressure (mHP) (150 megaPascals (MPa)) that
      triggers germination through GRs, and a very high pressure (vHP) (550 MPa) that
      triggers spore germination independent of GRs. METHODS AND RESULTS: The Moderate
      HP (mHP) and vHP germination kinetics of B. subtilis spores with large variations
      in levels of GRs and other germination proteins, including the GerD protein and
      the SpoVA proteins that comprise a spore membrane channel that is likely opened
      by vHP were measured. CONCLUSIONS: GR levels were the major factor determining
      mHP germination rates. However, other factors modulated mHP germination rates
      including (i) relative levels of individual GRs (GerA, GerB, GerK), as mHP
      affected different GRs differently; (ii) levels of a recently identified small
      protein that may be a GR subunit; and (iii) a dominant negative mutation in gerD
      that eliminates GR-dependent nutrient germination. In contrast, the alterations
      in germination proteins had no major effect on vHP germination, except for
      reduction of SpoVA protein levels. SIGNIFICANCE AND IMPACT OF THE STUDY: With the
      increasing use of HP for food processing, this study provides new information on
      factors that modulate HP germination of spores for potential application of HP
      technology to achieve food sterility.

PMID- 24891139
TI  - Loss of dopamine phenotype among midbrain neurons in Lesch-Nyhan disease.
AB  - OBJECTIVE: Lesch-Nyhan disease (LND) is caused by congenital deficiency of the
      purine recycling enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt).
      Affected patients have a peculiar neurobehavioral syndrome linked with reductions
      of dopamine in the basal ganglia. The purpose of the current studies was to
      determine the anatomical basis for the reduced dopamine in human brain specimens
      collected at autopsy. METHODS: Histopathological studies were conducted using
      autopsy tissue from 5 LND cases and 6 controls. Specific findings were replicated
      in brain tissue from an HGprt-deficient knockout mouse using immunoblots, and in
      a cell model of HGprt deficiency by flow-activated cell sorting (FACS). RESULTS:
      Extensive histological studies of the LND brains revealed no signs suggestive of
      a degenerative process or other consistent abnormalities in any brain region.
      However, neurons of the substantia nigra from the LND cases showed reduced
      melanization and reduced immunoreactivity for tyrosine hydroxylase (TH), the rate
      limiting enzyme in dopamine synthesis. In the HGprt-deficient mouse model,
      immunohistochemical stains for TH revealed no obvious loss of midbrain dopamine
      neurons, but quantitative immunoblots revealed reduced TH expression in the
      striatum. Finally, 10 independent HGprt-deficient mouse MN9D neuroblastoma lines
      showed no signs of impaired viability, but FACS revealed significantly reduced TH
      immunoreactivity compared to the control parent line. INTERPRETATION: These
      results reveal an unusual phenomenon in which the neurochemical phenotype of
      dopaminergic neurons is not linked with a degenerative process. They suggest an
      important relationship between purine recycling pathways and the neurochemical
      integrity of the dopaminergic phenotype.

PMID- 24891143
TI  - Organochlorine pesticide levels in breast milk in Guerrero, Mexico.
AB  - In Mexico, organochlorine pesticides were used in public health and agriculture
      programs, causing chronic exposure to the population. Human breast milk samples
      were collected from 171 mothers who were residents from Guerrero, Mexico.
      Analysis was carried out by gas chromatography. Median concentrations (mg/kg on
      fat basis) for the following pesticides were: HCB, 0.009; beta-HCH, 0.004;
      pp'DDE, 0.760; op'DDT, 0.016; pp'DDT, 0.045; and Sigma-DDT, 0.833. These values
      are lower than in other States in Mexico, and in some countries where the use of
      these pesticides was banned more than 30 years ago. Differences were found in
      HCB, pp'DDE and pp'DDT concentrations in groups divided according to age (p <
      0.05). The older age groups had higher concentrations, except for the comparison
      between groups 21-23/24-28 years, which were 0.913 and 0.530 mg/kg of pp'DDE,
      respectively. Given the restrictions on use, a greater decrease in organochlorine
      pesticide levels in human milk is expected in a few years.

PMID- 24891144
TI  - Sublethal toxic effects of nonylphenol ethoxylate and nonylphenol to Moina
      macrocopa.
AB  - The aim of this paper was to examine the sublethal toxic effects of nonylphenol
      ethoxylate (NP10EO), its primary degradation product nonylphenol (NP), and their
      mixture on Moina macrocopa. Chronic toxicity tests were carried out by using
      sublethal chemical concentrations. Results showed that all treatments reduced the
      survivorship, body length, and reproduction of M. macrocopa with NP being 10 %-20
      % more toxic to M. macrocopa than NP10EO. Results also indicated that the toxic
      effects of NP10EO and NP mixture on M. macrocopa were more severe than that of
      any single chemical alone. At the highest concentration in this experiment, 0.337
      mg L(-1) NP10EO plus 0.0154 mg L(-1) NP treatment caused the survivorship of M.
      macrocopa to zero, neonates number of reproductions to zero, 45.5 % reduction in
      the body length, and 88 % reduction in the total neonates number.

PMID- 24891145
TI  - Would the elimination of the capacity to suffer solve ethical dilemmas in
      experimental animal research?
AB  - The use of genetic engineering to enhance the welfare of laboratory animals can
      reduce the amount of suffering in current neuroscience research paradigms. In
      particular, for some forms of basic research, we can use welfare-enhanced animals
      to reduce harms to animals without sacrificing any of the scientific validity. In
      another group of experiments, we can use welfare-enhanced animals to dramatically
      reduce the number of unprotected animals enduring aversive procedures. Many of
      the objections to using welfare-enhanced animals for food production do not apply
      to their use in research, since genetic knockout techniques are already used
      routinely in research for human ends and since there is no risk for human health.
      Furthermore, examples of recent knockout experiments suggest that we already
      have, or are very close to having, the capacity to reduce suffering in
      laboratories via genetic engineering. If we are truly committed to balancing the
      advancement of science with the welfare of animals, this option should be further
      explored. 

PMID- 24891146
TI  - Nonlinear measures and dynamics in psychophysiology of consciousness.
AB  - According to recent findings nonlinear dynamic processes related to neural chaos
      and complexity likely play a crucial role in neural synchronization of
      distributed neural activities that enable information integration and conscious
      experience. Disturbances in these interactions produce patterns of temporal and
      spatial disorganization with decreased or increased functional connectivity and
      complexity that underlie specific changes of perceptual and cognitive states.
      These perceptual and cognitive changes may be characterized by neural chaos with
      significantly increased brain sensitivity that may underlie sensitization and
      kindling, and cognitive hypersensitivity in some mental disorders. Together these
      findings suggest that processes related to more irregular neural states with
      higher complexity that may lead to neural chaos, negatively affect information
      integration and processing in the brain, and may influence disintegrated
      conscious experience. 

PMID- 24891147
TI  - Reticulocytosis and anemia are associated with an increased risk of death and
      stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease.
AB  - Prior analyses of the Cooperative Study of Sickle Cell Disease (CSSCD) newborn
      cohort identified elevated white blood cell (WBC) count, low baseline hemoglobin
      and dactylitis between the ages of 1 and 2 years as markers of severe disease.
      Reticulocytosis was also associated with severe disease. Here, we further
      analyzed data collected on enrolled CSSCD infants for the predictive value of
      those markers for stroke and death later in life. Three hundred fifty-four CSSCD
      subjects were identified who had absolute reticulocyte counts (ARC) measured
      during infancy (2 to 6 months of age). Infants with higher ARC had significantly
      increased risk of stroke or death during childhood; lower hemoglobin levels also
      increased the risk but to a lesser degree than ARC. WBC levels and dactylitis
      were not predictive of death or stroke. These data suggest that reticulocytosis
      among asymptomatic infants with sickle cell anemia is associated with an
      increased risk of death or stroke during childhood.

PMID- 24891148
TI  - When is a seamless study desirable? Case studies from different pharmaceutical
      sponsors.
AB  - BACKGROUND: Inferentially seamless studies are one of the best-known adaptive
      trial designs. Statistical inference for these studies is a well-studied problem.
      Regulatory guidance suggests that statistical issues associated with study
      conduct are not as well understood. Some of these issues are caused by the need
      for early pre-specification of the phase III design and the absence of sponsor
      access to unblinded data. Before statisticians decide to choose a seamless
      IIb/III design for their programme, they should consider whether these pitfalls
      will be an issue for their programme. METHODS: We consider four case studies.
      Each design met with varying degrees of success. We explore the reasons for this
      variation to identify characteristics of drug development programmes that lend
      themselves well to inferentially seamless trials and other characteristics that
      warn of difficulties. RESULTS: Seamless studies require increased upfront
      investment and planning to enable the phase III design to be specified at the
      outset of phase II. Pivotal, inferentially seamless studies are unlikely to allow
      meaningful sponsor access to unblinded data before study completion. This limits
      a sponsor's ability to reflect new information in the phase III portion.
      CONCLUSIONS: When few clinical data have been gathered about a drug, phase II
      data will answer many unresolved questions. Committing to phase III plans and
      study designs before phase II begins introduces extra risk to drug development.
      However, seamless pivotal studies may be an attractive option when the clinical
      setting and development programme allow, for example, when revisiting dose
      selection.

PMID- 24891149
TI  - Prevalence of macrosomia and its risk factors in china: a multicentre survey
      based on birth data involving 101,723 singleton term infants.
AB  - BACKGROUND: Macrosomia, defined as a birthweight at least 4000 g, is a public
      health problem because of its adverse influences on maternal and neonatal
      outcomes. Studies show that there is an increasing prevalence of macrosomia
      births in developing countries. However, information on the epidemiology of
      macrosomia is limited in China. This study aimed to determine the prevalence and
      geographic variability of macrosomia in China and risk factors that can be
      targeted for intervention. METHODS: A hospital-based, cross-sectional survey was
      conducted in 14 provinces in China, covering a wide range of geographic areas.
      The medical records of 101,723 singleton term infants born in 39 hospitals during
      2011 were reviewed. Multiple logistic regression analysis was used to examine the
      associations between demographic characteristics and the risk of macrosomia.
      RESULTS: The total prevalence of macrosomia was 7.3%. The prevalence varied
      between provinces, ranging from 4.1% to 13.4%. The prevalence of macrosomia in
      northern China (8.5%) was significantly higher than that in southern China
      (5.6%). Logistic regression analyses showed that risk of macrosomia was
      positively associated with maternal age, pre-pregnant body mass index (BMI),
      gravidity, parity, maternal height, gestational weight gain (GWG), gestational
      diabetes mellitus (GDM), and male fetal sex. Maternal BMI, gestational week, and
      GWG were the three risk factors most strongly associated with macrosomia.
      CONCLUSIONS: The prevalence of macrosomia varied dramatically between different
      areas of China. High pre-pregnancy BMI and GWG represent main modifiable risk
      factors for macrosomia and need more attention from health care providers.

PMID- 24891150
TI  - Combined effects of drying methods, extract concentration, and film thickness on
      efficacy of antimicrobial chitosan films.
AB  - An idea of using a suitable drying method to minimize the loss of added
      antimicrobial agent and, at the same time, to modify the structure, and hence the
      release characteristics of chitosan films was proposed. Chitosan film-forming
      solution was incorporated with galangal extract (0% and 1.5% w/w) and formed into
      films with the thickness of 15 and 30 MUm via hot air drying (HD) (40  degrees C)
      and low-pressure superheated steam drying (LPSSD) (70  degrees C, 10 kPa). The
      extract retention, release characteristics, and antimicrobial efficacy of the
      films were then assessed; fresh-cut cantaloupe was used as the test food
      material, while Staphylococcus aureus was the test pathogenic microorganism. The
      retention and release of 1,8-cineole, a major bioactive compound in the galangal
      extract, was monitored during 5-d storage at 25  degrees C. The film swelling was
      also evaluated and their results used to interpret the release characteristics of
      1,8-cineole from the films to the cantaloupe. At the same thickness, the films
      prepared by HD had lower extract retention and higher degree of swelling, thus
      exhibiting faster extract release and lower antimicrobial efficacy than the films
      prepared by LPSSD. Within the same drying method, the increased film thickness
      led to higher extract retention and antimicrobial efficacy. The concentration of
      the extract in the cantaloupe matched well with the extract retention and release
      characteristics as well as the antimicrobial efficacy of the films. PRACTICAL
      APPLICATION: The results of this work illustrate the feasibility of using a
      suitable drying technology to improve the quality of antimicrobial films from
      edible biopolymer and form the basis for future development of an improved
      antimicrobial film production process.

PMID- 24891151
TI  - Association between early glycemic control and improvements in markers of
      coagulation and fibrinolysis in patients with septic shock-induced stress
      hyperglycemia.
AB  - PURPOSE: The purpose of this study is to evaluate the coagulation and
      inflammatory profiles in septic shock patients with baseline hyperglycemia under
      glycemic control. METHODS: Prospective, observational study conducted in an
      intensive care unit of a university hospital, including 41 septic shock
      nondiabetic patients with hyperglycemia (n = 21) or normoglycemia (n = 20)
      profiles at baseline. Hyperglycemic patients received a glucose control protocol
      (target glycemia, <150 mg/dL). Metabolic, inflammatory, and coagulation markers
      were measured at baseline and after 24 hours. RESULTS: Median glycemic values
      between groups were different at baseline but not after 24 hours. Baseline
      coagulation profile was similar in both groups with elevated levels of
      coagulation markers, reduced factor VII, protein C, and antithrombin activities
      and fibrinolysis impairment. Normoglycemic patients had unchanged coagulation
      markers after 24 hours. After treatment, previously hyperglycemic patients
      exhibited increased plasminogen concentrations (P = .03) and reduced levels of
      plasminogen activator inhibitor 1 (P = .01) and tissue plasminogen activator (P =
      .03) as compared with baseline. They also had higher factor VII (P = .03),
      protein C (P = .04), and antithrombin (P = .04) activities than normoglycemic
      patients. Inflammatory markers were elevated in both groups and improved after 24
      hours, independently of the glycemic profile. CONCLUSIONS: Glycemic control
      during septic shock is associated with improvements in coagulation and
      fibrinolysis parameters compared with baseline and normoglycemic patients.

PMID- 24891152
TI  - Serum lipid profile, cytokine production, and clinical outcome in patients with
      severe sepsis.
AB  - PURPOSE: The purpose of the study is to evaluate the prevalence and clinical
      significance of hypolipidemia and the relationship to cytokine concentrations and
      outcomes in septic patients. MATERIALS AND METHODS: A prospective study was
      undertaken including 50 patients with severe sepsis due to community-acquired
      infections. Serum concentrations of total cholesterol, triglyceride, high-density
      lipoprotein cholesterol (HDL-C), and low-density lipoprotein as well as tumor
      necrosis factor alpha (TNF-alpha), interleukin (IL) 6, IL-8, IL-10, and
      transforming growth factor (TGF) beta1 were determined on admission and days 3
      and 10 during hospitalization. RESULTS: Of the 50 patients enrolled, 28 survived,
      whereas 22 died during their hospital stay. Sepsis survivors had significantly
      higher HDL-C concentrations than nonsurvivors, whereas all patients with HDL-C
      values greater than 25 mg/dL survived. Baseline levels of TGF-beta1 were
      significantly higher in survivors. High-density lipoprotein levels correlated
      inversely with TNF-alpha, IL-6, and IL-10 concentrations and positively with
      baseline TGF-beta1 levels. Independent risk factors of mortality were IL-10
      levels on day 3, whereas HDL-C concentration on admission was related to
      survival. CONCLUSIONS: Low cholesterol and lipoprotein concentrations are
      detected in septic patients, especially in individuals with poor outcome. High
      density lipoprotein cholesterol concentration seems to be an early independent
      predictive marker of survival in severe sepsis.

PMID- 24891153
TI  - Anions in pre- and post-blast consumer fireworks by capillary electrophoresis.
AB  - Consumer fireworks are a heterogeneous group of pyrotechnic items widely used by
      citizens around the world. There are a wide number of forensic cases related to
      consumer fireworks that require knowing their chemical composition and variety of
      designs to conduct accurate and comprehensive analyses. In this research paper, a
      selection of six consumer firework types (firecracker, rocket, pyrotechnic
      fountain, pyrotechnic battery, sparkler, and smoke bomb) is physically described
      and their anionic compositions are determined. Preblast (fuses and charges)
      samples and postblast residues of the different consumer fireworks were analyzed
      by CE in order to determine their anionic composition. Different types of
      chemical compositions in fuses and pyrotechnic charges were determined, although
      they were not related to any type of item. Additionally, several discrepancies
      were found between the analytical results and the declared item compositions.
      Regarding postblast residues, a huge variety of anions were identified and
      attributed to some unconsumed starting materials and different chemical reactions
      occurring during combustion. 

PMID- 24891154
TI  - Mn oxide-silver composite nanowires for improved thermal stability, SERS and
      electrical conductivity.
AB  - Redox transformation reaction between aqueous AgNO3 and Mn(CH3COO)2 at low
      temperature (~80  degrees C) has been adopted for industrial-scale production of
      uniform Ag-MnOOH composite nanowires for the first time. Varying amounts of
      incorporated Ag in the composite retain the 1D morphology of the composite.
      Nanowires upon annealing evolve Ag-MnO2 nanocomposites, once again with the
      retention of the parental morphology. Just 4 % of silver incorporation in the
      composite demonstrates metal-like conducting performance from the corresponding
      semiconducting material. Transition of MnO2 to Mn2O3 to Mn3O4 takes place upon
      heat treatment in relation to successive increase in Ag concentrations in the
      nanowires. The composites offer resistance to the observed oxide transformation.
      This is evidenced from the progressive increase in transition temperature. In
      situ Raman, ex situ thermal and XRD analysis corroborate the fact. The composite
      with 12 % Ag offers resistance to the transformation of MnO2, which is also
      verified from laser heating. Importantly, Ag nanoparticle incorporation is proved
      to offer a thermally stable and better surface enhanced Raman scattering (SERS)
      platform than the individual components. Both the Ag-MnOOH and Ag-MnO2
      nanocomposites with 8 atomic % Ag show the best SERS enhancement (enhancement
      factor ~10(10)). The observed enhancement relates to charge transfer as well as
      electromagnetic effects.

PMID- 24891155
TI  - Fish or n3-PUFA intake and body composition: a systematic review and meta
      analysis.
AB  - Obesity is a major public health issue and an important contributor to the global
      burden of chronic disease and disability. Studies indicate that fish and omega-3
      polyunsaturated fatty acids (n3-PUFA) supplements may help prevent cardiovascular
      and metabolic diseases. However, the effect of fish oil on body composition is
      still uncertain, so we performed a systematic review of randomized controlled
      trials and the first meta-analysis on the association between fish or fish oil
      intake and body composition measures. We found evidence that participants taking
      fish or fish oil lost 0.59 kg more body weight than controls (95% confidence
      interval [CI]: -0.96 to -0.21). Treatment groups lost 0.24 kg m(-2) (body mass
      index) more than controls (-0.40 to -0.08), and 0.49 % more body fat than
      controls (-0.97 to -0.01). Fish or fish oil reduced waist circumference by 0.81
      cm (-1.34 to -0.28) compared with control. There was no difference for fat mass
      and lean body mass. Further research is needed to confirm or refute our findings
      and to reveal possible mechanisms by which n3-PUFAs might reduce weight. 

PMID- 24891157
TI  - Multi-residue method for the determination of over 400 priority and emerging
      pollutants in water and wastewater by solid-phase extraction and liquid
      chromatography-time-of-flight mass spectrometry.
AB  - This article describes the development and validation of a liquid chromatography
      high-resolution mass spectrometry method for the simultaneous determination of
      over 400 multi-class priority and emerging pollutants with different
      physicochemical properties in environmental waters (surface water and
      wastewater). The proposed approach is based on the use of a database consisting
      of retention time/exact mass (of selected ions) pairs implemented with specific
      software for data analysis. The targeted list comprises 430 contaminants
      belonging to different compound categories, including 105 multiclass
      pharmaceuticals (analgesics/anti-inflammatories, antibiotics, lipid regulators,
      beta-blockers, antiepileptic/psychiatrics ulcer healings, diuretics, hormones and
      bronchodilatadors), life-style products (caffeine, nicotine), 21 drugs of abuse
      and their metabolites, 279 pesticides and some of their more relevant
      metabolites, nitrosamines, flame retardants, plasticizers and perfluorinated
      compounds. The proposed approach included a simple offline solid phase extraction
      (SPE) step using polymeric cartridges (Oasis HLB) with 200mL of water sample
      loaded, followed by analysis by rapid resolution liquid chromatography
      electrospray time-of-flight mass spectrometry (LC-TOFMS) in both positive and
      negative modes. The identification of the positive findings is accomplished with
      the data from accurate masses of the target ions along with retention time data
      and characteristic in-source fragment ions. The overall method performance was
      satisfactory with limits of quantification lower than 10ngL(-1) for the 44% of
      studied compounds. Recoveries between 50% and 130% were obtained for the 65% of
      the analytes (281 compounds). Matrix effects occurring with wastewater matrices
      were also assessed. The developed method was applied to the determination of
      target analytes in real surface water and wastewater samples. 

PMID- 24891156
TI  - Matched weight loss induced by sleeve gastrectomy or gastric bypass similarly
      improves metabolic function in obese subjects.
AB  - OBJECTIVE: The effects of marked weight loss, induced by Roux-en-Y gastric bypass
      (RYGB) or sleeve gastrectomy (SG) surgeries, on insulin sensitivity, beta-cell
      function and the metabolic response to a mixed meal were evaluated. METHODS:
      Fourteen nondiabetic insulin-resistant patients who were scheduled to undergo SG
      (n = 7) or RYGB (n = 7) procedures completed a hyperinsulinemic-euglycemic clamp
      procedure and a mixed-meal tolerance test before surgery and after losing ~20% of
      their initial body weight. RESULTS: Insulin sensitivity (insulin-stimulated
      glucose disposal during a clamp procedure), oral glucose tolerance (postprandial
      plasma glucose area under the curve), and beta-cell function (insulin secretion
      in relationship to insulin sensitivity) improved after weight loss, and were not
      different between surgical groups. The metabolic response to meal ingestion was
      similar after RYGB or SG, manifested by rapid delivery of ingested glucose into
      the systemic circulation and a large early postprandial increase in plasma
      glucose, insulin, and C-peptide concentrations in both groups. CONCLUSIONS: When
      matched on weight loss, RYGB and SG surgeries result in similar improvements in
      the two major factors involved in regulating plasma glucose homeostasis, insulin
      sensitivity and beta-cell function in obese people without diabetes.

PMID- 24891158
TI  - Isolation techniques for anthocyanidin 3,5-diglucosides and their related
      chemicals using supramolecules technique, and two solid-phase extraction
      cartridges.
AB  - Isolation techniques for anthocyanidin 3,5-diglucosides and their derivatives
      from three types of supramolecular pigments were newly developed using two SPE
      (Discovery DPA-6S and DSC-SCX) cartridges. Initially, malonylawobanin from
      commelinin supramolecular complex yielded 79.5% with 85.7% purity using DPA-6S,
      while DSC-SCX gave a rather lower yield (62.5%) of malonylawobanin with high
      purity (90.8%). Delphinidin 3,5-diglucoside and awobanin from acidic hydrolysis
      of commelinin were easily separated using DPA-6S. Secondary, artificial Perilla
      supramolecules (reconstructed from Perilla crude pigment, flavocommelin and
      Mg(2+)) result in a high purity of a malonylshisonin and shisonin mixture (96.1%)
      with DSC-SCX. Finally, succinylcyanin, which is a component of protocyanin,
      yielded 64.3% with 86.1% purity using DPA-6S and 51.8% with 74.1% purity using
      DSC-SCX. Moreover, cyanidin 3,5-diglucoside yielded 43.4% with 97.0% purity using
      DPA-6S after partial acidic hydrolysis of protocyanin. 

PMID- 24891159
TI  - Metal-organic framework UiO-66 coated stainless steel fiber for solid-phase
      microextraction of phenols in water samples.
AB  - Effective solid-phase microextraction (SPME) of polar phenols from water samples
      is usually difficult due to the strong interaction between polar phenols and
      aqueous matrix. Here, we report the fabrication of a metal-organic framework UiO
      66 coated stainless steel fiber via physical adhesion for the SPME of polar
      phenols (phenol, o-cresol, p-cresol, 2,6-dimethylphenol, 2,4-dichlorophenol and
      2,6-dichlorophenol) in water samples before gas chromatographic separation with
      flame ionic detection. Headspace SPME of 10mL sample solution with the fabricated
      UiO-66 coated fiber gave the enhancement factors of 160 (phenol) - 3769 (2,4
      dichlorophenol), and the linear ranges of 1-1000MUgL(-1) (2,6-dimethylphenol, 2,4
      dichlorophenol and 2,6-dichlorophenol), 1-500MUgL(-1) (o-cresol and p-cresol) and
      5-500MUgL(-1) (phenol). The detection limits ranged from 0.11MUgL(-1) (2,6
      dimethylphenol) to 1.23MUgL(-1) (phenol). The precision (relative standard
      deviations, RSDs) for six replicate determinations of the analytes at 100MUgL(-1)
      using a single UiO-66 coated fiber ranged from 2.8% to 6.2%. The fiber-to-fiber
      reproducibility (RSDs) for three parallel UiO-66 coated fibers varied from 5.9%
      to 10%. The recoveries obtained by spiking 5MUgL(-1) of the phenols in the water
      samples ranged from 80% to 115%. 

PMID- 24891160
TI  - Studies with an immobilized metal affinity chromatography cassette system
      involving binuclear triazacyclononane-derived ligands: automation of batch
      adsorption measurements with tagged recombinant proteins.
AB  - This study describes the determination of the adsorption isotherms and binding
      kinetics of tagged recombinant proteins using a recently developed IMAC cassette
      system and employing automated robotic liquid handling procedures for IMAC resin
      screening. These results confirm that these new IMAC resins, generated from a
      variety of different metal-charged binuclear 1,4,7-triaza-cyclononane (tacn)
      ligands, interact with recombinant proteins containing a novel N-terminal metal
      binding tag, NT1A, with static binding capacities similar to those obtained with
      conventional hexa-His tagged proteins, but with significantly increased
      association constants. In addition, higher kinetic binding rates were observed
      with these new IMAC systems, an attribute that can be positively exploited to
      increase process productivity. The results from this investigation demonstrate
      that enhancements in binding capacities and affinities were achieved with these
      new IMAC resins and chosen NT1A tagged protein. Further, differences in the
      binding performances of the bis(tacn) xylenyl-bridged ligands were consistent
      with the distance between the metal binding centres of the two tacn moieties, the
      flexibility of the ligand and the potential contribution from the aromatic ring
      of the xylenyl group to undergo pi/pi stacking interactions with the tagged
      proteins. 

PMID- 24891161
TI  - Optimisation of gradient elution with serially-coupled columns. Part I: single
      linear gradients.
AB  - A mixture of compounds often cannot be resolved with a single chromatographic
      column, but the analysis can be successful using columns of different nature,
      serially combined through zero-dead volume junctions. In previous work (JCA 1281
      (2013) 94), we developed an isocratic approach that optimised simultaneously the
      mobile phase composition, stationary phase nature and column length. In this
      work, we take the challenge of implementing optimal linear gradients for serial
      columns to decrease the analysis time for compounds covering a wide polarity
      range. For this purpose, five ACE columns of different selectivity (three C18
      columns of different characteristics, a cyano and a phenyl column) were combined,
      aimed to resolve a mixture of 15 sulphonamides using acetonitrile-water
      gradients. A gradient predictive system, based on numerical integration, was
      built to simulate chromatograms under linear gradient profiles. Two approaches
      were compared: the optimisation of the combination of columns pre-selecting the
      gradient profile, developed by De Beer et al. (Anal. Chem. 82 (2010) 1733), and
      the optimisation of the gradient program after pre-selecting the column
      combination using isocratic elution, developed for this work. Several refinements
      concerning the gradient delays along the solute migration and peak half-width
      modelling were included to improve the realism of the predictions. Pareto plots
      (expressed as analysis time versus predicted global resolution) assisted in the
      selection of the best separation conditions. The massive computation time in the
      gradient optimisation, once the column combination was optimised, was reduced to
      ca. 3min by using genetic algorithms. 

PMID- 24891162
TI  - A novel preparative liquid chromatograph for repetitive enrichment and
      purification of low-abundance compounds.
AB  - A novel recycle preparative HPLC system was developed to repeatedly enrich and
      purify low-abundance compounds from complex samples. The recycle separation
      involves injecting a large volume of the sample through a trap column, releasing
      the absorbed sample for preparative HPLC separation, and then capturing the
      target component in the same trap column for the next separation. After several
      cycles, the final purified target compound absorbed in the trap column is eluted
      with a small volume of solvent. The capture and recycle procedure was realized by
      adjusting the strength of the mobile phase using an auxiliary pump and switching
      the two valves connecting the trap and preparative columns. Compared with
      standard HPLC or existing recycle chromatography, this system not only reduces
      the solvent side-effects and sample volume overloading during injection but also
      avoids peak-broadening and sensitivity loss during the recycle runs. Moreover,
      the final purified products can be easily concentrated. With the aid of this
      system, a 10% polyphenol in extracts from Saussurea involucrata cultured cells
      reached >95% purity with more than 95% recovery after three recycle
      purifications, and a 1% unstable epimer impurity in the raw material of the drug
      silybin reached >95% purity with 75% recovery after a six-cycle separation. 

PMID- 24891163
TI  - Determination of dopamine, epinephrine, and norepinephrine by open-tubular
      capillary electrochromatography using graphene oxide molecularly imprinted
      polymers as the stationary phase.
AB  - A novel capillary electrochromatography method was developed for the
      determination of dopamine (DA), epinephrine (EP), and norepinephrine (NE) by
      using a graphene oxide (GO) molecularly imprinted polymers (MIPs) coated
      capillary. In this article, GO was introduced as supporting matrix to synthesize
      MIPs in the presence of DA as template molecule. Then GO MIPs were used as the
      stationary phase in electrochromatography for the determination of DA, EP, and
      NE. The separation of these three analytes was achieved under the optimal
      conditions with a satisfactory correlation coefficients (R(2) ) > 0.9957 in the
      range of 5.0-200.0 MUg/mL for EP and NE, and 20.0-200.0 MUg/mL for DA,
      respectively. The RSDs for the determination of three analytes were <6.19%, and
      the detection limits were 1.25 MUg/mL for EP and NE, and 10.0 MUg/mL for DA,
      respectively. Finally, this method was used for the determination of DA, EP, and
      NE in human serum and DA hydrochloride injection. 

PMID- 24891165
TI  - How to manage patients with differentiated thyroid cancer and a rising serum
      thyroglobulin level.
AB  - Serum thyroglobulin (sTg) is the marker for monitoring persistence/recurrence of
      differentiated thyroid cancer, in patients without sTg antibodies. Patients with
      undetectable basal sTg or peak sTg <2 ng/mL are cured with low risk to recur.
      Newly detectable level of sTg indicates the recurrence. The significance of
      increasing sTg in patients treated with emithyroidectomy or total-thyroidectomy
      but not ablated with radioiodine is undefined. A doubling time <1 year may be a
      poor prognostic factor, but this is more relevant in cases with high levels of
      sTg. Because of its sensitivity, neck ultrasound should be performed at any
      visit, especially when an increased sTg is seen. 

PMID- 24891164
TI  - Gibberellin biosynthesis and signal transduction is essential for internode
      elongation in deepwater rice.
AB  - Under flooded conditions, the leaves and internodes of deepwater rice can
      elongate above the water surface to capture oxygen and prevent drowning. Our
      previous studies showed that three major quantitative trait loci (QTL) regulate
      deepwater-dependent internode elongation in deepwater rice. In this study, we
      investigated the age-dependent internode elongation in deepwater rice. We also
      investigated the relationship between deepwater-dependent internode elongation
      and the phytohormone gibberellin (GA) by physiological and genetic approach using
      a QTL pyramiding line (NIL-1 + 3 + 12). Deepwater rice did not show internode
      elongation before the sixth leaf stage under deepwater condition. Additionally,
      deepwater-dependent internode elongation occurred on the sixth and seventh
      internodes during the sixth leaf stage. These results indicate that deepwater
      rice could not start internode elongation until the sixth leaf stage. Ultra
      performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) method
      for the phytohormone contents showed a deepwater-dependent GA1 and GA4
      accumulation in deepwater rice. Additionally, a GA inhibitor abolished deepwater
      dependent internode elongation in deepwater rice. On the contrary, GA feeding
      mimicked internode elongation under ordinary growth conditions. However,
      mutations in GA biosynthesis and signal transduction genes blocked deepwater
      dependent internode elongation. These data suggested that GA biosynthesis and
      signal transduction are essential for deepwater-dependent internode elongation in
      deepwater rice. 

PMID- 24891166
TI  - Molecular diagnostics for thyroid nodules: the current state of affairs.
AB  - Molecular diagnostics offers great promise for the evaluation of cytologically
      indeterminate thyroid nodules. Numerous molecular genetic and immunohistochemical
      tests have been developed that may be performed on thyroid specimens obtained
      during standard fine-needle aspiration, some of which may greatly improve
      diagnostic yield. A sound understanding of the diagnostic performance of these
      tests, and how they can enhance clinical practice, is important. This article
      reviews the diagnostic utility of immunohistochemical and molecular testing for
      the clinical assessment of thyroid nodules, and makes recommendations about how
      these tests can be integrated into clinical practice for patients with
      cytologically indeterminate thyroid nodules. 

PMID- 24891167
TI  - Thyrotropin in the development and management of differentiated thyroid cancer.
AB  - Thyrotropin (TSH) is the major regulator and growth factor of the thyroid. TSH
      may be important in the development of human thyroid cancer, with both suggestive
      animal models and clinical evidence, although definitive proof is still required.
      Applications for TSH in thyroid cancer management include TSH stimulation of
      radioiodine uptake, enhancement of biochemical monitoring through thyroglobulin
      measurement, and long-term suppression of TSH with supraphysiologic
      levothyroxine. This review synthesizes current knowledge of TSH in both the
      development and management of differentiated thyroid cancer. 

PMID- 24891168
TI  - Initial radioiodine administration: when to use it and how to select the dose.
AB  - All published guidelines on the use of radioactive iodine for the treatment of
      well-differentiated thyroid cancer agree that an individualized assessment of the
      risk of cancer-related mortality and of disease recurrence should direct the
      decision of whether radioiodine treatment is needed and how much to administer.
      At the author's institution, they mostly follow the American Thyroid
      Association's risk stratification system, with the addition of a category of very
      low-risk patients that do not receive radioactive iodine. 

PMID- 24891169
TI  - Update on differentiated thyroid cancer staging.
AB  - In this review, we demonstrate how initial estimates of the risk of disease
      specific mortality and recurrent/persistent disease should be used to guide
      initial treatment recommendations and early management decisions and to set
      appropriate patient expectations with regard to likely outcomes after initial
      therapy of thyroid cancer. The use of ongoing risk stratification to modify these
      initial risk estimates is also discussed. Novel response to therapy definitions
      are proposed that can be used for ongoing risk stratification in thyroid cancer
      patients treated with lobectomy or total thyroidectomy without radioactive iodine
      remnant ablation. 

PMID- 24891170
TI  - Update on medullary thyroid cancer.
AB  - Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer, demonstrating
      variable behavior from indolent disease to highly aggressive, progressive
      disease. There are distinguishing phenotypic features of sporadic and hereditary
      MTC. Activation or overexpression of cell surface receptors and up-regulation of
      intracellular signaling pathways in hereditary and sporadic MTC are involved in
      the disease pathogenesis. There has been an exponential rise in clinical trials
      with investigational agents, leading to approval of 2 medications for
      progressive, advanced MTC. Developments in understanding the pathogenesis of MTC
      will hopefully lead to more effective and less toxic treatments of this rare but
      difficult to treat cancer. 

PMID- 24891171
TI  - Surgery for thyroid cancer.
AB  - The incidence of thyroid cancer, particularly papillary thyroid cancer, is rising
      at an epidemic rate. The mainstay of treatment of most patients with thyroid
      cancer is surgery. Considerable controversy exists about the extent of thyroid
      surgery and lymph node resection in patients with thyroid cancer. Surgical
      experience in judgment and technique is required to achieve optimal patient
      outcomes. 

PMID- 24891172
TI  - Alternative approaches to the thyroid gland.
AB  - Advances in surgical technology and patient-driven demands have fueled
      exploration into methods to improve cosmetic outcomes in thyroid surgery. This
      exploration has produced 2 fundamentally different pathways for reducing the
      visible thyroidectomy scar. Minimally invasive anterior cervical approaches use
      small incisions hidden in natural skin creases and reduce the overall extent of
      dissection required to remove the thyroid. Remote access approaches remove the
      incision from the anterior neck completely but require more extensive dissection
      to access the thyroid compartment. 

PMID- 24891174
TI  - Management of Graves' disease: an overview and comparison of clinical practice
      guidelines with actual practice trends.
AB  - Over the last century, much has been learned about the pathogenesis,
      manifestations, and management of Graves' disease leading to the establishment of
      evidence-based clinical practice guidelines. The joint clinical practice
      guidelines from the American Thyroid Association and the American Association of
      Clinical Endocrinologists give recommendations on both the diagnosis and
      treatment of hyperthyroidism. A survey of clinicians performed that same year,
      however, revealed that current practices diverge from these recently published
      guidelines in multiple areas. These differences will need to be assessed serially
      to determine the impact of the guidelines on future clinical practice and perhaps
      vice versa. 

PMID- 24891173
TI  - Persistent posttreatment fatigue in thyroid cancer survivors: a scoping review.
AB  - The relevance of persistent posttreatment fatigue (PPF) to thyroid cancer (TC)
      survivor populations is not known. This article presents a scoping review, which
      is an overview of published research activity. Uncontrolled data suggest that PPF
      is one of the most common complaints in TC survivors. Furthermore, statistically
      significantly worse levels of fatigue were reported in TC survivors, compared
      with the general population or healthy controls. There was some inconsistency
      among PPF risk factors. More research is needed on PPF in TC survivors, including
      long-term prospective cohort studies, research on fatigue severity prevalence,
      and randomized controlled trials of treatment strategies. 

PMID- 24891175
TI  - Thyroid disease and the cardiovascular system.
AB  - Thyroid hormones, specifically triiodothyronine (T3), have significant effects on
      the heart and cardiovascular system. Hypothyroidism, hyperthyroidism, subclinical
      thyroid disease, and low T3 syndrome each cause cardiac and cardiovascular
      abnormalities through both genomic and nongenomic effects on cardiac myocytes and
      vascular smooth muscle cells. In compromised health, such as occurs in heart
      disease, alterations in thyroid hormone metabolism may further impair cardiac and
      cardiovascular function. Diagnosis and treatment of cardiac disease may benefit
      from including analysis of thyroid hormone status, including serum total T3
      levels. 

PMID- 24891176
TI  - Thyroid disease and cognition.
AB  - Overt hypothyroidism and thyrotoxicosis are associated with significant
      decrements in mood and cognitive function, and therapy usually leads to
      improvement in these symptoms. In contrast, major affective or cognitive
      dysfunction is not typical of subclinical thyroid disease. Subtle deficits in
      specific cognitive domains (primarily working memory and executive function)
      likely exist in subclinical hypothyroidism and thyrotoxicosis, but these are
      unlikely to cause major problems in most patients. Patients with mild thyroid
      disease and significant distress related to mood or cognition most likely have
      independent diagnoses that should be evaluated and treated separately. 

PMID- 24891177
TI  - Ethical issues in the management of thyroid disease.
AB  - The focus of this article is on clinical ethics issues in the thyroid disease
      context. Clinical ethics is a subspecialty of bioethics that deals with bedside
      ethical dilemmas that specifically involve the provider-patient relationship.
      Such issues include consent and capacity; weighing therapeutic benefits against
      risks and side-effects; innovative therapies; end of life care; unintended versus
      intentional harms to patients or patient populations; and healthcare access. This
      article will review core ethical principles for practice, as well as the moral
      and legal requirements of informed consent. It will then discuss the range of
      unique and universal ethical issues and considerations that present in the
      management of autoimmune thyroid disease and thyroid cancer. 

PMID- 24891178
TI  - Management of recurrent cervical papillary thyroid cancer.
AB  - Papillary thyroid cancer is one of the most common endocrine malignancies, and it
      is often associated with an excellent prognosis. However, it has been shown to
      recur in the lymph nodes in the neck. The management of these lymph nodes remains
      controversial, and current treatment strategies include observation, surgery,
      radioactive iodine ablation, and percutaneous ethanol injection. These various
      treatment modalities are discussed in this article. 

PMID- 24891179
TI  - Thyroid disorders during pregnancy.
AB  - Thyroid disorders are common in pregnancy and in nonpregnant women of
      childbearing age, but can be missed because of nonspecific symptoms and normal
      changes in thyroid gland physiology during pregnancy. The prevalence of overt
      hyperthyroidism complicating pregnancy has been reported to range between 0.4%
      and 1.7%, and an estimated 2% to 3% of women are hypothyroid during pregnancy.
      Abnormalities in maternal thyroid function are associated with complications
      during pregnancy, and may affect maternal and fetal outcomes. Thus it is
      important to identify thyroid disorders before pregnancy or early in pregnancy so
      that appropriate treatment can be initiated. 

PMID- 24891180
TI  - Thyroid cancer and other thyroid disorders.

PMID- 24891181
TI  - Thyroid cancer and other thyroid disorders.

PMID- 24891182
TI  - Functional response to cardiac resynchronization therapy in patients with renal
      dysfunction and subsequent long-term mortality.
AB  - INTRODUCTION: Renal dysfunction is associated with increased morbi-mortality in
      heart failure patients. Data regarding functional and clinical efficacy of
      cardiac resynchronization therapy (CRT) in this population are limited. METHODS
      AND RESULTS: We aimed to evaluate the rate of functional response to CRT in
      patients with renal dysfunction and its association with long-term mortality. Our
      study included a total of 179 consecutive patients implanted between 2007 and
      2010. The rate of functional response to CRT (defined by a composite score using
      New York Heart Association functional class, 6-minute walk test, and quality of
      life) was compared between patients with and without renal dysfunction (defined
      as eGFR < or >=60 mL/min/1.73 m(2) ). Survival analysis estimates were
      constructed according to the Kaplan-Meier method, with results comparison using
      the log-rank test. During a median follow-up of 4.2 years, 73 patients (40%)
      died. Patients with low eGFR were older (72 +/- 8 years vs. 64 +/- 12 years; P <
      0.001), and had higher prevalence of ischemic heart disease (75% vs. 53%; P =
      0.003). Functional response rates did not differ significantly between patients
      with and without renal dysfunction (58% and 69%, respectively; P = 0.14). Despite
      overall higher mortality in patients with low eGFR (53.8% vs. 22.7%; P < 0.001),
      the presence of functional response at 1 year among patients with renal
      dysfunction was still independently associated with an improved long-term
      survival (HR = 0.49 [95%CI: 0.28-0.83]; P = 0.009). CONCLUSION: Functional
      response to CRT at 1 year does not differ significantly between patients with or
      without kidney disease, and is an independent predictor of improved long-term
      survival in patients with renal dysfunction.

PMID- 24891184
TI  - Abstracts of the 38th Annual Congress of the Italian Urodynamic Society, 19-21
      June, 2014, Milan, Italy.

PMID- 24891183
TI  - COL1A1 C-propeptide cleavage site mutation causes high bone mass, bone fragility
      and jaw lesions: a new cause of gnathodiaphyseal dysplasia?
AB  - Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant condition
      characterized by bone fragility, irregular bone mineral density (BMD) and fibro
      osseous lesions in the skull and jaw. Mutations in Anoctamin-5 (ANO5) have been
      identified in some cases. We aimed to identify the causative mutation in a family
      with features of GDD but no mutation in ANO5, using whole exome capture and
      massive parallel sequencing (WES). WES of two affected individuals (a mother and
      son) and the mother's unaffected parents identified a mutation in the C
      propeptide cleavage site of COL1A1. Similar mutations have been reported in
      individuals with osteogenesis imperfecta (OI) and paradoxically increased BMD. C
      propeptide cleavage site mutations in COL1A1 may not only cause 'high bone mass
      OI', but also the clinical features of GDD, specifically irregular sclerotic BMD
      and fibro-osseous lesions in the skull and jaw. GDD patients negative for ANO5
      mutations should be assessed for mutations in type I collagen C-propeptide
      cleavage sites. 

PMID- 24891185
TI  - De novo deletion of TBL1XR1 in a child with non-specific developmental delay
      supports its implication in intellectual disability.
AB  - We report on a 6-year-old child with a de novo 1.6 Mb deletion in the
      3q26.31q26.32 region identified by SNP array, involving only one relevant gene:
      TBL1XR1. The girl shows non-specific, mild to moderate intellectual deficiency
      but no autistic behavior. Point mutations in TBL1XR1 have recently been
      implicated in three patients with intellectual disability (ID) and autistic
      features. Our report supports that haploinsufficiency for TBL1XR1 could be
      implicated in non-ASD autosomal dominant ID.

PMID- 24891187
TI  - MiR-195 targets HDGF to inhibit proliferation and invasion of NSCLC cells.
AB  - Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer
      related death worldwide. MicroRNAs (miRNAs) play critical roles in the
      development and progression of NSCLC. miR-195 acts as a tumor suppressor in
      several cancers, however, its role in NSCLC is not well understood. Herein, we
      found that miR-195 was significantly decreased in both NSCLC tissues and cell
      lines. Forced expression of miR-195 significantly suppressed proliferation,
      migration, and invasion of NSCLC cells. Hepatoma-derived growth factor (HDGF) was
      identified as a target of miR-195 in NSCLC cells. Overexpression of HDGF
      dramatically abolished the tumor suppressive role of miR-195 in NSCLC cells. Our
      results demonstrated a tumor suppressive role of miR-195 in NSCLC, and suggested
      a potential therapeutic target for NSCLC.

PMID- 24891186
TI  - The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion
      molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast
      cancer.
AB  - The purpose of this study was to determine the clinical significance of vascular
      cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM)
      in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex
      matched healthy controls were enrolled into this study. Pretreatment serum
      markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent
      assay (ELISA)). The median age at diagnosis was 48 years (range 29-80 years).
      Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic
      disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %)
      patients died during follow-up. Median progression-free survival (PFS) and
      overall survival (OS) were 8.6 +/- 1.7 and 35.5 +/- 1.5 months, respectively. The
      baseline serum EpCAM levels of the patients were significantly higher than those
      of the controls (p < 0.001). There was no significant difference in the serum
      levels of VCAM-1 between the patients and controls (p = 0.47). No significant
      correlation was detected between the levels of the serum markers and other
      clinical parameters (p > 0.05). Patients with HER-2-positive and triple-negative
      tumors had significantly poorer PFS (p = 0.04 and p = 0.001, respectively), while
      metastatic disease and chemotherapy unresponsiveness had significantly adverse
      effect on OS analysis (p < 0.001 and p < 0.001, respectively). Neither serum VCAM
      1 levels nor serum EpCAM levels were identified to have a prognostic role on
      either PFS or OS (VCAM-1 p = 0.76 and p = 0.32; EpCAM p = 0.16 and p = 0.69,
      respectively). Even though any predictive or prognostic role could not be
      determined for both markers, serum levels of EpCAM were found to have diagnostic
      value in BC patients.

PMID- 24891188
TI  - Comparison of ERCP, EUS, and ERCP combined with EUS in diagnosing pancreatic
      neoplasms: a systematic review and meta-analysis.
AB  - In the current study, we performed a systematic review of literature pertaining
      to the diagnostic value of endoscopic retrograde cholangiopancreatography (ERCP),
      endoscopic ultrasonography (EUS), and combined ERCP plus EUS to pancreatic
      cancer. We searched MEDLINE, OVID, and the Cochrane Library for studies
      evaluating diagnostic validity of ERCP, EUS, and ERCP plus EUS between January
      1989 and May 2014. We obtained pooled estimates of sensitivity, specificity, and
      summary receiver operating characteristic curves (SROC). A total of 10 studies
      that included 669 patients who fulfilled all of the inclusion criteria were
      considered for inclusion in the analysis. The pooled sensitivities of EUS, ERCP,
      and EUS plus ERCP were 76.7, 57.9, and 79.9 %, respectively. The pooled
      specificities were 91.7, 90.6, and 94.2 %, respectively. The *Q index estimates
      were 0.828, 0.862, and 0.896, respectively. The *Q indices for EUS and EUS plus
      ERCP were significantly higher compared with ERCP (P = 0.010 and 0.008,
      respectively). Our meta-analysis showed that ERCP plus EUS was associated with a
      high diagnostic value for the detection of pancreatic neoplasms compared with
      ERCP and EUS alone.

PMID- 24891189
TI  - A dominant mutation in tyrp1A leads to melanophore death in zebrafish.
AB  - Melanin biosynthesis in vertebrates depends on the function of three enzymes of
      the tyrosinase family, tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1),
      and dopachrome tautomerase (Dct or Tyrp2). Tyrp1 might play an additional role in
      the survival and proliferation of melanocytes. Here, we describe a mutation in
      tyrp1A, one of the two tyrp1 paralogs in zebrafish, which causes melanophore
      death leading to a semi-dominant phenotype. The mutation, an Arg->Cys change in
      the amino-terminal part of the protein, is similar to mutations in humans and
      mice where they lead to blond hair (in melanesians) or dark hair with white
      bases, respectively. We demonstrate that the phenotype in zebrafish depends on
      the presence of the mutant protein and on melanin synthesis. Ultrastructural
      analysis shows that the melanosome morphology and pigment content are altered in
      the mutants. These structural changes might be the underlying cause for the
      observed cell death, which, surprisingly, does not result in patterning defects. 

PMID- 24891190
TI  - Base-controlled selectivity in the synthesis of linear and angular fused
      quinazolinones by a palladium-catalyzed carbonylation/nucleophilic aromatic
      substitution sequence.
AB  - A new approach for the facile synthesis of fused quinazolinone scaffolds through
      a palladium-catalyzed carbonylative coupling followed by an intramolecular
      nucleophilic aromatic substitution is described. The base serves as the key
      modulator: Whereas DBU gives rise to the linear isomers, Et3N promotes the
      preferential formation of angular products. Interestingly, a light-induced 4+4
      reaction of the product was also observed.

PMID- 24891191
TI  - Posthumous Organ Retention and Use in Ghana: Regulating Individual, Familial and
      Societal Interests.
AB  - The question of whether individuals retain interests or can be harmed after death
      is highly contentious, particularly within the context of deceased organ
      retrieval, retention and use. This paper argues that posthumous interests and/or
      harms can and do exist in the Konkomba (and wider Ghanaian) traditional setting
      through the concept of ancestorship, a reputational concept of immense cultural
      and existential significance in this setting. I adopt Joel Feinberg's account of
      harms as a setback to interests. The paper argues that a socio-culturally
      sensitive regulatory framework does not necessarily exclude the donation of
      (deceased) human biomaterials for transplant and science research. Indeed, when
      customary values are explored with open-mindedness and sensitivity it may be
      shown that such donation can form part of the important customs of some
      communities in this jurisdiction. Accordingly, a context-appropriate governance
      framework could utilise the cultural value of ancestorship as an incentive to
      encourage organ donation in the Ghanaian traditional setting.

PMID- 24891193
TI  - Approaches to manual ventilation.
AB  - Manual ventilation is a basic skill that involves airway assessment, maneuvers to
      open the airway, and application of simple and complex airway support devices and
      effective positive-pressure ventilation using a bag and mask. An important part
      of manual ventilation is recognizing its success and when it is difficult or
      impossible and a higher level of support is necessary to sustain life. Careful
      airway assessment will help clinicians identify what and when the next step needs
      to be taken. Often simple airway maneuvers such as the head tilt/chin lift and
      jaw thrust can achieve a patent airway. Appropriate use of airway adjuncts can
      further aid the clinician in situations in which airway maneuvers may not be
      sufficient. Bag-mask ventilation (BMV) plays a vital role in effective manual
      ventilation, improving both oxygenation and ventilation as well as buying time
      while preparations are made for endotracheal intubation. There are, however,
      situations in which BMV may be difficult or impossible. Anticipation and early
      recognition of these situations allows clinicians to quickly make adjustments to
      the method of BMV or to employ a more advanced intervention to avoid delays in
      establishing adequate oxygenation and ventilation. 

PMID- 24891194
TI  - Elective intubation.
AB  - Endotracheal intubation is a commonly performed operating room (OR) procedure
      that provides safe delivery of anesthetic gases and airway protection during
      surgery. The most common intubation technique in the perioperative environment is
      direct laryngoscopy with orotracheal tube insertion. Infrequently, difficulties
      that require an alternative intubation technique are encountered due to patient
      anatomy, equipment limitations, or patient pathophysiology. Careful patient
      evaluation, advanced planning, equipment preparation, system redundancy, use of
      checklists, familiarity with airway algorithms, and availability of additional
      help when needed during OR intubations have resulted in exceptional success and
      safety. Airway difficulties during intubation outside the controlled environment
      of the OR are more frequent and more serious. Translating the intubation
      processes practiced in the OR to intubations outside the perioperative setting
      should improve patient safety. This paper considers each step in the OR
      intubation process in detail and proposes ways of incorporating perioperative
      procedures into intubations outside the OR. Management of the physiologic impact
      of intubation, lack of readily available specialized equipment and experienced
      help, and planning for transfer of care following intubation are all challenges
      during these intubations. 

PMID- 24891195
TI  - Direct and indirect laryngoscopy: equipment and techniques.
AB  - Visualization of the larynx by direct or indirect means is referred to as
      laryngoscopy and is the principal aim during airway management for passage of a
      tracheal tube. This paper presents a brief background regarding the development
      and practice of laryngoscopy and examines the equipment and techniques for both
      direct and indirect methods. Patient evaluation during the airway examination is
      discussed, as are predictors for difficult intubation. Laryngoscope blade design,
      newer intubating techniques, and a variety of indirect laryngoscopic technologies
      are reviewed, as is the learning curve for these techniques and devices. 

PMID- 24891196
TI  - Fiberoptic intubation: an overview and update.
AB  - Fiberoptic intubation (FOI) is an effective technique for establishing airway
      access in patients with both anticipated and unanticipated difficult airways.
      First described in the late 1960s, this approach can facilitate airway management
      in a variety of clinical scenarios given proper patient preparation and
      technique. This paper seeks to review the pertinent technology, clinical
      techniques, and indications for and complications of its use. The role of FOI in
      airway management algorithms is discussed. Evidence is presented comparing FOI to
      other techniques with regard to difficult airway management. In addition, we have
      reviewed the literature on training processes and skill development in FOI. 

PMID- 24891197
TI  - Emergency tracheal intubation: techniques and outcomes.
AB  - Performing emergency endotracheal intubation necessarily means doing so under
      less than ideal conditions. Rates of first-time success will be lower than
      endotracheal intubation performed under controlled conditions in the operating
      room. Some factors associated with improved success are predictable and can be
      modified to improve outcome. Factors to be discussed include the initial decision
      to perform endotracheal intubation in out-of-hospital settings, qualifications
      and training of providers performing intubation, the technique selected for
      advanced airway management, and the use of sedatives and neuromuscular blocking
      agents. 

PMID- 24891198
TI  - Tracheostomy: epidemiology, indications, timing, technique, and outcomes.
AB  - Tracheostomy is a common procedure performed in critically ill patients requiring
      prolonged mechanical ventilation for acute respiratory failure and for airway
      issues. The ideal timing (early vs late) and techniques (percutaneous
      dilatational, other new percutaneous techniques, open surgical) for tracheostomy
      have been topics of considerable debate. In this review, we address general
      issues regarding tracheostomy (epidemiology, indications, and outcomes) and
      specifically review the literature regarding appropriate timing of tracheostomy
      tube placement. Based on evidence from 2 recent large randomized trials, it is
      reasonable to wait at least 10 d to be certain that a patient has an ongoing need
      for mechanical ventilation before consideration of tracheostomy. Percutaneous
      tracheostomy with flexible bronchoscopy guidance is recommended, and optimal
      percutaneous techniques, indications, and contraindications and results in high
      risk patients (coagulopathy, thrombocytopenia, obesity) are reviewed. Additional
      issues related to tracheostomy diagnosis-related groups, charges, and procedural
      costs are reviewed. New advances regarding tracheostomy include the use of real
      time ultrasound guidance for percutaneous tracheostomy in high-risk patients. New
      tracheostomy tubes (tapered with low-profile cuffs that fit better on the tapered
      dilators, longer percutaneous tracheostomy tubes) are discussed for optimal use
      with percutaneous dilatational tracheostomy. Two new percutaneous techniques, a
      balloon inflation technique (Dolphin) and the PercuTwist procedure, are reviewed.
      The efficacy of tracheostomy teams and tracheostomy hospital services with
      standardized protocols for tracheostomy insertion and care has been associated
      with improved outcomes. Finally, the UK National Tracheostomy Safety Project
      developed standardized resources for education of both health care providers and
      patients, including emergency algorithms for tracheostomy incidents, and serves
      as an excellent educational resource in this important area. 

PMID- 24891199
TI  - Supraglottic airway devices.
AB  - Supraglottic airway devices (SADs) are used to keep the upper airway open to
      provide unobstructed ventilation. Early (first-generation) SADs rapidly replaced
      endotracheal intubation and face masks in > 40% of general anesthesia cases due
      to their versatility and ease of use. Second-generation devices have further
      improved efficacy and utility by incorporating design changes. Individual second
      generation SADs have allowed more dependable positive-pressure ventilation, are
      made of disposable materials, have integrated bite blocks, are better able to act
      as conduits for tracheal tube placement, and have reduced risk of pulmonary
      aspiration of gastric contents. SADs now provide successful rescue ventilation in
      > 90% of patients in whom mask ventilation or tracheal intubation is found to be
      impossible. However, some concerns with these devices remain, including failing
      to adequately ventilate, causing airway damage, and increasing the likelihood of
      pulmonary aspiration of gastric contents. Careful patient selection and excellent
      technical skills are necessary for successful use of these devices. 

PMID- 24891200
TI  - Endotracheal tubes: old and new.
AB  - The development and evolution of the endotracheal tube (ETT) have been closely
      related to advances in surgery and anesthesia. Modifications were made to
      accomplish many tasks, including minimizing gross aspiration, isolating a lung,
      providing a clear facial surgical field during general anesthesia, monitoring
      laryngeal nerve damage during surgery, preventing airway fires during laser
      surgery, and administering medications. In critical care management, ventilator
      associated pneumonia (VAP) is a major concern, as it is associated with increased
      morbidity, mortality, and cost. It is increasingly appreciated that the ETT
      itself is a primary causative risk for developing VAP. Unfortunately,
      contaminated oral and gastric secretions leak down past the inflated ETT cuff
      into the lung. Bacteria can also grow within the ETT in biofilm and re-enter the
      lung. Modifications to the ETT that attempt to prevent bacteria from entering
      around the ETT include maintaining an adequate cuff pressure against the tracheal
      wall, changing the material and shape of the cuff, and aspirating the secretions
      that sit above the cuff. Attempts to reduce bacterial entry through the tube
      include antimicrobial coating of the ETT and mechanically scraping the biofilm
      from within the ETT. Studies evaluating the effectiveness of these modifications
      and techniques demonstrate mixed results, and clear recommendations for which
      modification should be implemented are weak. 

PMID- 24891201
TI  - Tracheostomy tubes.
AB  - Tracheostomy tubes are used to administer positive-pressure ventilation, to
      provide a patent airway, and to provide access to the lower respiratory tract for
      airway clearance. They are available in a variety of sizes and styles from
      several manufacturers. The dimensions of tracheostomy tubes are given by their
      inner diameter, outer diameter, length, and curvature. Differences in dimensions
      between tubes with the same inner diameter from different manufacturers are not
      commonly appreciated but may have important clinical implications. Tracheostomy
      tubes can be cuffed or uncuffed and may be fenestrated. Some tracheostomy tubes
      are designed with an inner cannula. It is important for clinicians caring for
      patients with a tracheostomy tube to appreciate the nuances of various
      tracheostomy tube designs and to select a tube that appropriately fits the
      patient. The optimal frequency of changing a chronic tracheostomy tube is
      controversial. Specialized teams may be useful in managing patients with a
      tracheostomy. Speech can be facilitated with a speaking valve in patients with a
      tracheostomy tube who are breathing spontaneously. In mechanically ventilated
      patients with a tracheostomy, a talking tracheostomy tube, a deflated cuff
      technique with a speaking valve, or a deflated cuff technique without a speaking
      valve can be used to facilitate speech. 

PMID- 24891202
TI  - Management of the artificial airway.
AB  - Management of the artificial airway includes securing the tube to prevent
      dislodgement or migration as well as removal of secretions. Preventive measures
      include adequate humidification and appropriate airway suctioning. Monitoring
      airway patency and removing obstruction are potentially life-saving components of
      airway management. Cuff pressure management is important for preventing
      aspiration and mucosal damage as well as assuring adequate ventilation. A number
      of new monitoring techniques have been introduced, and automated cuff pressure
      control is becoming more common. The respiratory therapist should be adept with
      all these devices and understand the appropriate application and management. 

PMID- 24891203
TI  - Tracheal extubation.
AB  - Tracheal extubation in both the critical care and anesthesia setting is not only
      an important milestone for patient recovery, but also a procedure that carries a
      considerable risk of complication or failure. Mechanical ventilation is
      associated with significant complications that are time-dependent in nature, with
      a longer duration of intubation resulting in a higher incidence of complications,
      including ventilator-associated pneumonia, and increased mortality. Extubation
      failure and subsequent re-intubation are associated with an overall increase in
      the duration of mechanical ventilation, increased mortality, a greater need for
      tracheostomy, and higher medical costs. These risks demand that the process of
      extubation be managed by practitioners with a detailed understanding of the
      causes of extubation failure and the potential complications. A pre-established
      extubation plan with considerations made for the possible need for re-intubation
      is of the utmost importance. 

PMID- 24891204
TI  - Complications of airway management.
AB  - Although endotracheal intubation is commonly performed in the hospital setting,
      it is not without risk. In this article, we review the impact of endotracheal
      intubation on airway injury by describing the acute and long-term sequelae of
      each of the most commonly injured anatomic sites along the respiratory tract,
      including the nasal cavity, oral cavity, oropharynx, larynx, and trachea.
      Injuries covered include nasoseptal injury, tongue injury, dental injury, mucosal
      lacerations, vocal cord immobility, and laryngotracheal stenosis, as well as
      tracheomalacia, tracheoinnominate, and tracheoesophageal fistulas. We discuss the
      proposed mechanisms of tissue damage that relate to each and present their most
      common clinical manifestations, along with their respective diagnostic and
      management options. This article also includes a review of complications of
      airway management pertaining to video laryngoscopy and supraglottic airway
      devices. Finally, potential strategies to prevent intubation-associated injuries
      are outlined. 

PMID- 24891205
TI  - Development of novel selective peptidomimetics containing a boronic acid moiety,
      targeting the 20S proteasome as anticancer agents.
AB  - This paper describes the design, synthesis, and biological evaluation of
      peptidomimetic boronates as inhibitors of the 20S proteasome, a validated target
      in the treatment of multiple myeloma. The synthesized compounds showed a good
      inhibitory profile against the ChT-L activity of 20S proteasome. Compounds
      bearing a beta-alanine residue at the P2 position were the most active, that is,
      3-ethylphenylamino and 4-methoxyphenylamino (R)-1-{3-[4-(substituted)-2
      oxopyridin-1(2H)-yl]propanamido}-3-methylbutylboronic acids (3 c and 3 d,
      respectively), and these derivatives showed inhibition constants (Ki ) of 17 and
      20 nM, respectively. In addition, they co-inhibited post glutamyl peptide
      hydrolase activity (3 c, Ki=2.57 MUM; 3 d, Ki=3.81 MUM). No inhibition was
      recorded against the bovine pancreatic alpha-chymotrypsin, which thus confirms
      the selectivity towards the target enzyme. Docking studies of 3 c and related
      inhibitors into the yeast proteasome revealed the structural basis for
      specificity. The evaluation of growth inhibitory effects against 60 human tumor
      cell lines was performed at the US National Cancer Institute. Among the selected
      compounds, 3 c showed 50% growth inhibition (GI50) values at the sub-micromolar
      level on all cell lines.

PMID- 24891207
TI  - Surgical outcomes in the elderly patient after osteocutaneous free flap transfer.
AB  - OBJECTIVES/HYPOTHESIS: Morbidity of free tissue transfer in the elderly patient
      is controversial. Recent studies have shown no significant difference in elderly
      fasciocutaneous free-flap donor site morbidity. The purpose of this study is to
      assess surgical outcomes in elderly patients receiving osteocutaneous free-tissue
      transfer. STUDY DESIGN: Retrospective chart review of patients 70 years and older
      undergoing osteocutaneous free flaps from 2000 to 2013. METHODS: Fibular, radial
      forearm, and scapular flaps were reviewed. Younger patients randomly selected
      from the same time period served as controls. Data collected included donor site
      morbidity, flap complications, feeding tube and tracheostomy dependence, and
      hospital stay. RESULTS: Forty-four osteocutaneous free flaps were performed in
      elderly patients. Overall, there was no significant difference in donor site
      morbidity between older and younger patients (P = 0.50) (tendon exposure, P =
      1.00; split-thickness skin graft loss, P = 0.36; infections, P = 0.52;
      dehiscence, P = 1.00; and seroma, P = 1.00). There was no significant difference
      between older and younger patients being decannulated (P = 0.61) or the time to
      decannulation (P = 0.24). There was no difference in those who returned to
      baseline diet (P = 0.67). All patients returned to baseline ambulatory and
      shoulder status. Length of postoperative hospitalization (P = 0.78) and intensive
      care unit stay (P = 0.94) were also equal. The only significant difference was
      that more elderly patients were discharged to skilled nursing facilities (SNF)
      (40.9% vs. 15.9%, P < 0.01). CONCLUSION: Elderly patients undergoing free tissue
      transfer have similar flap and donor site outcomes, feeding tube and tracheostomy
      outcomes, ambulatory status, and hospital stays compared to younger patients.
      They are, however, more likely to require SNF care posthospitalization. LEVEL OF
      EVIDENCE: 4.

PMID- 24891208
TI  - Nodular papillomatosis in a 12-year-old female.

PMID- 24891206
TI  - miR-155 deficiency protects mice from experimental colitis by reducing T helper
      type 1/type 17 responses.
AB  - Inflammatory bowel disease (IBD), a chronic intestinal inflammatory condition
      that affects millions of people worldwide, results in high morbidity and
      exorbitant health-care costs. The critical features of both innate and adaptive
      immunity are to control inflammation and dysfunction in this equilibrium is
      believed to be the reason for the development of IBD. miR-155, a microRNA, is up
      regulated in various inflammatory disease states, including IBD, and is a
      positive regulator of T-cell responses. To date, no reports have defined a
      function for miR-155 with regard to cellular responses in IBD. Using an acute
      experimental colitis model, we found that miR-155(-/-) mice, as compared to wild
      type control mice, have decreased clinical scores, a reversal of colitis
      associated pathogenesis, and reduced systemic and mucosal inflammatory cytokines.
      The increased frequency of CD4+ lymphocytes in the spleen and lamina propria with
      dextran sodium sulphate induction was decreased in miR-155(-/-) mice. Similarly,
      miR-155 deficiency abrogated the increased numbers of interferon-gamma expressing
      CD4+ T cells typically observed in wild-type mice in this model. The frequency of
      systemic and mucosal T helper type 17-, CCR9-expressing CD4+ T cells was also
      reduced in miR-155(-/-) mice compared with control mice. These findings strongly
      support a role for miR-155 in facilitating pro-inflammatory cellular responses in
      this model of IBD. Loss of miR-155 also results in decreases in T helper type
      1/type 17, CD11b+) and CD11c+ cells, which correlated with reduced clinical
      scores and severity of disease. miR-155 may serve as a potential therapeutic
      target for the treatment of IBD.

PMID- 24891209
TI  - Preventable readmissions to surgical services: lessons learned and targets for
      improvement.
AB  - BACKGROUND: Hospital readmissions are under intense scrutiny as a measure of
      health care quality. The Center for Medicare and Medicaid Services (CMS) has
      proposed using readmission rates as a benchmark for improving care, including
      targeting them as nonreimbursable events. Our study aim was to describe
      potentially preventable readmissions after surgery and to identify targets for
      improvement. STUDY DESIGN: Patients discharged from a general surgery service
      over 8 consecutive quarters (Q4 2009 to Q3 2011) were selected. A working group
      of attending surgeons defined terms and created classification schemes. Thirty
      day readmissions were identified and reviewed by a 2-physician team. Readmissions
      were categorized as preventable or unpreventable, and by target for future
      quality improvement intervention. RESULTS: Overall readmission rate was 8.3% (315
      of 3,789). The most common indication for initial admission was elective general
      surgery. Among readmitted patients in our sample, 28% did not undergo an
      operation during their index admission. Only 21% (55 of 258) of readmissions were
      likely preventable based on medical record review. Of the preventable
      readmissions, 38% of patients were discharged within 24 hours and 60% within 48
      hours. Dehydration occurred more frequently among preventable readmissions (p <
      0.001). Infection accounted for more than one-third of all readmissions. Among
      preventable readmissions, targets for improvement included closer follow-up after
      discharge (49%), management in the outpatient setting (42%), and avoidance of
      premature discharge (9%). CONCLUSIONS: A minority of readmissions may potentially
      be preventable. Targets for reducing readmissions include addressing the clinical
      issues of infection and dehydration as well as improving discharge planning to
      limit both early and short readmissions. Policies aimed at penalizing
      reimbursements based on readmission rates should use clinical data to focus on
      inappropriate hospitalization in order to promote high quality patient care.

PMID- 24891210
TI  - Are procedures codes in claims data a reliable indicator of intraoperative
      splenic injury compared with clinical registry data?
AB  - BACKGROUND: Identifying iatrogenic injuries using existing data sources is
      important for improved transparency in the occurrence of intraoperative events.
      There is evidence that procedure codes are reliably recorded in claims data. The
      objective of this study was to assess whether concurrent splenic procedure codes
      in patients undergoing colectomy procedures are reliably coded in claims data as
      compared with clinical registry data. STUDY DESIGN: Patients who underwent
      colectomy procedures in the absence of neoplastic diagnosis codes were identified
      from American College of Surgeons (ACS) NSQIP data linked with Medicare inpatient
      claims data file (2005 to 2008). A kappa statistic was used to assess coding
      concordance between ACS NSQIP and Medicare inpatient claims, with ACS NSQIP
      serving as the reference standard. RESULTS: A total of 11,367 colectomy patients
      were identified from 212 hospitals. There were 114 patients (1%) who had a
      concurrent splenic procedure code recorded in either ACS NSQIP or Medicare
      inpatient claims. There were 7 patients who had a splenic injury diagnosis code
      recorded in either data source. Agreement of splenic procedure codes between the
      data sources was substantial (kappa statistic 0.72; 95% CI, 0.64-0.79). Medicare
      inpatient claims identified 81% of the splenic procedure codes recorded in ACS
      NSQIP, and 99% of the patients without a splenic procedure code. CONCLUSIONS: It
      is feasible to use Medicare claims data to identify splenic injuries occurring
      during colectomy procedures, as claims data have moderate sensitivity and
      excellent specificity for capturing concurrent splenic procedure codes compared
      with ACS NSQIP.

PMID- 24891211
TI  - Thirty-day outcomes of paraesophageal hernia repair using the NSQIP database:
      should laparoscopy be the standard of care?
AB  - BACKGROUND: Although surgical repair is universally recognized as the gold
      standard for treatment of paraesophageal hernia (PEH), the optimal surgical
      approach is still the subject of debate. To determine which surgical technique is
      safest, we compared the outcomes of laparoscopic (lap), open transabdominal (TA),
      and open transthoracic (TT) PEH repair using the NSQIP database. STUDY DESIGN:
      From 2005 to 2011, we identified 8,186 patients who underwent a PEH repair (78.4%
      lap, 19.2% TA, 2.4% TT). Primary outcome measured was 30-day mortality. Secondary
      outcomes included hospital length of stay, and NSQIP-measured postoperative
      complications. Multivariable analyses were performed to compare the odds of each
      outcome across procedure type (lap, TA, and TT) while adjusting for other
      factors. RESULTS: Transabdominal patients had the highest 30-day mortality rate
      (2.6%), compared with 0.5% in the lap patients (p < 0.001) and 1.5% in TT
      patients. Mean length of stay was statistically significantly longer for TA and
      TT patients (7.8 days and 6.5 days, respectively) compared with lap patients (3.3
      days). After adjusting for age, American Society of Anesthesiologists score,
      emergency cases, functional status, and steroid use, TA patients were nearly 3
      times as likely as lap patients to experience 30-day mortality (odds ratio [OR],
      2.97; 95% CI, 1.69 to 5.20; p < 0.001). Moreover, TA and TT patients had
      significantly increased odds of overall (OR 2.12; 95% CI 1.79 to 2.51; p < 0.001;
      OR 2.73; 95% CI 1.88 to 3.96; p < 0.001; respectively) and serious morbidity (OR
      1.90; 95% CI 1.53 to 2.37, p < 0.001; OR 2.49; 95% CI 1.54 to 4.00; p < 0.001;
      respectively). CONCLUSIONS: In the absence of published data indicating improved
      long-term outcomes after open TA or TT approach, our findings support the use of
      laparoscopy, whenever technically feasible, because it yields improved short-term
      outcomes.

PMID- 24891212
TI  - Accuracy of surgical wound drainage measurements: an analysis and comparison.
AB  - BACKGROUND: Surgical drain tube readings can influence the clinical management of
      the post-operative patient. The accuracy of these readings has not been
      documented in the current literature and this experimental study aims to address
      this paucity. METHODS: Aliquots (10, 25, 40 and 90 mL) of black tea solution
      prepared to mimic haemoserous fluid were injected into UnoVac, RedoVac and
      Jackson-Pratt drain tubes. Nursing and medical staff from a tertiary hospital
      were asked to estimate drain volumes by direct observation; analysis of variance
      was performed on the results and significance level was set at 0.05. RESULTS:
      Doctors and nurses are equally accurate in estimating drain tube volumes. Jackson
      Pratt systems were found to be the most accurate for intermediate volumes of 25
      and 40 mL. For extreme of volumes (both high and low), all drainage systems were
      inaccurate. CONCLUSION: This study suggests that for intermediate volumes (25 and
      40 mL), Jackson-Pratt is the drainage system of choice. The accuracy of volume
      measurement is diminished at the extremes of drain volumes; emptying of drainage
      systems is recommended to avoid overfilling of drainage systems.

PMID- 24891214
TI  - The chlamydial anomaly clarified?
AB  - Getting visible: A new method to label bacterial cell walls shows the presence of
      functional peptidoglycan in the important pathogen Chlamydia trachomatis. This
      might clarify the long-standing paradox of the "chlamydial anomaly". 

PMID- 24891215
TI  - Comparison of Von Willebrand factor (VWF) activity VWF:Ac with VWF ristocetin
      cofactor activity VWF:RCo.
AB  - INTRODUCTION: Ristocetin cofactor activity of Von Willebrand factor (VWF:RCo) and
      the ratio VWF:RCo to its antigen VWF:Ag are used as routine screening to estimate
      VWF function and to detect types of Von Willebrand disease (VWD) caused by loss
      of high molecular weight multimers. However, the VWF:RCo test is prone to
      analytic imprecisions due to various reasons. We compared an assay for VWF
      activity (VWF:Ac) with VWF:RCo putting emphasis on the ratios to VWF:Ag.
      MATERIALS AND METHODS: We evaluated 942 samples from 432 patients and evaluated
      three groups in detail: normal patients (normal multimers, VWF:Ag and VWF:RCo
      >0.5 U/ml, VWD type 1 excluded; n=258), VWD type 1 (n=76) and acquired Von
      Willebrand syndrome (AVWS, n=326). In addition, 30 healthy subjects were
      analysed. RESULTS: VWF:Ac and VWF:RCo correlated well (Pearson's r=0.96, p<0.01),
      so did their ratios to VWF:Ag (Pearson's r=0.82, p<0.01). We calculated the
      normal range of VWF:Ac/VWF:Ag for healthy subjects as 0.8-1.16. In comparison,
      the reference range (mean+/-2std) derived from normal patient samples was 0.73
      1.14. The corresponding ranges for VWF:RCo/VWF:Ag came to 0.74-1.23 (healthy) and
      0.62-1.25 (normal patients). The ratios showed similar results regarding VWD type
      1. The sensitivity for AVWS was higher with VWF:Ac/VWF:Ag than with
      VWF:RCo/VWF:Ag (97.5% versus 84.7%). CONCLUSIONS: The data suggest that the
      results obtained with the VWF:Ac assay are comparable to that of the VWF:RCo
      assay. An AVWS was more reliably detected by VWF:Ac/VWF:Ag. We assume that the
      VWF:Ac assay could replace VWF:RCo for routine screening for AVWS, especially
      when prompt evaluation is required.

PMID- 24891216
TI  - The development of diabetes among Danish cystic fibrosis patients over the last
      two decades.
AB  - OBJECTIVE: Cystic fibrosis (CF)-related diabetes (CFRD) is correlated with age
      and has been associated with a decline in body mass index (BMI), pulmonary
      function, and survival. Over the last two decades, the focus has been on the
      early diagnosis and treatment of diabetes; therefore, in this study, we evaluated
      the status of the current clinical condition and survival in our CF population.
      In addition, we also aimed to investigate the incidence of diabetes among
      adolescence over time and to identify characteristics associated with early
      diabetes onset. METHODS: A retrospective chart review of a birth cohort
      consisting of 161 CF patients born between 1975 and 1994 and followed until 2011.
      RESULTS: Over two decades, the incidence of CFRD among 11- to 16-year-old
      children remained unchanged at 12-14%, while the proportion of children with
      chronic pulmonary infection at age 10 declined from 31 to 8% (p < 0.001). Severe
      CF-mutation, i.e., group I and II mutations, were associated with diabetes (p =
      0.003). Female gender was borderline associated with diabetes among adolescents
      (p = 0.06). No significant worsening in pulmonary function, BMI or survival was
      identified when comparing CFRD patients to CF patients without CFRD. CONCLUSIONS:
      The incidence of diabetes among adolescence with CF has not changed over the last
      two decades. Severe CF mutations are a risk factor for CFRD, and female gender is
      borderline associated with CFRD among adolescents. Pulmonary function, BMI and
      survival were comparable regardless of the onset of CFRD.

PMID- 24891213
TI  - Continuing challenges in influenza.
AB  - Influenza is an acute respiratory disease in mammals and domestic poultry that
      emerges from zoonotic reservoirs in aquatic birds and bats. Although influenza
      viruses are among the most intensively studied pathogens, existing control
      options require further improvement. Influenza vaccines must be regularly updated
      because of continuous antigenic drift and sporadic antigenic shifts in the viral
      surface glycoproteins. Currently, influenza therapeutics are limited to
      neuraminidase inhibitors; novel drugs and vaccine approaches are therefore
      urgently needed. Advances in vaccinology and structural analysis have revealed
      common antigenic epitopes on hemagglutinins across all influenza viruses and
      suggest that a universal influenza vaccine is possible. In addition, various
      immunomodulatory agents and signaling pathway inhibitors are undergoing
      preclinical development. Continuing challenges in influenza include the emergence
      of pandemic H1N1 influenza in 2009, human infections with avian H7N9 influenza in
      2013, and sporadic human cases of highly pathogenic avian H5N1 influenza. Here,
      we review the challenges facing influenza scientists and veterinary and human
      public health officials; we also discuss the exciting possibility of achieving
      the ultimate goal of controlling influenza's ability to change its antigenicity. 

PMID- 24891217
TI  - Sun exposure: perceptions and behaviours in outdoor workers.

PMID- 24891218
TI  - STAT3 signaling is activated preferentially in tumor-initiating cells in claudin
      low models of human breast cancer.
AB  - In breast cancer, a subset of tumor-initiating cells (TIC) or "cancer stem cells"
      are thought to be responsible for tumor maintenance, treatment resistance, and
      disease recurrence. While current breast cancer stem cell markers (e.g.,
      CD44(high) /CD24(low/neg) , ALDH positive) have allowed enrichment for such
      cells, they are not universally expressed and may actually identify distinct TIC
      subpopulations in the same tumor. Thus, additional markers of functional stem
      cells are needed. The STAT3 pathway is a critical regulator of the function of
      normal stem cells, and evidence is accumulating for its important role in breast
      cancer stem cells. However, due to the lack of a method for separating live cells
      based on their level of STAT3 activity, it remains unknown whether STAT3
      functions in the cancer stem cells themselves, or in surrounding niche cells, or
      in both. To approach this question, we constructed a series of lentiviral
      fluorescent (enhanced green fluorescent protein, EGFP) reporters that enabled
      flow cytometric enrichment of cells differing in STAT3-mediated transcriptional
      activity, as well as in vivo/in situ localization of STAT3 responsive cells.
      Using in vivo claudin-low cell line xenograft models of human breast cancer, we
      found that STAT3 signaling reporter activity (EGFP(+) ) is associated with a
      subpopulation of cancer cells enriched for mammosphere-forming efficiency, as
      well as TIC function in limiting dilution transplantation assays compared to
      negative or unsorted populations. Our results support STAT3 signaling activity as
      another functional marker for human breast cancer stem cells thus making it an
      attractive therapeutic target for stem-cell-directed therapy in some breast
      cancer subtypes.

PMID- 24891219
TI  - Pin1 regulates osteoclast fusion through suppression of the master regulator of
      cell fusion DC-STAMP.
AB  - Cell fusion is a fundamental biological event that is essential for the
      development of multinucleated cells such as osteoclasts. Fusion failure leads to
      the accumulation of dense bone such as in osteopetrosis, demonstrating the
      importance of fusion in osteoclast maturity and bone remodeling. In a recent
      study, we reported that Pin1 plays a role in the regulation of bone formation and
      Runx2 regulation. In this study, we explored the role of Pin1 in osteoclast
      formation and bone resorption. Pin1 null mice have low bone mass and increased
      TRAP staining in histological sections of long bones, compared to Pin1 wild-type
      mice. In vitro osteoclast forming assays with bone marrow-derived
      monocyte/macrophage revealed that Pin1-deficient osteoclasts are larger than wild
      type osteoclasts and have higher nuclei numbers, indicating greater extent of
      fusion. Pin1 deficiency also highly enhanced foreign body giant cell formation
      both in vitro and in vivo. Among the known fusion proteins, only DC-STAMP was
      significantly increased in Pin1(-/-) osteoclasts. Immunohistochemistry showed
      that DC-STAMP expression was also significantly increased in tibial metaphysis of
      Pin1 KO mice. We found that Pin1 binds and isomerizes DC-STAMP and affects its
      expression levels and localization at the plasma membrane. Taken together, our
      data indicate that Pin1 is a determinant of bone mass through the regulation of
      the osteoclast fusion protein DC-STAMP. The identification of Pin1 as a factor
      involved in cell fusion contributes to the understanding of osteoclast-associated
      diseases, including osteoporosis, and opens new avenues for therapeutic targets.

PMID- 24891220
TI  - Combining the alpha1 -adrenergic receptor antagonist, prazosin, with the beta
      adrenergic receptor antagonist, propranolol, reduces alcohol drinking more
      effectively than either drug alone.
AB  - BACKGROUND: Evidence suggests that activation of the noradrenergic system may
      contribute to alcohol drinking in animals and humans. Our previous studies
      demonstrated that blocking alpha1 -adrenergic receptors with the antagonist,
      prazosin, decreased alcohol drinking in rats under various conditions. As
      noradrenergic activation is also regulated by beta-adrenergic receptors, we now
      examine the effects of the beta-adrenergic receptor antagonist, propranolol,
      alone or in combination with prazosin, on alcohol drinking in rats selectively
      bred for high voluntary alcohol intake and alcohol preference (P line). METHODS:
      Two studies were conducted with male P rats. In study 1, rats were allowed to
      become alcohol-dependent during 14 weeks of ad libitum access to food, water, and
      20% alcohol, and the effect of propranolol (5 to 15 mg/kg, intraperitoneally
      [IP]) and prazosin (1 to 2 mg/kg, IP) on alcohol intake during withdrawal was
      assessed. In study 2, the effect of propranolol (5 mg/kg, IP) and prazosin (2
      mg/kg, IP) on alcohol intake following prolonged imposed abstinence was assessed.
      RESULTS: Alcohol drinking following propranolol treatment was variable, but the
      combination of propranolol + prazosin consistently suppressed alcohol drinking
      during both alcohol withdrawal and following prolonged imposed abstinence, and
      the combination of these 2 drugs was more effective than was treatment with
      either drug alone. CONCLUSIONS: Treatment with prazosin + propranolol, or a
      combination of other centrally active alpha1 - and beta-adrenergic receptor
      antagonists, may assist in preventing alcohol relapse in some individuals.

PMID- 24891221
TI  - T3-T4 laryngeal cancer in The Netherlands Cancer Institute; 10-year results of
      the consistent application of an organ-preserving/-sacrificing protocol.
AB  - BACKGROUND: Both organ-preserving concurrent (chemo)radiotherapy ((C)RT) and
      organ-sacrificing surgery (total laryngectomy) are used for treatment of advanced
      laryngeal cancer. The purpose of this study was to present the assessment of our
      treatment protocol for T3 (C)RT and T4 disease (total laryngectomy +
      postoperative RT). METHODS: We conducted a retrospective cohort study in 182
      consecutive patients (1999-2008). The primary outcome was overall survival (OS)
      in relation to stage and treatment. RESULTS: One hundred two patients received RT
      (82.4% T3), 20 patients CRT (60.0% T3), and 60 patients total laryngectomy + RT
      (91.7% T4). Five-year OS: T3 52%, T4 48%, for RT 50%, for CRT 43%, and for total
      laryngectomy + RT 52%. Five-year laryngectomy-free interval was 72% after RT, and
      83% after CRT. CONCLUSION: There were no differences in survival according to T
      classification or treatment modality. Because the majority of T3 laryngeal
      cancers were treated with (C)RT and the majority of T4 with total laryngectomy +
      RT, this gives food for thought on whether the present protocol for T3 laryngeal
      cancer is optimal.

PMID- 24891222
TI  - Acetylated 1,3-diaminopropane antagonizes abscisic acid-mediated stomatal closing
      in Arabidopsis.
AB  - Faced with declining soil-water potential, plants synthesize abscisic acid (ABA),
      which then triggers stomatal closure to conserve tissue moisture. Closed
      stomates, however, also create several physiological dilemmas. Among these, the
      large CO2 influx required for net photosynthesis will be disrupted. Depleting CO2
      in the plant will in turn bias stomatal opening by suppressing ABA sensitivity,
      which then aggravates transpiration further. We have investigated the molecular
      basis of how C3 plants resolve this H2 O-CO2 conflicting priority created by
      stomatal closure. Here, we have identified in Arabidopsis thaliana an early
      drought-induced spermidine spermine-N(1) -acetyltransferase homolog, which can
      slow ABA-mediated stomatal closure. Evidence from genetic, biochemical and
      physiological analyses has revealed that this protein does so by acetylating the
      metabolite 1,3-diaminopropane (DAP), thereby turning on the latter's intrinsic
      activity. Acetylated DAP triggers plasma membrane electrical and ion transport
      properties in an opposite way to those by ABA. Thus in adapting to low soil-water
      availability, acetyl-DAP could refrain stomates from complete closure to sustain
      CO2 diffusion to photosynthetic tissues.

PMID- 24891224
TI  - Study of selenium intake and disposition in various matrices based on
      mathematical algorithms derived from pooled biomonitoring data.
AB  - Biomonitoring is increasingly used to assess exposure to selenium (Se) in the
      population. However, there is little harmonization among protocols used in the
      different studies (varying biological matrices, differences in expression of
      results (concentrations versus amounts, units)). This makes inter-comparison of
      biomonitoring results across studies difficult. From a public health risk
      perspective, it also becomes challenging to estimate baseline levels in
      biological matrices for populations exposed by various sources. The aim of this
      study was thus to perform a systematic analysis of the relationship between Se
      intakes and biological concentrations based on published data. Inclusion and
      exclusion criteria were used and led to select 75 published biomonitoring data in
      humans from an extended review of Se biomonitoring studies. This represents 8 628
      individuals who provided biological samples aiming at documenting Se exposure
      and/or Se concentrations in two or more biological matrices. Mathematical
      algorithms that relate Se intakes to biological concentrations and establish
      matrix-to-matrix associations were derived from these pooled biomonitoring data.
      Logarithmic regressions showed good correlations between Se intakes and whole
      blood concentrations (R(2)=0.884), plasma concentrations (R(2)=0.863) and urinary
      excretion rates (R(2)=0.958). Blood and plasma concentrations were also strongly
      related (R(2)=0.874), as were whole blood concentrations and urinary excretion
      rates (R(2)=0.953). The interpretation of the log-regression coefficients allowed
      illustrating Se physiology. Se concentrations in plasma tend to plateau when
      daily intake exceed 150 MUg/d, whereas Se in urine increases rapidly above this
      threshold. The application of the algorithms to other independent data sets in
      order to reconstruct past Se intakes confirmed that interpretation of results on
      the basis of Se in integuments may be misleading if external contamination is not
      avoided. This approach based on pooled data covered a wide range of exposure and
      the large number of data integrated increased the level of confidence of results.

PMID- 24891223
TI  - Kidney transplant access in the Southeast: view from the bottom.
AB  - The Southeastern region of the United States has the highest burden of end-stage
      renal disease (ESRD) but the lowest rates of kidney transplantation in the
      nation. There are many patient-, dialysis facility-, ESRD Network- and health
      system-level barriers that contribute to this regional disparity. Compared to the
      rest of the nation, the Southeast has a larger population of African-Americans
      and higher poverty, as well as more prevalent ESRD risk factors including
      hypertension, obesity and diabetes. Dialysis facilities--where ESRD patients
      receive the majority of their healthcare--play an important role in transplant
      access. Identifying characteristics of individual dialysis units with low rates
      of kidney transplantation, such as understaffing or for-profit status, can help
      identify targets for quality improvement initiatives. Geographic differences
      across the country can identify opportunities to increase funding for healthcare
      resources in proportion to patient and disease burden. Focusing interventions
      among dialysis facilities with the lowest transplant rates within the Southeast,
      such as provider and patient education, has the potential to increase referrals
      for kidney transplantation, leading to higher rates of kidney transplants in this
      region. Referral for transplantation should be measured on a national level to
      monitor disparities in early access to transplantation. Transplant centers have
      an obligation to assist underserved populations in ensuring equity in access to
      services. Policies that improve access to care for patients, such as the
      Affordable Care Act and Medicaid expansion, are particularly important for
      Southern states and may alleviate geographic disparities.

PMID- 24891225
TI  - Highly efficient enzymatic synthesis of an ascorbyl unstaturated fatty acid ester
      with ecofriendly biomass-derived 2-methyltetrahydrofuran as cosolvent.
AB  - Enzymatic synthesis of ascorbyl undecylenate, an unsaturated fatty acid ester of
      ascorbic acid, was reported with biomass-derived 2-methyltetrahydrofuran (MeTHF)
      as the cosolvent. Of the immobilized lipases tested, Candida antarctica lipase B
      (CAL-B) showed the highest activity for enzymatic synthesis of ascorbyl
      undecylenate. Effect of reaction media on the enzymatic reaction was studied. The
      cosolvent mixture, t-butanol-MeTHF (1:4, v/v) proved to be the optimal medium, in
      which not only ascorbic acid had moderate solubility, but also CAL-B showed a
      high activity, thus addressing the major problem of the solvent conflict for
      dissolving substrate and keeping satisfactory enzyme activity. In addition, the
      enzyme was much more stable in MeTHF and t-butanol-MeTHF (1:4) than in previously
      widely used organic solvents, t-butanol, 2-methyl-2-butanol, and acetone. The
      much higher initial reaction rate in this cosolvent mixture may be rationalized
      by the much lower apparent activation energy of this enzymatic reaction (26.6 vs.
      38.1-39.1 kJ/mol) and higher enzyme catalytic efficiency (Vmax /Km , 8.4 vs. 1.3
      1.4 h(-1) ). Ascorbyl undecylenate was obtained with the yields of 84-89% and 6
      regioselectivity of >99% in t-butanol-MeTHF (1:4) at supersaturated substrate
      concentrations (60 and 100 mM) after 5-8 h.

PMID- 24891226
TI  - Combined multispectroscopic and molecular docking investigation on the
      interaction between delphinidin-3-O-glucoside and bovine serum albumin.
AB  - Anthocyanin is one of the flavonoid phytopigments with specific health benefits.
      The interaction between delphinidin-3-O-glucoside (D3G) and bovine serum albumin
      (BSA) was investigated by fluorescence spectroscopy, synchronous fluorescence
      spectroscopy, three-dimensional fluorescence spectroscopy, ultraviolet-visible
      absorption spectroscopy, circular dichroism spectroscopy and molecular modeling.
      D3G effectively quenched the intrinsic fluorescence of BSA via static quenching.
      The number of binding sites and binding constant Ka were determined, and the
      hydrogen bonds and van der Waals forces played major roles in stabilizing the D3G
      BSA complex. The distance r between donor and acceptor was obtained as 2.81 nm
      according to Forster's theory. In addition, the effects of pH and metal ions on
      the binding constants were discussed. The results studied by synchronous
      fluorescence, three-dimensional fluorescence and circular dichroism experiments
      indicated that the secondary structures of the protein has been changed by the
      addition of D3G and the alpha-helix content of BSA decreased (from 56.1% to
      52.4%). Furthermore, the study of site marker competitive experiments and
      molecular modeling indicated that D3G could bind to site I of BSA, which was in
      the large hydrophobic cavity of subdomain IIA.

PMID- 24891227
TI  - Impact of pocket ultrasound use by internal medicine housestaff in the diagnosis
      of dyspnea.
AB  - BACKGROUND: Recent reports demonstrate high diagnostic accuracy of lung
      ultrasound for evaluation of dyspnea. We assessed the feasibility of training
      internal medicine residents in lung ultrasound with a pocket ultrasound device.
      METHODS: We performed a prospective, observational trial of residents performing
      lung ultrasound with a pocket ultrasound. Training consisted of two 90-minute
      sessions of didactics and supervised bedside performance. Two residents received
      an additional 2 weeks of training. Residents recorded a clinical diagnosis based
      on admission data. Following lung ultrasound performance, an ultrasound diagnosis
      was recorded integrating clinical and sonographic findings. Using receiver
      operating curve analysis, the area under the curve was calculated for both
      clinical diagnosis and ultrasound diagnosis using attending physician's final
      discharge diagnosis as the gold standard. RESULTS: Five residents performed 69
      exams. The AUC for ultrasound diagnosis was significantly higher than that for
      clinical diagnosis (0.87 vs 0.81, P < 0.01). AUCs increased using lung ultrasound
      for diagnoses as follows: chronic obstructive pulmonary disease (0.73-0.85, P =
      0.06), acute pulmonary edema (0.85-0.89, P = 0.49), pneumonia (0.77-0.88, P =
      0.01), and pleural effusions (0.76-0.96, P < 0.002). CONCLUSIONS: Lung ultrasound
      performed by residents with a pocket ultrasound improved the diagnostic accuracy
      of dyspnea. Two residents undergoing extended training showed a total increase in
      diagnostic accuracy.

PMID- 24891228
TI  - How the modified Clinical Pulmonary Infection Score can identify treatment
      failure and avoid overusing antibiotics in ventilator-associated pneumonia.
AB  - AIM: Although the modified Clinical Pulmonary Infection Score (CPIS) has been
      used to guide treatment decisions in adults with ventilator-associated pneumonia
      (VAP), paediatric studies are lacking. We assessed a modified CPIS tool to define
      VAP resolution and identify treatment failure at an early stage. METHODS: We
      identified 70 mechanically ventilated children with VAP according to the Center
      for Disease Control criteria. Modified CPIS was initially measured at VAP onset
      and then three and five days afterwards. Children were defined as low risk or
      high risk based on a cut-off score of six. RESULTS: There were 50 high-risk and
      20 low-risk patients. Culture results were positive in 64% of the high-risk
      patients and just 10% of the low-risk patients. Patients on adequate therapy
      significantly improved their CPIS scores by day three, regardless of the
      likelihood of VAP. A lack of score improvement demonstrated sensitivity of 100%
      and specificity of 83% when it came to detecting treatment failure. The area
      under the receiver operating curve was 0.92. CONCLUSION: Serial modified CPIS
      measurements showed that low-risk patients with negative cultures at day three
      should be considered for a short course of antibiotics. In contrast, high-risk
      patients with no score improvement were potentially failing their treatment.

PMID- 24891229
TI  - Genetic parameters and breeding values for semen characteristics in Hanoverian
      stallions.
AB  - The objectives of this study were to show whether semen traits of 30 Hanoverian
      stallions regularly used in AI may be useful for breeding purposes. Semen
      characteristics were studied using 15 149 ejaculates from 30 Hanoverian stallions
      of the State Stud Celle of Lower Saxony. Semen samples were collected between
      2005 and 2009. Traits analysed were gel-free volume, sperm concentration, total
      and motile sperm number and progressive motility. A linear multivariate animal
      model was employed to estimate heritabilities and permanent environmental
      variances for stallions. The same model was used to predict breeding values for
      all traits simultaneously. Heritabilities were high for gel-free volume (h(2) =
      0.43) and moderate for total number of sperm (h(2) = 0.29) and progressive
      motility (h(2) = 0.20). Gel-free volume, sperm concentration and total number of
      sperm were genetically negatively correlated with progressive motility. The
      effect of the permanent environment for stallions accounted for 9-55% of the
      trait variance. The total variance among stallions explained 37-69% of the trait
      variance. The average reliabilities of the breeding values were 0.43-0.76 for the
      30 Hanoverian stallions. In conclusion, the study could demonstrate large effects
      of stallions, routinely employed in a breeding programme, on semen
      characteristics analysed here. We could demonstrate that estimated breeding
      values (EBV) with sufficient high reliabilities can be predicted using data from
      these stallions and these EBV are useful in horse breeding programmes to achieve
      genetic improvement in semen quality.

PMID- 24891230
TI  - Did compulsory wear regulations increase personal flotation device (PFD) use by
      boaters in small power recreational vessels? A before-after observational study
      conducted in Victoria, Australia.
AB  - OBJECTIVE: To estimate the effect of the 2005 Victorian mandatory personal
      flotation device (PFD) wearing regulations on PFD use by occupants of small (hull
      length <=4.8 m) power recreational vessels. DESIGN: Before-after observational
      study investigating the probability of PFD use among occupants of small vessels
      before and after the regulations were introduced compared with the probability of
      use by their counterparts on large power vessels (hull length >4.8-12 m) who were
      not required to wear PFDs before or after the regulations were introduced in the
      low-risk conditions in which observations occurred. METHODS: Statewide
      observation surveys of boaters were conducted in peak boating periods between
      January and March 2005 (prelegislation) and 2007 (postlegislation). Data
      collection included size of vessel, age and sex of boaters, life jacket use, boat
      type, activity of boaters, type of waterway and weather and water conditions.
      Logistic regression modelling tested whether there were statistically significant
      differences in the change in the relative odds of occupants wearing PFDs from the
      preintervention to the postintervention period in small compared with large power
      recreational vessels. RESULTS: The probability of PFD use increased from 22% to
      63% on small power vessels compared with 12% to 13% on large vessels. Regression
      analysis showed a high statistically significant increase in the odds of PFD use
      on small vessels relative to large vessels (OR 6.2, 95% CI 4.2 to 9.3, p<0.001).
      No statistically significant effect on use on large vessels was associated with
      the regulation (OR 1.27, 95% CI 0.94 to 1.70, p=0.15). Relative to large vessels,
      on small vessels the odds of PFD use increased significantly in both sexes, all
      age groups, all vessel types and activity groupings except for towed water sports
      where the increase was only marginally statistically significant. CONCLUSIONS:
      The legislative intervention was successful in increasing PFD wearing in small
      vessels. However, visible enforcement and tougher penalties are needed to
      optimise compliance.

PMID- 24891232
TI  - Bactericidal thurincin H causes unique morphological changes in Bacillus cereus
      F4552 without affecting membrane permeability.
AB  - Thurincin H is an antilisterial bacteriocin produced by Bacillus thuringiensis
      SF361. It exhibits inhibitory activity against a wide range of Gram-positive
      foodborne pathogens and spoilage bacteria including Listeria monocytogenes, B.
      cereus, and B. subtilis. This hydrophobic, anionic bacteriocin folds into a
      hairpin structure maintained by four pairs of unique sulfur to alpha-carbon
      thioether bonds. As its hydrophobicity and structure are quite different from
      most archived bacteriocins, this study aimed to elucidate its mode of action and
      compare it with the mechanisms of other well-characterized bacteriocins. The
      results indicated that, although bactericidal to B. cereus F4552, thurincin H did
      not lead to optical density reduction or detectable changes in cell membrane
      permeability. B. cereus F4552 imaged by scanning electron microscopy after
      treatment with thurincin H at 32 * MIC showed regular rod-shaped cells, while
      only cells treated with thurincin H at the elevated levels of 256 * MIC showed
      loss of cell integrity and rigidity. Both concentrations caused greater than 99%
      of cell viability reduction. In contrast, nisin caused significant cell membrane
      permeability at concentration as low as 2 * MIC. These results indicated a
      difference in the mode of action for thurincin H compared with the generalized
      pore-forming mechanism of many lantibiotics, such as nisin.

PMID- 24891231
TI  - Trends in the use of evidence-based therapy for resectable gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Two pivotal randomized controlled trials (RCTs), the
      Intergroup (INT-0116) and Medical Research Council Adjuvant Gastric Infusional
      Chemotherapy (MAGIC) trials, demonstrated a survival benefit of multimodality
      therapy in patients with resectable gastric cancer. The purpose of this study was
      to determine utilization rates of these treatment regimens in the United States
      and to identify factors associated with receipt of evidence-based care. METHODS:
      We performed a retrospective cohort study of patients with Stage IB-IV (M0)
      gastric adenocarcinoma who underwent resection from 1991 to 2009 using the linked
      SEER-Medicare database. RESULTS: Only 19.1% of patients received post-operative
      chemoradiation therapy (CRT), and 1.9% received peri-operative chemotherapy; most
      patients underwent surgery alone (60.9%). Patients with more advanced stage,
      younger age, and fewer comorbidities were more likely to receive evidence-based
      care. We found no association between National Cancer Institute (NCI) designation
      and delivery of multimodality therapy. However, patients who underwent medical
      oncology consultation were much more likely to receive evidence-based treatment
      (OR 3.10, 95% CI 2.35-4.09). CONCLUSIONS: Rates of peri-operative chemotherapy
      and post-operative CRT in patients with resected gastric cancer remain remarkably
      low, despite high-quality RCT evidence demonstrating their benefit. Furthermore,
      NCI designation does not appear to be associated with administration of evidence
      based treatment.

PMID- 24891233
TI  - Cholangiocarcinoma cell line TK may be useful for the pharmacokinetic study of
      the chemotherapeutic agent gemcitabine.
AB  - Cholangiocarcinoma is a disease with a poor prognosis. A human cholangiocarcinoma
      cell line, TK, was previously established to enable further understanding of the
      disease. We conducted this investigation to determine whether or not the TK line
      is useful for pharmacokinetic study of the chemotherapeutic agent gemcitabine
      (GEM). Along with the BXPC3 human pancreatic adenocarcinoma cell line, the
      sensitivity to and effects on the TK cell line of GEM were compared. The
      influence of deoxycytidine kinase (dCK) transduction was also comparatively
      investigated. The effects of GEM in terms of drug sensitivity of the TK cell
      line, cell cycle and levels of transcripts of key enzymes were comparable to the
      BXPC3 cell line. Responses to the drug were similar in both cell lines. In
      contrast to pancreatic carcinoma, cell lines for research on cholangiocarcinoma
      have been limited. This study suggests the application of the TK cell line to the
      pharmacokinetic study of the chemosensitization of therapeutic drugs, such as
      GEM.

PMID- 24891234
TI  - Palladium-catalyzed insertion of an allene into an aminal: aminomethylamination
      of allenes by C-N bond activation.
AB  - A new and atom-economic palladium-catalyzed aminomethylamination of allenes with
      aminals by C?N bond activation is described. This direct and operationally simple
      method provides a fundamentally novel approach for the synthesis of 1,3-diamines.
      Mechanistic studies suggest that a unique cationic pi-allylpalladium complex
      containing an aminomethyl moiety is generated as a key intermediate through the
      carbopalladation of the allene with a cyclometalated palladium-alkyl species. 

PMID- 24891235
TI  - Maternal 25-hydroxyvitamin D level and fetal bone growth assessed by ultrasound:
      a systematic review.
AB  - OBJECTIVES: To assess systematically the role of maternal vitamin D levels in
      fetal bone growth. METHODS: PubMed, EMBASE and Cochrane databases were searched
      using the search words [Vitamin D] in combination with [fetal, fetus,
      intrauterine, or prenatal AND growth, development, bone, femur, or humerus];
      [crown-rump length]; or [ultrasonography, prenatal]. Criteria for inclusion in
      this systematic review were data on maternal serum 25-hydroxyvitamin D (25(OH)D)
      during pregnancy and measurement of fetal growth by ultrasound. RESULTS: We
      identified 750 publications initially, from which five observational studies were
      selected for inclusion in the final review. The parameters studied were humerus
      length (HL) and femur length (FL) and their Z-scores, femoral volume, femoral
      distal metaphyseal cross-sectional area (CSA), femoral proximal metaphyseal
      diameter (PMD), femoral mid-shaft diameter and crown-rump length. In one study,
      25(OH)D was associated directly with FL; in another study 25(OH)D only correlated
      with FL and HL Z-scores when calcium intake was insufficient. Two studies found
      no association between 25(OH)D and FL, but detected a direct association with
      femoral PMD, and an inverse relation with femoral distal metaphyseal CSA,
      respectively. CONCLUSIONS: Observational studies investigating the role of
      maternal vitamin D levels in fetal bone growth are sparse. Their evidence
      suggests that low maternal 25(OH)D levels may affect fetal bone growth under
      certain circumstances, especially in cases of simultaneous low calcium intake.
      Further studies are necessary.

PMID- 24891236
TI  - Treatment-related amenorrhea and sexual functioning in young breast cancer
      survivors.
AB  - BACKGROUND: Sexual dysfunction is a known complication of adjuvant therapy for
      breast cancer and an important determinant of quality of life. However, few
      studies have explored how treatment and other factors affect sexual functioning
      in young breast cancer survivors. METHODS: Four hundred sixty-one premenopausal
      women with stage 0 through III breast cancer were surveyed an average of 1 year
      after diagnosis as part of a prospective cohort study of women who were aged <=40
      years at diagnosis. Sexual interest and dysfunction were assessed using the
      Cancer Rehabilitation Evaluation System (CARES). Mean CARES scores were compared
      and multiple regression models were fit to assess treatment and a range of
      menopausal and somatic symptoms in relation to sexual functioning. RESULTS: Mean
      CARES sexual interest and dysfunction scores were both highest (indicating poorer
      functioning) among women who received chemotherapy and were amenorrheic from
      treatment. After accounting for menopausal and somatic symptoms, treatment
      associated amenorrhea remained associated with decreased interest but was no
      longer an independent predictor of dysfunction. In the multivariable analysis,
      independent predictors of dysfunction included vaginal pain symptoms, poorer body
      image, and fatigue. Sexual interest was associated with vaginal pain symptoms,
      body image, and weight problems. CONCLUSIONS: Factors associated with decreased
      sexual functioning in young breast cancer survivors can often be ameliorated. The
      current findings have implications for premenopausal women with other types of
      cancer who might be experiencing amenorrhea because of chemotherapy or surgery.
      Increased awareness and early intervention is essential to help improve sexual
      functioning and associated quality of life for all young cancer survivors.

PMID- 24891237
TI  - Cell autonomous regulation of hippocampal circuitry via Aph1b-gamma
      secretase/neuregulin 1 signalling.
AB  - Neuregulin 1 (NRG1) and the gamma-secretase subunit APH1B have been previously
      implicated as genetic risk factors for schizophrenia and schizophrenia relevant
      deficits have been observed in rodent models with loss of function mutations in
      either gene. Here we show that the Aph1b-gamma-secretase is selectively involved
      in Nrg1 intracellular signalling. We found that Aph1b-deficient mice display a
      decrease in excitatory synaptic markers. Electrophysiological recordings show
      that Aph1b is required for excitatory synaptic transmission and plasticity.
      Furthermore, gain and loss of function and genetic rescue experiments indicate
      that Nrg1 intracellular signalling promotes dendritic spine formation downstream
      of Aph1b-gamma-secretase in vitro and in vivo. In conclusion, our study sheds
      light on the physiological role of Aph1b-gamma-secretase in brain and provides a
      new mechanistic perspective on the relevance of NRG1 processing in schizophrenia.

PMID- 24891239
TI  - Tocilizumab treatment leads to a rapid and sustained increase in Treg cell levels
      in rheumatoid arthritis patients: comment on the article by Thiolat et al.

PMID- 24891240
TI  - [Specialization in oncosurgery is not against the surgeons best interest].
AB  - An analysis of the current situation in the surgical treatment of solid malignant
      tumors in the Czech Republic demonstrates the need to impose a concept of
      oncosurgical care, which would lead to a steady improvement in the quality of
      care provided by surgeons in oncosurgery. The primary aim is that surgery plays
      an appropriate role in the complex care of oncology patients and that surgeons
      become equal partners to radiation and internal oncologists in the determination
      of diagnostic - therapeutic plans and in other decision-making processes. This
      aim is not possible without increasing the qualification of surgeons in
      oncosurgery. Our more than ten year effort culminated in 2011 with the
      introduction of the specialized field of oncosurgery into the postgradual
      education of surgeons; and as such, similarly to most other developed countries,
      provided the official opportunity to educate surgeons in the field of oncology.
      Other important tasks which would contribute to increasing the quality of
      oncosurgery include rational concentration of oncosurgical operations to a
      smaller number of surgical departments, where it is necessary to ensure both the
      improvement of surgeon qualification by way of oncosurgical specialization, as
      well as adequate material and financial support for complex oncosurgical
      procedures.

PMID- 24891238
TI  - Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the
      genetic code.
AB  - Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the
      genetic code and ultimately select the correct amino acids to be used in protein
      synthesis. The physiological necessity of these quality control mechanisms in
      different environments remains unclear, as the cost vs benefit of accurate
      protein synthesis is difficult to predict. We show that in Escherichia coli, a
      non-coded amino acid produced through oxidative damage is a significant threat to
      the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA
      synthetase in order to prevent cellular toxicity caused by mis-synthesized
      proteins. These findings demonstrate how stress can lead to the accumulation of
      non-canonical amino acids that must be excluded from the proteome in order to
      maintain cellular viability. 

PMID- 24891241
TI  - [Complications after percutaneous transhepatic drainage of the biliary tract].
AB  - INTRODUCTION: The aim of this work is to demonstrate perioperative and
      postoperative complications after percutaneous transhepatic drainage of the
      biliary tract and, on the basis of our own experience, to show the possibilities
      of solving these complications within hospital care as well as the ways of
      preventing such complications in outpatient and home care where the role of home
      care nurses is very important. MATERIAL AND METHODS: At the Department of
      Radiology in F.D. Roosevelt Teaching Hospital Banska Bystrica, more than 100
      percutaenous transhepatic biliary tract drainage procedures are performed every
      year. In 2013, 105 such procedures were performed. Indications included
      nonresectable cholangiocarcinomas of the biliary confluence (Klatskin tumours) or
      common bile duct as well as benign bile obstructions in which endoscopic drainage
      could not be performed (benign stenosis of thecommon bile duct, stenosis of
      biliodigestive anastomosis, intrahepatic biliary stones). Between 2009 and 2013,
      151 patients with percutaneous transhepatic drainage of the biliary tract were
      hospitalised at the Department of Surgery in F.D. Roosevelt Hospital Banska
      Bystrica,of whom 98 had malignant obstruction and 53 benign obstruction. RESULTS:
      In 151 patients hospitalised at the Department of Surgery, the following
      postoperative complications occurred: catheter obliteration in 6.6%, biliary
      peritonitis in 2%, sepsis with cholangitis in 3.3% and haemorrhage in 4.6% of all
      patients. Mortality directly related to the PTD procedure was 0.66% (1 patient).
      CONCLUSION: Percutaneous transhepatic biliary tract drainage requires a skilled
      radiologist who is able to manage all perioperative complications. At the same
      time, experienced medical staff are needed who are able to treat the drainage
      catheters correctly and are able to recognize severe complications in time.
      Complications after PTD occur also during home care of the patients; therefore,
      cooperation of home care nurses with hospitals where PTD is performed is
      therefore important. Catheter flushing should be included in the catalogue
      listing home care procedures.

PMID- 24891243
TI  - [Superficial thrombophlebitis of the lower limbs from the surgeons point of
      view].
AB  - INTRODUCTION: A new consensus on the management of superficial thrombophlebitis
      (STP) from the Central European Vascular Forum (CEVF) for the diagnosis and
      treatment of STP recommends anticoagulation treatment either with Fondaparinux
      2.5 mg for at least 45 days or with low molecular weight heparin (LMWH) for 4
      weeks in patients with thrombosis of GSV/SSV proven by duplex ultrasonography
      (DUS) and with thrombus length exceeding 5 cm. The dosage and duration of
      anticoagulation treatment depend on the associated diseases and other risk
      factors for TVE. Many options for doses an duration of treatment are referred to
      in the literature. Emergency surgery is not recommended. The aim of this study is
      to demonstrate the role of DUS examination in acute ascending thrombophlebitis
      (ASTP) of the GSV, and demonstrate the efficiency of surgical treatment -
      crossectomy and phlebectomy of thrombosed GSV/SSV. MATERIAL AND METHODS: The
      authors present their clinical experience with DUS diagnosis and surgical
      treatment of acute ascending thrombophlebitis in GSV/SSV on 66 patients with 68
      operations. In two of them bilateral crossectomy was performed. In the diagnosis
      it is necessary to perform DUS examination after clinical diagnosis of acute
      thrombophlebitis. It should be done bilaterally, not only in the affected limb.
      DUS confirms the measure, progression and eventually ascension of the thrombosis
      on the trunk of the GSV/SSV and perforating veins. Progress of the thrombotic
      process from the thigh to the SF/SP junction is usually a matter of a few hours.
      Daily ultrasound assessment should therefore be performed in acute
      thrombophlebitis, even during anticoagulation therapy. Thrombus near the SF/SP
      junction is a reason for urgent surgery - crossectomy and phlebectomy. RESULTS:
      66 patients were operated on under general anaesthesia without any complications.
      A large hematoma in the subinguinal region developed in one patient after
      surgery. A 50-year-old patient returned with colliquation of the residual
      varicose vein on the lower leg. Outpatient incision and evacuation had to be
      performed 3 weeks after surgery. Anticoagulation therapy with warfarin was
      started in two patients. The other patients were discharged 4 to 6 days following
      surgery without any problems. Post-operative anti-coagulation in other patients
      was not longer than 2 weeks. CONCLUSION: Urgent crossectomy and phlebectomy
      represent a reliable method of treatment in the management of acute ascending
      thrombophlebitis of GSV/SSV, guaranteeing prophylaxis of complications,
      especially in pregnant women with PT in the later phase of pregnancy. Surgical
      treatment destroys the damaged vein with crossectomy as a potential cause of deep
      vein thrombosis (DVT), pulmonary embolism (PE) and STP recurrence. After
      anticoagulation therapy the affected vein remains in situ. It can potentially
      cause the recurrence of STP, and DVT and PE may develop.

PMID- 24891242
TI  - [Dissection and coagulation technique in thyroid surgery - is it the key to a
      successful outcome?].
AB  - INTRODUCTION: This study analyzes the impact of coagulation instrument devices
      used during thyroid gland removal in which careful dissection and perfect
      haemostasis represent very important aspects. Standard electrocautery is compared
      to the use of bipolar forceps. The aim is to determine whether the use of
      different modes of coagulation is the key to the frequency and severity of
      postoperative complications following total thyroidectomy. MATERIAL AND METHODS:
      This study included 82 patients undergoing total thyroidectomy with haemostasis
      by conventional suture ligation technique combined with monopolar
      electrocauterization and 36 patients undergoing total thyroidectomy with complete
      haemostasis by bipolar forceps. The main outcomes measured were postoperative
      bleeding, recurrent laryngeal nerve palsy and post-thyroidectomy hypocalcaemia
      and hypoparathyroidism. Patients were followed up for 6 months. RESULTS: The
      results of our study showed that the use of bipolar forceps for vessel ligation
      in thyroid surgery is as safe and effective as the use of monopolar
      electrocautery and ligatures. Statistical analysis showed no significant
      differences in the rate of the individual postoperative complications between the
      two cohorts. Complication rates in the entire cohort were comparable with data
      reported in the literature. CONCLUSION: Both approaches are safe and reliable and
      both represent valid options. The choice might depend on the surgeons preferences
      and experience, the nature of the thyroid condition and the nature and extent of
      the surgical procedure.

PMID- 24891244
TI  - [Genetically determined thrombophilia as a cause of acute abdomen].
AB  - We report the case of a young patient with unknown, genetically caused
      thrombophilia in whom thrombosis of the main portal vein developed as well as of
      the hepatic branches and the superior mesenteric vein with necrosis of the small
      intestine. Partial resection of the small intestine was performed and
      conservative management of portal vein thrombosis with a therapeutic dose of LMWH
      was indicated. Key words: thrombophilia - thrombosis of the portal vein. 

PMID- 24891245
TI  - [Retroperitoneal neuroectodermal tumors].
AB  - Various types of neurogenous tumours occur in the retroperitoneum. Hormonally
      inactive tumours are often asymptomatic and their diagnosis is mostly accidental.
      Authors are presenting their recent experience with three cases. They discuss
      diagnostic options and the therapy of retroperitoneal schwannoma, ganglioneuroma
      and paraganglioma.

PMID- 24891246
TI  - [Importance of interdisciplinary cooperation in multiple trauma management].
AB  - Multiple trauma represents the most serious type of trauma in which the result of
      the treatment depends on the quality of pre-hospital care according to ATLS
      (Advanced Trauma Life Support) as well as on the availability of emergency
      specialized care in traumatology centres. Resuscitation in the early post-injury
      phase involves prevention of the lethal triad (hypothermia, acidosis,
      coagulopathy) development, as early as during pre-hospital care and also during
      admission to a traumatology department (damage control resuscitation). Damage
      control resuscitation involves permissive hypotension and coagulopathy correction
      with red blood cells (RBCs), fresh frozen plasma and platelets administration
      with crystalloid solutions restriction. Management in a traumatology centre
      involves : 1. Determining the sequence for treating each of the injuries step by
      step: a) control of external and intracavitary bleeding, b) operation for
      craniocerebral injuries, c) external fixation of fractures. 2. Phased management
      of intracavitary injuries (damage control surgery) and injuries of the
      extremities (damage control orthopaedics). 3. Non-operative management of solid
      organs injuries including radiointervention procedures. 4. Post-injury intensive
      care after the primary operation (treatment of the lethal triad). 5. Treatment
      regimen extension in craniocerebral injuries (stabilisation of cerebral perfusion
      pressure with sufficient oxygenation). 6. Modern therapeutic strategies in
      mechanical ventilation (protective, non-invasive ventilation). 7. Integration of
      new imaging methods such as MDCT (Multidetector Computed Tomography). Ensuring
      complex management in polytrauma treatment requires active cooperation of
      numerous clinical disciplines, already in the early post-injury period.

PMID- 24891247
TI  - [Multiple trauma - treatment of skeletal injuries with damage control
      orthopaedics].
AB  - New methods of treating seriously injured patients have been introduced in the
      field of trauma surgery since 1993. These consist mostly of differentiated and
      rapid procedures of treatment of the injured skeleton, with the aim of preventing
      the development of severe haemorrhagic shock and exsanguination of the patient.
      The precondition for introducing these techniques is the study of the organisms
      inflammatory response to trauma. Since 2000, this approach has been called damage
      control orthopaedics. The authors deal with the history of this method, the
      physiology of severe trauma, selection of patients eligible for this method and
      the appropriate timing of definitive treatment.

PMID- 24891248
TI  - [Pelvic fracture as part of multiple trauma].
AB  - A patient with pelvic injury, especially if the injury is part of multiple
      trauma, must be initially treated in accordance with the principles of Advanced
      Trauma Life Support(r). The authors define the indications of procedures
      corresponding to damage control surgery with regard to pelvic injury, and also to
      the timing of and performing the individual internal fixation techniques in
      pelvic fracture. A multidisciplinary approach with the individual treatment
      procedures reflecting the general condition of the injured patient is a key to
      favourable outcome.

PMID- 24891249
TI  - Research participation by people with intellectual disability and mental health
      issues: an examination of the processes of consent.
AB  - Balancing the demands of research and ethics is always challenging, and even more
      so when recruiting vulnerable groups. Within the context of current legislation
      and international human rights declarations, it is strongly advocated that
      research can and must be undertaken with all recipients of health-care services.
      Research in the field of intellectual disability presents particular challenges
      in regards to consenting processes. This paper is a reflective overview and
      analysis of the complex processes undertaken, and events that occurred in gaining
      informed consent from people with intellectual disability to participate in a
      study exploring their experiences of being an inpatient in mental health
      hospitals within Aotearoa/New Zealand. A framework based on capacity,
      information, and voluntariness is presented, with excerpts from the field
      provided to explore consenting processes. The practical implications of the
      processes utilized are then discussed in order to stimulate debate regarding
      clearer and enhanced methods of gaining informed consent from people with
      intellectual disability. 

PMID- 24891250
TI  - [Quality assurance in endoprosthetics].

PMID- 24891251
TI  - [Early detection of systematic defects by endoprostheses registries].
AB  - BACKGROUND: The burden of revision of the 210,000 total hip and the 146,000 total
      knee arthroplasties performed in Germany every year is 10.9% and 7.9%,
      respectively. Since the probability of revisions could be cut in half by the
      implementation of a national joint registry in Sweden, several other countries
      have also established national joint registries. Nevertheless, these registries
      were not able to detect the failure of some implant systems, which resulted in
      thousands of patients who had received implants being recalled later on.
      OBJECTIVES: We aimed to identify the methods that are currently used for
      statistical analyses in joint registries and which could be used to implement an
      early warning system. MATERIALS AND METHODS: We analyzed the available reports of
      national joint registries regarding the methods used for the early detection of
      implants that perform less efficiently than expected. The methods identified are
      described and evaluated if they are suitable for being used in a national joint
      registry. RESULTS: While most of the identified national joint registries use the
      Kaplan-Meier method for analyzing implant survival, there was little agreement
      regarding the methods used for the early detection of implants that perform less
      efficiently than expected. Methods identified included revision rate per 100
      component years, variants of statistical process control (SPC), cumulative sums
      (CUSUM) and funnel plots. CONCLUSION: Currently, there are no standardized
      methods for the early detection of inferior implants that are used by the
      established national joint registries. Most of the statistical methods that could
      be identified were either not used at all or only in a very limited number of
      registries. The value of these methods still needs to be established. It appears
      probable that the statistical methods for early detection have to be developed
      further in order to identify a possible inferior performance of implants at an
      earlier point in time. This is necessary in order to avoid that thousands of
      patients are again treated with implants which are associated with an increased
      revision rate.

PMID- 24891252
TI  - [Role of orthopedic rheumatologist in the therapy of rheumatic diseases with
      biologics].
AB  - The international strategies in the treatment of rheumatic diseases have changed
      dramatically in the last 10 years. In addition to the prescription of a basic
      medication as soon as possible, biologics are increasingly being used for drug
      treatment of rheumatic diseases in Germany. The domains of orthopedic surgeons
      and orthopedic rheumatologists are still the extended conservative and surgical
      treatment of inflammatory systemic diseases, which continue to play an important
      role despite the improved drug therapy options. Orthopedic surgeons should
      principally be familiar with the use of antirheumatic drugs, especially with
      respect to the perioperative management. However, there is also a role for the
      orthopedic surgeon in the early detection of inflammatory systemic diseases and
      in cooperation with rheumatologists in the medicinal treatment of selected
      diseases. Because patients with initial stages of joint pain, e.g. from
      rheumatoid arthritis (RA), spondyloarthritis (SpA) or psoriatic arthropathy often
      present first to an orthopedic surgeon, recognition of the early stages by the
      primary treating physician, including the necessary rapid induction of drug
      therapy is especially important. In addition there is a shortage of internist
      rheumatologists in Germany so that selective referral and close cooperation
      between the two physicians become of great importance. 

PMID- 24891253
TI  - Time-dependent bioaccumulation of distinct rod-type TiO2 nanoparticles:
      comparison by crystalline phase.
AB  - A complete understanding of the interaction between nanoparticles and biological
      systems, including nanoparticle uptake and distribution and the biological
      responses, could guide the design of safer and more effective nanoparticles than
      those currently available. In this study, we compared the distribution in mice
      over time of two rod-type titanium dioxide nanoparticles (TiNPs) that feature
      distinct phases, anatase (ATO) and brookite (BTO). Surface areas of BTO and ATO
      were estimated to be 102 and 268 m(2)  g(-1) , respectively, and negative charge
      on the surface of ATO was higher than that of BTO in deionized water. Both TiNPs
      were rapidly distributed into tissues after injection. At 4 weeks after
      injection, both TiNPs were maximally accumulated in the spleen, followed by the
      liver, but the total accumulation of ATO in tissues measured in this study was
      more than that of BTO. Moreover, the cellular antioxidant function was similar
      although the levels of Ti measured in tissues were distinct between the two
      TiNPs. Based on these results, we suggest that the fate of TiNPs in the body may
      differ according to the size and surface charge of the TiNPs even when their
      shape is the same.

PMID- 24891254
TI  - Incrementally increasing the length of a peptide backbone: effect on
      macrocyclisation efficiency.
AB  - Three novel analogues of the cyclic pentapeptide sansalvamide A have been
      synthesised in high yield. A leucine residue in the lead compound is replaced
      with either a glycine, beta-alanine or GABA residue, and the corresponding linear
      precursor peptides are found to cyclise with dramatically improved efficiency.
      This correlates with an increase in the effective molarity (EM) of the
      cyclisation reactions. 

PMID- 24891256
TI  - Assisted reproductive technologies: impact on fetal and neonatal outcomes.

PMID- 24891255
TI  - Diversification and asymmetrical gene flow across time and space: lineage sorting
      and hybridization in polytypic barking frogs.
AB  - Young species complexes that are widespread across ecologically disparate regions
      offer important insights into the process of speciation because of their
      relevance to how local adaptation and gene flow influence diversification. We
      used mitochondrial DNA and up to 28 152 genomewide single nucleotide
      polymorphisms from polytypic barking frogs (Craugastor augusti complex) to infer
      phylogenetic relationships and test for the signature of introgressive
      hybridization among diverging lineages. Our phylogenetic reconstructions suggest
      (i) a rapid Pliocene-Pleistocene radiation that produced at least nine distinct
      lineages and (ii) that geographic features of the arid Central Mexican Plateau
      contributed to two independent northward expansions. Despite clear lineage
      differentiation (many private alleles and high between-lineage FST scores), D
      statistic tests, which differentiate introgression from ancestral polymorphism,
      allowed us to identify two putative instances of reticulate gene flow.
      Partitioned D-statistics provided evidence that these events occurred in the same
      direction between clades but at different points in time. After correcting for
      geographic distance, we found that lineages involved in hybrid gene flow
      interactions had higher levels of genetic variation than independently evolving
      lineages. These findings suggest that the nature of hybrid compatibility can be
      conserved overlong periods of evolutionary time and that hybridization between
      diverging lineages may contribute to standing levels of genetic variation. 

PMID- 24891257
TI  - Staged Bentall procedure and extra-anatomical repair of coarctation of aorta.

PMID- 24891258
TI  - Expression of skin color genes in lymphocytes of Karan Fries cattle and seasonal
      relationship with tyrosinase and cortisol.
AB  - To evaluate difference in the expression of skin color genes (melanocortin 1
      receptor (MC1R) and premelanosome (PMEL)) in lymphocytes during winter and summer
      season and their correlation with tyrosinase enzyme and cortisol, ten Karan-Fries
      heifers were selected from National Dairy Research Institute (NDRI) cattle farm.
      Blood samples were collected from the animals during winter (THI = 60) and summer
      (THI = 83) season at weekly intervals. Relative MC1R and PMEL messenger RNA
      (mRNA) expression of Karan Fries cattle was found to be significantly (P < 0.01)
      higher during winter than summer. Similarly, tyrosinase activity during winter
      was found to be significantly (P < 0.01) higher than summer season. However,
      plasma cortisol level was significantly (P < 0.01) higher during summer than
      winter. Thus, expression of the skin color genes showed positive correlation with
      tyrosinase enzyme, but negative correlation with cortisol level. Expression of
      MC1R and PMEL in lymphocytes and tyrosinase activity of Karan Fries cattle was
      highly reduced during summer. The present study showed that the ability of Karan
      Fries cattle to protect themselves from the harmful radiation of sunlight by
      melanization decreased with increased heat stress on them.

PMID- 24891259
TI  - Activity recommendations for anticoagulated patients may differ, but should be
      based on accurate data interpretation.

PMID- 24891260
TI  - Quantitative analysis of mitral annular geometry and function in healthy
      volunteers using transthoracic three-dimensional echocardiography.
AB  - BACKGROUND: Quantitative assessment of the mitral annulus provides information
      regarding the pathophysiology of mitral regurgitation and aids in the planning of
      reparative surgery. Three-dimensional (3D) transthoracic echocardiographic data
      sets acquired with current scanners have enough spatial and temporal resolution
      to allow the quantitative analysis of the mitral annulus. Accordingly, the
      authors performed (1) a validation study to assess the agreement of quantitative
      analysis of the mitral annulus performed on 3D transthoracic echocardiography
      (TTE) and 3D transesophageal echocardiography (TEE) and (2) a normative study to
      obtain the reference values of 3D transthoracic echocardiographic parameters for
      mitral annular (MA) geometry and dynamics. METHODS: Mitral valve data sets were
      obtained by 3D TEE and 3D TTE in 30 consecutive patients with clinically
      indicated TEE (validation study) and 3D TTE in 224 healthy volunteers (aged 18-76
      years) (normative study). RESULTS: In the validation study, MA measurements
      obtained by 3D TTE were similar to those obtained by 3D TEE (P = NS). In the
      normative study, MA analysis by 3D TTE was feasible (94.5%) and reproducible
      (intraclass correlation coefficient = 0.78-0.97). MA diameters, area, and
      circumference were correlated with body surface area (r > 0.50 for all) but not
      with age. Men had larger MA areas than women (4.9 +/- 1.0 vs 4.5 +/- 0.7
      cm(2)/m(2), P = .004). During systole, MA area decreased by 29 +/- 5%. This
      decrease was related mainly to anteroposterior diameter shortening (20 +/- 7%).
      CONCLUSIONS: MA quantitative analysis by 3D TTE was accurate compared with 3D TEE
      in unselected patients with mitral valve disease. In healthy subjects, it was
      highly feasible and reproducible. The availability of reference values for MA
      geometry and dynamics may foster the implementation of MA quantitative analysis
      by 3D TTE in clinical settings.

PMID- 24891262
TI  - Transient repolarization alterations dominate the initial phase of an acute
      anterior infarction--a vectorcardiography study.
AB  - OBJECTIVE: To study effects of ischemia-reperfusion on ventricular
      electrophysiology in humans by three-dimensional electrocardiography. METHODS:
      Fifty-seven patients with first-time acute anterior ST elevation myocardial
      infarction were monitored from admission and >24h after symptom onset with
      continuous vectorcardiography (VCG; modified Frank orthogonal leads). Global
      ventricular depolarization and repolarization (VR) measures were compared at
      maximum vs. minimum ST vector magnitude (STVM) (median 208; 111-303 vs. 362; 165
      1359min after symptom onset). RESULTS: At maximum vs. minimum STVM the Tarea
      (overall VR dispersion) almost tripled (118 vs. 41MUVs; p<0.0001), the T-loop
      bulginess was 90% greater (Tavplan 0.91 vs 0.48MUV; p<0.0001), and Tpeak-end/QT
      was 39% larger (0.32 vs 0.23; p<0.0001). QRSarea (overall dispersion of
      depolarization) was 12% larger at maximum STVM, while QRS duration was 10% longer
      at minimum STVM. CONCLUSIONS: Ischemia-reperfusion was accompanied by profound
      and transient alterations of VR dispersion, while changes in depolarization were
      modest and delayed.

PMID- 24891261
TI  - Reproducibility of regional and global longitudinal strains derived from two
      dimensional speckle-tracking and doppler tissue imaging between expert and novice
      readers during quantitative dobutamine stress echocardiography.
AB  - BACKGROUND: Longitudinal strain (LS) is a quantitative parameter that adds
      incremental value to wall motion analysis. The aim of this study was to compare
      the reproducibility of LS derived from Doppler tissue imaging and speckle
      tracking between an expert and a novice strain reader during dobutamine stress
      echocardiography (DSE). METHODS: Forty-one patients (mean age, 65 +/- 15 years;
      mean ejection fraction, 58 +/- 11%) underwent DSE per clinical protocol. Global
      LS derived from speckle-tracking and regional LS derived from both speckle
      tracking and Doppler tissue imaging were measured twice by an expert strain
      reader and also measured twice by a novice strain reader. Intraobserver and
      interobserver analyses were performed using intraclass correlation coefficients
      (ICC), Bland-Altman analysis, and absolute difference values (mean +/- SD).
      RESULTS: Global LS measured by the expert strain reader demonstrated high
      intraobserver measurement reproducibility (rest: ICC = 0.95, absolute difference
      = 5.5 +/- 4.9%; low dose: ICC = 0.96, absolute difference = 5.7 +/- 3.7%; peak
      dose: ICC = 0.87, absolute difference = 11.4 +/- 8.4%). Global LS measured by the
      novice strain reader also demonstrated high intraobserver reproducibility (rest:
      ICC = 0.97, absolute difference = 4.1 +/- 3.4%; low dose: ICC = 0.94, absolute
      difference = 5.4 +/- 5.9%; peak dose: ICC = 0.94, absolute difference = 6.1 +/-
      4.8%). Global LS also showed high interobserver agreement between the expert and
      novice readers at all stages of DSE (rest: ICC = 0.90, absolute difference = 8.5
      +/- 7.5%; low dose: ICC = 0.90, absolute difference = 8.9 +/- 7.1%; peak dose:
      ICC = 0.87, absolute difference = 10.8 +/- 8.4%). Of all parameters studied, LS
      derived from Doppler tissue imaging had relatively low interobserver and
      intraobserver agreement. CONCLUSIONS: Global LS is highly reproducible during all
      stages of DSE. This variable is a potentially reliable and reproducible measure
      of myocardial deformation.

PMID- 24891263
TI  - Steps required to inclusion in commercial ECG analysis systems--the new ECG
      indices for quantitating extent, acuteness and severity of acute myocardial
      ischemia for facilitating emergency triage decisions.
AB  - Clinically useful diagnostic methods for chest pain triage often fail to reach
      everyday practice where they can improve patient outcomes. One means to bridge
      the gap is through adoption of ECG interpretive algorithms with enhanced accuracy
      or expanded features into established commercial products. The transition from
      innovation to industry can be facilitated if researchers consider three factors
      aiding a successful handoff to companies. First, they should assess their
      algorithm to assure that it meets a real market need and can be easily
      assimilated by commercial partners. Second, their design documentation and
      databases should support the regulated development processes required of
      manufacturers. Finally, they should hold appropriate expectations for the
      structure of commercial partnerships that lead to release of a marketed product. 

PMID- 24891264
TI  - True Brugada pattern or only high V1-V2 electrode placement?

PMID- 24891265
TI  - Imaging QRS complex and ST segment in myocardial infarction.
AB  - BACKGROUND: Acute myocardial infarction creates regions of altered electrical
      properties of myocardium resulting in typical QRS patterns (pathological Q waves)
      and ST segment deviations observed in leads related to the MI location. The aim
      of this study was to present a graphical method for imaging the changes in the
      sequence of depolarization and the ST segment deviations in myocardial infarction
      using the Dipolar ElectroCARdioTOpography (DECARTO) method. MATERIAL AND METHODS:
      Simulated ECG data corresponding to intramural, electrically inactive areas
      encircled by transmural areas with slowed impulse propagation velocity in
      anteroseptal and inferior locations were used for imaging the altered sequence of
      depolarization and the ST vector. The ECGs were transformed to areas projected on
      the image surface so as to image the process of ventricular depolarization based
      on the orientation and magnitude of the instantaneous QRS vectors, and the
      estimated "myocardium at risk" based on the ST segment deviation. RESULTS: The
      images are presented as Mercator projections with the texture of anatomical
      segments of the heart and the corresponding coronary artery distribution. The
      changes in depolarization sequence were visible as dislocations of activated
      areas circumventing the affected areas, while the "myocardium at risk" estimated
      from the ST segment deviation pointed to the affected area. CONCLUSION: The
      presented method of imaging ECG allows visualizing changes in sequence of
      depolarization as well as the ST segment deviations in myocardial infarction and
      they can be visually compared with non-ECG imaging methods.

PMID- 24891266
TI  - Transient post-reperfusion left bundle branch block and accelerated
      idioventricular rhythm with paradoxical QRS narrowing.
AB  - Accelerated idioventricular rhythm (AIVR) commonly follows coronary reperfusion
      and has been called a "reperfusion arrhythmia". Transient left bundle branch
      block (LBBB) is only rarely seen after interventional reperfusion and is usually
      considered a procedural complication. We report herein electrocardiograms (ECGs)
      in a case of acute lateral myocardial infarction which demonstrate both post
      perfusion AIVR and a simultaneous transient LBBB with fusion complexes causing
      paradoxical QRS narrowing. 

PMID- 24891267
TI  - Assessment of mean respiratory rate from ECG recordings for risk stratification
      after myocardial infarction.
AB  - BACKGROUND: We recently reported that nocturnal respiratory rate (NRR) predicts
      non-sudden cardiac death in survivors of myocardial infarction (MI). Here, we
      present the details of the technique deriving NRR from ECG recordings. METHODS:
      Continuous ECG and respiratory chest excursions were simultaneously recorded in
      941 MI survivors who were followed-up for 5-years. Mean respiratory rate was
      derived from the ECG based on RR intervals, QRS amplitudes, and QRS vectors and
      compared to chest belt measurements. NRR was calculated from Holter-ECGs
      accordingly using the same ECG processing. RESULTS: Directly-measured and ECG
      derived respiratory rates were in good agreement. Areas under the ROC curve for
      10-min-ECG- and Holter-derived respiratory rate were well in the confidence
      intervals of that of the chest belt measurement. The optimum dichotomy of NRR for
      the prediction of mortality was >=18.6 breaths per minute. CONCLUSIONS: The mean
      respiratory rate can be precisely derived from continuous ECGs.

PMID- 24891268
TI  - T wave inversions in leads with ST elevations in patients with acute anterior ST
      elevation myocardial infarction is associated with patency of the infarct related
      artery.
AB  - OBJECTIVES: Following reperfusion therapy, early T wave inversions (TWI) have
      been shown to be a marker of successful reperfusion. We aimed to evaluate the
      relationship of TWI on the presenting ECG with spontaneous reperfusion as
      assessed by coronary angiography in patients with ST elevation (STE) myocardial
      infarction (STEMI). METHODS: Data of 146 consecutive patients presenting to the
      St. Luke's Episcopal Hospital Emergency Department with acute STEMI undergoing
      primary percutaneous coronary intervention (p-PCI) between January, 2007 and
      October, 2010 were retrospectively analyzed. Clinical data, ECG and angiographic
      data were reviewed. Patients were dichotomized based on T wave morphology on the
      presenting ECG into 2 groups - those with TWI and those with positive T waves
      (PTW). RESULTS: Thirty-one patients (21.2%) had TWI, while 115 (78.8%) had PTW.
      Sixty-four (43.8%) patients had anterior STE and 75 (51.3%) had inferior STE.
      Anterior STE was more likely to have TWI than non-anterior (29.7% vs. 14.6;
      p=0.014). By angiography, infarct related artery (IRA) patency (TIMI 2-3 flow)
      was seen in 45 (30.8%). TWI was more likely to be associated with IRA patency
      compared to PTW (51.6% vs. 25.2%; p=0.008). In patients with anterior STEMI and
      TWI, patent IRA was seen more frequently compared to those with PTW (68.4% vs.
      20%; p<0.001). There was no association of T wave morphology and TIMI flow in
      patients with non-anterior STEMI. Patients presenting with stuttering symptoms
      were more likely to have TWI (70.4% vs. 10.2%; p <0.001) suggesting recurrent
      episodes of reperfusion and ischemia. CONCLUSIONS: In anterior STEMI patients,
      TWI on the presenting ECG is associated with spontaneous reperfusion. This
      relationship was not found among patients with non-anterior STEMI.

PMID- 24891269
TI  - Weight loss intervention trials in women with breast cancer: a systematic review.
AB  - Obesity has been associated with poor health outcomes in breast cancer survivors.
      Thus, weight loss is recommended for overweight and obese survivors. We
      systematically reviewed studies (published up to July 2013) that evaluated
      behaviourally based, weight loss interventions in women with breast cancer
      exclusively. Completed randomized trials, single-arm trials and ongoing trials
      were reviewed. Within-group and between-group differences for weight loss were
      extracted, as was data on secondary outcomes, i.e. clinical biomarkers, patient
      reported outcomes, adverse events. Ten completed randomized trials, four single
      arm trials and five ongoing trials were identified. Statistically significant
      within-group weight loss was observed over periods of 2 to 18 months in 13 of the
      14 trials, with six randomized and two single-arm trials observing mean weight
      loss >=5%. Clinical biomarkers, psychosocial and patient-reported outcomes were
      measured in a small number of studies. No serious adverse events were reported.
      Only two trials assessed maintenance of intervention effects after the end-of
      intervention and none reported on cost-effectiveness. The studies included in
      this review suggest that weight loss is feasible to achieve and is safe in women
      following treatment for breast cancer. Future studies should assess (and be
      powered for) a range of biomarker and patient-reported outcomes, and be designed
      to inform translation into practice. 

PMID- 24891270
TI  - Synthesis and antisense properties of 2'-O-(2S-methoxypropyl)-RNA-modified gapmer
      antisense oligonucleotides.
AB  - To ascertain whether increasing hydrophobicity can enhance the activity of second
      generation antisense oligonucleotides (ASOs) in muscle, we investigated the
      antisense properties of 2'-O-(2S-methoxypropyl)-RNA (2S-MOP)-modified ASOs.
      Synthesis of the 2S-MOP 5-methyl uridine phosphoramidite was accomplished on a
      multi-gram scale by Lewis-acid-catalyzed ring opening of 5'-O-tert
      butyldiphenylsilyl ether-protected 2,2'-anhydro-5-methyl uridine with 2S-methoxy
      1-propanol. Synthesis of the 2S-MOP 5-methyl cytidine nucleoside from the
      corresponding 5-methyl uridine nucleoside was accomplished by formation and
      displacement of a 4-triazolide intermediate with aqueous ammonia. 2S-MOP-modified
      oligonucleotides were prepared on an automated DNA synthesizer and showed similar
      enhancements in duplex thermal stability as 2'-O-methoxyethyl RNA (MOE)-modified
      oligonucleotides. 2S-MOP-containing antisense oligonucleotides were evaluated in
      Balb-c mice and showed good activity for decreasing the expression levels of
      scavenger receptor B1 (Srb1) and phosphatase and tensin homologue (PTEN) mRNA in
      liver and muscle tissue.

PMID- 24891271
TI  - Impact of pacing site on QRS duration and its relationship to hemodynamic
      response in cardiac resynchronization therapy for congestive heart failure.
AB  - INTRODUCTION: Recent studies have demonstrated that left ventricular (LV) pacing
      site is a critical parameter in optimizing cardiac resynchronization therapy
      (CRT). The present study evaluates the effect of pacing from different LV
      locations on QRS duration (QRSd) and their relationship to acute hemodynamic
      response in congestive heart failure patients. METHODS AND RESULTS: Thirty-five
      patients with nonischemic dilated cardiomyopathy and left bundle branch block
      referred for CRT device implantation were studied. Eleven predetermined LV pacing
      sites were systematically assessed in random order: epicardial: coronary sinus
      (CS); endocardial: basal and mid-cavity (septal, anterior, lateral, and
      inferior), apex, and the endocardial site facing the CS pacing site. For each
      patient QRSd and +dP/dtmax during baseline (AAI) and DDD LV pacing at 2
      atrioventricular delays were compared. Response to CRT was significantly better
      in patients with wider baseline QRSd (>=150 milliseconds). Hemodynamic response
      was inversely correlated to increase of QRSd during LV pacing (short
      atrioventricular [AV] delay: r = 0.44, P < 0.001; long AV delay: r = 0.59, P <
      0.001). Compared to baseline, LV pacing at the site of shortest QRSd
      significantly improved +dP/dtmax (+18 +/- 25%, P < 0.001) but was not superior to
      other conventional strategy (lateral wall, CS pacing, and echo-guided) and was
      inferior to a hemodynamically guided strategy. CONCLUSIONS: In our study, we have
      demonstrated that changes of QRSd during LV pacing correlated with acute
      hemodynamic response and that LV pacing location was a primary determinant of
      paced QRSd. Although QRSd did not predict the maximum hemodynamic response, our
      results confirm the link between electrical activation and hemodynamic response
      of the LV during CRT.

PMID- 24891272
TI  - Dialysis facility and network factors associated with low kidney transplantation
      rates among United States dialysis facilities.
AB  - Variability in transplant rates between different dialysis units has been noted,
      yet little is known about facility-level factors associated with low standardized
      transplant ratios (STRs) across the United States End-stage Renal Disease (ESRD)
      Network regions. We analyzed Centers for Medicare & Medicaid Services Dialysis
      Facility Report data from 2007 to 2010 to examine facility-level factors
      associated with low STRs using multivariable mixed models. Among 4098 dialysis
      facilities treating 305 698 patients, there was wide variability in facility
      level STRs across the 18 ESRD Networks. Four-year average STRs ranged from 0.69
      (95% confidence interval [CI]: 0.64-0.73) in Network 6 (Southeastern Kidney
      Council) to 1.61 (95% CI: 1.47-1.76) in Network 1 (New England). Factors
      significantly associated with a lower STR (p < 0.0001) included for-profit
      status, facilities with higher percentage black patients, patients with no health
      insurance and patients with diabetes. A greater number of facility staff, more
      transplant centers per 10 000 ESRD patients and a higher percentage of patients
      who were employed or utilized peritoneal dialysis were associated with higher
      STRs. The lowest performing dialysis facilities were in the Southeastern United
      States. Understanding the modifiable facility-level factors associated with low
      transplant rates may inform interventions to improve access to transplantation. 

PMID- 24891273
TI  - Transoral laser microsurgery +/- adjuvant therapy versus chemoradiotherapy for
      stage III and IVA oropharyngeal squamous cell carcinoma: Preliminary comparison
      of early swallowing outcomes.
AB  - BACKGROUND: Observational data suggests transoral surgery may offer benefit in
      swallowing over chemoradiotherapy. METHODS: In this preliminary, non-randomized
      study, patients with stage III and IVA oropharyngeal carcinoma treated with
      transoral laser microsurgery (TLM) were assessed pretreatment and 3 months after
      treatment using the MD Anderson Dysphagia Inventory (MDADI), the Performance
      Status Scale (PSS), and a timed Water Swallow Test (WST). Comparisons were made
      with a historical chemoradiotherapy (CRT) cohort. RESULTS: Based on patients with
      measurements at both times, the decrease in score between baseline and 3 months
      was greater for CRT patients (n = 26-28) than for TLM (n = 20-21) patients for
      each of MDADI, PSS, and WST. A repeated measures analysis that looked at all 3
      scores simultaneously and allowed for missing values gave mostly similar results
      (except for MDADI). CONCLUSION: TLM was associated with good early swallowing
      outcomes at 3 months and may offer a benefit over CRT. The results should be
      viewed as preliminary data, providing useful reference for any proposed
      controlled trial.

PMID- 24891275
TI  - Significance of research networking for enhancing collaboration and research
      productivity.

PMID- 24891276
TI  - Challenges in life sciences and health systems in the 21st century.

PMID- 24891274
TI  - A therapeutic trial of decitabine and vorinostat in combination with chemotherapy
      for relapsed/refractory acute lymphoblastic leukemia.
AB  - DNA hypermethylation and histone deacetylation are pathways of leukemia
      resistance. We investigated the tolerability and efficacy of decitabine and
      vorinostat plus chemotherapy in relapse/refractory acute lymphoblastic leukemia
      (ALL). Decitabine (15 mg/m(2) iv) and vorinostat (230 mg/m(2) PO div BID) were
      given days 1-4 followed by vincristine, prednisone, PEG-asparaginase, and
      doxorubicin. Genome wide methylation profiles were performed in 8 matched patient
      bone marrow (BM) samples taken at day 0 and day 5 (postdecitabine). The median
      age was 16 (range, 3-54) years. All patients had a prior BM relapse, with five
      relapsing after allogeneic transplant. The most common nonhematological
      toxicities possibly related to decitabine or vorinostat were infection with
      neutropenia (grade 3; n = 4) and fever/neutropenia (grade 3, n = 4; grade 4, n =
      1). Of the 13 eligible patients, four achieved complete remission without
      platelet recovery (CRp), two partial response (PR), one stable disease (SD), one
      progressive disease (PD), two deaths on study and three patients who did not have
      end of therapy disease evaluations for an overall response rate of 46.2% (CRp +
      PR). Following decitabine, significant genome-wide hypo-methylation was observed.
      Comparison of clinical responders with nonresponders identified methylation
      profiles of clinical and biological relevance. Decitabine and vorinostat followed
      by re-Induction chemotherapy was tolerable and demonstrated clinical benefit in
      relapsed patients with ALL. Methylation differences were identified between
      responders and nonresponders indicating interpatient variation, which could
      impact clinical outcome. This study was registered at www.clinicaltrials.gov as
      NCT00882206.

PMID- 24891277
TI  - Visualization of melanoma tumor with lectin-conjugated rare-earth doped fluoride
      nanocrystals.
AB  - AIM: To develop specific fluorescent markers for melanoma tumor visualization,
      which would provide high selectivity and reversible binding pattern, by the use
      of carbohydrate-recognizing proteins, lectins, combined with the physical ability
      for imaging deep in the living tissues by utilizing red and near infrared
      fluorescent properties of specific rare-earth doped nanocrystals (NC). METHODS:
      B10F16 melanoma cells were inoculated to C57BL/6 mice for inducing experimental
      melanoma tumor. Tumors were removed and analyzed by lectin-histochemistry using
      LABA, PFA, PNA, HPA, SNA, GNA, and NPL lectins and stained with hematoxylin and
      eosin. NPL lectin was conjugated to fluorescent NaGdF4:Eu(3+)-COOH nanoparticles
      (5 nm) via zero length cross-linking reaction, and the conjugates were purified
      from unbound substances and then used for further visualization of histological
      samples. Fluorescent microscopy was used to visualize NPL-NaGdF4:Eu(3+) with the
      fluorescent emission at 600-720 nm range. RESULTS: NPL lectin selectively
      recognized regions of undifferentiated melanoblasts surrounding neoangiogenic
      foci inside melanoma tumor, PNA lectin recognized differentiated melanoblasts,
      and LCA and WGA were bound to tumor stroma regions. NPL-NaGdF4:Eu(3+) conjugated
      NC were efficiently detecting newly formed regions of melanoma tumor, confirmed
      by fluorescent microscopy in visible and near infrared mode. These conjugates
      possessed high photostability and were compatible with convenient xylene-based
      mounting systems and preserved intensive fluorescent signal at samples storage
      for at least 6 months. CONCLUSION: NPL lectin-NaGdF4:Eu(3+) conjugated NC
      permitted distinct identification of contours of the melanoma tissue on
      histological sections using red excitation at 590-610 nm and near infrared
      emission of 700-720 nm. These data are of potential practical significance for
      development of glycans-conjugated nanoparticles to be used for in vivo
      visualization of melanoma tumor.

PMID- 24891278
TI  - A comparative study of neurotoxic potential of synthesized polysaccharide-coated
      and native ferritin-based magnetic nanoparticles.
AB  - AIM: To analyze the neurotoxic potential of synthesized magnetite nanoparticles
      coated by dextran, hydroxyethyl starch, oxidized hydroxyethyl starch, and
      chitosan, and magnetic nanoparticles combined with ferritin as a native protein.
      METHODS: The size of nanoparticles was analyzed using photon correlation
      spectroscopy, their effects on the conductance of planar lipid membrane by planar
      lipid bilayer technique, membrane potential and acidification of synaptic
      vesicles by spectrofluorimetry, and glutamate uptake and ambient level of
      glutamate in isolated rat brain nerve terminals (synaptosomes) by radiolabeled
      assay. RESULTS: Uncoated synthesized magnetite nanoparticles and nanoparticles
      coated by different polysaccharides had no significant effect on synaptic vesicle
      acidification, the initial velocity of L-[(14)C]glutamate uptake, ambient level
      of L-[(14)C]glutamate and the potential of the plasma membrane of synaptosomes,
      and conductance of planar lipid membrane. Native ferritin-based magnetic
      nanoparticles had no effect on the membrane potential but significantly reduced L
      [(14)C]glutamate transport in synaptosomes and acidification of synaptic
      vesicles. CONCLUSIONS: Our study indicates that synthesized magnetite
      nanoparticles in contrast to ferritin have no effects on the functional state and
      glutamate transport of nerve terminals, and so ferritin cannot be used as a
      prototype, analogue, or model of polysaccharide-coated magnetic nanoparticle in
      toxicity risk assessment and manipulation of nerve terminals by external magnetic
      fields. Still, the ability of ferritin to change the functional state of nerve
      terminals in combination with its magnetic properties suggests its
      biotechnological potential.

PMID- 24891279
TI  - Specific antioxidant compounds differentially modulate cytotoxic activity of
      doxorubicin and cisplatin: in vitro and in vivo study.
AB  - AIM: To use the antioxidant compounds (sodium selenite, selenomethionine, D
      pantethine) for modulation of cytotoxic effect of doxorubicin and cisplatin
      toward wild type and drug-resistant mutants of several human tumor cells. Similar
      treatments were applied in vivo toward adult male Wistar rats. METHODS: Human
      tumor cells of different lines (HCT-116, Jurkat and HL-60) with various
      mechanisms of drug-resistance were treated with doxorubicin or cisplatin, alone
      or in combination with sodium selenite, selenomethionine, or D-pantethine. Cell
      viability, induction of apoptosis, and production of O2- radicals were measured.
      Activity of redox potential modulating enzymes was measured in the liver and
      blood plasma of adult male Wistar rats subjected to similar treatments. RESULTS:
      All antioxidants used in physiologically harmless concentration inhibited
      cytotoxic action of doxorubicin toward tumor cells sensitive to chemotherapy
      treatment by 15%-30%, and slightly enhanced cytotoxic effect of this medicine
      toward drug-resistant malignant cells. At the same time, there was no significant
      effect of these antioxidants on cisplatin action. Such effects were accompanied
      by a complete inhibition of production of superoxide radicals induced by
      doxorubicin. The results of in vivo study in adult male Wistar rats were in
      agreement with the results of in vitro study of human tumor cells. CONCLUSION:
      Protective effect of specific antioxidant agents during cytotoxic action of
      doxorubicin was demonstrated in vitro in drug-sensitive human tumor cells and in
      adult male Wistar rats, while there was no protective effect in drug-resistant
      sub-lines of these tumor cells during action of doxorubicin and cisplatin.

PMID- 24891280
TI  - Impact of ovariectomy, high fat diet, and lifestyle modifications on
      oxidative/antioxidative status in the rat liver.
AB  - AIM: To estimate the impact of high fat diet and estrogen deficiency on the
      oxidative and antioxidative status in the liver of the ovariectomized rats, as
      well as the ameliorating effect of physical activity or consumption of functional
      food containing bioactive compounds with antioxidative properties on oxidative
      damage in the rat liver. METHODS: The study was conducted from November 2012 to
      April 2013. Liver oxidative damage was determined by lipid peroxidation levels
      expressed in terms of thiobarbituric acid reactive substances (TBARS), while
      liver antioxidative status was determined by catalase (CAT), glutathione
      peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR)
      activities, and glutathione (GSH) content. Sixty-four female Wistar rats were
      divided into eight groups: sham operated and ovariectomized rats that received
      either standard diet, high fat diet, or high fat diet supplemented with cereal
      selenized onion biscuits or high fat diet together with introduction of physical
      exercise of animals. RESULTS: High fat diet significantly increased TBARS content
      in the liver compared to standard diet (P=0.032, P=0.030). Furthermore, high fat
      diet decreased the activities of CAT, GR, and GST, as well as the content of GSH
      (P<0.050). GPx activity remained unchanged in all groups. Physical activity and
      consumption of cereal selenized onion biscuits showed protective effect through
      increased GR activity in sham operated rats (P=0.026, P=0.009), while in
      ovariectomized group CAT activity was increased (P=0.018) in rats that received
      cereal selenized onion biscuits. CONCLUSION: Feeding rats with high fat diet was
      accompanied by decreased antioxidative enzyme activities and increased lipid
      peroxidation. Bioactive compounds of cereal selenized onion biscuits showed
      potential to attenuate the adverse impact of high fat diet on antioxidative
      status.

PMID- 24891281
TI  - Effects of high fat diet, ovariectomy, and physical activity on leptin receptor
      expression in rat brain and white fat tissue.
AB  - AIM: To evaluate in a rat animal model whether ovariectomy, high fat diet (HFD),
      and physical activity in the form of running affect leptin receptor (Ob-R)
      distribution in the brain and white fat tissue compared to sham (Sh) surgery,
      standard diet (StD), and sedentary conditions. METHODS: The study included 48
      female laboratory Wistar rats (4 weeks old). Following eight weeks of feeding
      with standard or HFD, rats were subjected to either OVX or Sh surgery. After
      surgery, all animals continued StD or HFD for the next 10 weeks. During these 10
      weeks, ovariectomy and Sh groups were subjected to physical activity or sedentary
      conditions. Free-floating immunohistochemistry and Western blot methods were
      carried out to detect Ob-R in the brain and adipose tissue. RESULTS: StD
      ovariectomy-sedentary group had a greater number of Ob-R positive neurons in
      lateral hypothalamic nuclei than StD-Sh-sedentary group. There was no difference
      in Ob-R positive neurons in arcuatus nuclei between all groups. Ob-R distribution
      in the barrel cortex was higher in HFD group than in StD group. Ob-R presence in
      perirenal and subcutaneous fat was decreased in StD-ovariectomy group.
      CONCLUSION: HFD and ovariectomy increased Ob-R distribution in lateral
      hypothalamic nuclei, but there was no effect on arcuatus nuclei. Our results are
      first to suggest that HFD, ovariectomy, and physical activity affect Ob-R
      distribution in the barrel cortex, which might be correlated with the role of Ob
      R in election of food in rats.

PMID- 24891283
TI  - Perinatal hypoxia: different effects of the inhibitors of GABA transporters GAT1
      and GAT3 on the initial velocity of [3H]GABA uptake by cortical, hippocampal, and
      thalamic nerve terminals.
AB  - AIM. To analyze the effects of highly selective blocker GAT1, NO-711, and
      substrate inhibitor GAT3, beta-alanine, on the initial velocity of [(3)H]GABA
      uptake by cortical, hippocampal, and thalamic nerve terminals (synaptosomes)
      after perinatal hypoxia. METHODS. Animals were divided into two groups: control
      (n=17) and hypoxia (n=12). Rats in the hypoxia group underwent hypoxia and
      seizures (airtight chamber, 4% O2 and 96% N2) at the age of 10-12 postnatal days
      and were used in the experiments 8-9 weeks after hypoxia. RESULTS. In cortical
      synaptosomes, the effects of NO-711 (30 MUMU) and beta-alanine (100 MUMU) on
      [(3)H]GABA uptake were similar in control and hypoxia groups. In hippocampal
      synaptosomes, NO-711 inhibited 84.3% of the initial velocity of [(3)H]GABA uptake
      in normal conditions and 80.1% after hypoxia, whereas the effect of beta-alanine
      was increased after hypoxia from 14.4% to 22.1%. In thalamic synaptosomes, the
      effect of NO-711 was decreased by 79.6% in controls and by 70.9% in hypoxia
      group, whereas the effect of beta-alanine was increased after hypoxia from 20.2%
      to 30.2%. CONCLUSIONS. The effectiveness of beta-alanine to influence GABA uptake
      was increased in hippocampal and thalamic nerve terminals as a result of
      perinatal hypoxia and the effectiveness of NO-711 in thalamic nerve terminals was
      decreased. These results may indicate changes in the ratio of active GAT1/GAT3
      expressed in the plasma membrane of nerve terminals after perinatal hypoxia. We
      showed a possibility to modulate non-GAT1 GABA transporter activity in different
      brain regions by exogenous and endogenous beta-alanine.

PMID- 24891282
TI  - Single acute stress-induced progesterone and ovariectomy alter cardiomyocyte
      contractile function in female rats.
AB  - AIM: To assess how ovarian-derived sex hormones (in particular progesterone)
      modify the effects of single acute stress on the mechanical and biochemical
      properties of left ventricular cardiomyocytes in the rat. METHODS: Non
      ovariectomized (control, n=8) and ovariectomized (OVX, n=8) female rats were kept
      under normal conditions or were exposed to stress (control-S, n=8 and OVX-S,
      n=8). Serum progesterone levels were measured using a chemiluminescent
      immunoassay. Left ventricular myocardial samples were used for isometric force
      measurements and protein analysis. Ca(2+)-dependent active force (Factive),
      Ca(2+)-independent passive force (Fpassive), and Ca(2+)-sensitivity of force
      production were determined in single, mechanically isolated, permeabilized
      cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament
      proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were
      analyzed by sodium dodecyl sulfate gel electrophoresis using protein and
      phosphoprotein stainings. RESULTS: Serum progesterone levels were significantly
      increased in stressed rats (control-S, 35.6+/-4.8 ng/mL and OVX-S, 21.9+/-4.0
      ng/mL) compared to control (10+/-2.9 ng/mL) and OVX (2.8+/-0.5 ng/mL) groups.
      Factive was higher in the OVX groups (OVX, 25.9+/-3.4 kN/m(2) and OVX-S, 26.3+/
      3.0 kN/m(2)) than in control groups (control, 16.4+/-1.2 kN/m(2) and control-S,
      14.4+/-0.9 kN/m(2)). Regarding the potential molecular mechanisms, Factive
      correlated with MyBP-C phosphorylation, while myofilament Ca(2+)-sensitivity
      inversely correlated with serum progesterone levels when the mean values were
      plotted for all animal groups. Fpassive was unaffected by any treatment.
      CONCLUSION: Stress increases ovary-independent synthesis and release of
      progesterone, which may regulate Ca(2+)-sensitivity of force production in left
      ventricular cardiomyocytes. Stress and female hormones differently alter Ca(2+)
      dependent cardiomyocyte contractile force production, which may have
      pathophysiological importance during stress conditions affecting postmenopausal
      women.

PMID- 24891285
TI  - Less invasive treatment option for renal carcinoma with venous tumor thrombus.
AB  - AIM: To retrospectively analyze patients treated by renal tumor and venous tumor
      thrombus (VVT) removal and to introduce a less stressful and safer surgical
      method without thoracotomy in Neves level 3 cases. METHODS: From 2002 to 2011, 33
      patients underwent surgery for renal cell cancer combined with tumor thrombus of
      the inferior vena cava. Preoperative symptoms, tumor-node-metastasis
      classification of tumors, thrombus extension classified by Neves and Zincke
      system, types of surgical interventions, complications, postoperative management,
      and survival results were analyzed. RESULTS: Ten patients had level 1, 17 had
      level 2, and 6 had level 3 thrombi according to Neves and Zincke. In 5 patients
      with level 3 thrombi, the liver was mobilized without thoracotomy and in 1
      patient endoluminal occlusion was utilized. There was no intraoperative
      mortality. The median survival time of 10 patients who died during follow-up
      period was 36.6 months (range, 0-121 months). CONCLUSION: Renal cell cancer
      complicated with tumor thrombus without metastasis can be curable by performing a
      complete resection. The thrombus level determines the surgical approach and
      method. Our results confirm that level 3 caval vein tumor thrombus can be safely
      surgically treated by laparotomy with liver mobilization. Thoracotomy, use of
      cardiopulmonal bypass, and hypothermic circulatory arrest can be avoided with
      adequate liver- and vascular surgery methods.

PMID- 24891284
TI  - Detection of novel auto-antigens in patients with recurrent miscarriage:
      description of an approach and preliminary findings.
AB  - AIM: To develop and test a protocol for isolation of potential auto-antigens from
      chorionic tissue that may be linked to recurrent miscarriage (RM). METHODS: The
      strategy included: 1) isolation of IgGs tightly bound to chorionic tissue of RM
      patients by protein G chromatography; 2) construction of affinity columns using
      the chorionic antibodies for isolation of auto-antigens; 3) enrichment of auto
      antigens from detergent extracted solution of chorionic proteins by affinity
      chromatography; 4) separation by dodecyl sulfate-electrophoresis followed by
      matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      identification. RESULTS: Five potential auto-antigens were detected: neutral
      alpha-glucosidase AB, endoplasmin, transitional endoplasmic reticulum ATPase,
      putative endoplasmin-like protein, and cytoplasmic actin 2. CONCLUSIONS: We
      developed a strategy for identification of auto-antigens in the chorionic tissue
      of women with RM, which could be of diagnostic and prognostic value.

PMID- 24891286
TI  - Upgrading instructions for authors of scholarly journals.

PMID- 24891287
TI  - Marijuana use: neuroscience perspective.

PMID- 24891288
TI  - Author's response to the letter by Dr. Arjmand and Aghayan.

PMID- 24891289
TI  - Treg cell function in rheumatoid arthritis is compromised by ctla-4 promoter
      methylation resulting in a failure to activate the indoleamine 2,3-dioxygenase
      pathway.
AB  - OBJECTIVE: Functionally impaired Treg cells expressing abnormally low levels of
      CTLA-4 have been well documented in rheumatoid arthritis (RA). However, the
      molecular defect underlying this reduced expression is unknown. The aims of this
      study were to assess the role of DNA methylation in regulating CTLA-4 expression
      in Treg cells isolated from RA patients and to elucidate the mechanism of their
      reduced suppressor function. METHODS: CTLA-4 expression in Treg cells from RA
      patients and healthy controls was measured by quantitative polymerase chain
      reaction (PCR) and flow cytometry. Methylation of the CTLA-4 gene promoter was
      analyzed by bisulfite-specific PCR, followed by sequencing. Methylation-dependent
      transcriptional activity of the CTLA-4 gene promoter was measured by luciferase
      assay, and NF-AT binding to the CTLA-4 gene promoter was determined by chromatin
      immunoprecipitation. The role of CTLA-4 expression in controlling Teff cells was
      analyzed using an autologous mixed lymphocyte reaction. RESULTS: Down-regulation
      of CTLA-4 expression in Treg cells from RA patients was caused by methylation of
      a previously unidentified NF-AT binding site within the CTLA-4 gene promoter. As
      a consequence, Treg cells were unable to induce expression and activation of the
      tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO), which in turn
      resulted in a failure to activate the immunomodulatory kynurenine pathway.
      CONCLUSION: We show for the first time that epigenetic modifications contribute
      to defective Treg cell function in RA through an inability to activate the IDO
      pathway. Therefore, this study sets a precedent for investigating potential
      therapeutic strategies aimed at reinforcing the IDO pathway in RA patients.

PMID- 24891290
TI  - Detection and functionality of the CdtB, PltA, and PltB from Salmonella enterica
      serovar Javiana.
AB  - Salmonella infection is one of the major foodborne illnesses in the United
      States. Several Gram-negative bacterial pathogens, including Salmonella Typhi,
      produce cytolethal distending toxin (CDT), which arrests growth, induces
      apoptosis of infected host cells and extends persistence of pathogenic bacteria
      in the host. The aim of this study was to characterize the functionality of CDT
      (cdtB, pltA and pltB) from nontyphoidal Salmonella isolates. Fifty Salmonella
      enterica serovar Javiana isolates from food, environmental, and clinical samples
      were screened for cdtB, pltA, and pltB genes by PCR, and all were positive for
      all three genes. Nucleotide sequence analysis of all amplified PCR products
      showed 100% identity to S. Typhi cdtB. To understand the roles of CdtB, PltA, and
      PltB in S. Javiana, cdtB, pltA, and pltB deletion mutants were constructed using
      a lambda Red-based recombination system. In vitro-cultured HeLa cell lines were
      infected with a wild-type strain and its isogenic ?cdtB, ?pltA, and ?pltB to
      determine whether the strains of S. Javiana are responsible for invasion and
      cytolethal distending intoxication, including cell cycle arrest, cytoplasmic
      distension, and nuclear enlargement of host target cells. The results showed that
      HeLa cells infected with S. Javiana wild type were arrested in G2 /M and had
      distended cytoplasm and nuclei that were larger than those infected with S.
      Javiana ?cdtB and ?pltA strains. The S. Javiana ?pltB strain retained the ability
      to induce cytoplasmic distension and cell cycle arrest, whereas the complemented
      ?cdtB and ?pltA S. Javiana strains showed activity like the wild-type strains.
      CdtB and pltA from S. Javiana had apparent effects on the distension of both
      cytoplasm and nucleus as well as cell cycle arrest of HeLa cell lines after 72 h
      of infection. Our data show a significant difference between the wild-type cdtB
      strain and its isogenic ?cdtB for invasion of the cell lines. Therefore, CdtB
      produced from S. Javiana strains may play an important role in pathogenesis in
      host cells.

PMID- 24891291
TI  - Effect of nanosecond pulsed electric field on Escherichia coli in water:
      inactivation and impact on protein changes.
AB  - AIMS: This article shows the effect of nanosecond pulsed electric field (nsPEF)
      on Escherichia coli, which could imply a durable change in protein expressions
      and then impacted the phenotype of surviving bacteria that might lead to increase
      pathogenicity. METHODS AND RESULTS: The effects of nsPEF on E. coli viability and
      membrane permeabilization were investigated. One log10 reduction in bacterial
      counts was achieved at field strength of 10(7) V m(-1) with a train of 500
      successive pulses of 60 * 10(-9) s. Incubation of germs after treatment with
      propidium iodide showed that membrane permeabilization was reversible. Possible
      protein changes of surviving bacteria were checked to assess potential
      phenotypical changes using two-dimensional electrophoresis. In our study, after
      40 generations, only UniProt #P39187 was up-regulated with P <= 0.05 compared
      with the control and corresponded to the uncharacterized protein YtfJ.
      Antibiograms were used to check whether or not the pattern of cultivable bacteria
      after nsPEF deliveries changed. CONCLUSIONS: The results tend to show that nsPEFs
      are able to inactivate bacteria and have probably no serious impact in E. coli
      protein patterns. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of nsPEF is a
      safe promising new nonthermal method for bacterial inactivation in the food
      processing and environmental industry.

PMID- 24891293
TI  - Challenges of studying viral aerosol metagenomics and communities in comparison
      with bacterial and fungal aerosols.
AB  - Despite the obvious importance of viral transmission and ecology to medicine,
      epidemiology, ecology, agriculture, and microbiology, the study of viral
      bioaerosols and community structure has remained a vastly underexplored area, due
      to both unresolved technical challenges and unrecognized importance. High
      throughput, culture-independent techniques such as viral metagenomics are
      beginning to revolutionize the study of viral ecology. With recent developments
      in viral metagenomics, characterization of viral bioaerosol communities provides
      an opportunity for high-impact future research. However, there remain significant
      challenges for the study of viral bioaerosols compared with viruses in other
      matrices, such as water, the human gut, and soil. Collecting enough biomass is
      essential for successful metagenomic analysis, but this is a challenge with viral
      bioaerosols. Herein, we provide a perspective on the importance of studying viral
      bioaerosols, the challenges of studying viral community structure, and the
      potential opportunities for improvements in methods to study viruses in indoor
      and outdoor air.

PMID- 24891294
TI  - Reflections on sampling, extrapolation and interpretation.

PMID- 24891292
TI  - Differential contributions of intra-cellular and inter-cellular mechanisms to the
      spatial and temporal architecture of the suprachiasmatic nucleus circadian
      circuitry in wild-type, cryptochrome-null and vasoactive intestinal peptide
      receptor 2-null mutant mice.
AB  - To serve as a robust internal circadian clock, the cell-autonomous molecular and
      electrophysiological activities of the individual neurons of the mammalian
      suprachiasmatic nucleus (SCN) are coordinated in time and neuroanatomical space.
      Although the contributions of the chemical and electrical interconnections
      between neurons are essential to this circuit-level orchestration, the features
      upon which they operate to confer robustness to the ensemble signal are not
      known. To address this, we applied several methods to deconstruct the
      interactions between the spatial and temporal organisation of circadian
      oscillations in organotypic slices from mice with circadian abnormalities. We
      studied the SCN of mice lacking Cryptochrome genes (Cry1 and Cry2), which are
      essential for cell-autonomous oscillation, and the SCN of mice lacking the
      vasoactive intestinal peptide receptor 2 (VPAC2-null), which is necessary for
      circuit-level integration, in order to map biological mechanisms to the revealed
      oscillatory features. The SCN of wild-type mice showed a strong link between the
      temporal rhythm of the bioluminescence profiles of PER2::LUC and regularly
      repeated spatially organised oscillation. The Cry-null SCN had stable spatial
      organisation but lacked temporal organisation, whereas in VPAC2-null SCN some
      specimens exhibited temporal organisation in the absence of spatial organisation.
      The results indicated that spatial and temporal organisation were separable, that
      they may have different mechanistic origins (cell-autonomous vs. interneuronal
      signaling) and that both were necessary to maintain robust and organised
      circadian rhythms throughout the SCN. This study therefore provided evidence that
      the coherent emergent properties of the neuronal circuitry, revealed in the
      spatially organised clusters, were essential to the pacemaking function of the
      SCN. 

PMID- 24891295
TI  - CD30-positive lymphoproliferative disorders arising after regional therapy for
      recurrent melanoma: a report of two cases and analysis of CD30 expression.
AB  - BACKGROUND AND OBJECTIVES: Primary cutaneous CD30-positive T-cell
      lymphoproliferative disorders (CD30(+) LPD), including primary cutaneous
      anaplastic large cell lymphoma (CALCL) and lymphomatoid papulosis (LyP), comprise
      the second most common group of cutaneous T-cell lymphomas (CTCL). The etiology
      of these disorders is not known. Isolated limb perfusion (ILP) and isolated limb
      infusion (ILI) are forms of regional chemotherapy used to treat recurrent tumors
      of the extremity, most commonly, melanoma. Secondary malignancy following
      regional therapy is rarely reported. METHODS/RESULTS: We identified two cases of
      CD30(+) LPD arising in the affected limbs of patients treated with ILP/ILI. We
      subsequently performed CD30 immunohistochemical stains on 11 pre- and post
      treatment skin specimens from melanoma patients treated with ILP/ILI and found
      that 5 of the 11 cases showed an increase in CD30(+) lymphocytes following
      ILP/ILI. CONCLUSIONS: We hypothesize that ILP/ILI causes upregulation of CD30
      expression in the extremities of treated patients, and suggest that this may be a
      marker of treatment response. However, a rare but long-term effect may be an
      increased risk of T-cell cutaneous lymphoproliferative disease in the affected
      limb.

PMID- 24891296
TI  - A PTPN11 allele encoding a catalytically impaired SHP2 protein in a patient with
      a Noonan syndrome phenotype.
AB  - The RASopathies are a relatively common group of phenotypically similar and
      genetically related autosomal dominant genetic syndromes caused by missense
      mutations affecting genes participating in the RAS/mitogen-activated protein
      kinase (MAPK) pathway that include Noonan syndrome (NS) and Noonan syndrome with
      multiple lentigines (NSML, formerly LEOPARD syndrome). NS and NSML can be
      difficult to differentiate during infancy, but the presence of multiple
      lentigines, cafe au lait spots, and specific cardiac defects facilitate the
      diagnosis. Furthermore, individual PTPN11 missense mutations are highly specific
      to each syndrome and engender opposite biochemical alterations on the function of
      SHP-2, the protein product of that gene. Here, we report on a 5-year-old male
      with two de novo PTPN11 mutations in cis, c.1471C>T (p.Pro491Ser), and c.1492C>T
      (p.Arg498Trp), which are associated with NS and NSML, respectively. This boy's
      phenotype is intermediate between NS and NSML with facial dysmorphism, short
      stature, mild global developmental delay, pulmonic stenosis, and deafness but
      absence of cafe au lait spots or lentigines. The double-mutant SHP-2 was found to
      be catalytically impaired. This raises the question of whether clinical
      differences between NS and NSML can be ascribed solely to the relative SHP-2
      catalytic activity.

PMID- 24891297
TI  - Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol
      protects against post-infarct heart failure in mouse hearts.
AB  - AIMS: Recently it has been shown that the mitochondria-targeted S-nitrosothiol
      MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting
      the reactivation of mitochondrial complex I in the first minutes of reperfusion
      of ischaemic tissue, thereby preventing free radical formation that underlies IR
      injury. However, it remains unclear how this transient inhibition of
      mitochondrial complex I-mediated free radicals at reperfusion affects the long
      term recovery of the heart following IR injury. Here we determined whether the
      acute protection by MitoSNO at reperfusion prevented the subsequent development
      of post-myocardial infarction heart failure. METHODS AND RESULTS: Mice were
      subjected to 30 min left coronary artery occlusion followed by reperfusion and
      recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of
      reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac
      function were measured by magnetic resonance imaging (MRI) 24 h after infarction.
      MitoSNO-treated mice exhibited reduced infarct size and preserved function. In
      addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR,
      including preserved systolic function (63.7 +/-1.8% LVEF vs. 53.7 +/- 2.1% in
      controls, P = 0.01) and tissue fibrosis. CONCLUSIONS: MitoSNO action acutely at
      reperfusion reduces infarct size and protects from post-myocardial infarction
      heart failure. Therefore, targeted inhibition of mitochondrial complex I in the
      first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for
      preventing subsequent heart failure in patients undergoing IR injury.

PMID- 24891299
TI  - The best years.

PMID- 24891298
TI  - microRNA-mediated survivin control of pluripotency.
AB  - Understanding the mechanisms that sustain pluripotency in human embryonic stem
      cells (hESCs) is an active area of research that may prove useful in regenerative
      medicine and will provide fundamental information relevant to development and
      cancer. hESCs and cancer cells share the unique ability to proliferate
      indefinitely and rapidly. Because the protein survivin is uniquely overexpressed
      in virtually all human cancers and in hESCs, we sought to investigate its role in
      supporting the distinctive capabilities of these cell types. Results presented
      here suggest that survivin contributes to the maintenance of pluripotency and
      that post-transcriptional control of survivin isoform expression is selectively
      regulated by microRNAs. miR-203 has been extensively studied in human tumors, but
      has not been characterized in hESCs. We show that miR-203 expression and activity
      is consistent with the expression and subcellular localization of survivin
      isoforms that in turn modulate expression of the Oct4 and Nanog transcription
      factors to sustain pluripotency. This study contributes to understanding of the
      complex regulatory mechanisms that govern whether hESCs proliferate or commit to
      lineages.

PMID- 24891300
TI  - Norcantharidin enhances ABT-263-mediated anticancer activity in neuroblastoma
      cells by upregulation of Noxa.
AB  - Neuroblastoma is an aggressive childhood disease. Even with intensive
      conventional treatments, the long term survival rate for children with
      neuroblastoma remains less than 40%, highlighting the importance of finding new
      therapies. Bcl-2 family proteins play crucial roles in survival, proliferation
      and chemotherapeutic resistance of neuroblastoma cells. Therefore, targeting Bcl
      2 with small molecule inhibitor ABT-263 could be a novel strategy for treatment
      of neuroblastoma. However, previous studies indicated that most neuroblastoma
      cell lines are resistant to ABT-263-mediated apoptosis. Thus, it is crucial to
      discover approaches that could overcome ABT-263 resistance. In this study, we
      examined the anticancer activity of ABT-263 in combination with norcantharidin
      (NCTD), a small-molecule anticancer drug derived from a traditional Chinese
      medicine, in human malignant neuroblastoma cells. We found that NCTD
      substantially enhanced ABT-263-mediated apoptosis induction, cell viability
      inhibition, and clonal formation inhibition in neuroblastoma SH-SY5Y and CHLA-119
      cell lines. Moreover, the combination anticancer activity was accompanied by
      upregulation of Noxa, and was associated with characteristics of mitochondrial
      apoptosis signaling, such as cytosolic release of cytochrome c, activation of
      caspase-9,-3, and cleavage of PARP. Notably, we observed that knockdown of Noxa
      significantly attenuated cell death induction by cotreatment with ABT-263 and
      NCTD, indicating Noxa essentially contributes to the combination anticancer
      effect. Collectively, our study demonstrated that NCTD could overcome ABT-263
      resistance in neuroblastoma cells, and suggested that combinational treatment of
      ABT-263 with NCTD might be a novel therapeutic option for children with
      neuroblastoma.

PMID- 24891302
TI  - Author's reply: To PMID 24262817.

PMID- 24891301
TI  - Interleukin-6 deficiency corrects nephritis, lymphocyte abnormalities, and
      secondary Sjogren's syndrome features in lupus-prone Sle1.Yaa mice.
AB  - OBJECTIVE: To assess disease features in Sle1.Yaa mice with genetic interleukin-6
      (IL-6) deficiency. METHODS: Sera and tissues were collected from C57BL/6 (B6),
      Sle1.Yaa, and Sle1.Yaa.IL-6(-/-) mice and analyzed for various features of
      disease. Using serum samples, autoantibody specificities were determined by
      enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence,
      cytokine production was analyzed by Luminex and ELISA, and levels of blood urea
      nitrogen were determined by ELISA. Renal, lung, and salivary gland tissue
      sections were evaluated for pathologic changes. Lymphocyte phenotypes, including
      CD4+ T cell cytokine production, and those of follicular and extrafollicular T
      helper subsets, germinal center B cells, and plasma cells, were determined using
      flow cytometry. RESULTS: IL-6 deficiency not only ameliorated autoantibody
      production and renal disease in this model, but also effectively reduced
      inflammation of lungs and salivary glands. Furthermore, IL-6 deficiency abrogated
      differentiation of Th1 and extrafollicular T helper cells, germinal center B
      cells, and plasma cells in the spleen and eliminated renal T cells with IL-17,
      interferon-gamma, and IL-21 production potential. CONCLUSION: Our findings
      highlight IL-6-mediated T cell aberrations in Yaa-driven autoimmunity and support
      the concept of therapeutic IL-6/IL-6 receptor blockade in systemic lupus
      erythematosus and Sjogren's syndrome by impairing the production of
      autoantibodies and lymphocytic infiltration of the kidneys, lungs, and salivary
      glands.

PMID- 24891304
TI  - "Stiffness has different meanings, I think, to everyone": examining stiffness
      from the perspective of people living with rheumatoid arthritis.
AB  - OBJECTIVE: Stiffness is a well-recognized symptom of rheumatoid arthritis (RA).
      It is frequently queried during clinic visits as an indicator of disease activity
      and was included in the 1961 and 1987 RA classification criteria. Little is known
      about how people with RA experience stiffness and its impact on their lives.
      METHODS: We conducted 4 focus groups including 20 people with RA (4-6
      participants per group) from 1 academic clinical practice and 1 private practice
      to generate accounts of stiffness experiences. Qualitative inductive thematic
      data analysis was conducted. RESULTS: Five overarching themes were identified:
      relationship of stiffness with other symptoms, exacerbating or alleviating
      factors and self-management, stiffness timing and location, individual meanings
      of stiffness experiences, and impact of stiffness on daily life. CONCLUSION:
      Focus group discussions revealed individual stiffness experiences as diverse and
      complex. Several stiffness features were endorsed by a majority of participants,
      but few, if any, were universally experienced; thus, the significance of
      stiffness as an expression of the disease varied widely. Discussions yielded
      descriptions of how individual limits imposed by RA in general and stiffness in
      particular may change over time and were intertwined with adaptations to preserve
      participation in valued life activities. These results concerning the diversity
      of the stiffness experience, consequential adaptations, and its impact suggest
      that a more individualized approach to stiffness measurement may be needed to
      improve stiffness assessments.

PMID- 24891305
TI  - Transhiatal versus transthoracic esophagectomy for esophageal cancer: a 2005-2011
      NSQIP comparison of modern multicenter results.
AB  - BACKGROUND: The surgical approach to esophageal cancer continues to be
      controversial. A transthoracic approach is often advocated for better oncologic
      staging and improved survival. A transhiatal approach is often preferred due to a
      perceived decreased operative morbidity and mortality. METHODS: Using the
      American College of Surgeons-National Surgical Quality Improvement Project (ACS
      NSQIP) participant-use file, patients were identified who underwent either a
      transhiatal or transthoracic esophagectomy for cancer at participating hospitals
      from 2005 to 2011. Demographic, clinical, intra-operative variables, and 30-day
      morbidity and mortality were collected. RESULTS: Of the 1,428 patients that had
      esophagectomy, 750 (52.5%) had a transhiatal (TH) resection and 678 (47.5%) had a
      transthoracic (TT) resection. The transhiatal group was older (66 vs. 63 years, P
      = 0.003) with a lower ASA class (2.84 vs. 2.91, P = 0.025). Operative time was
      greater in the TT group (364 vs. 298 min, P < 0.001). There was no significant
      difference in 30 day overall mortality (TH = 2.9%, TT = 4.7%, P = 0.095) however
      a trend favored the TH group. Serious morbidity remains clinically significant in
      both groups (TH = 39.6%, TT = 43.5%, P = 0.146). The TH group had a significantly
      higher superficial wound infection rate (11.6% vs. 6.2%, P < 0.001) while the TT
      group required more perioperative blood transfusions (12.5% vs. 8.9%, P = 0.032)
      and returns to operating room (14.5% vs. 10.9%, P = 0.046). CONCLUSION: Serious
      morbidity continues to be high for both types of esophagectomy. There needs to be
      continued efforts to diminish these complications.

PMID- 24891311
TI  - Recovery from chemotherapy depends on STAT1 for replenishment of B lymphopoiesis.

PMID- 24891310
TI  - Reply: To PMID 24504799.

PMID- 24891312
TI  - Does tocilizumab indeed reduce the frequency of Th17 cells? Comment on the
      article by Thiolat et al.

PMID- 24891313
TI  - Focus on rice: towards better understanding of the life cycle of crop plants.

PMID- 24891314
TI  - Insights into the significance of peptidylarginine deiminase 4 and antibodies
      against citrullinated antigens in the absence of "true ACPAs" in an experimental
      model of arthritis: comment on the article by Shelef et al.

PMID- 24891315
TI  - Prevalence and incidence of systemic lupus erythematosus in a population-based
      registry of American Indian and Alaska Native people, 2007-2009.
AB  - OBJECTIVE: Few studies have investigated the epidemiology of systemic lupus
      erythematosus (SLE) in American Indian and Alaska Native populations. The
      objective of this study was to determine the prevalence and incidence of SLE in
      the Indian Health Service (IHS) active clinical population in 3 regions of the
      US. METHODS: For this population-based registry within the IHS, the denominator
      consisted of individuals in the IHS active clinical population in 2007, 2008,
      and/or 2009 and residing in a community in 1 of 3 specified regions. Potential
      SLE cases were identified based on the presence of a diagnostic code for SLE or
      related disorder in the IHS National Data Warehouse. Detailed medical record
      abstraction was performed for each potential case. The primary case definition
      was documentation in the medical record of >=4 of the revised American College of
      Rheumatology criteria for the classification of SLE. Prevalence was calculated
      for 2007, and the mean annual incidence was calculated for the years 2007 through
      2009. RESULTS: The age-adjusted prevalence and incidence of SLE according to the
      primary definition were 178 per 100,000 person-years (95% confidence interval
      [95% CI] 157-200) and 7.4 per 100,000 person-years (95% CI 5.1-10.4). Among
      women, the age-adjusted prevalence was 271, and the age-adjusted incidence was
      10.4. The prevalence was highest in women ages 50-59 years and in the Phoenix
      Area IHS. CONCLUSION: The first population-based lupus registry in the US
      American Indian and Alaska Native population has demonstrated that the prevalence
      and incidence of SLE are high. Our estimates are as high as or higher than the
      rates reported in the US black population.

PMID- 24891316
TI  - Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic
      obstructive pulmonary disease and lung cancer development in Chinese population.
AB  - Lung inflammation and epithelial to mesenchymal transition (EMT) are two
      pathogenic features for the two contextual diseases: chronic obstructive
      pulmonary disease (COPD) and lung cancer. VEGFR1 (or FLT1) plays a certain role
      in promoting tumour growth, inflammation and EMT. To simultaneously test the
      association between the single nucleotide polymorphisms (SNPs) in VEGFR1 and risk
      of COPD and lung cancer would reveal genetic mechanisms shared by these two
      diseases and joint aetiology. We conducted a two-population hospital-based case
      control study. Three potential functional SNPs (rs664393, rs7326277 and
      rs9554314) were genotyped in southern Chinese and validated in eastern Chinese to
      explore their associations with COPD risk in 1511 COPD patients and 1677 normal
      lung function controls, and with lung cancer risk in 1559 lung cancer cases and
      1679 cancer-free controls. We also detected the function of the promising SNP.
      Individuals carrying the rs7326277C (CT+CC) variant genotypes of VEGFR1 had a
      significant decrease in risk of both COPD (OR = 0.78; 95% CI = 0.68-0.90) and
      lung cancer (OR = 0.79; 95% CI = 0.64-0.98), compared with those carrying the
      rs7326277TT genotype. Functional assays further showed that the rs7326277C
      genotypes had lower transcriptional activity and caused decreased VEGFR
      expression, compared with the rs7326277TT genotype. However, no significant
      association was observed for the other two SNPs (rs664393 and rs9554314) and
      either COPD or lung cancer risk. Our data suggested that the rs7326277C variant
      of VEGFR1 could reduce both COPD and lung cancer risk by lowering VEGFR1 mRNA
      expression; the SNP might be a common susceptible locus for both COPD and lung
      cancer. 

PMID- 24891318
TI  - Reply: To PMID 24497204.

PMID- 24891317
TI  - Symptomatic efficacy of etanercept and its effects on objective signs of
      inflammation in early nonradiographic axial spondyloarthritis: a multicenter,
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To assess the efficacy of etanercept in the treatment of early active
      nonsteroidal antiinflammatory drug (NSAID)-refractory nonradiographic axial
      spondyloarthritis (SpA). METHODS: The study population consisted of patients who
      met the Assessment of SpondyloArthritis international Society (ASAS)
      classification criteria for axial SpA but not the modified New York radiographic
      criteria for ankylosing spondylitis (as assessed by a radiologist at the central
      trial site), had a symptom duration of >3 months but <5 years, had a score of >=4
      on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated
      unsuccessfully with >=2 NSAIDs. Patients were randomized to receive etanercept 50
      mg/week or placebo and continued background NSAID treatment for 12 weeks (double
      blind study); during the subsequent open-label period, all patients received
      etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria
      for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the
      sacroiliac joints and spine was performed at baseline and week 12. RESULTS: One
      hundred six patients were randomized to the etanercept group and 109 to the
      placebo group. Of the 215 patients, the mean +/- SD age at baseline was 32.0 +/-
      7.8 years, 154 (72%) were HLA-B27 positive, and 174 (81%) had MRI-confirmed
      sacroiliitis. At 12 weeks, the proportion of patients with improvement according
      to the ASAS40 was significantly higher in the etanercept group than in the
      placebo group (34 of 105 [32%] versus 17 of 108 [16%]; P = 0.006). Patients who
      received etanercept exhibited a greater reduction in MRI-based scores for
      sacroiliac joint inflammation (-46.9% versus -10.9%; P < 0.001) and spinal
      inflammation (-45.4% versus -33.4%; P = 0.04) compared with placebo-treated
      patients at week 12. Post hoc analyses suggested a possible association between
      higher baseline C-reactive protein levels or MRI sacroiliac joint inflammation
      scores and higher rates of ASAS40 response to etanercept. At week 24, patients in
      the placebo group who had switched to etanercept at 12 weeks exhibited
      improvement similar to that observed in patients who had received etanercept for
      24 weeks. CONCLUSION: In patients with nonradiographic axial SpA, etanercept
      treatment was associated with rapid, significant improvement in symptomatic
      disease activity, function, and systemic and skeletal inflammation over 12 weeks;
      clinical/functional improvement was sustained over 24 weeks.

PMID- 24891319
TI  - Macrophage migration inhibitory factor down-regulates the RANKL-RANK signaling
      pathway by activating Lyn tyrosine kinase in mouse models.
AB  - OBJECTIVE: Macrophage migration inhibitory factor (MIF) is an important modulator
      of innate and adaptive immunity as well as local inflammatory responses. We
      previously reported that MIF down-regulated osteoclastogenesis through a
      mechanism that requires CD74. The aim of the current study was to examine whether
      MIF modulates osteoclastogenesis through Lyn phosphorylation, and whether down
      regulation of RANKL-mediated signaling requires the association of CD74, CD44,
      and Lyn. METHODS: CD74-knockout (CD74-KO), CD44-KO, and Lyn-KO mouse models were
      used to investigate whether Lyn requires these receptors and coreceptors. The
      effects of MIF on osteoclastogenesis were assessed using Western blot analysis,
      small interfering RNA (siRNA)-targeted down-regulation of Lyn, Lyn-KO mice, and
      real-time imaging of Lyn molecules to surface proteins. RESULTS: MIF treatment
      induced Lyn expression, and MIF down-regulated RANKL-induced activator protein 1
      (AP-1) and the Syk/phospholipase Cgamma cascade during osteoclastogenesis through
      activated Lyn tyrosine kinase. The results of immunoprecipitation studies
      revealed that MIF receptors associated with Lyn in response to MIF treatment.
      Studies using Lyn-specific siRNA and Lyn-KO mice confirmed our findings.
      CONCLUSION: Our findings indicate that the tyrosine kinase Lyn is activated when
      MIF binds to its receptor CD74 and its coreceptor CD44 and, in turn, down
      regulates the RANKL-mediated signaling cascade by suppressing NF-ATc1 protein
      expression through down-regulation of AP-1 and calcium signaling components.

PMID- 24891320
TI  - Transcription of the activating receptor NKG2D in natural killer cells is
      regulated by STAT3 tyrosine phosphorylation.
AB  - Signal transducer and activator of transcription 3 (STAT3) is considered a
      negative regulator of inflammation, as inhibition of STAT3 signaling enhances
      antitumor immunity. However, STAT3 activation is a key oncogenic pathway in
      natural killer (NK)-lineage large granular lymphomas, and we recently reported
      enhanced proliferation and function of human NK cells activated with IL-21, which
      signals primarily through STAT3. These IL-21-expanded NK cells also have
      increased NKG2D expression, which led us to focus our investigation on whether
      STAT3 regulates NKG2D. In this study, we show that modulation of STAT3
      phosphorylation with cytokines and small-molecule inhibitors correlates with
      NKG2D expression on human NK cells, leading to altered NK-cell degranulation.
      Moreover, NKG2D expression on murine NK cells having conditional STAT3 ablation
      is lower than on NK cells from wild-type mice, and human NK cells carrying
      dominant-negative STAT3 mutations have decreased baseline NKG2D expression and
      blunted responses to IL-10 and IL-21. Lastly, we show binding of STAT3 to a
      predicted STAT3 binding site upstream of the NKG2D gene, which is enhanced by IL
      10 and IL-21 and decreased by STAT3 inhibition. Taken together, these data show
      that NKG2D expression in NK cells is regulated at the transcriptional level by
      STAT3, resulting in a functional NK cell defect in patients with STAT3 mutations.

PMID- 24891321
TI  - Systematic identification of personal tumor-specific neoantigens in chronic
      lymphocytic leukemia.
AB  - Genome sequencing has revealed a large number of shared and personal somatic
      mutations across human cancers. In principle, any genetic alteration affecting a
      protein-coding region has the potential to generate mutated peptides that are
      presented by surface HLA class I proteins that might be recognized by cytotoxic T
      cells. To test this possibility, we implemented a streamlined approach for the
      prediction and validation of such neoantigens derived from individual tumors and
      presented by patient-specific HLA alleles. We applied our computational pipeline
      to 91 chronic lymphocytic leukemias (CLLs) that underwent whole-exome sequencing
      (WES). We predicted ~22 mutated HLA-binding peptides per leukemia (derived from
      ~16 missense mutations) and experimentally confirmed HLA binding for ~55% of such
      peptides. Two CLL patients that achieved long-term remission following allogeneic
      hematopoietic stem cell transplantation were monitored for CD8(+) T-cell
      responses against predicted or confirmed HLA-binding peptides. Long-lived
      cytotoxic T-cell responses were detected against peptides generated from personal
      tumor mutations in ALMS1, C6ORF89, and FNDC3B presented on tumor cells. Finally,
      we applied our computational pipeline to WES data (N = 2488 samples) across 13
      different cancer types and estimated dozens to thousands of predicted neoantigens
      per individual tumor, suggesting that neoantigens are frequent in most tumors. 

PMID- 24891323
TI  - B-cell prolymphocytic leukemia: a specific subgroup of mantle cell lymphoma.
AB  - B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell malignancy that
      may be hard to distinguish from mantle cell lymphoma (MCL) and chronic
      lymphocytic leukemia (CLL). B-PLL cases with a t(11;14) were redefined as MCL in
      the World Health Organization 2008 classification. We evaluated 13 B-PLL patients
      [7 being t(11;14)-positive (B-PLL+) and 6 negative (B-PLL-)] and compared them
      with MCL and CLL patients. EuroFlow-based immunophenotyping showed significant
      overlap between B-PLL+ and B-PLL-, as well as between B-PLL and MCL, whereas CLL
      clustered separately. Immunogenotyping showed specific IGHV gene usage partly
      resembling MCL. Gene expression profiling showed no separation between B-PLL+ and
      B-PLL- but identified 3 subgroups. One B-PLL subgroup clustered close to CLL and
      another subgroup clustered with leukemic MCL; both were associated with prolonged
      survival. A third subgroup clustered close to nodal MCL and was associated with
      short survival. Gene expression profiles of both B-PLL+ and B-PLL- showed best
      resemblance with normal immunoglobulin M-only B-cells. Our data confirm that B
      PLL+ is highly comparable to MCL, indicate that B-PLL- also may be considered as
      a specific subgroup of MCL, and suggest that B-PLL is part of a spectrum, ranging
      from CLL-like B-PLL, to leukemic MCL-like B-PLL, to nodal MCL-like B-PLL. 

PMID- 24891324
TI  - Contribution of transient receptor potential ankyrin 1 to chronic pain in aged
      mice with complete Freund's adjuvant-induced arthritis.
AB  - OBJECTIVE: To investigate age-related differences in mechanical sensitivity to
      inflammatory pain and determine the contribution of transient receptor potential
      ankyrin 1 (TRPA1) to mechanical hypersensitivity during chronic inflammation in
      young and aged mice with complete Freund's adjuvant (CFA)-induced arthritis.
      METHODS: Mechanical sensitivity in young (3-month-old) and aged (24-month-old)
      wild-type (TRPA1(+/+) ) mice and TRPA1-deficient (TRPA1(-/-) ) mice was measured
      behaviorally for 8 weeks following injection of CFA into the plantar hind paw.
      The severity of inflammation was evaluated by histologic analyses and hind-paw
      measurements. Ex vivo preparations of the skin saphenous nerve from mice were
      assessed for C-fiber sensitivity. RESULTS: Among naive (uninjured) wild-type
      mice, aged animals were less sensitive than young animals to mechanical stimuli.
      Afferent recordings of C-fibers from TRPA1(-/-) mice indicated that TRPA1
      contributes to the normal mechanical sensitivity in both age groups. Following
      injection of CFA, both young and aged TRPA1(+/+) mice exhibited mechanical
      hypersensitivity. In young TRPA1(-/-) mice injected with CFA, peak development of
      mechanical hypersensitivity was delayed until week 4, when they exhibited a sharp
      decrease (9-fold) in the mechanical paw withdrawal threshold, whereas aged TRPA1(
      /-) mice did not exhibit mechanical hypersensitivity at any time during the 8
      weeks after CFA injection. Recordings of C-fibers from the saphenous nerve
      supported these findings, with results indicating that both young and aged
      TRPA1(+/+) mice exhibited increased action potential firing at 8 weeks after CFA
      injection (increases of 25% and 60%, respectively). Interestingly, among TRPA1(-/
      ) mice injected with CFA, mechanical firing was increased markedly in the C
      fibers of young mice (increase of 80%) but not in the C-fibers of aged mice.
      CONCLUSION: These findings reveal marked differences in the long-term mechanical
      behavioral sensitivity of aged and young mice, and suggest that TRPA1 may be a
      key contributor to the transition from acute to chronic inflammatory pain in
      response to mechanical stimuli as well as to the development of nociceptor
      sensitization selectively in aged mice.

PMID- 24891322
TI  - Aberrant overexpression of CD14 on granulocytes sensitizes the innate immune
      response in mDia1 heterozygous del(5q) MDS.
AB  - The myelodysplastic syndromes (MDSs) include a spectrum of stem cell malignancies
      characterized by an increased risk of developing acute myeloid leukemia.
      Heterozygous loss of chromosome 5q (del[5q]) is the most common cytogenetic
      abnormality in MDS. DIAPH1 is localized to 5q31 and encodes one of the formin
      proteins, mDia1, which is involved in linear actin polymerization. Mice with
      mDia1 deficiency develop hematologic features with age mimicking human myeloid
      neoplasm, but its role in the pathogenesis of MDS is unclear. Here we report that
      mDia1 heterozygous and knockout mice develop MDS phenotypes with age. In these
      mice, CD14 was aberrantly overexpressed on granulocytes in a cell-autonomous
      manner, leading to a hypersensitive innate immune response to lipopolysaccharide
      (LPS) stimuli through CD14/Toll-like receptor 4 signaling. Chronic stimulation
      with LPS accelerated the development of MDS in mDia1 heterozygous and knockout
      mice that can be rescued by lenalidomide. Similar findings of CD14 overexpression
      were observed on the bone marrow granulocytes of del(5q) MDS patients.
      Mechanistically, mDia1 deficiency led to a downregulation of membrane-associated
      genes and a specific upregulation of CD14 messenger RNA in granulocytes, but not
      in other lineages. These results underscore the significance of mDia1
      heterozygosity in deregulated innate immune responses in del(5q) MDS. 

PMID- 24891326
TI  - A longitudinal study of lung function from 1 month to 18 years of age.
AB  - BACKGROUND: Our hypothesis was that factors associated with wheeze will be
      associated with changes in lung function trajectory between 1 month and 18 years
      of age. METHODS: Measurements of lung function were made in individuals aged 1, 6
      and 12 months (V'maxFRC), and also at ages 6, 12 and 18 years (FEF(25-75)).
      Changes in lung function over time relative to sex, a history of asthma, maternal
      asthma and other factors were explored using random coefficient models. RESULTS:
      Lung function (maximal flow at functional residual capacity in infants and FEF(25
      75) in children) was determined in 241 individuals at 1 month, 192 at 6 months,
      164 at 12 months, 106 at 6 years, 183 at 12 years and 141 at 18 years. In the
      multivariable model, maternal asthma (mean reduction in lung function 9.8%), flow
      limitation (mean reduction 17.4%), infant atopy (mean reduction 12.6%) and
      maternal smoking (mean reduction in lung function 8.1%) were acting
      independently. When interactions with time were sought, the reduction in lung
      function associated with maternal asthma and infant atopy were consistent over
      time, but % lung function increased in boys by a mean of 1%/year compared with
      girls, in flow-limited individuals by 3.0%/year and by 0.9%/year for those
      exposed to maternal smoking during pregnancy compared to other cohort members.
      CONCLUSIONS: Decrements in lung function in 18-year-olds associated with maternal
      asthma and early onset atopy may be determined by 1 month of age. Low initial
      lung function in some individuals can 'recover' in some settings.

PMID- 24891325
TI  - Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep
      model of bacterial pneumonia.
AB  - BACKGROUND: Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs)
      improve survival in mouse models of acute respiratory distress syndrome (ARDS)
      and reduce pulmonary oedema in a perfused human lung preparation injured with
      Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce
      the severity of acute lung injury (ALI) and would be safe in a sheep model of
      ARDS. METHODS: Adult sheep (30-40 kg) were surgically prepared. After 5 days of
      recovery, ALI was induced with cotton smoke insufflation, followed by
      instillation of live Pseudomonas aeruginosa (2.5*10(11) CFU) into both lungs
      under isoflurane anaesthesia. Following the injury, sheep were ventilated,
      resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were
      randomly allocated to receive one of the following treatments intravenously over
      1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower
      dose hMSCs, 5*10(6) hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10*10(6) hMSCs/kg,
      n=4. RESULTS: By 24 h, the PaO2/FiO2 ratio was significantly improved in both
      hMSC treatment groups compared with the control group (control group: PaO2/FiO2
      of 97+/-15 mm Hg; lower dose: 288+/-55 mm Hg (p=0.003); higher dose: 327+/-2 mm
      Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC
      treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR
      4.9-5.8] vs control: 6.7 g wet/g dry [IQR 6.4-7.5] (p=0.01)). The hMSCs had no
      adverse effects. CONCLUSIONS: Human MSCs were well tolerated and improved
      oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS. TRAIL
      REGISTRATION NUMBER: NCT01775774 for Phase 1. NCT02097641 for Phase 2.

PMID- 24891328
TI  - Editorial: What caused all these troubles, anyway? Epstein-Barr virus in
      Sjogren's syndrome reevaluated.

PMID- 24891327
TI  - Lung volume reduction coil treatment for patients with severe emphysema: a
      European multicentre trial.
AB  - BACKGROUND: The lung volume reduction (LVR) coil is a minimally invasive
      bronchoscopic nitinol device designed to reduce hyperinflation and improve
      elastic recoil in severe emphysema. We investigated the feasibility, safety and
      efficacy of LVR coil treatment in a prospective multicentre cohort trial in
      patients with severe emphysema. METHODS: Patients were treated in 11 centres.
      Safety was evaluated by recording all adverse events, efficacy by the St George's
      Respiratory Questionnaire (SGRQ) as primary endpoint, and pulmonary function
      testing, modified Medical Research Council dyspnoea score (mMRC) and 6-min walk
      distance (6MWD) up to 12 months after the final treatment. RESULTS: Sixty
      patients (60.9 +/- 7.5 years, forced expiratory volume in 1 s (FEV(1)) 30.2 +/-
      6.3% pred) were bronchoscopically treated with coils (55 bilateral, 5
      unilateral), with a median of 10 (range 5-15) coils per lobe. Within 30 days post
      treatment, seven chronic obstructive pulmonary disease exacerbations (6.1%), six
      pneumonias (5.2%), four pneumothoraces (3.5%) and one haemoptysis (0.9%) occurred
      as serious adverse events. At 6 and 12 months, respectively, DeltaSGRQ was 
      12.1+/-12.9 and -11.1+/-13.3 points, Delta6MWD was +29.7+/-74.1 m and +51.4+/-76
      m, DeltaFEV(1) was +0.11+/-0.20 L and +0.11+/-0.30 L, and DeltaRV (residual
      volume) was -0.65+/-0.90 L and -0.71+/-0.81 L (all p<0.01). Post hoc analyses
      showed significant responses for SGRQ, 6MWD and RV in patients with both
      heterogeneous and homogeneous emphysema. CONCLUSIONS: LVR coil treatment results
      in significant clinical improvements in patients with severe emphysema, with a
      good safety profile and sustained results for up to 1 year. TRIAL REGISTRATION
      NUMBER: NCT01328899.

PMID- 24891329
TI  - Was the flu drug zanamivir a breakthrough or money for old rope?

PMID- 24891330
TI  - Implication of Epstein-Barr virus infection in disease-specific autoreactive B
      cell activation in ectopic lymphoid structures of Sjogren's syndrome.
AB  - OBJECTIVE: To examine whether the B cell tropic gamma-herpesvirus Epstein-Barr
      virus (EBV) is aberrantly expressed in its latent and lytic forms within ectopic
      lymphoid structures (ELS) in the salivary glands of patients with Sjogren's
      syndrome (SS), and to investigate the relationship between EBV dysregulation, B
      cell activation, in situ differentiation of autoreactive plasma cells, disease
      specific autoantibody production, and cytotoxicity. METHODS: Latent and lytic EBV
      infection in the salivary glands of 28 patients with SS and 38 patients with
      nonspecific chronic sialadenitis (NSCS), characterized for the presence or
      absence of ELS, was investigated by reverse transcription-polymerase chain
      reaction, in situ hybridization, and immunohistochemical/immunofluorescence
      staining. Glandular versus synovial production of anti-Ro 52, anti-citrullinated
      protein antibodies (ACPAs), and anti-EBV peptide antibodies was analyzed in situ
      or in vivo in human SS/SCID and human rheumatoid arthritis/SCID mouse chimeras.
      RESULTS: EBV dysregulation within inflammatory infiltrates was observed
      exclusively in ELS+ SS salivary gland tissue, as revealed by latent EBV infection
      and lytic EBV infection in B cells and plasma cells, respectively. Conversely,
      epithelial latent membrane protein 2A expression was observed in both patients
      with SS and patients with NSCS. Importantly, perifollicular plasma cells
      displaying Ro 52 immunoreactivity were frequently infected by EBV. Furthermore,
      ELS-containing SS salivary gland tissue that was transplanted into SCID mice
      supported the production of anti-Ro 52/anti-La 48 and anti-EBV antibodies but not
      ACPAs. Analysis of CD4+ and CD8+ T cell localization and granzyme B expression
      demonstrated that the persistence of EBV in ELS-containing SS salivary glands was
      associated with follicular exclusion of CD8+ T cells and impaired CD8-mediated
      cytotoxicity. CONCLUSION: Active EBV infection is selectively associated with ELS
      in the salivary glands of patients with SS and appears to contribute to local
      growth and differentiation of disease-specific autoreactive B cells.

PMID- 24891331
TI  - Enhanced lipid isomer separation in human plasma using reversed-phase UPLC with
      ion-mobility/high-resolution MS detection.
AB  - An ultraperformance LC (UPLC) method for the separation of different lipid
      molecular species and lipid isomers using a stationary phase incorporating
      charged surface hybrid (CSH) technology is described. The resulting enhanced
      separation possibilities of the method are demonstrated using standards and human
      plasma extracts. Lipids were extracted from human plasma samples with the Bligh
      and Dyer method. Separation of lipids was achieved on a 100 * 2.1 mm inner
      diameter CSH C18 column using gradient elution with aqueous-acetonitrile
      isopropanol mobile phases containing 10 mM ammonium formate/0.1% formic acid
      buffers at a flow rate of 0.4 ml/min. A UPLC run time of 20 min was routinely
      used, and a shorter method with a 10 min run time is also described. The method
      shows extremely stable retention times when human plasma extracts and a variety
      of biofluids or tissues are analyzed [intra-assay relative standard deviation
      (RSD) <0.385% and <0.451% for 20 and 10 min gradients, respectively (n = 5);
      interassay RSD <0.673% and <0.763% for 20 and 10 min gradients, respectively (n =
      30)]. The UPLC system was coupled to a hybrid quadrupole orthogonal acceleration
      time-of-flight mass spectrometer, equipped with a traveling wave ion-mobility
      cell. Besides demonstrating the separation for different lipids using the
      chromatographic method, we demonstrate the use of the ion-mobility MS platform
      for the structural elucidation of lipids. The method can now be used to elucidate
      structures of a wide variety of lipids in biological samples of different
      matrices. 

PMID- 24891332
TI  - Identification of four novel genes contributing to familial elevated plasma HDL
      cholesterol in humans.
AB  - While genetic determinants strongly influence HDL cholesterol (HDLc) levels, most
      genetic causes underlying variation in HDLc remain unknown. We aimed to identify
      novel rare mutations with large effects in candidate genes contributing to
      extreme HDLc in humans, utilizing family-based Mendelian genetics. We performed
      next-generation sequencing of 456 candidate HDLc-regulating genes in 200
      unrelated probands with extremely low (<=10th percentile) or high (>=90th
      percentile) HDLc. Probands were excluded if known mutations existed in the
      established HDLc-regulating genes ABCA1, APOA1, LCAT, cholesteryl ester transfer
      protein (CETP), endothelial lipase (LIPG), and UDP-N-acetyl-alpha-D
      galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GALNT2). We
      identified 93 novel coding or splice-site variants in 72 candidate genes. Each
      variant was genotyped in the proband's family. Family-based association analyses
      were performed for variants with sufficient power to detect significance at P <
      0.05 with a total of 627 family members being assessed. Mutations in the genes
      glucokinase regulatory protein (GCKR), RNase L (RNASEL), leukocyte immunoglobulin
      like receptor 3 (LILRA3), and dynein axonemal heavy chain 10 (DNAH10) segregated
      with elevated HDLc levels in families, while no mutations associated with low
      HDLc. Taken together, we have identified mutations in four novel genes that may
      play a role in regulating HDLc levels in humans. 

PMID- 24891333
TI  - Absence of Nceh1 augments 25-hydroxycholesterol-induced ER stress and apoptosis
      in macrophages.
AB  - An excess of cholesterol and/or oxysterols induces apoptosis in macrophages,
      contributing to the development of advanced atherosclerotic lesions. In foam
      cells, these sterols are stored in esterified forms, which are hydrolyzed by two
      enzymes: neutral cholesterol ester hydrolase 1 (Nceh1) and hormone-sensitive
      lipase (Lipe). A deficiency in either enzyme leads to accelerated growth of
      atherosclerotic lesions in mice. However, it is poorly understood how the
      esterification and hydrolysis of sterols are linked to apoptosis. Remarkably,
      Nceh1-deficient thioglycollate-elicited peritoneal macrophages (TGEMs), but not
      Lipe-deficient TGEMs, were more susceptible to apoptosis induced by oxysterols,
      particularly 25-hydroxycholesterol (25-HC), and incubation with 25-HC caused
      massive accumulation of 25-HC ester in the endoplasmic reticulum (ER) due to its
      defective hydrolysis, thereby activating ER stress signaling such as induction of
      CCAAT/enhancer-binding protein-homologous protein (CHOP). These changes were
      nearly reversed by inhibition of ACAT1. In conclusion, deficiency of Nceh1
      augments 25-HC-induced ER stress and subsequent apoptosis in TGEMs. In addition
      to reducing the cholesteryl ester content of foam cells, Nceh1 may protect
      against the pro-apoptotic effect of oxysterols and modulate the development of
      atherosclerosis. 

PMID- 24891336
TI  - Brief Report: Involvement of TNFRSF11A molecular defects in autoinflammatory
      disorders.
AB  - OBJECTIVE: Autoinflammatory disorders are caused by a primary dysfunction of the
      innate immune system. Among these disorders are hereditary recurrent fevers,
      which are characterized by recurrent episodes of fever and inflammatory
      manifestations affecting multiple tissues. Hereditary recurrent fevers often lack
      objective diagnostic criteria, thereby hampering the identification of disease
      causing genes. This study was undertaken to identify a gene responsible for
      hereditary recurrent fevers. METHODS: Copy number variations and point mutations
      were sought by array-comparative genomic hybridization and polymerase chain
      reaction sequencing, respectively. Serum cytokine levels were measured using
      Luminex technology. The effect of TNFRSF11A molecular defects on NF-kappaB
      signaling in cells expressing wild-type and mutated forms of the receptor was
      evaluated by luciferase assay. RESULTS: A patient with multiple congenital
      anomalies and hereditary recurrent fever was found to carry a de novo
      heterozygous complex chromosomal rearrangement encompassing a duplication of
      TNFRSF11A, a gene known to regulate fever in rodents. We also identified a
      heterozygous frameshift mutation (p.Met416Cysfs*110) in TNFRSF11A in a mother and
      daughter with isolated hereditary recurrent fever. This mutation was associated
      with increased secretion of several inflammatory cytokines (tumor necrosis factor
      alpha [TNFalpha], interleukin-18 [IL-18], IL-1 receptor antagonist, interferon
      gamma) and altered the biologic effects of the receptor on NF-kappaB signaling.
      The disease in the patients described herein exhibits striking clinical
      similarities to TNF receptor-associated periodic syndrome, another hereditary
      recurrent fever involving a gene of the same family (TNFRSF1A). CONCLUSION: The
      involvement of TNFRSF11A in hereditary recurrent fever highlights the key role of
      this receptor in innate immunity. The present results also suggest that TNFRSF11A
      screening could serve as a new diagnostic test for autoinflammatory disorders.

PMID- 24891334
TI  - Novel lysophosphoplipid receptors: their structure and function.
AB  - It is now accepted that lysophospholipids (LysoGPs) have a wide variety of
      functions as lipid mediators that are exerted through G protein-coupled receptors
      (GPCRs) specific to each lysophospholipid. While the roles of some LysoGPs, such
      as lysophosphatidic acid and sphingosine 1-phosphate, have been thoroughly
      examined, little is known about the roles of several other LysoGPs, such as
      lysophosphatidylserine (LysoPS), lysophosphatidylthreonine,
      lysophosphatidylethanolamine, lysophosphatidylinositol (LPI), and
      lysophosphatidylglycerol. Recently, a GPCR was found for LPI (GPR55) and three
      GPCRs (GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3) were found for LysoPS. In this
      review, we focus on these newly identified GPCRs and summarize the actions of
      LysoPS and LPI as lipid mediators. 

PMID- 24891335
TI  - Minimally oxidized LDL inhibits macrophage selective cholesteryl ester uptake and
      native LDL-induced foam cell formation.
AB  - Scavenger receptor-mediated uptake of oxidized LDL (oxLDL) is thought to be the
      major mechanism of foam cell generation in atherosclerotic lesions. Recent data
      has indicated that native LDL is also capable of contributing to foam cell
      formation via low-affinity receptor-independent LDL particle pinocytosis and
      selective cholesteryl ester (CE) uptake. In the current investigation, Cu(2+)
      induced LDL oxidation was found to inhibit macrophage selective CE uptake.
      Impairment of selective CE uptake was significant with LDL oxidized for as little
      as 30 min and correlated with oxidative fragmentation of apoB. In contrast, LDL
      aggregation, LDL CE oxidation, and the enhancement of scavenger receptor-mediated
      LDL particle uptake required at least 3 h of oxidation. Selective CE uptake did
      not require expression of the LDL receptor (LDL-R) and was inhibited similarly by
      LDL oxidation in LDL-R(-/-) versus WT macrophages. Inhibition of selective uptake
      was also observed when cells were pretreated or cotreated with minimally oxidized
      LDL, indicating a direct inhibitory effect of this oxLDL on macrophages.
      Consistent with the effect on LDL CE uptake, minimal LDL oxidation almost
      completely prevented LDL-induced foam cell formation. These data demonstrate a
      novel inhibitory effect of mildly oxidized LDL that may reduce foam cell
      formation in atherosclerosis. 

PMID- 24891337
TI  - Management based on exhaled nitric oxide levels adjusted for atopy reduces asthma
      exacerbations in children: A dual centre randomized controlled trial.
AB  - While several randomized control trials (RCTs) have evaluated the use of
      fractional exhaled nitric oxide (FeNO) to improve asthma outcomes, none used FeNO
      cut-offs adjusted for atopy, a determinant of FeNO levels. In a dual center RCT,
      we assessed whether a treatment strategy based on FeNO levels, adjusted for
      atopy, reduces asthma exacerbations compared with the symptoms-based management
      (controls). Children with asthma from hospital clinics of two hospitals were
      randomly allocated to receive an a-priori determined treatment hierarchy based on
      symptoms or FeNO levels. There was a 2-week run-in period and they were then
      reviewed 10 times over 12-months. The primary outcome was the number of children
      with exacerbations over 12-months. Sixty-three children were randomized (FeNO =
      31, controls = 32); 55 (86%) completed the study. Although we did achieve our
      planned sample size, significantly fewer children in the FeNO group (6 of 27) had
      an asthma exacerbation compared to controls (15 of 28), P = 0.021; number to
      treat for benefit = 4 (95% CI 3-24). There was no difference between groups for
      any secondary outcomes (quality of life, symptoms, FEV1 ). The final daily
      inhaled corticosteroids (ICS) dose was significantly (P = 0.037) higher in the
      FeNO group (median 400 ug, IQR 250-600) compared to the controls (200, IQR100
      400). Taking atopy into account when using FeNO to tailor asthma medications is
      likely beneficial in reducing the number of children with severe exacerbations at
      the expense of increased ICS use. However, the strategy is unlikely beneficial
      for improving asthma control. A larger study is required to confirm or refute our
      findings.

PMID- 24891339
TI  - Temple syndrome: improving the recognition of an underdiagnosed chromosome 14
      imprinting disorder: an analysis of 51 published cases.
AB  - Chromosome 14 harbours an imprinted locus at 14q32. Maternal uniparental disomy
      of chromosome 14, paternal deletions and loss of methylation at the intergenic
      differentially methylated region (IG-DMR) result in a human phenotype of low
      birth weight, hypotonia, early puberty and markedly short adult stature. The
      analysis of the world literature of 51 cases identifies the key features that
      will enhance diagnosis and potentially improve treatment. We found a median birth
      weight SD score (SDS) of -1.88 and median adult final height of -2.04 SDS.
      Hypotonia and motor delay were reported in 93% and 83% of cases, respectively.
      Early puberty was reported in 86% of cases with the mean age of menarche at 10
      years and 2 months of age. Small hands and feet were reported frequently (87% and
      96%, respectively). Premature birth was common (30%) and feeding difficulties
      frequently reported (n = 22). There was evidence of mildly reduced intellectual
      ability (measured IQ 75-95). Obesity was reported in 49% of cases, and three
      patients developed type 2 diabetes mellitus. Two patients were reported to have
      recurrent hypoglycaemia, and one of these patients was subsequently demonstrated
      to be growth hormone deficient and started replacement therapy. We propose the
      use of the name 'Temple syndrome' for this condition and suggest that improved
      diagnosis and long-term monitoring, especially of growth and cardiovascular risk
      factors, is required. 

PMID- 24891343
TI  - Neratinib Graduates to I-SPY 3.

PMID- 24891344
TI  - Palbociclib ups PFS in HER2-/ER+ breast cancer.

PMID- 24891338
TI  - SLC39A5 mutations interfering with the BMP/TGF-beta pathway in non-syndromic high
      myopia.
AB  - BACKGROUND: High myopia, with the characteristic feature of refractive error, is
      one of the leading causes of blindness worldwide. It has a high heritability, but
      only a few causative genes have been identified and the pathogenesis is still
      unclear. METHODS: We used whole genome linkage and exome sequencing to identify
      the causative mutation in a non-syndromic high myopia family. Direct Sanger
      sequencing was used to screen the candidate gene in additional sporadic cases or
      probands. Immunofluorescence was used to evaluate the expression pattern of the
      candidate gene in the whole process of eye development. Real-time quantitative
      PCR and immunoblot was used to investigate the functional consequence of the
      disease-associated mutations. RESULTS: We identified a nonsense mutation
      (c.141C>G:p.Y47*) in SLC39A5 co-segregating with the phenotype in a non-syndromic
      severe high myopia family. The same nonsense mutation (c.141C>G:p.Y47*) was
      detected in a sporadic case and a missense mutation (c.911T>C:p.M304T) was
      identified and co-segregated in another family by screening additional cases.
      Both disease-associated mutations were not found in 1276 control individuals.
      SLC39A5 was abundantly expressed in the sclera and retina across different stages
      of eye development. Furthermore, we found that wild-type, but not disease
      associated SLC39A5 inhibited the expression of Smadl, a key phosphate protein in
      the downstream of the BMP/TGF-beta (bone morphogenic protein/transforming growth
      factor-beta) pathway. CONCLUSIONS: Our study reveals that loss-of-function
      mutations of SLC39A5 are associated with the autosome dominant non-syndromic high
      myopia, and interference with the BMP/TGF-beta pathway may be one of the
      molecular mechanisms for high myopia.

PMID- 24891345
TI  - UV light accelerates melanoma metastasis.

PMID- 24891346
TI  - FGFR inhibitor works in multiple cancers.

PMID- 24891348
TI  - Q&A:Brian Kennedy on aging and cancer.

PMID- 24891349
TI  - New nanomedicines may better target tumors.

PMID- 24891360
TI  - Second-generation ALK inhibitors: filling the non "MET" gap.
AB  - Ceritinib and other second-generation inhibitors have demonstrated promising
      anticancer activity in anaplastic lymphoma kinase (ALK)-positive non-small cell
      lung cancer (NSCLC). Specifically, they can overcome resistance due to certain
      gatekeeper mutations acquired following crizotinib exposure. These agents now
      provide new options for the management of ALK-positive NSCLC.

PMID- 24891361
TI  - Soil amendments that slow cancer growth.
AB  - The recognition that the tumor microenvironment contributes to tumor survival,
      growth, and response to therapy provides the rationale for considering it a
      therapeutic target. The article by Alspach and colleagues in this issue provides
      evidence that p38MAPK acts posttranscriptionally to promote the tumor-permissive
      secretory phenotype of both cancer-associated and senescent fibroblasts, and that
      p38MAPK inhibitors already in clinical trials have significant therapeutic
      potential.

PMID- 24891362
TI  - VEGFA genomic amplification tailors treatment of HCCs with sorafenib.
AB  - In this issue of Cancer Discovery, Horwitz and colleagues identified a subtype of
      hepatocelluar carcinoma (HCC) bearing VEGFA genomic amplification that is
      particularly sensitive to VEGFA inhibition and is also more sensitive to
      sorafenib treatment. Taken conjointly, these data suggest that VEGFA genomic
      amplification can be used as a biomarker for personalized treatment of HCC with
      sorafenib.

PMID- 24891363
TI  - EML4-ALK fusions: propelling cancer but creating exploitable chaperone
      dependence.
AB  - The crystal structure of a conserved tubulin-binding region of the EML1 protein
      reveals a highly atypical fold in one of its beta-propeller domains. Disruption
      of the EML1 core region domain in many of the oncogenic EML4-ALK fusion protein
      variants that drive non-small cell lung cancer explains their dependence on the
      HSP90 molecular chaperone, provides a basis to allow more precise patient
      stratification for therapy, and suggests a more general model for other oncogenic
      fusion proteins.

PMID- 24891364
TI  - Surviving metabolic stress: of mice (squirrels) and men.
AB  - Understanding how cancer cells survive harsh environmental conditions may be
      fundamental to eradicating malignancies proven to be impervious to treatment.
      Nutrient and growth factor deprivation, hypoxia, and low pH create metabolic
      demands that require cellular adaptations to sustain energy levels. Protein
      synthesis is one of the most notable consumers of energy. Mounting evidence
      implicates exquisite control of protein synthesis as a survival mechanism for
      both normal and malignant cells. In this commentary, we discuss the role of
      protein synthesis in energy conservation in cancer and focus on elongation factor
      2 kinase, a downstream component of the PI3K-AKT pathway that behaves as a
      critical checkpoint in energy consumption. .

PMID- 24891385
TI  - Analysis of nonlinear intensity attenuation in bright-field TEM images for
      correct 3D reconstruction of the density in micron-sized materials.
AB  - To obtain the correct tomographic reconstruction of micron-sized materials, the
      nonlinear intensity attenuation of bright-field transmission electron microscopy
      (BF-TEM) images was analyzed as a function of the sample thickness using a high
      voltage electron microscope. The intensity attenuation was precisely measured
      relative to the projection thickness of carbon microcoils (CMCs) at acceleration
      voltages of 400-1000 kV using objective apertures (OAs) with radii of 2.1-28 nm(
      1). The results show that the nonlinearity is strongly dependent on the OA size
      and the acceleration voltage. The influence of nonlinearity on tomographic
      reconstructions was also examined using a specially developed 360 degrees -tilt
      sample holder. Sliced images of the reconstructed volumes indicated that an
      increase in the nonlinearity caused artificial fluctuations in the internal
      density of materials and inaccurate shapes of the objects in more significant
      cases. Conditions sufficient for reconstruction with the correct density have
      been estimated to be 0.67 of the minimum electron transmittance, and for
      reconstructions with correct shapes, 0.4. This information enables foreseeing the
      quality of the reconstruction from a single BF-TEM image prior to the tilt-series
      acquisition. As a result to demonstrate the appropriateness of these conditions,
      a CMC with a diameter of 3.7 um was reconstructed successfully; i.e. not only the
      shape but also the internal density were correctly reproduced using electron
      tomography. 

PMID- 24891387
TI  - Dense waters of the Weddell and Scotia Seas: recent changes in properties and
      circulation.
AB  - The densest waters in the Atlantic overturning circulation are sourced at the
      periphery of Antarctica, especially the Weddell Sea, and flow northward via
      routes that involve crossing the complex bathymetry of the Scotia Arc. Recent
      observations of significant warming of these waters along much of the length of
      the Atlantic have highlighted the need to identify and understand the time
      varying formation and export processes, and the controls on their properties and
      flows. Here, we review recent developments in understanding of the processes that
      control the changing flux of water through the main export route from the Weddell
      Sea into the Scotia Sea, and the transformations of the waters within the Scotia
      Sea and environs. We also present a synopsis of recent findings that relate to
      the climatic change of dense water properties within the Weddell Sea itself, in
      the context of known Atlantic-scale changes. Among the most significant findings
      are the discovery that the warming of waters exported from the Weddell Sea has
      been accompanied by a significant freshening, and that the episodic nature of the
      overflow into the Scotia Sea is markedly wind-controlled and can lead to
      significantly enhanced abyssal stratification. Key areas for focusing future
      research effort are outlined. 

PMID- 24891386
TI  - SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development.
AB  - Small ubiquitin-like modifier (SUMO1-3) conjugation plays a critical role in
      embryogenesis. Embryos deficient in the SUMO-conjugating enzyme Ubc9 die at the
      early postimplantation stage. Sumo1(-/-) mice are viable, as SUMO2/3 can
      compensate for most SUMO1 functions. To uncover the role of SUMO2/3 in
      embryogenesis, we generated Sumo2- and Sumo3-null mutant mice. Here, we report
      that Sumo3(-/-) mice were viable, while Sumo2(-/-) embryos exhibited severe
      developmental delay and died at approximately embryonic day 10.5 (E10.5). We also
      provide evidence that SUMO2 is the predominantly expressed SUMO isoform.
      Furthermore, although Sumo2(+/-) and Sumo2(+/-);Sumo3(+/-) mice lacked any overt
      phenotype, only 2 Sumo2(+/-);Sumo3(-/-) mice were found at birth in 35 litters
      after crossing Sumo2(+/-);Sumo3(+/-) with Sumo3(-/-) mice, and these rare mice
      were considerably smaller than littermates of the other genotypes. Thus, our
      findings suggest that expression levels and not functional differences between
      SUMO2 and SUMO3 are critical for normal embryogenesis.

PMID- 24891388
TI  - An observing system simulation for Southern Ocean carbon dioxide uptake.
AB  - The Southern Ocean is critically important to the oceanic uptake of anthropogenic
      CO2. Up to half of the excess CO2 currently in the ocean entered through the
      Southern Ocean. That uptake helps to maintain the global carbon balance and
      buffers transient climate change from fossil fuel emissions. However, the future
      evolution of the uptake is uncertain, because our understanding of the dynamics
      that govern the Southern Ocean CO2 uptake is incomplete. Sparse observations and
      incomplete model formulations limit our ability to constrain the monthly and
      annual uptake, interannual variability and long-term trends. Float-based sampling
      of ocean biogeochemistry provides an opportunity for transforming our
      understanding of the Southern Ocean CO2 flux. In this work, we review current
      estimates of the CO2 uptake in the Southern Ocean and projections of its response
      to climate change. We then show, via an observational system simulation
      experiment, that float-based sampling provides a significant opportunity for
      measuring the mean fluxes and monitoring the mean uptake over decadal scales. 

PMID- 24891389
TI  - Ocean processes at the Antarctic continental slope.
AB  - The Antarctic continental shelves and slopes occupy relatively small areas, but,
      nevertheless, are important for global climate, biogeochemical cycling and
      ecosystem functioning. Processes of water mass transformation through sea ice
      formation/melting and ocean-atmosphere interaction are key to the formation of
      deep and bottom waters as well as determining the heat flux beneath ice shelves.
      Climate models, however, struggle to capture these physical processes and are
      unable to reproduce water mass properties of the region. Dynamics at the
      continental slope are key for correctly modelling climate, yet their small
      spatial scale presents challenges both for ocean modelling and for observational
      studies. Cross-slope exchange processes are also vital for the flux of nutrients
      such as iron from the continental shelf into the mixed layer of the Southern
      Ocean. An iron-cycling model embedded in an eddy-permitting ocean model reveals
      the importance of sedimentary iron in fertilizing parts of the Southern Ocean.
      Ocean gliders play a key role in improving our ability to observe and understand
      these small-scale processes at the continental shelf break. The Gliders:
      Excellent New Tools for Observing the Ocean (GENTOO) project deployed three
      Seagliders for up to two months in early 2012 to sample the water to the east of
      the Antarctic Peninsula in unprecedented temporal and spatial detail. The glider
      data resolve small-scale exchange processes across the shelf-break front (the
      Antarctic Slope Front) and the front's biogeochemical signature. GENTOO
      demonstrated the capability of ocean gliders to play a key role in a future multi
      disciplinary Southern Ocean observing system. 

PMID- 24891390
TI  - Does the sensitivity of Southern Ocean circulation depend upon bathymetric
      details?
AB  - The response of the major ocean currents to changes in wind stress forcing is
      investigated with a series of idealized, but eddy-permitting, model simulations.
      Previously, ostensibly similar models have shown considerable variation in the
      oceanic response to changing wind stress forcing. Here, it is shown that a major
      reason for these differences in model sensitivity is subtle modification of the
      idealized bathymetry. The key bathymetric parameter is the extent to which the
      strong eddy field generated in the circumpolar current can interact with the
      bottom water formation process. The addition of an embayment, which insulates
      bottom water formation from meridional eddy fluxes, acts to stabilize the deep
      ocean density and enhances the sensitivity of the circumpolar current. The degree
      of interaction between Southern Ocean eddies and Antarctic shelf processes may
      thereby control the sensitivity of the Southern Ocean to change. 

PMID- 24891391
TI  - Rapid invasion of anthropogenic CO2 into the deep circulation of the Weddell
      Gyre.
AB  - Data are presented for total carbon dioxide (TCO2), oxygen and nutrients from 14
      cruises covering two repeat sections across the Weddell Gyre, from 1973 to 2010.
      Assessments of the rate of increase in anthropogenic CO2 (Cant) are made at three
      locations. Along the Prime Meridian, TCO2 is observed to steadily increase in the
      bottom water. Accompanying changes in silicate, nitrate and oxygen confirm the
      non-steady state of the Weddell circulation. The rate of increase in TCO2 of
      +0.12+/-0.05 MUmol kg(-1) yr(-1) therefore poses an upper limit to the rate of
      increase in Cant. By contrast, the bottom water located in the central Weddell
      Sea exhibits no significant increase in TCO2, suggesting that this water is less
      well ventilated at the southern margins of the Weddell Sea. At the tip of the
      Antarctic Peninsula (i.e. the formation region of the bottom water found at the
      Prime Meridian), the high rate of increase in TCO2 over time observed at the
      lowest temperatures suggests that nearly full equilibration occurs with the
      anthropogenic CO2 of the atmosphere. This observation constitutes rare evidence
      for the possibility that ice cover is not a major impediment for uptake of Cant
      in this prominent deep water formation region. 

PMID- 24891392
TI  - The ocean's role in polar climate change: asymmetric Arctic and Antarctic
      responses to greenhouse gas and ozone forcing.
AB  - In recent decades, the Arctic has been warming and sea ice disappearing. By
      contrast, the Southern Ocean around Antarctica has been (mainly) cooling and sea
      ice extent growing. We argue here that interhemispheric asymmetries in the mean
      ocean circulation, with sinking in the northern North Atlantic and upwelling
      around Antarctica, strongly influence the sea-surface temperature (SST) response
      to anthropogenic greenhouse gas (GHG) forcing, accelerating warming in the Arctic
      while delaying it in the Antarctic. Furthermore, while the amplitude of GHG
      forcing has been similar at the poles, significant ozone depletion only occurs
      over Antarctica. We suggest that the initial response of SST around Antarctica to
      ozone depletion is one of cooling and only later adds to the GHG-induced warming
      trend as upwelling of sub-surface warm water associated with stronger surface
      westerlies impacts surface properties. We organize our discussion around 'climate
      response functions' (CRFs), i.e. the response of the climate to 'step' changes in
      anthropogenic forcing in which GHG and/or ozone-hole forcing is abruptly turned
      on and the transient response of the climate revealed and studied. Convolutions
      of known or postulated GHG and ozone-hole forcing functions with their respective
      CRFs then yield the transient forced SST response (implied by linear response
      theory), providing a context for discussion of the differing warming/cooling
      trends in the Arctic and Antarctic. We speculate that the period through which we
      are now passing may be one in which the delayed warming of SST associated with
      GHG forcing around Antarctica is largely cancelled by the cooling effects
      associated with the ozone hole. By mid-century, however, ozone-hole effects may
      instead be adding to GHG warming around Antarctica but with diminished amplitude
      as the ozone hole heals. The Arctic, meanwhile, responding to GHG forcing but in
      a manner amplified by ocean heat transport, may continue to warm at an
      accelerating rate. 

PMID- 24891393
TI  - The Southern Ocean, carbon and climate.

PMID- 24891394
TI  - Freshwater fluxes in the Weddell Gyre: results from delta18O.
AB  - Full-depth measurements of delta(18)O from 2008 to 2010 enclosing the Weddell
      Gyre in the Southern Ocean are used to investigate the regional freshwater
      budget. Using complementary salinity, nutrients and oxygen data, a four-component
      mass balance was applied to quantify the relative contributions of meteoric water
      (precipitation/glacial input), sea-ice melt and saline (oceanic) sources.
      Combination of freshwater fractions with velocity fields derived from a box
      inverse analysis enabled the estimation of gyre-scale budgets of both freshwater
      types, with deep water exports found to dominate the budget. Surface net sea-ice
      melt and meteoric contributions reach 1.8% and 3.2%, respectively, influenced by
      the summer sampling period, and -1.7% and +1.7% at depth, indicative of a
      dominance of sea-ice production over melt and a sizable contribution of shelf
      waters to deep water mass formation. A net meteoric water export of approximately
      37 mSv is determined, commensurate with local estimates of ice sheet outflow and
      precipitation, and the Weddell Gyre is estimated to be a region of net sea-ice
      production. These results constitute the first synoptic benchmarking of sea-ice
      and meteoric exports from the Weddell Gyre, against which future change
      associated with an accelerating hydrological cycle, ocean climate change and
      evolving Antarctic glacial mass balance can be determined. 

PMID- 24891395
TI  - The Southern Ocean in the Coupled Model Intercomparison Project phase 5.
AB  - The Southern Ocean is an important part of the global climate system, but its
      complex coupled nature makes both its present state and its response to projected
      future climate forcing difficult to model. Clear trends in wind, sea-ice extent
      and ocean properties emerged from multi-model intercomparison in the Coupled
      Model Intercomparison Project phase 3 (CMIP3). Here, we review recent analyses of
      the historical and projected wind, sea ice, circulation and bulk properties of
      the Southern Ocean in the updated Coupled Model Intercomparison Project phase 5
      (CMIP5) ensemble. Improvements to the models include higher resolutions, more
      complex and better-tuned parametrizations of ocean mixing, and improved
      biogeochemical cycles and atmospheric chemistry. CMIP5 largely reproduces the
      findings of CMIP3, but with smaller inter-model spreads and biases. By the end of
      the twenty-first century, mid-latitude wind stresses increase and shift
      polewards. All water masses warm, and intermediate waters freshen, while bottom
      waters increase in salinity. Surface mixed layers shallow, warm and freshen,
      whereas sea ice decreases. The upper overturning circulation intensifies, whereas
      bottom water formation is reduced. Significant disagreement exists between models
      for the response of the Antarctic Circumpolar Current strength, for reasons that
      are as yet unclear. 

PMID- 24891396
TI  - Meridional displacement of the Antarctic Circumpolar Current.
AB  - Observed long-term warming trends in the Southern Ocean have been interpreted as
      a sign of increased poleward eddy heat transport or of a poleward displacement of
      the entire Antarctic Circumpolar Current (ACC) frontal system. The two-decade
      long record from satellite altimetry is an important source of information for
      evaluating the mechanisms governing these trends. While several recent studies
      have used sea surface height contours to index ACC frontal displacements, here
      altimeter data are instead used to track the latitude of mean ACC transport.
      Altimetric height contours indicate a poleward trend, regardless of whether they
      are associated with ACC fronts. The zonally averaged transport latitude index
      shows no long-term trend, implying that ACC meridional shifts determined from sea
      surface height might be associated with large-scale changes in sea surface height
      more than with localized shifts in frontal positions. The transport latitude
      index is weakly sensitive to the Southern Annular Mode, but is uncorrelated with
      El Nino/Southern Oscillation. 

PMID- 24891397
TI  - Changes in the ventilation of the southern oceans.
AB  - Changes in the ventilation of the southern oceans over the past few decades are
      examined using ocean measurements of CFC-12 and model simulations. Analysis of
      CFC-12 measurements made between the late 1980s and late 2000s reveal large-scale
      coherent changes in the ventilation, with a decrease in the age of subtropical
      Subantarctic Mode Waters (SAMW) and an increase in the age of Circumpolar Deep
      Waters. The decrease in SAMW age is consistent with the observed increase in wind
      stress curl and strength of the subtropical gyres over the same period. A
      decrease in the age of SAMW is also found in Community Climate System Model
      version 4 perturbation experiments where the zonal wind stress is increased. This
      decrease is due to both more rapid transport along isopycnals and the movement of
      the isopycnals. These results indicate that the intensification of surface winds
      in the Southern Hemisphere has caused large-scale coherent changes in the
      ventilation of the southern oceans. 

PMID- 24891398
TI  - Biological response to millennial variability of dust and nutrient supply in the
      Subantarctic South Atlantic Ocean.
AB  - Fluxes of lithogenic material and fluxes of three palaeo-productivity proxies
      (organic carbon, biogenic opal and alkenones) over the past 100,000 years were
      determined using the (230)Th-normalization method in three sediment cores from
      the Subantarctic South Atlantic Ocean. Features in the lithogenic flux record of
      each core correspond to similar features in the record of dust deposition in the
      EPICA Dome C ice core. Biogenic fluxes correlate with lithogenic fluxes in each
      sediment core. Our preferred interpretation is that South American dust, most
      probably from Patagonia, constitutes a major source of lithogenic material in
      Subantarctic South Atlantic sediments, and that past biological productivity in
      this region responded to variability in the supply of dust, probably due to
      biologically available iron carried by the dust. Greater nutrient supply as well
      as greater nutrient utilization (stimulated by dust) contributed to Subantarctic
      productivity during cold periods, in contrast to the region south of the
      Antarctic Polar Front (APF), where reduced nutrient supply during cold periods
      was the principal factor limiting productivity. The anti-phased patterns of
      productivity on opposite sides of the APF point to shifts in the physical supply
      of nutrients and to dust as cofactors regulating productivity in the Southern
      Ocean.

PMID- 24891399
TI  - High-density lipoprotein as a modulator of platelet and coagulation responses.
AB  - Platelets and coagulation factors are involved in the process of haemostasis,
      which ensures undisturbed blood flow upon vessel wall damage. However, excessive
      platelet aggregation and/or coagulation may lead to arterial or venous
      thrombosis. Pro-atherogenic lipoproteins, including native and oxidized low
      density lipoprotein (LDL), are associated with an increased susceptibility to
      thrombosis. In contrast, numerous epidemiological studies have established an
      inverse correlation between high-density lipoprotein (HDL) levels and the risk
      for thrombosis. In addition to its role in reverse cholesterol transport, HDL
      also interacts with platelets, the coagulation cascade, and the vascular
      endothelium. Native HDL prevents platelet hyperreactivity by limiting
      intraplatelet cholesterol overload, as well as by modulating platelet signalling
      pathways after binding platelet HDL receptors such as scavenger receptor class B
      type I (SR-BI) and apoER2'. The antithrombotic properties of native HDL are also
      related to the suppression of the coagulation cascade and stimulation of clot
      fibrinolysis. Furthermore, HDL stimulates the endothelial production of nitric
      oxide and prostacyclin, which are potent inhibitors of platelet activation. Thus,
      HDL's antithrombotic actions are multiple and therefore, raising HDL may be an
      important therapeutic strategy to reduce the risk of arterial and venous
      thrombosis. 

PMID- 24891400
TI  - Atheroprotective role of high-density lipoprotein (HDL)-associated sphingosine-1
      phosphate (S1P).
AB  - Numerous epidemiological studies documented an inverse relationship between
      plasma high-density lipoprotein (HDL) cholesterol levels and the extent of
      atherosclerotic disease. However, clinical interventions targeting HDL
      cholesterol failed to show clinical benefits with respect to cardiovascular risk
      reduction, suggesting that HDL components distinct from cholesterol may account
      for anti-atherogenic effects attributed to this lipoprotein. Sphingosine-1
      phosphate (S1P)-a lysosphingolipid exerting its biological activity via binding
      to specific G protein-coupled receptors and regulating a wide array of biological
      responses in a variety of different organs and tissues including the
      cardiovascular system-has been identified as an integral constituent of HDL
      particles. In the present review, we discuss current evidence from
      epidemiological studies, experimental approaches in vitro, and animal models of
      atherosclerosis, suggesting that S1P contributes to atheroprotective effects
      exerted by HDL particles. 

PMID- 24891403
TI  - Preface:measurement technology and data analysis for fixed gamma probe networks
      and mobile systems.

PMID- 24891401
TI  - CXCR3-independent actions of the CXC chemokine CXCL10 in the infarcted myocardium
      and in isolated cardiac fibroblasts are mediated through proteoglycans.
AB  - AIMS: The CXC chemokine CXCL10 is up-regulated in the infarcted myocardium and
      limits cardiac fibrosis by inhibiting growth factor-mediated fibroblast
      migration. CXCL10 signals by binding to its receptor CXCR3; however, recently
      CXCR3-independent CXCL10 actions have been suggested. Our study explores the role
      of CXCR3 signalling in myocardial infarction and investigates its involvement in
      mediating the anti-fibrotic effects of CXCL10. METHODS AND RESULTS: Wild-type and
      CXCR3 null mice underwent reperfused infarction protocols. CXCL10 was markedly
      induced in the infarct; in contrast, expression of the other two CXCR3 ligands,
      CXCL9 and CXCL11 was extremely low. CXCR3 loss did not affect scar size,
      geometric ventricular remodelling, collagen deposition, and systolic dysfunction
      of the infarcted heart. CXCR3 null mice had increased peak neutrophil recruitment
      and delayed myofibroblast infiltration in the infarcted heart, but exhibited
      comparable myocardial expression of pro-inflammatory cytokines and chemokines. In
      vitro, CXCL10 did not modulate Transforming Growth Factor (TGF)-beta signalling,
      but inhibited basic fibroblast growth factor (bFGF)-induced cardiac fibroblast
      migration in both wild-type and CXCR3 null cells. Treatment of fibroblasts with
      heparinase and chondroitinase to cleave glycosaminoglycan chains abrogated the
      inhibitory effects of CXCL10 on cell migration. CONCLUSION: CXCR3 signalling does
      not critically regulate cardiac remodelling and dysfunction following myocardial
      infarction. The anti-fibrotic effects of CXCL10 in the healing infarct and in
      isolated cardiac fibroblasts are CXCR3-independent and may be mediated through
      proteoglycan signalling. Thus, administration of CXCR3-defective forms of CXCL10
      may be an effective anti-fibrotic strategy in the remodelling myocardium without
      activating a potentially injurious, CXCR3-driven T cell response.

PMID- 24891404
TI  - Selection of neutron-absorbing materials to improve the low-energy response of a
      Zr-based extended neutron monitor using Monte Carlo simulations.
AB  - Monte Carlo simulations have been carried out using the FLUKA code to improve the
      neutron ambient dose equivalent [H*(10)] response of the ZReC (zirconium-lined
      portable neutron counter responding satisfactorily to neutrons up to 1 GeV) by
      introducing various neutron absorbers in the system such as cadmium, gadolinium,
      natural boron, enriched (10)B and borated polythene. It was found that ZReC can
      be effectively used as a portable neutron monitor by introducing any one of the
      following perforated layers: 5 mm thick natural boron, 0.5 mm thick enriched
      (10)B or 1 cm high-density polythene mixed with 50 % boron by weight. The
      integral response of the instrument was also calculated for some typical
      reference neutron fields. The relative ambient dose equivalent response of the
      said system is also found comparable with that of the existing LINUS neutron
      monitor. 

PMID- 24891405
TI  - Diagnostic reference levels and patient doses in computed tomography examinations
      in Greece.
AB  - The purpose of this study is to present a national survey that was performed in
      Greece for the establishment of national Dose Reference Levels (DRLs) for seven
      common adult Computed Tomography (CT) examinations. Volumetric computed
      tomography dose index and dose-length product values were collected from the post
      data page of 65 'modern' systems that incorporate tube current modulation.
      Moreover, phantom dose measurements on 26 'older' systems were performed.
      Finally, the effective dose to the patient from a typical acquisition during
      these examinations was estimated. The suggested national DRLs are generally
      comparable with respective published values from similar European studies, with
      the exception of sinuses CT, which presents significantly higher values. This
      fact, along with the large variation of the systems' dose values that were
      observed even for scanners of the same type, indicates a need for further patient
      protection optimisation without compromising the clinical outcome. 

PMID- 24891406
TI  - Electron spin resonance dating of megafauna from Lagoa dos Porcos, Piaui, Brazil.
AB  - Excavations performed at Lagoa dos Porcos site revealed a vast amount of extinct
      mammal fossil remains, becoming one of the richest palaeontological occurrences
      in the Serra da Capivara National Park region, a UNESCO World Heritage. Although
      anatomic and taxonomic aspects of extinct Quaternary mammals are relatively well
      known, chronologic information for deposits is rare. In this context, electron
      spin resonance (ESR) dating of megafauna samples provides important information
      for establishing a chronological background. This work presents the ESR dating of
      two teeth, one of Gomphotheriidae and other of Toxodontinae. Dose-response curves
      of each sample were constructed using spectra acquired with a JEOL FA-200 X-Band
      spectrometer resulting in equivalent dose (De) of 220 +/- 40 Gy and 39 +/- 2 Gy
      for Toxodontinae and Gomphotheriidae tooth, respectively. The conversion of De in
      age was made using ROSY ESR dating software resulting in 26 +/- 4 and 22 +/- 3
      ka. These results place Lagoa dos Porcos fossil assemblage within the Late
      Pleistocene. These dates overlap with a period of abrupt increase in rainfall in
      northeast Brazil, and it is possible that this environmental change is related to
      the formation of this deposit.

PMID- 24891407
TI  - The use of point-of-care blood ketone monitors in the management of diabetic
      ketoacidosis in adults.

PMID- 24891408
TI  - Suspected liposarcoma of the hip by magnetic resonance imaging 3 years after
      large-volume fat grafting for buttock augmentation.

PMID- 24891409
TI  - Growth dynamics of geographically different arbuscular mycorrhizal fungal
      isolates belonging to the 'Rhizophagus clade' under monoxenic conditions.
AB  - The growth dynamics of extraradical mycelium and spore formation of 14
      "Rhizophagus" isolates from different sites in Argentina were evaluated under
      monoxenic conditions. A modified Gompertz model was used to characterize the
      development of mycelium and spores for each isolate under the same conditions.
      The lag time, maximal growth rate and total quantity of both extraradical hyphae
      and spores were determined. Wide variability among isolates was detected, and all
      growth parameters were significantly altered by fungal isolate. Discriminant
      analysis differentiated isolates primarily based on the extent of extraradical
      hyphae produced, yet such differences did not conclusively correspond to
      phylogenetic relationships among closely related isolates based on partial SSU
      sequences. Given that the "Rhizophagus" isolates were grown under controlled
      conditions for many generations, the expression of phenotypic variability could
      be attributed to genetic differences that are not completely resolved by
      phylogenetic analysis employing the small ribosomal gene. 

PMID- 24891410
TI  - New resinicolous Chaenothecopsis species from China.
AB  - Four new resinicolous species of Chaenothecopsis are described from China:
      Chaenothecopsis perforata from exudate of Rhus chinensis (Anacardiaceae), C.
      pallida from exudate of Ailanthus altissima (Simaroubaceae), C. resinophila from
      exudate of Kalopanax septemlobus (Araliaceae) and C. hunanensis from resin of
      Pinus massoniana (Pinaceae). All the new species are compared with previously
      described resinicolous mycocalicioid taxa, and several new features in these
      species are presented. The newly described species cannot always be distinguished
      by any single character, but they all possess unique combinations of
      morphological, chemical and ecological features. Several aspects in the ecology
      and evolution of boreal and tropical resinicolous species are briefly discussed. 

PMID- 24891411
TI  - Testing the "one-log-one-genet" hypothesis: methodological challenges of
      population sampling for the Hawaiian wood-decay fungus Rhodocollybia laulaha.
AB  - We test our "one-log-one-genet" sampling method for the Hawaiian mushroom
      Rhodocollybia laulaha that posits all R. laulaha mushrooms collected from a
      single log represent a single genet. We also examine the potential expansion of
      single genets beyond the confines of one log and the temporal persistence of
      genets in nature. Finally, we estimate error rates in AFLP scoring. To our
      knowledge, this is one of few examinations of naturally occurring fungal genets
      in the tropics and a novel report of AFLP error rates in fungi. Forty-six
      mushrooms from seven logs were genotyped with the IGS1 locus, two microsatellite
      loci and 184 AFLP loci from three primer pair combinations. One hundred fifty
      three mushroom collections representing the geographic range of R. laulaha were
      genotyped with the IGS1 and microsatellite loci. The probabilities of two genets
      sharing identical multilocus genotypes by chance (without actually being the same
      genet) were calculated for each genotype recovered. The data suggest that R.
      laulaha mushrooms from one log typically represent one genet, that genets might
      expand beyond the confines of a single log and that a single genet may persist in
      a collecting site for as much as 13 y. We offer initial evidence to support the
      "one-log-one genet" sampling method and the idea that R. laulaha vegetative
      expansion and persistence in nature might be common. In addition, we caution
      against exclusive use of AFLP loci for identifying fungal genets due to
      relatively high error rates in scoring. 

PMID- 24891412
TI  - Austroboletus amazonicus sp. nov. and Fistulinella campinaranae var.
      scrobiculata, two commonly occurring boletes from a forest dominated by
      Pseudomonotes tropenbosii (Dipterocarpaceae) in Colombian Amazonia.
AB  - Two boletes that frequently form fruiting bodies in Pseudomonotes tropenbosii
      forests are described from Colombian Amazonia. One is a new species of
      Austroboletus here described as A. amazonicus and the other one is Fistulinella
      campinaranae var. scrobiculata Singer, which is a new record for Colombia.
      Macromorphological, micromorphological and habitat data for these species are
      provided as well as DNA sequence data of the internal transcribed spacer (ITS)
      regions and the D1/D2 domains of the large subunit (LSU) ribosomal DNA. 

PMID- 24891413
TI  - Multigene phylogeny of the Phallales (Phallomycetidae, Agaricomycetes) focusing
      on some previously unrepresented genera.
AB  - Phylogenetic relationships within the Phallales were estimated via combined
      sequences: nuclear ribosomal large subunit (LSU), second largest subunit of RNA
      polymerase (rpb2), and mitochondrial ATPase subunit 6 (atp6). The ingroup is
      represented by 62 taxa comprising 18 genera and 44 species, including members of
      the Clathraceae, Claustulaceae, Gastrosporiaceae, Lysuraceae, Phallaceae and
      Protophallaceae. Sixty-one new sequences were generated, including tropical and
      subtropical taxa. This is one of the first studies discussing the phylogenetic
      placement of Abrachium, Aseroe, Blumenavia, Gastrosporium, Jansia and
      Xylophallus. Gastrosporiaceae was demonstrated to be sister to Phallaceae and an
      emended description of the order is presented. Aseroe was demonstrated to be
      polyphyletic and as a result, A. arachnoidea is transferred to Lysurus. 

PMID- 24891414
TI  - Genomewide mutation dynamic within a long-lived individual of Armillaria gallica.
AB  - Mutation is the ultimate source of all genetic variation in populations and yet
      they remain unobservable and buried in the past. Long-lived individuals of
      Armillaria gallica, a common opportunistic fungal pathogen of tree roots in
      temperate forests of the northern hemisphere, provide a spatial context for
      examining the mutational dynamic. Each individual of A. gallica arises in a
      single mating between two haploid gametes and the resulting diploid then grows
      vegetatively to occupy a discrete spatial territory often including many adjacent
      tree root systems. In effect, this leaves a spatial record of growth over time
      within which mutations can be localized. To identify mutations, the entire
      genomes of three spatially separated samples of one individual of A. gallica
      approximately 200 * 60 m were sequenced and compared. In this comparison,
      mutations and regions of loss of heterozygosity (LOH) were identified then
      assayed in another 20 isolates from the same individual by conventional PCR and
      Sanger sequencing. The genotype network of all mutations and LOH were without
      internal conflict. Further, the spatial pattern of genotypes was nonrandom and
      appeared to reflect the vegetative expansion leading to the present-day
      individual. The results reflect the spectrum of spontaneous mutation in nature
      and provide insight into cellular generation times. 

PMID- 24891416
TI  - Common, unsightly and until now undescribed: Fumiglobus pieridicola sp. nov., a
      sooty mold infesting Pieris japonica from western North America.
AB  - Sooty molds (Capnodiaceae) are saprotrophs on the surfaces of leaves, and they
      take their nutrients from honeydew exuded by sap-sucking insects. We describe and
      illustrate the sooty mold Fumiglobus pieridicola sp. nov., which, to the dismay
      of gardeners, forms a thick black mycelial coating on the leaves and twigs of
      ornamental Japanese andromeda (Pieris japonica) in western North America. As a
      mitosporic species with a pycnidium that lacks an elongated neck and has at most
      a rudimentary stalk, the species belongs in the genus Fumiglobus. Although
      locally common, we found no specimens identified under Fumiglobus or its synonyms
      in regional herbaria and no record of any similar fungus in host indices. Our
      species differs from others in Fumiglobus in having smaller pycnidia and conidia
      and in having intercalary as well as apical pycnidia. We determined partial 18S
      and 28S ribosomal gene sequences for F. pieridicola, the first for any Fumiglobus
      species. Sequence analysis provides strong bootstrap support for including
      Fumiglobus within Capnodiaceae. We also determined 18S and 28S sequences for the
      type species of the mitosporic genus Conidiocarpus, also in Capnodiaceae. We
      confirm that Conidiocarpus is the anamorph of Phragmocapnias. Following the rules
      of nomenclatural priority, we propose the new combinations Conidiocarpus
      asiaticus, Conidiocarpus betle, Conidiocarpus callitris, Conidiocarpus
      fuliginodes, Conidiocarpus heliconiae, Conidiocarpus imperspicuus and
      Conidiocarpus siamensis. We hope that describing the mystery fungus from our
      region and providing sequences for its molecular identification will lead to new
      studies on its biology and distribution.

PMID- 24891417
TI  - Characterization and phylogenetic analysis of the mating-type loci in the asexual
      ascomycete genus Ulocladium.
AB  - The genus Ulocladium is thought to be strictly asexual. Mating-type (MAT) loci
      regulate sexual reproduction in fungi and their study may help to explain the
      apparent lack of sexual reproduction in Ulocladium. We sequenced the full length
      of two MAT genes in 26 Ulocladium species and characterized the entire MAT
      idiomorphs plus flanking regions of Ulocladium botrytis. The MAT1-1 ORF encodes a
      protein with an alpha-box motif by the MAT1-1-1 gene and the MAT1-2 ORF encodes a
      protein with an HMG box motif by the MAT1-2-1 gene. Both MAT1-1-1 and MAT1-2-1
      genes were detected in a single strain of every species. Moreover, the results of
      RT-PCR revealed that both MAT genes are expressed in all 26 Ulocladium species.
      This demonstrates that MAT genes of Ulocladium species might be functional and
      that they have the potential for sexual reproduction. Phylogenies based on MAT
      genes were compared with GAPDH and Alt a 1 phylograms in Ulocladium using maximum
      parsimony (MP) and Bayesian analysis. The MAT genealogies and the non-MAT trees
      displayed different topologies, indicating that MAT genes are unsuitable
      phylogenetic markers at the species level in Ulocladium. Furthermore, the
      conflicting topologies between MAT1-1-1 and MAT1-2-1 phylogeny indicate separate
      evolutionary events for the two MAT genes. However, the intergeneric phylogeny of
      four closely allied genera (Ulocladium, Alternaria, Cochliobolus, Stemphylium)
      based on MAT alignments demonstrated that MAT genes are suitable for phylogenetic
      analysis among allied genera. 

PMID- 24891418
TI  - Clarification of generic and species boundaries for Metarhizium and related fungi
      through multigene phylogenetics.
AB  - The genus Metarhizium historically refers to green-spored asexual insect
      pathogenic fungi. Through culturing and molecular methods, Metarhizium has been
      linked to Metacordyceps sexual states. Historically fungal nomenclature has
      allowed separate names for the different life stages of pleomorphic fungi.
      However, with the move to one name for one fungus regardless of life stage, there
      is a need to determine which name is correct. For Metarhizium the situation is
      complicated by the fact that Metacordyceps sexual states are interspersed among
      additional asexual genera, including Pochonia, Nomuraea and Paecilomyces.
      Metarhizium has priority as the earliest available name, but delimiting the
      boundaries of this genus remains problematic. To clarify relationships among
      these taxa we have obtained representative material for each genus and
      established a molecular dataset of the protein-coding genes BTUB, RPB1, RPB2 and
      TEF. The resulting phylogeny supports Metarhizium combining the majority of
      species recognized in Metacordyceps as well as the green-spored Nomuraea species
      and those in the more recently described genus Chamaeleomyces. Pochonia is
      polyphyletic, and we restrict the definition of this genus to those species
      forming a monophyletic clade with P. chlamydosporia, and the excluded species are
      transferred to Metapochonia gen. nov. It is our hope that this unified concept of
      sexual and asexual states in Metarhizium will foster advances in communication
      and understanding the unique ecologies of the associated species. 

PMID- 24891419
TI  - A revision of the Alpova diplophloeus complex in North America.
AB  - Alpova diplophloeus (Boletales, Paxillaceae) is the only currently recognized
      Alpova in North America with a brownish peridium, large gleba chambers and which
      forms ectomycorrhizas with Alnus. However, A. diplophloeus as currently
      circumscribed is a polyphyletic species, with at least three distinct genetic
      entities. Using a combination of molecular and morphological characters, we
      examined the type collections of A. diplophloeus, as well as species synonymized
      with it, including A. cinnamomeus and Rhizopogon parvisporus. We also examined
      several other collections of A. diplophloeus complex basidiomata. We describe A.
      diplophloeus sensu stricto; we also resurrect A. cinnamomeus, synonymized with R.
      parvisporus and describe a new species, A. concolor, from the complex. 

PMID- 24891420
TI  - New species of Cordana and epitypification of the genus.
AB  - Two interesting fungi belonging to the genus Cordana have been isolated recently
      in Spain from plant debris. Both are proposed here as new species, described and
      illustrated. Cordana mercadiana sp. nov. produces 0-1-septate conidia, with a
      prominent basal scar. Cordana verruculosa sp. nov. differs from the other species
      of the genus by its unique combination of aseptate, verruculose and small
      conidia. Both species are compared morphologically with other species of Cordana
      and their identities supported by the analysis of rDNA sequences. LSU sequence
      analysis revealed the congeneric relationship of Cordana and Pseudobotrytis; the
      members of both genera are in a well supported monophyletic lineage that appears
      to be related to the Coniochaetales but remains incertae sedis within the
      Sordariomycetes. To establish nomenclatural stability of the genus Cordana, an
      isolate of C. pauciseptata is designed here as epitype and the two species of
      Pseudobotrytis are transferred to Cordana. A dichotomous key is provided to
      identify the currently accepted species of Cordana. 

PMID- 24891421
TI  - Genetic architecture and evolution of the mating type locus in fusaria that cause
      soybean sudden death syndrome and bean root rot.
AB  - Fusarium tucumaniae is the only known sexually reproducing species among the
      seven closely related fusaria that cause soybean sudden death syndrome (SDS) or
      bean root rot (BRR). In a previous study, laboratory mating of F. tucumaniae
      yielded recombinant ascospore progeny but required two mating-compatible strains,
      indicating that it is heterothallic. To assess the reproductive mode of the other
      SDS and BRR fusaria, and their potential for mating, whole-genome sequences of
      two SDS and one BRR pathogen were analyzed to characterize their mating type
      (MAT) loci. This bioinformatic approach identified a MAT1-1 idiomorph in F.
      virguliforme NRRL 22292 and MAT1-2 idiomorphs in F. tucumaniae NRRL 34546 and F.
      azukicola NRRL 54364. Alignments of the MAT loci were used to design PCR primers
      within the conserved regions of the flanking genes APN1 and SLA2, which enabled
      primer walking to obtain nearly complete sequences of the MAT region for six MAT1
      1 and five MAT1-2 SDS/BRR fusaria. As expected, sequences of the highly divergent
      4.7 kb MAT1-1 and 3.7 kb MAT1-2 idiomorphs were unalignable. However, sequences
      of the respective idiomorphs and those that flank MAT1-1 and MAT1-2 were highly
      conserved. In addition to three genes at MAT1-1 (MAT1-1-1, MAT1-1-2, MAT1-1-3)
      and two at MAT1-2 (MAT1-2-1, MAT1-2-3), the MAT loci of the SDS/BRR fusaria also
      include a putative gene predicted to encode for a 252 amino acid protein of
      unknown function. Alignments of the MAT1-1-3 and MAT1-2-1 sequences were used to
      design a multiplex PCR assay for the MAT loci. This assay was used to screen DNA
      from 439 SDS/BRR isolates, which revealed that each isolate possessed MAT1-1 or
      MAT1-2, consistent with heterothallism. Both idiomorphs were represented among
      isolates of F. azukicola, F. brasiliense, F. phaseoli and F. tucumaniae, whereas
      isolates of F. virguliforme and F. cuneirostrum were only MAT1-1 and F.
      crassistipitatum were only MAT1-2. Finally, nucleotide sequence data from the
      RPB1 and RPB2 genes were used to date the origin of the SDS/BRR group, which was
      estimated to have occurred about 0.75 Mya (95% HPD interval: 0.27, 1.68) in the
      mid-Pleistocene, long before the domestication of the common bean or soybean. 

PMID- 24891422
TI  - An eight-gene molecular phylogeny of the Kickxellomycotina, including the first
      phylogenetic placement of Asellariales.
AB  - Kickxellomycotina is a recently described subphylum encompassing four zygomycete
      orders (Asellariales, Dimargaritales, Harpellales, Kickxellales). These fungi are
      united by the formation of disciform septal pores containing lenticular plugs.
      Morphological diversification and life history evolution has made the
      relationships within and among the four orders difficult to resolve on those
      grounds alone. Here we infer the phylogeny of the Kickxellomycotina based on an
      eight-gene supermatrix including both ribosomal rDNA (18S, 28S, 5.8S) and protein
      sequences (MCM7, TSR1, RPB1, RPB2, beta-tubulin). The results of this study
      demonstrate that Kickxellomycotina is monophyletic and related to members of the
      Zoopagomycotina. Eight unique clades are distinguished in the Kickxellomycotina,
      including the four defined orders (Asellariales, Dimargaritales, Harpellales,
      Kickxellales) as well as four genera previously placed within two of these orders
      (Barbatospora, Orphella, Ramicandelaber, Spiromyces). Dimargaritales and
      Ramicandelaber are the earliest diverging members of the subphylum, although the
      relationship between these taxa remains uncertain. The remaining six clades form
      a monophyletic group, with Barbatospora diverging first. The next split divides
      the remaining members of the subphylum into two subclades: (i) Asellariales and
      Harpellales and (ii) Kickxellales, Orphella and Spiromyces. Estimation of
      ancestral states for four potentially informative morphological and ecological
      characters reveals that arthropod endosymbiosis might have been an important
      factor in the early evolution of the Kickxellomycotina. 

PMID- 24891423
TI  - Acidomelania panicicola gen. et sp. nov. from switchgrass roots in acidic New
      Jersey pine barrens.
AB  - A new genus, Acidomelania, is described based on molecular phylogenetic analyses
      and ecological and morphological characters. Isolated from switchgrass roots in
      acidic and oligotrophic New Jersey pine barrens in this study, Acidomelania
      likely has a global distribution because its internal transcribed spacer (ITS)
      sequence has high similarity with a number of GenBank sequences resulted from
      various ecological studies. Apparently these samples all were from roots of
      plants that lived in acidic, nutrient-poor environments. Phylogenetic analyses
      based on ITS, LSU and ACT sequence data strongly supported the fact that
      Acidomelania isolates formed a monophyletic clade in Helotiales, distinct from
      any known taxa. Phylogenetically Acidomelania is closely related to Loramyces,
      Mollisia and Phialocephala fortinii, Acephala applanata species complex (PAC),
      the dark septate endophytes. Acidomelania also can be distinguished from
      Loramyces and Mollisia by its association with living grass roots. While taxa in
      PAC also are root endophytes, they have more complex phialid arrangement than
      Acidomelania. Results from this work will facilitate ecological and evolutionary
      studies on root-associated fungi. 

PMID- 24891424
TI  - Four new bioluminescent taxa of Mycena sect. Calodontes from Peninsular Malaysia.
AB  - Three new species and one new variety of bioluminescent Mycena collected from
      Peninsular Malaysia are described herein. All new species belong to Mycena sect.
      Calodontes in what is known as the Mycena pura complex. Comprehensive
      descriptions, photographs, illustrations and comparisons with phenetically
      similar species are provided. Molecular sequences data from the nuclear internal
      transcribed spacers (ITS-1 and ITS-2, including the 5.8S rRNA) were used to infer
      relationships within sect. Calodontes. Axenic cultures were obtained to provide
      data on culture morphology. This is the first published photographic
      documentation of bioluminescent basidiomes of members of Mycena sect. Calodontes.
      Also, this addition brings the total known bioluminescent fungi to 77 species. 

PMID- 24891425
TI  - Secondary metabolites from Penicillium corylophilum isolated from damp buildings.
AB  - Indoor exposure to the spores and mycelial fragments of fungi that grow on damp
      building materials can result in increased non-atopic asthma and upper
      respiratory disease. The mechanism appears to involve exposure to low doses of
      fungal metabolites. Penicillium corylophilum is surprisingly common in damp
      buildings in USA, Canada and western Europe. We examined isolates of P.
      corylophilum geographically distributed across Canada in the first comprehensive
      study of secondary metabolites of this fungus. The sesquiterpene phomenone, the
      meroterpenoids citreohybridonol and andrastin A, koninginin A, E and G, three new
      alpha pyrones and four new isochromans were identified from extracts of culture
      filtrates. This is the first report of koninginins, meroterpenoids and alpha
      pyrones from P. corylophilum. These secondary metabolite data support the removal
      of P. corylophilum from Penicillium section Citrina and suggest that further
      taxonomic studies are required on this species. 

PMID- 24891426
TI  - The utility of MMPI-2-RF substantive scales in prediction of negative treatment
      outcomes in a community mental health center.
AB  - This study examined the utility of the Minnesota Multiphasic Personality
      Inventory-2-Restructured Form (MMPI-2-RF) substantive scales in the prediction of
      premature termination and therapy no-shows while controlling for other relevant
      predictors in a university-based community mental health center, a sample at high
      risk of both premature termination and no-show appointments. Participants
      included 457 individuals seeking services from a university-based psychology
      clinic. Results indicated that Juvenile Conduct Problems (JCP) predicted
      premature termination and Behavioral/Externalizing Dysfunction and JCP predicted
      number of no-shows, when accounting for initial severity of illness, personality
      disorder diagnosis, therapist experience, and other related MMPI-2-RF scales. The
      MMPI-2-RF Aesthetic-Literary Interests scale also predicted number of no-shows.
      Recommendations for applying these findings in clinical practice are discussed. 

PMID- 24891427
TI  - Factorial invariance of the Five-Factor Model Rating Form across gender.
AB  - The Five-Factor Model Rating Form (FFMRF) provides a brief, one-page assessment
      of the Five-Factor Model. An important and unique aspect of the FFMRF is that it
      is the only brief measure that includes scales for the 30 facets proposed by
      Costa and McCrae. The current study builds on existing validity support for the
      FFMRF by evaluating its factorial invariance across gender within a sample of 699
      undergraduate students. Consistent with other measures of the Five-Factor Model,
      men scored lower than women on the domains of neuroticism, extraversion,
      agreeableness, and conscientiousness but slightly higher on openness. The novel
      contribution of the current study is the use of exploratory structural equation
      modeling to determine that the FFMRF displayed a five-factor structure that
      demonstrated strong measurement invariance across gender. This factorial
      invariance adds important support for the validity of the FFMRF as a self-report
      measure as it indicates that the scores assess the same latent constructs in men
      and women. Although future work is needed to clarify some facet-level findings
      and evaluate for potential predictive biases, the present results add to the
      increasing body of research supporting the validity of the FFMRF as a self-report
      measure of personality. 

PMID- 24891428
TI  - Pristinamycin: old drug, new tricks?
AB  - Osteoarticular infections with Gram positive bacteria present an increasing
      challenge in an era of multidrug-resistant organisms. Prolonged intravenous
      antibiotic treatment is often required, with associated risks, costs and
      difficulties with administration; a safe, effective oral option would be ideal
      for this indication. Pristinamycin, an oral streptogramin antibiotic with
      bactericidal activity against Gram positive organisms including methicillin
      resistant Staphylococcus aureus, has been used for over 50 years in Europe for
      the treatment of osteoarticular infections. We review the published evidence for
      the treatment of native bone and prosthesis-related osteoarticular infections
      with pristinamycin. 

PMID- 24891429
TI  - Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non
      pregnant women with uncomplicated Plasmodium falciparum infection in Burkina
      Faso.
AB  - OBJECTIVES: Mefloquine/artesunate has recently been developed as a fixed-dose
      combination, providing a promising rescue/alternative treatment for malaria
      during pregnancy. However, limited data are available on the effect of pregnancy
      on its pharmacokinetic properties. This study was conducted to assess the
      pharmacokinetic properties of mefloquine/carboxymefloquine and
      artesunate/dihydroartemisinin in pregnant and non-pregnant women with
      uncomplicated malaria. METHODS: Twenty-four women in their second and third
      trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All
      patients were treated for uncomplicated Plasmodium falciparum malaria with a
      standard fixed-dose combination of oral mefloquine and artesunate one daily over
      3 days. Frequent blood samples were collected before treatment and at scheduled
      times post-dose for the drug measurements and pharmacokinetic analyses. The study
      was registered at www.clinicaltrials.gov (identifier: NCT00701961). RESULTS: The
      total median exposure to mefloquine and dihydroartemisinin was not significantly
      different between the pregnant and non-pregnant women (P>0.05). There was a trend
      of higher exposure to mefloquine in the pregnant women, but this difference did
      not reach statistical significance (656700 versus 542400 h * ng/mL; P=0.059).
      However, the total exposure to carboxymefloquine was 49% lower during pregnancy
      (735600 versus 1499000 h * ng/mL; P<0.001) and the total drug exposure to
      artesunate was 42% higher during pregnancy (89.0 versus 62.9 h * ng/mL; P=0.039)
      compared with non-pregnant controls. CONCLUSIONS: The plasma levels of mefloquine
      and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant
      women, but there were significant differences in carboxymefloquine and artesunate
      exposure. The data presented here do not warrant a dose adjustment in pregnant
      patients, but an extensive analysis of the data could provide a better
      understanding of these findings.

PMID- 24891430
TI  - Amphotericin B transfer to CSF following intravenous administration of liposomal
      amphotericin B.
AB  - OBJECTIVES: Although amphotericin B (AmB) and its lipid formulations are used for
      the treatment of fungal infections of the CNS, the kinetics of AmB in the CSF
      after intravenous administration of liposomal amphotericin B (LAmB) are not well
      characterized. PATIENTS AND METHODS: From 14 paediatric haemato-oncological
      patients (aged 0.4-19.5 years, median 7.6 years), we obtained 30 CSF samples by
      means of routine punctures (performed for intrathecal treatment of the underlying
      diseases) at different timepoints after the prophylactic intravenous infusion of
      LAmB (AmBisome, 3 mg/kg/day). Concurrent serum samples were obtained to calculate
      the transfer rates. An HPLC method was used for AmB detection. RESULTS: CSF
      levels of AmB 1-100 h after the intravenous infusion of LAmB were between 10 and
      120 ng/mL, except in one case with a level of 529 ng/mL. Concurrent serum levels
      were about 1000-fold higher, ranging between 3 and 75 MUg/mL. CSF levels did not
      show a clear time-dependent concentration profile, but remained at a steady-state
      for longer than 48 h after infusion. The transfer rate ranged from 0.02% to 0.92%
      (median 0.13%) and correlated significantly (r=0.801, P<0.001) with increasing
      time after infusion. CONCLUSIONS: After the intravenous administration of LAmB,
      AmB CSF levels were low, confirming published animal data. CSF levels remained at
      a steady-state level for longer than 48 h. As indicated by published post mortem
      data, higher levels in brain tissue, which would be necessary for the successful
      treatment of CNS infections, might be possible.

PMID- 24891431
TI  - Adverse effects associated with ethanol catheter lock solutions: a systematic
      review.
AB  - BACKGROUND: Antimicrobial lock therapy has been widely utilized internationally
      for the prevention and management of intravascular catheter-related bloodstream
      infections. One of the agents commonly utilized for lock therapy is ethanol.
      However, a systematic review of adverse events associated with ethanol locks has
      not been published. METHODS: PubMed was searched to collect articles published
      from May 2003 through March 2014. The bibliographies of relevant articles were
      also reviewed. RESULTS: In vitro studies of the mechanical properties of
      catheters after ethanol immersion have revealed changes predominantly in
      polyurethane catheters and to a lesser extent in silicone and Carbothane
      catheters. An elution of polymers from polyurethane and Carbothane catheters has
      been observed at the ethanol concentrations used in ethanol lock therapy. Ethanol
      above a concentration of 28% leads to plasma protein precipitation. Ethanol locks
      were associated with catheter occlusion in 11 studies and independently increased
      the risk of thrombosis compared with heparin lock in a randomized trial. Six
      studies noted abnormalities in catheter integrity, including one case leading to
      catheter embolization. Of note, five of these studies involved silicone
      catheters. Ethanol lock use was associated with systemic side effects in 10
      studies and possible side effects in one additional study. Four studies noted
      liver function test abnormalities, predominantly transaminase elevation, related
      to ethanol lock use. However, a prospective study did not find any difference in
      the risk of doubling the transaminase level above the normal range during use of
      ethanol locks compared with not using an ethanol lock. CONCLUSIONS: The use of
      ethanol locks has been associated with structural changes in catheters, as well
      as the elution of molecules from the catheter polymers. Clinical studies have
      revealed systemic toxicity, increased catheter occlusion and breaches in catheter
      integrity.

PMID- 24891432
TI  - Frequent carriage of resistance mechanisms to beta-lactams and biofilm formation
      in Haemophilus influenzae causing treatment failure and recurrent otitis media in
      young children.
AB  - OBJECTIVES: Non-typeable Haemophilus influenzae are a major cause of acute otitis
      media (AOM), including chronic and recurrent otitis in young children. The
      objective of this study was to determine whether non-typeable H. influenzae
      isolates causing these infections produce biofilms and carry resistance
      mechanisms to beta-lactams. METHODS: A collection of 48 H. influenzae isolates
      was obtained by tympanocentesis or from otorrhoea samples from individual
      patients <3 years of age and diagnosed with recurrent or treatment failure AOM.
      Each isolate was surveyed for the presence of blaTEM genes, amino acid
      substitutions in the transpeptidase domain of penicillin-binding protein 3 (PBP3)
      and biofilm formation in microtitre plates. RESULTS: In 43 of the 48 isolates
      (89.6%), at least one of the three tested conditions was identified: biofilm
      formation (83.3%) and resistance mechanisms to beta-lactams (33.3%),
      modifications in the transpeptidase domain of PBP3 being the most prevalent
      (22.9%), followed by beta-lactamase production (10.4%). Additionally, 13 (27.1%)
      isolates had two or more of these three traits. In relation to biofilm formation,
      those isolates with an amoxicillin MIC <= 0.5 mg/L had higher optical density
      values than isolates with an amoxicillin MIC >= 1 mg/L (Mann-Whitney U-test,
      P=0.048). CONCLUSIONS: These findings suggest that the successful treatment of
      non-typeable H. influenzae causing chronic and recurrent AOM in young children
      may be compromised by the high biofilm-forming capacity of the isolates and the
      presence of beta-lactam resistance mechanisms, particularly PBP3 mutations.

PMID- 24891433
TI  - KATP channel as well as SGLT1 participates in GIP secretion in the diabetic
      state.
AB  - Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from
      intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic
      beta-cells are glucose-responsive and equipped with a similar glucose-sensing
      apparatus that includes glucokinase and an ATP-sensitive K(+) (KATP) channel
      comprising KIR6.2 and sulfonylurea receptor 1. In absorptive epithelial cells and
      enteroendocrine cells, sodium glucose co-transporter 1 (SGLT1) is also known to
      play an important role in glucose absorption and glucose-induced incretin
      secretion. However, the glucose-sensing mechanism in K-cells is not fully
      understood. In this study, we examined the involvement of SGLT1 (SLC5A1) and the
      KATP channels in glucose sensing in GIP secretion in both normal and
      streptozotocin-induced diabetic mice. Glimepiride, a sulfonylurea, did not induce
      GIP secretion and pretreatment with diazoxide, a KATP channel activator, did not
      affect glucose-induced GIP secretion in the normal state. In mice lacking KATP
      channels (Kir6.2(-/-) mice), glucose-induced GIP secretion was enhanced compared
      with control (Kir6.2(+) (/) (+)) mice, but was completely blocked by the SGLT1
      inhibitor phlorizin. In Kir6.2(-/-) mice, intestinal glucose absorption through
      SGLT1 was enhanced compared with that in Kir6.2(+) (/) (+) mice. On the other
      hand, glucose-induced GIP secretion was enhanced in the diabetic state in
      Kir6.2(+) (/) (+) mice. This GIP secretion was partially blocked by phlorizin,
      but was completely blocked by pretreatment with diazoxide in addition to
      phlorizin administration. These results demonstrate that glucose-induced GIP
      secretion depends primarily on SGLT1 in the normal state, whereas the KATP
      channel as well as SGLT1 is involved in GIP secretion in the diabetic state in
      vivo. 

PMID- 24891435
TI  - The impact of elevation of serum uric acid level on the natural history of
      glomerular filtration rate (GFR) and its sex difference.
AB  - BACKGROUND: The impact of elevation of the serum uric acid level (SUA) on the
      natural history of glomerular filtration rate (GFR) remains controversial.
      METHODS: If elevation of SUA is a result, rather than a cause, of a decline in
      GFR, the relationship between SUA and GFR should be the same in the same
      population over years except for shifts by age-dependent reduction of GFR. We
      tested this hypothesis using data from two cohorts and a group of allopurinol
      treated patients. RESULTS: In Cohort 1 consisting of urban residents aged 40.6 +/
      9.0 years (n = 3 446), SUA was inversely correlated with estimated GFR (eGFR) in
      both men and women, and the slope of the SUA-eGFR relationship was steeper in
      women than in men. The slopes of the regression lines became significantly
      steeper after a 6-year interval in both sexes, and the change in the slope was
      larger in women. A similar sex difference in the SUA-eGFR relationship and 6-year
      change in the slope were observed in Cohort 2 consisting of rural town residents
      aged 61.7 +/- 12.2 years (n = 404). Multiple regression analyses showed that
      explanatory factors of eGFR after a 6-year interval were age and SUA at baseline
      in both cohorts, and partial regression coefficients of SUA were more negative in
      women than in men. The SUA-eGFR relationship in allopurinol-treated patients (n =
      346, 63.5 +/- 13.3 years old) was similar to that in Cohort 2. CONCLUSIONS: The
      results indicate that elevation of SUA accelerates the yearly decline in eGFR and
      that women are more susceptible to urate-induced decline in eGFR.

PMID- 24891436
TI  - Potential role of Akt signaling in chronic kidney disease.
AB  - Renal fibrosis, particularly tubulointerstitial fibrosis, is the common final
      outcome of almost all chronic kidney diseases. However, the mechanisms involved
      in the development of renal fibrosis are poorly understood. The Akt (also known
      as protein kinase B, PKB) family is serine/threonine protein kinases that play
      critical roles in regulating growth, proliferation, survival, metabolism and
      other cellular activities. Cytokines, high-glucose medium, transforming growth
      factor-beta1 or advanced glycation end-products activate Akt in different renal
      cells. Increased Akt activation has been found in experimental tubulointerstitial
      fibrosis. In addition, Akt activation is also an important node in diverse
      signaling cascades involved in kidney damage. These data give evidence for a role
      for Akt in renal fibrosis, but no reviews are available on the role of Akt in the
      process. Thus, our aim is to review the role of Akt activation and signaling in
      renal fibrosis. 

PMID- 24891434
TI  - Clocks for all seasons: unwinding the roles and mechanisms of circadian and
      interval timers in the hypothalamus and pituitary.
AB  - Adaptation to the environment is essential for survival, in all wild animal
      species seasonal variation in temperature and food availability needs to be
      anticipated. This has led to the evolution of deep-rooted physiological cycles,
      driven by internal clocks, which can track seasonal time with remarkable
      precision. Evidence has now accumulated that a seasonal change in thyroid hormone
      (TH) availability within the brain is a crucial element. This is mediated by
      local control of TH-metabolising enzymes within specialised ependymal cells
      lining the third ventricle of the hypothalamus. Within these cells, deiodinase
      type 2 enzyme is activated in response to summer day lengths, converting
      metabolically inactive thyroxine (T4) to tri-iodothyronine (T3). The availability
      of TH in the hypothalamus appears to be an important factor in driving the
      physiological changes that occur with season. Remarkably, in both birds and
      mammals, the pars tuberalis (PT) of the pituitary gland plays an essential role.
      A specialised endocrine thyrotroph cell (TSH-expressing) is regulated by the
      changing day-length signal, leading to activation of TSH by long days. This acts
      on adjacent TSH-receptors expressed in the hypothalamic ependymal cells, causing
      local regulation of deiodinase enzymes and conversion of TH to the metabolically
      active T3. In mammals, the PT is regulated by the nocturnal melatonin signal.
      Summer-like melatonin signals activate a PT-expressed clock-regulated
      transcription regulator (EYA3), which in turn drives the expression of the
      TSHbeta sub-unit, leading to a sustained increase in TSH expression. In this
      manner, a local pituitary timer, driven by melatonin, initiates a cascade of
      molecular events, led by EYA3, which translates to seasonal changes of
      neuroendocrine activity in the hypothalamus. There are remarkable parallels
      between this PT circuit and the photoperiodic timing system used in plants, and
      while plants use different molecular signals (constans vs EYA3) it appears that
      widely divergent organisms probably obey a common set of design principles. 

PMID- 24891438
TI  - Texture-shading flow interactions and perceived reflectance.
AB  - The appearance of surface texture depends on the identification of edge contours
      in an image generated by local variations in reflectance. These edges in the
      image need to be distinguished from diffuse shading gradients caused by the
      interaction of light with surface relief. To understand how the brain performs
      this separation, we generated textures with orientation flows that were initially
      congruent with the diffuse shading flow of planar surfaces. We found that
      rotating textures relative to shading increased the appearance of surface
      pigmentation, which was well explained by an increase in the variation of local
      orientation fields with increasing offset of texture gradients (Experiment 1). We
      obtained similar findings when rotating texture flow relative to the diffuse
      shading of spherical surfaces with global curvature (Experiment 2). In a second
      set of experiments, we found that perceived pigmentation of spherical surfaces
      depended on the perceived orientation of the light field; rotating images of
      spherical surfaces reduced both perceived pigmentation (Experiment 3) and
      perceived global texture contrast in an objective task (Experiment 4). The
      dependence of perceived texture on image orientation suggests that the separation
      of texture flow from shading depends on an assumed light source from above bias.
      These findings support the view that separation of texture flow from shading, and
      thus perceived pigmentation, depend not only on the local structure of
      orientation fields in an image, but also on midlevel representations of shading
      and illuminance flow.

PMID- 24891437
TI  - FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral
      iron in patients with chronic kidney disease and iron deficiency anaemia.
AB  - BACKGROUND: The optimal iron therapy regimen in patients with non-dialysis
      dependent chronic kidney disease (CKD) is unknown. METHODS: Ferinject(r)
      assessment in patients with Iron deficiency anaemia and Non-Dialysis-dependent
      Chronic Kidney Disease (FIND-CKD) was a 56-week, open-label, multicentre,
      prospective and randomized study of 626 patients with non-dialysis-dependent CKD,
      anaemia and iron deficiency not receiving erythropoiesis-stimulating agents
      (ESAs). Patients were randomized (1:1:2) to intravenous (IV) ferric
      carboxymaltose (FCM), targeting a higher (400-600 ug/L) or lower (100-200 ug/L)
      ferritin or oral iron therapy. The primary end point was time to initiation of
      other anaemia management (ESA, other iron therapy or blood transfusion) or
      haemoglobin (Hb) trigger of two consecutive values <10 g/dL during Weeks 8-52.
      RESULTS: The primary end point occurred in 36 patients (23.5%), 49 patients
      (32.2%) and 98 patients (31.8%) in the high-ferritin FCM, low-ferritin FCM and
      oral iron groups, respectively [hazard ratio (HR): 0.65; 95% confidence interval
      (CI): 0.44-0.95; P = 0.026 for high-ferritin FCM versus oral iron]. The increase
      in Hb was greater with high-ferritin FCM versus oral iron (P = 0.014) and a
      greater proportion of patients achieved an Hb increase >=1 g/dL with high
      ferritin FCM versus oral iron (HR: 2.04; 95% CI: 1.52-2.72; P < 0.001). Rates of
      adverse events and serious adverse events were similar in all groups.
      CONCLUSIONS: Compared with oral iron, IV FCM targeting a ferritin of 400-600 ug/L
      quickly reached and maintained Hb level, and delayed and/or reduced the need for
      other anaemia management including ESAs. Within the limitations of this trial, no
      renal toxicity was observed, with no difference in cardiovascular or infectious
      events. CLINICALTRIALSGOV NUMBER: NCT00994318.

PMID- 24891439
TI  - Systematic review and meta-analysis of distraction and hypnosis for needle
      related pain and distress in children and adolescents.
AB  - OBJECTIVE: To systematically review the evidence (and quality) for distraction
      and hypnosis for needle-related pain and distress in children and adolescents. To
      explore the effects of distraction characteristics (e.g., adult involvement, type
      of distracter), child age, and study risk of bias on treatment efficacy. 
      METHODS: 26 distraction and 7 hypnosis trials were included and self-report,
      observer-report, and behavioral pain intensity and distress examined. Distraction
      studies were coded for 4 intervention characteristics, and all studies coded for
      child age and study risk of bias.  RESULTS: Findings showed strong support for
      distraction and hypnosis for reducing pain and distress from needle procedures.
      The quality of available evidence was low, however. Characteristics of
      distraction interventions, child age, and study risk of bias showed some
      influence on treatment efficacy. CONCLUSIONS: Distraction and hypnosis are
      efficacious in reducing needle-related pain and distress in children. The quality
      of trials in this area needs to be improved.

PMID- 24891440
TI  - Measures of readiness to transition to adult health care for youth with chronic
      physical health conditions: a systematic review and recommendations for
      measurement testing and development.
AB  - OBJECTIVE: Review measures of readiness to transition to adult-oriented care for
      youth with chronic physical health conditions. METHODS: Identified measures via
      online searches and reference lists and reviewed methods of development,
      theoretical underpinnings, characteristics, and psychometrics. Measures were
      classified according to American Psychological Association Division 54 Evidence
      Based Assessment (EBA) Task Force criteria. Strengths and weaknesses of reviewed
      measures were described. RESULTS: 56 measures were identified, of which 10 met
      inclusion criteria for this review. 6 were disease specific and 4 were generic.
      Some psychometric properties were reported for each; none reported predictive
      validity for transition outcomes. According to EBA criteria, the 10 measures met
      criteria for "promising" assessment. CONCLUSIONS: Measurement development in
      transition readiness is still an underdeveloped area. Measures require further
      testing and new measures are needed. Recommendations include testing measures
      with larger and diverse samples, ground measures in theory, test psychometrics,
      and involve multiple stakeholders in measure development.

PMID- 24891441
TI  - RecO and RecR are necessary for RecA loading in response to DNA damage and
      replication fork stress.
AB  - RecA is central to maintaining genome integrity in bacterial cells. Despite the
      near-ubiquitous conservation of RecA in eubacteria, the pathways that facilitate
      RecA loading and repair center assembly have remained poorly understood in
      Bacillus subtilis. Here, we show that RecA rapidly colocalizes with the DNA
      polymerase complex (replisome) immediately following DNA damage or damage
      independent replication fork arrest. In Escherichia coli, the RecFOR and RecBCD
      pathways serve to load RecA and the choice between these two pathways depends on
      the type of damage under repair. We found in B. subtilis that the rapid
      localization of RecA to repair centers is strictly dependent on RecO and RecR in
      response to all types of damage examined, including a site-specific double
      stranded break and damage-independent replication fork arrest. Furthermore, we
      provide evidence that, although RecF is not required for RecA repair center
      formation in vivo, RecF does increase the efficiency of repair center assembly,
      suggesting that RecF may influence the initial stages of RecA nucleation or
      filament extension. We further identify single-stranded DNA binding protein (SSB)
      as an additional component important for RecA repair center assembly. Truncation
      of the SSB C terminus impairs the ability of B. subtilis to form repair centers
      in response to damage and damage-independent fork arrest. With these results, we
      conclude that the SSB-dependent recruitment of RecOR to the replisome is
      necessary for loading and organizing RecA into repair centers in response to DNA
      damage and replication fork arrest. 

PMID- 24891442
TI  - Analysis of the arabinose-5-phosphate isomerase of Bacteroides fragilis provides
      insight into regulation of single-domain arabinose phosphate isomerases.
AB  - Arabinose-5-phosphate isomerases (APIs) catalyze the interconversion of d
      ribulose-5-phosphate and D-arabinose-5-phosphate, the first step in the
      biosynthesis of 3-deoxy-D-manno-octulosonic acid (Kdo), an essential component of
      the lipopolysaccharide in Gram-negative bacteria. Classical APIs, such as
      Escherichia coli KdsD, contain a sugar isomerase domain and a tandem
      cystathionine beta-synthase domain. Despite substantial effort, little is known
      about structure-function relationships in these APIs. We recently reported an API
      containing only a sugar isomerase domain. This protein, c3406 from E. coli
      CFT073, has no known physiological function. In this study, we investigated a
      putative single-domain API from the anaerobic Gram-negative bacterium Bacteroides
      fragilis. This putative API (UniProt ID Q5LIW1) is the only protein encoded by
      the B. fragilis genome with significant identity to any known API, suggesting
      that it is responsible for lipopolysaccharide biosynthesis in B. fragilis. We
      tested this hypothesis by preparing recombinant Q5LIW1 protein (here referred to
      by the UniProt ID Q5LIW1), characterizing its API activity in vitro, and
      demonstrating that the gene encoding Q5LIW1 (GenBank ID YP_209877.1) was able to
      complement an API-deficient E. coli strain. We demonstrated that Q5LIW1 is
      inhibited by cytidine 5'-monophospho-3-deoxy-D-manno-2-octulosonic acid, the
      final product of the Kdo biosynthesis pathway, with a Ki of 1.91 MUM. These
      results support the assertion that Q5LIW1 is the API that supports
      lipopolysaccharide biosynthesis in B. fragilis and is subject to feedback
      regulation by CMP-Kdo. The sugar isomerase domain of E. coli KdsD, lacking the
      two cystathionine beta-synthase domains, demonstrated API activity and was
      further characterized. These results suggest that Q5LIW1 may be a suitable system
      to study API structure-function relationships.

PMID- 24891443
TI  - beta-alanine biosynthesis in Methanocaldococcus jannaschii.
AB  - One efficient approach to assigning function to unannotated genes is to establish
      the enzymes that are missing in known biosynthetic pathways. One group of such
      pathways is those involved in coenzyme biosynthesis. In the case of the
      methanogenic archaeon Methanocaldococcus jannaschii as well as most methanogens,
      none of the expected enzymes for the biosynthesis of the beta-alanine and pantoic
      acid moieties required for coenzyme A are annotated. To identify the gene(s) for
      beta-alanine biosynthesis, we have established the pathway for the formation of
      beta-alanine in this organism after experimentally eliminating other known and
      proposed pathways to beta-alanine from malonate semialdehyde, l-alanine,
      spermine, dihydrouracil, and acryloyl-coenzyme A (CoA). Our data showed that the
      decarboxylation of aspartate was the only source of beta-alanine in cell extracts
      of M. jannaschii. Unlike other prokaryotes where the enzyme producing beta
      alanine from l-aspartate is a pyruvoyl-containing l-aspartate decarboxylase
      (PanD), the enzyme in M. jannaschii is a pyridoxal phosphate (PLP)-dependent l
      aspartate decarboxylase encoded by MJ0050, the same enzyme that was found to
      decarboxylate tyrosine for methanofuran biosynthesis. A Km of ~0.80 mM for l
      aspartate with a specific activity of 0.09 MUmol min(-1) mg(-1) at 70 degrees C
      for the decarboxylation of l-aspartate was measured for the recombinant enzyme.
      The MJ0050 gene was also demonstrated to complement the Escherichia coli panD
      deletion mutant cells, in which panD encoding aspartate decarboxylase in E. coli
      had been knocked out, thus confirming the function of this gene in vivo. 

PMID- 24891447
TI  - I'm a teenage lobotomy.

PMID- 24891446
TI  - Transcription start site sequence and spacing between the -10 region and the
      start site affect reiterative transcription-mediated regulation of gene
      expression in Escherichia coli.
AB  - Reiterative transcription is a reaction catalyzed by RNA polymerase, in which
      nucleotides are repetitively added to the 3' end of a nascent transcript due to
      upstream slippage of the transcript without movement of the DNA template. In
      Escherichia coli, the expression of several operons is regulated through
      mechanisms in which high intracellular levels of UTP promote reiterative
      transcription that adds extra U residues to the 3' end of a nascent transcript
      during transcription initiation. Immediately following the addition of one or
      more extra U residues, the nascent transcripts are released from the
      transcription initiation complex, thereby reducing the level of gene expression.
      Therefore, gene expression can be regulated by internal UTP levels, which reflect
      the availability of external pyrimidine sources. The magnitude of gene regulation
      by these mechanisms varies considerably, even when control mechanisms are
      analogous. These variations apparently are due to differences in promoter
      sequences. One of the operons regulated (in part) by UTP-sensitive reiterative
      transcription in E. coli is the carAB operon, which encodes the first enzyme in
      the pyrimidine nucleotide biosynthetic pathway. In this study, we used the carAB
      operon to examine the effects of nucleotide sequence at and near the
      transcription start site and spacing between the start site and -10 region of the
      promoter on reiterative transcription and gene regulation. Our results indicate
      that these variables are important determinants in establishing the extent of
      reiterative transcription, levels of productive transcription, and range of gene
      regulation. 

PMID- 24891445
TI  - The Pseudomonas aeruginosa diguanylate cyclase GcbA, a homolog of P. fluorescens
      GcbA, promotes initial attachment to surfaces, but not biofilm formation, via
      regulation of motility.
AB  - Cyclic di-GMP is a conserved signaling molecule regulating the transitions
      between motile and sessile modes of growth in a variety of bacterial species.
      Recent evidence suggests that Pseudomonas species harbor separate intracellular
      pools of c-di-GMP to control different phenotypic outputs associated with
      motility, attachment, and biofilm formation, with multiple diguanylate cyclases
      (DGCs) playing distinct roles in these processes, yet little is known about the
      potential conservation of functional DGCs across Pseudomonas species. In the
      present study, we demonstrate that the P. aeruginosa homolog of the P.
      fluorescens DGC GcbA involved in promoting biofilm formation via regulation of
      swimming motility likewise synthesizes c-di-GMP to regulate surface attachment
      via modulation of motility, however, without affecting subsequent biofilm
      formation. P. aeruginosa GcbA was found to regulate flagellum-driven motility by
      suppressing flagellar reversal rates in a manner independent of viscosity,
      surface hardness, and polysaccharide production. P. fluorescens GcbA was found to
      be functional in P. aeruginosa and was capable of restoring phenotypes associated
      with inactivation of gcbA in P. aeruginosa to wild-type levels. Motility and
      attachment of a gcbA mutant strain could be restored to wild-type levels via
      overexpression of the small regulatory RNA RsmZ. Furthermore, epistasis analysis
      revealed that while both contribute to the regulation of initial surface
      attachment and flagellum-driven motility, GcbA and the phosphodiesterase DipA act
      within different signaling networks to regulate these processes. Our findings
      expand the complexity of c-di-GMP signaling in the regulation of the motile
      sessile switch by providing yet another potential link to the Gac/Rsm network and
      suggesting that distinct c-di-GMP-modulating signaling pathways can regulate a
      single phenotypic output. 

PMID- 24891444
TI  - Localization of the outer membrane protein OmpA2 in Caulobacter crescentus
      depends on the position of the gene in the chromosome.
AB  - The outer membrane of Gram-negative bacteria is an essential structure involved
      in nutrient uptake, protection against harmful substances, and cell growth.
      Different proteins keep the outer membrane from blebbing out by simultaneously
      interacting with it and with the cell wall. These proteins have been mainly
      studied in enterobacteria, where OmpA and the Braun and Pal lipoproteins
      stabilize the outer membrane. Some degree of functional redundancy exists between
      these proteins, since none of them is essential but the absence of two of them
      results in a severe phenotype. Caulobacter crescentus has a different strategy to
      maintain its outer membrane, since it lacks the Braun lipoprotein and Pal is
      essential. In this work, we characterized OmpA2, an OmpA-like protein, in this
      bacterium. Our results showed that this protein is required for normal stalk
      growth and that it plays a minor role in the stability of the outer membrane. An
      OmpA2 fluorescent fusion protein showed that the concentration of this protein
      decreases from the stalk to the new pole. This localization pattern is important
      for its function, and it depends on the position of the gene locus in the
      chromosome and, as a consequence, in the cell. This result suggests that little
      diffusion occurs from the moment that the gene is transcribed until the mature
      protein attaches to the cell wall in the periplasm. This mechanism reveals the
      integration of different levels of information from protein function down to
      genome arrangement that allows the cell to self-organize. 

PMID- 24891450
TI  - Incidence of brain metastasis at initial presentation of lung cancer.
AB  - BACKGROUND: No reliable estimates are available on the incidence of brain
      metastasis (BM) in cancer patients. This information is valuable for planning
      patient care and developing measures that may prevent or decrease the likelihood
      of metastatic brain disease. METHODS: We report the first population-based
      analysis on BM incidence at cancer diagnosis using the Kentucky Cancer Registry
      (KCR) and Alberta Cancer Registry (ACR). All cancer cases with BM were identified
      from KCR and ACR, with subsequent focus on metastases from lung primaries; the
      annual number of BMs at initial presentation was derived. Comparisons were made
      between Kentucky and Alberta for the stage and site of organ involvement of lung
      cancer. RESULTS: Low incidence of BM was observed in the United States until
      mandatory reporting began in 2010. Both the KCR and ACR recorded the highest
      incidence of BM from lung cancer, with total BM cases at initial presentation
      occurring at 88% and 77%, respectively. For lung cancer, stage IV was the most
      common stage at presentation for both registries and ranged from 45.9% to 57.2%.
      When BM from lung was identified, the most common synchronous organ site of
      metastasis was osseous, occurring at 28.4%. CONCLUSION: Our analysis from the
      Kentucky and Alberta cancer registries similarly demonstrated the aggressive
      nature of lung cancer and its propensity for BM at initial presentation. Besides
      widespread organ involvement, no synchronous organ site predicted BM in lung
      cancer. BM is a common and important clinical outcome, and use of registry data
      is becoming more available.

PMID- 24891448
TI  - Impact of meriolins, a new class of cyclin-dependent kinase inhibitors, on
      malignant glioma proliferation and neo-angiogenesis.
AB  - BACKGROUND: Glioblastomas are the most frequent and most aggressive primary brain
      tumors in adults. The median overall survival is limited to a few months despite
      surgery, radiotherapy, and chemotherapy. It is now clearly established that
      hyperactivity of cyclin-dependent kinases (CDKs) is one of the processes
      underlying hyperproliferation and tumoral growth. The marine natural products
      meridianins and variolins, characterized as CDK inhibitors, display a kinase
      inhibitory activity associated with cytotoxic effects. In order to improve
      selectivity and efficiency of these CDK inhibitors, a series of hybrid compounds
      called meriolins have been synthesized. METHODS: The potential antitumoral
      activity of meriolins was investigated in vitro on glioma cell lines (SW1088 and
      U87), native neural cells, and a human endothelial cell line (HUV-EC-C). The
      impact of intraperitoneal or intratumoral administrations of meriolin 15 was
      evaluated in vivo on 2 different nude mice-xenografted glioma models. RESULTS:
      Meriolins 3, 5, and 15 exhibited antiproliferative properties with nanomolar IC50
      and induced cell-cycle arrest and CDK inhibition associated with apoptotic events
      in human glioma cell lines. These meriolins blocked the proliferation rate of HUV
      EC-C through cell cycle arrest and apoptosis. In vivo, meriolin 15 provoked a
      robust reduction in tumor volume in spite of toxicity for highest doses,
      associated with inhibition of cell division, activation of caspase 3, reduction
      of CD133 cells, and modifications of the vascular architecture. CONCLUSION:
      Meriolins, and meriolin 15 in particular, exhibit antiproliferative and
      proapoptotic activities on both glioma and intratumoral endothelial cells,
      constituting key promising therapeutic lead compounds for the treatment of
      glioblastoma.

PMID- 24891453
TI  - Analysis of short-term total hospital costs and current primary cost drivers of
      coiling versus clipping for unruptured intracranial aneurysms.
AB  - BACKGROUND: No randomized controlled trial has successfully compared outcomes
      between endovascular coiling and microsurgical clipping for unruptured
      intracranial aneurysms (UIAs). OBJECTIVE: To perform a cost comparison between
      index hospitalizations of patients with UIAs treated with coil embolization or
      surgical clipping to identify the current primary drivers of costs of either
      management approach. METHODS: We obtained index hospitalization costs for 125
      cases of UIAs treated with coiling or clipping from 2010 to 2012 at our
      institution. Comparisons were stratified based on patient age, gender, aneurysm
      size, and aneurysm location. Using linear regressions, we identified clinical
      parameters that drive total hospital costs. RESULTS: 69 cases were treated with
      clipping and 56 cases were treated with coiling. Morbidity and length of stay for
      patients treated with clipping was higher. Total hospital costs and variable
      direct costs for clipping were significantly lower than for coiling (p=0.003,
      p<0.001, respectively). Fixed direct costs and fixed indirect costs for clipping
      were higher than for coiling (p<0.001, p<0.001, respectively). Variable direct
      costs comprised 50.5% and 68.6% of total hospital costs for clipping and coiling,
      respectively (p<0.001). Length of stay, aneurysm size, and patient age drove
      total hospital costs for clipping. Length of stay was a weak driver of total
      hospital costs for coiling. CONCLUSIONS: Total index hospitalization costs for
      clipping are lower than for coiling. Costs of clipping and coiling are driven by
      different clinical variables. The cost of coils and devices is the predominant
      contributor to the higher total costs of coiling.

PMID- 24891452
TI  - Sigma-1 receptor antagonism restores injury-induced decrease of voltage-gated
      Ca2+ current in sensory neurons.
AB  - Sigma-1 receptor (sigma1R), an endoplasmic reticulum-chaperone protein, can
      modulate painful response after peripheral nerve injury. We have demonstrated
      that voltage-gated calcium current is inhibited in axotomized sensory neurons. We
      examined whether sigma1R contributes to the sensory dysfunction of voltage-gated
      calcium channel (VGCC) after peripheral nerve injury through electrophysiological
      approach in dissociated rat dorsal root ganglion (DRG) neurons. Animals received
      either skin incision (Control) or spinal nerve ligation (SNL). Both sigma1R
      agonists, (+)pentazocine (PTZ) and DTG [1,3-di-(2-tolyl)guanidine], dose
      dependently inhibited calcium current (ICa) with Ba(2+) as charge carrier in
      control sensory neurons. The inhibitory effect of sigma1R agonists on ICa was
      blocked by sigma1R antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4
      methylpiperazine dihydrochloride) or BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N
      methyl-2-(dimethylamino)ethylamine dihydrobromide). PTZ and DTG showed similar
      effect on ICa in axotomized fifth DRG neurons (SNL L5). Both PTZ and DTG shifted
      the voltage-dependent activation and steady-state inactivation of VGCC to the
      left and accelerated VGCC inactivation rate in both Control and axotomized L5 SNL
      DRG neurons. The sigma1R antagonist, BD1063 (10 MUM), increases ICa in SNL L5
      neurons but had no effect on Control and noninjured fourth lumbar neurons in SNL
      rats. Together, the findings suggest that activation of sigmaR1 decreases ICa in
      sensory neurons and may play a pivotal role in pain generation. 

PMID- 24891451
TI  - Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in
      atypical meningioma.
AB  - BACKGROUND: The impact of adjuvant radiation in patients with atypical meningioma
      remains poorly defined. We sought to determine the impact of adjuvant radiation
      therapy in this population. METHODS: We identified 91 patients with World Health
      Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and
      Women's Cancer Center between 1997 and 2011. A propensity score model
      incorporating age at diagnosis, gender, Karnofsky performance status, tumor
      location, tumor size, reason for diagnosis, and era of treatment was constructed
      using logistic regression for the outcome of receipt versus nonreceipt of
      radiation therapy. Propensity scores were then used as continuous covariates in a
      Cox proportional hazards model to determine the adjusted impact of adjuvant
      radiation therapy on both local recurrence and the combined endpoint of use of
      salvage therapy and death due to progressive meningioma. RESULTS: The median
      follow-up in patients without recurrent disease was 4.9 years. After adjustment
      for pertinent confounding variables, radiation therapy was associated with
      decreased local recurrence in those undergoing gross total resection (hazard
      ratio, 0.25; 95% CI, 0.07-0.96; P = .04). No differences in overall survival were
      seen in patients who did and did not receive radiation therapy. CONCLUSION:
      Patients who have had a gross total resection of an atypical meningioma should be
      considered for adjuvant radiation therapy given the improvement in local control.
      Multicenter, prospective trials are required to definitively evaluate the
      potential impact of radiation therapy on survival in patients with atypical
      meningioma.

PMID- 24891454
TI  - Preliminary in vivo evaluation of a novel intrasaccular cerebral aneurysm
      occlusion device.
AB  - OBJECTIVE: Current endovascular technology does not offer a perfect solution for
      all cerebral aneurysms. Our group has built two versions of a novel aneurysm
      intrasaccular occlusion device (AIOD) to address the drawbacks associated with
      current occlusion devices. The objective of the present study was to perform
      pilot proof of concept in vivo testing of this new AIOD in swine and canines.
      METHODS: Two configurations of the AIOD, termed 'coil-in-shell' and 'gel-in
      shell', were implanted in surgically created sidewall aneurysms (n=4) in swine
      for acute occlusion studies, as well as sidewall (n=8) and bifurcation aneurysms
      (n=3) in canines to assess long term occlusion efficacy. Occlusion at all time
      points (immediate, 6 weeks, and 12 weeks) was evaluated by angiography.
      Neointimal healing at 12 weeks post-implantation in canines was examined
      histologically. RESULTS: Angiographic analysis showed that both the coil-in-shell
      and gel-in-shell devices achieved complete aneurysm occlusion immediately
      following device delivery in sidewall aneurysms in swine. In longer term canine
      studies, initial occlusion ranged from 71.3% to 100%, which was stable with no
      recurrence in any of the sidewall aneurysms at 6 or 12 weeks. Histological
      analysis at 12 weeks showed mature fibromuscular tissue at the neck of all
      aneurysms and no significant inflammatory response. CONCLUSIONS: The AIOD tested
      in this study showed promise in terms of acute and chronic occlusion of
      aneurysms. Our findings suggest that these devices have the potential to promote
      robust tissue healing at the aneurysm neck, which may minimize aneurysm
      recurrence. Although proof of principle has been shown, further work is needed to
      deliver this device through an endovascular route.

PMID- 24891455
TI  - VGLL1 expression is associated with a triple-negative basal-like phenotype in
      breast cancer.
AB  - Vestigial-like 1 (VGLL1) is a poorly characterized gene encoding a
      transcriptional co-activator structurally homologous to TAZ and YAP that
      modulates the Hippo pathway in Drosophila. In this study, we examined the
      expression of VGLL1 and its intronic miRNA, miR-934, in breast cancer. VGLL1 and
      miR-934 expression miRNA profiling was carried out on frozen samples of grade 3
      invasive ductal carcinomas. VGLL1 protein was also examined in 433 sporadic and
      BRCA1-associated breast carcinomas on tissue microarrays. RNA-seq data from The
      Cancer Genome Atlas (TCGA) was used to confirm differences in VGLL1 and miR-934
      expression in different breast cancer subtypes, and to correlate their expression
      with that of other genes and miRNAs. Of 28 miRNAs differentially expressed in
      estrogen receptor (ER)-positive and ER-negative grade 3 breast carcinomas, miR
      934 was most strongly upregulated in ER-negative carcinomas, and its expression
      was correlated with that of VGLL1. Nuclear VGLL1 expression was observed in 13%
      of sporadic breast carcinomas, and while VGLL1 was only occasionally found in
      luminal A (0.70%) and B (5.60%) carcinomas, it was often expressed in HER2
      positive (17%), triple-negative (TN) breast carcinomas (>40%) and BRCA1
      associated TN carcinomas (>50%). These findings were confirmed in the TCGA
      dataset, which revealed positive associations with luminal progenitor genes
      (GABRP, SLC6A14, FOXC1, PROM1, and BBOX1) and strong negative correlations with
      ER-associated genes (ESR1, C6ORF211, GATA3, and FOXA1). Moreover, VGLL1
      expression was associated with reduced overall survival. In conclusion, VGLL1 and
      miR-934 are mainly expressed in sporadic and BRCA1-associated TN basal-like
      breast carcinomas, and their coordinated expression, at least partially mediated
      by the direct modulation of ESR1, might be involved in the maintenance of a
      luminal progenitor phenotype.

PMID- 24891456
TI  - Characterization of the mTOR pathway in human normal adrenal and adrenocortical
      tumors.
AB  - The mTOR pathway has recently been suggested as a new potential target for
      therapy in adrenocortical carcinomas (ACCs). The aim of the current study is to
      describe the expression of the mTOR pathway in normal adrenals (NAs) and
      pathological adrenals and to explore whether there are correlation between the
      expression of these proteins and the in vitro response to sirolimus. For this
      purpose, the MTOR, S6K1 (RPS6KB1), and 4EBP1 (EIF4EBP1) mRNA expression were
      evaluated in ten NAs, ten adrenal hyperplasias (AHs), 17 adrenocortical adenomas
      (ACAs), and 17 ACCs by qPCR, whereas total(t)/phospho(p)-MTOR, t/p-S6K, and t/p
      4EBP1 protein expression were assessed in three NAs, three AHs, six ACAs, and 20
      ACCs by immunohistochemistry. The effects of sirolimus on cell survival and/or
      cortisol secretion in 12 human primary cultures of adrenocortical tumors (ATs)
      were also evaluated. In NAs and AHs, layer-specific expression of evaluated
      proteins was observed. S6K1 mRNA levels were lower in ACCs compared with NAs,
      AHs, and ACAs (P<0.01). A subset of ATs presented a moderate to high staining of
      the evaluated proteins. Median t-S6K1 protein expression in ACCs was lower than
      that in ACAs (P<0.01). Moderate to high staining of p-S6K1 and/or p-4EBP1 was
      observed in most ATs. A subset of ACCs not having moderate to high staining had a
      higher Weiss score than others (P<0.029). In primary AT cultures, sirolimus
      significantly reduced cell survival or cortisol secretion only in sporadic cases.
      In conclusion, these data suggest the presence of an activated mTOR pathway in a
      subset of ATs and a possible response to sirolimus only in certain ACC cases.

PMID- 24891457
TI  - Histone H2B monoubiquitination: roles to play in human malignancy.
AB  - Ubiquitination has traditionally been viewed in the context of polyubiquitination
      that is essential for marking proteins for degradation via the proteasome. Recent
      discoveries have shed light on key cellular roles for monoubiquitination,
      including as a post-translational modification (PTM) of histones such as histone
      H2B. Monoubiquitination plays a significant role as one of the largest histone
      PTMs, alongside smaller, better-studied modifications such as methylation,
      acetylation and phosphorylation. Monoubiquitination of histone H2B at lysine 120
      (H2Bub1) has been shown to have key roles in transcription, the DNA damage
      response and stem cell differentiation. The H2Bub1 enzymatic cascade involves E3
      RING finger ubiquitin ligases, with the main E3 generally accepted to be the
      RNF20-RNF40 complex, and deubiquitinases including ubiquitin-specific protease 7
      (USP7), USP22 and USP44. H2Bub1 has been shown to physically disrupt chromatin
      strands, fostering a more open chromatin structure accessible to transcription
      factors and DNA repair proteins. It also acts as a recruiting signal, actively
      attracting proteins with roles in transcription and DNA damage. H2Bub1 also
      appears to play central roles in histone cross-talk, influencing methylation
      events on histone H3, including H3K4 and H3K79. Most significantly, global levels
      of H2Bub1 are low to absent in advanced cancers including breast, colorectal,
      lung and parathyroid, marking H2Bub1 and the enzymes that regulate it as key
      molecules of interest as possible new therapeutic targets for the treatment of
      cancer. This review offers an overview of current knowledge regarding H2Bub1 and
      highlights links between dysregulation of H2Bub1-associated enzymes, stem cells
      and malignancy. 

PMID- 24891458
TI  - Equity impact of European individual-level smoking cessation interventions to
      reduce smoking in adults: a systematic review.
AB  - BACKGROUND: Smoking is the leading cause of health inequalities in Europe. Adults
      from lower socioeconomic status (SES) groups are more likely to smoke and less
      likely to quit than adults from higher SES groups. Smoking cessation support is
      an important element of tobacco control; however, the equity impact of individual
      level cessation support is uncertain. METHODS: Systematic review of individual
      level smoking cessation interventions delivered in European countries, reporting
      a smoking cessation outcome (quit) in adults of lower compared with higher SES.
      Equity impact was assessed as positive (reduced inequality), neutral (no
      difference by SES), negative (increased inequality) or unclear. RESULTS: Twenty
      nine studies were included using different types of support: behavioural and
      pharmacological (17); behavioural only (11), including specialist (5), brief
      advice (1), mass media (2), text-based (1) and Internet-based (2); and
      pharmacological only (1). The distribution of equity effects on quitting was 10
      neutral, 18 negative and 1 unclear. Two national studies of UK National Health
      Service (NHS) stop-smoking services showed overall positive equity impact on
      smoking prevalence. The evidence suggests that UK NHS services that target low
      SES smokers achieve a relatively higher service uptake among low-SES smokers,
      which can compensate for their lower quit rates. CONCLUSIONS: Untargeted smoking
      cessation interventions in Europe may have contributed to reducing adult smoking
      but are, on balance, likely to have increased inequalities in smoking. However,
      UK NHS stop-smoking services appear to reduce inequalities in smoking through
      increased relative reach through targeting services to low-SES smokers. More
      research is needed to strengthen the evidence-base for reducing smoking
      inequalities.

PMID- 24891459
TI  - Adolescent ecstasy use and depression: cause and effect, or two outcomes of home
      environment?
AB  - BACKGROUND: This study assessed the association between adolescent ecstasy use
      and depressive symptoms in adolescence. METHODS: The Belfast Youth Development
      Study surveyed a cohort annually from age 11 to 16 years. Gender, Strengths and
      Difficulties Questionnaire emotional subscale, living arrangements, parental
      affluence, parent and peer attachment, tobacco, alcohol, cannabis and ecstasy use
      were investigated as predictors of Short Mood and Feelings Questionnaire (SMFQ)
      outcome. RESULTS: Of 5371 respondents, 301 (5.6%) had an SMFQ > 15, and 1620
      (30.2) had missing data for SMFQ. Around 8% of the cohort had used ecstasy by the
      end of follow-up. Of the non-drug users, ~2% showed symptoms of depression,
      compared with 6% of those who had used alcohol, 6% of cannabis users, 6% of
      ecstasy users and 7% of frequent ecstasy users. Without adjustment, ecstasy users
      showed around a 4-fold increased odds of depressive symptoms compared with non
      drug users [odds ratio (OR) = 0.26; 95% confidence interval (CI) = 0.10, 0.68].
      Further adjustment for living arrangements, peer and parental attachment
      attenuated the association to under a 3-fold increase (OR = 0.37; 95% CI = 0.15,
      0.94). There were no differences by frequency of use. CONCLUSIONS: Ecstasy use
      during adolescence may be associated with poorer mental health; however, this
      association can be explained by the confounding social influence of family
      dynamics. These findings could be used to aid effective evidence-based drug
      policies, which concentrate criminal justice and public health resources on
      reducing harm.

PMID- 24891460
TI  - Implementation of malaria dynamic models in municipality level early warning
      systems in Colombia. Part I: description of study sites.
AB  - As part of the Integrated National Adaptation Pilot project and the Integrated
      Surveillance and Control System, the Colombian National Institute of Health is
      working on the design and implementation of a Malaria Early Warning System
      framework, supported by seasonal climate forecasting capabilities, weather and
      environmental monitoring, and malaria statistical and dynamic models. In this
      report, we provide an overview of the local ecoepidemiologic settings where four
      malaria process-based mathematical models are currently being implemented at a
      municipal level. The description includes general characteristics, malaria
      situation (predominant type of infection, malaria-positive cases data, malaria
      incidence, and seasonality), entomologic conditions (primary and secondary
      vectors, mosquito densities, and feeding frequencies), climatic conditions
      (climatology and long-term trends), key drivers of epidemic outbreaks, and non
      climatic factors (populations at risk, control campaigns, and socioeconomic
      conditions). Selected pilot sites exhibit different ecoepidemiologic settings
      that must be taken into account in the development of the integrated surveillance
      and control system. 

PMID- 24891461
TI  - Awareness of meningococcal disease among travelers from the United Kingdom to the
      meningitis belt in Africa.
AB  - Meningococcal disease causes considerable morbidity and has a high case-fatality
      rate. In the United Kingdom, the meningococcal quadrivalent vaccine is
      recommended for travelers visiting the meningitis belt of Africa. We analyzed 302
      responses to a cross-sectional study conducted in 2010 of travelers who had
      visited the meningitis belt recently or were shortly due to travel there. Using
      the results of an online questionnaire, we assessed knowledge and understanding
      of meningococcal disease and likelihood of uptake of meningococcal immunization
      before travel. Meningococcal vaccine uptake was 30.1%. Although global scores in
      the questionnaire did not correlate with vaccine uptake, knowledge of the
      meningitis belt and knowledge of certain key symptoms or signs were statistically
      associated with high vaccine uptake. We conclude that improved education of
      travelers may improve vaccine uptake before travel to the meningitis belt in
      Africa. 

PMID- 24891462
TI  - Myocarditis in a traveler returning from the Dominican Republic: an unusual
      presentation of dengue fever.
AB  - Myocarditis is an uncommon manifestation of dengue fever. We describe a case of a
      69-year-old Hispanic male who presented to an emergency room in New York City 3
      days after returning from a trip to the Dominican Republic complaining of a 1-day
      history of chest pain and fever. His first electrocardiogram showed a new left
      bundle branch block, and initial cardiac enzymes included troponin of 5 ng/dL,
      creatine kinase-MB of 9 ng/mL, and myoglobin of 234 ng/mL. Dengue fever
      antibodies were found to be elevated: immunoglobulin M (IgM) titer was 2.48
      (reference range < 0.9), and immunoglobulin G (IgG) titer was 4.26 (reference
      range < 0.9). The patient was diagnosed with myocarditis caused by dengue fever.
      He improved after 1 week with conservative management in a telemetry unit and was
      discharged home. 

PMID- 24891463
TI  - Viral hemorrhagic fever cases in the country of Georgia: Acute Febrile Illness
      Surveillance Study results.
AB  - Minimal information is available on the incidence of Crimean-Congo hemorrhagic
      fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537
      patients with fever >= 38 degrees C for >= 48 hours without a diagnosis were
      enrolled into a sentinel surveillance study to investigate the incidence of nine
      pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic
      fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM)
      antibodies. Two of the patients enrolled in the study had acute renal failure.
      These 2 of 537 enrolled patients were the only patients in the study positive for
      hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus
      are contributing causes of acute febrile syndromes of infectious origin in
      Georgia. These findings support introduction of critical diagnostic approaches
      and confirm the need for additional surveillance in Georgia. 

PMID- 24891464
TI  - Sequential episodes of dengue--Puerto Rico, 2005-2010.
AB  - Of 53,633 suspected dengue cases reported to a passive dengue surveillance system
      in Puerto Rico during 2005-2010, 949 individuals were reported on more than one
      occasion and 21 had laboratory-confirmed dengue on two separate occasions. Median
      time between illness episodes was 2.9 years (range: 62 days-5.3 years). Seventeen
      (81%) individuals with sequential episodes of dengue were male, and seven (33%)
      were adults. All 21 individuals experienced one episode and seven (33%)
      individuals experienced both episodes during a large epidemic that occurred in
      2010. These observations show that heterotypic dengue virus immunity that
      protects against illness may have considerable variability but typically does not
      last longer than 3 years. 

PMID- 24891465
TI  - Glucose-6-phosphate dehydrogenase deficiency A- variant in febrile patients in
      Haiti.
AB  - Haiti is one of two remaining malaria-endemic countries in the Caribbean. To
      decrease malaria transmission in Haiti, primaquine was recently added to the
      malaria treatment public health policy. One limitation of primaquine is that, at
      certain doses, primaquine can cause hemolytic anemia in individuals with glucose
      6-phosphate dehydrogenase (G6PD) deficiency (G6PDd). In this study, we genotyped
      two mutations (A376G and G202A), which confer the most common G6PDd variant in
      West African populations, G6PDd A-. We estimated the frequency of G6PDd A- in a
      sample of febrile patients enrolled in an on-going malaria study who represent a
      potential target population for a primaquine mass drug administration. We found
      that 33 of 168 individuals carried the G6PDd A- allele (includes A- hemizygous
      males, A- homozygous or heterozygous females) and could experience toxicity if
      treated with primaquine. These data inform discussions on safe and effective
      primaquine dosing and future malaria elimination strategies for Haiti. 

PMID- 24891467
TI  - The impact of the Fogarty International Clinical Scholars and Fellows program
      extends beyond borders.

PMID- 24891466
TI  - Preliminary investigation of the contribution of CYP2A6, CYP2B6, and UGT1A9
      polymorphisms on artesunate-mefloquine treatment response in Burmese patients
      with Plasmodium falciparum malaria.
AB  - CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a
      three-day course of artesunate-mefloquine was investigated in 71 Burmese patients
      with uncomplicated Plasmodium falciparum malaria. Results provide evidence for
      the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma
      concentrations of artesunate/dihydroartemisinin and treatment response. In one
      patient who had the CYP2A6*1A/*4C genotype (decreased enzyme activity), plasma
      concentration of artesunate at one hour appeared to be higher, and the
      concentration of dihydroartemisinin was lower than for those carrying other
      genotypes (415 versus 320 ng/mL). The proportion of patients with adequate
      clinical and parasitologic response who had the CYP2B6*9/*9 genotype (mutant
      genotype) was significantly lower compared with those with late parasitologic
      failure (14.0% versus 19.0%). Confirmation through a larger study in various
      malaria-endemic areas is required before a definite conclusion on the role of
      genetic polymorphisms of these drug-metabolizing enzymes on treatment response
      after artesunate-based combination therapy can be made. 

PMID- 24891468
TI  - Fatal melioidosis in goats in Bangkok, Thailand.
AB  - Bangkok, Thailand, is a city considered to be at low risk for melioidosis. We
      describe 10 goats that died of melioidosis in Bangkok. Half of them were born and
      reared in the city. Multilocus sequence typing ruled out an outbreak. This
      finding challenges the assumption that melioidosis is rarely acquired in central
      Thailand. 

PMID- 24891469
TI  - Placental malaria is rare among Zanzibari pregnant women who did not receive
      intermittent preventive treatment in pregnancy.
AB  - Zanzibar has transitioned from malaria control to the pre-elimination phase, and
      the continued need for intermittent preventive treatment during pregnancy (IPTp)
      has been questioned. We conducted a prospective observational study to estimate
      placental malaria positivity rate among women who did not receive IPTp with
      sulfadoxine-pyrimethamine. A convenience sample of pregnant women was enrolled
      from six clinics on the day of delivery from August of 2011 to September of 2012.
      Dried placental blood spot specimens were analyzed by polymerase chain reaction
      (PCR); 9 of 1,349 specimens (0.7%; precision estimate = 0.2-1.1%) were PCR
      positive for Plasmodium falciparum. Placental infection was detected on both
      Pemba (N = 3) and Unguja (N = 6). Placental malaria positivity in Zanzibar was
      low, even in the absence of IPTp. It may be reasonable for the Ministry of Health
      to consider discontinuing IPTp, intensifying surveillance efforts, and promoting
      insecticide-treated nets and effective case management of malaria in pregnancy. 

PMID- 24891470
TI  - Trypanosoma cruzi meningoencephalitis in a patient with acquired immunodeficiency
      syndrome.
AB  - As a result of global migration, a significant number of people with Trypanosoma
      cruzi infection now live in the United States, Canada, many countries in Europe,
      and other non-endemic countries. Trypanosoma cruzi meningoencephalitis is a rare
      cause of ring-enhancing lesions in patients with acquired immunodeficiency
      syndrome (AIDS) that can closely mimic central nervous system (CNS)
      toxoplasmosis. We report a case of CNS Chagas reactivation in an AIDS patient
      successfully treated with benznidazole and antiretroviral therapy in the United
      States. 

PMID- 24891471
TI  - Zoonotic Ancylostoma ceylanicum infection detected by endoscopy.
AB  - We report a case of Ancylostoma ceylanicum infection detected by endoscopy. It
      was diagnosed and confirmed using polymerase chain reaction (PCR) and DNA
      sequencing. The patient is a 58-year-old Malaysian woman who lives in a rural
      area, where uncontrolled populations of stray and semidomesticated dogs live in
      close proximity with humans. 

PMID- 24891472
TI  - A review of the use of the 5 A's model for weight loss counselling: differences
      between physician practice and patient demand.
AB  - BACKGROUND: The 5 A's (Assess, Advise, Agree, Assist and Arrange) is a model that
      can be used by primary care physicians and practitioners to promote patient
      behaviour change. The 5 A's model is a viable intervention for encouraging weight
      management in response to the epidemic of obesity among patients. AIM: To
      identify and summarize quantitative research related to the 5 A's patients want
      to receive from their physicians during weight loss discussions and how
      frequently physicians use each practice. DESIGN AND SETTING: We conducted a
      systematic literature review of the MEDLINE/PubMed database using relevant
      keywords. Of 230 articles originally identified, 15 articles included
      quantitative research data from cross-sectional studies related to the aim of
      this review. RESULTS: Based on the available evidence, the majority of patients
      want to discuss weight loss with their physicians, with the Assist and Arrange
      aspects of the 5 A's being most desired. However, physicians most frequently
      Advise and Assess, and rarely Agree, Assist or Arrange. CONCLUSIONS: There are
      some significant limitations to the available evidence, including a limited
      number of studies addressing patient preference, inconsistent assessment of all
      aspects of the 5 A's, a lack of longitudinal designs and failure to take
      contextual factors such as patient and physician characteristics into account
      when interpreting study results. Future studies should address these limitations,
      document the outcomes that result from better physician training in lifestyle
      modification strategies and determine how to best routinely implement all aspects
      of the 5 A's for weight management in family practice settings.

PMID- 24891473
TI  - Biochemical markers of neurodegeneration in hereditary diffuse
      leucoencephalopathy with spheroids.
AB  - Hereditary diffuse leucoencephalopathy with spheroids (HDLS) is a rare autosomal
      dominantly inherited disease with unknown pathophysiology. Diagnosis of
      neurodegenerative diseases is increasingly based on biomarkers. Although lumbar
      puncture is routinely performed during the diagnostic workup of HDLS, reports on
      alterations of neurodegeneration-specific biochemical markers have not been
      documented so far. We report a 35-year-old woman with clinical, radiological and
      neuropathological signs of HDLS. She suffered from a rapidly progressive frontal
      lobe syndrome. Brain MRI revealed diffuse leucoencephalopathy with predominant
      involvement of the periventricular white matter and corpus callosum. Although she
      was severely impaired and leucoencephalopathy was prominent, only cerebrospinal
      fluid total-tau was moderately elevated. Other markers of neuronal (NSE) and
      astrocytic (S100B) damage were within normal range. Therefore, biochemical
      markers of central nervous system damage are not helpful in the diagnosis of
      HDLS. 

PMID- 24891474
TI  - Rapidly progressive aortic aneurysmal dilation in a child with systemic lupus
      erythematosus: too early too severe.
AB  - About 10-20% of systemic lupus erythematosus cases occur in children, often with
      more severe features at onset and more active disease over time compared with
      adults. Cardiovascular complications are common in this population but thoracic
      aortic aneurysms rarely occur. Although the pathophysiology of this complication
      remains unclear, vasculitis seems to play an important role, leading to
      degeneration and fibrosis of the media and formation of the aneurysm. We report
      the case of a 9-year-old systemic lupus erythematosus patient with important
      renal involvement, who underwent aortic replacement surgery for the treatment of
      an aortic aneurysm. This case highlights the importance of monitoring the
      thoracic aorta in children with systemic lupus erythematosus and the need for the
      development of appropriate early management strategies for this serious
      complication. 

PMID- 24891475
TI  - Large air-fluid level in the perinephric space without obstruction.

PMID- 24891476
TI  - Intraneural ganglion cyst on the external popliteal nerve.
AB  - There are many causes for the paralysis of the external sciatic popliteal nerve ,
      such as the intraneural ganglion cyst. In this case, we evaluate a 52-year-old
      woman with no relevant personal record, who was admitted with paresis of the
      right foot of 4 months of evolution associated with alterations in the
      sensitivity that rose up to the posterolateral region of the leg. The diagnosis
      was based on MR and cyst decompression and disconnection of the articular branch.
      Given the low incidence of these lesions, their origin is still subject to
      controversy. The most widely accepted theory is the unifying articular theory
      described by Spinner in the year 2003. Intraneural ganglion cysts must be
      included in the differential diagnosis of progressive paralysis of the sciatic
      nerve, lesions of the nerve root at L5 and nerve sheath tumours that start at the
      lateral compartment of the knee. The treatment of a fibular intraneural ganglion
      cyst must be surgical and the operation must be performed as soon as possible.

PMID- 24891478
TI  - Glove and PICO: a novel technique for treatment of chronic wound due to
      osteomyelitis of the hand.
AB  - Chronic wounds on the dorsum of the hand are often challenging to treat. Vacuum
      assisted closure has enjoyed widespread use in recent years for many difficult
      chronic wounds as an alternative to surgery. Unfortunately, owing to the unique
      anatomy of the hand, it is usually very difficult to get a seal without
      significantly immobilising the hand. We report a case of a chronic wound on the
      dorsum of the hand as a result of osteomyelitis in a 37-year-old man, which was
      treated with Single Use Negative Pressure Wound Therapy, 'PICO' (Smith and Nephew
      Co, UK). We combined the PICO dressing with a rubber glove to get a good seal
      enabling appropriate suction without immobilising the hand. Once the wound bed
      was ready, the defect was covered with a reverse forearm flap. 

PMID- 24891477
TI  - Intravenous iron administration together with parenteral nutrition to very
      preterm Jehovah's Witness twins.
AB  - Preterm twin sisters (monozygotic) were born at gestational age 27 weeks and 5
      days with birth weights of 935 and 735 g. They were admitted to our neonatal
      intensive care unit for a period of 1 month. Their parents were Jehovah's
      Witnesses and refused blood transfusion for their preterm daughters. Subcutaneous
      erythropoietin and intravenous iron were given as a prophylactic to avoid
      anaemia.

PMID- 24891479
TI  - Pituitary apoplexy in a patient with suspected metastatic bronchogenic carcinoma.

PMID- 24891480
TI  - The importance of "His" story.
AB  - A 73-year-old previously healthy man presented with a 3-day history of rigours,
      abdominal pain, diarrhoea, haemoptysis and myalgia. He had not been abroad
      recently, but reported being a farmer and having had a recent rat infestation.
      Laboratory investigations revealed acute kidney failure, deranged liver function
      tests, raised C reactive protein and a chest CT revealed bilateral ground-glass
      opacities. This presentation was consistent with icteric leptospirosis which was
      confirmed by serological testing. Following haemofiltration and the
      administration of antibiotics the patient made an excellent recovery from his
      leptospirosis. 

PMID- 24891481
TI  - Dural arteriovenous fistula presenting with progressive dementia and
      parkinsonism.
AB  - We report a rare case of progressive parkinsonism and cognitive dysfunction due
      to dural arteriovenous fistula (DAVF). A 69-year-old man, with a history of
      hypertension and diabetes, was admitted to our hospital because of parkinsonism
      and dementia. Susceptibility-weighted imaging (SWI) revealed a thrombus in the
      superior sagittal sinus (SSS) and marked dilation of the medullary vein
      suggestive of the presence of comorbid DAVF. A single-photon emission CT (SPECT)
      showed widespread hypoperfusion in the bilateral frontal lobes. Selective
      cerebral angiography revealed a DAVF in SSS. These symptoms were significantly
      ameliorated following transvenous embolisation of the venous sinus at the
      shunting point. Reversible parkinsonism and dementia after embolisation was
      correlated with decreased dilation of medullary vein on SWI and improved cerebral
      blood flow on SPECT in the frontal lobes. Differentiation of parkinsonian and
      dementia symptoms due to DAVF from those associated with neurodegenerative
      disease is of great importance because DAVF-associated deficits may be reversed
      by endovascular therapy. 

PMID- 24891482
TI  - Complete rupture of the pancreas after a kick into the abdomen during a football
      match.
AB  - Pancreatic injury is uncommon, accounting for less than 7% of penetrating and 5%
      of blunt abdominal trauma. Blunt isolated pancreatic trauma in football has been
      rarely described in the literature and its diagnosis, detection and treatment
      still remains a challenge. We report a case of a young adult with an isolated
      complete rupture of the pancreatic body due to a blunt abdominal trauma during a
      football game. In order to preserve the pancreas and therefore retain function,
      we performed a terminolateral pancreaticojejunostomy. The postoperative course of
      the patient was uneventful. The diagnosis of isolated injuries of the pancreas in
      blunt abdominal trauma can be difficult and challenging and due to the nature of
      the game physicians should be highly alerted when dealing with football players
      sustaining abdominal trauma. 

PMID- 24891483
TI  - Misinterpreting risk and test results delays diagnosis in a patient with
      pulmonary embolism.
AB  - We report the case of a middle-aged man where a diagnosis of pulmonary embolism
      (PE) was delayed due to initial underestimation of risk and over-reliance on D
      dimer testing. The patient presented with pleuritic chest pain after a 5 h
      domestic flight. The treating clinicians presumed that this duration of
      immobilisation was insufficient to cause a PE, D-dimer was not measured and the
      patient was discharged home. One week later, the patient re-presented due to
      persistence of chest pain. On this occasion, D-dimer was measured and it was
      normal, which was interpreted as excluding a PE. Subsequently, a CT pulmonary
      angiogram was performed, which demonstrated a subsegmental PE. This case
      highlights the importance of accurate assessment of PE-risk factors and following
      clinical guidelines, since a delayed diagnosis of PE is associated with increased
      mortality. 

PMID- 24891484
TI  - Hunting mimics and chameleons: diagnostic difficulties in atypical acute
      ischaemic stroke.
AB  - The seemingly straightforward diagnosis of acute ischaemic stroke can be
      complicated by the presence of conditions presenting similarly to stroke, and
      atypical strokes presenting with confusing and non-classical signs. We present a
      diagnostic quest to disentangle the effects of a number of stroke mimics from
      those of an underlying bilateral cerebrovascular phenomena, where with
      appropriate treatment of the non-stroke conditions the patient was able to make a
      near complete neurological recovery. 

PMID- 24891485
TI  - Prosthetic rehabilitation of palatal perforation in a patient with 'syphilis: the
      great imitator'.
AB  - Syphilis is a sexually transmissible disease caused by treponema palladium, a
      microaerophilic spirochete. Syphilis may progress from primary to tertiary stage
      if left unnoticed and untreated. Dentists should be vigilant and suspect sexually
      transmitted infections such as syphilis in the differential diagnosis of oral
      inflammatory or ulcerative lesions with palatal perforation. Moreover, it is
      imperative that dentists should have knowledge about its stages, characteristic
      features, oral presentation and prosthetic rehabilitation. This case report
      describes a case of tertiary syphilis with palatal perforation and the prosthetic
      rehabilitation of the defect with a prosthetic obturator. 

PMID- 24891486
TI  - A rare manifestation of neonatal alloimmune thrombocytopaenia.
AB  - Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal
      incompatibility with maternal sensitisation against a fetal human platelet
      antigen (HPA) and antibodies transfer to the fetal circulation, leading to
      platelet destruction. The clinical presentation is variable and isolated
      intraocular haemorrhage is rare. We present the case of a male newborn, with
      intrauterine growth restriction, born at 29 weeks due to pre-eclampsia. He
      presented proptosis of the left eye, hyphaema and elevated intraocular pressure,
      with no other signs of haemorrhage. Severe thrombocytopaenia was found
      (27*10(9)/L). Perinatal infection and maternal thrombocytopaenia were excluded.
      Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were
      found in the mother. Platelet crossmatch between the father's platelets and
      mother's plasma was positive. Platelet transfusions and intravenous
      immunoglobulin were given with favourable response. This case highlights an
      unusual presentation of NAIT, which should be suspected in the presence of severe
      thrombocytopaenia in the first 24-72 h of life. 

PMID- 24891487
TI  - Limbic encephalitis.
AB  - We present a case of paraneoplastic limbic encephalitis, describing the
      presenting features, diagnosis and management plan. Limbic encephalitis is one
      differential of rapidly progressive dementia. We describe a rational approach to
      the diagnosis of the patient with rapid cognitive decline. 

PMID- 24891488
TI  - Dyke-Davidoff-Masson syndrome: a clinicoradiological amalgam.
AB  - Dyke-Davidoff-Masson syndrome is a relatively rare syndrome with its typical
      clinical and radiological features including facial asymmetry, hemiplegia,
      cerebral hemiatrophy, mental retardation with calvarial thickening, hypertrophy
      of sinuses and elevated petrous ridge on imaging. We present here a case of
      congenital type Dyke-Davidoff-Masson syndrome with some additional features in
      the form of microcephaly, hypospadias and pachygyria. 

PMID- 24891489
TI  - Averting a crisis by 'add'ing up the clues.

PMID- 24891490
TI  - Unilateral Warthin's tumour in a patient of Afro-Caribbean descent.
AB  - Warthin's tumours are the second most common benign tumours of the parotid gland.
      The authors report the case of a 40-year-old man of Afro-Caribbean decent who
      presented with a painless mass at the angle of the right mandible. It was an
      incidental finding while shaving and was not associated with any symptoms.
      Arrangements were made for him to undergo an ear, nose and throat (ENT)
      evaluation. Axial contrast-enhanced CT of head and neck region revealed a well
      defined cystic lesion. Fine-needle aspiration cytology was inconclusive. Right
      superficial partial parotidectomy was performed to remove the lesion.
      Histological examination confirmed a diagnosis of a Warthin's tumour. 

PMID- 24891491
TI  - Thrombocytopaenia with absent radius (not radii).

PMID- 24891492
TI  - Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy.
AB  - Ruxolitinib is a novel inhibitor of the Janus kinase (JAK) pathway that has
      become available for the treatment of myelofibrosis. There are increasing reports
      of opportunistic infections associated with ruxolitinib therapy. We present a
      case of Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy.
      Clinicians should consider the use of pneumocystis prophylaxis when using
      ruxolitinib. 

PMID- 24891493
TI  - Stereovision and augmented reality for closed-loop control of grasping in hand
      prostheses.
AB  - OBJECTIVE: Technologically advanced assistive devices are nowadays available to
      restore grasping, but effective and effortless control integrating both feed
      forward (commands) and feedback (sensory information) is still missing. The goal
      of this work was to develop a user friendly interface for the semi-automatic and
      closed-loop control of grasping and to test its feasibility. APPROACH: We
      developed a controller based on stereovision to automatically select grasp type
      and size and augmented reality (AR) to provide artificial proprioceptive
      feedback. The system was experimentally tested in healthy subjects using a
      dexterous hand prosthesis to grasp a set of daily objects. The subjects wore AR
      glasses with an integrated stereo-camera pair, and triggered the system via a
      simple myoelectric interface. MAIN RESULTS: The results demonstrated that the
      subjects got easily acquainted with the semi-autonomous control. The stereovision
      grasp decoder successfully estimated the grasp type and size in realistic,
      cluttered environments. When allowed (forced) to correct the automatic system
      decisions, the subjects successfully utilized the AR feedback and achieved close
      to ideal system performance. SIGNIFICANCE: The new method implements a high
      level, low effort control of complex functions in addition to the low level
      closed-loop control. The latter is achieved by providing rich visual feedback,
      which is integrated into the real life environment. The proposed system is an
      effective interface applicable with small alterations for many advanced
      prosthetic and orthotic/therapeutic rehabilitation devices.

PMID- 24891495
TI  - A delayed diagnosis of Mounier-Kuhn syndrome.
AB  - Following a provisional diagnosis of asthma of several years' duration by his
      general practitioner, a 43-year-old otherwise healthy man who was a non-smoker
      was referred to a pulmonologist with worsening productive cough and exertional
      breathlessness. A thoracic CT scan revealed dilated airways (tracheal diameter 35
      mm, left bronchial diameter 20 mm, right bronchial diameter 18 mm). Inflamed and
      easily collapsible airways were seen on bronchoscopy. The patient remained stable
      and was followed up with regular spirometry. A follow-up CT scan 7 years later
      showed tracheobronchomegaly (tracheal diameter 42 mm, left bronchial diameter 25
      mm, right bronchial diameter 23 mm) with large cystic spaces consistent with
      Mounier-Kuhn syndrome. Repeat bronchoscopy showed a massively dilated trachea and
      generalised collapse on expiration with a dilated thin-walled bronchial tree. He
      was deemed ineligible for lung transplantation due to the extent of airway
      involvement making it difficult to anastomose donor lung to native tissue. 

PMID- 24891496
TI  - Neurally and ocularly informed graph-based models for searching 3D environments.
AB  - OBJECTIVE: As we move through an environment, we are constantly making
      assessments, judgments and decisions about the things we encounter. Some are
      acted upon immediately, but many more become mental notes or fleeting impressions
      our implicit 'labeling' of the world. In this paper, we use physiological
      correlates of this labeling to construct a hybrid brain-computer interface (hBCI)
      system for efficient navigation of a 3D environment. APPROACH: First, we record
      electroencephalographic (EEG), saccadic and pupillary data from subjects as they
      move through a small part of a 3D virtual city under free-viewing conditions.
      Using machine learning, we integrate the neural and ocular signals evoked by the
      objects they encounter to infer which ones are of subjective interest to them.
      These inferred labels are propagated through a large computer vision graph of
      objects in the city, using semi-supervised learning to identify other, unseen
      objects that are visually similar to the labeled ones. Finally, the system plots
      an efficient route to help the subjects visit the 'similar' objects it
      identifies. MAIN RESULTS: We show that by exploiting the subjects' implicit
      labeling to find objects of interest instead of exploring naively, the median
      search precision is increased from 25% to 97%, and the median subject need only
      travel 40% of the distance to see 84% of the objects of interest. We also find
      that the neural and ocular signals contribute in a complementary fashion to the
      classifiers' inference of subjects' implicit labeling. SIGNIFICANCE: In summary,
      we show that neural and ocular signals reflecting subjective assessment of
      objects in a 3D environment can be used to inform a graph-based learning model of
      that environment, resulting in an hBCI system that improves navigation and
      information delivery specific to the user's interests.

PMID- 24891497
TI  - Stochastic optimal control of single neuron spike trains.
AB  - OBJECTIVE: External control of spike times in single neurons can reveal important
      information about a neuron's sub-threshold dynamics that lead to spiking, and has
      the potential to improve brain-machine interfaces and neural prostheses. The goal
      of this paper is the design of optimal electrical stimulation of a neuron to
      achieve a target spike train under the physiological constraint to not damage
      tissue. APPROACH: We pose a stochastic optimal control problem to precisely
      specify the spike times in a leaky integrate-and-fire (LIF) model of a neuron
      with noise assumed to be of intrinsic or synaptic origin. In particular, we allow
      for the noise to be of arbitrary intensity. The optimal control problem is solved
      using dynamic programming when the controller has access to the voltage (closed
      loop control), and using a maximum principle for the transition density when the
      controller only has access to the spike times (open-loop control). MAIN RESULTS:
      We have developed a stochastic optimal control algorithm to obtain precise spike
      times. It is applicable in both the supra-threshold and sub-threshold regimes,
      under open-loop and closed-loop conditions and with an arbitrary noise intensity;
      the accuracy of control degrades with increasing intensity of the noise.
      Simulations show that our algorithms produce the desired results for the LIF
      model, but also for the case where the neuron dynamics are given by more complex
      models than the LIF model. This is illustrated explicitly using the Morris-Lecar
      spiking neuron model, for which an LIF approximation is first obtained from a
      spike sequence using a previously published method. We further show that a
      related control strategy based on the assumption that there is no noise performs
      poorly in comparison to our noise-based strategies. The algorithms are
      numerically intensive and may require efficiency refinements to achieve real-time
      control; in particular, the open-loop context is more numerically demanding than
      the closed-loop one. SIGNIFICANCE: Our main contribution is the online feedback
      control of a noisy neuron through modulation of the input, taking into account
      physiological constraints on the control. A precise and robust targeting of
      neural activity based on stochastic optimal control has great potential for
      regulating neural activity in e.g. prosthetic applications and to improve our
      understanding of the basic mechanisms by which neuronal firing patterns can be
      controlled in vivo.

PMID- 24891494
TI  - Neurite outgrowth on electrospun PLLA fibers is enhanced by exogenous electrical
      stimulation.
AB  - OBJECTIVE: Both electrical stimuli (endogenous and exogenous) and topographical
      cues are instructive to axonal extension. This report, for the first time,
      investigated the relative dominance of directional topographical guidance cues
      and directional electrical cues to enhance and/or direct primary neurite
      extension. We hypothesized the combination of electrical stimulation with
      electrospun fiber topography would induce longer neurite extension from dorsal
      root ganglia neurons than the presence of electrical stimulation or aligned
      topography alone. APPROACH: To test the hypothesis, neurite outgrowth was
      examined on laminin-coated poly-L-lactide films or electrospun fibers (2 um in
      diameter) in the presence or absence of electrical stimulation. Immunostained
      neurons were semi-automatically traced using Neurolucida software and morphology
      was evaluated. MAIN RESULTS: Neurite extension increased 74% on the aligned
      fibers compared to film controls. Stimulation alone increased outgrowth by 32% on
      films or fibers relative to unstimulated film controls. The co-presentation of
      topographical (fibers) with biophysical (electrical stimulation) cues resulted in
      a synergistic 126% increase in outgrowth relative to unstimulated film controls.
      Field polarity had no influence on the directionality of neurites, indicating
      topographical cues are responsible for guiding neurite extension. SIGNIFICANCE:
      Both cues (electrical stimulation and fiber geometry) are modular in nature and
      can be synergistically applied in conjunction with other common methods in
      regenerative medicine such as controlled release of growth factors to further
      influence axonal growth in vivo. The combined application of electrical and
      aligned fiber topographical guidance cues described herein, if translated in
      vivo, could provide a more supportive environment for directed and robust axonal
      regeneration following peripheral nerve injury.

PMID- 24891498
TI  - Closed-loop optical neural stimulation based on a 32-channel low-noise recording
      system with online spike sorting.
AB  - OBJECTIVE: Closed-loop operation of neuro-electronic systems is desirable for
      both scientific and clinical (neuroprosthesis) applications. Integrating optical
      stimulation with recording capability further enhances the selectivity of neural
      stimulation. We have developed a system enabling the local delivery of optical
      stimuli and the simultaneous electrical measuring of the neural activities in a
      closed-loop approach. APPROACH: The signal analysis is performed online through
      the implementation of a template matching algorithm. The system performance is
      demonstrated with the recorded data and in awake rats. MAIN RESULTS:
      Specifically, the neural activities are simultaneously recorded, detected,
      classified online (through spike sorting) from 32 channels, and used to trigger a
      light emitting diode light source using generated TTL signals. SIGNIFICANCE: A
      total processing time of 8 ms is achieved, suitable for optogenetic studies of
      brain mechanisms online.

PMID- 24891499
TI  - Conductance and Fano factor in normal/ferromagnetic/normal bilayer graphene
      junction.
AB  - We theoretically investigate the transport properties of bilayer graphene
      junctions, where the ferromagnetic strips are attached to the middle region of
      the graphene sheet. In these junctions, we can control the band gap and the band
      structure of the bilayer graphene by using the bias voltage between the layers
      and the exchange field induced on the layers. The conductance and Fano factor (F
      ) are calculated by the Landauer-Buttiker formula. It is found that when the
      voltage between the layers or the exchange field are tuned, the pseudodiffusive
      (F = 1/3) transport turns into tunneling (F = 1) or ballistic transport (F = 0).
      By tuning the potential difference between the layers, one can control the spin
      polarization of the current.

PMID- 24891500
TI  - Phase transformations of crystalline SiO2 versus dynamic disorder between room 
      temperature and liquid state.
AB  - The sequence of phase transitions of crystalline silica has been probed by
      infrared emission spectroscopy. The lattice dynamics, deeply impacted by the low
      frequency dynamic disorder, exhibit with increasing temperature signs of
      inhomogeneous broadening of the symmetry allowed normal modes. High frequency
      supplementary components are also activated. The analysis with a causal Voigt
      dielectric function model within the framework of hard mode spectroscopy allowed
      a fine characterization of solid-solid phase transitions. We also report
      experimental evidence showing that the occurrence of the intermediate ill-defined
      region above 1300 K is concomitant with the reactivation of the low frequency
      dynamic disorder; a behavior change that on the way explains the appearance of
      the negative thermal expansion regime.

PMID- 24891501
TI  - Identification of the glucosyltransferase that converts hydroxymethyluracil to
      base J in the trypanosomatid genome.
AB  - O-linked glucosylation of thymine in DNA (base J) is an important regulatory
      epigenetic mark in trypanosomatids. beta-d-glucopyranosyloxymethyluracil (base J)
      synthesis is initiated by the JBP1/2 enzymes that hydroxylate thymine, forming 5
      hydroxymethyluracil (hmU). hmU is then glucosylated by a previously unknown
      glucosyltransferase. A recent computational screen identified a possible
      candidate for the base J-associated glucosyltransferase (JGT) in trypanosomatid
      genomes. We demonstrate that recombinant JGT utilizes uridine diphosphoglucose to
      transfer glucose to hmU in the context of dsDNA. Mutation of conserved residues
      typically involved in glucosyltransferase catalysis impairs DNA glucosylation in
      vitro. The deletion of both alleles of JGT from the genome of Trypanosoma brucei
      generates a cell line that completely lacks base J. Reintroduction of JGT in the
      JGT KO restores J synthesis. Ablation of JGT mRNA levels by RNAi leads to the
      sequential reduction in base J and increased levels of hmU that dissipate
      rapidly. The analysis of JGT function confirms the two-step J synthesis model and
      demonstrates that JGT is the only glucosyltransferase enzyme required for the
      second step of the pathway. Similar to the activity of the related Ten-Eleven
      Translocation (TET) family of dioxygenases on 5mC, our studies also suggest the
      ability of the base J-binding protein enzymes to catalyze iterative oxidation of
      thymine in trypanosome DNA. Here we discuss the regulation of hmU and base J
      formation in the trypanosome genome by JGT and base J-binding protein. 

PMID- 24891502
TI  - The caspase-8 homolog Dredd cleaves Imd and Relish but is not inhibited by p35.
AB  - In Drosophila, the Imd pathway is activated by diaminopimelic acid-type
      peptidoglycan and triggers the humoral innate immune response, including the
      robust induction of antimicrobial peptide gene expression. Imd and Relish, two
      essential components of this pathway, are both endoproteolytically cleaved upon
      immune stimulation. Genetic analyses have shown that these cleavage events are
      dependent on the caspase-8 like Dredd, suggesting that Imd and Relish are direct
      substrates of Dredd. Among the seven Drosophila caspases, we find that Dredd
      uniquely promotes Imd and Relish processing, and purified recombinant Dredd
      cleaves Imd and Relish in vitro. In addition, interdomain cleavage of Dredd is
      not required for Imd or Relish processing and is not observed during immune
      stimulation. Baculovirus p35, a suicide substrate of executioner caspases, is not
      cleaved by purified Dredd in vitro. Consistent with this biochemistry but
      contrary to earlier reports, p35 does not interfere with Imd signaling in S2*
      cells or in vivo. 

PMID- 24891503
TI  - Roles for trafficking and O-linked glycosylation in the turnover of model cell
      surface proteins.
AB  - Proteins targeted to the plasma membrane (PM) of cells are degraded at different
      rates. Sorting motifs contained within the cytoplasmic domains of transmembrane
      proteins, post-translational modifications (e.g. ubiquitination), and assembly
      into multiprotein or protein-lipid complexes all may affect the efficiency of
      endocytosis and recycling and influence the delivery to degradative compartments.
      Using the SNAP-tag labeling system, we examined the turnover of a model PM
      protein, the alpha chain of the interleukin-2 receptor (Tac). The surface
      lifetimes of SNAP-Tac fusions were influenced by their mode of entry into cells
      (clathrin-dependent versus clathrin-independent), their orientation in the PM
      (transmembrane versus glycosylphosphatidylinositol-anchored), and ubiquitination
      in their cytosolic domains. In addition, shedding of SNAP-Tac into the medium was
      greatly influenced by its O-linked glycosylation status. For a number of PM
      proteins, delivery to lysosomes and ectodomain shedding represent distinct
      parallel mechanisms to determine protein half-life. 

PMID- 24891504
TI  - Involvement of microRNAs in the regulation of muscle wasting during catabolic
      conditions.
AB  - Loss of muscle proteins and the consequent weakness has important clinical
      consequences in diseases such as cancer, diabetes, chronic heart failure, and in
      aging. In fact, excessive proteolysis causes cachexia, accelerates disease
      progression, and worsens life expectancy. Muscle atrophy involves a common
      pattern of transcriptional changes in a small subset of genes named atrophy
      related genes or atrogenes. Whether microRNAs play a role in the atrophy program
      and muscle loss is debated. To understand the involvement of miRNAs in atrophy we
      performed miRNA expression profiling of mouse muscles under wasting conditions
      such as fasting, denervation, diabetes, and cancer cachexia. We found that the
      miRNA signature is peculiar of each catabolic condition. We then focused on
      denervation and we revealed that changes in transcripts and microRNAs expression
      did not occur simultaneously but were shifted. Indeed, whereas transcriptional
      control of the atrophy-related genes peaks at 3 days, changes of miRNA expression
      maximized at 7 days after denervation. Among the different miRNAs, microRNA-206
      and -21 were the most induced in denervated muscles. We characterized their
      pattern of expression and defined their role in muscle homeostasis. Indeed, in
      vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21
      were sufficient and required for atrophy program. In silico and in vivo
      approaches identified transcription factor YY1 and the translational initiator
      factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important
      for fine-tuning the atrophy program and their modulation can be a novel potential
      therapeutic approach to counteract muscle loss and weakness in catabolic
      conditions. 

PMID- 24891505
TI  - Two amino acid residues confer different binding affinities of Abelson family
      kinase SRC homology 2 domains for phosphorylated cortactin.
AB  - The closely related Abl family kinases, Arg and Abl, play important non-redundant
      roles in the regulation of cell morphogenesis and motility. Despite similar N
      terminal sequences, Arg and Abl interact with different substrates and binding
      partners with varying affinities. This selectivity may be due to slight
      differences in amino acid sequence leading to differential interactions with
      target proteins. We report that the Arg Src homology (SH) 2 domain binds two
      specific phosphotyrosines on cortactin, a known Abl/Arg substrate, with over 10
      fold higher affinity than the Abl SH2 domain. We show that this significant
      affinity difference is due to the substitution of arginine 161 and serine 187 in
      Abl to leucine 207 and threonine 233 in Arg, respectively. We constructed Abl SH2
      domains with R161L and S187T mutations alone and in combination and find that
      these substitutions are sufficient to convert the low affinity Abl SH2 domain to
      a higher affinity "Arg-like" SH2 domain in binding to a phospho-cortactin
      peptide. We crystallized the Arg SH2 domain for structural comparison to existing
      crystal structures of the Abl SH2 domain. We show that these two residues are
      important determinants of Arg and Abl SH2 domain binding specificity. Finally, we
      expressed Arg containing an "Abl-like" low affinity mutant Arg SH2 domain
      (L207R/T233S) and find that this mutant, although properly localized to the cell
      periphery, does not support wild type levels of cell edge protrusion. Together,
      these observations indicate that these two amino acid positions confer different
      binding affinities and cellular functions on the distinct Abl family kinases. 

PMID- 24891506
TI  - Nucleosomes suppress the formation of double-strand DNA breaks during attempted
      base excision repair of clustered oxidative damages.
AB  - Exposure to ionizing radiation can produce multiple, clustered oxidative lesions
      in DNA. The near simultaneous excision of nearby lesions in opposing DNA strands
      by the base excision repair (BER) enzymes can produce double-strand DNA breaks
      (DSBs). This attempted BER accounts for many of the potentially lethal or
      mutagenic DSBs that occur in vivo. To assess the impact of nucleosomes on the
      frequency and pattern of BER-dependent DSB formation, we incubated nucleosomes
      containing oxidative damages in opposing DNA strands with selected DNA
      glycosylases and human apurinic/apyrimidinic endonuclease 1. Overall, nucleosomes
      substantially suppressed DSB formation. However, the degree of suppression varied
      as a function of (i) the lesion type and DNA glycosylase tested, (ii) local
      sequence context and the stagger between opposing strand lesions, (iii) the
      helical orientation of oxidative lesions relative to the underlying histone
      octamer, and (iv) the distance between the lesion cluster and the nucleosome
      edge. In some instances the binding of a BER factor to one nucleosomal lesion
      appeared to facilitate binding to the opposing strand lesion. DSB formation did
      not invariably lead to nucleosome dissolution, and in some cases, free DNA ends
      resulting from DSB formation remained associated with the histone octamer. These
      observations explain how specific structural and dynamic properties of
      nucleosomes contribute to the suppression of BER-generated DSBs. These studies
      also suggest that most BER-generated DSBs will occur in linker DNA and in genomic
      regions associated with elevated rates of nucleosome turnover or remodeling. 

PMID- 24891507
TI  - Metabolite proofreading in carnosine and homocarnosine synthesis: molecular
      identification of PM20D2 as beta-alanyl-lysine dipeptidase.
AB  - Carnosine synthase is the ATP-dependent ligase responsible for carnosine (beta
      alanyl-histidine) and homocarnosine (gamma-aminobutyryl-histidine) synthesis in
      skeletal muscle and brain, respectively. This enzyme uses, also at substantial
      rates, lysine, ornithine, and arginine instead of histidine, yet the resulting
      dipeptides are virtually absent from muscle or brain, suggesting that they are
      removed by a "metabolite repair" enzyme. Using a radiolabeled substrate, we found
      that rat skeletal muscle, heart, and brain contained a cytosolic beta-alanyl
      lysine dipeptidase activity. This enzyme, which has the characteristics of a
      metalloenzyme, was purified ~ 200-fold from rat skeletal muscle. Mass
      spectrometry analysis of the fractions obtained at different purification stages
      indicated parallel enrichment of PM20D2, a peptidase of unknown function
      belonging to the metallopeptidase 20 family. Western blotting showed coelution of
      PM20D2 with beta-alanyl-lysine dipeptidase activity. Recombinant mouse PM20D2
      hydrolyzed beta-alanyl-lysine, beta-alanyl-ornithine, gamma-aminobutyryl-lysine,
      and gamma-aminobutyryl-ornithine as its best substrates. It also acted at lower
      rates on beta-alanyl-arginine and gamma-aminobutyryl-arginine but virtually not
      on carnosine or homocarnosine. Although acting preferentially on basic dipeptides
      derived from beta-alanine or gamma-aminobutyrate, PM20D2 also acted at lower
      rates on some "classic dipeptides" like alpha-alanyl-lysine and alpha-lysyl
      lysine. The same activity profile was observed with human PM20D2, yet this enzyme
      was ~ 100-200-fold less active on all substrates tested than the mouse enzyme.
      Cotransfection in HEK293T cells of mouse or human PM20D2 together with carnosine
      synthase prevented the accumulation of abnormal dipeptides (beta-alanyl-lysine,
      beta-alanyl-ornithine, gamma-aminobutyryl-lysine), thus favoring the synthesis of
      carnosine and homocarnosine and confirming the metabolite repair role of PM20D2.

PMID- 24891508
TI  - Genomic determinants of gene regulation by 1,25-dihydroxyvitamin D3 during
      osteoblast-lineage cell differentiation.
AB  - The biological effects of 1alpha,25-dihydroxyvitamin D3 (1,25 (OH)2D3) on
      osteoblast differentiation and function differ significantly depending upon the
      cellular state of maturation. To explore this phenomenon mechanistically, we
      examined the impact of 1,25(OH)2D3 on the transcriptomes of both pre-osteoblastic
      (POBs) and differentiated osteoblastic (OBs) MC3T3-E1 cells, and assessed
      localization of the vitamin D receptor (VDR) at sites of action on a genome-scale
      using ChIP sequence analysis. We observed that the 1,25(OH)2D3-induced
      transcriptomes of POBs and OBs were quantitatively and qualitatively different,
      supporting not only the altered biology observed but the potential for a change
      in VDR interaction at the genome as well. This idea was confirmed through
      discovery that VDR cistromes in POBs and OBs were also strikingly different.
      Depletion of VDR-binding sites in OBs, due in part to reduced VDR expression, was
      the likely cause of the loss of VDR-target gene interaction. Continued novel
      regulation by 1,25(OH)2D3, however, suggested that factors in addition to the VDR
      might also be involved. Accordingly, we show that transcriptomic modifications
      are also accompanied by changes in genome binding of the master osteoblast
      regulator RUNX2 and the chromatin remodeler CCAAT/enhancer-binding protein beta.
      Importantly, genome occupancy was also highlighted by the presence of epigenetic
      enhancer signatures that were selectively changed in response to both
      differentiation and 1,25(OH)2D3. The impact of VDR, RUNX2, and C/EBPbeta on
      osteoblast differentiation is exemplified by their actions at the Runx2 and Sp7
      gene loci. We conclude that each of these mechanisms may contribute to the
      diverse actions of 1,25(OH)2D3 on differentiating osteoblasts. 

PMID- 24891509
TI  - The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1)
      protein to the viral ribonucleoprotein to mediate nuclear export.
AB  - In influenza A virus-infected cells, replication and transcription of the viral
      genome occurs in the nucleus. To be packaged into viral particles at the plasma
      membrane, encapsidated viral genomes must be exported from the nucleus.
      Intriguingly, the nuclear export protein (NEP) is involved in both processes.
      Although NEP stimulates viral RNA synthesis by binding to the viral polymerase,
      its function during nuclear export implicates interaction with viral
      ribonucleoprotein (vRNP)-associated M1. The observation that both interactions
      are mediated by the C-terminal moiety of NEP raised the question whether these
      two features of NEP are linked functionally. Here we provide evidence that the
      interaction between M1 and the vRNP depends on the NEP C terminus and its
      polymerase activity-enhancing property for the nuclear export of vRNPs. This
      suggests that these features of NEP are linked functionally. Furthermore, our
      data suggest that the N-terminal domain of NEP interferes with the stability of
      the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible
      intramolecular interaction with the NEP C terminus. On the basis of our data, we
      propose a new model for the assembly of the nuclear export complex of Influenza A
      vRNPs. 

PMID- 24891511
TI  - Endoplasmic reticulum-associated degradation of Niemann-Pick C1: evidence for the
      role of heat shock proteins and identification of lysine residues that accept
      ubiquitin.
AB  - Most cases with Niemann-Pick disease type C carry mutations in NPC1. Some of the
      mutations, including the most frequent I1061T, give rise to unstable proteins
      selected for endoplasmic reticulum-associated degradation. The purpose of the
      current study was to shed mechanistic insights into the degradation process. A
      proteasome inhibitor MG132 prolonged the life span of the wild-type NPC1
      expressed in COS cells. The expressed protein associated with multiple chaperones
      including heat shock protein 90 (Hsp90), Hsp70, heat shock cognate protein 70
      (Hsc70), and calnexin. Accordingly, expression of an E3 ligase CHIP (carboxyl
      terminus of Hsp70-interacting protein) enhanced MG132-induced accumulation of
      ubiquitylated NPC1. Co-expression and RNAi knockdown experiments in HEK cells
      indicated that Hsp70/Hsp90 stabilized NPC1, whereas Hsc70 destabilized it. In
      human fibroblasts carrying the I1061T mutation, adenovirus-mediated expression of
      Hsp70 or treatment with an HSP-inducer geranylgeranylacetone (GGA) increased the
      level of the mutant protein. In GGA-treated cells, the rescued protein was
      localized in the late endosome and ameliorated cholesterol accumulation. MALDI
      TOF mass spectrometry revealed three lysine residues at amino acids 318, 792, and
      1180 as potential ubiquitin-conjugation sites. Substitutions of the three
      residues with alanine yielded a mutant protein with a steady-state level more
      than three times higher than that of the wild-type. Introduction of the same
      substitutions to the I1061T mutant resulted in an increase in its protein level
      and functional restoration. These findings indicated the role of HSPs in quality
      control of NPC1 and revealed the role of three lysine residues as ubiquitin
      conjugation sites. 

PMID- 24891510
TI  - Calpain-dependent cleavage of N-cadherin is involved in the progression of post
      myocardial infarction remodeling.
AB  - Enzymatic proteolysis by calpains, Ca(2+)-dependent intracellular cysteine
      proteases, has been implicated in pathological processes such as cellular
      degeneration or death. Here, we investigated the role of calpain activation in
      the hearts subjected to myocardial infarction. We produced myocardial infarction
      in Cast(-/-) mice deficient for calpastatin, the specific endogenous inhibitory
      protein for calpains, and Cast(+/+) mice. The activity of cardiac calpains in
      Cast(+/+) mice was not elevated within 1 day but showed a gradual elevation after
      7 days following myocardial infarction, which was further pronounced in Cast(-/-)
      mice. Although the prevalence of cardiomyocyte death was indistinguishable
      between Cast(-/-) and Cast(+/+) mice, Cast(-/-) mice exhibited profound
      contractile dysfunction and chamber dilatation and showed a significant reduction
      in survival rate after myocardial infarction as compared with Cast(+/+) mice.
      Notably, immunofluorescence revealed that at 28 days after myocardial infarction,
      calpains were activated in cardiomyocytes exclusively at the border zone and that
      Cast(-/-) mice showed higher intensity and a broader extent of calpain activation
      at the border zone than Cast(+/+) mice. In the border zone of Cast(-/-) mice,
      pronounced activation of calpains was associated with a decrease in N-cadherin
      expression and up-regulation of molecular markers for cardiac hypertrophy and
      fibrosis. In cultured rat neonatal cardiomyocytes, calpain activation by
      treatment with ionomycin induced cleavage of N-cadherin and decreased expression
      levels of beta-catenin and connexin 43, which was attenuated by calpain
      inhibitor. These results thus demonstrate that activation of calpains
      disassembles cell-cell adhesion at intercalated discs by degrading N-cadherin and
      thereby promotes left ventricular remodeling after myocardial infarction. 

PMID- 24891514
TI  - Comment on "Results of Proximal Medial Gastrocnemius Release for Achilles
      Tendinopathy".

PMID- 24891515
TI  - Author Response.

PMID- 24891512
TI  - Nitrosothiol formation and protection against Fenton chemistry by nitric oxide
      induced dinitrosyliron complex formation from anoxia-initiated cellular
      chelatable iron increase.
AB  - Dinitrosyliron complexes (DNIC) have been found in a variety of pathological
      settings associated with (*)NO. However, the iron source of cellular DNIC is
      unknown. Previous studies on this question using prolonged (*)NO exposure could
      be misleading due to the movement of intracellular iron among different sources.
      We here report that brief (*)NO exposure results in only barely detectable DNIC,
      but levels increase dramatically after 1-2 h of anoxia. This increase is similar
      quantitatively and temporally with increases in the chelatable iron, and brief
      (*)NO treatment prevents detection of this anoxia-induced increased chelatable
      iron by deferoxamine. DNIC formation is so rapid that it is limited by the
      availability of (*)NO and chelatable iron. We utilize this ability to selectively
      manipulate cellular chelatable iron levels and provide evidence for two cellular
      functions of endogenous DNIC formation, protection against anoxia-induced
      reactive oxygen chemistry from the Fenton reaction and formation by
      transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these
      high chelatable iron levels are comparable with DNIC levels and suggest that
      under these conditions, both DNIC and RSNO are the most abundant cellular adducts
      of (*)NO. 

PMID- 24891513
TI  - Wnt5a promotes inflammatory responses via nuclear factor kappaB (NF-kappaB) and
      mitogen-activated protein kinase (MAPK) pathways in human dental pulp cells.
AB  - Wnt5a has been found recently to be involved in inflammation regulation through a
      mechanism that remains unclear. Immunohistochemical staining of infected human
      dental pulp and tissue from experimental dental pulpitis in rats showed that
      Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental
      pulp cells (HDPCs) after TNF-alpha stimulation compared with control cells. We
      then investigated the role of Wnt5a in HDPCs. In the presence of TNF-alpha, Wnt5a
      further increased the production of cytokines/chemokines, whereas Wnt5a knockdown
      markedly reduced cytokine/ chemokine production induced by TNF-alpha. In
      addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and,
      in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed
      by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially
      with those induced by TNF-alpha. However, no TNF-alpha and IL-1beta was detected
      after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of
      Wnt5a-treated HDPCs significantly increased macrophage migration, which supports
      a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in
      human dental pulp inflammation. Finally, Wnt5a participates in dental pulp
      inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-kappaB
      dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that
      drives the integration of cytokines and chemokines, acts downstream of TNF-alpha.

PMID- 24891518
TI  - Genome-wide DNA methylation profiling identifies a folate-sensitive region of
      differential methylation upstream of ZFP57-imprinting regulator in humans.
AB  - Folate intake during pregnancy may affect the regulation of DNA methylation
      during fetal development. The genomic regions in the offspring that may be
      sensitive to folate exposure during in utero development have not been
      characterized. Using genome-scale profiling, we investigated DNA methylation in 2
      immune cell types (CD4(+) and antigen-presenting cells) isolated from neonatal
      cord blood, selected on the basis of in utero folate exposure. High-folate (HF;
      n=11) and low-folate (LF; n=12) groups were selected from opposite extremes of
      maternal serum folate levels measured in the last trimester of pregnancy. A
      comparison of these groups revealed differential methylation at 7 regions across
      the genome. By far, the biggest effect observed was hypomethylation of a 923 bp
      region 3 kb upstream of the ZFP57 transcript, a regulator of DNA methylation
      during development, observed in both cell types. Levels of H3/H4 acetylation at
      ZFP57 promoter and ZFP57 mRNA expression were higher in CD4(+) cells in the HF
      group relative to the LF group. Hypomethylation at this region was replicated in
      an independent sample set. These data suggest that exposure to folate has effects
      on the regulation of DNA methylation during fetal development, and this may be
      important for health and disease.

PMID- 24891520
TI  - Phosphorylation of tropomodulin1 contributes to the regulation of actin filament
      architecture in cardiac muscle.
AB  - Tropomodulin1 (Tmod1) is an actin-capping protein that plays an important role in
      actin filament pointed-end dynamics and length in striated muscle. No mechanisms
      have been identified to explain how Tmod1's functional properties are regulated.
      The purpose of this investigation was to explore the functional significance of
      the phosphorylation of Tmod1 at previously identified Thr54. Rat cardiomyocytes
      were assessed for phosphorylation of Tmod1 using Pro-Q Diamond staining and (32)P
      labeling. Green fluorescent protein-tagged phosphorylation-mimic (T54E) and
      phosphorylation-deficient (T54A) versions of Tmod1 were expressed in cultured
      cardiomyocytes, and the ability of these mutants to assemble and restrict actin
      lengths was observed. We report for the first time that Tmod1 is phosphorylated
      endogenously in cardiomyocytes, and phosphorylation at Thr54 causes a significant
      reduction in the ability of Tmod1 to assemble to the pointed end compared with
      that of the wild type (WT; 48 vs. 78%, respectively). In addition, overexpression
      of Tmod1-T54E restricts actin filament lengths by only ~3%, whereas Tmod1-WT
      restricts the lengths significantly by ~8%. Finally, Tmod1-T54E altered the actin
      filament-capping activity in polymerization assays. Taken together, our data
      suggest that pointed-end assembly and Tmod1's thin filament length regulatory
      function are regulated by its phosphorylation state.

PMID- 24891519
TI  - Kv1.3 channel-blocking immunomodulatory peptides from parasitic worms:
      implications for autoimmune diseases.
AB  - The voltage-gated potassium (Kv) 1.3 channel is widely regarded as a therapeutic
      target for immunomodulation in autoimmune diseases. ShK-186, a selective
      inhibitor of Kv1.3 channels, ameliorates autoimmune diseases in rodent models,
      and human phase 1 trials of this agent in healthy volunteers have been completed.
      In this study, we identified and characterized a large family of Stichodactyla
      helianthus toxin (ShK)-related peptides in parasitic worms. Based on phylogenetic
      analysis, 2 worm peptides were selected for study: AcK1, a 51-residue peptide
      expressed in the anterior secretory glands of the dog-infecting hookworm
      Ancylostoma caninum and the human-infecting hookworm Ancylostoma ceylanicum, and
      BmK1, the C-terminal domain of a metalloprotease from the filarial worm Brugia
      malayi. These peptides in solution adopt helical structures closely resembling
      that of ShK. At doses in the nanomolar-micromolar range, they block native Kv1.3
      in human T cells and cloned Kv1.3 stably expressed in L929 mouse fibroblasts.
      They preferentially suppress the proliferation of rat CCR7(-) effector memory T
      cells without affecting naive and central memory subsets and inhibit the delayed
      type hypersensitivity (DTH) response caused by skin-homing effector memory T
      cells in rats. Further, they suppress IFNgamma production by human T lymphocytes.
      ShK-related peptides in parasitic worms may contribute to the potential
      beneficial effects of probiotic parasitic worm therapy in human autoimmune
      diseases.

PMID- 24891521
TI  - Altered hepatic sulfur metabolism in cystathionine beta-synthase-deficient
      homocystinuria: regulatory role of taurine on competing cysteine oxidation
      pathways.
AB  - Cystathionine beta-synthase-deficient homocystinuria (HCU) is a serious life
      threatening inborn error of sulfur metabolism with poorly understood pathogenic
      mechanisms. We investigated the effect of HCU on hepatic cysteine oxidation in a
      transgenic mouse model of the disease. Cysteine dioxygenase (CDO) protein levels
      were 90% repressed without any change in mRNA levels. Cysteinesulfinic acid
      decarboxylase (CSAD) was induced at both the mRNA (8-fold) and protein (15-fold)
      levels. Cysteine supplementation normalized CDO protein levels without reversing
      the induction of CSAD. Regulatory changes in CDO and CSAD expression were
      proportional to homocysteine elevation, indicating a possible threshold effect.
      Hepatic and blood taurine levels in HCU animals were decreased by 21 and 35%,
      respectively, and normalized by cysteine supplementation. Expression of the
      cytoplasmic (GOT1) and mitochondrial (GOT2) isoforms of glutamic-oxaloacetic
      transaminase were repressed in HCU animals by 86 and 30%, respectively. HCU
      induced regulatory changes in CSAD, CDO, and GOT1 expression were normalized by
      taurine supplementation, indicating that cysteine is not the only sulfur compound
      that regulates hepatic cysteine oxidation. Collectively, our results indicate
      that HCU induces significant alterations of sulfur metabolism with the potential
      to contribute to pathogenesis and that cysteine and taurine have the potential to
      serve as adjunctive treatments in this disease.

PMID- 24891522
TI  - Eosinophils control the resolution of inflammation and draining lymph node
      hypertrophy through the proresolving mediators and CXCL13 pathway in mice.
AB  - Resolution of inflammation is critical to restoration of tissue function after an
      inflammatory response. We previously demonstrated that 12/15-lipoxygenase (12/15
      LOX)-expressing eosinophils contribute to this process in murine zymosan-induced
      peritonitis. In this study, eosinophils promoted resolution by regulating
      expression of macrophage CXCL13. Microarray analysis revealed that eosinophils
      significantly increased (~3-fold) the expression of macrophage CXCL13 by a 12/15
      LOX-dependent mechanism. CXCL13 depletion caused a resolution defect, with the
      reduced appearance of phagocytes carrying engulfed zymosan in the draining lymph
      nodes. Inflamed lymph node hypertrophy, a critical feature of the resolution
      process, was reduced by ~60% in eosinophil-deficient mice, and adoptive transfer
      of eosinophils or administration of CXCL13 corrected this defect. Administration
      of the 12/15-LOX-derived mediator lipoxin A4 (LXA4) increased the expression of
      CXCL13 and restored the defect of lymph node hypertrophy in eosinophil-deficient
      mice. These results demonstrate that eosinophils control the resolution of
      inflammation and draining lymph node hypertrophy through proresolving lipid
      mediators and the CXCL13 pathway in mice.

PMID- 24891523
TI  - A camelid antibody candidate for development of a therapeutic agent against
      Hemiscorpius lepturus envenomation.
AB  - Hemiscorpius lepturus scorpionism poses one of the most dangerous health problems
      in many parts of the world. The common therapy consists of using antivenom
      antibody fragments derived from a polyclonal immune response raised in horses.
      However, this immunotherapy creates serious side effects, including anaphylactic
      shock sometimes even leading to death. Thus, many efforts have been made to
      introduce new replacement therapeutics that cause less adverse reactions. One of
      the most attractive approaches to replacing the available therapy is offered by
      single-domain antibody fragments, or nanobodies (Nbs). We immunized dromedaries
      with H. lepturus toxin and identified a functional recombinant Nb (referred to as
      F7Nb) against heminecrolysin (HNc), the major known hemolytic and dermonecrotic
      fraction of H. lepturus venom. This Nb was retrieved from the immune library by
      phage display selection. The in vitro neutralization tests indicated that 17.5
      nmol of the F7Nb can inhibit 45% of the hemolytic activity of 1 EC100 (7.5
      MUg/ml) of HNc. The in vivo neutralization tests demonstrated that F7Nb had good
      antihemolytic and antidermonecrotic effects against HNc in all tested mice.
      Surprisingly, F7Nb (8.75 nmol) neutralized 1 LD100 of HNc (10 MUg) via an
      intracerebroventricular route or 1 LD100 (80 MUg) via a subcutaneous route. All
      of the control mice died. Hence, this Nb is a potential leading novel candidate
      for treating H. lepturus scorpionism in the near future.

PMID- 24891525
TI  - Peer training of community health workers to improve heart health among African
      American women.
AB  - INTRODUCTION: Training community health workers (CHWs) builds a workforce that is
      essential to addressing the chronic disease crisis. This article describes a
      highly replicable CHW training program that targets heart disease risk among
      African American women. BACKGROUND: African American women suffer
      disproportionately from heart disease mortality and morbidity. Well-trained CHWs
      are uniquely positioned to close this disparity gap. Method. We used a Learning
      Circle approach to train CHWs in heart health education. The curriculum blended
      web-based, self-directed learning and in-person peer coaching. CHWs learned
      through (a) peer-to-peer sharing, (b) problem solving and brainstorming, and (c)
      leadership and experiential activities. Training evaluation measures were CHWs'
      (a) self-confidence, (b) heart health knowledge, (c) satisfaction with training,
      (d) training retention, and (e) replication of training within 90 days after
      training. RESULTS: This training resulted in appreciable effects on four of five
      outcome measures. Heart health knowledge increased significantly among
      experienced CHWs (p = .011). CHWs were satisfied with training and retention was
      100%. CHWs initiated and subsequently delivered 122 person hours of community
      heart health education and CHW training in their communities.
      DISCUSSION/CONCLUSION: CHW heart health training using Learning Circles is a
      practical and replicable method of training CHWs and holds significant potential
      for building capacity in resource-poor community organizations.

PMID- 24891524
TI  - Visualization of the pH-dependent dynamic distribution of G2A in living cells.
AB  - G2A (from G2 accumulation) receptor is a member of the proton-sensing G-protein
      coupled receptor (GPCR) family and induces signal transduction events that
      regulate the cell cycle, proliferation, oncogenesis, and immunity. The mechanism
      by which G2A-mediated signal transduction is regulated by the extracellular pH
      remains unresolved. Here, we first visualize the pH-dependent G2A distribution
      change in living cells by a sortase A-mediated pulse labeling technology: the
      short-peptide tag-fused human G2A on human embryo kidney HEK293T cell surfaces
      was labeled with a small fluorescent dye in the presence of
      lysophosphatidylcholine, and the labeled G2A was chased at acidic and neutral pHs
      in real time by microscope time course observations. G2A internalization from
      cell surfaces into intracellular compartments was observed to be inhibited under
      acidic pH conditions, and this inhibition was relieved at neutral pH.
      Additionally, the internalized G2A was redistributed onto cell surfaces by
      jumping from a neutral to an acidic pH. From quantitative image analysis data, we
      conclude the amount of G2A on the cell surface was controlled by suppressing the
      G2A internalization rate by one-tenth in response to the extracellular acidic pH,
      and this acidic pH-induced G2A accumulation on cell surfaces may be explained by
      proton-induced dissociation of G2A from endocytic machinery.

PMID- 24891527
TI  - Weapon Possession Among College Students: A Study From a Midwestern University.
AB  - Weapon possession on college campuses causes great concern, but there remains a
      lack of research examining the determinants of this phenomenon. Previous studies
      addressing weapon possession have primarily focused on either K-12 or the general
      adult population. Unlike previous studies, this study examined the weapon
      possession among college students using data collected from a mid-sized
      university in Missouri, and 451 students participated. Weapon possession and
      other theoretical factors were measured through the self-administered survey.
      Logistical regression analysis revealed that weapon socialization was the most
      significant factor in predicting student weapon carrying. Also, gender and age
      were significant factors in explaining campus-based weapon possession. This
      research has a limitation with generalizability because the data were collected
      from only a single university with convenient sampling. Future studies need to
      cover a wider range of college students from a variety of different universities
      with random sampling. 

PMID- 24891526
TI  - Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal
      motility and reduces abdominal pain in mouse models mimicking irritable bowel
      syndrome.
AB  - The opioid and cannabinoid systems play a crucial role in multiple physiological
      processes in the central nervous system and in the periphery. Selective opioid as
      well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on
      gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and
      in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin
      A, can interact with both systems and demonstrate therapeutic effects. We used
      mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the
      influence of PR-38 on the central nervous system by measurement of motoric
      parameters and exploratory behaviors in mice. Subsequently, we investigated the
      pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral
      administration. PR-38 significantly inhibited mouse colonic motility in vitro and
      in vivo. Administration of PR-38 significantly prolonged the whole GI transit
      time, and this effect was mediated by u- and kappa-opioid receptors and the CB1
      receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking
      functional GI disorders. These data expand our understanding of the interactions
      between opioid and cannabinoid systems and their functions in the GI tract. We
      also provide a novel framework for the development of future potential treatments
      of functional GI disorders. 

PMID- 24891528
TI  - COPD: More options mean potentially better control.

PMID- 24891529
TI  - Insulin before surgery (November 2013).

PMID- 24891530
TI  - In reply.

PMID- 24891531
TI  - A comment on a CME test question (December 2013).

PMID- 24891532
TI  - Stress ulcer prophylaxis (January 2014).

PMID- 24891533
TI  - In reply.

PMID- 24891534
TI  - Albuminuria (January 2014).

PMID- 24891535
TI  - Q: Do patients who received only two doses of hepatitis B vaccine need a booster?

PMID- 24891536
TI  - Encephalopathy despite thiamine repletion during alcohol withdrawal.

PMID- 24891537
TI  - Role of imaging in endometriosis.
AB  - Endometriosis--the presence of endometrial tissue outside the uterine cavity--is
      first suspected on the basis of its signs and symptoms. The diagnosis is
      confirmed by imaging and surgery. Imaging, particularly transvaginal
      ultrasonography and magnetic resonance imaging, is essential to confirm the
      diagnosis and guide surgical treatment.

PMID- 24891538
TI  - Prescribing for the pregnant patient.
AB  - Prescribing in pregnancy can be challenging for providers facing insufficient
      information about drug safety, overestimation of the risk of medications by both
      the patient and the care provider, and increasing litigation costs. This article
      provides key concepts to consider when prescribing for a pregnant patient and
      offers practical advice for choosing the safest possible drug treatments. 

PMID- 24891539
TI  - Chronic obstructive pulmonary disease: an update for the primary physician.
AB  - Our understanding of how to manage chronic obstructive pulmonary disease (COPD)
      has advanced significantly over the past decade. Physicians should instill
      optimism for improved symptoms and quality of life in their patients with COPD, a
      previously stigmatized condition. 

PMID- 24891540
TI  - The mentally ill offender: failed reintegration and recidivism.

PMID- 24891541
TI  - The quest to prevent stroke in atrial fibrillation: fighting the fluttering heart
      in Singapore.

PMID- 24891542
TI  - FLAIR vascular hyperintensity resolution in a TIA patient: clinical-radiologic
      correlation.

PMID- 24891543
TI  - Practice variability in brain death determination: a call to action.

PMID- 24891544
TI  - Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis:
      case report.

PMID- 24891545
TI  - Clinical reasoning: a 24-year-old woman with progressive headache and somnolence.

PMID- 24891546
TI  - Clinical reasoning: a 72-year-old man with rapid cognitive decline and unilateral
      muscle jerks.

PMID- 24891547
TI  - Teaching neuroimages: posttraumatic neuroma-in-continuity of the right tibial
      nerve.

PMID- 24891548
TI  - Time to screening in the systems of support to increase colorectal cancer
      screening trial.
AB  - Understanding how interventions affect time to completion of colorectal cancer
      screening might assist in planning and delivering population-based screening
      interventions. The Systems of Support to Increase Colorectal Cancer Screening
      (SOS) study was conducted between 2008 and 2011 at 21 primary care medical
      centers in Western Washington. Participants in the study, ages 50 to 73 years,
      were eligible if they were enrolled in Group Health (Seattle, WA) and were due
      for colorectal cancer screening. Of note, 4,675 recruited participants were
      randomized to usual care or one of three interventions with incremental levels of
      systems of support for completion of colorectal cancer screening. We conducted
      time to screening analyses of the SOS data in years 1 and 2. We investigated
      whether these effects were time-varying. For year 1, the intervention effects on
      the time to completion of colorectal cancer screening were the strongest during
      the first two post-randomization months and then decreased, with no significant
      effect after the fifth month. For year 2, the intervention effects on the time to
      colorectal cancer screening increased from the first to the third month and then
      decreased, with no significant effect after the fifth month. Hence, each of the
      interventions to increase colorectal cancer screening had its greatest effect
      within the first 3 months after being offered to participants. Future studies
      should test whether booster interventions offered later could increase screening
      rate among those who remain unscreened. Additional research is needed to develop
      intervention strategies for colorectal cancer screening that focus on sustained
      behavior over time.

PMID- 24891549
TI  - Recent BRCAPRO upgrades significantly improve calibration.
AB  - The recent release of version 2.0-8 of the BayesMendel package contains an
      updated BRCAPRO risk prediction model, which includes revised modeling of
      contralateral breast cancer (CBC) penetrance, provisions for pedigrees of mixed
      ethnicity and an adjustment for mastectomies among family members. We estimated
      penetrance functions for CBC by a combination of parametric survival modeling of
      literature data and deconvolution of SEER9 data. We then validated the resulting
      updated model of CBC in BRCAPRO by comparing it with the previous release
      (BayesMendel 2.0-7), using pedigrees from the Cancer Genetics Network (CGN) Model
      Validation Study. Version 2.0-8 of BRCAPRO discriminates BRCA1/BRCA2 carriers
      from noncarriers with similar accuracy compared with the previous version
      (increase in AUC, 0.0043), is slightly more precise in terms of the root-mean
      square error (decrease in RMSE, 0.0108), and it significantly improves
      calibration (ratio of observed to expected events of 0.9765 in version 2.0-8,
      compared with 0.8910 in version 2.0-7). We recommend that the new version be used
      in clinical counseling, particularly in settings where families with CBC are
      common.

PMID- 24891550
TI  - Family history of colorectal cancer is not associated with colorectal cancer
      survival regardless of microsatellite instability status.
AB  - BACKGROUND: Individuals with a family history of colorectal cancer in first
      degree relatives have an elevated risk of developing colorectal cancer
      themselves, particularly colorectal cancer exhibiting high microsatellite
      instability (MSI-high). Given that MSI-high colorectal cancer is associated with
      a favorable prognosis, it is plausible that having a family history of colorectal
      cancer could, in turn, be favorably associated with colorectal cancer survival.
      METHODS: This study comprised N = 4,284 incident colorectal cancer cases enrolled
      in the Colon Cancer Family Registry via population-based cancer registries. Using
      Cox proportional hazards regression, we evaluated the association between family
      history and both overall and disease-specific survival, accounting for MSI status
      and tumor site via stratified analyses and statistical adjustment. RESULTS: There
      was no evidence of association between family history and overall [hazard ratio
      (HR), 0.92; 95% confidence interval (CI), 0.79-1.08] or disease-specific survival
      (HR, 1.03; 95% CI, 0.85-1.24) for all cases combined, after adjustment for MSI
      status or tumor site. Only for rectal cancer cases was colorectal cancer family
      history modestly associated with more favorable overall survival (HR, 0.75; 95%
      CI, 0.56-0.99). CONCLUSIONS: Although individuals with a family history of
      colorectal cancer were more likely to have MSI-high tumors than those with
      nonfamilial disease, this did not translate to a survival benefit. IMPACT:
      Overall, there is no evidence that family history of colorectal cancer is
      associated with colorectal cancer survival; however, specific mechanisms
      underlying family history may have prognostic impact and merit further study.

PMID- 24891551
TI  - Performance of the Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP)
      tumor biomarker for identifying recurrent disease in African American patients.
AB  - Evaluation of prostate cancer prognosis after surgery is increasingly relying
      upon genomic analyses of tumor DNA. We assessed the ability of the biomarker
      panel Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) to predict
      biochemical recurrence in 33 European American and 28 African American prostate
      cancer cases using genome-wide copy number data from a previous study. "Biomarker
      positive" was defined as >=20% of the 38 constituent copy number gain/loss GEMCaP
      loci affected in a given tumor; based on this threshold, the frequency of a
      positive biomarker was significantly lower in African Americans (n = 2; 7%) than
      European Americans (n = 11; 33%; P = 0.013). GEMCaP positivity was associated
      with risk of recurrence [hazard ratio (HR), 5.92; 95% confidence interval (CI),
      2.32-15.11; P = 3 * 10(-4)] in the full sample and among European Americans (HR,
      3.45; 95% CI, 1.13-10.51; P = 0.032) but was not estimable in African Americans
      due to the low rate of GEMCaP positivity. Overall, the GEMCaP recurrence positive
      predictive value (PPV) was 85%; in African Americans, PPV was 100%. When we
      expanded the definition of loss to include copy-neutral loss of heterozygosity
      (i.e., loss of one allele with concomitant duplication of the other), recurrence
      PPV was 83% for European American subjects. Under this definition, 5 African
      American subjects had a positive GEMCaP test value; 4 went on to develop
      biochemical recurrence (PPV = 80%). Our results suggest that the GEMCaP biomarker
      set could be an effective predictor for both European American and African
      American men diagnosed with localized prostate cancer who may benefit from
      immediate aggressive therapy after radical prostatectomy.

PMID- 24891552
TI  - How low should you go? Determining the optimal cutoff for exhaled carbon monoxide
      to confirm smoking abstinence when using cotinine as reference.
AB  - INTRODUCTION: Confirming abstinence during smoking cessation clinical trials is
      critical for determining treatment effectiveness. Several biological methods
      exist for verifying abstinence (e.g., exhaled carbon monoxide [CO], cotinine),
      and while cotinine provides a longer window of detection, it is not easily used
      in trials involving nicotine replacement therapy. The Society for Research on
      Nicotine and Tobacco's Subcommittee on Biochemical Verification cite 8-10 parts
      per million (ppm) for CO as a viable cutoff to determine abstinence; however,
      recent literature suggests this cutoff is likely too high and may overestimate
      the efficacy of treatment. METHODS: This study examined the relationship between
      CO and cotinine in a sample of 662 individuals participating in a smoking
      cessation clinical trial. A receiver operating characteristics curve was
      calculated to determine the percentage of false positives and false negatives at
      given CO levels when using cotinine as confirmation of abstinence. Differences
      were also examined across race and gender. RESULTS: A CO cutoff of 3 ppm (97.1%
      correct classification) most accurately distinguished smokers from nonsmokers.
      This same cutoff was accurate for both racial and gender groups. The standard
      cutoffs of 8 ppm (14.0% misclassification of smokers as abstainers) and 10 ppm
      (20.6% misclassification of smokers as abstainers) produced very high false
      negative rates and inaccurately identified a large part of the sample as being
      abstinent when their cotinine test identified them as still smoking. CONCLUSIONS:
      It is recommended that researchers and clinicians adopt a more stringent CO
      cutoff in the range of 3-4 ppm when complete abstinence from smoking is the goal.

PMID- 24891553
TI  - Clinical significance of isolated cytomegalovirus-infected gastrointestinal
      cells.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract is
      associated with high mortality in immunosuppressed patients. However, few studies
      have correlated blood CMV load with GI histopathological findings. Furthermore,
      there have been few studies determining the clinical significance of isolated CMV
      infection. DESIGN: Cases were selected for the diagnosis of GI CMV infection by
      searching the information system of a tertiary hospital. The electronic medical
      record was reviewed for each case to determine blood viral load,
      clinicopathological features at the time of diagnosis and clinical outcomes after
      discharge. RESULTS: In all, 30 patients with CMV-positive intestinal biopsies
      confirmed by immunohistochemistry (IHC) were identified. All were
      immunosuppressed. CMV inclusions were also recognized by hematoxylin and eosin
      stain in 27% of the cases, and the remaining cases were identified by IHC alone.
      CMV blood load was only positive in 17% of the cases; 8 cases had only isolated
      CMV-infected cells (0.1-0.5 IHC count/high-power field), with the following
      outcomes: worsening symptoms that responded to antiviral therapy (n = 5);
      clinical improvement without treatment (n = 1); death without treatment (n = 2).
      CONCLUSIONS: CMV infection of the intestines is clinically significant but will
      not always present with classic viral cytopathic changes. IHC should be
      considered in any case where there is a clinical suspicion for CMV infection.
      Identification of isolated CMV infection by IHC should be considered clinically
      significant. Current blood viral load tests have poor sensitivity in detecting
      CMV intestinal infection. Future studies will investigate the predictive value of
      positive peripheral blood viral load in patients with intestinal symptoms.

PMID- 24891554
TI  - Metachronous myxofibrosarcoma and osteosarcoma: case report and review of the
      literature.
AB  - The occurrence of multiple primary sarcomas in one individual is very uncommon
      and the development of osteosarcoma as a second tumor following a soft tissue
      sarcoma is extremely rare. We report a case of a 62-year-old man who developed 2
      histologically distinct sarcomas: a soft tissue myxofibrosarcoma and vertebral
      osteosarcoma. This unusual case highlights the critical role of careful
      histopathological evaluation in distinguishing synchronous or metachronous
      neoplasia from metastatic tumor. To the best of the authors' knowledge, this is
      the first reported case of metachronous soft tissue myxofibrosarcoma and
      osteosarcoma. 

PMID- 24891555
TI  - Adenomatoid tumor of the small intestine: the first case report and review of the
      literature.
AB  - The case represents the first literature report of an adenomatoid tumor that
      arises primarily in the small intestine of a 44-year-old woman, who presented
      with intermittent upper abdominal pain accompanied by nausea and vomiting. The
      resected tumor was grossly unencapsulated and had a gray-tan color on its cut
      surface. Microscopically, it consisted of variably sized tubules and glandular
      spaces which involved the whole layers of the intestine. The mesothelial nature
      of the lesion was subsequently verified by the immunopositivity for
      pancytokeratin (AE1/AE3), HBME-1, calretinin, D2-40, and WT1 with cells lining
      the tubules and glandular spaces. Albeit very rare, adenomatoid tumor should be
      included in the differential diagnosis of tubular or glandular tumors occurring
      in the small intestine. 

PMID- 24891556
TI  - An epidemiological study to assess the prevalence of diabetic peripheral
      neuropathic pain among adults with diabetes attending private and institutional
      outpatient clinics in South Africa.
AB  - OBJECTIVE: To determine the prevalence of diabetic peripheral neuropathic pain
      (DPNP) among South African adults with type 1 or type 2 diabetes. METHODS: This
      cross-sectional study recruited patients with diabetes from 50
      institutional/private clinics. DPNP was diagnosed using Douleur Neuropathique 4
      (DN4) questionnaire (score >=4). Health-related quality-of-life (HRQoL) and sleep
      were assessed with EQ-5D and Daily Sleep Interference Scale (DSIS), respectively.
      RESULTS: Prevalence of DPNP was 30.3% (n = 1046). Risk of DPNP was significantly
      increased in people aged 50-64 years (odds ratio [OR] 1.71, 95% confidence
      intervals [CI] 1.21, 2.41), with diabetes for >=10 years (OR 1.55, 95% CI 1.15,
      2.08), female patients (OR 1.58, 95% CI 1.18, 2.12), and black patients (OR 1.71,
      95% CI 1.19, 2.46). Mean +/- SD EQ-5D and DSIS scores were 0.84 +/- 0.16 and 0.83
      +/- 1.90, respectively, in participants without DPNP versus 0.64 +/- 0.25 and
      3.62 +/- 2.96, respectively, in those with DPNP. CONCLUSIONS: DPNP is widely
      prevalent in South Africa. Despite its negative impact on HRQoL and sleep, DPNP
      is inadequately treated. DN4 is an easy-to-use, validated questionnaire that can
      be used widely as a DPNP screening tool in clinical practice.

PMID- 24891558
TI  - Components of job control and mortality: the Finnish Public Sector Study.
AB  - OBJECTIVES: Recent research from industrial employees suggests the components of
      job control might be differently associated with mortality; high skill discretion
      with lower but high decision authority with higher mortality. This observation
      has not been confirmed in other cohorts. METHODS: The purpose of this study is to
      further examine the association of skill discretion and decision authority with
      all-cause and cause-specific mortality in an independent cohort of 60,202 public
      sector employees from the Finnish Public Sector study by stratifying analyses by
      sex and socioeconomic status. RESULTS: High skill discretion and high decision
      authority were associated with lower all-cause mortality rates in white-collar
      women. By contrast, high decision authority was associated with higher all-cause
      mortality rates in blue-collar women. No robust association between skill
      discretion, decision authority and mortality was observed among men. There were
      no robust associations with cause-specific mortality rates. CONCLUSIONS: These
      results suggest that the associations between components of job control and
      mortality are mixed and may vary depending on sex and socioeconomic status.

PMID- 24891557
TI  - Respiratory symptoms and lung function abnormalities related to work at a
      flavouring manufacturing facility.
AB  - OBJECTIVES: To better understand respiratory symptoms and lung function in
      flavouring manufacturing workers. METHODS: We offered a questionnaire and lung
      function testing to the current workforce of a flavouring manufacturing facility
      that had transitioned away from diacetyl and towards substitutes in recent years.
      We examined symptoms, spirometric parameters and diffusing capacity measurements
      by exposure variables, including facility tenure and time spent daily in
      production areas. We used linear and logistic regression to develop final models
      adjusted for age and smoking status. RESULTS: A total of 367 (93%) current
      workers participated. Shortness of breath was twice as common in those with
      tenure >= 7 years (OR 2.0, 95% CI 1.1 to 3.6). Other chest symptoms were
      associated with time spent daily in production. Participants who spent >= 1 h
      daily in production areas had twice the odds of any spirometric abnormality (OR
      2.3; 95% CI 1.1 to 5.3) and three times the odds of low diffusing capacity (OR
      2.8; 95% CI 0.9 to 9.4) than other participants. Mean spirometric parameters were
      significantly lower in those with tenure >= 7 years and those who spent >= 1 h
      daily in production. Mean diffusing capacity parameters were significantly lower
      in those with tenure >= 7 years. Differences in symptoms and lung function could
      not be explained by age, smoking status or employment at another flavouring
      plant. CONCLUSIONS: Symptoms and lung function findings were consistent with
      undiagnosed or subclinical obliterative bronchiolitis and associated with
      workplace exposures. Further efforts to lower exposures to flavouring chemicals,
      including diacetyl substitutes, are warranted.

PMID- 24891559
TI  - Screening for ADHD in a Sample of Egyptian Adolescent School Students.
AB  - OBJECTIVE: To screen for ADHD in a sample of Egyptian adolescent students, and
      study the distribution of different subtypes of ADHD, associated comorbidities,
      and sociodemographic correlates. METHOD: A total of 925 adolescents were randomly
      selected and screened by the Conners-Wells' Adolescent Self-Report Scale-Short
      form (CASS:S), and potential cases were further assessed by the Kiddie Schedule
      for Affective Disorders and Schizophrenia-Present and Lifetime versions (K-SADS
      PL). RESULTS: A total of 87 students (9.4%) had potential ADHD diagnosis with
      evident preponderance in boys (13.8%, n = 58) than in girls (5.8%, n = 29) with a
      ratio of 2:1 ( p = .000, chi2 = 17.328). The hyperactive-impulsive subtype
      comprised the majority of cases (54.7%, n = 41). Psychiatric comorbidity was
      invariably present (85.1%, n = 74). Nearly half the cases had poor academic
      achievement (43.7%, n = 34). Positive correlates included family history of
      psychiatric disorders, the order of birth, and parental disharmony. CONCLUSION:
      ADHD is prevalent in Egyptian adolescents and is associated with high psychiatric
      comorbidity and a pronounced effect on academic performance.

PMID- 24891560
TI  - Quality control of photosystem II: direct imaging of the changes in the thylakoid
      structure and distribution of FtsH proteases in spinach chloroplasts under light
      stress.
AB  - Under light stress, the reaction center-binding protein D1 of PSII is photo
      oxidatively damaged and removed from PSII complexes by proteases located in the
      chloroplast. A protease considered to be responsible for degradation of the
      damaged D1 protein is the metalloprotease FtsH. We showed previously that the
      active hexameric FtsH protease is abundant at the grana margin and the grana end
      membranes, and this homo-complex removes the photodamaged D1 protein in the
      grana. Here, we showed a change in the distribution of FtsH in spinach thylakoids
      during excessive illumination by transmission electron microscopy (TEM) and
      immunogold labeling of FtsH. The change in distribution of the protease was
      accompanied by structural changes to the thylakoids, which we detected using
      spinach leaves by TEM after chemical fixation of the samples. Quantitative
      analyses showed several characteristic changes in the structure of the
      thylakoids, including shrinkage of the grana, outward bending of the marginal
      portions of the thylakoids and an increase in the height of the grana stacks
      under excessive illumination. The increase in the height of the grana stacks may
      include swelling of the thylakoids and an increase in the partition gaps between
      the thylakoids. These data strongly suggest that excessive illumination induces
      partial unstacking of the thylakoids, which enables FtsH to access easily the
      photodamaged D1 protein. Finally three-dimensional tomography of the grana was
      recorded to observe the effect of light stress on the overall structure of the
      thylakoids. 

PMID- 24891561
TI  - Enhanced heterotetrameric assembly of potato ADP-glucose pyrophosphorylase using
      reverse genetics.
AB  - ADP-glucose pyrophosphorylase (AGPase) is a key allosteric enzyme in plant starch
      biosynthesis. Plant AGPase is a heterotetrameric enzyme that consists of large
      (LS) and small subunits (SS), which are encoded by two different genes.
      Computational and experimental studies have revealed that the heterotetrameric
      assembly of AGPase is thermodynamically weak. Modeling studies followed by the
      mutagenesis of the LS of the potato AGPase identified a heterotetramer-deficient
      mutant, LS(R88A). To enhance heterotetrameric assembly, LS(R88A) cDNA was
      subjected to error-prone PCR, and second-site revertants were identified
      according to their ability to restore glycogen accumulation, as assessed with
      iodine staining. Selected mutations were introduced into the wild-type (WT) LS
      and co-expressed with the WT SS in Escherichia coli glgC(-). The biochemical
      characterization of revertants revealed that LS(I90V)SS(WT), LS(Y378C)SS(WT) and
      LS(D410G)SS(WT) mutants displayed enhanced heterotetrameric assembly with the WT
      SS. Among these mutants, LS(Y378C)SS(WT) AGPase displayed increased heat
      stability compared with the WT enzyme. Kinetic characterization of the mutants
      indicated that the LS(I90V)SS(WT) and LS(Y378C)SS(WT) AGPases have comparable
      allosteric and kinetic properties. However, the LS(D410G)SS(WT) mutant exhibited
      altered allosteric properties of being less responsive and more sensitive to 3
      phosphoglyceric acid activation and inorganic phosphate inhibition. This study
      not only enhances our understanding of the interaction between the SS and the LS
      of AGPase but also enables protein engineering to obtain enhanced assembled heat
      stable variants of AGPase, which can be used for the improvement of plant yields.

PMID- 24891562
TI  - The role of relationship biography in advance care planning.
AB  - OBJECTIVE: We examine the ways that romantic relationship biographies are related
      to whether, how, and with whom individuals complete advance care planning (ACP),
      preparations for end-of-life medical care. METHOD: Data are from an Internet
      survey of 2,144 adults aged 18 to 64, all of whom were either married to or
      cohabiting with an opposite-sex partner. RESULTS: Cohabitors were less likely
      than married people to complete ACP. Relationship quality was an important
      influence on ACP, but did not account for the differences between married and
      cohabiting persons. Differences were largely explained by the age composition of
      the groups. DISCUSSION: Couples who foresee a long and stable future together are
      those most likely to engage in end-of-life planning, a preventative health
      behavior with long-term consequences for well-being.

PMID- 24891564
TI  - Veteran status and men's later-life cognitive trajectories: evidence from the
      health and retirement study.
AB  - OBJECTIVE: The aim of this study is to determine the extent to which men's later
      life cognitive trajectories vary by veteran status. METHOD: We use Health and
      Retirement Study (HRS) data to estimate growth curve models examining men's later
      life cognitive trajectories by veteran status, war service status, and period of
      service. Analyses control for early-life characteristics that influence selection
      into military service and later-life cognition, and mid- to late-life
      characteristics that potentially mediate the relationship between military
      service and later-life cognition. RESULTS: Veterans have higher cognition scores
      relative to nonveterans around retirement age, but their cognition scores decline
      more rapidly with increasing age, such that cognition scores are similar in both
      groups among the oldest old. Veterans who served during the Korean War have lower
      cognition scores around retirement age, but less steep age-related declines, than
      veterans who served during World War II. DISCUSSION: Findings are discussed in
      relation to the extant literature, future research, potential service needs, and
      study limitations.

PMID- 24891563
TI  - Increases in blood glucose in older adults: the effects of spousal health.
AB  - OBJECTIVE: The death or illness of a spouse negatively affects a partner's
      health, but little is known about the effect on blood glucose (glycemic) levels.
      This study investigates the extent to which a spouse's declining health or death
      is associated with changes in the glycemic levels of older adults. METHOD: Data
      come from a nationally representative longitudinal sample of 597 Taiwanese (aged
      54 to 90). We use changes in spousal health and death of a spouse to predict
      changes in glycosylated hemoglobin (HbA1c) levels over a 6-year period. RESULTS:
      A decline in spousal health is associated with increased HbA1c levels for women,
      but not for men. The death of a healthy spouse is associated with increased HbA1c
      levels for both genders. DISCUSSION: Stressful life transitions may compromise
      the glycemic levels of older adults. Taking on a caregiving role may erode some
      of the benefits of marriage and interfere with women's maintenance of their own
      health.

PMID- 24891565
TI  - Social stratification, oral hygiene, and trajectories of dental caries among old
      Americans.
AB  - OBJECTIVE: This study analyzed how oral hygiene (i.e., brushing, rinsing, and
      flossing) influences the trajectories of dental caries (i.e., numbers of decayed,
      missing, and filled teeth) among older Americans within the context of social
      stratification. METHOD: Data came from Piedmont Dental Study that involved a
      sample of 810 older Americans who were dentate in 1988 with up to four repeated
      observations through 1994. Hierarchical linear models were used for data
      analysis. RESULTS: Brushing, flossing, and rinsing were associated with the
      trajectories of dental caries in distinct ways. In addition, oral hygiene was
      correlated with race, education, household income, and use of dental care. The
      effects of brushing and flossing on decayed and missing teeth remained robust,
      even when socio-demographic and health attributes were controlled. Conversely,
      socioeconomic disparities in dental caries persisted, when oral hygiene was
      adjusted. DISCUSSION: Both social stratification and oral hygiene need to be
      considered in promoting oral health.

PMID- 24891566
TI  - Editorial: Have we reached the era of the bespoke anterior cruciate ligament
      reconstruction?

PMID- 24891567
TI  - Periprosthetic fractures associated with joint replacement: our Tower of Babel?

PMID- 24891568
TI  - The Unified Classification System (UCS): improving our understanding of
      periprosthetic fractures.
AB  - Periprosthetic fractures are an increasingly common complication following joint
      replacement. The principles which underpin their evaluation and treatment are
      common across the musculoskeletal system. The Unified Classification System
      proposes a rational approach to treatment, regardless of the bone that is broken
      or the joint involved.

PMID- 24891569
TI  - Back pain in children and adolescents.
AB  - Back pain is a common symptom in children and adolescents. Here we review the
      important causes, of which defects and stress reactions of the pars
      interarticularis are the most common identifiable problems. More serious
      pathology, including malignancy and infection, needs to be excluded when there is
      associated systemic illness. Clinical evaluation and management may be difficult
      and always requires a thorough history and physical examination. Diagnostic
      imaging is obtained when symptoms are persistent or severe. Imaging is used to
      reassure the patient, relatives and carers, and to guide management.

PMID- 24891570
TI  - The frequency of sequelae of slipped upper femoral epiphysis in cam-type
      femoroacetabular impingement.
AB  - Slipped upper femoral epiphysis (SUFE) is one of the known causes of cam-type
      femoroacetabular impingement (FAI). The aim of this study was to determine the
      proportion of FAI cases considered to be secondary to SUFE-like deformities. We
      performed a case-control study on 96 hips (75 patients: mean age 38 years (15.4
      to 63.5)) that had been surgically treated for FAI between July 2005 and May
      2011. Three independent observers measured the lateral view head-neck index
      (LVHNI) to detect any SUFE-like deformity on lateral hip radiographs taken in 45
      degrees  flexion, 45 degrees  abduction and 30 degrees  external rotation. A
      control group of 108 healthy hips in 54 patients was included for comparison
      (mean age 36.5 years (24.3 to 53.9). The impingement group had a mean LVHNI of
      7.6% (16.7% to -2%) versus 3.2% in the control group (10.8% to -3%) (p < 0.001).
      A total of 42 hips (43.7%) had an index value > 9% in the impingement group
      versus only six hips (5.5%) in the control group (p < 0.001). The impingement
      group had a mean alpha angle of 73.9 degrees  (96.2 degrees  to 53.4 degrees )
      versus 48.2 degrees  (65 degrees  to 37 degrees ) in the control group (p <
      0.001). Our results suggest that SUFE is one of the primary aetiological factors
      for cam-type FAI.

PMID- 24891571
TI  - The S-ROM hydroxyapatite proximally-coated modular femoral stem in revision hip
      replacement: results of 397 hips at a minimum ten-year follow-up.
AB  - We report on 397 consecutive revision total hip replacements in 371 patients with
      a mean clinical and radiological follow-up of 12.9 years (10 to 17.7). The mean
      age at surgery was 69 years (37 to 93). A total of 28 patients (8%) underwent
      further revision, including 16 (4%) femoral components. In all 223 patients (56%,
      233 hips) died without further revision and 20 patients (5%, 20 hips) were lost
      to follow-up. Of the remaining patients, 209 (221 hips) were available for
      clinical assessment and 194 (205 hips) for radiological review at mean follow-up
      of 12.9 years (10 to 17.7). The mean Harris Hip Score improved from 58.7 (11 to
      92) points to 80.7 (21 to 100) (p < 0.001) and the mean Merle d'Aubigne and
      Postel hip scores at final follow-up were 4.9 (2 to 6), 4.5 (2 to 6) and 4.3 (2
      to 6), respectively for pain, mobility and function. Radiographs showed no
      lucencies around 186 (90.7%) femoral stems with stable bony ingrowth seen in 199
      stems (97%). The survival of the S-ROM femoral stem at 15 years with revision for
      any reason as the endpoint was 90.5% (95% confidence interval (CI) 85.7 to 93.8)
      and with revision for aseptic loosening as the endpoint 99.3% (95% CI 97.2 to
      99.8). We have shown excellent long-term survivorship and good clinical outcome
      of a cementless hydroxyapatite proximally-coated modular femoral stem in revision
      hip surgery.

PMID- 24891572
TI  - Knee shape might predict clinical outcome after an anterior cruciate ligament
      rupture.
AB  - We have investigated whether shape of the knee can predict the clinical outcome
      of patients after an anterior cruciate ligament rupture. We used statistical
      shape modelling to measure the shape of the knee joint of 182 prospectively
      followed patients on lateral and Rosenberg view radiographs of the knee after a
      rupture of the anterior cruciate ligament. Subsequently, we associated knee shape
      with the International Knee Documentation Committee subjective score at two years
      follow-up. The mean age of patients was 31 years (21 to 51), the majority were
      male (n = 121) and treated operatively (n = 135). We found two modes (shape
      variations) that were significantly associated with the subjective score at two
      years: one for the operatively treated group (p = 0.002) and one for the non
      operatively treated group (p = 0.003). Operatively treated patients who had
      higher subjective scores had a smaller intercondylar notch and a smaller width of
      the intercondylar eminence. Non-operatively treated patients who scored higher on
      the subjective score had a more pyramidal intercondylar notch as opposed to one
      that was more dome-shaped. We conclude that the shape of the femoral notch and
      the intercondylar eminence is predictive of clinical outcome two years after a
      rupture of the anterior cruciate ligament.

PMID- 24891573
TI  - Graft-bending angle and femoral tunnel length after single-bundle anterior
      cruciate ligament reconstruction: comparison of the transtibial, anteromedial
      portal and outside-in techniques.
AB  - We used immediate post-operative in vivo three-dimensional computed tomography to
      compare graft bending angles and femoral tunnel lengths in 155 patients who had
      undergone single-bundle reconstruction of the anterior cruciate ligament using
      the transtibial (n = 37), anteromedial portal (n = 72) and outside-in (n = 46)
      techniques. The bending angles in the sagittal and axial planes were
      significantly greater but the coronal-bending angle was significantly less in the
      transtibial group than in the anteromedial portal and outside-in groups (p <
      0.001 each). The mean length of the femoral tunnel in all three planes was
      significantly greater in the transtibial group than the anteromedial portal and
      outside-in groups (p < 0.001 each), but all mean tunnel lengths in the three
      groups exceeded 30 mm. The only significant difference was the coronal graft-
      bending angle in the anteromedial portal and outside-in groups (23.5 degrees  vs
      29.8 degrees , p = 0.012). Compared with the transtibial technique, the
      anteromedial portal and outside-in techniques may reduce the graft-bending stress
      at the opening of the femoral tunnel. Despite the femoral tunnel length being
      shorter in the anteromedial portal and outside-in techniques than in the
      transtibial technique, a femoral tunnel length of more than 30 mm in the
      anteromedial portal and outside-in techniques may be sufficient for the graft to
      heal.

PMID- 24891574
TI  - Staged bilateral total knee replacement: changes in expectations and outcomes
      between the first and second operations.
AB  - We explored the outcome of staged bilateral total knee replacement (TKR) for
      symmetrical degenerative joint disease and deformity in terms of patient
      expectations, functional outcome and satisfaction. From 2009 to 2011, 70
      consecutive patients (41 female) with a mean age of 71.7 years (43 to 89)
      underwent 140 staged bilateral TKRs at our institution, with a mean time between
      operations of 7.8 months (2 to 25). Patients were assessed pre-operatively and at
      six and 12 months post-operatively using the Short Form-12, Oxford knee score
      (OKS), expectation questionnaire and satisfaction score. The pre-operative OKS
      was significantly worse before the first TKR (TKR1), but displayed significantly
      greater improvement than that observed after the second TKR (TKR2). Expectation
      level increased from TKR1 to TKR2 in 17% and decreased in 20%. Expectations of
      pain relief and stair-climbing were less before TKR2; in contrast, expectations
      of sporting and social activities were greater. Decreased expectations of TKR2
      were significantly associated with younger age and high expectations before TKR1.
      Patient satisfaction was high for both TKR1 (93%) and TKR2 (87%) but did not
      correlate significantly within individuals. We concluded that satisfaction with
      one TKR does not necessarily translate to satisfaction following the second.

PMID- 24891576
TI  - Autologous wound drains have no effect on allogeneic blood transfusions in
      primary total hip and knee replacement: a three-arm randomised trial.
AB  - We hypothesised there was no clinical value in using an autologous blood
      transfusion (ABT) drain in either primary total hip (THR) or total knee
      replacement (TKR) in terms of limiting allogeneic blood transfusions when a
      modern restrictive blood management regime was followed. A total of 575 patients
      (65.2% men), with a mean age of 68.9 years (36 to 94) were randomised in this
      three-arm study to no drainage (group A), or to wound drainage with an ABT drain
      for either six hours (group B) or 24 hours (group C). The primary outcome was the
      number of patients receiving allogeneic blood transfusion. Secondary outcomes
      were post-operative haemoglobin (Hb) levels, length of hospital stay and adverse
      events. This study identified only 41 transfused patients, with no significant
      difference in distribution between the three groups (p = 0.857). The mean pre
      operative haemoglobin (Hb) value in the transfused group was 12.8 g/dL (9.8 to
      15.5) versus 14.3 g/dL (10.6 to 18.0) in the non-transfused group (p < 0.001, 95%
      confidence interval: 1.08 to 1.86). Post-operatively, the median of re-transfused
      shed blood in patients with a THR was 280 mL (Interquartile range (IQR) 150 to
      400) and in TKR patients 500 mL (IQR 350 to 650) (p < 0.001). ABT drains had no
      effect on the proportion of transfused patients in primary THR and TKR. The
      secondary outcomes were also comparable between groups.

PMID- 24891575
TI  - Single-stage revision for the infected total knee replacement: results from a
      single centre.
AB  - Peri-prosthetic infection is amongst the most common causes of failure following
      total knee replacement (TKR). In the presence of established infection, thorough
      joint debridement and removal of all components is necessary following which new
      components may be implanted. This can be performed in one or two stages; two
      stage revision with placement of an interim antibiotic-loaded spacer is regarded
      by many to be the standard procedure for eradication of peri-prosthetic joint
      infection. We present our experience of a consecutive series of 50 single-stage
      revision TKRs for established deep infection performed between 1979 and 2010.
      There were 33 women and 17 men with a mean age at revision of 66.8 years (42 to
      84) and a mean follow-up of 10.5 years (2 to 24). The mean time between the
      primary TKR and the revision procedure was 2.05 years (1 to 8). Only one patient
      required a further revision for recurrent infection, representing a success rate
      of 98%. Nine patients required further revision for aseptic loosening, according
      to microbiological testing of biopsies taken at the subsequent surgery. Three
      other patients developed a further septic episode but none required another
      revision. These results suggest that a single-stage revision can produce
      comparable results to a two-stage revision. Single-stage revision offers a
      reduction in costs as well as less morbidity and inconvenience for patients.

PMID- 24891577
TI  - The treatment and outcome of peri-prosthetic infection of the ankle: a single
      cohort-centre experience of 34 cases.
AB  - The treatment of peri-prosthetic joint infection (PJI) of the ankle is not
      standardised. It is not clear whether an algorithm developed for hip and knee PJI
      can be used in the management of PJI of the ankle. We evaluated the outcome, at
      two or more years post-operatively, in 34 patients with PJI of the ankle,
      identified from a cohort of 511 patients who had undergone total ankle
      replacement. Their median age was 62.1 years (53.3 to 68.2), and 20 patients were
      women. Infection was exogenous in 28 (82.4%) and haematogenous in six (17.6%); 19
      (55.9%) were acute infections and 15 (44.1%) chronic. Staphylococci were the
      cause of 24 infections (70.6%). Surgery with retention of one or both components
      was undertaken in 21 patients (61.8%), both components were replaced in ten
      (29.4%), and arthrodesis was undertaken in three (8.8%). An infection-free
      outcome with satisfactory function of the ankle was obtained in 23 patients
      (67.6%). The best rate of cure followed the exchange of both components (9/10,
      90%). In the 21 patients in whom one or both components were retained, four had a
      relapse of the same infecting organism and three had an infection with another
      organism. Hence the rate of cure was 66.7% (14 of 21). In these 21 patients, we
      compared the treatment given to an algorithm developed for the treatment of PJI
      of the knee and hip. In 17 (80.9%) patients, treatment was not according to the
      algorithm. Most (11 of 17) had only one criterion against retention of one or
      both components. In all, ten of 11 patients with severe soft-tissue compromise as
      a single criterion had a relapse-free survival. We propose that the treatment
      concept for PJI of the ankle requires adaptation of the grading of quality of the
      soft tissues.

PMID- 24891578
TI  - Gastrocsoleus recession techniques: an anatomical and biomechanical study in
      human cadavers.
AB  - Lengthening of the conjoined tendon of the gastrocnemius aponeurosis and soleus
      fascia is frequently used in the treatment of equinus deformities in children and
      adults. The Vulpius procedure as described in most orthopaedic texts is a
      division of the conjoined tendon in the shape of an inverted V. However,
      transverse division was also described by Vulpius and Stoffel, and has been
      reported in some clinical studies. We studied the anatomy and biomechanics of
      transverse division of the conjoined tendon in 12 human cadavers (24 legs).
      Transverse division of the conjoined tendon resulted in predictable, controlled
      lengthening of the gastrocsoleus muscle-tendon unit. The lengthening achieved was
      dependent both on the level of the cut in the conjoined tendon and division of
      the midline raphe. Division at a proximal level resulted in a mean lengthening of
      15.2 mm (sd 2.0, (12 to 19), which increased to 17.1 mm (sd 1.8, (14 to 20) after
      division of the midline raphe. Division at a distal level resulted in a mean
      lengthening of 21.0 mm (sd 2.0, (18 to 25), which increased to 26.4 mm (sd 1.4,
      (24 to 29) after division of the raphe. These differences were significant (p <
      0.001).

PMID- 24891579
TI  - The treatment of intramedullary osteomyelitis of the femur and tibia using the
      Reamer-Irrigator-Aspirator system and antibiotic cement rods.
AB  - Intramedullary infection in long bones represents a complex clinical challenge,
      with an increasing incidence due to the increasing use of intramedullary
      fixation. We report a prospective case series using an intramedullary reaming
      device, the Reamer-Irrigator-Aspirator (RIA) system, in association with
      antibiotic cement rods for the treatment of lower limb long bone infections. A
      total of 24 such patients, 16 men and eight women, with a mean age of 44.5 years
      (17 to 75), 14 with femoral and 10 with tibial infection, were treated in a
      staged manner over a period of 2.5 years in a single referral centre. Of these,
      21 patients had had previous surgery, usually for fixation of a fracture (seven
      had sustained an open fracture originally and one had undergone fasciotomies).
      According to the Cierny-Mader classification system, 18 patients were classified
      as type 1A, four as 3A (discharging sinus tract), one as type 4A and one as type
      1B. Staphylococcus species were isolated in 20 patients (83.3%). Local antibiotic
      delivery was used in the form of impregnated cement rods in 23 patients. These
      were removed at a mean of 2.6 months (1 to 5). Pathogen-specific antibiotics were
      administered systemically for a mean of six weeks (3 to 18). At a mean follow-up
      of 21 months (8 to 36), 23 patients (96%) had no evidence of recurrent infection.
      One underwent a planned trans-tibial amputation two weeks post-operatively due to
      peripheral vascular disease and chronic recalcitrant osteomyelitis of the tibia
      and foot. The combination of RIA reaming, the administration of systemic pathogen
      specific antibiotics and local delivery using impregnated cement rods proved to
      be a safe and efficient form of treatment in these patients.

PMID- 24891580
TI  - An anatomical study of transfer of the anterior interosseous nerve for the
      treatment of proximal ulnar nerve injuries.
AB  - We conducted an anatomical study to determine the best technique for transfer of
      the anterior interosseous nerve (AIN) for the treatment of proximal ulnar nerve
      injuries. The AIN, ulnar nerve, and associated branches were dissected in 24
      cadaver arms. The number of branches of the AIN and length available for transfer
      were measured. The nerve was divided just proximal to its termination in pronator
      quadratus and transferred to the ulnar nerve through the shortest available
      route. Separation of the deep and superficial branches of the ulnar nerve by
      blunt dissection alone, was also assessed. The mean number of AIN branches was
      4.8 (3 to 8) and the mean length of the nerve available for transfer was 72 mm
      (41 to 106). The transferred nerve reached the ulnar nerve most distally when
      placed dorsal to flexor digitorum profundus (FDP). We therefore conclude that the
      AIN should be passed dorsal to FDP, and that the deep and superficial branches of
      the ulnar nerve require approximately 30 mm of blunt dissection and 20 mm of
      sharp dissection from the point of bifurcation to the site of the anastomosis.
      The use of this technique for transfer of the AIN should improve the outcome for
      patients with proximal ulnar nerve injuries.

PMID- 24891581
TI  - Ultrasound-guided supraclavicular brachial plexus block in upper limb surgery:
      outcomes and patient satisfaction.
AB  - We examined the outcomes and levels of patient satisfaction in 202 consecutive
      cases of ultrasound-guided supraclavicular brachial plexus block (SBPB) in upper
      limb surgery performed between September 2007 and March 2010. All blocks were
      performed by orthopaedic surgeons using ultrasound visualisation with a high
      frequency linear probe. The probe was placed in the coronal-oblique plane in the
      supraclavicular fossa, and the puncture was 'in-plane' from lateral to medial.
      Most of the blocks were performed with 0.75% ropivacaine/1% lidocaine (1:1), with
      or without adrenaline in 1:200 000 dilution. In 201 patients (99.5%) the brachial
      plexus block permitted surgery without conversion to general anaesthesia. The
      mean procedure time for block was 3.9 min (2 to 12), the mean waiting time for
      surgery was 34.1 min (10 to 64), the mean surgical time was 75.2 min (6 to 232),
      and the mean duration of post-anaesthetic analgesia was 437 min (171 to 992). A
      total of 20 patients (10%) developed a transient Horner's syndrome. No nerve
      injury, pneumothorax, arterial puncture or systemic anaesthetic toxicity were
      recorded. Most patients (96.7%) were satisfied with ultrasound-guided SBPB. This
      study demonstrates the efficacy and safety of ultrasound-guided SBPB for
      orthopaedic surgery on the upper limb.

PMID- 24891582
TI  - The surgical treatment of lordoscoliosis and hyperlordosis in patients with
      quadriplegic cerebral palsy.
AB  - We describe 13 patients with cerebral palsy and lordoscoliosis/hyperlordosis of
      the lumbar spine who underwent a posterior spinal fusion at a mean age of 14.5
      years (10.8 to 17.4) to improve sitting posture and relieve pain. The mean follow
      up was 3.3 years (2.2 to 6.2). The mean pre-operative lumbar lordosis was 108(
      degrees ) (80 to 150( degrees )) and was corrected to 62( degrees ) (43( degrees
      ) to 85( degrees )); the mean thoracic kyphosis from 17( degrees ) (-23( degrees
      ) to 35( degrees )) to 47( degrees ) (25( degrees ) to 65( degrees )); the mean
      scoliosis from 82( degrees ) (0( degrees ) to 125( degrees )) to 22( degrees )
      (0( degrees ) to 40( degrees )); the mean pelvic obliquity from 21( degrees ) (0(
      degrees ) to 38( degrees )) to 3( degrees ) (0( degrees ) to 15( degrees )); the
      mean sacral slope from 79( degrees ) (54( degrees ) to 90( degrees )) to 50(
      degrees ) (31( degrees ) to 66( degrees )). The mean pre-operative coronal
      imbalance was 5 cm (0 cm to 8.9 cm) and was corrected to 0.6 cm (0 to 3.2). The
      mean sagittal imbalance of -8 cm (-16 cm to 7.8 cm) was corrected to -1.6 cm (-4
      cm to 2.5 cm). The mean operating time was 250 minutes (180 to 360 minutes) and
      intra-operative blood loss 0.8 of estimated blood volume (0.3 to 2 estimated
      blood volume). The mean intensive care and hospital stay were 3.5 days (2 to 8)
      and 14.5 days (10 to 27), respectively. Three patients lost a significant amount
      of blood intra-operatively and subsequently developed chest or urinary infections
      and superior mesenteric artery syndrome. An increased pre-operative lumbar
      lordosis and sacral slope were associated with increased peri-operative
      morbidity: scoliosis and pelvic obliquity were not. A reduced lumbar lordosis and
      increased thoracic kyphosis correlated with better global sagittal balance at
      follow-up. All patients and their parents reported excellent surgical outcomes.
      Lordoscoliosis and hyperlordosis are associated with significant morbidity in
      quadriplegic patients. They are rare deformities and their treatment is
      challenging. Sagittal imbalance is the major component: it can be corrected by
      posterior fusion of the spine with excellent functional results.

PMID- 24891583
TI  - National trends in revision spinal fusion in the USA: patient characteristics and
      complications.
AB  - Using the United States Nationwide Inpatient Sample, we identified national
      trends in revision spinal fusion along with a comprehensive comparison of
      comorbidities, inpatient complications and surgical factors of revision spinal
      fusion compared to primary spinal fusion. In 2009, there were 410 158 primary
      spinal fusion discharges and 22 128 revision spinal fusion discharges. Between
      2002 and 2009, primary fusion increased at a higher rate compared with revision
      fusion (56.4% vs 51.0%; p < 0.001). In 2009, the mean length of stay and hospital
      charges were higher for revision fusion discharges than for primary fusion
      discharges (4.2 days vs 3.8 days, p < 0.001; USD $91 909 vs. $87 161, p < 0.001).
      In 2009, recombinant human bone morphogenetic protein (BMP) was used more in
      revision fusion than in primary fusion (39.6% vs 27.6%, p < 0.001), whereas
      interbody devices were used less in revision fusion (41.8% vs 56.6%, p < 0.001).
      In the multivariable logistic regression model for all spinal fusions, depression
      (odds ratio (OR) 1.53, p < 0.001), psychotic disorders (OR 1.49, p < 0.001),
      deficiency anaemias (OR 1.35, p < 0.001) and smoking (OR 1.10, p = 0.006) had a
      greater chance of occurrence in revision spinal fusion discharges than in primary
      fusion discharges, adjusting for other variables. In terms of complications,
      after adjusting for all significant comorbidities, this study found that dural
      tears (OR 1.41; p < 0.001) and surgical site infections (OR 3.40; p < 0.001) had
      a greater chance of occurrence in revision spinal fusion discharges than in
      primary fusion discharges (p < 0.001). A p-value < 0.01 was considered
      significant in all final analyses.

PMID- 24891584
TI  - Fragility fractures of the ankle in the frail elderly patient: treatment with a
      long calcaneotalotibial nail.
AB  - Conventional methods of treating ankle fractures in the elderly are associated
      with high rates of complication. We describe the results of treating these
      injuries in 48 frail elderly patients with a long calcaneotalotibial nail. The
      mean age of the group was 82 years (61 to 96) and 41 (85%) were women. All were
      frail, with multiple medical comorbidities and their mean American Society of
      Anaesthesiologists score was 3 (3 to 4). None could walk independently before
      their operation. All the fractures were displaced and unstable; the majority
      (94%, 45 of 48) were low-energy injuries and 40% (19 of 48) were open. The
      overall mortality at six months was 35%. Of the surviving patients, 90% returned
      to their pre-injury level of function. The mean pre- and post-operative Olerud
      and Molander questionnaire scores were 62 and 57 respectively. Complications
      included superficial infection (4%, two of 48); deep infection (2%, one of 48); a
      broken or loose distal locking screw (6%, three of 48); valgus malunion (4%, two
      of 48); and one below-knee amputation following an unsuccessful vascular
      operation. There were no cases of nonunion, nail breakage or peri-prosthetic
      fracture. A calcaneotalotibial nail is an excellent device for treating an
      unstable fracture of the ankle in the frail elderly patient. It allows the
      patient to mobilise immediately and minimises the risk of bone or wound problems.
      A long nail which crosses the isthmus of the tibia avoids the risk of peri
      prosthetic fracture associated with shorter devices.

PMID- 24891585
TI  - The presentation, treatment and outcome of periosteal chondrosarcoma in the
      Netherlands.
AB  - In this case study, we describe the clinical presentation and treatment of 36
      patients with periosteal chondrosarcoma collected over a 59-year period by the
      archive of the Netherlands Committee on Bone Tumours. The demographics, clinical
      presentation, radiological features, treatment and follow-up are presented with
      the size, location, the histological grading of the tumour and the survival. We
      found a slight predominance of men (61%), and a predilection for the distal femur
      (33%) and proximal humerus (33%). The metaphysis was the most common site (47%)
      and the most common presentation was with pain (44%). Half the tumours were
      classified histologically as grade 1. Pulmonary metastases were reported in one
      patient after an intra-lesional resection. A second patient died from local
      recurrence and possible pulmonary and skin metastases after an incomplete
      resection. It is clearly important to make the diagnosis appropriately because an
      incomplete resection may result in local recurrence and metastatic spread.
      Staging for metastatic disease is recommended in grade II or III lesions. These
      patients should be managed with a contrast-enhanced MRI of the tumour and
      histological confirmation by biopsy, followed by en-bloc excision.

PMID- 24891586
TI  - The use of a biodegradable antibiotic-loaded calcium sulphate carrier containing
      tobramycin for the treatment of chronic osteomyelitis: a series of 195 cases.
AB  - We report our experience using a biodegradable calcium sulphate antibiotic
      carrier containing tobramycin in the surgical management of patients with chronic
      osteomyelitis. The patients were reviewed to determine the rate of recurrent
      infection, the filling of bony defects, and any problems with wound healing. A
      total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0)
      underwent surgery. According to the Cierny-Mader classification of osteomyelitis
      there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean
      follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18
      cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further
      treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze
      (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which
      there were no recurrent infection. Radiographic assessment at final follow-up
      showed no filling of the defect with bone in 67 (36.6%), partial filling in 108
      (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%)
      of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after
      operation. We conclude that Osteoset T is helpful in the management of patients
      with chronic osteomyelitis, but the filling of the defect in bone is variable.
      Prolonged wound ooze is usually self-limiting and not associated with recurrent
      infection.

PMID- 24891587
TI  - The surgical treatment of children with congenital convex foot (vertical talus):
      evaluation of midtarsal surgical release and open reduction.
AB  - In this study we evaluated the results of midtarsal release and open reduction
      for the treatment of children with convex congenital foot (CCF) (vertical talus)
      and compared them with the published results of peritalar release. Between 1977
      and 2009, a total of 22 children (31 feet) underwent this procedure. In 15
      children (48%) the CCF was isolated and in the remainder it was not (seven with
      arthrogryposis, two with spinal dysraphism, one with a polymalformative syndrome
      and six with an undefined neurological disorder). Pre-operatively, the mean
      tibiotalar angle was 150.2 degrees  (106 degrees  to 175 degrees ) and the mean
      calcaneal pitch angle was -19.3 degrees  (-72 degrees  to 4 degrees ). The
      procedure included talonavicular and calcaneocuboid joint capsulotomies,
      lengthening of tendons of tibialis anterior and the extensors of the toes,
      allowing reduction of the midtarsal joints. Lengthening of the Achilles tendon
      was necessary in 23 feet (74%). The mean follow-up was 11 years (2 to 21). The
      results, as assessed by the Adelaar score, were good in 24 feet (77.4%), fair in
      six (19.3%) and poor in one foot (3.3%), with no difference between those with
      isolated CCF and those without. The mean American Orthopaedic Foot and Ankle
      Society midfoot score was 89.9 (54 to 100) and 77.8 (36 to 93) for those with
      isolated CCF and those without, respectively. At the final follow-up, the mean
      tibiotalar (120 degrees ; 90 to 152) and calcaneal pitch angles (4 degrees ; -13
      to 22) had improved significantly (p < 0.0001). Dislocation of the talonavicular
      and calcaneocuboid joints was completely reduced in 22 (70.9%) and 29 (93.6%) of
      feet, respectively. Three children (five feet) underwent further surgery at a
      mean of 8.5 years post-operatively, three with pes planovalgus and two in whom
      the deformity had been undercorrected. No child developed avascular necrosis of
      the talus. Midtarsal joint release and open reduction is a satisfactory
      procedure, which may provide better results than peritalar release. Complications
      include the development of pes planovalgus and persistent dorsal subluxation of
      the talonavicular joint.

PMID- 24891590
TI  - Sea change in open science and data sharing: leadership by industry.

PMID- 24891588
TI  - A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded
      calcium-based bone substitutes in the treatment of chronic osteomyelitis: a
      retrospective comparative study.
AB  - The treatment of chronic osteomyelitis often includes surgical debridement and
      filling the resultant void with antibiotic-loaded polymethylmethacrylate cement,
      bone grafts or bone substitutes. Recently, the use of bioactive glass to treat
      bone defects in infections has been reported in a limited series of patients.
      However, no direct comparison between this biomaterial and antibiotic-loaded bone
      substitute has been performed. In this retrospective study, we compared the
      safety and efficacy of surgical debridement and local application of the
      bioactive glass S53P4 in a series of 27 patients affected by chronic
      osteomyelitis of the long bones (Group A) with two other series, treated
      respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate
      compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic
      loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were
      also used in all groups. After comparable periods of follow-up, the control of
      infection was similar in the three groups. In particular, 25 out of 27 (92.6%)
      patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in
      Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to
      36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a
      reduced wound complication rate. Our results show that patients treated with a
      bioactive glass without local antibiotics achieved similar eradication of
      infection and less drainage than those treated with two different antibiotic
      loaded calcium-based bone substitutes.

PMID- 24891591
TI  - Lots of planets have a North...

PMID- 24891595
TI  - Influenza and parainfluenza viral infections in children.
AB  - * On the basis of strong epidemiologic evidence, influenza and parainfluenza
      viruses are responsible for significant morbidity and mortality in young infants
      and children and in persons with chronic medical conditions. (1)(4)(26)(27)(35).
      * On the basis of research evidence, influenza vaccines are effective in
      preventing disease in high-risk individuals. (8)(17)(18). * On the basis of
      strong research evidence, influenza vaccines are safe in young infants and
      children 6 months or older. (8)(15).* On the basis of research evidence, the use
      of corticosteroids and epinephrine is beneficial in the treatment of
      laryngotracheitis caused by parainfluenza viruses. (44)(45)(46)(47). * Strong
      evidence supports the use of influenza vaccines in pregnant mothers as a strategy
      to prevent disease in infants younger than 6 months. (17)(18)(19).

PMID- 24891593
TI  - Preventive Services by Medical and Dental Providers and Treatment Outcomes.
AB  - OBJECTIVE: Nearly all state Medicaid programs reimburse nondental primary care
      providers (PCPs) for providing preventive oral health services to young children;
      yet, little is known about how treatment outcomes compare with children visiting
      dentists. This study compared the association between the provider of preventive
      services (PCP, dentist, or both) with Medicaid-enrolled children before their
      third birthday and subsequent dental caries-related treatment (CRT) and CRT
      payment. METHODS: We conducted a retrospective study of young children enrolled
      in North Carolina Medicaid during 2000 to 2006. The annual number of CRT and CRT
      payments per child between the ages of 3 and 5 yr were estimated with a zero
      inflated negative binomial regression and a hurdle model, respectively. Models
      were adjusted for relevant child- and county-level characteristics and used
      propensity score weighting to address observed confounding. RESULTS: We examined
      41,453 children with > 1 preventive oral health visit from a PCP, dentist, or
      both before their third birthday. Unadjusted annual mean CRT and payments were
      lowest among children who had only PCP visits (CRT = 0.87, payment = $172) and
      higher among children with only dentist visits (CRT = 1.48, payment = $234) and
      both PCP and dentist visits (CRT = 1.52, payment = $273). Adjusted results
      indicated that children who had dentist visits (with or without PCP visits) had
      significantly more CRT and higher CRT payments per year during the ages of 3 and
      4 yr than children who had only PCP visits. However, these differences attenuated
      each year after age 3 yr. CONCLUSIONS: Because of children's increased
      opportunity to receive multiple visits in medical offices during well-child
      visits, preventive oral health services provided by PCPs may lead to a greater
      reduction in CRT than dentist visits alone. This study supports guidelines and
      reimbursement policies that allow preventive dental visits based on individual
      needs.

PMID- 24891594
TI  - Characterization of a novel recombinant hyaluronan binding protein for tissue
      hyaluronan detection.
AB  - Tumor necrosis factor-Stimulated Gene 6 protein (TSG-6) is a hyaluronan (HA)
      binding glycoprotein containing an HA-binding Link module. Because of its well
      defined structure, HA binding properties and small size, TSG-6 is an excellent
      candidate as an alternative to animal-derived HA-binding protein (HABP) for the
      detection of HA. The present work describes the generation and characterization
      of a novel recombinant HA-binding probe obtained by fusion of a modified TSG-6
      Link module with mutationally inactivated heparin-binding sequence and the Fc
      portion of human IgG1 (TSG-6-DeltaHep-Fc) for tissue HA detection in histological
      samples. Direct binding assays indicated strong binding of TSG-6-DeltaHep-Fc to
      HA, with little residual binding to heparin. Histolocalization of HA in formalin
      fixed, paraffin-embedded tissue sections using biotin-TSG-6-DeltaHep-Fc resulted
      in hyaluronidase-sensitive staining patterns similar to those obtained with
      biotin-HABP, but with improved sensitivity. HA was detected in many human
      tissues, and was most abundant in soft connective tissues such as the skin dermis
      and the stroma of various glands. Digital image analysis revealed a linear
      correlation between biotin-HABP and biotin-TSG-6-DeltaHep-Fc staining intensity
      in a subset of normal and malignant human tissues. These results demonstrate that
      TSG-6-DeltaHep-Fc is a sensitive and specific probe for the detection of HA by
      histological methods. 

PMID- 24891597
TI  - Noncontraceptive use of contraceptive agents.
AB  - * On the basis of strong research evidence, there are many noncontraceptive
      advantages to use of hormonal contraceptive agents in adolescent girls. (3)
      (4)(5)(7)(10)(11)(12)(13)(14). * On the basis of research evidence and consensus,
      most of these agents are safe with minor adverse effects.
      (2)(3)(4)(5)(7)(10)(11)(12)(13)(14). * On the basis of research evidence and
      consensus, through application of evidence-based approaches and proper
      counseling, pediatricians can use various contraceptive agents to treat several
      medical conditions and to help alleviate many of the undesired symptoms and
      complications associated with menstrual periods. (2)(3)(4)(5)(7)(10)(11)(12)(13)
      (14). * On the basis of research evidence and consensus, these agents may be used
      in sexually active adolescents to simultaneously help prevent unintended
      adolescent pregnancies. (2)(3)(4)(5)(7)(10)(11)(12)(13)(14).

PMID- 24891598
TI  - Gastrointestinal bleeding.
AB  - * On the basis of strong research evidence, children with severe upper
      gastrointestinal tract bleeding should be treated with intravenous proton pump
      inhibitors. * On the basis of some research evidence and consensus, children with
      severe gastrointestinal bleeding should be evaluated by endoscopy. * On the basis
      of some research evidence and consensus, children in whom endoscopy has not been
      able to confirm a bleeding source should be considered for capsule endoscopy.

PMID- 24891599
TI  - Index of suspicion.

PMID- 24891600
TI  - Shigella.

PMID- 24891601
TI  - Visual diagnosis: Chronic diarrhea and failure to thrive in a 5-year-old girl.
AB  - Chronic GVHD usually develops 100 days after BMT and is a serious and potentially
      life-threatening long-term complication. Chronic GVHD can occur after previous or
      ongoing acute GVHD or in patients without a history of acute GVHD (eg, de novo
      disease) as illustrated by this case. In evaluating a patient presenting with
      chronic diarrhea more than 100 days after BMT, one must consider a serious
      underlying illness such as chronic GVHD because it is a major cause of morbidity
      and mortality of allogeneic stem cell transplantation. As indicated by this case,
      chronic GVHD can cause diarrhea. Complete evaluation of the diarrhea state should
      be part of the initial investigation. In many cases, however, the diagnosis of
      GVHD is not straightforward, and gastrointestinal biopsy and histologic
      confirmation is often necessary to corroborate a clinical impression of chronic
      GVHD.

PMID- 24891602
TI  - Actin and dynamin2 dynamics and interplay during clathrin-mediated endocytosis.
AB  - Clathrin-mediated endocytosis (CME) involves the recruitment of numerous proteins
      to sites on the plasma membrane with prescribed timing to mediate specific stages
      of the process. However, how choreographed recruitment and function of specific
      proteins during CME is achieved remains unclear. Using genome editing to express
      fluorescent fusion proteins at native levels and live-cell imaging with single
      molecule sensitivity, we explored dynamin2 stoichiometry, dynamics, and
      functional interdependency with actin. Our quantitative analyses revealed
      heterogeneity in the timing of the early phase of CME, with transient recruitment
      of 2-4 molecules of dynamin2. In contrast, considerable regularity characterized
      the final 20 s of CME, during which ~26 molecules of dynamin2, sufficient to make
      one ring around the vesicle neck, were typically recruited. Actin assembly
      generally preceded dynamin2 recruitment during the late phases of CME, and
      promoted dynamin recruitment. Collectively, our results demonstrate precise
      temporal and quantitative regulation of the dynamin2 recruitment influenced by
      actin polymerization. 

PMID- 24891604
TI  - Rab18 and a Rab18 GEF complex are required for normal ER structure.
AB  - The ancestral Rab GTPase Rab18 and both subunits of the Rab3GAP complex are
      mutated in the human neurological and developmental disorder Warburg Micro
      syndrome. Here, we demonstrate that the Rab3GAP complex is a specific Rab18
      guanine nucleotide exchange factor (GEF). The Rab3GAP complex localizes to the
      endoplasmic reticulum (ER) and is necessary for ER targeting of Rab18. It is also
      sufficient to promote membrane recruitment of Rab18. Disease-associated point
      mutations of conserved residues in either the Rab3GAP1 (T18P and E24V) or
      Rab3GAP2 (R426C) subunits result in loss of the Rab18 GEF and membrane-targeting
      activities. Supporting the view that Rab18 activity is important for ER
      structure, in the absence of either Rab3GAP subunit or Rab18 function, ER tubular
      networks marked by reticulon 4 were disrupted, and ER sheets defined by CLIMP-63
      spread out into the cell periphery. Micro syndrome is therefore a disease
      characterized by direct loss of Rab18 function or loss of Rab18 activation at the
      ER by its GEF Rab3GAP. 

PMID- 24891603
TI  - Talin regulates moesin-NHE-1 recruitment to invadopodia and promotes mammary
      tumor metastasis.
AB  - Invadopodia are actin-rich protrusions that degrade the extracellular matrix and
      are required for stromal invasion, intravasation, and metastasis. The role of the
      focal adhesion protein talin in regulating these structures is not known. Here,
      we demonstrate that talin is required for invadopodial matrix degradation and
      three-dimensional extracellular matrix invasion in metastatic breast cancer
      cells. The sodium/hydrogen exchanger 1 (NHE-1) is linked to the cytoskeleton by
      ezrin/radixin/moesin family proteins and is known to regulate invadopodium
      mediated matrix degradation. We show that the talin C terminus binds directly to
      the moesin band 4.1 ERM (FERM) domain to recruit a moesin-NHE-1 complex to
      invadopodia. Silencing talin resulted in a decrease in cytosolic pH at
      invadopodia and blocked cofilin-dependent actin polymerization, leading to
      impaired invadopodium stability and matrix degradation. Furthermore, talin is
      required for mammary tumor cell motility, intravasation, and spontaneous lung
      metastasis in vivo. Thus, our findings provide a novel understanding of how
      intracellular pH is regulated and a molecular mechanism by which talin enhances
      tumor cell invasion and metastasis.

PMID- 24891607
TI  - Pulmonary pathologic manifestations of anti-glycyl-tRNA synthetase (anti-EJ)
      related inflammatory myopathy.
AB  - AIMS: Antisynthetase syndromes are a subset of the idiopathic inflammatory
      myopathies characterised by the presence of autoantibodies to aminoacyl transfer
      RNA synthetases (ARS) and monotypic clinical features including Raynaud
      phenomenon, fever, non-erosive inflammatory arthritis and hyperkeratotic skin
      changes ('mechanic's hands'). Interstitial lung disease (ILD) is particularly
      common in ARS syndromes, affecting up to 90% of patients. METHODS: Four patients
      with ARS syndrome who possessed anti-glycyl-tRNA synthetase (anti-EJ)
      autoantibodies were retrieved from the University of Pittsburgh database. We
      report their clinical, radiographic and histopathologic findings. RESULTS:
      Patients presented with dyspnoea accompanied by Raynaud phenomenon and
      'mechanic's hands'. Lung disease was the first manifestation in all four patients
      (100%) who were all amyopathic. High-resolution CT of the chest showed patchy
      opacities and consolidations in two patients (50%) whose surgical lung biopsies
      revealed organising diffuse alveolar damage (DAD), and lower lung zone
      predominant reticular infiltrates and traction bronchiectasis without honeycomb
      change in two patients (50%) whose surgical lung biopsies revealed usual
      interstitial pneumonia (UIP). Mild lymphoplasmacytic inflammation and few
      scattered lymphoid aggregates were present, but we found no pathognomonic
      histopathologic features of anti-EJ ARS syndrome. Serologic testing revealed no
      other autoantibodies. All patients responded to immunosuppressive therapy.
      CONCLUSIONS: Identifying ARS-associated autoantibodies in ILD patients with or
      without myopathy is desirable because patients may respond well to
      immunosuppressive therapy, and their prognosis is better than that of patients
      with idiopathic forms of DAD or UIP.

PMID- 24891605
TI  - Identification of unique SUN-interacting nuclear envelope proteins with diverse
      functions in plants.
AB  - Although a plethora of nuclear envelope (NE) transmembrane proteins (NETs) have
      been identified in opisthokonts, plant NETs are largely unknown. The only known
      NET homologues in plants are Sad1/UNC-84 (SUN) proteins, which bind Klarsicht/ANC
      1/Syne-1 homology (KASH) proteins. Therefore, de novo identification of plant
      NETs is necessary. Based on similarities between opisthokont KASH proteins and
      the only known plant KASH proteins, WPP domain-interacting proteins, we used a
      computational method to identify the KASH subset of plant NETs. Ten potential
      plant KASH protein families were identified, and five candidates from four of
      these families were verified for their NE localization, depending on SUN domain
      interaction. Of those, Arabidopsis thaliana SINE1 is involved in actin-dependent
      nuclear positioning in guard cells, whereas its paralogue SINE2 contributes to
      innate immunity against an oomycete pathogen. This study dramatically expands our
      knowledge of plant KASH proteins and suggests that plants and opisthokonts have
      recruited different KASH proteins to perform NE regulatory functions.

PMID- 24891606
TI  - Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of
      excess precrossover sites.
AB  - Meiotic crossovers (COs) are crucial for ensuring accurate homologous chromosome
      segregation during meiosis I. Because the double-strand breaks (DSBs) that
      initiate meiotic recombination greatly outnumber eventual COs, this process
      requires exquisite regulation to narrow down the pool of DSB intermediates that
      may form COs. In this paper, we identify a cyclin-related protein, CNTD1, as a
      critical mediator of this process. Disruption of Cntd1 results in failure to
      localize CO-specific factors MutLgamma and HEI10 at designated CO sites and also
      leads to prolonged high levels of pre-CO intermediates marked by MutSgamma and
      RNF212. These data show that maturation of COs is intimately coupled to
      deselection of excess pre-CO sites to yield a limited number of COs and that
      CNTD1 coordinates these processes by regulating the association between the RING
      finger proteins HEI10 and RNF212 and components of the CO machinery. 

PMID- 24891608
TI  - Ike's monument: every gun is a theft.

PMID- 24891609
TI  - FASEB Science Research Conference on Biology and Chemistry of Vision.

PMID- 24891610
TI  - Cotyledon-Generated Auxin Is Required for Shade-Induced Hypocotyl Growth in
      Brassica rapa.
AB  - Plant architecture is optimized for the local light environment. In response to
      foliar shade or neighbor proximity (low red to far-red light), some plant species
      exhibit shade-avoiding phenotypes, including increased stem and hypocotyl growth,
      which increases the likelihood of outgrowing competitor plants. If shade
      persists, early flowering and the reallocation of growth resources to stem
      elongation ultimately affect the yield of harvestable tissues in crop species.
      Previous studies have shown that hypocotyl growth in low red to far-red shade is
      largely dependent on the photoreceptor phytochrome B and the phytohormone auxin.
      However, where shade is perceived in the plant and how auxin regulates growth
      spatially are less well understood. Using the oilseed and vegetable crop species
      Brassica rapa, we show that the perception of low red to far-red shade by the
      cotyledons triggers hypocotyl cell elongation and auxin target gene expression.
      Furthermore, we find that following shade perception, elevated auxin levels occur
      in a basipetal gradient away from the cotyledons and that this is coincident with
      a gradient of auxin target gene induction. These results show that cotyledon
      generated auxin regulates hypocotyl elongation. In addition, we find in mature B.
      rapa plants that simulated shade does not affect seed oil composition but may
      affect seed yield. This suggests that in field settings where mutual shading
      between plants may occur, a balance between plant density and seed yield per
      plant needs to be achieved for maximum oil yield, while oil composition might
      remain constant.

PMID- 24891611
TI  - Root cortical aerenchyma enhances nitrogen acquisition from low-nitrogen soils in
      maize.
AB  - Suboptimal nitrogen (N) availability is a primary constraint for crop production
      in developing nations, while in rich nations, intensive N fertilization carries
      substantial environmental and economic costs. Therefore, understanding root
      phenes that enhance N acquisition is of considerable importance. Structural
      functional modeling predicts that root cortical aerenchyma (RCA) could improve N
      acquisition in maize (Zea mays). We evaluated the utility of RCA for N
      acquisition by physiological comparison of maize recombinant inbred lines
      contrasting in RCA grown under suboptimal and adequate N availability in
      greenhouse mesocosms and in the field in the United States and South Africa. N
      stress increased RCA formation by 200% in mesocosms and by 90% to 100% in the
      field. RCA formation substantially reduced root respiration and root N content.
      Under low-N conditions, RCA formation increased rooting depth by 15% to 31%,
      increased leaf N content by 28% to 81%, increased leaf chlorophyll content by
      22%, increased leaf CO2 assimilation by 22%, increased vegetative biomass by 31%
      to 66%, and increased grain yield by 58%. Our results are consistent with the
      hypothesis that RCA improves plant growth under N-limiting conditions by
      decreasing root metabolic costs, thereby enhancing soil exploration and N
      acquisition in deep soil strata. Although potential fitness tradeoffs of RCA
      formation are poorly understood, increased RCA formation appears be a promising
      breeding target for enhancing crop N acquisition. 

PMID- 24891612
TI  - Auxin Input Pathway Disruptions Are Mitigated by Changes in Auxin Biosynthetic
      Gene Expression in Arabidopsis.
AB  - Auxin is a phytohormone involved in cell elongation and division. Levels of
      indole-3-acetic acid (IAA), the primary auxin, are tightly regulated through
      biosynthesis, degradation, sequestration, and transport. IAA is sequestered in
      reversible processes by adding amino acids, polyol or simple alcohols, or sugars,
      forming IAA conjugates, or through a two-carbon elongation forming indole-3
      butyric acid. These sequestered forms of IAA alter hormone activity. To gain a
      better understanding of how auxin homeostasis is maintained, we have generated
      Arabidopsis (Arabidopsis thaliana) mutants that combine disruptions in the
      pathways, converting IAA conjugates and indole-3-butyric acid to free IAA. These
      mutants show phenotypes indicative of low auxin levels, including delayed
      germination, abnormal vein patterning, and decreased apical dominance. Root
      phenotypes include changes in root length, root branching, and root hair growth.
      IAA levels are reduced in the cotyledon tissue but not meristems or hypocotyls.
      In the combination mutants, auxin biosynthetic gene expression is increased,
      particularly in the YUCCA/Tryptophan Aminotransferase of Arabidopsis1 pathway,
      providing a feedback mechanism that allows the plant to compensate for changes in
      IAA input pathways and maintain cellular homeostasis.

PMID- 24891613
TI  - Genome-wide identification of long intergenic noncoding RNA genes and their
      potential association with domestication in pigs.
AB  - Thousands of long intergenic noncoding RNAs (lincRNAs) have been identified in
      the human and mouse genomes, some of which play important roles in fundamental
      biological processes. The pig is an important domesticated animal, however, pig
      lincRNAs remain poorly characterized and it is unknown if they were involved in
      the domestication of the pig. Here, we used available RNA-seq resources derived
      from 93 samples and expressed sequence tag data sets, and identified 6,621
      lincRNA transcripts from 4,515 gene loci. Among the identified lincRNAs, some
      lincRNA genes exhibit synteny and sequence conservation, including linc-sscg2561,
      whose gene neighbor Dnmt3a is associated with emotional behaviors. Both linc
      sscg2561 and Dnmt3a show differential expression in the frontal cortex between
      domesticated pigs and wild boars, suggesting a possible role in pig
      domestication. This study provides the first comprehensive genome-wide analysis
      of pig lincRNAs. 

PMID- 24891614
TI  - Role of Wnt5a-Ror2 signaling in morphogenesis of the metanephric mesenchyme
      during ureteric budding.
AB  - Development of the metanephric kidney begins with the induction of a single
      ureteric bud (UB) on the caudal Wolffian duct (WD) in response to GDNF (glial
      cell line-derived neurotrophic factor) produced by the adjacent metanephric
      mesenchyme (MM). Mutual interaction between the UB and MM maintains expression of
      GDNF in the MM, thereby supporting further outgrowth and branching morphogenesis
      of the UB, while the MM also grows and aggregates around the branched tips of the
      UB. Ror2, a member of the Ror family of receptor tyrosine kinases, has been shown
      to act as a receptor for Wnt5a to mediate noncanonical Wnt signaling. We show
      that Ror2 is predominantly expressed in the MM during UB induction and that Ror2-
      and Wnt5a-deficient mice exhibit duplicated ureters and kidneys due to ectopic UB
      induction. During initial UB formation, these mutant embryos show dysregulated
      positioning of the MM, resulting in spatiotemporally aberrant interaction between
      the MM and WD, which provides the WD with inappropriate GDNF signaling.
      Furthermore, the numbers of proliferating cells in the mutant MM are markedly
      reduced compared to the wild-type MM. These results indicate an important role of
      Wnt5a-Ror2 signaling in morphogenesis of the MM to ensure proper epithelial
      tubular formation of the UB required for kidney development. 

PMID- 24891616
TI  - RORalpha binds to E2F1 to inhibit cell proliferation and regulate mammary gland
      branching morphogenesis.
AB  - Retinoic acid receptor-related orphan nuclear receptor alpha (RORalpha) is a
      potent tumor suppressor that reduces cell proliferation and inhibits tumor
      growth. However, the molecular mechanism by which it inhibits cell proliferation
      remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which
      RORalpha binds to E2F1 to inhibit cell cycle progression. We showed that RORalpha
      bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1
      regulated transcription in epithelial cells. Binding of RORalpha inhibited E2F1
      acetylation and its DNA-binding activity by recruiting histone deacetylase 1
      (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC
      activity at least partially rescued transcription factor activity of E2F1 that
      was repressed by RORalpha. Importantly, RORalpha levels were increased in mammary
      ducts compared to terminal end buds and inversely correlated with expression of
      E2F1 target genes and cell proliferation. Silencing RORalpha in mammary
      epithelial cells significantly enhanced cell proliferation in the ductal
      epithelial cells and promoted side branching of the mammary ducts. These results
      reveal a novel link between RORalpha and E2F1 in regulating cell cycle
      progression and mammary tissue morphogenesis. 

PMID- 24891617
TI  - Direct transcriptional repression of Zfp423 by Zfp521 mediates a bone morphogenic
      protein-dependent osteoblast versus adipocyte lineage commitment switch.
AB  - Osteoblasts and adipocytes arise from a common mesenchymal precursor cell. The
      cell fate decision of a mesenchymal precursor cell is under the influence of
      molecular cues and signaling pathways that lead to the activation or repression
      of lineage-specific transcription factors. The molecular mechanisms determining
      osteoblast versus adipocyte lineage specificity in response to bone morphogenic
      protein (BMP) remain unclear. In this study, we describe the mechanism through
      which Zfp521 (ZNF521), a regulator of lineage progression in multiple immature
      cell populations, regulates lineage specification of mesenchymal progenitor cells
      during BMP-induced differentiation events. In vivo deletion or in vitro knockdown
      of Zfp521 in mesenchymal precursors resulted in increased expression of the
      adipocyte determinant factor Zfp423 (ZNF423). This was concurrent with the loss
      of histone H3K9 methylation and an increase in histone H3K9 acetylation at the
      Zfp423 promoter, which together are indicative of decreased gene repression.
      Indeed, we found that Zfp521 occupies and represses the promoter and intronic
      enhancer regions of Zfp423. Accordingly, conditional deletion of Zfp521 inhibited
      heterotopic bone formation in response to local injection of BMP2. In contrast,
      marrow adiposity within BMP2-induced bone was markedly enhanced in Zfp521
      deficient mice, suggesting that precursor cells lacking Zfp521 differentiate
      preferentially into adipocytes instead of osteoblasts in response to BMP2.
      Consistent with a cell-autonomous role of Zfp521 in mesenchymal precursors,
      knockdown of Zfp521 in stromal cells prevented BMP2-induced osteoblast marker
      expression and simultaneously enhanced lipid accumulation and expression of
      adipocyte-related genes. Taken together, the data suggest that Zfp521 is a cell
      fate switch critical for BMP-induced osteoblast commitment and identify Zfp521 as
      the intrinsic repressor of Zfp423 and hence of adipocyte commitment during BMP
      induced mesenchymal precursor differentiation. 

PMID- 24891615
TI  - Chromatinized protein kinase C-theta directly regulates inducible genes in
      epithelial to mesenchymal transition and breast cancer stem cells.
AB  - Epithelial to mesenchymal transition (EMT) is activated during cancer invasion
      and metastasis, enriches for cancer stem cells (CSCs), and contributes to
      therapeutic resistance and disease recurrence. Signal transduction kinases play a
      pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the
      first time that protein kinase C-theta (PKC-theta) promotes EMT by acting as a
      critical chromatin-anchored switch for inducible genes via transforming growth
      factor beta (TGF-beta) and the key inflammatory regulatory protein NF-kappaB.
      Chromatinized PKC-theta exists as an active transcription complex and is required
      to establish a permissive chromatin state at signature EMT genes. Genome-wide
      analysis identifies a unique cohort of inducible PKC-theta-sensitive genes that
      are directly tethered to PKC-theta in the mesenchymal state. Collectively, we
      show that cross talk between signaling kinases and chromatin is critical for
      eliciting inducible transcriptional programs that drive mesenchymal
      differentiation and CSC formation, providing novel mechanisms to target using
      epigenetic therapy in breast cancer. 

PMID- 24891618
TI  - Overexpression of epigen during embryonic development induces reversible,
      epidermal growth factor receptor-dependent sebaceous gland hyperplasia.
AB  - The epidermal growth factor receptor (EGFR) system is a key regulator of
      epithelial development and homeostasis. Its functions in the sebaceous gland
      (SG), however, remain poorly characterized. In this study, using a transgenic
      mouse line with tissue-specific and inducible expression of the EGFR ligand
      epigen, we showed that increased activation of the EGFR in skin keratinocytes
      results in enlarged SGs and increased sebum production. The phenotype can be
      reverted by interrupting transgene expression and is EGFR dependent, as gland
      size and sebum levels return to normal values after crossing to the EGFR-impaired
      mouse line Wa5. Intriguingly, however, the SG enlargement appears only if EGFR
      activation occurs before birth. Importantly, the enlarged sebaceous glands are
      associated with an increased expression of the transcription factor MYC and of
      the transmembrane proteins LRIG1, an established negative-feedback regulator of
      the EGFR/ERBB tyrosine kinase receptors and a stem cell marker. Our findings
      identify EGFR signaling as a major pathway determining SG activity and suggest a
      functional relationship between the EGFR/ERBB system and MYC/LRIG1 in the
      commitment of stem cells toward specific progenitor cell types, with implications
      for our understanding of their role in tissue development, homeostasis, and
      disease. 

PMID- 24891619
TI  - RNA-binding protein AUF1 promotes myogenesis by regulating MEF2C expression
      levels.
AB  - The mammalian RNA-binding protein AUF1 (AU-binding factor 1, also known as
      heterogeneous nuclear ribonucleoprotein D [hnRNP D]) binds to numerous mRNAs and
      influences their posttranscriptional fate. Given that many AUF1 target mRNAs
      encode muscle-specific factors, we investigated the function of AUF1 in skeletal
      muscle differentiation. In mouse C2C12 myocytes, where AUF1 levels rise at the
      onset of myogenesis and remain elevated throughout myocyte differentiation into
      myotubes, RNP immunoprecipitation (RIP) analysis indicated that AUF1 binds
      prominently to Mef2c (myocyte enhancer factor 2c) mRNA, which encodes the key
      myogenic transcription factor MEF2C. By performing mRNA half-life measurements
      and polysome distribution analysis, we found that AUF1 associated with the 3'
      untranslated region (UTR) of Mef2c mRNA and promoted MEF2C translation without
      affecting Mef2c mRNA stability. In addition, AUF1 promoted Mef2c gene
      transcription via a lesser-known role of AUF1 in transcriptional regulation.
      Importantly, lowering AUF1 delayed myogenesis, while ectopically restoring MEF2C
      expression levels partially rescued the impairment of myogenesis seen after
      reducing AUF1 levels. We propose that MEF2C is a key effector of the myogenesis
      program promoted by AUF1. 

PMID- 24891621
TI  - The foreclosure crisis and cardiovascular disease.

PMID- 24891620
TI  - Hypoxia-inducible factor/MAZ-dependent induction of caveolin-1 regulates colon
      permeability through suppression of occludin, leading to hypoxia-induced
      inflammation.
AB  - Caveolae are specialized microdomains on membranes that are critical for signal
      transduction, cholesterol transport, and endocytosis. Caveolin-1 (CAV1) is a
      multifunctional protein and a major component of caveolae. Cav1 is directly
      activated by hypoxia-inducible factor (HIF). HIFs are heterodimers of an oxygen
      sensitive alpha subunit, HIF1alpha or HIF2alpha, and a constitutively expressed
      beta subunit, aryl hydrocarbon receptor nuclear translocator (ARNT). Whole-genome
      expression analysis demonstrated that Cav1 is highly induced in mouse models of
      constitutively activated HIF signaling in the intestine. Interestingly, Cav1 was
      increased only in the colon and not in the small intestine. Currently, the
      mechanism and role of HIF induction of CAV1 in the colon are unclear. In mouse
      models, mice that overexpressed HIF1alpha or HIF2alpha specifically in intestinal
      epithelial cells demonstrated an increase in Cav1 gene expression in the colon
      but not in the duodenum, jejunum, or ileum. HIF2alpha activated the Cav1 promoter
      in a HIF response element-independent manner. myc-associated zinc finger (MAZ)
      protein was essential for HIF2alpha activation of the Cav1 promoter. Hypoxic
      induction of CAV1 in the colon was essential for intestinal barrier integrity by
      regulating occludin expression. This may provide an additional mechanism by which
      chronic hypoxia can activate intestinal inflammation. 

PMID- 24891622
TI  - Effects of proximate foreclosed properties on individuals' systolic blood
      pressure in Massachusetts, 1987 to 2008.
AB  - BACKGROUND: No studies have examined the effects of local foreclosure activity on
      neighbors' blood pressure, despite the fact that spillover effects of nearby
      foreclosures include many known risk factors for increased blood pressure. We
      assessed the extent to which living near foreclosed properties is associated with
      subsequent systolic blood pressure (SBP) measurements. METHODS AND RESULTS: We
      used 6590 geocoded observations collected from 1740 participants in the
      Framingham Offspring Cohort across 5 waves (1987-2008) of the Framingham Heart
      Study to create a longitudinal record of exposure to nearby foreclosure activity.
      We distinguished between real estate-owned foreclosures, which typically sit
      vacant, and foreclosures purchased by third-party buyers, which are generally put
      into productive use. Counts of lender-owned foreclosed properties within 100 m of
      participants' homes were used to predict measured SBP and odds of being
      hypertensive. We assessed whether self-reported alcoholic drinks per week and
      measured body mass index helped to explain the relationship between foreclosure
      activity and SBP. Each additional real estate-owned foreclosure located within
      100 m of a participant's home was associated with an increase in SBP of 1.71 mm
      Hg (P=0.03; 95% confidence interval, 0.18-3.24) after adjustment for individual-
      and area-level confounders but not with odds of hypertension. The presence of
      foreclosures purchased by third-party buyers was not associated with SBP or with
      hypertension. Body mass index and alcohol consumption attenuated the effect of
      living near real estate-owned foreclosures on SBP in fully adjusted models.
      CONCLUSIONS: Real estate-owned foreclosed properties may put nearby neighbors at
      risk for increased SBP, with higher alcohol consumption and body mass index
      partially mediating this relationship.

PMID- 24891623
TI  - Glucagon-like peptide-1 receptor agonists for diabetes mellitus: a role in
      cardiovascular disease.

PMID- 24891624
TI  - Transplantation in the highly sensitized pediatric patient.
AB  - Sensitization against HLA antigens is a growing problem in the field of pediatric
      cardiac transplantation. Although surgical outcomes for congenital heart disease
      have improved over the decades, these successes have added to the growing list of
      sensitized patients who eventually may require transplantation.Cardiac
      transplantation survival has improved, but morbidity and mortality secondary to
      HLA antibodies hinder outcome. Aside from acute hemodynamic compromise, there is
      compelling evidence linking sensitization and AMR with the development of CAV, a
      major limiting factor affecting long-term graft survival. Clinical advances have
      improved our understanding of the roles of antibody type, CFAs and non-CFAs, and
      DSAs and non-DSAs. Therapeutic strategies target both the T- and B-cell lines.
      Combinations that include plasmapheresis, IVIG, cyclophosphamide, and rituximab
      have been used in clinical studies with variable success.Two newer agents show
      promise, targeting both ends of the antibody-mediated spectrum: Bortezomib
      depletes plasma cell populations, and eculizumab blocks the terminal effects of
      antibody action, thus preventing myocardial cell dysfunction and death. Despite
      numerous diagnostic and therapeutic advances, many questions remain about the
      best approaches.The role of HLA antibodies remains the central target of
      investigation.

PMID- 24891626
TI  - ECG Response: June 3, 2014.

PMID- 24891625
TI  - Subclavian steal syndrome.
AB  - "Subclavian steal" refers to a syndrome of symptoms relating to arterial
      insufficiency in a branch of the subclavian artery stemming from flow
      reversal,attributable to occlusive disease in the subclavian artery proximal to
      that branch that is usually atheroscleroticin cause. Most patients are
      asymptomatic,but patients with IMA bypass grafts may manifest angina elicited by
      exercise of the upper extremity ipsilateral to the graft and stenosis (so
      called"coronary-subclavian steal").Subclavian steal may also manifest as
      vertebrobasilar insufficiency or,most commonly, arm claudication.Subclavian steal
      should be considered among patients exhibiting suggestive symptoms. A meticulous
      examination of segmental pulses and pressures,as well as judicious use of duplex
      ultrasonography, magnetic resonance angiography, computed tomography angiography,
      or conventional angiography can confirm the presence of subclavian stenosis.
      Symptomatic patients benefit from either percutaneousor surgical
      revascularization,depending on both anatomic and patient factors. Subclavian
      stenosis,regardless of symptoms, is a marker of atherosclerotic disease and
      increased risk for cardiovascular and cerebrovascular events.

PMID- 24891627
TI  - Regression of cardiac amyloidosis after stem cell transplantation assessed by
      cardiovascular magnetic resonance imaging.

PMID- 24891628
TI  - Detection of internal thoracic artery dissection at coronary anastomosis using
      intraoperative 15-MHz high-frequency epicardial ultrasound.

PMID- 24891629
TI  - Letter by Tsikas and Cooper regarding article, "dysregulation of hydrogen sulfide
      (H2S) producing enzyme cystathionine gamma-lyase (CSE) contributes to maternal
      hypertension and placental abnormalities in preeclampsia".

PMID- 24891631
TI  - Ethical question on food animal practitioner treating mange--a comment.

PMID- 24891630
TI  - Response to letter regarding article, "dysregulation of hydrogen sulfide (H2S)
      producing enzyme cystathionine gamma-lyase (CSE) contributes to maternal
      hypertension and placental abnormalities in preeclampsia".

PMID- 24891633
TI  - Corporate veterinary medicine.

PMID- 24891634
TI  - Veterinary medical ethics. An ethicist's commentary on animal health and welfare.
AB  - Veterinarians working with racehorses face unique challenges. No other type of
      practice expects veterinarians to "correct" such minute deficiencies in
      performance. Since the actual performance potential of many horses cannot be
      known, treatments may be targeted at "perceived" deficiencies in performance.
      Nevertheless, seconds or fractions of a second determine profit and loss and thus
      the animal's value for the trainer and owner. One or two seconds may ultimately
      determine whether a horse continues racing or is sold for slaughter. Is a
      veterinarian who works to maintain or improve racehorse performance in keeping
      with the veterinarian's oath to "promote animal health and welfare?"

PMID- 24891635
TI  - Congenital urethral stenosis in a male miniature piglet.
AB  - A 2-month-old male miniature pig showed progressive abdominal pain, pollakiuria,
      and stranguria that progressed to complete urinary obstruction. Postmortem
      examination revealed idiopathic urethral stenosis at the level of the recess, of
      probable congenital origin. Urinary tract malformations should be included in the
      differential diagnosis of miniature piglets with urinary disorders. 

PMID- 24891636
TI  - Cecal vascular hamartoma causing recurrent colic in an Arabian mare.
AB  - A 5-year-old mare was treated for recurrent colic and weight loss by surgical
      removal of an intraluminal cecal mass. Microscopic examination revealed vascular
      hamartoma. A 6-month follow-up showed an improvement in the general condition of
      the mare. Vascular hamartoma should be one of the differential diagnoses for
      weight loss and colic. 

PMID- 24891637
TI  - Hepatic alveolar hydatid disease (Echinococcus multilocularis) in a boxer dog
      from southern Ontario.
AB  - A 2-year-old boxer dog from southern Ontario was evaluated because of acute onset
      lethargy. Exploratory laparotomy revealed a hemorrhagic, destructive, liver mass.
      Histology, immunohistochemistry, and polymerase chain reaction confirmed
      Echinococcus multilocularis as the cause of the hepatic mass. This constitutes
      the first description of endemic E. multilocularis in Ontario. 

PMID- 24891638
TI  - Sinusitis associated with nasogastric intubation in 3 horses.
AB  - Sinusitis has not been reported as a complication of long-term nasogastric
      intubation in horses. We describe 3 horses that developed nosocomial sinusitis
      following abdominal surgery with associated perioperative nasogastric intubation.
      Sinusitis was suspected by the presence of malodorous discharge and confirmed by
      percussion, upper airway endoscopy, radiographs (n = 3), and bacterial culture (n
      = 1). 

PMID- 24891639
TI  - Ruminal acidosis in a 21-month-old Holstein heifer.
AB  - Rumen and blood biochemical profiles were monitored in 8 Holstein heifers exposed
      to a carbohydrate feeding challenge. One of the heifers had clinical signs
      consistent with acute ruminal acidosis on the day of, and subsequent to, the
      challenge. Within 24 h of challenge, 6 of 7 rumen volatile fatty acids measured
      were not detectable in this heifer and her rumen total lactate concentration was
      > 70 mM. 

PMID- 24891640
TI  - Management of dogs and cats with endotracheal tube tracheal foreign bodies.
AB  - Two cats and 3 dogs were treated for an endotracheal tube tracheal foreign body
      (ETFB) during recovery from general anesthesia. Bronchoscopy was used to remove
      the ETFB. Animals were clinically normal at discharge. While rare, ETFB can occur
      upon recovery from anesthesia. Bronchoscopy is an effective way to remove ETFB. 

PMID- 24891641
TI  - Endoscopy-guided ectopic egg removal from the urinary bladder in a leopard
      tortoise (Stigmochelys pardalis).
AB  - Egg retention in the urinary bladder of a leopard tortoise was diagnosed by
      radiography and confirmed by cystoscopy. The egg was removed with a modified
      polypectomy snare, aided by a flexible endoscope and insufflation. No
      complications occurred during the procedures and the tortoise made a complete
      recovery. 

PMID- 24891642
TI  - Copper-associated hepatitis in a Pembroke Welsh corgi.
AB  - A 6-year-old spayed female Pembroke Welsh corgi dog was diagnosed with copper
      associated hepatitis; an uncommon disease to which a variety of breeds are
      predisposed. This case report describes copper-associated hepatitis in a breed in
      which the disease has not previously been reported. 

PMID- 24891643
TI  - Mandibular condylectomy in a cow with a chronic luxation of the temporomandibular
      joint.
AB  - A cow, presented after being struck by a motor vehicle, continued to have
      difficulty eating after mandibular fracture repair. Imaging showed a
      temporomandibular luxation and a mandibular condylectomy was performed.
      Mastication improved greatly but the cow was euthanized due to infection. This is
      the first report of mandibular condylectomy in cattle. 

PMID- 24891644
TI  - Comparison of commercial progesterone assays for evaluation of luteal status in
      dairy cows.
AB  - Serum progesterone (P4) concentration was measured using 2 methods, and ovaries
      were examined by ultrasonography (US) to determine the presence of a corpus
      luteum (CL) in 101 lactating dairy cows. The concordance correlation coefficient
      between the 2 methods (Ovucheck and Immulite P4 assays) was high (rhoc = 0.94);
      agreement between the assays on presence of a CL based on P4 > 1 ng/mL was
      excellent (Kappa = 0.88) and of each assay with US was good (Kappa = 0.63 for
      each). 

PMID- 24891646
TI  - Livestock and poultry fitness for transport--the veterinarian's role.

PMID- 24891645
TI  - Uveodermatologic syndrome concurrent with keratoconjunctivitis sicca in a
      miniature poodle dog.
AB  - A 5-year-old, intact female miniature poodle dog was presented with chronic
      ophthalmic problems, facial poliosis, nasal depigmentation and multiple areas of
      alopecia over the trunk. Bilateral uveitis preceded dermatologic signs by 5
      months and gradually worsened. The dog was diagnosed as having uveodermatologic
      syndrome (UDS) concurrent with keratoconjunctivitis sicca (KCS). Treatment with
      immunosuppressive drugs resolved the dermatologic lesions, but uveitis continued
      to progress. 

PMID- 24891647
TI  - Contagious communication.

PMID- 24891648
TI  - Hand eczema.
AB  - Hand eczema is often a chronic, multifactorial disease. It is usually related to
      occupational or routine household activities. Exact etiology of the disease is
      difficult to determine. It may become severe enough and disabling to many of
      patients in course of time. An estimated 2-10% of population is likely to develop
      hand eczema at some point of time during life. It appears to be the most common
      occupational skin disease, comprising 9-35% of all occupational diseases and up
      to 80% or more of all occupational contact dermatitis. So, it becomes important
      to find the exact etiology and classification of the disease and to use the
      appropriate preventive and treatment measures. Despite its importance in the
      dermatological practice, very few Indian studies have been done till date to
      investigate the epidemiological trends, etiology, and treatment options for hand
      eczema. In this review, we tried to find the etiology, epidemiology, and
      available treatment modalities for chronic hand eczema patients. 

PMID- 24891649
TI  - Caveolin-1 expression in different types of psoriatic lesions: analysis of 66
      cases.
AB  - BACKGROUND: Caveolin-1 is a key structural and functional protein. Caveolin-1 is
      known to modulate multiple signal-transducing pathways involved in cell
      differentiation and proliferation. Psoriasis is viewed as a multifactorial
      pathology characterized by keratinocyte hyperproliferation and abnormal cell
      maturation. OBJECTIVES: To examine the expression of caveolin-1 in skin biopsies
      from normal subjects, patients, and subjects with the three respective isoforms
      of psoriasis (psoriasis vulgaris, localized pustular psoriasis, and erythrodermic
      psoriasis). The expression level of caveolin-1 was compared among psoriasis
      vulgaris, localized pustular psoriasis, erythrodermic psoriasis, and normal
      subjects. MATERIALS AND METHODS: Using immunohistochemical methods, caveolin-1
      protein expression was assayed in four groups. An analysis was conducted on skin
      samples obtained from 22 normal subjects and 28 patients with psoriasis vulgaris,
      22 patients with localized pustular psoriasis, and 16 patients with erythrodermic
      psoriasis. The statistical analysis of the scoring criteria reflecting the level
      of Caveolin-1 immunostaining between different groups was determined using the
      Mann-Whitney U-test. RESULTS: In the normal skin, intense and consistent caveolin
      1 staining was present in 22 cases. The Caveolin-1 protein was significantly
      reduced and showed very weak or absent staining within the tissues of psoriasis
      vulgaris, localized pustular psoriasis, and erythrodermic psoriasis (respective P
      < 0.001). Caveolin-1 protein expression in psoriasis vulgaris was higher than
      that in localized pustular psoriasis and erythrodermic psoriasis (respective P <
      0.05). Caveolin-1 protein expression was no different in localized pustular
      psoriasis and erythrodermic psoriasis (P > 0.05). CONCLUSION: The finding of this
      study was consistent with a downregulation of Caveolin-1, which might serve as an
      etiological factor in the development of psoriasis vulgaris, localized pustular
      psoriasis, and erythrodermic psoriasis. Further mechanistic investigations are
      required to prove that Caveolin-1 protein has the potential and may be a novel
      target for therapy of psoriasis vulgaris, localized pustular psoriasis, and
      erythrodermic psoriasis.

PMID- 24891650
TI  - Apoptosis and clinical severity in patients with psoriasis and HCV infection.
AB  - BACKGROUND: It has been proposed that hepatitis C virus (HCV) antigens are
      involved in the pathogenesis of psoriasis and may contribute to severity of the
      disease. Increased expression of the apoptosis-regulating proteins p53 and tTG
      and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic
      patients have been reported. AIM: This study aims to identify the serum levels of
      apoptosis-regulating proteins in patients with psoriasis and without HCV
      infection and to study the relation between clinical severity of psoriasis and
      the presence of HCV infection. MATERIALS AND METHODS: Disease severity was
      assessed by psoriasis area severity index score (PASI) of 90 patients with
      psoriasis grouped as mild (n = 30), moderate (n = 30) and severe (n = 30); 20
      healthy individuals were used as controls. All groups were subjected for complete
      history taking, clinical examination, and tests for liver function and HCV
      infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2
      were estimated by enzyme linked immune sorbent assay (ELISA). RESULTS: There was
      a statistically significant (P < 0.001) correlation between clinical severity of
      psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly
      (P < 0.001) raised serum p53 and tTG, and reduced bcl-2 were observed among HCV
      positive patients as compared to HCV-negative patients and control patients.
      CONCLUSION: These results conclude that clinical severity of psoriasis is
      affected by the presence of HCV antibodies and overexpression of apoptotic
      related proteins. In addition, altered serum levels of apoptosis-regulating
      proteins could be useful prognostic markers and therapeutic targets of psoriatic
      disease.

PMID- 24891652
TI  - Severity of Psoriasis Among Adult Males is Associated with Smoking, Not with
      Alcohol Use.
AB  - CONTEXT: Lifestyle factors such as tobacco smoking and alcohol use can affect the
      presentation and course of psoriasis. There is a paucity of data on this subject
      from India. AIMS: To find out whether increased severity of psoriasis in adult
      Indian males is associated with tobacco smoking and alcohol use. SETTINGS AND
      DESIGN: Cross-sectional study in the Department of Dermatology of a Tertiary Care
      Teaching Hospital. SUBJECTS AND METHODS: Male patients above 18 years of age
      attending a psoriasis clinic between March 2007 and May 2009 were studied.
      Severity of psoriasis (measured using Psoriasis Area and Severity Index - PASI)
      among smokers and non-smokers was compared. We also studied the correlation
      between severity of psoriasis and nicotine dependence (measured using Fagerstrom
      Test for Nicotine Dependence) and alcohol use disorders (measured using Alcohol
      Use Disorders Identification Test-AUDIT). STATISTICAL ANALYSIS: Z-test, Odd's
      ratio, Chi-square test, Spearman's correlation coefficient. RESULTS: Of a total
      of 338 patients, 148 were smokers and 173 used to consume alcohol. Mean PASI
      score of smokers was more than that of non-smokers (Z-test, z = -2.617, P =
      0.009). Those with severe psoriasis were more likely to be smokers (chi(2) =
      5.47, P = 0.02, OR = 1.8, Confidence Interval 1.09-2.962). There was a
      significant correlation between PASI scores and Fagerstrom score (Spearman's
      correlation coefficient = 0.164, P < 0.01). Mean PASI scores of persons who used
      to consume alcohol and those who did not were comparable.(Z-test, z = -0.458, P =
      0.647). There was no association between severity of psoriasis and alcohol
      consumption.(chi(2) = 0.255, P = 0.613, Odds Ratio = 1.14, CI 0.696-1.866). There
      was no correlation between PASI scores and AUDIT scores (Spearman's correlation
      coefficient = 0.024, P > 0.05). CONCLUSIONS: Increased severity of psoriasis
      among adult males is associated with tobacco smoking, but not with alcohol use.

PMID- 24891653
TI  - Predictive factors for loco regional recurrence and distant metastasis following
      primary surgical treatment of cutaneous melanoma.
AB  - BACKGROUND: Cutaneous melanoma (CM) has a high propensity for regional and
      systemic spread. This is one of the largest series of CM reported from India.
      AIMS: To predict factors for loco regional recurrence (LRR) and distant
      metastasis in patients with CM primarily treated with surgery. STUDY DESIGN:
      Retrospective analysis of patient database at a tertiary care cancer center with
      evaluation of factors for LRR and distant metastasis for CM. MATERIALS AND
      METHODS: Data from 68 patients treated for CM between January 2006 and December
      2010 were reviewed. Data recorded included age, sex, symptoms, investigations,
      treatment given, histopathology, recurrence and follow-up. Patient factors, tumor
      factors, pathologic variables, and adjuvant treatment were investigated as
      predictors' of LRR and distant metastasis. RESULTS: Mean age of patients was 54
      years. Melanoma was more common in males (44). Tumor thickness > 4 mm was found
      in 43 patients. Lymph node involvement was found in 43 patients. Adjuvant
      radiotherapy was given in seven patients. At mean follow-up of 16.5 months, LRR
      was seen in 34 patients and distant metastasis in 28 patients. LRR and distant
      metastasis were more commonly found in females, age > 40 years, Clark's level IV
      and V, Breslow's depth > 4 mm, patients with lymph node involvement and extra
      capsular spread. CONCLUSION: The age, sex, site, thickness of lesion, involvement
      of lymph node, and extra-capsular spread were important factors in predicting LRR
      and distant metastasis. Distant metastasis was also more commonly found in
      patients with LRR.

PMID- 24891654
TI  - The spectrum of cutaneous infection in diabetic patients with hepatitis C virus
      infection: a single-center study from egypt.
AB  - CONTEXT: Hepatitis-C virus (HCV) infection and diabetes mellitus (DM) have a
      significant association with skin disorders. AIMS: The aim of this study was to
      assess the impact of HCV infection on the pattern of cutaneous infections among
      diabetic patients. METHODS AND MATERIAL: A prospective study included diabetic
      patients who attended Al-Hussein University hospital, Cairo during the period
      from 2008 to 2010. Patients were examined for skin infections, and investigated
      for HCV infection. STATISTICAL ANALYSIS USED: SPSS (version 11.5). RESULTS: The
      study included 163 patients (102 males and 61 females) with a mean age of 46.2 +/
      4.83 years. Ninety five patients (58.3%) were HCV+ve (group A) while 68 patients
      (41.8%) were HCV-ve (group B). Skin infections in group A included fungal
      (48.4%), viral (26.3%), bacterial (22.1%) and parasitic (3.2%) while in group B,
      the spectrum included bacterial (41.2%), fungal (39.7%), viral (11.7%) and
      parasitic (7.4%). Onychomycosis was the commonest infection in group A (25.2%)
      compared with folliculitis in group B (19.1%). Cutaneous infections in HCV+
      patients were more characterized by increased severity, aggressive course,
      resistance to treatment and rapid relapse. CONCLUSIONS: HCV infection has a
      significant impact in increasing and changing the spectrum of skin infections in
      diabetic patients. Severe and resistant infections in diabetics could be an
      important sign of HCV infection.

PMID- 24891655
TI  - Aeroallergen patch testing in patients of suspected contact dermatitis.
AB  - BACKGROUND: Aeroallergens are airborne substances present in the environment with
      the potential to trigger an allergic reaction in the respiratory tract, mucosae,
      or skin of susceptible individuals. The relevance of aeroallergens in the
      pathogenesis of atopic dermatitis has been reported by many investigators.
      However, very few studies have been conducted to investigate their role in the
      production of allergic contact dermatitis (ACD). AIMS: To determine the
      prevalence of aeroallergen patch test positivity in patients of suspected ACD and
      to study the clinical characteristics of patients testing positive with
      aeroallergens. MATERIALS AND METHODS: Patients presenting to our department with
      suspected contact allergy and undergoing patch testing with Indian Standard
      Series (ISS) between January 2010 and June 2011 were studied. After a detailed
      history and clinical examination, patients were patch tested with ISS and
      aeroallergen series. Based on the history and clinical suspicion, patients were
      additionally patch tested with 15% Parthenium. Prior tape stripping was done in
      some patients. RESULTS: Out of total 114 patients, 26 (22.8%) showed sensitivity
      to aeroallergen series. Parthenium was the commonest aeroallergen being positive
      in all 26 patients followed by Xanthium in two. None reacted to other allergens.
      Although positivity was more in patients with prior tape stripping, the
      difference was not statistically significant. CONCLUSION: Most common
      aeroallergen found to be positive in our study was Parthenium hysterophorus. In
      view of low positivity to other allergens, routine aeroallergen patch testing in
      patients with suspected contact dermatitis may not be necessary.

PMID- 24891656
TI  - Lichen planus: a clinical and immuno-histological analysis.
AB  - BACKGROUND: Direct immunofluorescence examination is an important technique in
      the diagnosis of cutaneous inflammatory disorders including lichen planus,
      especially in clinically and histopathological doubtful cases. OBJECTIVE: To
      study the diagnostic utility of intensity, number, and subtypes of positive
      immuno-reactants found in lichen planus. MATERIALS AND METHODS: A detailed
      analysis of clinical as well as immuno-histological features of lichen planus
      cases was carried out. RESULTS: The male to female ratio was 1:1.1. The largest
      number of patients was in 31-50 year age group. Itching was the most common
      presenting symptom. Papular lesions were seen in 53% cases. Remaining had
      hypertrophic (6), follicular (3) and mucosal (9) variants. Clinico-pathological
      discrepancies were observed in 3 patients. The characteristic histopathological
      changes including basal cell vacuolization, band-like lymphocytic infiltrate at
      dermo-epidermal junction were seen in all the biopsies while Civatte bodies were
      detected in 29% cases. The overall positive yield of direct immunofluorescence
      microscopy was 55%. Immune deposits at Civatte bodies and dermo-epidermal
      junction were detected in 47% and 8% of cases, respectively. Immunoglobulin M was
      the most common immunoreactant followed by immunoglobulin G. CONCLUSIONS: There
      was no correlation found between the number and intensity of Civatte bodies with
      clinical variants of disease and also between the number of positive
      immunoreactants and clinical severity of the disease. The frequency, number, and
      arrangement of Civatte bodies in clusters in the papillary dermis as well as
      multiple immunoglobulins deposition at the Civatte bodies on direct
      immunofluorescence of skin biopsies are important features distinguishing lichen
      planus from other interface dermatitis.

PMID- 24891657
TI  - A clinical and mycological study of dermatophytic infections.
AB  - BACKGROUND: Dermatophytoses refer to superficial fungal infection of keratinized
      tissues caused by keratinophilic dermatophytes. According to observations
      worldwide, dermatophytoses are the most common of the superficial fungal
      infections. It is common in tropics and may present in epidemic proportions in
      areas with high rates of humidity. Although common, the precise size of the
      problem defies measurement. AIMS: The present study was undertaken to assess the
      clinical profile of dermatophytic infection and to identify the species of fungi
      that are prevalent in this region. MATERIALS AND METHODS: A total of 100 patients
      clinically suspected for dermatophytoses were selected for the study. Direct
      microscopy in 10% potassium hydroxide (KOH) and culture was done in each case.
      RESULTS: Out of 100 patients, the maximum were seen in the age groups of 16-30
      years. Tinea corporis was the most common clinical type (44.3%) followed by tinea
      cruris (38.2%). Overall positivity by culture was 39% and by direct microscopy
      96%. CONCLUSION: Trichophyton rubrum was the predominant species isolated (67.5%)
      in all clinical types followed by Trichophyton mentagrophytes. Culturing the
      fungus may identify the species, but it is not essential for the diagnosis as it
      is not a sensitive test.

PMID- 24891658
TI  - Mycological pattern of dermatophytosis in and around shimla hills.
AB  - INTRODUCTION: Dermatophytosis is defined as the fungal infection of the skin,
      hair and nails by a group of keratinophillic fungi known as dermatophytes. AIMS
      AND OBJECTIVES: This study is an attempt to find out various species of
      dermatophytes in clinically suspected cases of dermatophytosis. MATERIALS AND
      METHODS: One hundred samples were subjected to direct microscopy by potassium
      hydroxide wet mount (KOH) and isolation on culture with Sabourauds dextrose agar.
      RESULTS: Out of these 80 (80%) samples were KOH positive while 20 (20%) were KOH
      negative. Overall culture positivity rate was 68%. Dermatophytosis was more
      common in males, the M:F ratio was 4:1. CONCLUSION: Total seven species were
      isolated on culture. Trichophyton rubrum (66.17%) was the commonest isolate
      followed by Trichophyton mentagrophytes (19.11%), Trichophyton violaceum (7.35%),
      Trichophyton tonsurans (2.94%) and one isolate each of Epidermophyton floccosum
      and Microsporum gypseum (1.47%).

PMID- 24891659
TI  - Dermatological Side Effects of Epidermal Growth Factor Receptor Inhibitors:
      'PRIDE' Complex.
AB  - Epidermal growth factor receptor (EGFR) inhibitor therapy has become the standard
      treatment for non-small cell lung cancer and head neck malignancy. This class of
      drug comprises EGFR inhibitors (erlotinib and gefitinib) and monoclonal antibody
      (cetuximab). Use of this class of drugs has been associated frequently with
      dermatological side effects termed as PRIDE complex-Papulopustules and/or
      paronychia, Regulatory abnormalities of hair growth, Itching, Dryness due to EGFR
      inhibitors. We hereby report the cutaneous side effects of EGFR inhibitor therapy
      in 15 patients of lung and head/neck cancer. The major clinical findings being
      acneiform eruption and severe xerosis of skin. Management of these dermatological
      adverse effects rarely requires discontinuation of targeted therapy and can be
      managed symptomatically. 

PMID- 24891661
TI  - Allergic Contact Dermatitis (Type IV Hypersensitivity) and Type I
      Hypersensitivity Following Aromatherapy with Ayurvedic Oils (Dhanwantharam
      Thailam, Eladi Coconut Oil) Presenting as Generalized Erythema and Pruritus with
      Flexural Eczema.
AB  - Herbal and Ayurvedic medications, believed to be "mild" and "natural" are usually
      sought as the first line of treatment before resorting to "stronger" allopathic
      medication. There are very few reports of adverse reactions to either topical
      and/or systemic Ayurvedic medications. Massage aromatherapy with ayurvedic oils
      plays an important role in alleviation of pain, but may cause allergic contact
      dermatitis. This is the second case report of allergic contact dermatitis to
      ayurvedic oil. 

PMID- 24891662
TI  - Familial reactive perforating collagenosis: a report of two cases.
AB  - Reactive perforating collagenosis (RPC) is a rare form of transepithelial
      elimination, in which genetically altered collagen is extruded through the
      epidermis. Of the acquired and inherited form, inherited form is extremely rare.
      Here, we present two cases of inherited form of RPC in a family. 

PMID- 24891660
TI  - Wolf's Isotopic Response: Report of a Case and Review of Literature.
AB  - "Wolf's isotopic response" refers to the occurrence of a new dermatosis at the
      site of previously healed dermatosis. A number of factors including viral,
      neural, vascular, and immunologic factors have been implicated in the causation
      of this peculiar response but none has been proven conclusively. Here, we report
      a case where lichen planus developed at the site of dermatofibrosarcoma
      protruberans that had been previously treated with surgery and radiotherapy. We
      also put forth a hypothesis on the genesis of isotopic response considering the
      above mentioned factors. 

PMID- 24891663
TI  - A case of reticulate acropigmentation of kitamura: dowling degos disease overlap
      with unusual clinical manifestations.
AB  - Reticulate hyperpigmentary disorders are a group of rare genetic pigmentary
      abnormalities which includes reticulate acropigmentation of Kitamura (RAPK),
      Dowling-Degos disease (DD), reticulate acropigmentation of Dohi (RAPD), Haber's
      syndrome, and Galli-Galli disease. A 25-year-old male presented with asymptomatic
      dark-colored lesions on his hands and feet with light-colored skin lesions
      involving the trunk since three years. Dermatological examination revealed
      hyperpigmented macules in a reticulate pattern involving the dorsa of the hands
      and feet, front and sides of the neck, axillae, periorbital region, and groin.
      Multiple pits were present over both palms, with breaks in dermatoglyphics. He
      also had multiple nonacne facial scars predominantly on the nose and malar areas.
      The patient had overlapping features of RAPK and DDD. In addition, he also had
      hypopigmented macules and acneiform facial scars. Such an overlap of features of
      reticulate pigmentation has not been previously reported in the literature. 

PMID- 24891664
TI  - Acquired Bilateral Nevus of ota-like Macules with Mucosal Involvement: A New
      Variant of Hori's Nevus.
AB  - Acquired bilateral nevus of Ota-like macules (ABNOM) or Hori's nevus, a rare form
      of acquired dermal melanocytoses, presents as bilateral facial blue-gray macules
      without ocular or mucosal involvement. This condition is mostly found in women of
      Asian descent and usually appears in the fourth or fifth decade of life.
      Pathogenesis is unknown, though few theories have been proposed. Effective
      treatment has been found to be achieved with pigment-specific lasers. Herein, we
      report a case of Hori's nevus with mucosal involvement. A 42-year-old male
      patient, presented to us with blue-gray discoloration on either side of his face,
      both eyes, and in the mouth since the age of one year. Histopathological
      examination showed clusters and singly dispersed pigmented melanocytes within the
      upper and mid-dermis regions. Special staining of melanocytes using Masson
      Fontana stain was positive. Diagnosis of Hori's nevus was made by correlating
      clinical and histopathological findings. Patient was informed of his treatment
      options, but refused treatment. A similar case of Hori's nevus with mucosal
      involvement has not been reported so far. 

PMID- 24891665
TI  - Retraction notice.

PMID- 24891666
TI  - Myxoinflammatory fibroblastic sarcoma: an uncommon tumour at an unusual site.
AB  - Myxoinflammatory fibroblastic sarcoma is a low grade sarcoma that is composed of
      a mixed inflammatory infiltrate along with spindled, epithelioid and bizarre
      appearing cells in a background of hyaline and myxoid zones. Seen affecting the
      distal extremities commonly, with an equal sex predilection, these tumors are
      rare and require an extensive immunohistochemical work up for proper diagnosis.
      They have a tendency to recur. 

PMID- 24891667
TI  - Varicella zoster with erythema multiforme in a young girl: a rare association.
AB  - Erythema multiforme (EM) is an acute, self-limited, mucocutaneous disorder
      regarded as a hypersensitivity reaction which is triggered by various factors
      like infection, drugs, and food. Infectious agents are considered to be a major
      cause of EM other than idiopathic cause. A young girl presented with fluid-filled
      lesions all over the body of 3 days duration with history of similar lesions with
      fever in her sibling 2 weeks prior to admission. This was followed by large fluid
      filled lesions with halo 3 days thereafter over the trunk, extremities suggesting
      target lesions of EM. The diagnosis was confirmed by cytology and positive
      serology. Varicella zoster virus (VZV) has rarely been reported as an etiological
      agent, despite its high incidence in childhood. VZV as an etiology of EM in a
      young girl has not been reported so far. This case was reported for its rare
      association of EM and varicella zoster and also for its rare presentation in a
      young girl. 

PMID- 24891668
TI  - Human demodex mite: the versatile mite of dermatological importance.

PMID- 24891669
TI  - Author's Reply.

PMID- 24891670
TI  - Radiation port cutaneous metastases: a further example of immunocompromised
      district.

PMID- 24891671
TI  - Author's Reply.

PMID- 24891672
TI  - A case of cutaneous squamous cell carcinoma arising in an actinic keratosis on
      the face in a centenarian woman successfully treated with surgery.

PMID- 24891673
TI  - Co-existence of Rheumatoid Arthritis, Vitiligo, and Bullous Pemphigoid as
      Multiple Autoimmune Syndrome.

PMID- 24891674
TI  - Nodular primary localized cutaneous amyloidosis in a patient with pulmonary
      sarcoidosis.

PMID- 24891675
TI  - Ocular myiasis with Basal cell carcinoma.

PMID- 24891676
TI  - Cutaneous myiasis in an infant with cerebral palsy.

PMID- 24891677
TI  - Imatinib mesylate-induced cutaneous rash masquerading as pityriasis rosea of
      gilbert.

PMID- 24891678
TI  - Retroauricular nodules in a post-renal transplant individual.

PMID- 24891679
TI  - Food hypersensitivity in patients over 14 years of age suffering from atopic
      dermatitis.
AB  - BACKGROUND: Patients suffering from atopic dermatitis often describe food
      hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic
      reactions to foods have been reported, but the data are scarce. AIMS AND
      OBJECTIVES: Evaluation of food hypersensitivity reactions in patients suffering
      from atopic dermatitis. MATERIALS AND METHODS: The dermatological examination was
      performed in patients of age 14 years and above and the detailed history was
      taken concerning the food hypersensitivity. RESULTS: A total of 228 patients were
      examined-72 men, 156 women, average age 26.2 (SD 9.5) years. The food
      hypersensitivity reactions were recorded in 196 patients from 228 (86%), no
      reactions were recorded in 32 patients (24%). Foods with the most often recorded
      reactions are: Nuts (in 35% of patients), tomatoes (in 20%), and kiwi (in 17,
      5%), apples and spices (in 16%), tangerines and oranges (in 15%), capsicum (in
      13%), fishes (in 12%), celery (in 9%), and chocolate (in 7%). CONCLUSION: Food
      hypersensitivity reactions are recorded in 86% of patients suffering from atopic
      dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the
      majority of patients suffering from atopic dermatitis.

PMID- 24891680
TI  - Comorbidity of leishmania major with cutaneous sarcoidosis.
AB  - BACKGROUND: leishmaniasis infection might manifest as sarcoidosis; on the other
      hand, some evidences propose an association between sarcoidosis and
      leishmaniasis. Most of the times, it is impossible to discriminate idiopathic
      sarcoidosis from leishmaniasis by conventional histopathologic exam. AIM: We
      performed a cross-sectional study to examine the association of sarcoidosis with
      leishmaniasis in histopathologically diagnosed sarcoidal granuloma biopsy samples
      by polymerase chain reaction (PCR). MATERIALS AND METHODS: We examined paraffin
      embedded skin biopsy samples obtained from patients with clinical and
      histopathological diagnosis as naked sarcoidal granuloma, referred to Skin
      Research Center of Shaheed Beheshti Medical University from January 2001 to March
      2010, in order to isolate Leishmania parasite. The samples were reassessed by an
      independent dermatopathologist. DNA extracted from all specimens was analyzed by
      the commercially available PCR kits (DNPTM Kit, CinnaGen, Tehran, Iran) to detect
      endemic Leishmania species, namely leishmania major (L. major). RESULTS: L. major
      was positive in PCR of Eight out of twenty-five examined samples. CONCLUSION:
      Cutaneous leishmaniasis may be misinterpreted as sarcoidosis; in endemic areas,
      when conventional methods fail to detect Leishmania parasite, PCR should be
      utilized in any granulomatous skin disease compatible with sarcoidosis,
      regardless of the clinical presentation or histopathological interpretation.

PMID- 24891681
TI  - Safety and efficacy of low-dose isotretinoin in the treatment of moderate to
      severe acne vulgaris.
AB  - BACKGROUND: Isotretinoin is indicated for moderate to severe cases of acne which
      are unresponsive to conventional therapy. The classical recommended dose is 0.5
      to 1.0 mg/kg/day. As the side effects are dose related, low-dose isotretinoin
      therapy for acne is an attractive option; however, but little data exists on the
      safety and efficacy of this strategy. MATERIALS AND METHODS: In this prospective,
      non-comparative study, 50 participants, both male and female, having moderate to
      severe acne vulgaris were enrolled and treated with isotretinoin at a dose of 20
      mg/day (approximately 0.3-0.4 mg/kg/day), for a period of 3 months. Participants
      were evaluated by means of clinical and laboratory investigations before starting
      isotretinoin. Investigations were repeated at the end of the first and third
      months following completion of treatment, and participants were followed up for 6
      months to look for any relapse. RESULTS: At the end of the treatment, very good
      results were observed in 90% of participants. Cheilitis was the most common among
      the side effects observed and was seen in 98% of the participants. One
      participant developed vitiligo as a side effect, which is a new finding, and has
      not reported in literature before. Elevated serum lipid levels were observed in
      6% of the participants, and relapse occurred in 4% of the participants over a 6
      month follow up period. CONCLUSION: Three months of treatment with low-dose
      isotretinoin (20 mg/day) was found to be effective in the treatment of moderate
      to severe acne vulgaris, with a low incidence of serious side effects. This dose
      also was more economical than the higher doses.

PMID- 24891682
TI  - Multiple recurrences in pityriasis rosea - a case report with review of the
      literature.
AB  - Pityriasis rosea (PR) is a common benign cutaneous disorder of children and young
      adults. The etiology of this condition is still unknown. Despite the common
      occurrence, second episode of PR is noted only in 1-3% of the cases. Multiple
      recurrences (three or more episodes) are extremely uncommon and to the best of
      our knowledge, only few patients have been reported in the literature. Due to the
      benign nature of the disease, these recurrences may be either underestimated or
      unreported. Till date, there are no predisposing factors identified for the
      occurrence of these multiple episodes. We report a case of pityriasis rosea in an
      11-years-old male with three episodes with review of the literature. 

PMID- 24891683
TI  - Adult-onset unilateral disabling pansclerotic morphea.
AB  - Disabling pansclerotic morphea (DPM) is a rare, severe, and mutilating form of
      morphea, involving the dermis, subcutaneous tissue, fat, muscle, and even bone.
      It is usually seen before the age of 14 years, with the patient complaining of
      arthralgia and stiffness at the time of onset. We report a case of unilateral
      adult-onset DPM with sparing of the face. Within a few months of onset, painful
      contracture deformities of the hand, elbow, and shoulder joints developed,
      impairing the patient's normal daily activities. We are reporting this case
      because of the unusual presentation: DPM in an adult, with history of trauma in
      childhood and rapid onset of complications, is rare. 

PMID- 24891684
TI  - Livedo reticularis due to pellagra in a two year old child.
AB  - A two-year-old girl child was admitted with complaints of diarrhoea of one week
      duration in the paediatric ward. She was referred to the skin OPD for gradually
      progressive skin rashes on both lower limbs noticed since two days.
      Dermatological examination revealed finding of livedo reticularis. Dietary
      history revealed maize forming a significant portion of the child's diet since
      the age of nine months. The child was treated with a course of Niacin in the form
      of Nicotinamide 50 mg twice a day for 4 weeks and the parents were advised not to
      give her maize in the diet. The skin lesions and diarrhoea regressed in duration
      of two weeks. This is probably the first time that a case of pellagra causing
      livedo is being reported, that too in a child. 

PMID- 24891685
TI  - Peyronie's Disease Treated with Oral Weekly Dexamethasone and Continuous Low-dose
      Cyclophosphamide.

PMID- 24891686
TI  - Type VIII - Ehlers Danlos Syndrome with cafe-au-lait macules: A Rare Variant.

PMID- 24891687
TI  - Screening of celiac disease in children with alopecia areata.

PMID- 24891688
TI  - Congenital myofibroma mimicking an infantile hemangioma in an infant.

PMID- 24891689
TI  - Progressive symmetric erythrokeratoderma with unusual associations.

PMID- 24891690
TI  - Linear porokeratosis: an unusual presentation.

PMID- 24891691
TI  - A 68 year old male with abdominal pain, anorexia, and facial skin pigmentation.

PMID- 24891692
TI  - Moving psychopharmacological drug development to the developing world.

PMID- 24891693
TI  - Position statement and guideline on media coverage of suicide.

PMID- 24891694
TI  - Gambling addiction in India: Should psychiatrists care?

PMID- 24891695
TI  - Intellectual disability in India: Charity to right based.

PMID- 24891696
TI  - Diagnostic and Statistical Manual-5 and dementia: Fine print, finer points.

PMID- 24891697
TI  - Forensic psychiatry in India: The road ahead.

PMID- 24891699
TI  - Emotion.

PMID- 24891700
TI  - Walk your life path.

PMID- 24891701
TI  - Impact evaluation of the community mental health program at habra.
AB  - BACKGROUND: It is a well-known fact that there is a huge gap between mental
      health service availability and needs of people in the community. Community
      Mental Health Program (CMHP) appears as a solution for it. Paripurnata (a non
      governmental organization) has been running a CMHP at Habra, West Bengal, India
      since 2000. Since 2005 a psychiatric out-patient department is functioning and
      community work is focused on capacity building of different stakeholders. Several
      awareness camps, community preparedness workshops have been organized. However,
      the work is yet to be consolidated with initiatives from the community. It has to
      be facilitated more with an objective analysis of the situation. The need of the
      hour is to assess the previous work. So an evaluation study was planned. AIMS:
      The primary aim of the following study is to assess the impact of the CMHP on the
      local population and secondary aim is to evaluate that what extent the CMHP have
      been able to prepare them to take responsibility of the CMHP as a whole.
      MATERIALS AND METHODS: Using systematic random sampling method 1486 respondents
      were selected and data collect using a questionnaire. In-depth interviews, focus
      group discussions, participant's observation and secondary data sources were also
      used. Inferences drown based on above all data sources. RESULTS AND CONCLUSION:
      Two-third of the studied population and more so in the target area expressed that
      the community can take responsibility of running their own CMHPs. Though, the
      larger population of them is still not acquainted with the activities of the
      CMHP, the program deserves support to sustain.

PMID- 24891698
TI  - Psychiatry and music.
AB  - Vocal and/or instrumental sounds combined in such a way as to produce beauty of
      form, harmony and expression of emotion is music. Brain, mind and music are
      remarkably related to each other and music has got a strong impact on psychiatry.
      With the advent of music therapy, as an efficient form of alternative therapy in
      treating major psychiatric conditions, this impact has been further strengthened.
      In this review, we deliberate upon the historical aspects of the relationship
      between psychiatry and music, neural processing underlying music, music's
      relation to classical psychology and psychopathology and scientific evidence base
      for music therapy in major psychiatric disorders. We highlight the role of Indian
      forms of music and Indian contribution to music therapy. 

PMID- 24891702
TI  - Psychiatric morbidity among prisoners.
AB  - BACKGROUND: There is a considerable lack of scientific estimate of psychiatric
      morbidity among Indian prisoners. OBJECTIVE: The objective of the following study
      is to study the prevalence of psychiatric morbidity among prisoners. SETTINGS AND
      DESIGN: A cross-sectional study at District Jail, Kozhikode, Kerala. MATERIALS
      AND METHODS: A total of 255 prisoners who were inmates during the period from mid
      April to mid-July 2011 participated in the study. The study subjects included
      both male and female remand or convict prisoners. Socio-demographic data,
      clinical history and criminological history were collected from each individual.
      Psychiatric morbidity was assessed using MINI-Plus. STATISTICAL ANALYSIS: Done by
      using SPSS version 16 (SPSS Inc, Chicago, USA). RESULTS: A total of 175 subjects
      (68.6%) had a current mental illness. Substance use disorder was the most common
      diagnosis (47.1%). Antisocial personality disorder was diagnosed in 19.2%,
      adjustment disorder in 13.7%, mood disorder in 4.3% and psychosis in another 6.3%
      of prisoners. A high rate of a current psychiatric disorder was seen in male
      (69.7%) prisoners. A significant association was noticed for the different nature
      of crimes with psychiatric diagnoses and previous imprisonment. Nearly 4% of
      prisoners reported a moderate to high suicide risk. CONCLUSION: Mental health
      problems among prisoners were quite high. Mentally ill prisoners are at high risk
      for repeated incarceration. The increased rate of psychiatric disorders should be
      a concern for mental health professionals and the policy makers.

PMID- 24891703
TI  - Prevalence of psychiatric morbidity among urban elderlies: Lucknow elderly study.
AB  - BACKGROUND: Paucity of systematic studies in elderly mental health in an aging
      population is an urgent need, which is required to address services and planning
      issues for health. AIM: The present study aims to investigate the distribution of
      physical, neuropsychiatric, and cognitive disorders of a community sample of
      elderlies with certain socioeconomic data. MATERIALS AND METHODS: A door-to-door
      household survey was conducted to identify houses with elderlies (>=55 years) in
      two urban localities of Lucknow. Mini mental state examination (MMSE), Survey
      Psychiatric Assessment Schedule (SPAS)/Mood Disorder Questionnaire (MDQ) and
      physical and neurological examination were used for screening all consenting
      elderlies. MMSE positive participants were assessed on Cambridge Mental Disorders
      of the Elderly Examination-Revised for diagnosis of cognitive disorders; SPAS/MDQ
      positives were assessed on Schedule for Clinical Assessment in Neuropsychiatry
      based clinical interview for diagnosis of neuropsychiatric disorders other than
      cognitive disorders (using ICD-10 criteria). Routine and indicated
      laboratory/radiological investigations on all and on MMSE/SPAS (organic section)
      positive/physically ill participants respectively were done to confirm organic
      and/or physical illness. Only percentages were calculated to find the
      distribution of morbidity. RESULTS: The sample had proportionate age structure as
      that of the surveyed population and had balanced gender representation in each
      age deciles. Prevalence of neuropsychiatric disorders (with/without
      comorbidities) was 11.8% in the elderlies (60 years and above) highest being in
      the 60-69 years age group. Being women and of lower socioeconomic status was more
      commonly associated with a neuropsychiatric diagnosis. 7.6% of the elderlies had
      cognitive impairment. Overall findings suggest a prevalence rate of 17.34% of
      total psychiatric morbidity among elderlies. A significant number had comorbid
      physical illness diagnoses. CONCLUSION: More than half the elderlies had some
      diagnosable physical or mental ailment. The study familiarizes us to the
      significant amount of physical and psychiatric comorbidity in the particular age
      group. About one-fifth was found to suffer from psychiatric morbidity, which any
      health services for the elderly should be oriented towards.

PMID- 24891704
TI  - A study of mental health status of men who have sex with men in Ahmedabad city.
AB  - BACKGROUND: Men who have sex with men (MSM), a unique group of people, feel, and
      believe they will face hardships in society once their identity is disclosed, but
      this does not deter them from dressing and behaving like the opposite sex in
      public life or fighting for their rights. OBJECTIVES: To study the mental health
      status of MSM and their determinants. MATERIALS AND METHODS: Descriptive cross
      sectional study was conducted among 410 MSM in the drop in centers of non
      governmental organization working for MSM in Ahmedabad city through purposive
      sampling. RESULTS: Prevalence of psychiatric morbidity was 52.9%. The mean score
      obtained in anxiety/insomnia subscale (5.4 +/- 4.2) and severe depression (5.4 +/
      4.6) was higher than other two subscale somatic symptoms (4.0 +/- 3.2) and
      social dysfunction symptoms (4.6 +/- 3.8). Among General Health Questionnaire 28
      questions, "more MSM had a more than usual feeling" that they are "getting
      difficulty in staying asleep once you are off", "lost much sleep over worry",
      "been getting edgy and bad tempered", "felt constantly under strain", "been
      feeling nervous and strung-up all time." Prevalence of psychiatric morbidity is
      more in never married MSM and also in less educated MSM. MSM with sexually
      transmitted infection (STI) symptoms suffer from psychiatric illness more than
      MSM who didn't have STI symptoms. CONCLUSION: Various determinants like partner
      characteristic, presence of STI symptoms, marital status, and living arrangement
      affect the mental health of MSM.

PMID- 24891705
TI  - The clinical profile of mentally retarded children in India and prevalence of
      depression in mothers of the mentally retarded.
AB  - BACKGROUND: Mental retardation (MR) has a varied phenomenology in different parts
      of the world. While studying MR, psychological issues of caretakers are equally
      relevant. A study to investigate the phenomenology of MR in Indian children and
      the prevalence of depression in their mothers was planned in a teaching institute
      in Madhya Pradesh with an attached tertiary care hospital. OBJECTIVES: The
      objective of the following study is to study the clinical profile of mentally
      retarded children in the study sample, prevalence of depression in the mothers
      and investigate various factors affecting it. STUDY DESIGN: A cross-sectional
      study. MATERIALS AND METHODS: A total of 60 patients diagnosed as MR were
      included in the study. Objective data was collected in a special proforma and
      mothers of these individuals were subjected to evaluation with Beck's Anxiety
      Inventory and the 17 item Hamilton Rating Scale for Depression. RESULTS: The mean
      age of patients in the sample was 11.6 years, had received an average of 2.42
      years of schooling, mean age at diagnosis of MR was 6.5 years and their mean IQ
      was 53. Out of the total 60 patients, 88% of the patients had significant co
      morbidities. The prevalence of depression in mothers was 85% and it was more in
      mothers of, the ones with significant co-morbidities (OR = 2.67), severer forms
      of retardation and with higher levels of anxiety in the mother. CONCLUSIONS:
      Prevalence of depression in mothers of mentally retarded children in India seems
      to be much greater than those reported from studies around the world. Medical
      services offered to the mentally retarded should move from an individual level to
      the family level, especially toward the mothers, who are the main caretakers.
      Counseling services, treatment if required and regular screening of mothers of
      the mentally retarded should be included in the protocol for management of mental
      retardation.

PMID- 24891706
TI  - Delirium: Predictors of delay in referral to consultation liaison psychiatry
      services.
AB  - OBJECTIVE: To evaluate the predictors of delay in psychiatry referral for
      patients with delirium. MATERIALS AND METHODS: The consultation liaison
      psychiatry registry and case notes of 461 patients referred to psychiatry
      consultation liaison services and diagnosed as having delirium were reviewed.
      Data pertaining to sociodemographic variables, clinical variables, Delirium
      Rating Scale-Revised 98 version, etiologies associated with delirium were
      extracted. RESULTS: Older age, presence of and higher severity of sleep
      disturbance, presence of and higher severity of motor retardation, presence of
      visuospatial disturbances, presence of fluctuation of symptoms, being admitted to
      medical ward/medical intensive care units, and absence of comorbid axis-1
      psychiatry diagnoses were associated with longer duration of psychiatric referral
      after the onset of delirium. Of these only four variables (presence of sleep
      disturbance, presence of motor retardation, being admitted to medical ward
      intensive care units and absence of comorbid axis-1 psychiatry diagnoses) were
      associated with longer duration of psychiatric referral in the regression
      analysis. CONCLUSION: The variables associated with delay in psychiatry referral
      for delirium suggest that there is a need to improve the understanding of the
      physicians and surgeons about the signs and symptoms, risk factors, and
      prognostic factors of delirium.

PMID- 24891707
TI  - Pharmacovigilance for psychiatrists: An introduction.

PMID- 24891708
TI  - Mistaken gender identity in non-classical congenital adrenal hyperplasia.
AB  - Gender identity is the sense of belonging that one feels for a particular sex
      psychologically and socially, independent of one's biological sex. There is much
      less systematic data on gender identity in females with congenital adrenal
      hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of
      gender identity disorder. 

PMID- 24891709
TI  - A rare case of fish odor syndrome presenting as depression.
AB  - A young lady presents to the psychiatry out-patient department with depressive
      symptoms. Evaluation revealed long standing stressor in the form of a foul odor
      emanating from her body and over a period of time resulting in social withdrawal
      and depression with significant impairment of day-to-day functioning. A diagnosis
      of trimethylaminurea (fish odor syndrome) and adjustment disorder was arrived at.
      Careful empathetic handling with psychoeducation, behavioral and cognitive
      counseling and a short course of antidepressants helped her improve significantly
      with return to almost normal functioning. 

PMID- 24891710
TI  - A case of psychosis due to Fahr's syndrome and response to behavioral
      disturbances with risperidone and oxcarbazepine.
AB  - Calcification of basal ganglia or Fahr's syndrome is a rare disease characterized
      by bilateral and symmetrical intracranial deposition of calcium mainly in
      cerebral basal ganglia. Motor and neuropsychiatric symptoms are prominent
      features. We report a case presented with a few motor symptoms, features of
      delirium and prominent psychiatric symptoms (disorganized behavior) predominantly
      evident after the improvement in delirium. Radiological findings were suggestive
      of bilateral basal ganglia calcification. Parathyroid hormone levels were low
      with no significant findings in other investigations and negative family history.
      Patient showed significant improvement in behavioral disturbances with
      risperidone, low dose of lorazepam, oxcarbazepine, and memantine. 

PMID- 24891712
TI  - Filicide as a part of extended suicide: An experience of psychotherapy with the
      survivor.
AB  - The tragedy of maternal filicide and extended suicides has occurred throughout
      history. Maternal filicide-suicide perpetrators most often suffer from
      depression, suicidality, or psychosis. Interventions in such cases are not
      commonly reported in the psychiatric settings, and the components of
      psychotherapeutic approach and its efficacy are also not known. Here we present a
      long-term therapy carried out with a 36-year-old married lady, with the
      complaints of low mood, suicidal ideation, severe guilt feelings, and depressive
      cognitions. There was positive family history of depression, past history of
      dysthymia, suicidal attempt, and severe marital discord. Therapy was carried out
      for a period of 9 months with follow-up for 4 years and addressed existential
      issues and grief with the components of existential therapy, grief therapy,
      narratives, religious beliefs, and interpersonal acceptance. The case highlights
      the need for blending of multiple approaches to meet the challenges such cases
      can pose. 

PMID- 24891711
TI  - Clozapine and cancer treatment: Adding to the experience and evidence.
AB  - The judiciousness of the use of clozapine in patients with schizophrenia in
      clinical practice is brought to an even sharper focus when it has to be used in
      combination with other agents that cause myelosuppression, for example,
      chemotherapy and radiation treatment. There are a few references till date
      illustrating the combination of clozapine and chemotherapy and/or radiation
      therapy. To the best of our knowledge, such a case has not been reported from
      India. We report the case of a 39-year-old gentleman with a diagnosis of
      schizophrenia, remaining psychiatrically stable on clozapine, who underwent
      combination treatment of chemotherapy and radiotherapy for the treatment of
      cancer of the tongue in a tertiary care oncology centre in India. 

PMID- 24891713
TI  - Extrapyramidal side effects with low doses of amisulpride.
AB  - Amisulpride, the newly introduced antipsychotic in India, is claimed to be
      effective in both positive and negative symptom schizophrenia and related
      disorders, though it has little or no action on serotonergic receptors. Limbic
      selectivity and lower striatal dopaminergic receptor binding capacity causes very
      low incidence of EPS. But, in clinical practice, we are getting EPS with this
      drug even at lower doses. We have reported three cases of akathisia, acute
      dystonia, and drug-induced Parkinsonism with low doses of amisulpride. So, we
      should keep this side effect in mind when using amisulpride. In fact, more
      studies are required in our country to find out the incidence of EPS and other
      associated mechanism. 

PMID- 24891714
TI  - Rapid, illegible handwriting as a symptom of obsessive-compulsive disorder.
AB  - This is a case report of a 13 year male child who had co-morbid OCD and
      trichotillomania. On evaluation, he had rapid, illegible handwriting as a symptom
      of OCD, which has hitherto not been reported. 

PMID- 24891715
TI  - Treatment of the mentally ill in the Chola Empire in 11(th) -12(th) centuries AD:
      A study of epigraphs.
AB  - The paper deals with the epigraphs of the Chola emperors Veera Rajendra Deva
      (1063-1069 AD) and Raja Raja III (1216-1256 AD), found at the temples of
      Thirumukkudal and Vedaranyam, with emphasis on the treatment given to the
      residents of the attached hospitals with special reference to treatment of mental
      disorders. 

PMID- 24891716
TI  - Rimonabant-induced depression in schizophrenia.

PMID- 24891717
TI  - Addiction to lizard: A rare case report.

PMID- 24891718
TI  - Relevance of parapsychology in psychiatric practice: Response to Dr. R. C.
      Jiloha's comments.

PMID- 24891719
TI  - Relevance of parapsychology in psychiatric practice: Response to Dr. R. C.
      Jiloha's comments.

PMID- 24891720
TI  - Methodological considerations in studying psycho-social aspects of suicide.

PMID- 24891721
TI  - A fresh look at homosexuality.

PMID- 24891722
TI  - The Influence of Dimensionality on the Rate of Diffusive Escape From an Energy
      Well.
AB  - A commonly used idealization when describing separation of a chemical bond
      between molecules is that of an energy well which prescribes the dependence of
      energy of interaction between the molecules in terms of a reaction coordinate.
      The energy difference between the peak to be overcome and the root of the well is
      the so-called activation energy, and the overall shape of the well dictates the
      kinetics of separation through a constitutive assumption concerning transport. An
      assumption tacit in this description is that the state of the bond evolves with
      only a single degree of freedom-the reaction coordinate-as the system explores
      its energy environment under random thermal excitation. In this discussion we
      will consider several bonds described by one and the same energy profile. The
      cases differ in that the energy profile varies along a line extending from the
      root of the well in the first case, along any radial line in a plane extending
      from the root of the well in a second case, and along any radial line in space
      extending from the root of the well in a third case. To focus the discussion we
      determine the statistical rate of escape of states from the well in each case,
      requiring that the profile of the well is the same in all three cases. It is
      found that the rates of escape each depend exponentially on the depth of the well
      but that the coefficients of the exponential vary with depth of the well
      differently in the three cases considered.

PMID- 24891724
TI  - A Two-Scale Computational Model of pH-Sensitive Expansive Porous Media.
AB  - We propose a new two-scale model to compute the swelling pressure in colloidal
      systems with microstructure sensitive to pH changes from an outer bulk fluid in
      thermodynamic equilibrium with the electrolyte solution in the nanopores. The
      model is based on establishing the microscopic pore scale governing equations for
      a biphasic porous medium composed of surface charged macromolecules saturated by
      the aqueous electrolyte solution containing four monovalent ions [Formula: see
      text]. Ion exchange reactions occur at the surface of the particles leading to a
      pH-dependent surface charge density, giving rise to a nonlinear Neumann condition
      for the Poisson-Boltzmann problem for the electric double layer potential. The
      homogenization procedure, based on formal matched asymptotic expansions, is
      applied to up-scale the pore-scale model to the macroscale. Modified forms of
      Terzaghi's effective stress principle and mass balance of the solid phase,
      including a disjoining stress tensor and electrochemical compressibility, are
      rigorously derived from the upscaling procedure. New constitutive laws are
      constructed for these quantities incorporating the pH-dependency. The two-scale
      model is discretized by the finite element method and applied to numerically
      simulate a free swelling experiment induced by chemical stimulation of the
      external bulk solution.

PMID- 24891723
TI  - Highly Nonlinear Solitary Waves for the Assessment of Dental Implant Mobility.
AB  - In this paper we present a noninvasive technique based on the propagation of
      highly nonlinear solitary waves (HNSWs) to monitor the stability of dental
      implants. HNSWs are nondispersive mechanical waves that can form and travel in
      highly nonlinear systems, such as one-dimensional chains of spherical particles.
      The technique is based on the hypothesis that the mobility of a dental implant
      affects certain characteristics of the HNSWs reflected at the interface between a
      crystal-based transducer and the implant. To validate the research hypothesis we
      performed two experiments: first we observed the hydration of commercial plaster
      to simulate at large the osseointegration process that occurs in the oral
      connective tissue once a dental-endosteal threaded implant is surgically
      inserted; then, we monitored the decalcification of treated bovine bones immersed
      in an acid bath to simulate the inverse of the osseointegration process. In both
      series, we found a good correlation between certain characteristics of the HNSWs
      and the stiffness of the material under testing.

PMID- 24891726
TI  - Analytical Study of Two Pin-Loaded Holes in Unidirectional Fiber-Reinforced
      Composites.
AB  - The objective of this paper is to investigate the effects of geometrical
      parameters such as the edge distance-to-hole diameter ratio {e/d}, plate width-to
      hole diameter ratio {w/d}, and the distance between two holes-to-hole diameter
      ratio {l/d} on stress distribution in a unidirectional composite laminate with
      two serial pin-loaded holes, analytically and numerically. It is assumed that all
      short and long fibers lie in one direction while loaded by a force po at
      infinity. To derive differential equations based on a shear lag model, a
      hexagonal fiber-array model is considered. The resulting pin loads on composite
      plate are modeled through a series of spring elements accounting for pin
      elasticity. The analytical solutions are, moreover, compared with the detailed 3D
      finite element values. A close match is observed between the two methods. The
      presence of the pins on shear stress distribution in the laminate is also
      examined for various pin diameters.

PMID- 24891725
TI  - Tortuosity and the Averaging of Microvelocity Fields in Poroelasticity.
AB  - The relationship between the macro- and microvelocity fields in a poroelastic
      representative volume element (RVE) has not being fully investigated. This
      relationship is considered to be a function of the tortuosity: a quantitative
      measure of the effect of the deviation of the pore fluid streamlines from
      straight (not tortuous) paths in fluid-saturated porous media. There are
      different expressions for tortuosity based on the deviation from straight pores,
      harmonic wave excitation, or from a kinetic energy loss analysis. The objective
      of the work presented is to determine the best expression for tortuosity of a
      multiply interconnected open pore architecture in an anisotropic porous media.
      The procedures for averaging the pore microvelocity over the RVE of poroelastic
      media by Coussy and by Biot were reviewed as part of this study, and the
      significant connection between these two procedures was established. Success was
      achieved in identifying the Coussy kinetic energy loss in the pore fluid approach
      as the most attractive expression for the tortuosity of porous media based on
      pore fluid viscosity, porosity, and the pore architecture. The fabric tensor, a
      3D measure of the architecture of pore structure, was introduced in the
      expression of the tortuosity tensor for anisotropic porous media. Practical
      considerations for the measurement of the key parameters in the models of Coussy
      and Biot are discussed. In this study, we used cancellous bone as an example of
      interconnected pores and as a motivator for this study, but the results achieved
      are much more general and have a far broader application than just to cancellous
      bone.

PMID- 24891727
TI  - Analytical Study of a Pin-Loaded Hole in Unidirectional Laminated Composites With
      Triangular and Circular Fibers.
AB  - The problem of stress concentrations in the vicinity of pin-loaded holes is of
      particular importance in the design of multilayered composite structures made of
      triangular or circular glass fibers. It is assumed that all of the fibers in the
      laminate lie in one direction while loaded by a force p0 at infinity, parallel to
      the direction of the fibers. According to the shear lag model, equilibrium
      equations are derived for both types of fibers. A rectangular arrangement is
      postulated in either case. Upon the proper use of boundary and bondness
      conditions, stress fields are derived within the laminate, along with the
      surrounding pinhole. The analytical results are compared to those of the finite
      element values. A very good agreement is observed between the two methods.
      According to the results, composite structures made of triangular glass fibers
      result in lower values of stress concentrations around the pin, as opposed to
      those of circular glass fibers.

PMID- 24891728
TI  - Modeling of Interior Ballistic Gas-Solid Flow Using a Coupled Computational Fluid
      Dynamics-Discrete Element Method.
AB  - In conventional models for two-phase reactive flow of interior ballistic, the
      dynamic collision phenomenon of particles is neglected or empirically simplified.
      However, the particle collision between particles may play an important role in
      dilute two-phase flow because the distribution of particles is extremely
      nonuniform. The collision force may be one of the key factors to influence the
      particle movement. This paper presents the CFD-DEM approach for simulation of
      interior ballistic two-phase flow considering the dynamic collision process. The
      gas phase is treated as a Eulerian continuum and described by a computational
      fluid dynamic method (CFD). The solid phase is modeled by discrete element method
      (DEM) using a soft sphere approach for the particle collision dynamic. The model
      takes into account grain combustion, particle-particle collisions, particle-wall
      collisions, interphase drag and heat transfer between gas and solid phases. The
      continuous gas phase equations are discretized in finite volume form and solved
      by the AUSM+-up scheme with the higher order accurate reconstruction method.
      Translational and rotational motions of discrete particles are solved by explicit
      time integrations. The direct mapping contact detection algorithm is used. The
      multigrid method is applied in the void fraction calculation, the contact
      detection procedure, and CFD solving procedure. Several verification tests
      demonstrate the accuracy and reliability of this approach. The simulation of an
      experimental igniter device in open air shows good agreement between the model
      and experimental measurements. This paper has implications for improving the
      ability to capture the complex physics phenomena of two-phase flow during the
      interior ballistic cycle and to predict dynamic collision phenomena at the
      individual particle scale.

PMID- 24891729
TI  - Analytical Solution for Whirling Speeds and Mode Shapes of a Distributed-Mass
      Shaft With Arbitrary Rigid Disks.
AB  - The purpose of this paper is to present an approach for replacing the effects of
      each rigid disk mounted on the spin shaft by a lumped mass together with a
      frequency-dependent equivalent mass moment of inertia so that the whirling motion
      of a rotating shaft-disk system is similar to the transverse free vibration of a
      stationary beam and the technique for the free vibration analysis of a stationary
      beam with multiple concentrated elements can be used to determine the forward and
      backward whirling speeds, along with mode shapes of a distributed-mass shaft
      carrying arbitrary rigid disks. Numerical results reveal that the characteristics
      of whirling motions are significantly dependent on the slopes of the associated
      natural mode shapes at the positions where the rigid disks are located.
      Furthermore, the results obtained from the presented analytical method and those
      obtained from existing literature or the finite element method (FEM) are in good
      agreement.

PMID- 24891730
TI  - Distribution and evolutionary impact of wolbachia on butterfly hosts.
AB  - Wolbachia are maternally inherited endosymbiotic alpha-proteobacteria found in
      terrestrial arthropods and filarial nematodes. They are transmitted vertically
      through host cytoplasm and alter host biology by inducing various reproductive
      alterations, like feminization, parthenogenesis, male killing (MK) and
      cytoplasmic incompatibility. In butterflies, some effects especially MK and sperm
      egg incompatibility are well established. All these effects skew the sex ratio
      towards female and subsequently favor the vertical transmission of Wolbachia.
      Some of the insects are also infected with multiple Wolbachia strains which may
      results in some complex phenomenon. In the present review the potential of
      Wolbachia for promoting evolutionary changes in its hosts with emphasis on recent
      advances in interactions of butterfly-Wolbachia is discussed. In addition to
      this, strain diversity of Wolbachia and its effects on various butterfly hosts
      are also highlighted. 

PMID- 24891732
TI  - Ecobiotechnological strategy to enhance efficiency of bioconversion of wastes
      into hydrogen and methane.
AB  - Vegetable wastes (VW) and food wastes (FW) are generated in large quantities by
      municipal markets, restaurants and hotels. Waste slurries (250 ml) in 300 ml BOD
      bottles, containing 3, 5 and 7 % total solids (TS) were hydrolyzed with bacterial
      mixtures composed of: Bacillus, Acinetobacter, Exiguobacterium, Pseudomonas,
      Stenotrophomonas and Sphingobacterium species. Each of these bacteria had high
      activities for the hydrolytic enzymes: amylase, protease and lipase. Hydrolysate
      of biowaste slurries were subjected to defined mixture of H2 producers and
      culture enriched for methanogens. The impact of hydrolysis of VW and FW was
      observed as 2.6- and 2.8-fold enhancement in H2 yield, respectively. Direct
      biomethanation of hydrolysates of VW and FW resulted in 3.0- and 1.15-fold
      improvement in CH4 yield, respectively. A positive effect of hydrolysis was also
      observed with biomethanation of effluent of H2 production stage, to the extent of
      1.2- and 3.5-fold with FW and VW, respectively. The effective H2 yields were 17
      and 85 l/kg TS fed, whereas effective CH4 yields were 61.7 and 63.3 l/kg TS fed,
      from VW and FW, respectively. This ecobiotechnological strategy can help to
      improve the conversion efficiency of biowastes to biofuels. 

PMID- 24891733
TI  - Beneficial Effect of Acetic Acid on the Xylose Utilization and Bacterial
      Cellulose Production by Gluconacetobacter xylinus.
AB  - In this work, acetic acid was found as one promising substrate to improve xylose
      utilization by Gluconacetobacter xylinus CH001. Also, with the help of adding
      acetic acid into medium, the bacterial cellulose (BC) production by G. xylinus
      was increased significantly. In the medium containing 3 g l(-1) acetic acid, the
      optimal xylose concentration for BC production was 20 g l(-1). In the medium
      containing 20 g l(-1) xylose, the xylose utilization and BC production by G.
      xylinus were stimulated by acetic acid within certain concentration. The highest
      BC yield (1.35 +/- 0.06 g l(-1)) was obtained in the medium containing 20 g l(-1)
      xylose and 3 g l(-1) acetic acid after 14 days. This value was 6.17-fold higher
      than the yield (0.21 +/- 0.01 g l(-1)) in the medium only containing 20 g l(-1)
      xylose. The results analyzed by FE-SEM, FTIR, and XRD showed that acetic acid
      affected little on the microscopic morphology and physicochemical characteristics
      of BC. Base on the phenomenon observed, lignocellulosic acid hydrolysates (xylose
      and acetic acid are main carbon sources present in it) could be considered as one
      potential substrate for BC production. 

PMID- 24891731
TI  - Technicalities and Glitches of Terminal Restriction Fragment Length Polymorphism
      (T-RFLP).
AB  - Terminal restriction fragment length polymorphism (T-RFLP) is a rapid, robust,
      inexpensive and simple tool for microbial community profiling. Methods used for
      DNA extraction, PCR amplification and digestion of amplified products have a
      considerable impact on the results of T-RFLP. Pitfalls of the method skew the
      similarity analysis and compromise its high throughput ability. Despite a high
      throughput method of data generation, data analysis is still in its infancy and
      needs more attention. Current article highlights the limitations of the methods
      used for data generation and analysis. It also provides an overview of the recent
      methodological developments in T-RFLP which will assist the readers in obtaining
      real and authentic profiles of the microbial communities under consideration
      while eluding the inherent biases and technical difficulties. 

PMID- 24891734
TI  - Gene Expressing Difference in Sclerotial Formation of Morchella conica.
AB  - The difference of gene expression between sclerotia-producing and non-sclerotia
      producing single spore isolates from Morchella conica were preliminary analyzed
      by mRNA differential display reverse transcription-polymerase chain reaction (RT
      PCR) technique and 67 differential gene fragments were obtained. Fifty-eight of
      their second PCR products were cloned and sequenced. Thirteen special
      differential gene fragments related to sclerotial formation were validated by
      semi-quantitative RT-PCR. Some gene fragments had certain homologies with
      lipoprotein, cyclin-dependent kinase C-3, glycerophosphoryl diester
      phosphodiesterase, Rho GDP-dissociation inhibitor, gamma-aminobutyrate permease,
      OmpA family protein, Transcript antisense to ribosomal RNA protein, sodium
      calcium exchange protein and keratin-associated proteins 5, 6. In addition, the
      putative protein of some DNA fragments had higher similarity with hypothetical
      protein-coding gene in NCBI database, as well as some were only putative gene
      fragments. All these fragments were speculated to be the functional gene
      associated with sclerotial formation in morel. 

PMID- 24891735
TI  - Cloning, expression and characterization of a lipase encoding gene from human
      oral metagenome.
AB  - The human oral metagenomic DNA cloned into plasmid pUC19 was used to construct a
      DNA library in Escherichia coli. Functional screening of 40,000 metagenomic
      clones led to identification of a clone LIP2 that exhibited halo on tributyrin
      agar plate. Sequence analysis of LIP2 insert DNA revealed a 939 bp ORF (omlip1)
      which showed homology to lipase 1 of Acinetobacter junii SH205. The omlip1 ORF
      was cloned and expressed in E. coli BL21 (DE3) using pET expression system. The
      recombinant enzyme was purified to homogeneity and the biochemical properties
      were studied. The purified OMLip1 hydrolyzed p-nitrophenyl esters and
      triacylglycerol esters of medium and long chain fatty acids, indicating the
      enzyme is a true lipase. The purified protein exhibited a pH and temperature
      optima of 7 and 37  degrees C respectively. The lipase was found to be stable at
      pH range of 6-7 and at temperatures lower than 40  degrees C. Importantly, the
      enzyme activity was unaltered, by the presence or absence of many divalent
      cations. The metal ion insensitivity of OMLip1offers its potential use in
      industrial processes. 

PMID- 24891737
TI  - In Vitro Evaluation of Antagonism of Endophytic Colletotrichum gloeosporioides
      Against Potent Fungal Pathogens of Camellia sinensis.
AB  - An endophytic fungus isolated from Camellia sinensis, Assam, Northeastern India
      was identified as Colletotrichum gloeosporioides on the basis of morphological
      characteristics and rDNA ITS analysis. This endophytic fungus was evaluated for
      growth inhibition against tea pathogens Pestalotiopsis theae and Colletotrichum
      camelliae. One isolate of C. gloeosporioides showed strong antagonistic activity
      against Pestalotiopsis theae (64 %) and moderate activity against C. camelliae
      (37 %). Fifty percent cell-free culture filtrate from 5-day-old cultures showed
      highest antagonistic activity against both the pathogens although the inhibition
      percent was less as compared to dual culture. In the experiment of volatile
      compounds none of the isolates of C. gloeosporioides strains showed visible
      inhibition against P. theae and C. camelliae. The activity of extracellular
      hydrolytic enzymes chitinase and protease was also high in this culture fluid and
      measured 10 and 4.3 IU/MUl, respectively. 

PMID- 24891736
TI  - Comparative Genomic Analysis of Two-Component Signal Transduction Systems in
      Probiotic Lactobacillus casei.
AB  - Lactobacillus casei has traditionally been recognized as a probiotic, thus
      needing to survive the industrial production processes and transit through the
      gastrointestinal tract before providing benefit to human health. The two
      component signal transduction system (TCS) plays important roles in sensing and
      reacting to environmental changes, which consists of a histidine kinase (HK) and
      a response regulator (RR). In this study we identified HKs and RRs of six
      sequenced L. casei strains. Ortholog analysis revealed 15 TCS clusters (HK-RR
      pairs), one orphan HKs and three orphan RRs, of which 12 TCS clusters were common
      to all six strains, three were absent in one strain. Further classification of
      the predicted HKs and RRs revealed interesting aspects of their putative
      functions. Some TCS clusters are involved with the response under the stress of
      the bile salts, acid, or oxidative, which contribute to survive the difficult
      journey through the human gastrointestinal tract. Computational predictions of 15
      TCSs were verified by PCR experiments. This genomic level study of TCSs should
      provide valuable insights into the conservation and divergence of TCS proteins in
      the L. casei strains. 

PMID- 24891738
TI  - Isolation and Characterization of the PKAr Gene From a Plant Pathogen, Curvularia
      lunata.
AB  - By using EST database from a full-length cDNA library of Curvularia lunata, we
      have isolated a 2.9 kb cDNA, termed PKAr. An ORF of 1,383 bp encoding a
      polypeptide of 460 amino acids with molecular weight 50.1 kDa, (GeneBank Acc. No.
      KF675744) was cloned. The deduced amino acid sequence of the PKAr shows 90 and 88
      % identity with cAMP-dependent protein kinase A regulatory subunit from
      Alternaria alternate and Pyrenophora tritici-repentis Pt-1C-BFP, respectively.
      Database analysis revealed that the deduced amino acid sequence of PKAr shares
      considerable similarity with that of PKA regulatory subunits in other organisms,
      particularly in the conserved regions. No introns were identified within the
      1,383 bp of ORF compared with PKAr genomic DNA sequence. Southern blot indicated
      that PKAr existed as a single copy per genome. The mRNA expression level of PKAr
      in different development stages were demonstrated using real-time quantitative
      PCR. The results showed that the level of PKAr expression was highest in
      vegetative growth mycelium, which indicated it might play an important role in
      the vegetative growth of C. lunata. These results provided a fundamental
      supporting research on the function of PKAr in plant pathogen, C. lunata. 

PMID- 24891739
TI  - Characterization and Fungal Inhibition Activity of Siderophore from Wheat
      Rhizosphere Associated Acinetobacter calcoaceticus Strain HIRFA32.
AB  - Acinetobacter calcoaceticus HIRFA32 from wheat rhizosphere produced catecholate
      type of siderophore with optimum siderophore (ca. 92 % siderophore units) in
      succinic acid medium without FeSO4 at 28  degrees C and 24 h of incubation. HPLC
      purified siderophore appeared as pale yellow crystals with molecular weight
      [M(+1)] m/z 347.18 estimated by LCMS. The structure elucidated by (1)H NMR, (13)C
      NMR, HMQC, HMBC, NOESY and decoupling studies, revealed that siderophore composed
      of 2,3-dihydroxybenzoic acid with hydroxyhistamine and threonine as amino acid
      subunits. In vitro study demonstrated siderophore mediated mycelium growth
      inhibition (ca. 46.87 +/- 0.5 %) of Fusarium oxysporum. This study accounts to
      first report on biosynthesis of acinetobactin-like siderophore by the
      rhizospheric strain of A. calcoaceticus and its significance in inhibition of F.
      oxysporum. 

PMID- 24891740
TI  - Efficacy of cryptdin-2 as an adjunct to antibiotics from various generations
      against salmonella.
AB  - Emerging drug resistance in Salmonella coupled with the recent poor success rate
      of antibiotic discovery programs of the pharmaceutical industry is a cause for
      significant concern. It has forced the scientific community to look for
      alternative new classes of antimicrobial compounds. In this context, combinations
      of antimicrobial peptides (AMPs) and conventional antibiotics have gained
      interest owing to their versatile applications. The present study was therefore
      planned to evaluate the synergistic effects, if any, of cryptdin-2, a mouse
      Paneth cell alpha-defensin, in combination with four different antibiotics i.e.
      ciprofloxacin, ceftriaxone, cefotaxime and chloramphenicol, which are
      conventionally used against Salmonella. Minimum bactericidal concentrations of
      the selected antimicrobial agents were determined by micro and macro broth
      dilution assays. In-vitro synergy between the agents was evaluated by fractional
      bactericidal concentration index (checkerboard test) and time-kill assay.
      Cryptdin-2-ciprofloxacin, cryptdin-2-ceftriaxone and cryptdin-2-cefotaxime
      combinations were found synergistic as evident by in vitro assays. This synergism
      provides an additional therapeutic choice by allowing the use of conventional
      antibiotics in conjunction with AMPs against MDR Salmonella. 

PMID- 24891741
TI  - Production and Characterization of Protein Encapsulated Silver Nanoparticles by
      Marine Isolate Streptomyces parvulus SSNP11.
AB  - Production of protein encapsulated silver nanoparticles (AgNPs) assisted by
      marine actinomycetes strain has been investigated. The selective isolate was
      identified as Streptomyces parvulus SSNP11 based on chemotaxonomic and 16S rRNA
      analysis. Maximum AgNPs production was observed within 24 h incubation time. The
      produced AgNPs are spherical in shape with monodispersive and crystalline in
      nature. The particle size distribution ranges from 1.66 to 11.68 nm with a mean
      size of 2.1 nm. The biosynthesized AgNPs revealed stretching vibrations of
      primary and secondary amines along with C-H and C-N, suggesting that
      metabolically produced proteins are involved in size regulation of reduced AgNPs.
      These particles possess an average negative zeta potential value of 81.5 mV with
      an electrophoretic mobility of 0.000628 cm(2)/Vs. The biosynthesized
      nanoparticles revealed antimicrobial property against gram negative as well as
      gram positive bacterial strains. 

PMID- 24891742
TI  - Degradation of Di- Through Hepta-Chlorobiphenyls in Clophen Oil Using
      Microorganisms Isolated from Long Term PCBs Contaminated Soil.
AB  - Present work describes microbial degradation of selected polychlorinated
      biphenyls (PCBs) congeners in Clophen oil which is used as transformer oil and
      contains high concentration of PCBs. Indigenous PCBs degrading bacteria were
      isolated from Clophen oil contaminated soil using enrichment culture technique. A
      15 days study was carried out to assess the biodegradation potential of two
      bacterial cultures and their consortium for Clophen oil with a final PCBs
      concentration of 100 mg kg(-1). The degradation capability of the individual
      bacterium and the consortium towards the varying range of PCBs congeners (di-
      through hepta-chlorobiphenyls) was determined using GCMS. Also, dehydrogenase
      enzyme was estimated to assess the microbial activity. Maximum degradation was
      observed in treatment containing consortium that resulted in up to 97 %
      degradation of PCB-44 which is a tetra chlorinated biphenyl whereas, hexa
      chlorinated biphenyl congener (PCB-153) was degraded up to 90 % by the
      consortium. This indicates that the degradation capability of microbial
      consortium was significantly higher than that of individual cultures.
      Furthermore, the results suggest that for degradation of lower as well as higher
      chlorinated PCB congeners; a microbial consortium is required rather than
      individual cultures. 

PMID- 24891743
TI  - Morphological and Molecular Differentiation of Sporidiobolus johnsonii ATCC 20490
      and Its Coenzyme Q10 Overproducing Mutant Strain UF16.
AB  - Coenzyme Q10 (CoQ10) is an industrially important molecule having nutraceutical
      and cosmeceutical applications. CoQ10 is mainly produced by microbial
      fermentation and the process demands the use of strains with high productivity
      and yields of CoQ10. During strain improvement program consisting of sequential
      induced mutagenesis, rational selection and screening process, a mutant strain
      UF16 was generated from Sporidiobolus johnsonii ATCC 20490 with 2.3-fold
      improvements in CoQ10 content. EMS and UV rays were used as mutagenic agents for
      generating UF16 and it was rationally selected based on atorvastatin resistance
      as well as survival at free radicals exposure. We investigated the genotypic and
      phenotypic changes in UF16 in order to differentiate it from wild type strain.
      Morphologically it was distinct due to reduced pigmentation of colony, reduced
      cell size and significant reduction in mycelial growth forms with abundance of
      yeast forms. At molecular level, UF16 was differentiated based on PCR
      fingerprinting method of RAPD as well as large and small-subunit rRNA gene
      sequences. Rapid molecular technique of RAPD analysis using six primers showed 34
      % polymorphic fragments with mean genetic distance of 0.235. The partial
      sequences of rRNA-gene revealed few mutation sites on nucleotide base pairs.
      However, the mutations detected on rRNA gene of UF16 were less than 1 % of total
      base pairs and its sequence showed 99 % homology with the wild type strain. These
      mutations in UF16 could not be linked to phenotypic or genotypic changes on CoQ10
      biosynthetic pathway that resulted in improved yield. Hence, investigating the
      mutations responsible for deregulation of CoQ10 pathway is essential to
      understand the cause of overproduction in UF16. Phylogenetic analysis based on
      RAPD bands and rRNA gene sequences coupled with morphological variations,
      exhibited the novelty of mutant UF16 having potential for improved CoQ10
      production. 

PMID- 24891744
TI  - Electron Microscopy and X-ray Analysis of Cr-Containing Precipitates Synthesized
      by Newly Isolated Actinobacterium, Flexivirga alba ST13(T.).
AB  - Chromium(Cr) precipitate synthesized by Cr(VI)-reducing bacterium Flexivirga alba
      ST13(T) was examined using transmission electron microscopy (TEM) and the energy
      dispersive X-ray (EDX). The strain showed altered-morphology after exposing to
      Cr(VI) in minimal medium. The resultant precipitate included bacterial pellet and
      needle-like structure which was similar to the structure made from Cr(OH)3
      precipitate. Cr was observed in bacterial cells using TEM-EDX. Bacteria with high
      electron density showed the precipitation of Ca in addition to Cr. The isolated
      strain would be useful to precipitate Cr from Cr(VI)-containing environment. 

PMID- 24891745
TI  - Comparison of antimicrobial activity of essential oils, plant extracts and
      methylparaben in cosmetic emulsions: 2 months study.
AB  - The aim of the study was to compare the preservative effectiveness of plant
      extracts (Matricaria chamomilla, Aloe vera, Calendula officinalis) and essential
      oils (Lavandulla officinalis, Melaleuca alternifolia, Cinnamomum zeylanicum) with
      methylparaben in cosmetic emulsions against skin microflora during 2 months of
      application by volunteers. Cosmetic emulsions with extracts (2.5 %), essential
      oils (2.5 %), methylparaben (0.4 %) or placebo were tested by 40 volunteers
      during 2 months of treatment. In order to determine microbial purity of the
      emulsions, the samples were taken after 0, 2, 4, 6 and 8 weeks of application.
      Throughout the trial period it was revealed that only cinnamon oil completely
      inhibited the growth of bacteria, yeast and mould, as compared to all other
      essential oils, plant extracts and methylparaben in the tested emulsions. This
      result shows that cinnamon oil could successfully replace the use of
      methylparaben in cosmetics, at the same time ensuring microbiological purity of a
      cosmetic product under its in-use and storage conditions. 

PMID- 24891746
TI  - Comparative study of antibiofilm activity of copper oxide and iron oxide
      nanoparticles against multidrug resistant biofilm forming uropathogens.
AB  - The effectiveness of the metal oxide nanoparticles viz. CuO and Fe2O3 as
      antibacterial agents against multidrug resistant biofilm forming bacteria was
      evaluated. CuO nanoparticles were also experimented for antibiofilm and time kill
      assay. The CuO displayed maximum antibacterial activity with zone of inhibition
      of (22 +/- 1) mm against methicillin resistant Staphylococcus aureus (MRSA)
      followed by Escherichia coli (18 +/- 1) mm. The Fe2O3 showed the zone of
      inhibition against MRSA of (14 +/- 1) mm followed by E. coli (12 +/- 1) mm. CuO
      proved to be more toxic than Fe2O3 nanoparticles showing significantly high
      antibacterial activity and found to possess dose dependent antibiofilm
      properties. 

PMID- 24891747
TI  - A Nondestructive Evaluation Method: Measuring the Fixed Strength of Spot-Welded
      Joint Points by Surface Electrical Resistivity.
AB  - Destructive tests are generally applied to evaluate the fixed strength of spot
      welding nuggets of zinc-plated steel (which is a widely used primary structural
      material for automobiles). These destructive tests, however, are expensive and
      time-consuming. This paper proposes a nondestructive method for evaluating the
      fixed strength of the welded joints using surface electrical resistance. A direct
      current nugget-tester and probes have been developed by the authors for this
      purpose. The proposed nondestructive method uses the relative decrease in surface
      electrical resistance, alpha. The proposed method also considers the effect of
      the corona bond. The nugget diameter is estimated by two factors: RQuota, which
      is calculated from variation of resistance, and a constant that represents the
      area of the corona bond. Since the maximum tensile strength is correlated with
      the nugget diameter, it can be inferred from the estimated nugget diameter. When
      appropriate measuring conditions for the surface electrical resistance are
      chosen, the proposed method can effectively evaluate the fixed strength of the
      spot-welded joints even if the steel sheet is zinc-plated.

PMID- 24891748
TI  - Calculating the Optimum Angle of Filament-Wound Pipes in Natural Gas Transmission
      Pipelines Using Approximation Methods.
AB  - Given the increasing use of composite materials in various industries, oil and
      gas industry also requires that more attention should be paid to these materials.
      Furthermore, due to variation in choice of materials, the materials needed for
      the mechanical strength, resistance in critical situations such as fire, costs
      and other priorities of the analysis carried out on them and the most optimal for
      achieving certain goals, are introduced. In this study, we will try to introduce
      appropriate choice for use in the natural gas transmission composite pipelines.
      Following a 4-layered filament-wound (FW) composite pipe will consider an offer
      our analyses under internal pressure. The analyses' results will be calculated
      for different combinations of angles 15 deg, 30 deg, 45 deg, 55 deg, 60 deg, 75
      deg, and 80 deg. Finally, we will compare the calculated values and the optimal
      angle will be gained by using the Approximation methods. It is explained that
      this layering is as the symmetrical.

PMID- 24891749
TI  - Long-Term Stability of Residual Stress Improvement by Water Jet Peening
      Considering Working Processes.
AB  - To prevent primary water stress corrosion cracking (PWSCC), water jet peening
      (WJP) has been used on the welds of Ni-based alloys in pressurized water reactors
      (PWRs). Before WJP, the welds are machined and buffed in order to conduct a
      penetrant test (PT) to verify the weld qualities to access, and microstructure
      evolution takes place in the target area due to the severe plastic deformation.
      The compressive residual stresses induced by WJP might be unstable under elevated
      temperatures because of the high dislocation density in the compressive stress
      layer. Therefore, the stability of the compressive residual stresses caused by
      WJP was investigated during long-term operation by considering the microstructure
      evolution due to the working processes. The following conclusions were made: The
      compressive residual stresses were slightly relaxed in the surface layers of the
      thermally aged specimens. There were no differences in the magnitude of the
      relaxation based on temperature or time. The compressive residual stresses
      induced by WJP were confirmed to remain stable under elevated temperatures. The
      stress relaxation at the surface followed the Johnson-Mehl equation, which states
      that stress relaxation can occur due to the recovery of severe plastic strain,
      since the estimated activation energy agrees very well with the self-diffusion
      energy for Ni. By utilizing the additivity rule, it was indicated that stress
      relaxation due to recovery is completed during the startup process. It was
      proposed that the long-term stability of WJP under elevated temperatures must be
      assessed based on compressive stresses with respect to the yield stress. Thermal
      elastic-plastic creep analysis was performed to predict the effect of creep
      strain. After 100 yr of simulated continuous operation at 80% capacity, there was
      little change in the WJP compressive stresses under an actual operating
      temperature of 623 K. Therefore, the long-term stability of WJP during actual
      operation was analytically predicted.

PMID- 24891750
TI  - Sensitivity Analysis of Fitness-for-Service Assessment Based on Reliability for
      Cylindrical Pressure Vessels With Local Metal Loss.
AB  - Concern about fitness-for-service (FFS) assessments using stochastic analyses for
      aged pressure equipment with local metal loss has been growing. When a decision
      must be made regarding whether to run or repair equipment with local metal loss,
      a structural integrity assessment based on reliability helps. In analyses of
      failure probability, it is important to identify which variables strongly affect
      the structural integrity. The stochastic properties of influential parameters
      must be clarified, but few data have been published regarding the quantitative
      analysis of the sensitivity of the parameters in FFS assessments of components
      with local metal loss. Here, we investigated the effects of parameters on the
      plastic collapse of a damaged cylindrical pressure vessel with local metal loss,
      in an evaluation of parameter sensitivity. We also analyzed sensitivity indices
      for the component with several shapes of local metal loss. We found that the
      corrosion rate has a major influence on the probability of failure. We propose a
      practical stochastic analysis procedure for components with local metal loss. In
      this procedure, the parameter that has consistently low sensitivity to the limit
      state is used as a constant value.

PMID- 24891751
TI  - A Method Using Optical Contactless Displacement Sensors to Measure Vibration
      Stress of Small-Bore Piping.
AB  - In nuclear power plants, vibration stress of piping is frequently evaluated to
      prevent fatigue failure. A simple and fast measurement method is attractive to
      evaluate many piping systems efficiently. In this study, a method to measure the
      vibration stress using optical contactless displacement sensors was proposed, the
      prototype instrument was developed, and the instrument practicality for the
      method was verified. In the proposed method, light emitting diodes (LEDs) were
      used as measurement sensors and the vibration stress was estimated by measuring
      the deformation geometry of the piping caused by oscillation, which was measured
      as the piping curvature radius. The method provided fast and simple vibration
      estimates for small-bore piping. Its verification and practicality were confirmed
      by vibration tests using a test pipe and mock-up piping. The stress measured by
      both the proposed method and an accurate conventional method using strain gauges
      were in agreement, and it was concluded that the proposed method could be used
      for actual plant piping systems.

PMID- 24891752
TI  - The Effect of Microstructure, Thickness Variation, and Crack on the Natural
      Frequency of Solar Silicon Wafers.
AB  - Vibration is one of the most common loading modes during handling and transport
      of solar silicon wafers and has a great influence on the breakage rate. In order
      to control the breakage rate during handling and facilitate the optimization of
      the processing steps, it is important to understand the factors which influence
      the natural frequency of thin silicon wafers. In this study, we applied nonlinear
      finite element method to investigate the correlation of natural frequency of thin
      solar silicon wafer with material microstructures (grain size and grain
      orientation), thickness variation and crack geometry (position and size). It has
      been found that the natural frequency for anisotropic single crystal silicon
      wafer is a strong function of material orientation. Less than 10% thickness
      variation will have a negligible effect on natural frequency. It is also found
      out that cracks smaller than 20 mm have no dominant effect on the first five
      natural frequency modes anywhere in the silicon wafer.

PMID- 24891753
TI  - Surface-Bound Ruthenium Diimine Organometallic Complexes: Excited-State
      Properties.
AB  - Ruthenium complexes of the general formula [Ru(CO)(H)(L2)(L'2)][PF6] (L2 = trans
      2PPh3, L' = eta2-4,4'-dicarboxybipyridine (1); L2 =trans-2Ph2PCH2CH2COOH, L'2 =
      bipyridine (2); L2 = Ph2PCHCHPPh2, L' = eta2-5-amino-1,10-phenanthroline (3); L2
      = trans-2PPh3, L'2 = eta2-4-carboxaldehyde-4'-methylbipyridine (4)) have been
      shown to have longer emission lifetimes and higher quantum yields in solution
      compared with more symmetrical molecules such as [Ru(bpy)3][Cl]2. Compound 4 is
      obtained as a mixture with the corresponding acetal, 4'. These less symmetrical
      complexes have been covalently immobilized on the surface of silica polyamine
      composites, and their photophysical properties have been studied. The surface
      bound complexes have been characterized by solid-state CPMAS 13C, 31P, and 29Si
      NMR, UV-vis, and FT-IR spectroscopies. Excited-state lifetime studies revealed
      that, in general, the lifetimes of the immobilized complexes are 1.4 to 8 times
      longer than in solution and are dependent on particle size (300-500 MUm versus 10
      20 nm average diameter silica gels), polymer structure (linear poly(allylamine)
      versus branched poly(ethylenimine)), and the type of surface tether. One
      exception to this trend is the previously reported complex [Ru(bpy)2(5-amino-1,10
      phenanthroline)][PF6]2 (5), where only a slight increase in lifetime is observed.
      Only minor changes in emission wavelength are observed for all the complexes.
      This opens up the possibility for enhanced heterogeneous electron transfer in
      photocatalytic reactions.

PMID- 24891754
TI  - Ring-Opening Polymerization of rac-Lactide with Aluminum Chiral Anilido
      Oxazolinate Complexes.
AB  - A series of dimethylaluminum complexes (L1a-i )AlMe2 (2a-i, where HL1a-i = 2-(2'
      ArNH)phenyl-4-R1-oxazoline) bearing chiral, bidentate anilido-oxazolinate ligands
      have been prepared and characterized. Six of the complexes, in the presence of an
      alcohol cocatalyst, are shown to be active initiators for the stereoselective
      ring-opening polymerization of rac-lactide in toluene solution and under bulk
      conditions, yielding polylactides with a range of tacticity from slightly
      isotactic to moderately heterotactic. The reactivity and selectivity of these
      catalysts are discussed on the basis of the effect of their substituents.

PMID- 24891756
TI  - Validation and Analysis of Numerical Results for a Two-Pass Trapezoidal Channel
      With Different Cooling Configurations of Trailing Edge.
AB  - High inlet temperatures in a gas turbine lead to an increase in the thermal
      efficiency of the gas turbine. This results in the requirement of cooling of gas
      turbine blades/vanes. Internal cooling of the gas turbine blade/vanes with the
      help of two-pass channels is one of the effective methods to reduce the metal
      temperatures. In particular, the trailing edge of a turbine vane is a critical
      area, where effective cooling is required. The trailing edge can be modeled as a
      trapezoidal channel. This paper describes the numerical validation of the heat
      transfer and pressure drop in a trapezoidal channel with and without orthogonal
      ribs at the bottom surface. A new concept of ribbed trailing edge has been
      introduced in this paper which presents a numerical study of several trailing
      edge cooling configurations based on the placement of ribs at different walls.
      The baseline geometries are two-pass trapezoidal channels with and without
      orthogonal ribs at the bottom surface of the channel. Ribs induce secondary flow
      which results in enhancement of heat transfer; therefore, for enhancement of heat
      transfer at the trailing edge, ribs are placed at the trailing edge surface in
      three different configurations: first without ribs at the bottom surface, then
      ribs at the trailing edge surface in-line with the ribs at the bottom surface,
      and finally staggered ribs. Heat transfer and pressure drop is calculated at
      Reynolds number equal to 9400 for all configurations. Different turbulent models
      are used for the validation of the numerical results. For the smooth channel low
      Re k-E model, realizable k-E model, the RNG k-omega model, low-Re k-omega model,
      and SST k-omega models are compared, whereas for ribbed channel, low-Re k-E model
      and SST k-omega models are compared. The results show that the low-Re k-E model,
      which predicts the heat transfer in outlet pass of the smooth channels with
      difference of +7%, underpredicts the heat transfer by -17% in case of ribbed
      channel compared to experimental data. Using the same turbulence model shows that
      the height of ribs used in the study is not suitable for inducing secondary flow.
      Also, the orthogonal rib does not strengthen the secondary flow rotational
      momentum. The comparison between the new designs for trailing edge shows that if
      pressure drop is acceptable, staggered arrangement is suitable for the outlet
      pass heat transfer. For the trailing edge wall, the thermal performance for the
      ribbed trailing edge only was found about 8% better than other configurations.

PMID- 24891757
TI  - Stability Improvement of High-Pressure-Ratio Turbocharger Centrifugal Compressor
      by Asymmetric Flow Control-Part I: Non-Axisymmetrical Flow in Centrifugal
      Compressor.
AB  - This is Part I of a two-part paper documenting the development of a novel
      asymmetric flow control method to improve the stability of a high-pressure-ratio
      turbocharger centrifugal compressor. Part I focuses on the nonaxisymmetrical flow
      in a centrifugal compressor induced by the nonaxisymmetrical geometry of the
      volute while Part II describes the development of an asymmetric flow control
      method to avoid the stall on the basis of the characteristic of nonaxisymmetrical
      flow. To understand the asymmetries, experimental measurements and corresponding
      numerical simulation were carried out. The static pressure was measured by probes
      at different circumferential and stream-wise positions to gain insights about the
      asymmetries. The experimental results show that there is an evident
      nonaxisymmetrical flow pattern throughout the compressor due to the asymmetric
      geometry of the overhung volute. The static pressure field in the diffuser is
      distorted at approximately 90 deg in the rotational direction of the volute
      tongue throughout the diffuser. The magnitude of this distortion slightly varies
      with the rotational speed. The magnitude of the static pressure distortion in the
      impeller is a function of the rotational speed. There is a significant phase
      shift between the static pressure distributions at the leading edge of the
      splitter blades and the impeller outlet. The numerical steady state simulation
      neglects the aforementioned unsteady effects found in the experiments and cannot
      predict the phase shift, however, a detailed asymmetric flow field structure is
      obviously obtained.

PMID- 24891755
TI  - Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio: novel markers
      for diagnosis and prognosis in patients with idiopathic sudden sensorineural
      hearing loss.
AB  - BACKGROUND: We aim to provide useful evidence about the association of neutrophil
      to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with idiopathic
      sudden sensorineural hearing loss (ISSNHL) and its possibility of emerging as a
      cheap, reliable, and independent prognostic marker of ISSNHL. METHODS: 348
      patients diagnosed with ISSNHL were included in our retrospective data analysis.
      Blood samples and the hearing assessments of the patients were carried out. Then,
      the patients were divided into 2 groups as "recovered" and "unrecovered"
      according to their response to the treatment. RESULTS: Both mean NLR and PLR
      values of the ISSNHL patients were significantly higher than the control group
      (both P < 0.001). The NLR value was 5.98 +/- 4.22 in the unrecovered group and
      3.50 +/- 3.38 in the recovered group (P < 0.001). After adjustment in a binary
      logistic regression model, only NLR value was associated with the recovery of
      ISSNHL (P = 0.001). DISCUSSION: We demonstrated for the first time that NLR and
      PLR values were significantly high in ISSNHL patients. Also the NLR level might
      be taken into account as a novel potential marker to predict the patients'
      prognosis in terms of recovery.

PMID- 24891758
TI  - Stability Improvement of High-Pressure-Ratio Turbocharger Centrifugal Compressor
      by Asymmetrical Flow Control-Part II: Nonaxisymmetrical Self-Recirculation Casing
      Treatment.
AB  - This is part II of a two-part paper involving the development of an asymmetrical
      flow control method to widen the operating range of a turbocharger centrifugal
      compressor with high-pressure ratio. A nonaxisymmetrical self-recirculation
      casing treatment (SRCT) as an instance of asymmetrical flow control method is
      presented. Experimental and numerical methods were used to investigate the impact
      of nonaxisymmetrical SRCT on the surge point of the centrifugal compressor.
      First, the influence of the geometry of a symmetric SRCT on the compressor
      performance was studied by means of numerical simulation. The key parameter of
      the SRCT was found to be the distance from the main blade leading edge to the
      rear groove (Sr). Next, several arrangements of a nonaxisymmetrical SRCT were
      designed, based on flow analysis presented in part I. Then, a series of
      experiments were carried out to analyze the influence of nonaxisymmetrical SRCT
      on the compressor performance. Results show that the nonaxisymmetrical SRCT has a
      certain influence on the performance and has a larger potential for stability
      improvement than the traditional symmetric SRCT. For the investigated SRCT, the
      surge flow rate of the compressor with the nonaxisymmetrical SRCTs is about 10%
      lower than that of the compressor with symmetric SRCT. The largest surge margin
      (smallest surge flow rate) can be obtained when the phase of the largest Sr is
      coincident with the phase of the minimum static pressure in the vicinity of the
      leading edge of the splitter blades.

PMID- 24891759
TI  - Performance Improvement of a Return Channel in a Multistage Centrifugal
      Compressor Using Multiobjective Optimization.
AB  - The effect of the design parameters of a return channel on the performance of a
      multistage centrifugal compressor was numerically investigated, and the shape of
      the return channel was optimized using a multiobjective optimization method based
      on a genetic algorithm to improve the performance of the centrifugal compressor.
      The results of sensitivity analysis using Latin hypercube sampling suggested that
      the inlet-to-outlet area ratio of the return vane affected the total pressure
      loss in the return channel, and that the inlet-to-outlet radius ratio of the
      return vane affected the outlet flow angle from the return vane. Moreover, this
      analysis suggested that the number of return vanes affected both the loss and the
      flow angle at the outlet. As a result of optimization, the number of return vane
      was increased from 14 to 22 and the area ratio was decreased from 0.71 to 0.66.
      The radius ratio was also decreased from 2.1 to 2.0. Performance tests on a
      centrifugal compressor with two return channels (the original design and
      optimized design) were carried out using two-stage test apparatus. The measured
      flow distribution exhibited a swirl flow in the center region and a reversed
      swirl flow near the hub and shroud sides. The exit flow of the optimized design
      was more uniform than that of the original design. For the optimized design, the
      overall two-stage efficiency and pressure coefficient were increased by 0.7% and
      1.5%, respectively. Moreover, the second-stage efficiency and pressure
      coefficient were respectively increased by 1.0% and 3.2%. It is considered that
      the increase in the second-stage efficiency was caused by the increased
      uniformity of the flow, and the rise in the pressure coefficient was caused by a
      decrease in the residual swirl flow. It was thus concluded from the numerical and
      experimental results that the optimized return channel improved the performance
      of the multistage centrifugal compressor.

PMID- 24891761
TI  - The pathology of orthopedic implant failure is mediated by innate immune system
      cytokines.
AB  - All of the over 1 million total joint replacements implanted in the US each year
      are expected to eventually fail after 15-25 years of use, due to slow progressive
      subtle inflammation at the bone implant interface. This inflammatory disease
      state is caused by implant debris acting, primarily, on innate immune cells, that
      is, macrophages. This slow progressive pathological bone loss or "aseptic
      loosening" is a potentially life-threatening condition due to the serious
      complications in older people (>75 yrs) of total joint replacement revision
      surgery. In some people implant debris (particles and ions from metals) can
      influence the adaptive immune system as well, giving rise to the concept of metal
      sensitivity. However, a consensus of studies agrees that the dominant form of
      this response is due to innate reactivity by macrophages to implant debris where
      both danger (DAMP) and pathogen (PAMP) signalling elicit cytokine-based
      inflammatory responses. This paper discusses implant debris induced release of
      the cytokines and chemokines due to activation of the innate (and the adaptive)
      immune system and the subsequent formation of osteolysis. Different mechanisms of
      implant-debris reactivity related to the innate immune system are detailed, for
      example, danger signalling (e.g., IL-1beta, IL-18, IL-33, etc.), toll-like
      receptor activation (e.g., IL-6, TNF-alpha, etc.), apoptosis (e.g., caspases 3
      9), bone catabolism (e.g., TRAP5b), and hypoxia responses (Hif1-alpha). Cytokine
      based clinical and basic science studies are in progress to provide diagnosis and
      therapeutic intervention strategies.

PMID- 24891760
TI  - Two faces of TGF-beta1 in breast cancer.
AB  - Breast cancer (BC) is potentially life-threatening malignancy that still causes
      high mortality among women. Scientific research in this field is focused on
      deeper understanding of pathogenesis and progressing of BC, in order to develop
      relevant diagnosis and improve therapeutic treatment. Multifunctional cytokine
      TGF- beta 1 is one of many factors that have a direct influence on BC
      pathophysiology. Expression of TGF- beta 1, induction of canonical and
      noncanonical signaling pathways, and mutations in genes encoding TGF- beta 1 and
      its receptors are correlated with oncogenic activity of this cytokine. In early
      stages of BC this cytokine inhibits epithelial cell cycle progression and
      promotes apoptosis, showing tumor suppressive effects. However, in late stages,
      TGF- beta 1 is linked with increased tumor progression, higher cell motility,
      cancer invasiveness, and metastasis. It is also involved in cancer
      microenvironment modification and promotion of epithelial to mesenchymal
      transition (EMT). This review summarizes the current knowledge on the phenomenon
      called "TGF- beta 1 paradox", showing that better understanding of TGF- beta 1
      functions can be a step towards development of new therapeutic approaches.
      According to current knowledge several drugs against TGF- beta 1 have been
      developed and are either in nonclinical or in early stages of clinical
      investigation. 

PMID- 24891762
TI  - Blockade of ICAM-1 improves the outcome of polymicrobial sepsis via modulating
      neutrophil migration and reversing immunosuppression.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is a key adhesion molecule mediating
      neutrophil migration and infiltration during sepsis. But its role in the outcome
      of sepsis remains contradictory. The current study was performed to investigate
      the role of anti-ICAM-1 antibody in the outcome of polymicrobial sepsis and
      sepsis-induced immune disturbance. Effect of anti-ICAM-1 antibody on outcome of
      sepsis induced by cecal ligation and puncture (CLP) was evaluated by the survival
      analysis, bacterial clearance, and lung injury. Its influence on neutrophil
      migration and infiltration, as well as lymphocyte status, in thymus and spleen
      was also investigated. The results demonstrated that ICAM-1 mRNA was upregulated
      in lung, thymus, and spleen of CLP mice. Anti-ICAM-1 antibody improved survival
      and bacterial clearance in CLP mice and attenuated lung injury. Migration of
      neutrophils to peritoneal cavity was enhanced while their infiltration into lung,
      thymus, and spleen was hampered by ICAM-1 blockade. Anti-ICAM-1 antibody also
      prevented sepsis-induced apoptosis in thymus and spleen. Positive costimulatory
      molecules including CD28, CD80, and CD86 were upregulated, while negative
      costimulatory molecules including PD-1 and PD-L1 were downregulated following
      anti-ICAM-1 antibody administration. In conclusion, ICAM-1 blockade may improve
      outcome of sepsis. The rationale may include the modulated neutrophil migration
      and the reversed immunosuppression. 

PMID- 24891763
TI  - Adipokines NUCB2/nesfatin-1 and visfatin as novel inflammatory factors in chronic
      obstructive pulmonary disease.
AB  - COPD (chronic obstructive pulmonary disease) is a common lung disease
      characterized by airflow limitation and systemic inflammation. Recently, adipose
      tissue mediated inflammation has gathered increasing interest in the pathogenesis
      of the disease. In this study, we investigated the role of novel adipocytokines
      nesfatin-1 and visfatin in COPD by measuring if they are associated with the
      inflammatory activity, lung function, or symptoms. Plasma levels of
      NUCB2/nesfatin-1 and visfatin were measured together with IL-6, IL-8, TNF- alpha
      , and MMP-9, lung function, exhaled nitric oxide, and symptoms in 43 male
      patients with emphysematous COPD. The measurements were repeated in a subgroup of
      the patients after four weeks' treatment with inhaled fluticasone. Both visfatin
      and NUCB2/nesfatin-1 correlated positively with plasma levels of IL-6 (r = 0.341,
      P = 0.027 and rho = 0.401, P = 0.008, resp.) and TNF- alpha (r = 0.305, P = 0.052
      and rho = 0.329, P = 0.033, resp.) and NUCB2/nesfatin-1 also with IL-8 (rho =
      0.321, P = 0.036) in patients with COPD. Further, the plasma levels of visfatin
      correlated negatively with pulmonary diffusing capacity (r = -0.369, P = 0.016).
      Neither of the adipokines was affected by fluticasone treatment and they were not
      related to steroid-responsiveness. The present results introduce adipocytokines
      NUCB2/nesfatin-1 and visfatin as novel factors associated with systemic
      inflammation in COPD and suggest that visfatin may mediate impaired pulmonary
      diffusing capacity.

PMID- 24891764
TI  - Immune evasion strategies of pre-erythrocytic malaria parasites.
AB  - Malaria is a mosquito-borne infectious disease of humans. It begins with a bite
      from an infected female Anopheles mosquito and leads to the development of the
      pre-erythrocytic and blood stages. Blood-stage infection is the exclusive cause
      of clinical symptoms of malaria. In contrast, the pre-erythrocytic stage is
      clinically asymptomatic and could be an excellent target for preventive
      therapies. Although the robust host immune responses limit the development of the
      liver stage, malaria parasites have also evolved strategies to suppress host
      defenses at the pre-erythrocytic stage. This paper reviews the immune evasion
      strategies of malaria parasites at the pre-erythrocytic stage, which could
      provide us with potential targets to design prophylactic strategies against
      malaria. 

PMID- 24891765
TI  - Hesperidin inhibits inflammatory response induced by Aeromonas hydrophila
      infection and alters CD4+/CD8+ T cell ratio.
AB  - BACKGROUND: Aeromonas hydrophila is an opportunistic bacterial pathogen that is
      associated with a number of human diseases. Hesperidin (HES) has been reported to
      exert antioxidant and anti-inflammatory activities. OBJECTIVES: The aim of this
      study was to investigate the potential effect of HES treatment on inflammatory
      response induced by A. hydrophila infection in murine. METHODS: A. hydrophila
      infected mice were treated with HES at 250 mg/kg b.wt./week for 4 consecutive
      weeks. Phagocytosis, reactive oxygen species production, CD4(+)/CD8(+) T cell
      ratio, and CD14 expression on intestinal infiltrating monocytes were evaluated.
      The expression of E-selectin and intercellular adhesion molecule 1 on stimulated
      HUVECs and RAW macrophage was evaluated. RESULTS: Percentage of CD4(+) T cells in
      the intestinal tissues of infected treated mice was highly significantly
      increased; however, phagocytic index, ROS production, CD8(+) T cells percentage,
      and CD14 expression on monocytes were significantly reduced. On the other hand,
      HES significantly inhibited A-LPS- and A-ECP-induced E-selectin and ICAM-1
      expression on HUVECs and ICAM-1 expression on RAW macrophage. CONCLUSION: Present
      data indicated that HES has a potential role in the suppression of inflammatory
      response induced by A. hydrophila toxins through downmodulation of ROS production
      and CD14 and adhesion molecules expression, as well as increase of CD4(+)/CD8(+)
      cell ratio.

PMID- 24891766
TI  - Lycopene modulates THP1 and Caco2 cells inflammatory state through
      transcriptional and nontranscriptional processes.
AB  - We revisited the action of a carotenoid, the lycopene, on the expression of
      proinflammatory genes, reactive oxygen species (ROS) production, and
      metalloprotease (MMP9) activity. THP1 and Caco2 cell lines were used as in vitro
      models for the two main cell types found in intestine tissue, that is, monocytes
      and epithelial cells. Proinflammatory condition was induced using either phorbol
      ester acetate (PMA), lipopolysaccharide (LPS) or tumor necrosis factor (TNF). In
      THP1 cells, short term pretreatment (2 h) with a low concentration (2 MUM) of
      lycopene reinforce proinflammatory gene expression. The extent of the effect of
      lycopene is dependent on the proinflammtory stimulus (PMA, LPS or TNF) used.
      Lycopene enhanced MMP9 secretion via a c-AMP-dependent process, and reduced ROS
      production at higher concentrations than 2 MUM. Cell culture media, conditioned
      by PMA-treated monocytes and then transferred on CaCo-2 epithelial cells, induced
      a proinflammatory state in these cells. The extent of this inflammatory effect
      was reduced when cells has been pretreated (12 h) with lycopene. At low
      concentration (2 MUM or less), lycopene appeared to promote an inflammatory state
      not correlated with ROS modulation. At higher concentration (5 MUM-20 MUM), an
      anti-inflammatory effect takes place as a decrease of ROS production was
      detected. So, both concentration and time have to be considered in order to
      define the exact issue of the effect of carotenoids present in meals.

PMID- 24891767
TI  - CD226 rs763361 is associated with the susceptibility to type 1 diabetes and
      greater frequency of GAD65 autoantibody in a Brazilian cohort.
AB  - CD226 rs763361 variant increases susceptibility to type 1 diabetes (T1D) in
      Caucasians. There is no data about CD226 variants in the very heterogeneous
      Brazilian population bearing a wide degree of admixture. We investigated its
      association with T1D susceptibility, clinical phenotypes, and autoimmune
      manifestations (islet and extrapancreatic autoantibodies). Casuistry. 532 T1D
      patients and 594 controls in a case-control study. Initially, CD226 coding
      regions and boundaries were sequenced in a subset of 106 T1D patients and 102
      controls. In a second step, two CD226 variants, rs763361 (exon 7) and rs727088
      (3' UTR region), involved with CD226 regulation, were genotyped in the entire
      cohort. C-peptide and autoantibody levels were determined. No new polymorphic
      variant was found. The variants rs763361 and rs727088 were in strong linkage
      disequilibrium. The TT genotype of rs763361 was associated with TID risk (OR =
      1.503;  95%  CI = 1.135-1.991; P = 0.0044), mainly in females (P = 0.0012),
      greater frequency of anti-GAD autoantibody (31.9% * 24.5%; OR = 1.57; CI = 1.136
      2.194; P = 0.0081), and lower C-peptide levels when compared to those with TC +
      CC genotypes (0.41 +/- 0.30 ng/dL versus 0.70 +/- 0.53 ng/dL P = 0.0218).
      Conclusions. The rs763361 variant of CD226 gene (TT genotype) was associated with
      susceptibility to T1D and with the degree of aggressiveness of the disease in T1D
      patients from Brazil. Ancestry had no effect.

PMID- 24891769
TI  - Complexities of bloom dynamics in the toxic dinoflagellate Alexandrium fundyense
      revealed through DNA measurements by imaging flow cytometry coupled with species
      specific rRNA probes.
AB  - Measurements of the DNA content of different protist populations can shed light
      on a variety of processes, including cell division, sex, prey ingestion, and
      parasite invasion. Here, we modified an Imaging FlowCytobot (IFCB), a custom
      built flow cytometer that records images of microplankton, to measure the DNA
      content of large dinoflagellates and other high-DNA content species. The IFCB was
      also configured to measure fluorescence from Cy3-labeled rRNA probes, aiding the
      identification of Alexandrium fundyense (syn. A. tamarense Group I), a
      photosynthetic dinoflagellate that causes paralytic shellfish poisoning (PSP).
      The modified IFCB was used to analyze samples from the development, peak and
      termination phases of an inshore A. fundyense bloom (Salt Pond, Eastham, MA USA),
      and from a rare A. fundyense 'red tide' that occurred in the western Gulf of
      Maine, offshore of Portsmouth, NH (USA). Diploid or G2 phase ('2C') A. fundyense
      cells were frequently enriched at the near-surface, suggesting an important role
      for aggregation at the air-sea interface during sexual events. Also, our analysis
      showed that large proportions of A. fundyense cells in both the Salt Pond and red
      tide blooms were planozygotes during bloom decline, highlighting the importance
      of sexual fusion to bloom termination. At Salt Pond, bloom decline also coincided
      with a dramatic rise in infections by the parasite genus Amoebophrya. The samples
      that were most heavily infected contained many large cells with higher DNA
      associated fluorescence than 2C vegetative cells, but these cells' nuclei were
      also frequently consumed by Amoebophrya trophonts. Neither large cell size nor
      increased DNA-associated fluorescence could be replicated by infecting an A.
      fundyense culture of vegetative cells. Therefore we attribute these
      characteristics of the large Salt Pond cells to planozygote maturation rather
      than Amoebophrya infection, though an interaction between infection and
      planozygote maturation may also have contributed. The modified IFCB is a valuable
      tool for exploring the conditions that promote sexual transitions by
      dinoflagellate blooms but care is needed when interpreting results from samples
      in which parasitism is prevalent.

PMID- 24891768
TI  - Glutamine supplementation attenuates expressions of adhesion molecules and
      chemokine receptors on T cells in a murine model of acute colitis.
AB  - BACKGROUND: Migration of T cells into the colon plays a major role in the
      pathogenesis in inflammatory bowel disease. This study investigated the effects
      of glutamine (Gln) supplementation on chemokine receptors and adhesion molecules
      expressed by T cells in mice with dextran sulfate sodium- (DSS-) induced colitis.
      METHODS: C57BL/6 mice were fed either a standard diet or a Gln diet replacing 25%
      of the total nitrogen. After being fed the diets for 5 days, half of the mice
      from both groups were given 1.5% DSS in drinking water to induce colitis. Mice
      were killed after 5 days of DSS exposure. RESULTS: DSS colitis resulted in higher
      expression levels of P-selectin glycoprotein ligand- (PSGL-) 1, leukocyte
      function-associated antigen- (LFA-) 1, and C-C chemokine receptor type 9 (CCR9)
      by T helper (Th) and cytotoxic T (Tc) cells, and mRNA levels of endothelial
      adhesion molecules in colons were upregulated. Gln supplementation decreased
      expressions of PSGL-1, LFA-1, and CCR9 by Th cells. Colonic gene expressions of
      endothelial adhesion molecules were also lower in Gln-colitis mice. Histological
      finding showed that colon infiltrating Th cells were less in the DSS group with
      Gln administration. CONCLUSIONS: Gln supplementation may ameliorate the
      inflammation of colitis possibly via suppression of T cell migration.

PMID- 24891770
TI  - Study of two techniques for midline laparotomy fascial wound closure.
AB  - To study the results of two techniques, simple interrupted closure and continuous
      with intermittent Aberdeen knot technique for midline laparotomy fascial wound
      closure. A random selection of 200 midline laparotomy cases was done. In one
      group (group A) of 100 cases, midline fascial wound closure was done with
      continuous sutures with intermittent Aberdeen knot technique using Prolene No. 1
      suture material. In the other group (group B) of 100 cases, closure was done with
      the technique of simple interrupted sutures with Prolene No.1 suture material.
      Comparison of both the techniques regarding preoperative status and postoperative
      complication such as incisional hernia, wound dehiscence, suture sinus formation,
      stitch granuloma, and chronic wound pain was done according to clinical
      examination and recorded in the pro forma prepared. In group A, postoperative
      complications were incisional hernia 3 %, wound dehiscence 4 %, and suture sinus
      formation 1 %. In group B, postoperative complication were incisional hernia 5 %,
      wound dehiscence 4 %, and suture sinus formation 1 %. All these complications
      were statistically insignificant, in both group comparisons. While the
      complication such as stitch granuloma 3 %, chronic wound pain 3 %, and wound
      infection 4 % in group A was significantly less than in group B where the
      complication of stitch granuloma was 12 %, chronic wound pain 13 %, and wound
      infection 13 % (P value 0.03, P value 0.018, and P value 0.048, respectively).
      Both the techniques, simple interrupted suture closure and continuous with
      intermittent Aberdeen knot closure for midline laparotomy fascial wounds, show a
      similar rate of postoperative complication such as incisional hernia, wound
      dehiscence, and suture sinus formation. But the continuous suturing with
      intermittent Aberdeen knot technique is a better option to prevent complications
      such as stitch granuloma, chronic wound pain, and wound infection, which are
      higher in the simple interrupted fascial wound closure technique. 

PMID- 24891771
TI  - Consequences of spilt gallstones during laparoscopic cholecystectomy.
AB  - To document the incidence of spilt gallstones during laparoscopic
      cholecystectomy, the cause and consequences of such spillage. The study included
      150 consecutive laparoscopic cholecystectomies performed between October 2007 and
      November 2008. Data was collected in a prospective manner in accordance to
      proforma. Follow up were performed at the end of 1 week, 1 month, 6 months and 1
      year. The spillage of gall stones during surgery occurred in 19.04 % of the
      cases. Majority of the spillage occurred due to perforation of the gall bladder
      during dissection, followed by application of toothed grasper. Although all
      visible spilt stones were retrieved during surgery, complication rate of 0.66 %
      was observed. The incidence and complications secondary to the spillage of gall
      stones during standard laparoscopic cholecystectomy is low but avoidable. Various
      complications can occur, over a large period of time. Thus it is advisable to
      retrieve as many gallstones as possible short of converting to a laparotomy
      Dasari and Loan (JSLS 13(1):73-76, 2009), Daradkeh and Suwan (World J Surg 22:75
      77, 1998). 

PMID- 24891772
TI  - The unusual volvulus : a five year retrospective analysis of nine cases.
AB  - The ileosigmoid knot is a rare surgical emergency. It is an unusual type of bowel
      obstruction in which the ileum usually wraps around the base of the sigmoid colon
      and forms a pseudoknot. It is usually associated with difficult preoperative
      diagnosis and poor surgical outcome. To analyze the clinical presentations,
      operative findings, management, postoperative complications and outcome of
      patients with ileosigmoid knotting. A retrospective analysis of nine cases of
      ileosigmoid knotting over a 6-year period from July 2005 to May 2011. Ileosigmoid
      knotting was common in males in the fifth decade. Mean duration of symptoms prior
      to admission was 42.67 h. Both the ileum and the sigmoid colon were gangrenous in
      all the patients. Mortality was 22.22 %. The mean duration of hospital stay was
      13.67 days. To conclude, ileosigmoid knotting, though a rare cause of intestinal
      obstruction, carries a significant risk of mortality. In our study, ileostomy
      along with colorectal anastomosis seemed to be a better and safer alternative
      than primary repair in the management of ileosigmoid knotting. Awareness of this
      condition among surgeons will help to reduce the morbidity and mortality
      associated with this unusual form of intestinal obstruction. 

PMID- 24891773
TI  - Squamous cell carcinoma: morphological & topographical spectrum: a two year
      analysis.
AB  - Squamous cell carcinoma, which is a malignant tumor of the squamous epithelium,
      has been a major cause of morbidity and mortality worldwide. It is a major health
      problem across the world and among the most common cancers seen in both Indian
      men and women as can be gauged from the records of the National Cancer Registry
      Programme. This study was undertaken to analyze the spectrum of squamous cell
      carcinoma cases presenting at M.Y. Hospital, Indore, during 2 years between 2007
      and 2008, to understand the morphological patterns of squamous cell carcinoma
      lesions and classify them into morphological categories given by International
      Classification of Diseases for Oncology (ICD-O, third edition), to analyze the
      anatomical site distribution pattern of squamous cell carcinoma lesions and
      categorize them in topographical classes given by ICD-O. Over a 2-year period,
      959 cases were retrieved from the files of histopathology laboratory, department
      of pathology, M.G.M. Medical College, Indore. Out of total 959 cases, the maximum
      cases-290 (30.24 %)-of squamous cell carcinoma were found between the fourth and
      fifth decades of life. The frequency of squamous cell carcinoma in patients older
      than 30 years was 96.35 %, while in cases of less than 30 years, it was 03.65 %.
      Most of the reported cases of squamous cell carcinoma included invasive types
      (i.e., 94.3 %). Cases with distant metastasis constituted 4.7 %, while only 1 %
      were noninvasive or in situ. The frequency of squamous cell carcinoma presenting
      at our institution was highest among those involving the lip, oral cavity, and
      pharynx (56.50 %), followed by those involving female genital organs (30.24 %).
      The respective involvement of skin, digestive organs, and respiratory systems was
      4.70, 3.86, and 2.40 % in decreasing order of frequency. Frequency was least
      (1.05 %) among the cases reported to show metastatic deposits of squamous cell
      carcinoma in lymph nodes. Regarding the topographical spectrum, the maximum
      number of cases (26.07 %) of squamous cell carcinoma encountered belonged to ICD
      O category C-53 (i.e., cervix). Among the morphological categories, the most
      frequently encountered was that of squamous cell carcinoma, keratinizing (35.2
      %). 

PMID- 24891774
TI  - Effect of leptin and apelin preconditioning on hepatic ischemia reperfusion
      injury in rats.
AB  - Leptin and apelin are important adipocytokines involved in a variety of endocrine
      and paracrine functions. The aim of this study was to evaluate the effect of
      exogenous leptin and apelin preconditioning on hepatic ischemia reperfusion (I/R)
      injury in rats. Forty mice were assigned to four groups (n = 10): sham-operated
      control (sham), I/R injury, I/R + leptin (I/R + L), and I/R + apelin (I/R + A).
      Leptin 100 MUg/kg/day and apelin 2 MUg/kg/day were delivered intraperitoneally
      starting 3 days prior to surgical procedure in I/R + L and I/R + A groups,
      respectively. All I/R groups underwent 45 min of warm ischemia, followed by 30
      min of reperfusion. Serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), liver malondialdehyde (MDA) and glutathione (GSH), and
      liver histopathology were compared between groups. MDA was elevated in I/R, but
      stayed similar in I/R + L and I/R + A compared to sham. I/R + A had significantly
      lower MDA compared to I/R. GSH levels did not differ significantly between the
      groups. ALT and AST were elevated in all I/R groups, but significant reduction
      was observed in I/R + L and I/R + A compared to I/R. Liver histopathology was
      mostly mild in I/R + L and I/R + A, in contrast to severe injury observed in the
      I/R group. Leptin and apelin preconditioning significantly reduced hepatic I/R
      injury in rats. 

PMID- 24891775
TI  - Role of Subfascial Endoscopic Perforator Surgery (SEPS) in Management of
      Perforator Incompetence in Varicose Veins : A Prospective Randomised Study.
AB  - The study was carried out to compare the efficacy of subfascial endoscopic
      perforator surgery (SEPS) and open subfascial ligation of perforators in varicose
      veins. This study was conducted on 100 patients of varicose veins from January
      2006 to December 2010. Clinical scoring and color Doppler were performed in all
      the patients before surgery. Patients were divided into two groups: Group A and
      Group B alternately. Management of the perforators was done by subfascial
      endoscopic perforator surgery (SEPS) in Group A and by open subfascial ligation
      of perforators in Group B. Fifty patients were treated in each group. All the
      patients underwent ligation of incompetent saphenofemoral junction with stripping
      of long saphenous veins wherever the junction was incompetent with multiple
      ligation of superficial prominent veins. SEPS was done by two-port method without
      any tourniquet or balloon dissector. Total numbers of perforators ligated were
      178 in Group A and 136 in Group B. Patients in both the groups got symptomatic
      relief of symptoms, but ulcer healing in 33 % patients in Group A was faster as
      compared to Group B. However, at 3 months of follow-up the ulcers healed in all
      the patients in both groups. Incidence of wound infection was higher in group B
      (16 %) as compared to group A (0 %). There were residual perforators in 8 % of
      patients on color Doppler at 3 months of follow-up in Group B while there was no
      residual incompetent perforator in Group A. Subfascial endoscopic perforator vein
      surgery is a safe and effective method for treating incompetent perforating
      veins. The number of perforators ligated in SEPS was more as compared to the open
      subfascial ligation group. Possibly some perforators may be missed on Doppler
      localization and missed ligation, which may be a cause of future recurrence in
      varicose veins. Early relief of symptoms in terms of ulcer healing was better in
      the SEPS group with less wound complication rate; however, all the ulcers healed
      in both the groups at 3 months of follow-up. Cosmetic results were equal in both
      the groups. Major advantage of SEPS was less incidence of wound complications and
      less incidence of residual incompetent perforators. Hence, SEPS should be added
      for the management of perforators along with conventional surgery in varicose
      veins. 

PMID- 24891776
TI  - Inguinal Hernia Repair via Application of Mesh in Front of and behind the Fascia
      Transversalis.
AB  - The aim of this study was to compare mesh placement in front of the fascia
      transversalis and behid the fascia transversalis via inguinal incision. We
      evaluated the results of 106 inguinal hernia cases treated with polypropylene
      mesh applied via the anterior approach between December 2004 and January 2010.
      Using the anterior approach, the mesh was placed preperitoneally behind the
      fascia transversalis in 51 of the patients, whereas in the other 55 patients the
      mesh was placed in front of the fascia transversalis. Mean duration of surgery
      was shorter in the patients in which the mesh was placed behind the fascia
      transversalis (60 min vs. 75 min) (P < 0.05). In all, 8 patients (7.5%) had
      postoperative complications, including hematoma (n = 4), seroma (n = 2), scrotal
      edema (n = 1), and orchitis (n = 1). There weren't any significant differences in
      the complication rate between the 2 groups of patients (P > 0.05). During a mean
      44-month follow-up period (range: 12-72 months), no recurrence was observed. In
      conclusion, there weren't any significant differences between the 2 methods of
      inguinal hernia repair, other than the duration of surgery. 

PMID- 24891777
TI  - Routine histopathologic examination of two common surgical specimens-appendix and
      gallbladder: is it a waste of expertise and hospital resources?
AB  - This study was undertaken to assess whether a routine histopathologic examination
      of two common surgical specimens (appendix and gallbladder) is needed and whether
      routine histopathologic examination has an impact on further management of
      patients. Histopathology reports of patients who had undergone appendicectomy and
      cholecystectomy, between 2006 and 2010, were analyzed retrospectively in the
      department of pathology of a tertiary care hospital. The case notes were
      retrieved in all cases of malignancies. Patients having a clinical diagnosis or
      suspicion of malignancy were excluded. The incidence and impact of unexpected
      pathologic diagnosis on postoperative management were noted. The study period
      included a total of 1,123 and 711 appendicectomy and cholecystectomy specimens,
      respectively. Fifteen (1.336 %) cases of appendicectomy specimens revealed
      incidental unexpected pathological diagnoses, which included tubercular
      appendicitis (n = 2), parasite (n = 8), neuroma (n = 1), carcinoid (n = 2),
      pseudomyxoma (n = 1), and adenocarcinoma (n = 1). About 88 % of such unexpected
      appendiceal findings had an impact on postoperative treatment. Unexpected
      pathologic gallbladder findings were found in 12 (1.68 %) of 711 cholecystectomy
      specimens. In 6 (0.84 %) cases, gallbladder cancer (GBC) was detected. Additional
      further management was required in 50 % of patients with unexpected gallbladder
      findings. Twenty of the total 1,834 specimens (1.090 %) had an impact on patient
      management or outcome and were not suspected on macroscopic examination at the
      time of surgery. These would have been missed had the specimens not been examined
      microscopically. The intraoperative diagnosis of the surgeon is therefore
      sometimes doubtful in detecting abnormalities of the appendix and gallbladder.
      This study supports the sending of all appendicectomy and cholecystectomy
      specimens for routine histopathological examination. Appendix and gallbladder
      should undergo routine histopathological examination. This is important in
      patients with advanced age and gallstones. Also, it is of great value in
      identifying unsuspected conditions which require further postoperative
      management. Selectively sending specimens for histopathological examination can
      result in reduced workload on the histopathology department without compromising
      patient safety. 

PMID- 24891778
TI  - Vesicovaginal fistula: diagnosis and management.
AB  - Vesicovaginal fistula (VVF) is still a major cause for concern in many developing
      countries. It represents a significant morbidity in female urology. Continual
      wetness, odor, and discomfort cause serious social problems. The diagnosis of the
      condition has traditionally been based on clinical methods and dye testing. A
      successful repair of such fistulas requires an accurate diagnostic evaluation and
      timely repair using procedures that exploit basic surgical principles and the
      application of interposition flaps. The method of closure depends on the
      surgeon's training and experience. The main complication of VVF surgery is
      recurrent fistula formation. 

PMID- 24891779
TI  - Preduodenal portal vein in adult with polysplenia syndrome revisited with a case
      report.
AB  - Preduodenal portal vein (PDPV) is a rare developmental anomaly. In infants, this
      is often associated with duodenal obstruction or biliary atresia. It is generally
      asymptomatic in adults (Ooshima et al., Hepato-Biliary-Pancreat Surg 5(4):455
      458, 1998). Here, we report a singular case of adult PDPV that was discovered
      accidentally during emergency laparotomy for peritonitis due to gastric
      perforation in a 38-year-old lady. A plethora of congenital anomalies was
      uncovered, which is consistent with the reported cases of classical polysplenia
      syndrome, viz., multiple spleens of equal volume, visceral heterotaxia, right
      (Rt.)-sided stomach, a left (Lt.)-sided or a large midline liver, malrotation of
      intestine, a short pancreas, PDPV and IVC abnormalities (Gayer et al., Abdom
      Imaging 24:178-184, 1999). In addition, abnormalities like anamolous origin of
      Lt. gastric and splenic arteries from the abdominal aorta with absent celiac
      trunk, hepatic artery arising from the superior mesenteric artery, hepatic veins
      draining directly to Rt. atrium, etc. along with hypertrophic and lipomatous
      interatrial septum have also been detected during further investigations. As of
      now, we have come across 29 cases of adult PDPV reported in world literature and
      we are reporting our unique case with a review of literature on anomalies of
      visceral organs associated with PDPV. 

PMID- 24891780
TI  - A large cutaneous horn of the glans penis: a rare presentation.
AB  - Cutaneous horn (cornu cutaneum) is a relatively uncommon lesion consisting of a
      projectile, conical, dense, hyperkeratotic nodule which resembles the horn of an
      animal. Cutaneous horns most frequently occur in sun-exposed parts and are
      typically found in the face and the scalp, but may also occur on the hands,
      eyelids, nose, chest, neck, shoulder and penis. Their occurrence on the penis is
      uncommon. We report a 42-year-old man presenting with penile cutaneous horn. The
      association with malignancy on the penis makes proper identification of these
      lesions essential. Standard treatment involves local excision, but the presence
      of malignancy mandates a partial penectomy. 

PMID- 24891781
TI  - Primary Grynfeltt's Hernia.
AB  - Lumbar hernia is a rare defect of the abdominal wall. It accounts for 2 % of all
      wall hernias. It is divided in two levels: superior lumbar hernia, also known as
      Grynfeltt's hernia (GH), and an inferior lumbar hernia or Petit's hernia. GH is
      more commonly encountered in practice, and it is mainly posttraumatic in origin.
      Spontaneous primary GH is quite rare. Only 250 to 300 of such cases have been
      reported the in literature so far. The treatment of choice is retroperitoneal
      surgical approach and a meshplasty after complete reduction of its contents.
      Prognosis is usually excellent. 

PMID- 24891782
TI  - Strangulated small bowel obstruction secondary to a transmesosigmoid hernia.
AB  - Internal hernias are an infrequent cause of small bowel obstruction with
      transmesosigmoid herniation being very rare, especially in patients with no
      history of abdominal surgery or trauma. Early surgical intervention is important
      in acute presentation to reduce the high morbidity and mortality rates associated
      with this disease. 

PMID- 24891783
TI  - Midgut volvulus induced extensive bowel infarction.
AB  - Midgut volvulus, mostly occurs due to congenital midgut malrotation, has been
      reported as a rare but lethal complication of some acquired medical conditions,
      such as postoperative adhesion bands, tumors, and mesenteric cysts. It is a
      surgical emergency to cause extensive bowel ischemia resulted from torsion of
      superior mesenteric artery. Early diagnosis and intervention is the only manner
      to prevent extended bowel necrosis. Here, we report a case of midgut volvulus
      with typical computed tomography features-the whirl sign, the transposition of
      the superior mesenteric artery and vein, and the ischemic change of bowel
      supplied by superior mesenteric artery. Early operation prevented the fate of
      extended bowel resection. 

PMID- 24891785
TI  - A rare stoma-related complication: parastomal evisceration.
AB  - Defunctioning stoma is a commonly used colorectal surgical procedures. The stomal
      complications recorded are usually classified as early and late complications.
      Parastomal hernia is a common complication of stomal surgery. We present a very
      rare stoma-related complication developed after parastomal hernia and described
      parastomal evisceration. 

PMID- 24891784
TI  - Jejunojejunal intussusception with internal herniation in the stomach.
AB  - Jejunojejunal intussusception with internal herniation of the stomach through a
      gastrojejunostomy stoma is one of the rarest complications of the previous
      gastric surgery. The incidence is reported to be less than 0.1 %. An elderly male
      presented to the emergency room with signs of intestinal obstruction for 1 day.
      There was also history of appearance of a lump in the mid-abdomen. A primarily
      healed midline scar of the previous surgery was present; the details of which
      were not known. X ray abdomen in the erect posture showed multiple air fluid
      levels. Ultrasonography (USG) revealed dilated stomach with central
      hyperechogenicity with a peripheral rim of decreased echogenecity. Contrast
      enhanced computed tomography (CECT) scan showed jejunojejunal intussusception
      with internal herniation of the stomach. On laparotomy, it was found that there
      was a previous gastrojejunostomy with jejunal invagination leading to gangrene of
      a segment. Resection anastomosis was done. The postoperative period was
      uneventful. 

PMID- 24891786
TI  - Congenital urethrocutaneous fistula-our experience with nine cases.
AB  - Congenital urethrocutaneous fistula is a very rare anomaly with about 40 odd
      cases reported in literature till 2008 .We present here 9 such cases all of whom
      were uncircumcised at presentation.7 out of 9 cases had a fistula in the distal
      shaft and the rest 2 cases had a fistula in the mid-shaft of the penis with an
      associated chordee.Associated congenital anomaly was present in only one case
      which had an associated imperforate anus . When the fistula was present distally
      , we did a primary repair of the fistula which was reinforced by a Bayer's Flap.
      When the fistula was present in the mid shaft we did a Primary repair of the
      fistula & reinforced it by a Tunica Vaginalis Flap. 

PMID- 24891787
TI  - Anatomic liver resection of segments 6, 7, and 8 by the method of selective
      occlusion of hepatic inflow.
AB  - Anatomic liver resection not only enables enough tumor-free resection margin but
      also guarantees maximum preservation of remaining normal liver tissue. We report
      herein a hepatocellular carcinoma patient who underwent successful anatomic liver
      resection of segments 6, 7, and 8 by the method of selective occlusion of hepatic
      inflow. Multiple tumors were found in segments 6, 7, and 8 by computed
      tomographic (CT) scanning. CT volumetry analyzed that his left hemi-liver volume
      was less than the minimal limit of safe survival. Therefore, we planned to
      perform segment 5 remaining, anatomic liver resection of segments 6, 7, and 8 to
      guarantee the maximum preservation of remaining normal liver tissue. Selective
      occlusion of hepatic inflow was creatively used twice in this case to divide
      right hemi-liver Glissonean pedicle and segments 6 and 7 Glissonean pedicle,
      respectively. Thus, the resection line was determined, and anatomic liver
      resection of segments 6, 7, and 8 was completed. Selective right hemi-liver
      Glissonean pedicle occlusion was used, while parenchymal transection was between
      segments 6 and 5 and between segments 8 and 5. Therefore, liver ischemia
      reperfusion injury and homodynamic instability were maximally reduced during
      operation. 

PMID- 24891788
TI  - VAC Therapy in Large Infected Sacral Pressure Ulcer Grade IV-Can Be an
      Alternative to Flap Reconstruction?
AB  - Vacuum-assisted closure (VAC) therapy is a new entrant in wound care after growth
      factors and alginate or hydrocolloid dressing, in the treatment of pressure
      ulcers. We have been using this technique for diabetic foot ulcers. A young
      nondiabetic man presented with a large sacral bed sore after high doses of
      ionotropes in an intensive care unit for treating severe hypotension. His wound
      was debrided, and instead of flap surgery in such infected wound, he was treated
      with VAC therapy. The complete wound healing was achieved in 6 weeks and at half
      the cost of flap surgery. Moreover, the chances of flap failure and its related
      complications were eliminated. 

PMID- 24891789
TI  - Anterolateral Thigh Twin Free Flaps from a Single Donor Site-a Modification Based
      on the Oblique Branch of the Lateral Circumflex Femoral Artery.
AB  - The pedicle of the anterolateral thigh flap is formed by the descending branch of
      the lateral circumflex femoral artery. Recently, an oblique branch of lateral
      circumflex femoral artery was described by Wei et al., which can also be used as
      an alternative to the descending branch. We describe a case in which both the
      pedicles were used to create two free flaps (twin flaps) from the same thigh for
      post tumour reconstruction of breast. 

PMID- 24891790
TI  - Prevention of gossypiboma.

PMID- 24891791
TI  - Writing a research article. Are we ignoring the basics?

PMID- 24891792
TI  - One-stage repair of proximal hypospadias using lateral penile flap-preliminary
      results in a single-center experience.

PMID- 24891793
TI  - Late prof. J. K. Trivedi: a teacher affects eternity.

PMID- 24891795
TI  - Preface MSM 2014.

PMID- 24891794
TI  - Late j. K. Trivedi: a noble soul and a great human being.

PMID- 24891796
TI  - What explains consciousness? Or...What consciousness explains?
AB  - In this invited commentary I focus on the topic addressed in three papers: De
      Sousa's (2013[1617]) Toward an Integrative Theory of Consciousness, a monograph
      with Parts 1 & 2, as well as commentaries by Pereira (2013a[59]) and Hirstein
      (2013[42]). All three are impressively scholarly and can stand-and shout-on their
      own. But theory of consciousness? My aim is to slice that topic into the two
      fundamentally different kinds of theories of consciousness, say what appears to
      be an ideology, out of behaviourism into cognitivism, now also influencing the
      quest for an "explanation of consciousness" in cognitive neuroscience. I will
      then say what can be expected given what we know of the complexity of brain
      structure, the richness of a conscious "vocabulary", and current technological
      limits of brain imaging. This will then turn to the strategy for examining "what
      consciousness explains"-metatheory, theories, mappings, and a methodology of
      competitive support, a methodology especially important where there are competing
      commitments. There are also increasingly common identifications of methodological
      bias in, along with failures to replicate, studies reporting unconscious controls
      in decision, social priming-as there have been in perception, learning, problem
      solving, etc. The literature critique has provided evidence taken as reducing,
      and in some cases eliminating, a role for conscious controls-a position
      consistent with that ideology out of behaviourism into cognitivism. It is an
      ideological position that fails to recognize the fundamental distinction between
      theoretical and metaphysical assertions. 

PMID- 24891798
TI  - Speaking to a Wider Audience about the Positive Contributions of Psychiatry.
AB  - We live in a world that is increasingly complex, intense, and stressful. Most
      people, at some time or other in their lives, can make good use of psychiatry as
      they map their course and steer their way through it. While this holds true,
      there also exists a very disturbing trend. No other branch of medicine suffers a
      similar, constant criticism, scrutiny and quite often downright vehement protest.
      Even the service users, who have been greatly benefitted, choose to stay mum for
      fear of stigmatization that may follow if they admit to have undergone therapy.
      The onus lies on both, the service users and providers alike, to take the
      positive contributions of psychiatry to the masses at large. All of us,
      especially medical professionals, need to consider our own attitudes and
      awareness. The recognition that anyone will break down if mental stress is high
      enough should help free us from a 'them and us' attitude. Reading about people's
      own experience of mental illness can promote understanding: Examples include a
      successful actress and a prize-winning author. For mental health practitioners,
      enabling service users to influence service development is another strong anti
      stigma move. A cognitive behavior therapy approach can help individuals overcome
      the stigma felt and also cope better with discrimination. Also, we need to stand
      up against mental health discrimination wherever it is encountered. 

PMID- 24891797
TI  - The Task before Psychiatry Today Redux: STSPIR*.
AB  - This paper outlines six important tasks for psychiatry today, which can be put in
      short as: Spread and scale up services;Talk;Science,Psychotherapy;Integrate;
      andResearch excellence. As an acronym, STSPIR. Spread and scale up services:
      Spreading mental health services to uncovered areas, and increasing facilities in
      covered areas:Mental disorders are leading cause of ill health but bottom of
      health agenda;Patients face widespread discrimination, human rights violations
      and lack of facilities;Need to stem the brain drain from developing countries;At
      any given point, 10% of the adult population report having some mental or
      behavioural disorder;In India, serious mental disorders affect nearly 80 million
      people, i.e. combined population of the northern top of India, including Punjab,
      Haryana, Jammu and Kashmir, Uttarakhand and Himachal Pradesh;Combating imbalance
      between burden of demand and supply of efficient psychiatric services in all
      countries, especially in developing ones like India, is the first task before
      psychiatry today. If ever a greater role for activism were needed, this is the
      field;The need is to scale up effective and cost-effective treatments and
      preventive interventions for mental disorders.TALK: Speaking to a wider audience
      about positive contributions of psychiatry:Being aware of, understanding, and
      countering, the massive anti-psychiatry propaganda online and elsewhere;Giving a
      firm answer to anti-psychiatry even while understanding its transformation into
      mental health consumerism and opposition to reckless medicalisation;Defining
      normality and abnormality;Bringing about greater precision in diagnosis and
      care;Motivating those helped by psychiatry to speak up;Setting up informative
      websites and organising programmes to reduce stigma and spread mental health
      awareness;Setting up regular columns in psychiatry journals around the globe,
      called 'Patients Speak', or something similar, wherein those who have been helped
      get a chance to voice their stories.SCIENCE: Shrugging ambivalence and
      disagreement and searching for commonalities in psychiatric phenomena;An
      idiographic orientation which stresses individuality cannot, and should not,
      preclude the nomothetic or norm laying thrust that is the crux of scientific
      progress.The major contribution of science has been to recognize such
      commonalities so they can be researched, categorized and used for human
      welfare.It is a mistake to stress individuality so much that commonalities are
      obliterated.While the purpose and approach of psychiatry, as of all medicine, has
      to be humane and caring, therapeutic advancements and aetiologic understandings
      are going to result only from a scientific methodology.Just caring is not enough,
      if you have not mastered the methods of care, which only science can
      supply.PSYCHOTHERAPY: Psychiatrists continuing to do psychotherapy:Psychotherapy
      must be clearly defined, its parameters and methods firmly delineated, its proof
      of effectiveness convincingly demonstrated by evidence based and controlled
      trials;Psychotherapy research suffers from neglect by the mainstream at present,
      because of the ascendancy of biological psychiatry;It suffers resource
      constraints as major sponsors like pharma not interested;Needs funding from some
      sincere researcher organisations and altruistic sponsors, as also professional
      societies and governments;Psychotherapy research will have to provide enough
      irrefutable evidence that it works, with replicable studies that prove it across
      geographical areas;It will not do for psychiatrists to hand over psychotherapy to
      clinical psychologists and others.INTEGRATE APPROACHES: Welcoming biological
      breakthroughs, while supplying psychosocial insights:Experimental breakthroughs,
      both in aetiology and therapeutics, will come mainly from biology, but the
      insights and leads can hopefully come from many other fields, especially the
      psychosocial and philosophical;The biological and the psychological are not
      exclusive but complementary approaches;Both integration and reductionism are
      valid. Integration is necessary as an attitude, reductionism is necessary as an
      approach. Both the biological and the psychosocial must co-exist in the
      individual psychiatrist, as much as the branch itself.RESEARCH EXCELLENCE:
      Promoting genuine research alone, and working towards an Indian Nobel Laureate in
      psychiatry by 2020:To stop promoting poor quality research and researchers, and
      to stop encouraging sycophants and ladder climbers. To pick up and hone genuine
      research talent from among faculty and students;Developing consistent quality
      environs in departments and having Heads of Units who recognize, hone and nurture
      talent. And who never give in to pessimism and cynicism;Stop being satisfied with
      the money, power and prestige that comes by wheeling-dealing, groupism and
      politicking;Infinite vistas of opportunity wait in the wings to unfold and offer
      opportunities for unravelling the mysteries of the 'mind' to the earnest seeker.
      Provided he is ready to seek the valuable. Provided he stops holding on to the
      artificial and the superfluous. 

PMID- 24891799
TI  - Welcome biological breakthroughs, supply psychosocial insights.
AB  - Human behaviour, emotions, and cognition are complex to understand and explain.
      It is even more difficult to understand the basis for abnormal behaviour,
      disturbed emotions, and impaired cognitions, something mental health
      professionals are trying for long. In these pursuits, psychiatry has traversed
      through eras of humours, witchcraft, spirits, psychoanalysis, and gradually
      deviated from other medical specialities. Now, with recent biological
      breakthroughs like advances in psychopharmacology, neuroimaging and genetics,
      increasingly more emphasis is being given to the biological model of psychiatric
      disorders. These new biological models have given a more scientific appearance to
      the speciality. It has also revolutionised the management strategies and outcome
      of many psychiatric disorders. However, this rapid development in biological
      understanding of psychiatry also leads to a new wave of reductionism. In an
      attempt to deduce everything in terms of neurons, neurochemicals, and genes, can
      we neglect psychosocial aspects of mental health? Patients' personality,
      expectations, motives, family background, sociocultural backgrounds continue to
      affect mental health no matter how much 'biological' psychiatry gets. Biological
      and psychosocial approaches are not mutually exclusive but complementary.
      Integrating them harmoniously is the skill psychiatry demands for comprehensive
      understanding of mental and behavioural disorders. 

PMID- 24891800
TI  - Shrug ambivalence and disagreement; search commonalities in psychiatric
      phenomena(**).
AB  - Holistic understanding is necessary to study intimate nuances of
      psychological/psychopathological processes; also, individual manifestations and
      individual approach are laudable goals in treatment and approach. But we cannot
      forget that major therapeutic advances result when we are able to delineate
      commonalities and stable symptom clusters that cut across geo-cultural boundaries
      and are amenable to study and intervention. Even though the purpose and approach
      of psychiatry, as of all medicine, has to be humane and caring, major therapeutic
      advancements and aetiologic understandings result only from a scientific
      methodology that stresses and figures out the commonalities of psychopathological
      phenomena. It is a mistake to stress individuality so much that commonalities are
      obliterated. Although stress on the individual's needs has helped psychiatry at
      times become more humane, it has hurt the task enormously by making some very
      bright minds question the very scientific basis of psychiatry and its status as a
      medical discipline. Hence, even as it is necessary to promote holistic and
      individualistic caring, it is equally necessary to shrug ambivalence and
      crippling disagreements that can result if individualism in therapy is carried
      beyond limits. Psychiatry's tradition, and field, will always allow for diversity
      in its practice, even in its theorising. For, psychopathology has both a
      personal, deep inner dimension - due to biogenetic and personality factors - and
      social, manifest/unmanifest, outer dimension - due to the environment. And the
      practice, and theory, of both are likely to be different, although we do try to
      amalgamate them in our 'bio-psycho-social' model. Such differences are only
      manifestations of an intricate network of influences that make for the human
      condition in health and disease. Psychiatry is the one branch which realises this
      diversity the most, but equally important for it is to stress its unity: Of
      purpose - that of reducing individual and social psychopathology;Of goals - that
      of unravelling the aetiopathology of psychiatric disorders; finding precision in
      diagnostics and investigative tests; finding biomarkers; and finding precise
      therapies for precise disorders that control such disorders; and not just
      control, but finally cure them; finding methods of primary prevention; of moving
      from mental disorder to mental health; and, further, of progress to individual
      actualisation and personal and collective well-being with longevity;Of practice -
      a) in therapy: By synergising psychopharmacology/somatic therapies with
      psychotherapy/therapies, social therapies and pharmacogenetics; b) in
      diagnostics: By identifying the phenotype-genotype-endophenotype axis; and (c) by
      promoting such therapy and diagnostics as brings about control, and finally,
      cure/primary prevention of psychiatric disorders.The future course for psychiatry
      involves a goal oriented forward movement - while allowing for diversity in
      practice and theory, stressing on unity of purpose, goals, and practice. 

PMID- 24891801
TI  - Medicine and Mind-Body Dualism: A Reply to Mehta's Critique.
AB  - Neeta Mehta recently advanced the thesis that medical practice is facing a crisis
      today. In her paper "Mind-body dualism: a critique from a health perspective" she
      attributes the crisis to the philosophy of Descartes and set out to understand
      why this dualism is still alive despite its disavowal from philosophers, health
      practitioners and lay people. The aim of my reply to her critique is three-fold.
      First, I draw attention to a more fundamental problem and show that dualism is
      inescapable-scientifically and commonsensically. I then focus on the self
      conscious emotions of shame, guilt and remorse, and argue that the self is not
      identical with a brain. The third section draws attention to the crisis in
      psychiatry and stipulates some of the main reasons why this is so. Contrary to
      Mehta's thesis, the health profession faces a crisis because of physicalism and
      biological reductionism. 

PMID- 24891802
TI  - Natural evolution and human consciousness.
AB  - A visual conscious experience is my empirical basis. All that we know comes to us
      through conscious experiences. Thanks to natural evolution, we have nearly direct
      perception, and can largely trust the information we attain. There is full
      integration, with no gaps, of organisms in the continuous world. Human conscious
      experiences, on the other hand, are discrete. Consciousness has certain limits
      for its resolution. This is illustrated by the so-called light-cone, with
      consequences for foundations in physics. Traditional universals are replaced by
      feels and distributions. Conscious experiences can be ordered within a framework
      of conceptual spaces. Triple Aspect Monism (TAM) can represent the dynamics of
      conscious systems. However, to fully represent the creative power of human
      consciousness, an all-inclusive view is suggested: Multi Aspect Monism (MAM). 

PMID- 24891803
TI  - Stress and its Expression According to Contemporary Science and Ancient Indian
      Wisdom: Perseverative Cognition and the Panca kosas.
AB  - Stress is recognised as the most challenging issue of modern times. Contemporary
      science has understood this phenomenon from one aspect and Indian philosophy
      gives its traditional reasons based on classical texts. Modern science has
      recently proposed a concept of perseverative cognition (PC) as an important
      reason for chronic stress. This has shown how constant rumination on an
      unpalatable event, object or person leads to various lifestyle disorders.
      Similarly classical yoga texts like the Taittiriya Upanishad, the Bhagavad Gita,
      and the Yoga Vashistha describe stress in their unique ways. We have here
      attempted a detailed classification, description, manifestation, and development
      of a disease and its management through these models. This paper in a nutshell
      projects these two models of stress and shows how they could be used in future
      for harmonious management of lifestyle disorders. 

PMID- 24891805
TI  - Consciousness.

PMID- 24891804
TI  - From here and now to infinity and eternity: a message to new medical doctors(*).
AB  - Commencement means both an end and a beginning; the end of the academic year and
      the beginning of the rest of your life as new physicians. For such a beginning,
      it is useful to view it in retrospect, from the point of view of the end, by
      conducting a pre-mortem on your life. Taking the existentialist (ex sistere, to
      stand forth) stance, each of us can be classified into one of four basic types of
      person, based on our characteristic space and time (or spatio-temporal) context
      or horizon. Our space can be limited to the "here" and our time to the "now;" or
      our space may extend to "infinity" and our time embark on "eternity." In-between
      these poles, most have space contexts rooted in their home and work "turf" and
      time involving their "lifetime," while some expand their space to include the
      "world" and their time to encompass "history." From the "here and now" and "turf
      and lifetime" contexts, the horizons of "world and history," and "infinity and
      eternity" are examined, challenging new medical doctors to realize their full
      potential. The new physician is exhorted not to wait for a post-mortem to define
      (des finitus, to set limits) his or her life. He or she should stand forth, to
      live, and give life. The new medical doctor is encouraged to look to the sunrise,
      draw strength from the sunshine, to be brave, and strong and true. 

PMID- 24891807
TI  - Peer Reviewers for MSM 2014.

PMID- 24891806
TI  - Corrections to my paper: john locke on personal identity.

PMID- 24891808
TI  - Template for MSM Submissions.

PMID- 24891809
TI  - Linking Decisions and Actions in Dynamic Environments: How Child and Adult
      Cyclists Cross Roads With Traffic.
AB  - Unlike affordances involving stationary objects, affordances involving moving
      objects change over time. This means that actions must be tightly linked to
      decisions, making perceiving and acting on affordances involving moving objects
      challenging for children and adults alike. Here, we overview our program of
      research on how children and adults perceive and act on moving objects in the
      context of bicycling across roads in an immersive virtual environment. This work
      shows that although children attempt to adjust their actions to fit their risky
      decisions, they do not fully adjust their decisions to fit their action
      capabilities. This mismatch between child cyclists' decisions and actions may be
      a risk factor for car-bicycle collisions in late childhood and early adolescence.

PMID- 24891810
TI  - Effect of Indium Content on the Melting Point, Dross, and Oxidation
      Characteristics of Sn-2Ag-3Bi-xIn Solders.
AB  - This paper presents the effect of indium (In) content on the melting temperature,
      wettabililty, dross formation, and oxidation characteristics of the Sn-2Ag-3Bi
      xIn alloy. The melting temperature of the Sn-2Ag-3Bi-xIn alloy (2 <= x <= 6) was
      lower than 473 K. The melting range between the solidus and liquidus temperatures
      was approximately 20 K, irrespective of the indium content. As the indium content
      increased, the wetting time increased slightly and the maximum wetting force
      remained to be mostly constant. The dross formation decreased to approximately
      50% when adding 1In to Sn-2Ag-3Bi, and no dross formation was observed in the
      case of Sn-2Ag-3Bi-xIn alloy (x >= 1.5) at 523 K for 180 min. Upon approaching
      the inside of the oxidized solder of the Sn-2Ag-3Bi-1.5In alloy from the surface,
      the O and In contents decreased and the Sn content increased based on depth
      profiling analysis using Auger electron spectroscopy (AES). The mechanism for
      restraining dross (Sn oxidation) of Sn-2Ag-3Bi alloy with addition of indium may
      be due to surface segregation of indium. This is due to the lower formation
      energy of indium oxide than those of Sn oxidation.

PMID- 24891811
TI  - Reliability Assessment and Activation Energy Study of Au and Pd-Coated Cu Wires
      Post High Temperature Aging in Nanoscale Semiconductor Packaging.
AB  - Wearout reliability and high temperature storage life (HTSL) activation energy of
      Au and Pd-coated Cu (PdCu) ball bonds are useful technical information for Cu
      wire deployment in nanoscale semiconductor device packaging. This paper discusses
      the influence of wire type on the wearout reliability performance of Au and PdCu
      wire used in fine pitch BGA package after HTSL stress at various aging
      temperatures. Failure analysis has been conducted to identify the failure
      mechanism after HTSL wearout conditions for Au and PdCu ball bonds. Apparent
      activation energies (Eaa) of both wire types are investigated after HTSL test at
      150  degrees C, 175  degrees C and 200  degrees C aging temperatures. Arrhenius
      plot has been plotted for each ball bond types and the calculated Eaa of PdCu
      ball bond is 0.85 eV and 1.10 eV for Au ball bond in 110 nm semiconductor device.
      Obviously Au ball bond is identified with faster IMC formation rate with IMC
      Kirkendall voiding while PdCu wire exhibits equivalent wearout and or better
      wearout reliability margin compare to conventional Au wirebond. Lognormal plots
      have been established and its mean to failure (t50) have been discussed in this
      paper.

PMID- 24891813
TI  - A novel mutation in the NR2E3 gene associated with Goldmann-Favre syndrome and
      vasoproliferative tumor of the retina.
AB  - PURPOSE: Various autosomal recessive retinal dystrophies are reported to be
      associated with mutations in nuclear receptor subfamily 2, group E, member 3
      (NR2E3, also called PNR) gene. The present study proposed to understand the
      clinical and genetic characteristics of the family of a patient with an ocular
      phenotype consistent with Goldmann-Favre syndrome (GFS) and vasoproliferative
      tumors of the retina (VPTRs). METHODS: Twelve family members of the proband from
      three generations underwent complete ophthalmic examination, including best
      corrected visual acuity with Snellen optotypes, tonometry, biomicroscopic
      examination, indirect ophthalmoscopy after pupillary dilatation, computerized
      perimetry, optical coherence tomography, fundus photography, intravenous
      fluorescein angiography, and electroretinography (ERG). All the study subjects
      underwent genetic analysis of the entire coding region of the NR2E3 gene with the
      bidirectional DNA sequencing approach. Hundred healthy individuals were screened
      for the variant. RESULTS: The phenotype of the proband had features of GFS with
      VPTRs. The tumors showed complete resolution with cryotherapy and transpupillary
      thermotherapy (TTT). Sequencing of the entire coding region of the NR2E3 gene in
      the proband revealed a novel homozygous c.1117 A>G variant that led to the amino
      acid change from aspartic acid to glycine at position 406 (p.D406G). This change
      was present in the homozygous state in affected family members and in the
      heterozygous state in unaffected family members, and was undetectable in the
      control subjects. The identified novel p.D406G homozygous mutation was at an
      evolutionarily highly conserved region and may possibly affect the protein
      function (Sorting Intolerant From Tolerant [SIFT] score = 0.00). CONCLUSIONS:
      Patients with GFS may present with retinal VPTRs that respond to therapy with
      cryotherapy and TTT. Molecular genetic studies helped to identify a novel p.D406G
      mutation in the affected members, which will aid in confirming the diagnosis, for
      genetic counseling of family members and potentially provide some form of therapy
      for the affected patients.

PMID- 24891812
TI  - Effects on DNA Damage and/or Repair Processes as Biological Mechanisms Linking
      Psychological Stress to Cancer Risk.
AB  - Considerable research effort in the past several decades has focused on the
      impact of psychological stress, and stress hormones, on cancer progression.
      Numerous studies have reported that stress hormone treatment or in vivo stress
      exposure can enhance the growth of tumor cell lines in vitro, as well as tumors
      in animal models, and have begun to explore molecular mechanisms. Comparatively
      little research has focused on the impact of psychological stress and stress
      hormones on cancer initiation, in part due to inherent methodological challenges,
      but also because potential underlying biological mechanisms have remained
      obscure. In this review, we present a testable theoretical model of pathways by
      which stress may result in cellular transformation and tumorigenesis. This model
      supports our overarching hypothesis that psychological stress, acting through
      increased levels of catecholamines and/or cortisol, can increase DNA damage
      and/or reduce repair mechanisms, resulting in increased risk of DNA mutations
      leading to carcinogenesis. A better understanding of molecular pathways by which
      psychological stress can increase the risk of cancer initiation would open new
      avenues of translational research, bringing together psychologists,
      neuroscientists, and molecular biologists, potentially resulting in the
      development of novel approaches for cancer risk reduction at the population
      level.

PMID- 24891814
TI  - Diagnostic accuracy in detecting tears in the proximal biceps tendon using
      standard nonenhancing shoulder MRI.
AB  - BACKGROUND: There is a paucity of data in the literature evaluating the
      performance of noncontrast MRI in the diagnosis of partial and complete tears of
      the proximal portion of the long head of the biceps (LHB) tendon. The objective
      of this study was to evaluate the accuracy of noncontrast magnetic resonance
      imaging (MRI) compared to arthroscopy for the diagnosis of pathology involving
      the intra-articular portion of the LHB tendon. METHODS: We conducted a
      retrospective review of 66 patients (mean age 57.8 years, range 43-70 years) who
      underwent shoulder arthroscopy and evaluation of the LHB tendon after having had
      a noncontrast MRI of the shoulder. Biceps pathology was classified by both MRI
      and direct arthroscopic visualization as either normal, partial tearing, or
      complete rupture, and arthroscopy was considered to be the gold standard. We then
      determined the sensitivity, specificity, and positive- and negative-predictive
      values of MRI for the detection of partial and complete LHB tears. RESULTS: MRI
      identified 29/66 (43.9%) of patients as having a pathologic lesion of the LHB
      tendon (19 partial and ten complete tears) while diagnostic arthroscopy
      identified tears in 59/66 patients (89.4%; 50 partial and 16 complete). The
      sensitivity and specificity of MRI for detecting partial tearing of the LHB were
      27.7% and 84.2%, respectively (positive predictive value =81.2%, negative
      predictive value =32.0%). The sensitivity and specificity of MRI for complete
      tears of the LHB were 56.3% and 98.0%, respectively (positive predictive value
      =90.0%, negative predictive value =87.5%). CONCLUSION: Standard noncontrast MRI
      of the shoulder is limited in detecting partial tears and complete ruptures of
      the intra-articular LHB tendon. Surgeons may encounter pathologic lesions of the
      LHB tendon during arthroscopy that are not visualized on preoperative MRI.

PMID- 24891815
TI  - Using the power balance model to simulate cross-country skiing on varying
      terrain.
AB  - The current study adapts the power balance model to simulate cross-country skiing
      on varying terrain. We assumed that the skier's locomotive power at a self-chosen
      pace is a function of speed, which is impacted by friction, incline, air drag,
      and mass. An elite male skier's position along the track during ski skating was
      simulated and compared with his experimental data. As input values in the model,
      air drag and friction were estimated from the literature based on the skier's
      mass, snow conditions, and speed. We regard the fit as good, since the difference
      in racing time between simulations and measurements was 2 seconds of the 815
      seconds racing time, with acceptable fit both in uphill and downhill terrain.
      Using this model, we estimated the influence of changes in various factors such
      as air drag, friction, and body mass on performance. In conclusion, the power
      balance model with locomotive power as a function of speed was found to be a
      valid tool for analyzing performance in cross-country skiing. 

PMID- 24891816
TI  - Self-reported concussion history: impact of providing a definition of concussion.
AB  - BACKGROUND: In recent years, the understanding of concussion has evolved in the
      research and medical communities to include more subtle and transient symptoms.
      The accepted definition of concussion in these communities has reflected this
      change. However, it is unclear whether this shift is also reflected in the
      understanding of the athletic community. WHAT IS KNOWN ABOUT THE SUBJECT: Self
      reported concussion history is an inaccurate assessment of someone's lifetime
      exposure to concussive brain trauma. However, unfortunately, in many cases it is
      the only available tool. HYPOTHESIS/PURPOSE: We hypothesize that athletes' self
      reported concussion histories will be significantly greater after reading them
      the current definition of concussion, relative to the reporting when no
      definition was provided. An increase from baseline to post-definition response
      will suggest that athletes are unaware of the currently accepted medical
      definition. STUDY DESIGN: Cross-sectional study of 472 current and former
      athletes. METHODS: Investigators conducted structured telephone interviews with
      current and former athletes between January 2010 and January 2013, asking
      participants to report how many concussions they had received in their lives.
      Interviewers then read participants a current definition of concussion, and asked
      them to re-estimate based on that definition. RESULTS: THE TWO ESTIMATES WERE
      SIGNIFICANTLY DIFFERENT (WILCOXON SIGNED RANK TEST: z=15.636, P<0.001).
      Comparison of the baseline and post-definition medians (7 and 15, respectively)
      indicated that the post-definition estimate was approximately twice the baseline.
      Follow-up analyses indicated that this effect was consistent across all levels of
      competition examined and across type of sport (contact versus non-contact).
      CONCLUSION: Our results indicate that athletes' current understandings of
      concussions are not consistent with a currently accepted medical definition. We
      strongly recommend that clinicians and researchers preface requests for self
      reported concussion history with a definition. In addition, it is extremely
      important that researchers report the definition they used in published
      manuscripts of their work. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: Our study
      shows that unprompted reporting of concussion history produces results that are
      significantly different from those provided after a definition has been given,
      suggesting one possible mechanism to improve the reliability of self-reported
      concussion history across multiple individuals.

PMID- 24891817
TI  - Prevention of eating disorders in female athletes.
AB  - Eating disorders are serious mental diseases that frequently appear in female
      athletes. They are abnormal eating behaviors that can be diagnosed only by strict
      criteria. Disordered eating, although also characterized as abnormal eating
      behavior, does not include all the criteria for diagnosing eating disorders and
      is therefore a way to recognize the problem in its early stages. It is important
      to identify factors to avoid clinical progression in this high-risk population.
      Therefore, the purpose of this review is to discuss critical information for the
      prevention of eating disorders in female athletes. This review discusses the
      major correlates for the development of an eating disorder. We also discuss which
      athletes are possibly at highest risk for eating disorders, including those from
      lean sports and female adolescent athletes. There is an urgent need for the
      demystification of myths surrounding body weight and performance in sports. This
      review includes studies that tested different prevention programs' effectiveness,
      and the majority showed positive results. Educational programs are the best
      method for primary prevention of eating disorders. For secondary prevention,
      early identification is essential and should be performed by preparticipation
      exams, the recognition of dietary markers, and the use of validated self-report
      questionnaires or clinical interviews. In addition, more randomized clinical
      trials are needed with athletes from multiple sports in order for the most
      reliable recommendations to be made and for some sporting regulations to be
      changed. 

PMID- 24891818
TI  - Genetic aspects of athletic performance: the African runners phenomenon.
AB  - The current dominance of African runners in long-distance running is an
      intriguing phenomenon that highlights the close relationship between genetics and
      physical performance. Many factors in the interesting interaction between
      genotype and phenotype (eg, high cardiorespiratory fitness, higher hemoglobin
      concentration, good metabolic efficiency, muscle fiber composition, enzyme
      profile, diet, altitude training, and psychological aspects) have been proposed
      in the attempt to explain the extraordinary success of these runners. Increasing
      evidence shows that genetics may be a determining factor in physical and athletic
      performance. But, could this also be true for African long-distance runners?
      Based on this question, this brief review proposed the role of genetic factors
      (mitochondrial deoxyribonucleic acid, the Y chromosome, and the angiotensin
      converting enzyme and the alpha-actinin-3 genes) in the amazing athletic
      performance observed in African runners, especially the Kenyans and Ethiopians,
      despite their environmental constraints. 

PMID- 24891819
TI  - Tettigettalnajosei (Boulard, 1982) (Hemiptera: Cicadoidea): first record in
      Spain, with notes on the distribution, genetic variation and behaviour of the
      species.
AB  - The small cicada Tettigettalnajosei (Boulard, 1982) was until recently only known
      from southern Portugal and was considered endemic to this country. Fieldwork in
      2013 led to the first record of the species in Spain, expanding its known eastern
      range to Andalusia. The northern limits remain poorly defined but it appears that
      the distribution of Tettigettalnajosei is restricted to the south Atlantic
      coastline in the Iberian Peninsula, with the highest densities found in Algarve.
      Some notes on behaviour and genetic variation of Tettigettalnajosei are also
      given. 

PMID- 24891820
TI  - The Supertree Toolkit 2: a new and improved software package with a Graphical
      User Interface for supertree construction.
AB  - Building large supertrees involves the collection, storage, and processing of
      thousands of individual phylogenies to create large phylogenies with thousands to
      tens of thousands of taxa. Such large phylogenies are useful for
      macroevolutionary studies, comparative biology and in conservation and
      biodiversity. No easy to use and fully integrated software package currently
      exists to carry out this task. Here, we present a new Python-based software
      package that uses well defined XML schema to manage both data and metadata. It
      builds on previous versions by 1) including new processing steps, such as Safe
      Taxonomic Reduction, 2) using a user-friendly GUI that guides the user to
      complete at least the minimum information required and includes context-sensitive
      documentation, and 3) a revised storage format that integrates both tree- and
      meta-data into a single file. These data can then be manipulated according to a
      well-defined, but flexible, processing pipeline using either the GUI or a command
      line based tool. Processing steps include standardising names, deleting or
      replacing taxa, ensuring adequate taxonomic overlap, ensuring data independence,
      and safe taxonomic reduction. This software has been successfully used to store
      and process data consisting of over 1000 trees ready for analyses using standard
      supertree methods. This software makes large supertree creation a much easier
      task and provides far greater flexibility for further work. 

PMID- 24891821
TI  - Review of the genus Metopheltes Uchida, 1932 (Hymenoptera, Ichneumonidae) with
      description of a new species from Vietnam.
AB  - A new species of the genus Metopheltes Uchida (Hymenoptera: Ichneumonidae,
      Ctenopelmatinae), Metopheltesclypeoarmatus sp. n. is described from Vietnam.
      Metopheltespetiolaris Uchida, 1932 is recorded for the first time from the
      Russian Far East. The other previously described species are also illustrated and
      discussed. 

PMID- 24891822
TI  - J.G.C. Lehmann's 'Botanical Observations' of 1818 on Coldenia, Colsmannia,
      Cynoglossum, and Omphalodes (commented translation).
AB  - An annotated English translation of a German early 19th century text including
      Latin diagnoses is presented with a high-quality scan of the original publication
      and direct links to the cited pages with taxon and literature citations
      (including TL-2 entries). 

PMID- 24891823
TI  - Millipedes and centipedes in German greenhouses (Myriapoda: Diplopoda,
      Chilopoda).
AB  - A review is given of all the literature records of millipedes and centipedes that
      have been found in German greenhouses together with additional records for 29
      such sites. Species lists are given for 46 greenhouses investigated throughout
      Germany. Thirty-five diplopod and 18 chilopod species were found to occur in
      greenhouses, of which 15 (3 Chilopoda, 12 Diplopoda) are restricted to this type
      of habitat. First records for Germany include Anadenobolusmonilicornis (Porat,
      1876), Epinannolenecf.trinidadensis Chamberlin, 1918, Epinannolene sp.,
      Mesoiulusgridellii Strasser, 1934, Leptogoniulussorornus (Butler, 1876),
      Rhinotuspurpureus (Pocock, 1894), Cryptopsdoriae Pocock, 1891, Lamyctescoeculus
      (Brolemann, 1889) and Tygarrupjavanicus (Attems, 1907). The millipedes
      Oxidusgracilis (C. L. Koch, 1847) and Amphitomeusattemsi (Schubart, 1934) and the
      centipedes Lithobiusforficatus (Linnaeus, 1758) and Cryptopshortensis (Donovan,
      1810) are the species most frequently found in greenhouses. 

PMID- 24891824
TI  - Towards the conservation of parasitoid wasp species in Canada: Preliminary
      assessment of Microgastrinae (Hymenoptera: Braconidae).
AB  - This paper is the first to consider braconid parasitoid wasps in conservation
      efforts in Canada. Out of the 28 genera of the subfamily Microgastrinae
      (Hymenoptera: Braconidae) present in the country, 13 genera were studied and 16
      species were identified as potential candidates to be included in the Species
      Candidate Lists of COSEWIC (The Committee on the Status of Endangered Wildlife in
      Canada). For every selected species a brief summary of its broad geographical
      distribution is provided, with detailed and in many cases new information of its
      distribution and collecting dates in Canada, hosts (Lepidoptera) if known, and
      color pictures of all wasp species. A preliminary assessment is made using
      Prioritization Criteria developed by COSEWIC, and some general recommendations
      are made based in those analyses. 

PMID- 24891825
TI  - Recent noteworthy findings of fungus gnats from Finland and northwestern Russia
      (Diptera: Ditomyiidae, Keroplatidae, Bolitophilidae and Mycetophilidae).
AB  - New faunistic data on fungus gnats (Diptera: Sciaroidea excluding Sciaridae) from
      Finland and NW Russia (Karelia and Murmansk Region) are presented. A total of 64
      and 34 species are reported for the first time form Finland and Russian Karelia,
      respectively. Nine of the species are also new for the European fauna:
      Mycomyashewelli Vaisanen, 1984, Mycomyathula Vaisanen, 1984, Acnemiatrifida
      Zaitzev, 1982, Coelosiagracilis Johannsen, 1912, Orfeliakrivosheinae Zaitzev,
      1994, Mycetophilabiformis Maximova, 2002, Mycetophilamonstera Maximova, 2002,
      Mycetophilauschaica Subbotina & Maximova, 2011 and Trichontapalustris Maximova,
      2002. 

PMID- 24891826
TI  - Chromosome studies in the aquatic monocots of Myanmar: A brief review with
      additional records.
AB  - Myanmar (Burma) constitutes a significant component of the Indo-Myanmar
      biodiversity hotspot, with elements of the Indian, the Indochina, and the Sino
      Japanese floristic regions, yet thus far only a few reliable sources of the
      country's flora have been available. As a part of a contribution for the
      floristic inventory of Myanmar, since it is important in a floristic survey to
      obtain as much information as possible, in addition to previous two reports, here
      we present three more chromosome counts in the aquatic monocots of Myanmar:
      Limnocharisflava with 2n = 20, Sagittariatrifolia with 2n = 22 (Alismataceae),
      and Potamogetondistinctus * Potamogetonnodosus with 2n = 52 (Potamogetonaceae);
      the third one is new to science. A brief review of cytological researches in the
      floristic regions' 45 non-hybrid aquatic monocots plus well investigated two
      inter-specific hybrids that are recorded in Myanmar is given, indicating that the
      further works with a focus on species in Myanmar that has infra-specific
      chromosome variation in the floristic regions will address the precise
      evolutionary history of the aquatic flora of Myanmar. 

PMID- 24891827
TI  - Review of the genus Namadytes Hesse, 1969 (Insecta: Diptera: Mydidae:
      Syllegomydinae).
AB  - The Mydidae genus Namadytes Hesse, 1969 is reviewed. It is known from five
      species, primarily occurring in Namibia. The study of newly available material
      from both Namibia and South Africa deposited in several natural history
      collections results in the recognition of three species and new synonymy of two,
      i.e., Namadytespallidus Hesse, 1972 is a new junior synonym of
      Namadytesmaculiventris (Hesse, 1969) and Namadytesprozeskyi Hesse, 1969: 282 is a
      new junior synonym of Namadytesvansoni Hesse, 1969: 280. All three species are re
      described and comments on sexual dimorphism and intraspecific variation are made,
      a dichotomous key for their identification is presented, and illustrations and
      photographs are provided to support the descriptions and facilitate future
      identification. Distribution, occurrence in biodiversity hotspots sensu
      Conservation International, and seasonal incidence with associated weather and
      climatic data are discussed for all species. A morphological structure ventral to
      the halter and posterior to the metathoracic spiracle, the infra-halter sclerite,
      is here newly termed. 

PMID- 24891828
TI  - Campylomorphushomalisinus (Elateridae): a new species for Lombardy (Italy), with
      notes on its ecology, distribution and biogeography.
AB  - Campylomorphushomalisinus has been found on Mt. Lesima (Northern Apennines) and
      it is the first record for the Lombardy region. Campylomorphushomalisinus is a
      rare orophilous species: it has a discontinuous chorology that may have been
      caused by glaciers dynamics during the Pleistocene era. Little is known about the
      ecology of the species. This record and the expert-based investigation we
      performed determined that Campylomorphushomalisinus inhabits shrublands and
      grasslands, but may also occur in the forests. This survey includes the only
      record of Campylomorphushomalisinus foraging on flowers, a behavior that is not
      rare in the family Elateridae. We hypothesize that adults integrate their diet
      with flower resources according to a generalist strategy. 

PMID- 24891830
TI  - Notes on the biology, distribution, biosecurity status and history in New Zealand
      of Macrotrachelianigronitens (Stal, 1860) (Heteroptera: Anthocoridae).
AB  - Macrotrachelianigronitens (Stal, 1860) (Heteroptera: Anthocoridae) is permanently
      present in the wild in Auckland (AK), New Zealand. It should therefore be added
      to the New Zealand Organisms Register (NZOR). It is a specialised predator of
      thrips inside leaf-roll galls. It has been present in New Zealand since at least
      the 1980s. Aspects of its biology, distribution, biosecurity status and history
      in New Zealand are discussed. The first detailed specimen records from New
      Zealand are provided, and a biological association is noted for the first time
      with Teuchothripsdisjunctus on Callistemon, probably its main association in New
      Zealand, where only two species of thrips cause leaf-roll galls. It has not been
      found associated with other thrips in New Zealand. Macrotrachelianigronitens is
      not known to be present in Australia, but the poorly known Anthocorisaustropiceus
      Gross, 1954 has been reported, in an easily overlooked publication, to be
      associated with Teuchothripsdisjunctus on Callistemon in Canberra. This led to an
      early tentative identification, by the author, of New Zealand material of
      Macrotrachelianigronitens as Anthocorisaustropiceus, in collections. This likely
      misidentification can now be discounted, but further research in Australia is
      required to determine the true identity of both Anthocorisaustropiceus, and
      whatever species of anthocorid was found in Canberra. 

PMID- 24891829
TI  - Dispatch from the field: ecology of ground-web-building spiders with description
      of a new species (Araneae, Symphytognathidae).
AB  - Crassignathadanaugirangensis sp. n. (Araneae: Symphytognathidae) was discovered
      during a tropical ecology field course held at the Danau Girang Field Centre in
      Sabah, Malaysia. A taxonomic description and accompanying ecological study were
      completed as course activities. To assess the ecology of this species, which
      belongs to the ground-web-building spider community, three habitat types were
      surveyed: riparian forest, recently inundated riverine forest, and oil palm
      plantation. Crassignathadanaugirangensis sp. n. is the most abundant ground-web
      building spider species in riparian forest; it is rare or absent from the
      recently inundated forest and was not found in a nearby oil palm plantation. The
      availability of this taxonomic description may help facilitate the accumulation
      of data about this species and the role of inundated riverine forest in shaping
      invertebrate communities. 

PMID- 24891831
TI  - Edaphic and light conditions of sympatric plant morphotypes in western Amazonia.
AB  - Here I present a dataset of edaphic and light conditions associated with the
      occurrence of sympatric morphotypes of Geonomamacrostachys (Arecaceae/Palmae), a
      candidate case study from Amazonia hypothesized to have evolved under ecological
      speciation. Transects were established in three lowland rainforests in Peru, and
      the abundance of each local morphotype of this species was recorded in a total
      area of 4.95 hectares. Composite soil samples and hemispherical photographs were
      taken along the transects were the species occurred to obtain information on soil
      nutrients, soil texture, and indirect measurements of light availability. The raw
      and summary tables disclose the characteristics of each study site and habitats
      within them, which could be useful to soil scientists, ecologists, and
      conservationists engaged in similar research activities or meta-analyses in
      Amazonia. 

PMID- 24891832
TI  - The Encyclopedia of Life v2: Providing Global Access to Knowledge About Life on
      Earth.
AB  - The Encyclopedia of Life (EOL, http://eol.org) aims to provide unprecedented
      global access to a broad range of information about life on Earth. It currently
      contains 3.5 million distinct pages for taxa and provides content for 1.3 million
      of those pages. The content is primarily contributed by EOL content partners
      (providers) that have a more limited geographic, taxonomic or topical scope. EOL
      aggregates these data and automatically integrates them based on associated
      scientific names and other classification information. EOL also provides
      interfaces for curation and direct content addition. All materials in EOL are
      either in the public domain or licensed under a Creative Commons license. In
      addition to the web interface, EOL is also accessible through an Application
      Programming Interface. In this paper, we review recent developments added for
      Version 2 of the web site and subsequent releases through Version 2.2, which have
      made EOL more engaging, personal, accessible and internationalizable. We outline
      the core features and technical architecture of the system. We summarize
      milestones achieved so far by EOL to present results of the current system
      implementation and establish benchmarks upon which to judge future improvements.
      We have shown that it is possible to successfully integrate large amounts of
      descriptive biodiversity data from diverse sources into a robust, standards
      based, dynamic, and scalable infrastructure. Increasing global participation and
      the emergence of EOL-powered applications demonstrate that EOL is becoming a
      significant resource for anyone interested in biological diversity. 

PMID- 24891833
TI  - The influence of landscape heterogeneity - ground beetles (coleoptera: carabidae)
      in fthiotida, central Greece.
AB  - Pitfall traps were used to sample Carabidae in agricultural land of the
      Spercheios valley, Fthiotida, Central Greece. Four pairs of cultivated fields
      were sampled. One field of each pair was located in a heterogeneous area and the
      other in a more homogeneous area. Heterogeneous areas were composed of small
      fields. They had high percentages of non-cropped habitats and a high diversity of
      land use types. Homogeneous areas were composed of larger fields. They had lower
      percentages of non-cropped habitats and a lower diversity of land use types. One
      pair of fields had been planted with cotton, one with maize, one with olives and
      one with wheat. Altogether 28 carabid species were recorded. This paper describes
      the study areas, the sampling methods used and presents the data collected during
      the study. Neither heterogeneous nor homogeneous areas had consistently higher
      abundance levels, activity density levels, species richness levels or diversity
      levels. However, significant differences were seen in some of the comparisons
      between heterogeneous and homogeneous areas. 

PMID- 24891834
TI  - Checklist of fishes from madagascar reef, campeche bank, mexico.
AB  - This study presents the first list of fish species from Madagascar Reef, Campeche
      Bank, Gulf of Mexico. Field surveys and literature review identified 54 species
      belonging to 8 orders, 30 families and 43 genera, comprising both conspicuous and
      cryptic fishes. Species richness was lower at this reef site compared to reefs in
      the Mexican Caribbean, Veracruz or Tuxpan, but was similar to other reefs in the
      same region. Species composition was a mixture of species present in all the reef
      systems of the Mexican Atlantic. Hypoplectrusecosur was recorded here for the
      first time in the Gulf of Mexico, Mycteropercamicrolepis, Equetuslanceolatus and
      Chaetodipterusfaber were new records for the reefs of the Campeche Bank,
      Elacatinusxanthiprora was recorded for the second time in Mexico and expanded its
      known distribution westwards from Alacranes Reef and Sanopusreticulatus, endemic
      of the Yucatan state, was recorded here for the first time on a reef. 

PMID- 24891835
TI  - Why is the lawn buzzing?
AB  - Graminoids, including grasses, are frequently described in the botanical
      literature as being wind-pollinated. This paper offers visual evidence for insect
      pollination of a grass. Three of the bees involved were found to have 100% grass
      pollen in their pollen sacs. In reviewing the literature for this paper, it was
      evident that those working with bees are well aware that these insects often
      pollinate graminoids. It is not clear why this information has not been
      incorporated into the botanical literature. 

PMID- 24891836
TI  - A Model Study toward the Concise Synthesis of Bromotyrosine Derived
      Spiroisoxazoline Natural Products and Analogous Core Structures.
AB  - A model study of the first non-aromatic ring based approach toward alpha
      hydroxyspiroisoxazolines resembling the bromotyrosine derived natural product and
      analogous spiroisoxazoline core structures were implemented. The desired
      molecular architecture was achieved through the multifunctionalization of a key
      1,3-diketo spiroisoxazoline. Our strategy could serve as an efficient alternative
      of previously developed approaches that utilize an aromatic ring oxidation as the
      essential step to synthesize this class of natural products.

PMID- 24891837
TI  - Cost analysis of the stroke volume variation guided perioperative hemodynamic
      optimization - an economic evaluation of the SVVOPT trial results.
AB  - BACKGROUND: Perioperative goal directed therapy (GDT) can substantially improve
      the outcomes of high risk surgical patients as shown by many clinical studies.
      However, the approach needs initial investment and can increase the already very
      high staff workload. These economic imperatives may be at least partly
      responsible for weak adherence to the GDT concept. A few models are available for
      the evaluation of GDT cost-effectiveness, but studies of real economic data based
      on a recent clinical trial are lacking. In order to address this we have
      performed a retrospective analysis of the data from the "Intraoperative fluid
      optimization using stroke volume variation in high risk surgical patients" trial
      (ISRCTN95085011). METHODS: The health-care payers perspective was used in order
      to evaluate the perioperative hemodynamic optimization costs. Hospital invoices
      from all patients included in the trial were extracted. A direct comparison
      between the study (GDT, N = 60) and control (N = 60) groups was performed. A cost
      tree was constructed and major cost drivers evaluated. RESULTS: The trial showed
      a significant improvement in clinical outcomes for GDT treated patients. The mean
      cost per patient were lower in the GDT group 2877 +/- 2336? vs. 3371 +/- 3238? in
      controls, but without reaching a statistical significance (p = 0.596). The mean
      cost of all items except for intraoperative monitoring and infusions were lower
      for GDT than control but due to the high variability they all failed to reach
      statistical significance. Those costs associated with clinical care (68 +/- 177?
      vs. 212 +/- 593?; p = 0.023) and ward stay costs (213 +/- 108? vs. 349 +/- 467?;
      p = 0.082) were the most important differences in favour of the GDT group.
      CONCLUSIONS: Intraoperative fluid optimization with the use of stroke volume
      variation and Vigileo/FloTrac system showed not only a substantial improvement of
      morbidity, but was associated with an economic benefit. The cost-savings observed
      in the overall costs of postoperative care trend to offset the investment needed
      to run the GDT strategy and intraoperative monitoring. TRIAL REGISTRATION:
      ISRCTN95085011.

PMID- 24891838
TI  - Retrospective derivation and validation of a search algorithm to identify
      extubation failure in the intensive care unit.
AB  - BACKGROUND: Development and validation of automated electronic medical record
      (EMR) search strategies is important in identifying extubation failure in the
      intensive care unit (ICU). We developed and validated an automated search
      algorithm (strategy) for extubation failure in critically ill patients. METHODS:
      The EMR search algorithm was created through sequential steps with keywords
      applied to an institutional EMR database. The search strategy was derived
      retrospectively through secondary analysis of a 100-patient subset from the 978
      patient cohort admitted to a neurological ICU from January 1, 2002, through
      December 31, 2011(derivation subset). It was, then, validated against an
      additional 100-patient subset (validation subset). Sensitivity, specificity,
      negative and positive predictive values of the automated search algorithm were
      compared with a manual medical record review (the reference standard) for data
      extraction of extubation failure. RESULTS: In the derivation subset of 100 random
      patients, the initial automated electronic search strategy achieved a sensitivity
      of 85% (95% CI, 56%-97%) and a specificity of 95% (95% CI, 87%-98%). With
      refinements in the search algorithm, the final sensitivity was 93% (95% CI, 64%
      99%) and specificity increased to 100% (95% CI, 95%-100%) in this subset. In
      validation of the algorithm through a separate 100 random patient subset, the
      reported sensitivity and specificity were 94% (95% CI, 69%-99%) and 98% (95% CI,
      92%-99%) respectively. CONCLUSIONS: Use of electronic search algorithms allows
      for correct extraction of extubation failure in the ICU, with high degrees of
      sensitivity and specificity. Such search algorithms are a reliable alternative to
      manual chart review for identification of extubation failure.

PMID- 24891840
TI  - The effect of a continuing medical education program on Venous thromboembolism
      prophylaxis utilization and mortality in a tertiary-care hospital.
AB  - BACKGROUND: Venous thromboembolism (VTE) prophylaxis is underutilized for
      hospitalized patients. The primary objective of this study was to assess the
      impact of a continuing medical education (CME) program on thromboprophylaxis and
      VTE-associated mortality in a tertiary-care hospital. METHODS: This was a
      retrospective study of all patients admitted to a tertiary-care hospital from
      01/07/2009 to 30/06/2010 (after a CME program that aimed at improving VTE
      prophylaxis) and had confirmed VTE during stay. VTE prophylaxis utilization and
      associated mortality were assessed in them and compared to those of a similar
      cohort of patients hospitalized in the previous 12 months. RESULTS: There were
      147 confirmed VTE cases in the study period (surgical: 26.5% and medical: 73.5%).
      Most (63.9%) VTE patients received prophylaxis after the CME program compared
      with 36.5% in the previous 12 months (relative risk 1.73; 95% confidence
      interval, 1.38-2.18; P < 0.001). More surgical (82.1%) than medical (57.4%)
      patients received prophylaxis (P < 0.01). VTE-associated mortality rate was 10.9%
      with a significant decrease after the CME program (relative risk, 0.52; 95%
      confidence interval, 0.30-0.90). This mortality was lower for those who received
      VTE prophylaxis compared to those who didn't (4.3% and 22.6%, respectively; P <
      0.01). Additionally, VTE-associated deaths represented 1.1% of total hospital
      mortality compared to 1.9% in the 12 months before CME program (relative risk,
      0.58; 95% confidence interval, 0.32-1.04; P = 0.07). CONCLUSIONS: A CME
      educational program to improve VTE prophylaxis in a tertiary-care hospital was
      associated with improvement in VTE prophylaxis utilization and VTE-associated
      mortality. Such programs are highly recommended.

PMID- 24891842
TI  - Comparison of Algorithms for Haptic Interaction With Isosurfaces Extracted From
      Volumetric Datasets.
AB  - Combinations of graphics and haptics libraries are used in medical simulations
      for simultaneous visualization and tactile interaction with complex 3D anatomy
      models. The minimum frame rate of 1 kHz for haptics rendering makes it a
      nontrivial problem when dealing with complex and highly detailed polygonal
      models. Multiple haptics algorithms based on polygonal mesh rendering, volume
      haptics, and intermediate representation are evaluated in terms of their
      servoloop rendering time, client thread rendering time, and quality of force
      feedback. Algorithms include OpenHaptics' Feedback Buffer and Depth Buffer,
      GodObject and Ruspini renderers in h3d, chai3d implementation in h3d,
      ScalarSurfaceFriction mode in Volume Haptics ToolKit (vhtk), and the authors'
      intermediate representation algorithm based on volumetric data. The latter, in
      combination with surface graphics visualization, is found to deliver the best
      rendering time, to detect all collisions and to provide correct haptic feedback
      where other algorithms fail.

PMID- 24891839
TI  - Pepsin-pancreatin protein hydrolysates from extruded amaranth inhibit markers of
      atherosclerosis in LPS-induced THP-1 macrophages-like human cells by reducing
      expression of proteins in LOX-1 signaling pathway.
AB  - BACKGROUND: Atherosclerosis is considered a progressive disease that affects
      arteries that bring blood to the heart, to the brain and to the lower end. It
      derives from endothelial dysfunction and inflammation, which play an important
      role in the thrombotic complications of atherosclerosis. Cardiovascular disease
      is the leading cause of death around the world and one factor that can contribute
      to its progression and prevention is diet. Our previous study found that amaranth
      hydrolysates inhibited LPS-induced inflammation in human and mouse macrophages by
      preventing activation of NF-kappaB signaling. Furthermore, extrusion improved the
      anti-inflammatory effect of amaranth protein hydrolysates in both cell lines,
      probably attributed to the production of bioactive peptides during processing.
      Therefore, the objective of this study was to compare the anti-atherosclerotic
      potential of pepsin-pancreatin hydrolysates from unprocessed and extruded
      amaranth in THP-1 lipopolysaccharide-induced human macrophages and suggest the
      mechanism of action. RESULTS: Unprocessed amaranth hydrolysate (UAH) and extruded
      amaranth hydrolysate (EAH) showed a significant reduction in the expression of
      interleukin-4 (IL-4) (69% and 100%, respectively), interleukin-6 (IL-6) (64% and
      52%, respectively), interleukin-22 (IL-22) (55% and 70%, respectively). Likewise,
      UAH and EAH showed a reduction in the expression of monocyte-chemo attractant
      protein-1 (MCP-1) (35% and 42%, respectively), transferrin receptor-1 (TfR-1)
      (48% and 61%, respectively), granulocyte-macrophage colony-stimulating factor (GM
      CSF) (59% and 63%, respectively), and tumor necrosis factor-alpha (TNF-alpha)
      (60% and 63%, respectively). Also, EAH reduced the expression of lectin-like
      oxidized low-density lipoprotein receptor-1 (LOX-1) (27%), intracellular adhesion
      molecule-1 (ICAM-1) (28%) and matrix metalloproteinase-9 (MMP-9) (19%), important
      molecular markers in the atherosclerosis pathway. EAH, led to a reduction of 58,
      52 and 79% for LOX-1, ICAM-1 and MMP-9, respectively, by confocal microscopy.
      CONCLUSIONS: Extruded amaranth hydrolysate showed potential anti-atherosclerotic
      effect in LPS-induced THP-1 human macrophage-like cells by reducing the
      expression of proteins associated with LOX-1 signaling pathway.

PMID- 24891841
TI  - Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the
      presence of clopidogrel.
AB  - BACKGROUND: Platelet inhibitors are commonly used to reduce the risk of
      atherothrombotic events. The aim of this study was to determine the impact of
      platelet inhibitors, specifically clopidogrel and aspirin, on clot kinetics,
      strength, and/or structure during the use of thrombin based gelatin matrices and
      fibrin sealants. METHODS: Blood was collected and heparinized from donors on
      clopidogrel (and aspirin) and age matched control donors. Blood component
      analysis, whole blood platelet aggregometry, and activated clotting time (ACT)
      were used to monitor compliance to therapy and identify any differences between
      donor groups. Clot kinetics and strength were analyzed using thrombelastography
      (TEG). Field Emission Scanning Electron Microscopy (FESEM) was used to analyze
      clot structure. RESULTS: Blood component profiles were similar for both donor
      groups. Aggregometry indicated that aggregation response to adenosine diphosphate
      (ADP) for clopidogrel donors was 12% of that for the controls (p = 0.0021), an
      expected result of clopidogrel induced platelet inhibition. However, blood from
      both donor groups had an elevated thrombin induced aggregation response.
      Heparinization of donor blood resulted in similarly elevated ACTs for both donor
      groups. TEG results indicated similar clot kinetics and strength between
      clopidogrel and control donor groups for blood alone and when clotting was
      induced using thrombin based gelatin matrices and fibrin sealants. FESEM images
      supported TEG findings in that similar morphologies were observed in ex vivo
      formed clots from both donor groups when thrombin based gelatin matrices and
      fibrin sealants were used. CONCLUSION: These results suggest that platelet
      inhibitors do not negatively impact clot kinetics, strength, and structure when
      clotting is initiated with thrombin based gelatin matrices and fibrin sealants.

PMID- 24891843
TI  - Urban ecology in a developing world: why advanced socioecological theory needs
      Africa.
AB  - Socioecological theory, developed through the study of urban environments, has
      recently led to a proliferation of research focusing on comparative analyses of
      cities. This research emphasis has been concentrated in the more developed
      countries of the Northern Hemisphere (often referred to as the "Global North"),
      yet urbanization is now occurring mostly in the developing world, with the
      fastest rates of growth in sub-Saharan Africa. Countries like South Africa are
      experiencing a variety of land-cover changes that may challenge current
      assumptions about the differences between urban and rural environments and about
      the connectivity of these dynamic socioecological systems. Furthermore, questions
      concerning ecosystem services, landscape preferences, and conservation - when
      analyzed through rural livelihood frameworks - may provide insights into the
      social and ecological resilience of human settlements. Increasing research on
      urban development processes occurring in Africa, and on patterns of kinship and
      migration in the less developed countries of the "Global South", will advance a
      more comprehensive worldview of how future urbanization will influence the
      progress of sustainable societies.

PMID- 24891845
TI  - Performance of Solid Oxide Fuel Cell With La and Cr Co-doped SrTiO3 as Anode.
AB  - The La0.3Sr0.55Ti0.9Cr0.1O3-delta (LSTC10) anode material was synthesized by
      citric acid-nitrate process. The yttria-stabilized zirconia (YSZ) electrolyte
      supported cell was fabricated by screen printing method using LSTC10 as anode and
      (La0.75Sr0.25)0.95MnO3-delta (LSM) as cathode. The electrochemical performance of
      cell was tested by using dry hydrogen as fuel and air as oxidant in the
      temperature range of 800-900  degrees C. At 900  degrees C, the open circuit
      voltage (OCV) and the maximum power density of cell are 1.08 V and 13.0 mW.cm-2,
      respectively. The microstructures of cell after performance testing were
      investigated by scanning electron microscope (SEM). The results show that the
      anode and cathode films are porous and closely attached to the YSZ electrolyte.
      LSTC10 is believed to be a kind of potential solid oxide fuel cell (SOFC) anode
      material.

PMID- 24891846
TI  - The Use of Generalized Laguerre Polynomials in Spectral Methods for Solving
      Fractional Delay Differential Equations.
AB  - In this paper, an efficient numerical method for solving the fractional delay
      differential equations (FDDEs) is considered. The fractional derivative is
      described in the Caputo sense. The proposed method is based on the derived
      approximate formula of the Laguerre polynomials. The properties of Laguerre
      polynomials are utilized to reduce FDDEs to a linear or nonlinear system of
      algebraic equations. Special attention is given to study the error and the
      convergence analysis of the proposed method. Several numerical examples are
      provided to confirm that the proposed method is in excellent agreement with the
      exact solution.

PMID- 24891847
TI  - Model Predictive Control of Fractional Order Systems.
AB  - This paper provides the model predictive control (MPC) of fractional order
      systems. The direct method will be used as internal model to predict the future
      dynamic behavior of the process, which is used to achieve the control law. This
      method is based on the Grunwald-Letnikov's definition that consists of replacing
      the noninteger derivation operator of the adopted system representation by a
      discrete approximation. The performances and the efficiency of this approach are
      illustrated with practical results on a thermal system and compared to the MPC
      based on the integer ARX model.

PMID- 24891844
TI  - Clinical features of childhood granulomatosis with polyangiitis (wegener's
      granulomatosis).
AB  - BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly known as Wegener's
      granulomatosis (WG), belongs to the group of ANCA-associated necrotizing
      vasculitides. This study describes the clinical picture of the disease in a large
      cohort of GPA paediatric patients. Children with age at diagnosis <= 18 years,
      fulfilling the EULAR/PRINTO/PRES GPA/WG classification criteria were extracted
      from the PRINTO vasculitis database. The clinical signs/symptoms and laboratory
      features were analysed before or at the time of diagnosis and at least 3 months
      thereafter and compared with other paediatric and adult case series (>50
      patients) derived from the literature. FINDINGS: The 56 children with GPA/WG were
      predominantly females (68%) and Caucasians (82%) with a median age at disease
      onset of 11.7 years, and a median delay in diagnosis of 4.2 months. The most
      frequent organ systems involved before/at the time of diagnosis were ears, nose,
      throat (91%), constitutional (malaise, fever, weight loss) (89%), respiratory
      (79%), mucosa and skin (64%), musculoskeletal (59%), and eye (35%), 67% were ANCA
      PR3 positive, while haematuria/proteinuria was present in > 50% of the children.
      In adult series, the frequency of female involvement ranged from 29% to 50% with
      lower frequencies of constitutional (fever, weight loss), ears, nose, throat
      (oral/nasal ulceration, otitis/aural discharge), respiratory
      (tracheal/endobronchial stenosis/obstruction), laboratory involvement and higher
      frequency of conductive hearing loss than in this paediatric series. CONCLUSIONS:
      Paediatric patients compared to adults with GPA/WG have similar pattern of
      clinical manifestations but different frequencies of organ involvement.

PMID- 24891848
TI  - High-Speed GPU-Based Fully Three-Dimensional Diffuse Optical Tomographic System.
AB  - We have developed a graphics processor unit (GPU-) based high-speed fully 3D
      system for diffuse optical tomography (DOT). The reduction in execution time of
      3D DOT algorithm, a severely ill-posed problem, is made possible through the use
      of (1) an algorithmic improvement that uses Broyden approach for updating the
      Jacobian matrix and thereby updating the parameter matrix and (2) the multinode
      multithreaded GPU and CUDA (Compute Unified Device Architecture) software
      architecture. Two different GPU implementations of DOT programs are developed in
      this study: (1) conventional C language program augmented by GPU CUDA and CULA
      routines (C GPU), (2) MATLAB program supported by MATLAB parallel computing
      toolkit for GPU (MATLAB GPU). The computation time of the algorithm on host CPU
      and the GPU system is presented for C and Matlab implementations. The forward
      computation uses finite element method (FEM) and the problem domain is
      discretized into 14610, 30823, and 66514 tetrahedral elements. The reconstruction
      time, so achieved for one iteration of the DOT reconstruction for 14610 elements,
      is 0.52 seconds for a C based GPU program for 2-plane measurements. The
      corresponding MATLAB based GPU program took 0.86 seconds. The maximum number of
      reconstructed frames so achieved is 2 frames per second. 

PMID- 24891849
TI  - Etiopathogenesis of Sheehan's Syndrome: Roles of Coagulation Factors and TNF
      Alpha.
AB  - Sheehan's Syndrome (SS) is defined as pituitary hormone deficiency due to
      ischemic infarction of the pituitary gland as a result of massive postpartum
      uterine hemorrhage. Herein, we aimed to investigate the roles of Factor II
      (G20210A), Factor V (G1691A), MTHFR (C677T and A1298C), PAI-1 4G/5G, and TNF-
      alpha (-308  G > A) gene polymorphisms in the etiopathogenesis of SS. Venous
      blood samples were obtained from 53 cases with SS and 43 healthy women. Standard
      methods were used to extract the genomic DNAs. Factor II (G20210A), Factor V
      (G1691A), and MTHFR (C677T and A1298C) polymorphisms were identified by real-time
      PCR. PAI-1 4G/5G and TNF- alpha (-308  G > A) gene polymorphisms were detected
      with polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP) methods. According to statistical analysis, none of the polymorphisms were
      found to be significantly higher in the SS group compared to the control group.
      Hence, we suggest that genetic factors other than Factor II, Factor V, MTHFR, PAI
      1, and TNF- alpha gene polymorphisms should be researched in the etiopathogenesis
      of SS. 

PMID- 24891851
TI  - In vitro evaluation of some types of ferrimagnetic glass ceramics.
AB  - The present study aimed at studying the acceleration of the bioactive layer on
      the surface of ferrimagnetic glass ceramic with a basic composition 40Fe2O3
      15P2O5-20SiO2-5TiO2 through the addition of 20% of different types of metal
      oxides like MgO or CaO or MnO or CuO or ZnO or CeO2. SEM, EDAX, and ICP were
      applied to present the results of the study. SEM and EDAX measurements indicated
      the presence of apatite layer formed on the surface of the prepared glass
      ceramics after immersion in SBF within 7 to 30 days. The investigation of the
      results clarified that the addition of CaO or ZnO accelerated the formation of
      apatite on the surfaces of the samples in the simulated body fluid faster than
      other metal oxides. Inductive coupled plasma (ICP) analysis shows the evolution
      of ion extraction by the simulated body fluid solution (SBF) with time in
      relation to the elemental composition. 

PMID- 24891850
TI  - Oral cancer and oral potentially malignant disorders.

PMID- 24891852
TI  - The clinical characteristics of lower lumbar osteoporotic compression fractures
      treated by percutaneous vertebroplasty : a comparative analysis of 120 cases.
AB  - OBJECTIVE: The purpose of this study is to provide accurate understanding of
      clinical presentations and surgical outcomes as well as to identify the unique
      characteristics of lower lumbar osteoporotic compression fracture (OCF). METHODS:
      Clinical data were collected from 120 patients who had L3, L4 or L5 percutaneous
      vertebroplasty (PVP) performed from 2008 to 2012 at the single institute. L4 or
      L5 PVP patients were classified into group 1 and group 2 was for L3 PVP patients.
      Medical records were retrospectively investigated at 1 month after PVP. Long term
      follow-up results were obtained at a median value of 22 months after PVP.
      RESULTS: 75% of the patients in group 1 were not associated with traumatic
      events, 71% presenting with leg radiating symptoms and 46% requiring an
      additional decompressive surgery, more often than those in group 2. These
      differences are statistically significant (p<0.05). The short term medical record
      review demonstrated that only 73% of patients in group 1 were ameliorated with
      regard to back motion pain, whereas those in group 2 reported 87.7% rates of
      amelioration in identical category (p<0.05). The long term follow up confirmed a
      significantly worse outcome in group 1, with only 55.7% of patients reporting
      amelioration in their pain or functional status, but 71.7% rate of amelioration
      in group 2. CONCLUSION: The OCFs at the L4 or L5 level have different clinical
      characteristics from those at upper levels of the lumbar spine.

PMID- 24891853
TI  - Recurrence Rate after Herniotomy only versus Discectomy in Lumbar Disc
      Herniation.
AB  - OBJECTIVE: Lumbar disc herniation (LDH) recurrence necessitating reoperation can
      pose problems following spinal surgery, with an overall reported incidence of
      approximately (3-13%). The purpose of this study is to identify the rate of
      recurrent disc herniation, to discuss the radiologic indications for herniotomy
      and to analyze clinical outcomes compared with conventional discectomy. METHODS:
      This study is a retrospective case control study. The authors retrospectively
      reviewed 114 patients who underwent herniotomy & conventional discectomy by a
      single surgeon for single-level LDH between June 2009 and May 2012. Herniotomy
      group was 57 patients and conventional discectomy group was 57 patients that were
      selected from 631 patients using stratified randomization. Evaluation for LDH
      recurrence included detailed medical chart and radiologic review and telephone
      interview. Postoperative VAS and the Korean version of ODI were examined one week
      after surgery. Clinical outcome was investigated according to Odom's criteria
      from three months to three years. RESULTS: Of the 114 patients for whom the
      authors were able to definitively assess symptomatic recurrence status, four
      patients (7%) experienced LDH recurrence following single-level herniotomy and
      three patients (5.2%) conventional discectomy. There were no differences in the
      VAS and Korean version of ODI between herniotomy group and conventional
      discectomy group. The herniotomy group had better results than the conventional
      discectomy group in clinical outcome from three months to three years, but the
      difference was not significant. CONCLUSION: There were no significant differences
      in clinical outcome between herniotomy and conventional discectomy. Recurrence
      rates following herniotomy for LDH compare favorably with those in patients who
      have undergone conventional discectomy, lending further support for its
      effectiveness in treating herniotomy.

PMID- 24891854
TI  - Slip Reduction Rate between Minimal Invasive and Conventional Unilateral
      Transforaminal Interbody Fusion in Patients with Low-Grade Isthmic
      Spondylolisthesis.
AB  - OBJECTIVE: To compare the slip reduction rate and clinical outcomes between
      unilateral conventional transforaminal lumbar interbody fusion (conventional
      TLIF) and unilateral minimal invasive TLIF (minimal TLIF) with pedicle screw
      fixation for treatment of one level low-grade symptomatic isthmic
      spondylolisthesis. METHODS: Between February 2008 and April 2012, 25 patients
      with low-grade isthmic spondylolisthesis underwent conventional TLIF (12
      patients) and minimal TLIF (13 patients) in single university hospital by a
      single surgeon. Lateral radiographs of lumbar spine were taken 12 months after
      surgery to analyze the degree of slip reduction and the clinical outcome. All
      measurements were performed by a single observer. RESULTS: The demographic data
      between conventional TLIF and minimal TLIF were not different. Slip percentage
      was reduced from 15.00% to 8.33% in conventional TLIF, and from 14.15% to 9.62%
      in minimal TLIF. In both groups, slip percentage was significantly improved
      postoperatively (p=0.002), but no significant intergroup differences of slip
      percentage in preoperative and postoperative were found. The reduction rate also
      not different between conventional TLIF (45.41+/-28.80%) and minimal TLIF
      (32.91+/-32.12%, p=0.318). CONCLUSION: Conventional TLIF and minimal TLIF with
      pedicle screw fixation showed good slip reduction in patients with one level low
      grade symptomatic isthmic spondylolisthesis. The slip percentage and reduction
      rate were similar in the conventional TLIF and minimal TLIF.

PMID- 24891855
TI  - Is the Cross-sectional Area after Unilateral Open Door Laminoplasty Wider than
      that after Midline Splitting Laminoplasty ? : Mathematical Approach.
AB  - OBJECTIVE: The aim of this study was to compare geometrically cross-sectional
      areas of two different laminoplasty techniques in same opening size. Some
      investigators have studied the expanded areas of the two different techniques
      using imaging study. Although it is unclear that postoperative spinal canal is
      correlated with the surgical outcome we just focused on mathematical and
      geometrical correlation of the expandable area with surgical opening size in
      different laminoplasty techniques. METHODS: To predict the expandable area by a
      midline splitting technique and a unilateral open door technique, we placed an
      imaginary isosceles triangle in the spinal canal and drew graphs for the equation
      of the expandable areas in same opening size using the Pythagorean theorem and
      mathematical program. To substitute the constant figures of mathematical formula
      we estimated the normal cervical spine CT scans of 50 Korean adults. RESULTS: We
      subtracted the imaginary triangle from the spinal canal and were left with the
      remaining area of the spinal canal that was not changed before and after surgery.
      In same opening size the expandable area by the midline splitting technique was
      same but slightly wider than the unilateral open door technique, irrespective of
      the triangular shape. For a normal isosceles triangle the results were the same.
      CONCLUSION: Using mathematical proof, the expandable area after the midline
      splitting technique was same but slightly larger than that after the unilateral
      open door technique, irrespective of the size of the lamina opening.

PMID- 24891856
TI  - Histopathological findings of hemorrhagic ganglion cyst causing acute radicular
      pain: a case report.
AB  - Although juxtafacet cysts of the lumbar spine are being reported with increasing
      frequency, hemorrhage from a ganglion cyst is rare, and the pathophysiologic
      mechanism of the hemorrhage from the cyst is still unclear. A 75-year-old male
      presented with sudden radicular leg pain caused by hemorrhage from the ganglion
      cyst. Computed tomography revealed bony erosion of vertebral body and multiple
      punched-out lesions on facets. Magnetic resonance imaging showed the neural
      structure was compressed by a sharply delineating mass. Capsule and old hematoma
      with elastic consistency that extended to the epidural space were removed through
      a paramedian transforaminal approach, which led to the resolution of the
      patient's symptoms. Histopathologically, chronic inflammation with
      neovascularization and myxoid degeneration were present in the capsule. Alcian
      blue staining demonstrated the mixture of mucin and hematoma. The probable
      pathogenesis of hemorrhage from the cyst was discussed from the unique
      histopathological findings of surgical specimen. 

PMID- 24891857
TI  - Ventrally located cervical dumbbell ganglioneuroma producing spinal cord
      compression.
AB  - Ganglioneuroma is an uncommon benign tumor and arise from neural crest cells or
      sympathetic and peripheral nerves. A 13-year-old boy was referred to our
      institute and presented with three-day history of right upper extremity weakness
      associated with neck pain for nearly one month. Magnetic resonance imaging showed
      right side dumbbell shaped extramedullary lesion at the C2-3 level extending
      outside through neural foramen. Paraspinal and posterior neck mass, cafe au lait
      spot was identified. We performed surgical decompression of the spinal cord by
      resection of intradural portion mass. Histopathological diagnosis was
      ganglioneuroma. 

PMID- 24891858
TI  - Tapia syndrome after cervical spine surgery.
AB  - Tapia syndrome is a rare entity characterized by unilateral paralysis of the
      tongue and vocal cord caused by X(th) and XII(th) cranial nerve lesions. However,
      there has been no report of Tapia syndrome immediately following spine surgery. A
      47-year-old man underwent posterior decompressive laminectomy for cervical
      stenosis. The surgery took about 117 minutes and it was uneventful.
      Postoperatively he developed hoarseness of voice during speech, with deviation of
      tongue protrusion. On laryngoscopic examination, paralysis of the left side of
      the tongue and the soft palate was found and complete palsy of the left vocal
      cord was noted. After excluding surgical cause and craniocervical lesion, a
      clinical diagnosis of Tapia syndrome was made. Here we report a rare case of
      Tapia syndrome developed after posterior approach for cervical spine surgery and
      discuss the possible mechanisms of this uncommon syndrome. 

PMID- 24891859
TI  - Lumbar spinal chondroma presenting with acute sciatica.
AB  - A 47-year-old woman visited with lumbago and severe left leg pain that had been
      presented for 1 week. The patient complained of severe radiating pain on left L3
      sensory dermatome area and reported aggravation of leg pain at 20 degrees of hip
      flexion by straight leg raising test (SLRT). However, there was no motor weakness
      on neurological examination. Magnetic resonance imaging (MRI) demonstrated
      contrast enhancing spinal extradural mass at L2-3 level that was iso-signal
      intensity (SI) on T1-weighted images (WI), hypo-SI on T2WI. She was not able to
      walk and sleep due to incapacitating pain. Thus, surgical removal was performed
      via left partial laminectomy. Postoperatively, the radiating pain was relieved
      completely. Histopathologic examination revealed that the tumor consisted of
      chondroma, which had mature hyaline cartilage with nests of benign-appearing
      cells and calcium deposits in lacunae. 

PMID- 24891860
TI  - Large spinal meningioma with hemorrhage after selective root block in the thoraco
      lumbar spine.
AB  - Spinal meningioma accounts for 25% of all spinal cord tumors and occurs mostly in
      the thoracic region. Spontaneous intraspinal bleeding associated with spinal
      meningioma has rarely been reported. Most cases of hemorrhage associated with
      meningiomas are extratumoral and subarachnoid, whereas subdural and intratumoral
      hemorrhage cases have been reported to occur rarely. We experienced a case of a
      58-year-old woman with thoracolumbar spinal meningioma accompanied by intraspinal
      subdural hematoma. She presented with progressively worsened back pain and newly
      developed weakness in the right lower extremity after a selective nerve root
      block in the lumbar spine. She underwent the operation and progressively showed
      neurological recovery during the postoperative course. We report a
      thoracolumbarspinal meningioma with subdural and intratumoral hemorrhage after a
      spinal procedure that caused a sudden neurological deterioration. 

PMID- 24891861
TI  - Vertebral artery dissect injury with brown-sequard syndrome by a neural foramen
      penetrated electric screw driver bit : a case report.
AB  - There are few reports in the literature of complete obstruction of the vertebral
      artery (VA) due to an electric screw driver bit penetration through the neural
      foramen into the spinal canal with Brown-Sequard syndrome (BSS). A 25-year-old
      man was admitted to the emergency department with a penetrated neck injury by an
      electric screw driver bit after a struggle. The patient presented the clinical
      features of BSS. Computed tomography scan revealed that the electric screw driver
      bit penetrated through the right neural foramen at the level of C3-4, and it
      caused an injury to the right half of the spinal cord. Emergent angiography
      revealed VA dissection, which was managed by immediate coil embolization at both
      proximal and distal ends of the injury site. After occlusion of the VA, the
      electric screw driver bit was extracted under general anesthesia. Bleeding was
      minimal and controlled without difficulties. No postoperative complications, such
      as wound dehiscence, CSF leakage, or infection, were noted. Endovascular
      approaches for occlusion of vertebral artery lesions are safe and effective
      methods of treatment. 

PMID- 24891862
TI  - Abdominal aortic aneurysm presenting as a claudication.
AB  - Back pain and radiating pain to the legs are the most common symptoms encountered
      in routine neurosurgical practice and usually originates from neurogenic causes
      including spinal stenosis. The clinial symptoms are often confused with symptoms
      of peripheral neuropathy, musculo-skeletal disease and vascular disease in
      elderly patients. Because it is not easy to distinguish out the cause of symptoms
      by only physical examination, routine spinal MRI is checked first to rule out the
      spinal diseases in most outpatient clinics. Although it is obvious that spinal
      MRI is a very strong tool to investigate the spinal circumferences, most spine
      surgeons ignore the importance of looking at all aspects of their imaging and of
      remembering the extra-spinal causes of radiculopathy. A 68-year-old man who
      presented with a sudden aggravated both leg claudication. Although his symptom
      was mimicked for his long standing neurogenic claudication due to spinal stenosis
      diagnosed previously, abdominal aortic aneurysm(AAA) was found on routine lumbar
      MRI and it was repaired successfully. We emphasize to spinal surgeons the
      importance of remembering to look wider on routine MRI images when considering
      differential diagnoses in the outpatient clinic and to remember the extra-spinal
      causes of radiculopathy, especially when encountering in elderly patients. 

PMID- 24891863
TI  - Endovascular management of great vessel injury following lumbar microdiscectomy.
AB  - Great vessel injury is a rare but well-known complication of lumbar disc surgery,
      which may result in acute or fatal outcomes of delayed diagnosis. Thus, early
      detection and proper management is vital. The authors report a case of
      retroperitoneal hemorrhage with arteriovenous fistula and pseudoaneurysm after
      lumbar microdiscectomy. The patient was successfully managed by endovascular
      intervention using a stent graft. Endovascular repair is a minimally invasive and
      efficient treatment modality with considerably low morbidity and mortality. 

PMID- 24891864
TI  - Long term effect on adjacent segment motion after posterior cervical
      foraminotomy.
AB  - OBJECTIVE: Posterior cervical foraminotomy (PCF) is a motion-preserving surgical
      technique. The objective was to determine whether PCF alter cervical motion as a
      long-term influence. METHODS: Thirty one patients who followed up more than 36
      months after PCF for cervical radiculopathy from January 2004 to September 2008
      were enrolled in this study. The range of motion (ROM) of whole cervical spine,
      the operated segment, the cranial and the caudal adjacent segment were obtained.
      The clinical result and the change of ROMs were compared with those in the
      patients performed anterior cervical discectomy and fusion (ACDF) during the same
      period. RESULTS: In PCF group, the ROM of whole cervical spine had no significant
      difference in statistically at preoperative and last follow up. The operated
      segment ROM was significantly decreased from 11.02+/-5.72 to 8.82+/-6.65
      (p<0.05). The ROM of cranial adjacent segment was slightly increased from 10.42+/
      5.13 to 11.02+/-5.41 and the ROM of caudal adjacent segment was decreased from
      9.44+/-6.26 to 8.73+/-5.92, however these data were not meaningful statistically.
      In ACDF group, the operated ROM was decreased and unlike in PCF group, especially
      the ROM of caudal adjacent segment was increased from 9.39+/-4.21 to 11.33+/-5.07
      (p<0.01). CONCLUSION: As part of the long-term effects of PCF on cervical motion,
      the operated segment motions decreased but were preserved after PCF. However,
      unlikely after ACDF, the ROMs of the adjacent segment did not increase after PCF.
      PCF, by maintaining the motion of the operated segment, imposes less stress on
      the adjacent segments. This may be one of its advantages.

PMID- 24891865
TI  - Repeated complication following atlantoaxial fusion: a case report.
AB  - A patients with atlantoaixial instability and osodontoideum underwent
      atlantoaixial fusion (Harms and Melcher technique) with demineralized bone
      matrix. But, unfortunately, the both pedicle screws in C2 were fractured within 9
      weeks follow-up periods after several suspected episode of neck hyper-flexion.
      Fractured screws were not contact to occipital bone in several imaging studies,
      but it could irritate the occipital bone when neck extension because the
      relatively close distance between the occipital bone and C1 posterior arch. The
      patient underwent revision operation with translaminar screw fixation with
      autologus iliac bone graft. Postsurgical course were uneventful except donor site
      pain, but the bony fusion was not satisfied after 4 months follow-up. The patient
      re-underwent revision operation in other hospital. Continuous complication after
      atlantoaixial fusion is rare, but the clinical course could be unlucky to
      patients. Postoperative immobilization could be important to prevent the
      unintended clinical course of patients. 

PMID- 24891866
TI  - Spinal subdural hematoma following meningioma removal operation.
AB  - Although blood contamination of cerebrospinal fluid (CSF) after an intracranial
      operation can occur, the development of a symptomatic spinal hematoma after
      craniotomy has been anecdotally reported and it is uncommon reported after a
      supratentorial meningioma removal operation. We report a case of spinal subdural
      hematoma following a supratentorial meningioma removal operation and discuss the
      mechanism of spinal subdural hematoma (SSDH) development. A 54-year-old woman
      presented with lumbago and radicular pain on both legs 4 days after a right
      parietooccipital craniotomy for meningioma removal. Only the straight leg raising
      sign was positive on neurologic examination but the magnetic resonance imaging
      (MRI) demonstrated a lumbosacral spinal subdural hematoma. The patient received
      serial lumbar tapping, after which her symptoms showed improvement. 

PMID- 24891867
TI  - Crowned dens syndrome: a case report and review of the literature.
AB  - The crowned dens syndrome (CDS), also known as periodontoid calcium pyrophosphate
      dehydrate crystal deposition disease, is typified clinically by severe cervical
      pain, neck stiffness and atlantoaxial synovial calcification which could be
      misdiagnosed as meningitis, epidural abscess, polymyalgia rheumatica, giant cell
      arthritis, rheumatoid arthritis, cervical spondylitis or metastatic spinal tumor.
      Crystalline deposition on cervical vertebrae is less well known disease entity
      and only a limited number of cases have been reported to date. Authors report a
      case of CDS and describe the clinical feature. 

PMID- 24891868
TI  - Ligamentum flavum cyst of lumbar spine: a case report and literature review.
AB  - Ligamentum flavum cysts have rarely been reported and known to be the uncommon
      cause of spinal compression and radiculopathy. A 63-year-old man presented right
      sciatica lasting for 1 month. Lumbar computerized tomography and magnetic
      resonance imaging demonstrated an extradural cystic mass adjacent to the L5-S1
      facet joints. Partial hemilaminectomy and flavectomy at the L5-S1 space were
      performed, and then the cystic mass was excised. Histopathology confirmed a
      connective tissue cyst, which is consistent with the ligamentum flavum.
      Microscopic examination of the cyst wall revealed that it is closely packed
      collagen fibril. The symptom of patient was improved after surgery. Because of
      rarity of ligamentum flavum cysts and nonspecific clinical and radiologic
      findings, the preoperative diagnosis is not easy. The histologic features of
      ligamentum flavum cysts are distinct from other cystic lesion of lumbar spine.
      This study presents a case and literature review of ligamentum flavum cyst. We
      summarize the pathophysiology, occurrence, differential diagnosis of rare
      ligamentum flavum cyst, especially on lumbar spine. 

PMID- 24891869
TI  - Late infection from anterior cervical discectomy and fusion after twenty years.
AB  - Anterior cervical discectomy and fusion (ACDF) has been performed for
      degenerative and traumatic cervical diseases to improve pain and neurologic
      symptoms including sensory change and motor weakness. Infection, however, is a
      rare complication of ACDF, and late infection is even much rarer. We present a
      case of late Infection from ACDF C4-5 using Biocompatible Osteoconductive Polymer
      (BOP) after twenty years in the absence of an esophageal perforation, Zenker's
      diverticulum, or recent surgery or bacteremia. Late infection from ACDF after 20
      years is extremely rare in the literature. However, possibility of such a late
      complication should be appreciated during the follow-up period and surgical
      resection will be required for proper treatment. 

PMID- 24891871
TI  - Evidence-Based ZHENG: A Traditional Chinese Medicine Syndrome 2013.

PMID- 24891870
TI  - Design of glucagon-like Peptide-1 receptor agonist for diabetes mellitus from
      traditional chinese medicine.
AB  - Glucagon-like peptide-1 (GLP-1) is a promising target for diabetes mellitus (DM)
      therapy and reduces the occurrence of diabetes due to obesity. However, GLP-1
      will be hydrolyzed soon by the enzyme dipeptidyl peptidase-4 (DPP-4). We tried to
      design small molecular drugs for GLP-1 receptor agonist from the world's largest
      traditional Chinese medicine (TCM) Database@Taiwan. According to docking results
      of virtual screening, we selected 2 TCM compounds, wenyujinoside and 28
      deglucosylchikusetsusaponin IV, for further molecular dynamics (MD) simulation.
      GLP-1 was assigned as the control compound. Based on the results of root mean
      square deviation (RMSD), solvent accessible surface (SAS), mean square deviation
      (MSD), Gyrate, total energy, root mean square fluctuation (RMSF), matrices of
      smallest distance of residues, database of secondary structure assignment (DSSP),
      cluster analysis, and distance of H-bond, we concluded that all the 3 compounds
      could bind and activate GLP-1 receptor by computational simulation. Wenyujinoside
      and 28-deglucosylchikusetsusaponin IV were the TCM compounds that could be GLP-1
      receptor agonists. 

PMID- 24891872
TI  - Special invertebrate models and integrative medical applications: regulations,
      mechanisms, and therapies.

PMID- 24891873
TI  - American Ginseng Extract (Panax quinquefolius L.) Is Safe in Long-Term Use in
      Type 2 Diabetic Patients.
AB  - Aim. The objective of the present study was to test the safety of supplementation
      with the American ginseng (AG) interventional material as an adjunct to
      conventional therapy (diet and/or medications) in type 2 diabetes, using a double
      blind, randomized, placebo-controlled, parallel design. Methods. Each participant
      received either AG (10% ginsenosides) or placebo capsules (500 mg/meal = 3 g/day)
      for a period of 12 weeks. Outcomes included measures of safety including kidney
      function (urates and creatinine), liver function (AST and ALT), and haemostatic
      function (PV and INR). Results. Seventy-four participants with well-controlled
      type 2 diabetes (sex: 28 M and 46 F, age: 63 +/- 9.5, BMI: 32 +/- 5, and HbA1c: 7
      +/- 1.3), randomized to either intervention (n = 35) or control (n = 39) group,
      completed the study. There was no change in any of the measures of safety between
      treatments from baseline. The number or severity of adverse events did not differ
      between the AG intervention and placebo. Conclusion. Following 12 weeks of
      supplementation with AG, safety was not compromised in a high cardiovascular
      disease (CVD) risk population of patients with type 2 diabetes. This demonstrated
      that safety is noteworthy, as reviews have continuously warned of possible
      adverse effects of ginseng consumption. 

PMID- 24891874
TI  - Litter size manipulation in laboratory mice: an example of how proteomic analysis
      can uncover new mechanisms underlying the cost of reproduction.
AB  - BACKGROUND: Life history theories predict that investment in current reproduction
      comes at a cost for future reproduction and survival. Oxidative stress is one of
      the best documented mechanisms underlying costs of reproduction to date. However,
      other, yet to be described molecular mechanisms that play a short term role
      during reproduction may explain the negative relationships underlying the cost of
      reproduction. To identify such new mechanisms, we used a global proteomic
      determination of liver protein profiles in laboratory adult female mice whose
      litter size had been either reduced or enlarged after birth. This litter size
      manipulation was expected to affect females by either raising or decreasing their
      current reproductive effort. At the same time, global parameters and levels of
      oxidative stress were also measured in all females. RESULTS: Based on plasma
      analyses, females with enlarged litters exhibited increased levels of oxidative
      stress at the date of weaning compared to females with reduced litters, while no
      significant difference was found between both the latter groups and control
      females. None of the liver proteins related to oxidative balance were
      significantly affected by the experimental treatment. In contrast, the liver
      protein profiles of females with enlarged and reduced litters suggested that
      calcium metabolism and cell growth regulation were negatively affected by changes
      in the number of pup reared. CONCLUSIONS: Plasma oxidative stress levels in
      reproductive mice revealed that the degree of investment in reproduction can
      actually incur a cost in terms of plasmatic oxidative stress, their initial
      investment in reproduction being close to maximum and remaining at a same level
      when the energy demand of lactation is reduced. Liver proteomic profiles in
      reproductive females show that hepatic oxidative stress is unlikely to be
      involved in the cost of reproduction. Reproductive females rather exhibited liver
      protein profiles similar to those previously described in laboratory ageing mice,
      thus suggesting that hepatic cell pro-ageing processes may be involved in the
      cost of reproduction. Overall, our data illustrate how a proteomic approach can
      unravel new mechanisms sustaining life-history trade-offs, and reproduction costs
      in particular.

PMID- 24891875
TI  - Quantifying and understanding carbon storage and sequestration within the Eastern
      Arc Mountains of Tanzania, a tropical biodiversity hotspot.
AB  - BACKGROUND: The carbon stored in vegetation varies across tropical landscapes due
      to a complex mix of climatic and edaphic variables, as well as direct human
      interventions such as deforestation and forest degradation. Mapping and
      monitoring this variation is essential if policy developments such as REDD+
      (Reducing Emissions from Deforestation and Forest Degradation) are to be known to
      have succeeded or failed. RESULTS: We produce a map of carbon storage across the
      watershed of the Tanzanian Eastern Arc Mountains (33.9 million ha) using 1,611
      forest inventory plots, and correlations with associated climate, soil and
      disturbance data. As expected, tropical forest stores more carbon per hectare
      (182 Mg C ha(-1)) than woody savanna (51 Mg C ha(-1)). However, woody savanna is
      the largest aggregate carbon store, with 0.49 Pg C over 9.6 million ha. We
      estimate the whole landscape stores 1.3 Pg C, significantly higher than most
      previous estimates for the region. The 95% Confidence Interval for this method
      (0.9 to 3.2 Pg C) is larger than simpler look-up table methods (1.5 to 1.6 Pg C),
      suggesting simpler methods may underestimate uncertainty. Using a small number of
      inventory plots with two censuses (n = 43) to assess changes in carbon storage,
      and applying the same mapping procedures, we found that carbon storage in the
      tree-dominated ecosystems has decreased, though not significantly, at a mean rate
      of 1.47 Mg C ha(-1) yr(-1) (c. 2% of the stocks of carbon per year). CONCLUSIONS:
      The most influential variables on carbon storage in the region are anthropogenic,
      particularly historical logging, as noted by the largest coefficient of
      explanatory variable on the response variable. Of the non-anthropogenic factors,
      a negative correlation with air temperature and a positive correlation with water
      availability dominate, having smaller p-values than historical logging but also
      smaller influence. High carbon storage is typically found far from the commercial
      capital, in locations with a low monthly temperature range, without a strong dry
      season, and in areas that have not suffered from historical logging. The results
      imply that policy interventions could retain carbon stored in vegetation and
      likely successfully slow or reverse carbon emissions.

PMID- 24891876
TI  - Prevalence of HPV infection and other risk factors in a Fijian population.
AB  - BACKGROUND: Cancer is among the leading contributors to morbidity and mortality
      in the Pacific, but the magnitude of the problem and the potential for prevention
      have not been comprehensively studied. Over the past decade, cervical cancer has
      been the most common cancer among women in Fiji with an age standardised cervical
      cancer incidence rate of 51 per 100,000. This rate is among the highest in the
      South Pacific region and in the world. This high cervical cancer incidence rate
      is likely linked to the low cervical screening rate, but it points also to the
      possibility of a high burden of human papillomavirus (HPV) infection. METHODS: We
      conducted a population-based survey in Fiji to provide information on human
      papillomavirus (HPV) prevalence, and the distribution of individual HPV types in
      a Fijian health-sub-district. We included 1,261 women aged between 16 and 64
      years. A general primer GP5+/6+ mediatedpolymerase chain reaction (PCR) assay was
      used for HPV testing of 44 HPV types. RESULTS: The crude HPV prevalence in 1,244
      women with an adequate HPV sample was 24.0% (95% confidence interval (CI), 21.7
      26.4%) and the corresponding age standardised prevalence was 25.5% (95% CI, 23.1
      28.1%). The prevalence of high-risk HPV types was 13.6% (95% CI, 11.8-15.6%).
      Among 1,192 women with adequate cytological results, 13 (1.1%) showed cervical
      abnormalities, the majority of which were high-grade intraepithelial lesions or
      worse. HPV prevalence declined from 35.8% in women aged <25 years to 18.6% in
      those aged 55-64 years of age. After adjustment, the only variables significantly
      associated with HPV-positivity were age (ranging from odds ratio (OR) 0.57 (95%
      CI, 0.36-0.89) for 25-34 year-old-women to OR 0.43 (95% CI, 0.20-0.89) for 55-64
      year-old-women) and 'husband's extramarital sexual relationships' (OR 1.69; 95%
      CI, 1.17-2.34). CONCLUSION: These findings on HPV provide key information for
      future policy decisions on the most appropriate methods of cervical cancer
      prevention in Fiji and in the Pacific region.

PMID- 24891878
TI  - Blood glucose lowering activity of aloe based composition, UP780, in alloxan
      induced insulin dependent mouse diabetes model.
AB  - BACKGROUND: There are a few nutritional approaches to address the increased needs
      of managing diabetic conditions. Previously it has been reported that UP780, a
      standardized composition of aloe chromone formulated with an aloe polysaccharide,
      has a significant impact in reducing HbA1C, fasting blood glucose, fructosamine
      and plasma insulin level in humans and improved impaired glucose and insulin
      resistance in high-fat diet-induced and db/db non-insulin dependent diabetic
      mouse models. Here we describe activity of UP780 and its constituents to improve
      insulin sensitivity in alloxan induced insulin dependent diabetic mouse model.
      MATERIALS AND METHOD: Insulin dependent diabetes was induced by administering a
      single intraperitoneal injection of alloxan monohydrate at a dose of 150 mg/kg to
      CD-1 mice. Aloesin (UP394) was formulated with an Aloe vera inner leaf gel powder
      polysaccharide (Qmatrix) to yield a composition designated UP780. Efficacy of
      oral administration of UP780 at 2000 mg/kg and its constituents (aloesin at 80
      mg/kg and Qmatrix at 1920 mg/kg) were evaluated in this model. Glyburide, a
      sulfonylurea drug used in the treatment of type 2 diabetes, was used at 5 mg/kg
      as a positive control. Effect of UP780 on non-diabetic normal mice was also
      addressed. RESULTS: Mice administered intraperitoneal alloxan monohydrate
      developed progressive type-1 diabetes like symptom. After 4 weeks of daily oral
      administration, reductions of 35.9%, 17.2% and 11.6% in fasting blood glucose
      levels were observed for UP780, the UP780 Aloe vera inner leaf gel polysaccharide
      preparation without chromone (Qmatrix), and Aloesin (UP394), treated animals
      respectively, compared to vehicle treated animals. UP780 has no impact on blood
      glucose level of non-diabetic healthy mice. UP780 showed statistically
      significant improvement for blood glucose clearance in oral glucose tolerance
      tests. Similarly, enhanced improvement in plasma insulin level and statistically
      significant reduction in triglyceride level was also observed for animals treated
      with the composition. CONCLUSION: These findings suggest that UP780, a chromone
      standardized Aloe based composition, could possibly be used as a natural
      supplement alternative to facilitate maintenance of healthy blood glucose levels.

PMID- 24891877
TI  - Lung epithelial stem cells and their niches: Fgf10 takes center stage.
AB  - Throughout life adult animals crucially depend on stem cell populations to
      maintain and repair their tissues to ensure life-long organ function. Stem cells
      are characterized by their capacity to extensively self-renew and give rise to
      one or more differentiated cell types. These powerful stem cell properties are
      key to meet the changing demand for tissue replacement during normal lung
      homeostasis and regeneration after lung injury. Great strides have been made over
      the last few years to identify and characterize lung epithelial stem cells as
      well as their lineage relationships. Unfortunately, knowledge on what regulates
      the behavior and fate specification of lung epithelial stem cells is still
      limited, but involves communication with their microenvironment or niche, a local
      tissue environment that hosts and influences the behaviors or characteristics of
      stem cells and that comprises other cell types and extracellular matrix. As such,
      an intimate and dynamic epithelial-mesenchymal cross-talk, which is also
      essential during lung development, is required for normal homeostasis and to
      mount an appropriate regenerative response after lung injury. Fibroblast growth
      factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling
      pathway governing epithelial-mesenchymal interactions during lung development as
      well as between different adult lung epithelial stem cells and their niches. On
      the other hand, disruption of these reciprocal interactions leads to a
      dysfunctional epithelial stem cell-niche unit, which may culminate in chronic
      lung diseases such as chronic obstructive pulmonary disease (COPD), chronic
      asthma and idiopathic pulmonary fibrosis (IPF). 

PMID- 24891881
TI  - Long-term inflammation in the temporal artery of a giant cell arteritis patient
      as detected by ultrasound.

PMID- 24891882
TI  - Fluidity of the body.

PMID- 24891880
TI  - Biological therapies for spondyloarthritis.
AB  - Biological therapies and new imaging techniques have changed the therapeutic and
      diagnostic approach to spondyloarthritis. In patients with axial
      spondyloarthritis, tumor necrosis factor alpha (TNFalpha) inhibitor treatment is
      currently the only effective therapy in patients for whom conventional therapy
      with nonsteroidal anti-inflammatory drugs (NSAIDs) has failed. TNFalpha inhibitor
      treatment is more effective in preventing articular damage in peripheral joints
      than in axial ones. It is important to treat patients at an early stage of
      disease to reduce disease progression; moreover it is necessary to identify
      causes of therapy inefficacy in preventing joint damage in the axial subset. 

PMID- 24891879
TI  - The osteocyte as a therapeutic target in the treatment of osteoporosis.
AB  - Osteoporosis is characterized by a low bone-mineral density associated with
      skeletal fractures. The decrease in bone-mineral density is the consequence of an
      unbalanced bone-remodeling process, with higher bone resorption than bone
      formation. The orchestration of the bone-remodeling process is under the control
      of the most abundant cell in bone, the osteocyte. Functioning as an endocrine
      cell, osteocytes are also a source of soluble factors that not only target cells
      on the bone surface, but also target distant organs. Therefore, any drugs
      targeting the osteocyte functions and signaling pathways will have a major impact
      on the bone-remodeling process. This review discusses potential advances in drug
      therapy for osteoporosis, including novel osteocyte-related antiresorptive and
      anabolic agents that may become available in the coming years. 

PMID- 24891883
TI  - Use of pipeline flow diverting stents for wide neck intracranial aneurysms: A
      retrospective institutional review.
AB  - BACKGROUND: Intracranial aneurysms (ICA) if inadequately treated may result in
      serious morbidity and mortality. Wide-neck; large/giant, fusiform, and dissecting
      aneurysms are not well treated using the conventional coil embolization
      technique. Recent advance in endovascular treatment and technology has introduced
      flow diverter devices including pipeline embolization devices (PED) and Silk
      stents that have been shown to be more effective in treating these more
      complicated aneurysms. Flow Diverter devices offer a more physiologic approach to
      ICA treatment. METHODS: We conducted a retrospective chart review of 23 adult
      patients who underwent aneurysm treatment utilizing the pipeline stent at Duke
      University Medical Center from July 2011 to March 2013. RESULTS: Majority of
      patients (19, 82.7%) showed angiographic evidence of complete obliteration of
      aneurysm at 6 months follow-up, with sustained clinical improvement on modified
      Rankin scale score. All of the patients tolerated the procedure well with no
      intra-operative hemorrhage or intra-operative thromboembolic complications.
      CONCLUSIONS: Our experience shows that use of PED offers a safe and effective
      strategy for treatment of complex ICA. Larger prospective studies are needed to
      confirm these observations.

PMID- 24891884
TI  - Microgravity environment and compensatory: Decompensatory phases for intracranial
      hypertension form new perspectives to explain mechanism underlying communicating
      hydrocephalus and its related disorders.
AB  - The pathogenesis underlying communicating hydrocephalus has been centered on
      impaired cerebrospinal fluid (CSF) outflow secondary to abnormal CSF pulsation
      and venous hypertension. Hydrodynamic theory of hydrocephalus fares better than
      traditional theory in explaining the possible mechanisms underlying communicating
      hydrocephalus. Nonetheless, hydrodynamic theory alone could not fully explain
      some conditions that have ventriculomegaly but without hydrocephalus. By
      revisiting brain buoyancy from a fresher perspective, called microgravity
      environment of the brain, introducing wider concepts of anatomical and
      physiological compensatory-decompensatory phases for a persistent raise in
      intracranial pressure, and along with combining these two concepts with the
      previously well-accepted concepts of Monro-Kellie doctrine, intracranial
      hypertension, cerebral blood flow, cerebral perfusion pressure, brain compliance
      and elasticity, cerebral autoregulation, blood-brain and blood-CSF barriers,
      venous and cardiopulmonary hypertension, Windkessel phenomenon, and cerebral
      pulsation, we provide plausible explanations to the pathogenesis for
      communicating hydrocephalus and its related disorders. 

PMID- 24891885
TI  - Keyhole concept in cerebral aneurysm clipping and tumor removal by the
      supraciliary lateral supraorbital approach.
AB  - The keyhole concept in neurosurgery is designed to minimize the craniotomy needed
      for the access route to deep intracranial pathologies. Such keyhole surgeries
      cause less trauma and can be less invasive than conventional surgical techniques.
      Among the various types of keyhole mini-craniotomy, supraorbital or lateral
      supraorbital mini-craniotomy is the standard and basic keyhole approaches. The
      lateral supraorbital keyhole provides adequate working space in the suprasellar
      to parasellar areas and planum sphenoidale area including the anterior
      communicating artery complex. Despite the development of neuro-endoscopic
      techniques and intra-operative assistant methods, the limited working angle to
      manipulate and observe deeply situated pathologies is a major disadvantage of the
      keyhole approaches. Neurosurgeons should understand that keyhole mini-craniotomy
      surgeries aim at "minimally invasive neurosurgery" but still carry the risks of
      malpractice unless we understand the advantages and disadvantages of these
      keyhole concepts and strategies. 

PMID- 24891886
TI  - Clinico-radiological profile and nuances in the management of cervicomedullary
      junction intramedullary tumors.
AB  - BACKGROUND: Cervicomedullary junction (CMJ) intramedullary tumors comprise of
      tumors that often pose a surgical challenge even in the present era. Though
      classified under brainstem glioma CMJ tumors are well amenable for surgical
      resection and have a good outcome. Various factors are involved in the outcome of
      these patients following surgery and a proper pre-operative assessment is often
      required to reduce the morbidity and mortality. MATERIALS AND METHODS: Patients
      admitted in the Department of Neurosurgery with a diagnosis of CMJ intramedullary
      tumors from January 2001 to January 2010 were included in the study. Patients
      were analyzed retrospectively regarding their symptomatology, clinical findings,
      radiology and outcome after surgery. All patients underwent pre-operative
      magnetic resonance imaging (MRI) and post-operatively all were managed in the
      neurosurgery intensive care unit for days to weeks or as dictated by the clinical
      condition of the patient. RESULTS: A total of 32 patients were included in the
      present study. The number of males was 21 (65.6%) and females were 11 (34.4%)
      respectively. The mean age of presentation was 22.97 +/- 9.8 years and the mean
      duration of pre-operative symptoms was 13.3 +/- 12.9 months. The tumor had
      extension from the CMJ into the cervical region in 17 (53.1%) and into the
      medullary region in 14 (43.8%) patients. Tumor decompression was done in 9
      (28.1%) patients and gross near total excision done in 23 (71.87%) patients.
      CONCLUSIONS: Cervicomedullary tumors are a subset of tumors quite distinct from
      the usual brainstem tumors. Patients having predominant cervical involvement
      present early and have less post-operative deficits. Those with predominantly
      more medullary involvement present late, hence have a much more morbid outcome.
      Though closely related to vital neural structures, surgery forms the mainstay of
      treatment. Adequate pre-operative planning and preparation of the patient along
      with intense post-operative monitoring and ventilatory assistance as and when
      required helps in a good surgical outcome.

PMID- 24891887
TI  - Cognitive and sexual functions in patients with traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) has an immense psychosocial impact on an
      individual as well as on the close relatives. Sexuality is one among the
      functions which are usually found compromised post injury. The aim of present
      study was to examine cognitive and sexual functions post TBI. The objective of
      the study was to explore these domains and their relationship with each other.
      TOOLS: The tools used were sociodemographics record sheet, Edinburg handedness
      inventory, brief sexual function inventory, depression anxiety stress scales-21
      and NIMHANS head injury battery. The sample consisted of 30 patients with mild-to
      moderate TBI. All the subjects were tested individually in their regional
      language. RESULTS: On cognitive domain, patients performed inadequately on all
      the tests; however, the percentage was higher in mental speed (43.3%), sustained
      attention (26.7%), verbal working memory (30%), response inhibition (36.7%),
      verbal memory (immediate and delayed) (43%) and visual (immediate, 23.3% and
      delayed, 26.7%). On the domain of sexual functions, all the four domains (sexual
      drive, erection, ejaculation and problem assessment) were affected however
      overall satisfaction (93.3%) was adequate. Among the four domains higher
      percentage of involvement was noted on problem assessment (70%), ejaculation
      (56.7%), and erection (46.7%). Significant correlation was found between mental
      speed, verbal working memory, planning, and visual memory with sexual drive,
      erection, ejaculation and overall satisfaction domains of sexual functioning.
      Negative correlation was found between motor speed and sustained attention with
      sexual drive, erection and ejaculation. CONCLUSION: Both cognitive and sexual
      functioning were found effected post TBI. However less emphasis is given to
      sexual functioning by the professionals. Educational intervention is needed to
      sensitize professional about this area and to include this area for better
      management.

PMID- 24891888
TI  - Rapid ventricular pacing assisted hypotension in the management of sudden
      intraoperative hemorrhage during cerebral aneurysm clipping.
AB  - Sudden intraoperative hemorrhage during intracranial aneurysm surgery from
      vascular injury or aneurysmal rupture has been known to dramatically increase the
      associated morbidity and mortality. We describe the first reported use of rapid
      ventricular pacing (RVP) assisted hypotension to control sudden intraoperative
      hemorrhage during intracranial aneurysm surgery where temporary arterial
      occlusion was not achievable. 

PMID- 24891889
TI  - Intramedullary melanocytoma of thoracic spine: A rare case report.
AB  - Melanocytomas are present in leptomeninges and arise from neural crest during
      early embryonic development. They are a rare entity and usually occur in the
      thoracic spine and infratentorial region. We report a 32-year-old female with
      meningeal melanocytoma of D9-10. Magnetic resonance imaging revealed an
      intramedullary spinal tumor at D9-D10. Intraoperatively, the tumor was greyish
      black in color with moderate vascularity, and was adherent to the cord. The
      clinical differential diagnoses included cavernoma and melanocytoma. On
      microscopic examination, the lesion showed sheets of cells with marked pigment
      deposition, which was obscuring the cellular morphology. The pigment was
      confirmed to be melanin by Masson's Fontana stain. Immunohistochemistry was
      performed, which showed positivity for HMB-45, S-100, Vimentin and Melan-A. The
      cells were negative for cytokeratin, epithelial membrane antigen, Glial
      fibrillary acidic protein and neuron-specific enolase. Mib-1 labeling index was
      less than 1%. In view of the lack of nuclear atypia, mitoses, necrosis and low
      Mib-1-labeling index along with immunohistochemistry profile, the diagnosis of
      Melanocytoma was made. Melanocytomas are rare pigmented tumors of the spinal cord
      and posterior cranial fossa. They are benign in nature, but can also be locally
      aggressive. Melanocytic lesions of the nervous system are to be differentiated
      from metastatic melanomas and also tumors showing melanin pigment deposition like
      schwanomma, paraganglioma, medulloblastoma and various gliomas. 

PMID- 24891890
TI  - Brown tumor as an unusual but preventable cause of spinal cord compression: Case
      report and review of the literature.
AB  - Brown tumor (BT), also known as osteoclastoma, may appear in the context of
      primary and secondary hyperparathyroidism. Spinal cord compression due to the BT
      is extremely rare. We present here an unusual case of BT involving thoracal spine
      and mandible. A 26-year-old woman, who had been on hemodialysis for chronic renal
      failure for over 6 years, got admitted with dorsal pain and progressive weakness
      in her lower extremities and gait disturbances. Neurological examination revealed
      spastic paraparesis and symmetrically hyperactive tendon reflex in the lower
      extremities. She had hypoesthesia under T10 level. On physical examination, a
      swelling on the left side of her jaw was also detected. Magnetic resonance
      imaging (MRI) showed cord compression due to an extradural mass lesion at T8
      level. A computerized tomography (CT) scan showed that this expansile lytic
      lesion was caused by the collapse of vertebra corpus (T8) at that level. CT of
      the mandible revealed an expansile lytic lesion on left arm of the mandible.
      Laboratory findings were nearly normal except parathormone level elevation to
      1289 pg/mL (normal 30-70 pg/mL). Ultrasound examination showed enlargement of the
      parathyroid glands. The patient underwent an emergency decompression and
      stabilization surgery. The lesion was fragile and reddish in appearance and was
      easy to aspirate. The tumor was reported as "BT." Her weakness in the lower
      extremities improved in the early postoperative period. Following surgical
      intervention, the patient was transferred to nephrology clinic for additional
      medical treatment. 

PMID- 24891891
TI  - Atypical medulloblastoma: A case series.
AB  - Medulloblastoma is common in children as a tumor of midline posterior fossa,
      which arises from vermis and appears as a homogenously enhancing hyperdense mass
      on computed tomography scan and is associated with the clinical picture of
      posterior fossa syndrome. This unique clinic-radiological pattern in considered
      "typical" medulloblastoma, but medulloblastomas does not follow the typical
      clinic-radiological pattern in a significant number of children and adult cases.
      We review here the previous reports of atypical or uncommon features of
      medulloblastoma and add our very rare atypical cases of medulloblastomas to this
      list. Medulloblastoma should be considered in all midline posterior fossa tumors,
      hemisphere and cerebellopontine angle despite having clinical and radiological
      features suggestive of other tumors. Definitive diagnosis requires histologic
      confirmation in all cases. 

PMID- 24891892
TI  - Giant cell tumor of the clivus with presence of epithelioid histiocytes.
AB  - Giant cell tumor (GCT) is a benign neoplasm but locally aggressive tumor that
      uncommonly involves the skull bone. We report a case of a 62-year-old male
      presented with increasing headache and diplopia. Investigations were suggestive
      of an expanding mass lesion of the clivus. Histopathology was suggestive of
      diagnosed with GCT with abundant histiocytes. 

PMID- 24891893
TI  - Procedural sedation and analgesia in pediatric patients.
AB  - A spectrum of conditions requires sedation and analgesia in pediatric population.
      Ineffective treatment of pain may result in physiological and behavioral
      responses that can adversely affect the developing nociceptive system. The
      recognition of pain in children can be facilitated by different pain scales. This
      article reviews the procedural sedation and analgesia (PSA) practices in children
      along with pharmacology of the drugs used for this purpose. 

PMID- 24891894
TI  - Umbilical artery pH at birth and neurobehavioral outcome in early preterm
      infants: A cohort study.
AB  - OBJECTIVE: The objective of the following study is to determine the effect of
      umbilical artery pH at birth on early neurobehavioral outcome of preterm infants
      as assessed by Neurobehavioral Assessment of Preterm Infants (NAPI) tool.
      MATERIALS AND METHODS: Prospective cohort study conducted at the neonatal unit in
      a tertiary care center in North India. Preterm neonates < 34 weeks of gestation
      were enrolled at birth and divided into cases (umbilical artery pH < 7.2) and
      controls (umbilical artery pH > 7.2). At 34 weeks postconceptional age, the motor
      development and vigor (MDV) and alertness and orientation (AO) domains of
      neurobehavior were assessed by NAPI and compared among groups. RESULTS: Hundred
      preterm neonates were enrolled in the study out of which 76 (30 cases and 46
      controls) were finally analyzed. The groups were comparable in terms of
      gestational age, mode of delivery, birth weight and requirement of resuscitative
      measures at birth. There was no significant difference in incidence of
      meningitis, intraventricular hemorrhage, jaundice and hypoxic ischemic
      encephalopathy among the groups; however hypoglycemia was observed more commonly
      among cases. The MDV score (mean +/- standard deviation [SD] [95% confidence
      interval]) was found to be significantly lower among cases compared to controls
      (37.0713 +/- 13.616 [32.099-42.0431] vs. 47.506 +/- 14.0692 [43.367-51.655]) (P =
      0.002). Similarly, lower AO scores were observed among the cases. CONCLUSION: A
      low umbilical artery pH at birth is a predictor of poor early neurobehavioral
      outcome in preterm neonates.

PMID- 24891895
TI  - Menkes disease - An important cause of early onset refractory seizures.
AB  - CONTEXT: Menkes disease is an X-linked multisystem disorder characterized by
      early onset of cerebral and cerebellar neurodegeneration, fair skin,
      hypopigmented sparse hair and connective tissue abnormalities. AIMS: We aimed to
      evaluate the clinical, electrophysiological and radiological features of children
      with Menkes disease seen at our institute. SETTING/DESIGN: The medical records of
      children diagnosed with Menkes disease admitted in the pediatric neurology ward
      or attending the special pediatric neurology clinic at a tertiary care and a
      referral hospital in North India, from January 2010 to December 2012, were
      retrospectively reviewed. The clinical data of each case was subsequently
      summarized and reported. STATISTICAL ANALYSIS USED: Descriptive statistics were
      used. RESULTS: During the study period, 1174 children were seen. Out of these, 6
      cases were diagnosed as Menkes disease on the basis of clinical phenotype, low
      serum copper and ceruloplasmin and supportive neuroimaging. All the children were
      males and had disease onset within 3 months of age, with 4 children presenting in
      the neonatal period. Global developmental delay and refractory seizures were the
      predominant clinical symptoms. Two children had symptomatic West syndrome. Other
      seizure semiologies included tonic-clonic (4), myoclonic (2) and tonic seizures
      (1). The electroencephalographic abnormalities included hypsarrythmia (2) and
      multifocal epileptiform discharges (3). The salient radiological features
      included white matter changes, temporal lobe abnormalities, global atrophy,
      subdural hygromas and tortuous cerebral blood vessels. CONCLUSIONS: Menkes
      disease should be suspected in a case of refractory early onset seizures
      especially in the presence of subtle clinical clues. The neuroimaging findings
      may further support the diagnosis.

PMID- 24891896
TI  - Assessment of parent reported quality of life in children with epilepsy from
      Northern India: A cross-sectional study.
AB  - OBJECTIVE: The objective of the following study is to assess parent reported
      quality of life (QOL) in children with epilepsy and to assess the demographic and
      clinical factors, which influence the QOL in children with epilepsy. STUDY
      PARTICIPANTS: We consecutively enrolled 40 children aged from 2 years to 14 years
      with active epilepsy who had undergone a comprehensive evaluation for epilepsy.
      MATERIALS AND METHODS: Parents were enquired on baseline demographic variables
      including age, gender, socio-economic status and parental education. Clinical
      details of epilepsy including the type of epilepsy, seizure frequency were
      assessed. QOL was evaluated with the parent reported quality of life in childhood
      epilepsy (QOLCE) questionnaire. RESULTS: A total of 40 children were enrolled of
      which 55% (22/40) were males and the mean (standard deviation [SD]) age of
      enrolled children was 10.6 (2.7) years. The majority came from a rural background
      (80% [32/40]), were from lower (15 [37.5%]) or middle (23 [57.5%]) socio-economic
      status, with almost half (22 [55%]) of mothers being educated until high school.
      The overall mean (SD) QOL score was 66.7 (4.83). Lowest mean (SD) scores were
      observed in self-esteem (45.2 [7.3]) subscale and subscales with higher QOL
      scores included control/helplessness (82.1 [8.51]), anxiety (81.6 [12.55]) and
      social stigma (95.0 [11.6]). Parental education, socio-economic status (P =
      0.96), frequency of seizure (P = 0.34) or type of epilepsy (P = 0.92) did not
      significantly affect the overall QOL among children with epilepsy. CONCLUSION:
      Our study concluded that overall QOL was compromised in Indian children with
      epilepsy. Demographic factors like parental education, socio-economic status and
      clinical factors like frequency of seizure or type of seizure did not
      significantly affect the QOL of epileptic children.

PMID- 24891897
TI  - Infected lumbar dermoid cyst mimicking intramedullary spinal cord tumor:
      Observations and outcomes.
AB  - We report two unusual cases of a 17-month-old boy with a previously undiagnosed
      lumbar dermal sinus tract terminating in an intradural dermoid cyst and holocord
      edema or syrinx, presenting with paraparesis and sphincter dysfunction secondary
      to an intramedullary abscess and a 26-month-old boy with a previously undiagnosed
      lumbar dermal sinus tract terminating in an infected dermoid cyst and
      intramedullary abscess, presenting with recurrent episodes of meningitis and
      hydrocephalus. Pre-operative magnetic resonance imaging (MRI) studies in these
      patients were initially confused for an intramedullary spinal cord tumor;
      however, the presence of an associated dermal sinus tract made this diagnosis of
      neoplasm less likely. Total excision of the dermal sinus tract, debulking of the
      dermoid cyst and drainage of the intramedullary abscess through an L1-L5
      osteoplastic laminoplasty and midline myelotomy, followed by long-term antibiotic
      therapy resulted in a good functional recovery. Post-operative MRI of the spine
      showed removal of the dermoid cyst, decreased inflammatory granulation tissue and
      resolution of the holocord edema or syrinx. We also performed a literature review
      to determine the cumulative experience of management of intramedullary abscess in
      this rare clinical setting. 

PMID- 24891898
TI  - Aplasia cutis congenita associated with type I split cord malformation: Unusual
      case.
AB  - A full-term newborn girl born with large skin, muscle, bone and dural defect in
      the lumbo-sacral area. The lesion included a split spinal cord by a perpendicular
      bony spur and connected from its tip to the upper lamina. Patient was diagnosed
      with aplasia cutis congenita (ACC) associated with type I split cord malformation
      (SCM). Neurological examination of the lower extremities was normal. Spinal X
      rays showed a bony spur on the L2 vertebral column and laminar defect in the
      lumbo-sacral area. Lesion was operated and closed according to anatomic layers.
      Clinical and intraoperative findings of this extremely rare case are discussed. 

PMID- 24891899
TI  - Thoracic congenital dermal sinus associated with intramedullary spinal dermoid
      cyst.
AB  - Dorsal dermal sinus is a rare, congenital lesion found most frequently in the
      lumbosacral followed by the occipital regions. It is rarely localized at the
      thoracic level. We report a rare case of thoracic congenital dermal sinus (CDS)
      associated with an intramedullary dermoid cyst in a 2-year-old male child, who
      presented with a 3 month history of motor weakness of both the lower extremities.
      Magnetic resonance imaging (MRI) of spine showed an intramedullary dermoid cyst
      extending from the lower border of T4 to upper border of T7, which was connected
      with the skin dimple along the sinus tract. Total excision of the dermoid cyst
      and the sinus tract with T5-7 laminectomy resulted in good functional recovery. 

PMID- 24891900
TI  - Craniosynostosis in a child with I-cell disease: The need for genetic analysis
      before contemplating surgery in craniosynostosis.
AB  - We are reporting a rare case of I-cell disease presenting with craniosynostosis.
      An 11-month-old child presented with abnormal head shape, developmental delay and
      bent bones. We planned for corrective surgery for craniosynostosis, but on
      genetic analysis I-cell disease was confirmed. After explaining the prognosis of
      I-cell disease, parents denied surgery. This case report emphasizes the fact that
      syndromic evaluation of craniosynostosis is very much essential before proceeding
      for corrective surgery. 

PMID- 24891901
TI  - Unusual phenotype of glucose transport protein type 1 deficiency syndrome: A case
      report and literature review.
AB  - The glucose transport protein type 1 (GLUT1) deficit causes a chronic brain
      energy failure. The classic phenotype of GLUT1 deficiency syndrome is
      characterized by: Mild to severe motor delay and mental retardation; infantile
      onset epilepsy; head growth deceleration; movement disorders (ataxia, dystonia,
      spasticity); and non-epileptic paroxysmal events (intermittent ataxia, periodic
      confusion, recurrent headaches). During last years the classic phenotype of this
      syndrome, as originally reported, has expanded. We report the atypical phenotype
      of a boy with GLUT1 deficiency syndrome, characterized by mild mental retardation
      and drug-resistant absence seizures with onset at the age of 6 years, without
      movement disorders nor decrease of head circumference. A prompt diagnosis of this
      disorder is mandatory since the ketogenic diet might represent an effective
      treatment. 

PMID- 24891902
TI  - Paroxysmal vascular events in Sturge-Weber syndrome: Role of aspirin.
AB  - Sturge-Weber syndrome (SWS) is a rare, sporadically occurring neurocutaneous
      disorder with a frequency of approximately 1 per 50,000. The hallmark is an
      intracranial leptomeningeal vascular angioma in association with a port wine
      nevus, usually involving ophthalmic or maxillary distribution of trigeminal
      nerve. Other clinical findings associated with SWS are seizures, glaucoma,
      hemiparesis and mental retardation. The radiological hallmark is "Tram-line" or
      "Gyri-form" calcification. 25 to 56% of patients experience recurrent episodes of
      paroxysmal focal neurological deficits in form of transient hemiparesis, which
      may be due to vascular ischemia or postictal in origin. EEG helps to
      differentiate the exact etiology, as it is normal in former. Aspirin prophylaxis
      in those, due to ischemia decreases their recurrences and improves overall
      neurological prognosis. We report a 25-month-old child of SWS with recurrent
      episodes of transient hemiparesis and atypical midline location of facial
      vascular nevus. 

PMID- 24891903
TI  - Unusual presentation of poststreptococcal glomerulonephritis as posterior
      reversible encephalopathy syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a rare clinicoradiologic
      condition manifesting with headache, seizures, altered sensorium, visual
      disturbances, and characteristic lesions on neuroimaging predominantly affecting
      the posterior regions of the brain. We report a case of an 8-year-old boy with
      poststreptococcal glomerulonephritis, presenting as PRES. A magnetic resonance
      imaging showed hyperintense lesions in bilateral frontal and parietooccipital
      parenchyma on fluid-attenuated inversion recovery and T2-weighted images,
      suggestive of "PRES." Patient made a complete neurological recovery without any
      deficit. 

PMID- 24891904
TI  - Cerebral astroblastoma: A radiopathological diagnosis.
AB  - Astroblastoma is a rare glial neoplasm whose histogenesis has been clarified
      recently. It primarily occurs in children and young adults. We are reporting a
      case of 12-year-old girl child who presented with features of raised intracranial
      tension and generalized tonic-clonic seizures. Brain magnetic resonance imaging
      revealed a large well-circumscribed, cystic lesion without perifocal edema, and
      enhancing mural nodule in right parietal region. A radiological differential
      diagnosis of pilocytic astrocytoma and cerebral astroblastoma was made. A
      complete excision was done and histologically the lesion turned out to be an
      astroblastoma. We review the histology, immunohistochemistry, and imaging
      features of astroblastoma and survey the current literature, treatment
      strategies, and prognostic aspects for the management of this rare neoplasm. 

PMID- 24891905
TI  - Desmoplastic infantile ganglioglioma: Report of an unusual case with a cranial
      defect.
AB  - Desmoplastic infantile ganglioglioma (DIG) is a rare tumor that typically occurs
      in infants under the age of 24 months. These tumors commonly have a good
      prognosis after surgical resection despite their aggressive radiological
      appearances. Clinical signs are due to the large size of the tumor and include
      increased head circumference, bulging fontanel, sunset sign and seizures. We
      report an unusual DIG case who presented with parietal bulging associated with a
      bony defect. The patient was thought to have a leptomeningeal cystic formation,
      but on his cranial magnetic resonance imaging (MRI), we observed a centrally and
      homogeneously gadolinium-enhanced lesion fixed to the dura by its solid
      component. A surgical gross total resection was performed, and no residual tumor
      was observed on follow-up. 

PMID- 24891906
TI  - Intrinsic brainstem white epidermoid cyst: An unusual case report.
AB  - Epidermoid cysts involving the brainstem are extremely rare, with only 18
      reported cases in the literature and only five purely intrinsic epidermoid cysts
      within this group. "White epidermoids", a rare entity, have high protein content
      and show reversed signal intensity on magnetic resonance images. In contrast to
      the classical variety, these cysts show high signal intensity on T1-weighted
      images and low signal intensity on T2-weighted images. Here, we report an
      interesting case of intrinsic brainstem "white epidermoid cyst" in a 15-year-old
      girl and discuss its clinical characteristics, radiological features, and
      surgical treatment. The girl presented with a one-year history of progressive
      quadriparesis, and features of multiple cranial nerve involvement. Because the
      cyst was purely intrinsic and had altered signal intensity, the diagnosis was
      initially unclear until definitive neuroimaging was performed using diffusion
      weighted magnetic resonance imaging (DW-MRI) sequences. 

PMID- 24891907
TI  - Very severe spinal muscular atrophy: Type 0 with Dandy-Walker variant.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease
      characterized by degeneration of alpha motor neurons in the spinal cord,
      resulting in progressive proximal muscle weakness and paralysis. In addition to
      the three classical SMA types, a new form known as type 0 with intrauterine
      onset, profound hypotonia and a progressive and early fatal course has been
      described. Herein we report a case of type 0 SMA with a Dandy Walker variant
      anomaly, which has not hitherto been reported in the world literature. 

PMID- 24891908
TI  - Catatonia as presenting clinical feature of subacute sclerosing panencephalitis.
AB  - Catatonia is not a usual clinical presentation of subacute sclerosing
      panencephalitis (SSPE), especially in the initial stages of illness. However,
      there is only one reported case of SSPE presenting as catatonia among children.
      In this report, however, there were SSPE-specific changes on EEG and the
      catatonia failed to respond to lorazepam. We describe a case of SSPE in a child
      presenting as catatonia that presented with clinical features of catatonia and
      did not have typical EEG findings when assessed at first contact. He responded to
      lorazepam and EEG changes emerged during the course of follow-up. 

PMID- 24891909
TI  - Auto cannibalism in mental retardation.
AB  - Mental retardation (MR) deems an individual more vulnerable to psychopathologies.
      The individual may develop an array of behavioral disturbances manifesting
      themselves in the form of aggressive and destructive conduct, violent fits of
      anger, stereotyped, or self-injuring behavior. Self-injurious behavior is
      heterogeneous in nature ranging from mild to severe variant. We report a case of
      a 7-year-old boy with MR with self-inflicted severe oral injuries of
      cannibalistic nature presenting as cleft lip and palate. A more extensive
      research is needed on the problem behaviors in mentally retarded patients for
      early detection and effective and timely intervention leading to a better
      outcome. 

PMID- 24891910
TI  - A distinct phenotype of childhood leukodystrophy presenting as absence seizure.
AB  - Leukoencephalopathy refers to any disease of the white matter including
      hereditary as well as acquired and toxic causes. Inherited leukodystrophies are
      diseases of myelin including abnormal myelin development, hypomyelination, or
      degeneration of myelin. We report a 6-year old female who presented with absence
      seizure at the age of 4 years. Cerebral magnetic resonance imaging (MRI) of the
      brain showed bilateral periventricular confluent high signal intensity. The
      seizure responded to anticonvulsant therapy, and the clinical course was
      characterized by normal development and neurological examination. 

PMID- 24891911
TI  - Garcia-Hafner-Happle syndrome: A case report and review of a rare sub-type of
      epidermal nevus syndrome.
AB  - Garcia-Hafner-Happle syndrome, also known as Fibroblast growth factor receptor 3
      epidermal nevus syndrome, is a new neurocutaneous phenotype, which has been
      identified in 2008 by Garci'a-Vargas et al. The disorder is caused by a mosaic
      R248C mutation of the FGFR3 gene, which is characterized by a keratinocytic
      epidermal nevus, acanthosis nigricans, and neurological abnormalities like
      seizures, intellectual impairment, cortical atrophy, and underdevelopment of
      corpus callosum. The epidermal nevus syndromes represent a group of distinct
      disorders in which an epidermal nevus is associated with abnormalities in other
      organ systems like central nervous system, cardiovascular system, genitourinary
      system, eyes, and bone. Recently, nine well-defined different epidermal nevus
      syndromes (ENSs) have been identified on clinical, histopathologic, and molecular
      basis. We present here the details of a patient with the clinical features and
      skin biopsy findings suggestive of Garcia-Hafner-Happle syndrome. 

PMID- 24891912
TI  - Pontocerebellar hypoplasia type 1 with a milder phenotype in a two-year-old girl.
AB  - The rare association of pontocerebellar hypoplasia with anterior horn cell
      involvement has been classified as pontocerebellar hypoplasia type 1. Its classic
      phenotype is usually severe. However, the pontocerebellar hypoplasia type 1 may
      have wider variability in clinical and radiological features. There may be a
      genetic heterogeneity as well. We described here a young girl with relatively
      milder clinical phenotype with cerebellar atrophy with absent pontine
      involvement, further adding to the clinical phenotype. 

PMID- 24891913
TI  - Giant primary cerebral hydatid cyst: A rare cause of childhood seizure.
AB  - We report a 9-year-old girl who presented with focal seizures, hemiparesis,
      headache, vomiting and bilateral optic atrophy. CT scan revealed a giant solitary
      cyst in the left parietal lobe. Serology and histopathology of the excised cyst
      confirmed the diagnosis of neurohydatidosis which is a rare cause of childhood
      seizure. 

PMID- 24891914
TI  - Pediatric bilateral large concurrent thalamic glioblastoma: An unusual case
      report.
AB  - Bilateral thalamic tumors are rare. Pediatric bilateral thalamic glioblastomas
      are even rarer, only five cases reported in the English literature till date. The
      clinical presentation, natural history, and prognosis of pediatric thalamic
      tumors are still relatively obscure. In this article, we report an 8-year-old
      patient with large bilateral thalamic glioblastomas and briefly discuss its
      clinical presentation, possible modalities of management, and prognosis, in the
      light of available literature. 

PMID- 24891915
TI  - A new clinical feature associated with familial early-onset of dystonic-guttural
      tics: An unusual diagnosis of PANDAS.
AB  - Until today there is a large debate about the existence of PANDAS (pediatric
      autoimmune neuropsychiatric disorders associated with streptococcal infections)
      or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually
      have dramatic, "overnight" onset of symptoms, including motor or vocal tics,
      obsessions, and/or compulsions. In addition to these symptoms, children may also
      have comorbid features of associated disorders. Herein, we report a family with
      an early onset of tics, with exclusively dystonic and guttural tics. All patients
      had a particularly strong excitement trigger. Two of the patients were shown to
      have signs suggestive of PANDAS and all family members were Group A beta
      hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group
      of disorders. We have described a PANDAS variant, in which the family seems to
      share common autoimmune pattern and may be viewed in the large spectrum of
      PANDAS. 

PMID- 24891916
TI  - Recurrent encephalopathy? No I'm a sleeping beauty!
AB  - To describe the clinical presentation of 'Kleine-Levin (sleeping beauty)
      syndrome' in a child, who presented with recurrent episodes consistent with
      encephalopathy, associated with excessive sleepiness, cognitive and behavioural
      disturbance and hyper sexuality. 14 years old boy presented acutely with
      excessive tiredness, sleeping excessively, abnormal behaviour and hypersexuality
      following a viral throat infection. On examination he was sleepy but easily
      arousable. His GCS (15/15) and rest of the neurological examination including
      fundoscopy and other systemic examination was completely unremarkable. All his
      initial investigations including electrolytes, LFTs, CSF, virology screen and MRI
      brain scan were normal. Detailed autoimmune screening was also negative. EEG
      showed non-specific diffuse slowing consistent with encephalopathy. His excessive
      sleepiness gradually improved together with his altered behaviour in about two
      weeks after presentation. Hyper sexuality became more overt during this phase.
      All these symptoms completely disappeared three weeks after his presentation and
      he attended school as before. He was readmitted six weeks later with exactly
      similar presentation and again only positive result being diffuse non-specific
      slowing of EEG. His recovery was also similar and he was completely back to his
      normal self in three weeks time. His recurrent symptoms were consistent with
      'Kleine-Levin syndrome (KLS)' or 'sleeping beauty syndrome'. KLS is a rare
      disorder which mainly affects adolescent males. Common symptoms include
      hypersomnia (100%), cognitive changes (96%), eating disturbances (80%),
      hypersexuality, compulsions, and depressed mood. The syndrome usually lasts for 8
      years, with on an average seven episode of 10 days each recurring every 3.5
      months. It is most frequently precipitated by infections and somnolence decreases
      using stimulants in nearly 40% of cases. 

PMID- 24891917
TI  - Pfeiffer syndrome.

PMID- 24891918
TI  - Baclofen induced coma in an infant.

PMID- 24891919
TI  - A novel case of 'muscle eye brain disease' in an immigrant family in India.

PMID- 24891920
TI  - Traumatic enlargement of an intradiploic cavernous hemangioma.

PMID- 24891921
TI  - Tectal glioma with hydrocephalus presenting with spastic and ataxic
      quadriparesis.

PMID- 24891922
TI  - Likelihood-Based Approach to Gene Set Enrichment Analysis with a Finite Mixture
      Model.
AB  - In this paper, we study a parametric modeling approach to gene set enrichment
      analysis. Existing methods have largely relied on nonparametric approaches
      employing, e.g., categorization, permutation or resampling-based significance
      analysis methods. These methods have proven useful yet might not be powerful. By
      formulating the enrichment analysis into a model comparison problem, we adopt the
      likelihood ratio-based testing approach to assess significance of enrichment.
      Through simulation studies and application to gene expression data, we will
      illustrate the competitive performance of the proposed method.

PMID- 24891923
TI  - DNA methylation of the allergy regulatory gene interferon gamma varies by age,
      sex, and tissue type in asthmatics.
AB  - BACKGROUND: Asthma is associated with allergic sensitization in about half of all
      cases, and asthma phenotypes can vary by age and sex. DNA methylation in the
      promoter of the allergy regulatory gene interferon gamma (IFNgamma) has been
      linked to the maintenance of allergic immune function in human cell and mouse
      models. We hypothesized that IFNgamma promoter methylation at two well-studied,
      key cytosine phosphate guanine (CpG) sites (-186 and -54), may differ by age,
      sex, and airway versus systemic tissue in a cohort of 74 allergic asthmatics.
      RESULTS: After sampling buccal cells, a surrogate for airway epithelial cells,
      and CD4+ lymphocytes, we found that CD4+ lymphocyte methylation was significantly
      higher in children compared to adults at both CpG sites (P <0.01). Buccal cell
      methylation was significantly higher in children at CpG -186 (P = 0.03) but not
      CpG -54 (P = 0.66). Methylation was higher in males compared to females at both
      CpG sites in CD4+ lymphocytes (-186: P <0.01, -54: P = 0.02) but not buccal cells
      (-186: P = 0.14, -54: P = 0.60). In addition, methylation was lower in CD4+
      lymphocytes compared to buccal cells (P <0.01) and neighboring CpG sites were
      strongly correlated in CD4+ lymphocytes (r = 0.84, P <0.01) and weakly correlated
      in buccal cells (r = 0.24, P = 0.04). At CpG -186, there was significant
      correlation between CD4+ lymphocytes and buccal cells (r = 0.24, P = 0.04) but
      not at CpG -54 (r = -0.03, P = 0.78). CONCLUSIONS: These findings highlight
      significant age, sex, and tissue-related differences in IFNgamma promoter
      methylation that further our understanding of methylation in the allergic asthma
      pathway and in the application of biomarkers in clinical research.

PMID- 24891924
TI  - Screen Time at Home and School among Low-Income Children Attending Head Start.
AB  - OBJECTIVE: To describe the patterns of screen viewing at home and school among
      low-income preschool-aged children attending Head Start and identify factors
      associated with high home screen time in this population. Few studies have
      examined both home and classroom screen time, or included computer use as a
      component of screen viewing. METHODS: Participants were 2221 low-income preschool
      aged children in the United States studied in the Head Start Family and Child
      Experiences Survey (FACES) in spring 2007. For 5 categories of screen viewing
      (television, video/DVD, video games, computer games, other computer use), we
      assessed children's typical weekday home (parent-reported) and classroom (teacher
      reported) screen viewing in relation to having a television in the child's
      bedroom and sociodemographic factors. RESULTS: Over half of children (55.7%) had
      a television in their bedroom, and 12.5% had high home screen time (>4
      hours/weekday). Television was the most common category of home screen time, but
      56.6% of children had access to a computer at home and 37.5% had used it on the
      last typical weekday. After adjusting for sociodemographic characteristics,
      children with a television in their bedroom were more likely to have high home
      screen time [odds ratio=2.57 (95% confidence interval: 1.80-3.68)]. Classroom
      screen time consisted almost entirely of computer use; 49.4% of children used a
      classroom computer for >=1 hour/week, and 14.2% played computer games at school
      >=5 hours/week. CONCLUSIONS: In 2007, one in eight low-income children attending
      Head Start had >4 hours/weekday of home screen time, which was associated with
      having a television in the bedroom. In the Head Start classroom, television and
      video viewing were uncommon but computer use was common.

PMID- 24891925
TI  - High-dialysate-glucose-induced oxidative stress and mitochondrial-mediated
      apoptosis in human peritoneal mesothelial cells.
AB  - Human peritoneal mesothelial cells (HPMCs) are a critical component of the
      peritoneal membrane and play a pivotal role in dialysis adequacy. Loss of HPMCs
      can contribute to complications in peritoneal dialysis. Compelling evidence has
      shown that high-dialysate glucose is a key factor causing functional changes and
      cell death in HPMCs. We investigated the mechanism of HPMC apoptosis induced by
      high-dialysate glucose, particularly the role of mitochondria in the maintenance
      of HPMCs. HPMCs were incubated at glucose concentrations of 5 mM, 84 mM, 138 mM,
      and 236 mM. Additionally, N-acetylcysteine (NAC) was used as an antioxidant to
      clarify the mechanism of high-dialysate-glucose-induced apoptosis. Exposing HPMCs
      to high-dialysate glucose resulted in substantial apoptosis with cytochrome c
      release, followed by caspase activation and poly(ADP-ribose) polymerase cleavage.
      High-dialysate glucose induced excessive reactive oxygen species production and
      lipid peroxidation as well as oxidative damage to DNA. Mitochondrial
      fragmentation, multiple mitochondrial DNA deletions, and dissipation of the
      mitochondrial membrane potential were also observed. The mitochondrial
      dysfunction and cell death were suppressed using NAC. These results indicated
      that mitochondrial dysfunction is one of the main causes of high-dialysate
      glucose-induced HPMC apoptosis.

PMID- 24891926
TI  - Role of lipid peroxidation products, plasma total antioxidant status, and Cu-, Zn
      superoxide dismutase activity as biomarkers of oxidative stress in elderly
      prediabetics.
AB  - The relationship between hyperglycemia and oxidative stress in diabetes is well
      known, but the influence of metabolic disturbances recognized as prediabetes, in
      elderly patients especially, awaits for an explanation. METHODS: 52 elderly
      persons (65 years old and older) with no acute or severe chronic disorders were
      assessed: waist circumference (WC), body mass index (BMI), percentage of body fat
      (FAT), and arterial blood pressure. During an oral glucose tolerance test (OGTT)
      fasting (0') and 120-minute (120') glycemia and insulinemia were determined, and
      type 2 diabetics (n = 6) were excluded. Subjects were tested for glycated
      hemoglobin HbA1c, plasma lipids, total antioxidant status (TAS), thiobarbituric
      acid-reacting substances (TBARS), and activity of erythrocyte superoxide
      dismutase (SOD-1). According to OGTT results, patients were classified as
      normoglycemics, (NGT, n = 18) and prediabetics, (PRE, n = 28). RESULTS: Both
      groups did not differ with their lipids, FAT, and TBARS. PRE group had higher WC
      (P < 0.002) and BMI (P < 0.002). Lower SOD-1 activity (P < 0.04) and TAS status
      (P < 0.04) were found in PRE versus NGT group. SIGNIFICANCE: In elderly
      prediabetics, SOD-1 and TAS seem to reflect the first symptoms of oxidative
      stress, while TBARS are later biomarkers of oxidative stress.

PMID- 24891927
TI  - Understanding Drug Resistance in Breast Cancer with Mathematical Oncology.
AB  - Chemotherapy is mainstay of treatment for the majority of patients with breast
      cancer, but results in only 26% of patients with distant metastasis living 5
      years past treatment in the United States, largely due to drug resistance. The
      complexity of drug resistance calls for an integrated approach of mathematical
      modeling and experimental investigation to develop quantitative tools that reveal
      insights into drug resistance mechanisms, predict chemotherapy efficacy, and
      identify novel treatment approaches. This paper reviews recent modeling work for
      understanding cancer drug resistance through the use of computer simulations of
      molecular signaling networks and cancerous tissues, with a particular focus on
      breast cancer. These mathematical models are developed by drawing on current
      advances in molecular biology, physical characterization of tumors, and emerging
      drug delivery methods (e.g., nanotherapeutics). We focus our discussion on
      representative modeling works that have provided quantitative insight into
      chemotherapy resistance in breast cancer and how drug resistance can be overcome
      or minimized to optimize chemotherapy treatment. We also discuss future
      directions of mathematical modeling in understanding drug resistance.

PMID- 24891928
TI  - Gastrointestinal endoscopy in the pregnant woman.
AB  - About 20000 gastrointestinal endoscopies are performed annually in America in
      pregnant women. Gastrointestinal endoscopy during pregnancy raises the critical
      issue of fetal safety in addition to patient safety. Endoscopic medications may
      be potentially abortifacient or teratogenic. Generally, Food and Drug
      Administration category B or C drugs should be used for endoscopy.
      Esophagogastroduodenoscopy (EGD) seems to be relatively safe for both mother and
      fetus based on two retrospective studies of 83 and 60 pregnant patients. The
      diagnostic yield is about 95% when EGD is performed for gastrointestinal
      bleeding. EGD indications during pregnancy include acute gastrointestinal
      bleeding, dysphagia > 1 wk, or endoscopic therapy. Therapeutic EGD is
      experimental due to scant data, but should be strongly considered for urgent
      indications such as active bleeding. One study of 48 sigmoidoscopies performed
      during pregnancy showed relatively favorable fetal outcomes, rare bad fetal
      outcomes, and bad outcomes linked to very sick mothers. Sigmoidoscopy should be
      strongly considered for strong indications, including significant acute lower
      gastrointestinal bleeding, chronic diarrhea, distal colonic stricture, suspected
      inflammatory bowel disease flare, and potential colonic malignancy. Data on
      colonoscopy during pregnancy are limited. One study of 20 pregnant patients
      showed rare poor fetal outcomes. Colonoscopy is generally experimental during
      pregnancy, but can be considered for strong indications: known colonic
      mass/stricture, active lower gastrointestinal bleeding, or colonoscopic therapy.
      Endoscopic retrograde cholangiopancreatography (ERCP) entails fetal risks from
      fetal radiation exposure. ERCP risks to mother and fetus appear to be acceptable
      when performed for ERCP therapy, as demonstrated by analysis of nearly 350 cases
      during pregnancy. Justifiable indications include symptomatic or complicated
      choledocholithiasis, manifested by jaundice, cholangitis, gallstone pancreatitis,
      or dilated choledochus. ERCP should be performed by an expert endoscopist, with
      informed consent about fetal radiation risks, minimizing fetal radiation
      exposure, and using an attending anesthesiologist. Endoscopy is likely most safe
      during the second trimester of pregnancy. 

PMID- 24891929
TI  - Update on gastric varices.
AB  - Although less common than oesophageal variceal haemorrhage, gastric variceal
      bleeding remains a serious complication of portal hypertension, with a high
      associated mortality. In this review we provide an update on the aetiology,
      classification and management of gastric varices, including acute bleeding,
      prevention of rebleeding and primary prophylaxis. We describe the optimum
      management strategies for gastric varices including drug, endoscopic and
      radiological therapies, focusing on recent published evidence. 

PMID- 24891930
TI  - Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable
      bowel syndrome.
AB  - AIM: To study the different endocrine cell types in the oxyntic mucosa of
      patients with irritable bowel syndrome (IBS). METHODS: Seventy-six patients with
      IBS were included in the study (62 females and 14 males; mean age 32 years, range
      18-55 years), of which 40 also fulfilled the Rome III criteria for functional
      dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant
      symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29
      had constipation as the predominant symptom (IBS-C). Forty-three age and sex
      matched healthy volunteers without any gastrointestinal complaints served as
      controls. The patients were asked to complete the Birmingham IBS symptom
      questionnaire. Both the patients and controls underwent a standard gastroscopy,
      during which three biopsy samples were taken from the corpus. Sections from these
      biopsy samples were immunostained using the avidin-biotin complex (ABC) method,
      for ghrelin, serotonin, somatostatin and histamine. The densities of these cell
      types and immunoreactivity intensities were quantified using computerized image
      analysis with Olympus cellSens imaging software (version 1.7). RESULTS: The
      densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C
      groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and
      126 (0, 262) cells/mm(2), respectively. There was a significant difference
      between the tested groups (P < 0.0001). Dunn's multiple comparison test showed
      that the ghrelin cell density was significantly higher in IBS-D and lower in IBS
      C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell
      density in patients with both IBS and FDP was 489 (130, 966), and in those with
      IBS only 490 (130, 956). There was no statistical significant difference between
      these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not
      differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham
      IBS symptom questionnaire was significantly positively correlated with ghrelin
      cell density (r = 0.65; P < 0.0001) and significantly inversely correlated with
      that of constipation (r = 90.69; P < 0.0001). The densities of the serotonin
      cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46)
      cells/mm(2) in the control, IBS-total, IBS-D, IBS-M and IBS-C groups,
      respectively. A statistically significant difference was found between the tested
      groups (P < 0.0001). Posttest revealed that serotonin cell density was
      significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and
      0.004, respectively), but did not differ in the IBS-total and IBS-M groups from
      that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in
      patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65
      (25, 123). There was no statistically significant difference between these 2
      groups of patients (P = 1). The immunoreactivity intensity of serotonin did not
      differ significantly between any of the groups (P = 0.0.9). The serotonin cell
      density was significantly positively correlated with the diarrhea score of the
      Birmingham IBS symptom questionnaire (r = 0.56; P < 0.0001) and significantly
      inversely correlated with that of constipation (r = 0.51; P < 0.0001). The
      densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80),
      46 (0, 103) and 206 (194, 314) cells/mm(2) in the control, IBS-total, IBS-D, IBS
      M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically
      significant difference between the controls and the IBS subgroups (P < 0.0001).
      The density of somatostatin cells was significantly lower in the IBS-D and IBS-M
      groups but higher in IBS-C patients than in the controls (P < 0.01, P = 0.02, and
      P = 0.0008, respectively). The somatostatin cell density in patients with both
      IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no
      statistically significant difference between these 2 groups of patients (P =
      0.6). There was no significant difference in somatostatin immunoreactivity
      intensity between the controls. The diarrhea score of the Birmingham IBS symptom
      questionnaire was inversely correlated with somatostatin cell density (r = 0.38;
      P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P
      < 0.0001). CONCLUSION: The finding of abnormal endocrine cells in the oxyntic
      mucosa shows that the endocrine cell disturbances in IBS are not restricted to
      the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin
      in the oxyntic mucosa of the stomach may play an important role in the changing
      stool habits in IBS through their effects on intestinal motility.

PMID- 24891931
TI  - Withdrawal time in excellent or very poor bowel preparation qualities.
AB  - AIM: To evaluate association(s) between withdrawal time and polyp detection in
      various bowel preparation qualities. METHODS: Retrospective cohort analysis of
      screening colonoscopies performed between January 2005 and June 2011 for patients
      with average risk of colorectal cancer. Exclusion criteria included patients with
      a personal history of adenomatous polyps or colon cancer, prior colonic
      resection, significant family history of colorectal cancer, screening colonoscopy
      after other abnormal screening tests such as flexible sigmoidoscopy or barium
      enema, and screening colonoscopies during in-patient care. All procedures were
      performed or directly supervised by gastroenterologists. Main measurements were
      number of colonic segments with polyps and total number of colonic polyps.
      RESULTS: Multivariate analysis of 8331 colonoscopies showed longer withdrawal
      time was associated with more colonic segments with polyps in good (adjusted OR =
      1.16; 95%CI: 1.13-1.19), fair (OR = 1.13; 95%CI: 1.10-1.17), and poor (OR = 1.18;
      95%CI: 1.11-1.26) bowel preparation qualities. A higher number of total polyps
      was associated with longer withdrawal time in good (OR = 1.15; 95%CI: 1.13-1.18),
      fair (OR = 1.13; 95%CI: 1.10-1.16), and poor (OR = 1.20; 95%CI: 1.13-1.29) bowel
      preparation qualities. Longer withdrawal time was not associated with more
      colonic segments with polyps or greater number of colonic polyps in bowel
      preparations with excellent (OR = 1.07, 95%CI: 0.99-1.26; OR = 1.11, 95%CI: 0.99
      1.24, respectively) and very poor (OR = 1.02, 95%CI: 0.99-1.12; OR = 1.05, 95%CI:
      0.99-1.10, respectively) qualities. CONCLUSION: Longer withdrawal time is not
      associated with higher polyp number detected in colonoscopies with excellent or
      very poor bowel preparation quality.

PMID- 24891932
TI  - Using motion capture to assess colonoscopy experience level.
AB  - AIM: To study technical skills of colonoscopists using a Microsoft KinectTM for
      motion analysis to develop a tool to guide colonoscopy education. RESULTS: Ten
      experienced endoscopists (gastroenterologists, n = 2; colorectal surgeons, n = 8)
      and 11 novices participated in the study. A Microsoft KinectTM recorded the
      movements of the participants during the insertion of the colonoscope. We used a
      modified script from Microsoft to record skeletal data. Data were saved and later
      transferred to MatLab for analysis and the calculation of statistics. The test
      was performed on a physical model, specifically the "Kagaku Colonoscope Training
      Model" (Kyoto Kagaku Co. Ltd, Kyoto, Japan). After the introduction to the scope
      and colonoscopy model, the test was performed. Seven metrics were analyzed to
      find discriminative motion patterns between the novice and experienced
      endoscopists: hand distance from gurney, number of times the right hand was used
      to control the small wheel of the colonoscope, angulation of elbows, position of
      hands in relation to body posture, angulation of body posture in relation to the
      anus, mean distance between the hands and percentage of time the hands were
      approximated to each other. RESULTS: Four of the seven metrics showed
      discriminatory ability: mean distance between hands [45 cm for experienced
      endoscopists (SD 2) vs 37 cm for novice endoscopists (SD 6)], percentage of time
      in which the two hands were within 25 cm of each other [5% for experienced
      endoscopists (SD 4) vs 12% for novice endoscopists (SD 9)], the level of the
      right hand below the sighting line (z-axis) (25 cm for experienced endoscopists
      vs 36 cm for novice endoscopists, P < 0.05) and the level of the left hand below
      the z-axis (6 cm for experienced endoscopists vs 15 cm for novice endoscopists, P
      < 0.05). By plotting the distributions of the percentages for each group, we
      determined the best discriminatory value between the groups. A pass score was set
      at the intersection of the distributions, and the consequences of the standard
      were explored for each test. By using the contrasting group method, we showed a
      discriminatory value of Z = 1.51 to be the pass/fail value of the data showing
      discriminatory ability. The pass score allowed all ten experienced endoscopists
      as well as five novice endoscopists to pass the test. CONCLUSION: Identified
      metrics can be used to discriminate between experienced and novice endoscopists
      and to provide non-biased feedback. Whether it is possible to use this tool to
      train novices in a clinical setting requires further study.

PMID- 24891933
TI  - Early precut sphincterotomy and the risk of endoscopic retrograde
      cholangiopancreatography related complications: An updated meta-analysis.
AB  - AIM: To study the cannulation and complication rates of early pre-cut
      sphincterotomy vs persistent attempts at cannulation by standard approach.
      METHODS: Systematic search of PubMed, EMBASE, Web of Science, and the Cochrane
      Library for relevant studies published up to February 2013. The main outcome
      measurements were cannulation rates and post-endoscopic retrograde
      cholangiopancreatography (ERCP) complications. A comprehensive systematic search
      of the Cochrane library, PubMed, Google scholar, Scopus, National Institutes of
      Health, meta-register of controlled trials and published proceedings from major
      Gastroenterology journals and meetings until February 2013 was conducted using
      keywords. All Prospective randomized controlled trials (RCT) studies which met
      our inclusion criteria were included in the analysis. Prospective non-randomized
      studies and retrospective studies were excluded from our meta-analysis. The main
      outcomes of interest were post-ERCP pancreatitis, overall complication rates
      including cholangitis, ERCP-related bleeding, perforation and cannulation success
      rates. RESULTS: Seven RCTs with a total of 1039 patients were included in the
      meta-analysis based on selection criteria. The overall cannulation rate was 90%
      in the pre-cut sphincterotomy vs 86.3% in the persistent attempts group (OR =
      1.98; 95%CI: 0.70-5.65). The risk of post-ERCP pancreatitis (PEP) was not
      different between the two groups (3.9% in the pre-cut sphincterotomy vs 6.1% in
      the persistent attempts group, OR = 0.58, 95%CI: 0.32-1.05). Similarly, there was
      no statistically significant difference between the groups for overall
      complication rate including PEP, cholangitis, bleeding, and perforation (6.2% vs
      6.9%, OR = 0.85, 95%CI: 0.51-1.41). CONCLUSION: This meta-analysis suggests that
      pre-cut sphincterotomy and persistent attempts at cannulation are comparable in
      terms of overall complication rates. Early pre-cut implementation does not
      increase PEP complications.

PMID- 24891934
TI  - Systematic review of oncological outcomes following laparoscopic vs open total
      mesorectal excision.
AB  - AIM: To systematically analyze the randomized trials comparing the oncological
      and clinical effectiveness of laparoscopic total mesorectal excision (LTME) vs
      open total mesorectal excision (OTME) in the management of rectal cancer.
      METHODS: Published randomized, controlled trials comparing the oncological and
      clinical effectiveness of LTME vs OTME in the management of rectal cancer were
      retrieved from the standard electronic medical databases. The data of included
      randomized, controlled trials was extracted and then analyzed according to the
      principles of meta-analysis using RevMan((r)) statistical software. The combined
      outcome of the binary variables was expressed as odds ratio (OR) and the combined
      outcome of the continuous variables was presented in the form of standardized
      mean difference (SMD). RESULTS: Data from eleven randomized, controlled trials on
      2143 patients were retrieved from the electronic databases. There was a trend
      towards the higher risk of surgical site infection (OR = 0.66; 95%CI: 0.44-1.00;
      z = 1.94; P < 0.05), higher risk of incomplete total mesorectal resection (OR =
      0.62; 95%CI: 0.43-0.91; z = 2.49; P < 0.01) and prolonged length of hospital stay
      (SMD, -1.59; 95%CI: -0.86--0.25; z = 4.22; P < 0.00001) following OTME. However,
      the oncological outcomes like number of harvested lymph nodes, tumour recurrence
      and risk of positive resection margins were statistically similar in both groups.
      In addition, the clinical outcomes such as operative complications, anastomotic
      leak and all-cause mortality were comparable between both approaches of
      mesorectal excision. CONCLUSION: LTME appears to have clinically and
      oncologically measurable advantages over OTME in patients with primary rectal
      cancer in both short term and long term follow ups.

PMID- 24891936
TI  - Antibiotic usage in 2013 on a dairy CAFO in NY State, USA.
AB  - Antimicrobial resistance is threatening humans and animals worldwide. Biosecurity
      and 1-year usage of antibiotics on a dairy concentrated animal feeding operation
      (CAFO) in NY State, USA, were mapped: how much antibiotics were used, for what
      purpose, and whether any decrease could be warranted. Approximately 493 kg
      antibiotics was used, of which 376 kg was ionophores (monensin and lasalocides),
      79 kg penicillin, 16.5 kg lincosamides, 8.0 kg aminoglycosides, 7.7 kg
      sulfamides, 3.4 kg cephalosporin, 2 kg macrolides, 0.7 kg amphenicols, and 0.1 kg
      fluoroquinolones. Usage reduction by 84% was realistic without compromising the
      animal welfare. Further reduction could be possible by improving the biosecurity
      and by utilizing antibiotic sensitivity testing. 

PMID- 24891937
TI  - The quality control theory of aging.
AB  - The quality control (QC) theory of aging is based on the concept that aging is
      the result of a reduction in QC of cellular systems designed to maintain lifelong
      homeostasis. Four QC systems associated with aging are 1) inadequate protein
      processing in a distressed endoplasmic reticulum (ER); 2) histone deacetylase
      (HDAC) processing of genomic histones and gene silencing; 3) suppressed AMPK
      nutrient sensing with inefficient energy utilization and excessive fat
      accumulation; and 4) beta-adrenergic receptor (BAR) signaling and environmental
      and emotional stress. Reprogramming these systems to maintain efficiency and
      prevent aging would be a rational strategy for increased lifespan and improved
      health. The QC theory can be tested with a pharmacological approach using three
      well-known and safe, FDA-approved drugs: 1) phenyl butyric acid, a chemical
      chaperone that enhances ER function and is also an HDAC inhibitor, 2) metformin,
      which activates AMPK and is used to treat type 2 diabetes, and 3) propranolol, a
      beta blocker which inhibits BAR signaling and is used to treat hypertension and
      anxiety. A critical aspect of the QC theory, then, is that aging is associated
      with multiple cellular systems that can be targeted with drug combinations more
      effectively than with single drugs. But more importantly, these drug combinations
      will effectively prevent, delay, or reverse chronic diseases of aging that impose
      such a tremendous health burden on our society. 

PMID- 24891935
TI  - Alcohol-induced hypertension: Mechanism and prevention.
AB  - Epidemiological, preclinical and clinical studies established the association
      between high alcohol consumption and hypertension. However the mechanism through
      which alcohol raises blood pressure remains elusive. Several possible mechanisms
      have been proposed such as an imbalance of the central nervous system, impairment
      of the baroreceptors, enhanced sympathetic activity, stimulation of the renin
      angiotensin-aldosterone system, increased cortisol levels, increased vascular
      reactivity due to increase in intracellular calcium levels, stimulation of the
      endothelium to release vasoconstrictors and loss of relaxation due to
      inflammation and oxidative injury of the endothelium leading to inhibition of
      endothelium-dependent nitric oxide production. Loss of relaxation due to
      inflammation and oxidative injury of the endothelium by angiotensin II leading to
      inhibition of endothelium-dependent nitric oxide production is the major
      contributors of the alcohol-induced hypertension. For the prevention of alcohol
      induced hypertension is to reduce the amount of alcohol intake. Physical
      conditioning/exercise training is one of the most important strategies to
      prevent/treat chronic alcohol-induced hypertension on physiological basis. The
      efficacious pharmacologic treatment includes the angiotensin-converting enzyme
      (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs) which have
      antioxidant activity and calcium channel blockers. The most effective prevention
      and treatment of alcohol-induced hypertension is physical exercise and the use of
      ACE inhibitors or ARBs in the clinic. 

PMID- 24891938
TI  - Antihypertensive therapy initiation in the elderly increases hip fracture risk.

PMID- 24891939
TI  - PPARbeta/delta and its role in Wnt signaling and bone turnover.

PMID- 24891940
TI  - IGH amplification in patients with B cell lymphoma unclassifiable, with features
      intermediate between diffuse large B cell lymphoma and Burkitt's lymphoma.
AB  - B cell lymphoma, unclassifiable, with features intermediate between diffuse large
      B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL) (B-UNC/BL/DLBCL) is a new
      category of tumors that have features resembling both DLBCL and BL. These tumors
      have large and medium sized cells with greater irregularity of nuclei and more
      prominent nucleoli than BL. Approximately 35% to 50% have C-MYC rearrangements,
      although half are non-immunoglobulin variants. We identified six cases of B
      UNC/BL/DLBCL with low-level IGH amplification. Four patients died with a median
      survival of 7 months (range, 6-20). In conclusion, to our knowledge low-level IGH
      amplification has not been previously described and should be evaluated for in
      this patient population. 

PMID- 24891941
TI  - Paraneoplastic hypoglycemia in a patient with a malignant solitary fibrous tumor.
AB  - Hypoglycemia is a common medical emergency. It is the most frequent complication
      induced by anti-diabetic treatment. However, it can be observed in other
      conditions unrelated to diabetes such as insulinoma, autoimmune disorders, and
      neoplasia. Herein, we report the case of a rare cause of severe and recurrent
      hypoglycemia in a 77-year-old woman with a malignant solitary fibrous tumor
      (MSFT). A 77-year-old woman was admitted to the emergency department for loss of
      consciousness induced by severe hypoglycemia. Her standard laboratory findings
      were unremarkable. HbA1c, albumin, renal, liver, thyroid, and adrenal function
      tests were normal. Cerebral CT scan was also normal. At the time of confirmed
      hypoglycemia, the serum level of insulin and C-peptide was low. On the basis of
      the past medical history and the absence of other comment etiologies, a
      paraneoplastic cause was suspected. Thus, the diagnosis of a non-islet cell tumor
      induced hypoglycemia (NICTH) was established by the presence of incompletely
      processed precursors of IGF2 (big IGF2) in plasma electrophoresis. However, the
      IGF1 level was low. Therapy with corticosteroids improved hypoglycemia and
      clinical symptoms. NICTH is a rare cause of hypoglycemia. It should be considered
      in patients with mesenchymal or malignant epithelial tumors suffering from
      recurrent episodes of hypoglycemia. The diagnosis will be established in the case
      of low serum insulin concentrations and elevated levels of big IGF2. Treatment
      with corticosteroids, GH, or both can improve hypoglycemic symptoms and restore
      plasma glucose to normal levels. LEARNING POINTS: NICTH is a very rare condition
      that should be considered in patients known to have mesenchymal or malignant
      epithelial tumors and suffering from recurrent episodes of hypoglycemia.The
      diagnosis of an NICTH is established on the basis of the hypoinsulinemic
      hypoglycemia, the MSFT history, and the presence of paraneoplastic secretion of
      IGF1 or an immature form of IGF2.Treatment with corticosteroids, GH, or both can
      improve hypoglycemic symptoms and restore plasma glucose to normal levels in
      NICTH.

PMID- 24891942
TI  - Swimming performances in long distance open-water events with and without
      wetsuit.
AB  - BACKGROUND: Existing literature showed improved swimming performances for
      swimmers wearing wetsuits competing under standardized conditions in races held
      in pools on short to middle distances. Data about the influence of wetsuits on
      swimming performances in long and ultra-long open-water swimming races are
      missing. It is unknown whether the benefit of wearing wetsuits is comparable in
      men and women. The aim of this study was to investigate the influence of wearing
      a wetsuit on open-water swimming performances at the 26.4 km 'Marathon Swim in
      Lake Zurich' in Lake Zurich, Switzerland, and the 3.8 km Lake Ontario Swim Team
      Race (LOST-Race) in Lake Ontario, Canada. METHODS: Race times of the fastest
      female and male swimmers competing with and without wetsuit were compared using
      multi-level regression analyses and analysis of variance. RESULTS: In the
      'Marathon Swim' in Lake Zurich, wearing a wetsuit had no effect on race time
      regarding the gender where athletes wearing a wetsuit were not faster than
      athletes without wetsuit. However, the ten fastest men wearing a wetsuit (410.6
      +/- 26.7 min) were faster (32.7%, p < 0.01) than the ten fastest women without
      wetsuit (544.9 +/- 81.3 min). In the 'LOST-Race', the top ten men wearing a
      wetsuit (51.7 +/- 2.5 min) were faster (13.2%, p < 0.01) than the top ten women
      wearing a wetsuit (58.5 +/- 3.2 min). Additionally, the top ten men without
      wetsuit (52.1 +/- 2.4 min) were faster (19.6%, p < 0.01) than the top ten women
      without wetsuit (62.3 +/- 2.5 min). The top ten women wearing a wetsuit (58.5 +/-
      3.2 min) were faster (6.5%, p < 0.01) than top ten women without a wetsuit (62.3
      +/- 25 min). CONCLUSIONS: These results suggest that wearing a wetsuit had a
      positive influence on swimming speed for both women and men but the benefit of
      the use of wetsuits seemed to depend on additional factors (i.e. race distance).
      Women seemed to benefit more from wearing wetsuits than men in longer open-water
      ultra-distance swimming races.

PMID- 24891943
TI  - High-resolution in vivo imaging of regimes of laser damage to the primate retina.
AB  - Purpose. To investigate fundamental mechanisms of regimes of laser induced damage
      to the retina and the morphological changes associated with the damage response.
      Methods. Varying grades of photothermal, photochemical, and photomechanical
      retinal laser damage were produced in eyes of eight cynomolgus monkeys. An
      adaptive optics confocal scanning laser ophthalmoscope and spectral domain
      optical coherence tomographer were combined to simultaneously collect
      complementary in vivo images of retinal laser damage during and following
      exposure. Baseline color fundus photography was performed to complement high
      resolution imaging. Monkeys were perfused with 10% buffered formalin and eyes
      were enucleated for histological analysis. Results. Laser energies for visible
      retinal damage in this study were consistent with previously reported damage
      thresholds. Lesions were identified in OCT images that were not visible in direct
      ophthalmoscopic examination or fundus photos. Unique diagnostic characteristics,
      specific to each damage regime, were identified and associated with shape and
      localization of lesions to specific retinal layers. Previously undocumented
      retinal healing response to blue continuous wave laser exposure was recorded
      through a novel experimental methodology. Conclusion. This study revealed
      increased sensitivity of lesion detection and improved specificity to the laser
      of origin utilizing high-resolution imaging when compared to traditional
      ophthalmic imaging techniques in the retina. 

PMID- 24891944
TI  - Gender and uveitis in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS), a demyelinating disease of the central nervous system,
      is more commonly seen in women. It has been associated with both anterior and
      intermediate uveitis as well as retinal vasculitis. Ocular inflammation may
      develop concurrent with, prior to, or after the development of neurologic signs
      and symptoms. Patients with MS have an approximately 1% chance of developing
      intraocular inflammation. Patients with intermediate uveitis have an 8-12% risk
      of being diagnosed with MS. This risk is higher in females and in those with
      bilateral disease. This should be kept in mind when evaluating patients with
      uveitis, particularly in those patients for whom TNF inhibitor therapy is being
      considered, as these agents may worsen demyelinating disease. 

PMID- 24891945
TI  - Excimer laser phototherapeutic keratectomy for the treatment of clinically
      presumed fungal keratitis.
AB  - This retrospective study was to evaluate treatment outcomes of excimer laser
      phototherapeutic keratectomy (PTK) for clinically presumed fungal keratitis.
      Forty-seven eyes of 47 consecutive patients underwent manual superficial
      debridement and PTK. All corneal lesions were located in the anterior stroma and
      were resistant to medication therapy for at least one week. Data were collected
      by a retrospective chart review with at least six months of follow-up data
      available. After PTK, infected corneal lesions were completely removed and the
      clinical symptoms resolved in 41 cases (87.2%). The mean ablation depth was
      114.39 +/- 45.51  MU m and diameter of ablation was 4.06 +/- 1.07 mm. The mean
      time for healing of the epithelial defect was 8.8 +/- 5.6 days. Thirty-four eyes
      (82.9%) showed an improvement in best spectacle-corrected visual acuity of two or
      more lines. PTK complications included mild to moderate corneal haze, hyperopic
      shift, irregular astigmatism, and thinning cornea. Six eyes (12.8%) still showed
      progressed infection, and conjunctival flap covering, amniotic membrane
      transplantation, or penetrating keratoplasty were given. PTK is a valuable
      therapeutic alternative for superficial infectious keratitis. It can effectively
      eradicate lesions, hasten reepithelialization, and restore and preserve useful
      visual function. However, the selection of surgery candidates should be conducted
      carefully. 

PMID- 24891946
TI  - Binge eating behavior and weight loss maintenance over a 2-year period.
AB  - OBJECTIVE: To investigate the relationship between binge eating behavior and
      weight loss maintenance over a two-year period in adults. DESIGN: Secondary data
      analysis using the Keep It Off study, a randomized trial evaluating an
      intervention to promote weight loss maintenance. PARTICIPANTS: 419 men and women
      (ages: 20 to 70 y; BMI: 20-44 kg/m2) who had intentionally lost >=10% of their
      weight during the previous year. MEASUREMENTS: Body weight was measured and binge
      eating behavior over the past 6 months was reported at baseline, 12 months and 24
      months. Height was measured at baseline. RESULTS: Prevalence of binge eating at
      baseline was 19.4% (n = 76). Prevalence of binge eating at any time point was
      30.1% (n = 126). Although rate of weight regain did not differ significantly
      between those who did or did not report binge eating at baseline, binge eating
      behavior across the study period (additive value of presence or absence at each
      time point) was significantly associated with different rates of weight regain.
      CONCLUSION: Tailoring weight loss maintenance interventions to address binge
      eating behavior is warranted given the prevalence and the different rates of
      weight regain experienced by those reporting this behavior.

PMID- 24891947
TI  - Histological and clinical characteristics of patients with chronic hepatitis C
      and persistently normal alanine aminotransferase levels.
AB  - Patients with chronic hepatitis C virus (HCV) infection and persistently normal
      alanine aminotransferase (PNALT) are generally described to have mild liver
      disease. The aim of this study was to compare clinical and histological features
      in HCV-infected patients with PNALT and elevated ALT. Patients presenting to the
      University of Illinois Medical Center, Chicago, who had biopsy proven HCV, an ALT
      measurement at the time of liver biopsy, at least one additional ALT measurement
      over the next 12 months, and liver biopsy slides available for review were
      identified. PNALT was defined as ALT <= 30 on at least 2 different occasions over
      12 months. Of 1200 patients with HCV, 243 met the study criteria. 13% (32/243) of
      patients had PNALT while 87% (211/243) had elevated ALT. Significantly more
      patients with PNALT had advanced fibrosis (F3 and F4) compared to those with
      elevated ALT (P = 0.007). There was no significant difference in the histology
      activity index score as well as mean inflammatory score between the two groups.
      In conclusion, in a well-characterized cohort of patients at a tertiary medical
      center, PNALT did not distinguish patients with mild liver disease. 

PMID- 24891948
TI  - Treatment outcome of tuberculosis patients at enfraz health center, northwest
      ethiopia: a five-year retrospective study.
AB  - Objectives. The aim of this study was to assess treatment outcome and associated
      risk factors among TB patients registered for anti-TB treatment at Enfraz health
      center, northwest Ethiopia. Methods. A five-year retrospective data (2007-2011)
      of tuberculosis patients (n = 417) registered for anti-TB treatment at Enfraz
      health center, northwest Ethiopia, were reviewed. Tuberculosis outcomes were
      following the WHO guidelines. Data were entered and analyzed using SPSS version
      20. Results. Among 417 study participants, 95 (22.8%), 141 (33.8%), and 181
      (43.4%) were smear-positive, smear-negative, and extrapulmonary tuberculosis
      patients, respectively. Of the 417 study participants, 206 (49.4%) were tested
      for HIV. The TB-HIV coinfection was 24/206 (11.7%). Seventeen study participants
      (4.2%) were transferred to other health facilities. Among the 400 study
      participants, 379 (94.8%) had successful treatment outcome (302 treatment
      completed and 77 cured). The overall death, default, and failure rates were 3.4%,
      0.5%, and 1.2%, respectively. There was no significant association between sex,
      age, residence, type of TB, HIV status, and successful TB treatment outcome.
      Conclusion. Treatment outcome of patients who attended their anti-TB treatment at
      Enfraz health center was successful. Therefore, this treatment success rate
      should be maintained and strengthened to achieve the millennium development goal.

PMID- 24891949
TI  - Pathogenesis of painful diabetic neuropathy.
AB  - The prevalence of diabetes is rising globally and, as a result, its associated
      complications are also rising. Painful diabetic neuropathy (PDN) is a well-known
      complication of diabetes and the most common cause of all neuropathic pain. About
      one-third of all diabetes patients suffer from PDN. It has a huge effect on a
      person's daily life, both physically and mentally. Despite huge advances in
      diabetes and neurology, the exact mechanism of pain causation in PDN is still not
      clear. The origin of pain could be in the peripheral nerves of the central
      nervous system. In this review, we discuss various possible mechanisms of the
      pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering
      the physiology of peripheral nerves. We also describe central mechanisms of pain.

PMID- 24891950
TI  - Clinical characteristics, patient-reported outcomes, and previous therapeutic
      management of patients with uncontrolled neuropathic pain referred to pain
      clinics.
AB  - Background. The aim of this report was to evaluate the clinical profile and
      previous management of patients with uncontrolled neuropathic pain who were
      referred to pain clinics. Methods. We included adult patients with uncontrolled
      pain who had a score of >=4 in the DN4 questionnaire. In addition to
      sociodemographic and clinical data, we evaluated pain levels using a visual
      analog scale as well as anxiety, depression, sleep, disability, and treatment
      satisfaction employing validated tools. Results. A total of 755 patients were
      included in the study. The patients were predominantly referred to pain clinics
      by traumatologists (34.3%) and primary care physicians (16.7%). The most common
      diagnoses were radiculopathy (43%) and pain of oncological origin (14.3%). The
      major cause for uncontrolled pain was suboptimal treatment (88%). Fifty-three
      percent of the patients were depressed, 43% had clinical anxiety, 50% rated their
      overall health as bad or very bad, and 45% noted that their disease was severely
      or extremely interfering with their daily activities. Conclusions. Our results
      showed that uncontrolled neuropathic pain is a common phenomenon among the
      specialties that address these clinical entities and, regardless of its etiology,
      uncontrolled pain is associated with a dramatic impact on patient well-being. 

PMID- 24891951
TI  - Anatomical variations of the circulus arteriosus in cadaveric human brains.
AB  - Objective. Circulus arteriosus/circle of Willis (CW) is a polygonal anastomotic
      channel at the base of the brain which unites the internal carotid and
      vertebrobasilar system. It maintains the steady and constant supply to the brain.
      The variations of CW are seen often. The Aim of the present work is to find out
      the percentage of normal pattern of CW, and the frequency of variations of the CW
      and to study the morphological and morphometric aspects of all components of CW.
      Methods. Circulus arteriosus of 150 formalin preserved brains were dissected.
      Dimensions of all the components forming circles were measured. Variations of all
      the segments were noted and well photographed. The variations such as aplasia,
      hypoplasia, duplication, fenestrations, and difference in dimensions with
      opposite segments were noted. The data collected in the study was analyzed.
      Results. Twenty-one different types of CW were found in the present study. Normal
      and complete CW was found in 60%. CW with gross morphological variations was seen
      in 40%. Maximum variations were seen in the PCoA followed by the ACoA in 50% and
      40%, respectively. Conclusion. As it confirms high percentage of variations, all
      surgical interventions should be preceded by angiography. Awareness of these
      anatomical variations is important in neurovascular procedures. 

PMID- 24891952
TI  - Multiple sclerosis: evaluation of purine nucleotide metabolism in central nervous
      system in association with serum levels of selected fat-soluble antioxidants.
AB  - In the pathogenesis of demyelinating diseases including multiple sclerosis (MS)
      an important role is played by oxidative stress. Increased energy requirements
      during remyelination of axons and mitochondria failure is one of the causes of
      axonal degeneration and disability in MS. In this context, we analyzed to what
      extent the increase in purine catabolism is associated with selected blood
      lipophilic antioxidants and if there is any association with alterations in serum
      levels of coenzyme Q10. Blood serum and cerebrospinal fluid (CSF) samples from 42
      patients with diagnosed MS and 34 noninflammatory neurologic patients (control
      group) were analyzed. Compared to control group, MS patients had significantly
      elevated values of all purine nucleotide metabolites, except adenosine. Serum
      lipophilic antioxidants gamma -tocopherol, beta -carotene, and coenzyme Q10 for
      the vast majority of MS patients were deficient or moved within the border of
      lower physiological values. Serum levels of TBARS, marker of lipid peroxidation,
      were increased by 81% in the MS patients. The results indicate that the deficit
      of lipophilic antioxidants in blood of MS patients may have a negative impact on
      bioenergetics of reparative remyelinating processes and promote
      neurodegeneration. 

PMID- 24891953
TI  - Exploring Factors Affecting Emergency Medical Services Staffs' Decision about
      Transporting Medical Patients to Medical Facilities.
AB  - Transfer of patients in medical emergency situations is one of the most important
      missions of emergency medical service (EMS) staffs. So this study was performed
      to explore affecting factors in EMS staffs' decision during transporting of
      patients in medical situations to medical facilities. The participants in this
      qualitative study consisted of 18 EMS staffs working in prehospital care
      facilities in Tehran, Iran. Data were gathered through semistructured interviews.
      The data were analyzed using a content analysis approach. The data analysis
      revealed the following theme: "degree of perceived risk in EMS staffs and their
      patients." This theme consisted of two main categories: (1) patient's condition'
      and (2) the context of the EMS mission'. The patent's condition category emerged
      from "physical health statuses," "socioeconomic statuses," and "cultural
      background" subcategories. The context of the EMS mission also emerged from two
      subcategories of "characteristics of the mission" and EMS staffs
      characteristics'. EMS system managers can consider adequate technical,
      informational, financial, educational, and emotional supports to facilitate the
      decision making of their staffs. Also, development of an effective and user
      friendly checklist and scoring system was recommended for quick and easy
      recognition of patients' needs for transportation in a prehospital situation. 

PMID- 24891955
TI  - Squamous cell carcinomas of the skin explore angiogenesis-independent mechanisms
      of tumour vascularization.
AB  - Aims. To evaluate the vascularization in basal cell carcinomas (BCCs) and
      squamous cell carcinomas (SCCs) of the skin. Methods. We performed CD31 (i.e.,
      panendothelial marker) and CD105 (i.e., proliferating endothelium marker)
      immunostaining on samples of 70 SCCs and 70 BCCs of the skin. We evaluated the
      relative blood vessel area using the Chalkley counting method in each histologic
      subtype of these tumours. We calculated the degree of proliferation of blood
      vessel endothelium dividing CD105-Chalkley score by CD31-Chalkley score. Results.
      We found significantly higher peritumoral and intratumoral blood vessel area in
      SCC when compared to BCC (both with CD31 and CD105). Chalkley counts differed
      significantly between groups with different BCC histologic subtypes and SCC with
      different grade of differentiation. Surprisingly, the degree of proliferation of
      blood vessel endothelium was higher in BCC when compared to SCC. Conclusions.
      While SCC exhibited significantly higher intratumoral and peritumoral blood
      vessel areas compared to BCC, the relatively low rate of proliferating
      endothelium in this tumour type suggests the existence of endothelial-sprouting
      independent mechanisms of vascularization in SCC. 

PMID- 24891956
TI  - Quality of Life in Patients with Focal Hyperhidrosis before and after Treatment
      with Botulinum Toxin A.
AB  - The aim of this study is to assess the effectiveness of treatment with BTX-A in
      quality of life of patients suffering from primary focal hyperhidrosis. Materials
      and Methods. A total of 119 patients (62 females and 57 males) between 18 and 65
      years suffering from moderate to severe focal hyperhidrosis were treated with BTX
      A. Thirty-nine patients suffered from axillary hyperhidrosis, 47 patients from
      palmar hyperhidrosis, 12 patients from plantar hyperhidrosis, and 21 patients
      from palmar and plantar hyperhidrosis. A baseline and posttreated examination of
      patients 6 months after BTX-A is included. The Hyperhidrosis Disease Severity
      Scale (HDSS) was chosen to assess the disease severity and the modified
      Dermatology Life Quality Index was used (DLQI) to assess the quality of life.
      Results. Quality of life showed a significant improvement after treatment with
      BTX-A. The total DLQI score resulted significantly lower than the basal value (P
      < 0.0001). The seriousness of hyperhidrosis significantly decreased after the
      treatment (P < 0.0001). In addition, there was notable difference between the
      posttreatment DLQI scores and pretreatment severity of hyperhidrosis by sex.
      Conclusions. Treatment with BTX-A led to the reduction of disease severity and
      improvement of quality of life, while it is a safe, easy to use method with
      minimal side effects. 

PMID- 24891954
TI  - Melanoma Development and Progression Are Associated with Rad6 Upregulation and
      beta -Catenin Relocation to the Cell Membrane.
AB  - We have previously demonstrated that Rad6 and beta -catenin enhance each other's
      expression through a positive feedback loop to promote breast cancer
      development/progression. While beta -catenin has been implicated in melanoma
      pathogenesis, Rad6 function has not been investigated. Here, we examined the
      relationship between Rad6 and beta -catenin in melanoma development and
      progression. Eighty-eight cutaneous tumors, 30 nevi, 29 primary melanoma, and 29
      metastatic melanomas, were immunostained with anti- beta -catenin and anti-Rad6
      antibodies. Strong expression of Rad6 was observed in only 27% of nevi as
      compared to 100% of primary and 96% of metastatic melanomas. beta -Catenin was
      strongly expressed in 97% of primary and 93% of metastatic melanomas, and unlike
      Rad6, in 93% of nevi. None of the tumors expressed nuclear beta -catenin. beta 
      Catenin was exclusively localized on the cell membrane of 55% of primary, 62% of
      metastatic melanomas, and only 10% of nevi. Cytoplasmic beta -catenin was
      detected in 90% of nevi, 17% of primary, and 8% of metastatic melanoma, whereas
      28% of primary and 30% of metastatic melanomas exhibited beta -catenin at both
      locations. These data suggest that melanoma development and progression are
      associated with Rad6 upregulation and membranous redistribution of beta -catenin
      and that beta -catenin and Rad6 play independent roles in melanoma development. 

PMID- 24891957
TI  - The occurrence of laryngeal penetration and aspiration in patients with glottal
      closure insufficiency.
AB  - Glottal closure during the pharyngeal phase of swallowing is one of the important
      steps in protecting the airway. Generally, it is believed that any deficiency in
      this process can lead to laryngeal penetration and aspiration. This study
      investigated the incidence of laryngeal penetration and aspiration among 44
      patients with glottal closure insufficiencies that were referred for voice and
      swallowing evaluation to our institution. The videostroboscopy and 3 oz water
      swallow test were performed for all of the patients and dysphagic patients were
      screened and referred for videofluoroscopy. Overall, 15.90% of patients
      demonstrated signs of laryngeal penetration (13.63%) and aspiration (2.27%). The
      patients with the pattern of incomplete closure illustrated the highest
      percentage of penetration-aspiration (21.73%, 4.34%) among other GCI patterns.
      Thus, early interventions for these patients' swallowing condition seem
      necessary. 

PMID- 24891958
TI  - Modulation of adult hippocampal neurogenesis by early-life environmental
      challenges triggering immune activation.
AB  - The immune system plays an important role in the communication between the human
      body and the environment, in early development as well as in adulthood. Per se,
      research has shown that factors such as maternal stress and nutrition as well as
      maternal infections can activate the immune system in the infant. A rising number
      of research studies have shown that activation of the immune system in early life
      can augment the risk of some psychiatric disorders in adulthood, such as
      schizophrenia and depression. The mechanisms of such a developmental programming
      effect are unknown; however some preliminary evidence is emerging in the
      literature, which suggests that adult hippocampal neurogenesis may be involved. A
      growing number of studies have shown that pre- and postnatal exposure to an
      inflammatory stimulus can modulate the number of proliferating and
      differentiating neural progenitors in the adult hippocampus, and this can have an
      effect on behaviours of relevance to psychiatric disorders. This review provides
      a summary of these studies and highlights the evidence supporting a neurogenic
      hypothesis of immune developmental programming. 

PMID- 24891960
TI  - Intravascular papillary endothelial hyperplasia: diagnostic sequence and
      literature review of an orofacial lesion.
AB  - Intravascular papillary endothelial hyperplasia or Masson's tumor is a rare
      reactive disease of vascular origin characterized by exuberant proliferation of
      endothelial cells notably occurring within blood vessels of head, neck, and
      extremities. The importance of this entity is its ability to mimic a variety of
      diseases both benign and malignant in the orofacial region. Here, we present a
      case of Masson's tumor within the masseter muscle in a 40-year-old female with
      emphasis on the sequential investigative procedures performed to diagnose this
      entity. 

PMID- 24891961
TI  - Rapid decline of follicular lymphoma-associated chylothorax after low dose
      radiotherapy to retroperitoneal lymphoma localization.
AB  - Chylothorax is caused by disruption or obstruction of the thoracic duct or its
      tributaries that results in the leakage of chyle into the pleural space. A number
      of interventions have been used to treat chylothorax including the treatment of
      the underlying disease. Lymphoma is found in 70% of cases with nontraumatic
      malignant aetiology. Although patients usually have advanced lymphoma,
      supradiaphragmatic disease is not always present. We discuss the case of a 63
      year-old woman presenting with progressive respiratory symptoms due to
      chylothorax. She was diagnosed with a stage IIE retroperitoneal grade 1
      follicular lymphoma extending from the coeliac trunk towards the pelvic inlet.
      Despite thoracocentesis and medium-chain triglycerides (MCT), diet chylothorax
      reoccurred. After low dose radiotherapy (2 * 2 Gy) to the abdominal lymphoma
      there was a marked decrease in lymphadenopathy at the coeliac trunk and a
      complete regression of the pleural fluid. In this case, radiotherapy was shown to
      be an effective nontoxic treatment option for lymphoma-associated chylothorax
      with long-term remission of pleural effusion. 

PMID- 24891962
TI  - Primary gallbladder small lymphocytic lymphoma as a rare postcholecystectomy
      finding.
AB  - Introduction. Primary lymphoma of the gallbladder is an extremely rare entity
      with approximately 50 cases reported so far. In many of these cases the
      presenting symptoms were mimicking symptomatic gallstone disease and the
      diagnosis was made postoperatively, especially when the preoperative imaging
      results were far from suspicious for malignant disease. Patients and Methods. We
      report a case of primary lymphoma of the gallbladder in an 85-year-old man with
      gallstone disease, who was admitted for elective cholecystectomy 2 months after
      an episode of acute cholecystitis and pancreatitis. Histological evaluation of
      the specimen revealed a small lymphocytic lymphoma of the gallbladder. This type
      of primary gallbladder lymphoma has not been previously reported. Discussion. The
      most common primary lymphomas of the gallbladder are MALT lymphomas and diffuse
      large B-cell lymphomas, although a variety of other histological types have been
      reported. The association of these lesions with chronic inflammation is the most
      convincing theory for their pathogenesis. For lesions confined to the
      gallbladder, cholecystectomy is considered to be sufficient, while supplementary
      chemotherapy significantly improves prognosis in more advanced disease. 

PMID- 24891959
TI  - Salicylate-induced auditory perceptual disorders and plastic changes in
      nonclassical auditory centers in rats.
AB  - Previous studies have shown that sodium salicylate (SS) activates not only
      central auditory structures, but also nonauditory regions associated with emotion
      and memory. To identify electrophysiological changes in the nonauditory regions,
      we recorded sound-evoked local field potentials and multiunit discharges from the
      striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS
      treatment produced behavioral evidence of tinnitus and hyperacusis.
      Physiologically, the treatment significantly enhanced sound-evoked neural
      activity in the striatum, amygdala, and hippocampus, but not in the cingulate.
      The enhanced sound evoked response could be linked to the hyperacusis-like
      behavior. Further analysis showed that the enhancement of sound-evoked activity
      occurred predominantly at the midfrequencies, likely reflecting shifts of neurons
      towards the midfrequency range after SS-treatment as observed in our previous
      studies in the auditory cortex and amygdala. The increased number of midfrequency
      neurons would lead to a relative higher number of total spontaneous discharges in
      the midfrequency region, even though the mean discharge rate of each neuron may
      not increase. The tonotopical overactivity in the midfrequency region in quiet
      may potentially lead to tonal sensation of midfrequency (the tinnitus). The
      neural changes in the amygdala and hippocampus may also contribute to the
      negative effect that patients associate with their tinnitus. 

PMID- 24891964
TI  - Mucinous cystadenoma arising in a mature cystic teratoma in a 25-year-old
      patient.
AB  - Coexistence of a mucinous cystadenoma arising in a mature cystic teratoma is
      infrequently reported. Herein a case of a 25-year-old woman diagnosed with a
      right ovarian mucinous cystadenoma arising in a mature cystic teratoma is
      reported. She presented with lower right abdominal discomfort. Ultrasound showed
      a 14.8 * 7.9 * 12.5 cm structure on the right adnexa. She underwent a diagnostic
      laparoscopy, which was converted to exploratory laparotomy, during which a right
      salpingo-oophorectomy was performed. 

PMID- 24891963
TI  - Intrapartum diagnosis and treatment of longitudinal vaginal septum.
AB  - Longitudinal vaginal septum is a rare Mullerian malformation that may be
      associated with dyspareunia, dysmenorrhea, primary amenorrhea, and infertility.
      In this report, the authors present a case of longitudinal vaginal septum in a 15
      year-old patient with a full-term pregnancy whose diagnosis was only made during
      labor following bidigital vaginal and speculum examination. Septoplasty was
      performed during the second stage of labor. Both mother and child progressed
      satisfactorily and were discharged from hospital in good health. Six months
      later, ultrasonography, hysterosalpingography, and hysteroscopy were carried out
      and no other associated abnormality was found. 

PMID- 24891965
TI  - The development of dorsal nasal cyst formation after rhinoplasty and its
      reconstruction with conchal cartilage.
AB  - The dorsal nasal cyst formation is a rare and late complication of rhinoplasty.
      It has been rarely reported in the literature and it is usually mucous cysts.
      Migration and planting to the subcutaneous space during the surgical procedure
      has been recognized as the formation mechanism. This case report has presented 42
      year-old male patient with a destructing dorsal nasal mucous cyst that developed
      10 years after the rhinoplasty operation. There was no complication in the
      primary rhinoplasty and the patient was satisfied with his appearance. There was
      a swelling of the nasal dorsum over the past year and surgical excision of the
      cyst was performed. During the surgery, the defect was reconstructed with conchal
      cartilage. There was no recurrence during follow-up. 

PMID- 24891967
TI  - Oral floor and gingival metastasis of cholangiocarcinoma: a case report and
      review of the literature.
AB  - The oral cavity is very unusual site of metastases even though wide spread
      metastatic disease may be present. The most common primary sites that metastasize
      to the oral cavity are lung, kidney, breast, and hepatocellular carcinoma. We
      present a rare case of a 77-year-old Caucasian female with metastasis from a
      cholangiocarcinoma to the oral floor contiguous with lingual gingival mucosa. The
      patient presented with left sided rib pain. A CT scan of the chest, abdomen, and
      pelvis showed multiple pulmonary nodules and a single dominant mass in the right
      lobe of the liver. This tumor was 6.5 cm with multiple satellite lesions
      surrounding it. The liver biopsy was diagnostic of a moderately to poorly
      differentiated adenocarcinoma, consistent with a primary cholangiocarcinoma.
      After undergoing one cycle of gemcitabine chemotherapy, the patient noticed an
      extremely rapidly growing mass involving her right lower gingiva and the entire
      right floor of her mouth. The biopsy of that mass also showed a moderately to
      poorly differentiated adenocarcinoma. The gingival tumor had a similar
      cytomorphology and immunophenotype as her cholangiocarcinoma. Therefore, an
      unusual site for metastatic cholangiocarcinoma was confirmed. 

PMID- 24891966
TI  - Clinical history and colliquative myocytolysis are keys to the diagnosis of
      shoshin beriberi.
AB  - Cardiovascular beriberi presents as either the fulminant (Shoshin beriberi) or
      chronic form. Shoshin beriberi is a rare disease that may lead to a fatal outcome
      if the patient does not receive appropriate treatment. In the present report, we
      describe the case of a 66-year-old man presenting with leg edema and dyspnea at
      rest. Clinical presentations were nonalcoholic Shoshin beriberi and lactate
      accumulation; however, clinical improvement was observed after the administration
      of thiamine. His pretherapy thiamine level (2.1  MU g/dL) was consistent with a
      diagnosis of beriberi. Based on the findings of the present case, we believe that
      a diagnosis can be made in patients with a clinical history that is consistent
      with that of Shoshin beriberi, combined with low thiamine levels, lactate
      accumulation, and colliquative myocytolysis. Learning Objective. Shoshin beriberi
      is often misdiagnosed because of its rarity; a detailed clinical history and
      characteristic myocardial histopathology changes may be useful for making a
      definite diagnosis. 

PMID- 24891968
TI  - Clostridium sordellii as a Cause of Fatal Septic Shock in a Child with Hemolytic
      Uremic Syndrome.
AB  - Clostridium sordellii is a toxin producing ubiquitous gram-positive anaerobe,
      mainly associated with trauma, soft tissue skin infections, and gynecologic
      infection. We report a unique case of a new strain of Clostridium sordellii (not
      present in the Center for Disease Control (CDC) database) infection induced toxic
      shock syndrome in a previously healthy two-year-old male with colitis-related
      hemolytic uremic syndrome (HUS). The patient presented with dehydration,
      vomiting, and bloody diarrhea. He was transferred to the pediatric critical care
      unit (PICU) for initiation of peritoneal dialysis (PD). Due to increased edema
      and intolerance of PD, he was transitioned to hemodialysis through a femoral
      vascular catheter. He subsequently developed severe septic shock with persistent
      leukocytosis and hypotension, resulting in subsequent death. Stool culture
      confirmed Shiga toxin producing Escherichia coli 0157:H7. A blood culture was
      positively identified for Clostridium sordellii. Clostridium sordelli is rarely
      reported in children; to our knowledge this is the first case described in a
      pediatric patient with HUS. 

PMID- 24891969
TI  - Abiraterone acetate and castration resistant ductal adenocarcinoma of the
      prostate.
AB  - Ductal adenocarcinoma of the prostate is a rare histological variant that only
      represents <1% of prostate tumors. This histological variant has several
      important clinical implications with respect to their evolution, clinical
      prognosis, and treatment. We report the case of a 64-year-old patient with ductal
      adenocarcinoma of the prostate, which progresses to castration-resistant prostate
      cancer, that was treated with abiraterone acetate with good clinical response, to
      our knowledge, the first case of ductal adenocarcinoma of the prostate in
      treatment with abiraterone acetate. 

PMID- 24891970
TI  - Prevention of post-ERCP pancreatitis.
AB  - Post-procedure pancreatitis is the most common complication of endoscopic
      retrograde cholangio pancreatography (ERCP) and carries a high morbidity and
      mortality occurring in at least 3%-5% of all procedures. We reviewed the
      available literature searching for "ERCP" and "pancreatitis" and "post-ERCP
      pancreatitis". in PubMed and Medline. This review looks at the diagnosis, risk
      factors, causes and methods of preventing post-procedure pancreatitis. These
      include the evidence for patient selection, endoscopic techniques and
      pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right
      patient for the procedure by a risk benefits assessment is the best way of
      avoiding unnecessary ERCPs. Risk is particularly high in young women with
      sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few
      numbers of subjects and hence difficult to appraise. Meta-analyses have helped
      screen for promising modalities of prophylaxis. At present, evidence is emerging
      that pancreatic stenting of patients with SOD and rectally administered
      nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk
      of post-procedure pancreatitis. A recent meta-analysis have demonstrated that
      rectally administered indomethecin, just before or after ERCP is associated with
      significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34
      0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these
      prophylactic measures will begin to be increasingly practised in high risk
      groups. 

PMID- 24891971
TI  - Pathophysiology of autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a recently discovered form of pancreatitis and
      represents one of the diseases of the pancreas which can be cured and healed
      medically. International consensus diagnostic criteria have been developed, and
      the clinical phenotypes associated with the histopathologic patterns of
      lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric
      pancreatitis should be referred to as type 1 and type 2 AIP, respectively. Most
      importantly, in type 1 AIP, the pancreatic manifestations are associated with
      other extrapancreatic disorders, resembling an immunoglobulin G4 (IgG4)-related
      disease. In addition, the pancreas of a patient with AIP is often infiltrated by
      various types of immune cells; the cluster of differentiation (CD) 4 or CD8 T
      lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic
      parenchyma and other involved organs in AIP and factors regulating T-cell
      function may influence the development of AIP. From a genetic point of view, it
      has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly
      more frequent in patients with AIP when compared to those with chronic calcifying
      pancreatitis, and that only DQB1*0302 had a significant association with the
      relapse of AIP. Finally, it has been found that the polymorphic genes encoding
      cytotoxic T lymphocyte-associated antigen 4, a key negative regulator of the T
      cell immune response, are associated with AIP in a Chinese population. Even if
      these data are not concordant, it is possible that physiological IgG4 responses
      are induced by prolonged antigen exposure and controlled by type 2 helper T
      cells. We reviewed the current concepts regarding the pathophysiology of this
      intriguing disease, focusing on the importance of the humoral and cellular immune
      responses. 

PMID- 24891973
TI  - Electrophysiology as a tool to unravel the origin of pancreatic pain.
AB  - Intense abdominal pain is the most common symptom in chronic pancreatitis, but
      the underlying mechanisms are not completely understood and pain management
      remains a significant clinical challenge. The focus of pain origin in chronic
      pancreatitis traditionally has been on the pancreatic gland, assuming pain to
      originate in the pancreas or its surrounding organs. However, research in the
      last decade points to abnormal central nervous system pain processing. For this
      reason, electroencephalography has been receiving increasing attention. In
      contrast to imaging methods such as functional magnetic resonance imaging and
      positron emission tomography, electroencephalogram has excellent temporal
      resolution making it possible to investigate central processing of pain on a
      millisecond time scale. Moreover, continuously advancing methodology made it
      possible to explore brain sources responsible for generation of evoked potentials
      and hence to study brain reorganization due to pain in chronic pancreatitis. The
      aim of this review is to give an overview of the current methods and findings in
      electroencephalography as a tool to unravel the origin of pancreatic pain. 

PMID- 24891974
TI  - Quality of healing of gastric ulcers: Natural products beyond acid suppression.
AB  - Gastric ulcer is a chronic disease featured with unexpected complications,
      including bleeding, stenosis and perforation, as well as a high incidence of
      recurrence. Clinical treatments for gastric ulcer have allowed the rapid
      development of potent anti-ulcer drugs during the last several decades. Gastric
      ulcer healing is successful with conventional treatments including H2-receptor
      antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer
      healing and prevention of complications. Additionally, Helicobacter pylori
      eradication therapy is effective in reducing ulcer recurrence and leads to
      physiological changes in the gastric mucosa which affect the ulcer healing
      process. However, in spite of these advancements, some patients have suffered
      from recurrence or intractability in spite of continuous anti-ulcer therapy. A
      new concept of the quality of ulcer healing (QOUH) was initiated that considers
      the reconstruction of the mucosal structure and its function for preventing ulcer
      recurrence. Although several gastroprotection provided these achievements of the
      QOUH, which PPI or other acid suppressants did not accomplish, we found that
      gastroprotection that originated from natural products, such as a newer
      formulation from either Artemisia or S-allyl cysteine from garlic, were very
      effective in the QOUH, as well as improving clinical symptoms with fewer side
      effects. In this review, we will introduce the importance of the QOUH in ulcer
      healing and the achievements from natural products. 

PMID- 24891972
TI  - Intestinal barrier: A gentlemen's agreement between microbiota and immunity.
AB  - Our body is colonized by more than a hundred trillion commensals, represented by
      viruses, bacteria and fungi. This complex interaction has shown that the
      microbiome system contributes to the host's adaptation to its environment,
      providing genes and functionality that give flexibility of diet and modulate the
      immune system in order not to reject these symbionts. In the intestine,
      specifically, the microbiota helps developing organ structures, participates of
      the metabolism of nutrients and induces immunity. Certain components of the
      microbiota have been shown to trigger inflammatory responses, whereas others,
      anti-inflammatory responses. The diversity and the composition of the microbiota,
      thus, play a key role in the maintenance of intestinal homeostasis and explain
      partially the link between intestinal microbiota changes and gut-related
      disorders in humans. Tight junction proteins are key molecules for determination
      of the paracellular permeability. In the context of intestinal inflammatory
      diseases, the intestinal barrier is compromised, and decreased expression and
      differential distribution of tight junction proteins is observed. It is still
      unclear what is the nature of the luminal or mucosal factors that affect the
      tight junction proteins function, but the modulation of the immune cells found in
      the intestinal lamina propria is hypothesized as having a role in this
      modulation. In this review, we provide an overview of the current understanding
      of the interaction of the gut microbiota with the immune system in the
      development and maintenance of the intestinal barrier. 

PMID- 24891975
TI  - Microscopic colitis: Common cause of unexplained nonbloody diarrhea.
AB  - Microscopic colitis (MC) is characterized by chronic, watery, secretory diarrhea,
      with a normal or near normal gross appearance of the colonic mucosa. Biopsy is
      diagnostic and usually reveals either lymphocytic colitis or collagenous colitis.
      The symptoms of collagenous colitis appear most commonly in the sixth decade.
      Patients report watery, nonbloody diarrhea of a chronic, intermittent or chronic
      recurrent course. With collagenous colitis, the major microscopic characteristic
      is a thickened collagen layer beneath the colonic mucosa, and with lymphocytic
      colitis, an increased number of intraepithelial lymphocytes. Histological workup
      can confirm a diagnosis of MC and distinguish the two distinct histological
      forms, namely, collagenous and lymphocytic colitis. Presently, both forms are
      diagnosed and treated in the same way; thus, the description of the two forms is
      not of clinical value although this may change in the future. Since microscopic
      colitis was first described in 1976 and only recently recognized as a common
      cause of diarrhea, many practicing physicians may not be aware of this entity. In
      this review, we outline the epidemiology, risk factors associated with MC, its
      etiopathogenesis, the approach to diagnosis and the management of these
      individuals. 

PMID- 24891976
TI  - "Mucosal healing" in ulcerative colitis: Between clinical evidence and market
      suggestion.
AB  - In recent decades, the prominent role of endoscopy in the management of
      ulcerative colitis (UC) has been translated into the concept of mucosal healing
      (MH) as a fundamental therapeutic end-point. This is partially the consequence of
      growing evidence of a positive prognostic role of MH on the disease course and
      partially due to market cues indicating a higher rate of MH in patients treated
      by novel potent biologic agents. The aim of the present review is to clarify the
      current knowledge of MH in UC, analyzing the definition, the putative prognostic
      role and the association of MH with the current drugs used to treat UC patients.
      Because solid data about the management of UC patients based solely on the
      healing of the mucosa are not yet available, a tailored approach for individual
      patients thatconsiders the natural history of UC and the presence of prognostic
      indicators of aggressive disease is desirable. Consequently, unnecessary
      examinations and treatment would be avoided and restricted to UC patients who
      require the maximum amount of effort to affect the disease course in the short
      and long term. 

PMID- 24891977
TI  - Implication of miRNAs for inflammatory bowel disease treatment: Systematic
      review.
AB  - Inflammatory bowel disease (IBD) is believed to develop via a complex interaction
      between genetic, environmental factors and the mucosal immune system. Crohn's
      disease and ulcerative colitis are two major clinical forms of IBD. MicroRNAs
      (miRNAs) are a class of small, endogenous, noncoding RNA molecules, and
      evolutionary conserved in animals and plants. It controls protein production at
      the post-transcriptional level by targeting mRNAs for translational repression or
      degradation. MiRNAs are important in many biological processes, such as signal
      transduction, cellular proliferation, differentiation and apoptosis. Considerable
      attention has been paid on the key role of miRNAs in autoimmune and inflammatory
      disease, especially IBD. Recent studies have identified altered miRNA profiles in
      ulcerative colitis, Crohn's disease and inflammatory bowel disease-associated
      colorectal cancer. In addition, emerging data have implicated that special miRNAs
      which suppress functional targets play a critical role in regulating key
      pathogenic mechanism in IBD. MiRNAs were found involving in regulation of nuclear
      transcription factor kappa B pathway (e.g., miR-146a, miR-146b, miR-122, miR-132,
      miR-126), intestinal epithelial barrier function (e.g., miR-21, miR-150, miR
      200b) and the autophagic activity (e.g., miR-30c, miR-130a, miR-106b, miR-93, miR
      196). This review aims at discussing recent advances in our understanding of
      miRNAs in IBD pathogenesis, their role as disease biomarkers, and perspective for
      future investigation and clinical application. 

PMID- 24891978
TI  - Review of the diagnosis, classification and management of autoimmune
      pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, with as yet
      undetermined incidence and prevalence in the general population. Our
      understanding of it continues to evolve. In the last few years, 2 separate
      subtypes have been identified: type 1 AIP has been recognised as the pancreatic
      manifestation of a multiorgan disease, named immunoglobulin G4 (IgG4)-related
      disease while type 2 AIP is a pancreas specific disorder not associated with
      IgG4. International criteria for the diagnosis of AIP have been defined: the
      HISORt criteria from the Mayo clinic, the Japan consensus criteria and, most
      recently, the international association of pancreatology "International Consensus
      Diagnostic Criteria". Despite this, in clinical practice it can still be very
      difficult to confirm the diagnosis and differentiate AIP from a pancreatic
      cancer. There are no large studies into the long-term prognosis and management of
      relapses of AIP, and there is even less information at present regarding the Type
      2 AIP subtype. Further studies are necessary to clarify the pathogenesis,
      treatment and long-term outcomes of this disease. Critically for clinicians,
      making the correct diagnosis and differentiating the disease from pancreatic
      cancer is of the utmost importance and the greatest challenge. 

PMID- 24891979
TI  - Alcoholic pancreatitis: A tale of spirits and bacteria.
AB  - Alcohol is a major cause of chronic pancreatitis. About 5% of alcoholics will
      ever suffer from pancreatitis, suggesting that additional co-factors are required
      to trigger an overt disease. Experimental work has implicated lipopolysaccharide,
      from gut-derived bacteria, as a potential co-factor of alcoholic pancreatitis.
      This review discusses the effects of alcohol on the gut flora, the gut barrier,
      the liver-and the pancreas and proposes potential interventional strategies. A
      better understanding of the interaction between the gut, the liver and the
      pancreas may provide valuable insight into the pathophysiology of alcoholic
      pancreatitis. 

PMID- 24891980
TI  - Low grade dysplasia in Barrett's esophagus: Should we worry?
AB  - The optimal management for low-grade dysplasia (LGD) in Barrett's esophagus is
      unclear. In this article the importance of LGD is discussed, including the
      significant risk of progression to esophageal adenocarcinoma. Endoscopic
      surveillance is a management option but is plagued by sampling error and issues
      of suboptimal endoscopy. Furthermore endoscopic surveillance has not been
      demonstrated to be cost-effective or to reduce cancer mortality. The emergence of
      endoluminal therapy over the past decade has resulted in a paradigm shift in the
      management of LGD. Ablative therapy, including radiofrequency ablation, has
      demonstrated promising results in the management of LGD with regards to safety,
      cost-effectiveness, durability and reduction in cancer risk. It is, however,
      vital that a shared-decision making process occurs between the physician and the
      patient as to the preferred management of LGD. As such the management of LGD
      should be "individualised." 

PMID- 24891981
TI  - Endoscopic surveillance strategy after endoscopic resection for early gastric
      cancer.
AB  - Early detection of early gastric cancer (EGC) is important to improve the
      prognosis of patients with gastric cancer. Recent advances in endoscopic
      modalities and treatment devices, such as image-enhanced endoscopy and high
      frequency generators, may make endoscopic treatment, such as endoscopic
      submucosal dissection, a therapeutic option for gastric intraepithelial
      neoplasia. Consequently, short-term outcomes of endoscopic resection (ER) for EGC
      have improved. Therefore, surveillance with endoscopy after ER for EGC is
      becoming more important, but how to perform endoscopic surveillance after ER has
      not been established, even though the follow-up strategy for more advanced
      gastric cancer has been outlined. Therefore, a surveillance strategy for patients
      with EGC after ER is needed. 

PMID- 24891982
TI  - Role of gamma-delta T cells in liver inflammation and fibrosis.
AB  - Conventional adaptive T cell responses contribute to liver inflammation and
      fibrogenesis, especially in chronic viral infections and autoimmune hepatitis.
      However, the role of unconventional gamma-delta (gammadelta) T cells in liver
      diseases is less clear. In the past two decades, accumulating evidence revealed
      that gammadelta T cell numbers remarkably increase in the liver upon various
      inflammatory conditions in mice and humans. More recent studies demonstrated that
      the functional effect of gammadelta T cells on liver disease progression depends
      on the subsets involved, which can be identified by the expression of distinct T
      cell receptor chains and of specific cytokines. Fascinatingly, gammadelta T cells
      may have protective as well as pathogenic functions in liver diseases. Interferon
      gamma-producing gammadelta T cells, for example, induce apoptosis in hepatocytes
      but also in hepatic tumor cells; while interleukin-17-expressing gammadelta T
      cells can downregulate pathogenic effector functions of other immune cells and
      can promote apoptosis of fibrogenic stellate cells. However, the results obtained
      in human liver disease as well as murine models are not fully conclusive at
      present, and the effects of gammadelta T cells on the outcome of liver disease
      might vary dependent on etiology and stage of disease. Further definitions of the
      gammadelta T cell subsets involved in acute and chronic liver inflammation, as
      well as their effector cytokines might uncover whether interference with
      gammadelta T cells could be a useful target for the treatment of liver disease. 

PMID- 24891983
TI  - Liver biopsy: Analysis of results of two specialist teams.
AB  - AIM: To analyze the safety and the adequacy of a sample of liver biopsies (LB)
      obtained by gastroenterologist (G) and interventional radiologist (IR) teams.
      METHODS: Medical records of consecutive patients evaluated at our GI unit from
      01/01/2004 to 31/12/2010 for whom LB was considered necessary to diagnose and/or
      stage liver disease, both in the setting of day hospital and regular admission
      (RA) care, were retrieved and the data entered in a database. Patients were
      divided into two groups: one undergoing an ultrasonography (US)-assisted
      procedure by the G team and one undergoing US-guided biopsy by the IR team. For
      the first group, an intercostal approach (US-assisted) and a Menghini modified
      type needle 16 G (length 90 mm) were used. The IR team used a subcostal approach
      (US-guided) and a semiautomatic modified Menghini type needle 18 G (length 150
      mm). All the biopsies were evaluated for appropriateness according to the current
      guidelines. The number of portal tracts present in each biopsy was assessed by a
      revision performed by a single pathologist unaware of the previous pathology
      report. Clinical, laboratory and demographic patient characteristics, the adverse
      events rate and the diagnostic adequacy of LB were analyzed. RESULTS: During the
      study period, 226 patients, 126 males (56%) and 100 females (44%), underwent LB:
      167 (74%) were carried out by the G team, whereas 59 (26%) by the IR team. LB was
      mostly performed in a day hospital setting by the G team, while IR completed more
      procedures on inpatients (P < 0.0001). The groups did not differ in median age,
      body mass index (BMI), presence of comorbidities and coagulation parameters.
      Complications occurred in 26 patients (16 G team vs 10 IR team, P = 0.15). Most
      gross samples obtained were considered suitable for basal histological
      evaluation, with no difference among the two teams (96.4% G team vs 91.5% IR, P =
      0.16). However, the samples obtained by the G team had a higher mean number of
      portal tracts (G team 9.5 +/- 4.8; range 1-29 vs IR team 7.8 +/- 4.1; range 1-20)
      (P = 0.0192) and a longer mean length (G team 22 mm +/- 8.8 vs IR team 15 +/- 6.5
      mm) (P = 0.0001). CONCLUSION: LB can be performed with similar outcomes both by G
      and IR. Use of larger dimension needles allows obtaining better samples, with a
      similar rate of adverse events.

PMID- 24891984
TI  - Controversial issues regarding the roles of IL-10 and IFN-gamma in
      active/inactive chronic hepatitis B.
AB  - According to the important roles played by cytokines in induction of appropriate
      immune responses against hepatitis B virus (HBV), Dimitropoulou et al have
      examined the important cytokines in their patients. They showed that the serum
      levels of interleukin 10 (IL-10) and interferon-gamma (IFN-gamma) were decreased
      in patients with HBeAg-negative chronic active hepatitis B compared with the
      inactive hepatitis B virus carriers (Dimitropoulou et al 2013). The controversy
      can be considered regarding the decreased serum levels of IFN-gamma in the HBeAg
      negative chronic active hepatitis B patients. They concluded that subsequent to
      decreased expression of IFN-gamma, the process of HBV proliferation led to liver
      diseases. Previous studies stated that HBV is not directly cytopathic for the
      infected hepatocytes and immune responses are the main reason for destruction of
      hepatocytes (Chisari et al, 2010). Scientists believe that immune responses
      against HBV are stronger in active forms of chronic HBV infected patients than
      inactive forms (Zhang et al, 2012). Therefore, the findings from Dimitropoulou et
      al may deserve further attention and discussion. Additionally, downregulation of
      IL-10 in chronically active hepatitis B infected patients has also confirmed our
      claim. IL-10 is an anti-inflammatory cytokine and its expression is increased in
      inactive forms in order to downregulate immune responses (Arababadi et al, 2012).
      Thus, based on the results from Dimitropoulou et al, it can be concluded that
      increased immune responses in chronically active hepatitis B infected patients
      are related to declined expression of IL-10 and interestingly IFN-gamma is not
      involved in induction of immune responses in these patients. 

PMID- 24891986
TI  - Supporting a healthy microbiome and patient outcomes with probiotics.

PMID- 24891987
TI  - The human microbiome.

PMID- 24891988
TI  - Diversity: from diet to flora to life.

PMID- 24891985
TI  - AMP-activated Protein Kinase (AMPK): Does This Master Regulator of Cellular
      Energy State Distinguish Insulin Sensitive from Insulin Resistant Obesity?
AB  - Although a correlation exists between obesity and insulin resistance, roughly 25
      % of obese individuals are insulin sensitive. AMP-activated protein kinase (AMPK)
      is a cellular energy sensor that among its many actions, integrates diverse
      physiological signals to restore energy balance. In addition, in many situations
      it also increases insulin sensitivity. In this context, AMPK activity is
      decreased in very obese individuals undergoing bariatric surgery who are insulin
      resistant compared to equally obese patients who are insulin sensitive. In this
      review, we will both explore what distinguishes these individuals, and evaluate
      the evidence that diminished AMPK is associated with insulin resistance and
      metabolic syndrome-associated disorders in other circumstances. 

PMID- 24891989
TI  - Frequency of abnormal fecal biomarkers in irritable bowel syndrome.
AB  - PRIMARY STUDY OBJECTIVE: Determine the frequency of abnormal fecal biomarker test
      results in patients with 13 irritable bowel syndrome (IBS)-related ICD-9
      (International Statistical Classification of Diseases and Related Health
      Problems) codes. STUDY DESIGN: Quantitative review of de-identified records from
      patients in whom IBS was a possible diagnosis. METHODS: Records were selected for
      analysis if they included any of 13 IBS-related diagnostic codes and laboratory
      test results of fecal testing for all biomarkers of interest. Data collection was
      restricted to one 12-month period. Frequency distributions were calculated to
      identify rates of abnormal results for each biomarker within the total number of
      tests conducted in the eligible population. RESULTS: Two thousand, two hundred
      fifty-six records were included in the study, of which 1867 (82.8%) included at
      least one abnormal value. Quantitative stool culture for beneficial bacteria
      (Lactobacillus and Bifidobacterium) indicated low growth suggestive of intestinal
      dysbiosis in 73.1% of records, followed by abnormally elevated eosinophil protein
      X (suggestive of food allergy) in 14.3%, elevated calprotectin (suggestive of
      inflammation) in 12.1%, detection of parasites in 7.5%, and low pancreatic
      elastase (suggestive of exocrine pancreatic insufficiency) in 7.1%. CONCLUSIONS:
      Abnormal fecal biomarkers are prevalent in patients with diagnoses suggestive of
      IBS. Abnormal fecal biomarker testing, if confirmed in additional independent
      clinical trials, could substantially reduce the economic costs associated with
      diagnosis and management of IBS.

PMID- 24891991
TI  - Novel Testing Enhances Irritable Bowel Syndrome Medical Management: The IMMINENT
      Study.
AB  - PRIMARY STUDY OBJECTIVE: To evaluate the economic utility of a fecal biomarker
      panel structured to suggest alternative, treatable diagnoses in patients with
      symptoms of irritable bowel syndrome (IBS) by quantifying, comparing, and
      contrasting health service costs between tested and non-tested patients. STUDY
      DESIGN: Retrospective, matched cohort study comparing direct medical costs for
      IBS patients undergoing fecal biomarker testing with those of matched control
      subjects. METHODS: We examined de-identified medical and pharmacy claims of a
      large American pharmacy benefit manager to identify plan members who underwent
      panel testing, were eligible for covered benefits for at least 180 days prior to
      the test date, and had data available for 30, 90, and 365 days after that date.
      We used propensity score matching to develop population-based control cohorts for
      each tested cohort, comprised of records with IBS-related diagnoses but for which
      panel testing was not performed. Primary outcome measures were diagnostic and
      medical services costs as determined from claims data. RESULTS: Two hundred nine
      records from tested subjects met inclusion criteria. The only significant
      baseline differences between groups were laboratory costs, which were
      significantly higher in each tested cohort. At each follow-up time point, total
      medical and gastrointestinal procedural costs were significantly higher in non
      tested cohorts. Within tested cohorts, costs declined significantly from
      baseline, while costs rose significantly in non-tested control cohorts; these
      differences were also significant between groups at each time point. CONCLUSIONS:
      Structured fecal biomarker panel testing was associated with significantly lower
      medical and gastrointestinal procedural costs in this study of patients with IBS
      symptoms.

PMID- 24891990
TI  - Herbal therapy is equivalent to rifaximin for the treatment of small intestinal
      bacterial overgrowth.
AB  - OBJECTIVE: Patients with small intestine bacterial overgrowth (SIBO) have chronic
      intestinal and extraintestinal symptomatology which adversely affects their
      quality of life. Present treatment of SIBO is limited to oral antibiotics with
      variable success. A growing number of patients are interested in using
      complementary and alternative therapies for their gastrointestinal health. The
      objective was to determine the remission rate of SIBO using either the antibiotic
      rifaximin or herbals in a tertiary care referral gastroenterology practice.
      DESIGN: One hundred and four patients who tested positive for newly diagnosed
      SIBO by lactulose breath testing (LBT) were offered either rifaximin 1200 mg
      daily vs herbal therapy for 4 weeks with repeat LBT post-treatment. RESULTS:
      Three hundred ninety-six patients underwent LBT for suspected SIBO, of which 251
      (63.4%) were positive 165 underwent treatment and 104 had a follow-up LBT. Of the
      37 patients who received herbal therapy, 17 (46%) had a negative follow-up LBT
      compared to 23/67 (34%) of rifaximin users (P=.24). The odds ratio of having a
      negative LBT after taking herbal therapy as compared to rifaximin was 1.85
      (CI=0.77-4.41, P=.17) once adjusted for age, gender, SIBO risk factors and IBS
      status. Fourteen of the 44 (31.8%) rifaximin non-responders were offered herbal
      rescue therapy, with 8 of the 14 (57.1%) having a negative LBT after completing
      the rescue herbal therapy, while 10 non-responders were offered triple
      antibiotics with 6 responding (60%, P=.89). Adverse effects were reported among
      the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2
      cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea
      was reported in the herbal therapy arm, which did not reach statistical
      significance (P=.22). CONCLUSION: SIBO is widely prevalent in a tertiary referral
      gastroenterology practice. Herbal therapies are at least as effective as
      rifaximin for resolution of SIBO by LBT. Herbals also appear to be as effective
      as triple antibiotic therapy for SIBO rescue therapy for rifaximin non
      responders. Further, prospective studies are needed to validate these findings
      and explore additional alternative therapies in patients with refractory SIBO.

PMID- 24891995
TI  - Elevated Deoxycholic Acid and Idiopathic Recurrent Acute Pancreatitis: A Case
      Report With 48 Months of Follow-up.
AB  - Recurrent pancreatitis is a potentially life-threatening condition with a well
      established differential diagnosis. In a significant number of cases, no
      explanation exists. This case report documents one patient with a clear pattern
      of recurrent acute pancreatitis and no identifiable cause despite great effort.
      After 7 years of recurrent symptoms, she was found to have marked elevation of
      fecal deoxycholic acid (DCA), a secondary bile acid used to precipitate
      pancreatitis in animal models. This report documents cessation of
      symptoms/hospitalizations with normalization of her fecal DCA levels. This
      secondary bile acid is easily measured in stool. Needed now is an observational
      study of fecal DCA levels in patients with recurrent acute pancreatitis. 

PMID- 24891992
TI  - Three measurable and modifiable enteric microbial biotransformations relevant to
      cancer prevention and treatment.
AB  - Interdisciplinary scientific evaluation of the human microbiota has identified
      three enteric microbial biotransformations of particular relevance for human
      health and well-being, especially cancer. Two biotransformations are
      counterproductive; one is productive. First, selective bacteria can reverse
      beneficial hepatic hydroxylation to produce toxic secondary bile acids,
      especially deoxycholic acid. Second, numerous bacterial species can reverse
      hepatic detoxification-in a sense, retoxify hormones and xeonobiotics-by
      deglucuronidation. Third, numerous enteric bacteria can effect a very positive
      biotransformation through the production of butyrate, a small chain fatty acid
      with anti-cancer activity. Each biotransformation is addressed in sequence for
      its relevance in representative gastrointestinal and extra-intestinal cancers.
      This is not a complete review of their connection with every type of cancer. The
      intent is to introduce the reader to clinically relevant microbial biochemistry
      plus the emerging evidence that links these to both carcinogenesis and treatment.
      Included is the evidence base to guide counseling for potentially helpful dietary
      adjustments. 

PMID- 24891996
TI  - Fecal microbiota transplantation: an interview with alexander khoruts.

PMID- 24891993
TI  - The role of the gut microbiome in the pathogenesis and treatment of obesity.

PMID- 24891994
TI  - The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of
      Non-liver Diseases.
AB  - Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic
      acid (UDCA), a US Food and Drug Administration-approved hydrophilic bile acid for
      the treatment of certain cholestatic liver diseases. There is a growing body of
      research on the mechanism(s) of TUDCA and its potential therapeutic effect on a
      wide variety of non-liver diseases. Both UDCA and TUDCA are potent inhibitors of
      apoptosis, in part by interfering with the upstream mitochondrial pathway of cell
      death, inhibiting oxygen-radical production, reducing endoplasmic reticulum (ER)
      stress, and stabilizing the unfolded protein response (UPR). Several studies have
      demonstrated that TUDCA serves as an anti-apoptotic agent for a number of
      neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's
      disease, Parkinson's disease, and Huntington's disease. In addition, TUDCA plays
      an important role in protecting against cell death in certain retinal disorders,
      such as retinitis pigmentosa. It has been shown to reduce ER stress associated
      with elevated glucose levels in diabetes by inhibiting caspase activation, up
      regulating the UPR, and inhibiting reactive oxygen species. Obesity, stroke,
      acute myocardial infarction, spinal cord injury, and a long list of acute and
      chronic non-liver diseases associated with apoptosis are all potential
      therapeutic targets for T/UDCA. A growing number of pre-clinical and clinical
      studies underscore the potential benefit of this simple, naturally occurring bile
      acid, which has been used in Chinese medicine for more than 3000 years. 

PMID- 24891997
TI  - Sparse tensor phase space Galerkin approximation for radiative transport.
AB  - ABSTRACT: We develop, analyze, and test a sparse tensor product phase space
      Galerkin discretization framework for the stationary monochromatic radiative
      transfer problem with scattering. The mathematical model describes the transport
      of radiation on a phase space of the Cartesian product of a typically three
      dimensional physical domain and two-dimensional angular domain. Known solution
      methods such as the discrete ordinates method and a spherical harmonics method
      are derived from the presented Galerkin framework. We construct sparse versions
      of these well-established methods from the framework and prove that these sparse
      tensor discretizations break the "curse of dimensionality": essentially (up to
      logarithmic factors in the total number of degrees of freedom) the solution
      complexity increases only as in a problem posed in the physical domain alone,
      while asymptotic convergence orders in terms of the discretization parameters
      remain essentially equal to those of a full tensor phase space Galerkin
      discretization. Algorithmically we compute the sparse tensor approximations by
      the combination technique. In numerical experiments on 2+1 and 3+2 dimensional
      phase spaces we demonstrate that the advantages of sparse tensorization can be
      leveraged in applications. 2010 MATHEMATICS SUBJECT CLASSIFICATION: 35Q79; 65N12;
      65N30; 65N35.

PMID- 24891998
TI  - Effects of High-concentration contrast material and low-voltage CT on contrast
      for multiphasic CT of the upper abdomen: comparison using the simulation with
      virtual monochromatic imaging obtained by fast-switch kVp dual-energy CT.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of high
      concentration contrast material and low-voltage CT simulated by virtual
      monochromatic (VM) imaging on contrast enhancement at multiphasic CT of the upper
      abdomen. METHODS: This study included 72 patients who underwent CT during early
      arterial (EAP), late arterial and portal venous phases after 300-mgI/ml (Group A;
      34 patients) or 350-mg/ml (Group B; 38 patients) contrast-material injection at
      the same volumetric rate (0.067 mL/sec/kg). VM images were generated at 50 and 65
      keV. Contrast-to-noise ratios (CNRs) of aorta, portal vein, and liver parenchyma
      were calculated and statistically compared. RESULTS: Mean CNRs for 50-keV VM
      images were significantly higher than 65-keV VM images of each organ at any
      phases (p < 0.05), except for hepatic parenchyma in EAP. Aortic CNRs in EAP on 65
      and 50-keV images of Group B were significantly higher than Group A (p <0.05,
      respectively). Aortic CNR on 50-keV images of Group A and on 65-keV images of
      Group B were 11% and 21% higher than 65-keV images of Group A, respectively.
      CONCLUSIONS: Low-voltage CT simulated by VM image improved contrast enhancement
      through any phases, while high-concentration contrast material increased only
      arterial contrast in EAP more effectively.

PMID- 24891999
TI  - Dietary flounder skin improves growth performance, body composition, and stress
      recovery in the juvenile black rockfish (Sebastes schlegeli).
AB  - This study investigated the relationship between flounder skin meal (FSM) and
      vitamin C in mediating collagen biosynthesis. Based on the vitamin C requirements
      (150 mg/kg) of the black rockfish (mean body weight 10.05 +/- 0.44 g), a vitamin
      C level of 400 mg/kg was selected, and 0, 5, 10, or 20% of the casein (purified
      proteins) in the diet was replaced with FSM. The feeding study was conducted for
      8 weeks by using 4 experimental groups. The FSM supplementation resulted in
      improvement in growth performance, decrease of body lipids. Furthermore, it
      elevated the HDL-cholesterol levels and total protein content, reduced blood
      lipids, and led to rapid recovery in stress, which confirm the functionality of
      FSM with high collagen content. 

PMID- 24892000
TI  - QoS-based management of biomedical wireless sensor networks for patient
      monitoring.
AB  - Biomedical wireless sensor networks are a key technology to support the
      development of new applications and services targeting patient monitoring, in
      particular, regarding data collection for medical diagnosis and continuous health
      assessment. However, due to the critical nature of medical applications, such
      networks have to satisfy demanding quality of service requirements, while
      guaranteeing high levels of confidence and reliability. Such goals are influenced
      by several factors, where the network topology, the limited throughput, and the
      characteristics and dynamics of the surrounding environment are of major
      importance. Harsh environments, as hospital facilities, can compromise the radio
      frequency communications and, consequently, the network's ability to provide the
      quality of service required by medical applications. Furthermore, the impact of
      such environments on the network's performance is hard to manage due to its
      random and unpredictable nature. Consequently, network planning and management,
      in general or step-down hospital units, is a very hard task. In such context,
      this work presents a quality of service based management tool to help healthcare
      professionals supervising the network's performance and to assist them managing
      the admission of new sensor nodes (i.e., patients to be monitored) to the
      biomedical wireless sensor network. The proposed solution proves to be a valuable
      tool both, to detect and classify potential harmful variations in the quality of
      service provided by the network, avoiding its degradation to levels where the
      biomedical signs would be useless; and to manage the admission of new patients to
      the network. 

PMID- 24892001
TI  - Magnetic resonance imaging features of breast cancer according to intrinsic
      subtypes: correlations with neoadjuvant chemotherapy effects.
AB  - PURPOSE: The purpose of this study was to evaluate the magnetic resonance imaging
      (MRI) features of breast cancer according to intrinsic subtypes and to
      investigate whether the MRI and immunohistochemical findings were related to
      neoadjuvant chemotherapy (NAC) effects. MATERIALS AND METHODS: The MRI in 116
      women with breast cancers who underwent NAC was reviewed. The mass margin,
      presence of intratumoral necrosis, tumor extension around the mass, relative
      signal enhancement (RSE), and kinetic curve pattern were analyzed. We
      investigated the possible correlations between MRI findings and the effects of
      NAC. RESULTS: An irregular mass margin was significantly associated with luminal
      A cancers, while a smooth mass margin was associated with human epidermal growth
      factor receptor2 (HER2) cancers. Intratumoral necrosis was significantly
      associated with triple-negative cancers. Tumor extension around the mass was
      significantly infrequent in luminal-B cancers and frequent in HER2 cancers.
      Luminal-B and HER2 cancers showed a significantly higher RSE at 2 min than
      Luminal-A cancers. Estrogen receptor (ER)-positive cancers, HER2-negative
      cancers, and presence of intratumoral necrosis were significantly associated with
      the NAC non-response. CONCLUSIONS: Several MR features can be used to predict the
      intrinsic subtype of breast cancers. ER-positivity, HER2-negativity, and presence
      of intratumoral necrosis were significantly associated with NAC non-response.

PMID- 24892002
TI  - Analysis of dose measurement other than the radiation protection during the
      radiographic examination.
AB  - OBJECTIVES: The study measured the dose on body regions that were not shielded to
      protect from radiation exposure during the general procedure, with the goal of
      providing basic radiation dose data for radiological technologists who perform
      the radiographic examination. MATERIALS AND METHODS: Shooting parts with the
      phantom were similar to human tissues using general shooting equipment in the
      general examination room. The scattered rays were measured with the ion chamber.
      The hand received the highest average radiation dose and the kidney the lowest.
      The same pattern was evident for the average equivalent dose. The available daily
      shooting was highest in the anterior/posterior skull, followed by the
      posterior/anterior chest, abdomen, anterior/posterior spine and extremities.
      RESULTS: The daily available numbers for the eye were lower than other body
      regions (6-times, 4-times, 26-times, 3-times and 121-times) and the numbers on
      the foot were higher than for other regions (73-times, 48-times, 263-times, 39
      times and 702-times). CONCLUSIONS: Radiation should be thoroughly blocked by the
      apron to protect the radiological technologist from the radiation exposure, the
      proper distance from the irradiation source should be maintained exposure is
      inevitable and the exposure dose and working environment shall be regularly
      assessed to ensure minimal exposure dose of the radiological technologist in
      accordance with the International Commission on Radiological Protection
      recommendation.

PMID- 24892003
TI  - Longitudinal changes in insulin sensitivity, insulin secretion, beta cell
      function and glucose effectiveness during development of non-diabetic
      hyperglycemia in a Japanese population.
AB  - Since there had been no previous studies of alterations in insulin sensitivity,
      glucose-stimulated insulin secretion, beta cell function and glucose
      effectiveness during the development of non-diabetic hyperglycemia in Asian
      populations, we conducted a longitudinal study of such changes in 244 Japanese
      adults with normal glucose tolerance (median BMI 23.3 kg/m(2) and age 51 yrs).
      The median follow-up period was 3.3 yrs. One hundred and eighty-two subjects
      maintained normal glucose tolerance (nonprogressors). After excluding the 3
      subjects who progressed to diabetes, we analyzed the 59 who developed non
      diabetic hyperglycemia (progressors), of which 31 progressed to impaired fasting
      glucose and 28 to impaired glucose tolerance. Whole body insulin sensitivity was
      estimated by ISIMatsuda, glucose-stimulated insulin secretion by [deltaIRI0
      30/deltaPG0-30] and Stumvoll indices, hepatic insulin sensitivity by quantitative
      insulin sensitivity check index (QUICKI) and 1/fasting IRI, beta cell function by
      oral disposition index (DIO) ([deltaIRI0-30/deltaPG0-30]?[ISIMatsuda]), and
      glucose effectiveness by an OGTT-derived index (SgIO). ISIMatsuda (p <0.05),
      [deltaIRI0-30/deltaPG0-30], DIO and SgIO (both p <0.01), but not QUICKI,
      1/fasting IRI, or Stumvoll-1st and -2nd phases, were lower in the progressors at
      baseline. This group was also characterized by the following: 1) ISIMatsuda, DIO
      and SgIO were reduced by 34%, 32% and 11%, respectively (all p <0.01); 2) QUICKI
      and 1/fasting IRI diminished by 21% and 5%, respectively (both p <0.01); and 3)
      no significant changes were found in [deltaIRI0-30/deltaPG0-30], Stumvoll-1st and
      -2nd phases or BMI during the follow-up. In the nonprogressors, no indices
      changed significantly during the follow-up. Our study concluded that during the
      transition from normal glucose tolerance to non-diabetic hyperglycemia in this
      non-obese population, whole body insulin sensitivity, hepatic insulin
      sensitivity, beta cell function, and glucose effectiveness were all attenuated,
      but no significant changes in glucose-stimulated insulin secretion occurred. Also
      of note is the fact that the transition took place without any accompanying
      increase in BMI. 

PMID- 24892004
TI  - Inhibition of neutral sphingomyelinases in skeletal muscle attenuates fatty-acid
      induced defects in metabolism and stress.
AB  - BACKGROUND: Chronic metabolic overload leads to insulin resistance in a variety
      of tissues. It has been shown that exposure to saturated fatty acid palmitate can
      cause insulin resistance in skeletal muscle cells. Fatty acid induced synthesis
      of ceramide is considered to be one of the major causes for insulin resistance.
      Both de novo synthesis and sphingomyelin hydrolysis by sphingomyelinase are
      implicated for ceramide generation. Aim of this study was to evaluate the impact
      of neutral sphingomyelinase (nSMase) inhibition on saturated fatty acid induced
      lipotoxicity and insulin resistance in skeletal muscle myotubes. RESULTS:
      Treatment of saturated fatty acid (palmitate) but not unsaturated fatty acid
      (oleate) caused an up-regulation in expression of various nSMase genes which are
      associated with ceramide synthesis through the salvage pathway. Inhibition of
      nSMase by a pharmacological inhibitor (GW4869) partially reverted the palmitate
      induced insulin resistance in C2C12 myotubes. Inhibition of nSMase improved
      metabolic functions of myotubes as measured by improved oxidative capacity in
      terms of increased mitochondrial number, PGC1alpha expression and ATP levels with
      concomitant decrease in intramyocellular triglyceride levels. Palmitate induced
      inflammatory response was also reduced by nSMase inhibitor. GW4869 treatment
      reduced palmitate induced oxidative and endoplasmic reticulum stress and improved
      cell survival. CONCLUSION: In this study, we provide evidences that inhibition of
      nSMase can protect skeletal muscles from saturated fatty acid induced insulin
      resistance, metabolic dysfunction, cellular stress and inflammation.

PMID- 24892006
TI  - Intramural tracheal bronchogenic cyst: a case report.
AB  - Intramural bronchogenic cysts are extremely rare. We describe the case of an
      intramural bronchogenic cyst in a 2 year old boy who underwent tracheal resection
      and end-to-end anastomosis. 

PMID- 24892005
TI  - Pre- and postoperative alcohol consumption in breast cancer patients: impact on
      early events.
AB  - PURPOSE: To investigate the association between pre- and postoperative alcohol
      consumption and risk for early breast cancer events, since the association
      between alcohol consumption and prognosis in breast cancer patients is unclear.
      METHODS: Alcohol consumption was recorded for 934 primary breast cancer patients
      who underwent breast cancer surgery in Lund, Sweden, between 2002 and 2011 and
      were followed until December 31(st) 2012. Clinical data were obtained from
      medical records and population registries. Pre- and postoperative alcohol
      consumption was analyzed in relation to risk for early events. RESULTS: Median
      follow-up time was 3.03 years and 100 breast cancer events, 65 distant
      metastases, and 76 deaths occurred. Compared to no consumption, any preoperative
      alcohol consumption was weakly associated with lower risk for early events,
      adjusted HR 0.69 (0.45-1.04), distant metastases, 0.60 (0.36-1.00) and death,
      0.62 (0.38-1.01). In the 572 patients without axillary lymph node involvement,
      any alcohol consumption was not associated with risk for early events. However,
      in the 360 patients with axillary lymph node involvement, preoperative alcohol
      consumption was associated with lower risk for early events (adjusted HR 0.43
      0.24-0.77; P interaction = 0.01). CONCLUSION: Pre- and postoperative alcohol
      consumption was weakly associated with lower risk for early breast cancer events.
      The data does not support recommending that all breast cancer patients abstain
      from low to moderate alcohol consumption.

PMID- 24892009
TI  - Arthroscopic preparation and internal fixation of an unstable osteochondritis
      dissecans lesion of the knee.
AB  - We present our arthroscopic technique for fixation of an unstable osteochondritis
      dissecans (OCD) lesion. This technique includes arthroscopic evaluation of
      cartilage and bone quality of the OCD fragment, hinging open the lesion,
      debridement of fibrous nonunion tissue, reducing the fragment, and obtaining
      multi-point compression screw fixation. This technique avoids the morbidity of an
      open arthrotomy and should be considered when treating an unstable OCD lesion
      with adequate bone for fixation. 

PMID- 24892007
TI  - Enteroaggregative coli: A Pathogen Bridging the North and South.
AB  - Enteroaggregative Escherichia coli (EAEC) is a heterogeneous emerging enteric
      pathogen. Identified during the 1980's when EAEC strains where isolated from
      cases of acute and persistent diarrhea among infants from developing countries
      and of traveler's diarrhea. Subsequently, EAEC strains were linked with foodborne
      outbreaks and diarrhea illness in adults and children from industrialized
      countries, HIV-infected subjects and stunting of malnourished poor children.
      Nowadays, EAEC is increasingly recognized as a major cause of acute diarrhea in
      children recurring hospitalization and of traveler's diarrhea worldwide. EAEC
      strains defining phenotype is the aggregative adherence (AA) pattern on
      epithelial cells. AggR a transcriptional regulator of several EAEC virulence
      genes has been a key factor in both understanding EAEC pathogenesis and defining
      typical EAEC (tEAEC) strains. EAEC virulence genes distribution among these
      strains is highly variable. Present challenges are the identification of key
      virulence genes and how they coordinately function in the setting of enteric
      disease.

PMID- 24892010
TI  - Endoscopic Surgery for Symptomatic Unicameral Bone Cyst of the Proximal Femur.
AB  - Recently, surgical treatment of a symptomatic unicameral cyst of the proximal
      femur has been achieved with less invasive procedures than traditional open
      curettage with an autologous bone graft. In this article we introduce endoscopic
      surgery for a symptomatic unicameral cyst of the proximal femur. The presented
      technique, which includes minimally invasive endoscopic curettage of the cyst and
      injection of a bone substitute, not only minimizes muscle damage around the femur
      but also enables sufficient curettage of the fibrous membrane in the cyst wall
      and the bony septum through direct detailed visualization by an endoscope.
      Furthermore, sufficient initial strength after curettage can be obtained by
      injecting calcium phosphate cement as a bone substitute. 

PMID- 24892008
TI  - Managing Chronic Pain in Patients with Opioid Dependence.

PMID- 24892011
TI  - Arthroscopic posterior bone block procedure: a new technique using suture anchor
      fixation.
AB  - We present a novel all-arthroscopic technique of posterior shoulder stabilization
      that uses suture anchors for both bone block fixation and capsulolabral repair.
      The bone graft, introduced inside the glenohumeral joint through a cannula, is
      fixed with 2 suture anchors. The associated posteroinferior capsulolabral repair
      places the bone block in an extra-articular position. In this article we present
      the detailed arthroscopic technique performed in a consecutive series of 15
      patients and report the early results. We also report the positioning, healing,
      and remodeling of the bone block using postoperative 3-dimensional computed
      tomography. The benefits of this new technique are as follows: (1) it is all
      arthroscopic, preserving the posterior deltoid and posterior rotator cuff
      muscles; (2) it is accurate, resulting in appropriate bone block positioning; (3)
      it is efficient, allowing for consistent bone graft healing; (4) it is anatomic,
      both restoring the glenoid bone stock and repairing the injured posterior labrum;
      and (5) it is safe, limiting hardware-related complications and eliminating the
      risk of injury to vital structures associated with drilling or screw insertion
      from posterior to anterior. We believe that this technique is advantageous
      because it does not use screws for fixation and may be safer for the patient. 

PMID- 24892012
TI  - Arthroscopic lateral meniscus root repair with soft suture anchor technique.
AB  - Meniscus root tear leads to circumferential hoop tension loss and increases
      femorotibial contact force, which causes irreversible cartilage degeneration.
      Biomechanical studies have shown that meniscus root repair provides better
      femorotibial contact force than meniscectomy. Many techniques for meniscus root
      repair have been published in recent years. The soft suture anchor is widely used
      in the glenoid labral repair. It is a small low-profile soft anchor. This article
      presents a new and simple technique of lateral meniscus root repair using the
      small soft anchor, which results in an anatomic and more vertical anchor
      position. It avoids instrument-related complications, such as cartilage
      delamination, material reaction, metal retention, and hard suture anchor pullout.

PMID- 24892013
TI  - Physeal-sparing technique for femoral tunnel drilling in pediatric anterior
      cruciate ligament reconstruction using a posteromedial portal.
AB  - Pediatric anterior cruciate ligament (ACL) tears present a technical dilemma for
      orthopaedic surgeons. Multiple surgical techniques have been described to protect
      the distal femoral and proximal tibial physes. We present an ACL reconstruction
      technique performed on a 12-year-old girl with open physes who sustained an ACL
      tear after a noncontact twisting injury while playing soccer. A hamstring
      autograft reconstruction was performed by use of a posteromedial portal to drill
      the femoral tunnel in an all-epiphyseal fashion at the anatomic footprint of the
      native ACL. This case provides a new surgical technique to achieve anatomic
      fixation for ACL reconstruction in a skeletally immature individual using a
      posteromedial portal to drill a physeal-sparing lateral femoral tunnel for
      anatomic ACL reconstruction. This advancement may make drilling the femoral
      tunnel less technically challenging compared with other proposed methods while
      maintaining the lateral wall of the distal femur. 

PMID- 24892014
TI  - Medial patellofemoral ligament reconstruction procedure using a suspensory
      femoral fixation system.
AB  - Recurrent patellar dislocation has recently been treated with anatomic medial
      patellofemoral ligament (MPFL) reconstruction using a semitendinosus muscle
      tendon. Although it is necessary to add tension to fix the tendon graft without
      loading excess stress on the patellofemoral joint, adjustment of the tension can
      be difficult. To resolve this problem, we developed an MPFL reconstruction
      procedure using the ToggleLoc Fixation Device (Biomet, Warsaw, IN), in which the
      semitendinosus muscle tendon is folded and used as a double-bundle tendon graft
      and 2 bone tunnels and 1 bone tunnel are made on the patellar and femoral sides,
      respectively. The patellar side of the tendon graft is fixed with an EndoButton
      (Smith & Nephew, London, England), and the femoral side is fixed with the
      ToggleLoc. Stepless adjustment of tension of the tendon graft is possible by
      reducing the size of the loop of the ToggleLoc hung onto the tendon graft. It may
      be useful to position the patella in the center of the femoral sulcus by
      confirming the patellofemoral joint fitting. Stability can be confirmed by
      loading lateral stress on the patella in the extended knee joint. This procedure
      is less invasive because opening of the lateral side of the femur is not
      necessary, and it may be useful for MPFL reconstruction. 

PMID- 24892015
TI  - Basic knee arthroscopy part 1: patient positioning.
AB  - Knee arthroscopy is an important diagnostic and therapeutic tool in the
      management of disorders of the knee. In a series of 4 articles, the basics of
      knee arthroscopy are reviewed. In this article (part 1), patient positioning,
      tourniquet placement, and draping are reviewed. Meticulous attention to these
      details allows surgical access to the compartments of the knee. A circumferential
      leg holder or a lateral post allows the application of varus and valgus forces to
      open the medial and lateral compartments of the knee. 

PMID- 24892016
TI  - Basic knee arthroscopy part 2: surface anatomy and portal placement.
AB  - Knee arthroscopy is an important diagnostic and therapeutic tool in the
      management of disorders of the knee. In a series of 4 articles, the basics of
      knee arthroscopy are reviewed. In this article (part 2), surface anatomy and the
      anterolateral and anteromedial portals are reviewed. Accurate portal placement is
      critical to both diagnostic and operative arthroscopy. Mastery of the surface
      anatomy allows accurate and reproducible portal placement. 

PMID- 24892017
TI  - Basic knee arthroscopy part 3: diagnostic arthroscopy.
AB  - Knee arthroscopy is an important diagnostic and therapeutic tool in the
      management of disorders of the knee. In a series of 4 articles, the basics of
      knee arthroscopy are reviewed. In this article (part 3), step-by-step diagnostic
      arthroscopy is reviewed. Diagnostic arthroscopy is a crucial skill for diagnosing
      intra-articular disorders of the knee including meniscal, synovial, ligamentous,
      and articular cartilage pathology. Mastery of the basic diagnostic arthroscopy is
      a critical tool for orthopaedic surgeons treating disorders of the knee. 

PMID- 24892018
TI  - Basic knee arthroscopy part 4: chondroplasty, meniscectomy, and cruciate ligament
      evaluation.
AB  - Knee arthroscopy is an important diagnostic and therapeutic tool in the
      management of disorders of the knee. In a series of 4 articles, the basics of
      knee arthroscopy are reviewed. In this article (part 4), the basics of operative
      knee arthroscopy are reviewed including chondroplasty and meniscectomy.
      Evaluation of the cruciate ligaments is also reviewed. Mastery of these
      techniques is critical for the treatment of the most common pathology encountered
      during knee arthroscopy. 

PMID- 24892019
TI  - Metabolic theory of septic shock.
AB  - Septic shock is a life threatening condition that can develop subsequent to
      infection. Mortality can reach as high as 80% with over 150000 deaths yearly in
      the United States alone. Septic shock causes progressive failure of vital
      homeostatic mechanisms culminating in immunosuppression, coagulopathy and
      microvascular dysfunction which can lead to refractory hypotension, organ failure
      and death. The hypermetabolic response that accompanies a systemic inflammatory
      reaction places high demands upon stored nutritional resources. A crucial element
      that can become depleted early during the progression to septic shock is
      glutathione. Glutathione is chiefly responsible for supplying reducing
      equivalents to neutralize hydrogen peroxide, a toxic oxidizing agent that is
      produced during normal metabolism. Without glutathione, hydrogen peroxide can
      rise to toxic levels in tissues and blood where it can cause severe oxidative
      injury to organs and to the microvasculature. Continued exposure can result in
      microvascular dysfunction, capillary leakage and septic shock. It is the aim of
      this paper to present evidence that elevated systemic levels of hydrogen peroxide
      are present in septic shock victims and that it significantly contributes to the
      development and progression of this frequently lethal condition. 

PMID- 24892022
TI  - Reader's Forum.

PMID- 24892020
TI  - Arterial vs venous blood gas differences during hemorrhagic shock.
AB  - AIM: To characterize differences of arterial (ABG) and venous (VBG) blood gas
      analysis in a rabbit model of hemorrhagic shock. METHODS: Following baseline
      arterial and venous blood gas analysis, fifty anesthetized, ventilated New
      Zealand white rabbits were hemorrhaged to and maintained at a mean arterial
      pressure of 40 mmHg until a state of shock was obtained, as defined by arterial
      pH <= 7.2 and base deficit <= -15 mmol/L. Simultaneous ABG and VBG were obtained
      at 3 minute intervals. Comparisons of pH, base deficit, pCO2, and arteriovenous
      (a-v) differences were then made between ABG and VBG at baseline and shock
      states. Statistical analysis was applied where appropriate with a significance of
      P < 0.05. RESULTS: All 50 animals were hemorrhaged to shock status and
      euthanized; no unexpected loss occurred. Significant differences were noted
      between baseline and shock states in blood gases for the following parameters: pH
      was significantly decreased in both arterial (7.39 +/- 0.12 to 7.14 +/- 0.18) and
      venous blood gases (7.35 +/- 0.15 to 6.98 +/- 0.26, P < 0.05), base deficit was
      significantly increased for arterial (-0.9 +/- 3.9 mEq/L vs -17.8 +/- 2.2 mEq/L)
      and venous blood gasses (-0.8 +/- 3.8 mEq/L vs -15.3 +/- 4.1 mEq/L, P < 0.05).
      pCO2 trends (baseline to shock) demonstrated a decrease in arterial blood (40.0
      +/- 9.1 mmHg vs 28.9 +/- 7.1 mmHg) but an increase in venous blood (46.0 +/- 10.1
      mmHg vs 62.8 +/- 15.3 mmHg), although these trends were non-significant. For
      calculated arteriovenous differences between baseline and shock states, only the
      pCO2 difference was shown to be significant during shock. CONCLUSION: In this
      rabbit model, significant differences exist in blood gas measurements for
      arterial and venous blood after hemorrhagic shock. A widened pCO2 a-v difference
      during hemorrhage, reflective of poor tissue oxygenation, may be a better
      indicator of impending shock.

PMID- 24892021
TI  - Variable change in renal function by hypertonic saline.
AB  - AIM: To investigate the effects of hypertonic saline in the neurocritical care
      population. METHODS: We retrospectively reviewed our hospital's use of hypertonic
      saline (HS) since March of 2005, and prospectively since October 2010.
      Comparisons were made between admission diagnoses, creatinine change (Cr), and HS
      formulation (3% NaCl, 3% NaCl/sodium acetate mix, and 23.4% NaCl) to patients
      receiving normal saline or lactated ringers. The patients (n = 1329) of the
      retrospective portion were identified. The data presented represents the first
      230 patients with data. RESULTS: Significant differences in Acute Physiology and
      Chronic Health Evaluation II scores and Glasgow Coma Scale scores occurred
      between different saline formulations. No significant correlation of Cl(-) or
      Na(+) with Cr, nor with saline types, occurred. When dichotomized by diagnosis,
      significant correlations appear. Traumatic brain injury (TBI) patients
      demonstrated moderate correlation between Na(+) and Cr of 0.45. Stroke patients
      demonstrated weak correlations between Na(+) and Cr, and Cl(-) and Cr (0.19 for
      both). Patients receiving HS and not diagnosed with intracerebral hemorrhage,
      stroke, subarachnoid hemorrhage, or TBI demonstrated a weak but significant
      correlation between Cl(-) and Cr at 0.29. CONCLUSION: Cr directly correlates with
      Na(+) or Cl(-) in stroke, Na(+) in TBI, and Cl(-) in other populations.
      Prospective comparison of HS and renal function is needed.

PMID- 24892023
TI  - Effect of silica coating on bond strength between a gold alloy and metal bracket
      bonded with chemically cured resin.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of three
      different surface conditioning methods on the shear bond strength (SBS) of metal
      brackets bonded directly to gold alloy with chemically cured resin. METHODS: Two
      hundred ten type III gold alloy specimens were randomly divided into six groups
      according to the combination of three different surface conditioning methods
      (aluminum oxide sandblasting only, application of a metal primer after aluminum
      oxide sandblasting, silica coating and silanation) and thermocycling (with
      thermocycling, without thermocycling). After performing surface conditioning of
      specimens in accordance with each experimental condition, metal brackets were
      bonded to all specimens using a chemically cured resin. The SBS was measured at
      the moment of bracket debonding, and the resin remnants on the specimen surface
      were evaluated using the adhesive remnant index. RESULTS: Application of metal
      primer after aluminum oxide sandblasting yielded a higher bond strength than that
      with aluminum oxide sandblasting alone (p < 0.001), and silica coating and
      silanation yielded a higher bond strength than that with metal primer after
      aluminum oxide sandblasting (p < 0.001). There was no significant change in SBS
      after thermocycling in all groups. CONCLUSIONS: With silica coating and
      silanation, clinically satisfactory bond strength can be attained when metal
      brackets are directly bonded to gold alloys using a chemically cured resin.

PMID- 24892024
TI  - Effects of various toothpastes on remineralization of white spot lesions.
AB  - OBJECTIVE: The purpose of this in vitro study was to examine the effects of
      fluoridated, casein phosphopeptide.amorphous calcium phosphate complex (CPP-ACP)
      containing, and functionalized beta-tricalcium phosphate (fTCP)-containing
      toothpastes on remineralization of white spot lesions (WSLs) by using
      Quantitative light-induced fluorescence (QLF-D) BiluminatorTM 2. METHODS: Forty
      eight premolars, extracted for orthodontic reasons from 12 patients, with
      artificially induced WSLs were randomly and equally assigned to four treatment
      groups: fluoride (1,000 ppm), CPP-ACP, fTCP (with sodium fluoride), and control
      (deionized water) groups. Specimens were treated twice daily for 2 weeks and
      stored in saliva solution (1:1 mixture of artificial and human stimulated saliva)
      otherwise. QLF-D BiluminatorTM 2 was used to measure changes in fluorescence,
      indicating alterations in the mineral contents of the WSLs, immediately before
      and after the 2 weeks of treatment. RESULTS: Fluorescence greatly increased in
      the fTCP and CPP-ACP groups compared with the fluoride and control groups, which
      did not show significant differences. CONCLUSIONS: fTCP- and CPP-ACP-containing
      toothpastes seem to be more effective in reducing WSLs than 1,000-ppm fluoride
      containing toothpastes.

PMID- 24892025
TI  - Long-term stability of dentoalveolar, skeletal, and soft tissue changes after non
      extraction treatment with a self-ligating system.
AB  - OBJECTIVE: To evaluate the long-term effects of self-ligating brackets (SLBs) on
      transverse dimensions of arches and skeletal and soft tissues and to
      quantitatively evaluate the treatment outcome after non-extraction treatment with
      SLBs. METHODS: The sample consisted of 24 (18 female and six male) subjects, with
      a mean age of 14.23 +/- 2.19 years, who received treatment with the Damon(r)3
      appliances. Complete records including cephalometric radiographs and plaster
      models were obtained before treatment (T1), immediately after treatment (T2), six
      months after treatment (T3), and two years (T4) after treatment. Digital study
      models were generated. Twenty lateral cephalometric, six frontal cephalometric,
      and eight dental cast measurements were examined. The Peer Assessment Rating
      index was used to measure the treatment outcome. The Wilcoxon test was applied
      for statistical analysis of the changes. RESULTS: There were significant
      increases in all transverse dental cast measurements with active treatment. There
      was some significant relapse in the long term, particularly in maxillary width (p
      < 0.05). Statistically significant increases were found in nasal (p < 0.001),
      maxillary base, upper molar, lower intercanine, and antigonial (p < 0.05) widths
      in T1-T2. Lower incisors were proclined and protruded in T1-T2. CONCLUSIONS: SLBs
      correct crowding by mechanisms involving incisor proclination and protrusion and
      expansion of the dental arches, without induction of clinically significant
      changes in hard and soft tissues of the face.

PMID- 24892026
TI  - Evaluation of the genotoxicity and cytotoxicity in the buccal epithelial cells of
      patients undergoing orthodontic treatment with three light-cured bonding
      composites by using micronucleus testing.
AB  - OBJECTIVE: This study evaluated the cytotoxicity and genotoxicity of fixed
      orthodontic treatment with three different light-cured orthodontic bonding
      composites by analyzing micronucleus (MN) formation in the buccal mucosa during a
      6-month period. METHODS: Thirty healthy volunteers were selected from consecutive
      patients referred for orthodontic treatment. Equilibrium 2 brackets and molar
      tubes (Dentaurum) were bonded with three different light-cured orthodontic
      bonding composites-Transbond XT (3M Unitek), Kurasper F (Kuraray Europe), or
      GrenGloo (Ormco Corporation)- to all teeth in both arches. Exfoliated buccal
      epithelial cells were scraped from the middle part of the inner cheeks with
      sterile cement spatulas before treatment and at 1, 3, and 6 months after
      treatment. MNs and nuclear alterations, such as karyorrhexis (KR), karyolysis
      (KL), and binucleated cells (BNs), were scored under a light microscope. Repeated
      measure ANOVA was used to calculate statistical differences in degenerative
      nuclear abnormalities. RESULTS: MN rates did not significantly differ among
      different time points within the same cell type (p > 0.05). In contrast, the
      number of BNs in buccal epithelial cells significantly increased in all composite
      groups (p < 0.01, Transbond XT; p < 0.001, Kurasper F and GrenGloo). KL frequency
      significantly increased between the beginning and end of the study in the
      Kurasfer F (0.80 +/- 0.79 to 1.90 +/- 1.10; p < 0.05) and GrenGloo (1.30 +/- 1.06
      to 2.40 +/- 1.08; p < 0.05) groups. CONCLUSIONS: After 6 months of fixed
      orthodontic treatment with different light-cured composites, morphological signs
      of cytotoxicity were observed but genotoxic effects were absent.

PMID- 24892027
TI  - Active-treatment effects of the Forsus fatigue resistant device during
      comprehensive Class II correction in growing patients.
AB  - OBJECTIVE: To evaluate the active-treatment effects of the Forsus fatigue
      resistant device (Forsus) during comprehensive correction of Class II
      malocclusion in growing patients. METHODS: Fifty-four patients (mean age, 12.5 +/
      1.2 years) with Class II division 1 malocclusion were consecutively treated with
      fixed app-liances in combination with Forsus. Lateral cephalograms were analyzed
      at the beginning of the fixed treatment (T1), Forsus insertion (T2), its removal
      (T3), and end of the comprehensive therapy (T4). Statistical comparisons were
      carried out by repeated-measures ANOVA with Tukey's post-hoc test (p < 0.05).
      RESULTS: The overall therapeutic effects were mainly dentoalveolar and occurred
      mostly during the active treatment with Forsus (T2-T3, mean duration = 0.5 +/-
      0.1 years). The overjet and overbite decreased significantly (-3.5 and -1.5 mm,
      respectively) and the molar relationship improved by 4.3 mm. These changes were
      associated with significant retroclination of the maxillary incisors (-3.1
      degrees ), proclination and intrusion of the mandibular incisors (+5.0 degrees 
      and -1.5 mm, respectively), and mesialization of the mandibular molars (+2.0 mm).
      CONCLUSIONS: Forsus had mainly dentoalveolar effects and contributed largely to
      the overall therapeutic outcome.

PMID- 24892028
TI  - Functional evaluation of orthopedic and orthodontic treatment in a patient with
      unilateral posterior crossbite and facial asymmetry.
AB  - An 8-years old boy with facial asymmetry and unilateral posterior crossbite on
      the left side received orthopedic and orthodontic treatment. During the first
      phase of treatment, the narrow maxillary arch was expanded using an acrylic
      plate. Then, the acrylic plate was used as a bite block with occlusal
      indentations from the construction bite that was obtained with the incisors in a
      coincident dental midline. After the position of the mandible was stabilized, the
      second phase of orthodontic treatment was initiated using fixed appliances for
      detailing of the occlusion. Skeletal symmetry, ideal occlusion, and coincident
      dental midlines were thus achieved. Functionally, occlusal force balance and
      masticatory muscle activity were improved, and the chewing patterns were
      normalized. 

PMID- 24892030
TI  - IL-8 secretion in primary cultures of prostate cells is associated with prostate
      cancer aggressiveness.
AB  - BACKGROUND: Chronic inflammation is believed to be a major factor in prostate
      cancer initiation and promotion and has been studied using prostate cancer cells
      and immortalized cell lines. However, little is known about the contribution of
      normal cells to the prostatic microenvironment and inflammation. We aim to study
      the contribution of normal prostate epithelial cells to prostate inflammation and
      to link the inflammatory status of normal cells to prostate cancer
      aggressiveness. MATERIALS AND METHODS: Short-term primary cell cultures of normal
      epithelial prostate cells were derived from prostate biopsies from 25 men
      undergoing radical prostatectomy, cystoprostatectomy, or organ donation. Cells
      were treated with polyinosinic:polycytidylic acid, a mimic of double-stranded
      viral RNA and a potent inducer of the inflammatory response. Secretion of
      interleukin (IL)-8 in the cell culture medium by untreated and treated cells was
      measured and we determined the association between IL-8 levels in these primary
      cell cultures and prostate cancer characteristics. The Fligner-Policello test was
      used to compare the groups. RESULTS: Baseline and induced IL-8 secretion were
      highly variable between cultured cells from different patients. This variation
      was not related to drug use, past medical history, age, or preoperative prostate
      specific antigen value. Nonetheless, an elevated secretion of IL-8 from normal
      cultured epithelial cells was associated with prostate cancer aggressiveness
      (P=0.0005). CONCLUSION: The baseline secretion of IL-8 from normal prostate
      epithelial cells in culture is strongly correlated with cancer aggressiveness and
      may drive prostate cancer carcinogenesis. A better characterization of individual
      prostate microenvironment may provide a basis for personalized treatment and for
      monitoring the effects of strategies aimed at preventing aggressive prostate
      cancer.

PMID- 24892029
TI  - Long-term effects of pediatric extracorporeal shockwave lithotripsy on renal
      function.
AB  - INTRODUCTION: Extracorporeal shock wave lithotripsy (ESWL) is a well-known and
      successful treatment modality. In addition, it can be used in premature infants.
      ESWL is used to treat kidney and ureter stones in children. However, although it
      is a preferred noninvasive treatment in that setting, there is debate about its
      long-term effects on growing kidneys in children. OBJECTIVES: To investigate the
      long-term effects of pediatric ESWL on renal function in light of updated
      literature. METHODS: PubMed and Medline were searched for studies on ESWL in a
      pediatric population with keywords including efficacy, child, kidney calculi,
      ureter calculi, lithotripsy, injury, vascular trauma, and shock waves. The
      research was limited to the English literature during a period from 1980 to 2014.
      In total, 3,000 articles were evaluated, but only 151 papers were considered.
      Only the manuscripts directly related to the reviewed subjects were included in
      the current study. RESULTS: However, the acute effects of ESWL in kidney are well
      described. Although there are limited studies on the long-term effects of ESWL in
      children, there is a widespread opinion that ESWL is not affecting renal
      functions in the long-term. CONCLUSION: ESWL is a safe, effective, and
      noninvasive treatment option in children. Although ESWL can cause some acute
      effects in the kidney, there is no long-term effect on the growing kidneys of
      children.

PMID- 24892031
TI  - Post-prostatectomy erectile dysfunction: contemporary approaches from a US
      perspective.
AB  - Success of cancer surgery often leads to life-changing side effects, and surgical
      treatment for malignant urologic disease often results in erectile dysfunction
      (ED). Patients that undergo surgical prostatectomy or cystoprostatectomy will
      often experience impairment of erections due to disruption of blood and nerve
      supply. Surgical technique, nerve sparing status, patient age, comorbid
      conditions, and pretreatment potency status all have an effect on post-surgical
      ED. Regardless of surgical technique, prostatectomy results in disruption of
      normal anatomy and nerve supply to the penis, which governs the functional
      aspects of erection. A variety of different treatment options are available for
      men who develop ED after prostatectomy, including vacuum erection device, oral
      phosphodiesterase 5 inhibitors (PDE5I), intracorporal injections, and penile
      prosthesis. The vacuum erection device creates an artificial erection by forming
      a vacuum via suction of air to draw blood into the penis. The majority of men
      using the vacuum erection device daily after prostatectomy, regardless of nerve
      sparing status, have erections sufficient for intercourse. Phosphodiesterase 5
      inhibitors remain a common treatment option for post-surgical ED and are the
      mainstay of therapy. They work through cyclic adenosine monophosphate and cyclic
      guanine monophosphate pathways and are recommended in all forms of ED.
      Intracorporal injections or intraurethral use of vasoactive substances may be a
      good second-line therapy in men who do not experience improvement with oral
      medications. Surgical placement of a penile prosthesis is typically the treatment
      strategy of choice after other options have failed. Semi-rigid and inflatable
      devices are available with high satisfaction rates. With careful patient
      counseling and proper treatment selection, patient satisfaction and improved
      erectile function can be achieved. We advise that patients use a vacuum erection
      device daily in the early postoperative period in combination with an oral PDE5I.
      For patients who do not respond to a vacuum erection device or PDE5I,
      consideration should be given to intraurethral alprostadil, intracorporal
      injections, or a penile prosthesis. 

PMID- 24892032
TI  - Simultaneous laparoscopic management of ureteropelvic junction obstruction and
      renal lithiasis: the combined experience of two academic centers and review of
      the literature.
AB  - INTRODUCTION: Approximately one out of five patients with ureteropelvic junction
      obstruction (UPJO) present lithiasis in the same setting. We present our outcomes
      of simultaneous laparoscopic management of UPJO and pelvic or calyceal lithiasis
      and review the current literature. METHODS: Thirteen patients, with a mean age of
      42.8+/-13.3 years were diagnosed with UPJO and pelvic or calyceal lithiasis. All
      patients were subjected to laparoscopic dismembered Hynes-Anderson pyeloplasty
      along with removal of single or multiple stones, using a combination of
      laparoscopic graspers, irrigation, and flexible nephroscopy with nitinol baskets.
      RESULTS: The mean operative time was 218.8+/-66 minutes. In two cases,
      transposition of the ureter due to crossing vessels was performed. The mean
      diameter of the largest stone was 0.87+/-0.25 cm and the mean number of stones
      retrieved was 8.2 (1-32). Eleven out of 13 patients (84.6%) were rendered stone
      free. Complications included prolonged urine output from the drain in one case
      (Clavien grade I) and urinoma formation requiring drainage in another case
      (Clavien grade IIIa). The mean postoperative follow-up was 30.2 (7-51) months. No
      patient has experienced stone or UPJO recurrence. CONCLUSION: Laparoscopy for the
      management of UPJO along with renal stone removal seems a very appealing
      treatment, with all the advantages of minimally invasive surgery. Concomitant
      renal stones do not affect the outcome of laparoscopic pyeloplasty, at least in
      the midterm. According to our results and the latest literature data, we advocate
      laparoscopic management as the treatment of choice for these cases.

PMID- 24892033
TI  - Emerging treatments for overactive bladder: clinical potential of botulinum
      toxins.
AB  - Overactive bladder (OAB) is a symptom syndrome including urgency, frequency, and
      nocturia - with or without incontinence. It is a common manifestation of detrusor
      overactivity (DO). DO is a urodynamic observation of spontaneous or provoked
      contractions of the detrusor muscle is seen during the filling phase of the
      micturition cycle. OAB is, therefore, both a motor and sensory disorder.
      Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum
      and has been used in medicine for many years. Over the last 10 years, it has been
      used for the treatment of DO and OAB when standard treatments, such as bladder
      training and oral anticholinergic medication, have failed to provide symptom
      relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release
      from the neurons in the motor end plate and also at sensory synapses, although
      the clinical effect is not permanent due to the growth of new connections within
      treated tissues. It is known that botulinum toxin modulates vanillioid,
      purinergic, capsaicin, and muscarinic receptor expression within the lamina
      propria, returning them to levels seen in normal bladders. Clinically, the effect
      of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon
      the symptom of urgency, and also large effects on frequency, nocturia, leakage
      episodes, and continence rates. These effects have been seen consistently within
      eight randomized trials and numerous case series. Botulinum toxin appears safe,
      with the only common side effect being that of voiding difficulty, occurring in
      up to 10% of treated patients. Dosing regimens are variable, depending on which
      preparation is used, but it is clear that dose recommendations have fallen over
      the last 5 years. There is limited evidence about the efficacy of repeat
      treatments. Botulinum toxin is an effective and safe second-line treatment for
      patients with OAB and DO. 

PMID- 24892034
TI  - Gender differences in metabolic disorders and related diseases in Spontaneously
      Diabetic Torii-Lepr(fa) rats.
AB  - The Spontaneously Diabetic Torii Lepr(fa) (SDT fatty) rat is a novel type 2
      diabetic model wherein both male and female rats develop glucose and lipid
      abnormalities from a young age. In this study, we investigated gender differences
      in abnormalities and related complications in SDT fatty rats. Food intake was
      higher in males compared to female rats; however, body weight was not different
      between genders. Progression of diabetes, including increases in blood glucose
      and declines in blood insulin, was observed earlier in male rats than in females,
      and diabetic grade was more critical in male rats. Blood lipids tended to
      increase in female rats. Gonadal dysfunction was observed in both male and female
      rats with aging. Microangiopathies, such as nephropathy, retinopathy, neuropathy,
      and osteoporosis, were seen in both genders, and pathological grade and
      progression were more significant in males. Qualitative and quantitative changes
      were observed for metabolic disease gender differences in SDT fatty rats. The SDT
      fatty rat is a useful model for researching gender differences in metabolic
      disorders and related diseases in diabetes with obesity.

PMID- 24892037
TI  - CGE simulation analysis on the labor transfer, agricultural technical progress,
      and economic development in Chongqing.
AB  - The basic structure of a CGE model dividing Mainland China into two parts,
      including Chongqing and rest regions, is described. Based on this CGE model, both
      the unilateral impact and collaborative impact of two policies, agricultural
      technical progress and supporting policies for improving rural labor transfer on
      the economic development in Chongqing, are simulated and analyzed. The results
      demonstrate that compared with the sum of each unilateral policy effect, the
      collaboration of two policies has more effective impact on facilitating the labor
      transfer, promoting regional economic growth, and improving income and welfare of
      urban and rural residents. 

PMID- 24892035
TI  - Protection against experimental melioidosis following immunisation with a
      lipopolysaccharide-protein conjugate.
AB  - Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei.
      It is refractory to antibiotic treatment and there is currently no licensed
      vaccine. In this report we detail the construction and protective efficacy of a
      polysaccharide-protein conjugate composed of B. pseudomallei lipopolysaccharide
      and the Hc fragment of tetanus toxin. Immunisation of mice with the
      lipopolysaccharide-conjugate led to significantly reduced bacterial burdens in
      the spleen 48 hours after challenge and afforded significant protection against a
      lethal challenge with B. pseudomallei. The conjugate generated significantly
      higher levels of antigen-specific IgG1 and IgG2a than in lipopolysaccharide
      immunised mice. Immunisation with the conjugate also demonstrated a bias towards
      Th1 type responses, evidenced by high levels of IgG2a. In contrast, immunisation
      with unconjugated lipopolysaccharide evoked almost no IgG2a demonstrating a bias
      towards Th2 type responses. This study demonstrates the effectiveness of this
      approach in the development of an efficacious and protective vaccine against
      melioidosis. 

PMID- 24892036
TI  - Expression of Shelterin component POT1 is associated with decreased telomere
      length and immunity condition in humans with severe aplastic anemia.
AB  - Abnormal telomere attrition has been found to be closely related to patients with
      SAA in recent years. To identify the incidence of telomere attrition in SAA
      patients and investigate the relationship of telomere length with clinical
      parameters, SAA patients (n=27) and healthy controls (n=15) were enrolled in this
      study. Telomere length of PWBCs was significantly shorter in SAA patients than in
      controls. Analysis of gene expression of Shelterin complex revealed markedly low
      levels of POT1 expression in SAA groups relative to controls. No differences in
      the gene expression of the other Shelterin components-TRF1, TRF2, TIN2, TPP1, and
      RAP1-were identified. Addition of IFN-gamma to culture media induced a similar
      fall in POT1 expression in bone marrow cells to that observed in cells cultured
      in the presence of SAA serum, suggesting IFN-gamma is the agent responsible for
      this effect of SAA serum. Furthermore, ATR, phosphorylated ATR, and
      phosphorylated ATM/ATR substrate were all found similarly increased in bone
      marrow cells exposed to SAA serum, TNF-alpha, or IFN-gamma. In summary, SAA
      patients have short telomeres and decreased POT1 expression. TNF-alpha and IFN
      gamma are found at high concentrations in SAA patients and may be the effectors
      that trigger apoptosis through POT1 and ATR.

PMID- 24892038
TI  - A high-performance genetic algorithm: using traveling salesman problem as a case.
AB  - This paper presents a simple but efficient algorithm for reducing the computation
      time of genetic algorithm (GA) and its variants. The proposed algorithm is
      motivated by the observation that genes common to all the individuals of a GA
      have a high probability of surviving the evolution and ending up being part of
      the final solution; as such, they can be saved away to eliminate the redundant
      computations at the later generations of a GA. To evaluate the performance of the
      proposed algorithm, we use it not only to solve the traveling salesman problem
      but also to provide an extensive analysis on the impact it may have on the
      quality of the end result. Our experimental results indicate that the proposed
      algorithm can significantly reduce the computation time of GA and GA-based
      algorithms while limiting the degradation of the quality of the end result to a
      very small percentage compared to traditional GA. 

PMID- 24892039
TI  - Multiple-site hemodynamic analysis of Doppler ultrasound with an adaptive color
      relation classifier for arteriovenous access occlusion evaluation.
AB  - This study proposes multiple-site hemodynamic analysis of Doppler ultrasound with
      an adaptive color relation classifier for arteriovenous access occlusion
      evaluation in routine examinations. The hemodynamic analysis is used to express
      the properties of blood flow through a vital access or a tube, using
      dimensionless numbers. An acoustic measurement is carried out to detect the peak
      systolic and peak-diastolic velocities of blood flow from the arterial
      anastomosis sites (A) to the venous anastomosis sites (V). The ratio of the
      supracritical Reynolds (Re(supra)) number and the resistive (Res) index
      quantitates the degrees of stenosis (DOS) at multiple measurement sites. Then, an
      adaptive color relation classifier is designed as a nonlinear estimate model to
      survey the occlusion level in monthly examinations. For 30 long-term follow-up
      patients, the experimental results show the proposed screening model efficiently
      evaluates access occlusion.

PMID- 24892041
TI  - Identifiability and identification of trace continuous pollutant source.
AB  - Accidental pollution events often threaten people's health and lives, and a
      pollutant source is very necessary so that prompt remedial actions can be taken.
      In this paper, a trace continuous pollutant source identification method is
      developed to identify a sudden continuous emission pollutant source in an
      enclosed space. The location probability model is set up firstly, and then the
      identification method is realized by searching a global optimal objective value
      of the location probability. In order to discuss the identifiability performance
      of the presented method, a conception of a synergy degree of velocity fields is
      presented in order to quantitatively analyze the impact of velocity field on the
      identification performance. Based on this conception, some simulation cases were
      conducted. The application conditions of this method are obtained according to
      the simulation studies. In order to verify the presented method, we designed an
      experiment and identified an unknown source appearing in the experimental space.
      The result showed that the method can identify a sudden trace continuous source
      when the studied situation satisfies the application conditions. 

PMID- 24892040
TI  - Biomechanical considerations in the design of high-flexion total knee
      replacements.
AB  - Typically, joint arthroplasty is performed to relieve pain and improve
      functionality in a diseased or damaged joint. Total knee arthroplasty (TKA)
      involves replacing the entire knee joint, both femoral and tibial surfaces, with
      anatomically shaped artificial components in the hope of regaining normal joint
      function and permitting a full range of knee flexion. In spite of the design of
      the prosthesis itself, the degree of flexion attainable following TKA depends on
      a variety of factors, such as the joint's preoperative condition/flexion, muscle
      strength, and surgical technique. High-flexion knee prostheses have been
      developed to accommodate movements that require greater flexion than typically
      achievable with conventional TKA; such high flexion is especially prevalent in
      Asian cultures. Recently, computational techniques have been widely used for
      evaluating the functionality of knee prostheses and for improving biomechanical
      performance. To offer a better understanding of the development and evaluation
      techniques currently available, this paper aims to review some of the latest
      trends in the simulation of high-flexion knee prostheses. 

PMID- 24892043
TI  - Characterizing the effects of intermittent faults on a processor for
      dependability enhancement strategy.
AB  - As semiconductor technology scales into the nanometer regime, intermittent faults
      have become an increasing threat. This paper focuses on the effects of
      intermittent faults on NET versus REG on one hand and the implications for
      dependability strategy on the other. First, the vulnerability characteristics of
      representative units in OpenSPARC T2 are revealed, and in particular, the highly
      sensitive modules are identified. Second, an arch-level dependability enhancement
      strategy is proposed, showing that events such as core/strand running status and
      core-memory interface events can be candidates of detectable symptoms. A simple
      watchdog can be deployed to detect application running status (IEXE event). Then
      SDC (silent data corruption) rate is evaluated demonstrating its potential. Third
      and last, the effects of traditional protection schemes in the target CMT to
      intermittent faults are quantitatively studied on behalf of the contribution of
      each trap type, demonstrating the necessity of taking this factor into account
      for the strategy. 

PMID- 24892042
TI  - Alteration of cytokine profiles in uranium miners exposed to long-term low dose
      ionizing radiation.
AB  - OBJECTIVE: The aim of the study is to estimate the immune function through
      cytokine profiles in sera of uranium mines. METHODS: Antibody arrays were used to
      detect 50 cytokines in sera of uranium miners. Miners who had continuously worked
      underground for <5 years were treated as control group and those who worked for ?
      5 years as experimental group. RESULTS: Of 28 measurable cytokines, the release
      of IL-1 alpha , IL-1RI, IL-15, IL-3, and IP-10 were significantly upregulated in
      the experimental group, and no cytokine was found significantly downregulated.
      Other proinflammatory cytokines such as IFN-gamma, IL-10, IL-6, and TNF alpha
      levels were slightly upregulated in the experimental group. With adjustment to
      age, BMI, and cigarette smoking, IL-1 alpha and IL-3 levels increased
      significantly with underground time. CONCLUSION: Alteration of cytokine profiles
      in this study may indicate persistent inflammatory responses in uranium miners
      exposed to long-term low doses radiation.

PMID- 24892045
TI  - The lattices of group fuzzy congruences and normal fuzzy subsemigroups on E
      inversive semigroups.
AB  - The aim of this paper is to investigate the lattices of group fuzzy congruences
      and normal fuzzy subsemigroups on E-inversive semigroups. We prove that group
      fuzzy congruences and normal fuzzy subsemigroups determined each other in E
      inversive semigroups. Moreover, we show that the set of group t-fuzzy congruences
      and the set of normal subsemigroups with tip t in a given E-inversive semigroup
      form two mutually isomorphic modular lattices for every t ? [0,1].

PMID- 24892044
TI  - Effects of different vegetation zones on CH4 and N2O emissions in coastal
      wetlands: a model case study.
AB  - The coastal wetland ecosystems are important in the global carbon and nitrogen
      cycle and global climate change. For higher fragility of coastal wetlands induced
      by human activities, the roles of coastal wetland ecosystems in CH4 and N2O
      emissions are becoming more important. This study used a DNDC model to simulate
      current and future CH4 and N2O emissions of coastal wetlands in four sites along
      the latitude in China. The simulation results showed that different vegetation
      zones, including bare beach, Spartina beach, and Phragmites beach, produced
      different emissions of CH4 and N2O in the same latitude region. Correlation
      analysis indicated that vegetation types, water level, temperature, and soil
      organic carbon content are the main factors affecting emissions of CH4 and N2O in
      coastal wetlands. 

PMID- 24892046
TI  - An optimization method for condition based maintenance of aircraft fleet
      considering prognostics uncertainty.
AB  - An optimization method for condition based maintenance (CBM) of aircraft fleet
      considering prognostics uncertainty is proposed. The CBM and dispatch process of
      aircraft fleet is analyzed first, and the alternative strategy sets for single
      aircraft are given. Then, the optimization problem of fleet CBM with lower
      maintenance cost and dispatch risk is translated to the combinatorial
      optimization problem of single aircraft strategy. Remain useful life (RUL)
      distribution of the key line replaceable Module (LRM) has been transformed into
      the failure probability of the aircraft and the fleet health status matrix is
      established. And the calculation method of the costs and risks for mission based
      on health status matrix and maintenance matrix is given. Further, an optimization
      method for fleet dispatch and CBM under acceptable risk is proposed based on an
      improved genetic algorithm. Finally, a fleet of 10 aircrafts is studied to verify
      the proposed method. The results shows that it could realize optimization and
      control of the aircraft fleet oriented to mission success. 

PMID- 24892047
TI  - End-completely-regular and end-inverse lexicographic products of graphs.
AB  - A graph X is said to be End-completely-regular (resp., End-inverse) if its
      endomorphism monoid End(X) is completely regular (resp., inverse). In this paper,
      we will show that if X[Y] is End-completely-regular (resp., End-inverse), then
      both X and Y are End-completely-regular (resp., End-inverse). We give several
      approaches to construct new End-completely-regular graphs by means of the
      lexicographic products of two graphs with certain conditions. In particular, we
      determine the End-completely-regular and End-inverse lexicographic products of
      bipartite graphs. 

PMID- 24892048
TI  - Evolutionary multiobjective query workload optimization of Cloud data warehouses.
AB  - With the advent of Cloud databases, query optimizers need to find paretooptimal
      solutions in terms of response time and monetary cost. Our novel approach
      minimizes both objectives by deploying alternative virtual resources and query
      plans making use of the virtual resource elasticity of the Cloud. We propose an
      exact multiobjective branch-and-bound and a robust multiobjective genetic
      algorithm for the optimization of distributed data warehouse query workloads on
      the Cloud. In order to investigate the effectiveness of our approach, we
      incorporate the devised algorithms into a prototype system. Finally, through
      several experiments that we have conducted with different workloads and virtual
      resource configurations, we conclude remarkable findings of alternative
      deployments as well as the advantages and disadvantages of the multiobjective
      algorithms we propose. 

PMID- 24892049
TI  - Modeling, control, and simulation of battery storage photovoltaic-wave energy
      hybrid renewable power generation systems for island electrification in Malaysia.
AB  - Today, the whole world faces a great challenge to overcome the environmental
      problems related to global energy production. Most of the islands throughout the
      world depend on fossil fuel importation with respect to energy production. Recent
      development and research on green energy sources can assure sustainable power
      supply for the islands. But unpredictable nature and high dependency on weather
      conditions are the main limitations of renewable energy sources. To overcome this
      drawback, different renewable sources and converters need to be integrated with
      each other. This paper proposes a standalone hybrid photovoltaic- (PV-) wave
      energy conversion system with energy storage. In the proposed hybrid system,
      control of the bidirectional buck-boost DC-DC converter (BBDC) is used to
      maintain the constant dc-link voltage. It also accumulates the excess hybrid
      power in the battery bank and supplies this power to the system load during the
      shortage of hybrid power. A three-phase complex vector control scheme voltage
      source inverter (VSI) is used to control the load side voltage in terms of the
      frequency and voltage amplitude. Based on the simulation results obtained from
      Matlab/Simulink, it has been found that the overall hybrid framework is capable
      of working under the variable weather and load conditions. 

PMID- 24892051
TI  - Solution of some types of differential equations: operational calculus and
      inverse differential operators.
AB  - We present a general method of operational nature to analyze and obtain solutions
      for a variety of equations of mathematical physics and related mathematical
      problems. We construct inverse differential operators and produce operational
      identities, involving inverse derivatives and families of generalised orthogonal
      polynomials, such as Hermite and Laguerre polynomial families. We develop the
      methodology of inverse and exponential operators, employing them for the study of
      partial differential equations. Advantages of the operational technique, combined
      with the use of integral transforms, generating functions with exponentials and
      their integrals, for solving a wide class of partial derivative equations,
      related to heat, wave, and transport problems, are demonstrated. 

PMID- 24892050
TI  - Double-framed soft hypervector spaces.
AB  - The notions of double-framed soft subfields, double-framed soft algebras over
      double-framed soft subfields, and double-framed soft hypervector spaces are
      introduced, and their properties and characterizations are considered. 

PMID- 24892052
TI  - Novel web service selection model based on discrete group search.
AB  - In our earlier work, we present a novel formal method for the semiautomatic
      verification of specifications and for describing web service composition
      components by using abstract concepts. After verification, the instantiations of
      components were selected to satisfy the complex service performance constraints.
      However, selecting an optimal instantiation, which comprises different candidate
      services for each generic service, from a large number of instantiations is
      difficult. Therefore, we present a new evolutionary approach on the basis of the
      discrete group search service (D-GSS) model. With regard to obtaining the optimal
      multiconstraint instantiation of the complex component, the D-GSS model has
      competitive performance compared with other service selection models in terms of
      accuracy, efficiency, and ability to solve high-dimensional service composition
      component problems. We propose the cost function and the discrete group search
      optimizer (D-GSO) algorithm and study the convergence of the D-GSS model through
      verification and test cases. 

PMID- 24892053
TI  - Compressed sensing based fingerprint identification for wireless transmitters.
AB  - Most of the existing fingerprint identification techniques are unable to
      distinguish different wireless transmitters, whose emitted signals are highly
      attenuated, long-distance propagating, and of strong similarity to their
      transient waveforms. Therefore, this paper proposes a new method to identify
      different wireless transmitters based on compressed sensing. A data acquisition
      system is designed to capture the wireless transmitter signals. Complex
      analytical wavelet transform is used to obtain the envelope of the transient
      signal, and the corresponding features are extracted by using the compressed
      sensing theory. Feature selection utilizing minimum redundancy maximum relevance
      (mRMR) is employed to obtain the optimal feature subsets for identification. The
      results show that the proposed method is more efficient for the identification of
      wireless transmitters with similar transient waveforms. 

PMID- 24892054
TI  - Historical feature pattern extraction based network attack situation sensing
      algorithm.
AB  - The situation sequence contains a series of complicated and multivariate random
      trends, which are very sudden, uncertain, and difficult to recognize and describe
      its principle by traditional algorithms. To solve the above questions, estimating
      parameters of super long situation sequence is essential, but very difficult, so
      this paper proposes a situation prediction method based on historical feature
      pattern extraction (HFPE). First, HFPE algorithm seeks similar indications from
      the history situation sequence recorded and weighs the link intensity between
      occurred indication and subsequent effect. Then it calculates the probability
      that a certain effect reappears according to the current indication and makes a
      prediction after weighting. Meanwhile, HFPE method gives an evolution algorithm
      to derive the prediction deviation from the views of pattern and accuracy. This
      algorithm can continuously promote the adaptability of HFPE through gradual fine
      tuning. The method preserves the rules in sequence at its best, does not need
      data preprocessing, and can track and adapt to the variation of situation
      sequence continuously. 

PMID- 24892056
TI  - Extending an almost complete pair of matrices to a complete triple.
AB  - Motivated by the concept of complete pairs, which was introduced by Krein and
      Langer, we present the concepts of an almost complete pair of matrices and a
      complete triple of matrices. It is proved that an almost complete pair of
      matrices can be extended to a complete triple. An application of the result to
      differential equations is also given. 

PMID- 24892055
TI  - Towards emotion detection in educational scenarios from facial expressions and
      body movements through multimodal approaches.
AB  - We report current findings when considering video recordings of facial
      expressions and body movements to provide affective personalized support in an
      educational context from an enriched multimodal emotion detection approach. In
      particular, we describe an annotation methodology to tag facial expression and
      body movements that conform to changes in the affective states of learners while
      dealing with cognitive tasks in a learning process. The ultimate goal is to
      combine these annotations with additional affective information collected during
      experimental learning sessions from different sources such as qualitative, self
      reported, physiological, and behavioral information. These data altogether are to
      train data mining algorithms that serve to automatically identify changes in the
      learners' affective states when dealing with cognitive tasks which help to
      provide emotional personalized support. 

PMID- 24892057
TI  - Hybrid algorithms for fuzzy reverse supply chain network design.
AB  - In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport
      loss ratio, this paper attempted to establish an optimized decision model for
      production planning and distribution of a multiphase, multiproduct reverse supply
      chain, which addresses defects returned to original manufacturers, and in
      addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic
      Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle
      Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model.
      During a case study of a multi-phase, multi-product reverse supply chain network,
      this paper explained the suitability of the optimized decision model and the
      applicability of the algorithms. Finally, the hybrid algorithms showed excellent
      solving capability when compared with original GA and PSO methods. 

PMID- 24892058
TI  - Multivariate-statistical assessment of heavy metals for agricultural soils in
      northern China.
AB  - The study evaluated eight heavy metals content and soil pollution from
      agricultural soils in northern China. Multivariate and geostatistical analysis
      approaches were used to determine the anthropogenic and natural contribution of
      soil heavy metal concentrations. Single pollution index and integrated pollution
      index could be used to evaluate soil heavy metal risk. The results show that the
      first factor explains 27.3% of the eight soil heavy metals with strong positive
      loadings on Cu, Zn, and Cd, which indicates that Cu, Zn, and Cd are associated
      with and controlled by anthropic activities. The average value of heavy metal is
      lower than the second grade standard values of soil environmental quality
      standards in China. Single pollution index is lower than 1, and the Nemerow
      integrated pollution index is 0.305, which means that study area has not been
      polluted. The semivariograms of soil heavy metal single pollution index fitted
      spherical and exponential models. The variable ratio of single pollution index
      showed moderately spatial dependence. Heavy metal contents showed relative safety
      in the study area. 

PMID- 24892059
TI  - A fast elitism Gaussian estimation of distribution algorithm and application for
      PID optimization.
AB  - Estimation of distribution algorithm (EDA) is an intelligent optimization
      algorithm based on the probability statistics theory. A fast elitism Gaussian
      estimation of distribution algorithm (FEGEDA) is proposed in this paper. The
      Gaussian probability model is used to model the solution distribution. The
      parameters of Gaussian come from the statistical information of the best
      individuals by fast learning rule. A fast learning rule is used to enhance the
      efficiency of the algorithm, and an elitism strategy is used to maintain the
      convergent performance. The performances of the algorithm are examined based upon
      several benchmarks. In the simulations, a one-dimensional benchmark is used to
      visualize the optimization process and probability model learning process during
      the evolution, and several two-dimensional and higher dimensional benchmarks are
      used to testify the performance of FEGEDA. The experimental results indicate the
      capability of FEGEDA, especially in the higher dimensional problems, and the
      FEGEDA exhibits a better performance than some other algorithms and EDAs.
      Finally, FEGEDA is used in PID controller optimization of PMSM and compared with
      the classical-PID and GA. 

PMID- 24892060
TI  - Unsteady boundary-layer flow over jerked plate moving in a free stream of
      viscoelastic fluid.
AB  - This study aims to investigate the unsteady boundary-layer flow of a viscoelastic
      non-Newtonian fluid over a flat surface. The plate is suddenly jerked to move
      with uniform velocity in a uniform stream of non-Newtonian fluid. Purely analytic
      solution to governing nonlinear equation is obtained. The solution is highly
      accurate and valid for all values of the dimensionless time 0 <= tau < infinity.
      Flow properties of the viscoelastic fluid are discussed through graphs. 

PMID- 24892061
TI  - Selecting single model in combination forecasting based on cointegration test and
      encompassing test.
AB  - Combination forecasting takes all characters of each single forecasting method
      into consideration, and combines them to form a composite, which increases
      forecasting accuracy. The existing researches on combination forecasting select
      single model randomly, neglecting the internal characters of the forecasting
      object. After discussing the function of cointegration test and encompassing test
      in the selection of single model, supplemented by empirical analysis, the paper
      gives the single model selection guidance: no more than five suitable single
      models can be selected from many alternative single models for a certain
      forecasting target, which increases accuracy and stability. 

PMID- 24892062
TI  - Adaptive phase rolling for opportunistic beamforming in OFDMA systems with a
      small number of users.
AB  - The performance of opportunistic beamforming might be degraded if the number of
      users is small. This paper proposes an adaptive opportunistic beamforming
      technique for orthogonal frequency division multiple access systems, which can
      produce good results even with a small number of users. This paper also proposes
      a modified proportional fairness scheduling algorithm, which can further improve
      the performance of the proposed opportunistic beamforming technique. 

PMID- 24892063
TI  - Patterns of nonemergent visits to different healthcare facilities on the same
      day: a nationwide analysis in Taiwan.
AB  - Doctor shopping is a common phenomenon in many countries. However, patterns of
      switching healthcare facilities on the same day were little known. The data were
      obtained from the longitudinal cohort datasets (LHID2010) of Taiwan's National
      Health Insurance Research Database in 2010. Of 1,000,000 persons of the cohort
      with 13,276,928 nonemergent visits, 185,347 patients had visited different
      healthcare facilities within one day, with a total of 672,478 visits and 337,260
      switches between facilities in 329,073 patient-days. While 63.0% (n = 212,590) of
      all switches occurred between facilities of the same accreditation level, 14.1%
      (n = 47,664) moved from lower to higher level, and 22.8% (n = 77,006) moved in
      the opposite direction. In 33,689 switches, patients moved to the same specialty
      of another facility. In 48,324 switches, patients moved to another facility with
      the same diagnosis, and the most frequent diagnoses were diseases of the
      digestive system (11,148) and diseases of the respiratory system (10,393). In a
      densely populated country without strict referral regulation, a high percentage
      of Taiwanese people had the experience of visiting different healthcare
      facilities on the same day. The system of family physicians as personal doctors
      and gatekeepers to healthcare might ameliorate the harmful impact. 

PMID- 24892064
TI  - A system for sentiment analysis of colloquial Arabic using human computation.
AB  - We present the implementation and evaluation of a sentiment analysis system that
      is conducted over Arabic text with evaluative content. Our system is broken into
      two different components. The first component is a game that enables users to
      annotate large corpuses of text in a fun manner. The game produces necessary
      linguistic resources that will be used by the second component which is the
      sentimental analyzer. Two different algorithms have been designed to employ these
      linguistic resources to analyze text and classify it according to its sentimental
      polarity. The first approach is using sentimental tag patterns, which reached a
      precision level of 56.14%. The second approach is the sentimental majority
      approach which relies on calculating the number of negative and positive phrases
      in the sentence and classifying the sentence according to the dominant polarity.
      The results after evaluating the system for the first sentimental majority
      approach yielded the highest accuracy level reached by our system which is 60.5%
      while the second variation scored an accuracy of 60.32%. 

PMID- 24892065
TI  - Absolute stability criteria for large-scale Lurie direct control systems with
      time-varying coefficients.
AB  - The absolute stability of large-scale Lurie direct control systems with time
      varying coefficients is investigated. Based on the decomposition method for large
      scale systems and technique of the nonsingular M-matrix, a suitable scalar
      Lyapunov function as a weighted sum is constructed. By estimating its total time
      derivative, some absolute stability criteria and practical corollaries are
      derived. Furthermore, the results are extended to multiple nonlinearities. The
      salient feature of this paper is that the criteria which we propose allow for the
      situation that the norms of time-varying coefficients are unbounded. The main
      idea of the methodology is that even if the coefficients are norm-unbounded, by
      restricting their relative magnitude, the problem of negative definiteness for
      the derivative can also be changed into the problem of stability for a constant
      matrix. Finally, some numerical examples are included to illustrate the
      effectiveness of the proposed criteria. 

PMID- 24892066
TI  - Monitoring the invasion of Spartina alterniflora using very high resolution
      unmanned aerial vehicle imagery in Beihai, Guangxi (China).
AB  - Spartina alterniflora was introduced to Beihai, Guangxi (China), for ecological
      engineering purposes in 1979. However, the exceptional adaptability and
      reproductive ability of this species have led to its extensive dispersal into
      other habitats, where it has had a negative impact on native species and
      threatens the local mangrove and mudflat ecosystems. To obtain the distribution
      and spread of Spartina alterniflora, we collected HJ-1 CCD imagery from 2009 and
      2011 and very high resolution (VHR) imagery from the unmanned aerial vehicle
      (UAV). The invasion area of Spartina alterniflora was 357.2 ha in 2011, which
      increased by 19.07% compared with the area in 2009. A field survey was conducted
      for verification and the total accuracy was 94.0%. The results of this paper show
      that VHR imagery can provide details on distribution, progress, and early
      detection of Spartina alterniflora invasion. OBIA, object based image analysis
      for remote sensing (RS) detection method, can enable control measures to be more
      effective, accurate, and less expensive than a field survey of the invasive
      population.

PMID- 24892067
TI  - Commutators of singular integral operators satisfying a variant of a Lipschitz
      condition.
AB  - Let T be a singular integral operator with its kernel satisfying |K(x - y) -
      ?(k=1)(l) ?Bk (x)phik(y)| <= C| y| (gamma)/|x - y| (n+gamma), |x | > 2| y| > 0,
      where B(k) and phik (k = 1,..., l) are appropriate functions and gamma and C are
      positive constants. For b = b1'...,bm) with bj ? BMO(R(n)), the multilinear
      commutator Tb generated by T and b is formally defined by T(b)f(x) =
      ?(Rn)[?(j=1)(m) (b(j)(x) - b(j)(y))] K(x, y)f(y)dy. In this paper, the weighted
      L(p)-boundedness and the weighted weak type L log estimate for the multilinear
      commutator T(b) are established.

PMID- 24892068
TI  - A color gamut description algorithm for liquid crystal displays in CIELAB space.
AB  - Because the accuracy of gamut boundary description is significant for gamut
      mapping process, a gamut boundary calculating method for LCD monitors is proposed
      in this paper. Within most of the previous gamut boundary calculation algorithms,
      the gamut boundary is calculated in CIELAB space directly, and part of inside
      gamut points are mistaken for the boundary points. While, in the new proposed
      algorithm, the points on the surface of RGB cube are selected as the boundary
      points, and then converted and described in CIELAB color space. Thus, in our
      algorithm, the true gamut boundary points are found and a more accurate gamut
      boundary is described. In experiment, a Toshiba LCD monitor's 3D CIELAB gamut for
      evaluation is firstly described which has regular-shaped outer surface, and then
      two 2D gamut boundaries ( CIE-a*b* boundary and CIE-C*L* boundary) are calculated
      which are often used in gamut mapping process. When our algorithm is compared
      with several famous gamut calculating algorithms, the gamut volumes are very
      close, which indicates that our algorithm's accuracy is precise and acceptable. 

PMID- 24892069
TI  - Monte Carlo method with heuristic adjustment for irregularly shaped food product
      volume measurement.
AB  - Volume measurement plays an important role in the production and processing of
      food products. Various methods have been proposed to measure the volume of food
      products with irregular shapes based on 3D reconstruction. However, 3D
      reconstruction comes with a high-priced computational cost. Furthermore, some of
      the volume measurement methods based on 3D reconstruction have a low accuracy.
      Another method for measuring volume of objects uses Monte Carlo method. Monte
      Carlo method performs volume measurements using random points. Monte Carlo method
      only requires information regarding whether random points fall inside or outside
      an object and does not require a 3D reconstruction. This paper proposes volume
      measurement using a computer vision system for irregularly shaped food products
      without 3D reconstruction based on Monte Carlo method with heuristic adjustment.
      Five images of food product were captured using five cameras and processed to
      produce binary images. Monte Carlo integration with heuristic adjustment was
      performed to measure the volume based on the information extracted from binary
      images. The experimental results show that the proposed method provided high
      accuracy and precision compared to the water displacement method. In addition,
      the proposed method is more accurate and faster than the space carving method. 

PMID- 24892070
TI  - Cloud computing based systems for healthcare.

PMID- 24892071
TI  - Type-II fuzzy decision support system for fertilizer.
AB  - Type-II fuzzy sets are used to convey the uncertainties in the membership
      function of type-I fuzzy sets. Linguistic information in expert rules does not
      give any information about the geometry of the membership functions. These
      membership functions are mostly constructed through numerical data or range of
      classes. But there exists an uncertainty about the shape of the membership, that
      is, whether to go for a triangle membership function or a trapezoidal membership
      function. In this paper we use a type-II fuzzy set to overcome this uncertainty,
      and develop a fuzzy decision support system of fertilizers based on a type-II
      fuzzy set. This type-II fuzzy system takes cropping time and soil nutrients in
      the form of spatial surfaces as input, fuzzifies it using a type-II fuzzy
      membership function, and implies fuzzy rules on it in the fuzzy inference engine.
      The output of the fuzzy inference engine, which is in the form of interval value
      type-II fuzzy sets, reduced to an interval type-I fuzzy set, defuzzifies it to a
      crisp value and generates a spatial surface of fertilizers. This spatial surface
      shows the spatial trend of the required amount of fertilizer needed to cultivate
      a specific crop. The complexity of our algorithm is O(mnr), where m is the height
      of the raster, n is the width of the raster, and r is the number of expert rules.

PMID- 24892072
TI  - On lightlike geometry of para-Sasakian manifolds.
AB  - We study lightlike hypersurfaces of para-Sasakian manifolds tangent to the
      characteristic vector field. In particular, we define invariant lightlike
      hypersurfaces and screen semi-invariant lightlike hypersurfaces, respectively,
      and give examples. Integrability conditions for the distributions on a screen
      semi-invariant lightlike hypersurface of para-Sasakian manifolds are
      investigated. We obtain a para-Sasakian structure on the leaves of an integrable
      distribution of a screen semi-invariant lightlike hypersurface. 

PMID- 24892073
TI  - Research on grading detection of the wheat seeds.
AB  - Evaluating the merits of the wheat seed is an important significance for wheat
      breeding. We studied analytic hierarchy process (AHP) for seeds grading by
      digital image processing techniques in the paper. Firstly, preprocess the
      collected wheat seed images; extract some parameters, such as area, plumpness,
      rectangular, and elongation of the seed, and then build the level model.
      Experiments showed the model is right, and level accuracy rate is more than 95%. 

PMID- 24892074
TI  - Algorithm for image retrieval based on edge gradient orientation statistical
      code.
AB  - Image edge gradient direction not only contains important information of the
      shape, but also has a simple, lower complexity characteristic. Considering that
      the edge gradient direction histograms and edge direction autocorrelogram do not
      have the rotation invariance, we put forward the image retrieval algorithm which
      is based on edge gradient orientation statistical code (hereinafter referred to
      as EGOSC) by sharing the application of the statistics method in the edge
      direction of the chain code in eight neighborhoods to the statistics of the edge
      gradient direction. Firstly, we construct the n-direction vector and make maximal
      summation restriction on EGOSC to make sure this algorithm is invariable for
      rotation effectively. Then, we use Euclidean distance of edge gradient direction
      entropy to measure shape similarity, so that this method is not sensitive to
      scaling, color, and illumination change. The experimental results and the
      algorithm analysis demonstrate that the algorithm can be used for content-based
      image retrieval and has good retrieval results. 

PMID- 24892075
TI  - Decision support model for introduction of gamification solution using AHP.
AB  - Gamification means the use of various elements of game design in nongame contexts
      including workplace collaboration, marketing, education, military, and medical
      services. Gamification is effective for both improving workplace productivity and
      motivating employees. However, introduction of gamification is not easy because
      the planning and implementation processes of gamification are very complicated
      and it needs interdisciplinary knowledge such as information systems,
      organization behavior, and human psychology. Providing a systematic decision
      making method for gamification process is the purpose of this paper. This paper
      suggests the decision criteria for selection of gamification platform to support
      a systematic decision making process for managements. The criteria are derived
      from previous works on gamification, introduction of information systems, and
      analytic hierarchy process. The weights of decision criteria are calculated
      through a survey by the professionals on game, information systems, and business
      administration. The analytic hierarchy process is used to derive the weights. The
      decision criteria and weights provided in this paper could support the
      managements to make a systematic decision for selection of gamification platform.

PMID- 24892076
TI  - Bifurcations of nontwisted heteroclinic loop with resonant eigenvalues.
AB  - By using the foundational solutions of the linear variational equation of the
      unperturbed system along the heteroclinic orbits to establish the local
      coordinate systems in the small tubular neighborhoods of the heteroclinic orbits,
      we study the bifurcation problems of nontwisted heteroclinic loop with resonant
      eigenvalues. The existence, numbers, and existence regions of 1-heteroclinic
      loop, 1-homoclinic loop, 1-periodic orbit, 2-fold 1-periodic orbit, and two 1
      periodic orbits are obtained. Meanwhile, we give the corresponding bifurcation
      surfaces. 

PMID- 24892077
TI  - Gaining surgical access for repositioning the inferior alveolar neurovascular
      bundle.
AB  - This study is aimed at determining anatomical landmarks that can be used to gain
      access to the inferior alveolar neurovascular (IAN) bundle. Scanned CBCT (i-CAT
      machine) data of sixty patients and reconstructions performed using the SimPlant
      dental implant software were reviewed. Outcome variables were the linear
      distances of the mandibular canal to the inferior border and the buccal cortex of
      the mandible, measured immediately at the mental foramen (D1) and at 10, 20, 30,
      and 40 mm (D2-D5) distal to it. Predictor variables were age, ethnicity, and
      gender of subjects. Apicobasal assessment of the canal reveals that it is curving
      downward towards the inferior mandibular border until 20 mm (D3) distal to the
      mental foramen where it then curves upwards, making an elliptic-arc curve. The
      mandibular canal also forms a buccolingually oriented elliptic arc in relation to
      the buccal cortex. Variations due to age, ethnicity, and gender were evident and
      this study provides an accurate anatomic zone for gaining surgical access to the
      IAN bundle. The findings indicate that the buccal cortex-IAN distance was
      greatest at D3. Therefore, sites between D2 and D5 can be used as favorable
      landmarks to access the IAN bundle with the least complications to the patient.

PMID- 24892078
TI  - A robust and effective smart-card-based remote user authentication mechanism
      using hash function.
AB  - In a remote user authentication scheme, a remote server verifies whether a login
      user is genuine and trustworthy, and also for mutual authentication purpose a
      login user validates whether the remote server is genuine and trustworthy.
      Several remote user authentication schemes using the password, the biometrics,
      and the smart card have been proposed in the literature. However, most schemes
      proposed in the literature are either computationally expensive or insecure
      against several known attacks. In this paper, we aim to propose a new robust and
      effective password-based remote user authentication scheme using smart card. Our
      scheme is efficient, because our scheme uses only efficient one-way hash function
      and bitwise XOR operations. Through the rigorous informal and formal security
      analysis, we show that our scheme is secure against possible known attacks. We
      perform the simulation for the formal security analysis using the widely accepted
      AVISPA (Automated Validation Internet Security Protocols and Applications) tool
      to ensure that our scheme is secure against passive and active attacks.
      Furthermore, our scheme supports efficiently the password change phase always
      locally without contacting the remote server and correctly. In addition, our
      scheme performs significantly better than other existing schemes in terms of
      communication, computational overheads, security, and features provided by our
      scheme. 

PMID- 24892080
TI  - Real-time extended interface automata for software testing cases generation.
AB  - Testing and verification of the interface between software components are
      particularly important due to the large number of complex interactions, which
      requires the traditional modeling languages to overcome the existing shortcomings
      in the aspects of temporal information description and software testing input
      controlling. This paper presents the real-time extended interface automata
      (RTEIA) which adds clearer and more detailed temporal information description by
      the application of time words. We also establish the input interface automaton
      for every input in order to solve the problems of input controlling and interface
      covering nimbly when applied in the software testing field. Detailed definitions
      of the RTEIA and the testing cases generation algorithm are provided in this
      paper. The feasibility and efficiency of this method have been verified in the
      testing of one real aircraft braking system. 

PMID- 24892079
TI  - The influence of the social support on symptoms of anxiety and depression among
      patients with silicosis.
AB  - The improvement of social support promotes the mental health and improves the
      health status. The study aimed to examine the influence of the social support on
      symptoms of anxiety and depression among patients with silicosis and provide the
      scientific basis to further alleviate anxiety and depression and to monitor their
      whole quality of life. We investigated 324 inpatients with silicosis between
      April 2011 and September 2011. The HADS (the Hospital Anxiety-Depression Scale)
      was the major methodology used to evaluate anxiety and depression, and the MSPSS
      (the Multidimensional Scale of Perceived Social Support) to evaluate the social
      support level. Among patients with silicosis, 99.1% had anxiety symptoms, and
      86.1% had depression symptoms. Meanwhile, the social support significantly
      influenced symptoms of anxiety and depression. The study suggested that patients
      with silicosis presented more anxiety and depression symptoms, while the social
      support levels of the patients were relatively low. The influence of social
      support on symptoms of anxiety and depression among patients with silicosis
      implied that improving the level of social support and the effective symptomatic
      treatment might alleviate anxiety and depression symptoms and improve physical
      and mental status. 

PMID- 24892081
TI  - Gender classification based on geometry features of palm image.
AB  - This paper presents a novel gender classification method based on geometry
      features of palm image which is simple, fast, and easy to handle. This gender
      classification method based on geometry features comprises two main attributes.
      The first one is feature extraction by image processing. The other one is
      classification system with polynomial smooth support vector machine (PSSVM). A
      total of 180 palm images were collected from 30 persons to verify the validity of
      the proposed gender classification approach and the results are satisfactory with
      classification rate over 85%. Experimental results demonstrate that our proposed
      approach is feasible and effective in gender recognition. 

PMID- 24892082
TI  - Critical care and perioperative monitoring.

PMID- 24892083
TI  - Study of silver nanoparticles sensitized fluorescence and second-order scattering
      of terbium(III)-pefloxacin mesylate complex and determination of pefloxacin
      mesylate.
AB  - alpha-Keto acid of pefloxacin mesylate (PFLX) can form the complex with
      Terbium(III). The intramolecular energy from PFLX to Terbium(III) ion takes place
      when excited, and thus Terbium(III) excited state is formed and then emits the
      characteristic fluorescence of Terbium(III), locating at 490, 545, 580, and 620
      nm. The second-order scattering (SOS) peak at 545 nm also appears for the complex
      with the exciting wavelength of 273 nm. When the silver nanoparticles are added
      to the system, the luminescence intensity at 545 nm greatly increased. So, with
      the adding of nanoparticles to the Terbium(III)-PFLX complex, not only is the
      intramolecular energy promoted but also the SOS intensity is enhanced. The
      experimental results show that it is the silver nanoparticles with certain size
      and certain concentration which can greatly enhance the fluorescence-SOS
      intensity, and the relative intensity at 545 nm is proportional to the amount of
      PFLX. Based on this phenomenon, a novel method for the determination of PFLX has
      been developed and applied to the determination of PFLX in capsule and serum
      samples.

PMID- 24892085
TI  - On fuzzy ideals of BL-algebras.
AB  - In this paper we investigate further properties of fuzzy ideals of a BL-algebra.
      The notions of fuzzy prime ideals, fuzzy irreducible ideals, and fuzzy Godel
      ideals of a BL-algebra are introduced and their several properties are
      investigated. We give a procedure to generate a fuzzy ideal by a fuzzy set. We
      prove that every fuzzy irreducible ideal is a fuzzy prime ideal but a fuzzy prime
      ideal may not be a fuzzy irreducible ideal and prove that a fuzzy prime ideal
      omega is a fuzzy irreducible ideal if and only if omega(0) = 1 and |Im(omega)| =
      2. We give the Krull-Stone representation theorem of fuzzy ideals in BL-algebras.
      Furthermore, we prove that the lattice of all fuzzy ideals of a BL-algebra is a
      complete distributive lattice. Finally, it is proved that every fuzzy Boolean
      ideal is a fuzzy Godel ideal, but the converse implication is not true.

PMID- 24892084
TI  - Characterization of affinity-purified isoforms of Acinetobacter calcoaceticus Y1
      glutathione transferases.
AB  - Glutathione transferases (GST) were purified from locally isolated bacteria,
      Acinetobacter calcoaceticus Y1, by glutathione-affinity chromatography and anion
      exchange, and their substrate specificities were investigated. SDS-polyacrylamide
      gel electrophoresis revealed that the purified GST resolved into a single band
      with a molecular weight (MW) of 23 kDa. 2-dimensional (2-D) gel electrophoresis
      showed the presence of two isoforms, GST1 (pI 4.5) and GST2 (pI 6.2) with
      identical MW. GST1 was reactive towards ethacrynic acid, hydrogen peroxide, 1
      chloro-2,4-dinitrobenzene, and trans,trans-hepta-2,4-dienal while GST2 was active
      towards all substrates except hydrogen peroxide. This demonstrated that GST1
      possessed peroxidase activity which was absent in GST2. This study also showed
      that only GST2 was able to conjugate GSH to isoproturon, a herbicide. GST1 and
      GST2 were suggested to be similar to F0KLY9 (putative glutathione S-transferase)
      and F0KKB0 (glutathione S-transferase III) of Acinetobacter calcoaceticus strain
      PHEA-2, respectively.

PMID- 24892086
TI  - Unsupervised quality estimation model for English to German translation and its
      application in extensive supervised evaluation.
AB  - With the rapid development of machine translation (MT), the MT evaluation becomes
      very important to timely tell us whether the MT system makes any progress. The
      conventional MT evaluation methods tend to calculate the similarity between
      hypothesis translations offered by automatic translation systems and reference
      translations offered by professional translators. There are several weaknesses in
      existing evaluation metrics. Firstly, the designed incomprehensive factors result
      in language-bias problem, which means they perform well on some special language
      pairs but weak on other language pairs. Secondly, they tend to use no linguistic
      features or too many linguistic features, of which no usage of linguistic feature
      draws a lot of criticism from the linguists and too many linguistic features make
      the model weak in repeatability. Thirdly, the employed reference translations are
      very expensive and sometimes not available in the practice. In this paper, the
      authors propose an unsupervised MT evaluation metric using universal part-of
      speech tagset without relying on reference translations. The authors also explore
      the performances of the designed metric on traditional supervised evaluation
      tasks. Both the supervised and unsupervised experiments show that the designed
      methods yield higher correlation scores with human judgments. 

PMID- 24892087
TI  - Analysis of fractional dynamic systems.

PMID- 24892088
TI  - H infinity cluster synchronization for a class of neutral complex dynamical
      networks with Markovian switching.
AB  - H infinity cluster synchronization problem for a class of neutral complex
      dynamical networks (NCDNs) with Markovian switching is investigated in this
      paper. Both the retarded and neutral delays are considered to be interval mode
      dependent and time varying. The concept of H infinity cluster synchronization is
      proposed to quantify the attenuation level of synchronization error dynamics
      against the exogenous disturbance of the NCDNs. Based on a novel Lyapunov
      functional, by employing some integral inequalities and the nature of convex
      combination, mode delay-range-dependent H infinity cluster synchronization
      criteria are derived in the form of linear matrix inequalities which depend not
      only on the disturbance attenuation but also on the initial values of the NCDNs.
      Finally, numerical examples are given to demonstrate the feasibility and
      effectiveness of the proposed theoretical results. 

PMID- 24892090
TI  - Improved stabilization method for Lurie networked control systems.
AB  - The problem of stabilization of Lurie networked control systems (NCSs) is
      investigated in this paper. The network-induced delays in NCSs are assumed to be
      time-varying and bounded. By utilizing a reciprocally convex technique to
      consider the relationship between the network-induced delay and its varying
      interval, a new absolute stability condition is derived in terms of linear matrix
      inequalities (LMIs). Based on the obtained condition, an improved cone
      complementary linearisation (CCL) iteration algorithm is presented to design a
      state feedback controller. The effectiveness of the proposed method is verified
      by a numerical example. 

PMID- 24892089
TI  - A method for calculating the area of Zostera marina leaves from digital images
      with noise induced by humidity content.
AB  - Despite the ecological importance of eelgrass, nowadays anthropogenic influences
      have produced deleterious effects in many meadows worldwide. Transplantation
      plots are commonly used as a feasible remediation scheme. The characterization of
      eelgrass biomass and its dynamics is an important input for the assessment of the
      overall status of both natural and transplanted populations. Particularly, in
      restoration plots it is desirable to obtain nondestructive assessments of these
      variables. Allometric models allow the expression of above ground biomass and
      productivity of eelgrass in terms of leaf area, which provides cost effective and
      nondestructive assessments. Leaf area in eelgrass can be conveniently obtained by
      the product of associated length and width. Although these variables can be
      directly measured on most sampled leaves, digital image methods could be adapted
      in order to simplify measurements. Nonetheless, since width to length ratios in
      eelgrass leaves could be even negligible, noise induced by leaf humidity content
      could produce misidentification of pixels along the peripheral contour of leaves
      images. In this paper, we present a procedure aimed to produce consistent
      estimations of eelgrass leaf area in the presence of the aforementioned noise
      effects. Our results show that digital image procedures can provide reliable,
      nondestructive estimations of eelgrass leaf area. 

PMID- 24892091
TI  - Trajectory-based morphological operators: a model for efficient image processing.
AB  - Mathematical morphology has been an area of intensive research over the last few
      years. Although many remarkable advances have been achieved throughout these
      years, there is still a great interest in accelerating morphological operations
      in order for them to be implemented in real-time systems. In this work, we
      present a new model for computing mathematical morphology operations, the so
      called morphological trajectory model (MTM), in which a morphological filter will
      be divided into a sequence of basic operations. Then, a trajectory-based
      morphological operation (such as dilation, and erosion) is defined as the set of
      points resulting from the ordered application of the instant basic operations.
      The MTM approach allows working with different structuring elements, such as
      disks, and from the experiments, it can be extracted that our method is
      independent of the structuring element size and can be easily applied to
      industrial systems and high-resolution images. 

PMID- 24892092
TI  - A ROM-less direct digital frequency synthesizer based on hybrid polynomial
      approximation.
AB  - In this paper, a novel design approach for a phase to sinusoid amplitude
      converter (PSAC) has been investigated. Two segments have been used to
      approximate the first sine quadrant. A first linear segment is used to fit the
      region near the zero point, while a second fourth-order parabolic segment is used
      to approximate the rest of the sine curve. The phase sample, where the polynomial
      changed, was chosen in such a way as to achieve the maximum spurious free dynamic
      range (SFDR). The invented direct digital frequency synthesizer (DDFS) has been
      encoded in VHDL and post simulation was carried out. The synthesized architecture
      exhibits a promising result of 90 dBc SFDR. The targeted structure is expected to
      show advantages for perceptible reduction of hardware resources and power
      consumption as well as high clock speeds. 

PMID- 24892093
TI  - Log-less metadata management on metadata server for parallel file systems.
AB  - This paper presents a novel metadata management mechanism on the metadata server
      (MDS) for parallel and distributed file systems. In this technique, the client
      file system backs up the sent metadata requests, which have been handled by the
      metadata server, so that the MDS does not need to log metadata changes to
      nonvolatile storage for achieving highly available metadata service, as well as
      better performance improvement in metadata processing. As the client file system
      backs up certain sent metadata requests in its memory, the overhead for handling
      these backup requests is much smaller than that brought by the metadata server,
      while it adopts logging or journaling to yield highly available metadata service.
      The experimental results show that this newly proposed mechanism can
      significantly improve the speed of metadata processing and render a better I/O
      data throughput, in contrast to conventional metadata management schemes, that
      is, logging or journaling on MDS. Besides, a complete metadata recovery can be
      achieved by replaying the backup logs cached by all involved clients, when the
      metadata server has crashed or gone into nonoperational state exceptionally. 

PMID- 24892094
TI  - Palmprint based multidimensional fuzzy vault scheme.
AB  - Fuzzy vault scheme (FVS) is one of the most popular biometric cryptosystems for
      biometric template protection. However, error correcting code (ECC) proposed in
      FVS is not appropriate to deal with real-valued biometric intraclass variances.
      In this paper, we propose a multidimensional fuzzy vault scheme (MDFVS) in which
      a general subspace error-tolerant mechanism is designed and embedded into FVS to
      handle intraclass variances. Palmprint is one of the most important biometrics;
      to protect palmprint templates; a palmprint based MDFVS implementation is also
      presented. Experimental results show that the proposed scheme not only can deal
      with intraclass variances effectively but also could maintain the accuracy and
      meanwhile enhance security. 

PMID- 24892095
TI  - Analyzing the impact of storage shortage on data availability in decentralized
      online social networks.
AB  - Maintaining data availability is one of the biggest challenges in decentralized
      online social networks (DOSNs). The existing work often assumes that the friends
      of a user can always contribute to the sufficient storage capacity to store all
      data. However, this assumption is not always true in today's online social
      networks (OSNs) due to the fact that nowadays the users often use the smart
      mobile devices to access the OSNs. The limitation of the storage capacity in
      mobile devices may jeopardize the data availability. Therefore, it is desired to
      know the relation between the storage capacity contributed by the OSN users and
      the level of data availability that the OSNs can achieve. This paper addresses
      this issue. In this paper, the data availability model over storage capacity is
      established. Further, a novel method is proposed to predict the data availability
      on the fly. Extensive simulation experiments have been conducted to evaluate the
      effectiveness of the data availability model and the on-the-fly prediction. 

PMID- 24892096
TI  - Characterizations of some fuzzy prefilters (filters) in EQ-algebras.
AB  - We introduce and study some types of fuzzy prefilters (filters) in EQ-algebras.
      First, we present several characterizations of fuzzy positive implicative
      prefilters (filters), fuzzy implicative prefilters (filters), and fuzzy fantastic
      prefilters (filters). Next, using their characterizations, we mainly consider the
      relationships among these special fuzzy filters. Particularly, we find some
      conditions under which a fuzzy implicative prefilter (filter) is equivalent to a
      fuzzy positive implicative prefilter (filter). As applications, we obtain some
      new results about classical filters in EQ-algebras and some related results about
      fuzzy filters in residuated lattices. 

PMID- 24892097
TI  - Spatial analysis on future housing markets: economic development and housing
      implications.
AB  - A coupled projection method combining formal modelling and other statistical
      techniques was developed to delineate the relationship between economic and
      social drivers for net new housing allocations. Using the example of employment
      growth in Tyne and Wear, UK, until 2016, the empirical analysis yields housing
      projections at the macro- and microspatial levels (e.g., region to subregion to
      elected ward levels). The results have important implications for the strategic
      planning of locations for housing and employment, demonstrating both intuitively
      and quantitatively how local economic developments affect housing demand. 

PMID- 24892098
TI  - Frequent statement and dereference elimination for imperative and object-oriented
      distributed programs.
AB  - This paper introduces new approaches for the analysis of frequent statement and
      dereference elimination for imperative and object-oriented distributed programs
      running on parallel machines equipped with hierarchical memories. The paper uses
      languages whose address spaces are globally partitioned. Distributed programs
      allow defining data layout and threads writing to and reading from other thread
      memories. Three type systems (for imperative distributed programs) are the tools
      of the proposed techniques. The first type system defines for every program point
      a set of calculated (ready) statements and memory accesses. The second type
      system uses an enriched version of types of the first type system and determines
      which of the ready statements and memory accesses are used later in the program.
      The third type system uses the information gather so far to eliminate unnecessary
      statement computations and memory accesses (the analysis of frequent statement
      and dereference elimination). Extensions to these type systems are also presented
      to cover object-oriented distributed programs. Two advantages of our work over
      related work are the following. The hierarchical style of concurrent parallel
      computers is similar to the memory model used in this paper. In our approach,
      each analysis result is assigned a type derivation (serves as a correctness
      proof). 

PMID- 24892100
TI  - The Owen value of stochastic cooperative game.
AB  - We consider stochastic cooperative game and give it the definition of the Owen
      value, which is obtained by extending the classical case. Then we provide
      explicit expression for the Owen value of the stochastic cooperative game and
      discuss its existence and uniqueness. 

PMID- 24892099
TI  - The dynamic mutation characteristics of thermonuclear reaction in Tokamak.
AB  - The stability and bifurcations of multiple limit cycles for the physical model of
      thermonuclear reaction in Tokamak are investigated in this paper. The one
      dimensional Ginzburg-Landau type perturbed diffusion equations for the density of
      the plasma and the radial electric field near the plasma edge in Tokamak are
      established. First, the equations are transformed to the average equations with
      the method of multiple scales and the average equations turn to be a Z 2
      symmetric perturbed polynomial Hamiltonian system of degree 5. Then, with the
      bifurcations theory and method of detection function, the qualitative behavior of
      the unperturbed system and the number of the limit cycles of the perturbed system
      for certain groups of parameter are analyzed. At last, the stability of the limit
      cycles is studied and the physical meaning of Tokamak equations under these
      parameter groups is given. 

PMID- 24892101
TI  - Cloud based metalearning system for predictive modeling of biomedical data.
AB  - Rapid growth and storage of biomedical data enabled many opportunities for
      predictive modeling and improvement of healthcare processes. On the other side
      analysis of such large amounts of data is a difficult and computationally
      intensive task for most existing data mining algorithms. This problem is
      addressed by proposing a cloud based system that integrates metalearning
      framework for ranking and selection of best predictive algorithms for data at
      hand and open source big data technologies for analysis of biomedical data. 

PMID- 24892102
TI  - Mechanism and design analysis of articulated ankle foot orthoses for drop-foot.
AB  - Robotic technologies are being employed increasingly in the treatment of lower
      limb disabilities. Individuals suffering from stroke and other neurological
      disorders often experience inadequate dorsiflexion during swing phase of the gait
      cycle due to dorsiflexor muscle weakness. This type of pathological gait, mostly
      known as drop-foot gait, has two major complications, foot-slap during loading
      response and toe-drag during swing. Ankle foot orthotic (AFO) devices are mostly
      prescribed to resolve these complications. Existing AFOs are designed with or
      without articulated joint with various motion control elements like springs,
      dampers, four-bar mechanism, series elastic actuator, and so forth. This paper
      examines various AFO designs for drop-foot, discusses the mechanism, and
      identifies limitations and remaining design challenges. Along with two
      commercially available AFOs some designs possess promising prospective to be used
      as daily-wear device. However, the design and mechanism of AFO must ensure
      compactness, light weight, low noise, and high efficiency. These entailments
      present significant engineering challenges to develop a new design with wide
      consumer adoption. 

PMID- 24892103
TI  - Moving object detection using dynamic motion modelling from UAV aerial images.
AB  - Motion analysis based moving object detection from UAV aerial image is still an
      unsolved issue due to inconsideration of proper motion estimation. Existing
      moving object detection approaches from UAV aerial images did not deal with
      motion based pixel intensity measurement to detect moving object robustly.
      Besides current research on moving object detection from UAV aerial images mostly
      depends on either frame difference or segmentation approach separately. There are
      two main purposes for this research: firstly to develop a new motion model called
      DMM (dynamic motion model) and secondly to apply the proposed segmentation
      approach SUED (segmentation using edge based dilation) using frame difference
      embedded together with DMM model. The proposed DMM model provides effective
      search windows based on the highest pixel intensity to segment only specific area
      for moving object rather than searching the whole area of the frame using SUED.
      At each stage of the proposed scheme, experimental fusion of the DMM and SUED
      produces extracted moving objects faithfully. Experimental result reveals that
      the proposed DMM and SUED have successfully demonstrated the validity of the
      proposed methodology. 

PMID- 24892104
TI  - A collaborative scheduling model for the supply-hub with multiple suppliers and
      multiple manufacturers.
AB  - This paper investigates a collaborative scheduling model in the assembly system,
      wherein multiple suppliers have to deliver their components to the multiple
      manufacturers under the operation of Supply-Hub. We first develop two different
      scenarios to examine the impact of Supply-Hub. One is that suppliers and
      manufacturers make their decisions separately, and the other is that the Supply
      Hub makes joint decisions with collaborative scheduling. The results show that
      our scheduling model with the Supply-Hub is a NP-complete problem, therefore, we
      propose an auto-adapted differential evolution algorithm to solve this problem.
      Moreover, we illustrate that the performance of collaborative scheduling by the
      Supply-Hub is superior to separate decision made by each manufacturer and
      supplier. Furthermore, we also show that the algorithm proposed has good
      convergence and reliability, which can be applicable to more complicated supply
      chain environment. 

PMID- 24892105
TI  - Effect of the application of 1-methylcyclopropene and wax emulsions on proximate
      analysis and some antioxidants of soursop (Annona muricata L.).
AB  - The effect of the application of 1-methylcyclopropene (1-MCP) and wax emulsions,
      alone or combined, on composition analysis, vitamin C, polyphenols, and
      antioxidant capacity of soursop was evaluated. Fruits were stored as follows: at
      25  degrees C (control), and at 16  degrees C: fruits sprayed with candelilla or
      flava emulsions, fruits treated with 1500 nL/L of 1-MCP (20  degrees C, 12 h),
      and fruits treated with 1-MCP and then sprayed with emulsions. Fruits were
      allowed to ripen and the edible part was used for analysis. Only fruits stored at
      16  degrees C without 1-MCP showed visible symptoms of chilling injury. Fruits
      treated with 1-MCP combined with flava emulsion maintained in greater extent
      their vitamin C content, dietary fiber, total phenolics content, and antioxidant
      activity. The combination of 1-MCP and emulsions can be utilized in postharvest
      handling of soursop because this combination can preserve its nutritional
      composition and antioxidant activity.

PMID- 24892106
TI  - Hydrochemistry of the hot springs in western Sichuan province related to the
      Wenchuan MS 8.0 earthquake.
AB  - Hydrogeochemistry of 32 hot springs in the western Sichuan Province after the
      Wenchuan MS 8.0 earthquake was investigated by analyzing the concentrations of
      cation and anion and the isotopic compositions of hydrogen and oxygen. The water
      samples of the hot springs were collected four times from June 2008 to April
      2010. Hydrogeochemical data indicated the water samples can be classified into 9
      chemical types. Values of delta D and delta(18)O indicated that the spring waters
      were mainly derived from meteoric precipitation and affected by water-rock
      interaction and mixture of deep fluids. Concentrations of K(+)and SO4(-) of the
      samples from the Kangding district exhibited evident increases before the
      Wenchuan earthquake, indicating more supplement of deep fluids under the increase
      of tectonic stress. The chemical and isotopic variations of the water samples
      from the area closer to the epicenter area can be attributed to variation of
      regional stress field when the aftershock activities became weak.

PMID- 24892107
TI  - A novel artificial bee colony algorithm based on internal-feedback strategy for
      image template matching.
AB  - Image template matching refers to the technique of locating a given reference
      image over a source image such that they are the most similar. It is a
      fundamental mission in the field of visual target recognition. In general, there
      are two critical aspects of a template matching scheme. One is similarity
      measurement and the other is best-match location search. In this work, we choose
      the well-known normalized cross correlation model as a similarity criterion. The
      searching procedure for the best-match location is carried out through an
      internal-feedback artificial bee colony (IF-ABC) algorithm. IF-ABC algorithm is
      highlighted by its effort to fight against premature convergence. This purpose is
      achieved through discarding the conventional roulette selection procedure in the
      ABC algorithm so as to provide each employed bee an equal chance to be followed
      by the onlooker bees in the local search phase. Besides that, we also suggest
      efficiently utilizing the internal convergence states as feedback guidance for
      searching intensity in the subsequent cycles of iteration. We have investigated
      four ideal template matching cases as well as four actual cases using different
      searching algorithms. Our simulation results show that the IF-ABC algorithm is
      more effective and robust for this template matching mission than the
      conventional ABC and two state-of-the-art modified ABC algorithms do. 

PMID- 24892108
TI  - Editorial: on clinical guidelines.

PMID- 24892111
TI  - Surgical treatment of single gingival recessions: clinical guidelines.
AB  - PURPOSE: The purpose of this clinical guidelines project was to determine the
      most appropriate surgical techniques, in terms of efficacy, complications, and
      patient opinions, for the treatment of buccal single gingival recessions without
      loss of interproximal soft and hard tissues. METHODS: Literature searches were
      performed (electronically and manually) for entries up to 28 February, 2013
      concerning the surgical approaches for the treatment of gingival recessions.
      Systematic reviews (SRs) of randomised controlled trials (RCTs) and individual
      RCTs that reported at least 6 months of follow-up of surgical treatment of single
      gingival recessions were included. The full texts of the selected SRs and RCTs
      were analysed using checklists for qualitative evaluation according to the
      Scottish Intercollegiate Guidelines Network (SIGN) method. The following
      variables were evaluated: Complete Root Coverage (CRC); Recession Reduction
      (RecRed); complications; functional and aesthetic satisfaction of the patients;
      and costs of therapies. RESULTS: Out of 30 systematic reviews, 3 SRs and 16 out
      of 313 RCTs were judged to have a low risk for bias (SIGN code: 1+). At a short
      term evaluation, the coronally advanced flap plus connective tissue graft method
      (CAF+CTG) resulted in the best treatment in terms of CRC and/or RecRed; in case
      of cervical abrasion and presence of root sensitivity CAF + CTG + Restoration
      caused less sensitivity than CAF+CTG. CAF produced less postoperative discomfort
      for patients. Limited information is available regarding postoperative dental
      hypersensitivity and aesthetic satisfaction of the patients. CONCLUSION: In
      presence of aesthetic demands or tooth hypersensitivity, the best way to
      surgically treat single gingival recessions without loss of interproximal tissues
      is achieved using the CAF procedure associated with CTG. Considering
      postoperative discomfort, the CAF procedure is the less painful surgical
      approach, while the level of aesthetic satisfaction resulted higher after CAF
      either alone or with CTG. It is unclear how much tooth hypersensitivity is
      reduced by surgically covering buccal recessions. It is important to note that
      the present recommendations are based on short-term data (less than 1 year).
      SOURCE OF FUNDING: The guidelines project was made possible through self
      financing by the authors.

PMID- 24892113
TI  - Three-year post-loading results of a randomised, controlled, split-mouth trial
      comparing implants with different prosthetic interfaces and design in partially
      posterior edentulous mandibles.
AB  - PURPOSE: To compare the clinical and radiological outcomes of two implant designs
      with different prosthetic interfaces and neck configurations. MATERIALS AND
      METHODS: Thirty-four partially edentate patients randomly received at least one
      NobelActive implant (Nobel Biocare, Goteborg, Sweden) with back-tapered collar,
      internal conical connection and platform shifting design, and one NobelSpeedy
      implant (Nobel Biocare) with external hexagon and flat-to-flat implant-abutment
      interface according to a split-mouth design. Follow-up continued to 3 years post
      loading. The primary outcome measures were the success rates of the implants and
      prostheses, and the occurrence of any surgical and prosthetic complications
      during the entire follow-up. Secondary outcome measures were: horizontal and
      vertical peri-implant marginal bone level (MBL) changes, resonance frequency
      analysis values at implant placement and loading (4 months), sulcus bleeding
      index (SBI) and plaque score (PS). RESULTS: No drop-out occurred. No implants and
      prostheses failures were observed to the 3-year follow-up. MBL changes were
      statistically significant different with better results for the NobelActive
      implants for both horizontal and vertical measurements (P = 0.000). After 3 years
      post-loading, the NobelActive implants underwent a mean vertical bone resorption
      of 0.66 mm, compared with 1.25 mm for the NobelSpeedy Groovy implants (P =
      0.000); the mean horizontal bone resorption was 0.19 mm for the NobelActive
      implants and 0.60 mm for the NobelSpeedy Groovy implants (P = 0.000). A high ISQ
      value was found for both implants, and no statistically significant difference
      was found for ISQ mean values between interventions (P = 0.941 at baseline; P =
      0.454 at implantabutment connection; P = 0.120 at prosthesis delivery). All
      implants showed good periodontal health at the 3-year-in-function visit, with no
      significant differences between groups. CONCLUSION: The results of this research
      suggest that in well-maintained patients, the MBL changes could be affected by
      the different implant design. After 4 months of unloaded healing, as well as
      after 3 years in function, both implants provided good results, however vertical
      and horizontal bone loss had statistically significant differences between the
      two groups (difference of 0.58 +/- 0.10 mm for the vertical MBL, and 0.4 +/- 0.05
      mm for the horizontal MBL), with lower values in the Nobel Active implants,
      compared to the NobelSpeedy Groovy implants.

PMID- 24892114
TI  - 1-stage versus 2-stage lateral sinus lift procedures: 1-year post-loading results
      of a multicentre randomised controlled trial.
AB  - PURPOSE: To compare the efficacy of 1-stage versus 2-stage lateral maxillary
      sinus lift procedures. MATERIALS AND METHODS: Sixty partially edentulous patients
      requiring 1 to 3 implants and having 1 to 3 mm of residual bone height and at
      least 5 mm bone width below the maxillary sinus, as measured on CT scans were
      selected. They were randomised according to a parallel group study design into
      two equal arms to receive either a 1-stage lateral window sinus lift with
      simultaneous implant placement or a 2-stage procedure with implant placement
      delayed by 4 months, using a bone substitute in three different centres. Implants
      were submerged for 4 months, loaded with reinforced provisional prostheses, which
      were replaced, after 4 months, by definitive prostheses. Outcome measures,
      assessed by masked assessors, were: augmentation procedure failures; prosthesis
      failures and implant failures; complications; and marginal peri-implant bone
      level changes. Patients were followed up to 1 year after loading. Only data of
      implants placed in 1 to 3 mm of bone height were reported. RESULTS: Two patients
      dropped out from the 1-stage group and none from the 2-stage group. No sinus lift
      procedure failed in the 1-stage group but one failed in the 2-stage group, the
      difference being not statistically significant (P = 1.00). Two prostheses failed
      or could not be placed in the planned time in the 1-stage group and one in the 2
      stage group, the difference being not statistically significant (P = 0.51). Three
      implants failed in three patients of the 1-stage group, versus one implant in the
      2-stage group, the difference being not statistically significant (P = 0.28). Two
      complications occurred in the 1-stage group and one in the 2-stage group, the
      difference being not statistically significant (P = 0.61). One year after
      loading, 1-stage treated patients lost an average of -1.01 mm (SD: 0.56) of peri
      implant bone and 2-stage sites about -0.93 mm (SD: 0.40). There were no
      statistically significant differences in bone level change between groups 1 year
      after loading (-0.08 mm 95%CI: -0.33 to 0.18 P = 0.56). CONCLUSION: No
      statistically significant differences were observed between implants placed
      according to 1- or 2-stage sinus lift procedures. However this study may suggest
      that in patients having residual bone height between 1 to 3 mm below the
      maxillary sinus, there might be a slightly higher risk for implant failures when
      performing a 1-stage lateral sinus lift procedure.

PMID- 24892115
TI  - Professional oral hygiene procedures do not influence plasma glucose levels in
      systemically healthy individuals: a short-term, randomised, controlled trial.
AB  - PURPOSE: The treatment of gingival inflammation is associated with improved
      glycaemic control in diabetic patients. The goal of this parallel-randomised
      controlled trial (RCT) was to test the shortterm effects of professional oral
      hygiene procedures on plasma glucose levels in systemically healthy individuals.
      MATERIALS AND METHODS: Systemically healthy individuals with gingivitis and no
      sign of periodontitis were enrolled at a private practice in Italy. Patients were
      randomised to either a 1 hour (h) session of professional oral hygiene procedures
      or to 1 h in the waiting room. Not fasting blood glucose levels were assessed by
      a blind examiner at baseline (T0), 1 h (T1) and 2 h (T2) after procedures and
      finally 1 week after (T3). Oral hygiene procedures were then performed also in
      the control group. RESULTS: Twenty patients were randomly allocated to each
      group. There were no drop-outs. Blood glucose levels at T0 (P = 0.0001) and time
      of measurement (P = 0.0001) were statistically significant, while oral hygiene
      procedures were not (mean difference between groups 0.77 mg/dl, 95%CI -2.64
      mg/dl; 4.18 mg/dl, P = 0.6581). Mean blood glucose levels decreased between T0
      and T1, were stable between T1 and T2 and showed similar levels to baseline after
      1 week (T3) for both groups. CONCLUSION: This short-term RCT showed that
      professional oral hygiene procedures were not able to influence plasma glucose
      levels in individuals with gingivitis, but otherwise systemically healthy.

PMID- 24892116
TI  - Immediate loading of two flapless placed mandibular implants supporting cross
      arch fixed prostheses: a 3-year follow-up prospective single cohort study.
AB  - PURPOSE: To evaluate the clinical outcome of two implants placed flapless in
      fully edentulous mandibles and immediately restored with a metal-resin screw
      retained cross-arch prostheses 3 years after loading. MATERIALS AND METHODS:
      Eighty consecutively patients were recruited. Implants for immediate loading had
      to be inserted with a minimum torque of 80 Ncm. Outcome measures, evaluated by
      two independent assessors, were: prosthesis and implant failures, complications,
      marginal bone level changes, implant stability quotient (ISQ) values and patient
      satisfaction. RESULTS: Three years after loading, all prostheses were in function
      although one patient did not come back for the 1- and 3-year follow-ups. Two
      implants failed early in two patients, but were successfully replaced and their
      prostheses remade. Twelve complications occurred in 10 patients but were all
      successfully treated. After 3 years, mean marginal bone loss was 0.43 mm, mean
      ISQ values decreased from 75.4 to 75.3, and all but four patients were fully
      satisfied with the therapy. Four patients were partially satisfied because,
      lacking molars, they could not chew as they wished. CONCLUSION: Immediately
      loaded mandibular cross-arch partial dentures can be supported by only two dental
      implants up to 3 years. Longer follow-ups (around 10 years) are needed to know
      the prognosis of this treatment modality.

PMID- 24892118
TI  - Microtensile bond strength test bias caused by variations in bonded areas.
AB  - PURPOSE: While it has been shown that no method produces specimens with exactly
      the same cross-sectional bonded area (BA), BA variations within and between
      studies are a well-known covariate in microtensile test results. However, no
      method has yet been described to accurately account for its influence. A
      procedure is presented that allows controlling for variations of BA effects on
      results. Further, a proposal for reporting is presented which enables results of
      different studies to be compared. MATERIALS AND METHODS: Partially using the
      results of the report in which the microtensile test was originally described,
      144 both general (caused by differences in BA) and specific (due to a material's
      performance differences and intrinsic biological variability of specimens)
      variabilities were separated through linear regression of microtensile (MPa) to
      BA (mm2) pooled results. Comparing the specific variability of specimens - the
      residuals to the regression line - of groups allowed assessing differences
      between groups. RESULTS: A means comparison of residuals showed that specific
      differences were significant (t-test, p = 0.0004). The null hypothesis could be
      rejected: materials' performances were different. This could not be determined in
      the original report, since BA variability was very high. A proposal for reporting
      of results to facilitate their clinical interpretation and comparison between
      studies is presented. CONCLUSION: Controlling for general variability caused by
      differences in BA size allows precise comparison of microtensile tests results.

PMID- 24892119
TI  - Mechanical properties and bonding potential of partially stabilized zirconia
      treated with different chemomechanical treatments.
AB  - PURPOSE: To evaluate the effect of different chemomechanical surface treatments
      of zirconia on fracture toughness, flexural strength, bond strength of zirconia
      to composite cement, surface topography, and phase transformation. MATERIALS AND
      METHODS: Pre-sintered yttrium-stabilized zirconium oxide blocks (in Coris ZI)
      were used. Specimens were prepared using a milling machine (Cerec InLab).
      Specimens for each testing procedure were classified into 6 groups according to
      the surface treatment applied: group 1: air-borne particle abrasion (ABA); group
      2: silica coating; group 3: hot etching solution; group 4: hot etching solution
      followed by ABA; group V: hot etching solution followed by silica coating; group
      6: control. Fracture toughness, biaxial flexural strength, and shear bond
      strength were tested using a universal testing machine. Surface topography was
      evaluated using a surface roughness tester and scanning electron microscope.
      Phase transformation was examined using x-ray diffraction analysis. Data were
      subjected to one-way ANOVA followed by Tukey's HSD multiple comparisons test at p
      < 0.05. The strength reliability was analyzed using the Weibull distribution.
      RESULTS: Silica coating revealed the highest mean fracture toughness (9.18 +/-
      0.11 MPa * m1/2), biaxial flexural strength (1614.1 +/- 124.6 MPa), and bond
      strength value (31.5 +/- 5.06 MPa) among all tested groups. Surface topography
      evaluation revealed variations among the different surface-treated groups.
      CONCLUSIONS: Silica coating induced significant improvement in the tested
      properties compared to other treatments. The use of combined treatment of hot
      etching solution followed by either air-borne particle abrasion or silica coating
      of the zirconia surface did not provide an added advantage over silica coating
      alone.

PMID- 24892120
TI  - Ferric sulphate alterations on primary dentin and the adhesive interface.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that the pulp
      medication ferric sulphate (FS) may remain on primary dentin, affecting its
      microchemical structure and the bond strength of adhesives to primary dentin.
      MATERIALS AND METHODS: The effects of FS and pre-bonding conditioning (37%
      phosphoric acid [PA] for 15 s or a self-etching primer, with or without the use
      of 2% chlorhexidine [CHX]) on FS-treated primary dentin were characterized using
      optical microscopy with Masson's and Perls' stains, variable-pressure SEM/energy
      dispersive x-ray spectroscopy (VP-SEM/EDS), Fourier transform infrared
      spectroscopy (FT-IR), and x-ray diffraction. Ferric sulphate was applied for 30 s
      or 1 h for microchemical analysis. The adhesive interface and the bond strength
      were studied by VP-SEM/EDS and the MUTBS test (1 mm2 bars, crosshead speed 0.5
      mm/min), respectively. The study groups were: etch-and-rinse (E&R, Excite)
      adhesive (group 1); FS+E&R (group 2); FS+CHX+E&R (group 3); self-etching (SE,
      Adper Scotchbond) adhesive (group 4); FS+SE (group 5); FS+CHX+SE (group 6).
      RESULTS: Ferric sulphate application produced demineralization, gypsum formation,
      and adsorption of Fe on the dentin surface, and it modified the collagen
      structure of primary dentin. There were no effects of FS on bond strength of the
      tested etch-and-rinse adhesive system. FS slightly reduced the bond strength
      between the primary dentin and the SE adhesive, and the values were not restored
      by CHX (group 4 = 17.58 +/- 5.52 MPa > group 5 = 14.26 +/- 7.08 MPa = group 6 =
      13.96 +/- 4.87 MPa). CONCLUSIONS: Ferric sulphate alters the microchemical
      structure of primary dentin and can impair the adhesive strength of some self
      etching adhesives.

PMID- 24892121
TI  - Influence of different test parameters on the microshear bond strength of two
      simplified etch-and-rinse adhesives.
AB  - PURPOSE: To evaluate the effect of different test parameters on the resin-dentin
      microshear bond strength (MUSBS). MATERIALS AND METHODS: A 1.5-mm-thick dentin
      disk was prepared in each of 140 human molars. The disks were divided into five
      groups to test the following variables: time of adhesive light polymerization (n
      = 20), storage time (n = 40), bonding area (n = 40), Tygon tube removal (n = 20),
      and time of composite placement (n = 20). The adhesives were applied and each
      specimen was subjected to MUSBS testing. All fractured specimens were observed
      with SEM. The data from each experiment were subjected to two-way ANOVA and
      Tukey's test (alpha = 0.05). RESULTS: The storage time, bonding area, and Tygon
      tube removal did not influence the MUSBS. Higher MUSBS values were found when
      empty Tygon tubes were filled after positioning and when the adhesive was light
      polymerized before Tygon tube placement (p < 0.05). CONCLUSIONS: Differences in
      test parameters affected the MUSBS of adhesives, especially the time of adhesive
      light polymerization and composite placement.

PMID- 24892122
TI  - Influence of QMix irrigant on the micropush-out bond strength of biodentine and
      white mineral trioxide aggregate.
AB  - PURPOSE: To evaluate the effect of QMix and other conventional endodontic
      irrigants on the micropush-out bond strength of Biodentine (BD) and white mineral
      trioxide aggregate (WMTA). MATERIALS AND METHODS: One hundred eighty midroot
      dentin slices with a thickness of 1.0 mm were prepared. BD and WMTA were placed
      inside the lumens of the root slices (n = 90). Then the specimens of each
      material were divided into 6 groups (n = 15) according to irrigation solution
      (saline, 5.25% NaOCl, 2% CHX, 17% EDTA, or QMix) immersed in the same for 30 min.
      For the control group, a wet cotton pellet was placed over the specimen. After
      that, the micropush-out bond strength was determined using a universal testing
      machine, and the bond failure mode was determined using a stereomicroscope. The
      morphological microstructures of specimens were evaluated with scanning electron
      microscopy (SEM). Data were analyzed using ANOVA and Tukey's post-hoc test.
      RESULTS: BD revealed higher bond strength than WMTA (p < 0.05). WMTA was
      significantly affected after exposure to 2% CHX solution. QMix irrigant did not
      compromise the bond strength of BD or WMTA. Most failures for BD were cohesive,
      while for WMTA, adhesive failures were the predominant type. A substantial change
      in the microstructure of BD and WMTA occurred after exposure to different
      irrigation solutions. CONCLUSIONS: QMix did not affect the bond strength of BD or
      WMTA. BD showed higher resistance than WMTA to dislodgement forces from root
      dentin.

PMID- 24892123
TI  - Variability, regulation and clinical practice.

PMID- 24892124
TI  - 'But my patients are sicker!'.

PMID- 24892125
TI  - Measuring unexplained variation in acute hospital use by patients enrolled with
      northern New Zealand general practices.
AB  - INTRODUCTION: There is increasing concern worldwide at the steady growth in acute
      inpatient admissions and emergency department (ED) attendances. AIM: To develop
      measures of variation in acute hospital use between populations enrolled at
      different general practices that are independent of the sociodemographic
      characteristics of those populations. METHODS: Two consecutive years of hospital
      discharge and ED attendance data were combined with primary health organisation
      (PHO) registers from 385 practices of over 1.5 million people to develop and test
      two measures of unplanned hospital use: the standardised acute hospital admission
      ratio (SAAR) and the standardised ED attendance ratio (SEAR). Disease-specific
      measures were also produced for inpatient events. RESULTS: The enrolled
      populations of a high proportion of practices had significantly higher or lower
      than expected acute use of hospitals and this was consistent over both years
      studied. Practices whose population made unexpectedly high use of acute hospital
      care for one condition tended to do so for others. Differences in health needs
      between practice populations as measured by clinical complexity, comorbidities
      and length of stay did not explain a significant portion of the overall variation
      in hospital admissions. The enrolled population's average travelling time to a 24
      hour ED accounted for some of the practice variation in unplanned utilisation of
      hospital services. DISCUSSION: This study confirms that there is considerable
      unexplained practice variation in acute hospital use. Further development of the
      SAAR and SEAR measures may be possible to use these to identify modifiable
      practice-level factors associated with high unplanned hospital use.

PMID- 24892126
TI  - Impact of an undergraduate course on medical students' self-perceived nutrition
      intake and self-efficacy to improve their health behaviours and counselling
      practices.
AB  - INTRODUCTION: Doctors are increasingly involved in the management of chronic
      disease and counsel patients about their lifestyle behaviours, including
      nutrition, to improve their health outcomes. AIM: This study aimed to assess the
      impact of a medical undergraduate course containing nutrition content on medical
      students' self-perceived nutrition intake and self-efficacy to improve their
      health behaviours and counselling practices. METHODS: A total of 239 medical
      students enrolled in a 12-week nutrition-related course at The University of
      Auckland were invited to complete an anonymous questionnaire before and after the
      course. The questionnaire was adapted from a previous evaluation of a preventive
      medicine and nutrition course at Harvard Medical School. RESULTS: Sixty-one
      medical students completed both pre- and post-course questionnaires (25.5%). At
      baseline, medical students described their eating habits to be more healthy than
      non-medical students (p=0.0261). Post-course, medical students reported a higher
      frequency of whole-grain food intake (p=0.0229). Medical students also reported
      being less comfortable making nutrition recommendations to family and friends
      post-course (p=0.008). Most medical students (63.9%) perceived increased
      awareness of their own dietary choices, and some (15.3%) reported an increased
      likelihood to counsel patients on lifestyle behaviour post-course. DISCUSSION:
      Students can increase awareness of their own nutrition behaviour after
      undertaking a course that includes nutrition in the initial phase of their
      medical degree. Further investigation of how medical students' confidence to
      provide nutrition advice evolves throughout their training and in future practice
      is required.

PMID- 24892128
TI  - Objective benefits, participant perceptions and retention rates of a New Zealand
      community-based, older-adult exercise programme.
AB  - INTRODUCTION: Most exercise studies for older adults have been university- or
      hospital-based. Little is known about the benefits and factors influencing long
      term participation in community-based exercise programmes, especially in New
      Zealand. AIM: To quantify the objective benefits, participant perceptions and
      retention rates of a New Zealand community-based exercise programme for adults
      (60 years or older). METHODS: Study 1 involved assessing the benefits of 12
      weeks' training on a convenience sample of 62 older adults commencing the
      never2old Active Ageing programme. Study 2 assessed the perceptions of 150
      current participants on a variety of programme components that could act as
      barriers or facilitators to continued engagement. Study 3 assessed the retention
      rates of 264 participants in the programme over a two-year period. RESULTS:
      Significant improvements in many physical functional scores were observed in
      Study 1 (5-30 percentile points; p<0.05). Questionnaire responses from
      participants in Study 2 indicated many perceived benefits (positive responses
      from 67-95% on various questions) and that core components of the programme were
      rated very highly (64-99% on various components). Retention rates were high, with
      Study 3 finding 57% of participants still engaging in the programme at the end of
      the two-year period. DISCUSSION: A community-based exercise programme for older
      adults can improve many objective and subjective measures of physical fitness and
      functional performance and have good retention rates. General practitioners and
      other allied health professionals in New Zealand should consider promoting
      programmes, such as the never2old Active Ageing programme, to their older
      patients.

PMID- 24892129
TI  - Change in a child's naevus prompts referral to a dermatology service.
AB  - INTRODUCTION: Although melanoma is rare in children, parental concern about skin
      lesions often results in specialist referral and/or excision of benign lesions.
      AIM: To review dermatology referrals of children with skin lesions to determine
      reason for referral, macroscopic and dermatoscopic features of referred lesions,
      diagnosis, management and histology for excised lesions. METHODS: Referral
      letters, clinical and dermatoscopic images and outcomes were reviewed for skin
      lesions in children aged 0-18 years attending a teledermoscopy clinic over a 28
      month period. RESULTS: Eighty-nine children with 128 lesions accounted for 9% of
      all referrals to the teledermoscopy clinic. The mean age of the children was 12
      years (range 2-18 years). A 'changing mole' was the most common reason for
      referral (35 children; 39%), followed by 'possible melanoma' (19; 21%), and
      congenital naevus (9; 10%). The majority of lesions were benign melanocytic naevi
      (112 lesions; 88%). No lesions were diagnosed as melanoma or non-melanoma skin
      cancer. A history of change was given for 61/112 lesions (54%). Five lesions were
      excised; histopathological diagnoses were two spindle cell tumours of Reed, two
      compound naevi and one Spitz naevus. DISCUSSION: Change in a lesion, though a
      common trigger for referral, is less likely to indicate malignancy in children
      compared with adults and, as a sole criterion, does not necessitate specialist
      referral. Teledermoscopy clinics offer high quality macroscopic and dermatoscopic
      images and can assist in providing reassurance, where appropriate.

PMID- 24892127
TI  - Herpes zoster: when do patients present and who gets antiviral treatment?
AB  - INTRODUCTION: Herpes zoster and its sequelae can have a serious impact on quality
      of life, particularly in the elderly. The duration and severity of herpes zoster
      symptoms can be reduced with antiviral treatment. Early treatment is most
      effective. AIM: To identify how soon after onset of herpes zoster symptoms adults
      presented to a suburban Dunedin general practice and to describe which patients
      received antiviral treatment. METHODS: Adult herpes zoster cases were identified
      from a large suburban general practice from 2004 to 2009. Duration of symptoms at
      presentation and antiviral prescription were identified from medical records and
      described by patient characteristics. RESULTS: We identified 278 incident cases.
      Approximately one-third presented within three days of symptoms, one-third after
      three days, and in one-third of cases the duration of symptoms was not
      documented. A higher percentage of patients with ophthalmic herpes zoster
      presented within three days (45%), while a lower percentage of men (24%) and
      patients from the lowest socioeconomic quintile (25%) presented within three
      days. Most incident cases received antiviral treatment. A higher percentage of
      patients with ophthalmic herpes zoster and patients who presented within three
      days of symptoms received antiviral treatment. Some patients who presented after
      seven days of symptoms also received treatment. Antiviral prescribing did not
      increase with patient age. DISCUSSION: Despite many adults with acute herpes
      zoster presenting after three days of symptoms, most received antiviral
      treatment. It is not known why many presented late. It is not known whether late
      treatment is effective.

PMID- 24892130
TI  - A piece of the jigsaw of primary care: health professional perceptions of an
      integrated care model of hepatitis C management in the community.
AB  - INTRODUCTION: There is growing interest in increasing uptake of hepatitis C (HCV)
      treatment. HCV is strongly associated with injecting drug use and is a
      stigmatised illness. People with HCV may be reluctant to engage with health care
      services. A community-based, nurse-led integrated care clinic was established in
      Christchurch, New Zealand with the intention of bridging the health care gap for
      those unwilling or unable to access mainstream health care. This paper explores
      the experiences and perceptions of health professionals regarding the
      implementation of this clinic, with particular attention paid to the
      interprofessional relationships relevant to the clinic. METHODS: Qualitative, in
      depth interviews were conducted with 24 stakeholders, including four staff of the
      clinic and other service providers with varying relationships to the clinic.
      FINDINGS: Participants generally endorsed the clinic model and described its
      operation as easy to access, non-judgmental and non-threatening, and, therefore,
      able to attract and engage 'hard-to-reach' clients. The clinic model was also
      thought to support more effective use of health resources. Some participants
      expressed concerns regarding the potential 'poaching' of patients from other
      services (particularly general practice) and indicated a preference for HCV
      treatment services to be restricted to hospital settings. CONCLUSION: The
      findings of this study suggest the need to address concerns of general
      practitioners regarding patient poaching. Key information to disseminate is the
      clinic's success in engaging with complex clients and contribution to more
      efficacious use of health service resources. These activities may require the
      advocacy of a key local opinion leader acting as 'knowledge broker'.

PMID- 24892131
TI  - Breast cancer and breast screening: perceptions of Chinese migrant women living
      in New Zealand.
AB  - INTRODUCTION: Migrant Chinese constitute a significant and increasing proportion
      of New Zealand women. They have lower rates of participation in breast cancer
      screening than other New Zealanders, but reasons for this are unknown. The aim of
      this study was to investigate factors affecting Chinese women's understanding of,
      and access to, breast health services, to better understand reasons for low
      participation in screening and their experiences of breast cancer clinic care.
      METHODS: The participants were 26 Chinese migrant women-19 recruited in the
      community and seven recruited from 17 eligible women attending a breast clinic
      between 2008 and 2010 in Wellington, New Zealand. The design was that of a
      qualitative study, using semi-structured interviews and thematic content
      analysis. FINDINGS: There were low levels of awareness about the national breast
      screening programme and limited engagement with preventive primary care services.
      Concerns about privacy and a range of communication difficulties were identified
      that related to oral language, lack of written information in Chinese, and
      limited understanding about Chinese perceptions of ill health and traditional
      Chinese medicine by New Zealand health professionals. CONCLUSION: Addressing
      communication barriers for Chinese migrant women has the potential to raise
      awareness about breast cancer and breast health, and to increase successful
      participation in breast cancer screening. Greater efforts are needed to ensure
      this group has an understanding of, and is engaged with a primary care provider.
      Such efforts are key to improving health for this growing sector of the New
      Zealand population.

PMID- 24892132
TI  - Direct observation of the nutrition care practices of Australian general
      practitioners.
AB  - INTRODUCTION: Nutrition care refers to nutrition-related advice or counselling
      provided by health professionals in an attempt to improve the nutrition behaviour
      of patients. AIM: The aim of this study was to describe the practices of a sample
      of Australian general practitioners (GPs) when providing nutrition care to adult
      patients. METHODS: Eighteen GPs (13 male, 5 female) were observed by fourth-year
      medical students during their general practice rotation. Each GP was observed for
      five consultations that included nutrition care, totalling 90 observed
      consultations. In each consultation, students completed a 31-item nutrition care
      checklist of nutrition care practices that could feasibly occur in a standard
      consultation. Each practice was marked with either a 'yes' (completed), 'no' (did
      not complete) or 'completed by practice nurse prior to or after the
      consultation'. RESULTS: Twenty-eight nutrition care practices were observed at
      least once. The most frequently observed practices were measuring and discussing
      blood pressure (76.7%; n=69), followed by general questions about current diet
      (74.4%; n=67). Approximately half of the consultations included a statement of a
      nutrition-related problem (52.2%; n=47), and the provision of nutrition advice
      that focused on a nutrient (45.6%; n=41) or food group (52.2%; n=47).
      Consultations with male GPs, as well as GPs with more than 25 years of
      experience, were associated with an increased number of nutrition care practices
      per consultation. DISCUSSION: The GPs performed nutrition care practices in
      varying frequencies. Further research is required to identify the most effective
      GP nutrition care practices to improve the nutrition behaviour of patients.

PMID- 24892133
TI  - The use of bedside ultrasound and community-based paracentesis in a palliative
      care service.
AB  - INTRODUCTION: There is little information, particularly in New Zealand, on the
      use of ultrasound to enhance clinical decision-making in a specialist palliative
      care service. Technological advances have resulted in increasingly portable, user
      friendly ultrasound machines that can be used in the home setting to offer
      convenient access to this treatment option. AIM: To evaluate the clinical use of
      portable ultrasonography in the management of abdominal ascites in a community
      palliative care service. METHODS: Patients referred to the Nurse Maude Hospice
      and Palliative Care Service requiring assessment for abdominal ascites over 12
      months were scanned using a newly purchased handheld ultrasound machine. The
      patients had a variety of diagnoses; the most common diagnosis was ovarian
      cancer. RESULTS: Forty-one ultrasound scans performed for 32 patients to assess
      for ascites drainage were recorded. Fluid was identified in 19 assessments and
      drainage undertaken in 17. Over half the scans were completed at home, allowing
      nine procedures to be performed safely and conveniently, which reduced time spent
      at the local hospital. There were no major complications. DISCUSSION:
      Ultrasonography is a tool that has not previously been utilised in palliative
      care locally, but has significant potential patient benefits. This novel use of
      technology also highlighted potential cost savings to the patient and health
      system, which may be beneficial to other palliative care services in New Zealand.

PMID- 24892134
TI  - General practitioners' views on the role of pedometers in health promotion.
AB  - INTRODUCTION: Regular pedometer use can help initiate and maintain regular
      walking activity that can lead to a number of health-related benefits. The
      primary health care setting has been found to be an ideal venue in which to
      counsel low-active individuals for physical activity. AIM: To examine general
      practitioners' (GPs) views on the role of pedometers in health promotion.
      METHODS: Fifteen GPs working in urban, primary care practices in Auckland, New
      Zealand were individually interviewed. The interview schedule focused on physical
      activity counselling and the Green Prescription programme. For this sub-study,
      the focus was on questions relating to pedometer use. An inductive thematic
      approach was used to analyse the data. FINDINGS: Four main themes were
      identified. Pedometers were viewed as motivational devices that could be used to
      encourage low-active patients to become more active, as they provided feedback on
      step counts. A pedometer was also viewed as a self-management tool, whereby the
      individual could set daily step count goals, which in turn could help increase
      their physical activity engagement. GPs who currently wore a pedometer discussed
      the practicalities of being able to show a patient how to use a pedometer. Also
      discussed was how cost could restrict pedometer access for some patients.
      CONCLUSIONS: Pedometers were viewed by GPs as being helpful devices that could
      help motivate and support low-active patients in becoming more active.
      Information regarding step counts was seen as important because it could make
      people aware how little physical activity they were engaging in.

PMID- 24892135
TI  - Cigarettes should be sold in plain packaging in New Zealand: Yes.

PMID- 24892136
TI  - Cigarettes should be sold in plain packaging in New Zealand: No.

PMID- 24892137
TI  - Regular practice review: promised joy or naught but grief and pain?

PMID- 24892138
TI  - Early childhood caries: a New Zealand perspective.

PMID- 24892139
TI  - Influencing medical students' career decisions.

PMID- 24892140
TI  - Modulatory effects of quercetin and rutin on the activity, expression and
      inducibility of CYP1A1 in intestinal HCT-8 cells.
AB  - Flavonoids, plant secondary metabolites present in fruits and vegetables, show
      antioxidant and anti-tumorigenic effects in vitro, but their poor absorption from
      gastrointestinal tract limits their systemic efficacy in humans. On the other
      hand, flavonoids could protect intestinal cells against carcinogens by their
      potential to inhibit the enzymes metabolizing pre-carcinogenic compounds (e.g.
      CYP1A) to reactive ones. This work was designed to test the effect of quercetin
      (the most abundant flavonoid) and rutin (the most abundant glycosidic form) on
      the activity, expression and inducibility of CYP1A in intestinal HCT-8 cells.
      CYP1A enzymatic activity was measured by ethoxyresorufin-O-deethylase (EROD)
      activity, CYP1A protein expression was detected by western blotting. The effect
      of flavonoids on viability of cells was examined by neutral red uptake test. No
      cytotoxic effect of flavonoids up to 50 MUM concentration was observed. Quercetin
      significantly inhibited EROD activity in the cells, where CYP1A had been
      preinduced by b-naphthoflavone and methylcholanthrene, and it also significantly
      reduced the CYP1A induction mediated by these model inducers. The effect of rutin
      was substantially weaker and mostly in significant in all conducted experiments.
      The results suggest that quercetin may have a potential to limit the CYP1A
      mediated activation of pre-carcinogens in intestinal cells.

PMID- 24892141
TI  - Dedication page to Grant Buchanan.

PMID- 24892142
TI  - Obituary: Adrian C. Begg.

PMID- 24892143
TI  - In Brief: Absorica for acne.

PMID- 24892145
TI  - In lasting tribute: Elliot F. Ellis, MD, 1929-2014.

PMID- 24892146
TI  - Funding the 'H' in NHMRC.

PMID- 24892147
TI  - Asylum seeker health and bridging visas: history repeating.

PMID- 24892148
TI  - Divergent mortality trends by ethnicity in Fiji.
AB  - OBJECTIVE: To examine trends in infant mortality rate (IMR), adult mortality and
      life expectancy (LE) in the two major Fijian ethnic groups since 1975. METHODS:
      Estimates of IMR, adult mortality (15-59 years) and LE by ethnicity are
      calculated from previously unreported Fiji Ministry of Health data and extracted
      from published sources. RESULTS: Over 1975-2008: IMR decreased from 33 to 20
      deaths/1,000 live births in i-Taukei (Fiji Melanesians); and 38 to 18 in Fijians
      of Indian descent. Increased adult male mortality among i-Taukei and decline
      among Fijians of Indian descent led to an equal probability of dying in 2007 of
      29%; while in female adults the probability trended upwards in i-Taukei to 25%,
      and declined in Fijians of Indian descent to 17%. Life expectancy in both
      ethnicities increased until 1985 (to 64 years for males; 68 for females) then
      forming a plateau in males of both ethnicities, and Fijian females of Indian
      descent, but declining in i-Taukei females to 66 years in 2007. CONCLUSIONS:
      Despite IMR declines over 1975-2008, LE for i-Taukei and Fijians of Indian
      descent has not increased since 1985, and has actually decreased in i-Taukei
      women, consistent with trends in adult mortality (15-59 years). Mortality
      analyses in Fiji that consider the entire population mask divergent trends in the
      major ethnic groups. This situation is most likely a consequence of non
      communicable disease mortality, requiring further assessment and a strengthened
      response.

PMID- 24892149
TI  - An examination of smoking initiation rates by age: results from a large
      longitudinal study in New Zealand.
AB  - OBJECTIVE: Investigations of smoking initiation often focus on the experiences of
      children and youth. However, prevalence data from the Tobacco Use Surveys (TUS)
      and the New Zealand (NZ) census suggest substantial uptake of smoking occurs
      after 15 years of age, including among young adults aged 18-24 years. Identifying
      initiation rates is difficult using cross-sectional prevalence data, particularly
      among older age groups, which are subject to cohort effects and where quitting
      and premature mortality reduce prevalence. We aimed to identify initiation rates
      using a prospective study design. METHODS: The SoFIE-Health longitudinal survey
      included 15,095 subjects aged 15 years or older who responded in the three years
      that include the health module: 2004/05, 2006/07 and 2008/09. We calculated the
      proportion of 'never smokers' who became regular smokers (initiation) by age at
      baseline. RESULTS: Initiation between 2004/05 and 2008/09 was 14.2% for 15-17
      year olds, 7.0% for 18-19 years, 3.1% for 20-24 years and 1.4% for 25-34 years,
      with low levels of initiation (<1.0%) among older age groups. CONCLUSIONS: There
      were strong age-related gradients in smoking initiation. Substantial initiation
      occurs among older youth and young adults, but is rare after age 24.
      IMPLICATIONS: Efforts to prevent initiation of smoking should focus not only on
      adolescents but also on older youth and young adults.

PMID- 24892150
TI  - Incidence and management of hepatocellular carcinoma among Maori and non-Maori
      New Zealanders.
AB  - OBJECTIVE: To investigate time trends in hepatocellular carcinoma (HCC) incidence
      disparities, and ethnic differences in risk factors, comorbidity and treatment
      pathways among HCC patients. METHODS: Cohorts of the NZ population (1981-2004)
      were created and probabilistically linked to cancer registry records to
      investigate trends in incidence by ethnicity over time. Hospital notes of 97
      Maori and 92 non-Maori HCC patients diagnosed between 01/01/2006 and 31/12/2008
      in NZ's North Island were reviewed. RESULTS: Liver cancer incidence was higher
      among Maori for all time periods. Compared with non-Maori, Maori males had nearly
      five times the rate of liver cancer (pooled RR=4.79, 95% CI 4.14-5.54), and Maori
      females three times the rate (pooled RR= 3.02, 95% CI 2.33-3.92). There were no
      significant differences in tumour characteristics or treatment of Maori and non
      Maori patients with HCC. Maori more commonly had hypertension (51% versus 25%)
      while more non-Maori had cirrhosis recorded (62% versus 41%). The prevalence of
      hepatitis B among Maori patients (56%; 95% CI 45%-67%) was more than double that
      of non-Maori (27%; 95% CI 19%-36%). The hazard ratio for cancer-specific death
      for Maori compared with non-Maori was 1.36 (95% CI 0.96-1.92). CONCLUSIONS AND
      IMPLICATIONS: HCC remains an important health problem particularly for Maori men.
      Efforts to improve coverage of screening for hepatitis B and surveillance of
      those with chronic hepatitis should be a priority to address the large
      inequalities found in liver cancer epidemiology.

PMID- 24892151
TI  - Exploring risk factors for suicidal ideation in a population-based sample of New
      Zealand women who have experienced intimate partner violence.
AB  - OBJECTIVE: To explore factors associated with suicidal thoughts among women who
      had experienced intimate partner violence (IPV), using data from the New Zealand
      replication of the WHO Multi-country Violence Against Women study. METHOD: Face
      to-face interviews were conducted. A population-based cluster sampling scheme
      with a fixed number of dwellings per cluster was employed. Logistic regression
      was conducted to identify those variables independently associated with suicidal
      ideation. RESULTS: Women who had experienced IPV were more likely to report they
      had thought about taking their own life if they: reported that their partner's
      behaviour had impacted on their mental health (OR = 4.81, 95% CI 3.30-7.01); were
      current or former users of recreational drugs (OR=1.94, 95% CI 1.43-2.64); had
      experienced a stillbirth/abortion/miscarriage (OR=1.93, 95% CI 1.44-2.58); and
      had experienced emotional abuse in the previous 12 months (OR=1.40, 95% CI 1.00
      1.96). CONCLUSION AND IMPLICATIONS: This study corroborates international
      findings that women's experience of IPV is associated with increased risk of
      suicidal thoughts. While the results point to the need for all health care
      providers to routinely enquire about intimate partner violence among their
      patients, they also argue for the need for health care providers to be aware of,
      and equipped to respond to, the mental health needs of their clients. The results
      also indicate that there is a need for mental health services to assess for, and
      respond to intimate partner violence among women presenting with suicidal
      ideation.

PMID- 24892152
TI  - Characteristics of health impact assessments reported in Australia and New
      Zealand 2005-2009.
AB  - OBJECTIVE: To describe the use and reporting of Health Impact Assessment (HIA) in
      Australia and New Zealand between 2005 and 2009. METHODS: We identified 115 HIAs
      undertaken in Australia and New Zealand between 2005 and 2009. We reviewed 55
      HIAs meeting the study's inclusion criteria to identify characteristics and
      appraise the quality of the reports. RESULTS: Of the 55 HIAs, 31 were undertaken
      in Australia and 24 in New Zealand. The HIAs were undertaken on plans (31),
      projects (12), programs (6) and policies (6). Compared to Australia, a higher
      proportion of New Zealand HIAs were on policies and plans and were rapid
      assessments done voluntarily to support decision-making. In both countries, most
      HIAs were on land use planning proposals. Overall, 65% of HIA reports were judged
      to be adequate. CONCLUSION: This study is the first attempt to empirically
      investigate the nature of the broad range of HIAs done in Australia and New
      Zealand and has highlighted the emergence of HIA as a growing area of public
      health practice. It identifies areas where current practice could be improved and
      provides a baseline against which future HIA developments can be assessed.
      IMPLICATIONS: There is evidence that HIA is becoming a part of public health
      practice in Australia and New Zealand across a wide range of policies, plans and
      projects. The assessment of quality of reports allows the development of
      practical suggestions on ways current practice may be improved. The growth of HIA
      will depend on ongoing organisation and workforce development in both countries.

PMID- 24892153
TI  - Noticing pesticide spray drift from agricultural pesticide application areas and
      breast cancer: a case-control study.
AB  - OBJECTIVES: To examine the relationship between self-reported noticing of
      pesticide spray drift from agricultural areas and breast cancer. METHODS: A case
      control study of breast cancer was conducted in Western Australia from 2009 to
      2011. Awareness of pesticide spray drift from agricultural areas was assessed by
      a self-report of whether the participant had noticed spray drift. To evaluate
      recall bias, we stratified the analysis by participants' belief about whether
      pesticides increase the risk of breast cancer. Unconditional logistic regression
      was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). This
      analysis included 1,743 controls and 1,169 cases. Sensitivity analysis for
      potential selection and misclassification bias was also conducted. RESULTS: Among
      women who reported 'ever noticed' pesticide spray drift from agricultural areas,
      an increased risk of breast cancer was also observed (OR=1.43; 95% CI 1.15,
      1.78). A dose response relationship between lifetime exposure to noticing
      pesticide spray drift and risk of breast cancer was observed (p<0.001). An
      increased risk of breast cancer was observed among women who noticed pesticide
      spray drift: initially at the age of 20 or younger (OR=1.61; 95% CI 1.19, 2.16);
      at least 20 years before diagnosis (OR=1.51; 95% CI 1.19, 1.92); and for 10 years
      or more (OR=1.51; 95% CI 1.18, 1.94). CONCLUSION: These findings support the
      hypothesis that women who ever noticed spray drift or who first noticed spray
      drift at a younger age had increased risk of breast cancer.

PMID- 24892154
TI  - Gestational diabetes mellitus in Far North Queensland, Australia, 2004 to 2010:
      midwives' perinatal data most accurate source.
AB  - OBJECTIVES: This study examines the accuracy of Gestational Diabetes Mellitus
      (GDM) case-ascertainment in routinely collected data. METHODS: Retrospective
      cohort study analysed routinely collected data from all births at Cairns Base
      Hospital, Australia, from 1 January 2004 to 31 December 2010 in the Cairns Base
      Hospital Clinical Coding system (CBHCC) and the Queensland Perinatal Data
      Collection (QPDC). GDM case ascertainment in the National Diabetes Services
      Scheme (NDSS) and Cairns Diabetes Centre (CDC) data were compared. RESULTS: From
      2004 to 2010, the specificity of GDM case-ascertainment in the QPDC was 99%. In
      2010, only 2 of 225 additional cases were identified from the CDC and CBHCC,
      suggesting QPDC sensitivity is also over 99%. In comparison, the sensitivity of
      the CBHCC data was 80% during 2004-2010. The sensitivity of CDC data was 74% in
      2010. During 2010, 223 births were coded as GDM in the QPDC, and the NDSS
      registered 247 women with GDM from the same postcodes, suggesting reasonable
      uptake on the NDSS register. However, the proportion of Aboriginal and Torres
      Strait Islander women was lower than expected. CONCLUSION: The accuracy of GDM
      case-ascertainment in the QPDC appears high, with lower accuracy in routinely
      collected hospital and local health service data. This limits capacity of local
      data for planning and evaluation, and developing structured systems to improve
      post-pregnancy care, and may underestimate resources required. IMPLICATIONS: Data
      linkage should be considered to improve accuracy of routinely collected local
      health service data. The accuracy of the NDSS for Aboriginal and Torres Strait
      Islander women requires further evaluation.

PMID- 24892155
TI  - Influences on the degree of preterm birth in New South Wales.
AB  - OBJECTIVE: To identify risk factors for preterm birth and determine if these vary
      by degree of prematurity. METHODS: We used data from the state-wide mandatory
      surveillance system for all births in New South Wales, limiting analysis to the
      836,292 live born, singleton infants without known birth anomaly born from 1994
      to 2004 inclusive. Our main outcome measure was gestational age stratified into
      the clinically relevant groups of: 'term' (37-42 completed weeks gestation);
      'mildly preterm' (33-36 weeks); 'very preterm' (29-32 weeks); and 'extremely
      preterm' (23-28 weeks). Analysis was by multivariate modelling using a
      generalised estimating equations model and confidence intervals adjusted to
      account for the multiple comparisons. RESULTS: Increasing socioeconomic
      disadvantage was associated with increasing risk of having a preterm baby. This
      association strengthened with increasing degree of preterm birth, (adjusted Odds
      Ratio for mothers from the most disadvantaged areas having an 'extremely preterm'
      baby = 1.45 [99.67% CI 1.21-1.75] compared to least disadvantaged areas). Mothers
      who were older, who smoked, were Aboriginal, or had pre-existing diabetes,
      hypertension, or pre-eclampsia were independently more likely to have a preterm
      baby. First-time mothers were more likely to have their baby at term. CONCLUSIONS
      AND IMPLICATIONS: While risk factors for preterm birth such as pre-existing
      medical conditions are treatable, reducing the substantial effects of
      socioeconomic factors on preterm birth presents the greatest potential for
      change. Our data shows that tackling wider social issues will be necessary to
      assist in reducing the rising preterm birth rate.

PMID- 24892156
TI  - Pregnancy intention in an urban Australian antenatal population.
AB  - OBJECTIVE: To determine the prevalence of unintended pregnancy in women
      presenting for antenatal care to a large metropolitan hospital in Sydney,
      Australia, and to investigate health behaviours and demographic factors
      associated with unintended pregnancy. METHODS: From October 2010 to April 2011, a
      self-administered questionnaire covering pregnancy intention, contraceptive use
      and demographic information was given to 1,554 women. A total of 1,218 women
      (78.4%) completed all questions in the validated pregnancy intention instrument.
      RESULTS: Two-thirds of pregnancies (67.6%) were clearly intended, 30.0% were
      ambivalent and more than 2% experienced an unplanned pregnancy. Those more likely
      to experience an unintended pregnancy were women under 25 years old (OR 1.86, 95%
      CI 1.10-3.14), unmarried women (OR 6.08, 95% CI 3.40-10.87) and women of Asian
      background (OR: 2.45, 95% CI 1.76-3.42). More than one-third of women (34.6%) did
      not take any health actions such as stopping smoking before pregnancy.
      CONCLUSIONS: Unintended pregnancies in this population were associated with young
      age, being unmarried and being of Asian background. This study confirms the idea
      that many women do not take health actions before pregnancy. IMPLICATIONS:
      Experts believe that an effective strategy to address unintended pregnancy is to
      improve access to long-acting reversible contraceptives, which do not require
      daily compliance.

PMID- 24892157
TI  - Density of tobacco retail outlets near schools and smoking behaviour among
      secondary school students.
AB  - OBJECTIVE: To investigate whether the density of tobacco retail outlets near
      schools in Victoria, Australia, is associated with adolescent smoking behaviour.
      METHODS: Cross-sectional survey data of 2,044 secondary school students aged 12
      17 years was combined with tobacco outlet audit data. Associations between
      students' self-reported tobacco use and the density of tobacco outlets near
      schools was examined using multilevel logistic and negative binomial regression
      models, with cigarette price at local milk bars and key socio-demographic and
      school-related variables included as covariates. RESULTS: Increased tobacco
      retail outlet density was associated with a significant increase in the number of
      cigarettes smoked in the previous seven days among students who smoked in the
      past month (IRR=1.13; 95% CI 1.02-1.26), but not the odds of smoking in the past
      month in the larger sample (OR=1.06; 95% CI 0.90-1.24), after controlling for
      local mean price of cigarettes and socio-demographic and school-related
      variables. CONCLUSIONS AND IMPLICATIONS: This study suggests there is a positive
      association between tobacco retail outlet density and cigarette consumption among
      adolescent smokers, but not smoking prevalence, in the Australian context. There
      is value in considering policy measures that restrict the supply of tobacco
      retail outlets in school neighbourhoods as a means of reducing youth cigarette
      consumption.

PMID- 24892144
TI  - Classification of childhood asthma phenotypes and long-term clinical responses to
      inhaled anti-inflammatory medications.
AB  - BACKGROUND: Although recent studies have identified the presence of phenotypic
      clusters in asthmatic patients, the clinical significance and temporal stability
      of these clusters have not been explored. OBJECTIVE: Our aim was to examine the
      clinical relevance and temporal stability of phenotypic clusters in children with
      asthma. METHODS: We applied spectral clustering to clinical data from 1041
      children with asthma participating in the Childhood Asthma Management Program.
      Posttreatment randomization follow-up data collected over 48 months were used to
      determine the effect of these clusters on pulmonary function and treatment
      response to inhaled anti-inflammatory medication. RESULTS: We found 5
      reproducible patient clusters that could be differentiated on the basis of 3
      groups of features: atopic burden, degree of airway obstruction, and history of
      exacerbation. Cluster grouping predicted long-term asthma control, as measured by
      the need for oral prednisone (P < .0001) or additional controller medications (P
      = .001), as well as longitudinal differences in pulmonary function (P < .0001).
      We also found that the 2 clusters with the highest rates of exacerbation had
      different responses to inhaled corticosteroids when compared with the other
      clusters. One cluster demonstrated a positive response to both budesonide (P =
      .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster
      demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P =
      .56) compared with placebo. CONCLUSION: Phenotypic clustering can be used to
      identify longitudinally consistent and clinically relevant patient subgroups,
      with implications for targeted therapeutic strategies and clinical trials design.

PMID- 24892158
TI  - Prevalence and correlates of  overweight and obesity in adult  Australian general
      practice patients.

PMID- 24892159
TI  - Ensuring Indigenous Australians with  acquired brain injuries have equitable 
      access to the National Disability  Insurance Scheme.

PMID- 24892161
TI  - The contribution of financial  hardship, socioeconomic position  and physical
      health to mental health  problems among welfare recipients.

PMID- 24892160
TI  - The provision of integrated care for  people with gambling disorders and  co
      occurring mental health conditions.

PMID- 24892163
TI  - An equitable challenge:  when sustainable development  goals set the post-2015
      agenda.

PMID- 24892162
TI  - An ageing agenda in the post-2015  development framework.

PMID- 24892164
TI  - New Australian Dietary Guidelines  for consumption of dairy products:  are they
      really evidence-based and  does anyone meet them?

PMID- 24892166
TI  - Better organisation of volunteers  in disaster settings is needed:  lessons for
      all from China.

PMID- 24892165
TI  - Hearing loss as a public health matter--why not everyone wants their deafness or
      hearing loss cured.

PMID- 24892167
TI  - [Dear readers].

PMID- 24892168
TI  - [Self-pay benefits or "real life"].

PMID- 24892169
TI  - [Significant increase in cost makes many processes unprofitable].

PMID- 24892170
TI  - [Tax returns: the self-employed can deduct doctors].

PMID- 24892171
TI  - Large drug firms narrow their therapeutic interests.

PMID- 24892172
TI  - Health and science suffer major cuts in Australia's budget.

PMID- 24892173
TI  - In search of sick parrots: Karl Friedrich Meyer, disease detective.

PMID- 24892174
TI  - Charles Farthing.

PMID- 24892175
TI  - Estimating the incremental net health benefit of requirements for cardiovascular
      risk evaluation for diabetes therapies.
AB  - PURPOSE: To evaluate the advantages and disadvantages of pre-approval
      requirements for safety data to detect cardiovascular (CV) risk contained in the
      December 2008 U.S. Food and Drug Administration (FDA) guidance for developing
      type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the
      perspective of diabetes population health. METHODS: We applied the incremental
      net health benefit (INHB) framework to quantify the benefits and risks of
      investigational diabetes drugs using a common survival metric (life-years [LYs]).
      We constructed a decision analytic model for clinical program development
      consistent with the requirements of each guidance and simulated diabetes drugs,
      some of which had elevated CV risk. Assuming constant research budgets, we
      estimate the impact of increased trial size on drugs investigated. We aggregate
      treatment benefit and CV risks for each approved drug over a 35-year horizon
      under each guidance. RESULTS: The quantitative analysis suggests that the
      December 2008 guidance adversely impacts diabetes population health. INHB was 
      1.80 million LYs, attributable to delayed access to diabetes therapies (-0 .18
      million LYs) and fewer drugs (-1.64 million LYs), but partially offset by reduced
      CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses.
      CONCLUSION: The health outcomes impact of all potential benefits and risks should
      be evaluated in a common survival measure, including health gain from avoided
      adverse events, lost health benefits from delayed or for gone efficacious
      products, and impact of alternative policy approaches. Quantitative analysis of
      the December 2008 FDA guidance for diabetes therapies indicates that negative
      impact on patient health will result.

PMID- 24892176
TI  - Guideline application and the real world.

PMID- 24892178
TI  - The hand in art: hands on coins: Iran 1961--Happy coin.

PMID- 24892177
TI  - Future refinement of methotrexate  treatment in rheumatoid arthritis: comment  on
      the article by Yazdany et al.

PMID- 24892179
TI  - Hand made: Freedom.

PMID- 24892180
TI  - Integrated guidance on the care of familial hypercholesterolaemia from the
      International FH Foundation: executive summary.

PMID- 24892181
TI  - [Not Available].

PMID- 24892182
TI  - Dorsal column. From the archives.

PMID- 24892183
TI  - Erratum to: Genetic effect of single-nucleotide polymorphisms in the PPARGC1B
      gene on airway hyperreactivity in asthmatic patients.

PMID- 24892184
TI  - [Health care research for improving quality].

PMID- 24892185
TI  - [Delayed listing as malpractice?].

PMID- 24892186
TI  - Elastic properties of polystyrene nanospheres evaluated with atomic force
      microscopy: size effect and error analysis.
AB  - The mechanical properties of polystyrene (PS) nanospheres of ca. 50-1000 nm in
      diameter were evaluated by using an atomic force microscope (AFM). The
      compressive elastic moduli of individual nanospheres were obtained by analyzing
      the AFM force-displacement curves on the basis of the Hertz and JKR contact
      theories. The results showed that the elastic moduli of PS nanospheres of
      different sizes were in the range of 2-8 GPa. The elastic modulus of PS
      nanospheres increased with the decrease of the sphere diameter, especially when
      the diameter was less than 200 nm. The measurement errors due to tip wear and the
      deformation at the bottom of the sphere were analyzed. Mechanisms for the size
      dependence on the elastic modulus of PS nanospheres were also discussed. 

PMID- 24892187
TI  - Statistical handling of reproduction data for exposure-response modeling.
AB  - Reproduction data collected through standard bioassays are classically analyzed
      by regression in order to fit exposure-response curves and estimate ECx values
      (x% effective concentration). But regression is often misused on such data,
      ignoring statistical issues related to (i) the special nature of reproduction
      data (count data), (ii) a potential inter-replicate variability, and (iii) a
      possible concomitant mortality. This paper offers new insights in dealing with
      those issues. Concerning mortality, particular attention was paid not to waste
      any valuable data-by dropping all the replicates with mortality-or to bias ECx
      values. For that purpose we defined a new covariate summing the observation
      periods during which each individual contributes to the reproduction process.
      This covariate was then used to quantify reproduction-for each replicate at each
      concentration-as a number of offspring per individual-day. We formulated three
      exposure-response models differing by their stochastic part. Those models were
      fitted to four data sets and compared using a Bayesian framework. The individual
      day unit proved to be a suitable approach to use all the available data and
      prevent bias in the estimation of ECx values. Furthermore, a nonclassical
      negative-binomial model was shown to correctly describe the inter-replicate
      variability observed in the studied data sets. 

PMID- 24892188
TI  - Preparation of hollow core/shell microspheres of hematite and its adsorption
      ability for samarium.
AB  - Hollow core/shell hematite microspheres with diameter of ca. 1-2 MUm have been
      successfully achieved by calcining the precursor composite microspheres of pyrite
      and polyvinylpyrrolidone (PVP) in air. The synthesized products were
      characterized by a wide range of techniques including powder X-ray diffraction
      (XRD), field-emission scanning electron microscopy (FESEM), energy-dispersive X
      ray spectroscopy (EDX), transmission electron microscopy (TEM), high-resolution
      TEM (HRTEM), thermogravimetric analysis (TGA) and differential scanning
      calorimetry (DSC), and Brunauer-Emmett-Teller (BET) gas sorptometry. Temperature-
      and time-dependent experiments unveil that the precursor pyrite-PVP composite
      microspheres finally transform into hollow core/shell hematite microspheres in
      air through a multistep process including the oxidation and sulfation of pyrite,
      combustion of PVP occluded in the precursor, desulfation, aggregation, and fusion
      of nanosized hematite as well as mass transportation from the interior to the
      exterior of the microspheres. The formation of the hollow core/shell microspheres
      dominantly depends on the calcination temperature under current experimental
      conditions, and the aggregation of hematite nanocrystals and the core shrinking
      during the oxidation of pyrite are responsible for the formation of the hollow
      structures. Moreover, the adsorption ability of the hematite for Sm(III) was also
      tested. The results exhibit that the hematite microspheres have good adsorption
      activity for trivalent samarium, and that its adsorption capacity strongly
      depends on the pH of the solution, and the maximum adsorption capacity for
      Sm(III) is 14.48 mg/g at neutral pH. As samarium is a typical member of the
      lanthanide series, our results suggest that the hollow hematite microspheres have
      potential application in removal of rare earth elements (REEs) entering the water
      environment. 

PMID- 24892189
TI  - Isoelectric focusing and ELISA for detecting adulteration of donkey milk with cow
      milk.
AB  - Donkey milk has been recently revalued intensely due to its nutritional
      properties. Moreover, donkey milk has been proposed as an effective alternative
      food for some infants with cow milk allergy. Two fast analytical methods were
      proposed to detect the fraudulent practice of blending cow milk to donkey milk.
      Detection of cow alphas1-casein bands along the profiles of experimental donkey
      cow milk mixtures analyzed by isoelectric focusing was adequate to estimate cow
      milk used as adulterant of donkey milk starting from 5% (v/v). An ELISA-based
      method using the antipeptide antibodies raised against the 1-28 sequence stretch
      of cow beta-casein was also developed for an accurate definition of composition
      of donkey-cow milk mixtures. The presence of cow milk at levels as low as 0.5%
      (v/v) was detected in donkey-cow milk mixtures prepared at laboratory scale and
      assayed by ELISA. 

PMID- 24892190
TI  - Homing peptide-conjugated gold nanorods: the effect of amino acid sequence
      display on nanorod uptake and cellular proliferation.
AB  - Gold nanorods (GNRs) have attracted significant interest in the field of medicine
      as theranostic agents for both imaging and photothermal ablation of cancerous
      cells/tissues. Targeting theranostic GNRs specifically to cancer cells is
      necessary to enhance treatment efficacy and minimize undesired side effects. In
      this study, targeting functionalized GNR to EphA2 receptors that are
      overexpressed on prostate cancer cells was investigated as a strategy to achieve
      enhanced GNR uptake by cancer cells. In addition, the influence of targeting
      peptide orientation on functionalized GNR uptake by PC-3 cells was explored. GNRs
      of aspect ratio 4 were functionalized with an EphA2 homing peptide, YSA, using a
      layer-by-layer polypeptide wrapping approach. In parallel, an analogous
      population of YSA-modified GNRs, which display a reversed YSA peptide, with the N
      and C- termini reversed, was also prepared. GC-MS analysis of the YSA-GNRs
      indicated that functionalized GNRs displayed approximately 3000 peptides/GNR. The
      functionalized GNRs remained well-dispersed in biological media for short times
      (<24 h). An increase in GNRs uptake of the YSA-GNRs by PC-3 cells, compared to
      the reversed YSA-GNRs, was observed under identical incubation conditions.
      Lastly, the effect of the YSA-GNRs binding to EphA2 receptors on prostate cancer
      cell proliferation was also studied. The YSA-functionalized GNRs inhibit PC-3
      proliferation at a significantly lower effective dose than free YSA. Overall, the
      polypeptide LBL deposition technique provides a facile route to target
      nanoparticles to overexpressed cellular receptors, with the caveat that the
      specific orientation and display of the targeting moiety plays a critical role in
      the interaction between the nanoparticle and the cell. 

PMID- 24892192
TI  - How can virtual reality interventions help reduce prescription opioid drug
      misuse?

PMID- 24892193
TI  - Personalizing therapy.

PMID- 24892191
TI  - Cortical thinning of the right anterior cingulate cortex in spider phobia: a
      magnetic resonance imaging and spectroscopy study.
AB  - There a lack of consistent neuroimaging data on specific phobia (SP) and a need
      to assess volumetric and metabolic differences in structures implicated in this
      condition. The aim of this study is investigate possible metabolic (via (1)H MRS)
      and cortical thickness abnormalities in spider-phobic patients compared to
      healthy volunteers. Participants were recruited via public advertisement and
      underwent clinical evaluations and MRI scans. The study started in 2010 and the
      investigators involved were not blind in respect to patient groupings. The study
      was conducted at the Ribeirao Preto Medical School University Hospital of the
      University of Sao Paulo, Brazil. Patients with spider phobia (n=19) were matched
      to 17 healthy volunteers with respect to age, education and socio-economic
      status. The spider SP group fulfilled the diagnostic criteria for spider phobia
      according to the Structured Clinical Interview for DSM-IV. None of the
      participants had a history of neurological, psychiatric or other relevant organic
      diseases, use of prescribed psychotropic medication or substance abuse. All
      imaging and spectroscopy data were collected with a 3 T MRI scanner equipped with
      25 mT gradient coils in 30-minute scans. The Freesurfer image analysis package
      and LC Model software were used to analyze data. The hypothesis being tested was
      formulated before the data collection (neural correlates of SP would include the
      amygdala, insula, anterior cingulate gyrus and others). The results indicated the
      absence of metabolic alterations, but thinning of the right anterior cingulate
      cortex (ACC) in the SP group when compared to the healthy control group (mean
      cortical thickness+/-SD: SP=2.11+/-0.45 mm; HC=2.16+/-0.42 mm; t (34)=3.19,
      p=0.001 [-35.45, 71.00, -23.82]). In spectroscopy, the ratios between N
      acetylaspartate and creatine and choline levels were measured. No significant
      effect or correlation was found between MRS metabolites and scores in the Spider
      Phobia Questionnaire and Beck Anxiety Inventory (p>0.05). The ACC is known to be
      related to the cognitive processing of fear and anxiety and to be linked with the
      conditioning circuit. The MRS findings are preliminary and need more studies. The
      finding of reduced ACC thickness in SP is in agreement with evidence from
      previous functional neuroimaging studies and highlights the importance of this
      brain area in the pathophysiology of SP. 

PMID- 24892194
TI  - Virtual reality research continues to progress at the National Institutes of
      Health.

PMID- 24892195
TI  - Psychological factors influencing the effectiveness of virtual reality-based
      analgesia: a systematic review.
AB  - The experience of pain is affected by remarkable psychological factors. The
      concept of neuromatrix suggests that pain is an amalgam of affect, cognition, and
      sensation mediated through diverse brain regions. Moreover, the experience of
      pain appears to be reduced by environmental stimuli that drive attention away
      from the noxious events. Accordingly, immersion in a computer-generated, three
      dimensional virtual environment has been used as an efficient distraction tool in
      a number of studies on pain management. However, no systematic approaches have
      explored the psychological factors that influence the effectiveness of virtual
      reality (VR) as a distraction technology. This review aims to outline the
      fundamental psychological factors involved in the use of VR to provide pain
      management. An analysis of the literature revealed some important elements
      associated with the patients' subjective experience. Eleven studies met the
      inclusion criteria and were included in the review. The results suggest the
      importance of different psychological factors in the effectiveness of the
      analgesic distraction. While sense of presence influence the effectiveness of VR
      as a distraction tool, anxiety as well as positive emotions directly affect the
      experience of pain. Future challenges for pain management via VR include adopting
      properly validated measures to assess psychological factors and using different
      experimental conditions to better understand their complex effects.

PMID- 24892196
TI  - Virtual reality as a distraction technique in chronic pain patients.
AB  - We explored the use of virtual reality distraction techniques for use as
      adjunctive therapy to treat chronic pain. Virtual environments were specifically
      created to provide pleasant and engaging experiences where patients navigated on
      their own through rich and varied simulated worlds. Real-time physiological
      monitoring was used as a guide to determine the effectiveness and sustainability
      of this intervention. Human factors studies showed that virtual navigation is a
      safe and effective method for use with chronic pain patients. Chronic pain
      patients demonstrated significant relief in subjective ratings of pain that
      corresponded to objective measurements in peripheral, noninvasive physiological
      measures.

PMID- 24892197
TI  - Differential effects of two virtual reality interventions: distraction versus
      pain control.
AB  - There is evidence that virtual reality (VR) pain distraction is effective at
      improving pain-related outcomes. However, more research is needed to investigate
      VR environments with other pain-related goals. The main aim of this study was to
      compare the differential effects of two VR environments on a set of pain-related
      and cognitive variables during a cold pressor experiment. One of these
      environments aimed to distract attention away from pain (VRD), whereas the other
      was designed to enhance pain control (VRC). Participants were 77 psychology
      students, who were randomly assigned to one of the following three conditions
      during the cold pressor experiment: (a) VRD, (b) VRC, or (c) Non-VR (control
      condition). Data were collected regarding both pain-related variables (intensity,
      tolerance, threshold, time perception, and pain sensitivity range) and cognitive
      variables (self-efficacy and catastrophizing). Results showed that in comparison
      with the control condition, the VRC intervention significantly increased pain
      tolerance, the pain sensitivity range, and the degree of time underestimation. It
      also increased self-efficacy in tolerating pain and led to a reduction in
      reported helplessness. The VRD intervention significantly increased the pain
      threshold and pain tolerance in comparison with the control condition, but it did
      not affect any of the cognitive variables. Overall, the intervention designed to
      enhance control seems to have a greater effect on the cognitive variables
      assessed. Although these results need to be replicated in further studies, the
      findings suggest that the VRC intervention has considerable potential in terms of
      increasing self-efficacy and modifying the negative thoughts that commonly
      accompany pain problems.

PMID- 24892198
TI  - Clinical use of virtual reality distraction system to reduce anxiety and pain in
      dental procedures.
AB  - Virtual reality (VR) has been used by clinicians to manage pain in clinical
      populations. This study examines the use of VR as a form of distraction for
      dental patients using both subjective and objective measures to determine how a
      VR system affects patients' reported anxiety level, pain level, and physiological
      factors. As predicted, results of self-evaluation questionnaires showed that
      patients experienced less anxiety and pain after undergoing VR treatment.
      Physiological data reported similar trends in decreased anxiety. Overall, the
      favorable subjective and objective responses suggest that VR distraction systems
      can reduce discomfort and pain for patients with mild to moderate fear and
      anxiety.

PMID- 24892199
TI  - Application of virtual body swapping to patients with complex regional pain
      syndrome: a pilot study.
AB  - This study aimed to apply virtual body swapping through mental rehearsal for
      patients with complex regional pain syndrome (CRPS) and to investigate whether it
      is applicable to them. Ten patients who met the diagnostic criterion for CRPS
      type 1 were randomly assigned to either the treatment or control group. All
      participants were asked to watch the virtual body swapping training video clip
      with a head mounted display. The treatment group was additionally asked to assume
      a posture similar to the body on the screen and rehearse the movements mentally,
      as if the body presented on the screen was their body. No difference between the
      groups was found for pain intensity, however, the treatment group showed
      significantly more improvement in body perception disturbance (BPD) after the
      treatment than the control group. Even if the presented study is a preliminary
      one, the above results suggest that virtual body swapping through mental
      rehearsal is applicable for patients with CRPS and may be useful for improving
      BPD. The limitations of the study and the future investigations needed to provide
      clearer clinical suggestions are presented and discussed.

PMID- 24892200
TI  - Virtual reality for pain management in cardiac surgery.
AB  - Surgical anxiety creates psychological and physiological stress, causes
      complications in surgical procedures, and prolongs recovery. Relaxation of
      patients in postoperative intensive care units can moderate patient vital signs
      and reduce discomfort. This experiment explores the use of virtual reality (VR)
      cybertherapy to reduce postoperative distress in patients that have recently
      undergone cardiac surgery. Sixty-seven patients were monitored at IMSS La Raza
      National Medical Center within 24 hours of cardiac surgery. Patients navigated
      through a 30 minute VR simulation designed for pain management. Results were
      analyzed through comparison of pre- and postoperative vital signs and Likert
      scale survey data. A connection was found in several physiological factors with
      subjective responses from the Likert scale survey. Heavy positive correlation
      existed between breathing rate and Likert ratings, and a moderate correlation was
      found between mean arterial pressure and Likert ratings and heart rate and Likert
      ratings, all of which indicated lower pain and stress within patients. Further
      study of these factors resulted in the categorization of patients based upon
      their vital signs and subjective response, providing a context for the
      effectiveness of the therapy to specific groups of patients.

PMID- 24892201
TI  - Virtual reality for the induction of positive emotions in the treatment of
      fibromyalgia: a pilot study over acceptability, satisfaction, and the effect of
      virtual reality on mood.
AB  - One of the most important aspects of fibromyalgia syndrome (FMS) is its impact on
      quality of life, increasing negative emotions and dysfunctional coping
      strategies. One of these strategies is to avoid activities, especially meaningful
      activities, which reduces positive reinforcement. Commencing significant daily
      activities could enable chronic patients to experience a more fulfilling life.
      However, the main difficulty found in FMS patients is their willingness to start
      those activities. Promoting positive emotions could enhance activity management.
      The aim of this paper is to present a description of a system along with data
      regarding the acceptability, satisfaction, and preliminary efficacy of a virtual
      reality (VR) environment for the promotion of positive emotions. The VR
      environment was especially designed for chronic pain patients. Results showed
      significant increases in general mood state, positive emotions, motivation, and
      self-efficacy. These preliminary findings show the potential of VR as an adjunct
      to the psychological treatment of such an important health problem as chronic
      pain.

PMID- 24892202
TI  - Mobile devices as adjunctive pain management tools.
AB  - Approximately 108 million people in North America and Europe suffer from chronic
      pain. Virtual reality (VR) is a promising method for pain management in a
      clinical setting due to the distracting properties of an immersive virtual
      environment. In this study, we demonstrated the potential use of mobile phones as
      a means of delivering an easily accessible, immersive experience. Thirty-one
      patients tested VR pain distraction. Objective measurements of heart rate
      correlated to decreased anxiety, while, subjectively, patients also reported
      reduced levels of discomfort. The positive results of this study indicate that
      mobile phones can provide an immersive experience sufficient to deliver pain
      management distraction. Because mobile devices are widely available, the
      potential for developing pain management programs that are accessible has become
      a realistic possibility.

PMID- 24892203
TI  - Virtual reality and musculoskeletal pain: manipulating sensory cues to improve
      motor performance during walking.
AB  - Musculoskeletal pain (MSP) is the most expensive nonmalignant health problem and
      the most common reason for activity limitation. Treatment approaches to improve
      movement without aggravating pain are urgently needed. Virtual reality (VR) can
      decrease acute pain, as well as influence movement speed. It is not clear whether
      VR can improve movement speed in individuals with MSP without aggravating pain.
      This study investigated the extent to which different audio and optic flow cues
      in a VR environment influenced walking speed in people with and without MSP. A
      total of 36 subjects participated, 19 with MSP and 17 controls. All walked on a
      motorized self-paced treadmill interfaced with a three-dimensional virtual
      walkway. The audio tempo was scaled (75%, 100%, and 125%) from baseline cadence,
      and optic flow was either absent, or scaled to 50% or 100% of preferred walking
      speed. Gait speed was measured during each condition, and pain was measured
      before and after the experiment. Repeated measures analysis of variance showed
      that audio tempo above baseline cadence significantly increased walking speed in
      both groups, F(3, 99)=10.41, p<0.001. Walking speed increases of more than 25%
      occurred in both groups in the 125% audio tempo condition, without any
      significant increase in pain. There was also a trend toward increased walking
      speeds with the use of optic flow, but the results in this study did not achieve
      significance at the p<0.05 level, F(2, 66)=2.01, p=0.14. Further research is
      needed to establish the generalizability of increasing movement speed across
      different physical performance tasks in VR.

PMID- 24892205
TI  - Pain management in virtual reality: a comprehensive research chart.

PMID- 24892204
TI  - Feasibility of articulated arm mounted Oculus Rift Virtual Reality goggles for
      adjunctive pain control during occupational therapy in pediatric burn patients.
AB  - For daily burn wound care and therapeutic physical therapy skin stretching
      procedures, powerful pain medications alone are often inadequate. This
      feasibility study provides the first evidence that entering an immersive virtual
      environment using very inexpensive (~$400) wide field of view Oculus Rift Virtual
      Reality (VR) goggles can elicit a strong illusion of presence and reduce pain
      during VR. The patient was an 11-year-old male with severe electrical and flash
      burns on his head, shoulders, arms, and feet (36 percent total body surface area
      (TBSA), 27 percent TBSA were third-degree burns). He spent one 20-minute
      occupational therapy session with no VR, one with VR on day 2, and a final
      session with no VR on day 3. His rating of pain intensity during therapy dropped
      from severely painful during no VR to moderately painful during VR. Pain
      unpleasantness dropped from moderately unpleasant during no VR to mildly
      unpleasant during VR. He reported going "completely inside the computer generated
      world", and had more fun during VR. Results are consistent with a growing
      literature showing reductions in pain during VR. Although case studies are
      scientifically inconclusive by nature, these preliminary results suggest that the
      Oculus Rift VR goggles merit more attention as a potential treatment for acute
      procedural pain of burn patients. Availability of inexpensive but highly
      immersive VR goggles would significantly improve cost effectiveness and increase
      dissemination of VR pain distraction, making VR available to many more patients,
      potentially even at home, for pain control as well as a wide range of other VR
      therapy applications. This is the first clinical data on PubMed to show the use
      of Oculus Rift for any medical application.

PMID- 24892206
TI  - Future directions: advances and implications of virtual environments designed for
      pain management.
AB  - Pain symptoms have been addressed with a variety of therapeutic measures in the
      past, but as we look to the future, we begin encountering new options for patient
      care and individual health and well-being. Recent studies indicate that computer
      generated graphic environments--virtual reality (VR)--can offer effective
      cognitive distractions for individuals suffering from pain arising from a variety
      of physical and psychological illnesses. Studies also indicate the effectiveness
      of VR for both chronic and acute pain conditions. Future possibilities for VR to
      address pain-related concerns include such diverse groups as military personnel,
      space exploration teams, the general labor force, and our ever increasing elderly
      population. VR also shows promise to help in such areas as drug abuse, at-home
      treatments, and athletic injuries.

PMID- 24892210
TI  - HOI versus HOIO selectivity of a molten-type AgI electrode.
AB  - AgI electrode is often applied not only to determine iodine concentration but
      also to follow oscillations in the weakly acidic medium of the Bray-Liebhafsky
      and Briggs-Rauscher reactions where it partly follows the hypoiodous acid (HOI)
      concentration. It is known that HOI attacks its matrix in the corrosion reaction:
      AgI + HOI + H(+) ? Ag(+) + I2 + H2O and the AgI electrode measures the silver ion
      concentration produced in that reaction. The signal of the electrode can be the
      basis of sensitive and selective HOI concentration measurements only supposing
      that an analogous corrosive reaction between AgI and iodous acid (HOIO) can be
      neglected. To prove that assumption, the authors calibrated a molten-type AgI
      electrode for I(-), Ag(+), HOI, and HOIO in 1 M sulfuric acid and measured the
      electrode potential in the disproportionation of HOIO, which is relatively slow
      in that medium. Measured and simulated electrode potential versus time diagrams
      showed good agreement, assuming that the electrode potential is determined by the
      HOI concentration exclusively and the contribution of HOIO is negligible. An
      independent and more direct experiment was also performed giving the same result.
      HOIO was produced with a new improved recipe. CONCLUSION: an AgI electrode can be
      applied to measure the HOI concentration selectively above the so-called
      solubility limit potential.

PMID- 24892211
TI  - Immunogen design for HIV-1 and influenza.
AB  - Vaccines provide the most cost effective defense against pathogens. Although
      vaccines have been designed for a number of viral diseases, a vaccine against HIV
      1 still remains elusive. In contrast, while there are excellent influenza
      vaccines, these need to be changed every few years because of antigenic drift and
      shift. The recent discovery of a large number of broadly neutralizing antibodies
      (bNAbs) and structural characterization of the conserved epitopes targeted by
      them presents an opportunity for structure based HIV-1 and influenza A vaccine
      design. We discuss strategies to design immunogens either targeting a particular
      antigenic region or focusing on native structure stabilization. This article is
      part of a Special Issue entitled: Recent advances in molecular engineering of
      antibody.

PMID- 24892212
TI  - Thermodynamics of engineered gold binding peptides: establishing the structure
      activity relationships.
AB  - Adsorption behavior of a gold binding peptide was experimentally studied to
      achieve kinetics and thermodynamics parameters toward understanding of the
      binding of an engineered peptide onto a solid metal surface. The gold-binding
      peptide, GBP1, was originally selected using a cell surface display library and
      contains 14 amino acid residues. In this work, single- and three-repeats of GBP1
      were used to assess the effects of two parameters: molecular architecture versus
      secondary structure on adsorption on to gold substrate. The adsorption
      measurements were carried out using surface plasmon resonance (SPR) spectroscopy
      at temperatures ranging from 10 to 55  degrees C. At all temperatures, two
      different regimes of peptide adsorption were observed, which, based on the model,
      correspond to two sets of thermodynamics values. The values of enthalpy,
      DeltaH(ads), and entropy, DeltaS(ads), in these two regimes were determined using
      the van't Hoff approach and Gibbs-Helmholtz relationship. In general, the values
      of enthalpy for both peptides are negative indicating GBP1 binding to gold is an
      exothermic phenomenon and that the binding of three repeat gold binding peptide
      (3l-GBP1) is almost 5 times tighter than that for the single repeat (l-GBP1).
      More intriguing result is that the entropy of adsorption for the 3l-GBP1 is
      negative (-43.4 +/- 8.5 cal/(mol K)), while that for the l-GBP1 is positive
      (10.90 +/- 1.3 cal/(mol K)). Among a number of factors that synergistically
      contribute to the decrease of entropy, long-range ordered self-assembly of the 3l
      GBP1 on gold surface is the most effective, probably through both peptide-solid
      and peptide-peptide intermolecular interactions. Additional adsorption
      experiments were conducted in the presence of 2,2,2-trifluoroethanol (TFE) to
      determine how the conformational structures of the biomolecules responded to the
      environmental perturbation. We found that the peptides differ in their
      conformational responses to the change in solution conditions; while l-GBP does
      not fold in the presence of TFE, 3l-GBP1 adopted two types of secondary structure
      (beta-strand, alpha-helix) and that peptide's binding to the solid is enhanced by
      the presence of low percentages of TFE solvent. Not only do these kinetics and
      thermodynamics results provide adsorption behavior and binding of genetically
      engineered peptides for inorganics (GEPI), but they could also provide
      considerable insights into fundamental understanding peptide molecular
      recognition and their selective specificity for the solids. Moreover,
      comprehensive work described herein suggests that multiple repeat forms of the
      solid binding peptides possess a conformational component that can be exploited
      to further tailor affinity and binding of a given sequence to a solid material
      followed by ordered assembly as a convenient tool in future practical
      applications.

PMID- 24892209
TI  - Protein-protein interactions and genetic diseases: The interactome.
AB  - Protein-protein interactions mediate essentially all biological processes.
      Despite the quality of these data being widely questioned a decade ago, the
      reproducibility of large-scale protein interaction data is now much improved and
      there is little question that the latest screens are of high quality. Moreover,
      common data standards and coordinated curation practices between the databases
      that collect the interactions have made these valuable data available to a wide
      group of researchers. Here, I will review how protein-protein interactions are
      measured, collected and quality controlled. I discuss how the architecture of
      molecular protein networks has informed disease biology, and how these data are
      now being computationally integrated with the newest genomic technologies, in
      particular genome-wide association studies and exome-sequencing projects, to
      improve our understanding of molecular processes perturbed by genetics in human
      diseases. This article is part of a Special Issue entitled: From Genome to
      Function.

PMID- 24892213
TI  - A new understanding of the relationship between sugars, dental caries and
      fluoride use: implications for limits on sugars consumption.
AB  - OBJECTIVE: To examine the quantitative relationship between sugar intake and the
      progressive development of dental caries. DESIGN: A critical in-depth review of
      international studies was conducted. Methods included reassessing relevant
      studies from the most recent systematic review on the relationship between levels
      of sugars and dental caries. Reanalysis of dose-response relationships between
      dietary sugars and caries incidence in teeth with different levels of caries
      susceptibility in children was done using data from Japanese studies conducted by
      Takeuchi and co-workers. SETTING: Global, with emphasis on marked differences in
      both national sugar intake and fluoride use and preferably where one factor such
      as sugar intake changed progressively without changes in other factors over a
      decade or more. SUBJECTS: Children aged 6 years or more and adults. RESULTS:
      Caries occurred in both resistant and susceptible teeth of children when sugar
      intakes were only 2-3 % of energy intake, provided that the teeth had been
      exposed to sugars for >3 years. Despite increased enamel resistance after tooth
      eruption, there was a progressive linear increase in caries throughout life,
      explaining the higher rates of caries in adults than in children. Fluoride
      affects progression of caries development but there still is a pandemic
      prevalence of caries in populations worldwide. CONCLUSIONS: Previous analyses
      based on children have misled public health analyses on sugars. The
      recommendation that sugar intakes should be <=10 % of energy intake is no longer
      acceptable. The much greater adult burden of dental caries highlights the need
      for very low sugar intakes throughout life, e.g. 2-3 % of energy intake, whether
      or not fluoride intake is optimum.

PMID- 24892214
TI  - Retention of polyphenolic species in spray-dried blackberry extract using
      mannitol as a thermoprotectant.
AB  - The purpose of these studies was to determine if a Buchi Mini Spray Dryer B-290
      (Buchi Corporation, New Castle, DE, USA) could be used to prepare blackberry
      extract powders containing mannitol as a thermoprotectant without extensively
      degrading anthocyanins and polyphenols in the resulting powders. Three blackberry
      puree extract samples were each prepared by sonication of puree in 30/70%
      ethanol/water containing 0.003% HCl. Blackberry puree extract sample 1 (S1)
      contained no mannitol, while blackberry puree extract sample 2 (S2) contained
      3.0:1 (w/w) mannitol:berry extract, and blackberry puree extract sample 3 (S3)
      contained 6.3:1 (w/w) mannitol:berry extract. The levels of anthocyanins and
      polyphenols in reconstituted spray-dried powders produced from S1-S3 were
      compared to solutions of S1-S3 that were held at 4 degrees C as controls. All
      extract samples could be spray-dried using the Buchi Mini Spray Dryer B-290. S1,
      with no mannitol, showed a 30.8% decrease in anthocyanins and a 24.1% decrease in
      polyphenols following spray-drying. However, S2 had a reduction in anthocyanins
      of only 13.8%, while polyphenols were reduced by only 6.1%. S3, with a ratio of
      mannitol to berry extract of 6.3:1, exhibited a 12.5% decrease in anthocyanins
      while the decrease in polyphenols after spray-drying was not statistically
      significant (P=.16). Collectively, these data indicate that a Buchi Mini Spray
      Dryer B-290 is a suitable platform for producing stable berry extract powders,
      and that mannitol is a suitable thermoprotectant that facilitates retention of
      thermosensitive polyphenolic species in berry extracts during spray-drying.

PMID- 24892216
TI  - Multifunctional disulfide-based cationic dextran conjugates for intravenous gene
      delivery targeting ovarian cancer cells.
AB  - A folate-decorated, disulfide-based cationic dextran conjugate having dextran as
      the main chain and disulfide-linked 1,4-bis(3-aminopropyl)piperazine (BAP)
      residues as the grafts was designed and successfully prepared as a
      multifunctional gene delivery vector for targeted gene delivery to ovarian cancer
      SKOV-3 cells in vitro and in vivo. Initially, a new bioreducible cationic
      polyamide (denoted as pSSBAP) was prepared by polycondensation reaction of bis(p
      nitrophenyl)-3,3'-dithiodipropanoate, a disulfide-containing monomer, and BAP. It
      was found that the pSSBAP was highly efficient for in vitro gene delivery against
      MCF-7 and SKOV-3 cell lines. Subsequently, two cationic dextran conjugates with
      different amounts of BAP residues (denoted as Dex-SSBAP6 and Dex-SSBAP30,
      respectively) were synthesized by coupling BAP to disulfide-linked carboxylated
      dextran or coupling pSSBAP-oligomer to p-nitrophenyl carbonated dextran. Both two
      conjugates were able to bind DNA to form nanosized polyplexes with an improved
      colloidal stability in physiological conditions. The polyplexes, however, were
      rapidly dissociated to liberate DNA in a reducing environment. In vitro
      transfection experiments revealed that the polyplexes of Dex-SSBAP30 efficiently
      transfected SKOV-3 cells, yielding transfection efficiency that is comparable to
      that of linear polyethylenimine or lipofectamine 2000. AlamarBlue assay showed
      that the conjugates had low cytotoxicity in vitro at a high concentration of 100
      mg/L. Further, Dex-SSBAP30 has primary amine side groups and thus allows for
      folate (FA) conjugation, yielding FA-coupled Dex-SSBAP30 (Dex-SSBAP30-FA). It was
      found that Dex-SSBAP30-FA was efficient for targeted gene delivery to SKOV-3
      tumor xenografted in a nude mouse model by intravenous injection, inducing a
      higher level of gene expression in the tumor as compared to Dex-SSBAP30 lacking
      FA and comparable gene expression to linear polyethylenimine as one of the most
      efficient polymeric vectors for intravenous gene delivery in vivo. Disulfide
      based cationic dextran system thus has a high potential for intravenous gene
      delivery toward cancer gene therapy. 

PMID- 24892217
TI  - Outcomes following primary percutaneous coronary intervention for unprotected
      left main-related ST-segment elevation myocardial infarction.
AB  - INTRODUCTION: Unprotected left main (ULM) related ST-segment elevation myocardial
      infarction (STEMI) is a severe event, often leading to circulatory failure and/or
      sudden cardiac death. Although high-risk ULM thrombosis populations treated by
      primary percutaneous coronary intervention (PPCI) have been previously described,
      very little is known regarding the outcomes following PPCI for ULM-related STEMI
      in a hospital without on-site surgical back-up. METHODS: A retrospective cohort
      analysis was performed on all consecutive patients who underwent PPCI for ULM
      related STEMI in a single center. The primary end-point was to assess in-hospital
      mortality in the overall population and according to the presence/absence of
      cardiogenic shock at admission. RESULTS: Between October 2006 and December 2012,
      1094 patients underwent PPCI for STEMI. PPCI for ULM-related STEMI was performed
      in 34 (3.1%) patients. Among these, 22 (64.7%) were in cardiogenic shock at
      admission. Baseline mean ejection fraction was lower (P = 0.008), whereas the
      prevalence of patients with pre-procedural cardiac arrest and Killip Class III-IV
      was significantly higher in the cardiogenic shock (P = 0.05 and P < 0.001,
      respectively) compared with non-cardiogenic shock group. Furthermore, patients
      with cardiogenic shock had a higher prevalence of pre-procedural thrombolysis in
      myocardial infarction flow 0-1 (P = 0.05) and associated other vessel chronic
      total occlusion (P = 0.05) compared with non-cardiogenic shock group. Procedural
      success rate was lower in the cardiogenic shock compared with non-cardiogenic
      shock group (77.3 vs. 100%, P = 0.09), whereas in-hospital mortality rate was
      significantly higher in the cardiogenic shock compared with non-cardiogenic shock
      group (36.4 vs. 0%, P = 0.02). No deaths were reported among survivors of the
      acute phase at mid-term follow-up, whereas target lesion revascularization rate
      was 7.6%. CONCLUSIONS: PPCI for ULM-related STEMI in a hospital without on-site
      surgical back-up was technically feasible in most of the cases. Although the
      procedural success and in-hospital mortality rates were influenced by cardiogenic
      shock at admission, an excellent mid-term outcome among patients who survived the
      hospitalization was reported independently by the severity of clinical
      presentation.

PMID- 24892215
TI  - The PTEN/NRF2 axis promotes human carcinogenesis.
AB  - AIMS: A recent study conducted in mice reported that liver-specific knockout of
      tumor suppressor Pten augments nuclear factor (erythroid-derived 2)-like 2 (NRF2)
      transcriptional activity. Here, we further investigated how phosphatase and
      tensin homolog deleted on chromosome 10 (PTEN) controls NRF2 and the relevance of
      this pathway in human carcin ogenesis. RESULTS: Drug and genetic targeting to
      PTEN and phosphoproteomics approaches indicated that PTEN leads to glycogen
      synthase kinase-3 (GSK-3)-mediated phosphorylation of NRF2 at residues Ser(335)
      and Ser(338) and subsequent beta-transducin repeat containing protein (beta-TrCP)
      dependent but Kelch-like ECH-associated protein 1 (KEAP1)-independent
      degradation. Rescue experiments in PTEN-deficient cells and xerographs in athymic
      mice indicated that loss of PTEN leads to increased NRF2 signature which provides
      a proliferating and tumorigenic advantage. Tissue microarrays from endometrioid
      carcinomas showed that 80% of PTEN-negative tumors expressed high levels of NRF2
      or its target heme oxygenase-1 (HO-1). INNOVATION: These results uncover a new
      mechanism of oncogenic activation of NRF2 by loss of its negative regulation by
      PTEN/GSK-3/beta-TrCP that may be relevant to a large number of tumors, including
      endometrioid carcinomas. CONCLUSION: Increased activity of NRF2 due to loss of
      PTEN is instrumental in human carcinogenesis and represents a novel therapeutic
      target.

PMID- 24892218
TI  - Catalytic voltammetry of the molybdoenzyme sulfite dehydrogenase from
      Sinorhizobium meliloti.
AB  - Sulfite dehydrogenase from the soil bacterium Sinorhizobium meliloti (SorT) is a
      periplasmic, homodimeric molybdoenzyme with a molecular mass of 78 kDa. It
      differs from most other well studied sulfite oxidizing enzymes, as it bears no
      heme cofactor. SorT does not readily reduce ferrous horse heart cytochrome c
      which is the preferred electron acceptor for vertebrate sulfite oxidases. In the
      present study, ferrocene methanol (FM) (in its oxidized ferrocenium form) was
      utilized as an artificial electron acceptor for the catalytic SorT sulfite
      oxidation reaction. Cyclic voltammetry of FM was used to generate the active form
      of the mediator at the electrode surface. The FM-mediated catalytic sulfite
      oxidation by SorT was investigated by two different voltammetric methods, namely,
      (i) SorT freely diffusing in solution and (ii) SorT confined to a thin layer at
      the electrode surface by a semipermeable dialysis membrane. A single set of rate
      and equilibrium constants was used to simulate the catalytic voltammograms
      performed under different sweep rates and with various concentrations of sulfite
      and FM which provides new insights into the kinetics of the SorT catalytic
      mechanism. Further, we were able to model the role of the dialysis membrane in
      the kinetics of the overall catalytic system. 

PMID- 24892219
TI  - Moderate hypothermia treatment in adult patients with severe traumatic brain
      injury: a meta-analysis.
AB  - OBJECTIVES: To evaluate the effect of moderate hypothermia treatment (MHT) in
      severe traumatic brain injury (sTBI) compared to normothermia management.
      METHODS: PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library and
      Google scholar were searched up to December 2012. Pooled risk ratios (RRs) and
      95% confidence intervals (CIs) for the mortality and clinical neurological
      outcome of the adult patients with sTBI were collected and calculated in a fixed
      effects model or a random-effects model. Summary effect estimates were stratified
      by study design and ethnicity. Egger's regression asymmetry tests were utilized
      for detecting the publication bias. RESULTS: The overall estimates showed that
      MHT could reduce the mortality (hypothermia vs. normothermia, RR = 0.86, 95% CI =
      0.73-1.01, p = 0.06) and unfavourable clinical neurological outcomes (RR = 1.21,
      95% CI = 0.95-1.53, p = 0.12) for traumatic brain injured patients without
      statistical significance. Moreover, the further stratification sub-group analysis
      indicated that MHT presented a significant reduction (RR = 0.60, 95% CI = 0.44
      0.83, p = 0.002) of mortality compared to the normothermia management in an Asian
      population. Surprisingly, American patients treated with moderate hypothermia
      showed an increasing mortality (RR = 1.07, 95% CI = 0.83-1.39, p = 0.61).
      CONCLUSIONS: MHT may be effective in reducing death and unfavourable clinical
      neurological outcomes, but this finding is not statistically significant, except
      for decreasing the mortality in Asian patients.

PMID- 24892220
TI  - Individual and group treatment for patients with acquired brain injury in
      comprehensive rehabilitation.
AB  - PRIMARY OBJECTIVE: The aim of this study was to investigate the hypothesis that
      group rehabilitation is more effective than individual treatments and provides an
      improvement in clinical outcomes similar to that achieved by individual
      treatments alone. RESEARCH DESIGN: Two groups of patients were placed in
      different rehabilitation settings treated using the same rehabilitation approach.
      One received only individual treatments and the second group received a
      combination of both individual and group treatments. The independent variables
      were measured both pre- and post-treatment and compared between the two groups.
      METHODS AND PROCEDURES: Seventy-four patients treated with a comprehensive
      rehabilitation approach were divided into two groups: (a) individual treatment
      only and, (b) combined treatments (both individual and group). The outcome scales
      were LCF (Rancho Los Amigos Level of Cognitive Functioning), DRS (Disability
      Rating Scale) and FIMTM (Functional Independence Measure). RESULTS: The whole
      sample had obtained statistically significant improvements in all of the outcome
      scales: LCF (chi(2) = 45.26; p < 0.001), DRS (z = -3.92; p < 0.001) and FIM (z = 
      4.9; p < 0.001). The comparison between groups did not reveal any pre-treatment
      difference. Analysis of post-treatment, however, showed a greater improvement in
      the FIM scale for those in combined individual and group treatment (z = -0.2544,
      p = 0.01). CONCLUSIONS: Group rehabilitation integrated with individual
      treatments is more effective than individual treatments alone in improving
      independence measured by the FIMTM scale. Both groups had obtained statistically
      significant clinical improvements, the improvement in the FIMTM scale was
      significantly better in the combined treatment group.

PMID- 24892221
TI  - Is hydrokinesitherapy effective on gait and balance in patients with stroke? A
      clinical and baropodometric investigation.
AB  - BACKGROUND: Patients with stroke present an asymmetric posture, severe balance
      dysfunction with delayed and disrupted equilibrium reactions, exaggerated
      postural sway and abnormal gait with an increased risk of falling. The aim of
      this study is to evaluate the efficacy of hydrokinesytherapy on stance, balance
      and gait in individuals after stroke. METHODS: In this single-blinded randomized
      controlled trial, patients with stroke were divided into two groups: an
      experimental one (G1), performing hydrokinesytherapy (3 times/week) in addition
      to a conventional physical therapy (3 times/week) and a control one (G2),
      performing only a conventional physical therapy (6 times/week). All of the
      participants underwent a proper clinical and baropodometric evaluation before and
      after 8 weeks of treatment. RESULTS: The two groups presented similar clinical
      and instrumental features at enrolment (mean modified Rankin Scale of 3, and a
      disease duration of 6.3 +/- 1.4 months). After treatment, the patients undergoing
      hydrokinesytherapy showed a significantly greater improvement than those
      undergoing traditional training. CONCLUSIONS: Hydrokinesytherapy may be
      considered a promising treatment in improving gait and balance in individuals
      following stroke.

PMID- 24892222
TI  - Reliability of the timed 10-metre walk test during inpatient rehabilitation in
      ambulatory adults with traumatic brain injury.
AB  - OBJECTIVE: To determine the test-re-test reliability of the timed 10-metre walk
      test (10MWT) among adults with traumatic brain injury (TBI) enrolled in inpatient
      rehabilitation. DESIGN: Prospective reliability study using a correlational
      design. SETTING: Inpatient rehabilitation unit of a rehabilitation hospital.
      PARTICIPANTS: Twenty-three consecutive adults with acute TBI, mean age = 35.87,
      SD = 14.2 years (range = 18-64 years). This study tested 22 males and one female,
      who were 15.6 (SD = 9.1) days in inpatient rehabilitation at time of gait
      testing. METHOD: Repeated, timed 10-metre gait test within a 1-hour testing
      period with six trials at self-selected pace (SSP) and six trials at fastest pace
      (FP), recorded to the nearest 1/10 second with a hand-held stopwatch. RESULT:
      Gait speed measurements for SSP and FP were shown to have excellent test-re-test
      reliability (Intra Class Correlation coefficient = 0.964 and 0.961,
      respectively). CONCLUSIONS: These results add to the literature that the timed
      10MWT is a reliable measure of gait velocity in adults with acute TBI for both FP
      and SSP.

PMID- 24892223
TI  - Functional correlates of prospective memory in stroke.
AB  - INTRODUCTION: Prospective memory is the ability to remember actions to be
      performed later in time or when a certain event occurs. Multiple cognitive
      processes are involved in prospective memory, and the degree to which automatic
      or effortful processes are involved may differ for different types of prospective
      memory tasks. This study aimed to investigate prospective memory (dys)functioning
      in stroke patients, and to get more insight in which cognitive processes are
      involved in time- versus event-based prospective memory. METHODS: We investigated
      39 community-dwelling stroke survivors and 53 matched control participants.
      Assessment included naturalistic and experimental event- and time-based
      prospective memory tasks, as well as standard neuropsychological measures of
      (retrospective) memory, processing speed and attention/executive functioning.
      RESULTS: 41% of the stroke patients performed significantly worse than control
      participants on prospective memory tasks. Deficits in prospective memory occurred
      as frequently as impairments in retrospective memory (33%, chi(2)(1, N=39)=3.4,
      p=.066), and more often than impairments in attention/executive functioning (15%,
      chi(2)(1, N=39)=5.2, p=.022) and speed of processing (23%, chi(2)(1, N=39)=6.5,
      p=.011). Regression analyses showed that event-based ('focal') prospective memory
      is supported by retrospective memory, indicating that it is a relatively simple
      and automatic process. Time-based (non-'focal') prospective memory proved to be a
      more complex process, requiring active monitoring of the environment. Performance
      was predicted by speed of processing, attention/executive functioning and
      retrospective memory. Thirteen percent of the patients suffered from selective
      prospective memory impairment, which was associated with damage to the superior
      temporal gyrus. CONCLUSIONS: Impairment of prospective memory occurs frequently
      after stroke. Different cognitive operations are involved in distinct types of
      prospective memory. Results fit within the multi-process framework of prospective
      memory and help further specify its contents.

PMID- 24892225
TI  - Choice of cochlear implant side in a paediatric population.
AB  - OBJECTIVE: To compare the effect of right- or left-sided cochlear implantation on
      listening skills in a paediatric population. METHODS: A retrospective analysis
      was conducted on the listening skills performance data of children who were
      operated on and followed up at the Cukurova University Department of
      Otorhinolaryngology between 2007 and 2011. Sixty-three patients were included in
      the study. Patients were evaluated using the Listening Progress Profile, the
      Meaningful Auditory Integration Scale and the littlEARS test. RESULTS: The mean
      age of the children was two years (range of one to five years). Twenty-nine
      patients were male and 34 were female. Twenty-eight patients were implanted in
      the right ear and 35 in the left ear. There were no statistically significant
      differences between right and left ear implantees in terms of listening skills
      performance. CONCLUSION: This study indicates that the choice of cochlear implant
      side is not crucial for the development of listening skills.

PMID- 24892226
TI  - Quantitative nonlinear optical assessment of atherosclerosis progression in
      rabbits.
AB  - Quantification of atherosclerosis has been a challenging task owing to its
      complex pathology. In this study, we validated a quantitative approach for
      assessing atherosclerosis progression in a rabbit model using a numerical matrix,
      optical index for plaque burden, derived directly from the nonlinear optical
      microscopic images captured on the atherosclerosis-affected blood vessel. A
      positive correlation between this optical index and the severity of
      atherosclerotic lesions, represented by the age of the rabbits, was established
      based on data collected from 21 myocardial infarction-prone Watanabe heritable
      hyperlipidemic rabbits with age ranging between new-born and 27 months old. The
      same optical index also accurately identified high-risk locations for
      atherosclerotic plaque formation along the entire aorta, which was validated by
      immunohistochemical fluorescence imaging. 

PMID- 24892227
TI  - Ozone phytotoxic potential with regard to fragments of the Atlantic Semi
      deciduous Forest downwind of Sao Paulo, Brazil.
AB  - In the Metropolitan Region of Campinas (MRC), Brazil, high levels of primary
      pollutants contribute to ozone (O3) formation. However, little is known regarding
      the O3 effects in the tropics. Objectives in this study were to characterize the
      present levels of O3 pollution and to evaluate the relevance of current
      concentration-based indices for assessing the phytotoxic potential of O3. Changes
      in O3 concentrations and precursors at 5 monitoring stations within towns of MRC
      were analyzed. The daily O3 profile was typical for urban sites and showed little
      yearly variation. Given the permanently foliated forest canopy, yearly rather
      than seasonal O3 indices were thus more appropriate for estimating the effective
      ozone dose. With yearly SUM00, SUM60 and AOT40 of 156, 16 and 14 ppm h and
      confirmed by evidence of O3 injury in foliage, oxidative stress in the MRC has
      reached levels high enough to affect trees from the Atlantic Semi-deciduous
      Forest. 

PMID- 24892224
TI  - Parcellation of left parietal tool representations by functional connectivity.
AB  - Manipulating a tool according to its function requires the integration of visual,
      conceptual, and motor information, a process subserved in part by left parietal
      cortex. How these different types of information are integrated and how their
      integration is reflected in neural responses in the parietal lobule remains an
      open question. Here, participants viewed images of tools and animals during
      functional magnetic resonance imaging (fMRI). k-Means clustering over time series
      data was used to parcellate left parietal cortex into subregions based on
      functional connectivity to a whole brain network of regions involved in tool
      processing. One cluster, in the inferior parietal cortex, expressed privileged
      functional connectivity to the left ventral premotor cortex. A second cluster, in
      the vicinity of the anterior intraparietal sulcus, expressed privileged
      functional connectivity with the left medial fusiform gyrus. A third cluster in
      the superior parietal lobe expressed privileged functional connectivity with
      dorsal occipital cortex. Control analyses using Monte Carlo style permutation
      tests demonstrated that the clustering solutions were outside the range of what
      would be observed based on chance 'lumpiness' in random data, or mere anatomical
      proximity. Finally, hierarchical clustering analyses were used to formally relate
      the resulting parcellation scheme of left parietal tool representations to
      previous work that has parcellated the left parietal lobule on purely anatomical
      grounds. These findings demonstrate significant heterogeneity in the functional
      organization of manipulable object representations in left parietal cortex, and
      outline a framework that generates novel predictions about the causes of some
      forms of upper limb apraxia. 

PMID- 24892228
TI  - Detoxification and recovery capacities of Corbicula fluminea after an industrial
      metal contamination (Cd and Zn): a one-year depuration experiment.
AB  - This study aimed to assess the recovery capacity of the freshwater bivalve
      Corbicula fluminea subjected to industrial metal discharges (Cd, Zn). After a 24
      day exposure in a metal-contaminated river, bivalves were transferred and
      maintained in the laboratory for one year under metal-free conditions. Metal
      accumulation, metallothionein production and genetic expressions of genes
      involved in metal stress were studied. Results demonstrated the high persistence
      of Cd in tissues (only 73% eliminated after 365 days) whereas Zn was rapidly
      depurated. The Cd half-life was estimated around 240 days. Metallothioneins were
      strongly induced within the 28 first days of decontamination, then decreased by
      45% after 365 days. The metal exposure of bivalves led to a significant gene
      induction. After 28 days, most of the genes were no longer overexpressed,
      suggesting that the bivalves may withstand small amounts of non-essential metals
      in their tissues without showing signs of detrimental effects on the tested
      genes. 

PMID- 24892229
TI  - Nonlinear frequency compression in hearing aids: impact on speech and language
      development.
AB  - OBJECTIVES: The research questions of this study were: (1) Are children using
      nonlinear frequency compression (NLFC) in their hearing aids getting better
      access to the speech signal than children using conventional processing schemes?
      The authors hypothesized that children whose hearing aids provided wider input
      bandwidth would have more access to the speech signal, as measured by an
      adaptation of the Speech Intelligibility Index, and (2) are speech and language
      skills different for children who have been fit with the two different
      technologies; if so, in what areas? The authors hypothesized that if the children
      were getting increased access to the speech signal as a result of their NLFC
      hearing aids (question 1), it would be possible to see improved performance in
      areas of speech production, morphosyntax, and speech perception compared with the
      group with conventional processing. DESIGN: Participants included 66 children
      with hearing loss recruited as part of a larger multisite National Institutes of
      Health-funded study, Outcomes for Children with Hearing Loss, designed to explore
      the developmental outcomes of children with mild to severe hearing loss. For the
      larger study, data on communication, academic and psychosocial skills were
      gathered in an accelerated longitudinal design, with entry into the study between
      6 months and 7 years of age. Subjects in this report consisted of 3-, 4-, and 5
      year-old children recruited at the North Carolina test site. All had at least at
      least 6 months of current hearing aid usage with their NLFC or conventional
      amplification. Demographic characteristics were compared at the three age levels
      as well as audibility and speech/language outcomes; speech-perception scores were
      compared for the 5-year-old groups. RESULTS: Results indicate that the audibility
      provided did not differ between the technology options. As a result, there was no
      difference between groups on speech or language outcome measures at 4 or 5 years
      of age, and no impact on speech perception (measured at 5 years of age). The
      difference in Comprehensive Assessment of Spoken Language and mean length of
      utterance scores for the 3-year-old group favoring the group with conventional
      amplification may be a consequence of confounding factors such as increased
      incidence of prematurity in the group using NLFC. CONCLUSIONS: Children fit with
      NLFC had similar audibility, as measured by a modified Speech Intelligibility
      Index, compared with a matched group of children using conventional technology.
      In turn, there were no differences in their speech and language abilities.

PMID- 24892230
TI  - The Wistar legacy to embryonic stem cell research.

PMID- 24892231
TI  - Creating Neoliberal Citizens in Morocco: Reproductive Health, Development Policy,
      and Popular Islamic Beliefs.
AB  - Self-governance and responsibility are two traits associated with neoliberal
      citizenship in scholarly and popular discourses, but little of the literature on
      this topic focuses on North Africa. My goal, in this article, is not only to fill
      this void but also to complicate understandings of neoliberalism through an
      examination of the relationship between reproductive health care, development
      policy, and popular Islamic beliefs in Morocco. My discussion is based on
      fieldwork in Rabat, Morocco, which included observations in health clinics,
      interviews with patients and staff, and visits to patients' homes. By analyzing
      the childbearing and childrearing practices of Moroccan women who visited the
      clinics, I pose that neoliberal logic cannot be predefined or understood as a
      monolithic concept. I demonstrate that women were active in their own governance
      and accountable for their reproductive behaviors, but they did so because of
      their understandings of what Islam says about fertility and motherhood. 

PMID- 24892232
TI  - Danger and dementia: caregiver experiences and shifting social roles during a
      highly active hurricane season.
AB  - This study examined disaster preparedness and decision-making by caregivers of
      community-dwelling persons diagnosed with Alzheimer's or a related dementia
      (ADRD). Interviews were conducted with 20 caregivers in South Florida. Twelve of
      these interviews include caregiving experiences during the highly active 2004
      2005 hurricane seasons. Results indicate that persons in earlier stages of ADRD
      can, and often do, remain engaged in the disaster preparation and planning
      process. However, during the early stages, persons may also resist evacuation,
      even if the caregiver felt it was necessary. During later stages of the disease,
      caregivers reported less resistance to disaster-related decisions, however, with
      the tradeoff of less ability to assist with preparation.

PMID- 24892235
TI  - Post-trial access and the new version of the Declaration of Helsinki.

PMID- 24892233
TI  - Validation of maturity offset in a longitudinal sample of Polish girls.
AB  - This study attempted to validate an anthropometric equation for predicting age at
      peak height velocity (PHV) in 198 Polish girls followed longitudinally from 8 to
      18 years. Maturity offset (years before or after PHV) was predicted from
      chronological age, mass, stature, sitting height and estimated leg length at each
      observation; predicted age at PHV was the difference between age and maturity
      offset. Actual age at PHV for each girl was derived with Preece-Baines Model 1.
      Predicted ages at PHV increased from 8 to16 years and varied relative to time
      before and after actual age at PHV. Predicted and actual ages at PHV did not
      differ at 9 years, but predicted overestimated actual age at PHV from 10 to 16
      years. Girls of contrasting maturity status differed in predicted age at PHV from
      8 to 14 years. In conclusion, predicted age at PHV is dependent upon age at
      prediction and individual differences in actual age at PHV, which limits its
      utility as an indicator of maturity timing in general and in sport talent
      programmes. It may have limited applicability as a categorical variable (pre-,
      post-PHV) among average maturing girls during the interval of the growth spurt,
      ~11.0-13.0 years.

PMID- 24892236
TI  - Status of allele frequency and diversity of Plasmodium falciparum msp1, msp2 and
      glurp before implementation of an artemisinin-based combined therapy in
      Northwestern Colombia.
AB  - INTRODUCTION: The status of msp1, msp2 and glurp allele frequency and the
      diversity of Plasmodium falciparum in Northwestern Colombia before the
      implementation of an artemisinin-combined therapy have been explored only by a
      few authors and in a relatively small number of samples from this highly endemic
      region. OBJECTIVE: To evaluate the frequency of msp1, msp2, and glurp alleles and
      the diversity of P. falciparum in two Colombian regions before the use of an
      artemisinin-combined therapy. METHODS: This study was part of a major anti
      malarial efficacy trial designed as a random, clinically-controlled study for
      which 224 subjects were recruited. Region 2 of msp1 and msp2 (central region)
      were amplified by a nested PCR; glurp (region R2) was amplified by a semi-nested
      PCR. RESULTS: For msp1, five genotypes were observed, representing the K1, MAD20,
      and RO33 allelic families. All samples corresponded to a MAD20 150 bp allele. For
      msp2 (IC family), two alleles were detected and for glurp, eight were observed. A
      total 33 haplotypes were detected. CONCLUSIONS: Analysis of glurpcan be used to
      successfully genotype parasite populations in the new studies in Colombia aimed
      at exploring Plasmodium spp population dynamics. In addition, analysis of msp1
      and msp2 can also be of value for comparisons with past studies, but not when the
      objective is to study parasites obtained from the same patient in a reduced
      period of time; for instance, during treatment efficacy studies.

PMID- 24892237
TI  - Individual differences in personality profiles among potential living kidney
      transplant donors.
AB  - BACKGROUND: Although the psychological assessment of potential living kidney
      donors (PLKD) is part of the recommendations for action for any transplant
      coordination, there are not many studies that provide data about the importance
      of selecting donors for improving transplant outcomes. This work aims to raise
      awareness of potential kidney donors by designing methods for early detection of
      potential problems after the transplant, as well as by selecting the most
      suitable donors. METHODS: This is a study of 25 PLKD drawn from the General
      University Hospital of Alicante. Participants completed the Millon Clinical
      Multiaxial Inventory (MCMI-III) for the study of personality characteristics.
      RESULTS: Women scored higher than men in the compulsive personality scale, and
      individuals with a genetic link with the recipient scored higher on depressive
      and dependent scales than did those with other relationships (emotional or
      altruistic). CONCLUSIONS: Women showed a pattern of significantly more compulsive
      personality traits (cautious, controlled, perfectionist) within a non
      pathological style. Among the PLKD, there were significantly more women, which is
      contrary to what typically happens with donations from cadavers. Genetically
      related subjects scored higher on depression than did those that were emotionally
      related. The personality assessment of candidates for PLKD can help with
      developing a post-transplant follow-up regimen for an improved quality of life.

PMID- 24892238
TI  - Ocular trauma from land mines among soldiers treated at a University Hospital in
      Medellin, Colombia.
AB  - INTRODUCTION: Currently ocular combat injuries are complex and associated with
      poor visual outcomes. Our objective is to characterize the military population
      that suffer land mine combat ocular trauma in Colombia and identify the type of
      wound, treatment and visual outcomes. METHODS: Retrospectively review of medical
      history of soldiers evaluated in Pablo Tobon Uribe Hospital, whom had land mine
      trauma during January of 2004 and December 2012. RESULTS: 635 soldiers had land
      mine trauma, 153 of them had ocular trauma (226 eyes). Open ocular trauma was
      observed in 29.6%. The Ocular Trauma Score was calculated in 183 eyes, the
      initial visual acuity was not possible to be reported in the rest of them; the
      45% of the eyes were classified in category 3. Three patients had no light
      perception in both eyes. 97.3% of the eyes received medical treatment and 49.1%
      had surgery also. Primary evisceration was made in 5.8% and enucleation in 1.8%.
      Intraocular foreign body was observed by ultrasonography in 11.1% and in 5.8% by
      orbital tomography. Eleven patients were legally blind at discharge. CONCLUSIONS:
      The ocular trauma related to a land mine is highly destructive at an ocular
      level. The treatments associated with better visual outcomes are primary closure
      of globe and systemic antibiotics; although the characteristics of the wound
      itself are the main prognostic factor. The Ocular trauma score is a useful tool
      for determining visual outcome in combat ocular trauma.

PMID- 24892239
TI  - Prevalence of poor self-rated health and associated risk factors among older
      adults in Cali, Colombia.
AB  - INTRODUCTION: Self-rated health (SRH) has beeen considered an important marker of
      quality of life and an independent predictor of mortality in older adults.
      OBJECTIVE: To determine the prevalence of poor SRH and identify risk factors
      associated with poor SRH among older adults residing in the Commune 18 of the
      city of Cali, Colombia, in 2009. METHODS: A population-based cross-sectional
      study with a single-stage cluster sampling design. Sample included 314 persons
      aged 60 and older. The dependent variable, SRH was dichotomized into good
      (excellent, very good, good) and poor (fair, poor). Independent variables were
      sociodemographic, biological, mental, functional and geriatric syndromes.
      Logistic regression was used for multivariate statistical modeling. RESULTS:
      Overall, 40.1% reported poor SRH (women 42.9%, men 35.0%). Factors independently
      associated with poor SRH were diabetes mellitus, depression, fear of falling and
      frailty syndrome (frail and pre-frail vs. non-frail). Widowed men reported poorer
      health than married men while other marital status (single/separated/divorced)
      was associated with better self-rated health in women. CONCLUSION: Potential
      modifiable factors such as depression and frailty syndrome are important
      determinants for poor SRH in Colombian older adults.

PMID- 24892240
TI  - Toxoplasmosis of the spinal cord in an immunocompromised patient: case report and
      review of the literature.
AB  - We, herein, describe an HIV-positive patient with toxoplasmosis of the spinal
      cord. We also carried out a comprehensive literature review of this topic, with
      emphasis on the diagnostic tools and therapeutic approach. 

PMID- 24892242
TI  - Lack of transparency in clinical trials: a call for action.

PMID- 24892241
TI  - Anemia and transfusion of red blood cells.
AB  - The red cells transfusion is a mainstay in the treatment of anemic patients.
      These blood transfusions are not without risks. The risk-benefit profile for red
      cell transfusions to treat anaemia is uncertain, but they may contribute to
      adverse patient outcomes in some situations. The ability of a patient to tolerate
      anaemia depends on their clinical condition and the presence of any significant
      co-morbidity; maintenance of circulating volume is of paramount importance. There
      is no universal transfusion trigger. Advances in the development and validation
      of physiological, accessible, practical and reliable markers to guide therapy are
      expected. To improve patients' outcomes, further study is required to more fully
      explore the risk of anemia, optimal hemoglobin level, and the risk and efficacy
      of RBC transfusion. Future clinical investigations with high priority should
      determine the efficacy of transfusion in those classified as uncertain scenarios.
      In the absence of data, it is prudent that transfusion is administered with
      caution in these clinical scenarios. 

PMID- 24892244
TI  - Responding to: Parallel analysis and MBI-HSS.

PMID- 24892243
TI  - Parallel analysis and MBI-HSS: How many factors?

PMID- 24892245
TI  - Rapid enumeration of phage in monodisperse emulsions.
AB  - Phage-based detection assays have been developed for the detection of viable
      bacteria for applications in clinical diagnosis, monitoring of water quality, and
      food safety. The majority of these assays deliver a positive readout in the form
      of newly generated progeny phages by the bacterial host of interest. Progeny
      phages are often visualized as plaques, or holes, in a lawn of bacteria on an
      agar-filled Petri dish; however, this rate-limiting step requires up to 12 h of
      incubation time. We have previously described an amplification of bacteriophages
      M13 inside droplets of media suspended in perfluorinated oil; a single phage M13
      in a droplet yields 10(7) copies in 3-4 h. Here, we describe that encapsulation
      of reporter phages, both lytic T4-LacZ and nonlytic M13, in monodisperse droplets
      can also be used for rapid enumeration of phage. Compartmentalization in droplets
      accelerated the development of the signal from the reporter enzyme; counting of
      "positive" droplets yields accurate enumeration of phage particles ranging from
      10(2) to 10(6) pfu/mL. For enumeration of T4-LacZ phage, the fluorescent signal
      appeared in as little as 90 min. Unlike bulk assays, quantification in emulsion
      is robust and insensitive to fluctuations in environmental conditions (e.g.,
      temperature). Power-free emulsification using gravity-driven flow in the absence
      of syringe pumps and portable fluorescence imaging solutions makes this
      technology promising for use at the point of care in low-resource environments.
      This droplet-based phage enumeration method could accelerate and simplify point
      of-care detection of the pathogens for which reporter bacteriophages have been
      developed. 

PMID- 24892246
TI  - Unusual presentation of follicular carcinoma thyroid with special emphasis on
      their management.
AB  - INTRODUCTION: Follicular carcinoma of thyroid usually behaves in an indolent
      manner with low metastatic potential. Distant metastases as initial presentation
      is rare in follicular carcinoma; especially in young patients. PRESENTATION OF
      CASE: We report the clinical, pathological features and the management of three
      different cases of follicular carcinoma of the thyroid with unusual presentations
      at the time of diagnosis. First case presented as thyroid abscess, second case
      with a large skull swelling in a pre-exiting goiter and the third case with a
      swelling in the sternum. DISCUSSION: Follicular carcinoma of thyroid is the
      second category of well-differentiated thyroid cancer that constitutes about 10%
      of all thyroid malignancies. Blood borne metastasis is common with spread to
      lung, bone and other solid organs. In less than 10% cases of follicular
      carcinoma, there is evidence of lymphatic involvement. The patients'
      presentations above are highly unusual. CONCLUSION: Recognizing these cases has a
      significant impact on clinical decision-making and prognosis of the patients.
      Treatment in these patients should be individualized and an alternative
      therapeutic approach should be considered.

PMID- 24892247
TI  - A rare variant of inguinal hernia: Cryptorchid testis at the age of 50 years.
      Etiopathogenicity, prognosis and management.
AB  - INTRODUCTION: Cryptorchidism is characterized by the extra-scrotal position of
      the testis. The surgical community has little to no knowledge of cryptorchid
      testis in adults apart from of pediatric surgeons. Therefore, we sought to
      describe this unusual cause of inguinal hernia. PRESENTATION OF CASE: A 50-year
      old man was referred with a inguinal hernia. Diagnosis of cryptorchidism was made
      during surgery, as the patient underwent an operation for repair of his left
      inguinal hernia. The testicle was non-viable and a left testicle was resected.
      Histopathology report confirmed a atrophic testis without testicular germ cell
      tumor (TGCT). DISCUSSION: This is an extremely rare case of cryptorchidism
      revealed in an adult. The patient remained asymptomatic for 50 years. Most
      studies have concluded that there is a direct correlation between how long the
      testis was subjected to a cryptorchid position and TGCT incidence. The
      recommended age of surgical correction is before the age of 2 years. In our case,
      we did not find correlation between the time of surgery and risk of TGCT.
      Histopathology report confirmed the presence of leydig cells, seminiferous tubule
      and Sertoli cells without TGCT. Very little is known about link between
      cryptorchidism and TGCT. The correct diagnosis of inguinal hernia is usually made
      during an inguinal hernia repair. CONCLUSION: The surgeon must always be alert to
      the possibility of cryptorchid testis during a surgical exploration of an
      inguinal hernia. In suspected cases, laparoscopy ultrasonographic, CT scan and
      laparoscopy evaluation may be helpful in diagnosing of this atypical inguinal
      hernia before surgery.

PMID- 24892248
TI  - A rare case of extensive diffuse nonpigmented villonodular synovitis as a cause
      of total knee arthroplasty failure.
AB  - INTRODUCTION: Nonpigmented villonodular synovitis (non-PVNS) is a benign
      proliferative disease involving the synovium. It is a rare condition that is
      little recognized. Non-PVNS has been reported as a cause of total knee
      replacement failure. PRESENTATION OF CASE: We report a case of extensive diffuse
      non-PVNS in a patient with tibial component loosening after total knee
      replacement and review the related literature. DISCUSSION: It is reported that
      pigmented villonodular synovitis (PVNS) occurs less frequently than non-PVNS
      after knee replacement. However, there are many more case reports of PVNS than
      non-PVNS after knee arthroplasty in the English-language literature. CONCLUSION:
      Previously, there were no reported cases of extensive diffuse non-PVNS after
      total knee arthroplasty (TKA). This case study highlights an unusual case of non
      PVNS as a cause of TKA failure. We propose that non-PVNS should be considered as
      a differential diagnosis in patients after TKA who present with recurrent pain
      and effusion/hemarthrosis of the knee, and that it is one of the causes of
      implant loosening after TKA.

PMID- 24892249
TI  - Response to publications by Heyward W et al. and Kuan R et al.: Clinical and cost
      effectiveness analyses, respectively, of hepatitis B vaccination-HeplisavTM
      compared with Engerix-B((r)) vaccine in adults.

PMID- 24892250
TI  - Robust manufacturing and comprehensive characterization of recombinant hepatitis
      E virus-like particles in Hecolin((r)).
AB  - The hepatitis E virus (HEV) vaccine, Hecolin((r)), was licensed in China for the
      prevention of HEV infection and HEV-related diseases with demonstrated safety and
      efficacy [1,2]. The vaccine is composed of a truncated HEV capsid protein, p239,
      as the sole antigen encoded by open reading frame 2 and produced using
      Escherichia coli platform. The production of this virus-like particle (VLP) form
      of the antigen was successfully scaled up 50-fold from a bench scale to a
      manufacturing scale. Product consistency was demonstrated using a combination of
      biophysical, biochemical and immunochemical methods, which revealed comparable
      antigen characteristics among different batches. Particle size of the nanometer
      scale particulate antigen and presence of key epitopes on the particle surface
      are two prerequisites for an efficacious VLP-based vaccine. The particle size was
      monitored by several different methods, which showed diameters between 20 and
      30nm for the p239 particles. The thermal stability and aggregation propensity of
      the antigen were assessed using differential scanning calorimetry and cloud point
      assay under heat stress conditions. Key epitopes on the particulate antigen were
      analyzed using a panel of murine anti-HEV monoclonal antibodies (mAbs). The
      immuno reactivity to the mAbs among the different antigen lots was highly
      consistent when analyzed quantitatively using a surface plasmon resonance
      technique. Using a sandwich ELISA to probe the integrity of two different
      epitopes in the antigen, the specific antigenicity of multiple batches was
      assessed to demonstrate consistency in these critical product attributes.
      Overall, our findings showed that the antigen production process is robust and
      scalable during the manufacturing of Hecolin((r)). 

PMID- 24892253
TI  - Letter from the editor.

PMID- 24892252
TI  - Aluminium in allergen-specific subcutaneous immunotherapy--a German perspective.
AB  - We are living in an "aluminium age" with increasing bioavailability of the metal
      for approximately 125 years, contributing significantly to the aluminium body
      burden of humans. Over the course of life, aluminium accumulates and is stored
      predominantly in the lungs, bones, liver, kidneys and brain. The toxicity of
      aluminium in humans is briefly summarised, highlighting links and possible causal
      relationships between a high aluminium body burden and a number of neurological
      disorders and disease states. Aluminium salts have been used as depot-adjuvants
      successfully in essential prophylactic vaccinations for almost 100 years, with a
      convincing positive benefit-risk assessment which remains unchanged. However,
      allergen-specific immunotherapy commonly consists of administering a long-course
      programme of subcutaneous injections using preparations of relevant allergens.
      Regulatory authorities currently set aluminium limits for vaccines per dose,
      rather than per treatment course. Unlike prophylactic vaccinations, numerous
      injections with higher proportions of aluminium-adjuvant per injection are
      applied in subcutaneous immunotherapy (SCIT) and will significantly contribute to
      a higher cumulative life dose of aluminium. While the human body may cope
      robustly with a daily aluminium overload from the environment, regulatory
      cumulative threshold values in immunotherapy need further addressing. Based on
      the current literature, predisposing an individual to an unusually high level of
      aluminium, such as through subcutaneous immunotherapy, has the potential to form
      focal accumulations in the body with the propensity to exert forms of toxicity.
      Particularly in relation to longer-term health effects, the safety of aluminium
      adjuvants in immunotherapy remains unchallenged by health authorities - evoking
      the need for more consideration, guidance, and transparency on what is known and
      not known about its safety in long-course therapy and what measures can be taken
      to prevent or minimise its risks. The possibility of providing an effective means
      of measuring aluminium accumulation in patients undergoing long-term SCIT
      treatment as well as reducing their aluminium body burden is discussed. 

PMID- 24892251
TI  - Physiologic and metabolic safety of butyrylcholinesterase gene therapy in mice.
AB  - In continuing efforts to develop gene transfer of human butyrylcholinesterase
      (BChE) as therapy for cocaine addiction, we conducted wide-ranging studies of
      physiological and metabolic safety. For that purpose, mice were given injections
      of adeno-associated virus (AAV) vector or helper-dependent adenoviral (hdAD)
      vector encoding human or mouse BChE mutated for optimal cocaine hydrolysis. Age
      matched controls received saline or AAV-luciferase control vector. At times when
      transduced BChE was abundant, physiologic and metabolic parameters in conscious
      animals were evaluated by non-invasive Echo-MRI and an automated "Comprehensive
      Laboratory Animal Monitoring System" (CLAMS). Despite high vector doses (up to
      10(13) particles per mouse) and high levels of transgene protein in the plasma
      (~1500-fold above baseline), the CLAMS apparatus revealed no adverse physiologic
      or metabolic effects. Likewise, body composition determined by Echo-MRI, and
      glucose tolerance remained normal. A CLAMS study of vector-treated mice given 40
      mg/kg cocaine showed none of the physiologic and metabolic fluctuations exhibited
      in controls. We conclude that neither the tested vectors nor great excesses of
      circulating BChE affect general physiology directly, while they protect mice from
      disturbance by cocaine. Hence, viral gene transfer of BChE appears benign and
      worth exploring as a therapy for cocaine abuse and possibly other disorders as
      well.

PMID- 24892254
TI  - Programmed death-1 inhibition in renal cell carcinoma: clinical insights and
      future directions.
AB  - The treatment of metastatic renal cell carcinoma (mRCC) has evolved markedly over
      the past decade, broaden- ing beyond immune-based strategies (eg, interleukin-2
      and interferon-alpha) to include targeted agents (eg, sunitinib [Sutent, Pfizer]
      and sorafenib [Nexavar, Bayer]). Recently, there has been a renewed interest in
      immune-based strategies, with clinical trials underway to assess vaccines and
      other immunomodulatory agents. Of particular interest are agents that inhibit the
      interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1)
      at the T-cell/antigen-presenting cell interface. This interaction produces T-cell
      anergy and therefore stifles the antitumor immune response. Monoclonal antibodies
      to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and
      BMS-936559) are in various stages of clinical development. The clinical
      trajectory of these agents is discussed herein, with specific attention to the
      potential placement of PD-1/ PD-L1 inhibition in the crowded therapeutic
      landscape of mRCC.

PMID- 24892255
TI  - How often do hematologists consider celiac disease in iron-deficiency anemia?
      Results of a national survey.
AB  - BACKGROUND: Celiac disease (CD) is underdiagnosed, and iron-deficiency anemia
      (IDA) is a common presentation of CD. No guidelines exist in the literature for
      screening for CD among those with IDA in the United States. We surveyed
      hematologists to deter- mine rates of CD screening in patients with IDA. METHODS:
      A survey was e-mailed to members of the American Society of Hematology. RESULTS:
      There were 385 complete responses from 4551 e-mails. Most respondents were
      practicing clinicians (74%), clinical researchers (10%), or laboratory
      researchers (6%). Specialists in benign hematology accounted for 45% of
      respondents, oncologists accounted for 33%, and specialists in malignant
      hematology accounted for 22%. The most common practice types were university
      affiliated hospital (43%), private clinic (29%), community hospital (12%), and
      Veterans Affairs or military hospital (9%). Only 8.6% believed all patients with
      IDA should be screened for CD. Respondents who had completed their fellowship
      within 5 years were more likely than more experienced clinicians to believe that
      all patients with IDA should receive CD screening (OR, 2.8; CI; 1.1-7.5; P=.04).
      Having a higher volume of IDA patients per month also increased the likelihood of
      testing (P=.01). In multivariate analysis, specialists in malignant hematology
      (OR, 3.2; CI, 1.1-9.5; P=.04) and oncologists (OR, 3.5; CI, 1.3-9.5; P=.02) were
      more likely than specialists in benign hematology to screen all patients for CD,
      as were those who saw predominately pediatric patients with IDA vs adult patients
      (OR, 16.9; CI, 3.0-97.0; P=.002). CONCLUSIONS: Practicing hematologists
      infrequently screen for CD in IDA. Physicians who have recently finished their
      fellowship and those who see a high volume of patients with IDA are more likely
      to screen for CD.

PMID- 24892256
TI  - Biomarkers in castration-resistant prostate cancer.

PMID- 24892257
TI  - Diagnosis of von Willebrand disease in people with type O blood.

PMID- 24892258
TI  - New research on the treatment of small HER2-positive breast cancers.

PMID- 24892259
TI  - Maintenance therapy in multiple myeloma.

PMID- 24892261
TI  - Low CD34 dose is associated with poor survival after reduced-intensity
      conditioning allogeneic transplantation for acute myeloid leukemia and
      myelodysplastic syndrome.
AB  - Reduced-intensity conditioning/nonmyeloablative conditioning regimens are
      increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports
      have shown CD34(+) dose to be important for transplantation outcome using
      myeloablative conditioning. The role of CD34(+) dose of peripheral blood
      progenitor cells (PBPC) has not been previously analyzed in a large population
      undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054
      patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic
      syndrome who underwent transplantation between 2002 and 2011. Results of
      multivariate analysis showed that PBPC from HLA-matched siblings containing <4 *
      10(6) CD34(+)/kg was associated with higher nonrelapse mortality (hazard ratio
      [HR], 2.03; P = .001), overall mortality (HR, 1.48; P = .008), and lower
      neutrophil (odds ratio [OR], .76; P = .03) and platelet (OR, .76; P = .03)
      recovery. PBPC from unrelated donors with CD34(+) dose < 6 * 10(6) CD34(+)/kg was
      also associated with higher nonrelapse (HR, 1.38; P = .02) and overall mortality
      (HR, 1.20; P = .05). In contrast to reports after myeloablative HCT, CD34(+) dose
      did not affect relapse or graft-versus-host disease with either donor type. An
      upper cell dose limit was not associated with adverse outcomes. These data
      suggest that PBPC CD34(+) doses >4 * 10(6) CD34(+)/kg and >6 * 10(6) CD34(+)/kg
      are optimal for HLA-matched sibling and unrelated donor HCT, respectively. 

PMID- 24892262
TI  - Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts
      poor outcomes.
AB  - Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight
      gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of
      neutrophil recovery after hematopoietic cell transplantation (HCT). In this
      study, we evaluated the incidence, clinical features, risk factors, and outcomes
      of ES in children and adults undergoing first-time allogeneic HCT. Among 927
      patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to
      12) after HCT. ES patients experienced significantly higher cumulative incidence
      of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P < .001) and higher
      nonrelapse mortality at 2 years (38% versus 19%, P < .001) compared with non-ES
      patients, resulting in lower overall survival at 2 years (38% versus 54%, P <
      .001). There was no significant difference in relapse at 2 years (26% versus 31%,
      P = .772). Suppression of tumorigenicity 2, interleukin 2 receptor alpha, and
      tumor necrosis factor receptor 1 plasma biomarker levels were significantly
      elevated in ES patients. Our results illustrate the clinical significance and
      prognostic impact of ES on allogeneic HCT outcomes. Despite early recognition of
      the syndrome and prompt institution of corticosteroid therapy, outcomes in ES
      patients were uniformly poor. This study suggests the need for a prospective
      approach of collecting clinical features combined with correlative laboratory
      analyses to better characterize ES. 

PMID- 24892264
TI  - A 4-year implementation strategy of aggressive post-resuscitation care and
      temperature management after cardiac arrest.
AB  - BACKGROUND: target temperature management (TTM) not only improves neurological
      outcome and survival but has given momentum to a more aggressive and
      comprehensive treatment after resuscitation. Yet, implementation issues represent
      the main obstacle to systematic treatment with TTM and aggressive post
      resuscitation care. We devised a strategy to introduce, monitor and improve the
      quality of aggressive treatment after resuscitation, including TTM. METHODS:
      standard operative procedures on aggressive post-resuscitation care, written
      jointly by physicians and nurses, were introduced in November 2004. Data of all
      resuscitated patients admitted to the ICU were prospectively acquired for 4
      years. Periodic audits (every 16 months) were programmed, leading to three
      equally long periods. Several critical issues were identified after each audit
      and addressed subsequently, leading to a growing complexity of care. Moreover,
      after 2 years we introduced an educational programme with medical credits for all
      staff attending critically ill patients. Neurological outcome and survival at
      hospital discharged were compared to historical controls of the preceding 22
      months. RESULTS: 129 consecutively resuscitated patients were admitted to the ICU
      in the 4-year study period. Of these, 96 (74%) were treated with TTM and
      aggressive post-resuscitation care. Favourable neurological recovery among
      patients discharged alive significantly improved in the 4-year intervention
      period (81% vs. 50% in historical controls, p<0.01). A composite endpoint of
      mortality and poor neurological outcome also improved (64% vs. 82% respectively,
      p<0.05). Overall survival increased throughout the 4 years, leading to a
      significant improvement in the 3rd period compared to historical controls (60%
      vs. 35%; p<0.05). CONCLUSIONS: we propose a strategy to successfully introduce
      and implement TTM and aggressive post-resuscitation care via standard operative
      procedures, periodic audits and feedback. Continuous education among other
      factors contributed to a significant improvement in neurological outcome and a
      progressive increase in survival.

PMID- 24892265
TI  - The effect of hyperoxia on survival following adult cardiac arrest: a systematic
      review and meta-analysis of observational studies.
AB  - OBJECTIVE: Studies have shown the detrimental effect of hyperoxia in animals with
      return of spontaneous circulation (ROSC) after cardiac arrest. To maximize the
      value of existing clinical studies, we performed the systemic review and meta
      analysis of human observational studies to examine the effect of hyperoxia on
      outcomes of post-ROSC patients. METHODS: We searched PubMed and Embase from the
      inception to October 2013. We selected adult observational studies that compared
      different levels of partial pressure of arterial oxygen (PaO2) in post-ROSC
      patients with mortality or neurological status at hospital discharge as outcome.
      Studies comparing hypoxia with normoxia only were excluded. RESULTS: Fourteen
      studies were identified from 2982 references. Odds ratio (OR) was used as effect
      estimate. OR was reconstructed if not provided in original articles. Hyperoxia
      was defined as a PaO2>300 mmHg. Meta-analysis indicated that hyperoxia appeared
      to be correlated with increased in-hospital mortality (OR, 1.40; 95% CI, 1.02
      1.93; I2, 69.27%; 8 studies) but not worsened neurological outcome (OR, 1.62; 95%
      CI, 0.87-3.02; I2, 55.61%; 2 studies). However, the results were inconsistent in
      subgroup and sensitivity analyses. CONCLUSIONS: Hyperoxia appears to be
      correlated with increased in-hospital mortality of post-ROSC patients. This
      result should be interpreted cautiously because of the significant heterogeneity
      and limited number of studies analyzed. However, because exposure to hyperoxia
      had no obvious benefits, clinicians should monitor PaO2 closely and titrate
      oxygen administration cautiously.

PMID- 24892263
TI  - Etanercept plus topical corticosteroids as initial therapy for grade one acute
      graft-versus-host disease after allogeneic hematopoietic cell transplantation.
AB  - Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the
      beginning of a potentially progressive and fatal course of GVHD after
      hematopoietic stem cell transplantation (HSCT). However, interventional studies
      to treat early GVHD are lacking. We conducted a single-arm prospective phase II
      trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD
      with etanercept and topical corticosteroids would reduce progression to grade 2
      to 4 within 28 days. Study patients (n = 34) had a median age of 51 years (range,
      10 to 67 years) and had undergone unrelated (n = 22) or related (n = 12) donor
      HSCT. Study patients were treated with etanercept (.4 mg/kg, maximum 25 mg/dose)
      twice weekly for 4 to 8 weeks. Ten of 34 patients (29%) progressed to grade 2 to
      4 acute GVHD within 28 days. The cumulative incidence of grade 2 to 4 and grade 3
      to 4 acute GVHD at 1 year was 41% and 3%, respectively. Nonrelapse mortality was
      19% and overall survival was 63% at 2 years. Among a contemporaneous control
      cohort of patients who were diagnosed with grade 1 acute GVHD and treated with
      topical corticosteroids but not etanercept during the study period, 12 of 28
      patients (43%) progressed to grade 2 to 4 GVHD within 28 days, with a 1-year
      incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P =
      .08) and 18% (3% versus 18%, P = .05), respectively. Patients treated with
      etanercept also experienced less increase in GVHD plasma biomarkers suppression
      of tumorigenicity 2 (P = .06) and regenerating islet-derived 3-alpha (P = .01) 28
      days after grade 1 acute GVHD diagnosis compared with contemporaneous control
      patients. This study was terminated early because of poor accrual. Future
      prospective studies are needed to identify patients with grade 1 acute GVHD at
      risk of swift progression to more severe GVHD and to establish consensus for the
      treatment of grade 1 acute GVHD. This trial is registered with
      ClinicalTrials.gov, number NCT00726375. 

PMID- 24892266
TI  - Neuromuscular blockade during therapeutic hypothermia after cardiac arrest:
      observational study of neurological and infectious outcomes.
AB  - INTRODUCTION: Neuromuscular blockade (NMB) is widely used during therapeutic
      hypothermia (TH) after cardiac arrest but its effect on patient outcomes is
      unclear. We compared the effects of NMB on neurological outcomes and frequency of
      early-onset pneumonia in cardiac-arrest survivors managed with TH. METHODS: We
      retrospectively studied consecutive adult cardiac-arrest survivors managed with
      TH in a tertiary-level intensive care unit between January 2008 and July 2013.
      Patients given continuous NMB for persistent shivering were compared to those
      managed without NMB. Cases of early-onset pneumonia and vital status at ICU
      discharge were recorded. To avoid bias due to between-group baseline differences,
      we adjusted the analysis on a propensity score. RESULTS: Of 311 cardiac-arrest
      survivors, 144 received TH, including 117 with continuous NMB and 27 without
      NMBs. ICU mortality was lower with NMB (hazard ratio [HR], 0.54 [0.32; 0.89],
      p=0.016) but the difference was not significant after adjustment on the
      propensity score (HR, 0.70 [0.39; 1.25], p=0.22). The proportion of patients with
      good neurological outcomes was not significantly different (36% with and 22%
      without NMB, p=0.16). Early-onset pneumonia was more common with NMB (HR, 2.36
      [1.24; 4.50], p=0.009) but the difference was not significant after adjustment on
      the propensity score (HR, 1.68 [0.90; 3.16], p=0.10). CONCLUSIONS: Continuous
      intravenous NMB during TH after cardiac arrest has potential owns effects on ICU
      survival with a trend increase in the frequency of early-onset pneumonia.
      Randomised controlled trials are needed to define the role for NMB among
      treatments for TH-induced shivering.

PMID- 24892268
TI  - No gold standard for neurocognitive outcome assessment of drowned children.

PMID- 24892267
TI  - The association between a quantitative computed tomography (CT) measurement of
      cerebral edema and outcomes in post-cardiac arrest-a validation study.
AB  - AIM: Previous studies have examined the association between quantitative head
      computed tomography (CT) measures of cerebral edema and patient outcomes
      reporting that a calculated gray matter to white matter attenuation ratio (GWR)
      of <1.2 indicates a near 100% non-survivable injury post-cardiac arrest. The
      objective of the current study was to validate whether a GWR <1.2 reliably
      indicates poor survival post-cardiac arrest. We also sought to determine the
      inter-rater variability among reviewers, and examine the utility of a novel GWR
      measurement to facilitate easier practical use. METHODS: We performed a
      retrospective analysis of post-cardiac arrest patients admitted to a single
      center from 2008 to 2012. Inclusion criteria were age >=18 years, non-traumatic
      arrest, and available CT imaging within 24h after ROSC. Three independent
      physician reviewers from different specialties measured CT attenuation of pre
      specified gray and white matter areas for GWR calculations. RESULTS: Out of 171
      consecutive patients, 90 met the study inclusion criteria. Thirteen patients were
      excluded for technical reasons and/or significant additional pathology, leaving
      77 head CT scans for evaluation. Median age was 66 years and 64% were male. In
      hospital mortality was 65% and 70% of patients received therapeutic hypothermia.
      For the validation measurement, the intra-class correlation coefficient was 0.70.
      In our dataset, a GWR below 1.2 did not accurately predict mortality or poor
      neurological outcome (sensitivity 0.56-0.62 and specificity 0.63-0.81). A score
      below 1.1 predicted a near 100% mortality but was not a sensitive metric
      (sensitivity 0.14-0.20 and specificity 0.96-1.00). Similar results were found for
      the exploratory model. CONCLUSION: A GWR <1.2 on CT imaging within 24h after
      cardiac arrest was moderately specific for poor neurologic outcome and mortality.
      Based on our data, a threshold GWR <1.1 may be a safer cut-off to identify
      patients with low chance of survival and good neurological outcome. Intra-class
      correlation among reviewers was moderately good.

PMID- 24892269
TI  - A systematic review of the effect of emergency medical service practitioners'
      experience and exposure to out-of-hospital cardiac arrest on patient survival and
      procedural performance.
AB  - BACKGROUND AND OBJECTIVE: Emergency medical service (EMS) practitioners'
      experience and exposure to out-of-hospital cardiac arrest (OHCA) and advanced
      life support (ALS) procedures could be an important factor in procedural success
      and patient survival. We systematically reviewed the literature to examine these
      associations. METHODOLOGY: We searched for publications using MEDLINE, EMBASE,
      CINAHL, CENTRAL and Web of Science. We included studies examining any type of EMS
      practitioner (e.g. paramedics, physicians) and OHCA patients of all ages and
      aetiologies. Two reviewers independently extracted data. RESULTS: The search
      identified 1658 citations, of which 11 observational studies of variable quality
      were included. The majority of studies did not adjust for important confounding
      factors and reported across different EMS personnel structures. OHCA survival was
      not consistently associated with various definitions of career experience in
      three studies, or with previous OHCA exposure in another study. Endotracheal
      intubation (ETI) was the only ALS procedure examined. Successful ETI placement
      was associated with the previous number of ETIs performed in four of five
      studies, but not career experience in three of four studies. Only one study
      examined OHCA outcome, and reported an increase in survival to hospital discharge
      when practitioners had high ETI exposure. CONCLUSIONS: There is no clear evidence
      of an association with EMS practitioner career experience or exposure to OHCA
      cases and ALS procedures, with the exception of exposure to ETI and successful
      placement. However, most studies in this field had substantial risk of bias.
      Therefore, further studies are required before any definitive conclusions can be
      drawn.

PMID- 24892270
TI  - Antioxidant and hepatoprotective activity of Veronica ciliata Fisch. extracts
      against carbon tetrachloride-induced liver injury in mice.
AB  - Veronica ciliata Fisch. has been traditionally used in Traditional Chinese
      Medicine prescriptions due to its curative effects for hepatitis, cholecystitis,
      rheumatism, and urticaria. The present study was focused on investigating the
      role of ethyl acetate and aqueous extracts of Veronica ciliata Fisch.
      Furthermore, in vitro antioxidant activity (scavenging of DPPH, ABTS, superoxide,
      and nitrite radicals; reducing power; beta-carotene bleaching) and the
      hepatoprotective effect of the ethyl acetate extract by means of CCl4-induced
      oxidative stress in mice were investigated. The ethyl acetate extract of Veronica
      ciliata Fisch. displayed more noteworthy in vitro antioxidant activities than the
      aqueous extract. Moreover, it significantly prevented the increase in serum T
      AOC, ALT, AST and ALP level in acute liver damage induced by CCl4, decreased the
      extent of MDA formation in liver and elevated the activities of SOD and GSH in
      liver. This activity was found to be comparable to that of bifendate.
      Histopathological observation of the liver was also performed to further support
      the evidence from the biochemical analysis. The results indicated that strong
      antioxidant activities and a significant protective effect against acute
      hepatotoxicity induced by CCl4 of Veronica ciliata Fisch. were concentrated in
      the ethyl acetate extract. The results suggested that this activity may be due to
      free radical-scavenging and antioxidant properties. 

PMID- 24892271
TI  - Cytokines and chemokines: At the crossroads of cell signalling and inflammatory
      disease.
AB  - Inflammation occurs as a result of exposure of tissues and organs to harmful
      stimuli such as microbial pathogens, irritants, or toxic cellular components. The
      primary physical manifestations of inflammation are redness, swelling, heat,
      pain, and loss of function to the affected area. These processes involve the
      major cells of the immune system, including monocytes, macrophages, neutrophils,
      basophils, dendritic cells, mast cells, T-cells, and B-cells. However,
      examination of a range of inflammatory lesions demonstrates the presence of
      specific leukocytes in any given lesion. That is, the inflammatory process is
      regulated in such a way as to ensure that the appropriate leukocytes are
      recruited. These events are in turn controlled by a host of extracellular
      molecular regulators, including members of the cytokine and chemokine families
      that mediate both immune cell recruitment and complex intracellular signalling
      control mechanisms that characterise inflammation. This review will focus on the
      role of the main cytokines, chemokines, and their receptors in the
      pathophysiology of auto-inflammatory disorders, pro-inflammatory disorders, and
      neurological disorders involving inflammation.

PMID- 24892272
TI  - Periodicity and dissipativity for memristor-based mixed time-varying delayed
      neural networks via differential inclusions.
AB  - In this paper, we investigate a class of memristor-based neural networks with
      general mixed delays involving both time-varying delays and distributed delays.
      By using the Mawhin-like coincidence theorem, together with the differential
      inclusion theory, M-matrix properties and differential inequality techniques,
      some novel criteria are established for ensuring the periodicity and
      dissipativity for the addressed neural networks. Finally, two numerical examples
      with simulations are presented to demonstrate the effectiveness of the
      theoretical results. 

PMID- 24892273
TI  - Comparing fixed and variable-width Gaussian networks.
AB  - The role of width of Gaussians in two types of computational models is
      investigated: Gaussian radial-basis-functions (RBFs) where both widths and
      centers vary and Gaussian kernel networks which have fixed widths but varying
      centers. The effect of width on functional equivalence, universal approximation
      property, and form of norms in reproducing kernel Hilbert spaces (RKHS) is
      explored. It is proven that if two Gaussian RBF networks have the same input
      output functions, then they must have the same numbers of units with the same
      centers and widths. Further, it is shown that while sets of input-output
      functions of Gaussian kernel networks with two different widths are disjoint,
      each such set is large enough to be a universal approximator. Embedding of RKHSs
      induced by "flatter" Gaussians into RKHSs induced by "sharper" Gaussians is
      described and growth of the ratios of norms on these spaces with increasing input
      dimension is estimated. Finally, large sets of argminima of error functionals in
      sets of input-output functions of Gaussian RBFs are described. 

PMID- 24892274
TI  - Chronic Conjunctivitis due to Nocardia nova Complex Formation on a Silicone
      Stent: A Case Report and Review of the Literature.
AB  - Nocardial conjunctivitis associated with silicone tubing is an extremely rare
      finding. The authors present a case of a 52-year-old woman with previous
      dacryocystorhinostomy and silicone tube placement 3 years prior who presented
      with OD redness and discharge for 1 week. On examination, the patient was noted
      to have mucoid discharge and crusting surrounding the silicone tube. The tube
      debris was sampled, and the culture was positive for Nocardia nova complex
      sensitive to trimethoprim/sulfamethoxazole and amikacin. Silicone tube
      colonization and N. nova complex conjunctivitis are both rare but should be
      considered in the differential diagnosis of patients with indwelling silicone
      tubes presenting with chronic conjunctivitis resistant to fluoroquinolones and
      tobramycin. 

PMID- 24892276
TI  - Atypical Presentation of Low-Grade Small Lymphocytic Lymphoma of the Lacrimal
      Sac.
AB  - Lymphoma of the lacrimal sac is uncommon and usually presents as a lacrimal sac
      mass, against a background of known systemic lymphoma. This study presents the
      case of a 70-year-old man with small lymphocytic lymphoma of the lacrimal sac and
      widespread systemic involvement presenting as common canalicular obstruction
      without a palpable mass or systemic symptoms. 

PMID- 24892275
TI  - Orbital Involvement by NUT Midline Carcinoma.
AB  - A 32-year-old female presented with a sino-orbital lesion that proved to be a NUT
      midline carcinoma. This is only the third case of orbital involvement by this
      aggressive lesion. The clinical, radiographic, and histopathologic features of
      NUT midline carcinoma are discussed, as well as its management options. 

PMID- 24892277
TI  - Characterization of dacryops infections.
AB  - PURPOSE: The purpose of this study was to characterize the clinical entity of
      dacryops infections through imaging with or without histopathology in the
      differential of ocular adnexal masses in the setting of infection. METHODS: A
      retrospective chart review was performed on 5 patients seen at 1 clinical
      practice in which a complete ophthalmologic examination and imaging of the lesion
      had been obtained. Two of these patients additionally obtained surgical
      intervention with histopathologic examination. RESULTS: The main lacrimal gland
      was involved in all 5 patients with dacryops infection presenting unilaterally.
      The average age of the patients was 44.6 years. Predisposing factors of eyelid
      margin disease, conjunctivitis, and contact lens usage were highlighted. CT
      provided useful information on the location and size of the lesion. Excision with
      or without marsupialization appears to prevent recurrence and provides a
      histopathologic diagnosis although spontaneous (or self-induced) drainage of the
      cyst in addition to antibiotic therapy can successfully manage the infection and
      cyst size, wherein affected individuals may not pursue further surgical
      management. CONCLUSIONS: Dacryops infection is a rare but important consideration
      in the differential of a mass lesion in the upper fornix associated with
      inflammation that may be confused with orbital cellulitis or abscess. Orbital
      imaging is helpful in delineating the extent of the lesion, whereas surgical
      excision with histopathology can confirm the diagnosis. The authors described 5
      cases with this acute presentation and highlighted concomitant factors that may
      predispose certain patients to the development of infection.

PMID- 24892278
TI  - Punctal stenosis: histopathology, immunology, and electron microscopic features-a
      step toward unraveling the mysterious etiopathogenesis.
AB  - PURPOSE: To study the histologic, immunohistochemical, and electron microscopic
      features of puncta and proximal vertical canaliculi to understand the
      etiopathogenesis of punctal stenosis. METHODS: Prospective study of 26 stenosed
      punctae that were collected following a punctoplasty. Sixteen were from lower
      eyelid and 10 from upper eyelid. Histopathological examination was performed on
      20 punctae using hematoxylin-eosin, periodic acid-Schiff, and Masson trichrome
      staining. Immunohistochemical patterns were analyzed after staining with
      leukocyte common antigen or CD45, CD3, CD5, CD10, CD20, CD138, and smooth muscle
      actin. Six punctae (3 upper, 3 lower) were separately processed for electron
      microscopic studies as per standard protocols. RESULTS: All punctae showed
      evidence of subepithelial and subconjunctival fibrosis. Thirty percent (6/20)
      showed extensive fibrosis. Inflammation was noted in 80% (16/20) of the samples;
      however, 20% (4/20) showed severe inflammation. Strong immunoreactivity was
      noted, with CD45 and CD3 in 80% (16/20) with predominance in the subepithelial
      areas. Focal immunoreactivity was noted for CD10, CD20, and CD138.
      Immunoreactivity was negative for CD5. Electron microscopic features include
      blunted epithelial microvilli, numerous fibroblasts, extensive and irregularly
      arranged collagen bundles, mononuclear infiltration in the vicinity of
      fibroblasts or in between collagen bundles, and inter- and intracellular edema in
      areas of inflammation. CONCLUSIONS: Chronic inflammation and subsequent fibrosis
      appear to be the basic ultrastructural response to various noxious stimuli.
      Mononuclear inflammatory infiltration in the vicinity of fibroblasts could
      possibly reflect a close cellular interaction between these 2 cells.

PMID- 24892279
TI  - Dubowitz syndrome is a complex comprised of multiple, genetically distinct and
      phenotypically overlapping disorders.
AB  - Dubowitz syndrome is a rare disorder characterized by multiple congenital
      anomalies, cognitive delay, growth failure, an immune defect, and an increased
      risk of blood dyscrasia and malignancy. There is considerable phenotypic
      variability, suggesting genetic heterogeneity. We clinically characterized and
      performed exome sequencing and high-density array SNP genotyping on three
      individuals with Dubowitz syndrome, including a pair of previously-described
      siblings (Patients 1 and 2, brother and sister) and an unpublished patient
      (Patient 3). Given the siblings' history of bone marrow abnormalities, we also
      evaluated telomere length and performed radiosensitivity assays. In the siblings,
      exome sequencing identified compound heterozygosity for a known rare nonsense
      substitution in the nuclear ligase gene LIG4 (rs104894419, NM_002312.3:c.2440C>T)
      that predicts p.Arg814X (MAF:0.0002) and an NM_002312.3:c.613delT variant that
      predicts a p.Ser205Leufs*29 frameshift. The frameshift mutation has not been
      reported in 1000 Genomes, ESP, or ClinSeq. These LIG4 mutations were previously
      reported in the sibling sister; her brother had not been previously tested.
      Western blotting showed an absence of a ligase IV band in both siblings. In the
      third patient, array SNP genotyping revealed a de novo ~ 3.89 Mb interstitial
      deletion at chromosome 17q24.2 (chr 17:62,068,463-65,963,102, hg18), which
      spanned the known Carney complex gene PRKAR1A. In all three patients, a median
      lymphocyte telomere length of <= 1st centile was observed and radiosensitivity
      assays showed increased sensitivity to ionizing radiation. Our work suggests
      that, in addition to dyskeratosis congenita, LIG4 and 17q24.2 syndromes also
      feature shortened telomeres; to confirm this, telomere length testing should be
      considered in both disorders. Taken together, our work and other reports on
      Dubowitz syndrome, as currently recognized, suggest that it is not a unitary
      entity but instead a collection of phenotypically similar disorders. As a
      clinical entity, Dubowitz syndrome will need continual re-evaluation and re
      definition as its constituent phenotypes are determined.

PMID- 24892280
TI  - Gestational diabetes mellitus in Africa: a systematic review.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is any degree of impaired glucose
      tolerance first recognised during pregnancy. Most women with GDM revert to normal
      glucose metabolism after delivery of their babies; however, they are at risk of
      developing type 2 diabetes later in life as are their offspring. Determining a
      country's GDM prevalence can assist with policy guidelines regarding GDM
      screening and management, and can highlight areas requiring research. This
      systematic review assesses GDM prevalence in Africa. METHODS AND FINDINGS: Three
      electronic databases were searched without language restrictions; PubMed, Scopus
      and the Cochrane Library. Thirty-one search terms were searched. Eligible
      articles defined GDM, stated what GDM screening approaches were employed and
      reported GDM prevalence. The reporting quality and risk of bias within each study
      was assessed. The PRISMA guidelines for systematic reviews were followed. The
      literature search identified 466 unique records. Sixty full text articles were
      reviewed of which 14 were included in the systematic review. One abstract, for
      which the full text article could not be obtained, was also included. Information
      regarding GDM classification, screening methods and prevalence was obtained for
      six African countries; Ethiopia (n = 1), Morocco (n = 1), Mozambique (n = 1),
      Nigeria (n = 6), South Africa (n= 4) and Tanzania (n = 1). Prevalence figures
      ranged from 0% (Tanzania) to 13.9% (Nigeria) with some studies focussing on women
      with GDM risk factors. Most studies utilised the two hour 75 g oral glucose
      tolerance test and applied the World Health Organization's diagnostic criteria.
      CONCLUSIONS: Six countries, equating to 11% of the African continent, were
      represented in this systematic review. This indicates how little is known about
      GDM in Africa and highlights the need for further research. Considering the
      increasing public health burden of obesity and type 2 diabetes, it is essential
      that the extent of GDM is understood in Africa to allow for effective
      intervention programmes.

PMID- 24892281
TI  - Follow-up of post-discharge growth and mortality after treatment for severe acute
      malnutrition (FuSAM study): a prospective cohort study.
AB  - BACKGROUND: Management of Severe Acute Malnutrition (SAM) plays a vital role in
      achieving global child survival targets. Effective treatment programmes are
      available but little is known about longer term outcomes following programme
      discharge. METHODS: From July 2006 to March 2007, 1024 children (median age 21.5
      months, IQR 15-32) contributed 1187 admission episodes to an inpatient-based SAM
      treatment centre in Blantyre, Malawi. Long term outcomes, were determined in a
      longitudinal cohort study, a year or more after initial programme discharge. We
      found information on 88%(899/1024). RESULTS: In total, 42%(427/1024) children
      died during or after treatment. 25%(105/427) of deaths occurred after normal
      programme discharge, >90 days after admission. Mortality was greatest among HIV
      seropositive children: 62%(274/445). Other risk factors included age <12 months;
      severity of malnutrition at admission; and disability. In survivors, weight-for
      height and weight-for-age improved but height-for-age remained low, mean -2.97 z
      scores (SD 1.3). CONCLUSIONS: Although SAM mortality in this setting was
      unacceptably high, our findings offer important lessons for future programming,
      policy and research. First is the need for improved programme evaluation: most
      routine reporting systems would have missed late deaths and underestimated total
      mortality due to SAM. Second, a more holistic view of SAM is needed: while
      treatment will always focus on nutritional interventions, it is vital to also
      identify and manage underlying clinical conditions such as HIV and disability.
      Finally early identification and treatment of SAM should be emphasised: our
      results suggest that this could improve longer term as well as short term
      outcomes. As international policy and programming becomes increasingly focused on
      stunting and post-malnutrition chronic disease outcomes, SAM should not be
      forgotten. Proactive prevention and treatment services are essential, not only to
      reduce mortality in the short term but also because they have potential to impact
      on longer term morbidity, growth and development of survivors.

PMID- 24892282
TI  - Construct and criterion validity of the Euro Qol-5D in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To investigate the construct and criterion validity of the Euro Qol-5D
      (EQ-5D), which allows quality-adjusted life-years to be calculated, in patients
      with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients who
      had been followed at the Renji Hospital, School of Medicine, Shanghai Jiao Tong
      University were recruited. Cross-sectional correlations of the EQ-5D with
      equivalent domains in disease-specific health-related quality of life (HRQoL),
      LupusQol, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) measures,
      the Systemic Lupus International Collaborating Clinics Damage Index (SDI), and
      patient characteristics were tested. Discriminant validity to assess the ability
      to distinguish between patients of different disease severity was assessed. There
      also were evaluations of ceiling and floor effects. RESULTS: 240 patients were
      recruited in total. The EQ-5D correlated moderately to strongly with all domains
      of the LupusQoL (r: 0.44-0.7) apart from intimate relationships (r = 0.25) and
      body image (r = 0.18). There was moderate negative correlation between EQ-5D and
      clinical assessment of disease, SLEDAI (r = -0.589) and SDI (r = -0.509). When
      compared with equivalent domains on LupusQoL, there was good construct validity
      in EQ-5D (r: 0.631-0.812). EQ-5D could also discriminate patients with varied
      disease severity (according SLEDAI and SDI). There was no floor effect in EQ-5D
      but the ceiling effect remains strong (34%). CONCLUSION: Our results provide
      sufficient evidence that the EQ-5D displays construct and criterion validity for
      use in SLE patients. Disease-specific measures of HRQoL used alongside may be a
      better choice.

PMID- 24892283
TI  - Inflammation triggers RNA transfer from blood cells to brain neurons.

PMID- 24892284
TI  - Automatic detection of regions in spinach canopies responding to soil moisture
      deficit using combined visible and thermal imagery.
AB  - Thermal imaging has been used in the past for remote detection of regions of
      canopy showing symptoms of stress, including water deficit stress. Stress indices
      derived from thermal images have been used as an indicator of canopy water
      status, but these depend on the choice of reference surfaces and environmental
      conditions and can be confounded by variations in complex canopy structure.
      Therefore, in this work, instead of using stress indices, information from
      thermal and visible light imagery was combined along with machine learning
      techniques to identify regions of canopy showing a response to soil water
      deficit. Thermal and visible light images of a spinach canopy with different
      levels of soil moisture were captured. Statistical measurements from these images
      were extracted and used to classify between canopies growing in well-watered soil
      or under soil moisture deficit using Support Vector Machines (SVM) and Gaussian
      Processes Classifier (GPC) and a combination of both the classifiers. The
      classification results show a high correlation with soil moisture. We demonstrate
      that regions of a spinach crop responding to soil water deficit can be identified
      by using machine learning techniques with a high accuracy of 97%. This method
      could, in principle, be applied to any crop at a range of scales. 

PMID- 24892285
TI  - Identification of genes involved in the biology of atypical teratoid/rhabdoid
      tumours using Drosophila melanogaster.
AB  - Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike
      most other human brain tumours, AT/RT are characterized by inactivation of one
      single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF
      chromatin remodelling complex, which has an important role in the control of cell
      differentiation and proliferation. Little is known, however, about the pathways
      involved in the oncogenic effects of SMARCB1 inactivation, which might also
      represent targets for treatment. Here we report a comprehensive genetic screen in
      the fruit fly that revealed several genes not yet associated with loss of snr1,
      the Drosophila homologue of SMARCB1. We confirm the functional role of identified
      genes (including merlin, kibra and expanded, known to regulate hippo signalling
      pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples.
      These results demonstrate that fly models can be employed for the identification
      of clinically relevant pathways in human cancer. 

PMID- 24892286
TI  - Probability of detecting marine predator-prey and species interactions using
      novel hybrid acoustic transmitter-receiver tags.
AB  - Understanding the nature of inter-specific and conspecific interactions in the
      ocean is challenging because direct observation is usually impossible. The
      development of dual transmitter/receivers, Vemco Mobile Transceivers (VMT), and
      satellite-linked (e.g. GPS) tags provides a unique opportunity to better
      understand between and within species interactions in space and time. Quantifying
      the uncertainty associated with detecting a tagged animal, particularly under
      varying field conditions, is vital for making accurate biological inferences when
      using VMTs. We evaluated the detection efficiency of VMTs deployed on grey seals,
      Halichoerus grypus, off Sable Island (NS, Canada) in relation to environmental
      characteristics and seal behaviour using generalized linear models (GLM) to
      explore both post-processed detection data and summarized raw VMT data. When
      considering only post-processed detection data, only about half of expected
      detections were recorded at best even when two VMT-tagged seals were estimated to
      be within 50-200 m of one another. At a separation of 400 m, only about 15% of
      expected detections were recorded. In contrast, when incomplete transmissions
      from the summarized raw data were also considered, the ratio of complete
      transmission to complete and incomplete transmissions was about 70% for distances
      ranging from 50-1000 m, with a minimum of around 40% at 600 m and a maximum of
      about 85% at 50 m. Distance between seals, wind stress, and depth were the most
      important predictors of detection efficiency. Access to the raw VMT data allowed
      us to focus on the physical and environmental factors that limit a transceiver's
      ability to resolve a transmitter's identity. 

PMID- 24892288
TI  - On-device mobile visual location recognition by using panoramic images and
      compressed sensing based visual descriptors.
AB  - Mobile Visual Location Recognition (MVLR) has attracted a lot of researchers'
      attention in the past few years. Existing MVLR applications commonly use Query-by
      Example (QBE) based image retrieval principle to fulfill the location recognition
      task. However, the QBE framework is not reliable enough due to the variations in
      the capture conditions and viewpoint changes between the query image and the
      database images. To solve the above problem, we make following contributions to
      the design of a panorama based on-device MVLR system. Firstly, we design a
      heading (from digital compass) aware BOF (Bag-of-features) model to generate the
      descriptors of panoramic images. Our approach fully considers the characteristics
      of the panoramic images and can facilitate the panorama based on-device MVLR to a
      large degree. Secondly, to search high dimensional visual descriptors directly on
      mobile devices, we propose an effective bilinear compressed sensing based
      encoding method. While being fast and accurate enough for on-device
      implementation, our algorithm can also reduce the memory usage of projection
      matrix significantly. Thirdly, we also release a panoramas database as well as a
      set of test panoramic quires which can be used as a new benchmark to facilitate
      further research in the area. Experimental results prove the effectiveness of the
      proposed methods for on-device MVLR applications. 

PMID- 24892287
TI  - Bat rabies in France: a 24-year retrospective epidemiological study.
AB  - Since bat rabies surveillance was first implemented in France in 1989, 48
      autochthonous rabies cases without human contamination have been reported using
      routine diagnosis methods. In this retrospective study, data on bats submitted
      for rabies testing were analysed in order to better understand the epidemiology
      of EBLV-1 in bats in France and to investigate some epidemiological trends. Of
      the 3176 bats submitted for rabies diagnosis from 1989 to 2013, 1.96% (48/2447
      analysed) were diagnosed positive. Among the twelve recognised virus species
      within the Lyssavirus genus, two species were isolated in France. 47 positive
      bats were morphologically identified as Eptesicus serotinus and were shown to be
      infected by both the EBLV-1a and the EBLV-1b lineages. Isolation of BBLV in
      Myotis nattereri was reported once in the north-east of France in 2012. The
      phylogenetic characterisation of all 47 French EBLV-1 isolates sampled between
      1989 and 2013 and the French BBLV sample against 21 referenced partial
      nucleoprotein sequences confirmed the low genetic diversity of EBLV-1 despite its
      extensive geographical range. Statistical analysis performed on the serotine bat
      data collected from 1989 to 2013 showed seasonal variation of rabies occurrence
      with a significantly higher proportion of positive samples detected during the
      autumn compared to the spring and the summer period (34% of positive bats
      detected in autumn, 15% in summer, 13% in spring and 12% in winter). In this
      study, we have provided the details of the geographical distribution of EBLV-1a
      in the south-west of France and the north-south division of EBLV-1b with its
      subdivisions into three phylogenetic groups: group B1 in the north-west, group B2
      in the centre and group B3 in the north-east of France. 

PMID- 24892289
TI  - Taxonomic position and phylogeny of the genus Vargasiella (Orchidaceae,
      Vandoideae) based on molecular and morphological evidence.
AB  - Since the description of the Neotropical genus Vargasiella in 1952, its taxonomic
      position has remained unclear, mainly due to a lack of sufficient data. In this
      study, the taxonomic position of Vargasiella was revised based on the outcomes of
      macro- and micromorphological studies, analyses of selected molecular markers and
      ecological methods of niche distribution modeling. The phylogenetic relationships
      were inferred using three DNA markers: matK, trnL-F and ITS sequences. The
      morphological studies included the analysis of macromorphological features of
      herbarium specimens as well as micromorphological examination of preserved
      flowers. The ecological niche modeling was applied to identify the distribution
      of the suitable niches of the studied taxa. The relationships between Vargasiella
      and most similar taxa remain unresolved based on the molecular analysis. The
      outcomes from the morphological studies indicated significant differences between
      Vargasiella, Warrea and Warreopsis. Moreover, a niche shift in response to
      changing climate after the last glacial maximum is observed in Vargasiella, while
      no substantial changes in the occupied habitats were identified in the other
      related taxa. The clocktree of the Zygopetaleae estimated from the matK gene
      indicated that the most recent common ancestors of Vargasiella, Warrea and
      Warreopsis originated in the Miocene, while the divergence time for Vargasiella
      and Warrea was assessed at approximately 5.4 Ma ago. Vargasiella seems to be an
      outshoot of the main branch of evolution of the Zygopetaleae. It is noteworthy
      that the Vargasiella-Warrea dichotomy could have taken place later than the
      divergence of Warreopsis from the mutual lineage. The molecular analysis and
      morphological data suggest that Vargasiella and Warrea could have evolved from a
      common ancestor. Accumulation of morphological differences and acceleration of
      the evolution of Vargasiella were more intensive than in other Warreinae and this
      could probably be synchronized with adaptation to different climatic conditions. 

PMID- 24892291
TI  - Quadrupolar ion excitation for radiofrequency-only mass filter operation.
AB  - Trajectory calculations are used to model a mass filter based on the
      radiofrequency (rf)-only operation of a linear quadrupole with resonant
      quadrupole excitation of ions (resonant excitation applied with the same spatial
      electric field as the main quadrupole rf field). Ions are not trapped, but pass
      continuously through the quadrupole. Excited ions gain axial kinetic energy in
      the fringe field at the quadrupole exit, overcome a stopping potential and are
      transmitted to an external detector. No quadrupole direct current is required,
      unlike conventional operation at the tip of the first stability diagram.
      Quadrupole excitation can be applied with amplitude or frequency modulation of
      the main rf voltage, or with an auxiliary excitation voltage. All three methods
      give the same mass resolution. The mass resolution, R, is given by R ~
      0.5q(dbeta/dq)n where q is a Mathieu parameter, beta(q), determines the frequency
      of ion oscillation and n is the number of cycles of the rf field experienced by
      an ion, determined by the flight time through the quadrupole. A disadvantage of
      this mode of operation is that the flight times of the ions and the excitation
      amplitudes or modulation depths need to be synchronized. 

PMID- 24892290
TI  - Identification of maize long non-coding RNAs responsive to drought stress.
AB  - Long non-coding RNAs (lncRNAs) represent a class of riboregulators that either
      directly act in long form or are processed to shorter miRNAs and siRNAs. Emerging
      evidence shows that lncRNAs participate in stress responsive regulation. In this
      study, to identify the putative maize lncRNAs responsive to drought stress, 8449
      drought responsive transcripts were first uploaded to the Coding Potential
      Calculator website for classification as protein coding or non-coding RNAs, and
      1724 RNAs were identified as potential non-coding RNAs. A Perl script was written
      to screen these 1724 ncRNAs and 664 transcripts were ultimately identified as
      drought-responsive lncRNAs. Of these 664 transcripts, 126 drought-responsive
      lncRNAs were highly similar to known maize lncRNAs; the remaining 538 transcripts
      were considered as novel lncRNAs. Among the 664 lncRNAs identified as drought
      responsive, 567 were upregulated and 97 were downregulated in drought-stressed
      leaves of maize. 8 lncRNAs were identified as miRNA precursor lncRNAs, 62 were
      classified as both shRNA and siRNA precursors, and 279 were classified as siRNA
      precursors. The remaining 315 lncRNAs were classified as other lncRNAs that are
      likely to function as longer molecules. Among these 315 lncRNAs, 10 are
      identified as antisense lncRNAs and 7 could pair with 17 CDS sequences with near
      perfect matches. Finally, RT-qPCR results confirmed that all selected lncRNAs
      could respond to drought stress. These findings extend the current view on
      lncRNAs as ubiquitous regulators under stress conditions. 

PMID- 24892292
TI  - Development of a miniaturized multi-turn time-of-flight mass spectrometer with a
      pulsed fast atom bombardment ion source.
AB  - A miniaturized multi-turn time-of-flight (TOF) mass spectrometer with a pulsed
      fast atom bombardment (FAB) ion source (FAB-MULTUM) has been designed and
      constructed in order to overcome the drawbacks associated with magnetic sector
      type instruments utilizing a FAB ion source such as size and weight. This
      instrument consists of a pulsed FAB ion source, a multi-turn TOF mass
      spectrometer, a detector, vacuum system, and electronic circuits. The size and
      weight of the system are less than H520 mm x L580 mm x W230 mm and 45 kg
      (including vacuum pumps and electronic circuits). The achieved resolving power
      and mass accuracy of this instrument were > 25000 and about 1 ppm, respectively,
      which are equivalent to those of magnetic sector type instruments, although the
      size and weight are much smaller than those of magnetic sector type instruments.
      The experimental results led us to the conclusion that this instrument enables
      accurate mass measurements and is a powerful tool for the confirmation of
      synthesized compounds. 

PMID- 24892293
TI  - Interactions between naphthenic acids; dependence on molecular structure revealed
      through statistical analysis of ultra-high-resolution electrospray mass spectra.
AB  - Negative-ion electrospray mass spectra of samples of naphthenic acids contain
      peaks due to monomeric species [M-H](-) and dimeric species [2M-H](-). Working
      with a model system, intensities of the dimers were related to the intensities of
      monomers through linear inverse modelling. The statistical approaches
      investigated and the details of their applications to naphthenic acids are
      described here. The statistical analysis gives estimates of the relative
      probabilities of association of all pairs of monomers, where the monomers are
      defined by their accurate masses. The trends observed in these calculated
      probabilities of association exhibit breakpoints in the vicinity of monomers with
      16 carbon atoms. These findings are discussed in terms of hydrophobic effects
      influencing the probability of association of naphthenic acids. 

PMID- 24892294
TI  - The unimolecular chemistry of protonated and deprotonated 2,2-dinitroethene-1,1
      diamine (FOX-7) studied by tandem mass spectrometry and computational chemistry.
AB  - 2,2-Dinitroethene-1,1-diamine (FOX-7) was studied by means of electrospray
      ionization (ESI) and chemical ionization (CI) mass spectrometry in both positive
      and negative ion mode. Detailed mechanisms of unimolecular fragmentations of
      protonated and deprotonated FOX-7 were investigated using high- and low- energy
      collision-induced dissociation (CID) mass spectrometry, neutral fragment
      reionization mass spectrometry and quantum chemistry calculations. In
      deprotonated FOX-7, elimination of the carbodiimide molecule was identified as
      the energetically most favored fragmentation channel, closely resembling the base
      hydrolysis of FOX-7. The dinitromethanide ion is formed during this fragmentation
      as revealed by comparison with CID mass spectra of an isobaric ion prepared by
      the ESI of authentic sodium dinitromethanide. The proton affinity of FOX-7 was
      estimated as 855 kJ mo(-1) by high-accuracy quantum chemistry calculations. This
      value corresponds to protonation at the C-2 position, though the oxygen
      protonated tautomer was found to be nearly isoenergetic in the gas phase. In
      acetonitrile, the nitro group-protonated FOX-7 was found to be significantly less
      stable then its C-2 tautomer. These theoretical findings are clearly reflected in
      differences in fragmentations of ESI- and CI-generated [M+H(]+) ions.
      Interestingly, the consecutive losses of OH? and NO2? radicals instead of a whole
      HNO3 molecule were found to account for the most abundant fragment ion in the
      positive ESI CID mass spectra. In the CI-generated [M+H](+) and [M+D](+) ions,
      substantial internal energy effects upon the CID were observed. 

PMID- 24892295
TI  - Inosine octamer stabilized by alkali earth metal cations - as studied by
      electrospray ionization mass spectrometry.
AB  - By using electrospray ionization mass spectrometry, inosine was found to be able
      to form an octamer stabilized by alkali earth metal cation, namely Ca(2+), Sr(2+)
      and Ba(2+), of which the most stable is that stabilized by Ca(2+) (ion
      [I8+Ca](2+)). It was established that 9-methylhypoxanthine (M) did not form an
      analogical octamer, since ion [M8+Ca](2+) was not detected. On the other hand, 9
      methylhypoxanthine can form "mixed" octamers together with inosine (ions
      [InMm+Ca](2+), n + m = 8, were detected).

PMID- 24892296
TI  - A simplified method for peptide de novo sequencing using (18)O labeling.
AB  - Incorporation of an (18)O atom into a peptide C-terminus by proteolytic cleavage
      in the presence of H2(18)O is one of the most effective ways of enhancing tandem
      mass spectrometry (MS/MS)-based de novo sequencing. Incorporation is usually
      accomplished by procedures including vacuum-assisted drying of tryptic peptides
      extracted from gels, their subsequent reconstitution in a H2(16)O/H2(18)O mixture
      and re-treatment with trypsin. In the present work, we propose a simplified
      procedure for (18)O incorporation into tryptic peptides by adding H2(18)O and
      trypsin to the original digest solution. In comparison to published methods, the
      proposed protocol for peptide de novo sequencing brings significant advantages in
      analysis and workflow with no deterioration in method performance. We show that
      labeling by this simplified method leads to a highlighting of the y-ion fragment
      series in the peptide matrix-assisted laser desorption/ionization (MALDI)- MS/MS
      data, which facilitates MS/MS data interpretation. We also prove that eliminating
      acid extraction of peptides from gels does not result in a decrease in sequence
      coverage or a qualitative loss of particular peptides detectable by MALDI-MS. The
      method was examined by MALDI-MS/MS on bovine serum albumin and recombinant
      histidine kinase CKI1 from Arabidopsis thaliana, and was verified by de novo
      sequencing of tryptic peptides originating from Apodemus sylvaticus salivary
      proteins. 

PMID- 24892298
TI  - The efficiency of trypsin digestion for mass-spectrometry-based identification
      and quantification of oxidized proteins: evaluation of the digestion of oxidized
      bovine serum albumin.
AB  - In bottom-up proteomics approaches, the enzymatic proteolysis step before mass
      spectrometry (MS) analysis is of crucial importance, as only the efficient
      digestion of the protein will ensure its accurate quantification. The structural
      and chemical alterations occurring upon protein oxidation may decrease the
      efficiency of trypsin digestion, compromising the ensuing MS analysis. Herein,
      the efficiency of the trypsin digestion of oxidized bovine serum albumin (BSA)
      was assessed by protein-sequence coverage and the exponentially modified protein
      abundance index (emPAI) algorithm, allowing a comparison of protein abundance in
      samples with different levels of oxidation. Despite the extensive oxidation
      induced to BSA, verified by analysis of protein carbonyls, no significant
      difference in the yield of tryptic peptides from oxidized samples could be
      observed by nano-high-performance liquid chromatography (HPLC) and nano-HPLC7
      electrospray ionization-MS analysis. After a database search, similar protein
      sequence coverage rates were obtained for both treated and control samples. Thus,
      exponentially modified protein abundance index scores confirmed that, regardless
      of being oxidized, the same amount of BSA was present in the sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis bands excised for digestion. The
      obtained results show that the digestion of the control and oxidized samples were
      similar, leading to the conclusion that in-gel proteolysis is not a main
      hindrance for the identification and quantification of oxidized proteins by MS.

PMID- 24892297
TI  - Some preliminary matrix-assisted laser desorption/ionization imaging experiments
      on maternal and fetal sides of human placenta.
AB  - An investigation on placenta proteins has been carried out by matrix-assisted
      laser desorption/ionization (MALDI) ion imaging (II) experiments. This was
      performed by laser irradiation of the maternal and fetal sides of placenta
      tissue. To investigate the possible changes in protein profile due to the
      development of gestational diabetes mellitus (GDM), five placenta samples from
      GDM patients and five placenta samples from healthy pregnant women were analyzed.
      An extensive optimization of the tissue slice treatment and of the matrix
      deposition method was performed. As already observed in MALDI spectra of placenta
      homogenates, and also in the MALDI-II condition, the most abundant peaks are due
      to hemoglobin alpha chain, hemoglobin beta chain and hemoglobin gamma chain.
      However, higher molecular weight protein species were detected in the m/z range
      20,000-47,000. The species at m/z 30335, m/z 31235 and m/z 32000 show some
      differences in their abundance in the maternal and fetal sides of the tissue in
      both classes of subjects under investigation. Comparison with the literature data
      suggest that they can result from the presence of mitochondrial proteins at
      tissue level. 

PMID- 24892299
TI  - Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with
      antitumor efficacy of Rosemary diterpenes in colon and pancreatic cancer.
AB  - Colorectal and pancreatic cancers remain important contributors to cancer
      mortality burden and, therefore, new therapeutic approaches are urgently needed.
      Rosemary (Rosmarinus officinalis L.) extracts and its components have been
      reported as natural potent antiproliferative agents against cancer cells.
      However, to potentially apply rosemary as a complementary approach for cancer
      therapy, additional information regarding the most effective composition, its
      antitumor effect in vivo and its main molecular mediators is still needed. In
      this work, five carnosic acid-rich supercritical rosemary extracts with different
      chemical compositions have been assayed for their antitumor activity both in vivo
      (in nude mice) and in vitro against colon and pancreatic cancer cells. We found
      that the antitumor effect of carnosic acid together with carnosol was higher than
      the sum of their effects separately, which supports the use of the rosemary
      extract as a whole. In addition, gene and microRNA expression analyses have been
      performed to ascertain its antitumor mechanism, revealing that up-regulation of
      the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic
      modulator miR-15b correlate with the antitumor effect of rosemary. Moreover,
      plasmatic miR-15b down-regulation was detected after in vivo treatment with
      rosemary. Our results support the use of carnosic acid-rich rosemary extract as a
      complementary approach in colon and pancreatic cancer and indicate that GCNT3
      expression may be involved in its antitumor mechanism and that miR-15b might be
      used as a non-invasive biomarker to monitor rosemary anticancer effect. 

PMID- 24892301
TI  - Actin polymerization drives polar growth in Arabidopsis root hair cells.
AB  - In plants, the actin cytoskeleton is a prime regulator of cell polarity, growth,
      and cytoplasmic streaming. Tip growth, as observed in root hairs, caulonema, and
      pollen tubes, is governed by many factors, including calcium gradients,
      exocytosis and endocytosis, reactive oxygen species, and the cytoskeleton.
      Several studies indicate that the polymerization of G-actin into F-actin also
      contributes to tip growth. The structure and function of F-actin within the
      apical dome is variable, ranging from a dense meshwork to sparse single
      filaments. The presence of multiple F-actin structures in the elongating apices
      of tip-growing cells suggests that this cytoskeletal array is tightly regulated.
      We recently reported that sublethal concentrations of fluorescently labeled
      cytochalasin could be used to visualize the distribution of microfilament plus
      ends using fluorescence microscopy, and found that the tip region of the growing
      root hair cells of a legume plant exhibits a clear response to the nodulation
      factors secreted by Rhizobium. 1 In this current work, we expanded our analysis
      using confocal microscopy and demonstrated the existence of highly dynamic
      fluorescent foci along Arabidopsis root hair cells. Furthermore, we show that the
      strongest fluorescence signal accumulates in the tip dome of the growing root
      hair and seems to be in close proximity to the apical plasma membrane. Based on
      these findings, we propose that actin polymerization within the dome of growing
      root hair cells regulates polar growth.

PMID- 24892300
TI  - Antisense oligonucleotide induction of progerin in human myogenic cells.
AB  - We sought to use splice-switching antisense oligonucleotides to produce a model
      of accelerated ageing by enhancing expression of progerin, translated from a mis
      spliced lamin A gene (LMNA) transcript in human myogenic cells. The progerin
      transcript (LMNA Delta150) lacks the last 150 bases of exon 11, and is translated
      into a truncated protein associated with the severe premature ageing disease,
      Hutchinson-Gilford progeria syndrome (HGPS). HGPS arises from de novo mutations
      that activate a cryptic splice site in exon 11 of LMNA and result in progerin
      accumulation in tissues of mesodermal origin. Progerin has also been proposed to
      play a role in the 'natural' ageing process in tissues. We sought to test this
      hypothesis by producing a model of accelerated muscle ageing in human myogenic
      cells. A panel of splice-switching antisense oligonucleotides were designed to
      anneal across exon 11 of the LMNA pre-mRNA, and these compounds were transfected
      into primary human myogenic cells. RT-PCR showed that the majority of
      oligonucleotides were able to modify LMNA transcript processing. Oligonucleotides
      that annealed within the 150 base region of exon 11 that is missing in the
      progerin transcript, as well as those that targeted the normal exon 11 donor site
      induced the LMNA Delta150 transcript, but most oligonucleotides also generated
      variable levels of LMNA transcript missing the entire exon 11. Upon evaluation of
      different oligomer chemistries, the morpholino phosphorodiamidate
      oligonucleotides were found to be more efficient than the equivalent sequences
      prepared as oligonucleotides with 2'-O-methyl modified bases on a
      phosphorothioate backbone. The morpholino oligonucleotides induced nuclear
      localised progerin, demonstrated by immunostaining, and morphological nuclear
      changes typical of HGPS cells. We show that it is possible to induce progerin
      expression in myogenic cells using splice-switching oligonucleotides to redirect
      splicing of LMNA. This may offer a model to investigate the role of progerin in
      premature muscle ageing. 

PMID- 24892303
TI  - Photoelectrochemical water oxidation by screen printed ZnO nanoparticle films:
      effect of pH on catalytic activity and stability.
AB  - Nanostructured ZnO films are promising photoanode materials in
      photoelectrochemical water splitting. While such ZnO photoanodes have achieved
      high activity and good light conversion efficiency in the UV spectral region,
      their application in water splitting devices has been hampered by the
      susceptibility of ZnO towards photocorrosion in aqueous electrolytes. We report a
      systematic investigation aimed at optimising the electrolyte solution to improve
      the long-term stability of ZnO photoanodes. A stability diagram, based on the
      band edge positions of ZnO and the pH-dependent photodegradation potentials of
      ZnO (relative to the decomposition of water), indicates that the optimum pH
      operating conditions for ZnO photoanodes lie between pH 9-12.5. To verify this
      prediction experimentally, the activity and long-term stability of uniform screen
      printed nano-ZnO films was tested in a wide range of buffered and non-buffered
      electrolytes (pH 6-13.5). The ZnO films were more active in buffered, than in non
      buffered electrolytes, and the highest activities were observed close to the pKa
      of the phosphate and borate buffers used. Under zero applied potential, these
      screen-printed films achieved the highest reported photocurrents to date (0.42 mA
      cm(-2) at pH 6 and 0.67 mA cm(-2) at pH 10.5) for any pristine or modified ZnO
      based water oxidation catalyst. The films were subjected to 12 h of controlled
      potential electrolysis, in selected electrolytes, under AM 1.5G simulated
      sunlight. The results are in good agreement with calculations based on
      thermodynamic data for ZnO. Films tested at pH 6 and 7 (representing typically
      used operating conditions) degraded rapidly, whereas they exhibited the highest
      stability when tested in a pH 10.5 borate buffer. In this case, 75% of the
      initial photoactivity was preserved after 12 hours, indicating that the lifetime
      of the electrode could be increased by over an order of magnitude compared to
      standard testing conditions. 

PMID- 24892302
TI  - The attitudes to ageing questionnaire: Mokken scaling analysis.
AB  - BACKGROUND: Hierarchical scales are useful in understanding the structure of
      underlying latent traits in many questionnaires. The Attitudes to Ageing
      Questionnaire (AAQ) explored the attitudes to ageing of older people themselves,
      and originally described three distinct subscales: (1) Psychosocial Loss (2)
      Physical Change and (3) Psychological Growth. This study aimed to use Mokken
      analysis, a method of Item Response Theory, to test for hierarchies within the
      AAQ and to explore how these relate to underlying latent traits. METHODS:
      Participants in a longitudinal cohort study, the Lothian Birth Cohort 1936,
      completed a cross-sectional postal survey. Data from 802 participants were
      analysed using Mokken Scaling analysis. These results were compared with factor
      analysis using exploratory structural equation modelling. RESULTS: Participants
      were 51.6% male, mean age 74.0 years (SD 0.28). Three scales were identified from
      18 of the 24 items: two weak Mokken scales and one moderate Mokken scale. (1)
      'Vitality' contained a combination of items from all three previously determined
      factors of the AAQ, with a hierarchy from physical to psychosocial; (2) 'Legacy'
      contained items exclusively from the Psychological Growth scale, with a hierarchy
      from individual contributions to passing things on; (3) 'Exclusion' contained
      items from the Psychosocial Loss scale, with a hierarchy from general to specific
      instances. All of the scales were reliable and statistically significant with
      'Legacy' showing invariant item ordering. The scales correlate as expected with
      personality, anxiety and depression. Exploratory SEM mostly confirmed the
      original factor structure. CONCLUSIONS: The concurrent use of factor analysis and
      Mokken scaling provides additional information about the AAQ. The previously
      described factor structure is mostly confirmed. Mokken scaling identifies a new
      factor relating to vitality, and a hierarchy of responses within three separate
      scales, referring to vitality, legacy and exclusion. This shows what older people
      themselves consider important regarding their own ageing.

PMID- 24892306
TI  - Effects of immersion media and repolishing on color stability and superficial
      morphology of nanofilled composite resin.
AB  - This study evaluated the influence of fluoride mouth rinses and repolishing on
      the superficial morphology and color stability of nanofilled resin. About 150
      specimens were prepared and polished using aluminum oxide discs for 15 s with a
      pressure of 2 kg. The experimental groups were divided according to the immersion
      medium (artificial saliva, 0.5% sodium fluoride, Fluordent Reach, Oral B,
      Fluorgard) and repolishing procedure (without and with). The specimens were
      continuously immersed for 1 week. Thereafter, half of each sample was repolished.
      A color reading was performed after 24 h of immersion in the artificial saliva
      baseline, after continuous immersion, and after repolishing. The superficial
      morphology was examined using scanning electron microscopy (SEM) in a qualitative
      way. Color change (?E) data were submitted to a mixed analysis of variance using
      a Shapiro-Wilk test (p>0.05 for the different immersion media) and Sidak's test
      (p<0.05 for the differences between groups). In the interaction between the
      repolishing and the immersion media, Fluorgard showed a statistical difference
      between the ?E values with and without repolishing (p<0.0001). On the SEM
      observations, both Fluordent Reach and Fluorgard caused degradation of the
      superficial resinous matrix of the composite after continuous immersion. This
      matrix was removed after repolishing. 

PMID- 24892305
TI  - A retrospective cohort study of shift work and risk of incident cancer among
      German male chemical workers.
AB  - OBJECTIVE: Human evidence of carcinogenicity concerning shift work is
      inconsistent. This industry-based cohort study aimed to examine the relationship
      between working in a rotating shift and cancer incidence. METHODS: The cohort
      consisted of male production workers (12 609 shift and 15 219 day), employed in a
      large chemical industry for at least one year between 1995-2005, and residing in
      the German federal state of Rhineland-Palatinate. Incident cancer cases from 2000
      2009 were identified through record linkage with the cancer registry of Rhineland
      Palatinate. Information on exposure to shift work and potential confounders,
      including age, smoking status, job level, and employment duration, was extracted
      from the personnel and health records. Cox proportional hazard models were used
      to estimate hazard ratios (HR) with 95% confidence interval (95% CI) adjusted for
      potential confounders. RESULTS: Between 2000-2009, 518 and 555 cancer cases
      (excluding non-melanoma skin cancer) occurred among shift and day work employees,
      respectively. Compared to "never shift work", shift workers experienced an
      increased risk of cancers neither at all-sites (HR 1.04, 95% CI 0.89-1.21) nor
      for prostate cancer in particular (HR 0.93, 95% CI 0.71-1.21). The risks of
      leukemia and esophagus cancer were increased if smoking was not taken into
      account, albeit based on small numbers. However, adjusting for smoking changed
      the HR and the risk diminished. CONCLUSIONS: Our analyses do not provide evidence
      for a carcinogenic effect of the shift system under study.

PMID- 24892307
TI  - Besnoitia besnoiti and Toxoplasma gondii: two apicomplexan strategies to
      manipulate the host cell centrosome and Golgi apparatus.
AB  - Besnoitia besnoiti and Toxoplasma gondii are two closely related parasites that
      interact with the host cell microtubule cytoskeleton during host cell invasion.
      Here we studied the relationship between the ability of these parasites to invade
      and to recruit the host cell centrosome and the Golgi apparatus. We observed that
      T. gondii recruits the host cell centrosome towards the parasitophorous vacuole
      (PV), whereas B. besnoiti does not. Notably, both parasites recruit the host
      Golgi apparatus to the PV but its organization is affected in different ways. We
      also investigated the impact of depleting and over-expressing the host
      centrosomal protein TBCCD1, involved in centrosome positioning and Golgi
      apparatus integrity, on the ability of these parasites to invade and replicate.
      Toxoplasma gondii replication rate decreases in cells over-expressing TBCCD1 but
      not in TBCCD1-depleted cells; while for B. besnoiti no differences were found.
      However, B. besnoiti promotes a reorganization of the Golgi ribbon previously
      fragmented by TBCCD1 depletion. These results suggest that successful
      establishment of PVs in the host cell requires modulation of the Golgi apparatus
      which probably involves modifications in microtubule cytoskeleton organization
      and dynamics. These differences in how T. gondii and B. besnoiti interact with
      their host cells may indicate different evolutionary paths.

PMID- 24892308
TI  - Transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is defined as the onset or the
      worsening of respiratory distress within 6  h of the transfusion of a plasma
      containing blood component. It is currently considered to be one of the leading
      causes of severe posttransfusion morbidity and acute mortality in countries with
      a high development index. Understanding of the pathogenesis of TRALI has resulted
      in the development of preventive measures that have contributed to reducing its
      incidence. Early recognition of the clinical symptoms allow the clinician to
      identify the syndrome and to undertake therapeutic measures that may reduce the
      morbidity and mortality associated with this complication.

PMID- 24892309
TI  - Incorporating patients with chronic heart failure into outpatient cardiac
      rehabilitation: practical recommendations for exercise and self-care counseling-a
      clinical review.
AB  - PURPOSE: A recent policy change from the Centers for Medicare and Medicaid
      Services includes coverage of cardiac rehabilitation (CR) for patients with
      chronic heart failure (CHF) with reduced ejection fraction. This article provides
      a framework by which CR programs can incorporate disease-specific services for
      patients with CHF who participate in CR. DISCUSSION: Cardiac rehabilitation
      should include self-care counseling that targets improved education and skill
      development (eg, medication compliance, monitoring/management of body weight).
      Various tools are available for assessing exercise tolerance (eg, stress test
      with gas exchange and 6-minute walk), health-related quality of life, and other
      outcome-related parameters. Exercise should be prescribed in a manner that
      progressively increases intensity, duration, and frequency, to a volume of
      exercise equivalent to 3 to 7 metabolic equivalent task (MET)-hr per week. The
      benefits of exercise training are limited by patient adherence; therefore, CR
      providers need to identify the adherence challenges unique to each patient and
      address each accordingly. To optimize the referral of patients with CHF to CR,
      program staff should develop strategies to raise both health care provider and
      patient awareness about the benefits of CR, as well as work collaboratively to
      set up system-based approaches to CR referral. CONCLUSIONS: The referral of
      patients with CHF to CR will increase in 2014 and beyond, due partly to a policy
      change from the Centers for Medicare and Medicaid Services that allows coverage
      for CR. These patients should be integrated into existing programs, with the
      intent of providing both standard CR services and CHF-specific education and
      disease management activities that target improved outcomes.

PMID- 24892310
TI  - Managing dementia symptoms and needs using technology.
AB  - Dementia is a difficult and costly disease to manage. Although caregivers and
      patients have indicated they need support for activities of daily living and
      debilitating neuropsychological symptoms, most technology innovations focus on
      safety and social contact. This feasibility study tested a care technology
      designed to manage dementia symptoms and everyday routines using common,
      nonpharmacological interventions. It was implemented in two formal care
      environments (memory care, assisted living). In Sample 1, independent observers
      decided which symptoms were present or absent in individual residents pre
      intervention and 1 and 2 months during the intervention. In Sample 2, independent
      observers determined the desired status (goals) for individual residents prior to
      intervention and evaluated resident status 1 and 2 months into the intervention.
      The intervention was associated with a reduction in symptoms and progression
      toward wellness goals, suggesting that nondrug interventions for managing
      symptoms and daily routines in dementia can be delivered effectively using
      advanced technology.

PMID- 24892311
TI  - Anticoagulation in long-term care: how can we improve medication monitoring?
AB  - Thromboembolic diseases affect a significant proportion of older adults; however,
      due to the risks and associated adverse events with anticoagulation therapy, this
      population may be less likely to receive the best care. Among anticoagulant
      related events within the nursing home, most involve oral anticoagulant agents
      and occur due to deficiencies in monitoring. With the recent approvals of new
      oral anticoagulant agents dabigatran, rivaroxaban, and apixaban, more options are
      now available for treating thrombotic disorders. Ensuring that all members of the
      health care team are aware of the risks and benefits of these agents is paramount
      to improving the monitoring as well as safety in older adults who are at greatest
      risk for adverse events.

PMID- 24892313
TI  - Climate change and public health in North Carolina: a unique state offers ?a
      unique perspective.

PMID- 24892314
TI  - The pan American health organization: new challenges, new roles, new
      responsibilities.

PMID- 24892315
TI  - HIV and risk behaviors of persons of low socio-economic status, Popayan-Colombia
      (2008-2009).
AB  - OBJECTIVE: To determine HIV presence and risk behaviors of persons of low socio
      economic status in the city of Popayan-Colombia. METHODS: Cross-sectional study;
      between 2008 and 2009, 363 participants of Popayan signed informed consent and
      received pre and post HIV test counseling. Socio-demographic characteristics and
      history of STDs, risk behaviors and previous HIV testing were assessed.
      Descriptive statistics, correlations and multivariate logistic regression were
      calculated. RESULTS: Mean age 33.5+/-10,2; 66 %women. Frequency of HIV-positive
      patients was 3.86 % (95% CI:1.87-5.85), greater in men (7.38%; p= 0.013). Greater
      frequency of HIV-positive patients was observed in people age 29-37, those
      without a stable partner, and those with history of risky alcohol consumption
      (more than five drinks in 2 h). CONCLUSIONS: HIV-positive patients frequency in
      this population was greater than national estimate for general population, aged
      15-49 in Colombia, with even greater frequency in men. This study suggests that
      characteristics associated with low socioeconomic status, in economically active
      population, without a stable partner and with risky alcohol use, can potentially
      increase risk of HIV infection.

PMID- 24892317
TI  - Genetic variants associated with addictive behavior in Colombian addicted and non
      addicted to heroin or cocaine.
AB  - OBJECTIVE: Determine the prevalence and compare some genetic markers involved in
      addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or
      heroin and a control group of non-addicted people matched for gender, age and
      ethnicity. METHODS: A 120 addicts and 120 non-addicts Colombian male were
      surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3,
      SLC6A4, ABCB1, DbetaH and CYP2B6 genes. For the identification of alleles markers
      were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of
      cases and controls was analyzed with 61 AIMs. RESULTS: The age of onset use of
      heroin or coca derivatives (cocaine/crack) was 16.5+/-6 years and 99.2% of them
      consume several illicit drugs. It showed that controls and addicts belong to the
      same ethnic group. Significant differences between addicts and controls in
      relation to schooling, marital status, social security family history of
      substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T
      ABCB1 gene (p= 0.001) were found. CONCLUSION: The present results indicate that
      the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1
      gene, are both associated with addictive behavior to heroin or cocaine.

PMID- 24892316
TI  - Prescribing patterns and economic costs of proton pump inhibitors in Colombia.
AB  - OBJECTIVE: To determine the prescribing patterns for proton pump inhibitors and
      to estimate the economic cost of their use in a group of patients affiliated with
      the Colombian Health System. METHODS: This is a descriptive observational study.
      Data for analysis consisted of prescriptions dispensed between October 1st, 2010
      and October 31st, 2010 and were collected from a systematic database of 4.2
      million members. Socio-demographic variables were considered along with the
      defined daily dose,comedication, convenience of the indication for proton pump
      inhibitor use and costs. RESULTS: In this study, 113,560 prescriptions were
      dispensed in 89 cities, mostly to women (57.6%) with a mean age of 54.4 +/- 18.7
      years; the drugs were omeprazole (n= 111.294; 97.81%),esomeprazole (n= 1.378;
      1.2%), lansoprazole (n= 524; 0.4%), pantoprazole and rabeprazole. The indication
      for 87.349 of the formulas (76.9%) was justified and statistically associated
      with the use of NSAIDs, antithrombotics, corticosteroids, anti-ulcer, antibiotics
      and prokinetics. No justification was found for 26.211 (23.1%) of the
      prescriptions, which were associated with antidiabetics, antihypertensives,
      hypolipidemics and others (p <0.001).The annual justified cost was estimated to
      be US$ 1,654,701 and the unjustified cost was estimated to be U.S. $2,202,590, as
      calculated using the minimum reference prices. DISCUSSION: Each month, the
      Colombian health system is overloaded by unjustified costs that include payments
      for non-approved indications of proton pump inhibitors and for drugs outside the
      list of essential medications. This issue is contributing to rising costs of
      healthcare in Colombia.

PMID- 24892318
TI  - Candida species and other yeasts in the oral cavities of type 2 diabetic patients
      in Cali, Colombia.
AB  - OBJECTIVE: To determine the prevalence of Candida species and to study factors
      associated to oral cavity colonization in patients with type 2 diabetes mellitus.
      METHODS: A total of 107 diabetics were classified into controlled and
      uncontrolled according to glycosylated hemoglobin values. Each patient was
      assessed for stimulated salivary flow rates, pH, and an oral rinse to search for
      yeast. The study also determined the state of oral health via Klein and Palmer
      CPO indexes for permanent dentition, dental plaque by O'Leary, and a periodontal
      chart. RESULTS: We found yeasts in 74.8% of the patients. A total of 36 of the 52
      subjects with controlled diabetes presented yeasts and 44 in the uncontrolled; no
      significant differences (p = 0.2) were noted among the presence of yeasts and the
      control of blood glucose. The largest number of isolates corresponded to C.
      albicans, followed by C. parapsilosis. Uncontrolled individuals presented a
      significantly higher percentage of yeast different from C. albicans (p = 0.049).
      CONCLUSIONS: We found a high percentage of Candida colonization and uncontrolled
      individuals had greater diversity of species. The wide range of CFU/mL found both
      in patients with oral candidiasis, as well as in those without it did not permit
      distinguishing between colonization and disease. We only found association
      between isolation of yeasts and the low rate of salivary flow.

PMID- 24892319
TI  - Regulatory effect of Dimethyl Sulfoxide (DMSO) on astrocytic reactivity in a
      murine model of cerebral infarction by arterial embolization.
AB  - INTRODUCTION: The pathophysiology of cerebral ischemia is essential for early
      diagnosis, neurologic recovery, the early onset of drug treatment and the
      prognosis of ischemic events. Experimental models of cerebral ischemia can be
      used to evaluate the cellular response phenomena and possible neurological
      protection by drugs. OBJECTIVE: To characterize the cellular changes in the
      neuronal population and astrocytic response by the effect of Dimethyl Sulfoxide
      (DMSO) on a model of ischemia caused by cerebral embolism. METHODS: Twenty Wistar
      rats were divided into four groups (n= 5). The infarct was induced with alpha
      bovine thrombin (40 NIH/Unit.). The treated group received 90 mg (100 MUL) of
      DMSO in saline (1:1 v/v) intraperitoneally for 5 days; ischemic controls received
      only NaCl (placebo) and two non-ischemic groups (simulated) received NaCl and
      DMSO respectively. We evaluated the neuronal (anti-NeuN) and astrocytic immune
      reactivity (anti-GFAP). The results were analyzed by densitometry (NIH Image J
      Fiji 1.45 software) and analysis of variance (ANOVA) with the Graph pad software
      (Prism 5). RESULTS: Cerebral embolism induced reproducible and reliable lesions
      in the cortex and hippocampus (CA1)., similar to those of focal models. DMSO did
      not reverse the loss of post-ischemia neuronal immune-reactivity, but prevented
      the morphological damage of neurons, and significantly reduced astrocytic
      hyperactivity in the somato-sensory cortex and CA1 (p <0.001). CONCLUSIONS: The
      regulatory effect of DMSO on astrocyte hyperreactivity and neuronal-astroglial
      cytoarchitecture , gives it potential neuroprotective properties for the
      treatment of thromboembolic cerebral ischemia in the acute phase.

PMID- 24892321
TI  - Vitamin B12 deficit and development of geriatric syndromes.
AB  - Vitamin B12 deficiency or cyanocobalamin is a common condition in the elderly. It
      is repeatedly overlooked due to multiple clinical manifestations that can affect
      the blood, neurological, gastrointestinal, and cardiovascular systems, skin and
      mucous membranes. The various presentations of vitamin B12 deficiency are related
      to the development of geriatric syndromes like frailty, falls, cognitive
      impairment, and geriatric nutritional syndromes like protein-energy malnutrition
      and failure to thrive, in addition to enhancing aging anorexia and cachexia.
      Therefore, interventions must be developed to include their screening and
      diagnosis to make early and appropriate treatment to prevent its complications
      before they become irreversible. 

PMID- 24892320
TI  - Evaluation of an educational, theater-based intervention on attitudes toward
      organ donation in Risaralda, Colombia.
AB  - INTRODUCTION: The shortage of organs for transplantation is a worldwide problem
      and the main cause is the refusal of family members to donate. Consent to donate
      is influenced by many factors and educational interventions are strongly
      recommended. OBJECTIVE: To evaluate the impact of an educational, theaterbased
      strategy on the attitudes toward organ donation. METHODS: This study employed an
      intervention using theater as the central tool. The impact of this intervention
      on the intention to donate was assessed through a controlled, prospective,
      nonrandomized designed study. The sample consisted of 1,038 people. All the
      participants answered a survey that asked about sex, age and intent to donate.
      Afterward, one portion of the sample was exposed to the play, The Gift of Life,
      and a subsequent discussion forum that was guided by experts. The same survey was
      administered again after the intervention. RESULTS: Before the intervention,
      donation attitudes were positive in 68.3% of the responses, negative in 6.8% and
      uncertain in 24.9%. Females showed a greater intent to donate while age had no
      apparent influence on the donation decision. Those exposed to the intervention
      were found to be more likely to donate and show a favorable change in attitude
      toward donation than those who were not exposed to the intervention. CONCLUSION:
      An educational intervention using theater is an effective tool to generate a
      short-term change in the intent to donate. Educational strategies should be
      employed to increase the rates of organ donation.

PMID- 24892322
TI  - Mucocele of the glands of Blandin-Nuhn: a case report.
AB  - Mucoceles arising from the Blandin Nuhn glands are uncommon benign lesions of the
      oral cavity, which by their clinical presentation may be confused with more
      serious diseases such as vascular lesions, pyogenic granulomas, polyps, or
      squamous papillomas; thereby, it is convenient to be aware of the characteristics
      of this entity to guide the accurate and timely diagnosis and treatment. Herein,
      we present a case of a 10-year-old patient with a recurrent lesion of this type,
      which required surgical excision and marsupialization of the same, with no
      evidence of recurrence during follow-up. 

PMID- 24892323
TI  - Functional differences of Porphyromonas gingivalis Fimbriae in determining
      periodontal disease pathogenesis: a literature review.
AB  - Porphyromonas gingivalis is implicated in chronic and aggressive periodontitis.
      This bacterium has numerous virulence factors and one is the Fimbriae, which is
      quite important for bacterial colonization. Fimbriae are appendices that anchor
      to the bacterial wall and are comprised of the protein FimBriline encoded by the
      FimA gene. Thus far, six genotypes have been identified, FimA I to V and Ib.
      Genotypes II and IV are associated with periodontal disease, while genotype I is
      related to gingival health. Genotype identification of P. gingivalis FimA in
      periodontitis would be important to confirm the pathogenic genotypes and to
      establish risk at population level. This review is about the P. gingivalis FimA
      genotype prevalence worldwide. A systematic search using Pubmed, Hinary, and
      Science Direct within the following descriptors: Porphyromonas gingivalis,
      bacterial adhesion, periodontitis, Fimbriae, FimA, genotipification was performed
      to April 2011. 

PMID- 24892325
TI  - From trials to the public health: pre-exposure prophylaxis for HIV prevention.

PMID- 24892324
TI  - An approach to the etiology of metabolic syndrome.
AB  - Increased prevalence of obesity in the world, especially accumulation of abnormal
      amounts of visceral fat predisposes to insulin resistance, which is the central
      role of metabolic syndrome (MS). Obesity can deregulate the intracellular
      signaling of insulin due to the production of inflammatory substances,
      chemoattractant proteins, adipokines and molecules that trigger hormonal mediator
      potentials for destabilization of signal transduction, leading to metabolic
      disorders such as hyperglycemia, hypertension, and dyslipidemia. The complexity
      of the MS and of the genetic mechanisms involved in its etiology derives from the
      combination of variants on genes involved and environmental factors that
      predispose it. The purpose of this paper is to review the effects of obesity in
      molecular and biochemical responses that trigger insulin resistance and its
      relation to some candidate genes and the ancestral component of the population. 

PMID- 24892326
TI  - Dose modification factor analysis of multilumen balloon brachytherapy applicator
      with Monte Carlo simulation.
AB  - The Contura brachytherapy applicator is a silicone balloon with five lumens in
      which a high-dose-rate brachytherapy source can traverse. Multilumen applicators,
      like the Contura, are used in accelerated partial breast irradiation (APBI)
      brachytherapy in instances where asymmetric dose distributions are desired; for
      example, when the applicator surface-to-skin thickness is small (< 7 mm). In
      these instances, the air outside the patient and the lung act as a poor
      scattering medium, scattering less dose back into the breast and affecting the
      dose distribution. The recent report by Task Group 186 of the American
      Association of Physicists in Medicine (AAPM) has outlined the importance of
      moving towards brachytherapy dose calculations using heterogeneity corrections.
      However, at this time, many commercial treatment planning systems do not correct
      for tissue heterogeneity, which can result in inaccuracies in the planned dose
      distribution. To quantify the deviation in the skin dose we utilize the dose
      modification factor (DMF), defined as the ratio of the dose rate at 1 cm beyond
      the applicator surface with homogenous medium, to the dose rate at 1 cm with
      heterogeneous medium. This investigation models the Contura applicator with the
      Monte Carlo N-Particle code version 5, and determines a DMF through simulation.
      Taking all geometrical considerations into account, an accurate model of the
      Contura balloon applicator was created in MCNP and used to run simulations. The
      dose modification factor was found to be only slightly dependent on whether the
      dose distribution was symmetric or asymmetric. These results indicate that the
      dose delivered to part of the PTV may be lower than the planned dose by up to
      12%, and that these brachytherapy plans should be viewed with caution. In
      addition to studying the effects of backscatter, an evaluation was made regarding
      the capabilities of the Contura device to shape an asymmetric dose distribution.
      We compared these results to a previous study of a MammoSite ML and a SAVI device
      and found that the dose shaping capabilities of the Contura were quite similar to
      that of the MammoSite ML, but markedly inferior to the SAVI.

PMID- 24892327
TI  - Efficacy evaluation of retrospectively applying the Varian normal breathing
      predictive filter for volume definition and artifact reduction in 4D CT lung
      patients.
AB  - Phase-based sorting of four-dimensional computed tomography (4D CT) datasets is
      prone to image artifacts due to patient's breathing irregularities that occur
      during the image acquisition. The purpose of this study is to investigate the
      effect of the Varian normal breathing predictive filter (NBPF) as a retrospective
      phase-sorting parameter in 4D CT. Ten 4D CT lung cancer datasets were obtained.
      The volumes of all tumors present, as well as the total lung volume, were
      calculated on the maximum intensity projection (MIP) images as well as each
      individual phase image. The NBPF was varied retrospectively within the available
      range, and changes in volume and image quality were recorded. The patients'
      breathing trace was analysed and the magnitude and location of any breathing
      irregularities were correlated to the behavior of the NBPF. The NBPF was found to
      have a considerable effect on the quality of the images in MIP and single-phase
      datasets. When used appropriately, the NBPF is shown to have the ability to
      account for and correct image artifacts. However, when turned off (0%) or set
      above a critical level (approximately 40%), it resulted in erroneous volume
      reconstructions with variations in tumor volume up to 26.6%. Those phases
      associated with peak inspiration were found to be more susceptible to changes in
      the NBPF. The NBPF settings selected prior to exporting the breathing trace for
      patients evaluated using 4D CT directly affect the accuracy of the targeting and
      volume estimation of lung tumors. Recommendations are made to address potential
      errors in patient anatomy introduced by breathing irregularities, specifically
      deep breath or cough irregularities, by implementing the proper settings and use
      of this tool. 

PMID- 24892328
TI  - Lung tumor motion change during stereotactic body radiotherapy (SBRT): an
      evaluation using MRI.
AB  - The purpose of this study is to investigate changes in lung tumor internal target
      volume during stereotactic body radiotherapy treatment (SBRT) using magnetic
      resonance imaging (MRI). Ten lung cancer patients (13 tumors) undergoing SBRT (48
      Gy over four consecutive days) were evaluated. Each patient underwent three lung
      MRI evaluations: before SBRT (MRI-1), after fraction 3 of SBRT (MRI-3), and three
      months after completion of SBRT (MRI-3m). Each MRI consisted of T1-weighted
      images in axial plane through the entire lung. A cone-beam CT (CBCT) was taken
      before each fraction. On MRI and CBCT taken before fractions 1 and 3, gross tumor
      volume (GTV) was contoured and differences between the two volumes were compared.
      Median tumor size on CBCT before fractions1 (CBCT-1) and 3 (CBCT-3) was 8.68 and
      11.10 cm3, respectively. In 12 tumors, the GTV was larger on CBCT-3 compared to
      CBCT-1 (median enlargement, 1.56 cm3). Median tumor size on MRI-1, MRI-3, and MRI
      3m was 7.91, 11.60, and 3.33 cm3, respectively. In all patients, the GTV was
      larger on MRI-3 compared to MRI-1 (median enlargement, 1.54 cm3). In all
      patients, GTV was smaller on MRI-3m compared to MRI-1 (median shrinkage, 5.44
      cm3). On CBCT and MRI, all patients showed enlargement of the GTV during the
      treatment week of SBRT, except for one patient who showed minimal shrinkage (0.86
      cm3). Changes in tumor volume are unpredictable; therefore, motion and breathing
      must be taken into account during treatment planning, and image-guided methods
      should be used, when treating with large fraction sizes.

PMID- 24892329
TI  - Importance of CBCT setup verification for optical-guided frameless radiosurgery.
AB  - The purpose of this study is to quantify the discrepancy between optical guidance
      platform (OGP) frameless localization system (Varian) and Trilogy on-board
      imaging (OBI) system (Varian) for setting up phantom and stereotactic
      radiosurgery (SRS) patient; and to determine whether cone-beam CT (CBCT) is
      necessary for OGP patient setup, and compare CBCT and orthogonal kV-kV in term of
      their verification capability. Three different phantoms were used in the study: a
      custom-made phantom, a Penta-Guide phantom, and a RANDO phantom. Five patients
      using both OGP and CBCT setup and 14 patients using CBCT setup alone were
      analyzed. One patient who had big couch shifts discrepancy between OGP and CBCT
      was selected for further investigation. Same patient's CBCT and planning CT were
      fused. A RANDO phantom simulation experiment was performed using OGP setup with
      both CBCT and orthogonal kV-kV verification. For all of three phantom
      experiments, the shifts performed by CBCT beam and orthogonal kV-kV were all
      within 1 mm. Among five SRS patients using OGP setup, three had 3D couch
      corrections more than 3 mm. The image fusion of CBCT and planning CT clearly
      illustrated a tilt of bite-block in a patient's mouth. For 14 SRS patients using
      CBCT-guided setup, overall 3D correction was 3.3 +/- 1.5 mm. RANDO phantom
      experiment demonstrated how a tilted bite-block caused isocenter shift. CBCT
      calculated shifts are the same as expected, but kV-kV results differed by 1-2 mm
      if the initial head position is tilted. The bite-block tilting in patient's mouth
      is a major reason for the cause of positioning error for OGP frameless SRS setup.
      CBCT verification is necessary. CBCT provides more accurate couch corrections
      than orthogonal kV-kV when head was tilted. OGP is useful for detecting patient
      movement, but it does not necessarily imply that the isocenter has moved. 

PMID- 24892330
TI  - Detector system dose verification comparisons for arc therapy: couch vs. gantry
      mount.
AB  - The aim of this study was to assess the performance of a gantry-mounted detector
      system and a couch set detector system using a systematic multileaf collimator
      positional error manually introduced for volumetric-modulated arc therapy. Four
      head and neck and esophagus VMAT plans were evaluated by measurement using an
      electronic portal imaging device and an ion chamber array. Each plan was copied
      and duplicated with a 1 mm systematic MLC positional error in the left leaf bank.
      Direct comparison of measurements for plans with and without the error permitted
      observational characteristics for quality assurance performance between
      detectors. A total of 48 different plans were evaluated for this testing. The
      mean percentage planar dose differences required to satisfy a 95% match between
      plans with and without the MLCPE were 5.2% +/- 0.5% for the chamber array with
      gantry motion, 8.12% +/- 1.04% for the chamber array with a static gantry at 0
      degrees , and 10.9%+/- 1.4% for the EPID with gantry motion. It was observed that
      the EPID was less accurate due to overresponse of the MLCPE in the left leaf
      bank. The EPID always images bank-A on the ipsilateral side of the detector,
      whereas for a chamber array or for a patient, that bank changes as it crosses the
      -90 degrees  or +90 degrees  position. A couch set detector system can reproduce
      the TPS calculated values most consistently. We recommend it as the most reliable
      patient specific QA system for MLC position error testing. This research is
      highlighted by the finding of up to 12.7% dose variation for H/N and esophagus
      cases for VMAT delivery, where the mere source of error was the stated clinically
      acceptability of 1 mm MLC position deviation of TG-142. 

PMID- 24892331
TI  - A patient-based dosimetric study of intracavitary and interstitial brachytherapy
      in advanced stage carcinoma of the cervix.
AB  - Intracavitary brachytherapy (ICBT) and interstitial brachytherapy (IB) techniques
      are commonly practiced for treating carcinoma of the cervix, either alone or in
      combination with external beam radiotherapy. Both these brachytherapy techniques
      have their own advantages and limitations in terms of tumor coverage and normal
      tissue sparing. Limited studies have been reported comparing the dosimetric
      features of these two techniques, especially from a single institution. We
      carried out a prospective clinical dosimetric comparison between ICBT and IB for
      patients treated at one center to bring out the inherent dosimetric features of
      these to two techniques. The study was carried out on 26 patients treated with
      ICBT and 55 with IB using CT-based planning. Of the 55 patients treated with IB,
      27 included tandem source loading (IBT) and 28 without the tandem loading (IBWT).
      The high-dose volumes covered by 200% and 180% isodose surfaces were considerably
      larger in ICBT as compared to IB, whereas the treated volume was larger in IB as
      compared to ICBT. The bladder and rectal doses were the highest in ICBT and IBWT,
      respectively. The larger treated volume in IB as compared to ICBT was mainly
      because patients with larger tumor volumes were generally considered for IB. The
      results also indicated that in interstitial brachytherapy, better rectal sparing
      was achieved by including the tandem for treatment delivery. 

PMID- 24892332
TI  - Dosimetric impact of gold markers implanted closely to lung tumors: a Monte Carlo
      simulation.
AB  - We are developing an innovative dynamic tumor tracking irradiation technique
      using gold markers implanted around a tumor as a surrogate signal, a real-time
      marker detection system, and a gimbaled X-ray head in the Vero4DRT. The gold
      markers implanted in a normal organ will produce uncertainty in the dose
      calculation during treatment planning because the photon mass attenuation
      coefficient of a gold marker is much larger than that of normal tissue. The
      purpose of this study was to simulate the dose variation near the gold markers in
      a lung irradiated by a photon beam using the Monte Carlo method. First, the
      single-beam and the opposing-beam geometries were simulated using both water and
      lung phantoms. Subsequently, the relative dose profiles were calculated using a
      stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient
      having gold markers along the anterior-posterior (AP) and right-left (RL)
      directions. For the single beam, the dose at the gold marker-phantom interface
      laterally along the perpendicular to the beam axis increased by a factor of 1.35
      in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the
      entrance dose at the interface along the beam axis increased by a factor of 1.63
      in the water phantom and 1.91 in the lung phantom, while the exit dose increased
      by a factor of 1.00 in the water phantom and 1.12 in the lung phantom,
      respectively. On the other hand, both dose escalations and dose de-escalations
      were canceled by each beam for opposing portal beams with the same beam weight.
      For SBRT patient data, the dose at the gold marker edge located in the tumor
      increased by a factor of 1.30 in both AP and RL directions. In clinical cases,
      dose escalations were observed at the small area where the distance between a
      gold marker and the lung tumor was <= 5 mm, and it would be clinically negligible
      in multibeam treatments, although further investigation may be required. 

PMID- 24892334
TI  - Quantitative assessment by measurement and modeling of mobile target elongation
      in cone-beam computed tomographic imaging.
AB  - The purpose of this study was to assess quantitatively elongation of mobile
      targets in cone-beam CT (CBCT) imaging by measurement and modeling. A
      mathematical model was derived that predicts the measured lengths of mobile
      targets and its dependence on target size and motion patterns in CBCT imaging.
      Three tissue-equivalent targets of differing sizes were inserted in an artificial
      thorax phantom to simulate lung lesions. Respiratory motion was mimicked with a
      mobile phantom that moves in one-dimension along the superior-inferior direction
      at a respiration frequency of 0.24 Hz for eight different amplitudes in the range
      0-40 mm. A mathematical model was derived to quantify the variations in target
      lengths and its dependence on phantom motion parameters in CBCT. Predictions of
      the model were verified by measurement of the lengths of mobile targets in CBCT
      images. The model predicts that target lengths increased linearly with increase
      in speed and amplitude of phantom motion in CBCT. The measured lengths of mobile
      targets imaged with CBCT agreed with the calculated lengths within half-slice
      thickness spatial resolution. The maximal length of a mobile target was
      independent of the frequency and phase of motion. Elongation of mobile targets
      was similar in half-fan and full-fan CBCT for similar motion patterns, as long as
      the targets remained within the imaging view. Mobile targets elongated linearly
      with phantom speed and motion amplitude in CBCT imaging. The model introduced in
      this work assessed quantitatively the variation in target lengths induced by
      motion, which may be a useful tool to consider elongations of mobile targets in
      CBCT applications in diagnostic imaging and radiotherapy. 

PMID- 24892333
TI  - Dosimetric study of uniform scanning proton therapy planning for prostate cancer
      patients with a metal hip prosthesis, and comparison with volumetric-modulated
      arc therapy.
AB  - The main purposes of this study were to 1) investigate the dosimetric quality of
      uniform scanning proton therapy planning (USPT) for prostate cancer patients with
      a metal hip prosthesis, and 2) compare the dosimetric results of USPT with that
      of volumetric-modulated arc therapy (VMAT). Proton plans for prostate cancer
      (four cases) were generated in XiO treatment planning system (TPS). The beam
      arrangement in each proton plan consisted of three fields (two oblique fields and
      one lateral or slightly angled field), and the proton beams passing through a
      metal hip prosthesis was avoided. Dose calculations in proton plans were
      performed using the pencil beam algorithm. From each proton plan, planning target
      volume (PTV) coverage value (i.e., relative volume of the PTV receiving the
      prescription dose of 79.2 CGE) was recorded. The VMAT prostate planning was done
      using two arcs in the Eclipse TPS utilizing 6 MV X-rays, and beam entrance
      through metallic hip prosthesis was avoided. Dose computation in the VMAT plans
      was done using anisotropic analytical algorithm, and calculated VMAT plans were
      then normalized such that the PTV coverage in the VMAT plan was the same as in
      the proton plan of the corresponding case. The dose-volume histograms of
      calculated treatment plans were used to evaluate the dosimetric quality of USPT
      and VMAT. In comparison to the proton plans, on average, the maximum and mean
      doses to the PTV were higher in the VMAT plans by 1.4% and 0.5%, respectively,
      whereas the minimum PTV dose was lower in the VMAT plans by 3.4%. The proton
      plans had lower (or better) average homogeneity index (HI) of 0.03 compared to
      the one for VMAT (HI = 0.04). The relative rectal volume exposed to radiation was
      lower in the proton plan, with an average absolute difference ranging from 0.1%
      to 32.6%. In contrast, using proton planning, the relative bladder volume exposed
      to radiation was higher at high-dose region with an average absolute difference
      ranging from 0.4% to 0.8%, and lower at low- and medium-dose regions with an
      average absolute difference ranging from 2.7% to 10.1%. The average mean dose to
      the rectum and bladder was lower in the proton plans by 45.1% and 22.0%,
      respectively, whereas the mean dose to femoral head was lower in VMAT plans by an
      average difference of 79.6%. In comparison to the VMAT, the proton planning
      produced lower equivalent uniform dose (EUD) for the rectum (43.7 CGE vs. 51.4
      Gy) and higher EUD for the femoral head (16.7 CGE vs. 9.5 Gy), whereas both the
      VMAT and proton planning produced comparable EUDs for the prostate tumor (76.2
      CGE vs. 76.8 Gy) and bladder (50.3 CGE vs. 51.1 Gy). The results presented in
      this study show that the combination of lateral and oblique fields in USPT
      planning could potentially provide dosimetric advantage over the VMAT for
      prostate cancer involving a metallic hip prosthesis. 

PMID- 24892335
TI  - Interplay effect of angular dependence and calibration field size of MapCHECK 2
      on RapidArc quality assurance.
AB  - The purpose of this study is to investigate an effect of angular dependence and
      calibration field size of MapCHECK 2 on RapidArc QA for 6, 8, 10, and 15 MV. The
      angular dependence was investigated by comparing MapCHECK 2 measurements in
      MapPHAN-MC2 to the corresponding Eclipse calculations every 10 degrees  using 10*
      10 cm2 and 3 * 3 cm2 fields. Fourteen patients were selected to make RapidArc
      plans using the four energies, and verification plans were delivered to two
      phantom setups: MapCHECK 2/MapPHAN phantom (MapPHAN QA) and MapCHECK 2 on an
      isocentric mounting fixture (IMF QA). Migration of MapCHECK 2 on IMF was
      simulated by splitting arcs every 10 degrees  and displacing an isocenter of each
      partial arc in the Eclipse system (IMFACTUAL QA). To investigate the effect of
      calibration field size, MapCHECK 2 was calibrated by two field sizes (10 * 10 cm2
      and 3 * 3 cm2) and applied to all QA measurements. The gamma test was implemented
      using criteria of 1%/1 mm, 2%/2 mm, and 3%/3 mm. A mean dose of all compared
      points for each plan was compared with respect to a mean effective field size of
      the RapidArc plan. The angular dependence was considerably high at gantry angles
      of 90 degrees  +/- 10 degrees  and 270 degrees  +/- 10 degrees  (for 10 * 10/3 *
      3 cm2 at 90 degrees , 30.6% +/- 6.6%/33.4%+/- 5.8% (6 MV), 17.3% +/- 5.3%/15.0%
      +/- 6.8% (8 MV), 8.9%+/- 2.9%/7.8% +/- 3.2% (10 MV), and 2.2% +/- 2.3%/-1.3% +/-
      2.6% (15 MV)). For 6 MV, the angular dependence significantly deteriorated the
      gamma passing rate for plans of large field size in MapPHAN QA (< 90% using 3%/3
      mm); however, these plans passed the gamma test in IMFACTUAL QA (> 95%). The
      different calibration field sizes did not make any significant dose difference
      for both MapPHAN QA and IMFACTUAL QA. For 8, 10, and 15 MV, the angular
      dependence does not make any clinically meaningful impact on MapPHAN QA. Both
      MapPHAN QA and IMFACTUAL QA presented clinically acceptable gamma passing rates
      using 3%/3 mm. MapPHAN QA showed better passing rates than IMFACTUAL QA for the
      tighter criteria. The 10 * 10 cm2 calibration showed better agreement for plans
      of small effective field size (< 5 * 5 cm2) in MapPHAN QA. There was no
      statistical difference between IMF QA and IMFACTUAL QA. In conclusion, MapPHAN QA
      is not recommended for plans of large field size, especially for 6 MV, and
      MapCHECK2 should be calibrated using a field size similar to a mean effective
      field size of a RapidArc plan for better agreement for IMF QA. 

PMID- 24892336
TI  - Dosimetric benefits of IMRT and VMAT in the treatment of middle thoracic
      esophageal cancer: is the conformal radiotherapy still an alternative option?
AB  - The purpose of this study is to investigate the dosimetric differences among
      conformal radiotherapy (CRT), intensity-modulated radiotherapy (IMRT), and
      volumetric-modulated radiotherapy (VMAT) in the treatment of middle thoracic
      esophageal cancer, and determine the most appropriate treatment modality. IMRT
      and one-arc VMAT plans were generated for eight middle thoracic esophageal cancer
      patients treated previous with CRT. The planning target volume (PTV) coverage and
      protections on organs at risk of three planning schemes were compared. All plans
      have sufficient PTV coverage and no significant differences were observed, except
      for the conformity and homogeneity. The lung V5, V10, and V13 in CRT were 47.9%
      +/- 6.1%, 36.5% +/- 4.6%, and 33.2% +/- 4.2%, respectively, which were greatly
      increased to 78.2% +/- 13.7% (p < 0.01), 80.8% +/- 14.9% (p < 0.01), 48.4% +/-
      8.2% (p = 0.05) in IMRT and 58.6% +/- 10.5% (p = 0.03), 67.7% +/- 14.0% (p <
      0.01), and 53.0% +/- 10.1% (p < 0.01) in VMAT, respectively. The lung V20 (p =
      0.03) in VMAT and the V30 (p = 0.04) in IMRT were lower than those in CRT. Both
      IMRT and VMAT achieved a better protection on heart. However, the volumes of the
      healthy tissue outside of PTV irradiated by a low dose were higher for IMRT and
      VMAT. IMRT and VMAT also had a higher MU, optimization time, and delivery time
      compared to CRT. In conclusion, all CRT, IMRT, and VMAT plans are able to meet
      the prescription and there is no clear distinction on PTV coverage. IMRT and VMAT
      can only decrease the volume of lung and heart receiving a high dose, but at a
      cost of delivering low dose to more volume of lung and normal tissues. CRT is
      still a feasible option for middle thoracic esophageal cancer radiotherapy,
      especially for the cost-effective consideration.

PMID- 24892337
TI  - Optimization strategies for pulsed low-dose-rate IMRT of recurrent lung and head
      and neck cancers.
AB  - Pulsed low-dose-rate radiotherapy (PLDR) has been proven to be a valid method of
      reirradiation. Previous studies of recurrent cancer radiotherapy were mainly
      based on conventional 3D CRT and VMAT delivery techniques. There are difficulties
      in IMRT planning using existing commercial treatment planning systems (TPS) to
      meet the PLDR protocol. This work focuses on PLDR using ten-field IMRT and a
      commercial TPS for two specific sites: recurrent lung cancers and head and neck
      cancers. Our PLDR protocol requires that the maximum dose to the PTV be less than
      0.4 Gy and the mean dose to be 0.2 Gy per field. We investigated various planning
      strategies to meet the PLDR requirements for 20 lung and head and neck patients.
      The PTV volume for lung cases ranged from 101.7 to 919.4 cm3 and the maximum dose
      to the PTV ranged from 0.22 to 0.39 Gy. The PTV volume for head and neck cases
      ranged from 66.2 to 282.1 cm3 and the maximum dose to the PTV ranged from 0.21 to
      0.39 Gy. With special beam arrangements and dosimetry parameters, it is feasible
      to use a commercial TPS to generate quality PLDR IMRT plans for lung and head and
      neck reirradiation. 

PMID- 24892339
TI  - Geometric and dosimetric uncertainties in intracranial stereotatctic treatments
      for multiple nonisocentric lesions.
AB  - The purpose of this study was to determine the effects of geometric uncertainties
      of patient position on treatments of multiple nonisocentric intracranial lesions.
      The average distance between lesions in patients with multiple targets was
      determined by a retrospective survey of patients with multiple lesions.
      Retrospective patient imaging data from fractionated stereotactic patients were
      used to calculate interfractional and intrafractional patient position
      uncertainty. Three different immobilization devices were included in the
      positioning study. The interfractional and intrafractional patient positioning
      error data were used to calculate the geometric offset of a lesion located at
      varying distances from the mechanical isocenter for treatments of multiple
      lesions with a single arc, assuming that no intrafractional position correction
      is employed during an arc rotation. Dosimetric effects were studied using two
      representative lesions of two sizes, 6 mm and 13 mm maximum dimensions, and
      prescribed to 20 Gy and 18 Gy, respectively. Distances between lesions ranged
      from < 10 mm to 150 mm, which would correspond to a range of isocenter to lesion
      separations of < 10 mm to 75 mm, assuming an isocenter located at the geometric
      mean. In the presence of a full six degree of freedom patient correction system,
      the effects of the intrafractional patient positioning uncertainties were less
      than 1.8 mm (3.6mm) for 1sigma (2sigma) deviations for lesion spacing up to 75 mm
      assuming a quadratic summation of 1sigma and 2sigma. Without the benefit of a six
      DOF correction device, only correcting for three translations, the effects of the
      intrafractional patient positioning uncertainties were within 3.1 mm (7.2 mm) for
      1sigma (2sigma) deviations for distances up to 75 mm. 1sigma and 2sigma
      deviations along all six axes were observed in 3.6% and 0.3%, respectively, of
      974 fractions analyzed. Dosimetric effects for 2 mm and 4 mm offsets were most
      significant for the small lesion with minimum dose (Dmin) decreasing from 20 Gy
      to 13.6 Gy and 5.7 Gy and volume receiving the prescription (V20Gy) reducing from
      100% to 57% and 16%, respectively. The dosimetric effects on the larger lesion
      were less pronounced with Dmin reducing from 18 Gy to 17.5 Gy and 14.2 Gy, and
      V18Gy reducing from 100% to 98.3% and 85.4%, for 2 mm and 4 mm offsets,
      respectively. In the 1sigma scenario (3.6% of patients) angular uncertainties in
      patient positioning can introduce 1.0 mm shifts in the location of the lesion
      position at distances of 75 mm, compared to an isocentric treatment even with a
      full six DOF correction. Without the ability to correct angular positioning
      errors, a lesion positioned 75 mm away from the mechanical isocenter can be
      located in 3.6% of patients > 3.0 mm distant from the planned position.
      Dosimetric results depend upon the distance from isocenter and the size of the
      target. Single isocenter treatments for multiple lesions should be considered
      only when full six DOF corrections can be applied, the intrafractional
      immobilization precision is well quantified, and a PTV expansion is included for
      more distant lesions to account for unavoidable residual patient positioning
      uncertainties.

PMID- 24892338
TI  - Lung and liver SBRT using helical tomotherapy--a dosimetric comparison of fixed
      jaw and dynamic jaw delivery.
AB  - The purpose of the study was to evaluate the time effectiveness and dose
      distribution details of dynamic jaw delivery compared to the regular helical
      tomotherapy delivery mode in stereotactic body radiation therapy (SBRT) of liver
      and lung tumors. Ten patients with liver and ten patients with lung tumors were
      chosen to analyze the dose profiles and treatment times of regular helical
      tomotherapy delivery (2.5cm field width) and new helical tomotherapy mode using
      dynamic jaw delivery with 5 cm field width. A median dose between 24 and 30 Gy
      was delivered in a single fraction. Regular helical tomotherapy took an average
      of 31.9 +/- 6.7 min (lung SBRT) and 41.7 +/- 15.0 min (liver SBRT). A reduction
      in delivery duration of 38.8% to 19.5+/- 2.9 min could be accomplished for lung
      irradiation (p < 0.05) and by 50.8% to 20.5 +/- 6.0 min for liver SBRT (p <
      0.05). Target coverage, as well as conformity and uniformity indices, showed no
      significant differences. No significant increase in organs-at-risk exposure could
      be detected either for lung or liver tumors. Therefore, use of new delivery mode
      with dynamic jaws improves treatment efficiency by reducing beam-on time, while
      maintaining excellent planquality.

PMID- 24892340
TI  - Monte Carlo investigation of collapsed versus rotated IMRT plan verification.
AB  - IMRT QA requires, among other tests, a time-consuming process of measuring the
      absorbed dose, at least to a point, in a high-dose, low-dose-gradient region.
      Some clinics use a technique of measuring this dose with all beams delivered at a
      single gantry angle (collapsed delivery), as opposed to the beams delivered at
      the planned gantry angle (rotated delivery). We examined, established, and
      optimized Monte Carlo simulations of the dosimetry for IMRT verification of
      treatment plans for these two different delivery modes (collapsed versus
      rotated). The results of the simulations were compared to the treatment planning
      system dose calculations for the two delivery modes, as well as to measurements
      taken. This was done in order to investigate the validity of the use of a
      collapsed delivery technique for IMRT QA. The BEAMnrc, DOSXYZnrc, and egs_chamber
      codes were utilized for the Monte Carlo simulations along with the MMCTP system.
      A number of different plan complexity metrics were also used in the analysis of
      the dose distributions in a bid to qualify why verification in a collapsed
      delivery may or may not be optimal for IMRT QA. Following the Alfonso et al.
      formalism, the kfclin,frefQclin,Q correction factor was calculated to correct the
      deviation of small fields from the reference conditions used for beam
      calibration. We report on the results obtained for a cohort of 20 patients. The
      plan complexity was investigated for each plan using the complexity metrics of
      homogeneity index, conformity index, modulation complexity score, and the
      fraction of beams from a particular plan that intersect the chamber when
      performing the QA. Rotated QA gives more consistent results than the collapsed QA
      technique. The kfclin,frefQclin,Qfactor deviates less from 1 for rotated QA than
      for collapsed QA. If the homogeneity index is less than 0.05 then the
      kfclin,frefQclin,Q factor does not deviate from unity by more than 1%. A value
      this low for the homogeneity index can only be obtained with the rotated QA
      technique.

PMID- 24892341
TI  - Monte Carlo modeling of HD120 multileaf collimator on Varian TrueBeam linear
      accelerator for verification of 6X and 6X FFF VMAT SABR treatment plans.
AB  - A Monte Carlo (MC) validation of the vendor-supplied Varian TrueBeam 6 MV
      flattened (6X) phase-space file and the first implementation of the Siebers-Keall
      MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filter
      free (6X FFF) beams) are described. The MC model is validated in the context of
      VMAT patient-specific quality assurance. The Monte Carlo commissioning process
      involves: 1) validating the calculated open-field percentage depth doses (PDDs),
      profiles, and output factors (OF), 2) adapting the Siebers-Keall MLC model to
      match the new HD120-MLC geometry and material composition, 3) determining the
      absolute dose conversion factor for the MC calculation, and 4) validating this
      entire linac/MLC in the context of dose calculation verification for clinical
      VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0%
      for field sizes ranging from 2 * 2 to 40 * 40 cm2. Measured and MC profiles show
      agreement in the 50% field width and the 80%-20% penumbra region to within 1.3 mm
      for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with
      measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra
      plans demonstrate that measured and MC ion chamber doses agree within 0.6% for
      the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis
      demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3
      mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam
      accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in
      Monte Carlo to provide an independent 3D dose calculation for clinical VMAT
      plans. This quality assurance tool has been used clinically to verify over 140 6X
      and 16 6X FFF TrueBeam treatment plans. 

PMID- 24892342
TI  - Evaluation of IsoCal geometric calibration system for Varian linacs equipped with
      on-board imager and electronic portal imaging device imaging systems.
AB  - The purpose of this study is to evaluate the accuracy and reproducibility of the
      IsoCal geometric calibration system for kilovoltage (kV) and megavoltage (MV)
      imagers on Varian C-series linear accelerators (linacs). IsoCal calibration
      starts by imaging a phantom and collimator plate using MV images with different
      collimator angles, as well as MV and kV images at different gantry angles. The
      software then identifies objects on the collimator plate and in the phantom to
      determine the location of the treatment isocenter and its relation to the MV and
      kV imager centers. It calculates offsets between the positions of the imaging
      panels and the treatment isocenter as a function of gantry angle and writes a
      correction file that can be applied to MV and kV systems to correct for those
      offsets in the position of the panels. We performed IsoCal calibration three
      times on each of five Varian C-series linacs, each time with an independent
      setup. We then compared the IsoCal calibrations with a simplified Winston-Lutz
      (WL)-based system and with a Varian cubic phantom (VC)-based system. The maximum
      IsoCal corrections ranged from 0.7 mm to 1.5 mm for MV and 0.9 mm to 1.8 mm for
      kV imagers across the five linacs. The variations in the three calibrations for
      each linac were less than 0.2 mm. Without IsoCal correction, the WL results
      showed discrepancies between the treatment isocenter and the imager center of 0.9
      mm to 1.6 mm (for the MV imager) and 0.5 mm to 1.1 mm (for the kV imager); with
      IsoCal corrections applied, the differences were reduced to 0.2 mm to 0.6 mm (MV)
      and 0.3 mm to 0.6 mm (kV) across the five linacs. The VC system was not as
      precise as the WL system, but showed similar results, with discrepancies of less
      than 1.0 mm when the IsoCal corrections were applied. We conclude that IsoCal is
      an accurate and consistent method for calibration and periodic quality assurance
      of MV and kV imaging systems. 

PMID- 24892343
TI  - Measurement of table feed speed in modern CT.
AB  - The purpose of this study was to develop and evaluate a noninvasive method to
      assess table feed speed (mm/s) in modern commercial computed tomography (CT)
      systems. The table feed (mm/rotation) was measured at selected nominal table feed
      speeds, given as low (26.67 mm/s), intermediate (48.00 mm/s), and high (64.00
      mm/s), by utilizing a computed radiography (CR) cassette installed with a
      photostimulable phosphor plate. The cassette was placed on the examination table
      to travel through the isocenter longitudinally, with a total scan length of over
      430 mm. The distance travelled was employed to determine the total table feed
      length. To calculate the table feed speed, gantry rotation time was measured
      concurrently at a preselected nominal rotation time of 750 ms. Upon completion of
      data acquisition, the table feed and gantry rotation time were analyzed and used
      to calculate the actual table feed speed (mm/s). Under the low table feed speed
      setting, the table feed speed was found to be 26.67 mm/s. Similarly, under the
      intermediate and high table feed speed settings, the table feed speed was found
      to be 48.10 and 64.07 mm/s, respectively. Measurements of the table feed speed
      can be accomplished with a CR system and solid-state detector, and the table feed
      speed results were in excellent agreement with the nominal preset values.

PMID- 24892344
TI  - A Monte Carlo evaluation of beam characteristics for total body irradiation at
      extended treatment distances.
AB  - The aim is to study beam characteristics at large distances when focusing on the
      electron component. In particular, to investigate the utility of spoilers with
      various thicknesses as an electron source, as well as the effect of different
      spoiler-to-surface distances (STSD) on the beam characteristics and,
      consequently, on the dose in the superficial region. A MC model of a 15 MV Varian
      accelerator, validated earlier by experimental data at isocenter and extended
      distances used in large-field total body irradiation, is applied to evaluate beam
      characteristics at distances larger than 400 cm. Calculations are carried out
      using BEAMnrc/DOSXYZnrc code packages and phase space data are analyzed by the
      beam data processor BEAMdp. The electron component of the beam is analyzed at
      isocenter and extended distances, with and without spoilers as beam modifiers,
      assuming vacuum or air surrounding the accelerator head. Spoiler thickness of 1.6
      cm is found to be optimal compared to thicknesses of 0.8 cm and 2.4 cm. The STSD
      variations should be taken into account when treating patients, in particular
      when the treatment protocols are based on a fixed distance to the patient central
      sagittal plane, and also, in order to maintain high dose in the superficial
      region. 

PMID- 24892345
TI  - A respiratory compensating system: design and performance evaluation.
AB  - This study proposes a respiratory compensating system which is mounted on the top
      of the treatment couch for reverse motion, opposite from the direction of the
      targets (diaphragm and hemostatic clip), in order to offset organ displacement
      generated by respiratory motion. Traditionally, in the treatment of cancer
      patients, doctors must increase the field size for radiation therapy of tumors
      because organs move with respiratory motion, which causes radiation-induced
      inflammation on the normal tissues (organ at risk (OAR)) while killing cancer
      cells, and thereby reducing the patient's quality of life. This study uses a
      strain gauge as a respiratory signal capture device to obtain abdomen respiratory
      signals, a proposed respiratory simulation system (RSS) and respiratory
      compensating system to experiment how to offset the organ displacement caused by
      respiratory movement and compensation effect. This study verifies the effect of
      the respiratory compensating system in offsetting the target displacement using
      two methods. The first method uses linac (medical linear accelerator) to
      irradiate a 300 cGy dose on the EBT film (GAFCHROMIC EBT film). The second method
      uses a strain gauge to capture the patients' respiratory signals, while using
      fluoroscopy to observe in vivo targets, such as a diaphragm, to enable the
      respiratory compensating system to offset the displacements of targets in
      superior-inferior (SI) direction. Testing results show that the RSS position
      error is approximately 0.45 ~ 1.42 mm, while the respiratory compensating system
      position error is approximately 0.48 ~ 1.42 mm. From the EBT film profiles based
      on different input to the RSS, the results suggest that when the input
      respiratory signals of RSS are sine wave signals, the average dose (%) in the
      target area is improved by 1.4% ~ 24.4%, and improved in the 95% isodose area by
      15.3% ~ 76.9% after compensation. If the respiratory signals input into the RSS
      respiratory signals are actual human respiratory signals, the average dose (%) in
      the target area is improved by 31.8% ~ 67.7%, and improved in the 95% isodose
      area by 15.3% ~ 86.4% (the above rates of improvements will increase with
      increasing respiratory motion displacement) after compensation. The experimental
      results from the second method suggested that about 67.3% ~ 82.5% displacement
      can be offset. In addition, gamma passing rate after compensation can be improved
      to 100% only when the displacement of the respiratory motion is within 10 ~ 30
      mm. This study proves that the proposed system can contribute to the compensation
      of organ displacement caused by respiratory motion, enabling physicians to use
      lower doses and smaller field sizes in the treatment of tumors of cancer
      patients. 

PMID- 24892347
TI  - Practical considerations in the calibration of CT scanners for proton therapy.
AB  - Treatment planning systems for proton therapy require a CT calibration curve
      relating Hounsfield units to proton stopping powers. An understanding of the
      accuracy of this curve, together with its limitations, is of utmost importance
      because the calibration underpins the calculated dose distribution of every
      patient preparing to undergo proton therapy, independent of delivery technique.
      The most common approach to the calibration is the stoichiometric method, which
      is well-defined and, in principle, straightforward to perform. Nevertheless, care
      must be taken when implementing it in the clinic in order to avoid introducing
      proton range uncertainties into treatment plans that are larger than the 3.5%
      that target margins are typically designed to account for. This work presents a
      variety of aspects related to the user-specific implementation of the
      stoichiometric calibration, from both a measurement setup and a data-handling
      point of view, and evaluates the potential impact of each for treatment planning
      purposes. We demonstrate that two alternative commercial vendors' tissue phantoms
      yield consistent results, that variable CT slice thickness is unimportant, and
      that, for a given cross-sectional size, all phantom data can, with today's state
      of-the-art beam hardening-related artifact reduction software, be acquired
      quickly and easily with a single scan, such that the resulting curve describes
      the calibration well at different positions across the imaging plane. We also
      show that one should be cautious of using metals in the calibration procedure and
      of using a single curve for anatomical sites differing widely in size. Further,
      we suggest that the quality of the parametric fit to the measurement data can be
      improved by performing a constrained, weighted linear regression. These
      observations, based on the 40 separate curves that were calculated, should help
      the medical physicist at any new proton therapy facility in deciding which
      considerations are worth particular attention. 

PMID- 24892346
TI  - Assessment of a quantitative metric for 4D CT artifact evaluation by observer
      consensus.
AB  - The benefits of four-dimensional computed tomography (4D CT) are limited by the
      presence of artifacts that remain difficult to quantify. A correlation-based
      metric previously proposed for cine 4D CT artifact identification was further
      validated as an independent artifact evaluator by using a novel qualitative
      assessment featuring a group of observers reaching a consensus decision on
      artifact location and magnitude. The consensus group evaluated ten cine 4D CT
      scans for artifacts over each breathing phase of coronal lung views assuming one
      artifact per couch location. Each artifact was assigned a magnitude score of 1-5,
      1 indicating lowest severity and 5 indicating highest severity. Consensus group
      results served as the ground truth for assessment of the correlation metric. The
      ten patients were split into two cohorts; cohort 1 generated an artifact
      identification threshold derived from receiver operating characteristic analysis
      using the Youden Index, while cohort 2 generated sensitivity and specificity
      values from application of the artifact threshold. The Pearson correlation
      coefficient was calculated between the correlation metric values and the
      consensus group scores for both cohorts. The average sensitivity and specificity
      values found with application of the artifact threshold were 0.703 and 0.476,
      respectively. The correlation coefficients of artifact magnitudes for cohort 1
      and 2 were 0.80 and 0.61, respectively, (p < 0.001 for both); these correlation
      coefficients included a few scans with only two of the five possible magnitude
      scores. Artifact incidence was associated with breathing phase (p < 0.002), with
      presentation less likely near maximum exhale. Overall, the correlation metric
      allowed accurate and automated artifact identification. The consensus group
      evaluation resulted in efficient qualitative scoring, reduced interobserver
      variation, and provided consistent identification of artifact location and
      magnitudes. 

PMID- 24892348
TI  - Applying the technique of volume-modulated arc radiotherapy to upper esophageal
      carcinoma.
AB  - This study aims to evaluate the possibility of using the technique of volume
      modulated arc therapy (VMAT) to combine the advantages of simplified intensity
      modulated radiation therapy (sIMRT) with that of regular intensity-modulated
      radiation therapy (IMRT) in upper esophageal cancer. Ten patients with upper
      esophageal carcinoma were randomly chosen in this retrospective study. sIMRT,
      IMRT, and VMAT plans were generated to deliver 60 Gy in 30 fractions to the
      planning target volume (PTV). For each patient, with the same clinical
      requirements (target dose prescription, and dose/dose-volume constraints to
      organs at risk (OARs)), three plans were designed for sIMRT (five equispaced
      coplanar beams), IMRT (seven equispaced coplanar beams), and VMAT (two complete
      arcs). Comparisons were performed for dosimetric parameters of PTV and of OARs
      (lungs, spinal cord PRV, heart and normal tissue (NT)). All the plans were
      delivered to a phantom to evaluate the treatment time. The Wilcoxon matched
      pairs, signed-rank test was used for intragroup comparison. For all patients,
      compared to sIMRT plans, VMAT plans statistically provide: a) significant
      improvement in HI and CI for PTV; b) significant decrease in delivery time, lung
      V20, MLD, heart V30 and spinal cord PRV D1cc; c) significant increase in NT V5;
      and d) no significant reduction in lung V5, V10, and heart MD. For all patients,
      compared to IMRT plans, VMAT plans statistically provide: a) significant
      improvement in CI for PTV; b) significant decrease in delivery time, lung V20,
      MLD, NT and spinal cord PRV D1cc; c) significant increase in NT V5; and d) no
      significant reduction in HI for PTV, lung V5, V10, heart V30 and heart MD. For
      patients with upper esophageal carcinoma, using VMAT significantly reduces the
      delivery time and the dose to the lungs compared with IMRT, and consequently
      saves as much treatment time as sIMRT. Considering those significant advantages,
      compared to sIMRT and IMRT, VMAT is the first choice of radiotherapy techniques
      for upper esophageal carcinoma. 

PMID- 24892349
TI  - Evaluation of six TPS algorithms in computing entrance and exit doses.
AB  - Entrance and exit doses are commonly measured in in vivo dosimetry for comparison
      with expected values, usually generated by the treatment planning system (TPS),
      to verify accuracy of treatment delivery. This report aims to evaluate the
      accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV
      beam. The algorithms tested were: pencil beam convolution (Eclipse PBC),
      analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT
      convolution (XiO Convolution), multigrid superposition (XiO Superposition), and
      Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and
      diode detector in water phantoms were used as a reference. Comparisons were done
      in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma
      analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of
      the measured values. Exit doses computed by XiO Convolution, XiO Superposition,
      Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%-3%.
      Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the
      IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume
      that full backscatter exists even at the exit level, leading to an overestimation
      of exit doses. Despite good agreements at the central axis for Eclipse AXB and
      Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond
      11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for
      Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area.
      The findings of this study serve as a useful baseline for the implementation of
      entrance and exit in vivo dosimetry in clinical departments utilizing any of
      these six common TPS algorithms for reference comparison.

PMID- 24892350
TI  - Reproducibility in patient-specific IMRT QA.
AB  - The purpose of this study was to determine the reproducibility of patient
      specific, intensity-modulated radiation therapy (IMRT) quality assurance (QA)
      results in a clinical setting. Six clinical patient plans were delivered to a
      variety of devices and analyses, including 1) radiographic film; 2) ion chamber;
      3) 2D diode array delivered and analyzed in three different configurations (AP
      delivery with field-by-field analysis, AP delivery with composite analysis, and
      planned gantry angle delivery); 4) helical diode array; and 5) in-house-designed
      multiple ion chamber phantom. The six clinical plans were selected from a range
      of treatment sites and were of various levels of complexity. Of note, three of
      the plans had failed at least preliminary evaluation with our in-house IMRT QA;
      the other three plans had passed QA. These plans were delivered three times
      sequentially without changing the setup, and then delivered two more times after
      breaking down and rebuilding the setup between each. This allowed for an
      investigation of reproducibility (in terms of dose, dose difference or percent of
      pixels passing gamma) of both the delivery and the physical setup. This study
      showed that the variability introduced from the setup was generally higher than
      the variability from redelivering the plan. Radiographic film showed the poorest
      reproducibility of the dosimeters investigated. In conclusion, the various IMRT
      QA systems demonstrated varying abilities to reproduce QA results consistently.
      All dosimetric devices demonstrated a reproducibility (coefficient of variation)
      of less than 4% in their QA results for all plans, with an average
      reproducibility of less than 2%. This work provides some quantification for the
      variability that may be seen for IMRT QA dosimeters. 

PMID- 24892351
TI  - An anthropomorphic spine phantom for proton beam approval in NCI-funded trials.
AB  - As part of the approval process for the use of scattered or uniform scanning
      proton therapy in National Cancer Institute (NCI)-sponsored clinical trials, the
      Radiological Physics Center (RPC) mandates irradiation of two RPC anthropomorphic
      proton phantoms (prostate and spine). The RPC evaluates these irradiations to
      ensure that they agree with the institutions' treatment plans within criteria of
      the NCI-funded cooperative study groups. The purpose of this study was to
      evaluate the use of an anthropomorphic spine phantom for proton matched-field
      irradiation, and to assess its use as a credentialing tool for proton therapy
      beams. We used an anthropomorphic spine phantom made of human vertebral bodies
      embedded in a tissue substitute material called Muscle Substitute/Solid Rigid
      Number 4 (MS/SR4) comprising three sections: a posterior section containing the
      posterior surface and the spinous processes, and left and right (L/R) sections
      containing the vertebral bodies and the transverse processes. After feasibility
      studies at three institutions, the phantom, containing two thermoluminescent
      dosimeters (TLDs) for absolute dose measurements and two sheets of radiochromic
      film for relative dosimetry, was shipped consecutively to eight proton therapy
      centers participating in the approval study. At each center, the phantom was
      placed in a supine or prone position (according to the institution's spine
      treatment protocol) and imaged with computed tomography (CT). The images then
      were used with the institution's treatment planning system (TPS) to generate two
      matched fields, and the phantom was irradiated accordingly. The irradiated
      phantom was shipped to the RPC for analysis, and the measured values were
      compared with the institution's TPS dose and profiles using criteria of +/- 7%
      for dose agreement and 5 mm for profile distance to agreement. All proton centers
      passed the dose criterion with a mean agreement of 3% (maximum observed
      agreement, 7%). One center failed the profile distance-to-agreement criterion on
      its initial irradiation, but its second irradiation passed the criterion. Another
      center failed the profile distance-to-agreement criterion, but no repeat
      irradiation was performed. Thus, seven of the eight institutions passed the film
      profile distance-to-agreement criterion with a mean agreement of 1.2 mm (maximum
      observed agreement 5 mm). We conclude that an anthropomorphic spine phantom using
      TLD and radiochromic film adequately verified dose delivery and field placement
      for matched-field treatments. 

PMID- 24892352
TI  - Implementation of an improved dose-per-MU model for double-scattered proton beams
      to address interbeamline modulation width variability.
AB  - Because treatment planning systems (TPSs) generally do not provide monitor units
      (MUs) for double-scattered proton plans, models to predict MUs as a function of
      the range and the nominal modulation width requested of the beam delivery system,
      such as the one developed by the MGH group, have been proposed. For a given
      nominal modulation width, however, the measured modulation width depends on the
      accuracy of the vendor's calibration process and may differ from this nominal
      value, and also from one beamline to the next. Although such a difference can be
      replicated in our TPS, the output dependence on range and modulation width for
      each beam option or suboption has to be modeled separately for each beamline in
      order to achieve maximal 3% inaccuracy. As a consequence, the MGH output model
      may not be directly transferable. This work, therefore, serves to extend the
      model to more general clinic situations. In this paper, a parameterized linear
      quadratic transformation is introduced to convert the nominal modulation width to
      the measured modulation width for each beam option or suboption on a per-beamline
      basis. Fit parameters are derived for each beamline from measurements of 60
      reference beams spanning the minimum and maximum ranges, and modulation widths
      from 2 cm to full range per option or suboption. Using the modeled modulation
      width, we extract the MGH parameters for the output dependence on range and
      modulation width. Our method has been tested with 1784 patient-specific fields
      delivered across three different beamlines at our facility. For these fields, all
      measured outputs fall within 3%, and 64.4% fall within 1%, of our model. Using a
      parameterized linear-quadratic modulation width, MU calculation models can be
      established on a per-beamline basis for each double scattering beam option or
      suboption. 

PMID- 24892353
TI  - Four-and-one-half years' experience in monitoring of reproducibility of an MR
      spectroscopy system--application of in vitro results to interpretation of in vivo
      data.
AB  - The primary purpose of this work was to assess long-term in vitro reproducibility
      of metabolite levels measured using 1H MRS (proton magnetic resonance
      spectroscopy). The secondary purpose was to use the in vitro results for
      interpretation of 1H MRS in vivo spectra acquired from patients diagnosed with
      Canavan disease. 1H MRS measurements were performed in the period from April 2006
      to September 2010. 118 short and 116 long echo spectra were acquired from a
      stable phantom during this period. Change-point analysis of the in vitro N
      acetylaspartate levels was exploited in the computation of fT factor (ratio of
      the actual to the reference N-acetylaspartate level normalized by the reciprocity
      principle). This coefficient was utilized in the interpretation of in vivo
      spectra analyzed using absolute reference technique. The monitored time period
      was divided into six time intervals based on short echo in vitro data (seven time
      intervals based on long echo in vitro data) characterized by fT coefficient
      ranging from 0.97 to 1.09 (based on short echo data) and from 1.0 to 1.11 (based
      on long echo data). Application of this coefficient to interpretation of in vivo
      spectra confirmed increased N-acetylaspartate level in Canavan disease. Long-term
      monitoring of an MRS system reproducibility, allowing for absolute referencing of
      metabolite levels, facilitates interpretation of metabolic changes in white
      matter disorders.

PMID- 24892354
TI  - Essentials and guidelines for clinical medical physics residency training
      programs: executive summary of AAPM Report Number 249.
AB  - There is a clear need for established standards for medical physics residency
      training. The complexity of techniques in imaging, nuclear medicine, and
      radiation oncology continues to increase with each passing year. It is therefore
      imperative that training requirements and competencies are routinely reviewed and
      updated to reflect the changing environment in hospitals and clinics across the
      country. In 2010, the AAPM Work Group on Periodic Review of Medical Physics
      Residency Training was formed and charged with updating AAPM Report Number 90.
      This work group includes AAPM members with extensive experience in clinical,
      professional, and educational aspects of medical physics. The resulting report,
      AAPM Report Number 249, concentrates on the clinical and professional knowledge
      needed to function independently as a practicing medical physicist in the areas
      of radiation oncology, imaging, and nuclear medicine, and constitutes a revision
      to AAPM Report Number 90. This manuscript presents an executive summary of AAPM
      Report Number 249. 

PMID- 24892355
TI  - In-house development of a neonatal chest simulation phantom.
AB  - The aim of the study was to design and construct an anatomical and radiological
      phantom of a neonatal chest for investigating image quality and patient entrance
      surface dose (ESD). The density, elemental composition, scatter, attenuation, and
      absorption characteristics of different possible substitute materials were
      compared to that of neonatal tissues for radiological equivalence. Availability
      and cost of possible substitute materials were also considered. The most optimal
      substitute materials were selected to represent neonatal muscle, bone, healthy or
      aerated and sick or collapsed lung. For anatomical equivalence, a computed
      tomography (CT) scan was performed on a neonatal cadaver. Dimensions of different
      organs and structures were measured with software measuring tools at different
      window and level settings. Simplifying assumptions, due to machining limitations,
      were made. The results were used to create scaled drawings, which were used to
      machine the structures of the phantom. The phantom was assembled in a layer-by
      layer manner and was validated with region of interest (ROI) analyses. The
      neonatal chest simulation phantom was an acceptable simulation of a real neonatal
      chest based on ROI validation, with an overall deviation of 32.5%. The phantom
      was successfully used in our diagnostic radiology division for ESD and image
      quality investigations for chest anterior-posterior (AP) radiographs. 

PMID- 24892357
TI  - The meaning of the MS degree in medical physics, part 3.

PMID- 24892359
TI  - Identification of a novel HIV-1 second-generation recombinant form
      (CRF01_AE/CRF07_BC) in Jilin, China.
AB  - We report here a novel HIV-1 second-generation recombinant form
      (CRF01_AE/CRF07_BC) isolated from an HIV-positive male subject infected through
      heterosexual contact in Jilin province in northeastern China. Phylogenic analysis
      shows that this novel second-generation recombinant (JL.RF09) was composed of two
      well-established circulating recombinant forms (CRF01_AE and CRF07_BC), with two
      recombinant breakpoints observed in the vpu/env and env gene regions,
      respectively. The CRF01_AE region of the recombinant was clustered together with
      a previously described subcluster 4a lineage of CRF01_AE, which is exclusively
      circulating among men who have sex with men (MSM) in northern China, indicating
      that the parental origin of the CRF01_AE region in JL.RF09 was from MSM in north
      China. The CRF07_BC regions of the recombinant are clustered within the CRF07_BC
      cluster but are distinct from other CRF07_BC references. The detailed origin of
      CRF07_BC in this recombinant is still not clear. The emergence of the novel HIV-1
      recombinant indicates the ongoing generation of recombinants involving CRF01_AE
      and CRF07_BC, and may provide vital insights into our understanding of the
      dynamics and complexity of the HIV-1 epidemic in China.

PMID- 24892360
TI  - Breastfeeding during pregnancy: safety and socioeconomic status.

PMID- 24892361
TI  - Hypoglycemia-related electroencephalogram changes assessed by multiscale entropy.
AB  - BACKGROUND: Several clinical studies have shown that low blood glucose (BG)
      levels affect electroencephalogram (EEG) rhythms through the quantification of
      traditional indicators based on linear spectral analysis. Nonlinear measures used
      in the last decades to characterize the EEG in several physiopathological
      conditions have never been assessed in hypoglycemia. The present study
      investigates if properties of the EEG signal measured by nonlinear entropy-based
      algorithms are altered in a significant manner when a state of hypoglycemia is
      entered. SUBJECTS AND METHODS: EEG was acquired from 19 patients with type 1
      diabetes during a hyperinsulinemic-euglycemic-hypoglycemic clamp experiment. In
      parallel, BG was frequently monitored by the standard YSI glucose and lactate
      analyzer and used to identify two 1-h intervals corresponding to euglycemia and
      hypoglycemia, respectively. In each subject, the P3-C3 EEG derivation in the two
      glycemic intervals was assessed using the multiscale entropy (MSE) approach,
      obtaining measures of sample entropy (SampEn) at various temporal scales. The
      comparison of how signal irregularity measured by SampEn varies as the temporal
      scale increases in the two glycemic states provides information on how EEG
      complexity is affected by hypoglycemia. RESULTS: For both glycemic states, the
      MSE analysis showed that SampEn increases at small time scales and then
      monotonically decreases as the time scale becomes larger. Comparing the two
      conditions, SampEn was higher in hypoglycemia only at medium time scales.
      CONCLUSIONS: A decrease in the complexity of EEG occurs when a state of
      hypoglycemia is entered, because of a degradation of the EEG long-range temporal
      correlations. Thanks to its ability to assess nonlinear dynamics of the EEG
      signal, the MSE approach seems to be a useful tool to complement information
      brought by standard linear indicators and provide new insights on how
      hypoglycemia affects brain functioning.

PMID- 24892362
TI  - Phenolic extract of Dialium guineense pulp enhances reactive oxygen species
      detoxification in aflatoxin B1 hepatocarcinogenesis.
AB  - This study investigated the effect of Dialium guineense pulp phenolic extract on
      aflatoxin B1 (AFB1)-induced oxidative imbalance in rat liver. Reactive oxygen
      species (ROS) scavenging potentials of free and bound phenolic extract of D.
      guineense (0.2-1.0 mg/mL) were investigated in vitro using 2,2-diphenyl-1
      picrylhydrazyl (DPPH) radical, superoxide ion (O2(-)), hydrogen peroxide (H2O2),
      hydroxyl radical, and ferric ion reducing system. In the in vivo study, 35
      animals were randomized into seven groups of five rats each. Free and bound
      phenolic extract (1 mg/mL) produced 66.42% and 93.08%, 57.1% and 86.0%, 62.0% and
      90.05%, and 60.11% and 72.37% scavenging effect on DPPH radical, O2(-) radical,
      H2O2, and hydroxyl radical, while ferric ion was significantly reduced. An AFB1
      mediated decrease in the activities of ROS detoxifying enzymes (superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose 6
      phosphate dehydrogenase) was significantly attenuated (P<.05). AFB1-mediated
      elevation in the concentrations of oxidative stress biomarkers; malondialdehyde,
      conjugated dienes, lipid hydroperoxides, protein carbonyl, and percentage DNA
      fragmentation were significantly lowered by D. guineense phenolic extract
      (P<.05). Overall, the in vitro and in vivo effects suggest that D. guineense
      phenolic extract elicited ROS scavenging and detoxification potentials, as well
      as the capability of preventing lipid peroxidation, protein oxidation, and DNA
      fragmentation.

PMID- 24892363
TI  - A prospective, multi-centered study of the treatment of idiopathic sudden
      sensorineural hearing loss with combination therapy versus high-dose prednisone
      alone: a 139 patient follow-up.
AB  - OBJECTIVE: To compare combination therapy (high-dose prednisone taper (HDPT) +
      intratympanic dexamethasone (IT-Dex)) hearing recovery results in ISSNHL patients
      with those treated with HDPT alone. DESIGN: Prospective, multicentered trial.
      SETTING: Tertiary referral center. PATIENTS: Eighty ISSNHL patients with class C
      or D hearing. INTERVENTION: Eighty qualifying patients were treated with IT-Dex
      (10 mg/ml) every week for 3 weeks concomitant with HDPT (60 mg/d for 7 d with 7-d
      taper) and followed prospectively. MAIN OUTCOME MEASURE(S): Four-tone pure tone
      average (PTA) at 0.25, 0.5, 1, and 2 kHz and speech discrimination scores (SDS) 2
      months posttreatment; Hearing results compared retrospectively with those of 59
      ISSNHL treated with HDPT alone. RESULTS: Combination therapy and HDPT alone both
      provided a statistically significant benefit in audiometric parameters,
      especially if treated within 7 days of onset. However, 49% versus 29% (p = 0.02)
      of class D patients receiving combination therapy versus HDPT achieved
      serviceable hearing. Patients receiving combination therapy versus HDPT
      experienced a significantly greater improvement in PTA (34.1 +/- 27 dB versus
      12.0 +/- 21 dB; p < 0.0001) and SDS (49.9.2 +/- 38% versus 19.2 +/- 36%; p <
      0.0001) while achieving a significantly better final PTA (50.6 +/- 28 dB versus
      65.5 +/- 29 dB; p = 0.005) and SDS (62.4 +/- 40% versus 44.7 +/- 41%; p = 0.01).
      Approximately 56% of class D and 40% of profound patients treated within 7 days
      with combination therapy achieved serviceable hearing. CONCLUSION: Combination
      therapy offers ISSNHL patients the highest likelihood of achieving class A and B
      hearing. Differential results with combination therapy and HDPT compared with
      previous studies suggest time- and dose-dependent responses to the treatment of
      ISSNHL.

PMID- 24892364
TI  - A comparison of preoperative characteristics of chronic otitis media in Down and
      non-Down syndrome.
AB  - OBJECTIVE: To investigate preoperative clinical findings of chronic otitis media
      (COM) in patients with Down and without (non-Down) syndrome. STUDY DESIGN:
      Retrospective. SETTING: Referral hospital, otolaryngology department. PATIENTS:
      Patients with COM who underwent tympanoplasty were included. There were 10 ears
      of 8 patients (mean age, 14.9 yr) in the Down group and 44 ears of 41 patients
      (mean age, 14.7 yr) in the non-Down group. MAIN OUTCOME MEASURES: Clinical
      characteristics, including the frequency of preoperative persistent otorrhea,
      cause of COM, and mastoid pneumatization (maturation), were compared between the
      2 groups using clinical records and temporal bone computed tomography (CT).
      RESULTS: Preoperative persistent otorrhea was more frequent in the Down group
      (60%) than in the non-Down group (27.2%; p < 0.05). Perforation due to
      tympanostomy tube insertion also occurred more frequently in the Down group
      (100%) than in the non-Down group (53.3%; p < 0.05). Mastoid pneumatization
      occurred significantly less in the Down group than in the non-Down group (p <
      0.01). There was no significant difference in mastoid pneumatization regardless
      of the presence or absence of a past history of tympanostomy tube insertion in
      the Down group (p = 0.3, t test) unlike that in the non-Down group (p < 0.05, t
      test). All ears attained a dry condition with no perforated eardrums. CONCLUSION:
      Frequent draining ear and extremely immature mastoid pneumatization, regardless
      of the presence or absence of a past history of tympanostomy tube insertion, were
      clinically important characteristics of COM in patients with Down syndrome.

PMID- 24892366
TI  - Utility of MRIs in adult cochlear implant evaluations.
AB  - OBJECTIVES: To determine the prevalence of MRI abnormalities in adults undergoing
      cochlear implantation and to correlate abnormalities to audiology data. STUDY
      DESIGN: Case series. SETTING: Academic medical center. METHODS: Adult patients
      (>18 yr old) undergoing cochlear implant evaluation from January 2008 to December
      2012 were identified based on CPT code search. Demographics, preoperative MRI
      findings, operative findings, and audiometric data were collected. RESULTS: The
      study included 188 patients. Seventeen (9%) patients had significant otic capsule
      or vestibulocochlear nerve pathologies: 5 vestibular schwannomas, 4 enlarged
      vestibular aqueducts, 2 hypoplastic cochlear nerves, 2 labyrinthitis ossificans,
      1 cochlear aplasia, 1 posterior semicircular canal malformation, 1 calcified
      meningioma, and 1 cholesterol granuloma. MRI results were normal (65%) or with
      findings not directly related to hearing loss (incidental findings, 25%) in the
      remaining patients. Mean pure tone average (PTA) differences (between the
      implanted and contralateral ear) did not significantly vary between normal
      incidental and abnormal MRI scans (-6.6 dB versus -6.7 dB, p = 0.99) nor did
      speech discrimination scores (SDS) scores (8.5% versus 8.4%, p = 0.99). No
      significant difference was found in HINT scores for patients with a normal versus
      an abnormal MRI (19% versus 16,%, p = 0.62). CONCLUSION: Although the majority of
      precochlear implantation MRIs were normal or demonstrated incidental findings,
      such as white matter changes, significant MRI findings affecting implantation
      site and patient counseling were found in almost 10% of patients. Audiogram
      findings did not correlate with abnormal findings on MRIs. Routine use of MRI in
      adult cochlear implant candidates may be warranted.

PMID- 24892365
TI  - Vocalization-induced stapedius contraction.
AB  - OBJECTIVE: To present a case of a patient with visible stapedius contraction on
      vocalization and to discuss the related literature. PATIENTS: A 51 year-old woman
      with a Type III myringostapediopexy due to chronic suppurative otitis media and
      an incidental finding of voice-induced movement of the stapes head.
      INTERVENTIONS: Otoendoscopy, pure tone and impedance audiometry, and modified
      stapedius reflex decay. MAIN OUTCOME MEASURE: Stapes head movement on
      otoendoscopy. RESULTS: Stapes head movement was seen endoscopically on
      vocalization but not on tympanometric measures. CONCLUSION: Visible stapedius
      contraction with vocalization is an uncommon phenomenon. Our understanding of the
      nonauditory pathways to stapedius is limited and requires further research.

PMID- 24892367
TI  - Idiopathic oculostapedial synkinesis without history of facial nerve palsy.
AB  - OBJECTIVE: To report a case of idiopathic oculostapedial synkinesis without
      facial nerve disorder. PATIENT: A 30-year-old woman with tinnitus synchronous
      with eye closure is presented. The patient had no history of facial nerve
      disorder. RESULT: An impedance audiometer, in the absence of an auditory
      stimulus, was used to record tympanic membrane compliance without sound
      stimulation, revealing decreased compliance in the concomitant with eye blinking.
      Her symptoms disappeared spontaneously, so no intervention was undertaken.
      CONCLUSION: Although oculostapedial synkinesis is often observed as one of the
      sequelae of facial nerve palsy, idiopathic oculostapedial synkinesis is very
      rare. The use of an impedance audiometer in the absence of an auditory stimulus
      is very useful for demonstrating objective changes in the compliance of the
      tympanic membrane. It is assumed that the cause of the synkinesis in our case was
      abnormal transmission of signals for orbicularis oculi muscle to the stapedial
      and orbicularis oris muscles rather than misdirected regenerating fibers.
      Resection of the stapedial muscle tendon should be considered if her symptoms
      recur.

PMID- 24892368
TI  - A longitudinal study of hearing and middle ear status in individuals with UCLP.
AB  - OBJECTIVE: To define the age when the higher prevalence of abnormal middle ear
      dissipates in individuals with cleft lip and palate and to investigate how this
      may affect hearing sensitivity over time. STUDY DESIGN: Retrospective and
      prospective cohort study. SETTING: University hospital. PATIENTS: Three groups of
      individuals with unilateral cleft lip and palate from the same cleft center: 1) a
      group of individuals followed longitudinally from 1 to 5 years of age (n = 22),
      2) another group of individuals followed longitudinally from 7 to 16 years of age
      (n = 24), and 3) a group which encompasses young adults between 20 and 31 years
      of age (n = 26). MAIN OUTCOMES MEASURE(S): Abnormal middle ear status and hearing
      sensitivity. RESULTS: The prevalence of abnormal middle ear status decreases as
      the individuals within the 3 groups age from 89% at age 1 year to 10% in young
      adulthood. Hearing statistically improved as children became older up to 13 years
      of age and then worsened in the high frequencies between 16 and 20 to 31 years of
      age. CONCLUSION: There is a high prevalence of abnormal middle ear status in
      individuals with cleft lip and palate. This higher prevalence of abnormal middle
      ear status may lead to poorer high-frequency hearing, which could potentially
      lead to challenges in academics and difficulties understanding speech in social
      situations. Further investigation into these, the prevalence of abnormal middle
      ear status and hearing in comparison to a control group is warranted.

PMID- 24892369
TI  - Intracochlear electrocochleography during cochlear implantation.
AB  - OBJECTIVE: Electrophysiologic responses to acoustic stimuli are present in nearly
      all cochlear implant recipients when measured at the round window (RW).
      Intracochlear recording sites might provide an even larger signal and improve the
      sensitivity and the potential clinical utility of electrocochleography (ECoG).
      Thus, the goal of this study is to compare RW to intracochlear recording sites
      and to determine if such recordings can be used to monitor cochlear function
      during insertion of a cochlear implant. METHODS: Intraoperative ECoG recordings
      were obtained in subjects receiving a cochlear implant from the RW and from just
      inside scala tympani (n = 26). Stimuli were tones at high levels (80-100 dB HL).
      Further recordings were obtained during insertions of a temporary lateral
      cochlear wall electrode (n = 8). Response magnitudes were determined as the sum
      of the first and second harmonics amplitudes. RESULTS: All subjects had
      measurable extracochlear responses at the RW. Twenty cases (78%) showed a larger
      intracochlear response, compared with three (11%) that had a smaller response and
      three that were unchanged. On average, signal amplitudes increased with
      increasing electrode insertion depths, with the largest increase between 15 and
      20 mm from the RW. CONCLUSION: ECoG to acoustic stimuli via an intracochlear
      electrode is feasible in standard cochlear implant recipients. The increased
      signal can improve the speed and efficiency of data collection. The growth of
      response magnitudes with deeper intrascalar electrode positions could be
      explained by closer proximity or favorable geometry with respect to residual
      apical signal generators. Reductions in magnitude may represent unfavorable
      geometry or cochlear trauma.

PMID- 24892370
TI  - Ex vivo visualization of the mouse otoconial layer compared with micro-computed
      tomography.
AB  - HYPOTHESIS: Micro-computed tomography (micro-CT) is useful for assessing the 3
      dimensional (3D) morphology and age-related changes of the otoconial layer.
      BACKGROUND: Wriggle mouse Sagami (WMS) is a mutant of the plasma membrane Ca2+
      ATPase type2 gene (Atp2b2) with deficits in the saccular otoconia. We examined
      the effectiveness of micro-CT in evaluating the otoconial layer of WMS and
      C57BL/6J mice. METHODS: Otic capsules of C57BL/6J mice at different fixation time
      were examined using micro-CT to evaluate the effects of the fixation time on the
      otoconial layer. Otic capsules of Atp2b2(wri/wri), Atp2b2(wri/+), and Atp2b2(+/+)
      mice at P14, P21, and the age of 3 months were used to analyze age-related
      changes in the otoconial layer. A series of cross-section and 3D reconstructed
      images of the otoconial layer were obtained. The micro-CT findings were compared
      with the otic capsule findings cleared in methyl salicylate using
      stereomicroscopy. RESULTS: Micro-CT produced high-resolution images of the
      otoconial layer, thereby providing information regarding the spatial
      configuration and 3D curvature. There were no changes between the different
      fixation times. In the Atp2b2(wri/+) and Atp2b2(+/+) mice, the saccular and
      utricular otoconial layers were normal among all age groups. In the
      Atp2b2(wri/wri) mice, the saccular otoconial layer decreased on P14 and was
      absent on P21, whereas the utricular otoconial layer disappeared at 3 months of
      age. CONCLUSION: We obtained precise information regarding the mouse otoconial
      layer with minimum artifacts. This method is expected to improve our
      understanding of the physiologic function and age-related changes in otolith
      organs.

PMID- 24892371
TI  - Eosinophilic otitis media.

PMID- 24892372
TI  - Endoscopic view of the scala tympani.

PMID- 24892373
TI  - Hilary Koprowski and the viral immunity hub at the 1980s Wistar Institute: a T
      cell epitope perspective.

PMID- 24892375
TI  - Hydrophilic, bright CuInS2 quantum dots as Cd-free fluorescent labels in
      quantitative immunoassay.
AB  - We report on the synthesis of core-shell CuInS2/ZnS quantum dots (QDs) in organic
      solution, their encapsulation with a PEG-containing amphiphilic polymer, and the
      application of the resulting water-soluble QDs as fluorescent label in
      quantitative immunoassay. By optimizing the methods for core synthesis and shell
      growth, CuInS2/ZnS QDs were obtained with a quantum yield of 50% on average after
      hydrophilization. After conjugation with an aflatoxin B1-protein derivative, the
      obtained QDs were used as fluorescent labels in microplate immunoassay for the
      quantitative determination of the mycotoxin aflatoxin B1. QDs-based immunoassay
      showed higher sensitivity compared to enzyme-based immunoassay. 

PMID- 24892376
TI  - Role of intrafibrillar collagen mineralization in defining the compressive
      properties of nascent bone.
AB  - Bone is the sole biological material found in the human body that is able to
      sustain compressive loads. However, although the structure of bone is well-known
      (it is a natural composite of collagen protein and hydroxyapatite mineral with a
      complex hierarchical organization), the details about the mechanisms that govern
      deformation at the molecular scale under compressive loading are still not
      completely understood. To investigate the molecular origins of bone's unique
      compressive properties, we perform full atomistic simulations of the three
      dimensional molecular structure of a mineralized collagen fibril, focusing on the
      role of intrafibrillar mineral densities in dictating the mechanical performance
      under compressive loading. We find that as the mineral density increases, the
      compressive modulus of the mineralized collagen increases monotonically and well
      beyond that of pure collagen fibrils. These findings reveal the mechanism by
      which bone is able to achieve superior load bearing characteristics beyond its
      individual constituents. Moreover, we find that intrafibrillar mineralization
      leads to compressive moduli that are one order of magnitude lower than the
      macroscale modulus of bone, indicating that extrafibrillar mineralization is
      mandatory for providing the load bearing properties of bone, consistent with
      recent experimental observations. 

PMID- 24892377
TI  - Femtosecond laser-assisted astigmatic keratotomy for postoperative trabeculectomy
      induced corneal astigmatism.
AB  - PURPOSE: To describe a case of postoperative trabeculectomy-induced corneal
      astigmatism treated with femtosecond laser-assisted astigmatic keratotomy.
      METHODS: After trabeculectomy, the patient demonstrated change in manifest
      refraction from -0.5 diopters preoperatively to mixed astigmatism of -3.5 +
      5.25@100 postoperatively and a decrease in uncorrected distance visual acuity
      from 20/60 preoperatively to 20/200 at 1 month postoperatively. Because the
      patient was intolerant to spectacle use, she underwent femtosecond laser-assisted
      astigmatic keratotomy. RESULTS: After astigmatic keratotomy there was improvement
      in corneal topographic astigmatism from 4.15 to 0.81 diopters with uncorrected
      distance visual acuity of 20/60(-2) and manifest refraction of -0.75 + 1.0@90 at
      3 months postoperatively. There were no intraoperative or postoperative
      complications. CONCLUSIONS: Femtosecond laser-assisted astigmatic keratotomy may
      be considered in eyes with postoperative trabeculectomy-induced mixed
      astigmatism.

PMID- 24892374
TI  - Early life nutrition, epigenetics and programming of later life disease.
AB  - The global pandemic of obesity and type 2 diabetes is often causally linked to
      marked changes in diet and lifestyle; namely marked increases in dietary intakes
      of high energy diets and concomitant reductions in physical activity levels.
      However, less attention has been paid to the role of developmental plasticity and
      alterations in phenotypic outcomes resulting from altered environmental
      conditions during the early life period. Human and experimental animal studies
      have highlighted the link between alterations in the early life environment and
      increased risk of obesity and metabolic disorders in later life. This link is
      conceptualised as the developmental programming hypothesis whereby environmental
      influences during critical periods of developmental plasticity can elicit
      lifelong effects on the health and well-being of the offspring. In particular,
      the nutritional environment in which the fetus or infant develops influences the
      risk of metabolic disorders in offspring. The late onset of such diseases in
      response to earlier transient experiences has led to the suggestion that
      developmental programming may have an epigenetic component, as epigenetic marks
      such as DNA methylation or histone tail modifications could provide a persistent
      memory of earlier nutritional states. Moreover, evidence exists, at least from
      animal models, that such epigenetic programming should be viewed as a
      transgenerational phenomenon. However, the mechanisms by which early
      environmental insults can have long-term effects on offspring are relatively
      unclear. Thus far, these mechanisms include permanent structural changes to the
      organ caused by suboptimal levels of an important factor during a critical
      developmental period, changes in gene expression caused by epigenetic
      modifications (including DNA methylation, histone modification, and microRNA) and
      permanent changes in cellular ageing. A better understanding of the epigenetic
      basis of developmental programming and how these effects may be transmitted
      across generations is essential for the implementation of initiatives aimed at
      curbing the current obesity and diabetes crisis. 

PMID- 24892378
TI  - Corneal collagen cross-linking for Terrien marginal degeneration.
AB  - PURPOSE: To report the long-term clinical outcome of a patient diagnosed as
      having Terrien marginal degeneration (TMD) who was subjected to corneal collagen
      cross-linking (CXL) with ultraviolet-A and riboflavin in both eyes. METHODS:
      Topographical changes were assessed by high-resolution Scheimpflug imaging and
      anterior segment optical coherence tomography. Eccentric epithelium-off CXL was
      performed in both eyes while protecting the corneal limbus. Irradiation was
      performed with a fluence of 5.4 J/cm(2), using 3 mW/cm(2) for 30 minutes.
      RESULTS: Five years of postoperative follow-up showed regression of the
      keratometric values, a local thickening of the corneal stroma, and bilateral
      improvement of corrected distance visual acuity. CONCLUSIONS: CXL may arrest
      progression in TMD and even reverse the catabolic process in the corneal stroma.
      CXL might represent an alternative therapeutic approach for the management of
      TMD.

PMID- 24892379
TI  - Corneal cross-linking for treatment of progressive keratoconus in various age
      groups.
AB  - PURPOSE: To compare the effect of corneal cross-linking (CXL) for keratoconus in
      various age groups and to investigate the influence of the topographic cone
      location on the outcome of CXL. METHODS: This cohort study included 95 patients
      (119 eyes) diagnosed as having progressive keratoconus who underwent epithelium
      off standard protocol CXL from January 2010 through May 2012. For statistical
      analysis, patients were divided into three age groups: pediatric patients (< 18
      years), adolescent patients (18 to 26 years), and adults (> 26 years). Visual
      acuity and refraction, topography, intraocular pressure, and endothelial cell
      counts were recorded preoperatively and postoperatively. RESULTS: Topographic
      cones were located more centrally in pediatric corneas (0.85 +/- 0.66 mm)
      compared to adolescent corneas (1.49 +/- 0.76 mm, P = .002) and adult corneas
      (1.86 +/- 0.99 mm, P < .001). Pediatric corneas flattened 1 year after CXL by a
      mean of 1.8 diopters (D), compared to 1.1 D in the other age groups. Central
      cones (0 to 1 mm) were steeper (62.3 +/- 8.3 D) before treatment than peripheral
      cones (3 to 4 mm) (55.9 +/- 8.9 D). One year after CXL, corrected distance visual
      acuity improved in all age groups, with the highest improvement in pediatric eyes
      (-0.23 +/- 0.40 logMAR, P = .044). CONCLUSIONS: Before CXL, cones of pediatric
      keratoconic corneas were located more centrally than in the two older age groups.
      After CXL, pediatric corneas showed more corneal flattening and more corrected
      distance visual acuity improvement. Pediatric CXL was equally safe compared to
      adolescent and adult CXL.

PMID- 24892380
TI  - Modified technique for combining DMEK with glued intrascleral haptic fixation of
      a posterior chamber IOL as a single-stage procedure.
AB  - PURPOSE: To describe changes in the surgical technique required for combining
      Descemet membrane endothelial keratoplasty with glued intrascleral haptic
      fixation of a posterior chamber intraocular lens ([IOL] glued IOL) as a single
      stage surgery in patients diagnosed as having aphakic or pseudophakic bullous
      keratopathy. METHODS: Six patients with corneal decompensation and inadequate
      capsular support requiring implantation/exchange of an IOL underwent a single
      staged glued IOL with Descemet membrane endothelial keratoplasty at a tertiary
      care center. Stability of the anterior chamber and structure of iris diaphragm
      IOL complex were assessed intraoperatively by injecting air and, when required,
      iridoplasty was performed. Patients were observed postoperatively. RESULTS: One
      patient had partial graft detachment requiring re-bubbling and 1 patient had a
      small peripheral detachment with spontaneous resolution. The graft remained
      attached in all patients. An iridoplasty was required for 2 patients. Visual
      acuity improved in all patients. The mean preoperative and postoperative
      corrected distance visual acuity were 0.11 +/- 0.07 and 0.7 +/- 0.17,
      respectively. There was significant change in the corrected distance visual
      acuity after surgery (P = .028). The mean postoperative endothelial cell density
      at 6 months was 1,710.3 +/- 205.8 cells/mm(2). CONCLUSIONS: Descemet membrane
      endothelial keratoplasty with glued IOL provides stable IOL with decreased
      pseudophacodonesis for better graft fixation. Iris diaphragm covering IOL optic
      all around is essential to restore bicamerality, allows sufficiently sized, non
      migrating air bubbles, and decreases graft detachment and dislocation both
      intraoperatively and postoperatively. A need for iridoplasty must be confirmed
      intra-operatively.

PMID- 24892381
TI  - Reduction of hydroxylated fullerene (fullerol) in water by zinc: reaction and
      hemiketal product characterization.
AB  - Water-soluble, hydroxylated fullerene (fullerol) materials have recently gained
      increasing attention as they have been identified as the primary product(s)
      during the exposure of fullerenes (as water stable, nanoscale aggregated C60) to
      UV light in water. The physical properties and chemical reactivity of resulting
      fullerols, however, have not been thoroughly studied. In this paper, we
      identified and characterized the reductive transformation of fullerol
      (C60(OH)x(ONa)y) by solid zinc metal (Zn(0)) through a series of batch reaction
      experiments and product characterization, including (13)C NMR, FTIR, XPS, UV-vis,
      DLS, and TEM. Results indicated the facile formation of water stable, pH
      sensitive hemiketal functionality as part of a relatively reduced fullerol
      product. Further, aqueous physical behavior of the product fullerol, as measured
      by octanol partitioning and surface deposition rates, was observed to
      significantly differ from the parent material and is consistent with a relative
      increase in molecular (product) hydrophobicity. 

PMID- 24892382
TI  - Continuous-flow microelectroextraction for enrichment of low abundant compounds.
AB  - We present a continuous-flow microelectroextraction flow cell that allows for
      electric field enhanced extraction of analytes from a large volume (1 mL) of
      continuously flowing donor phase into a micro volume of stagnant acceptor phase
      (13.4 MUL). We demonstrate for the first time that the interface between the
      stagnant acceptor phase and fast-flowing donor phase can be stabilized by a
      phaseguide. Chip performance was assessed by visual experiments using crystal
      violet. Then, extraction of a mixture of acylcarnitines was assessed by off-line
      coupling to reversed phase liquid chromatography coupled to time-of-flight mass
      spectrometry, resulting in concentration factors of 80.0 +/- 9.2 times for
      hexanoylcarnitine, 73.8 +/- 9.1 for octanoylcarnitine, and 34.1 +/- 4.7 times for
      lauroylcarnitine, corresponding to recoveries of 107.8 +/- 12.3%, 98.9 +/- 12.3%,
      and 45.7 +/- 6.3%, respectively, in a sample of 500 MUL delivered at a flow of 50
      MUL min(-1) under an extraction voltage of 300 V. Finally, the method was applied
      to the analysis of acylcarnitines spiked to urine, resulting in detection limits
      as low as 0.3-2 nM. Several putative endogenous acylcarnitines were found. The
      current flowing-to-stagnant phase microelectroextraction setup allows for the
      extraction of milliliter range volumes and is, as a consequence, very suited for
      analysis of low-abundant metabolites. 

PMID- 24892383
TI  - Effects of Ga:N addition on the electrical performance of zinc tin oxide thin
      film transistor by solution-processing.
AB  - This paper addressed the effect of gallium nitrate hydrate addition on thin film
      transistor (TFT) performance and positive bias stability of amorphous zinc tin
      oxide (ZTO) TFTs by solution processing, Further, the mechanisms responsible for
      chemical properties and electronic band structure are explored. A broad
      exothermic peak accompanied by weight loss appeared in the range from about 350
      to 570  degrees C for the ZTO solution; the thermal reaction of the Ga-ZTO:N
      solution was completed at 520  degrees C. This is because the gallium nitrate
      hydrate precursor promoted the decomposition and dehydroxylation reaction for
      Zn(CH3COO)2.2H2O and/or SnCl2.2H2O precursors. The concentrations of carbon and
      chloride in gallium nitrate hydrate added ZTO films annealed at 400  degrees C
      have a lower value (C 0.65, Cl 0.65 at. %) compared with those of ZTO films (C
      3.15, Cl 0.82 at. %). Absorption bands at 416, 1550, and 1350 cm(-1) for GaZTO:N
      films indicated the presence of ZnGa2O4, N-H, and N?O groups by Fourier transform
      infrared spectroscopy measurement, respectively. As a result, an inverted
      staggered Ga-ZTO:N TFT exhibited a mobility of 4.84 cm(2) V(-1) s(-1) in the
      saturation region, a subthreshold swing of 0.35 V/decade, and a threshold gate
      voltage (Vth) of 0.04 V. In addition, the instability of Vth values of the ZTO
      TFTs under positive bias stress conditions was suppressed by adding Ga and N from
      13.6 to 3.17 V, which caused a reduction in the oxygen-related defects located
      near the conduction band. 

PMID- 24892384
TI  - Efficient photoelectrochemical hydrogen generation using heterostructures of Si
      and chemically exfoliated metallic MoS2.
AB  - We report the preparation and characterization of highly efficient and robust
      photocathodes based on heterostructures of chemically exfoliated metallic 1T-MoS2
      and planar p-type Si for solar-driven hydrogen production. Photocurrents up to
      17.6 mA/cm(2) at 0 V vs reversible hydrogen electrode were achieved under
      simulated 1 sun irradiation, and excellent stability was demonstrated over long
      term operation. Electrochemical impedance spectroscopy revealed low charge
      transfer resistances at the semiconductor/catalyst and catalyst/electrolyte
      interfaces, and surface photoresponse measurements also demonstrated slow carrier
      recombination dynamics and consequently efficient charge carrier separation,
      providing further evidence for the superior performance. Our results suggest that
      chemically exfoliated 1T-MoS2/Si heterostructures are promising earth-abundant
      alternatives to photocathodes based on noble metal catalysts for solar-driven
      hydrogen production. 

PMID- 24892385
TI  - The role of electrostatics in protein-protein interactions of a monoclonal
      antibody.
AB  - Understanding how protein-protein interactions depend on the choice of buffer,
      salt, ionic strength, and pH is needed to have better control over protein
      solution behavior. Here, we have characterized the pH and ionic strength
      dependence of protein-protein interactions in terms of an interaction parameter
      kD obtained from dynamic light scattering and the osmotic second virial
      coefficient B22 measured by static light scattering. A simplified protein-protein
      interaction model based on a Baxter adhesive potential and an electric double
      layer force is used to separate out the contributions of longer-ranged
      electrostatic interactions from short-ranged attractive forces. The ionic
      strength dependence of protein-protein interactions for solutions at pH 6.5 and
      below can be accurately captured using a Deryaguin-Landau-Verwey-Overbeek (DLVO)
      potential to describe the double layer forces. In solutions at pH 9, attractive
      electrostatics occur over the ionic strength range of 5-275 mM. At intermediate
      pH values (7.25 to 8.5), there is a crossover effect characterized by a
      nonmonotonic ionic strength dependence of protein-protein interactions, which can
      be rationalized by the competing effects of long-ranged repulsive double layer
      forces at low ionic strength and a shorter ranged electrostatic attraction, which
      dominates above a critical ionic strength. The change of interactions from
      repulsive to attractive indicates a concomitant change in the angular dependence
      of protein-protein interaction from isotropic to anisotropic. In the second part
      of the paper, we show how the Baxter adhesive potential can be used to predict
      values of kD from fitting to B22 measurements, thus providing a molecular basis
      for the linear correlation between the two protein-protein interaction
      parameters. 

PMID- 24892386
TI  - Chiroptical properties of nona- and dodecamethoxy cryptophanes.
AB  - Enantiopure cryptophane derivatives bearing nine (2, 3) and 12 (4) methoxy
      substituents attached on the six aromatic rings were separated by HPLC using
      chiral stationary phases. The chiroptical properties of compounds 2-4 were
      determined from polarimetry, electronic circular dichroism (ECD), and vibrational
      circular dichroism (VCD) experiments and were compared to those of cryptophane-A
      (1) derivative. ECD spectra of 1 and 4 were calculated by time-dependent density
      functional theory (TDDFT) to determine the absolute configuration (AC) of
      cryptophane derivatives. The (+)-PP absolute configuration was thus established
      for the anti-cryptophane-A (1) and its congeners 2 and 4. VCD experiments
      associated with DFT calculations confirmed the (+)-PP configuration of anti
      compounds 2 and 4 and established the (+)-PM configuration of the syn-3 compound
      as well. This study revealed the preferential all-trans (TTT) conformation of the
      three ethylenedioxy linkers for the CHCl3@1, CHCl3@3, and CHCl3@4 complexes,
      whereas the GTT conformation was found the most favorable for the CHCl3@2
      complex. 

PMID- 24892387
TI  - Arsenic speciation in Australian-grown and imported rice on sale in Australia:
      implications for human health risk.
AB  - Rice is an important route of arsenic (As) exposure to humans, especially
      populations with rice-based diets. Human health risk of As varies greatly with
      rice variety and country of origin. The purpose of the present study was to
      determine total and speciated As in Australian-grown and imported rice on sale in
      Australia to assess their health risk to consumers. The total As (tAs)
      concentrations in Australian-grown organic brown, medium grain brown, and organic
      white rice were 438+/-23, 287+/-03, and 283+/-18 MUg kg(-1) dry weight (d wt),
      respectively. In Bangladeshi, Indian, Pakistani, and Thai rice imported and on
      sale in Australia, tAs concentrations were 56+/-05, 92+/-10, 82+/-06 and 172+/-24
      MUg kg(-1), respectively. Asian rice contained mainly inorganic As (iAs; 86-99%),
      whereas 18-26% of the tAs in Australian-grown rice was dimethylarsinic acid
      (DMA). Relatively higher concentrations of tAs in Australian-grown rice than that
      in imported rice of Asian origin suggest that Australian-grown rice may be a
      health risk for the consumers. It was estimated that Australian-grown organic
      brown rice can contribute up to 98% of the FAO/WHO recommended maximum tolerable
      daily intake limit of iAs (2.1 MUg kg(-1) body wt day(-1)) for Asian immigrants.
      However, other Australian consumers including European immigrants are unlikely to
      be at risk to As from rice diets due to their lower rice consumption rates than
      that of Asian immigrants. The risk assessment showed that imported rice on sale
      in Australia was likely to pose a lower health risk to consumers than Australian
      grown rice.

PMID- 24892389
TI  - Experimental and theoretical investigation on the outer valence electronic
      structure of cyclopropylamine by (e, 2e) electron momentum spectroscopy.
AB  - The binding energy spectra and electron momentum distributions for the outer
      valence molecular orbitals of gaseous cyclopropylamine (CPA) have been measured
      by (e, 2e) electron momentum spectrometer employing noncoplanar asymmetric
      geometry at the impact energy of 2500 eV. The experimental results are
      interpreted on the basis of the quantitative calculations of the ionization
      energies and the relevant molecular orbitals at benchmark theoretical levels
      using the outer-valence Green's function method, the symmetry-adapted cluster
      configuration interaction method, and the density functional theory with B3LYP
      hybrid functional. The total energies of the trans and gauche conformers of CPA
      are also calculated by the second-order Moller-Plesset perturbation theory with
      large basis sets and the derived enthalpy differences (2.02-2.12 kcal/mol) are
      consistent with the previous experimental data (2.19 kcal/mol). The theoretical
      binding energy spectra and electron momentum distributions, in which the relative
      abundances of trans and gauche are taken into account, are generally in
      accordance with the experimental results except for the ionization band from the
      trans 8a' and gauche 11a orbitals. The discrepancy is explained qualitatively in
      view of the picture of molecular geometry change at the instant of ionization. 

PMID- 24892388
TI  - Structural and energetic insight into the cross-seeding amyloid assemblies of
      human IAPP and rat IAPP.
AB  - The misfolding and aggregation of human islet amyloid polypeptide (hIAPP or
      amylin) into small oligomers and large amyloid fibrils is believed to be
      responsible for the dysfunction and death of pancreatic beta-cells in diabetes
      type II. However, rat IAPP (rIAPP), which differs from the hIAPP by only 6 of 37
      residues, lacks the ability to form amyloid fibrils and to induce cell death.
      Little is known about the cross-sequence interactions and cross-seeding
      structures between hIAPP and rIAPP peptides. Herein using explicit-solvent
      molecular dynamics (MD) simulations, we modeled and simulated different
      heteroassemblies formed by the amyloidogenic hIAPP and the nonamyloidogenic rIAPP
      peptides. Simulations showed that the U-shaped hIAPP monomer and oligomers can
      interact with conformationally similar rIAPP to form stable complexes and to
      coassemble into heterogeneous structures. Stable heterointeractions between hIAPP
      and rIAPP were shown to arise from hydrophobic contacts and hydrogen bonds at the
      interface, particularly at N- and C-terminal beta-sheet regions. Because of the
      enhanced interpeptide interactions at the interface, upon binding to hIAPP
      oligomers, the beta-sheet population of rIAPP was greatly increased as compared
      to that of rIAPP alone. More importantly, the conformational energies of rIAPP
      monomers at the bound state were observed to be consistently higher than those of
      rIAPP monomers at the unbound state. However, rIAPP monomers enable one to adopt
      different conformations and follow different pathways for associating with hIAPP
      from the high energy of the bound state to the low energy of the unbound state,
      without encountering any large and abrupt energy barrier. In parallel, AFM study
      of cross-aggregation of hIAPP and rIAPP provided additional evidence that hIAPP
      can seed with rIAPP to form hybrid fibrils at all concentrations similar to pure
      hIAPP fibrils. This work demonstrates the existence of cross-interactions between
      the two different IAPP peptides, which provides an improved fundamental
      understanding of the cross-seeding of different amyloid sequences toward amyloid
      aggregation and toxicity mechanisms. 

PMID- 24892390
TI  - Complications in the management of bladder trauma in a third level hospital.
AB  - OBJECTIVES: To determine the frecuency of complications during the management of
      bladder trauma and its associated factors in a third level reference Hospital.
      METHODS: A cross-sectional study of adult patients admitted in a reference
      Hospital from January 2006 to June 2011 with the diagnosis of bladder trauma. We
      identified demographic variables, type of trauma (blunt, penetrating), diagnostic
      method, associated traumatisms, management of bladder traumatism, frequency of
      complications and mortality. Univariate analysis was performed with frequency
      tables, measures of central tendency and dispersion. Similarly, bivariate
      analysis was performed to explore the association between variables. We used chi
      square test for categorical variables and Student's t test to compare
      quantitative variables. RESULTS: We reviewed 40 medical records, which met the
      eligibility criteria. The median age was 27 years (range 16-;67) and 85% (34
      patients) were male. Twenty-nine patients (72.5%) had penetrating injuries, being
      mainly firearm projectile (96.55%) and 11 patients (27.5%) blunt injuries. Most
      patients had intraoperative diagnosis (67.5%), while 25%, 5% and 2% were
      diagnosed by CT-cystography, cystoscopy and voiding cystography respectively. 70%
      (28 patients) had intraperitoneal bladder injuries. Of the forty patients
      enrolled, thirty six (90%) underwent surgery, while only four (10%) received
      conservative management. A total of ten patients (25%) had some type of
      complication. The most frequent was persistent hematuria (40%) followed by
      surgical site infection (30%), orchitis (20%), urinary tract infection (10%),
      urine leakage through the operative site, or to the peritoneal cavity (10%). No
      mortality was detected. On the bivariate logistic regression model type of
      trauma, number of injuries, performance of cystostomy, use of perivesical
      drainage tube, chest trauma and small bowel trauma, no association was found with
      the presence of complications. CONCLUSIONS: The frequency of complications was
      25%. The presence of gross hematuria after 72 hours of trauma was found to be the
      most common complication. The type of trauma, performance or not performance of
      cystostomy, perivesical drain, presence of associated lesions in chest or small
      bowel were not associated with complications.

PMID- 24892391
TI  - Review of a series of cystectomies in women for bladder cancer:Complications and
      quality of life.
AB  - OBJECTIVES: To analyze the complications and quality of life after cystectomies
      performed in women with bladder cancer at our hospital. METHODS: Descriptive
      analysis of demographic data and early/late complications of cystectomies and
      urinary diversions performed in women at our hospital between 1990-2010. We also
      assessed quality of life using the Functional Assessment of Cancer Therapy
      Bladder Cancer (ACT-BL) questionnaire and a comparison was drawn between groups
      of clinical variables. RESULTS: Out of 265 cystectomies, 25 (10%) were performed
      in women. The predominant urinary diversion was ureterosigmoidostomy (60%),
      followed by cutaneous ureterostomy (16%), orthotopic ileal neo-bladder Studer
      pouch (12%), ileal conduit (10%) and permanent nephrostomy (4%). Mean age was
      55.75 years. The most commonly occurring early complications were prolonged ileus
      (20%) and urinary fistula (20%). Late complications included hydronephrosis (32%)
      and pyelonephritis (32%). The results of quality of life questionnaires were very
      similar for the different types of urinary diversions, with a mean score of 104.5
      out of 156 points. CONCLUSIONS: Radical cystectomy is a high-risk procedure
      associated with many complications. In women, ureterosigmoidostomy may be a good
      choice for urinary diversion in selected patients, with a quality of life very
      similar to those with different urinary diversions.

PMID- 24892393
TI  - Urinary incontinence during pregnancy and postpartum. Associated risk factors and
      influence of pelvic floor exercises.
AB  - OBJECTIVES: To determine the prevalence of urinary incontinence (UI) before
      pregnancy, in the third trimester and postpartum. To analyze its influence on
      quality of life and associated potential risk factors and the efficacy of pelvic
      floor exercises. METHODS: Prospective study in 413 pregnant women. The modified
      ICIQ-SF incontinence questionnaire was given to the pregnant women at the end of
      the third quarter. This questionnaire was administered by telephone at 3 and 6
      months postpartum. The influence of several risk factors for UI in pregnancy and
      postpartum were analyzed. Patients with persistent UI at 6 months postpartum were
      trained to do pelvic floor exercises. RESULTS: Patients with UI before pregnancy
      were excluded from the study. UI in the third trimester was 31%. Analyzed risk
      factors did not condition a higher percentage of UI. Prevalence of UI was 11.3%
      at 3 months postpartum and 6.9% at 6 months. 70% of the incontinent patients
      already had it during pregnancy and it appeared de novo post-delivery in 30% of
      the patients. Prevalence of UI after delivery was higher in women with UI in
      pregnancy and lower in caesarean cases. Most women improved with pelvic floor
      exercises. CONCLUSIONS: Analysed risk factors did not significantly increase UI
      in pregnancy. Prevalence of UI after delivery is higher in women with UI in
      pregnancy and lower in caesarean cases. Postpartum pelvic floor exercises for
      three months in patients with persistent stress UI at 6 months postpartum clearly
      improved the degree of continence.

PMID- 24892392
TI  - Salvage radical prostatectomy after radiotherapy.
AB  - OBJECTIVES: To determine the oncological and functional results obtained after
      salvage radical prostatectomy (SRP) in patients with recurrence following
      radiotherapy (3 consecutive PSA rises after a nadir until the year 2006, then 2
      ng/mL above nadir ) for prostate cancer (PC), and to analyze the impact of
      different pre-and postoperative variables on biochemical recurrence-free survival
      (BCR-free survival). METHODS: Retrospective analysis of 29 cases treated with
      SRP, 23 cases of conventional technique and 6 cases assisted by the Da Vinci
      surgical system between August 2004 and March 2012 at the Hospital Italiano de
      Buenos Aires. There was an attempt to preserve neurovascular bundles in cT1c
      patients with low tumor volume, Gleason score 7 or less, and favorable surgical
      anatomy. The degrees of postoperative incontinence and erectile function were
      recorded. The overall survival, the disease-specific survival, and the BCR-free
      survival were assessed. The BCR-free survival was compared among groups in
      accordance with the pre-and post-operative variables. RESULTS. No
      complications,injury to nearby organs or blood transfusions were recorded. Of all
      the patients, 85.7% showed normal continence (no pads used). Eight patients
      (27.5%) preserved their potency with sildenafil. There were 6 positive margins
      for tumor extension, 44.8% of pT3a, and 10.3% pT3b. All patients are alive at
      present, and 58.6% with at least 1 year of follow-up have a PSA with recovery
      criteria (less than 0.02 ng/mL). The biochemical recurrence (BCR) was 41.3%, and
      the estimated 4-year BCR-free survival was 51.7%. Of the groups analyzed, the
      presence of a preoperative Gleason score >=8 and the presence of positive
      surgical margins (PSMs) significantly influenced the BCR-free survival, both in
      the univariate as well as the multivariate analysis (p=0.02 and 0.017,
      respectively). CONCLUSIONS. SRP is a challenging and achievable surgery with an
      acceptable complication rate, and constitutes a chance to cure patients with
      biochemical recurrence following prostate radiotherapy. The presence of a
      preoperative Gleason score >=8, and the presence of PSMs in the specimen increase
      the chances of a BCR after four years post-SRP.

PMID- 24892394
TI  - Retrograde intrarenal surgery (RIRS) in the treatment of calyceal diverticulum
      with lithiasis.
AB  - OBJECTIVES: To evaluate the result of retrograde intrarenal surgery (RIRS)
      assisted by flexible ureterorenoscopy (FURS) and Holmium laser in the treatment
      of lithiasis within calyceal diverticula as a minimally invasive therapeutic
      option. METHODS: We retrospectively evaluated 11 cases of symptomatic lithiasis
      within calyceal diverticula treated between January 2010 and December 2011. We
      defined treatment success as absence of residual stones and absence/disappearance
      of symptomatology over the course of follow-up. We describe the RIRS technique
      and maneuvers for locating the diverticulum, opening the neck, and fragmenting
      intradiverticular lithiasis. RESULTS: The most frequently experienced symptom was
      flank pain (72.7%). The size of the lithiasis treated ranged from 7-20 mm. The
      overall success rate of RIRS was approximately 73% (absence of lithiasis and
      disappearance of symptoms) with an average follow-up of 13.3 months. Three cases
      were not solved by RIRS (2 due to unsuccessful location of the neck, 1 due to
      persistence of lithiasis and symptoms) . Cases of unsuccessful location were
      treated with laparoscopic surgery. CONCLUSION: RIRS assisted by FURS and Holmium
      laser is an effective and minimally invasive procedure for the treatment of
      lithiasis in the interior of the calyceal diverticulum. This treatment's efficacy
      improves upon the results from ESWL (extracorporeal shock wave lithotripsy( and
      equals that of the percutaneous method, exhibiting a lower rate of complications.

PMID- 24892395
TI  - Multilocular cystic nephroma: A clinical case.
AB  - OBJECTIVE: To describe the clinical presentation, preoperative diagnostic
      possibilities, and treatment of cystic nephroma. METHODS: We describe a case of
      cystic nephroma in an adult male and show that, both in our patient and in the
      literature, a definitive diagnosis can only be obtained postoperatively, even
      when there is a reasonable clinical suspicion. CONCLUSIONS: Cystic nephroma is
      rare, and some authors consider it a questionable entity. However, it should be
      distinguished from renal cystic neoplasms, which can resemble the condition.

PMID- 24892396
TI  - AA type primary amyloidosis of the urinary bladder: Clinical case and
      bibliographic review.
AB  - OBJECTIVE: Amyloidosis is a disease characterised by deposition of eosinophilic
      hyaline material in different tissues. Urinary bladder involvement is uncommon
      with less than 200 cases of the primary form published in the literature. We
      present a new case of primary AA type amyloidosis of the urinary bladder (typical
      of secondary forms). METHODS: A 66-year-old male was seen in the outpatient
      urology consultation with several-weeks history intermittent haematuria with
      decreased voiding urinary calibre. In addition, he had intense nocturia, 10-12
      times per night, and occasional urgency. Physical examination of the abdomen and
      genitals was unremarkable. Urine sediment and blood tests were normal. Urine
      cytology studies were requested and revealed urothelial cells with no atypical
      cells and a moderate quantity of neutrophils and erythrocytes. Cystoscopy was
      performed and revealed yellowish erythematous lesions at the level of the
      vesicoureteric junction and the fundus. The lesions were biopsied. Pathology
      studies revealed urothelial mucosa with marked chronic inflammation and
      accumulations of amyloid-appearing hyaline material in the area of the vessels
      with green birefringence on polarised light. TUR of the bladder was later
      performed with the goal of completely resecting the lesion. The result of the
      pathology studies confirmed the biopsy findings and immunohistochemistry studies
      revealed AA type amyloid (typical of secondary forms). RESULTS: Two years after
      the intervention, the patient remains asymptomatic with normal endoscopic follow
      up studies. CONCLUSIONS: Primary AA type amyloidosis of the bladder is a very
      uncommon pathology with few cases reported in the international urology
      literature. Nevertheless, we must keep it in mind in the differential diagnosis
      when faced with a patient with haematuria and/or persistent urinary symptoms.

PMID- 24892397
TI  - Collateral urethral duplication in an adult.
AB  - OBJECTIVE: Congenital anomalies or malformations of the urethra that involve
      number are extremely rare and only 7 cases of trifurcation of the urethra and
      under 500 cases of urethral duplication have been described. METHODS: In the case
      we present, urethral duplication was diagnosed in adulthood, even though glans
      malformation with 2 urethral orifices was clearly evident and only 1 was
      functional. RESULTS: The condition is usually diagnosed in childhood due to the
      presence of 2 urethral meatus or from double stream if both are functional; at
      other times, the condition is diagnosed from complications that trigger
      infections or obstruction or if it is associated with more extensive
      malformations. CONCLUSIONS: Urethral duplication is an extremely rare birth
      defect, and diagnosis in adulthood is even more uncommon. No single embryologic
      argument explains all the anatomic variants of urethral duplication. The
      treatment of the urethral duplication should be individualized according to the
      type of duplication and the clinical symtoms.

PMID- 24892398
TI  - Intraabdominal germinal tumor originated from an ectopic testis.
AB  - OBJECTIVE: We report the case of a 54 year old man with an intraabdominal
      germinal tumor originated from an ectopic testis, and its treatment. METHODS: The
      tumor was diagnosed with percutaneous biopsy and treated with three cycles of BEP
      (bleomycin etoposide, platinum ), showing an important decrease of its size.
      Treatment was completed with the excision of the remnant mass and regional
      lymphadenectomy. CONCLUSIONS: Abdominal masses in patients with a testicle
      outside the scrotum can be germ cell tumors and should be considered during the
      diagnosis.

PMID- 24892399
TI  - Metastasis of rectal adenocarcinoma to the penis.
AB  - OBJECTIVE: To report a clinical case of penile metastasis of a rectal
      adenocarcinoma. METHODS: We report the case of a 78-year-old male with a clinical
      history of rectum adenocarcinoma. The management included an anterior rectum
      resection and postoperative combination of neoadjuvant chemo and radiotherapy.
      Eight months after the operation, a painful solitary nodular lesion on the glans
      penis was diagnosed. We performed a needle biopsy (Tru-cut). RESULTS:
      Histological examination confirmed metastasis of the rectal tumour. We performed
      partial penectomy. CONCLUSIONS: The incidence of penile metastasis is extremely
      low. In a large number of cases the primary tumour is localized in the genito
      urinary tract, less likley they originate from other organs. The treatment,
      depending to each case, is mostly palliative due to the poor prognosis of
      disease.

PMID- 24892400
TI  - Hemangioma of the glans penis.

PMID- 24892401
TI  - Testicular rupture after scrotal trauma.

PMID- 24892402
TI  - An entrustable professional activity (EPA) for handoffs as a model for EPA
      assessment development.
AB  - Medical education is moving toward assessment of educational outcomes rather than
      educational processes. The American Board of Internal Medicine and American Board
      of Pediatrics milestones and the concept of entrustable professional activities
      (EPA)--skills essential to the practice of medicine that educators progressively
      entrust learners to perform--provide new approaches to assessing outcomes.
      Although some defined EPAs exist for internal medicine and pediatrics, the
      continued development and implementation of EPAs remains challenging. As
      residency programs are expected to begin reporting milestone-based performance,
      however, they will need examples of how to overcome these challenges. The authors
      describe a model for the development and implementation of an EPA using the
      resident handoff as an example. The model includes nine steps: selecting the EPA,
      determining where skills are practiced and assessed, addressing barriers to
      assessment, determining components of the EPA, determining needed assessment
      tools, developing new assessments if needed, determining criteria for advancement
      through entrustment levels, mapping milestones to the EPA, and faculty
      development. Following implementation, 78% of interns at the University of
      Minnesota Medical School were observed giving handoffs and provided feedback. The
      authors suggest that this model of EPA development--which includes engaging
      stakeholders, an iterative process to describing the behavioral characteristics
      of each domain at each level of entrustment, and the development of specific
      assessment tools that support both formative feedback and summative decisions
      about entrustment--can serve as a model for EPA development for other clinical
      skills and specialty areas.

PMID- 24892403
TI  - Measuring reflection on participation in quality improvement activities for
      maintenance of certification.
AB  - PURPOSE: To validate a measure of reflection on participation in quality
      improvement (QI) activities and to identify associations with characteristics of
      QI projects, participants, and teams. METHOD: This was a prospective validation
      study of all Mayo Clinic team participants who submitted QI projects for
      maintenance of certification (MOC) credit from 2010 to 2012. The authors
      developed a measure of reflection on participation in QI activities and explored
      associations between participants' overall reflection scores and characteristics
      of projects, participants, and teams. RESULTS: A total of 922 participants (567
      physicians) on 118 teams completed QI projects and reflections. Factor analysis
      revealed a two-dimensional model with good internal consistency reliabilities
      (Cronbach alpha) for high (0.85) and low (0.81) reflection. Reflection scores
      (mean [standard deviation]) were associated with projects that changed practice
      (yes: 4.30 [0.51]; no: 3.71 [0.57]; P < .0001), changed the health care system
      (yes: 4.25 [0.54]; no: 4.03 [0.62]; P < .0001), and impacted patient safety (P <
      .0001). Physicians' reflection scores (4.27 [0.57]) were higher than support
      staff scores (4.07 [0.55]; P = .0005). A positive association existed between
      reflection scores and the number of QI roles per participant (P < .0001). There
      were no associations with participant gender, team size, or team diversity.
      CONCLUSIONS: The authors identified associations between participant reflection
      and the impact of QI projects, participants' professional roles, and
      participants' involvement with projects. With further study, the authors
      anticipate that the new measure of reflection will be useful for determining
      meaningful engagement in MOC.

PMID- 24892404
TI  - iMedEd: the role of mobile health technologies in medical education.
AB  - Mobile health (mHealth) technologies have experienced a recent surge in attention
      because of their potential to transform the delivery of health care. This
      enthusiasm is partly due to the near ubiquity of smartphones and tablets among
      clinicians, as well as to the stream of mobile medical apps and devices being
      created. While much discussion has been devoted to how these tools will impact
      the practice of medicine, surprisingly little has been written on the role these
      technologies will play in medical education. In this commentary the authors
      describe the opportunities, applications, and challenges of mHealth apps and
      devices in medical education and argue that medical schools should make efforts
      to integrate these technologies into their curricula. By not doing so, medical
      educators risk producing a generation of clinicians underprepared for the
      changing realities of medical practice brought on by mHealth technologies. 

PMID- 24892405
TI  - From theory to practice: making entrustable professional activities come to life
      in the context of milestones.
AB  - Entrustable professional activities (EPAs) are gaining traction across the globe
      as a practical way to teach and assess competencies in the clinical setting. Full
      scale implementation, though, has only taken place in obstetrics-gynecology in
      the Netherlands and in psychiatry in Australia and New Zealand. As with any
      conceptual framework, implementation in different contexts will require
      adaptations. For example, implementation in the United States will need to
      incorporate the Accreditation Council for Graduate Medical Education's
      competencies and the recently completed milestones for each of the specialties.
      In this issue, an article by Aylward and colleagues describes the process for
      implementing a handoff communication EPA, using milestones as the basis for the
      assessment tool. The explicit linkage of the milestones with the EPA assessment
      allows a more definitive "picture" of the learner to emerge at each advancing
      level of performance of the EPA. This "picture" can be shared with those directly
      observing the learner and thus provides a potential model for a more reliable
      assessment of learners performing EPAs and perhaps a more consistent approach to
      entrustment decisions. The authors hope that Aylward and colleagues' article will
      be one of many that aim to help the medical education community understand how to
      implement EPAs as a framework for competency demonstration, as educators try to
      determine what works, under what conditions and in what settings. Only through a
      committed effort to share lessons learned can the promise of the theory be
      translated to practice in the field.

PMID- 24892406
TI  - Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics
      approach.
AB  - Human cancers exhibit strong phenotypic differences that can be visualized
      noninvasively by medical imaging. Radiomics refers to the comprehensive
      quantification of tumour phenotypes by applying a large number of quantitative
      image features. Here we present a radiomic analysis of 440 features quantifying
      tumour image intensity, shape and texture, which are extracted from computed
      tomography data of 1,019 patients with lung or head-and-neck cancer. We find that
      a large number of radiomic features have prognostic power in independent data
      sets of lung and head-and-neck cancer patients, many of which were not identified
      as significant before. Radiogenomics analysis reveals that a prognostic radiomic
      signature, capturing intratumour heterogeneity, is associated with underlying
      gene-expression patterns. These data suggest that radiomics identifies a general
      prognostic phenotype existing in both lung and head-and-neck cancer. This may
      have a clinical impact as imaging is routinely used in clinical practice,
      providing an unprecedented opportunity to improve decision-support in cancer
      treatment at low cost. 

PMID- 24892408
TI  - Identification of genomic loci associated with Rhodococcus equi susceptibility in
      foals.
AB  - Pneumonia caused by Rhodococcus equi is a common cause of disease and death in
      foals. Although agent and environmental factors contribute to the incidence of
      this disease, the genetic factors influencing the clinical outcomes of R. equi
      pneumonia are ill-defined. Here, we performed independent single nucleotide
      polymorphism (SNP)- and copy number variant (CNV)-based genome-wide association
      studies to identify genomic loci associated with R. equi pneumonia in foals.
      Foals at a large Quarter Horse breeding farm were categorized into 3 groups: 1)
      foals with R. equi pneumonia (clinical group [N = 43]); 2) foals with
      ultrasonographic evidence of pulmonary lesions that never developed clinical
      signs of pneumonia (subclinical group [N = 156]); and, 3) foals without clinical
      signs or ultrasonographic evidence of pneumonia (unaffected group [N = 49]). From
      each group, 24 foals were randomly selected and used for independent SNP- and CNV
      based genome-wide association studies (GWAS). The SNP-based GWAS identified a
      region on chromosome 26 that had moderate evidence of association with R. equi
      pneumonia when comparing clinical and subclinical foals. A joint analysis
      including all study foals revealed a 3- to 4-fold increase in odds of disease for
      a homozygous SNP within the associated region when comparing the clinical group
      with either of the other 2 groups of foals or their combination. The region
      contains the transient receptor potential cation channel, subfamily M, member 2
      (TRPM2) gene, which is involved in neutrophil function. No associations were
      identified in the CNV-based GWAS. Collectively, these data identify a region on
      chromosome 26 associated with R. equi pneumonia in foals, providing evidence that
      genetic factors may indeed contribute to this important disease of foals.

PMID- 24892412
TI  - Take care in the kitchen: avoiding cooking-related pollutants.

PMID- 24892409
TI  - Direct effect of 10-valent conjugate pneumococcal vaccination on pneumococcal
      carriage in children Brazil.
AB  - BACKGROUND: 10-valent conjugate pneumococcal vaccine/PCV10 was introduced in the
      Brazilian National Immunization Program along the year of 2010. We assessed the
      direct effectiveness of PCV10 vaccination in preventing nasopharyngeal/NP
      pneumococcal carriage in infants. METHODS: A cross-sectional population-based
      household survey was conducted in Goiania Brazil, from December/2010
      February/2011 targeting children aged 7-11 m and 15-18 m. Participants were
      selected using a systematic sampling. NP swabs, demographic data, and vaccination
      status were collected from 1,287 children during home visits. Main outcome and
      exposure of interest were PCV10 vaccine-type carriage and dosing schedules (3p+0,
      2p+0, and one catch-up dose), respectively. Pneumococcal carriage was defined by
      a positive culture and serotyping was performed by Quellung reaction. Rate
      ratio/RR was calculated as the ratio between the prevalence of vaccine-types
      carriage in children exposed to different schedules and unvaccinated for PCV10.
      Adjusted RR was estimated using Poisson regression. PCV10 effectiveness/VE on
      vaccine-type carriage was calculated as 1-RR*100. RESULTS: The prevalence of
      pneumococcal carriage was 41.0% (95%CI: 38.4-43.7). Serotypes covered by PCV10
      and PCV13 were 35.2% and 53.0%, respectively. Vaccine serotypes 6B (11.6%), 23F
      (7.8%), 14 (6.8%), and 19F (6.6%) were the most frequently observed. After
      adjusted for confounders, children who had received 2p+0 or 3p+0 dosing schedule
      presented a significant reduction in pneumococcal vaccine-type carriage, with
      PCV10 VE equal to 35.9% (95%CI: 4.2-57.1; p = 0.030) and 44.0% (95%CI: 14.-63.5;
      p = 0.008), respectively, when compared with unvaccinated children. For children
      who received one catch-up dose, no significant VE was detected (p = 0.905).
      CONCLUSION: PCV10 was associated with high protection against vaccine-type
      carriage with 2p+0 and 3p+0 doses for children vaccinated before the second
      semester of life. The continuous evaluation of carriage serotypes distribution is
      likely to be useful for evaluating the long-term effectiveness and impact of
      pneumococcal vaccination on serotypes reduction.

PMID- 24892410
TI  - A novel SNP associated with nighttime pulse pressure in young-onset hypertension
      patients could be a genetic prognostic factor for cardiovascular events in a
      general cohort in Taiwan.
AB  - BACKGROUND: Pulse pressure (PP) is a risk factor for cardiovascular disease. It
      has been reported that ambulatory blood pressure (BP) and nighttime BP parameters
      are heritable traits. However, the genetic association of pulse pressure and its
      clinical impact remain undetermined. METHOD AND RESULTS: We conducted a genome
      wide association study of PP using ambulatory BP monitoring in young-onset
      hypertensive patients and found a significant association between nighttime PP
      and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted
      gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at
      rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 +/
      7.3 mm Hg; CT, 39.1 +/- 6.0 mm Hg; CC, 38.9 +/- 6.3 mm Hg; p<0.05,). The T risk
      allele resulted in a cumulative increase in nighttime PP (beta = 1.036 mm Hg, se.
      = 0.298, p<0.001 per T allele). An independent community-based cohort containing
      3325 Taiwanese individuals (mean age, 50.2 years) was studied to investigate the
      genetic impact of rs897876 polymorphisms in determining future cardiovascular
      events. After an average 7.79 +/- 0.28 years of follow-up, the TT genotype of
      rs897876 was independently associated with an increased risk (in a recessive
      model) of coronary artery disease (HR, 2.20; 95% CI, 1.20-4.03; p = 0.01) and
      total cardiovascular events (HR, 1.99; 95% CI, 1.29-3.06; p = 0.002), suggesting
      that the TT genotype of rs897876C, which is associated with nighttime pulse
      pressure in young-onset hypertension patients, could be a genetic prognostic
      factor of cardiovascular events in the general cohort. CONCLUSION: The TT
      genotype of rs897876C at 2p14 identified in young-onset hypertensive had higher
      nighttime PP and could be a genetic prognostic factor of cardiovascular events in
      the general cohort in Taiwan.

PMID- 24892413
TI  - Topiramate for alcoholism treatment: novel pharmacogenetic evidence for the
      journey to personalized medicine?

PMID- 24892414
TI  - Bromeliad selection by two salamander species in a harsh environment.
AB  - Bromeliad phytotelmata are frequently used by several Neotropical amphibian taxa,
      possibly due to their high humidity, microclimatic stability, and role as a
      refuge from predators. Indeed, the ability of phytotelmata to buffer against
      adverse environmental conditions may be instrumental in allowing some amphibian
      species to survive during periods of environmental change or to colonize sub
      optimal habitats. Association between bromeliad traits and salamanders has not
      been studied at a fine scale, despite the intimate association of many salamander
      species with bromeliads. Here, we identify microhabitat characteristics of
      epiphytic bromeliads used by two species of the Bolitoglossa morio group (B.
      morio and B. pacaya) in forest disturbed by volcanic activity in Guatemala.
      Specifically, we measured multiple variables for bromeliads (height and position
      in tree, phytotelma water temperature and pH, canopy cover, phytotelma size, leaf
      size, and tree diameter at breast height), as well as salamander size. We
      employed a DNA barcoding approach to identify salamanders. We found that B. morio
      and B. pacaya occurred in microsympatry in bromeliads and that phytotelmata size
      and temperature of bromeliad microhabitat were the most important factors
      associated with the presence of salamanders. Moreover, phytotelmata with higher
      pH contained larger salamanders, suggesting that larger salamanders or aggregated
      individuals might modify pH. These results show that bromeliad selection is
      nonrandom with respect to microhabitat characteristics, and provide insight into
      the relationship between salamanders and this unique arboreal environment. 

PMID- 24892415
TI  - Secondary skull reconstruction with autogenous split calvarial bone grafts versus
      nonautogenous materials.
AB  - BACKGROUND: Skull reconstructions, which can be required for various reasons,
      including decompressive craniectomy, trauma, and tumors, are challenging issues
      in plastic surgery. Moreover, obtaining a low complication ratio in secondary
      skull reconstructions is more difficult than in primary skull reconstructions.
      Because standardized protocols have not been established, we here compare
      cranioplasty performance using fresh autogenous split calvarial bone grafts and
      allogenic or alloplastic materials in secondary revisional cases. METHODS:
      Surgical correction of skull defects was performed in 25 patients in our center
      between 2005 and 2012. Only secondary cranioplasty cases were reviewed
      retrospectively. There were 17 men and 8 women, with ages ranging from 8 to 62
      years at the time of surgery. The mean follow-up was 55.6 months. The surgical
      procedure in each case was a routine cranioplasty. In most of the cases, a 1
      piece split calvarial bone graft was used while minimizing the separation of the
      bone flap into multiple pieces. RESULTS: In comparison with the skull
      reconstructional approach using nonautogenous materials, the functional and
      esthetic results of skull reconstruction using autogenous calvarial bone grafts
      were better and more consistent in secondary revisional cases. The group that
      received autogenous calvarial bone grafts showed a reconstruction success rate of
      80% without esthetic and functional complications. In contrast, the group that
      received nonautogenous materials had a 30% success rate. CONCLUSIONS: Secondary
      cranial defect reconstructions with autogenous calvarial bone grafts showed
      better functional and esthetic results than skull reconstructions with
      nonautogenous materials.

PMID- 24892416
TI  - Upregulation of Nav1.8 in demyelinated facial nerves might be relevant to the
      generation of hemifacial spasm.
AB  - Our previous studies demonstrated that the abnormal muscle response could vanish
      when the ipsilateral superior cervical ganglion was removed and reappear when
      norepinephrine was dripped at the neurovascular conflict site. Evidentially, we
      believed that the mechanism of hemifacial spasm should involve emersion of
      ectopical action potential in the compressed facial nerve fibers. As the action
      potential is ignited by ion channel opening, we focused on Nav1.8 that has been
      found overexpressed in peripheral nerve while damaged. In this study, Moller
      model was adopted, 20 Sprague-Dawley rats underwent drip of norepinephrine, and
      the abnormal muscle response wave was monitored in 14 rats. Antibodies against
      unique epitopes of the alpha subunit of sodium channel isoforms were used to
      detect the Nav1.8 neuronal isoforms, and the immunohistochemistry showed strong
      staining in 13 rats, which were all in the abnormal muscle response positive
      group (P < 0.05). Accordingly, we concluded that the substance of hemifacial
      spasm is an ectopic action potential that emerged on the damaged facial nerve,
      which might be coupled by Nav1.8. 

PMID- 24892417
TI  - Usefulness of serum C-reactive protein level for predicting flap complication
      after performing free microvascular head and neck reconstruction.
AB  - BACKGROUND: Free microvascular head and neck reconstruction requires minimal
      complication and safety. However, clinical observation of the wound in head and
      neck area is very difficult because of its narrow and inaccessible anatomy. Serum
      C-reactive protein (CRP) level is commonly used as a marker of acute inflammatory
      response and quantitative test that shows predictable kinetics. Therefore,
      awareness of natural CRP trend of free microvascular head and neck reconstruction
      may help in the early diagnosis of postoperative complications. The goal of this
      study is to describe the time course of serum CRP level and prove the usefulness
      of CRP as a predictor of postoperative flap wound complication after performing
      free microvascular reconstruction in head and neck area. METHODS: Between June
      2009 and November 2012, we retrospectively analyzed the data of 25 patients who
      received free microvascular tissue transfer for head and neck reconstruction at
      Ajou University Hospital. The characteristics of patients and surgical
      information were analyzed. From the first day after surgery, CRP levels were
      daily measured for 2 weeks. The average CRP values were daily calculated for the
      normal group and the complicated group and compared between each groups. The
      amount of time taken to reach the peak CRP level and to reach half of the peak
      was compared. RESULTS: A total of 25 patients were included in this study. The
      amount of time taken to reach the peak of the CRP level is significantly less in
      the normal group (2.9 d) than the complicated group (7 d) (P < 0.001).
      Furthermore, the amount of time to reach half of the peak was significantly
      different between groups (7.2 d vs. 10.1 d, respectively, P < 0.05). In the
      normal group (17/25), there were 14 cases which reached peak CRP level before
      postoperative day 4. However, in the complicated group (8/25), there was only 1
      case which reached peak CRP level before postoperative day 4 (P < 0.05). The
      complication rate is 32.7 times higher when CRP value reaches peak on or after
      postoperative day 4 (95% confidence interval, 30.26-35.14; P = 0.002). Patients
      in the complicated group showed significantly elevated CRP levels compared to
      those in the normal group at day 6 to 9 and day 12 to 13 (P < 0.05). CONCLUSION:
      In head and neck reconstructions, the high probability of flap wound
      complications are indicated through the result of having highest CRP values on or
      after postoperative day 4, slow normalization of plasma CRP level, and secondary
      rise in serial CRP values.

PMID- 24892418
TI  - Evaluation of foot perfusion after fibula flap surgery.
AB  - Fibula flap is widely used in reconstruction work, whereas the low extremity
      blood supply alteration was unclear. This study would observe the blood oxygen
      saturation change of foot after harvesting fibula flap. The regional tissue
      oxygen saturation (rSO2) of the lateral side and inner side of feet was measured
      using near-infrared spectroscopy oxygen monitoring system (NIRS) before operation
      and in postoperative day 1 to 7, and the foot of the control side was measured as
      control. The rSO2 of the donor side foot decreased less than 5% (P < 0.05) in the
      first 8 hours after operation and recovered to the level of the control side
      later. NIRS is ideal for measuring rSO2 of donor side foot after fibula flap. The
      rSO2 of the donor side foot decreased less than 5% after fibula flap harvesting. 

PMID- 24892419
TI  - What parental characteristics can predict child maltreatment at the Emergency
      Department? Considering expansion of the Hague Protocol.
AB  - The Hague Protocol considers three parental characteristics of Emergency
      Department adult patients to identify child abuse: (a) domestic violence, (b)
      intoxication, and (c) suicide attempt or auto mutilation. This study investigated
      whether additional parental characteristics could be included to improve the
      chance of detection. Using a nested case-control design, we compared parents
      identified as child abusers who were missed by the Protocol with a matched group
      of nonabusing parents. The parental characteristics used were, among others, all
      physical injuries possibly resulting from domestic violence, psychological, or
      mental complaints that might indicate elevated domestic stress levels and the
      number of Emergency Department visits during the previous year. None of the
      characteristics were statistically significantly associated with child abuse. The
      Hague Protocol will not be improved by adding one or more of the characteristics
      that were investigated. 

PMID- 24892420
TI  - Effects of anterior thalamic nucleus deep brain stimulation in chronic epileptic
      rats.
AB  - Deep brain stimulation (DBS) has been investigated for the treatment of epilepsy.
      In rodents, an increase in the latency for the development of seizures and status
      epilepticus (SE) has been reported in different animal models but the
      consequences of delivering stimulation to chronic epileptic animals have not been
      extensively addressed. We study the effects of anterior thalamic nucleus (AN)
      stimulation at different current intensities in rats rendered epileptic following
      pilocarpine (Pilo) administration. Four months after Pilo-induced SE, chronic
      epileptic rats were bilaterally implanted with AN electrodes or had sham-surgery.
      Stimulation was delivered for 6 h/day, 5 days/week at 130 Hz, 90 usec. and either
      100 uA or 500 uA. The frequency of spontaneous recurrent seizures in animals
      receiving stimulation was compared to that recorded in the preoperative period
      and in rats given sham treatment. To investigate the effects of DBS on
      hippocampal excitability, brain slices from animals receiving AN DBS or sham
      surgery were studied with electrophysiology. We found that rats treated with AN
      DBS at 100 uA had a 52% non-significant reduction in the frequency of seizures as
      compared to sham-treated controls and 61% less seizures than at baseline. Animals
      given DBS at 500 uA had 5.1 times more seizures than controls and a 2.8 fold
      increase in seizure rate as compared to preoperative values. In non-stimulated
      controls, the average frequency of seizures before and after surgery remained
      unaltered. In vitro recordings have shown that slices from animals previously
      given DBS at 100 uA had a longer latency for the development of epileptiform
      activity, shorter and smaller DC shifts, and a smaller spike amplitude compared
      to non-stimulated controls. In contrast, a higher spike amplitude was recorded in
      slices from animals given AN DBS at 500 uA. 

PMID- 24892421
TI  - The in vitro and in vivo antitumor effects of clotrimazole on oral squamous cell
      carcinoma.
AB  - BACKGROUND: Clotrimazole is an antifungal imidazole derivative showing anti-
      neoplastic effect in some tumors, but its anticancer potential is still unclear
      in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the
      antitumor effect of clotrimazole, and to investigate the possible mechanism of
      clotrimazole-mediated antitumor activity in OSCC. METHODOLOGY: In vitro
      experiments, the cell viability and clonogenic ability of three human OSCC cell
      lines CAL27, SCC25 and UM1 were detected after clotrimazole treatment by CCK8
      assay and colony formation assay. Cell cycle progression and apoptosis were
      assessed by flow cytometry, and the involvement of several mediators of apoptosis
      was examined by western blot analysis. Then, the in vivo antitumor effect of
      clotrimazole was investigated in CAL27 xenograft model. Immunohistochemistry and
      western blot analysis were performed to determine the presence of apoptotic cells
      and the expression of Bcl-2 and Bax in tumors from mice treated with or without
      clotrimazole. RESULTS: Clotrimazole inhibited proliferation in all three OSCC
      cell lines in a dose-and time-dependent manner, and significantly reduced the
      colony formation of OSCC cells in vitro. Clotrimazole caused cell cycle arrest at
      the G0/G1 phase. In addition, clotrimazole induced apoptosis in OSCC cells, and
      significantly down-regulated the anti-apoptotic protein Bcl-2 and up-regulated
      the pro-apoptotic protein Bax. Notably, clotrimazole treatment inhibited OSCC
      tumor growth and cell proliferation in CAL27 xenograft model. Clotrimazole also
      markedly reduced Bcl-2 expression and increased the protein level of Bax in tumor
      tissues of xenograft model. CONCLUSION: Our findings demonstrated a potent
      anticancer effect of clotrimazole by inducing cell cycle arrest and cellular
      apoptosis in OSCC.

PMID- 24892422
TI  - Safety and efficacy of Gammaplex(r) in idiopathic thrombocytopenic purpura
      (ClinicalTrials.gov--NCT00504075).
AB  - BACKGROUND AND OBJECTIVES: This multicentre, open-label study investigated the
      safety and efficacy of Gammaplex, a 5% Intravenous Immunoglobulin (IVIg), in
      patients with idiopathic (immune) thrombocytopenic purpura (ITP). MATERIALS AND
      METHODS: Patients were between the ages of 6 and 70 years; had ITP for at least
      six months and had a platelet count <= 20 * 10(9)/L. Eligible patients were dosed
      with 1 g/kg of Gammaplex on two consecutive days, followed by assessment of
      safety and efficacy on Days 3, 5, 9, 14, 21, 32 and 90. Response was defined as
      the increase in platelet count to a threshold of >= 50 * 10(9)/L on or before Day
      9 after the first dose of Gammaplex. RESULTS: All 35 patients received at least
      one infusion of Gammaplex. Twenty-nine (83%) patients responded to Gammaplex,
      similar to the historical control, with a 95% lower one-sided confidence interval
      of 68.9%. Median duration of response was 10.0 days, with an overall reduction in
      bleeding episodes. Gammaplex provided supranormal concentrations of total IgG;
      mean peak concentration (Cmax) of 45.3 g/L (4.53 g/dL), with a mean half-life of
      28.5 days. Fifteen patients reported 63 Adverse Drug Reactions (ADRs); the most
      common were headache (10 patients), vomiting (6 patients) and pyrexia (5
      patients). Five of these ADRs were considered serious, one patient had three
      concurrent Serious Adverse Events (SAEs); these were vomiting, dehydration and
      headache. Two other patients each had one SAE (headache). There were no
      unexpected Adverse Events (AEs) or thromboembolic episodes and no significant
      changes in vital signs, biochemical, haematological and virology results.
      CONCLUSION: Gammaplex achieved a very high concentration of serum IgG but was
      well-tolerated and effective in the treatment of ITP with a similar degree of
      efficacy to the pre-determined historical control group and the pre-set
      statistical criteria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00504075 Clinical
      Trials Registry India 000016.

PMID- 24892423
TI  - The association between campylobacteriosis, agriculture and drinking water: a
      case-case study in a region of British Columbia, Canada, 2005-2009.
AB  - We studied the association between drinking water, agriculture and sporadic human
      campylobacteriosis in one region of British Columbia (BC), Canada. We compared
      2992 cases of campylobacteriosis to 4816 cases of other reportable enteric
      diseases in 2005-2009 using multivariate regression. Cases were geocoded and
      assigned drinking water source, rural/urban environment and socioeconomic status
      (SES) according to the location of their residence using geographical information
      systems analysis methods. The odds of campylobacteriosis compared to enteric
      disease controls were higher for individuals serviced by private wells than
      municipal surface water systems (odds ratio 1.4, 95% confidence interval 1.1
      1.8). In rural settings, the odds of campylobacteriosis were higher in November
      (P = 0.014). The odds of campylobacteriosis were higher in individuals aged ?15
      years, especially in those with higher SES. In this region of BC,
      campylobacteriosis risk, compared to other enteric diseases, seems to be mediated
      by vulnerable drinking water sources and rural factors. Consideration should be
      given to further support well-water users and to further study the
      microbiological impact of agriculture on water.

PMID- 24892424
TI  - The effect of zinc and D-penicillamine in a stable human hepatoma ATP7B knockout
      cell line.
AB  - Mutations in the copper (Cu) transporter gene ATP7B, the primary cause of Wilson
      disease (WD), result in high liver Cu and death of hepatocytes. Cu chelators and
      zinc salts are the two most important drugs used in the treatment of WD patients;
      however, the molecular mechanisms of the drugs with regard to ATP7B expression
      have not been determined. A targeted knockout of ATP7B (KO) was established in
      the most widely used human hepatoma cell line, HepG2 for molecular studies of the
      pathogenesis and treatment of the disease. KO cells showed similar growth, Cu
      uptake, release, and gene expression as compared to parental cells. However, in
      the presence of Cu, morphological changes, oxidative stress, apoptosis, and loss
      of viability were observed. Induction of metallothionein (MT1X) after Cu exposure
      was significantly reduced in KO cells. Following zinc treatment, MT1X expression
      was strongly induced and a high percentage of KO cells could be rescued from Cu
      induced toxicity. D-penicillamine treatment had a minor effect on the viability
      of KO cells whereas the parental cell line showed a pronounced improvement.
      Combined treatment displayed a highly synergistic effect in KO cells. The data
      suggest that zinc has a previously unrecognized effect on the viability of
      hepatocytes that lack ATP7B due to a high induction of MT1X expression that
      compensates low gene expression after Cu exposure. A combination therapy that
      simultaneously targets at MT1X induction and Cu chelation improves the overall
      survival of hepatocytes for most efficient therapy of patients having WD. 

PMID- 24892427
TI  - Estimating historical eastern North Pacific blue whale catches using spatial
      calling patterns.
AB  - Blue whales (Balaenoptera musculus) were exploited extensively around the world
      and remain endangered. In the North Pacific their population structure is unclear
      and current status unknown, with the exception of a well-studied eastern North
      Pacific (ENP) population. Despite existing abundance estimates for the ENP
      population, it is difficult to estimate pre-exploitation abundance levels and
      gauge their recovery because historical catches of the ENP population are
      difficult to separate from catches of other populations in the North Pacific. We
      collated previously unreported Soviet catches and combined these with known
      catches to form the most current estimates of North Pacific blue whale catches.
      We split these conflated catches using recorded acoustic calls from throughout
      the North Pacific, the knowledge that the ENP population produces a different
      call than blue whales in the western North Pacific (WNP). The catches were split
      by estimating spatiotemporal occurrence of blue whales with generalized additive
      models fitted to acoustic call patterns, which predict the probability a catch
      belonged to the ENP population based on the proportion of calls of each
      population recorded by latitude, longitude, and month. When applied to the
      conflated historical catches, which totaled 9,773, we estimate that ENP blue
      whale catches totaled 3,411 (95% range 2,593 to 4,114) from 1905-1971, and
      amounted to 35% (95% range 27% to 42%) of all catches in the North Pacific. Thus
      most catches in the North Pacific were for WNP blue whales, totaling 6,362 (95%
      range 5,659 to 7,180). The uncertainty in the acoustic data influence the results
      substantially more than uncertainty in catch locations and dates, but the results
      are fairly insensitive to the ecological assumptions made in the analysis. The
      results of this study provide information for future studies investigating the
      recovery of these populations and the impact of continuing and future sources of
      anthropogenic mortality. 

PMID- 24892425
TI  - Macrophage colony-stimulating factor augments Tie2-expressing monocyte
      differentiation, angiogenic function, and recruitment in a mouse model of breast
      cancer.
AB  - Reports demonstrate the role of M-CSF (CSF1) in tumor progression in mouse models
      as well as the prognostic value of macrophage numbers in breast cancer patients.
      Recently, a subset of CD14+ monocytes expressing the Tie2 receptor, once thought
      to be predominantly expressed on endothelial cells, has been characterized. We
      hypothesized that increased levels of CSF1 in breast tumors can regulate
      differentiation of Tie2- monocytes to a Tie2+ phenotype. We treated CD14+ human
      monocytes with CSF1 and found a significant increase in CD14+/Tie2+ positivity.
      To understand if CSF1-induced Tie2 expression on these cells improved their
      migratory ability, we pre-treated CD14+ monocytes with CSF1 and used Boyden
      chemotaxis chambers to observe enhanced response to angiopoietin-2 (ANG2), the
      chemotactic ligand for the Tie2 receptor. We found that CSF1 pre-treatment
      significantly augmented chemotaxis and that Tie2 receptor upregulation was
      responsible as siRNA targeting Tie2 receptor abrogated this effect. To understand
      any augmented angiogenic effect produced by treating these cells with CSF1, we
      cultured human umbilical vein endothelial cells (HUVECs) with conditioned
      supernatants from CSF1-pre-treated CD14+ monocytes for a tube formation assay.
      While supernatants from CSF1-pre-treated TEMs increased HUVEC branching, a
      neutralizing antibody against the CSF1R abrogated this activity, as did siRNA
      against the Tie2 receptor. To test our hypothesis in vivo, we treated PyMT tumor
      bearing mice with CSF1 and observed an expansion in the TEM population relative
      to total F4/80+ cells, which resulted in increased angiogenesis. Investigation
      into the mechanism of Tie2 receptor upregulation on CD14+ monocytes by CSF1
      revealed a synergistic contribution from the PI3 kinase and HIF pathways as the
      PI3 kinase inhibitor LY294002, as well as HIF-1alpha-deficient macrophages
      differentiated from the bone marrow of HIF-1alphafl/fl/LysMcre mice, diminished
      CSF1-stimulated Tie2 receptor expression. 

PMID- 24892426
TI  - The effectiveness of electronic screening and brief intervention for reducing
      levels of alcohol consumption: a systematic review and meta-analysis.
AB  - BACKGROUND: Electronic screening and brief intervention (eSBI) has been shown to
      reduce alcohol consumption, but its effectiveness over time has not been subject
      to meta-analysis. OBJECTIVE: The current study aims to conduct a systematic
      review and meta-analysis of the available literature to determine the
      effectiveness of eSBI over time in nontreatment-seeking hazardous/harmful
      drinkers. METHODS: A systematic review and meta-analysis of relevant studies
      identified through searching the electronic databases PsychINFO, Medline, and
      EMBASE in May 2013. Two members of the study team independently screened studies
      for inclusion criteria and extracted data. Studies reporting data that could be
      transformed into grams of ethanol per week were included in the meta-analysis.
      The mean difference in grams of ethanol per week between eSBI and control groups
      was weighted using the random-effects method based on the inverse-variance
      approach to control for differences in sample size between studies. RESULTS:
      There was a statistically significant mean difference in grams of ethanol
      consumed per week between those receiving an eSBI versus controls at up to 3
      months (mean difference -32.74, 95% CI -56.80 to -8.68, z=2.67, P=.01), 3 to less
      than 6 months (mean difference -17.33, 95% CI -31.82 to -2.84, z=2.34, P=.02),
      and from 6 months to less than 12 months follow-up (mean difference -14.91, 95%
      CI -25.56 to -4.26, z=2.74, P=.01). No statistically significant difference was
      found at a follow-up period of 12 months or greater (mean difference -7.46, 95%
      CI -25.34 to 10.43, z=0.82, P=.41). CONCLUSIONS: A significant reduction in
      weekly alcohol consumption between intervention and control conditions was
      demonstrated between 3 months and less than 12 months follow-up indicating eSBI
      is an effective intervention.

PMID- 24892428
TI  - The complete mitochondrial genome of Meloidogyne graminicola (Tylenchina): a
      unique gene arrangement and its phylogenetic implications.
AB  - Meloidogyne graminicola is one of the most economically important plant parasitic
      nematodes (PPNs). In the present study, we determined the complete mitochondrial
      (mt) DNA genome sequence of this plant pathogen. Compared with other PPNs genera,
      this genome (19,589 bp) is only slightly smaller than that of Pratylenchus vulnus
      (21,656 bp). The nucleotide composition of the whole mtDNA sequence of M.
      graminicola is significantly biased toward A and T, with T being the most favored
      nucleotide and C being the least favored. The A+T content of the entire genome is
      83.51%. The mt genome of M. graminicola contains 36 genes (lacking atp8) that are
      transcribed in the same direction. The gene arrangement of the mt genome of M.
      graminicola is unique. A total of 21 out of 22 tRNAs possess a DHU loop only,
      while tRNASer(AGN) lacks a DHU loop. The two large noncoding regions (2,031 bp
      and 5,063 bp) are disrupted by tRNASer(UCN). Phylogenetic analysis based on
      concatenated amino acid sequences of 12 protein-coding genes support the
      monophylies of the three orders Rhabditida, Mermithida and Trichinellida, the
      suborder Rhabditina and the three infraorders Spiruromorpha, Oxyuridomorpha and
      Ascaridomorpha, but do not support the monophylies of the two suborders Spirurina
      and Tylenchina, and the three infraorders Rhabditomorpha, Panagrolaimomorpha and
      Tylenchomorpha. The four Tylenchomorpha species including M. graminicola, P.
      vulnus, H. glycines and R. similis from the superfamily Tylenchoidea are placed
      within a well-supported monophyletic clade, but far from the other two
      Tylenchomorpha species B. xylophilus and B. mucronatus of Aphelenchoidea. In the
      clade of Tylenchoidea, M. graminicola is sister to P. vulnus, and H. glycines is
      sister to R. similis, which suggests root-knot nematodes has a closer
      relationship to Pratylenchidae nematodes than to cyst nematodes. 

PMID- 24892429
TI  - New mitochondrial and nuclear evidences support recent demographic expansion and
      an atypical phylogeographic pattern in the spittlebug Philaenus spumarius
      (Hemiptera, Aphrophoridae).
AB  - Philaenus spumarius is a widespread insect species in the Holarctic region. Here,
      by focusing on the mtDNA gene COI but also using the COII and Cyt b genes and the
      nuclear gene EF-1alpha, we tried to explain how and when its current
      biogeographic pattern evolved by providing time estimates of the main demographic
      and evolutionary events and investigating its colonization patterns in and out of
      Eurasia. Evidence of recent divergence and expansion events at less than 0.5 Ma
      ago indicate that climate fluctuations in the Mid-Late Pleistocene were important
      in shaping the current phylogeographic pattern of the species. Data support a
      first split and differentiation of P. spumarius into two main mitochondrial
      lineages: the "western", in the Mediterranean region and the "eastern", in
      Anatolia/Caucasus. It also supports a following differentiation of the "western"
      lineage into two sub-lineages: the "western-Mediterranean", in Iberia and the
      "eastern-Mediterranean" in the Balkans. The recent pattern seems to result from
      postglacial range expansion from Iberia and Caucasus/Anatolia, thus not following
      one of the four common paradigms. Unexpected patterns of recent gene-flow events
      between Mediterranean peninsulas, a close relationship between Iberia and North
      Africa, as well as high levels of genetic diversity being maintained in northern
      Europe were found. The mitochondrial pattern does not exactly match to the
      nuclear pattern suggesting that the current biogeographic pattern of P. spumarius
      may be the result of both secondary admixture and incomplete lineage sorting. The
      hypothesis of recent colonization of North America from both western and northern
      Europe is corroborated by our data and probably resulted from accidental human
      translocations. A probable British origin for the populations of the Azores and
      New Zealand was revealed, however, for the Azores the distribution of populations
      in high altitude native forests is somewhat puzzling and may imply a natural
      colonization of the archipelago. 

PMID- 24892432
TI  - The impact of under-recording on cervical cancer-related mortality rates in
      Colombia: an equity analysis involving comparison by provenance.
AB  - OBJECTIVE: Comparing cervical cancer mortality rates in Colombian departments, as
      well as in urban and rural areas and examining the potential causes of any
      differences. METHODOLOGY: This was an ecologic study. Mortality due to cervical
      cancer was estimated from data collected between 2005 and 2008 by the Colombian
      National Statistics Bureau (DANE).This included overall mortality in Colombia,
      mortality by department and mortality by rural and urban area. DANE provided the
      under-recording indicator for mortality by departments and the unmet basic needs
      index. Spearman correlation coefficient was estimated for average mortality by
      department, unmet basic needs and under-recording variables. RESULTS: The overall
      annual mortality rate from 2005 to 2008 due to cervical cancer in Colombia ranged
      from 10 to 11.1 per 100,000 females. Mortality reported in urban areas was higher
      than in rural areas (10.3-11.7 cf 7.6-8.7). The lowest average mortality was
      reported from the Choco department (4.7) and the highest from Meta (18.2). An
      inverse correlation was found between average mortality by department and unmet
      basic needs. The 'under-reporting' indicator had an inverse correlation with
      mortality, meaning that departments having recording issues also reported lower
      mortality rates. CONCLUSIONS: Health systems must adopt strategies designed to
      improve information systems for supporting decision-making and optimise the use
      of health resources, particularly for vulnerable populations and populations
      having unmet basic needs. Comparing mortality amongst departments and areas will
      not lead to reliable conclusions in such under-recording conditions.

PMID- 24892431
TI  - [Perceived health status of people from the central region of Colombia: National
      Health Survey, 2007].
AB  - OBJECTIVE: Determining perceived health status profiles for people aged 6 to 69
      years old from the central region of Colombia, based on the 2007 National Health
      Survey. METHOD: The survey involved 18,683 people aged 6 to 69 years old from the
      central region of Colombia. Descriptive statistics and multiple correspondence
      analyses by sub-region were calculated. Significant variables (<= 0.05 t-test)
      for constructing Cartesian plane factor axes were gender, age, educational level,
      residential area, ethnicity, morbid event reporting and self-perceived health
      status. RESULTS: Three health status typologies were identified: perceived health
      corresponding to socio-demographic characteristics, morbid event reporting and
      residential area. People having a job or engaging in academic activities had
      better health status perception. Indigenous people living in rural areas reported
      injuries arising from an accident, violence and/or poisoning more frequently than
      white people living in urban areas. An educated woman had a more negative
      evaluation of their health status. Agreement was also found for a specific health
      profile and each sub-region being studied. CONCLUSIONS: Differences may have been
      due to self-care, social service access, geographic accessibility and cultural
      patterns regarding self-reported health status perception. Analyzing greater
      depth is needed.

PMID- 24892430
TI  - Suboptimal vitamin D status in a population-based study of Asian children:
      prevalence and relation to allergic diseases and atopy.
AB  - BACKGROUND: New evidence shows high prevalence of vitamin D deficiency in many
      countries and some studies suggest a possible link between vitamin D status and
      allergic diseases. The objectives of this study were to determine the prevalence
      of suboptimal vitamin D status in a population sample of Asian children and to
      investigate the relationship of vitamin D status with allergic diseases and
      atopy. METHODS: Children aged 5-18 years (N = 1315) in the Prediction of
      Allergies in Taiwanese CHildren (PATCH) study were evaluated using
      questionnaires, anthropometric measurements, and serum levels of 25
      hydroxyvitamin D [25(OH)D] and total and specific immunoglobulin E (IgE).
      RESULTS: The mean concentration of serum 25(OH)D was 20.4 ng/mL (SD: 7.1 ng/mL).
      Vitamin D deficiency (defined as serum 25(OH)D<20 ng/mL) was present in 670
      subjects (51.0%), while vitamin D insufficiency (defined as serum 25(OH)D<30
      ng/mL) was observed in 1187 subjects (90.3%). Older age (P<0.001), female gender
      (P<0.001), higher body mass index (P = 0.001), winter and spring seasons
      (compared to summer; P both<0.001), and passive smoking (P = 0.011) were
      independently associated with low serum 25(OH)D levels. After adjusting for
      potential confounders, serum 25(OH)D status had no association with asthma,
      rhinitis, eczema, atopy, or total serum IgE (all P>0.05). CONCLUSIONS: Low serum
      25(OH)D levels are remarkably common in this population sample of Asian children,
      suggesting that millions of children living in Taiwan may have suboptimal levels
      of vitamin D, which should be a matter of public health concern. Our results
      provides epidemiological evidence against the association of vitamin D status
      with various allergic diseases and atopy in Asian children.

PMID- 24892433
TI  - [Older women associating obesity with a negative perception of their health: a
      study in low-income neighborhoods in Curitiba, southern Brazil].
AB  - OBJECTIVE: The present study was aimed at analyzing the association between
      elderly women's perception of their nutritional status (overweight and obesity)
      regarding their overall health in low-income neighborhoods in Curitiba, Brazil.
      METHODS: The sample consisted of 449 elderly women participating in the Idoso em
      Movimento program in low-income neighborhoods in Curitiba. Body weight and height
      were measured to calculate their Body Mass Index (BMI); 25 kg/m(2) and 30 kg/m(2)
      cut-off points were considered for determining weight status regarding being
      overweight and obese, respectively. A specific question concerning elderly health
      perception was used for classifying them into negative or positive health
      perception categories. Kruskal-Wallis and Chi-square tests were used for data
      analysis in terms of descriptive statistics. Binary logistic regression was used
      for analyzing the association between weight status and health perception,
      controlling for age, economic status, marital status, years spent in formal
      education, occupational status and time spent on physical activity per week. A 5
      % significance level was used. RESULTS: Obesity was significantly associated with
      a perception of suffering negative health (p<0.05). Obese elderly women were
      twice as likely to have a negative perception of their health. Being overweight
      was not associated with a negative perception of health. CONCLUSION: Decreasing
      obesity in obese low-income elderly is paramount for promoting better health
      perception in this risk group.

PMID- 24892434
TI  - Current professional practice in Brazilian mental healthcare services.
AB  - OBJECTIVE: Mental health reform in Brazil presupposes mental health becoming
      integrated into the Brazilian health system, involving multidisciplinary teams
      whose professional practice has yet to be defined. The present study forms part
      of a project aimed at understanding human resources practices in Brazilian mental
      healthcare services. METHODS: This was a descriptive, exploratory study using a
      sample of highly qualified practitioners involved in the Ribeirao Preto/SP public
      mental health network. The project was approved by the Ribeirao Preto College of
      Nursing/University of Sao Paulo's ethics committee. A semi-structured
      questionnaire was used and the data was statistically analyzed. RESULTS: One
      hundred and forty-four of the 193 practitioners from the 8 public mental and
      psychiatric health care services agreed to participate. It was observed that
      current practice was mainly based on individual care, emphasizing medical,
      psychological and nursing care. Group activities were more frequently provided by
      community services. CONCLUSION: Mental care was infrequently prescribed and a low
      value was placed on activities like observation, recording and therapeutic
      interaction. Mental care services were being structured; however, practitioners
      still had difficulties in implementing current policy.

PMID- 24892435
TI  - [Healthcare patterns and life styles in adolescents from three schools in
      Popayan, Colombia].
AB  - OBJECTIVE: Identifying healthy practice and risky behavior in students from
      Popayan in June and December 2009. METHOD: This was across-sectional study in 3
      schools in Popayan. The information was collected using the Global School Health
      Survey (GSHS), validated by the WHO. RESULTS: The results showed that 55.2 % of
      teenagers tried smoking for the first time between 10 and 12 years of age. The
      single largest group regarding trying/starting to drink alcohol was 13 to 15
      years of age. Episodes of solitude were experienced around 14 years of age and
      the early onset of sexual activity was concerning. CONCLUSION: The results
      confirmed the presence of risk factors for chronic diseases, violence and HIV
      infection in this study population.

PMID- 24892436
TI  - [Patients being transported by civil airline companies].
AB  - OBJECTIVE: Colombian aviation operations began in 1919; however, no knowledge is
      currently available concerning medical air transport in the country. This study
      involved local companies in Bogota which provided air medical transfer for
      patients from 2005 to 2007; it was aimed at improving knowledge regarding air
      transport for patients in Colombia. METHOD: This was a descriptive study of
      patient air transfer by three companies during the aforementioned three-year
      period. The Risk Score for Transport Patients' (RSTP) scale was used in each
      report. RESULTS: Only three companies authorized access to their medical reports;
      98 reports were found, 24 in 2005, 28 in 2006 and 46 in 2007 but only 96 patients
      were transferred because two flights were cancelled because of the patients' poor
      medical condition. All the records dealt with secondary air transfer (between
      facilities) in fixed-wing aircraft. 61 % of the patients so transferred were male
      and 38 % female; 51 % were adults and 49 % were less than 18 years old (57 % of
      the latter being newborn). According to the RSTP scale, 27 % of the patients were
      unstable, 48 % moderately unstable and 25 % were stable. 90 % of the transfers
      were accompanied by medical staff, 14 cases had complications during their
      flights but mortality was just 4 %. CONCLUSION: Patients' air transfer requires
      complete assessment and a complete record of all the variables related to
      transporting patients by air and personnel trained in dealing with critically-ill
      patients of all ages.

PMID- 24892437
TI  - [Congenital syphilis incidence disparities in Colombia 2005 to 2011: an
      ecological study].
AB  - OBJECTIVE: Syphilis is a systemic, infecto-contagious, sexually-transmitted
      disease caused by the spirochete bacterium Treponema pallidum. Interventions
      reducing congenital syphilis incidence represent two of the Millennium
      Development Goals (MDG). Diagnostic and treatment methods are available for
      managing congenital syphilis; even so, variations occur in seroprevalence and the
      number of annual cases worldwide, so the situation continues to be worrying. This
      study was aimed at describing disparities per department regarding congenital
      syphilis incidence in Colombia from 2005 to 2011. METHODOLOGY: Colombian
      Institute of Health (Instituto Nacional de Salud-INS) surveillance system records
      and Colombian Statistics Department (Departamento Administrativo Nacional de
      Estadistica-DANE) records of live births (LB) and basic unsatisfied needs (BUN)
      from 2005 to 2011 were analyzed. Results Overall incidence in Colombia rose from
      2.15 cases per 1,000 LB in 2005, (1,550 cases) to 3.28 cases per 1,000 LB in 2011
      (2,078 cases), thereby moving further away from the MDG (0.5 per 1,000 LB).
      CONCLUSIONS: The growing number of cases of congenital syphilis indicates that
      this continues being a priority problem for public health and that the Overall
      Healthcare-related Social Security System (OHSSS) has not been able to resolve
      it, in spite of increased coverage and the resources which this entity has
      received during the last few years. Such situation demands a re-evaluation of the
      OHSSS's real impact on public healthcare results.

PMID- 24892438
TI  - [Dengue-related hepatic compromise in children from the Huila department of
      Colombia].
AB  - OBJECTIVE: Dengue is the most important arthropod-borne viral disease in the
      world; it can be life-threatening because of liver involvement. Aim Determining
      liver involvement frequency and severity in dengue-infected children. METHODS:
      This was a descriptive case series study which involved studying 108 dengue
      infected children aged less than 13 years old whose infection had been confirmed
      by the detection of dengue-specific IgM and NS1 in plasma. Clinical and
      biochemical parameters were used for evaluating liver involvement, including
      transaminases and albumin. Hepatitis A and leptospira infection were also
      evaluated by using ELISA to detect pathogen-specific IgM in plasma during acute
      and convalescence phases. The study was carried out at a teaching hospital in
      Neiva from June 2009 to May 2010. RESULTS: Ninety-eight of the aforementioned
      cases were clinically classified as dengue with warning signs (DWS) and 10 as
      severe dengue (SD). Two out of three DWS patients and all SD patients had some
      degree of liver involvement, shown clinically and biochemically. Regardless of
      the clinical classification, hepatomegaly was the main clinical sign of liver
      involvement and was present in 85% of all the children in the study. It is worth
      noting that 5 patients had probable dengue and leptospirosis co-infection, this
      being the first instance of this in Colombia. None of the cases analyzed here had
      acute hepatitis A. CONCLUSIONS: Liver compromise should be considered in
      confirmed cases of dengue as shown in this series of children. Leptospirosis must
      be considered as differential diagnosis and also as causing co-infection in a
      febrile child.

PMID- 24892439
TI  - [The responsiveness of males having suffered forced displacement regarding their
      risk of contracting sexually-transmitted infection].
AB  - OBJECTIVE: Describing displaced males' responsiveness regarding issues concerning
      sexual and reproductive health, particularly contracting STI/HIV/AIDS.
      METHODOLOGY: An ethnographic study concerning displaced males who were living in
      shelters was carried out in Medellin, Colombia, from March to November 2010;
      observation and semi-structured interview techniques were used. Nineteen men(with
      and without a partner) aged 18 to 60 years old were interviewed; they had been
      suffering the effects of forced displacement for less than 1 year. The results
      were analyzed following grounded theory guidelines. RESULTS: Three main
      categories were analyzed: having been forcibly displaced and such impact on their
      daily life, issues related to their sexuality and their ability to respond.
      Despite forcibly displaced male shaving information about condo muse and
      perceiving the risk posed by STI/HIV/AIDS, they did not take preventative
      measures when engaging in their sexual practices and most assumed various risky
      behavior patterns. Living conditions in the hostel, few job opportunities and the
      culture regarding machismo increased the risk of acquiring an STI and decreased
      their responsiveness to them. CONCLUSION: Responsiveness to STI/HIV/AID Sin males
      who had been experiencing the hardships of having been recently displaced was
      seen to have become reduced because of the material and psychosocial conditions
      which they had to face. Policies and programs addressing this group's specific
      needs are required which are aimed at improving information regarding sexual and
      reproductive health, access to services and opportunities for decent work.

PMID- 24892440
TI  - [Overall pattern of accidents caused by poisonous animals in Colombia, 2006
      2010].
AB  - OBJECTIVE: This study was motivated as only partial knowledge is available
      (regarding national statistics) about accidents caused by poisonous animals in
      Colombia. The study was aimed at establishing a base-line concerning accidents
      reported by phone to the Toxicology Management and Research Information Centre
      (CIGITOX) from all over Colombia; such data was taken from the centre's data-base
      following its five years of being in operation(2006-2010). METHODS: This was a
      descriptive, retrospective study, taking information from the CIGITOX database
      over a five-year period (2006-2010); Excel 2011was used for statistical analysis.
      RESULTS: The database contained 1,783 cases which had been reported and attended;
      47 % concerned snake bite accidents (an obligatory report event in Colombia), 25
      % scorpion stings and 11 % spider bites, followed by others having valuable
      epidemiologic representation in the main areas of occurrence, such as the
      Antioquia, Valle del Cauca and Cundinamarca departments. DISCUSSION: The data
      provided an overview of the situation which could lead to promoting public health
      program aimed at raising awareness in communities, institutions and healthcare
      professional's whilst enforcing their ability to respond effectively.

PMID- 24892441
TI  - [Quantifying the chemical composition of crack-cocaine (bazuco) samples seized in
      Colombia during the first half of 2010].
AB  - OBJECTIVES: Quantifying crack-cocaine (known locally as bazuco or smokable
      cocaine base paste-PBC) use and identifying other components in study conditions
      regarding samples of crack-cocaine seized in Colombia and held by the Colombian
      Institute of Legal Medicine and Forensic Science Narcotics Laboratory in Bogota
      during the first half of 2010. METHODS: A cross-sectional, exploratory analytical
      study was carried out for chemically characterizing crack-cocaine samples by the
      gas chromatography analytical methodology using ion trap mass spectrometry
      developed and validated in the Universidad National de Colombia's Medicine
      Faculty's Toxicology Laboratory in Bogota. RESULTS: A 4 % to 70 % w/w cocaine
      base concentration was found in the 109 samples tested (37 % w/w mean); 73 % of
      the samples had 20 % to 50 % w/w concentration. Other coca alkaloids were
      identified, such astropacocaine, trans-cinnamoylcocaine, norcocaine and ecgonine
      methyl ester. Caffeine was identified as an adulterantin 57 % of the samples and
      phenacetin in 2.8 % of them. DISCUSSION: The toxicological significance of the
      results concerning crack-cocaine consumers was quantified, given the profile for
      chronic users.

PMID- 24892442
TI  - [Ways of evaluating Latin-American initiatives for promoting breastfeeding].
AB  - This work has analyzed the different methods used since the 1990s for evaluating
      initiatives aimed at promoting breastfeeding in Latin-America. A review was made
      of the pertinent literature using a protocol based on researching, selecting and
      analyzing different ways of making such evaluation. Fifty-eight evaluations were
      selected for study and comparison. It is worth noting that the most commonly used
      types of evaluation concerned initiative effectiveness and impact; assessment was
      particularly aimed at educational or breastfeeding counseling programs.
      Evaluation also concerned initiatives encompassing two or three healthcare
      promotion strategies related to developing personal skills and the reorientation
      of healthcare services. The results provided an overview of the way initiatives
      promoting breastfeeding have been evaluated related to the pertinent literature
      regarding how healthcare promotion is evaluated. 

PMID- 24892443
TI  - [The body as the scenario for social vulnerability regarding health].
AB  - Theoretical reflection concerning the human body within a scenario of social
      healthcare practices recognizes its nature through ontological dimensions for
      defining our finiteness and facticity in a world where nobody experiences their
      own birth or death but rather experiences such events through others. Considering
      health as an overall process called existence, being conscious of one's own body
      in terms of dynamic states of health and disease, is related to scenarios where
      the body has played a central role in the existential experience of the culture
      which it has built and in which it has been living, as well as in the
      relationship of knowledge with how power is exercised. Relationships between
      knowledge, power, resistance and the action of bodies are scenarios concerning
      social vulnerability regarding health. We wish to raise awareness concerning the
      relationship between bodies and social vulnerability regarding health as an
      emergent scenario for promoting discussion dealing with claiming the right to
      health and the chances of it being positively affected by public health policy
      from a trans-sector response and a community-based response proposed by Colombian
      society and culture. 

PMID- 24892444
TI  - [Agreement between adolescents' self-perceived weight and body mass index (BMI)].
AB  - OBJECTIVE: Determining agreement between adolescent students' self-perceived
      weight and body mass index (BMI) in Bogota, Colombia. METHOD: This was
      exploratory research in which a group of 321 12-18 year-old (mean=14.4; SD=1.6)
      adolescent students participated: 206 girls and 115 boys. Agreement between self
      perceived weight (0=low, 1=adequate and 2=high) and BMI was estimated using
      Spearman's correlation (r s); the authors' expected r s was higher than 0.6.
      RESULTS: It was found that self-perceived weight was low in 48 students (15.0 %),
      adequate in 228 (71.0 %) and high in 45 of them (14.0 %). BMI ranged from 14.5 to
      29.8 (mean=20.5; SD=3.0). Overall r s was 0.4 amongst boys and girls, 0.5 in
      girls and 0.3 in boys. CONCLUSIONS: Agreement was low between the adolescents'
      self-perceived weight and their actual BMI; these measurements were not
      interchangeable. Further research is needed to corroborate the findings.

PMID- 24892445
TI  - BI-69A11 enhances susceptibility of colon cancer cells to mda-7/IL-24-induced
      growth inhibition by targeting Akt.
AB  - BACKGROUND: Akt and its downstream signalling pathways contribute to the
      aetiology and progression of colorectal carcinoma (CRC). Targeting the Akt
      pathway is an attractive strategy but few chemotherapeutic drugs have been used
      to treat CRC with only limited success. BI-69A11, a small molecule inhibitor of
      Akt, efficiently inhibits growth in melanoma cells. Melanoma differentiation
      associated gene-7 (mda-7)/interleukin-24 promotes cancer-selective apoptosis when
      delivered by a tropism-modified replication incompetent adenovirus (Ad.5/3-mda
      7). However, Ad.5/3-mda-7 displays diminished antitumour efficacy in several CRC
      cell lines, which correlates with the expression of K-RAS. METHODS: The
      individual and combinatorial effect of BI-69A11 and Ad.5/3-mda-7 in vitro was
      studied by cell viability, cell cycle, apoptosis and invasion assays in HT29 and
      HCT116 cells containing wild type or mutant K-ras, respectively. In vivo HT29
      tumour xenografts were used to test the efficacy of the combination treatment.
      RESULTS: BI-69A11 inhibited growth and induced apoptosis in CRC. However,
      combinatorial treatment was more effective compared with single treatment. This
      combination showed profound antitumour and anti angiogenic effects in vitro and
      in vivo by downregulating Akt activity. CONCLUSIONS: BI-69A11 enhances the
      antitumour efficacy of Ad.5/3-mda-7 on CRC overexpressing K-RAS by inducing
      apoptosis and regulating Akt activity thereby warranting further evaluation in
      treating CRC.

PMID- 24892446
TI  - Prognostic significance of AMPK activation in advanced stage colorectal cancer
      treated with chemotherapy plus bevacizumab.
AB  - BACKGROUND: AMP-activated protein kinase (AMPK) has a central role in cellular
      energy sensing and is activated in preclinical tumour models following anti
      vascular endothelial growth factor (VEGF) therapy. The possible predictive or
      prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs
      has not been investigated so far. METHODS: Expression of components of the AMPK
      pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa
      carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by
      immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus
      bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK
      pathway scores and clinico-pathological characteristics were assessed. Overall
      survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios
      were computed to identify prognostic factors. RESULTS: Fourteen patients (29.2%)
      were included in the pAMPK-negative group (score <=5), whereas 34 patients
      (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's
      coefficient for the correlation between pAMPK and pACC scores in primary tumour
      samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P
      value 0.0002) but not with PFS, whereas low pACC levels were associated both with
      worse OS and PFS (P-value 0.0007 and 0.01, respectively). CONCLUSIONS: Our
      findings suggest that high tissue AMPK activation is a prognostic biomarker in
      this cohort of metastatic colorectal cancer patients.

PMID- 24892447
TI  - Improving decision making about clinical trial participation - a randomised
      controlled trial of a decision aid for women considering participation in the
      IBIS-II breast cancer prevention trial.
AB  - BACKGROUND: Decision aids may improve informed consent in clinical trial
      recruitment, but have not been evaluated in this context. This study investigated
      whether decision aids (DAs) can reduce decisional difficulties among women
      considering participation in the International Breast Cancer Intervention Study
      II (IBIS-II) trial. METHODS: The IBIS-II trial investigated breast cancer
      prevention with anastrazole in two cohorts: women with increased risk
      (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia,
      New Zealand and United Kingdom participants were randomised to receive a DA (DA
      group) or standard trial consent materials (control group). Questionnaires were
      completed after deciding about participation in IBIS-II (post decision) and 3
      months later (follow-up). RESULTS: Data from 112 Prevention and 34 DCIS
      participants were analysed post decision (73 DA; 73 control); 95 Prevention and
      24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no
      effect on the primary outcome of decisional conflict. The DCIS-DA group had
      higher knowledge post decision, and the Prevention-DA group had lower decisional
      regret at follow-up. CONCLUSIONS: This was the first study to evaluate a DA in
      the clinical trial setting. The results suggest DAs can potentially increase
      knowledge and reduce decisional regret about clinical trial participation.

PMID- 24892450
TI  - International accreditation and quality medical education.

PMID- 24892448
TI  - Dichloroacetate induces autophagy in colorectal cancer cells and tumours.
AB  - BACKGROUND: Dichloroacetate (DCA) has been found to have antitumour properties.
      METHODS: We investigated the cellular and metabolic responses to DCA treatment
      and recovery in human colorectal (HT29, HCT116 WT and HCT116 Bax-ko), prostate
      carcinoma cells (PC3) and HT29 xenografts by flow cytometry, western blotting,
      electron microscopy, (1)H and hyperpolarised (13)C-magnetic resonance
      spectroscopy. RESULTS: Increased expression of the autophagy markers LC3B II was
      observed following DCA treatment both in vitro and in vivo. We observed increased
      production of reactive oxygen species (ROS) and mTOR inhibition (decreased pS6
      ribosomal protein and p4E-BP1 expression) as well as increased expression of MCT1
      following DCA treatment. Steady-state lactate excretion and the apparent
      hyperpolarised [1-(13)C] pyruvate-to-lactate exchange rate (k(PL)) were decreased
      in DCA-treated cells, along with increased NAD(+)/NADH ratios and NAD(+). Steady
      state lactate excretion and k(PL) returned to, or exceeded, control levels in
      cells recovered from DCA treatment, accompanied by increased NAD(+) and NADH.
      Reduced k(PL) with DCA treatment was found in HT29 tumour xenografts in vivo.
      CONCLUSIONS: DCA induces autophagy in cancer cells accompanied by ROS production
      and mTOR inhibition, reduced lactate excretion, reduced k(PL) and increased
      NAD(+)/NADH ratio. The observed cellular and metabolic changes recover on
      cessation of treatment.

PMID- 24892449
TI  - Endothelial CD276 (B7-H3) expression is increased in human malignancies and
      distinguishes between normal and tumour-derived circulating endothelial cells.
AB  - BACKGROUND: Mature circulating endothelial cells (CEC) are surrogate markers of
      endothelial damage. CEC measured in patients with advanced cancer are thought not
      only to derive from damaged normal vasculature (n-CEC), but also from damaged (t
      CEC). Therefore, assays that allow the discrimination between these two putative
      types of CEC are thought to improve the specificity of the enumeration of CEC in
      cancer. METHODS: Identification of tumour-associated endothelial markers (TEM) by
      comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC
      in peripheral blood of cancer patients by incorporating TEM in our novel flow
      cytometry-based CEC detection assay. RESULTS: No difference in antigen expression
      between normal and malignant endothelial cells (ECs) was found for CD54, CD109,
      CD137, CD141, CD144 and CXCR7. In contrast, overexpression for CD105, CD146,
      CD276 and CD309 was observed in tumour ECs compared with normal ECs. CD276 was
      most differentially expressed and chosen as a marker for further investigation.
      CD276-expressing CEC were significantly higher in 15 patients with advanced
      colorectal cancer (median 9 (range 1-293 cell per 4 ml); P<0.005), in 83 patients
      with a glioblastoma multiforme (median 10 (range 0-804); P<0.0001) and in 14
      patients with advanced breast cancer (median 14 (range 0-390) P<0.05) as compared
      with 24 healthy individuals (median 3 (range 0-11)). Of all patients with
      malignancies, 58% had CD276(+) CEC counts above the ULN (8 cell per 4 ml).
      CONCLUSIONS: The present study shows that CD276 can be used to discriminate ECs
      from malignant tissue from ECs from normal tissue. In addition, CD276(+) CEC do
      occur in higher frequencies in patients with advanced cancer.

PMID- 24892451
TI  - HIV sexual risk behaviors in youth 15-24 years of age in Cali, Colombia: Do
      differences exist among neighborhoods?
AB  - INTRODUCTION: HIV/AIDS is a global health priority. About 40% of new infections
      occur among heterosexual youth by means of sexual contact. In Cali, district 13,
      15 and 20 account for 11.5% of the prevalent cases and 18.0% of incident cases.
      OBJECTIVE: To establish differences in risk behaviors for HIV among young people
      15-24 yrs of age from two areas of Cali, Colombia. METHODS: We carried out a
      cross-sectional study among young people between 15 and 24 yrs of age in these
      districts. The selection was done with a two-stage probability sampling. We
      estimated the prevalence of sexual relationships without condom usage, sex with
      multiple partners, and sex under the effects of alcohol and through logistical
      regression we identified the related factors. RESULTS: In district 13, 15 and 20,
      the prevalence of unprotected sexual relationships in the last 12 months and the
      prevalence of sex with two or more partners was 70%; and 38% of young people had
      sex under the effects of alcohol. In both areas, the intention was positively
      related to the risk behaviors. We found socio-demographic factors, intentions,
      and beliefs that increase the opportunity to display these behaviors. The effect
      of these factors differs by district. CONCLUSIONS: We observed a high prevalence
      of risk behaviors for HIV related to socio-demographic factors, intentions and
      beliefs that warrant interventions appropriate for local realities.

PMID- 24892452
TI  - Association between periodontal disease and plasma levels of cholesterol and
      triglycerides.
AB  - OBJECTIVE: untreated periodontal disease seems to cause low grade systemic
      inflammation and blood lipid alteration leading to increased cardiovascular
      disease risk. To start testing this hypothesis in colombian patients, a
      multicentre study was conducted including the three main state capitals: bogota,
      medellin and cali. METHODS: in this study 192 (28.4%) advanced and 256 (37.8%)
      moderate periodontitis patients were investigated for socio-demographic
      variables, city of precedence, periodontal parameters, smoking, red complex
      periodontopathic bacteria, serum antibodies against porphyromonas gingivalis and
      aggregatibacter actinomycetemcomitans and blood lipids including total
      cholesterol, hdl, ldl and triglycerides (tg). Those parameters were compared to
      229 (33.8%) controls having periodontal health or gingivitis. RESULTS: advanced
      periodontitis had worst periodontal indexes, than moderate periodontitis and
      controls. Interestingly, higher hdl and tg levels were present in periodontitis.
      Bmi <30 and smoking were associated with increased hdl, hdl-35, ldl and tg, while
      glycemia >100 mg/dl associated with hdl, hdl-35 and tg. Tannerella forsythia
      showed a significant association with hdl-35 in bivariate analysis and serum igg1
      against p. Gingivalis associated with hdl-35 and serum igg1 against t. Forsythia
      associated with tg and serum igg2 against a. Actinomycetemcomitans correlated
      with levels of hdl y hdl-35. In logistic regression the periodontitis patients
      from cali presented reduced hdl levels as compared to bogota and medellin
      patients. Presence of igg1 antibodies against p. Gingivalis and a.
      Actinomycetemcomitans correlated with reduced hdl levels. CONCLUSION: this study
      confirmed that untreated periodontitis generates alteration in serum lipid levels
      and systemic bacterial exposure against important periodontopathic bacteria could
      be the biological link.

PMID- 24892453
TI  - Remifentanil at induction of general anesthesia for cesarean section: Double
      blind,randomized clinical trial.
AB  - INTRODUCTION: Remifentanil, with its rapid activity onset and short duration of
      action, may be more effective than other opioids for providing hemodynamic
      stability during obstetric anesthesia. However, there is some evidence of adverse
      effects on neonatal respiratory function. We investigated maternal and fetal
      effects of Remifentanil during cesarean section surgery. METHODS: Eighteen women
      with singleton term pregnancies, and physical class status of I or II as defined
      by the American Society of Anesthesia (ASA), who were undergoing general
      anesthesia for semi-elective cesarean section were randomized into two groups (40
      in each group) that received either an intravenous bolus of 0.5 ug/kg
      Remifentanil or the same dose of saline as a placebo. Maternal hemodynamic
      variables and neonatal umbilical artery pH and Apgar score at first and fifth min
      were evaluated in both groups. RESULTS: Systolic and diastolic blood pressure
      were significantly lower after tracheal intubation and skin incision in the
      Remifentanil group as compared with the control group (p <0.05). There were no
      significant differences regarding heart rate between groups at any time (p >
      0.05). Apgar scores at first and fifth min were not significantly different among
      groups (p>0.05). No neonate required assisted ventilation or naloxan
      administration. CONCLUSION: Remifentanil may be a safe and effective drug for the
      induction of general anesthesia and surgical stimulation without subsequent
      neonatal depression.

PMID- 24892454
TI  - Expression and activation of intracellular receptors TLR7, TLR8 and TLR9 in
      peripheral blood monocytes from HIV-infected patients.
AB  - INTRODUCTION: TLR's play a role in host defense in HIV infection recognizing the
      viral DNA or RNA. Their activation induces a signaling pathway that includes the
      proteins MyD88, IRAK4, TRAF6 and the transcription factor NF-kBp65. OBJECTIVE: To
      determine the expression of TLR7, TLR8 and TLR9, and activation of its signaling
      pathway in monocytes from patients infected with HIV. Methods. Expression of
      TLR7, TLR8 and TLR9 was determined in monocytes from HIV-infected patients (n=
      13) and control subjects (n= 13), which were activated with specific ligands. The
      expression of MyD88 and NF-kBp65 were determined by flow cytometry; IRAK4 and
      TRAF6 were studied by immunoblotting. RESULTS: No statistical difference was
      found in the expression of TLR7, 8 and 9 in monocytes from patients compared to
      controls, but we observed the non-significant increased expression of TLR9 in
      patients. The activation showed no significant difference in the expression of
      MyD88 and NF-kBp65 in patients when compared to controls, but were decreased in
      stimulated cells over non-stimulated cells. IRAK4 and TRAF6 were not detected.
      CONCLUSIONS: No statistical difference was observed in the expression of
      intracellular TLRs, MyD88 and NFkBp65 in monocytes from patients compared to
      controls. This was probably due to effective antiretroviral therapy being
      received at the time of study entry. Additional studies are needed under
      controlled conditions that include infected patients with and without ARVT,
      responders and non-responders, and work with different cell populations.

PMID- 24892455
TI  - Multicentric study of epidemiological and clinical characteristics of persons
      injured in motor vehicle accidents in Medellin, Colombia, 2009-2010.
AB  - INTRODUCTION: Traffic accidents (TA) cause 1.23 million deaths each year
      worldwide while between 20 and 50 million persons are injured each year. In 2011
      in Medellin, Colombia, there were 307 traffic deaths and 23.835 injured with 411
      accidents for each 10.000 vehicles. OBJECTIVE: The purpose of the study was to
      describe the epidemiologic and clinical characteristics, as well as the quality
      of life and disability outcomes for those injured in traffic accidents in
      Medellin. METHODS: This prospective, descriptive, cross-sectional study collected
      data from 834 patients that were classified with the New Injury Severity Score
      (NISS) , the WHO-DAS-II (Disability Assessment) Scale and the SF-36 Health
      Survey. RESULTS: Three-fourths (75.8%) of the patients were male. Eighty-one
      percent (81.0%) of patients were involved in motorcycle accidents, with 45.6%
      suffering moderate trauma, and 32.6% experiencing severe trauma. Of the patients
      with severe trauma, 8.5% were not wearing helmets. Half of the sample (49.7%)
      injured their extremities. The WHODAS-II domains most affected were: Activities
      outside the home (62.0%), Housework (54.3%) and Moving in one's environment
      (45.2%). Quality of life areas affected were: Physical role (20.3%), Body pain
      (37.3%), Emotional role (44.1%), Physical functioning (52.6%). CONCLUSIONS:
      Patients with more severe injuries had higher levels of disability and a worse
      quality of life. Motorcycles made up a large proportion of traffic accidents in
      this city and mitigation strategies to reduce this public health problem should
      particularly focus on this high-risk group.

PMID- 24892456
TI  - Determination of the HER2 amplification status by in situ fluorescent
      hybridization and concordance with immunohistochemistry for breast cancer samples
      in Colombia.
AB  - OBJECTIVES: To determine the status of the HER2 amplification in Breast cancer
      performed in peripheral laboratories in Colombia by immunohistochemistry and its
      comparison with central laboratories and the FISH status. METHODS: Four thousand
      one hundred and five cases referred for the determination of the HER2 status by
      FISH and/or IHQ to the Department of Pathology of the Fundacion Santa Fe were
      studied. The analysis included correlation between the IHQ HER2 score submitted
      by the peripheral laboratory (PL), the HER2 score emitted in the CL and the FISH
      studies performed in the central laboratory (CL). RESULTS: Two thousand five
      hundred and eight HER2 IHQ studies were performed in the (CL), using the Dako
      Herceptest. With the following results: 68.2 % negative (0-1+); 16,4%
      indeterminate (2+); 15.3% 3+ and 2.3 % not adequate. 1360/ 1719 cases studied by
      FISH came from the (PL), and 329 (19.1%) from the (CL). Comparing the IHQ score
      emitted by the PL and the positive FISH status showed: 6/28 0+ were positive (21.
      4%); 7/31 1+ (22. 5%); 397/1240 2+ (32.8%) and 74/91 3+ (81. 3%). In the CL the
      results were 1/9 0+ (11.1%); 3/18 1+ (16.7%); 154/292 2+ (53%); and 9/9 3+
      (100%). Only 1/4 negative cases (0/1+) was in house. CONCLUSION: The false
      negative rate (22%), and false positive results (18.7%), of the HER2 status
      performed by IHQ in peripheral laboratories in Colombia is unacceptable high as
      well as the inadequacy of tissue indicating that pre-analytical factors have to
      be improved in Colombia in order to get optimal results.

PMID- 24892457
TI  - Pigmented Eccrine Poroma in abdominal region, a rare presentation.
AB  - The eccrine poroma or Hidracanthoma Simplex is a rare benign adnexal tumor of
      ephitelial cells, with an incidence of 0.001 to 0.008%1. In two-thirds of the
      patients it appears on the soles and lateral borders of the feet. We report the
      case of a patient with pigmented eccrine poroma in abdominal skin, of a rare
      entity presentation with a single report in the literature in that location. 

PMID- 24892458
TI  - Albendazole-induced liver injury: a case report.
AB  - We report a case of a 47-year-old male, who was referred to the clinical
      hepatology services at Pablo Tobon Uribe Hospital for evaluation of a jaundice
      syndrome. After undergoing several exams, we diagnosed hepatic hydatidosis and
      the patient was treated with albendazole; however, after five months of
      uninterrupted treatment the patient again consulted and his liver test showed
      marked hepatocellular damage. This time, the patient was diagnosed with drug
      induced liver injury due to albendazole, based on information from the clinical
      record, history of drug consumption, clinical and laboratory tests improved after
      discontinuing the medication and after discarding other possible causes; this
      diagnosis was supported by the CIOMS/RUCAM scale, which showed a "likely"
      correlation between hepatocellular damage and drug toxicity etiology. 

PMID- 24892460
TI  - An insider's view of the new diagnostic and statistical manual of North American
      psychiatry (DSM-5).

PMID- 24892459
TI  - Malaria vaccines: high-throughput tools for antigens discovery with potential for
      their development.
AB  - Malaria is a disease induced by parasites of the Plasmodium genus, which are
      transmitted by Anopheles mosquitoes and represents a great socio-economic burden
      Worldwide. Plasmodium vivax is the second species of malaria Worldwide, but it is
      the most prevalent in Latin America and other regions of the planet. It is
      currently considered that vaccines represent a cost-effective strategy for
      controlling transmissible diseases and could complement other malaria control
      measures; however, the chemical and immunological complexity of the parasite has
      hindered development of effective vaccines. Recent availability of several
      genomes of Plasmodium species, as well as bioinformatic tools are allowing the
      selection of large numbers of proteins and analysis of their immune potential.
      Herein, we review recently developed strategies for discovery of novel antigens
      with potential for malaria vaccine development. 

PMID- 24892463
TI  - Diabetes guidelines may delay timely adjustments during treatment and might
      contribute to clinical inertia.
AB  - Clinical inertia and poor knowledge by many physicians play an important role in
      delaying diabetes control. Among other guidelines, the Position Statement of the
      American Diabetes Association/European Association for the Study of Diabetes on
      Management of Hyperglycemia in Type 2 Diabetes is a respected guideline with high
      impact on this subject in terms of influencing physicians in the definition of
      strategic approach to overcome poor glycemic control. But, on the other hand, it
      carries a recommendation that might contribute to clinical inertia because it can
      delay the needed implementation of more vigorous, intensive, and effective
      strategies to overcome poor glycemic control within a reasonable time frame
      during the evolution of the disease. The same is true with other respected
      algorithms from different diabetes associations. Together with pharmacological
      interventions, diabetes education and more intensive blood glucose monitoring in
      the initial phases after the diagnosis are key strategies for the effective
      control of diabetes. The main reason why a faster glycemic control should be
      implemented in an effective and safe way is to boost the confidence and the
      compliance of the patient to the recommendations of the diabetes care team.
      Better and faster results in glycemic control can only be safely achieved with
      educational strategies, structured self-monitoring of blood glucose, and adequate
      pharmacological therapy in the majority of cases.

PMID- 24892461
TI  - Santa Clara Strength of Religious Faith Questionnaire: psychometric analysis in
      older adults.
AB  - OBJECTIVES: To assist researchers and clinicians considering using the Santa
      Clara Strength of Religious Faith Questionnaire (SCSRFQ) with older-adult
      samples, the current study analyzed the psychometrics of SCSRFQ scores in two
      older-adult samples. METHOD: Adults of age 55 or older who had formerly
      participated in studies of cognitive-behavioral therapy for anxiety and/or
      depression were recruited to complete questionnaires. In Study 1 (N = 66), the
      authors assessed the relations between the SCSRFQ and other measures of
      religiousness/spirituality, mental health, and demographic variables, using
      bivariate correlations and nonparametric tests. In Study 2 (N = 223), the authors
      also conducted confirmatory and exploratory factor analyses of the SCSRFQ, as
      well as an item response theory analysis. RESULTS: The SCSRFQ was moderately to
      highly positively correlated with all measures of religiousness/spirituality.
      Relations with mental health were weak and differed across samples. Ethnic
      minorities scored higher than White participants on the SCSRFQ, but only in Study
      2. Factor analyses showed that a single-factor model fit the SCSRFQ best.
      According to item response theory analysis, SCSRFQ items discriminated well
      between participants with low-to-moderate levels of the construct but provided
      little information at higher levels. CONCLUSION: Although the SCSRFQ scores had
      adequate psychometric characteristics, the measure's usefulness may be limited in
      samples of older adults.

PMID- 24892464
TI  - 10-year follow-up of natural crown bonding after tooth fracture.
AB  - The aim of this article is to discuss relevant considerations about crown bonding
      and describe a clinical case in which a tooth fragment and direct composite resin
      were used to successfully restore a fractured anterior tooth. Clinical
      examinations showed good esthetics and periodontal health after 10 years of
      follow-up.

PMID- 24892465
TI  - [Statins for primary prevention: are the guidelines in need of improvement? -
      Preventive pharmacotherapy: indication has to be adapted individually].

PMID- 24892462
TI  - High-fat meals do not impair postprandial endothelial function in HIV-infected
      and uninfected men.
AB  - Prior studies have demonstrated impaired endothelium-dependent flow-mediated
      dilation (FMD) in healthy subjects following a high-fat meal. Compared to
      uninfected individuals, HIV-infected persons have been shown to have impaired
      FMD. We examined the effect of two different high-fat meals on endothelial
      function in HIV-infected and uninfected men. We performed a randomized, parallel
      group crossover study comparing 47 white men [18 HIV-uninfected, 9 HIV-infected
      and antiretroviral therapy (ART)-naive, and 20 HIV-infected men on ART]. Fasting
      participants consumed one of two randomly assigned high-fat meals of either
      saturated or polyunsaturated fat, followed at least 24 h later by the other meal.
      Brachial artery ultrasound measurements to assess vascular reactivity were
      performed before and 3 h after each dietary challenge. There was no significant
      difference in mean baseline or postprandial FMD between HIV-infected and HIV
      uninfected participants (mean baseline FMD+/-SD, 9.0%+/-5 vs. 9.2%+/-5, p=0.9;
      mean postprandial FMD+/-SD, 9.0%+/-4.7 vs. 9.1%+/-4.7, p=0.96, respectively). No
      significant difference in baseline or postprandial change in FMD was found
      between meals or HIV treatment groups. Fasting lipids and glucose, CD4(+) count,
      and viral load did not predict FMD in HIV-infected participants. In contrast to
      previous reports, this study did not demonstrate impaired endothelium-dependent
      vasodilation after high-fat meals in either HIV-infected or HIV-uninfected men.
      Moreover, HIV infection itself may not be the primary explanation for the
      abnormal endothelial function reported in HIV-infected individuals.

PMID- 24892466
TI  - [A very rare cause of haemoptysis - coexistence of primary oncocytic adenoma of
      trachea with bronchial carcinoma].
AB  - HISTORY AND ADMISSION FINDINGS: A 70-year-old man with a past history of COPD
      stage GOLD D with home oxygen therapy and tracheotomy due to long-term
      ventilation (898 hours) 6 years ago was admitted for investigation of haemoptysis
      during oral anticoagulation. He suffered from peripheral arterial disease (PAD)
      with bypass and repeated thrombectomy due to recurrent bypass caps, despite
      effective warfarin therapy. He had all cardiovascular risk factors.
      INVESTIGATIONS: The suspicion of a bronchial carcinoma was confirmed by CT.
      Bronchoscopically a 2 cm lesion in the left upper lobe was biopsied.
      Additionally, bronchoscopy revealed an approximately erythematous, bloody
      discolored lesion (diameter 7 mm) at a tracheotomy scar. DIAGNOSIS, TREATMENT AND
      COURSE: The biopsies revealed an adenocarcinoma in the left upper lobe and an
      oncocytic adenoma of the trachea - an extremely rare adenoma. The staging result
      was cT1b cN0 cM0 G2 IASLC Ia. Because of his severe multiple diseases the patient
      was in an inoperable condition. An interdisciplinary tumor conference recommended
      an individualized approach with a definitive radiotherapy of the adenocarcinoma.
      Endoscopic control of the macroscopically completely removed oncocytic adenoma of
      the trachea shall be performed one year later. CONCLUSIONS: Oncocytoma is an
      extremely rare adenoma (of the trachea), which in this case, has caused
      haemoptysis in addition to lung cancer during anticoagulation. For tumor genesis
      a reactive or hyperplasic response after tracheotomy 6 years ago is considered.
      Resection is the treatment of choice because of the potential for infiltrative
      growth. But the decision to treat always depends on individual benefit.

PMID- 24892467
TI  - [23-year-old bodybuilder with new skin alterations].

PMID- 24892468
TI  - [Bridging: Perioperative management of chronic anticoagulation or antiplatelet
      therapy].
AB  - Oral anticoagulants [Vitamin-K-Antagonists, Dabigatran, Rivaroxaban, Apixaban] or
      antiplatelet agents [Aspirin, Clopidogrel, Prasugrel, Ticagrelor] are effective
      in preventing thromboembolic diseases. In case of interventional of surgical
      procedures patients with indications for chronic anticoagulation [atrial
      fibrillation, valve prosthesis, venous thromboembolism] or use of antiplatelet
      agents [cerebrovascular events, cardiovascular events] will require interruption
      of antithrombotic/antiplatelet therapy with the need of replacement with a short
      acting agent. Due to limited data available from randomized studies and meta
      analyses the evidence level is low in the majority of recommendations. Therefore
      for each patient the bleeding and thrombosis risk depending on the individual
      patient constitution and the planned intervention must be weighted. In patients
      with an intermediate risk for thrombosis the bleeding risk of the scheduled
      intervention will influence the bridging recommendation: In patients with a low
      bleeding risk oral anticoagulation/antiplatelet therapy can be continued or
      reduced in intensity. In patients with an intermediate or high bleeding risk
      along with a low thrombosis risk a temporary interruption of the
      anticoagulation/antiplatelet therapy is feasible. In patients with a high
      thrombosis and bleeding risk anticoagulation should be bridged with
      unfractionated heparin [renal insufficiency] or low molecular weight heparin. In
      the latter risk situation, inhibition of platelet function can be achieved with
      short-lasting GPIIb-IIIa inhibitors [Eptifibatide, Tirofiban]. Prior to
      intervention patients treated with the new oral anticoagulants [Dabigatran;
      Rivaroxaban; Apixaban] are requested to temporary interrupt the anticoagulation
      depending on the individual drug half-life and their renal function. Bridging
      therapy with heparin prior to intervention is not necessary with the new oral
      anticoagulants. 

PMID- 24892469
TI  - [Pump system for peritoneal-vesical ascitesdrainage: principle, implantation and
      studies].

PMID- 24892470
TI  - [Malabsorption of fermentable oligo-, di-, or monosaccharides and polyols
      (FODMAP) as a common cause of unclear abdominal discomfort].
AB  - Carbohydrate malabsorption is a frequent but underestimated cause of unexplained
      gastrointestinal symptoms like meteorism, flatulence, pain and diarrhea. By means
      of hydrogen and/or methane breath test after ingestion of the respective
      carbohydrate it can be identified and diagnosed easily, fast and reliably by
      successful nutritional therapy. Besides the well known complaints caused by
      lactose and fructose malabsorption, other fermentable oligo-, di-, or
      monosaccharides and polyols (akronym: FODMAP) can cause abdominal discomfort and
      IBS-like symptoms. In addition to lactose (dairy products) and fructose (apples,
      pears, mango, watermelon), FODMAPs comprise galactans (legumes), fructans (wheat,
      onions, garlic, artichoke) and the artificial sweeteners sorbitol, mannitol,
      maltitol and xylitol (sugar free candy, light products). A general restriction of
      all FODMAP components can be beneficial in relieving symptoms and improving
      quality of life in patients with functional gastrointestinal complaints. 

PMID- 24892471
TI  - [Stress: psychosocial work load and risks for cardiovascular disease and
      depression].

PMID- 24892472
TI  - [Circadian clocks and energy metabolism].

PMID- 24892473
TI  - [Circadian clocks and energy metabolism].

PMID- 24892474
TI  - [Memories of Erwin Balz (1849-1913)].

PMID- 24892475
TI  - Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides
      leaves in rats.
AB  - The present study aimed to evaluate the toxicity of aqueous extract of
      Chenopodium ambrosioides leaves. To measure acute toxicity, rats were
      administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides
      leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral
      gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C.
      ambrosioides leaves. No animals from either trial exhibited any signs of
      toxicity. In the acute study, the highest dose of the extract led to an increase
      in the serum activities of alanine transaminase (ALT) and aspartate transaminase
      (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats
      treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and
      creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results
      indicate that aqueous extract from C. ambrosioides leaves produce slight
      hepatotoxic lesions in rats.

PMID- 24892476
TI  - Know your audience: one hospital's approach to quality improvement initiatives.

PMID- 24892477
TI  - Intravenous Abuse of Tropicamide in Opioid Use Disorder: Presentation of 2 Cases.
AB  - BACKGROUND: Tropicamide is an antimuscarinic ophthalmic solution used to produce
      short-acting mydriasis and cycloplegia. Topical abuse of ophthalmic solutions has
      been reported, but intravenous (IV) abuse of tropicamide seems to be a new
      phenomenon. CASES: The authors present 2 patients with concomitant IV tropicamide
      abuse and opioid use disorder. Patients were hospitalized and started on
      buprenorphine/naloxone treatment for opioid withdrawal. Patients' reports about
      tropicamide effects are remarkable, as they claimed that tropicamide increased
      the efficacy of heroin while decreasing and delaying the withdrawal symptoms.
      DISCUSSION: Although anticholinergics have been known to be abused for their
      euphoric effects, these cases' motivation to use tropicamide seemed to extend
      beyond its euphoric effect and was also based on its interaction with heroin. It
      is feared that tropicamide abuse may become more frequent. Health professionals
      should be aware of this trend so that symptoms of misuse and intoxication can be
      recognized, and ophthalmologists should consider the abuse potential of
      anticholinergic eye drops when prescribing them.

PMID- 24892480
TI  - Transfusion practices in evolution, not revolution*.

PMID- 24892479
TI  - Plasma exchange, methylprednisolone, IV immune globulin, and now anakinra support
      continued PICU equipoise in management of hyperferritinemia-associated
      sepsis/multiple organ dysfunction syndrome/macrophage activation
      syndrome/secondary hemophagocytic lymphohistiocytosis syndrome*.

PMID- 24892478
TI  - Conversion of partially reprogrammed cells to fully pluripotent stem cells is
      associated with further activation of stem cell maintenance- and gamete
      generation-related genes.
AB  - Somatic cells are reprogrammed to induced pluripotent stem cells (iPSCs) by
      overexpression of a combination of defined transcription factors. We generated
      iPSCs from mouse embryonic fibroblasts (with Oct4-GFP reporter) by transfection
      of pCX-OSK-2A (Oct4, Sox2, and Klf4) and pCX-cMyc vectors. We could generate
      partially reprogrammed cells (XiPS-7), which maintained more than 20 passages in
      a partially reprogrammed state; the cells expressed Nanog but were Oct4-GFP
      negative. When the cells were transferred to serum-free medium (with serum
      replacement and basic fibroblast growth factor), the XiPS-7 cells converted to
      Oct4-GFP-positive iPSCs (XiPS-7c, fully reprogrammed cells) with ESC-like
      properties. During the conversion of XiPS-7 to XiPS-7c, we found several clusters
      of slowly reprogrammed genes, which were activated at later stages of
      reprogramming. Our results suggest that partial reprogrammed cells can be induced
      to full reprogramming status by serum-free medium, in which stem cell maintenance
      and gamete generation-related genes were upregulated. These long-term expandable
      partially reprogrammed cells can be used to verify the mechanism of
      reprogramming. 

PMID- 24892481
TI  - Adults with congenital heart disease: not just big babies*.

PMID- 24892482
TI  - The utility of steroids in pediatric cardiac operations*.

PMID- 24892483
TI  - Hemodynamics in preterm neonates with septic shock: getting to the heart of the
      matter*.

PMID- 24892484
TI  - Remifentanil to relieve pain associated with peripherally inserted central
      catheters in preterm infants: the new way to go?*.

PMID- 24892485
TI  - Severe postoperative hyponatremia after pediatric intracranial tumor surgery--is
      this preventable?*.

PMID- 24892486
TI  - Taking aim at harm-adverse event detection in a South African PICU*.

PMID- 24892487
TI  - Toward a more perfect (European) union*.

PMID- 24892488
TI  - The importance of microalbuminuria in predicting patient outcome in a PICU.
AB  - OBJECTIVE: To evaluate the prognostic significance of microalbuminuria in
      critically ill children. DESIGN: Prospective study. SETTING: PICU of a teaching
      hospital. PATIENTS: Admitted critically ill children. INTERVENTIONS: The urine
      albumin-creatinine ratio was measured at admission and at 24 hours. Pediatric
      Risk of Mortality, Pediatric Index of Mortality II, Pediatric Logistic Organ
      Dysfunction, and Inotrope Score were calculated. MEASUREMENTS AND MAIN RESULTS:
      In total, 102 patients (median age, 19 mo) were included in the study, among whom
      were 30 mortalities. Microalbuminuria was identified in 62 patients (64%). The
      patients were classified into three groups: patients with sepsis, patients with
      noninfectious systemic inflammatory response syndrome, and patients without
      systemic inflammatory response syndrome. The highest clinical scores, albumin
      creatinine ratio levels, mortality rate, and duration of mechanical ventilation
      were found in the sepsis group, and the lowest values were seen in patients
      without systemic inflammatory response syndrome (p < 0.05). Significant
      correlations were observed between the albumin-creatinine ratio levels and the
      clinical scores (p < 0.05). The receiver operating characteristics curve analysis
      showed that the areas under the curves were 0.818 and 0.781, respectively, for
      albumin-creatinine ratio measured at admission and at 24 hours to identify PICU
      mortality. At a cutoff value of 34.2 mg/g, albumin-creatinine ratio measured at
      admission may be able to discriminate between patients a with sensitivity of
      63.3%, specificity of 93.3%, positive predictive value of 95%, and negative
      predictive value of 56%. CONCLUSIONS: Microalbuminuria is a simple, inexpensive,
      and useful tool for predicting mortality and morbidity in critically ill children
      in the PICU.

PMID- 24892490
TI  - Complete mitochondrial genome of the Red devil cichlid (Amphilophus citrinellus).
AB  - In this study, the complete mitochondrial genome sequence of Amphilophus
      citrinellus was firstly sequenced and determined. The total genome is 16,522 bp
      in length with an A + T content of 54.19%, and contained 13 protein-coding genes,
      22 tRNA genes, 2 ribosomal RNA genes and two main non-coding regions. The gene
      composition and order is similar to that of most other vertebrates, as is base
      composition and codon usage. These data will provide useful molecular information
      for phylogenetic relationships within the family Cichlidae species. 

PMID- 24892489
TI  - Complete mitochondrial genome of Hemisalanx brachyrostralis (Osteichthyes:
      Salangidae).
AB  - Hemisalanx brachyrostralis belonging to the family Salangidae is endemic to the
      Yangtze River. This species has been listed on the Chinese Red List because of
      the serious decrease in its resources. In this study, we analyzed the complete
      mtDNA (16588 bp long) of H. brachyrostralis. Overall base composition of the
      genome is 25.1% A, 25.4% T, 18.7% G, and 30.8% C. The complete mtDNA contains 13
      protein-coding genes, 22 tRNA genes, 2 rRNA genes (12S rRNA and 16S rRNA), and 1
      control region. Apart from the ND6 gene and nine tRNA genes encoded on the L
      strand, most of the genes are on the H-strand. H. brachyrostralis has the lowest
      genetic diversity among the Salangid species, so further studies on conservation
      genetics must be conducted. 

PMID- 24892491
TI  - Fast-growing field of magnetically recyclable nanocatalysts.

PMID- 24892492
TI  - Spatiotemporal pH dynamics in concentration polarization near ion-selective
      membranes.
AB  - We present a detailed analysis of the transient pH dynamics for a weak, buffered
      electrolyte subject to voltage-driven transport through an ion-selective
      membrane. We show that pH fronts emanate from the concentration polarization zone
      next to the membrane and that these propagating fronts change the pH in the
      system several units from its equilibrium value. The analysis is based on a 1D
      model using the unsteady Poisson-Nernst-Planck equations with nonequilibrium
      chemistry and without assumptions of electroneutrality or asymptotically thin
      electric double layers. Nonequilibrium chemical effects, especially for water
      splitting, are shown to be important for the dynamical and spatiotemporal
      evolution of the pH fronts. Nonetheless, the model also shows that at steady
      state the assumption of chemical equilibrium can still lead to good
      approximations of the global pH distribution. Moreover, our model shows that the
      transport of the hydronium ion in the extended space charge region is governed by
      a balance between electromigration and water self-ionization. On the basis of
      this observation, we present a simple model showing that the net flux of the
      hydronium ion is proportional to the length of the extended space charge region
      and the water self-ionization rate. To demonstrate these effects in practice, we
      have adopted the experiment of Mai et al. (Mai, J.; Miller, H.; Hatch, A. V.
      Spatiotemporal Mapping of Concentration Polarization Induced pH Changes at
      Nanoconstrictions. ACS Nano 2012, 6, 10206) as a model problem, and by including
      the full chemistry and transport, we show that the present model can capture the
      experimentally observed pH fronts. Our model can, among other things, be used to
      predict and engineer pH dynamics, which can be essential to the performance of
      membrane-based systems for biochemical separation and analysis. 

PMID- 24892494
TI  - A flexible microcontroller-based data acquisition device.
AB  - This paper presents a low-cost microcontroller-based data acquisition device. The
      key component of the presented solution is a configurable microcontroller-based
      device with an integrated USB transceiver and a 12-bit analogue-to-digital
      converter (ADC). The presented embedded DAQ device contains a preloaded program
      (firmware) that enables easy acquisition and generation of analogue and digital
      signals and data transfer between the device and the application running on a PC
      via USB bus. This device has been developed as a USB human interface device
      (HID). This USB class is natively supported by most of the operating systems and
      therefore any installation of additional USB drivers is unnecessary. The
      input/output peripheral of the presented device is not static but rather
      flexible, and could be easily configured to customised needs without changing the
      firmware. When using the developed configuration utility, a majority of chip pins
      can be configured as analogue input, digital input/output, PWM output or one of
      the SPI lines. In addition, LabVIEW drivers have been developed for this device.
      When using the developed drivers, data acquisition and signal processing
      algorithms as well as graphical user interface (GUI), can easily be developed
      using a well-known, industry proven, block oriented LabVIEW programming
      environment. 

PMID- 24892493
TI  - Electrical impedance spectroscopy for electro-mechanical characterization of
      conductive fabrics.
AB  - When we use a conductive fabric as a pressure sensor, it is necessary to
      quantitatively understand its electromechanical property related with the applied
      pressure. We investigated electromechanical properties of three different
      conductive fabrics using the electrical impedance spectroscopy (EIS). We found
      that their electrical impedance spectra depend not only on the electrical
      properties of the conductive yarns, but also on their weaving structures. When we
      apply a mechanical tension or compression, there occur structural deformations in
      the conductive fabrics altering their apparent electrical impedance spectra. For
      a stretchable conductive fabric, the impedance magnitude increased or decreased
      under tension or compression, respectively. For an almost non-stretchable
      conductive fabric, both tension and compression resulted in decreased impedance
      values since the applied tension failed to elongate the fabric. To measure both
      tension and compression separately, it is desirable to use a stretchable
      conductive fabric. For any conductive fabric chosen as a pressure-sensing
      material, its resistivity under no loading conditions must be carefully chosen
      since it determines a measurable range of the impedance values subject to
      different amounts of loadings. We suggest the EIS method to characterize the
      electromechanical property of a conductive fabric in designing a thin and
      flexible fabric pressure sensor. 

PMID- 24892495
TI  - Chemical analysis and molecular models for calcium-oxygen-carbon interactions in
      black carbon found in fertile Amazonian anthrosoils.
AB  - Carbon particles containing mineral matter promote soil fertility, helping it to
      overcome the rather unfavorable climate conditions of the humid tropics.
      Intriguing examples are the Amazonian Dark Earths, anthropogenic soils also known
      as "Terra Preta de Indio'' (TPI), in which chemical recalcitrance and stable
      carbon with millenary mean residence times have been observed. Recently, the
      presence of calcium and oxygen within TPI-carbon nanoparticles at the nano- and
      mesoscale ranges has been demonstrated. In this work, we combine density
      functional theory calculations, scanning transmission electron microscopy, energy
      dispersive X-ray spectroscopy, Fourier transformed infrared spectroscopy, and
      high resolution X-ray photoelectron spectroscopy of TPI-carbons to elucidate the
      chemical arrangements of calcium-oxygen-carbon groups at the molecular level in
      TPI. The molecular models are based on graphene oxide nanostructures in which
      calcium cations are strongly adsorbed at the oxide sites. The application of
      material science techniques to the field of soil science facilitates a new level
      of understanding, providing insights into the structure and functionality of
      recalcitrant carbon in soil and its implications for food production and climate
      change. 

PMID- 24892496
TI  - Fluorescent probe-based lateral flow assay for multiplex nucleic acid detection.
AB  - Here we report a rapid, low cost, and disposable dipstick-type DNA biosensor that
      enables multiplex detection in a single assay. The fluorescent probes labeled
      with different fluorophores were introduced into the lateral flow nucleic acid
      testing system. In combination with multiple immobilized probes arranged in an
      array formant on the membrane, a dual-color fluorescent lateral flow DNA
      biosensor was developed using a portable fluorescence reader. Up to 13 human
      papillomavirus types could be detected simultaneously by a single-step operation
      in less than 30 min after linear-after-the-exponential (LATE)-PCR. The
      sensitivity was determined to be 10-10(2) copies plasmid DNA/MUL. The specificity
      study showed no cross-reactivity among the 31 different common HPV types. In the
      clinical validation, 95.3% overall agreement showed very good potential for this
      method in the clinical application when compared to a commercial kit. 

PMID- 24892498
TI  - Cleavable PEGylation and hydrophobic histidylation of polylysine for siRNA
      delivery and tumor gene therapy.
AB  - Polylysine with cleavable PEGylation and hydrophobic histidylation (mPEG-SS-Lysn
      r-Hism) was designed and developed for efficient siRNA delivery and tumor
      therapy. mPEG-SS-Lysn-r-Hism was used to carry and deliver small interfering RNA
      (siRNA) for silencing endogenous vascular endothelial growth factor (VEGF)
      expression and inhibiting tumor growth in HepG2 tumor-bearing mice. In this gene
      vector, histidine(Bzl) was selected for hydrophobic histidylation for the proton
      sponge ability of the imidazole ring and hydrophobic benzyl group. Cleavable
      PEGylation was introduced for in vivo circulation as well as selective PEG
      detachment in response to intracellular reduction condition in order to release
      the genetic payload. PEG detachment induced gene release was supported by agarose
      gel electrophoresis retardation assay, undertaken in the intracellular relevant
      reduction condition. In vitro transfection evaluation of histidylated copolymers,
      using pEGFP as genetic model, indicated significantly higher GFP expression than
      unmodified counterparts, comparable to the gold standard PEI. The efficacy of
      hydrophobic histidylation was found to be pronounced in mesenchymal stem cells
      (MSCs). In vivo application of the VEGF-siRNA package by tailored mPEG-SS-Lysn-r
      Hism showed distinct tumor suppression in terms of macroscopic tumor volume and
      molecular analysis. 

PMID- 24892497
TI  - Optimization of SERS tag intensity, binding footprint, and emittance.
AB  - Nanoparticle surface enhanced Raman scattering (SERS) tags have attracted
      interest as labels for use in a variety of applications, including biomolecular
      assays. An obstacle to progress in this area is a lack of standardized approaches
      to compare the brightness of different SERS tags within and between laboratories.
      Here we present an approach based on binding of SERS tags to beads with known
      binding capacities that allows evaluation of the average intensity, the relative
      binding footprint of particles in a SERS tag preparation, and the size-normalized
      intensity or emittance. We tested this on four different SERS tag compositions
      and show that aggregated gold nanorods produce SERS tags that are 2-4 times
      brighter than relatively more monodisperse nanorods, but that the aggregated
      nanorods are also correspondingly larger, which may negate the intensity if
      steric hindrance limits the number of tags bound to a target. By contrast, SERS
      tags prepared from smaller gold nanorods coated with a silver shell produce SERS
      tags that are 2-3 times brighter, on a size-normalized basis, than the Au nanorod
      based tags, resulting in labels with improved performance in SERS-based image and
      flow cytometry assays. SERS tags based on red-resonant Ag plates showed similarly
      bright signals and small footprint. This approach to evaluating SERS tag
      brightness is general, uses readily available reagents and instruments, and
      should be suitable for interlab comparisons of SERS tag brightness. 

PMID- 24892500
TI  - Built to disappear.
AB  - Microelectronics dominates the technological and commercial landscape of today's
      electronics industry; ultrahigh density integrated circuits on rigid silicon
      provide the computing power for smart appliances that help us organize our daily
      lives. Integrated circuits function flawlessly for decades, yet we like to
      replace smart phones and tablet computers every year. Disposable electronics,
      built to disappear in a controlled fashion after the intended lifespan, may be
      one of the potential applications of transient single-crystalline silicon
      nanomembranes, reported by Hwang et al. in this issue of ACS Nano. We briefly
      outline the development of this latest branch of electronics research, and we
      present some prospects for future developments. Electronics is steadily evolving,
      and 20 years from now we may find it perfectly normal for smart appliances to be
      embedded everywhere, on textiles, on our skin, and even in our body. 

PMID- 24892499
TI  - Flexible high-energy Li-ion batteries with fast-charging capability.
AB  - With the development of flexible mobile devices, flexible Li-ion batteries have
      naturally received much attention. Previously, all reported flexible components
      have had shortcomings related to power and energy performance. In this research,
      in order to overcome these problems while maintaining the flexibility, honeycomb
      patterned Cu and Al materials were used as current collectors to achieve maximum
      adhesion in the electrodes. In addition, to increase the energy and power
      multishelled LiNi0.75Co0.11Mn0.14O2 particles consisting of nanoscale V2O5 and
      LixV2O5 coating layers and a LideltaNi0.75-zCo0.11Mn0.14VzO2 doping layer were
      used as the cathode-anode composite (denoted as PNG-AES) consisting of amorphous
      Si nanoparticles (<20 nm) loaded on expanded graphite (10 wt %) and natural
      graphite (85 wt %). Li-ion cells with these three elements (cathode, anode, and
      current collector) exhibited excellent power and energy performance along with
      stable cycling stability up to 200 cycles in an in situ bending test.

PMID- 24892501
TI  - Structural and medium effects on the reactions of the cumyloxyl radical with
      intramolecular hydrogen bonded phenols. The interplay between hydrogen-bonding
      and acid-base interactions on the hydrogen atom transfer reactivity and
      selectivity.
AB  - A time-resolved kinetic study on the reactions of the cumyloxyl radical (CumO(*))
      with intramolecularly hydrogen bonded 2-(1-piperidinylmethyl)phenol (1) and 4
      methoxy-2-(1-piperidinylmethyl)phenol (2) and with 4-methoxy-3-(1
      piperidinylmethyl)phenol (3) has been carried out. In acetonitrile,
      intramolecular hydrogen bonding protects the phenolic O-H of 1 and 2 from attack
      by CumO(*) and hydrogen atom transfer (HAT) exclusively occurs from the C-H bonds
      that are alpha to the piperidine nitrogen (alpha-C-H bonds). With 3 HAT from both
      the phenolic O-H and the alpha-C-H bonds is observed. In the presence of TFA or
      Mg(ClO4)2, protonation or Mg(2+) complexation of the piperidine nitrogen removes
      the intramolecular hydrogen bond in 1 and 2 and strongly deactivates the alpha-C
      H bonds of the three substrates. Under these conditions, HAT to CumO(*)
      exclusively occurs from the phenolic O-H group of 1-3. These results clearly show
      that in these systems the interplay between intramolecular hydrogen bonding and
      Bronsted and Lewis acid-base interactions can drastically influence both the HAT
      reactivity and selectivity. The possible implications of these findings are
      discussed in the framework of the important role played by tyrosyl radicals in
      biological systems. 

PMID- 24892502
TI  - The role and importance of glycosylation of acute phase proteins with focus on
      alpha-1 antitrypsin in acute and chronic inflammatory conditions.
AB  - Acute phase proteins (APPs) are a group of circulating plasma proteins which
      undergo changes quantitatively or qualitatively at the time of inflammation. Many
      of these APPs are glycosylated, and it has been shown that alterations in
      glycosylation may occur in inflammatory and malignant conditions. Changes in
      glycosylation have been studied as potential biomarkers in cancer and also in
      chronic inflammatory conditions and have been shown to correlate with disease
      severity in certain conditions. Serine protease inhibitors (serpins), many of
      which are also APPs, are proteins involved in the control of proteases in
      numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within
      the circulation and is an APP which has been shown to increase in response to
      inflammation. The primary role of AAT is maintaining the protease/antiprotease
      balance in the lung, but it also possesses important anti-inflammatory and immune
      modulating properties. Several glycoforms of AAT exist, and they possess
      differing properties in regard to plasma half-life and stability. Glycosylation
      may also be important in determining the immune modulatory properties of AAT. The
      review will focus on the role and importance of glycosylation in acute phase
      proteins with particular attention to AAT and its use as a biomarker of disease.
      The review describes the processes involved in glycosylation, how glycosylation
      changes in differing disease states, and the alterations that occur to glycans of
      APPs with disease and inflammation. Finally, the review explores the importance
      of changes in glycosylation of AAT at times of inflammation and in malignant
      conditions and how this may impact upon the functions of AAT. 

PMID- 24892503
TI  - Enhancing intermediate state absorption of resonance-mediated multiphoton
      absorption process.
AB  - We theoretically and experimentally demonstrate the control of the intermediate
      state absorption in (1+2) resonance-mediated multiphoton absorption process by
      shaping the femosecond laser pulse. A theoretical model is proposed to
      investigate the intermediate state absorption of (1+2) resonance-mediated three
      photon absorption process in the molecular system, and an analytical solution is
      obtained on the basis of time-dependent perturbation theory. Our theoretical
      results show that the intermediate state absorption can be enhanced by
      controlling the laser spectral phase due to final state absorption reduction, and
      this absorption enhancement efficiency increases with the increase of the laser
      intensity. These theoretical results are experimentally confirmed in IR144 dye by
      varying the laser spectral phase with a sinusoidal modulation function. 

PMID- 24892504
TI  - Discovery of X-ray pulsations from a massive star.
AB  - X-ray emission from stars much more massive than the Sun was discovered only 35
      years ago. Such stars drive fast stellar winds where shocks can develop, and it
      is commonly assumed that the X-rays emerge from the shock-heated plasma. Many
      massive stars additionally pulsate. However, hitherto it was neither
      theoretically predicted nor observed that these pulsations would affect their X
      ray emission. All X-ray pulsars known so far are associated with degenerate
      objects, either neutron stars or white dwarfs. Here we report the discovery of
      pulsating X-rays from a non-degenerate object, the massive B-type star xi(1) CMa.
      This star is a variable of beta Cep-type and has a strong magnetic field. Our
      observations with the X-ray Multi-Mirror (XMM-Newton) telescope reveal X-ray
      pulsations with the same period as the fundamental stellar oscillations. This
      discovery challenges our understanding of stellar winds from massive stars, their
      X-ray emission and their magnetism. 

PMID- 24892505
TI  - Reduced antibiotic use in livestock: how Denmark tackled resistance.

PMID- 24892506
TI  - General practitioners' beliefs about the clinical utility of complementary and
      alternative medicine.
AB  - AIM: To investigate GPs' beliefs about complementary and alternative medicine
      (CAM) and its role in clinical practice. BACKGROUND: Despite the prevalence of
      CAM in the United Kingdom, little is known about GPs beliefs regarding these
      alternative approaches to patient management and how they view it in relation to
      their clinical conduct and practice. METHOD: A qualitative study conducted on 19
      GPs recruited from the North West of England. Semi-structured telephone
      interviews were analysed using an inductive thematic analysis. RESULTS: Three
      themes emerged from the data: limited evidence base, patient demand and concerns
      over regulation. CONCLUSION: Despite recognising the limited evidence base of
      CAM, GPs continue to see a role for it within clinical practice. This is not
      necessarily led by patient demand that is highly related to affluence. However,
      GPs raised concerns over the regulation of CAM practitioners and CAM therapies.

PMID- 24892507
TI  - Detection of early glaucomatous progression with octopus cluster trend analysis.
AB  - PURPOSE: To compare the ability of Corrected Cluster Trend Analysis (CCTA) and
      Cluster Trend Analysis (CTA) with event analysis of Octopus visual field series
      to detect early glaucomatous progression. METHODS: One eye of 15 healthy, 19
      ocular hypertensive, 20 preperimetric, and 51 perimetric glaucoma (PG) patients
      were investigated with Octopus normal G2 test at 6-month intervals for 1.5 to 3
      years. Progression was defined with significant worsening in any of the 10
      Octopus clusters with CCTA, and event analysis criteria, respectively. RESULTS:
      With event analysis, 9 PG eyes showed localized progression and 1 diffuse mean
      defect (MD) worsening. With CCTA, progression was indicated in 1 normal, 1 ocular
      hypertensive, and 1 preperimetric glaucoma eyes due to vitreous floaters, and 28
      PG eyes including all 9 eyes with localized progression with event analysis. The
      locations of CCTA progression matched those found with event analysis in all 9
      cases. In 17 of the remaining 19 eyes, progressing clusters matched the locations
      that were suspicious but not definitive for progression with event analysis. In
      the eye with diffuse MD worsening, CTA found significant progression for 7
      clusters. For global MD progression rate, eyes worsened with CCTA only did not
      differ from the stable eyes but had significantly smaller progression rates than
      the eyes progressed with event analysis (P=0.0002). CONCLUSIONS: In PG, Octopus
      CCTA and CTA are clinically useful to identify early progression and areas
      suspicious for early progression. However, in some eyes with no glaucomatous
      visual field damage, vitreous floaters may cause progression artifacts.

PMID- 24892509
TI  - Identification of skin lesions through aminolaevulinic acid-mediated photodynamic
      detection.
AB  - Non-melanoma skin cancer is the most common cancer lesion worldwide. In Brazil,
      it represents 95% of all skin cancer lesions, and 25% of all tumor types. Early
      diagnosis allows treatment at initial stages of the disease, improving patient's
      prognosis. Thus, it is of great importance the development of techniques to aid
      diagnosis, such as marked fluorescence, which we propose here for early detection
      of skin cancer lesions. In this study, we use a photosensitive substance,
      aminolaevulinic acid (ALA), as biomarkers, and analyze its in situ fluorescence
      response to light excitation. The use of ALA as a biomarker precursor is
      interesting because it shows selectivity for protoporphyrin IX
      production/concentration in abnormal cells. Protoporphyrin IX shows high
      fluorescence yield when excited with UV-blue light. In this study, ALA solutions
      (at 5% and 10% concentrations) were applied to malignant (basal cell carcinoma)
      and potentially malignant skin lesions (actinic and seborrheic keratoses), aiming
      to investigate our ability in detecting and distinguishing them by using this
      technique. At regular time intervals (15, 30, 45 and 60min), fluorescence images
      were collected with a prototype system for widefield fluorescence imaging. ALA
      has provided a marked fluorescence that allowed significant discrimination of
      normal and tumor. Potentially malignant and benign lesions were all well
      identified by their autofluorescence; photodynamic detection did not improve
      diagnostics. This technique also provided a better delineation of the lesion
      margins, which is very important for an effective treatment of malignant,
      potentially malignant and benign skin lesions. 

PMID- 24892508
TI  - Simultaneous analysis of skin penetration of surfactant and active drug from
      fluorosurfactant-based microemulsions.
AB  - The purpose of this study was to investigate the penetrated amount of the
      incorporated model drug diclofenac-sodium and of a fluorosurfactant as specific
      vehicle constituent of topically applied microemulsions at the same time. To this
      end, the penetration depth of each compound was elucidated through tape stripping
      studies by the simultaneous quantification of diclofenac-sodium and the
      fluorosurfactant from the same sample. A new approach was made by using the very
      sensitive and specific (19)F NMR (nuclear magnetic resonance) for quantification
      of the fluorinated vehicle component. The tape stripping experiments with the
      microemulsions showed an almost similar penetration velocity of diclofenac-sodium
      and fluorosurfactant, suggesting that the surfactant within the microemulsion
      structure intensified the stratum corneum uptake of the incorporated active
      constituent. Moreover, ATR-FTIR studies on porcine ear skin revealed significant
      shifts of the CH2 stretching absorbances, which are associated with an enhanced
      disorder of the SC lipids resulting in a decreased skin barrier function, after
      application of the microemulsions. However, the application of pure
      fluorosurfactant did not cause any shifts in the CH2 stretching absorbances. It
      can be thereby concluded that the prepared microemulsions exerted specific
      effects on skin integrity resulting in a "push" of diclofenac-sodium penetration.

PMID- 24892512
TI  - An improved and versatile methodology to quantify biofilms formed on solid
      surfaces and exposed to the air-liquid interphase.
AB  - To study pellicle formation, a new method has been developed to quantify biofilm
      formed on solid surfaces and exposed to air-liquid interphase. It is a versatile
      system since different adherent material surfaces might be tested. The
      methodology is a robust and reproducible approach to quantify biofilm. 

PMID- 24892511
TI  - Statin underuse and low prevalence of LDL-C control among U.S. adults at high
      risk of coronary heart disease.
AB  - BACKGROUND: Statins reduce the risk of coronary heart disease (CHD) in
      individuals with a history of CHD or risk equivalents. A 10-year CHD risk >20% is
      considered a risk equivalent but is frequently not detected. Statin use and low
      density lipoprotein cholesterol (LDL-C) control were examined among participants
      with CHD or risk equivalents in the nationwide Reasons for Geographic and Racial
      Differences in Stroke study (n = 8812). METHODS: Participants were categorized
      into 4 mutually exclusive groups: (1) history of CHD (n = 4025); (2) no history
      of CHD but with a history of stroke and/or abdominal aortic aneurysm (AAA) (n =
      946); (3) no history of CHD or stroke/AAA but with diabetes mellitus (n = 3134);
      or (4) no history of the conditions in (1) through (3) but with 10-year
      Framingham CHD risk score (FRS) >20% calculated using the third Adult Treatment
      Panel point scoring system (n = 707). RESULTS: Statins were used by 58.4% of
      those in the CHD group and 41.7%, 40.4% and 20.1% of those in the stroke/AAA,
      diabetes mellitus and FRS >20% groups, respectively. Among those taking statins,
      65.1% had LDL-C <100 mg/dL, with no difference between the CHD, stroke/AAA, or
      diabetes mellitus groups. However, compared with those in the CHD group, LDL-C
      <100 mg/dL was less common among participants in the FRS >20% group
      (multivariable adjusted prevalence ratio: 0.72; 95% confidence interval: 0.62
      0.85). Results were similar using the 2013 American College of
      Cardiology/American Heart Association cholesterol treatment guideline.
      CONCLUSIONS: These data suggest that many people with high CHD risk, especially
      those with an FRS >20%, do not receive guideline-concordant lipid-lowering
      therapy and do not achieve an LDL-C <100 mg/dL.

PMID- 24892513
TI  - A critical combination of operating parameters can significantly increase the
      electrotransformation efficiency of a gram-positive Dietzia strain.
AB  - Dietzia spp. have broad potential applications in industries. However, genetic
      manipulation of these species is obstructed by their low transformation
      efficiency, which is in the range of 10(4)colony-forming units (CFU)MUg(-1)
      exogenous DNA. In this study, both single-factor and orthogonal experiments were
      conducted to test the effects of competent cell concentration (parameter A),
      electroporation time (B), and field strength (C), as well as the concentrations
      of glycine (D), isonicotinic acid hydrazide (INH, E), Tween 80 (F), and
      penicillin G (G) on the electrotransformation efficiency of Dietzia sp. DQ12-45
      1b. The order in which the parameters contributed to electrotransformation
      efficiency was C>D>F>G>B>A>E, suggesting that field strength, glycine, and Tween
      80 each had a greater capability to increase electrotransformation efficiency
      than the other parameters tested. Using the optimized protocol deduced from the
      results of the orthogonal experiments, the electrotransformation efficiency of
      Dietzia sp. DQ12-45-1b reached 2.51*10(7)CFUMUg(-1) plasmid. To the best of our
      knowledge, this is the highest transformation efficiency that has been reported
      for Dietzia bacteria to date. Thus, we present a method that combines the
      transformation factors to obtain the optimal transformation efficiency for a
      target bacterium. 

PMID- 24892514
TI  - Silver(I)/6-hydroxyiminolumazine compounds differently modify renin-angiotensin
      system-regulating aminopeptidases A and N in human neuroblastoma and glioma
      cells.
AB  - We have described that local tissue renin-angiotensin-system (RAS) is involved in
      tumor growth in a rat model of experimental glioma in vivo, through the
      modification of their corresponding local proteolytic regulatory enzymes. Thus,
      we have found a time-dependent significant decrease in aminopeptidase N (APN) and
      a significant increase in aminopeptidase A (APA) activities concomitantly with
      tumor growth in tumor tissue whereas no changes were found in circulating
      aminopeptidase activities; we suggested that angiotensin peptides may play an
      essential step in both tumor infiltration and associated angiogenesis. Here we
      analyze in vitro the antiproliferative efficacy, apoptotic properties and effects
      of three new disilver complexes containing E-6-(hydroxyimino)ethyl-1,3,7
      trimethyllumazine (lumazine=pteridine-2,4(1H,3H)-dione) on RAS-regulating APA and
      APN specific activities in human neuroblastoma and glioma cell lines NB69 and
      U373-MG. Disilver compounds showed cytotoxicity against both cell lines, although
      their potency was different for each cell type. Furthermore, NB69 cells need
      higher concentrations of silver complexes than U373-MG cells to obtain a 50%
      growth inhibition. All compounds showed apoptotic effects, with U373-MG cells
      being more susceptible. The three silver complexes tested also show a dose
      dependent inhibitory effect on APA activity in NB69 and U373-MG cells, although
      U373-MG cells are more sensitive. On the contrary, none of them showed effects on
      APN activity in NB69 neuroblastoma cells whereas the three compounds showed a
      dose-dependent stimulatory effect on APN activity in U373-MG glioma cells with a
      similar potency. Disilver complexes show specific antitumor activity against
      brain tumor cells acting through the paracrine regulating system mediated by
      local tissue RAS. 

PMID- 24892515
TI  - Outcomes of endoscopic human thrombin injection in the management of gastric
      varices.
AB  - OBJECTIVE: Endoscopic human thrombin injection appears to be a technically simple
      and efficacious alternative to tissue adhesives with fewer complications;
      however, data remain limited. We analysed our experience using endoscopic human
      thrombin injection for gastric varices in a tertiary referral liver unit.
      METHODS: Thirty patients received thrombin injection for gastric varices between
      December 2008 and January 2013. Twenty patients (67%) had active bleeding or
      signs of recent bleeding at endoscopy. Ten patients (33%) received thrombin for
      prophylaxis of rebleeding: secondary (eight patients) and primary (two patients).
      RESULTS: The mean thrombin dose/injection was 1100 IU (range 400-2500); the mean
      number of sessions was two (range 1-9), with no reported complications.
      Haemostasis was achieved in 18 out of 20 (90%) patients treated acutely. Failure
      to control bleeding (bleeding before day 5) was seen in seven patients: three
      died and four were managed successfully [two with further thrombin and two using
      a salvage transjugular intrahepatic portosystemic shunt (TIPSS)]. Rebleeding
      occurred in a further four patients, all managed successfully with salvage TIPSS.
      In the prophylaxis group, rebleeding occurred in two out of 10 patients.The
      median follow-up period was 672 days (interquartile range 92-1331). One patient
      underwent liver transplantation. Ten deaths occurred in total: four due to
      gastric variceal bleeding. Six-week survival was 83%. In cases in which TIPSS was
      precluded, 91% of patients (10 out of 11 patients) were managed successfully with
      thrombin. CONCLUSION: Endoscopic thrombin therapy for gastric variceal bleeding
      may have most utility as a safe and easily applied bridge to more definitive
      therapy, in secondary prophylaxis of rebleeding and in cases in which TIPSS is
      precluded.

PMID- 24892516
TI  - Practical treatment of Helicobacter pylori: a balanced view in changing times.
AB  - Eradication rates of first-line triple therapy for Helicobacter pylori infection
      have fallen in the recent years. The main reasons for treatment failure are poor
      compliance due to complicated treatment regimens and the emergence of antibiotic
      resistant strains of H. pylori. Treatment failure is a cause for concern with
      regard to the complications of H. pylori infection, which include gastric and
      peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma.
      This review describes considerations for optimizing standard first-line triple
      therapy, as well as alternatives to the standard first-line treatment, such as
      bismuth quadruple therapy, sequential therapy, concomitant therapy and hybrid
      therapy. Studies using levofloxacin-based and rifabutin-based regimens for the
      treatment of multiresistant infections have also been reviewed. The current most
      up-to-date systematic reviews and meta-analyses comparing the efficacy of these
      treatments have been discussed, in light of the recent antimicrobial
      susceptibility testing data, regional antibiotic resistance rates and the
      Maastricht IV guidelines on the management of H. pylori infection. 

PMID- 24892517
TI  - Chlorambucil (nitrogen mustard) induced impairment of early vascular endothelial
      cell migration - effects of alpha-linolenic acid and N-acetylcysteine.
AB  - Alkylating agents (e.g. sulfur and nitrogen mustards) cause a variety of cell and
      tissue damage including wound healing disorder. Migration of endothelial cells is
      of utmost importance for effective wound healing. In this study we investigated
      the effects of chlorambucil (a nitrogen mustard) on early endothelial cells (EEC)
      with special focus on cell migration. Chlorambucil significantly inhibited
      migration of EEC in Boyden chamber and wound healing experiments. Cell migration
      is linked to cytoskeletal organization. We therefore investigated the
      distribution pattern of the Golgi apparatus as a marker of cell polarity. Cells
      are polarized under control conditions, whereas chlorambucil caused an encircling
      perinuclear position of the Golgi apparatus, indicating non-polarized cells. ROS
      are discussed to be involved in the pathophysiology of alkylating substances and
      are linked to cell migration and cell polarity. Therefore we investigated the
      influence of ROS-scavengers (alpha-linolenic acid (ALA) and N-acetylcysteine
      (NAC)) on the impaired EEC migration. Both substances, in particular ALA,
      improved EEC migration. Notably ALA restored cell polarity. Remarkably,
      investigations of ROS and RNS biomarkers (8-isoprostane and nitrotyrosine) did
      not reveal a significant increase after chlorambucil exposure when assessed 24h
      post exposure. A distinct breakdown of mitochondrial membrane potential (measured
      by TMRM) that recovered under ALA treatment was observed. In conclusion our
      results provide compelling evidence that the alkylating agent chlorambucil
      dramatically impairs directed cellular migration, which is accompanied by
      perturbations of cell polarity and mitochondrial membrane potential. ALA
      treatment was able to reconstitute cell polarity and to stabilize mitochondrial
      potential resulting in improved cell migration. 

PMID- 24892519
TI  - Caffeine and cognitive performance: persistent methodological challenges in
      caffeine research.
AB  - Human cognitive performance is widely perceived to be enhanced by caffeine at
      usual dietary doses. However, the evidence for and against this belief continues
      to be vigorously contested. Controversy has centred on caffeine withdrawal and
      withdrawal reversal as potential sources of experimental confounding. In
      response, some researchers have enlisted "caffeine-naive" experimental
      participants (persons alleged to consume little or no caffeine) assuming that
      they are not subject to withdrawal. This mini-review examines relevant research
      to illustrate general methodological challenges that have been the cause of
      enduring confusion in caffeine research. At issue are the processes of caffeine
      withdrawal and withdrawal reversal, the definition of caffeine-naive, the
      population representativeness of participants deemed to be caffeine-naive, and
      confounding due to caffeine tolerance. Attention to these processes is necessary
      if premature conclusions are to be avoided, and if caffeine's complex effects and
      the mechanisms responsible for those effects are to be illuminated. Strategies
      are described for future caffeine research aimed at minimising confounding from
      withdrawal and withdrawal reversal. 

PMID- 24892518
TI  - A mechanistic study on the anti-cancer activity of ethyl caffeate in human
      ovarian cancer SKOV-3 cells.
AB  - In the present study, we investigated the effect and molecular mechanism of ethyl
      caffeate (EC), a natural phenolic compound isolated from Ligularia fischeri, on
      human ovarian cancer cell proliferation and progression. EC-mediated inhibition
      of cell proliferation in SKOV-3 cells was accompanied by reduced expression of
      cell cycle-related proteins such as cyclin-dependent kinases and cyclins,
      resulting in pRb hypophosphorylation and G1 phase cell cycle arrest. Moreover, EC
      treatment markedly inhibited cell migration and invasion. These regulatory
      effects of EC on ovarian cancer cell proliferation, migration and invasion were
      associated with inactivation of mitogenic signaling pathways such as Akt, ERK and
      p38(MAPK), and down-regulation of cell surface signaling molecules including
      receptor tyrosine kinases, integrin alpha3beta1 and N-cadherin. Taken together,
      these findings suggest further evaluation and development of EC for the treatment
      and prevention of ovarian cancer.

PMID- 24892520
TI  - Estimating landholders' probability of participating in a stewardship program,
      and the implications for spatial conservation priorities.
AB  - The need to integrate social and economic factors into conservation planning has
      become a focus of academic discussions and has important practical implications
      for the implementation of conservation areas, both private and public. We
      conducted a survey in the Daly Catchment, Northern Territory, to inform the
      design and implementation of a stewardship payment program. We used a choice
      model to estimate the likely level of participation in two legal arrangements-
      conservation covenants and management agreements--based on payment level and
      proportion of properties required to be managed. We then spatially predicted
      landholders' probability of participating at the resolution of individual
      properties and incorporated these predictions into conservation planning software
      to examine the potential for the stewardship program to meet conservation
      objectives. We found that the properties that were least costly, per unit area,
      to manage were also the least likely to participate. This highlights a tension
      between planning for a cost-effective program and planning for a program that
      targets properties with the highest probability of participation.

PMID- 24892522
TI  - Enhanced photoacoustic gas analyser response time and impact on accuracy at fast
      ventilation rates during multiple breath washout.
AB  - BACKGROUND: The Innocor device contains a highly sensitive photoacoustic gas
      analyser that has been used to perform multiple breath washout (MBW) measurements
      using very low concentrations of the tracer gas SF6. Use in smaller subjects has
      been restricted by the requirement for a gas analyser response time of <100 ms,
      in order to ensure accurate estimation of lung volumes at rapid ventilation
      rates. METHODS: A series of previously reported and novel enhancements were made
      to the gas analyser to produce a clinically practical system with a reduced
      response time. An enhanced lung model system, capable of delivering highly
      accurate ventilation rates and volumes, was used to assess in vitro accuracy of
      functional residual capacity (FRC) volume calculation and the effects of flow and
      gas signal alignment on this. RESULTS: 10-90% rise time was reduced from 154 to
      88 ms. In an adult/child lung model, accuracy of volume calculation was -0.9 to
      2.9% for all measurements, including those with ventilation rate of 30/min and
      FRC of 0.5 L; for the un-enhanced system, accuracy deteriorated at higher
      ventilation rates and smaller FRC. In a separate smaller lung model (ventilation
      rate 60/min, FRC 250 ml, tidal volume 100 ml), mean accuracy of FRC measurement
      for the enhanced system was minus 0.95% (range -3.8 to 2.0%). Error sensitivity
      to flow and gas signal alignment was increased by ventilation rate, smaller FRC
      and slower analyser response time. CONCLUSION: The Innocor analyser can be
      enhanced to reliably generate highly accurate FRC measurements down at volumes as
      low as those simulating infant lung settings. Signal alignment is a critical
      factor. With these enhancements, the Innocor analyser exceeds key technical
      component recommendations for MBW apparatus.

PMID- 24892523
TI  - Overexpression of phosphomimic mutated OsWRKY53 leads to enhanced blast
      resistance in rice.
AB  - WRKY transcription factors and mitogen-activated protein kinase (MAPK) cascades
      have been shown to play pivotal roles in the regulation of plant defense
      responses. We previously reported that OsWRKY53-overexpressing rice plants showed
      enhanced resistance to the rice blast fungus. In this study, we identified
      OsWRKY53 as a substrate of OsMPK3/OsMPK6, components of a fungal PAMP-responsive
      MAPK cascade in rice, and analyzed the effect of OsWRKY53 phosphorylation on the
      regulation of basal defense responses to a virulence race of rice blast fungus
      Magnaporthe oryzae strain Ina86-137. An in vitro phosphorylation assay revealed
      that the OsMPK3/OsMPK6 activated by OsMKK4 phosphorylated OsWRKY53 recombinant
      protein at its multiple clustered serine-proline residues (SP cluster). When
      OsWRKY53 was coexpressed with a constitutively active mutant of OsMKK4 in a
      transient reporter gene assay, the enhanced transactivation activity of OsWRKY53
      was found to be dependent on phosphorylation of the SP cluster. Transgenic rice
      plants overexpressing a phospho-mimic mutant of OsWRKY53 (OsWRKY53SD) showed
      further-enhanced disease resistance to the blast fungus compared to native
      OsWRKY53-overexpressing rice plants, and a substantial number of defense-related
      genes, including pathogenesis-related protein genes, were more upregulated in the
      OsWRKY53SD-overexpressing plants compared to the OsWRKY53-overexpressing plants.
      These results strongly suggest that the OsMKK4-OsMPK3/OsMPK6 cascade regulates
      transactivation activity of OsWRKY53, and overexpression of the phospho-mimic
      mutant of OsWRKY53 results in a major change to the rice transcriptome at steady
      state that leads to activation of a defense response against the blast fungus in
      rice plants. 

PMID- 24892525
TI  - Synthesis, structural investigation, DNA and protein binding study of some 3d
      metal complexes with N'-(phenyl-pyridin-2-yl-methylene)-thiophene-2-carboxylic
      acid hydrazide.
AB  - The ligand, N'-(phenyl-pyridin-2-yl-methylene)-thiophene-2-carboxylic acid
      hydrazide (Hpmtc) derived from thiophene-2-carboxylic acid hydrazide and 2
      benzoyl pyridine, and its metal complexes with Co(II), Ni(II), Cu(II) and Zn(II)
      have been synthesized. These compounds are characterized by elemental analyses,
      magnetic susceptibility measurements, IR, NMR and UV-Vis spectral studies. The
      molecular structures of Hpmtc and its Co(II) (1), Ni(II) (2), Cu(II) (3) and
      Zn(II) (4) complexes are finally determined by X-ray crystallography. Various
      spectral and single-crystal X-ray diffraction studies suggest that Hpmtc
      coordinates with metal ions as a monobasic tridentate ligand forming mononuclear
      distorted octahedral complexes of the type [M(pmtc)2]. The molecular structures
      of the complexes are stabilized by CH?N, CH?O intermolecular H-bonding, and CH?pi
      and pi?pi interactions. The DNA binding experiment of the complexes 1, 3 and 4 by
      UV-Vis absorption, and EB-DNA displacement by fluorescence spectroscopy, reveal
      an intercalative mode of binding between CT-DNA (calf-thymus DNA) and the metal
      complexes. These complexes exhibit a moderate ability to cleave pBR322 plasmid
      DNA. A comparative bovine serum albumin (BSA) protein binding activity of the
      complexes 1, 3 and 4 has also been determined by UV-Vis absorption and
      fluorescence spectroscopy. The DNA binding and protein binding studies suggest
      that the complex 3 exhibits more effective binding activity (Kb=5.54*10(5) and
      Kq=1.26*10(6) M(-1), respectively) than complexes 1 and 4. However, the complex 1
      shows better hydrolytic DNA cleavage activity compared to 3 and 4 complexes.

PMID- 24892526
TI  - Absorption spectra and photovoltaic characterization of chlorophyllins as
      sensitizers for dye-sensitized solar cells.
AB  - Dye-sensitized solar cells (DSSCs) based on Chlorine-e6 (Chl-e6), a Chlorophyll a
      derivative, and Chl-e6 containing Cu, have been investigated by carrying out
      incident photon to current efficiency (IPCE) and current-voltage (I-V)
      measurements. The effect of the metallic ion and the influence of the solvent
      polarity on the dye aggregation and their absorption bands have been analysed by
      performing electronic absorption measurements. The dependence of the
      photoelectrochemical parameters of these DSSCs on the electrolyte by the addition
      of pyrimidine and/or pyrrole has been discussed in details. For the first time I
      V curves for a DSSC based on copper Chl-e6 dye have been shown and compared with
      Zn based chlorophyllin. Furthermore, the performance of a Cu-Chl-e6 based DSSC
      has been deeply improved by a progressive optimization of the TiO2 multilayer
      photoanode overcoming the best data reported in literature so far for this dye.
      It's worth to emphasize that, the analysis reported in this paper supplies very
      useful information which paves the way to further detailed studies turned to the
      employment of natural pigments as sensitizers for solar cells. 

PMID- 24892524
TI  - Hydroxyapatite grafted carbon nanotubes and graphene nanosheets: promising bone
      implant materials.
AB  - In the present study, hydroxyapatite (HA) was successfully grafted to
      carboxylated carbon nanotubes (CNTs) and graphene nanosheets. The HA grafted CNTs
      and HA-graphene nanosheets were characterized using FT-IR, TGA, SEM and X-ray
      diffraction. The HA grafted CNTs and graphene nanosheets (CNTs-HA and Gr-HA) were
      further used to examine the proliferation and differentiation rate of temperature
      sensitive human fetal osteoblastic cell line (hFOB 1.19). Total protein assays
      and western blot analysis of osteocalcin expression were used as indicators of
      cell proliferation and differentiation. Results indicated that hFOB 1.19 cells
      proliferate and differentiate well in treatment media containing CNTs-HA and
      graphene-HA. Both CNTs-HA and graphene-HA could be promising nanomaterials for
      use as scaffolds in bone tissue engineering. 

PMID- 24892527
TI  - Theoretical investigations on the molecular structure, vibrational spectral, HOMO
      LUMO and NBO analysis of 9-[3-(Dimethylamino)propyl]-2-trifluoro-methyl-9H
      thioxanthen-9-ol.
AB  - The experimental FT-IR and FT-Raman spectra of 9-[3-(Dimethylamino)propyl]-2
      trifluoro-methyl-9H-thioxanthen-9-ol have been recorded. Quantum chemical
      calculations of geometry and vibrational wavenumbers of 9-[3
      (Dimethylamino)propyl]-2-trifluoro-methyl-9H-thioxanthen-9-ol are carried out
      theoretically. Four possible stable conformations of the title compound were
      determined. In terms of the conformational analysis, one of the most interesting
      structural features of the title compound is the intra molecular OH?N hydrogen
      bond. The barrier of planarity between the most stable and planar form is also
      predicted. The optimized geometrical parameters obtained by B3LYP method show a
      good agreement with XRD data. The difference between the observed and theoretical
      wavenumbers is very small. The complete assignments were performed on the basis
      of potential energy distribution of the vibrational modes calculated
      theoretically. The calculated HOMO and LUMO energies allow the calculation of
      atomic and molecular properties and they also showed that charge transfer occurs
      in the molecule. A detailed molecular picture of the title compound and its
      interactions were obtained from NBO analysis. As seen from the MEP map, negative
      potential regions are over the hydroxyl group and positive potential regions are
      over the methyl groups. 

PMID- 24892529
TI  - Non-destructive micro-analytical differentiation of copper pigments in paint
      layers of works of art using laboratory-based techniques.
AB  - An unambiguous identification of pigments in paint layers of works of art forms a
      substantial part of the description of a painting technique, which is essential
      for the evaluation of the work of art including determination of the period
      and/or region of its creation as well as its attribution to a workshop or an
      author. Copper pigments represent a significant group of materials used in
      historic paintings. Because of their substantial diversity and, on the other
      hand, similarity, their identification and differentiation is a challenging task.
      An analytical procedure for unambiguous determination of both mineral-type
      (azurite, malachite, posnjakite, atacamite, etc.) and verdigris-type (copper
      acetates) copper pigments in the paint layers is presented, including light
      microscopy under VIS and UV light, electron microscopy with elemental
      microanalysis, Fourier transformed infrared micro-spectroscopy (micro-FTIR), and
      X-ray powder micro-diffraction (micro-XRD). Micro-Raman measurements were largely
      hindered by fluorescence. The choice of the analytical methods meets the
      contemporary requirement of a detailed description of various components in
      heterogeneous and minute samples of paint layers without their destruction. It is
      beneficial to use the combination of phase sensitive methods such as micro-FTIR
      and micro-XRD, because it allows the identification of both mineral-type and
      verdigris-type copper pigments in one paint layer. In addition, preliminary
      results concerning the study of the loss of crystallinity of verdigris-type
      pigments in proteinaceous binding media and the effect of lead white and lead tin
      yellow as highly absorbing matrix on verdigris identification in paint layers are
      reported. 

PMID- 24892528
TI  - Electrochemical and spectroscopic characteristics of p-acryloyloxybenzoyl
      chloride and p-acryloyloxybenzoic acid and antimicrobial activity of organic
      compounds.
AB  - The purpose of this multidisciplinary work is to characterize title compounds, p
      acryloyloxybenzoyl chloride (ABC) and p-acryloyloxybenzoic acid (ABA) by means of
      experimental and theoretical evidences. As experimental research, Fourier
      transformation-infrared spectra (in the region 400-4000 cm(-1)) and nuclear
      magnetic resonance (NMR) chemical shifts (with a frequency of 400 MHz) are
      examined for spectroscopic properties belonging to the new synthesized compounds.
      Moreover, the compounds are investigated for antimicrobial activity against
      various microorganisms (Gram-positive and Gram-negative) by means of the visual
      inhibition zone technique on the agar media. The experimental results observed
      indicate that ABA exhibits more powerful inhibitors of microorganisms due to the
      presence of the hydroxyl group leading to higher reactive system, one of the most
      striking features of the paper. As for the theoretical studies, the optimized
      molecular structures, vibrational frequencies, corresponding vibrational spectra
      interpreted with the aid of normal coordinate analysis based on scaled density
      functional force field, atomic charges, thermodynamic properties at different
      temperature, 1H NMR chemical shifts by way of density functional theory (DFT)
      with the standard (B3LYP) methods at 6-311G++(d,p) basis set combination for the
      first time. According to findings, the 1H NMR chemical shifts and vibrational
      frequencies are obtained to be in good agreement with the suitable experimental
      results. Thus, it would be more precise to say that the calculation level chosen
      is powerful approach for understanding in the identification of the molecules
      investigated. At the same time, we determine the electrochemical characteristics
      belonging to the samples via the simulation of translation energy (HOMO-LUMO),
      molecular electrostatic potential (MEP) and electrostatic potential (ESP)
      investigations. It is observed that the strong intra-molecular charge transfer
      (ICT) appears between the donor and acceptor in the both compounds (especially
      ABA) due to the existence of the strong electronic donating groups and effective
      pi-pi* conjugated segments with high electronic donor ability for the
      electrophilic attack (intermolecular interactions).

PMID- 24892530
TI  - Effect of L-aspartic acid on the growth, structure and spectral studies of Zinc
      (tris) Thiourea Sulphate (ZTS) single crystals.
AB  - Single crystals of pure and L-aspartic acid doped Zinc (Tris) Thiourea Sulphate
      (ZTS) were grown from aqueous solution by solution growth method. The cell
      parameters and structure of the grown crystals were determined by X-ray
      diffraction studies. The presence of functional group in the compound has been
      confirmed by FTIR and FT-Raman analysis. The optical transparency range has been
      studied through UV-Vis spectroscopy. TGA/DTA studies show thermal stability of
      the grown crystals. Microhardness study reveals that the hardness number (Hv)
      increases with load for pure and doped ZTS crystals. Dielectric studies have been
      carried out and the results are discussed. The second harmonic generation was
      confirmed for l-aspartic acid doped ZTS which is greater than pure ZTS.

PMID- 24892531
TI  - The network modifier and former role of the bismuth ions in the bismuth-lead
      germanate glasses.
AB  - The present work is focused on the enhancement of network former environment in
      lead-germanate glasses by bismuth ions doping. A series of bismuth-lead-germanate
      glasses with the xBi2O3.(100-x)[7GeO2.3PbO] composition glass where 0<=x<=30 mol%
      Bi2O3 were synthesized by melt-quenching method. The FTIR, UV-VIS spectroscopy
      and cyclic voltammetry were conducted on these samples to evaluate the doping
      effect of structure of the host matrix network. Our results indicate that direct
      incorporation of Bi2O3 into the lead-germanate network modifies the lead
      germanate network and the internal structure of glass network is rearranged. The
      structural flexibility of the lead-germanate network is possible due to its
      incapacity to accommodate with the excess of oxygen atoms and the creation of
      bridging oxygen ions. Optical gap energy and refractive index were obtained as a
      function of Bi2O3 content. Gap energy values decrease as Bi2O3 content increased
      from 0 to 10 mol%. Further increase of Bi2O3 concentration beyond 10 mol%
      increased the gap energy values. These behaviors of the glass system can be
      explained by two mechanisms: (i) for x<=10 mol% Bi2O3--increase of degree of
      disorder of the host matrix because Bi2O3 is network modifier and (ii) for x>10
      mol%--Bi2O3 acts as a network former. Cyclic voltammetry measurements using the
      glass system with 10Bi2O3.90[7GeO2.3PbO] composition as working electrode show
      the mobility of the lead ions, in agreement with UV-VIS data.

PMID- 24892532
TI  - Comparative vibrational spectroscopic studies, HOMO-LUMO, NBO analyses and
      thermodynamic functions of p-cresol and 2-methyl-p-cresol based on DFT
      calculations.
AB  - In the present study structural properties of p-cresol, and 2-methoxy-p-cresol
      have been studied by using B3LYP/cc-pvdz and B3PW91/cc-pvdz of Density Functional
      Theory (DFT) utilizing Becke three exchange functional and Lee Yang Paar
      correlation functional. The Fourier transform infrared and Fourier transform
      Raman spectra of title molecules were recorded (solid phase). Optimized geometry,
      harmonic vibrational frequencies and various thermodynamic parameters of the
      title compounds were calculated with B3LYP/cc-pvdz, and B3PW91/cc-pvdz basis
      sets. Non-linear optical (NLO) behavior of the p-cresol and 2-methoxy-p-cresol
      were investigated by determining of electric dipole moment, polarizability alpha,
      and hyperpolarizability beta using the above mentioned basis sets. The molecular
      properties such as ionization potential, electronegativity, chemical potential,
      electrophilicity have been deduced from HOMO-LUMO analysis employing the same
      basis sets. A detailed interpretation of the infrared and Raman spectra of title
      molecules were reported. UV spectrum was measured in different solvent. The
      energy and oscillator strength are calculated by Time Dependant Density
      Functional Theory (TD-DFT) results. The calculated HOMO and LUMO energies also
      confirm that charge transfer occurs within the molecule. The complete assignments
      were performed on the basis of the potential energy distribution (PED) of
      vibrational modes, calculated with scaled quantum mechanics (SQM) method. Finally
      the theoretical FT-IR, FT-Raman, and UV spectra of the title molecules have also
      been constructed. 

PMID- 24892534
TI  - Crystal structure and DFT calculations of 5-(4-Chlorophenyl)-1-(6
      methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic acid.
AB  - The title compound, 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3
      carboxylic acid, has been characterized by using elemental analysis, MS, FT-IR,
      1H NMR and 13C NMR spectroscopic, and crystallographic techniques. The title
      compound crystallizes in the triclinic space group P-1 with a=9.612(1),
      b=9.894(1), c=17.380(1)A, alpha=90.213(5) degrees , beta=104.99(1) degrees ,
      gamma=111.072(5) degrees , V=1481.3(2)A3 and Dx=1.483 g cm(-3) respectively. The
      structure of the compound has also been examined by using quantum chemical
      methods. The molecular geometry and vibrational frequencies of monomeric and
      dimeric form of the title compound in the ground state have been calculated by
      using the B3LYP/6-31G(d,p) level of the theory. The calculated results show that
      the optimized geometry and the theoretical vibration frequencies of the dimeric
      form are good agreement with experimental data. In addition, HOMO-LUMO energy
      gap, molecular electrostatic potential map, thermodynamic properties of the title
      compound were performed at B3LYP/6-31G(d,p) level of theory.

PMID- 24892533
TI  - Synthesis, structure and excitation wavelength dependent PL properties of novel
      nanocomposite La2O2CO3.CuO.ZnO.
AB  - A novel multi-metal nanocomposite, La2O2CO3.CuO.ZnO has been synthesized by co
      precipitation method and characterized by XRD, SEM, EDS and PL spectra. XRD
      showed the presence of La2O2CO3, CuO and ZnO phases with an average particle size
      of 20 nm. Excitation at different wavelengths showed PL in UV and visible
      regions. Excitation at 220-270 nm provided UV emissions. Excitations at 298, 324
      and 355 nm showed PL in the violet and blue regions. Excitation at 395 and 450 nm
      provided green and red luminescence, respectively. It has been found that PL
      behavior of La2O2CO3.CuO.ZnO is excitation wavelength dependent. This PL property
      is contrary to well-known Kasha's rule of excitation wavelength dependence of
      emission spectrum. The excitation peaks at 300-325 (broad band), 353, 371, 394,
      408 nm were observed when monitored at 450 nm.

PMID- 24892535
TI  - Luminescent properties of orange emissive Sm3+-activated thermally stable
      phosphate phosphor for optical devices.
AB  - Rare earth ion activated orthophosphates have a great deal of interest due to
      their thermal stability for white light emitting diodes. In this regard,
      thermally stable Sm3+ doped NaCaPO4 (NCP) phosphor was synthesized by
      conventional solid state reaction technique. The phase and the structure of the
      as prepared powders were characterized by X-ray diffraction (XRD), field emission
      scanning electron microscope (FE-SEM), FT-IR, emission and excitation properties
      were extensively investigated for NCP phosphors. X-ray diffraction analysis
      confirmed the formation of NaCaPO4 with orthorhombic structure. The excitation
      spectra indicate that this phosphor can be effectively excited by UV light from
      350 to 500 nm. All the transitions in the excitation spectrum of Sm3+ start from
      the ground state 6H5/2 to various excited states. The emission spectra indicated
      that the emitted radiation was dominated by the emission peak wavelength at 599
      nm originated from the transition of 4G5/2->6H7/2. The optimum concentration of
      Sm3+ is determined as 1.0 mol% based on the concentration dependent emission
      spectra. These results suggest that the NaCaPO4:Sm3+ phosphor is a promising
      orange emitting phosphor under 404 nm excitation with CIE coordinates of x=0.545,
      y=0.41, which might be used in the development of materials for LED's and other
      optical devices in the visible region.

PMID- 24892536
TI  - Molecular structure, vibrational and electronic properties of 4-Phenyl-3H-1,3
      thiazol-2-ol using density functional theory and comparison of drug efficacy of
      keto and enol forms by QSAR analysis.
AB  - 4-Phenyl-3H-1,3-thiazol-2-ol can exist in two tautomeric forms - keto and enol.
      Comprehensive investigation of molecular geometry and electronic structure in
      ground as well as in the first excited state of 4-Phenyl-3H-1,3-thiazol-2-ol
      (enol) has been carried out. To determine lowest-energy molecular conformation of
      the title molecule, the selected torsion angles were varied in steps of 10
      degrees  and molecular energy profile was calculated from -180 degrees  to +180
      degrees . Experimental FT-IR and FT-Raman spectra of title compound were compared
      with the spectral data obtained by DFT/B3LYP method. Dipole moment,
      polarizability, first static hyperpolarizability and molecular electrostatic
      potential surface map have been calculated to get a better insight of the
      properties of title molecule. Natural bond orbital (NBO) analysis has been done
      to study the stability of the molecule arising from charge delocalization. UV-Vis
      spectrum of the title compound was also recorded and electronic properties such
      as frontier orbitals and band gap energies were calculated by TD-DFT approach. To
      compare the drug efficacy of enolic and keto forms, QSAR properties of both forms
      have also been computed and discussed. 

PMID- 24892537
TI  - Towards further understanding on the antioxidative activities of Prunus persica
      fruit: a comparative study with four different fractions.
AB  - In the present study we have evaluated the antioxidant activities of different
      fractions (hexane, ethyl acetate, n-butanol and aqueous fractions) of Prunus
      persica fruit. For extraction simple warring blender method was employed and
      total phenolic and flavonoid contents were correlated with different antioxidant
      activities (total antioxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2
      scavenging, superoxide radical scavenging, iron chelating and their reducing
      power properties). Different in vitro antioxidant studies showed that ethyl
      acetate and n-butanol fractions had the maximum activities that were well
      correlated with total phenolic and flavonoid contents. Maximum yield (25.14+/
      2.2%) was obtained in its aqueous fraction. Both ethyl acetate and n-butanol
      fractions showed significant inhibitory effects on different antioxidant
      activities. A significantly high correlation coefficient existed between total
      antioxidant activities and with total phenolic as well as total flavonoid
      contents. It appears that ethyl acetate and n-butanol fractions of P. persica may
      serve as new potential sources of natural antioxidants and could be of
      therapeutic use in treating several diseases. 

PMID- 24892538
TI  - Synthesis, crystal structure and spectral properties of a supramolecular
      trinuclear nickel(II) complex with 5-methoxy-4'-bromo-2,2'
      [ethylenedioxybis(nitrilomethylidyne)]diphenol.
AB  - A novel trinuclear Ni(II) complex [{NiL(n-PrOH)(MU-OAc)}2Ni].n-PrOH.H2O with an
      asymmetric Salamo-type ligand, 5-methoxy-4'-bromo-2,2'
      [ethylenedioxybis(nitrilomethylidyne)]diphenol (H2L), has been synthesized and
      characterized by elemental analyses, IR, UV/Vis and fluorescence spectra and
      molar conductance measurement. The crystal structure of the Ni(II) complex has
      been determined by single-crystal X-ray diffraction. Two acetate groups
      coordinating to three Ni(II) ions through NiOCONi bridges and four MU-phenoxo
      oxygen atoms from two [NiL(n-PrOH)] units also coordinating to Ni(II) ions. In
      the Ni(II) complex, two n-propanol molecules are coordinated to the two terminal
      Ni(II) ions having slightly distorted octahedral coordination geometries and form
      a trinuclear structure, There are also one non-coordinated n-propanol and one non
      coordinated water molecule. In the crystal structure, the Ni(II) complex is
      linked by intermolecular hydrogen bonds into an infinite 1D supramolecular chain
      like structure. 

PMID- 24892539
TI  - Preparation, purification and characterization of high purity multi-wall carbon
      nanotube.
AB  - Chemical vapor deposition (CVD) was optimized in order to prepare multi-wall
      carbon nanotubes (MWCNTs). Preparation of MWCNTs was achieved by the help of
      ferrocene as a catalyst with continuous flow of xylene. Morphology and structure
      of as grown and purified MWCNTs were characterized by Scanning Electron
      Microscope (SEM) and High-Resolution Transmission Electron Microscope (HRTEM).
      Energy Dispersive X-ray (EDX) spectra for the as grown MWCNTs confirm that the
      deposits are carbonaceous materials. XRD pattern of purified sample indicates
      that the Fe peaks at 44.6 and 50.9 have been decreased. This confirms that
      purification process is effectively reducing Fe component. Further qualitative
      information on the purification process are indicated and confirmed by the
      thermal analysis measurements. Finally, FTIR studies have been performed for the
      identification of the functional group attached on the surface of the MWCNTs.
      Collecting these results revealed that the optimized CVD is suitable for the
      production of MWCNTs. 

PMID- 24892540
TI  - Structural and optical properties of Eu3+, Sm3+ co-doped La(OH)3 nano-crystalline
      red emitting phosphor.
AB  - We report Eu3+, Sm3+ co-doped La(OH)3 nano-crystalline red emitting phosphor
      prepared following combustion synthesis protocol. The structural and
      morphological information about the synthesized samples have been explored using
      X-ray diffraction (XRD) and transmission electron microscopic (TEM) techniques.
      The optical properties of the samples have been investigated under 355 nm laser
      excitations. The sample emits intense red emissions at 625 and 707 nm due to 5D0
      >7F2 and 5D0->7F4 transitions in Eu3+ ion, respectively. The concentrations of
      both, Eu3+ and Sm3+ in the samples were optimized at 1 mol% to get maximum
      fluorescence. The presence of Sm3+ in the Eu3+ doped sample enhances the emission
      intensity up to two times. The samples annealed at higher temperature show
      significant enhancement in the emission intensity. The life time studies show an
      efficient energy transfer from Sm3+ to Eu3+ ions and have been discussed with the
      help of schematic energy level diagram. This enhancement in the emission
      intensity is discussed in terms of the rare earth ion concentration, annealing
      temperature and energy transfer.

PMID- 24892541
TI  - Coordination behavior and bio-potent aspects of Ni(II) with 2-aminobenzamide and
      some amino acid mixed ligands--Part II: Synthesis, spectral, morphological,
      pharmacological and DNA interaction studies.
AB  - A series of novel bioactive mixed ligand Ni(II) complexes (1a-1d) have been
      synthesised by using 2-aminobenzamide (2AB) and some bio-relevant amino acid
      ligands. The synthesised Ni(II) complexes were structurally characterized by
      various physico-chemical and spectral studies. Elemental analysis and molar
      conductance values suggest that 1:1:1 stoichiometry with non-electrolytic nature.
      Based on the spectral studies, both the ligands act as bidentate and they chelate
      with Ni(II) ion via amino-NH2 and amido-O and deprotonated carboxylato-O and
      amino-NH2 atoms respectively to form a stable six, five membered chelate rings
      with mononuclear octahedral geometry. Thermal studies show the presence of
      coordinated water and acetate molecules in the coordination. The powder X-ray
      diffractogram and SEM pictograph imply that all the complexes have fine
      crystalline peaks with homogeneous surface morphology. In vitro antimicrobial and
      antioxidant studies indicate the complexes are more active than free 2
      aminobenzamide ligand. The Ni(II)-2AB-gly/phe complexes (1a and 1d) show
      significant oxidative cleavage and DNA binding activities. Moreover, the 3D
      molecular modeling, analysis of the complexes has also been studied. 

PMID- 24892542
TI  - Study of conformational stability, structural, electronic and charge transfer
      properties of cladrin using vibrational spectroscopy and DFT calculations.
AB  - In the present work, a detailed conformational study of cladrin (3-(3,4-dimethoxy
      phenyl)-7-hydroxychromen-4-one) has been done by using spectroscopic techniques
      (FT-IR/FT-Raman/UV-Vis/NMR) and quantum chemical calculations. The optimized
      geometry, wavenumber and intensity of the vibrational bands of the cladrin in
      ground state were calculated by density functional theory (DFT) employing 6
      311++G(d,p) basis sets. The study has been focused on the two most stable
      conformers that are selected after the full geometry optimization of the
      molecule. A detailed assignment of the FT-IR and FT-Raman spectra has been done
      for both the conformers along with potential energy distribution for each
      vibrational mode. The observed and scaled wavenumber of most of the bands has
      been found to be in good agreement. The UV-Vis spectrum has been recorded and
      compared with calculated spectrum. In addition, 1H and 13C nuclear magnetic
      resonance spectra have been also recorded and compared with the calculated data
      that shows the inter or intramolecular hydrogen bonding. The electronic
      properties such as HOMO-LUMO energies were calculated by using time-dependent
      density functional theory. Molecular electrostatic potential has been plotted to
      elucidate the reactive part of the molecule. Natural bond orbital analysis was
      performed to investigate the molecular stability. Non linear optical property of
      the molecule have been studied by calculating the electric dipole moment (MU) and
      the first hyperpolarizability (beta) that results in the nonlinearity of the
      molecule.

PMID- 24892544
TI  - Spectroscopic and fiber optic ethanol sensing properties Gd doped ZnO
      nanoparticles.
AB  - We report the structural, optical and gas sensing properties of prepared pure and
      Gd doped ZnO nanoparticles through solgel method at moderate temperature.
      Structural studies are carried out by X-ray diffraction method confirms hexagonal
      wurtzite structure and doping induced changes in lattice parameters is observed.
      Optical absorption spectral studies shows red shift in the absorption peak
      corresponds to band-gap from 3.42 eV to 3.05 eV and broad absorption in the
      visible range after Gd doping is observed. Scanning electron microscopic studies
      shows increase in particle size where the particle diameters increase from few nm
      to micrometers after Gd doping. The clad modified ethanol fiber-optic sensor
      studies for ethanol sensing exhibits best sensitivity for the 3% Gd doped ZnO
      nanoparticles and the sensitivity get lowered incase of higher percentage of Gd
      doped ZnO sample.

PMID- 24892543
TI  - Enhanced chemiluminescence CdSe quantum dots by histidine and tryptophan.
AB  - The enhancing effect of histidine and tryptophan on chemiluminescence (CL) of
      CdSe quantum dots (QDs)-H2O2 system was studied. This reaction is based on the
      catalytic effect of amino acids, causing a significant increase in the light
      emission, as a result of the reaction of quantum dots (QDs) with hydrogen
      peroxide. In the optimum conditions, this method was satisfactorily described by
      linear calibration curve in the range of 0.66-35.5 MUM and 0.83-35.1 MUM for
      histidine and tryptophan, respectively. The effect of various parameters such as
      concentration of CdSe QDs, concentration of H2O2 and concentration of imidazole
      on the intensity of CL system were studied. The main experimental advantage of
      the proposed method is it's selective to two amino acids compared with other
      amino acids.

PMID- 24892545
TI  - Artificial neural network and particle swarm optimization for removal of methyl
      orange by gold nanoparticles loaded on activated carbon and Tamarisk.
AB  - The influence of variables, namely initial dye concentration, adsorbent dosage
      (g), stirrer speed (rpm) and contact time (min) on the removal of methyl orange
      (MO) by gold nanoparticles loaded on activated carbon (Au-NP-AC) and Tamarisk
      were investigated using multiple linear regression (MLR) and artificial neural
      network (ANN) and the variables were optimized by partial swarm optimization
      (PSO). Comparison of the results achieved using proposed models, showed the ANN
      model was better than the MLR model for prediction of methyl orange removal using
      Au-NP-AC and Tamarisk. Using the optimal ANN model the coefficient of
      determination (R2) for the test data set were 0.958 and 0.989; mean squared error
      (MSE) values were 0.00082 and 0.0006 for Au-NP-AC and Tamarisk adsorbent,
      respectively. In this study a novel and green approach were reported for the
      synthesis of gold nanoparticle and activated carbon by Tamarisk. This material
      was characterized using different techniques such as SEM, TEM, XRD and BET. The
      usability of Au-NP-AC and activated carbon (AC) Tamarisk for the methyl orange
      from aqueous solutions was investigated. The effect of variables such as pH,
      initial dye concentration, adsorbent dosage (g) and contact time (min) on methyl
      orange removal were studied. Fitting the experimental equilibrium data to various
      isotherm models such as Langmuir, Freundlich, Tempkin and Dubinin-Radushkevich
      models show the suitability and applicability of the Langmuir model. Kinetic
      models such as pseudo-first order, pseudo-second order, Elovich and intraparticle
      diffusion models indicate that the second-order equation and intraparticle
      diffusion models control the kinetic of the adsorption process. The small amount
      of proposed Au-NP-AC and activated carbon (0.015 g and 0.75 g) is applicable for
      successful removal of methyl orange (>98%) in short time (20 min for Au-NP-AC and
      45 min for Tamarisk-AC) with high adsorption capacity 161 mg g(-1) for Au-NP-AC
      and 3.84 mg g(-1) for Tamarisk-AC.

PMID- 24892546
TI  - Kinetic study and mechanism of Niclosamide degradation.
AB  - A spectrophotometric kinetic study of Niclosamide alkaline degradation as a
      function of drug concentration, alkaline concentration and temperature has been
      established utilizing double divisor-ratio spectra spectrophotometric method. The
      developed method allowed determination of Niclosamide in presence of its alkaline
      degradation products; namely; 2-chloro-4-nitro aniline (DEG I) and 5-chloro
      salicylic acid (DEG II) with characterization of its degradation mechanism. It
      was found that degradation kinetic of Niclosamide followed pseudo-first order
      under the established experimental conditions with a degradation rate constant
      (k) of 0.0829 mol/h and half life (t1/2) of 8.35 h. The overall degradation rate
      constant as a function of the temperature under the given conditions obeyed
      Arrhenius equation where the activation energy was calculated to be 3.41
      kcal/mol.

PMID- 24892547
TI  - Transition metal complexes of a new 15-membered [N5] penta-azamacrocyclic ligand
      with their spectral and anticancer studies.
AB  - Novel penta-azamacrocyclic 15-membered [N5] ligand [L] i.e. 1,5,8,12-tetetraaza
      3,4: 9,10-dibenzo-6-ethyl-7-methyl-1,12-(2,6-pyrido)cyclopentadecan-5,7 diene
      2,11-dione and its transition metal complexes with Co(II), Ni(II), Cu(II),
      Ru(III) and Pd(II) have been synthesized and structurally characterized by
      elemental analysis, spectral, thermal as well as magnetic and molar conductivity
      measurements. On basis of IR, MS, UV-Vis 1H NMR and EPR spectral studies an
      octahedral geometry has been proposed for all complexes except Co(II), Cu(II)
      nitrate complexes and Pd(II) chloride complex that adopt tetrahedral, square
      pyramidal and square planar geometries, respectively. The antitumor activity of
      the synthesized ligand and some complexes against human breast cancer cell lines
      (MCF-7) and human hepatocarcinoma cell lines (HepG2) has been studied. The
      complexes (IC50=2.04-9.7, 2.5-3.7 MUg/mL) showed potent antitumor activity
      comparable with their ligand (IC50=11.7, 3.45 MUg/mL) against the above mentioned
      cell lines, respectively. The results evidently show that the activity of the
      ligand becomes more pronounced and significant when coordinated to the metal ion.

PMID- 24892548
TI  - Directed evolution of human heavy chain variable domain (VH) using in vivo
      protein fitness filter.
AB  - Human immunoglobulin heavy chain variable domains (VH) are promising scaffolds
      for antigen binding. However, VH is an unstable and aggregation-prone protein,
      hindering its use for therapeutic purposes. To evolve the VH domain, we performed
      in vivo protein solubility selection that linked antibiotic resistance to the
      protein folding quality control mechanism of the twin-arginine translocation
      pathway of E. coli. After screening a human germ-line VH library, 95% of the VH
      proteins obtained were identified as VH3 family members; one VH protein, MG2x1,
      stood out among separate clones expressing individual VH variants. With further
      screening of combinatorial framework mutation library of MG2x1, we found a
      consistent bias toward substitution with tryptophan at the position of 50 and 58
      in VH. Comparison of the crystal structures of the VH variants revealed that
      those substitutions with bulky side chain amino acids filled the cavity in the VH
      interface between heavy and light chains of the Fab arrangement along with the
      increased number of hydrogen bonds, decreased solvation energy, and increased
      negative charge. Accordingly, the engineered VH acquires an increased level of
      thermodynamic stability, reversible folding, and soluble expression. The library
      built with the VH variant as a scaffold was qualified as most of VH clones
      selected randomly were expressed as soluble form in E. coli regardless length of
      the combinatorial CDR. Furthermore, a non-aggregation feature of the selected VH
      conferred a free of humoral response in mice, even when administered together
      with adjuvant. As a result, this selection provides an alternative directed
      evolution pathway for unstable proteins, which are distinct from conventional
      methods based on the phage display. 

PMID- 24892552
TI  - Modeling acclimatization by hybrid systems: condition changes alter biological
      system behavior models.
AB  - In order to describe the dynamic behavior of a complex biological system, it is
      useful to combine models integrating processes at different levels and with
      temporal dependencies. Such combinations are necessary for modeling
      acclimatization, a phenomenon where changes in environmental conditions can
      induce drastic changes in the behavior of a biological system. In this article we
      formalize the use of hybrid systems as a tool to model this kind of biological
      behavior. A modeling scheme called strong switches is proposed. It allows one to
      take into account both minor adjustments to the coefficients of a continuous
      model, and, more interestingly, large-scale changes to the structure of the
      model. We illustrate the proposed methodology with two applications:
      acclimatization in wine fermentation kinetics, and acclimatization of osteo-adipo
      differentiation system linking stimulus signals to bone mass. 

PMID- 24892551
TI  - Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular
      carcinoma.
AB  - We sought to identify a secreted biomarker for beta-catenin activation commonly
      seen in hepatocellular carcinoma (HCC). By examination of our previously
      published genearray of hepatocyte-specific beta-catenin knockout (KO) livers, we
      identified secreted factors whose expression may be beta-catenin-dependent. We
      verified expression and secretion of the leading factor in HCC cells transfected
      with mutated (Hep3BS33Y)-beta-catenin. Serum levels of biomarker were next
      investigated in a mouse model of HCC with beta-catenin gene (Ctnnb1) mutations
      and eventually in HCC patients. Leukocyte cell-derived chemotaxin-2 (LECT2)
      expression was decreased in KO livers. Hep3BS33Y expressed and secreted more
      LECT2 in media as compared to Hep3BWT. Mice developing HCC with Ctnnb1 mutations
      showed significantly higher serum LECT2 levels. However patients with CTNNB1
      mutations showed LECT2 levels of 54.28 +/- 22.32 ng/mL (Mean +/- SD; n = 8) that
      were insignificantly different from patients with non-neoplastic chronic liver
      disease (32.8 +/- 21.1 ng/mL; n = 15) or healthy volunteers (33.2 +/- 7.2 ng/mL;
      n = 11). Intriguingly, patients without beta-catenin mutations showed
      significantly higher serum LECT2 levels (54.26 +/- 22.25 ng/mL; n = 46). While
      beta-catenin activation was evident in a subset of non-mutant beta-catenin HCC
      group with high LECT2 expression, serum LECT2 was unequivocally similar between
      beta-catenin-active and -normal group. Further analysis showed that LECT2 levels
      greater than 50 ng/ml diagnosed HCC in patients irrespective of beta-catenin
      mutations with specificity of 96.1% and positive predictive value of 97.0%. Thus,
      LECT2 is regulated by beta-catenin in HCC in both mice and men, but serum LECT2
      reflects beta-catenin activity only in mice. Serum LECT2 could be a potential
      biomarker of HCC in patients.

PMID- 24892549
TI  - Functional screening identifies miRNAs influencing apoptosis and proliferation in
      colorectal cancer.
AB  - MicroRNAs (miRNAs) play a critical role in many biological processes and are
      aberrantly expressed in human cancers. Particular miRNAs function either as tumor
      suppressors or oncogenes and appear to have diagnostic and prognostic
      significance. Although numerous miRNAs are dys-regulated in colorectal cancer
      (CRC) only a small fraction has been characterized functionally. Using high
      throughput functional screening and miRNA profiling of clinical samples the
      present study aims at identifying miRNAs important for the control of cellular
      growth and/or apoptosis in CRC. The high-throughput functional screening was
      carried out in six CRC cell lines transfected with a pre-miR library including
      319 synthetic human pre-miRs. Phenotypic alterations were evaluated by
      immunostaining of cleaved cPARP (apoptosis) or MKI67 (proliferation).
      Additionally, TaqMan Human MicroRNA Array Set v2.0 was used to profile the
      expression of 667 miRNAs in 14 normal colon mucosa and 46 microsatellite stable
      stage II CRC patients. Among the miRNAs that induced growth arrest and apoptosis
      in the CRC cell lines, and at same time were dys-regulated in the clinical
      samples, miR-375 was selected for further analysis. Independent in vitro analysis
      of transient and stable transfected CRC cell lines confirmed that miR-375 reduces
      cell viability through the induction of apoptotic death. We identified YAP1 as a
      direct miR-375 target in CRC and show that HELLS and NOLC1 are down-stream
      targets. Knock-down of YAP1 mimicked the phenotype induced by miR-375 over
      expression indicating that miR-375 most likely exerts its pro-apoptotic role
      through YAP1 and its anti-apoptotic down-stream targets BIRC5 and BCL2L1.
      Finally, in vivo analysis of mouse xenograft tumors showed that miR-375
      expression significantly reduced tumor growth. We conclude that the high
      throughput screening successfully identified miRNAs that induce apoptosis and/or
      inhibit proliferation in CRC cells. Finally, combining the functional screening
      with profiling of CRC tissue samples we identified clinically relevant miRNAs and
      miRNA targets in CRC. 

PMID- 24892554
TI  - Functional characterization of PMT2, encoding a protein-O-mannosyltransferase, in
      the human pathogen Cryptococcus neoformans.
AB  - Diazobenzoic acid B (DBB), also known as diazonium blue B or fast blue B, can be
      used to distinguish basidiomycetous yeasts from ascomycetes. This chemical has
      long been used for the taxonomic study of yeast species at the phylum level, but
      the mechanism underlying the DBB staining remains unknown. To identify molecular
      targets of DBB staining, we isolated Agrobacterium tumefaciens-mediated
      insertional mutants of Cryptococcus neoformans, a basidiomycetous pathogenic
      yeast, which were negative to DBB staining. In one of these mutants, we found
      that the PMT2 gene, encoding a protein-O-mannosyltransferase, was interrupted by
      a T-DNA insertion. A complete gene knockout of the PMT2 gene revealed that the
      gene was responsible for DBB staining in C. neoformans, suggesting that one of
      the targets of Pmt2-mediated glycosylation is responsible for interacting with
      DBB. We also determined that Cryptococcus gattii, a close relative of C.
      neoformans, was not stained by DBB when the PMT2 gene was deleted. Our finding
      suggests that the protein-O-mannosylation by the PMT2 gene product is required
      for DBB staining in Cryptococcus species in general. We also showed that
      glycosylation in Cryptococcus by Pmt2 plays important roles in controlling cell
      size, resistance to high temperature and osmolarity, capsule formation, sexual
      reproduction, and virulence. 

PMID- 24892553
TI  - Guanabenz interferes with ER stress and exerts protective effects in cardiac
      myocytes.
AB  - Endoplasmic reticulum (ER) stress has been implicated in a variety of
      cardiovascular diseases. During ER stress, disruption of the complex of protein
      phosphatase 1 regulatory subunit 15A and catalytic subunit of protein phosphatase
      1 by the small molecule guanabenz (antihypertensive, alpha2-adrenoceptor agonist)
      and subsequent inhibition of stress-induced dephosphorylation of eukaryotic
      translation initiation factor 2alpha (eIF2alpha) results in prolonged eIF2alpha
      phosphorylation, inhibition of protein synthesis and protection from ER stress.
      In this study we assessed whether guanabenz protects against ER stress in cardiac
      myocytes and affects the function of 3 dimensional engineered heart tissue (EHT).
      We utilized neonatal rat cardiac myocytes for the assessment of cell viability
      and activation of ER stress-signalling pathways and EHT for functional analysis.
      (i) Tunicamycin induced ER stress as measured by increased mRNA and protein
      levels of glucose-regulated protein 78 kDa, P-eIF2alpha, activating transcription
      factor 4, C/EBP homologous protein, and cell death. (ii) Guanabenz had no
      measurable effect alone, but antagonized the effects of tunicamycin on ER stress
      markers. (iii) Tunicamycin and other known inducers of ER stress (hydrogen
      peroxide, doxorubicin, thapsigargin) induced cardiac myocyte death, and this was
      antagonized by guanabenz in a concentration- and time-dependent manner. (iv) ER
      stressors also induced acute or delayed contractile dysfunction in spontaneously
      beating EHTs and this was, with the notable exception of relaxation deficits
      under thapsigargin, not significantly affected by guanabenz. The data confirm
      that guanabenz interferes with ER stress-signalling and has protective effects on
      cell survival. Data show for the first time that this concept extends to cardiac
      myocytes. The modest protection in EHTs points to more complex mechanisms of
      force regulation in intact functional heart muscle. 

PMID- 24892555
TI  - Simultaneous multi-species tracking in live cells with quantum dot conjugates.
AB  - Quantum dots are available in a range of spectrally separated emission colors and
      with a range of water-stabilizing surface coatings that offers great flexibility
      for enabling bio-specificity. In this study, we have taken advantage of this
      flexibility to demonstrate that it is possible to perform a simultaneous
      investigation of the lateral dynamics in the plasma membrane of i) the
      transmembrane epidermal growth factor receptor, ii) the
      glucosylphospatidylinositol-anchored protein CD59, and iii) ganglioside GM1
      cholera toxin subunit B clusters in a single cell. We show that a large number of
      the trajectories are longer than 50 steps, which we by simulations show to be
      sufficient for robust single trajectory analysis. This analysis shows that the
      populations of the diffusion coefficients are heterogeneously distributed for all
      three species, but differ between the different species. We further show that the
      heterogeneity is decreased upon treating the cells with methyl-beta-cyclodextrin.

PMID- 24892556
TI  - Clinical criteria replenish high-sensitive troponin and inflammatory markers in
      the stratification of patients with suspected acute coronary syndrome.
AB  - OBJECTIVES: In patients with suspected acute coronary syndrome (ACS), rapid
      triage is essential. The aim of this study was to establish a tool for risk
      prediction of 30-day cardiac events (CE) on admission. 30-day cardiac events (CE)
      were defined as early coronary revascularization, subsequent myocardial
      infarction, or cardiovascular death within 30 days. METHODS AND RESULTS: This
      single-centre, prospective cohort study included 377 consecutive patients
      presenting to the emergency department with suspected ACS and for whom troponin T
      measurements were requested on clinical grounds. Fifteen biomarkers were analyzed
      in the admission sample, and clinical parameters were assessed by the TIMI risk
      score for unstable angina/Non-ST myocardial infarction and the GRACE risk score.
      Sixty-nine (18%) patients presented with and 308 (82%) without ST-elevations,
      respectively. Coronary angiography was performed in 165 (44%) patients with
      subsequent percutaneous coronary intervention--accounting for the majority of CE-
      in 123 (33%) patients, respectively. Eleven out of 15 biomarkers were elevated in
      patients with CE compared to those without. High-sensitive troponin T (hs-cTnT)
      was the best univariate biomarker to predict CE in Non-ST-elevation patients (AUC
      0.80), but did not yield incremental information above clinical TIMI risk score
      (AUC 0.80 vs 0.82, p = 0.69). Equivalence testing of AUCs of risk models and non
      inferiority testing demonstrated that the clinical TIMI risk score alone was non
      inferior to its combination with hs-cTnT in predicting CE. CONCLUSIONS: In
      patients presenting without ST-elevations, identification of those prone to CE is
      best based on clinical assessment based on TIMI risk score criteria and hs-cTnT.

PMID- 24892557
TI  - Isolation of antiosteoporotic compounds from seeds of Sophora japonica.
AB  - Chemical investigation of Sophora japonica seeds resulted in the isolation of
      seven metabolites identified as: genistin (1), sophoricoside (2), sophorabioside
      (3), sophoraflavonoloside (4), genistein 7,4'-di-O-beta-D-glucopyransoide (5),
      kaempferol 3-O-alpha-L-rhamnopyranosyl(1 -> 6)beta-D-glucopyranosyl(1 -> 2)beta-D
      glucopyranoside (6) and rutin (7). Compounds 1, 2 and 5 showed significant
      estrogenic proliferative effect in MCF-7 cell in sub-cytotoxic concentration
      range. Compounds 1 and 2 showed minimal cell membrane damaging effect using LDH
      leakage assay. Accordingly, compound 2 (sophoricoside, (SPH)) was selected for
      further in-vivo studies as a potential anti-osteoporosis agent. The anti
      osteoporotic effect of SPH was assessed in ovarectomized (OVX) rats after oral
      administration (15 mg/kg and 30 mg/kg) for 45 days compared to estradiol (10
      ug/kg) as a positive control. Only in a dose of 30 mg/kg, SPH regained the
      original mechanical bone hardness compared to normal non-osteoporotic group.
      However, SPH (15 mg/kg) significantly increased the level of alkaline phosphatase
      (ALP) to normal level. Treatment with SPH (30 mg/kg) increased the level of ALP
      to be higher than normal group. SPH (15 mg/kg) did not significantly increase the
      serum level of osteocalcin (OC) compared to OVX group. On the other hand,
      treatment with SPH (30 mg/kg) significantly increased the level of OC to 78%
      higher than normal non-ovarectomized animals group. In addition, SPH (15 mg/kg)
      decreased the bone resorption marker, acid phosphatase (ACP) to normal level and
      SPH (30 mg/kg) further diminished the level of serum ACP. Histopathologically,
      sophoricoside ameliorated the ovarectomy induced osteoporosis in a dose dependent
      manner. The drug showed thicker bony trabeculae, more osteoid, and more
      osteoblastic rimming compared to OVX group.

PMID- 24892558
TI  - Vitamin D antagonizes negative effects of preeclampsia on fetal endothelial
      colony forming cell number and function.
AB  - CONTEXT: Endothelial dysfunction is a primary feature of preeclampsia, a
      pregnancy complication associated with an increased future cardiovascular risk
      for mother and offspring. Endothelial colony forming cells (ECFC) are endothelial
      progenitor cells that participate in vasculogenesis and endothelial repair.
      OBJECTIVE: We hypothesized that the number and functional properties of fetal
      cord blood-derived ECFCs are reduced in preeclampsia compared to uncomplicated
      pregnancy (controls), and asked if adverse effects of preeclampsia on ECFC
      function are reversed by 1,25 (OH)2 vitamin D3. DESIGN, SETTING, PATIENTS: This
      was a nested, case-control study. Forty women with uncomplicated pregnancy and 33
      women with PE were recruited at Magee-Womens Hospital (USA) or at Hannover
      Medical School (Germany). MAIN OUTCOME MEASURES: Time to ECFC colony appearance
      in culture, and number of colonies formed, were determined. Functional abilities
      of ECFCs were assessed in vitro by tubule formation in Matrigel assay, migration,
      and proliferation. ECFC function was tested in the presence or absence of 1,25
      (OH)2 vitamin D3, and after vitamin D receptor (VDR) or VEGF signaling blockade.
      RESULTS: The number of cord ECFC colonies was lower (P = 0.04) in preeclampsia
      compared to controls. ECFCs from preeclampsia showed reduced proliferation
      (P<0.0001), formed fewer tubules (P = 0.02), and migrated less (P = 0.049) than
      control. Vitamin D3 significantly improved preeclampsia ECFC functional
      properties. VDR- or VEGF blockade reduced tubule formation, partially restorable
      by vitamin D3. CONCLUSION: Fetal ECFCs from preeclamptic pregnancies are reduced
      in number and dysfunctional. Vitamin D3 had rescuing effects. This may have
      implications for the increased cardiovascular risk associated with preeclampsia.

PMID- 24892561
TI  - Target-induced aptamer release strategy based on electrochemical detection of
      staphylococcal enterotoxin B using GNPs-ZrO2-Chits film.
AB  - A novel electrochemical aptasensor was developed for ultrasensitive detection of
      staphylococcal enterotoxin B (SEB) by combining signal amplification and target
      induced aptamer release strategy. A gold electrode was modified with a
      nanocomposite made of gold nanoparticles reduced in situ, zirconia nanoparticles,
      and chitosan. The SEB aptamer was hybridized by anchoring the capture probe on
      the modified gold electrode surface through AuS binding. In the presence of SEB,
      the capture probe-aptamer duplex was compelled to open, releasing the aptamer
      from the electrode. The resulting single-strand capture probe was hybridized with
      a biotinylated detection probe and labeled with streptavidin-horseradish
      peroxidase, producing an ultrasensitive enzyme-catalyzed electrochemical signal.
      Under optimal conditions, the amperometric responses were proportional to the SEB
      concentrations ranging from 2 to 512ngmL(-1), with a detection limit of as low as
      0.24ngmL(-1) (S/N=3). The aptasensor exhibited good stability, outstanding
      reproducibility, and high selectivity. The as-prepared aptasensor was used to
      analyze SEB in human serum specimens, and validated through enzyme-linked
      immunosorbent assay method. Analytical results suggest that the developed assay
      is a promising alternative approach for detecting SEB in clinical diagnosis. 

PMID- 24892559
TI  - Genome-based discovery of a novel membrane-bound 1,6-dihydroxyphenazine
      prenyltransferase from a marine actinomycete.
AB  - Recently, novel prenylated derivatives of 1,6-dihydroxyphenazine have been
      isolated from the marine sponge-associated Streptomyces sp. SpC080624SC-11.
      Genome sequencing of this strain now revealed a gene cluster containing all genes
      necessary for the synthesis of the phenazine and the isoprenoid moieties.
      Unexpectedly, however, the cluster did not contain a gene with similarity to
      previously investigated phenazine prenyltransferases, but instead a gene with
      modest similarity to the membrane-bound prenyltransferases of ubiquinone and
      menaquinone biosynthesis. Expression of this gene in E. coli and isolation of the
      membrane fraction proved that the encoded enzyme, Mpz10, catalyzes two successive
      prenylations of 1,6-dihydroxyphenazine. Mpz10 is the first example of a membrane
      bound enzyme catalyzing the prenylation of a phenazine substrate, and one of few
      examples of membrane-bound enzymes involved in the prenylation of aromatic
      secondary metabolites in microorganisms. 

PMID- 24892560
TI  - Antidepressant sales and the risk for alcohol-related and non-alcohol-related
      suicide in Finland--an individual-level population study.
AB  - OBJECTIVES: A marked decline in suicide rates has co-occurred with increased
      antidepressant sales in several countries but the causal connection between the
      trends remains debated. Most previous studies have focused on overall suicide
      rates and neglected differential effects in population subgroups. Our objective
      was to investigate whether increasing sales of non-tricyclic antidepressants have
      reduced alcohol- and non-alcohol-related suicide risk in different population
      subgroups. METHODS: We followed a nationally representative sample of 950,158
      Finnish adults in 1995-2007 for alcohol-related (n = 2,859) and non-alcohol
      related (n = 8,632) suicides. We assessed suicide risk by gender and social group
      according to regional sales of non-tricyclic antidepressants, measured by sold
      doses per capita, prevalence of antidepressant users, and proportion of
      antidepressant users with doses reflecting minimally adequate treatment. Fixed
      effects Poisson regression models controlled for regional differences and time
      trends that may influence suicide risk irrespective of antidepressant sales.
      RESULTS: The number of sold antidepressant doses per capita and the prevalence of
      antidepressant users were unrelated to male suicide risk. However, one percentage
      point increase in the proportion of antidepressant users receiving minimally
      adequate treatment reduced non-alcohol-related male suicide risk by one percent
      (relative risk 0.987, 95% confidence interval 0.976-0.998). This beneficial
      effect only emerged among men with high education, high income, and employment,
      among men without a partner, and men not owning their home. Alcohol-related
      suicides and female suicides were unrelated to all measures of antidepressant
      sales. CONCLUSION: We found little evidence that increase in overall sales or in
      the prevalence of non-tricyclic antidepressant users would have caused the fall
      in suicide rates in Finland in 1995-2007. However, the rise in the proportion of
      antidepressant users receiving minimally adequate treatment, possibly due to
      enhanced treatment compliance, may have prevented non-alcohol-related suicides
      among men.

PMID- 24892563
TI  - Self-cleaning and self-sanitizing coatings on plastic fabrics: design,
      manufacture and performance.
AB  - Self-cleaning and self-sanitizing coatings are of utmost interest in several
      manufacturing domains. In particular, fabrics and textile materials are often pre
      treated by impregnation or incorporation with antimicrobial pesticides for
      protection purposes against bacteria and fungi that are pathogenic for man or
      other animals. In this respect, the present investigation deals with the design
      and manufacture of self-cleaning and self-sanitizing coatings on plastic fabrics.
      The functionalization of the coatings was yield by incorporating active inorganic
      matter alone (i.e., photo-catalytic TiO2 anatase and Ag(+) ions) inside an
      organic inorganic hybrid binder. The achieved formulations were deposited on
      coextruded polyvinylchloride-polyester fabrics by air-mix spraying and left to
      dry at ambient temperature. The performance of the resulting coatings were
      characterized for their self-cleaning and self-sanitizing ability according to
      standardized testing procedure and/or applicable international regulations. 

PMID- 24892562
TI  - Silk porous scaffolds with nanofibrous microstructures and tunable properties.
AB  - Scaffold biomaterials derived from silk fibroin have been widely used in tissue
      engineering. However, mimicking the nanofibrous structures of the extracellular
      matrix (ECM) for achieving better biocompatibility remains a challenge. Here, we
      design a mild self-assembly approach to prepare nanofibrous scaffolds from silk
      fibroin solution. Silk nanofibers were self-assembled by slowly concentrating
      process in aqueous solution without any cross-linker or toxic solvent and then
      were further fabricated into porous scaffolds with pore size of about 200-250MUm
      through lyophilization, mimicking nano and micro structures of ECM. Gradient
      water/methanol annealing treatments were used to control the secondary
      structures, mechanical properties, and degradation behaviors of the scaffolds,
      which would be critical for different tissue regeneration applications. With salt
      leached silk scaffold as control, the ECM-mimetic scaffolds with different
      secondary structures were used to culture the amniotic fluid-derived stem cells
      in vitro to confirm their biocompatibility. All the ECM-mimetic scaffolds with
      different secondary structures represented better cell growth and proliferation
      compared to the salt-leached scaffold, confirming the critical influence of ECM
      mimetic structure on biocompatibility. Although further studies such as cell
      differentiation behaviours are still necessary for clarifying the influence of
      microstructures and secondary conformational compositions, our study provides
      promising scaffold candidate that is suitable for different tissue regenerations.

PMID- 24892564
TI  - Hereditary Diffuse Infiltrating Retinoblastoma.
AB  - Retinoblastoma is one of the most common childhood cancers. The diffuse
      infiltrating retinoblastoma is a rare subtype of this neoplasm. The majority of
      cases of diffuse infiltrating retinoblastoma are unilateral and occur
      sporadically. Herein we report on a family with three children affected by
      retinoblastoma, among them one girl with diffuse infiltrating retinoblastoma.
      This girl was diagnosed at the age of 8 years with a unilateral diffuse
      infiltrating retinoblastoma. By contrast, the two brothers became clinically
      apparent in the first 2 years of life with bilateral retinoblastoma. The parents
      were clinically unremarkable. Genetic analysis of RB1 gene was performed. The
      girl with diffuse infiltrating RB was found to be heterozygous for an oncogenic
      mutation in the RB1 gene that was also carried by both brothers and the father of
      the family. These results show that diffuse infiltrating retinoblastoma can
      develop on the background of a hereditary predisposition to retinoblastoma. 

PMID- 24892565
TI  - Association of Lysyl Oxidase-Like 1 Gene Polymorphisms in Pseudoexfoliation
      Syndrome and Pseudoexfoliation Glaucoma in a Spanish Population.
AB  - PURPOSE: To evaluate the association of the lysyl oxidase-like 1 (LOXL1) single
      nucleotide polymorphisms (SNPs) in a Spanish population with pseudoexfoliation
      syndrome (XFS) and pseudoexfoliation glaucoma (XFG). MATERIALS AND METHODS: The
      present case-control study included 100 Spanish patients (60 patients with XFS
      and 40 patients with XFG) and 90 control subjects. Genotypes of the three single
      nucleotide polymorphisms of LOXL1 (rs1048661, rs3825942, and rs2165241) were
      analyzed with direct sequencing. RESULTS: The G allele and the GG genotype of SNP
      rs3825942 were detected at a statistically higher frequency in pseudoexfoliation
      patients than in control subjects (p = 3.36 * 10(-5), OR = 5.71, 95% CI: 2.30
      14.18; p = 3.38 * 10(-5), OR = 6.91, 95% CI: 2.51-19.03 respectively). The T
      allele and the TT genotype of SNP rs2165241 presented at significantly higher
      frequencies in pseudoexfoliation patients than in controls (p = 2.50 * 10(-4), OR
      = 2.18, 95% CI: 1.43-3.33; p = 1.21 * 10(-2), OR = 2.13, 95% CI: 1.75-3.85
      respectively). No significant association between XFS/XFG and the rs1048661 was
      observed. The GGT haplotype composed of all three risk alleles was determined to
      be significantly associated with pseudoexfoliation. The genotypic and allelic
      distributions of the three SNPs were similar between XFS and XFG. CONCLUSIONS:
      This is the first study associating two SNPs of LOXL1 (rs3825942 and rs2165241)
      and XFS/XFG in a Spanish population, confirming findings in patients from Europe.
      However rs1048661 SNP did not show an association with XFS.

PMID- 24892566
TI  - [Enteroparasitism, hygiene and environmental sanitation in under-aged from six
      indigenous communities. Cali-Colombia].
AB  - OBJECTIVE: Determine the prevalence of intestinal parasitism and associated
      factors in indigenous children between 5 and 14 years, living in the city of
      Cali, Colombia. METHODOLOGY: 63 children aged 5 to 14 were included. At least two
      fecal samples were taken to which two different tests were applied, first one
      directly and the other one for concentration: Ziehl-Neelsen modified and Kato
      Katz. In order to collect socio-demographic and epidemiological interest data, a
      survey was done. The results of the survey were compared through a process of
      observation at 50.0 % of the minors' homes. Proportions and ratios were
      calculated for qualitative variables, chi(2) and Fischer Exact Test (considering
      a value of p <= 0.05 as statistically significant) was used for quantitative
      measures of the main trend and the relation between variables. RESULTS: 84.0 % of
      the minors were infected, predominantly by protozoa 71.0 %. Over 50.0 % of those
      samples were considered as multiple parasitism; the predominant parasites were E
      histolytica/dispar (25.0 %) and the guest was Endolimax nana (60.0 %).
      Statistically significant association was observed between parasitism, abdominal
      pain (Test chi(2), p <= 0.05) and non-deworming of domestic animals (Test
      Fisher's p <= 0.05). CONCLUSIONS: The prevalence of intestinal parasitism was
      high, as well as the risk factors associated with this. Association with studied
      factors was evidenced.

PMID- 24892567
TI  - [Effect of exercise on high density lipoprotein subpopulations and blood
      pressure].
AB  - OBJECTIVE: Determine the relationship of exercise with serum levels of apoA-I and
      HDL2 and HDL3, subpopulations in hypertensive individuals from the city of
      Armenia - Quindio. METHODS: The interventions were two months of exercise. Blood
      pressure was taken with the recommendations of the Ministry of Health of
      Colombia. HDL subpopulations were measured with the method of precipitate ionic
      and the apoA-I was measured using nephelometry of Bindig site. RESULTS:
      Descriptive and inferential statistics were used for data analysis. A total of
      160 patients of whom 125 remained until the end of the project were gathered,
      that is, there was a 78.12 % retention, 28 % did the exercise. The analysis
      showed a highly significant reduction of systolic and diastolic blood pressure,
      higher in people who did exercise. The HDL were below normal before exercise,
      significantly increased with exercise but still remained below the reference
      values, the HDL2 increased significantly, while HDL3 decreased with normal levels
      of apoA-I. CONCLUSION: This study shows that exercise increases the total HDL,
      but the most important is that exercise modified the HDL subpopulations in a
      relationship that favors those which seem to have ateroprotective properties. The
      evidence of the interrelationship between protective factors provides new
      arguments for public health actions against the cardiovascular risk and
      hypertension.

PMID- 24892568
TI  - [Prevalence of occupational accidents and related factors in students of
      dentistry].
AB  - OBJECTIVE: Describe the prevalence of occupational accidents students of
      dentistry and associate it with factors of their clinical practice. METHODS:
      Cross-sectional study, developed in a public university in the city of Cartagena
      in 2010. Participants included 213 students in l pre-clinics and clinics practice
      of dentistry, selected by simple random sampling. A self-administered
      questionnaire was applied to evaluate the occurrence of accidents as well as the
      associated factors. The data were analyzed by prevalence rates with confidence
      intervals of 95 %, using the chi2 test, with significance levels of 0.05. The
      Association Strength was estimated by OR and the multivariate analysis through
      nominal logistic regression. RESULTS: The prevalence of occupational accidents is
      46 %, the type of accident most often is prick (48.7 %), caused mainly by the
      Explorer (28.9 %). 58.1 % of the accidents are reported and continue care
      protocol. 87.7 % of the students enfold the needle after use. At bivariate level,
      only statistically significant association between occupational accidents and
      semester was presented, being more frequent for the more advanced semesters
      (p=0.004). CONCLUSIONS: because of high prevalence of occupational accidents, it
      is necessary to insist on the implementation of strategies for safe and
      appropriate environments for the development of educational practices for
      students.

PMID- 24892569
TI  - [Marijuana consumption in students of a Colombian university].
AB  - OBJECTIVE: Describe pattern of behavior associated with the consumption of
      marijuana in students of the University of Tolima, Colombia, identifying their
      sociodemographic characteristics, knowledge, frequency of consumption, attitudes,
      practices and assessments of health effects resulting from consumption. METHODS:
      Transverse Descriptive study realized in the University of Tolima in 2009. The
      sample was of 700 students aged between 15 and 25 years, belonging to the
      different faculties. The survey was adapted from the National School of
      Addictions of the National Institute of Epidemiology of Mexico, (2002) and it
      underwent to tests of construct validity , reliability and analysis of internal
      consistency (sends inland), with Cronbach's alfa, with value of 0.79. RESULTS:
      The age of highest consumption focuses on the 18 to 21 age group, Men belonging
      to strata the 2 and 3 show the higher consumption. Those who live with one or
      both parents consume more than those who live alone or with friends. The
      consumptions are significant in programs as Topography, Architecture, Physical
      Education, Nursing and Medicine. CONCLUSIONS: In spite of knowing the harmful
      effects to health, its influence in negative changes of attitude and poor
      academic results, the consumption of marijuana prevails in the University of
      Tolima, motivated, among others, for the easy acquisition of marijuana inside the
      campus. The higher poverty increases consumption. The type of information
      provided and the source are vital at the time of formulating prevention
      strategies.

PMID- 24892570
TI  - [Public health stewardship and governance regarding the Colombian healthcare
      system, 2012-2013].
AB  - OBJECTIVE: Analysing decision-making concerning public health issues regarding
      the Colombian healthcare system from a market economy-based approach. METHODS:
      This study involved applying Glaser and Strauss's grounded theory in six
      Colombian cities during 2012: Bogota, Barranquilla, Bucaramanga, Leticia,
      Medellin and Pasto. 120 individual interviews were conducted with professionals
      involved in decision-making, running public healthcare programmes and making
      policy within public and private institutions. Fourteen focus groups were held
      with community organisation leaders. RESULTS: The findings suggested national and
      municipal health authorities' weak stewardship and ineffective governance
      regarding public healthcare policy and programmes, related to a lack of staff
      trained in public health management issues. In turn, this was related to
      political parties' interference and private insurers' particular interests and
      the structural fragmentation of functions and actors within the health system,
      thereby limiting public health development. CONCLUSIONS: A new axiology is
      necessary for achieving effective governance (I.e. cooperation between Colombian
      Healthcare Social Security System actors) to overcome current incompetence and
      financial self-interest predominating within the Colombian healthcare system.

PMID- 24892571
TI  - [Environmental health: the evolution of Colombia's current regulatory framework].
AB  - This essay presents an analysis of the evolution of environmental health
      management in Colombia, covering the period from the introduction of the
      Colombian Healthcare Code (1979) to laws 99 and 100 in 1993 and the introduction
      of Environmental Health Policy in Bogota DC (2011). It proposes a conceptual
      model for environmental health management at three levels: proximal (physical,
      chemical and biological setting), intermediate (natural and cultural environment)
      and distal (economic, political and social structures). Relevant aspects of
      environmental health policy in Bogota are analysed based on the proposed model. 

PMID- 24892572
TI  - [PM10 exposure-related respiratory symptoms and disease in children living in and
      near five coal-mining areas in the Cesar department of Colombia].
AB  - OBJECTIVES: Establishing the prevalence of respiratory symptoms and disease in
      children aged less than 12 years-old living within the Cesar department's coal
      mining area and possible associated factors. METHODS: This was a cross-sectional
      study of 1,627 children aged less than 10 years-old living in and near coal
      mining areas in the Cesar department who were exposed to different levels of PM10
      from 2008-2010; their PM10 exposure-related symptoms and respiratory diseases
      were measured, seeking an association with living in areas exposed to particulate
      material. RESULTS: Children living in areas close to coal-mining activity which
      also had high traffic volume had a higher rate of probable cases of asthma; those
      living in areas with traffic (not no coal-mining) were absent from school for
      more days due to acute respiratory disease. Respiratory symptoms were most
      commonly found in children experiencing living conditions which exposed them to
      cigarette or firewood smoke indoors, living in houses made with wattle and daub
      or adobe walls, living where animals were kept, living in damp housing and diesel
      powered dump trucks operating within 100 m or less of their housing. Living in
      areas having high traffic volume increased the risk of respiratory symptoms,
      acute respiratory disease and being absent from school. DISCUSSION: All the
      effects studied were associated with intramural conditions, individual factors or
      those associated with the immediate surroundings thereby coinciding with results
      found in similar studies regarding air pollution and health. It is thus suggested
      that regional strategies and policy be created for controlling and monitoring the
      air quality and health of people living in the Cesar department.

PMID- 24892573
TI  - [Indoor air pollution in extremely poor Colombian households].
AB  - OBJECTIVE: Characterising exposure to indoor air pollution arising from solid
      fuel use in extremely poor Colombian households. METHODS: Data from the September
      2012 survey by Red Unidos (literally United Network, the Colombian government's
      official instrument for identifying extremely poor households: n=1.3 million
      households and >5 million people) was used for two logistic regression models:
      factors associated with solid fuel used in cooking within households and an
      association between exposure to solid fuel use in households and the prevalence
      of limitations regarding individual health. RESULTS: According to the Red Unidos
      data-based models, 2.1 million people living in 530,000 extremely poor households
      were exposed to environmental health risk (i.e. household air pollution caused by
      solid fuel use). Such risk was found to be related to living in rural areas (odds
      ratio (OR)=19.4 95 % confidence interval (95 %CI): 19.2-19.6 %), having an Indian
      background (OR=2.9: 2.9-3.0 95 %CI) and, inversely (i.e. when living in towns),
      internal displacement (OR=0.6: 0.6-0.695 %CI). The prevalence of permanent
      cardiovascular and respiratory limitations and limited vision were associated
      with exposure to indoor air pollution arising from solid fuel use. DISCUSSION:
      Initiatives for improving environmental health and the quality of life for
      extremely poor rural households in Colombia must make full use of the available
      characterisation data and its impact for prioritising programmes aimed at
      reducing exposure to solid fuel use.

PMID- 24892574
TI  - [Estimating air quality change-associated health benefits by reducing PM10 in
      Bogota].
AB  - OBJECTIVE: The health and economic benefits associated with the reduction of the
      annual average concentration of particulate matter PM10 to 50 MUg/m(3) between
      2010 and 2020 were estimated and disaggregated in Zonal Planning Units in Bogota.
      MATERIALS AND METHODS: BenMap(r) was used for determining attributable cases and
      their economic valuation year per year, and the results were represented
      spatially for every borough and zonal planning unit of the city. The study used
      concentration-response functions to determine the mortality cases attributable to
      PM10 pollution and hospitalizations related with respiratory and cardiovascular
      diseases. RESULTS: 21,000 deaths associated with long-term exposure could be
      prevented for people over 30 years old and 900 deaths associated with long-term
      exposure for children under one year old. For children under five years old, more
      than 12,000 preventable hospitalizations for respiratory diseases, about 3,800
      emergency room visits, over 34,000 Acute Respiratory Diseases (ARD) cases and
      nearly 2,500 intensive care unit visits. For people over 5 years old, about 44000
      hospitalizations for respiratory diseases, 350 hospitalizations for
      cardiovascular diseases (people over 65 years old), and nearly 155,000 emergency
      room visits would be prevented. CONCLUSION: Economic benefits for 180 billion
      Colombian Pesos (95 million U.S. dollars) would be obtained and a benefit higher
      than 21 trillion Colombian pesos (11 billion U.S. dollars) in ten years,
      preventing attributable deaths.

PMID- 24892575
TI  - [PM10 environmental pollution in and around housing and respiratory capacity in
      Puerto Nare, Colombia].
AB  - OBJECTIVE: Exploring the relationship between PM10 intra- and extra-domiciliary
      levels and the lung function of people living in La Sierra, Antioquia, Colombia.
      MATERIALS AND METHODS: A survey and field observations were used for determining
      the environmental conditions and the immediate household environment of 124
      people who had taken a spirometric test. Meteorological conditions were
      monitored: temperature, relative humidity, rainfall, wind speed and PM10 (24
      hours) within and outside the houses. RESULTS: Indoor PM10 (0.05 mg/m3) in 50 %
      of the houses was <outdoor PM10 (0.06 mg/m3); there was 79.08 % relative
      humidity, 33.03 mm rainfall, 28.75 degrees C and 0.91 m/s wind speed. 25% of
      forced expiratory volumeA in 1 second (FEV1) was<74 %. There was a positive
      correlationbetween indoor and outdoor PM10 (0.197: p=0.029) and a negative
      correlation between indoor PM10 and wind speed (-0.215: p=0,017). A weak positive
      relationship was found between FEV1 and indoor and outdoor PM10. DISCUSSION: The
      results suggested that indoor pollution came from automobile emission, industrial
      combustionand unpaved roads (i.e. producing a lot of dust). PM10 decreased with
      increasing rain fall, higher relative humidity and increased wind speed.

PMID- 24892576
TI  - [The auditory and neuropsychological effects of school children's exposure to
      environmental noise in a locality in Bogota, 2010].
AB  - OBJECTIVE: Evaluating the effect of environmental noise on the auditory health of
      a group of students from a locality in Bogota, their educational development and
      leisure activities and the appearance of neuropsychological symptoms. METHODS:
      This was an observational cross-sectional prevalence study in a sample of 581, 10
      17 year-old children and adolescents in two district educational institutions,
      defined as higher (>65 dB) and lower exposure (<65 dB) according to an
      environmental noise map of the locality, such ranking being subsequently
      verified. A survey was made regarding their health-related background, perception
      of being exposed to noise and auditory health-related habits; a liminal tone
      audiometry of the airway was taken using the criteria recommended in the
      Infrastructure Technical Advisory Group'snoise-induced hearing loss (ITAG-NIHL)
      guidelines. RESULTS: The more exposed school exceeded the regulations concerning
      comfortable environmental noise levels (7/8 measurements). Both institutions'
      levels exceeded WHO recommendations (15/16 measurements); 14.8 % of students had
      some degree of hearing loss. No significant differences were identified regarding
      exposure; however, higher thresholds were found in the more exposed group when
      comparing mean hearing threshold. Students attending morning sessions had a
      greater prevalence of hearing loss and neuropsychological symptoms and neuro
      otological symptoms and difficulty in sleeping was reported amongst the more
      exposed students. CONCLUSION: A difference was found between students' hearing
      thresholds, depending on their exposure, suggesting an association with the
      levels of noise to which they are exposed.

PMID- 24892577
TI  - [International classification of functioning, disability and disability
      certification in Colombia].
AB  - Certifying disability in Colombia has been demanded by disabled people; the
      country has assumed such challenge within the frame work of current legislation
      and international agreements signed by Colombia. A model of international
      classification of functioning (ICF), disability and healthwas thus adopted as it
      has been validated internationally in several studies; it incorporates
      international standards thereby allowing reliable evaluation of individuals'
      functional status. This essayinitially defines the concept of disabilityand
      locates it within a historical context leading to current ICF domain structure
      and categories. Such instrument provides a common, wide-ranging framework for
      providing suitable allocation of services and general and specific benefits,
      while assessing the differential between disabled people's current performance
      and their potential. 

PMID- 24892578
TI  - The performance of students with and without disability on the 11th grade
      university admission test.
AB  - OBJECTIVE: Comparing standardized university admission scores between students
      with and without disability within the same school and also comparing the
      performance of students with hearing, visual and physical disability. METHODS:
      This was a retrospective cohort study which compared the test results of students
      with and without disabilities within the same school. A matched case-control
      study nested in a cohort was assembled. Standardized differences were calculated
      for comparing such scores. RESULTS: Students without disabilities performed
      significantly better than disabled ones(i.e. disabled students scored lower than
      their classmates). CONCLUSION: Further research is needed to determine whether
      the Colombian educational system, adjustments made to tests for this population
      or students' individual skills were the factors underlying the difference
      regarding the test results.

PMID- 24892579
TI  - [Disability certification as a tool for gaining access to human rights and social
      participation].
AB  - Given that one of the main reasons prioritising public policy agendas is related
      to implementing action responding to the increase in the prevalence of disability
      and the violation people of such people's rights, governments in many parts of
      the world have advanced disability certification as a tool for claiming rights,
      seeking to comply with the principles of dignity, liberty, equality and non
      discrimination regarding this population. Certification of disability In Colombia
      is novel and has been introduced to meet the provisions of national and
      international standards regarding handicapped people's rights. A first approach
      has thus been made through developing a disability certification manual aimed at
      healthcare institutions and professionals forming interdisciplinary teams; it was
      developed by assessing disabled people voluntarily undergoing certification and
      thus becoming a tool for claiming rights, facilitating access to services and
      benefits in terms of equity and social inclusion. 

PMID- 24892580
TI  - Bartonella clarridgeiae and Bartonella vinsonii subsp. berkhoffii exposure in
      captive wild canids in Brazil.
AB  - SUMMARY Wild canids are potential hosts for numerous species of Bartonella, yet
      little research has been done to quantify their infection rates in South America.
      We sought to investigate Bartonella seroprevalence in captive wild canids from 19
      zoos in Sao Paulo and Mato Grosso states, Brazil. Blood samples were collected
      from 97 wild canids belonging to four different native species and three European
      wolves (Canis lupus). Indirect immunofluorescent antibody testing was performed
      to detect the presence of B. henselae, B. vinsonii subsp. berkhoffii, B.
      clarridgeiae, and B. rochalimae. Overall, Bartonella antibodies were detected in
      11 of the canids, including five (12.8%) of 39 crab-eating foxes (Cerdocyon
      thous), three (11.1%) of 27 bush dogs (Speothos venaticus), two (8.7%) of 23
      maned wolves (Chrysocyon brachyurus) and one (12.5%) of eight hoary foxes
      (Lycalopex vetulus), with titres ranging from 1:64 to 1:512. Knowing that many
      species of canids make excellent reservoir hosts for Bartonella, and that there
      is zoonotic potential for all Bartonella spp. tested for, it will be important to
      conduct further research in non-captive wild canids to gain an accurate
      understanding of Bartonella infection in free-ranging wild canids in South
      America. 

PMID- 24892581
TI  - Ecological theory as a foundation to control pathogenic invasion in aquaculture.
AB  - Detrimental host-pathogen interactions are a normal phenomenon in aquaculture
      animal production, and have been counteracted by prophylactic use of antibiotics.
      Especially, the youngest life stages of cultivated aquatic animals are
      susceptible to pathogen invasion, resulting in disease and mortality. To
      establish a more sustainable aquatic food production, there is a need for new
      microbial management strategies that focus on 'join them' and not the traditional
      'beat them' approaches. We argue that ecological theory could serve as a
      foundation for developing sustainable microbial management methods that prevent
      pathogenic disease in larviculture. Management of the water microbiota in
      aquaculture systems according to ecological selection principles has been shown
      to decrease opportunistic pathogen pressure and to result in an improved
      performance of the cultured animals. We hypothesize that manipulation of the
      biodiversity of the gut microbiota can increase the host's resistance against
      pathogenic invasion and infection. However, substantial barriers need to be
      overcome before active management of the intestinal microbiota can effectively be
      applied in larviculture.

PMID- 24892584
TI  - Non-ambient crystallography - is extreme becoming common?

PMID- 24892583
TI  - Paging "Dr. Google": does technology fill the gap created by the prenatal care
      visit structure? Qualitative focus group study with pregnant women.
AB  - BACKGROUND: The prenatal care visit structure has changed little over the past
      century despite the rapid evolution of technology including Internet and mobile
      phones. Little is known about how pregnant women engage with technologies and the
      interface between these tools and medical care, especially for women of lower
      socioeconomic status. OBJECTIVE: We sought to understand how women use technology
      during pregnancy through a qualitative study with women enrolled in the Women,
      Infants, and Children (WIC) program. METHODS: We recruited pregnant women ages 18
      and older who owned a smartphone, at a WIC clinic in central Pennsylvania. The
      focus group guide included questions about women's current pregnancy, their
      sources of information, and whether they used technology for pregnancy-related
      information. Sessions were audiotaped and transcribed. Three members of the
      research team independently analyzed each transcript, using a thematic analysis
      approach. Themes related to the topics discussed were identified, for which there
      was full agreement. RESULTS: Four focus groups were conducted with a total of 17
      women. Three major themes emerged as follows. First, the prenatal visit structure
      is not patient-centered, with the first visit perceived as occurring too late and
      with too few visits early in pregnancy when women have the most questions for
      their prenatal care providers. Unfortunately, the educational materials women
      received during prenatal care were viewed as unhelpful. Second, women turn to
      technology (eg, Google, smartphone applications) to fill their knowledge gaps.
      Turning to technology was viewed to be a generational approach. Finally, women
      reported that technology, although frequently used, has limitations. CONCLUSIONS:
      The results of this qualitative research suggest that the current prenatal care
      visit structure is not patient-centered in that it does not allow women to seek
      advice when they want it most. A generational shift seems to have occurred,
      resulting in pregnant women in our study turning to the Internet and smartphones
      to fill this gap, which requires significant skills to navigate for useful
      information. Future steps may include developing interventions to help health
      care providers assist patients early in pregnancy to seek the information they
      want and to become better consumers of Internet-based pregnancy resources.

PMID- 24892585
TI  - A simple approach to understand the high-pressure calcium conundrum.

PMID- 24892582
TI  - Phylogenetic analysis of HIV type 1 CRF02_AG in multiple genes in Italian and
      African patients living in Italy.
AB  - Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF)
      02_AG is a major recombinant variant in different geographic areas and is
      predominant in West and Central Africa. Of particular interest is the increased
      frequency of CRF02_AG in patients living in Italy. In the present study,
      phylogenetic analyses were performed on gag, pol (integrase), and env (gp120 and
      gp41) gene sequences from 34 CRF02_AG-infected patients living in Italy. Thirty
      out of 34 (89.4%) patients were from western Africa, 3/34 (8.8%) were born in
      Italy, and 1/34 (2.9%) was from Cuba. Phylogenetic analysis revealed the presence
      of a well-supported clade (aLRT score>0.75) of sequences only in gp120 and gp41
      trees. Evolutionary rate estimation showed a faster evolution for the gp120 gene
      with respect to the gag, integrase, and gp41 genes. This finding was confirmed by
      the analysis of interpatient variability. Intrapatient variability was greater in
      gp120 gene sequences; 10/19 (52.6%; p<0.001) patients had a ratio of dN/dS>1 as
      compared with gag, integrase, and gp41 gene sequences with dN/dS ratios<1. In
      summary, phylogenetic analyses of CRF02_AG strains offer a perspective on
      intrapatient and interpatient variability among CRF02_AG-infected patients living
      in Italy. In addition, divergent phylogenetic relationships were observed among
      different genomic regions.

PMID- 24892586
TI  - Crystallographic studies of gas sorption in metal-organic frameworks.

PMID- 24892588
TI  - Structural simplicity and complexity of compressed calcium: electronic origin.
AB  - A simple cubic structure with one atom in the unit cell found in compressed
      calcium is counterintuitive to the traditional view of a tendency towards densely
      packed structures with an increase in pressure. To understand this unusual
      transformation it is necessary to assume electron transfer from the outer core
      band to the valence band, and an increase of valence electron number for calcium
      from 2 to ~ 3.5. This assumption is supported by the Fermi sphere-Brillouin zone
      interaction model that increases under compression. The recently found structure
      of Ca-VII with a tetragonal cell containing 32 atoms (tI32) is similar to that in
      the intermetallic compound In5Bi3 with 3.75 valence electrons per atom.
      Structural relations are analyzed in terms of electronic structure resemblance.
      Correlations of structure and physical properties of Ca are discussed. 

PMID- 24892589
TI  - Structures of the elements - crystallography and art.
AB  - Since simple data tables on phase transitions and structural systematics of the
      elements over a wide range of pressure and temperature are difficult to
      comprehend, this paper illustrates these systematics with some artwork together
      with an artist's view of the equations of states for the elements. 

PMID- 24892590
TI  - Temperature- and pressure-dependent structural study of {Fe(pmd)2[Ag(CN)2]2}n
      spin-crossover compound by neutron Laue diffraction.
AB  - The effect of pressure (up to 0.17 GPa) on the spin-crossover compound
      {Fe(pmd)2[Ag(CN)2]2}n [orthorhombic isomer (II), pmd = pyrimidine] has been
      investigated by temperature- and pressure-dependent neutron Laue diffraction and
      magnetometry. The cooperative high-spin <-> low-spin transition, centred at ca
      180 K at ambient pressure, is shifted to higher temperatures as pressure is
      applied, showing a moderate sensitivity of the compound to pressure, since the
      spin transition is displaced by ca 140 K GPa(-1). The space-group symmetry
      (orthorhombic Pccn) remains unchanged over the pressure-temperature (P-T) range
      studied. The main structural consequence of the high-spin to low-spin transition
      is the contraction of the distorted octahedral [FeN6] chromophores, being more
      marked in the axial positions (occupied by the pmd units), than in the equatorial
      positions (occupied by four [Ag(CN)2](-) bridging ligands). 

PMID- 24892591
TI  - High-pressure-induced structural changes, amorphization and molecule penetration
      in MFI microporous materials: a review.
AB  - This is a comparative study on the high-pressure behavior of microporous
      materials with an MFI framework type (i.e. natural mutinaite, ZSM-5 and the all
      silica phase silicalite-1), based on in-situ experiments in which penetrating and
      non-penetrating pressure-transmitting media were used. Different pressure-induced
      phenomena and deformation mechanisms (e.g. pressure-induced over-hydration,
      pressure-induced amorphization) are discussed. The influence of framework and
      extra-framework composition and of the presence of silanol defects on the
      response to the high pressure of MFI-type zeolites is discussed. 

PMID- 24892587
TI  - Crystallographic studies of gas sorption in metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) are a class of porous crystalline materials of
      modular design. One of the primary applications of these materials is in the
      adsorption and separation of gases, with potential benefits to the energy,
      transport and medical sectors. In situ crystallography of MOFs under gas
      atmospheres has enabled the behaviour of the frameworks under gas loading to be
      investigated and has established the precise location of adsorbed gas molecules
      in a significant number of MOFs. This article reviews progress in such
      crystallographic studies, which has taken place over the past decade, but has its
      origins in earlier studies of zeolites, clathrates etc. The review considers
      studies by single-crystal or powder diffraction using either X-rays or neutrons.
      Features of MOFs that strongly affect gas sorption behaviour are discussed in the
      context of in situ crystallographic studies, specifically framework flexibility,
      and the presence of (organic) functional groups and unsaturated (open) metal
      sites within pores that can form specific interactions with gas molecules. 

PMID- 24892592
TI  - High-pressure phase transitions in the rare-earth orthoferrite LaFeO3.
AB  - Sequential Rietveld refinements were applied on high-pressure synchrotron powder
      X-ray diffraction measurements of lanthanum ferrite (LaFeO3) revealing two phase
      transitions on the room-temperature isotherm up to a pressure of 48 GPa. The
      first structural phase transition of second order occurs at a pressure of 21.1
      GPa, changing the space group from Pbnm to Ibmm. The second transition, involving
      a isostructural first-order phase transition, occurs at approximately 38 GPa,
      indicating a high-spin to low-spin transition of the Fe(3+) ion. Following the
      behavior of the volume up to the hydrostatic limit of methanol-ethanol it was
      possible to use inverted equations of state (EoS) to determine a bulk modulus of
      B0 = 172 GPa and a corresponding pressure derivative of B'0 = 4.3. In addition,
      the linearized version of the inverted EoS were used to determine the
      corresponding moduli and pressure derivatives for each lattice direction. 

PMID- 24892593
TI  - High-pressure study of binary thorium compounds from first principles theory and
      comparisons with experiment.
AB  - The high-pressure structural behaviour of a series of binary thorium compounds
      ThX (X = C, N, P, As, Sb, Bi, S, Se, Te) is studied using the all-electron full
      potential linear muffin-tin orbital (FP-LMTO) method within the generalized
      gradient approximation (GGA) for the exchange and correlation potential. The
      calculated equlibrium lattice parameters and bulk moduli, as well as the
      equations of state agree well with experimental results. New experiments are
      reported for ThBi and ThN. Calculations are performed for the ThX compounds in
      the NaCl- and CsCl-type crystal structures, and structural phase transitions from
      NaCl to CsCl are found in ThP, ThAs, ThSb and ThSe at pressures of 26.1, 22.1,
      8.1 and 23.2 GPa, respectively, in excellent agreement with experimental results.
      ThC, ThN and ThS are found to be stable in the NaCl structure, and ThBi and ThTe
      in the CsCl structure, for pressures below 50 GPa. The electronic structures of
      the ThX compounds are studied using the quasiparticle self-consistent GW method
      (G: Green function, W: dynamically screened interaction). 

PMID- 24892594
TI  - High-pressure studies of palladium and platinum thioether macrocyclic dihalide
      complexes.
AB  - The mononuclear macrocyclic Pd(II) complex cis-[PdCl2([9]aneS3)] ([9]aneS3 =
      1,4,7-trithiacyclo-nonane) converts at 44 kbar into an intensely coloured chain
      polymer exhibiting distorted octahedral coordination at the metal centre and an
      unprecedented [1233] conformation for the thioether ligand. The evolution of an
      intramolecular axial sulfur-metal interaction and an intermolecular equatorial
      sulfur-metal interaction is central to these changes. High-pressure
      crystallographic experiments have also been undertaken on the related complexes
      [PtCl2([9]aneS3)], [PdBr2([9]aneS3)], [PtBr2([9]aneS3)], [PdI2([9]aneS3)] and
      [PtI2([9]aneS3)] in order to establish the effects of changing the halide ligands
      and the metal centre on the behaviour of these complexes under pressure. While
      all complexes undergo contraction of the various interaction distances with
      increasing pressure, only [PdCl2([9]aneS3)] undergoes a phase change. Pressure
      induced I...I interactions were observed for [PdI2([9]aneS3)] and
      [PtI2([9]aneS3)] at 19 kbar, but the corresponding Br...Br interactions in
      [PdBr2([9]aneS3)] and [PtBr2([9]aneS3)] only become significant at much higher
      pressure (58 kbar). Accompanying density functional theory (DFT) calculations
      have yielded interaction energies and bond orders for the sulfur-metal
      interactions. 

PMID- 24892595
TI  - Isothermal and isochoric crystallization of highly hygroscopic pyridine N-oxide
      of aqueous solution.
AB  - Highly hygroscopic pyridine N-oxide, C5H5NO, dissolves in water absorbed from
      atmospheric air, but it crystallizes in the neat form of the aqueous solution
      under high pressure. The crystals grown at high-pressure isochoric conditions are
      of the same phase as that obtained from anhydrous crystallization at ambient
      pressure. This feature can be employed for retrieving compounds highly soluble in
      water from their aqueous solutions. The crystal structure is strongly stabilized
      by CH...O contacts. The crystal compression and thermal expansion as well as
      three shortest H...O distances comply with the inverse-relationship rule of
      pressure and temperature changes. 

PMID- 24892596
TI  - Structure-melting relations in isomeric dibromobenzenes.
AB  - 1,4-Dibromobenzene melts at a considerably higher temperature than the 1,2- and
      1,3-isomers. This melting-point difference is consistent with the molecular
      symmetry, as described by Carnelley's rule, and with the frequency of Br...Br
      halogen bonds. The lowest melting point of 1,3-dibromobenzene correlates with its
      two symmetry-independent molecules, indicating their inability to pack closely.
      Single crystals of 1,2- and 1,3-dibromobenzene have been grown under isochoric
      conditions in a diamond-anvil cell and at isobaric conditions in a glass
      capillary. Their structures have been determined in situ by X-ray diffraction. At
      295 K 1,2-dibromobenzene crystallizes at 0.2 GPa as orthorhombic, space group
      Pbca, Z' = 1, and 1,3-dibromobenzene at 0.3 GPa as orthorhombic, space group
      P212121, Z' = 2. The same crystal phases are formed at ambient pressure by
      freezing these liquids below 256.15 and 248.45 K, respectively. The third isomer,
      1,4-dibromobenzene, is a solid at room temperature and crystallizes as
      monoclinic, space group P21/a. Striking relations between the structures and
      melting points of the corresponding dibromobenzene and dichlorobenzene isomers
      have been discussed. 

PMID- 24892597
TI  - In-situ X-ray diffraction activation study on an Fe/TiO2 pre-catalyst.
AB  - This study focuses on the use of in situ powder X-ray diffraction (PXRD) and
      quantitative phase analysis using the Rietveld method to monitor the structural
      properties of a titania-supported iron (10% Fe/TiO2) pre-catalyst during
      calcination (oxidation) and activation (reduction) in the temperature range 25
      900 degrees C. The TiO2 oxidation study revealed an increase in anatase particle
      size before the anatase to rutile phase transformation, lending credibility to
      the bridging mechanism proposed by Kim et al. [(2007), Mater. Sci. Forum, 534
      536, 65-68]. Pre-catalyst oxidation experiments allowed for the determination of
      a suitable calcination temperature (450 degrees C) of the pre-catalyst in terms
      of maximum hematite concentration and appropriate particle size. These
      experiments also confirmed that the anatase to rutile phase transformation
      occurred at higher temperatures after Fe addition and that anatase was the sole
      donor of Ti(4+) ions, which are known to migrate into hematite (Gennari et al.,
      1998), during the formation of pseudobrookite (Fe2TiO5) at temperatures above 690
      degrees C. Using the results from the oxidation experiments, two pre-catalyst
      samples were calcined at different temperatures; one to represent the preferred
      case and one to represent a case where the pre-catalyst had been excessively
      heated. Samples of the excessively heated catalysts were exposed to different
      reducing gas atmospheres (5, 10 and 100% H2/N2) and heated in the in situ PXRD
      reactor, so that diffraction data could be collected during the activation
      process. The results show that reduction with gases containing low concentrations
      of H2 (5 and 10%) led to the formation of ilmenite (FeTiO3) and we were able to
      show that both anatase and rutile are consumed in the reaction. Higher
      concentrations of H2 led to the formation of magnetite (Fe3O4) and metallic iron
      (Fe(0)). We also noted a decrease in the anatase to rutile transformation
      temperature under reducing atmospheres when compared with the pre-catalyst heat
      treatment experiment. A reduced calcination temperature prior to reduction
      allowed more facile Fe reduction. 

PMID- 24892598
TI  - In-situ high-pressure powder X-ray diffraction study of alpha-zirconium
      phosphate.
AB  - The high-pressure structural chemistry of alpha-zirconium phosphate, alpha
      Zr(HPO4)2.H2O, was studied using in-situ high-pressure diffraction and
      synchrotron radiation. The layered phosphate was studied under both hydrostatic
      and non-hydrostatic conditions and Rietveld refinement carried out on the
      resulting diffraction patterns. It was found that under hydrostatic conditions no
      uptake of additional water molecules from the pressure-transmitting medium
      occurred, contrary to what had previously been observed with some zeolite
      materials and a layered titanium phosphate. Under hydrostatic conditions the
      sample remained crystalline up to 10 GPa, but under non-hydrostatic conditions
      the sample amorphized between 7.3 and 9.5 GPa. The calculated bulk modulus, K0 =
      15.2 GPa, showed the material to be very compressible with the weak linkages in
      the structure of the type Zr-O-P. 

PMID- 24892599
TI  - Effect of pressure on methylated glycine derivatives: relative roles of hydrogen
      bonds and steric repulsion of methyl groups.
AB  - Infinite head-to-tail chains of zwitterions present in the crystals of all amino
      acids are known to be preserved even after structural phase transitions. In order
      to understand the role of the N-H...O hydrogen bonds linking zwitterions in these
      chains in structural rearrangements, the crystal structures of the N-methyl
      derivatives of glycine (N-methylglycine, or sarcosine, with two donors for
      hydrogen bonding; two polymorphs of N,N-dimethylglycine, DMG-I and DMG-II, with
      one donor for hydrogen bond; and N,N,N-trimethylglycine, or betaine, with no
      hydrogen bonds) were studied at different pressures. Methylation has not only
      excluded the formation of selected hydrogen bonds, but also introduced bulky
      mobile fragments into the structure. The effects of pressure on the systems of
      the series were compared with respect to distorting and switching over hydrogen
      bonds and inducing reorientation of the methylated fragments. Phase transitions
      with fragmentation of the single crystals into fine powder were observed for
      partially methylated N-methyl- and N,N-dimethylglycine, whereas the structural
      changes in betaine were continuous with some peculiar features in the 1.4-2.9 GPa
      pressure range and accompanied by splitting of the crystals into several large
      fragments. Structural rearrangements in sarcosine and betaine were strongly
      dependent on the rate of pressure variation: the higher the rate of increasing
      pressure, the lower the pressure at which the phase transition occurred. 

PMID- 24892600
TI  - A combined study of the equation of state of monazite-type lanthanum
      orthovanadate using in situ high-pressure diffraction and ab initio calculations.
AB  - Lanthanum orthovanadate (LaVO4) is the only stable monazite-type rare-earth
      orthovanadate. In the present paper the equation of state of LaVO4 is studied
      using in situ high-pressure powder diffraction at room temperature, and ab initio
      calculations within the framework of the density functional theory. The
      parameters of a second-order Birch-Murnaghan equation of state, i.e. those fitted
      to the experimental and theoretical data, are found to be in perfect agreement -
      in particular, the bulk moduli are almost identical, with values of 106 (1) and
      105.8 (5) GPa, respectively. In agreement with recent reported experimental data,
      the compression is shown to be anisotropic. Its nature is comparable to that of
      some other monazite-type compounds. The softest compression direction is
      determined. 

PMID- 24892601
TI  - The alpha <-> beta phase transitions of Zn2P2O7 revisited: existence of an
      additional intermediate phase with an incommensurately modulated structure.
AB  - Zn2P2O7 crystallizes in a thortveitite-like structure and features temperature
      dependent polymorphism. At high temperatures (T > 500 K), the aristotype phase
      beta-Zn2P2O7 (C2/m, Z = 2, a ? 6.60, b ? 8.28, c ? 4.53 A, beta ? 105.4 degrees )
      is stable. At lower temperatures the lock-in phase alpha1-Zn2P2O7 [at 350 K:
      I2/c, Z = 12, a = 20.1131 (13), b = 8.2769 (6), c = 9.109 (3) A, beta = 106.338
      (16) degrees ], a sixfold superstructure with commensurate modulation vector q =
      (1/3, 0, 1/2), is stable. Between the stability ranges of the alpha1- and beta
      phases exists the intermediate, incommensurately modulated alpha2-Zn2P2O7 phase
      with modulation wavevector q ? (0.33, 0, 0.40) and C2/m(alpha, 0, gamma)0s
      superspace group symmetry. The alpha1 -> alpha2 lock-in phase transition at TL =
      408 K is of first-order and features virtually no hysteresis. It is immediately
      followed by the second-order alpha2 -> beta transition to the non-modulated phase
      at TI ? 430 K. This transformation is sluggish and even at T = 500 K very weak
      satellite reflections of the alpha2-phase were observed. Both phase transitions
      were analyzed with differential scanning calorimetry and high-temperature powder
      and single-crystal X-ray diffraction. The crystal structures of the alpha1- and
      alpha2-phases were refined from single crystal data collected at T = 350, 400,
      405, 410, 415, 420, 425, 430, 450 and 500 K. Different models describing the slow
      transition from the incommensurately modulated alpha2- to the non-modulated beta
      phase were tested. In the model resulting in the best residuals, the bridging O
      atom of the [P2O7] group, which is located on a 2/m position in the basic
      structure, is described as an overlap of an atom ordered in internal space and
      one atom disordered around the mirror plane. The occupancy of the ordered atom
      decreases with temperature until at T = 500 K virtually only the disordered atom
      remains. Simultaneously, the amplitude of the modulation functions of the
      remaining atoms decreases, so that the T = 500 K structure can be considered as
      the C2/m aristotype structure, although the diffraction pattern still features
      satellite reflections of first order with very low intensities. 

PMID- 24892603
TI  - Intermolecular interactions, charge-density distribution and the electrostatic
      properties of pyrazinamide anti-TB drug molecule: an experimental and theoretical
      charge-density study.
AB  - An experimental charge-density analysis of pyrazinamide (a first line
      antitubercular drug) was performed using high-resolution X-ray diffraction data
      [(sin theta/lambda)max = 1.1 A(-1)] measured at 100 (2) K. The structure was
      solved by direct methods using SHELXS97 and refined by SHELXL97. The total
      electron density of the pyrazinamide molecule was modeled using the Hansen
      Coppens multipole formalism implemented in the XD software. The topological
      properties of electron density determined from the experiment were compared with
      the theoretical results obtained from CRYSTAL09 at the B3LYP/6-31G** level of
      theory. The crystal structure was stabilized by N-H...N and N-H...O hydrogen
      bonds, in which the N3-H3B...N1 and N3-H3A...O1 interactions form two types of
      dimers in the crystal. Hirshfeld surface analysis was carried out to analyze the
      intermolecular interactions. The fingerprint plot reveals that the N...H and
      O...H hydrogen-bonding interactions contribute 26.1 and 18.4%, respectively, of
      the total Hirshfeld surface. The lattice energy of the molecule was calculated
      using density functional theory (B3LYP) methods with the 6-31G** basis set. The
      molecular electrostatic potential of the pyrazinamide molecule exhibits extended
      electronegative regions around O1, N1 and N2. The existence of a negative
      electrostatic potential (ESP) region just above the upper and lower surfaces of
      the pyrazine ring confirm the pi-electron cloud. 

PMID- 24892604
TI  - New ordered phase in the quasi-binary UAl3-USi3 system.
AB  - The industrial importance of the U-Al-Si system stems from the fact that during
      processing the Al-based alloy (containing Si as impurity), used for the cladding
      of U (fuel in nuclear reactors), undergoes heat treatment which stimulates
      diffusion between the fuel and the cladding. One of the possible ways to
      represent the ternary U-Al-Si phase diagram is the construction of an UAl3-USi3
      quasi-binary phase diagram. On the one hand, since the UAl3 and USi3 phases are
      isostructural, an isomorphous phase diagram is expected; on the other hand, some
      researchers observed a miscibility gap at lower temperatures. During our study of
      the UAl3-USi3 quasi-binary phase diagram, a new stable U(Alx,Si1 - x)3 phase was
      identified. The structure of this phase was determined, using a combination of
      electron crystallography and powder X-ray diffraction methods, as tetragonal
      [I4/mmm (No.139) space group], with lattice parameters a = b = 8.347 (1), c =
      16.808 (96) A. Its unit cell has 64 atoms and it can be described as an ordered
      variant of the U(Al,Si)3 solid solution. A Barnighausen tree was constructed
      using the original U(Al,Si)3 structure as an aristotype. 

PMID- 24892602
TI  - Understanding the structure details when drying hydrate crystals of
      pharmaceuticals - interpretations from diffuse scattering and inter-modulation
      satellites of a partially dehydrated crystal.
AB  - Simplified models for the crystal lattice of the sesquihydrate form of the hemi
      sulfate salt of (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H
      cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazol[4,5b]pyridin-1-yl)-1
      piperidine carboxylate (BMS-927711, C28H29F2N6O3(+)) are used to calculate
      diffuse diffraction features in order to develop a mechanistic understanding of
      the dehydration process with respect to disruption of the lattice, since a Bragg
      model cannot be established. The model demonstrates that what we observe when the
      water leaves the crystal is partial transformation from the parent form to a
      child form (a new form, less hydrated and structurally related to the parent).
      Yet this 'dried' structure is not a pure phase. It consists of semi-random layers
      of both child, parent and an interfacial layer which has a modulated structure
      that represents a transitory phase. Understanding the fact that a single 'dried'
      crystal can have the disordered layer structure described as well as
      understanding mechanistic relationships between the phases involved can have
      implications in understanding the effect of common large scale bulk drying
      procedures. During the development of BMS-927711, difficulties did arise during
      characterization of the dried bulk when using only routine solid-state analysis.
      The material is now better understood from this diffraction study. The
      diffraction experiments also reveal intermodulation satellites, which upon
      interpretation yield even more structural information about the crystal
      transformation. The model suggests the mechanism of transformation is laminar in
      which layers of the crystal are driven to approach a stable B-centered supercell
      phase of lower water content. 

PMID- 24892605
TI  - beta-Cyclodextrin dimethylformamide 12.5 hydrate: a deeper insight into beta
      cyclodextrin crystal packing.
AB  - The structure of a 1:1 beta-cyclodextrin-dimethylformamide hydrated complex has
      been determined from single-crystal X-ray diffraction data. A complete study of
      the structure is presented herein, including invariom refinement and interaction
      energy calculations. The structure has unit-cell parameters that are different
      from those of other beta-cyclodextrin complexes crystallizing in the same space
      group, but exhibits the known herringbone packing type. A structural comparison
      of these complexes has been carried out with XPac in order to understand the
      origin of the differences in packing and unit-cell parameters. The results show
      that the differences are most likely ascribed to variations in hydration and in
      the hydrogen-bonded network. 

PMID- 24892606
TI  - Anisotropic thermal expansion in a metal-organic framework.
AB  - Ionothermal reaction between Mn(II)(acetate)2.4H2O and 1,3,5-benzenetricarboxylic
      acid (H3BTC) in either of the two ionic liquids 1-ethyl-3-methylimidazolium
      bromide (EMIMBr) and 1-ethyl-3-methylimidazolium tosylate (EMIMOTs) resulted in
      the formation of the new metal-organic framework (MOF) EMIM[Mn(II)BTC] (BTC =
      1,3,5-benzenetricarboxylate). The compound crystallizes in the orthorhombic space
      group Pbca with unit-cell parameters of a = 14.66658 (12), b = 12.39497 (9), c =
      16.63509 (14) A at 100 K. Multi-temperature single-crystal (15-340 K) and powder
      X-ray diffraction studies (100-400 K) reveal strongly anisotropic thermal
      expansion properties. The linear thermal expansion coefficients, alphaL(l),
      attain maximum values at 400 K along the a- and b-axis, with alphaL(a) = 115 *
      10(-6) K(-1) and alphaL(b) = 75 * 10(-6) K(-1). At 400 K a negative thermal
      expansion coefficient of -40 * 10(-6) K(-1) is observed along the c-axis. The
      thermal expansion is coupled to a continuous deformation of the framework, which
      causes the structure to expand in two directions. Due to the rigidity of the
      linker, the expansion in the ab plane causes the network to contract along the c
      axis. Hirshfeld surface analysis has been used to describe the interaction
      between the framework structure and the EMIM cation that resides within the
      channel. This reveals a number of rather weak interactions and one governing
      hydrogen-bonding interactions. 

PMID- 24892607
TI  - Linear alkaline earth metal phosphinate coordination polymers: synthesis and
      structural characterization.
AB  - Reaction of alkaline earth metal salts with diphenylphosphinic acid in
      dimethylformamide solvent afforded four coordination polymers:
      [Mg3(O2PPh2)6(DMF)2].2DMF (I), [Ca(O2PPh2)2(DMF)2] (II), [Sr(O2PPh2)2(DMF)2]
      (III) and [Ba(O2PPh2)2(DMF)2] (IV) (where DMF is N,N-dimethylformamide). Single
      crystal X-ray diffraction revealed that all four compounds produce linear chain
      structures in the solid state, with the Ca, Sr and Ba forming isostructural
      crystals. The bulk materials were characterized by FT-IR and (1)H NMR
      spectroscopy and elemental analyses. 

PMID- 24892608
TI  - Universal 'bond valence versus bond length' correlation curve for manganese
      oxygen bonds.
AB  - The oxidation-state independent 'bond valence (s) versus bond length (r)'
      correlation curve for manganese-oxygen bonds has been closely approximated using
      the modified two-parameter Tromel s = f(r) function [Tromel (1983). Acta Cryst.
      B39, 664-669], s = [(r0 - l)/(r - l)](2), where r0 = 1.763 (2) A and l = 1.148
      (9) A. The r0 and l refinable parameters of the above function can be regarded as
      the alternative bond-valence parameters intended for use in the modern bond
      valence model [Brown (2009). Chem. Rev. 109, 6858-6919] in cases where the
      traditional bond-valence parameters (r0; n) and (r0; b) fail. 

PMID- 24892609
TI  - Electronically driven structural transitions in A10(PO4)6F2 apatites (A = Ca, Sr,
      Pb, Cd and Hg).
AB  - It is shown that there is a dynamic lattice instability in the aristotype P63/m
      structure of A10(PO4)6F2 apatites containing divalent A-site Cd or Hg cations
      with (n - 1)d(10)ns(0) electronic configurations. The distortion to a low
      symmetry P?bar{1} triclinic structure is driven by an electronic mechanism rather
      than from ionic size mismatch. Our theoretical work provides key insights into
      the role of the electronic configurations of A cations in fluorapatites. 

PMID- 24892610
TI  - Beginning of the end of Onchocerciasis in the Americas.

PMID- 24892611
TI  - Women's expectations and evaluation of a maternal educational program.
AB  - OBJECTIVES: To identify the expectations of women requesting the maternal
      education program (ME) and to determine their evaluation of it. METHODS: a multi
      centric observational study was conducted in four hospitals in Spain in 2011 with
      primiparous women. Socio-demographic and obstetrical variables, among others,
      were collected through interviews and reviews of medical records. The analysis
      estimated crude and adjusted odds ratios using logistic regression with a
      confidence interval of 95%. RESULTS: Newborn care was most requested type of
      content desired by women (80.33%). Eleven and one quarter percent (11.25%) of the
      women evaluated ME as being of little or no usefulness or benefit. Women
      appreciated the follow-up care given during pregnancy and childbirth but ME was
      not noted as influencing the measurement of these processes (p> 0.05).
      CONCLUSIONS: Newborn care was the type of subject mainly demanded by the women in
      the ME program. Women evaluated ME as being a useful program.

PMID- 24892612
TI  - The effects of socioeconomic status and short stature on overweight, obesity and
      the risk of metabolic complications in adults.
AB  - OBJECTIVE: to observe the relationship between socioeconomic status, height and
      nutritional problems related to obesity, overweight and risk of metabolic
      complications in men and women of Medellin (Colombia). METHODS: cross-sectional
      study with a sample of 5556 adults between 18 and 69 years of age. We assessed
      weight, height and waist circumference. Socioeconomic variables were evaluated by
      family income, socioeconomic stratum and academic level achieved. RESULTS: we
      found that in men and women the height reached in adulthood is associated with
      socioeconomic conditions as measured by the socioeconomic strata and family
      income. In women, height, age, and socioeconomic strata are associated with
      obesity, overweight and risk of obesity, and risk of metabolic complications.
      CONCLUSION: These results are not only from individual unhealthy habits, such as
      eating patterns based on high density foods combined with low energy expenditure,
      but also from the cumulative effect of food deprivation throughout life.
      Therefore, policies intended to prevent them should take a preventive approach
      that begins before birth and continues during childhood and adulthood.

PMID- 24892613
TI  - Descriptive epidemiology of childhood cancer in Cali: Colombia 1977-2011.
AB  - AIM: The objective of the present report is to describe the occurrence and
      survival patterns of childhood cancer over the last 20 years in Cali. METHODS:
      Information was obtained from the Cancer Population Registry in Cali and the
      Municipal Department of Health . Childhood cancer international classification
      was used. The vital status was obtained from MDH death certificate and hospital
      databases. Additionally, clinical records were revised and, in some cases,
      telephone contact was carried out. Follow-up was done until 31/12/2011. Incident
      and mortality rates were estimated and adjusted for age. Life-tables were made to
      estimate overall survival. RESULTS: Between the years of 1977-2011, there were
      2311 cases identified in children under 15 years of age. The IR and MR for Cali
      were found to be 141.2 and 55.6 per million of people per year. Leukemias,
      lymphomas, CNS tumors and soft tissue sarcomas showed IR of 60.1, 20.5, 25.7 and
      9.4, respectively. 5-years OS was 48%, and showed an improvement from 24.9%+/-4.3
      to 51.8%+/-4.6, compared 1992-96 vs 2002-06 periods. CONCLUSION: The IR found is
      comparable with those described in affluent countries. Taking into account that
      pediatric cancer is curable for about 75-80% of the cases, it presents an
      enormous challenge to the Colombian health system: to improve current clinical
      results.

PMID- 24892614
TI  - Validity and reliability of the Short Physical Performance Battery (SPPB): a
      pilot study on mobility in the Colombian Andes.
AB  - OBJECTIVES: To assess the validity (convergent and construct) and reliability of
      the Short Physical Performance Battery (SPPB) among non-disabled adults between
      65 to 74 years of age residing in the Andes Mountains of Colombia. METHODS:
      Design Validation study; PARTICIPANTS: 150 subjects aged 65 to 74 years recruited
      from elderly associations (day-centers) in Manizales, Colombia. MEASUREMENTS: The
      SPPB tests of balance, including time to walk 4 meters and time required to stand
      from a chair 5 times were administered to all participants. Reliability was
      analyzed with a 7-day interval between assessments and use of repeated ANOVA
      testing. Construct validity was assessed using factor analysis and by testing the
      relationship between SPPB and depressive symptoms, cognitive function, and self
      rated health (SRH), while the concurrent validity was measured through
      relationships with mobility limitations and disability in Activities of Daily
      Living (ADL). ANOVA tests were used to establish these associations. RESULTS:
      Test-retest reliability of the SPPB was high: 0.87 (CI95%: 0.77-0.96). A one
      factor solution was found with three SPPB tests. SPPB was related to self-rated
      health, limitations in walking and climbing steps and to indicators of
      disability, as well as to cognitive function and depression. There was a graded
      decrease in the mean SPPB score with increasing disability and poor health.
      CONCLUSION: The Spanish version of SPPB is reliable and valid to assess physical
      performance among older adults from our region. Future studies should establish
      their clinical applications and explore usage in population studies.

PMID- 24892615
TI  - The Effects of Plasmodium vivax Gestational Malaria on the Clinical and Immune
      Status of Pregnant Women in Northwestern Colombia.
AB  - OBJECTIVE: The study explored the effects of Plasmodium vivax infection on the
      balance of pro- versus anti- inflammatory cytokines and chemokines and their
      relationship with some clinical and epidemiology outcomes. METHODS: Thirty-five
      pregnant women were recruited. Of these, 15 subjects had malaria at delivery
      (GM+), and 20 had no exposition to infection throughout the pregnancy (GM-) and
      at delivery. Epidemiological and clinical data were recorded after reviewing the
      clinical records. At delivery, whole blood from the mother as well as placental
      tissue was collected. Diagnosis of infection was performed by thick smear and a
      polymerase chain reaction (PCR). Expression of pro-inflammatory and anti
      inflammatory cytokines and chemokines was measured by a real time PCR. RESULTS:
      The clinical and epidemiological variables explored were similar in both groups,
      with the exception of gestational age. When comparing the GM+ group with the GM-
      group, it is clear that although the differences generally are not significant,
      pro- inflammatory cytokines are elevated in both maternal blood and placental;
      anti-inflammatory ones are elevated in the mother and reduced in the placenta,
      and the chemokines are reduced in both compartments, except for MCP-1 which is
      elevated in all. CONCLUSION: The results appear to be strongly affected by the
      small number of women with GM by P. vivax at childbirth. Additional studies are
      needed with larger groups in this and other regions of the country.

PMID- 24892616
TI  - Dependence of P-wave dispersion on mean arterial pressure as an independent
      hemodynamic variable in school children.
AB  - INTRODUCTION: The relationship between diastolic dysfunction and P-wave
      dispersion (PWD) in the electrocardiogram has been studied for some time. In this
      regard, echocardiography is emerging as a diagnostic tool to improve risk
      stratification for mild hypertension. OBJECTIVE: To determine the dependence of
      PWD on the electrocardiogram and on echocardiographic variables in a pediatric
      population. METHODS: 515 children from three elementary schools were studied from
      a total of 565 children. Those whose parents did not want them to take part in
      the study, as well as those with known congenital diseases, were excluded. Tests
      including 12-lead surface ECGs and 4 blood pressure (BP) measurements were
      performed. Maximum and minimum P-values were measured, and the PWD on the
      electrocardiogram was calculated. Echocardiography for structural measurements
      and the pulsed Doppler of mitral flow were also performed. RESULTS: A significant
      correlation in statistical variables was found between PWD and mean BP for pre
      hypertensive and hypertensive children, i.e., r = 0.32, p <0.01 and r = 0.33, p
      <0.01, respectively. There was a significant correlation found between PWD and
      the left atrial area (r = 0.45 and p <0.01). CONCLUSIONS: We highlight the
      dependency between PWD, the electrocardiogram and mean blood pressure. We also
      draw attention to the dependence of PWD on the duration of the mitral inflow A
      wave. This result provides an explanation for earlier changes in atrial
      electrophysiological and hemodynamic characteristics in pediatric patients.

PMID- 24892617
TI  - Prediction of prolonged mechanical ventilation in patients in the intensive care
      unit A cohort study.
AB  - INTRODUCTION: There are no established guidelines for selecting patients for
      early tracheostomy. The aim was to determine the factors that could predict the
      possibility of intubation longer than 7 days in critically ill adult patients.
      METHODS: This is cohort study made at a general intensive care unit. Patients who
      required at least 48 hours of mechanical ventilation were included. Data on the
      clinical and physiologic features were collected for every intubated patient on
      the third day. Uni- and multivariate statistical analyses were conducted to
      determine the variables associated with extubation. RESULTS: 163 (62%) were male,
      and the median age was 59+/-17 years. Almost one-third (36%) of patients required
      mechanical ventilation longer than 7 days. The variables strongly associated with
      prolonged mechanical ventilation were: age (HR 0.97 (95% CI 0.96-0.99); diagnosis
      of surgical emergency in a patient with a medical condition (HR 3.68 (95% CI 1.62
      8.35), diagnosis of surgical condition-non emergency (HR 8.17 (95% CI 2.12-31.3);
      diagnosis of non-surgical-medical condition (HR 5.26 (95% CI 1.85-14.9); APACHE
      II (HR 0.91 (95% CI 0.85-0.97) and SAPS II score (HR 1.04 (95% CI 1.00-1.09) The
      area under ROC curve used for prediction was 0.52. 16% of patients were extubated
      after day 8 of intubation. CONCLUSIONS: It was not possible to predict early
      extubation in critically ill adult patients with invasive mechanical ventilation
      with common clinical scales used at the ICU. However, the probability of
      successfully weaning patients from mechanical ventilation without a tracheostomy
      is low after the eighth day of intubation.

PMID- 24892618
TI  - Synthetic dural graft septoplasty in epistaxis from hereditary hemorrhagic
      telangiectasia.
AB  - It is an autosomal dominant vascular disorder, which has a variety of clinical
      manifestations, with epistaxis being one of the most common. Many treatment
      options exist for epistaxis, but with no consensus on which is the method of
      choice. We describe the case of a patient with hereditary hemorrhagic
      telangiectasia (HHT) secondary epistaxis with septoplasty managed with synthetic
      hard graft, which improved intensity and frequency of bleeding episodes. This
      technique is a variant of the septodermoplasty described by several authors, but
      the use of synthetic dura can help in obtaining better results and avoid taking
      skin grafts from other sites different from the surgical site. 

PMID- 24892620
TI  - Umbilical-spinous line: a morphological term that should be included in the
      anatomical terminology.
AB  - We argue the need to include in the International Anatomical Terminology the term
      "Umbilical-spinous line" for its importance as a morphological referent in
      bioscopic and surface anatomy. Also, in order to avoid using eponyms, it is
      suggested that the traditional term "McBurney point" be replaced by "supra
      spinous point" as being more descriptive of location. 

PMID- 24892621
TI  - International accreditation and quality medical education; the need for
      establishment in middle east.

PMID- 24892619
TI  - Gastric cancer: Overview.
AB  - Gastric cancer ranks fourth in incidence and second in mortality among all
      cancers worldwide. Despite the decrease in incidence in some regions of the
      world, gastric cancer continues to present a major clinical challenge due to most
      cases being diagnosed in advanced stages with poor prognosis and limited
      treatment options. The development of gastric cancer is a complex and
      multifactorial process involving a number of etiological factors and multiple
      genetic and epigenetic alterations. Among the predisposing factors are:
      Helicobacter pylori infection, high salt intake, smoking, and in a small
      percentage of patients, a familial genetic component. More than 95% of stomach
      cancer cases are adenocarcinomas, which are classified into two major histologic
      types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a
      sequence of gastric lesions known as Correa's cascade and is the histologic type
      associated with the global decrease in gastric cancer rates. Diffuse type
      adenocarcinomas have a more aggressive behavior and worse prognosis than those of
      the intestinal type. According to the anatomical location, adenocarcinomas are
      classified as proximal (originating in the cardia) and distal (originating in the
      body and antrum). This classification seems to recognize two different clinical
      entities. Surgical resection of the tumor at an early stage is the only effective
      treatment method. Therefore, the identification and surveillance of patients at
      risk may play a significant role in survival rates. Anti-Helicobacter pylori
      therapy has been shown to be an effective measure in the prevention of gastric
      cancer. 

PMID- 24892622
TI  - DOTAP functionalizing single-walled carbon nanotubes as non-viral vectors for
      efficient intracellular siRNA delivery.
AB  - CONTEXT: Functionalized single-walled carbon nanotubes (SWNT) with 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP) were used as novel and more convenient carriers
      of small interfering RNA (siRNA). OBJECTIVE: To utilize the unique capability of
      SWNT to be easily modified by functional groups and readily internalized by
      mammalian cells to bind, condense, stabilize siRNA and enhance its transfection
      efficiency. METHODS: After SWNT were non-covalently functionalized by cationic
      DOTAP (SWNT-DOTAP), siRNA interacted with SWNT-DOTAP via static electricity (SWNT
      DOTAP/siRNA). Subsequently, the size, zeta potential and morphology of SWNT
      DOTAP/siRNA were analyzed. The optimal compression ratio and stability of siRNA
      were assessed by agarose gel electrophoresis. Furthermore, in prostate carcinoma
      PC-3 cells, RT-PCR, flow cytometry and sulforhodamine B assays were used to
      evaluate the silencing activity, transfection efficiency and cell proliferation,
      respectively. RESULTS AND DISCUSSION: The characteristics of SWNT-DOTAP, i.e. an
      average size of 194.49 nm, a zeta potential of 45.16 mV and lower cytotoxicity
      than Lipofectamine 2000, indicated that this vector was suitable for siRNA
      delivery. Moreover, after interaction with SWNT-DOTAP, siRNA of human telomerase
      reverse transcriptase was bound, condensed and stabilized. In PC-3 cells, SWNT
      DOTAP/siRNA exhibited 82.6% silencing activity and 92% transfection efficiency.
      Furthermore, the complexes inhibited cell proliferation by 42.1%. CONCLUSION:
      SWNT-DOTAP may be a promising siRNA delivery vector for gene-based therapeutic
      applications in cancer.

PMID- 24892623
TI  - Phospholipid microemulsion-based hydrogel for enhanced topical delivery of
      lidocaine and prilocaine: QbD-based development and evaluation.
AB  - Topical delivery of local anesthetics has been an area of interest for
      researchers considering the barrier properties of skin and unfavorable
      physicochemical properties of drugs. In the present study, efforts have been made
      to modify the in vivo efficacy of eutectic mixture of lidocaine and prilocaine by
      exploiting the phospholipid modified microemulsion based delivery systems. The
      strategic QbD (D-optimal mixture design) enabled systematic optimization
      approach, after having obtained the isotropic area of interest by ternary phase
      diagram, has resulted into the system with most desirable attributes. Latter
      include nano-scale, globular structures with an average size of 40.6 nm, as
      characterized by TEM and DLS. The optimized microemulsion systems in gel dosage
      forms revealed the better permeability over commercial cream (CC) through
      abdominal rat skin. Enhancement in the flux from MOPT-NMP gel was 3.22-folds for
      prilocaine and 4.94-folds for lidocaine, in comparison to that of CC. This
      enhanced skin permeability is very well reflected in the in vivo studies, wherein
      intensity and duration of action was augmented significantly. The skin compliance
      of the optimized formulation was revealed in histopathological studies. The
      overall benefit relating to efficacy and safety-compliance could be correlated to
      the uniqueness of the carriers, composed of phospholipids and other components.
      Hence, the developed phospholipid-microemulsion based gel formulation has been
      proposed as more useful alternative for the topical delivery of lidocaine and
      prilocaine. 

PMID- 24892625
TI  - Colloidal drug delivery system: amplify the ocular delivery.
AB  - CONTEXT: The ocular perceivers are the most voluntarily accessible organs in
      terms of location in the body, yet drug distribution to these tissues is one of
      the most intriguing and challenging endeavors and problematic to the
      pharmaceutical scientist. The most of ocular diseases are treated with topical
      application of conventional formulation, i.e. solutions, suspensions and
      ointment. Typically on installation of these conventional formulations, only <5%
      of the applied dose penetrates the cornea and reaches intraocular tissues, while
      a major fraction of the instilled dose is wastage due to the presence of many
      ocular barriers like external barriers, rapid loss of the instilled solution from
      the precorneal area and nasolacrimal drainage system. Systemic absorption caused
      systemic side effects varying from mild to life-threatening events. OBJECTIVE:
      The main objective of this review is to explore the role of colloidal delivery of
      drug to minimize the drawbacks associated with them. METHODS: This review
      provides an insight into the various constraints associated with ocular drug
      delivery, summarizes recent findings and applications of colloidal delivery
      systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and
      contact lenses containing nanoparticles have the capacity to distribute ocular
      drugs to categorical target sites and hold promise to revolutionize the therapy
      of many ocular perceiver diseases and minimized the circumscription of
      conventional delivery. CONCLUSION: Form the basis of literature review, it has
      been found that the novel delivery system have greater impact to maximize ocular
      drug absorption, and minimize systemic absorption and side effects.

PMID- 24892624
TI  - Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro
      and in vivo evaluation studies.
AB  - In the present study controlled release effervescent buccal discs of buspirone
      hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive
      polymer by direct compression method. Sodium bicarbonate and citric acid were
      used in varying amounts as effervescence forming agents. Carbon dioxide evolved
      due to reaction of sodium bicarbonate and citric acid was explored for its
      potential as buccal permeation enhancer. The designed buccal discs were evaluated
      for physical characteristics and in vitro drug release studies. Bioadhesive
      behavior of designed buccal discs was assessed using texture analyzer. In vivo
      animal studies were performed in rabbits to study bioavailability of BS in the
      designed buccal discs and to establish permeation enhancement ability of carbon
      dioxide. It was observed that effervescent buccal discs have faster drug release
      compared to non-effervescent buccal discs in vitro and effervescent buccal discs
      demonstrated significant increase in bioavailability of drug when compared to non
      effervescent formulation. Hence, effervescent buccal discs can be used as an
      alternative to improve the drug permeation resulting in better bioavailability.
      However, the amount of acid and base used for generation of carbon dioxide should
      be selected with care as this may damage the integrity of bioadhesive dosage
      form. 

PMID- 24892626
TI  - Buccal films of prednisolone with enhanced bioavailability.
AB  - The conventional formulation of prednisolone is considered to be low in efficacy,
      primarily on account of their failure in providing and maintaining effective
      therapeutic drug levels. This study aims to focus on development of a
      mucoadhesive buccal delivery system with a twofold objective of offering a rapid
      as well as a prolonged delivery of prednisolone coupled with enhanced therapeutic
      efficacy. Buccoadhesive films of prednisolone were prepared by solvent-casting
      method using hydroxyl propyl methyl cellulose (K100), Carbopol 940 and/or
      Eudragit NE 40 D. Placebo films possessing the most desirable physicomechanical
      properties were selected for drug loading. The effect of polymer and its content
      on film properties, i.e. mucoadhesive strength, swelling and hydration, in vitro
      drug release was studied. Based on these studies, film F7D was selected for ex
      vivo permeation across porcine cheek mucosa. The steady state flux of
      prednisolone across the buccal mucosa was found to be 105.33 +/- 32.07
      ug/cm(2)/h. A comparative pharmacokinetic study of prepared film (F7D) and oral
      suspension of prednisolone was conducted. In vivo data of buccal film show
      greater bioavailability (AUC0-alpha: 24.26 +/- 4.06 ug.h/ml versus 10.65 +/- 2.15
      ug.h/ml) and higher Cmax (2.70 +/- 0.38 ug/ml versus 2.29 +/- 0.32 ug/ml) value
      when compared to oral suspension. The data observed from this study highlight the
      feasibility of the buccal route as a viable option for delivery of prednisolone.

PMID- 24892628
TI  - Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo
      oral bioavailability and in situ intestinal absorption of curcumin.
AB  - PURPOSE: The present study was to formulate curcumin solid lipid nanoparticles
      (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the
      solubility and bioavailability of curcumin. METHODS: The formulation was
      optimized by Plackett-Burman screening design and Box-Behnken experiment design.
      Then physiochemical properties, entrapment efficiency and in vitro release of Cur
      SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass
      intestinal perfusion were performed to investigate the effects of Cur-SLNs on the
      bioavailability and intestinal absorption of curcumin. RESULTS: The optimized
      formulations showed an average size of 135.3 +/- 1.5 nm with a zeta potential
      value of -24.7 +/- 2.1 mV and 91.09% +/- 1.23% drug entrapment efficiency,
      meanwhile displayed a sustained release profile. In vivo pharmacokinetic study
      showed AUC0->t for Cur-SLNs was 12.27-folds greater than curcumin suspension and
      the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2)
      of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p <
      0.01). The in situ intestinal absorption study revealed that the effective
      permeability (Peff) value of curcumin for SLNs was significantly improved (p <
      0.01) comparing to curcumin solution. CONCLUSION: Cur-SLNs with TPGS and Brij78
      could improve the oral bioavailability and intestinal absorption of curcumin
      effectively.

PMID- 24892627
TI  - Efficient delivery of micro RNA to bone-metastatic prostate tumors by using
      aptamer-conjugated atelocollagen in vitro and in vivo.
AB  - Bone is the primary site of skeletal metastasis in prostate cancer (PCa).
      Atelocollagen (ATE)-mediated siRNA delivery system can be used to silence
      endogenous genes involved in PCa metastatic tumor cell growth. However, we hope
      that the delivery system can target PCa cells to reduce damage to the bone tissue
      and improve the therapeutic effect. RNA aptamer (APT) A10-3.2 has been used as a
      ligand to target PCa cells that express prostate-specific membrane antigen
      (PSMA). APT was investigated as a PSMA-targeting ligand in the design of an ATE
      based microRNA (miRNA; miR-15a and miR-16-1) vector to PCa bone metastasis. To
      observe the targeted delivery and transfection efficiency of ATE-APT in PSMA
      overexpressing cells, luciferase activity and biodistribution of nanoparticles in
      Balb/c mice was analyzed. The anticancer effect of nanoparticles in vivo was
      investigated using the survival times of human PCa bone metastasis mice model.
      Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+))
      cells showed that the transfection efficiency of the synthesized DNA/ATE-APT
      complex was higher than that of the DNA/ATE complex. The anticancer efficacy of
      miRNA/ATE-APT was superior to those of other treatments in vivo. This PSMA
      targeted system may prove useful in widening the therapeutic window and allow for
      selective killing of PCa cells in bone metastatic foci. 

PMID- 24892629
TI  - Preparation and in vitro/in vivo evaluation of esomeprazole magnesium-modified
      release pellets.
AB  - To reduce the drug plasma concentration fluctuation without being destroyed by
      gastric fluid, novel Esomeprazole magnesium modified-release pellets (EMZ-MRPs)
      with suitable in vitro release profiles and good in vitro and in vivo correlation
      (IVIVC) were developed. Fluid-bed was used to obtain EMZ-loaded pellets by
      spraying drug suspension onto blank sugar pellets. The drug-loaded pellets were
      subsequently coated with Eudragit(r) RS30D/RL30D (ERS/ERL) aqueous dispersion to
      achieve sustained-release (SR) characteristics. Furthermore, the SR pellets were
      coated with Eudragit(r) L30D-55 (EL-55) aqueous dispersion to achieve enteric
      properties. Besides, isolated coating film was necessary between drug layer and
      SR layer, as well as SR and enteric-coated layer to protect from their possible
      reaction. The resulting pellets were filled into the hard gelatin capsules for in
      vitro release processing and single-dose pharmacokinetic study in rats. The
      optimal formulation achieved good SR feature both in vitro and in vivo with a
      relative bioavailability of 103.50%. A good IVIVC was characterized by a high
      coefficient of determination (r = 0.9945) by deconvolution method. Compared to
      those of EMZ enteric-coated pellets (EMZ-ECPs, trade name NEXIUM), the in vivo
      study make known that the EMZ-MRPs with decreased maximum plasma concentration
      (Cmax), prolonged peak concentration time (Tmax) and mean residence time (MRT),
      and similar values both area under concentration-time curve from 0 to t (AUC0-t)
      and 0 to infinity (AUC0-infinity). Collectively, these results manifested EMZ
      MRPs had a satisfactory sustained-release behavior, a desired pharmacokinetic
      property, improved in vivo retention and decreased plasma drug concentration
      fluctuation. 

PMID- 24892630
TI  - Use of biorelevant media for assessment of a poorly soluble weakly basic drug in
      the form of liquisolid compacts: in vitro and in vivo study.
AB  - The purpose of this work is to use biorelevant media to evaluate the robustness
      of a poorly water soluble weakly basic drug to variations along the
      gastrointestinal tract (GIT) after incorporation in liquisolid compacts and to
      assess the success of these models in predicting the in vivo performance.
      Liquisolid tablets were prepared using mosapride citrate as a model drug. A
      factorial design experiment was used to study the effect of three factors,
      namely: drug concentration at two levels (5% and 10%), carriers at three levels
      (avicel, mannitol and lactose) and powder excipients ratio (R) of the coating
      material at two levels (25 and 30). The in vitro dissolution media utilized were
      0.1 N HCl, hypoacidic stomach model and a transfer model simulating the transfer
      from the stomach to the intestine. All compacts released above 95% of drug after
      10 min in 0.1 N HCl. In the hypoacidic model, the compacts with R 30 were
      superior compared to R 25, where they released >90% of drug after 10 min compared
      to 80% for R 25. After the transfer of the optimum compacts from Simulated
      gastric fluid fast (SGFfast) to fasted state simulated intestinal fluid, slight
      turbidity appeared after 30 min, and the amount of drug dissolved slightly
      decreased from 96.91% to 90.59%. However, after the transfer from SGFfast to fed
      state simulated intestinal fluid, no turbidity or precipitation occurred
      throughout time of the test (60 min). In vivo pharmacokinetic study in human
      volunteers proved the success of the in vitro models with enhancement of the oral
      bioavailability (121.20%) compared to the commercial product. 

PMID- 24892631
TI  - Design of freeze-dried Soluplus/polyvinyl alcohol-based film for the oral
      delivery of an insoluble drug for the pediatric use.
AB  - Spironolactone (SL) is a poorly water-soluble drug. Being poorly soluble affects
      its dissolution rate which in turn affects its oral bioavailability. This work
      aimed to prepare freeze-dried SL-Soluplus/polyvinyl alcohol (PVA) oral thin film
      in an attempt to enhance the drug solubility on one hand and at the same time
      prepare a solid dosage form convenient for the pediatric use. SL-Soluplus/PVA
      films were prepared using polyethylene glycol 400 (PEG 400) as a plasticizer
      applying the solvent-casting technique. The prepared films were evaluated for
      their thickness, tensile strength, and in vitro dissolution studies. Box-Behnken
      design (17 runs) was applied to optimize the effects of the formulation variables
      on the film properties. The optimized film formulation was freeze-dried after
      casting so as to enhance the drug dissolution. Moreover, the optimized freeze
      dried film was re-characterized in vitro and evaluated in vivo in human
      volunteers to investigate its palatability and satisfaction. The results showed
      that the optimized formulation composed of 10% polymer concentration containing
      Soluplus:PVA (0.33:0.66) and plasticized with 30% PEG 400 possessed the highest
      desirability value (0.836). Freeze-drying of the optimized formulation succeeded
      to improve SL in vitro dissolution due to the preparation of a more porous film
      compared to the non-freeze-dried one. In vivo evaluation of the optimized freeze
      dried film showed high satisfaction among the participating volunteers concerning
      the ease of administration and sensation thereafter, where all the film specimens
      dissolved without the need for water and no film residues remained in the mouth
      following film dissolution. In conclusion, freeze-dried Soluplus(r)/PVA-based
      oral thin film proved to be a successful carrier for the oral delivery of
      insoluble drugs like SL for pediatrics.

PMID- 24892632
TI  - Design of novel multifunctional targeting nano-carrier drug delivery system based
      on CD44 receptor and tumor microenvironment pH condition.
AB  - In this study, to develop a multifunctional targeting nano-carrier drug delivery
      system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of
      hyaluronan (oHA) conjugates were synthesized by chemical conjugation of
      hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the
      histidine as the linker of proton sponge effect. The multifunctional oHA
      conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic
      moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to
      nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS
      conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin
      (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of
      cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable
      and have less toxicity compared to Cur suspension. The anti-tumor efficacy in
      vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These
      results present the promising potential of oHMN as a stable and effective nano
      sized pH-sensitive drug delivery system for cancer treatment. 

PMID- 24892634
TI  - ABM, WABA, and breastfeeding support.

PMID- 24892633
TI  - Omega 3 fatty acid-enriched nanoemulsion of thiocolchicoside for transdermal
      delivery: formulation, characterization and absorption studies.
AB  - Thiocolchicoside (TCC) is an effective therapeutic agent against the orthopaedic,
      traumatic and rheumatologic disorders but it suffer from the drawback of poor
      bioavailability due to extensive first pass metabolism and low permeability via
      the oral route. The aim of the present study was to evaluate the potential of
      nanoemulsion (NE) for bioavailability enhancement of TCC through the transdermal
      route. The NEs were developed using Linseed: sefsol in 1:1 ratio as the oil
      phase, span 80, Transcutol P and distilled water as surfactant, co-surfactant and
      aqueous phase. Furthermore, selected formulations were subjected to physical
      stability and consequently evaluated for in vitro permeation using porcine skin.
      The optimized formulation had small average globule diameter of 117 nm with
      polydispersity index of 0.285. The globules were spherical in shape as observed
      by transmission electron microscopy. The in vitro skin permeation profile of
      optimized NE was compared with aqueous solution of TCC. Significant increase in
      permeability parameters were observed in NEs formulation (p < 0.05) as compared
      to aqueous solution of TCC. The steady-state flux (Jss) and permeability
      coefficient (Kp) for optimized NE formulation (C1) were found to be 30.63 +/-
      4.18 ug/cm(2)/h and 15.21 * 10(-3) +/- 2.81cm(2)/h, respectively. The results of
      enhanced permeation through transdermal route suggest that water-in-oil NEs which
      are compatible with the lipophilic sebum environment of the hair follicle
      facilitate the transport of TCC, and such transport might be predominantly
      transfollicular in nature. Overall, these results suggested that water-in-oil NEs
      are good carriers for transdermal delivery of TCC.

PMID- 24892635
TI  - Addressing addiction across borders: an international perspective on policies,
      scholarship, and collaboration.

PMID- 24892637
TI  - Naturally occurring mutants inform SHBG structure and function.
AB  - SHBG transports and regulates the activities of androgens and estrogens. Several
      single nucleotide polymorphisms in the human SHBG gene have been linked to sex
      steroid-dependent diseases, including those associated with the metabolic
      syndrome. The N-terminal laminin G-like domain of SHBG includes binding sites for
      calcium, sex steroids, and fibulin family members, as well as a dimerization
      domain. We have found that 8 of 18 uncharacterized nonsynonymous single
      nucleotide polymorphisms within this domain alter the production or biochemical
      properties of SHBG in ways not previously recognized. O-Linked glycosylation at
      Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E
      limits its secretion. Three SHBG mutants (R135C, L165M, and E176K) bind estradiol
      with abnormally high affinity. SHBG R135C also has an increased interaction with
      fibulin-2. Two different substitutions within the dimer interface at R123 (R123H
      and R123C) reduce the affinity for 5alpha-dihydrotestosterone, while increasing
      the relative binding affinity for estradiol. SHBG T48I is defective in calcium
      binding, which leads to a defect in dimerization, reduced affinity for sex
      steroids, and an enhanced interaction with fibulin-2, which can all be restored
      by calcium supplementation. These naturally occurring mutants provide insight
      into SHBG structure and function, and defects in SHBG production or function need
      to be considered in the context of its utility as a biomarker of diseases. 

PMID- 24892639
TI  - DNA repair gene variants in migraine.
AB  - AIMS: Migraine is a common and debilitating episodic disorder characterized by
      recurrent headache attacks associated with autonomic symptoms. It affects an
      estimated 12% of the population. The etiology of the underlying neurodegenerative
      process is widely unknown; however, oxidative stress is a unifying factor in the
      current theories of migraine pathogenesis. After demonstrating the observation
      that oxidative DNA damage is detectable in migraine disease, searching the role
      played by DNA repair systems in migraine diseases could bring us much significant
      information about the pathogenesis of migraine. We prospectively investigated
      whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD
      Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, hOGG1 Ser326Cys) account for an
      increased risk of migraine. The present analyses are based on 135 case subjects
      with migraine disease and 101 noncase subjects. Genotyping of DNA repair gene
      polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His,
      APE1 Asp148Glu, hOGG1 Ser326Cys) was detected by polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: We demonstrated that apurinic
      endonuclease (APE), X-ray repair complementing defective repair in Chinese
      hamster cells 3 (XRCC3), xeroderma pigmentosum D (XPD), and hOGG1 gene variants
      were associated with an increased risk for development of migraine disease
      (p<0.05). In contrast, no statistically significant differences were found in
      genotype distributions of X-ray repair complementing defective repair in Chinese
      hamster cells 1 (XRCC1) and XPG between migraine cases and controls (p>0.05).
      CONCLUSIONS: Our findings have suggested that APE1, XRCC3, XPD, and hOGG1 gene
      variants could facilitate the development of migraine disease.

PMID- 24892640
TI  - Electrochemically tunable thermal conductivity of lithium cobalt oxide.
AB  - Using time-domain thermoreflectance, the thermal conductivity and elastic
      properties of a sputter deposited LiCoO2 film, a common lithium-ion cathode
      material, are measured as a function of the degree of lithiation. Here we report
      that via in situ measurements during cycling, the thermal conductivity of a
      LiCoO2 cathode reversibly decreases from ~5.4 to 3.7 W m(-1) K(-1), and its
      elastic modulus decreases from 325 to 225 GPa, as it is delithiated from
      Li1.0CoO2 to Li0.6CoO2. The dependence of the thermal conductivity on lithiation
      appears correlated with the lithiation-dependent phase behaviour. The oxidation
      state-dependent thermal conductivity of electrolytically active transition metal
      oxides provides opportunities for dynamic control of thermal conductivity and is
      important to understand for thermal management in electrochemical energy storage
      devices.

PMID- 24892636
TI  - The tumor-associated marker, PVRL4 (nectin-4), is the epithelial receptor for
      morbilliviruses.
AB  - PVRL4 (nectin-4) was recently identified as the epithelial receptor for members
      of the Morbillivirus genus, including measles virus, canine distemper virus and
      peste des petits ruminants virus. Here, we describe the role of PVRL4 in
      morbillivirus pathogenesis and its promising use in cancer therapies. This
      discovery establishes a new paradigm for the spread of virus from lymphocytes to
      airway epithelial cells and its subsequent release into the environment. Measles
      virus vaccine strains have emerged as a promising oncolytic platform for cancer
      therapy in the last ten years. Given that PVRL4 is a well-known tumor-associated
      marker for several adenocarcinoma (lung, breast and ovary), the measles virus
      could potentially be used to specifically target, infect and destroy cancers
      expressing PVRL4. 

PMID- 24892641
TI  - Determining the satisfaction levels of the family members of patients with
      advanced-stage cancer.
AB  - OBJECTIVE: The objective of our study was to determine the satisfaction levels of
      family members of patients with advanced-stage cancer. METHOD: This descriptive
      study was conducted in the palliative care and medical oncology clinics of a
      university hospital in the province of Izmir between April of 2011 and January of
      2012. The study sample consisted of a total of 145 family members, who were
      selected from among the family members of patients with advanced-stage cancer
      receiving palliative treatment. The study data were obtained using the Patient
      Description Form and Family Satisfaction Scale during face-to-face interviews
      with patients. RESULTS: Some 67% of patients were female and 33% male, 70% were
      married, 35% were high school graduates, and 34.5% were housewives. The average
      total family satisfaction score was 76.87 +/- 1.14, and the average scores for
      the component variables were as follows: information giving 74.37 +/- 1.28,
      availability of care 78.40 +/- 1.17, physical care 78.99 +/- 1.09, and
      psychosocial care 74.52 +/- 1.30. We found a relationship between the level of
      satisfaction of family members and (1) gender, (2) occupation, (3) presence of
      someone supporting the care, and (4) possession of sufficient information about
      the patient (p < 0.05). SIGNIFICANCE OF RESULTS: Satisfaction levels of
      participants were determined to be high. We found that family member satisfaction
      levels were affected by gender and occupation, the existence of someone
      supporting the care, and possession of sufficient information about the patient.

PMID- 24892642
TI  - Re: Editorial comment on constitutional, organopathic and combined homeopathic
      treatment of benign prostatic hypertrophy: a clinical trial: S. A. Kaplan J Urol
      2013; 190: 1818-1819.

PMID- 24892644
TI  - Editorial comment.

PMID- 24892638
TI  - Minireview: Gut microbiota: the neglected endocrine organ.
AB  - The concept that the gut microbiota serves as a virtual endocrine organ arises
      from a number of important observations. Evidence for a direct role arises from
      its metabolic capacity to produce and regulate multiple compounds that reach the
      circulation and act to influence the function of distal organs and systems. For
      example, metabolism of carbohydrates results in the production of short-chain
      fatty acids, such as butyrate and propionate, which provide an important source
      of nutrients as well as regulatory control of the host digestive system. This
      influence over host metabolism is also seen in the ability of the prebiotic
      inulin to influence production of relevant hormones such as glucagon-like peptide
      1, peptide YY, ghrelin, and leptin. Moreover, the probiotic Lactobacillus
      rhamnosus PL60, which produces conjugated linoleic acid, has been shown to reduce
      body-weight gain and white adipose tissue without effects on food intake.
      Manipulating the microbial composition of the gastrointestinal tract modulates
      plasma concentrations of tryptophan, an essential amino acid and precursor to
      serotonin, a key neurotransmitter within both the enteric and central nervous
      systems. Indirectly and through as yet unknown mechanisms, the gut microbiota
      exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from
      studies on animals raised in a germ-free environment, who show exaggerated
      responses to psychological stress, which normalizes after monocolonization by
      certain bacterial species including Bifidobacterium infantis. It is tempting to
      speculate that therapeutic targeting of the gut microbiota may be useful in
      treating stress-related disorders and metabolic diseases. 

PMID- 24892645
TI  - Place and cause of death in centenarians: a population-based observational study
      in England, 2001 to 2010.
AB  - BACKGROUND: Centenarians are a rapidly growing demographic group worldwide, yet
      their health and social care needs are seldom considered. This study aims to
      examine trends in place of death and associations for centenarians in England
      over 10 years to consider policy implications of extreme longevity. METHODS AND
      FINDINGS: This is a population-based observational study using death registration
      data linked with area-level indices of multiple deprivations for people aged
      >=100 years who died 2001 to 2010 in England, compared with those dying at ages
      80-99. We used linear regression to examine the time trends in number of deaths
      and place of death, and Poisson regression to evaluate factors associated with
      centenarians' place of death. The cohort totalled 35,867 people with a median age
      at death of 101 years (range: 100-115 years). Centenarian deaths increased 56%
      (95% CI 53.8%-57.4%) in 10 years. Most died in a care home with (26.7%, 95% CI
      26.3%-27.2%) or without nursing (34.5%, 95% CI 34.0%-35.0%) or in hospital
      (27.2%, 95% CI 26.7%-27.6%). The proportion of deaths in nursing homes decreased
      over 10 years (-0.36% annually, 95% CI -0.63% to -0.09%, p = 0.014), while
      hospital deaths changed little (0.25% annually, 95% CI -0.06% to 0.57%, p =
      0.09). Dying with frailty was common with "old age" stated in 75.6% of death
      certifications. Centenarians were more likely to die of pneumonia (e.g., 17.7%
      [95% CI 17.3%-18.1%] versus 6.0% [5.9%-6.0%] for those aged 80-84 years) and old
      age/frailty (28.1% [27.6%-28.5%] versus 0.9% [0.9%-0.9%] for those aged 80-84
      years) and less likely to die of cancer (4.4% [4.2%-4.6%] versus 24.5% [24.6%
      25.4%] for those aged 80-84 years) and ischemic heart disease (8.6% [8.3%-8.9%]
      versus 19.0% [18.9%-19.0%] for those aged 80-84 years) than were younger elderly
      patients. More care home beds available per 1,000 population were associated with
      fewer deaths in hospital (PR 0.98, 95% CI 0.98-0.99, p<0.001). CONCLUSIONS:
      Centenarians are more likely to have causes of death certified as pneumonia and
      frailty and less likely to have causes of death of cancer or ischemic heart
      disease, compared with younger elderly patients. To reduce reliance on hospital
      care at the end of life requires recognition of centenarians' increased
      likelihood to "acute" decline, notably from pneumonia, and wider provision of
      anticipatory care to enable people to remain in their usual residence, and
      increasing care home bed capacity.

PMID- 24892646
TI  - Differences between young and older adults in the control of weight shifting
      within the surface of support.
AB  - An important reason for falling in elderly is incorrect weight-shifting. In many
      daily life activities quick and accurate weight-shifting is needed to maintain
      balance and to prevent from falling. The present study aims to gain more insight
      in age-related differences in the control of weight-shifting. Nine healthy older
      adults (70.3 +/- 6.9 years) and twelve young adults (20.9 +/- 0.5 years)
      participated in the study. They performed a weight shifting task by moving the
      body's center of pressure, represented by a red dot on a screen, in different
      directions, towards targets of different sizes and at different distances
      projected on a screen. Movement time, fluency and accuracy of the movement were
      determined. Accuracy was quantified by the number of times the cursor hit the
      goal target before a target switch was realized (counts on goal) and by the time
      required to realize a target switch after the goal target was hit by the cursor
      for the first time (dwelling time). Fluency was expressed by the maximal
      deviation of the performed path with respect to the ideal path and the number of
      peaks, or inflections in the performed path. Significant main effects of target
      size, target distance and age on all outcome measures were found. With decreasing
      target size, increasing target distance and increasing age, movement time
      significantly increased and fluency and accuracy significantly decreased (i.e.
      increased number of peaks, maximal deviation, number of times on the goal target
      and longer dwelling time around the goal target). In addition, significant
      interaction effects of size*age and distance*age were found. Older adults needed
      more time to perform the weight-shifting task and their movements were less
      fluent and accurate compared to younger adults, especially with increasing task
      difficulty. This indicates that elderly might have difficulties with executing an
      adequate adaptation to a perturbation in daily life.

PMID- 24892647
TI  - Shaking alone induces de novo conversion of recombinant prion proteins to beta
      sheet rich oligomers and fibrils.
AB  - The formation of beta-sheet rich prion oligomers and fibrils from native prion
      protein (PrP) is thought to be a key step in the development of prion diseases.
      Many methods are available to convert recombinant prion protein into beta-sheet
      rich fibrils using various chemical denaturants (urea, SDS, GdnHCl), high
      temperature, phospholipids, or mildly acidic conditions (pH 4). Many of these
      methods also require shaking or another form of agitation to complete the
      conversion process. We have identified that shaking alone causes the conversion
      of recombinant PrP to beta-sheet rich oligomers and fibrils at near physiological
      pH (pH 5.5 to pH 6.2) and temperature. This conversion does not require any
      denaturant, detergent, or any other chemical cofactor. Interestingly, this
      conversion does not occur when the water-air interface is eliminated in the
      shaken sample. We have analyzed shaking-induced conversion using circular
      dichroism, resolution enhanced native acidic gel electrophoresis (RENAGE),
      electron microscopy, Fourier transform infrared spectroscopy, thioflavin T
      fluorescence and proteinase K resistance. Our results show that shaking causes
      the formation of beta-sheet rich oligomers with a population distribution ranging
      from octamers to dodecamers and that further shaking causes a transition to beta
      sheet fibrils. In addition, we show that shaking-induced conversion occurs for a
      wide range of full-length and truncated constructs of mouse, hamster and cervid
      prion proteins. We propose that this method of conversion provides a robust,
      reproducible and easily accessible model for scrapie-like amyloid formation,
      allowing the generation of milligram quantities of physiologically stable beta
      sheet rich oligomers and fibrils. These results may also have interesting
      implications regarding our understanding of prion conversion and propagation both
      within the brain and via techniques such as protein misfolding cyclic
      amplification (PMCA) and quaking induced conversion (QuIC). 

PMID- 24892648
TI  - Tumor-associated macrophages promote cancer stem cell-like properties via
      transforming growth factor-beta1-induced epithelial-mesenchymal transition in
      hepatocellular carcinoma.
AB  - Tumor-associated macrophages (TAMs), a crucial component of immune cells
      infiltrated in tumor microenvironment, have been found to be associated with
      progression and metastasis of hepatocellular carcinoma (HCC). In this study, we
      aimed to clarify the mechanism underlying the crosstalk between TAMs and cancer
      stem cells (CSCs) in HCC. Mouse macrophage cell line RAW264.7 cells were used to
      investigate the effects of TAMs on mouse hepatoma cell line Hepa1-6 cells in vivo
      and vitro. A total of 90 clinical samples had pathology-proven HCC were used to
      evaluate the distribution of TAMs and CSCs and analyze their value in predicting
      the prognosis. In the study, we have found that the number of TAMs has a positive
      correlation with the density of CSCs in the marginal of human HCC. Our results
      show that, cocultured with TAM-conditioned medium (CM) promoted CSC-like
      properties in Hepa1-6 cells, which underwent EMT and gained higher invasive
      capability. TAMs secreted more transforming growth factor- beta1 (TGF-beta1) than
      other phenotypes of macrophage. Furthermore, depletion of TGF-beta1 blocked
      acquisition of CSC-like properties by inhibition of TGF-beta1-induced EMT. High
      expression of CD68 in the EpCAM positive expression HCC tissues was strongly
      associated with both poor cancer-free survival and overall survival in patients.
      Our results indicate that the TAMs promote CSC-like properties via TGF-beta1
      induced EMT and they may contribute to investigate the prognosis of HCC.

PMID- 24892650
TI  - Novel strategy involving surfactant-polymer combinations for enhanced stability
      of aqueous teflon dispersions.
AB  - Among various polymers, the Teflon surface possesses extreme hydrophobicity (low
      surface energy), which is of great interest to both industry and academia. In
      this report, we discuss the stability of aqueous Teflon dispersions (particle
      size range of 100-3000 nm) formulated by a novel strategy that involves distinct
      combinations of surfactant and polymer mixtures for dispersion stabilization. As
      a first step, the hydrophobic Teflon particles were wetted using a range of
      surfactants (ionic, Triton, Brij, Tween, and Pluronic series) bearing different
      hydrophobic-lipophilic balance (HLB) and further characterized by contact angle
      and liquid penetration in packed powder measurements. The interaction between
      hydrophobic chains of surfactants and the Teflon particle surface is the driving
      force resulting in wetting of the Teflon particle surface. Further, these wetted
      particles in aqueous solutions were mixed with various polymers, for example,
      poly(vinyl alcohol) (PVA), polyvinylpyrrolidone (PVP), hydroxyethyl cellulose
      (HEC), and hydroxypropyl methyl cellulose (HPMC). The rate of sedimentation for
      the final dispersions was measured using a pan suspended into the dispersion from
      a transducer recording the increase in weight with time. A significant stability
      was noticed for Teflon particles suspended in surfactant + polymer mixtures,
      which was linearly proportional to the concentration of added polymer. The
      observed phenomenon can be possibly explained by molecular interactions between
      the hydrophobic chains of surfactant molecules and polar groups in the polymer
      architecture. Brij-O10 + HEC mixture was found to be the best surfactant-polymer
      combination for decreasing the sedimentation of the Teflon particles in the final
      dispersion. As measured by dynamic light scattering (DLS), the hydrodynamic
      volume of the Teflon particles increases up to ~55% in the final formulation.
      These dispersions could be further explored for various technological
      applications such as paints, inks, protective coatings, and so forth. 

PMID- 24892649
TI  - A network meta-analysis of the relative efficacy of treatments for actinic
      keratosis of the face or scalp in Europe.
AB  - BACKGROUND: Several treatments are available for actinic keratosis (AK) on the
      face and scalp. Most treatment modalities were compared to placebo and therefore
      little is known on their relative efficacy. OBJECTIVES: To compare the different
      treatments for mild to moderate AK on the face and scalp available in clinical
      practice in Europe. METHODS: A network meta-analysis (NMA) was performed on the
      outcome "complete patient clearance". Ten treatment modalities were included: two
      5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200
      ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three
      modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5%
      imiquimod, or a 2-3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3%
      in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB).
      The only data available for 5% 5-FU was from one small study and was determined
      to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL
      PDT, data from illumination with narrow-band lights were selected as these are
      typically used in clinical practice. The NMA was performed with a random-effects
      Bayesian model. RESULTS: 25 trials on 5,562 patients were included in the NMA.
      All active treatments were significantly better than placebo. BF-200 ALA showed
      the highest efficacy compared to placebo to achieve total patient clearance. BF
      200 ALA had the highest probability to be the best treatment and the highest
      SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5
      FU 0.5% (7.2% and 66.8%). CONCLUSIONS: This NMA showed that BF-200 ALA, using
      narrow-band lights, was the most efficacious treatment for mild to moderate AK on
      the face and scalp. This analysis is relevant for clinical decision making and
      health technology assessment, assisting the improved management of AK.

PMID- 24892652
TI  - Range-wide sex-chromosome sequence similarity supports occasional XY
      recombination in European tree frogs (Hyla arborea).
AB  - In contrast with mammals and birds, most poikilothermic vertebrates feature
      structurally undifferentiated sex chromosomes, which may result either from
      frequent turnovers, or from occasional events of XY recombination. The latter
      mechanism was recently suggested to be responsible for sex-chromosome homomorphy
      in European tree frogs (Hyla arborea). However, no single case of male
      recombination has been identified in large-scale laboratory crosses, and
      populations from NW Europe consistently display sex-specific allelic frequencies
      with male-diagnostic alleles, suggesting the absence of recombination in their
      recent history. To address this apparent paradox, we extended the phylogeographic
      scope of investigations, by analyzing the sequences of three sex-linked markers
      throughout the whole species distribution. Refugial populations (southern Balkans
      and Adriatic coast) show a mix of X and Y alleles in haplotypic networks, and no
      more within-individual pairwise nucleotide differences in males than in females,
      testifying to recurrent XY recombination. In contrast, populations of NW Europe,
      which originated from a recent postglacial expansion, show a clear pattern of XY
      differentiation; the X and Y gametologs of the sex-linked gene Med15 present
      different alleles, likely fixed by drift on the front wave of expansions, and
      kept differentiated since. Our results support the view that sex-chromosome
      homomorphy in H. arborea is maintained by occasional or historical events of
      recombination; whether the frequency of these events indeed differs between
      populations remains to be clarified. 

PMID- 24892653
TI  - Dry-land bilateral hand-force production and swimming performance in paralympic
      swimmers.
AB  - The effectiveness of human movement is the culmination of several musculoskeletal
      factors; asymmetry in movement could reduce optimal performance. The aims of this
      study were to quantify relationships between bilateral hand-force production,
      swimming performance, and the influence of fatigue. Paralympic swimmers (n=21,
      aged 20.9 +/- 4.7 yr) were categorised into no, high- and low-range physical
      disability groups and performed two 100 m time trials to measure swimming
      performance. Bilateral hand-force was measured over two 60 s maximal tests on a
      swim-bench ergometer to quantify the degree of asymmetry. Large relationships
      between mean force and swimming velocity were seen for both the high- (r=0.62, +/
      0.45; r-value, +/-90% confidence limits) and low-range (r=0.62, +/-0.50) groups.
      Asymmetry was related to level of disability, with the smallest difference of
      6.7, +/-2.6 N in the no-musculoskeletal disability group. This difference
      increased to 13.1, +/-10.0 N and 13.5, +/-16.2 N in the high- and low-range
      groups. Between the first and last 15 s of the swim-bench test, reductions in
      mean force were small for the physical disabilities groups. Similarly, changes in
      asymmetry were small for both the no-physical and low-range groups. Paralympic
      swimmers with a more severe physical impairment typically generate substantially
      lower force and velocity. 

PMID- 24892654
TI  - Which are the best VO2 sampling intervals to characterize low to severe swimming
      intensities?
AB  - Cardiorespiratory response in swimming has been used to better understand aerobic
      performance, especially by assessing oxygen uptake (VO2). The current study aimed
      to compare different VO2 time-averaging intervals throughout low to severe
      swimming intensities, hypothesizing that VO2 values are similar for different
      time averages at low to moderate and heavy swimming intensities, but not for the
      severe domain. 20 male trained swimmers completed an incremental protocol of
      7*200 m until exhaustion (0.05 m/s increments and 30 s intervals). VO2 was
      measured by a portable gas analyser connected to a snorkel system. 6 time average
      intervals (breath-by-breath, 5, 10, 15, 20 and 30 s) were compared for all the
      protocol steps. Breath-by-breath and 5 s average exhibited higher VO2 values than
      averages>=10 s for all swimming intensities (P<=0.02; partial eta(2)<=0.28). VO2
      values did not differ between 10, 15, 20 and 30 s averages throughout the
      incremental protocol (P>0.05; partial eta(2)<=0.05). Furthermore, 10 and 15 s
      averages showed the lowest VO2 mean difference (0.19 mL( . )kg(-1 . )min(-1)).
      For the 6 time average intervals analysed, 10 and 15 s averages were those that
      showed the lowest changes on VO2 values. We recommended the use of 10 and 15 s
      time averaging intervals to determine relevant respiratory gas exchange
      parameters along a large spectrum of swimming intensities. 

PMID- 24892651
TI  - Effect of bile pigments on the compromised gut barrier function in a rat model of
      bile duct ligation.
AB  - BACKGROUND: Studies have shown that the absence of bile in the gut lumen, either
      by bile duct ligation or bile diversion, induces mucosal injury. However, the
      mechanism remains elusive. In this study, the role of bile pigments in gut
      barrier function was investigated in a rat model of bile duct ligation. METHODS:
      Male Sprague Dawley (SD) rats were used in this study. After ligation of bile
      duct, the animals were administrated with free bilirubin, bilirubin ditaurate, or
      biliverdin by intragastric gavage. 1, 2, or 3 days later, the animals were
      sacrificed and the damage of mucosa was assessed by histological staining as well
      as biochemical parameters such as changes of diamine oxidase (DAO) and D-lactate
      (D-Lac) in the blood. Trypsin and chymotrypsin of the gut were also measured to
      determine how these digestive proteases may relate to the observed effects of
      bile pigments. RESULTS: Bile duct ligation (BDL) caused significant increases in
      gut trypsin and chymotrypsin along with damage of the mucosa as demonstrated by
      the histological findings under microscope, the reduced expression of tight
      junction molecules like occludin, and significant changes in DAO and D-lac in the
      blood. Free bilirubin but not bilirubin ditaurate or biliverdin showed
      significant inhibitions on trypsin and chymotrypsin as well as alleviated changes
      of histological and biochemical parameters related to gut barrier disruption.
      CONCLUSION: Bile may protect the gut from damage through inhibiting digestive
      proteases like trypsin and chymotrypsin by free bilirubin.

PMID- 24892655
TI  - Enhanced proton conductivity of Nafion hybrid membrane under different humidities
      by incorporating metal-organic frameworks with high phytic acid loading.
AB  - In this study, phytic acid (myo-inositol hexaphosphonic acid) was first
      immobilized by MIL101 via vacuum-assisted impregnation method. The obtained
      phytic@MIL101 was then utilized as a novel filler to incorporate into Nafion to
      fabricate hybrid proton exchange membrane for application in PEMFC under
      different relative humidities (RHs), especially under low RHs. High loading and
      uniform dispersion of phytic acid in MIL 101(Cr) were achieved as demonstrated by
      ICP, FT-IR, XPS, and EDS-mapping. The phytic@MIL101 was dispersed homogeneously
      in the Nafion matrix when the filler content was less than 12%. Hybrid membranes
      were evaluated by proton conductivity, mechanical property, thermal stability,
      and so forth. Remarkably, the Nafion/phytic@MIL hybrid membranes showed high
      proton conductivity at different RHs, especially under low RHs, which was up to
      0.0608 S cm(-1) and 7.63 * 10(-4) S cm(-1) at 57.4% RH and 10.5% RH (2.8 and 11.0
      times higher than that of pristine membrane), respectively. Moreover, the
      mechanical property of Nafion/phtic@MIL hybrid membranes was substantially
      enhanced and the thermal stability of membranes was well preserved. 

PMID- 24892656
TI  - Apoptosis induced by 2-aryl benzothiazoles-mediated photodynamic therapy in
      melanomas via mitochondrial dysfunction.
AB  - A mild and efficient synthetic development of 2-arylbenzothiazoles 5 mediated by
      ceric ammonium nitrate (CAN) via intramolecular cyclization of N-phenyl
      thiobenzamides 4 was achieved. Further compounds 5 were reduced to corresponding
      amines 6, and their photodynamic therapy (PDT) effect was evaluated on malignant
      human melanoma A375 cells. Amine 6l plus ultraviolet A (UVA) induced caspase-3
      activity, poly(ADP-ribose)polymerase cleavage, M30 positive CytoDeath staining,
      and subsequent apoptotic cell death. Our data disclosed that treatment of A375
      cells with 6l plus UVA resulted in a decrease in mitochondrial membrane potential
      (DeltaPsimt), oxidative phosphorylation system (OXPHOS) subunits, and adenosine
      triphosphate (ATP) but an increase in mitochondrial DNA 4977-bp deletion via
      reactive oxygen species (ROS) generation. Transmission electron microscopy (TEM)
      observations also showed major ultrastructural alterations of mitochondria.
      Additionally, 6l plus UVA was also shown to reduce murine melanoma size in a
      mouse model. The present study supports the hypothesis that 6l-PDT may serve as a
      potential ancillary modality for the treatment of melanoma. 

PMID- 24892657
TI  - Outcome probability versus magnitude: when waiting benefits one at the cost of
      the other.
AB  - Using a continuous impulsivity and risk platform (CIRP) that was constructed
      using a video game engine, choice was assessed under conditions in which waiting
      produced a continuously increasing probability of an outcome with a continuously
      decreasing magnitude (Experiment 1) or a continuously increasing magnitude of an
      outcome with a continuously decreasing probability (Experiment 2). Performance in
      both experiments reflected a greater desire for a higher probability even though
      the corresponding wait times produced substantive decreases in overall
      performance. These tendencies are considered to principally reflect hyperbolic
      discounting of probability, power discounting of magnitude, and the mathematical
      consequences of different response rates. Behavior in the CIRP is compared and
      contrasted with that in the Balloon Analogue Risk Task (BART). 

PMID- 24892659
TI  - New supramolecular assemblies in heterobimetallic chemistry: synthesis of a
      homologous series of unsolvated alkali-metal zincates.
AB  - Using an interlocking co-complexation approach, a homologous series of unsolvated
      alkali-metal zincates [MZn(CH2SiMe3)3] (M = Li 1, Na 2, K 3) was prepared by
      reacting equimolar amounts of Zn(CH2SiMe3)2 with the relevant alkali-metal alkyl
      M(CH2SiMe3) employing non-coordinating hexane as a solvent. X-ray
      crystallographic studies reveal that these heterobimetallic compounds exhibit
      unprecedented supramolecular assemblies made up exclusively of a three-fold
      combination of M-CH2, Zn-CH2 and M...Me interactions. Revealing an important
      alkali-metal effect, 1 displays a linear chain structure; whereas 2 and 3 form
      much more intricate 3D and 2D coordination networks respectively. Shedding new
      light into the formation of these solvent-free zincates, DFT calculations
      indicate that the infinite degree of aggregation observed in 1-3 plays a major
      role in thermodynamically driving the co-complexation reactions of their
      homometallic precursors. NMR spectroscopic studies suggest that in C6D6 solution
      1-3 exist as discrete contacted ion-pair species, where the alkali-metal is
      partially solvated by molecules of deuterated solvent. The supramolecular
      assemblies of 1-3 can be easily deaggregated by adding the polydentate N-donors
      PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) or TMEDA (N,N,N',N'
      tetramethylethylenediamine), affording monomeric [(PMDETA)LiZn(CH2SiMe3)3] (4)
      and [(TMEDA)2NaZn(CH2SiMe3)3] (5).

PMID- 24892660
TI  - The role of opportunistic migration in cyclic games.
AB  - We study cyclic evolutionary games in a spatial diluted grid environment in which
      agents strategically interact locally but can also opportunistically move to
      other positions within a given migration radius. We find that opportunistic
      migration can inverse the cyclic prevalence between the strategies when the
      frequency of random imitation is large enough compared to the payoff-driven
      imitation. At the transition the average size of the patterns diverges and this
      threatens diversity of strategies. 

PMID- 24892661
TI  - [Evaluation of the performance of Primary Health Care Services: experience in
      rural municipalities in Santander, Colombia].
AB  - OBJECTIVE: Public health services performance in Primary Health Care was
      evaluated in six municipalities from Santander, Colombia, after the development
      of a Primary Health Care program at the state level. METHODS: A cross-sectional,
      comparative study design was developed using a rapid assessment methodology,
      designed by Starfield. Patients, professionals and decision-makers were
      interviewed in three municipalities with higher development of the program and
      compared with three municipalities with lower development, all six predominantly
      rural areas. Propensity scores were calculate to equalize basal characteristics
      of groups being compared and multivariate analysis was used to evaluate the
      effect of the level of development of the program in the global performance index
      by patients. RESULTS: Higher total scores in the global performance index were
      found in patients in municipalities with higher development programs. Family
      focus, Community orientation and Access were dimensions with lower scores. Higher
      model development was associated with higher performance index scores by
      patients. CONCLUSIONS: In spite of higher primary health care model development
      was associated with best global performance scores, access, family focus and
      community orientation are attributes less developed.

PMID- 24892658
TI  - Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic
      behavior: a novel ex vivo and biophysical approach.
AB  - Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics
      systems; however, PCa may utilize the extensive innervation of the prostate for
      glandular egress. The interaction of PCa and its nerve fibers is observed in 80%
      of PCa and is termed perineural invasion (PNI). PCa cells have been observed
      traveling through the endoneurium of nerves, although the underlying mechanisms
      have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric
      transmembrane protein complexes comprised of a pore-forming alpha subunit and one
      or two auxiliary beta (beta) subunits with inherent cell adhesion molecule (CAM)
      functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs,
      while interacting putatively with other prominent neural CAMs. Furthermore, beta
      2 exhibits elevated mRNA and protein levels in highly metastatic and castrate
      resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta
      2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated
      behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI
      and subsequent PCa metastasis. The objective of this study was to determine the
      effect of beta-2 expression on PCa cell neurotropic metastasis associated
      behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan
      fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed
      neurotropic effects utilizing our novel ex vivo organotypic spinal cord co
      culture model, and performed functional assays with neural matrices and atomic
      force microscopy. With increased beta-2 expression, PCa cells display a trend of
      enhanced association with nerve axons. On laminin, a neural CAM, overexpression
      of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit
      marked binding affinity to laminin relative to LNECFP controls, and recombinant
      beta-2 ectodomain elicits more binding events to laminin than BSA control.
      Functional overexpression of VSSC beta subunits in PCa may mediate PCa metastatic
      behavior through association with neural matrices. 

PMID- 24892662
TI  - [Costs associated with nosocomial pneumonia in Universitary Hospital of Santander
      Colombia, 2007-2009].
AB  - OBJECTIVE: Estimate the excess of costs associated with nosocomial pneumonia not
      related to mechanical ventilation and clinical interventions that influence the
      cost. METHODS: A paired cohort study by time of occurrence of nosocomial event.
      The exposed groups were patients with nosocomial pneumonia and unexposed patients
      without this infection, whose diagnosis by the time of admission into the
      hospital was similar. The main outcome addressed was the direct costs of hospital
      care. RESULTS: Excess total cost of care associated to nosocomial pneumonia was
      col $ 7771583,50 (US $4 200, according to equivalence for year 2009). The costs
      related to intensive care unit explained 39 % of total costs (median col $
      2980000.00), antibiotics caused 33.7 % (median col $ 2571953,60) care in the
      general ward 19 % (median col $ 1473760,00), and daily medical visits 4.9 %
      (median col $ 379937,90). Other variables contributed about 1 % (such us X-ray,
      blood cultures, arterial blood gases, surgical procedures). CONCLUSIONS: We found
      that nosocomial pneumonia not associated with mechanical ventilation has a direct
      cost over col$ 7771583,50 (US $ 4 200 in 2009).

PMID- 24892663
TI  - [Concordance of two serological tests for the diagnosis of Chagas disease].
AB  - OBJECTIVE: Establish the concordance between in-house ELISA and IIF for the
      diagnosis of infection with T. cruzi using blood eluates. METHODOLOGY: A study of
      diagnostic technology evaluation and cross-sectional sample of 650 residents of
      an endemic area of Colombia was conducted. It was determined the Receiver
      Operating Characteristic curve (ROC) and IIF was used as a gold standard. It was
      established the cutoff for the ELISA and the correlation between readings.
      RESULTS: The in-house ELISA it was an agreement of 0.99 (95 % CI: 0.989 to 0.992)
      between the two readings taken and the area for the ROC curve was 0.9795. The
      cutoff was set at 0.5 absorbance in the ELISA test. 16.6 % were positive by ELISA
      and 10.9 % by IIF. CONCLUSIONS: The in-house ELISA showed good concordance
      compared to the IIF, so it is a good choice diagnostic for the population living
      in remote areas.

PMID- 24892664
TI  - [The effect of prescribing an unsupervised exercise program on the fitness
      profile of university students participating in an emergency response brigade].
AB  - OBJECTIVES: Determining the effect of a prescribed unsupervised exercise and
      counseling program on the physical activity and fitness levels of university
      students volunteering for an emergency response brigade. METHODOLOGY: Forty-two
      brigade volunteers engaged in a 12-week prescribed non-supervised exercise
      program. Body weight, body mass index (BMI), percentage body fat, waist
      circumference, oxygen consumption, flexibility and arms and abdomen strength
      endurance were assessed before and after performing the exercise program. The
      other variables measured concerned the level of physical activity during leisure
      time (days and minutes per week) and/or the use of alternative means of
      transport. Exercise was prescribed according to international standards. The
      activities, commitment and health-nutritional recommendations were controlled
      every two weeks. RESULTS: The study reported a statistically significant increase
      regarding the following variables: O2 consumption (from 46.41 +/- 6.65 ml/Kg/min
      to 47.70 +/- 6.27 ml/Kg/min; p<0.01), increased arm strength endurance (from
      11.82 +/- 9.97 to 14.74 +/- 12.74 repetitions; p<0.01) and an increase in the
      number of abdominal exercises (crunches) (from 21.16 +/- 11.91 to 26.64 +/- 17.03
      repeats; p<0.01). The real accomplishment regarding commitment by the time of the
      second measurement concerned 2.54 +/- 2.07 days/week and 144.16 +/- 238.89
      minutes/week of physical activity. These levels were significantly lower than
      those established at the beginning of the program (4 +/- 1.05 days/week and
      239.52 +/- 73.01 minutes/week; p<0.01). CONCLUSIONS: The prescribed unsupervised
      exercise and counseling program led to increases in oxygen consumption, arm
      strength endurance and the number of repeat abdominal crunches. Real fulfilment
      of the proposed activities was lower than planned original commitment.

PMID- 24892665
TI  - [Validation for Colombia of the CRAFFT substance abuse screening test in
      adolescents].
AB  - OBJECTIVES: Evaluate the properties of CRAFFT scale for substance abuse screening
      in adolescent population aged 14 to 18. METHODS: The criteria was validated by
      comparing the CRAFFT scale to the gold standard for substance use identification
      (i.e. the clinical interview). The diagnostic test model was used for calculating
      the sensitivity, specificity and predictive values of the scale. RESULTS: The
      test revealed 0.95 sensitivity, 0.83 specificity, 0.85 PPV and 0.94 NPV
      (chi(2)=187.87 and p<0.0005) for identifying dysfunctional use (frequent use,
      abuse and dependence) with a score >2. CONCLUSIONS: The scale was seen to have
      great usefulness for psychoactive substance use screening. A cut-off point of 2
      differentiated functional from dysfunctional use.

PMID- 24892667
TI  - [Quantifying polycyclic aromatic hydrocarbons in urine samples taken from traffic
      police working in Bogota's metropolitan area].
AB  - OBJECTIVE: Quantifying polycyclic aromatic hydrocarbon levels in urine samples
      taken from a population of traffic police working in the metropolitan area of
      Bogota who were occupationally exposed to 1-hydroxypyrene (1-OHP) and 3-hydroxy
      benzo[a]pyrene (3-BaP) metabolites from polycyclic aromatic hydrocarbons (PAH)
      having toxicological interest, related to their detection, and a degree of
      exposure to particulate material having a size less than 10 micrometres (PM10)
      and/or other factors. METHODS: A cross-sectional study was made of 524 traffic
      police, 413 of whom were engaged in operational and 111 in administrative
      functions. Urine samples were taken from all the individuals included in the
      study for determining PAH metabolites by gas chromatography/mass spectrometry
      (GC/MS). The presence of factors associated with the detection of metabolites was
      analysed, such as smoking, consuming roasted/grilled food, place of residence and
      exposure to PM10. The odds ratio (OR) was calculated as a measure of association.
      RESULTS: Higher 1-OHP and 3-BaP levels were found in exposed individuals, having
      a significant OR for detecting 6.3 ((3.6-11.1) 95 % CI) and 15.6 ((6.2-39) 95 %
      CI) metabolites, respectively. Significant OR were found for detecting PAH
      metabolites and exposure to PM10, smoking and consuming roasted/grilled food.
      DISCUSSION: There was an important and significant association between work
      related exposure to environmental contamination and detecting toxicologically
      important PAH metabolites in urine samples. Factors such as smoking, consuming
      freshly grilled/roasted food and exposure to PM10 were also found to be
      positively associated with detecting such metabolites, but to a lesser extent.

PMID- 24892666
TI  - [Dengue vector control using ether fractions from two plants (Asteraceae) as
      larvicide].
AB  - OBJECTIVE: Evaluating the larvicidal activity of two ether factions from
      Asteraceae (the aster, daisy or sunflower family, i.e. Heli opsisoppositifolia
      (L.) Druce (oxeye, sunflower-like) and Jaegeria hirta (Lag.) Less (weed-like)) on
      Aedes (Stegomyia) aegypti (L.) final third instar or initial fourth instar larvae
      near the town of Armenia in the Quindio Department in Colombia. METHODS: H.
      oppositifolia and J. hirta plants were collected and submitted to phytochemical
      analysis. Ether fractions were prepared form both species to assess 11
      concentrations for determining LC50, LC90 and LC95 lethal concentrations after 24
      and 48 h. The LC50, LC90 and LC95 results were used to create a mathematical
      model for describing lethal population-concentration dynamics. RESULTS:
      Phytochemical analysis identified tannins, flavonoids, quinones, cardiac
      glycosides, sterols, lactones, terpenes, courmarins and alkaloids in H.
      oppositifolia and J. hirta. LC after 48 h regarding J. hirta (LC50 24, LC90 70
      and LC95 93 ppm) was lower than those for H. oppositifolia (LC50 39, LC90 77 and
      LC95 94 ppm). A factorial ANOVA test confirmed this trend: 66 %, F=18.5 and
      p<0.05 for J. hirta and 34 %, F=18.5 and p<0.05 for H. oppositifolia. The
      mathematical simulation model suggested that using LC50 every 15 days and LC90
      and LC95 every 30 days from either of these species led to the same response
      compared to using LC90 and LC95 every 30 days or LC50 every 15 days. CONCLUSION:
      Both species had a larvicidal effect. However, J. Hirta turned out to be more
      promising as an eventual bioinsecticide for controlling A. Aegypti immature
      states.

PMID- 24892668
TI  - [Intimate partner violence in the Quindio, Department of Colombia].
AB  - OBJECTIVE: Identify risk factors for intimate partner violence by analyzing data
      from the surveillance system to domestic violence (SIVIF) in Quindio, 2009.
      MATERIALS AND METHODS: We conducted a cross- sectional descriptive study, about
      1,906 notifications SIVIF database in the department of Quindio, Colombia, in
      2009, of which 583 (n=583) correspond to cases where the independent of marital
      relationship between the victim-offender was married, a number that was taken as
      sample size, analyzing 100 % of such cases as to the origin, receipt of
      notification, type of coexistence of the couple, circumstances through aggression
      also features assaulted/aggressor. RESULTS: The two main municipalities generated
      most cases. Women, the most abused. More common types of physical violence,
      multiple sexual aggression with the body of the offender, the influence of anger,
      alcohol and drugs, jealousy, and emotional and psychological problems, the people
      attacked and attackers <= 35 years; battered women housewives and informal
      psychological violence, verbal or gross negligence and women >= 35 years so
      repeatedly assaulted, and who were not living in the same residence nor were
      married. CONCLUSIONS: There are many studies on the subject, even unprecedented
      in the region and in the national literature. It is imperative for the department
      of Quindio, further studies have to extend the present. Dating violence in
      Quindio, is a purely social phenomenon with chronicity of the city, marked by
      physical, sexual or multiple, with victims young women, more common in people
      with higher education, although the elderly were more often victimized so
      psychological, verbal and gross negligence.

PMID- 24892669
TI  - [An analysis of the updating of the Colombian social security system's mandatory
      health plan, 2009-2012].
AB  - OBJECTIVE: Analyzing the updating the Colombian social security system's
      mandatory health plan (MHP),from a perspective of the right to health, by
      comparing and contrasting MHP content valid until 31st December 2009 (POS-2009)
      with MHP content from 1st January 2012 onwards (POS-2012). METHODOLOGY: This was
      a descriptive study aimed at ascertaining the quantitative changes made and
      comparing the characteristics of modifications made in POS-2012 to POS-2009.
      RESULTS: Variation was observed between the two versions of the MHP regarding the
      number and characteristics of services and drugs;1,724 new procedures and 128 new
      medicines were included in the 2012 MHP, while 366 procedures and 79 medicines
      present in the 2009 MHP were excluded from MHP 2012. Some inclusions were related
      to frequent writs being issued from 2009-2011 demanding access to such procedures
      and drugs. DISCUSSION AND CONCLUSIONS: Significant progress was found regarding
      the content of the 2012 MHP compared to 2009 provision, thereby addressing some
      of the population's most frequent writs and plaints.

PMID- 24892670
TI  - [Respiratory tract infections in indigenous migrant Mexican day-laboring
      families' children].
AB  - OBJECTIVE: Identifying factors associated with respiratory tract infection in
      indigenous migrant day-laborer families'children living in the sugarcane sector
      in Colima, Mexico. METHODS: This was a cross-sectional study. Having given their
      informed consent, 71 mothers were interviewed for compiling pertinent
      sociodemographic data and a history of respiratory tract infection in their
      children during the harvest period 2010-2011. Anthropometry for 176 children aged
      0-14 years was recorded and they were clinically examined for upper and lower
      respiratory tract infection. Frequencies, percentages, Chi-square, odds ratio
      (crude and adjusted) and 95 % confidence intervals were calculated for the
      resulting data. RESULTS: 52.3 % of the children in the sample had a history of
      respiratory infection occurring during the last six months. Respiratory infection
      rates were statistically significant regarding temporary residence in
      shelters/hostels. The factors associated with a background of infection were
      being aged less than four years (AOR 4.06 (2.03-8.09) 95 % CI) and having been
      involved in temporary residence in a shelter,thereby leading to more overcrowding
      and an increased use of wood stoves for cooking (AOR 1.92 (1.01-3.63) 95 % CI).
      CONCLUSION: Indigenous migrant day-laboring families'children are vulnerable to
      respiratory infection. Prevention programs should target their activities by age
      group, emphasizing younger children, and promote improved sanitary conditions in
      the shelters.

PMID- 24892671
TI  - [The menarche and its impact on schoolgirls' physical qualities].
AB  - OBJECTIVES: Ascertaining the age when the menarche occurs in school girls living
      in Angra dos Reis/RJ and the pattern of physical qualities in periods during
      puberty using the menarche as the benchmark for sexual maturation. METHODS: The
      sample consisted of 232 10-to 16-year-old girls, divided into four groups
      according to sexual maturation. Following an interview during which the onset of
      the menarche was recalled, motor tests were scheduled for assessing physical
      qualities, lower limb power, running speed, flexibility and relative and absolute
      maximum oxygen consumption. Descriptive statistics were used for assessing the
      age of onset of the menarche; one-way ANOVA and Pearson's coefficient of
      correlation (p<0.05) were used for analyzing the physical qualities' pattern
      according to the onset of the menarche. RESULTS: The onset of the menarche was
      set at 12.23 +/- 1.2 years; significant differences were found regarding lower
      limb power, running speed, absolute and relative maximum oxygen consumption.
      CONCLUSIONS: The occurrence of the onset of the menarche agreed with other
      studies carried out in Brazil. Lower limb power and running speed were seen to
      increase during puberty, absolute maximum oxygen consumption increased (tending
      to decline two years after the menarche) and relative oxygen consumption
      decreased.

PMID- 24892672
TI  - [Genotoxicity in human lymphocytes exposed to PM10 from three sites in the Valle
      de Aburra (Antioquia)].
AB  - OBJECTIVE: Assessing air quality by determining PM(10) genotoxicity in human
      lymphocytes at three locations in the Valle de Aburra (Antioquia department).
      METHODS: Three sites were chosen in the Valle de Aburra (Barbosa, Corantioquia
      and the School of Mines) using Colombian reference (50 g/m3) and PM(10) content
      values, having annual low (25 mg /m3), medium (44 ug/m3) and high PM(10) average
      (91 ug/m3). PM10filters were analyzed during three different seasons between 2011
      and 2012: rainy, transitional and dry. Human lymphocytes were treated with the
      organic extract obtained from each filter to evaluate DNA damage using an
      alkaline comet assay. RESULTS: Genotoxicity was found to be highly significant
      (p<0.001) in all cases, compared to the negative control. The highest damage (six
      times) was seen in material from the School of Mines and during the transitional
      period. Differences were found between material from Barbosa and Corantioquia
      regarding that from the School of Mines concerning the induction of damage.
      CONCLUSIONS: Although the PM10 values reported for Barbosa and Corantioquia were
      below the maximum permitted level, genotoxic activity was found for PM10f rom
      both sites as well as for the School of Mines. These results show that physical
      chemical monitoring of particulate matter is not enough for assessing the exposed
      population's relative risk. Such analysis should thus be accompanied by using
      genotoxicity biomarkers, such as the comet assay.

PMID- 24892673
TI  - [Prevention of the onset of cigarette smoking in school: a critical approach to
      school-based studies].
AB  - This article explores the effectiveness of preventive interventions to smoking
      initiation in adolescents in school environment; it shows relevant aspects that
      account for the success or failure of those interventions and provides to
      professionals interested in the topic a selection of preventive strategies based
      on scientific evidence with the greatest impact when they are applied. It is
      concluded that the effectiveness of prevention programs on cigarette smoking
      initiation is partial and limited, because other interventions such as regulation
      of smoke-free areas, high price or control of sale and distribution are as
      important as the direct action on the new potential smokers. 

PMID- 24892674
TI  - Down-regulation of mir-221 and mir-222 restrain prostate cancer cell
      proliferation and migration that is partly mediated by activation of SIRT1.
AB  - Studies have shown that miR-221 and miR-222 are deregulated in many cancers,
      including prostate cancer. Nevertheless, the biological role and the underlying
      mechanisms of miR-221 and miR-222 in the pathogenesis of androgen-independent
      prostate cancer are still not clear. The proliferation, apoptosis, cell cycle
      distinction, and migration capacity of prostate cells were determined following
      transfection of miR-221 or miR-222 inhibitor. The biological impact and
      regulation of SIRT1 on prostate cancer cells were investigated. MiR-221 and miR
      222 were highly expressed in PC-3 cells compared with in LNCap cells. After miR
      221 or miR-222 expression was inhibited, the proliferation and migration rates of
      PC-3 cells decreased and the apoptosis rate increased. Moreover, SIRT1 protein
      was up-regulated in cells after they were transfected with miR-221 or miR-222
      inhibitor. Cells transfected with siSIRT1 showed increased migration and a
      decreased apoptosis rate, but there was no significant effect on cell
      proliferation compared with the controls. There was a negative correlation
      between miR-221 or miR-222 and SIRT1, but no direct target relationship was
      identified. These data demonstrate that miR-221 and miR-222 are highly expressed
      in PC-3 cells. Their inhibition leads to reduced cell proliferation and migration
      and increased apoptosis in prostate cancer cells. These effects are potentially
      mediated by up-regulation of SIRT1. 

PMID- 24892675
TI  - Independent of their localization in protein the hydrophobic amino acid residues
      have no effect on the molten globule state of apomyoglobin and the disulfide bond
      on the surface of apomyoglobin stabilizes this intermediate state.
AB  - At present it is unclear which interactions in proteins reveal the presence of
      intermediate states, their stability and formation rate. In this study, we have
      investigated the effect of substitutions of hydrophobic amino acid residues in
      the hydrophobic core of protein and on its surface on a molten globule type
      intermediate state of apomyoglobin. It has been found that independent of their
      localization in protein, substitutions of hydrophobic amino acid residues do not
      affect the stability of the molten globule state of apomyoglobin. It has been
      shown also that introduction of a disulfide bond on the protein surface can
      stabilize the molten globule state. However in the case of apomyoglobin,
      stabilization of the intermediate state leads to relative destabilization of the
      native state of apomyoglobin. The result obtained allows us not only to conclude
      which mutations can have an effect on the intermediate state of the molten
      globule type, but also explains why the introduction of a disulfide bond (which
      seems to "strengthen" the protein) can result in destabilization of the protein
      native state of apomyoglobin. 

PMID- 24892676
TI  - Site fidelity and individual variation in winter location in partially migratory
      European shags.
AB  - In partially migratory populations, individuals from a single breeding area
      experience a range of environments during the non-breeding season. If individuals
      show high within- and among- year fidelity to specific locations, any annual
      environmental effect on individual life histories could be reinforced, causing
      substantial demographic heterogeneity. Quantifying within- and among- individual
      variation and repeatability in non-breeding season location is therefore key to
      predicting broad-scale environmental impacts on the dynamics of partially
      migratory populations. We used field resightings of colour-ringed adult European
      shags known to have bred on the Isle of May, Scotland, to quantify individual
      variation and repeatability in winter location within and among three consecutive
      winters. In total, 3797 resightings of 882 individuals were recorded over 622 km
      of coastline, including the Isle of May. These individuals comprised over 50% of
      the known breeding population, and encompassed representative distributions of
      ages and sexes. The distances from the Isle of May at which individuals were
      resighted during winter varied substantially, up to 486 km and 136 km north and
      south respectively and including the breeding colony on the Isle of May. However,
      resighting distances were highly repeatable within individuals; within- and among
      winter repeatabilities were >0.72 and >0.59 respectively across the full
      September-March observation period, and >0.95 and >0.79 respectively across more
      restricted mid-winter periods. Repeatability did not differ significantly between
      males and females or among different age classes, either within or among winters.
      These data demonstrate that the focal shag population is partially migratory, and
      moreover that individuals show highly repeatable variation in winter location and
      hence migration strategy across consecutive winters. Such high among-individual
      variation and within-individual repeatability, both within and among winters,
      could lead to substantial life history variation, and therefore influence
      population dynamics and future conservation management strategies. 

PMID- 24892678
TI  - Observation of strain-free rolled-up CVD graphene single layers: toward
      unstrained heterostructures.
AB  - Single layer graphene foils produced by chemical vapor deposition (CVD) are
      rolled with self-positioned layers of InGaAs/Cr forming compact multi-turn
      tubular structures that consist on successive graphene/metal/semiconductor
      heterojunctions on a radial superlattice. Using elasticity theory and Raman
      spectroscopy, we show that it is possible to produce homogeneously curved
      graphene with a curvature radius on the 600-1200 nm range. Additionally, the
      study of tubular structures also allows the extraction of values for the elastic
      constants of graphene that are in excellent agreement with elastic constants
      found in the literature. However, our process has the advantage of leading to a
      well-defined and nonlocal curvature. Since our curvature radius lies in a range
      between the large radius studied using mechanical bending and the reduced radius
      induced by atomic force microscopy experiments, we can figure out whether bending
      effects can be a majoritary driving force for modifications in graphene
      electronic status. From the results described in this work, one can assume that
      curvature effects solely do not modify the Raman signature of graphene and that
      strain phenomena observed previously may be ascribed to possible stretching due
      to the formation of local atomic bonds. This implies that the interactions of
      graphene with additional materials on heterostructures must be investigated in
      detail prior to the development of applications and devices. 

PMID- 24892677
TI  - How the malaria vector Anopheles gambiae adapts to the use of insecticide-treated
      nets by African populations.
AB  - BACKGROUND: Insecticide treated bed nets have been recommended and proven
      efficient as a measure to protect African populations from malaria mosquito
      vector Anopheles spp. This study evaluates the consequences of bed nets use on
      vectors resistance to insecticides, their feeding behavior and malaria
      transmission in Dielmo village, Senegal, were LLINs were offered to all villagers
      in July 2008. METHODS: Adult mosquitoes were collected monthly from January 2006
      to December 2011 by human landing catches (HLC) and by pyrethroid spray catches
      (PCS). A randomly selected sub-sample of 15-20% of An. gambiae s.l. collected
      each month was used to investigate the molecular forms of the An. gambiae
      complex, kdr mutations, and Plasmodium falciparum circumsporozoite (CSP) rate.
      Malaria prevalence and gametocytaemia in Dielmo villagers were measured
      quarterly. RESULTS: Insecticide susceptible mosquitoes (wild kdr genotype)
      presented a reduced lifespan after LLINs implementation but they rapidly adapted
      their feeding behavior, becoming more exophageous and zoophilic, and biting
      earlier during the night. In the meantime, insecticide-resistant specimens (kdr
      L1014F genotype) increased in frequency in the population, with an unchanged
      lifespan and feeding behaviour. P. falciparum prevalence and gametocyte rate in
      villagers decreased dramatically after LLINs deployment. Malaria infection rate
      tended to zero in susceptible mosquitoes whereas the infection rate increased
      markedly in the kdr homozygote mosquitoes. CONCLUSION: Dramatic changes in vector
      populations and their behavior occurred after the deployment of LLINs due to the
      extraordinary adaptative skills of An. gambiae s. l. mosquitoes. However, despite
      the increasing proportion of insecticide resistant mosquitoes and their almost
      exclusive responsibility in malaria transmission, the P. falciparum gametocyte
      reservoir continued to decrease three years after the deployment of LLINs.

PMID- 24892680
TI  - Crural amputation of a newborn as a consequence of intraosseous needle insertion
      and calcium infusion.
AB  - Intraosseous needle insertion and infusion is considered an easy and reliable
      method of achieving a vascular access in acute circulatory collapse where other
      methods have not been successful within reasonable time. Complications are
      considered few but may be serious. We present a case of a newborn girl, where
      intraosseous cannulation of the tibia was lifesaving. Despite following most
      standard recommendations, the treatment resulted in transtibial amputation due to
      necrosis. We suspect that the necrosis was a consequence of extravasation of
      tissue-toxic calcium infusion. 

PMID- 24892681
TI  - Life-threatening pneumonitis complicating low-dose methotrexate treatment for
      juvenile idiopathic arthritis in a child.
AB  - Methotrexate, a drug commonly used to treat juvenile idiopathic arthritis (JIA),
      has been reported to cause interstitial pneumonitis as a rare complication in
      adults with rheumatoid arthritis. Only 1 suspicious case of methotrexate
      pneumonitis in a child with JIA has been reported in 1998, though with no
      histopathologic proof. Given its rarity and nonspecific presenting symptoms,
      diagnosis may be challenging, and a life-threatening illness can occur without a
      high index of suspicion, as illustrated by this report of a 13-year-old girl with
      JIA who developed fever, nonproductive cough, and dyspnea as presenting features
      of interstitial pneumonitis after 1 year of methotrexate therapy. Chest high
      resolution computed tomography revealed patchy ground-glass opacities and
      interlobular septal thickening without pleural effusion. Lung biopsy showed
      interstitial pneumonitis with diffuse alveolar damage. The symptoms and
      radiographs improved dramatically after withdrawal of methotrexate and
      administration of corticosteroids. A restrictive ventilatory defect with
      decreased diffusion capacity on pulmonary function testing persisted until 20
      months after methotrexate withdrawal. There is no single pathognomic feature for
      methotrexate pneumonitis; rather, diagnosis relies on a constellation of
      clinical, radiologic, and pathologic findings. This report highlights the
      necessity for pediatricians to be continuously vigilant for interstitial
      pneumonitis in children receiving methotrexate who develop new unexplained
      pulmonary symptoms. 

PMID- 24892682
TI  - Hemoperitoneum: an unusual presentation of chronic granulocytic leukemia in a
      pediatric patient.
AB  - Chronic granulocytic leukemia (CGL) is a rare hematologic disease in pediatric
      patients. It usually presents with insidious symptoms. However, some cases may
      have an atypical presentation. We report herein the case of a 13-year-old female
      admitted to the emergency department with acute abdomen. She had
      hyperleukocytosis of 500.0 * 1000 cells/mm suggestive of CGL. A paracentesis was
      performed due to abdominal compartment syndrome that demonstrated hemoperitoneum.
      At laparotomy, a ruptured ovarian mass was found with multiple tumor implants in
      the serosal surface. Pathology revealed a CGL-infiltrated ovary. The patient is
      currently stable, has finished adjuvant chemotherapy, and is at 24 months of
      follow-up. To our knowledge, this is the first report of such a case. 

PMID- 24892683
TI  - A rare case of penetrating brain injury by crossbow in a 22-month-old child.
AB  - Nonmissile penetrating brain injuries are exceedingly uncommon among civilian
      population and are most often associated with inflicted injury. They show
      specific characteristics different from that of missile wounds. In this article,
      we describe a rare case of a 22-month-old child who experienced accidental
      penetrating head trauma caused by a crossbow. We document neuroimaging studies
      and review the management concerning this pathology. To our knowledge, this is
      the youngest survived case of penetrating brain injury by a crossbow with such
      radiological findings reported in the literature. 

PMID- 24892684
TI  - A rare presentation of seizures in a not-so-rare disease: Henoch-Schonlein
      purpura presenting with repeated seizures.
AB  - Henoch-Schonlein purpura represents the most common form of systemic vasculitis
      in children. Although a very common cause of vasculitis, seizures are a very rare
      complication of this disorder. We report a 5-year-old boy who presents with no
      other clinical symptoms of the disorder other than a seizure. By presenting this
      case, we hope to expand the differential diagnosis of repeated seizures to
      include diseases in which the pathogenesis of diseases with small vessel
      vasculitis such as Henoch-Schonlein purpura is considered. 

PMID- 24892685
TI  - Review of the use of lipid emulsion in nonlocal anesthetic poisoning.
AB  - Intravenous lipid emulsion (ILE) has been used widely for the treatment of
      poisoning due to local anesthetic agent and is increasingly reported as a therapy
      for other forms of poisoning. This article will review the proposed mechanisms of
      action for ILE in poisoning and the evidence from animal studies and human
      experience supporting the use of ILE for poisoning due to nonlocal anesthetic
      agents. 

PMID- 24892687
TI  - Botfly larva masquerading as periorbital cellulitis: identification by point-of
      care ultrasonography.
AB  - Myiasis, or the infiltration of the botfly larvae, is a relatively frequent
      problem encountered by travelers to parts of Latin America. This is a novel case
      report that documents a Dermatobia hominis infestation of the left facial region
      with secondary periorbital cellulitis diagnosed by point-of-care ultrasonography.

PMID- 24892688
TI  - Pediatric emergency medicine: legal briefs.

PMID- 24892689
TI  - Pallor and lethargy in a 19-month-old boy.

PMID- 24892690
TI  - ECGs in the ED.

PMID- 24892691
TI  - Data for disaster planning: risk factors for internal radiation exposures after
      Fukushima.

PMID- 24892692
TI  - 4'-carboxy-7-hydroxyflavylium. A multistate system involving twelve species
      reversibly interconverted by pH and light stimuli.
AB  - In the frame of the metamorphosis chemistry, where complexity is achieved at the
      bottom, a multistate system based on 4'-carboxy-7-hydroxyflavylium is described.
      Twelve species reversibly interconverted by pH and light stimuli were identified
      at the equilibrium or as transients. The carboxylic substituent deprotonates at
      moderately acidic pH values and as a consequence allows the existence of two
      photoactive trans-chalcones, whose irradiation leads to different photoproducts.
      The thermodynamic and kinetic properties of the network of reactions of the
      multistate system were investigated by means of UV-vis spectroscopy, stopped
      flow, continuous irradiation, and flash photolysis. The evolution of the system
      to the equilibrium when the pH is raised from acidic to higher pH values can take
      place through two different routes involving the protonated or the deprotonated
      species at the carboxylic acid substituent. The kinetics and the photochromism of
      the system were rationalized by means of an energy level diagram. 

PMID- 24892693
TI  - In vitro selection of DNA aptamers for metastatic breast cancer cell recognition
      and tissue imaging.
AB  - Cancer is a major public health issue, with metastatic cancer accounting for the
      overwhelming majority of cancer deaths. Early diagnosis and appropriate treatment
      of metastatic cancer may largely prolong the survival rate and improve the
      quality of life for patients. In this study, we have identified a panel of DNA
      aptamers specifically binding to MDA-MB-231 cells derived from metastatic site
      pleural effusion, with high affinity after 15 rounds of selections using the cell
      based systematic evolution of ligands by exponential enrichment (SELEX) method.
      The selected aptamers were subjected to flow cytometry and laser confocal
      fluorescence microscopy to evaluate their binding affinity and selectivity. The
      aptamer LXL-1 with the highest abundance in the enriched library demonstrated a
      low K(d) value and excellent selectivity for the recognition of the metastatic
      breast cancer cells. Tissue imaging results showed that truncated aptamer
      sequence LXL-1-A was highly specific to the corresponding tumor tissue and
      displayed 76% detection rate against breast cancer tissue with metastasis in
      regional lymph nodes. Therefore, on the basis of its excellent targeting
      properties and functional versatility, LXL-1-A holds great potential to be used
      as a molecular imaging probe for the detection of breast cancer metastasis. Our
      result clearly demonstrates that metastatic-cell-based SELEX can be used to
      generate DNA ligands specifically recognizing metastatic cancer cells, which is
      of great significance for metastatic cancer diagnosis and treatment.

PMID- 24892694
TI  - HIV treatment-as-prevention research at a crossroads.

PMID- 24892695
TI  - Noninvasive technique for the diagnosis of patent ductus arteriosus in premature
      infants by analyzing pulse wave phases on photoplethysmography signals measured
      in the right hand and the left foot.
AB  - OBJECTIVE: To evaluate the impact of patent ductus arteriosus (PDA) on the pulse
      phase difference (PPD) between the left foot (postductal region) and the right
      hand (preductal region). MATERIALS AND METHODS: PPD was determined from arterial
      photoplethysmography signals (pulse waves) measured by infrared sensors routinely
      used for pulse oximetry in 56 premature infants less than 32 weeks gestation.
      Only infants with significant PDA (sPDA) diagnosed by echocardiography were
      treated with ibuprofen (for 3 days). Patients were classified according to
      whether or not they responded (Success/Failure) to this treatment. The Control
      group was composed of infants in whom ductus had already closed spontaneously at
      the time of the first echocardiography. The 3 groups were compared in terms of
      PPD at the beginning (T1) and at the end (T2) of the study. For patients in the
      Failure (n = 17) and Success groups (n = 18), T1 corresponded to the first day of
      treatment and T2 to the day after completion of the course of ibuprofen. In the
      Control group (n = 21), T1 corresponded to 1 to 3 days of life (DOL), and T2 to 4
      6 DOL. RESULTS: Compared to the Control group, PPD was higher in the Failure (at
      T1 and T2) and Success (at T1) groups characterized by sPDA. After ibuprofen
      therapy, PPD in the Success group decreased to about the level observed in the
      Control group. The area under the ROC curve of PPD for the diagnosis of sPDA was
      0.98 (95% CI 0.96-1); for an optimal cut-off of PPD >= 1.65 deg/cm, the
      sensitivity was 94.2% and the specificity was 98.3%. CONCLUSION: In this study,
      PPD was correlated with ductus arteriosus status evaluated by echocardiography,
      indicating involvement of the ductal shunt in the mechanism of redistribution in
      systemic vascular territories. PPD can be considered for the diagnosis of
      hemodynamically significant PDA.

PMID- 24892696
TI  - Lack of BCG vaccination and other risk factors for bacteraemia in severely
      malnourished children with pneumonia.
AB  - We sought to examine the factors associated with bacteraemia and their outcome in
      children with pneumonia and severe acute malnutrition (SAM). All SAM children of
      either sex, aged 0-59 months, admitted to the Dhaka Hospital of the International
      Centre for Diarrhoeal Disease Research, Bangladesh with radiologically confirmed
      pneumonia from April 2011 to July 2012 were enrolled (n = 405). Comparison was
      made between pneumonic SAM children with (cases = 18), and without (controls =
      387) bacteraemia. The death rate was significantly higher in cases than controls
      (28% vs. 8%, P < 0.01). In logistic regression analysis, after adjusting for
      potential confounders, the SAM children with pneumonia and bacteraemia more often
      had a history of lack of bacillus Calmette-Guerin (BCG) vaccination (odds ratio
      7.39, 95% confidence interval 1.67-32.73, P < 0.01). The results indicate the
      importance of continuation of BCG vaccination which may provide benefit beyond
      its primary purpose.

PMID- 24892697
TI  - Recognition of TLR2 N-glycans: critical role in ArtinM immunomodulatory activity.
AB  - TLR2 plays a critical role in the protection against Paracoccidioides
      brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding
      lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and
      dendritic cells, which accounts for the T helper1 immunity that results from
      ArtinM administration. We examined the direct interaction of ArtinM with
      TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1
      or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF
      kappaB activation and interleukin (IL)-8 production in cells transfected with
      TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had
      augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated
      macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In
      addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that
      had been captured by specific antibodies from a macrophages lysate.
      Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre
      incubated with mannotriose. The biological relevance of the direct interaction of
      ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which
      produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than
      macrophages from wild-type mice. Pre-treatment of murine macrophages with
      pharmacological inhibitors of signaling molecules demonstrated the involvement of
      p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement
      ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2
      heterodimers in a carbohydrate recognition-dependent manner and functions as a
      TLR2 agonist with immunomodulatory properties. 

PMID- 24892699
TI  - Antibody modified porous silicon microparticles for the selective capture of
      cells.
AB  - Herein, the ability of porous silicon (PSi) particles for selectively binding to
      specific cells is investigated. PSi microparticles with a high reflectance band
      in the reflectivity profile are fabricated, and subsequently passivated and
      modified with antibodies via the Cu(I)-catalyzed alkyne-azide cycloaddition
      reaction and succimidyl activation. To demonstrate the ability of the antibody
      modified PSi particles to selectively bind to one cell type over others, HeLa
      cells were transfected with surface epitopes fused to fluorescent proteins. The
      antibody-functionalized PSi particles showed good selectivity for the
      corresponding surface protein on HeLa cells, with no significant cross
      reactivity. The results are important for the application of PSi particles in
      cell sensing and drug delivery. 

PMID- 24892700
TI  - Sequential studies of silver released from silver nanoparticles in aqueous media
      simulating sweat, laundry detergent solutions and surface water.
AB  - From an increased use of silver nanoparticles (Ag NPs) as an antibacterial in
      consumer products follows a need to assess the environmental interaction and fate
      of their possible dispersion and release of silver. This study aims to elucidate
      an exposure scenario of the Ag NPs potentially released from, for example,
      impregnated clothing by assessing the release of silver and changes in particle
      properties in sequential contact with synthetic sweat, laundry detergent
      solutions, and freshwater, simulating a possible transport path through different
      aquatic media. The release of ionic silver is addressed from a water chemical
      perspective, compared with important particle and surface characteristics.
      Released amounts of silver in the sequential exposures were significantly lower,
      approximately a factor of 2, than the sum of each separate exposure. Particle
      characteristics such as speciation (both of Ag ionic species and at the Ag NP
      surface) influenced the release of soluble silver species present on the surface,
      thereby increasing the total silver release in the separate exposures compared
      with sequential immersions. The particle stability had no drastic impact on the
      silver release as most of the Ag NPs were unstable in solution. The silver
      release was also influenced by a lower pH (increased release of silver), and
      cotransported zeolites (reduced silver in solution). 

PMID- 24892698
TI  - Deficiency of the transcriptional repressor B cell lymphoma 6 (Bcl6) is
      accompanied by dysregulated lipid metabolism.
AB  - The transcriptional repressor B-cell Lymphoma 6 (Bcl6) was recently identified in
      a profile of genes regulated in adipocytes, suggesting a relationship between
      Bcl6 and metabolic regulation. As a representative target gene repressed by Bcl6,
      Suppressor of Cytokine Signaling (Socs) 2 expression was elevated in Bcl6
      deficient (KO) mice, including metabolic tissues liver, adipose tissue and
      muscle, as well as in spleen and thymus. Bcl6 occupied the Socs2 promoter in wild
      type, but not Bcl6 KO mice, suggesting direct regulation of Socs2 by Bcl6 in
      vivo. Mice deficient in Bcl6 were found to exhibit multiple features of
      dysregulated lipid metabolism. Adipose tissue mass was dramatically reduced or
      absent in Bcl6 KO mice. Further, hepatic and serum triglycerides were low. Bcl6
      deficiency was accompanied by decreased hepatic expression of Stearoyl-CoA
      desaturase 1 (Scd1) and Fatty acid synthase (Fasn) genes which encode lipogenic
      enzymes. Expression of the gene for the transcription factor Carbohydrate
      Responsive Element Binding Protein (Chrebp), which regulates expression of
      lipogenic genes, was also reduced in liver of Bcl6 KO mice. Bcl6 deficiency
      disrupted fasting-induced increases in hepatic triglyceride deposition, but not
      decreases in lipogenic gene expression. Taken together, these findings suggest
      that in addition to its well-recognized roles in immune regulation, Bcl6 plays a
      role in regulatory events of lipid metabolism, and that in the absence of Bcl6,
      lipid metabolism in liver and adipose tissue is dysregulated. 

PMID- 24892701
TI  - A conversation with P. Roy Vagelos. Interview by Ushma S. Neill.

PMID- 24892702
TI  - Kidney disease: new technologies translate mechanisms to cure.
AB  - Kidney disease is one of the most prevalent chronic conditions and is a frequent
      complication of diabetes, cardiovascular disease, and obesity. Recent advances in
      biomedical research and novel technologies have created opportunities to study
      kidney disease in a variety of platforms, applied to human populations. The
      Reviews in this series discuss the kidney in hypertension, diabetes, and
      monogenic forms of kidney disease, as well as the cellular and molecular
      mediators of acute kidney injury and fibrosis, IgA nephropathy and idiopathic
      membranous nephropathy, and kidney transplantation. In this introduction, we
      briefly review new insights into focal segmental glomerulosclerosis and the role
      of podocytes in health and disease. Additionally, we discuss how new
      technologies, therapeutics, and the availability of patient data can help shape
      the study of kidney disease and ultimately inform policies concerning biomedical
      research and health care. 

PMID- 24892703
TI  - Cellular and molecular mechanisms in kidney fibrosis.
AB  - Fibrosis is a characteristic feature of all forms of chronic kidney disease.
      Deposition of pathological matrix in the interstitial space and within the walls
      of glomerular capillaries as well as the cellular processes resulting in this
      deposition are increasingly recognized as important factors amplifying kidney
      injury and accelerating nephron demise. Recent insights into the cellular and
      molecular mechanisms of fibrogenesis herald the promise of new therapies to slow
      kidney disease progression. This review focuses on new findings that enhance
      understanding of cellular and molecular mechanisms of fibrosis, the
      characteristics of myofibroblasts, their progenitors, and molecular pathways
      regulating both fibrogenesis and its resolution. 

PMID- 24892704
TI  - Membranous nephropathy: from models to man.
AB  - As recently as 2002, most cases of primary membranous nephropathy (MN), a
      relatively common cause of nephrotic syndrome in adults, were considered
      idiopathic. We now recognize that MN is an organ-specific autoimmune disease in
      which circulating autoantibodies bind to an intrinsic antigen on glomerular
      podocytes and form deposits of immune complexes in situ in the glomerular
      capillary walls. Here we define the clinical and pathological features of MN and
      describe the experimental models that enabled the discovery of the major target
      antigen, the M-type phospholipase A2 receptor 1 (PLA2R). We review the
      pathophysiology of experimental MN and compare and contrast it with the human
      disease. We discuss the diagnostic value of serological testing for anti-PLA2R
      and tissue staining for the redistributed antigen, and their utility for
      differentiating between primary and secondary MN, and between recurrent MN after
      kidney transplant and de novo MN. We end with consideration of how knowledge of
      the antigen might direct future therapeutic strategies. 

PMID- 24892705
TI  - Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney
      disease.
AB  - Recent advances in defining the genetic mechanisms of disease causation and
      modification in autosomal dominant polycystic kidney disease (ADPKD) have helped
      to explain some extreme disease manifestations and other phenotypic variability.
      Studies of the ADPKD proteins, polycystin-1 and -2, and the development and
      characterization of animal models that better mimic the human disease, have also
      helped us to understand pathogenesis and facilitated treatment evaluation. In
      addition, an improved understanding of aberrant downstream pathways in ADPKD,
      such as proliferation/secretion-related signaling, energy metabolism, and
      activated macrophages, in which cAMP and calcium changes may play a role, is
      leading to the identification of therapeutic targets. Finally, results from
      recent and ongoing preclinical and clinical trials are greatly improving the
      prospects for available, effective ADPKD treatments. 

PMID- 24892707
TI  - Molecular mechanisms of diabetic kidney disease.
AB  - Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide
      and the single strongest predictor of mortality in patients with diabetes. DKD is
      a prototypical disease of gene and environmental interactions. Tight glucose
      control significantly decreases DKD incidence, indicating that hyperglycemia
      induced metabolic alterations, including changes in energy utilization and
      mitochondrial dysfunction, play critical roles in disease initiation. Blood
      pressure control, especially with medications that inhibit the angiotensin
      system, is the only effective way to slow disease progression. While DKD is
      considered a microvascular complication of diabetes, growing evidence indicates
      that podocyte loss and epithelial dysfunction play important roles. Inflammation,
      cell hypertrophy, and dedifferentiation by the activation of classic pathways of
      regeneration further contribute to disease progression. Concerted clinical and
      basic research efforts will be needed to understand DKD pathogenesis and to
      identify novel drug targets. 

PMID- 24892706
TI  - The genetics and immunobiology of IgA nephropathy.
AB  - IgA nephropathy (IgAN) represents the leading cause of kidney failure among East
      Asian populations and the most frequent form of primary glomerulonephritis among
      Europeans. Patients with IgAN develop characteristic IgA1-containing immune
      complexes that deposit in the glomerular mesangium, producing progressive kidney
      injury. Recent studies define IgAN as an autoimmune trait of complex architecture
      with a strong genetic determination. This Review summarizes new insights into the
      role of the O-glycosylation pathway, anti-glycan immune response, mucosal
      immunity, antigen processing and presentation, and the alternative complement
      pathway in the pathogenesis of IgAN. 

PMID- 24892708
TI  - The inextricable role of the kidney in hypertension.
AB  - An essential link between the kidney and blood pressure control has long been
      known. Here, we review evidence supporting the premise that an impaired capacity
      of the kidney to excrete sodium in response to elevated blood pressure is a major
      contributor to hypertension, irrespective of the initiating cause. In this
      regard, recent work suggests that novel pathways controlling key sodium
      transporters in kidney epithelia have a critical impact on hypertension
      pathogenesis, supporting a model in which impaired renal sodium excretion is a
      final common pathway through which vascular, neural, and inflammatory responses
      raise blood pressure. We also address recent findings calling into question long
      standing notions regarding the relationship between sodium intake and changes in
      body fluid volume. Expanded understanding of the role of the kidney as both a
      cause and target of hypertension highlights key aspects of pathophysiology and
      may lead to identification of new strategies for prevention and treatment. 

PMID- 24892709
TI  - Complement as a multifaceted modulator of kidney transplant injury.
AB  - Improvements in clinical care and immunosuppressive medications have positively
      affected outcomes following kidney transplantation, but graft survival remains
      suboptimal, with half-lives of approximately 11 years. Late graft loss results
      from a confluence of processes initiated by ischemia-reperfusion injury and
      compounded by effector mechanisms of uncontrolled alloreactive T cells and anti
      HLA antibodies. When combined with immunosuppressant toxicity, post-transplant
      diabetes and hypertension, and recurrent disease, among other factors, the result
      is interstitial fibrosis, tubular atrophy, and graft failure. Emerging evidence
      over the last decade unexpectedly identified the complement cascade as a common
      thread in this process. Complement activation and function affects allograft
      injury at essentially every step. These fundamental new insights, summarized
      herein, provide the foundation for testing the efficacy of various complement
      antagonists to improve kidney transplant function and long-term graft survival. 

PMID- 24892713
TI  - Retraction. The IL-12Rbeta2 gene functions as a tumor suppressor in human B cell
      malignancies.

PMID- 24892711
TI  - Inhibiting HDAC for human hematopoietic stem cell expansion.
AB  - In this issue of the JCI, Chaurasia and colleagues report an impressive ex vivo
      expansion of HSCs from human cord blood (CB) using cytokines and altering
      epigenetic modifications. The application of this protocol provides information
      that has potential for clinical consideration. The enhanced expansion of CB HSCs
      is a substantial advance over recent work from the Chaurasia and Hoffman group,
      in which ex vivo production of human erythroid progenitor cells from CB was
      promoted by chromatin modification. Moreover, this study takes advantage of
      information from the rapidly emerging, but not yet fully elucidated, field of
      epigenetics. 

PMID- 24892710
TI  - Therapeutic translation in acute kidney injury: the epithelial/endothelial axis.
AB  - Acute kidney injury (AKI) remains a major clinical event with rising incidence,
      severity, and cost; it now has a morbidity and mortality exceeding acute
      myocardial infarction. There is also a documented conversion to and acceleration
      of chronic kidney disease to end-stage renal disease. The multifactorial nature
      of AKI etiologies and pathophysiology and the lack of diagnostic techniques have
      hindered translation of preclinical success. An evolving understanding of
      epithelial, endothelial, and inflammatory cell interactions and individualization
      of care will result in the eventual development of effective therapeutic
      strategies. This review focuses on epithelial and endothelial injury mediators,
      interactions, and targets for therapy. 

PMID- 24892717
TI  - Mother-child emotion communication and childhood anxiety symptoms.
AB  - This study examined whether several aspects of emotion communication in mother
      child dyads relate to child anxiety symptoms. Mother and child behaviours related
      to emotion communication were coded based on videotaped mother-child interactions
      in a sample of 87 ten- to twelve-year olds, and children reported on their
      anxiety symptoms. Mothers of more anxious children were less supportive in that
      they engaged more in psychologically controlling behaviours designed to
      manipulate the child's emotional state, exhibited less warmth and interest in the
      child, and were less elaborative during conversations about an emotionally
      negative event. Further, more anxious children showed greater affect intensity
      and lower congruency of emotions and behaviours, and were less engaged in the
      conversation. Examining the role of child gender did not change the results
      significantly. Mother and child emotion communication behaviours each explained
      significant variance in child anxiety. The results showed that how mothers and
      children approached emotion-related conversations is important for child anxiety,
      and highlighted the need to consider mother and child behaviours related to
      emotion communication in assessment and interventions with anxious children. 

PMID- 24892712
TI  - Epac1-dependent phospholamban phosphorylation mediates the cardiac response to
      stresses.
AB  - PKA phosphorylates multiple molecules involved in calcium (Ca2+) handling in
      cardiac myocytes and is considered to be the predominant regulator of beta
      adrenergic receptor-mediated enhancement of cardiac contractility; however,
      recent identification of exchange protein activated by cAMP (EPAC), which is
      independently activated by cAMP, has challenged this paradigm. Mice lacking Epac1
      (Epac1 KO) exhibited decreased cardiac contractility with reduced phospholamban
      (PLN) phosphorylation at serine-16, the major PKA-mediated phosphorylation site.
      In Epac1 KO mice, intracellular Ca2+ storage and the magnitude of Ca2+ movement
      were decreased; however, PKA expression remained unchanged, and activation of PKA
      with isoproterenol improved cardiac contractility. In contrast, direct activation
      of EPAC in cardiomyocytes led to increased PLN phosphorylation at serine-16,
      which was dependent on PLC and PKCepsilon. Importantly, Epac1 deletion protected
      the heart from various stresses, while Epac2 deletion was not protective.
      Compared with WT mice, aortic banding induced a similar degree of cardiac
      hypertrophy in Epac1 KO; however, lack of Epac1 prevented subsequent cardiac
      dysfunction as a result of decreased cardiac myocyte apoptosis and fibrosis.
      Similarly, Epac1 KO animals showed resistance to isoproterenol- and aging-induced
      cardiomyopathy and attenuation of arrhythmogenic activity. These data support
      Epac1 as an important regulator of PKA-independent PLN phosphorylation and
      indicate that Epac1 regulates cardiac responsiveness to various stresses. 

PMID- 24892718
TI  - Routes of motivation: stable psychological dispositions are associated with
      dynamic changes in cortico-cortical functional connectivity.
AB  - The present study provides a neurobiological framework to the theory of epistemic
      motivation that has been extensively studied for the last three decades in the
      domain of social cognition. Epistemic motivations affect the way people generate
      and validate hypotheses, and ultimately form and modify knowledge. Strong
      dispositional measures such as need for cognitive closure (NCC), the desire for a
      quick firm answer (any answer) to a question, show gross and stable inter
      individual differences. The cognitive mechanisms and neural underpinnings of such
      differences, however, remain largely unexplored. Here we show that high (compared
      to low) levels of NCC, measured with need for cognitive closure scale, are
      associated with reduced online adjustment in cognitive control, as indexed by
      behavioral conflict adaptation. This behavioral effect is mediated by dynamic
      changes in cortico-cortical functional connectivity between prefrontal regions
      involved in conflict monitoring and implementation of cognitive control. In
      particular, these regions show increased functional connectivity after exposure
      to conflict in low but not high NCC individuals. These results demonstrate that
      the level of flexibility of functional cortico-cortical connections can mediate
      stable psychological dispositions. 

PMID- 24892719
TI  - Nanomechanical phenotype of chondroadherin-null murine articular cartilage.
AB  - Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP),
      was hypothesized to play important roles in regulating chondrocyte signaling and
      cartilage homeostasis. However, its roles in cartilage development and function
      are not well understood, and no major osteoarthritis-like phenotype was found in
      the murine model with CHAD genetically deleted (CHAD(-/-)). In this study, we
      used atomic force microscopy (AFM)-based nanoindentation to quantify the effects
      of CHAD deletion on changes in the biomechanical function of murine cartilage. In
      comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ~70
      80% reduction in the indentation modulus, Eind, of the superficial zone knee
      cartilage of 11 weeks, 4 months and 1 year old animals. This mechanical phenotype
      correlates well with observed increases in the heterogeneity collagen fibril
      diameters in the surface zone. The results suggest that CHAD mainly plays a major
      role in regulating the formation of the collagen fibrillar network during the
      early skeletal development. In contrast, CHAD-deletion had no appreciable effects
      on the indentation mechanics of middle/deep zone cartilage, likely due to the
      dominating role of aggrecan in the middle/deep zone. The presence of significant
      rate dependence of the indentation stiffness in both WT and CHAD(-/-) knee
      cartilage suggested the importance of both fluid flow induced poroelasticity and
      intrinsic viscoelasticity in murine cartilage biomechanical properties.
      Furthermore, the marked differences in the nanomechanical behavior of WT versus
      CHAD(-/-) cartilage contrasted sharply with the relative absence of overt
      differences in histological appearance. These observations highlight the
      sensitivity of nanomechanical tools in evaluating structural and mechanical
      phenotypes in transgenic mice.

PMID- 24892721
TI  - Resveratrol sensitizes HepG2 cells to TRAIL-induced apoptosis.
AB  - Resveratrol is a natural polyphenol found in a wide variety of plants, including
      grapes, berries, and peanuts. Resveratrol can modulate a wide spectrum of
      molecular targets, including those involved in cancer signaling pathways. Here,
      we evaluated the role of resveratrol in tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) and examined the molecular mechanisms in the human
      hepatocellular carcinoma cell line HepG2. We used the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide assay to assess cell viability, flow
      cytometry to analyze cell cycle and apoptosis, and immunoblotting to detect
      protein expression. Resveratrol decreased cell viability at a concentration of
      100 MUmol/l or higher. At a concentration of 50 MUmol/l, resveratrol induced S
      phase arrest of the cell cycle without apoptosis. In addition, phospho-AMPK
      increased significantly in a dose-dependent manner. Resveratrol was found to
      synergistically augment TRAIL-induced apoptosis. The rates of early apoptosis
      were 3.4, 9.6, and 49.6% on treatment with 50 MUmol/l resveratrol, 10 ng/ml
      TRAIL, and both reagents, respectively. Resveratrol significantly downregulated
      the expression of survivin in a dose-dependent manner. In conclusion, we found
      that that resveratrol could augment TRAIL sensitivity by downregulating survivin.
      These results suggest that combination resveratrol with TRAIL may be an effective
      new strategy for the treatment of hepatocellular carcinoma. 

PMID- 24892722
TI  - Antitumor effect of traditional Chinese herbal medicines against lung cancer.
AB  - Traditional Chinese herbal medicine (TCHM) is used widely alone or in combination
      with chemotherapy to treat lung cancer in China. Meta-analysis of clinical trials
      of TCHM against lung cancer suggested the potential, but not confirmed
      therapeutic effect. To gain detailed insight into the antilung cancer effects of
      TCHM, we searched for preclinical studies of TCHM against lung cancer published
      from 1995 to 2012 and systematically analyzed published articles focusing on the
      antitumor effect of individual TCHM in lung cancer cell lines or animal models.
      Among 93 herbal components isolated from 73 Chinese herbs, we found 10 herbal
      compounds that showed the strongest cytotoxicity in lung cancer cell lines
      through apoptosis or cell cycle arrest, and agents isolated from seven Chinese
      herbs that inhibited the primary tumor growth more than 35% in A549 xenografted
      mice models. In addition, three herbal components suppressed lung cancer cell
      migration in vitro at the concentration without cytotoxicity. Polyphyllin I,
      tanshinone IIA, isochaihulactone, 25-OCH3-PPD, and andrographolide were the five
      TCHM compounds that showed strong antilung cancer effects both in cells and in
      animal models, and studies of their analogs showed their structure-activity
      relationships. This review summarizes and analyzes contemporary studies on the
      antitumor effect of individual TCHM against lung cancer and animal models,
      providing perspectives to better understand the TCHM effect in lung cancer
      treatment and develop new antilung cancer drugs from TCHM. 

PMID- 24892720
TI  - Pseudoachondroplasia/COMP - translating from the bench to the bedside.
AB  - Pseudoachondroplasia (PSACH) is a skeletal dysplasia characterized by
      disproportionate short stature, small hands and feet, abnormal joints and early
      onset osteoarthritis. PSACH is caused by mutations in thrombospondin-5 (TSP-5,
      also known as cartilage oligomeric matrix protein or COMP), a pentameric
      extracellular matrix protein primarily expressed in chondrocytes and
      musculoskeletal tissues. The thrombospondin gene family is composed of
      matricellular proteins that associate with the extracellular matrix (ECM) and
      regulate processes in the matrix. Mutations in COMP interfere with calcium
      binding, protein conformation and export to the extracellular matrix, resulting
      in inappropriate intracellular COMP retention. This accumulation of misfolded
      protein is cytotoxic and triggers premature death of chondrocytes during linear
      bone growth, leading to shortened long bones. Both in vitro and in vivo models
      have been employed to study the molecular processes underlying development of the
      PSACH pathology. Here, we compare the strengths and weaknesses of current mouse
      models of PSACH and discuss how the resulting phenotypes may be translated to
      clinical therapies. 

PMID- 24892723
TI  - An overview of randomized clinical trials in metastatic breast cancer: variables
      affecting regulatory drug approval.
AB  - The aim of this study was to analyse trial variables affecting drug approval in
      metastatic breast cancer (MBC). A literature search from 2000 to 2012 retrieved
      66 phase III randomized controlled trials with reported primary endpoints in MBC
      and known outcomes in terms of approval. The influence of the primary endpoint,
      the line of therapy, crossover and the sample size was analysed. The primary
      endpoints used most frequently were progression-free survival (PFS) and time to
      progression or time to treatment failure (N=47; 71%). Overall survival (OS) was a
      primary endpoint in nine trials (14%). In 26 trials (39%), statistically
      significant results were found with respect to the primary endpoint, and in 13
      trials (20%), this was found with respect to the secondary endpoint. Gains in OS
      were found in 12 trials (18%), whereas a benefit to PFS was found in 30 trials
      (46%). The average median OS was 23.1 months. Postprogression survival accounted
      for 64% of OS. Trials with crossover did not have OS as the primary endpoint.
      Trials that resulted in drug approval had a more pronounced gain in OS or PFS and
      had more patients than those without regulatory consequences. PFS was the main
      primary endpoint in randomized clinical trials in MBC and was significantly
      associated with drug approval. OS benefit was rarely achieved in trials where
      this was not the primary endpoint. The number of randomized patients, the primary
      endpoint and crossover are factors linked to regulatory requirements for
      approval, which should be considered in future trial designs. 

PMID- 24892724
TI  - DNA ministrings: highly safe and effective gene delivery vectors.
AB  - Conventional plasmid DNA vectors play a significant role in gene therapy, but
      they also have considerable limitations: they can elicit adverse immune responses
      because of bacterial sequences they contain for maintenance and amplification in
      prokaryotes, their bioavailability is compromised because of their large
      molecular size, and they may be genotoxic. We constructed an in vivo platform to
      produce ministring DNA-mini linear covalently closed DNA vectors-that are devoid
      of unwanted bacterial sequences and encode only the gene(s) of interest and
      necessary eukaryotic expression elements. Transfection of rapidly and slowly
      dividing human cells with ministring DNA coding for enhanced green fluorescent
      protein resulted in significantly improved transfection, bioavailability, and
      cytoplasmic kinetics compared with parental plasmid precursors and isogenic
      circular covalently closed DNA counterparts. Ministring DNA that integrated into
      the genome of human cells caused chromosomal disruption and apoptotic death of
      possibly oncogenic vector integrants; thus, they may be safer than plasmid and
      circular DNA vectors. 

PMID- 24892725
TI  - Aptamer-facilitated Protection of Oncolytic Virus from Neutralizing Antibodies.
AB  - Oncolytic viruses promise to significantly improve current cancer treatments
      through their tumor-selective replication and multimodal attack against cancer
      cells. However, one of the biggest setbacks for oncolytic virus therapy is the
      intravenous delivery of the virus, as it can be cleared from the bloodstream by
      neutralizing antibodies before it reaches the tumor cells. We have selected DNA
      aptamers against an oncolytic virus, vesicular stomatitis virus, using a
      competitive binding approach, as well as against the antigen binding fragment
      (Fab) of antivesicular stomatitis virus polyclonal antibodies, in order to shield
      the virus from nAbs and enhance its in vivo survival. We used flow cytometry to
      identify these aptamers and evaluated their efficiency to shield vesicular
      stomatitis virus in a cell-based plaque forming assay. These oligonucleotides
      were then modified to obtain multivalent binders, which led to a decrease of
      viral aggregation, an increase in its infectivity and an increase in its
      stability in serum. The aptamers were also incubated in nondiluted serum, showing
      their effectiveness under conditions mimicking those in vivo. With this approach,
      we were able to increase viral infectivity by more than 70% in the presence of
      neutralizing antibodies. Thus, this method has the potential to enhance the
      delivery of vesicular stomatitis virus through the bloodstream without
      compromising the patient's immune system. 

PMID- 24892726
TI  - Electrophysiological measurement of interest during walking in a simulated
      environment.
AB  - A reliable neuroscientific technique for objectively estimating the degree of
      interest in a real environment is currently required in the research fields of
      neuroergonomics and neuroeconomics. Toward the development of such a technique,
      the present study explored electrophysiological measures that reflect an
      observer's interest in a nearly-real visual environment. Participants were asked
      to walk through a simulated shopping mall and the attractiveness of the shopping
      mall was manipulated by opening and closing the shutters of stores. During the
      walking task, participants were exposed to task-irrelevant auditory probes (two
      stimulus oddball sequence). The results showed a smaller P2/early P3a component
      of task-irrelevant auditory event-related potentials and a larger lambda response
      of eye-fixation-related potentials in an interesting environment (i.e., open
      shutter condition) than in a boring environment (i.e., closed-shutter condition);
      these findings can be reasonably explained by supposing that participants
      allocated more attentional resources to visual information in an interesting
      environment than in a boring environment, and thus residual attentional resources
      that could be allocated to task-irrelevant auditory probes were reduced. The
      P2/early P3a component and the lambda response may be useful measures of interest
      in a real visual environment. 

PMID- 24892727
TI  - Functions of the C-terminal domains of apoptosis-related proteins of the Bcl-2
      family.
AB  - Bcl-2 family proteins are involved in cell homeostasis, where they regulate cell
      death. Some of these proteins are pro-apoptotic and others pro-survival.
      Moreover, many of them share a similar domain composition with several of the so
      called BH domains, although some only have a BH3 domain. A C-terminal domain is
      present in all the multi-BH domain proteins and in some of the BH3-only ones.
      This C-terminal domain is hydrophobic or amphipathic, for which reason it was
      thought when they were discovered that they were membrane anchors. Although this
      is indeed one of their functions, it has since been observed that they may also
      serve as regulators of the function of some members of this family, such as Bax.
      They may also serve to recognize the target membrane of some of these proteins,
      which only after an apoptotic signal, are incorporated into a membrane. It has
      been shown that peptides that imitate the sequence of C-terminal domains can form
      pores and may serve as a model to design cytotoxic molecules. 

PMID- 24892728
TI  - The significance of functional renal obstruction in predicting pathologic stage
      of upper tract urothelial carcinoma.
AB  - BACKGROUND AND PURPOSE: Assessing the severity of upper tract urothelial
      carcinoma (UTUC) has been difficult because of inadequate biopsy specimens.
      Additional predictive parameters of disease stage would be useful when deciding a
      treatment plan; it has been suggested that preoperative hydronephrosis can be a
      surrogate. We examined the relationship between preoperative ipsilateral renal
      obstruction identified by imaging with final pathologic stage after
      nephroureterectomy (NU) for UTUC. We then analyzed those patients with
      ipsilateral renal obstruction and examined if tumor location is associated with
      an advanced pathologic stage. METHODS: Patients who underwent NU for UTUC between
      the years 2001 to 2013 were analyzed and relevant staging studies and pathology
      were reviewed. Criteria for ipsilateral renal obstruction were defined by the
      presence of a delayed nephrogram on CT scan, renal cortical atrophy with
      associated hydronephrosis on cross-sectional imaging, and/or >10% split function
      discrepancy on nuclear renal scintigraphy with associated hydronephrosis.
      RESULTS: Eighty-two patients met inclusion criteria; 26/82 (31.7%) had locally
      advanced disease (pT3/T4), while 56/82 (63.4%) had organ-confined (<=pT2)
      disease. Of the patients with pT3/T4 disease, 10/26 (38.5%) demonstrated
      radiographic evidence of functional obstruction of the ipsilateral renal unit;
      similarly, in patients with <=pT2 disease, 21/56 (37.5%) demonstrated ipsilateral
      renal obstruction (P=0.93). Of the patients with ipsilateral renal obstruction,
      in those patients with pT3/T4 disease, 7/10 (70.0%) had ureteral tumor
      involvement while 9/21 (42.9%) patients with <=pT2 disease had tumor in the
      ureter (P=0.25). CONCLUSIONS: This study suggests that renal obstruction by
      radiographic analysis does not always predict advanced stage. In addition, there
      is a trend toward advanced stage when a patient has radiographic evidence of
      ipsilateral renal dysfunction and a ureteral tumor.

PMID- 24892729
TI  - Toupet versus Dor as a procedure to prevent reflux after cardiomyotomy for
      achalasia: results of a randomised clinical trial.
AB  - BACKGROUND: The optimal anti-reflux procedure after Heller cardiomyotomy for
      oesophageal achalasia remains unclear. The most commonly used procedure is the
      anterior partial fundoplication according to Dor, although during recent years
      the posterior counterpart (Toupet) has become popular. METHODS: Patients with
      newly diagnosed achalasia and referred for cardiomyotomy were randomised to
      receive either an anterior or partial posterior fundoplication following a
      classical cardiomyotomy. The effect of surgery was assessed during the first
      postoperative year by Eckardt scores, EORTC QLQ-OES18 scores and HRQL
      questionnaires. Timed barium oesophagogram (TBO) and ambulatory 24-h pH
      monitoring were performed to determine oesophageal emptying and the degree of
      reflux control, respectively. RESULTS: Forty-two patients were randomised into
      Dor (n = 20) and Toupet (n = 22) groups. Eckardt scores improved dramatically
      with both procedures, but the EORTC QLQ-OES18 (functional scales) scores revealed
      significantly better relative improvements in the Toupet group compared to the
      Dor repair (P = 0.044). Corresponding advantages in favour of Toupet were
      observed postoperatively in the percentage of oesophageal emptying at TBO (P =
      0.011 in height and P = 0.018 in area), an effect not observed in the Dor group.
      There were no other significant differences recorded between the study groups
      concerning HRQL evaluations and objective assessment of gastro-oesophageal acid
      reflux. CONCLUSIONS: A partial posterior fundoplication after cardiomyotomy seems
      to achieve more improvement in oesophageal emptying and EORTC QLQ-OES18
      functional scale scores than the anterior fundoplication. Otherwise no
      differences between the two anti-reflux repairs were noted. TRIAL REGISTRATION
      NUMBER: ClinicalTrials.gov Identifier: NCT01933373.

PMID- 24892730
TI  - Seasonal changes and endocrine regulation of pejerrey (Odontesthes bonariensis)
      oogenesis in the wild.
AB  - The goal of this study was to evaluate the essential components controlling the
      brain-pituitary-gonad axis during pejerrey (Odontesthes bonariensis) oogenesis in
      the wild. Ovarian developmental stages from vitellogenesis up to ovulation were
      associated with increasing day length and water temperatures below 21 degrees C
      (winter and beginning of spring). Gonadal regression was observed when water
      temperature exceeded this value or when photoperiod decreased. Most females were
      arrested at primary growth stage during summer (high temperature) or at cortical
      alveoli stage between autumn and beginning of winter (short photoperiod). Plasma
      E2 and transcript levels of fshr, cyp19a1b and cyp19a1a increased during
      vitellogenesis, while fshb remained high at all vitellogenic stages. A
      significant correlation between plasma sex steroids (T and E2) and cyp19a1b as
      well as lhcgr transcript levels was observed during vitellogenesis, suggesting a
      steroid positive feedback. Gnrh-I, Gth subunits and lhcgr transcript levels
      increased significantly during late vitellogenesis and final maturation. Present
      results suggest that pejerrey vitellogenesis is controlled by Fsh/Fshr,
      stimulating gonadal aromatase and estradiol synthesis. Moreover, the increase of
      testosterone and estradiol during final vitellogenesis could induce coordinately
      the functioning of the Gnrh/Lh system (perhaps through brain P450 aromatase
      stimulation and brain estradiol increase) and the gonadal Lhcgr synthesis to
      promote the final maturation of oocytes. All these stimulation mechanisms of
      gonadal development would be possible only under permissive environmental
      conditions. 

PMID- 24892731
TI  - Differential detection of tumor cells using a combination of cell rolling,
      multivalent binding, and multiple antibodies.
AB  - Effective quantification and in situ identification of circulating tumor cells
      (CTCs) in blood are still elusive because of the extreme rarity and heterogeneity
      of the cells. In our previous studies, we developed a novel platform that
      captures tumor cells at significantly improved efficiency in vitro using a unique
      biomimetic combination of two physiological processes: E-selectin-induced cell
      rolling and poly(amidoamine) (PAMAM) dendrimer-mediated strong multivalent
      binding. Herein, we have engineered a novel multifunctional surface, on the basis
      of the biomimetic cell capture, through optimized incorporation of multiple
      antibodies directed to cancer cell-specific surface markers, such as epithelial
      cell adhesion molecule (EpCAM), human epidermal growth factor receptor-2 (HER-2),
      and prostate specific antigen (PSA). The surfaces were tested using a series of
      tumor cells, MDA-PCa-2b, MCF-7, and MDA-MB-361, both in mixture in vitro and
      after being spiked into human blood. Our multifunctional surface demonstrated
      highly efficient capture of tumor cells in human blood, achieving up to 82%
      capture efficiency (~10-fold enhancement than a surface with the antibodies
      alone) and up to 90% purity. Furthermore, the multipatterned antibodies allowed
      differential capturing of the tumor cells. These results support that our
      multifunctional surface has great potential as an effective platform that
      accommodates virtually any antibodies, which will likely lead to clinically
      significant, differential detection of CTCs that are rare and highly
      heterogeneous. 

PMID- 24892732
TI  - Symptoms of depression and their management among low-income African-American and
      White mothers in the rural South.
AB  - OBJECTIVE: This study examines experiences of depressive symptoms among a group
      of 32 low-income, African-American and White mothers of young children who
      resided in rural Eastern North Carolina, USA. DESIGN: Women's experiences of
      depressive symptoms were elicited through a series of longitudinal ethnographic
      interviews, including an explanatory models interview specifically designed to
      elicit their beliefs about the causes, symptomatology and help-seeking behavior
      and management of depressive symptoms. RESULTS: A content analysis of interview
      data indicated that most women (11 African-Americans and 15 Whites) reported
      having depressive symptoms currently or in the past. Both African-American and
      White women perceived the main causes of these symptoms as being relationship
      problems with a spouse, a partner, or a family member; lack of finances; and
      parenting stresses. There were no differences in the depressive symptoms African
      American and White women reported, but there were differences in how they managed
      these symptoms and where they sought help. Most of the African-American women
      sought no formal treatment (i.e., pharmacotherapy and/or psychotherapy), but
      instead turned to their religious faith to deal with their feelings. White women
      were more likely to seek formal treatment. CONCLUSION: These findings provide
      insights into the ways in which women in one nonurban area in the USA explained
      and experienced depressive symptoms and demonstrate differences in help-seeking
      behaviors that can be linked to beliefs about depression and perceptions of
      societal responses to those who have it, as well as to perceptions of and
      experiences with the health-care system. Results have implications for the
      implementation of education, intervention, and treatment programs in more
      culturally sensitive ways.

PMID- 24892733
TI  - Structural characterization of lignin from grape stalks (Vitis vinifera L.).
AB  - The chemical structure of lignin from grape stalks, an abundant waste of
      winemaking, has been studied. The dioxane lignin was isolated from extractive-
      and protein-free grape stalks (Vitis vinifera L.) by modified acidolytic
      procedure and submitted to a structural analysis by wet chemistry (nitrobenzene
      and permanganate oxidation (PO)) and spectroscopic techniques. The results
      obtained suggest that grape stalk lignin is an HGS type with molar proportions of
      p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) units of 3:71:26. Structural
      analysis by (1)H and (13)C NMR spectroscopy and PO indicates the predominance of
      beta-O-4' structures (39% mol) in grape stalk lignin together with moderate
      amounts of beta-5', beta-beta, beta-1', 5-5', and 4-O-5' structures. NMR studies
      also revealed that grape lignin should be structurally associated with tannins.
      The condensation degree of grape stalks lignin is higher than that of
      conventional wood lignins and lignins from other agricultural residues. 

PMID- 24892734
TI  - Thoracic surgeons' perception of frail behavior in videos of standardized
      patients.
AB  - BACKGROUND: Frailty is a predictor of poor outcomes following many types of
      operations. We measured thoracic surgeons' accuracy in assessing patient frailty
      using videos of standardized patients demonstrating signs of physical frailty. We
      compared their performance to that of geriatrics specialists. METHODS: We
      developed an anchored scale for rating degree of frailty. Reference categories
      were assigned to 31 videos of standardized patients trained to exhibit five
      levels of activity ranging from "vigorous" to "frail." Following an explanation
      of frailty, thoracic surgeons and geriatrics specialists rated the videos. We
      evaluated inter-rater agreement and tested differences between ratings and
      reference categories. The influences of clinical specialty, clinical experience,
      and self-rated expertise were examined. RESULTS: Inter-rater rank correlation
      among all participants was high (Kendall's W 0.85) whereas exact agreement
      (Fleiss' kappa) was only moderate (0.47). Better inter-rater agreement was
      demonstrated for videos exhibiting extremes of behavior. Exact agreement was
      better for thoracic surgeons (n = 32) than geriatrics specialists (n = 9; p =
      0.045), whereas rank correlation was similar for both groups. More clinical years
      of experience and self-reported expertise were not associated with better inter
      rater agreement. CONCLUSIONS: Videos of standardized patients exhibiting varying
      degrees of frailty are rated with internal consistency by thoracic surgeons as
      accurately as geriatrics specialists when referenced to an anchored scale.
      Ratings were less consistent for moderate degrees of frailty, suggesting that
      physicians require training to recognize early frailty. Such videos may be useful
      in assessing and teaching frailty recognition.

PMID- 24892735
TI  - Enzyme-polysaccharide interaction: a method for improved stability of horseradish
      peroxidase.
AB  - With the advent of green technology, use of enzymes as biocatalyst has become
      increasingly popular. However, in doing so, enzymes can lose their structure and
      catalytic activity under conditions that might be necessary for other components
      of processes. Compared to other strategies, chemical modification is a simple and
      effective technique for generating stable enzyme. Horseradish peroxidase (HRP; EC
      1.11.1.7) was chemically modified by conjugating with 10 different
      polysaccharides. All polysaccharides were found to increase the thermal and pH
      stability of HRP with starch being most promising. Further, different parameters
      were evaluated for effective conjugation and thus stability of HRP conjugate. The
      degradation kinetics and storage stability of HRP proved the conjugate to be 6.4
      times more stable than free enzyme. The starch conjugated HRP and free HRP were
      further evaluated for its application in decolorization of bromophenol blue dye.
      Both the enzymes were able to efficiently (>90%) decolorize the dye within
      minutes. 

PMID- 24892736
TI  - Test performance of sputum microRNAs for lung cancer: a meta-analysis.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide.
      Early detection and precise diagnosis are critical for the patients with lung
      cancer. Increasing evidence has suggested that microRNAs (miRNAs) play important
      roles in the diagnosis of lung cancer. To evaluate the overall diagnostic
      performance of sputum miRNAs for the detection of lung cancer, a meta-analysis
      was performed. METHODS: A systematic search for published literature evaluating
      the diagnostic accuracy of sputum miRNAs in lung cancer was performed to
      determine pooled sensitivity and specificity. A summary receiver operating
      characteristic curve was constructed to assess the overall test performance.
      Subgroup analysis was utilized to explore potential sources of heterogeneity in
      the included studies. RESULTS: Eight studies with a total of 514 patients and 491
      controls were included in this meta-analysis. Sputum miRNAs had a pooled
      sensitivity of 0.70 (95% confidence interval [95% CI]: 0.66-0.70) and a pooled
      specificity of 0.89 (95% CI: 0.86-0.91) for the detection of lung cancer, with an
      area under the summary receiver operating characteristics curve of 0.83.
      Significant interstudy heterogeneity for specificity was observed, with miRNA
      profiles being a possible source. CONCLUSION: Sputum miRNAs are potentially
      useful noninvasive markers for diagnosis of lung cancer. The diagnostic
      specificity of sputum miRNAs may be influenced by the miRNA profiles. It would be
      important for further work to evaluate the generalizability of our results by
      methodologically rigorous studies on a well-defined patient population.

PMID- 24892737
TI  - Phylogeny predicts future habitat shifts due to climate change.
AB  - BACKGROUND: Taxa may respond differently to climatic changes, depending on
      phylogenetic or ecological effects, but studies that discern among these
      alternatives are scarce. Here, we use two species pairs from globally distributed
      spider clades, each pair representing two lifestyles (generalist, specialist) to
      test the relative importance of phylogeny versus ecology in predicted responses
      to climate change. METHODOLOGY: We used a recent phylogenetic hypothesis for
      nephilid spiders to select four species from two genera (Nephilingis and
      Nephilengys) that match the above criteria, are fully allopatric but combined
      occupy all subtropical-tropical regions. Based on their records, we modeled each
      species niche spaces and predicted their ecological shifts 20, 40, 60, and 80
      years into the future using customized GIS tools and projected climatic changes.
      CONCLUSIONS: Phylogeny better predicts the species current ecological preferences
      than do lifestyles. By 2080 all species face dramatic reductions in suitable
      habitat (54.8-77.1%) and adapt by moving towards higher altitudes and latitudes,
      although at different tempos. Phylogeny and life style explain simulated habitat
      shifts in altitude, but phylogeny is the sole best predictor of latitudinal
      shifts. Models incorporating phylogenetic relatedness are an important additional
      tool to predict accurately biotic responses to global change.

PMID- 24892738
TI  - Palliative care clients' and caregivers' notion of fear and their strategies for
      overcoming it.
AB  - OBJECTIVE: This paper aims to clarify our understanding of fear and explore the
      strategies employed by people with life-limiting conditions and their caregivers
      in addressing the emotion of fear as they journey through the dying process. The
      role of fear is discussed: different kinds of fear, the tangible and intangible
      measures by which people manage their fear, and the ways of transcending fear.
      METHOD: The findings of a larger research project funded by the Australian
      Department of Health and Ageing are drawn upon. In-depth interviews were
      conducted with clients and caregivers relating to the psychosocial and emotional
      issues in palliative care. Secondary analysis was utilized to examine the
      perceptions of fear in this cohort. RESULTS: While there were many other
      findings, the results highlighted in this paper relate to the notion of fear
      among interview participants. Interview data showed that people with life
      limiting conditions and their caregivers had different types of fear and employed
      a variety of strategies to deal with fear. Four themes emerged embodying these
      strategies: calling on their own resilience and inner resources, maintaining
      human relationships, gaining the ability to "keep one step ahead" in the dying
      process, and engaging in spirituality and religion. SIGNIFICANCE OF RESULTS: The
      implications of the findings for healthcare professionals are highlighted. The
      recognition of emotions is embedded in palliative care; healthcare professionals
      should view the management of emotions as an integral part of professional
      practice. Addressing fear is essential because unresolved fear can impinge on
      one's ability to cope. Our paper brings together different perspectives on fear
      and how vulnerable individuals attempt to cope with it while at the same time
      providing a view of the challenges confronting healthcare professionals who are
      engaged with them and committed to optimizing health outcomes for palliative care
      clients and their caregivers.

PMID- 24892740
TI  - Kazunori Kataoka editorial.

PMID- 24892739
TI  - In depth analysis of the Helicobacter pylori cag pathogenicity island
      transcriptional responses.
AB  - The severity of symptoms elicited by the widespread human pathogen Helicobacter
      pylori is strongly influenced by the genetic diversity of the infecting strain.
      Among the most important pathogen factors that carry an increased risk for
      gastric cancer are specific genotypes of the cag pathogenicity island (cag-PAI),
      encoding a type IV secretion system (T4SS) responsible for the translocation of
      the CagA effector oncoprotein. To date, little is known about the regulatory
      events important for the expression of a functional cag-T4SS. Here we demonstrate
      that the cag-PAI cistrons are subjected to a complex network of direct and
      indirect transcriptional regulations. We show that promoters of cag operons
      encoding structural T4SS components display homogeneous transcript levels, while
      promoters of cag operons encoding accessory factors vary considerably in their
      basal transcription levels and responses. Most cag promoters are
      transcriptionally responsive to growth-phase, pH and other stress-factors,
      although in many cases in a pleiotropic fashion. Interestingly, transcription
      from the Pcagzeta promoter controlling the expression of transglycolase and T4SS
      stabilizing factors, is triggered by co-culture with a gastric cell line,
      providing an explanation for the increased formation of the secretion system
      observed upon bacterial contact with host cells. Finally, we demonstrate that the
      highly transcribed cagA oncogene is repressed by iron limitation through a direct
      apo-Fur regulation mechanism. Together the results shed light on regulatory
      aspects of the cag-PAI, which may be involved in relevant molecular and
      etiological aspects of H. pylori pathogenesis. 

PMID- 24892741
TI  - Cellular uptake and internalization of hyaluronan-based doxorubicin and cisplatin
      conjugates.
AB  - BACKGROUND: Hyaluronan (HA) is a ligand for the CD44 receptor which is crucial to
      cancer cell proliferation and metastasis. High levels of CD44 expression in many
      cancers have encouraged the development of HA-based carriers for anti-cancer
      therapeutics. PURPOSE: The objective of this study was to determine whether HA
      conjugation of anticancer drugs impacts CD44-specific HA-drug uptake and
      disposition by human head and neck cancer cells. METHODS: The internalization and
      cellular disposition of hyaluronan-doxorubicin (HA-DOX), hyaluronan-cisplatin (HA
      Pt), and hyaluronan-cyanine7 (HA-Cy7) conjugates were investigated by inhibiting
      endocytosis pathways, and by inhibiting the CD44-mediated internalization
      pathways that are known to mediate hyaluronan uptake in vitro. RESULTS: Cellular
      internalization of HA was regulated by CD44 receptors. In mouse xenografts, HA
      conjugation significantly enhanced tumor cell uptake compared to unconjugated
      drugs. DISCUSSION: The results suggested that the main mechanism of HA-based
      conjugate uptake may be active transport via CD44 in conjunction with a clathrin
      dependent endocytic pathway. Other HA receptors, hyaluronan-mediated motility
      receptor (RHAMM) and lymphatic vessel endothelial hyaluronan receptor (LYVE-1),
      did not play a significant role in conjugate uptake. CONCLUSIONS: HA conjugation
      significantly increased CD44-mediated drug uptake and extended the residence time
      of drugs in tumor cells.

PMID- 24892742
TI  - Smart microneedle coatings for controlled delivery and biomedical analysis.
AB  - The work presented demonstrates an unconventional approach in the preparation of
      smart microneedle (MN) coatings utilising electrohydrodynamic atomisation (EHDA)
      principles. Stainless steel (600-900 um in height) MNs were coupled to a ground
      electrode (in the EHDA coating set-up) with the deposition distance and
      collecting methodology varied for an ethanol:methanol (50:50) vehicle system. The
      preparation of nano- and micrometre-scaled pharmaceutical coatings was achieved.
      Fluorescein dye (serving as potential drug, sensory materials or disease state
      markers) and polyvinylpyrrolidone (PVP, polymer matrix system) formed the
      remaining components of the coating formulation. Based on these excipients and by
      varying the coating process, particles (100 nm to 3 um) and fibres (400 nm to 1
      um) were deposited directly on MNs in controlled and selectable fashion (flow
      rates variable ~ 5-50 uL/min, applied voltage variable 6-19 kV). These
      demonstrated options for multiple targeting and analysis applications. The
      underlying EHDA process permits room temperature fabrication, controlled output
      and scale-up potential for emerging MN devices as drug systems or lab-chip
      testing devices.

PMID- 24892743
TI  - The effect of antisense to NF-kappaB in an albumin microsphere formulation on the
      progression of left-ventricular remodeling associated with chronic volume
      overload in rats.
AB  - BACKGROUND: Increased NF-kappaB levels play a crucial role in the pathophysiology
      of heart failure and are known to cause ventricular remodeling. Antisense therapy
      can be used for blocking the expression of NF-kappaB and subsequently avoiding
      heart failure. However, as with most biotechnology products, molecular
      instability and overall cost are often the major issues and concerns limiting the
      advancement of most antisense drugs to the market. Therefore, a cost-efficient
      biodegradable sustained release particle drug delivery system to transport and
      target NF-kB antisense to its intended site of action would be ideal. PURPOSE: To
      evaluate the in vivo performance of a sustained release spray-dried albumin
      microsphere formulation for effective delivery and treatment of left ventricular
      remodeling with antisense to NF-kappaB. METHODS: Albumin-based microspheres
      encapsulating antisense to NF-kB were prepared by spray drying and studied in a
      rat model to treat congestive heart failure. RESULTS: The NF-kappaB activation
      and TNF-alpha release seen in treated animals were significantly lower than
      control animals. Ventricular remodeling was controlled in animals with antisense
      treated AV fistulas as DeltaV0-25 and DeltaV0 were significantly lower compared
      to animals with untreated AV fistulas. CONCLUSION: This treatment was successful
      in curbing ventricular remodeling by suppressing NF-kappaB activation.

PMID- 24892744
TI  - Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.
AB  - Mephedrone is a drug of abuse marketed as 'bath salts". There are discrepancies
      concerning its long-term effects. We have investigated the neurotoxicity of
      mephedrone in mice following different exposition schedules. Schedule 1: four
      doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily
      doses of 25 mg/kg, for two consecutive days. All schedules induced, in some
      animals, an aggressive behavior and hyperthermia as well as a decrease in weight
      gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic
      neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule
      2) only a transient dopaminergic injury was found. In the weekend consumption
      pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss
      that was accompanied by a decrease in tyrosine hydroxylase and tryptophan
      hydroxylase 2 expression one week after exposition. Also, mephedrone induced a
      depressive-like behavior, as well as a reduction in striatal D2 density,
      suggesting higher susceptibility to addictive drugs. In cultured cortical
      neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using
      repeated doses for 2 days in an elevated ambient temperature we evidenced a loss
      of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers
      that suggest injuries at nerve endings. 

PMID- 24892745
TI  - In vivo immunostaining of hemocyte compartments in Drosophila for live imaging.
AB  - In recent years, Drosophila melanogaster has become an attractive model organism
      in which to study the structure and development of the cellular immune
      components. The emergence of immunological markers greatly accelerated the
      identification of the immune cells (hemocytes), while the creation of genetic
      reporter constructs allowed unique insight into the structural organization of
      hematopoietic tissues. However, investigation of the hemocyte compartments by the
      means of immunological markers requires dissection and fixation, which regularly
      disrupt the delicate structure and hamper the microanatomical characterization.
      Moreover, the investigation of transgenic reporters alone can be misleading as
      their expression often differs from the native expression pattern of their
      respective genes. We describe here a method that combines the reporter constructs
      and the immunological tools in live imaging, thereby allowing use of the array of
      available immunological markers while retaining the structural integrity of the
      hematopoietic compartments. The procedure allows the reversible immobilization of
      Drosophila larvae for high-resolution confocal imaging and the time-lapse video
      analysis of in vivo reporters. When combined with our antibody injection-based in
      situ immunostaining assay, the resulting double labeling of the hemocyte
      compartments can provide new information on the microanatomy and functional
      properties of the hematopoietic tissues in an intact state. Although this method
      was developed to study the immune system of Drosophila melanogaster, we
      anticipate that such a combination of genetic and immunological markers could
      become a versatile technique for in vivo studies in other biological systems too.

PMID- 24892747
TI  - Modeling tissue- and mutation- specific electrophysiological effects in the long
      QT syndrome: role of the Purkinje fiber.
AB  - Congenital long QT syndrome is a heritable family of arrhythmias caused by
      mutations in 13 genes encoding ion channel complex proteins. Mounting evidence
      has implicated the Purkinje fiber network in the genesis of ventricular
      arrhythmias. In this study, we explore the hypothesis that long QT mutations can
      demonstrate different phenotypes depending on the tissue type of expression.
      Using computational models of the human ventricular myocyte and the Purkinje
      fiber cell, the biophysical alteration in channel function in LQT1, LQT2, LQT3,
      and LQT7 are modeled. We identified that the plateau potential was important in
      LQT1 and LQT2, in which mutation led to minimal action potential prolongation in
      Purkinje fiber cells. The phenotype of LQT3 mutation was dependent on the
      biophysical alteration induced as well as tissue type. The canonical DeltaKPQ
      mutation causes severe action potential prolongation in both tissue types. For
      LQT3 mutation F1473C, characterized by shifted channel availability, a more
      severe phenotype was seen in Purkinje fiber cells with action potential
      prolongation and early afterdepolarizations. The LQT3 mutation S1904L
      demonstrated striking effects on action potential duration restitution and more
      severe action potential prolongation in Purkinje fiber cells at higher heart
      rates. Voltage clamp simulations highlight the mechanism of effect of these
      mutations in different tissue types, and impact of drug therapy is explored. We
      conclude that arrhythmia formation in long QT syndrome may depend not only on the
      basis of mutation and biophysical alteration, but also upon tissue of expression.
      The Purkinje fiber network may represent an important therapeutic target in the
      management of patients with heritable channelopathies. 

PMID- 24892748
TI  - Non-stomatal limitation to photosynthesis in Cinnamomum camphora seedings exposed
      to elevated O3.
AB  - Ozone (O3) is the most phytotoxic air pollutant for global forests, with
      decreased photosynthesis widely regarded as one of its most common effects.
      However, controversy exists concerning the mechanism that underlies the
      depressing effects of O3 on CO2 assimilation. In the present study, seedlings of
      Cinnamomum camphora, a subtropical evergreen tree species that has rarely been
      studied, were exposed to ambient air (AA), ambient air plus 60 [ppb] O3 (AA+60),
      or ambient air plus 120 [ppb] O3 (AA+120) in open-top chambers (OTCs) for 2
      years. Photosynthetic CO2 exchange and chlorophyll a fluorescence were
      investigated in the second growing season (2010). We aim to determine whether
      stomatal or non-stomatal limitation is responsible for the photosynthesis
      reduction and to explore the potential implications for forest ecosystem
      functions. Results indicate that elevated O3 (E-O3) reduced the net
      photosynthetic rates (PN) by 6.0-32.2%, with significant differences between
      AA+60 and AA+120 and across the four measurement campaigns (MCs). The actual
      photochemical efficiency of photosystem II (PSII) in saturated light (Fv'/Fm')
      was also significantly decreased by E-O3, as was the effective quantum yield of
      PSII photochemistry (PhiPSII). Moreover, E-O3 significantly and negatively
      impacted the maximum rates of carboxylation (Vcmax) and electron transport
      (Jmax). Although neither the stomatal conductance (gs) nor the intercellular CO2
      concentration (Ci) was decreased by E-O3, PN/gs was significantly reduced.
      Therefore, the observed reduction in PN in the present study should not be
      attributed to the unavailability of CO2 due to stomatal limitation, but rather to
      the O3-induced damage to Ribulose-1,5-bisphosphate carboxylase/oxygenase and the
      photochemical apparatus. This suggests that the down-regulation of stomatal
      conductance could fail to occur, and the biochemical processes in protoplasts
      would become more susceptible to injuries under long-term O3 exposure, which may
      have important consequences for forest carbon and water budget. 

PMID- 24892751
TI  - Reductive cross-coupling of nonaromatic, heterocyclic bromides with aryl and
      heteroaryl bromides.
AB  - Reductive cross-coupling allows the direct C-C bond formation between two organic
      halides without the need for preformation of an organometallic reagent. A method
      has been developed for the reductive cross-coupling of nonaromatic, heterocyclic
      bromides with aryl or heteroaryl bromides. The developed conditions use an air
      stable Ni(II) source in the presence of a diamine ligand and a metal reductant to
      allow late-stage incorporation of saturated heterocyclic rings onto aryl halides
      in a functional-group tolerant manner. 

PMID- 24892750
TI  - Ca2+-stabilized adhesin helps an Antarctic bacterium reach out and bind ice.
AB  - The large size of a 1.5-MDa ice-binding adhesin [MpAFP (Marinomonas primoryensis
      antifreeze protein)] from an Antarctic Gram-negative bacterium, M. primoryensis,
      is mainly due to its highly repetitive RII (Region II). MpAFP_RII contains
      roughly 120 tandem copies of an identical 104-residue repeat. We have previously
      determined that a single RII repeat folds as a Ca2+-dependent immunoglobulin-like
      domain. Here, we solved the crystal structure of RII tetra-tandemer (four tandem
      RII repeats) to a resolution of 1.8 A. The RII tetra-tandemer reveals an extended
      (~190-A * ~25-A), rod-like structure with four RII-repeats aligned in series with
      each other. The inter-repeat regions of the RII tetra-tandemer are strengthened
      by Ca2+ bound to acidic residues. SAXS (small-angle X-ray scattering) profiles
      indicate the RII tetra-tandemer is significantly rigidified upon Ca2+ binding,
      and that the protein's solution structure is in excellent agreement with its
      crystal structure. We hypothesize that >600 Ca2+ help rigidify the chain of ~120
      104-residue repeats to form a ~0.6 MUm rod-like structure in order to project the
      ice-binding domain of MpAFP away from the bacterial cell surface. The proposed
      extender role of RII can help the strictly aerobic, motile bacterium bind ice in
      the upper reaches of the Antarctic lake where oxygen and nutrients are most
      abundant. Ca2+-induced rigidity of tandem Ig-like repeats in large adhesins might
      be a general mechanism used by bacteria to bind to their substrates and help
      colonize specific niches. 

PMID- 24892749
TI  - Impairments in the initiation of maternal behavior in oxytocin receptor knockout
      mice.
AB  - Oxytocin (Oxt) acting through its single receptor subtype, the Oxtr, is important
      for the coordination of physiology and behavior associated with parturition and
      maternal care. Knockout mouse models have been helpful in exploring the
      contributions of Oxt to maternal behavior, including total body Oxt knockout (Oxt
      -/-) mice, forebrain conditional Oxtr knockout (Oxtr FB/FB) mice, and total body
      Oxtr knockout (Oxtr -/-) mice. Since Oxtr -/- mice are unable to lactate,
      maternal behavior has only been examined in virgin females, or in dams within a
      few hours of parturition, and there have been no studies that have examined their
      anxiety-like and depression-like behavior following parturition. To improve our
      understanding of how the absence of Oxt signaling affects maternal behavior, mood
      and anxiety, we designed a study using Oxtr -/- mice that separated nursing
      behavior from other aspects of maternal care, such as licking and grooming by
      thelectomizing (i.e. removing the nipples) of Oxtr +/+ mice and sham
      thelectomizing Oxtr -/- mice, and pairing both genotypes with a wet nurse. We
      then measured pup abandonment, maternal behavior, and postpartum anxiety-like and
      depression-like behaviors. We hypothesized that genetic disruption of the Oxtr
      would impact maternal care, mood and anxiety. Specifically, we predicted that
      Oxtr -/- dams would have impaired maternal care and increased anxiety-like and
      depression-like behaviors in the postpartum period. We found that Oxtr -/- dams
      had significantly higher levels of pup abandonment compared to controls, which is
      consistent with previous work in Oxtr FB/FB mice. Interestingly, Oxtr -/- dams
      that initiated maternal care did not differ from wildtype controls in measures of
      maternal behavior. We also did not find any evidence of altered anxiety-like or
      depressive-like behavior in the postpartum period of Oxtr -/- dams. Thus, our
      data suggest that Oxt lowers the threshold for the initiation of maternal
      behavior. 

PMID- 24892752
TI  - Should we still consider Dravet syndrome an epileptic encephalopathy?

PMID- 24892753
TI  - PER2 rs2304672, CLOCK rs1801260, and PER3 rs57875989 polymorphisms are not
      associated with juvenile myoclonic epilepsy.
AB  - Sleep disturbance is common in several epilepsy types, such as juvenile myoclonic
      epilepsy (JME). Genetic background could increase susceptibility to seizure and
      sleep abnormalities. From this perspective, a susceptibility gene for sleep
      disturbance or chronotype could contribute to the genetic susceptibility
      threshold for epilepsy and vice versa. Accordingly, we investigated whether
      functional clock gene polymorphisms (PER2 111C>G, CLOCK 3111T>C, and PER3 VNTR)
      might influence the risk for JME. All these polymorphisms have recently been
      reported to be associated with sleep disturbance, diurnal variation, and
      neurological diseases. The polymorphisms were genotyped in 97 patients and 212
      controls using polymerase chain reaction or restriction fragment length
      polymorphism methods. No significant differences were observed in the genotypic
      and allelic frequencies of these polymorphisms between cases and controls even
      when analyses were restricted to patients that presented a diurnal preferential
      seizure occurrence. We also tested for interactions between polymorphisms by
      multifactor dimensionality reduction analysis. None of the combined genotypes
      differed significantly between the groups. These results present no evidence for
      an association of these polymorphisms with JME. Further studies including other
      types of epilepsy and/or other functional polymorphisms are required to
      investigate the possible relationship between clock genes and the genetic
      susceptibility to chronic seizure.

PMID- 24892754
TI  - Emotion recognition and social cognition in temporal lobe epilepsy and the effect
      of epilepsy surgery.
AB  - The abilities to identify facial expression from another person's face and to
      attribute mental states to others refer to preserved function of the temporal
      lobes. In the present study, we set out to evaluate emotion recognition and
      social cognition in presurgical and postsurgical patients with unilateral
      refractory temporal lobe epilepsy (TLE). The aim of our study was to investigate
      the effects of TLE surgery and to identify the main risk factors for impairment
      in these functions. We recruited 30 patients with TLE for longitudinal data
      analysis (14 with right-sided and 16 with left-sided TLE) and 74 patients for
      cross-sectional data analysis (37 with right-sided and 37 with left-sided TLE)
      plus 20 healthy controls. Besides standard neuropsychological assessment, we
      administered an analog of the Ekman and Friesen test and the Faux Pas Test to
      assess emotion recognition and social cognition, respectively. Both emotion
      recognition and social cognition were impaired in the group of patients with TLE,
      irrespective of the focus side, compared with healthy controls. The performance
      in both tests was strongly dependent on the intelligence level. Beyond
      intelligence level, earlier age at epilepsy onset, longer disease duration, and
      history of early childhood brain injury predicted social cognition problems in
      patients with TLE. Epilepsy surgery within the temporal lobe seems to have
      neutral effect on patients' performances in both domains. However, there are a
      few individual patients who appear to be at risk of postoperative decline, even
      when seizure freedom is achieved following epilepsy surgery. 

PMID- 24892756
TI  - The affective value of faces in patients achieving long-term seizure freedom
      after temporal lobectomy.
AB  - We investigated different aspects of facial expression evaluation in a
      homogeneous cohort of 42 seizure-free patients with 5 or more years of follow-up
      after temporal lobectomy (TL), with the aim of further characterizing the
      impairment in emotion and social cognition among patients. A group of healthy
      subjects matched for sex, age, and education served as controls. Four tasks of
      facial expression evaluation were used: (a) facial expression recognition, (b)
      rating of the intensity of facial expression, and (c) rating of valence
      (pleasantness) and (d) rating of arousal induced by facial expressions. Patients
      had a worse performance in the recognition task for all negative emotions, while
      no differences in intensity ratings were found. They also reported lower arousal
      ratings than controls for faces showing fear, anger, disgust, and neutral
      expressions, as well as lower valence ratings for all facial expressions except
      those showing happiness. Longer epilepsy duration before TL was negatively
      associated with ratings of arousal and intensity and positively associated with
      valence ratings for fearful facial expressions. This study showed that patients
      who become seizure-free after TL present long-term deficits in several aspects of
      facial expression evaluation. Longitudinal, prospective studies are needed to
      evaluate if social cognition improves or declines after TL. 

PMID- 24892755
TI  - Proconvulsant effects of tramadol and morphine on pentylenetetrazol-induced
      seizures in adult rats using different routes of administration.
AB  - Tramadol is frequently used as a pain reliever. However, it has been sometimes
      noted to have the potential to cause seizures. Because of its dual mechanism of
      action (both opioid and nonopioid), the adverse effect profile of tramadol can be
      different in comparison with single-mechanism opioid analgesics, such as
      morphine. In the present study, the facilitatory effects of tramadol and morphine
      on pentylenetetrazol-induced seizures using different routes of administration
      were compared in rats. Adult female rats were divided into six groups and
      continuously received saline, morphine, or tramadol on a daily basis for 15 days
      [gavage (PO) or intraperitoneal (IP)]. An increasing dose of morphine and
      tramadol was used to prevent resistance to repetitive dose (20-125 mg/kg).
      Following one week of withdrawal period and 30 min before the seizure induction
      (PTZ=80 mg/kg, IP), each group of rats was further divided into subgroups that
      received saline, morphine, or tramadol for the second time on the 22nd day of the
      experiment. Results showed that, while morphine, tramadol, and their
      administration had different effects on seizure behaviors, both acute and chronic
      administrations of morphine and tramadol potentiated PTZ-induced seizures.
      However, there was no significant difference between morphine and tramadol in
      terms of seizure severity. Effects of morphine and tramadol on PTZ-induced
      seizures were also stable following one week of withdrawal. In conclusion, this
      study indicated similar severity in the proconvulsant effect of morphine and
      tramadol on PTZ-induced seizures, which might depend on their similar effects on
      GABAergic pathways.

PMID- 24892757
TI  - Editorial: molecular obesity research: lessons learned?

PMID- 24892760
TI  - Targeting the motor end plates in the mouse hindlimb gives access to a greater
      number of spinal cord motor neurons: an approach to maximize retrograde
      transport.
AB  - Lower motor neuron dysfunction is one of the most debilitating neurological
      conditions and, as such, significantly impacts on the quality of life of affected
      individuals. Within the last decade, the engineering of mouse models of lower
      motor neuron diseases has facilitated the development of new therapeutic
      scenarios aimed at delaying or reversing the progression of these conditions. In
      this context, motor end plates (MEPs) are highly specialized regions on the
      skeletal musculature that offer minimally invasive access to the pre-synaptic
      nerve terminals, henceforth to the spinal cord motor neurons. Transgenic
      technologies can take advantage of the relationship between the MEP regions on
      the skeletal muscles and the corresponding motor neurons to shuttle therapeutic
      genes into specific compartments within the ventral horn of the spinal cord. The
      first aim of this neuroanatomical investigation was to map the details of the
      organization of the MEP zones for the main muscles of the mouse hindlimb. The
      hindlimb was selected for the present work, as it is currently a common target to
      challenge the efficacy of therapies aimed at alleviating neuromuscular
      dysfunction. This MEP map was then used to guide series of intramuscular
      injections of Fluoro-Gold (FG) along the muscles' MEP zones, therefore revealing
      the distribution of the motor neurons that supply them. Targeting the entire MEP
      regions with FG increased the somatic availability of the retrograde tracer and,
      consequently, gave rise to FG-positive motor neurons that are organized into
      rostro-caudal columns spanning more spinal cord segments than previously
      reported. The results of this investigation will have positive implications for
      future studies involving the somatic delivery and retrograde transport of
      therapeutic transgenes into affected motor neurons. These data will also provide
      a framework for transgenic technologies aiming at maintaining the integrity of
      the neuromuscular junction for the treatment of lower motor neuron dysfunctions. 

PMID- 24892761
TI  - Extracellular proteolysis of reelin by tissue plasminogen activator following
      synaptic potentiation.
AB  - The secreted glycoprotein reelin plays an indispensable role in neuronal
      migration during development and in regulating adult synaptic functions. The
      upstream mechanisms responsible for initiating and regulating the duration and
      magnitude of reelin signaling are largely unknown. Here we report that reelin is
      cleaved between EGF-like repeats 6-7 (R6-7) by tissue plasminogen activator (tPA)
      under cell-free conditions. No changes were detected in the level of reelin and
      its fragments in the brains of tPA knockouts, implying that other unknown
      proteases are responsible for generating reelin fragments found constitutively in
      the adult brain. Induction of NMDAR-independent long-term potentiation with the
      potassium channel blocker tetraethylammonium chloride (TEA-Cl) led to a specific
      up-regulation of reelin processing at R6-7 in wild-type mice. In contrast, no
      changes in reelin expression and processing were observed in tPA knockouts
      following TEA-Cl treatment. These results demonstrate that synaptic potentiation
      results in tPA-dependent reelin processing and suggest that extracellular
      proteolysis of reelin may regulate reelin signaling in the adult brain. 

PMID- 24892762
TI  - Resolvin D1 and lipoxin A4 improve alveolarization and normalize septal wall
      thickness in a neonatal murine model of hyperoxia-induced lung injury.
AB  - BACKGROUND: The critical fatty acids Docosahexaenoic Acid (DHA) and Arachidonic
      Acid (AA) decline in preterm infants within the first postnatal week and are
      associated with neonatal morbidities, including bronchopulmonary dysplasia (BPD).
      DHA and AA are precursors to downstream metabolites that terminate the
      inflammatory response. We hypothesized that treatment with Resolvin D1 and/or
      Lipoxin A4 would prevent lung injury in a murine model of BPD. OBJECTIVE: To
      determine the effect of Resolvin D1 and/or Lipoxin A4 on hyperoxia-induced lung
      injury. METHODS: C57/BL6 pups were randomized at birth to Room Air, Hyperoxia
      (>90% oxygen), Hyperoxia + Resolvin D1, Hyperoxia + Lipoxin A4, or Hyperoxia +
      Resolvin D1/Lipoxin A4. Resolvin D1 and/or Lipoxin A4 (2 ng/g) were given IP on
      days 0, 3, 6, and 9. On day 10, mice were sacrificed and lungs collected for
      morphometric analyses including Mean Linear Intercept (MLI), Radial Alveolar
      Count (RAC), and Septal Thickness (ST); RT-PCR analyses of biomarkers of lung
      development and inflammation; and ELISA for TGFbeta1 and TGFbeta2. RESULT: The
      increased ST observed with hyperoxia exposure was normalized by both Resolvin D1
      and Lipoxin A4; while, hyperoxia-induced alveolar simplification was attenuated
      by Lipoxin A4. Relative to hyperoxia, Resolvin D1 reduced the gene expression of
      CXCL2 (2.9 fold), TIMP1 (6.7 fold), and PPARgamma (4.8 fold). Treatment with
      Lipoxin A4 also led to a reduction of CXCL2 (2.4 fold) while selectively
      increasing TGFbeta2 (2.1 fold) and Smad3 (1.58 fold). CONCLUSION: The histologic
      and biochemical changes seen in hyperoxia-induced lung injury in this murine
      model can be reversed by the addition of DHA and AA fatty acid downstream
      metabolites that terminate the inflammatory pathways and modulate growth factors.
      These fatty acids or their metabolites may be novel therapies to prevent or treat
      lung injury in preterm infants.

PMID- 24892764
TI  - Effect of iodine restriction on thyroid function in subclinical hypothyroid
      patients in an iodine-replete area: a long period observation in a large-scale
      cohort.
AB  - BACKGROUND: Excessive iodine intake is related to a higher prevalence of
      hypothyroidism, including subclinical hypothyroidism (SCH), in iodine-replete
      areas. This study aimed to evaluate the effect of iodine restriction on thyroid
      function in SCH patients in an iodine-replete area and analyze the relationship
      between serum thyrotropin (TSH) levels and iodine intake. METHODS: The study
      consisted of 146 consecutive patients who were diagnosed with SCH at the Samsung
      Medical Center between 2010 and 2012. Urinary iodine concentration (UIC) was
      measured in 82 patients. Of these, 20 patients with UIC < 300 MUg/L were
      excluded, and 62 patients with UIC >= 300 MUg/L were educated about the
      restriction of iodine-rich foods. Following the first follow-up visit, these
      patients were divided into two groups based on the UIC level: group A (well
      controlled iodine intake, UIC < 300 MUg/L, n = 40), and group B (poorly
      controlled iodine intake, UIC >= 300 MUg/L, n = 22). The remaining 64 patients
      did not restrict iodine rich foods (group C). The 82 patients with measured UICs
      were reevaluated every 3-6 months, and the median follow-up was 13 months (range
      3-32 months). Thyroid function and UIC were measured at each visit. The
      correlation between serum TSH level and UIC was determined for the 82 patients in
      whom UIC was measured. RESULTS: Following 3-6 months of iodine restriction, the
      serum TSH levels significantly decreased in group A (from 9.0 mU/L to 4.7 mU/L; p
      < 0.01). In addition, the serum free thyroxine (T4) levels in group A
      significantly increased (from 1.11 +/- 0.23 ng/dL to 1.18 +/- 0.17 ng/dL; p <
      0.05). However, there were no significant changes in serum TSH or free T4 levels
      in groups B and C. Serum TSH levels significantly correlated with UIC (r = 0.33,
      p < 0.01). CONCLUSION: Iodine restriction may normalize or, at the very least,
      decrease serum TSH levels in SCH patients, and serum TSH levels are strongly
      correlated with UIC. Therefore, restriction of iodine intake could be a primary
      treatment option in SCH patients in an iodine-replete area.

PMID- 24892766
TI  - Effects of traumatic brain injury on locomotor adaptation.
AB  - BACKGROUND AND PURPOSE: Locomotor adaptation is a form of short-term learning
      that enables gait modifications and reduces movement errors when the environment
      changes. This adaptation is critical for community ambulation for example, when
      walking on different surfaces. While many individuals with traumatic brain injury
      (TBI) recover basic ambulation, less is known about recovery of more complex
      locomotor skills, like adaptation. The purpose of this study was to investigate
      how TBI affects locomotor adaptation. METHODS: Fourteen adults with TBI and 11
      nondisabled comparison participants walked for 15 minutes on a split-belt
      treadmill with 1 belt moving at 0.7 m/s, and the other at 1.4 m/s. Subsequently,
      aftereffects were assessed and de-adapted during 15 minutes of tied-belt walking
      (both belts at 0.7 m/s). RESULTS: Participants with TBI showed greater asymmetry
      in interlimb coordination on split-belts than the comparison group. Those with
      TBI did not adapt back to baseline symmetry, and some individuals did not store
      significant aftereffects. Greater asymmetry on split-belts and smaller
      aftereffects were associated with greater ataxia. DISCUSSION: Participants with
      TBI were more perturbed by walking on split-belts and showed some impairment in
      adaptation. This suggests a reduced ability to learn a new form of coordination
      to compensate for environmental changes. Multiple interacting factors, including
      cerebellar damage and impairments in higher-level cognitive processes, may
      influence adaptation post-TBI. CONCLUSIONS: Gait adaptation to novel environment
      demands is impaired in persons with chronic TBI and may be an important skill to
      target in rehabilitation. VIDEO ABSTRACT AVAILABLE: (See Video, Supplemental
      Digital Content 1, http://links.lww.com/JNPT/A74) for more insights from the
      authors.

PMID- 24892767
TI  - Under the weather with Ciguatera fish poisoning: climate variables associated
      with increases in suspected cases.

PMID- 24892763
TI  - Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate
      vaccine (PHiD-CV) in young Latin American children: A double-blind randomized
      controlled trial.
AB  - BACKGROUND: The relationship between pneumococcal conjugate vaccine-induced
      antibody responses and protection against community-acquired pneumonia (CAP) and
      acute otitis media (AOM) is unclear. This study assessed the impact of the ten
      valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine
      (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine
      efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP:
      radiologically confirmed CAP with alveolar consolidation/pleural effusion on
      chest X-ray, or non-alveolar infiltrates and C-reactive protein >= 40 ug/ml);
      other protocol-specified outcomes were also assessed. METHODS AND FINDINGS: This
      phase III double-blind randomized controlled study was conducted between 28 June
      2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with
      good access to health care. Approximately 24,000 infants received PHiD-CV or
      hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at
      booster) at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end
      point was planned when 535 first B-CAP episodes, occurring >=2 wk after dose 3,
      were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD
      CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7,
      34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and
      25.7% (95% CI: 8.4%, 39.6%) against World Health Organization-defined
      consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B
      CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per
      protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and
      invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140)
      and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: 
      1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95%
      CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95%
      CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%)
      against any IPD. Results were consistent between intent-to-treat and per-protocol
      analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%)
      and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively.
      There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n =
      11,799; 0.22%) in the control group. A significant study limitation was the lower
      than expected number of captured AOM cases. CONCLUSIONS: Efficacy was
      demonstrated against a broad range of pneumococcal diseases commonly encountered
      in young children in clinical practice. TRIAL REGISTRATION:
      www.ClinicalTrials.gov NCT00466947.

PMID- 24892765
TI  - Lactation stage-related expression of sialylated and fucosylated glycotopes of
      human milk alpha-1-acid glycoprotein.
AB  - BACKGROUND: Because terminal sugars of alpha-1-acid glycoprotein (AGP) are
      reported to be involved in anti-inflammatory and immunomodulatory processes,
      their expressions might have an influence on the proper function of immune system
      of newborns. Here, relative amounts of sialylated and fucosylated glycotopes on
      human milk AGP over normal lactation were investigated. MATERIALS AND METHODS:
      AGP concentration and relative amounts of its sialylated and fucosylated
      glycovariants were analyzed in early colostrum, colostrum, and transitional and
      mature milk samples of 127 healthy mothers by lectin-AGP enzyme-linked
      immunosorbent assay using alpha2,3- and alpha2,6-sialic acid and alpha1,2-,
      alpha1,3-, and alpha1,6-fucose specific biotinylated Maackia amurensis, Sambucus
      nigra, Ulex europaeus, Tetragonolobus purpureus, and Lens culinaris lectins,
      respectively. RESULTS: AGP concentration in human milk was about 30 times lower
      than in plasma of lactating mothers and decreased gradually over lactation. Milk
      AGP showed significantly higher expression of sialylated and fucosylated
      glycotopes in comparison with those of plasma AGP. Milk AGP glycovariants
      containing alpha2,6-sialylated and alpha1,6- and alpha1,2-fucosylated glycotopes
      showed the highest relative amounts in early colostrums. With progression of
      lactation, the expressions of glycotopes alpha1,2-fucosylated decreased starting
      from Day 4 and those of alpha2,6-sialylated and alpha1,6-fucosylated from Day 8
      of lactation, whereas the level of alpha2,3-sialyl-glycotope was almost constant
      over 45 days of lactation. In contrast, the expression of alpha1,3-linked fucose
      on AGP was low in colostrums and significantly higher in transitional and mature
      milk. CONCLUSIONS: The relative amounts of sialylated and fucosylated
      glycovariants of human hindmilk AGP significantly varied between Days 2 and 45 of
      normal lactation.

PMID- 24892768
TI  - The relationship between fragmentation on electrocardiography and in-hospital
      prognosis of patients with acute myocardial infarction.
AB  - BACKGROUND: In patients with acute ST elevation myocardial infarction (STEMI),
      QRS fragmentation was determined as one of the indicators of mortality and
      morbidity. The development of fragmented QRS (fQRS) is related to defects in the
      ventricular conduction system and is linked to myocardial scar and fibrosis.
      MATERIAL AND METHODS: We prospectively enrolled 355 consecutive patients
      hospitalized in the coronary intensive care unit of our hospital with STEMI
      between the years 2010 and 2012 and their electrocardiographic features and the
      frequency of in-hospital cardiac events were evaluated. RESULTS: There were 217
      cases in the fQRS group and 118 cases in the control group. QRS fragmentation was
      found to be a predictor for major cardiac events. In the fragmented QRS group,
      the frequency of in-hospital major cardiac events (MACE) and death were higher
      (MACE p<0.001; death p<0.003). In the fragmented QRS group, the cardiac enzymes
      (Troponin-I, CK-MB) were significantly higher than in the control group
      (p<0.001). In subgroup analyses, apart from the presence of fragmentation, the
      presence of more than 1 type of fragmentation and the number of fragmented
      deviations were also found to be related with MACE. A significant negative
      correlation was observed with the ejection fraction and, in particular, the
      number of fragmented deviations. CONCLUSIONS: Fragmented QRS has emerged as a
      practical and easily identifiable diagnostic tool for predicting in-hospital
      cardiac events in acute coronary syndromes. Patients who present with a
      fragmented QRS demonstrate increased rates of major cardiac events, death risk,
      and low ejection fraction. In patients with STEMI, the presence of fQRS on the
      ECG and number of fQRS derivations are a significant predictor of in-hospital
      major cardiac events.

PMID- 24892769
TI  - Effect of electron (de)localization and pairing in the electrochemistry of
      polyoxometalates: study of Wells-Dawson molybdotungstophosphate derivatives.
AB  - Polyoxometalates (POMs) are inorganic entities featuring extensive and sometimes
      unusual redox properties. In this work, several experimental techniques as well
      as density functional theory (DFT) calculations have been applied to identify and
      assess the relevance of factors influencing the redox potentials of POMs. First,
      the position of the Mo substituent atom in the Wells-Dawson structure, alpha1- or
      alpha2-P2W17Mo, determines the potential of the first 1e(-) reduction wave. For
      P2W(18-x)Mox systems containing more than one Mo atom, reduction takes place at
      successively more positive potentials. We attribute this fact to the higher
      electron delocalization when some Mo oxidizing atoms are connected. After having
      analyzed the experimental and theoretical data for the monosubstituted alpha1-
      and alpha2-P2W17Mo anions, some relevant facts arise that may help to rationalize
      the redox behavior of POMs in general. Three aspects concern the stability of
      systems: (i) the favorable electron delocalization, (ii) the unfavorable e(-)-e(
      ) electrostatic repulsion, and (iii) the favorable electron pairing. They explain
      trends such as the second reduction wave occurring at more positive potentials in
      alpha1- than in alpha2-P2W17Mo, and also the third electron reduction taking
      place at a less negative potential in the case of alpha2, reversing the observed
      behavior for the first and the second waves. In P2W17V derivatives, the nature of
      the first "d" electron is more localized because of the stronger oxidant
      character of V(V). Thus, the reduction potentials as well as the computed
      reduction energies (REs) for the second reduction of either isomer are closer to
      each other than in Mo-substituted POMs. This may be explained by the lack of
      electron delocalization in monoreduced P2W17V(IV) systems.

PMID- 24892771
TI  - Nanotechnology makes biomass electrolysis more energy efficient than water
      electrolysis.
AB  - The energetic convenience of electrolytic water splitting is limited by
      thermodynamics. Consequently, significant levels of hydrogen production can only
      be obtained with an electrical energy consumption exceeding 45 kWh kg(-1)H2.
      Electrochemical reforming allows the overcoming of such thermodynamic limitations
      by replacing oxygen evolution with the oxidation of biomass-derived alcohols.
      Here we show that the use of an original anode material consisting of palladium
      nanoparticles deposited on to a three-dimensional architecture of titania
      nanotubes allows electrical energy savings up to 26.5 kWh kg(-1)H2 as compared
      with proton electrolyte membrane water electrolysis. A net energy analysis shows
      that for bio-ethanol with energy return of the invested energy larger than 5.1
      (for example, cellulose), the electrochemical reforming energy balance is
      advantageous over proton electrolyte membrane water electrolysis.

PMID- 24892772
TI  - In vitro transport and satiety of a beta-lactoglobulin dipeptide and beta
      casomorphin-7 and its metabolites.
AB  - Understanding the digestive behaviour and biological activities of dairy proteins
      may help to develop model dairy products with targeted health outcomes including
      increased satiety and healthy weight maintenance. Caseins and whey proteins
      constitute over 95% of milk proteins with consumption of these proteins
      associated with increased satiety and a decreased prevalence of metabolic
      disorders. To investigate the in vitro digestive behaviour and satiety of dairy
      proteins at the intestinal epithelium, the in vitro transport and hydrolysis of
      500-2000 MUM beta-casomorphin-7 (YPFPGPI or beta-CM7) and a beta-lactoglobulin
      (beta-Lg) dipeptide (YL) was measured using Caco-2 cell monolayers grown on
      transwells as a model of the intestinal epithelium. Transport of YL was
      concentration dependent and ranged from 0.37-5.26 * 10(-6) cm s(-1), whereas
      transport of beta-CM7 was only detected at 2000 MUM and was significantly lower
      at 0.13 * 10(-6) cm s(-1). Rapid hydrolysis of beta-CM7 in the apical chamber by
      the Caco-2 cells produced three peptide metabolites: YP, GPI and FPGPI. All of
      these metabolites were detected in the basolateral chamber after 30 min with both
      the YP and GPI peptides transporting at a higher rate than intact beta-CM7. In
      vitro satiety was indicated by the secretion of cholecystokinin [26-33] (CCK-8)
      and glucagon-like peptide 1 (GLP-17-36NH2) in the STC-1 enteroendocrine cell
      model. CCK-8 secretion was highest in response to beta-CM7 followed by the beta
      CM7 metabolite FPGPI. CCK-8 secretion however was not significantly stimulated by
      the tri- or dipeptides. Secretion of GLP-1 was not significantly stimulated by
      beta-CM7 or YL. These in vitro results suggest that dairy peptide size enhances
      CCK-8 secretion, whilst limiting transport across Caco-2 monolayers. 

PMID- 24892774
TI  - Fabrication of interfacial functionalized porous polymer monolith and its
      adsorption properties of copper ions.
AB  - The interfacial functionalized poly (glycidyl methacrylate) (PGMA) porous
      monolith was fabricated and applied as a novel porous adsorbent for copper ions
      (Cu(2+)). PGMA porous material with highly interconnected pore network was
      prepared by concentrated emulsion polymerization template. Then polyacrylic acid
      (PAA) was grafted onto the interface of the porous monolith by the reaction
      between the epoxy group on PGMA and a carboxyl group on PAA. Finally, the porous
      monolith was interfacial functionalized by rich amount of carboxyl groups and
      could adsorb copper ions effectively. The chemical structure and porous
      morphology of the porous monolith were measured by Fourier transform infrared
      spectroscopy and scanning electron microscopy. Moreover, the effects of pore size
      distribution, pH value, co-existing ions, contacting time, and initial
      concentrations of copper ions on the adsorption capacity of the porous adsorbents
      were studied. 

PMID- 24892775
TI  - Increase of As release and phytotoxicity to rice seedlings in As-contaminated
      paddy soils by Si fertilizer application.
AB  - Silicon (Si) was shown to be able to reduce arsenic (As) uptake by rice in
      hydroponic culture or in low As soils using high Si application rates. However,
      the effect of Si application on As uptake of rice grown in As-contaminated soils
      using Si fertilizer recommendation rate has not been investigated. In this study,
      the effect of Si application using Si fertilizer recommendation rate on As
      release and phytotoxicity in soils with different properties and contents of As
      was examined. The results show that the concentrations of As in soil solutions
      increased after Si applications due to competitive adsorption between As and Si
      on soil solids and the Si concentrations in soil solutions were also elevated to
      beneficial levels for rice growth. The rice seedlings accumulated more As and its
      growth was inhibited by Si application in As contaminated/spiked soils. The
      results indicate that there is an initial aggravation in As toxicity before the
      beneficial effects of Si fertilizing to rice were revealed when Si application
      based on fertilizer recommendation rate to As-contaminated paddy soils.
      Therefore, for As-contaminated paddy soils with high levels of As, the
      application of Si fertilizer could result in increasing As phytotoxicity and
      uptake by rice. 

PMID- 24892777
TI  - Trace elements and nutrients adsorption onto nano-maghemite in a contaminated
      soil solution: A geochemical/statistical approach.
AB  - Two experiments were carried out to study the competition for adsorption between
      trace elements (TEs) and nutrients following the application of nano-maghemite
      (NM) (iron nano-oxide; Fe2O3) to a soil solution (the 0.01molL(-1) CaCl2 extract
      of a TEs-contaminated soil). In the first, the nutrients K, N, and P were added
      to create a set of combinations: potential availability of TEs during their
      interaction with NM and nutrients were studied. In the second, response surface
      methodology was used to develop predictive models by central composite design
      (CCD) for competition between TEs and the nutrients K and N for adsorption onto
      NM. The addition of NM to the soil solution reduced specifically the
      concentrations of available As and Cd, but the TE-adsorption capacity of NM
      decreased as the P concentration increased. The CCD provided more concise and
      valuable information, appropriate to estimate the behavior of NM sequestering
      TEs: according to the suggested models, K(+) and NH4(+) were important factors
      for Ca, Fe, Mg, Mn, Na, and Zn adsorption (Radj(2)=95%, except for Zn with
      Radj(2)=87%). The obtained information and models can be used to predict the
      effectiveness of NM for the stabilization of TEs, crucial during the
      phytoremediation of contaminated soils. 

PMID- 24892776
TI  - Rapid and selective detection of acetone using hierarchical ZnO gas sensor for
      hazardous odor markers application.
AB  - Hierarchical nanostructured ZnO dandelion-like spheres were synthesized via
      solvothermal reaction at 200 degrees C for 4h. The products were pure hexagonal
      ZnO with large exposure of (002) polar facet. Side-heating gas sensor based on
      hierarchical ZnO spheres was prepared to evaluate the acetone gas sensing
      properties. The detection limit to acetone for the ZnO sensor is 0.25ppm. The
      response (Ra/Rg) toward 100ppm acetone was 33 operated at 230 degrees C and the
      response time was as short as 3s. The sensor exhibited remarkable acetone
      selectivity with negligible response toward other hazardous gases and water
      vapor. The high proportion of electron depletion region and oxygen vacancies
      contributed to high gas response sensitivity. The hollow and porous structure of
      dandelion-like ZnO spheres facilitated the diffusion of gas molecules, leading to
      a rapid response speed. The largely exposed (002) polar facets could adsorb
      acetone gas molecules easily and efficiently, resulting in a rapid response speed
      and good selectivity of hierarchical ZnO spheres gas sensor at low operating
      temperature. 

PMID- 24892770
TI  - Decline in estimated glomerular filtration rate and subsequent risk of end-stage
      renal disease and mortality.
AB  - IMPORTANCE: The established chronic kidney disease (CKD) progression end point of
      end-stage renal disease (ESRD) or a doubling of serum creatinine concentration
      (corresponding to a change in estimated glomerular filtration rate [GFR] of -57%
      or greater) is a late event. OBJECTIVE: To characterize the association of
      decline in estimated GFR with subsequent progression to ESRD with implications
      for using lesser declines in estimated GFR as potential alternative end points
      for CKD progression. Because most people with CKD die before reaching ESRD,
      mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION:
      Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and
      223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated
      measure of serum creatinine concentration over 1 to 3 years and outcome data.
      DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or
      standardized analysis of outputs for random-effects meta-analysis conducted
      between July 2012 and September 2013, with baseline estimated GFR values
      collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal
      disease (initiation of dialysis or transplantation) or all-cause mortality risk
      related to percentage change in estimated GFR over 2 years, adjusted for
      potential confounders and first estimated GFR. RESULTS: The adjusted hazard
      ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline.
      Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2,
      the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of -57% in
      estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of -30%. However, changes of 
      30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more
      common than changes of -57% (0.79% [95% CI, 0.52%-1.06%]). This association was
      strong and consistent across the length of the baseline period (1 to 3 years),
      baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10
      year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73
      m2) was 99% (95% CI, 95%-100%) for estimated GFR change of -57%, was 83% (95% CI,
      71%-93%) for estimated GFR change of -40%, and was 64% (95% CI, 52%-77%) for
      estimated GFR change of -30% vs 18% (95% CI, 15%-22%) for estimated GFR change of
      0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%
      63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but
      weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than
      a doubling of serum creatinine concentration occurred more commonly and were
      strongly and consistently associated with the risk of ESRD and mortality,
      supporting consideration of lesser declines in estimated GFR (such as a 30%
      reduction over 2 years) as an alternative end point for CKD progression.

PMID- 24892778
TI  - Cell cycle disruption and apoptosis as mechanisms of toxicity of organochlorines
      in Zea mays roots.
AB  - Organochlorine pesticides (OCPs) are widespread environmental pollutants; two of
      them are highly persistent: lindane (gammaHCH) and chlordecone (CLD). Maize
      plants cope with high levels of OCP-environmental pollution, however little is
      known about cellular mechanisms involved in plant response to such OCP-exposures.
      This research was aimed at understanding the physiological pathways involved in
      the plant response to OCPs in function of a gradient of exposure. Here we provide
      the evidences that OCPs might disrupt root cell cycle leading to a rise in the
      level of polyploidy possibly through mechanisms of endoreduplication. In
      addition, low-to-high doses of gammaHCH were able to induce an accumulation of
      H2O2 without modifying NO contents, while CLD modulated neither H2O2 nor NO
      production. [Ca(2+)]cytosolic, the caspase-3-like activity as well as TUNEL
      positive nuclei and IP-positive cells increased after exposure to low-to-high
      doses of OCPs. These data strongly suggest a cascade mechanism of the OCP-induced
      toxic effect, notably with an increase in [Ca(2+)]cytosolic and caspase-3-like
      activity, suggesting the activation of programmed cell death pathway. 

PMID- 24892773
TI  - PharmGKB summary: very important pharmacogene information for N-acetyltransferase
      2.

PMID- 24892780
TI  - Asymmetric dearomatic Diels-Alder reactions of diverse heteroarenes via pi-system
      activation.
AB  - An asymmetric dearomatic Diels-Alder protocol for various heteroarenes, such as
      benzofuran, benzothiophene, or even furan, has been developed via pi-system
      activation. This method involves in situ generation of formal trienamine species
      embedding a heteroaromatic moiety, and an array of chiral fused frameworks with
      high molecular complexity and skeletal diversity were efficiently constructed in
      good to excellent stereoselectivity by the catalysis of a cinchona-based primary
      amine. 

PMID- 24892779
TI  - Preparation and characterization of a novel aspirin derivative with anti
      thrombotic and gastric mucosal protection properties.
AB  - The use of acetylsalicylic acid (ASP) is limited by its adverse effects,
      especially the effect on the gastric mucosa. To address this problem, we
      synthesized a derivative form of ASP, prepared by modification of ASP with nano
      hydroxyapatite (a kind of inorganic particle containing Ca(2+)). The derivative
      was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate
      containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5
      mmol per kg body weight) showed similar anti-thrombotic activity as those given
      the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2
      versus UI: 12.5). These rats also showed reduced expression of COX-2, but their
      COX-1 expression was similar to that of control rats, but significantly higher
      than that of ASP-administered rats. Furthermore, the level of prostaglandin E2
      (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered
      rats. Taken together, the results showed that Ca-ASP possessed similar
      antithrombotic activity as ASP but without the side effect associated with ASP,
      and the underlying mechanism may center on inhibiting COX-2 without inhibiting
      COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a
      vital role in the suppression of platelet aggregation and thrombosis, as well as
      in the repair of gastric damage.

PMID- 24892782
TI  - Highly sensitive and selective photoelectrochemical biosensor platform for
      polybrominated diphenyl ether detection using the quantum dots sensitized three
      dimensional, macroporous ZnO nanosheet photoelectrode.
AB  - A novel photoelectrochemical (PEC) immunosensor for the rapid detection of
      2,3',4,5',6-pentabromodiphenylether (BDE-121) was developed by coating a core
      shell ZnS/CdTe/Mn-CdS/ZnS sensitized macroporous ZnO nanosheet (NS)
      photoelectrode with anti-BDE-121 polyclonal antibody. Here, core-shell CdTe/Mn
      CdS quantum dots (QDs) benefit the signal amplification and photostability of the
      co-sensitized ZnO NS photoelectrode. After introducing the ZnS buffer layers
      between different interfaces (the ZnO NS and sensitizers; sensitizers and the
      electrolyte), the photoresponse was further enhanced. Under standard simulated
      illumination, the saturation photocurrent density of the co-sensitized
      photoelectrode is 6.23 mA cm(-2), the highest value reported to date for ZnO NS
      based photoelectrode. The BDE-121 was detected by monitoring the changes of the
      photocurrent signals of the immunosensor resulting from the immunoreaction. The
      immunosensor is sensitive, stable and highly specific toward BDE-121, displaying
      a linear range of 5 pM to 100 nM with a limit of detection of 3.98 pM. BDE-121 in
      paint samples was analyzed with the proposed sensor and gas chromatography-mass
      spectrometry (GC/MS), giving contents of 1.32 +/- 0.02 ng mL(-1) and 1.16 ng mL(
      1), respectively.

PMID- 24892781
TI  - Evolutionary divergence of geographic subspecies within the scalloped spiny
      lobster Panulirus homarus (Linnaeus 1758).
AB  - Panulirus homarus is an economically important spiny lobster that is widespread
      through the Indo-West Pacific Region, but has an uncertain taxonomic status, with
      three or four geographic subspecies having been described. This study used
      mitochondrial (16S, COI and control region) and nuclear (18S, ITS-1) DNA
      sequences to examine specimens of all putative subspecies and forms from
      throughout their range, in order to determine their genetic validity, and
      understand the evolutionary history of this species. Despite the range of
      diversity present in the loci examined, the results were consistent across genes.
      P. h. rubellus from the SW Indian Ocean comprised the most divergent lineage that
      was reciprocally monophyletic with respect to all other P. homarus (approx. 9%
      divergence in COI), and has likely evolved reproductive barriers. The putative P.
      h. "Brown" subspecies from the Marquesas Is in the central Pacific also comprised
      a somewhat divergent monophyletic lineage (approx. 3% in COI), but may simply be
      an allopatric population. The widespread P. h. homarus was not diverged at all
      from the described P. h. megasculpta from the NW Indian Ocean. The degree of
      evolutionary divergence of populations at the extremes distribution of the
      species is somewhat surprising, given the long pelagic larval stage, but suggests
      that allopatric speciation has been an important driver in the evolution of the
      genus. 

PMID- 24892783
TI  - Rapid formation of cell-particle complexes via dielectrophoretic manipulation for
      the detection of surface antigens.
AB  - A rapid and simple method for the fabrication of the island patterns with
      particles and cells was applied to detect the presence of specific antigens on
      the cell surface. An upper interdigitated microband array (IDA) electrode was
      mounted on a lower substrate with the same design to fabricate a microfluidic
      channel device for dielectrophoretic manipulation. The electrode grid structure
      was fabricated by rotating the upper template IDA by 90 degrees  relative to the
      lower IDA. A suspension of anti-CD33 modified particles and HL-60 cells was
      introduced into the channel. An AC electrical signal (typically 20 V peak-to
      peak, 100 kHz) was then applied to the bands of the upper and lower IDAs,
      resulting in the formation of island patterns at the intersections with low
      electric fields. Immunoreactions between the antibodies immobilized on the
      accumulated particles and the CD33 present on the surface of the cells led to the
      formation of complexes comprising corresponding antigen-antibody pairs. Non
      specific pairs accumulated at the intersection, which did not form complexes,
      were then dispersed after removal of the applied field. The time required for the
      detection of the formation/dispersion of the complexes is as short as 6 min in
      the present procedure. Furthermore, this novel cell binding assay does not
      require pretreatment such as target labeling or washing of the unbound cells.

PMID- 24892784
TI  - Rapid and multiplex microRNA detection on graphically encoded silica suspension
      array.
AB  - MicroRNA (miRNA), an 18-24-nucleotide noncoding RNA molecule, has become an ideal
      class of biomarker candidates for clinical diagnosis of cancers. By now, a number
      of detection methods for miRNAs have been developed on planar arrays and
      suspension arrays. In this work, we describe a hybridization-triggered
      fluorescence strategy for label-free and multiplex miRNA detection on graphically
      encoded silica suspension array. The total RNA is directly applied for analysis
      with an 8-mer Universal Tag which can be selectively captured by the capture
      probe via base-stacking effects. Benefiting from base-stacking effects, this
      novel method exhibits superb discrimination ability toward the 5' and 3' end
      single-nucleotide alteration. Mature miRNAs can be distinguished from their
      corresponding pre-miRNAs easily. Moreover, the estimated detection limit of 5
      amol is comparable to some of the most sensitive methods. All these mentioned
      characteristics offer exciting possibilities for discovery and clinical
      applications.

PMID- 24892785
TI  - Nanofabricated SERS-active substrates for single-molecule to virus detection in
      vitro: a review.
AB  - The surface-enhanced Raman scattering (SERS) method has great potential for the
      detection of Raman-active species, ranging from single molecules to biomolecules.
      In the last five years, various approaches have been developed to fabricate SERS
      active substrates with high sensitivity using noble metal nanostructures via top
      down, bottom-up, combination, or template-assisted routes. Nanostructured
      substrates with high average SERS enhancement factors (EFs) can now be easily
      produced, with the EF depending strongly on the size and shape of the
      nanostructures that give rise to the effect. For SERS substrates to be used as a
      platform for applications such as trace detection and bio-sensing, several
      issues, including sensitivity, intensity-concentration dependency, and
      selectivity, need to be addressed. Although several challenges remain before SERS
      active substrates become consistent analytical tools, many successful examples
      have been demonstrated with promising results. 

PMID- 24892787
TI  - Physician survey for study of suppressive antiviral treatment to reduce chronic
      ocular disease and postherpetic neuralgia after herpes zoster ophthalmicus.
AB  - OBJECTIVES: The purpose of this study was to develop a consensus regarding the
      appropriate regimen to evaluate long-term suppressive antiviral treatment to
      reduce complications from herpes zoster ophthalmicus (HZO) and identify potential
      study sites. METHODS: In January 2013, a survey of 13 questions was distributed
      among cornea fellowship directors, board members of the Cornea Society and Ocular
      Microbiology and Immunology Group, and Kera-net Listserv members. Questions
      identified respondents' preferred antiviral regimens to administer for chronic or
      recurrent HZO, gauged the level of interest in participation in a planned
      randomized clinical trial, and assessed the number of HZO patients treated among
      specialists in the past year. RESULTS: Of the 171 respondents who completed the
      questionnaire, the majority identified as Kera-net Listserv members (107 of 171,
      63%) and cornea fellowship directors (46 of 171, 27%). First choice of treatment
      was valacyclovir 500 mg 2 times per day (61 of 171, 36%), followed by acyclovir
      800 mg 2 times per day (56 of 171, 33%), and then valacyclovir 1,000 mg daily
      (26.9%, 46 of 171). Among the choices, famciclovir consistently placed last among
      all the respondents (7 of 171, 4%). A majority (106 of 171, 62%) of all
      respondents, including 70% (26 of 37) of U. S. respondents of the high-volume
      practices, were interested in participating in a future randomized clinical trial
      evaluating whether treatment with oral antiviral medications for 1 year decreases
      complications of HZO. CONCLUSIONS: This survey highlights the strong interest in
      and support for further study of suppressive antiviral treatment regimens to
      reduce complications of HZO.

PMID- 24892786
TI  - Enzyme-antibody dual labeled gold nanoparticles probe for ultrasensitive
      detection of kappa-casein in bovine milk samples.
AB  - A dual labeled probe was synthesized by coating gold nanoparticles (AuNPs) with
      anti-kappa-CN monoclonal antibody (McAb) and horseradish peroxidase (HRP) enzyme
      on their surface. The McAb was used as detector and HRP was used as label for
      signal amplification catalytically oxidize the substrate. AuNPs were used as
      bridges between the McAb and HRP. Based on the probe, an immunoassay was
      developed for ultrasensitive detection of kappa-CN in bovine milk samples. The
      assay has a linear response range within 4.2-560 ng mL(-1). The limit of
      detection (LOD) was 4.2 ng mL(-1) which was 10 times lower than that of
      traditional McAb-HRP based ELISA. The recoveries of kappa-CN from three brand
      bovine milk samples were from 95.8% to 111.0% that had a good correlation
      (R(2)=0.998) with those obtained by official standard Kjeldahl method. For higher
      sensitivity and as simple as the traditional ELISA, the developed immunoassay
      could provide an alternative approach for ultrasensitive detection of kappa-CN in
      bovine milk sample.

PMID- 24892788
TI  - Refractory absence epilepsy and glut1 deficiency syndrome: a new case report and
      literature review.
AB  - We report a 12-year-old female patient with a mild phenotype of glucose
      transporter type 1 deficiency syndrome (Glut1D). The clinical picture was
      characterized by refractory absence epilepsy, migraine, and learning
      disabilities. Absence seizures appeared at the age of 4 years, and
      electroencephalogram (EEG) showed irregular discharges of diffuse epileptic
      abnormalities. During the follow-up, seizures became drug resistant, cognitive
      evaluation revealed learning difficulties, and the patient complained migraine
      episodes. The evidence of seizure worsening before meals and the drug resistance
      suggested a Glut1D. Molecular analysis of SLC2A1 gene showed the presence of a
      pathogenic de novo mutation of the gene in heterozygosity (p.Ala275Thr, c.823G >
      A). Our case and the review of literature data on patients with Glut1D and
      absences provide a combination of clinical and EEG keys that should prompt the
      genetic analysis. The Glut1D should be suspected when absence seizures are
      associated with at least one among: irregular ictal EEG discharges, mild mental
      retardation, migraine, microcephaly, drug resistance, and worsening during
      fasting. An early diagnosis allows to establish one of the available ketogenic
      regimens which could modify the natural history of this treatable condition. 

PMID- 24892789
TI  - Ketoprofen-induced formation of amino acid photoadducts: possible explanation for
      photocontact allergy to ketoprofen.
AB  - Photocontact allergy is a well-known side effect of topical preparations of the
      nonsteroidal anti-inflammatory drug ketoprofen. Photocontact allergy to
      ketoprofen appears to induce a large number of photocross allergies to both
      structurally similar and structurally unrelated compounds. Contact and
      photocontact allergies are explained by structural modification of skin proteins
      by the allergen. This complex is recognized by the immune system, which initiates
      an immune response. We have studied ketoprofen's interaction with amino acids to
      better understand ketoprofen's photoallergenic ability. Irradiation of ketoprofen
      and amino acid analogues resulted in four different ketoprofen
      photodecarboxylation products (6-9) together with a fifth photoproduct (5).
      Dihydroquinazoline 5 was shown to be a reaction product between the indole moiety
      of 3-methylindole (Trp analogue) and the primary amine benzylamine (Lys
      analogue). In presence of air, dihydroquinazoline 5 quickly degrades into stable
      quinazolinone 12. The corresponding quinazolinone (17) was formed upon
      irradiation of ketoprofen and the amino acids N-acetyl-l-Trp ethyl ester and l
      Lys ethyl ester. The formation of these models of an immunogenic complex starts
      with the ketoprofen-sensitized formation of singlet oxygen, which reacts with the
      indole moiety of Trp. The formed intermediate subsequently reacts with the
      primary amino functionality of Lys, or its analogue, to form a Trp-Lys adduct or
      a mimic thereof. The formation of a specific immunogenic complex that does not
      contain the allergen but that can still induce photocontact allergy would explain
      the large number of photocross allergies with ketoprofen. These allergens do not
      have to be structurally similar as long as they can generate singlet oxygen. To
      the best of our knowledge, there is no other suggested explanation for
      ketoprofen's photoallergenic properties that can account for the observed
      photocross allergies. The formation of a specific immunogenic complex that does
      not contain the allergen is a novel hypothesis in the field of contact and
      photocontact allergy. 

PMID- 24892790
TI  - A luminescent mixed-lanthanide-organic framework sensor for decoding different
      volatile organic molecules.
AB  - A flexible tripodal polyaromatic acid (4,4',4"-(((2,4,6-trimethylbenzene-1,3,5
      triyl)-tris(methylene))-tris(oxy))tribenzoic acid, H3TCM) was used to adapt the
      coordination sites of lanthanide ions for the construction of microporous
      lanthanide-organic frameworks (LOFs) [LnTCM(H2O)2].3DMF.H2O (Ln-TCM; Ln = La, Eu,
      and/or Tb). In these LOFs, the emission band of TCM matches well with the
      excitation energy of lanthanide ions (Eu(3+) and Tb(3+)) which results in high
      efficient resonance energy transfer from TCM to lanthanide ions. Moreover, the
      mixed EuxTb1-x-TCM has tunable pores to adapt different induced-fit-type host
      guest interactions which can modulate both the energy transfer efficiency from
      TCM to Ln(3+) ions and the energy allocation between Eu(3+) and Tb(3+) ions in
      the luminescence spectra. We demonstrate that the Eu(x)Tb(1-x)-TCM sensor has the
      capability of decoding different volatile organic molecules (VOMs) with a clearly
      differentiable and unique emission intensity ratio of (5)D0 -> (7)F2 (Eu(3+), 614
      nm) to (5)D4 -> (7)F5 (Tb(3+), 545 nm) transitions for every different VOM.
      Compared with the traditional absolute emission intensity method, such a self
      referencing emission intensity strategy has generated self-calibrating, highly
      differentiable, and very stable luminescent signals for decoding different VOMs
      from the unique Eu(x)Tb(1-x)-TCM platform, which has great potential for
      practical applications.

PMID- 24892792
TI  - Investigation of fluorinated (Meth)acrylate monomers and macromonomers suitable
      for a hydroxy-containing acrylate monomer in UV nanoimprinting.
AB  - We investigated reactive fluorinated (meth)acrylate monomers and macromonomers
      that caused segregation at the cured resin surface of a viscous hydroxy
      containing monomer, glycerol 1,3-diglycerolate diacrylate (GDD), and decreased
      the demolding energy in ultraviolet (UV) nanoimprinting with spin-coated films
      under a condensable alternative chlorofluorocarbon gas atmosphere. The X-ray
      photoelectron spectroscopy and contact angle measurements used to determine the
      surface free energy suggested that a nonvolatile silicone-based methacrylate
      macromonomer with fluorinated alkyl groups segregated at the GDD-based cured
      resin surface and decreased the surface free energy, while fluorinated acrylate
      monomers hardly decreased the surface free energy because of their evaporation
      during the annealing of the spin-coated films. The average demolding energy of
      GDD-based cured resins with the macromonomer having fluorinated alkyl groups was
      smaller than that with the macromonomer having hydrocarbon alkyl groups. The
      fluorinated alkyl groups were responsible for decreasing the demolding energy
      rather than the polysiloxane main chains. We demonstrated that the GDD-based UV
      curable resin with the fluorinated silicone-based macromonomer was suitable for
      step-and-repeat UV nanoimprinting with a bare silica mold, in addition to silica
      molds treated by chemical vapor surface modification with trifluoro-1,1,2,2
      tetrahydropropyltrimethoxysilane (FAS3) and tridecafluoro-1,1,2,2
      tetrahydrooctyltrimethoxysilane (FAS13). 

PMID- 24892791
TI  - Prevalence and characteristics of neuropathic pain in leprosy patients treated
      years ago.
AB  - The aim of this study was to determine the prevalence of neuropathic pain, now
      recognized as another late complication of leprosy, and its characteristics among
      leprosy patients. A cross-sectional study was carried out of people treated for
      leprosy up to at least 5 years ago in a rural area of Ethiopia. Seventy-four
      patients were interviewed using the Neuropathic Pain Symptom Inventory (NPSI)
      questionnaire. In total, 78.9% of the patients were female with a mean age of
      42.9. The mean time from initial diagnosis to the time of the study was 28.0
      years, and 73.0% of patients were diagnosed over 20 years ago. Fifty-two (70.3%)
      reported having symptoms suggestive of neuropathic pain and the majority
      described the pain as burning (88.5%), electric (80.8%), stabbing (76.9%),
      cutting (76.9%), tingling (65.4%), squeezing (57.7%), and/or pressure (53.8%).
      The pain caused a severe or moderate impact on daily life in 75% and 57.7% of
      cases, respectively, and 92.3% suffered from disrupted sleep. Eighty percent of
      patients with pain (42/52) took some medication for pain relief. Neuropathic pain
      is common in patients treated for leprosy and in more than half of them, it
      causes disruption in their daily life and sleep, limiting their quality of life
      even more.

PMID- 24892793
TI  - Challenges in disseminating the findings of psychosocial research conducted in a
      non-English speaking country.

PMID- 24892794
TI  - Electron localization function study on the chemical bonding in a real space for
      tetrahedrane, cubane, adamantane, and dodecahedrane and their perfluorinated
      derivatives and radical anions.
AB  - The nature of chemical bonding in caged cycloalkanes CnXn, CnFn(-*), (n = 4, 8,
      20; X = H, F), and C10X16, C10F16(-*), (X = H, F) has been investigated using
      topological analysis of the ELF function, electron density, and the Laplacian of
      electron density at density functional theory (DFT) level. The bonding analysis
      performed for the perfluorinated radical anion of dodecahedrane (C20F20(-*)),
      bestowing an additional electron, shows an unexpected local maximum of the ELF
      inside the carbon cage. The presence of such an attractor confirms the sigma
      stellation concept presented by Irikura (J. Phys. Chem. A 2008, 112, 983) and
      essential change of the electron localization inside the cage. The basin belongs
      to the rare asynaptic type, V(asyn), and its mean electron population is 0.26
      (0.36e). The value of the integrated spin density, 0.13e, shows that both spin-up
      and spin-down electrons reside in the vicinity of the cage center. A similar
      attractor has been found for perfluorinated radical anion of adamantane (C10F16(
      *)). However, the saturation of the basis set suggests that such an attractor may
      be an artifact. For both caged perfluorinated tetrahedrane and cubane (CnFn (-*),
      n = 4, 8), no valence attractors are present inside the cage. Unpaired electron
      density is concentrated mainly on the C-C bonding basins. The results obtained in
      this study are complementary to those based on the molecular orbital theory
      presented by Irikura. 

PMID- 24892796
TI  - Long-term stability of rapid maxillary expansion combined with chincup
      protraction followed by fixed appliances.
AB  - OBJECTIVE: To analyze the long-term stability of rapid maxillary expansion (RME)
      and protraction from chincup therapy in girls with Class III malocclusion.
      MATERIALS AND METHODS: Twenty-two girls (mean age  =  9.1 +/- 0.6 years) with
      Class III malocclusion were treated with combined RME and protraction from a
      chincup, followed by fixed appliances. Lateral cephalograms were evaluated before
      treatment, at the end of a two-phase treatment protocol (mean age  =  15.1 +/-
      1.1 years), and 10.9 +/- 0.5 years after the end of treatment (mean age  =  27.5
      +/- 0.5 years). The control group consisted of 22 matched girls with skeletal
      Class I malocclusion. RESULTS: After treatment, the Class III group showed
      significant improvement of the Class III malocclusion, mainly due to changes in
      the mandible (ie, SNB angle decreased 1.8 +/- 1.6 degrees ) and significant
      improvement of the sagittal maxillomandibular relationship (Wits appraisal
      increased 2.6 +/- 2.1 mm; ANB angle increased 1.0 +/- 0.3 mm). These changes
      remained stable for an average of 10 years after the end of therapy. No tendency
      toward relapse was detected, and the mandibular position showed favorable
      outcomes. CONCLUSIONS: RME and protraction from chincup therapy led to successful
      long-term outcomes in 18 of 22 patients (81.8%). This treatment approach can be
      considered an efficient therapy in growing girls with mild skeletal Class III
      malocclusion caused by maxillary retrusion and mandibular protrusion.

PMID- 24892797
TI  - Neurobiology of DHEA and effects on sexuality, mood and cognition.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the most abundant
      steroid hormones in the humans. However, their physiological significance, their
      mechanisms of action and their possible roles as treatment are not fully
      clarified. Biological actions of DHEA(S) in the brain involve neuroprotection,
      neurite growth, neurogenesis and neuronal survival, apoptosis, catecholamine
      synthesis and secretion, as well as anti-oxidant, anti-inflammatory and
      antiglucocorticoid effects. In addition, DHEA affects neurosteroidogenis and
      endorphin synthesis/release. We also demonstrated in a model of ovariectomized
      rats that DHEA therapy increases proceptive behaviors, already after 1 week of
      treatment, affecting central function of sexual drive. In women, the analyses of
      clinical outcomes are far from being conclusive and many issues should still be
      addressed. Although DHEA preparations have been available in the market since the
      1990s, there are very few definitive reports on the biological functions of this
      steroid. We demonstrate that 1 year DHEA administration at the dose of 10mg
      provided a significant improvement in comparison with vitamin D in sexual
      function and in frequency of sexual intercourse in early postmenopausal women.
      Among symptomatic women, the spectrum of symptoms responding to DHEA requires
      further investigation, to define the type of sexual symptoms (e.g. decreased
      sexual function or hypoactive sexual desire disorder) and the degree of
      mood/cognitive symptoms that could be responsive to hormonal treatment. In this
      regard, our findings are promising, although they need further exploration with a
      larger and more representative sample size. This article is part of a Special
      Issue entitled: Essential role of DHEA. 

PMID- 24892798
TI  - Comparative 2D-DIGE analysis of salinity responsive microsomal proteins from
      leaves of salt-sensitive Arabidopsis thaliana and salt-tolerant Thellungiella
      salsuginea.
AB  - Halophytes have evolved unique molecular strategies to overcome high soil
      salinity but we still know very little about the main mechanisms that these
      plants use to complete their lifecycle under salinity stress. One useful approach
      to further our understanding in this area is to directly compare the response to
      salinity of two closely related species which show diverse levels of salt
      tolerance. Here we present a comparative proteomic study using DIGE of leaf
      microsomal proteins to identify salt-responsive membrane associated proteins in
      Arabidopsis thaliana (a glycophyte) and Thellungiella salsuginea (a halophyte).
      While a small number of distinct protein abundance changes were observed upon
      salt stress in both species, the most notable differences were observed between
      species and specifically, in untreated plants with a total of 36 proteins
      displaying significant abundance changes. Gene ontology (GO) term enrichment
      analysis showed that the majority of these proteins were distributed into two
      functional categories; transport (31%) and carbohydrate metabolism (17%). Results
      identify several novel salt responsive proteins in this system and support the
      theory that T. salsuginea shows a high degree of salt-tolerance because molecular
      mechanisms are primed to deal with the stress. This intrinsic ability to
      anticipate salinity stress distinguishes it from the glycophyte A. thaliana.
      BIOLOGICAL SIGNIFICANCE: There is significant interest in understanding the
      molecular mechanisms that plants use to tolerate salinity as soil salinization is
      becoming an increasing concern for agriculture with high soil Na(+) levels
      leading to reduced yields and economic loss. Much of our knowledge on the
      molecular mechanisms employed by plants to combat salinity stress has come from
      work on salt-sensitive plants, but studies on naturally occurring highly salt
      resistant plants, halophytes, and direct comparisons between closely related
      glycophytes and halophytes, could help to further our understanding of salinity
      tolerance mechanisms. In this study, employing two closely related species which
      differ markedly in their salt-tolerance, we carried out a quantitative proteomic
      approach using 2D-DIGE to identify salt-responsive proteins and compare and
      contrast the differences between the two plant species. Our work complements a
      previous study using iTRAQ technology (34) and highlights the benefits of using
      alternative technologies and approaches to gain a broader representation of the
      salt-responsive proteome in these species.

PMID- 24892795
TI  - Improved testing of recent HIV-1 infections with the BioRad avidity assay
      compared to the limiting antigen avidity assay and BED Capture enzyme
      immunoassay: evaluation using reference sample panels from the German
      Seroconverter Cohort.
AB  - BACKGROUND: The variety and limitations of current laboratory methods for
      estimating HIV-incidence has driven attempts to improve and standardize the
      performance of serological 'Tests for Recent HIV-Infections' (TRI). Primary and
      follow-up HIV-1 positive plasma samples from individuals with well-defined dates
      of infection collected as part of the German Seroconverter Cohort provided
      specimens highly suitable for use in comparing the performance of three TRIs: the
      AWARETM BEDTM EIA HIV-1 Incidence test (BED-CEIA), Genetic systems HIV-1/HIV-2
      Plus O EIA antibody avidity-based assay (BioRad Avidity) and SediaTM HIV-1 LAg
      Avidity EIA (LAg Avidity). METHODS: The evaluation panel included 180 specimens:
      44 from antiretroviral (ARV)-naive individuals with recently acquired HIV
      infection (<= 130 days; 25 B and 19 non-B subtypes) and 136 from long-term (>12
      months) infected individuals [101 ARV-naive subtype B, 16 non-B subtypes, 14 ARV
      treated individuals, 5 slow progressors (SLP)]. RESULTS: For long-term infected,
      ARV-naive individuals the false recent rates (FRR) of both the BioRad and LAg
      Avidity assays were 2% (2/101 for subtype B) and 6% (1/16 for subtype 'non-B'),
      while the FRR of the BED-CEIA was 7% (7/101 for subtype B) and 25% (4/16 for
      subtype 'non-B') (all p>0.05). Misclassification of ARV-treated individuals and
      SLP was rare by LAg (1/14, 0/5) and BioRad Avidity assays (2/14, 1/5) but more
      frequent by BED-CEIA (5/14, 3/5). Among recently-infected individuals (subtype
      B), 60% (15/25) were correctly classified by BED-CEIA, 88% (22/25) by BioRad
      Avidity and significantly fewer by LAg (48%, 12/25) compared to BioRad Avidity (p
      = 0.005) with a higher true-recency rate among non-B infections for all assays.
      CONCLUSIONS: This study using well-characterized specimens demonstrated lower
      FRRs for both avidity methods than with the BED-CEIA. For recently infected
      individuals the BioRad Avidity assay was shown to give the most accurate results.

PMID- 24892799
TI  - Dual role of the cuttlefish salivary proteome in defense and predation.
AB  - We characterized the proteome of the posterior salivary glands of the cephalopod
      S. officinalis by combining de novo RNA sequencing and mass spectrometry. In
      silico analysis of the transcriptome revealed the occurrence of three main
      categories of proteins: enzymes, immune factors and toxins. Protein
      identification by SDS-PAGE and MALDI-TOF/TOF confirmed the occurrence of proteins
      essential to venom-like enzymes: peptidase S1 under four isoforms, phospholipase
      A2 and two toxins. The first toxin is a cystein rich secreted protein (CRISP), a
      common toxin found in all venomous animals. The second one is cephalotoxin, which
      is specific to decabrachia cephalopods. Secretions of the posterior salivary
      glands are transported to the cephalopodium; they are involved in prey catching
      but also in gamete storage, fertilization and egg-laying. The paralyzing activity
      and the antimicrobial effect of saliva suggest a dual role in predation and in
      immune defense in cuttlefish. BIOLOGICAL SIGNIFICANCE: The originality of this
      study lies in the use of a transcriptomic approach (de novo RNA sequencing)
      coupled to a proteomic approach to get an overview of posterior salivary glands
      in S. officinalis. In cephalopods, these glands are involved in predation, more
      precisely in paralyzing preys and digesting them. Our in silico analysis equally
      reveals a role in immune defense as observed in mammals' saliva. Our study also
      shows the specificity of cuttlefish venom, with the identification of
      cephalotoxins, proteins that are not found in octopuses. Finally, we show that
      cuttlefish saliva is a complex mixture that has antibacterial and crippling
      properties, but no lethal effect.

PMID- 24892800
TI  - An experimental limit on the charge of antihydrogen.
AB  - The properties of antihydrogen are expected to be identical to those of hydrogen,
      and any differences would constitute a profound challenge to the fundamental
      theories of physics. The most commonly discussed antiatom-based tests of these
      theories are searches for antihydrogen-hydrogen spectral differences (tests of
      CPT (charge-parity-time) invariance) or gravitational differences (tests of the
      weak equivalence principle). Here we, the ALPHA Collaboration, report a different
      and somewhat unusual test of CPT and of quantum anomaly cancellation. A
      retrospective analysis of the influence of electric fields on antihydrogen atoms
      released from the ALPHA trap finds a mean axial deflection of 4.1 +/- 3.4 mm for
      an average axial electric field of 0.51 V mm(-1). Combined with extensive
      numerical modelling, this measurement leads to a bound on the charge Qe of
      antihydrogen of Q=(-1.3 +/- 1.1 +/- 0.4) * 10(-8). Here, e is the unit charge,
      and the errors are from statistics and systematic effects.

PMID- 24892802
TI  - Rapid optical methods for enantiomeric excess analysis: from enantioselective
      indicator displacement assays to exciton-coupled circular dichroism.
AB  - CONSPECTUS: The advent of high-throughput screening (HTS) for chiral catalysts
      has encouraged the development of fast methods for determining enantiomeric
      excess (ee). Traditionally, chromatographic methods such as chiral HPLC have been
      used for ee determination in HTS. These methods, however, are not optimal because
      of high duty cycle. Their long analysis time results in a bottleneck in the HTS
      process. A more ideal method for HTS that requires less analysis time such as
      chiroptical methods are thus of interest. In this Account, we summarize our
      efforts to develop host-guest systems for ee determination. The first part
      includes our enantioselective indicator displacement assays (eIDAs), and the
      second part focuses on our circular dichroism based host-guest systems. Our first
      eIDA utilizes chiral boronic acid receptors, along with prescreened indicators,
      to determine ee for chiral alpha-hydroxyacids and vicinal diols with +/-7%
      average error (AE). To further the practicality for this system, a HTS protocol
      was developed. Our second eIDA uses diamino chiral ligands and Cu(II) as the
      receptor for the ee determination of alpha-amino acids. The system reported +/
      12% AE, and a HTS protocol was developed for this system. Our first CD based host
      guest system uses metal complexes composed of Cu(I) or Pd(II) with enantiopure
      2,2'-diphenylphosphino-1,1'-binaphthyl (BINAP) as host to determine the ee of
      chiral vicinal diamines (+/-4% AE), primary amines (+/-17% AE), and
      cyclohexanones (+/-7% AE). Primary amines and cyclohexanones were derivatized to
      form chiral imines or chiral hydrazones to allow coordination with the metal
      complex. Upon coordination of chiral analytes, the metal-to-ligand (BINAP) charge
      transfer band was modulated, thus allowing the discrimination of chiral analytes.
      As an effort to improve the accuracy for chiral primary amine ee determination, a
      system with a host composed of o-formylphenyl boronic acid (FPBA) and enantiopure
      1,1'-bi-2-naphthol (BINOL) was used to reduce the AE to +/-5.8%. In the presence
      of amines, the FPBA-BINOL host forms an imine-coordinated boronic ester, thus
      affecting the CD signal of the boron complex. Another chiral primary amine ee
      determination system was developed with Fe(II) and 3-hydroxy-2
      pyridinecarbaldehyde. The chiral imines, formed by the pyridinecarbaldehyde and
      chiral amines, would coordinate to the Fe(II) ion yielding exciton-coupled
      circular dichroism (ECCD) active metal complexes. This system was able to
      determine the ee of chiral amines with +/-5% AE. Furthermore, this imine-Fe(II)
      complex system also successfully determined the ee of alpha-chiral aldehydes with
      +/-5% AE. Other ECCD based hosts were subsequently developed; one with
      bisquinolylpyridylamine and Cu(II) for chiral carboxylates and amino acids and
      another multicomponent system with pyridine chromophores for chiral secondary
      alcohol ee determination. Both of the systems were able to determine ee of the
      chiral analytes with +/-3% AE. Overall, our group has developed ee determining
      host-guest systems that target various functionalities. To date, we are able to
      determine the ee of vicinal diols, alpha-hydroxyacids, vicinal diamines,
      cyclohexanones, amines, alpha-chiral aldehydes, carboxylates, amino acids, and
      secondary alcohols with +/-7% or lower average error. Future development will
      involve improving the average error and employing the current systems to analyze
      real-life samples resulting from parallel syntheses.

PMID- 24892801
TI  - Protein kinase C inhibitors for immune disorders.
AB  - Protein kinase C (PKC) proteins are a group of well-conserved, intracellular
      signaling enzymes expressed in all cells and tissues, including immune cells.
      Much of the molecular insight into PKC immunobiology has been gleaned from
      studies using PKC gene (Prkc) knockout mice and the analysis of different disease
      models in these animals. More-recent studies have revealed that PKCs also have
      crucial roles in the pathogenesis of human immune disorders. Therefore,
      strategies to modulate the functions of PKC enzymes could have a major impact on
      the treatment and therapies of autoimmune diseases and other immune disorders. 

PMID- 24892803
TI  - Accuracy of the composite variability index as a measure of the balance between
      nociception and antinociception during anesthesia.
AB  - BACKGROUND: The Composite Variability Index (CVI), derived from the
      electroencephalogram, was developed to assess the antinociception-nociception
      balance, whereas the Bispectral Index (BIS) was developed to assess the hypnotic
      state during anesthesia. We studied the relationships between these indices,
      level of hypnosis (BIS level), and antinociception (predicted remifentanil effect
      site concentrations, CeREMI) before and after stimulation. Also, we measured
      their association with movement in response to a noxious stimulus. METHODS: We
      randomized 120 patients to one of 12 groups targeting different hypnotic levels
      (BIS 70, 50, and 30) and various CeREMI (0, 2, 4, or 6 ng/mL). At pseudo-steady
      state, baseline values were observed, and a series of stimuli were applied.
      Changes in BIS, CVI, heart rate (HR), and mean arterial blood pressure (MAP)
      between baseline and response period were analyzed in relation to level of
      hypnosis, antinociception, and somatic response to the stimuli. RESULTS: CVI and
      BIS more accurately correlate with somatic response to an Observer Assessment of
      Alertness and Sedation-noxious stimulation than HR, MAP, CeREMI, and propofol
      effect-site concentration (Tukey post hoc tests P < 0.01). Change in CVI is more
      adequate to monitor response to stimulation than changes in BIS, HR, or MAP (as
      described by the Mathews Correlation Coefficient with significance level set at P
      < 0.001). In contrast, none of the candidate analgesic state indices was uniquely
      related to a specific opioid concentration and is extensively influenced by the
      hypnotic state as measured by BIS. CONCLUSIONS: CVI appears to correlate with
      somatic responses to noxious stimuli. However, unstimulated CVI depends more on
      hypnotic drug effect than on opioid concentration.

PMID- 24892804
TI  - Mechanisms of lidocaine's action on subtypes of spinal dorsal horn neurons
      subject to the diverse roles of Na(+) and K(+) channels in action potential
      generation.
AB  - BACKGROUND: Superficial dorsal horn neurons of the spinal cord receive sensory
      information from Adelta and C fibers. According to their response to sustained
      depolarization, these cells can be divided into 3 groups: tonic (TFN), adapting
      (AFN), and single spike firing (SSN) neurons. During spinal and systemic
      administration of lidocaine, these neurons are exposed to different
      concentrations of the local anesthetic lidocaine. In this study, we explored its
      effect on the excitability of sensory neurons. METHODS: Whole-cell patch-clamp
      recordings from dorsal horn neurons of Wistar rats were used to study the action
      of lidocaine on firing properties. To estimate the impact of a blockade of
      voltage-gated potassium channels by lidocaine (100 MUM) on the firing properties
      of different neurons, the sodium and potassium channel inhibition of lidocaine
      was investigated in the light of the effects of tetrodotoxin (TTX, 10 nM) and
      tetraethylammonium (10 mM). For statistical analysis, the Wilcoxon matched-pairs
      signed rank test was used throughout. RESULTS: All 3 types of neurons responded
      to lidocaine with changes in the shape of their action potentials. The peak
      amplitude of the single action potentials was decreased (P = 0.031, P = 0.013,
      and P = 0.014 for SSN, AFN, and TFN neurons, respectively), and the duration of
      the action potentials was increased (P = 0.016, P = 0.032, and P = 0.031 for SSN,
      AFN, and TFN neurons, respectively). The maximum positive slope (P = 0.016 and P
      = 0.0010 for SSN and AFN, respectively) and the negative slope (P = 0.016, P =
      0.0025, and P = 0.020 for SSN, AFN, and TFN neurons, respectively) decreased
      after application of lidocaine. In tonically firing neurons, lidocaine reduced
      the repetitive firing (P = 0.0016), and this effect was mimicked by a combination
      of TTX and tetraethylammonium. In AFN, TTX mimicked the action of lidocaine.
      CONCLUSIONS: Lidocaine at low concentrations suppresses tonic firing neurons by
      interacting with voltage-gated potassium channels. The effects on adapting firing
      neurons can be explained by an interaction with voltage-gated sodium channels. In
      contrast, the firing pattern of SSN is not affected at the administered
      concentrations. This different sensitivity to low concentrations of sodium and
      particularly of potassium channel blockers might represent a novel approach for a
      differentiated blockade of different spinal dorsal horn neurons.

PMID- 24892805
TI  - NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF
      kappaB.
AB  - NOTCH-dependent signaling pathways are critical for normal bone remodeling;
      however, it is unclear if dysfunctional NOTCH activation contributes to
      inflammation-mediated bone loss, as observed in rheumatoid arthritis (RA)
      patients. We performed RNA sequencing and pathway analyses in mesenchymal stem
      cells (MSCs) isolated from transgenic TNF-expressing mice, a model of RA, to
      identify pathways responsible for decreased osteoblast differentiation. 53
      pathways were dysregulated in MSCs from RA mice, among which expression of genes
      encoding NOTCH pathway members and members of the noncanonical NF-kappaB pathway
      were markedly elevated. Administration of NOTCH inhibitors to RA mice prevented
      bone loss and osteoblast inhibition, and CFU-fibroblasts from RA mice treated
      with NOTCH inhibitors formed more new bone in recipient mice with tibial defects.
      Overexpression of the noncanonical NF-kappaB subunit p52 and RELB in a murine
      pluripotent stem cell line increased NOTCH intracellular domain-dependent (NICD
      dependent) activation of an RBPjkappa reporter and levels of the transcription
      factor HES1. TNF promoted p52/RELB binding to NICD, which enhanced binding at the
      RBPjkappa site within the Hes1 promoter. Furthermore, MSC-enriched cells from RA
      patients exhibited elevated levels of HES1, p52, and RELB. Together, these data
      indicate that persistent NOTCH activation in MSCs contributes to decreased
      osteoblast differentiation associated with RA and suggest that NOTCH inhibitors
      could prevent inflammation-mediated bone loss. 

PMID- 24892806
TI  - Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease.
AB  - Microvillus inclusion disease (MVID) is a severe form of congenital diarrhea that
      arises from inactivating mutations in the gene encoding myosin Vb (MYO5B). We
      have examined the association of mutations in MYO5B and disruption of microvillar
      assembly and polarity in enterocytes. Stable MYO5B knockdown (MYO5B-KD) in CaCo2
      BBE cells elicited loss of microvilli, alterations in junctional claudins, and
      disruption of apical and basolateral trafficking; however, no microvillus
      inclusions were observed in MYO5B-KD cells. Expression of WT MYO5B in MYO5B-KD
      cells restored microvilli; however, expression of MYO5B-P660L, a MVID-associated
      mutation found within Navajo populations, did not rescue the MYO5B-KD phenotype
      but induced formation of microvillus inclusions. Microvilli establishment
      required interaction between RAB8A and MYO5B, while loss of the interaction
      between RAB11A and MYO5B induced microvillus inclusions. Using surface
      biotinylation and dual immunofluorescence staining in MYO5B-KD cells expressing
      mutant forms of MYO5B, we observed that early microvillus inclusions were
      positive for the sorting marker SNX18 and derived from apical membrane
      internalization. In patients with MVID, MYO5B-P660L results in global changes in
      polarity at the villus tips that could account for deficits in apical absorption,
      loss of microvilli, aberrant junctions, and losses in transcellular ion transport
      pathways, likely leading to the MVID clinical phenotype of neonatal secretory
      diarrhea. 

PMID- 24892807
TI  - CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells.
AB  - Intracellular therapeutic targets that define tumor immunosuppression in both
      tumor cells and T cells remain intractable. Here, we have shown that
      administration of a covalently linked siRNA to an aptamer (apt) that selectively
      binds cytotoxic T lymphocyte-associated antigen 4 (CTLA4(apt)) allows gene
      silencing in exhausted CD8+ T cells and Tregs in tumors as well as CTLA4
      expressing malignant T cells. CTLA4 expression was upregulated in CD8+ T cells in
      the tumor milieu; therefore, CTLA4(apt) fused to a STAT3-targeting siRNA
      (CTLA4(apt)-STAT3 siRNA) resulted in internalization into tumor-associated CD8+ T
      cells and silencing of STAT3, which activated tumor antigen-specific T cells in
      murine models. Both local and systemic administration of CTLA4(apt)-STAT3 siRNA
      dramatically reduced tumor-associated Tregs. Furthermore, CTLA4(apt)-STAT3 siRNA
      potently inhibited tumor growth and metastasis in various mouse tumor models.
      Importantly, CTLA4 expression is observed in T cells of patients with blood
      malignancies, and CTLA4(apt)-STAT3 siRNA treatment of immunodeficient mice
      bearing human T cell lymphomas promoted tumor cell apoptosis and tumor growth
      inhibition. These data demonstrate that a CTLA4(apt)-based siRNA delivery
      strategy allows gene silencing in both tumor-associated T cells and tumor cells
      and inhibits tumor growth and metastasis.

PMID- 24892808
TI  - Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased
      osmotic pressure.
AB  - The pathogenesis of mucoinfective lung disease in cystic fibrosis (CF) patients
      likely involves poor mucus clearance. A recent model of mucus clearance predicts
      that mucus flow depends on the relative mucin concentration of the mucus layer
      compared with that of the periciliary layer; however, mucin concentrations have
      been difficult to measure in CF secretions. Here, we have shown that the
      concentration of mucin in CF sputum is low when measured by immunologically based
      techniques, and mass spectrometric analyses of CF mucins revealed mucin cleavage
      at antibody recognition sites. Using physical size exclusion
      chromatography/differential refractometry (SEC/dRI) techniques, we determined
      that mucin concentrations in CF secretions were higher than those in normal
      secretions. Measurements of partial osmotic pressures revealed that the partial
      osmotic pressure of CF sputum and the retained mucus in excised CF lungs were
      substantially greater than the partial osmotic pressure of normal secretions. Our
      data reveal that mucin concentration cannot be accurately measured
      immunologically in proteolytically active CF secretions; mucins are
      hyperconcentrated in CF secretions; and CF secretion osmotic pressures predict
      mucus layer-dependent osmotic compression of the periciliary liquid layer in CF
      lungs. Consequently, mucin hypersecretion likely produces mucus stasis, which
      contributes to key infectious and inflammatory components of CF lung disease. 

PMID- 24892809
TI  - Biliary repair and carcinogenesis are mediated by IL-33-dependent cholangiocyte
      proliferation.
AB  - Injury to the biliary epithelium triggers inflammation and fibrosis, which can
      result in severe liver diseases and may progress to malignancy. Development of a
      type 1 immune response has been linked to biliary injury pathogenesis; however, a
      subset of patients with biliary atresia, the most common childhood
      cholangiopathy, exhibit increased levels of Th2-promoting cytokines. The
      relationship among different inflammatory drivers, epithelial repair, and
      carcinogenesis remains unclear. Here, we determined that the Th2-activating
      cytokine IL-33 is elevated in biliary atresia patient serum and in the livers and
      bile ducts of mice with experimental biliary atresia. Administration of IL-33 to
      WT mice markedly increased cholangiocyte proliferation and promoted sustained
      cell growth, resulting in dramatic and rapid enlargement of extrahepatic bile
      ducts. The IL-33-dependent proliferative response was mediated by an increase in
      the number of type 2 innate lymphoid cells (ILC2s), which released high levels of
      IL-13 that in turn promoted cholangiocyte hyperplasia. Induction of the IL
      33/ILC2/IL-13 circuit in a murine biliary injury model promoted epithelial
      repair; however, induction of this circuit in mice with constitutive activation
      of AKT and YAP in bile ducts induced cholangiocarcinoma with liver metastases.
      These findings reveal that IL-33 mediates epithelial proliferation and suggest
      that activation of IL-33/ILC2/IL-13 may improve biliary repair and disruption of
      the circuit may block progression of carcinogenesis. 

PMID- 24892812
TI  - Anti-citrullinated peptide antibodies and rheumatoid factor isotypes in the
      diagnosis of rheumatoid arthritis: an assessment of combined tests.
AB  - ACPA (anti-citrullinated protein antibody) tests are today systematically added
      to clinical and radiological investigations when diagnosing rheumatoid arthritis
      (RA), and the inclusion of ACPA positivity in the new 2010 RA criteria underlines
      their importance. The aim of this study was to determine the sensitivity and
      specificity of different ACPA assays and IgA, IgG and IgM isotypes of rheumatoid
      factor (RF) in a cohort of patients with early RA in order to assess the value of
      combining the tests. The serum samples were obtained from 46 RA patients, 80
      patients with systemic rheumatic disease, and 20 blood donors. ACPAs were
      measured using five different commercial kits. The receiver operating
      characteristic (ROC) curves of the anti-ACPA tests had area under the curve (AUC)
      values of 0.60-0.83. The diagnostic accuracy of the Bio-Rad multiplex flow
      immunoassay, a new technology for ACPA testing, was very similar to that of the
      other widely used commercial immunoassays. The EliA CCP-Phadia test was the most
      specific, and had the best positive likelihood ratio and positive predictive
      values, whereas the anti-CCP Inova 3.1 test was the most sensitive, and had the
      best negative likelihood ratio and negative predictive values. The best
      combination to use for early RA screening was an ACPA test together with IgM and
      IgA RF. 

PMID- 24892810
TI  - Abnormal B cell memory subsets dominate HIV-specific responses in infected
      individuals.
AB  - Recently, several neutralizing anti-HIV antibodies have been isolated from memory
      B cells of HIV-infected individuals. Despite extensive evidence of B cell
      dysfunction in HIV disease, little is known about the cells from which these rare
      HIV-specific antibodies originate. Accordingly, we used HIV envelope gp140 and
      CD4 or coreceptor (CoR) binding site (bs) mutant probes to evaluate HIV-specific
      responses in peripheral blood B cells of HIV-infected individuals at various
      stages of infection. In contrast to non-HIV responses, HIV-specific responses
      against gp140 were enriched within abnormal B cells, namely activated and
      exhausted memory subsets, which are largely absent in the blood of uninfected
      individuals. Responses against the CoRbs, which is a poorly neutralizing epitope,
      arose early, whereas those against the well-characterized neutralizing epitope
      CD4bs were delayed and infrequent. Enrichment of the HIV-specific response within
      resting memory B cells, the predominant subset in uninfected individuals, did
      occur in certain infected individuals who maintained low levels of plasma viremia
      and immune activation with or without antiretroviral therapy. The distribution of
      HIV-specific responses among memory B cell subsets was corroborated by
      transcriptional analyses. Taken together, our findings provide valuable insight
      into virus-specific B cell responses in HIV infection and demonstrate that memory
      B cell abnormalities may contribute to the ineffectiveness of the antibody
      response in infected individuals. 

PMID- 24892811
TI  - Metabolic engineering of Pichia pastoris for production of hyaluronic acid with
      high molecular weight.
AB  - The high molecular weight (>1 MDa) of hyaluronic acid (HA) is important for its
      biological functions. The reported limiting factors for the production of HA with
      high molecular weight (MW) by microbial fermentation are the insufficient HA
      precursor pool and cell growth inhibition. To overcome these issues, the Xenopus
      laevis xhasA2 and xhasB genes encoding hyaluronan synthase 2 (xhasA2) and UDP
      glucose dehydrogenase (xhasB), were expressed in Pichia pastoris widely used for
      production of heterologous proteins. In this study, expression vectors containing
      various combination cassettes of HA pathway genes including xhasA2 and xhasB from
      X. laevis as well as UDP-glucose pyrophosphorylase (hasC), UDP-N
      acetylglucosamine pyrophosphorylase (hasD) and phosphoglucose isomerase (hasE)
      from P. pastoris were constructed and tested. First, HA pathway genes were
      overexpressed using pAO815 and pGAPZB vectors, resulting in the production of 1.2
      MDa HA polymers. Second, in order to decrease hyaluronan synthase expression a
      strong AOX1 promoter in the xhasA2 gene was replaced by a weak AOX2 promoter
      which increased the mean MW of HA to 2.1 MDa. Finally, the MW of HA polymer was
      further increased to 2.5 MDa by low-temperature cultivation (26  degrees C) which
      reduced cell growth inhibition. The yield of HA production by the P. pastoris
      recombinant strains in 1L of fermentation culture was 0.8-1.7 g/L.

PMID- 24892813
TI  - Validation of ambiguous MLPA results by targeted next-generation sequencing
      discloses a nonsense mutation in the DMD gene.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common inherited
      muscular disease and caused by mutations in the DMD gene on the X-chromosome.
      Multiplex ligation-dependent probe amplification (MLPA) is recognized as a
      convenient and reliable technique to detect exon deletion/duplication mutations
      in the DMD gene. Here, we applied targeted semi-conductor next-generation
      sequencing to clarify the cause of ambiguous MLPA results. METHODS: Targeted semi
      conductor next-generation sequencing was carried out using the Inherited Disease
      Panel (IDP) on the Ion Torrent Personal Genome Machine (PGM). RESULTS: MLPA
      analysis disclosed unclassifiable relative peak ratio of exon 18 in a DMD boy.
      His female cousin was indicated to have exon 18 deletion in one allele. To
      validate these incompatible results, targeted next-generation sequencing was
      conducted. A nucleotide change, C.2227 C>T creating a premature stop codon, was
      in exon 18. Concomitantly, both C and T nucleotides were identified in his
      cousin's genome. Ambiguous values of the relative peak ratio in MLPA were
      considered due to the one nucleotide mismatch between the genomic sequence and
      the probe used in MLPA. CONCLUSION: Analysis using IDP on PGM disclosed a
      nonsense mutation in the DMD gene as a cause of ambiguous results of MLPA.

PMID- 24892814
TI  - Toxicokinetics of seven perfluoroalkyl sulfonic and carboxylic acids in pigs fed
      a contaminated diet.
AB  - The transfer of a mixture of perfluoroalkyl acids (PFAAs) from contaminated feed
      into the edible tissues of 24 fattening pigs was investigated. Four
      perfluoroalkyl sulfonic (PFSAs) and three perfluoroalkyl carboxylic acids (PFCAs)
      were quantifiable in feed, plasma, edible tissues, and urine. As percentages of
      unexcreted PFAA, the substances accumulated in plasma (up to 51%), fat, and
      muscle tissues (collectively, meat 40-49%), liver (under 7%), and kidney (under
      2%) for most substances. An exception was perfluorooctanesulfonic acid (PFOS),
      with lower affinity for plasma (23%) and higher for liver (35%). A toxicokinetic
      model is developed to quantify the absorption, distribution, and excretion of
      PFAAs and to calculate elimination half-lives. Perfluorohexanoic acid (PFHxA), a
      PFCA, had the shortest half-life at 4.1 days. PFSAs are eliminated more slowly
      (e.g., half-life of 634 days for PFOS). PFAAs in pigs exhibit longer elimination
      half-lives than in most organisms reported in the literature, but still shorter
      than in humans. 

PMID- 24892815
TI  - Are early continence recovery and oncologic outcomes influenced by use of
      different devices in prostatic apex dissection during laparoscopic radical
      prostatectomy?
AB  - BACKGROUND AND PURPOSE: Treatment of patients with prostate cancer has evolved
      considerably in the last decade, especially in terms of minimization of the
      negative impacts on erectile function and continence to ensure good quality of
      life for treated patients. New surgical devices, such as dissectors and
      hemostatic scalpels, allow precise definition of the surgical field with finer
      dissection of the anatomic structures, with subsequent reductions in operative
      times and better oncologic and functional outcomes. Although monopolar scissors
      (MS) are still widely used, radiofrequency (RF) and ultrasound (US) scalpels have
      been introduced recently in laparoscopic radical prostatectomy (LRP). Despite the
      widespread use of these scalpels, however, few studies have compared these
      devices in terms of oncologic and functional outcomes after radical
      prostatectomy. The present study aimed to prospectively assess the impact of MS,
      RF, and US scalpels on margin status at apex, and recovery of urinary continence
      and erectile function in patients undergoing extraperitoneal LRP. PATIENTS AND
      METHODS: A total of 150 men were prospectively enrolled between September 2009
      and April 2013 and postoperatively evaluated for continence and clinical factors.
      RESULTS: There were no differences in terms of operative times (P=0.9433), blood
      loss (P=0.9681), apical margin positivity (P=0.3965) or postoperative hospital
      stay (P=0.9257) among the groups. Moreover, no differences in the functional
      outcome scores, as evaluated by the International Consultation on Incontinence
      self-administered Questionnaire, at 1, 3, and 6 months postsurgery were observed.
      CONCLUSION: Our study represents the first evaluation of continence recovery in
      LRP with respect to different devices used for prostatic apex dissection. We
      found that the oncologic, functional, and operative outcomes were similar between
      these different devices during LRP, with no scalpel demonstrating superiority in
      continence recovery.

PMID- 24892816
TI  - Medium from gamma-irradiated Escherichia coli bacteria stimulates a unique immune
      response in Drosophila cells.
AB  - It is well known that gamma-irradiated, non-dividing bacteria can elicit potent
      immune responses in mammals. Compared to traditional heat or chemical
      inactivation of microbes, gamma-irradiation likely preserves metabolic activity
      and antigenic features to a larger extent. We have previously shown that
      antimicrobial peptides are induced in Drosophila by peptidoglycan fragments
      secreted into the medium of exponentially growing bacterial cultures. In this
      study, we gamma-irradiated Escherichiacoli cells at a dose that halted cell
      division. The temporal synthesis and release of peptidoglycan fragments were
      followed as well as the potential of bacterial supernatants to induce immune
      responses in Drosophila S2 cells. We demonstrate that peptidoglycan synthesis
      continues for several days post irradiation and that monomeric peptidoglycan is
      shed into the medium. Whole transcriptome analysis revealed a strong immune
      response against the bacterial medium. The response to medium taken directly post
      irradiation shows a large overlap to that of peptidoglycan. Medium from prolonged
      bacterial incubation does, however, stimulate a selective set of immune genes. A
      shift towards a stress response was instead observed with a striking induction of
      several heat shock proteins. Our findings suggest that gamma-irradiated bacteria
      release elicitors that stimulate a novel response in Drosophila. 

PMID- 24892817
TI  - Histamine regulates the inflammatory response of the tunicate Styela plicata.
AB  - Histamine is stored inside hemocytes of the tunicate Styela plicata (Chordata,
      Tunicata, Ascidiacea), but no evidence on its role in the regulation of the
      immune response of this species has been reported. We examined whether histamine
      participated in the regulation of inflammation and host defense in S. plicata.
      The presence of histamine inside S. plicata hemocytes was confirmed by flow
      cytometry, and histamine release was detected by ELISA, after in vitro hemocyte
      stimulation with different PAMPs. In vitro hemocyte treatment with histamine, or
      specific histamine-receptor agonists, reduced their phagocytic ability. Injection
      of histamine into the tunic recruited hemocytes to the site of injection.
      Systemic injection of histamine, or the histamine-releasing agent compound 48/80,
      decreased the phagocytic ability of hemocytes. Histamine promoted the
      constriction of tunic hemolymph vessels in vivo, having a direct effect on
      vasoconstriction in tunic explants. These results provide for the first time
      clear evidence for the involvement of histamine in the regulation of inflammation
      and host defense in tunicates. 

PMID- 24892818
TI  - Effect of melatonin and analogues on corneal wound healing: involvement of Mt2
      melatonin receptor.
AB  - PURPOSE: We have investigated the effect of melatonin and its analogues on rabbit
      corneal epithelial wound healing. METHODS: New Zealand rabbits were anaesthetised
      and wounds were made by placing Whatman paper discs soaked in n-heptanol on the
      cornea. Melatonin and analogues (all 10 nmol) were instilled. Wound diameter was
      measured every 2 hours by means of fluorescein application with a Topcon SL-8Z
      slit lamp. Melatonin antagonists (all 10 nmol) were applied 2 hours before the
      application of the n-heptanol-soaked disc and then every 6 hours together with
      melatonin. To confirm the presence of MT2 receptors in corneal epithelial cells
      immunohistochemistry, Western blot and RT-PCR assays in native tissue and in
      rabbit corneal epithelial cells were performed. The tear components were
      extracted then processed by HPLC to quantify melatonin in tears. RESULTS:
      Migration assays revealed that melatonin and particularly the treatment with the
      MT2 agonist IIK7, accelerated the rate of healing (p < 0.001). The application of
      the non-selective melatonin receptor antagonist luzindole and the MT2 antagonist
      DH97 (but not prazosin), prevented the effect of melatonin on wound healing (both
      p < 0.001). Immunohistochemistry, Western blot and RT-PCR assays showed the
      presence of MT2 melatonin receptor in corneal epithelial cells. In addition, we
      have identified melatonin in tears and determined its daily variations.
      CONCLUSIONS: These data suggest that MT2 receptors are implicated in the effect
      of melatonin on corneal wound healing regulating migration rate. This suggests
      the potential use of melatonin and its analogues to enhance epithelial wound
      healing in ocular surface disease.

PMID- 24892820
TI  - Psychosocial experiences in the context of life-threatening illness: the cardiac
      rehabilitation patient.
AB  - OBJECTIVE: One of the most prevalent life-threatening illnesses is heart disease.
      The initial trauma of being diagnosed with a life-threatening illness or having a
      cardiac event can begin a psychosocial chain reaction that results in a
      transformation of the lives of these patients. The goal of our study was to
      investigate the lived experiences of psychosocial healing in rehabilitation of
      cardiac patients using a qualitative written interview. METHOD: A purposive
      sample of 14 cardiac event survivors was recruited. Participants were interviewed
      after informed consent and screening. We used a qualitative analysis and model
      revision approach similar to the procedure outlined by Charmaz (2006). RESULTS:
      Participants consistently mentioned that a heightened awareness of mortality was
      a motivating factor that led to participants focusing more on their family and
      relationships, having an enhanced outlook on life, and making healthy lifestyle
      changes. SIGNIFICANCE OF RESULTS: If clinicians are able to employ a measure to
      better understand the nature of a patient's progression from cardiac event to
      successful recovery, interventions such as cardiac rehabilitation can be
      implemented earlier and more effectively during the course of the illness and
      recovery phases of treatment. Theoretically, this early detection of a patient's
      progression could reduce the time spent recovering from a cardiac event, and it
      would allow treatments for these conditions to better alleviate the psychosocial
      concerns faced by patients.

PMID- 24892821
TI  - Defective regulation of the ubiquitin/proteasome system in the hypothalamus of
      obese male mice.
AB  - In both human and experimental obesity, inflammatory damage to the hypothalamus
      plays an important role in the loss of the coordinated control of food intake and
      energy expenditure. Upon prolonged maintenance of increased body mass, the brain
      changes the defended set point of adiposity, and returning to normal weight
      becomes extremely difficult. Here we show that in prolonged but not in short-term
      obesity, the ubiquitin/proteasome system in the hypothalamus fails to maintain an
      adequate rate of protein recycling, leading to the accumulation of ubiquitinated
      proteins. This is accompanied by an increased colocalization of ubiquitin and p62
      in the arcuate nucleus and reduced expression of autophagy markers in the
      hypothalamus. Genetic protection from obesity is accompanied by the normal
      regulation of the ubiquitin/proteasome system in the hypothalamus, whereas the
      inhibition of proteasome or p62 results in the acceleration of body mass gain in
      mice exposed for a short period to a high-fat diet. Thus, the defective
      regulation of the ubiquitin/proteasome system in the hypothalamus may be an
      important mechanism involved in the progression and autoperpetuation of obesity. 

PMID- 24892819
TI  - Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal
      connection.
AB  - The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune
      sequelae, has acquired a new level of understanding. Studies support the
      hypothesis that molecular mimicry between the group A streptococcus and heart or
      brain are important in directing immune responses in rheumatic fever. Rheumatic
      carditis, Sydenham chorea and a new group of behavioral disorders called
      pediatric autoimmune neuropsychiatric disorders associated with streptococcal
      infections are reviewed with consideration of autoantibody and T cell responses
      and the role of molecular mimicry between the heart, brain and group A
      streptococcus as well as how immune responses contribute to pathogenic mechanisms
      in disease. In rheumatic carditis, studies have investigated human monoclonal
      autoantibodies and T cell clones for their crossreactivity and their mechanisms
      leading to valve damage in rheumatic heart disease. Although studies of human and
      animal sera from group A streptococcal diseases or immunization models have been
      crucial in providing clues to molecular mimicry and its role in the pathogenesis
      of rheumatic fever, study of human monoclonal autoantibodies have provided
      important insights into how antibodies against the valve may activate the valve
      endothelium and lead to T cell infiltration. Passive transfer of anti
      streptococcal T cell lines in a rat model of rheumatic carditis illustrates
      effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as
      the neurological manifestation of rheumatic fever for decades, the combination of
      autoimmunity and behavior is a relatively new concept linking brain, behavior and
      neuropsychiatric disorders with streptococcal infections. In Sydenham chorea,
      human mAbs and their expression in transgenic mice have linked autoimmunity to
      central dopamine pathways as well as dopamine receptors and dopaminergic neurons
      in basal ganglia. Taken together, the studies reviewed provide a basis for
      understanding streptococcal sequelae and how immune responses against group A
      streptococci influence autoimmunity and inflammatory responses in the heart and
      brain. 

PMID- 24892822
TI  - The chaperone-like activity of alpha-synuclein attenuates aggregation of its
      alternatively spliced isoform, 112-synuclein in vitro: plausible cross-talk
      between isoforms in protein aggregation.
AB  - Abnormal oligomerization and aggregation of alpha-synuclein (alpha-syn/WT-syn)
      has been shown to be a precipitating factor in the pathophysiology of Parkinson's
      disease (PD). Earlier observations on the induced-alternative splicing of alpha
      syn by Parkinsonism mimetics as well as identification of region specific
      abnormalities in the transcript levels of 112-synuclein (112-syn) in diseased
      subjects underscores the role of 112-syn in the pathophysiology of PD. In the
      present study, we sought to identify the aggregation potential of 112-syn in the
      presence or absence of WT-syn to predict its plausible role in protein
      aggregation events. Results demonstrate that unlike WT-syn, lack of 28 aa in the
      C-terminus results in the loss of chaperone-like activity with a concomitant gain
      in vulnerability to heat-induced aggregation and time-dependent fibrillation. The
      effects were dose and time-dependent and a significant aggregation of 112-syn was
      evident at as low as 45  degrees C following 10 min of incubation. The heat
      induced aggregates were found to be ill-defined structures and weakly positive
      towards Thioflavin-T (ThT) staining as compared to clearly distinguishable ThT
      positive extended fibrils resulting upon 24 h of incubation at 37  degrees C.
      Further, the chaperone-like activity of WT-syn significantly attenuated heat
      induced aggregation of 112-syn in a dose and time-dependent manner. On contrary,
      WT-syn synergistically enhanced fibrillation of 112-syn. Overall, the present
      findings highlight a plausible cross-talk between isoforms of alpha-syn and the
      relative abundance of these isoforms may dictate the nature and fate of protein
      aggregates.

PMID- 24892824
TI  - Assessment of methods used to determine the safety of the topical insect
      repellent N,N-diethyl-m-toluamide (DEET).
AB  - N,N-diethyl-m-toluamide (DEET) has been registered for commercial use as an
      insect repellent for over five decades, and is used widely across the world.
      Concerns over the safety of DEET first emerged during the 1980s after reports of
      encephalopathy following DEET exposure, particularly in children. However, the
      role of DEET in either the illness or deaths was and remains purely speculative.
      In response to these cases a number of reviews and investigations of DEET safety
      were carried out. Here we examine the methods used and information available to
      determine the safety of DEET in humans. Animal testing, observational studies and
      intervention trials have found no evidence of severe adverse events associated
      with recommended DEET use. Minor adverse effects noted in animal trials were
      associated with very large doses and were not replicated between different test
      species. The safety surveillance from extensive humans use reveals no association
      with severe adverse events. This review compares the toxicity assessment using
      three different models to define the risk assessment and safety threshold for
      DEET use in humans and discusses the clinical consequences of the thresholds
      derived from the models.The theoretical risks associated with wearing an insect
      repellent should be weighed against the reduction or prevention of the risk of
      fatal or debilitating diseases including malaria, dengue, yellow fever and
      filariasis. With over 48 million European residents travelling to regions where
      vector borne diseases are a threat in 2009, restricting the concentration of DEET
      containing repellents to 15% or less, as modelled in the 2010 EU directive, is
      likely to result in extensive sub-therapeutic activity where repellents are
      infrequently applied. Future European travellers, as a consequence of inadequate
      personal protection, could potentially be at increased risk of vector borne
      diseases. Risk assessments of repellents should take these factors into account
      when setting safe limits. 

PMID- 24892823
TI  - Interleukin-17A promotes MUC5AC expression and goblet cell hyperplasia in nasal
      polyps via the Act1-mediated pathway.
AB  - BACKGROUND: Recent studies demonstrated that nasal polyps (NP) patients in China
      and other Asian regions possessed distinct Th17-dominant inflammation and
      enhanced tissue remodeling. However, the mechanism underlying these observations
      is not fully understood. This study sought to evaluate the association of
      interleukin (IL)-17A with MUC5AC expression and goblet cell hyperplasia in
      Chinese NP patients and to characterize the signaling pathway underlying IL-17A
      induced MUC5AC expression in vitro. METHOD: We enrolled 25 NP patients and 22
      normal controls and examined the expression of IL-17A, MUC5AC and act1 in polyp
      tissues by immunohistochemical (IHC) staining, quantitative polymerase chain
      reaction (qPCR) and western blot. Moreover, by using an in vitro culture system
      of polyp epithelial cells (PECs), IL-17A-induced gene expression was screened in
      cultured PECs by DNA microarray. The expression of IL-17RA, IL-17RC, act1 and
      MUC5AC and the activation of the MAPK pathway (ERK, p38 and JNK), were further
      examined in cultured PECs and NCI-H292 cells by qPCR and western blotting,
      respectively. RESULTS: We found that increased IL-17A production was
      significantly correlated with MUC5AC and act1 expression and goblet cell
      hyperplasia in polyp tissues (p<0.05). IL-17A significantly stimulated the
      expression of IL-17RA, IL-17RC, act1 and MUC5AC, and the activation of the MAPK
      pathway in cultured PECs and NCI-H292 cells (p<0.05). In addition, IL-17RA, IL
      17RC and act1 siRNA significantly blocked IL-17A-induced MUC5AC production in
      vitro (p<0.05). CONCLUSION: Our results suggest that IL-17A plays a crucial role
      in stimulating the production of MUC5AC and goblet cell hyperplasia through the
      act1-mediated signaling pathway and may suggest a promising strategy for the
      management of Th17-dominant NP patients.

PMID- 24892825
TI  - Wnt signaling activates Shh signaling in early postnatal intervertebral discs,
      and re-activates Shh signaling in old discs in the mouse.
AB  - Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect
      adjacent vertebrae of the spine. As discs age they become prone to failure, with
      neurological consequences that are often severe. Surgical repair of discs treats
      the result of the disease, which affects as many as one in seven people, rather
      than its cause. An ideal solution would be to repair degenerating discs using the
      mechanisms of their normal differentiation. However, these mechanisms are poorly
      understood. Using the mouse as a model, we previously showed that Shh signaling
      produced by nucleus pulposus cells activates the expression of differentiation
      markers, and cell proliferation, in the postnatal IVD. In the present study, we
      show that canonical Wnt signaling is required for the expression of Shh signaling
      targets in the IVD. We also show that Shh and canonical Wnt signaling pathways
      are down-regulated in adult IVDs. Furthermore, this down-regulation is
      reversible, since re-activation of the Wnt or Shh pathways in older discs can re
      activate molecular markers of the IVD that are lost with age. These data suggest
      that biological treatments targeting Wnt and Shh signaling pathways may be
      feasible as a therapeutic for degenerative disc disease. 

PMID- 24892826
TI  - Diffusion tensor imaging study of white matter damage in chronic meningitis.
AB  - Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most
      common types of chronic meningitis. This study aimed to assess whether chronic
      neuro-psychological sequelae are associated with micro-structure white matter
      (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM
      patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy
      volunteers were evaluated and compared. The clinical relevance of WM integrity
      was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance
      imaging. All of the participants underwent complete medical and neurologic
      examinations, and neuro-psychological testing. Differences in DTI indices
      correlated with the presence of neuro-psychological rating scores and
      cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients
      with CM had more severe cognitive deficits than healthy subjects, especially in
      TBM. There were changes in WM integrity in several limbic regions, including the
      para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus
      pallidus. A decline in WM integrity close to the globus pallidus and anterior
      cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI
      parameters directly correlated with worse cognitive performance on follow-up.
      These correlations suggest that WM alterations may be involved in the
      psychopathology and pathophysiology of co-morbidities. Abnormalities in the
      limbic system and globus pallidus, with their close relationship to the CSF
      space, may be specific biomarkers for disease evaluation. 

PMID- 24892828
TI  - Inbreeding depression in a parasitoid wasp with single-locus complementary sex
      determination.
AB  - Inbreeding and inbreeding depression are key processes in small or isolated
      populations and are therefore central concerns for the management of threatened
      or (re)introduced organisms. Haplodiploid species of the order Hymenoptera have a
      particular status with regard to inbreeding depression. Although recessive
      deleterious alleles that are expressed in males should be purged, an alternative
      form of inbreeding depression exists in species with single-locus complementary
      sex determination (sl-CSD). Under sl-CSD, genetically-related parents have a high
      probability of producing sterile sons instead of fertile daughters. In this
      article, we study inbreeding depression in Venturia canescens (Hymenoptera:
      Ichneumonidae), a parasitoid wasp with sl-CSD. We used a crossing design to
      manipulate relatedness according to three levels: within-family, between-family
      and between-population. For each level, several fitness components were measured
      on parents and female offspring. We found a 20% reduction in egg load at
      emergence for inbred crosses. Inbred crosses also yielded a higher proportion of
      males, as expected in a species with sl-CSD. Mating probability, presence of
      daughters among offspring, body size, symmetry and longevity were unaffected by
      inbreeding. 

PMID- 24892829
TI  - Art in time and space: context modulates the relation between art experience and
      viewing time.
AB  - The experience of art emerges from the interaction of various cognitive and
      affective processes. The unfolding of these processes in time and their relation
      with viewing behavior, however, is still poorly understood. Here we examined the
      effect of context on the relation between the experience of art and viewing time,
      the most basic indicator of viewing behavior. Two groups of participants viewed
      an art exhibition in one of two contexts: one in the museum, the other in the
      laboratory. In both cases viewing time was recorded with a mobile eye tracking
      system. After freely viewing the exhibition, participants rated each artwork on
      liking, interest, understanding, and ambiguity scales. Our results show that
      participants in the museum context liked artworks more, found them more
      interesting, and viewed them longer than those in the laboratory. Analyses with
      mixed effects models revealed that aesthetic appreciation (compounding liking and
      interest), understanding, and ambiguity predicted viewing time for artworks and
      for their corresponding labels. The effect of aesthetic appreciation and
      ambiguity on viewing time was modulated by context: Whereas art appreciation
      tended to predict viewing time better in the laboratory than in museum context,
      the relation between ambiguity and viewing time was positive in the museum and
      negative in the laboratory context. Our results suggest that art museums foster
      an enduring and focused aesthetic experience and demonstrate that context
      modulates the relation between art experience and viewing behavior. 

PMID- 24892830
TI  - HPLC-based activity profiling for antiplasmodial compounds in the traditional
      Indonesian medicinal plant Carica papaya L.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leaf decoctions of Carica papaya have been
      traditionally used in some parts of Indonesia to treat and prevent malaria. Leaf
      extracts and fraction have been previously shown to possess antiplasmodial
      activity in vitro and in vivo. MATERIALS AND METHODS: Antiplasmodial activity of
      extracts was confirmed and the active fractions in the extract were identified by
      HPLC-based activity profiling, a gradient HPLC fractionation of a single
      injection of the extract, followed by offline bioassay of the obtained
      microfractions. For preparative isolation of compounds, an alkaloidal fraction
      was obtained via adsorption on cationic ion exchange resin. Active compounds were
      purified by HPLC-MS and MPLC-ELSD. Structures were established by HR-ESI-MS and
      NMR spectroscopy. For compounds 5 and 7 absolute configuration was confirmed by
      comparison of experimental and calculated electronic circular dichroism (ECD)
      spectroscopy data, and by X-ray crystallography. Compounds were tested for
      bioactivity in vitro against four parasites (Trypanosoma brucei rhodesiense,
      Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum), and in the
      Plasmodium berghei mouse model. RESULTS: Profiling indicated flavonoids and
      alkaloids in the active time windows. A total of nine compounds were isolated.
      Four were known flavonols--manghaslin, clitorin, rutin, and nicotiflorin. Five
      compounds isolated from the alkaloidal fraction were piperidine alkaloids.
      Compounds 5 and 6 were inactive carpamic acid and methyl carpamate, while three
      alkaloids 7-9 showed high antiplasmodial activity and low cytotoxicity. When
      tested in the Plasmodium berghei mouse model, carpaine (7) did not increase the
      survival time of animals. CONCLUSIONS: The antiplasmodial activity of papaya
      leaves could be linked to alkaloids. Among these, carpaine was highly active and
      selective in vitro. The high in vitro activity could not be substantiated with
      the in vivo murine model. Further investigations are needed to clarify the
      divergence between our negative in vivo results for carpaine, and previous
      reports of in vivo activity with papaya leaf extracts.

PMID- 24892831
TI  - Traditional uses of medicinal plants against malarial disease by the tribal
      communities of Lesser Himalayas-Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is among the most prevalent infectious
      diseases in the developing countries of world. Estimated number of annual malaria
      episodes in Pakistan is 1.5 million, but very little is known about medicinal
      plant species of Pakistan, which have great potential against malarial disease.
      Present study was aimed to document medicinal plant species used by the local
      inhabitants of Lesser Himalayas-Pakistan to treat malaria. MATERIALS AND METHODS:
      Data were collected through interviews, questionnaires and contributor
      observation. A total of 55 informants aged between 25 and 80 years who were
      familiar with malarial disease participated in the survey. RESULTS: A total of 84
      plant species belonging to 69 genera and 50 families were recorded to treat
      malaria. Asteraceae was found as most cited botanical family with (11.9%)
      representation, followed by Lamiaceae (5.9%), Solanaceae and Verbenaceae (4.7%)
      and Violaceae (3.5%) respectively. About 60% of the inhabitants prefer herbal
      treatment by local herbalists or self-treatment with locally available medicinal
      plant species. Of the plants identified during present investigation against
      malaria, Azadirachta indica, Swertia chirayita and Swertia ciliata exhibited
      uppermost frequency of encounter (36.3%) and corresponding PR value 5. About
      67.2% of the botanical taxa are reported for the first time in the treatment of
      malaria. It was observed thatover harvesting is the foremost threat to medicinal
      plant species of the study area. CONCLUSION: Present survey indicates that
      traditional knowledge about the use of plant species against various diseases and
      particularly to treat malaria is in decline. Similarly anthropogenic pressure,
      over exploitation and grazing of the botanical taxa are the major concerns
      regarding medicinal plant biodiversity loss. Frequently utilized plant species
      with significant malarial reduction should be authenticated by in vitro and in
      vivo standard tests.

PMID- 24892832
TI  - Essential oil from Pterodon emarginatus seeds ameliorates experimental autoimmune
      encephalomyelitis by modulating Th1/Treg cell balance.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pterodon emarginatus Vogel is a medicinal plant
      commonly used in Brazilian traditional medicine as a folk therapy due to its
      immunosuppressive, anti-inflammatory, anti-rheumatic, healing, tonic and
      depurative activities. The essential oil (EO) of Pterodon emarginatus is composed
      of volatile aromatic terpenes and phenyl propanoids, mainly, beta-elemene and
      beta-caryophyllene sesquiterpenes. Here we reported the effects and some
      underlying mechanisms of action of EO during murine model of MS, the experimental
      autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: EO (50 and 100 mg/kg)
      was orally administered during the entire period of development of EAE
      (preventive treatment, day 0-25). In vitro and in vivo immunological responses
      were evaluated by ELISA, immunohistochemistry, immunofluorescence and flow
      cytometry. RESULTS: We provide evidence that EO of Pterodon emarginatus (100
      mg/kg, p.o.) significantly attenuates neurological signs and also the development
      of EAE. Furthermore, at the same dose EO consistently inhibited Th1 cell-mediated
      immune response and upregulated Treg response in vitro. Moreover, the EO
      inhibited both microglial activation and expression of iNOS, associated with
      inhibition of axonal demyelization and neuronal death during the development of
      the disease. CONCLUSION: This is the first experimental evidence showing that
      oral administration of EO consistently reduces and limits the severity and
      development of EAE, mainly, through the modulation of Th1/Treg immune balance,
      and might represent a helpful new tool for control immunoinflammatory conditions,
      such as MS.

PMID- 24892833
TI  - Hypoglycemic properties of some preparations and compounds from Artemisia
      ludoviciana Nutt.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ludoviciana, commonly known as
      "estafiate", plays an important role in contemporary Mexico for treating several
      diseases including diabetes. To establish the preclinical efficacy of Artemisia
      ludoviciana as hypoglycemic and/or antihyperglycemic agent using well-known
      animal models. MATERIALS AND METHODS: Acute hypoglycemic as well as oral glucose
      (OGTT) and sucrose (OSTT) tolerance tests were used to demonstrate the value of
      the plant for treating diabetes. An essential oil (EO), an organic extract (OE)
      and an infusion (AE) were assayed in normal and NA-STZ-treated mice. The acute
      toxicity of the three preparations was analyzed by the Lorke method. The infusion
      was subjected to conventional phytochemical study using chromatographic
      conventional procedures. Some of the isolates were evaluated using the same
      pharmacological assays as well as an enzymatic test. The latter was employed to
      assess their potential inhibitory effect on yeast alpha-glucosidase. RESULTS:
      Oral administration of OE to normal mice significantly decreased blood glucose
      level only at the dose of 100 mg/kg; in NA-STZ-mice the hypoglycemic effect was
      observed at the three doses tested (31.6, 100, and 316 mg/kg). The infusion
      reduced significantly, blood sugar levels only in diabetic mice; the best effect
      was observed at the dose of 316 mg/kg. The EO was inactive when evaluated in
      normal mice. Regarding to the antihyperglycemic effect, the best effect was
      observed with the OE, during the OGTT and OSTT in diabetic mice. The infusion
      (AE) showed better effects during the OGTT in both normal and diabetic animals at
      the dose of 100 mg/kg. Finally, the EO was inactive during an OGTT at the three
      doses tested (31.6, 100, and 316 mg/kg) in diabetic mice. In addition, the
      results of AE on the enzymatic test using yeast alpha-glucosidase revealed an
      inhibition of 45%; this finding was consistent with the results obtained with the
      same preparation in vivo during an OSTT. Conventional phytochemical analysis of
      the active AE led to the isolation and characterization of eupatilin (1),
      jaceosidin (2), arglanin (3), salvinine (4), and 3,5-dicaffeoylquinic acid (5).
      Biological testing of 1 and 3 revealed their hypoglycemic effect. The
      hypoglycemic effect of arglanin (3) was attenuated in the presence of nicorandil,
      which suggested that the lactone behaved as an ATP-K+-channel blocker as
      glibenclamide. Salvinine (4) turned out to be a mixed alpha-glucosidase
      inhibitor, while 3 was inactive. CONCLUSIONS: Artemisia ludoviciana preparations
      showed hypoglycemic and antihyperglycemic effects, which could explain its
      effectiveness for treating diabetes in contemporary Mexico. Some of the active
      principles of the plant included compounds 1-5. These compounds seem to be acting
      synergistically on different molecular targets which involved glucose absorption
      and insulin liberation.

PMID- 24892834
TI  - Ethnopharmacological survey of medicinal plants used by traditional health
      practitioners in Thanchi, Bandarban Hill Tracts, Bangladesh.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: There is very limited information regarding
      plants used by traditional healers in Bandarban Hill Tracts (BHT), Bangladesh for
      treating general as well as complex ailments. Current study provides significant
      ethnopharmacological information, both qualitative and quantitative on medical
      plants in BHT. Aim of the study This study aimed to collect, analyze and evaluate
      the rich ethnopharmacologic knowledge on medicinal plants in Thanchi, BHT and
      attempted to identify the important species used in traditional medicine. Further
      analysis was done by comparison of the traditional medicinal use of the plants
      with the available scientific literature data. MATERIALS AND METHODS: The field
      survey was carried out in a period of several years in Thanchi upazilla of
      Bandarban districts, Bangladesh. A total of 53 Traditional Health Practitioners
      (THPs) were interviewed through open-ended and semi structured questionnaire. The
      collected data were analyzed qualitatively and quantitatively. This
      ethnomedicinal knowledge was compared against the available scientific literature
      for reports of related uses and studies of phytochemical compounds responsible
      for respective ailments. RESULTS: A total of 84 species of plants, mostly herbs,
      belonging to 42 families were identified for the treatment of 70 types of
      ailments. These ailments were categorized into 16 categories. Leaves were the
      most frequently used plant parts and juice is the mode of preparation of major
      portions of the plant species. The most common mode of administration was oral
      ingestion and topical application. Informant consensus factor (Fic) values of the
      present study reflected the high agreement in the use of plants in the treatment
      of digestive system and respiratory system disorders among the informants.
      Diseases of the digestive system had highest use-reports and 3 species of plants,
      namely Centella asiatica (L.) Urban. (dysentery), Justicia gendarussa L. (asthma)
      and Ocimum tenuiflorum L. (coughing) had the highest fidelity level (FL) of 100%.
      Clerodendrum viscosum Vent., Achyranthes aspera L and Justicia gendarussa L.
      showed the highest relative importance (RI) value of 1.86. According to use value
      (UV) the most important species were Ocimum tenuiflorum L. (2.24) and Achyranthes
      aspera L. (2.15). CONCLUSION: Priority should be given for further phytochemical
      investigation to plants that scored highest FL, Fic, UV or RI values, as such
      values could be considered as good indicator of prospective plants for
      discovering new drugs. Since knowledge regarding traditional medicine being
      vulnerable day by day so traditional medicine in school curricula should be
      incorporated so that younger people could appreciate its usefulness. Also
      counseling of THPs and gardening of medicinal plants should be taken into
      consideration immediately in order to smooth continuance and extension of
      traditional medical knowledge and practice for ensuring safe and effective
      therapy.

PMID- 24892835
TI  - Number word use in toddlerhood is associated with number recall performance at
      seven years of age.
AB  - Previous studies have shown that verbal working memory and vocabulary acquisition
      are linked in early childhood. However, it is unclear whether acquisition of a
      narrow range of words during toddlerhood may be particularly related to recall of
      the same words later in life. Here we asked whether vocabulary acquisition of
      number words, location and quantifier terms over the first three years of life
      are associated with verbal and visuospatial working memory at seven years. Our
      results demonstrate that children who produced more number words between 20-26
      months and started to produce the number words 1-10 earlier showed greater number
      recall at 7 years of age. This link was specific to numbers and neither extended
      to quantifier and location terms nor verbal and visuospatial working memory
      performance with other stimuli. These findings suggest a category-specific link
      between the mental lexicon of number words and working memory for numbers at an
      early age. 

PMID- 24892837
TI  - Moringa oleifera as a Galactagogue.

PMID- 24892836
TI  - Absence of an intron splicing silencer in porcine Smn1 intron 7 confers immunity
      to the exon skipping mutation in human SMN2.
AB  - Spinal Muscular Atrophy is caused by homozygous loss of SMN1. All patients retain
      at least one copy of SMN2 which produces an identical protein but at lower levels
      due to a silent mutation in exon 7 which results in predominant exclusion of the
      exon. Therapies targeting the splicing of SMN2 exon 7 have been in development
      for several years, and their efficacy has been measured using either in vitro
      cellular assays or in vivo small animal models such as mice. In this study we
      evaluated the potential for constructing a mini-pig animal model by introducing
      minimal changes in the endogenous porcine Smn1 gene to maintain the native
      genomic structure and regulation. We found that while a Smn2-like mutation can be
      introduced in the porcine Smn1 gene and can diminish the function of the ESE, it
      would not recapitulate the splicing pattern seen in human SMN2 due to absence of
      a functional ISS immediately downstream of exon 7. We investigated the ISS region
      and show here that the porcine ISS is inactive due to disruption of a proximal
      hnRNP A1 binding site, while a distal hnRNP A1 binding site remains functional
      but is unable to maintain the functionality of the ISS as a whole. 

PMID- 24892838
TI  - Ticking time bomb? Climate change and Ixodes scapularis.

PMID- 24892839
TI  - A mechanical and electrical transistor structure (METS) with a sub-2 nm nanogap
      for effective voltage scaling.
AB  - A mechanical and electrical transistor structure (METS) is proposed for effective
      voltage scaling. The sub-2 nm nanogap by atomic layer deposition (ALD) without
      stiction and the application of a dielectric with high-permittivity allowed the
      pull-in voltage of sub-2 V, showing the strength of the mechanical actuation that
      is hard to realize in a typical complementary metal-oxide-semiconductor (CMOS)
      transistor. The results are verified by simulation and interpreted by the
      numerical equation. Therefore the METS can pave a new way to make a breakthrough
      to overcome the limits of CMOS technology. 

PMID- 24892840
TI  - New developments in metastatic breast cancer: integrating recent data into
      clinical practice.
AB  - The treatment of metastatic breast cancer continues to be a challenging area for
      medical oncologists. Breast tumors are classified into several groups based on
      immunohistochemistry: those that are estrogen-receptor-positive and human
      epidermal growth factor receptor 2 (HER2)-negative; those that are HER2-positive
      and either estrogen-receptor-positive or estrogen-receptor-negative; and those
      that are negative for the estrogen receptor, progesterone receptor, and HER2
      (known as triple-negative). These biologic factors are an important component of
      the risk assessment and treatment strategy. Management goals for advanced disease
      are to target treatment to the specific biology in a more effective way, and to
      add in targeted agents that may improve the effectiveness of standard therapies,
      such as hormone therapy and chemotherapy. There are several new therapies that
      are changing outcome for patients with metastatic disease, such as eribulin,
      pertuzumab, and ado-trastuzumab emtansine. It is critical to understand the
      appropriate dosing schedules of novel agents and how best to combine them with
      standard therapy. Ongoing clinical trials are evaluating new treatment
      approaches, as well as ways to identify biologic subsets that might benefit from
      particular therapies. Investigational agents include glembatumumab vedotin,
      neratinib, and margetuximab.

PMID- 24892845
TI  - Synthesis, spectroscopy studies, and theoretical calculations of new fluorescent
      probes based on pyrazole containing porphyrins for Zn(II), Cd(II), and Hg(II)
      optical detection.
AB  - New pyrazole-porphyrin conjugates were successfully prepared from a reaction of
      beta-porphyrin-chalcone derivatives with phenylhydrazine in acetic acid followed
      by an oxidative step. This fast and efficient synthetic approach provided the
      expected compounds in yields up to 82%. The sensing ability of the new porphyrin
      pyrazole derivatives to detect the metal ions Ag(+), Na(+), K(+), Mg(2+), Ca(2+),
      Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), and Cr(3+) was studied by
      spectrophotometric and spectrofluorimetric titrations. In the presence of Zn(2+),
      the conjugates exhibit changes in the emission spectra that are desired for a
      ratiometric-type fluoroionophoric detection probe. The studies were extended to
      gas phase, where the pyrazole-porphyrin conjugates show ability to sense metal
      ions with high selectivity toward Cu(2+) and Ag(+), and in poly(methyl
      methacrylate) doped films with promising results for Zn(2+) detection. 

PMID- 24892844
TI  - Centrin3 in trypanosomes maintains the stability of a flagellar inner-arm dynein
      for cell motility.
AB  - Centrin is a conserved component of centrioles in animals and basal bodies in
      flagellated organisms. It also associates with axonemal inner-arm dyneins and
      regulates cell motility, but the underlying mechanism remains elusive. In
      Trypanosoma brucei, three of the five centrins associate with the flagellar basal
      body, but no centrin has been found to regulate flagellar motility. Here we show
      that TbCentrin3 is a flagellar protein and knockdown of TbCentrin3 compromises
      cell motility. Tandem affinity purification followed by mass spectrometry
      identifies an inner-arm dynein, TbIAD5-1, as the TbCentrin3 partner, and
      knockdown of TbIAD5-1 causes similar cell motility defect. Further, we
      demonstrate the interdependence of TbCentrin3 and TbIAD5-1 for maintaining a
      stable complex in the flagellar axoneme. Together, these results identify the
      essential role of TbCentrin3 in cell motility by maintaining the stability of an
      inner-arm dynein in the flagellum, which may be shared by all the centrin
      containing flagellated and ciliated organisms. 

PMID- 24892846
TI  - A methanolic extract of Ganoderma lucidum fruiting body inhibits the growth of a
      gastric cancer cell line and affects cellular autophagy and cell cycle.
AB  - Ganoderma lucidum is one of the most extensively studied mushrooms as a
      functional food and as a chemopreventive agent due to its recognized medicinal
      properties. Some G. lucidum extracts have shown promising antitumor potential. In
      this study, the bioactive properties of various extracts of G. lucidum, from both
      the fruiting body and the spores, were investigated. The most potent extract
      identified was the methanolic fruiting body extract, which inhibited the growth
      of a gastric cancer cell line (AGS) by interfering with cellular autophagy and
      cell cycle. 

PMID- 24892847
TI  - The macrophage A2B adenosine receptor regulates tissue insulin sensitivity.
AB  - High fat diet (HFD)-induced type 2 diabetes continues to be an epidemic with
      significant risk for various pathologies. Previously, we identified the A2b
      adenosine receptor (A2bAR), an established regulator of inflammation, as a
      regulator of HFD-induced insulin resistance. In particular, HFD was associated
      with vast upregulation of liver A2bAR in control mice, and while mice lacking
      this receptor showed augmented liver inflammation and tissue insulin resistance.
      As the A2bAR is expressed in different tissues, here, we provide the first lead
      to cellular mechanism by demonstrating that the receptor's influence on tissue
      insulin sensitivity is mediated via its expression in macrophages. This was shown
      using a newly generated transgenic mouse model expressing the A2bAR gene in the
      macrophage lineage on an otherwise A2bAR null background. Reinstatement of
      macrophage A2bAR expression in A2bAR null mice fed HFD restored insulin tolerance
      and tissue insulin signaling to the level of control mice. The molecular
      mechanism for this effect involves A2bAR-mediated changes in cyclic adenosine
      monophosphate in macrophages, reducing the expression and release of inflammatory
      cytokines, which downregulate insulin receptor-2. Thus, our results illustrate
      that macrophage A2bAR signaling is needed and sufficient for relaying the
      protective effect of the A2bAR against HFD-induced tissue inflammation and
      insulin resistance in mice. 

PMID- 24892848
TI  - Non-multidrug-resistant, methicillin-resistant Staphylococcus aureus in a
      neonatal unit.
AB  - BACKGROUND: In the last decade, non-multiresistant methicillin-resistant
      Staphylococcus aureus (NM-MRSA) has been described as an important agent in
      bloodstream infections in our hospital. METHODS: This prospective cohort study,
      conducted from February 2009 through January 2010 in the neonatal unit, evaluated
      403 newborns (NB), their 382 mothers and 148 health care workers (HCW). RESULTS:
      Approximately 217 NB (54%), 187 mothers (48%) and 87 HCW (59%) were colonized by
      S. aureus (SA). MRSA colonization was greater among NB (15%) than mothers (4.7%)
      and HCW (3.4%). Although mother-to-NB transmission occurred, in most cases
      mothers were not responsible for NB colonization. There were 2 predominant PFGE
      patterns among the NB and some mothers and HCW became colonized by them. Factors
      significantly associated with MRSA carriage by NB were lower level of maternal
      schooling (risk factor: odds ratio: 2.99; 95% confidence interval: 1.10-8.07) and
      maternal rhinosinusitis (protective factor: odds ratio: 0.33; 95% confidence
      interval:0.12-0.88). Among NB who remained hospitalized for more than 72 hours,
      breast feeding was protective (odds ratio: 0.22; 95% confidence interval: 0.05
      0.98). All the isolates were NM-MRSA, carried few virulence factors and SCCmec
      types IVa and type IVd predominated. CONCLUSIONS: Although there were no cases of
      infection, nosocomial transmission of MRSA clearly occurred in the neonatal unit,
      and this highlights the need for infection control practices such as hand hygiene
      to prevent cross-dissemination. Other healthcare practices, which are very basic
      but also ample in scope, may play a role, such as general education of women and
      breast feeding.

PMID- 24892849
TI  - Micafungin in premature and non-premature infants: a systematic review of 9
      clinical trials.
AB  - BACKGROUND: Invasive fungal infections cause excessive morbidity and mortality in
      premature neonates and severely ill infants. METHODS: Safety and efficacy
      outcomes of micafungin were compared between prematurely and non-prematurely born
      infants <2 years of age. Data were obtained from all completed phase I-III
      clinical trials with micafungin that had enrolled infants (<2 years of age) that
      were listed in the Astellas Clinical Study Database. Demographics, adverse
      events, hepatic function tests and treatment success data were extracted and
      validated by the Astellas biostatistical group for all micafungin-treated
      patients, <2 years of age, using the unique patient identifier. RESULTS: One
      hundred and sixteen patients included in 9 clinical trials, 48% premature [birth
      weight (BW) <2500 g and/or gestational age <37 weeks], 52% non-premature,
      received >= 1 dose of micafungin. Among premature patients, 14.5% were low BW
      (1500-2499 g), 36.4% very low BW (1000-1499 g) and 49.1% extremely low BW (<1000
      g). Ninety patients (78%) completed the studies; 13 [11% (4 premature)] died.
      Significantly more non-premature than premature patients discontinued treatment
      (P = 0.003). Treatment-related adverse events were recorded in 23% of patients
      with no difference between groups. More extremely low BW (n = 4, 15%) and very
      low BW (n = 8, 40%) infants experienced treatment-related adverse events than low
      BW (n = 0) and there was no relation to micafungin dose or duration. For a
      subgroup of 30 patients with invasive candidiasis, treatment success was achieved
      in 73% in both premature and non-premature groups. Prophylaxis was successful in
      4/5 non-premature hematopoietic stem cell transplant patients. CONCLUSION:
      Micafungin has a safe profile in premature and non-premature infants with
      substantial efficacy.

PMID- 24892850
TI  - Candida speciation, antifungal treatment and adverse events in pediatric invasive
      candidiasis: results from 441 infections in a prospective, multi-national study.
AB  - A multi-national prospective study of pediatric patients with invasive
      candidiasis between August 2007 and September 2012 was performed and included 441
      infections. Variation in infecting Candida species and antifungals used was noted
      between US and non-US sites. Antifungal-associated adverse events were most
      common with polyene use. 

PMID- 24892851
TI  - Clinical and laboratory characteristics of central nervous system herpes simplex
      virus infection in neonates and young infants.
AB  - We reviewed the characteristics of infants <3 months of age with central nervous
      system herpes simplex virus infection at our institution. Twenty-six cases were
      identified. The age range was 4-73 days. Most infants presented with fever,
      seizure activity and skin lesions. The blood herpes simplex virus polymerase
      chain reaction was positive in 91% of patients tested. Suppressive oral acyclovir
      therapy was likely helpful in preventing disease recurrence. 

PMID- 24892853
TI  - Picture naming and verbal fluency in children with cochlear implants.
AB  - PURPOSE: In the present study, the authors examined lexical naming in children
      with cochlear implants (CIs). The goal was to determine whether children with CIs
      have deficits in lexical access and organization as revealed through reaction
      time in picture-naming and verbal fluency (VF) experiments. METHOD: Children with
      CIs (n = 20, ages 7-10) were compared with 20 children with normal hearing (NH)
      matched for age and nonverbal IQ. Lexical abilities were examined using two
      naming tasks: a timed picture-naming task and a phonological and semantic VF
      naming task. Picture naming taps into lexical access capabilities and the VF task
      elucidates lexical organization. RESULTS: No group differences were found between
      children with CIs and children with NH on the timed picture-naming task. Children
      with CIs generated significantly fewer words than the children with NH on the VF
      tasks. Larger group differences were found for the phonological VF task compared
      with the semantic VF task. CONCLUSIONS: Limited early linguistic and auditory
      experiences may affect lexical representations and organization (lexical-semantic
      connections) in school-age children with hearing loss who use CIs. Further
      analyses and studies should continue to examine these underlying linguistic
      deficits. The present results suggest a need to emphasize not only increasing the
      size of children's vocabularies during therapy, but also expanding and increasing
      the semantic and phonological richness of their lexical representations.

PMID- 24892854
TI  - Peroxidation of C-H bonds adjacent to an amide nitrogen atom under mild
      conditions.
AB  - Under mild conditions, the oxidative functionalization of C-H bonds adjacent to
      an amide nitrogen atom was achieved. tert-Butylperoxyamido acetal was obtained in
      high yields and could be further converted into alpha-substituted amides by
      treatment with Grignard reagents. 

PMID- 24892852
TI  - HIV-1 subtype A gag variability and epitope evolution.
AB  - OBJECTIVE: The aim of this study was to examine the course of time-dependent
      evolution of HIV-1 subtype A on a global level, especially with respect to the
      dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1
      subtype A gag sequences representing a timeline from 1985 through 2010, and 19
      different countries in Africa, Europe and Asia. The phylogenetic relationship of
      subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood
      tree and Bayesian Skyline plot, genomic variability was measured in terms of G ->
      A substitutions and Shannon entropy, and the time-dependent evolution of HIV
      subtype A gag epitopes was examined. Finally, to confirm observations on globally
      reported HIV subtype A sequences, we analysed the gag epitope data from our
      Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope
      variability and HLA restriction profiles of gag epitopes were examined. RESULTS:
      The most recent common ancestor of the HIV subtype A epidemic was estimated to be
      1956 +/- 1. A period of exponential growth began about 1980 and lasted for
      approximately 7 years, stabilized for 15 years, declined for 2-3 years, then
      stabilized again from about 2004. During the course of evolution, a gradual
      increase in genomic variability was observed that peaked in 2005-2010. We
      observed that the number of point mutations and novel epitopes in gag also peaked
      concurrently during 2005-2010. CONCLUSION: It appears that as the HIV subtype A
      epidemic spread globally, changing population immunogenetic pressures may have
      played a role in steering immune-evolution of this subtype in new directions.
      This trend is apparent in the genomic variability and epitope diversity of HIV-1
      subtype A gag sequences.

PMID- 24892857
TI  - "Something must be done!": public health nursing education in the United States
      from 1900 to 1950.
AB  - This article examines public health nursing (PHN) education in the United States
      from 1900 to 1950. Following establishment of district nursing and the Henry
      Street Settlement in the late 1800s, nurses worked with families and communities
      in schools, homes, and with immigrant populations in tenements of industrialized
      cities. By the early 1900s, PHN leaders recognized that graduates needed broader
      education than provided by hospital training schools to prepare nurses to address
      social conditions and promote health and hygiene for populations. Current themes
      in professional nursing, such as social determinants of health, have their roots
      in early discourse about PHN education. 

PMID- 24892859
TI  - No communicable diseases this month: public health nursing at the Colorado River
      Relocation Center, 1942-1945.
AB  - In the name of public safety, the US government forcibly removed more than 110
      000 Japanese Americans from their homes along the West Coast of the United States
      during World War II. Incarcerated in crude barracks located in remote locations,
      Japanese Americans were suddenly required to share laundry facilities, toilets,
      showers, and mess halls with hundreds of likewise incarcerated Japanese
      Americans. With conditions ripe for spreading communicable disease, public health
      nurses relied on health promotion techniques of the time to prevent epidemic
      outbreaks of diseases such as measles, polio, and tuberculosis. 

PMID- 24892858
TI  - The Fort Lewis maternity care project: a pioneering program for enlisted military
      families in a Prewar Washington State Community.
AB  - The Fort Lewis maternity project begun in Tacoma, Washington in 1941, was
      considered a pioneering project that met the identified maternal/child health
      care needs of enlisted military families. From the outset, local medical leaders
      as well as Children's Bureau advisors intended that the project would provide
      physician-managed pregnancy as well as hospital births and that public health
      nursing would play a critical role in this maternal/child initiative. The project
      proved so successful that the model of care established under this program was
      reinterpreted to meet similar needs for military families in other states as
      America entered World War II. 

PMID- 24892861
TI  - Lessons in community health activism: the maternity care coalition, 1970-1990.
AB  - This study employed historical methodologies to explore the means through which
      the Maternity Care Coalition used grassroots activism to dismantle the power
      structures and other obstacles that contributed to high infant mortality rates in
      Philadelphia's health districts 5 and 6 during the 1980s. Infant mortality within
      the black community has been a persistent phenomenon in the United States.
      Refusing to accept poverty as a major determinant of infant mortality within
      marginalized populations of women, activists during the 1980s harnessed momentum
      from a postcivil rights context and sought alternative methods toward change and
      improvement of infant mortality rates. 

PMID- 24892860
TI  - "Civil unrest does not stop ovulation": women's prenatal and family planning
      services in a 1960s Detroit neighborhood clinic.
AB  - In 1965, Nancy Milio established a prenatal and family planning clinic in
      Detroit, Michigan, to address health disparities and limited access to care among
      low-income, African American, urban women. Women's health disparities persist
      today nationally and internationally. Using historical methods, this research
      analyzes how Milio provided women's health services in the context of the social
      and political environment. Milio empowered neighborhood women to direct, plan,
      and participate in the care they received. Successful methods to address
      disparities in access to family and planning and prenatal care should include
      empowered participation from the women these programs are intending to serve. 

PMID- 24892862
TI  - Women, religion, and maternal health care in Ghana, 1945-2000.
AB  - This article documents the historical factors that led to shifts in mission work
      toward a greater emphasis on community health for the poor and most vulnerable of
      society in sub-Saharan Africa after 1945. Using the example of the Medical
      Mission Sisters from Philadelphia, Pennsylvania, and their work in Ghana, we
      challenge the conventional narrative of medical missions as agents of
      imperialism. We assert that missions-particularly those run by Catholic sister
      physicians, nurses, and midwives-have changed over time and that those changes
      have been beneficial to the expansion of community health, particularly in the
      area of improvement of maternal care. 

PMID- 24892863
TI  - Resistance and religion: health care in Uganda, 1971-1979.
AB  - This article situates women's roles in community health care during violence in
      Uganda in the 1970s. It examines the lived reality of Catholic missionary sister
      nurses, midwives, and physicians on the ground where sisters administered health
      care to local communities. The goal is to examine how religious women worked with
      local individuals and families in community health during periods of violence and
      war. Catholic sisters claimed to be apolitical, yet their mission work widened to
      include political issues. As they saw local Ugandans threatened, sisters engaged
      in political activities by their identification with and protection of "their
      people." 

PMID- 24892864
TI  - From the trunk of a Volkswagen beetle: a mobile nursing clinic in Appalachia.
AB  - Access to health care has been a factor for patients living in isolated mountain
      regions. The Frontier Nursing service was a pioneer in reaching those patients
      living in the most remote regions of Appalachia. Geography, demographics, and
      culture present obstacles for rural residents and health care providers. This
      article identifies and describes the roles nurses and nurse practitioners played
      in caring for Appalachian families through a roving Health Wagon in the 1980s and
      1990s in Southwest Virginia. Family nurse practitioner Sister Bernadette Kenny
      was instrumental in bringing care on wheels to rural residents living in the
      Appalachian mountainous region of southwest Virginia. 

PMID- 24892865
TI  - Biochemical and molecular characterization of barley plastidial ADP-glucose
      transporter (HvBT1).
AB  - In cereals, ADP-glucose transporter protein plays an important role in starch
      biosynthesis. It acts as a main gate for the transport of ADP-glucose, the main
      precursor for starch biosynthesis during grain filling, from the cytosol into the
      amyloplasts of endospermic cells. In this study, we have shed some light on the
      molecular and biochemical characteristics of barley plastidial ADP-glucose
      transporter, HvBT1. Phylogenetic analysis of several BT1 homologues revealed that
      BT1 homologues are divided into two distinct groups. The HvBT1 is assigned to the
      group that represents BT homologues from monocotyledonous species. Some members
      of this group mainly work as nucleotide sugar transporters. Southern blot
      analysis showed the presence of a single copy of HvBT1 in barley genome. Gene
      expression analysis indicated that HvBT1 is mainly expressed in endospermic cells
      during grain filling; however, low level of its expression was detected in the
      autotrophic tissues, suggesting the possible role of HvBT1 in autotrophic
      tissues. The cellular and subcellular localization of HvBT1 provided additional
      evidence that HvBT1 targets the amyloplast membrane of the endospermic cells.
      Biochemical characterization of HvBT1 using E. coli system revealed that HvBT1 is
      able to transport ADP-glucose into E. coli cells with an affinity of 614.5 uM and
      in counter exchange of ADP with an affinity of 334.7 uM. The study also showed
      that AMP is another possible exchange substrate. The effect of non-labeled ADP
      glucose and ADP on the uptake rate of [alpha-32P] ADP-glucose indicated the
      substrate specificity of HvBT1 for ADP-glucose and ADP. 

PMID- 24892867
TI  - Predictive role of polymerase chain reaction in the early diagnosis of congenital
      Trypanosoma cruzi infection.
AB  - The efficacy of specific chemotherapy in congenital Chagas disease before the
      first year of life ranges between 90 and 100%. Between this age and 15 years of
      age, the efficacy decreases to around 60%. Therefore, early infection detection
      is a priority in vertical transmission. The aim of this work was to assess
      whether polymerase chain reaction (PCR) plays a predictive role in the diagnosis
      of congenital Chagas disease as compared to conventional parasitological and
      serological methods. To this end, we studied a total of 468 children born to
      Trypanosoma cruzi seroreactive mothers came from Argentina, Bolivia and Paraguay,
      who lived in the city of Buenos Aires and suburban areas (Argentina), a non
      endemic area of this country. These children were assessed by PCR from 2004 to
      2009 with the specific primers Tcz1 and Tcz2, and 121 and 122. PCR allowed
      detecting 49 T. cruzi-positive children. Eight of these 49 children were excluded
      from the analysis: six because they did not complete follow-up and two because
      the first control was performed after 12 months of age. Parasitological methods
      allowed detecting 25 positive children, 7 of whom had been earlier diagnosed by
      PCR (1.53+/-2.00 vs. 6.71+/-1.46 months; p=0.0002). Serological methods allowed
      detecting 16 positive children, 12 of whom had been earlier diagnosed by PCR
      (1.46+/-1.48 vs. 11.77+/-4.40 months; p<0.0001). None of the children negative by
      PCR was positive by serological or parasitological methods. This study shows that
      PCR allows early diagnosis in congenital Chagas disease. At present, an early
      positive PCR is not indicative for treatment. However, a positive PCR would alert
      the health system to search only those infected infants diagnosed by early PCR
      and thus generate greater efficiency in the diagnosis and treatment of congenital
      T. cruzi infection. 

PMID- 24892866
TI  - Arthroscopic assessment of stifle synovitis in dogs with cranial cruciate
      ligament rupture.
AB  - Cranial cruciate ligament rupture (CR) is a degenerative condition in dogs that
      typically has a non-contact mechanism. Subsequent contralateral rupture often
      develops in dogs with unilateral CR. Synovitis severity is an important factor
      that promotes ligament degradation. Consequently, we wished to evaluate the
      utility of arthroscopy for assessment of stifle synovitis in dogs with CR.
      Herein, we report results of a prospective study of 27 dogs with unilateral CR
      and bilateral radiographic osteoarthritis. Arthroscopic images and synovial
      biopsies from the lateral and medial joint pouches were obtained bilaterally and
      graded for synovial hypertrophy, vascularity, and synovitis. Synovial tartrate
      resistant acid phosphatase-positive (TRAP+) macrophages, CD3(+) T lymphocytes,
      Factor VIII+ blood vessels, and synovial intima thickness were quantified
      histologically and related to arthroscopic observations. Risk of subsequent
      contralateral CR was examined using survival analysis. We found that arthroscopic
      scores were increased in the index stifle, compared with the contralateral stifle
      (p<0.05). Numbers of CD3+ T lymphocytes (SR = 0.50, p<0.05) and TRAP+ cells in
      joint pouches (SR = 0.59, p<0.01) were correlated between joint pairs.
      Arthroscopic grading of vascularity and synovitis was correlated with number
      density of Factor VIII+ vessels (SR>0.34, p<0.05). Arthroscopic grading of villus
      hypertrophy correlated with numbers of CD3(+) T lymphocytes (SR = 0.34, p<0.05).
      Synovial intima thickness was correlated with arthroscopic hypertrophy,
      vascularity, and synovitis (SR>0.31, p<0.05). Strong intra-observer and moderate
      inter-observer agreement for arthroscopic scoring was found. Dog age and
      arthroscopic vascularity significantly influenced risk of contralateral CR over
      time. We conclude that arthroscopic grading of synovitis is a precise tool that
      correlates with histologic synovitis. Arthroscopy is useful for assessment of
      stifle synovitis in client-owned dogs, and could be used in longitudinal clinical
      trials to monitor synovial responses to disease-modifying therapy.

PMID- 24892868
TI  - ["What will Change and what will Stay" - in Memory of Michael von Rad (24.9.1939 
      27.4.2014)].

PMID- 24892870
TI  - [Reports from the German College of Psychosomatic Medicine].

PMID- 24892869
TI  - [Transgender, transsexualism and gender dysphoria: current developments in
      diagnostics and health care].

PMID- 24892872
TI  - Dimensionality of burden in Alzheimer caregivers: confirmatory factor analysis
      and correlates of the Zarit Burden interview.
AB  - ABSTRACT Background: To investigate dimensions of caregiver burden through factor
      analysis of the Zarit Burden Interview (ZBI), and to examine predictors of
      different dimensions of burden. Methods: Confirmatory factor analyses were
      performed on 395 Hong Kong Chinese Alzheimer caregivers to examine whether
      several proposed factor structures fit the data well. Subsequently, participants
      were split into two roughly equal subsamples, for the purpose of identifying the
      most optimal factor structure through exploratory factor analysis in Sample A (n
      = 183) and an independent verification through confirmatory factor analysis in
      Sample B (n = 212). ZBI subscales representing the established factors were
      correlated with caregiver and care-recipient variables known to be associated
      with burden. Results: Confirmatory factor analyses showed that factor models
      reported elsewhere did not fit the data well. Subsequently, exploratory factor
      analysis in Sample A suggested a 4-factor structure. After dropping three items
      due to poor factor loadings, the 4-factor structure was found to fit the data
      moderately well in Sample B. The four factors tapped personal strain, captivity,
      self-criticism, and loss of control. However, self-criticism was basically
      unrelated to the other three factors and showed a rather different pattern of
      correlations with caregiver and care-recipient variables. Self-criticism was more
      common among child caregivers and those who did not live with the care-recipient
      and was less involved in day-to-day care, yet feeling obligated and close to the
      care-recipient. Conclusions: The dimensions of caregiver burden may be culturally
      specific. More research is needed to examine cultural considerations in measuring
      caregiver burden.

PMID- 24892871
TI  - Identification of T. gondii myosin light chain-1 as a direct target of
      TachypleginA-2, a small-molecule inhibitor of parasite motility and invasion.
AB  - Motility of the protozoan parasite Toxoplasma gondii plays an important role in
      the parasite's life cycle and virulence within animal and human hosts. Motility
      is driven by a myosin motor complex that is highly conserved across the Phylum
      Apicomplexa. Two key components of this complex are the class XIV unconventional
      myosin, TgMyoA, and its associated light chain, TgMLC1. We previously showed that
      treatment of parasites with a small-molecule inhibitor of T. gondii invasion and
      motility, tachypleginA, induces an electrophoretic mobility shift of TgMLC1 that
      is associated with decreased myosin motor activity. However, the direct target(s)
      of tachypleginA and the molecular basis of the compound-induced TgMLC1
      modification were unknown. We show here by "click" chemistry labelling that
      TgMLC1 is a direct and covalent target of an alkyne-derivatized analogue of
      tachypleginA. We also show that this analogue can covalently bind to model thiol
      substrates. The electrophoretic mobility shift induced by another structural
      analogue, tachypleginA-2, was associated with the formation of a 225.118 Da
      adduct on S57 and/or C58, and treatment with deuterated tachypleginA-2 confirmed
      that the adduct was derived from the compound itself. Recombinant TgMLC1
      containing a C58S mutation (but not S57A) was refractory to click labelling and
      no longer exhibited a mobility shift in response to compound treatment,
      identifying C58 as the site of compound binding on TgMLC1. Finally, a knock-in
      parasite line expressing the C58S mutation showed decreased sensitivity to
      compound treatment in a quantitative 3D motility assay. These data strongly
      support a model in which tachypleginA and its analogues inhibit the motility of
      T. gondii by binding directly and covalently to C58 of TgMLC1, thereby causing a
      decrease in the activity of the parasite's myosin motor. 

PMID- 24892873
TI  - The well-being 5: development and validation of a diagnostic instrument to
      improve population well-being.
AB  - Building upon extensive research from 2 validated well-being instruments, the
      objective of this research was to develop and validate a comprehensive and
      actionable well-being instrument that informs and facilitates improvement of well
      being for individuals, communities, and nations. The goals of the measure were
      comprehensiveness, validity and reliability, significant relationships with
      health and performance outcomes, and diagnostic capability for intervention. For
      measure development and validation, questions from the Well-being Assessment and
      Wellbeing Finder were simultaneously administered as a test item pool to over
      13,000 individuals across 3 independent samples. Exploratory factor analysis was
      conducted on a random selection from the first sample and confirmed in the other
      samples. Further evidence of validity was established through correlations to the
      established well-being scores from the Well-Being Assessment and Wellbeing
      Finder, and individual outcomes capturing health care utilization and
      productivity. Results showed the Well-Being 5 score comprehensively captures the
      known constructs within well-being, demonstrates good reliability and validity,
      significantly relates to health and performance outcomes, is diagnostic and
      informative for intervention, and can track and compare well-being over time and
      across groups. With this tool, well-being deficiencies within a population can be
      effectively identified, prioritized, and addressed, yielding the potential for
      substantial improvements to the health status, performance, and quality of life
      for individuals and cost savings for stakeholders.

PMID- 24892874
TI  - Road safety impact of Ontario street racing and stunt driving law.
AB  - OBJECTIVE: The purpose of this study was to conduct a process and outcome
      evaluation of the deterrent impact of Ontario's street racing and stunt driving
      legislation which came into effect on September 30, 2007, on collision casualties
      defined as injuries and fatalities. It was hypothesized that because males,
      especially young ones, are much more likely to engage in speeding, street racing
      and stunt driving, the new law would have more impact in reducing speeding
      related collision casualties in males when compared to females. METHODS:
      Interrupted time series analysis with ARIMA modelling was applied to the monthly
      speeding-related collision casualties in Ontario for the period of January 1,
      2002 to December 31, 2010, separately for young male drivers 16-25 years of age
      (primary intervention group), mature male drivers 26-65 years of age (secondary
      intervention group), young female drivers 16-25 years of age (primary comparison
      group) and mature female drivers 26-65 years of age (secondary comparison group).
      A covariate adjustment using non-speeding casualties was included. RESULTS: A
      significant intervention effect was found for young male drivers with, on
      average, 58 fewer collision casualties per month, but not for mature male
      drivers, when non-speeding casualties were controlled for. No corresponding
      effect was observed in either comparison (females) group. CONCLUSION: These
      findings indicate a reduction in speeding-related casualties among young males of
      58 fewer casualties per month subsequent to the introduction of Ontario's street
      racing and stunt driving legislation and suggest the presence of a general
      deterrent effect.

PMID- 24892875
TI  - Evaluation of a simulation-based surrogate safety metric.
AB  - The development of surrogate safety measures is essential due to the problems of
      availability and quality of historical crash data. The Aggregate Conflict
      Propensity Metric (ACPM) is a surrogate metric recently proposed and it is based
      on conflict studies and traffic simulations. ACPM is expected to be capable of
      assessing the relative safety levels of traffic facilities and/or treatments in
      order to help traffic engineers to select appropriate treatments based on traffic
      safety estimates. This paper presents three experimental tests conducted to
      evaluate the reliability of ACPM. In each test, ACPM is compared to a traditional
      conflict indicator in terms of identifying and ranking safety of traffic
      conditions under various traffic volumes based on traffic simulations. ACPM shows
      its strength and reliability in all three tests, as it provides results highly
      consistent with the Highway Safety Manual. The experimental tests indicate that
      ACPM is a promising surrogate safety measure that can appropriately identify
      relative safety among traffic treatments and/or facilities and provide traffic
      engineers with useful information on potential safety impact. 

PMID- 24892876
TI  - Safety propensity index for signalized and unsignalized intersections:
      exploration and assessment.
AB  - The objective of this study is to develop a safety propensity index (SPI) for
      both signalized and unsignalized intersections. Through the use of a structural
      equation modelling (SEM) approach safety is quantified in terms of multiple
      endogenous variables and related to various dimensions of exogenous variables.
      The singular valued SPI allows for identification of relationships between
      variables and lends itself well to a comparative analysis between models. The
      data provided by the Highway Safety Information System (HSIS) for the California
      transportation network was utilized for analysis. In total 22,422 collisions at
      unsignalized intersections and 20,215 collisions at signalized intersections
      (occurring between 2006 and 2010) were considered in the final models. The main
      benefits of the approach and the subsequent development of an SPI are (1) the
      identification of pertinent variables that effect safety at both intersection
      types, (2) the identification of similarities and differences at both types of
      intersections through model comparison, and (3) the quantification of safety in
      the form of an index such that a ranking system can be developed. If further
      developed, the adopted methodology may assist in safety related decision making
      and policy analysis. 

PMID- 24892877
TI  - A rapidly modulated multifocal detection scheme for parallel acquisition of Raman
      spectra from a 2-D focal array.
AB  - We report the development of a rapidly modulated multifocal detection scheme that
      enables full Raman spectra (~500-2000 cm(-1)) from a 2-D focal array to be
      acquired simultaneously. A spatial light modulator splits a laser beam to
      generate an m * n multifocal array. Raman signals generated within each focus are
      projected simultaneously into a spectrometer and imaged onto a TE-cooled CCD
      camera. A shuttering system using different masks is constructed to collect the
      superimposed Raman spectra of different multifocal patterns. The individual Raman
      spectrum from each focus is then retrieved from the superimposed spectra with no
      crosstalk using a postacquisition data processing algorithm. This system is
      expected to significantly improve the speed of current Raman-based instruments
      such as laser tweezers Raman spectroscopy and hyperspectral Raman imaging.

PMID- 24892878
TI  - Toe photoplethysmographic monitor, a promising noninvasive technique for tracking
      systolic blood pressure trends beat-to-beat.
AB  - The call for early detection of hypotension creates a heavy demand for new
      methods that can monitor trends in blood pressure (BP) levels continuously and
      noninvasively. Photoplethysmography (PPG) is widely used in hemodynamic analysis.
      We assessed the feasibility of toe PPG in tracing BP trends using BP readings
      obtained by standard intermittent noninvasive BP measurements from the arm of a
      patient with severe hypoxic-ischemic brain injury. We demonstrated that an
      attenuated or inversed dicrotic wave of toe PPG is predictive of BP trends, and
      this method could be applicable for the continuous noninvasive monitoring of
      systolic BP at a beat-by-beat basis.

PMID- 24892879
TI  - Invasive validation of the Complior Analyse in the assessment of central artery
      pressure curves: a methodological study.
AB  - INTRODUCTION: Arteries are the target, the place, and the common denominator of
      cardiovascular diseases; hence, study of arterial function is of greatest
      importance in clinical practice. The aim of this study was to evaluate the
      accuracy of carotid pulse wave analysis using the new version of the Complior
      device--the Complior Analyse. METHODS AND RESULTS: This was a cross-sectional
      study that included 15 patients (seven women), mean age 62.07+/-10.59 years,
      referenced for cardiac catheterization. Pressure curves were obtained
      simultaneously in the ascending aorta (invasively) and in the right common
      carotid artery (using the Complior Analyse). Mean central arterial pressures,
      augmentation indexes, and wave morphology obtained using both methods were
      compared. A good concordance between methods was obtained for all the parameters
      measured, with intraclass correlation coefficients above 0.9. Bland-Altman
      analysis also indicated a good accuracy profile of the Complior device, with
      small mean differences observed for all parameters and most values confined
      within 2 SD of the mean difference. This was further confirmed by the strong
      Pearson correlation coefficients, with r2 coefficients above 0.92 for all the
      variables studied. The correlations observed were independent of sex, age,
      arterial pressure, and BMI. CONCLUSION: The results presented and available
      research clearly indicate that the Complior Analyse device measures carotid
      pressure waves accurately; therefore, it is a simple and reliable noninvasive
      alternative for pressure wave analysis.

PMID- 24892880
TI  - Quality of blood pressure phenotype in the Nigerian Population Research on
      Environment Gene and Health.
AB  - OBJECTIVE: In the ongoing Nigerian Population Research on Environment Gene and
      Health (NIPREGH), we are applying standardized epidemiologic methods to determine
      cardiovascular phenotypes including blood pressure (BP) among adult Black
      Africans of Nigerian origin. We present the quality control of the conventionally
      measured BP. PARTICIPANTS AND METHODS: BP observers were trained for 1 month on
      BP measurement at commencement of the project and were retrained for 2 weeks 4
      months later. The observers measured BP five times consecutively on participants
      according to the existing guidelines using a mercury sphygmomanometer. Five
      criteria - the percentage of identical readings, end digit preference, number
      preference, odd BP readings and expected progressive reduction from the first to
      the fifth reading - were used to assess the quality of BP phenotype. RESULTS: As
      of 20 November 2013, a total of 1600 (800 each of systolic and diastolic BP)
      readings obtained from 160 participants were available for analysis. A total of
      175 (21.9%) systolic and 160 (20%) diastolic readings were identical. Three
      (0.002%) of the 1600 BP readings were odd and 433 (27.1%) ended on a 0 (expected
      20%). Per month analysis of digit preference indicates that the observers had no
      significant preference for any digit for the fourth, fifth and sixth month of the
      study (P>0.05). Systolic BP decreased significantly from the first reading to the
      fifth reading (P for trend<0.05), whereas the diastolic BP showed a
      nonsignificant trend towards reduction (P for trend>0.05). CONCLUSION: Inclusion
      of the quality assurance procedures for BP measurement immediately from the
      commencement of NIPREGH and the repeated training for the BP observers yield a
      high quality BP phenotype.

PMID- 24892881
TI  - Serum uric acid and arterial stiffness in hypertensive chronic kidney disease
      patients: sex-specific variations.
AB  - OBJECTIVE: Hyperuricemia and arterial stiffness are associated with increased
      cardiovascular risk. The specific relationship between arterial stiffness and
      serum uric acid (SUA) in chronic kidney disease (CKD) patients has not been
      investigated. We investigated whether the SUA level is associated with arterial
      stiffness in hypertensive CKD patients. MATERIALS AND METHODS: This study had a
      single-center, cross-sectional design. A total of 339 hypertensive CKD patients
      (female/male=192/147, mean age 57.9+/-13.9 years) were recruited. Arterial
      stiffness was assessed by pulse wave velocity (PWV) and augmentation index
      adjusted for heart rate (AIx@75). RESULTS: SUA was correlated negatively with
      night-time wave reflection magnitude (P=0.015), 24-h AIx@75 (P<0.0001), daytime
      AIx@75 (P<0.0001), and night-time AIx@75 (P=0.014), and was correlated positively
      with 24-h PWV (P<0.0001), daytime PWV (P<0.0001), and night-time PWV (P<0.0001).
      SUA was correlated negatively with 24-h AIx@75 (P=0.024), daytime AIx@75
      (P=0.023), and night-time AIx@75 (P=0.047) in men, whereas SUA was correlated
      positively with 24-h PWV (P<0.0001), daytime PWV (P<0.0001), and night-time PWV
      (P<0.0001) in women. In adjusted analysis, SUA was associated independently with
      AIx@75, but not with PWV. In sex-specific unadjusted analysis, SUA was associated
      significantly with PWV only in women, which lost significance in adjusted
      analysis. SUA was associated significantly with AIx@75 only in men, which
      remained significant after adjustment for confounders. CONCLUSION: In
      hypertensive CKD patients, SUA was correlated with the two indices of arterial
      stiffness, PWV and AIx@75, with sex-specific variations. However, SUA was
      associated independently with only AIx@75, but not with PWV, in the entire
      patient population and only in men.

PMID- 24892882
TI  - Promoting theory of mind during middle childhood: a training program.
AB  - Evidence that conversations about the mind foster improvements in theory of mind
      (ToM) is growing, but their efficacy in typically developing school-aged children
      has yet to be demonstrated. To address this gap, we designed a conversation-based
      training program for 9- and 10-year-olds and measured its effectiveness by pre-
      and post-test comparisons of performance on age-appropriate ToM tasks for two
      groups (matched at pre-test for gender, age, socioeconomic background, verbal
      ability, reading comprehension, executive functions, and ToM) who were assigned
      to either the intervention condition (n=45) or an active control condition
      (n=46). The intervention group showed significantly greater gains in ToM than the
      control group; this contrast was stable over 2 months, and (in a subsample) the
      improvement in ToM was independent of any changes in executive functions.
      Implications for the role of conversations about the mind in children's mental
      state reasoning are discussed.

PMID- 24892883
TI  - The development of intermodal emotion perception from bodies and voices.
AB  - Even in the absence of facial information, adults are able to efficiently extract
      emotions from bodies and voices. Although prior research indicates that 6.5-month
      old infants match emotional body movements to vocalizations, the developmental
      origins of this function are unknown. Moreover, it is not clear whether infants
      perceive emotion conveyed in static body postures and match them to
      vocalizations. In the current experiments, 6.5-month-olds matched happy and angry
      static body postures to corresponding vocalizations in upright images but not in
      inverted images. However, 3.5-month-olds failed to match. The younger infants
      also failed to match when tested with videos of emotional body movements that
      older infants had previously matched. Thus, whereas 6.5-month-olds process
      emotional cues from body images and match them to emotional vocalizations, 3.5
      month-olds do not exhibit such emotion knowledge. These results indicate
      developmental changes that lead to sophisticated emotion processing from bodies
      and voices early in life. 

PMID- 24892884
TI  - Preschoolers learn to switch with causally related feedback.
AB  - Training cognitive flexibility in preschoolers is of great interest but is not
      easy to achieve. In three experiments, we studied the effects of feedback on
      preschoolers' switch behavior with a computerized version of the Dimensional
      Change Card Sorting (DCCS) task. The task was designed such that feedback was
      connected to the stimulus and causally related to children's behavior.
      Experiments 1 and 2 showed that children receiving feedback on their post-switch
      behavior performed better than children administered a standard (no feedback)
      DCCS task. This effect transferred to a subsequent standard DCCS task after 5 min
      and after 1 week. Experiment 3 showed that children switched to the new post
      switch sorting rules and not to rules that oppose the pre-switch sorting rules.
      These results highlight preschoolers' sensitivity to the design of feedback in
      learning an abstract rule.

PMID- 24892885
TI  - Serotonin regulates contractile activity of the uterus in non-pregnant rabbits.
AB  - Serotonin (5-HT) can stimulate the cholinergic system of the uterus by indirect
      actions on the modulation of reflexes and a direct action on smooth muscles. We
      investigated the role of 5-HT in the regulation of the cholinergic activity in
      the uterine parts of non-pregnant rabbits. The right vagus or pelvic nerve and
      the left sympathetic trunk were stimulated by an electrical field, and the
      uterine contractile activity was evaluated by measuring the amplitude and
      frequency of slow wave electromyogram (EMG), with the surface of microelectrodes
      applied to the uterus bottom, body, and cervix, respectively. Double stimulation
      of the vagus or pelvic nerve and the sympathetic trunk increased the frequency
      and the amplitude of the slow wave EMG in all the uterine parts. Furthermore, the
      administration of exogenous 5-HT increased the vagus or pelvic induced EMG
      activity in all parts of the uterus. Overall our results demonstrate that 5-HT
      enhances the vagus contractile activity with a magnitude of the effect decreasing
      from the bottom to the cervix, whereas 5-HT enhances the pelvic nerve contractile
      functions with a magnitude of the response increasing from the bottom to the
      cervix. The administration of droperidol, a 5-HT3 and 4 receptor inhibitor, and
      spiperone, a 5-HT2 receptor antagonist, inhibited the effect of the
      serotoninergic fibers of the sympathetic trunk to increase the vagus and pelvic
      nerve EMG activity. These data suggest that 5-HT stimulation of the
      parasympathetic nerves results in the induction of uterine contraction via the
      activation of 5-HT2, 3, and 4 receptor subfamilies. 

PMID- 24892887
TI  - Increased striatal adenosine A2A receptor levels is an early event in Parkinson's
      disease-related pathology and it is potentially regulated by miR-34b.
AB  - Adenosine A2A receptor (A2AR) is a G-protein coupled receptor that stimulates
      adenylyl cyclase activity. In the brain, A2ARs are found highly enriched in
      striatal GABAergic medium spiny neurons, related to the control of voluntary
      movement. Pharmacological modulation of A2ARs is particularly useful in
      Parkinson's disease (PD) due to their property of antagonizing dopamine D2
      receptor activity. Increases in A2AR levels have been described in PD patients
      showing an important loss of dopaminergic denervation markers, but no data have
      been reported about A2AR levels in incidental PD brains. In the present report,
      we show that increased A2ARs protein levels were also detected in the putamen of
      incidental PD cases (Braak PD stages 1-2) with respect to age-matched controls.
      By contrast, A2ARs mRNA levels remained unchanged, suggesting that
      posttranslational mechanisms could be involved in the regulation of A2ARs. It has
      been described how miR-34b/c downregulation is an early event in PD cases. We
      found that miR-34b levels are also significantly reduced in the putamen of
      incidental PD cases and along disease progression. Given that 3'UTR of A2AR
      contains a predicted target site for miR-34b, the potential role of this miRNA in
      protein A2AR levels was assessed. In vitro studies revealed that endogenous A2AR
      protein levels increased when miR-34b function was blocked using a specific anti
      miR-34b. Moreover, using a luciferase reporter assay with point mutations in a
      miR-34b predicted binding site within the 3'UTR region of A2AR mRNA abolished the
      effect of the miRNA using a miR-34b mimic. In addition, we showed a reduced
      percentage of DNA methylation in the 5'UTR region of ADORA2A in advanced PD
      cases. Overall, these findings reveal that increased A2AR protein levels occur in
      asymptomatic PD patients and provide new insights into the molecular mechanisms
      underlying A2AR expression levels along the progression of this neurodegenerative
      disease. 

PMID- 24892886
TI  - RanBP9 overexpression accelerates loss of dendritic spines in a mouse model of
      Alzheimer's disease.
AB  - We previously demonstrated that RanBP9 overexpression increased Abeta generation
      and amyloid plaque burden, subsequently leading to robust reductions in the
      levels of several synaptic proteins as well as deficits in the learning and
      memory skills in a mouse model of Alzheimer's disease (AD). In the present study,
      we found striking reduction of spinophilin-immunoreactive puncta (52%, p<0.001)
      and spinophilin area (62.5%, p<0.001) in the primary cortical neurons derived
      from RanBP9 transgenic mice (RanBP9-Tg) compared to wild-type (WT) neurons.
      Similar results were confirmed in WT cortical neurons transfected with EGFP
      RanBP9. At 6-months of age, the total spine density in the cortex of RanBP9
      single transgenic, APDeltaE9 double transgenic and APDeltaE9/RanBP9 triple
      transgenic mice was similar to WT mice. However, in the hippocampus the spine
      density was significantly reduced (27%, p<0.05) in the triple transgenic mice
      compared to WT mice due to reduced number of thin spines (33%, p<0.05) and
      mushroom spines (22%, p<0.05). This suggests that RanBP9 overexpression in the
      APDeltaE9 mice accelerates loss of spines and that the hippocampus is more
      vulnerable. At 12-months of age, the cortex showed significant reductions in
      total spine density in the RanBP9 (22%, p<0.05), APDeltaE9 (19%, p<0.05) and
      APDeltaE9/RanBP9 (33%, p<0.01) mice compared to WT controls due to reductions in
      mushroom and thin spines. Similarly, in the hippocampus the total spine density
      was reduced in the RanBP9 (23%, p<0.05), APDeltaE9 (26%, p<0.05) and
      APDeltaE9/RanBP9 (39%, p<0.01) mice due to reductions in thin and mushroom
      spines. Most importantly, RanBP9 overexpression in the APDeltaE9 mice further
      exacerbated the reductions in spine density in both the cortex (14%, p<0.05) and
      the hippocampus (16%, p<0.05). Because dendritic spines are considered physical
      traces of memory, loss of spines due to RanBP9 provided the physical basis for
      the learning and memory deficits. Since RanBP9 protein levels are increased in AD
      brains, RanBP9 might play a crucial role in the loss of spines and synapses in
      AD. 

PMID- 24892889
TI  - Silencing of PmYPR65 receptor prevents yellow head virus infection in Penaeus
      monodon.
AB  - The suppression of viral replication by double-stranded RNAs (dsRNA) specific to
      mRNAs of either virus or host genes has been widely investigated as a possible
      shrimp disease therapy. PmYRP65, a yellow head virus (YHV) receptor, was
      previously identified and characterized in the black tiger shrimp, Penaeus
      monodon. In our previous study, entry of YHV into cells of the Oka organ of P.
      monodon required the host receptor PmYRP65 and silencing of PmYRP65 in vitro led
      to a complete suppression of YHV replication in the cells. In this study, PmYRP65
      was shown to be in vivo suppressed by dsRNA specific for PmYRP65, leading to
      inhibition of YHV replication and almost complete abolition of shrimp mortality
      following YHV challenge. Targeting PmYRP65 could be an effective YHV antiviral
      shrimp strategy. 

PMID- 24892890
TI  - The nexus of sleep psychology, psychiatry, and neurology in health.

PMID- 24892888
TI  - Using sex differences in the developing brain to identify nodes of influence for
      seizure susceptibility and epileptogenesis.
AB  - Sexual differentiation of the developing brain organizes the neural architecture
      differently between males and females, and the main influence on this process is
      exposure to gonadal steroids during sensitive periods of prenatal and early
      postnatal development. Many molecular and cellular processes are influenced by
      steroid hormones in the developing brain, including gene expression, cell birth
      and death, neurite outgrowth and synaptogenesis, and synaptic activity.
      Perturbations in these processes can alter neuronal excitability and circuit
      activity, leading to increased seizure susceptibility and the promotion of
      pathological processes that constitute epileptogenesis. In this review, we will
      provide a general overview of sex differences in the early developing brain that
      may be relevant for altered seizure susceptibility in early life, focusing on
      limbic areas of the brain. Sex differences that have the potential to alter the
      progress of epileptogenesis are evident at molecular and cellular levels in the
      developing brain, and include differences in neuronal excitability, response to
      environmental insult, and epigenetic control of gene expression. Knowing how
      these processes differ between the sexes can help us understand fundamental
      mechanisms underlying gender differences in seizure susceptibility and
      epileptogenesis.

PMID- 24892893
TI  - Sleep, obesity, and weight loss in adults: is there a rationale for providing
      sleep interventions in the treatment of obesity?
AB  - Rates of obesity and sleep disturbances are substantial in adults. A number of
      cross-sectional, longitudinal, and experimental studies have found that
      insufficient sleep and possibly longer sleep are associated with obesity and
      related eating patterns. Methodological discrepancies and limitations in the
      literature create ambiguity about the nature and potential mechanisms underlying
      these relationships. Insomnia and circadian patterns in eating and sleeping have
      also been examined in relation to weight. Although these studies are not as
      extensive as those examining sleep duration, the extant literature suggests
      possible associations between obesity and both insomnia (particularly when
      combined with short sleep duration) and circadian eating behaviours. However,
      research has only just begun to examine the benefits of combining sleep
      interventions with obesity treatment. The goal of the current review is to
      summarize research examining behavioural sleep patterns and disorders in relation
      to obesity, to discuss methodological considerations, and to provide an overview
      of studies examining whether addressing sleep disturbances can augment weight
      loss treatment effects. We conclude that future studies are needed that take into
      account sleep duration, sleep disorder co-morbidity, and chronobiology to explore
      the impact of sleep interventions on weight loss.

PMID- 24892894
TI  - Linkages between insomnia and suicidality: prospective associations, high-risk
      subgroups and possible psychological mechanisms.
AB  - Insomnia can be lethal, increasing the risk of suicide and accidental death by
      overdose. In this review we present a synthesis of the literature investigating
      the insomnia-suicide link and the psychological mechanisms underpinning the
      association. Specifically, we review the findings of prospective epidemiological
      studies demonstrating the insomnia-suicide link in adult and adolescent community
      populations. Robust associations between insomnia and suicide are observed in
      clinically depressed and anxious populations, and there are indications across a
      number of cross-sectional and longitudinal studies that these linkages are
      attributable to a disrupted sleep pattern, dysfunctional beliefs about sleep and
      nightmares, independent of depression and anxiety symptoms. Borderline
      personality disorder (BPD) and chronic pain (CP) are highlighted as high-risk
      subgroups given the elevated rates of insomnia and suicidality in both
      conditions. Aside from the influence of comorbid depression and anxiety symptoms,
      emerging evidence has identified impulsivity and emotional dysregulation as
      possible mechanisms driving the insomnia-suicide link in BPD, and catastrophizing
      and the sense of defeat/entrapment as potential cognitive pathways through which
      insomnia aggravates suicidality in CP. Screening for, and interventions that
      tackle, insomnia and these associated psychological mechanisms, offer a novel
      avenue for reducing suicidality across a range of clinical and non-clinical
      populations.

PMID- 24892895
TI  - Cognitive and behavioural therapy for insomnia (CBT-I) in psychiatric
      populations: a systematic review.
AB  - Insomnia is highly co-morbid with psychiatric disorders, making it a frequent
      issue in treatment planning in psychiatric clinics. Research has also shown that
      although insomnia may originally precede or be a consequence of a psychiatric
      disorder, insomnia likely becomes semi-independent, and may exacerbate those
      disorders if it is not addressed, leading to reduced treatment response.
      Cognitive behavioural therapy for insomnia (CBT-I) is now recommended as the
      first line of treatment of primary insomnia. The research reviewed below
      indicates that CBT-I in patients with co-morbid depression, anxiety, post
      traumatic stress disorder (PTSD), and substance abuse disorders is generally
      effective for insomnia and sometimes the co-morbid disorder as well. Although
      more research is needed before definitive recommendations can be made, it appears
      as though CBT-I is a viable approach to treating the patient with co-morbid
      insomnia and psychiatric disorders.

PMID- 24892896
TI  - New and emerging pharmacotherapeutic approaches for insomnia.
AB  - Advances in understanding the neurochemistry of sleep and waking have stimulated
      new pharmacological directions in the treatment of insomnia. While the sedation
      of historic insomnia medications was discovered serendipitously, now compounds
      can be developed for specific molecular targets with known sleep-related actions.
      Numerous investigational compounds, including some entirely novel approaches, are
      being evaluated currently as possible insomnia treatments. In recent years the US
      Federal Drug Administration (FDA) has approved medications with new
      pharmacodynamic and pharmacokinetic properties thereby extending the options for
      personalized pharmacotherapy. The FDA is reviewing new applications for
      innovative sleep-promoting medications currently, including suvorexant and
      tasimelteon. Presently the FDA-approved insomnia treatment medications include
      benzodiazepine receptor agonists available in immediate-release, extended
      release, and alternative delivery oral absorption formulations; a melatonin
      receptor agonist; and a histamine receptor antagonist. Clinical indications
      include insomnia associated with difficulty with sleep onset, sleep maintenance,
      and middle-of-the-night awakenings. Alternative approaches to treating insomnia
      have included prescription medications employed on an off-label basis for
      insomnia, over-the-counter sleep aids, and assorted unregulated substances
      marketed to enhance sleep.

PMID- 24892891
TI  - Circadian misalignment and health.
AB  - Circadian rhythms are near 24-h patterns of physiology and behaviour that are
      present independent of external cues including hormones, body temperature, mood,
      and sleep propensity. The term 'circadian misalignment' describes a variety of
      circumstances, such as inappropriately timed sleep and wake, misalignment of
      sleep/wake with feeding rhythms, or misaligned central and peripheral rhythms.
      The predominance of early research focused on misalignment of sleep to the
      biological night. However, discovery of clock genes and the presence of
      peripheral circadian oscillators have expanded the definitions of misalignment.
      Experimental studies conducted in animal models and humans have provided evidence
      of potential mechanisms that link misalignment to negative outcomes. These
      include dysregulation of feeding behaviours, changes in appetite stimulating
      hormones, glucose metabolism and mood. This review has two foci: (1) to describe
      how circadian misalignment has been defined and evaluated in laboratory and field
      experiments, and (2) to describe evidence linking different types of circadian
      misalignment to increased risk for physical (cardiovascular disease, diabetes,
      obesity, cancer) and psychiatric (depression, bipolar, schizophrenia, attention
      deficit) disorders. This review will describe the role of circadian misalignment
      as a risk factor for disease in the general population and in clinical
      populations, including circadian rhythm sleep disorders and psychiatric
      disorders.

PMID- 24892897
TI  - Pharmacological and non-pharmacological treatments for nightmare disorder.
AB  - Interest in the treatment of nightmares has greatly increased over the last
      several years as research has demonstrated the clinical significance of nightmare
      disorder. This paper provides an overview of nightmare disorder, its clinical
      relevance, and the leading treatments that are available. In particular, the
      paper defines nightmare disorder and then summarize the recent literature
      examining the clinical relevance of nightmare disorder, including its relation to
      post-traumatic stress disorder and other psychiatric conditions. The relation
      between nightmares and suicidality is also discussed. Recent findings on the
      treatment of nightmare with imagery rehearsal therapy and prazosin are then
      summarized. Lastly, the paper comments on potential future uses of nightmare
      treatment including using imagery rehearsal therapy or prazosin as a first-line
      intervention for post-traumatic stress disorder and using these treatments as an
      adjunctive therapy to reduce suicide risk in those at risk of suicide with
      nightmares.

PMID- 24892899
TI  - Restless legs syndrome/Willis Ekbom disease: evaluation and treatment.
AB  - Restless legs syndrome/Willis Ekbom disease (RLS/WED) has been recognized as a
      significant medical disorder since the 17th century. It was studied mostly in the
      last 50 years in relation to increasing interest in sleep medicine and health
      related quality of life. This led to recognition that the disease is not well
      characterized as restless feelings in the legs. These symptoms are reported in
      many situations, but the subjective experience of RLS/WED patients differs from
      that experienced by others. Thus a new name has been introduced that avoids
      problems of symptom definition of a disease by naming it after those who first
      characterized it, i.e. 'Willis Ekbom disease'. This article emphasizes the
      importance of RLS/WED for psychiatry. The disease carries significant increased
      risk for depression and anxiety disorders. Treatment requires consideration of
      these co-morbid disorders. RLS/WED can exacerbate or even engender psychiatric
      disease, so treatment of psychiatric disease should also include consideration of
      RLS/WED. The need for attention to RLS/WED is particularly significant for
      depression. Most anti-depressants exacerbate or can even engender RLS/WED. Thus
      this article seeks to introduce RLS/WED in relation to psychiatric practice. It
      presents the RLS/WED disease, its overlap with psychiatry and the current
      treatment options.

PMID- 24892900
TI  - The importance of membrane defects-lessons from simulations.
AB  - The defects and pores within lipid membranes are scientifically interesting and
      have a number of biological applications. Although lipid bilayers are extremely
      thin hydrophobic barriers, just ~3 nm thick, they include diverse chemistry and
      have complex structures. Bilayers are soft and dynamic, and as a result, they can
      bend and deform in response to different stimuli by means of structural changes
      in their component lipids. Though defects occur within these structures, their
      transience and small size have made it difficult to characterize them. However,
      with recent advances in computer power and computational modeling techniques,
      researchers can now use simulations as a powerful tool to probe the mechanism and
      energies of defect and pore formation in a number of situations. In this Account,
      we present results from our detailed molecular dynamics computer simulations of
      hydrophilic pores and related defects in lipid bilayers at an atomistic level.
      Electroporation can be used to increase the permeability of cellular membranes,
      with potential therapeutic applications. Atomistic simulations of electroporation
      have illustrated the molecular details of this process, including the importance
      of water dipole interactions at the water-membrane interface. Characterization of
      the lipid-protein interactions provides an important tool for understanding
      transmembrane protein structure and thermodynamic stability. Atomistic
      simulations give a detailed picture of the free energies of model peptides and
      side chains in lipid membranes; the energetic cost of defect formation strongly
      influences the energies of interactions between lipids and polar and charged
      residues. Many antimicrobial peptides form hydrophilic pores in lipid membranes,
      killing bacteria or cancer cells. On the basis of simulation data, at least some
      of these peptides form defects and pores near the center of the bilayer, with a
      common disordered structure where hydrated headgroups form an approximately
      toroidal shape. The localization and trafficking of lipids supports general
      membrane structure and a number of important signaling cascades, such as those
      involving ceramide, diacylglycerol, and cholesterol. Atomistic simulations have
      determined the rates and free energies of lipid flip-flop. During the flip-flop
      of most phosphatidylcholine lipids, a hydrophilic pore forms when the headgroup
      moves near the center of the bilayer. Simulations have provided novel insight
      into many features of defects and pores in lipid membranes. Simulation data from
      very different systems and models show how water penetration and defect formation
      can determine the free energies of many membrane processes. Bilayers can deform
      and allow transient defects and pores when exposed to a diverse range of stimuli.
      Future work will explore many aspects of membrane defects with increased
      resolution and scope, including the study of more complex lipid mixtures,
      membrane domains, and large-scale membrane remodeling. Such studies will examine
      processes including vesicle budding and fusion, non-bilayer lipid phases, and
      interactions between lipid bilayers and other biomolecules. Simulations provide
      information that complements experimental studies, allowing microscopic insight
      into experimental observations and suggesting novel hypotheses and experiments.
      These studies should enable a deeper understanding of the role of lipid bilayers
      in cellular biology and support the development of future lipid-based
      biotechnology.

PMID- 24892892
TI  - Addressing sleep disturbances: an opportunity to prevent cardiometabolic disease?
AB  - There is increasing awareness of the role of sleep disturbance as an important
      factor in health and disease. Although sub-clinical sleep disturbances
      (insufficient sleep duration or inadequate sleep quality) may be difficult to
      assess with conceptual and/or methodological clarity, this review attempts to
      summarize and synthesize these findings. First, the concept of sleep disturbance
      in a public health context is introduced, to provide context and rationale.
      Second, operational definitions of 'cardiometabolic disease' and 'sleep
      disturbance' are offered, to address many unclear operationalizations. Third, the
      extant literature is summarized regarding short or long sleep duration and/or
      insufficient sleep, insomnia and insomnia symptoms, general (non-specific sleep
      disturbances), circadian rhythm abnormalities that result in sleep disturbances,
      and, briefly, sleep-disordered breathing. Fourth, the review highlights the
      social/behavioural context of sleep, including discussions of sleep and
      race/ethnicity, socio-economic position, and other social/environmental factors,
      in order to place these findings in a social-environmental context relevant to
      public health. Fifth, the review highlights the issue of sleep as a domain of
      health behaviour and addresses issues regarding development of healthy sleep
      interventions. Finally, a research agenda of future directions is proposed.

PMID- 24892898
TI  - Interactions between disordered sleep, post-traumatic stress disorder, and
      substance use disorders.
AB  - Disordered sleep is associated with a number of adverse health consequences and
      is an integral component of many psychiatric disorders. Rates of substance use
      disorders (SUDs) are markedly higher among individuals with post-traumatic stress
      disorder (PTSD), and this relationship may be partly mediated by disturbed sleep.
      Sleep disturbances (e.g. insomnia, daytime sleepiness, vivid nightmares) are
      hallmark features of PTSD and there is evidence that individuals with PTSD engage
      in substance use as a means of coping with these symptoms. However, prolonged
      substance use can lead to more severe sleep disturbances due to the development
      of tolerance and withdrawal. Behavioural or pharmacological treatment of
      disordered sleep is associated with improved daytime symptoms and psychosocial
      functioning among individuals who have developed PTSD. Initial research also
      suggests that improving sleep could be similarly beneficial in reducing coping
      oriented substance use and preventing relapse among those seeking treatment for
      SUDs. Together, these findings suggest that ameliorating sleep disturbance among
      at-risk individuals would be a viable target for the prevention and treatment of
      PTSD and associated SUDs, but prospective research is needed to examine this
      hypothesis. Enhanced understanding of the interrelation between sleep, PTSD, and
      SUDs may yield novel prevention and intervention approaches for these costly,
      prevalent and frequently co-occurring disorders.

PMID- 24892901
TI  - Association between urine aldosterone and diastolic function in patients with
      primary aldosteronism and essential hypertension.
AB  - OBJECTIVE: To investigate the association between aldosterone and cardiac
      diastolic dysfunction. DESIGN AND METHODS: We prospectively enrolled 20 patients
      with primary aldosteronism (PA) and 22 patients with essential hypertension (EH).
      Plasma aldosterone concentration, plasma renin activity, and 24-h urine
      aldosterone level were measured. Echocardiography, including tissue Doppler image
      recordings, was performed. RESULTS: PA patients had a significantly higher left
      ventricular (LV) mass index and worse LV diastolic function than those in EH
      patients. Among various measures of aldosterone, log-transformed 24-h urine
      aldosterone level had the most consistent correlation with diastolic function.
      CONCLUSIONS: Aldosterone is strongly associated with LV diastolic dysfunction.
      Twenty-four hour urine aldosterone is a good indicator to evaluate the impact of
      aldosterone on LV diastolic function.

PMID- 24892902
TI  - Effect of the electric field frequency on ascorbic acid degradation during
      thermal treatment by ohmic heating.
AB  - In this work, the influence of the electric field frequency and solids content on
      the degradation kinetics of ascorbic acid during ohmic heating of acerola pulp
      and acerola serum was investigated. The degradation percentage of ascorbic acid
      in the pulp after 120 min of heating varied between 12 and 17%. For the serum,
      the degradation percentage was in the range of 13 and 18%. The results were
      fitted to the first-order model, and the kinetic rate constants ranged from 1.1
      to 1.6*10(-3) min(-1) and from 1.1 to 1.5*10(-3) min(-1) for pulp and serum,
      respectively. D values ranged between 1480 and 2145 min for the pulp and between
      1524 and 1951 min for the serum. A distinct behavior between the kinetic
      parameters of the pulp and serum in electric field frequencies ranging from 10 to
      1000 Hz indicates that the presence of distinct amounts and types of solids might
      affect the rate of the electron transfer in electrochemical reactions. These
      variables may also affect the polarization process stimulated by the oscillating
      electric field. The non-achievement of the equilibrium of the polarization
      process may have an influence on oxidation reactions, affecting the
      predisposition to hydrogen donation from the ascorbic acid molecule.

PMID- 24892903
TI  - Independent and combined associations of total sedentary time and television
      viewing time with food intake patterns of 9- to 11-year-old Canadian children.
AB  - The relationships among sedentary time, television viewing time, and dietary
      patterns in children are not fully understood. The aim of this paper was to
      determine which of self-reported television viewing time or objectively measured
      sedentary time is a better correlate of the frequency of consumption of healthy
      and unhealthy foods. A cross-sectional study was conducted of 9- to 11-year-old
      children (n = 523; 57.1% female) from Ottawa, Ontario, Canada. Accelerometers
      were used to determine total sedentary time, and questionnaires were used to
      determine the number of hours of television watching and the frequency of
      consumption of foods per week. Television viewing was negatively associated with
      the frequency of consumption of fruits, vegetables, and green vegetables, and
      positively associated with the frequency of consumption of sweets, soft drinks,
      diet soft drinks, pastries, potato chips, French fries, fruit juices, ice cream,
      fried foods, and fast food. Except for diet soft drinks and fruit juices, these
      associations were independent of covariates, including sedentary time. Total
      sedentary time was negatively associated with the frequency of consumption of
      sports drinks, independent of covariates, including television viewing. In
      combined sedentary time and television viewing analyses, children watching >2 h
      of television per day consumed several unhealthy food items more frequently than
      did children watching <=2 h of television, regardless of sedentary time. In
      conclusion, this paper provides evidence to suggest that television viewing time
      is more strongly associated with unhealthy dietary patterns than is total
      sedentary time. Future research should focus on reducing television viewing time,
      as a means of improving dietary patterns and potentially reducing childhood
      obesity. 

PMID- 24892906
TI  - Expertise.
AB  - Ericsson discusses the history of research on the superior performance of experts
      in diverse fields from sport to music, including new insights that could be used
      to increase performance in the general population. 

PMID- 24892907
TI  - Selective attention in birds.
AB  - The natural world constantly inundates our senses with an abundance of
      information. Selective attention enables us to navigate this abundance
      intelligently by selecting the information that is most relevant, at each moment
      in time, for differential processing and decision-making. The attributes of
      attention have been studied in humans for over a century. In his influential
      19(th) century treatise, The Principles of Psychology, philosopher and
      psychologist William James defined attention as: "... the taking possession by
      the mind, in clear and vivid form, of one out of what seem several simultaneously
      possible objects or trains of thought ... It implies withdrawal from some things
      in order to deal effectively with others." (James, 1890). James' definition
      elegantly captures two key hallmarks of attention: the enhanced processing of
      task-relevant information (target information) and the suppression of task
      irrelevant information (distracting information). 

PMID- 24892904
TI  - Neuroanatomical abnormalities in chronic tinnitus in the human brain.
AB  - In this paper, we review studies that have investigated brain morphology in
      chronic tinnitus in order to better understand the underlying pathophysiology of
      the disorder. Current consensus is that tinnitus is a disorder involving a
      distributed network of peripheral and central pathways in the nervous system.
      However, the precise mechanism remains elusive and it is unclear which structures
      are involved. Given that brain structure and function are highly related,
      identification of anatomical differences may shed light upon the mechanism of
      tinnitus generation and maintenance. We discuss anatomical changes in the
      auditory cortex, the limbic system, and prefrontal cortex, among others.
      Specifically, we discuss the gating mechanism of tinnitus and evaluate the
      evidence in support of the model from studies of brain anatomy. Although
      individual studies claim significant effects related to tinnitus, outcomes are
      divergent and even contradictory across studies. Moreover, results are often
      confounded by the presence of hearing loss. We conclude that, at present, the
      overall evidence for structural abnormalities specifically related to tinnitus is
      poor. As this area of research is expanding, we identify some key considerations
      for research design and propose strategies for future research. 

PMID- 24892905
TI  - CMZ reversed chronic ethanol-induced disturbance of PPAR-alpha possibly by
      suppressing oxidative stress and PGC-1alpha acetylation, and activating the MAPK
      and GSK3beta pathway.
AB  - BACKGROUND: Cytochrome P4502E1 (CYP2E1) has been suggested to play critical roles
      in the pathogenesis of alcoholic fatty liver (AFL), but the underlying mechanisms
      remains unclear. The current study was designed to evaluate whether CYP2E1
      suppression by chlormethiazole (CMZ) could suppress AFL in mice, and to explore
      the underlying mechanisms. METHODS: Mice were treated with or without CMZ (50
      mg/kg bw, i.p.) and subjected to liquid diet with or without ethanol (5%, w/v)
      for 4 weeks. Biochemical parameters were measured using commercial kits. The
      protein and mRNA levels were detected by western blot and qPCR, respectively.
      Histopathology and immunohistochemical assay were performed with routine methods.
      RESULTS: CYP2E1 inhibition by CMZ completely blocked AFL in mice, shown as the
      decline of the hepatic and serum triglyceride levels, and the fewer fat droplets
      in the liver sections. Chronic ethanol exposure led to significant decrease of
      the mRNA and protein levels of peroxisome proliferator-activated receptor alpha
      (PPAR-alpha), which was blocked by CMZ co-treatment. CMZ co-treatment suppressed
      ethanol-induced oxidative stress, overproduction of tumor necrosis alpha (TNF
      alpha), and decrease of protein levels of the PPAR-alpha co-activators including
      p300 and deacetylated PGC1-alpha. Furthermore, CMZ co-treatment led to the
      activation of AMP-activated protein kinase (AMPK), mitogen-activated protein
      kinase (MAPK), and PI3K/Akt/GSK3beta pathway. However, chronic ethanol-induced
      decline of acyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) protein
      levels was partially restored by CMZ, while the activation of autophagy appeared
      to be suppressed by CMZ. CONCLUSION: These results suggested that CMZ suppressed
      chronic ethanol-induced oxidative stress, TNF-alpha overproduction, decline of
      p300 protein level and deacetylation of PGC1-alpha, and activated AMPK, MAPK, and
      PI3K/Akt/GSK3beta pathway, which might contribute to the activation of PPAR-alpha
      and account for the protection of CMZ against AFL.

PMID- 24892908
TI  - Seabird movement reveals the ecological footprint of fishing vessels.
AB  - Exploitation of the seas is currently unsustainable, with increasing demand for
      marine resources placing intense pressure on the Earth's largest ecosystem [1].
      The scale of anthropogenic effects varies from local to entire ocean basins [1
      3]. For example, discards of commercial capture fisheries can have both positive
      and negative impacts on scavengers at the population and community-level [2-6],
      although this is driven by individual foraging behaviour [3,7]. Currently, we
      have little understanding of the scale at which individual animals initiate such
      behaviours. We use the known interaction between fisheries and a wide-ranging
      seabird, the Northern gannet Morus bassanus[3], to investigate how fishing
      vessels affect individual birds' behaviours in near real-time. We document the
      footprint of fishing vessels' (>=15 m length) influence on foraging decisions
      (<=11 km), and a potential underlying behavioural mechanism, by revealing how
      birds respond differently to vessels depending on gear type and activity. Such
      influences have important implications for fisheries, including the proposed
      discard ban [8]), and wider marine management. 

PMID- 24892909
TI  - Publication metrics and success on the academic job market.
AB  - The number of applicants vastly outnumbers the available academic faculty
      positions. What makes a successful academic job market candidate is the subject
      of much current discussion [1-4]. Yet, so far there has been no quantitative
      analysis of who becomes a principal investigator (PI). We here use a machine
      learning approach to predict who becomes a PI, based on data from over 25,000
      scientists in PubMed. We show that success in academia is predictable. It depends
      on the number of publications, the impact factor (IF) of the journals in which
      those papers are published, and the number of papers that receive more citations
      than average for the journal in which they were published (citations/IF).
      However, both the scientist's gender and the rank of their university are also of
      importance, suggesting that non-publication features play a statistically
      significant role in the academic hiring process. Our model (www.pipredictor.com)
      allows anyone to calculate their likelihood of becoming a PI.

PMID- 24892910
TI  - Organelle evolution: a mosaic of 'mitochondrial' functions.
AB  - An ancient endosymbiosis of an alpha-proteobacterium produced a diverse range of
      organelles including mitochondria. Reconstruction of the Pygsuia biforma proteome
      adds to the mosaic of functional systems present in mitochondrial-related
      organelles and demonstrates the role of horizontal gene transfer.

PMID- 24892911
TI  - Neuroethology: self-recognition helps octopuses avoid entanglement.
AB  - How an octopus performs complex movements of its eight sucker-studded arms
      without entanglement has been a mystery. A new study has found that self
      recognition of the octopus's skin by its suckers inhibits reflexive grasping of
      its own arms, simplifying the mechanisms needed to generate intricate arm
      behavior. 

PMID- 24892912
TI  - Bacterial evolution: rewiring modules to get in shape.
AB  - Bacterial species take on a wide variety of shapes, but the mechanisms by which
      specific shapes evolve have remained poorly understood. A recent study
      demonstrates that two Asticcacaulis species repurposed an ancestral regulatory
      protein to rewire the modules of stalk regulation, localization, and synthesis,
      thereby generating new shapes.

PMID- 24892913
TI  - Ecology: honey bee foraging in human-modified landscapes.
AB  - Comprehensive information on the spatial resource use of honey bees is rare, but
      highly relevant to assess the consequences of habitat loss and fragmentation,
      agricultural intensification or extensification on colony fitness, pesticide
      exposure risks and pollination functions. 

PMID- 24892914
TI  - Cytoskeleton: cirque du septins.
AB  - Septins and F-actin are familiar cohabitants of the cleavage furrow yet how they
      might be functionally connected has been ambiguous. New work shows that septins
      can promote the assembly of curved bundles of F-actin, providing an unexpected
      molecular function for septins in cytokinesis. 

PMID- 24892915
TI  - Insect neurobiology: how small brains perform complex tasks.
AB  - A new study finds that bumblebees, like primates, can perform simple tasks that
      rely on rapid visual assessment, but unlike primates, require longer views for
      complex tasks. This suggests a fundamental difference in the way bees process
      visual information. 

PMID- 24892916
TI  - Cell division: the prehistorichore?
AB  - The recent discovery of a novel kinetochore has important implications for our
      understanding of the evolution of chromosome segregation systems and also for the
      treatment of devastating parasitic diseases. 

PMID- 24892917
TI  - Crossmodal integration: a glimpse into the development of sensory remapping.
AB  - Correctly localising sensory stimuli in space is a formidable challenge for the
      newborn brain. A new study provides a first glimpse into how human brain
      mechanisms for sensory remapping develop in the first year of life. 

PMID- 24892918
TI  - Checks and balances between cohesin and polycomb in gene silencing and
      transcription.
AB  - The cohesin protein complex was discovered for its roles in sister chromatid
      cohesion and segregation, and the Polycomb group (PcG) proteins for their roles
      in epigenetic gene silencing during development. Cohesin also controls gene
      transcription via multiple mechanisms. Genetic and molecular evidence from
      Drosophila argue that cohesin and the PRC1 PcG complex interact to control
      transcription of many active genes that are critical for development, and that
      via these interactions cohesin also controls the availability of PRC1 for gene
      silencing.

PMID- 24892920
TI  - Safety and efficacy of retrograde intrarenal surgery for renal stones in patients
      with a solitary kidney: a single-center experience.
AB  - BACKGROUND AND PURPOSE: The management of urolithiasis in patients with a
      solitary kidney is challenging for endourologists. This study was aimed at
      evaluating the safety and efficacy of retrograde intrarenal surgery (RIRS) in the
      treatment of such patients with renal stones. PATIENTS AND METHODS: Between
      January 2010 and January 2014, we enrolled 45 patients who had a solitary kidney
      and underwent RIRS and holmium:yttrium-aluminum-garnet lithotripsy for the
      management of renal stones. We collected data pertaining to the preoperative
      patient characteristics, stone dimensions, and postoperative outcomes. RESULTS:
      Sixty-eight procedures were performed in all. The mean stone diameter was 1.84+/
      0.19 cm (range 0.5-6.0 cm), and the mean operative time, 76.4+/-40.14 minutes
      (range 18-190 min). The percentages of patients free of renal stones at the
      initial and final procedures were 64.44% and 93.33%, respectively. The mean
      number of procedures needed for the patients with renal stones of diameters >=20
      mm and <20 mm were 1.93 per patient and 1.23 per patient, respectively (P=0.009).
      Postoperative complications (graded by the Clavien system) were noted in 26.6% of
      the patients (12/45): Grade I complications, in 20% (9/45); grade II
      complications, in 4.4% (2/45); and grade III complication, in 2.2% (1/45). The
      grade III complication was anuria because of Steinstrasse, which necessitated
      emergency surgery. CONCLUSIONS: RIRS for the removal of renal stones in patients
      with a solitary kidney affords a high success rate and low morbidity rate. For
      patients with large stones, however, a multistaged approach may be needed.

PMID- 24892923
TI  - Capturing carbon dioxide as a polymer from natural gas.
AB  - Natural gas is considered the cleanest and recently the most abundant fossil fuel
      source, yet when it is extracted from wells, it often contains 10-20 mol% carbon
      dioxide (20-40 wt%), which is generally vented to the atmosphere. Efforts are
      underway to contain this carbon dioxide at the well-head using inexpensive and
      non-corrosive methods. Here we report nucleophilic porous carbons are synthesized
      from simple and inexpensive carbon-sulphur and carbon-nitrogen precursors.
      Infrared, Raman and (13)C nuclear magnetic resonance signatures substantiate
      carbon dioxide fixation by polymerization in the carbon channels to form
      poly(CO2) under much lower pressures than previously required. This growing
      chemisorbed sulphur- or nitrogen-atom-initiated poly(CO2) chain further displaces
      physisorbed hydrocarbon, providing a continuous carbon dioxide selectivity. Once
      returned to ambient conditions, the poly(CO2) spontaneously depolymerizes,
      leading to a sorbent that can be easily regenerated without the thermal energy
      input that is required for traditional sorbents.

PMID- 24892924
TI  - Reducing protein adsorption with polymer-grafted hyaluronic acid coatings.
AB  - We report a thermoresponsive chemical modification strategy of hyaluronic acid
      (HA) for coating onto a broad range of biomaterials without relying on chemical
      functionalization of the surface. Poly(di(ethylene glycol) methyl ether
      methacrylate) (PMEO2MA), a polymer with a lower critical solution temperature of
      26  degrees C in water, was grafted onto HA to allow facile formation of
      biopolymer coatings. While the mechanism for film formation appears to involve a
      complex combination of homogeneous nucleation followed by heterogeneous film
      growth, we demonstrate that it resulted in hydrophilic coatings that
      significantly reduce protein adsorption despite the high fraction of hydrophobic
      (PMEO2MA). Structural characterization was performed using atomic force
      microscopy (AFM), which showed the formation of a dense, continuous coating based
      on 200 nm domains that were stable in protein solutions for at least 15 days. The
      coatings had a water contact angle of 16 degrees , suggesting the formation of
      hydrophilic but not fully wetting films. Quartz crystal microbalance with
      dissipation monitoring (QCM-D) as well as biolayer interferometry (BLI)
      techniques were used to measure adsorption of bovine serum albumin (BSA),
      fibrinogen (Fbg), and human immunoglobulin (IgG), with results indicating that HA
      PMEO2MA-coated surfaces effectively inhibited adsorption of all three serum
      proteins. These results are consistent with previous studies demonstrating that
      this degree of hydrophilicity is sufficient to generate an effectively nonfouling
      surface and suggest that segregation during the solubility transition resulted in
      a surface that presented the hydrophilic HA component of the hybrid biopolymer.
      We conclude that PMEO2MA-grafted HA is a versatile platform for the passivation
      of hydrophobic biomaterial surfaces without need for substrate functionalization.

PMID- 24892925
TI  - Postural control is not systematically related to reading skills: implications
      for the assessment of balance as a risk factor for developmental dyslexia.
AB  - Impaired postural control has been associated with poor reading skills, as well
      as with lower performance on measures of attention and motor control variables
      that frequently co-occur with reading difficulties. Measures of balance and motor
      control have been incorporated into several screening batteries for developmental
      dyslexia, but it is unclear whether the relationship between such skills and
      reading manifests as a behavioural continuum across the range of abilities or is
      restricted to groups of individuals with specific disorder phenotypes. Here were
      obtained measures of postural control alongside measures of reading, attention
      and general cognitive skills in a large sample of young adults (n = 100).
      Postural control was assessed using centre of pressure (CoP) measurements,
      obtained over 5 different task conditions. Our results indicate an absence of
      strong statistical relationships between balance measures with either reading,
      cognitive or attention measures across the sample as a whole.

PMID- 24892919
TI  - Gender differences in ocular blood flow.
AB  - Gender medicine has been a major focus of research in recent years. The present
      review focuses on gender differences in the epidemiology of the most frequent
      ocular diseases that have been found to be associated with impaired ocular blood
      flow, such as age-related macular degeneration, glaucoma and diabetic
      retinopathy. Data have accumulated indicating that hormones have an important
      role in these diseases, since there are major differences in the prevalence and
      incidence between men and pre- and post-menopausal women. Whether this is related
      to vascular factors is, however, not entirely clear. Interestingly, the current
      knowledge about differences in ocular vascular parameters between men and women
      is sparse. Although little data is available, estrogen, progesterone and
      testosterone are most likely important regulators of blood flow in the retina and
      choroid, because they are key regulators of vascular tone in other organs.
      Estrogen seems to play a protective role since it decreases vascular resistance
      in large ocular vessels. Some studies indicate that hormone therapy is beneficial
      for ocular vascular disease in post-menopausal women. This evidence is, however,
      not sufficient to give any recommendation. Generally, remarkably few data are
      available on the role of sex hormones on ocular blood flow regulation, a topic
      that requires more attention in the future.

PMID- 24892926
TI  - Genetic resistance to flaviviruses.

PMID- 24892927
TI  - Higher HIV DNA in CD4+ naive T-cells during acute HIV-1 infection in rapid
      progressors.
AB  - AbFew reports have shown the relationship between the distribution of human
      immunodeficiency virus type 1 (HIV-1) proviral DNA in CD4 subsets during acute
      HIV-1 infection and HIV disease progression. In this study, we enrolled two
      groups with distinct differences in disease progression. The CD4 counts of one
      group fell below 200 cells/MUL within 2 years (rapid progressors), whereas the
      other group maintained CD4 counts above 500 cells/MUL (slow progressors). We
      collected blood samples during Fiebig stage III-IV of the two groups, and sorted
      CD4+ naive, central memory, and effector memory lymphocytes. Real-time polymerase
      chain reaction was used to quantify HIV-1 DNA of the subsets. We found that HIV-1
      DNA content was higher in memory T-cells than in naive cells in both groups, and
      a higher HIV DNA content was found in naive CD4+ T-cells during acute HIV-1
      infection in rapid progressors. This suggests that higher HIV DNA in naive CD4+ T
      cells may associated with rapid progression.

PMID- 24892928
TI  - A systematic review of the Robson classification for caesarean section: what
      works, doesn't work and how to improve it.
AB  - BACKGROUND: Caesarean sections (CS) rates continue to increase worldwide without
      a clear understanding of the main drivers and consequences. The lack of a
      standardized internationally-accepted classification system to monitor and
      compare CS rates is one of the barriers to a better understanding of this trend.
      The Robson's 10-group classification is based on simple obstetrical parameters
      (parity, previous CS, gestational age, onset of labour, fetal presentation and
      number of fetuses) and does not involve the indication for CS. This
      classification has become very popular over the last years in many countries. We
      conducted a systematic review to synthesize the experience of users on the
      implementation of this classification and proposed adaptations. METHODS: Four
      electronic databases were searched. A three-step thematic synthesis approach and
      a qualitative metasummary method were used. RESULTS: 232 unique reports were
      identified, 97 were selected for full-text evaluation and 73 were included. These
      publications reported on the use of Robson's classification in over 33 million
      women from 31 countries. According to users, the main strengths of the
      classification are its simplicity, robustness, reliability and flexibility.
      However, missing data, misclassification of women and lack of definition or
      consensus on core variables of the classification are challenges. To improve the
      classification for local use and to decrease heterogeneity within groups, several
      subdivisions in each of the 10 groups have been proposed. Group 5 (women with
      previous CS) received the largest number of suggestions. CONCLUSIONS: The use of
      the Robson classification is increasing rapidly and spontaneously worldwide.
      Despite some limitations, this classification is easy to implement and interpret.
      Several suggested modifications could be useful to help facilities and countries
      as they work towards its implementation.

PMID- 24892930
TI  - Interaction of obesity and central obesity on elevated urinary albumin-to
      creatinine ratio.
AB  - BACKGROUND: Microalbuminuria was much more common among obese individuals
      indicating a probable association with obesity. However, association of
      microalbuminuria with interaction between obesity and central obesity has not yet
      been studied. DESIGN AND METHODS: A cross-sectional study was conducted in a 2889
      general population aged >= 30 years. Obesity was defined as body mass index >=
      28.0 kg/m2 and central obesity was defined as waist-to-hip ratio >= 0.85 for
      females and >= 0.90 for males. Both additive and multipliable interactions
      between obesity and central obesity on elevated urinary albumin-to-creatinine
      ratio (UACR) were evaluated. RESULTS: After controlling for potential covariates,
      participants with both obesity and central obesity have significantly increased
      risk for elevated UACR (OR = 1.82 P<0.001) compared to those with neither.
      Additive interaction analysis indicated that about 43.9% of the risk of elevated
      UACR in participants with both obesity and central obesity was attributed to the
      interaction between obesity and central obesity (the attributable proportion
      because of the interaction: 0.439; 95% CI: 0.110-0.768). The multipliable
      interactive effect between obesity and central obesity on elevated UACR was not
      found significant (OR = 1.82, P = 0.078). CONCLUSIONS: Microalbuminuria was
      significantly associated with the interaction between obesity and central
      obesity. Our results indicated that individuals with both obesity and central
      obesity should be intensively managed to prevent renal diseases.

PMID- 24892931
TI  - Methane, carbon dioxide and nitrous oxide fluxes in soil profile under a winter
      wheat-summer maize rotation in the North China Plain.
AB  - The production and consumption of the greenhouse gases (GHGs) methane (CH4),
      carbon dioxide (CO2) and nitrous oxide (N2O) in soil profile are poorly
      understood. This work sought to quantify the GHG production and consumption at
      seven depths (0-30, 30-60, 60-90, 90-150, 150-200, 200-250 and 250-300 cm) in a
      long-term field experiment with a winter wheat-summer maize rotation system, and
      four N application rates (0; 200; 400 and 600 kg N ha(-1) year(-1)) in the North
      China Plain. The gas samples were taken twice a week and analyzed by gas
      chromatography. GHG production and consumption in soil layers were inferred using
      Fick's law. Results showed nitrogen application significantly increased N2O
      fluxes in soil down to 90 cm but did not affect CH4 and CO2 fluxes. Soil moisture
      played an important role in soil profile GHG fluxes; both CH4 consumption and CO2
      fluxes in and from soil tended to decrease with increasing soil water filled pore
      space (WFPS). The top 0-60 cm of soil was a sink of atmospheric CH4, and a source
      of both CO2 and N2O, more than 90% of the annual cumulative GHG fluxes originated
      at depths shallower than 90 cm; the subsoil (>90 cm) was not a major source or
      sink of GHG, rather it acted as a 'reservoir'. This study provides quantitative
      evidence for the production and consumption of CH4, CO2 and N2O in the soil
      profile.

PMID- 24892933
TI  - Breast density assessment using a 3T MRI system: comparison among different
      sequences.
AB  - PURPOSE: To compare MRI sequences for breast density measurements on a 3T MRI
      system using IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry
      and Least squares estimation) as possible physiology-like reference. MATERIALS
      AND METHODS: MRI examination was performed in 48 consecutive patients (mean age
      41, years; range, 35-67 years) on a 3.0T scanner and 46 were included. All
      (fertile) women, were examined between days 5 and 15 of their menstrual cycle.
      MRI protocol included: T1-turbo spin-echo (T1-tSE), T2-turbo spin-echo (T2-tSE),
      VIBRANT (Volume Imaging for Breast Assessment) before and after injection of
      contrast media and IDEAL. Breast density was calculated with semi-automated
      software. Statistical analysis was performed with non-parametric tests. RESULTS:
      Mean percentage of breast density calculated in each sequence was: T1-tSE = 56%;
      T2-tSE  = 52%; IDEAL FatOnly  = 55%; IDEAL WaterOnly  = 53%, VIBRANT = 55%.
      Significant differences were observed between T2-tSE and both T1-tSE (p<0.001),
      VIBRANT sequences (p = 0.009), T1-tSE and both IDEAL WaterOnly (p = 0.007) and
      IDEAL FatOnly (p = 0.047). Breast density percentage showed a positive linear
      correlation among different sequences: r >= 0.93. CONCLUSIONS: Differences exist
      between MRI sequences used to assess breast density percentage. T1-weighted
      sequences values were similar to IDEAL sequences.

PMID- 24892935
TI  - AST: an automated sequence-sampling method for improving the taxonomic diversity
      of gene phylogenetic trees.
AB  - A challenge in phylogenetic inference of gene trees is how to properly sample a
      large pool of homologous sequences to derive a good representative subset of
      sequences. Such a need arises in various applications, e.g. when (1) accuracy
      oriented phylogenetic reconstruction methods may not be able to deal with a large
      pool of sequences due to their high demand in computing resources; (2)
      applications analyzing a collection of gene trees may prefer to use trees with
      fewer operational taxonomic units (OTUs), for instance for the detection of
      horizontal gene transfer events by identifying phylogenetic conflicts; and (3)
      the pool of available sequences is biased towards extensively studied species. In
      the past, the creation of subsamples often relied on manual selection. Here we
      present an Automated sequence-Sampling method for improving the Taxonomic
      diversity of gene phylogenetic trees, AST, to obtain representative sequences
      that maximize the taxonomic diversity of the sampled sequences. To demonstrate
      the effectiveness of AST, we have tested it to solve four problems, namely,
      inference of the evolutionary histories of the small ribosomal subunit protein S5
      of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a
      study of ancient horizontal gene transfers from bacteria to plants. Our results
      show that the resolution of our computational results is almost as good as that
      of manual inference by domain experts, hence making the tool generally useful to
      phylogenetic studies by non-phylogeny specialists. The program is available at
      http://csbl.bmb.uga.edu/~zhouchan/AST.php. 

PMID- 24892934
TI  - Gene pleiotropy constrains gene expression changes in fish adapted to different
      thermal conditions.
AB  - Understanding the factors that shape the evolution of gene expression is a
      central goal in biology, but the molecular mechanisms behind this remain
      controversial. A related major goal is ascertaining how such factors may affect
      the adaptive potential of a species or population. Here we demonstrate that
      temperature-driven gene expression changes in fish adapted to differing thermal
      environments are constrained by the level of gene pleiotropy estimated by either
      the number of protein interactions or gene biological processes. Genes with low
      pleiotropy levels were the main drivers of both plastic and evolutionary global
      expression profile changes, while highly pleiotropic genes had limited expression
      response to temperature treatment. Our study provides critical insights into the
      molecular mechanisms by which natural populations can adapt to changing
      environments. In addition to having important implications for climate change
      adaptation, these results suggest that gene pleiotropy should be considered more
      carefully when interpreting expression profiling data. 

PMID- 24892938
TI  - A tetrahedron-based endmember selection approach for urban impervious surface
      mapping.
AB  - The pixel purity index (PPI) and two-dimensional (2-D) scatter plots are two
      popular techniques for endmember extraction in remote sensing spectral mixture
      analysis, yet both suffer from one major drawback, that is, the selection of a
      final set of endmembers has to endure a cumbersome process of iterative visual
      inspection and human intervention, especially when a spectrally-complex urban
      scene is involved. Within the conceptual framework of a V-H-L-S (vegetation-high
      albedo-low albedo-soil) model, which is expanded from the classic V-I-S
      (vegetation-impervious surface-soil) model, a tetrahedron-based endmember
      selection approach combined with a multi-objective optimization genetic algorithm
      (MOGA) was designed to identify urban endmembers from multispectral imagery. The
      tetrahedron defining the enclosing volume of MNF-transformed pixels in a three
      dimensional (3-D) space was algorithmically sought, so that the tetrahedral
      vertices can ideally match the four components of the adopted model. A case study
      with Landsat Enhanced Thematic Mapper Plus (ETM+) satellite imagery in Shanghai,
      China was conducted to verify the validity of the method. The method performance
      was compared with those of the traditional PPI and 2-D scatter plots approaches.
      The results indicated that the tetrahedron-based endmember selection approach
      performed better in both accuracy and ease of identification for urban surface
      endmembers owing to the 3-D visualization analysis and use of the MOGA. 

PMID- 24892937
TI  - Pneumococcal serotypes and serogroups causing invasive disease in Pakistan, 2005
      2013.
AB  - While pneumococcal conjugate vaccines have been implemented in most countries
      worldwide, use in Asia has lagged in part because of a lack of data on the amount
      of disease that is vaccine preventable in the region. We describe pneumococcal
      serotypes elicited from 111 episodes of invasive pneumococcal disease (IPD) from
      2005 to 2013 among children and adults in Pakistan. Seventy-three percent (n =
      81) of 111 IPD episodes were cases of meningitis (n = 76 in children 0-15 years
      and n = 5 among adults). Serotypes were determined by target amplification of DNA
      extracted from pneumococcal isolates (n = 52) or CSF specimens (n = 59).
      Serogroup 18 was the most common serogroup causing meningitis in children <5
      years, accounting for 21% of cases (n = 13). The 10-valent pneumococcal conjugate
      vaccine (PCV 10) or PCV10- related serotypes were found in 61% (n = 47) of
      childhood (age 0-15 years) meningitis episodes. PCV-13 increased this coverage to
      63% (one additional serotype 19A; n = 48). Our data indicate that use of PCVs
      would prevent a large proportion of serious pneumococcal disease.

PMID- 24892936
TI  - Subtypes of patients experiencing exacerbations of COPD and associations with
      outcomes.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous
      condition characterized by occasional exacerbations. Identifying clinical
      subtypes among patients experiencing COPD exacerbations (ECOPD) could help better
      understand the pathophysiologic mechanisms involved in exacerbations, establish
      different strategies of treatment, and improve the process of care and patient
      prognosis. The objective of this study was to identify subtypes of ECOPD patients
      attending emergency departments using clinical variables and to validate the
      results using several outcomes. We evaluated data collected as part of the IRYSS
      COPD prospective cohort study conducted in 16 hospitals in Spain. Variables
      collected from ECOPD patients attending one of the emergency departments included
      arterial blood gases, presence of comorbidities, previous COPD treatment,
      baseline severity of COPD, and previous hospitalizations for ECOPD. Patient
      subtypes were identified by combining results from multiple correspondence
      analysis and cluster analysis. Results were validated using key outcomes of ECOPD
      evolution. Four ECOPD subtypes were identified based on the severity of the
      current exacerbation and general health status (largely a function of
      comorbidities): subtype A (n = 934), neither high comorbidity nor severe
      exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562),
      severe comorbidities related to mortality; and subtype D (n = 309), very severe
      process of exacerbation, significantly related to mortality and admission to an
      intensive care unit. Subtype D experienced the highest rate of mortality,
      admission to an intensive care unit and need for noninvasive mechanical
      ventilation, followed by subtype C. Subtypes A and B were primarily related to
      other serious complications. Hospitalization rate was more than 50% for all the
      subtypes, although significantly higher for subtypes C and D than for subtypes A
      and B. These results could help identify characteristics to categorize ECOPD
      patients for more appropriate care, and help test interventions and treatments in
      subgroups with poor evolution and outcomes.

PMID- 24892939
TI  - Sequential therapy in chronic myelogenous leukemia: where do emerging therapies
      fit within current treatment regimens?
AB  - Chronic myelogenous leukemia (CML) is a slowly progressing malignancy that most
      often includes a clonal genetic aberration (the Philadelphia chromosome) that
      results in the BCR-ABL fusion protein, a constitutively activated tyrosine
      kinase. The management of CML was revolutionized more than a decade ago with the
      introduction of imatinib, a targeted inhibitor of the BCR-ABL protein. Imatinib
      has improved outcome and increased survival, but a substantial number of patients
      will develop resistance or intolerance to therapy. The second-generation tyrosine
      kinase inhibitors nilotinib and dasatinib are now approved in both the first-line
      and second-line settings. More recently, ponatinib and bosutinib were approved
      for resistant or refractory disease. This expansion to the treatment
      armamentarium has raised questions regarding the best selection and sequencing of
      agents. Clinical trials are now beginning to address these issues and others. The
      many treatment options in CML can offer patients improved outcomes, greater
      quality of life, and increased survival.

PMID- 24892944
TI  - Modulation of renin angiotensin system predominantly alters sclerotic phenotype
      of glomeruli in HIVAN.
AB  - HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in
      patients with African ancestry in general and with APOL1 gene risk variants in
      particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN,
      significant numbers of glomeruli in patients with HIVAN also display other
      variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed
      glomeruli as well as glomeruli with other variants of FSGS are manifestations of
      HIVAN and their prevalence depends on associated host factors. We explored the
      role of the renin-angiotensin system (RAS) in the manifestation of any specific
      glomerular phenotype in HIVAN. To evaluate the role of the RAS we have used a
      genetically engineered mouse model of HIVAN (Tg26) with two and four copies of
      angiotensinogen (Agt) gene (Tg26/Agt2 and Tg26/Agt4). In Tg26/Agt2, 1 out of 6
      glomeruli exhibited sclerosed phenotype, whereas 1 out of 25 glomeruli displayed
      collapsed phenotype; on the other hand, in Tg26/Agt4, 1 out of 3 glomeruli
      exhibited sclerotic phenotype and only 1 out of 7 glomeruli showed collapsed
      phenotype. To inhibit the effect of RAS, Tg26/Agt2 were administered captopril,
      aliskiren, aliskiren plus captopril or aliskiren plus telmisartan by miniosmotic
      pumps for 4 weeks. In all experimental groups there was a significant reduction
      in percentage of sclerosed glomeruli and only minimal reduction in collapsed
      glomeruli compared to normal saline receiving Tg26/Agt2. These findings suggest
      that the manifestation of the sclerosed phenotype in HIVAN is predominantly
      dependent on activation of the RAS.

PMID- 24892946
TI  - Alteration in the lower limit of autoregulation with elevations in cephalic
      venous pressure.
AB  - OBJECTIVES: Recent studies suggest that elevated intracranial pressure (ICP),
      created by hydrocephalus, can alter the lower limit of cerebrovascular
      autoregulation (LLA). Our objective in the present study was to determine if ICP
      elevation from cerebral venous outflow obstruction would result in comparable
      alterations in the LLA. METHODS: Anesthetized juvenile pigs were assigned to one
      of two groups: naive ICP (n  =  15) or high ICP (>20 mmHg; n  =  20). To elevate
      ICP through venous obstruction, a modified 5F esophageal balloon catheter was
      inserted via the right external jugular vein into the superior vena cava (SVC)
      and inflated to maintain an ICP of >20 mmHg. To calculate the LLA, gradual
      hypotension was induced by continuous hemorrhage from a catheter in the femoral
      vein. The LLA was determined by monitoring cortical laser Doppler flux (LDF).
      RESULTS: The naive and high ICP groups had LLAs of 45 mmHg (95% CI: 41-49 mmHg)
      and 71 mmHg (95% CI: 66-77 mmHg) respectively by LDF. The LLA was significantly
      different between the two groups and correlated significantly with ICP.
      DISCUSSION: Elevated ICP from cephalic venous engorgement leads to an increase in
      the LLA. These findings suggest that pathologic processes resulting in cephalic
      venous outflow obstruction and intracranial venous congestion can acutely elevate
      ICP and may place the brain at risk for impaired cerebrovascular autoregulation.

PMID- 24892945
TI  - MicroRNA-146a regulates human foetal femur derived skeletal stem cell
      differentiation by down-regulating SMAD2 and SMAD3.
AB  - MicroRNAs (miRs) play a pivotal role in a variety of biological processes
      including stem cell differentiation and function. Human foetal femur derived
      skeletal stem cells (SSCs) display enhanced proliferation and multipotential
      capacity indicating excellent potential as candidates for tissue engineering
      applications. This study has examined the expression and role of miRs in human
      foetal femur derived SSC differentiation along chondrogenic and osteogenic
      lineages. Cells isolated from the epiphyseal region of the foetal femur expressed
      higher levels of genes associated with chondrogenesis while cells from the foetal
      femur diaphyseal region expressed higher levels of genes associated with
      osteogenic differentiation. In addition to the difference in osteogenic and
      chondrogenic gene expression, epiphyseal and diaphyseal cells displayed distinct
      miRs expression profiles. miR-146a was found to be expressed by human foetal
      femur diaphyseal cells at a significantly enhanced level compared to epiphyseal
      populations and was predicted to target various components of the TGF-beta
      pathway. Examination of miR-146a function in foetal femur cells confirmed
      regulation of protein translation of SMAD2 and SMAD3, important TGF-beta and
      activin ligands signal transducers following transient overexpression in
      epiphyseal cells. The down-regulation of SMAD2 and SMAD3 following overexpression
      of miR-146a resulted in an up-regulation of the osteogenesis related gene RUNX2
      and down-regulation of the chondrogenesis related gene SOX9. The current findings
      indicate miR-146a plays an important role in skeletogenesis through attenuation
      of SMAD2 and SMAD3 function and provide further insight into the role of miRs in
      human skeletal stem cell differentiation modulation with implications therein for
      bone reparation. 

PMID- 24892948
TI  - Tunable morphology synthesis of LiFePO4 nanoparticles as cathode materials for
      lithium ion batteries.
AB  - Olivine LiFePO4 with nanoplate, rectangular prism nanorod and hexagonal prism
      nanorod morphologies with a short b-axis were successfully synthesized by a
      solvothermal in glycerol and water system. The influences of solvent composition
      on the morphological transformation and electrochemical performances of olivine
      LiFePO4 are systematically investigated by X-ray diffraction, scanning electron
      microscopy, transmission electron microscopy and galvanostatic charge-discharge
      tests. It is found that with increasing water content in solvent, the LiFePO4
      nanoplates gradually transform into hexagonal prism nanorods that are similar to
      the thermodynamic equilibrium shape of the LiFePO4 crystal. This indicates that
      water plays an important role in the morphology transformation of the olivine
      LiFePO4. The electrochemical performances vary significantly with the particle
      morphology. The LiFePO4 rectangular prism nanorods (formed in a glycerol-to-water
      ratio of 1:1) exhibit superior electrochemical properties compared with the other
      morphological particles because of their moderate size and shorter Li(+) ion
      diffusion length along the [010] direction. The initial discharge capacity of the
      LiFePO4@C with a rectangular prism nanorod morphology reaches to 163.8 mAh g(-1)
      at 0.2 C and over 75 mAh g(-1) at the high discharging rate of 20 C, maintaining
      good stability at each discharging rate. 

PMID- 24892949
TI  - Nanopillar lasers directly grown on silicon with heterostructure surface
      passivation.
AB  - Single-crystalline wurtzite InGaAs/InGaP nanopillars directly grown on a lattice
      mismatched silicon substrate are demonstrated. The nanopillar growth is in a core
      shell manner and gives a sharp, defect-free heterostructure interface. The InGaP
      shell provides excellent surface passivation effect for InGaAs nanopillars, as
      attested by 50-times stronger photoluminescence intensities and 5-times greater
      enhancements in the carrier recombination lifetimes, compared to the unpassivated
      ones. A record value of 16.8% internal quantum efficiency for InGaAs-based
      nanopillars was attained with a 50-nm-thick InGaP passivation layer. A room
      temperature optically pumped laser was achieved from single, as-grown InGaAs
      nanopillars on silicon with a record-low threshold. Superior material qualities
      of these InGaP-passivated InGaAs nanopillars indicate the possibility of
      realizing high-performance optoelectronic devices for photovoltaics, optical
      communication, semiconductor nanophotonics, and heterogeneous integration of III
      V materials on silicon. 

PMID- 24892947
TI  - Picosecond-resolved fluorescent probes at functionally distinct tryptophans
      within a thermophilic alcohol dehydrogenase: relationship of temperature
      dependent changes in fluorescence to catalysis.
AB  - Two single-tryptophan variants were generated in a thermophilic alcohol
      dehydrogenase with the goal of correlating temperature-dependent changes in local
      fluorescence with the previously demonstrated catalytic break at ca. 30  degrees
      C (Kohen et al., Nature 1999, 399, 496). One tryptophan variant, W87in, resides
      at the active site within van der Waals contact of bound alcohol substrate; the
      other variant, W167in, is a remote-site surface reporter located >25 A from the
      active site. Picosecond-resolved fluorescence measurements were used to analyze
      fluorescence lifetimes, time-dependent Stokes shifts, and the extent of
      collisional quenching at Trp87 and Trp167 as a function of temperature. A
      subnanosecond fluorescence decay rate constant has been detected for W87in that
      is ascribed to the proximity of the active site Zn(2+) and shows a break in
      behavior at 30  degrees C. For the remainder of the reported lifetime
      measurements, there is no detectable break between 10 and 50  degrees C, in
      contrast with previously reported hydrogen/deuterium exchange experiments that
      revealed a temperature-dependent break analogous to catalysis (Liang et al.,
      Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 9556). We conclude that the motions that
      lead to the rigidification of ht-ADH below 30  degrees C are likely to be
      dominated by global processes slower than the picosecond to nanosecond motions
      measured herein. In the case of collisional quenching of fluorescence by
      acrylamide, W87in and W167in behave in a similar manner that resembles free
      tryptophan in water. Stokes shift measurements, by contrast, show distinctive
      behaviors in which the active-site tryptophan relaxation is highly temperature
      dependent, whereas the solvent-exposed tryptophan's dynamics are temperature
      independent. These data are concluded to reflect a significantly constrained
      environment surrounding the active site Trp87 that both increases the magnitude
      of the Stokes shift and its temperature-dependence. The results are discussed in
      the context of spatially distinct differences in enthalpic barriers for protein
      conformational sampling that may be related to catalysis. 

PMID- 24892950
TI  - A more generalizable method to evaluate changes in health care costs with changes
      in health risks among employers of all sizes.
AB  - The objective of this study was to estimate the association between changes in
      health care expenditures relative to changes in health risk status for employers
      of all sizes. Repeat health risk assessments (HRAs) were obtained from 50,005
      employees and spouses with 2 years of health plan enrollment, and from 37,559
      employees and spouses with 3 years of enrollment in employer-sponsored medical
      coverage. Changes in health care expenditures were measured from the year before
      completion of the first HRA to the years before and after the completion of the
      second HRA. Propensity score weighting was used to adjust for those who did not
      repeat the HRA so results could be extrapolated to the larger population.
      Propensity score weighted multiple regression analyses were used to estimate the
      relationship between changes in health care expenditures with changes in risk
      status for 9 risk categories. Significantly higher health care expenditures were
      associated with those who moved from low risk to medium or high risk, compared to
      those who remained low risk. Expenditure reductions estimated for those who
      improved their health status from high risk to medium or low risk were not
      statistically significant. This study is unique because of its large sample size,
      its use of data from a wide range of employer sizes, and its efforts to extend
      generalizability to those who did not complete both HRAs. These results
      demonstrate that the potential for short-term health care savings may be greater
      for programs that help maintain low risk than for programs focused on risk
      reduction.

PMID- 24892951
TI  - Influence of multiple infection and relatedness on virulence: disease dynamics in
      an experimental plant population and its castrating parasite.
AB  - The level of parasite virulence, i.e., the decrease in host's fitness due to a
      pathogen, is expected to depend on several parameters, such as the type of the
      disease (e.g., castrating or host-killing) and the prevalence of multiple
      infections. Although these parameters have been extensively studied
      theoretically, few empirical data are available to validate theoretical
      predictions. Using the anther smut castrating disease on Silene latifolia caused
      by Microbotryum lychnidis-dioicae, we studied the dynamics of multiple infections
      and of different components of virulence (host death, non-recovery and percentage
      of castrated stems) during the entire lifespan of the host in an experimental
      population. We monitored the number of fungal genotypes within plants and their
      relatedness across five years, using microsatellite markers, as well as the rates
      of recovery and host death in the population. The mean relatedness among
      genotypes within plants remained at a high level throughout the entire host
      lifespan despite the dynamics of the disease, with recurrent new infections.
      Recovery was lower for plants with multiple infections compared to plants
      infected by a single genotype. As expected for castrating parasites, M. lychnidis
      dioicae did not increase host mortality. Mortality varied across years but was
      generally lower for plants that had been diseased the preceding year. This is one
      of the few studies to have empirically verified theoretical expectations for
      castrating parasites, and to show particularly i) that castrated hosts live
      longer, suggesting that parasites can redirect resources normally used in
      reproduction to increase host lifespan, lengthening their transmission phase, and
      ii) that multiple infections increase virulence, here in terms of non-recovery
      and host castration. 

PMID- 24892952
TI  - Micro-computed tomography derived anisotropy detects tumor provoked deviations in
      bone in an orthotopic osteosarcoma murine model.
AB  - Radiographic imaging plays a crucial role in the diagnosis of osteosarcoma.
      Currently, computed-tomography (CT) is used to measure tumor-induced osteolysis
      as a marker for tumor growth by monitoring the bone fractional volume. As most
      tumors primarily induce osteolysis, lower bone fractional volume has been found
      to correlate with tumor aggressiveness. However, osteosarcoma is an exception as
      it induces osteolysis and produces mineralized osteoid simultaneously. Given that
      competent bone is highly anisotropic (systematic variance in its architectural
      order renders its physical properties dependent on direction of load) and that
      tumor induced osteolysis and osteogenesis are structurally disorganized relative
      to competent bone, we hypothesized that MUCT-derived measures of anisotropy could
      be used to qualitatively and quantitatively detect osteosarcoma provoked
      deviations in bone, both osteolysis and osteogenesis, in vivo. We tested this
      hypothesis in a murine model of osteosarcoma cells orthotopically injected into
      the tibia. We demonstrate that, in addition to bone fractional volume, MUCT
      derived measure of anisotropy is a complete and accurate method to monitor
      osteosarcoma-induced osteolysis. Additionally, we found that unlike bone
      fractional volume, anisotropy could also detect tumor-induced osteogenesis. These
      findings suggest that monitoring tumor-induced changes in the structural property
      isotropy of the invaded bone may represent a novel means of diagnosing primary
      and metastatic bone tumors. 

PMID- 24892953
TI  - Setdb2 controls convergence and extension movements during zebrafish gastrulation
      by transcriptional regulation of dvr1.
AB  - As the primary driving forces of gastrulation, convergence and extension (C&E)
      movements lead to a medio-lateral narrowing and an anterior-posterior elongation
      of the embryonic body axis. Histone methylation as a post-translational
      modification plays a critical role in early embryonic development, but its
      functions in C&E movements remain largely unknown. Here, we show that the setdb2
      dvr1 transcriptional cascade plays a critical role in C&E movements during
      zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein
      possessing a potential histone H3K9 methyltransferase activity, induced abnormal
      C&E movements, resulting in anterior-posterior shortening and medio-lateral
      expansion of the embryonic axis, as well as abnormal notochord cell polarity.
      Furthermore, we found that Setdb2 functions through fine-tuning the expression of
      dvr1, a ligand of the TGF-beta superfamily, to an appropriate level to ensure
      proper C&E movements in a non-cell-autonomous manner. In addition, both
      overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at
      epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E
      movements and acts by modulating the expression level of dvr1, suggesting that
      Dvr1 acts as a direct and essential mediator for C&E cell movements. 

PMID- 24892954
TI  - Prognostic differences across sexes in melanoma patients: what has changed from
      the past?
AB  - Differences across the sexes include epidemiological trends, distribution of
      clinical features and prognostic relevance in melanoma patients. The aims of this
      single-institution hospital-based cohort study were as follows: to assess the
      trends over time of the male/female ratio; to analyse the clinicopathologic
      features according to sex and their modifications following the introduction in
      1999 of sentinel lymph node biopsy; to ascertain the metastatic pathways across
      sexes and the prognostic role of sex in the disease-free interval (DFI), disease
      specific survival (DSS) and survival after recurrence. The patient population
      included 4310 stage I-II melanoma patients, diagnosed, treated and followed up in
      our institution from 1975. Patients were divided into two groups on the basis of
      the introduction of sentinel lymph node biopsy in 1999. A female prevalence was
      observed until 1999; thereafter, the male/female ratio approached 1 (period 1999
      2003), with a subsequent increasing trend suggesting a potential male prevalence.
      Longer DFI and DSS were observed after 1999 and men showed greater improvement
      compared with women. In multivariate analyses, sex showed a lower impact on DFI
      and survival after recurrence following the introduction on sentinel lymph node
      biopsy. No sex-related differences in terms of DSS were observed before and after
      1999 among patients with melanoma located on the trunk. However, among patients
      with primary lesions not located on the trunk, sex maintained a significant
      prognostic role in both groups. The results of this study suggest that in the
      last few years, the prognosis of men could have improved more than that in women.
      The changing surgical/therapeutic interventions can influence sex disparities in
      melanoma. 

PMID- 24892955
TI  - Reproducibility of self-reported melanoma risk factors in melanoma patients.
AB  - As melanoma researchers continue to investigate environmental and lifestyle
      related risk factors, questionnaire data remain important. The reproducibility of
      a questionnaire on melanoma risk factors was investigated using a test-retest
      approach in 389 Dutch melanoma patients. In 2011, 389 melanoma patients filled
      out a questionnaire on melanoma risk factors twice. Test-retest reproducibility
      was assessed by calculating kappas (kappa), weighted kappas (kappaw), and
      intraclass correlation coefficients (ICCs) for categorical, ordinal, and
      continuous variables, respectively. Stratified analyses were carried out by sex,
      age group, education level, and time since diagnosis. The median time between the
      questionnaires was 31 days. The reproducibility was substantial for questions on
      phenotypic characteristics (kappa/kappaw/ICC=0.62-0.77), fair-to-substantial for
      sun exposure and sun protection behavior (kappa/kappaw/ICC=0.38-0.79), and
      moderate for sunburn history (kappa/kappaw=0.42-0.51). No clear differences were
      observed between men and women. Younger patients showed a better reproducibility
      in nine of the 29 questions compared with older patients and higher educated
      patients showed a better reproducibility in four of the 29 questions. Patients
      with a diagnosis shorter than 1.5 years ago had a better reproducibility in four
      out of 29 items compared with patients with a diagnosis 1.5-3.0 years ago. Our
      study showed that self-reported information on melanoma risk factors is fairly
      well reproducible. Although this does not guarantee validity, this type of
      questionnaire seems to be useful in research settings. The reproducibility is
      slightly better in young patients and patients with a higher education level,
      which can be taken into account when interpreting results from epidemiological
      studies. 

PMID- 24892956
TI  - Increased incidence of melanoma in situ in Denmark from 1997 to 2011: results
      from a nationwide population-based study.
AB  - The incidence of malignant melanoma has increased markedly among white
      populations in the recent decades. This may suggest that the incidence of
      melanoma in situ (MIS), the precursor of malignant melanoma, has also increased;
      however, few studies have assessed the incidence of MIS drawing on large
      population-based data sets. The present study aimed to assess MIS incidence
      trends in Denmark from 1997 to 2011. Data on MIS overall and on the histological
      subtypes superficial spreading MIS (SSM) and lentigo maligna (LM) were obtained
      from the Danish Nationwide Registry of Pathology. We calculated overall and age
      specific incidence rates for both sexes, age-adjusted according to the world
      standard population. The average annual percentage change (AAPC) and 95%
      confidence intervals were calculated using log-linear Poisson models. Among both
      sexes, a high continued increase in MIS incidence rates overall and in that of
      the histological subtypes SSM and LM were observed during the period from 1997 to
      2011. During this period, the age-adjusted MIS incidence rate increased from 2.6
      to 8.1 cases among women and from 1.4 to 5.6 cases among men per 100 000 person
      years. For both sexes, the highest AAPC in MIS incidence was observed during the
      most recent 5-year calendar period. A markedly higher AAPC was observed for SSM
      than for LM during the most recent 5-year calendar period for both sexes. The
      marked increase in incidence of MIS during the last 5 years of the period may
      indicate a growing awareness of skin cancer among the general Danish population
      and more frequent excision of suspicious skin lesions.

PMID- 24892957
TI  - Atypical Spitzoid neoplasms: a review of potential markers of biological behavior
      including sentinel node biopsy.
AB  - Atypical cutaneous melanocytic lesions, including those with Spitzoid features,
      can be difficult to categorize as benign or malignant. This can lead to
      suboptimal management, with potential adverse patient outcomes. Recent studies
      have enhanced knowledge of the molecular and genetic biology of these lesions
      and, combined with clinicopathological findings, is further defining their
      biological spectrum, classification, and behavior. Sentinel node biopsy provides
      important prognostic information in patients with cutaneous melanoma, but its
      role in the management of melanocytic lesions of uncertain malignant potential
      (MELTUMP) is controversial. This paper examines the role of molecular testing and
      sentinel node biopsy in MELTUMPs, particularly atypical Spitzoid tumors.

PMID- 24892958
TI  - Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in
      metastasis of melanoma.
AB  - Melanoma is a highly aggressive skin cancer with increasing incidence worldwide.
      Long noncoding RNAs (lncRNAs), a group of nonprotein-coding transcripts longer
      than 200 nucleotides, are pervasively transcribed in the genome and are emerging
      as new players in tumorigenesis. The primary objective of this study was to
      investigate the role of six cancer-related lncRNAs in pairs of melanoma and
      adjacent normal tissues (ANTs). A total of 63 primary melanoma, paired ANTs, and
      metastatic lesions were collected in a Chinese population. Real-time PCR analysis
      was carried out to compare a series of cancer-related lncRNAs among primary
      melanoma tissues, ANTs, and metastatic lesions. In in-vitro studies, transwell
      migration assay was carried out to estimate the migration abilities of melanoma
      cells with different expression levels of urothelial carcinoma-associated 1
      (UCA1) or metastasis-associated lung adenocarcinoma transcript 1 (Malat-1)
      lncRNAs. We found that UCA1 and Malat-1 lncRNAs were markedly more increased in
      melanomas than in paired ANTs (P<0.05). Melanomas at later stages (stages 3-4)
      showed higher expression of UCA1 lncRNA than those at early stages (stages 1-2)
      (P=0.455). In melanomas with lymph node metastasis, the metastatic lesions had a
      relatively higher expression of Malat-1 lncRNA than in paired primary tumors
      (P=0.414). Knockdown of UCA1 or Malat-1 lncRNA could attenuate the migrational
      ability of melanoma cells in in-vitro studies. Increased expression of UCA1 and
      Malat-1 lncRNAs might have a correlation with melanoma metastasis. 

PMID- 24892959
TI  - In-vitro melanoma models: invasive growth is determined by dermal matrix and
      basement membrane.
AB  - A critical first step in the metastatic progression of cutaneous melanoma,
      invasive growth into the dermal compartment, would ideally be studied in the
      proper three-dimensional tissue microenvironment. In this study, we compared the
      growth and behavior of four melanoma cell lines originating from primary and
      metastatic human cutaneous melanomas (AN, RU, M14, and WK) in in-vitro human skin
      equivalents (HSEs) generated with four different dermal matrices: human
      fibroblast-seeded rat tail collagen, human fibroblast-derived matrix (FDM),
      noncellular human de-epidermized dermis (DED), and a novel fully cellular human
      DED with an intact pre-existent basement membrane. Melanoma cells showed
      proliferation in all HSEs, indicating that the microenvironment formed in all
      HSEs studied here allows the growth of melanoma cells in concert with epidermal
      keratinocytes for multiple weeks in vitro. Melanoma cells did not affect
      epidermal proliferation and terminal differentiation. Growth of melanoma cells in
      the dermal compartment, as a measure of invasive potential, differs markedly
      between the four types of in-vitro human melanoma models. Notably, the growth of
      melanoma cells in the dermal matrix was observed in all HSEs cultured with cell
      lines originating from metastatic melanoma, except for cDED-based HSEs, and the
      growth of melanoma cells of nonmetastatic origin was observed in the dermal
      compartment of FDM-based HSEs. Our results show that the type of dermal
      equivalent and the presence of an intact basement membrane should be taken into
      consideration when studying melanoma invasion using in-vitro HSEs. 

PMID- 24892961
TI  - Mechanistic studies of two-dimensional covalent organic frameworks rapidly
      polymerized from initially homogenous conditions.
AB  - Covalent organic frameworks (COFs) are periodic two- and three-dimensional (2D
      and 3D) polymer networks with high surface areas, low densities, and designed
      structures. Despite intense interest in framework materials, the nucleation and
      growth processes of COFs, and even of more established metal-organic frameworks
      (MOFs), are poorly understood. The kinetics of COF growth under varied reaction
      conditions provides mechanistic insight needed to improve their crystallinity and
      rationally synthesize new materials. Such kinetic measurements are unprecedented
      and difficult to perform on typical heterogeneous COF reaction mixtures. Here we
      synthesize 2D boronate ester-linked COF-5 under conditions in which the monomers
      are fully soluble. These homogeneous growth conditions provide equal or better
      material quality compared to any previous report and enable the first rigorous
      studies of the early stages of COF growth. COF-5 forms within minutes, and the
      precipitation rate is readily quantified from optical turbidity measurements. COF
      5 formation follows an Arrhenius temperature dependence between 60-90  degrees C
      with an activation energy of 22-27 kcal/mol. The measured rate law includes a
      second order in both boronic acid and catechol moieties, and inverse second order
      in MeOH concentration. A competitive monofunctional catechol slows COF-5
      formation but does not redissolve already precipitated COF, indicating both
      dynamic covalent bond formation and irreversible precipitation. Finally,
      stoichiometric H2O provides a 4-fold increase in crystallite domain areas,
      representing the first rational link between reaction conditions and material
      quality. 

PMID- 24892962
TI  - The severity of acute cellular rejection defined by Banff classification is
      associated with kidney allograft outcomes.
AB  - BACKGROUND: It is unclear if the severity or the timing of acute cellular
      rejection (ACR) defined by Banff classification 2009 is associated with graft
      survival. METHODS: Borderline changes, TCMR I (interstitial rejection), and TCMR
      II/III (vascular rejection) were defined as low, moderate, and high ACR severity,
      respectively. Approximately 270 patients who had at least one episode of ACR were
      enrolled, 270 biopsies were chosen which showed the highest ACR severity of each
      patient and were negative for donor-specific antibodies (DSA), C4d, and
      microcirculation changes (MC). Six months were used as the cutoff to define early
      and late ACR; 370 patients without biopsy posttransplantation were recruited in
      the control group. RESULTS: Up to 8-year posttransplantation, death-censored
      graft survival (DCGS) rates of control, borderline, TCMR I, and TCMR II/III
      groups were 97.6%, 93.3%, 79.6%, and 73.6% (log rank test, P<0.001); the control
      group had significantly higher DCGS rate than the three ACR groups (each pairwise
      comparison yields P<0.05). The DCGS rate of late ACR was significantly lower
      compared with early ACR (63.6% vs. 87.4%, P<0.001). Intimal arteritis (Banff v
      lesion) was an independent histologic risk factor correlated with long-term graft
      loss regardless of the timing of ACR. The v-lesions with minimal or high-grade
      tubulitis displayed similar graft survival (72.7% vs. 72.9%, P=0.96). CONCLUSION:
      All types of ACR affect long-term graft survival. Vascular or late ACR predict
      poorer graft survival; the extent of tubulointerstitial inflammation (TI) is of
      no prognostic significance for vascular rejection.

PMID- 24892963
TI  - Use of living donor liver grafts with double or triple arteries.
AB  - BACKGROUND: Hepatic grafts used in living donor liver transplantation (LDLT)
      sometimes have two or more arteries, in which surgeons are required to perform
      complex arterial reconstruction. The aim of the current study was to demonstrate
      whether selecting living donor liver grafts with double or triple arteries
      yielded the same outcomes as grafts with a single artery. METHODS: We
      retrospectively investigated the outcomes of LDLT focusing on the numbers of
      arteries on grafts. Four hundred forty-six cases of LDLT performed between
      October 1996 and October 2012 were retrospectively analyzed. The cases were
      divided into the following three groups according to the number of arteries on a
      graft: the single (n=331), the double (n=108), and the triple (n=7) groups.
      RESULTS: Artery-related complications occurred in five cases in the single group,
      two cases in the double group, and no case in the triple group. Although the
      overall graft survival was comparable among the three groups, there was a
      tendency of worsened graft survival and increased incidence of anastomotic
      biliary stricture after liver transplantation in right hepatic grafts with double
      arteries. CONCLUSIONS: The use of grafts with double or triple arteries yielded
      favorable outcomes with minimum artery-related complications compared with grafts
      with a single artery. However, the use of right hepatic grafts with double
      arteries is discouraging in the current study.

PMID- 24892964
TI  - Herpes zoster-attributable resource utilization and cost burden in patients with
      solid organ transplant.
AB  - OBJECTIVES: To evaluate health-care utilization and costs attributable to herpes
      zoster (HZ) within a population of patients with solid organ transplant (SOT).
      METHODS: Using administrative claims data, a commercially/Medicare-insured
      population of patients with SOT between January 1, 1999, and January 1, 2007, and
      a Medicaid population between January 1, 1999, and January 1, 2006, were
      identified. Each patient group was screened to select patients with claims of SOT
      with an incident diagnosis of HZ and continuous enrollment for the 6 months prior
      and 3 months subsequent to the incident HZ. Controls were selected from group of
      SOT patients without claims of HZ using a propensity score matching process.
      Descriptive analyses were performed to quantify health-care utilization and costs
      attributable to HZ. Multivariate analyses were used to estimate HZ-attributable
      costs adjusted by demographic and clinical variables. RESULTS: A total of 205
      commercially/Medicare-insured matched pairs and 136 Medicaid matched pairs were
      selected. Mean age in the commercial/Medicare SOT-HZ population was 56.9 years,
      and that in the Medicaid population was 42.5 years. The majority of HZ patients
      were diagnosed within 2 years of evidence of SOT. The unadjusted differences in
      total HZ-attributable health-care costs were $4762 and $6705 for
      commercial/Medicare-insured and Medicaid patients, respectively (P=0.176 and
      P=0.003, respectively) and were largely driven by hospitalization costs. Adjusted
      incremental costs in the SOT-HZ commercial/Medicare-insured patients were $5335
      (P<0.001), and that in noncapitated Medicaid patients were $3711 (P<0.001).
      CONCLUSION: The occurrence of HZ in patients immunocompromised by SOT
      significantly increased health-care utilization and costs.

PMID- 24892965
TI  - Impaired innate immune function associated with fecal supernatant from Crohn's
      disease patients: insights into potential pathogenic role of the microbiome.
AB  - BACKGROUND: Although a dysbiosis of the intestinal microbiome plays a role in the
      pathogenesis of Crohn's disease (CD), the functional implication is unclear. We
      sought to determine the influence of fecal supernatant from patients with CD on
      innate immune function in neutrophil, macrophage, and epithelial cells.
      Metabolomic analysis was subsequently performed in an attempt to identify
      potential compounds responsible for the effects identified. METHODS: In the fecal
      samples from 11 pediatric patients with CD and 10 healthy controls, 16S ribosomal
      and metabolomic analyses were performed. We evaluated the effect of preincubation
      with fecal supernatant on neutrophil, macrophage, epithelial cell survival,
      superoxide production, bacterial invasion, and/or bactericidal function using
      gentamicin protection assay. Ten substances identified as most elevated in CD
      compared with control samples by metabolomic analysis were similarly tested for
      effect on bactericidal function. RESULTS: There were no statistically significant
      differences in microbial membership in fecal samples from patients with CD
      compared with healthy controls. However, bactericidal function was impaired in
      neutrophils and monocytes preincubated with supernatant from fecal samples from
      patients with CD. Although levels of many metabolites were noted to be altered in
      samples from patients with CD, the combination of the 10 most elevated compounds
      failed to demonstrate any effect on neutrophil bactericidal capacity.
      CONCLUSIONS: Fecal supernatant from patients with CD impairs intracellular
      bactericidal activity in neutrophils and macrophages. The functional consequences
      of the intestinal microbiome and its associated secreted products on innate
      immune function may be more critical than microbial membership in understanding
      the pathophysiology of CD.

PMID- 24892966
TI  - Fibrosis in ulcerative colitis: mechanisms, features, and consequences of a
      neglected problem.
AB  - Chronic intestinal inflammation and impaired tissue repair leading to intestinal
      fibrosis are a commonly observed complication in inflammatory bowel disease. This
      is particularly true for small bowel Crohn's disease. However, the development of
      fibrosis in ulcerative colitis has remained largely unexplored. This is
      surprising, given knowledge about its prevalence for decades, well described
      histopathologic features of fibrotic and stricturing ulcerative colitis, the
      relevance of the extracellular matrix for intestinal inflammation and fibrosis,
      and the clinical impact of fibrosis on stricture formation, motility, and the
      necessary discrimination from colonic malignancy. This systematic review
      summarizes the current knowledge of ulcerative colitis-related fibrosis,
      including epidemiology, basic mechanisms, histopathology, and clinical
      implications.

PMID- 24892967
TI  - Lipid monolayers and adsorbed polyelectrolytes with different degrees of
      polymerization.
AB  - Polystyrene sulfonate (PSS) of different molecular weight M(w) is adsorbed to
      oppositely charged DODAB monolayers from dilute solutions (0.01 mmol/L). PSS
      adsorbs flatly in a lamellar manner, as is shown by X-ray reflectivity and
      grazing incidence diffraction (exception: PSS with M(w) below 7 kDa adsorbs
      flatly disordered to the liquid expanded phase). The surface coverage and the
      separation of the PSS chains are independent of PSS M(w). On monolayer
      compression, the surface charge density increases by a factor of 2, and the
      separation of the PSS chains decreases by the same factor. Isotherms show that on
      increase of PSS M(w) the transition pressure of the LE/LC (liquid expanded/liquid
      condensed) phase transition decreases. When the contour length exceeds the
      persistence length (21 nm), the transition pressure is low and constant. For low
      M(w) PSS (<7 kDa) the LE/LC transition of the lipids and the disordered/ordered
      transition of adsorbed PSS occur simultaneously, leading to a maximum in the
      contour length dependence of the transition enthalpy. These findings show that
      lipid monolayers at the air/water interface are a suitable model substrate with
      adjustable surface charge density to study the equilibrium conformation of
      adsorbed polyelectrolytes as well as their interactions with a model membrane.

PMID- 24892968
TI  - Lingual frenotomy for breastfeeding difficulties: a prospective follow-up study.
AB  - INTRODUCTION: Breastfeeding difficulties are sometimes attributable to tongue-tie
      with short-term relief after frenotomy. Limited follow-up is available, and
      predictors for nonsuccessful frenotomy have not yet been found. PATIENTS AND
      METHODS: We recruited 264 mother-infant dyads who underwent lingual frenotomy for
      breastfeeding difficulties. Data regarding the indications, anatomy of the
      tongue, and the response of the infant were noted by the physician. Mothers were
      contacted by telephone at 2 weeks, 3 months, and 6 months after frenotomy to
      answer a questionnaire. RESULTS: Two weeks after frenotomy, 89% of mothers were
      still breastfeeding. An improvement in breastfeeding was reported by three
      quarters of the mothers, but, unexpectedly, 3% reported worsening. At 3 and 6
      months after the procedure, 68% and 56% of mothers were still breastfeeding,
      respectively. We could not find any predictor to indicate those infants in whom
      breastfeeding would not improve. CONCLUSIONS: There are favorable long-term
      effects of frenotomy on breastfeeding. Lingual frenotomy does not always
      alleviate breastfeeding difficulties, and rarely worsening ensues. We could not
      find any predictor for successful breastfeeding after frenotomy. We speculate
      that because the procedure is minor, in the event of breastfeeding difficulties,
      lingual frenotomy should be considered as an effective tool to assist in long
      term breastfeeding.

PMID- 24892971
TI  - Deep eutectic solvents: sustainable media for nanoscale and functional materials.
AB  - Deep eutectic solvents (DESs) represent an alternative class of ionic fluids
      closely resembling room-temperature ionic liquids (RTILs), although, strictly
      speaking, they are distinguished by the fact that they also contain an organic
      molecular component (typically, a hydrogen bond donor like a urea, amide, acid,
      or polyol), frequently as the predominant constituent. Practically speaking, DESs
      are attractive alternatives to RTILs, sharing most of their remarkable qualities
      (e.g., tolerance to humidity, negligible vapor pressure, thermostability, wide
      electrochemical potential windows, tunability) while overcoming several
      limitations associated with their RTIL cousins. Particularly, DESs are typically,
      less expensive, more synthetically accessible (typically, from bulk commodity
      chemicals using solvent/waste-free processes), nontoxic, and biodegradable. In
      this Account, we provide an overview of DESs as designer solvents to create well
      defined nanomaterials including shape-controlled nanoparticles, electrodeposited
      films, metal-organic frameworks, colloidal assemblies, hierarchically porous
      carbons, and DNA/RNA architectures. These breakthroughs illustrate how DESs can
      fulfill multiple roles in directing chemistry at the nanoscale: acting as
      supramolecular template, metal/carbon source, sacrificial agent (e.g., ammonia
      release from urea), and/or redox agent, all in the absence of formal stabilizing
      ligand (here, solvent and stabilizer are one and the same). The ability to tailor
      the physicochemical properties of DESs is central to controlling their
      interfacial behavior. The preorganized "supramolecular" nature of DESs provides a
      soft template to guide the formation of bimodal porous carbon networks or the
      evolution of electrodeposits. A number of essential parameters (viscosity,
      polarity, surface tension, hydrogen bonding), plus coordination with
      solutes/surfaces, all play significant roles in modulating species reactivity and
      mass transport properties governing the genesis of nanostructure. Furthermore,
      DES components may modulate nucleation and growth mechanisms by charge
      neutralization, modification of reduction potentials (or chemical activities),
      and passivation of particular crystal faces, dictating growth along preferred
      crystallographic directions. Broad operational windows for electrochemical
      reactions coupled with their inherent ionic nature facilitate the
      electrodeposition of alloys and semiconductors inaccessible to classical means
      and the use of cosolvents or applied potential control provide under-explored
      strategies for mediating interfacial interactions leading to control over film
      characteristics. The biocompatibility of DESs suggests intriguing potential for
      the construction of biomolecular architectures in these novel media. It has been
      demonstrated that nucleic acid structures can be manipulated in the ionic,
      crowded, dehydrating (low water activity) DES environment-including the adoption
      of duplex helical structures divergent from the canonical B form and parallel G
      quadruplex DNA persisting near water's boiling point-challenging the
      misconception that water is a necessity for maintenance of nucleic acid
      structure/functionality and suggesting an enticing trajectory toward DNA/RNA
      based nanocatalysis within a strictly anhydrous medium. DESs offer tremendous
      opportunities and open intriguing perspectives for generating sophisticated
      nanostructures within an anhydrous or low-water medium. We conclude this Account
      by offering our thoughts on the evolution of the field, pointing to areas of
      clear and compelling utility which will surely see fruition in the coming years.
      Finally, we highlight a few hurdles (e.g., need for a universal nomenclature,
      absence of water-immiscible, oriented-phase, and low-viscosity DESs) which, once
      navigated, will hasten progress in this area.

PMID- 24892970
TI  - Oblique incidence reflectometry: optical models and measurements using a side
      viewing gradient index lens-based endoscopic imaging system.
AB  - A side-viewing, 2.3-mm diameter oblique incidence reflectometry endoscope has
      been designed to obtain optical property measurements of turbid samples. Light
      from a single-mode fiber is relayed obliquely onto the tissue with a gradient
      index lens-based distal optics assembly and the resulting diffuse reflectance
      profile is imaged and collected with a 30,000 element, 0.72 mm clear aperture
      fiber bundle. Sampling the diffuse reflectance in two-dimensions allows for
      fitting of the reflected intensity profile to a well-known theoretical model,
      permitting the extraction of both absorption and reduced scattering coefficients
      of the tissue sample. Models and measurements of the endoscopic imaging system
      are presented in tissue phantoms and in vivo mouse colon, verifying the
      endoscope's capabilities to accurately measure effective attenuation coefficient
      and differentiate diseased from normal colon.

PMID- 24892972
TI  - The HELIX Project: tracking the exposome in real time.

PMID- 24892973
TI  - Copper-catalyzed direct trifluoromethylthiolation of benzylic C-H bonds via
      nondirected oxidative C(sp3)-H activation.
AB  - A copper-catalyzed trifluoromethylthiolation of benzylic sp(3) C-H bonds was
      developed via nondirected oxidative C-H activation using readily prepared and
      stable AgSCF3. This reaction provides a novel and straightforward method for the
      preparation of various benzyl trifluoromethyl sulfides. 

PMID- 24892974
TI  - Selective intracellular delivery of proteasome inhibitors through pH-sensitive
      polymeric micelles directed to efficient antitumor therapy.
AB  - The ubiquitin-proteasome system is central in the regulation of cellular proteins
      controlling cell cycle progression and apoptosis, drawing much interest for
      developing effective targeted cancer therapies. Herein, we developed a novel pH
      responsive polymeric-micelle-based carrier system to effectively deliver the
      proteasome inhibitor MG132 into cancer cells. MG132 is covalently bound to the
      block copolymer composed of polyethylene glycol (PEG) and polyaspartate through
      an acid-labile hydrazone bond. This bond is stable at physiological condition,
      but hydrolytically degradable in acidic compartments in the cell, such as late
      endosomes and lysosomes, and thus, it was used for controlled release of MG132
      after EPR-mediated preferential accumulation of the micelles into the tumor.
      MG132-loaded micelles have monodispersed size distribution with an average
      diameter of 45nm, and critical micelle concentration is well below 10(-7)M. In
      vitro studies against several cancer cell lines confirmed that MG132-loaded
      micelles retained the cytotoxic effect, and this activity was indeed due to the
      inhibition of proteasome by released MG132 from the micelles. Real-time in vitro
      confocal-microscopy experiments clearly indicated that MG132-conjugated micelles
      disintegrated only inside the target cells. By intravital confocal micro
      videography, we also confirmed the prolonged circulation of MG132 loaded micelles
      in the bloodstream, which lead to tumor specific accumulation of micelles, as
      confirmed by in vivo imaging 24h after injection. These micelles showed
      significantly lower in vivo toxicity than free MG132, while achieving remarkable
      antitumor effect against a subcutaneous HeLa-luc tumor model. Our findings create
      a paradigm for future development of polymeric-micelle-based carrier system for
      other peptide aldehyde type proteasome inhibitors to make them effective cohort
      of the existing cancer therapeutic regiments. 

PMID- 24892975
TI  - Selective photosensitizer delivery into plasma membrane for effective
      photodynamic therapy.
AB  - Subcellular localization of photosensitizers (PSs) determines the therapeutic
      efficacy in the photodynamic therapy. However, among the subcellular
      compartments, there has been little effort to deliver the PSs selectively into
      the plasma membrane and examine the phototherapeutic efficacy of membrane
      localized PSs. Here, we developed a liposomal delivery system to localize the
      hydrophobic PSs selectively into the plasma membrane. The membrane fusogenic
      liposomes (MFLs), the membrane of which is engineered to fuse with the plasma
      membrane, was prepared for the membrane localization of PSs. The phototherapeutic
      efficacy of cells treated with ZnPc-loaded MFLs was superior over that of cells
      treated with ZnPc-loaded non-fusogenic liposomes, which is the conventional
      liposomal formulation that delivers the PSs into the intracellular compartments
      via endocytosis. The membrane localization of ZnPc molecules led to rapid
      membrane disruption upon irradiation and subsequent necrosis-like cell death. The
      membrane-localized generation of reactive oxygen species in the cells treated
      with ZnPc-loaded MFLs was likely to account for the effective disruption of
      plasma membrane. Thus, this work provides a novel delivery method to localize the
      PSs selectively into the plasma membrane with the enhanced phototherapeutic
      efficacy. 

PMID- 24892976
TI  - Controlled release of free doxorubicin from peptide-drug conjugates by drug
      loading.
AB  - Covalent modification of a drug with a peptide moiety has been extensively used
      as an effective strategy to improve the drug's therapeutic outcome. One important
      consideration in the design of such a prodrug is the release of the free drug
      from the covalently bound form in a desired fashion. In most cases, the free drug
      release rate is controlled by the use of various chemical linkers that bridge the
      drug to the auxiliary segment. We report here that the degree of drug conjugation
      per peptide could also regulate the drug release in addition to its apparent
      effect on drug loading of the resulting conjugates. In this work, we synthesized
      three peptide-drug conjugates (NTD, d-NTD and q-NTD) in which the cell
      penetrating peptide Tat is covalently connected to one, two, or four doxorubicin,
      respectively, through a cathepsin B degradable tetrapeptide linker (-Gly-Phe-Leu
      Gly-). We found that the number of doxorubicin within the conjugate impacts the
      release of doxorubicin in a significant way, with q-NTD showing the slowest
      release rate while NTD showing the fastest release rate. Our cellular uptake
      experiments reveal that q-NTD accumulated most effectively within cancer cells
      while NTD shows the lowest intracellular accumulation concentration.
      Interestingly, our cell viability assessment using a SRB assay reveals that d-NTD
      is the most potent conjugate against HepG2 human liver cancer cells. These
      results suggest that intracellular accumulation efficiency and the free drug
      release rate are two important factors that determine the in vitro efficacy of
      drug conjugates. To further validate this conclusion, we conjugated a short
      hydrocarbon onto the NTD to improve its cellular uptake, and found that the
      resulting conjugate, C16NTD, exhibited comparable intracellular accumulation as
      the q-NTD conjugate but superior anticancer activity due to its more effective
      release of free doxorubicin. 

PMID- 24892977
TI  - An artifact in LC-MS/MS measurement of glutamine and glutamic acid: in-source
      cyclization to pyroglutamic acid.
AB  - Advances in metabolomics, particularly for research on cancer, have increased the
      demand for accurate, highly sensitive methods for measuring glutamine (Gln) and
      glutamic acid (Glu) in cell cultures and other biological samples. N-terminal Gln
      and Glu residues in proteins or peptides have been reported to cyclize to
      pyroglutamic acid (pGlu) during liquid chromatography (LC)-mass spectrometry (MS)
      analysis, but cyclization of free Gln and Glu to free pGlu during LC-MS analysis
      has not been well-characterized. Using an LC-MS/MS protocol that we developed to
      separate Gln, Glu, and pGlu, we found that free Gln and Glu cyclize to pGlu in
      the electrospray ionization source, revealing a previously uncharacterized
      artifact in metabolomic studies. Analysis of Gln standards over a concentration
      range from 0.39 to 200 MUM indicated that a minimum of 33% and maximum of almost
      100% of Gln was converted to pGlu in the ionization source, with the extent of
      conversion dependent on fragmentor voltage. We conclude that the sensitivity and
      accuracy of Gln, Glu, and pGlu quantitation by electrospray ionization-based mass
      spectrometry can be improved dramatically by using (i) chromatographic conditions
      that adequately separate the three metabolites, (ii) isotopic internal standards
      to correct for in-source pGlu formation, and (iii) user-optimized fragmentor
      voltage for acquisition of the MS spectra. These findings have immediate impact
      on metabolomics and metabolism research using LC-MS technologies. 

PMID- 24892978
TI  - Evaluation of vascular effect of Photodynamic Therapy in chorioallantoic membrane
      using different photosensitizers.
AB  - Photodynamic Therapy (PDT) is a local treatment that requires a photosensitizing
      agent, light and molecular oxygen. With appropriate illumination, the
      photosensitizer is excited and produces singlet oxygen that is highly reactive
      and cytotoxic. Tumor vascular network is essential for the tumor growth and the
      understanding of vascular response mechanisms enables an improvement in the PDT
      protocol for cancer treatment. Compounds of porphyrin (Photogem(r)) and chlorin
      (Photodithazine(r)) were the photosensitizers tested. The incubation times varied
      from 20 to 80 min and the concentration ranged between 0.1 and 100 MUg/cm(2).
      Different light doses were used between 4.8 and 40 J/cm(2) with irradiance
      varying between 80 and 100 mW/cm(2). The light dose of 30 J/cm(2) was used in the
      intravenous photosensitizer application. The membrane images were made from 0 to
      300 min after treatment. The vascular response was evaluated by the average
      vessel area. Different responses was observed depending on the photosensitizer
      concentration and administration form. Intravenous application has been more
      efficient to produce vessel constriction and the most pronounced effect was
      observed for the chlorin.

PMID- 24892979
TI  - Crowded milieu prevents fibrillation of hen egg white lysozyme with retention of
      enzymatic activity.
AB  - Molten globule state plays a crucial role in the amyloidogenesis of several
      proteins. Hen egg white lysozyme (HEWL) acquires a molten globule state at
      alkaline pH (12.75). Our study reveals a significant inhibitory effect of high
      molecular weight polyethylene glycols (PEG) (PEG 20000 and PEG 35000) against
      alkali-salt mediated fibrillation of HEWL. Native state of HEWL is stabilized in
      the presence of PEGs accompanied by a decrease in the beta-sheet content.
      Enzymatic activity of HEWL is mostly retained in the presence of polyethylene
      glycols. The comparable hydrodynamic radius (Rh) of PEG 20000 and native HEWL is
      central reason to the greater inhibitory potency of PEG 20000 against HEWL
      fibrillation. 

PMID- 24892980
TI  - Synthesis and biological activities of novel pleuromutilin derivatives with a
      substituted thiadiazole moiety as potent drug-resistant bacteria inhibitors.
AB  - A series of novel pleuromutilin derivatives possessing thiadiazole moieties were
      synthesized via acylation reactions under mild conditions. The in vitro
      antibacterial activities of the derivatives against methicillin-resistant
      Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis,
      Escherichia coli, and Streptococcus agalactiae were tested by the agar dilution
      method and Oxford cup assay. The majority of the tested compounds displayed
      moderate antibacterial activities. Importantly, the three compounds with amino or
      tertiary amine groups in their side chains, 11, 13b, and 15c, were the most
      active antibacterial agents. Docking experiments carried out on the peptidyl
      transferase center (PTC) of 23S rRNA proved that there is a reasonable direct
      correlation between the binding free energy (DeltaGb, kcal/mol) and the
      antibacterial activity. Moreover, the pharmacokinetic profiles of 11 and 15c in
      rat were characterized by moderate clearance and oral bioavailability. 

PMID- 24892981
TI  - A Comparison of Manifestations and Impact of Reassurance Seeking among Japanese
      Individuals with OCD and Depression.
AB  - BACKGROUND: One of the most common interpersonal reactions to threat and anxiety
      is to seek reassurance from a trusted person. The Reassurance Seeking
      Questionnaire (ReSQ) measures several key aspects of reassurance seeking
      behaviour, including frequency, trust of sources, intensity, carefulness, and the
      emotional consequences of reassurance seeking. AIMS: The current study compares
      patterns and consequences of reassurance seeking in obsessive-compulsive disorder
      (OCD) and depression. METHOD: ReSQ scores were compared for three groups: 32
      individuals with OCD, 17 individuals with depression, and 24 healthy comparison
      participants. RESULTS: We found that individuals with OCD tended to seek
      reassurance more intensely and employ self-reassurance more frequently than
      individuals with depression or healthy participants, and that if reassurance was
      not provided, they tended to feel a greater urge to seek additional reassurance.
      CONCLUSIONS: This study is the first to quantitatively elucidate differences in
      reassurance seeking between OCD and depression.

PMID- 24892984
TI  - Synthesis, structure, luminescence, and magnetic properties of a single-ion
      magnet "mer"-[tris(N-[(imidazol-4-yl)-methylidene]-DL
      phenylalaninato)terbium(III) and related "fac"-DL-alaninato derivative.
AB  - Two Tb(III) complexes with the same N6O3 donor atoms but different coordination
      geometries, "fac"-[Tb(III)(HL(DL-ala))3].7H2O (1) and "mer"-[Tb(III)(HL(DL
      phe))3].7H2O (2), were synthesized, where H2L(DL-ala) and H2L(DL-phe) are N
      [(imidazol-4-yl)methylidene]-DL-alanine and -DL-phenylalanine, respectively. Each
      Tb(III) ion is coordinated by three electronically mononegative NNO tridentate
      ligands to form a coordination geometry of a tricapped trigonal prism. Compound 1
      consists of enantiomers "fac"-[Tb(III)(HL(D-ala))3] and "fac"-[Tb(III)(HL(L
      ala))3], while 2 consists of "mer"-[Tb(III)(HL(D-phe))2(HL(L-phe))] and "mer"
      [Tb(III)(HL(D-phe))(HL(L-phe))2]. Magnetic data were analyzed by a spin
      Hamiltonian including the crystal field effect on the Tb(III) ion (4f(8), J = 6,
      S = 3, L = 3, gJ = 3/2, (7)F6). The Stark splitting of the ground state (7)F6 was
      evaluated from magnetic analysis, and the energy diagram pattern indicated easy
      plane and easy-axis (Ising type) magnetic anisotropies for 1 and 2, respectively.
      Highly efficient luminescences with Phi = 0.50 and 0.61 for 1 and 2,
      respectively, were observed, and the luminescence fine structure due to the (5)D4
      -> (7)F6 transition is in good accordance with the energy diagram determined from
      magnetic analysis. The energy diagram of 1 shows an approximate single-well
      potential curve, whereas that of 2 shows a double- or quadruple-well potential
      within the (7)F6 multiplets. Complex 2 displayed an onset of the out-of-phase
      signal in alternating current (ac) susceptibility at a direct current bias field
      of 1000 Oe on cooling down to 1.9 K. A slight frequency dependence was recorded
      around 2 K. On the other hand, 1 did not show any meaningful out-of-phase ac
      susceptibility. Pulsed-field magnetizations of 1 and 2 were measured below 1.6 K,
      and only 2 exhibited magnetic hysteresis. This finding agrees well with the
      energy diagram pattern from crystal field calculation on 1 and 2. DFT calculation
      allowed us to estimate the negative charge distribution around the Tb(III) ion,
      giving a rationale to the different magnetic anisotropies of 1 and 2.

PMID- 24892983
TI  - In vivo sex differences in leukotriene biosynthesis in zymosan-induced
      peritonitis.
AB  - Leukotrienes (LTs) are 5-lipoxygenase (5-LO) metabolites which are implicated in
      sex-dependent inflammatory diseases (asthma, autoimmune diseases, etc.). We have
      recently reported sex differences in LT biosynthesis in in vitro models such as
      human whole blood, neutrophils and monocytes, due to down-regulation of 5-LO
      product formation by androgens. Here we present evidences for sex differences in
      LT synthesis and related inflammatory reactions in an in vivo model of
      inflammation (mouse zymosan-induced peritonitis). On the cellular level,
      differential 5-LO subcellular compartmentalization in peritoneal macrophages (PM)
      from male and female mice might be the basis for these differences. Sex
      differences in vascular permeability and neutrophil recruitment (cell number and
      myeloperoxidase activity) into peritoneal cavity were evident upon
      intraperitoneal zymosan injection, with more prominent responses in female mice.
      This was accompanied by higher levels of LTC4 and LTB4 in peritoneal exudates of
      female compared to male mice. Interestingly, LT peritoneal levels in
      orchidectomized mice were higher than in sham male mice. In accordance with the
      in vivo results, LT formation in stimulated PM from female mice was higher than
      in male PM, accompanied by alterations in 5-LO subcellular localization. The
      increased formation of LTC4 in incubations of PM from orchidectomized mice
      confirms a role of sex hormones. In conclusion, sex differences observed in LT
      biosynthesis during peritonitis in vivo may be related, at least in part, to a
      variant 5-LO localization in PM from male and female mice. 

PMID- 24892985
TI  - NqA: an R-based algorithm for the normalization and analysis of microRNA
      quantitative real-time polymerase chain reaction data.
AB  - In this note, we propose an R function named NqA (Normalization qPCR Array, where
      qPCR is quantitative real-time polymerase chain reaction) suitable for the
      identification of a set of microRNAs (miRNAs) to be used for data normalization
      in view of subsequent validation studies with qPCR data. NqA is available through
      the website of the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan
      (http://www.istitutotumori.mi.it/modules.php?name=Content&pa=showpage&pid=812)
      with a dedicated user's guide. We applied our function on a qPCR dataset
      downloaded from the Gene Expression Omnibus (GEO) database. Results show that NqA
      provides a functional subset of reference miRNAs and a set of promising
      significantly modulated miRNAs for subsequent validation studies. 

PMID- 24892987
TI  - An advanced glycation end product (AGE)-rich diet promotes Nepsilon-carboxymethyl
      lysine accumulation in the cardiac tissue and tendons of rats.
AB  - The purpose of this study was to investigate the intake, excretion, and tissue
      accumulation of carboxymethyl-lysine (CML), after feeding rats a diet containing
      advanced glycation end products (AGEs) from a glucose-lysine (GL) model system.
      Rats were distributed into two groups and assigned to a control diet or a diet
      including 3% heated GL (GL diet) for three months. Feces and urine were collected
      over the last week. After sacrifice, serum was obtained and some organs were
      removed for CML analysis. The percentage of fecal CML was 2.5-fold higher in the
      animals fed the GL diet (33.2 vs 76.5% for control and GL group), whereby total
      recovery was 91.8% compared with a level of 54.6% in the animals fed the control
      chow, evidencing the importance of the chemical form and the net quantity of
      dietary CML on its elimination. We suggest that dietary dicarbonyl compounds from
      GL diet or dietary CML itself are responsible for CML accumulation in hearts and
      tendons. The most significant result of the present study is that the regular
      consumption of dietary AGEs in healthy individuals promotes CML accumulation in
      some organs. 

PMID- 24892986
TI  - Detection of cresyl phosphate-modified butyrylcholinesterase in human plasma for
      chemical exposure associated with aerotoxic syndrome.
AB  - Flight crews complain of illness following a fume event in aircraft. A chemical
      in jet engine oil, the neurotoxicant tri-o-cresyl phosphate, after metabolic
      activation to cresyl saligenin phosphate makes a covalent adduct on
      butyrylcholinesterase (BChE). We developed a mass spectrometry method for
      detection of the cresyl phosphate adduct on human BChE as an indicator of
      exposure. Monoclonal mAb2, whose amino acid sequence is provided, was crosslinked
      to cyanogen bromide-activated Sepharose 4B and used to immunopurify plasma BChE
      treated with cresyl saligenin phosphate. BChE was released with acetic acid,
      digested with pepsin, and analyzed by liquid chromatography-tandem mass
      spectrometry (LC-MSMS) on the Triple TOF 5600 mass spectrometer. Peptide
      FGES198AGAAS with an added mass of 170 Da from cresyl phosphate on serine 198
      (Ser198) was detected as parent ion 966.4 Da. When characteristic daughter ions
      were monitored in the MSMS spectrum, the limit of detection was 0.1% cresyl
      saligenin phosphate inhibited plasma BChE. This corresponds to 2*10(-9) g in 0.5
      ml or 23*10(-15) moles of inhibited BChE in 0.5 ml of plasma. In conclusion, a
      sensitive assay for exposure to tri-o-cresyl phosphate was developed.
      Laboratories that plan to use this method are cautioned that a positive result
      gives no proof that tri-o-cresyl phosphate is toxic at low levels.

PMID- 24892988
TI  - Liver sinusoidal endothelial cells promote lymphohematopoietic differentiation
      from murine embryonic stem cells: role of soluble factors.
AB  - Liver sinusoid endothelial cells (LSEC) constitute an in vitro and in vivo
      microenvironment for the proliferation and differentiation of hematopoietic stem
      cells (HSC). Previously, we have shown that LSEC support the survival and growth
      of murine embryonic stem cells (ESC). In this study, we investigated the capacity
      of LSEC to promote hematopoietic differentiation from the murine ESC cell line,
      CGR8. Undifferentiated ESC were cultured on LSEC monolayers in the absence of
      exogenous cytokines. After 10 and 20 days, cells were harvested and examined by
      their morphology, phenotype and capacity of hematopoietic colony formation.
      Microscopic observation of LSEC/ESC cocultures showed the presence of cobblestone
      areas formation, which indicates active hematopoiesis. Morphological analysis of
      cell from these foci showed the presence of hematopoietic cells at different
      stages of differentiation. Cells expressing B lymphoid markers (B220 and CD19)
      were detected by flow cytometry, and clonogenic assays showed the formation of
      CFU-pre B colonies. Similar results were observed when ESC were cultured with
      LSEC conditioned media. Myeloid precursors were also detected by the presence of
      CFU-GM colonies and cells expressing myeloid markers. These results indicate that
      LSEC provided an in vitro microenvironment mainly for B cell development, but
      also myeloid differentiation from ESC. Coculture of ESC with LSEC may constitute
      a very powerful tool to study the mechanisms involved in B cell generation from
      ESC. 

PMID- 24892989
TI  - Activation of liver X receptor enhances the proliferation and migration of
      endothelial progenitor cells and promotes vascular repair through PI3K/Akt/eNOS
      signaling pathway activation.
AB  - Vascular endothelial injury is a major cause of many cardiovascular diseases. The
      proliferation and migration of endothelial progenitor cells (EPCs) play a pivotal
      role in endothelial regeneration and repair after vascular injury. Recently,
      liver X receptor (LXR) activation has been suggested as a potential target for
      novel therapeutic interventions in the treatment of cardiovascular disease.
      However, the effects of LXR activation on endothelial regeneration and repair, as
      well as EPC function, have not been investigated. In the present study, we
      demonstrate that LXRs, including LXRalpha and LXRbeta, are expressed and
      functional in rat bone marrow-derived EPCs. Treatment with an LXR agonist,
      TO901317 (TO) or GW3965 (GW), significantly increased the proliferation and
      migration of EPCs, as well as Akt and eNOS phosphorylation in EPCs. Moreover, LXR
      agonist treatment enhanced the expression and secretion of vascular endothelial
      growth factor in EPCs. LXR agonists accelerated re-endothelialization in injured
      mouse carotid arteries in vivo. These data confirm that LXR activation may
      improve EPC function and endothelial regeneration and repair after vascular
      injury by activating the PI3K/Akt/eNOS pathway. We conclude that LXRs may be
      attractive targets for drug development in the treatment of cardiovascular
      diseases associated with vascular injury. 

PMID- 24892990
TI  - Nodules in autoimmune thyroiditis are associated with increased risk of thyroid
      cancer in surgical series but not in cytological series: evidence for selection
      bias.
AB  - BACKGROUND: The association of thyroid cancer and autoimmune thyroiditis (AIT)
      has been widely addressed, with conflicting results in surgical and cytological
      series, likely affected by selection bias. OBJECTIVE: The objective of the study
      was to evaluate the association between the cytological features suggestive or
      indicative of malignancy and AIT in 2504 consecutive patients (2029 females and
      475 males, mean age 58.3 +/- 14.1 y) undergoing fine-needle aspiration cytology
      for thyroid nodules. PATIENTS: Based on the clinical diagnosis, patients were
      divided into four groups: AIT with nodules (N-AIT, 14.9%); nodular Graves disease
      (N-GD, 2.8%); nodular goiter and negative thyroid antibodies (NGAb-, 68.4%); and
      nodular goiter with positive thyroid antibodies (NGAb+, 13.9%). RESULTS: The
      prevalence of patients with cytological features suggestive (Thy4) or indicative
      of malignancy (Thy5) was 4.5 % in the N-AIT group, not different compared with
      the other groups (N-GD, 5.6%; NGAb-, 5.0%; NGAb+, 4.3%). No difference was also
      found in the other categories (Thy2 and Thy3). When the same analysis was
      performed in the subgroup of patients (14.3%) with a histological confirmation,
      we found that the prevalence of differentiated thyroid cancer was significantly
      higher (P = .01) in the N-AIT group (67.8%) compared with the other groups (N-GD,
      40.0%; NGAb-, 37.2%; NGAb+, 36.9%). CONCLUSIONS: The results of our cytological
      series do not support a link between N-AIT and thyroid cancer. The association
      between cancer and N-AIT found in the histology-based series is likely due to a
      selection bias represented by the fact that the prevalent indication for surgery
      in the N-AIT group was suspicious cytology (60.7% of patients) more frequently
      than in the other groups.

PMID- 24892992
TI  - Biochemical characterization of the phosphatase domain of the tumor suppressor PH
      domain leucine-rich repeat protein phosphatase.
AB  - PH domain leucine-rich repeat protein phosphatase (PHLPP) directly
      dephosphorylates and inactivates Akt and protein kinase C and is therefore a
      prime target for pharmacological intervention of two key signaling pathways, the
      phosphatidylinositol 3-kinase and diacylglycerol signaling pathways. Here we
      report on the first biochemical characterization of the phosphatase domain of a
      PHLPP family member. The human PHLPP1 and PHLPP2 phosphatase domains were
      expressed and purified from bacteria or insect cells and their activities
      compared to that of full-length proteins immunoprecipitated from mammalian cells.
      Biochemical analyses reveal that the PHLPP phosphatase domain effectively
      dephosphorylates synthetic and peptidic substrates, that its activity is
      modulated by metals and lipophilic compounds, and that it has relatively high
      thermal stability. Mutational analysis of PHLPP2 reveals an unusual active site
      architecture compared to the canonical architecture of PP2C phosphatases and
      identifies key acidic residues (Asp 806, Glu 989, and Asp 1024) and bulky
      aromatic residues (Phe 783 and Phe 808) whose mutation impairs activity.
      Consistent with a unique active site architecture, we identify inhibitors that
      discriminate between PHLPP2 and PP2Calpha. These data establish PHLPP as a member
      of the PP2C family of phosphatases with a unique active site architecture. 

PMID- 24892993
TI  - Prediction of glaucomatous visual field progression: pointwise analysis.
AB  - PURPOSE: To evaluate whether pointwise regression analysis of serial measures of
      retinal sensitivity can predict future visual field (VF) loss. METHODS: Medical
      records of 158 patients with glaucomatous eyes with at least 6 years follow-up
      and 10 reliable VF exams were retrospectively analyzed. The entire follow-up
      period was divided into two, roughly corresponding to the first (early period)
      and second (late period) half of follow-up. Retinal sensitivity data obtained
      from the Swedish interactive threshold algorithm standard or full-threshold VF
      tests were analyzed, and linear and first-order exponential regression analyses
      of retinal sensitivity against time were performed to obtain the slope of
      regression analysis in each VF test location. Paired t tests were used to compare
      the slopes of the early and late period in each regression analysis. RESULTS:
      When assessed by linear regression analysis, inferior nasal location showed
      highest rate of change (-0.52 dB/year) in early period. Late period showed
      generally faster rate of progression compared to early period. Superior arcuate
      and superior and inferior nasal locations showed that early and late slopes did
      not show significant difference (p value, 0.19 ~ 0.49). Central and edged
      locations showed significant difference between the two slopes (p value  < 0.05).
      First-order exponential regression analysis showed similar result. DISCUSSION:
      Superior arcuate and superior and inferior nasal areas in VF had a consistent
      rate of change of retinal sensitivity, indicating that these locations may have
      the higher capability for prediction of future deterioration. These results
      suggest that location should be considered when predicting glaucomatous VF
      progression.

PMID- 24892991
TI  - Vitamin D and endothelial vasodilation in older individuals: data from the PIVUS
      study.
AB  - CONTEXT: Vitamin D plays a role in a wide range of extraskeletal processes,
      including vascular function. Endothelial dysfunction is a predictor of
      cardiovascular disease, especially in older subjects. However, the relationship
      between vitamin D levels and indexes of endothelial vasodilation has never been
      fully addressed in older individuals. OBJECTIVE: The objective of this study was
      to examine the association between vitamin D and endothelial function in a large
      community-based sample of older subjects. METHODS: This cross-sectional study
      involved 852 community-dwelling men and women aged 70 years from the Prospective
      Study of the Vasculature in Uppsala Seniors (PIVUS), with complete data on
      vascular function and 25-hydroxyvitamin D. We evaluated endothelium-dependent
      vasodilation by an invasive forearm technique with acetylcholine, endothelium
      independent vasodilation by sodium nitroprussiate, flow-mediated vasodilation,
      and the pulse wave analysis (reflectance index). Vitamin D levels were measured
      by chemiluminescence. We used multivariate regression models adjusted for body
      mass index (model 1) and for multiple confounders (high-sensitivity C-reactive
      protein, insulin, total cholesterol, high-density lipoprotein-cholesterol, low
      density lipoprotein-cholesterol, smoking, sex hormones, season of blood
      collection, hypertension, diabetes, cardiovascular medications and diseases,
      statin usage, plasma calcium and calcium intake, PTH, physical exercise, liver
      and kidney function tests, albumin; model 2). RESULTS: In women, but not in men,
      vitamin D levels were positively associated with endothelium-independent
      vasodilation in both model 1 (beta +/- SE = 1.41 +/- 0.54; P = .001), and model 2
      (beta +/- SE = 2.01 +/- 0.68; P = .003).We found no significant relationship
      between vitamin D levels and endothelium-dependent vasodilation, flow-mediated
      vasodilation, and reflectance index in both sexes. CONCLUSIONS: In older women,
      but not in men, vitamin D is positively and independently associated with EIDV.

PMID- 24892996
TI  - Cancer immunotherapeutics: evolution of monoclonal antibodies to peptide
      immunogens.
AB  - The Wistar Institute under Hilary Koprowski's direction played a preeminent role
      in bringing the fruits of basic science to clinic through biotechnology and life
      science enterprises. Koprowski's early view on the utility of monoclonal
      antibodies has been validated to some extent, because monoclonal therapeutics
      form one of the fastest growing and most successful and lucrative segments within
      the biopharmaceutical sector. Over 30 monoclonal antibody drugs have now been
      approved in the United States and Europe. However, monoclonal antibodies might be
      viewed in the context of a bridge to the future for vaccines. The Wistar
      Institute's reputation, while built on vaccines for infectious diseases, can be
      translated in years to come into vaccines for cancer.

PMID- 24892994
TI  - Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax.
AB  - The blind mole rat (BMR), Spalax galili, is an excellent model for studying
      mammalian adaptation to life underground and medical applications. The BMR spends
      its entire life underground, protecting itself from predators and climatic
      fluctuations while challenging it with multiple stressors such as darkness,
      hypoxia, hypercapnia, energetics and high pathonecity. Here we sequence and
      analyse the BMR genome and transcriptome, highlighting the possible genomic
      adaptive responses to the underground stressors. Our results show high rates of
      RNA/DNA editing, reduced chromosome rearrangements, an over-representation of
      short interspersed elements (SINEs) probably linked to hypoxia tolerance,
      degeneration of vision and progression of photoperiodic perception, tolerance to
      hypercapnia and hypoxia and resistance to cancer. The remarkable traits of the
      BMR, together with its genomic and transcriptomic information, enhance our
      understanding of adaptation to extreme environments and will enable the
      utilization of BMR models for biomedical research in the fight against cancer,
      stroke and cardiovascular diseases. 

PMID- 24892995
TI  - Nitrosative stress and nitrated proteins in trichloroethene-mediated
      autoimmunity.
AB  - Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has
      been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma
      and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely
      unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the
      contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N
      acetylcysteine (NAC) supplementation provided protection by attenuating oxidative
      stress. This study was undertaken to further evaluate the contribution of
      nitrosative stress in TCE-mediated autoimmunity and to identify proteins
      susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE,
      NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ~ 250
      mg/kg/day via drinking water). TCE exposure led to significant increases in serum
      anti-nuclear and anti-histone antibodies together with significant induction of
      iNOS and increased formation of nitrotyrosine (NT) in sera and livers. Proteomic
      analysis identified 14 additional nitrated proteins in the livers of TCE-treated
      mice. Furthermore, TCE exposure led to decreased GSH levels and increased
      activation of NF-kappaB. Remarkably, NAC supplementation not only ameliorated TCE
      induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins,
      NF-kappaB p65 activation and increased GSH levels, but also the markers of
      autoimmunity, as evident from decreased levels of autoantibodies in the sera.
      These findings provide support to the role of nitrosative stress in TCE-mediated
      autoimmune response and identify specific nitrated proteins which could have
      autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC
      provides an approach for designing therapeutic strategies.

PMID- 24893001
TI  - Stochasticity and determinism: how density-independent and density-dependent
      processes affect population variability.
AB  - A persistent debate in population ecology concerns the relative importance of
      environmental stochasticity and density dependence in determining variability in
      adult year-class strength, which contributes to future reproduction as well as
      potential yield in exploited populations. Apart from the strength of the
      processes, the timing of density regulation may affect how stochastic variation,
      for instance through climate, translates into changes in adult abundance. In this
      study, we develop a life-cycle model for the population dynamics of a large
      marine fish population, Northeast Arctic cod, to disentangle the effects of
      density-independent and density-dependent processes on early life-stages, and to
      quantify the strength of compensatory density dependence in the population. The
      model incorporates information from scientific surveys and commercial harvest,
      and dynamically links multiple effects of intrinsic and extrinsic factors on all
      life-stages, from eggs to spawners. Using a state-space approach we account for
      observation error and stochasticity in the population dynamics. Our findings
      highlight the importance of density-dependent survival in juveniles, indicating
      that this period of the life cycle largely determines the compensatory capacity
      of the population. Density regulation at the juvenile life-stage dampens the
      impact of stochastic processes operating earlier in life such as environmental
      impacts on the production of eggs and climate-dependent survival of larvae. The
      timing of stochastic versus regulatory processes thus plays a crucial role in
      determining variability in adult abundance. Quantifying the contribution of
      environmental stochasticity and compensatory mechanisms in determining population
      abundance is essential for assessing population responses to climate change and
      exploitation by humans.

PMID- 24893002
TI  - Estimating the temporal domain when the discount of the net evaporation term
      affects the resulting net precipitation pattern in the moisture budget using a 3
      D Lagrangian approach.
AB  - The Lagrangian FLEXPART model has been used during the last decade to detect
      moisture sources that affect the climate in different regions of the world. While
      most of these studies provided a climatological perspective on the atmospheric
      branch of the hydrological cycle in terms of precipitation, none assessed the
      minimum temporal domain for which the climatological approach is valid. The
      methodology identifies the contribution of humidity to the moisture budget in a
      region by computing the changes in specific humidity along backward (or forward)
      trajectories of air masses over a period of ten days beforehand (afterwards),
      thereby allowing the calculation of monthly, seasonal and annual averages. The
      current study calculates as an example the climatological seasonal mean and
      variance of the net precipitation for regions in which precipitation exceeds
      evaporation (E-P<0) for the North Atlantic moisture source region using different
      time periods, for winter and summer from 1980 to 2000. The results show that net
      evaporation (E-P>0) can be discounted after when the integration of E-P is done
      without affecting the general net precipitation patterns when it is discounted in
      a monthly or longer time scale. 

PMID- 24893000
TI  - Application of a new hybrid model with seasonal auto-regressive integrated moving
      average (ARIMA) and nonlinear auto-regressive neural network (NARNN) in
      forecasting incidence cases of HFMD in Shenzhen, China.
AB  - BACKGROUND: Outbreaks of hand-foot-mouth disease (HFMD) have been reported for
      many times in Asia during the last decades. This emerging disease has drawn
      worldwide attention and vigilance. Nowadays, the prevention and control of HFMD
      has become an imperative issue in China. Early detection and response will be
      helpful before it happening, using modern information technology during the
      epidemic. METHOD: In this paper, a hybrid model combining seasonal auto
      regressive integrated moving average (ARIMA) model and nonlinear auto-regressive
      neural network (NARNN) is proposed to predict the expected incidence cases from
      December 2012 to May 2013, using the retrospective observations obtained from
      China Information System for Disease Control and Prevention from January 2008 to
      November 2012. RESULTS: The best-fitted hybrid model was combined with seasonal
      ARIMA [Formula: see text] and NARNN with 15 hidden units and 5 delays. The hybrid
      model makes the good forecasting performance and estimates the expected incidence
      cases from December 2012 to May 2013, which are respectively -965.03, -1879.58,
      4138.26, 1858.17, 4061.86 and 6163.16 with an obviously increasing trend.
      CONCLUSION: The model proposed in this paper can predict the incidence trend of
      HFMD effectively, which could be helpful to policy makers. The usefulness of
      expected cases of HFMD perform not only in detecting outbreaks or providing
      probability statements, but also in providing decision makers with a probable
      trend of the variability of future observations that contains both historical and
      recent information.

PMID- 24893003
TI  - Phage neutralization by sera of patients receiving phage therapy.
AB  - The aim of our investigation was to verify whether phage therapy (PT) can induce
      antiphage antibodies. The antiphage activity was determined in sera from 122
      patients from the Phage Therapy Unit in Wroclaw with bacterial infections before
      and during PT, and in sera from 30 healthy volunteers using a neutralization
      test. Furthermore, levels of antiphage antibodies were investigated in sera of 19
      patients receiving staphylococcal phages and sera of 20 healthy volunteers using
      enzyme-linked immunosorbent assay. The phages were administered orally, locally,
      orally/locally, intrarectally, or orally/intrarectally. The rate of phage
      inactivation (K) estimated the level of phages' neutralization by human sera. Low
      K rates were found in sera of healthy volunteers (K <= 1.73). Low K rates were
      detected before PT (K <= 1.64). High antiphage activity of sera K > 18 was
      observed in 12.3% of examined patients (n = 15) treated with phages locally (n =
      13) or locally/orally (n = 2) from 15 to 60 days of PT. High K rates were found
      in patients treated with some Staphylococcus aureus, Pseudomonas aeruginosa, and
      Enterococcus faecalis phages. Low K rates were observed during PT in sera of
      patients using phages orally (K <= 1.04). Increased inactivation of phages by
      sera of patients receiving PT decreased after therapy. These results suggest that
      the antiphage activity in patients' sera depends on the route of phage
      administration and phage type. The induction of antiphage activity of sera during
      or after PT does not exclude a favorable result of PT.

PMID- 24893004
TI  - Perioperative complications of total en bloc spondylectomy: adverse effects of
      preoperative irradiation.
AB  - BACKGROUND: Total en bloc spondylectomy (TES) is associated with a high
      complication rate because it is technically demanding and involves patients
      compromised by cancer. Specifically, perioperative complications are more likely
      to occur in patients receiving preoperative irradiation. We examined the
      perioperative complications associated with TES in patients receiving
      preoperative irradiation. METHODS: Seventy-seven patients underwent TES between
      May 2010 and April 2013. We performed a retrospective review of prospectively
      collected data for 50 patients with metastatic tumors of the thoracic spine,
      excluding patients with primary spinal tumors, lumbar spinal metastasis, and
      combined anterior and posterior approach TES. Patients were divided into 2
      groups: those with preoperative irradiation (RT-TES group, 18 patients) and those
      without preoperative irradiation (TES group, 32 patients). The following
      perioperative complications, occurring within 2 months of surgery, were compared
      between the groups: intraoperative dural injuries, epidural hematomas, deep
      surgical-site infections, postoperative cerebrospinal fluid leakage, wound
      dehiscence, pleural effusions, and neurological deficits. RESULTS: Significant
      differences in patient characteristics were not observed between the RT-TES and
      TES groups. Perioperative TES complications occurred in 20/50 patients (40.0%).
      The complication rate in the RT-TES group was 77.8% (14 out of 18), threefold
      higher than the 18.8% (6 out of 32) in the TES group (P<0.01). The incidence of
      complications, including intraoperative dural injuries, postoperative
      cerebrospinal fluid leakage, wound dehiscence, and pleural effusions, was
      significantly higher in the RT-TES group (P<0.01). CONCLUSION: The perioperative
      complication rate associated with TES for spinal metastasis was significantly
      higher among patients receiving preoperative irradiation than among those not
      receiving preoperative irradiation.

PMID- 24893005
TI  - A major locus for chloride accumulation on chromosome 5A in bread wheat.
AB  - Chloride (Cl-) is an essential micronutrient for plant growth, but can be toxic
      at high concentrations resulting in reduced growth and yield. Although saline
      soils are generally dominated by both sodium (Na+) and Cl- ions, compared to Na+
      toxicity, very little is known about physiological and genetic control mechanisms
      of tolerance to Cl- toxicity. In hydroponics and field studies, a bread wheat
      mapping population was tested to examine the relationships between physiological
      traits [Na+, potassium (K+) and Cl- concentration] involved in salinity tolerance
      (ST) and seedling growth or grain yield, and to elucidate the genetic control
      mechanism of plant Cl- accumulation using a quantitative trait loci (QTL)
      analysis approach. Plant Na+ or Cl- concentration were moderately correlated
      (genetically) with seedling biomass in hydroponics, but showed no correlations
      with grain yield in the field, indicating little value in selecting for ion
      concentration to improve ST. In accordance with phenotypic responses, QTL
      controlling Cl- accumulation differed entirely between hydroponics and field
      locations, and few were detected in two or more environments, demonstrating
      substantial QTL-by-environment interactions. The presence of several QTL for Cl-
      concentration indicated that uptake and accumulation was a polygenic trait. A
      major Cl- concentration QTL (5A; barc56/gwm186) was identified in three field
      environments, and accounted for 27-32% of the total genetic variance. Alignment
      between the 5A QTL interval and its corresponding physical genome regions in
      wheat and other grasses has enabled the search for candidate genes involved in Cl
      transport, which is discussed. 

PMID- 24893006
TI  - An individual-based model of transmission of resistant bacteria in a veterinary
      teaching hospital.
AB  - Veterinary nosocomial infections caused by antibiotic resistant bacteria cause
      increased morbidity, higher cost and length of treatment and increased zoonotic
      risk because of the difficulty in treating them. In this study, an individual
      based model was developed to investigate the effects of movements of canine
      patients among ten areas (transmission points) within a veterinary teaching
      hospital, and the effects of these movements on transmission of antibiotic
      susceptible and resistant pathogens. The model simulates contamination of
      transmission points, healthcare workers, and patients as well as the effects of
      decontamination of transmission points, disinfection of healthcare workers, and
      antibiotic treatments of canine patients. The model was parameterized using data
      obtained from hospital records, information obtained by interviews with hospital
      staff, and the published literature. The model suggested that transmission
      resulting from contact with healthcare workers was common, and that certain
      transmission points (housing wards, diagnostics room, and the intensive care
      unit) presented higher risk for transmission than others (lobby and surgery).
      Sensitivity analyses using a range of parameter values demonstrated that the risk
      of acquisition of colonization by resistant pathogens decreased with shorter
      patient hospital stays (P<0.0001), more frequent decontamination of transmission
      points and disinfection of healthcare workers (P<0.0001) and better compliance of
      healthcare workers with hygiene practices (P<0.0001). More frequent
      decontamination of heavily trafficked transmission points was especially
      effective at reducing transmission of the model pathogen. 

PMID- 24893008
TI  - Nucleobase-functionalized conjugated polymer for detection of copper(II).
AB  - In recent years, supramolecular organization of thiophene derivatives, oligo- and
      polythiophene, have been developed with various designs to achieve complex
      functions. Here, we describe the synthesis and characterization of a conjugated
      polymer with thymidine side chain bases and polythiophene backbones (PTT) instead
      of phosphate bonds in DNA, and the PTT exhibits exceptional fluorescence
      quenching efficiency upon binding of Cu(2+) ions in aqueous medium, which is
      suggested to be electron transfer from the pi* orbit at the excited state of PTT
      to the 3d orbit of Cu(2+) ions and subsequent Cu(2+)-mediated interpolymer pi
      stacking aggregation. Furthermore, Cu(2+) ions can be selectively and easily
      monitored by the fluorescence quenching of PTT, which can be used for detection
      of Cu(2+) ions with good selectivity and high sensitivity in aqueous medium. Both
      experimental and theoretical methods have been devoted to demonstrate the strong
      affinity and steric interaction of PTT toward Cu(2+). These findings will
      illustrate new directions for the design of nucleobase-functionalized materials
      with transition metals responsive activity. 

PMID- 24893007
TI  - A proteolytic cascade controls lysosome rupture and necrotic cell death mediated
      by lysosome-destabilizing adjuvants.
AB  - Recent studies have linked necrotic cell death and proteolysis of inflammatory
      proteins to the adaptive immune response mediated by the lysosome-destabilizing
      adjuvants, alum and Leu-Leu-OMe (LLOMe). However, the mechanism by which lysosome
      destabilizing agents trigger necrosis and proteolysis of inflammatory proteins is
      poorly understood. The proteasome is a cellular complex that has been shown to
      regulate both necrotic cell death and proteolysis of inflammatory proteins. We
      found that the peptide aldehyde proteasome inhibitors, MG115 and MG132, block
      lysosome rupture, degradation of inflammatory proteins and necrotic cell death
      mediated by the lysosome-destabilizing peptide LLOMe. However, non-aldehyde
      proteasome inhibitors failed to prevent LLOMe-induced cell death suggesting that
      aldehyde proteasome inhibitors triggered a pleotropic effect. We have previously
      shown that cathepsin C controls lysosome rupture, necrotic cell death and the
      adaptive immune response mediated by LLOMe. Using recombinant cathepsin C, we
      found that aldehyde proteasome inhibitors directly block cathepsin C, which
      presumably prevents LLOMe toxicity. The cathepsin B inhibitor CA-074-Me also
      blocks lysosome rupture and necrotic cell death mediated by a wide range of
      necrosis inducers, including LLOMe. Using cathepsin-deficient cells and
      recombinant cathepsins, we demonstrate that the cathepsins B and C are not
      required for the CA-074-Me block of necrotic cell death. Taken together, our
      findings demonstrate that lysosome-destabilizing adjuvants trigger an early
      proteolytic cascade, involving cathepsin C and a CA-074-Me-dependent protease.
      Identification of these early events leading to lysosome rupture will be crucial
      in our understanding of processes controlling necrotic cell death and immune
      responses mediated by lysosome-destabilizing adjuvants. 

PMID- 24893009
TI  - Paraphyly of the subgenus Sintonius (Diptera, Psychodidae, Sergentomyia): status
      of the Malagasy species. Creation of a new subgenus and description of a new
      species.
AB  - During an inventory of Phlebotomine sand flies carried out in Madagascar, we have
      identified some specimens showing morphological characters related to the
      subgenus Sintonius of the genus Sergentomyia. We started a molecular study based
      on cytochrome b mtDNA and on D1-D2 and D8 domains of the rDNA. The sampling
      includes all the Sergentomyia species available and also S. (Sergentomyia)
      schwetzi, S. (Parrotomyia) magna, and the following species belonging to the
      subgenus Sintonius: S. clydei, S. christophersi, S. affinis vorax, S. adleri and
      S. meilloni. The Sintonius subgenus (sensu Theodor) is paraphyletic. The Malagasy
      specimens morphologically Sintonius-like are never clustered with the continental
      Sintonius. We propose a new subgenus to include them: Trouilletomyia subg. nov.
      Due to the lack of mesanepisternal setae, the species huberti is removed from the
      genus Phlebotomus and we propose here a new combination: Sergentomyia huberti
      comb. nov. The male of S. huberti is pinpointed and described for the first time.
      Lastly, a new species for Science is described on one female: Sergentomyia
      (Trouilletomyia) boironis n. sp. 

PMID- 24893010
TI  - Impact of climate change and man-made irrigation systems on the transmission
      risk, long-term trend and seasonality of human and animal fascioliasis in
      Pakistan.
AB  - Large areas of the province of Punjab, Pakistan are endemic for fascioliasis,
      resulting in high economic losses due to livestock infection but also affecting
      humans directly. The prevalence in livestock varies pronouncedly in space and
      time (1-70%). Climatic factors influencing fascioliasis presence and potential
      spread were analysed based on data from five meteorological stations during 1990
      2010. Variables such as wet days (Mt), water-budget-based system (Wb-bs) indices
      and the normalized difference vegetation index (NDVI), were obtained and
      correlated with geographical distribution, seasonality patterns and the two
      decade evolution of fascioliasis in livestock throughout the province. The
      combined approach by these three indices proved to furnish a useful tool to
      analyse the complex epidemiology that includes (i) sheep-goats and
      cattlebuffaloes presenting different immunological responses to fasciolids; (ii)
      overlap of Fasciola hepatica and F. gigantica; (iii) co-existence of highlands
      and lowlands in the area studied; and (iv) disease transmission following bi
      seasonality with one peak related to natural rainfall and another peak related to
      man-made irrigation. Results suggest a human infection situation of concern and
      illustrate how climate and anthropogenic environment modifications influence both
      geographical distribution and seasonality of fascioliasis risks. Increased
      fascioliasis risk throughout the Punjab plain and its decrease in the northern
      highlands of the province became evident during the study period. The high risk
      in the lowlands is worrying given that Punjab province largely consists of low
      altitude, highly irrigated plains. The importance of livestock in this province
      makes it essential to prioritise adequate control measures. An annual treatment
      scheme to control the disease is recommended to be applied throughout the whole
      province. 

PMID- 24893011
TI  - Modelling spatial distribution of snails transmitting parasitic worms with
      importance to human and animal health and analysis of distributional changes in
      relation to climate.
AB  - The environment, the on-going global climate change and the ecology of animal
      species determine the localisation of habitats and the geographical distribution
      of the various species in nature. The aim of this study was to explore the
      effects of such changes on snail species not only of interest to naturalists but
      also of importance to human and animal health. The spatial distribution of
      freshwater snail intermediate hosts involved in the transmission of
      schistosomiasis, fascioliasis and paramphistomiasis (i.e. Bulinus globosus,
      Biomphalaria pfeifferi and Lymnaea natalensis) were modelled by the use of a
      maximum entropy algorithm (Maxent). Two snail observation datasets from Zimbabwe,
      from 1988 and 2012, were compared in terms of geospatial distribution and
      potential distributional change over this 24-year period investigated. Climate
      data, from the two years were identified and used in a species distribution
      modelling framework to produce maps of predicted suitable snail habitats. Having
      both climate- and snail observation data spaced 24 years in time represent a
      unique opportunity to evaluate biological response of snails to changes in
      climate variables. The study shows that snail habitat suitability is highly
      variable in Zimbabwe with foci mainly in the central Highveld but also in areas
      to the South and West. It is further demonstrated that the spatial distribution
      of suitable habitats changes with variation in the climatic conditions, and that
      this parallels that of the predicted climate change. 

PMID- 24893012
TI  - Study of the snail intermediate hosts for Schistosoma mansoni on Itamaraca Island
      in northeast Brazil: spatial displacement of Biomphalaria glabrata by
      Biomphalaria straminea.
AB  - In 2012 a malacological survey of the breeding sites of Biomphalaria glabrata and
      B. straminea , the two intermediate host snails of Schistosoma mansoni , was
      carried out on Itamaraca Island in Pernambuco, Brazil. This study has now been
      extended by studying the competition between the two species. Snails were
      collected and dissected to identify the species and tests were performed to
      verify S. mansoni infection. Student's t test was used to compare the proportion
      between the two species and their breeding sites and a parasitological survey was
      conducted among local residents, using the Kato-Katz method. The spatial
      distribution of the two snail species was determined using TerraView, while a
      snail density map was constructed by Kernel estimate. The survey identified two
      breeding sites for B. glabrata with 17 specimens and 19 breeding sites for B.
      straminea with 459 snails, all of them negative for S. mansoni infection. The
      statistical analysis revealed that the proportion of the numbers of specimens and
      breeding sites of B. straminea (37.84 +/- 9.01) were significantly greater than
      those of B. glabrata (8.50 +/- 6.50). Parasitological examinations from 41
      residents diagnosed two cases of schistosomiasis with parasite loads of 60 and 84
      eggs per 1 g of stool, respectively. This indiction of a competitive process
      between the two snail species requires monitoring of schistosomiasis in the
      resident and travelling human populations occupying this environment, which could
      potentially result in social and economic changes on the island risking its
      attraction as a centre for eco-tourism. 

PMID- 24893013
TI  - Study of the variation of schistosomiasis risk in Lake Poyang in the People's
      Republic of China using multiple space-borne sensors for the monitoring and
      modelling.
AB  - The dynamics of the Poyang Lake in Jiangxi province, People's Republic of China
      has been monitored to demonstrate the association of various variables with the
      distribution of schistosomiasis transmission with particular reference to the
      annual variation of the habitats for the Oncomelania snail, the intermediate host
      of Schistosoma japonicum. This was studied with multiple space-borne sensors,
      including the ENVISAT radar altimeter (RA-2) and MODIS/Terra radiometry data
      products such as the 16-day enhanced vegetation index, the 8-day sun reflectance,
      and the derived modified normalized difference water index. The measurements of
      physical properties were in good accordance with previous reports based on in
      situ gauge data, spectroradiometry and other optical methods, which encouraged us
      to build a predictive model based on reported geospatial constraints to assess
      the limits of potential variation of the snail habitat areas. The simulated
      results correspond fairly well with surveys conducted by local authorities
      showing a correlation coefficient of 0.82 between highpotential habitat areas and
      local estimates in a 9-year (2002-2010) analysis. Taken together, these data
      indicate that spaceborne observations and in situ measurements can be integrated
      and used as a first step of a monitoring system for control and analysis of the
      potential of schistosomiasis dissemination. Since the true range and intensity of
      transmission in the study region remain elusive at present, a long-term survey
      around the lake is warranted to build a robust, parametric model. 

PMID- 24893014
TI  - Mapping and modelling the geographical distribution of soil-transmitted
      helminthiases in Peninsular Malaysia: implications for control approaches.
AB  - Soil-transmitted helminth (STH) infections in Malaysia are still highly
      prevalent, especially in rural and remote communities. Complete estimations of
      the total disease burden in the country has not been performed, since available
      data are not easily accessible in the public domain. The current study utilised
      geographical information system (GIS) to collate and map the distribution of STH
      infections from available empirical survey data in Peninsular Malaysia,
      highlighting areas where information is lacking. The assembled database,
      comprising surveys conducted between 1970 and 2012 in 99 different locations,
      represents one of the most comprehensive compilations of STH infections in the
      country. It was found that the geographical distribution of STH varies
      considerably with no clear pattern across the surveyed locations. Our attempt to
      generate predictive risk maps of STH infections on the basis of ecological limits
      such as climate and other environmental factors shows that the prevalence of
      Ascaris lumbricoides is low along the western coast and the southern part of the
      country, whilst the prevalence is high in the central plains and in the North. In
      the present study, we demonstrate that GIS can play an important role in
      providing data for the implementation of sustainable and effective STH control
      programmes to policy-makers and authorities in charge. 

PMID- 24893015
TI  - Risk map for cutaneous leishmaniasis in Ethiopia based on environmental factors
      as revealed by geographical information systems and statistics.
AB  - Cutaneous leishmaniasis (CL) is a neglected tropical disease strongly associated
      with poverty. Treatment is problematic and no vaccine is available. Ethiopia has
      seen new outbreaks in areas previously not known to be endemic, often with co
      infection by the human immunodeficiency virus (HIV) with rates reaching 5.6% of
      the cases. The present study concerns the development of a risk model based on
      environmental factors using geographical information systems (GIS), statistical
      analysis and modelling. Odds ratio (OR) of bivariate and multivariate logistic
      regression was used to evaluate the relative importance of environmental factors,
      accepting P <= 0.056 as the inclusion level for the model's environmental
      variables. When estimating risk from the viewpoint of geographical surface,
      slope, elevation and annual rainfall were found to be good predictors of CL
      presence based on both probabilistic and weighted overlay approaches. However,
      when considering Ethiopia as whole, a minor difference was observed between the
      two methods with the probabilistic technique giving a 22.5% estimate, while that
      of weighted overlay approach was 19.5%. Calculating the population according to
      the land surface estimated by the latter method, the total Ethiopian population
      at risk for CL was estimated at 28,955,035, mainly including people in the
      highlands of the regional states of Amhara, Oromia, Tigray and the Southern
      Nations, Nationalities and Peoples' Region, one of the nine ethnic divisions in
      Ethiopia. Our environmental risk model provided an overall prediction accuracy of
      90.4%. The approach proposed here can be replicated for other diseases to
      facilitate implementation of evidence-based, integrated disease control
      activities.

PMID- 24893016
TI  - Importance of individual analysis of environmental and climatic factors affecting
      the density of Leishmania vectors living in the same geographical area: the
      example of Phlebotomus ariasi and P. perniciosus in northeast Spain.
AB  - The aim of the present study was to determine the role of specific environmental
      and climatic factors affecting the distribution and density of Phlebotomus ariasi
      and P. perniciosus , the proven vectors for Leishmania infantum in Spain. An
      entomological study was carried out in July 2006 in the province of Lleida with
      sticky traps set in their diurnal resting places at altitudes ranging from 86 to
      1,755 m above the mean sea level (339 sites were sampled). Bivariate analysis
      revealed that factors such as altitude, bioclimatic zone, temperature,
      precipitation, sampling site (site relative to settlement, site situation, site
      category), wall vegetation, particular environment (in this case a natural park),
      general environment, adjacent natural vegetation and land cover were
      significantly associated with sand fly densities. The multivariate model for P.
      perniciosus revealed that its density was affected by site and land cover.
      Specifically, paved driveways correlated negatively with vector density
      (Incidence Risk Ratio (IRR): 0.41) and arable land cover correlated positively
      (IRR: 4.59). In the case of P. ariasi, a significant correlation was observed
      with the altitude and bioclimatic zone, with density increasing at >800 m above
      the mean sea level (IRR: 3.40) and decreasing in the meso-Mediterranean
      bioclimatic zone (IRR: 0.08). Both species were mostly found in agricultural and
      forest areas far from domestic environments. However, the two species correlated
      differently with altitude, bio-climate, vegetation, temperature and
      precipitation, which emphasises the importance of their individual analysis in
      studies regarding risk of leishmaniasis transmission.

PMID- 24893017
TI  - Climate change and the potential global distribution of Aedes aegypti: spatial
      modelling using GIS and CLIMEX.
AB  - We examined the potential added risk posed by global climate change on the dengue
      vector Aedes aegypti abundance using CLIMEX, a powerful tool for exploring the
      relationship between the fundamental and realised niche of any species. After
      calibrating the model using data from several knowledge domains, including
      geographical distribution records, we estimated potential distributions of the
      mosquito under current and future potential scenarios. The impact of climate
      change on its potential distribution was assessed with two global climate models,
      the CSIRO-Mk3.0 and the MIROC-H, run with two potential, future emission
      scenarios (A1B and A2) published by the Intergovernmental Panel on Climate
      Change. We compared today's climate situation with two arbitrarily chosen future
      time points (2030 and 2070) to see the impact on the worldwide distribution of A.
      aegypti . The model for the current global climate indicated favourable areas for
      the mosquito within its known distribution in tropical and subtropical areas.
      However, even if much of the tropics and subtropics will continue to be suitable,
      the climatically favourable areas for A. aegypti globally are projected to
      contract under the future scenarios produced by these models, while currently
      unfavourable areas, such as inland Australia, the Arabian Peninsula, southern
      Iran and some parts of North America may become climatically favourable for this
      mosquito species. The climate models for the Aedes dengue vector presented here
      should be useful for management purposes as they can be adapted for
      decision/making regarding allocation of resources for dengue risk toward areas
      where risk infection remains and away from areas where climatic suitability is
      likely to decrease in the future. 

PMID- 24893018
TI  - Geospatial analysis of invasion of the Asian tiger mosquito Aedes albopictus:
      competition with Aedes japonicus japonicus in its northern limit area in Japan.
AB  - The mosquito Aedes albopictus, indigenous to Southeast Asia and nearby islands,
      has spread almost worldwide during recent decades. We confirm the invasion of
      this mosquito, first reported in Yamagata city in northeast Honshu, Japan in
      2000. Previously, only Ae. japonicus japonicus had been collected in this place,
      but 2 years later, the population of Ae. albopictus had increased, so more than
      80% of the total number of larval colonies there consisted of this species. In
      contrast to Yamagata's new residential area, now infested by Ae. albopictus, the
      original mosquito remains in the city but its habitats are generally closer to
      the surrounding mountains, where the normalized difference vegetation index is
      higher. The factors affecting the distribution of both species in Yamagata city
      were studied using geographical information systems (GIS) based on data derived
      from field surveys, aerial photographs, satellite images and digital maps. The
      range of Aedes mosquito habitats was estimated and visualised on polygon maps and
      no significant differences were noted when the polygon area was calculated by GIS
      software in comparison with the satellite images. Although Ae. j. japonicus was
      expected to be rapidly overrun by Ae. albopictus, this did not happen. Currently,
      both species coexist; not only in separate sites, but also simultaneously in
      various water bodies, where larvae from both species have frequently been seen.
      However, the competitive relationship between these two Aedes species within a
      warming environment is an issue that should be closely monitored. 

PMID- 24893019
TI  - Spatial distribution and risk factors of influenza in Jiangsu province, China,
      based on geographical information system.
AB  - Influenza poses a constant, heavy burden on society. Recent research has focused
      on ecological factors associated with influenza incidence and has also studied
      influenza with respect to its geographic spread at different scales. This
      research explores the temporal and spatial parameters of influenza and identifies
      factors influencing its transmission. A spatial autocorrelation analysis, a
      spatial-temporal cluster analysis and a spatial regression analysis of influenza
      rates, carried out in Jiangsu province from 2004 to 2011, found that influenza
      rates to be spatially dependent in 2004, 2005, 2006 and 2008. South-western
      districts consistently revealed hotspots of high-incidence influenza. The
      regression analysis indicates that railways, rivers and lakes are important
      predictive environmental variables for influenza risk. A better understanding of
      the epidemic pattern and ecological factors associated with pandemic influenza
      should benefit public health officials with respect to prevention and controlling
      measures during future epidemics. 

PMID- 24893020
TI  - The acquired immunodeficiency syndrome in the State of Rio de Janeiro, Brazil: a
      spatio-temporal analysis of cases reported in the period 2001-2010.
AB  - Despite increased funding for research on the human immunodeficiency virus (HIV)
      and the acquired immunodeficiency syndrome (AIDS), neither vaccine nor cure is
      yet in sight. Surveillance and prevention are essential for disease intervention,
      and it is recognised that spatio-temporal analysis of AIDS cases can assist the
      decision-making process for control of the disease. This study investigated the
      dynamic, spatial distribution of notified AIDS cases in the State of Rio de
      Janeiro, Brazil, between 2001 and 2010, based on the annual incidence in each
      municipality. Sequential choropleth maps were developed and used to analyse the
      incidence distribution and Moran's I spatial autocorrelation statistics was
      applied for characterisation of the spatio-temporal distribution pattern. A
      significant, positive spatial autocorrelation of AIDS incidence was observed
      indicating that municipalities with high incidence are likely to be close to
      other municipalities with similarly high incidence and, conversely,
      municipalities with low incidence are likely to be surrounded by municipalities
      with low incidence. Two clusters were identified; one hotspot related to the
      State Capital and the other with low to intermediate AIDS incidence comprising
      municipalities in the north-eastern region of the State of Rio de Janeiro. 

PMID- 24893021
TI  - Landscape attributes driving avian influenza virus circulation in the Lake
      Alaotra region of Madagascar.
AB  - While the spatial pattern of the highly pathogenic avian influenza H5N1 virus has
      been studied throughout Southeast Asia, little is known on the spatial risk
      factors for avian influenza in Africa. In the present paper, we combined
      serological data from poultry and remotely sensed environmental factors in the
      Lake Alaotra region of Madagascar to explore for any association between avian
      influenza and landscape variables. Serological data from cross-sectional surveys
      carried out on poultry in 2008 and 2009 were examined together with a Landsat 7
      satellite image analysed using supervised classification. The dominant landscape
      features in a 1-km buffer around farmhouses and distance to the closest water
      body were extracted. A total of 1,038 individual bird blood samples emanating
      from 241 flocks were analysed, and the association between avian influenza
      seroprevalence and these landcape variables was quantified using logistic
      regression models. No evidence of the presence of H5 or H7 avian influenza
      subtypes was found, suggesting that only low pathogenic avian influenza (LPAI)
      circulated. Three predominant land cover classes were identified around the
      poultry farms: grassland savannah, rice paddy fields and wetlands. A significant
      negative relationship was found between LPAI seroprevalence and distance to the
      closest body of water. We also found that LPAI seroprevalence was higher in farms
      characterised by predominant wetlands or rice landscapes than in those surrounded
      by dry savannah. Results from this study suggest that if highly pathogenic avian
      influenza H5N1 virus were introduced in Madagascar, the environmental conditions
      that prevail in Lake Alaotra region may allow the virus to spread and persist. 

PMID- 24893022
TI  - Retrospective space-time cluster analysis of whooping cough, re-emergence in
      Barcelona, Spain, 2000-2011.
AB  - A retrospective, space-time study of whooping cough cases reported to the Public
      Health Agency of Barcelona, Spain between the years 2000 and 2011 is presented.
      It is based on 633 individual whooping cough cases and the 2006 population census
      from the Spanish National Statistics Institute, stratified by age and sex at the
      census tract level. Cluster identification was attempted using space-time scan
      statistic assuming a Poisson distribution and restricting temporal extent to 7
      days and spatial distance to 500 m. Statistical calculations were performed with
      Stata 11 and SatScan and mapping was performed with ArcGis 10.0. Only clusters
      showing statistical significance (P <0.05) were mapped. The most likely cluster
      identified included five census tracts located in three neighbourhoods in central
      Barcelona during the week from 17 to 23 August 2011. This cluster included five
      cases compared with the expected level of 0.0021 (relative risk = 2436, P
      <0.001). In addition, 11 secondary significant space-time clusters were detected
      with secondary clusters occurring at different times and localizations. Spatial
      statistics is felt to be useful by complementing epidemiological surveillance
      systems through visualizing excess in the number of cases in space and time and
      thus increase the possibility of identifying outbreaks not reported by the
      surveillance system. 

PMID- 24893023
TI  - Spatial characterization of Leptospira spp. infection in equids from the Brejo
      Paraibano micro-region in Brazil.
AB  - The present study, the first to spatially characterize Leptospira spp. infection
      among equids in the Brejo Paraibano micro-region of the Paraiba state in the
      northeast of Brazil, investigated 257 animals in 26 farms properties. Serum
      samples from 204 horses, 46 mules and seven donkeys were serologically diagnosed
      using the microscopic agglutination test (MAT). The distribution of Leptospira
      spp. was studied by employing specific antigens from 24 different Leptospira
      serovars. All farms were georeferenced and their distribution visualised on a map
      of the Brejo Paraibano micro-region. In addition, rainfall data were obtained
      from the same year, in which the sampling was performed. Among the 20 farms found
      to harbour animals with leptospirosis, 14 (70%) exhibited low prevalence, five
      (25%) medium prevalence and one (5%), high prevalence. Certain areas had a higher
      density of infected farms and required intervention to control the infection.
      Many serovars were widely distributed, while others were more common in
      particular areas. There was no significant association between the prevalence of
      Leptospira spp. infection and rainfall. 

PMID- 24893024
TI  - Relative contributions of neighbourhood and animal movements to Coxiella burnetii
      infection in dairy cattle herds.
AB  - Q fever in dairy cattle herds occurs mainly after inhalation of contaminated
      aerosols generated from excreta by shedder animals. Propagation of Coxiella
      burnetii, the cause of the disease between ruminant herds could result from
      transmission between neighbouring herds and/or the introduction of infected
      shedder animals in healthy herds. The objective of this study were (i) to
      describe the spatial distribution C. burnetii-infected dairy cattle herds in two
      different regions: the Finistere District in France (2,829 herds) and the island
      of Gotland in Sweden (119 herds) and (ii) to quantify and compare the relative
      contributions of C. burnetii transmission related to neighbourhood and to animal
      movements on the risk for a herd to be infected. An enzyme--linked immunosorbent
      assay was used for testing bulk tank milk in May 2012 and June 2011,
      respectively. Only one geographical cluster of positive herds was identified in
      north-western Finistere. Logistic regression was used to assess the association
      of risk for a herd to test positively with local cattle density (the total number
      of cattle located in a 5 km radius circle) and the in-degree (ID) parameter, a
      measure of the number of herds from which each herd had received animals directly
      within the last 2 years. The risk for a herd to test positively was higher for
      herds with a higher local cattle density [odds ratio (OR) = 2.3, 95% confidence
      interval (CI) = 1.6-3.2, for herds with a local density between 100 and 120
      compared to herds with a local density 60]. The risk was also higher for herds
      with higher IDs (OR = 2.3, 95% CI = 1.6-3.2, for herds with ID 3 compared to
      herds that did not introduce animals). The proportion of cases attributable to
      infections in the neighbourhood in high-density areas was twice the proportion
      attributable to animal movements, suggesting that wind plays a main role in the
      transmission.

PMID- 24893025
TI  - Spatial epidemiology of Toxoplasma gondii infection in goats in Serbia.
AB  - A major risk factor for Toxoplasma gondii infection is consumption of undercooked
      meat. Increasing demand for goat meat is likely to promote the role of this
      animal for human toxoplasmosis. As there are virtually no data on toxoplasmosis
      in goats in Serbia, we undertook a cross-sectional serological study, including
      prediction modelling using geographical information systems (GIS). Sera from 431
      goats reared in 143 households/farms throughout Serbia, sampled between January
      2010 and September 2011, were examined for T. gondii antibodies by a modified
      agglutination test. Seroprevalence was 73.3% at the individual level and 84.6% at
      the farm level. Risk factor analysis showed above two-fold higher risk of
      infection for goats used for all purposes compared to dairy goats (P = 0.012),
      almost seven-fold higher risk for goats kept as sole species versus those kept
      with other animals (P = 0.001) and a two-fold lower risk for goats introduced
      from outside the farm compared to those raised on the farm (P = 0.027). Moreover,
      households/farms located in centre-eastern Serbia were found to be less often
      infected than those in northern Serbia (P = 0.004). The risk factor analysis was
      fully supported by spatial analysis based on a GIS database containing data on
      origin, serology, land cover, elevation, meteorology and a spatial prediction map
      based on kriging analysis, which showed western Serbia as the area most likely
      for finding goats positive for T. gondii and centre-eastern Serbia as the least
      likely. In addition, rainfall favoured seropositivity, whereas temperature,
      humidity and elevation did not. 

PMID- 24893026
TI  - Evaluation of the spatial patterns and risk factors, including backyard pigs, for
      classical swine fever occurrence in Bulgaria using a Bayesian model.
AB  - The spatial pattern and epidemiology of backyard pig farming and other low bio
      security pig production systems and their role in the occurrence of classical
      swine fever (CSF) is described and evaluated. A spatial Bayesian model was used
      to explore the risk factors, including human demographics, socioeconomic and
      environmental factors. The analyses were performed for Bulgaria, which has a
      large number of backyard farms (96% of all pig farms in the country are
      classified as backyard farms), and it is one of the countries for which both
      backyard pig and farm counts were available. Results reveal that the high-risk
      areas are typically concentrated in areas with small family farms, high numbers
      of outgoing pig shipments and low levels of personal consumption (i.e.
      economically deprived areas). Identification of risk factors and high-risk areas
      for CSF will allow to targeting risk-based surveillance strategies leading to
      prevention, control and, ultimately, elimination of the disease in Bulgaria and
      other countries with similar socio-epidemiological conditions. 

PMID- 24893027
TI  - Temporal and spatial mapping of hand, foot and mouth disease in Sarawak,
      Malaysia.
AB  - Hand, foot and mouth disease (HFMD) is endemic in Sarawak, Malaysia. In this
      study, a geographical information system (GIS) was used to investigate the
      relationship between the reported HFMD cases and the spatial patterns in 11
      districts of Sarawak from 2006 to 2012. Within this 7-years period, the highest
      number of reported HFMD cases occurred in 2006, followed by 2012, 2008, 2009,
      2007, 2010 and 2011, in descending order. However, while there was no significant
      distribution pattern or clustering in the first part of the study period (2006 to
      2011) based on Moran's I statistic, spatial autocorrelation (P = 0.068) was
      observed in 2012. 

PMID- 24893028
TI  - Retrospective and spatial analysis tools for integrated surveillance of cystic
      echinococcosis and bovine cysticercosis in hypo-endemic areas.
AB  - Cystic echinococcosis (CE) and bovine cysticercosis (BC) are two important
      parasitic zoonoses, whose prevalence varies among European countries. Few data
      are available on prevalence and geographic distribution of these two diseases in
      Veneto region in North-Eastern Italy, where they are generally perceived as minor
      public health problems. Available data from regional farms on cattle positive to
      CE and BC and slaughtered in the period 2006-2010 were analysed by spatial scan
      statistic using a Bernoulli probablility model. Out of 576 bovines testing
      positive to CE, 467 were found to be autochthonous cases. Three significant CE
      clusters were identified, the most likely one (P < 0.0001) located in the eastern
      part of the Veneto region. As for BC, two clusters were identified from 148
      animals resting positive, 91 which were autochthonous. An epidemiological survey
      was conducted and the most likely CE cluster was centered, collecting faecal
      samples from 28 dogs living in the farms of the area. Out of five animals (all
      shepherd dogs) found positive for taenid eggs by copromicroscopy, one was
      confirmed positive for Echinoccus granulosus by means of polymerase chain
      reaction. The study demonstrates the usefulness of integration of slaughterhouse
      data and geographical coordinates of farms involved for effective surveillance of
      CE and BC. The reliability of the spatial analysis in the identification of
      clusters of EC cases was confirmed by the finding of one dog positive for E.
      granulosus.

PMID- 24893029
TI  - Cluster detection of diseases in heterogeneous populations: an alternative to
      scan methods.
AB  - Cluster detection has become an important part of the agenda of epidemiologists
      and public health authorities, the identification of high- and low-risk areas is
      fundamental in the definition of public health strategies and in the suggestion
      of potential risks factors. Currently, there are different cluster detection
      techniques available, the most popular being those using windows to scan the
      areas within the studied region. However, when these areas are heterogeneous in
      populations' sizes, scan window methods can lead to inaccurate conclusions. In
      order to perform cluster detection over heterogeneously populated areas, we
      developed a method not based on scanning windows but instead on standard
      mortality ratios (SMR) using irregular spatial aggregation (ISA). Its extension,
      i.e. irregular spatial aggregation with covariates (ISAC), includes covariates
      with residuals from Poisson regression. We compared the performance of the method
      with the flexible shaped spatial scan statistic (FlexScan) using mortality data
      for stomach and bladder cancer for 8,098 Spanish towns. The results show a
      collection of clusters for stomach and bladder cancer similar to that detected by
      ISA and FlexScan. However, in general, clusters detected by FlexScan were bigger
      and include towns with SMR, which were not statistically significant. For bladder
      cancer, clusters detected by ISAC differed from those detected by ISA and
      FlexScan in shape and location. The ISA and ISAC methods could be an alternative
      to the traditional scan window methods for cluster detection over aggregated data
      when the areas under study are heterogeneous in terms of population. The
      simplicity and flexibility of the methods make them more attractive than methods
      based on more complicated algorithms. 

PMID- 24893030
TI  - Methodological approach in determination of small spatial units in a highly
      complex terrain in atmospheric pollution research: the case of Zasavje region in
      Slovenia.
AB  - The study of atmospheric air pollution research in complex terrains is challenged
      by the lack of appropriate methodology supporting the analysis of the spatial
      relationship between phenomena affected by a multitude of factors. The key is
      optimal design of a meaningful approach based on small spatial units of
      observation. The Zasavje region, Slovenia, was chosen as study area with the main
      objective to investigate in practice the role of such units in a test
      environment. The process consisted of three steps: modelling of pollution in the
      atmosphere with dispersion models, transfer of the results to geographical
      information system software, and then moving on to final determination of the
      function of small spatial units. A methodology capable of designing useful units
      for atmospheric air pollution research in highly complex terrains was created,
      and the results were deemed useful in offering starting points for further
      research in the field of geospatial health. 

PMID- 24893031
TI  - Hospital distribution in a metropolitan city: assessment by a geographic
      information system grid modelling approach.
AB  - Grid models were used to assess urban hospital distribution in Seoul, the capital
      of South Korea. A geographical information system (GIS) based analytical model
      was developed and applied to assess the situation in a metropolitan area with a
      population exceeding 10 million. Secondary data for this analysis were obtained
      from multiple sources: the Korean Statistical Information Service, the Korean
      Hospital Association and the Statistical Geographical Information System. A grid
      of cells measuring 1 * 1 km was superimposed on the city map and a set of
      variables related to population, economy, mobility and housing were identified
      and measured for each cell. Socio-demographic variables were included to reflect
      the characteristics of each area. Analytical models were then developed using GIS
      software with the number of hospitals as the dependent variable. Applying
      multiple linear regression and geographically weighted regression models, three
      factors (highway and major arterial road areas; number of subway entrances; and
      row house areas) were statistically significant in explaining the variance of
      hospital distribution for each cell. The overall results show that GIS is a
      useful tool for analysing and understanding location strategies. This approach
      appears a useful source of information for decision-makers concerned with the
      distribution of hospitals and other health care centres in a city. 

PMID- 24893032
TI  - Spatial access to inpatient health care in northern rural India.
AB  - Access to health care in rural areas is a major concern for local populations as
      well as for policy makers in developing countries. This paper examines spatial
      access to in-patient health care in northern rural India. In order to measure
      spatial access, impedance-based competition using the Three-Step floating
      Catchment Area (3SFCA) method, a modification of the simple gravity model, was
      used. 3SFCA was chosen for the study of the districts of Pratapgarh and Kanpur
      Dehat in the Uttar Pradesh state and Vaishali in the Bihar state, two of India's
      poorest states. This approach is based on discrete distance decay and also
      considers more parameters than other available methods, hence is believed to be a
      robust methodology. It was found that Vaishali district has the highest spatial
      access to in-patient health care followed by Pratapgarh and Kanpur Dehat. There
      is serious lack of health care, in Pratapgarh and Kanpur Dehat with 40% and 90%
      of the villages having shortage of in-patient care facilities in these respective
      districts. The most important factor affecting spatial access was found to be the
      distance to the nearest major urban agglomeration. 

PMID- 24893034
TI  - The physical environment and health-enhancing activity during the school commute:
      global positioning system, geographical information systems and accelerometry.
AB  - Active school travel is in decline. An understanding of the potential
      determinants of health-enhancing physical activity during the school commute may
      help to inform interventions aimed at reversing these trends. The purpose of this
      study was to identify the physical environmental factors associated with health
      enhancing physical activity during the school commute. Data were collected in
      2009 on 166 children commuting home from school in Scotland. Data on location and
      physical activity were measured using global positioning systems (GPS) and
      accelerometers, and mapped using geographical information systems (GIS). Multi
      level logistic regression models accounting for repeated observations within
      participants were used to test for associations between each land-use category
      (road/track/path, other man-made, greenspace, other natural) and moderate-to
      vigorous physical activity (MVPA). Thirty-nine children provided 2,782 matched
      data points. Over one third (37.1%) of children's school commute time was spent
      in MVPA. Children commuted approximately equal amounts of time via natural and
      man-made land-uses (50.2% and 49.8% respectively). Commuting via road/track/path
      was associated with increased likelihood of MVPA (Exp(B)=1.23, P <0.05), but this
      association was not seen for commuting via other manmade land-uses. No
      association was noted between greenspace use and MVPA, but travelling via other
      natural land-uses was associated with lower odds of MVPA (Exp(B)=0.32, P <0.05).
      Children spend equal amounts of time commuting to school via man-made and natural
      land-uses, yet man-made transportation route infrastructure appears to provide
      greater opportunities for achieving health-enhancing physical activity levels. 

PMID- 24893035
TI  - Optimizing denominator data estimation through a multimodel approach.
AB  - To assess the risk of (zoonotic) disease transmission in developing countries,
      decision makers generally rely on distribution estimates of animals from survey
      records or projections of historical enumeration results. Given the high cost of
      large-scale surveys, the sample size is often restricted and the accuracy of
      estimates is therefore low, especially when spatial high-resolution is applied.
      This study explores possibilities of improving the accuracy of livestock
      distribution maps without additional samples using spatial modelling based on
      regression tree forest models, developed using subsets of the Uganda 2008
      Livestock Census data, and several covariates. The accuracy of these spatial
      models as well as the accuracy of an ensemble of a spatial model and direct
      estimate was compared to direct estimates and "true" livestock figures based on
      the entire dataset. The new approach is shown to effectively increase the
      livestock estimate accuracy (median relative error decrease of 0.166-0.037 for
      total sample sizes of 80-1,600 animals, respectively). This outcome suggests that
      the accuracy levels obtained with direct estimates can indeed be achieved with
      lower sample sizes and the multimodel approach presented here, indicating a more
      efficient use of financial resources. 

PMID- 24893033
TI  - When homogeneity meets heterogeneity: the geographically weighted regression with
      spatial lag approach to prenatal care utilization.
AB  - Using geographically weighted regression (GWR), a recent study by Shoff and
      colleagues (2012) investigated the place-specific risk factors for prenatal care
      utilisation in the United States of America (USA) and found that most of the
      relationships between late or no prenatal care and its determinants are spatially
      heterogeneous. However, the GWR approach may be subject to the confounding effect
      of spatial homogeneity. The goal of this study was to address this concern by
      including both spatial homogeneity and heterogeneity into the analysis.
      Specifically, we employed an analytic framework where a spatially lagged (SL)
      effect of the dependent variable is incorporated into the GWR model, which is
      called GWR-SL. Using this framework, we found evidence to argue that spatial
      homogeneity is neglected in the study by Shoff et al. (2012) and that the results
      change after considering the SL effect of prenatal care utilisation. The GWR-SL
      approach allowed us to gain a placespecific understanding of prenatal care
      utilisation in USA counties. In addition, we compared the GWR-SL results with the
      results of conventional approaches (i.e., ordinary least squares and spatial lag
      models) and found that GWR-SL is the preferred modelling approach. The new
      findings help us to better estimate how the predictors are associated with
      prenatal care utilisation across space, and determine whether and how the level
      of prenatal care utilisation in neighbouring counties matters. 

PMID- 24893036
TI  - A conceptual holding model for veterinary applications.
AB  - Spatial references are required when geographical information systems (GIS) are
      used for the collection, storage and management of data. In the veterinary
      domain, the spatial component of a holding (of animals) is usually defined by
      coordinates, and no other relevant information needs to be interpreted or used
      for manipulation of the data in the GIS environment provided. Users trying to
      integrate or reuse spatial data organised in such a way, frequently face the
      problem of data incompatibility and inconsistency. The root of the problem lies
      in differences with respect to syntax as well as variations in the semantic,
      spatial and temporal representations of the geographic features. To overcome
      these problems and to facilitate the inter-operability of different GIS, spatial
      data must be defined according to a ?"schema?" that includes the definition,
      acquisition, analysis, access, presentation and transfer of such data between
      different users and systems. We propose an application ?"schema?" of holdings for
      GIS applications in the veterinary domain according to the European directive
      framework (directive 2007/2/EC--INSPIRE). The conceptual model put forward has
      been developed at two specific levels to produce the essential and the abstract
      model, respectively. The former establishes the conceptual linkage of the system
      design to the real world, while the latter describes how the system or software
      works. The result is an application ?"schema?" that formalises and unifies the
      information-theoretic foundations of how to spatially represent a holding in
      order to ensure straightforward information-sharing within the veterinary
      community.

PMID- 24893039
TI  - Helicobacter pylori CagL Y58/E59 mutation turns-off type IV secretion-dependent
      delivery of CagA into host cells.
AB  - The type IV secretion system (T4SS) is a major virulence determinant of the
      gastric pathogen Helicobacter pylori. The CagL protein is a specialized adhesin
      of the corresponding T4SS pilus, which establishes initial contact with the
      integrin beta1 receptor on host target cells. Recent studies proposed that Y58
      and E59 amino acid polymorphisms in CagL increase the virulence of H. pylori
      strains by enhanced translocation and phosphorylation of the CagA effector
      protein. These polymorphisms were therefore correlated with an increased risk of
      gastric cancer development. Here we show that the Y58/E59 motif, which is located
      in a loop connecting two alpha-helices, and corresponding polymorphisms could
      influence the function of CagL. However, expression of isogenic CagL Y58/E59
      variants in H. pylori strain 26695 significantly blocked the translocation and
      phosphorylation of CagA as compared to complemented wild-type CagL. These results
      suggest that the function of the T4SS for delivery of CagA is turned-off by the
      Y58/E59 mutation in CagL. This activity appears to be similar to the one recently
      described for another T4SS pilus protein, CagY, which is also sufficient to cause
      gain or loss of T4SS function. These data support the hypothesis that certain
      mutations in CagL or recombination events in CagY may serve as a sort of
      molecular switch or perhaps rheostat in the T4SS, which could alter the function
      of the pilus and "tunes" injection of CagA and host pro-inflammatory responses,
      respectively. 

PMID- 24893038
TI  - Carbon ion radiation inhibits glioma and endothelial cell migration induced by
      secreted VEGF.
AB  - This study evaluated the effects of carbon ion and X-ray radiation and the tumor
      microenvironment on the migration of glioma and endothelial cells, a key process
      in tumorigenesis and angiogenesis during cancer progression. C6 glioma and human
      microvascular endothelial cells were treated with conditioned medium from
      cultures of glioma cells irradiated at a range of doses and the migration of both
      cell types, tube formation by endothelial cells, as well as the expression and
      secretion of migration-related proteins were evaluated. Exposure to X-ray
      radiation-conditioned medium induced dose-dependent increases in cell migration
      and tube formation, which were accompanied by an upregulation of vascular
      endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and -9
      expression. However, glioma cells treated with conditioned medium of cells
      irradiated at a carbon ion dose of 4.0 Gy showed a marked decrease in migratory
      potential and VEGF secretion relative to non-irradiated cells. The application of
      recombinant VEGF165 stimulated migration in glioma and endothelial cells, which
      was associated with increased FAK phosphorylation at Tyr861, suggesting that the
      suppression of cell migration by carbon ion radiation could be via VEGF-activated
      FAK signaling. Taken together, these findings indicate that carbon ion may be
      superior to X-ray radiation for inhibiting tumorigenesis and angiogenesis through
      modulation of VEGF level in the glioma microenvironment. 

PMID- 24893040
TI  - Factors that affect intravenous patient-controlled analgesia for postoperative
      pain following orthognathic surgery for mandibular prognathism.
AB  - The predictors of postoperative pain and analgesic consumption were previously
      found to include preoperative pain, anxiety, age, type of surgery, and genotype,
      but remaining unclear was whether intraoperative factors could predict
      postoperative pain. In the present study, we investigated the time-course of
      fentanyl consumption using intravenous patient-controlled analgesia records from
      patients who underwent orthognathic surgery for mandibular prognathism and
      analyzed the influence of anesthesia methods and surgical methods together with
      sex on the time course. A significant difference in the time course of fentanyl
      administration was found (P<0.001). No significant difference in the time course
      of fentanyl administration was found between males and females (P = 0.653), with
      no interaction between time course and sex (P = 0.567). No significant difference
      in the time course of fentanyl administration was found among anesthesia methods,
      such as fentanyl induction followed by fentanyl maintenance, fentanyl induction
      followed by remifentanil maintenance, and remifentanil induction followed by
      remifentanil maintenance (P = 0.512), but an interaction between time course and
      anesthesia method was observed (P = 0.004). A significant difference in the time
      course of fentanyl administration was found between surgical methods, such as
      bilateral mandibular sagittal split ramus osteotomy (BSSRO) and BSSRO combined
      with Le Fort I osteotomy (bimaxillary; P = 0.008), with no interaction between
      time course and surgical method (P = 0.535). Total postoperative 24 h consumption
      associated with the bimaxillary procedure was significantly higher than with
      BSSRO (P = 0.008). The present results indicate that administration patterns and
      total 24 h consumption were different among the three groups of anesthesia
      methods and between the two groups of surgical methods, respectively. Although
      more research on patient-controlled analgesia patterns and consumption is
      necessary, the present study will contribute to adequately relieving individual
      patients from postoperative pain.

PMID- 24893041
TI  - Unmet needs in the treatment of mantle cell lymphoma.
AB  - Mantle cell lymphoma is one of the most challenging hematologic malignancies,
      owing to an aggressive disease course, a high rate of relapse, and lack of
      standard of care. In the United States, mantle cell lymphoma accounts for
      approximately 6% of all newly diagnosed cases of non-Hodgkin lymphoma. Because
      most patients are initially diagnosed with advanced-stage disease, they are often
      symptomatic at presentation. Common features include widespread lymphadenopathy
      and splenomegaly, as well as bone marrow infiltration. Leukemic involvement is
      found in 20% to 30% of patients. The disease course can be highly variable. Some
      patients may have very aggressive disease, whereas others may have a much more
      indolent course. The optimal frontline therapy remains undefined. Strategies
      include chemotherapy, immunotherapy, radioimmunotherapy, stem cell
      transplantation, and novel biologic agents. Although mantle cell lymphoma often
      responds well to frontline chemotherapy, the responses are not durable and often
      of relatively short duration. Effective treatment options in the frontline
      setting have included the addition of rituximab to bendamustine. Once mantle cell
      lymphoma has entered the relapsed/refractory stage, it becomes more difficult to
      treat. Bortezomib and lenalidomide are approved for treatment of
      relapsed/refractory mantle cell lymphoma. The novel Bruton's tyrosine kinase
      inhibitor ibrutinib appears to be highly active in relapsed/refractory mantle
      cell lymphoma. Other agents in clinical trials include cladribine, idelalisib,
      and IPI-145.

PMID- 24893045
TI  - Cytotoxic, biochemical and genotoxic effects of biodiesel produced by different
      routes on ZFL cell line.
AB  - Transesterification has proved to be the best option for obtaining biodiesel and,
      depending on the type of alcohol used in the reaction, the type of biodiesel may
      be methyl ester or ethyl ester. Leaking biodiesel can reach water bodies,
      contaminating aquatic organisms, particularly fish. The objective of this study
      was to determine whether the soluble fraction of biodiesel (Bd), produced by both
      the ethylic (BdEt) and methylic (BdMt) routes, can cause cytotoxic, biochemical
      and genotoxic alterations in the hepatocyte cell line of Danio rerio (ZFL). The
      metabolic activity of the cell was quantified by the MTT reduction method, while
      genotoxic damage was analyzed by the comet assay with the addition of specific
      endonucleases. The production of reactive oxygen species (ROS) and
      antioxidant/biotransformation enzymes activity also were determined. The results
      indicate that both Bd increased ROS production, glutathione S-transferase
      activity and the occurrence of DNA damage. BdMt showed higher cytotoxicity than
      BdEt, and also caused oxidative damage to the DNA. In general, both Bd appear to
      be stressors for the cells, causing cytotoxic, biochemical and genetic
      alterations in ZFL cells, but the type and intensity of the changes found appear
      to be dependent on the biodiesel production route. 

PMID- 24893046
TI  - The skeleton of the staghorn coral Acropora millepora: molecular and structural
      characterization.
AB  - The scleractinian coral Acropora millepora is one of the most studied species
      from the Great Barrier Reef. This species has been used to understand
      evolutionary, immune and developmental processes in cnidarians. It has also been
      subject of several ecological studies in order to elucidate reef responses to
      environmental changes such as temperature rise and ocean acidification (OA). In
      these contexts, several nucleic acid resources were made available. When combined
      to a recent proteomic analysis of the coral skeletal organic matrix (SOM), they
      enabled the identification of several skeletal matrix proteins, making A.
      millepora into an emerging model for biomineralization studies. Here we describe
      the skeletal microstructure of A. millepora skeleton, together with a functional
      and biochemical characterization of its occluded SOM that focuses on the protein
      and saccharidic moieties. The skeletal matrix proteins show a large range of
      isoelectric points, compositional patterns and signatures. Besides secreted
      proteins, there are a significant number of proteins with membrane attachment
      sites such as transmembrane domains and GPI anchors as well as proteins with
      integrin binding sites. These features show that the skeletal proteins must have
      strong adhesion properties in order to function in the calcifying space. Moreover
      this data suggest a molecular connection between the calcifying epithelium and
      the skeletal tissue during biocalcification. In terms of sugar moieties, the
      enrichment of the SOM in arabinose is striking, and the monosaccharide
      composition exhibits the same signature as that of mucus of acroporid corals.
      Finally, we observe that the interaction of the acetic acid soluble SOM on the
      morphology of in vitro grown CaCO3 crystals is very pronounced when compared with
      the calcifying matrices of some mollusks. In light of these results, we wish to
      commend Acropora millepora as a model for biocalcification studies in
      scleractinians, from molecular and structural viewpoints. 

PMID- 24893048
TI  - MR elastography for the assessment of hepatic fibrosis in patients with chronic
      hepatitis B infection: does histologic necroinflammation influence the
      measurement of hepatic stiffness?
AB  - PURPOSE: To determine the diagnostic performance of magnetic resonance (MR)
      elastography for the staging of hepatic fibrosis and to evaluate the influence of
      necroinflammation on hepatic stiffness in patients with chronic hepatitis B virus
      (HBV) infection by using histopathologic findings as the reference standard.
      MATERIALS AND METHODS: One hundred thirteen consecutive patients with chronic HBV
      infection were recruited prospectively in this institutional review board
      approved study after providing written informed consent between March 2012 and
      October 2013. The stiffness measurements were obtained by using two-dimensional
      gradient-echo MR elastography with a 3.0-T MR system. The METAVIR scoring system
      was used for the assessment of fibrosis ("F" stage) and necroinflammation ("A"
      grade). The predictive ability of MR elastography was evaluated by using the
      receiver operating characteristic (ROC) curve and the area under the ROC curve
      (AUC). Multiple linear regression analyses were conducted to determine the
      relationship between hepatic stiffness and the variables that showed a
      significant association in the univariate analysis or those that were of interest
      for comparison with earlier work (histologic scores, sex, age, aspartate
      aminotransferase level, and aspartate aminotransferase/alanine aminotransferase
      ratio). RESULTS: MR elastography showed excellent performance for
      characterization of >= F1, >= F2, >= F3, and F4 findings, with AUC values of
      0.961, 0.986, 1.000, and 0.998, respectively. It showed a moderate capability for
      evaluation of necroinflammatory activity of >= A1, >= A2, and A3 (AUC = 0.806,
      0.834, and 0.906, respectively). Multiple linear regression analysis showed that
      fibrosis, necroinflammation, and sex were independently associated with hepatic
      stiffness (beta = 0.799, 0.277, and 0.070, respectively; P < .05). For pairwise
      comparisons, log-transformed hepatic stiffness showed no difference between (a)
      groups F0/A2-3 and F1/A0-1 and (b) groups F1/A2-3 and F2/A0-1 (P > .99 and P =
      .486, respectively). CONCLUSION: MR elastography demonstrated excellent
      performance for distinguishing the stages of hepatic fibrosis in patients with
      chronic HBV infection. For hepatic tissue with <= F2 fibrosis, necroinflammation
      can account for a substantial fraction of the increase in hepatic stiffness.

PMID- 24893050
TI  - Healthy aging and intergenerational solidarity - Latin America and its moment of
      opportunity.

PMID- 24893049
TI  - Metastases in normal-sized pelvic lymph nodes: detection with diffusion-weighted
      MR imaging.
AB  - PURPOSE: To prospectively assess the diagnostic performance of diffusion-weighted
      (DW) magnetic resonance (MR) imaging in the detection of pelvic lymph node
      metastases in patients with prostate and/or bladder cancer staged as N0 with
      preoperative cross-sectional imaging. MATERIALS AND METHODS: This study was
      approved by an independent ethics committee. Written informed consent was
      obtained from all patients. Patients with no enlarged lymph nodes on preoperative
      cross-sectional images who were scheduled for radical resection of the primary
      tumor and extended pelvic lymph node dissection were enrolled. All patients were
      examined with a 3-T MR unit, and examinations included conventional and DW MR
      imaging of the entire pelvis. Image analysis was performed by three independent
      readers blinded to any clinical information. Metastases were diagnosed on the
      basis of high signal intensity on high b value DW MR images and morphologic
      features (shape, border). Histopathologic examination served as the standard of
      reference. Sensitivity and specificity were calculated, and bias-corrected 95%
      confidence intervals (CIs) were obtained with the bootstrap method. The Fleiss
      and Cohen kappa and median test were applied for statistical analyses. RESULTS: A
      total of 4846 lymph nodes were resected in 120 patients. Eighty-eight lymph node
      metastases were found in 33 of 120 patients (27.5%). Short-axis diameter of these
      metastases was less than or equal to 3 mm in 68, more than 3 mm to 5 mm in 13,
      more than 5 mm to 8 mm in five; and more than 8 mm in two. On a per-patient
      level, the three readers correctly detected metastases in 26 (79%; 95% CI: 64%,
      91%), 21 (64%; 95% CI: 45%, 79%), and 25 (76%; 95% CI: 60%, 90%) of the 33
      patients with metastases, with respective specificities of 85% (95% CI: 78%,
      92%), 79% (95% CI: 70%, 88%), and 84% (95% CI: 76%, 92%). Analyzed according to
      hemipelvis, lymph node metastases were detected with histopathologic examination
      in 44 of 240 pelvic sides (18%); the three readers correctly detected these on DW
      MR images in 26 (59%; 95% CI: 45%, 73%), 19 (43%; 95% CI: 27%, 57%), and 28 (64%;
      95% CI: 47%, 78%) of the 44 cases. CONCLUSION: DW MR imaging enables noninvasive
      detection of small lymph node metastases in normal-sized nodes in a substantial
      percentage of patients with prostate and bladder cancer diagnosed as N0 with
      conventional cross-sectional imaging techniques.

PMID- 24893051
TI  - Afebrile pneumonia (whooping cough) syndrome in infants at Hospital Universitario
      del Valle, Cali, 2001-2007.
AB  - INTRODUCTION: Afebrile pneumonia syndrome in infants, also called infant
      pneumonitis, pneumonia caused by atypical pathogens or whooping cough syndrome is
      a major cause of severe lower respiratory infection in young infants, both in
      developing countries and in developed countries. OBJECTIVE: To describe children
      with afebrile pneumonia syndrome. METHODS: Through a cross-sectional study, we
      reviewed the medical records of children diagnosed with afebrile pneumonia
      treated at Hospital Universitario del Valle, a reference center in southwestern
      Colombia, between June 2001 and December 2007. We obtained data on maternal age
      and origin, prenatal care, the childs birth, breastfeeding, vaccination status,
      symptoms, signs, diagnosis, treatment, and complications. RESULTS: We evaluated
      101 children with this entity, noting a stationary presentation: June-August and
      November- December. A total of 73% of the children were under 4 months of age;
      the most common symptoms were: cyanotic and spasmodic cough (100%), respiratory
      distress (70%), and unquantified fever (68%). The most common findings: rales
      (crackles) (50%), wheezing and expiratory stridor (37%); 66% were classified as
      mild and of the remaining 33%, half of them required attention in the intensive
      care unit. In all, there was clinical diagnosis of afebrile pneumonia syndrome in
      infants, but no etiologic diagnosis was made and despite this, 94% of the
      children received macrolides. CONCLUSIONS: These data support the hypothesis that
      most of these patients acquired the disease by airway, possibly caused by viral
      infection and did not require the indiscriminate use of macrolides.

PMID- 24893052
TI  - Normal values of the maximal respiratory pressures in healthy people older than
      20 years old in the City of Manizales - Colombia.
AB  - INTRODUCTION: The Maximal Inspiratory Pressure (MIP) and Maximal Expiratory
      Pressure (MEP) are global measures of the maximal strength of the respiratory
      muscles. OBJECTIVES: To determine the values of MIP and MEP in healthy subjects
      aged 20 years old from the urban area of Manizales, Colombia and to correlate
      them with sociodemographic and anthropometric variables. METHODS: This is an
      observational descriptive study. The population of the study was 203,965 healthy
      people from Manizales, a Colombian city located at 2,150 meters above sea level.
      The sample size was 308 subjects, selected using simple random sampling. The
      maximal respiratory pressures were determined in the sample chosen and were then
      considered according to the variables of age, gender, size, weight, Body Mass
      Index (BMI), and BMI classification. Finally a predictive model was created.
      RESULTS: The average MIP value among the subjects of the study was 75+/-27 cmH20
      and the MEP value was 96.4+/-36 cmH20. Both averages were higher in men than in
      women. Predictive equations were established for the normal values of MIP and MEP
      in healthy subjects; the best model for MIP was the resultant one among age,
      gender and BMI classification and for the MEP among gender, weight and height.
      CONCLUSION: Maximal respiratory pressure values were lower among the population
      of Manizales than those found in international studies. Gender and anthropometric
      characteristics (weight, height and BMI classification) are the explanatory
      variables that better support the average values of MIP and MEP in the predictive
      models proposed.

PMID- 24893053
TI  - Socio-demographic transformations and living conditions among two indigenous and
      black populations in Northern Cauca during the period of 1993-2005.
AB  - OBJECTIVES: To describe the changes that occurred in some patterns of socio
      demographic variables and in living conditions among the Nasa, Guambiana and
      Afrocolombian populations in the northern region of the Department of Cauca, and
      those occurring in two residential communities, one white-mestizo and one black,
      in Cali during the 1993-2005 period. METHODS: This paper presents a descriptive
      study that analyzes several socio-demographic indicators from the census of 1993
      and 2005, the specific data include: rate of juvenile dependency; total
      masculinity index; average size of the household; specific global and local birth
      rates, and infant mortality rates; life expectancy at birth; average years of
      schooling; health cover age status; and percentage of the population with unmet
      basic needs (UBN). In this way, it is possible to note differences in the course
      of socio-demographic evolution and in the standard of living trends in the
      differing populations under study. RESULTS: The Guambiana Indian population in
      the municipality of Silvia presents lower birth rates than the Nasa population,
      characterized by their seasonal birth rates. Differing from the pattern of the
      indigenous people of Northern Cauca, the Afro-Colombian population both from this
      region and from the population residing in the urban zones of Cali's tend to show
      similar socio-demographic patterns. CONCLUSIONS: Although there have been
      profound changes recorded during this period among these populations under study,
      the ethnic-racial inequalities and those of social class seem to persist. From
      this first diagnosis, attention is called to the need for a more adequate
      reproductive health policy to attend the specific needs presented by the
      indigenous population.

PMID- 24893054
TI  - Diversity and genetic structure analysis of three Amazonian Amerindian
      populations of Colombia.
AB  - INTRODUCTION: In the departments of the Vaupes and Guaviare, in southeastern
      Colombia, in a transitional area between Amazonia and the eastern plains, inhabit
      indigenous groups belonging to the Tukanoan (East) and Guahiban linguistic
      families. Although some studies have dealt with the culture and the cosmology
      description of these groups, little research has been done on the biological
      diversity and genetic relationships of such groups. OBJECTIVE: To estimate the
      diversity, the structure, and the genetic relationships of one Guahiban and two
      Tukanoan groups of the Colombian Amazonian region. METHODS: Samples were
      collected (n = 106) from unrelated individuals belonging to the Vaupes native
      indigenous communities. The DNA was extracted and nine autosomal microsatellites
      were typed. Several measures of diversity, FST, pairwise FST, and population
      differentiation between groups were calculated. Finally, it was estimated the
      genetic distances of the groups studied in relation with other Amazonian, Andean
      and Central American indigenous people. RESULTS: 1. The genetic diversity found
      stands within the range of other Amazonian populations, whereas compared to the
      mestizo and afro-descendant Colombian populations, such diversity showed to be
      lower. 2. The structure and population differentiation tests showed two clusters;
      one consisting of the Vaupes Tukanoan and Guaviare Tukanoan groups, and a second
      one formed by the Guayabero. 3. Tukanoan groups are found to be closer related to
      the Brazilian Amazonian populations than to the Guayabero. CONCLUSION: The
      results of this study suggest that the Guayabero group from Guaviare, are
      genetically differentiated from those Tukanoan groups of the Vaupes and Guaviare.

PMID- 24893055
TI  - Prevalence of flatfoot in school between 3 and 10 years. Study of two different
      populations geographically and socially.
AB  - INTRODUCTION: Children present with flatfoot from birth and it resolves along
      infancy. There have been several risk factors identified for the development of
      flatfoot: male sex, young age, overweight and obesity. The prevalence of flatfoot
      decreases with age. The aim of this study was to determine the prevalence of
      flatfoot in two different populations with different social, cultural and
      geographically characteristics in Colombia. METHODS: This is a cross sectional
      study made on school children between 3 to 10 years of age, from several schools
      in Bogota and Barranquilla. From 940 total children 60% were from Bogota.
      Flatfoot was diagnosed according to physical exam. RESULTS: We found a global
      prevalence of flatfoot of 15.7%, distributed 20.8% in Bogota and 7.9% in
      Barranquilla. The children from 3 to 5 years had a prevalence of 30.9%,
      decreasing significantly after this age. It was found that children 3 to 5 years
      old from Bogota had a prevalence of flatfoot of 38.3% while children from
      Barranquilla only 17.3%, decreasing significantly in children older than 6 years.
      In the multivariate analysis we found an association between flatfoot with age,
      city, gender and body mass index. DISCUSSION: We found a bigger prevalence of
      flatfoot in the population of Bogota compared to Barranquilla suggesting an
      influence of social, cultural and racial factors in the development of flatfoot.
      The diminished prevalence of flatfoot in children over 6 years of age suggest
      that therapeutic measures before this age are not recommended.

PMID- 24893056
TI  - Incidence of nutritional support complications in patient hospitalized in wards.
      multicentric study.
AB  - INTRODUCTION: Nutritional support generates complications that must be detected
      and treated on time. OBJECTIVE: To estimate the incidence of some complications
      of nutritional support in patients admitted to general hospital wards who
      received nutritional support in six high-complexity institutions. METHODS:
      Prospective, descriptive and multicentric study in patients with nutritional
      support; the variables studied were medical diagnosis, nutritional condition,
      nutritional support duration, approach, kind of formula, and eight complications.
      RESULTS: A total of 277 patients were evaluated; 83% received enteral nutrition
      and 17% received parenteral nutrition. Some 69.3% presented risk of
      malnourishment or severe malnourishment at admittance. About 35.4% of those
      receiving enteral nutrition and 39.6% of the ones who received parenteral
      nutrition had complications; no significant difference per support was found (p=
      0.363). For the enteral nutrition, the most significant complication was the
      removal of the catheter (14%), followed by diarrhea (8.3%); an association
      between the duration of the enteral support with diarrhea, constipation and
      removal of the catheter was found (p < 0.05). For parenteral nutrition,
      hyperglycemia was the complication of highest incidence (22.9%), followed by
      hypophosphatemia (12.5%); all complications were associated with the duration of
      the support (p < 0.05). Nutritional support was suspended in 24.2% of the
      patients. CONCLUSIONS: Complications with nutritional support in hospital-ward
      patients were frequent, with the removal of the catheter and hyperglycemia
      showing the highest incidence. Duration of the support was the variable that
      revealed an association with complications. Strict application of protocols could
      decrease the risk for complications and boost nutritional support benefits.

PMID- 24893057
TI  - Analysis of population genetic structure from Bucaramanga (Colombia) based on
      gene polymorphisms associated with the regulation of blood pressure.
AB  - INTRODUCTION: In spite of nearly 40% of variability in blood pressure being
      explained by genetic factors, the identification of genes associated with
      essential high blood pressure is difficult to determine in populations where
      individuals have different genetic backgrounds. In these circumstances it is
      necessary to determinate whether the population is sub-structured because this
      can bias studies associated with this disease. OBJECTIVE: TO DETERMINE THE
      GENETIC STRUCTURE OF THE POPULATION IN BUCARAMANGA FROM GENETIC POLYMORPHISMS
      ASSOCIATED WITH THE REGULATION OF BLOOD PRESSURE: 448G>T, 679C>T y 1711C>T from
      the gene kinase 4 of the dopaminergic receptor linked to the protein G and
      Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric
      oxide. METHODS: A sample of 552 unrelated individuals was studied through
      analysis of restriction fragment length polymorphism. The allelic, haplotypic and
      genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was
      determined and a molecular analysis of variance was performed to determine the
      genetic structure. RESULTS: Thirty-eight (38) Haplotypes were identified with
      GCCTG4b being the most frequent (21.2%). The most diverse polymorphism was 448G>T
      with a frequency of 49.9% for heterozygous. The six polymorphisms were found in
      genetic equilibrium and a genetic structure of populations was not evidenced
      (FST= 0.0038). CONCLUSION: The population studied does not present a genetic sub
      structure and the polymorphisms analyzed were found in genetic equilibrium. This
      indicates that the population mixes randomly and there are no sub-groups capable
      of affecting the results of the association studies.

PMID- 24893058
TI  - Intracystic papillary breast carcinoma with areas of infiltration : Report on two
      cases.
AB  - Intracystic papillary carcinoma of the breast associated with areas of
      infiltration is rare in that it constitutes less than 1% of breast cancers. After
      initial radiological study, these tumors show lesions with little likelihood of
      malignancy in a high proportion of cases. Two cases of intracystic papillary
      carcinoma associated with infiltration were diagnosed at the Breast Unit of
      Hospital Infanta Cristina. In both cases, the reason for consultation arose after
      palpation of a nodule and the initial radiographic analyses showed lesions with
      little likelihood of malignancy. 

PMID- 24893059
TI  - Coping and adaptation process during puerperium.
AB  - INTRODUCTION: The puerperium is a stage that produces changes and adaptations in
      women, couples and family. Effective coping, during this stage, depends on the
      relationship between the demands of stressful or difficult situations and the
      recourses that the puerperal individual has. Roy (2004), in her Middle Range
      Theory about the Coping and Adaptation Processing, defines Coping as the
      ''behavioral and cognitive efforts that a person makes to meet the environment
      demands''. For the puerperal individual, the correct coping is necessary to
      maintain her physical and mental well being, especially against situations that
      can be stressful like breastfeeding and return to work. According to Lazarus and
      Folkman (1986), a resource for coping is to have someone who receives emotional
      support, informative and / or tangible. OBJECTIVE: To review the issue of women
      coping and adaptation during the puerperium stage and the strategies that enhance
      this adaptation. METHODS: SEARCH AND SELECTION OF DATABASE ARTICLES: Cochrane,
      Medline, Ovid, ProQuest, Scielo, and Blackwell Synergy. Other sources:
      unpublished documents by Roy, published books on Roy's Model, Websites from of
      international health organizations. RESULTS: the need to recognize the puerperium
      as a stage that requires comprehensive care is evident, where nurses must be
      protagonist with the care offered to women and their families, considering the
      specific demands of this situation and recourses that promote effective coping
      and the family, education and health services.

PMID- 24893060
TI  - Murine Typhus: Clinical and epidemiological aspects.
AB  - RICKETTSIA TYPHI: is an intracellular bacteria who causes murine typhus. His
      importance is reflected in the high frequency founding specific antibodies
      against Rickettsia typhi in several worldwide seroepidemiological studies, the
      seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats
      (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his
      vector. This infection is associated with overcrowding, pollution and poor
      hygiene. Typically presents fever, headache, rash on trunk and extremities, in
      some cases may occur organ-specific complications, affecting liver, kidney, lung
      or brain. Initially the disease is very similar to other diseases, is very common
      to confuse the murine typhus with Dengue fever, therefore, ignorance of the
      disease is a factor related to complications or non-specific treatments for the
      resolution of this infection. This paper presents the most relevant information
      to consider about the rickettsiosis caused by Rickettsia typhi.

PMID- 24893061
TI  - Should we stop using the determination of central venous pressure as a way to
      estimate cardiac preload?
AB  - INTRODUCTION: The determination of the values of central venous pressure has long
      been used as a guideline for volumetric therapy in the resuscitation of the
      critical patient, but the performance of such parameter is currently being
      questioned as an effective measurement of cardiac preload. This has aroused great
      interest in the search for more accurate parameters to determine cardiac preload
      and a patient's blood volume. GOALS AND METHODS: Based on literature currently
      available, we aim to discuss the performance of central venous pressure as an
      effective parameter to determine cardiac preload. RESULTS AND CONCLUSION:
      Estimating variables such as end-diastolic ventricular area and global end
      diastolic volume have a better performance than central venous pressure in
      determining cardiac preload. Despite the best performance of these devices,
      central venous pressure is still considered in our setting as the most practical
      and most commonly available way to assess the patient's preload. Only dynamic
      variables such as pulse pressure change are superior in determining an
      individual's blood volume.

PMID- 24893062
TI  - The fiction of health Services.
AB  - What we know today as Health Services is a fiction, perhaps shaped involuntarily,
      but with deep health repercussions, more negative than positive. About 24
      centuries ago, Asclepius, god of medicine, and Hygeia, goddess of hygiene and
      health, generated a dichotomy between disease and health that remains with us
      until today. The confusing substitution of Health Services with Medical Services
      began toward the end of the XIX century. But it was in 1948 when the so called
      English National Health Service became a landmark in the world with its model
      being adopted by many countries with resulting distortion of the true meaning of
      Health Services. The consequences of this fiction have been ominous. It is
      necessary to call things by their names and not deceive society. To correct the
      serious imbalance between Medical Services and Health Services, Hygeia and
      Asclepius must become a brother and sisterhood. 

PMID- 24893063
TI  - Dehydroergosterol as an analogue for cholesterol: why it mimics cholesterol so
      well-or does it?
AB  - Although dehydroergosterol (DHE) is one of the most commonly used cholesterol
      (CHOL) reporters, it has remained unclear why it performs well compared with most
      other CHOL analogues and what its possible limitations are. We present a
      comprehensive study of the properties of DHE using a combination of time-resolved
      fluorescence spectroscopy, quantum-mechanical electronic structure computations,
      and classical atomistic molecular dynamics simulations. We first establish that
      DHE mimics CHOL behavior, as previous studies have suggested, and then move on to
      elucidate and discuss the particular properties that render DHE so superior. We
      found that the main reason why DHE mimics CHOL so well is due to its ability to
      stand upright in a membrane in a manner that is almost identical to that of CHOL.
      The minor difference in how DHE and CHOL tilt with respect to membrane normal has
      only faint effects on structural membrane properties, and even the lateral
      pressure profiles of model membranes with CHOL or DHE are almost identical. These
      results suggest that the mechanical/elastic effects of DHE on the function of
      mechanically sensitive membrane proteins are not substantially different from
      those of CHOL. Our study highlights similar dynamical behavior of CHOL and DHE,
      which implies that DHE can mimic CHOL in processes with free energies close to
      the thermal energy. 

PMID- 24893064
TI  - Can we predict burnout severity from empathy-related brain activity?
AB  - Empathy cultivates deeper interpersonal relationships and is important for
      socialization. However, frequent exposure to emotionally-demanding situations may
      put people at risk for burnout. Burnout has become a pervasive problem among
      medical professionals because occupational burnout may be highly sensitive to
      empathy levels. To better understand empathy-induced burnout among medical
      professionals, exploring the relationship between burnout severity and strength
      of empathy-related brain activity may be key. However, to our knowledge, this
      relationship has not yet been explored. We studied the relationship between self
      reported burnout severity scores and psychological measures of empathic
      disposition, emotional dissonance and alexithymia in medical professionals to
      test two contradictory hypotheses: Burnout is explained by (1) 'compassion
      fatigue'; that is, individuals become emotionally over involved; and (2)
      'emotional dissonance'; that is, a gap between felt and expressed emotion,
      together with reduced emotional regulation. Then, we tested whether increased or
      decreased empathy-related brain activity measured by fMRI was associated with
      burnout severity scores and psychological measures. The results showed that
      burnout severity of medical professionals is explained by 'reduced' empathy
      related brain activity. Moreover, this reduced brain activity is correlated with
      stronger emotional dissonance and alexithymia scores and also greater empathic
      disposition. We speculate that reduced emotion recognition (that is, alexithymia)
      might potentially link with stronger emotional dissonance and greater burnout
      severity alongside empathy-related brain activity. In this view, greater empathic
      disposition in individuals with higher burnout levels might be due to greater
      difficulty identifying their own emotional reactions. Our study sheds new light
      on the ability to predict empathy-induced burnout. 

PMID- 24893067
TI  - Overexpression of p53 in the endometrial gland in postmenopausal women.
AB  - OBJECTIVE: The p53 signature, which (although morphologically unremarkable)
      displays diffuse and strong p53 nuclear staining, has been proposed to be a
      precursor of serous endometrial intraepithelial carcinoma. We examined the
      overexpression of p53 in postmenopausal endometrial glands. METHODS:
      Postmenopausal endometrial tissues of 82 women with benign disease, including 10
      hormone users, were evaluated in this study. Tissues with endometrial hyperplasia
      and/or polyps were excluded based on a histopathologic review. Expressions of
      estrogen receptor-alpha, Ki-67, and p53 were immunohistochemically examined.
      Apoptotic cells were identified using a terminal deoxynucleotidyl transferase
      dUTP nick end labeling assay. Overexpression of p53 was categorized as moderate
      to strong in more than 50% of glandular cell nuclei. RESULTS: Focal glandular
      overexpression of p53 was observed in 1 (9%) of 10 and in 8 (11%) of 72
      postmenopausal endometrial tissue specimens in women with and women without a
      history of hormone use, respectively. Among nonhormone users, the median Ki-67
      and apoptotic indices in the postmenopausal endometrial glands of women with and
      women without overexpression of p53 were 16% and 6% (P = 0.007) and 1% and 1% (P
      = 0.345), respectively. All postmenopausal endometrial glands were positive for
      estrogen receptor-alpha, regardless of the overexpression of p53. The
      postmenopausal endometrial glands of estrogen users exhibited significantly
      higher Ki-67 and apoptotic indices than those of nonestrogen users (P = 0.001 and
      P < 0.001, respectively). CONCLUSIONS: Overexpression of p53 may be responsible
      for the high proliferative activity of postmenopausal endometrial glandular cells
      associated with conditions of low apoptotic cell death.

PMID- 24893065
TI  - Towards a molecular characterization of autism spectrum disorders: an exome
      sequencing and systems approach.
AB  - The hypothetical 'AXAS' gene network model that profiles functional patterns of
      heterogeneous DNA variants overrepresented in autism spectrum disorder (ASD), X
      linked intellectual disability, attention deficit and hyperactivity disorder and
      schizophrenia was used in this current study to analyze whole exome sequencing
      data from an Australian ASD cohort. An optimized DNA variant filtering pipeline
      was used to identify loss-of-function DNA variations. Inherited variants from
      parents with a broader autism phenotype and de novo variants were found to be
      significantly associated with ASD. Gene ontology analysis revealed that putative
      rare causal variants cluster in key neurobiological processes and are
      overrepresented in functions involving neuronal development, signal transduction
      and synapse development including the neurexin trans-synaptic complex. We also
      show how a complex gene network model can be used to fine map combinations of
      inherited and de novo variations in families with ASD that converge in the L1CAM
      pathway. Our results provide an important step forward in the molecular
      characterization of ASD with potential for developing a tool to analyze the
      pathogenesis of individual affected families. 

PMID- 24893068
TI  - Effect of the alkyl chain length of secondary amines on the phase transfer of
      gold nanoparticles from water to toluene.
AB  - In the present paper we describe a phase transfer of aqueous synthesized gold
      nanoparticles (AuNPs) from water to toluene using secondary amines: dioctylamine,
      didodecylamine, and dioctadecylamine. The effect of the hydrocarbon chain length
      and amount of amines on the transfer efficiency were investigated in the case of
      nanoparticles (NPs) with three different sizes: 5, 9, and 13 nm. Aqueous colloids
      were precisely characterized before the transfer process using UV-vis
      spectroscopy, dynamic light scattering (DLS), small-angle X-ray scattering
      (SAXS), and transmission electron microscopy (TEM). Nanoparticles were next
      transferred to toluene and characterized using UV-vis and DLS techniques. It was
      found that dioctadecylamine provides the most effective transfer of
      nanoparticles. No time-dependent changes in the NP size were observed after 12
      days, showing that the dioctadecylamine-stabilized nanoparticles dispersed in
      toluene were stable. This indicates that long hydrocarbon chains of
      dioctadecylamine exhibit sufficiently hydrophobic properties of nanoparticles and
      consequently their good dispersibility in nonpolar solvent. 

PMID- 24893066
TI  - NMDA receptor antagonists ketamine and Ro25-6981 inhibit evoked release of
      glutamate in vivo in the subiculum.
AB  - Preclinical and clinical data have identified ketamine, a non-selective NMDAR (N
      methyl-D-aspartate receptor) antagonist, as a promising medication for patients
      who do not respond to treatment with monoamine-based antidepressants. Moreover,
      unlike the current monoamine-based antidepressants, ketamine has a long-lasting
      effect already after a single dose. The mechanisms of ketamine action remain to
      be fully understood. Using a recently developed microelectrode array (MEA), which
      allows sub-second measurements of fluctuating glutamate concentrations, we
      studied here the effects of in vivo local application of the ketamine and of the
      N2B subunit-specific antagonist Ro25-6981 upon evoked glutamate release. Both
      ligands inhibit glutamate release in subregions of the hippocampus and prefrontal
      cortex. Likewise, acute systemic ketamine treatment, at an antidepressant dose,
      caused a reduction in evoked glutamate release in the subiculum. We suggest that
      the effects of ketamine and Ro25-6981 in the subiculum could involve blockade of
      presynaptic NMDA receptors containing N2B subunits. 

PMID- 24893070
TI  - Tetranuclear silver(I) clusters showing high ionic conductivity in a bicontinuous
      cubic mesophase.
AB  - The synthesis and characterization of tetranuclear silver triazole
      metallomesogens, [Ag4(L(4)-C(n))6][BF4]4 (L(4)-C(n) = 4-alkyl-1,2,4-triazoles
      where C(n) stands for C(n)H(2n+1) with n = 12, 14, 16, and 18), are reported.
      Upon heating, a phase transition sequence of Cr -> SmC -> Cub -> SmA -> isotropic
      liquid is observed for all of these compounds. Depending on the alkyl chain
      length, two types of cubic phases are found in this series of compounds. Those
      with shorter alkyl chains (n = 12 and 14) exhibit a micellar cubic phase, whereas
      long alkyl chains (n =16 and 18) show a bicontinuous cubic phase. Superior ionic
      conductivity at the bicontinuous cubic mesophase for [Ag4(L4-C16)6][BF4]4 is
      observed because of the presence of a three-dimensional ion-transporting channel.
      Doping a small amount of AgBF4 enhances the ionic conduction dramatically,
      presumably via promotion of the migration of Ag(I) ions in the channels.

PMID- 24893073
TI  - Vegetable dinner: Peter Blume.

PMID- 24893069
TI  - General method for functionalized polyaryl synthesis via aryne intermediates.
AB  - A method for base-promoted arylation of arenes and heterocycles by aryl halides
      and aryl triflates is described. Additionally, in situ electrophilic trapping of
      ArLi intermediates generated in the reaction of benzyne with deprotonated arenes
      or heterocycles has been developed, providing rapid and easy access to a wide
      range of highly functionalized polyaryls. Base-promoted arylation methodology
      complements transition-metal-catalyzed direct arylation and allows access to
      structures that are not easily accessible via other direct arylation methods. The
      reactions are highly functional-group tolerant, with alkene, ether,
      dimethylamino, trifluoromethyl, ester, cyano, halide, hydroxyl, and silyl
      functionalities compatible with reaction conditions. 

PMID- 24893074
TI  - First US MERS-CoV cases underscore need for preparedness.

PMID- 24893084
TI  - Studying the elusive environment in large scale.

PMID- 24893085
TI  - A piece of my mind. The $50,000 physical.

PMID- 24893086
TI  - Editorial matters: guidelines for writing effective editorials.

PMID- 24893089
TI  - Resistant hypertension: a review of diagnosis and management.
AB  - Resistant hypertension-uncontrolled hypertension with 3 or more antihypertensive
      agents-is increasingly common in clinical practice. Clinicians should exclude
      pseudoresistant hypertension, which results from nonadherence to medications or
      from elevated blood pressure related to the white coat syndrome. In patients with
      truly resistant hypertension, thiazide diuretics, particularly chlorthalidone,
      should be considered as one of the initial agents. The other 2 agents should
      include calcium channel blockers and angiotensin-converting enzyme inhibitors for
      cardiovascular protection. An increasing body of evidence has suggested benefits
      of mineralocorticoid receptor antagonists, such as eplerenone and spironolactone,
      in improving blood pressure control in patients with resistant hypertension,
      regardless of circulating aldosterone levels. Thus, this class of drugs should be
      considered for patients whose blood pressure remains elevated after treatment
      with a 3-drug regimen to maximal or near maximal doses. Resistant hypertension
      may be associated with secondary causes of hypertension including obstructive
      sleep apnea or primary aldosteronism. Treating these disorders can significantly
      improve blood pressure beyond medical therapy alone. The role of device therapy
      for treating the typical patient with resistant hypertension remains unclear. 

PMID- 24893087
TI  - Association of azithromycin with mortality and cardiovascular events among older
      patients hospitalized with pneumonia.
AB  - IMPORTANCE: Although clinical practice guidelines recommend combination therapy
      with macrolides, including azithromycin, as first-line therapy for patients
      hospitalized with pneumonia, recent research suggests that azithromycin may be
      associated with increased cardiovascular events. OBJECTIVE: To examine the
      association of azithromycin use with all-cause mortality and cardiovascular
      events for patients hospitalized with pneumonia. DESIGN: Retrospective cohort
      study comparing older patients hospitalized with pneumonia from fiscal years 2002
      through 2012 prescribed azithromycin therapy and patients receiving other
      guideline-concordant antibiotic therapy. SETTING: This study was conducted using
      national Department of Veterans Affairs administrative data of patients
      hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS:
      Patients were included if they were aged 65 years or older, were hospitalized
      with pneumonia, and received antibiotic therapy concordant with national clinical
      practice guidelines. MAIN OUTCOMES AND MEASURES: Outcomes included 30- and 90-day
      all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial
      infarction, and any cardiac event. Propensity score matching was used to control
      for the possible effects of known confounders with conditional logistic
      regression. RESULTS: Of 73,690 patients from 118 hospitals identified, propensity
      matched groups were composed of 31,863 patients exposed to azithromycin and
      31,863 matched patients who were not exposed. There were no significant
      differences in potential confounders between groups after matching. Ninety-day
      mortality was significantly lower in those who received azithromycin (exposed,
      17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However,
      we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR,
      1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95%
      CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95
      1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04).
      CONCLUSIONS AND RELEVANCE: Among older patients hospitalized with pneumonia,
      treatment that included azithromycin compared with other antibiotics was
      associated with a lower risk of 90-day mortality and a smaller increased risk of
      myocardial infarction. These findings are consistent with a net benefit
      associated with azithromycin use.

PMID- 24893090
TI  - Prophylactic antibiotic therapy in chronic obstructive pulmonary disease.
AB  - CLINICAL QUESTION Is prophylactic antibiotic treatment associated with fewer
      exacerbations or improved health-related quality of life (HRQOL) in patients with
      chronic obstructive pulmonary disease (COPD)? BOTTOM LINE Continuous macrolide
      antibiotic use for prophylaxis was associated with a clinically significant
      reduction in COPD exacerbations. Pulsed antibiotic use was not associated with
      benefit. Continuous and pulsed antibiotics were associated with improved HRQOL,
      but this was not clinically significant. 

PMID- 24893091
TI  - Progressive anemia and left upper quadrant pain in a patient with polycythemia
      vera.

PMID- 24893088
TI  - Association between prophylactic implantable cardioverter-defibrillators and
      survival in patients with left ventricular ejection fraction between 30% and 35%.
AB  - IMPORTANCE: Clinical trials of prophylactic implantable cardioverter
      defibrillators (ICDs) have included a minority of patients with a left
      ventricular ejection fraction (LVEF) between 30% and 35%. Because a large number
      of ICDs in the United States are implanted in such patients, it is important to
      study survival associated with this therapy. OBJECTIVE: To characterize patients
      with LVEF between 30% and 35% and compare the survival of those with and without
      ICDs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of Medicare
      beneficiaries in the National Cardiovascular Data Registry ICD registry (January
      1, 2006, through December 31, 2007) with an LVEF between 30% and 35% who received
      an ICD during a heart failure hospitalization and similar patients in the Get
      With The Guidelines-Heart Failure (GWTG-HF) database (January 1, 2005, through
      December 31, 2009) with no ICD. The analysis was repeated in patients with an
      LVEF less than 30%. There were 3120 patients with an LVEF between 30% and 35%
      (816 in matched cohorts) and 4578 with an LVEF less than 30% (2176 in matched
      cohorts). Propensity score matching and Cox models were applied. MAIN OUTCOMES
      AND MEASURES: The primary outcome was all-cause mortality; data were obtained
      from Medicare claims through December 31, 2011. RESULTS: There were no
      significant differences in the baseline characteristics of the matched groups (n
      = 408 for both groups). Among patients with an LVEF between 30% and 35%, there
      were 248 deaths in the ICD Registry group, within a median follow-up of 4.4 years
      (interquartile range, 2.7-4.9) and 249 deaths in the GWTG HF group, within a
      median follow-up of 2.9 years (interquartile range, 2.1-4.4). The risk of all
      cause mortality in patients with an LVEF between 30% and 35% and an ICD was
      significantly lower than that in matched patients without an ICD (3-year
      mortality rates: 51.4% vs 55.0%; hazard ratio, 0.83 [95% CI, 0.69-0.99]; P =
      .04). Presence of an ICD also was associated with better survival in patients
      with an LVEF less than 30% (3-year mortality rates: 45.0% vs 57.6%; 634 and 660
      total deaths; hazard ratio, 0.72 [95% CI, 0.65-0.81]; P < .001) (P = .20 for
      interaction). CONCLUSIONS AND RELEVANCE: Among Medicare beneficiaries
      hospitalized for heart failure and with an LVEF between 30% and 35% and less than
      30%, survival at 3 years was better in patients who received a prophylactic ICD
      than in comparable patients with no ICD. These findings support guideline
      recommendations to implant prophylactic ICDs in eligible patients with an LVEF of
      35% or less.

PMID- 24893092
TI  - Salt restriction.

PMID- 24893093
TI  - Recurrence and mortality following severe cutaneous adverse reactions.

PMID- 24893094
TI  - Prehospital therapeutic hypothermia in patients with out-of-hospital cardiac
      arrest.

PMID- 24893095
TI  - Prehospital therapeutic hypothermia in patients with out-of-hospital cardiac
      arrest--reply.

PMID- 24893096
TI  - Cardiopulmonary resuscitation with mechanical chest compressions and simultaneous
      defibrillation.

PMID- 24893097
TI  - Cardiopulmonary resuscitation with mechanical chest compressions and simultaneous
      defibrillation--reply.

PMID- 24893098
TI  - Guidelines for cardiovascular risk assessment and cholesterol treatment.

PMID- 24893099
TI  - Guidelines for cardiovascular risk assessment and cholesterol treatment--reply.

PMID- 24893100
TI  - Guidelines for cardiovascular risk assessment and cholesterol treatment--reply.

PMID- 24893102
TI  - The rational treatment of arterial hypertension.

PMID- 24893103
TI  - JAMA patient page. Hospital medicine and hospitalists.

PMID- 24893104
TI  - Editorial explaining the change in name of this journal to Journal of
      Experimental Psychology: Animal Learning and Cognition.
AB  - This editorial explains the reasoning behind The Journal of Experimental
      Psychology: Animal Behavior Processes name change. This Journal started
      publication in 1975 as a result of a major reorganization of the American
      Psychological Association's basic science journals. To signal that expansion of
      interest, the name of the journal has been changed to Journal of Experimental
      Psychology: Animal Learning and Cognition. This change is not meant to discourage
      submission of the types of manuscripts that have most frequently appeared in the
      journal in recent years but to encourage submission of papers across a broader
      range of topics.

PMID- 24893105
TI  - Suboptimal choice by pigeons may result from the diminishing effect of
      nonreinforcement.
AB  - Pigeons prefer an alternative that provides them with a stimulus 20% of the time
      that predicts 10 pellets of food and a different stimulus 80% of the time that
      predicts 0 pellets, over an alternative that provides them with a stimulus that
      always predicts 3 pellets of food, even though the preferred alternative provides
      them with considerably less food. It appears that the stimulus that predicts 10
      pellets acts as a strong conditioned reinforcer, despite the fact that the
      stimulus that predicts 0 pellets occurs 4 times as often. In the present
      research, we tested the hypothesis that early in training conditioned inhibition
      develops to the 0-pellet stimulus, but later in training it dissipates. We
      trained pigeons with a hue as the 10-pellet stimulus and a vertical line as the 0
      pellet stimulus. To assess the inhibitory value of the vertical line, we compared
      responding to the 10-pellet hue with responding to the compound of the 10-pellet
      hue and the vertical line early in training and once again late in training,
      using both a within-subject design (Experiment 1) and a between-groups design
      (Experiment 2). We found that there was a significant reduction in inhibition
      between the early test (when pigeons chose optimally) and late test (when choice
      was suboptimal). Thus, the increase in suboptimal choice may result from the
      decline in inhibition to the 0-pellet stimulus. Implications for human gambling
      behavior are considered.

PMID- 24893107
TI  - Persistence in extinction: the sunk time effect.
AB  - We investigated the sunk time effect, persistence in a nonpreferred option owing
      to prior investment of time in that option. Pigeons chose between two
      concurrently available keys-2 fixed-interval (FI) food requirements were arranged
      on 1 key, and an escape option, which terminated the current trial and started a
      new one, on a second key. One FI was longer than the other, and the shorter FI
      was always more probable on any given trial. In most conditions, the different FI
      schedules were not signaled. In this situation, the optimal behavior would be for
      pigeons to escape from the long FI once the duration equivalent to the short FI
      had elapsed without reinforcement. Several variables that could influence
      persistence or escape behavior were manipulated: the presence and absence of cues
      signaling the type of trial in effect (Experiments 1 and 2), extinction in the
      long interval (Experiments 3, 4, and 5), the intertrial-interval duration
      (Experiments 5 and 6), and the duration of the FI schedules (Experiments 1-6).
      Overall, the results showed that pigeons tend to persist and finish the current
      trial, even with extinction in the long interval, a result consistent with the
      sunk time effect.

PMID- 24893106
TI  - The effect of a prior investment on choice: the sunk cost effect.
AB  - We investigated the effect of prior investment on choice in pigeons, namely, the
      sunk cost effect, which is a tendency to continue an endeavor once a prior
      investment has been made, despite a better option being available. In a
      concurrent-chains procedure, pigeons chose between left and right keys in the
      choice phase leading to different work requirements in the outcome phase. Within
      each session, two components were signaled by red or green keys in the choice
      phase. Components were identical, except that in red components, the choice was
      preceded by a prior investment of 20 pecks on the left key, whereas in green
      components, the investment of 20 pecks was on the right key. Preference for the
      key with the prior investment was studied in a series of experiments in which we
      manipulated the absence or presence of the investment (Experiments 1a and 1b) and
      size of the investment (Experiments 2 and 3). We also investigated whether the
      bias observed was a result of carryover effects or of the sunk cost effect
      (Experiment 4). Overall, the results showed that choice was biased toward the
      alternative associated with the prior investment, consistent with the sunk cost
      effect, an effect that can be understood in terms of within-trial contrast and
      the delay-reduction hypothesis.

PMID- 24893108
TI  - I like to get nothing: implicit and explicit evaluation of avoided negative
      outcomes.
AB  - This study examined affective consequences of an active avoidance response.
      Catching a fleeting stimulus with a rapid key press secured a monetary reward in
      a reward condition or avoided a monetary loss in an avoidance condition. Outcomes
      of wins, missed wins, losses, and avoided losses were signaled with color patches
      that were evaluated explicitly (via evaluative rating) and implicitly (via an
      affective priming task). Liking scores in each condition were compared with those
      in yoked-control conditions in which wins and avoided losses were presented
      without the requirement of an active response. In the explicit measure, colors
      associated with an avoided loss were rated positively and colors associated with
      a missed win were judged negatively, irrespective of whether the outcome was self
      generated. In the implicit measure, outcomes of missed wins and avoided losses
      were evaluated differently only when they were self-generated. The results
      confirm a qualitative affective equivalence between an avoided loss and an
      achieved win. Implications for avoidance theories are discussed.

PMID- 24893109
TI  - Comparative transcriptional activity of five promoters in BAC-cloned MDV for the
      expression of the hemagglutinin gene of H9N2 avian influenza virus.
AB  - On the basis of recent studies, much attention has been given to recombinant MDV
      (rMDV)-based vaccines. During the construction of rMDV, the activity of promoters
      to transcribe foreign genes is one of the major factors that can affect
      protective efficacy. To investigate the transcription activity and efficacy of
      five different promoters, the advantage of an existing rMDV BAC infectious clone
      that had been previously constructed was used to construct rMDVs. The expression
      cassette of the hemagglutinin gene (HA) from a low pathogenic avian influenza
      virus (LPAIV) H9N2 strain was inserted into the US2 region under five selected
      promoters. These five promoters included three MDV endogenous promoters (the
      promoter for the gB gene and a bi-directional promoter in both directions for
      pp38 (ppp38) and 1.8 kb RNA transcripts (p1.8 kb)), and two exogenous promoters
      (CMV and SV40). Among these five promoters, the CMV promoter demonstrated the
      highest activity, followed by p1.8 kb and SV40, which had a similar
      transcriptional activity level. Two of the MDV endogenous promoters showed much
      lower transcriptional activities, particularly the promoter ppp38, which had the
      lowest activity. The results of the in vivo experiment proved that none of the
      three recombinant viruses of rGX-CMV-HA, rGX-SV40-HA and rGX-p1.8kb-HA provided
      protection in SPF chickens. Chickens vaccinated with rGX-pPP38-HA induced 50% and
      rGX-gB-HA induced 25% protection against the challenge with H9N2, respectively.

PMID- 24893111
TI  - The inverse relationship between food price and energy density: is it spurious?
AB  - OBJECTIVE: An important debate in the literature is whether or not higher energy
      dense foods are cheaper than less energy-dense foods. The present communication
      develops and applies an easy statistical test to determine if the relationship
      between food price and energy density is an artifact of how the data units are
      constructed (i.e. is it 'spurious' or 'real'?). DESIGN: After matching data on
      4430 different foods from the National Health and Nutrition Examination Survey
      with corresponding prices from the Center for Nutrition Policy and Promotion's
      Food Prices Database, we use a simple regression model to test if the
      relationship between food price and energy density is 'real' or 'spurious'.
      SETTING: USA. SUBJECTS: Total sample size is 4430 observations of consumed foods
      from 4578 participants from the non-institutionalized US adult population (aged
      19 years and over). RESULTS: Over all 4430 foods, the null hypothesis of a
      spurious inverse relationship between food price per energy density and energy
      density is not rejected. When the analysis is broken down by twenty-five food
      groups, there are only two cases where the inverse relationship is not spurious.
      In fact, the majority of non-spurious relationships between food price and energy
      density are positive, not negative. CONCLUSIONS: One of the main arguments put
      forth regarding the poor diet quality of low-income households is that high
      energy-dense food is cheaper than lower energy-dense food. We find almost no
      statistical support for higher energy-dense food being cheaper than low energy
      dense food. While economics certainly plays a role in explaining low nutritional
      quality, more sophisticated economic arguments are required and discussed.

PMID- 24893110
TI  - In vitro inhibition of Cyprinid herpesvirus-3 replication by RNAi.
AB  - Cyprinid herpesvirus-3 (CyHV-3) is an etiological agent of a notifiable disease
      that causes high mortality rates affecting both the common and koi carp Cyprinus
      carpio L. There is no current treatment strategy to save CyHV-3 infected fish.
      RNA mediated interference (RNAi) is an emerging strategy used for understanding
      gene function and is a promising method in developing novel therapeutics and
      antiviral medications. For this study, the possibility of activating the RNAi
      pathway by the use of small interfering (si)RNAs was tested to inhibit in vitro
      viral replication of CyHV-3 in common carp brain (CCB) cells. The siRNAs were
      designed to target either thymidine kinase (TK) or DNA polymerase (DP) genes,
      which both code for transcripts involved in DNA replication. The inhibition of
      viral replication caused by the siRNAs was measured by a reporter gene, termed
      ORF81. Treatment with siRNA targeting either TK or DP genes reduced the release
      of viral particles from infected CCB cells. However, siRNA targeting DP was most
      effective at reducing viral release as measured by qPCR. 

PMID- 24893113
TI  - Providing information promotes greater public support for potable recycled water.
AB  - In spite of the clear need to address water security through sourcing new and
      alternative water supplies, there has been marked resistance from some
      communities to the introduction of recycled water for potable use. The present
      studies tested the effectiveness of providing relatively brief information about
      the recycled water process and the safety of recycled water on cognitive,
      emotional and behavioral responses. Three information conditions (basic
      information or basic information plus information about pollutants in the water,
      or information that puts the risk of chemicals in the water in perspective) were
      compared to a no information control condition. Across three experiments there
      was general support for the hypothesis that providing information would result in
      more positive cognitive, emotional, and behavioral responses to recycled water.
      Information increased comfort with potable recycled water and, in general,
      participants in the information conditions expressed more positive emotions
      (Experiment 1 & 3), less negative emotions (Experiment 3), more support
      (Experiment 1 & 3), and lower risk perceptions (Experiment 1 & 3) than those in
      the no information control condition. Participants who received information also
      drank more recycled water than control participants (Experiment 1 & 2, although
      the differences between conditions was not statistically significant) and were
      significantly more likely to vote in favor of the introduction of a recycled
      water scheme (Experiment 3). There was evidence, however, that providing
      information about the level of pollutants in recycled water may lead to
      ambivalent responses. 

PMID- 24893114
TI  - Sparse deconvolution in one and two dimensions: applications in endocrinology and
      single-molecule fluorescence imaging.
AB  - Deconvolution of noisy signals is an important task in analytical chemistry,
      examples being spectral deconvolution or deconvolution in microscopy. When the
      number of spectral peaks or single emitters in imaging is limited, the solution
      of the deconvolution is required to be sparse, and desirable results are obtained
      using a penalized estimation techniques. We impose sparseness by using penalized
      regression with a penalty based on the L0-norm, as discussed in earlier work.
      Several extensions to this approach are presented. Results are demonstrated on
      pulse identification in endocrine data where the aim is to model the secretion
      pattern as a sparse series of spikes. An application in single-molecule
      fluorescence imaging demonstrates the algorithm when applied to two-dimensional
      data. 

PMID- 24893112
TI  - Ufmylation and FATylation pathways are downregulated in human alcoholic and
      nonalcoholic steatohepatitis, and mice fed DDC, where Mallory-Denk bodies (MDBs)
      form.
AB  - We previously reported the mechanisms involved in the formation of Mallory-Denk
      bodies (MDBs) in mice fed DDC. To further provide clinical evidence as to how
      ubiquitin-like protein (Ubls) modification, gene transcript expression in
      Ufmylation and FATylation were investigated in human archived formalin-fixed,
      paraffin-embedded (FFPE) liver biopsies and frozen liver sections from DDC re-fed
      mice were used. Real-time PCR analysis showed that all Ufmylation molecules
      (Ufm1, Uba5, Ufc1, Ufl1 and UfSPs) were significantly downregulated, both in DDC
      re-fed mice livers and patients' livers where MDBs had formed, indicating that
      gene transcript changes were limited to MDB-forming livers where the protein
      quality control system was downregulated. FAT10 and subunits of the
      immunoproteasome (LMP2 and LMP7) were both upregulated as previously shown. An
      approximate 176- and 5-fold upregulation (respectively) of FAT10 was observed in
      the DDC re-fed mice liver and in the livers of human alcoholic hepatitis with
      MDBs present, implying that there was an important role played by this gene. The
      FAT10-specific E1 and E2 enzymes Uba6 and USE1, however, were found to be
      downregulated both in patients' livers and in the liver of DDC re-fed mice.
      Interestedly, the downregulation of mRNA levels was proportionate to MDB
      abundance in the liver tissues. Our results show the first systematic
      demonstration of transcript regulation of Ufmylation and FATylation in the liver
      of patients who form MDBs, where protein quality control is downregulated. This
      was also shown in the livers of DDC re-fed mice where MDBs had formed. 

PMID- 24893115
TI  - Phase-coexistence and thermal hysteresis in samples comprising adventitiously
      doped MnAs nanocrystals: programming of aggregate properties in magnetostructural
      nanomaterials.
AB  - Small changes in the synthesis of MnAs nanoparticles lead to materials with
      distinct behavior. Samples prepared by slow heating to 523 K (type-A) exhibit the
      characteristic magnetostructural transition from the ferromagnetic hexagonal
      (alpha) to the paramagnetic orthorhombic (beta) phase of bulk MnAs at Tp = 312 K,
      whereas those prepared by rapid nucleation at 603 K (type-B) adopt the beta
      structure at room temperature and exhibit anomalous magnetic properties. The
      behavior of type-B nanoparticles is due to P-incorporation (up to 3%), attributed
      to reaction of the solvent (trioctylphosphine oxide). P-incorporation results in
      a decrease in the unit cell volume (~1%) and shifts Tp below room temperature.
      Temperature-dependent X-ray diffraction reveals a large region of phase
      coexistence, up to 90 K, which may reflect small differences in Tp from particle
      to-particle within the nearly monodisperse sample. The large coexistence range
      coupled to the thermal hysteresis results in process-dependent phase mixtures. As
      prepared type-B samples exhibiting the beta structure at room temperature convert
      to a mixture of alpha and beta after the sample has been cooled to 77 K and
      rewarmed to room temperature. This change is reflected in the magnetic response,
      which shows an increased moment and a shift in the temperature hysteresis loop
      after cooling. The proportion of alpha present at room temperature can also be
      augmented by application of an external magnetic field. Both doped (type-B) and
      undoped (type-A) MnAs nanoparticles show significant thermal hysteresis narrowing
      relative to their bulk phases, suggesting that formation of nanoparticles may be
      an effective method to reduce thermal losses in magnetic refrigeration
      applications. 

PMID- 24893116
TI  - FTY720 attenuates paraquat-induced lung injury in mice.
AB  - Paraquat (PQ) poisoning, with the lung as a primary target organ, is a
      devastating disease which irreversibly progresses to diffuse alveolitis followed
      by extensive lung fibrosis. In the present study, we aimed to investigate the
      effect of FTY720, an immune modulator, on PQ-induced lung injury in mice. C57BL/6
      mice were randomized into four groups: 1) PQ group (n=12): mice was instilled
      with PQ (30 mg/kg, ip); 2) PQ+FTY720 group (n=12): animals received FTY720
      (0.1mg/kg, ip) solution 2h after PQ exposure and twice a week for 4 consecutive
      weeks; 3) FTY720 group (n=5): FTY720 (0.1mg/kg, ip) was administrated twice a
      week for 4 consecutive weeks; and 4) Control group (n=10): same volumes of saline
      were injected. Mice were sacrificed on either day 3 or day 28 for
      histopathological, biochemical and immunohistochemical analyses of lung damage
      indicators. We found that FTY720 treatment attenuated PQ-induced acute lung
      injury and lung fibrosis as evaluated by histopathological changes and Ashcroft
      score. On day 3, FTY720 administration reduced PQ-induced increases in lung wet
      weight/body weight (LW/BW), total protein and cytokine levels including
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) in bronchoalceolar lavage fluid (BALF). On day 28, the
      expressions of alpha-smooth muscle actin (alpha-SMA), transforming growth factor
      beta (TGF-beta) and vascular endothelial growth factor (VEGF) detected by
      immunohistochemistry, as well as the mRNA levels of alpha-SMA, Type-I Collagen
      and Type-III Collagen examined by Real-time PCR were down-regulated after FTY720
      treatment. These results indicate that FTY720 could attenuate PQ-induced lung
      injury, but further investigation is necessary.

PMID- 24893117
TI  - Diminazene aceturate (Berenil), a new use for an old compound?
AB  - Diminazene aceturate or Berenil has been the drug of choice for treatment of
      animal trypanosomiasis. Although the compound has been in the market since 1955,
      its mechanisms of action have remained poorly understood. While some earlier
      reports show that Berenil possesses trypanolytic and trypanostatic properties,
      some studies show it may also indirectly affect the host immune system. Our
      recent extensive studies show that treatment with Berenil reduces pro
      inflammatory cytokine (IL-6, IL-12 and TNF) production in macrophages in vivo and
      in vitro following stimulation with Trypanosoma congolense, lipopolysaccharide
      (LPS), unmethylated bacterial CpG motifs and Poly I:C. This global effect was not
      due to downregulation of Toll-like receptor (TLR) expression on innate immune
      cells. Instead, Berenil significantly downregulated phosphorylation of mitogen
      activated protein kinases (MAPKs, including ERK, p38 and JNK), signal transducer
      and activator of transcription (STAT) proteins (including STAT1 and STAT3) and
      NFkappaB p65 subunit, key signaling molecules and transcription factors involved
      in the production of proinflammatory cytokines. The ability of Berenil to
      downregulate major intracellular signaling pathways that lead to proinflammatory
      cytokine production suggests that it could be used to treat conditions caused by
      excessive production of inflammatory cytokines.

PMID- 24893119
TI  - Hydrogen transfer reaction in polycyclic aromatic hydrocarbon radicals.
AB  - Density functional theory calculations have been successfully applied to
      investigate the formation of hydrocarbon radicals and hydrogen transfer pathways
      related to the chemical vapor infiltration process based on model molecules of
      phenanthrene, anthra[2,1,9,8-opqra]tetracene, dibenzo[a,ghi]perylene,
      benzo[uv]naphtho[2,1,8,7-defg]pentaphene, and dibenzo[bc,ef]ovalene. The hydrogen
      transfer reaction rate constants are calculated within the framework of the Rice
      Ramsperger-Kassel-Marcus theory and the transition state theory by use of the
      density functional theory calculation results as input. From these calculations,
      it is concluded that the hydrogen transfer reaction between two bay sites can
      happen almost spontaneously with energy barrier as low as about 4.0 kcal mol(-1),
      and the hydrogen transfer reactions between two armchair sites possess lower
      energy barrier than those between two zigzag sites. 

PMID- 24893118
TI  - Efficient generation of highly immunocompetent dendritic cells from peripheral
      blood of patients with hepatitis C virus-related hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Immunotherapy using dendritic cells (DCs) is a promising
      cancer therapy. The success of this therapy depends on the function of induced
      DCs. However, there has been no consensus on optimal conditions for DC
      preparation in vitro for immunotherapy of hepatocellular carcinoma (HCC)
      patients. To address relevant issues, we evaluated the procedures to induce DCs
      that efficiently function in hepatitis C virus (HCV)-related HCC. METHODS: We
      studied immunological data from 14 HCC patients. The DC preparation and the
      surface markers were assessed by flow cytometric analysis. Four different
      additional activation stimuli (Method I, medium alone; Method II, with OK-432;
      Method III, with IL-1beta+IL-6+TNF-alpha; Method IV, with IL-1beta+IL-6+TNF
      alpha+PGE2) were tested and the functions of DCs were confirmed by examination of
      the ability of phagocytosis, cytokine production and allogeneic mixed lymphocyte
      reaction (MLR). RESULTS: The numbers of DCs induced and their cytokine production
      ability were not different between healthy controls and HCC patients. T-cell
      stimulatory activity of DCs in MLR was significantly lower in HCC patients than
      in healthy controls. The maturation of DCs with OK-432 boosted production of
      cytokines and chemokines, such as IL-2, IL-12p70, IFN-gamma, TNF-alpha, IL-13 and
      MIP1alpha, and restored T-cell stimulatory activity of DCs in MLR. CONCLUSIONS:
      The clinically approved compound OK-432 is a candidate for highly immunocompetent
      DC preparation and may be considered as a key drug for immunotherapy of HCV
      related HCC patients.

PMID- 24893121
TI  - Synthesis and crystal structure of new temephos analogues as cholinesterase
      inhibitor: molecular docking, QSAR study, and hydrogen bonding analysis of solid
      state.
AB  - A series of temephos (Tem) derivatives were synthesized and characterized by 31P,
      13C, and 1H NMR and FT-IR spectral techniques. Also, the crystal structure of
      compound 9 was investigated. The hydrogen bonding energies (E2) were calculated
      by NBO analysis of the crystal cluster. The activities and the mixed-type
      mechanism of Tem derivatives were evaluated using the modified Ellman's and
      Lineweaver-Burk's methods on cholinesterase (ChE) enzymes. The inhibitory
      activities of Tem derivatives with a P?S moiety were higher than those with a P?O
      moiety. Docking analysis disclosed that the hydrogen bonds occurred between the
      OR (R=CH3 and C2H5) oxygen and N-H nitrogen atoms of the selected compounds and
      the receptor site (GLN and GLU) of ChEs. PCA-QSAR indicated that the correlation
      coefficients of the electronic variables were dominant compared to the structural
      descriptors. MLR-QSAR models clarified that the net charges of nitrogen and
      phosphorus atoms contribute important electronic function in the inhibition of
      ChEs. The validity of the QSAR model was confirmed by a LOO cross-validation
      method with q2=0.965 between the training and testing sets.

PMID- 24893120
TI  - Affinity purification of recombinant human cytochrome P450s 3A4 and 1A2 using
      mixed micelle systems.
AB  - Recombinant cytochrome P450 (CYP or P450) enzymes are useful for drug metabolism
      research and thereby many expression and purification systems have been
      developed. Here, we provide a method for the purification of human P450s 3A4 and
      1A2 expressed in Escherichia coli using mixed micelles containing anionic
      phospholipids. This method does not require any protein-tagging system for
      protein isolation and has a further advantage that the purification is
      concomitantly conducted with reconstitution of the enzymes into a phospholipid
      environment, which is crucial for the catalytic activity assay of P450 enzyme.
      This method may also be applied to high-throughput catalytic assays of the
      enzymes because the purification procedures can be undertaken in a 96-well plate.

PMID- 24893122
TI  - Incidence and predictors of right ventricular pacing-induced cardiomyopathy.
AB  - BACKGROUND: Frequent right ventricular (RV) pacing can lead to a decline in left
      ventricular ejection fraction (LVEF). OBJECTIVE: This study aimed to identify
      incidence and predictors of RV pacing-induced cardiomyopathy (PICM). METHODS: We
      retrospectively studied 1750 consecutive patients undergoing pacemaker
      implantation between 2003 and 2012. Patients were included if baseline LVEF was
      normal, single-chamber ventricular or dual-chamber pacemaker (but not implantable
      cardioverter-defibrillator or biventricular pacemaker) was implanted, frequent
      (>=20%) RV pacing was present, and repeat echocardiogram was available >=1 year
      after implantation. PICM was defined as >=10% decrease in LVEF, resulting in LVEF
      <50%. Patients with alternative causes of cardiomyopathy were excluded.
      Predictors of the development of PICM were identified using multivariate Cox
      proportional hazards modeling. RESULTS: Of 257 patients meeting study criteria,
      50 (19.5%) developed PICM, with a decrease in mean LVEF from 62.1% to 36.2% over
      a mean follow-up period of 3.3 years. Those who developed PICM were more likely
      to be men, with lower baseline LVEF and wider native QRS duration (bundle branch
      blocks excluded; P = .005, P = .03, and P = .001, respectively). In multivariate
      analysis, male gender (hazard ratio 2.15; 95% confidence interval 1.17-3.94; P =
      .01) and wider native QRS duration (hazard ratio 1.03 per 1 ms increase; 95%
      confidence interval 1.01-1.05; P < .001) were independently associated with the
      development of PICM. Native QRS duration >115 ms was 90% specific for the
      development of PICM. CONCLUSION: PICM may be more common than previously
      reported, and risk for its occurrence begins below the commonly accepted
      threshold of 40% pacing burden. Men with wider native QRS duration (particularly
      >115 ms) are at increased risk. These patients warrant closer follow-up with a
      lower threshold for biventricular pacing.

PMID- 24893123
TI  - Sudden death in athletes: preventable or inevitable?

PMID- 24893125
TI  - Depletion of hepatic stellate cells: have Kupffer cells lost their bad neighbor?

PMID- 24893126
TI  - At the end of the day, should we consider chronic histological lesions?

PMID- 24893127
TI  - Knowledge and beliefs about breastfeeding are not determinants for successful
      breastfeeding.
AB  - A cross-sectional prospective study was performed to assess knowledge and
      attitude toward breastfeeding among mothers in a tertiary hospital in Malaysia
      and its influence on their breastfeeding practices. Two hundred thirteen women
      who had delivered healthy babies at term were enrolled. A structured
      questionnaire containing demographic data and the Iowa Infant Feeding Attitude
      Score were used, followed by a telephone interview after 8 weeks to determine the
      feeding outcome. Women of Malay ethnicity with higher education level who had
      received breastfeeding counseling had a significantly more favorable attitude
      toward breastfeeding. Ethnicity was found to be a significant determinant in the
      success of breastfeeding, whereas returning to work was a major reason for
      discontinuing breastfeeding. In ensuring a successful breastfeeding practice,
      apart from knowledge and attitude, issues surrounding culture and traditions as
      well as improving deliverance of readily available support should be addressed.

PMID- 24893128
TI  - Bone and lymph node metastases from neuroblastoma detected by (18)F-DOPA-PET/CT
      and confirmed by posttherapy (131)I-MIBG but negative on diagnostic (123)I-MIBG
      scan.

PMID- 24893124
TI  - Development of synthetic lethality anticancer therapeutics.
AB  - The concept of synthetic lethality (the creation of a lethal phenotype from the
      combined effects of mutations in two or more genes) has recently been exploited
      in various efforts to develop new genotype-selective anticancer therapeutics.
      These efforts include screening for novel anticancer agents, identifying novel
      therapeutic targets, characterizing mechanisms of resistance to targeted therapy,
      and improving efficacies through the rational design of combination therapy. This
      review discusses recent developments in synthetic lethality anticancer
      therapeutics, including poly ADP-ribose polymerase inhibitors for BRCA1- and
      BRCA2-mutant cancers, checkpoint inhibitors for p53 mutant cancers, and small
      molecule agents targeting RAS gene mutant cancers. Because cancers are caused by
      mutations in multiple genes and abnormalities in multiple signaling pathways,
      synthetic lethality for a specific tumor suppressor gene or oncogene is likely
      cell context-dependent. Delineation of the mechanisms underlying synthetic
      lethality and identification of treatment response biomarkers will be critical
      for the success of synthetic lethality anticancer therapy. 

PMID- 24893129
TI  - Diastolic function with 16-phase gated myocardial perfusion SPECT.
AB  - Diastolic dysfunction is commonly associated with heart failure with preserved
      systolic function. Diastolic abnormality includes progressively impaired left
      ventricle (LV) relaxation, followed by pseudonormal mitral inflow pattern with
      Valsalva enhancement, and finally restrictive LV filling. Diastolic dysfunction
      may lead to left atrial dilatation with consequent atrial fibrillation. Gated
      myocardial perfusion SPECT evaluates systolic function with LV volumes and
      ejection fraction, but its ability to identify diastolic dysfunction is not
      typically considered. We correlate 16-phase gated SPECT time-volume curves with
      echo Doppler early/late diastolic flow ratios for diastolic dysfunction. 

PMID- 24893132
TI  - Numerical analysis of the influence of nucleus pulposus removal on the
      biomechanical behavior of a lumbar motion segment.
AB  - Nucleus replacement was deemed to have therapeutic potential for patients with
      intervertebral disc herniation. However, whether a patient would benefit from
      nucleus replacement is technically unclear. This study aimed to investigate the
      influence of nucleus pulposus (NP) removal on the biomechanical behavior of a
      lumbar motion segment and to further explore a computational method of
      biomechanical characteristics of NP removal, which can evaluate the mechanical
      stability of pulposus replacement. We, respectively, reconstructed three types of
      models for a mildly herniated disc and three types of models for a severely
      herniated disc based on a L4-L5 segment finite element model with computed
      tomography image data from a healthy adult. First, the NP was removed from the
      herniated disc models, and the biomechanical behavior of NP removal was
      simulated. Second, the NP cavities were filled with an experimental material
      (Poisson's ratio = 0.3; elastic modulus = 3 MPa), and the biomechanical behavior
      of pulposus replacement was simulated. The simulations were carried out under the
      five loadings of axial compression, flexion, lateral bending, extension, and
      axial rotation. The changes of the four biomechanical characteristics, i.e. the
      rotation degree, the maximum stress in the annulus fibrosus (AF), joint facet
      contact forces, and the maximum disc deformation, were computed for all models.
      Experimental results showed that the rotation range, the maximum AF stress, and
      joint facet contact forces increased, and the maximum disc deformation decreased
      after NP removal, while they changed in the opposite way after the nucleus
      cavities were filled with the experimental material. 

PMID- 24893130
TI  - S-glutathionylation enhances human cystathionine beta-synthase activity under
      oxidative stress conditions.
AB  - AIMS: Cystathionine beta-synthase (CBS) catalyzes the first and rate-limiting
      step in the two-step trans-sulfuration pathway that converts homocysteine to
      cysteine. It is also one of three major enzymes responsible for the biogenesis of
      H2S, a signaling molecule. We have previously demonstrated that CBS is activated
      in cells challenged by oxidative stress, but the underlying molecular mechanism
      of this regulation has remained unclear. RESULTS: Here, we demonstrate that S
      glutathionylation of CBS enhances its activity ~2-fold in vitro. Loss of this
      post-translational modification in the presence of dithiothreitol results in
      reversal to basal activity. Cys346 was identified as the site for S
      glutathionylation by a combination of mass spectrometric, mutagenesis, and
      activity analyses. To test the physiological relevance of S-glutathionylation
      dependent regulation of CBS, HEK293 cells were oxidatively challenged with
      peroxide, which is known to enhance the trans-sulfuration flux. Under these
      conditions, CBS glutathionylation levels increased and were correlated with a ~3
      fold increase in CBS activity. INNOVATION: Collectively, our results reveal a
      novel post-translational modification of CBS, that is, glutathionylation, which
      functions as an allosteric activator under oxidative stress conditions permitting
      enhanced synthesis of both cysteine and H2S. CONCLUSIONS: Our study elucidates a
      molecular mechanism for increased cysteine and therefore glutathione, synthesis
      via glutathionylation of CBS. They also demonstrate the potential for increased
      H2S production under oxidative stress conditions, particularly in tissues where
      CBS is a major source of H2S.

PMID- 24893133
TI  - H7N9: A killer in the making or a false alarm?
AB  - Influenza virus remains one of the most important disease-causing viruses owing
      to its high adaptability and even higher contagious nature. Thus, it poses a
      constant threat of pandemic, engulfing a large population within the smallest
      possible time interval. A similar threat was anticipated with the identification
      of the novel H7N9 virus in China on 30 March 2013. Detection of transmission of
      the virus between humans has caused a stir with the identification of family
      clusters along with sporadic infections all across China. In this review we
      analyze the potential of the novel H7N9 virus as a probable cause of a pandemic
      and the possible consequences thereof. 

PMID- 24893131
TI  - ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and
      are disrupted by ALS/FTD-associated TDP-43.
AB  - Mitochondria and the endoplasmic reticulum (ER) form tight structural
      associations and these facilitate a number of cellular functions. However, the
      mechanisms by which regions of the ER become tethered to mitochondria are not
      properly known. Understanding these mechanisms is not just important for
      comprehending fundamental physiological processes but also for understanding
      pathogenic processes in some disease states. In particular, disruption to ER
      mitochondria associations is linked to some neurodegenerative diseases. Here we
      show that the ER-resident protein VAPB interacts with the mitochondrial protein
      tyrosine phosphatase-interacting protein-51 (PTPIP51) to regulate ER-mitochondria
      associations. Moreover, we demonstrate that TDP-43, a protein pathologically
      linked to amyotrophic lateral sclerosis and fronto-temporal dementia perturbs ER
      mitochondria interactions and that this is associated with disruption to the VAPB
      PTPIP51 interaction and cellular Ca(2+) homeostasis. Finally, we show that
      overexpression of TDP-43 leads to activation of glycogen synthase kinase-3beta
      (GSK-3beta) and that GSK-3beta regulates the VAPB-PTPIP51 interaction. Our
      results describe a new pathogenic mechanism for TDP-43. 

PMID- 24893134
TI  - Isotope analysis of sulfur, bromine, and chlorine in individual anionic species
      by ion chromatography/multicollector-ICPMS.
AB  - We developed an analytical method for precise and accurate analysis of
      delta(34)S, delta(81)Br, and delta(37)Cl in individual anionic species by coupled
      ion chromatography (IC) and multicollector inductively coupled plasma mass
      spectrometry (MC-ICPMS). The method is based on the online separation and
      purification of ions by IC prior to their isotope analysis by MC-ICPMS. The
      developed technique significantly simplifies delta(34)S, delta(81)Br, and
      delta(37)Cl analysis in environmental samples. In cases when several anionic
      species of the same element are present in the sample, they might be analyzed in
      a single analytical run. Major isobaric interferences for the analyzed elements
      were reduced by using "dry" plasma conditions and applying sufficient mass
      resolution power. The sample-standard bracketing technique was used for
      instrumental drift correction. In the case of delta(34)S analysis, precisions up
      to 0.150/00 (1sd) have been achieved for analytes containing down to 5 nmol of S;
      for delta(81)Br, the attained precision was 0.10/00 (1sd) for analytes containing
      down to 0.6 nmol of Br. Precisions of 0.20/00 have been obtained for delta(37)Cl
      with analytes containing 0.7 MUmol of Cl. Robustness of the developed analytical
      method, as well as high precisions and accuracies, has been demonstrated for the
      laboratory standard solutions and for environmental samples. 

PMID- 24893135
TI  - Pheochromocytoma and paraganglioma: an endocrine society clinical practice
      guideline.
AB  - OBJECTIVE: The aim was to formulate clinical practice guidelines for
      pheochromocytoma and paraganglioma (PPGL). PARTICIPANTS: The Task Force included
      a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS),
      seven experts in the field, and a methodologist. The authors received no
      corporate funding or remuneration. EVIDENCE: This evidence-based guideline was
      developed using the Grading of Recommendations, Assessment, Development, and
      Evaluation (GRADE) system to describe both the strength of recommendations and
      the quality of evidence. The Task Force reviewed primary evidence and
      commissioned two additional systematic reviews. CONSENSUS PROCESS: One group
      meeting, several conference calls, and e-mail communications enabled consensus.
      Committees and members of the Endocrine Society, European Society of
      Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of
      the guidelines. CONCLUSIONS: The Task Force recommends that initial biochemical
      testing for PPGLs should include measurements of plasma free or urinary
      fractionated metanephrines. Consideration should be given to preanalytical
      factors leading to false-positive or false-negative results. All positive results
      require follow-up. Computed tomography is suggested for initial imaging, but
      magnetic resonance is a better option in patients with metastatic disease or when
      radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy
      is a useful imaging modality for metastatic PPGLs. We recommend consideration of
      genetic testing in all patients, with testing by accredited laboratories.
      Patients with paraganglioma should be tested for SDHx mutations, and those with
      metastatic disease for SDHB mutations. All patients with functional PPGLs should
      undergo preoperative blockade to prevent perioperative complications. Preparation
      should include a high-sodium diet and fluid intake to prevent postoperative
      hypotension. We recommend minimally invasive adrenalectomy for most
      pheochromocytomas with open resection for most paragangliomas. Partial
      adrenalectomy is an option for selected patients. Lifelong follow-up is suggested
      to detect recurrent or metastatic disease. We suggest personalized management
      with evaluation and treatment by multidisciplinary teams with appropriate
      expertise to ensure favorable outcomes.

PMID- 24893137
TI  - Second-line treatment for advanced thyroid cancer: an indication in need of
      randomized clinical trials.

PMID- 24893136
TI  - Regulation of endocrine-disrupting chemicals insufficient to safeguard public
      health.

PMID- 24893143
TI  - All about your hormones: your body's chemical messengers.

PMID- 24893144
TI  - A harmonised approach for identifying core foods for total diet studies.
AB  - Total diet studies (TDS) are used to gather information on chemical substances in
      food, thereby facilitating risk assessments and health monitoring. Candidate
      foods for inclusion in a TDS should represent a large part of a typical diet to
      estimate accurately the exposure of a population and/or specific population
      groups. There are currently no harmonised guidelines for the selection of foods
      in a TDS, and so the aim of this study was to explore the possibility of
      generating a harmonised approach to be used across Europe. Summary statistics
      data from the European Food Safety Authority's (EFSA) Comprehensive Food
      Consumption Database were used in this research, which provided data from
      national food consumption surveys in Europe. The chosen methodology for the
      selection of foods was based on the weight of food consumed and consumer rate.
      Using the available data, 59 TDS food lists were created, representing over 51
      000 people across 17 countries and seven population groups. All TDS food lists
      represented > 85% of the populations' diets (85.9-96.3%), while the number of
      foods in the TDS food lists ranged from 15 to 102. Comparison of the TDS food
      lists indicated that the most commonly consumed foods included wheat bread and
      rolls, pastries and cakes, tomatoes, apples, bananas, and chicken, while cow's
      milk, tap water and orange juice were the most commonly consumed beverages across
      Europe. This work was complete to support EFSA and other institutions in the
      development of harmonised TDS into the future. 

PMID- 24893145
TI  - Different involvement of extracellular calcium in two modes of cell death induced
      by nanosecond pulsed electric fields.
AB  - Exposure of cultured cells to nanosecond pulsed electric fields (nsPEFs) induces
      various cellular responses, including the influx of extracellular Ca2+ and cell
      death. Recently, nsPEFs have been regarded as a novel means of cancer therapy,
      but their molecular mechanism of action remains to be fully elucidated. Here, we
      demonstrate the involvement of extracellular Ca2+ in nsPEF-induced cell death.
      Extracellular Ca2+ was essential for necrosis and consequent poly(ADP-ribose)
      (PAR) formation in HeLa S3 cells. Treatment with a Ca2+ ionophore enhanced
      necrosis as well as PAR formation in nsPEF-exposed HeLa S3 cells. In the absence
      of extracellular Ca2+, HeLa S3 cells were less susceptible to nsPEFs and
      exhibited apoptotic proteolysis of caspase 3 and PARP-1. HeLa S3 cells retained
      the ability to undergo apoptosis even after nsPEF exposure but instead underwent
      necrosis, suggesting that necrosis is the preferential mode of cell death. In
      K562 and HEK293 cells, exposure to nsPEFs resulted in the formation of necrosis
      associated PAR, whereas Jurkat cells exclusively underwent apoptosis
      independently of extracellular Ca2+. These observations demonstrate that the mode
      of cell death induced by nsPEFs is cell-type dependent and that extracellular
      Ca2+ is a critical factor for nsPEF-induced necrosis.

PMID- 24893146
TI  - Regulation of energy metabolism by the skeleton: osteocalcin and beyond.
AB  - The skeleton has recently emerged as an endocrine organ implicated in the
      regulation of glucose and energy metabolism. This function of bone is mediated,
      at least in part, by osteocalcin, an osteoblast-derived protein acting as a
      hormone stimulating insulin sensitivity, insulin secretion and energy
      expenditure. Osteocalcin secretion and bioactivity is in turn regulated by
      several hormonal cues including insulin, leptin, the sympathetic nervous system
      and glucocorticoids. Recent findings support the notion that osteocalcin
      functions and regulations are conserved between mice and humans. Moreover,
      studies in mice suggest that osteocalcin could represent a viable therapeutic
      approach for the treatment of obesity and insulin resistance. In this review, we
      summarize the current knowledge on osteocalcin functions, its various modes of
      action and the mechanisms implicated in the control of this hormone. 

PMID- 24893147
TI  - Effects of the melanin precursor 5,6-dihydroxy-indole-2-carboxylic acid (DHICA)
      on DNA damage and repair in the presence of reactive oxygen species.
AB  - Eumelanin is a heterogeneous polymer composed of 5,6-dihydroxyindole-2-carboxylic
      acid (DHICA) and 5,6-dihydroxyindole (DHI). Studies have shown that DHICA
      promotes single strand breaks in plasmid DNA exposed to ultraviolet B radiation
      (UVB, 313 nm) and in DNA from human keratinocytes exposed to ultraviolet A
      radiation (UVA, 340-400 nm). Singlet molecular oxygen ((1)O2) is the main
      reactive species formed by UVA radiation on the skin. In this context, we now
      report that DHICA can cause single strand breaks in plasmid DNA even in the
      absence of light radiation. Interestingly, when DHICA was pre-oxidized by (1)O2,
      it lost this harmful capacity. It was also found that DHICA could interact with
      DNA, disturbing Fpg activity and decreasing its recognition of lesions by ~50%.
      Additionally, the free nucleoside deoxyguanosine (dGuo) was used to evaluate
      whether DHICA would interfere with the formation of 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodGuo) and spiroiminodihydantoin (dSp) by (1)O2 or with the
      formation of 8-oxodGuo by hydroxyl radical (OH). We observed that when dGuo was
      oxidized by (1)O2 in the presence of DHICA, 8-oxodGuo formation was increased.
      However, when dGuo was oxidized by OH in the presence of DHICA, 8-oxodGuo levels
      were lower than in the absence of the precursor. Overall, our data reveal an
      important role for this eumelanin precursor in both the promotion and the
      protection of DNA damage and imply that it can impair DNA repair.

PMID- 24893148
TI  - Specific localization of quercetin-3-O-glucuronide in human brain.
AB  - In recent years, many papers have suggested that dietary flavonoids may exert
      beneficial effects in the brain tissue for the protection of neurons against
      oxidative stress and inflammation. However, the bioavailability of flavonoids
      across the blood-brain barrier and the localization in the brain remain
      controversial. Thus, we examined the localization of quercetin-3-O-glucuronide
      (Q3GA), a major phase-II metabolite of quercetin, in the human brain tissues with
      or without cerebral infarction by immunohistochemical staining using anti-Q3GA
      antibody. A significant immunoreactivity was observed in the epithelial cells of
      the choroid plexus, which constitute the structural basis of the blood
      cerebrospinal fluid (CSF) barrier, and in the foamy macrophages of recent
      infarcts. The cellular accumulation of Q3GA was also reproduced in vitro in
      macrophage-like RAW264, microglial MG6, and brain capillary endothelial RBEC1. It
      is of interest that a common feature of these cell lines is the deconjugation of
      Q3GA, resulting in the cellular accumulation of non-conjugated quercetin and the
      methylated forms. We then examined the anti-inflammatory activity of Q3GA and the
      deconjugated forms in the lipopolysaccharide-stimulated macrophage cells and
      revealed that the deconjugated forms (quercetin and a methylated form
      isorhamnetin), but not Q3GA itself, exhibited inhibitory effects on the
      inflammatory responses through attenuation of the c-Jun N-terminal kinase
      pathway. These results suggested that a quercetin glucuronide can pass through
      the blood-brain barrier, perhaps the CSF barrier, accumulate in specific types of
      cells, such as macrophages, and act as anti-inflammatory agents in the brain
      through deconjugation into the bioactive non-conjugated forms. 

PMID- 24893150
TI  - The forgotten: dementia and the aging LGBT community.
AB  - Although research documenting the experience of lesbian, gay, bisexual,
      transgendered (LGBT) aging in general is gaining traction, and literature on
      dementia continues to proliferate, few articles attend to how dementia affects
      members of the aging LGBT community. This article reviews the current state of
      knowledge on the experience of dementia for LGBT older adults, and suggests areas
      for further research. In addition, it aims to promote social work's engagement
      with related disciplines and global dementia care. The article's ultimate goal is
      to encourage development of care practices tailored to the experiences,
      expectations and needs of older LGBT individuals affected by dementia.

PMID- 24893149
TI  - ATP allosterically activates the human 5-lipoxygenase molecular mechanism of
      arachidonic acid and 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic
      acid.
AB  - 5-Lipoxygenase (5-LOX) reacts with arachidonic acid (AA) to first generate 5(S)
      hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid [5(S)-HpETE] and then an
      epoxide from 5(S)-HpETE to form leukotriene A4, from a single polyunsaturated
      fatty acid. This work investigates the kinetic mechanism of these two processes
      and the role of ATP in their activation. Specifically, it was determined that
      epoxidation of 5(S)-HpETE (dehydration of the hydroperoxide) has a rate of
      substrate capture (Vmax/Km) significantly lower than that of AA hydroperoxidation
      (oxidation of AA to form the hydroperoxide); however, hyperbolic kinetic
      parameters for ATP activation indicate a similar activation for AA and 5(S)
      HpETE. Solvent isotope effect results for both hydroperoxidation and epoxidation
      indicate that a specific step in its molecular mechanism is changed, possibly
      because of a lowering of the dependence of the rate-limiting step on hydrogen
      atom abstraction and an increase in the dependency on hydrogen bond
      rearrangement. Therefore, changes in ATP concentration in the cell could affect
      the production of 5-LOX products, such as leukotrienes and lipoxins, and thus
      have wide implications for the regulation of cellular inflammation. 

PMID- 24893151
TI  - Association of varicella zoster virus with giant cell arteritis.

PMID- 24893152
TI  - Surface modification by allylamine plasma polymerization promotes osteogenic
      differentiation of human adipose-derived stem cells.
AB  - Tuning the material properties in order to control the cellular behavior is an
      important issue in tissue engineering. It is now well-established that the
      surface chemistry can affect cell adhesion, proliferation, and differentiation.
      In this study, plasma polymerization, which is an appealing method for surface
      modification, was employed to generate surfaces with different chemical
      compositions. Allylamine (AAm), acrylic acid (AAc), 1,7-octadiene (OD), and
      ethanol (ET) were used as precursors for plasma polymerization in order to
      generate thin films rich in amine (-NH2), carboxyl (-COOH), methyl (-CH3), and
      hydroxyl (-OH) functional groups, respectively. The surface chemistry was
      characterized by X-ray photoelectron spectroscopy (XPS), the wettability was
      determined by measuring the water contact angles (WCA) and the surface topography
      was imaged by atomic force microscopy (AFM). The effects of surface chemical
      compositions on the behavior of human adipose-derive stem cells (hASCs) were
      evaluated in vitro: Cell Count Kit-8 (CCK-8) analysis for cell proliferation, F
      actin staining for cell morphology, alkaline phosphatase (ALP) activity analysis,
      and Alizarin Red S staining for osteogenic differentiation. The results show that
      AAm-based plasma-polymerized coatings can promote the attachment, spreading, and,
      in turn, proliferation of hASCs, as well as promote the osteogenic
      differentiation of hASCs, suggesting that plasma polymerization is an appealing
      method for the surface modification of scaffolds used in bone tissue engineering.

PMID- 24893153
TI  - Design and development of heterologous competitive immunoassays for the
      determination of boscalid residues.
AB  - Boscalid is a modern agrochemical belonging to the so-called chemical class of
      succinate dehydrogenase inhibitor fungicides. With the aim of developing rapid
      analytical screening methods for this relevant compound, we herein report the
      synthesis of new boscalid mimics and the study of their suitability for the
      production of polyclonal antibodies. Aliphatic spacer arms equivalent in length
      and composition were tethered at two different aromatic rings of the target
      molecular structure. These haptens, besides being used for immunization, were
      employed in the development of heterologous competitive enzyme-linked
      immunosorbent assays (cELISAs) in order to improve assay detectability. Direct
      and indirect immunoassays were tailored and applied to the determination of
      samples with incurred boscalid residues. The assays were characterized in terms
      of sensitivity, specificity, trueness, and precision. Limit of quantification was
      established at 5 MUg kg(-1), coefficients of variation were lower than 20%, and
      recoveries from spiked samples ranged from 90 to 137%. Finally, ELISA performance
      was evaluated by Deming regression analysis with tomato and cucumber samples,
      selecting ultra-performance liquid chromatography-mass spectrometry as the
      reference method. The results showed that the proposed cELISAs are useful for the
      routine determination of boscalid fungicides in foods with high-sample throughput
      and affordable cost. 

PMID- 24893155
TI  - Integrating emerging treatment options in mantle cell lymphoma.
AB  - Mantle cell lymphoma is an uncommon lymphoma subtype that is currently considered
      incurable and lacks a single standard of care. Choice of treatment is complicated
      by the disease's clinical heterogeneity. The course of the disease may be
      indolent, moderately aggressive, or aggressive. A translocation between
      chromosomes 11 and 14 is observed in the majority of mantle cell lymphoma
      patients, and the diseased cells may develop a variety of other genetic
      aberrations. Although the disease tends to respond well to treatment, patients
      almost invariably relapse, with many becoming chemotherapy refractory over time.
      The development of new treatment strategies has improved the prognosis for these
      patients. Novel approaches include intensive chemotherapy, often in combination
      with stem cell transplantation; maintenance therapy with extended duration; and
      new targeted treatments such as ibrutinib, bendamustine, bortezomib,
      lenalidomide, and idelalisib. Many of these new agents have shown promising
      activity, both as single agents and in combination regimens.

PMID- 24893154
TI  - Different modulation of common motor information in rat primary and secondary
      motor cortices.
AB  - Rodents have primary and secondary motor cortices that are involved in the
      execution of voluntary movements via their direct and parallel projections to the
      spinal cord. However, it is unclear whether the rodent secondary motor cortex has
      any motor function distinct from the primary motor cortex to properly control
      voluntary movements. In the present study, we quantitatively examined neuronal
      activity in the caudal forelimb area (CFA) of the primary motor cortex and
      rostral forelimb area (RFA) of the secondary motor cortex in head-fixed rats
      performing forelimb movements (pushing, holding, and pulling a lever). We found
      virtually no major differences between CFA and RFA neurons, regardless of neuron
      subtypes, not only in their basal spiking properties but also in the time-course,
      amplitude, and direction preference of their functional activation for simple
      forelimb movements. However, the RFA neurons, as compared with the CFA neurons,
      showed obviously a greater susceptibility of their functional activation to an
      alteration in a behavioral situation, a 'rewarding' response that leads to reward
      or a 'consummatory' response that follows reward water, which might be
      accompanied by some internal adaptations without affecting the motor outputs. Our
      results suggest that, although the CFA and RFA neurons commonly process
      fundamental motor information to properly control forelimb movements, the RFA
      neurons may be functionally differentiated to integrate motor information with
      internal state information for an adaptation to goal-directed behaviors. 

PMID- 24893160
TI  - From transmission to transition: lessons learnt from the Thai paediatric
      antiretroviral programme.
AB  - BACKGROUND: The Thai HIV programme is a leader in the public health approach to
      HIV treatment. Starting at transmission of HIV and ending with transition to
      adult services this paper assesses the paediatric HIV treatment continuum from
      three perspectives: service-user, provider and policy maker, to understand what
      works well and why. METHODS: A qualitative research design was used to assess and
      triangulate the stakeholder perspectives. Semi-structured interviews were
      conducted with ART service-users (n = 35), policy actors (n = 20); telephone
      interviews with prior caregivers of orphans (n = 10); and three focus group
      discussions with service-providers (hospital staff and volunteers) from a
      district, provincial and a university hospital. FINDINGS: Children accessing HIV
      care were often orphaned, cared for by elderly relatives and experiencing
      multiple vulnerabilities. Services were divided into three stages, 1. Diagnosis
      and linkage: Despite strong policies there were supply and demand-side gaps in
      the prevention of mother-to-child transmission 'cascade' preventing early
      diagnosis and/or treatment. 2. Maintenance on ART - Children did well on
      treatment; caregivers took adherence seriously and valued the quality of
      services. Drug resistance, adherence and psychosocial issues were important
      concerns from all perspectives. 3. Adolescents and transition: Adolescent service
      users faced greater complexity in their physical and emotional lives for which
      providers lacked skills; transition from the security of paediatric clinic was a
      daunting prospect. Dedicated healthcare providers felt they struggled to deliver
      services that met service-users' diverse needs at all stages. Child- and
      adolescent-specific elements of HIV policy were considered low priority.
      CONCLUSIONS: Using the notion of the continuum of care a number of strengths and
      weaknesses were identified. Features of paediatric services need to evolve
      alongside the changing needs of service users. Peer-support volunteers have
      potential to add continuity and support at all stages. It is critical that
      adolescents receive targeted support, particularly during transition to adult
      services.

PMID- 24893161
TI  - Potassium and the excitability properties of normal human motor axons in vivo.
AB  - Hyperkalemia is an important cause of membrane depolarization in renal failure. A
      recent theoretical model of axonal excitability explains the effects of potassium
      on threshold electrotonus, but predicts changes in superexcitability in the
      opposite direction to those observed. To resolve this contradiction we assessed
      the relationship between serum potassium and motor axon excitability properties
      in 38 volunteers with normal potassium levels. Most threshold electrotonus
      measures were strongly correlated with potassium, and superexcitability decreased
      at higher potassium levels (P = 0.016), contrary to the existing model. Improved
      modelling of potassium effects was achieved by making the potassium currents obey
      the constant-field theory, and by making the potassium permeabilities
      proportional to external potassium, as has been observed in vitro. This new model
      also accounted well for the changes in superexcitability and other excitability
      measures previously reported in renal failure. These results demonstrate the
      importance of taking potassium levels into account when assessing axonal membrane
      dysfunction by excitability testing, and provide evidence that potassium currents
      are activated by external potassium in vivo.

PMID- 24893163
TI  - Satellite tracking of sympatric marine megafauna can inform the biological basis
      for species co-management.
AB  - CONTEXT: Systematic conservation planning is increasingly used to identify
      priority areas for protection in marine systems. However, ecosystem-based
      approaches typically use density estimates as surrogates for animal presence and
      spatial modeling to identify areas for protection and may not take into account
      daily or seasonal movements of animals. Additionally, sympatric and inter-related
      species are often managed separately, which may not be cost-effective. This study
      aims to demonstrate an evidence-based method to inform the biological basis for
      co-management of two sympatric species, dugongs and green sea turtles. This
      approach can then be used in conservation planning to delineate areas to maximize
      species protection. METHODOLOGY/RESULTS: Fast-acquisition satellite telemetry was
      used to track eleven dugongs and ten green turtles at two geographically distinct
      foraging locations in Queensland, Australia to evaluate the inter- and intra
      species spatial relationships and assess the efficacy of existing protection
      zones. Home-range analysis and bathymetric modeling were used to determine
      spatial use and compared with existing protection areas using GIS. Dugong and
      green turtle home-ranges significantly overlapped in both locations. However,
      both species used different core areas and differences existed between regions in
      depth zone use and home-range size, especially for dugongs. Both species used
      existing protection areas in Shoalwater Bay, but only a single tracked dugong
      used the existing protection area in Torres Strait. CONCLUSIONS/SIGNIFICANCE:
      Fast-acquisition satellite telemetry can provide evidence-based information on
      individual animal movements to delineate relationships between dugongs and green
      turtles in regions where they co-occur. This information can be used to increase
      the efficacy of conservation planning and complement more broadly based survey
      information. These species also use similar habitats, making complimentary co
      management possible, but important differences exist between locations making it
      essential to customize management. This methodology could be applied on a broader
      scale to include other sympatric and inter-related species.

PMID- 24893162
TI  - Sham surgery and inter-individual heterogeneity are major determinants of
      monocyte subset kinetics in a mouse model of myocardial infarction.
AB  - AIMS: Mouse models of myocardial infarction (MI) are commonly used to explore the
      pathophysiological role of the monocytic response in myocardial injury and to
      develop translational strategies. However, no study thus far has examined the
      potential impact of inter-individual variability and sham surgical procedures on
      monocyte subset kinetics after experimental MI in mice. Our goal was to
      investigate determinants of systemic myeloid cell subset shifts in C57BL/6 mice
      following MI by developing a protocol for sequential extensive flow cytometry
      (FCM). METHODS AND RESULTS: Following cross-sectional multiplex FCM analysis we
      provide for the first time a detailed description of absolute quantities,
      relative subset composition, and biological variability of circulating classical,
      intermediate, and non-classical monocyte subsets in C57BL/6 mice. By using intra
      individual longitudinal measurements after MI induction, a time course of
      classical and non-classical monocytosis was recorded. This approach disclosed a
      significant reduction of monocyte subset dispersion across all investigated time
      points following MI. We found that in the current invasive model of chronic MI
      the global pattern of systemic monocyte kinetics is mainly determined by a
      nonspecific inflammatory response to sham surgery and not by the extent of
      myocardial injury. CONCLUSIONS: Application of sequential multiplexed FCM may
      help to reduce the impact of biological variability in C57BL/6 mice. Furthermore,
      the confounding influence of sham surgical procedures should always be considered
      when measuring monocyte subset kinetics in a murine model of MI.

PMID- 24893164
TI  - CD271+ osteosarcoma cells display stem-like properties.
AB  - Cancer stem cell (CSC) theory has been proposed and verified in many cancers. The
      existence of osteosarcoma CSCs has been confirmed for many years and multiple
      surface markers have been employed to identify them. In this study, we identified
      CD271(+) subpopulation of osteosarcoma displaying stem-like properties. CD271,
      known as the neural crest nerve growth factor receptor, is the marker of bone
      marrow mesenchymal stem cells (MSCs) and human melanoma-initiating cells. We
      discovered that CD271 was expressed differentially in diverse types of human
      osteosarcoma and stabilized cell lines. CD271(+) osteosarcoma cells displayed
      most of the properties of CSC, such as self-renewal, differentiation, drug
      resistance and tumorigenicity in vivo. Nanog, Oct3/4, STAT3, DNA-PKcs, Bcl-2 and
      ABCG2 were more expressed in CD271(+) cells compared with CD271- cells. Our study
      supported the osteosarcoma CSC hypothesis and, to a certain extent, revealed one
      of the possible mechanisms involved in maintaining CSCs properties.

PMID- 24893165
TI  - Alisertib added to rituximab and vincristine is synthetic lethal and potentially
      curative in mice with aggressive DLBCL co-overexpressing MYC and BCL2.
AB  - Pearson correlation coefficient for expression analysis of the Lymphoma/Leukemia
      Molecular Profiling Project (LLMPP) demonstrated Aurora A and B are highly
      correlated with MYC in DLBCL and mantle cell lymphoma (MCL), while both Auroras
      correlate with BCL2 only in DLBCL. Auroras are up-regulated by MYC dysregulation
      with associated aneuploidy and resistance to microtubule targeted agents such as
      vincristine. Myc and Bcl2 are differentially expressed in U-2932, TMD-8, OCI-Ly10
      and Granta-519, but only U-2932 cells over-express mutated p53. Alisertib
      [MLN8237 or M], a highly selective small molecule inhibitor of Aurora A kinase,
      was synergistic with vincristine [VCR] and rituximab [R] for inhibition of cell
      proliferation, abrogation of cell cycle checkpoints and enhanced apoptosis versus
      single agent or doublet therapy. A DLBCL (U-2932) mouse model showed tumor growth
      inhibition (TGI) of ~ 10-20% (p = 0.001) for M, VCR and M-VCR respectively, while
      R alone showed ~ 50% TGI (p = 0.001). M-R and VCR-R led to tumor regression [TR],
      but relapsed 10 days after discontinuing therapy. In contrast, M-VCR-R
      demonstrated TR with no relapse >40 days after stopping therapy with a Kaplan
      Meier survival of 100%. Genes that are modulated by M-VCR-R (CENP-C, Auroras)
      play a role in centromere-kinetochore function in an attempt to maintain mitosis
      in the presence of synthetic lethality. Together, our data suggest that the
      interaction between alisertib plus VCR plus rituximab is synergistic and
      synthetic lethal in Myc and Bcl-2 co-expressing DLBCL. Alisertib plus vincristine
      plus rituximab [M-VCR-R] may represent a new strategy for DLBCL therapy.

PMID- 24893166
TI  - On a dhole trail: examining ecological and anthropogenic correlates of dhole
      habitat occupancy in the Western ghats of India.
AB  - Although they play a critical role in shaping ecological communities, many
      threatened predator species are data-deficient. The Dhole Cuon alpinus is one
      such rare canid with a global population thought to be <2500 wild individuals. We
      assessed habitat occupancy patterns of dholes in the Western Ghats of Karnataka,
      India, to understand ecological and anthropogenic determinants of their
      distribution and habitat-use. We conducted spatially replicated detection/non
      detection surveys of dhole signs along forest trails at two appropriate scales:
      the entire landscape and a single wildlife reserve. Landscape-scale habitat
      occupancy was assessed across 38,728 km(2) surveying 206 grid cells of 188-km(2)
      each. Finer scale habitat-use within 935 km2 Bandipur Reserve was studied
      surveying 92 grid cells of 13-km(2) km each. We analyzed the resulting data of
      dhole signs using likelihood-based habitat occupancy models. The models
      explicitly addressed the problematic issue of imperfect detection of dhole signs
      during field surveys as well as potential spatial auto-correlation between sign
      detections made on adjacent trail segments. We show that traditional 'presence
      versus absence' analyses underestimated dhole habitat occupancy by 60% or 8682
      km2 [naive = 0.27; psiL(SE)  = 0.68 (0.08)] in the landscape. Addressing
      imperfect sign detections by estimating detection probabilities [p(t)(L) (SE) =
      0.12 (0.11)] was critical for reliable estimation. Similar underestimation
      occurred while estimating habitat-use probability at reserve-scale [naive = 0.39;
      Psis(SE) = 0.71 (0.06)]. At landscape scale, relative abundance of principal
      ungulate prey primarily influenced dhole habitat occupancy. Habitat-use within a
      reserve, however, was predominantly and negatively influenced by anthropogenic
      disturbance. Our results are the first rigorous assessment of dhole occupancy at
      multiple spatial scales with potential conservation value. The approach used in
      this study has potential utility for cost-effectively assessing spatial
      distribution and habitat-use in other species, landscapes and reserves.

PMID- 24893167
TI  - A century of the evolution of the urban area in Shenyang, China.
AB  - Analyzing spatiotemporal characteristics of the historical urbanization process
      is essential in understanding the dynamics of urbanization and scientifically
      planned urban development. Based on historical urban area maps and remote sensing
      images, this study examined the urban expansion of Shenyang from 1910 to 2010
      using area statistics, typology identification, and landscape metrics approaches.
      The population and gross domestic product were analyzed as driving factors. The
      results showed that the urban area of Shenyang increased 43.39-fold during the
      study period and that the growth rate has accelerated since the 1980s. Three
      urban growth types were distinguished: infilling, edge-expansion, and spontaneous
      growth. Edge-expansion was the primary growth type. Infilling growth became the
      main growth type in the periods 1946-70, 1988-97, and 2004-10. Spontaneous growth
      was concentrated in the period of 1997 to 2000. The results of landscape metrics
      indicate that the urban landscape of Shenyang originally was highly aggregated,
      but has become increasingly fragmented. The urban fringe area was the traditional
      hot zone of urbanization. Shenyang was mainly located north of the Hun River
      before 1980; however, the south side of the river has been the hot zone of
      urbanization since the 1980s. The increase of urban area strongly correlated with
      the growth of GDP and population. Over a long time scale, the urbanization
      process has been affected by major historical events. 

PMID- 24893168
TI  - Event detection using Twitter: a spatio-temporal approach.
AB  - BACKGROUND: Every day, around 400 million tweets are sent worldwide, which has
      become a rich source for detecting, monitoring and analysing news stories and
      special (disaster) events. Existing research within this field follows key words
      attributed to an event, monitoring temporal changes in word usage. However, this
      method requires prior knowledge of the event in order to know which words to
      follow, and does not guarantee that the words chosen will be the most appropriate
      to monitor. METHODS: This paper suggests an alternative methodology for event
      detection using space-time scan statistics (STSS). This technique looks for
      clusters within the dataset across both space and time, regardless of tweet
      content. It is expected that clusters of tweets will emerge during spatio
      temporally relevant events, as people will tweet more than expected in order to
      describe the event and spread information. The special event used as a case study
      is the 2013 London helicopter crash. RESULTS AND CONCLUSION: A spatio-temporally
      significant cluster is found relating to the London helicopter crash. Although
      the cluster only remains significant for a relatively short time, it is rich in
      information, such as important key words and photographs. The method also detects
      other special events such as football matches, as well as train and flight delays
      from Twitter data. These findings demonstrate that STSS is an effective approach
      to analysing Twitter data for event detection.

PMID- 24893169
TI  - Mass spectrometry based identification of geometric isomers during metabolic
      stability study of a new cytotoxic sulfonamide derivatives supported by
      quantitative structure-retention relationships.
AB  - A set of 15 new sulphonamide derivatives, presenting antitumor activity have been
      subjected to a metabolic stability study. The results showed that besides
      products of biotransformation, some additional peaks occurred in chromatograms.
      Tandem mass spectrometry revealed the same mass and fragmentation pathway,
      suggesting that geometric isomerization occurred. Thus, to support this
      hypothesis, quantitative structure-retention relationships were applied. Human
      liver microsomes were used as an in vitro model of metabolism. The
      biotransformation reactions were tracked by liquid chromatography assay and
      additionally, fragmentation mass spectra were recorded. In silico molecular
      modeling at a semi-empirical level was conducted as a starting point for
      molecular descriptor calculations. A quantitative structure-retention
      relationship model was built applying multiple linear regression based on
      selected three-dimensional descriptors. The studied compounds revealed high
      metabolic stability, with a tendency to form hydroxylated biotransformation
      products. However, significant chemical instability in conditions simulating
      human body fluids was noticed. According to literature and MS data geometrical
      isomerization was suggested. The developed in sillico model was able to describe
      the relationship between the geometry of isomer pairs and their chromatographic
      retention properties, thus it supported the hypothesis that the observed pairs of
      peaks are most likely geometric isomers. However, extensive structural
      investigations are needed to fully identify isomers' geometry. An effort to
      describe MS fragmentation pathways of novel chemical structures is often not
      enough to propose structures of potent metabolites and products of other chemical
      reactions that can be observed in compound solutions at early drug discovery
      studies. The results indicate that the relatively non-expensive and not time- and
      labor-consuming in sillico approach could be a good supportive tool assisting the
      identification of cis-trans isomers based on retention data. This methodology can
      be helpful during the structural identification of biotransformation and
      degradation products of new chemical entities--potential new drugs.

PMID- 24893170
TI  - miR-19, miR-345, miR-519c-5p serum levels predict adverse pathology in prostate
      cancer patients eligible for active surveillance.
AB  - Serum microRNAs hold great promise as easily accessible and measurable biomarkers
      of disease. In prostate cancer, serum miRNA signatures have been associated with
      the presence of disease as well as correlated with previously validated risk
      models. However, it is unclear whether miRNAs can provide independent prognostic
      information beyond current risk models. Here, we focus on a group of low-risk
      prostate cancer patients who were eligible for active surveillance, but chose
      surgery. A major criteria for the low risk category is a Gleason score of 6 or
      lower based on pre-surgical biopsy. However, a third of these patients are
      upgraded to Gleason 7 on post surgical pathological analysis. Both in a discovery
      and a validation cohort, we find that pre-surgical serum levels of miR-19, miR
      345 and miR-519c-5p can help identify these patients independent of their pre
      surgical age, PSA, stage, and percent biopsy involvement. A combination of the
      three miRNAs increased the area under a receiver operator characteristics curve
      from 0.77 to 0.94 (p<0.01). Also, when combined with the CAPRA risk model the
      miRNA signature significantly enhanced prediction of patients with Gleason 7
      disease. In-situ hybridizations of matching tumors showed miR-19 upregulation in
      transformed versus normal-appearing tumor epithelial, but independent of tumor
      grade suggesting an alternative source for the increase in serum miR-19a/b levels
      or the release of pre-existing intracellular miR-19a/b upon progression.
      Together, these data show that serum miRNAs can predict relatively small steps in
      tumor progression improving the capacity to predict disease risk and, therefore,
      potentially drive clinical decisions in prostate cancer patients. It will be
      important to validate these findings in a larger multi-institutional study as
      well as with independent methodologies. 

PMID- 24893172
TI  - Identification of gene expression changes in postnatal rat foreskin after in
      utero anti-androgen exposure.
AB  - In utero human phthalate exposure has been associated with male reproductive
      disorders in epidemiological studies, but discovering relationships is hindered
      by the lack of identifying markers. This study identified gene expression changes
      following in utero dibutyl phthalate (DBP) and flutamide exposures in Sprague
      Dawley rat foreskin. Dams were exposed to 100 or 500mg/kg/day dibutyl phthalate
      or 5mg/kg/day flutamide from gestational days 16-20. Microarray analysis was
      performed on foreskin tissue from gestational day 20 and postnatal day 5.
      Expression changes found following DBP exposure were not present following
      flutamide treatment, indicating that expression changes were specific to DBP
      exposure and not caused by altered androgen signaling. Genes that were expressed
      at lower levels in tissue from pups treated with the low dose of DBP were reduced
      more in pups treated with the high dose of DBP, demonstrating a dose response
      effect of this compound. Changes in expression of Marcks, Pum1, Nupr1, and Penk
      caused by in utero phthalate exposure were confirmed by qRT-PCR. Changes in
      expression of these genes were maintained after birth and consequently their
      expression could serve as markers of chemical exposure and biological response. 

PMID- 24893171
TI  - Patterns of gene expression associated with Pten deficiency in the developing
      inner ear.
AB  - In inner ear development, phosphatase and tensin homolog (PTEN) is necessary for
      neuronal maintenance, such as neuronal survival and accurate nerve innervations
      of hair cells. We previously reported that Pten conditional knockout (cKO) mice
      exhibited disorganized fasciculus with neuronal apoptosis in spiral ganglion
      neurons (SGNs). To better understand the genes and signaling networks related to
      auditory neuron maintenance, we compared the profiles of differentially expressed
      genes (DEGs) using microarray analysis of the inner ear in E14.5 Pten cKO and
      wild-type mice. We identified 46 statistically significant transcripts using
      significance analysis of microarrays, with the false-discovery rate set at 0%.
      Among the DEGs, expression levels of candidate genes and expression domains were
      validated by quantitative real-time RT-PCR and in situ hybridization,
      respectively. Ingenuity pathway analysis using DEGs identified significant
      signaling networks associated with apoptosis, cellular movement, and axon
      guidance (i.e., secreted phosphoprotein 1 (Spp1)-mediated cellular movement and
      regulator of G-protein signaling 4 (Rgs4)-mediated axon guidance). This result
      was consistent with the phenotypic defects of SGNs in Pten cKO mice (e.g.,
      neuronal apoptosis, abnormal migration, and irregular nerve fiber patterns of
      SGNs). From this study, we suggest two key regulatory signaling networks mediated
      by Spp1 and Rgs4, which may play potential roles in neuronal differentiation of
      developing auditory neurons. 

PMID- 24893173
TI  - The protective effects of nausea and vomiting of pregnancy against adverse fetal
      outcome--a systematic review.
AB  - Studies have suggested that nausea and vomiting of pregnancy (NVP) may confer
      favorable pregnancy outcome, when compared to women not experiencing NVP.
      However, this was never examined systematically. METHODS: We systematically
      reviewed all human studies examining potential effects of NVP on rates of
      miscarriage, intrauterine growth restriction, congenital malformations,
      prematurity and developmental achievements. RESULTS: Our analysis reveals a
      consistent favorable effect of NVP on rates of miscarriages, congenital
      malformations, prematurity, and developmental achievements. The effect size was
      clinically important for miscarriage, malformations and prematurity. In a few
      studies the protective effects were more prominent in women with moderate-severe
      NVP than among those with mild or no NVP. CONCLUSIONS: NVP is associated with
      favorable fetal outcome, and therefore studies of drug exposure in pregnancy
      should either match their exposed and control cases for existence and severity of
      NVP, or adjust for these confounders in their multivariate analysis.

PMID- 24893174
TI  - Deferasirox for managing transfusional iron overload in people with sickle cell
      disease.
AB  - BACKGROUND: Sickle cell disease (SCD) is a group of genetic haemoglobin
      disorders, that occurs in about 2.2 per 1000 births worldwide. Increasingly, some
      people with SCD develop secondary iron overload due to occasional red blood cell
      transfusions or are on long-term transfusion programmes for e.g. secondary stroke
      prevention. Iron chelation therapy can prevent long-term
      complications.Deferoxamine and deferiprone have been found to be efficacious.
      However, questions exist about the effectiveness and safety of the newer oral
      chelator deferasirox. OBJECTIVES: To assess the effectiveness and safety of oral
      deferasirox in people with SCD and secondary iron overload. SEARCH METHODS: We
      searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies
      Trials Register: date of most recent search:13 March 2014.We searched MEDLINE,
      Embase, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE, EBMR and
      The Cochrane Library, respectively; date of most recent searches: 02 August
      2013.We searched four trial registries: www.controlled-trials.com;
      www.clinicaltrials.gov; www.who.int./ictrp/en/; www.drks.de; date of most recent
      searches: 03 June 2013. SELECTION CRITERIA: Randomised controlled trials
      comparing deferasirox with no therapy or placebo or with another iron chelating
      treatment schedule. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed risk of bias and extracted data. We contacted the corresponding study
      authors for additional information. MAIN RESULTS: Two studies (with 203 and 212
      people) comparing the efficacy and safety of deferasirox and deferoxamine after
      12 months and 24 weeks, respectively, were included. The overall quality,
      according to GRADE, for the main outcomes was moderate to low. Only limited data
      were available on mortality and end-organ damage, although one study did assess
      mortality, relative risk 1.26 (95% confidence interval 0.05 to 30.41), the 24
      week follow up was too short to allow us to draw firm conclusions. One study
      reported a relative risk of 1.26 for the incidence of type 2 diabetes mellitus
      (95% confidence interval 0.05 to 30.41). Serum ferritin reduction was
      significantly greater with deferoxamine, mean difference of change of 440.69 ug/l
      (95% confidence interval 11.73 to 869.64). Liver iron concentration (reported in
      one study) measured by superconduction quantum interference device showed no
      significant difference for the overall group of patients adjusted for transfusion
      category, mean difference -0.20 mg Fe/g dry weight (95% confidence interval -3.15
      to 2.75).The occurrence of serious adverse events did not differ between drugs.
      Nausea, diarrhoea and rash occurred significantly more often in people treated
      with deferasirox, while adverse events of any kind were more often reported for
      patients treated with deferoxamine (one study). The mean increase of creatinine
      was also significantly higher with deferasirox, mean difference 3.24 (95%
      confidence interval 0.45 to 6.03). Long-term adverse events could not be measured
      in the included studies (follow up 52 weeks and 24 weeks). Patient satisfaction
      and the likelihood of continuing treatment, were significantly better with
      deferasirox. AUTHORS' CONCLUSIONS: Deferasirox appears to be of similar efficacy
      to deferoxamine depending on depending on the appropriate ratio of doses of
      deferoxamine and deferasirox being compared. However, only limited evidence is
      available assessing the efficacy regarding patient-important outcomes. The short
      term safety of deferasirox seems to be acceptable, however, follow up in the
      available studies was too short to assess long-term side effects. Long-term
      safety and efficacy data are available from a non-controlled extension phase not
      included in our review; however, no valid comparative conclusions can be drawn
      and future studies should assess comparatively long-term outcomes both for safety
      and efficacy.

PMID- 24893179
TI  - Considerable different frequency dependence of dynamic tensile modulus between
      self-heating (Joule heat) and external heating for polymer--nickel-coated carbon
      fiber composites.
AB  - Dynamic tensile moduli of polyethylene--nickel-coated carbon fiber (NiCF)
      composites with 10 and 4 vol % NiCF contents under electrical field were measured
      by a homemade instrument in the frequency range of 100--0.01 Hz. The drastic
      descent of the storage modulus of the composite with 10 vol % was verified in
      lower frequency range with elevating surface temperature (T(s)) by self-heating
      (Joule heat). The composite was cut when T(s) was beyond 108  degrees C. On the
      other hand, the measurement of the composite with 4 vol % beyond 88  degrees C
      was impossible, since T(s) did not elevate because of the disruption of current
      networks. Incidentally, the dynamic tensile moduli by external heating could be
      measured up to 130 and 115  degrees C for 10 and 4 vol %, respectively, but the
      two composites could be elongated beyond the above temperatures. Such different
      properties were analyzed in terms of crystal dispersions, electrical treeing, and
      thermal fluctuation-induced tunneling effect.

PMID- 24893180
TI  - Increasing the utility of population-based birth defects surveillance program
      data.

PMID- 24893181
TI  - The utility of the National Death Index as a supplemental data source in
      ascertaining 5-year mortality among Texas heterotaxy cases.
AB  - INTRODUCTION: The Texas Birth Defects Registry (TBDR) is an active surveillance
      system which covers all pregnancy outcomes and routinely links birth defects
      cases to in-state vital records. This study describes the value of using the
      National Death Index (NDI) data to supplement Texas state death certificates from
      vital records for a birth defects survival analysis. METHODS: The cohort for this
      study were live-born cases with heterotaxy, a complex birth defect, delivered to
      Texas residents between 1999 and 2006, with a 5-year follow-up period for
      survival determination. Cases were linked to their Texas birth and death
      certificates, if present. Any live-born case that did not link to a Texas death
      certificate was sent to the NDI to search for any deaths that occurred. RESULTS:
      We identified 366 heterotaxy cases that were live-born in delivery years 1999
      2006, 134 of which were linked to a Texas death certificate. The 232 remaining
      cases were sent to the NDI to search for a death certificate not found
      previously. This resulted in only 2 additional out-of-state deaths. DISCUSSION:
      Future quantification of NDI yields for birth defects survival studies would
      assist with further assessing the efficacy of utilizing the NDI for capturing
      early childhood mortality in states that routinely link to in-state death
      certificates.

PMID- 24893182
TI  - Multiple congenital anomalies: issues for birth defects surveillance.
AB  - Approximately 1 in 200 individuals and 20 percent to 30 percent of those in whom
      any major structural malformation is found will have 2 or more serious and
      potentially unrelated birth defects. In addition to the challenges that multiple
      malformations create for affected persons, their families, and the health care
      system, appropriate surveillance of such complex patterns can be a concern for
      birth defects registries. This paper provides examples of how monitoring of
      multiple anomalies can be beneficial from clinical and public health
      perspectives; presents a staged approach to documentation of such defects,
      including suggestions for their coding; describes the types of patterns in which
      they occur; and discusses some of the unique issues that arise with respect to
      statistical analysis of multiple versus isolated birth defects. 

PMID- 24893183
TI  - Using an existing birth defects surveillance program to enhance surveillance data
      on stillbirths.
AB  - BACKGROUND: Fetal death certificates (FDCs) are the main source of stillbirth
      surveillance data in the United States, yet previous studies suggest FDCs have
      incomplete ascertainment. In 2005, the Centers for Disease Control and Prevention
      (CDC) funded 2 pilot programs to determine the feasibility of expanding existing
      birth defects surveillance systems employing active casefinding methods to
      conduct surveillance of stillbirths. The objectives of this analysis were to: 1)
      estimate the completeness of ascertainment of stillbirths identified through one
      of the pilot programs, the Metropolitan Atlanta Congenital Defects Program
      (MACDP), and 2) compare the prevalence of stillbirths obtained through active
      casefinding (MACDP) with data available from FDCs. METHODS: Stillbirths in
      metropolitan Atlanta were independently ascertained by both FDC and MACDP in 2006
      and 2008. Capture-recapture methods were used to estimate the total number of
      stillbirths in the surveillance area. The sensitivities for capturing stillbirths
      were estimated for FDCs, MACDP, and both sources combined. Prevalence estimates
      for each data source and for the combined data sources were calculated using a
      denominator of live births plus FDC-identified stillbirths. RESULTS: An estimated
      1,118 stillbirths occurred in metropolitan Atlanta. MACDP captured 863 and FDCs
      captured 862. There were 198 stillbirths captured by MACDP and not reported by
      FDC, and 197 stillbirths identified by FDCs that were not initially captured by
      MACDP. The estimated sensitivities were 77.1 percent, 77.2 percent, and 94.8
      percent for FDCs, MACDP, and both sources combined, respectively. The stillbirth
      prevalences for 2006 and 2008 using FDC data alone were 8.2 and 7.4 per 1,000
      live births plus stillbirths, respectively, and 9.9 and 9.3 per 1,000 live births
      plus stillbirths, respectively, using both data sources combined. CONCLUSIONS:
      Leveraging the resources of existing birth defects surveillance programs in
      combination with FDCs could improve population-based ascertainment of
      stillbirths.

PMID- 24893184
TI  - An informatics-enabled approach for detection of new tumor registry cases.
AB  - Tumor registries are held to a very high standard for identifying and reporting
      new analytic cancer cases. However, current approaches to new case detection are
      often inefficient and costly. Efficient and effective detection of new cancer
      cases has the potential to maintain a high accuracy of reporting while reducing
      costs, increasing timeliness of reporting, and ultimately advancing cancer
      research. We describe the development, implementation, and evaluation of an
      informatics tool that integrates multiple data sources to support the workflow of
      new case identification at the Vanderbilt University Medical Center (VUMC) tumor
      registry office. The new system reduced the total number of potential cases to
      analyze from roughly 13,000 to 2,500 records per month. This resulted in an
      efficiency gain of roughly 80 man hours per month with a respective annual
      savings of approximately 50,000 dollars. Further iterative refinement of this
      approach along with support for case abstraction could result in further
      efficiencies. 

PMID- 24893185
TI  - Assessing the quality of race/ethnicity, tumor, and breast cancer treatment
      information in a non-SEER state registry.
AB  - INTRODUCTION: The quality of population-based cancer registries are largely
      defined by the completeness, accuracy, and timeliness of incident cases and
      demographics reported. However, both Surveillance, Epidemiology, and End Results
      (SEER) cancer registries and non-SEER population-based state cancer registries
      have been regularly used to examine treatment patterns. While the quality of
      treatment data in SEER cancer registries has often been examined and improved,
      the quality of such data in non-SEER state registries has rarely been assessed.
      METHODS: We used self-reported (SR) and medical record (MR) abstracted data from
      a population-based breast cancer study for comparison with information contained
      in the Illinois State Cancer Registry (registry). Using either MR or SR as the
      gold standard, we estimated concordance, kappa, and sensitivity for the presence
      or absence of surgery and initiation of chemotherapy, radiation and hormone
      therapy, as well as tumor characteristics, race/ethnicity and insurance status.
      RESULTS: The accuracy of most of the data elements examined was generally high.
      For instance, there was almost perfect agreement between SR race/ethnicity and
      registry documentation (k = 0.92). MR and registry data on tumor stage, grade,
      ER/PR status, and node status had substantial agreement (k = 0.78-0.88). In
      regard to treatment information, surgery was rarely underdocumented in registry
      data, while radiation and chemotherapy were modestly underdocumented (8 percent
      16 percent). On the other hand, per SR or MR, the registry generally failed to
      document hormonal treatment in a large proportion of cases (0.38 and 0.52,
      respectively). Health insurance information in the registry was also not well
      documented. There was only moderate agreement (k = 0.41) between SR and registry
      health insurance status, with uninsured patients being the least likely to be
      documented as such in the registry (sensitivity = 0.37 vs 0.96 and 0.63 for
      public and private insurance status, respectively). DISCUSSION: While some
      registry data elements are quite reliable, others warrant concern and must be
      interpreted with great caution. Understanding the strengths and limitations of a
      population-based non-SEER state cancer registry data can be useful to researchers
      who use these data sources to examine population cancer patterns or carry out
      cancer studies.

PMID- 24893187
TI  - A primer on molecular biology for certified tumor registrars.
AB  - Certified tumor registrars (CTRs) are expected to have expertise in cancer
      staging, treatment, and patient followup and an overall knowledge of the cancer
      disease process. As medicine becomes more personalized, the prognosis for
      individual cancer patients is beginning to include more molecular markers, and
      CTRs are being asked to record these results along with traditional anatomic
      information about the disease. Molecular markers, also called biomarkers, are
      measured using a variety of techniques, including fluorescent in situ
      hybridization (FISH), immunohistochemistry (IHC), enzyme-linked immunosorbent
      assay (ELISA), and reverse transcription polymerase chain reaction (RT-PCR). This
      primer will provide an overview of these techniques so that CTRs can more
      efficiently search medical records for information and more accurately record
      these data items into abstracting templates. 

PMID- 24893186
TI  - Economic evaluation of cancer registration in Europe.
AB  - BACKGROUND: Little has been reported on costs of cancer registration, and
      standard indicators have not yet been identified. This study investigated costs
      and outcomes of a sample of 18 European registries covering a population of 58.8
      million inhabitants. METHODS: Through a questionnaire, we asked registries for
      real cost data including personnel, information technology (IT), and
      infrastructure. Staff costs were grouped by professional position and by activity
      performed. As outcomes, besides the production of current data, we considered
      publications in peer-reviewed journals (last 5 years' impact factor [IF]) and
      characteristics of registry websites. RESULTS: In our sample, the average cost of
      cancer registration per inhabitant was ?0.27 at purchasing power standard (PPS)
      (range ?0.03-?0.97), while the mean cost per case registered was ?50.71 PPS
      (range ?6-?213). Personnel costs accounted for an average of 79 percent of total
      resources. Resources spent in routine activities (an average of 51 percent, range
      28 percent-87 percent) were predominant with respect to those allocated to
      research, with a few exceptions. Website quality seemed to be independent of
      total registry budget. CONCLUSIONS: The variance in costs of cancer registration
      across Europe can be attributed mainly to the type of registry (whether national
      or regional), the size of the covered population, and the national economic
      profile, expressed as gross domestic product.

PMID- 24893188
TI  - From trial and error to Equator Network.

PMID- 24893189
TI  - Identification of messenger RNA of fetoplacental source in maternal plasma of
      women with normal pregnancies and pregnancies with intrauterine growth
      restriction.
AB  - OBJECTIVE: to quantify placenta-specific RNA in plasma of women carrying foetuses
      with intrauterine growth restriction and pregnant women with normal pregnancies.
      METHODS: 8 pregnant women with foetuses with intrauterine growth restriction were
      studied as well as 18 women with uncomplicated pregnancies in the third pregnancy
      trimester. Total free RNA was quantified in maternal plasma by spectrophotometry
      and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA
      level through technical Real Time-Chain Reaction Polymerase. RESULTS: plasma RNA
      of fetoplacental origin was successfully detected in 100% of pregnant women.
      There were no statistically significant differences between the values of total
      RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL
      gene (p= 0.5785) between cases and controls. CONCLUSION: messenger RNA of
      fetoplacental origin can be detected in maternal plasma during pregnancy.

PMID- 24893190
TI  - Relationship between genotypes of the Duffy blood groups and malarial infection
      in different ethnic groups of Choco, Colombia.
AB  - INTRODUCTION: The negative homozygous condition for the Duffy blood group (Fy-/Fy
      ) confers natural resistance to Plasmodium vivax infection. Studies carried out
      in pursuing this direction in Colombia are scarce. OBJECTIVE: To describe the
      relationship between Duffy genotypes in three ethnic communities of La Italia
      (Choco) and malarial infection. METHODS: This is a descriptive, cross-sectional
      study in symptomatic and asymptomatic subjects with malaria. SAMPLE SIZE: Afro
      Colombians 73; Amerindian (Embera) 74, and Mestizo, 171. The presence of
      Plasmodium infection was assessed by thick smear and the status of the Duffy gene
      was studied by PCR and RFLP to help identify changes to T-46C and A131G which
      originate the genotypes T/T, T/C , C/C and G/G, G/A, A/A. RESULTS: Infection by
      Plasmodium was detected in 17% of cases with 62% due to P. falciparum and 27% due
      to P. vivax. Duffy genotypes were significantly associated with ethnicity (p=
      0.003). Individuals with the C/C, A/A diplotypes were exclusively infected by P.
      falciparum, whereas the other diplotypes were infected with either of the
      species. In the Amerindian and Mestizo populations, the frequency of the T-46
      allele was 0.90-1.00, among Afro-Colombians this was 0.50, the same as with the C
      allele and with an absence of heterozygous. At locus 131, the maximum frequency
      of the G allele was 0.30 in Amerindians and the maximum of the A allele was 0.69
      in Afro-Colombians. CONCLUSIONS: In the Amerindian and mestizo populations
      studied, there was a predominance of the allele T-46 (FY+) but this was not
      observed with the P. vivax infection. P. vivax was ruled out in all FY-
      individuals.

PMID- 24893191
TI  - Pilot study of hemoglobinopathies in newborns of the Rafael Calvo maternity
      clinic of Cartagena, Colombia.
AB  - INTRODUCTION: The hemoglobinopathies are a heterogeneous group of congenital
      anemias from Africa, Asia and the Mediterranean. Due to the migration of this
      population have spread worldwide, especially in Latin America and the Caribbean
      region, which Cartagena de Indias is included, with a large proportion of people
      of African descent. The lack of routine programs that include an appropriate
      methodology for precise identification of those affected and carriers, impossible
      to know the real behavior of this disease in our country and an early and
      appropriate to the patients before the disease manifests itself and produce its
      serious consequences. OBJECTIVE: To estimate the incidence and describe the
      epidemiological profile of hemoglobinopathies in newborns Rafael Calvo Maternity
      Clinic of Cartagena, in the period from January to June 2010. METHODS:
      Prospective descriptive study of a population of 1,729 newborns. Samples were
      collected cord blood on filter paper. Isoelectric focusing electrophoresis (IEF
      )was used to separate the haemoglobins. RESULTS: 94.4% (1,633 samples) were
      normal (hemoglobin FA), 4.5% (78 samples) were heterozygous for haemoglobin S
      (HbFAS), 1% (17samples) were heterozygous for haemoglobin C (hemoglobin FAC) and
      0.1% (1 sample) was double heterozygous SC (hemoglobin FSC). CONCLUSION: Due to
      the high incidence of hemoglobinopathies found in this pilot study highlights the
      importance and necessity of establishing an obligatory neonatal screening in the
      city of Cartagena, in order to make a timely diagnosis and monitoring of affected
      and carrier.

PMID- 24893192
TI  - Acute kidney injury applying pRifle scale in Children of Hospital Universitario
      del Valle in Cali, Colombia: clinical features, management and evolution.
AB  - OBJECTIVE: To know the epidemiology of Acute Kidney Injury (AKI) in the pediatric
      population at Hospital Universitario del Valle (HUV), a tertiary University
      Hospital in Cali, Colombia. METHODS: We obtained a series of cases through daily
      surveillance for a seven-month period (June 1 to December 31, 2009) in patients
      older than 30 days and under 18 years at HUV. We excluded patients with previous
      diagnosis of chronic renal failure. The new pRIFLE scale was used to define AKI.
      RESULTS: 27 patients were detected, with mean age of 36 months. Incidence of AKI
      was 0.38% from pediatric admissions and 6.2% from the pediatric intensive care
      unit (pICU) admissions. The pRIFLE scale at study entrance was: Risk: 2 patients,
      Injury: 8, Failure: 17. Etiology of AKI was: pre-renal in 89%, primary renal
      disease in 3.7%, and post-renal in 7.4%. There was an association of AKI with
      sepsis in 66.7% and 48.2% progressed to septic shock. Six patients required renal
      replacement therapy, all required peritoneal dialysis. The AKI was multi
      factorial in 59.3% and associated with systemic multi-organ failure in 59.3%. At
      study entry, 63% patients were in pICU. The average hospital stay was 21.3 +/-
      9.2 days. Six children died, 16 resolved AKI, and nine were left with renal
      sequelae. CONCLUSIONS: We recommended pRIFLE scale for early diagnosis of AKI in
      all pediatric services. Education in pRIFLE scale, prevention of AKI, and early
      management of sepsis and hypovolemia is recommended.

PMID- 24893193
TI  - Ecology and policy for exclusive breastfeeding in Colombia: a proposal.
AB  - INTRODUCTION: Breastfeeding promotion is one of the most important strategies
      against infant mortality and to control child undernourishment. Despite policies
      and plans to promote and protect breastfeeding in Colombia, its practice is low
      and its duration is short. OBJECTIVE: To propose an ecology framework to
      interpret and incorporate contextual, interpersonal, and individual factors
      associated with the practice of breastfeeding and duration. Thereby, the plans
      and policies addressed to promote and protect breastfeeding in Colombia could be
      reinforced. CONCLUSIONS: To implement an ecology framework for Breastfeeding in
      Colombia, it is necessary to identify the effect of contextual factors in the
      biggest cultural regions of Colombia, to recognize the limitations of Infant
      Friendly Hospital Initiatives to improve exclusive breastfeeding duration, to
      execute prospective studies in order to identify factors associated with
      breastfeeding duration, to design and implement plans and policies based on
      comprehensive planning strategies of healthcare interventions, to develop
      appropriate and cost-effective extra-institutional strategies aimed at prolonging
      the duration of breastfeeding, and to implement more reliable breastfeeding
      surveillance systems.

PMID- 24893194
TI  - Achondroplasia among ancient populations of mesoamerica and South America:
      Iconographic and Archaeological Evidence.
AB  - INTRODUCTION: Achondroplasia is the most frequent form of short-limb dwarfism.
      Affected individuals exhibit short stature caused by rhizomelic shortening of the
      limbs, characteristic facies with frontal bossing and mid-face hypoplasia, genu
      varum, and trident hand. Although the etiology of this disease was reported in
      1994, evidence of this disease in ancient populations has been found in
      populations of ancient Egypt (2500 BC) and it has been documented in ancient
      American populations. OBJECTIVE: To analyze the presence of individuals with
      achondroplasia in the Mayan state society of Mexico and Guatemala, during the
      Classical (100- 950 AC ) and Post-Classical (950 - 1519 AC ) periods; likewise,
      in the hierarchical-chieftain society of Tumaco-la Tolita (300 BC - 600 AC ) from
      the Colombia-Ecuador Pacific coast, and the Moche state society (100 - 600 AC )
      from the northern coast of Peru. METHODS: Iconographic and clinical-morphological
      studies of some of the most important artistic representations of individuals of
      short stature in these three cultures. CONCLUSION: We present the hypothesis that
      the individuals with short stature were somehow associated with the political and
      religious power elite.

PMID- 24893195
TI  - Correlation of anthropometric variables, conditional and exercise habits in
      activite olders.
AB  - OBJECTIVE: This study sought to correlate the anthropometric and functional
      variables, and exercise habits in a group of elderly adults who regularly attend
      exercise programs. METHOD: Participation of 217 subjects between 60 and 85 years
      of age, from 13 regions of Colombia. Anthropometric and functional assessment was
      conducted as a questionnaire on exercise habits. RESULTS: Negative correlations
      were shown between exercise habits and body fat and positive correlations between
      hand strength and VO2 max. (r = 0.4), age was negatively associated to functional
      variables. CONCLUSIONS: The functional capacity is influenced by increased age
      and body fat. With higher frequencies of physical exercise, VO2 max. and strength
      improved, but less body fat was observed.

PMID- 24893198
TI  - Lead poisoning due to bullets lodged in the human body.
AB  - With the increased violence and use of firearms in Colombia, we may see more
      cases of lead poisoning in our environment, and must be prepared to diagnose and
      treat them. Subtle signs and symptoms as unexplained anemia, gastro-intestinal
      discomfort and abdominal cramps, as well as severe signs such as changes in
      behavior and neurological status, nephropathy, and unexplained death, may be
      associated with a history of gunshot wounds and bullets in the human body. We
      must offer the patient knowledge and management strategies of pathology. 

PMID- 24893197
TI  - Nephrotic syndrome with a nephritic component associated with toxoplasmosis in an
      immunocompetent young man.
AB  - INTRODUCTION: Although the association of infection by toxoplasmosis with the
      development of nephrotic syndrome is uncommon, cases of this association have
      nevertheless been reported in the literature for more than two decades, not only
      for congenital toxoplasmosis, but also in acquired cases, and occasionally in
      immunocompetent patients. DEVELOPMENT: A case is presented of an immunocompetent
      patient aged 15 with clinical and laboratory indications of nephrotic/nephritic
      syndrome, in whom serological tests showed Toxoplasma infection. CONCLUSION: The
      presentation of nephrotic syndrome in ages where it is not commonly seen, leads
      to clinical suspicion of secondary causes. Active search for possible causes
      should include common tropical infections.

PMID- 24893196
TI  - Plasma cortisol activity in rats under conditions of chronic stress supplemented
      with resveratrol.
AB  - OBJECTIVE: To determine the activity of cortisol in rats treated with exogenous
      adrenocorticotropic hormone (ACTH) and a resveratrol supplement. METHODS: Forty
      eight adult female rats and 16 male rats of the strain (Rattus norvegicus) that
      were three months old and with body weights ranging from 200 to 250 g for females
      and 300 to 350 g for males were used and kept in controlled environmental
      conditions: temperature of 20+/-2 degrees  C and light-dark cycles of 14 and 10
      hours. They were fed a balanced diet and had free access to water. The rats were
      randomly divided into four groups: group 1 - was treated with 5 ug/kg of ACTH
      i.p. every twelve hours; group 2 - received the same treatment with ACTH plus a
      grape extract supplement (resveratrol) of 40 mg/kg; group 3 - only received grape
      extract (resveratrol); and group 4 - received a saline solution (0.9%) i.p. and
      oral, and served as controls. The experimental design was a 2*2 factorial with
      two levels ACTH and two polyphenol levels (grape extract). RESULTS: No
      significant differences were found in blood cortisol concentrations, by day and
      gender, or by treatment effects (0.75 ug/dL +/- 0.11; p <0.001). CONCLUSION:
      Results suggest that chronic stress and consumption of resveratrol did not
      directly alter levels of plasmatic cortisol in either stressed or unstressed
      rats. It was concluded that the given dosage levels of ACTH possibly did not
      produce sufficient stimulation of the adrenal gland for these animals.

PMID- 24893199
TI  - Role of AKT/mTORC1 pathway in pancreatic beta-cell proliferation.
AB  - Growth factors, insulin signaling and nutrients are important regulators of beta
      cell mass and function. The events linking these signals to regulation of beta
      cell mass are not completely understood. Recent findings indicate that mTOR
      pathway integrates signals from growth factors and nutrients with transcription,
      translation, cell size, cytoskeleton remodeling and mitochondrial metabolism.
      mTOR is a part of two distinct complexes; mTORC1 and mTORC2. The mammalian TORC1
      is sensitive to rapamycin and contains Raptor, deptor, PRAS40 and the G protein
      beta-subunit-like protein (GbetaL). mTORC1 activates key regulators of protein
      translation; ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E-binding
      protein 1. This review summarizes current findings about the role of AKT/mTORC1
      signaling in regulation of pancreatic beta cell mass and proliferation. mTORC1 is
      a major regulator of beta-cell cycle progression by modulation of cyclins D2, D3
      and cdk4/cyclin D activity. These studies uncovered key novel pathways
      controlling cell cycle progression in beta-cells in vivo. This information can be
      used to develop alternative approaches to expand beta-cell mass in vivo and in
      vitro without the risk of oncogenic transformation. The acquisition of such
      knowledge is critical for the design of improved therapeutic strategies for the
      treatment and cure of diabetes as well as to understand the effects of mTOR
      inhibitors in beta-cell function. 

PMID- 24893200
TI  - Efficient host-guest energy transfer in polycationic cyclophane-perylene diimide
      complexes in water.
AB  - We report the self-assembly of a series of highly charged supramolecular
      complexes in aqueous media composed of cyclobis(4,4'-(1,4-phenylene)bispyridine-p
      phenylene)tetrakis(chloride) (ExBox) and three dicationic perylene diimides
      (PDIs). Efficient energy transfer (ET) is observed between the host and guests.
      Additionally, we show that our hexacationic complexes are capable of further
      complexation with neutral cucurbit[7]uril (CB[7]), producing a 3
      polypseudorotaxane via the self-assembly of orthogonal recognition moieties.
      ExBox serves as the central ring, complexing to the PDI core, while two CB[7]s
      behave as supramolecular stoppers, binding to the two outer quaternary ammonium
      motifs. The formation of the 3-polypseudorotaxane results in far superior
      photophysical properties of the central PDI unit relative to the binary complexes
      at stoichiometric ratios. Lastly, we also demonstrate the ability of our binary
      complexes to act as a highly selective chemosensing ensemble for the
      neurotransmitter melatonin. 

PMID- 24893202
TI  - Position of acoustic stimulus modulates visual alpha activity.
AB  - It has been repeatedly shown that a unimodal stimulus can modulate oscillatory
      activity of multiple cortical areas already at early stages of sensory
      processing. In this way, an influence can be exerted on the response to a
      subsequent sensory input. Even though this fact is now well established, it is
      still not clear whether cortical sensory areas are informed about spatial
      positions of objects of modality other than their preferred one. Here, we test
      the hypothesis of whether oscillatory activity of the human visual cortex depends
      on the position of a unimodal auditory object. We recorded electroencephalogram
      while presenting sounds in an acoustic free-field either at the center of the
      visual field or at lateral positions. Using independent component analysis, we
      identified three cortical sources located in the visual cortex, showing stimulus
      position-specific oscillatory responses. The most pronounced effect was an
      immediate alpha (8-12 Hz) power decrease over the entire occipital lobe when the
      stimulus originated from the center of the binocular visual field. Following a
      lateral stimulation, the amplitude of alpha activity decreased slightly over
      contralateral visual areas, while at the same time a weak alpha synchronization
      was observed in corresponding ipsilateral areas. Thus, even in the absence of
      visual stimuli, the visual cortex is differentially activated depending on the
      position of an acoustic sound source. Our results show that the visual cortex
      receives information about the position of auditory stimuli within the visual
      field.

PMID- 24893201
TI  - Functional relationship between oxytocin and appetite for carbohydrates versus
      saccharin.
AB  - Centrally acting oxytocin (OT) inhibits feeding. Recent evidence suggests a link
      between OT and control of carbohydrate and saccharin intake, but it is unclear
      whether OT affects appetite for only carbohydrates, especially sweet ones, or
      sweet tastants irrespective of their carbohydrate content. Therefore, a blood
      brain barrier penetrant OT receptor antagonist, L-368,899, was administered in
      mice and intake of liquid diets containing carbohydrates sucrose, glucose,
      fructose, polycose, or cornstarch (CS) or the noncarbohydrate, noncaloric
      sweetener saccharin was studied in episodic intake paradigms: one in which only
      one tastant was available and the other in which a choice between a carbohydrate
      (sucrose, glucose, or fructose) and saccharin was provided. We also used real
      time PCR to examine hypothalamic Ot mRNA levels in mice provided short-term
      access to sucrose, CS, or saccharin. In the no-choice paradigm, L-368,899
      increased the intake of all carbohydrates, whereas its effect on saccharin
      consumption showed only a trend. A 10 times lower dose (0.3 mg/kg) stimulated
      intake of sucrose than other carbohydrates. In the choice test, a very low 0.1
      mg/kg dose of L-368,899 doubled the proportion of sucrose consumption relative to
      saccharin, but did not affect fructose or glucose preference. Ot gene expression
      increased after sucrose and CS, but not saccharin exposure compared with the
      controls; however, a higher level of significance was detected in the sucrose
      group. We conclude that OT inhibits appetite for carbohydrates. Sucrose
      consumption considerably enhances Ot gene expression and is particularly
      sensitive to OT receptor blockade, suggesting a special functional relationship
      between OT and sugar intake. 

PMID- 24893203
TI  - Disrupted daily light-dark cycles induce physical inactivity and enhance weight
      gain in mice depending on dietary fat intake.
AB  - We evaluated associations between obesity induced by a high-fat diet (HFD) and
      the environmental light-dark (LD) cycle that entrains the master circadian clock
      located in the suprachiasmatic nucleus of mammals. Mice were fed normal diet or
      HFD for 6 weeks in individual cages with running wheels under a normal 12 h light
      12 h dark cycle (LD 12 : 12) or an ultradian 3 h light-3 h dark cycle (LD 3 : 3)
      that might perturb the central clock. Circadian behavioral rhythms in mice fed
      both diets were disrupted by light-induced direct suppression of the behavior
      (masking effect) under LD 3 : 3. The ultradian LD cycle reduced the total daily
      activity of wheel running and enhanced body weight gain in the mice fed the HFD.
      Secondary effects such as obesity are probably not associated with inactivity
      induced under these circumstances because wheel-running activity decreased
      markedly within a few days of transfer from LD 12 : 12 to LD 3 : 3. Food
      consumption was significantly suppressed under LD 3 : 3 in mice fed the HFD.
      These findings suggest that the aberrant LD cycle induced physical inactivity and
      enhanced weight gain depending on dietary fat consumption. This might help to
      explain the higher incidence of obesity among shift workers.

PMID- 24893206
TI  - Sense and shoot: simultaneous detection and degradation of low-level contaminants
      using graphene-based smart material assembly.
AB  - Smart material nanoassemblies that can simultaneously sense and shoot low-level
      contaminants from air and water are important for overcoming the threat of
      hazardous chemicals. Graphene oxide (GO) sheets deposited on mesoscopic TiO2
      films that underpin the deposition of Ag nanoparticles with UV irradiation
      provide the foundation for the design of a smart material. The Ag particle size
      is readily controlled through precursor concentration and UV irradiation time.
      These semiconductor-graphene oxide-metal (SGM) films are SERS-active and hence
      capable of sensing aromatic contaminants such as 4-nitrobenzenethiol (4-NBT) in
      nanomolar range. Increased local concentration of organic molecules achieved
      through interaction with 2-D carbon support (GO) facilitates low-level detection
      of contaminants. Upon UV irradiation of 4-NBT-loaded SGM film, one can induce
      photocatalytic transformations. Thus, each component of the SGM film plays a
      pivotal role in aiding the detection and degradation of a contaminant dispersed
      in aqueous solutions. The advantage of using SGM films as multipurpose "detect
      and destroy" systems for nitroaromatic molecules is discussed.

PMID- 24893204
TI  - Characterization of the Zn(II) binding properties of the human Wilms' tumor
      suppressor protein C-terminal zinc finger peptide.
AB  - Zinc finger proteins that bind Zn(II) using a Cys2His2 coordination motif within
      a betabetaalpha protein fold are the most abundant DNA binding transcription
      factor domains in eukaryotic systems. These classic zinc fingers are typically
      unfolded in the apo state and spontaneously fold into their functional
      betabetaalpha folds upon incorporation of Zn(II). These metal-induced protein
      folding events obscure the free energy cost of protein folding by coupling the
      protein folding and metal-ion binding thermodynamics. Herein, we determine the
      formation constant of a Cys2His2/betabetaalpha zinc finger domain, the C-terminal
      finger of the Wilms' tumor suppressor protein (WT1-4), for the purposes of
      determining its free energy cost of protein folding. Measurements of individual
      conditional dissociation constants, Kd values, at pH values from 5 to 9 were
      determined using fluorescence spectroscopy by direct or competition titration.
      Potentiometric titrations of apo-WT1-4 followed by NMR spectroscopy provided the
      intrinsic pKa values of the Cys2His2 residues, and corresponding potentiometric
      titrations of Zn(II)-WT1-4 followed by fluorescence spectroscopy yielded the
      effective pKa(eff) values of the Cys2His2 ligands bound to Zn(II). The Kd, pKa,
      and pKa(eff) values were combined in a minimal, complete equilibrium model to
      yield the pH-independent formation constant value for Zn(II)-WT1-4, Kf(ML) value
      of 7.5 * 10(12) M(-1), with a limiting Kd value of 133 fM. This shows that Zn(II)
      binding to the Cys2His2 site in WT1-4 provides at least -17.6 kcal/mol in driving
      force to fold the protein scaffold. A comparison of the conditional dissociation
      constants of Zn(II)-WT1-4 to those from the model peptide Zn(II)-GGG-Cys2His2
      over the pH range 5.0 to 9.0 and a comparison of their pH-independent Kf(ML)
      values demonstrates that the free energy cost of protein folding in WT1-4 is less
      than +2.1 kcal/mol. These results validate our GGG model system for determining
      the cost of protein folding in natural zinc finger proteins and support the
      conclusion that the cost of protein folding in most zinc finger proteins is
      <=+4.2 kcal/mol, a value that pales in comparison to the free energy contribution
      of Zn(II) binding, -17.6 kcal/mol. 

PMID- 24893208
TI  - Synthesis, biological evaluation and molecular modeling study of pyrazole
      derivatives as selective COX-2 inhibitors and anti-inflammatory agents.
AB  - A novel series of pyrazole derivatives were synthesized and evaluated in vivo for
      their anti-inflammatory activity in carrageenan-induced rat paw edema model.
      Among all compounds, 5a, and 5b showed comparable anti-inflammatory activity to
      Nimesulide, the standard drug taken for the studies. In silico (docking) studies
      were carried out to investigate the theoretical binding mode of the compounds to
      target the cyclooxygenase (COX-2) using Autodock 4.2. 

PMID- 24893207
TI  - Suppression of hepatitis C virus replication by cyclin-dependent kinase
      inhibitors.
AB  - Hepatitis C virus (HCV) is a causative agent of chronic hepatitis. Although the
      standard therapy for HCV-infected patients consists of pegylated interferon plus
      ribavirin, this treatment is associated with serious side effects and high costs,
      and fails in some patients infected with specific HCV genotypes. To address this
      problem, we are developing small-molecule inhibitors of cyclin-dependent kinases
      (CDKs) as novel anti-HCV drug candidates. Previous data showed that HCV
      replication is inhibited by retinoblastoma protein, which is itself inactivated
      by CDK-mediated phosphorylation. Here, we report that CDK inhibitors suppress HCV
      replication in vitro and in vivo, and that CDK4 is required for efficient HCV
      replication. These findings shed light on the development of novel anti-HCV drugs
      that target host factors. 

PMID- 24893210
TI  - Theoretical reaction kinetics astride the transition between moderate and deep
      tunneling regimes: the F + HD case.
AB  - For the reaction between F and HD, giving HF + D and DF + H, the rate constants,
      obtained from rigorous quantum scattering calculations at temperatures ranging
      from 350 K down to 100 K, show deviations from the Arrhenius behavior that have
      been interpreted in terms of tunneling of either H or D atoms through a potential
      energy barrier. The interval of temperature investigated extends from above to
      below a crossover value Tc, a transition temperature separating the moderate and
      deep quantum tunneling regimes. Below Tc, the rate of the H or D exchange
      reaction is controlled by the prevalence of tunneling over the thermal activation
      mechanism. In this temperature range, Bell's early treatment of quantum
      tunneling, based on a semiclassical approximation for the barrier permeability,
      provides a reliable tool to quantitatively account for the contribution of the
      tunneling effect. This treatment is here applied for extracting from rate
      constants properties of the effective tunneling path, such as the activation
      barrier height and width. We show that this is a way of parametrizing the
      dependence of the apparent activation energy on temperature useful for both
      calculated and experimental rate constants in an ample interval of temperature,
      from above to below Tc, relevant for modelization of astrophysical and in general
      very low-temperature environments. 

PMID- 24893209
TI  - Let's talk about health: shoppers' discourse regarding health while food
      shopping.
AB  - OBJECTIVE: The present study aimed to examine the role of health in consumers'
      food purchasing decisions through investigating the nature of people's discourse
      regarding health while conducting their food shopping. DESIGN: The study employed
      the think-aloud technique as part of an accompanied shop. All mentions of health
      and terms relating to health were identified from the data set. Inductive
      thematic analysis was conducted to examine how health was talked about in
      relation to people's food choice decisions. SETTING: Supermarkets in Dublin,
      Republic of Ireland and Belfast, Northern Ireland. SUBJECTS: Participants (n 50)
      were aged over 18 years and represented the main household shopper. RESULTS:
      Responsibility for others and the perceived need to illicit strict control to
      avoid 'unhealthy' food selections played a dominant role in how health was talked
      about during the accompanied shop. Consequently healthy shopping was viewed as
      difficult and effort was required to make the healthy choice, with shoppers
      relating to product-based inferences to support their decisions. CONCLUSIONS:
      This qualitative exploration has provided evidence of a number of factors
      influencing the consideration of health during consumers' food shopping. These
      results highlight opportunities for stakeholders such as public health bodies and
      the food industry to explore further ways to help enable consumers make healthy
      food choices.

PMID- 24893205
TI  - Epoxyeicosatrienoic acids and cardioprotection: the road to translation.
AB  - Cardiovascular disease, including acute myocardial infarction (AMI), is the
      leading cause of morbidity and mortality globally, despite well-established
      treatments. The discovery and development of novel therapeutics that prevent the
      progression of devastating consequences following AMI are thus important in
      reducing the global burden of this devastating disease. Scientific evidence for
      the protective effects of epoxyeicosatrienoic acids (EETs) in the cardiovascular
      system is rapidly emerging and suggests that promoting the effects of these
      cytochrome P450-derived epoxyeicosanoids is a potentially viable clinical
      therapeutic strategy. Through a translational lens, this review will provide
      insight into the potential clinical utility of this therapeutic strategy for AMI
      by 1) outlining the known cardioprotective effects of EETs and underlying
      mechanisms demonstrated in preclinical models of AMI with a particular focus on
      myocardial ischemia-reperfusion injury, 2) describing studies in human cohorts
      that demonstrate a relationship between EETs and associated pathways with
      coronary artery disease risk, and 3) discussing preclinical and clinical areas
      that require further investigation in order to increase the probability of
      successfully translating this rapidly emerging body of evidence into a clinically
      applicable therapeutic strategy for AMI. 

PMID- 24893212
TI  - Characterization of cyclodextrin containing nanofilters for removal of
      pharmaceutical residues.
AB  - Due to the increasing amount of persistent organic pollutants (POPs) in general
      and pharmaceutical residues in particular in municipal wastewater, the efficiency
      of water treatment technologies should be improved. Following the biological
      treatment of wastewater nanofiltration offers a possible way for the removal of
      POPs. In this study beta-cyclodextrin containing nanofilters having different
      chemical composition and thickness (1.5-3.5mm) were investigated. For their
      characterization, their adsorption capacity was determined applying ibuprofen
      containing model solution and total organic carbon (TOC) analyzer. It could be
      established that the regeneration of nanofilters with ethanol and the application
      of inorganic additives (NaCl, NaHCO3, NH4HCO3) increased the adsorption capacity
      of nanofilters. The best results were achieved with chemical composition of
      30m/m% beta-cyclodextrin polymer beads and 70m/m% ultra-high molecular weight
      polyethylene in the presence of 12mmol ammonium hydrogen carbonate/nanofilter. 

PMID- 24893211
TI  - Metabolomic study of raw and processed Atractylodes macrocephala Koidz by LC-MS.
AB  - Bai-Zhu, the dried rhizome of Atractylodes macrocephala Koidz (AMK), is widely
      used as a tonic herbal in eastern Asia. It is commonly used as prepared slices in
      clinic by stir-frying with wheat bran (processed AMK). In the theories of
      traditional Chinese medicine (TCM), Bai-Zhu possesses significantly different
      therapeutic effects before and after processing. However, the molecular mechanics
      of this processing is still unknown. In this paper, the strategy of metabolomics
      was employed to investigate the changes of chemical constituents in Atractylodes
      macrocephala Koidz after processing. Meanwhile, the cell activity test variation
      of processed and unprocessed medicine was used to interpret the processing
      mechanism of AMK. Using ultra-performance liquid chromatography quadrupole time
      of flight mass spectrometry (UPLC-QTOF/MS) with the method of multivariate
      statistic analyses including principal component analysis (PCA) and partial least
      square-discriminant analysis (PLS-DA), atractylenolide I, atractylenolide II,
      atractylenolide III, atractylenolide VI, 7-hydroxycoumarin, 8-beta-methoxy
      atractylenolide I and Selina-4 (14), 7 (11)-dien-8-one were rapidly explored as
      the potential chemical markers of raw and processed AMK, respectively.
      Furthermore, it could be speculated that the processing mechanism of AMK was to
      increase the content of atractylenolide III which could strengthen the effect on
      gastrointestinal function. 

PMID- 24893213
TI  - Visible light activated ion sensing using a photoacid polymer for calcium
      detection.
AB  - Presented here is a sensing membrane consisting of a modified merocyanine
      photoacid polymer and a calcium ionophore in plasticized poly(vinyl chloride).
      This membrane is shown to actively exchange protons with calcium ions when
      switched ON after illumination at 470 nm, and the exchange can be followed by UV
      vis spectroscopy. The sensing membrane shows no response in the ON state when
      calcium ions are absent. The limit of detection of the sensor is 5.0 * 10(-4) M
      with an upper detection limit of 1.0 M. Thus, we demonstrate for the first time
      the use of a visible light activated, lipophilic photoacid polymer in an ion
      sensing membrane for calcium ions, which highly discriminates potassium, sodium,
      and magnesium ions. 

PMID- 24893215
TI  - Review of the quality of observational studies of the association between
      rosiglitazone and acute myocardial infarction.
AB  - BACKGROUND: Following the publication of a meta-analysis reporting a risk of
      acute myocardial infarction (AMI) with rosiglitazone that led to severe
      restrictions being placed on its use, several observational studies of the
      association were reported. The lifting of restrictions in the United States in
      2013 makes a review of these studies pertinent. OBJECTIVE: To evaluate the
      quality of population-based observational studies of the rosiglitazone-AMI
      association. METHODS: PubMed and Embase literature databases were searched for
      observational studies evaluating the association that were published between 2006
      and 2010. Publications satisfying the inclusion criteria were reviewed using the
      Checklist for Retrospective Database Studies. RESULTS: Nineteen studies satisfied
      the inclusion criteria. Reasons for the research design and data source were
      absent or unclear in 18 (95%) and 16 (84%), respectively. Administrative data
      were used exclusively in 14 (74%). Baseline periods for prior diagnoses and
      medications varied widely. Reimbursement constraints on rosiglitazone use were
      reported in only seven studies (37%), although all were likely to have been
      impacted by them. What was being tested in half of the rosiglitazone treatment
      comparisons lacked specificity and clarity. All relied on risk ratios and, for
      90% of the comparisons, the ratios were between 0.5 and two - a level at which
      residual confounding can lead to spurious significance. CONCLUSION: Important
      deficiencies existed in the rosiglitazone studies suggesting that standards for
      methods and reporting of observational safety analyses need improvement. In
      particular, detailed clinical data should be included when the risk of
      confounding by indication is likely to be high.

PMID- 24893214
TI  - Differential effects of proteins and carbohydrates on postprandial blood pressure
      related responses.
AB  - Diet composition may affect blood pressure (BP), but the mechanisms are unclear.
      The aim of the present study was to compare postprandial BP-related responses to
      the ingestion of pea protein, milk protein and egg-white protein. In addition,
      postprandial BP-related responses to the ingestion of maltodextrin were compared
      with those to the ingestion of sucrose and a protein mix. We hypothesised that
      lower postprandial total peripheral resistance (TPR) and BP levels would be
      accompanied by higher plasma concentrations of nitric oxide, insulin, glucagon
      like peptide 1 (GLP-1) and glucagon. On separate occasions, six meals were tested
      in a randomised order in forty-eight overweight or obese adults with untreated
      elevated BP. Postprandial responses of TPR, BP and plasma concentrations of
      insulin, glucagon, GLP-1 and nitrite, nitroso compounds (RXNO) and S
      nitrosothiols (NO(x)) were measured for 4 h. No differences were observed in TPR
      responses. Postprandial BP levels were higher after the ingestion of the egg
      white-protein meal than after that of meals containing the other two proteins
      (P<= 0.01). The ingestion of the pea-protein meal induced the highest NO(x)
      response (P<= 0.006). Insulin and glucagon concentrations were lowest after the
      ingestion of the egg-white-protein meal (P<= 0.009). Postprandial BP levels were
      lower after the ingestion of the maltodextrin meal than after that of the protein
      mix and sucrose meals (P<= 0.004), while postprandial insulin concentrations were
      higher after the ingestion of the maltodextrin meal than after that of the
      sucrose and protein mix meals after 1-2 h (P<= 0.0001). Postprandial NO(x), GLP-1
      and glucagon concentrations were lower after the ingestion of the maltodextrin
      meal than after that of the protein mix meal (P<= 0.008). In conclusion,
      different protein and carbohydrate sources induce different postprandial BP
      related responses, which may be important for BP management. Lower postprandial
      BP levels are not necessarily accompanied by higher NO(x), insulin, glucagon or
      GLP-1 responses.

PMID- 24893216
TI  - Profiling of glucosinolates and flavonoids in Rorippa indica (Linn.) Hiern.
      (Cruciferae) by UHPLC-PDA-ESI/HRMS(n).
AB  - An UHPLC-PDA-ESI/HRMS(n) profiling method was used to identify the glucosinolates
      and flavonoids of Rorippa indica (Cruciferae), a wild vegetable and Chinese herb
      used to treat cough, diarrhea, and rheumatoid arthritis. Thirty-three
      glucosinolates, more than 40 flavonol glycosides, and 18 other phenolic and
      common organic compounds were identified. The glucosinolates and polyphenols were
      separated by UHPLC. High-resolution deprotonated molecules provided high accuracy
      mass values that were used to determine formulas and provide putative
      identification of the glucosinolates and flavonoids. The fragments from
      multistage mass spectrometry were used to elucidate the structures. The
      concentrations of the main components were based on UV peak areas and molar
      relative response factors with a single calibration standard. This study found
      this plant to be a rich source for glucosinolates, containing 24 new
      glucosinolates, including 14 glucosylated glucosinolates that were previously
      unidentified.

PMID- 24893218
TI  - Pigeons' tracking of relevant attributes in categorization learning.
AB  - Most theories and experimental investigations of discrimination learning and
      categorization, in both humans and animals, hypothesize that attention must be
      allocated to the relevant attributes of the training stimuli for learning to
      occur. Attention has conventionally been inferred after learning has transpired
      rather than examined while learning is transpiring. We presented pigeons with a
      visual categorization task in which we monitored their choice accuracy through
      their responses to different report buttons; critically, we tracked the location
      of the pigeons' pecks to both the relevant and irrelevant attributes of the
      training stimuli using touchscreen technology, in order to find out where the
      birds may have been attending during the course of categorization learning.
      Pigeons readily mastered the categorization task; most importantly, as training
      progressed, they increasingly concentrated their pecks on the relevant features
      of the category exemplars, suggesting that the birds were tracking the relevant
      information to solve the task. When either new irrelevant features were
      introduced (Experiment 1) or when new relevant features were introduced and later
      the discriminative value of these new relevant features was reversed (Experiment
      2), pigeons' choice accuracy and peck tracking were strongly affected. These
      results help elucidate the dynamics and interplay of attention and learning; they
      also suggest that peck tracking can be a suitable measure of the allocation of
      attention in pigeons, much as eyetracking is deemed to be a suitable measure of
      attention in humans.

PMID- 24893217
TI  - Visual search and attention in blue jays (Cyanocitta cristata): Associative cuing
      and sequential priming.
AB  - Visual search for complex natural targets requires focal attention, either cued
      by predictive stimulus associations or primed by a representation of the most
      recently detected target. Because both processes can focus visual attention,
      cuing and priming were compared in an operant search task to evaluate their
      relative impacts on performance and to determine the nature of their interaction
      in combined treatments. Blue jays were trained to search for pairs of alternative
      targets among distractors. Informative or ambiguous color cues were provided
      before each trial, and targets were presented either in homogeneous blocked
      sequences or in constrained random order. Initial task acquisition was
      facilitated by priming in general, but was significantly retarded when targets
      were both cued and primed, indicating that the two processes interfered with each
      other during training. At asymptote, attentional effects were manifested mainly
      in inhibition, increasing latency in miscued trials and decreasing accuracy on
      primed trials following an unexpected target switch. A combination of cuing and
      priming was found to interfere with performance in such unexpected trials,
      apparently a result of the limited capacity of working memory. Because the
      ecological factors that promote priming or cuing are rather disparate, it is not
      clear whether they ever simultaneously contribute to natural predatory search.

PMID- 24893219
TI  - The role of local, distal, and global information in latent spatial learning.
AB  - In 4 experiments that investigated latent spatial learning, rats were repeatedly
      placed on a submerged platform in a corner of a square swimming pool with walls
      of different brightness. When they were subsequently released into the pool for a
      test trial in the absence of the platform, they spent the majority of time in the
      corner used for placement training-the correct corner. This effect was observed
      in Experiment 1, even when the test trial took place in a transformed version of
      the training arena. Experiments 2 and 3 indicated that the correct corner was
      identified by local cues based on the walls creating the corner. Experiment 4
      demonstrated that distal cues created by the two walls that did not surround the
      platform during placement training could also be used to identify the correct
      corner. There was no evidence of learning about the relationship between global
      cues provided by the entire arena and the goal. The absence of the opportunity to
      develop instrumental, stimulus-response associations during placement training
      indicates that stimulus-stimulus associations acquired during this training were
      sufficient to guide rats to the platform when they were eventually released into
      the pool.

PMID- 24893220
TI  - Rats respond for information: Metacognition in a rodent?
AB  - In 2 experiments, rats were trained to press a centrally located lever that
      delivered immediate food reinforcement and turned on a light signal that
      indicated the location of a further food reward. After rats learned to press the
      lever and use the light cue to find food, immediate reinforcement for lever
      pressing was discontinued. In Experiment 1, rats continued to press the lever for
      information about the location of reward in a T-maze, but control groups yoked to
      the experimental group for amount of reward, and conditioned reinforcement showed
      complete extinction of lever pressing. Rats tested on an 8-arm radial maze in
      Experiment 2 also continued to press a lever that did not yield immediate
      reinforcement but provided a light cue indicating which randomly chosen arm of
      the maze contained food; lever pressing declined significantly, however, when the
      same arm contained food on every trial. Comparisons of testing conditions between
      and within experiments suggested that probability of lever pressing increased as
      the amount of information gained increased. The comparative implications of these
      findings for metacognition are discussed.

PMID- 24893221
TI  - Serial block-face scanning electron microscopy for three-dimensional analysis of
      morphological changes in mitochondria regulated by Cdc48p/p97 ATPase.
AB  - Cdc48p is a highly conserved cytosolic AAA chaperone that is involved in a wide
      range of cellular processes. It consists of two ATPase domains (D1 and D2), with
      regulatory regions at the N- and C-terminals. We have recently shown that Cdc48p
      regulates mitochondrial morphology, in that a loss of the ATPase activity or
      positive cooperativity in the D2 domain leads to severe fragmentations and
      aggregations of mitochondria in the cytoplasm. We have now used serial block-face
      scanning electron microscopy (SBF-SEM), an advanced three-dimensional (3D)
      electron microscopic technique to examine the structures and morphological
      changes of mitochondria in the yeast Saccharomyces cerevisiae. We found that
      mutants lacking ATPase activity of Cdc48p showed mitochondrial fragmentations and
      aggregations, without fusion of the outer membrane. This suggests that the ATPase
      activity of Cdc48p is necessary for fusion of the outer membranes of
      mitochondria. Our results also show that SBF-SEM has considerable advantages in
      morphological and quantitative studies on organelles and intracellular structures
      in entire cells.

PMID- 24893222
TI  - Preparation and enzymatic degradation of porous crosslinked polylactides of
      biomass origin.
AB  - To understand the enzymatic degradation behavior of crosslinked polylactide
      (PLA), the preparation and enzymatic degradation of both thermoplastic (linear)
      and crosslinked PLAs that have pore structures with different dimensions were
      carried out. The porous structures of the linear PLA samples were of micro and
      nanoporous nature, and prepared by batch foaming with supercritical CO2 and
      compared with the porous structures of crosslinked PLA (Lait-X) created by the
      salt leaching method. The surface and cross-sectional morphologies of the porous
      structures were investigated by using scanning electron microscopy. The
      morphological analysis of porous Lait-X showed a rapid loss of physical features
      within 120 h of exposure to proteinase-K enzymatic degradation at 37  degrees C.
      Due to the higher affinity for water, enhanced enzymatic activity as compared to
      the linear PLA porous structures in the micro and nanoporous range was observed. 

PMID- 24893231
TI  - A systemic issue.

PMID- 24893224
TI  - Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus
      Preussia typharum.
AB  - Two new dimeric epipolythiodiketopiperazines, preussiadins A (1) and B (2),
      together with two known diastereomers, leptosins C (6) and A (7), were obtained
      from the mycelia of a Preussia typharum isolate. The structures of the new
      compounds were established by spectroscopic methods, and the absolute
      configurations of 1 and 2 were assigned by chemical transformations and
      comparisons of quantum chemical ECD and VCD calculations to experimental data.
      Compound 1 exhibited potent cytotoxic activity in the NCI-60 cell line panel with
      an average LC50 value of 251 nM. Further studies demonstrated that 1 circumvents
      P-glycoprotein-mediated drug resistance, yet had no significant antitumor
      activity in a xenograft UACC-62 melanoma model. 

PMID- 24893223
TI  - Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity.
AB  - Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic
      treatment of Alzheimer's disease and other dementias. More recent use is for
      myasthenia gravis. Many of these inhibitors interact with the second known
      cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that
      acetylcholine plays a role in suppression of cytokine release through a
      "cholinergic anti-inflammatory pathway" which raises questions about the role of
      these inhibitors in the immune system. This review covers research and discussion
      of the role of the inhibitors in modulating the immune response using as examples
      the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and
      pyridostigmine. Major attention is given to the cholinergic anti-inflammatory
      pathway, a well-described link between the central nervous system and terminal
      effector cells in the immune system. 

PMID- 24893232
TI  - Neuromuscular complications of diabetes mellitus.
AB  - PURPOSE OF REVIEW: Diabetes mellitus has become a modern global epidemic, with
      steadily increasing prevalence rates related to lifestyle such that 27% of
      individuals aged 65 years or older have diabetes mellitus, 95% of whom have type
      2. This article reviews the effects of diabetes mellitus on the neuromuscular
      system. RECENT FINDINGS: Diabetes mellitus leads to diverse forms of peripheral
      neuropathy as the major neuromuscular complication. Both focal and diffuse types
      of neuropathy can develop, with the most common form being diabetic sensorimotor
      polyneuropathy. Small fibers are damaged early in the development of diabetic
      sensorimotor polyneuropathy and are not assessed by nerve conduction studies.
      Small fiber damage occurs even in the prediabetes stage. No disease-modifying
      therapy for diabetic sensorimotor polyneuropathy is available at this time, but
      this complication can be limited in patients who have type 1 diabetes mellitus
      with strict glycemic control; the same outcome is not clearly observed in
      patients who have type 2 diabetes mellitus. Recently, the evidence base for
      symptomatic treatments of painful diabetic sensorimotor polyneuropathy underwent
      systematic review. Effective evidence-based treatments include some
      anticonvulsants (eg, pregabalin, gabapentin), antidepressants (eg, amitriptyline,
      duloxetine), opioids (eg, morphine sulfate, oxycodone), capsaicin cream, and
      transcutaneous electrical nerve stimulation. SUMMARY: This article reviews the
      increasing prevalence of diabetes mellitus and diabetic sensorimotor
      polyneuropathy and discusses recent consensus opinion on the objective
      confirmation needed for the diagnosis in the clinical research setting. The
      evidence from clinical trials shows that intensive glycemic control reduces
      prevalence of diabetic sensorimotor polyneuropathy in patients with type 1
      diabetes mellitus, but variable outcomes are observed in patients with type 2
      diabetes mellitus. Finally, despite the lack of disease-modifying treatment,
      effective evidence-based therapy can control painful symptoms of diabetic
      sensorimotor polyneuropathy.

PMID- 24893233
TI  - Neurosarcoidosis.
AB  - PURPOSE OF REVIEW: This article provides an update on the evaluation and
      treatment of neurosarcoidosis. RECENT FINDINGS: The broad range of clinical
      manifestations of neurosarcoidosis has recently expanded to include painful small
      fiber neuropathy. Although definitive diagnosis remains a challenge,
      fluorodeoxyglucose positron emission tomographic (FDG-PET) scan and high
      resolution CT allow for improved detection of systemic sarcoidosis. In addition,
      endobronchial ultrasound-guided transbronchial needle aspiration provides a less
      invasive means of tissue confirmation of systemic sarcoidosis than
      mediastinoscopy. Although not standardized, treatment strategies for
      neurosarcoidosis now commonly include tumor necrosis factor-alpha antagonists in
      combination with corticosteroids and other cytotoxic agents for patients with
      severe disease. SUMMARY: Advances in the diagnosis and management of
      neurosarcoidosis may benefit the patient and clinician faced with this
      multifaceted disease.

PMID- 24893225
TI  - Making healthy eating and physical activity policy practice: the design and
      overview of a group randomized controlled trial in afterschool programs.
AB  - National and state organizations have developed policies calling upon afterschool
      programs (ASPs, 3-6 pm) to serve a fruit or vegetable (FV) each day for snack,
      while eliminating foods and beverages high in added-sugars, and to ensure
      children accumulate a minimum of 30 min/d of moderate-to-vigorous physical
      activity (MVPA). Few efficacious and cost-effective strategies exist to assist
      ASP providers in achieving these important public health goals. This paper
      reports on the design and conceptual framework of Making Healthy Eating and
      Physical Activity (HEPA) Policy Practice in ASPs, a 3-year group randomized
      controlled trial testing the effectiveness of strategies designed to improve
      snacks served and increase MVPA in children attending community-based ASPs.
      Twenty ASPs, serving over 1800 children (6-12 years) will be enrolled and match
      paired based on enrollment size, average daily min/d MVPA, and days/week FV
      served, with ASPs randomized after baseline data collection to immediate
      intervention or a 1-year delayed group. The framework employed, STEPs (Strategies
      To Enhance Practice), focuses on intentional programming of HEPA in each ASPs'
      daily schedule, and includes a grocery store partnership to reduce price barriers
      to purchasing FV, professional development training to promote physical activity
      to develop core physical activity competencies, as well as ongoing technical
      support/assistance. Primary outcome measures include children's accelerometry
      derived MVPA and time spend sedentary while attending an ASP, direct observation
      of staff HEPA promoting and inhibiting behaviors, types of snacks served, and
      child consumption of snacks, as well as, cost of snacks via receipts and detailed
      accounting of intervention delivery costs to estimate cost-effectiveness.

PMID- 24893234
TI  - Neurologic complications of nondiabetic endocrine disorders.
AB  - PURPOSE OF REVIEW: This article provides an overview of the neurologic
      complications found in the various endocrine disorders affecting adult patients.
      Specifically, disorders in pituitary hormones (prolactin, growth hormone,
      vasopressin, and oxytocin), thyroid hormones, adrenal hormones (glucocorticoids),
      and sex hormones (estrogen and testosterone) will be covered, with an emphasis on
      identifying the signs and symptoms in addition to diagnosing and managing these
      disorders. RECENT FINDINGS: Hyperthyroidism in the young was found to increase
      the risk for ischemic stroke in a recent prospective case-cohort study. The
      cognitive effects of hormonal therapy in postmenopausal women remain
      controversial, but a recent study found no benefit or risk in cognitive function
      when treating younger (50 to 55 years of age) postmenopausal women with hormonal
      therapy. SUMMARY: Endocrine disorders can cause various neurologic complications,
      from insidious myopathy to acute encephalopathy. Diagnosing the endocrine
      disorder as the cause of the neurologic impairment is essential, as treating the
      underlying hormonal dysfunction will often rapidly reverse the neurologic
      symptoms. Ongoing research is needed to further clarify the role of hormonal
      dysfunction in neurologic disorders.

PMID- 24893235
TI  - Neurologic complications of bariatric surgery.
AB  - PURPOSE OF REVIEW: The increasing utilization of bariatric surgery has been
      accompanied by an increased incidence and awareness of related neurologic
      complications. The purpose of this review is to provide up-to-date information on
      the neurologic complications related to bariatric surgery. RECENT FINDINGS:
      Neurologic complications related to bariatric surgery are predominantly due to
      nutrient deficiencies. Common early complications include Wernicke encephalopathy
      due to thiamine deficiency, and late complications include myelopathy or
      myeloneuropathy due to vitamin B12 or copper deficiency. SUMMARY: Early
      recognition and prompt institution of treatment is essential to prevent long-term
      disability. Often, life-long supplementation may be required.

PMID- 24893236
TI  - Neurologic complications of sepsis.
AB  - PURPOSE OF REVIEW: This article reviews the current understanding of sepsis, a
      critical and often fatal illness that results from infection and multiorgan
      failure and impacts the brain, peripheral nervous system, and muscle. RECENT
      FINDINGS: Encephalopathy occurs early in association with sepsis, and its
      severity correlates with mortality. Neuroimaging in patients with CNS
      manifestations is typically normal. EEG is nonspecific. EMG is commonly
      diagnostic, showing a combination of nerve and muscle injury already early in the
      clinical course. Rapid recognition and correction of reversible causes of
      encephalopathy and avoidance of risk factors for intensive care unit-acquired
      weakness may limit sequelae. Major deficiencies in our understanding of the
      complications of sepsis remain. Studies to improve the recognition and
      rehabilitation of these patients are imperative in a clinical syndrome affecting
      countless patients each year. SUMMARY: The risk of later cognitive and physical
      disability may be increased after sepsis; therefore, attention to neurologic
      complications is urgent.

PMID- 24893237
TI  - Acute symptomatic seizures and systemic illness.
AB  - PURPOSE OF REVIEW: This article addresses the occurrence of acute symptomatic
      seizures in the setting of many medical illnesses. RECENT FINDINGS: Many medical
      illnesses can cause seizures. Metabolic derangements, such as disorders of serum
      glucose metabolism, cause seizures, as well as other neurologic manifestations.
      Many medicines (such as antibiotics, antivirals, antidepressants, and
      antipsychotics), whether used at typical doses or in overdosage, can lead to
      acute symptomatic seizures. SUMMARY: Acute symptomatic seizures occur most often
      in illnesses that directly injure the brain. Trauma, stroke, CNS tumors, and CNS
      infection very commonly cause seizures. However, many medical illnesses do not
      directly injure the brain but lead to neurologic signs and symptoms, such as
      seizures. Recognizing these effects, especially in critically ill patients, is
      important for optimizing medical care.

PMID- 24893238
TI  - Neurologic complications of alcoholism.
AB  - PURPOSE OF REVIEW: This review serves as an overview of neurologic conditions
      associated with alcohol abuse or withdrawal, including epidemiology, clinical
      symptoms, diagnostic approach, and treatment. RECENT FINDINGS: Frequent alcohol
      abuse and frank alcoholism are very common among adults in the United States.
      Although rates decline with each decade, as many as 10% of the elderly drink
      excessively. Given the ubiquitous nature of alcoholism in society, its
      complications have been clinically recognized for generations, with recent
      advances focusing on improved understanding of ethanol's biochemical targets and
      the pathophysiology of its complications. SUMMARY: The chronic effects of alcohol
      abuse are myriad and include neurologic complications through both direct and
      indirect effects on the central and peripheral nervous systems. These disorders
      include several encephalopathic states related to alcohol intoxication,
      withdrawal, and related nutritional deficiencies; acute and chronic toxic and
      nutritional peripheral neuropathies; and myopathy. Although prevention of
      alcoholism and its neurologic complications is the optimal strategy, this article
      reviews the specific treatment algorithms for alcohol withdrawal and its related
      nutritional deficiency states.

PMID- 24893239
TI  - Neurologic complications of illicit drug abuse.
AB  - PURPOSE OF REVIEW: This review familiarizes clinicians with the symptoms of
      overdose and withdrawal, as well as neurologic complications, associated with
      particular illicit drugs. RECENT FINDINGS: Recent arrivals on the recreational
      drug scene include synthetic cathinone analogs, synthetic cannabinoid agonists,
      and a variety of novel hallucinogens. SUMMARY: Clinicians need to be aware of
      neurologic disorders associated with particular illicit drugs and should consider
      drug abuse in any patient with unexplained symptoms and signs.In addition to
      tobacco and alcohol, a large number of substances, legal and illegal, are used
      recreationally. Broad categories include opioids, psychostimulants, marijuana and
      related agents, sedatives, hallucinogens, inhalants, phencyclidine and related
      agents, and anticholinergics. Each type of agent has its own characteristic
      symptoms of overdose and withdrawal, and many agents are associated with trauma,
      infection, seizures, stroke, cognitive impairment, and teratogenicity. Some drugs
      have unique neurologic complications not encountered with other agents. A history
      of recreational drug use should be sought in any neurologic patient regardless of
      age or socioeconomic status.

PMID- 24893240
TI  - Neurologic complications of rheumatic disease.
AB  - PURPOSE OF REVIEW: This article discusses the specific neurologic issues that
      arise in patients with rheumatic diseases such as rheumatoid arthritis, systemic
      lupus erythematosus, and Sjogren syndrome. Diagnosis and management are
      discussed. RECENT FINDINGS: Advances include advanced imaging, serologic and CSF
      markers, and targeted immune-modulating therapies. The use of these modalities
      are discussed in detail. SUMMARY: Rheumatic disorders are quite common and can
      result in disabling but many times treatable neurologic sequelae. The key is
      early diagnosis and management. Awareness of the common presentations and current
      modalities of diagnosis and treatment is critical to improved outcomes.

PMID- 24893241
TI  - Neurologic manifestations of acute and chronic liver disease.
AB  - PURPOSE OF REVIEW: This article summarizes the most common neurologic sequelae of
      acute and chronic liver failure, liver transplantation, and other treatments for
      liver disease, and outlines the pathogenesis, neurologic manifestations, and
      treatment of Wilson disease. RECENT FINDINGS: The neurologic manifestations of
      liver disease are caused by the liver's failure to detoxify active compounds that
      have deleterious effects on the central and peripheral nervous systems. In
      addition, treatments for liver disease such as liver transplantation,
      transjugular intrahepatic portosystemic shunt, and antiviral medications can also
      be neurotoxic. Wilson disease affects the liver and nervous system simultaneously
      and may often initially be diagnosed by a neurologist; treatment options have
      evolved over recent years. SUMMARY: Acute and chronic liver diseases are
      encountered commonly in the general population. Neurologic dysfunction will
      eventually affect a significant number of these individuals, especially if the
      disease progresses to liver failure. Early recognition of these neurologic
      manifestations can lead to more effective management of these patients.

PMID- 24893243
TI  - Communication challenges in complex medical environments.
AB  - The provision of health care is becoming increasingly complex and can involve
      multiple providers and care setting transitions, particularly as the population
      is living longer, and often with chronic disease. The Electronic Health Record
      (EHR) was intended to provide a comprehensive documentation of a patient's health
      related information; however, health care systems often function in isolation
      with EHRs that are unique only to that system. The EHR may also limit face-to
      face communication between treating physicians within the same system. It is only
      with diligent effort that changes in medical management plans are conveyed among
      providers. When multiple providers are involved in a patient's care, physician-to
      patient communication may also suffer, which can impact patient satisfaction and
      outcome. This article describes a scenario in which several lapses in
      communication occurred, and it outlines other common pitfalls while providing
      possible solutions for improving communication across the health care spectrum. 

PMID- 24893242
TI  - Liver transplant for intentional acetaminophen overdose and hepatic
      encephalopathy: a conflict between beneficence and justice.
AB  - In cases of severe acetaminophen-induced acute liver failure and hepatic
      encephalopathy, liver transplant can be the only real hope for neurologic
      recovery and indeed survival. In such cases, the bioethical principles of
      beneficence and justice often come into conflict. This article examines a case in
      which a neurologist managing an acetaminophen-overdose patient in the neurologic
      intensive care unit is faced with a conflict between her patient's need for a
      liver transplant and the needs of other patients on the transplant list. 

PMID- 24893244
TI  - Coding for patients with neurologic complications of systemic disease in the era
      of electronic health records.

PMID- 24893248
TI  - Patient management problem.

PMID- 24893251
TI  - Melanin-concentrating hormone in the medial preoptic area reduces active
      components of maternal behavior in rats.
AB  - Melanin-concentrating hormone (MCH) is an inhibitory neuropeptide mainly
      synthesized in neurons of the lateral hypothalamus and incerto-hypothalamic area
      of mammals that has been implicated in behavioral functions related to
      motivation. During lactation, this neuropeptide is also expressed in the medial
      preoptic area (mPOA), a key region of the maternal behavior circuitry. Notably,
      whereas MCH expression in the mPOA progressively increases during lactation,
      maternal behavior naturally declines, suggesting that elevated MCHergic activity
      in the mPOA inhibit maternal behavior in the late postpartum period. To explore
      this idea, we assessed the maternal behavior of early postpartum females
      following bilateral microinfusions of either MCH (50 and 100 ng/0.2 MUl/side) or
      the same volume of vehicle into the mPOA. As expected, females receiving 100 ng
      MCH into the mPOA exhibited significant deficits in the active components of
      maternal behavior, including retrieving and nest building. In contrast, nursing,
      as well as other behaviors, including locomotor activity, exploration, and
      anxiety-like behavior, were not affected by intra-mPOA MCH infusion. The present
      results, together with previous findings showing elevated expression of this
      neuropeptide toward the end of the postpartum period, suggest that modulation of
      mPOA function by MCH may contribute to the weaning of maternal responsiveness
      characteristic of the late postpartum period.

PMID- 24893252
TI  - Terahertz underdamped vibrational motion governs protein-ligand binding in
      solution.
AB  - Low-frequency collective vibrational modes in proteins have been proposed as
      being responsible for efficiently directing biochemical reactions and biological
      energy transport. However, evidence of the existence of delocalized vibrational
      modes is scarce and proof of their involvement in biological function absent.
      Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to
      study the depolarized Raman spectra of lysozyme and its complex with the
      inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational
      modes in the terahertz frequency domain are identified and shown to blue-shift
      and strengthen upon inhibitor binding. This demonstrates that the ligand-binding
      coordinate in proteins is underdamped and not simply solvent-controlled as
      previously assumed. The presence of such underdamped delocalized modes in
      proteins may have significant implications for the understanding of the
      efficiency of ligand binding and protein-molecule interactions, and has wider
      implications for biochemical reactivity and biological function. 

PMID- 24893253
TI  - Multi-transmit beam forming for fast cardiac imaging--experimental validation and
      in vivo application.
AB  - High frame rate (HFR) echocardiography may be of benefit for functional analysis
      of the heart. In current clinical equipment, HFR is obtained using multi-line
      acquisition (MLA) which typically requires broadening of transmit beams. As this
      may result in a significant degradation of spatial resolution and signal-to-noise
      ratio (SNR), the capacity of MLA to obtain high quality HFR images remains
      limited. As an alternative, we have demonstrated by computer simulation that
      simultaneously transmitting multiple focused beams into different directions
      [multi-line transmit (MLT)], can increase the frame rate without significantly
      compromising the spatial resolution or SNR. This study aimed to experimentally
      verify these theoretical predictions both in vitro and in vivo to demonstrate,
      for the first time, that cardiac MLT imaging is feasible. Hereto, the ultrasound
      advanced open platform, equipped with a 2.0 MHz phased array, was programmed to
      interleave MLT and conventional single line transmit (SLT) beam forming. Using
      these two beam forming methods, images of phantoms and healthy volunteers were
      acquired and investigated both qualitatively and quantitatively. The results
      confirmed our simulations that image quality of a 4MLT imaging system with a
      Tukey apodization scheme is very competitive to that of SLT while providing a 4
      times higher frame rate. It is also demonstrated that MLT can be combined with
      MLA to provide images at 12- to 16-fold frame rate (about 340-450 Hz) without
      significantly compromising spatial resolution and SNR. This is thus the first
      study to demonstrate that this new ultrasound imaging paradigm is viable which
      could have significant impact on future cardiac ultrasound systems. 

PMID- 24893255
TI  - A discriminative structural similarity measure and its application to video
      volume registration for endoscope three-dimensional motion tracking.
AB  - Endoscope 3-D motion tracking, which seeks to synchronize pre- and intra
      operative images in endoscopic interventions, is usually performed as video
      volume registration that optimizes the similarity between endoscopic video and
      pre-operative images. The tracking performance, in turn, depends significantly on
      whether a similarity measure can successfully characterize the difference between
      video sequences and volume rendering images driven by pre-operative images. The
      paper proposes a discriminative structural similarity measure, which uses the
      degradation of structural information and takes image correlation or structure,
      luminance, and contrast into consideration, to boost video-volume registration.
      By applying the proposed similarity measure to endoscope tracking, it was
      demonstrated to be more accurate and robust than several available similarity
      measures, e.g., local normalized cross correlation, normalized mutual
      information, modified mean square error, or normalized sum squared difference.
      Based on clinical data evaluation, the tracking error was reduced significantly
      from at least 14.6 mm to 4.5 mm. The processing time was accelerated more than 30
      frames per second using graphics processing unit. 

PMID- 24893254
TI  - Regional manifold learning for disease classification.
AB  - While manifold learning from images itself has become widely used in medical
      image analysis, the accuracy of existing implementations suffers from viewing
      each image as a single data point. To address this issue, we parcellate images
      into regions and then separately learn the manifold for each region. We use the
      regional manifolds as low-dimensional descriptors of high-dimensional
      morphological image features, which are then fed into a classifier to identify
      regions affected by disease. We produce a single ensemble decision for each scan
      by the weighted combination of these regional classification results. Each weight
      is determined by the regional accuracy of detecting the disease. When applied to
      cardiac magnetic resonance imaging of 50 normal controls and 50 patients with
      reconstructive surgery of Tetralogy of Fallot, our method achieves significantly
      better classification accuracy than approaches learning a single manifold across
      the entire image domain. 

PMID- 24893256
TI  - Extracting salient brain patterns for imaging-based classification of
      neurodegenerative diseases.
AB  - Neurodegenerative diseases comprise a wide variety of mental symptoms whose
      evolution is not directly related to the visual analysis made by radiologists,
      who can hardly quantify systematic differences. Moreover, automatic brain
      morphometric analyses, that do perform this quantification, contribute very
      little to the comprehension of the disease, i.e., many of these methods classify
      but they do not produce useful anatomo-functional correlations. This paper
      presents a new fully automatic image analysis method that reveals discriminative
      brain patterns associated to the presence of neurodegenerative diseases, mining
      systematic differences and therefore grading objectively any neurological
      disorder. This is accomplished by a fusion strategy that mixes together bottom-up
      and top-down information flows. Bottom-up information comes from a multiscale
      analysis of different image features, while the top-down stage includes learning
      and fusion strategies formulated as a max-margin multiple-kernel optimization
      problem. The capacity of finding discriminative anatomic patterns was evaluated
      using the Alzheimer's disease (AD) as the use case. The classification
      performance was assessed under different configurations of the proposed approach
      in two public brain magnetic resonance datasets (OASIS-MIRIAD) with patients
      diagnosed with AD, showing an improvement varying from 6.2% to 13% in the equal
      error rate measure, with respect to what has been reported by the feature-based
      morphometry strategy. In terms of the anatomical analysis, discriminant regions
      found by the proposed approach highly correlates to what has been reported in
      clinical studies of AD. 

PMID- 24893258
TI  - Prostate segmentation based on variant scale patch and local independent
      projection.
AB  - Accurate segmentation of the prostate in computed tomography (CT) images is
      important in image-guided radiotherapy; however, difficulties remain associated
      with this task. In this study, an automatic framework is designed for prostate
      segmentation in CT images. We propose a novel image feature extraction method,
      namely, variant scale patch, which can provide rich image information in a low
      dimensional feature space. We assume that the samples from different classes lie
      on different nonlinear submanifolds and design a new segmentation criterion
      called local independent projection (LIP). In our method, a dictionary containing
      training samples is constructed. To utilize the latest image information, we use
      an online updated strategy to construct this dictionary. In the proposed LIP,
      locality is emphasized rather than sparsity; local anchor embedding is performed
      to determine the dictionary coefficients. Several morphological operations are
      performed to improve the achieved results. The proposed method has been evaluated
      based on 330 3-D images of 24 patients. Results show that the proposed method is
      robust and effective in segmenting prostate in CT images. 

PMID- 24893259
TI  - A nonparametric temperature controller with nonlinear negative reaction for multi
      point rapid MR-guided HIFU ablation.
AB  - Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is a
      noninvasive method for thermal ablation, which exploits the capabilities of
      magnetic resonance imaging (MRI) for excellent visualization of the target and
      for near real-time thermometry. Oncological quality of ablation may be obtained
      by volumetric sonication under automatic feedback control of the temperature. For
      this purpose, a new nonparametric (i.e., model independent) temperature
      controller, using nonlinear negative reaction, was designed and evaluated for the
      iterated sonication of a prescribed pattern of foci. The main objective was to
      achieve the same thermal history at each sonication point during volumetric
      MRgHIFU. Differently sized linear and circular trajectories were investigated ex
      vivo and in vivo using a phased-array HIFU transducer. A clinical 3T MRI scanner
      was used and the temperature elevation was measured in five slices simultaneously
      with a voxel size of 1 *1 *5 mm(3) and temporal resolution of 4 s. In vivo
      results indicated a similar thermal history of each sonicated focus along the
      prescribed pattern, that was 17.3 +/- 0.5  degrees C as compared to 16  degrees C
      prescribed temperature elevation. The spatio-temporal control of the temperature
      also enabled meaningful comparison of various sonication patterns in terms of
      dosimetry and near-field safety. The thermal build-up tended to drift downwards
      in the HIFU transducer with a circular scan.

PMID- 24893257
TI  - Radial basis functions for combining shape and speckle tracking in 4D
      echocardiography.
AB  - Quantitative analysis of left ventricular deformation can provide valuable
      information about the extent of disease as well as the efficacy of treatment. In
      this work, we develop an adaptive multi-level compactly supported radial basis
      approach for deformation analysis in 3D+time echocardiography. Our method
      combines displacement information from shape tracking of myocardial boundaries
      (derived from B-mode data) with mid-wall displacements from radio-frequency-based
      ultrasound speckle tracking. We evaluate our methods on open-chest canines (N=8)
      and show that our combined approach is better correlated to magnetic resonance
      tagging-derived strains than either individual method. We also are able to
      identify regions of myocardial infarction (confirmed by postmortem analysis)
      using radial strain values obtained with our approach. 

PMID- 24893260
TI  - Multimodal registration and data fusion for cardiac resynchronization therapy
      optimization.
AB  - Cardiac resynchronization therapy (CRT) has been shown to improve cardiovascular
      function in specific patients suffering from heart failure. This procedure still
      needs to be optimized to overcome the high rate of implanted patients that do not
      respond to this therapy. We propose in this work a better characterization of the
      electro-mechanical (EM) coupling of each region of the left ventricle (LV) that
      could be useful to precise the best implantation site. A new descriptor is
      proposed with the extraction of local electro-mechanical delays. Their
      measurement is based on the fusion of anatomical, functional and electrical data
      acquired using computed tomography (CT), speckle tracking echocardiography (STE),
      and electro-anatomical mappings (EAM). We propose a workflow to place multimodal
      data in the same geometrical referential system and to extract local electro
      mechanical descriptors. It implies the fusion of electrical and mechanical data
      on a 3D+ t anatomical model of the LV. It mainly consists in four steps: 1) the
      modeling of the endocardium using a dynamic surface estimated from CT images; 2)
      the semi-interactive registration of EAM data and CT images; 3) the automatic
      registration of STE data on the dynamic model, using a metric based on Fourier
      descriptors and dynamic time warping; 4) the temporal alignment between EAM and
      STE and the estimation of local electro-mechanical delays. The proposed process
      has been applied to real data corresponding to five patients undergoing CRT.
      Results show that local electro-mechanical delays provide meaningful information
      on the local characterization of the LV and may be useful for the optimal pacing
      site selection in CRT. 

PMID- 24893261
TI  - Categorizing extent of tumor cell death response to cancer therapy using
      quantitative ultrasound spectroscopy and maximum mean discrepancy.
AB  - Quantitative ultrasound (QUS) spectroscopic techniques in conjunction with
      maximum mean discrepancy (MMD) have been proposed to detect, and to classify
      noninvasively the levels of cell death in response to cancer therapy
      administration in tumor models. Evaluation of xenograft tumor responses to cancer
      treatments were carried out using conventional-frequency ultrasound at different
      times after chemotherapy exposure. Ultrasound data were analyzed using
      spectroscopic techniques and multi-parametric QUS spectral maps were generated.
      MMD was applied as a distance criterion, measuring alterations in each tumor in
      response to chemotherapy, and the extent of cell death was classified into
      less/more than 20% and 40% categories. Statistically significant differences were
      observed between "pre-" and "post-treatment" groups at different times after
      chemotherapy exposure, suggesting a high capability of proposed framework for
      detecting tumor response noninvasively. Promising results were also obtained for
      categorizing the extent of cell death response in each tumor using the proposed
      framework, with gold standard histological quantification of cell death as ground
      truth. The best classification results were obtained using MMD when applied on
      histograms of QUS parametric maps. In this case, classification accuracies of
      84.7% and 88.2% were achieved for categorizing extent of tumor cell death into
      less/more than 20% and 40%, respectively. 

PMID- 24893262
TI  - Assessing acceptor substrate promiscuity of YjiC-mediated glycosylation toward
      flavonoids.
AB  - The acceptor substrate promiscuity of YjiC, a UDP-glycosyltransferase from
      Bacillus licheniformis, was explored with seven different classes (flavonols,
      flavanols, flavones, flavanones, chalcone, stilbene, and isoflavonoids) of 23
      flavonoid acceptors. For most of the polyphenols used in the reactions, the
      enzymatic bioconversion was significantly higher with the production of multiple
      glucosylated derivatives. This study highlights the highly flexible non
      regiospecific glycosylation ability of YjiC toward polyphenolic compounds. The
      catalytic potential of YjiC could be useful to generate a library of natural
      product glucosides. 

PMID- 24893263
TI  - Stereoselective C-glycosidation of D-fucose derivatives directed by the
      protective groups.
AB  - Stereoselectivity in the C-glycosidation of lactones derived from D-fucose by
      following Kishi's method, which involves the addition of a nucleophile onto a
      carbohydrate-derived lactone and subsequent reduction of the lactol, was found to
      be reliant on the nature of the C2 and C3 protective groups. Lactones bearing
      TBDMS protecting groups selectively afford 1,3-trans products (alpha anomer), in
      which the stereoselective outcome is in apparent concordance with Woerpel's
      model. On the other hand, their benzylated congeners produce the 1,3-cis products
      (beta anomer) as the major diastereoisomers. The latter results suggest an
      abnormal behavior during the stereoselective nucleophilic substitution at the
      anomeric position of the benzylated lactones.

PMID- 24893264
TI  - The discordance between planned use and actual receipt of immediate postpartum
      depot medroxyprogesterone among low-income women.
AB  - BACKGROUND: This study describes the patterns of planned use and actual receipt
      of immediate postpartum depot medroxyprogesterone (DMPA) prior to hospital
      discharge among low-income breastfeeding initiators. MATERIALS AND METHODS:
      Bivariate analyses among DMPA recipients by prenatal planned/unplanned use and
      the sensitivity of DMPA self-report relative to pharmacologic record were
      calculated. RESULTS: Among immediate postpartum DMPA recipients (n=58), 72.4%
      (n=42) did not plan to use DMPA. The sensitivity of self-reported DMPA use was
      89.7% (95% confidence interval, 85.2, 94.2). CONCLUSIONS: Clinically, it is
      unclear if the immediate postpartum period is the appropriate time to obtain
      consent and administer a long-acting contraceptive method. In our sample, women
      accurately recalled receiving DMPA in the immediate postpartum period. However,
      the majority did not plan to use this contraceptive method. Further high-quality
      qualitative and quantitative research regarding women's contraceptive plans and
      perception of the postpartum DMPA consent process and the healthcare provider's
      attitudes regarding consent and prescription of immediate postpartum DMPA are
      warranted.

PMID- 24893266
TI  - Universality and uniqueness in family medicine.

PMID- 24893267
TI  - Short report of a EURIPA survey on economics, austerity measures and health care
      (Hot Topic 5). EURIPA: the European Rural and Isolated Practitioners Association.

PMID- 24893265
TI  - The role of SUMO-1 in cardiac oxidative stress and hypertrophy.
AB  - AIMS: Small ubiquitin-like modifier type 1 (SUMO-1) has been shown to play a
      critical role in the dysfunction of the cardiac isoform of sarcoplasmic reticulum
      calcium ATPase (SERCA2a) pump in the setting of heart failure. In cardiac
      hypertrophy, the role of SUMO-1 has not been defined and our study's goals were
      to examine the effects of modulating SUMO-1 on the hypertrophic response both in
      vitro and in vivo and to examine whether oxidative stress (during cardiac
      hypertrophy) is abrogated by SUMO-1 gene transfer. RESULTS: In mice undergoing
      transverse aortic constriction (TAC), SUMO-1 levels increased slightly during the
      compensated stage of hypertrophy and then dropped sharply during the transition
      to heart failure. In isolated cardiomyocytes, SUMO-1 gene transfer inhibited the
      hypertrophic response in the presence of phenylephrine. Adeno-associated vector
      type 9 (AAV9) gene transfer of SUMO-1 prevented the heart from undergoing
      hypertrophy after TAC and prevented the development of left ventricular
      dysfunction. Furthermore, SUMO-1 gene transfer blocked the negative effects of
      H2O2 on SERCA2a activity in cardiac myocytes, while in vivo indices of oxidative
      stress were decreased by SUMO-1 in cardiac hypertrophy and heart failure.
      INNOVATION AND CONCLUSION: The results of this study indicate that post
      translational modifications of SERCA2a caused by the toxic environment of the
      hypertrophied and failing myocardium can be prevented by SUMO-1. Antioxid. Redox
      Signal. 21, 1986-2001.

PMID- 24893270
TI  - Enantioseparation of mandelic acid derivatives by high performance liquid
      chromatography with substituted beta-cyclodextrin as chiral mobile phase additive
      and evaluation of inclusion complex formation.
AB  - The enantioseparation of ten mandelic acid derivatives was performed by reverse
      phase high performance liquid chromatography with hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD) or sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) as chiral mobile
      phase additives, in which inclusion complex formations between cyclodextrins and
      enantiomers were evaluated. The effects of various factors such as the
      composition of mobile phase, concentration of cyclodextrins and column
      temperature on retention and enantioselectivity were studied. The peak
      resolutions and retention time of the enantiomers were strongly affected by the
      pH, the organic modifier and the type of beta-cyclodextrin in the mobile phase,
      while the concentration of buffer solution and temperature had a relatively low
      effect on resolutions. Enantioseparations were successfully achieved on a
      Shimpack CLC-ODS column (150*4.6mm i.d., 5MUm). The mobile phase was a mixture of
      acetonitrile and 0.10molL(-1) of phosphate buffer at pH 2.68 containing 20mmolL(
      1) of HP-beta-CD or SBE-beta-CD. Semi-preparative enantioseparation of about 10mg
      of alpha-cyclohexylmandelic acid and alpha-cyclopentylmandelic acid were
      established individually. Cyclodextrin-enantiomer complex stoichiometries as well
      as binding constants were investigated. Results showed that stoichiometries for
      all the inclusion complex of cyclodextrin-enantiomers were 1:1. 

PMID- 24893271
TI  - Comparison of two automated solid phase extractions for the detection of ten
      fentanyl analogs and metabolites in human urine using liquid chromatography
      tandem mass spectrometry.
AB  - Two types of automated solid phase extraction (SPE) were assessed for the
      determination of human exposure to fentanyls in urine. High sensitivity is
      required to detect these compounds following exposure because of the low dose
      required for therapeutic effect and the rapid clearance from the body for these
      compounds. To achieve this sensitivity, two acceptable methods for the detection
      of human exposure to seven fentanyl analogs and three metabolites were developed
      using either off-line 96-well plate SPE or on-line SPE. Each system offers
      different advantages: off-line 96-well plate SPE allows for high throughput
      analysis of many samples, which is needed for large sample numbers, while on-line
      SPE removes almost all analyst manipulation of the samples, minimizing the
      analyst time needed for sample preparation. Both sample preparations were coupled
      with reversed phase liquid chromatography and isotope dilution tandem mass
      spectrometry (LC-MS/MS) for analyte detection. For both methods, the resulting
      precision was within 15%, the accuracy within 25%, and the sensitivity was
      comparable with the limits of detection ranging from 0.002ng/mL to 0.041ng/mL.
      Additionally, matrix effects were substantially decreased from previous reports
      for both extraction protocols. The results of this comparison showed that both
      methods were acceptable for the detection of exposures to fentanyl analogs and
      metabolites in urine. 

PMID- 24893272
TI  - Water-soluble conjugated polymer as a platform for adenosine deaminase sensing
      based on fluorescence resonance energy transfer technique.
AB  - We report a new biosensor for adenosine deaminase (ADA) sensing based on water
      soluble conjugated poly(9,9-bis(6'-N,N,N-trimethylammonium)hexyl)fluorine
      phenylene (PFP) and fluorescence resonance energy transfer technique. In this
      biosensor, PFP, DNAc-FI labeled with fluorescein (FAM), and ethidium bromide (EB)
      were used as the fluorescence energy donor, resonance gate, and the final
      fluorescence energy acceptor, respectively. In the absence of ADA, the adenosine
      aptamer forms a hairpin-like conformation with adenosine, which is far from its
      complementary single-stranded DNA (DNAc-FI). When PFP is excited at 380 nm,
      fluorescein emits strong green fluorescence via one-step FRET while EB has no
      fluorescence. After addition of ADA, adenosine is hydrolyzed to inosine and then
      double-stranded DNA (dsDNA) is formed between the aptamer and DNAc-FI, followed
      by EB intercalating into dsDNA. Once PFP is excited, EB will emit strong yellow
      fluorescence after two-step FRET from PFP to fluorescein and from fluorescein to
      EB. The sensitive ADA detection then is realized with a low detection limit of
      0.5 U/L by measuring the FRET ratio of EB to fluorescein. Most importantly, the
      assay is accomplished homogeneously in 25 min without further treatments, which
      is much more simple and rapid than that reported in literature. Hence, this
      method demonstrates the sensitive, cost-effective, and rapid detection of ADA
      activity. It also opens an opportunity for designing promising sensors for other
      enzymes. 

PMID- 24893273
TI  - The progestin levonorgestrel disrupts gonadotropin expression and sex steroid
      levels in pubertal roach (Rutilus rutilus).
AB  - The aim of the present study was to investigate the effects of the synthetic
      progestin levonorgestrel (LNG) on the reproductive endocrine system of a teleost
      fish, the roach (Rutilus rutilus). Pubertal roach were exposed for 28 days in a
      flow-through system to four concentrations of LNG (3, 31, 312, and 3124 ng/l).
      Both males and females treated with 3124 ng/l LNG exhibited the upregulated
      levels of vitellogenin and oestrogen receptor 1 mRNA in the liver. At the same
      concentration, LNG caused a significant upregulation of the mRNA expression of
      the gene encoding luteinising hormone beta-subunit (lhbeta) and the suppression
      of the mRNA expression of the gene encoding follicle-stimulating hormone beta
      subunit (fshbeta) in the pituitary of both male and female roach. A lower LNG
      concentration (312 ng/l) suppressed mRNA expression of fshbeta in males only.
      Females treated with 3124 ng/l LNG exhibited significantly lower plasma 11
      ketotestosterone (11-KT) and oestradiol (E2) concentrations, whereas their
      testosterone (T) level was higher compared with the control. Females exposed to
      312 ng/l LNG presented significantly lower plasma E2 concentrations. Males
      exposed to >=31 ng/l LNG exhibited significantly reduced 11-KT levels. As
      determined through a histological analysis, the ovaries of females were not
      affected by LNG exposure, whereas the testes of males exposed to 31 and 312 ng/l
      LNG exhibited a significantly higher percentage of spermatogonia B compared with
      the control. The results of the present study demonstrate that LNG disrupts the
      reproductive system of pubertal roach by affecting the pituitary gonadotropin
      expression and the sex steroid levels. This disruption was determined to occur in
      males after exposure to an environmentally relevant concentration (31 ng/l).
      Moreover, the highest tested concentration of LNG (3124 ng/l) exerted an
      oestrogenic effect on fish of both sexes.

PMID- 24893274
TI  - Identifying core foods for total diet studies: a comparison of four different
      approaches.
AB  - Total diet studies (TDS) are recognised as a cost-effective approach in
      estimating dietary exposure to chemicals in food. It has been advised that
      candidate foods for inclusion in TDS analysis should represent a large part of
      the typical diet to estimate accurately the exposure of a population group. To
      date a variety of approaches have been used to determine which foods should be
      included in a core TDS food list, with no agreed method. Therefore, the aim of
      this study was to compare four of these approaches by creating TDS food lists for
      adult populations in Europe using summary statistics data from the EFSA
      Comprehensive Food Consumption Database. Both a food group approach and a total
      diet approach were employed, and foods were selected for inclusion in the TDS
      food lists if they met the criteria as defined by consumption weight and/or a 5%
      consumer rate. Using all four approaches the representation of the diet across
      the TDS food lists was > 85%. The food group approach showed a slight advantage
      in diet representation, but produced considerably longer TDS food lists in
      comparison with the total diet approach. The addition of a 5% consumer rate to
      both approaches had little impact on results. In conclusion, the total diet
      approach may act as a more cost-effective approach in comparison with the food
      group approach while still achieving comprehensive results in the creation of
      core TDS food lists. 

PMID- 24893275
TI  - Clinical relevance of pharmacological and physiological data in intrathecal
      baclofen therapy.
AB  - OBJECTIVE: To review all pharmacological and physiological data available on
      intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice
      and future research. DATA SOURCES: PubMed was searched for relevant anatomic,
      physiological, and pharmacological data available on ITB. STUDY SELECTION: All
      currently available data on ITB pharmacokinetics (PKs) and pharmacodynamics (PDs)
      in both human and animal studies were reviewed and combined with the anatomy and
      physiology of the intrathecal space and cerebrospinal fluid flow. DATA
      EXTRACTION: Only 4 studies reported PK data on ITB in humans. More studies
      reported PD data on ITB; however, none were combined with PK data. More detailed
      data on PK could be gathered from studies using an animal model. DATA SYNTHESIS:
      ITB does not spread equally over the intrathecal space after injection, but it
      diffuses according to a concentration gradient. ITB distribution can be
      influenced by the location of the catheter tip and by changing the infusion mode.
      CONCLUSIONS: The pharmacological and physiological data on ITB can be used to
      support decisions in clinical practice concerning drug concentration, infusion
      regimens, localization of the catheter tip, and management of tolerance; however,
      some strategies have little evidence in humans.

PMID- 24893276
TI  - New directions for the study of incarcerated older adults: using social capital
      theory.
AB  - As the population of older adults continues to rise, so, too, does the population
      of older adults in prison. The body of literature on older adults in corrections
      is scant, particularly with regard to health and social functioning. Past studies
      of aging inmates primarily focus on health care and related costs. The purpose of
      this article is twofold: (a) outline and synthesize the research on older adults
      living in prison; and (b) propose a framework for future research and
      intervention development based on social capital theory. Recommendations for
      social work practice, programs, and research are discussed.

PMID- 24893277
TI  - Solution-processed barium salts as charge injection layers for high performance N
      channel organic field-effect transistors.
AB  - N-channel organic field-effect transistors (OFETs) have generally shown lower
      field-effect mobilities (MUFET) than their p-type counterparts. One of the
      reasons is the energetic misalignment between the work function (WF) of commonly
      used charge injection electrode, i.e. gold (Au), and the lowest unoccupied
      molecular orbital (LUMO) of n-channel electron-transporting organic
      semiconductors. Here, we report barium salts as solution-processed interlayers,
      to improve the electron-injection and/or hole-blocking in top-gate/bottom-contact
      n-channel OFETs, based on poly{[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8
      bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-dithiophene)} (P(NDI2OD-T2)) and
      phenyl-C61-butyric acid methyl ester (PC61BM). Two different barium salts, barium
      hydroxide (Ba(OH)2) and barium chloride (Ba(Cl)2), are employed as the ultrathin
      interlayer (~2 nm); and they effectively tune the WF of Au from 4.9 eV, to as low
      as 3.5 eV. The resulting n-channel OFETs exhibit significantly improved MUFET,
      approaching 2.6 cm(2)/(V s) and 0.1 cm(2)/(V s) for the best P(NDI2OD-T2) and
      PC61BM devices, respectively, with Ba(OH)2 as interlayer. 

PMID- 24893278
TI  - Career lasting influences.

PMID- 24893279
TI  - Letter from the editor.

PMID- 24893280
TI  - Clinical biomarkers in colorectal cancer.
AB  - Colorectal cancer remains the second leading cause of cancer-related death in the
      United States. While chemo- therapy remains the backbone upon which treatment for
      meta- static colorectal cancer is built, targeted therapies have been employed,
      albeit with mixed results, in the management of this disease. Nonetheless,
      increased understanding in recent years of the complexity and heterogeneity of
      cellular abnormalities driving these tumors has identified potential targets for
      future interven- tions. This article will review the seminal biomarkers of predic
      tive and prognostic importance currently used in the treatment of patients with
      colorectal cancer, and will highlight additional promising biomarkers which may
      be incorporated into clinical practice in the future. 

PMID- 24893281
TI  - The potential role for neoadjuvant therapy in renal cell carcinoma.
AB  - Surgical resection remains the standard of care for clini- cally localized renal
      cell carcinoma (RCC). Nearly 1 in 4 patients will have a recurrence after surgery
      performed with curative intent, and stand to benefit from additional therapy.
      Currently, no proven adjuvant or neoadjuvant therapies are available. A number of
      phase 3 adjuvant therapy trials are ongoing that are evaluating small-molecule
      drugs approved for metastatic RCC. The outcomes of these trials may provide
      insights for designing future phase 3 neoadjuvant therapy trials. Several phase 2
      neoadjuvant trials for RCC have recently been completed or are ongoing. These
      trials have established the safety and response rates associated with several
      agents, and will pave the way for future phase 3 trials of neoadjuvant therapy
      for RCC. Neoadjuvant therapies may be useful for decreasing the risk of
      recurrence after surgery, maximiz- ing nephron sparing, and evaluating molecular
      effects of targeted therapies in human tumors. 

PMID- 24893282
TI  - New antiplatelet agents: are we better off now than we were with aspirin?

PMID- 24893284
TI  - Management of the axilla in breast cancer patients undergoing neoadjuvant
      therapy.

PMID- 24893283
TI  - Watching and waiting in mantle cell lymphoma.

PMID- 24893285
TI  - Neoadjuvant pertuzumab in early HER2-positive breast cancer.

PMID- 24893286
TI  - Radium-223: the newest option in metastatic castration-resistant prostate cancer.

PMID- 24893287
TI  - Metastatic pancreatic poorly differentiated neuroendocrine carcinoma: current
      treatment considerations.

PMID- 24893288
TI  - Evolving understanding and management of poorly differentiated neuroendocrine
      tumors.

PMID- 24893289
TI  - Molecular organization of the 25S-18S rDNA IGS of Fagus sylvatica and Quercus
      suber: a comparative analysis.
AB  - The 35S ribosomal DNA (rDNA) units, repeated in tandem at one or more chromosomal
      loci, are separated by an intergenic spacer (IGS) containing functional elements
      involved in the regulation of transcription of downstream rRNA genes. In the
      present work, we have compared the IGS molecular organizations in two divergent
      species of Fagaceae, Fagus sylvatica and Quercus suber, aiming to comprehend the
      evolution of the IGS sequences within the family. Self- and cross-hybridization
      FISH was done on representative species of the Fagaceae. The IGS length
      variability and the methylation level of 18 and 25S rRNA genes were assessed in
      representatives of three genera of this family: Fagus, Quercus and Castanea. The
      intergenic spacers in Beech and Cork Oak showed similar overall organizations
      comprising putative functional elements needed for rRNA gene activity and
      containing a non-transcribed spacer (NTS), a promoter region, and a 5'-external
      transcribed spacer. In the NTS: the sub-repeats structure in Beech is more
      organized than in Cork Oak, sharing some short motifs which results in the lowest
      sequence similarity of the entire IGS; the AT-rich region differed in both
      spacers by a GC-rich block inserted in Cork Oak. The 5'-ETS is the region with
      the higher similarity, having nonetheless different lengths. FISH with the NTS-5'
      ETS revealed fainter signals in cross-hybridization in agreement with the
      divergence between genera. The diversity of IGS lengths revealed variants from ~
      2 kb in Fagus, and Quercus up to 5.3 kb in Castanea, and a lack of correlation
      between the number of variants and the number of rDNA loci in several species.
      Methylation of 25S Bam HI site was confirmed in all species and detected for the
      first time in the 18S of Q. suber and Q. faginea. These results provide important
      clues for the evolutionary trends of the rDNA 25S-18S IGS in the Fagaceae family.

PMID- 24893291
TI  - Timed deletion of Twist1 in the limb bud reveals age-specific impacts on autopod
      and zeugopod patterning.
AB  - Twist1 encodes a transcription factor that plays a vital role in limb
      development. We have used a tamoxifen-inducible Cre transgene, Ubc-CreERT2, to
      generate time-specific deletions of Twist1 by inducing Cre activity in mouse
      embryos at different ages from embryonic (E) day 9.5 onwards. A novel forelimb
      phenotype of supernumerary pre-axial digits and enlargement or partial
      duplication of the distal radius was observed when Cre activity was induced at
      E9.5. Gene expression analysis revealed significant upregulation of Hoxd10,
      Hoxd11 and Grem1 in the anterior half of the forelimb bud at E11.5. There is also
      localized upregulation of Ptch1, Hand2 and Hoxd13 at the site of ectopic digit
      formation, indicating a posterior molecular identity for the supernumerary
      digits. The specific skeletal phenotypes, which include duplication of digits and
      distal zeugopods but no overt posteriorization, differ from those of other Twist1
      conditional knockout mutants. This outcome may be attributed to the deferment of
      Twist1 ablation to a later time frame of limb morphogenesis, which leads to the
      ectopic activation of posterior genes in the anterior tissues after the
      establishment of anterior-posterior anatomical identities in the forelimb bud. 

PMID- 24893292
TI  - Enhancement characteristics and impact on image quality of two gadolinium
      chelates at equimolar doses for time-resolved 3-Tesla MR-angiography of the calf
      station.
AB  - PURPOSE: To compare enhancement characteristics and image quality of two
      macrocyclic gadolinium chelates, gadoterate meglumine and gadobutrol, in low
      dose, time-resolved MRA of the calf station. MATERIALS AND METHODS: 100
      consecutive patients with peripheral arterial disease (stages II-IV) were
      retrospectively analysed. Fifty patients were included in each group - 32 men and
      18 women for gadobutrol (mean age 67 years) and 34 men, 16 women for gadoterate
      meglumine (mean age 64 years). 0.03 mmol/kg bw of either gadobutrol or gadoterate
      meglumine was injected. Gadobutrol was diluted 1 ? 1 with normal saline (0.9%
      NaCl) to provide similar injection volume and bolus geometry compared to the
      undiluted 0.5 M dose of gadoterate meglumine. Signal-to-noise-ratio (SNR),
      contrast-to-noise-ratio (CNR) and image quality were analysed and compared
      between the two groups. RESULTS: Mean SNR ranged from 83.0 +/- 46.7 (peroneal
      artery) to 96.4 +/- 64.5 (anterior tibial artery) for gadobutrol, and from 37.6
      +/- 13.8 (peroneal artery) to 45.3 +/- 16.4 (anterior tibial artery) for the
      gadoterate meglumine group (p<0.0001). CNR values ranged from 30.1 +/- 20.1
      (peroneal artery) to 37.6 +/- 26.0 (anterior tibial artery) for gadobutrol and
      from 14.9 +/- 8.0 (peroneal artery) to 18.6 +/- 16.4 (anterior tibial artery) for
      gadoterate meglumine (p<0.0001). No significant difference in image quality was
      found except for the peroneal arteries (p = 0.006 and p = 0.04). Interreader
      agreement was excellent (kappa 0.87-0.93). CONCLUSION: The significantly better
      enhancement as assessed by SNR and CNR provided by gadobutrol compared to
      gadoterate meglumine does not translate into substantial differences in image
      quality in an equimolar, low-dose, time-resolved MRA protocol of the calves.

PMID- 24893290
TI  - Smoking cessation and the risk of diabetes mellitus and impaired fasting glucose:
      three-year outcomes after a quit attempt.
AB  - Weight gain after smoking cessation may increase diabetes mellitus and impaired
      fasting glucose (IFG) risk. This study evaluated associations between smoking
      cessation and continued smoking with incident diabetes and IFG three years after
      a quit attempt. The 1504 smokers (58% female) were mean (standard deviation) 44.7
      (11.1) years old and smoked 21.4 (8.9) cigarettes/day. Of 914 participants with
      year 3 data, the 238 abstainers had greater weight gain, increase in waist
      circumference, and increase in fasting glucose levels than the 676 continuing
      smokers (p <= 0.008). In univariate analyses, Year 3 abstinence was associated
      with incident diabetes (OR = 2.60, 95% CI 1.44-4.67, p = .002; 4.3% absolute
      excess) and IFG (OR = 2.43, 95% CI 1.74-3.41, p<0.0001; 15.6% absolute excess).
      In multivariate analyses, incident diabetes was associated independently with
      older age (p = 0.0002), higher baseline body weight (p = 0.021), weight gain (p =
      0.023), baseline smoking rate (p = 0.008), baseline IFG (p<0.0001), and baseline
      hemoglobin A1C (all p<0.0001). Smoking more at baseline predicted incident
      diabetes among eventual abstainers (p<0.0001); weighing more at baseline
      predicted incident diabetes among continuing smokers (p = 0.0004). Quitting
      smoking is associated with increased diabetes and IFG risk. Independent risk
      factors include older age, baseline body weight, baseline glycemic status, and
      heavier pre-quit smoking. These findings may help target smokers for
      interventions to prevent dysglycemia. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00332644.

PMID- 24893293
TI  - Chronic alcohol consumption leads to neurochemical changes in the nucleus
      accumbens that are not fully reversed by withdrawal.
AB  - Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus
      accumbens (NAc) seem to play a major role in the rewarding effects of alcohol.
      This study investigated the relationship between chronic alcohol consumption and
      subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and
      the possible involvement of nerve growth factor (NGF) in mediating the effects of
      ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats
      subsequently deprived from ethanol during 2months were used to estimate the total
      number and the somatic volume of NPY and cholinergic interneurons, and the
      numerical density of cholinergic varicosities in the NAc. The tissue content of
      choline acetyltransferase (ChAT) and catecholamines were also determined. The
      number of NPY interneurons increased during alcohol ingestion and returned to
      control values after withdrawal. Conversely, the number and the size of
      cholinergic interneurons, and the amount of ChAT were unchanged in ethanol
      treated and withdrawn rats, but the density of cholinergic varicosities was
      reduced by 50% during alcohol consumption and by 64% after withdrawal. The
      concentrations of dopamine and norepinephrine were unchanged both during alcohol
      consumption and after withdrawal. The administration of NGF to withdrawn rats
      significantly increased the number of NPY-immunoreactive neurons, the size of
      cholinergic neurons and the density of cholinergic varicosities. Present data
      show that chronic alcohol consumption leads to long-lasting neuroadaptive changes
      of the cholinergic innervation of the NAc and suggest that the cholinergic system
      is a potential target for the development of therapeutic strategies in alcoholism
      and abstinence. 

PMID- 24893294
TI  - Subchronic atrazine exposure changes defensive behaviour profile and disrupts
      brain acetylcholinesterase activity of zebrafish.
AB  - Animal behaviour is the interaction between environment and an individual
      organism, which also can be influenced by its neighbours. Variations in
      environmental conditions, as those caused by contaminants, may lead to
      neurochemical impairments altering the pattern of the behavioural repertoire of
      the species. Atrazine (ATZ) is an herbicide widely used in agriculture that is
      frequently detected in surface water, affecting non-target species. The zebrafish
      is a valuable model organism to assess behavioural and neurochemical effects of
      different contaminants since it presents a robust behavioural repertoire and also
      all major neurotransmitter systems described for mammalian species. The goal of
      this study was to evaluate the effects of subchronic ATZ exposure in defensive
      behaviours of zebrafish (shoaling, thigmotaxis, and depth preference) using the
      split depth tank. Furthermore, to investigate a putative role of cholinergic
      signalling on ATZ-mediated effects, we tested whether this herbicide alters
      acetylcholinesterase (AChE) activity in brain and muscle preparations. Fish were
      exposed to ATZ for 14days and the following groups were tested: control (0.2%
      acetone) and ATZ (10 and 1000MUg/L). The behaviour of four animals in the same
      tank was recorded for 6min and biological samples were prepared. Our results
      showed that 1000MUg/L ATZ significantly increased the inter-fish distance, as
      well as the nearest and farthest neighbour distances. This group also presented
      an increase in the shoal area with decreased social interaction. No significant
      differences were detected for the number of animals in the shallow area, latency
      to enter the shallow and time spent in shallow and deep areas of the apparatus,
      but the ATZ 1000 group spent significantly more time near the walls. Although ATZ
      did not affect muscular AChE, it significantly reduced AChE activity in brain.
      Exposure to 10MUg/L ATZ did not affect behaviour or AChE activity. These data
      suggest that ATZ impairs defensive behaviours of zebrafish, which could be
      related to its action on brain cholinergic neurotransmission. Moreover, the use
      of the split depth tank could be an alternative strategy to assess group
      behaviour and depth preference after exposure to chemical compounds. 

PMID- 24893296
TI  - The Cali Cancer Registry an example for Latin America.

PMID- 24893295
TI  - Physiological and proteomic analyses of Saccharum spp. grown under salt stress.
AB  - Sugarcane (Saccharum spp.) is the world most productive sugar producing crop,
      making an understanding of its stress physiology key to increasing both sugar and
      ethanol production. To understand the behavior and salt tolerance mechanisms of
      sugarcane, two cultivars commonly used in Brazilian agriculture, RB867515 and
      RB855536, were submitted to salt stress for 48 days. Physiological parameters
      including net photosynthesis, water potential, dry root and shoot mass and
      malondialdehyde (MDA) content of leaves were determined. Control plants of the
      two cultivars showed similar values for most traits apart from higher root dry
      mass in RB867515. Both cultivars behaved similarly during salt stress, except for
      MDA levels for which there was a delay in the response for cultivar RB867515.
      Analysis of leaf macro- and micronutrients concentrations was performed and the
      concentration of Mn(2+) increased on day 48 for both cultivars. In parallel, to
      observe the effects of salt stress on protein levels in leaves of the RB867515
      cultivar, two-dimensional gel electrophoresis followed by MS analysis was
      performed. Four proteins were differentially expressed between control and salt
      treated plants. Fructose 1,6-bisphosphate aldolase was down-regulated, a germin
      like protein and glyceraldehyde 3-phosphate dehydrogenase showed increased
      expression levels under salt stress, and heat-shock protein 70 was expressed only
      in salt-treated plants. These proteins are involved in energy metabolism and
      defense-related responses and we suggest that they may be involved in protection
      mechanisms against salt stress in sugarcane.

PMID- 24893297
TI  - Trends of cancer incidence and mortality in Cali, Colombia. 50 years experience.
AB  - PURPOSE: The Population-based Cancer Registry of Cali aims to report all new
      cases in permanent residents within the limits of the city of Cali. Time trends
      of cancer incidence and mortality are described. The registry has been in
      continuous operation for 50 years. METHODS: CANCER CASES REPORTS ARE OBTAINED
      ACTIVELY BY VISITING ALL SOURCES OF INFORMATION: hospitals, pathology
      departments, hematology laboratories, radiotherapy centers, government offices
      where death certificates are processed and physician's offices. It is estimated
      that the reporting is at least 95% complete. RESULTS: Drastic decreases are
      documented in rates for tumors causally related to infectious agents, especially
      cancers of the uterine cervix and the stomach. Gradual increases are documented
      in rates of tumors linked to affluence and the metabolic syndrome, especially
      cancers of the colon and the female breast. An unexpected increase in the
      incidence of papillary carcinoma of the thyroid gland in women is reported.
      Tobacco-related cancers, especially cancer of the lung, showed marked increase in
      incidence rates around 1970, apparently the beginning of an epidemic similar to
      the one reported in Western societies. But the increase in incidence stopped
      around 1980, resulting from a strong anti-smoking campaign launched in Colombia
      in the 1970s. CONCLUSIONS: The findings have influenced prevention strategies
      implemented by public health authorities, specially the establishment of a city
      wide program to prevent cervix cancer via widespread use of vaginal cytology and
      anti-smoking campaigns. Also, new population-based cancer registries have been
      established in other Colombian cities as well as in Ecuador.

PMID- 24893298
TI  - Cancer incidence and mortality in the municipality of Pasto, 1998 - 2007.
AB  - INTRODUCTION: In Colombia, information on cancer morbidity at the population
      level is limited. Incidence estimates for most regions are based on mortality
      data. To improve the validity of these estimates, it is necessary that other
      population-based cancer registries, as well as Cali, provide cancer risk
      information. OBJECTIVE: To describe the incidence and cancer mortality in the
      municipality of Pasto within the 1998-2007 period. METHODS: The study population
      belongs to rural and urban areas of the municipality of Pasto. Collection,
      processing, and systematization of the data were performed according to
      internationally standardized parameters for population-based cancer registries.
      The cancer incidence and mortality rates were calculated by gender, age, and
      tumor. RESULTS: During the 1998-2007 period 4,986 new cases of cancer were
      recorded of which 57.7% were in female. 2,503 deaths were presented, 52% in
      female. Neoplasm-associated infections are the leading cause of cancer morbidity
      in Pasto: stomach cancer in males and cervical cancer in females. DISCUSSION:
      Cancer in general is a major health problem for the population of the
      municipality of Pasto. The overall behavior of the increasing incidence and
      cancer mortality in relation to other causes of death show the need to implement
      and strengthen prevention and promotion programs, focusing especially on tumors
      that produce greater morbidity and mortality in the population.

PMID- 24893299
TI  - Follow-up of the tumor load in patients with de novo chronic myeloid leukemia and
      in complete cytogenetic remission treated with imatinib in Colombia.
AB  - OBJECTIVE: To evaluate the hematological, cytogenetic, and molecular responses in
      Colombian patients with CML chronic myeloid leukemia (CML) treated with imatinib.
      METHODS: Two groups of patients, one with the novo diagnostic and another in
      state of complete cytogenetic remission were followed for 12 months with
      quantitative PCR evaluations every three months and with chromosomal analysis
      every 6 months. RESULTS: The group with the novo diagnosis showed 50% of complete
      cytogenetic remission at 12 months while the other 50% were considered to have
      primary resistance. Respect the molecular analysis, 10.5% of the patients reached
      undetectable BCR-ABL transcripts at 12 months. In the complete cytogenetic
      remission group, 10.6% lost the state of complete cytogenetic remission at 12
      months, 50% reached undetectable BCR-ABL transcripts but 10% showed levels higher
      than 10%, which in our standardization was equal to no molecular response.
      CONCLUSIONS: Despite having received the conventional dosages of 400 mg/day of
      imatinib, the cytogenetic and molecular responses obtained in our group of
      Colombian patients with CML, were lower than those in other international
      studies.

PMID- 24893301
TI  - Cancer incidence and mortality in Manizales 2003-2007.
AB  - OBJECTIVE: To describe cancer incidence and mortality in Manizales during the
      2003-2007 period from population-based information. METHODS: The information was
      obtained from the Manizales Cancer Registry and DANE. We analyzed new cases and
      cancer deaths of individuals residing in Manizales from 1 January 2003 to 31
      December 2007. Cases reported correspond to primary invasive malignant tumors, in
      all locations, except basal cell carcinoma of the skin. We checked the internal
      consistency of the data and applied quality indicators suggested by the IARC. The
      population at risk was obtained from population projections (1985 -- 2020, DANE).
      Specific rates were estimated by gender and age (18 quinquennial groups), and
      standardized to the world population directly referenced. RESULTS: There were
      3416 new cases and 1895 deaths from cancer. The age- standardized incidence rate
      (ASR) per 100,000 people-years for all primary locations (except skin) was 162.4
      in women and 166.2 in men. Cancer accounted for 19.8% of mortality in Manizales
      with ASR per 100,000 people-years of 92.1 in men and 83.6 in women. CONCLUSIONS:
      The risk of developing cancer or dying from cancer in Manizales is intermediate
      and similar to national estimates. The information generated by the PCR-M meets
      international quality standards, so it is necessary to ensure sustainability and
      improvement.

PMID- 24893300
TI  - Epidemiological surveillance of the HIV/AIDS complex through the analysis of
      trends in the incidence of Kaposi's sarcoma in Cali, Colombia.
AB  - INTRODUCTION: The Kaposi's sarcoma (KS) incidence has markedly changed in the
      general population since the onset of the AIDS epidemic in the eighties and after
      the introduction of the Highly Active Antiretroviral Therapy (HAART) in the
      nineties. OBJECTIVE: To investigate incidence rate trends for Kaposi's sarcoma
      before and during the (HIV/AIDS) epidemic in Cali, Colombia. METHODS: Exploratory
      ecological study that included all Kaposi's sarcoma cases identified by the Cali
      Cancer Registry from 1962-2007, and 12,887 cases of HIV/AIDS recorded in the
      Municipal Health Secretariat of Cali between 1986 and 2010. The joinpoint
      regression model was used to conduct the incidence rate analyses between the
      years 1962 and 2010. RESULTS: A total of 349 KS cases were identified during the
      study period. Only 5.3% of the cases (n=20) were diagnosed in the pre-epidemic
      era (1963-1987), of these, 35% were women, and 90% of the tumors were located on
      the skin. In contrast, 94.7% of KS cases (n=329) were discovered after the
      emergence of HIV-AIDS. There was a significant decrease in the proportion of
      women (10.9%, p <0.001) and an increase in the frequency of tumors with an extra
      cutaneous location (19.1%, p <0.01) compared to those cases diagnosed in the pre
      epidemic era. Notification rates of HIV/AIDS have decreased since 2002 in both
      genders but KS incidence rates have decreased since 2004 in men only. CONCLUSION:
      The downward trend in the incidence of these diseases may be associated with
      factors that prevent the transmission of HIV infection or limit the spread of HIV
      in the community. Cancer registries represent a resource for timely, population
      based surveil-lance of HIV-associated malignancies in Cali, Colombia.

PMID- 24893302
TI  - Cancer incidence and mortality in the Bucaramanga metropolitan area, 2003-2007.
AB  - INTRODUCTION: Cancer is an important cause of morbidity and mortality worldwide.
      Population-based cancer registries (PBCRs) make possible to estimate the burden
      of this condition. AIM: To estimate cancer incidence and mortality rates in the
      Bucaramanga Metropolitan Area (BMA) during 2003-2007. METHODS: Incident cases of
      invasive cancer diagnosed during 2003-2007 were identified from the Bucaramanga
      Metropolitan Area PBCR (BMA-PBCR). Population counts and mortality were obtained
      from the Colombian National Administrative Department of Statistics (NADS). We
      estimated total and cancer-specific crude incidence and mortality rates by age
      group and sex, as well as age-standardized (Segi's world population) incidence
      (ASIR(W)) and mortality (ASMR(W)) rates. Statistical analyses were conducted
      using CanReg4 and Stata/IC 10.1. RESULTS: We identified 8,225 new cases of cancer
      excluding non-melanoma skin cancer (54.3% among women). Of all cases, 6,943
      (84.4%) were verified by microscopy and 669 (8.1%) were detected only by death
      certificate. ASIR(W) for all invasive cancers was 162.8 per 100,000 women and
      177.6 per 100,000 men. Breast, cervix, colorectal, stomach and thyroid were the
      most common types of cancer in women. In men, the corresponding malignancies were
      prostate, stomach, colorectal, lung and lymphoma. ASMR(W) was 84.5 per 100,000
      person-years in women and 106.2 per 100,000 person-years in men. Breast and
      stomach cancer ranked first as causes of death in those groups, respectively.
      CONCLUSION: Overall, mortality rates in our region are higher than national
      estimates possibly due to limited effectiveness of secondary prevention
      strategies. Our work emphasizes the importance of maintaining high-quality,
      nationwide PBCRs.

PMID- 24893303
TI  - Epidemiology of cervical cancer in Colombia.
AB  - Worldwide, cervical cancer is the third most common cancer in women, and the
      first or second most common in developing countries. Cervical cancer remains in
      Colombia the first cause of cancer mortality and the second cause of cancer
      incidence among women, despite the existence of screening programs during the
      last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per
      100,000and Pasto 27 per 100,000. The Cali cancer registry has reported a
      progressive decrease in the age standardized incidence and mortality rates of
      cervical cancer over the past 40 years. Reasons for the decline in incidence and
      mortality of cervical cancer are multiple and probably include: improvement in
      socio-economic conditions, decrease in parity rates and some effect of screening
      programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural
      history studies have now revealed that HPVs are the commonest of the sexually
      transmitted infections in most populations. Most HPV exposures result in
      spontaneous clearance without clinical manifestations and only a small fraction
      of the infected persons, known as chronic or persistent carriers, will retain the
      virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of
      cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and
      35) account for about 90% of cervical cancer. Case-control studies also allowed
      the identification of the following cofactors that acting together with HPV
      increase the risk of progression from HPV persistent infection to cervical
      cancer: tobacco, high parity, long term use of oral contraceptives and past
      infections with herpes simplex type 2 and Chlamydia trachomatis. The
      demonstration that infection with certain types of human papillomavirus (HPV) is
      not only the main cause but also a necessary cause of cervical cancer has led to
      great advances in the prevention of this disease on two fronts: (i) Primary
      prevention by the use of prophylactic HPV vaccines; and (ii) secondary prevention
      by increasing the accuracy of cervical cancer screening. 

PMID- 24893305
TI  - The tobacco gardens.

PMID- 24893304
TI  - Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative
      individuals, improved with anti-human herpes virus treatment.
AB  - Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial,
      fungal, parasite and viral infections. They can also be found in autoimmune and
      neoplastic diseases, common variable immunodeficiency syndrome, physical,
      psychological and traumatic stress, malnutrition and immunosuppressive therapy.
      Besides, they can also be brought into relation, without a known cause, with
      idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus,
      specially the human immunodeficiency virus, is the most frequently cause.
      However, many acute viral infections, including cytomegalovirus and Epstein Barr
      virus can be associated with transient lymphocytopenia and CD4+ T
      lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T
      lymphocytopenia are temporary and overcome when the disease improves.
      Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by
      human herpes virus has not been reported. We describe 6 cases of human
      immunodeficiency virus negative patients, with chronic cytomegalovirus and
      Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms
      of cellular immunodeficiency. These patients improved rapidly with ganciclovir or
      valganciclovir treatment. We claim here that it is important to consider the
      chronic human herpes virus infection in the differential diagnosis of profoundly
      CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in
      order to start effective treatment and to determine, in future studies, the
      impact of chronic human herpes virus infection in human beings' health. 

PMID- 24893306
TI  - Innate pattern recognition and categorization in a jumping spider.
AB  - The East African jumping spider Evarcha culicivora feeds indirectly on vertebrate
      blood by preferentially preying upon blood-fed Anopheles mosquitoes, the vectors
      of human malaria1, using the distinct resting posture and engorged abdomen
      characteristic of these specific prey as key elements for their recognition. To
      understand perceptual categorization of objects by these spiders, we investigated
      their predatory behavior toward different digital stimuli--abstract 'stick
      figure' representations of Anopheles constructed solely by known key
      identification elements, disarranged versions of these, as well as non-prey items
      and detailed images of alternative prey. We hypothesized that the abstract images
      representing Anopheles would be perceived as potential prey, and would be
      preferred to those of non-preferred prey. Spiders perceived the abstract stick
      figures of Anopheles specifically as their preferred prey, attacking them
      significantly more often than non-preferred prey, even when the comprising
      elements of the Anopheles stick figures were disarranged and disconnected from
      each other. However, if the relative angles between the elements of the
      disconnected stick figures of Anopheles were altered, the otherwise identical set
      of elements was no longer perceived as prey. These data show that E. culicivora
      is capable of making discriminations based on abstract concepts, such as the
      hypothetical angle formed by discontinuous elements. It is this inter-element
      angle rather than resting posture that is important for correct identification of
      Anopheles. Our results provide a glimpse of the underlying processes of object
      recognition in animals with minute brains, and suggest that these spiders use a
      local processing approach for object recognition, rather than a holistic or
      global approach. This study provides an excellent basis for a comparative
      analysis on feature extraction and detection by animals as diverse as bees and
      mammals.

PMID- 24893309
TI  - Oxidative addition of sigma bonds to an Al(I) center.
AB  - The Al(I) compound NacNacAl (1, NacNac = [ArNC(Me)CHC(Me)NAr](-) and Ar = 2,6
      Pr(i)2C6H3) reacts with H-X (X = H, Si, B, Al, C, N, P, O) sigma bonds of H2,
      silanes, borane (HBpin, pin = pinacolate), allane (NacNacAlH2), phosphine
      (HPPh2), amines, alcohol (Pr(i)OH), and Cp*H (Cp* = pentamethylcyclopentadiene)
      to give a series of hydride derivatives of the four-coordinate aluminum
      NacNacAlH(X), which are characterized herein by spectroscopic methods (NMR and
      IR) and X-ray diffraction. This method allows for the syntheses of the first
      boryl hydride of aluminum and novel silyl hydride and phosphido hydride
      derivatives. In the case of the addition of NacNacAlH2, the reaction is
      reversible, proving the possibility of reductive elimination from the species
      NacNacAlH(X). 

PMID- 24893308
TI  - Variation in seed germination of 134 common species on the eastern Tibetan
      Plateau: phylogenetic, life history and environmental correlates.
AB  - Seed germination is a crucial stage in the life history of a species because it
      represents the pathway from adult to offspring, and it can affect the
      distribution and abundance of species in communities. In this study, we examined
      the effects of phylogenetic, life history and environmental factors on seed
      germination of 134 common species from an alpine/subalpine meadow on the eastern
      Tibetan Plateau. In one-way ANOVAs, phylogenetic groups (at or above order)
      explained 13.0% and 25.9% of the variance in germination percentage and mean
      germination time, respectively; life history attributes, such as seed size,
      dispersal mode, explained 3.7%, 2.1% of the variance in germination percentage
      and 6.3%, 8.7% of the variance in mean germination time, respectively; the
      environmental factors temperature and habitat explained 4.7%, 1.0% of the
      variance in germination percentage and 13.5%, 1.7% of the variance in mean
      germination time, respectively. Our results demonstrated that elevated
      temperature would lead to a significant increase in germination percentage and an
      accelerated germination. Multi-factorial ANOVAs showed that the three major
      factors contributing to differences in germination percentage and mean
      germination time in this alpine/subalpine meadow were phylogenetic attributes,
      temperature and seed size (explained 10.5%, 4.7% and 1.4% of the variance in
      germination percentage independently, respectively; and explained 14.9%, 13.5%
      and 2.7% of the variance in mean germination time independently, respectively).
      In addition, there were strong associations between phylogenetic group and life
      history attributes, and between life history attributes and environmental
      factors. Therefore, germination variation are constrained mainly by phylogenetic
      inertia in a community, and seed germination variation correlated with phylogeny
      is also associated with life history attributes, suggesting a role of niche
      adaptation in the conservation of germination variation within lineages.
      Meanwhile, selection can maintain the association between germination behavior
      and the environmental conditions within a lineage. 

PMID- 24893307
TI  - Genotypes, recombinant forms, and variants of norovirus GII.4 in Gipuzkoa (Basque
      Country, Spain), 2009-2012.
AB  - BACKGROUND: Noroviruses (NoVs) are genetically diverse, with genogroup II-and
      within it-genotype 4 (GII.4) being the most prevalent cause of acute
      gastroenteritis worldwide. The aim of this study was to characterize genogroup II
      NoV causing acute gastroenteritis in the Basque Country (northern Spain) from
      2009-2012. METHODS: The presence of NoV RNA was investigated by reverse
      transcriptase-polymerase chain reaction (RT-PCR) in stool specimens from children
      younger than 15 years old with community-acquired acute gastroenteritis, and from
      hospitalized adults or elderly residents of nursing homes with acute
      gastroenteritis. For genotyping, the open reading frames ORF1 (encoding the
      polymerase) and ORF2 (encoding the major capsid protein) were partially amplified
      and sequenced. Recombinant strains were confirmed by PCR of the ORF1/ORF2
      junction region. RESULTS: NoV was detected in 16.0% (453/2826) of acute
      gastroenteritis episodes in children younger than 2 years, 9.9% (139/1407) in
      children from 2 to 14 years, and 35.8% (122/341) in adults. Of 317 NoVs
      characterized, 313 were genogroup II and four were genogroup I. The GII.4
      variants Den Haag-2006b and New Orleans-2009 predominated in 2009 and 2010-2011,
      respectively. In 2012, the New Orleans-2009 variant was partially replaced by the
      Sydney-2012 variant (GII.Pe/GII.4) and New Orleans-2009/Sydney-2012 recombinant
      strains. The predominant capsid genotype in all age groups was GII.4, which was
      the only genotype detected in outbreaks. The second most frequent genotype was
      GII.3 (including the recently described recombination GII.P16/GII.3), which was
      detected almost exclusively in children. CONCLUSION: Nine different genotypes of
      NoV genogroup II were detected; among these, intergenotype recombinant strains
      represented an important part, highlighting the role of recombination in the
      evolution of NoVs. Detection of new NoV strains, not only GII.4 strains, shortly
      after their first detection in other parts of the world shows that many NoV
      strains can spread rapidly.

PMID- 24893310
TI  - Time-resolved Fourier transform infrared spectroscopy, gravimetry, and
      thermodynamic modeling for a molecular level description of water sorption in
      poly(epsilon-caprolactone).
AB  - Sorption of water in poly(epsilon-caprolactone) (PCL), with specific focus on the
      hydrogen-bonding interactions, has been analyzed by combining ab initio
      calculations, macroscopic thermodynamics modeling, and relevant features emerging
      from spectroscopic and gravimetric measurements. Fourier transform infrared
      (FTIR) data, analyzed by difference spectroscopy, two-dimensional correlation
      spectroscopy, and least-squares curve-fitting analysis associated with
      gravimetric determination of water sorption isotherm provided information on the
      system's behavior and on the molecular interactions established between the
      polymer and the penetrant. A consistent physical picture emerged pointing to the
      presence of two spectroscopically discernible water species (first-shell and
      second-shell layers) that have been quantified. Water molecules are present in
      the form of dimers within the polymer equilibrated with water vapor up to a
      relative humidity of 0.65. At higher humidities, clustering of water sorbed
      molecules starts to take place. The multicomponent nu(OH) band representative of
      absorbed water has been interpreted with the aid of ab initio calculations
      performed on suitably chosen model systems. The outcomes of spectroscopic
      analyses were interpreted at a macroscopic level by modeling the thermodynamics
      of water sorption in PCL based on a nonrandom compressible lattice theory
      accounting for hydrogen-bonding (HB) interactions. Starting from the fitting of
      the gravimetric sorption isotherm, the model provided quantitative estimates for
      the amount of self- and cross-HBs which compare favorably with the FTIR results. 

PMID- 24893311
TI  - Comparison of perioperative outcomes including severe bladder injury between
      monopolar and bipolar transurethral resection of bladder tumors: a population
      based comparison.
AB  - PURPOSE: In this study we used nationwide population based data to compare
      perioperative outcomes, including severe bladder injury, between monopolar and
      bipolar transurethral resection of bladder tumors. MATERIALS AND METHODS: Data of
      patients with clinical T2 or less bladder cancer who underwent monopolar or
      bipolar transurethral bladder tumor resection were collected from 788 hospitals
      in the Japanese Diagnosis Procedure Combination database 2007-2012. One-to-one
      propensity score matching was performed. End points assessed were severe bladder
      injury requiring placement of a drainage tube or repair surgery within 3
      postoperative days, hemostasis procedures consisting of clot removal or
      transurethral coagulation within 3 postoperative days, transfusion, other
      complications, anesthesia duration, postoperative length of stay and total costs.
      Multivariate analyses compared outcomes of bipolar and monopolar transurethral
      bladder tumor resection with gender, age, Charlson comorbidity index, clinical
      stage, hospital volume and hospital academic status as covariates. RESULTS: A
      total of 8,188 pairs were generated. Compared with monopolar transurethral
      bladder tumor resection, bipolar resection was associated with a significantly
      lower incidence of severe bladder injury (0.3% vs 0.6%, OR 0.57), other
      complications (4.6% vs 5.8%, OR 0.78), slightly shorter postoperative stay (mean
      6.4 vs 6.7 days, difference -3.3%) and slightly lower total costs (mean $4,628 vs
      $4,727; difference -1.1%, all p <0.05). There were no differences in
      postoperative hemostasis procedures, transfusion and anesthesia duration.
      CONCLUSIONS: Bipolar transurethral bladder tumor resection was associated with a
      substantially lower incidence of several perioperative complications including
      severe bladder injury. The findings support the benefit of bipolar transurethral
      bladder tumor resection over monopolar resection in real-world clinical practice.

PMID- 24893312
TI  - Identification of different phenotypes of interstitial cells in the upper and
      deep lamina propria of the human bladder dome.
AB  - PURPOSE: There is increasing evidence for an important role of the lamina propria
      in bladder physiology and interstitial cells seem to have a key role in this
      area. Interstitial cells in the upper lamina propria have been studied most
      frequently. We characterized interstitial cells in the deeper lamina propria and
      hypothesized that the 2 interstitial cell populations have different phenotypes
      based on their ultrastructural and immunohistochemical properties. MATERIALS AND
      METHODS: Tissue samples were obtained from macroscopically and microscopically
      normal areas of radical cystectomy specimens. A panel of immunohistochemical
      markers was used to characterize lamina propria interstitial cells. Single/double
      immunohistochemistry/immunofluorescence was performed. At a second phase electron
      microscopy was used to compare upper and deeper lamina propria interstitial
      cells. RESULTS: Overall the phenotype of upper lamina propria interstitial cells
      was vimentin, alpha-smooth muscle actin, caveolin-1 and 2, PDGFRalpha, and
      nonphosphorylated and phosphorylated connexin 43 positive, and CD34 and c-kit
      negative. The overall phenotype of deeper lamina propria interstitial cells was
      vimentin, CD34 and nonphosphorylated connexin 43 positive, and alpha-smooth
      actin, caveolin-1 and 2, PDGFRalpha, phosphorylated connexin 43 and c-kit
      negative. Based on ultrastructural findings upper lamina propria interstitial
      cells were fibroblasts with myoid features and sparse myofibroblasts while deeper
      lamina propria interstitial cells were interstitial cell of Cajal-like cells.
      CONCLUSIONS: To our knowledge this is the first study of 2 main interstitial cell
      populations in the upper and deeper lamina propria of the human bladder with
      distinct ultrastructural and immunohistochemical phenotypes. Future research is
      needed to elucidate whether these morphological findings reflect different roles
      for upper and deeper lamina propria interstitial cells in bladder physiology.

PMID- 24893314
TI  - Nucleophilic substitution dynamics: comparing wave packet calculations with
      experiment.
AB  - The reactive collision of chloride anions and methyl iodide molecules forming
      iodide anions and methyl chloride is a typical example of a concerted bimolecular
      nucleophilic substitution (SN2) reaction. We present wave packet dynamics
      calculations to investigate quantum effects in the collinear gas phase reaction.
      A new type of reduced coordinate system is introduced to allow for an efficient
      solution of the time-dependent Schrodinger equation on an ab initio potential
      energy surface. The reduced coordinates were designed to study the direct rebound
      mechanism under the Walden inversion. Especially the suppressed direct rebound
      mechanism at low collision energies, the quantum effects of the initial state
      preparation and the influence of the CH3 inversion mode are addressed. The
      internal energy distributions of the molecular product are evaluated from the
      wave packet calculations and compared to experimental results obtained with
      crossed-beam velocity map ion imaging. The observed reactivity is discussed in
      light of a dynamical barrier, a concept that is illustrated by the wave packet
      dynamics. 

PMID- 24893315
TI  - Haematological changes in the laboratory rat Rattus norvegicus infected with
      Echinostoma caproni (Trematoda: Echinostomatidae).
AB  - To study possible indirect effects of the infection with intestinal helminths, 12
      Rattus norvegicus (Wistar) were each experimentally exposed to 100 metacercariae
      of Echinostoma caproni, and blood samples were taken weekly up to 4 weeks post
      exposure for comparison with control rats. Values of haematocrit (HCT), red blood
      cells (RBC), platelets (PLT), white blood cells (WBC), haemoglobin (HGB) and
      haematimatrix indices, and mean corpuscular haemoglobin concentrations (MCHC)
      were determined. In addition, leucocyte counts, including lymphocytes,
      neutrophils, monocytes, eosinophils and basophils were analysed. These
      parameters, including the leucocyte counts, showed no significant differences,
      except for MCHC at 4 weeks post-exposure. The present results indicate that in
      rats infected with E. caproni, although eosinophilia did not significantly
      increase, a significant reduction in MCHC was associated with an increase in the
      number of RBC. 

PMID- 24893313
TI  - Extracellular vesicle-mediated transfer of genetic information between the
      hematopoietic system and the brain in response to inflammation.
AB  - Mechanisms behind how the immune system signals to the brain in response to
      systemic inflammation are not fully understood. Transgenic mice expressing Cre
      recombinase specifically in the hematopoietic lineage in a Cre reporter
      background display recombination and marker gene expression in Purkinje neurons.
      Here we show that reportergene expression in neurons is caused by intercellular
      transfer of functional Cre recombinase messenger RNA from immune cells into
      neurons in the absence of cell fusion. In vitro purified secreted extracellular
      vesicles (EVs) from blood cells contain Cre mRNA, which induces recombination in
      neurons when injected into the brain. Although Cre-mediated recombination events
      in the brain occur very rarely in healthy animals, their number increases
      considerably in different injury models, particularly under inflammatory
      conditions, and extend beyond Purkinje neurons to other neuronal populations in
      cortex, hippocampus, and substantia nigra. Recombined Purkinje neurons differ in
      their miRNA profile from their nonrecombined counterparts, indicating
      physiological significance. These observations reveal the existence of a
      previously unrecognized mechanism to communicate RNA-based signals between the
      hematopoietic system and various organs, including the brain, in response to
      inflammation.

PMID- 24893317
TI  - Potential benefits of mindfulness-based interventions in mild cognitive
      impairment and Alzheimer's disease: an interdisciplinary perspective.
AB  - The present article is based on the premise that the risk of developing
      Alzheimer's disease (AD) from its prodromal phase (mild cognitive impairment;
      MCI) is higher when adverse factors (e.g., stress, depression, and metabolic
      syndrome) are present and accumulate. Such factors augment the likelihood of
      hippocampal damage central in MCI/AD aetiology, as well as compensatory
      mechanisms failure triggering a switch toward neurodegeneration. Because of the
      devastating consequences of AD, there is a need for early interventions that can
      delay, perhaps prevent, the transition from MCI to AD. We hypothesize that
      mindfulness-based interventions (MBI) show promise with regard to this goal. The
      present review discusses the associations between modifiable adverse factors and
      MCI/AD decline, MBI's impacts on adverse factors, and the mechanisms that could
      underlie the benefits of MBI. A schematic model is proposed to illustrate the
      course of neurodegeneration specific to MCI/AD, as well as the possible
      preventive mechanisms of MBI. Whereas regulation of glucocorticosteroids,
      inflammation, and serotonin could mediate MBI's effects on stress and depression,
      resolution of the metabolic syndrome might happen through a reduction of
      inflammation and white matter hyperintensities, and normalization of insulin and
      oxidation. The literature reviewed in this paper suggests that the main reach of
      MBI over MCI/AD development involves the management of stress, depressive
      symptoms, and inflammation. Future research must focus on achieving deeper
      understanding of MBI's mechanisms of action in the context of MCI and AD. This
      necessitates bridging the gap between neuroscientific subfields and a cross
      domain integration between basic and clinical knowledge. 

PMID- 24893316
TI  - Estradiol facilitation of cocaine-induced locomotor sensitization in female rats
      requires activation of mGluR5.
AB  - In comparison to men, women exhibit enhanced responsiveness to the stimulating
      and addictive properties of cocaine. A growing body of evidence implicates the
      steroid hormone estradiol in mediating this sex difference, yet the mechanisms
      underlying estradiol enhancement of behavioral responses to cocaine in females
      are not known. Recently, we have found that estrogen receptor alpha (ERalpha)
      functionally couples with the metabotropic glutamate receptor 5 (mGluR5) to
      mediate the effects of estradiol on both cellular activation as well as dendritic
      spine plasticity in brain regions involved in cocaine-induced behavioral
      sensitization. Thus, we sought to determine whether mGluR5 activation is required
      for the facilitative effects of estradiol on locomotor responses to cocaine. To
      test this hypothesis, ovariectomized (OVX) female rats were tested for locomotor
      activity on the first and fifth days of daily systemic injections of cocaine. For
      the 2 days prior to each locomotor test, animals were injected with the mGluR5
      antagonist MPEP (or vehicle) and estradiol (or oil). MPEP treatment blocked the
      facilitative effects of estradiol on cocaine-induced locomotor sensitization,
      without affecting acute responses to cocaine or the inhibitory actions of
      estradiol on weight gain. Considered together, these data indicate that mGluR5
      activation is critical for the actions of estradiol on cocaine-induced behavioral
      sensitization. 

PMID- 24893318
TI  - Light modulation of human sleep depends on a polymorphism in the clock gene
      Period3.
AB  - Non-image-forming (NIF) responses to light powerfully modulate human physiology.
      However, it remains scarcely understood how NIF responses to light modulate human
      sleep and its EEG hallmarks, and if there are differences across individuals.
      Here we investigated NIF responses to light on sleep in individuals genotyped for
      the PERIOD3 (PER3) variable-number tandem-repeat (VNTR) polymorphism. Eighteen
      healthy young men (20-28 years; mean +/- SEM: 25.9 +/- 1.2) homozygous for the
      PER3 polymorphism were matched by age, body-mass index, and ethnicity. The study
      protocol comprised a balanced cross-over design during the winter, during which
      participants were exposed to either light of 40 lx at 6,500 K (blue-enriched) or
      light at 2,500 K (non-blue enriched), during 2h in the evening. Compared to light
      at 2,500 K, light at 6,500 K induced a significant increase in all-night NREM
      sleep slow-wave activity (SWA: 1.0-4.5 Hz) in the occipital cortex for PER3(5/5)
      individuals, but not for PER3(4/4) volunteers. Dynamics of SWA across sleep
      cycles revealed increased occipital NREM sleep SWA for virtually all sleep
      episode only for PER3(5/5) individuals. Furthermore, they experienced light at
      6,500 K as significantly brighter. Intriguingly, this subjective perception of
      brightness significantly predicted their increased occipital SWA throughout the
      sleep episode. Our data indicate that humans homozygous for the PER3(5/5) allele
      are more sensitive to NIF light effects, as indexed by specific changes in sleep
      EEG activity. Ultimately, individual differences in NIF light responses on sleep
      may depend on a clock gene polymorphism involved in sleep-wake regulation.

PMID- 24893321
TI  - Modeling positive Granger causality and negative phase lag between cortical
      areas.
AB  - Different measures of directional influence have been employed to infer effective
      connectivity in the brain. When the connectivity between two regions is such that
      one of them (the sender) strongly influences the other (the receiver), a positive
      phase lag is often expected. The assumption is that the time difference implicit
      in the relative phase reflects the transmission time of neuronal activity.
      However, Brovelli et al. (2004) observed that, in monkeys engaged in processing a
      cognitive task, a dominant directional influence from one area of sensorimotor
      cortex to another may be accompanied by either a negative or a positive time
      delay. Here we present a model of two brain regions, coupled with a well-defined
      directional influence, that displays similar features to those observed in the
      experimental data. This model is inspired by the theoretical framework of
      Anticipated Synchronization developed in the field of dynamical systems.
      Anticipated Synchronization is a form of synchronization that occurs when a
      unidirectional influence is transmitted from a sender to a receiver, but the
      receiver leads the sender in time. This counterintuitive synchronization regime
      can be a stable solution of two dynamical systems coupled in a master-slave
      (sender-receiver) configuration when the slave receives a negative delayed self
      feedback. Despite efforts to understand the dynamics of Anticipated
      Synchronization, experimental evidence for it in the brain has been lacking. By
      reproducing experimental delay times and coherence spectra, our results provide a
      theoretical basis for the underlying mechanisms of the observed dynamics, and
      suggest that the primate cortex could operate in a regime of Anticipated
      Synchronization as part of normal neurocognitive function. 

PMID- 24893320
TI  - Greater striatopallidal adaptive coding during cue-reward learning and food
      reward habituation predict future weight gain.
AB  - Animal experiments indicate that after repeated pairings of palatable food
      receipt and cues that predict palatable food receipt, dopamine signaling
      increases in response to predictive cues, but decreases in response to food
      receipt. Using functional MRI and mixed effects growth curve models with 35
      females (M age=15.5+/-0.9; M BMI=24.5+/-5.4) we documented an increase in BOLD
      response in the caudate (r=.42) during exposure to cues predicting impending
      milkshake receipt over repeated exposures, demonstrating a direct measure of in
      vivo cue-reward learning in humans. Further, we observed a simultaneous decrease
      in putamen (r=-.33) and ventral pallidum (r=-.45) response during milkshake
      receipt that occurred over repeated exposures, putatively reflecting food reward
      habitation. We then tested whether cue-reward learning and habituation slopes
      predicted future weight over 2-year follow-up. Those who exhibited the greatest
      escalation in ventral pallidum responsivity to cues and the greatest decrease in
      caudate response to milkshake receipt showed significantly larger increases in
      BMI (r=.39 and -.69 respectively). Interestingly, cue-reward learning propensity
      and food reward habituation were not correlated, implying that these factors may
      constitute qualitatively distinct vulnerability pathways to excess weight gain.
      These two individual difference factors may provide insight as to why certain
      people have shown obesity onset in response to the current obesogenic environment
      in western cultures, whereas others have not. 

PMID- 24893319
TI  - Predicting indoor heat exposure risk during extreme heat events.
AB  - Increased heat-related morbidity and mortality are expected direct consequences
      of global warming. In the developed world, most fatal heat exposures occur in the
      indoor home environment, yet little is known of the correspondence between
      outdoor and indoor heat. Here we show how summertime indoor heat and humidity
      measurements from 285 low- and middle-income New York City homes vary as a
      function of concurrent local outdoor conditions. Indoor temperatures and heat
      index levels were both found to have strong positive linear associations with
      their outdoor counterparts; however, among the sampled homes a broad range of
      indoor conditions manifested for the same outdoor conditions. Using these models,
      we simulated indoor conditions for two extreme events: the 10-day 2006 NYC heat
      wave and a 9-day event analogous to the more extreme 2003 Paris heat wave. These
      simulations indicate that many homes in New York City would experience
      dangerously high indoor heat index levels during extreme heat events. These
      findings also suggest that increasing numbers of NYC low- and middle-income
      households will be exposed to heat index conditions above important thresholds
      should the severity of heat waves increase with global climate change. The study
      highlights the urgent need for improved indoor temperature and humidity
      management. 

PMID- 24893323
TI  - Effect of atomic interconnects on percolation in single-walled carbon nanotube
      thin film networks.
AB  - The formation of covalent bonds to single-walled carbon nanotube (SWNT) or
      graphene surfaces usually leads to a decrease in the electrical conductivity and
      mobility as a result of the structural rehybridization of the functionalized
      carbon atoms from sp(2) to sp(3). In the present study, we explore the effect of
      metal deposition on semiconducting (SC-) and metallic (MT-) SWNT thin films in
      the vicinity of the percolation threshold and we are able to clearly delineate
      the effects of weak physisorption, ionic chemisorption with charge transfer, and
      covalent hexahapto (eta(6)) chemisorption on these percolating networks. The
      results support the idea that for those metals capable of forming bis-hexahapto
      bonds, the generation of covalent (eta(6)-SWNT)M(eta(6)-SWNT) interconnects
      provides a conducting pathway in the SWNT films and establishes the transition
      metal bis-hexahapto organometallic bond as an electronically conjugating linkage
      between graphene surfaces.

PMID- 24893322
TI  - Combat-related blast exposure and traumatic brain injury influence brain glucose
      metabolism during REM sleep in military veterans.
AB  - Traumatic brain injury (TBI), a signature wound of Operations Enduring and Iraqi
      Freedom, can result from blunt head trauma or exposure to a blast/explosion.
      While TBI affects sleep, the neurobiological underpinnings between TBI and sleep
      are largely unknown. To examine the neurobiological underpinnings of this
      relationship in military veterans, [(18)F]-fluorodeoxyglucose positron emission
      tomography (FDG PET) was used to compare mTBI-related changes in relative
      cerebral metabolic rate of glucose (rCMRglc) during wakefulness, Rapid Eye
      Movement (REM) sleep, and non-REM (NREM) sleep, after adjusting for the effects
      of posttraumatic stress (PTS). Fourteen veterans with a history of blast exposure
      and/or mTBI (B/mTBI) (age 27.5+/-3.9) and eleven veterans with no history (No
      B/mTBI) (age 28.1+/-4.3) completed FDG PET studies during wakefulness, REM sleep,
      and NREM sleep. Whole-brain analyses were conducted using Statistical Parametric
      Mapping (SPM8). Between group comparisons revealed that B/mTBI was associated
      with significantly lower rCMRglc during wakefulness and REM sleep in the
      amygdala, hippocampus, parahippocampal gyrus, thalamus, insula, uncus, culmen,
      visual association cortices, and midline medial frontal cortices. These results
      suggest that alterations in neurobiological networks during wakefulness and REM
      sleep subsequent to B/mTBI exposure may contribute to chronic sleep disturbances
      and differ in individuals with acute symptoms. 

PMID- 24893324
TI  - Metabolomic profiling and genomic study of a marine sponge-associated
      Streptomyces sp.
AB  - Metabolomics and genomics are two complementary platforms for analyzing an
      organism as they provide information on the phenotype and genotype, respectively.
      These two techniques were applied in the dereplication and identification of
      bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge
      Haliclona simulans from Irish waters. Streptomyces strain SM8 extracts showed
      antibacterial and antifungal activity. NMR analysis of the active fractions
      proved that hydroxylated saturated fatty acids were the major components present
      in the antibacterial fractions. Antimycin compounds were initially putatively
      identified in the antifungal fractions using LC-Orbitrap. Their presence was
      later confirmed by comparison to a standard. Genomic analysis of Streptomyces sp.
      SM8 revealed the presence of multiple secondary metabolism gene clusters,
      including a gene cluster for the biosynthesis of the antifungal antimycin family
      of compounds. The antimycin gene cluster of Streptomyces sp. SM8 was inactivated
      by disruption of the antimycin biosynthesis gene antC. Extracts from this mutant
      strain showed loss of antimycin production and significantly less antifungal
      activity than the wild-type strain. Three butenolides, 4,10-dihydroxy-10-methyl
      dodec-2-en-1,4-olide (1), 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (2), and
      4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (3) that had previously been
      reported from marine Streptomyces species were also isolated from SM8. Comparison
      of the extracts of Streptomyces strain SM8 and its host sponge, H. simulans,
      using LC-Orbitrap revealed the presence of metabolites common to both extracts,
      providing direct evidence linking sponge metabolites to a specific microbial
      symbiont. 

PMID- 24893325
TI  - Training the next generation of robotic surgeons using guided mentorship: a
      randomized controlled trial.
AB  - STUDY OBJECTIVE: To evaluate the effect of expert guided mentorship on technical
      score and time for a set of robotic training drills. DESIGN: Prospective
      randomized controlled trial (Canadian Task Force classification I). SETTING:
      Academic institution. SUBJECTS: Fifty trainees in robotic surgery. INTERVENTION:
      Inexperienced trainees underwent either a 20-minute expert guided mentorship
      session or no intervention. The primary outcomes were technical score and time-to
      drill completion for a set of dry lab robotic training drills evaluated at an
      initial and final skills assessment. The t-test, including paired analyses, was
      used to evaluate outcomes. MEASUREMENTS AND MAIN RESULTS: Forty-nine of 50
      trainees (98%) completed the study. There were no significant differences in
      participant characteristics or initial performance between the 2 groups. During
      the final skills assessment, the intervention group demonstrated significantly
      better performance on 1 of 8 objective measures. They had a higher mean score for
      the bead transfer drill when compared with the control group (21.6 vs 19.9; p =
      .03). No differences in time-to-drill completion were noted between the 2 groups.
      Regardless of randomization, all participants had significantly improved scores
      for each of the drills on the final compared with the initial skills assessment
      (p < .01). CONCLUSIONS: Although expert guided mentorship in a dry lab simulation
      environment seems feasible, further investigation is warranted before its
      widespread use because it may be more resource intensive than other teaching
      methods, without consistent objective improvements in technical performance.

PMID- 24893326
TI  - Development, implementation and evaluation of a peer review of teaching (PRoT)
      initiative in nursing education.
AB  - For many years, an area of research in higher education has been emerging around
      the development and implementation of fair and effective peer evaluation
      programs. Recently, a new body of knowledge has developed regarding the
      development and implementation of fair and effective peer evaluation programs
      resulting in formative and summative evaluations. The purpose of this article is
      to describe the development, implementation, and evaluation of a peer review of
      teaching (PRoT) program for nursing faculty, initiated at one small comprehensive
      university in the northeastern United States. Pairs of nursing faculty evaluated
      each other's teaching, syllabi, and course materials after collaborating in a pre
      evaluation conference to discuss goals of the classroom visit. Qualitative data
      gathered in post project focus groups revealed that faculty found their modified
      PRoT process to be a mutually beneficial experience that was more useful,
      flexible and collegial, and less stressful than their previous evaluation
      process.

PMID- 24893328
TI  - High-mobility group box 1 up-regulates aquaporin 4 expression via microglia
      astrocyte interaction.
AB  - To clarify the mechanism of high-mobility group box (HMGB) 1-induced brain edema
      formation, this study focused on the effect of HMGB1 on aquaporin (AQP) 4, a
      water channel, in rat brain. Treatments for 6h with 100-1000ng/ml HMGB1, not
      showing self-toxicity, of primary-cultured rat astrocytes didnot increase AQP4
      mRNA, unexpectedly. In contrast, intracerebroventricular (i.c.v.) injection of
      300ng of HMGB1 significantly increased AQP4 protein after 8h and formed edema
      after 24h in vivo. Thus, we investigated the roles of microglia as well as
      astrocytes. HMGB1 (1000ng/ml) drastically increased interleukin (IL)-1beta in the
      primary-cultured rat microglia after 2h. The exposure of microglia to conditioned
      medium with HMGB1 and 3mM adenosine 5'-triphosphate for 6h significantly
      increased AQP4 mRNA in astrocytes after 6h. Although 1000ng/ml HMGB1 didnot
      induce transfer of nuclear factor (NF)-kappaB into the nucleus in astrocytes
      after 1h, the conditioned medium containing IL-1beta led to its nuclear import.
      As factors likely to be involved in the nuclear import of NF-kappaB besides IL
      1beta, nitric oxide and tumor necrosis factor-alpha didnot contribute under these
      conditions. Finally, i.c.v. injection of 30nmol parthenolide, an NF-kappaB
      inhibitor, reversed 300ng of HMGB1 injection-induced AQP4 protein increase after
      8h in vivo. The effect of parthenolide and the outcomes obtained so far suggest
      that HMGB1 indirectly up-regulates AQP4 expression through diffusible factor(s)
      such as IL-1beta from microglia since HMGB1 by itself didnot affect NF-kappaB
      intracellular localization in astrocytes. 

PMID- 24893329
TI  - Targeted quantitative analysis of synaptic proteins in Alzheimer's disease brain.
AB  - Brain tissue from Alzheimer's disease (AD) patients shows significant loss of
      synapses in selected regions. Synaptic degeneration is the best predictor for
      loss of cognitive functions ante mortem. The molecular mechanisms underlying this
      degeneration remain unknown. Our previous two-dimensional gel-electrophoresis
      proteomics study found that 26 synaptic proteins are differentially expressed in
      Alzheimer's brain. It is difficult to quantify global protein expression using
      this technique because (a) several proteins can migrate together and (b) isoforms
      of the same protein can migrate to different places. The present study estimated
      global synaptic protein levels by label-free multiple reaction monitoring.
      Multiple reaction monitoring is a powerful and sensitive mass spectrometry
      technique that specifically targets multiple protein of interests. The severely
      AD-affected hippocampus was compared with motor cortex, a relatively spared
      region. We targeted ten proteins in autopsy brain based on the earlier study.
      Analytes separated by high performance liquid-chromatography were monitored on a
      hybrid triple quadrupole linear ion trap mass spectrometer in multiple reaction
      monitoring mode. With the use of an internal standard protein, linear and highly
      reproducible (CV<9%) label-free assays were achieved. Data were contrasted with
      the gel-based study to highlight differences and similarities. Significantly
      higher expression levels of peroxiredoxin-1 (may provide antioxidant protection)
      and dihydropyrimidinase-related protein-1 (associated with cytoskeletal
      remodeling) were found in AD hippocampus. Significantly lower levels of
      peroxiredoxin-1 and the energy-related enzymes creatine kinase B and fructose
      bisphosphate aldolase C were found in non-AD hippocampus. Our previously reported
      difference in synaptotagmin expression is probably isoform-specific. These
      findings suggest potential roles of key proteins in synaptic loss in AD, and/or a
      protective mechanism in non-AD brain tissue. 

PMID- 24893330
TI  - The role of TNF-alpha/NF-kappa B pathway on the up-regulation of voltage-gated
      sodium channel Nav1.7 in DRG neurons of rats with diabetic neuropathy.
AB  - Diabetic neuropathy (DN) is a common form of peripheral neuropathy, yet the
      mechanisms responsible for chronic pain in this disease are poorly understood.
      The up-regulation of the expression and function of voltage-gated sodium channel
      Nav1.7 has been implicated in DN, however, the exact mechanism is unclear. In the
      present study, we found that a proportion of streptozotocin (STZ)-treated rats
      suffered from mechanical allodynia and thermal hyperalgesia for a long-lasting
      time. Nav1.7 was up-regulated in spinal dorsal root ganglia (DRG) of rats with
      DN, double immunofluorescence staining showed that the increased Nav1.7 was co
      localized with large and small sized neurons but not satellite glial cells.
      Inhibiting the synthesis of tumor necrosis factor-alpha (TNF-alpha) by
      thalidomide prevented DN, accompanied by strongly blocking the up-regulation of
      Nav1.7, TNF-alpha and p-nucleus factor-kappa B (p-NF-kappaB) in DRG. Intrathecal
      injection of NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly
      attenuated the pain behaviors and over-expression of Nav1.7 in DRG neurons. These
      data suggest that increased TNF-alpha may be responsible for up-regulation of
      Nav1.7 in DRG neurons of rats with DN, and NF-kappaB signal pathway is involved
      in this process. The findings might provide potential target for preventing
      diabetic neuropathy. 

PMID- 24893331
TI  - Segmentation of colon tissue sample images using multiple graphics accelerators.
AB  - Nowadays, processing medical images is increasingly done through using digital
      imagery and custom software solutions. The distributed algorithm presented in
      this paper is used to detect special tissue parts, the nuclei on haematoxylin and
      eosin stained colon tissue sample images. The main aim of this work is the
      development of a new data-parallel region growing algorithm that can be
      implemented even in an environment using multiple video accelerators. This new
      method has three levels of parallelism: (a) the parallel region growing itself,
      (b) starting more region growing in the device, and (c) using more than one
      accelerator. We use the split-and-merge technique based on our already existing
      data-parallel cell nuclei segmentation algorithm extended with a fast,
      backtracking-based, non-overlapping cell filter method. This extension does not
      cause significant degradation of the accuracy; the results are practically the
      same as those of the original sequential region growing method. However, as
      expected, using more devices usually means that less time is needed to process
      the tissue image; in the case of the configuration of one central processing unit
      and two graphics cards, the average speed-up is about 4-6*. The implemented
      algorithm has the additional advantage of efficiently processing very large
      images with high memory requirements. 

PMID- 24893332
TI  - Effects of traditional homemade koumiss on some hematological and biochemical
      characteristics in sedentary men exposed to exercise.
AB  - We evaluated the effects of koumiss on some hematological and biochemical
      characteristics of persons who exercise. Eighteen sedentary males were assigned
      to three equal groups: koumiss (K), koumiss + exercise (KE) and exercise alone
      (E). Leukocytes (WBC), differential leucocyte count, erythrocytes (RBC),
      hemoglobin (HGB), hematocrit (HCT), platelet (PLT), glucose, total cholesterol,
      triglycerides, high density lipoprotein (HDL), aspartate aminotransferase (AST)
      and alanine aminotransferase (ALT) were assessed In blood samples. By the end of
      the study, triglycerides (TG) and cholesterol levels tended to decrease in all
      groups, but the decrease was significant only at day 15 for the KE group. HDL
      tended to be increased in all groups at day 15, but the increase was significant
      only in the KE group. We found that koumiss had beneficial effects on some
      hematological and biochemical characteristics.

PMID- 24893333
TI  - Synergistic dual-ligand doxorubicin liposomes improve targeting and therapeutic
      efficacy of brain glioma in animals.
AB  - Therapeutic outcome for the treatment of glioma was often limited due to low
      permeability of delivery systems across the blood-brain barrier (BBB) and poor
      penetration into the tumor tissue. In order to overcome these hurdles, we
      developed the dual-targeting doxorubicin liposomes conjugated with cell
      penetrating peptide (TAT) and transferrin (T7) (DOX-T7-TAT-LIP) for transporting
      drugs across the BBB, then targeting brain glioma, and penetrating into the
      tumor. The dual-targeting effects were evaluated by both in vitro and in vivo
      experiments. In vitro cellular uptake and three-dimensional tumor spheroid
      penetration studies demonstrated that the system could not only target
      endothelial and tumor monolayer cells but also penetrate tumor to reach the core
      of the tumor spheroids and inhibit the growth of the tumor spheroids. In vivo
      imaging further demonstrated that T7-TAT-LIP provided the highest tumor
      distribution. The median survival time of tumor-bearing mice after administering
      DOX-T7-TAT-LIP was significantly longer than those of the single-ligand
      doxorubicin liposomes and free doxorubicin. In conclusion, the dual-ligand
      liposomes comodified with T7 and TAT possessed strong capability of synergistic
      targeted delivery of payload into tumor cells both in vitro and in vivo, and they
      were able to improve the therapeutic efficacy of brain glioma in animals. 

PMID- 24893334
TI  - Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor
      promoter constructs.
AB  - In current cancer treatment protocols, such as radiation and chemotherapy, side
      effects on normal cells are major obstacles to radical therapy. To avoid these
      side effects, a cancer cell-specific approach is needed. One way to specifically
      target cancer cells is to utilize a cancer specific promoter to express a
      cytotoxic gene (suicide gene therapy) or a viral gene required for viral
      replication (oncolytic virotherapy). For this purpose, the selected promoter
      should have minimal activity in normal cells to avoid side effects, and high
      activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In
      contrast to the AFP, CEA and PSA promoters, which have high activity only in a
      limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide
      variety of cancers. This is based on the mechanism of carcinogenesis. Defects in
      the RB pathway and activation of the transcription factor E2F, the main target of
      the RB pathway, are observed in almost all cancers. Consequently, the E2F1
      promoter, which is mainly regulated by E2F, has high activity in wide variety of
      cancers. However, E2F is also activated by growth stimulation in normal growing
      cells, suggesting that the E2F1 promoter may also be highly active in normal
      growing cells. In contrast, we found that the tumor suppressor ARF promoter is
      activated by deregulated E2F activity, induced by forced inactivation of pRB, but
      does not respond to physiological E2F activity induced by growth stimulation. We
      also found that the deregulated E2F activity, which activates the ARF promoter,
      is detected only in cancer cell lines. These observations suggest that ARF
      promoter is activated by E2F only in cancer cells and therefore may be more
      cancer cell-specific than E2F1 promoter to drive gene expression. We show here
      that the ARF promoter has lower activity in normal growing fibroblasts and shows
      higher cancer cell-specificity compared to the E2F1 promoter. We also demonstrate
      that adenovirus expressing HSV-TK under the control of the ARF promoter shows
      lower cytotoxicity than that of the E2F1 promoter, in normal growing fibroblasts
      but has equivalent cytotoxicity in cancer cell lines. These results suggest that
      the ARF promoter, which is specifically activated by deregulated E2F activity, is
      an excellent candidate to drive therapeutic cytotoxic gene expression,
      specifically in cancer cells. 

PMID- 24893335
TI  - The effects of the arm swing on biomechanical and physiological aspects of roller
      ski skating.
AB  - This study analyzed the biomechanical and physiological effects of the arm swing
      in roller ski skating, and compared leg-skating (i.e. ski skating without poles)
      using a pronounced arm swing (SWING) with leg-skating using locked arms (LOCKED).
      Sixteen elite male cross-country skiers performed submaximal stages at 10, 15 and
      20kmh(-1) on a 2% inclined treadmill in the two techniques. SWING demonstrated
      higher peak push-off forces and a higher force impulse at all speeds, but a
      longer cycle length only at the highest speed (all P<.05), indicating a lower
      force effectiveness with SWING at the two lowest speeds. Additionally, the
      flexion-extension movement in the lower limbs was more pronounced for SWING.
      Oxygen uptake was higher for SWING at the two lowest speeds (both P<.05) without
      any differences in blood lactate. At the highest speed, oxygen uptake did not
      differ between SWING and LOCKED, but the RER, blood lactate and ventilation were
      lower with SWING (all P<.05). Taken together, these results demonstrate that
      utilizing the arm swing in roller ski skating increases the ski forces and
      aerobic energy cost at low and moderate speeds, whereas the greater forces at
      high speed lead to a longer cycle length and smaller anaerobic contribution. 

PMID- 24893337
TI  - Analysis of chemosensory gene families in the beetle Monochamus alternatus and
      its parasitoid Dastarcus helophoroides.
AB  - We assembled antennal transcriptomes of pest Monochamus alternatus and its
      parasitoid Dastarcus helophoroides to identify the members of the major
      chemosensory multi-gene families. Gene ontology (GO) annotation indicated that
      the relative abundance of transcripts associated with specific GO terms was
      highly similar in the two species. In chemosensory gene families, we identified
      52 transcripts encoding putative odorant-binding proteins (OBPs), 19 chemosensory
      proteins (CSPs), 10 olfactory receptors (ORs), 8 ionotropic receptors (IRs), 2
      gustatory receptors (GRs), and 5 sensory neuron membrane proteins (SNMPs) in
      these two transcriptomes. Predicted protein sequences were compared with
      Dendroctonus ponderosae, Tribolium castaneum and Drosophila melanogaster. The
      results of phylogenetic trees showed that some clusters included only OBPs or
      CSPs from D. helophoroides, some clusters included only OBPs or CSPs from M.
      alternatus, while some clusters included OBPs or CSPs from both M. alternatus and
      D. helophoroides. The identification of the chemosensory genes and the
      phylogenetic relationship of these genes between two species might provide new
      ideas for controlling M. alternatus and improving current strategies for
      biological control.

PMID- 24893338
TI  - Cryptosporidium parvum has an active hypusine biosynthesis pathway.
AB  - The protozoan parasite Cryptosporidium parvum causes severe enteric infection and
      diarrheal disease with substantial morbidity and mortality in untreated AIDS
      patients and children in developing or resource-limited countries. No fully
      effective treatment is available. Hypusination of eIF5A is an important post
      translational modification essential for cell proliferation. This modification
      occurs in a two step process catalyzed by deoxyhypusine synthase (DHS) followed
      by deoxyhypusine hydroxylase. An ORF of 1086bp was identified in the C. parvum
      (Cp) genome which encodes for a putative polypeptide of 362 amino acids. The
      recombinant CpDHS protein was purified to homogeneity and used to probe the
      enzyme's mechanism, structure, and inhibition profile in a series of kinetic
      experiments. Sequence analysis and structural modeling of CpDHS were performed to
      probe differences with respect to the DHS of other species. Unlike Leishmania,
      Trypanosomes and Entamoeba, Cryptosporidium contains only a single gene for DHS.
      Phylogenetic analysis shows that CpDHS is more closely related to apicomplexan
      DHS than kinetoplastid DHS. Important residues that are essential for the
      functioning of the enzyme including NAD(+) binding residues, spermidine binding
      residues and the active site lysine are conserved between CpDHS and human DHS.
      N(1)-guanyl-1,7-diaminoheptane (GC7), a potent inhibitor of DHS caused an
      effective inhibition of infection and growth of C. parvum in HCT-8 cells. 

PMID- 24893341
TI  - The gap between academia and practice: reflections from a nurse researcher.

PMID- 24893339
TI  - Evolution of parasitism in kinetoplastid flagellates.
AB  - Kinetoplastid protists offer a unique opportunity for studying the evolution of
      parasitism. While all their close relatives are either photo- or phagotrophic, a
      number of kinetoplastid species are facultative or obligatory parasites,
      supporting a hypothesis that parasitism has emerged within this group of
      flagellates. In this review we discuss origin and evolution of parasitism in
      bodonids and trypanosomatids and specific adaptations allowing these protozoa to
      co-exist with their hosts. We also explore the limits of biodiversity of
      monoxenous (one host) trypanosomatids and some features distinguishing them from
      their dixenous (two hosts) relatives. 

PMID- 24893340
TI  - Gene disruption reveals a dispensable role for plasmepsin VII in the Plasmodium
      berghei life cycle.
AB  - Plasmepsins (PM), aspartic proteases of Plasmodium, comprises a family of ten
      proteins that perform critical functions in Plasmodium life cycle. Except VII and
      VIII, functions of the remaining plasmepsin members have been well characterized.
      Here, we have generated a mutant parasite lacking PM VII in Plasmodium berghei
      using reverse genetics approach. Systematic comparison of growth kinetics and
      infection in both mosquito and vertebrate host revealed that PM VII depleted
      mutants exhibited no defects in development and progressed normally throughout
      the parasite life cycle. These studies suggest a dispensable role for PM VII in
      Plasmodium berghei life cycle. 

PMID- 24893342
TI  - TwitterTM as a study prompt: engaging adult learners on the go.

PMID- 24893343
TI  - Integrating national patient safety initiatives into prelicensure clinical
      learning.

PMID- 24893346
TI  - Consideration of criteria required for assignment of a (skin) sensitiser a
      substance of very high concern (SVHC) under the REACH regulation.
AB  - The identification, characterisation, risk assessment and risk management of
      materials that cause allergic sensitisation is an important requirement for human
      health protection. It has been proposed that for some chemical and protein
      allergens, and in particular for those that cause sensitisation of the
      respiratory tract (associated with occupational asthma), it may be appropriate to
      regard them as Substances of Very High Concern (SVHC) under the provisions of
      REACH (Registration, Evaluation, Authorisation and restriction of CHemicals). We
      have argued previously that categorisation of sensitising agents as SVHC should
      be used only in exceptional circumstances. In the present article, the subject of
      SVHC is addressed from another perspective. Here the information that would be
      required to provide a compelling case for categorisation of a skin sensitising
      substance as a SVHC is considered. Three skin sensitising chemicals have been
      identified to serve as working examples. These are chromate, a potent contact
      allergen, and the skin sensitisers formaldehyde and isoeugenol. The key criterion
      influencing the decision regarding a skin sensitiser being categorised as SVHC is
      the extent to which impacts on the quality of life are reversible. Consequently,
      SVHC categorisation for skin sensitising chemicals should be used only in
      exceptional circumstances.

PMID- 24893344
TI  - Age-related differences in effective connectivity of brain regions involved in
      Japanese kanji processing with homophone judgment task.
AB  - Reading is a complex process involving neural networks in which connections may
      be influenced by task demands and other factors. We employed functional magnetic
      resonance imaging and dynamic causal modeling to examine age-related influences
      on left-hemispheric kanji reading networks. During a homophone judgment task,
      activation in the middle frontal gyrus, and dorsal and ventral inferior frontal
      gyri were identified, representing areas involved in orthographic, phonological,
      and semantic processing, respectively. The young adults showed a preference for a
      semantically-mediated pathway from orthographic inputs to the retrieval of
      phonological representations, whereas the elderly preferred a direct connection
      from orthographic inputs to phonological lexicons prior to the activation of
      semantic representations. These sequential pathways are in line with the lexical
      semantic and non-semantic routes in the dual-route cascaded model. The shift in
      reading pathways accompanied by slowed reaction time for the elderly might
      suggest age-related declines in the efficiency of network connectivity. 

PMID- 24893345
TI  - Changes in cardiopulmonary exercise testing parameters following continuous flow
      left ventricular assist device implantation and heart transplantation.
AB  - BACKGROUND: Reduced exercise tolerance from impaired cardiac output is an
      important criterion for left ventricular assist device (LVAD) implantation.
      However, little is known about how exercise capacity changes after LVAD and how
      changes compare with patients undergoing heart transplantation. METHODS AND
      RESULTS: We compared changes in cardiopulmonary exercise testing performed pre-
      and postoperatively in patients who underwent HeartMate II LVAD implantation (n =
      25) and heart transplantation (n = 74) at the Mayo Clinic in Rochester,
      Minnesota, between 2007 and 2012. Preoperatively, patients undergoing LVAD and
      transplant had markedly reduced exercise time (mean 5.1 minutes [45% predicted]
      and 5.0 minutes [44% predicted], respectively), low peak oxygen consumption (VO2;
      mean 11.5 mL . kg . min [43% predicted] and 11.9 mL . kg . min [38% predicted]),
      and abnormal ventilatory gas exchange (ratio of minute ventilation to carbon
      dioxide production [VE/VCO2] nadir 39.4 and 37.4). After LVAD and transplant,
      there were similar improvements in exercise time (mean Delta +1.2 vs. 1.7
      minutes, respectively, P = .27) and VE/VCO2 nadir (mean Delta -3.7 vs. -4.2, P =
      .74). However, peak VO2 increased posttransplant but did not change post-LVAD
      (mean Delta +5.4 vs. +0.9 mL . kg . min, respectively, P < .001). Most patients
      (72%) had a peak VO2 < 14 mL . kg . min post-LVAD. CONCLUSIONS: Although
      improvements in exercise capacity and gas exchange are seen after LVAD and heart
      transplant, peak VO2 doesn't improve post-LVAD and remains markedly abnormal in
      most patients.

PMID- 24893347
TI  - Second generation sequencing of three STRs D3S1358, D12S391 and D21S11 in Danes
      and a new nomenclature for sequenced STR alleles.
AB  - Second generation sequencing (SGS) may revolutionize the field of forensic STR
      typing. Two of the essential requirements for implementation of an SGS based
      approach for forensic investigations are (1) establishment of adequate frequency
      databases and (2) adoption of a new STR nomenclature. We report the STR sequences
      and allele frequencies of three STR loci: D3S1358, D12S391 and D21S11 in 197
      unrelated Danes. We used a new STR nomenclature that depicts the locus name used
      in forensic genetics, the length of the repeat region divided by the repeat
      length (typically 4 nucleotides) and detailed sequence information of possible
      sub-repeats and SNPs within the amplified fragment. 

PMID- 24893336
TI  - Seasonal changes in dominant bacterial taxa from acidic peatlands of the Atlantic
      Rain Forest.
AB  - The acidic peatlands of southern Brazil are essential for maintenance of the
      Atlantic Rain Forest, one of the 25 hot-spots of biodiversity in the world. While
      these ecosystems are closely linked to conservation issues, their microbial
      community ecology and composition remain unknown. In this work, histosol samples
      were collected from three acidic peatland regions during dry and rainy seasons
      and their chemical and microbial characteristics were evaluated. Culturing and
      culture-independent approaches based on SSU rRNA gene pyrosequencing were used to
      survey the bacterial community and to identify environmental factors affecting
      the biodiversity and microbial metabolic potential of the Brazilian peatlands.
      All acidic peatlands were dominated by the Acidobacteria phylum (56-22%) followed
      by Proteobacteria (28-12%). The OTU richness of these phyla and the abundance of
      their Gp1, Gp2, Gp3, Gp13, Rhodospirillales and Caulobacteriales members varied
      according to the period of collection and significantly correlated with the rainy
      season. However, despite changes in acidobacterial and proteobacterial
      communities, rainfall did not affect the microbial metabolic potential of the
      southern Brazilian Atlantic Rain Forest peatlands, as judged by the metabolic
      capabilities of the microbial community. 

PMID- 24893348
TI  - Forensic animal DNA typing: Allele nomenclature and standardization of 14 feline
      STR markers.
AB  - Since the domestic cat (Felis catus) has become one of the most popular pets and
      owners usually develop a close relationship to their cats, it is necessary to
      take traces of cats into account for forensic casework. For this purpose feline
      short tandem (STR) repeat markers have been investigated in several earlier
      studies, but no detailed description of sequence data, allelic variations or a
      repeat-based nomenclature is available. The aim of the study was to provide a
      suggestion for the allele nomenclature of 14 cat STR markers according to the
      recommendations of the International Society for Forensic Genetics (ISFG) for
      human DNA typing and to present a standardized system for a secure DNA typing of
      samples. Samples of 122 unrelated cats from a local animal shelter and private
      owners in Germany were used to generate a population database with allele
      frequencies and to analyze the tandemly repeated sequence variations within the
      alleles of each STR marker. These markers could be grouped into two STR classes:
      simple repeat STRs and complex STRs (some with the supplement highly complex),
      consisting of di- and tetranucleotide repeat motifs. After analyzing the repeat
      structure and elaborating a repeat based nomenclature, allelic ladders of common
      and rarely occurring alleles for each marker were designed to enable accurate
      typing of alleles that differ in fragment length and to facilitate data exchange.

PMID- 24893349
TI  - Biopesticides from plants: Calceolaria integrifolia s.l.
AB  - The effects of persistent organic pollutants (POPs) on humans and biodiversity
      are multiple and varied. Nowadays environmentally-friendly pesticides are
      strongly preferred to POPs. It is noteworthy that the crop protection role of
      pesticides and other techniques, i.e. biopesticides, plant extracts, prevention
      methods, organic methods, evaluation of plant resistance to certain pests under
      an integrated pest management (IPM), could improve the risks and benefits which
      must be assessed on a sound scientific basis. For this directive it is crucial to
      bring about a significant reduction in the use of chemical pesticides, not least
      through the promotion of sustainable alternative solutions such as organic
      farming and IPM. Biopesticides are derived from natural materials such as
      animals, plants, bacteria, and certain minerals. Most of them are biodegradable
      in relatively short periods of time. On this regard, substances from Calceolaria
      species emerge as a strong alternative to the use of POPs. The American genus
      Calceolaria species are regarded both as a notorious weeds and popular ornamental
      garden plants. Some have medicinal applications. Other taxa of Calceolaria are
      toxic to insects and resistant to microbial attack. These properties are probably
      associated with the presence of terpenes, iridoids, flavonoids, naphthoquinones
      and phenylpropanoids previously demonstrated to have interesting biological
      activities. In this article a comprehensive evaluation of the potential
      utilization of Calceolaria species as a source of biopesticides is made. The
      chemical profile of selected members of the Chilean Calceolaria integrifolia
      sensu lato complex represents a significant addition to previous studies. New
      secondary metabolites were isolated, identified and tested for their antifeedant,
      insect growth regulation and insecticidal activities against Spodoptera
      frugiperda and Drosophila melanogaster. These species serve as a model of insect
      pests using conventional procedures. Additionally, bactericidal and fungicidal
      activity were determined. Dunnione mixed with gallic acid was the most active
      fungistatic and fungicidal combination encountered. Several compounds as
      isorhamnetin, combined with ferulic and gallic acid quickly reduced cell
      viability, but cell viability was recovered quickly and did not differ from that
      of the control. The effect of these mixtures on cultures of Aspergillus niger,
      Fusarium moniliforme, Fusarium sporotrichum, Rhizoctonia solani, and Trichophyton
      mentagrophytes, was sublethal. However, when fungistatic isorhamnetin and
      dunnione were combined with sublethal amounts of both ferulic and gallic acid,
      respectively, strong fungicidal activity against theses strains was observed.
      Thus, dunnione combined with gallic acid completely restricted the recovery of
      cell viability. This apparent synergistic effect was probably due to the blockade
      of the recovery process from induced-stress. The same series of phenolics
      (iridoids, flavonoids, naphthoquinones and phenylpropanoids) were also tested
      against the Gram-negative bacteria Escherichia coli, Enterobacter agglomerans,
      and Salmonella typhi, and against the Gram-positive bacteria Bacillus subtilis,
      Sarcinia lutea, and Staphylococcus aureus and their effects compared with those
      that of kanamycin. Mixtures of isorhamnetin/dunnione/kaempferol/ferulic/gallic
      acid in various combinations were found to have the most potent bactericidal and
      fungicidal activity with MFC between 10 and 50 MUg/ml. Quercetin was found to be
      the most potent fungistatic single compound with an MIC of 15 ug/ml. A time-kill
      curve study showed that quercetin was fungicidal against fungi assayed at any
      growth stage. This antifungal activity was slightly enhanced by combination with
      gallic acid. The primary antifungal action of the mixtures assayed likely comes
      from their ability to act as nonionic surfactants that disrupt the function of
      native membrane-associated proteins. Hence, the antifungal activity of
      isorhamnetin and other O-methyl flavonols appears to be mediated by biophysical
      processes. Maximum activity is obtained when the balance between hydrophilic and
      hydrophobic portions of the molecules of the mixtures becomes the most
      appropriate. Diterpenes, flavonoids, phenylpropanoids, iridoids and phenolic
      acids were identified by chromatographic procedures (HPLC-DAD), ESI-MS, and NMR
      hyphenated techniques.

PMID- 24893350
TI  - Effects of reflux laryngitis on non-nutritive swallowing in newborn lambs.
AB  - Reflux laryngitis in infants may be involved not only in laryngeal disorders, but
      also in disorders of cardiorespiratory control through its impact on laryngeal
      function. Our objective was to study the effect of reflux laryngitis on non
      nutritive swallowing (NNS) and NNS-breathing coordination. Two groups of six
      newborn lambs, randomized into laryngitis and control groups, were surgically
      instrumented for recording states of alertness, swallowing and cardiorespiratory
      variables without sedation. A mild to moderate reflux laryngitis was induced in
      lambs from the experimental group. A significant decrease in the number of NNS
      bursts and apneas was observed in the laryngitis group in active sleep (p=0.03).
      In addition, lower heart and respiratory rates, as well as prolonged apnea
      duration (p<0.0001) were observed. No physiologically significant alterations in
      NNS-breathing coordination were observed in the laryngitis group. We conclude
      that a mild to moderate reflux laryngitis alters NNS burst frequency and
      autonomous control of cardiac activity and respiration in lambs. 

PMID- 24893351
TI  - Norovirus: targets and tools in antiviral drug discovery.
AB  - The development of antiviral strategies to treat or prevent norovirus infections
      is a pressing matter. Noroviruses are the number 1 cause of acute
      gastroenteritis, of foodborne illness, of sporadic gastroenteritis in all age
      groups and of severe acute gastroenteritis in children less than 5 years old
      seeking medical assistance [USA/CDC]. In developing countries, noroviruses are
      linked to significant mortality (~200,000 children <5 years old). Noroviruses are
      a major culprit for the closure of hospital wards, and associated with increased
      hospitalization and mortality among the elderly. Transplant patients have
      significant risk of acquiring persistent norovirus gastroenteritis. Control and
      prevention strategies are limited to the use of disinfectants and hand
      sanitizers, whose efficacy is frequently insufficient. Hence, there is an ample
      need for antiviral treatment and prophylaxis of norovirus infections. The fact
      that only a handful of inhibitors of norovirus replication have been reported can
      largely be attributable to the hampering inability to cultivate human noroviruses
      in cell culture. The Norwalk replicon-bearing cells and the murine norovirus
      infected cell lines are the available models to assess in vitro antiviral
      activity of compounds. Human noroviruses have been shown to replicate (to some
      extent) in mice, calves, gnotobiotic pigs, and chimpanzees. Infection of
      interferon-deficient mice with the murine norovirus results in virus-induced
      diarrhea. Here we review recent developments in understanding which norovirus
      proteins or host cell factors may serve as targets for inhibition of viral
      replication. Given the recent advances, significant progress in the search for
      antiviral strategies against norovirus infections is expected in the upcoming
      years.

PMID- 24893352
TI  - Superior oblique tucking for treatment of superior oblique palsy.
AB  - PURPOSE: To investigate the efficacy and safety of isolated superior oblique
      tucking in the treatment of congenital superior oblique palsy. METHODS: Twenty
      one patients with unilateral congenital superior oblique palsy and lax superior
      oblique tendon underwent isolated superior oblique tucking and retrospective
      analysis of the amount of tucking procedure, preoperative and postoperative
      vertical deviation in the primary position and reading position, abnormal head
      posture, ocular motility, and corrected objective torsion. Patients were
      evaluated before and 6 to 12 months after surgery. RESULTS: The average vertical
      deviation in the primary position was 10.9 +/- 3.3 prism diopters (PD) before
      surgery and 1.5 +/- 2.6 PD after surgery (n = 21, P < .05). The average vertical
      deviation in the reading position was 15.6 +/- 3.6 PD before surgery and 2.6 +/-
      3.1 PD after surgery (P < .05). The average corrected vertical deviation was 9.9
      +/- 3.2 PD in the primary position and 13.0 +/- 3.4 PD in the reading position (P
      < .05). The amount of tucking ranged from 5 to 12 mm (mean: 8.3 +/- 2.3 mm),
      which was not related to the corrected vertical deviation in the primary and
      reading positions, the preoperative vertical deviation in the reading position,
      or the corrected objective torsion. After surgery, all patients had head posture
      that was normal or less than 5 degrees . Unremarkable superior oblique
      underaction and negative head tilt test were found in all patients after surgery.
      All patients had mild Brown syndrome after surgery, but none were symptomatic.
      CONCLUSIONS: Isolated superior oblique tucking is an efficient and safe procedure
      for treatment of superior oblique palsy with hyperdeviation less than 15 PD in
      the primary position and remarkable superior oblique underaction. The superior
      oblique forced duction test was the most important criterion for planning
      surgery.

PMID- 24893353
TI  - Palliative care for terminally ill individuals with schizophrenia.
AB  - Individuals with schizophrenia are often medically undertreated and experience
      symptoms that interfere with communication and the capacity to make medical
      decisions. These issues complicate quality end-of-life care for this population
      and are of particular concern for hospice and palliative care nurses and health
      care providers. This article presents a case study of a terminally ill patient
      with schizophrenia. It is divided into a series of vignettes; each vignette
      presents a common clinical issue encountered by the palliative care team.
      Interventions suggested in the literature and those used by team members when
      working with the patient are discussed.

PMID- 24893354
TI  - Optical quality and intraocular scattering after femtosecond laser small incision
      lenticule extraction.
AB  - PURPOSE: To investigate objective optical quality and changes in light scatter
      after femtosecond laser small incision lenticule extraction (SMILE) for moderate
      to high myopia correction. METHODS: Prospective clinical study of 66 eyes of 66
      patients (23 males, 43 females) with a mean age of 28.67 +/- 6.62 years, mean
      spherical refraction of -6.06 +/- 1.57 diopters, and mean cylindrical refraction
      of -0.68 +/- 0.46 diopters. Every patient had a 3-month follow-up after a
      standard SMILE procedure. An optical quality analysis system was used to measure
      modulation transfer function cutoff frequency (MTFcutoff), Strehl2D ratio, and
      objective scatter index (OSI). RESULTS: At 3 months postoperatively, mean
      spherical equivalent was 0.03 +/- 0.24 diopters and corrected distance visual
      acuities of all patients were equal to or better than preoperative values, with a
      mean safety index of 1.12 +/- 0.17 (range: 0.80 to 1.50) and mean efficacy index
      of 1.18 +/- 0.21 (range: 0.80 to 1.50). Mean OSI increased from 0.75
      preoperatively to 1.09 at 20 days postoperatively (P < .05), and gradually
      declined to 0.94 at 40 days and 0.82 at 3 months postoperatively (P > .05).
      MTFcutoff and Strehl2D ratio did not change significantly compared with
      preoperative values (P > .05). Multiple linear regression analysis revealed that
      preoperative OSI was significantly correlated with optical quality at 3 months.
      Patients with less preoperative OSI tended to acquire higher MTFcutoff (b = 
      8.61) and lower OSI (b = 0.65) (P < .05). CONCLUSIONS: SMILE had little impact on
      retinal image quality after myopia correction. Postoperative OSI showed a
      temporary increase and then returned to normal.

PMID- 24893355
TI  - Lenticule thickness readout for small incision lenticule extraction compared to
      artemis three-dimensional very high-frequency digital ultrasound stromal
      measurements.
AB  - PURPOSE: To evaluate the accuracy of the lenticule thickness readout for small
      incision lenticule extraction (SMILE) with the VisuMax femtosecond laser (Carl
      Zeiss Meditec, Jena, Germany). METHODS: Artemis very high-frequency digital
      ultrasound (ArcScan, Inc., Morrison, CO) measurements were obtained before and 3
      months after SMILE in 70 eyes of 37 patients. The Artemis measured lenticule
      thickness was calculated as the maximum difference in stromal thickness before
      and after treatment. Comparative statistics and linear regression analysis were
      performed between the VisuMax readout lenticule thickness and Artemis measured
      maximum stromal change. Central epithelial thickness was measured and a similar
      analysis was performed using corneal thickness. Variability of the data were
      compared to ablation depths for a matched group of eyes from a previously
      published LASIK population treated with the MEL80 excimer laser (Carl Zeiss
      Meditec). RESULTS: The mean maximum myopic meridian treated was -7.81 +/- 2.33
      diopters (range: -2.25 to -12.50 diopters). On average, the VisuMax readout
      lenticule depth was 8.2 +/- 8.0 MUm thicker (range: -8 to +29 MUm) than the
      Artemis measured stromal change (P < .001). On average, central epithelial
      thickness was 15.0 +/- 5.2 MUm thicker (range: 5 to 30 MUm) after the procedure.
      The VisuMax readout lenticule thickness was 23.2 +/- 10.9 MUm thicker (range: +5
      to +49 MUm) than the Artemis measured corneal thickness change. The R(2) of 0.868
      for the SMILE group was higher than 0.738 for the LASIK group (P = .015).
      CONCLUSIONS: The accuracy of SMILE lenticule thickness was found to be higher
      than actual measured stromal thickness change; however, predictability for SMILE
      lenticule thickness appeared higher than predictability for excimer laser
      ablation depth. The VisuMax readout lenticule depth was found to be 8 MUm thicker
      than the achieved stromal change. This can be partly explained by alignment
      errors between preoperative and postoperative scans. However, this appears to
      show some biomechanical changes occur after SMILE.

PMID- 24893356
TI  - Add-on sulcus-based versus primary in-the-bag multifocal intraocular lens:
      intraindividual study.
AB  - PURPOSE: To compare the clinical outcomes of add-on sulcus-based multifocal and
      standard in-the-bag multifocal intraocular lens (IOL) implantation. METHODS:
      Twenty-one patients with unilateral monofocal pseudophakia underwent add-on
      sulcus-based Acri. LISA 536D multifocal IOL (Carl Zeiss Meditec, Jena, Germany)
      implantation (add-on multifocal IOL group) and contralateral phacoemulsification
      with in-the-bag Acri.LISA 376D multifocal IOL (Carl Zeiss Meditec) implantation
      (primary multifocal IOL group). Uncorrected distance visual acuity, uncorrected
      near visual acuity, corrected distance visual acuity, distance-corrected near
      visual acuity, photopic (90 cd/m(2)) distance, near contrast sensitivity, mesopic
      (5 cd/m(2)) distance contrast sensitivity with and without glare, wavefront
      aberrations, and complications were measured 6 months postoperatively. RESULTS:
      Primary in-the-bag multifocal IOLs provided slightly but significantly better
      uncorrected distance visual acuity (0.08 +/- 0.10 vs 0.17 +/- 0.15 logMAR, P =
      .028), uncorrected near visual acuity (0.09 +/- 0.17 vs 0.18 +/- 0.11 logMAR, P =
      .005), and corrected distance visual acuity (0.01 +/- 0.04 vs 0.04 +/- 0.05
      logMAR, P = .038). There were no significant differences in distance-corrected
      near visual acuity, photopic or mesopic contrast sensitivity under different
      conditions, and wavefront aberrations. Complications included pigment dispersion
      in one eye (4.8%) and pupillary capture in 2 eyes (9.5%) of the add-on multifocal
      IOL group. CONCLUSIONS: The secondary add-on sulcus-based multifocal IOL provided
      useful pseudoaccommodation with vision quality similar to the primary in-the-bag
      multifocal IOL. The technique should be considered in patients diagnosed as
      having unilateral or bilateral monofocal pseudophakia seeking near spectacle
      independence.

PMID- 24893357
TI  - Evaluating the short-term results of KAMRA inlay implantation using real-time
      optical coherence tomography-guided femtosecond laser technology.
AB  - PURPOSE: To evaluate the outcomes from using real-time optical coherence
      tomography (OCT)-guided femtosecond laser technology for pocket creation for
      KAMRA inlay (Acufocus, Inc., Irvine, CA) implantation surgery. METHODS: One
      hundred fifty-one eyes underwent KAMRA inlay implantation using the real-time OCT
      guided femtosecond laser for pocket creation. All patients had a history of prior
      LASIK. Uncorrected distance visual acuity, corrected distance visual acuity,
      uncorrected near visual acuity, corrected near visual acuity, and manifest
      refraction spherical equivalent were evaluated preoperatively and
      postoperatively. The follow-up period was 3 months. RESULTS: Mean manifest
      refraction spherical equivalent, uncorrected distance visual acuity, and
      uncorrected near visual acuity changed from -0.18 +/- 0.33 to -0.95 +/- 0.64,
      20/16 to 20/20, and J8 to J2, respectively. Corrected distance visual acuity and
      corrected near visual acuity remained stable before and after KAMRA inlay
      implantation, 20/12 and J1, respectively. CONCLUSIONS: Using real-time OCT-guided
      femtosecond laser technology increases the safety and accuracy of corneal KAMRA
      inlay implantation surgery with a history of prior LASIK with excellent visual
      and refractive outcomes.

PMID- 24893358
TI  - Comparison of surgically induced astigmatism following iris-claw PIOL insertion
      with scleral, limbal, or corneal incisions.
AB  - PURPOSE: To compare surgically induced astigmatism (SIA) based on incision site
      and evaluate the clinical results and astigmatic stability of iris-claw phakic
      intraocular lens (Artisan lens; Ophtec BV, Groningen, Netherlands) implantation.
      METHODS: Eighty-five eyes of 53 patients with myopia who underwent Artisan lens
      implantation with a 6.2-mm incision and follow-up of 6 months were
      retrospectively observed. SIA was assessed using keratometric astigmatism at 6
      months postoperatively for the incision sites of the sclera, limbus, and cornea,
      and the efficacy, safety, predictability, and astigmatic stability were also
      calculated. RESULTS: SIA obtained using Naeser's polar method (KP[90]SIA) was 
      0.48 +/- 0.35 for scleral incisions, -0.99 +/- 0.35 for limbal incisions, and 
      1.14 +/- 0.54 for corneal incisions. Corresponding net astigmatism values, as
      calculated with KP(90)SIA and KP(135)SIA, were 0.70 +/- 0.48 (177 degrees ), 1.04
      +/- 0.37 (175 degrees ), and 1.21 +/- 0.57 (1 degrees ), respectively, with SIA
      increasing the nearer the incision was to the cornea center. Six months after
      surgery, the efficacy index was 1.03 and the safety index was 1.08. Ninety-eight
      percent of patients were within 1.50 diopters of attempted refraction.
      CONCLUSIONS: The values of SIA after Artisan lens insertion showed significant
      differences among three incision locations, despite the absence of significant
      differences in preoperative steep corneal axis astigmatism values at the incision
      locations. It would be applicable for refractive surgery in the aspect of
      minimizing astigmatism after surgery.

PMID- 24893359
TI  - Corneal refractive power and symmetry changes following normalization of ectasias
      treated with partial topography-guided PTK combined with higher-fluence CXL (the
      Athens Protocol).
AB  - PURPOSE: To investigate preoperative and postoperative anterior and posterior
      keratometry and simulated corneal astigmatism in keratoconic eyes treated with
      collagen cross-linking combined with anterior surface normalization by partial
      topography-guided excimer ablation (the Athens Protocol). METHODS: Anterior and
      posterior corneal keratometry were measured by Scheimpflug imaging for 267
      untreated keratoconic eyes. Following treatment, they were assessed 1 year
      postoperatively. RESULTS: Before treatment, average anterior keratometric value
      was 47.06 +/- 6.02 diopters (D) for flat and 51.24 +/- 6.75 D for steep. The
      posterior keratometric values were -6.70 +/- 0.99 D (flat) and -7.67 +/- 1.15 D
      (steep). Anterior astigmatism was on average with-the-rule (-1.97 +/- 6.21 D),
      whereas posterior astigmatism was against-the-rule (+0.53 +/- 1.02 D). The
      posterior and anterior astigmatism were highly correlated (r(2) = 0.839). After
      treatment, anterior keratometric values were 43.97 +/- 5.81 D (flat) and 46.55 +/
      6.82 D (steep). Posterior keratometric values were -6.58 +/- 1.05 D (flat) and 
      7.69 +/- 1.22 D (steep). Anterior astigmatism was on average with-the-rule (-1.56
      +/- 3.80 D), whereas posterior astigmatism was against-the-rule (+0.45 +/- 1.29
      D). The statistically significant (P < .05) keratometric changes indicated
      anterior surface flattening -3.09 +/- 2.67 D (flat) and -4.19 +/- 2.96 D (steep).
      The posterior keratometric changes were not statistically significant (P > .05).
      CONCLUSIONS: Before treatment, there was a strong correlation between posterior
      and anterior corneal astigmatism. After treatment, statistically significant
      anterior keratometric values flattened. The posterior surface keratometric values
      did not demonstrate statistically significant postoperative change: there was
      minimal posterior change, despite the significant anterior surface normalization.

PMID- 24893360
TI  - Corneal epithelial remodeling following cataract surgery: three-dimensional
      investigation with anterior-segment optical coherence tomography.
AB  - PURPOSE: To map corneal and epithelial layer thickness changes following cataract
      removal surgery employing a spectral-domain anterior-segment optical coherence
      tomography system. METHODS: Corneal and epithelial thickness three-dimensional
      profile distribution was clinically imaged preoperatively and up to 3 months
      postoperatively with anterior-segment optical coherence tomography in 116
      consecutive cases. Descriptive statistics investigated central corneal thickness,
      minimum corneal thickness, and epithelial thickness at the central 2-mm area, the
      mean over the 6-mm area, and mid-peripherally at 5-mm ring. RESULTS: In
      comparison to preoperative, the center, mean, and mid-peripheral epithelial
      thickness at the first postoperative day increased by +2.84, +2.35, and +2.25
      MUm, respectively (P < .001, < .001, and = .0014). One week postoperatively, the
      epithelial thickness differences were -1.91, -2.62, and -2.76 MUm, respectively
      (P < .001, < .001, and < .001). Four weeks postoperatively, the differences of 
      0.20, -0.59, and -0.66 MUm for the center, mean, and mid-periphery were not
      statistically significant (P = .6449, .1512, and .11097). Three months
      postoperatively, the differences were -0.05, -0.28, and -0.09 MUm, respectively
      (P = .8722, .2341, and .6431). CONCLUSIONS: Qualitative and quantitative
      assessment of epithelial remodeling following cataract removal indicated that the
      early (1 day and 1 week) corneal and epithelial thickness returned to the
      preoperative baseline 4 weeks postoperatively. This in vivo epithelial and
      corneal screening with optical coherence tomography can be valuable for the
      postoperative assessment and follow-up.

PMID- 24893361
TI  - Dimension reduction for p53 protein recognition by using incremental partial
      least squares.
AB  - As an important tumor suppressor protein, reactivating mutated p53 was found in
      many kinds of human cancers and that restoring active p53 would lead to tumor
      regression. In recent years, more and more data extracted from biophysical
      simulations, which makes the modelling of mutant p53 transcriptional activity
      suffering from the problems of huge amount of instances and high feature
      dimension. Incremental feature extraction is effective to facilitate analysis of
      large-scale data. However, most current incremental feature extraction methods
      are not suitable for processing big data with high feature dimension. Partial
      Least Squares (PLS) has been demonstrated to be an effective dimension reduction
      technique for classification. In this paper, we design a highly efficient and
      powerful algorithm named Incremental Partial Least Squares (IPLS), which conducts
      a two-stage extraction process. In the first stage, the PLS target function is
      adapted to be incremental with updating historical mean to extract the leading
      projection direction. In the last stage, the other projection directions are
      calculated through equivalence between the PLS vectors and the Krylov sequence.
      We compare IPLS with some state-of-the-arts incremental feature extraction
      methods like Incremental Principal Component Analysis, Incremental Maximum Margin
      Criterion and Incremental Inter-class Scatter on real p53 proteins data.
      Empirical results show IPLS performs better than other methods in terms of
      balanced classification accuracy. 

PMID- 24893362
TI  - Genealogical-based method for multiple ontology self-extension in MeSH.
AB  - During the last decade, the advent of Ontologies used for biomedical annotation
      has had a deep impact on life science. MeSH is a well-known Ontology for the
      purpose of indexing journal articles in PubMed, improving literature searching on
      multi-domain topics. Since the explosion of data growth in recent years, there
      are new terms, concepts that weed through the old and bring forth the new.
      Automatically extending sets of existing terms will enable bio-curators to
      systematically improve text-based ontologies level by level. However, most of the
      related techniques which apply symbolic patterns based on a literature corpus
      tend to focus on more general but not specific parts of the ontology. Therefore,
      in this work, we present a novel method for utilizing genealogical information
      from Ontology itself to find suitable siblings for ontology extension. Based on
      the breadth and depth dimensions, the sibling generation stage and pruning
      strategy are proposed in our approach. As a result, on the average, the precision
      of the genealogical-based method achieved 0.5, with the best 0.83 performance of
      category "Organisms." We also achieve average precision 0.69 of 229 new terms in
      MeSH 2013 version. 

PMID- 24893363
TI  - Linking biochemical pathways and networks to adverse drug reactions.
AB  - There is growing interest in investigating the biochemical pathways involved in
      cellular responses to drugs. Here we propose new methods to explore the
      relationships between drugs, biochemical pathways and adverse drug reactions
      (ADRs) at a large scale. Using sparse canonical correlation analysis of 832 drugs
      characterized by 173 pathways and 1385 ADRs profiles, we identified 30 highly
      correlated sets of drugs, pathways and ADRs. This included known and potentially
      novel associations. To evaluate the predictive performance of our method, the
      extracted correlated components were used to predict known ADR profiles from drug
      pathway profiles. A relatively high prediction performance (AUC: 0.894) was
      achieved. To further investigate their association, we developed a network-based
      approach to extracting potentially significant modules of pathway-ADR
      associations. Five statistically significant modules were extracted. We found
      that most of the nodes contained in the modules are either pathways linked to a
      very limited number of drugs or rare ADRs. The work provides a foundation for
      future investigations of ADRs in the context of biochemical pathways under
      different clinical conditions. Our method and resulting datasets will aid in: a)
      the systematic prediction of ADRs, and b) the characterization of novel
      mechanisms of action for existing drugs. This merits additional research to
      further assess its potential in improving personalized drug safety monitoring, as
      well as for the repositioning of drugs in the longer term. 

PMID- 24893364
TI  - Fuzzy preference based feature selection and semisupervised SVM for cancer
      classification.
AB  - DNA microarray data now permit scientists to screen thousand of genes
      simultaneously and determine whether those genes are active or silent in normal
      and cancerous tissues. With the advancement of microarray technology, new
      analytical methods must be developed to find out whether microarray data have
      discriminative signatures of gene expression over normal or cancerous tissues. In
      this paper, we attempt a prediction scheme that combines fuzzy preference based
      rough set (FPRS) method for feature (gene) selection with semisupervised SVMs. To
      show the effectiveness of the proposed approach, we compare the performance of
      this technique with the signal-to-noise ratio (SNR) and consistency based feature
      selection (CBFS) methods. Using six benchmark gene microarray datasets (including
      both binary and multi-class classification problems), we demonstrate
      experimentally that our proposed scheme can achieve significant empirical success
      and is biologically relevant for cancer diagnosis and drug discovery. 

PMID- 24893365
TI  - Effect of statistically derived fiber models on the estimation of cardiac
      electrical activation.
AB  - Myocardial fiber orientation plays a critical role in the electrical activation
      and subsequent contraction of the heart. To increase the clinical potential of
      electrophysiological (EP) simulation for the study of cardiac phenomena and the
      planning of interventions, accurate personalization of the fibers is a necessary
      yet challenging task. Due to the difficulties associated with the in vivo imaging
      of cardiac fiber structure, researchers have developed alternative techniques to
      personalize fibers. Thus far, cardiac simulation was performed mainly based on
      rule-based fiber models. More recently, there has been a significant interest in
      data-driven and statistically derived fiber models. In particular, our predictive
      method in [1] allows us to estimate the unknown subject-specific fiber
      orientation based on the more easily available shape information. The aim of this
      work is to estimate the effect of using such statistical predictive models for
      the estimation of cardiac electrical activation times and patterns. To this end,
      we perform EP simulations based on a database of ten canine ex vivo diffusion
      tensor imaging (DTI) datasets that include normal and failing cases. To assess
      the strength of the fiber models under varying conditions, we consider both sinus
      rhythm and biventricular pacing simulations. The results show that 1) the
      statistically derived fibers improve the estimation of the local activation times
      by an average of 53.7% over traditional rule-based models, and that 2) the
      obtained electrical activations are consistently similar to those of the DTI
      based fibers. 

PMID- 24893366
TI  - The effects of HCN and KLT ion channels on adaptation and refractoriness in a
      stochastic auditory nerve model.
AB  - An accurate model of auditory nerve fibers (ANFs) may assist in developing
      improved cochlear implant (CI) stimulation strategies. Previous studies have
      shown that the original Hodgkin-Huxley (HH) model may be better at describing
      nodes of Ranvier in ANFs than models for other mammalian axon types. However, the
      HH model is still unable to explain a number of phenomena observed in auditory
      nerve responses to CI stimulation such as adaptation to high-rate stimulation and
      the time course of relative refractoriness. Recent physiological investigations
      of ANFs have shown the presence of a number of ion channel types not considered
      in the previous modeling studies, including low-threshold potassium (KLT)
      channels and hyperpolarization-activated cation (HCN) channels. In this paper, we
      investigate inclusion of these ion channel types in a stochastic HH model of a
      single node of Ranvier. Simulation results for pulse trains with rates of 200,
      800, and 2000 pulse/s suggests that both the KLT channels and HCN channels can
      produce adaptation in the spike rate. However, the adaptation due to KLT is
      restricted to higher stimulation rates, whereas the adaptation due to HCN is
      observed across all stimulation rates. Additionally, using pulse pairs it was
      found that KLT increased both the absolute and the relative refractory periods.
      HCN on its own increased just the relative refractory period, but produced a
      synergistic increase in the absolute refractory period when combined with KLT.
      Together these results argue strongly for the need to consider HCN and KLT
      channels when studying CI stimulation of ANFs. 

PMID- 24893368
TI  - Learning-based hierarchical graph for unsupervised matting and foreground
      estimation.
AB  - Automatically extracting foreground objects from a natural image remains a
      challenging task. This paper presents a learning-based hierarchical graph for
      unsupervised matting. The proposed hierarchical framework progressively condenses
      image data from pixels into cells, from cells into components, and finally from
      components into matting layers. First, in the proposed framework, a graph-based
      contraction process is proposed to condense image pixels into cells in order to
      reduce the computational loads in the subsequent processes. Cells are further
      mapped into matting components using spectral clustering over a learning based
      graph. The graph affinity is efficiently learnt from image patches of different
      resolutions and the inclusion of multiscale information can effectively improve
      the performance of spectral clustering. In the final stage of the hierarchical
      scheme, we propose a multilayer foreground estimation process to assemble matting
      components into a set of matting layers. Unlike conventional approaches, which
      typically address binary foreground/background partitioning, the proposed method
      provides a set of multilayer interpretations for unsupervised matting.
      Experimental results show that the proposed approach can generate more consistent
      and accurate results as compared with state-of-the-art techniques. 

PMID- 24893367
TI  - Learning to rank atlases for multiple-atlas segmentation.
AB  - Recently, multiple-atlas segmentation (MAS) has achieved a great success in the
      medical imaging area. The key assumption is that multiple atlases have greater
      chances of correctly labeling a target image than a single atlas. However, the
      problem of atlas selection still remains unexplored. Traditionally, image
      similarity is used to select a set of atlases. Unfortunately, this heuristic
      criterion is not necessarily related to the final segmentation performance. To
      solve this seemingly simple but critical problem, we propose a learning-based
      atlas selection method to pick up the best atlases that would lead to a more
      accurate segmentation. Our main idea is to learn the relationship between the
      pairwise appearance of observed instances (i.e., a pair of atlas and target
      images) and their final labeling performance (e.g., using the Dice ratio). In
      this way, we select the best atlases based on their expected labeling accuracy.
      Our atlas selection method is general enough to be integrated with any existing
      MAS method. We show the advantages of our atlas selection method in an extensive
      experimental evaluation in the ADNI, SATA, IXI, and LONI LPBA40 datasets. As
      shown in the experiments, our method can boost the performance of three widely
      used MAS methods, outperforming other learning-based and image-similarity-based
      atlas selection methods. 

PMID- 24893369
TI  - An optically powered CMOS tracking system for 3 T magnetic resonance environment.
AB  - In this work, a fully optical Complementary Metal Oxide Semiconductor (CMOS)
      based catheter tracking system designed for 3 T Magnetic Resonance Imaging (MRI)
      environment is presented. The system aims to solve the Radio Frequency (RF)
      induced heating problem present in conventional wired catheter tracking systems
      used in MRI. It is based on an integrated circuit, consisting of a receiver and
      an optical power supply unit. The optical power supply unit includes a single on
      chip photodiode and a DC-DC converter that boosts the low photodiode voltage
      output to voltages greater than 1.5 V. Through an optically driven switch, the
      accumulated charge on an a storage capacitor is transferred to the rest of the
      system. This operation is novel in the way that it is fully optical and the
      switch control is done through modulation of the applied light. An on-chip local
      oscillator signal for the receiver is avoided by application of an RF signal that
      is generated by the MRI machine at the receiving period. The signals received by
      a micro-coil antenna are processed by the on-chip direct conversion receiver. The
      processed signal is then transferred, also optically, to the outside world for
      tracking purposes. The frequency encoding method is used for MRI tracking.
      Operation with various levels of external optical power does not generate
      noticeble temperature increase in the system. The overall system is successfully
      tested in a 3 T MRI machine to demonstrate its full operation. 

PMID- 24893370
TI  - A study on quality assessment for medical ultrasound video compressed via HEVC.
AB  - The quality of experience and quality of service provided in the healthcare
      sector are critical in evaluating the reliable delivery of the healthcare
      services provided. Medical images and videos play a major role in modern e-health
      services and have become an integral part of medical data communication systems.
      The quality evaluation of medical images and videos is an essential process, and
      one of the ways of addressing it is via the use of quality metrics. In this
      paper, we evaluate the performance of seven state-of-the-art video quality
      metrics with respect to compressed medical ultrasound video sequences. We study
      the performance of each video quality metric in representing the diagnostic
      quality of the video, by evaluating the correlation of each metric with the
      subjective opinions of medical experts. The results indicate that the visual
      information fidelity, structural similarity index, and universal quality index
      metrics show good correlation with the subjective scores provided by medical
      experts. The tests also investigate the performance of the emerging video
      compression standard, high-efficiency video coding-HEVC, for medical ultrasound
      video compression. The results show that, using HEVC with the considered
      ultrasound video sequences, a diagnostically reliable compressed ultrasound video
      can be obtained for compression with values of the quantization parameter up to
      35. 

PMID- 24893371
TI  - EEG activity during movement planning encodes upcoming peak speed and
      acceleration and improves the accuracy in predicting hand kinematics.
AB  - The relationship between movement kinematics and human brain activity is an
      important and fundamental question for the development of neural prosthesis. The
      peak velocity and the peak acceleration could best reflect the feedforward-type
      movement; thus, it is worthwhile to investigate them further. Most related
      studies focused on the correlation between kinematics and brain activity during
      the movement execution or imagery. However, human movement is the result of the
      motor planning phase as well as the execution phase and researchers have
      demonstrated that statistical correlations exist between EEG activity during the
      motor planning and the peak velocity and the peak acceleration using grand
      average analysis. In this paper, we examined whether the correlations were
      concealed in trial-to-trial decoding from the low signal-to-noise ratio of EEG
      activity. The alpha and beta powers from the movement planning phase were
      combined with the alpha and beta powers from the movement execution phase to
      predict the peak tangential speed and acceleration. The results showed that EEG
      activity from the motor planning phase could also predict the peak speed and the
      peak acceleration with a reasonable accuracy. Furthermore, the decoding accuracy
      of the peak speed and the peak acceleration could both be improved by combining
      band powers from the motor planning phase with the band powers from the movement
      execution.

PMID- 24893372
TI  - FN-DFE: fuzzy-neural data fusion engine for enhanced resilient state-awareness of
      hybrid energy systems.
AB  - Resiliency and improved state-awareness of modern critical infrastructures, such
      as energy production and industrial systems, is becoming increasingly important.
      As control systems become increasingly complex, the number of inputs and outputs
      increase. Therefore, in order to maintain sufficient levels of state-awareness, a
      robust system state monitoring must be implemented that correctly identifies
      system behavior even when one or more sensors are faulty. Furthermore, as
      intelligent cyber adversaries become more capable, incorrect values may be fed to
      the operators. To address these needs, this paper proposes a fuzzy-neural data
      fusion engine (FN-DFE) for resilient state-awareness of control systems. The
      designed FN-DFE is composed of a three-layered system consisting of: 1)
      traditional threshold based alarms; 2) anomalous behavior detector using self
      organizing fuzzy logic system; and 3) artificial neural network-based system
      modeling and prediction. The improved control system state-awareness is achieved
      via fusing input data from multiple sources and combining them into robust
      anomaly indicators. In addition, the neural network-based signal predictions are
      used to augment the resiliency of the system and provide coherent state-awareness
      despite temporary unavailability of sensory data. The proposed system was
      integrated and tested with a model of the Idaho National Laboratory's hybrid
      energy system facility known as HYTEST. Experiment results demonstrate that the
      proposed FN-DFE provides timely plant performance monitoring and anomaly
      detection capabilities. It was shown that the system is capable of identifying
      intrusive behavior significantly earlier than conventional threshold-based alarm
      systems. 

PMID- 24893377
TI  - Effect of beverage flavor on body hydration in Hong Kong Chinese children
      exercising in a hot environment.
AB  - The purpose of the current study was to examine the effect of flavor on voluntary
      drinking and thermoregulatory responses in Chinese boys and girls exercising
      intermittently in a hot environment. Fourteen boys and girls (9 to 11 years old)
      performed four 3-hour intermittent exercise sessions (20-min walking sessions at
      50% VO2peak followed by a 25-minute rest period) in a hot and humid environment
      (~30  degrees C ambient temperature and ~70% relative humidity). The participants
      consumed 1 of 4 beverages ad libitum in a randomized sequence by using a Latin
      square principle: unflavored water (W), orange-flavored water (OF), lemon
      flavored water (LF), and grape-flavored water (GF). No differences were observed
      in the total fluid intake (W vs. OF vs. LF vs. GF: Boys, 441 +/- 114 vs. 493 +/-
      106 vs. 387 +/- 83 vs. 568 +/- 146 ml; Girls, 613 +/- 131 vs. 923 +/- 204 vs. 825
      +/- 157 vs. 790 +/- 166 ml), urine and sweat output, and physiological perceptual
      variables among trials and between sexes. The results suggested that Chinese
      children can maintain body fluid balance while exercising moderately in a hot and
      humid environment by ad libitum drinking. The flavor of the beverages had no
      impact on the voluntary drinking and the state of hydration in the current study.

PMID- 24893379
TI  - Two protocols to measure mitochondrial capacity in women and adolescent girls: a
      31P-MRS preliminary study.
AB  - The phosphocreatine (PCr) recovery time constant (tau) following exercise
      provides a measure of mitochondrial oxidative capacity. The purpose of this
      investigation was to use 2 different protocols to determine tau in adolescent
      females. 31P-MR spectra were collected during 2 exercise tests in 6 adolescent
      girls (13.8 +/- 0.3 y) and 7 women (23.2 +/- 3.4 y). The first test consisted of
      23 repeated 4 seconds maximal isometric calf contractions separated by 12-second
      recovery; PCr recovery between the final 18 contractions was used to calculate
      tau. The second test was a sustained 20-second maximal contraction; recovery was
      fitted with an exponential function to measure tau. PCr tau did not significantly
      differ between groups: (gated exercise: 4 girls: 16 +/- 5 s, 7 women: 17 +/- 5 s,
      p; sustained exercise: 6 girls: 19 +/- 6 s, 7 women: 19 +/- 4 s). Bland-Altman
      analysis demonstrated a close agreement between sustained and gated exercise.
      Both gated and sustained exercise appear feasible in a pediatric population, and
      offer a noninvasive evaluation of mitochondrial oxidative capacity. 

PMID- 24893380
TI  - Conservative values.

PMID- 24893381
TI  - Debate lingers over role of lasers in periodontal therapy.

PMID- 24893382
TI  - An analytical approach to improving practice performance.

PMID- 24893383
TI  - DenMat' new Splash!(r)Max VPS impression material: premium quality at an
      affordable price.

PMID- 24893384
TI  - DENTSPLY Caulk' Cordless Impression System: a procedural change for the better.

PMID- 24893385
TI  - Heraeus Kulzer, Dental Wings collaboration helping bring digital impressions to
      the masses.

PMID- 24893386
TI  - Kettenbach: Striving to accommodate dentists'clinical preferences in
      impressioning.

PMID- 24893387
TI  - Response.

PMID- 24893388
TI  - Planmeca' modular PlanScanTM offers the ultimate in scanning flexibility.

PMID- 24893389
TI  - Home birth.

PMID- 24893390
TI  - NMC issues Facebook warning to midwives.

PMID- 24893391
TI  - Pregnancy drinking study could send out wrong message.

PMID- 24893392
TI  - Keep up the pressure to save lives.

PMID- 24893394
TI  - Returning to practice: a personal vision.

PMID- 24893393
TI  - Fire in her belly.

PMID- 24893396
TI  - How to ... teach a mother the technique of hand expressing.

PMID- 24893395
TI  - Maternal and neonatal outcomes among obese women.

PMID- 24893397
TI  - Leadership ... it starts with you.

PMID- 24893398
TI  - Should you be the next RCM president?

PMID- 24893399
TI  - A new vision for health visiting.

PMID- 24893400
TI  - Cracking GDM controversy.

PMID- 24893401
TI  - Fighting for survival.

PMID- 24893403
TI  - Maternity reacts.

PMID- 24893402
TI  - Picking and choosing.

PMID- 24893404
TI  - Our breast efforts.

PMID- 24893405
TI  - Getting it right from the start.

PMID- 24893406
TI  - It's all in the eye.

PMID- 24893407
TI  - A day in the life of ... a third-year student midwife.

PMID- 24893409
TI  - Reducing CS rates at UCLH.

PMID- 24893408
TI  - Flu vaccine--a must for all midwives.

PMID- 24893410
TI  - Response to acupuncture in the treatment of hyperemesis gravidarum.

PMID- 24893411
TI  - Are healthy women to be offered c-sections?

PMID- 24893412
TI  - New pensions offer is on the table and set to be examined.

PMID- 24893413
TI  - Mobile midwifery in Ghana.

PMID- 24893414
TI  - Blue days for the NHS.

PMID- 24893415
TI  - Mind over matter: minimising pain in labour.

PMID- 24893416
TI  - How to ... perform an examination of the placenta.

PMID- 24893417
TI  - The use of video during birth.

PMID- 24893418
TI  - A call for a Day of Action.

PMID- 24893419
TI  - The RCM's new ePortfolio for members.

PMID- 24893420
TI  - Dying for a cigarette.

PMID- 24893423
TI  - Filling the knowledge gap.

PMID- 24893421
TI  - Promoting lifelong learning.

PMID- 24893422
TI  - Effectively realising change.

PMID- 24893424
TI  - 75 years of maternity care.

PMID- 24893425
TI  - The big bump gets its message across.

PMID- 24893426
TI  - An elusive ideal.

PMID- 24893427
TI  - A day in the life of ... a consultant midwife for infant feeding.

PMID- 24893428
TI  - Are you missing out on payments for copying of articles/book extracts?

PMID- 24893430
TI  - Community midwives on-call.

PMID- 24893429
TI  - Acupuncture in the treatment of hyperemesis gravidarum.

PMID- 24893431
TI  - Ban on telling parents the sex of their child?

PMID- 24893432
TI  - RCM and unions slam health reforms passed in Commons.

PMID- 24893433
TI  - Delivering a hands-on approach.

PMID- 24893434
TI  - Delivering chart success.

PMID- 24893435
TI  - Ignorance is bliss?

PMID- 24893437
TI  - How to ... prepare powdered infant formula.

PMID- 24893436
TI  - Maternal sleep practices and still birth risk.

PMID- 24893438
TI  - Valued support.

PMID- 24893439
TI  - The maternity maze.

PMID- 24893440
TI  - Tread carefully.

PMID- 24893441
TI  - Flu jab? There's no excuse not to.

PMID- 24893442
TI  - Culture shift.

PMID- 24893443
TI  - Helping the hardest to rearch.

PMID- 24893444
TI  - Financial pain relief.

PMID- 24893445
TI  - Speaking from experience.

PMID- 24893446
TI  - A day in the life of ... a smoking in pregnancy specialist.

PMID- 24893447
TI  - [Photon counting CT].
AB  - Photon counting CT is a new technology that enables us to improve the quality of
      images by a conventional CT, in which the detection of transmitted photons is
      conducted by an integration of photon energies. This paper describes the features
      and advantages of the photon counting detection compared to the energy
      integration detection. They are (1) reduction of electrical noise and improvement
      of the signal-to-noise ratio, (2) improvement of the image contrast using the
      weighting factors to images acquired with energy bins, (3) k-edge imaging by
      setting two energy bins at the k-edge of some contrast media such as gadopenteto
      megruminacid and gold-nanoparticles, and (4) material decomposition using the
      data acquired with multiple energy windows. For the material decomposition, the
      principal component analysis, singular value decomposition method, and the
      application of the artificial neural network are described. The photon counting
      CT technique has a potential to improve the diagnostic accuracy and introduce new
      clinical methods, however, much efforts are required to use this technology in
      the clinical situation.

PMID- 24893449
TI  - [New technology in radiotherapy treatment planning].
AB  - Four-dimensional radiation therapy (4DRT) and adaptive radiation therapy (ART)
      are treatments to account for respiratory motion and anatomical changes during a
      course of treatment, respectively. Recent development of both imaging and
      delivery techniques made these radiation therapy possible. In these planning,
      dose distributions are calculated with multiple image sets for example each
      respiratory phase constituting 4-dimensional computed tomography and cone-beam
      computed tomography acquired on each treatment day. To evaluate overall dose
      distributions, we need to accumulate dose distributions calculated with multiple
      image sets. However, pixel-wise dose accumulation is impossible because it does
      not accumulate dose based on anatomy if image sets are different. Deformable
      image registration (DIR) is used to find corresponding anatomical points between
      image sets. Thus, dose accumulation based on DIR is a promising technology to
      enable us to evaluate overall dose distributions of 4DRT and ART. In this
      article, I will briefly introduce dose accumulation based on DIR and its
      application to 4DRT and ART.

PMID- 24893448
TI  - [Innovation and the next generation radiotherapy system].
AB  - Innovation is the key to future success for Japan that is slowly falling behind.
      Industries targeted by the "Abenomics" growth strategy include healthcare and
      medicine. Since cancer is the leading cause of death in Japan, the development of
      a system that can detect and treat early stage cancers will be very valuable for
      patient QOL and reducing health care costs. Although the effectiveness of
      radiation therapy for treating early stage cancer is widely recognized, there has
      been no system to treat small, moving tumors with sub millimeter accuracy. A
      project supported by NEDO develops a "Next-Generation Radiation Therapy System"
      that uses high energy, narrow X-rays beams that can be accurately pinpointed deep
      inside the body. Performance testing of a prototype system is currently underway
      at the National Center for Global Health and Medicine in Tokyo.

PMID- 24893450
TI  - [Development of transXend detector and its application to low dose exposure CT].
AB  - For practical energy-resolved computed tomography (CT), a transXend detector is
      proposed. The transXend detector consists of several segment detectors which are
      aligned along the direction of X-ray incidence. With response functions of
      segment detectors, the energy distribution of incident X-rays is obtained after
      unfolding process. Because the transXend detector measures X-rays as electric
      currents, it has no limit of counting rate: the number of X-rays in medical
      diagnosis ranges 10(6)-10(9)n/mm2/s, measuring energy of each X-ray is not
      practical at this stage. The operation principle and ways of application of the
      transXend detector are described. With defining narrow energy ranges in an
      unfolding process, effective atomic numbers are estimated with using white X
      rays: the transXend detector can cut out quasi-monochromatic X-rays out of white
      X-rays. With the transXend detector with absorbers among the segment detectors,
      the directions of material thickness increment are shown different in the graph
      made of electric current ratios measured by the segment detectors. Using the
      current ratio graph, the thicknesses of the materials along the line X-rays
      passed are estimated. In other words, cancers marked by contrast agent can be
      detected with one transmission measurement, and possibly are measured and
      positioned by transmission measurements from two directions.

PMID- 24893452
TI  - [Basics of medical particle accelerators--cyclotrons].

PMID- 24893451
TI  - [Thermoluminescence Slab Dosimeter].
AB  - In 1953 F. Daniels et al. used the property of thermoluminescence in dosimetry
      for the first time. Since then, numerous TLD have been developed. 2D TLD was
      investigated for the first time in 1972 by P Broadhead. However, due to excessive
      fading, difficulties with handling and the time required for measurements,
      development stalled. At the current time, the majority of TLD are used in small
      scale, localized dosimetry with a wide dynamic range and personal dosimeters for
      exposure management. Urushiyama et. al. have taken advantage of the
      commoditization of CCD cameras in recent years--making large area, high
      resolution imaging easier--to introduce and develop a 2D TLD. It is expected that
      these developments will give rise to a new generation of applications for 2D TL
      dosimetry. This paper introduces the "TL Slab Dosimeter" developed jointly by
      Urushiyama et. al. and our team, its measurement system and several typical usage
      scenarios.

PMID- 24893453
TI  - We're all in this together.

PMID- 24893454
TI  - How to... clarification.

PMID- 24893455
TI  - Put midwives at the heart of commissioning.

PMID- 24893456
TI  - Study: two glasses of wine could put unborn baby at risk.

PMID- 24893457
TI  - Delaying the inevitable.

PMID- 24893458
TI  - Celebrating excellence in midwifery.

PMID- 24893459
TI  - Primes numbers.

PMID- 24893460
TI  - Second time around.

PMID- 24893461
TI  - Folic acid use in preventing neural tube defects.

PMID- 24893462
TI  - How to ... perform a vaginal examination.

PMID- 24893463
TI  - On your screen and in your pocket!

PMID- 24893465
TI  - A first-class production.

PMID- 24893464
TI  - Goodbye 'to the golden years' of retirement.

PMID- 24893467
TI  - When things get personal....

PMID- 24893466
TI  - Breaking through the barriers.

PMID- 24893468
TI  - 12 bumps are better than one....

PMID- 24893469
TI  - A critical approach.

PMID- 24893471
TI  - Leading the way.

PMID- 24893470
TI  - Task force.

PMID- 24893472
TI  - A day in the life of ... a community midwife.

PMID- 24893473
TI  - Breastfeeding is off the agenda.

PMID- 24893475
TI  - A call for anyone who knew Olive/Margaret to get in contact.

PMID- 24893476
TI  - NICE ready to revise its c-section guidelines.

PMID- 24893474
TI  - The role of the practice educator.

PMID- 24893477
TI  - When is it safe to fly? Pregnant women want better advice.

PMID- 24893478
TI  - A test of temperament.

PMID- 24893480
TI  - The way we were.

PMID- 24893479
TI  - Like-minded fellow.

PMID- 24893481
TI  - Breastfeeding and child behaviour at five years.

PMID- 24893482
TI  - How to ... help with positioning and attachment.

PMID- 24893483
TI  - Working together.

PMID- 24893484
TI  - What is Barth syndrome?

PMID- 24893485
TI  - 'My mother-in-law tells me what to do'.

PMID- 24893487
TI  - Reaching out to the young.

PMID- 24893486
TI  - Prevention is the best cure.

PMID- 24893488
TI  - Learning and skills counsel.

PMID- 24893489
TI  - Doing what's best for baby.

PMID- 24893490
TI  - A day in the life of ... an infant-feeding specialist midwife.

PMID- 24893491
TI  - [Experience using the isocenter verification device in proton therapy equipment].
AB  - In this study, we developed an isocenter verification device for use in proton
      therapy. Radiation and mechanical isocenters were verified for treatment
      equipment including room lasers, a digital radiography system and the beam axis
      of a rotational gantry. The special feature of this device is its ability to
      correlate the position of the three isocenters in one measurement and thus
      improve accuracy compared to the conventional method using three separate
      devices. The reproducibility of the method and the fluctuation of the position of
      the beam axis isocenter were both investigated using this device for almost a
      year. Monthly measurements of the isocenter position were acquired for two
      gantries and it was found that the fluctuation was +/- 0.10mm for the up-to-down
      direction and +/- 0.16mm for the right-to-left direction in Gantry 1 and was +/
      0.14mm for the up-to-down direction and +/-0.18mm for the right-to-left direction
      in Gantry 2. We could be measured with a repeatability of +/-0.18 mm or less by
      using developed device for the relative positional relationship between each
      isocenters. Because we can confirm results in approximately 30 minutes, we can
      perform a quality control after a clinical practice.

PMID- 24893492
TI  - [Outline of standard dosimetry of absorbed dose to water in external beam
      radiotherapy].
AB  - In this report, history of the dose standard system, calibration of ionization
      chamber and standard dosimetry protocol to assure dose traceability was
      interpreted. The water absorbed dose standard is newly established in Japan and
      calibration service and dosimetry protocol based on the water absorbed dose has
      been provided. A lot of uncertainties exist in current complicated radiation
      therapy. However, uncertainty of dose delivery will be reduced and further
      progress of quality assurance is expected by shift to the absorbed dose
      calibration system in radiation therapy field.

PMID- 24893493
TI  - [National primary standard of absorbed dose rate to water using a graphite
      calorimeter].
AB  - The calibration service in terms of absorbed dose to water started from 2011
      after establishment of the national primary standard using a graphite calorimeter
      at the national metrology institute of Japan (NMIJ) and JCSS accreditation of the
      association for nuclear technology in medicine (ANTM). Accordingly, a new
      dosimetry protocol was introduced as JSMP12, in which details of the national
      standard were also described. This report presents a short review of the
      standard, a key comparison result, and a comparison result of calibration
      coefficients by JSMP01 and JSMP12.

PMID- 24893494
TI  - [Beam quality conversion factor].
AB  - This report describes the update of the beam quality conversion factor k(Q,Q0) of
      the standard dosimetry protocol in Japan. The k(Q,Q0) corrects for the difference
      between the response of an ionization chamber in the reference beam quality Q0
      used for calibrating the chamber and in the actual user beam quality Q. All
      changes of k(Q,Q0) were caused by the perturbation correction factors which were
      recalculated by Monte Carlo simulation. With a calculation process, unsolved
      problems in this update are also discussed here.

PMID- 24893496
TI  - Progress towards the millennium development goals in SA.

PMID- 24893495
TI  - [Image property and technological development in CT-System].

PMID- 24893497
TI  - Successfully controlling malaria in South Africa.
AB  - Following major successes in malaria control over the past 75 years, South Africa
      is now embarking on a malaria elimination campaign with the goal of zero local
      transmission by the year 2018. The key control elements have been intensive
      vector control, primarily through indoor residual spraying, case management based
      on parasitological diagnosis using evidence-based drug policies with artemisinin
      based combination therapy since 2001, active health promotion in partnership with
      communities living in the malaria transmission areas, and cross-border
      collaborations. Political commitment and long-term funding for the malaria
      control programme have been a critical component of the programme's success.
      Breaking the cycle of transmission through strengthening of active surveillance
      using sensitive molecular tests and field treatment of asymptomatic persons,
      monitoring for antimalarial drug resistance and insecticide resistance,
      strengthening cross-border initiatives, and ongoing programme advocacy in the
      face of a significant decrease in disease burden are key priorities for achieving
      the elimination goal.

PMID- 24893498
TI  - Effectiveness of pneumococcal conjugate vaccine and rotavirus vaccine
      introduction into the South African public immunisation programme.
AB  - Immunisation has contributed greatly to the control of vaccine-preventable
      diseases and therefore to improvements in health and survival, especially among
      young children, and remains one of the most successful and cost-effective public
      health interventions. This remains true for many of the newer, more expensive
      vaccines. Vaccines against invasive pneumococcal disease and rotavirus infection
      were introduced into the South African Expanded Programme on Immunization in
      April 2009. This article describes the rationale for and process of the
      introduction of these two vaccines, pneumococcal conjugate vaccine and rotavirus
      vaccine. It also aims to evaluate the success of and challenges related to their
      introduction, in terms of both achieving universal coverage and improving
      survival and health in South African children.

PMID- 24893499
TI  - Laboratory information system data demonstrate successful implementation of the
      prevention of mother-to-child transmission programme in South Africa.
AB  - BACKGROUND: Monitoring the prevention of mother-to-child transmission (PMTCT)
      programme to identify gaps for early intervention is essential as South Africa
      progresses from prevention to elimination of HIV infection in children. Early
      infant diagnosis (EID) by an HIV polymerase chain reaction (PCR) test is
      recommended at 6 weeks of age for all HIV-exposed infants. The National Health
      Laboratory Service (NHLS) performs the PCR tests for the public health sector and
      stores test data in a corporate data warehouse (CDW). OBJECTIVES: To demonstrate
      the utility of laboratory data for monitoring trends in EID coverage and early
      vertical transmission rates and to describe the scale-up of the EID component of
      the PMTCT programme. METHODS: HIV PCR test data from 2003 to 2012 inclusive were
      extracted from the NHLS CDW by year, province, age of infant tested and test
      result and used to calculate EID coverage and early vertical transmission rates
      to provincial level. RESULTS: Rapid scale-up of EID over the first decade of the
      PMTCT programme was evident from the 100-fold increase in PCR tests to 350 000 by
      2012. In 2012, 73% of the estimated 270 000 HIV-exposed infants requiring an
      early PCR were tested and the early vertical transmission rate had fallen to 2.4%
      as a result of successful implementation of the PMTCT programme. CONCLUSIONS:
      Laboratory data can provide real time, affordable monitoring of aspects of the
      PMTCT programme and assist in achieving virtual elimination of paediatric HIV
      infection in South Africa.

PMID- 24893500
TI  - Elimination of mother-to-child transmission of HIV in South Africa: rapid scale
      up using quality improvement.
AB  - BACKGROUND: South Africa (SA) is committed to achieving the goal of eliminating
      mother-to-child transmission (MTCT) of HIV by 2015. To achieve this, universal
      coverage of quality antenatal, labour, delivery and postnatal services for all
      women has to be attained. Over the past decade, the prevention of mother-to-child
      transmission (PMTCT) programme has been scaled up to reach all healthcare
      facilities in the country. However, challenges persist in achieving 100% coverage
      and access to the programme. OBJECTIVES: We describe the process undertaken by
      the National Department of Health (NDoH), in collaboration with partners, to
      develop, implement and monitor a data-driven intervention to improve facility,
      district, provincial and national PMTCT-related performance. METHODS: Between
      2011 and 2013, the NDoH developed and implemented an intervention using data
      driven participatory processes to understand facility-level bottlenecks to
      optimise PMTCT implementation and to scale up priority PMTCT actions nationally.
      RESULTS: There was remarkable improvement across all key indicators in the PMTCT
      cascade over the 3 years 2011-2013. Simple monitoring tools such as a visual
      dashboard and data for action reports were successfully used to improve the
      performance of the PMTCT programme across SA. MTCT has shown a significant
      downward trend. CONCLUSIONS: It is feasible to implement district-level, data
      driven quality improvement processes at a national scale to improve the
      performance of the PMTCT programme at the local level.

PMID- 24893501
TI  - Tuberculosis control in South Africa: successes, challenges and recommendations.
AB  - Tuberculosis (TB) remains a global health threat, and South Africa (SA) has one
      of the world's worst TB epidemics driven by HIV. Among the 22 countries with the
      highest burden of TB, SA has the highest estimated incidence and prevalence of
      TB, the second highest number of diagnosed multidrug-resistant TB cases, and the
      largest number of HIV-associated TB cases. Although SA has made notable progress
      in reducing TB prevalence and deaths and improving treatment outcomes for new
      smear-positive TB cases, the burden of TB remains enormous. SA has the means to
      overcome this situation. In addition to better implementing the basics of TB
      diagnosis and treatment, scaling up the use of Xpert MTB/RIF as a replacement for
      sputum smear microscopy, strengthening case finding in and beyond healthcare
      facilities and a greater focus on TB prevention for people living with HIV,
      particularly earlier initiation of and scaling up antiretroviral therapy and
      scaling up continuous isoniazid preventive therapy, will have a substantial
      impact on TB control. New TB drugs, diagnostics and vaccines are required to
      further accelerate progress towards improved TB control in SA and beyond.

PMID- 24893502
TI  - A brief history of South Africa's response to AIDS.
AB  - The story of the AIDS response in South Africa over the past 4 years is one of
      great progress after almost a decade of complex and tragic denialism that united
      the world and civil society in a way not seen since the opposition to apartheid.
      Today the country can boast > 2 million people on antiretroviral therapy, far and
      away the largest number in the world. Prevention efforts appear to be yielding
      results. The estimated number of annual new HIV infections declined by 79 000
      between 2011 and 2012. New HIV infections among adults aged 15-49 years are
      projected to decline by 48% by 2016, from 414,000 (2010) to -215,000 (2016). The
      national incidence rate has reached its lowest level since the disease was first
      declared an epidemic in 1992, translating into reductions in both infant and
      under-5 mortality and an increase in life expectancy from 56 to 60 years over the
      period 2009-2011 alone. This is largely thanks to a civil society movement that
      was prepared to pose a rights-based challenge to a governing party in denial, and
      to brave health officials, politicians and clinicians working in a hostile system
      to bring about change.

PMID- 24893503
TI  - [Squamous cell carcinoma of the esophagus].

PMID- 24893504
TI  - [Adenocarcinoma of the esophagus and the gastroesophageal junction].

PMID- 24893505
TI  - [Epidemiology and pathogenesis of gastric cancer].

PMID- 24893506
TI  - [Stomach cancer. Morphology].

PMID- 24893507
TI  - [Neuroendocrine neoplasms of the stomach].

PMID- 24893508
TI  - [Gastrointestinal stromal tumors].

PMID- 24893509
TI  - [Molecular-clinical issues of gastrointestinal stromal tumors].

PMID- 24893510
TI  - [European healthcare].

PMID- 24893511
TI  - [Teenagers' representations of food in the Pays de la Loire].
AB  - CONTEXT: The National Nutrition Health Study showed that the objectives of the
      National Nutrition Health Programme, launched in 2001 to promote the health of
      all French people, had not been achieved, especially in the adolescent
      population. The objective of this study was to identify teenagers'
      representations regarding food. It was carried out in order to more effectively
      tailor prevention messages to this particular population, which is particularly
      concerned by the "nutritional risk". METHODS: Qualitative investigations by semi
      directive interviews with 46 teenage volunteers,from 5 high schools in 2
      departments in the west of France. A content analysis was conducted inductively
      after full transcript of the interviews. RESULTS: The study showed that nutrition
      was a means of autonomy and emancipation from the parental influence. Teenagers
      were suspicious and anxious about the health risks associated with processed
      food. Fast food restaurants were a "place for teenagers" synonymous with pleasure
      and freedom. They valued "organic" and "homemade" foods. The sexual
      representations of food consisted of a "slim" image for girls and a "virile"
      image for boys. A close relationship between food and living beings was
      responsible for refusal of certain types of food. Although prevention messages
      were integrated in various ways, they were effectively recalled by teenagers.
      CONCLUSION: The nutritional representations of teenagers are poorly known and
      sometimes contrary to commonly health beliefs and must be taken into account when
      preparing nutrition prevention programmes.

PMID- 24893512
TI  - [Restoring the complexity of reality in theoretical health promotion approaches
      through incorporating the identity of the subject].
AB  - The theoretical frameworks presently dominating health promotion practices mainly
      focus on the individual's psychosocial and cognitive components. When focusing on
      environments, these frameworks barely relate contextual elements to the
      individuals who give them a real existence. Because of the disjunction and
      reduction they create, the main theoretical readings only partially recognize the
      complexity of social life and therefore lose the Subject. Lacking theoretical
      reliance, these readings fail to meet the Ottawa Charter principles. Based on
      critical analysis of the main theoretical frameworks, we discuss the influence of
      disciplinary backgrounds on our modes of knowledge, tackling how epidemiological
      and behavioral thinking affect how we understand, conceive and problematize the
      objects in these fields. Based on this analysis, we illustrate how these
      epistemologies oversimplify social realities related to health. In order to
      encounter the lost subject of health promotion and thereby achieve Ottawa
      Charter's principles, we propose an innovative theoretical approach based on
      Schutz' socio-phenomenological thinking and Morin's complexity paradigm. Our
      theoretical proposal aims to recognize and reconcile significant aspects of
      individuals' meaningful life experiences, while integrating common sense
      principles. By transiting through the subject's identity, this theoretical
      proposal tends to unify all meaningful aspects that subtend social life at the
      subject's scale.

PMID- 24893513
TI  - [Difficulties of a longitudinal epidemiological follow-up study in French
      occupational medicine].
AB  - INTRODUCTION: This study was designed to describe the difficulties of
      epidemiological follow-up of employees by occupational health services. METHODS:
      This study was based on two transverse studies conducted by the Pays de la Loire
      musculoskeletal disorders (MSD) surveillance network. Eighty-three occupational
      health physicians included 3,710 employees between 2002 and 2005 and had to
      review them between 2007 and 2009. Thirteen of these physicians changed jobs and
      7 changed geographical sector in the same occupational health service. RESULTS:
      Another 94 physicians were contacted and 85 agreed to participate in the network.
      The follow-up rate was 43%: 1,044 employees were reviewed by the physician who
      saw them on inclusion and 567 employees were reviewed by another physician of the
      network. The other employees were distributed as follows: 25% were lost to follow
      up and their occupational status remained unknown; 23% were still employed with
      an identified occupational health physician but had not attended a medical visit
      during the follow-up study; 5% had left the occupational health surveillance
      system. Only 23 employees refused to participate in the follow-up and 105
      employees had a physician who refused to participate. DISCUSSION: There is
      therefore a considerable mobility of occupational health physicians, which
      interfered with follow-up despite their good mobilization and a high percentage
      of employee are lost to follow-up after having left their jobs. More appropriate
      systems must be set up to follow populations of employees, such as new
      collaborations with general practitioners.

PMID- 24893514
TI  - [Is smoking cessation part of the basic nursing education curriculum in Quebec? A
      survey of the program administrators].
AB  - INTRODUCTION: Basic nursing education has a major impact on the future
      professional practices of nurses. Nurses must be adequately trained to perform
      health promotion activities, such as smoking cessation. However, nurses play only
      a minor role in this field. The objective of this research was to describe the
      smoking cessation content in basic nursing programmes in Quebec. METHODS: A
      simple descriptive mixed design (quantitative and qualitative) study was
      conducted among nursing programme administrators in Quebec, using a validated
      online questionnaire. RESULTS: On average, the time devoted to smoking cessation
      was reported to be less than one hour per year, essentially concerning the
      physiological and pathophysiological factors of tobacco consumption, while
      nursing professional assessment and counselling in smoking cessation were almost
      non-existent. CONCLUSION: The results confirm the need to increase and improve
      the time and content devoted to smoking cessation in the basic nursing education
      curriculum. It is also important to structure basic training courses so to
      improve knowledge, attitudes, and skills of future nurses in order to influence
      their role in smoking cessation in their future professional practice.

PMID- 24893515
TI  - [Evaluation of medical information systems as a mean of identification of
      incident cases of colorectal cancer].
AB  - BACKGROUND: Cancer registries are a reliable source of data to estimate national
      cancer incidence rates, but they are not always available in all regions. This
      study assessed the value of medical information systems (PMSI) to identify
      incident cases of colorectal cancer METHODS: Two algorithms were elaborated to
      identify these incident cases in the PMSI database. The first algorithm was based
      on diagnosis and medical procedure codes and the second algorithm was based
      exclusively on diagnoses and the absence of diagnoses over the last five years.
      The results obtained for two departments were compared with those derived from
      two cancer registries, constituting the reference data. We then elaborated two
      multivariate logistic regression models to correct the national number of
      incident cases estimated by the algorithm adopted after evaluation of the
      results. RESULTS: The first algorithm provided results that were very close to
      those derived from the regional registries (646 vs 645 cases) with a good
      sensitivity and positive predictive value of 75%. The second algorithm
      overestimated the incidence by about 50% with a positive predictive value of 60%
      and was therefore not adopted for the national estimation. By applying the first
      algorithm to the national PMSI MCO database (medicine, surgery, obstetrics), and
      after modelling, the estimated incidence differed by only 2.34% compared to that
      observed by all 14 registries. The national estimation of cancer incidence was
      39,122 [37,020; 41,224] cases for 2005, which is consistent with the figure
      published by the Francim national registry network (37,413). CONCLUSION: This
      study demonstrates the value of PMSI data for estimation of national incidence
      rates for certain cancers in the absence of cancer registries. However, raw data
      must be corrected and can be achieved by the method proposed here.

PMID- 24893516
TI  - [Angers general practice residents' career projects in 2012].
AB  - OBJECTIVE: Medical demography and the geographical distribution of general
      practitioners (GPs) in the Pays de la Loire Region constitute a challenge to
      equitable primary care access. The objective of this study was to describe the
      career projects of Angers general practice residents in 2012 and to assess their
      knowledge of installation aids and their impact on practice choices. METHOD: A
      questionnaire-based declarative study was conducted in April 2012. RESULTS: 204
      out of 243 residents (84%) returned the questionnaire. Women represented 62% of
      responding residents. 56% of residents expressed their desire for predominantly
      outpatient general practice. A significant determinant in the choice of this type
      of practice was the voluntary choice of general practice during residency. Group
      practice was predominantly considered (86%), in semirural areas (60%). The
      administrative formalities to set up a general practice and the available aids
      were underestimated by 82% and 83% of residents, respectively. 91% of residents
      wanted to receive more information about administrative formalities and 82%
      considered that these aids could encourage their decision in favour of general
      practice. Anjou general practice residents appeared to be very attracted by
      outpatient general practice. CONCLUSION: This study shows that strategy of early
      contact with general practice in medical training should be continued.
      Information concerning the administrative formalities and aids available must be
      provided during medical training.

PMID- 24893517
TI  - [How to conduct public health surveillance? The example of the Observatoire
      Valaisan de la Sante in Switzerland].
AB  - OBJECTIVE: To describe the goals and methods of contemporary public health
      surveillance and to present the activities of the Observatoire Valaisan de la
      Sante (OVS), a tool unique in Switzerland to conduct health surveillance for the
      population of a canton. METHODS: Narrative review and presentation of the OVS.
      RESULTS: Public health surveillance consists of systematic and continuous
      collection, analysis, interpretation and dissemination of health data necessary
      for public health planning. Surveillance is organized according to contemporary
      public health issues. Switzerland is currently in an era dominated by chronic
      diseases due to ageing of the population. This "new public health" era is also
      characterized by the growing importance of health technology, rational risk
      management, preventive medicine and health promotion, and the central role of the
      citizen/patient. Information technologies provide access to new health data, but
      public health surveillance methods need to be adapted. In Switzerland, health
      surveillance activities are conducted by several public and private bodies, at
      federal and cantonal levels. The Valais canton has set up the OVS, an
      integrative, regional, and reactive system to conduct surveillance. CONCLUSION:
      Public health surveillance provides information useful for public health
      decisions and actions. It constitutes a key element for public health planning.

PMID- 24893518
TI  - [Taxonomies and typologies: not synonymous but complementary].

PMID- 24893519
TI  - [Taxonomy and typology: how to reconcile the conceptual frameworks of various
      schools of thought?].

PMID- 24893520
TI  - [The difficulties of access to health care for indigent living in non-poor
      households].
AB  - INTRODUCTION: To increase the financial access to health care for indigents, an
      action research was conducted in Burkina Faso. Based on a community approach,
      village committees identified indigents who were exempt from payment of health
      care fees. Quantitative analysis of the food expenditure of selected households
      (to assess the efficacy of the community-based selection) showed that some of the
      indigents selected came from households with a high economic level. This research
      was designed to explain why these people were identified by the Village Selection
      Committees (VSC). METHODS: This study was based on a qualitative exploratory
      descriptive approach, complementary and subsequent to a quantitative study. Life
      stories and individual interviews were conducted with stratified random sampling
      of 54 indigents. Thematic content analysis was performed. RESULTS: Indigents
      identified by the community are usually elderly, unable to work because of old
      age or chronic illness. However, some of them came from households with a high
      level of consumption, which can be explained by the fact that they benefit from
      community aid for their food needs. However, they present persistent difficulties
      of access to health care. DISCUSSION: The community perceives poverty in terms
      other simply economic aspects. The social dimension of poverty (including the
      inability to fully participate in community life) has a major impact on the
      choice of the CVS, leading to the selection of indigents from households that
      appear to have a high economic level. This community process which takes into
      account contextual factors, identified these people who do not necessarily have
      access to the household resources for health care.

PMID- 24893521
TI  - [Knowledge, and attitudes of Civil Society Organizations in the implementation of
      the Expanded Program on Immunization in Cote d'Ivoire].
AB  - INTRODUCTION: The objective of this study was to assess the level of involvement
      of leaders of Civil Society Organizations (CSOs) in implementation of routine EPI
      activities. METHODS: This was a cross-sectional descriptive study of the
      knowledge and attitudes of CSOs concerning implementation of routine EPI
      activities in the health district of Adiake (Cote d'Ivoire). RESULTS: This study
      shows that 77.1% of CSO leaders were literate and 92.9% of them were practicing
      Catholics or Muslims. They had a good knowledge of the existence of EPI (97.1%)
      and EPI target diseases, but were ignorant about the immunization schedule (82%).
      90% of CSO leaders considered EPI to be an important activity for the prevention
      of childhood diseases. They considered the reception in immunization units to be
      satisfactory (60%) and believed that rumours about the sterility of women were
      the cause of refusal of vaccination by communities. Although 41.4% of leaders had
      participated in social mobilization activities, none had participated in the
      mobilization of resources. DISCUSSION: Vaccination was not rejected by CSO
      leaders, but their lack of participation in implementation of EPI could induce
      errors and lead them to believe the rumours and refuse vaccination of their
      community. CONCLUSION: The effective integration of the socio-cultural bases of
      communities in which immunization programmes are conducted will promote the
      adhesion of the people responsible for these programmes.

PMID- 24893522
TI  - [Urban alcohol consumption among secondary school students in Cote d'Ivoire].
AB  - INTRODUCTION: Alcohol consumption is both a health and social risk factor. Few
      studies have been conducted on alcohol use among students in Cote d'Ivoire. This
      study was designed to determine factors associated with alcohol consumption among
      secondary school students in Cote d'Ivoire. METHODS: A cross-sectional study was
      conducted in May 2011 among public secondary school students in Abidjan. One
      class for each year of study was randomly selected. Multivariate analysis was
      conducted between alcohol consumption and independent variables. RESULTS: A total
      of 316 students participated in the survey. The mean age (SD) of the study
      population was 16.1 (2.7) years. One hundred and fourteen respondents (36.1%)
      reported having already drunk alcohol. Age of first alcohol consumption was 10-14
      years among girls (48.8%) and 15-19 years among boys (49.3%). Multivariate
      logistic regression identified the following factors associated with alcohol use
      among students: Christian religion, more pocket money, living with parents who
      drink alcohol and the student's perception of alcohol as a refreshing drink or
      having an antidepressant effect. CONCLUSION: In the light of the determinants of
      alcohol consumption and the students'suggestions in our study, it appears
      essential to involve students in actions concerning alcohol abuse.

PMID- 24893523
TI  - [National reference unit of neonatology: state of play].
AB  - BACKGROUND: The neonatal mortality rate in Mali is one of the highest in the
      world. Only one national reference neonatology unit is available in the country.
      AIM: To describe the time-course of morbidity, mortality, staff and accommodation
      facilities from 2008 to 2009 in Mali's unique national reference neonatology
      unit. METHODS: This descriptive and cross-sectional study was conducted in the
      neonatology unit of Gabriel Toure Teaching Hospital, Bamako. Data concerning
      staff number of admissions, sex ratio, diseases, patients outcome, capacity and
      length-of-stay were compiled for the period from 1st January 2008 to 31 December
      2012. RESULTS: Medical staff increased from one to three in 2009 and the number
      of nurses and midwives decreased from 16 to 14 with an average number of beds of
      44. The mean number of hospitalizations per year was 3,900 (range: 3667-4585)
      with 14% of in-born deliveries and a mean length-of-stay of 3.7 days. Prematurity
      birth asphyxia and infection represented 80.5% of reasons for admission and 79.5%
      of deaths. The mortality rate varied from 28.5% to 36.8% with an annual mean of
      33.2%. The diseases associated with the highest mortality were tetanus (60.8%),
      prematurity (42.7%), birth asphyxia (29.4%) and infection (25.7%). CONCLUSION:
      Neonatal mortality remains very high in Mali. Health authorities should take
      measures to decentralize the care of sick newborns in order to reduce neonatal
      mortality in Mali.

PMID- 24893524
TI  - [Epidemiological, clinical and judicial aspects of sexual assault in Bamako
      (Mali)].
AB  - BACKGROUND: Sexual assault rates are underestimated in Mali. This study was
      designed to assess the epidemiological, clinical and judicial aspects of sexual
      assault. PATIENTS AND METHOD: A retrospective study was conducted from 1st July
      2007 to 30 April 2010 in the health care centre of the 4th Commune of Bamako. The
      study included 37 sexual assault victims selected from the medical records and
      sexual assault certificates from a total of 1,810 patients attending the
      gynaecology clinic during the study period. RESULTS: The frequency of sexual
      assault was therefore 2%. 78.4% of the victims took legal action against the
      alleged perpetrator. Victims admitted at the request of Police officers accounted
      for 43.25%; 59.5% of victims attended the clinic within 24 hours following the
      assault. The age ranged from 2 to 40 years with a mean of 21 years; 37.9% were
      single and 48.6% were students. The assault was perpetrated by one person in
      89.2%, a relative was involved in 5.4%; rape consisted of genito-genital
      intercourse in 64.9%; 32.4% of the victims had perineal and/or vulval injuries.
      CONCLUSION: Sexual assault is relatively frequent in Mali, particularly among
      students and housewives. It represents a real tragedy, which must be prevented by
      increasing the awareness of the population, judicial assistance to victims and
      prosecution of perpetrators.

PMID- 24893525
TI  - [Study of determinants of rape in minors in the Kolda region of Senegal].
AB  - INTRODUCTION: The objective of this study was to investigate the determinants of
      rape among minors in the Kolda region. METHODOLOGY: A retrospective, cross
      sectional, descriptive and analytical was conducted from 23 December 1992 to 31
      December 2011, based on the charts of rape victims under the age of 18 years.
      Sampling was complete. Bivariate and multivariate analyses were performed using
      Epi Info 3.3.2 and R 2.9.2 software, respectively. RESULTS: The study included
      162 cases of sexual assault. The mean age of victims was 12.3 +/- 3 years (range:
      4-17 years). The mean age of perpetrators of sexual assault was 26.4 +/- 9.5
      years and minors accounted for 13% of perpetrators. 54.9% of victims, were raped.
      Victims of sexual assault knew the perpetrator in 66% of cases and were attacked
      in broad daylight in 53.4% of cases. The perpetrators were drunk at the time of
      sexual assault in 15.3% of cases. The assault took place in the bush (14.8%).
      Twenty eight percent (28%) of rapists were jailed and 38.6% of them were jailed
      for between 5 and 10 years. Sexual assault in the bush [adjusted OR = 3.46 (1.02
      11.77)] and intoxication of the perpetrator at the time of sexual assault
      [adjusted OR = 3.47 (1.04-11.61)] were associated with a high risk of rape. In
      contrast, victims who knew their assailants were at a lower risk of rape
      [adjusted OR = 0.09 (0.03 to 0.24)]. CONCLUSION: Extension of this study to the
      national scale would provide health and judicial authorities with an overview of
      sexual assault among minors, to allow more effective prevention at the national
      level.

PMID- 24893526
TI  - Medicine and the humanities--doctors as artists.

PMID- 24893527
TI  - A multidisciplinary approach to cardiac rehabilitation in SA.

PMID- 24893528
TI  - The effects of obesity, smoking, and excessive alcohol intake on healthcare
      expenditure in a comprehensive medical scheme.

PMID- 24893529
TI  - LCHF: response to Drs Boyles and Wasserman.

PMID- 24893530
TI  - LCHIF: response to Dr Evenepoel.

PMID- 24893531
TI  - LCHF: response to Dr Kapp.

PMID- 24893532
TI  - Activists warn: don't fall victim to our HIV successes.

PMID- 24893534
TI  - Withholding or withdrawing treatment and palliative treatment hastening death:
      the real reason why doctors are not held legally liable for murder.
AB  - Doctors who hasten the termination of the lives of their patients by withholding
      or withdrawing treatment or prescribing a potentially fatal palliative dose of
      medication satisfy the elements of intention and causation of a charge of murder
      against them. However, the courts have held that, for policy reasons based on
      'society's legal convictions', such conduct is not unlawful if the patient
      consented to it or medical treatment would be futile or palliative treatment may
      hasten death. Doctors are not held liable for murder because society regards
      their omissions or acts as lawful--not because they did not have the intention in
      law to kill or did not cause the death of their patients.

PMID- 24893535
TI  - Strengthening pharmacovigilance in South Africa.
AB  - This report outlines findings and recommendations of a national pharmacovigilance
      workshop held in August 2012 in South Africa (SA). A survey of current
      pharmacovigilance activities, conducted in preparation for the meeting,
      identified multiple programmes collecting drug safety data in SA, with limited co
      ordination at national level. The meeting resolved that existing
      pharmacovigilance programmes need to be strengthened and consolidated to ensure
      that important local safety issues are addressed, data can be pooled and compared
      and outputs shared more widely. Pharmacovigilance activities should inform
      treatment guidelines with the goal of improving patient care. A variety of
      pharmaco-epidemiological approaches should be employed, including nesting drug
      safety studies within existing sentinel cohorts and the creation of a pregnancy
      exposure registry. The attendees agreed on key principles that will inform a
      national pharmacovigilance plan and compiled a list of priority pharmacovigilance
      issues facing public health programmes in SA.

PMID- 24893536
TI  - Surgery and anaesthesia in art: the contribution of Dorothy Kay.
AB  - Dorothy Kay, the acclaimed Irish-born Port Elizabeth artist, married Dr Hobart
      Kay, FRCSI, in Cape Town, South Africa, in 1910. She was an exceptional portrait
      painter, whose astute observation of detail and ability to empathise with her
      subject and convey character brought her much important work. Her traditional
      British realist-school style of painting, and ability to depict mechanical
      equipment accurately, led to several industrial commissions. In 1937 these skills
      combined to produce her largest painting, 'Surgery' which depicts a patient
      undergoing an abdominal operation in a Port Elizabeth hospital. The painting
      graphically captures the skill and care exhibited by the anaesthetist, together
      with the anaesthetic equipment used at that time. During the war Dorothy became
      an accredited war artist. Eight of her wartime paintings were purchased by the
      Union Government and are now housed in the Ditsong National Museum of Military
      History in Saxonwold, Johannesburg. Two of these paintings of medical interest
      are discussed. The first, entitled 'Operation in a Base Hospital, depicts surgery
      being performed in a base hospital and is very similar in composition to
      'Surgery' The second, entitled 'Blood to Save Lives, portrays a volunteer
      donating blood.

PMID- 24893537
TI  - The 'medical humanities' in health sciences education in South Africa.
AB  - A new masters-level course, 'Medicine and the Arts" will be offered in 2014 at
      the University of Cape Town, setting a precedent for interdisciplinary education
      in the field of medical humanities in South Africa. The humanities and social
      sciences have always been an implicit part of undergraduate and postgraduate
      education in the health sciences, but increasingly they are becoming an explicit
      and essential component of the curriculum, as the importance of graduate
      attributes and outcomes in the workplace is acknowledged. Traditionally, the
      medical humanities have included medical ethics, history, literature and
      anthropology. Less prominent in the literature has been the engagement with
      medicine of the disciplines of sociology, politics, philosophy, linguistics,
      education, and law, as well as the creative and expressive arts. The development
      of the medical humanities in education and research in South Africa is set to
      expand over the next few years, and it looks as if it will be an exciting inter
      disciplinary journey.

PMID- 24893538
TI  - The intercalated BSc (Med) Honours/MB ChB and integrated MB ChB/PhD tracks at the
      University of Cape Town: models for a national medical student research training
      programme.
AB  - The Faculty of Health Sciences at the University of Cape Town is addressing the
      shortage of clinician-scientists in South Africa by introducing two research
      training tracks in parallel with the professional MB ChB programme, namely the
      intercalated BSc (Med) Hons/MB ChB track and the integrated MB ChB/PhD track. The
      BSc (Med) Hons/MB ChB track is available to MB ChB students who have completed
      the first two years of study. The track comprises a course in Molecular Medicine
      given concurrently with the MB ChB third-year curriculum, followed by a BSc (Med)
      Hons as a 'year out' of MB ChB. Subsequently students may enroll into the
      integrated MB ChB/PhD track that enables them to undertake a PhD concurrently
      with MB ChB studies, which will be spread over additional years, or alternatively
      to undertake a PhD after completion of the MB ChB. These tracks, which were
      launched in 2011, represent an opportunity to train a new cadre of young African
      clinician-scientists at the undergraduate level.

PMID- 24893539
TI  - Palliative care in chronic disease.

PMID- 24893540
TI  - A new mental health policy for South Africa.

PMID- 24893541
TI  - Failing to numb the pain: the untreated epidemic.

PMID- 24893542
TI  - Maintaining wellbeing for South Africans receiving ART: the burden of pain and
      symptoms is greater with longer ART exposure.
AB  - BACKGROUND: Physical and psychological symptom burden among people with HIV
      infection is associated with poor quality of life, poorer treatment adherence,
      viral rebound and risk behaviour. Symptomatology has not been investigated among
      outpatients in sub-Saharan Africa. OBJECTIVE: To measure the seven-day period
      prevalence, burden and correlates of pain and other physical and psychological
      symptoms among HIV patients receiving antiretroviral therapy (ART). METHODS: This
      was a cross-sectional self-report study. A total of 378 patients were interviewed
      using validated tools in three South African public sector clinics. RESULTS: The
      most prevalent symptoms were feeling sad (64%), feeling irritable (61.6%), worry
      (60.8%), numbness and tingling in hands/ feet (59.8%), and sexual problems (51%).
      In multivariate analysis, later disease stage was associated with worse
      psychological symptom burden (beta = 0.359; 95% confidence interval (CI) 0.202 -
      0.516; p < or = 0.001), global symptom burden (beta = 0.365; 95% CI 0.204 -
      0.526; p < 0.001) and number of symptoms (beta = 0.308; 95% CI 0.150 - 0.465; p <
      0.001). Those receiving treatment for a greater number of years also reported
      higher burden for physical (beta = 0.083; 95% CI 0.037 - 0.129; p < or = 0.001),
      psychological (beta = 0.068; 95% CI 0.019 - 0.117; p = 0.007) and global symptoms
      (beta = 0.065; 95% CI 0.016 - 0.115; p = 0.010), and a greater number of symptoms
      (beta = 0.081; 95% CI 0.032 - 0.130; p = 0.001). CONCLUSIONS: The data reveal a
      high symptom burden despite treatment. Detailed symptom assessment and control
      continues to be required in the era of treatment.

PMID- 24893543
TI  - A 5-year analysis of the helicopter air mercy service in Richards Bay, South
      Africa.
AB  - BACKGROUND: A helicopter emergency medical service (HEMS) was established in 2005
      in Richards Bay, KwaZulu-Natal, South Africa, to provide primary response and
      inter-facility transfers to a largely rural area with a population of 3.4 million
      people. OBJECTIVE: To describe the first 5 years of operation of the HEMS.
      METHODS: A chart review of all flights from 1 January 2006 to 31 December 2010
      was conducted. RESULTS: A total of 1 429 flights were undertaken; 3 were excluded
      from analysis (missing folders). Most flights (88.4%) were inter-facility
      transfers (IFTs). Almost 10% were cancelled after takeoff. The breakdown by age
      was 61.9% adult, 15.1% paediatric and 21.6% neonate. The main indications for
      IFTs were obstetrics (34.5%), paediatrics (27.9%) and trauma (15.9%). For primary
      response most cases were trauma (72.9%) and obstetrics (11.3%). The median on
      scene time for neonates was significantly longer (48 min, interquartile range
      (IQR) 35 - 64 min) than that for adults (36 min, IQR 26 - 48; p < 0.001) and
      paediatrics (36 min, IQR 25 - 51; p < 0.02). On-scene times for doctor-paramedic
      crews (45 min, IQR 27 - 50) were significantly longer than for paramedic-only
      crews (38 min, IQR 27 - 57; p < 0.001). CONCLUSION: The low flight-to-population
      ratio and primary response rate may indicate under-utilisation of the air medical
      service in an area with a shortage of advanced life support crews and long
      transport distances. Further studies on HEMSs in rural Africa are needed,
      particularly with regard to cost-benefit analyses, optimal activation criteria
      and triage systems.

PMID- 24893544
TI  - The cost of harmful alcohol use in South Africa.
AB  - BACKGROUND: The economic, social and health costs associated with alcohol-related
      harms are important measures with which to inform alcohol management policies and
      laws. This analysis builds on previous cost estimates for South Africa. METHODS:
      We reviewed existing international best-practice costing frameworks to provide
      the costing definitions and dimensions. We sourced data from South African
      costing literature or, if unavailable, estimated costs using socio-economic and
      health data from secondary sources. Care was taken to avoid possible causes of
      cost overestimation, in particular double counting and, as far as possible,
      second-round effects of alcohol abuse. RESULTS: The combined total tangible and
      intangible costs of alcohol harm to the economy were estimated at 10 - 12% of the
      2009 gross domestic product (GDP). The tangible financial cost of harmful alcohol
      use alone was estimated at R37.9 billion, or 1.6% of the 2009 GDP. DISCUSSION:
      The costs of alcohol-related harms provide a substantial counterbalance to the
      economic benefits highlighted by the alcohol industry to counter stricter
      regulation. Curtailing these costs by regulatory and policy interventions
      contributes directly and indirectly to social well-being and the economy.
      CONCLUSIONS; Existing frameworks that guide the regulation and distribution of
      alcohol frequently focus on maximising the contribution of the alcohol sector to
      the economy, but should also take into account the associated economic, social
      and health costs. Current interventions do not systematically address the most
      important causes of harm from alcohol, and need to be informed by reliable
      evidence of the ongoing costs of alcohol-related harms.

PMID- 24893545
TI  - Attitudes to organ donation among some urban South African populations remain
      unchanged: a cross-sectional study (1993 - 2013).
AB  - BACKGROUND: A 1993 paper in the SAMJ suggested that public attitudes to organ
      donation in South Africa were positive. However, statistics reveal a decline in
      the annual number of transplants in this country. OBJECTIVE: To repeat the 1993
      survey as far as possible and determine whether public attitudes to organ
      donation in some South African populations have changed over the past 20 years.
      METHODS: The 1993 study was replicated in 2012 to generate a current data set.
      This was compared with the raw data from the 1993 study, and an analysis of
      percentages was used to determine variations. RESULTS: Generally attitudes to
      organ donation have not changed since 1993, remaining positive among the study
      population. However, individuals are significantly more hesitant to consider
      donating the organs of a relative without being aware of that person's donation
      preference. Individuals in the black African study population are currently more
      willing to donate kidneys than in 1993 (66% v. 81%; p < 0.0001), but less willing
      to donate a heart (64% v. 38%; p < 0.0001), a liver (40% v. 34%; p < 0.036) and
      corneas (22% v. 15%, p < 0.0059). CONCLUSIONS: Publicity campaigns aimed at
      raising awareness of organ donation should emphasise the importance of sharing
      donation preferences with one's family in order to mitigate discomfort about
      making a decision on behalf of another. These campaigns should be culturally and
      linguistically sensitive. The study should be repeated in all populations over
      time to continually gauge attitudes.

PMID- 24893546
TI  - A point-prevalence survey of public hospital inpatients with palliative care
      needs in Cape Town, South Africa.
AB  - OBJECTIVES: To assess the need for palliative care among inpatients occupying
      acute beds in the public sector hospitals of the Cape Town Metropole. METHODS: A
      cross-sectional, contemporaneous, point-prevalence study was performed at 11
      public sector hospitals in the Cape Town Metropole using a standardised
      palliative care identification tool. Data were collected on the socio-demographic
      characteristics, diagnoses, and prior and current care planning of patients.
      RESULTS: The case notes of 1 443 hospital inpatients were surveyed, and 16.6%
      were found to have an active life-limiting disease. The mean age of the group was
      56 years. The diagnoses were cancer in 50.8%, organ failure in 32.5%, and
      HIV/tuberculosis in 9.6%. The greatest burden of disease was in the general
      medical wards, to which an overall 54.8% of patients meeting the requirements for
      palliative care were admitted. CONCLUSIONS: This study provides evidence for the
      need for palliative care services in public sector hospitals and in the health
      system as a whole. The young age of patients and the high prevalences of end
      stage renal failure and HIV are unique, and the burden in the general medical
      wards suggests a focus for initial inpatient programmes.

PMID- 24893547
TI  - Vascular disease--everyone's problem.

PMID- 24893548
TI  - Anticoagulation: where have we come from and where are we going? The evidence for
      and against novel anticoagulants.
AB  - Warfarin, one of the vitamin K antagonists, has been used since 1940, when it was
      first approved for the treatment of venous thromboembolism. It is currently the
      most commonly used anticoagulant, although alternative drugs are available, such
      as aspirin, clopidogrel and dipyridamol, which have been studied in a number of
      scenarios. The newest agents available to clinicians are the broad group of novel
      anticoagulants, such as direct thrombin and direct factor Xa inhibitors,
      including molecules such as dabigatran, rivaroxaban, apixaban and edoxaban.

PMID- 24893549
TI  - Rethinking our services.

PMID- 24893550
TI  - Striking a professional balance: interactions between nurses and their older
      rural patients.
AB  - Close relationships between older adults and their health-care professionals in
      community settings can enhance wellbeing and support positive health in older
      age. In rural areas, health-care workers may know their patients socially as well
      as professionally, and roles are mediated. This article reports the findings from
      16 qualitative interviews with older adults and health and social care
      professionals in rural areas of Wales. The study found that the sharing of
      nonclinical information in rural home-care situations is both likely and
      desirable, supporting the sense of social connectedness experienced by the older
      adult, contributing towards the development of the nurse/carer-client
      relationship and improving older adult wellbeing. However, it is recognised that
      there is potential for boundaries to become blurred and, in some situations,
      nurses and carers may need support to negotiate the divide between appropriate
      and inappropriate disclosure while maintaining a close relationship with the
      older adult.

PMID- 24893551
TI  - End-of-life training for paid carers working with people with learning
      disabilities.
AB  - People with learning disabilities are living longer lives. Over the past few
      years, research has explored the needs of people with learning disabilities,
      their families and learning disability professionals in relation to end-of-life
      care and death. However, little is known about the needs of paid carers and their
      experience of end-of-life care. This article discusses the development,
      implementation and evaluation of a study day about end-of-life care that was
      delivered to paid carers on two separate occasions in Berkshire Healthcare NHS
      Foundation Trust. A total of 43 paid carers attended and the days were well
      evaluated. The need for further training for paid carers who work with people
      with learning disabilities at the end of life was highlighted.

PMID- 24893552
TI  - Promoting intermittent self-catheterisation to encourage self-care in district
      nursing patients.
AB  - Intermittent self-catheterisation (ISC) is deemed the preferred option for the
      management of urinary incontinence and/or retention in patients requiring a
      catheter. It also allows patients to self-care, thereby placing fewer demands on
      district nursing (DN) services and meeting the requirements of the current health
      policy agenda. Yet many patients who could benefit from ISC in the community
      still use a long-term urinary catheter. This may contribute to increased
      morbidity, poorer quality of life, and unnecessary visits from the DN team. This
      article analyses the role of the district nurse in promoting and supporting the
      use of ISC with suitable patients.

PMID- 24893553
TI  - The impact of the enhanced recovery after surgery (ERAS) programme on community
      nursing.
AB  - Early discharge from hospital as a result of enhanced recovery after surgery
      (ERAS) programmes can be both positive and frightening experiences for surgical
      patients. In a recently published article by the authors in the British Journal
      of Nursing, participants described mixed reactions to the ERAS programme,
      highlighting the period of home convalescence as being particularly challenging.
      In this article the concept of ERAS is explained, followed by an overview of the
      research study which led to the authors highlighting the issue of home
      convalescence. The interventions that have already been established locally as a
      result of this research are explored, as is the potential impact that both these
      short hospital stays and further necessary interventions might have on community
      nursing. The article examines whether health professionals are sufficiently
      easing the pressures of self-recoveryto fill the apparent'void' that the study
      participants described as existing between hospital care and community follow-up.

PMID- 24893554
TI  - Achieving success in commissioning services.

PMID- 24893555
TI  - The role of the sign-off mentor in the community setting.
AB  - In an move to identify nursing as an all-graduate profession, the Nursi Midwifery
      Council standards identified that future nurses need to be equipped with the
      skills and knowledge to lead and deliver high-quality care. Inorder to have these
      skills within the changing context of health care, students need to experience
      care delivery across a range of community, hospital and other settings. Students
      have to undertake a final clinical placement of 12 weeks at the end of their
      programme, commonly called a consolidation placement, and are allocated a sign
      off mentor to confirm they meet the requirements for entry to the register.
      Placement capacity within primary care settings continues to be a challenge
      alongside the need for providing a sign-off mentor. This article discusses some
      of the challenges and opportunities of the role of the sign-off mentor and the
      potential impact for encouraging newly qualified recruitment in this area.

PMID- 24893556
TI  - Domestic violence disclosure scheme: a guide to Clare's Law for district nurses.
AB  - The Government is rolling out a national Domestic Violence Disclosure Scheme from
      March 2014 that will allow people who are worried that they may be at risk of
      violence from their new partner to ask police whether they have a past history of
      domestic abuse. This article considers the value of the scheme and the role that
      district nurses must take in promoting the scheme as part of their intervention
      and support in domestic violence cases.

PMID- 24893557
TI  - Does humour have a place in palliative care?

PMID- 24893558
TI  - A letter to the editor re: 'relationships between community nurses and other
      health-care professionals'.

PMID- 24893559
TI  - 25 years of the internet.

PMID- 24893560
TI  - Low-dose aspirin for the prevention of adverse pregnancy outcomes in women with
      elevated alpha-fetoprotein.

PMID- 24893561
TI  - Surgical management of an epithelioid hemangioendothelioma of the superior vena
      cava protruding into the right atrium.
AB  - Epithelioid hemangioendothelioma (EH) is a rare malignant tumor of vascular
      origin that often involves soft tissues and visceral organs, and less commonly,
      large veins. We report a case of EH of the superior vena cava protruding into the
      right atrium and its surgical management.

PMID- 24893563
TI  - Structural changes in dermal collagen and oxidative stress levels in the skin of
      Japanese overweight males.
AB  - OBJECTIVE: It has been reported that obese people have poorly organized dermal
      collagen structure because of the degradation of collagen fibers, which is caused
      by an increase in oxidative stress levels associated with the hypertrophy of
      subcutaneous adipose cells. However, it is unclear whether an increase in
      oxidative stress levels caused by the accumulation of subcutaneous adipose tissue
      and a change in the dermal structure also occur in overweight and obese Japanese
      people. The objectives of this study are to identify structural changes that
      occur in the dermis and to measure the levels of oxidative stress in Japanese
      overweight males. METHODS: The overweight group included 43 Japanese male
      volunteers aged between 25 and 64 years and with a body mass index (BMI) of >=25
      and <30. The control group included 47 male volunteers aged between 22 and 64
      years and with BMI of <25. The 20-MHz Dermascan C(r) ultrasound scanner with
      software for image analyses was used. Echogenicity of the upper and lower dermis
      was measured. The mRNA expression level of heme oxygenase-1 (HMOX1) in hair
      follicles was quantitatively analyzed by real-time reverse transcription
      polymerase chain reaction (RT-PCR) and was used as a marker of oxidative stress.
      Ultrasonographic imaging and collection of hair follicles were performed at the
      same site on the thigh, abdomen, and upper arm. RESULTS: The HMOX1 mRNA
      expression level in the abdomen and thigh was significantly lower in the
      overweight group than in the control group. Moreover, the echogenicity of the
      upper dermis of the abdomen and the lower dermis of the abdomen and thigh was
      significantly lower in the overweight group than in the control group.
      CONCLUSION: We detected an increase in oxidative stress levels and a decrease in
      the density of dermal collagen at the same site on the thigh, abdomen, and upper
      arm of Japanese overweight males. These findings suggest the fragility of the
      dermis of Japanese overweight males, which might have been caused by the
      accumulation of subcutaneous adipose tissue.

PMID- 24893562
TI  - Crossroads between light response and nutrient signalling: ENV1 and PhLP1 act as
      mutual regulatory pair in Trichoderma reesei.
AB  - BACKGROUND: Crosstalk between the signalling pathways responding to light-dark
      cycles and those triggering the adaptation of metabolism to the environment is
      known to occur in various organisms. This interrelationship of light response and
      nutrient sigalling is crucial for health and fitness. The tropical ascomycete
      Trichoderma reesei (syn. Hypocrea jecorina) represents one of the most efficient
      plant cell wall degraders. Regulation of the enzymes required for this process is
      affected by nutritional signals as well as other environmental signals including
      light. Therefore we aimed to elucidate the interrelationship between nutrient and
      light signaling and how the light signal is transmitted to downstream pathways.
      RESULTS: We found that the targets of the light regulatory protein ENV1 in light
      show considerable overlap with those of the heterotrimeric G-protein components
      PhLP1, GNB1 and GNG1. Detailed investigation of a regulatory interrelationship of
      these components with ENV1 under conditions of early and late light response
      indicated a transcriptional mutual regulation between PhLP1 and ENV1, which
      appears to dampen nutrient signalling during early light response, presumably to
      free resources for protective measures prior to adaptation of metabolism to
      light. Investigating the downstream part of the cascade we found support for the
      hypothesis that ENV1 is necessary for cAMP mediated regulation of a considerable
      part of the core functions of the output pathway of this cascade, including
      regulation of glycoside hydrolase genes and those involved in nitrogen, sulphur
      and amino acid metabolism. CONCLUSIONS: ENV1 and PhLP1 are mutual regulators
      connecting light signaling with nutrient signaling, with ENV1 triggering the
      output pathway by influencing cAMP levels.

PMID- 24893564
TI  - Insufficient regional anaesthesia in patients with abdominoplasty.

PMID- 24893565
TI  - Between-sex genetic covariance constrains the evolution of sexual dimorphism in
      Drosophila melanogaster.
AB  - Males and females share much of their genome, and as a result, intralocus sexual
      conflict is generated when selection on a shared trait differs between the sexes.
      This conflict can be partially or entirely resolved via the evolution of sex
      specific genetic variation that allows each sex to approach, or possibly achieve,
      its optimum phenotype, thereby generating sexual dimorphism. However, shared
      genetic variation between the sexes can impose constraints on the independent
      expression of a shared trait in males and females, hindering the evolution of
      sexual dimorphism. Here, we examine genetic constraints on the evolution of
      sexual dimorphism in Drosophila melanogaster cuticular hydrocarbon (CHC)
      expression. We use the extended G matrix, which includes the between-sex genetic
      covariances that constitute the B matrix, to compare genetic constraints on two
      sets of CHC traits that differ in the extent of their sexual dimorphism. We find
      significant genetic constraints on the evolution of further dimorphism in the
      least dimorphic traits, but no such constraints for the most dimorphic traits. We
      also show that the genetic constraints on the least dimorphic CHCs are
      asymmetrical between the sexes. Our results suggest that there is evidence both
      for resolved and ongoing sexual conflict in D. melanogaster CHC profiles. 

PMID- 24893566
TI  - Cysteine desulphurase plays an important role in environmental adaptation of the
      hyperthermophilic archaeon Thermococcus kodakarensis.
AB  - The sulphur atoms of sulphur-containing cofactors that are essential for numerous
      cellular functions in living organisms originate from L-cysteine via cysteine
      desulphurase (CSD) activity. However, many (hyper)thermophilic archaea, which
      thrive in solfataric fields and are positioned near the root of the evolutionary
      tree of life, lack CSD orthologues. The existence of CSD orthologues in a subset
      of (hyper)thermophilic archaea is of interest with respect to the evolution of
      sulphur-trafficking systems for the cofactors. This study demonstrates that the
      disruption of the csd gene of Thermococcus kodakarensis, a facultative elemental
      sulphur (S(0))-reducing hyperthermophilic archaeon, encoding Tk-CSD, conferred a
      growth defect evident only in the absence of S(0), and that growth can be
      restored by the addition of S(0), but not sulphide. We show that the csd gene is
      not required for biosynthesis of thiamine pyrophosphate or molybdopterin,
      irrespective of the presence or absence of S(0), but is necessary for iron
      sulphur cluster biosynthesis in the absence of S(0). Recombinant form of Tk-CSD
      expressed in Escherichia coli was obtained and it was found to catalyse the
      desulphuration of L-cysteine. The obtained data suggest that hyperthermophiles
      might benefit from a capacity for CSD-dependent iron-sulphur cluster biogenesis,
      which allows them to thrive outside solfataric environments.

PMID- 24893567
TI  - Barriers among Danish women and general practitioners to raising the issue of
      intimate partner violence in general practice: a qualitative study.
AB  - BACKGROUND: Thirty-five percent of Danish women experience sexual or physical
      violence in their lifetime. However, health care professionals are not in the
      practice of asking about intimate partner violence (IPV) in Denmark. It is
      currently unknown what hinders general practitioners from asking about partner
      violence and how Danish women would perceive such an inquiry. This aspect has not
      previously been explored in Denmark. An exploratory study was conducted to
      examine what hinders general practitioners (GPs) from asking and what Danish
      women's views and attitudes are regarding being asked about IPV. METHODS: Data
      were collected through individual and group interviews with a sample of three GPs
      and a diverse sample of 13 women, including both survivors of partner violence
      and those without any history of partner violence. An interpretative analysis was
      performed with the data. RESULTS: This study provides important knowledge
      regarding the barriers and attitudes towards inquiry about IPV in primary care in
      Denmark. Results indicate that Denmark is facing the same challenges when
      responding to survivors of IPV as other similar countries, including Sweden,
      Norway, the UK, USA, and Australia. Danish women want general practitioners to
      ask about violence in a respectful and non-judgemental manner. However, general
      practitioners are resistant towards such an inquiry and would benefit from
      training regarding how to respond to women who have been exposed to IPV.
      CONCLUSIONS: It is acceptable to inquire about IPV with women in Denmark in a non
      judgemental and respectful way. Informing about IPV prevalence is important prior
      to the inquiry. However, general practitioners require more awareness and
      training before a favourable environment for this change in procedure can be
      created. Further large-scale research is needed to support the evidence generated
      by this small study.

PMID- 24893570
TI  - Asymmetric conjugate addition of alkylzirconium reagents to alpha,beta
      unsaturated lactones.
AB  - The asymmetric synthesis of beta-substituted lactones by catalytic asymmetric
      conjugate addition of alkyl groups to alpha,beta-unsaturated lactones is
      reported. The method uses alkylzirconium nucleophiles prepared in situ from
      alkenes and the Schwartz reagent. Enantioselective additions to 6- and 7-membered
      lactones proceed at rt, tolerate a wide variety of functional groups, and are
      readily scalable. The method was used in a formal asymmetric synthesis of
      mitsugashiwalactone. 

PMID- 24893569
TI  - Robust and flexible fabrication of chemical micropatterns for tumor spheroid
      preparation.
AB  - A robust and flexible approach is described for the straightforward preparation
      of multicellular tumor spheroids of controllable dimensions. The approach is
      based on a one-step plasma polymerization of the monomer allylamine carried out
      through conformal micropatterning physical masks that is used to deposit amine
      rich (PolyAA) micrometer-scale features that promote cellular attachment and
      initiate the formation of multicellular spheroids. A simple backfilling step of
      the nonpolymerized poly(dimethylsiloxane) background with Pluronic F127
      significantly reduced background cellular adhesion on the untreated substrate
      and, in turn, improved the quality of the spheroid formed. Tumor cells grown on
      the PolyAA/F127 patterned surfaces reliably formed multicellular spheroids within
      24-48 h depending on the cell type. The dimension of the spheroids could be
      readily controlled by the dimension of the amine-rich micropatterns. This simple
      approach is compatible with the long-term culture of multicellular spheroids and
      their characterization with high-resolution optical microscopy. These features
      facilitate the development of on-chip assays, as demonstrated here for the study
      of the binding of transferrin-functionalized gold nanoparticles to multicellular
      tumor spheroids. 

PMID- 24893568
TI  - Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast
      cancer risk: a meta-analysis.
AB  - BACKGROUND: The base excision repair (BER) pathway removes DNA damage caused by
      ionizing radiation, reactive oxidative species and methylating agents. OGG1 and
      APE1 are two important genes in the BER pathway. Many epidemiological studies
      have evaluated the association between polymorphisms in the two BER genes (OGG1
      Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are
      inconsistent. METHODS: We searched the electronic databases including PubMed,
      Embase and Cochrane library for all eligible studies for the period up to
      February 2014. Data were extracted by two independent authors and pooled odds
      ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to
      assess the strength of the association. RESULTS: A total of 17 studies including
      9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism
      and 7 studies containing 2,979 cases and 3,111 controls were included for APE1
      Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not
      find a significant association with breast cancer risk when all eligible studies
      were pooled into the meta-analysis. However, in subgroup analyses by ethnicity
      and menopausal status, statistical significant increased breast cancer risk was
      found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321,
      P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and
      postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003
      1.346, P=0.024). In subgroup analysis according to quality score, source of
      control, and HWE in controls, no any significant association was detected. With
      respect to APE1 Asp148Glu polymorphism, no significant association with breast
      cancer risk was demonstrated in the overall and stratified analyses. CONCLUSIONS:
      The present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a
      risk factor for breast cancer in Asians and postmenopausal patients. Further
      large and well-designed studies are needed to confirm this association. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.

PMID- 24893571
TI  - Metastasis of osteosarcoma to the trapezius muscle: a case report.
AB  - Metastasis of a primary osteosarcoma to the muscles is extremely rare. As there
      have been few reported cases, the necessity of surgical treatment for such
      metastatic lesions remains controversial. We present the case of a primary
      osteosarcoma with development of a solitary metastasis to the trapezius muscle
      during chemotherapy for pulmonary metastasis. The patient was a 51-year-old man
      diagnosed with osteosarcoma of the right tibia. After undergoing chemotherapy and
      femoral amputation, he developed pulmonary metastasis. Chemotherapy was
      reinitiated, however, after approximately 1 year a palpable tumor was identified
      in the patient's right shoulder. This tumor grew and was associated with pain in
      the right shoulder. It was surgically removed 3 years after the re-initiation of
      chemotherapy. The pathological diagnosis was osteosarcoma with metastasis to the
      trapezius muscle. Although the patient died of respiratory failure due to
      pulmonary metastasis 14 months after resection of the metastatic lesion in the
      trapezius muscle, no new extrapulmonary metastasis was observed after the
      resection. 

PMID- 24893572
TI  - Similar bleeding phenotype in young children with haemophilia A or B: a cohort
      study.
AB  - The bleeding phenotype has been suggested to differ between haemophilia A and B.
      More knowledge on the bleeding phenotype at initiation of treatment is important
      to optimize patient care. The aim of this study was to investigate the severity
      of the bleeding phenotype and the variation in bleeding in children with severe
      or moderate haemophilia A and B. Consecutive, previously untreated patients with
      severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01
      0.05 IU mL(-1) respectively) born between January 1st 2000 and January 1st 2010
      were included. Primary outcome was severity of bleeding tendency. Secondary
      outcome was variation in bleeding pattern. A total of 582 patients with severe
      haemophilia A and 76 with severe haemophilia B did not differ in age at first
      exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed
      (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20
      years, P = 0.59). Patients with moderate haemophilia were older compared to
      patients with severe haemophilia. In patients with moderate haemophilia there
      were no clear differences between haemophilia A and B. Severity and variation in
      bleeding phenotype are similar during the early stage of treatment in patients
      with severe and moderate haemophilia A and B respectively. The findings imply
      that children with haemophilia B should be observed and treated as vigilantly as
      those with haemophilia A. 

PMID- 24893575
TI  - Sebacinales, but not total root associated fungal communities, are affected by
      land-use intensity.

PMID- 24893574
TI  - Genetic polymorphism related to exfoliative glaucoma is also associated with
      primary open-angle glaucoma risk.
AB  - BACKGROUND: To investigate the possible association of the rs2165241 polymorphism
      (C > T) in LOXL1 gene with the risk of primary open-angle glaucoma in a
      Mediterranean population. METHODS: The analysis of genetic polymorphisms was
      performed by standard TaqMan allelic discrimination technique, using a 7900HT
      Sequence Detection System (Applied Biosystems). RESULTS: In a recessive genetic
      model, the T allele of the rs2165241 polymorphism was significantly associated
      with the risk of primary open-angle glaucoma (TT vs. CC: odds ratios = 2.19, 95%
      confidence interval = [1.33-3.62]). After multivariate logistic regression model
      adjusted by age and weight, the magnitude of the association decreased but
      remained statistically significant (TT vs. CC: odds ratios = 2.07, 95% confidence
      interval = [1.20-3.57]). CONCLUSION: This polymorphism seems to be associated
      with high risk for primary open-angle glaucoma in a Mediterranean population.

PMID- 24893573
TI  - Enhanced stability of hippocampal place representation caused by reduced
      magnesium block of NMDA receptors in the dentate gyrus.
AB  - BACKGROUND: Voltage-dependent block of the NMDA receptor by Mg2+ is thought to be
      central to the unique involvement of this receptor in higher brain functions.
      However, the in vivo role of the Mg2+ block in the mammalian brain has not yet
      been investigated, because brain-wide loss of the Mg2+ block causes perinatal
      lethality. In this study, we used a brain-region specific knock-in mouse
      expressing an NMDA receptor that is defective for the Mg2+ block in order to test
      its role in neural information processing. RESULTS: We devised a method to induce
      a single amino acid substitution (N595Q) in the GluN2A subunit of the NMDA
      receptor, specifically in the hippocampal dentate gyrus in mice. This mutation
      reduced the Mg2+ block at the medial perforant path-granule cell synapse and
      facilitated synaptic potentiation induced by high-frequency stimulation. The
      mutants had more stable hippocampal place fields in the CA1 than the controls
      did, and place representation showed lower sensitivity to visual differences. In
      addition, behavioral tests revealed that the mutants had a spatial working memory
      deficit. CONCLUSIONS: These results suggest that the Mg2+ block in the dentate
      gyrus regulates hippocampal spatial information processing by attenuating
      activity-dependent synaptic potentiation in the dentate gyrus.

PMID- 24893576
TI  - The construction of causal schemes: learning mechanisms at the knowledge level.
AB  - This work uses microgenetic study of classroom learning to illuminate (1) the
      role of pre-instructional student knowledge in the construction of normative
      scientific knowledge, and (2) the learning mechanisms that drive change. Three
      enactments of an instructional sequence designed to lead to a scientific
      understanding of thermal equilibration are used as data sources. Only data from a
      scaffolded student inquiry preceding introduction of a normative model were used.
      Hence, the study involves nearly autonomous student learning. In two classes,
      students developed stable and socially shared explanations ("causal schemes") for
      understanding thermal equilibration. One case resulted in a near-normative
      understanding, while the other resulted in a non-normative "alternative
      conception." The near-normative case seems to be a particularly clear example
      wherein the constructed causal scheme is a composition of previously documented
      naive conceptions. Detailed prior description of these naive elements allows a
      much better than usual view of the corresponding details of change during
      construction of the new scheme. A list of candidate mechanisms that can account
      for observed change is presented. The non-normative construction seems also to be
      a composition, albeit of a different structural form, using a different (although
      similar) set of naive elements. This article provides one of very few high
      resolution process analyses showing the productive use of naive knowledge in
      learning. 

PMID- 24893578
TI  - Graphene levitons and anti-levitons in magnetic fields.
AB  - The leviton is an electron or hole wavepacket that rides the surface of the Fermi
      sea. When a series of Lorentzian or Gaussian time dependent pulses are applied to
      an ultracold system a soliton-like excitation with only one electron and no
      localised hole emerges. Graphene is a unique system where the Fermi surface may
      arise from a Dirac point and therewith the levitons character may display many
      interesting features. For example, the leviton formation may be associated with a
      chiral anomaly, and inside a single potential step an anti-leviton forms. We show
      that the application of weak magnetic fields may switch on and off the leviton
      Klein tunnelling. Also, in a moderate field negative refraction arises along a
      curved trajectory, whereas with a stronger field a new elementary excitation -
      the levity vortex - in the reflected wavefunction occurs. Herein we describe
      these phenomena in detail along with a complete explanation of the transmission
      of graphene levitons at a step potential in terms of the probability densities
      and a series of phase diagrams and the tunnelling times. 

PMID- 24893577
TI  - Expression of E-cadherin and beta-catenin in basaloid and conventional squamous
      cell carcinoma of the oral cavity: are potential prognostic markers?
AB  - BACKGROUND: Basaloid squamous cell carcinoma presents with a preference for the
      head and neck region, and shows a distinct aggressive behavior, with frequent
      local recurrences, regional and distant metastasis. The alterations in the
      cadherin-catenin complex are fundamental requirements for the metastasis process,
      and this is the first study to evaluate the immunostaining of E-cadherin and beta
      catenin in oral basaloid squamous cell carcinoma. METHODS: Seventeen cases of
      this tumor located exclusively in the mouth were compared to 26 cases of poorly
      differentiated squamous cell carcinoma and 28 cases of well to moderately
      differentiated squamous cell carcinoma matched by stage and tumor site. The
      immunostaining of E-cadherin and beta-catenin were evaluated in the three groups
      and compared to their clinicopathological features and prognosis. RESULTS: For
      groups poorly differentiated squamous cell carcinoma and basaloid squamous cell
      carcinoma, reduction or absence of E-cadherin staining was observed in more than
      80.0% of carcinomas, and it was statistically significant compared to well to
      moderately differentiated squamous cell carcinoma (p = .019). A strong expression
      of beta-catenin was observed in 26.9% and 20.8% of well to moderately
      differentiated squamous cell carcinoma and poorly differentiated squamous cell
      carcinoma, respectively, and in 41.2% of basaloid squamous cell carcinoma. The 5
      year and 10-year overall and disease-free survival rates demonstrated no
      significant differences among all three groups. CONCLUSIONS: The clinical and
      biological behavior of three groups of the oral cavity tumors evaluated are
      similar. E-cadherin and beta-catenin immunostaining showed no prognostic value
      for basaloid and conventional squamous cell carcinomas.

PMID- 24893579
TI  - Magnolol inhibits tumor necrosis factor-alpha-induced ICAM-1 expression via
      suppressing NF-kappaB and MAPK signaling pathways in human lung epithelial cells.
AB  - Magnolol is a traditional Chinese medicine from the root and bark of Magnolia
      officinalis. It has long been used to treat anxiety, cough, headache and
      allergies, as well as a variety of inflammations. Lung inflammation is a key
      event in the pathogenesis of asthma and chronic obstructive pulmonary disease.
      The present study sought to examine the effects of magnolol on tumor necrosis
      factor (TNF)-alpha-induced upregulation of intercellular adhesion molecule-1
      (ICAM-1), activation of the nuclear factor (NF)-kappaB and mitogen-activated
      protein kinase (MAPK) signaling pathway in cultured human pulmonary epithelial
      cells, and adhesion of human macrophage-like U937 cells to A549 cells. A549 cells
      were incubated with magnolol at 25 and 50 MUmol/l. Then, 20 ng/ml TNF-alpha was
      used to activate the cells. Magnolol inhibited the growth of human pulmonary
      epithelial A549 cells in a dose- and time-dependent manner. Magnolol suppressed
      the adhesion of U937 cells to TNF-alpha-induced A549 cells. In cultured human
      pulmonary epithelial A549 cells, magnolol decreased TNF-alpha-induced
      upregulation of ICAM-1. Magnolol repressed TNF-alpha-induced activation of NF
      kappaB and mitogen-activated protein kinase (MAPK) signaling pathways in A549
      cells by inhibiting phosphorylation of NF-kappaB, p38, extracellular signal
      regulated kinase (ERK) 1/2, and stress-activated protein kinase (SAPK)/c-Jun N
      terminal kinase (JNK). These findings support the hypothesis that magnolol
      inhibits the inflammatory process in lung epithelial A549 cells by suppressing
      the ICAM-1 and NF-kappaB and MAPK signaling pathways. Taken together, these
      results indicate that magnolol offers significant potential as a therapeutic
      treatment for inflammatory diseases of the lungs including asthma, sepsis, and
      chronic obstructive pulmonary disease.

PMID- 24893580
TI  - Lack of association between TESPA1 gene polymorphisms (rs1801876, rs2171497,
      rs4758994, and rs997173) and ankylosing spondylitis in a Chinese population.
AB  - We investigated whether TESPA1 gene polymorphisms were associated with increased
      risk of developing ankylosing spondylitis (AS). We also studied whether TESPA1
      gene interacts with environmental factors. A total of 494 patients with AS and
      478 matched healthy controls were genotyped for four SNPs (rs1801876, rs2171497,
      rs4758994, and rs997173) in the TESPA1 gene. We found no evidence of association
      between these SNPs and AS susceptibility, and between their haplotypes and the
      disease. But, patients with rs1801876 GA, GG, and AA genotypes had significantly
      different Bath Ankylosing Spondylitis Functional Index (BASFI) scores (p =
      0.023). There were significantly different visual analogue scale (VAS) night pain
      assessment scores (p = 0.040) and BASFI scores (p = 0.023) among different
      genotypes at rs2171497 locus. There were also significantly different chest
      expansion scores (p = 0.042) and Bath Ankylosing Spondylitis Disease Activity
      Index (BASDAI) scores (p = 0.014) among different genotypes at rs997173 locus.
      For multiple testing, Bonferroni correction was performed. After Bonferroni
      correction, clinical characteristics of these three loci showed association
      between different genotype groups. These findings indicated that the TESPA1 gene
      is not involved in AS genetic predisposition in the Han Chinese population;
      however, it may play an important role in the clinical characteristics of AS.

PMID- 24893583
TI  - Improvement happens: impacting health at its roots : an interview with Rishi
      Manchanda.

PMID- 24893582
TI  - Gastrointestinal amyloidosis and multiple myeloma.

PMID- 24893581
TI  - A systematic review of stakeholder engagement in comparative effectiveness and
      patient-centered outcomes research.
AB  - OBJECTIVES: We conducted a review of the peer-reviewed literature since 2003 to
      catalogue reported methods of stakeholder engagement in comparative effectiveness
      research and patient-centered outcomes research. METHODS AND RESULTS: We worked
      with stakeholders before, during and after the review was conducted to: define
      the primary and key research questions; conduct the literature search; screen
      titles, abstracts and articles; abstract data from the articles; and analyze the
      data. The literature search yielded 2,062 abstracts. The review was conducted on
      70 articles that reported on stakeholder engagement in individual research
      projects or programs. FINDINGS: Reports of stakeholder engagement are highly
      variable in content and quality. We found frequent engagement with patients,
      modestly frequent engagement with clinicians, and infrequent engagement with
      stakeholders in other key decision-making groups across the healthcare system.
      Stakeholder engagement was more common in earlier (prioritization) than in later
      (implementation and dissemination) stages of research. The roles and activities
      of stakeholders were highly variable across research and program reports.
      RECOMMENDATIONS: To improve on the quality and content of reporting, we developed
      a 7-Item Stakeholder Engagement Reporting Questionnaire. We recommend three
      directions for future research: 1) descriptive research on stakeholder-engagement
      in research; 2) evaluative research on the impact of stakeholder engagement on
      the relevance, transparency and adoption of research; and 3) development and
      validation of tools that can be used to support stakeholder engagement in future
      work.

PMID- 24893585
TI  - Who is who? Non-invasive methods to individually sex and mark altricial chicks.
AB  - Many experiments require early determination of offspring's sex as well as early
      marking of newborns for individual recognition. According to animal welfare
      guidelines, non-invasive techniques should be preferred whenever applicable. In
      our group, we work on different species of song birds in the lab and in the
      field, and we successfully apply non-invasive methods to sex and individually
      mark chicks. This paper presents a comprehensive non-invasive tool-box. Sexing
      birds prior to the expression of secondary sexual traits requires the collection
      of DNA-bearing material for PCR. We established a quick and easy method to sex
      birds of any age (post hatching) by extracting DNA from buccal swabs. Results can
      be obtained within 3 hours. For individual marking chick's down feathers are
      trimmed in specific patterns allowing fast identification within the hatching
      order. This set of methods is easily applicable in a standard equipped lab and
      especially suitable for working in the field as no special equipment is required
      for sampling and storage. Handling of chicks is minimized and marking and sexing
      techniques are non-invasive thereby supporting the RRR-principle of animal
      welfare guidelines. 

PMID- 24893586
TI  - Irrelevant stimuli and action control: analyzing the influence of ignored stimuli
      via the distractor-response binding paradigm.
AB  - Selection tasks in which simple stimuli (e.g. letters) are presented and a target
      stimulus has to be selected against one or more distractor stimuli are frequently
      used in the research on human action control. One important question in these
      settings is how distractor stimuli, competing with the target stimulus for a
      response, influence actions. The distractor-response binding paradigm can be used
      to investigate this influence. It is particular useful to separately analyze
      response retrieval and distractor inhibition effects. Computer-based experiments
      are used to collect the data (reaction times and error rates). In a number of
      sequentially presented pairs of stimulus arrays (prime-probe design),
      participants respond to targets while ignoring distractor stimuli. Importantly,
      the factors response relation in the arrays of each pair (repetition vs. change)
      and distractor relation (repetition vs. change) are varied orthogonally. The
      repetition of the same distractor then has a different effect depending on
      response relation (repetition vs. change) between arrays. This result pattern can
      be explained by response retrieval due to distractor repetition. In addition,
      distractor inhibition effects are indicated by a general advantage due to
      distractor repetition. The described paradigm has proven useful to determine
      relevant parameters for response retrieval effects on human action. 

PMID- 24893587
TI  - Genomic V exons from whole genome shotgun data in reptiles.
AB  - Reptiles and mammals diverged over 300 million years ago, creating two parallel
      evolutionary lineages amongst terrestrial vertebrates. In reptiles, two main
      evolutionary lines emerged: one gave rise to Squamata, while the other gave rise
      to Testudines, Crocodylia, and Aves. In this study, we determined the genomic
      variable (V) exons from whole genome shotgun sequencing (WGS) data in reptiles
      corresponding to the three main immunoglobulin (IG) loci and the four main T cell
      receptor (TR) loci. We show that Squamata lack the TRG and TRD genes, and snakes
      lack the IGKV genes. In representative species of Testudines and Crocodylia, the
      seven major IG and TR loci are maintained. As in mammals, genes of the IG loci
      can be grouped into well-defined IMGT clans through a multi-species phylogenetic
      analysis. We show that the reptilian IGHV and IGLV genes are distributed amongst
      the established mammalian clans, while their IGKV genes are found within a single
      clan, nearly exclusive from the mammalian sequences. The reptilian and mammalian
      TRAV genes cluster into six common evolutionary clades (since IMGT clans have not
      been defined for TR). In contrast, the reptilian TRBV genes cluster into three
      clades, which have few mammalian members. In this locus, the V exon sequences
      from mammals appear to have undergone different evolutionary diversification
      processes that occurred outside these shared reptilian clans. These sequences can
      be obtained in a freely available public repository (http://vgenerepertoire.org).

PMID- 24893584
TI  - Association of living alone and hospitalization among community-dwelling elders
      with and without dementia.
AB  - BACKGROUND: Older persons account for the majority of hospitalizations in the
      United States.1 Identifying risk factors for hospitalization among elders,
      especially potentially preventable hospitalization, may suggest opportunities to
      improve primary care. Certain factors-for example, living alone-may increase the
      risk for hospitalization, and their effect may be greater among persons with
      dementia and the old-old (aged 85+). OBJECTIVES: To determine the association of
      living alone and risk for hospitalization, and see if the observed effect is
      greater among persons with dementia or the old-old. DESIGN: Retrospective
      longitudinal cohort study. PARTICIPANTS: 2,636 participants in the Adult Changes
      in Thought (ACT) study, a longitudinal cohort study of dementia incidence.
      Participants were adults aged 65+ enrolled in an integrated health care system
      who completed biennial follow-up visits to assess for dementia and living
      situation. MAIN MEASURES: Hospitalization for all causes and for ambulatory care
      sensitive conditions (ACSCs) were identified using automated data. KEY RESULTS:
      At baseline, the mean age of participants was 75.5 years, 59 % were female and 36
      % lived alone. Follow-up time averaged 8.4 years (SD 3.5), yielding 10,431
      approximately 2-year periods for analysis. Living alone was positively associated
      with being aged 85+, female, and having lower reported social support and better
      physical function, and negatively associated with having dementia. In a
      regression model adjusted for age, sex, comorbidity burden, physical function and
      length of follow-up, living alone was not associated with all-cause (OR = 0.93;
      95 % CI 0.84, 1.03) or ambulatory care sensitive condition (ACSC) hospitalization
      (OR = 0.88; 95 % CI 0.73, 1.07). Among participants aged 85+, living alone was
      associated with a lower risk for all-cause (OR = 0.76; 95 % CI 0.61, 0.94), but
      not ACSC hospitalization. Dementia did not modify any observed associations.
      CONCLUSION: Living alone in later life did not increase hospitalization risk, and
      in this population may be a marker of healthy aging in the old-old.

PMID- 24893588
TI  - Improved cryopreservation of oil palm (Elaeis guineensis Jacq.) polyembryoids
      using droplet vitrification approach and assessment of genetic fidelity.
AB  - In the present study, polyembryoids of oil palm (Elaeis guineensis Jacq.) were
      cryopreserved with successful revival of 68 % for the first time using the
      droplet vitrification technique. Excised polyembryoids (3-5-mm diameter) from 3
      month-old in vitro cultures were pre-cultured for 12 h in liquid Murashige and
      Skoog medium supplemented with 0.5 M sucrose. The polyembryoids were
      osmoprotected in loading solution [10% (w/v) dimethyl sulphoxide (DMSO) plus 0.7
      M sucrose] for 30 min at room temperature and then placed on aluminium strips
      where they were individually drenched in chilled droplets of vitrification
      solution (PVS2) [30% (w/v) glycerol plus 15% (w/v) ethylene glycol (EG) plus 15%
      (w/v) DMSO plus 0.4 M sucrose] for 10 min. The aluminium strips were enclosed in
      cryovials which were then plunged quickly into liquid nitrogen and kept there for
      1 h. The polyembryoids were then thawed and unloaded (using 1.2 M sucrose
      solution) with subsequent transfer to regeneration medium and stored in zero
      irradiance. Following for 10 days of storage, polyembryoids were cultured under
      16 h photoperiod of 50 MUmol m(-2) s(-1) photosynthetic photon flux density, at
      23 +/- 1  degrees C. Post-thaw growth recovery of 68% was recorded within 2 weeks
      of culture, and new shoot development was observed at 4 weeks of growth. Scanning
      electron microscopy revealed that successful regeneration of cryopreserved
      polyembryoids was related to maintenance of cellular integrity, presumably
      through PVS2 exposure for 10 min. The present study demonstrated that
      cryopreservation by droplet vitrification enhanced the regeneration percentages
      of oil palm in comparison with the conventional vitrification method previously
      reported.

PMID- 24893589
TI  - Anatomical and ultrastructural adaptations of seagrass leaves: an evaluation of
      the southern Atlantic groups.
AB  - Seagrasses, which form an integral part of the worldwide coastal habitat, are
      considered highly relevant from an ecological point of view. Due to the scarcity
      of anatomical information, the present study analyzed the morphoanatomy,
      histochemistry, and ultrastructure of Halophila decipiens, Halodule wrightii, and
      Ruppia maritima leaves, discussing their adaptations to the marine environments
      observed throughout the southwestern tropical and subtropical Atlantic coast. The
      leaves of these three species feature a uniseriate epidermis with the presence of
      chloroplasts in large quantities and absence of stomata. The vascular system
      consists of a central vascular bundle with sieve tube elements of the phloem and
      protoxylem lacunae, as well as small vascular bundles near the leaf margins. The
      leaves of H. decipiens possess trichomes, but no mesophyll in the leaf margins.
      The mesophyll of H. wrightii and R. maritima is homogeneous with chlorenchyma
      cells and air lacunae scattered throughout the leaf. The histochemistry analysis
      revealed the absence of amyloplasts and the presence of proteins in the outer
      periclinal walls of ordinary epidermal cells of the three species. It was also
      possible to detect the presence of idioblasts containing phenolic compounds in H.
      decipiens and R. maritima. The ultrastructural analysis of the three species
      revealed many elliptical chloroplasts, with organized thylakoids, expansion of
      the epidermal cell wall into the cytoplasm, and a thin cuticle. Hydropoten were
      also observed in the three specimens. The results show that the species analyzed
      have important adaptations which enable their survival in the marine environment.

PMID- 24893590
TI  - Progressive myoclonus epilepsy in Down syndrome patients with dementia.
AB  - This study aimed to elucidate the natural history of senile myoclonic epilepsy, a
      type of myoclonic epilepsy associated with Alzheimer's disease in adult Down
      syndrome patients. Twelve Down syndrome patients over the age of 40 years with
      myoclonic epilepsy and Alzheimer's disease underwent clinical,
      neuropsychological, neurophysiological, and neuroradiological study. The
      kariotypes, APOE polymorphisms, all exons in the PSEN1 and PSEN2 genes, and exons
      16 and 17 in the APP gene were determined for all patients. CSF Abeta42, p
      tau181, and t-tauAg were determined for two patients. Three main stages appeared
      during the course of the syndrome. The first stage was characterized by dementia
      onset (mean age: 51 +/- 6.6 years), diffuse EEG abnormalities during sleep, and
      cerebral atrophy determined using neuroimaging. During the second stage,
      myoclonic epilepsy manifested (mean age: 51.4 +/- 7.2 years) with myoclonic jerks
      time-locked to diffuse epileptiform abnormalities upon awakening, which was
      controlled with antiepileptic drugs. During the third stage (mean age: 54.8 +/-
      7.6 years), myoclonic seizures were replaced with nonepileptic myoclonus, and
      cerebellar signs, severe dementia, and photosensitivity developed. All patients
      showed complete trisomy 21. Mutations were ruled out on the APP, PSEN1, and PSEN2
      genes, and APOE analysis revealed epsilon3/epsilon3 homozygosity. CSF biomarkers
      showed a decrease in Abeta42 and an increase in p-tau181. The natural history of
      senile myoclonic epilepsy is consistent with progressive myoclonus epilepsy.
      Chromosome 21 is implicated in its pathophysiology; however, other genetic and/or
      environmental risk factors cannot be excluded. The absence of the APOE type 4
      allele could predict its progression.

PMID- 24893591
TI  - Measuring disease progression in corticobasal syndrome.
AB  - Corticobasal syndrome (CBS) is a complex neurodegenerative disorder with marked
      clinical, neuropsychological, and pathological heterogeneity. Measurement of
      disease progression in CBS is complex and little understood. This study aimed to
      establish clinical and neuropsychological indicators of prognosis in CBS.
      Patients with CBS were retrospectively recruited from a frontotemporal dementia
      specific research clinic. All patients underwent detailed clinical and
      neuropsychological testing including the frontotemporal dementia rating scale
      (FRS). Using the differences in FRS logit scores over a period of 12 months, CBS
      patients were divided into rapid and slow progressor groups. Demographic,
      clinical and neuropsychological features were compared between the two groups.
      Sixteen participants who met defined criteria were included (9 males, 7 females;
      mean age 65.8 +/- 22 years; median symptom duration 51.8 +/- 22 years; mean
      duration of follow-up 11.4 +/- 2.8 months). There were no significant differences
      between the rapid and slow progressors in age, gender, symptom duration,
      motor/cognitive presentation, and ACE-R scores at baseline. Clinically, slow
      progressors were significantly more likely to have a motor speech disorder, with
      a trend for more frequent dysgraphia, whereas rapid progressors were more likely
      to exhibit surface dyslexia. Rapid and slow progressor groups did not differ on
      neuropsychological performance. The presence of motor speech disorder,
      dysgraphia, and surface dyslexia may be useful in differentiating patients with
      rapid progression of CBS from those with a more indolent disease course.

PMID- 24893592
TI  - Diagnosis of neoplasia in Barrett's esophagus using vital-dye enhanced
      fluorescence imaging.
AB  - The ability to differentiate benign metaplasia in Barrett's Esophagus (BE) from
      neoplasia in vivo remains difficult as both tissue types can be flat and
      indistinguishable with white light imaging alone. As a result, a modality that
      highlights glandular architecture would be useful to discriminate neoplasia from
      benign epithelium in the distal esophagus. VFI is a novel technique that uses an
      exogenous topical fluorescent contrast agent to delineate high grade dysplasia
      and cancer from benign epithelium. Specifically, the fluorescent images provide
      spatial resolution of 50 to 100 MUm and a field of view up to 2.5 cm, allowing
      endoscopists to visualize glandular morphology. Upon excitation, classic
      Barrett's metaplasia appears as continuous, evenly-spaced glands and an overall
      homogenous morphology; in contrast, neoplastic tissue appears crowded with
      complete obliteration of the glandular framework. Here we provide an overview of
      the instrumentation and enumerate the protocol of this new technique. While VFI
      affords a gastroenterologist with the glandular architecture of suspicious
      tissue, cellular dysplasia cannot be resolved with this modality. As such, one
      cannot morphologically distinguish Barrett's metaplasia from BE with Low-Grade
      Dysplasia via this imaging modality. By trading off a decrease in resolution with
      a greater field of view, this imaging system can be used at the very least as a
      red-flag imaging device to target and biopsy suspicious lesions; yet, if the
      accuracy measures are promising, VFI may become the standard imaging technique
      for the diagnosis of neoplasia (defined as either high grade dysplasia or cancer)
      in the distal esophagus.

PMID- 24893593
TI  - Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the
      molecular basis of antimalarial drug action.
AB  - Atovaquone, a substituted hydroxynaphthoquinone, is a potent antimalarial drug
      that acts by inhibiting the parasite's mitochondrial cytochrome bc1 complex (cyt
      bc1). Mutations in cyt bc1 confer atovaquone resistance. Here we describe the X
      ray structure of mitochondrial cyt bc1 from Saccharomyces cerevisiae with
      atovaquone bound in the catalytic Qo site, at 3.0-A resolution. A polarized H
      bond to His181 of the Rieske protein in cyt bc1 traps the ionized hydroxyl group
      of the drug. Side chains of highly conserved cytochrome b residues establish
      multiple non-polar interactions with the napththoquinone group, whereas less
      conserved residues are in contact with atovaquone's cyclohexyl-chlorophenyl tail.
      Our structural analysis reveals the molecular basis of atovaquone's broad target
      spectrum, species-specific efficacies and acquired resistances, and may aid drug
      development to control the spread of resistant parasites. 

PMID- 24893594
TI  - Radical phosphinylation of alpha,alpha-diaryl allylic alcohols with concomitant
      1,2-aryl migration.
AB  - A novel radical phosphinylation of alpha,alpha-diaryl allylic alcohols with
      arylphosphine oxides was described for the direct preparation of alpha-aryl-beta
      phosphinylated carbonyl ketones in medium to good yields via 1,2-aryl migration.
      In this reaction, formation of new C(Ar)-C(sp(3)) and C(sp(3))-P bonds was
      observed. 

PMID- 24893596
TI  - Immunological analyses of whole blood via "microfluidic drifting" based flow
      cytometric chip.
AB  - Cost-effective, high-performance diagnostic instruments are vital to providing
      the society with accessible, affordable, and high-quality healthcare. Here we
      present an integrated, "microfluidic drifting" based flow cytometry chip as a
      potential inexpensive, fast, and reliable diagnostic tool. It is capable of
      analyzing human blood for cell counting and diagnosis of diseases. Our device
      achieves a throughput of ~3754 events/s. Calibration with Flow-Check calibration
      beads indicated good congruency with a commercially available benchtop flow
      cytometer. Moreover, subjection to a stringent 8-peak rainbow calibration
      particle test demonstrated its ability to perform high-resolution immunological
      studies with separation resolution of 4.28 between the two dimmest fluorescent
      populations. Counting accuracy at different polystyrene bead concentrations
      showed strong correlation (r=0.9991) with hemocytometer results. Finally,
      reliable quantification of CD4+ cells in healthy human blood via staining with
      monoclonal antibodies was demonstrated. These results demonstrate the potential
      of our microfluidic flow cytometry chip as an inexpensive yet high-performance
      point-of-care device for mobile medicine.

PMID- 24893595
TI  - Ridge preservation for implant therapy: a review of the literature.
AB  - Healing of the extraction socket after tooth removal involves retention of the
      blood clot followed by a sequence of events that lead to changes in the alveolar
      process in a three dimensional fashion. This normal healing event results in a
      minimal loss of vertical height (around 1 mm), but a substantial loss of width in
      the buccal-lingual plane (4-6 mm). During the first three months following
      extraction that loss has been shown to be significant and may result in both a
      hard tissue and soft tissue deformity affecting the ability to restore the site
      with acceptable esthetics. Procedures that reduce the resorptive process have
      been shown to be predictable and potentially capable of eliminating secondary
      surgery for site preparation when implant therapy is planned. The key element is
      prior planning by the dental therapist to act at the time of extraction to
      prevent the collapse of the ridge due to the loss of the alveolus. Several
      techniques have been employed as ridge preservation procedures involving the use
      of bone grafts, barrier membranes and biologics to provide a better restorative
      outcome. This review will explore the evidence behind each technique and their
      efficacy in accomplishing site preparation. The literature does not identify a
      single technique as superior to others; however, all accepted therapeutic
      procedures for ridge preservation have been shown to be more effective than blood
      clot alone in randomized controlled studies. 

PMID- 24893597
TI  - Prediction of three dimensional maximum isometric neck strength.
AB  - We measured maximum isometric neck strength under combinations of
      flexion/extension, lateral bending and axial rotation to determine whether neck
      strength in three dimensions (3D) can be predicted from principal axes strength.
      This would allow biomechanical modelers to validate their neck models across many
      directions using only principal axis strength data. Maximum isometric neck
      moments were measured in 9 male volunteers (29+/-9 years) for 17 directions. The
      3D moments were normalized by the principal axis moments, and compared to unity
      for all directions tested. Finally, each subject's maximum principal axis moments
      were used to predict their resultant moment in the off-axis directions. Maximum
      moments were 30+/-6 N m in flexion, 32+/-9 N m in lateral bending, 51+/-11 N m in
      extension, and 13+/-5 N m in axial rotation. The normalized 3D moments were not
      significantly different from unity (95% confidence interval contained one),
      except for three directions that combined ipsilateral axial rotation and lateral
      bending; in these directions the normalized moments exceeded one. Predicted
      resultant moments compared well to the actual measured values (r2=0.88). Despite
      exceeding unity, the normalized moments were consistent across subjects to allow
      prediction of maximum 3D neck strength using principal axes neck strength.

PMID- 24893598
TI  - Ginsenoside Rh2 alleviates dextran sulfate sodium-induced colitis via augmenting
      TGFbeta signaling.
AB  - Ginsenoside Rh2 (GRh2) has been reported to have therapeutic effects on various
      diseases. However, whether it may also affect the recovery from ulcerative
      colitis remains unknown. Here we induced colitis in mice by dextran sulfate
      sodium (DSS) administration, and then treated the mice with GRh2. We found that
      GRh2-treated mice showed significant alleviation of the DSS-induced colitis.
      Moreover, significant increase in the activity of TGFbeta signaling was detected
      in the GRh2-treated colon that had received DSS. To investigate whether there is
      a causative link among GRh2 treatment, TGFbeta signaling augment and the cure of
      colitis, we gave the DSS-treated mice a combination of GRh2 and a specific
      TGFbeta receptor I inhibitor, SB431542. SB431542 significantly decreased the
      activation of TGFbeta signaling in the colon from the GRh2-administrated mice,
      and consequently attenuated the therapeutic effect of GRh2. Our data thus
      demonstrate that GRh2 may alleviate DSS-induced colitis via augmenting TGFbeta
      signaling. 

PMID- 24893599
TI  - Exploring genetic variability within lentil (Lens culinaris Medik.) and across
      related legumes using a newly developed set of microsatellite markers.
AB  - Lentil (Lens culinaris Medik.) is an economically important grain legume, yet the
      genetic and genomic resources remain largely uncharacterized and unexploited in
      this crop. Microsatellites have become markers of choice for crop improvement
      applications. Hence, simple sequence repeat (SSR) markers were developed for
      lentil through the construction of genomic library enriched for GA/CT motifs. As
      a result 122 functional SSR primer pairs were developed from 151 microsatellite
      loci and validated in L. culinaris cv. Precoz. Thirty three SSR markers were
      utilized for the analysis of genetic relationships between cultivated and wild
      species of Lens and related legumes. A total of 123 alleles were amplified at 33
      loci ranging from 2-5 alleles with an average of 3.73 alleles per locus.
      Polymorphic information content (PIC) for all the loci ranged from 0.13 to 0.99
      with an average of 0.66 per locus. Varied levels of cross genera transferability
      were obtained ranging from 69.70 % across Pisum sativum to 12.12 % across Vigna
      radiata. The UPGMA based dendrogram was able to establish the uniqueness of each
      genotype and grouped them into two major clusters clearly resolving the genetic
      relationships within lentil and related species. The new set of SSR markers
      reported here were efficient and highly polymorphic and would add to the existing
      repertoire of lentil SSR markers to be utilized in molecular breeding. Moreover,
      the improved knowledge about intra- and inter-specific genetic relationships
      would facilitate germplasm utilization for lentil improvement.

PMID- 24893600
TI  - Anthocyanin biosynthetic genes in Brassica rapa.
AB  - BACKGROUND: Anthocyanins are a group of flavonoid compounds. As a group of
      important secondary metabolites, they perform several key biological functions in
      plants. Anthocyanins also play beneficial health roles as potentially protective
      factors against cancer and heart disease. To elucidate the anthocyanin
      biosynthetic pathway in Brassica rapa, we conducted comparative genomic analyses
      between Arabidopsis thaliana and B. rapa on a genome-wide level. RESULTS: In
      total, we identified 73 genes in B. rapa as orthologs of 41 anthocyanin
      biosynthetic genes in A. thaliana. In B. rapa, the anthocyanin biosynthetic genes
      (ABGs) have expanded and most genes exist in more than one copy. The anthocyanin
      biosynthetic structural genes have expanded through whole genome and tandem
      duplication in B. rapa. More structural genes located upstream of the anthocyanin
      biosynthetic pathway have been retained than downstream. More negative regulatory
      genes are retained in the anthocyanin biosynthesis regulatory system of B. rapa.
      CONCLUSIONS: These results will promote an understanding of the genetic mechanism
      of anthocyanin biosynthesis, as well as help the improvement of the nutritional
      quality of B. rapa through the breeding of high anthocyanin content varieties.

PMID- 24893601
TI  - Antioxidant, total phenolic contents and antinociceptive potential of Teucrium
      stocksianum methanolic extract in different animal models.
AB  - BACKGROUND: Oxidative stress and analgesia are connected with different
      pathological conditions. The drug candidates from synthetic sources are
      associated with various side effects; therefore, researchers are giving priority
      to find novel, effective and safe phytomedicines. Teucrium species possesses
      antioxidant, analgesic, anti-inflammatory and hepatoprotective activities. The
      essential oils of Teucrium stocksianum have shown strong antinociceptive
      potential. Our current study is designed to embark total phenolic content (TPC),
      antioxidant and antinociceptive potential of the methanolic extract of Teucrium
      stocksianum (METS). METHOD: Phytochemical composition was determined by using
      standard methods. Free radical scavenging potential and TPC of METS were assessed
      by using 2, 2-diphenyl-1-picryl-hydrazyl (DPPH) and Folin-Ciocalteu Reagent (FCR)
      respectively. Antinociceptive potential was determined by acetic acid induced
      abdominal writhing, formalin induced paw licking and tail immersion tests.
      Different test dose 50, 100 and 150 mg/kg body weight of METS were administered
      intra peritonealy (i.p) to various groups of mice for the evaluation of analgesic
      potential. RESULTS: Phytochemical screening confirmed the presence of flavonoids,
      tannins, saponins, anthraquinone, steroid, phlobatannin, terpenoid, glycoside and
      reducing sugars. METS was found safe at a dose of 1000 mg/kg body weight. A
      concentration dependent free radical scavenging effect was observed with
      methanolic aerial parts extract of Teucrium stocksianum (MAPETS) and methanolic
      roots extracts of Teucrium stocksianum (MRETS). MAPETS and MRETS have shown
      highest antioxidant activity 91.72% and 86.19% respectively at 100 MUg/ml. MAPETS
      was found more rich (115.32 mg of GAE/g of dry material) in TPC as compared to
      MAPETS (105.41 mg of GAE/g). METS demonstrated a dose dependent antinociceptive
      potential in different pain models, like in acetic acid, formalin and tail
      immersion showing 83.103%, 80.872% and 67.58% at a dose of 150 mg/kg, similar to
      acetylsalicylic acid (74.79%, 82.87%, 100 mg/kg) and TramadolR (74%, 30 mg/kg)
      respectively. CONCLUSION: Strong antioxidant potential and high TPCs are residing
      in the methanolic extract of T. stocksianum. METS showed analgesic potential in
      all models of nociception implying that both peripheral and central pathways of
      analgesia are involved. This might be due to the presence of various classes of
      phytochemicals in the plant extract.

PMID- 24893602
TI  - Predicting quit attempts among homeless smokers seeking cessation treatment: an
      ecological momentary assessment study.
AB  - INTRODUCTION: Homeless adults are more likely to smoke tobacco and are less
      likely to successfully quit smoking than smokers in the general population,
      despite comparable numbers of cessation attempts and desire to quit. To date,
      studies that have examined smoking cessation in homeless samples have used
      traditional lab/clinic-based assessment methodologies. Real-time assessment of
      key variables may provide new insights into the process of quitting among
      homeless smokers. METHODS: The purpose of the current study was to identify
      predictors of a quit attempt using real-time assessment methodology during the 6
      days prior to a scheduled quit attempt among homeless adults seeking care at a
      shelter-based smoking cessation clinic. Parameters for multiple variables (i.e.,
      motivation for quitting, smoking expectancies, quit self-efficacy, smoking urges,
      negative affect, positive affect, restlessness, hostility, and stress) were
      calculated and were used as predictors of biochemically verified quit date
      abstinence (i.e., >=13hr abstinent) using logistic regression analyses. RESULTS:
      Participants (n = 57) were predominantly male (59.6%), non-White (68.4%), and
      smoked an average of 18 cigarettes per day. A total of 1,132 ecological momentary
      assessments (83% completion rate) were collected at random times (i.e., up to 4
      assessments/day) during the 6 days prior to a scheduled quit attempt. Results
      indicated that declining (negative slope) negative affect, restlessness, and
      stress predicted quit date abstinence. Additionally, increasing positive coping
      expectancies across the prequit week predicted quit date abstinence. CONCLUSIONS:
      Study findings highlight multiple variables that may be targeted during the
      precessation period to increase smoking cessation attempts in this difficult to
      treat population of smokers.

PMID- 24893603
TI  - Herbal medicines for cancer cachexia: protocol for a systematic review.
AB  - INTRODUCTION: To assess the efficacy of herbal medicines as a treatment of cancer
      cachexia. METHODS AND ANALYSIS: We will search the following 13 electronic
      databases from their inception. MEDLINE (PubMed), the Cochrane Central Register
      of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine
      Database (AMED), China National Knowledge Infrastructure (CNKI), Wanfang, Journal
      Integration Platform (VIP) and six Korean Medical Databases (KoreaMed, the Korean
      Traditional knowledge Portal, OASIS, DBPIA, the Research Information Service
      System and the Korean Studies Information Service System) without restrictions on
      time or language. The data will be extracted independently by two authors using
      predefined criteria. Disagreements will be resolved by discussion between the
      authors. The risk of bias will be assessed using the Cochrane risk of bias tool.
      DISSEMINATION: The review will be published in a journal. The review will also be
      disseminated electronically and in print. An update of the review will be
      conducted to inform and guide healthcare practice and policy. TRIAL REGISTRATION
      NUMBER: PROSPERO 2013:CRD42013006612.

PMID- 24893604
TI  - Awareness and treatment of alcohol dependence in Japan: results from internet
      based surveys in persons, family, physicians and society.
AB  - AIMS: To understand current awareness of, and views on, treatment of alcohol
      dependence in Japan. METHODS: (a) Nationwide internet-based survey of 520
      individuals, consisting of 52 diagnosed alcohol-dependent (AD) persons, 154
      potentially alcohol-dependent (ADP) persons, 104 family members and 106
      friends/colleagues of AD persons, and 104 general individuals, derived from a
      consumer panel where the response rate was 64.3%. We enquired into awareness
      about the treatment of alcohol dependence and patient pathways through the
      healthcare network. (b) Nationwide internet-based survey of physicians (response
      rate 10.1% (2395/23,695) to ask 200 physicians about their management of alcohol
      use disorders). RESULTS: We deduced that 10% of alcohol-dependent Japanese
      persons had ever been diagnosed with alcohol dependence, with only 3% ever
      treated. Regarding putative treatment goals, 20-25% of the AD and ADP persons
      would prefer to attempt to abstain, while 60-75% preferred 'reduced drinking.' A
      half of the responding physicians considered abstinence as the primary treatment
      goal in alcohol dependence, while 76% considered reduced drinking as an
      acceptable goal. CONCLUSION: AD and ADP persons in Japan have low 'disease
      awareness' defined as 'understanding of signs, symptoms and consequences of
      alcohol use disorders,' which is in line with the overseas situation. The
      Japanese drinking culture and stigma toward alcohol dependence may contribute to
      such low disease awareness and current challenging treatment environment. While
      abstinence remains the preferred treatment goal among physicians, reduced
      drinking seems to be an acceptable alternative treatment goal to many persons and
      physicians in Japan.

PMID- 24893605
TI  - Improving dementia health literacy using the FLOW mnemonic: pilot findings from
      the Old SCHOOL hip-hop program.
AB  - BACKGROUND: Dementia health literacy is low among the public and likely poses a
      significant barrier to Alzheimer's disease (AD) symptom recognition and
      treatment, particularly among minority populations already facing higher AD
      burden. We evaluated the pilot phase of a novel AD health education program, Old
      SCHOOL (Seniors Can Have Optimal Aging and Ongoing Longevity) Hip-Hop (OSHH),
      which is designed to enable children to be AD health educational conduits in the
      home ("child-mediated health communication"). METHOD: OSHH applied our stroke
      validated model of engaging, dynamic, and age- and culturally appropriate
      curriculum delivered to elementary school-age children (fourth/fifth grades, ages
      9-11 years). We assessed AD knowledge among the children at baseline, immediately
      following the intervention (1-hour program delivered daily over 3 consecutive
      days), and 3 months later. For key AD symptoms, we developed the FLOW mnemonic
      (forget, lose, overlook, write/wander); students were additionally taught action
      plans for recognized symptoms. RESULTS: Seventy-five students completed baseline
      assessments, and 68 completed posttesting. AD symptoms in FLOW were not well
      known at baseline (individually ranging from 16% to 71% correct) but were highly
      learned after 3 days (89% to 98% correct) and retained well after 3 months (80%
      to 95% correct, p <= .01 for all comparisons vs. baseline). AD localization,
      including its effect on memory and the hippocampus, was also highly learned and
      retained (p < .001). Eighteen students (24%) reported having a close
      friend/family member with AD. CONCLUSIONS: This study suggests our hip-hop health
      education model may be an effective method to improve AD health literacy.

PMID- 24893606
TI  - Colonic stenosis caused by infection of an intraperitoneal access port system: a
      rare complication of intraperitoneal chemotherapy for gastric cancer with
      peritoneal metastasis.
AB  - BACKGROUND: Intraperitoneal (i.p.) chemotherapy is garnering attention as an
      effective treatment for gastric cancer with peritoneal metastasis. We report the
      case of a patient who developed colonic stenosis caused by infection of an i.p.
      access port system during i.p. chemotherapy. It was difficult to differentiate
      whether the extrinsic colonic stenosis arose from a catheter infection or
      peritoneal metastasis of the gastric cancer. CASE PRESENTATION: A 66-year-old
      Japanese man underwent total gastrectomy for gastric cancer. Because the
      intraoperative findings revealed peritoneal metastasis, a port system was
      implanted for subsequent i.p. chemotherapy. Two months after initiation of
      chemotherapy, he complained of vomiting and abdominal pain. A computed tomography
      scan revealed marked thickening of the sigmoid colon wall adjacent to the
      catheter of the i.p. access port system. A barium enema demonstrated extrinsic
      irregular stenosis of the sigmoid colon. Although it was difficult to distinguish
      whether infection or peritoneal metastasis had caused the colonic stenosis, we
      removed the port system to obtain a therapeutic diagnosis. Coagulase-negative
      staphylococci were detected by catheter culture. The wall thickening and stenosis
      of the sigmoid colon completely resolved after removal of the port system.
      CONCLUSIONS: We report the case of a rare complication in association with an
      i.p. access port system. Infection of the port system should be considered as a
      differential diagnosis when colonic stenosis adjacent to the catheter is observed
      during i.p. chemotherapy.

PMID- 24893609
TI  - Radiation oncology: a perspective on health reform and value-based initiatives.

PMID- 24893607
TI  - Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men
      from Europe and the USA.
AB  - STUDY QUESTION: Is there an association between alcohol intake and semen quality
      and serum reproductive hormones among healthy men from the USA and Europe?
      SUMMARY ANSWER: Moderate alcohol intake is not adversely associated with semen
      quality in healthy men, whereas it was associated with higher serum testosterone
      levels. WHAT IS KNOWN ALREADY: High alcohol intake has been associated with a
      wide range of diseases. However, few studies have examined the correlation
      between alcohol and reproductive function and most have been conducted in
      selected populations of infertile men or have a small sample size and the results
      have been contradictory. STUDY DESIGN, SIZE, DURATION: A coordinated
      international cross-sectional study among 8344 healthy men. A total of 1872
      fertile men aged 18-45 years (with pregnant partners) from four European cities
      and four US states, and 6472 young men (most with unknown fertility) aged 18-28
      years from the general population in six European countries were recruited.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The men were recruited using
      standardized protocols. A semen analysis was performed and men completed a
      questionnaire on health and lifestyle, including their intake of beer, wine and
      liquor during the week prior to their visit. Semen quality (semen volume, sperm
      concentration, percentage motile and morphologically normal sperm) and serum
      reproductive hormones (FSH, LH, testosterone, sex hormone-binding globulin, and
      inhibin B and free testosterone) were examined. MAIN RESULTS AND THE ROLE OF
      CHANCE: The participation rate for our populations was 20-30%. We found no
      consistent association between any semen variable and alcohol consumption, which
      was low/moderate in this group (median weekly intake 8 units), either for total
      consumption or consumption by type of alcohol. However, we found a linear
      association between total alcohol consumption and total or free testosterone in
      both groups of men. Young and fertile men who consumed >20 units of alcohol per
      week had, respectively, 24.6 pmol/l (95% confidence interval 16.3-32.9) and 19.7
      pmol/l (7.1-32.2) higher free testosterone than men with a weekly intake between
      1 and 10 units. Alcohol intake was not significantly associated with serum
      inhibin B, FSH or LH levels in either group of men. The study is the largest of
      its kind and has sufficient power to detect changes in semen quality and
      reproductive hormones. LIMITATIONS, REASONS FOR CAUTION: The participation rate
      was low, but higher than in most previous semen quality studies. In addition, the
      study was cross-sectional and the men were asked to recall their alcohol intake
      in the previous week, which was used as a marker of intake up to 3 months before.
      If consumption in that week differed from the typical weekly intake and the
      intake 3 months earlier, misclassification of exposure may have occurred.
      However, the men were unaware of their semen quality when they responded to the
      questions about alcohol intake. Furthermore, we cannot exclude that our findings
      are due to unmeasured confounders, including diet, exercise, stress, occupation
      and risk-taking behavior. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests
      that moderate alcohol intake is not adversely associated with semen quality in
      healthy men, whereas it was associated with higher serum testosterone levels
      which may be due to a changed metabolism of testosterone in the liver. Healthy
      men may therefore be advised that occasional moderate alcohol intake may not harm
      their reproductive health; we cannot address the risk of high alcohol consumption
      of longer duration or binge drinking on semen quality and male reproductive
      hormones. STUDY FUNDING/COMPETING INTERESTS: All funding sources were non
      profitable and sponsors of this study played no role in the study design, in data
      collection, analysis, or interpretation, or in the writing of the article. The
      authors have no conflicts of interest.

PMID- 24893610
TI  - Colorectal cancer survivors' needs and preferences for survivorship information.
AB  - PURPOSE: Before developing a survivorship care plan (SCP) that colorectal cancer
      (CRC) survivors will value, understanding the informational needs of CRC
      survivors is critical. METHODS: We surveyed survivors treated for nonmetastatic
      CRC at two hospitals in New York about their needs and preferences for
      survivorship information. Participants completed treatment 6 to 24 months before
      the interview and had not received an SCP. We evaluated whether survivors knew
      their treatment history (10 topics), whether they understood ongoing risks (four
      topics), and their preferences for receiving 16 topics of survivorship
      information. RESULTS: One hundred seventy-five survivors completed the survey.
      Most survivors remembered information about past treatment (98% to 99% for each
      treatment). Fewer survivors knew their risks of local recurrence, distant
      recurrence, or developing a new CRC (69%, 77%, and 40%, respectively). Most
      participants reported receiving information about their cancer history and
      ongoing oncology visits (77% to 86% across topics). Across all topics, 93% to 99%
      of those who reported receiving information found the information useful. A
      minority of survivors reported they received information about symptoms to report
      to doctors, returning to work, or financial or legal issues (5% to 48% across
      topics), but those who did found the information useful (89% to 100% across
      topics). CONCLUSIONS: In the absence of an SCP, CRC survivors still generally
      understood their cancer history. However, many lacked knowledge of ongoing risks
      and prevention. Most survivors stated that they found the survivorship
      information they received useful. SCPs for CRC survivors should focus less on
      past care and more on helping survivors understand their risks and plan for the
      future.

PMID- 24893611
TI  - Acute white matter injury after experimental subarachnoid hemorrhage: potential
      role of lipocalin 2.
AB  - BACKGROUND AND PURPOSE: White matter injury occurs after subarachnoid hemorrhage
      (SAH) and has not been well studied. In this study, we investigated acute white
      matter injury in a mouse SAH model and the role of lipocalin 2 (LCN2) in that
      injury. METHODS: SAH was induced by endovascular perforation in wild-type (WT) or
      LCN2 knockout (LCN2-/-) mice. Sham WT mice underwent the same procedure without
      perforation. MRI was performed 24 hours after SAH and the volumes of the T2
      hyperintensity in white matter were measured. Immunohistochemistry was performed
      to determine white matter injury. RESULTS: Mortality rates and SAH severity were
      not significantly different between WT and LCN2-/- animals. T2-hyperintensity in
      the white matter was observed in all WT animals at 24 hours after SAH (6.1+/-2.7
      versus 0.06+/-0.07 mm3 in sham; P<0.001), and the volume of T2-hyperintensity
      tended to correlate with SAH severity (r=0.30; P=0.055). In WT animals with SAH,
      numerous LCN2-positive cells were observed in white matter. In contrast, LCN2-/-
      animals scarcely developed white matter T2-hyperintensity after SAH (0.5+/-0.5
      mm3; P<0.001, versus WT). Markers of axonal damage and myelin degradation were
      increased in white matter after SAH in WT compared with those in LCN2-/- animals
      (P<0.05). CONCLUSIONS: SAH results in an acute white matter injury at 24 hours in
      mice, and LCN2 plays an important role in SAH-induced white matter injury.

PMID- 24893612
TI  - Impact of prestroke selective serotonin reuptake inhibitor treatment on stroke
      severity and mortality.
AB  - BACKGROUND AND PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) have been
      associated with an increased risk of bleeding but also a possible neuroprotective
      effect in stroke. We aimed to examine the implications of prestroke SSRI use in
      hemorrhagic and ischemic stroke. METHODS: We conducted a registry-based
      propensity score-matched follow-up study among first-ever patients with
      hemorrhage and ischemic stroke in Denmark (2003-2012). Multiple conditional
      logistic regression was used to compute adjusted odds ratios of severe stroke and
      death within 30 days. RESULTS: Among 1252 hemorrhagic strokes (626 prestroke SSRI
      users and 626 propensity score-matched nonusers), prestroke SSRI use was
      associated with an increased risk of the strokes being severe (adjusted
      propensity score-matched odds ratios, 1.41; confidence interval, 1.08-1.84) and
      an increased risk of death within 30 days (adjusted propensity score-matched odds
      ratios, 1.60; confidence interval, 1.17-2.18). Among 8956 patients with ischemic
      stroke (4478 prestroke SSRI users and 4478 propensity score-matched nonusers),
      prestroke SSRI use was not associated with the risk of severe stroke or death
      within 30 days. CONCLUSIONS: Prestroke SSRI use is associated with increased
      stroke severity and mortality in patients with hemorrhagic stroke. Although
      prestroke depression in itself may increase stroke severity and mortality, this
      was not found in SSRI users with ischemic stroke.

PMID- 24893614
TI  - The effect of long-term oral L-carnitine administration on insulin sensitivity,
      glucose disposal, plasma concentrations of leptin and acylcarnitines, and urinary
      acylcarnitine excretion in warmblood horses.
AB  - BACKGROUND: Insulin resistance in horses is an emerging field of interest as it
      is thought to be a contributing factor in the pathogenesis of many equine
      conditions. OBJECTIVES: The objectives of the present study were to determine the
      effects of long-term oral administration of L-carnitine on insulin sensitivity,
      glucose disposal, plasma leptin concentrations and acylcarnitine spectrum both in
      plasma and urine. ANIMALS AND METHODS: Six 3-year-old healthy warmblood geldings
      were used. In a double blind 2 * 2 Latin square design at a dosage of 100 mg/kg
      body weight (BW)/day for 28 days the effects of oral supplementation of L
      carnitine (as fumarate) were assessed. Glucose disposal and insulin sensitivity
      were measured by means of the euglycemic-hyperinsulinemic clamp technique.
      Radioimmunoassays were used to determine plasma leptin and insulin
      concentrations. Electrospray tandem mass spectrometry was used to assess
      acylcarnitines both in plasma and urine. Statistical analysis was performed using
      a linear mixed-effects model and P values <0.05 were considered significant.
      RESULTS: Long-term L-carnitine administration did not affect insulin sensitivity.
      Plasma leptin and free carnitine concentrations in plasma and urine increased
      significantly (P = 0.047 and 0.000, respectively) following L-carnitine
      administration as well as short-chain acylcarnitines in plasma and urinary
      excretion of short- and medium-chain acylcarnitines. CONCLUSION AND CLINICAL
      RELEVANCE: Given the effects of oral administration of L-carnitine further
      clinical study is necessary in order to assess the potential beneficial effects
      in equine patients suffering from metabolic myopathies such as acquired multiple
      acyl-CoA dehydrogenase deficiency. IMPACT FOR HUMAN MEDICINE: The current study
      supports the treatment rationale of short-chain acyl-CoA dehydrogenase deficiency
      in humans with L-carnitine at an oral dosage of 100 mg/kg BW/day.

PMID- 24893613
TI  - Urotensin II receptor determines prognosis of bladder cancer regulating cell
      motility/invasion.
AB  - BACKGROUND: Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle
      Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile
      and clinical course. NMIBC prognosis is not completely predictable, since the
      relapse rate is higher than 20%, even in the form of MIBC. The aim of this study
      is to evaluate if UTR expression can discriminate between NMIBC and MIBC and
      predict the risk of relapses in NMIBCs. METHODS: We have investigated upon
      urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by
      NMIBC. The biological role of UTR was also investigated in vitro. UTR expression
      was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive
      bTCC samples. RESULTS: UTR discriminated between NMIBC and MIBC and showed a
      significant correlation between low UTR expression and shorter disease free
      survival in NMIBC. The superagonist UPG84 induced growth suppression at nM
      concentrations on 3/4 cell lines. Bladder cancer cell treatment with the
      antagonist urantide or the knock-down of UTR with a specific shRNA significantly
      blocked both the motility and invasion of bladder cancer cells. CONCLUSIONS: The
      evaluation of UTR expression can discriminate between NMIBC at high and low risk
      of relapse. Moreover, our data suggest that UTR is involved in the regulation of
      motility, invasion and proliferation of bladder cancer cells. High UTR expression
      is an independent prognostic factor of good prognosis for NMIBC regulating
      motility and invasion of bladder cancer cells.

PMID- 24893615
TI  - Effects of smoking and preeclampsia on birth weight for gestational age.
AB  - OBJECTIVE: A counterintuitive interaction between smoking during pregnancy and
      preeclampsia on birth weight for gestational age (BWGA) outcomes was recently
      reported. In this report, we examine the relationship between these factors in a
      well-documented study population with exposure data on trimester of maternal
      smoking. METHODS: Preeclamptic (n = 238), gestational hypertensive (n = 219), and
      normotensive women (n = 342) were selected from live-births to nulliparous Iowa
      women. Disease status was verified by medical chart review, and smoking exposure
      was assessed by self-report. Fetal growth was assessed as z-score of BWGA.
      Multiple linear regression was used to test for the association of maternal
      smoking and preeclampsia with BWGA z-score. RESULTS: There was no interaction
      between smoking with preeclampsia or gestational hypertension on fetal growth.
      BWGA z-scores were significantly lower among women with preeclampsia and those
      who smoked any time during pregnancy (beta = -0.33, p = <0.0001 and beta = -0.25,
      p = 0.05) compared to normotensive and non-smoking women, respectively. Infants
      of women with gestational hypertension were comparable in size to infants born to
      normotensive women. CONCLUSIONS: Women who developed preeclampsia and those who
      smoked during pregnancy delivered infants that were significantly smaller than
      infants of women who did not develop preeclampsia and non-smoking women,
      respectively.

PMID- 24893616
TI  - FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q
      and additional cytogenetic abnormalities.
AB  - BACKGROUND: The progression of low-risk del(5q) myelodysplastic syndrome to acute
      myeloid leukemia is increased when associated with mutations of TP53, or with
      additional chromosomal abnormalities. However, to date the prognostic impact and
      molecular consequences of these rearrangements were poorly investigated. Single
      additional alterations to del(5q) by balanced chromosome rearrangements were
      rarely found in myelodysplasia. In particular, balanced alterations involving
      TP63 and FOXP1 genes were never reported in the literature. CASE PRESENTATION:
      Here we report on a 79-year woman with an aggressive form of myelodysplastic
      syndrome with del(5q), no TP53 mutation, and a novel complex rearrangement of
      chromosome 3 in bone marrow cells. Our results revealed that the FOXP1 and TP63
      genes were both relocated along chromosome 3. Strikingly, immunohistochemistry
      analysis showed altered protein levels, disclosing that this rearrangement
      triggered the expression of FOXP1 and TP63 genes. FOXP1 was also found activated
      in other patients with myelodysplasia and acute myeloid leukemia, showing that it
      is an important, recurrent event. CONCLUSIONS: We document an apparent role of
      FOXP1 and TP63, up to now poorly documented, in the progression of MDS in our
      patient who is lacking mutations in the TP53 tumor suppressor gene normally
      associated with poor outcome in myelodysplastic syndrome with 5q-. Finally, our
      results may suggest a possible broader role of FOXP1 in the pathogenesis and
      progression of myelodysplasia and acute myeloid leukemia.

PMID- 24893617
TI  - Nonalcoholic fatty liver disease is associated with significant coronary artery
      disease in type 2 diabetic patients: a computed tomography angiography study 2:.
AB  - BACKGROUND: To investigate whether nonalcoholic fatty liver disease (NAFLD) is
      associated with coronary artery disease (CAD) in type 2 diabetic patients, who
      underwent coronary computed tomography angiography (CTA). METHODS: Between June
      2007 and May 2010, a total of 273 type 2 diabetic patients without known liver
      disease underwent coronary CTA for chest pain were enrolled. Axial, multiplanar,
      and Maximum intensity projection (MIP) images were used for determining the
      cardiovascular disease. Liver fat content was measured from unenhanced CT images
      obtained for calcium scoring. Moderate and severe NAFLD was defined when mean
      liver attenuation value is <=40 Hounsfield Unit (HU). RESULTS: Among 273
      patients, 76% of the patients (n = 207) had CAD; 48% of them had significant CAD
      (>=50 stenosis) by coronary CTA. Patients with CAD were older and male gender was
      predominant. Mean liver attenuation value calculated with CT was 50 +/- 12 HU.
      Mean liver attenuation value was lower in patients with metabolic syndrome
      compared to patients without metabolic syndrome (P < 0.001). Moderate and severe
      NAFLD was observed in 22% of the patients (n = 59) with a mean attenuation value
      of 30 HU. After adjustment of age, gender, obesity, hypertension, smoking status
      and serum low-density lipoprotein (LDL) levels as coronary risk factors, NAFLD
      was associated with significant CAD (P = 0.04). CONCLUSIONS: In conclusion, the
      results of the present study indicate that NAFLD is associated with significant
      CAD in type 2 diabetic patients. Assessment of liver attenuation by CT represents
      noninvasive evaluation for detection of asymptomatic individuals with NAFLD
      during coronary CT angiography.

PMID- 24893618
TI  - Acute thrombotic occlusion of a giant right coronary artery aneurysm.

PMID- 24893620
TI  - Palladium-catalyzed direct arylation of selenophene.
AB  - An efficient and convenient method was developed for the regioselective formation
      of 2-aryl- or 2,5-diarylselenophenes via a palladium-catalyzed direct arylation.
      This protocol is suitable for a wide range of aryl halides containing different
      functional groups. The 2-arylated substrates can undergo an additional
      regioselective direct arylation event furnishing symmetrical or unsymmetrical 2,5
      diaryl selenophenes in good yield. Competition experiments and the role of the
      acid additive are in agreement with a concerted metalation deprotonation (CMD)
      pathway. 

PMID- 24893619
TI  - Anesthetic practice for Caesarean section and factors influencing
      anesthesiologists' choice of anesthesia: a population-based study.
AB  - BACKGROUND: We examined the change in anesthetic practice for Caesarean section
      (CS) during the past decade and determined factors influencing anethesiologists'
      decisions. METHODS: The cases were identified from data retrieved from
      Longitudinal Health Insurance Database released by the Taiwan National Health
      Research Institute in 2008. Trend analysis was performed using logistic
      regression models. The decision tree analysis was performed using the chi-squared
      automatic interaction detector method and multivariable logistic regression
      analysis was performed to identify predictors of general anesthesia. RESULTS: A
      total of 25,606 women undergoing CS were studied. Logistic regression analyses
      revealed an upward trend of spinal anesthesia from 2000 to 2008 [57.8-67.5%,
      adjusted odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.05-1.07, P <
      0.001] and a decreasing trend across time for both general and epidural
      anesthesia (5.5-3.9% and 36.7-28.6%; both OR < 1, both P < 0.001). Patterns of
      change in anesthetic practice across time for emergency and non-emergency CS were
      similar (all P < 0.05). Our data further demonstrated that early or threatened
      labor, a history of preeclampsia, antepartum hemorrhage, emergency CS, and
      previous CS were important predictors that influenced the anesthesiologists'
      choice of general anesthesia versus neuraxial anesthesia for women undergoing CS.
      CONCLUSIONS: Spinal anesthesia was the most common mode of anesthesia for CS
      deliveries in Taiwan during the past decade. Early or threatened labor,
      antepartum hemorrhage, emergency CS, previous CS, and preeclampsia are
      significant determinants of general anesthesia in CS deliveries.

PMID- 24893621
TI  - Moving forward in nursing.

PMID- 24893622
TI  - Photophysical properties and singlet oxygen generation efficiencies of water
      soluble fullerene nanoparticles.
AB  - As various fullerene derivatives have been developed, it is necessary to explore
      their photophysical properties for potential use in photoelectronics and
      medicine. Here, we address the photophysical properties of newly synthesized
      water-soluble fullerene-based nanoparticles and polyhydroxylated fullerene as a
      representative water-soluble fullerene derivative. They show broad emission band
      arising from a wide-range of excitation energies. It is attributed to the optical
      transitions from disorder-induced states, which decay in the nanosecond time
      range. We determine the kinetic properties of the singlet oxygen ((1)O2)
      luminescence generated by the fullerene nanoparticles and polyhydroxylated
      fullerene to consider the potential as photodynamic agents. Triplet state decay
      of the nanoparticles was longer than (1)O2 lifetime in water. Singlet oxygen
      quantum yield of a series of the fullerene nanoparticles is comparably higher
      ranging from 0.15 to 0.2 than that of polyhydroxylated fullerene, which is about
      0.06.

PMID- 24893624
TI  - Etidronate causes minimal changes in the ability of sodium hypochlorite to
      dissolve organic matter.
AB  - AIM: To evaluate the effect of individual and combined use of sodium hypochlorite
      (NaOCl), etidronate (HEDP) and ethylenediaminetetraacetic acid (EDTA) in tissue
      dissolution. METHODOLOGY: Sixty fragments of bovine muscle tissue were prepared
      and their weights determined on a precision scale. The samples were then
      distributed in the following groups (n = 10): G1 - saline solution (control); G2 
      17% EDTA; G3 - 18% HEDP; G4 - 2.5% NaOCl; G5 - mixture of 5% NaOCl + 17% EDTA;
      and G6 - mixture of 5% NaOCl + 18% HEDP. The specimens in each group were
      immersed in the solutions for 5, 10 and 15 min and reweighted at each time
      period. Analysis of variance (anova) and Tukey's multiple-comparison tests
      (alpha<0.05) were applied to identify the intragroup and intergroup differences.
      RESULTS: G1, G2, G3 and G5 did not dissolve the organic matter. G4 and G6
      significantly reduced the weights of specimens at all periods. Amongst the
      groups, the difference in ability to dissolve organic matter was greater and
      significant in the following order G4 = G6 > G5 = G3 = G2 = G1 after 5 min of
      immersion and G4 > G6 > G5 = G3 = G2 = G1 after 10 and 15 min of immersion.
      CONCLUSION: The only solution capable of dissolving organic matter was NaOCl. In
      the mixtures analysed, this ability was arrested by EDTA; however, it was
      minimally affected by the HEDP, proving that this combination, if used during the
      biomechanical preparation, is able to dissolve of organic matter.

PMID- 24893623
TI  - Photoperiodic regulation of hippocampal neurogenesis in adult male white-footed
      mice (Peromyscus leucopus).
AB  - Photoperiodic organisms monitor environmental day length to engage in seasonally
      appropriate adaptions in physiology and behavior. Among these adaptations are
      changes in brain volume and neurogenesis, which have been well described in
      multiple species of birds, yet few studies have described such changes in the
      brains of adult mammals. White-footed mice (Peromyscus leucopus) are an excellent
      species in which to investigate the effects of day length on adult hippocampal
      neurogenesis, as males, in addition to having reduced hippocampal volume in short
      days (SD) with concomitant impairments in hippocampus-mediated behaviors, have
      photoperiod-dependent changes in olfactory bulb neurogenesis. We performed the
      current experiment to assess the effects of photoperiod on hippocampal
      neurogenesis longitudinally, using the thymidine analog bromodeoxyuridine at
      multiple time points across 10 weeks of SD exposure. Compared with counterparts
      held in long day (LD) lengths, across the first 8 weeks of SD exposure
      hippocampal neurogenesis was reduced. However, at 10 weeks in SD lengths
      neurogenic levels in the hippocampus were elevated above those levels in mice
      held in LD lengths. The current findings are consistent with the natural
      photoperiodic cycle of hippocampal function in male white-footed mice, and may
      help to inform research on photoperiodic plasticity in neurogenesis and provide
      insight into how the complex interplay among the environment, genes and adaptive
      responses to changing day lengths affects brain structure, function and behavior
      at multiple levels. 

PMID- 24893625
TI  - Risk assessment for coronary heart disease in patients with haemophilia: a single
      centre study in the United States.
AB  - In haemophilia, coronary heart disease (CHD) occurs at a similar frequency as in
      the general population, but the contributing risk factors in haemophilia are
      incompletely understood. To investigate risk factors and 10-year CHD risk in a
      single centre cohort of patients with haemophilia (PWH) >=20 years old (n = 89).
      We retrospectively applied the modified Framingham National Cholesterol Education
      Program/Adult Treatment Panel (NCEP/ATP) III risk prediction equation. Three risk
      levels were defined: <10% (low), 10-20% (intermediate) and >20% (high). Results
      were compared to the National Health and Nutrition Examination Survey (NHANES).
      Mean age in both cohorts was similar. Compared to NHANES, systolic blood
      pressures were significantly higher in PWH, but current smoking and cholesterol
      were lower. CHD risk differed significantly between PWH and NHANES (P = 0.005)
      with a higher proportion of PWH classified at low risk (77.5% vs. 61.0%). The
      proportion of low risk patients was also significantly higher for severe
      haemophilia patients compared to non-severe haemophilia patients (88.6% vs.
      66.7%, P = 0.02). Among PWH, and compared to PWH who were hepatitis C (HepC)
      negative, HepC positive patients had significantly lower cholesterol, LDL and
      triglycerides. The CHD risk of HepC positive patients differed significantly from
      NHANES (P = 0.03) with a lower proportion of HepC positives being classified as
      high risk (5.7% vs. 17.3%). Favourable CHD risk classification in PWH may be
      influenced by low cholesterol associated with HepC infection. Estimates of CHD
      risk in PWH by composite scoring may not be accurate and will require studies
      correlating risk factors with incident CHD. 

PMID- 24893626
TI  - An instructive viewpoint from the Greek mythology.

PMID- 24893627
TI  - High-dose chemotherapy with autologous stem cell transplantation in relapsed or
      refractory germ cell tumours: outcomes and prognostic variables in a case series
      of 17 patients.
AB  - BACKGROUND: Optimal therapy for men relapsing after initial chemotherapy for germ
      cell tumours (GCT) is poorly defined. Both conventional dose salvage regimens and
      high-dose chemotherapy with autologous stem cell transplantation (HDCT-ASCT) have
      been utilised. AIMS: To examine patients who received HDCT-ASCT for relapsed GCT
      within a single Australian centre. METHODS: Records between 2000 and 2012 were
      analysed for baseline characteristics, treatment-related toxicity and survival.
      Prognosis at the time of HDCT-ASCT was classified according to the International
      Prognostic Factors Study Group (IPFSG). RESULTS: Seventeen patients received HDCT
      ASCT, median age 34 (21-46), with 41% having primary refractory disease and 53%
      with high/very high risk disease by IPFSG. The most common regimen utilised was
      paclitaxel/ifosfamide followed by high-dose carboplatin/etoposide (TI-CE; n =
      12). The median duration of grade 4 (G4) neutropenia was 11 days (range 9-17)
      with febrile neutropenia in 90% resulting in four intensive care unit admissions
      (8%). Median duration of G4 thrombocytopenia was 10 days (range 8-19) requiring a
      median of two pooled platelets bags (range 0-33) per episode. Transplant-related
      mortality occurred in one patient (veno-occlusive disease). Twenty-seven per cent
      of HDCT-ASCT cycles were associated with grade 3 mucositis (median total
      parenteral nutrition days = 5 (0-23)). Two-year progression-free survival (PFS)
      and overall survival (OS) rates were 59% and 71%. Patients who received HDCT-ASCT
      as second or subsequent relapse fared worse than those treated with HDCT-ASCT at
      first relapse (hazard ratio 0.23 (95% confidence interval: 0.04, 1.37; P-value
      0.09). Three-year OS for those who received TI-CE at first relapse was 90%.
      CONCLUSIONS: HDCT-ASCT for relapsed GCT is effective with acceptable toxicity.
      There was encouraging PFS/OS, particularly in a poor-prognosis cohort.

PMID- 24893629
TI  - A RAS renaissance: emerging targeted therapies for KRAS-mutated non-small cell
      lung cancer.
AB  - Of the numerous oncogenes implicated in human cancer, the most common and perhaps
      the most elusive to target pharmacologically is RAS. Since the discovery of RAS
      in the 1960s, numerous studies have elucidated the mechanism of activity,
      regulation, and intracellular trafficking of the RAS gene products, and of its
      regulatory pathways. These pathways yielded druggable targets, such as
      farnesyltransferase, during the 1980s to 1990s. Unfortunately, early clinical
      trials investigating farnesyltransferase inhibitors yielded disappointing
      results, and subsequent interest by pharmaceutical companies in targeting RAS
      waned. However, recent advances including the identification of novel regulatory
      enzymes (e.g., Rce1, Icmt, Pdedelta), siRNA-based synthetic lethality screens,
      and fragment-based small-molecule screens, have resulted in a "Ras renaissance,"
      signified by new Ras and Ras pathway-targeted therapies that have led to new
      clinical trials of patients with Ras-driven cancers. This review gives an
      overview of KRas signaling pathways with an emphasis on novel targets and
      targeted therapies, using non-small cell lung cancer as a case example.

PMID- 24893628
TI  - Toll-like receptor agonist imiquimod facilitates antigen-specific CD8+ T-cell
      accumulation in the genital tract leading to tumor control through IFNgamma.
AB  - PURPOSE: Imiquimod is a Toll-like receptor 7 agonist used topically to treat
      external genital warts and basal cell carcinoma. We examined the combination of
      topical imiquimod with intramuscular administration of CRT/E7, a therapeutic
      human papillomavirus (HPV) vaccine comprised of a naked DNA vector expressing
      calreticulin fused to HPV16 E7. EXPERIMENTAL DESIGN: Using an orthotopic HPV16
      E6/E7(+) syngeneic tumor, TC-1, as a model of high-grade cervical/vaginal/vulvar
      intraepithelial neoplasia, we assessed if combining CRT/E7 vaccination with
      cervicovaginal deposition of imiquimod could result in synergistic activities
      promoting immune-mediated tumor clearance. RESULTS: Imiquimod induced
      cervicovaginal accumulation of activated E7-specific CD8(+) T cells elicited by
      CRT/E7 vaccination. Recruitment was not dependent upon the specificity of the
      activated CD8(+) T cells, but was significantly reduced in mice lacking the
      IFNgamma receptor. Intravaginal imiquimod deposition induced upregulation of
      CXCL9 and CXCL10 mRNA expression in the genital tract, which are produced in
      response to IFNgamma receptor signaling and attract cells expressing their
      ligand, CXCR3. The T cells attracted by imiquimod to the cervicovaginal tract
      expressed CXCR3 as well as CD49a, an integrin involved in homing and retention of
      CD8(+) T cells at mucosal sites. Our results indicate that intramuscular CRT/E7
      vaccination in conjunction with intravaginal imiquimod deposition recruits
      antigen-specific CXCR3(+) CD8(+) T cells to the genital tract. CONCLUSIONS:
      Several therapeutic HPV vaccination clinical trials using a spectrum of DNA
      vaccines, including vaccination in concert with cervical imiquimod, are ongoing.
      Our study identifies a mechanism by which these strategies could provide
      therapeutic benefit. Our findings support accumulating evidence that manipulation
      of the tumor microenvironment can enhance the therapeutic efficacy of strategies
      that induce tumor-specific T cells.

PMID- 24893630
TI  - An unconventional KITENIN/ErbB4-mediated downstream signal of EGF upregulates c
      Jun and the invasiveness of colorectal cancer cells.
AB  - PURPOSE: EGF-stimulated signaling via EGF receptor (EGFR) is important in
      colorectal tumorigenesis and drug targeting. However, anti-EGFR therapy is not
      effective in a subset of patients with colorectal cancer, suggesting that
      unidentified EGF-stimulated pathways might play roles in colorectal cancer.
      Previously, we identified KAI1 C-terminal interacting tetraspanin (KITENIN) as a
      metastasis-enhancing gene and found it to be highly expressed in sporadic
      colorectal cancer tissues. We recently found that EGF further increases KITENIN
      induced elevated AP-1 activity. Here we attempted to clarify this novel EGF
      stimulated molecular pathway and its roles in colorectal cancer. EXPERIMENTAL
      DESIGN: We analyzed how EGF modulates the downstream signaling pathway of
      oncogenic KITENIN in colorectal cancer cells. Biological alterations following
      EGF treatment were identified in KITENIN-overexpressed colorectal cancer cells
      with or without alteration of EGFR activity. RESULTS: We identified the
      KITENIN/ErbB4-Dvl2-c-Jun axis as a novel downstream signal of EGF that is
      switched on under elevated KITENIN conditions in an EGFR-independent manner. This
      unconventional EGF signal upregulates c-Jun and enhances invasion and anchorage
      independent growth of colorectal cancer cells. In addition, tumor tissues from
      metastatic patients with colorectal cancer who showed initial poor responses to
      cetuximab/chemotherapy expressed higher levels of KITENIN than did responders to
      therapy. CONCLUSIONS: Our results highlight the role of an EGFR-independent EGF
      signal in mediating the invasiveness and tumorigenesis of colorectal cancer
      cells. This unconventional pathway might be related to the limited clinical
      efficacy of anti-EGFR agents in a subset of patients with colorectal cancer.

PMID- 24893632
TI  - The Split initiative, chapter 2.

PMID- 24893631
TI  - Neuroblastoma killing properties of Vdelta2 and Vdelta2-negative gammadeltaT
      cells following expansion by artificial antigen-presenting cells.
AB  - PURPOSE: The majority of circulating human gammadeltaT lymphocytes are of the
      Vgamma9Vdelta2 lineage, and have T-cell receptor (TCR) specificity for nonpeptide
      phosphoantigens. Previous attempts to stimulate and expand these cells have
      therefore focused on stimulation using ligands of the Vgamma9Vdelta2 receptor,
      whereas relatively little is known about variant blood gammadeltaT subsets and
      their potential role in cancer immunotherapy. EXPERIMENTAL DESIGN: To expand the
      full repertoire of gammadeltaT without bias toward specific TCRs, we made use of
      artificial antigen-presenting cells loaded with an anti gammadeltaTCR antibody
      that promoted unbiased expansion of the gammadeltaT repertoire. Expanded cells
      from adult blood donors were sorted into 3 populations expressing respectively
      Vdelta2 TCR chains (Vdelta2(+)), Vdelta1 chains (Vdelta1(+)), and TCR of other
      delta chain subtypes (Vdelta1(neg)Vdelta2(neg)). RESULTS: Both freshly isolated
      and expanded cells showed heterogeneity of differentiation markers, with a less
      differentiated phenotype in the Vdelta1 and Vdelta1(neg)Vdelta2(neg) populations.
      Expanded cells were largely of an effector memory phenotype, although there were
      higher numbers of less differentiated cells in the Vdelta1(+) and
      Vdelta1(neg)Vdelta2(neg) populations. Using neuroblastoma tumor cells and the
      anti-GD2 therapeutic mAb ch14.18 as a model system, all three populations showed
      clinically relevant cytotoxicity. Although killing by expanded Vdelta2 cells was
      predominantly antibody dependent and proportionate to upregulated CD16, Vdelta1
      cells killed by antibody-independent mechanisms. CONCLUSIONS: In conclusion, we
      have demonstrated that polyclonal-expanded populations of gammadeltaT cells are
      capable of both antibody-dependent and -independent effector functions in
      neuroblastoma.

PMID- 24893633
TI  - The sensitivity of male rat reproductive organs to monosodium glutamate.
AB  - OBJECTIVE: This study aimed to investigate the sensitivity of the testis,
      epididymis, seminal vesicle, and sperm acrosome reaction (AR) to monosodium L-
      glutamate (MSG) in rats. MATERIALS AND METHODS: Rats were divided into four
      groups and fed with non-acidic MSG at 0.25, 3 or 6 g/kg body weight for 30 days
      or without MSG. The morphological changes in the reproductive organs were
      studied. The plasma testosterone level, epididymal sperm concentration, and sperm
      AR status were assayed. RESULTS: Compared to the control, no significant changes
      were discerned in the morphology and weight of the testes, or the histological
      structures of epididymis, vas deferens and seminal vesicle. In contrast,
      significant decreases were detected in the weight of the epididymis, testosterone
      levels, and sperm concentration of rats treated with 6 g/kg body weight of MSG.
      The weight loss was evident in the seminal vesicle in MSG-administered rats.
      Moreover, rats treated with MSG 3 and 6 g/kg exhibited partial testicular damage,
      characterized by sloughing of spermatogenic cells into the seminiferous tubular
      lumen, and their plasma testosterone levels were significantly decreased. In the
      6 g/kg MSG group, the sperm concentration was significantly decreased compared
      with the control or two lower dose MSG groups. In AR assays, there was no
      statistically significant difference between MSG-rats and normal rats.
      CONCLUSION: Testicular morphological changes, testosterone level, and sperm
      concentration were sensitive to high doses of MSG while the rate of AR was not
      affected. Therefore, the consumption of high dose MSG must be avoided because it
      may cause partial infertility in male.

PMID- 24893634
TI  - Most common HCV genotypes in patients from north-eastern Croatia.
AB  - OBJECTIVE: The aims of this study were to determine the HCV-RNA viral load,
      genotype distribution, risk factors and symptoms of HCVRNA positive viral load in
      HCV antibody-positive patients from north-eastern Croatia. MATERIALS AND METHODS:
      From January 2009 to December 2011, 203 HCV antibody- positive patients (130 men
      and 73 women; median age 44.5 years) were analyzed for HCV-RNA by the COBAS
      TaqMan HCV test and genotyped by the Linear Array HCV Genotyping test (both from
      Roche). All patients completed a structured questionnaire about risk factors and
      symptoms. RESULTS: The HCV-RNA percentage was 61.1% and was similar for men and
      women. The HCV-RNA viral load increased with age: while 55% of 20-50 year old
      patients were HCV-RNA positive, 73% of patients >50 years were positive
      (p=0.021). Genotype 1 was the most prevalent genotype (79.8%), followed by 3
      (12.9%), 4 (6.5%), and 2 (0.8%); genotypes 5 and 6 were not determined. Patients
      with genotype 1 (median, 50 years) were older than patients with 3 (median, 33.5
      years) or 4 (median, 38 years). The blood transfusions performed in Croatian
      hospitals before 1993 was significantly associated with HCV-RNA positive viral
      load (p<0.05). CONCLUSION: These data indicated an elevated prevalence of
      genotype 1 in elderly HCV-RNA positive patients and it may continue to rise.
      Using RNA-based detection in HCV positive-antibody patients would allow early
      detection of HCV in the acute stage of HCV disease and the increased risk of HCV
      genotyperelated treatment failure.

PMID- 24893635
TI  - Immune responses following McKenzie lumbar spine exercise in individuals with
      acute low back pain: a preliminary study.
AB  - OBJECTIVE: This study explores the immune responses following 4 weeks of McKenzie
      lumbar spine exercise in individuals with acute low back pain (ALBP). PATIENTS
      AND METHODS: Fifteen patients with ALBP and 15 healthy individuals volunteered in
      this study. Ten ml of peripheral blood were obtained from each patient before and
      after exercise sessions, and from healthy individuals at the beginning of the
      study. Flow cytometric analysis was used to evaluate the frequencies of CD4+ T
      lymphocyte sub-populations and the intracellular cytokine expression within this
      cell population. Pain perceptions were obtained at baseline and following each
      week of exercise sessions. RESULTS: In comparison with healthy subjects there was
      an elevated frequency of memory (CD4+CD45RO+) T cells, helper inducer (CD4+CD29+)
      T cells, CD3+CD16+CD56+ T cells and a lower frequency of naive/suppressor
      (CD4+CD45RA+) T cells at base line in back pain patients (p<0.05). After 4 weeks
      of McKenzie exercise sessions, pain intensity significantly decreased (p<0.05);
      however, there was no significant difference in the frequency of memory
      (CD4+CD45RO+) T cells, helper inducer (CD4+CD29+) T cells, CD3+CD16+CD56+ T cells
      and naive/ suppressor (CD4+CD45RA+) T cells at base line relative to these cell
      populations after exercise sessions. The percentage of Pan (CD3+) T cells
      expressing IL-8 and TNF-alpha and the CD3+ T cells expressing the anti
      inflammatory cytokine IL-4 increased significantly (p<0.05) following exercise
      sessions in comparison with baseline and healthy references. The reduction in
      pain scores did not correlate with elevated anti-inflammatory cytokines.
      CONCLUSION: McKenzie exercise sessions induced an immune activation state and
      simultaneously up regulated anti-inflammatory IL-4 cytokines that boost pain
      relief.

PMID- 24893636
TI  - International textbook of family medicine: the application of EURACT teaching
      agenda.
AB  - The paper describes experiences in the development of an international textbook
      of family medicine. The process of its development has started in Slovenia, where
      the Slovenian authors have written a textbook, adhering strictly to the European
      definition of family medicine and its core competencies. The format and the
      approach were also adopted by Croatian authors, who have used most of the
      material from the Slovenian book, but have modified some of the chapters
      according to the situation in the country and have added some of their own. This
      activity has created an opportunity for a truly international collaboration in
      the area of education of family medicine, with a creation of an international
      consortium, which would be responsible for the core content of the book and local
      adaptations of the book according to the specificities and needs of different
      countries. CONCLUSION: This innovative approach in the development of teaching
      material may be interesting for a variety of smaller countries in Europe and
      worldwide.

PMID- 24893637
TI  - Satisfaction with the program of school bullying prevention and mental health
      promotion - cross sectional study among primary school pupils in Mostar.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of experience in
      school bullying and family violence, satisfaction with the preventive-promotional
      program, knowledge about methods for opposing violence and attitudes toward the
      role of the family physician in bullying prevention. MATERIALS AND METHODS: The
      project was conducted by family physicians, nurses and sixth year medical
      students. The target group were 5th to 8th grade pupils of two primary schools
      randomly selected by computer. Basic information about the presence and types of
      bullying, the long-term consequences of violence and methods to oppose violent
      behavior was given as an interactive lecture to large groups of pupils. After the
      lecture, pupils received questionnaires about their experience of school
      violence, satisfaction with the program and their opinion about the role of the
      family physician in bullying prevention. RESULTS: The results of the short term
      outcome evaluation of the program show that younger pupils evaluate the program
      better than older ones. Furthermore, we found that the frequency of experienced
      violence is not connected with satisfaction with the program. CONCLUSION: Most
      students have never experienced violence in schools and families, 5th and 6th
      grade students showed greater satisfaction with training, better knowledge of
      help in case of violence and a more positive attitude towards medical help. We
      found no significant differences in pupil's satisfaction with the program,
      knowledge about methods of opposing violence and attitudes towards the role of
      the family physician in bullying prevention, in relation to the frequency of
      experience of family violence and school violence.

PMID- 24893638
TI  - Final year medical students' understanding of family medicine.
AB  - OBJECTIVE: The European Academy of Teachers in General Practice / Family Medicine
      (EURACT) has developed an educational agenda, the key document for teaching
      family medicine in Europe. The aim of our study was to find out how final year
      medical students at the beginning of their family medicine clerkship understand
      the discipline of family medicine. METHODS: The attitudes toward family medicine
      were paraphrased and developed into a 164-item questionnaire, which was
      administered to 335 final-year medical students at the beginning of their
      clerkship. Using combinatorial optimization with genetic algorithms we selected
      30 items which yielded the highest Cronbach alpha reliability coefficient.
      Finally, we performed a factor analysis to find which dimensions of family
      medicine were recognised by the students and compared them with the domains
      defined in the EURACT definition. RESULTS: The 30-item questionnaire had a
      Cronbach alpha reliability coefficient of 0.919. The differences between male and
      female students were not very significant (p=0.061). With the factor analysis we
      recognised seven factors, belonging to three out of six domains of the EURACT
      educational agenda: primary care management, personcenteredness and comprehensive
      approach. CONCLUSION: Final-year medical students at the beginning of their
      family medicine clerkship understand some of the dimensions of family medicine
      rather well, but they are not aware of some important competences of family
      doctors. There is a necessity to teach students about specific problem solving
      skills and the importance of balance between the health needs of an individual
      patient and the community.

PMID- 24893639
TI  - Teaching science throughout the six-year medical curriculum: two-year experience
      from the University of Split School of Medicine, Split, Croatia.
AB  - OBJECTIVE: The aim of this article is to present the introduction of a mandatory,
      vertically integrated course in research methodology into medical curriculum. At
      the School of Medicine in Split (Croatia) we organized this course in 2010, with
      the total of 270 hours in the 6-year curriculum. In the first year (50 hours)
      students learned basic principles of scientific method, structure of scientific
      article, basic statistical concepts, data analysis, interpretation and
      presentation. In the second year (25 hours) students applied the knowledge from
      the first year in real examples of research data to answer a research hypothesis
      and present the results and conclusions. Students were guided through the process
      of making a hypothesis, analyzing data, interpreting them, constructing tables
      and figures, and writing a short research report. At the end of the course they
      formally presented the results to other students and course teachers, using
      PowerPoint slides. The third year (25 hours) was devoted to mastering concepts
      and basic skills of evidencebased medicine (EBM). The course in the fourth year
      (25 hours) was integrated with the clinical courses (internal medicine,
      neurology, and psychiatry) and structured as a "journal club". In the fifth year
      (25 hours), the teaching was devoted to developing a research plan for the
      graduation thesis that the students had to conduct during the sixth year. The
      sixth year (120 hours) was devoted to the execution of research planned in the
      fifth year, including data collection, data analysis, interpretation, and thesis
      writing and defense. CONCLUSION: The new course succeeded in increasing students'
      knowledge and skills for critical thinking and EBM, and prepared them for life
      long learning in medicine.

PMID- 24893640
TI  - Importance of international networking in academic family medicine.
AB  - European family medicine/general practice (FM/GP) has travelled the long and
      successful journey of profiling the discipline and has produced valuable position
      papers on education and research. Nowadays, academic medicine is one of the
      pillars in the future development of FM/GP in Europe. A common European
      curriculum on undergraduate and postgraduate family medicine is needed. Also, a
      sound international platform of teaching institutions and/or teachers of family
      medicine would foster the further development of family medicine as an academic
      discipline. This would stimulate students and teachers to engage in international
      exchange to gain new knowledge and experiences, present their work and ideas
      abroad and prepare the conditions for further exchange of students and teachers.
      CONCLUSION: Established departments of FM/GP, led by a teacher who is a family
      physician/general practitioner, at each Medical School in Europe should provide
      students with knowledge and skills related to the core attributes of FM/GP.
      International exchanges of teachers and students should foster the development of
      a common curriculum on FM in Europe and foster improvement in the quality of FM
      education.

PMID- 24893641
TI  - Academic cooperation in family medicine: a viewpoint from Split.
AB  - The problems, current status, and opportunities of national and international
      collaboration between the academic family medicine institutions in Southern
      Europe, particularly in the region of ex Yugoslavia, as perceived from the
      standpoint of the Department of Family Medicine in Split University School of
      Medicine, Split, Croatia, are presented in this brief review. A historical survey
      of this department's educational, professional, and scientific development from
      its establishment in 1997 is given to place the regional issues in context.
      Family physicians are strong in number here - around 53 family practitioners per
      100,000 inhabitants in Croatia, similar to surrounding countries, but weak in
      academic representation, with only 18 active faculty members. This compares to
      general internal medicine with 28 practitioners per 100,000 inhabitants and 106
      active faculty members. The reasons for such a disproportion are analyzed, and
      the importance of collaboration is stressed. CONCLUSION: Although there have been
      several cooperative efforts, these activities can and should be intensified.
      While there is much work to be done, there are many opportunities for
      improvement.

PMID- 24893642
TI  - Academic model of trauma healing in post-war societies.
AB  - OBJECTIVE: The aim of this paper is to examine the implications for healing in a
      contemporary Balkan post-war context, and to provide a bridge-building model of
      trauma transformation, reconciliation and recovery through academic
      reconstruction and cross-border dialogue. Post-war societies are marked by the
      effects of massive, large group traumatization, and if not properly dealt with,
      long-term rehabilitation and social recovery cannot be expected. Unprocessed
      cumulative trauma that has become deeply embedded in the collective memory of the
      Balkan peoples over centuries, "chosen trauma", its trans-generational
      transmission and periodical reactivations across the Balkan have often been
      addressed in recent literature, in ethno-psychology, psychoanalysis, psychiatry,
      sociology and anthropology. In order to deepen our understanding of the roots of
      collective (social) trauma and the specific traumatic experiences of different
      groups, and to offer different perspectives and information on how trauma can be
      dealt with, the "Trauma Trust Memory" multinational interdisciplinary research
      network is being established, and a groundbreaking workshop was held in May 2013
      in Tuzla, Bosnia-Herzegovina. CONCLUSION: The Tuzla Workshop showed that the
      active participation of affected groups in adequate coping with the past is
      required for post-conflict reconstruction, trauma healing and peacebuilding in
      the long run.

PMID- 24893643
TI  - Research projects in family medicine funded by the European Union.
AB  - OBJECTIVE: This study aimed at synthesizing funding opportunities in the field of
      family medicine by determining the number of family medicine projects, as well as
      number of project leaderships and/ or participations by each country. This was
      done in order to encourage inclusion of physicians in countries with
      underdeveloped research networks in successful research networks or to encourage
      them to form new ones. METHODS: We searched the Community Research and
      Development Information Service project database in February 2013. Study covered
      the period from years 1992 - 2012, selecting the projects within the field of
      general/family medicine. The search was conducted in February 2013. RESULTS:
      First search conducted in the CORDIS database came up with a total of 466
      projects. After excluding 241 projects with insufficient data, we analysed 225
      remaining projects; out of those, 22 (9.8%) were in the field of family medicine
      and 203 (90.2%) were from other fields of medicine. Sorted by the number of
      projects per country, Dutch institutions had the highest involvement in family
      medicine projects and were partners or coordinators in 18 out of 22 selected
      projects (81.8%), followed by British institutions with 15 (68.8%), and Spanish
      with 10 projects (45.5%). Croatia was a partner in a single FP7 Health project.
      CONCLUSION: Research projects in family medicine funded by the European Union
      show significant differences between countries. Constant and high-quality
      international cooperation in family medicine is the prerequisite for improvement
      and development of scientific research and the profession.

PMID- 24893644
TI  - "Fundamental communication skills in medical practice" as minor elective subject.
AB  - OBJECTIVE: Poor and inadequate communication affects the therapeutic relationship
      between doctors and patients. Guided by this idea, we organized a minor elective
      course entitled "communication skills". We wanted to bring closer to the students
      the holistic approach of the family physician to the patient, the importance of
      the family, its impact on the patient and vice versa, and the significance of the
      local community and its influence on an individual's health. The aim of this
      article is to explain how we organized this elective course. METHODS: The course
      was organized in the form of 12 hours of theory (3 lectures and 9 seminars) and
      24 hours of practical training. There were 26 students from all years. Through
      theory, and even more through the practical part the students met with different
      types of patients. RESULTS: At the end of the course, students in lower years
      were evaluated by means of an interview, and graduate students through a
      practical test - a conversation with a patient. The initial results, including
      the students' grading of this course, were highly encouraging. Both teachers and
      students were highly satisfied on completion of the course. CONCLUSION: Content
      on communication training is rare in teaching. Practicing communication skills
      will empower the doctor - patient therapeutic relationship.

PMID- 24893645
TI  - Delayed diagnosis of cleidocranial dysplasia in an adult: a case report.
AB  - OBJECTIVE: To describe a rare case of cleidocranial dysplasia, an autosomal
      dominant inherited disease involving the skeleton and teeth, with delayed
      diagnosis. CASE REPORT: We report a 24-year-old man with cleidocranial dysplasia
      admitted with hearing loss, rhinolalia, dyspnea and fatigue. Partial absence of
      clavicles, a bell-shaped ribcage, an open frontal fontanel, unerupted permanent
      teeth and broad sutures were identified at radiographic examination. CONCLUSION:
      Cleidocranial dysplasia is very rare, and is commonly missed or diagnosed late.
      Radiographic findings are essential for diagnosis. An open frontal fontanel is a
      particularly important finding for neurosurgeons in diagnosis. We describe this
      rare case and discuss the clinical features of CCD.

PMID- 24893646
TI  - Vein of trolard sign on noncontrast computed tomography in Behcet's disease.

PMID- 24893647
TI  - SiRNA screening to identify ubiquitin and ubiquitin-like system regulators of
      biological pathways in cultured mammalian cells.
AB  - Post-translational modification of proteins with ubiquitin and ubiquitin-like
      molecules (UBLs) is emerging as a dynamic cellular signaling network that
      regulates diverse biological pathways including the hypoxia response,
      proteostasis, the DNA damage response and transcription. To better understand how
      UBLs regulate pathways relevant to human disease, we have compiled a human siRNA
      "ubiquitome" library consisting of 1,186 siRNA duplex pools targeting all known
      and predicted components of UBL system pathways. This library can be screened
      against a range of cell lines expressing reporters of diverse biological pathways
      to determine which UBL components act as positive or negative regulators of the
      pathway in question. Here, we describe a protocol utilizing this library to
      identify ubiquitome-regulators of the HIF1A-mediated cellular response to hypoxia
      using a transcription-based luciferase reporter. An initial assay development
      stage is performed to establish suitable screening parameters of the cell line
      before performing the screen in three stages: primary, secondary and
      tertiary/deconvolution screening. The use of targeted over whole genome siRNA
      libraries is becoming increasingly popular as it offers the advantage of
      reporting only on members of the pathway with which the investigators are most
      interested. Despite inherent limitations of siRNA screening, in particular false
      positives caused by siRNA off-target effects, the identification of genuine novel
      regulators of the pathways in question outweigh these shortcomings, which can be
      overcome by performing a series of carefully undertaken control experiments.

PMID- 24893648
TI  - Generation of shear adhesion map using SynVivo synthetic microvascular networks.
AB  - Cell/particle adhesion assays are critical to understanding the biochemical
      interactions involved in disease pathophysiology and have important applications
      in the quest for the development of novel therapeutics. Assays using static
      conditions fail to capture the dependence of adhesion on shear, limiting their
      correlation with in vivo environment. Parallel plate flow chambers that quantify
      adhesion under physiological fluid flow need multiple experiments for the
      generation of a shear adhesion map. In addition, they do not represent the in
      vivo scale and morphology and require large volumes (~ml) of reagents for
      experiments. In this study, we demonstrate the generation of shear adhesion map
      from a single experiment using a microvascular network based microfluidic device,
      SynVivo-SMN. This device recreates the complex in vivo vasculature including
      geometric scale, morphological elements, flow features and cellular interactions
      in an in vitro format, thereby providing a biologically realistic environment for
      basic and applied research in cellular behavior, drug delivery, and drug
      discovery. The assay was demonstrated by studying the interaction of the 2 um
      biotin-coated particles with avidin-coated surfaces of the microchip. The entire
      range of shear observed in the microvasculature is obtained in a single assay
      enabling adhesion vs. shear map for the particles under physiological conditions.

PMID- 24893649
TI  - Manufacturing of robust natural fiber preforms utilizing bacterial cellulose as
      binder.
AB  - A novel method of manufacturing rigid and robust natural fiber preforms is
      presented here. This method is based on a papermaking process, whereby loose and
      short sisal fibers are dispersed into a water suspension containing bacterial
      cellulose. The fiber and nanocellulose suspension is then filtered (using vacuum
      or gravity) and the wet filter cake pressed to squeeze out any excess water,
      followed by a drying step. This will result in the hornification of the bacterial
      cellulose network, holding the loose natural fibers together. Our method is
      specially suited for the manufacturing of rigid and robust preforms of
      hydrophilic fibers. The porous and hydrophilic nature of such fibers results in
      significant water uptake, drawing in the bacterial cellulose dispersed in the
      suspension. The bacterial cellulose will then be filtered against the surface of
      these fibers, forming a bacterial cellulose coating. When the loose fiber
      bacterial cellulose suspension is filtered and dried, the adjacent bacterial
      cellulose forms a network and hornified to hold the otherwise loose fibers
      together. The introduction of bacterial cellulose into the preform resulted in a
      significant increase of the mechanical properties of the fiber preforms. This can
      be attributed to the high stiffness and strength of the bacterial cellulose
      network. With this preform, renewable high performance hierarchical composites
      can also be manufactured by using conventional composite production methods, such
      as resin film infusion (RFI) or resin transfer molding (RTM). Here, we also
      describe the manufacturing of renewable hierarchical composites using double bag
      vacuum assisted resin infusion.

PMID- 24893651
TI  - A novel, nested, multiplex, real-time PCR for detection of bacteria and fungi in
      blood.
AB  - BACKGROUND: The study describes the application of the PCR method for the
      simultaneous detection of DNA of Gram-negative bacteria, Gram-positive bacteria,
      yeast fungi and filamentous fungi in blood and, thus, a whole range of microbial
      etiological agents that may cause sepsis. Material for the study was sterile
      blood inoculated with four species of microorganisms (Escherichia coli,
      Staphylococcus aureus, Candida albicans and Aspergillus fumigatus) and blood
      collected from patients with clinical symptoms of sepsis. The developed method is
      based on nested-multiplex real-time PCR . RESULTS: Analysis of the obtained data
      shows that sensitivity of nested-multiplex real-time PCR remained at the level of
      10(1) CFU/ml for each of the four studied species of microorganisms and the
      percentage of positive results of the examined blood samples from the patients
      was 70% and 19% for the microbiological culture method. The designed primers
      correctly typed the studied species as belonging to the groups of Gram-positive
      bacteria, Gram-negative bacteria, yeast fungi, or filamentous fungi. CONCLUSIONS:
      Results obtained by us indicated that the designed PCR methods: (1) allow to
      detect bacteria in whole blood samples, (2) are much more sensitive than culture
      method, (3) allow differentiation of the main groups of microorganisms within a
      few hours.

PMID- 24893652
TI  - Tailoring magnetic skyrmions in ultra-thin transition metal films.
AB  - Skyrmions in magnetic materials offer attractive perspectives for future
      spintronic applications since they are topologically stabilized spin structures
      on the nanometre scale, which can be manipulated with electric current densities
      that are by orders of magnitude lower than those required for moving domain
      walls. So far, they were restricted to bulk magnets with a particular chiral
      crystal symmetry greatly limiting the number of available systems and the
      adjustability of their properties. Recently, it has been experimentally
      discovered that magnetic skyrmion phases can also occur in ultra-thin transition
      metal films at surfaces. Here we present an understanding of skyrmions in such
      systems based on first-principles electronic structure theory. We demonstrate
      that the properties of magnetic skyrmions at transition metal interfaces such as
      their diameter and their stability can be tuned by the structure and composition
      of the interface and that a description beyond a micromagnetic model is required
      in such systems. 

PMID- 24893650
TI  - Refinement-cut: user-guided segmentation algorithm for translational science.
AB  - In this contribution, a semi-automatic segmentation algorithm for (medical) image
      analysis is presented. More precise, the approach belongs to the category of
      interactive contouring algorithms, which provide real-time feedback of the
      segmentation result. However, even with interactive real-time contouring
      approaches there are always cases where the user cannot find a satisfying
      segmentation, e.g. due to homogeneous appearances between the object and the
      background, or noise inside the object. For these difficult cases the algorithm
      still needs additional user support. However, this additional user support should
      be intuitive and rapid integrated into the segmentation process, without breaking
      the interactive real-time segmentation feedback. I propose a solution where the
      user can support the algorithm by an easy and fast placement of one or more seed
      points to guide the algorithm to a satisfying segmentation result also in
      difficult cases. These additional seed(s) restrict(s) the calculation of the
      segmentation for the algorithm, but at the same time, still enable to continue
      with the interactive real-time feedback segmentation. For a practical and genuine
      application in translational science, the approach has been tested on medical
      data from the clinical routine in 2D and 3D. 

PMID- 24893653
TI  - Do we need radiological guidance for intra-articular hip injections?
AB  - There is still a debate as to whether radiological guidance is needed for intra
      articular hip injections. The aim of this study was to evaluate correct needle
      positioning for the hip joint performed with a non-radiological method and
      confirmed on arthrogram under image intensifier. Patients listed for diagnostic
      and therapeutic hip joint injections were included in our study. Eighty seven
      patients (100 hips) underwent injections with the non-radiological method using
      anatomical landmarks. Fluoroscopy and arthrogram were then used to confirm the
      needle position. The primary outcome measure was the success rate of correct
      positioning of the needle in hip joint by the non-radiological method, as
      confirmed on arthrogram under image intensifier. The secondary outcome measures
      were relationship between the grade of the surgeon and patient BMI to success
      rate of hip injections by the non-radiological method. Overall success rate with
      the non-radiological method was 67%. Consultants were 77.1% successful and
      registrars 57.7% (P = 0.039). The average body mass index (BMI) in the successful
      group was 28.45 (SD = 5.21) and 32.03 (SD = 4.84) in the unsuccessful group
      (p=0.001). Success was further improved to 88% when performed by a consultant in
      low BMI (< 30) patients. This prospective study shows that hip injections can be
      performed with reasonable success without radiological guidance. Experienced
      surgeons may be able to perform this procedure in outpatient clinics in normal
      BMI patients; thereby reducing costs and the need for bed space. 

PMID- 24893654
TI  - A qualitative assessment of health seeking practices among and provision
      practices for men who have sex with men in Malawi.
AB  - BACKGROUND: In the context of a generalized epidemic and criminalization of
      homosexuality, men who have sex with men (MSM) in Malawi have a disproportionate
      burden of HIV compared to other adults. Past research has documented low uptake
      of HIV prevention and health services among MSM, self-reported fear of seeking
      health services, and concerns of disclosure of sexual orientation and
      discrimination in health settings. Qualitative research was conducted among MSM
      and health service providers in Blantyre, Malawi to understand underlying factors
      related to disclosure and health seeking behaviors and inform the development of
      a community-based comprehensive HIV prevention intervention. METHODS: Using peer
      recruitment, eight MSM participants representing a range of ages, orientations,
      and social and behavioral characteristics were enrolled for in-depth interviews.
      Five service providers were recruited from the district hospital, local health
      and STI clinics, and a HIV prevention service organization. We use the Health
      Belief Model as a framework to interpret the influential factors on 1) health
      seeking and uptake among MSM, and 2) influences on provision of services by
      healthcare providers for MSM. RESULTS: Results highlight disclosure fears among
      MSM and, among providers, a lack of awareness and self-efficacy to provide care
      in the face of limited information and political support. Service providers
      reported concerns of adverse repercussions related to the provision of services
      to men in same sex sexual relationships. Some MSM demonstrated awareness of HIV
      risk but believed that within the wider MSM community, there was a general lack
      of HIV information for MSM, low awareness of appropriate prevention, and low
      perception of risks related to HIV infection. CONCLUSIONS: Qualitative research
      highlights the need for appropriate information on both HIV risks and acceptable,
      effective HIV prevention options for MSM. Information and educational
      opportunities should be available to the wider MSM community and the health
      sector. Health sector interventions may serve to increase cultural and clinical
      competency to address health problems experienced by MSM. To ensure availability
      and use of services in light of the criminalization and stigmatization of same
      sex practices, there is need to increase the safety of uptake and provision of
      these services for MSM.

PMID- 24893656
TI  - Copper-catalysed oxidative Csp(3)-H methylenation to terminal olefins using DMF.
AB  - A copper-catalysed direct oxidative Csp(3)-H methylenation to terminal olefins
      using DMF as one carbon source was developed. In this reaction, various
      functional groups were well tolerated, thus providing a simple way to construct
      arylvinylketones and arylvinylpyridines. The preliminary mechanistic
      investigations revealed that CH2 was from DMF (N-CH3). 

PMID- 24893655
TI  - The influence of experimental infection of gilts with swine H1N2 influenza A
      virus during the second month of gestation on the course of pregnancy,
      reproduction parameters and clinical status.
AB  - BACKGROUND: The course of swine influenza in pigs is reported to be similar to
      human influenza. Occasionally abortions and other reproduction disorders have
      been associated with influenza A virus (IAV) infection in pigs. Abortions may be
      a consequence of high fever, pro-inflammatory cytokines or transplacental
      transmission of the virus.The role of IAV in the complications observed during
      pregnancy has been scanty and the true importance of this agent as a cause of
      reproductive problems in swine is not known. The aim was to determine the
      possible involvement of swine H1N2 IAV strain on reproductive disorders in
      pregnant gilts under experimental conditions. RESULTS: The gestation length was
      from 113 to 116 days, no abortion or any other reproduction disorders were noted.
      A PCR assay confirms the presence of IAV in the nasal swabs taken from inoculated
      gilts between 1 and 5 dpi. In the nasal swabs from control gilts and newborn
      piglets, no IAV genetic material was found. No viral RNA was detected in samples
      of blood taken from gilts and piglets, placentas, lungs and tracheas taken from
      piglets euthanized after delivery. The significant decrease in the number and
      percentage of lymphocytes without leukopenia was observed at 4 dpi in inoculated
      gilts. The percentage of granulocytes increased significantly at 4 dpi in
      inoculated pigs. The concentration of IL-6, IL-10 and TNF-alpha were higher in
      inoculated gilts, while IL-4 and IFN-gamma were not detected in the serum of any
      of animals. The serum concentrations of C-reactive protein remained stable during
      study, while haptoglobin concentrations increased significantly after
      inoculation. CONCLUSIONS: The results of the study indicate that infection of
      pregnant gilts with swine H1N2 IAV in the second month of pregnancy does not
      cause abortion and other reproduction disorders. No evidence for transplacental
      transmission of swine H1N2 IAV was found. However, due to subclinical course of
      influenza in the present experiment caution should be taken in extrapolating
      these results to the cases of acute influenza. The other limitation is IAV
      diversity. It cannot be excluded that other subtypes of IAV could be associated
      to reproduction failure in pigs.

PMID- 24893657
TI  - Administration of angiotensin II and a bradykinin B2 receptor blocker in
      midpregnancy impairs gestational outcome in guinea pigs.
AB  - BACKGROUND: The opposing renin-angiotensin system (RAS) and kallikrein-kinin
      system (KKS) are upregulated in pregnancy and localize in the utero-placental
      unit. To test their participation as counter-regulators, circulating angiotensin
      II (AII) was exogenously elevated and the bradykinin B2 receptor (B2R) was
      antagonized in pregnant guinea-pigs. We hypothesized that disrupting the RAS/KKS
      balance during the period of maximal trophoblast invasion and placental
      development would provoke increased blood pressure, defective trophoblast
      invasion and a preeclampsia-like syndrome. METHODS: Pregnant guinea-pigs received
      subcutaneous infusions of AII (200 MUg/kg/day), the B2R antagonist Bradyzide
      (BDZ; 62.5 microg/kg/day), or both (AII + BDZ) from gestational day 20 to 34. Non
      pregnant cycling animals were included in a control group (C NP) or received AII
      + BDZ (AII + BDZ NP) during 14 days. Systolic blood pressure was determined
      during cycle in C NP, and on the last day of infusion, and 6 and 26 days
      thereafter in the remaining groups. Twenty six days after the infusions blood and
      urine were extracted, fetuses, placentas and kidneys were weighed, and
      trophoblast invasion of spiral arteries was defined in the utero-placental units
      by immunocytochemistry. RESULTS: Systolic blood pressure transiently rose in a
      subgroup of the pregnant females while receiving AII + BDZ infusion, but not in
      AII + BDZ NP. Plasma creatinine was higher in AII- and BDZ-treated dams, but no
      proteinuria or hyperuricemia were observed. Kidney weight increased in AII + BDZ
      treated pregnant and non-pregnant females. Aborted and dead fetuses were
      increased in dams that received AII and AII + BDZ. The fetal/placental weight
      ratio was reduced in litters of AII + BDZ-treated mothers. All groups that
      received interventions during pregnancy showed reduced replacement of endothelial
      cells by extravillous trophoblasts in lateral and myometrial spiral arteries.
      CONCLUSIONS: The acute effects on fetal viability, and the persistently impaired
      renal/placental sufficiency and incomplete arterial remodeling implicate the RAS
      and KKS in the adaptations in pregnancy. The results partially confirm our
      hypothesis, as a preeclampsia-like syndrome was not induced. We demonstrate the
      feasibility of characterizing systemic and local modifications in pregnant guinea
      pig, supporting its use to study normal placentation and related disorders.

PMID- 24893658
TI  - Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1alpha
      in hypoxia neonatal cardiomyocytes.
AB  - OBJECTIVE: To investigate whether ginsenoside-Rb1 (Gs-Rb1) inhibits the apoptosis
      of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the
      system is affected by hypoxia-induced factor 1alpha (Hif-1alpha). METHODS:
      Neonatal rat cardiomyocytes were randomly divided into 6 groups: a control group,
      a simple CoCl group, a simple Gs-Rb1 group, a CoCl and Gs-Rb1 hypoxia group, a
      CoCl and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) group, a CoCl and
      YC-1 group and a Gs-Rb1 group, in which YC-1 inhibits the synthesis and
      accelerates the degradation of Hif-1a. The concentration of CoCl, Gs-Rb1 and YC-1
      was 500 MUmol/L, 200 MUmol/L and 5 MUmol/L, respectively; the apoptosis ratio was
      analyzed with a flow cytometer; and apelin, APJ and Hif-1alpha were assayed with
      immunocytochemistry, Western blot assays and reverse transcription polymerase
      chain reaction (RT-PCR). RESULTS: (1) The anti-apoptosis effect of Gs-Rb1 on
      hypoxia cardiomyocytes was significantly inhibited by YC-1; (2) Hypoxia
      significantly up-graded the expression of mRNA and protein of apelin; this effect
      was further reinforced by Gs-Rb1 and significantly inhibited by YC-1; (3) Gs-Rb1
      further strengthened the expression of APJ mRNA and APJ proteins once hypoxia
      occurred, which was significantly inhibited by YC-1; (4) Gs-Rb1 significantly
      increased the expression of Hif-1alpha, which was completely abolished by YC-1;
      (5) There was a negative relationship between AR and apelin (or APJ, including
      mRNA and protein), a positive correlation between apelin (or APJ) protein and Hif
      1a protein, in hypoxia cardiomyocytes. CONCLUSION: The apelin-APJ system plays an
      important role in the anti-apoptosis effect of Gs-Rb1 on hypoxia neonatal
      cardiomyocytes, which was partly adjusted by Hif-1alpha.

PMID- 24893659
TI  - Inhibition of proprotein convertase subtilisin/kexin type 9: a novel mechanism of
      berberine and 8-hydroxy dihydroberberine against hyperlipidemia.
AB  - OBJECTIVE: To investigate the effect and molecular mechanisms of different doses
      of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in
      rats. METHODS: A rat model of hyperlipidemia was established by feeding rats a
      high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly
      selected as control group. The hyperlipidemic rats were then randomly divided
      into the following groups: a model group (MOD); a berberine group [BBR, 156
      mg/(kg day)]; Hdber groups, which were treated with different doses of Hdber [78,
      39 and 19.5 mg/(kg day)]; and a simvastatin group [SIM, 4 mg/(kg day)]. The
      corresponding therapy was administered to the rats of each treatment via gastric
      tubes. Normal animals were used as a control group. The blood levels of various
      lipids, including total cholesterol, triglycerides, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, free fatty acid (FFA),
      apolipoprotein AI(Apo-AI) and apolipoprotein B (Apo-B) were examined. The protein
      expressions of low-density lipoprotein receptor (LDL-R), sterol regulatory
      element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A
      reductase (HMGCR) and proprotein convertase subtilisin/kexin type 9 (PCSK-9) in
      liver tissues were determined by Western blot analysis. RESULTS: Compared with
      the control group of rats, the model group demonstrated a deteriorated blood
      lipid profile and exhibited increased expression levels of PCSK-9 protein in
      their liver tissues (P<0.01). In addition, the high-fat diet decreased the
      expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues.
      However, the addition of berberine or Hdber reversed the blood lipid profile
      changes (P<0.05 or P<0.01), decreased the expression levels of PCSK-9 proteins
      (P<0.01), and increased the expression levels of LDL-R proteins in the
      hyperlipidemic rats (P<0.01). These compounds did not significantly influence the
      expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats.
      CONCLUSIONS: Hdber is effective in the treatment of hyperlipidemia in rats. The
      therapeutic mechanisms of Hdber may be associated with increasing the expression
      of LDL-R protein and decreasing the expression of PCSK-9 protein in liver
      tissues.

PMID- 24893660
TI  - Occupational exposure to municipal solid wastes and development of toxic
      neuropathies: possible role of nutrient supplementation, complementary and
      alternative medicines in chemoprevention.
AB  - Achieving effective municipal solid waste (MSW) management remains a major
      challenge and waste generation and accumulation continue to constitute important
      environmental and public health concern, particularly in most developing
      countries. Although the general population is at risk of adverse health
      consequences and hazards associated with exposure to MSW, the waste management
      workers (WMWs) are the most vulnerable because of their direct involvement in the
      disposal of waste, with increasing evidence of work-related health and safety
      risks among these individuals. Among the numerous work-related health hazards
      prevalent in WMWs, development of toxic neuropathies following chronic
      occupational exposure remains poorly recognized. However, the risk or
      predisposition to toxic neuropathies is becoming evident considering the
      increasing recognition of large amount of neurotoxic heavy metals and hazardous
      industrial materials present in MSW in most parts of the world. The present
      review seeks to draw attention to the continuous vulnerability of the WMWs to
      developing toxic neuropathies. This is aimed at facilitating conscious efforts by
      relevant governmental and nongovernmental agencies towards promoting risk
      reduction and ensuring adequate protection against possible toxic
      polyneuropathies associated with occupational exposure to solid wastes. While
      continuous education of the WMWs on the need for adequate compliance to safety
      regulations and practice remains sacrosanct towards achieving significant
      reduction in toxic neuropathies and related adverse health consequences of waste
      handling, it is also our intention in this review to underscore the possible
      relevance of nutrient supplementation and alternative medicines in
      chemoprevention. 

PMID- 24893661
TI  - A bioeconomic model of a multi-site fishery with nonlinear demand function:
      number of sites optimizing the total catch.
AB  - We present a mathematical model of a fishery on several sites with a variable
      price. The model takes into account the evolution during the time of the
      resource, fish and boat movement between the different sites, fishing effort and
      price that varies with respect to supply and demand. We suppose that the
      movements of the boats and resource as well as the variation of the price go on
      at a fast time scale. We use methods of aggregation of variables in order to
      reduce the number of variables and we derive a reduced model governing two global
      variables, respectively the biomass of the resource and the fishing effort of the
      whole fishery. We look for the existence of equilibria of the aggregated model
      and perform local stability analysis. Two main cases can occur. The first one
      corresponds to over-exploitation leading to fish extinction. At extinction, the
      fishing effort tends to a positive value. The second case corresponds to a
      durable fishery equilibrium which is globally asymptotically stable. In the later
      case, we show that there exists a number of fishing sites that optimizes the
      total catch of the fishery. 

PMID- 24893662
TI  - Expression of threonine-biosynthetic genes in mammalian cells and transgenic
      mice.
AB  - Threonine is a nutritionally essential amino acid (EAA) for the growth and
      development of humans and other nonruminant animals and must be provided in diets
      to sustain life. The aim of this study was to synthesize threonine in mammalian
      cells through transgenic techniques. To achieve this goal, we combined the genes
      involved in bacterial threonine biosynthesis pathways into a single open reading
      frame separated by self-cleaving peptides (2A) and then linked it into a
      transposon system (piggyBac). The plasmids pEF1a-IRES-GFP-E2F-his and pEF1a-IRES
      GFP-M2F-his expressed Escherichia coli homoserine kinase and threonine synthase
      efficiently in mouse cells and enabled cells to synthesize threonine from
      homoserine. This biosynthetic pathway occurred with a low level of efficiency in
      transgenic mice. Three transgenic mice were identified by Southern blot from 72
      newborn mice, raising the possibility that a high level of expression of these
      genes in mouse embryos might be lethal. The results indicated that it is feasible
      to synthesize threonine in animal cells using genetic engineering technology.
      Further work is required to improve the efficiency of this method for introducing
      genes into mammals. We propose that the transgenic technology provides a
      promising means to enhance the synthesis of nutritionally EAAs in farm animals
      and to eliminate or reduce supplementation of these nutrients in diets for
      livestock, poultry and fish. 

PMID- 24893663
TI  - Cellular expression and localization of DGKzeta-interacting NAP1-like proteins in
      the brain and functional implications under hypoxic stress.
AB  - Diacylglycerol kinase (DGK) catalyzes conversion of a lipid second messenger
      diacylglycerol to another messenger molecule phosphatidic acid. Consequently, DGK
      plays a pivotal role in cellular pathophysiology by regulating the levels of
      these two messengers. We reported previously that DGKzeta translocates from the
      nucleus to cytoplasm in hippocampal neurons under ischemic/hypoxic stress. In
      addition, we also identified nucleosome assembly protein 1 (NAP1)-like proteins
      NAP1L1 and NAP1L4 as novel DGKzeta-interacting partners using a proteomic
      approach and revealed that these NAP1-like proteins induce cytoplasmic
      translocation of DGKzeta in overexpressed cells because NAP1-like proteins
      associate with the nuclear localization signal of DGKzeta and block its nuclear
      import via importin alpha. In the present study, we examined whether NAP1-like
      proteins are expressed in the brain and whether the molecular interaction of
      DGKzeta and NAP1-like proteins would be changed in the brain after hypoxic
      stress. Immunohistochemistry revealed that NAP1L1 and NAP1L4 are widely expressed
      in neurons and glial cells in the brain with some differences. After 3 days of
      transient whole-body hypoxic stress, DGKzeta translocated from the nucleus to
      cytoplasm in hippocampal pyramidal neurons, whereas NAP1-like proteins remained
      in the cytoplasm. Contrary to our expectations, NAP1-like proteins showed no
      change in their expression levels. The molecular interaction between DGKzeta and
      NAP1-like proteins was attenuated after hypoxic stress. These results suggest
      that DGKzeta cytoplasmic translocation in neurons under hypoxic stress is
      regulated by some mechanism which differs from that mediated by NAP1-like
      proteins.

PMID- 24893664
TI  - Identification and characterization of an ETHE1-like sulfur dioxygenase in
      extremely acidophilic Acidithiobacillus spp.
AB  - Elemental sulfur (S(0)) oxidation in Acidithiobacillus spp. is an important
      process in metal sulfide bioleaching. However, the gene that encodes the sulfur
      dioxygenase (SDO) for S(0) oxidation has remained unclarified in
      Acidithiobacillus spp. By BLASTP with the eukaryotic mitochondrial sulfur
      dioxygenases (ETHE1s), the putative sdo genes (AFE_0269 and ACAL_0790) were
      recovered from the genomes of Acidithiobacillus ferrooxidans ATCC 23270 and
      Acidithiobacillus caldus MTH-04. The purified recombinant proteins of AFE_0269
      and ACAL_0790 exhibited remarkable SDO activity at optimal mildly alkaline pH by
      using the GSH-dependent in vitro assay. Then, a sdo knockout mutant and a sdo
      overexpression strain of A. ferrooxidans ATCC 23270 were constructed and
      characterized. By overexpressing sdo in A. ferrooxidans ATCC 23270, a
      significantly increased transcriptional level of sdo (91-fold) and a 2.5-fold
      increase in SDO activity were observed when S(0) was used as sole energy source.
      The sdo knockout mutant of A. ferrooxidans displayed a slightly reduced growth
      capacity in S(0)-medium compared with the wild type but still maintained high
      S(0)-oxidizing activity, suggesting that there is at least one other S(0)
      oxidizing enzyme besides SDO in A. ferrooxidans ATCC 23270 cells. In addition, no
      obvious changes in transcriptional levels of selected genes related to sulfur
      oxidation was observed in response to the sdo overexpression or knockout in A.
      ferrooxidans when cultivated in S(0)-medium. All the results might suggest that
      SDO is involved in sulfide detoxification rather than bioenergetic S(0) oxidation
      in chemolithotrophic bacteria.

PMID- 24893665
TI  - Bacteria dominate the ammonia-oxidizing community in a hydrothermal vent site at
      the Mid-Atlantic Ridge of the South Atlantic Ocean.
AB  - Ammonia oxidation is the first and rate-limiting step of nitrification, which is
      carried out by two groups of microorganisms: ammonia-oxidizing bacteria (AOB) and
      the recently discovered ammonia-oxidizing archaea (AOA). In this study, diversity
      and abundance of AOB and AOA were investigated in five rock samples from a deep
      sea hydrothermal vent site at the Mid-Atlantic Ridge (MAR) of the South Atlantic
      Ocean. Both bacterial and archaeal ammonia monooxygenase subunit A (amoA) gene
      sequences obtained in this study were closely related to the sequences retrieved
      from deep-sea environments, indicating that AOB and AOA in this hydrothermal vent
      site showed typical deep ocean features. AOA were more diverse but less abundant
      than AOB. The ratios of AOA/AOB amoA gene abundance ranged from 1/3893 to 1/242
      in all investigate samples, indicating that bacteria may be the major members
      responding to the aerobic ammonia oxidation in this hydrothermal vent site.
      Furthermore, diversity and abundance of AOA and AOB were significantly correlated
      with the contents of total nitrogen and total sulfur in investigated samples,
      suggesting that these two environmental factors exert strong influences on
      distribution of ammonia oxidizers in deep-sea hydrothermal vent environment. 

PMID- 24893668
TI  - Abstracts of the XXIV European Congress of Perinatal Medicine, June 4-7, 2014,
      Florence, Italy.

PMID- 24893667
TI  - Do specific transitional patterns of antisocial behavior during adolescence
      increase risk for problems in young adulthood?
AB  - Latent transition analysis was used to identify patterns and trajectories of
      antisocial behavior (ASB) and their association with young adult outcomes in a
      nationally representative sample of adolescents (N = 5,422; 53.9% female).
      Participants were on average 13.96 years of age (SD = 1.06) at wave 1 of the
      study. Latent class analysis identified four classes of ASB including a non-ASB
      class, an aggressive class, a petty theft class, and a serious ASB class. In
      general, youth who were classified as serious stable ASB were the most at risk
      for problematic functioning in young adulthood. Youth who escalated to more
      serious patterns of ASB or reduced involvement also were at greater risk of
      negative outcomes in young adulthood compared to stable non-ASB youth, although
      they generally fared better than youth involved in stable patterns of more
      serious ASB. Gender differences indicated that involvement in ASB was a greater
      risk factor for alcohol use among boys and a greater risk factor for depression
      among girls in young adulthood. Results are discussed in terms of the predictive
      validity of classes of ASB to functioning in young adulthood and the implications
      of this research for prevention efforts.

PMID- 24893666
TI  - Gender-dependent aortic remodelling in patients with bicuspid aortic valve
      associated thoracic aortic aneurysm.
AB  - An aortic aneurysm is characterized by widening of the aortic lumen diameter with
      adverse remodelling of the vascular extracellular matrix. A thoracic aortic
      aneurysm (TAA) is highly prevalent in patients with a bicuspid aortic valve
      (BAV). We investigated the structural remodelling in the aneurysmal ascending
      aorta in correlation to molecular alterations in male versus female BAV-TAA
      patients. Aneurysmal aortic samples (diameter >4.4 cm) from male and female
      patients were compared to non-aneurysmal non-BAV samples. The diameter of the
      aneurysmal aorta was smaller in females but comparable to that of male patients
      when normalized to body mass index. Disorganized elastin fibres and reduced
      elastin protein were found in samples from males and females with BAV-TAA.
      However, disarrayed collagen fibres and reduced protein were detected only in
      aortas from males with BAV-TAA. Elastin and collagen I messenger RNA (mRNA)
      levels were comparable in the BAV-TAA and control groups of both genders,
      suggesting post-translation degradation. Total elastase activity was elevated
      similarly in both genders. The activity of MT1-MMP, a potent collagenase, was
      increased more in aortic samples from males than females with BAV-TAA samples.
      MMP8 and MMP13 were lower whereas MMP2 was higher in female compared to samples
      from male BAV-TAA group. TIMP3 and TIMP4 decreased similarly in both genders,
      while TIMP2 increased in the female BAV-TAA group. Lower smooth muscle cell
      density in the medial layer of aortas from males with BAV-TAA samples
      corresponded to the increased caspase-3 cleavage compared to that of females.
      CONCLUSION: We report a gender-dependent MMP/TIMP axis, collagen remodelling and
      smooth muscle cell (SMC) survival in the BAV-TAA aorta. The elevated TIMP2 could
      protect against the collagenolytic activity of MT1-MMP, leading to reduced
      collagen disarray and degradation in female BAV. KEY MESSAGE: More collagen
      degradation/disarray and smooth muscle cell loss in male BAV-TAA patients.
      Similar elastin degradation/disarray in the aneurysmal aorta of both genders.
      Reduced collagen and elastin in BAV-TAA due to enhanced degradation, not reduced
      synthesis. Elevated TIMP2 in female BAV-TAA aortas protects against collagen
      degradation by MT1-MMP.

PMID- 24893670
TI  - Adherence to hormone therapy among women with breast cancer.
AB  - BACKGROUND: Despite the excellent results obtained with hormone therapy, the long
      treatment period and the side effects associated with its use make patient
      adherence difficult. Moreover, certain aspects of health care can mitigate or
      exacerbate non-adherence. This study aimed to identify the factors associated
      with adherence to hormone therapy for breast cancer, with the goal of
      contributing to the reformulation of the care process and to improvements in
      outcomes. METHOD: This was a retrospective longitudinal study based on secondary
      data. The study integrated and analyzed data from a cohort of 5,861 women with
      breast cancer who were identified in the databases of the Brazilian National
      Cancer Institute [Instituto Nacional de Cancer - INCA] and the Unified Health
      System [Sistema Unico de Saude - SUS]. All of the patients were treated at INCA,
      which dispenses free medication, and the follow-up period lasted from 01/01/2004
      to 10/29/2010. The outcome of interest was hormone treatment adherence, which was
      defined as the possession of medication, and a logistic regression model was
      employed to identify the socio-demographic, behavioral, clinical, and health care
      variables that were independently associated with the variations in this outcome.
      RESULTS: The proportion of women who adhered to hormone therapy was 76.3%. The
      likelihood of adherence to hormone therapy increased with each additional year of
      age, as well as among women with a secondary or higher level education, those
      with a partner, those who underwent surgery, those who had more consultations
      with a breast specialist and clinical oncologist, and those who underwent
      psychotherapy; the effect for the latter increased with each additional
      consultation. Conversely, the likelihood of adherence was lower among patients at
      a non-curable stage, those who were alcohol drinkers, those who received
      chemotherapy, those who had undergone more tests and had more hospitalizations,
      and those who used tamoxifen and combined aromatase inhibitors. CONCLUSION: This
      study shows that approximately a quarter of the women with breast cancer did not
      adhere to hormone treatment, thus risking clinical responses below the expected
      standards. It also identifies the most vulnerable subgroups in the treatment
      process and the aspects of care that provide better results.

PMID- 24893671
TI  - Meta-analysis of prospective studies on the effects of nut consumption on
      hypertension and type 2 diabetes mellitus.
AB  - BACKGROUND: Inconclusive reports have been published on the consumption of nuts
      and the risk of hypertension and type 2 diabetes mellitus (T2DM). We performed a
      meta-analysis of prospective studies to assess the effects of nut consumption on
      hypertension and T2DM risks. METHODS: A PUBMED and EMBASE database search was
      performed. Summary relative risks (SRRs) and 95% confidence intervals (CIs) were
      calculated using a random-effects model. Q and I2 statistics were used to examine
      between-study heterogeneity. RESULTS: A total of eight articles with nine
      prospective cohort studies (three hypertension studies and six T2DM studies) were
      selected. Using random effects models, we found that compared with never/rare
      consumers of nuts, those consuming >2 servings per week had an 8% lower risk of
      hypertension (SRR = 0.92, 95% CI: 0.87-0.97, P(heterogeneity)  = 0.590, I2  =
      0%), while consumption of nuts at one serving per week had similar risk (SRR =
      0.97, 95% CI: 0.83-1.13). In addition, nuts consumption was not associated with
      risk of T2DM (SRRs = 0.98, 95% CI: 0.84-1.15; P(heterogeneity)  = 0.008, I2  =
      67.7%) on the basis of the highest versus lowest analysis. This null association
      was also shown in the dose-response analysis. CONCLUSION: Findings from this meta
      analysis indicate that consumption of nuts (>2 servings/week) may be inversely
      associated with hypertension risk, but not with T2DM risk.

PMID- 24893672
TI  - Editorial: overselling our findings.

PMID- 24893673
TI  - Sequential Diels-Alder reaction/rearrangement sequence: synthesis of
      functionalized bicyclo[2.2.1]heptane derivatives and revision of their relative
      configuration.
AB  - A sequential Diels-Alder reaction/rearrangement sequence was developed for the
      synthesis of diverse functionalized bicyclo[2.2.1]heptanes as novel floral and
      woody odorants. The outcome of the rearrangement depended on the substitution
      pattern of the dienes. 2D NMR analysis has established the correct relative
      configuration of the bicyclo[2.2.1]heptanone, which was originally misassigned.
      Furthermore, when the initiating DA reaction was catalyzed by a chiral Lewis
      acid, the bicyclo[2.2.1]heptane derivatives including (+)-herbanone can be
      obtained in an enantiomeric ratio (er) up to 96.5:3.5. 

PMID- 24893675
TI  - The race to close perimembranous ventricular septal defects (PVSD): proceed with
      caution.

PMID- 24893674
TI  - EBV & HHV6 reactivation is infrequent and not associated with MS clinical course.
AB  - BACKGROUND: Among the environmental factors associated with multiple sclerosis
      (MS) causation, some of the strongest associations are with Epstein-Barr virus
      (EBV), and to a lesser extent human herpesvirus 6 (HHV6). Associations with
      clinical course are less conclusive, however. METHODS: We evaluated serum anti
      EBV-EA-R IgG and anti-HHV6 IgM, and EBV and HHV6 viral load (VL) for their
      associations with relapse, disability, and progression in disability in a
      prospective cohort of 198 participants with clinically definite MS. RESULTS: Anti
      EBV-EA-R IgG was detected in 81.8% of cases at study entry, and titers remained
      essentially unchanged during the study. Anti-HHV6 IgM was detected in only one
      participant, and EBV-VL (29%) and HHV6-VL (1.8%) were detected in a minority of
      samples, and where detected levels were low. Our previously demonstrated
      association between anti-HHV6 IgG and relapse hazard was not affected by
      adjustment for parameters of reactivation. We found no evidence that any of the
      viral markers were associated with disability or progression in disability. In
      relation to relapse, only EBV-VL was positively associated, although this was
      strongly influenced by a single individual. CONCLUSION: Using a prospective
      cohort design, we found no convincing evidence that reactivation parameters of
      EBV or HHV6 were associated with subsequent MS relapse hazard or progression in
      disability, confirming previous findings, and indicating that herpesvirus
      reactivation is not an important driver of relapse or disability in this
      established MS population.

PMID- 24893676
TI  - Ultraviolet Erythematic Radiation dose received by golfers in winter, in
      Valencia.
AB  - This article analyzes Ultraviolet Erythematic Radiation (UVER) dose received by
      several golf players in winter in Valencia. Playing golf involves spending
      several hours outdoors because of the length of golf matches and training.
      Moreover, in Valencia there are many golf players coming from northern Europe,
      with a phototype very sensitive (I-II). For that reason, these people have an
      increasing risk while playing. This article shows that harmful effects coming
      from UVER radiation may occur not only in summer time but also in winter,
      especially at these latitudes. VioSpor dosimeters have been used to develop this
      analysis over several golf players on January 2013 between 10:00 h and 15:00 h,
      local time. 

PMID- 24893677
TI  - Highly interactive nature of flower-specific enhancers and promoters, and its
      potential impact on tissue-specific expression and engineering of multiple genes
      or agronomic traits.
AB  - Molecular stacking enables multiple traits to be effectively engineered in crops
      using a single vector. However, the co-existence of distinct plant promoters in
      the same transgenic unit might, like their mammalian counterparts, interfere with
      one another. In this study, we devised a novel approach to investigate enhancer
      promoter and promoter-promoter interactions in transgenic plants and demonstrated
      that three of four flower-specific enhancer/promoters were capable of distantly
      activating a pollen- and stigma-specific Pps promoter (fused to the cytotoxic DT
      A gene) in other tissues, as revealed by novel tissue ablation phenotypes in
      transgenic plants. The NtAGI1 enhancer exclusively activated stamen- and carpel
      specific DT-A expression, thus resulting in tissue ablation in an orientation
      independent manner; this activation was completely abolished by the insertion of
      an enhancer-blocking insulator (EXOB) between the NtAGI1 enhancer and Pps
      promoter. Similarly, AGL8 and AP1Lb1, but not AP1La, promoters also activated
      distinct tissue-specific DT-A expression and ablation, with the former causing
      global growth retardation and the latter ablating apical inflorescences. While
      the tissue specificity of the enhancer/promoters generally defined their
      activation specificities, the strength of their activity in particular tissues or
      developmental stages appeared to determine whether activation actually occurred.
      Our findings provide the first evidence that plant-derived enhancer/promoters can
      distantly interact/interfere with one another, which could pose potential
      problems for the tissue-specific engineering of multiple traits using a single
      vector stacking approach. Therefore, our work highlights the importance of
      adopting enhancer-blocking insulators in transformation vectors to minimize
      promoter-promoter interactions. The practical and fundamental significance of
      these findings will be discussed. 

PMID- 24893678
TI  - Feedback control as a framework for understanding tradeoffs in biology.
AB  - Control theory arose from a need to control synthetic systems. From regulating
      steam engines to tuning radios to devices capable of autonomous movement, it
      provided a formal mathematical basis for understanding the role of feedback in
      the stability (or change) of dynamical systems. It provides a framework for
      understanding any system with regulation via feedback, including biological ones
      such as regulatory gene networks, cellular metabolic systems, sensorimotor
      dynamics of moving animals, and even ecological or evolutionary dynamics of
      organisms and populations. Here, we focus on four case studies of the
      sensorimotor dynamics of animals, each of which involves the application of
      principles from control theory to probe stability and feedback in an organism's
      response to perturbations. We use examples from aquatic (two behaviors performed
      by electric fish), terrestrial (following of walls by cockroaches), and aerial
      environments (flight control by moths) to highlight how one can use control
      theory to understand the way feedback mechanisms interact with the physical
      dynamics of animals to determine their stability and response to sensory inputs
      and perturbations. Each case study is cast as a control problem with sensory
      input, neural processing, and motor dynamics, the output of which feeds back to
      the sensory inputs. Collectively, the interaction of these systems in a closed
      loop determines the behavior of the entire system. 

PMID- 24893679
TI  - Suprachiasmatic vasopressin and the circadian regulation of voluntary locomotor
      behavior.
AB  - A role for arginine vasopressin in the circadian regulation of voluntary
      locomotor behavior (wheel running activity) was investigated in the golden
      hamster, Mesocricetus auratus. Spontaneous nocturnal running was suppressed in a
      dose-dependent manner by systemic injections of vasopressin, and also in a
      concentration-dependent manner by microinjections directly into the hypothalamic
      suprachiasmatic nucleus. Pre-injections of a vasopressin V1 receptor antagonist
      into the nucleus reduced the suppression of behavior by vasopressin. Ethogram
      analyses revealed that peripheral drug injections predominantly increased
      grooming, flank marking, and sleep-related behaviors. Central injections did not
      induce sleep, but increased grooming and periods of 'quiet vigilance' (awake but
      not moving). Nocturnal behavioral profiles following either peripheral or central
      injections were similar to those shown by untreated animals in the hour prior to
      the onset of nocturnal wheel running. Site control vasopressin injections into
      the medial preoptic area or periaqueductal gray increased flank marking and
      grooming, but had no significant effect on locomotion, suggesting behavioral
      specificity of a vasopressin target near the suprachiasmatic nucleus. Both
      peripheral and central administration increased FOS-like immunoreactivity in the
      retinorecipient core of the suprachiasmatic nucleus. The distribution of FOS
      positive cells overlapped the calbindin subregion, but was more extensive, and
      most calbindin-positive cells did not co-express FOS. We propose a model of
      temporal behavioral regulation wherein voluntary behavior, such as nocturnal
      locomotor activity, is inhibited by the activity of neurons in the
      suprachiasmatic ventrolateral core that project to the posterior hypothalamus and
      are driven by rhythmic vasopressin input from the dorsomedial shell. 

PMID- 24893680
TI  - Cost-effectiveness of a community-based weight control intervention targeting a
      low-socioeconomic-status Mexican-origin population.
AB  - INTRODUCTION: The objective of our study was to evaluate the cost-effectiveness
      of a community-based intervention designed to improve physical activity levels
      and dietary intake and to reduce diabetes risk in a largely Hispanic population
      residing along the U.S.-Mexico border. METHOD: We forecasted disease outcomes,
      quality-adjusted life-years (QALYs) gained, and lifetime costs associated with
      actual and projected attainment of 2% and 5% weight loss taking a societal cost
      perspective. We extrapolated changes in beverage calorie consumption between
      baseline and 6-month follow-up to attain projected weight loss measures. Outcomes
      were projected 5, 10, and 20 years into the future and discounted at a 3.0% rate.
      RESULTS: The incremental cost-effectiveness ratio was $57,430 and $61,893,
      respectively, per QALY gained when compared with usual care for the 2% and 5%
      weight loss scenarios. The intervention was particularly cost-effective for
      morbidly obese participants. Cost-effectiveness improves when using 3-year weight
      loss projections based on changes in sugar-sweetened beverage caloric consumption
      to $49,478 and $24,092 for the 2% and 5% weight loss scenarios. CONCLUSIONS: This
      analysis demonstrates that a culturally sensitive community-based weight loss and
      maintenance intervention can be cost-effective even when healthy weight
      individuals participate.

PMID- 24893681
TI  - The 'Sharpen' filter improves the radiographic detection of vertical root
      fractures.
AB  - AIM: To compare the diagnostic accuracy of digital enhancement filters in the
      diagnosis of vertical root fractures. METHODOLOGY: The sample consisted of 40
      single-rooted teeth randomly divided into two groups: experimental and control.
      Vertical root fractures were induced in the experimental group using a universal
      testing machine. All teeth were individually radiographed with three different
      horizontal angles using the Digora Optime((r)) digital system. Three observers
      separately examined the original and filtered images (3D Emboss, Negative,
      Sharpen and Shadow). The area under Receiver Operating Characteristic curve
      values (Az) for each protocol were compared by one-way anova with post hoc
      Bonferroni test. The significance level was set at 5%. RESULTS: The highest Az
      value was obtained using the Sharpen filter, with significant differences from
      the original and other filtered images (P < 0.05). The 3D Emboss filter had the
      lowest Az value, which was significantly different from the other filtered images
      (P < 0.05). CONCLUSION: When using the Digora Optime((r)) system, the 'Sharpen'
      filter is recommended to improve the radiographic detection of vertical root
      fractures.

PMID- 24893682
TI  - Associations of maternal influences with outdoor play and screen time of two-year
      olds: Findings from the Healthy Beginnings Trial.
AB  - AIM: This study aims to investigate if maternal influences are associated with
      children's outdoor playtime and screen time at the age of 2 years. METHODS: A
      cross-sectional study with 497 first-time mothers and their children was
      conducted using the data from the Healthy Beginnings Trial undertaken in Sydney,
      Australia during 2007-2010. Maternal influences included their own physical
      activity and screen time, television rules for their child, perceived
      neighbourhood environment, parental self-efficacy and parenting style (warmth and
      hostility). Children's outdoor playtime, screen time and maternal influences were
      collected through face-to-face interviews with participating mothers when the
      children were 2 years old. Logistic regression analysis was conducted to examine
      the associations between maternal influences and children's outdoor play and
      screen time. RESULTS: Mothers with low levels of parental hostility and high
      perceived safe outdoor play environment were more likely to have children playing
      outdoor for >= 2 h/day with adjusted odds ratio (AOR) 2.65 (95% confidence
      interval (CI) 1.68-4.20, P < 0.0001) and AOR 2.44 (95% CI 1.85-3.85, P < 0.0001)
      respectively. Mothers' own screen time was the sole factor associated with
      children's screen time (AOR 1.90 (95% CI 1.29-2.81, P = 0.001)). CONCLUSION:
      Different maternal influences were independently associated with children's
      outdoor play or screen time at an early stage of life. Therefore, different
      intervention strategies are needed to increase children's outdoor playtime and
      decrease their screen time.

PMID- 24893683
TI  - Asp68His mutation in the A1 domain of human factor V causes impaired secretion
      and ineffective translocation.
AB  - Congenital factor V (FV) deficiency is a rare inherited disorder. We determined
      the mechanism of a missense mutation, Asp68His, in the A1 domain of the FV
      protein, is associated with severe FV deficiency. We characterized the mutant FV
      Asp68His protein using in vitro expression studies by using specific secretion
      and degradation pathway inhibitors and analysed the intracellular translocation
      of the mutant protein by immunofluorescence staining. The Asp68His mutation
      caused very low levels of FV protein in the conditioned media, with normal
      specific FV activity. Similar mRNA degradation rates between FV-wild-type (wt)
      and FV-Asp68His mRNA showed that the Asp68His mutation does not affect FV
      expression at the transcriptional level. A specific secretion pathway inhibitor,
      brefeldin A, was used to demonstrate that the lower efficiency of transport to
      the outside of the cell for FV-Asp68His mutant protein compared with that of the
      FV-wt protein. Furthermore, we showed that the Asp68His mutation resulted in
      increased intracellular degradation through a MG132-mediated proteasomal
      degradation pathway. In the transfected cell lysates, FV-wt protein had multiple
      posttranslational modified forms, but the FV-Asp68His protein was not completely
      glycosylated. We further observed that the FV-Asp68His protein was retrieved in
      the endoplasmic reticulum only and did not undergo transport to the Golgi
      apparatus, leading to impaired secretion. These results strongly suggest that the
      Asp68His mutation may result in intracellular defective trafficking and enhanced
      degradation, and impaired secretion of FV protein. 

PMID- 24893684
TI  - Baseline characteristics and management of patients with atrial
      fibrillation/flutter in the emergency department: results of a prospective,
      multicentre registry in China.
AB  - BACKGROUND/AIM: There have been several studies of atrial fibrillation (AF) over
      the past decades; however, data from Chinese patients are scarce. The aim of the
      study was therefore to describe the patient characteristics, risk profile and
      management strategies for Chinese AF patients presenting to emergency department
      (ED). METHODS: We conducted a prospective, multicentre registry of patients with
      AF or atrial flutter (AFL) in China. Participants were enrolled at 20 EDs, then
      data regarding baseline characteristics and treatment in EDs were collected.
      RESULTS: Of the 2016 Chinese patients, 1104 (54.8%) were female. Six hundred
      eighteen (30.7%) had paroxysmal AF, 452 (22.4%) had persistent AF and 945 (46.9%)
      had permanent AF. The most common comorbidity was hypertension (55.5%), followed
      by coronary artery disease (41.8%) and heart failure (HF, 37.4%). The prevalence
      of concomitant cardiovascular risk factors, such as HF and valvular heart
      disease, increased as AF progressed. Among the patients with non-valvular AF, 110
      (12.7%) of those with CHADS2 (congestive HF, hypertension, age of 75 years and
      greater, diabetes mellitus and history of stroke) >=2 were prescribed oral
      anticoagulants (OAC), while 119 (15.6%) of those with CHADS2 <2 received such
      agents. Among the 324 patients with valvular AF, 134 (41.4%) actually were
      treated with OAC. The international normalised ratio value was within the target
      range (2.0-3.0) in 96 patients only (26.4%). Moreover, a total of 16.2% of the
      patients received >=1 anti-arrhythmic agents, whereas rate control agents were
      used more frequently (68.4%). CONCLUSIONS: According to the present study, the
      risk profile and management of Chinese patients with AF/AFL differed from that
      observed in previous studies. The use of OAC inadequately deviate from current
      guidelines.

PMID- 24893685
TI  - Hepatocellular carcinoma in cirrhotic patients with transjugular intrahepatic
      portosystemic shunt: a retrospective case-control study.
AB  - BACKGROUND: An association between Transjugular Intrahepatic Porto-Systemic Shunt
      (TIPS) and the development of hepatocellular carcinoma in patients with cirrhosis
      has been suggested, but not confirmed. AIM: To evaluate the potential role of
      TIPS in hepatocellular carcinoma development. METHODS: We performed a
      retrospective case-control study among patients with cirrhosis; all cases had
      undergone TIPS placement. Cases and controls were followed as outpatients at a
      single liver care centre in the same timeframe. RESULTS: Overall, 101 patients
      with cirrhosis (mean age 58 +/- 9 years, 64.3% male) were included in each group.
      Median duration of follow-up was 56.7 months (range 8.2-174.5) for TIPS patients
      and 67.8 months (range 8.3-183.1) for controls (p=0.08). In both groups 94% of
      patients had Child-Pugh Class A or B cirrhosis. The cumulative incidence of
      hepatocellular carcinoma at 1, 3, 5, and 10 years was 2%, 7%, 18%, and 46% among
      TIPS patients, and 3%, 10%, 19%, and 39% among controls (log rank test p=0.19).
      Compared to controls, hepatocellular carcinoma nodules in TIPS patients were more
      frequently situated in the right lobe (p<0.05). CONCLUSIONS: TIPS does not seem
      to increase the risk of hepatocellular carcinoma in patients with Child-Pugh
      Class A or B cirrhosis; for these patients ultrasound surveillance should not be
      modified.

PMID- 24893686
TI  - Infliximab as a bridge to remission maintained by antimetabolite therapy in
      Crohn's disease: A retrospective study.
AB  - BACKGROUND: Infliximab withdrawal in patients with Crohn's disease on concomitant
      antimetabolite therapy is considered to be superior if obtained after a
      maintenance therapy period compared to induction alone. METHODS: We
      retrospectively analyzed the outcome of Crohn's disease patients treated with
      infliximab and an antimetabolite after infliximab was withdrawn using induction
      alone or induction plus at least 1-year of maintenance therapy. The time to
      relapse was analyzed using univariate and multivariate analyses. The model was
      adjusted according to the period of infliximab withdrawal. RESULTS: A total of 92
      patients were included, 54 in the induction alone group. The patient
      characteristics were identical in the two groups except for the period of
      infliximab withdrawal. After a median follow-up period of 47.1 (interquartile
      range=4.4-110.2) months, 66 patients (72%) experienced a relapse. After a year
      adjustment, no significant difference was observed between the two groups. Based
      on year-adjusted multivariate analysis, the risk factors for relapse were active
      smoking, previous antimetabolite failure, and perianal disease. After relapse, 53
      patients (80%) were retreated with infliximab. After infliximab retreatment,
      clinical remission was observed in 47 patients (89%) at weeks 8-10. CONCLUSION:
      In Crohn's disease patients, the probability of relapse on antimetabolite therapy
      after infliximab withdrawal was not superior after a 1-year scheduled maintenance
      therapy as compared with an induction alone.

PMID- 24893687
TI  - Authors' reply to comment on "self-expandable metal stents for malignant colonic
      obstruction: data from a retrospective regional SIED-AIGO study" by R. Di Mitri,
      F. Mocciaro, M. Traina et al. [Digestive and Liver Disease 2014;46:279-82].

PMID- 24893688
TI  - Long acting release-octreotide as "rescue" therapy to control angiodysplasia
      bleeding: A retrospective study of 98 cases.
AB  - BACKGROUND: Gastrointestinal angiodysplasias are an important cause of difficult
      to manage bleeding, especially in older patients. AIM: To retrospectively
      evaluate the long-term efficacy of long acting release-octreotide in controlling
      angiodysplasia bleeding. METHODS: 98 patients with a history of bleeding due to
      gastrointestinal angiodysplasias lasting over 2 years were retrospectively
      selected among those treated from January 2000 to December 2008. All patients had
      received octreotide 0.1mg tid for 28 days and, then from day 14, long acting
      release-octreotide 20mg monthly, for 6 months. RESULTS: The mean follow-up was 78
      months. In all patients mean haemoglobin levels significantly increased and the
      number of bleeding episodes, hospitalizations, patients requiring blood
      transfusions and units of transfused red cells significantly decreased, compared
      to the two-year observation period before starting therapy. According to outcome
      patients were classified as: 40 full responders (40.8%), 32 relapsers (32.6%) and
      26 poor responders (26.5%). At multivariate analysis age >65 years, male sex,
      chronic antiplatelet therapy, chronic obstructive pulmonary disease and chronic
      renal failure were the only covariates independently associated with poor
      response to therapy. CONCLUSION: Our study suggests that long acting release
      octreotide could be used as rescue therapy to control bleeding due to
      gastrointestinal angiodysplasias in patients not suitable for endoscopic or
      surgical treatments.

PMID- 24893689
TI  - Paradoxical reaction to midazolam in patients undergoing endoscopy under
      sedation: Incidence, risk factors and the effect of flumazenil.
AB  - BACKGROUND: The incidence, risk factors and management strategy of paradoxical
      reaction to midazolam during endoscopy are yet to be clarified. METHODS: This
      single center prospective study included 4140 adult patients (2263 males, mean
      age of 57.7 +/- 12.6) undergoing endoscopy under sedation with midazolam and
      pethidine between September 2011 and December 2011. The characteristics of
      patients with and without paradoxical reaction were compared. For patients who
      experienced paradoxical reaction and received flumazenil, their endoscopic images
      were reviewed to assess whether European Society of Gastrointestinal Endoscopy
      guidelines were met as quality indicator of endoscopy. RESULTS: The incidence of
      paradoxical reaction was 1.4%. In multivariate analyses, male gender,
      unsuccessful sedation in previous endoscopy, upper endoscopy, higher dose of
      midazolam, and lower dose of pethidine were identified as independent risk
      factors for paradoxical reaction. Despite paradoxical reaction, endoscopic
      procedures were successfully completed in 93.3% of cases when flumazenil was
      administered. The rates of meeting quality indicator of endoscopy were 92.3% in
      patients receiving flumazenil for paradoxical reaction and 97.6% in patients
      without paradoxical reaction. CONCLUSIONS: For patients with risk factors for
      paradoxical reaction, active use of pethidine with a dose reduction of midazolam
      might be helpful to prevent the occurrence of paradoxical reaction.
      Administration of flumazenil might be positively considered in cases of
      paradoxical reaction.

PMID- 24893690
TI  - Genetic characterisation of Neospora caninum strains from clinical samples of
      zebuine foetuses obtained in abattoirs in Goias, Brazil.
AB  - The Neospora caninum microsatellite markers were applied to clinical samples.
      Genotyping technology involving fluorescently labelled DNA fragment analysis was
      used in combination with DNA sequencing for markers with complex repetitive
      sequences. Nineteen DNA samples from 15 brains and four hearts of naturally
      infected non-aborted zebuine foetuses from abattoirs in Goias, Brazil. N. caninum
      had been detected in these foetuses by nested-PCR of the internal transcribed
      spacer-1 rRNA region, and the samples were analysed using these microsatellites.
      Seven complete or nearly complete allele profiles were obtained from six
      foetuses. Three distinct profiles of N. caninum were identified in a unique
      microregion (Meia Ponte) of Goias. Two alleles for the same marker were detected
      in a unique foetus that was probably infected with two different strains. A new
      allele for one of the microsatellites is described. The multilocus analysis
      performed here revealed a preliminary means of discriminating between individual
      strains according to their geographical origins. These are the first results that
      have been obtained regarding the molecular characterisation of strains of N.
      caninum from infected zebuine foetuses in South America and reveal for the first
      time that there are genotypic differences in the strains that are responsible for
      foetal transmission in zebuine foetuses. 

PMID- 24893691
TI  - Survival of Ascaris suum and Ascaridia galli eggs in liquid manure at different
      ammonia concentrations and temperatures.
AB  - Eggs of Ascaris suum from pigs are highly resistant and commonly used as a
      conservative indicator of pathogen inactivation during slurry storage. Eggs of
      Ascaridia galli, the poultry ascarid, are also known to be highly resistant but
      the suitability as an indicator of pathogen inactivation has never been tested.
      Pig slurry has to be stored for several months to inactivate pathogens but
      chemical treatment of slurry may reduce this time. The suitability of A. galli as
      an indicator of slurry sanitation was tested by comparing the survival of eggs of
      A. suum and A. galli in pig slurry. In addition, the effect of urea treatment on
      inactivation of ascarid eggs in relation to storage time was also tested. Nylon
      bags with 10,000 eggs of either species were placed in 200 ml plastic bottles
      containing either urea-treated (2%) or untreated pig slurry for up to 120 days at
      20 degrees C, 6 days at 30 degrees C, 36h at 40 degrees C or 2h at 50 degrees C.
      At all the temperatures in both slurry types, A. galli eggs were inactivated at a
      significantly faster rate (P<0.05) compared to A. suum eggs. For each 10 degrees
      C raise in temperature from 20 degrees C, T50 (time needed to inactivate 50% of
      eggs) for both types of eggs was reduced markedly. At all temperatures, viability
      of eggs of both species was significantly higher (P<0.05) in untreated slurry
      compared to urea-treated slurry except A. galli eggs at 20 degrees C where no
      significant difference was detected. In untreated slurry, the levels of pH (6.33
      9.08) and ammonia (0.01-1.74 mM) were lower (P<0.0001) compared to that of urea
      treated slurry (pH: 8.33-9.28 and ammonia 1-13 mM). The study demonstrated that
      A. galli eggs are more sensitive to unfavourable conditions compared to A. suum
      eggs. The use of A. galli eggs as hygiene indicator may thus be suitable to
      assess inactivation of pathogens that are more sensitive than A. galli eggs.
      Addition of urea may markedly reduce the storage time of slurry needed to
      inactivate A. suum and A. galli eggs.

PMID- 24893692
TI  - American Association of Veterinary Parasitologists' review of veterinary fecal
      flotation methods and factors influencing their accuracy and use--is there really
      one best technique?
AB  - The principle of fecal flotation is based on the ability of a solution to allow
      less dense material (including parasite elements) to rise to the top. However,
      there are numerous factors that will influence the accuracy and use of such a
      theoretically simple technique. Whether or not centrifugation is used appears to
      have an impact on the ability to detect some parasites, but not others. Using a
      flotation solution with a relatively high specific gravity favors the
      simultaneous flotation of the diagnostic stages of many different parasites
      while, at the same time, making recognition of some more difficult because of
      distortion as well as the amount of debris in the preparation. Dilution methods
      tend to be less accurate because they require extrapolation; however, they are
      quicker to perform, in part, because of the cleaner preparation. Timing is a
      critical factor in the success of all flotation methods, as is technical ability
      of the personnel involved. Thus, simplicity, low costs and time savings have
      generally favored gravitational flotation techniques (including the McMaster
      technique and its modifications). How accurate the method needs to be is
      dependent upon the purpose of its use and choice of method requires an
      understanding of analytical sensitivity and expected levels of egg excretion. In
      some instances where the difference between, for example, 0 and 50 eggs per gram
      is insignificant with regards to management decisions, less accurate methods will
      suffice. In others, where the presence of a parasite means treatment of the
      animal regardless of the numbers of eggs present, methods with higher analytical
      sensitivities will be required, particularly for those parasites that pass few
      eggs. For other uses, such as the Fecal Egg Count Reduction Test, accuracy may
      become critical. Therefore, even though recommendations for standardized fecal
      flotation procedures have been promoted in the past, it is clear that the factors
      are too numerous to allow for the recommendation of one, or even a few,
      procedures for all purposes. 

PMID- 24893693
TI  - Risk assessment for parasites in cultures of Diplodus puntazzo (Sparidae) in the
      Western Mediterranean: prospects of cross infection with Sparus aurata.
AB  - The sharpsnout seabream Diplodus puntazzo is of interest in Mediterranean fish
      farming. Disease is an important problem because parasites can spread quickly in
      culture conditions and fish often develop high parasite burdens. Here we assess
      the risk that documented parasites pose to the sustainability of D. puntazzo
      farming. This study specifically considers metazoan and protist parasites
      recorded from wild and farmed D. puntazzo in scientific literature. Risk
      assessment studies involve the identification, characterization and qualitative
      quantification of the risk in question (parasitoses in this case) and the
      probability of establishment. We considered the parasite species which may be
      difficult to manage as a priority for research into potential management
      strategies. Those parasites which could be transmitted from cultures of gilthead
      seabream (Sparus aurata) were also included in this study. Four groups of
      parasites represented a risk to D. puntazzo farming, ranging from moderate to
      high: Ciliophora, Myxozoa, Monogenea and Copepoda. Three parasite species were
      considered high risk to D. puntazzo cultures: Amyloodinium sp., Cryptocaryon sp.
      and Enteromyxum leei. These species were responsible for high mortalities in
      cultures of these and other fish species. In addition Sparicotyle chrysophrii,
      Caligus ligusticus and Gnathia vorax entail a moderate risk to D. puntazzo
      Mediterranean farms. No important episodes have been related to caligids and
      isopods in Mediterranean sparids, nevertheless they should be properly managed to
      prevent future problems. 

PMID- 24893695
TI  - Rhipicephalus rossicus and not R. sanguineus is the dominant tick species of dogs
      in the wetlands of the Danube Delta, Romania.
AB  - Changes in the distribution of tick species are among the major causes for the
      increase in prevalence of zoonotic diseases worldwide, with tick-borne diseases'
      prevalence showing an emerging pattern. One of these ticks, Rhipicephalus
      rossicus, which is reported occasionally from humans, seems to be particularly
      interesting because of its demonstrated vectorial role for zoonotic pathogens
      like Francisella tularensis, Coxiella burnetii, or CCHF and West Nile viruses.
      Here we report a case of dominant occurrence of R. rossicus on household dogs in
      the wetlands of Eastern Europe (Romania). Ticks were collected from dogs in 5
      distinct locations, with 1068 ticks of 6 species found. R. rossicus had a
      dominant occurrence in dogs in all but one location, accounting for 87.1% of all
      ticks (32.3-95.3% in different locations). Until this study, Rhipicephalus
      sanguineus was considered as the only important tick species on dogs in south
      temperate regions of Europe, as well in Romania. The dominant presence of R.
      rossicus in dogs, its vectorial competence and broad host spectrum (including
      humans), make this tick species an important candidate for further analysis and
      highlight the paucity of our knowledge on disease vectors in this region of
      Europe. 

PMID- 24893694
TI  - The association between landscape and climate and reported tick paralysis cases
      in dogs and cats in Australia.
AB  - The aim of this study was to describe the association between landscape and
      climate factors and the occurrence of tick paralysis cases in dogs and cats
      reported by veterinarians in Australia. Data were collated based on postcode of
      residence of the animal and the corresponding landscape (landcover and elevation)
      and climate (precipitation, temperature) information was derived. During the
      study period (October 2010-December 2012), a total of 5560 cases (4235 [76%]
      canine and 1325 [24%] feline cases) were reported from 341 postcodes, mostly
      along the eastern seaboard of Australia and from the states of New South Wales
      and Queensland. Significantly more cases were reported from postcodes which
      contained areas of broadleaved, evergreen tree coverage (P=0.0019); broadleaved,
      deciduous open tree coverage (P=0.0416); and water bodies (P=0.0394).
      Significantly fewer tick paralysis cases were reported from postcodes which
      contained areas of sparse herbaceous or sparse shrub coverage (P=0.0297) and
      areas that were cultivated and managed (P=0.0005). No significant (P=0.6998)
      correlation between number of tick paralysis cases reported per postcode and
      elevation was found. Strong positive correlations were found between number of
      cases reported per postcode and the annual minimum (rSP=0.9552, P<0.0001) and
      maximum (rSP=0.9075; P=0.0001) precipitation. Correlations between reported tick
      paralysis cases and temperature variables were much weaker than for
      precipitation, rSP<0.23. For maximum temperature, the strongest correlation
      between cases was found in winter (rSP=0.1877; P=0.0005) and for minimum
      temperature in autumn (rSP=0.2289: P<0.0001). Study findings suggest that tick
      paralysis cases are more likely to occur and be reported in certain eco-climatic
      zones, such as those with higher rainfall and containing tree cover and areas of
      water. Veterinarians and pet owners in these zones should be particularly alert
      for tick paralysis cases to maximize the benefits of early treatment, and to be
      vigilant to use chemical prophylaxis to reduce the risk of tick parasitism. 

PMID- 24893696
TI  - First detection of Leishmania infantum DNA within the brain of naturally infected
      dogs.
AB  - Visceral leishmaniasis is an anthropozoonosis caused by the protozoan Leishmania
      infantum (L. chagasi). In dogs, the disease presents with systemic
      manifestations, including neurological disorders. There are rare reports of the
      presence of the parasite in the central nervous system of infected dogs, and some
      evidences of inflammatory lesions and the breakdown of cerebral barriers have
      been described. The aim of this study was to investigate the presence of L.
      infantum DNA in five specific areas of the brains of 20 naturally infected dogs
      by real-time PCR. For the first time, the presence of parasite DNA was detected
      and quantified in the brains of naturally infected dogs, in all evaluated
      regions. These data provide strong evidence of the presence of the Leishmania
      parasite in the nervous milieu and contribute to a new perspective of the
      pathogenesis of visceral leishmaniasis. 

PMID- 24893697
TI  - Acute phase response in dogs with Dirofilaria immitis.
AB  - The aim of this study was to determine concentrations of different positive and
      negative acute phase proteins (C-reactive protein, haptoglobin, albumin and
      paraoxonase-1) in dogs naturally infected with Dirofilaria immitis at the time of
      diagnosis. 194 dogs were included in the study. All were evaluated for the
      presence or absence of D. immitis circulating antigens and for the presence or
      absence of microfilariae and a clinical examination was carried out. 38 dogs were
      negative and 156 dogs were positive for circulating D. immitis antigens. A
      significant increase in C-reactive protein and significant decreases in albumin
      and paraoxonase-1 activity were observed in positive dogs. These changes appeared
      with independence of the presence/absence of microfilariae or clinical signs. C
      reactive protein was the only acute phase protein that showed significant
      differences between asymptomatic and symptomatic dogs. Interestingly, the
      increases seen in C-reactive protein values were not accompanied by increases in
      haptoglobin, and haptoglobin even decreased in the dogs with microfilaria. This
      could be due to the hemolytic anemia which can be produced in dirofilariasis. In
      conclusion, there is an acute phase response (with increases in C-reactive
      protein and decreases in albumin and paraoxonase-1) and a divergence in the
      behaviour between C-reactive protein and haptoglobin in dogs with D. immitis. 

PMID- 24893698
TI  - Moisture requirements for the migration of Haemonchus contortus third stage
      larvae out of faeces.
AB  - The abomasal nematode Haemonchus contortus causes severe disease and production
      loss in small ruminants in warmer regions and is also an emerging threat in many
      temperate climates. Specific knowledge of the effects of climate on the
      epidemiology of H. contortus is needed to effectively apply sustainable control
      strategies, which rely on prediction of infection risk. Although the effects of
      temperature and rainfall on larval development in this species have been
      characterised, much less is known about migration out of faeces and onto herbage.
      This is an important deficit in our understanding of the epidemiology of
      haemonchosis in regions with relatively low and particularly erratic rainfall.
      Methods were developed to assess the migration of third stage larvae (L3) out of
      faeces under simulated rainfall in the laboratory. These were applied in a series
      of experiments, which showed that rainfall is required for migration. However, a
      single rainfall event was not sufficient for migration from faeces of which the
      crust has hardened after having been kept in dry conditions. Light and regular
      rainfall resulted in rapid emergence from moist faeces kept in humid conditions,
      but much slower emergence from dry faeces in dry conditions. Ambient relative
      humidity therefore appears to act through faecal moisture content to modify the
      effect of rainfall on larval migration. Larvae survived well in dry faeces for a
      number of days, but did not migrate in the absence of rainfall, so sheep faeces
      could potentially act as a larval reservoir in dry conditions, with peaks of
      infection following rainfall. Rates of faecal desiccation and rehydration on
      pasture could therefore be highly relevant to temporal patterns of larval
      availability. 

PMID- 24893700
TI  - Lesch-Nyhan disease with no HPRT1 gene mutation?

PMID- 24893699
TI  - Preoperative prostate-specific antigen isoform p2PSA <= 22.5 pg/ml predicts
      advanced prostate cancer in patients undergoing radical prostatectomy.
AB  - BACKGROUND: The prediction value of prostate-specific antigen (PSA) isoform [
      2]proPSA (p2PSA) for detecting advanced prostate cancer (PCa) remains unclear.
      Our objective was to evaluate the additional clinical utility of p2PSA compared
      with total PSA (tPSA), free PSA (fPSA), and preoperative Gleason score (Gls) in
      predicting locally advanced PCa (pT3/T4) with high-accuracy discrimination. The
      aim was to develop a novel classification based on p2PSA and preoperative Gls for
      predicting advanced PCa. MATERIALS AND METHODS: In 208 consecutive men diagnosed
      with clinically localized PCa who underwent radical prostatectomy, we determined
      the predictive and discriminatory accuracy of serum tPSA, fPSA, percentage of
      fPSA to tPSA, p2PSA, p2PSA density, percentage of p2PSA to fPSA, and the Prostate
      Health Index. The cutoff level of p2PSA with best accuracy was estimated. The
      novel classification was developed by analyzing the interaction between p2PSA and
      Gls in predicting pathologic outcomes using a chi-square automatic interaction
      detection analysis. Decision curve analysis was applied to test the clinical
      consequences of using the novel classification. RESULTS: On univariate analyses,
      p2PSA, p2PSA density, percentage of p2PSA to fPSA, and Prostate Health Index were
      accurate but were not independent predictors by multivariate analysis. The p2PSA
      cutoff level of 22.5 pg/ml showed the best accuracy level for predicting and
      discriminating advanced diseases (area under the curve [AUC] = 0.725, sensitivity
      = 51.4%, specificity = 81.8%). By chi-square automatic interaction detection,
      univariate and multivariate analysis, a p2PSA level > 22.5 pg/ml was
      significantly associated with an increased frequency and risk of advanced
      disease. In patients with a p2PSA level <= 22.5 pg/ml, 91.8% of Gleason sum 6 PCa
      was organ confined. The combination of p2PSA and Gls enhanced slightly but
      significantly the predictive and discriminatory accuracy for advanced disease
      (0.6%-3.6%). CONCLUSIONS: The p2PSA cutoff level of 22.5 pg/ml can accurately
      discriminate between organ-confined and advanced PCa. The additional use of p2PSA
      enhanced slightly the predictive accuracy for advanced PCa (pT3/pT4) and has
      limited additional predictive value in identifying aggressive PCa (Gls > 7a).

PMID- 24893702
TI  - Interleukin 17A rs3819024 A>G polymorphism is associated with an increased risk
      of gastric cardia adenocarcinoma in a Chinese population.
AB  - Gastric cardia adenocarcinoma (GCA) is one of the most common malignant tumors.
      In addition to environmental risk factors, genetic factors might play an
      important role in GCA carcinogenesis. To evaluate the association between
      polymorphisms in the interleukin 17A (IL17A) gene on the development of GCA, we
      conducted a hospital-based case-control study. A total of 243 GCA cases and 476
      controls were recruited and their genotypes were determined using a custom-by
      design 48-Plex SNPscanTM Kit. IL17A rs3819024 A > G polymorphism was found to be
      associated with the increased risk of GCA. When the IL17A rs3819024 AA homozygote
      genotype was used as the reference group, the AG genotype was associated with a
      significantly increased risk of GCA (AG versus AA: adjusted OR = 1.53, 95% CI =
      1.05-2.23, p = 0.026). However, there was no significant association between five
      other SNPs and GCA. Stratified analyses indicated that a significantly increased
      risk of GCA associated with the IL17A rs3819024 A > G polymorphism was evident
      among male patients, patients who drank alcohol or those who never smoked. These
      findings indicated that functional polymorphism IL17A rs3819024 A > G might
      contribute to GCA susceptibility. Future larger studies with more rigorous study
      designs are required to confirm the current findings.

PMID- 24893701
TI  - A novel GPR30 rs10235056 A>G polymorphism associated with post-transcriptional
      regulation in lymphoblastoid cell lines.
AB  - Considering the role of variants in the 3' untranslated region (3'UTR) of GPR30
      gene remains unclear, we analyzed the association between the variants at the
      GPR30 gene 3'UTR miRNA binding sites and their mRNA expression using the data
      from the HapMap online database. Nine single nucleotide polymorphisms (SNPs) in
      GPR30 gene 3'UTR had available minor allele frequency (MAF) values which were
      obtained. And the frequency distribution of all the selected GPR30 gene 3'UTR
      variants genotypes among the different populations and pairwise linkage
      disequilibrium (LD) values were calculated. In addition, correlation analysis of
      the selected GPR30 variants genotypes and their mRNA expression in the
      lymphoblastoid cell lines was performed, which showed that only rs10235056 was
      significantly associated with GPR30 mRNA expression (p = 0.028), but rs4266553 (p
      = 0.304), rs3808353 (p = 0.900), rs3808354 (p = 0.739) and rs1133043 (p = 0.913)
      were insignificant. Taken together, the present study provides the first
      evidences that the GPR30 rs10235056 A > G polymorphism could be a putative
      variant mediating its post-transcriptional regulation, which might support its
      use as markers of cancer risk and individualized treatment.

PMID- 24893703
TI  - Feeder-free derivation of neural crest progenitor cells from human pluripotent
      stem cells.
AB  - Human pluripotent stem cells (hPSCs) have great potential for studying human
      embryonic development, for modeling human diseases in the dish and as a source of
      transplantable cells for regenerative applications after disease or accidents.
      Neural crest (NC) cells are the precursors for a large variety of adult somatic
      cells, such as cells from the peripheral nervous system and glia, melanocytes and
      mesenchymal cells. They are a valuable source of cells to study aspects of human
      embryonic development, including cell fate specification and migration. Further
      differentiation of NC progenitor cells into terminally differentiated cell types
      offers the possibility to model human diseases in vitro, investigate disease
      mechanisms and generate cells for regenerative medicine. This article presents
      the adaptation of a currently available in vitro differentiation protocol for the
      derivation of NC cells from hPSCs. This new protocol requires 18 days of
      differentiation, is feeder-free, easily scalable and highly reproducible among
      human embryonic stem cell (hESC) lines as well as human induced pluripotent stem
      cell (hiPSC) lines. Both old and new protocols yield NC cells of equal identity.

PMID- 24893705
TI  - Do mothers living in greener neighbourhoods have healthier babies?

PMID- 24893704
TI  - Maternal occupational exposure to polycyclic aromatic hydrocarbons and small for
      gestational age offspring.
AB  - OBJECTIVES: While some of the highest maternal exposures to polycyclic aromatic
      hydrocarbons (PAHs) occur in the workplace, there is only one previous study of
      occupational PAH exposure and adverse pregnancy outcomes. We sought to extend
      this literature using interview data combined with detailed exposure assessment.
      METHODS: Data for 1997-2002 were analysed from mothers of infants without major
      birth defects in the National Birth Defects Prevention Study, a large population
      based case-control study in the USA. Maternal telephone interviews yielded
      information on jobs held in the month before conception through delivery. From
      6252 eligible control mothers, 2803 completed the interview, had a job, met other
      selection criteria, and were included in the analysis. Two industrial hygienists
      independently assessed occupational exposure to PAHs from the interview and
      reviewed results with a third to reach consensus. Small for gestational age (SGA)
      was the only adverse pregnancy outcome with enough exposed cases to yield
      meaningful results. Logistic regression estimated crude and adjusted ORs.
      RESULTS: Of the 2803 mothers, 221 (7.9%) had infants who were SGA. Occupational
      PAH exposure was found for 17 (7.7%) of the mothers with SGA offspring and 102
      (4.0%) of the remaining mothers. Almost half the jobs with exposure were related
      to food preparation and serving. After adjustment for maternal age, there was a
      significant association of occupational exposure with SGA (OR=2.2, 95% CI 1.3 to
      3.8). CONCLUSIONS: Maternal occupational exposure to PAHs was found to be
      associated with increased risk of SGA offspring.

PMID- 24893706
TI  - Extracting visual evoked potentials from EEG data recorded during fMRI-guided
      transcranial magnetic stimulation.
AB  - Transcranial Magnetic Stimulation (TMS) is an effective method for establishing a
      causal link between a cortical area and cognitive/neurophysiological effects.
      Specifically, by creating a transient interference with the normal activity of a
      target region and measuring changes in an electrophysiological signal, we can
      establish a causal link between the stimulated brain area or network and the
      electrophysiological signal that we record. If target brain areas are
      functionally defined with prior fMRI scan, TMS could be used to link the fMRI
      activations with evoked potentials recorded. However, conducting such experiments
      presents significant technical challenges given the high amplitude artifacts
      introduced into the EEG signal by the magnetic pulse, and the difficulty to
      successfully target areas that were functionally defined by fMRI. Here we
      describe a methodology for combining these three common tools: TMS, EEG, and
      fMRI. We explain how to guide the stimulator's coil to the desired target area
      using anatomical or functional MRI data, how to record EEG during concurrent TMS,
      how to design an ERP study suitable for EEG-TMS combination and how to extract
      reliable ERP from the recorded data. We will provide representative results from
      a previously published study, in which fMRI-guided TMS was used concurrently with
      EEG to show that the face-selective N1 and the body-selective N1 component of the
      ERP are associated with distinct neural networks in extrastriate cortex. This
      method allows us to combine the high spatial resolution of fMRI with the high
      temporal resolution of TMS and EEG and therefore obtain a comprehensive
      understanding of the neural basis of various cognitive processes. 

PMID- 24893709
TI  - Body mass index and risk of death.

PMID- 24893707
TI  - Cerebrospinal fluid ceramides from patients with multiple sclerosis impair
      neuronal bioenergetics.
AB  - Axonal damage is a prominent cause of disability and yet its pathogenesis is
      incompletely understood. Using a xenogeneic system, here we define the
      bioenergetic changes induced in rat neurons by exposure to cerebrospinal fluid
      samples from patients with multiple sclerosis compared to control subjects. A
      first discovery cohort of cerebrospinal fluid from 13 patients with multiple
      sclerosis and 10 control subjects showed that acute exposure to cerebrospinal
      fluid from patients with multiple sclerosis induced oxidative stress and
      decreased expression of neuroprotective genes, while increasing expression of
      genes involved in lipid signalling and in the response to oxidative stress.
      Protracted exposure of neurons to stress led to neurotoxicity and bioenergetics
      failure after cerebrospinal fluid exposure and positively correlated with the
      levels of neurofilament light chain. These findings were validated using a second
      independent cohort of cerebrospinal fluid samples (eight patients with multiple
      sclerosis and eight control subjects), collected at a different centre. The toxic
      effect of cerebrospinal fluid on neurons was not attributable to differences in
      IgG content, glucose, lactate or glutamate levels or differences in cytokine
      levels. A lipidomic profiling approach led to the identification of increased
      levels of ceramide C16:0 and C24:0 in the cerebrospinal fluid from patients with
      multiple sclerosis. Exposure of cultured neurons to micelles composed of these
      ceramide species was sufficient to recapitulate the bioenergetic dysfunction and
      oxidative damage induced by exposure to cerebrospinal fluid from patients with
      multiple sclerosis. Therefore, our data suggest that C16:0 and C24:0 ceramides
      are enriched in the cerebrospinal fluid of patients with multiple sclerosis and
      are sufficient to induce neuronal mitochondrial dysfunction and axonal damage. 

PMID- 24893708
TI  - Targeting impulsivity in Parkinson's disease using atomoxetine.
AB  - Noradrenergic dysfunction may play a significant role in cognition in Parkinson's
      disease due to the early degeneration of the locus coeruleus. Converging evidence
      from patient and animal studies points to the role of noradrenaline in
      dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome,
      yet the direct effects of noradrenergic enhancement have not to date been
      addressed. Our aim was to directly investigate these, focusing on impulsivity
      during response inhibition and decision making. To this end, we administered 40
      mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with
      Parkinson's disease (12 female /13 male; 64.4 +/- 6.9 years old) in a double
      blind, randomized, placebo controlled design. Patients completed an extensive
      battery of neuropsychological tests addressing response inhibition, decision
      making, attention, planning and verbal short term memory. Atomoxetine improved
      stopping accuracy on the Stop Signal Task [F(1,19) = 4.51, P = 0.047] and reduced
      reflection impulsivity [F(1,9) = 7.86, P = 0.02] and risk taking [F(1,9) = 9.2, P
      = 0.01] in the context of gambling. The drug also conferred effects on
      performance as a function of its measured blood plasma concentration: it reduced
      reflection impulsivity during information sampling [adjusted R(2) = 0.23, F(1,16)
      = 5.83, P = 0.03] and improved problem solving on the One Touch Stockings of
      Cambridge [adjusted R(2) = 0.29, F(1,17) = 8.34, P = 0.01]. It also enhanced
      target sensitivity during sustained attention [F(1,9) = 5.33, P = 0.046]. The
      results of this exploratory study represent the basis of specific predictions in
      future investigations on the effects of atomoxetine in Parkinson's disease and
      support the hypothesis that targeting noradrenergic dysfunction may represent a
      new parallel avenue of therapy in some of the cognitive and behavioural deficits
      seen in the disorder. 

PMID- 24893710
TI  - Body mass index categories in observational studies of weight and risk of death.
AB  - The World Health Organization (Geneva, Switzerland) and the National Heart, Lung,
      and Blood Institute (Bethesda, Maryland) have developed standard categories of
      body mass index (BMI) (calculated as weight (kg)/height (m)(2)) of less than 18.5
      (underweight), 18.5-24.9 (normal weight), 25.0-29.9 (overweight), and 30.0 or
      more (obesity). Nevertheless, studies of BMI and the risk of death sometimes use
      nonstandard BMI categories that vary across studies. In a meta-analysis of 8
      large studies that used nonstandard BMI categories and were published between
      1999 and 2014 and included 5.8 million participants, hazard ratios tended to be
      small throughout the range of overweight and normal weight. Risks were similar
      between subjects of high-normal weight (BMI of approximately 23.0-24.9) and those
      of low overweight (BMI of approximately 25.0-27.4). In an example using national
      survey data, minor variations in the reference category affected hazard ratios.
      For example, choosing high-normal weight (BMI of 23.0-24.9) instead of standard
      normal weight (BMI of 18.5-24.9) as the reference category produced higher
      nonsignificant hazard ratios (1.05 vs. 0.97 for men and 1.06 vs. 1.02 for women)
      for the standard overweight category (BMI of 25.0-29.9). Use of the standard BMI
      groupings avoids problems of ad hoc and post hoc category selection and
      facilitates between-study comparisons. The ways in which BMI data are categorized
      and reported may shape inferences about the degree of risk for various BMI
      categories. 

PMID- 24893712
TI  - Invalid Controls Undermine Conclusions of FDA Studies.

PMID- 24893711
TI  - Lineage-reprogramming of pericyte-derived cells of the adult human brain into
      induced neurons.
AB  - Direct lineage-reprogramming of non-neuronal cells into induced neurons (iNs) may
      provide insights into the molecular mechanisms underlying neurogenesis and enable
      new strategies for in vitro modeling or repairing the diseased brain. Identifying
      brain-resident non-neuronal cell types amenable to direct conversion into iNs
      might allow for launching such an approach in situ, i.e. within the damaged brain
      tissue. Here we describe a protocol developed in the attempt of identifying cells
      derived from the adult human brain that fulfill this premise. This protocol
      involves: (1) the culturing of human cells from the cerebral cortex obtained from
      adult human brain biopsies; (2) the in vitro expansion (approximately requiring 2
      4 weeks) and characterization of the culture by immunocytochemistry and flow
      cytometry; (3) the enrichment by fluorescence-activated cell sorting (FACS) using
      anti-PDGF receptor-beta and anti-CD146 antibodies; (4) the retrovirus-mediated
      transduction with the neurogenic transcription factors sox2 and ascl1; (5) and
      finally the characterization of the resultant pericyte-derived induced neurons
      (PdiNs) by immunocytochemistry (14 days to 8 weeks following retroviral
      transduction). At this stage, iNs can be probed for their electrical properties
      by patch-clamp recording. This protocol provides a highly reproducible procedure
      for the in vitro lineage conversion of brain-resident pericytes into functional
      human iNs.

PMID- 24893713
TI  - Validation of a genomics-based hypothetical adverse outcome pathway: 2,4
      dinitrotoluene perturbs PPAR signaling thus impairing energy metabolism and
      exercise endurance.
AB  - 2,4-dinitrotoluene (2,4-DNT) is a nitroaromatic used in industrial dyes and
      explosives manufacturing processes that is found as a contaminant in the
      environment. Previous studies have implicated antagonism of PPARalpha signaling
      as a principal process affected by 2,4-DNT. Here, we test the hypothesis that 2,4
      DNT-induced perturbations in PPARalpha signaling and resultant downstream
      deficits in energy metabolism, especially from lipids, cause organism-level
      impacts on exercise endurance. PPAR nuclear activation bioassays demonstrated
      inhibition of PPARalpha signaling by 2,4-DNT whereas PPARgamma signaling
      increased. PPARalpha (-/-) and wild-type (WT) female mice were exposed for 14
      days to vehicle or 2,4-DNT (134 mg/kg/day) and performed a forced swim to
      exhaustion 1 day after the last dose. 2,4-DNT significantly decreased body
      weights and swim times in WTs, but effects were significantly mitigated in
      PPARalpha (-/-) mice. 2,4-DNT decreased transcript expression for genes
      downstream in the PPARalpha signaling pathway, principally genes involved in
      fatty acid transport. Results indicate that PPARgamma signaling increased
      resulting in enhanced cycling of lipid and carbohydrate substrates into
      glycolytic/gluconeogenic pathways favoring energy production versus storage in
      2,4-DNT-exposed WT and PPARalpha (-/-) mice. PPARalpha (-/-) mice appear to have
      compensated for the loss of PPARalpha by shifting energy metabolism to PPARalpha
      independent pathways resulting in lower sensitivity to 2,4-DNT when compared with
      WT mice. Our results validate 2,4-DNT-induced perturbation of PPARalpha signaling
      as the molecular initiating event for impaired energy metabolism, weight loss,
      and decreased exercise performance. 

PMID- 24893716
TI  - Expanded graphite as superior anode for sodium-ion batteries.
AB  - Graphite, as the most common anode for commercial Li-ion batteries, has been
      reported to have a very low capacity when used as a Na-ion battery anode. It is
      well known that electrochemical insertion of Na(+) into graphite is significantly
      hindered by the insufficient interlayer spacing. Here we report expanded graphite
      as a Na-ion battery anode. Prepared through a process of oxidation and partial
      reduction on graphite, expanded graphite has an enlarged interlayer lattice
      distance of 4.3 A yet retains an analogous long-range-ordered layered structure
      to graphite. In situ transmission electron microscopy has demonstrated that the
      Na-ion can be reversibly inserted into and extracted from expanded graphite.
      Galvanostatic studies show that expanded graphite can deliver a high reversible
      capacity of 284 mAh g(-1) at a current density of 20 mA g(-1), maintain a
      capacity of 184 mAh g(-1) at 100 mA g(-1), and retain 73.92% of its capacity
      after 2,000 cycles.

PMID- 24893715
TI  - Critical role of gamma-phosphate in structural transition of Na,K-ATPase upon ATP
      binding.
AB  - Active transport of sodium and potassium ions by Na,K-ATPase is accompanied by
      the enzyme conformational transition between E1 and E2 states. ATP and ADP bind
      to Na,K-ATPase in the E1 conformation with similar affinity but the properties of
      enzyme in complexes with these nucleotides are different. We have studied
      thermodynamics of Na,K-ATPase binding with adenine nucleotides at different
      temperatures using isothermal titration calorimetry. Our data indicate that beta
      phosphate is involved in complex formation by increasing the affinity of adenine
      nucleotides to Na,K-ATPase by an order of magnitude, while gamma-phosphate does
      not affect it. ATP binding to Na,K-ATPase in contrast to ADP binding generates a
      structural transition in the enzyme, which is consistent with the movement of a
      significant portion of the surface area to a solvent-protected state. We propose
      that ATP binding leads to convergence of the nucleotide-binding and
      phosphorylation domains transferring the enzyme from the "E1-open" to "E1-closed"
      conformation ready for phosphorylation. 

PMID- 24893714
TI  - Mice deficient in the gene for cytochrome P450 (CYP)1A1 are more susceptible than
      wild-type to hyperoxic lung injury: evidence for protective role of CYP1A1
      against oxidative stress.
AB  - Hyperoxia contributes to acute lung injury in diseases such as acute respiratory
      distress syndrome in adults and bronchopulmonary dysplasia in premature infants.
      Cytochrome P450 (CYP)1A1 has been shown to modulate hyperoxic lung injury. The
      mechanistic role(s) of CYP1A1 in hyperoxic lung injury in vivo is not known. In
      this investigation, we hypothesized that Cyp1a1(-/-) mice would be more
      susceptible to hyperoxic lung injury than wild-type (WT) mice, and that the
      protective role of CYP1A1 is in part due to CYP1A1-mediated decrease in the
      levels of reactive oxygen species-mediated lipid hydroperoxides, e.g., F2
      isoprostanes/isofurans, leading to attenuation of oxidative damage. Eight- to ten
      week-old male WT (C57BL/6J) or Cyp1a1(-/-) mice were exposed to hyperoxia (>95%
      O2) or room air for 24-72 h. The Cyp1a1(-/-) mice were more susceptible to oxygen
      mediated lung damage and inflammation than WT mice, as evidenced by increased
      lung weight/body weight ratio, lung injury, neutrophil infiltration, and
      augmented expression of IL-6. Hyperoxia for 24-48 h induced CYP1A expression at
      the mRNA, protein, and enzyme levels in liver and lung of WT mice. Pulmonary F2
      isoprostane and isofuran levels were elevated in WT mice after hyperoxia for 24
      h. On the other hand, Cyp1a1(-/-) mice showed higher levels after 48-72 h of
      hyperoxia exposure compared to WT mice. Our results support the hypothesis that
      CYP1A1 protects against hyperoxic lung injury by decreasing oxidative stress.
      Future research could lead to the development of novel strategies for prevention
      and/or treatment of acute lung injury. 

PMID- 24893717
TI  - Genetic architecture of rind penetrometer resistance in two maize recombinant
      inbred line populations.
AB  - BACKGROUND: Maize (Zea Mays L.) is one of the most important cereal crops
      worldwide and provides food for billions of people. Stalk lodging can greatly
      undermine the standability of maize plants and therefore decrease crop yields.
      Rind penetrometer resistance is an effective and reliable method for evaluating
      maize stalk strength, which is highly correlated with stalk lodging resistance.
      In this study, two recombinant inbred line populations were constructed from
      crosses between the H127R and Chang7-2 lines, and between the B73 and By804
      lines. We genotyped these two populations and their parents using 3,072 single
      nucleotide polymorphism markers and performed phenotypic assessment of rind
      penetrometer resistance in multiple environments to dissect the genetic
      architecture of rind penetrometer resistance in maize. RESULTS: Based on two
      linkage maps of 1,397.1 and 1,600.4 cM with average interval of 1.7 and 2.1 cM
      between adjacent makers, respectively, seven quantitative trait loci (QTL) for
      rind penetrometer resistance were detected in the two recombinant inbred line
      populations. These QTL were distributed in seven genomic regions, and each
      accounted for 4.4-18.9% of the rind penetrometer resistance variation. The QTL
      with the largest effect on rind penetrometer resistance, qRPR3-1, was located on
      chromosome 3 with the flanking markers PZE-103123325 and SYN23245. This locus was
      further narrowed down to a 3.1-Mb interval by haplotype analysis using high
      density markers in the target region. Within this interval, four genes associated
      with the biosynthesis of cell wall components were considered as potential
      candidate genes for the rind penetrometer resistance effect. CONCLUSIONS: The
      inheritance of rind penetrometer resistance is rather complex. A few large-effect
      quantitative trait loci, together with a several minor-effect QTL, contributed to
      the phenotypic variation in rind penetrometer resistance in the two recombinant
      inbred line populations that were examined. A potential approach for improving
      stalk strength and crop yields in commercial maize lines may be to introgress
      favorable alleles of the locus that was found to have the largest effect on rind
      penetrometer resistance (qRPR3-1).

PMID- 24893718
TI  - An evaluation of long-term changes in alcohol use and alcohol problems among
      clients of the Swedish National Alcohol Helpline.
AB  - BACKGROUND: The Swedish National Alcohol Helpline was developed with the
      intention to provide an easily available, low threshold service to hazardous and
      harmful alcohol users in the community. The primary aim of this study was to
      describe the 12-month outcome of a cohort of clients and to evaluate whether
      these varied as a function of the intensity of exposure to the intervention.
      METHODS: The alcohol use and alcohol problems of a cohort of 191 clients
      accessing the service between 1 April 2009 and 1 February 2011 were assessed by
      telephone survey at the time of the first call and after 12 months. Change in
      AUDIT score between baseline and follow-up was used as primary outcome. Intensity
      of exposure was defined by number of counselling sessions. RESULTS: At 12-month
      follow-up, respondents had significantly reduced their AUDIT score to half of the
      baseline values, and one third of the participants were abstinent or consumed
      alcohol at a low-risk level. Participating in more than one counselling session
      as compared to one session was associated with a tendency to shift to a lower
      AUDIT zone at follow-up among women. CONCLUSIONS: The Alcohol Helpline provides a
      viable community service for harmful and hazardous alcohol users. Future
      randomized studies including other treatment or control conditions are warranted
      in order to strengthen our preliminary conclusion of possible effectiveness of
      the counselling provided at the helpline, as well as to explore further the role
      of gender in moderating the treatment's effect.

PMID- 24893721
TI  - Advances in implant dentistry.

PMID- 24893719
TI  - The associations between objectively-determined and self-reported urban form
      characteristics and neighborhood-based walking in adults.
AB  - BACKGROUND: Self-reported and objectively-determined neighborhood built
      characteristics are associated with physical activity, yet little is known about
      their combined influence on walking. This study: 1) compared self-reported
      measures of the neighborhood built environment between objectively-determined
      low, medium, and high walkable neighborhoods; 2) estimated the relative
      associations between self-reported and objectively-determined neighborhood
      characteristics and walking and; 3) examined the extent to which the objectively
      determined built environment moderates the association between self-reported
      measures of the neighborhood built environment and walking. METHODS: A random
      cross-section of 1875 Canadian adults completed a telephone-interview and postal
      questionnaire capturing neighborhood walkability, neighborhood-based walking,
      socio-demographic characteristics, walking attitudes, and residential self
      selection. Walkability of each respondent's neighborhood was objectively
      determined (low [LW], medium [MW], and high walkable [HW]). Covariate-adjusted
      regression models estimated the associations between weekly participation and
      duration in transportation and recreational walking and self-reported and
      objectively-determined walkability. RESULTS: Compared with objectively-determined
      LW neighborhoods, respondents in HW neighborhoods positively perceived access to
      services, street connectivity, pedestrian infrastructure, and utilitarian and
      recreation destination mix, but negatively perceived motor vehicle traffic and
      crime related safety. Compared with residents of objectively-determined LW
      neighborhoods, residents of HW neighborhoods were more likely (p < .05) to
      participate in (odds ratio [OR] = 3.06), and spend more time, per week (193
      min/wk) transportation walking. Perceived access to services, street
      connectivity, motor vehicle safety, and mix of recreational destinations were
      also significantly associated with transportation walking. With regard to
      interactions, HW x utilitarian destination mix was positively associated with
      participation, HW x physical barriers and MW x pedestrian infrastructure were
      positively associated with minutes, and HW x safety from crime was negatively
      associated with minutes, of transportation walking. Neither neighborhood type nor
      its interactions with perceived measures of walkability were associated with
      recreational walking, although perceived aesthetics was associated with
      participation (OR = 1.18, p < .05). CONCLUSIONS: Objectively-determined and self
      reported built characteristics are associated with neighborhood-based
      transportation walking. The objectively-determined built environment might
      moderate associations between perceptions of walkability and neighborhood-based
      transportation walking. Interventions that target perceptions in addition to
      modifications to the neighborhood built environment could result in increases in
      physical activity among adults.

PMID- 24893720
TI  - Biomass and RRR-alpha-tocopherol production in Stichococcus bacillaris strain
      siva2011 in a balloon bioreactor.
AB  - BACKGROUND: Green microalgae represent a renewable natural source of vitamin E.
      Its most bioactive form is the naturally occurring RRR-alpha-tocopherol which is
      biosynthesized in photosynthetic organisms as a single stereoisomer. It is
      noteworthy that the natural and synthetic alpha-tocopherols are different
      biomolecular entities. This article focuses on RRR-alpha-tocopherol production in
      Stichococcus bacillaris strain siva2011 biomass in a bioreactor culture with
      methyl jasmonate (MeJa) elicitor. Additionally, a nonlinear mathematical model
      was used to quantitatively scale-up and predict the biomass production in a 20 L
      balloon bioreactor with dual variables such as time and volume. RESULTS:
      Approximately 0.6 mg/g dry weight (DW) of RRR-alpha-tocopherol was enhanced in S.
      bacillaris strain siva2011 biomass with the MeJa 50 MUL/L for 24 hrs elicitations
      when compared to the control. The R2 value from the nonlinear model was enhanced
      up to 95% when compared to the linear model which significantly improved the
      accuracy for estimating S. bacillaris strain siva2011 biomass production in a
      balloon bioreactor. CONCLUSIONS: S. bacillaris strain siva2011 is a new green
      microalga which biosynthesizes significant amounts of RRR-alpha-tocopherol.
      Systematically validated dual variable empirical data should provide key insights
      to multivariable or fourth order modeling for algal biomass scale-up. This
      bioprocess engineering should provide valuable information for industrial
      production of RRR-alpha-tocopherol from green cells.

PMID- 24893722
TI  - The Tromso Study: Fit Futures: a study of Norwegian adolescents' lifestyle and
      bone health.
AB  - Bone mass achievement predicts later fracture risk. This population-based study
      describes bone mineral density (BMD) levels and associated factors in Norwegian
      adolescents. Compared with international reference ranges, BMD levels appear
      higher and physical activity levels are positively associated with BMD. PURPOSE:
      Norway has one of the highest reported incidences of osteoporotic fractures.
      Maximisation of peak bone mass may prevent later fractures. This population-based
      study compared BMD levels of Norwegian adolescents with international reference
      ranges and explored associated factors. METHODS: All first-year upper-secondary
      school students, aged 15-19 years in the Tromso region were invited to the Fit
      Futures study in 2010-2011. Over 90 % of the invited participants attended, 508
      girls and 530 boys. BMD was measured at total hip, femoral neck and total body by
      dual X-ray absorptiometry. Lifestyle variables were collected by self
      administered questionnaires and interviews. All analyses were performed sex
      stratified, using linear regression models. RESULTS: In girls, mean BMD (SD) was
      1.060 g/cm(2) (0.124), 1.066 g/cm(2) (0.123) and 1.142 g/cm(2) (0.077) at the
      total hip, femoral neck and total body, respectively. In boys, corresponding
      values were 1.116 (0.147), 1.103 (0.150) and 1.182 (0.097), with significant
      higher values than the Lunar pediatric reference at 16 years of age. In girls,
      height and self-reported intensive physical activity of more than 4 h a week and
      early sexual maturation were positively associated with BMD at both femoral sites
      (p < 0.047). Among boys age, height, body mass index, physical activity and
      alcohol intake were positively (p < 0.038), whereas early stages of sexual
      maturation and smoking was negatively (p < 0.047) related to BMD. CONCLUSIONS:
      Despite the heavy fracture burden, Norwegian adolescents' BMD levels are higher
      than age-matched Caucasians. Physical activity is associated with 1 SD increased
      BMD levels in those involved in competition or hard training.

PMID- 24893724
TI  - Painless transient bone marrow edema syndrome in a pediatric patient.
AB  - Transient regional migratory osteoporosis, considered to be part of the spectrum
      of bone marrow edema syndrome, is a rare condition with an unknown etiology.
      Patients usually present with lower extremity pain, most commonly in the 4th-5th
      decades of life. We describe a 15-year-old male patient with type 1 Gaucher
      disease who presented with transient bone marrow edema syndrome with features
      most closely resembling regional migratory osteoporosis. The patient presented
      with bone marrow edema of the lateral tibial epiphysis of his right knee that was
      incidentally seen on routine surveillance MRI that was performed as protocol for
      patients with type 1 Gaucher disease on enzyme replacement therapy. At this time,
      the patient had no pain and physical examination was normal. Follow-up MRI of the
      right knee 4 months afterward showed complete resolution of the signal
      abnormality in the right tibial epiphysis, and repeat study 8 months later
      displayed a new focus of painless migratory edema of the medial tibial epiphysis
      of the same knee. These changes completely resolved as well. Marrow signal
      abnormalities in children with Gaucher disease can have a broad differential,
      including infection, marrow infiltration, trauma, osteonecrosis, and bone marrow
      edema syndrome, amongst others. Correct diagnosis of bone marrow edema syndrome
      is critical, as this disease process most often resolves on conservative
      measures. The unusual presentation of transient bone marrow edema syndrome with
      regional migratory osteoporosis features in a young patient with Gaucher disease
      is described.

PMID- 24893723
TI  - Surgical resection techniques for locally advanced hilar cholangiocarcinoma.
AB  - BACKGROUND: Resection of perihilar cholangiocarcinoma involves major hepatectomy
      including caudate lobectomy. It is technically challenging because of the
      complex, intimate and variable relationship between biliary and vascular
      structures in the liver hilum. Resectability rates vary from 30 to 80 % and about
      one third of patients have microscopically involved margins. However, adequately
      performed resections provide 5-year survival of 30-40 % and are worth pursuing.
      PURPOSE: Better understanding of anatomy, better imaging, improved surgical
      techniques and progress in perioperative care of these patients have pushed the
      limits of resection of these tumours. Many of the traditional indicators of
      inoperability such as bilateral involvement of second-order hepatic ducts,
      contralateral biliary and vascular involvement, and need for arterial resection
      have been overcome or are being challenged. This review discusses techniques that
      may increase margin-free resectability of Bismuth-Corlette type III and IV
      perihilar cholangiocarcinoma. CONCLUSION: Advanced perihilar cholangiocarcinoma
      requires extended liver resection and often vascular resection, despite which the
      margin may be compromised in about one third of patients. Right sided tumours are
      likely to need right trisectionectomy and portal vein resection, best served by
      an en bloc hilar resection or Rex-recess approach. Left-sided tumours often
      involve contralateral blood vessels and require left trisegmentectomy with
      possible right portal vein or right hepatic artery reconstruction. These tumours
      are best tackled by hepatobiliary surgeons with experience in microvascular
      techniques. Salvage procedures when arterial reconstruction is not feasible are
      still under evaluation.

PMID- 24893726
TI  - [Consequences of uncritical indication assessment for hardware removal].
AB  - A 43-year-old woman sustained a severe ankle dislocation with distal fibular
      fracture in a domestic accident. This was initially treated with external
      fixation for 3 weeks. In addition to distal fibular fracture treatment using a
      fixed-angle locking plate system, a vacuum-assisted wound closure of the medial
      und lateral malleolus had to be performed due to a persisting difficult soft
      tissue situation with swelling and necrosis of the medial malleolus.
      Subsequently, after prolonged wound healing the soft tissue defect over the
      distal fibula could be covered with a split skin graft and the external fixation
      was removed. Implant removal was performed 2 years after primary treatment -
      following radiologically confirmed consolidation of the fracture.
      Intraoperatively, an iatrogenic oblique fracture of the fibula occurred due to a
      cold welded screw in the plate, which had to be treated with lag screws. In the
      further course, there was renewed extensive wound healing with methicillin
      resistant Staphylococcus aureus (MRSA) infection. The patient filed a complaint
      for the iatrogenic fibular fracture during hardware removal and also criticized
      the insufficient wound closure which led to an impairment of wound healing. The
      expert opinion of the arbitration board ascertained a medical malpractice in
      terms of indications. Due to the already prolonged course after the primary
      osteosynthesis hardware removal was not recommended. In addition, the surgical
      technique that led to the iatrogenic fracture was criticized. The arbitration
      board furthermore concluded that with a pre-existing osteoarthritis of the ankle,
      hardware removal was not indicated. In a critical wound situation implant removal
      would only be indicated with simultaneous treatment of the osteoarthritis of the
      ankle. By means of a critical indication assessment the patient should have been
      advised to leave the plate in place and the complicated course with iatrogenic
      fracture and severely delayed wound healing could have been avoided.

PMID- 24893725
TI  - [Ligament bracing--augmented cruciate ligament sutures: biomechanical studies of
      a new treatment concept].
AB  - BACKGROUND: In the context of acute knee dislocations, suture repair of ruptured
      cruciate ligaments leads to good clinical results in 80% of cases. Disadvantages
      are low primary stability and subsequently secondary elongation of the sutured
      ligaments. In the present study, we compared primary stability of suture repair,
      reinforced by different suture augments, to cruciate ligament reconstruction.
      OBJECTIVE: The concept of ligament bracing with transosseous suture repair of the
      cruciate ligaments and additional suture augmentation is biomechanically superior
      to cruciate ligament reconstruction. MATERIAL AND METHODS: A total of 42 porcine
      knee joints divided into seven groups were examined. The stability of four
      different suture/augmentation combinations were compared to cruciate ligament
      reconstruction with human hamstring tendons. The investigational setup consisted
      of testing 1000 cycles with 20 N to 154 N load in a.-p. translation and 60
      degrees  flexion. Elongation and load to failure were measured. RESULTS: Neither
      reconstruction (3.13 +/- 1.65 mm; 362 +/- 51 N) nor augmented suture repair (1.89
      2.5 mm; 464-624 N) achieved the primary stability of the intact cruciate ligament
      (0.63 +/- 0.34 mm, 1012 +/- 91 N). In comparison to ligament reconstruction, all
      four augmented suture repairs showed minor elongation in the cyclic test and a
      higher load to failure. The isolated suture repair showed poor results (6.79 +/-
      4.86 mm, 177 +/- 73 N). CONCLUSION: Augmented suture repair provides
      significantly higher stability compared with isolated suture repair and
      reconstruction with hamstring tendons. The concept of ligament bracing could be a
      promising future treatment option in acute knee dislocations. Clinical results
      remain to be seen.

PMID- 24893727
TI  - [Periprosthetic and interimplant femoral fractures: Biomechanical analysis].
AB  - BACKGROUND: The requirements for treatment of femoral fractures are increasing
      with the rising age of the patients. The aim of this study was to evaluate
      femoral stiffness and the fracture risk after inserting different implants and
      implant combinations. METHODS: A total of 48 cadaveric femors were harvested and
      8 groups were randomized on the basis of the bone mineral density (BMD).
      Different osteosyntheses following prosthetic stem implantation (hip and knee
      prostheses) were performed and compared with native femurs. All specimens were
      biomechanically tested in a four-point bending until fracture. RESULTS: The
      insertion of a femoral stem decreases the stiffness by approximately 33%.
      Ipsilateral retrograde nailing reduces the force to failure even more. This
      instable situation can be stabilized by a lateral locking compression plate. The
      most stable situation occurred in the presence of two cemented stems. CONCLUSION:
      Taken together these results clearly indicate that a hip prosthesis significantly
      weakens the femur, whereas two stems produce the most stable situation at all.
      The situation of a hip prosthesis and an retrograde nail should be avoided or
      covered by a bridging-osteosynthesis. In clinical practice an extramedullary
      fixation technique for distal femoral fractures should be preferred.

PMID- 24893728
TI  - [Current practice in coagulation and transfusion therapy in multiple trauma
      patients: A German nation-wide online survey].
AB  - BACKGROUND: In recent years, the treatment of trauma-associated coagulopathy and
      bleeding has advanced enormously. The aim of this study was to assess the current
      practice of coagulation and transfusion management in Germany. PATIENTS AND
      METHODS: From October 2011 until January 2012 we conducted a survey via online
      questionnaire that was sent per E-Mail to all members of the German Society for
      Trauma Surgery. It comprised 12 questions with respect to current treatment of
      coagulopathy and haemorrhage in trauma patients. RESULTS: The response rate was
      145/3006 (5 %). The respondents had following specialties: 77.2 % trauma surgery
      15.9 % anesthesiology, 6.9 % others. 64 % of respondents were employed by a Level
      1 trauma centre, wheras 17 % worked in a local level 3 centre. The majority (94
      %) claimed to treat hypothermia regularly. Only about half of the participants
      reported to follow a massive transfusion protocol in their institution. The
      potential components of these protocols were reported in varying rates, being it
      well-established components (e.g. FFP 78 %; Fibrinogen 75 %) or therapies with
      poor evidence in multiple trauma (Desmopressin 39 %, rFVIIa 47 %). Calcium was
      provided by only 48 % of respondents although generally recommended in all
      guidelines. CONCLUSION: The current study suggests that in Germany strategies and
      principles regarding management of trauma-associated coagulopathy are
      standardized only poorly. Level 1 centres appear to apply a more advanced
      approach, however to much variability exists with respect to the components of
      the transfusion protocols. The low response rate indicates that most German
      trauma surgeons consider coagulation and hemorrhage as "expert-topics" beyond
      their field of duty.

PMID- 24893729
TI  - The importance of the cleavage stage morphology evaluation for blastocyst
      transfer in patients with good prognosis.
AB  - PURPOSE: To evaluate: (i) the influence of morphology at cleavage stage on
      blastocyst formation and implantation, and (ii) whether the transfer of low
      quality embryos on day-three would be a better approach than the transfer at
      blastocyst stage. METHODS: This study included 8,444 embryos obtained from 1,125
      patients undergoing ICSI cycles between January/2011 and September/2013. The
      influence of the quality of the embryo on days-two and -three on blastocyst
      formation and implantation success was evaluated. Moreover, the implantation
      potential of low-quality embryos, at cleavage stage, transferred on day-three was
      compared with the implantation potential of low-quality embryos, at cleavage
      stage, transferred on day-five. RESULTS: Low-quality embryos on day-two had an
      approximate 20 % decreased chance of achieving the blastocyst stage, and
      blastocysts derived from low-quality embryos on day-two had a nearly 40 %
      decrease in the implantation chance. Low-quality embryos on day-three had a 30 %
      decreased chance of achieving the blastocyst stage, and blastocysts derived from
      low-quality embryos on day-three had an almost 40 % decreased implantation
      chance. The implantation rate didn't differ when low-quality embryos on the
      cleavage stage were transferred on day-three or left in culture and transferred
      on day-five. CONCLUSIONS: The transfer of low-quality embryos on day-three is a
      better approach than transfer at the blastocyst stage. In addition, the embryo
      morphology evaluation at the cleavage stage is still needed for the selection of
      the embryo with the best implantation potential in extended embryo culture
      programmes.

PMID- 24893731
TI  - Awards, lectures, and fellowships sponsored by the AANS/CNS Section on Tumors.
AB  - A major goal of the Section on Tumors of the American Association of Neurological
      Surgery (AANS) and Congress of Neurological Surgeons (CNS) since it was founded
      in 1984 has been to foster both education and research in the field of brain
      tumor treatment and development. In support of this goal, the Section sponsors a
      number of awards, named lectures, and fellowships at the annual meetings of the
      AANS and CNS. In this article, we describe the awards given by the AANS/CNS
      Section on Tumors since its foundation, the recipients of the awards, and their
      philanthropic donors. The subsequent history of awardees and their work is
      briefly examined. Specifically for the Preuss and Mahaley Awards, this article
      also examines the rates of publication among the award-winning abstracts and
      achievement of grant funding by awardees. 

PMID- 24893730
TI  - Episensitization: therapeutic tumor resensitization by epigenetic agents: a
      review and reassessment.
AB  - Resistance to chemotherapy, biological and targeted therapies is an important
      clinical problem. Resistance can arise and/or be selected for multiple mechanisms
      of action. Unfortunately, acquired resistance to antitumor agents or regimens is
      nearly inevitable in all patients with metastatic disease. Until recently, it was
      believed that this resistance was unalterable and irreversible, rendering
      retreatment with the same or similar drugs futile in most cases. However, the
      introduction of epigenetic therapies, including HDAC inhibitors and DNA
      methyltransferase inhibitors (DNMTIs), has provided oncologists with new
      strategies to potentially overcome this resistance. For example, if
      chemoresistance is the product of multiple non-genetic alterations, which develop
      and accumulate over time in response to treatment, then the ability to
      epigenetically modify the tumor to reconfigure it back to its baseline non
      resistant state, holds tremendous promise for the treatment of advanced,
      metastatic cancer. This minireview aims (1) to explore the potential mechanisms
      by which a group of small molecule agents including HDACs (entinostat and
      vorinostat), DNA hypomethylating agents such as the DNMTIs (decitabine (DEC), 5
      azacytidine (5-AZA)) and redox modulators (RRx-001) may reprogram the tumors from
      a refractory to non-refractory state, (2) highlight some recent findings in this
      area, and (3) discuss the therapeutic potential of resensitization approaches
      with formerly failed chemotherapies. 

PMID- 24893732
TI  - Apparent diffusion coefficient in glioblastoma with PNET-like components, a GBM
      variant.
AB  - Glioblastoma (GBM) with primitive neuroectodermal tumor (PNET)-like (GBM-PNET)
      components is a rare variant of GBM. Recent studies describe PNET-like clinical
      behavior in these patients-with significantly increased propensity for CSF
      dissemination and a benefit of "PNET-like" chemotherapy. The imaging appearance
      of GBM-PNET is not well-described and given areas of marked cellularity in the
      PNET components one might expect significantly reduced diffusion on MRI. The
      purpose of this study is to quantitatively evaluate the diffusion characteristics
      in GBM-PNET and compare them with conventional GBMs. Nine patients with surgical
      specimens yielding GBM-PNET were identified from the UCSF Pathology files. MR
      images of these patients were reviewed retrospectively. DWI (diffusion-weighted
      imaging) sequences were analyzed with multiple regions of interests placed within
      the tumor, and ADC (apparent diffusion coefficient) values were measured. Results
      were compared to previously published ADC values in pathology-proven conventional
      GBM cases from our institution. Reduced ADC was seen in GBM-PNET (mean 581 * 10(
      6) mm(2)/s, range 338-817) compared to previously published mean of 1,030 * 10(
      6) mm(2)/s in the enhancing components of conventional GBMs. We report
      substantially reduced ADC values in GBM-PNETs compared to conventional GBMs. If
      demonstrated in a larger sample, when areas of marked reduced diffusion are seen
      in a suspected GBM, MRI may appropriately direct tissue sampling and can advocate
      a thorough search for PNET-like components on histopathology. These patients may
      have a higher chance of developing CSF dissemination and may benefit from "PNET
      like" platinum-based chemotherapy.

PMID- 24893734
TI  - Unseen fearful faces influence face encoding: evidence from ERPs in hemianopic
      patients.
AB  - Visual threat-related signals are not only processed via a cortical geniculo
      striatal pathway to the amygdala but also via a subcortical colliculo-pulvinar
      amygdala pathway, which presumably mediates implicit processing of fearful
      stimuli. Indeed, hemianopic patients with unilateral damage to the geniculo
      striatal pathway have been shown to respond faster to seen happy faces in their
      intact visual field when unseen fearful faces were concurrently presented in
      their blind field [Bertini, C., Cecere, R., & Ladavas, E. I am blind, but I "see"
      fear. Cortex, 49, 985-993, 2013]. This behavioral facilitation in the presence of
      unseen fear might reflect enhanced processing of consciously perceived faces
      because of early activation of the subcortical pathway for implicit fear
      perception, which possibly leads to a modulation of cortical activity. To test
      this hypothesis, we examined ERPs elicited by fearful and happy faces presented
      to the intact visual field of right and left hemianopic patients, whereas
      fearful, happy, or neutral faces were concurrently presented in their blind
      field. Results showed that the amplitude of the N170 elicited by seen happy faces
      was selectively increased when an unseen fearful face was concurrently presented
      in the blind field of right hemianopic patients. These results suggest that when
      the geniculo-striate visual pathway is lesioned, the rapid and implicit
      processing of threat signals can enhance facial encoding. Notably, the N170
      modulation was only observed in left-lesioned patients, favoring the hypothesis
      that implicit subcortical processing of fearful signals can influence face
      encoding only when the right hemisphere is intact. 

PMID- 24893735
TI  - Oscillatory responses to semantic and syntactic violations.
AB  - EEG studies employing time-frequency analysis have revealed changes in theta and
      alpha power in a variety of language and memory tasks. Semantic and syntactic
      violations embedded in sentences evoke well-known ERPs, but little is known about
      the oscillatory responses to these violations. We investigated oscillatory
      responses to both kinds of violations, while monolingual and bilingual
      participants performed an acceptability judgment task. Both violations elicited
      power decreases (event-related desynchronization, ERD) in the 8-30 Hz frequency
      range, but with different scalp topographies. In addition, semantic anomalies
      elicited power increases (event-related synchronization, ERS) in the 1-5 Hz
      frequency band. The 1-5 Hz ERS was strongly phase-locked to stimulus onset and
      highly correlated with time domain averages, whereas the 8-30 Hz ERD response
      varied independently of these. In addition, the results showed that language
      expertise modulated 8-30 Hz ERD for syntactic violations as a function of the
      executive demands of the task. When the executive function demands were increased
      using a grammaticality judgment task, bilinguals but not monolinguals
      demonstrated reduced 8-30 Hz ERD for syntactic violations. These findings suggest
      a putative role of the 8-30 Hz ERD response as a marker of linguistic processing
      that likely represents a separate neural process from those underlying ERPs. 

PMID- 24893736
TI  - Abnormal center-periphery gradient in spatial attention in simultanagnosia.
AB  - Patients suffering from simultanagnosia cannot perceive more than one object at a
      time. The underlying mechanism is incompletely understood. One hypothesis is that
      simultanagnosia reflects "tunnel vision," a constricted attention window around
      gaze, which precludes the grouping of individual objects. Although this idea has
      a long history in neuropsychology, the question whether the patients indeed have
      an abnormal attention gradient around the gaze has so far not been addressed.
      Here we tested this hypothesis in two simultanagnosia patients with bilateral
      parieto-occipital lesions and two control groups, with and without brain damage.
      We assessed the participants' ability to discriminate letters presented briefly
      at fixation with and without a peripheral distractor or in the visual periphery,
      with or without a foveal distractor. A constricted span of attention around gaze
      would predict an increased susceptibility to foveated versus peripheral
      distractors. Contrary to this prediction and unlike both control groups, the
      patients' ability to discriminate the target decreased more in the presence of
      peripheral compared with foveated distractors. Thus, the attentional spotlight in
      simultanagnosia does not fall on foveated objects as previously assumed, but
      rather abnormally highlights the periphery. Furthermore, we found the same center
      periphery gradient in the patients' ability to recognize multiple objects. They
      detected multiple, but not single objects more accurately in the periphery than
      at fixation. These results suggest that an abnormal allocation of attention
      around the gaze can disrupt the grouping of individual objects into an integrated
      visual scene. 

PMID- 24893738
TI  - Morphology of primary visual cortex predicts individual differences in fixation
      duration during text reading.
AB  - In skilled reading, fixations are brief periods of time in which the eyes settle
      on words. E-Z Reader, a computational model of dynamic reading, posits that
      fixation durations are under real-time control of lexical processing. Lexical
      processing, in turn, requires efficient visual encoding. Here we tested the
      hypothesis that individual differences in fixation durations are related to
      individual differences in the efficiency of early visual encoding. To test this
      hypothesis, we recorded participants' eye movements during reading. We then
      examined individual differences in fixation duration distributions as a function
      of individual differences in the morphology of primary visual cortex measured
      from MRI scans. The results showed that greater gray matter surface area and
      volume in visual cortex predicted shorter and less variable fixation durations in
      reading. These results suggest that individual differences in eye movements
      during skilled reading are related to initial visual encoding, consistent with
      models such as E-Z Reader that emphasize lexical control over fixation time. 

PMID- 24893739
TI  - Aerobic fitness predicts relational memory but not item memory performance in
      healthy young adults.
AB  - Health factors such as an active lifestyle and aerobic fitness have long been
      linked to decreased risk of cardiovascular disease, stroke, and other adverse
      health outcomes. Only more recently have researchers begun to investigate the
      relationship between aerobic fitness and memory function. Based on recent
      findings in behavioral and cognitive neuroscience showing that the hippocampus
      might be especially sensitive to the effects of exercise and fitness, the current
      study assessed hippocampal-dependent relational memory and non-hippocampal
      dependent item memory in young adults across a range of aerobic fitness levels.
      Aerobic fitness was assessed using a graded exercise test to measure oxygen
      consumption during maximal exercise (VO2max), and relational and item memory were
      assessed using behavioral and eye movement measures. Behavioral results indicated
      that aerobic fitness was positively correlated with relational memory performance
      but not item memory performance, suggesting that the beneficial effects of
      aerobic fitness selectively affect hippocampal function and not that of the
      surrounding medial temporal lobe cortex. Eye movement results further supported
      the specificity of this fitness effect to hippocampal function, in that aerobic
      fitness predicted disproportionate preferential viewing of previously studied
      relational associations but not of previously viewed items. Potential mechanisms
      underlying this pattern of results, including neurogenesis, are discussed. 

PMID- 24893737
TI  - Age-related differences in the neural bases of phonological and semantic
      processes.
AB  - Changes in language functions during normal aging are greater for phonological
      compared with semantic processes. To investigate the behavioral and neural basis
      for these age-related differences, we used fMRI to examine younger and older
      adults who made semantic and phonological decisions about pictures. The
      behavioral performance of older adults was less accurate and less efficient than
      younger adults' in the phonological task but did not differ in the semantic task.
      In the fMRI analyses, the semantic task activated left-hemisphere language
      regions, and the phonological task activated bilateral cingulate and ventral
      precuneus. Age-related effects were widespread throughout the brain and most
      often expressed as greater activation for older adults. Activation was greater
      for younger compared with older adults in ventral brain regions involved in
      visual and object processing. Although there was not a significant Age *
      Condition interaction in the whole-brain fMRI results, correlations examining the
      relationship between behavior and fMRI activation were stronger for younger
      compared with older adults. Our results suggest that the relationship between
      behavior and neural activation declines with age, and this may underlie some of
      the observed declines in performance. 

PMID- 24893740
TI  - Reward acts on the pFC to enhance distractor resistance of working memory
      representations.
AB  - Working memory and reward processing are often thought to be separate, unrelated
      processes. However, most daily activities involve integrating these two types of
      information, and the two processes rarely, if ever, occur in isolation. Here, we
      show that working memory and reward interact in a task-dependent manner and that
      this task-dependent interaction involves modulation of the pFC by the ventral
      striatum. Specifically, BOLD signal during gains relative to losses in the
      ventral striatum and pFC was associated not only with enhanced distractor
      resistance but also with impairment in the ability to update working memory
      representations. Furthermore, the effect of reward on working memory was
      accompanied by differential coupling between the ventral striatum and ignore
      related regions in the pFC. Together, these data demonstrate that reward-related
      signals modulate the balance between cognitive stability and cognitive
      flexibility by altering functional coupling between the ventral striatum and the
      pFC. 

PMID- 24893741
TI  - Done that: short-term repetition related modulations of motor cortex activity as
      a stable signature for overnight motor memory consolidation.
AB  - An almost universally accepted tacit expectation is that learning and memory
      consolidation processes must be reflected in the average brain activity in brain
      areas relevant to task performance. Motor cortex (M1) plasticity has been
      implicated in motor skill acquisition and its consolidation. Nevertheless, no
      consistent pattern of changes in the average signal, related to motor learning or
      motor memory consolidation following a single session of training, has emerged
      from imaging studies. Here we show that the pattern and magnitude of short-term
      brain activity modulations in response to task repetition, in M1, may provide a
      robust signature for effective motor memory consolidation processes. We studied
      participants during the paced performance of a finger-to-thumb opposition
      sequence (FOS), intensively trained a day earlier, and a similarly constructed
      untrained FOS. In addition to within-session "on-line" gains, most participants
      expressed delayed, consolidation-phase gains in the performance of the trained
      FOS. The execution of the trained FOS induced repetition enhancements in the
      contralateral M1 and bilaterally in the medial-temporal lobes, offsetting novelty
      related repetition suppression effects. Moreover, the M1 modulations were
      positively correlated with the magnitude of each participant's overnight delayed
      gains but not with absolute performance levels. Our results suggest that short
      term enhancements of brain signals upon task repetition reflect the effectiveness
      of overnight motor memory consolidation. We propose that procedural memory
      consolidation processes may affect the excitation-inhibition balance within
      cortical representations of the trained movements; this new balance is better
      reflected in repetition effects than in the average level of evoked neural
      activity. 

PMID- 24893743
TI  - Early anticipation lies behind the speed of response in conversation.
AB  - RTs in conversation, with average gaps of 200 msec and often less, beat standard
      RTs, despite the complexity of response and the lag in speech production (600
      msec or more). This can only be achieved by anticipation of timing and content of
      turns in conversation, about which little is known. Using EEG and an experimental
      task with conversational stimuli, we show that estimation of turn durations are
      based on anticipating the way the turn would be completed. We found a neuronal
      correlate of turn-end anticipation localized in ACC and inferior parietal lobule,
      namely a beta-frequency desynchronization as early as 1250 msec, before the end
      of the turn. We suggest that anticipation of the other's utterance leads to
      accurately timed transitions in everyday conversations. 

PMID- 24893742
TI  - Auditory evoked responses in musicians during passive vowel listening are
      modulated by functional connectivity between bilateral auditory-related brain
      regions.
AB  - Currently, there is striking evidence showing that professional musical training
      can substantially alter the response properties of auditory-related cortical
      fields. Such plastic changes have previously been shown not only to abet the
      processing of musical sounds, but likewise spectral and temporal aspects of
      speech. Therefore, here we used the EEG technique and measured a sample of
      musicians and nonmusicians while the participants were passively exposed to
      artificial vowels in the context of an oddball paradigm. Thereby, we evaluated
      whether increased intracerebral functional connectivity between bilateral
      auditory-related brain regions may promote sensory specialization in musicians,
      as reflected by altered cortical N1 and P2 responses. This assumption builds on
      the reasoning that sensory specialization is dependent, at least in part, on the
      amount of synchronization between the two auditory-related cortices. Results
      clearly revealed that auditory-evoked N1 responses were shaped by musical
      expertise. In addition, in line with our reasoning musicians showed an overall
      increased intracerebral functional connectivity (as indexed by lagged phase
      synchronization) in theta, alpha, and beta bands. Finally, within-group
      correlative analyses indicated a relationship between intracerebral beta band
      connectivity and cortical N1 responses, however only within the musicians' group.
      Taken together, we provide first electrophysiological evidence for a relationship
      between musical expertise, auditory-evoked brain responses, and intracerebral
      functional connectivity among auditory-related brain regions. 

PMID- 24893744
TI  - The neural substrates of drawing: a voxel-based morphometry analysis of
      constructional, hierarchical, and spatial representation deficits.
AB  - Deficits in the ability to draw objects, despite apparently intact perception and
      motor abilities, are defined as constructional apraxia. Constructional deficits,
      often diagnosed based on performance on copying complex figures, have been
      reported in a range of pathologies, perhaps reflecting the contribution of
      several underlying factors to poor figure drawing. The current study provides a
      comprehensive analysis of brain-behavior relationships in drawing disorders based
      on data from a large cohort of subacute stroke patients (n = 358) using whole
      brain voxel-wise statistical analyses linked to behavioral measures from a
      complex figure copy task. We found that (i) overall poor performance on figure
      copying was associated with subcortical lesions (BG and thalamus), (ii)
      lateralized deficits with respect to the midline of the viewer were associated
      with lesions within the posterior parietal lobule, and (iii) spatial positioning
      errors across the entire figure were associated with lesions within visual
      processing areas (lingual gyrus and calcarine) and the insula. Furthermore,
      deficits in reproducing global aspects of form were associated with damage to the
      right middle temporal gyrus, whereas deficits in representing local features were
      linked to the left hemisphere lesions within calcarine cortex (extending into the
      cuneus and precuneus), the insula, and the TPJ. The current study provides strong
      evidence that impairments in separate cognitive mechanisms (e.g., spatial coding,
      attention, motor execution, and planning) linked to different brain lesions
      contribute to poor performance on complex figure copying tasks. The data support
      the argument that drawing depends on several cognitive processes operating via
      discrete neuronal networks and that constructional problems as well as
      hierarchical and spatial representation deficits contribute to poor figure
      copying. 

PMID- 24893745
TI  - Retinotopy versus face selectivity in macaque visual cortex.
AB  - Retinotopic organization is a ubiquitous property of lower-tier visual cortical
      areas in human and nonhuman primates. In macaque visual cortex, the retinotopic
      maps extend to higher-order areas in the ventral visual pathway, including area
      TEO in the inferior temporal (IT) cortex. Distinct regions within IT cortex are
      also selective to specific object categories such as faces. Here we tested the
      topographic relationship between retinotopic maps and face-selective patches in
      macaque visual cortex using high-resolution fMRI and retinotopic face stimuli.
      Distinct subregions within face-selective patches showed either (1) a coarse
      retinotopic map of eccentricity and polar angle, (2) a retinotopic bias to a
      specific location of visual field, or (3) nonretinotopic selectivity. In general,
      regions along the lateral convexity of IT cortex showed more overlap between
      retinotopic maps and face selectivity, compared with regions within the STS.
      Thus, face patches in macaques can be subdivided into smaller patches with
      distinguishable retinotopic properties. 

PMID- 24893746
TI  - Differentiating semantic categories during the acquisition of novel words:
      correspondence analysis applied to event-related potentials.
AB  - Growing evidence suggests that semantic knowledge is represented in distributed
      neural networks that include modality-specific structures. Here, we examined the
      processes underlying the acquisition of words from different semantic categories
      to determine whether the emergence of visual- and action-based categories could
      be tracked back to their acquisition. For this, we applied correspondence
      analysis (CA) to ERPs recorded at various moments during acquisition. CA is a
      multivariate statistical technique typically used to reveal distance
      relationships between words of a corpus. Applied to ERPs, it allows isolating
      factors that best explain variations in the data across time and electrodes.
      Participants were asked to learn new action and visual words by associating novel
      pseudowords with the execution of hand movements or the observation of visual
      images. Words were probed before and after training on two consecutive days. To
      capture processes that unfold during lexical access, CA was applied on the 100
      400 msec post-word onset interval. CA isolated two factors that organized the
      data as a function of test sessions and word categories. Conventional ERP
      analyses further revealed a category-specific increase in the negativity of the
      ERPs to action and visual words at the frontal and occipital electrodes,
      respectively. The distinct neural processes underlying action and visual words
      can thus be tracked back to the acquisition of word-referent relationships and
      may have its origin in association learning. Given current evidence for the
      flexibility of language-induced sensory-motor activity, we argue that these
      associative links may serve functions beyond word understanding, that is, the
      elaboration of situation models. 

PMID- 24893748
TI  - Coronary artery bypass grafting versus drug-eluting stents in patients with
      severe coronary artery disease and diabetes mellitus: systematic review and meta
      analysis.
AB  - BACKGROUND: A comprehensive meta-analysis was performed to evaluate the
      comparative benefits of coronary artery bypass grafting (CABG) versus drug
      eluting stents (DES) in patients with diabetes mellitus and severe coronary
      artery disease (CAD). METHODS: A comprehensive literature search of PubMed,
      Embase, and ScienceDirect was undertaken. References cited with the papers were
      also checked to identify relevant articles. RESULTS: In all, four randomized
      controlled trials, two prospective registries, and 11 retrospective studies were
      identified for review. Pooled analysis demonstrated that DES was associated with
      lower all-cause mortality at Day 30. However, there was no significant difference
      between CABG and DES in mortality at 12 months and at maximum follow-up.
      Furthermore, DES was associated with lower overall and major adverse cardiac and
      cerebrovascular events (MACCE)-free survival, as well as a higher incidence of
      myocardial infarction and repeat revascularization. In contrast, CABG was
      associated with an increased risk of stroke. CONCLUSIONS: For patients with
      diabetes mellitus and severe CAD, CABG is superior to DES in that it
      significantly improves overall and MACCE-free survival and reduces the incidence
      of myocardial infarction and repeat revascularization in the long term, although
      it is associated with greater perioperative risk and a higher incidence of
      stroke. Therefore, CABG should remain the gold standard for these patients.

PMID- 24893749
TI  - Synthesis of benzoxazoles from 2-aminophenols and beta-diketones using a combined
      catalyst of Bronsted acid and copper iodide.
AB  - Cyclization reactions of 2-aminophenols with beta-diketones catalyzed by a
      combination of Bronsted acid and CuI are presented. Various 2-substituted
      benzoxazoles were obtained through these reactions. Different substituents such
      as methyl, chloro, bromo, nitro, and methoxy on 2-aminophenol are tolerated under
      the optimized reaction conditions. 

PMID- 24893747
TI  - A combination of p300 and Braf expression in the diagnosis and prognosis of
      melanoma.
AB  - BACKGROUND: To date only a handful of drugs are available for the treatment of
      melanoma. Among them vemurafenib, a BrafV600E specific inhibitor, showed
      promising results in terms of response rate and increase in median survival time.
      However, its effectiveness is limited by development of resistance and the search
      for additional drugs for melanoma treatment is ongoing. The present study was
      performed to analyze the correlation between Braf expression and the expression
      of p300, a known down stream target of the mitogen activated protein kinase
      (MAPK) pathway, which was recently shown by us to be a prognostic marker for
      melanoma progression and patient survival. METHODS: The expression of Braf and
      p300 expression were correlated and analyzed by Chi-square test. A total of 327
      melanoma patient cases (193 primary melanoma and 134 metastatic melanoma) were
      used for the study. Classification & regression tree (CRT), Kaplan-Meier, and
      multivariate Cox regression analysis were used to elucidate the significance of
      the combination of Braf and p300 expression in the diagnosis and prognosis of
      melanoma. RESULTS: Our results demonstrate that Braf expression is inversely
      correlated with nuclear p300 and positively correlated with cytoplasmic p300
      expression. Braf and cytoplasmic p300 were found to be associated with melanoma
      progression, tumor size and ulceration status. CRT analysis revealed that a
      combination of Braf and p300 expression (nuclear and cytoplasmic), could be used
      to distinguish between nevi and melanoma, and primary from metastatic melanoma
      lesions. The combination of Braf and nuclear p300 was significantly associated
      with patient survival and nuclear p300 was found to be an independent predictor
      of patient survival. CONCLUSION: Our results indicate a cross-talk between Braf
      and p300 in melanoma and demonstrate the importance Braf and p300 expression in
      the diagnosis and prognosis of melanoma.

PMID- 24893750
TI  - The impact of diabetes mellitus and glycemic control on clinical outcomes
      following liver transplant for hepatitis C.
AB  - Hepatitis C is the leading indication for liver transplantation in the USA and
      recurrence is universal. The impact of preexisting diabetes, new-onset diabetes
      after transplant (NODAT), and glycemic control on fibrosis progression has not
      been studied. This retrospective longitudinal cohort study included adult liver
      recipients with hepatitis C transplanted between 2000 and 2011. Patients were
      divided into three groups: preexisting diabetes (n = 41), NODAT (n = 59), and no
      diabetes (n = 103). Patients with preexisting diabetes (70%) or NODAT (59%) were
      more likely to develop hepatitis C recurrence (>=stage 1 fibrosis), as compared
      to non-diabetics (36%, p = 0.006). There was also a trend toward a higher
      incidence of at least Stage 2 fibrosis (36% and 48% vs. 23%, respectively; p =
      0.063). Patients with tight glycemic control had a lower rate of Stage 2 fibrosis
      development (78% vs. 60%, p = 0.027), while those with good control (<150 mg/dL)
      also had lower rates of Stage 2 fibrosis (84% vs. 62%, p = 0.004). Multivariable
      analysis verified a decreased rate of recurrence for patients with blood glucose
      <138 mg/dL (p = 0.021), after controlling for confounders. These results
      demonstrate that diabetes is strongly associated with an increased risk of
      hepatitis C virus-related fibrosis development and glycemic control may reduce
      the risk and severity of recurrence.

PMID- 24893752
TI  - Computational discovery of soybean promoter cis-regulatory elements for the
      construction of soybean cyst nematode-inducible synthetic promoters.
AB  - Computational methods offer great hope but limited accuracy in the prediction of
      functional cis-regulatory elements; improvements are needed to enable synthetic
      promoter design. We applied an ensemble strategy for de novo soybean cyst
      nematode (SCN)-inducible motif discovery among promoters of 18 co-expressed
      soybean genes that were selected from six reported microarray studies involving a
      compatible soybean-SCN interaction. A total of 116 overlapping motif regions
      (OMRs) were discovered bioinformatically that were identified by at least four
      out of seven bioinformatic tools. Using synthetic promoters, the inducibility of
      each OMR or motif itself was evaluated by co-localization of gain of function of
      an orange fluorescent protein reporter and the presence of SCN in transgenic
      soybean hairy roots. Among 16 OMRs detected from two experimentally confirmed SCN
      inducible promoters, 11 OMRs (i.e. 68.75%) were experimentally confirmed to be
      SCN-inducible, leading to the discovery of 23 core motifs of 5- to 7-bp length,
      of which 14 are novel in plants. We found that a combination of the three best
      tools (i.e. SCOPE, W-AlignACE and Weeder) could detect all 23 core motifs. Thus,
      this strategy is a high-throughput approach for de novo motif discovery in
      soybean and offers great potential for novel motif discovery and synthetic
      promoter engineering for any plant and trait in crop biotechnology. 

PMID- 24893753
TI  - Spatial ranking strategy and enhanced peripheral vision discrimination optimize
      performance and efficiency of visual sequential search.
AB  - Visual sequential search might use a peripheral spatial ranking of the scene to
      put the next target of the sequence in the correct order. This strategy, indeed,
      might enhance the discriminative capacity of the human peripheral vision and
      spare neural resources associated with foveation. However, it is not known how
      exactly the peripheral vision sustains sequential search and whether the sparing
      of neural resources has a cost in terms of performance. To elucidate these
      issues, we compared strategy and performance during an alpha-numeric sequential
      task where peripheral vision was modulated in three different conditions: normal,
      blurred, or obscured. If spatial ranking is applied to increase the peripheral
      discrimination, its use as a strategy in visual sequencing should differ
      according to the degree of discriminative information that can be obtained from
      the periphery. Moreover, if this strategy spares neural resources without
      impairing the performance, its use should be associated with better performance.
      We found that spatial ranking was applied when peripheral vision was fully
      available, reducing the number and time of explorative fixations. When the
      periphery was obscured, explorative fixations were numerous and sparse; when the
      periphery was blurred, explorative fixations were longer and often located close
      to the items. Performance was significantly improved by this strategy. Our
      results demonstrated that spatial ranking is an efficient strategy adopted by the
      brain in visual sequencing to highlight peripheral detection and discrimination;
      it reduces the neural cost by avoiding unnecessary foveations, and promotes
      sequential search by facilitating the onset of a new saccade. 

PMID- 24893751
TI  - Effects of ultraviolet radiation (UVA+UVB) on young gametophytes of Gelidium
      floridanum: growth rate, photosynthetic pigments, carotenoids, photosynthetic
      performance, and ultrastructure.
AB  - This study investigated the effects of radiation (PAR+UVA+UVB) on the development
      and growth rates (GRs) of young gametophytes of Gelidium floridanum. In addition,
      photosynthetic pigments were quantified, carotenoids identified, and
      photosynthetic performance assessed. Over a period of 3 days, young gametophytes
      were cultivated under laboratory conditions and exposed to photosynthetically
      active radiation (PAR) at 80 MUmol photons m(-2) s(-1) and PAR+UVA (0.70 W m(
      2))+UVB (0.35 W m(-2)) for 3 h per day. The samples were processed for light and
      electron microscopy to analyze the ultrastructure features, as well as carry out
      metabolic studies of GRs, quantify the content of photosynthetic pigments,
      identify carotenoids and assess photosynthetic performance. PAR+UVA+UVB promoted
      increase in cell wall thickness, accumulation of floridean starch grains in the
      cytoplasm and disruption of chloroplast internal organization. Algae exposed to
      PAR+UVA+UVB also showed a reduction in GR of 97%. Photosynthetic pigments, in
      particular, phycoerythrin and allophycocyanin contents, decreased significantly
      from UV radiation exposure. This result agrees with the decrease in
      photosynthetic performance observed after exposure to ultraviolet radiation, as
      measured by a decrease in the electron transport rate (ETR), where values of
      ETRmax declined approximately 44.71%. It can be concluded that radiation is a
      factor that affects the young gametophytes of G. floridanum at this stage of
      development.

PMID- 24893755
TI  - Generalisability of the inflammatory bowel disease knowledge inventory device to
      assess disease-related knowledge in Australian children.
AB  - AIM: Disease knowledge may affect disease outcome, adherence to therapy and
      quality of life in inflammatory bowel disease (IBD). The IBD knowledge inventory
      device (IBD-KID) was specifically developed and validated for children to measure
      disease-specific knowledge. The relevance of the IBD-KID was now determined in an
      Australian population of children with IBD. METHODS: Twenty children with an
      established diagnosis of IBD for 2 years or greater, and their parents, were
      asked to complete the IBD-KID and the Crohn's and Colitis Knowledge Score
      (CCKNOW). Twenty children recently diagnosed with IBD completed the IBD-KID
      alone, as did three populations of health workers within a paediatric hospital.
      RESULTS: Children with longstanding disease scored 12.1 +/- 4.6 (from 23
      questions) in the IBD-KID and 13.2 +/- 5 (from 30 questions) in the CCKNOW device
      (P < 0.05). Children had fewer 'don't know' answers with the IBD-KID. Areas of
      poor knowledge included aspects of IBD therapies and IBD outcome. Recently
      diagnosed children performed less well than those with longer period of illness
      (P = 0.03). Parents scored more highly in both scores than their children (16.8
      +/- 2.7 and 18.1 +/- 4.2: P = 0.008). Medical staff had higher scores in the IBD
      KID (19.5 +/- 2.1) than did nursing (13.2 +/- 2.7) or clerical (7.3 +/- 4.1)
      staff (P < 0.005). CONCLUSIONS: The IBD-KID provides a reliable and appropriate
      assessment of disease knowledge in Australian children with IBD and can now be
      used in activities targeting disease-related education and as a tool to ascertain
      where knowledge can be improved in children with IBD.

PMID- 24893754
TI  - Bacterial community structure and soil properties of a subarctic tundra soil in
      Council, Alaska.
AB  - The subarctic region is highly responsive and vulnerable to climate change.
      Understanding the structure of subarctic soil microbial communities is essential
      for predicting the response of the subarctic soil environment to climate change.
      To determine the composition of the bacterial community and its relationship with
      soil properties, we investigated the bacterial community structure and properties
      of surface soil from the moist acidic tussock tundra in Council, Alaska. We
      collected 70 soil samples with 25-m intervals between sampling points from 0-10
      cm to 10-20 cm depths. The bacterial community was analyzed by pyrosequencing of
      16S rRNA genes, and the following soil properties were analyzed: soil moisture
      content (MC), pH, total carbon (TC), total nitrogen (TN), and inorganic nitrogen
      (NH4+ and NO3-). The community compositions of the two different depths showed
      that Alphaproteobacteria decreased with soil depth. Among the soil properties
      measured, soil pH was the most significant factor correlating with bacterial
      community in both upper and lower-layer soils. Bacterial community similarity
      based on jackknifed unweighted unifrac distance showed greater similarity across
      horizontal layers than through the vertical depth. This study showed that soil
      depth and pH were the most important soil properties determining bacterial
      community structure of the subarctic tundra soil in Council, Alaska.

PMID- 24893757
TI  - [Autism spectrum disorders].

PMID- 24893756
TI  - Venous thromboembolism and underutilisation of anticoagulant thromboprophylaxis
      in hospitalised patients with inflammatory bowel disease.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a well-recognised extra-intestinal
      manifestation of inflammatory bowel disease (IBD). Despite the widespread support
      for anticoagulant prophylaxis in hospitalised IBD patients, the utilisation and
      efficacy in clinical practice are unknown. AIMS: The aim of this study was to
      assess the prevalence and clinical features of VTE among hospitalised IBD
      patients and ascertain whether appropriate thromboprophylaxis had been
      administered. METHODS: All patients with a discharge diagnosis of Crohn disease
      or ulcerative colitis and VTE were retrospectively identified using International
      Classification of Diseases, tenth revision codes from medical records at our
      institution from July 1998 to December 2009. Medical records were then reviewed
      for clinical history and utilisation of thromboprophylaxis. Statistical analysis
      was performed by Mann-Whitney test and either chi(2) tests or Fisher's exact
      tests. RESULTS: Twenty-nine of 3758 (0.8%) IBD admissions suffered VTE, 13
      preadmission and 16 during admission. Of these 29 admissions (in 25 patients),
      24% required intensive care unit and 10% died. Of the 16 venous thrombotic events
      that occurred during an admission, eight (50%) did not receive anticoagulant
      thromboprophylaxis and eight (50%) occurred despite thromboprophylaxis. Most
      thromboembolism despite prophylaxis occurred post-intestinal resection (n = 5,
      63%). CONCLUSION: Thromboprophylaxis is underutilised in half of IBD patients
      suffering VTE. Prescription of thromboprophylaxis for all hospitalised IBD
      patients, including dual pharmacological and mechanical prophylaxis in
      postoperative patients, may lead to a reduction in this preventable complication
      of IBD.

PMID- 24893758
TI  - Discrimination, arrest history, and major depressive disorder in the U.S. Black
      population.
AB  - Everyday discrimination contributes negatively to depressive symptomatology among
      Blacks in the US and being arrested could add to this depression. Using data from
      the National Survey on American Life, the present study determined the
      association between an arrest history and major depressive disorder (MDD), while
      accounting for discrimination among African Americans, US-born Afro-Caribbeans
      and first-generation Black immigrants. Findings from logistic regression analyses
      adjusted for discrimination suggested an arrest history is associated with 12
      month MDD (Adjusted OR=1.47; 95% CI=1.02-2.10) and lifetime MDD (Adjusted OR=1.56
      CI=1.17-2.09). Accounting for drug and alcohol dependence attenuated the
      association between arrest history and 12-month MDD, but not lifetime MDD. The
      associations between arrest history and both 12-month and lifetime MDD, and
      discrimination and lifetime MDD varied by ethnic/immigrant group. Specifically,
      while the association between arrest history and MDD (both 12-month and lifetime)
      was strongest among US-born Afro-Caribbeans, evidence consistent with the
      immigrant paradox, the association between discrimination and lifetime MDD was
      particularly relevant for first-generation Black immigrants, suggesting
      discrimination may hinder the protection of first-generation status. Mental
      health prevention and treatment programs should target the stress associated with
      being arrested and experiencing discrimination among US Blacks. 

PMID- 24893759
TI  - Adolescent inpatient girls' report of dependent life events predicts prospective
      suicide risk.
AB  - Adolescents with a history of suicidal behavior are especially vulnerable for
      future suicide attempts, particularly following discharge from an inpatient
      psychiatric admission. This study is the first to test whether adolescents'
      tendency to generate stress, or report more dependent events to which they
      contributed, was predictive of prospective suicide events. Ninety adolescent
      psychiatric inpatients who were admitted for recent suicide risk, completed
      diagnostic interviews, assessments of history of suicidal behavior, and a self
      report questionnaire of major life events at baseline. Participants were followed
      over the subsequent 6 months after discharge to assess stability vs. onset of
      suicide events. Cox proportional hazard regressions were used to predict
      adolescents' time to suicide events. Results supported hypothesis, such that only
      recent greater dependent events, not independent or overall events, predicted
      risk for prospective suicide events. This effect was specific to adolescent
      girls. Importantly, dependent events maintained statistical significance as a
      predictor of future suicide events after co-varying for the effects of several
      established risk factors and psychopathology. Results suggest that the tendency
      to generate dependent events may contribute unique additional prediction for
      adolescent girls' prospective suicide risk, and highlight the need for future
      work in this area. 

PMID- 24893761
TI  - Characterization of critically ill adult burn patients admitted to a Brazilian
      intensive care unit.
AB  - INTRODUCTION: To characterize the evolution of clinical and physiological
      variables in severe adult burn patients admitted to a Brazilian burn ICU, we
      hypothesized that characteristics of survivors are different from non-survivors
      after ICU admission. METHODS: A five-year observational study was carried out.
      The clinical characteristics, physiological variables, and outcomes were
      collected during this period. RESULTS: A total of 163 patients required ICU
      support and were analyzed. Median age was 34 [25,47] years. Total burn surface
      area (TBSA) was 29 [18,43]%, and hospital mortality rate was 42%. Lethal burn
      area at which fifty percent of patients died (LA50%) was 36.5%. Median SAPS3 was
      41 [34,54]. Factors associated with hospital mortality were analyzed in three
      steps, the first incorporated ICU admission data, the second incorporated first
      day ICU data, and the third incorporated data from the first week of an ICU stay.
      We found a significant association between hospital mortality and SAPS3
      [OR(95%CI)=1.114(1.062-1.168)], TBSA [OR(95%CI)=1.043(1.010-1.076)], suicide
      attempts [OR(95%CI)=8.126(2.284-28.907)], and cumulative fluid balance per liter
      within the first week [OR(95%CI)=1.090(1.030-1.154)]. Inhalation injury was
      present in 45% of patients, and it was not significantly associated with hospital
      mortality. CONCLUSIONS: In this study of an ICU in a developing country, the
      mortality rate of critically ill burn patients was high and the TBSA was an
      independent risk factor for death. SAPS3 at admission and cumulative fluid
      balance in the first seven days, were also associated with unfavorable outcomes.
      The implementation of judicious fluid management after an acute resuscitation
      phase may help to improve outcomes in this scenario.

PMID- 24893762
TI  - Effectiveness of treatment with viscosupplementation in temporomandibular joints
      with or without effusion.
AB  - The objective of this study was to determine whether the effectiveness of
      viscosupplementation with hyaluronic acid (HA) in patients with temporomandibular
      joint (TMJ) degenerative disorders depends on the presence of intra-articular
      effusion. In this study of case-control design, two groups of 25 patients were
      recruited: patients with a clinical diagnosis of painful chronic TMJ
      osteoarthritis and magnetic resonance imaging (MRI) signs of TMJ degeneration,
      with (effusion group) or without (no effusion group) MRI evidence of TMJ
      effusion. All patients underwent five weekly single-needle arthrocenteses plus
      medium molecular weight HA and 6 months of follow-up. Several clinical outcome
      parameters were assessed. For all variables, analysis of variance (ANOVA) for
      repeated measures was performed to assess the existence of significant within
      group and between-group treatment effects. Over time, both groups showed
      significant improvements in all outcome parameters, which were maintained at the
      6-month follow-up (P<0.05). Between-group comparisons showed that the treatment
      effects did not differ significantly for either the primary outcome variable
      (pain levels: F=0.849, P=0.548) or secondary outcome variables (chewing
      efficiency: F=0.854, P=0.544; functional limitation: F=1.35, P=0.226; mouth
      opening: F=0.658, P=0.707). The null hypothesis that there are no differences in
      treatment effectiveness between patients with and without effusion could not be
      rejected.

PMID- 24893763
TI  - Indications for reconstruction of mucosal defects in oropharyngeal cancer using a
      supraclavicular island flap.
AB  - The use of the supraclavicular island flap (SCIF) for the reconstruction of
      facial and neck skin defects is increasing. The value of this fasciocutaneous
      flap as a reconstructive modality for oropharyngeal defects in cancer patients is
      unclear. In the present study, a SCIF was used for reconstruction of mucosal
      defects following resection of the tumour in a group of four patients with T2
      squamous cell carcinoma of the oropharynx and a clinical N0 neck. Reconstruction
      was performed following transoral tumour resection and selective neck dissection
      at levels I-III in the same session. Intraoperative and postoperative
      complications were analyzed, and functional and aesthetic results for the neck
      and shoulder region were evaluated in follow-up examinations. In addition,
      sensation to the flap was evaluated. No flap failures were observed. Only minor
      surgical complications were evident, which did not cause any relevant functional
      or aesthetic impairments. Sensation to the flap was observed in all cases. The
      SCIF appears to be a good and time-saving alternative to free flaps for
      oropharyngeal reconstruction following oncological resection in selected
      patients. 

PMID- 24893760
TI  - Influence of inhalation injury on energy expenditure in severely burned children.
AB  - OBJECTIVE: Determine the effect of inhalation injury on burn-induced
      hypermetabolism in children. DESIGN: Prospective study comparing hypermetabolism
      (i.e., resting energy expenditure and oxygen consumption) in burned children with
      and without inhalation injury during acute hospitalization. SETTING: Single
      pediatric burn center. PATIENTS: Eighty-six children (1-18 years) with >=40%
      total body surface area burns were stratified to two groups: no inhalation injury
      and inhalation injury. INTERVENTIONS: None. MAIN MEASUREMENTS AND RESULTS:
      Inhalation injury was diagnosed based on bronchoscopic evaluation. At admission,
      PaO2:FiO2 ratios (an index of respiratory distress) were significantly higher in
      patients with no inhalation injury than in patients with inhalation injury. No
      differences were detected in resting energy expenditure or percent of the
      predicted basal metabolic rate between groups. Additionally, oxygen consumption
      did not significantly differ between groups. CONCLUSIONS: Inhalation injury does
      not augment the burn-induced hypermetabolic stress response in children, as
      reflected by resting energy expenditure and oxygen consumption.

PMID- 24893764
TI  - Inferolateral marginal orbitectomy: a simple adjuvant technique for orbital
      decompression.
AB  - The number of patients with mild exophthalmos, without severe eye symptoms, who
      wish to undergo aesthetic orbital decompression, is increasing. Removal of the
      lateral and inferior orbital walls is a common procedure for mild to moderate
      exophthalmos. However, the limited space between the globe and the orbital wall
      is often troublesome for surgeons introducing surgical devices. As a result, the
      decompression tends to be insufficient in the posterior region of the orbit. We
      describe a simple adjuvant surgical technique to address this limitation. Through
      a laterally extended, transconjunctival approach, the inferior and lateral
      margins of the orbit are removed in a crescent shape before the actual
      decompression. This manoeuvre widens the working space and offers better
      visibility, enabling sufficient removal of the orbital walls. The technique
      presented facilitates the approach to the posterior regions of the orbit,
      enabling surgeons to more easily perform orbital decompression.

PMID- 24893765
TI  - Dental implants in patients at high risk for infective endocarditis: a
      preliminary study.
AB  - The safety of dental implant placement in patients at high risk for infective
      endocarditis (IE) has never been shown. The outcome of osseointegrated implants
      in patients with artificial heart valves or with a history of an infected valve
      is not known. In this article we describe our experience of dental implant
      placement in patients at high risk for IE. A retrospective study was conducted on
      patients at high risk for IE who underwent dental implant placement. All the
      patients received prophylactic antibiotic treatment before the surgical
      procedure, in accordance with the relevant American Heart Association guidelines.
      A total 13 patients underwent 16 surgical procedures for the placement of 57
      dental implants over a period of 17 years. Within the follow-up period, no case
      of IE was reported. Two implants failed before exposure in one patient, one
      patient suffered from mitral valve thrombosis 14 days after the dental procedure,
      and another patient suffered a stroke 6 months following treatment. Despite the
      limitation of the small group of patients and the known low incidence of IE,
      dental implants may be regarded as a legitimate procedure for patients at high
      risk for IE.

PMID- 24893767
TI  - A proposal to improve ophthalmic education in medical schools.

PMID- 24893766
TI  - Antipruritic effects of the probiotic strain LKM512 in adults with atopic
      dermatitis.
AB  - BACKGROUND: Evidence suggests that intestinal microbiota play an important role
      in the pathogenesis of atopic dermatitis (AD) through induction of
      immunosuppression and immune tolerance; however, the exact underlying mechanism
      is unclear. Few studies to date have examined the effects of probiotics on adult
      type AD. OBJECTIVE: To examine the effects of the probiotic Bifidobacterium
      animalis subsp lactis LKM512 on adult-type AD and the expression of metabolites
      that are known to be influenced by gut microbiota in fecal samples. METHODS:
      Forty-four patients were randomly assigned to receive LKM512 or a placebo and
      underwent medical examinations. Fecal microbiota were analyzed with real-time
      polymerase chain reaction. Metabolomic analysis was conducted to search for
      antipruritic metabolites produced by intestinal bacteria using feces derived from
      3 patients whose itch scores had improved using capillary electrophoresis with
      time-of-flight mass spectrometry. Antipruritic effects of kynurenic acid were
      observed using AD-induced NC/Nga mice. RESULTS: LKM512 administration alleviated
      itch in AD patients compared with controls and improved the dermatology-specific
      quality-of-life scores when compared with the controls. Administration of LKM512
      also increased the expression of the antipruritic and antinociceptive metabolite
      kynurenic acid (KYNA) in patients whose itch score had improved after LKM512
      treatment. In mouse experiments, scratching behavior counts tended to be
      decreased by KYNA injection when compared with no treatment. CONCLUSION: LKM512
      administration may exert antipruritic effects by increasing KYNA production.
      LKM512 could therefore be a potentially effective therapeutic candidate for the
      reduction of pruritus. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier:
      UMIN000005695.

PMID- 24893769
TI  - Synthesis and purification of iodoaziridines involving quantitative selection of
      the optimal stationary phase for chromatography.
AB  - The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through
      reaction of diiodomethyllithium with N-Ts aldimines is described.
      Diiodomethyllithium is prepared by the deprotonation of diiodomethane with
      LiHMDS, in a THF/diethyl ether mixture, at -78  degrees C in the dark. These
      conditions are essential for the stability of the LiCHI2 reagent generated. The
      subsequent dropwise addition of N-Ts aldimines to the preformed
      diiodomethyllithium solution affords an amino-diiodide intermediate, which is not
      isolated. Rapid warming of the reaction mixture to 0  degrees C promotes
      cyclization to afford iodoaziridines with exclusive cis-diastereoselectivity. The
      addition and cyclization stages of the reaction are mediated in one reaction
      flask by careful temperature control. Due to the sensitivity of the
      iodoaziridines to purification, assessment of suitable methods of purification is
      required. A protocol to assess the stability of sensitive compounds to stationary
      phases for column chromatography is described. This method is suitable to apply
      to new iodoaziridines, or other potentially sensitive novel compounds.
      Consequently this method may find application in range of synthetic projects. The
      procedure involves firstly the assessment of the reaction yield, prior to
      purification, by (1)H NMR spectroscopy with comparison to an internal standard.
      Portions of impure product mixture are then exposed to slurries of various
      stationary phases appropriate for chromatography, in a solvent system suitable as
      the eluent in flash chromatography. After stirring for 30 min to mimic
      chromatography, followed by filtering, the samples are analyzed by (1)H NMR
      spectroscopy. Calculated yields for each stationary phase are then compared to
      that initially obtained from the crude reaction mixture. The results obtained
      provide a quantitative assessment of the stability of the compound to the
      different stationary phases; hence the optimal can be selected. The choice of
      basic alumina, modified to activity IV, as a suitable stationary phase has
      allowed isolation of certain iodoaziridines in excellent yield and purity.

PMID- 24893770
TI  - Easy measurement of diffusion coefficients of EGFP-tagged plasma membrane
      proteins using k-Space Image Correlation Spectroscopy.
AB  - Lateral diffusion and compartmentalization of plasma membrane proteins are
      tightly regulated in cells and thus, studying these processes will reveal new
      insights to plasma membrane protein function and regulation. Recently, k-Space
      Image Correlation Spectroscopy (kICS)(1) was developed to enable routine
      measurements of diffusion coefficients directly from images of fluorescently
      tagged plasma membrane proteins, that avoided systematic biases introduced by
      probe photophysics. Although the theoretical basis for the analysis is complex,
      the method can be implemented by nonexperts using a freely available code to
      measure diffusion coefficients of proteins. kICS calculates a time correlation
      function from a fluorescence microscopy image stack after Fourier transformation
      of each image to reciprocal (k-) space. Subsequently, circular averaging, natural
      logarithm transform and linear fits to the correlation function yields the
      diffusion coefficient. This paper provides a step-by-step guide to the image
      analysis and measurement of diffusion coefficients via kICS. First, a high frame
      rate image sequence of a fluorescently labeled plasma membrane protein is
      acquired using a fluorescence microscope. Then, a region of interest (ROI)
      avoiding intracellular organelles, moving vesicles or protruding membrane regions
      is selected. The ROI stack is imported into a freely available code and several
      defined parameters (see Method section) are set for kICS analysis. The program
      then generates a "slope of slopes" plot from the k-space time correlation
      functions, and the diffusion coefficient is calculated from the slope of the
      plot. Below is a step-by-step kICS procedure to measure the diffusion coefficient
      of a membrane protein using the renal water channel aquaporin-3 tagged with EGFP
      as a canonical example. 

PMID- 24893771
TI  - Investigating protein-protein interactions in live cells using bioluminescence
      resonance energy transfer.
AB  - Assays based on Bioluminescence Resonance Energy Transfer (BRET) provide a
      sensitive and reliable means to monitor protein-protein interactions in live
      cells. BRET is the non-radiative transfer of energy from a 'donor' luciferase
      enzyme to an 'acceptor' fluorescent protein. In the most common configuration of
      this assay, the donor is Renilla reniformis luciferase and the acceptor is Yellow
      Fluorescent Protein (YFP). Because the efficiency of energy transfer is strongly
      distance-dependent, observation of the BRET phenomenon requires that the donor
      and acceptor be in close proximity. To test for an interaction between two
      proteins of interest in cultured mammalian cells, one protein is expressed as a
      fusion with luciferase and the second as a fusion with YFP. An interaction
      between the two proteins of interest may bring the donor and acceptor
      sufficiently close for energy transfer to occur. Compared to other techniques for
      investigating protein-protein interactions, the BRET assay is sensitive, requires
      little hands-on time and few reagents, and is able to detect interactions which
      are weak, transient, or dependent on the biochemical environment found within a
      live cell. It is therefore an ideal approach for confirming putative interactions
      suggested by yeast two-hybrid or mass spectrometry proteomics studies, and in
      addition it is well-suited for mapping interacting regions, assessing the effect
      of post-translational modifications on protein-protein interactions, and
      evaluating the impact of mutations identified in patient DNA.

PMID- 24893772
TI  - Interfacial free energy controlling glass-forming ability of Cu-Zr alloys.
AB  - Glass is a freezing phase of a deeply supercooled liquid. Despite its simple
      definition, the origin of glass forming ability (GFA) is still ambiguous, even
      for binary Cu-Zr alloys. Here, we directly study the stability of the supercooled
      Cu-Zr liquids where we find that Cu64Zr36 at a supercooled temperature shows
      deeper undercoolability and longer persistence than other neighbouring
      compositions with an equivalent driving Gibbs free energy. This observation
      implies that the GFA of the Cu-Zr alloys is significantly affected by crystal
      liquid interfacial free energy. In particular, the crystal-liquid interfacial
      free energy of Cu64Zr36 in our measurement was higher than that of other
      neighbouring liquids and, coincidently a molecular dynamics simulation reveals a
      larger glass-glass interfacial energy value at this composition, which reflects
      more distinct configuration difference between liquid and crystal phase. The
      present results demonstrate that the higher crystal-liquid interfacial free
      energy is a prerequisite of good GFA of the Cu-Zr alloys. 

PMID- 24893773
TI  - Ultrafast acousto-plasmonic control and sensing in complex nanostructures.
AB  - Coherent acoustic phonons modulate optical, electronic and mechanical properties
      at ultrahigh frequencies and can be exploited for applications such as ultratrace
      chemical detection, ultrafast lasers and transducers. Owing to their large
      absorption cross-sections and high sensitivities, nanoplasmonic resonators are
      used to generate coherent phonons up to terahertz frequencies. Generating,
      detecting and controlling such ultrahigh frequency phonons has been a topic of
      intense research. Here we report that by designing plasmonic nanostructures
      exhibiting multimodal phonon interference, we can detect the spatial properties
      of complex phonon modes below the optical wavelength through the interplay
      between plasmons and phonons. This allows detection of complex nanomechanical
      dynamics by polarization-resolved transient absorption spectroscopy. Moreover, we
      demonstrate that the multiple vibrational states in nanostructures can be
      tailored by manipulating the geometry and dynamically selected by acousto
      plasmonic coherent control. This allows enhancement, detection and coherent
      generation of tunable strains using surface plasmons. 

PMID- 24893774
TI  - SUMO E3 ligase AtMMS21 is required for normal meiosis and gametophyte development
      in Arabidopsis.
AB  - BACKGROUND: MMS21 is a SUMO E3 ligase that is conserved in eukaryotes, and has
      previously been shown to be required for DNA repair and maintenance of chromosome
      integrity. Loss of the Arabidopsis MMS21 causes defective meristems and dwarf
      phenotypes. RESULTS: Here, we show a role for AtMMS21 during gametophyte
      development. AtMMS21 deficient plants are semisterile with shorter mature
      siliques and abortive seeds. The mms21-1 mutant shows reduced pollen number, and
      viability, and germination and abnormal pollen tube growth. Embryo sac
      development is also compromised in the mutant. During meiosis, chromosome mis
      segregation and fragmentation is observed, and the products of meiosis are
      frequently dyads or irregular tetrads. Several transcripts for meiotic genes
      related to chromosome maintenance and behavior are altered. Moreover,
      accumulation of SUMO-protein conjugates in the mms21-1 pollen grains is distinct
      from that in wild-type. CONCLUSIONS: Thus, these results suggest that AtMMS21
      mediated SUMOylation may stabilize the expression and accumulation of meiotic
      proteins and affect gametophyte development.

PMID- 24893776
TI  - Intra-articular injection of mesenchymal stem cells leads to reduced inflammation
      and cartilage damage in murine antigen-induced arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a debilitating and painful disease
      leading to increased morbidity and mortality and novel therapeutic approaches are
      needed. The purpose of this study was to elucidate if mesenchymal stem cells
      (MSCs) injected in the joints of mice with arthritis are therapeutic, reducing
      joint swelling and cartilage destruction. METHODS: Murine mesenchymal stem cells
      (mMSCs) were isolated from bone marrow of C57Bl/6 mice and expanded in culture.
      Cells were tested for immunophenotype and their ability to form colonies and to
      differentiate into chondrocytes, osteocytes and adipocytes. Antigen-induced
      arthritis (AIA) was induced by intra-articular injection of methylated bovine
      serum albumin into the knee joints of preimmunized C57Bl/6 mice. After one day,
      when peak swelling occurs, 500,000 mMSCs labelled with red fluorescent cell
      tracker CM-DiI were injected intra-articularly in the right knee joint. Left knee
      joints were treated as controls by receiving PBS injections. Differences between
      groups were calculated by Mann Whitney U test or unpaired t tests using GraphPad
      Prism software version 5. RESULTS: Knee joint diameter (swelling) was measured as
      a clinical indication of joint inflammation and this parameter was significantly
      less in MSC-treated mice compared to control-treated animals 48 hours after
      arthritis induction. This difference continued for ~7 days. CM-DiI-labelled MSCs
      were clearly visualised in the lining and sublining layers of synovium, in the
      region of the patella and femoral and tibial surfaces. By day 3, parameters
      indicative of disease severity, including cartilage depletion, inflammatory
      exudate and arthritic index were shown to be significantly reduced in MSC-treated
      animals. This difference continued for 7 days and was further confirmed by
      histological analysis. The serum concentration of tumour necrosis factor alpha
      was significantly decreased following MSC administration. CONCLUSIONS: Our
      results reveal that MSCs injected in the joints of mice with AIA are therapeutic,
      reducing inflammation, joint swelling and cartilage destruction. These cells also
      integrate into the synovium in AIA.

PMID- 24893775
TI  - Validation of the prognostic Heidelberg re-irradiation score in an independent
      mono-institutional patient cohort.
AB  - PURPOSE: Re-irradiation has been shown to be a valid option with proven efficacy
      for recurrent high-grade glioma patients. Overall, up to now it is unclear which
      patients might be optimal candidates for a second course of irradiation. A
      recently reported prognostic score developed by Combs et al. may guide treatment
      decisions and thus, our mono-institutional cohort served as validation set to
      test its relevance for clinical practice. PATIENTS AND METHODS: The prognostic
      score is built upon histology, age (< 50 vs. >= 50 years) and the time between
      initial radiotherapy and re-irradiation (<= 12 vs. > 12 months). This score was
      initially introduced to distinguish patients with excellent (0 points), good (1
      point), moderate (2 points) and poor (3-4 points) post-recurrence survival (PRS)
      after re-irradiation. Median prescribed radiation dose during re-treatment of
      recurrent malignant glioma was 36 Gy in 2 Gy single fractions. A substantial part
      of the patients was additionally treated with bevacizumab (10 mg/kg intravenously
      at d1 and d15 during re-irradiation). RESULTS: 88 patients (initially 61 WHO IV,
      20 WHO III, 7 WHO II) re-irradiated in a single institution were retrospectively
      analyzed. Median follow-up was 30 months and median PRS of the entire patient
      cohort 7 months. Seventy-one patients (80.7%) received bevacizumab. PRS was
      significantly increased in patients receiving bevacizumab (8 vs. 6 months, p =
      0.027, log-rank test). KPS, age, MGMT methylation status, sex, WHO grade and the
      Heidelberg score showed no statistically significant influence on neither PR-PFS
      nor PRS. CONCLUSION: In our cohort which was mainly treated with bevacizumab the
      usefulness of the Heidelberg score could not be confirmed probably due to
      treatment heterogeneity; it can be speculated that larger multicentric data
      collections are needed to derive a more reliable score.

PMID- 24893778
TI  - Risk Factors for Shoulder and Elbow Injuries in High School Baseball Pitchers:
      The Role of Preseason Strength and Range of Motion.
AB  - BACKGROUND: Shoulder strength and motion deficits in high school baseball
      pitchers have been implicated in injury risk. PURPOSE/HYPOTHESIS: To
      prospectively determine if preseason strength and range of motion (ROM) are
      predictive of injury in high school baseball pitchers. It was hypothesized that
      ROM asymmetries and weakness would be predictive of injury. STUDY DESIGN: Case
      control study; Level of evidence, 3. METHODS: Preseason strength and ROM
      measurements were made on 101 pitchers from 4 different high schools over 4
      seasons (total 166 pitcher-seasons: 25 freshman, 46 junior varsity, and 95
      varsity player-seasons). Glenohumeral internal rotation (IR), glenohumeral
      external rotation, and posterior shoulder ROM were measured bilaterally. Strength
      in IR, external rotation, supraspinatus (empty-can test), and scapular retraction
      was measured bilaterally (handheld dynamometer). Injury incidence (injuries per
      1000 pitches) was computed for players categorized as above normal (>=1 SD above
      the mean), normal (within 1 standard deviation of the mean), and below normal
      (<=1 SD below the mean) for each potential risk factor. Injury was defined as a
      missed game or practice because of shoulder or elbow problem. RESULTS: There were
      28 upper extremity injuries (19 shoulder, 9 elbow; incidence, 0.58 injuries/1000
      pitches). There was a trend for supraspinatus weakness to be associated with
      increased injury risk (relative risk [RR], 3.60; 95% CI, 0.75-17.32; P = .09).
      When analyzing major injuries only (>3 missed games), preseason supraspinatus
      weakness was significantly associated with increased injury risk (RR, 4.58; 95%
      CI, 1.40-15.01; P = .02). Paradoxically, pitchers with no IR loss were at
      increased risk compared with pitchers with >=20 degrees  loss (RR, 4.85; 95% CI,
      1.01-23.29; P = .04). Other ROM and strength measures were unrelated to injury
      risk. CONCLUSION: Although excessive loss of IR ROM is thought to be a risk
      factor for injury, the opposite was the case in this study. The absence of IR ROM
      loss in high school pitchers may indicate inadequate prior exposure to pitching,
      resulting in increased injury risk. Preseason supraspinatus weakness was
      associated with increased risk for a major injury, and preventative supraspinatus
      strengthening may be beneficial.

PMID- 24893780
TI  - Towards understanding the behavior of indigo thin films in organic field-effect
      transistors: a template effect of the aliphatic hydrocarbon dielectric on the
      crystal structure and electrical performance of the semiconductor.
AB  - Here we report a systematic investigation of indigo thin films grown on different
      dielectric underlayers. It has been revealed that aliphatic hydrocarbon chains
      serve as templates inducing the formation of a new crystal modification of indigo
      which possesses advanced charge transport properties and affords a dramatic
      improvement in the electrical performance of organic field-effect transistors. 

PMID- 24893777
TI  - Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in
      malaria vaccine studies.
AB  - BACKGROUND: When rhesus monkeys (Macaca mulatta) are used to test malaria
      vaccines, animals are often challenged by the intravenous injection of
      sporozoites. However, natural exposure to malaria comes via mosquito bite, and
      antibodies can neutralize sporozoites as they traverse the skin. Thus,
      intravenous injection may not fairly assess humoral immunity from anti-sporozoite
      malaria vaccines. To better assess malaria vaccines in rhesus, a method to
      challenge large numbers of monkeys by mosquito bite was developed. METHODS:
      Several species and strains of mosquitoes were tested for their ability to
      produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on
      oocyst and sporozoite numbers and mosquito mortality were documented.
      Methylparaben added to mosquito feed was tested to improve mosquito survival. To
      determine the number of bites needed to infect a monkey, animals were exposed to
      various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected
      mosquitoes were used to challenge 17 monkeys in a malaria vaccine trial, and the
      effect of number of infectious bites on monkey parasitaemia was documented.
      RESULTS: Anopheles dirus, Anopheles crascens, and Anopheles dirus X (a cross
      between the two species) produced large numbers of P. knowlesi sporozoites.
      Mosquito survival to day 14, when sporozoites fill the salivary glands, averaged
      only 32% when donor monkeys had a parasitaemia above 2%. However, when donor
      monkey parasitaemia was below 2%, mosquitoes survived twice as well and contained
      ample sporozoites in their salivary glands. Adding methylparaben to sugar
      solutions did not improve survival of infected mosquitoes. Plasmodium knowlesi
      was very infectious, with all monkeys developing blood stage infections if one or
      more infected mosquitoes successfully fed. There was also a dose-response, with
      monkeys that received higher numbers of infected mosquito bites developing
      malaria sooner. CONCLUSIONS: Anopheles dirus, An. crascens and a cross between
      these two species all were excellent vectors for P. knowlesi. High donor monkey
      parasitaemia was associated with poor mosquito survival. A single infected
      mosquito bite is likely sufficient to infect a monkey with P. knowlesi. It is
      possible to efficiently challenge large groups of monkeys by mosquito bite, which
      will be useful for P. knowlesi vaccine studies.

PMID- 24893781
TI  - The evolution of dental materials for hybrid prosthesis.
AB  - Since the immemorial, the replacement of missing teeth has been a medical and
      cosmetic necessity for human kind. Nowadays, middle-aged population groups have
      experienced improved oral health, as compared to previous generations, and the
      percentage of edentulous adults can be expected to further decline. However, with
      the continued increase in the number of older adult population, it is anticipated
      that the need for some form of full-mouth restoration might increase from 53.8
      million in 1991 to 61 million in 2020 [1]. Denture prosthetics has undergone many
      development stages since the first dentures were fabricated. The introduction of
      computer-aided design/computer aided manufacturing (CAD/CAM) has resulted in a
      more accurate manufacturing of prosthetic frameworks, greater accuracy of dental
      restorations, and in particular, implant supported prosthesis. 

PMID- 24893783
TI  - Expert consensus: a flawed process for producing guidelines for the management of
      fluid therapy in the critically ill.

PMID- 24893782
TI  - Epstein-Barr virus, the germinal centre and the development of Hodgkin's
      lymphoma.
AB  - The relationship between Epstein-Barr virus (EBV) and the germinal centre (GC) of
      the asymptomatic host remains an enigma. The occasional appearance of EBV
      positive germinal centres in some patients, particularly those with a history of
      immunosuppression, suggests that EBV numbers in the GC are subject to immune
      control. The relationship, if any, between lymphoid hyperplasia with EBV-positive
      germinal centres and subsequent or concurrent lymphomagenesis remains to be
      clarified. As far as the development of EBV-associated Hodgkin's lymphoma is
      concerned, the suppression of virus replication, mediated by LMP1 on the one
      hand, and the loss of B-cell receptor signalling on the other, appears to be an
      important pathogenic mechanism. A further important emerging concept is that
      alterations in the microenvironment of the EBV-infected B-cell may be important
      for lymphomagenesis. 

PMID- 24893784
TI  - Ultrasound assessment of gastric content and volume.
AB  - Pulmonary aspiration of gastric content is a serious anaesthetic complication
      that can lead to significant morbidity and mortality. Aspiration risk assessment
      is usually based on fasting times. However, fasting guidelines do not apply to
      urgent or emergent situations and to patients with certain co-morbidities.
      Gastric content and volume assessment is a new point-of-care ultrasound
      application that can help determine aspiration risk. This systematic review
      summarizes the current literature on bedside ultrasound assessment of gastric
      content and volume relevant to anaesthesia practice. Seventeen articles were
      identified using predetermined criteria. Studies were classified into those
      describing the sonographic characteristics of different types of gastric content
      (empty, clear fluid, solid), and those describing methods for quantitative
      assessment of gastric volume. A possible algorithm for the clinical application
      of this new tool is proposed, and areas that require further research are
      highlighted. 

PMID- 24893786
TI  - Linking luminance and lightness by global contrast normalization.
AB  - In the present experiment we addressed the question of how the visual system
      determines surface lightness from luminances in the retinal image. We measured
      the perceived lightness of target surfaces that were embedded in custom-made
      checkerboards. The checkerboards consisted of 10 by 10 checks of 10 different
      reflectance values that were arranged randomly across the board. They were
      rendered under six viewing conditions including plain view, with a shadow-casting
      cylinder, or with one of four different transparent media covering part of the
      board. For each reflectance we measured its corresponding luminance in the
      different viewing conditions. We then assessed the lightness matches of four
      observers for each of the reflectances in the different viewing conditions. We
      derived predictions of perceived lightness based on local luminance, Michelson
      contrast, edge integration, anchoring theory, and a normalized Michelson contrast
      measure. The normalized contrast measure was the best predictor of surface
      lightness and was almost as good as the actual reflectance values. The normalized
      contrast measure combines a local computation of Michelson contrast with a region
      based normalization of contrast ranges with respect to the contrast range in
      plain view. How the segregation of image regions is accomplished remains to be
      elucidated.

PMID- 24893785
TI  - Contour inflections are adaptable features.
AB  - An object's shape is a strong cue for visual recognition. Most models of shape
      coding emphasize the role of oriented lines and curves for coding an object's
      shape. Yet inflection points, which occur at the junction of two oppositely
      signed curves, are ubiquitous features in natural scenes and carry important
      information about the shape of an object. Using a visual aftereffect in which the
      perceived shape of a contour is changed following prolonged viewing of a slightly
      different-shaped contour, we demonstrate a specific aftereffect for a contour
      inflection. Control conditions show that this aftereffect cannot be explained by
      adaptation to either the component curves or to the local orientation at the
      point of inflection. Further, we show that the aftereffect transfers weakly to a
      compound curve without an inflection, ruling out a general compound curvature
      detector as an explanation of our findings. We assume however that there are
      adaptable mechanisms for coding other specific forms of compound curves. Taken
      together, our findings provide evidence that the human visual system contains
      specific mechanisms for coding contour inflections, further highlighting their
      role in shape and object coding.

PMID- 24893789
TI  - Diuretic 18F-FDG PET/CT for therapy monitoring in urothelial bladder cancer.

PMID- 24893788
TI  - A role for transcription factor glial cell missing 2 in Ca2+ homeostasis in
      zebrafish, Danio rerio.
AB  - The present study investigated the role of the transcription factor, glial cell
      missing 2 (gcm2), in Ca(2+) regulation in zebrafish larvae. Translational gene
      knockdown of gcm2 decreased Ca(2+) uptake and the density of ionocytes expressing
      the epithelial Ca(2+) channel (ecac), and disrupted the overall Ca(2+) balance.
      Ca(2+) uptake and the expression of gcm2 messenger RNA (mRNA) were significantly
      elevated in larvae acclimated to low Ca(2+) water (25 MUM); the stimulation of
      Ca(2+) uptake was not observed in fish experiencing gcm2 knockdown. Acclimation
      to acidic water (pH 4) significantly reduced whole-body Ca(2+) content owing to
      reduced Ca(2+) uptake and increased Ca(2+) efflux. However, ecac mRNA levels and
      the density of ecac-expressing ionocytes were increased in fish acclimated to
      acidic water, and maximal Ca(2+) uptake capacity (J MAX) was significantly
      increased when measured in control water (pH ~7.4). Acclimation of larvae to
      acidic water significantly increased gcm2 mRNA expression, and in gcm2 morphants,
      no such stimulation in Ca(2+) uptake was observed after their return to control
      water. Overexpression of gcm2 mRNA resulted in a significant increase in the
      numbers of ecac-expressing ionocytes and Ca(2+) uptake. These observations reveal
      a critical role for gcm2 in Ca(2+) homeostasis in zebrafish larvae.

PMID- 24893787
TI  - Short-term respiratory outcomes in late preterm infants.
AB  - OBJECTIVE: To evaluate short-term respiratory outcomes in late preterm infants
      (LPI) compared with those of term infants (TI). METHODS: A retrospective study
      conducted in a single third level Italian centre (2005-2009) to analyse the
      incidence and risk factors of composite respiratory morbidity (CRM), the need for
      adjunctive therapies (surfactant therapy, inhaled nitric oxide, pleural
      drainage), the highest level of respiratory support (mechanical ventilation - MV,
      nasal continuous positive airway pressure--N-CPAP, nasal oxygen) and the duration
      of pressure support (hours in N-CPAP and/or MV). RESULTS: During the study period
      14,515 infants were delivered. There were 856 (5.9%) LPI and 12,948 (89.2%) TI.
      CRM affected 105 LPI (12.4%), and 121 TI (0.9%), with an overall rate of 1.6%.
      Eighty-four LPI (9.8%) and 73 TI (0.56%) received respiratory support, of which
      13 LPI (1.5%) and 16 TI (0.12%) were ventilated. The adjusted OR for developing
      CRM significantly increased from 3.3 (95% CI 2.0-5.5) at 37 weeks to 40.8 (95% CI
      19.7-84.9%) at 34 weeks. The adjusted OR for the need of MV significantly
      increased from 3.4 (95% CI 1.2-10) at 37 weeks to 34.4 (95% CI 6.7-180.6%) at 34
      weeks. Median duration of pressure support was significantly higher at 37 weeks
      (66.6 h vs 40.5 h). Twin pregnancies were related to a higher risk of CRM (OR
      4.3, 95% CI 2.6-7.3), but not independent of gestational age (GA). Cesarean
      section (CS) was associated with higher risk of CRM independently of GA, but the
      OR was lower in CS with labour (2.2, 95% CI 1.4-3.4 vs 3.0, 95% CI 2.1-4.2).
      CONCLUSIONS: In this single third level care study late preterm births, pulmonary
      diseases and supportive respiratory interventions were lower than previously
      documented. LPI are at a higher risk of developing pulmonary disease than TI.
      Infants born from elective cesarean sections, late preterm twins in particular
      and 37 weekers too might benefit from preventive intervention.

PMID- 24893790
TI  - Mycotic aneurysm of the superior mesenteric artery and other sequelae of
      prosthetic valve endocarditis on 18F-FDG PET/CT.

PMID- 24893791
TI  - New EANM paediatric dosage card: optimization of F-18 FDG-administered
      activities.

PMID- 24893792
TI  - Pediatric Radiopharmaceutical Administration: harmonization of the 2007 EANM
      Paediatric Dosage Card (Version 1.5.2008) and the 2010 North American Consensus
      guideline.

PMID- 24893794
TI  - In vivo recording of Zhang's phenomenon (His electrogram alternans): a novel
      index of atrioventricular node dual pathway conduction.
AB  - BACKGROUND: Zhang's phenomenon (originally His electrogram alternans) is a new
      index of atrioventricular node dual pathway electrophysiology. This index has
      been described and validated in isolated hearts in vitro, but has not been
      recorded in vivo. METHODS: This study explored the feasibility of in vivo
      recording of Zhang's phenomenon (His electrogram alternans) in six dogs with a
      custom-built bipolar electrode. RESULTS: The His electrogram recorded from
      superior His bundle domain (superior His electrogram) was high in amplitude at
      basic beats and long coupling intervals (i.e., fast pathway conduction) and low
      amplitude at short prematurities (i.e., slow pathway conduction). In contrast,
      His electrogram recorded from the inferior His bundle domain (inferior His
      electrogram) was always from low amplitude during fast pathway conduction to high
      amplitude during slow pathway conduction. The characteristic His electrogram
      alternans had been recorded in vivo in all six animals. CONCLUSIONS: This study
      provided the first data representing in vivo recording of Zhang's phenomenon (His
      electrogram alternans) in large animals. Clinical studies are needed before this
      novel index can be applied in patients.

PMID- 24893795
TI  - Remote magnetic navigation for circumferential pulmonary vein ablation: single
      catheter technique or additional use of a circular mapping catheter?
AB  - PURPOSE: Remote magnetic navigation (RMN) is utilized for catheter guidance
      during pulmonary vein ablation (PVA). We aimed to determine whether the
      additional use of a circular mapping catheter (CMC) influences efficacy and
      outcome of RMN-guided PVA. METHODS: A total of 80 consecutive subjects (65 %
      male, age 62 +/- 9 years) underwent circumferential PVA with a 3D mapping system
      and an RMN-guided irrigated catheter. Procedural endpoint was complete PV
      isolation (PVI), total radiofrequency (RF) time >60 min, or procedure duration >5
      h. PVI was defined as an entrance and/or exit block, diagnosed with a CMC within
      the PV ostium or by pacing via the roving RMN-guided catheter (single-catheter
      technique). Prolonged Holter monitoring after 3 and 6 months was used to detect
      atrial tachyarrhythmia (AT/AF) recurrences. RESULTS: Complete PVI was achieved in
      56 % (45/80) of all subjects (isolated PVs per patient, 3.1 +/- 1.2; RF time,
      56.3 +/- 17.2 min; procedure duration, 3.8 +/- 0.8 h). Prospective validation of
      the single-catheter technique for diagnosing PVI demonstrated high concordance
      (94 %) with blinded CMC results. CMC use in first-time PVA was associated with
      similar total RF and procedure times but higher PV isolation rate. Upon
      multivariate analysis, CMC use, female gender, left PV, smaller PV ostium and
      repeat PVA predicted PVI during RMN-guided ablation. Persistent AF and mitral
      regurgitation at baseline and the number of non-isolated PVs predicted AT/AF
      recurrence during follow-up. CONCLUSIONS: Concomitant CMC use for first-time, RMN
      guided PVA is associated with similar procedure duration but higher PV isolation
      rates as compared to a single-catheter approach. Since the number of isolated PVs
      predicts freedom from AT/AF, CMC utilization appears advisable for first-time,
      RMN-guided PVA.

PMID- 24893796
TI  - Transcriptome profiling of wheat differentially expressed genes exposed to
      different chemotypes of Fusarium graminearum.
AB  - KEY MESSAGE: The study is an overview of the behavior of the wheat transcriptome
      to the Fusarium graminearum fungus using two different chemotypes. The
      transcriptome profiles of seven putative differentially expressed defense-related
      genes were identified by SSH and further examined using qPCR. Fusarium head
      blight (FHB) of wheat (Triticum aestivum L.), caused by several species of the
      fungus fusarium, is important in all wheat growing regions worldwide. The most
      dominant species in Canada is Fusarium graminearum (Fg). F. graminearum isolates
      producing mycotoxins such as 3-acetyl-deoxynivalenol (3ADON) and 15-acetyl
      deoxynivalenol (15ADON). The objective of this study was to investigate the
      effect of the different chemotypes of Fg on the transcriptome pattern of
      expressed wheat genes. A cDNA library was constructed from infected "Sumai 3"
      spikes harvested at different times after inoculation with a macroconidia
      suspension. Employing suppression subtractive hybridization (SSH), the subtracted
      cDNA library was differentially screened by dot-blot hybridization. Thirty-one
      clones were identified; one was isolated and characterized, and transcriptome
      profiling of seven up-regulated putative defense-related genes was performed
      using quantitative real-time reverse-transcriptase PCR. These genes may be
      involved in the wheat-pathogen interactions revealing transcript accumulation
      differences between the non-diseased, 3ADON-, and 15ADON-infected plants.
      Additionally, significant differences in gene expression were observed between
      3ADON- and 15ADON-infected plants which highlight the significance of a
      particular chemotype in FHB disease.

PMID- 24893797
TI  - Involvement of neurotransmitters in the action of the nociceptin/orphanin FQ
      peptide-receptor system on passive avoidance learning in rats.
AB  - The nociceptin/orphanin FQ peptide (NOP) receptor and its endogenous ligand plays
      role in several physiologic functions of the central nervous system, including
      pain, locomotion, anxiety and depression, reward and drug addiction, learning and
      memory. Previous studies demonstrated that the NOP-receptor system induces
      impairment in memory and learning. However, we have little evidence about the
      underlying neuromodulation. The aim of the present study was to investigate the
      involvement of distinct neurotransmitters in the action of the selective NOP
      receptor agonist orphan G protein-coupled receptor (GPCR) SP9155 P550 on memory
      consolidation in a passive avoidance learning test in rats. Accordingly, rats
      were pretreated with a nonselective muscarinic acetylcholine receptor antagonist,
      atropine, a gamma-aminobutyric acid subunit A (GABA-A) receptor antagonist,
      bicuculline, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a
      nonselective opioid receptor antagonist, naloxone, a non-specific nitric oxide
      synthase inhibitor, nitro-L-arginine, a nonselective alpha-adrenergic receptor
      antagonist, phenoxybenzamine and a beta-adrenergic receptor antagonist,
      propranolol. Atropine, bicuculline, naloxone and phenoxybenzamine reversed the
      orphan GPCR SP9155 P550-induced memory impairment, whereas propranolol,
      haloperidol and nitro-L-arginine were ineffective. Our results suggest that the
      NOP system-induced impairment of memory consolidation is mediated through
      muscarinic cholinergic, GABA-A-ergic, opioid and alpha-adrenergic receptors,
      whereas beta-adrenergic, D2, D3, D4-dopaminergic and nitrergic mechanisms are not
      be implicated. 

PMID- 24893799
TI  - The effects of cardiovascular disease on the clinical outcome of elderly patients
      with diffuse large B-cell lymphoma.
AB  - We identified 3910 elderly (>65 yrs) patients with diffuse large B-cell lymphoma
      (DLBCL) who received doxorubicin-based (+/-rituximab) therapy and 77 347 cancer
      free controls, and assessed cardiovascular events and survival in relation to
      preexisting cardiovascular comorbidities. Compared to controls, patients with
      DLBCL had a 3.4-fold (95%CI 3.0-3.9) and 2.5-fold (95%CI 2.3-2.7) increased risk
      of congestive heart failure (CHF)/cardiomyopathy (CM) within 6 months and 3 years
      of diagnosis, respectively. Risk of acute myocardial infarction (AMI) was
      similarly increased. The risk of CHF/CM and AMI was significantly higher in those
      patients with DLBCL (vs. controls) who did not report preexisting cardiovascular
      disease, compared to those who had preexisting cardiovascular disease; this was
      due to dose reductions of doxorubicin among patients with preexisting
      cardiovascular disease. Rituximab improved survival in patients with stage III-IV
      (but not I-II) disease (p-interaction = 0.0003). Our novel findings emphasize the
      need to reduce cardiac toxicity of doxorubicin in elderly DLBCL patients. 

PMID- 24893800
TI  - Two cases of myelofibrosis with severe thrombocytopenia and symptomatology
      successfully treated with combination of pomalidomide and ruxolitinib.

PMID- 24893798
TI  - Effects of long-term treatment with quercetin on cognition and mitochondrial
      function in a mouse model of Alzheimer's disease.
AB  - Amyloid-beta (Abeta)-induced mitochondrial dysfunction has been recognized as a
      prominent, early event in Alzheimer's disease (AD). Therefore, therapeutics
      targeted to improve mitochondrial function could be beneficial. Quercetin, a
      bioflavanoid, has been reported to have potent neuro-protective effects, but its
      preventive effects on Abeta-induced mitochondrial dysfunction and cognitive
      impairment have not been well characterised. Three-month-old APPswe/PS1dE9
      transgenic mice were randomly assigned to a vehicle group, two quercetin (either
      20 or 40 mg kg(-1) day(-1)) groups, or an Aricept (2 mg kg(-1) day(-1)) group.
      After 16 weeks of treatment, we observed beneficial effects of quercetin (40 mg
      kg(-1) day(-1)), including lessening learning and memory deficits, reducing
      scattered senile plaques, and ameliorating mitochondrial dysfunction, as
      evidenced by restoration of mitochondrial membrane potential, reactive oxygen
      species and ATP levels in mitochondria isolated from the hippocampus compared to
      control. Furthermore, the AMP-activated protein kinase (AMPK) activity
      significantly increased in the quercetin-treated (40 mg kg(-1) day(-1)) group.
      These findings suggest that a reduction in plaque burden and mitochondrial
      dysfunction through the activation of AMPK may be one of the mechanisms by which
      quercetin improves cognitive functioning in the APPswe/PS1dE9 transgenic mouse
      model of AD. 

PMID- 24893801
TI  - Edge strand engineering prevents native-like aggregation in Sulfolobus
      solfataricus acylphosphatase.
AB  - beta-proteins are constantly threatened by the risk of aggregation because beta
      sheets are inherently structured for edge-to-edge interactions. To avoid native
      like aggregation, evolution has resulted in a set of strategies that prevent
      intermolecular beta-interactions. Acylphosphatase from Sulfolobus solfataricus
      (Sso AcP) represents a suitable model for the study of such a process. Under
      conditions promoting aggregation, Sso AcP acquires a native-like conformational
      state whereby an unstructured N-terminal segment interacts with the edge beta
      strand B4 of an adjacent Sso AcP molecule. Because B4 is poorly protected against
      aggregation, this interaction triggers the aggregation cascade without the need
      for unfolding. Recently, three single Sso AcP mutants (V84D, Y86E and V84P) were
      designed to engineer additional protection against aggregation in B4 and were
      observed to successfully impair native-like aggregation in all three variants at
      the expense of a lower stability. To understand the structural basis of the
      reduced aggregation propensity and lower stability, the crystal structures of the
      Sso AcP variants were determined in the present study. Structural analysis
      reveals that the V84D and Y86E mutations exert protection by the insertion of an
      edge negative charge. A conformationally less regular B4 underlies protection
      against aggregation in the V84P mutant. The thermodynamic basis of instability is
      discussed. Moreover, kinetic experiments indicate that aggregation of the three
      mutants is not native-like and is independent of the interaction between B4 and
      the unstructured N-terminal segment. The reported data rationalize previous
      evidence regarding Sso AcP native-like aggregation and provide a basis for the
      design of aggregation-free proteins. DATABASE: The atomic coordinates and related
      experimental data for the Sso AcP mutants V84P, V84D, DeltaN11 Y86E have been
      deposited in the Protein Data Bank under accession numbers 4OJ3, 4OJG and 4OJH,
      respectively. STRUCTURED DIGITAL ABSTRACT: * Sso AcP and Sso AcP bind by
      fluorescence technology (View interaction).

PMID- 24893802
TI  - Leptomeningeal metastasis from hepatocellular carcinoma with other unusual
      metastases: a case report.
AB  - BACKGROUND: Leptomeningeal metastasis, which results from metastasis of tumors to
      the arachnoid and pia mater, can lead to the dissemination of tumor cells
      throughout the subarachnoid space via the cerebral spinal fluid, and frequently
      with a poor prognosis. The primary tumor in adults is most often breast cancer,
      lung cancer, or melanoma. Although leptomeningeal metastasis due to
      cholangiocarcinoma has been reported, to the best of our knowledge there is no
      cytologically confirmed report of leptomeningeal metastasis from hepatocellular
      carcinoma. CASE PRESENTATION: We herein report a case of leptomeningeal
      metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant
      systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous
      tissues, and abdominal pelvis. The neurological symptoms of the patient were
      relieved after treatment with methotrexate intra-cerebral spinal fluid
      chemotherapy concurrent with whole brain radiotherapy. CONCLUSION: To our
      knowledge this is the first report of leptomeningeal metastasis from
      hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra
      cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was
      effective.

PMID- 24893803
TI  - Cucurbitacin B induces DNA damage, G2/M phase arrest, and apoptosis mediated by
      reactive oxygen species (ROS) in leukemia K562 cells.
AB  - Cucurbitacin B (Cuc B) is a natural product with potent anti-cancer activities in
      solid tumors. We investigated the anti-cancer effect of Cuc B on K562 leukemia
      cells. Cuc B drastically decreased cell viability in a concentration-dependent
      manner. Cuc B treatment caused DNA damage, as shown by long tails in the comet
      assay and increased gammaH2AX protein expression. Immunofluorescence, Fluo3- AM,
      and JC-1 staining results showed that Cuc B treatment induced nuclear gammaH2AX
      foci, increased intracellular calcium ion concentration, and depolarized
      mitochondrial membrane potential (MMP), respectively. Cuc B induced G2/M phase
      arrest and apoptosis, as shown by flow cytometry, DNA fragmentation, and protein
      expression analyses. In addition, Cuc B dramatically increased intracellular
      reactive oxygen species (ROS) generation as measured by DCFH2-DA. N-acetyl-l
      cysteine pretreatment significantly reversed Cuc B-induced DNA damage, increased
      intracellular calcium ion concentration, and reduced MMP, G2/M phase arrest, and
      apoptosis. Taken together, these results suggested that ROS mediated Cuc B
      induced DNA damage, G2/M arrest, and apoptosis in K562 cells. This study provides
      novel mechanisms to better understand the underlying anti-cancer mechanisms of
      Cuc B. 

PMID- 24893804
TI  - Anti-proliferative activities of terpenoids isolated from Alisma orientalis and
      their structure-activity relationships.
AB  - This study aimed to isolate terpenoids from Alisma orientalis (Sam.) Juzep. and
      elucidate their antiproliferative activities, as well as structure-activity
      relationships. Fourteen protostane-type triterpenoids were isolated from the
      rhizome of A. orientalis. Among these triterpenoids, alisol A (1), alisol A 24
      acetate (2), alisol B (3), alisol B 23-acetate (4), and alisol G (8) presented
      inhibitory effects on cancer cell lines tested. Compounds 3 and 4 showed the
      highest potential; IC50 values for HepG2, MDA-MB-231, and MCF-7 cells were 16.28,
      14.47, and 6.66 MUM for 3 and 18.01, 15.97, and 13.56 MUM for 4, respectively.
      Based on these results, we concluded that the degree of C-16 oxidation and the
      double bond between C-13 and C-17 may be significant in anti-proliferative
      activities. Further study showed that 3 and 4 effectively induced apoptosis, as
      confirmed by flow cytometry. Increased intracellular calcium concentration and
      endoplasmic reticulum stress were detected after treatment with 4 in HepG2 cells.
      Although compounds 1 and 2 induced minimal apoptosis, they evidently delayed the
      G2/M phase in HepG2 cells. Further study showed that 1-4 also enhanced LC3II
      expression, indicating autophagy is occured. 

PMID- 24893805
TI  - Efficient and sensitive identification and quantification of airborne pollen
      using next-generation DNA sequencing.
AB  - Pollen monitoring is an important and widely used tool in allergy research and
      creation of awareness in pollen-allergic patients. Current pollen monitoring
      methods are microscope-based, labour intensive and cannot identify pollen to the
      genus level in some relevant allergenic plant groups. Therefore, a more
      efficient, cost-effective and sensitive method is needed. Here, we present a
      method for identification and quantification of airborne pollen using DNA
      sequencing. Pollen is collected from ambient air using standard techniques. DNA
      is extracted from the collected pollen, and a fragment of the chloroplast gene
      trnL is amplified using PCR. The PCR product is subsequently sequenced on a next
      generation sequencing platform (Ion Torrent). Amplicon molecules are sequenced
      individually, allowing identification of different sequences from a mixed sample.
      We show that this method provides an accurate qualitative and quantitative view
      of the species composition of samples of airborne pollen grains. We also show
      that it correctly identifies the individual grass genera present in a mixed
      sample of grass pollen, which cannot be achieved using microscopic pollen
      identification. We conclude that our method is more efficient and sensitive than
      current pollen monitoring techniques and therefore has the potential to increase
      the throughput of pollen monitoring. 

PMID- 24893806
TI  - Red emissive two-photon probe for real-time imaging of mitochondria trafficking.
AB  - Mitochondria trafficking plays an essential role for supplying energy in the
      neuronal system. We report here a red emissive two-photon probe for mitochondria
      (CMT-red) that showed high selectivity and robust staining ability for
      mitochondria, high photostability under a two-photon microscopy imaging
      condition, and low cytotoxicity. This probe can be easily loaded into live cells
      and tissue and used for real-time, high resolution imaging of the mitochondria
      trafficking in primary cortical neurons as well as in rat hippocampal tissue. 

PMID- 24893807
TI  - Theoretical study on the BF3-catalyzed Meinwald rearrangement reaction.
AB  - The mechanisms of the BF3-catalyzed Meinwald rearrangement reactions of five
      epoxides in dichloromethane solution have been studied at the M062X/6
      311++G(2df,2pd) level. Accordingly, the Lewis acid-epoxide complex can react
      through several alternative pathways, though three phases (ring opening, C-C bond
      rotation, and hydrogen or alkyl group migration) are required in any path. In
      some cases, a concerted pathway (involving all three successive phases) is found.
      Otherwise, the reaction takes place through a reaction mechanism involving a
      zwitterion or a BF3 addition compound (formed by fluoride transfer from the BF3
      moiety to the incipient carbocationic center generated by C-O bond rupture) or
      both as reaction intermediate(s). The BF2-bound fluorohydrin yields the reaction
      product through a concerted process involving fluoride transfer from the C-F bond
      to the OBF2 group and hydrogen or alkyl group migration, as first demonstrated in
      this work. Effects of a number of features (solvent effects, concurrent
      hydrogen/alkyl group migration, carbocation substitution, benzylic conjugation)
      are also discussed. 

PMID- 24893809
TI  - [Smarter hospital care].
AB  - The quality of hospital care is being questioned. This calls for decisions and
      innovations both in terms of care process and content. Innovations do not always
      have the desired effect and are often insufficiently supported by scientific
      evidence. The adoption and application of evidence-based principles in the
      organization as well as in the content of healthcare are therefore pivotal, not
      only for care professionals, but for hospital managers and decision makers as
      well. Implementation of these ideas appears most successful when conducted on
      different levels: national, strategic, tactical, and operational, and in
      educational as well as clinical settings. 

PMID- 24893808
TI  - Diagnostic accuracy of the BACs-on-BeadsTM assay versus karyotyping for prenatal
      detection of chromosomal abnormalities: a retrospective consecutive case series.
AB  - OBJECTIVE: To evaluate the diagnostic performance of the BACs-on-Beads(TM)
      (BoBs(TM)) assay for prenatal detection of chromosomal abnormalities. DESIGN:
      Retrospective study. SETTING: Tertiary prenatal diagnosis centre. POPULATION:
      Women referred for prenatal diagnosis. METHODS: We retrieved 2153 archived DNA
      samples collected between January 2010 and August 2011 for the BoBs(TM) assay.
      These samples had previously been tested by quantitative fluorescence polymerase
      chain reaction (QF-PCR) and karyotyping. In the BoBs(TM) assay a sample was
      defined as normal disomic when the ratio of the fluorescence intensities in a
      chromosome locus lay within the threshold (mean ratio +/- 2SD), and as deleted or
      duplicated when the ratio was below the lower threshold (0.6-0.8) or above the
      upper threshold (1.3-1.4), respectively. The BoBs(TM) results were further
      validated by microarray and compared in a blinded manner with the original QF-PCR
      and karyotyping results. MAIN OUTCOME MEASURES: Concordance of any numerical,
      structural, and submicroscopic chromosomal abnormalities between the methods.
      RESULTS: BACs-on-Beads(TM) was similar to karyotyping and QF-PCR in detecting
      trisomy 13, trisomy 18, trisomy 21, and sex chromosomal aneuploidies, and
      superior to QF-PCR in detecting major structural abnormalities (53.3 versus
      13.3%) and mosaicism (28.6 versus 0%) involving chromosomal abnormalities other
      than the common aneuploidies. BoBs(TM) detected six microdeletion syndromes
      missed by karyotyping and QF-PCR; however, BoBs(TM) missed two cases of triploidy
      identified by QF-PCR. Therefore, the sensitivity of BoBs(TM) is 96.7% (95% CI
      92.6-98.7%), and its specificity is 100% (95% CI 99.8-100%). CONCLUSIONS: BACs-on
      Beads(TM) can replace QF-PCR for triaging in prenatal diagnosis, and gives a
      better diagnostic yield than current rapid aneuploidy tests.

PMID- 24893810
TI  - [Microvascular angina in women: a diagnostic and therapeutic challenge].
AB  - Gender differences play an important role in coronary heart disease (CHD). Not
      only in the presentation of symptoms, but also in their underlying
      pathophysiology. Women with persistent angina without obstructive coronary artery
      disease (CAD) pose a diagnostic and therapeutic challenge. Half of these women
      have microvascular coronary dysfunction (MCD). The 2013 guidelines on management
      of stable angina now acknowledge this condition, but our understanding of MCD is
      still limited. In this clinical case presentation we elaborate on contemporary
      methods of diagnosing and managing microvascular angina based on the cases of two
      women who attended our outpatient clinic. The availability of non-invasive tools
      to diagnose MCD is still limited. Current treatment is based on reduction of
      cardiovascular risk factors but physicians and patients should be aware that
      although therapy usually reduces symptoms, they do not completely disappear. More
      research on diagnostic methods and effective therapy for MCD is eagerly awaited. 

PMID- 24893811
TI  - [A girl with desquamation of hands and feet].
AB  - A 3-year-old girl presented with desquamation of hands and feet, preceded by sore
      throat and subfebrile temperature. She developed exanthema with typical skip
      lesions and orange hyperkeratosis. The diagnosis 'classic juvenile pityriasis
      rubra pilaris' was made. The girl was successfully treated with acitretin. 

PMID- 24893812
TI  - [Treatment of trigeminal neuralgia].
AB  - Classic idiopathic trigeminal neuralgia is characterized by sharp unilateral
      shooting pain in the distribution of one or more branches of the trigeminal
      nerve. It involves a diagnosis of exclusion. Initially, therapy consists of
      medical therapy, preferably with carbamazepine or oxcarbazepine. For patients
      refractory to medical therapy, microvascular decompression of the trigeminal
      nerve provides the best long-term outcomes, at a relatively low complication
      risk. In case of surgical contraindications, there are other options:
      radiosurgery or a neurodestructive procedure of the trigeminal ganglion. Short
      term outcomes after neurodestructive therapy are good, however effects diminish
      over time. Every patient with idiopathic trigeminal neuralgia in whom medical
      therapy has failed, should be counselled at an experienced centre in which
      neurosurgical treatment is available.

PMID- 24893813
TI  - [Plain abdominal x-rays for the sake of the doctor].
AB  - Scientific research has demonstrated that the diagnostic accuracy of plain
      abdominal x-rays is lower than that of other imaging modalities such as CT or
      ultrasonography in patients with acute abdominal pain. Nevertheless, plain x-rays
      are continually being used in daily practice. There are several comparable
      examples in which the implementation of new evidence into clinical practice seems
      problematic. Apparently other factors such as the experience of the doctor and
      psychological processes make it difficult to translate clear scientific evidence
      into daily practice. 

PMID- 24893814
TI  - [Guideline 'Diagnostics in acute abdominal pain in adults'].
AB  - The interdisciplinary, evidence-based guideline 'Diagnostics in acute abdominal
      pain in adults' describes the optimal in-hospital diagnostic work-up of patients
      with acute abdominal pain. Amongst other recommendations, the guideline advises
      the use of C-reactive protein and white blood cell count to differentiate urgent
      from non-urgent causes in an adult with acute abdominal pain presenting at the
      Emergency Department. If there is clinical suspicion of an urgent condition the
      guideline advises that additional imaging be performed. The guideline states that
      conventional imaging (plain abdominal - or chest x-ray) is unnecessary as this is
      of no benefit. Additionally the guideline recommends that patients with acute
      abdominal pain and severe sepsis or septic shock are started on antibiotic
      treatment within an hour at the Emergency Department and not to wait for the
      diagnostic procedures to be completed.

PMID- 24893815
TI  - [Treatment of inflammatory bowel disease: what if drug therapy fails?].
AB  - The treatment of patients with chronic inflammatory bowel disease (IBD) in
      accordance with the current guideline is generally successful but there is still
      a group of patients for whom the medication does not work. If the initially
      prescribed medication is not sufficiently effective, the tendency is to move on
      to a 'higher' class of drugs relatively quickly. This is not always necessary. If
      therapy fails then therapy compliance and dosage should first be examined.
      Measurement of the metabolites of purine analogues can be helpful in determining
      the optimal drug dosage. The results sometimes show that a previously-prescribed
      drug may still be an option. Despite its proven efficacy, methotrexate appears to
      be being prescribed less often. For those patients who do not respond adequately
      to the optimum dosage of anti-tumour necrosis factor (TNF), there are new drugs
      on the way. Vedolizumab, a leukocyte adhesion inhibitor, in particular is showing
      promising results. 

PMID- 24893816
TI  - [Doctoral research by physicians: it goes without saying!].
AB  - It is important that junior doctors in training conduct research for a number of
      years, culminating in a PhD. This is crucial to their development as critical and
      versatile doctors, which is exactly what is required now, in 2014. Hospitals are
      keen to have doctors with a broad education, and conducting scientific research
      is an enrichment for the investigators themselves. It is not necessarily
      undesirable that they do this principally to increase their chances of trainee
      posts; even those who have almost completed a PhD can be rejected for trainee
      positions if they do not seem to be competent. 

PMID- 24893817
TI  - [Stop the compulsive PhD trajectory for junior doctors].
AB  - It has become the rule rather than the exception that junior doctors in training
      spend 3-4 years on a research project, culminating in a thesis. Without a PhD,
      clinical career prospects within and outside academia look rather bleak. Here I
      argue that PhD degrees should be pursued only by the most talented and motivated
      young clinicians. 

PMID- 24893818
TI  - [A 37-year-old woman with anogenital warts].
AB  - A 37-year-old woman, who had been suffering from Crohn's disease since twenty-two
      years, visited our dermatology outpatient clinic with complaints of wart-like
      lesions in the vulvar and perianal regions. On physical examination, nodules,
      plaques and tumours were seen. Histological examination showed features
      compatible with Crohn's disease. The diagnosis metastatic Crohn's disease was
      made. 

PMID- 24893819
TI  - [Dutch Health Care Inspectorate (IGZ) abuses its inspection authority in patient
      files].
AB  - For its investigation regarding the transfer of data after discharge of
      vulnerable elderly patients from hospital to nursing homes, care homes or home
      care, the Dutch Health Care Inspectorate (IGZ) demands access to patients' files,
      without their explicit consent. Doctors who do not cooperate run the risk of
      penalty payments. Since it concerns a limited number of patients per practice, it
      would not be unreasonably onerous for the Inspectorate to allow doctors to ask
      their patients' consent. Other reasons mentioned by the Inspectorate, such as
      possible "inappropriate correction" of data and the capability of vulnerable
      elderly patients to give their consent seem improper grounds to breach patients'
      right to privacy and to demand that doctors breach professional confidentiality.
      The legality of the Inspectorate's actions could be addressed in a test case and
      should be discussed more widely in light of the Inspectorate's work plan for
      2014. 

PMID- 24893820
TI  - Validation of reference genes for normalization of qPCR mRNA expression levels in
      Staphylococcus aureus exposed to osmotic and lactic acid stress conditions
      encountered during food production and preservation.
AB  - Staphylococcus aureus represents the most prevalent cause of food-borne
      intoxications worldwide. While being repressed by competing bacteria in most
      matrices, this pathogen exhibits crucial competitive advantages during growth at
      high salt concentrations or low pH, conditions frequently encountered in food
      production and preservation. We aimed to identify reference genes that could be
      used to normalize qPCR mRNA expression levels during growth of S. aureus in food
      related osmotic (NaCl) and acidic (lactic acid) stress adaptation models.
      Expression stability of nine housekeeping genes was evaluated in full (LB) and
      nutrient-deficient (CYGP w/o glucose) medium under conditions of osmotic (4.5%
      NaCl) and acidic stress (lactic acid, pH 6.0) after 2-h exposure. Among the set
      of candidate reference genes investigated, rplD, rpoB,gyrB, and rho were most
      stably expressed in LB and thus represent the most suitable reference genes for
      normalization of qPCR data in osmotic or lactic acid stress models in a rich
      medium. Under nutrient-deficient conditions, expression of rho and rpoB was
      highly stable across all tested conditions. The presented comprehensive data on
      changes in expression of various S. aureus housekeeping genes under conditions of
      osmotic and lactic acid stress facilitate selection of reference genes for qPCR
      based stress response models.

PMID- 24893822
TI  - Why is eusociality an almost exclusively terrestrial phenomenon?
AB  - Eusociality has evolved multiple times across diverse terrestrial taxa, and
      eusocial species fundamentally shape many terrestrial ecosystems. However,
      eusocial species are far less common and have much less ecological impact, in
      aquatic than terrestrial environments. Here, we offer a potential explanation for
      these observations. It appears that a precondition for the evolution of
      eusociality is the defence and repeated feeding of offspring in a nest or other
      protected cavity, and so eusocial species must be able to exploit a predator
      safe, long-lasting (multigenerational) expandable nest. We argue that a range of
      factors mean that opportunities for such nests are much more widespread and the
      advantages more compelling in terrestrial than aquatic ecosystems. 

PMID- 24893821
TI  - Long-term dosing patterns of enteric-coated mycophenolate sodium or mycophenolate
      mofetil with tacrolimus after renal transplantation.
AB  - MORE was a four-yr, prospective, observational study at 40 transplant centers in
      the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing
      over time in 904 de novo kidney transplant recipients receiving enteric-coated
      mycophenolate sodium (EC-MPS, n = 616) or mycophenolate mofetil (MMF, n = 288)
      with tacrolimus. Induction therapy and steroid treatment were similar in the two
      subpopulations. The proportion of patients receiving the maximal recommended MPA
      dose was 80.5%, 43.9%, 39.2%, 34.6%, and 30.1% at baseline and years 1, 2, 3, and
      4, respectively. More patients received the maximal recommended MPA dose with EC
      MPS vs. MMF at month 1 (79.2% vs. 71.7%, p = 0.016), month 3 (68.5% vs. 56.9%, p
      = 0.001), and month 6 (52.9% vs. 44.0%, p = 0.028). Multivariate analysis showed
      the risk of biopsy-proven acute rejection, graft loss or death to be similar for
      EC-MPS vs. MMF. Estimated glomerular filtration rate (GFR) was similar with EC
      MPS vs. MMF at all time points. There were no significant differences in any
      category of adverse event between the EC-MPS and MMF cohorts during follow-up,
      including gastrointestinal events. In conclusion, MPA dose was maintained more
      effectively in the first six months after kidney transplantation using EC-MPS vs.
      MMF, without an increase in adverse events. 

PMID- 24893823
TI  - Influence of dye content on the conduction band edge of titania in the steam
      treated dye-dispersing titania electrodes.
AB  - The titania and dye-dispersing titania electrodes were prepared by a nitric acid
      catalyzed sol-gel process. The dye-dispersing titania contains the dye molecules
      dispersed on the surface of the individual nanosized titania particles. The photo
      cyclic voltammetry (Photo-CV) and photoelectric measurements of the dye
      dispersing titania electrodes were conducted to clarify the factors changing the
      conduction band edge of the titania and the open-circuit voltage (Voc ) of the
      electrodes. The remaining nitrate ions caused a negative shift of conduction band
      edge of the titania of the dye-dispersing titania. The conduction band edge of
      the titania was shifted in a negative direction in the electrode containing a
      greater amount of the dye. These results are due to the adsorption of nitrate
      ions and the dye-titania complex formation on the titania particle surface. The
      effect of the dye-titania complex formation on the shift in the titania
      conduction band edge was greater than that of the adsorption of nitrate ions due
      to strong interaction between the dye and titania through the carboxylate and
      quinone-like groups of the dye. The shift in the titania conduction band edge
      corresponded to the change in the Voc value. 

PMID- 24893824
TI  - A Longitudinal View of the Association Between Therapist Warmth and Couples' In
      Session Process: An Observational Pilot Study of Emotionally Focused Couples
      Therapy.
AB  - This longitudinal dyadic clinical process study used coded data from eleven
      couples to determine the influence of therapist warmth behaviors on couples'
      warmth behaviors over time in therapy. A mixed effects model was used to examine
      within- and between-individual variability. Men and women were modeled
      separately. A series of two-level multilevel models of change were examined,
      where Time is Level 1 and Individual is Level 2. Findings were mixed. There was
      no significant relationship between therapist warmth toward wife and wife warmth
      toward husband; however, there was a significant relationship between therapist
      warmth toward husband and husband warmth toward wife. Findings demonstrated that
      62.9% of the variance in husband warmth toward wife was accounted for by
      therapist warmth to husband across time in therapy. Specifically, therapist
      warmth toward husband was significantly and positively related to husband warmth
      toward wife over time in therapy. Clinical implications and directions for future
      research are discussed. 

PMID- 24893825
TI  - Environmental determinants of type 1 diabetes: a role for overweight and insulin
      resistance.
AB  - Rates of type 1 diabetes are rising globally, with a decreasing proportion of
      high-risk genotypes and twin concordance rates below 50%. Therefore,
      environmental factors such as viruses, nutrition and overweight have been
      examined as putative aetiological agents. The accelerator hypothesis proposes
      that overweight and insulin resistance are central to both type 1 and type 2
      diabetes and may explain, in part, the rise in type 1 diabetes incidence. The
      temporal rise in body mass index at type 1 diabetes onset and the observation
      that pre-diabetic children are heavier and more insulin resistant than their
      peers suggests convergence of type 1 and type 2 diabetes phenotypes. The
      influence of insulin resistance may begin in utero, although the aetiological
      role of birthweight in type 1 diabetes remains unclear. Further research to
      elucidate the role of these modifiable risk factors in today's obesogenic
      environment may provide future potential for diabetes prevention. 

PMID- 24893826
TI  - Incidence of upper gastrointestinal haemorrhage in Maori and New Zealand European
      ethnic groups, 2001-2010.
AB  - BACKGROUND: To date no incidence figures for upper gastrointestinal haemorrhage
      (UGIH) in New Zealand have been published. AIMS: To determine the incidence of
      UGIH in a demographically defined population, and to assess variation in
      incidence associated with demographic parameters. METHODS: Between 17 March 2001
      and 12 October 2010, all patients presenting to Waikato Hospital with UGIH were
      prospectively ascertained, and clinical, epidemiological and laboratory data were
      collected. Incidence rates were calculated, and were age adjusted to the World
      Health Organization world standard population. Parameters associated with trends
      in incidence were examined. RESULTS: There were 1360 UGIH events, yielding a
      crude incidence of 59.2 per 100,000 adults (age >= 15 years) per year (all quoted
      incidence figures per 100,000 adults per year), and an age-adjusted incidence
      (AAI) of 46.4. AAI was higher for Maori compared with New Zealand Europeans (91.3
      vs 37.0, rate ratio (RR) = 2.47, P < 0.001). Maori were more likely to have a
      gastric ulcer at endoscopy (odds ratio (OR) = 2.21, P < 0.001). For those tested
      for Helicobacter pylori (n = 702), Maori were more likely to be infected (OR =
      2.12, P < 0.001). AAI was higher for males (61.1 vs 33.6, RR = 1.82, P < 0.001).
      Males were more likely to have a duodenal ulcer at endoscopy (OR = 1.79, P <
      0.001). AAI incidence decreased from the first to the second half of the study
      period (53.6 vs 45.8, RR = 1.17, P < 0.001). CONCLUSION: AAI of UGIH in the
      Waikato region was 46.4. This was significantly higher in Maori and in males, and
      decreased over the study period. These data will provide a comparison for future
      assessment of trends in UGIH.

PMID- 24893827
TI  - Rare chromosomal, genetic, and epigenetic-related risks associated with
      infertility treatment.
AB  - This article reviews the rarer chromosomal, genetic, and epigenetic-related risks
      of adverse child outcomes associated with infertility and its treatment. Excess
      structural chromosomal anomalies have been found in both male and female partners
      undergoing infertility treatment, and these risk direct transmission to
      offspring. Microdeletions of the Y-chromosome associated with male infertility
      have been transmitted to sons following treatment with intracytoplasmic sperm
      injection. It is thus possible that male offspring of men with infertility could
      experience fertility problems in adulthood. Infertility treatment for men with
      cystic fibrosis, or with congenital bilateral absence of the vas deferens in the
      absence of cystic fibrosis, who have azoospermia is now possible using surgically
      retrieved sperm. Transmission of known cystic fibrosis mutations can be avoided
      by testing the female partner prior to treatment and offering pre-implantation
      genetic diagnosis if she is a carrier. The effect of infertility and its
      treatment on genomic imprinting is of increasing concern as our understanding of
      the mechanisms of imprinting in germ cell development and embryogenesis expands.
      At present, it is far from clear whether there are longstanding effects of
      infertility per se or of its treatment on the health of adults who were conceived
      following assisted reproductive technologies, but available data suggest that
      this should be of concern and long-term follow-up studies are required. 

PMID- 24893828
TI  - Immuno-PCI: a proposal for the implementation of "seed and soil" concept in the
      treatment of peritoneal carcinomatosis from colorectal cancer.
AB  - The advent of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      has revolutionized the approach to peritoneal carcinomatosis of colorectal cancer
      origin in appropriately selected cases. However, the high postoperative morbidity
      and mortality following the procedure underlines the need for optimizing the
      patient selection criteria, finally aiming to establish a patient-tailored
      approach. The introduction of tools enabling the quantification of the peritoneal
      spread of the metastatic deposits has been of paramount importance in the
      decision-making and the estimation of the prognosis. However, we believe that it
      is high time to attempt a further evolution of the current practice, by
      incorporating in the above mentioned quantification scores parameters indicative
      of the immune-response against the disease progression, fact which will probably
      reflect more accurately the dynamics of cancer progression and will sequentially
      be a crucial step towards individualized treatment of peritoneal carcinomatosis. 

PMID- 24893829
TI  - Can we increase the yield of FDG-PET in the preoperative work-up for epilepsy
      surgery?
AB  - PURPOSE: [(18)F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a
      semi-invasive, interictal method of localization of hypometabolic epileptic foci.
      FDG-PET can be useful in the clinical work-up prior to epilepsy surgery,
      especially in equivocal cases. We investigated whether we could increase the
      yield of presurgical FDG-PET in patients with difficult epilepsy requiring
      chronic subdural electrocorticography (ECoG). METHODS: We retrospectively studied
      patients with refractory focal epilepsy in whom there was uncertainty about the
      focus localization and who underwent FDG-PET and ECoG. Two experts
      (epileptologist and nuclear medicine radiologist) together systematically re
      assessed the scans visually (PETRE), blinded to their initial reports. Scans were
      also re-analyzed by comparing them to a normal control dataset with Statistical
      Parametric Mapping (SPM), using a liberal (PETSPM1), and strict (PETSPM2)
      statistical threshold. Regions with hypometabolism and regions containing the
      seizure onset zone (SOZ) in ECoG were marked as positive anatomical regions
      (PARs). We compared the concordance of these PARs for the different PET re
      assessments. We calculated the sensitivity, specificity and accuracy of the PET
      results for the SOZ. The added value of the re-assessments was evaluated with
      emphasis on scans initially reported as negative. RESULTS: 41 Patients (63% extra
      temporal) were included. PETRE identified the SOZ best, with a sensitivity of 62%
      and specificity of 93%. PETSPM1 had a sensitivity of 62% and specificity 69%, for
      PETSPM2 this was 35% and 85% respectively. The overlap between PETRE vs. PETSPM1
      and vs. PETSPM2 was 71% and 37%. Visual re-assessment and PETSPM1 identified the
      SOZ in four out of five scans that were initially reported as negative.
      CONCLUSIONS: Pre-surgical re-assessment of PET scans is worthwhile in epilepsy
      patients who undergo ECoG, especially when results were reported as negative
      before. Visual re-assessment itself has a higher combined specificity,
      sensitivity and accuracy than SPM analysis alone. SPM analysis could be used as a
      guide for visual (re-)assessment, because of its high sensitivity.

PMID- 24893831
TI  - Evidence for increased visual gamma responses in photosensitive epilepsy.
AB  - BACKGROUND: A sustained gamma (30-70 Hz) oscillation induced in occipital cortex
      by high-contrast visual stimulation has been well characterised in animal local
      field potential recordings and in healthy human participants using
      magnetoencephalography (MEG). The spatial frequency of a static grating stimulus
      that gives maximal gamma is also that most likely to provoke seizures in
      photosensitive epilepsy. METHODS: We used MEG to study visual responses induced
      by grating stimuli of varying contrast and size in twelve patients with
      photosensitive epilepsy and two matched control groups, one with epilepsy but no
      photosensitivity, the other healthy controls. We used a beamformer approach to
      localise cortical responses and to characterise the time-frequency dynamics of
      evoked and induced oscillatory responses. RESULTS: A greater number of patients
      with photosensitivity had particularly amplitude gamma responses compared to
      controls. Formal statistical testing failed to find a group difference. One
      photosensitive patient, tested before and after sodium valproate, had a peak
      gamma amplitude when drug naive over four times larger than the group mean for
      controls; this high amplitude was substantially decreased after treatment with
      sodium valproate. We found no difference in the frequency of the sustained gamma
      response between the three groups. DISCUSSION: Altered power, but not frequency,
      in induced cortical responses to a static grating stimulus may be a
      characteristic of photosensitive epilepsy. Our failure to find a group difference
      on statistical testing may have been due to a wide intersubject variability and
      heterogeneity of the photosensitive group. A high amplitude response would be in
      keeping with previous evidence of altered contrast gain and increased spatial
      recruitment in photosensitive epilepsy.

PMID- 24893830
TI  - Vascular function and risk factors in children with epilepsy: associations with
      sodium valproate and carbamazepine.
AB  - AIM: To investigate biochemical cardiovascular risk factors and vascular
      endothelial function and structure in children with epilepsy on antiepileptic
      drugs (AEDs), particularly sodium valproate (VPA) and carbamazepine (CBZ).
      BACKGROUND: Individuals with epilepsy have increased risk factors for vascular
      disease, particularly lipid abnormalities and elevated total plasma
      homocyst(e)ine (tHcy). AED induced B-vitamin deficiencies have been suggested to
      contribute to this risk. Vitamin B supplementation has consequently been
      recommended for children on AEDs. Early vascular endothelial dysfunction and
      atherosclerosis are detectable by measuring flow-mediated dilation (FMD) and
      intima-media thickness (IMT). METHODS: Thirty children with epilepsy on AEDs
      (13.3+/-2.3 years, 14 male) and 30 controls (13.9+/-2.9 years, 14 male) were
      recruited. Fasting tHcy, folate, pyridoxal-5-phosphate (PLP), vitamin B12,
      glucose and lipids were measured. Vascular function and structure were assessed
      using FMD (brachial artery) and IMT (carotid/aortic arteries). RESULTS: No
      differences were found between children with epilepsy and controls for tHcy,
      folate, PLP, lipids, FMD, carotid or aortic IMT. Vitamin B12 levels were elevated
      and glucose reduced in children treated with VPA. Elevated total cholesterol,
      cholesterol/HDL ratio and triglycerides occurred in children treated with CBZ.
      Aortic IMT correlated with weight (r=0.75, p<0.001), BMI (r=0.54, p=0.01), and
      HDL cholesterol (r=-0.58, p=0.006). CONCLUSION: We found no early changes in
      vascular function or structure in children on valproate or carbamazepine. We were
      also unable to confirm previous reports of tHcy abnormalities in this group. This
      may be due to higher B-vitamin intake, which compensates for loss of vitamins
      induced by this AED therapy. Vitamin supplementation in children with epilepsy on
      valproate and carbamazepine is not required in populations with adequate dietary
      intake of B vitamins.

PMID- 24893832
TI  - A system of equations to approximate the pharmacokinetic parameters of lacosamide
      at steady state from one plasma sample.
AB  - PURPOSE: Frequent plasma sampling to monitor pharmacokinetic (PK) profile of
      antiepileptic drugs (AEDs), is invasive, costly and time consuming. For drugs
      with a well-defined PK profile, such as AED lacosamide, equations can accurately
      approximate PK parameters from one steady-state plasma sample. METHODS: Equations
      were derived to approximate steady-state peak and trough lacosamide plasma
      concentrations (Cpeak,ss and Ctrough,ss, respectively) and area under
      concentration-time curve during dosing interval (AUCtau,ss) from one plasma
      sample. Lacosamide (ka: ~2 h(-1); ke: ~0.05 h(-1), corresponding to half-life of
      13 h) was calculated to reach Cpeak,ss after ~1 h (tmax,ss). Equations were
      validated by comparing approximations to reference PK parameters obtained from
      single plasma samples drawn 3-12h following lacosamide administration, using data
      from double-blind, placebo-controlled, parallel-group PK study. Values of
      relative bias (accuracy) between -15% and +15%, and root mean square error (RMSE)
      values<=15% (precision) were considered acceptable for validation. RESULTS:
      Thirty-five healthy subjects (12 young males; 11 elderly males, 12 elderly
      females) received lacosamide 100mg/day for 4.5 days. Equation-derived PK values
      were compared to reference mean Cpeak,ss, Ctrough,ss and AUCtau,ss values.
      Equation-derived PK data had a precision of 6.2% and accuracy of -8.0%, 2.9%, and
      -0.11%, respectively. Equation-derived versus reference PK values for individual
      samples obtained 3-12h after lacosamide administration showed correlation (R2)
      range of 0.88-0.97 for AUCtau,ss. Correlation range for Cpeak,ss and Ctrough,ss
      was 0.65-0.87. Error analyses for individual sample comparisons were independent
      of time. CONCLUSION: Derived equations approximated lacosamide Cpeak,ss,
      Ctrough,ss and AUCtau,ss using one steady-state plasma sample within validation
      range. Approximated PK parameters were within accepted validation criteria when
      compared to reference PK values.

PMID- 24893834
TI  - Multiscale reconstruction algorithm for compressed sensing.
AB  - Compressed sensing (CS) method has attracted increasing attention owing to
      providing a novel insight for signal and image processing technology. Acquiring
      high-quality reconstruction results plays a crucial role in successful
      applications of CS method. This paper presents a multiscale reconstruction model
      that simultaneously considers the inaccuracy properties on the measurement data
      and the measurement matrix. Based on the wavelet analysis method, the original
      inverse problem is decomposed into a sequence of inverse problems, which are
      solved successively from the largest scale to the original scale. An objective
      functional, that integrate the beneficial advantages of the least trimmed sum of
      absolute deviations (LTA) estimation and the combinational M-estimation, is
      proposed. An iteration scheme that incorporates the advantages of the homotopy
      method and the evolutionary programming (EP) algorithm is designed for solving
      the proposed objective functional. Numerical simulations are implemented to
      validate the feasibility of the proposed reconstruction method. 

PMID- 24893833
TI  - Electroencephalographic features of familial spontaneous epileptic cats.
AB  - A feline strain of familial spontaneous epileptic cats (FSECs) with typical
      limbic seizures was identified in 2010, and have been maintained as a novel
      animal model of genetic epilepsy. In this study, we characterized the
      electroencephalographic (EEG) features of FSECs. On scalp EEG under sedation,
      FSECs showed sporadic, but comparatively frequent interictal discharges
      dominantly in the uni- or bilateral temporal region. Bemegride activation was
      performed in order to evaluate the predisposition of epileptogenicity of FSECs.
      The threshold doses of the first paroxysmal discharge, clinical myoclonus and
      generalized convulsion in FSECs were significantly lower than those in control
      cats. Chronic video-intracranial EEG monitoring revealed subclinical or clinical
      focal seizures with secondarily generalization onset from the unilateral amygdala
      and/or hippocampus. Clinical generalized seizures were also recorded, but we were
      unable to detect the onset site. The results of the present study show that FSECs
      resemble not only feline kindling or the kainic acid model and El mouse, but also
      human familial or sporadic mesial temporal lobe epilepsy. In addition, our
      results indicate that FSECs are a natural and valuable model of mesial temporal
      lobe epilepsy. 

PMID- 24893835
TI  - Cuckoo search algorithm based satellite image contrast and brightness enhancement
      using DWT-SVD.
AB  - This paper presents a new contrast enhancement approach which is based on Cuckoo
      Search (CS) algorithm and DWT-SVD for quality improvement of the low contrast
      satellite images. The input image is decomposed into the four frequency subbands
      through Discrete Wavelet Transform (DWT), and CS algorithm used to optimize each
      subband of DWT and then obtains the singular value matrix of the low-low
      thresholded subband image and finally, it reconstructs the enhanced image by
      applying IDWT. The singular value matrix employed intensity information of the
      particular image, and any modification in the singular values changes the
      intensity of the given image. The experimental results show superiority of the
      proposed method performance in terms of PSNR, MSE, Mean and Standard Deviation
      over conventional and state-of-the-art techniques. 

PMID- 24893837
TI  - Assessment of ovarian cancer spheroid attachment and invasion of mesothelial
      cells in real time.
AB  - Ovarian cancers metastasize by shedding into the peritoneal fluid and dispersing
      to distal sites within the peritoneum. Monolayer cultures do not accurately model
      the behaviors of cancer cells within a nonadherent environment, as cancer cells
      inherently aggregate into multicellular structures which contribute to the
      metastatic process by attaching to and invading the peritoneal lining to form
      secondary tumors. To model this important stage of ovarian cancer metastasis,
      multicellular aggregates, or spheroids, can be generated from established ovarian
      cancer cell lines maintained under nonadherent conditions. To mimic the
      peritoneal microenvironment encountered by tumor cells in vivo, a spheroid
      mesothelial co-culture model was established in which preformed spheroids are
      plated on top of a human mesothelial cell monolayer, formed over an extracellular
      matrix barrier. Methods were then developed using a real-time cell analyzer to
      conduct quantitative real time measurements of the invasive capacity of different
      ovarian cancer cell lines grown as spheroids. This approach allows for the
      continuous measurement of invasion over long periods of time, which has several
      advantages over traditional endpoint assays and more laborious real time
      microscopy image analyses. In short, this method enables a rapid, determination
      of factors which regulate the interactions between ovarian cancer spheroid cells
      invading through mesothelial and matrix barriers over time. 

PMID- 24893840
TI  - Infant and Young Child Feeding in Emergencies.

PMID- 24893839
TI  - Purification of the cystic fibrosis transmembrane conductance regulator protein
      expressed in Saccharomyces cerevisiae.
AB  - Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein
      cause cystic fibrosis (CF), an autosomal recessive disease that currently limits
      the average life expectancy of sufferers to <40 years of age. The development of
      novel drug molecules to restore the activity of CFTR is an important goal in the
      treatment CF, and the isolation of functionally active CFTR is a useful step
      towards achieving this goal. We describe two methods for the purification of CFTR
      from a eukaryotic heterologous expression system, S. cerevisiae. Like prokaryotic
      systems, S. cerevisiae can be rapidly grown in the lab at low cost, but can also
      traffic and posttranslationally modify large membrane proteins. The selection of
      detergents for solubilization and purification is a critical step in the
      purification of any membrane protein. Having screened for the solubility of CFTR
      in several detergents, we have chosen two contrasting detergents for use in the
      purification that allow the final CFTR preparation to be tailored to the
      subsequently planned experiments. In this method, we provide comparison of the
      purification of CFTR in dodecyl-beta-D-maltoside (DDM) and 1-tetradecanoyl-sn
      glycero-3-phospho-(1'-rac-glycerol) (LPG-14). Protein purified in DDM by this
      method shows ATPase activity in functional assays. Protein purified in LPG-14
      shows high purity and yield, can be employed to study post-translational
      modifications, and can be used for structural methods such as small-angle X-ray
      scattering and electron microscopy. However it displays significantly lower
      ATPase activity.

PMID- 24893838
TI  - Analysis of translation initiation during stress conditions by polysome
      profiling.
AB  - Precise control of mRNA translation is fundamental for eukaryotic cell
      homeostasis, particularly in response to physiological and pathological stress.
      Alterations of this program can lead to the growth of damaged cells, a hallmark
      of cancer development, or to premature cell death such as seen in
      neurodegenerative diseases. Much of what is known concerning the molecular basis
      for translational control has been obtained from polysome analysis using a
      density gradient fractionation system. This technique relies on
      ultracentrifugation of cytoplasmic extracts on a linear sucrose gradient. Once
      the spin is completed, the system allows fractionation and quantification of
      centrifuged zones corresponding to different translating ribosomes populations,
      thus resulting in a polysome profile. Changes in the polysome profile are
      indicative of changes or defects in translation initiation that occur in response
      to various types of stress. This technique also allows to assess the role of
      specific proteins on translation initiation, and to measure translational
      activity of specific mRNAs. Here we describe our protocol to perform polysome
      profiles in order to assess translation initiation of eukaryotic cells and
      tissues under either normal or stress growth conditions. 

PMID- 24893836
TI  - Three midlife strategies to prevent cognitive impairment due to Alzheimer's
      disease.
AB  - The slow, progressive accumulation of pathology characteristic of Alzheimer's
      disease is the principal determinant of cognitive decline leading to dementia.
      Risk-reduction strategies during midlife focus on raising the clinical threshold
      for the appearance of cognitive symptoms and on reducing the extent of Alzheimer
      pathology. Best available evidence suggests an approach based on three,
      conceptually distinct strategies. (1) Raise the threshold for cognitive symptoms
      by improving brain health. To achieve this goal, the tactic is to reduce
      cerebrovascular risks mediated by hypertension, diabetes, cigarette smoking, and
      hyperlipidemia. (2) Raise the threshold for cognitive symptoms by enhancing
      cognitive reserve. Here, tactics focus on mental stimulation associated with
      occupation, leisure activities and social engagement. (3) Reduce the burden of
      Alzheimer pathology. The most promising tactic toward this end is regular aerobic
      exercise. Tactics in support of strategies to reduce cognitive impairment due to
      Alzheimer pathology are not yet substantiated by robust, consistent clinical
      trial evidence. There is pressing need for well-designed pragmatic trials to
      provide stronger evidence on preventive strategies for late-life cognitive
      decline and dementia.

PMID- 24893841
TI  - Quasi one dimensional Dirac electrons on the surface of Ru2Sn3.
AB  - We present an ARPES study of the surface states of Ru2Sn3, a new type of a strong
      3D topological insulator (TI). In contrast to currently known 3D TIs, which
      display two-dimensional Dirac cones with linear isotropic dispersions crossing
      through one point in the surface Brillouin Zone (SBZ), the surface states on
      Ru2Sn3 are highly anisotropic, displaying an almost flat dispersion along certain
      high-symmetry directions. This results in quasi-one dimensional (1D) Dirac
      electronic states throughout the SBZ that we argue are inherited from features in
      the bulk electronic structure of Ru2Sn3 where the bulk conduction bands are
      highly anisotropic. Unlike previous experimentally characterized TIs, the
      topological surface states of Ru2Sn3 are the result of a d-p band inversion
      rather than an s-p band inversion. The observed surface states are the
      topological equivalent to a single 2D Dirac cone at the surface Brillouin zone. 

PMID- 24893843
TI  - Halogen-bonded mesogens direct polymer self-assemblies up to millimetre length
      scale.
AB  - Aligning polymeric nanostructures up to macroscale in facile ways remains a
      challenge in materials science and technology. Here we show polymeric self
      assemblies where nanoscale organization guides the macroscopic alignment up to
      millimetre scale. The concept is shown by halogen bonding mesogenic 1
      iodoperfluoroalkanes to a star-shaped ethyleneglycol-based polymer, having
      chloride end-groups. The mesogens segregate and stack parallel into aligned
      domains. This leads to layers at ~10 nm periodicity. Combination of
      directionality of halogen bonding, mesogen parallel stacking and minimization of
      interfacial curvature translates into an overall alignment in bulk and films up
      to millimetre scale. Upon heating, novel supramolecular halogen-bonded polymeric
      liquid crystallinity is also shown. As many polymers present sites capable of
      receiving halogen bonding, we suggest generic potential of this strategy for
      aligning polymer self-assemblies.

PMID- 24893842
TI  - Different rectal toxicity tolerance with and without simultaneous conventionally
      fractionated pelvic lymph node treatment in patients receiving hypofractionated
      prostate radiotherapy.
AB  - PURPOSE: To investigate added morbidity associated with the addition of pelvic
      elective nodal irradiation (ENI) to hypofractionated radiotherapy to the
      prostate. METHODS AND MATERIALS: Two-hundred twelve patients, treated with
      hypofractionated radiotherapy to the prostate between 2004 and 2011, met the
      inclusion criteria for the analysis. All patients received 70 Gy to the prostate
      delivered over 28 fractions and 103 (49%) received ENI consisting of 50.4 Gy to
      the pelvic lymphatics delivered simultaneously in 1.8 Gy fractions. The mean dose
      volume histograms were compared between the two subgroups defined by use of ENI,
      and various dose-volume parameters were analyzed for effect on late lower
      gastrointestinal (GI) and genitourinary (GU) toxicity. RESULTS: Acute grade 2
      lower GI toxicity occurred in 38 (37%) patients receiving ENI versus 19 (17%) in
      those who did not (p = 0.001). The Kaplan-Meier estimate of grade >= 2 lower GI
      toxicity at 3 years was 15.3% for patients receiving ENI versus 5.3% for those
      who did not (p = 0.026). Each rectal isodose volume was increased for patients
      receiving ENI up to 50 Gy (p <= 0.021 for each 5 Gy increment). Across all
      patients, the absolute V70 of the rectum was the only predictor of late GI
      toxicity. When subgroups, defined by the use of ENI, were analyzed separately,
      rectal V70 was only predictive of late GI toxicity for patients who received ENI.
      For patients receiving ENI, V70 > 3 cc was associated with an increased risk of
      late GI events. CONCLUSIONS: Elective nodal irradiation increases the rates of
      acute and late GI toxicity when delivered simultaneously with hypofractioanted
      prostate radiotherapy. The use of ENI appears to sensitize the rectum to hot
      spots, therefore we recommend added caution to minimize the volume of rectum
      receiving 100% of the prescription dose in these patients.

PMID- 24893844
TI  - Overexpression of GmAKT2 potassium channel enhances resistance to soybean mosaic
      virus.
AB  - BACKGROUND: Soybean mosaic virus (SMV) is the most prevalent viral disease in
      many soybean production areas. Due to a large number of SMV resistant loci and
      alleles, SMV strains and the rapid evolution in avirulence/effector genes,
      traditional breeding for SMV resistance is complex. Genetic engineering is an
      effective alternative method for improving SMV resistance in soybean. Potassium
      (K+) is the most abundant inorganic solute in plant cells, and is involved in
      plant responses to abiotic and biotic stresses. Studies have shown that altering
      the level of K+ status can reduce the spread of the viral diseases. Thus K+
      transporters are putative candidates to target for soybean virus resistance.
      RESULTS: The addition of K+ fertilizer significantly reduced SMV incidence.
      Analysis of K+ channel gene expression indicated that GmAKT2, the ortholog of
      Arabidopsis K+ weak channel encoding gene AKT2, was significantly induced by SMV
      inoculation in the SMV highly-resistant genotype Rsmv1, but not in the
      susceptible genotype Ssmv1. Transgenic soybean plants overexpressing GmAKT2 were
      produced and verified by Southern blot and RT-PCR analysis. Analysis of K+
      concentrations on different leaves of both the transgenic and the wildtype
      (Williams 82) plants revealed that overexpression of GmAKT2 significantly
      increased K+ concentrations in young leaves of plants. In contrast, K+
      concentrations in the old leaves of the GmAKT2-Oe plants were significantly lower
      than those in WT plants. These results indicated that GmAKT2 acted as a K+
      transporter and affected the distribution of K+ in soybean plants. Starting from
      14 days after inoculation (DAI) of SMV G7, severe mosaic symptoms were observed
      on the WT leaves. In contrast, the GmAKT2-Oe plants showed no symptom of SMV
      infection. At 14 and 28 DAI, the amount of SMV RNA in WT plants increased 200-
      and 260- fold relative to GmAKT2-Oe plants at each time point. Thus, SMV
      development was significantly retarded in GmAKT2-overexpressing transgenic
      soybean plants. CONCLUSIONS: Overexpression of GmAKT2 significantly enhanced SMV
      resistance in transgenic soybean. Thus, alteration of K+ transporter expression
      is a novel molecular approach for enhancing SMV resistance in soybean.

PMID- 24893845
TI  - Resveratrol: a supplementation for men or for mice?
AB  - Resveratrol is a polyphenolic compound found in several plants. In the last
      decades, the interest in this compound has enormously increased after benefits on
      metabolism and increased lifespan of various organisms have been reported with
      its supplementation. Several in-vitro and animal studies have observed that
      resveratrol can act on multiple molecular targets, including sirtuins, a class of
      NAD+ -dependent deacetylases. Despite the enthusiastic results reported in many
      animal- and in-vitro studies, few trials have been performed in humans with
      contrasting results. These conflicting data may be due at least in part to
      differences in the characteristics of the patients enrolled, the dosages and the
      duration of supplementation. Furthermore, many questions remain still unsolved,
      such as the dose or the duration of treatment to maximize its effects, the
      bioavailability of resveratrol and the role of food matrix to improve its
      bioactivity.In conclusion, at present the use of resveratrol as a supplement is
      not yet justified by the existing evidence.

PMID- 24893847
TI  - Preparation of Pt-Tl clusters showing new geometries. X-ray, NMR and luminescence
      studies.
AB  - Square planar complexes [Pt(CNC)L] (CNC = C,N,C-2,6-NC5H3(C6H4-2)2; L = tht
      (tetrahydrothiophene, SC4H8, 1), L = CN(t)Bu (2)) react with TlPF6 in different
      Pt/Tl molar ratios (3/1 in the case of 1 and 1/1 in the case of 2) yielding the
      complexes [{Pt(CNC)(tht)}3Tl](PF6) (3) and [Pt(CNC)(CN(t)Bu)Tl](PF6) (4),
      respectively. The structures of 3 and 4 (X-ray) show the presence of Pt->Tl
      dative bonds unsupported by any bridging ligands. In complex 3, the only Tl
      centre is simultaneously bonded to three Pt atoms forming a perfect equilateral
      triangle with Pt-Tl distances of 2.9088(5) A, remarkably short. Complex 4 is
      formed by three "Pt(CNC)(CN(t)Bu)Tl" units, disposed in a triangular fashion,
      linked together through eta(6)-Tl-arene interactions, and showing Pt-Tl bonds
      with distances of ca. 3.04 A. The study of these crystal structures would seem to
      indicate that the difference between the Pt/Tl ratios found in the complexes 3
      and 4 is due to the steric requirements of the L ligand bonded to Pt. NMR studies
      both in solution and in the solid state show that the Pt-Tl bond persists in
      solutions of 3 and 4. The UV-vis spectra of 3 and 4 in solution display the same
      profiles as those of 1 and 2, which may suggest a partial dissociation of the Pt
      Tl bond in solution. However, by DFT calculations it was proved that in this case
      the formation of the Pt-Tl dative bond does not produce the expected blue-shift
      in the UV-vis absorptions. The emissive behaviour of 1-4 in the solid state and
      in frozen solutions is also studied and included in this work.

PMID- 24893846
TI  - New type of SSUrDNA sequence was detected from both Plasmodium ovale curtisi and
      Plasmodium ovale wallikeri samples.
AB  - BACKGROUND: Plasmodium ovale is relatively unfamiliar to Chinese staff engaged in
      malaria diagnosis. In 2013, dried blood spots of four unidentified but suspected
      ovale malaria samples were sent to the National Malaria Reference Laboratory
      (NMRL) for reconfirmation. METHODS: Partial and complete, small, subunit
      ribosomal DNA (SSU rDNA) sequences of four samples were obtained with PCR-cloning
      sequencing method. Obtained sequences were analyzed by aligning with each other
      and with nine SSU rDNA sequences of six known Plasmodium parasites. A
      phylogenetic tree was constructed based on complete SSU rDNA sequences and 12
      same gene sequences derived from six known Plasmodium parasites and three Babesia
      parasites. Primary structure of conservative and variable regions of variant
      sequences was determined also by comparing them with those of six known
      Plasmodium parasites. To confirm their existence in genome, they were redetected
      with primers matching their variable regions. PCR systems aimed to roughly detect
      any eukaryotes and prokaryotes respectively were also applied to search for other
      pathogens in one of four patients. RESULTS: Totally, 19 partial and 23 complete
      SSU rDNA sequences obtained from four samples. Except eight variant sequences,
      similarities among sequences from same DNA sample were in general high (more than
      98%). The phylogenetic analysis revealed that three cases were infected by P.
      ovale wallikeri and one by P. ovale curtisi. Four of the variant sequences which
      obtained from four samples relatively showed high similarities with each other
      (98.5%-100%). Identical variant sequences actually could be re-obtained from each
      DNA sample. Their primary structure of conservative and variable regions showed
      quite fit with that of six known Plasmodium parasites. The test for prokaryote
      pathogens showed negative and the tests for eukaryotes only found DNA sequences
      of Human and P. ovale parasites. CONCLUSION: Both P. ovale wallikeri and P. ovale
      curtisi infections are present in imported malaria cases of China. New type of
      partial SSU rDNA sequence which assumed to express in a certain life stage of P.
      ovale was obtained from both P. ovale wallikeri and P. ovale curtisi samples.
      This discovery would supply information and clues to identify and understand P.
      ovale parasites more accurately.

PMID- 24893848
TI  - Covalent assembly of a two-dimensional molecular "sponge" on a Cu(111) surface:
      confined electronic surface states in open and closed pores.
AB  - We present a new class of on-surface covalent reactions, formed between
      diborylene-3,4,9,10-tetraaminoperylene and trimesic acid on Cu(111), which gives
      rise to a porous 2D-'sponge'. This aperiodic network allowed the investigation of
      the dependence of electron confinement effects upon pore size, shape and even in
      partial confinement. 

PMID- 24893849
TI  - The Biomechanical Effect of Loading Speed on Metal-on-UHMWPE Contact Mechanics.
AB  - Ultra high molecular weight polyethylene (UHMWPE) is a material commonly used in
      total hip and knee joint replacements. Numerous studies have assessed the effect
      of its viscoelastic properties on phenomena such as creep, stress relaxation, and
      tensile stress. However, these investigations either use the complex 3D
      geometries of total hip and knee replacements or UHMWPE test objects on their
      own. No studies have directly measured the effect of vertical load application
      speed on the contact mechanics of a metal sphere indenting UHMWPE. To this end, a
      metal ball was used to apply vertical force to a series of UHMWPE flat plate
      specimens over a wide range of loading speeds, namely, 1, 20, 40, 60, 80, 100,
      and 120 mm/min. Pressure sensitive Fujifilm was placed at the interface to
      measure contact area. Experimental results showed that maximum contact force
      ranged from 3596 to 4520 N and was logarithmically related (R(2)=0.96) to loading
      speed. Average contact area ranged from 76.5 to 79.9 mm(2) and was linearly
      related (R(2)=0.56) to loading speed. Average contact stress ranged from 45.1 to
      58.2 MPa and was logarithmically related (R(2)=0.95) to loading speed. All UHMWPE
      specimens displayed a circular area of permanent surface damage, which did not
      disappear with time. This study has practical implications for understanding the
      contact mechanics of hip and knee replacements for a variety of activities of
      daily living. 

PMID- 24893850
TI  - The role of maternal screening in diagnosing congenital cytomegalovirus
      infections in highly immune populations.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most important
      infectious cause of central nervous system disease and hearing loss in children.
      AIMS: In this study, we aimed to investigate the role of maternal screening in
      early diagnosis of congenital infection in highly immune populations. METHODS: A
      total of 163 women were included in the study; 103 of the subjects were pregnant
      and were at full term. The other 60 women were not pregnant, and all were
      healthy. RESULTS: CMV IgG seropositivity among the pregnant and control groups
      was found to be 98.1% (101/103) and 98.3% (59/60), respectively, and high IgG
      avidity was found in all women who had IgG positivity. We did not find any
      primary CMV infection in the two groups. The recurrent infection rate was found
      to be 5.82% in the pregnant group and 3.33% in the control group. There were no
      significant differences between the pregnant and control women in terms of CMV
      excretion in urine samples (4.85 vs. 3.33%, respectively; P = 1.000) or CMV-DNA
      presence in serum samples (1.94 vs. 0.0%, respectively; P = 0.532). The presence
      of symptomatic infection was not observed in any of the 104 babies born from the
      103 pregnancies. CONCLUSIONS: According to our results, a maternal screening
      based approach would be useful for only a very small group that is at risk of
      primary infection. Considering the cost of the scan, a routine maternal-based
      screening program is unadvisable in developing societies, but it is necessary for
      studies of different cohort groups and infectious diseases.

PMID- 24893851
TI  - Award incentives to improve quality care in internal medicine.
AB  - INTRODUCTION: Award incentives encourage higher standards of personal
      performance, which closely reflects the quality of patient care. We report the
      development, implementation, and success of our internal medicine department
      awards program. MATERIALS AND METHODS: An anonymous pre award survey collected
      responses to understand the need for an awards program in our department. Five
      awards were celebrated. An anonymous post award survey collected responses to
      evaluate the effectiveness of the program. RESULTS: A total of 69% (175/253) of
      pre award survey responses were collected. Among those, 100% (175/175) agreed
      that employee recognition was important. 68% (119/175) felt that performance
      should be the deciding criteria for employee recognition. There was a winner in
      each award category. Post award survey showed 78% (102/130) agreed that the award
      ceremony incentivized them to increase quality of personal performance.
      CONCLUSION: In summary, we feel that this transparent, objective, and peer
      nominated awards program could serve as an incentivized model for healthcare
      providers to elevate the standards of personal performance, which in turn will
      benefit the advancement of patient care.

PMID- 24893852
TI  - Individual and interpersonal characteristics that influence male-dominated sexual
      decision-making and inconsistent condom use among married HIV serodiscordant
      couples in Gujarat, India: results from the positive Jeevan Saathi study.
AB  - Approximately 40 % of new infections occur among married women. No studies have
      examined the factors that may contribute to HIV transmission among HIV-negative
      wives in HIV serodiscordant relationships in Gujarat, India. In 2010, a cross
      sectional survey with 185 HIV serodiscordant, married couples (i.e. 185 HIV
      positive husbands and their 185 HIV-negative wives) in Gujarat was conducted.
      Socio-demographic, individual, and interpersonal characteristics of HIV-positive
      husbands and their HIV negative wives were examined. The association of these
      characteristics with inconsistent condom use and male-dominated sexual decision
      making, were examined using multivariate logistic regression analyses.
      Approximately 10 % of couples reported inconsistent condom use in the past 3
      months and 20 % reported intimate partner violence (IPV). Reports of IPV were
      associated with a higher odds of inconsistent condom use among HIV-positive
      husbands (aOR = 6.281). Husbands who reported having received couples counseling
      had a lower odds of male-dominated decision making about condom use (aOR =
      0.372). HIV-negative wives who reported sex communication had a lower odds of
      male-dominated decision making about condom use (aOR = 0.322) with their HIV
      positive husbands. Although condom use is a traditional measure of risk behavior,
      other factors that facilitate risk, such as male-dominated sexual decision-making
      need to be considered in analyses of risk.

PMID- 24893853
TI  - Expression of an amylosucrase gene in potato results in larger starch granules
      with novel properties.
AB  - MAIN CONCLUSION: Expression of amylosucrase in potato resulted in larger starch
      granules with rough surfaces and novel physico-chemical properties, including
      improved freeze-thaw stability, higher end viscosity, and better enzymatic
      digestibility. Starch is a very important carbohydrate in many food and non-food
      applications. In planta modification of starch by genetic engineering has
      significant economic and environmental benefits as it makes the chemical or
      physical post-harvest modification obsolete. An amylosucrase from Neisseria
      polysaccharea fused to a starch-binding domain (SBD) was introduced in two potato
      genetic backgrounds to synthesize starch granules with altered composition, and
      thereby to broaden starch applications. Expression of SBD-amylosucrase fusion
      protein in the amylose-containing potato resulted in starch granules with a rough
      surface, a twofold increase in median granule size, and altered physico-chemical
      properties including improved freeze-thaw stability, higher end viscosity, and
      better enzymatic digestibility. These effects are possibly a result of the
      physical interaction between amylosucrase and starch granules. The modified
      larger starches not only have great benefit to the potato starch industry by
      reducing losses during starch isolation, but also have an advantage in many food
      applications such as frozen food due to its extremely high freeze-thaw stability.

PMID- 24893854
TI  - Growth promotion and inhibition of the Amazonian wild rice species Oryza
      grandiglumis to survive flooding.
AB  - In Asian cultivated rice (Oryza sativa), distinct mechanisms to survive flooding
      are activated in two groups of varieties. Submergence-tolerant rice varieties
      possessing the SUBMERGENCE1A (SUB1A) gene display reduced growth during flash
      floods at the seedling stage and resume growth after the flood recedes, whereas
      deepwater rice varieties possessing the SNORKEL1 (SK1) and SNORKEL2 (SK2) genes
      display enhanced growth based on internodal elongation during prolonged
      submergence at the mature stage. In this study, we investigated the occurrence of
      these growth responses to submergence in the wild rice species Oryza
      grandiglumis, which is native to the Amazon floodplains. When subjected to
      gradual submergence, adult plants of O. grandiglumis accessions showed enhanced
      internodal elongation with rising water level and their growth response closely
      resembled that of deepwater varieties of O. sativa with high floating capacity.
      On the other hand, when subjected to complete submergence, seedlings of O.
      grandiglumis accessions displayed reduced shoot growth and resumed normal growth
      after desubmergence, similar to the response of submergence-tolerant varieties of
      O. sativa. Neither SUB1A nor the SK genes were detected in the O. grandiglumis
      accessions. These results indicate that the O. grandiglumis accessions are
      capable of adapting successfully to flooding by activating two contrasting
      mechanisms as the situation demands and that each mechanism of adaptation to
      flooding is not mediated by SUB1A or the SK genes.

PMID- 24893855
TI  - Intrinsically de-sialylated CD103(+) CD8 T cells mediate beneficial anti-glioma
      immune responses.
AB  - BACKGROUND: Cancer vaccines reproducibly cure laboratory animals and reveal
      encouraging trends in brain tumor (glioma) patients. Identifying parameters
      governing beneficial vaccine-induced responses may lead to the improvement of
      glioma immunotherapies. CD103(+) CD8 T cells dominate post-vaccine responses in
      human glioma patients for unknown reasons, but may be related to recent thymic
      emigrant (RTE) status. Importantly, CD8 RTE metrics correlated with beneficial
      immune responses in vaccinated glioma patients. METHODS: We show by flow
      cytometry that murine and human CD103(+) CD8 T cells respond better than their
      CD103(-) counterparts to tumor peptide-MHC I (pMHC I) stimulation in vitro and to
      tumor antigens on gliomas in vivo. RESULTS: Glioma responsive T cells from mice
      and humans both exhibited intrinsic de-sialylation-affecting CD8 beta. Modulation
      of CD8 T cell sialic acid with neuraminidase and ST3Gal-II revealed de
      sialylation was necessary and sufficient for promiscuous binding to and
      stimulation by tumor pMHC I. Moreover, de-sialylated status was required for
      adoptive CD8 T cells and lymphocytes to decrease GL26 glioma invasiveness and
      increase host survival in vivo. Finally, increased tumor ST3Gal-II expression
      correlated with clinical vaccine failure in a meta-analysis of high-grade glioma
      patients. CONCLUSIONS: Taken together, these findings suggest that de-sialylation
      of CD8 is required for hyper-responsiveness and beneficial anti-glioma activity
      by CD8 T cells. Because CD8 de-sialylation can be induced with exogenous enzymes
      (and appears particularly scarce on human T cells), it represents a promising
      target for clinical glioma vaccine improvement.

PMID- 24893856
TI  - Generation and characterization of a novel human IgG1 antibody against vascular
      endothelial growth factor receptor 2.
AB  - VEGF and its receptors, especially VEGFR2 (KDR), are known to play a critical
      role in angiogenesis under both physiological and pathological conditions,
      including cancer and angiogenic retinopathies. This study was aimed at developing
      a fully human IgG1 antibody (mAb-04) constructed from a phage-derived scFv,
      targeting the VEGF/VEGFR2 pathway. Firstly, an innovative transfection system,
      containing two recombinant expression vectors (pMH3 and pCApuro), were introduced
      into CHO-s cells and clones with higher yield selected accordingly. After an
      optimal fermentation condition was determined, fed-batch fermentation was
      performed in 5-L bioreactor with a final yield up to 60 mg/L. Further, cell
      proliferation, wound healing, transwell invasion, tube formation and chick embryo
      chorioallantoic membrane assays showed significant anti-angiogenic activity of
      mAb-04 in vitro and in vivo. In addition, the results of Western blotting
      indicated the ability of mAb-04 to inhibit VEGF-induced VEGFR2 signaling pathway.
      Finally, ADCC assay demonstrated that mAb-04 is capable of mediating tumor cell
      killing in presence of effector cells. This study has therefore proved that the
      full-length antibody targeting human VEGFR2 has potential clinical applications
      in the treatment of cancer and other diseases where pathological angiogenesis is
      involved. 

PMID- 24893857
TI  - Preclinical evaluation of IL2-based immunocytokines supports their use in
      combination with dacarbazine, paclitaxel and TNF-based immunotherapy.
AB  - Antibody-cytokine fusion proteins ("immunocytokines") represent a promising class
      of armed antibody products, which allow the selective delivery of potent pro
      inflammatory payloads at the tumor site. The antibody-based selective delivery of
      interleukin-2 (IL2) is particularly attractive for the treatment of metastatic
      melanoma, an indication for which this cytokine received marketing approval from
      the US Food and drug administration. We used the K1735M2 immunocompetent
      syngeneic model of murine melanoma to study the therapeutic activity of F8-IL2,
      an immunocytokine based on the F8 antibody in diabody format, fused to human IL2.
      F8-IL2 was shown to selectively localize at the tumor site in vivo, following
      intravenous administration, and to mediate tumor growth retardation, which was
      potentiated by the combination with paclitaxel or dacarbazine. Combination
      treatment led to a substantially more effective tumor growth inhibition, compared
      to the cytotoxic drugs used as single agents, without additional toxicity.
      Analysis of the immune infiltrate revealed a significant accumulation of CD4(+) T
      cells 24 h after the administration of the combination. The fusion proteins F8
      IL2 and L19-IL2, specific to the alternatively spliced extra domain A and extra
      domain B of fibronectin respectively, were also studied in combination with tumor
      necrosis factor (TNF)-based immunocytokines. The combination treatment was
      superior to the action of the individual immunocytokines and was able to
      eradicate neoplastic lesions after a single intratumoral injection, a procedure
      that is being clinically used for the treatment of Stage IIIC melanoma.
      Collectively, these data reinforce the rationale for the use of IL2-based
      immunocytokines in combination with cytotoxic agents or TNF-based immunotherapy
      for the treatment of melanoma patients. 

PMID- 24893858
TI  - B7-H1 signaling is integrated during CD8(+) T cell priming and restrains effector
      differentiation.
AB  - A promising strategy in tumor immunotherapy is the use of activated dendritic
      cells as vehicles for tumor vaccines with the goal of activating anti-tumor T
      cell responses. Current formulations for dendritic cell-based immunotherapies
      have limited effects on patient survival, providing motivation for further
      investigation of ways to enhance dendritic cell priming of anti-tumor T cell
      responses. Using a brief in vitro priming model, we have found that B7-H1
      expressed by activated dendritic cells is integrated during priming of naive
      CD8(+) T cells and functions to limit the differentiation of effector T cell
      responses. CD8(+) T cells primed by B7-H1-deficient dendritic cells exhibit
      increased production of IFN-gamma, enhanced target cell killing, and improved
      anti-tumor activity. Additionally, enhanced memory populations arise from CD8(+)
      T cells primed by B7-H1-deficient dendritic cells. Based on these findings, we
      suggest that early blockade of B7-H1 signaling should be investigated as a
      strategy to improve dendritic cell-based anti-tumor immunotherapy. 

PMID- 24893860
TI  - Description of Taphrina antarctica f.a. sp. nov., a new anamorphic ascomycetous
      yeast species associated with Antarctic endolithic microbial communities and
      transfer of four Lalaria species in the genus Taphrina.
AB  - In the framework of a large-scale rock sampling in Continental Antarctica, a
      number of yeasts have been isolated. Two strains that are unable to grow above 20
      degrees C and that have low ITS sequence similarities with available data in the
      public domain were found. The D1/D2 LSU molecular phylogeny placed them in an
      isolated position in the genus Taphrina, supporting their affiliation to a not
      yet described species. Because the new species is able to grow in its anamorphic
      state only, the species Taphrina antarctica f.a. (forma asexualis) sp. nov. has
      been proposed to accommodate both strains (type strain DBVPG 5268(T), DSM
      27485(T) and CBS 13532(T)). Lalaria and Taphrina species are dimorphic
      ascomycetes, where the anamorphic yeast represents the saprotrophic state and the
      teleomorph is the parasitic counterpart on plants. This is the first record for
      this genus in Antarctica; since plants are absent on the continent, we
      hypothesize that the fungus may have focused on the saprotrophic part of its life
      cycle to overcome the absence of its natural host and adapt environmental
      constrains. Following the new International Code of Nomenclature for Algae, Fungi
      and Plants (Melbourne Code 2011) the reorganization of Taphrina-Lalaria species
      in the teleomorphic genus Taphrina is proposed. We emend the diagnosis of the
      genus Taphrina to accommodate asexual saprobic states of these fungi. Taphrina
      antarctica was registered in MycoBank under MB 808028.

PMID- 24893859
TI  - Bioactive compounds or metabolites from black raspberries modulate T lymphocyte
      proliferation, myeloid cell differentiation and Jak/STAT signaling.
AB  - Bioactive phytochemicals from natural products, such as black raspberries (BRB;
      Rubus occidentalis), have direct anticancer properties on malignant cells in
      culture and in xenograft models. BRB components inhibit cancer progression in
      more complex rodent carcinogenesis models. Although mechanistic targets for BRB
      phytochemicals in cancer cells are beginning to emerge, the potential role in
      modulating host immune processes impacting cancer have not been systematically
      examined. We hypothesized that BRB contain compounds capable of eliciting potent
      immunomodulatory properties that impact cellular mediators relevant to chronic
      inflammation and tumor progression. We studied both an ethanol extract from black
      raspberries (BRB-E) containing a diverse mixture of phytochemicals and two
      abundant phytochemical metabolites of BRB produced upon ingestion (Cyanidin-3
      Rutinoside, C3R; Quercitin-3-Rutinoside, Q3R). BRB-E inhibited proliferation, and
      viability of CD3/CD28 activated human CD4(+) and CD8(+) T lymphocytes. BRB-E also
      limited in vitro expansion of myeloid-derived suppressor cells (MDSC) and their
      suppressive capacity. Pre-treatment of immune cells with BRB-E attenuated IL-6
      mediated phosphorylation of signal transducer and activator of transcription-3
      (STAT3) and IL-2-induced STAT5 phosphorylation. In contrast, pre-treatment of
      immune cells with the C3R and Q3R metabolites inhibited MDSC expansion, IL-6
      mediated STAT3 signaling, but not IL-2-induced STAT5 phosphorylation and were
      less potent inhibitors of T cell viability. Together these data indicate that BRB
      extracts and their physiologically relevant metabolites contain phytochemicals
      that affect immune processes relevant to carcinogenesis and immunotherapy.
      Furthermore, specific BRB components and their metabolites may be a source of
      lead compounds for drug development that exhibits targeted immunological outcomes
      or inhibition of specific STAT-regulated signaling pathways. 

PMID- 24893861
TI  - Enhanced bioactivity of polyvinylidene chloride films using argon ion bombardment
      for guided bone regeneration.
AB  - Polyvinylidene chloride (PVDC) is a long chain carbon synthetic polymer. The
      objective of this study was to improve the bioactivity of PVDC films through
      surface modification using argon (Ar) ion bombardment to create Ar-modified PVDC
      films (Ar-PVDC) to address the clinical problems of guided bone regeneration
      (GBR), which is technique-sensitive, and low bone regenerative ability. First,
      the effects of Ar ion bombardment, a low temperature plasma etching technique
      widely used in industry, on PVDC film wettability, surface chemistry, and
      morphology were confirmed. Next, fibroblast-like and osteoblast-like cell
      attachment and proliferation on Ar-PVDC were assessed. As a preclinical in vivo
      study, Ar-PVDC was used to cover a critical-sized bone defect on rat calvaria and
      osteoconductivity was evaluated by micro-computed tomography analysis and
      histological examinations. We found that the contact angle of PVDC film decreased
      by 50 degrees  because of the production of -OH groups on the PVDC film surface,
      though surface morphological was unchanged at 30 min after Ar ion bombardment. We
      demonstrated that cell attachment increased by about 40% and proliferation by
      more than 140% because of increased wettability, and 2.4 times greater bone
      regeneration was observed at week 3 with Ar-PVDC compared with untreated PVDC
      films. These results suggest that Ar ion bombardment modification of PVDC
      surfaces improves osteoconductivity, indicating its potential to increase bone
      deposition during GBR.

PMID- 24893862
TI  - Longitudinal associations among change in overweight status, fear of negative
      evaluation, and weight-related teasing among obese adolescents.
AB  - OBJECTIVE: To examine longitudinal bidirectional associations between changes in
      adolescents' weight status and psychosocial constructs. METHOD: 118 obese
      adolescents aged 13-16 years participated in a behavioral weight control
      intervention. Percent overweight (OW), fear of negative evaluation (FNE), and
      frequency of weight-related teasing (WRT) were collected at baseline, end of
      intervention, and 12 and 24 months post-randomization. 3 multivariate latent
      change score models were estimated to examine longitudinal cross-lagged
      associations between: (1) OW and FNE; (2) OW and WRT; and (3) FNE and WRT.
      RESULTS: Decreases in OW were prospectively associated with subsequent decreases
      in both FNE and WRT; however, changes in FNE and WRT were not prospectively
      associated with subsequent change in OW. Decreases in FNE were prospectively
      associated with subsequent decreases in WRT. CONCLUSION: Moderate weight loss in
      the context of a behavioral weight control intervention has positive long-term
      implications for obese adolescents' peer relations.

PMID- 24893863
TI  - Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes
      less than 6 years of age in the United States T1D Exchange and German/Austrian
      DPV registries.
AB  - AIMS/HYPOTHESIS: The study aimed to compare participant characteristics,
      treatment modalities and clinical outcomes in registry participants less than 6
      years old. METHODS: Participant characteristics, treatment modalities and
      clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis
      [DKA]) as well as frequencies of attaining HbA1c goals in line with the
      International Society for Pediatric and Adolescent Diabetes (<7.5% [<58
      mmol/mol]) and ADA (<8.5% [<69 mmol/mol]) were compared. RESULTS: Insulin pump
      use was more frequent (74% vs 50%, p < 0.001) and HbA1c levels lower in the
      Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX)
      (mean 7.4% vs 8.2%, p < 0.001). A lower HbA1c level was seen in the DPV compared
      with the T1DX for both pump users (p < 0.001) and injection users (p < 0.001).
      More children from DPV were meeting the recommended HbA1c goals, compared with
      children from T1DX (HbA1c <7.5%: 56% vs 22%, p < 0.001; HbA1c <8.5%: 90% vs 66%,
      p < 0.001). The adjusted odds of having an HbA1c level <7.5% or <8.5% were 4.2 (p
      < 0.001) and 3.6 (p < 0.001) higher for the DPV than the T1DX, respectively. The
      frequency of SH did not differ between registries or by HbA1c, whereas the
      frequency of DKA was higher for the T1DX and greater in those with higher HbA1c
      levels. CONCLUSIONS/INTERPRETATION: DPV data indicate that an HbA1c of <7.5% can
      frequently be achieved in children with type 1 diabetes who are under 6 years
      old. An improved metabolic control of type 1 diabetes in young patients appears
      to decrease the risk of DKA without increasing SH. The greater frequency of
      suboptimal control in young patients in the T1DX compared with the DPV is not
      fully explained by a less frequent use of insulin pumps and may relate to the
      higher HbA1c targets that are recommended for this age group in the USA.

PMID- 24893865
TI  - Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and
      Vascular Endstage Disease (PREVEND) study.
AB  - AIMS/HYPOTHESIS: Oxidative stress plays a key role in the development of type 2
      diabetes mellitus. We previously showed that the circulating antioxidant
      peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed
      to evaluate the association of Prx4 with type 2 diabetes risk in the general
      population. METHODS: We analysed data on 7,972 individuals from the Prevention of
      Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28-75 years)
      with no diabetes at baseline. Logistic regression models adjusted for age, sex,
      smoking, waist circumference, hypertension and family history of diabetes were
      used to estimate the ORs for type 2 diabetes. RESULTS: During a median follow up
      of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The
      median (Q1-Q3) Prx4 level was 0.84 (0.53-1.40) U/l in individuals who developed
      type 2 diabetes and 0.68 (0.43-1.08) U/l in individuals who did not develop type
      2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type
      2 diabetes was 1.16 (1.05-1.29) in the whole population; by sex, it was 1.31
      (1.14-1.50) for men and 1.03 (0.87-1.21) for women. Further adjustment for other
      clinical measures did not materially change the results. The addition of Prx4 to
      a validated diabetes risk score significantly improved the prediction of type 2
      diabetes in men (p = 0.002 for reclassification improvement).
      CONCLUSIONS/INTERPRETATION: Our findings suggest that elevated serum Prx4 levels
      are associated with a higher risk of incident type 2 diabetes. For men, taking
      Prx4 into consideration can improve type 2 diabetes prediction over a validated
      diabetes risk score; in contrast, there is no improvement in risk prediction for
      women.

PMID- 24893866
TI  - A rare case of pituitary tuberculoma-diagnosed and managed conservatively.

PMID- 24893864
TI  - Type 2 diabetes-related genetic risk scores associated with variations in fasting
      plasma glucose and development of impaired glucose homeostasis in the prospective
      DESIR study.
AB  - AIMS/HYPOTHESIS: Genome-wide association studies have firmly established 65
      independent European-derived loci associated with type 2 diabetes and 36 loci
      contributing to variations in fasting plasma glucose (FPG). Using individual data
      from the Data from an Epidemiological Study on the Insulin Resistance Syndrome
      (DESIR) prospective study, we evaluated the contribution of three genetic risk
      scores (GRS) to variations in metabolic traits, and to the incidence and
      prevalence of impaired fasting glycaemia (IFG) and type 2 diabetes. METHODS:
      Three GRS (GRS-1, 65 type 2 diabetes-associated single nucleotide polymorphisms
      [SNPs]; GRS-2, GRS-1 combined with 24 FPG-raising SNPs; and GRS-3, FPG-raising
      SNPs alone) were analysed in 4,075 DESIR study participants. GRS-mediated effects
      on longitudinal variations in quantitative traits were assessed in 3,927
      nondiabetic individuals using multivariate linear mixed models, and on the
      incidence and prevalence of hyperglycaemia at 9 years using Cox and logistic
      regression models. The contribution of each GRS to risk prediction was evaluated
      using the C-statistic and net reclassification improvement (NRI) analysis.
      RESULTS: The two most inclusive GRS were significantly associated with increased
      FPG (beta = 0.0011 mmol/l per year per risk allele, p GRS-1  = 8.2 * 10(-5) and p
      GRS-2  = 6.0 * 10(-6)), increased incidence of IFG and type 2 diabetes (per
      allele: HR GRS-1 1.03, p = 4.3 * 10(-9) and HR GRS-2 1.04, p = 1.0 * 10(-16)),
      and the 9 year prevalence (OR GRS-1 1.13 [95% CI 1.10, 1.17], p = 1.9 * 10(-14)
      for type 2 diabetes only; OR GRS-2 1.07 [95% CI 1.05, 1.08], p = 7.8 * 10(-25),
      for IFG and type 2 diabetes). No significant interaction was found between GRS-1
      or GRS-2 and potential confounding factors. Each GRS yielded a modest, but
      significant, improvement in overall reclassification rates (NRI GRS-1 17.3%, p =
      6.6 * 10(-7); NRI GRS-2 17.6%, p = 4.2 * 10(-7); NRI GRS-3 13.1%, p = 1.7 * 10(
      4)). CONCLUSIONS/INTERPRETATION: Polygenic scores based on combined genetic
      information from type 2 diabetes risk and FPG variation contribute to
      discriminating middle-aged individuals at risk of developing type 2 diabetes in a
      general population.

PMID- 24893867
TI  - Adjunct coronary endarterectomy increases myocardial infarction and early
      mortality after coronary artery bypass grafting: a meta-analysis.
AB  - Coronary endarterectomy (CE) may provide a useful adjunct to coronary artery
      bypass grafting (CABG) in patients with extensive, diffuse coronary atheroma.
      However, concerns regarding its morbidity and mortality have created uncertainty
      as to the role of CE in the current era. The aim of this study was therefore to
      quantitatively summarize the short- and long-term outcomes of CE. Twenty
      observational studies were identified by systematic literature search,
      incorporating 54 440 patients (7366 CABG + CE; 47 074 CABG only), which were
      analysed using random-effects modelling. Heterogeneity, subgroup analysis,
      quality scoring and risk of bias were assessed. Primary end-points were 30-day
      mortality and perioperative and postoperative myocardial infarction (MI).
      Secondary end-points were postoperative morbidity, intensive care unit (ITU)
      stay, hospital stay and long-term graft patency. Adjunctive CE significantly
      increased 30-day mortality [odds ratios (OR) = 1.69, 95% confidence interval (CI)
      [1.49-1.92], P <0.00001], perioperative (OR = 2.10, 95% CI [1.82-2.43], P
      <0.00001) and postoperative MI (OR = 3.34, 95% CI [1.74-6.41], P = 0.0003) when
      compared with CABG alone. Furthermore, postoperative ventricular arrhythmias,
      pulmonary complications, renal failure and inotrope use were significantly
      greater in patients undergoing adjunct CE. CE also increased ITU and hospital
      stay and reduced angiographic patency at the last follow-up (OR = 0.57, 95% CI
      [0.36-0.88]). Increased 30-day morbidity and mortality continues to raise
      concerns over the safety of adjunct CE. Furthermore, the procedure can be
      associated with worse long-term graft patency. To better determine whether CE
      should remain a viable adjunct to CABG, novel studies must focus on collecting
      prospective data with homogeneous inclusion criteria for CE as well as isolating
      outcomes for different coronary vessels and standardizing postoperative
      anticoagulation. 

PMID- 24893868
TI  - The early and long-term outcomes of completion pneumonectomy: report of 56 cases.
AB  - OBJECTIVES: The aim of this study was to analyse the early and long-term results
      of completion pneumonectomy (CP). METHODS: A retrospective review of consecutive
      patients who underwent CP in the Shanghai Chest Hospital. RESULTS: Fifty-six CP
      were performed between January 2003 and July 2013. There were 45 conventional CP
      (CCP) and 11 rescue CP (RCP) cases. CCP was defined as resection of the remaining
      lung because of the occurrence of new lesions in patients with previous lung
      resection. RCP was defined as resection of the remaining lung because of severe
      complication after primary lung surgery. The mortality and morbidity rates of CCP
      were 4.4 and 33.3%, respectively. For CCP, the morbidity was significantly higher
      in benign cases than in malignant cases (80.0 vs 27.5%, P = 0.04). The mortality
      and morbidity rates of RCP were 27.3 and 90.9%, respectively. For RCP, advanced
      age (P = 0.046) and preoperative mechanical ventilation (P = 0.03) were related
      to higher postoperative mortality. The overall 5-year survival rate was 80% for
      benign cases, whereas for lung malignancy cases, it was 30%. Survival varied
      (median 60.0 vs 35.0 vs 10.0 months, I vs II vs III, P < 0.01) for different TNM
      stages and was better for a time interval (between primary surgery and occurrence
      of lesion) of >2 years (median 60.0 vs 18.0 months, P < 0.01). CONCLUSIONS: CP
      was an operation with high risk, especially for RCP. Advanced age and mechanical
      ventilation before the operation were related to higher mortality in RCP. CCP of
      benign cases was related to higher postoperative risk, but with good survival.
      For lung malignancy, survival was better for a time interval (between primary
      surgery and occurrence of lesion) of >2 years.

PMID- 24893869
TI  - Effect of oral tamoxifen on the healing of corrosive oesophageal burns in an
      experimental rat model.
AB  - OBJECTIVES: Corrosive oesophagitis is a common health problem in children. Scar
      tissue can develop during the recovery period, and as a result, serious narrowing
      of the oesophagus can develop, in turn causing morbidity and mortality. In
      previous studies, it was argued that tamoxifen (TAM) may have antifibrotic
      effects beyond its oestrogen antagonist or agonist properties. We aimed to
      examine the possible effects of TAM on fibrosis and stricture formation, which
      are complications of corrosive oesophagitis. METHODS: Three study groups were
      formed as follows: a non-oesophageal burn group (NON-EB, n = 6), an oesophageal
      burn group (EB, n = 6) and an oesophageal burn + tamoxifen group (EB-TAM, n = 6).
      In the NON-EB rats, the oesophageal lumen was washed with 0.9% NaCl while, in the
      EB and EB-TAM rats, the distal oesophagus was burned with a 50% NaOH solution.
      After application of this solution to the EB-TAM group rats, 0.4 mg/kg/day of TAM
      was administered via gavage for 7 days. Twenty-two days later, the rat oesophagi
      were examined histopathologically for inflammation, granulation, collagen
      deposition and stenosis. RESULTS: In the EB group rats, the inflammation,
      collagen deposition and stenosis scores increased compared with those of the
      other groups. In the EB-TAM group, these three scores were lower compared with
      those of the EB group rats, but higher compared with those of the NON-EB group
      rats. No significant difference was observed in the granulation scores between
      the EB and EB-TAM groups. It was also observed that the EB-TAM group rats gained
      more weight than those in the EB group. CONCLUSIONS: According to the data
      obtained, TAM use prevents inflammation, collagenization and stricture
      development. TAM may be a useful medicine in the treatment of corrosive
      oesophagitis.

PMID- 24893870
TI  - Optimal bypass graft design for left anterior descending and diagonal territory
      in multivessel coronary disease.
AB  - OBJECTIVES: Coronary artery bypass grafting for multivessel disease requires an
      appropriate graft design to avoid the competition of flow between the graft and
      the native vessel in order to achieve a sufficient coronary flow and durable
      graft patency. METHODS: Three-dimensional computational models of the left
      coronary artery were created based on the angiographic data. Three stenosis
      patterns of 75 and 90% combinations were created in the left anterior descending
      artery (LAD), the diagonal branch (Dx) and the circumflex artery (LCx). The left
      internal thoracic artery (LITA) was anastomosed to the LAD, and separate
      saphenous vein grafts (SVGs) were anastomosed to the Dx and the LCx in the
      'Independent' model. The 'Sequential' model included sequential SVG anastomoses
      to the Dx and the LCx with a left internal thoracic artery-left anterior
      descending artery bypass, and Y-composite arterial grafts to LAD and Dx were
      created in the 'Composite' model. RESULTS: The 'Independent' model had high
      reverse flow from the Dx to the LAD in systole, resulting in decreased LITA flow
      when Dx stenosis was mild. The 'Sequential' model also had reverse flow in
      diastole, resulting in additional LAD flow. The 'Composite' model distributed
      increased flow to the Dx when Dx stenosis was severe, resulting in decreased flow
      to the LAD. CONCLUSIONS: Systematic flow evaluation is beneficial for determining
      the optimal bypass graft arrangement in patients with multivessel disease.
      Individual SVG anastomoses to the Dx and the LCx are not desirable when Dx
      stenosis is not severe and a Y-composite arterial graft to the LAD and the Dx is
      not desirable when Dx stenosis is severe.

PMID- 24893872
TI  - Usefulness of vessel-sealing devices for <=7 mm diameter vessels: a randomized
      controlled trial for human thoracoscopic lobectomy in primary lung cancer.
AB  - OBJECTIVES: Vessel-sealing devices (VSDs) are widely used for various surgical
      procedures, including thoracoscopic surgery, but very few reports have compared
      their safety and usefulness with human thoracoscopic lobectomy procedures not
      employing VSDs. METHODS: Primary lung cancer patients for whom a thoracoscopic
      lobectomy involving mediastinal lymph node dissection was planned in our
      department from April 2011 to March 2013 were recruited for the study. Patients
      were randomly allocated to a control group (n = 14) or a VSD group (n = 44),
      which comprised three sub-groups, namely EnSeal (n = 17), LigaSure (n = 15) and
      Harmonic (n = 12). The control group comprised patients undergoing surgery solely
      with ligation and conventional electrocautery. EnSeal, LigaSure and Harmonic were
      chosen because they are the three most popular disposable VSDs used in Japan. In
      the VSD groups, the proximal side of pulmonary artery stumps (<=7 mm diameter)
      were ligated and then treated with respective devices. Primary end-points were
      burst pressure of the pulmonary artery stump (measured using resected specimens),
      operative time, intraoperative blood loss, instances of endostapler use,
      intraoperative surgeon stress (assessed by visual analogue scale) and
      postoperative drainage volume and duration. As a secondary objective, the
      individual VSD groups were also compared with each other. RESULTS: The burst
      pressure of ligation-treated pulmonary artery stumps was higher than that of VSD
      treated stumps (P <0.0001). The burst pressure of <5-mm-wide VSD-treated stumps
      was higher than that of >=5-mm-wide stumps (P = 0.0421). However, the burst
      pressure for all groups and all vessel diameters was sufficient to withstand the
      physiological pulmonary artery pressure. The VSD group demonstrated reduced
      intraoperative blood loss (P = 0.0241), surgeon stress (P = 0.0002),
      postoperative drainage volume (P = 0.0358) and shortened postoperative drainage
      duration (P = 0.0449). Operative time and the instances of endostapler use did
      not significantly differ. Comparison between each of the VSD groups revealed no
      significant differences. None of the patients experienced serious perioperative
      complications or died because of surgery. CONCLUSION: VSD is simple and safe to
      use in thoracoscopic lobectomy involving mediastinal lymph node dissection for
      primary lung cancer. Furthermore, none of the VSDs used in this study presented
      any observable differences in quality that could lead to clinical problems.

PMID- 24893871
TI  - Transcatheter aortic valve implantation of a second-generation valve for pure
      aortic regurgitation: procedural outcome, haemodynamic data and follow-up.
AB  - OBJECTIVES: The second-generation Jenavalve prosthesis (Jenavalve Technology,
      Inc., Munich, Germany) is the first transcatheter valve Conformite Europeene (CE)
      marked for treatment of both aortic stenosis (AS) and pure aortic regurgitation
      (AR). Although the feasibility of the Jenavalve transcatheter aortic valve
      implantation (TAVI) in patients with pure AR has been described, haemodynamic and
      follow-up data are lacking. METHODS: We report on a series of 10 transapical
      Jenavalve implantations for pure AR between December 2012 and September 2013. The
      patients were determined for TAVI by heart team decision at high surgical risk
      [log EuroSCORE (European System for Cardiac Operative Risk Evaluation) >20%],
      frailty or Charlson Comorbidity Index (CCI). Transaortic gradients and right
      heart haemodynamics were measured invasively before and after TAVI.
      Ventriculography and transoesophageal echocardiography were used to determine
      paravalvular regurgitation. All-cause mortality, NYHA functional class and
      echocardiographic measurements were followed up at 30 days and at 3, 9 and 12
      months postoperatively. RESULTS: Overall, mean age was 79 +/- 9 years, mean left
      ventricular ejection fraction 50 +/- 17% and mean log EuroSCORE 28.3 +/- 17.1%.
      There were no perioperative complications. Paravalvular regurgitation immediately
      after implantation was graded none (n = 6), trace (n = 3) or mild (n = 1).
      Overall 30-day mortality was 30% (3/10). Three patients refused further
      treatment, such as haemodialysis or treatment of mitral regurgitation. Rate for
      pacemaker implantation was 2/10 (20%). CONCLUSIONS: Intraprocedural success and
      haemodynamic data in our cases were good. The mortality in our group highlighted
      the importance of careful patient selection, especially for this pathology. The
      Jenavalve prosthesis proved to be suitable for treatment of AR in surgical high
      risk patients.

PMID- 24893873
TI  - Development of a composite and vascularized tracheal scaffold in the omentum for
      in situ tissue engineering: a canine model.
AB  - OBJECTIVES: We herein report on development of a composite (synthetic and
      biological) tracheal scaffold with vascularized autologous connective tissue in
      the omentum, followed by in situ tissue engineering of the composite scaffold
      with the pedicled omentum. In this preliminary report, we focus on development
      and evaluation of the vascularized autologous connective tissue in the omentum.
      METHODS: In animal experiment 1, a polypropylene framework as a synthetic
      component was placed in the omental sac for 3 weeks and another was placed in the
      pouch of Douglas as a control in five beagle dogs. In animal experiment 2, a
      polypropylene framework placed in the omental sac for 3 weeks was compared with a
      polypropylene framework coated with porcine atelocollagen, which was also placed
      in the omental sac in another five dogs, to investigate whether the coating of
      porcine atelocollagen contributes to development of more vascularized connective
      tissue. Macroscopic, radiological and histological evaluations were performed for
      developed autologous connective tissue on the frameworks, with a focus on its
      thickness and capillary vessels. RESULTS: In animal experiment 1, the
      polypropylene framework in the omentum developed a composite tracheal scaffold
      with homogeneous and significantly thicker (2.6 +/- 0.5 vs 1.2 +/- 0.4 mm, P
      <0.0001) connective tissue in which more capillary vessels per 10-power field of
      view (3.5 +/- 2.2 vs 0 +/- 0, P = 0.015) were identified, compared with the
      control in the pouch of Douglas. In animal experiment 2, the omentum developed
      significantly thicker connective tissue on the polypropylene framework coated
      with porcine atelocollagen (3.6 +/- 0.7 vs 2.2 +/- 0.4 mm, P <0.0001) in which
      not significantly more capillary vessels were identified (3.5 +/- 2.2 vs 5.0 +/-
      2.7, P = 0.12), compared with the framework that was not coated. CONCLUSIONS:
      Placement of the polypropylene framework in the omental sac resulted in
      development of homogeneous and vascularized autologous connective tissue on the
      polypropylene framework for a composite tracheal scaffold. The framework coated
      with porcine atelocollagen did not show an additional benefit in inducing
      vascularization. This preliminary report will be followed by the long-term
      evaluations of in situ tissue engineering of the composite tracheal scaffold.

PMID- 24893874
TI  - Impact of coronary collateral circulation and severity of coronary artery disease
      in the development of postoperative atrial fibrillation.
AB  - OBJECTIVES: Atrial fibrillation (AF) after cardiac surgery has been reported to
      be approximately 30%, making it one of the most important causes of morbidity and
      mortality post surgery. Although various clinical and laboratory predictors and
      underlying mechanisms progressing to postoperative AF have been proposed, the
      role of ischaemia in pathogenesis is doubtful. In this study, the association of
      coronary collateral circulation (CCC) and severity of coronary artery disease
      (CAD) with the development of postoperative AF was investigated. METHODS: A total
      of 597 patients who underwent on-pump coronary artery bypass surgery were
      included in the study. Pre-, peri- and postoperative variables were recorded in a
      computerized database. CCC and severity of CAD were documented for each patient
      according to Rentrop classification and Gensini score. RESULTS: Postoperative AF
      was observed in 96 patients (16.1%). Advanced age, female gender, presence of
      hypertension and low haematocrit level were significantly associated with
      postoperative AF. By contrast, CCC and severity of CAD were not associated with
      postoperative AF (P = 0.22 and 0.5, respectively). Older age and lower
      preoperative haematocrit levels were the major predictors of postoperative AF
      development in the multivariate regression analysis. CONCLUSIONS: CCC and
      severity of CAD did not have a significant effect on the occurrence of
      postoperative AF, suggesting an ineffective role of myocardial ischaemia in the
      development of this condition.

PMID- 24893875
TI  - Identification of reference genes for RT-qPCR in ovine mammary tissue during late
      pregnancy and lactation and in response to maternal nutritional programming.
AB  - The mammary gland is a complex tissue consisting of multiple cell types which,
      over the lifetime of an animal, go through repeated cycles of development
      associated with pregnancy, lactation and involution. The mammary gland is also
      known to be sensitive to maternal programming by environmental stimuli such as
      nutrition. The molecular basis of these adaptations is of significant interest,
      but requires robust methods to measure gene expression. Reverse-transcription
      quantitative PCR (RT-qPCR) is commonly used to measure gene expression, and is
      currently the method of choice for validating genome-wide expression studies. RT
      qPCR requires the selection of reference genes that are stably expressed over
      physiological states and treatments. In this study we identify suitable reference
      genes to normalize RT-qPCR data for the ovine mammary gland in two physiological
      states; late pregnancy and lactation. Biopsies were collected from offspring of
      ewes that had been subjected to different nutritional paradigms during pregnancy
      to examine effects of maternal programming on the mammary gland of the offspring.
      We evaluated eight candidate reference genes and found that two reference genes
      (PRPF3 and CUL1) are required for normalising RT-qPCR data from pooled RNA
      samples, but five reference genes are required for analyzing gene expression in
      individual animals (SENP2, EIF6, MRPL39, ATP1A1, CUL1). Using these stable
      reference genes, we showed that TET1, a key regulator of DNA methylation, is
      responsive to maternal programming and physiological state. The identification of
      these novel reference genes will be of utility to future studies of gene
      expression in the ovine mammary gland. 

PMID- 24893877
TI  - The complete mitochondrial genome of snubnose pompano Trachinotus blochii
      (Teleostei, Carangidae).
AB  - The complete mitochondrial genome of Trachinotus blochii was determined using the
      polymerase chain reaction. The complete mitochondrial DNA sequence is 16,558 bp
      in length. It consists of 13 protein-coding genes, 22 transfer RNA genes, two
      rRNA genes and two non-coding regions. Overall base composition of its
      mitochondrial genome is estimated to be 29.21% for A, 15.74% for G, 26.49% for T,
      28.56% for C, respectively, with a high A + T content (55.70%). The control
      region contains three conserved sequence blocks, a termination-associated
      sequence and a TATA box. The complete mitochondrial genome sequence of T. blochii
      can provide a basic data for the studies on population structure, molecular
      systematic, stock evaluation and conservation genetics. It is also helpful to
      develop the rational management strategies for T. blochii resource.

PMID- 24893876
TI  - Oxidative stress modulates the expression of genes involved in cell survival in
      DeltaF508 cystic fibrosis airway epithelial cells.
AB  - Although cystic fibrosis (CF) pathophysiology is explained by a defect in CF
      transmembrane conductance regulator (CFTR) protein, the broad spectrum of disease
      severity is the consequence of environmental and genetic factors. Among them,
      oxidative stress has been demonstrated to play an important role in the evolution
      of this disease, with susceptibility to oxidative damage, decline of pulmonary
      function, and impaired lung antioxidant defense. Although oxidative stress has
      been implicated in the regulation of inflammation, its molecular outcomes in CF
      cells remain to be evaluated. To address the question, we compared the gene
      expression profile in NuLi-1 cells with wild-type CFTR and CuFi-1 cells
      homozygous for DeltaF508 mutation cultured at air-liquid interface. We analyzed
      the transcriptomic response of these cell lines with microarray technology, under
      basal culture conditions and after 24 h oxidative stress induced by 15 MUM 2,3
      dimethoxy-1,4-naphtoquinone. In the absence of oxidative conditions, CuFi-1 gene
      profiling showed typical dysregulated inflammatory responses compared with NuLi
      1. In the presence of oxidative conditions, the transcriptome of CuFi-1 cells
      reflected apoptotic transcript modulation. These results were confirmed in the
      CFBE41o- and corrCFBE41o- cell lines as well as in primary culture of human CF
      airway epithelial cells. Altogether, our data point to the influence of oxidative
      stress on cell survival functions in CF and identify several genes that could be
      implicated in the inflammation response observed in CF patients. 

PMID- 24893878
TI  - Complete mitochondrial genome of the wild eri silkworm, Samia canningi
      (Lepidoptera: Saturniidae).
AB  - The saturniid silkworm species of the genus Samia are potential silk producing
      insects. Thus, Samia canningi (Lepidoptera: Saturniidae) is a potential candidate
      to introduce for silk production. The complete mitochondrial genome of S.
      canningi was 15,384 bp long that contained 37 genes along with a control region.
      The arrangement of the PCGs was same as the majority of Lepidoptera, presenting
      the order, trnM/trnI/trnQ between nad2 and control region. Twelve of 13 PCGs
      started with ATN codons, but cox2 with GTG, which is often found in insects.
      Genes overlapped in a total of 29 bp, 221 bp of intergenic spacer sequences was
      found in seventeen regions and the longest 54 bp one was found between trnQ and
      nad2 as typical in Lepidoptera. In lrRNA, the 21-bp long, tandemly duplicated
      repeat was characteristically found (TAAAATTATTTATAATATAAA) between 13,663 and
      13,706. AT rich region has the motif "ATAGA" and 18 bp poly T stretch, typically
      conserved in Lepidoptera. 

PMID- 24893879
TI  - Efficient development of highly polymorphic microsatellite markers based on
      polymorphic repeats in transcriptome sequences of multiple individuals.
AB  - The first hurdle in developing microsatellite markers, cloning, has been overcome
      by next-generation sequencing. The second hurdle is testing to differentiate
      polymorphic from nonpolymorphic loci. The third hurdle, somewhat hidden, is that
      only polymorphic markers with a large effective number of alleles are
      sufficiently informative to be deployed in multiple studies. Both steps are
      laborious and still performed manually. We have developed a strategy in which we
      first screen reads from multiple genotypes for repeats that show the most length
      variants, and only these are subsequently developed into markers. We validated
      our strategy in tetraploid garden rose using Illumina paired-end transcriptome
      sequences of 11 roses. Of 48 tested two markers failed to amplify, but all others
      were polymorphic. Ten loci amplified more than one locus, indicating duplicated
      genes or gene families. Completely avoiding duplicated loci will be difficult
      because the range of numbers of predicted alleles of highly polymorphic single-
      and multilocus markers largely overlapped. Of the remainder, half were replicate
      markers (i.e. multiple primer pairs for one locus), indicating the difficulty of
      correctly filtering short reads containing repeat sequences. We subsequently
      refined the approach to eliminate multiple primer sets to the same loci. The
      remaining 18 markers were all highly polymorphic, amplifying on average 11.7
      alleles per marker (range = 6-20) in 11 tetraploid roses, exceeding the 8.2
      alleles per marker of the 24 most polymorphic markers genotyped previously. This
      strategy therefore represents a major step forward in the development of highly
      polymorphic microsatellite markers. 

PMID- 24893881
TI  - Fluorescence turn-on detection of gaseous nitric oxide using ferric
      dithiocarbamate complex functionalized quantum dots.
AB  - Functional quantum dots (QDs) grafted with ferric dithiocarbamate complex layers
      (QDs-Fe(III)(DTC)3) were fabricated and demonstrated to be selectively reactive
      to nitric oxide. The dithiocarbamate (DTC) was covalently conjugated to the amine
      coated QDs by a condensation reaction of the carboxyl in DTC and the amino
      polymer in surface of QDs. The weak fluorescence of QDs-Fe(III)(DTC)3 was
      attributed to the energy transfer between CdSe/ZnS and Fe(III)(DTC)3 complex at
      the surface of the functionalized quantum dots. Nitric oxide could greatly switch
      on the fluorescence of QDs-Fe(III)(DTC)3 by displacing the DTC in the
      Fe(III)(DTC)3 accompanied by reducing Fe(III) to Fe(II), thus shutting off the
      energy transfer way. The limit of detection for nitric oxide was estimated to be
      3.3 MUM and the specific detection was not interfered with other reactive oxygen
      species. Moreover, the probe was demonstrated for the sensing of gaseous nitric
      oxide, and the visual detection limit was as low as 10 ppm, showing the potential
      for sensing nitric oxide by the naked eye. 

PMID- 24893880
TI  - Carbonic anhydrase 9 is associated with chemosensitivity and prognosis in breast
      cancer patients treated with taxane and anthracycline.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is one of the standard care regimens
      for patients with resectable early-stage breast cancer. It would be advantageous
      to determine the chemosensitivity of tumors before initiating NAC. One of the
      parameters potentially compromising such chemosensitivity would be a hypoxic
      microenvironment of cancer cells. The aim of this study was thus to clarify the
      correlation between expression of the hypoxic marker carbonic anhydrase-9 (CA9)
      and chemosensitivity to NAC as well as prognosis of breast cancer patients.
      METHODS: A total of 102 patients with resectable early-stage breast cancer was
      treated with NAC consisting of FEC (5-fluorouracil, epirubicin, and
      cyclophosphamide) followed by weekly paclitaxel before surgery. Core needle
      biopsy (CNB) specimens and resected tumors were obtained from all patients before
      and after NAC, respectively. Chemosensitivity to NAC and the prognostic potential
      of CA9 expression were evaluated by immunohistochemistry. RESULTS: CA9 positivity
      was detected in the CNB specimens from 47 (46%) of 102 patients. The CA9
      expression in CNB specimens was significantly correlated with pathological
      response, lymph node metastasis, and lymph-vascular invasion. Multivariate
      analysis revealed that the CA9 expression in CNB specimens was an independent
      predictive factor for pathological response. The Kaplan-Meier survival curve
      revealed a significant negative correlation (p=0.013) between the disease-free
      survival (DFS) and the CA 9 expression in resected tissues after NAC.
      Multivariate regression analyses indicated that the CA9 expression in resected
      tissues was an independent prognostic factor for DFS. CONCLUSIONS: CA9 expression
      in CNB specimens is a useful marker for predicting chemosensitivity, and CA9
      expression in resected tissue is prognostic of DFS in patients with resectable
      early-stage breast cancer treated by sequential FEC and weekly paclitaxel prior
      to resection.

PMID- 24893882
TI  - Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-oxidation
      pathway.
AB  - CYP24A1 is the multicatalytic cytochrome P450 responsible for the catabolism of
      vitamin D via the C23- and C24-oxidation pathways. We successfully expressed the
      labile human enzyme in Escherichia coli and partially purified it in an active
      state that permitted detailed characterization of its metabolism of 1,25
      dihydroxyvitamin D3 [1,25(OH)2 D3] and the intermediates of the C24-oxidation
      pathway in a phospholipid-vesicle reconstituted system. The C24-oxidation pathway
      intermediates, 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, 24
      oxo-1,23,25-trihydroxyvitamin D3 and tetranor-1,23-dihydroxyvitamin D3, were
      enzymatically produced from 1,25(OH)2 D3 using rat CYP24A1. Both 1,25(OH)2 D3 and
      1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 were found to partition strongly
      into the phospholipid bilayer when in aqueous medium. Changes to the phospholipid
      concentration did not affect the kinetic parameters for the metabolism of
      1,25(OH)2 D3 by CYP24A1, indicating that it is the concentration of substrates in
      the membrane phase (mol substrate.mol phospholipid(-1) ) that determines their
      rate of metabolism. CYP24A1 exhibited Km values for the different C24
      intermediates ranging from 0.34 to 15 mmol.mol phospholipid(-1) , with 24-oxo
      1,23,25-trihydroxyvitamin D3 [24-oxo-1,23,25(OH)3 D3] displaying the lowest and
      1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3 D3] displaying the highest. The kcat
      values varied by up to 3.8-fold, with 1,24,25(OH)3 D3 displaying the highest kcat
      (34 min(-1) ) and 24-oxo-1,23,25(OH)3 D3 the lowest. The data show that the
      cleavage of the side chain of 24-oxo-1,23,25(OH)3 D3 occurs with the highest
      catalytic efficiency (kcat /Km ) and produces 1-hydroxy-23-oxo-24,25,26,27
      tetranorvitamin D3 and not 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, as the
      primary product. These kinetic analyses also show that intermediates of the C24
      oxidation pathway effectively compete with precursor substrates for binding to
      the active site of the enzyme, which manifests as an accumulation of
      intermediates, indicating that they dissociate after each catalytic step. 

PMID- 24893883
TI  - The effect of marginal bone level changes on the stability of dental implants in
      a short-term evaluation.
AB  - OBJECTIVES: To evaluate whether changes in marginal bone level (MBL) around
      implants, in sites with different bone types, affect the over time implant
      stability measured by resonance frequency analysis (RFA). MATERIAL AND METHODS:
      Seventy-eight implants were inserted into jawbones of 32 patients using a two
      stage surgical protocol, and implant bone sites were grouped according to the
      Lekholm and Zarb bone classification. The implant stability quotient (ISQ) was
      measured by RFA at four time points: implant placement, uncovering,
      rehabilitation, and at 1-year follow-up after loading. The MBL was measured on
      periapical radiographs at uncovering and at 1-year follow-up. Percent change in
      bone level was calculated based on the difference between the implant length and
      height from the crestal bone level to the implant apex. Descriptive statistics,
      Pearson's correlation, and repeated-measures ANOVA were used for data analysis.
      RESULTS: Significant improvement of ISQ was found between implant insertion and
      uncovering surgery (P < 0.001), while no significant changes were detected
      throughout the remaining follow-up period. The greatest improvement of ISQ was
      observed for bone type 4, compared with the other groups (P < 0.001). Percent
      change in bone level had no effect on longitudinal measures of ISQ (P = 0.337).
      The ISQ difference between uncovering and 1 year after loading was not correlated
      with percent change in bone level (r = 0.16; P = 0.157). CONCLUSION: There was
      increased implant stability after implant placement, but it was not affected by
      changes in marginal bone level during the first year of loading.

PMID- 24893884
TI  - Insecure attachment behavior and partner violence: incorporating couple
      perceptions of insecure attachment and relational aggression.
AB  - Intimate partner violence and insecure attachment are therapeutically relevant
      concepts when working with couples. The link between attachment and intimate
      partner violence has been examined in the literature, but an area of aggression
      that often goes unexamined is relational aggression, or using third parties as a
      means of being aggressive toward a partner. We asked how participants' attachment
      behaviors were related to their own and partners' relational and physical
      aggression. We used structural equation modeling to estimate actor-partner
      interdependence among these relationships in 644 heterosexual couples. Results
      indicated significant partner paths from attachment to relational aggression, as
      well as significant actor paths between relational aggression and physical
      aggression. Implications were discussed. Data for this study were collected from
      the RELATE assessment. 

PMID- 24893885
TI  - An online daily diary study of alcohol use using Amazon's Mechanical Turk.
AB  - INTRODUCTION AND AIMS: In recent years, unprecedented levels of Internet access
      and the widespread growth of emergent communication technologies have resulted in
      significantly greater population access for substance use researchers. Despite
      the research potential of such technologies, the use of the Internet to recruit
      individuals for participation in event-level research has been limited. The
      purpose of this paper is to provide a brief account of the methods and results
      from an online daily diary study of alcohol use. DESIGN AND METHODS: Participants
      were recruited using Amazon's Mechanical Turk. Eligible participants completed a
      brief screener assessing demographics and health behaviours, with a subset of
      individuals subsequently recruited to participate in a 2 week daily diary study
      of alcohol use. RESULTS: Multilevel models of the daily alcohol data derived from
      the Mechanical Turk sample (n = 369) replicated several findings commonly
      reported in daily diary studies of alcohol use. DISCUSSION AND CONCLUSIONS:
      Results demonstrate that online participant recruitment and survey administration
      can be a fruitful method for conducting daily diary alcohol research.

PMID- 24893887
TI  - Influence of interpregnancy interval on birth timing.
AB  - OBJECTIVE: To assess the influence of inadequate birth spacing on birth timing
      distribution across gestation. DESIGN: Population-based retrospective cohort
      study using vital statistics birth records. SETTING: Ohio, USA. STUDY POPULATION:
      Singleton, non-anomalous live births >=20 weeks to multiparous mothers, 2006
      2011. METHODS: Birth frequency at each gestational week was compared following
      short IPIs of <6, 6-12 and 12-18 months versus referent group, normal IPI>=18
      months. MAIN OUTCOME MEASURES: Frequency of birth at each gestational week;
      preterm <37 weeks; <39 and >=40 weeks. RESULTS: Of 454,716 births, 87% followed a
      normal IPI>=18 months, 10.7% had IPI 12-18 months and 2.2% with IPI<12 months.
      The risk of delivery<39 weeks was higher following short IPI<12 months, adj OR
      (odds ratio) 2.78 (95% CI 2.64, 2.93). 53.3% of women delivered before the 39th
      week after IPI<12 months compared with 37.5% of women with normal IPI, P<0.001.
      Likewise, birth at >=40 weeks was decreased (16.9%) following short IPI<12 months
      compared to normal IPI, 23.2%, adj OR 0.67 (95% CI 0.64, 0.71). This resulted in
      a shift of the frequency distribution curve of birth by week of gestation to the
      left for pregnancies following a short IPI<12 months and 12-18 months compared
      to, birth spacing>=18 months. CONCLUSIONS: While short IPI is a known risk factor
      for preterm birth, our data show that inadequate birth spacing is associated with
      decreased gestational age for all births. Pregnancies following short IPIs have a
      higher frequency of birth at all weeks of gestation prior to 39 and fewer
      births>=40 weeks, resulting in overall shortened pregnancy duration.

PMID- 24893888
TI  - Application of PhiSP-1 and PhiSP-3 as a therapeutic strategy against Salmonella
      Enteritidis infection using Caenorhabditis elegans as model organism.
AB  - The potential of Salmonella-specific phages PhiSP-1 and PhiSP-3 as biocontrol
      agents was studied in vitro, employing host cell lysis test and in vivo, using
      Caenorhabditis elegans as a model organism. For in vivo testing, stage 4 C.
      elegans larvae were experimentally infected with the pathogen Salmonella. Worm
      mortality was scored for 10 days. TD50 (the time required for 50% of the
      nematodes to die) of infected worms in the presence of bacteriophages was
      comparable to uninfected worms, and the two phages provided an increased
      protection than each one. This study in addition demonstrated the simplicity,
      elegance, and the cost effectiveness of the C. elegans model for in vivo
      validation.

PMID- 24893886
TI  - The normal and pathologic roles of the Alzheimer's beta-secretase, BACE1.
AB  - As the most common neurodegenerative disease, therapeutic avenues for the
      treatment and prevention of Alzheimer's Disease are highly sought after. The
      aspartic protease BACE1 is the initiator enzyme for the formation of Abeta, a
      major constituent of amyloid plaques that represent one of the hallmark
      pathological features of this disorder. Thus, targeting BACE1 for disease
      modifying AD therapies represents a rationale approach. The collective knowledge
      acquired from investigations of BACE1 deletion mutants and characterization of
      BACE1 substrates has downstream significance not only for the discovery of AD
      drug therapies but also for predicting side effects of BACE1 inhibition. Here we
      discuss the identification and validation of BACE1 as the beta-secretase
      implicated in AD, in addition to information regarding BACE1 cell biology,
      localization, substrates and potential physiological functions derived from BACE1
      knockout models. 

PMID- 24893889
TI  - Exploratory study of sleeping patterns in children admitted to hospital.
AB  - AIMS: Sleep is considered an important time of healing and restoration during
      illness. The primary aim of this study was to determine the prevalence of self
      reported sleep disturbance in children admitted to a tertiary children's hospital
      with a variety of medical diagnoses. METHODS: Parents of children admitted to the
      hospital, aged between 1 and 18 years, were asked to complete a sleep diary
      during one night of their child's hospital stay. Children older than 12 years
      were asked to complete a diary independently. Descriptive statistics were used to
      summarise the data. RESULTS: Overall, 107 children were surveyed for one hospital
      inpatient night. The overall prevalence of poor sleep was 52.3%. The wide age
      range and variety of diagnosis limited further detailed analysis of specific
      causes of this problem. Poor sleep prior to admission was the strongest predictor
      of poor sleep in hospital suggesting that these children already had an
      underlying sleep problem. Unprompted awakenings were predominantly due to
      toileting (17.8%) or were spontaneous (17.8%). Factors specific to the hospital
      environment that woke children were nursing cares (25.2%), alarms (12.1%) and
      pain (12.1%). CONCLUSIONS: Children admitted to hospital have a higher prevalence
      of poor sleep compared with healthy children in the community. Children were
      woken frequently by both external noise and attention provided by hospital staff.
      Education of hospital staff about the importance of sleep for children and
      factors that affect children's sleep may reduce the negative impact of
      hospitalisation on children's sleep.

PMID- 24893892
TI  - Outcome of behavioural treatment for idiopathic chronic constipation.
AB  - BACKGROUND/AIM: Behavioural therapy is effective in patients with chronic
      intractable constipation despite standard treatment, but long-term results in
      unselected patients are unclear. This study investigates the effects of
      behavioural therapy on symptoms, subjective well-being, and the physical and
      mental quality of life. METHODS: Patients who had failed standard care for
      idiopathic chronic constipation underwent behavioural therapy in a specialist
      clinic. Symptom severity and quality of life were assessed before and after
      therapy using the 'Constipation Scoring System' and the Short-Form 36
      questionnaire. The primary outcome was subjective perception of improvement.
      Secondary outcomes were symptoms of constipation and quality of life scores.
      RESULTS: Of 233 consecutive patients with self-reported constipation (median
      symptom duration 5-10 years, median age 44 years, females 86%), 180 (77%)
      completed treatment in a median of three (range 1-7) sessions. One hundred and
      sixty-five patients (71% of all referrals or 92% of those completing treatment)
      reported subjective improvement. Median bowel frequency improved from once every
      2-7 days to 1-3 per day (P = 0.05). Pain and bloating improved in more than 80%
      of patients. The Short-Form 36 physical (P < 0.05) and mental (P < 0.05)
      composite scores improved significantly. Patients with a longer duration of
      symptoms were less likely to complete treatment. Digital evacuation prior to
      treatment was a predictor of poor outcome. CONCLUSION: Behavioural therapy is
      associated with significant improvement in symptoms of chronic constipation and
      quality of life. Non-drug therapies that successfully treat patients with
      functional gut disorders resistant to standard treatment are needed in the
      mainstream provision of care.

PMID- 24893890
TI  - EGFR variant heterogeneity in glioblastoma resolved through single-nucleus
      sequencing.
AB  - Glioblastomas (GBM) with EGFR amplification represent approximately 50% of newly
      diagnosed cases, and recent studies have revealed frequent coexistence of
      multiple EGFR aberrations within the same tumor, which has implications for
      mutation cooperation and treatment resistance. However, bulk tumor sequencing
      studies cannot resolve the patterns of how the multiple EGFR aberrations coexist
      with other mutations within single tumor cells. Here, we applied a population
      based single-cell whole-genome sequencing methodology to characterize genomic
      heterogeneity in EGFR-amplified glioblastomas. Our analysis effectively
      identified clonal events, including a novel translocation of a super enhancer to
      the TERT promoter, as well as subclonal LOH and multiple EGFR mutational variants
      within tumors. Correlating the EGFR mutations onto the cellular hierarchy
      revealed that EGFR truncation variants (EGFRvII and EGFR carboxyl-terminal
      deletions) identified in the bulk tumor segregate into nonoverlapping subclonal
      populations. In vitro and in vivo functional studies show that EGFRvII is
      oncogenic and sensitive to EGFR inhibitors currently in clinical trials. Thus,
      the association between diverse activating mutations in EGFR and other subclonal
      mutations within a single tumor supports an intrinsic mechanism for proliferative
      and clonal diversification with broad implications in resistance to treatment.
      SIGNIFICANCE: We developed a novel single-cell sequencing methodology capable of
      identifying unique, nonoverlapping subclonal alterations from archived frozen
      clinical specimens. Using GBM as an example, we validated our method to
      successfully define tumor cell subpopulations containing distinct genetic and
      treatment resistance profiles and potentially mutually cooperative combinations
      of alterations in EGFR and other genes.

PMID- 24893893
TI  - Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: case report and
      literature review.
AB  - Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an
      extremely rare neoplasm characterized by morphological analogy to papillary
      thyroid carcinoma and abnormal expression of thyroid transcription factor-1 (TTF
      1). Here we report a novel case of TL-LGNPPA with literature review. The patient
      was a 43-year-old woman complaining of nasal obstruction. Laryngoscopic study and
      computed tomography identified a pedunculated mass located on the posterior edge
      of the left nasal septum. Histologically, the tumor consisted of papillary growth
      of cuboidal or columnar epithelium. Tubular architecture and a spindle cell
      component were also observed focally. Some tumor cells exhibited intra-nuclear
      cytoplasmic inclusions. Immunohistochemically, the neoplastic cells were positive
      for pancytokeratin (AE1/AE3), CK7, CK19, TTF-1, vimentin and HBME1, but negative
      for thyroglobulin, Pax8 and CK5/6. Ki67-labeling index reached 5% in the most
      concentrated spot. Despite the morphological and immunohistochemical similarity
      to papillary thyroid carcinoma, no BRAF V600E mutation was detected by mutation
      specific immunohistochemistry. The patient had neither local recurrence nor
      distant metastasis 19 months after removal of the tumor. 

PMID- 24893894
TI  - Success of sequential free flaps in head and neck reconstruction.
AB  - BACKGROUND: The need for additional free flaps following an initial free flap
      reconstruction sometimes arises. However, there is understandable hesitation to
      perform subsequent free flaps due to concerns regarding recipient vessel
      availability, flap loss, and other complications. METHODS: An analysis of
      patients undergoing one or more sequential head and neck free flap
      reconstructions between 2000 and 2012 was performed. RESULTS: Two hundred seventy
      three free flaps were performed on 117 patients over the course of 2, 3, or 4
      surgeries, with 23 patients receiving 2 or 3 simultaneous free flaps in a single
      surgery. The success rate of subsequent free flaps was 98.7% compared to 99.1%
      for initial free flaps in the same patients (p = 1.00). The complication rate
      following subsequent free flaps was 42.9% compared to 36.8% following initial
      free flaps (p = 0.46). Flap success rates for double/triple simultaneous free
      flaps were 97.8% compared to 99.1% for single flaps (p = 0.41) and the
      complication rate for double/triple simultaneous free flaps was 34.6% compared to
      47.8% for single flaps (p = 0.20). In patients receiving oral or pharyngeal
      sequential free flap reconstructions, 90.1% demonstrated at least 80% speech
      intelligibility and 81.6% remained feeding tube-independent. The 5-year survival
      of patients undergoing sequential free flaps was 75.4%. CONCLUSIONS: Multiple
      sequential free flaps are feasible and reliable in appropriately selected
      patients. These findings suggest that the ability to perform free flap
      reconstruction should rarely limit a patient's candidacy for resection of
      recurrent cancers or consideration for surgery intended to improve patient
      aesthetics or function.

PMID- 24893891
TI  - AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR
      inhibitors in lung cancer.
AB  - First-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provide significant
      clinical benefit in patients with advanced EGFR-mutant (EGFRm(+)) non-small cell
      lung cancer (NSCLC). Patients ultimately develop disease progression, often
      driven by acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is
      a novel oral, potent, and selective third-generation irreversible inhibitor of
      both EGFRm(+) sensitizing and T790M resistance mutants that spares wild-type
      EGFR. This mono-anilino-pyrimidine compound is structurally distinct from other
      third-generation EGFR TKIs and offers a pharmacologically differentiated profile
      from earlier generation EGFR TKIs. Preclinically, the drug potently inhibits
      signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+)
      mutant cell lines in vitro, with lower activity against wild-type EGFR lines,
      translating into profound and sustained tumor regression in EGFR-mutant tumor
      xenograft and transgenic models. The treatment of 2 patients with advanced
      EGFRm(+) T790M(+) NSCLC is described as proof of principle. SIGNIFICANCE: We
      report the development of a novel structurally distinct third-generation EGFR
      TKI, AZD9291, that irreversibly and selectively targets both sensitizing and
      resistant T790M(+) mutant EGFR while harboring less activity toward wild-type
      EGFR. AZD9291 is showing promising responses in a phase I trial even at the first
      dose level, with first published clinical proof-of-principle validation being
      presented.

PMID- 24893895
TI  - Rates of skin flap necrosis are increased in fat diabetic rats as compared to
      normal rat controls.

PMID- 24893896
TI  - Successful lower extremity salvage with free flap after endovascular angioplasty
      in peripheral arterial occlusive disease.
AB  - OBJECTIVE: Most patients with peripheral arterial occlusive disease undergo lower
      limb amputation due to complex wounds on their lower extremities. We have taken
      the challenging approach of combining angioplasty and free tissue transfer for
      limb salvage. METHODS: Between October 2011 and December 2013, 11 patients
      (average age of 56.8 years; ranged from 43-72 years old) with peripheral arterial
      occlusive disease of main tibioperoneal arteries underwent preoperative
      angioplasty. Afterward, free tissue transfers (nine anterolateral thigh free
      flaps, one vastus lateralis muscle free flap, and one deep femoral artery
      perforator flap) were performed on these patients for lower extremity salvage and
      reconstruction. RESULTS: All 11 free tissue transfers after angioplasty were
      successful without operative mortality or major complications. Minimal wound
      dehiscence was seen in one case, and partial flap necrosis was seen in the other
      cases. During the follow-up period, all of the patients had their wounds healed
      completely and achieved acceptable contour and quality of gait. CONCLUSION: The
      preoperative angioplasty provides well-vascularized tissue that both controls
      infection and helps free flaps to survive. Therefore, the patients due to receive
      leg amputation in spite of the free tissue transfer can achieve limb salvage by
      using the additional technique of angioplasty. This combined approach was
      successful in preserving the functional aspects along with the aesthetic results
      for the lower limb reconstruction.

PMID- 24893897
TI  - The evolution of internal mammary vessel preparation in microsurgical breast
      reconstruction: what is the current evidence?

PMID- 24893898
TI  - Letter: a comparison of short-term surgical outcomes between NHS and private
      sector abdominoplasty surgery.

PMID- 24893899
TI  - Non-crushing intestinal clamps used as a tourniquet for resection of a large
      vascular malformation at the lower lip.

PMID- 24893900
TI  - Bowel obstruction following DIEP-flap breast reconstruction: an unexpected
      complication.

PMID- 24893901
TI  - Therapeutic strategies in multiple sclerosis: a focus on neuroprotection and
      repair and relevance to schizophrenia.
AB  - Multiple sclerosis is the leading nontraumatic cause of neurologic disability in
      young adults. The need to prevent neurodegeneration and promote repair in
      multiple sclerosis (MS) has gained increasing interest in the last decade leading
      to the search and development of pharmacological agents and non-pharmacologic
      strategies able to target not only the inflammatory but also the
      neurodegenerative component of the disease. This paper will provide an overview
      of the therapeutics currently employed in MS, with a focus on their potential
      neuroprotective effects and on the MRI methods employed to detect and monitor in
      vivo neuroprotection and repair and the relevance of this information to
      schizophrenia investigation and treatment.

PMID- 24893902
TI  - Hippocampal and parahippocampal cortex volume predicts recollection in
      schizophrenia.

PMID- 24893903
TI  - Cognitive remediation for individuals with psychosis in a supported education
      setting: a randomized controlled trial.
AB  - Cognitive remediation (CR) has demonstrated good outcomes when paired with
      supported employment, however little is known about its effectiveness when
      integrated into a supported education program. This randomized controlled trial
      examined the effectiveness of integrating CR within a supported education program
      compared with supported education without CR. Thirty-seven students with
      psychosis were recruited into the study in the 2012 academic year. Academic
      functioning, cognition, self-esteem, and symptomatology were assessed at
      baseline, at 4months following the first academic term in which CR was provided,
      and at 8months assessing maintenance of gains. The treatment group demonstrated
      better retention in the academic program and a trend of improvement across a
      range of academic functional domains. While both treatment and control groups
      showed improvement in cognitive measures, the outcomes were not augmented by CR
      training. CR was also associated with significant and sustained improvements in
      self esteem. Further research, investigating specific intervention components is
      required to clarify the mixed findings regarding the effectiveness of CR in an
      education setting. 

PMID- 24893904
TI  - Suicide in first episode psychosis: a nationwide cohort study.
AB  - BACKGROUND: Relatively little is known about suicide in diagnostic subtypes of
      first episode psychosis (FEP). Our aim was to assess suicide rates and potential
      risk factors for suicide in FEP. METHODS: This is a national register-based
      cohort study of patients born in 1973-1978 in Sweden and who were hospitalized
      with a FEP between ages 15 and 30years (n=2819). The patients were followed from
      date of discharge until death, emigration, or 31st of December 2008. The suicide
      rates for six diagnostic subtypes of FEP were calculated. Suicide incidence rate
      ratios (IRRs) were calculated to evaluate the association between suicide and
      psychiatric, familial, social, and demographic factors. RESULTS: In total 121
      patients died by suicide. The overall suicide rate was 4.3 (95% confidence
      interval [CI] 3.5-5.0) per 1000person-years. The highest suicide rates were found
      in depressive disorder with psychotic symptoms and in delusional disorder. In an
      adjusted model, the strongest risk factors for suicide were self-harm (IRR 2.7,
      CI 1.7-4.4) or a conviction for violent crime (IRR 2.0, CI 1.3-3.2). Also having
      a first-degree relative with a schizophrenia/bipolar diagnosis (IRR 2.1, CI 1.2
      3.6) or substance use disorder (IRR 2.0, CI 1.2-3.2) were significant risk
      factors for suicide. CONCLUSIONS: Impulsive behavior such as self-harm as well as
      having a family history of severe mental disorder or substance use are important
      risk factors for suicide in FEP.

PMID- 24893905
TI  - Do schizophrenia patients with low P50-suppression report more perceptual
      anomalies with the sensory gating inventory?
AB  - BACKGROUND: P50 amplitude changes in dual click conditioning-testing procedure
      might be a neurophysiological marker of deficient sensory gating in
      schizophrenia. However, the relationship between abnormalities in the
      neurophysiological and phenomenological dimensions of sensory gating in
      schizophrenia remains unclear. The aim of the present study was to determine if
      patients with low P50-suppression (below 50%) report more perceptual anomalies.
      METHODS: Three groups were compared: twenty-nine schizophrenia patients with high
      P50-suppression (above 50% amplitude suppression), twenty-three schizophrenia
      patients with low P50-suppression (below 50%) and twenty-six healthy subjects.
      The Sensory Gating Inventory (SGI), a four-factor self-report questionnaire, was
      used to measure perceptual anomalies related to sensory gating. A comparison of
      demographic and clinical data was also carried out. RESULTS: Patients with low
      P50-suppression presented: i) significantly higher scores on the SGI (for the
      overall SGI score and for each of the 4 factors) and ii) significantly larger P50
      amplitude at the second click, than both patients with high P50-suppression and
      healthy subjects. There were no group differences in the most of demographic and
      clinical data. DISCUSSION: The finding offers support for conceptual models
      wherein abnormal neurophysiologic responses to repetitive stimuli give rise to
      clinically relevant perceptions of being inundated and overwhelmed by external
      sensory stimuli. Further studies are needed to explore the contributions of
      clinical symptoms, medication and neuropsychological functions to the
      relationship between P50-suppression and the SGI, and the role of sensory "gating
      in" versus "gating out".

PMID- 24893907
TI  - An fMRI study of visual lexical decision in patients with schizophrenia and
      clinical high-risk individuals.
AB  - Disturbances in semantic and phonological aspects of language processing are
      indicated in patients with schizophrenia, and in high-risk individuals for
      schizophrenia. To uncover neural correlates of the disturbances, a previous
      functional magnetic resonance imaging (fMRI) study using a visual lexical
      decision task in block design reported less leftward lateralization in the
      inferior frontal cortices, in patients with schizophrenia and individuals with
      high genetic risk for psychosis compared with normal control subjects. However,
      to our knowledge, no previous study has investigated contrasts between word and
      non-word processing that allow dissociation between semantic and phonological
      processing using event-related design visual lexical decision fMRI tasks in
      subjects with ultra-high-risk for psychosis (UHR) and patients with
      schizophrenia. In the current study, 20 patients with schizophrenia, 11 UHR, and
      20 demographically matched controls underwent lexical decision fMRI tasks.
      Compared with controls, both schizophrenia and UHR groups showed significantly
      decreased activity in response to non-words compared with words in the inferior
      frontal regions. Additionally, decreased leftward lateralization in the non-word
      compared with word activity contrast was found in subjects with UHR compared with
      controls, which was not evident in patients with schizophrenia. The present
      findings suggest neural correlates of difficulty in phonological aspects of
      language processing during non-word processing in contrast to word, which at
      least partially commonly underlies the pathophysiology of schizophrenia and UHR.
      Together with a previous study in genetic high-risk subjects, the current results
      also suggest that reduced functional lateralization in the language-related
      frontal cortex may be a vulnerability marker for schizophrenia. Furthermore, the
      current result may suggest that the genetic basis of psychosis is presumed to be
      related to the evolution of the language capacity characteristic of humans. 

PMID- 24893906
TI  - Genetic underpinnings of white matter 'connectivity': heritability, risk, and
      heterogeneity in schizophrenia.
AB  - Schizophrenia is a highly heritable disorder. Thus, the combination of genetics
      and brain imaging may be a useful strategy to investigate the effects of risk
      genes on anatomical connectivity, and for gene discovery, i.e. discovering the
      genetic correlates of white matter phenotypes. Following a database search, I
      review evidence for heritability of white matter phenotypes. I also review
      candidate gene investigations, examining association of putative risk variants
      with white matter phenotypes, as well as the recent flurry of research exploring
      relationships of genome-wide significant risk loci with white matter phenotypes.
      Finally, I review multivariate and polygene approaches, which constitute a new
      wave of imaging-genetics research, including large collaborative initiatives
      aiming to discover new genes that may predict aspects of white matter
      microstructure. The literature supports the heritability of white matter
      phenotypes. Loci in genes intimately implicated in oligodendrocyte and myelin
      development, growth and maintenance, and neurotrophic systems are associated with
      white matter microstructure. GWAS variants have not yet sufficiently been
      explored using DTI-based evaluation of white matter to draw conclusions, although
      micro-RNA 137 is promising due to its potential regulation of other GWAS
      schizophrenia genes. Many imaging-genetic studies only include healthy
      participants, which, while helping control for certain confounds, cannot address
      questions related to disease heterogeneity or symptom expression, and thus more
      studies should include participants with schizophrenia. With sufficiently large
      sample sizes, the future of this field lies in polygene strategies aimed at risk
      prediction and heterogeneity dissection of schizophrenia that can translate to
      personalized interventions.

PMID- 24893909
TI  - A selective review of structural connectivity abnormalities of schizophrenic
      patients at different stages of the disease.
AB  - Schizophrenia has long been hypothesized to result from a disconnection syndrome
      due to a disruption of the association fibers of the brain. However, only with
      the advent of in vivo neuroimaging, a formal disconnectivity hypothesis for
      schizophrenia has been developed. Diffusion tensor MRI, a non-invasive technique
      which is sensitive to features of tissue microstructure and to the anatomy of the
      white matter fibers, has gained a crucial role in the field. Here, we provide a
      state-of-the-art review of structural connectivity abnormalities detected in
      schizophrenia and discuss the most relevant findings at preclinical, first
      episode drug-naive, and chronic stages. Imaging studies showed white matter
      alterations from the preclinical to the chronic stage of the disease, which
      involve the corticospinal tracts, interhemispheric connections, long association
      white matter tracts, cerebello-thalamo-cortical circuit, and limbic system. Such
      abnormalities were found to be associated with the psychiatric and cognitive
      manifestations of the disease and to predict, at least partially, the patient
      clinical evolution and response to treatment.

PMID- 24893908
TI  - White matter development in the early stages of psychosis.
AB  - Schizophrenia has been conceptualized as a disorder of both neurodevelopment and
      a disorder of connectivity. One important aspect of the neurodevelopmental
      hypothesis is that schizophrenia is no longer thought to have discrete illness
      time points, but rather a long trajectory of brain changes, spanning many years,
      across a series of stages of the disease including the prodrome, first episode,
      and chronic period. As the disease progresses, there is a complex relationship
      between age related changes and disease related changes. Therefore, neural
      changes, and specifically white matter based connectivity changes, in
      schizophrenia may be best conceptualized based on a lifespan trajectory. In this
      selective review, we discuss healthy changes in white matter integrity that occur
      with age, as well as changes that occur across illness stages. We further propose
      a set of models that might explain lifespan changes in white matter integrity in
      schizophrenia, with the conclusion that the evidence most strongly supports a
      pattern of disrupted maturation during adolescence, with the potential for later
      changes that may be a result of disease neurotoxicity, abnormal or excessive
      aging effects, as well as medication, cohort or other effects. Thus, when
      considering white matter integrity in psychosis, it is critical to consider age
      in addition to other contributing factors including disease specific effects.
      Discovery of the factors driving healthy white matter development across the
      lifespan and deviations from the normal developmental trajectory may provide
      insights relevant to the discovery of early treatment interventions. 

PMID- 24893910
TI  - Effect of antipsychotic drugs on gene expression in the prefrontal cortex and
      nucleus accumbens in the spontaneously hypertensive rat (SHR).
AB  - Antipsychotic drugs (APDs) are the standard treatment for schizophrenia. The
      therapeutic effect of these drugs is dependent upon the dopaminergic D2 blockade,
      but they also modulate other neurotransmitter pathways. The exact mechanisms
      underlying the clinical response to APDs are not fully understood. In this study,
      we compared three groups of animals for the expression of 84 neurotransmitter
      genes in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Each group was
      treated with a different APD (risperidone, clozapine or haloperidol), and with a
      non-treated group of spontaneously hypertensive rats (SHRs), which is an animal
      model for schizophrenia. This study also explored whether or not differential
      expression was regulated by DNA methylation in the promoter region (PR). In the
      clozapine group, we found that Chrng was downregulated in the NAcc and six genes
      were downregulated in the PFC. In the haloperidol group, Brs3 and Glra1 were
      downregulated, as was Drd2 in the clozapine group and Drd3, Galr3 and Gabrr1 in
      the clozapine and haloperidol groups. We also encountered four hypermethylated CG
      sites in the Glra1 PR, as well as three in the risperidone group and another in
      the haloperidol group, when compared to non-treated rats. Following the APD
      treatment, the gene expression results revealed the involvement of genes that had
      not previously been described, in addition to the activity of established genes.
      The investigation of the involvement of these novel genes can lead to better
      understanding about the specific mechanisms of action of the individual APDs
      studied. 

PMID- 24893912
TI  - A prospective, randomized, single - blind study comparing intraplaque injection
      of thiocolchicine and verapamil in Peyronie's Disease: a pilot study.
AB  - OBJECTIVES: To compare the response to tiocolchicine and verapamil injection in
      the plaque of patients with Peyronie's disease. MATERIALS AND METHODS:
      Prospective, single-blind, randomized study, selecting patients who have
      presented Peyronie's disease for less than 18 months. Thiocolchicine 4mg or
      verapamil 5mg were given in 7 injections (once a week). Patients who had received
      any treatment for Peyronie's disease in the past three months were excluded. The
      parameters used were the International Index of Erectile Function (IIEF-5) score,
      analysis of the curvature on pharmaco-induced erections and size of the plaque by
      ultrasonography. RESULTS: Twenty-five patients were randomized, 13 received
      thiocolchicine and 12 were treated with verapamil. Both groups were statistically
      similar. The mean curvature was 46.7o and 36.2o before and after thiocolchicine,
      respectively (p=0.019) and 50.4o and 42.08o before and after verapamil,
      respectively (p=0.012). The curvature improved in 69% of patients treated with
      thiocolchicine and in 66% of those who received verapamil. Regarding sexual
      function, there was an increase in the IIEF-5 from 16.69 to 20.85 (p=0.23) in the
      thiocolchicine group. In the verapamil group the IIEF-5 score dropped from 17.50
      to 16.25 (p=0.58). In the thiocolchicine group, the plaque was reduced in 61% of
      patients. In the verapamil group, 8% presented decreased plaque size. No adverse
      event was associated to thiocolchicine. CONCLUSION: The use of thiocolchicine in
      Peyronie's disease demonstrated improvement on penile curvature and reduction in
      plaque size. Thiocolchicine presented similar results to verapamil in curvature
      assessment. No significant side effects were observed with the use of
      tiocolchicine.

PMID- 24893911
TI  - Financial literacy is associated with medial brain region functional connectivity
      in old age.
AB  - Financial literacy refers to the ability to access and utilize financial
      information in ways that promote better outcomes. In old age, financial literacy
      has been associated with a wide range of positive characteristics; however, the
      neural correlates remain unclear. Recent work has suggested greater co-activity
      between anterior-posterior medial brain regions is associated with better brain
      functioning. We hypothesized financial literacy would be associated with this
      pattern. We assessed whole-brain functional connectivity to a posterior cingulate
      cortex (PCC) seed region of interest (ROI) in 138 participants of the Rush Memory
      and Aging Project. Results revealed financial literacy was associated with
      greater functional connectivity between the PCC and three regions: the right
      ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right
      precuneus. Results also revealed financial literacy was associated negatively
      with functional connectivity between the PCC and left caudate. Post hoc analyses
      showed the PCC-vmPFC relationship accounted for the most variance in a regression
      model adjusted for all four significant functional connectivity relationships,
      demographic factors, and global cognition. These findings provide information on
      the neural mechanisms associated with financial literacy in old age. 

PMID- 24893913
TI  - Myiasis associated with penile carcinoma: a new trend in developing countries?
AB  - OBJECTIVES: The aim of this study is to report an unusual form of penile cancer
      presentation associated with myiasis infestation, treatment options and outcomes.
      MATERIALS AND METHODS: We studied 10 patients with suspected malignant neoplasm
      of the penis associated with genital myiasis infestation. Diagnostic assessment
      was conducted through clinical history, physical examination, penile biopsy,
      larvae identification and computerized tomography scan of the chest, abdomen and
      pelvis. Clinical and pathological staging was done according to 2002 TNM
      classification system. Radical inguinal lymphadenectomy was conducted according
      to the primary penile tumor pathology and clinical lymph nodes status. RESULTS:
      Patients age ranged from 41 to 77 years (mean=62.4). All patients presented
      squamous cell carcinoma of the penis in association with myiasis infestation
      caused by Psychoda albipennis. Tumor size ranged from 4cm to 12cm (mean=5.3).
      Circumcision was conducted in 1 (10%) patient, while penile partial penectomy was
      performed in 5 (50%). Total penectomy was conducted in 2 (20%) patients, while
      emasculation was the treatment option for 2 (20%). All patients underwent radical
      inguinal lymphadenectomy. Prophylactic lymphadenectomy was performed on 3 (30%)
      patients, therapeutic on 5 (50%), and palliative lymphadenectomy on 2 (20%)
      patients. Time elapsed from primary tumor treatment to radical inguinal
      lymphadenectomy was 2 to 6 weeks. The mean follow-up was 34.3 months. CONCLUSION:
      The occurrence of myiasis in the genitalia is more common in patients with
      precarious hygienic practices and low socio-economic level. The treatment option
      varied according to the primary tumor presentation and clinical lymph node
      status.

PMID- 24893914
TI  - Potential therapeutic strategies for non - muscle invasive bladder cancer based
      on association of intravesical immunotherapy with p - mapa and systemic
      administration of cisplatin and doxorubicin.
AB  - The present study describes the histopathological and molecular effects of P-MAPA
      (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride)
      intravesical immunotherapy combined with systemic doxorubicin or cisplatin for
      treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal
      model. Our results showed an undifferentiated tumor, characterizing a tumor
      invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in
      situ (pTa) in the Cancer group. The histopathological changes were similar
      between the combined treatment with intravesical P-MAPA plus systemic Cisplatin
      and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions
      progression and histopathological recovery in 80% of the animals. The animals
      treated systemically with cisplatin or doxorubicin singly, showed 100% of
      malignant lesions in the urinary bladder. Furthemore, the combined treatment with
      P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions
      progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and
      VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic
      cisplatin and in intravesical P-MAPA alone treatments than other groups. In
      contrast, PTEN protein levels were significantly higher in intravesical P-MAPA
      plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it
      could be concluded that combination of intravesical P-MAPA immunotherapy and
      systemic cisplatin in the NMIBC animal model was effective, well tolerated and
      showed no apparent signs of antagonism between the drugs. In addition,
      intravesical P-MAPA immunotherapy may be considered as a valuable option for
      treatment of BCG unresponsive patients that unmet the criteria for early
      cystectomy.

PMID- 24893915
TI  - Prognostic features for quality of life after radical cystectomy and orthotopic
      neobladder.
AB  - PURPOSE: To analyse prognostic features on quality of life (QoL) following
      radical cystectomy and urinary diversion via orthotopic neobladder in a single
      centre patient cohort. MATERIALS AND METHODS: Postoperative QoL of 152 patients
      was assessed retrospectively using the validated QLQ-C30 questionnaire. Potential
      associations of patient's quality of life including pre-and intraoperative
      characteristics, surgeon experience, postoperative time course, adjuvant
      therapies, and functional outcome were defined a priori and evaluated. Mann
      Whitney-U-, Kruskal-Wallis-, Spearman correlation and post hoctesting were used.
      A multivariate analysis using a multiple logistic regression model was performed.
      A p value <0.05 was considered to be statistically significant. RESULTS: Median
      follow-up was 48 months. Univariate analysis of prognostic features for health
      related QoL revealed a significant impact of gender (p=0.019), performance status
      (p<0.001), experience of surgeon (>100 previous cystectomies, p=0.007), and nerve
      sparing surgery (p=0.001). Patients who underwent secondary chemotherapy or
      radiotherapy had significant lower QLQ-C30 scores (p=0.04, p=0.02 respectively).
      Patients who were asymptomatic had a significantly higher quality of life
      (p<0.001). A significant impact of severity of incontinence based on ICIQ-SF
      score (p<0.001) and daily pad usage (p<0.001), existence of daytime incontinence
      (p<0.001), existence of urgency symptoms (p=0.007), and IIEF-5 score (p<0.001)
      could be observed. In multivariate analysis, independent prognostic relevance
      could be confirmed for preoperative ECOG performance status of 0 (p=0.020 vs.
      ECOG 1, p=0.047 vs. ECOG 2), experience of the respective surgeon (>=100 vs. <100
      previous cystectomies, p=0.021), and daytime continence (p=0.032). CONCLUSION: In
      the present study, we report health-related QoL outcomes in a contemporary
      patient cohort and confirm preoperative ECOG status, surgeon experience and
      daytime incontinence as independent prognostic features for a good postoperative
      QoL.

PMID- 24893917
TI  - Injuries from firearms in hunting activities.
AB  - BACKGROUND: Recreational hunting is a very popular sport, and frequently involves
      firearms. Few studies address the pattern of firearm injuries occurring with
      hunting and how they differ from firearm injuries not associated with hunting.
      PURPOSE: A nation wide database will provide an overall perspective of the scope
      of the problem and types of injuries. METHODS: Our data were obtained from the
      Inter-University Consortium for Political and Social Research Firearm Injury
      Surveillance Study 1993-2008 (ICPSR 30543). It was statistically analyzed for
      demographic and injury patterns using SUDAAN 10TM software. A p < 0.05 was
      considered to be statistically significant. RESULTS: There were 1,841,269 ED
      visits for firearm related injuries 1993-2008; 35,970 were involved in hunting
      (1.95%). Hunters were older than non-hunters (34.5 vs. 26.7 years, p < 0.0001).
      Handguns were involved in 48% of the non-hunters and 5.3% of the hunters (p <
      0.0001). The injury was unintentional in 99.4% of hunters; for non-hunters 32.1%
      were unintentional and 60.7% assaults. The majority of the hunting injuries
      presented to small hospitals (65.9%) while the majority of non-hunting injuries
      presented to the large (27.0%) and very large (35.0%) hospitals. Hunters were
      nearly all Caucasian (92%). In hunters, 57% were shot compared to 77% in non
      hunters. The most common diagnosis in hunters was a laceration (42%) compared to
      a puncture in non-hunters (41%). The head and neck accounted for nearly one-half
      of the injuries in hunters (47%); for non-hunters it was the head and neck (29%)
      and the leg/foot (24%). Mortality was 0.6% for hunters and 5.3% for non-hunters.
      The use of alcohol and being involved in antisocial behaviours was much higher in
      the non-hunters. The estimated incidence of a firearm injury associated with
      hunting activities was 9 per 1 million hunting days. CONCLUSION: Hunters injured
      by firearms were nearly all Caucasian, older than non-hunters, did not involve
      handguns, presented to small hospitals, often sustained unintentional injuries
      and were not shot; most commonly injured in the head and neck, and had an overall
      mortality of 0.6%. These data can be a reference for future studies regarding
      hunting injuries associated with firearms.

PMID- 24893916
TI  - Effect of S-methyl-l-thiocitrulline dihydrochloride on rat micturition reflex.
AB  - OBJECTIVE: To evaluate the effect of neuronal nitric oxide synthase on the
      striated urethral sphincter and the urinary bladder. MATERIALS AND METHODS: A
      coaxial catheter was implanted in the proximal urethra and another one in the
      bladder of female rats, which were anesthetized with subcutaneous injection of
      urethane. The urethral pressure with saline continuous infusion and bladder
      isovolumetric pressure were simultaneously recorded. Two groups of rats were
      formed. In group I, an intrathecal catheter was implanted on the day of the
      experiment at the L6-S1 level of the spinal cord; in group II, an
      intracerebroventricular cannula was placed 5-6 days before the experiment.
      RESULTS: It was verified that the group treated with S-methyl-L-thio-citrulline,
      via intrathecal pathway, showed complete or partial inhibition of the urethral
      sphincter relaxation and total inhibition of the micturition reflexes. The
      urethral sphincter and the detrusor functions were recovered after L-Arginine
      administration. When S-methyl-Lthio-citrulline was administered via
      intracerebroventricular injection, there was a significant increase of urethral
      sphincter tonus while preserving the sphincter relaxation and the detrusor
      contractions, at similar levels as before the use of the drugs. Nevertheless
      there was normalization of the urethral tonus when L-Arginine was applied.
      CONCLUSIONS: The results indicate that, in female rats anaesthetized with
      urethane, the nNOS inhibitor administrated through the intrathecal route inhibits
      urethral sphincter relaxation, while intracerebroventricular injection increases
      the sphincter tonus, without changing bladder function. These changes were
      reverted by L-Arginine administration. These findings suggest that the urethral
      sphincter and detrusor muscle function is modulated by nitric oxide.

PMID- 24893918
TI  - Trends in moderate to severe paediatric trauma in Central Netherlands.
AB  - INTRODUCTION: Trend analyses of hospital discharge data can raise signals for
      prevention policies, but are often flawed by changes in health care consumption.
      This is a trend analysis of the clinical incidence of paediatric trauma that used
      international criteria to overcome this bias. The objective is to describe trends
      in clinical incidence of moderate to severe paediatric trauma, and to identify
      target groups for prevention activities. PATIENTS AND METHODS: Included were all
      paediatric trauma patients (0-18 years) that were discharged from the hospitals
      of trauma care region Central Netherlands from 1996 to 2009. Selection was made
      on ISS >= 4, and on trauma related International Classification of Diseases
      diagnostic codes, and trauma related external causes of injury and poisoning
      codes. Trend analyses were performed using Poisson loglinear regression with
      correction for age and gender. RESULTS: 23,682 Patients were included, the mean
      incidence rate was 477/100,000 person-years. Since 2001 the incidence rate of
      moderate to severe trauma increased with 1.1% annually (95% confidence interval
      (CI) 0.7-1.5), caused by an increase of falls (3.9%, 95% CI 3.3-4.5), sport
      injuries (5.4%, 95% CI 4.3-6.5), and bicycle injuries (3.8%, 95% CI 2.8-4.8). The
      incidence of falls and sport injuries peaked in young children (0-9) and older
      boys (10-18) respectively. Bicycle injuries affected all children between 5 and
      18. CONCLUSIONS: The incidence of paediatric trauma in the centre of the
      Netherlands increased since 2001. Trend analyses on moderate and severe injuries
      may identify target groups for prevention in a trauma region.

PMID- 24893919
TI  - Reoperation following open reduction and plate fixation of displaced mid-shaft
      clavicle fractures.
AB  - BACKGROUND: Operative fixation of displaced, mid-shaft clavicle fractures has
      become an increasingly common practice. With this emerging trend, data describing
      patient outcomes with longer follow-up are necessary. PATIENTS AND METHODS: We
      retrospectively reviewed the medical records of subjects treated with plate
      fixation for displaced mid-shaft clavicle fractures from 2003 to 2009 at a Level
      I trauma hospital. All subjects were greater than 12 months post-index surgery.
      Treatment involved ORIF with either a low-contact dynamic compression plate
      (LCDC) or a contoured plate (pre-contoured or pelvic reconstruction plate). Our
      primary outcome was reoperation for any indication. RESULTS: 143 subjects were
      included. The mean age was 36 +/- 14 years and the mean time to reoperation or
      chart review was 33 months. Contoured plates were used in 64% of cases and LCDC
      plates were used in the remaining subjects. Twenty-nine subjects (20%) underwent
      reoperation: 23.5% of subjects treated with LCDC plates and 18.5% of subjects
      treated with contoured plates (p=0.52). Indications for reoperation included
      implant irritation (n=25), implant failure (n=2), and non-union (n=2). There was
      near statistically significant association with reoperation and female gender
      (p=0.05) but no association between reoperation and age (p=0.14), fracture class
      (p=0.53), plate type (p=0.49), or plate location (p=0.93). The mean QuickDASH
      score for the population surveyed was 8.8 (5.5-12.1; 95% CI) with near
      statistically significant and clinically relevant difference between those
      considering reoperation and those not 22.3 (8.6-36.0; 95% CI) versus 6.7 (3.6
      9.8; 95% CI). CONCLUSIONS: This study represents a large series of displaced
      clavicle fractures treated with open reduction and plate fixation. Reoperation
      following plate fixation is relatively common, but primarily due to implant
      irritation. No difference in reoperation rates between plate types or location
      could be detected in our current sample size. Also, excellent functional outcomes
      continue to be observed several years after clavicle fracture fixation.

PMID- 24893920
TI  - Pantoprazole increases cell viability and function of primary human osteoblasts
      in vitro.
AB  - Proton pump inhibitors (PPIs) are a class of drugs that irreversibly inhibit the
      H(+)/K(+)-ATPase in gastric parietal cells. Since an association between PPI use
      and increased fracture risk has been found, the aim of this study was to detect
      potential adverse effects of pantoprazole, a representative of the PPIs, on
      primary human osteoblasts in vitro. The isolated cells were stimulated with
      pantoprazole concentrations ranging from 0 MUg/ml to 10 MUg/ml. Changes in
      proliferation, total cell number, viability, cytotoxicity, alkaline phosphatase
      activity, total protein synthesis and gene expression on mRNA level were
      determined over a period of 7 days. Pantoprazole stimulation resulted in
      increased viability and decreased cytotoxicity in the osteoblasts. The
      proliferation rate was stable and so was the relative cell number. Only at the
      highest pantoprazole concentration on day 7, a slight decrease of the cell number
      was detected. Alkaline phosphatase activity increased over the tested period
      under exposure to pantoprazole (p < 0.05 at 3 MUg/ml and 10 MUg/ml pantoprazole).
      Osteoblast-specific gene expression was increased through pantoprazole
      stimulation compared to the control on day 3. Towards day 7, gene expression
      returned to baseline levels or decreased slightly compared to unexposed cells.
      Interestingly, this in vitro experiment detected no evidence of adverse effects
      of PPIs on primary human osteoblasts. Osteoblasts were rather more viable with
      increased mitochondrial activity, gene expression and protein synthesis under
      pantoprazole stimulation. Therefore, these in vitro results do not suggest that
      impaired osteoblast function is the cause of an increased fracture risk in
      patients under PPI therapy.

PMID- 24893921
TI  - The growth hormone receptor exon 3 polymorphism is not associated with height or
      metabolic traits in healthy young adults.
AB  - CONTEXT: The GHR polymorphisms contribution to the interindividual variability in
      prenatal and postnatal growth as well as to metabolic traits is controversial.
      OBJECTIVE: The aim of this study is to analyze the association of the GHRfl/d3
      polymorphism with prenatal and postnatal growth and metabolic outcomes in adult
      life and to compare the genotype distribution in different populations. DESIGN:
      385 community healthy subjects followed from birth to adult life (23-25years old)
      were grouped according to birth size: small-SGA (n=130, 62 males), appropriate
      AGA (n=162, 75 males) and large for gestational age-LGA (n=93, 48 males).
      GHRfl/d3 genotype distribution and its potential association with anthropometric
      (at birth, childhood and adult life) and metabolic features (in adult life) were
      analyzed and compared with data obtained from a systematic review of GHRfl/d3
      association studies (31 articles). RESULTS: The frequency of the GHR d3/d3
      genotype was lower in the LGA (chi2 p=0.01); SGA and AGA subjects exhibited an
      increased chance of the d3/d3 genotype (OR=3.58; 95%CI: 1.55; 8.24) and (OR=2.39;
      95%CI: 1.02; 5.62), respectively. Despite the different prevalence among
      different birth size groups, in adults, GHRfl/d3 genotype was not associated with
      height, plasma IGF1 levels or metabolic phenotype and cardiovascular risk.
      GHRfl/d3 genotype distributions in AGA, SGA and LGA groups were comparable with
      those found in subjects of European origin but not with those of Asian ancestry.
      CONCLUSIONS: The GHRd3 genotype was negatively associated with birth size but it
      was not associated with adult height or weight, plasma IGF1, metabolic phenotype
      or any marker of increased cardiovascular risk in young adults.

PMID- 24893922
TI  - Determination of calcium mobility in alkaline-cooked grounded corn in presence of
      a magnetic field.
AB  - The mobility of calcium ions in corn dough prepared using commercial powder of
      alkaline-cooked grounded-corn kernel was determined in presence of a magnetic
      field. The ionic conduction was determined using 2 electrodes placed at 2
      consecutives corners of the square samples: the excitation line was along one
      edge. Three different calcium concentrations [Ca] and 3 different magnetic field
      B conditions (B0, B-, B+) were analyzed; in all cases, the same amount of water
      was used. The relaxation times tau were determined by measuring the ionic current
      with and, immediately after, without excitation voltage. An empirical model,
      based on the obstruction effect characteristic of the ionic conduction and on the
      effect of the magnetic field B on the motion of the ions, was developed to
      explain the dependence of tau with [Ca] and B. The threshold concentration at
      which the Ca ions are not longer linked chemically to the starch molecules and
      move freely in the dough interior was obtained. PRACTICAL APPLICATION: It was
      possible to determine the free-to-link threshold concentration for calcium ions
      in alkaline-cooked grounded-corn kernel dough; this is near 1.5% Ca. The magnetic
      field allows to separate and measuring different types of ions; a model to
      explain the dependence of the relaxation time with the magnetic field was
      included.

PMID- 24893923
TI  - Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.
AB  - BACKGROUND AND OBJECTIVE: The ossein-hydroxyapatite complex (OHC) is a
      microcrystalline form of calcium which provides a number of additional minerals
      (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I
      collagen, type I insulin growth factor I and II, transforming growth factor beta)
      associated with bone metabolism. The objective of this review is to examine the
      role of OHC in preventing bone loss in different conditions. MATERIAL AND
      METHODS: A review of clinical trials assessing the relationship between OHC and
      bone loss was made using the following data sources: Medline (from 1966 to
      December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to
      December 2013), contact with companies marketing the supplements studied, and
      reference lists. RESULTS: Different randomized, clinical trials and meta-analysis
      suggest that OHC is more effective than calcium supplements in maintaining bone
      mass in postmenopausal women and in different conditions related to bone loss. In
      addition, OHC improves pain symptoms and accelerates fracture consolidation in
      patients with osteopenia or osteoporosis. CONCLUSION: The ossein-hydroxyapatite
      complex is significantly more effective in preventing bone loss than calcium
      carbonate.

PMID- 24893924
TI  - Rapid identification of gram negative bacteria from blood culture broth using
      MALDI-TOF mass spectrometry.
AB  - An important role of the clinical microbiology laboratory is to provide rapid
      identification of bacteria causing bloodstream infection. Traditional
      identification requires the sub-culture of signaled blood culture broth with
      identification available only after colonies on solid agar have matured. MALDI
      TOF MS is a reliable, rapid method for identification of the majority of
      clinically relevant bacteria when applied to colonies on solid media. The
      application of MALDI-TOF MS directly to blood culture broth is an attractive
      approach as it has potential to accelerate species identification of bacteria and
      improve clinical management. However, an important problem to overcome is the pre
      analysis removal of interfering resins, proteins and hemoglobin contained in
      blood culture specimens which, if not removed, interfere with the MS spectra and
      can result in insufficient or low discrimination identification scores. In
      addition it is necessary to concentrate bacteria to develop spectra of sufficient
      quality. The presented method describes the concentration, purification, and
      extraction of Gram negative bacteria allowing for the early identification of
      bacteria from a signaled blood culture broth.

PMID- 24893925
TI  - Isolation of double negative alphabeta T cells from the kidney.
AB  - There is currently no standard protocol for the isolation of DN T cells from the
      non-lymphoid tissues despite their increasingly reported involvement in various
      immune responses. DN T cells are a unique immune cell type that has been
      implicated in regulating immune and autoimmune responses and tolerance to
      allotransplants(1-6). DN T cells are, however, rare in peripheral blood and
      secondary lymphoid organs (spleen and lymph nodes), but are major residents of
      the normal kidney. Very little is known about their pathophysiologic function(7)
      due to their paucity in the periphery. We recently described a comprehensive
      phenotypic and functional analysis of this population in the kidney(8) in steady
      state and during ischemia reperfusion injury. Analysis of DN T cell function will
      be greatly enhanced by developing a protocol for their isolation from the kidney.
      Here, we describe a novel protocol that allows isolation of highly pure ab CD4+
      CD8+ T cells and DN T cells from the murine kidney. Briefly, we digest kidney
      tissue using collagenase and isolate kidney mononuclear cells (KMNC) by density
      gradient. This is followed by two steps to enrich hematopoietic T cells from 3%
      to 70% from KMNC. The first step consists of a positive selection of
      hematopoietic cells using a CD45+ isolation kit. In the second step, DN T cells
      are negatively isolated by removal of non-desired cells using CD4, CD8, and MHC
      class II monoclonal antibodies and CD1d alpha-galcer tetramer. This strategy
      leads to a population of more than 90% pure DN T cells. Surface staining with the
      above mentioned antibodies followed by FACs analysis is used to confirm purity.

PMID- 24893926
TI  - Polysome fractionation and analysis of mammalian translatomes on a genome-wide
      scale.
AB  - mRNA translation plays a central role in the regulation of gene expression and
      represents the most energy consuming process in mammalian cells. Accordingly,
      dysregulation of mRNA translation is considered to play a major role in a variety
      of pathological states including cancer. Ribosomes also host chaperones, which
      facilitate folding of nascent polypeptides, thereby modulating function and
      stability of newly synthesized polypeptides. In addition, emerging data indicate
      that ribosomes serve as a platform for a repertoire of signaling molecules, which
      are implicated in a variety of post-translational modifications of newly
      synthesized polypeptides as they emerge from the ribosome, and/or components of
      translational machinery. Herein, a well-established method of ribosome
      fractionation using sucrose density gradient centrifugation is described. In
      conjunction with the in-house developed "anota" algorithm this method allows
      direct determination of differential translation of individual mRNAs on a genome
      wide scale. Moreover, this versatile protocol can be used for a variety of
      biochemical studies aiming to dissect the function of ribosome-associated protein
      complexes, including those that play a central role in folding and degradation of
      newly synthesized polypeptides. 

PMID- 24893927
TI  - Synchronized necrotic death of attached hepatocytes mediated via gap junctions.
AB  - Extensive studies have unveiled the intracellular molecular signaling pathways of
      cell death. To better understand cell death in tissues, it is important to
      investigate the influence of neighboring cells on the response to death stimuli.
      By time-lapse microscopy, we found that cells in couplets (two hepatocytes
      attached to each other) died independently when stimulated with anti-Fas antibody
      and staurosporine, whereas acetaminophen (APAP) and aryl alcohol caused
      synchronized cell death although its timing varied among different couplets.
      Synchronized death of couplets was not caused by APAP when hepatocytes were
      deficient in both Connexin26 and Connexin32, indicating a crucial role of gap
      junctions in the synchronized death process. We also demonstrated that APAP
      sensitive male hepatocytes were protected by attachment to APAP-insensitive
      female hepatocytes, with this protection being dependent on gap junctions. These
      findings indicate that APAP-induced and aryl alcohol-induced necrotic death of
      hepatocytes is modulated by attached neighboring cells via gap junctions. 

PMID- 24893929
TI  - Tailoring gadolinium-doped ceria-based solid oxide fuel cells to achieve 2 W cm(
      2) at 550  degrees C.
AB  - Low-temperature operation is necessary for next-generation solid oxide fuel cells
      due to the wide variety of their applications. However, significant increases in
      the fuel cell losses appear in the low-temperature solid oxide fuel cells, which
      reduce the cell performance. To overcome this problem, here we report
      Gd0.1Ce0.9O1.95-based low-temperature solid oxide fuel cells with nanocomposite
      anode functional layers, thin electrolytes and core/shell fibre-structured
      Ba0.5Sr0.5Co0.8Fe0.2O3-delta-Gd0.1Ce0.9O1.95 cathodes. In particular, the report
      describes the use of the advanced electrospinning and Pechini process in the
      preparation of the core/shell-fibre-structured cathodes. The fuel cells show a
      very high performance of 2 W cm(-2) at 550  degrees C in hydrogen, and are stable
      for 300 h even under the high current density of 1 A cm(-2). Hence, the results
      suggest that stable and high-performance solid oxide fuel cells at low
      temperatures can be achieved by modifying the microstructures of solid oxide fuel
      cell components.

PMID- 24893928
TI  - The extent of papillary muscle approximation affects mortality and durability of
      mitral valve repair for ischemic mitral regurgitation.
AB  - BACKGROUND: Since reduction annuloplasty alone for ischemic mitral regurgitation
      (MR) cannot prevent late recurrence of MR or improve survival for those with left
      ventricular (LV) dysfunction, and the surgical approach to this etiology is still
      controversial, we conducted a study to assess the efficacy of the additional
      papillary muscle approximation (PMA) procedure for ischemic MR by comparing the
      different subtypes of PMA. METHODS: We studied 45 patients who underwent mitral
      annuloplasty and papillary muscle approximation (PMA) for ischemic MR between
      2003 and 2012. Papillary muscles were approximated entirely (cPMA: complete PMA,
      n = 32) through an LV incision or partially from the tips to mid-parts (iPMA:
      incomplete PMA, n = 13) through the mitral and aortic valves. Twenty-three
      patients with cPMA also underwent LV plasty (LVP). We assessed the outcomes after
      PMA by comparing cPMA and iPMA. RESULTS: The baseline MR grade, NYHA class, LV
      end-diastolic diameter, and LV ejection fraction (LVEF) were 2.8 +/- 1.0, 3.2 +/-
      0.6, 67 +/- 6 mm, and 30 +/- 10%, respectively. There were no significant
      differences in these parameters among those with iPMA, cPMA/LVP-, and cPMA/LVP+,
      though iPMA patients had better LVEF than others. Three patients died before
      discharge and 12 died during the follow-up. Recurrence of grade 2+ and 3+ MR
      occurred in 8 and 2 patients, respectively. Reoperation for recurrent MR was
      performed only for the 2 patients with recurrence of grade 3+ MR. The cPMA was
      associated with lower mortality (log-rank P = 0.020) and a lower rate of
      recurrence of MR >=2+ (log-rank P = 0.005) than iPMA. In contrast, there were no
      significant differences in the mortality (log-rank P = 0.45) and rate of
      recurrence (log-rank P = 0.98) between those with cPMA/LVP- and cPMA/LVP+. The 4
      year survival rate and rate of freedom from recurrence of MR >=2+ were 83% and
      85% for those with cPMA, repectively. In contrast, the rates were 48% and 48% for
      those with iPMA, respectively. CONCLUSIONS: Complete PMA could be associated with
      lower postoperative mortality and higher durability of mitral valve repair for
      ischemic MR.

PMID- 24893931
TI  - Obstetrical brachial plexus injuries: late functional results of the Steindler
      procedure.
AB  - We reviewed late functional results of a modified Steindler procedure in patients
      with obstetrical brachial plexus palsy and poor active elbow flexion. From 1982
      to 2005, we reviewed final functional results and complications of 27 cases with
      flexion weakness of the elbow secondary to obstetrical brachial plexus injury,
      treated with a modified Steindler procedure. At the end of the follow-up, the
      mean active elbow flexion was 97 degrees  and the mean extensor lag was 10
      degrees . In the long-term follow-up, the modified Steindler procedure maintained
      good results in 67% of the cases in our series, and this percentage raised by 82%
      when the wrist extensor was present or restored before the Steindler procedure.
      There were poor results in 19% of the patients, but no major complications. 

PMID- 24893930
TI  - Do gender differences in primary PCI mortality represent a different adherence to
      guideline recommended therapy? a multicenter observation.
AB  - BACKGROUND: It is uncertain whether gender differences in outcome after primary
      percutaneous coronary intervention (PCI) are only attributable to different
      baseline characteristics or additional factors. METHODS: Databases of two German
      myocardial infarction network registries were combined with a total of 1104
      consecutive patients admitted with acute ST-elevation myocardial infarction
      (STEMI) and treated according to standardized protocols. RESULTS: Approximately
      25% of patients were females. Mean age (69 vs 61 years), incidence of diabetes
      (28% vs 20%), hypertension (68 vs 58%) and renal insufficiency (26% vs 19%) was
      significantly higher compared to males. Mean prehospital delay was numerically
      longer in females (227 vs 209 min) as was in hospital delay (35 vs 30 min). PCI
      was finally performed in 92% of females and 95% of males with comparable
      procedural success (95% vs 97%). Use of drug eluting stents (55% vs 68%) and
      application of GP 2b 3a blockers (75% vs 89%) was significantly less frequent in
      women. At discharge, prescription of beta blockers and lipid lowering drugs was
      also significantly lower in females (84% vs 90% and 71% vs 84%). Unadjusted in
      hospital mortality was significantly higher in females (10% vs 5%) without
      attenuation after 12 months. Adjusted mortality however did not differ
      significantly between genders. CONCLUSION: Higher unadjusted mortality in females
      after primary PCI was accompanied by significant differences in baseline
      characteristics, interventional approach and secondary prophylaxis in spite of
      the same standard of care. Lower guideline adherence seems to be less gender
      specific but rather a manifestation of the risk-treatment paradox.

PMID- 24893933
TI  - Participants' perceptions and understanding of a malaria clinical trial in
      Bangladesh.
AB  - BACKGROUND: Existing evidence suggests that there is often limited understanding
      among participants in clinical trials about the informed consent process,
      resulting in their providing consent without really understanding the purpose of
      the study, specific procedures, and their rights. The objective of the study was
      to determine the subjects' understanding of research, perceptions of
      voluntariness and motivations for participation in a malaria clinical trial.
      METHODS: In this study semi-structured interviews of adult clinical trial
      participants with uncomplicated falciparum malaria were conducted in Ramu Upazila
      Health Complex, in Bangladesh. RESULTS: Of 16 participants, the vast majority
      (81%) were illiterate. All subjects had a 'therapeutic misconception' i.e. the
      trial was perceived to be conducted primarily for the benefit of individual
      patients when in fact the main objective was to provide information to inform
      public health policy. From the patients' perspective, getting well from their
      illness was their major concern. Poor actual understanding of trial specific
      procedures was reported despite participants' satisfaction with treatment and
      nursing care. CONCLUSION: There is frequently a degree of overlap between
      research and provision of clinical care in malaria research studies. Patients may
      be motivated to participate to research without a good understanding of the
      principal objectives of the study despite a lengthy consent process. The findings
      suggest that use of a standard consent form following the current ICH-GCP
      guidelines does not result in achieving fully informed consent and the process
      should be revised, simplified and adapted to individual trial settings.

PMID- 24893932
TI  - An eight-miRNA signature as a potential biomarker for predicting survival in lung
      adenocarcinoma.
AB  - BACKGROUND: Lung adenocarcinoma is a heterogernous disease that creates
      challenges for classification and management. The purpose of this study is to
      identify specific miRNA markers closely associated with the survival of LUAD
      patients from a large dataset of significantly altered miRNAs, and to assess the
      prognostic value of this miRNA expression profile for OS in patients with LUAD.
      METHODS: We obtained miRNA expression profiles and corresponding clinical
      information for 372 LUAD patients from The Cancer Genome Atlas (TCGA), and
      identified the most significantly altered miRNAs between tumor and normal
      samples. Using survival analysis and supervised principal components method, we
      identified an eight-miRNA signature for the prediction of overall survival (OS)
      of LUAD patients. The relationship between OS and the identified miRNA signature
      was self-validated in the TCGA cohort (randomly classified into two subgroups: n
      = 186 for the training set and n = 186 for the testing set). Survival receiver
      operating characteristic (ROC) analysis was used to assess the performance of
      survival prediction. The biological relevance of putative miRNA targets was also
      analyzed using bioinformatics. RESULTS: Sixteen of the 111 most significantly
      altered miRNAs were associated with OS across different clinical subclasses of
      the TCGA-derived LUAD cohort. A linear prognostic model of eight miRNAs (miR-31,
      miR-196b, miR-766, miR-519a-1, miR-375, miR-187, miR-331 and miR-101-1) was
      constructed and weighted by the importance scores from the supervised principal
      component method to divide patients into high- and low-risk groups. Patients
      assigned to the high-risk group exhibited poor OS compared with patients in the
      low-risk group (hazard ratio [HR] = 1.99, P <0.001). The eight-miRNA signature is
      an independent prognostic marker of OS of LUAD patients and demonstrates good
      performance for predicting 5-year OS (Area Under the respective ROC Curves [AUC]
      = 0.626, P = 0.003), especially for non-smokers (AUC = 0.686, P = 0.023).
      CONCLUSIONS: We identified an eight-miRNA signature that is prognostic of LUAD.
      The miRNA signature, if validated in other prospective studies, may have
      important implications in clinical practice, in particular identifying a subgroup
      of patients with LUAD who are at high risk of mortality.

PMID- 24893934
TI  - Research and clinical applications of optical coherence tomography in invasive
      cardiology: a review.
AB  - In cardiology, optical coherence tomography (OCT) is an invasive imaging
      technique based on the principle of light coherence. This system was developed to
      obtain three-dimensional high resolution images to examine coronary artery normal
      and/or pathological structure. This technique replaces the ultrasound used by its
      main alternative procedure, intravascular ultrasound, by a near-infrared light
      source. Acute coronary syndromes due to atherosclerotic vascular disease are the
      leading cause of mortality in developed and developing countries. As a
      consequence, intravascular imaging systems became an important area of research
      and 1991 marks the first use of OCT in coronary artery observations. Since its
      first appearance in invasive cardiology, OCT maintains a strong presence in the
      research environments for the identification of vulnerable plaques, as it is able
      to overcome difficulties presented by other techniques such as virtual
      intravascular ultrasound, near-infrared spectroscopy, and histology. Moreover,
      OCT is increasingly being used in the clinical practice as a guide during
      coronary interventions and in the assessment of vascular response after coronary
      stent implantation. This review focuses on the relevance of OCT in research and
      clinical applications in the field of invasive cardiology and discusses the
      future directions of the field. 

PMID- 24893935
TI  - Clinical diagnosis and management of large vessel vasculitis: giant cell
      arteritis.
AB  - Large vessel vasculitis (LVV) covers a spectrum of primary vasculitides
      predominantly affecting the aorta and its major branches. The two main subtypes
      are giant cell arteritis (GCA) and Takayasu arteritis (TA). Less commonly LVV
      occurs in various other diseases. Clinical manifestations result from vascular
      stenosis, occlusion, and dilation, sometimes complicated by aneurysm rupture or
      dissection. Occasionally LVV is discovered unexpectedly on pathological
      examination of a resected aortic aneurysm. Clinical evaluation is often
      unreliable in determining disease activity. Moreover, the diagnostic tools are
      imperfect. Acute phase reactants can be normal at presentation and available
      imaging modalities are more reliable in delineating vascular anatomy than in
      providing reliable information on degree of vascular inflammation.
      Glucocorticoids are the mainstay of therapy of LVV. Patients may develop
      predictable adverse effects from long-term glucocorticoid use. Several steroid
      sparing agents have also shown some promise and are currently in use.
      Endovascular revascularization procedures and open surgical treatment for
      aneurysms and dissections are sometimes necessary, but results are not always
      favorable and relapses are common. This article, the first in a series of two,
      will be devoted to GCA and isolated (idiopathic) aortitis, while TA will be
      covered in detail in the next article. 

PMID- 24893936
TI  - Clinical diagnosis and management of large vessel vasculitis: Takayasu arteritis.
AB  - Takayasu arteritis (TA) is 1 of the 2 main causes of large vessel vasculitides
      (LVV), giant cell arteritis being the other. LVV can also develop in various
      other systemic diseases. In TA, a wide variety of symptoms result from vascular
      stenoses, occlusions, and dilation. Aneurysms may develop and may occasionally
      dissect or rupture. Disease activity can sometimes be difficult to assess
      clinically. Diagnostic modalities also have their shortcomings. Often, acute
      phase reactants do not accurately detect disease activity. Available vascular
      imaging modalities may be acceptable in defining vascular anatomy, but are
      notoriously inaccurate in delineating vascular inflammation. Glucocorticoids
      remain the cornerstone of therapy in TA, in spite of foreseeable long term side
      effects. In addition, several steroid-sparing agents are also being used, often
      based on promising results from small uncontrolled studies. Rarely, endovascular
      revascularization procedures are necessary. Resection of critical-sized aortic
      aneurysms and repair of aortic dissections are occasionally warranted as
      lifesaving procedures. The long term outcome of surgical intervention is often
      unfavorable and relapses are not uncommon. In addition to TA, other less commonly
      encountered causes of LVV are also briefly discussed in this review. 

PMID- 24893937
TI  - Public reporting of PCI outcomes: for better or for worse.
AB  - Public reporting of PCI outcomes has had a polarizing effect on the cardiology
      community. The potential benefits of public reporting are many, but a host of
      unintended consequences have likely mitigated the anticipated positive impact of
      current reporting systems. In this review, we discuss what the goals of public
      disclosure are, the limitations of current reporting systems and the resultant
      unintended consequences. We also offer a perspective on future directions with a
      view to ensuring the benefits of public reporting while minimizing the risk of
      unintended consequences.

PMID- 24893939
TI  - Functional genomics of the 9p21.3 locus for atherosclerosis: clarity or
      confusion?
AB  - The 9p21.3 locus was the first to yield to genome-wide association studies (GWAS)
      seeking common genetic variants predisposing to increased risk of coronary artery
      atherosclerotic disease (CAD). The 59 single nucleotide polymorphisms that show
      highest association with CAD are clustered in a region 100,000 to 150,000 base
      pairs 5' to the cyclin-dependent kinase inhibitors CDKN2B (coding for p15(ink4b))
      and CDKN2A (coding for p16(ink4a) and p14(ARF)). This region also covers the 3'
      end of a long noncoding RNA transcribed antisense to CDKN2B (CDKN2BAS, aka ANRIL
      for antisense noncoding RNA at the ink4 locus) whose expression has been linked
      to chromatin remodeling at the locus. Despite intensive investigation over the
      past 7 years, the functional significance of the 9p21.3 locus remains elusive.
      Other variants at this locus have been associated with glaucoma, glioma, and type
      2 diabetes mellitus, diseases that implicate tissue-resident macrophages. Here,
      we review the evidence that genetic variants at 9p21.3 disrupt tissue-specific
      enhancers and propose new insights to guide future studies. 

PMID- 24893938
TI  - Heart failure with preserved ejection fraction: current understandings and
      challenges.
AB  - Heart failure (HF) is the leading cause of hospitalization among older adults and
      the prevalence is growing with the aging populations in western countries.
      Approximately one-half of patients with HF have preserved ejection fraction
      (HFpEF). In contrast to HF with reduced EF (HFrEF), there is no proven effective
      treatment for HFpEF. The pathophysiology of HFpEF is complex, and the dominant
      mechanisms leading to symptoms of HF often vary between afflicted patients,
      confounding efforts to apply "one-size fits all" types of therapeutic approaches.
      Current treatment strategies focus on control of volume status and comorbidities,
      but future research aimed at individualized therapies holds promise to improve
      outcomes in this increasingly prevalent form of cardiac failure. 

PMID- 24893940
TI  - Exome sequencing: new insights into lipoprotein disorders.
AB  - Several next generation sequencing platforms allow for a DNA-to-diagnosis
      protocol to identify the molecular basis of monogenic dyslipidemias. However,
      recent reports of the application of whole genome or whole exome sequencing in
      families with severe dyslipidemias have largely identified genetic variants in
      known lipid genes. To date, high-throughput DNA sequencing in families with
      previously uncharacterized monogenic dyslipidemias, have failed to reveal new
      genes for regulation of plasma lipids. This suggests that rather than sequencing
      whole genomes or exomes, most patients with monogenic dyslipidemias could be
      diagnosed using a more dedicated approach that focuses primarily on genes already
      known to act within lipoprotein metabolic pathways. 

PMID- 24893942
TI  - Flavobacterium faecale sp. nov., an agarase-producing species isolated from
      stools of Antarctic penguins.
AB  - Taxonomic studies were performed on an agarase-producing strain, designated
      WV33(T), isolated from faeces of Antarctic penguins. Cells of strain WV33(T) were
      Gram-staining-negative, strictly aerobic, orange and rod-shaped. Strain WV33(T)
      displayed agarase activity and was able to utilize galactose as a sole carbon
      source. 16S rRNA gene sequence analysis revealed that strain WV33(T) was closely
      related to Flavobacterium algicola TC2(T) (98.0% similarity), F. frigidarium ATCC
      700810(T) (96.9%) and F. frigoris LMG 21922(T) (96.1%). The predominant cellular
      fatty acids were iso-C(15 : 1) G, iso-C(15 : 0), C(15 : 0), C(16 : 0) and summed
      feature 3 (comprising iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c). Menaquinone 6
      (MK-6) was the sole quinone identified, and the major pigment was zeaxanthin. The
      major polar lipid was phosphatidylethanolamine. DNA-DNA relatedness of strain
      WV33(T) with respect to its closest phylogenetic neighbours was 25% for F.
      algicola NBRC 102673(T), 23% for F. frigidarium DSM 17623(T) and 21% for F.
      frigoris DSM 15719(T). The DNA G+C content of strain WV33(T) was 37+/-0.6 mol%.
      Based on the phenotypic, chemotaxonomic and phylogenetic data, strain WV33(T) is
      concluded to represent a novel species of the genus Flavobacterium, for which the
      name Flavobacterium faecale sp. nov. is proposed. The type strain is WV33(T) ( =
      KCTC 32457(T) = CECT 8384(T)).

PMID- 24893943
TI  - Rhizocola hellebori gen. nov., sp. nov., an actinomycete of the family
      Micromonosporaceae containing 3,4-dihydroxydiaminopimelic acid in the cell-wall
      peptidoglycan.
AB  - An actinomycete strain, K12-0602(T), was isolated from the root of a Helleborus
      orientalis plant in Japan. The 16S rRNA gene sequence of strain K12-0602(T)
      showed that it had a close relationship with members of the family
      Micromonosporaceae and the 16S rRNA gene sequence similarity values between
      strain K12-0602(T) and type strains of type species of 27 genera belonging to the
      family Micromonosporaceae were below 96.2%. MK-9 (H4) and MK-9 (H6) were detected
      as major menaquinones, and galactose, xylose, mannose and ribose were present in
      the whole-cell hydrolysate. The acyl type of the peptidoglycan was glycolyl.
      Major fatty acids were iso-C(15 : 0), iso-C(16 : 0), C(17 : 1)omega9c and anteiso
      C(17 : 0). Phosphatidylethanolamine was detected as the phospholipid
      corresponding to phospholipid type II. The G+C content of the genomic DNA was 67
      mol%. Analyses of the cell-wall peptidoglycan by TLC and LC/MS showed that it was
      composed of alanine, glycine, hydroxylglutamic acid and an unknown amino acid,
      which was subsequently determined to be 3,4-dihydroxydiaminopimelic acid using
      instrumental analyses, including NMR and mass spectrometry. On the basis of the
      phylogenetic analysis and chemotaxonomic characteristics, strain K12-0602(T)
      represents a novel species of a new genus in the family Micromonosporaceae, for
      which the name Rhizocola hellebori gen. nov., sp. nov. is proposed. The type
      strain of the type species is K12-0602(T) ( = NBRC 109834(T) = DSM 45988(T)).
      This is the first report, to our knowledge, of 3,4-dihydroxydiaminopimelic acid
      being found as a diamino acid in bacterial cell-wall peptidoglycan.

PMID- 24893941
TI  - Risk stratification and treatment of brugada syndrome.
AB  - The Brugada syndrome (BS) is a hereditary disease characterized by typical
      electrocardiographic alterations (elevation of the ST segment in right precordial
      leads) that affects young individuals without structural heart disease,
      predisposing them to ventricular arrhythmias and sudden death (SD). Several
      genetic mutations of different subunits of the sodium, calcium and potassium
      channel have been involved. The majority of patients with BS remain asymptomatic;
      however, the most frequent symptoms are syncope and/or SD secondary to
      polymorphic ventricular tachycardia (PVT) or ventricular fibrillation (VF).
      Electrocardiographic manifestations of the BS are typically dynamic and
      occasionally only become apparent after the administration of a sodium channel
      blocker or with fever. Risk stratification is mainly based on symptoms and the
      surface electrocardiogram. However, in asymptomatic patients, risk evaluation is
      still controversial and requires further studies. This review provides an updated
      summary of the BS from the point of view of genetic, clinical manifestations,
      risk stratification and management. 

PMID- 24893944
TI  - Brief intervention: a promising framework for child and youth mental health?
AB  - There is a discrepancy between the demand for mental health treatment amongst
      children, young people and their carers, and the capacity of the current service
      system to provide evidence based interventions. Innovative models of care are
      required to redress this discrepancy. One such model is the single session model,
      which provides a single or small number of solution focused sessions targeting
      one or two identified problems. Single session interventions have been trialled
      across a range of presenting concerns including child and youth mental health
      services. This paper provides a rationale for offering a brief focused
      intervention as part of a broader Child and Youth Mental Health Service, and
      introduces a model of how brief intervention fits within a broader system of
      care. 

PMID- 24893945
TI  - Influence of individual cell motility on the 2D front roughness dynamics of
      tumour cell colonies.
AB  - The dynamics of in situ 2D HeLa cell quasi-linear and quasi-radial colony fronts
      in a standard culture medium is investigated. For quasi-radial colonies, as the
      cell population increased, a kinetic transition from an exponential to a constant
      front average velocity regime was observed. Special attention was paid to
      individual cell motility evolution under constant average colony front velocity
      looking for its impact on the dynamics of the 2D colony front roughness. From the
      directionalities and velocity components of cell trajectories in colonies with
      different cell populations, the influence of both local cell density and cell
      crowding effects on individual cell motility was determined. The average dynamic
      behaviour of individual cells in the colony and its dependence on both local
      spatio-temporal heterogeneities and growth geometry suggested that cell motion
      undergoes under a concerted cell migration mechanism, in which both a limiting
      random walk-like and a limiting ballistic-like contribution were involved. These
      results were interesting to infer how biased cell trajectories influenced both
      the 2D colony spreading dynamics and the front roughness characteristics by local
      biased contributions to individual cell motion. These data are consistent with
      previous experimental and theoretical cell colony spreading data and provide
      additional evidence of the validity of the Kardar-Parisi-Zhang equation, within a
      certain range of time and colony front size, for describing the dynamics of 2D
      colony front roughness. 

PMID- 24893946
TI  - Olecranon fractures: factors influencing re-operation.
AB  - PURPOSE: We evaluated factors influencing re-operation in tension band and
      plating of isolated olecranon fractures. METHODS: Four hundred eighty-nine
      patients with isolated olecranon fractures who underwent tension band (TB) or
      open reduction internal fixation (ORIF) from 2003 to 2013 were identified at an
      urban level 1 trauma centre. Medical records were reviewed for patient
      information and complications, including infection, nonunion, malunion, loss of
      function or hardware complication requiring an unplanned surgical intervention.
      Electronic radiographs of these patients were reviewed to identify Orthopaedic
      Trauma Association (OTA) fracture classification and patients who underwent TB or
      ORIF. RESULTS: One hundred seventy-seven patients met inclusion criteria of
      isolated olecranon fractures. TB was used for fixation in 43 patients and ORIF in
      134. No statistical significance was found when comparing complication rates in
      open versus closed olecranon fractures. In a multivariate analysis, the key
      factor in outcome was method of fixation. Overall, there were higher rates of
      infection and hardware removal in the TB compared with the ORIF group.
      CONCLUSIONS: Our results demonstrate that the dominant factor driving re
      operation in isolated olecranon fractures is type of fixation. When controlling
      for all variables, there is an increased chance of re-operation in patients with
      TB fixation.

PMID- 24893947
TI  - Proposed biokinetic model for phosphorus.
AB  - This paper reviews data related to the biokinetics of phosphorus in the human
      body and proposes a biokinetic model for systemic phosphorus for use in updated
      International Commission on Radiological Protection (ICRP) guidance on
      occupational intake of radionuclides. Compared with the ICRP's current
      occupational model for systemic phosphorus (Publication 68, 1994), the proposed
      model provides a more realistic description of the paths of movement of
      phosphorus in the body and greater consistency with experimental, medical, and
      environmental data regarding its time-dependent distribution. For acute uptake of
      (32)P to blood, the proposed model yields roughly a 50% decrease in dose
      estimates for bone surface and red marrow and a six-fold increase in estimates
      for liver and kidney compared with the model of Publication 68. For acute uptake
      of (33)P to blood, the proposed model yields roughly a 50% increase in dose
      estimates for bone surface and red marrow and a seven-fold increase in estimates
      for liver and kidney compared with the model of Publication 68. 

PMID- 24893948
TI  - Combined Orthodontic-surgical Treatment for Skeletal Class III Malocclusion with
      Multiple Impacted Permanent and Supernumerary Teeth: Case Report.
AB  - In this report we describe a combined orthodontic and surgical treatment for a 14
      year-old boy with severe skeletal class III deformity and dental problem. His
      upper posterior primary teeth in the left side were over-retained and 6 maxillary
      teeth (bilateral central incisors and canines, left first and second premolars)
      were impacted, together with 5 supernumerary teeth in both arches. The treatment
      protocol involved extraction of all the supernumerary and deciduous teeth,
      surgical exposure and orthodontic traction of the impacted teeth, a bimaxillary
      orthognathic approach including Lefort I osteotomy. Bilateral sagittal split
      ramus osteotomy (BSSRO) and genioplasty was performed to correct skeletal
      problem. After treatment, all of the impacted teeth were brought to proper
      alignment in the maxillary arch. A satisfied profile and good posterior occlusion
      was achieved. Treatment mechanics and consideration during different stages are
      discussed. 

PMID- 24893949
TI  - Motion sickness prevalence in school children.
AB  - This study aimed to determine the prevalence of motion sickness in schoolchildren
      and related the finding to the postural balance and quality of life. A population
      based cross-sectional study was carried out with 831 children aged 7 to 12 years.
      The frequency of motion sickness was evaluated based on the Motion Sickness
      Susceptibility Questionnaire-Short (MSSQ-short). Postural balance was assessed
      using the Romberg test under different sensory conditions. The Dizziness Handicap
      Inventory was used in order to assess the quality of life. The statistical
      analyses were performed using the chi-square, Kruskal-Wallis, Mann-Whitney, and
      Spearman correlation tests. The prevalence of motion sickness was 43.4 % in car,
      43.2 % on bus, 11.7 % on park swing, and 11.6 % on Ferris wheel. Mean unadjusted
      scores on the MSSQ-short ranged from 5.0 (SE = 0.5) for 10-year-olds to 6.8 (SE =
      0.5) for 9-year-olds. The most prevalent symptoms following the balance tests
      were dizziness (89.2 %), vertigo (54.9 %), headache (10.6 %), and nausea (8.2 %).
      Significant correlations were found between the MSSQ-short score and all postural
      balance tests. Significant correlations were found between the MSSQ and modified
      DHI (Dizziness Handicap Inventory) at all ages. CONCLUSION: The prevalence of
      motion sickness in schoolchildren is greater when in a car or on a bus. An
      association was found between motion sickness and postural balance tests and
      motion sickness and quality of life.

PMID- 24893950
TI  - Factors associated with proceeding to surgical intervention and recurrence of
      primary spontaneous pneumothorax in adolescent patients.
AB  - Primary spontaneous pneumothorax (PSP) is not uncommon, and its recurrence is
      often a challenging clinical problem. Surgical management and predisposing
      factors for the recurrence of PSP, however, have not yet been well elucidated in
      adolescent patients. The major aim of this study was to investigate factors
      associated with proceeding to surgical intervention and recurrence of PSP in
      adolescents. Two hundred and nineteen episodes of PSP in 171 adolescent patients
      were retrospectively reviewed. The clinical and radiological spectrum of PSP and
      factors for proceeding to surgical intervention were assessed in these 171
      patients. Risk factors for the recurrence of PSP were further analyzed in 128
      patients with first attack of PSP. The male-to-female ratio of the 171 PSP
      patients was 9:1, and the mean age was 17.6 +/- 1.5 years. The median body mass
      index (BMI) percentile was 11 (range 2-31), and 45 (34 %) patients had
      underweight BMI. The incidence of recurrent PSP was high with a total recurrence
      rate of 21 %. Ipsilateral recurrence rate of PSP after video-assisted
      thoracoscopic surgery (VATS) was much less than that of the conservative
      treatment (4 vs. 18 %). A large-size pneumothorax with a persistent air leak was
      the most significant factor for proceeding to VATS surgery (P = 0.001). In
      addition, it was a significant factor influencing the recurrence of PSP (P =
      0.014). Other factors that did not significantly affect the recurrence rate were
      BMI, smoking status, and the number of bullae. CONCLUSION: Adolescent PSP has a
      high recurrence rate of 21 % after a 2-year follow-up. A large-size pneumothorax
      with a persistent air leak may not only lead to surgical intervention but also
      the risk of a recurrence of PSP. The initial size of pneumothorax may not only
      guide the management process but also predict the risk of a recurrence in
      adolescent patients with PSP.

PMID- 24893953
TI  - Recovery of Pseudomonas aeruginosa culturability following copper- and chlorine
      induced stress.
AB  - This study investigated how quickly cells of the opportunistic pathogen
      Pseudomonas aeruginosa recover culturability after exposure to two of the most
      common environmental stressors present in drinking water, free chlorine and
      copper ions. Viable but nonculturable (VBNC) P. aeruginosa undetected by direct
      culturing following exposure to free chlorine or copper ions can survive in
      drinking water systems, with potential to recover, multiply, and regain
      infectivity. Cells were exposed to copper sulfate (0.25 mg Cu(2+)  L(-1) ) or
      free chlorine (initial dose of 2 mg Cl2  L(-1) ) for 24 h. Despite total loss of
      culturability and a reduction in viability from 1.2 * 10(7) to 4 * 10(3)  cells
      mL(-1) (3.5 log), cells exposed to chlorine recovered viability quickly after the
      depletion of free chlorine, while culturability was recovered within 24 h. Copper
      ions did not depress viability, but reduced culturability from 3 * 10(7) to 2.3 *
      10(2)  cells mL(-1) (5.1 log); VBNC cells regained culturability immediately
      after copper ion chelation. A comparison between direct culturing and Pseudalert,
      a specific enzyme-based assay, was performed. Both detection methods were well
      correlated in the range of 10(2) -10(10)  cells L(-1) . However, correlations
      between the methods declined after exposure to copper ions. 

PMID- 24893952
TI  - Lipid metabolism enzyme ACSVL3 supports glioblastoma stem cell maintenance and
      tumorigenicity.
AB  - BACKGROUND: Targeting cell metabolism offers promising opportunities for the
      development of drugs to treat cancer. We previously found that the fatty acyl-CoA
      synthetase VL3 (ACSVL3) is elevated in malignant brain tumor tissues and involved
      in tumorigenesis. This study investigates the role of ACSVL3 in the maintenance
      of glioblastoma multiforme (GBM) stem cell self-renewal and the capacity of GBM
      stem cells to initiate tumor xenograft formation. METHODS: We examined ACSVL3
      expression during differentiation of several GBM stem cell enriched neurosphere
      cultures. To study the function of ACSVL3, we performed loss-of-function by using
      small interfering RNAs to target ACSVL3 and examined stem cell marker expression,
      neurosphere formation and tumor initiation properties. RESULTS: ACSVL3 expression
      levels were substantially increased in GBM stem cell enriched neurosphere
      cultures and decreased after differentiation of the neurospheres. Down-regulating
      ACSVL3 with small inhibiting RNAs decreased the expression of markers and
      regulators associated with stem cell self-renewal, including CD133, ALDH, Musashi
      1 and Sox-2. ACSVL3 knockdown in neurosphere cells led to increased expression of
      differentiation markers GFAP and Tuj1. Furthermore, ACSVL3 knockdown reduced
      anchorage-independent neurosphere cell growth, neurosphere-forming capacity as
      well as self-renewal of these GBM stem cell enriched neurosphere cultures. In
      vivo studies revealed that ACSVL3 loss-of-function substantially inhibited the
      ability of neurosphere cells to propagate orthotopic tumor xenografts. A link
      between ACSVL3 and cancer stem cell phenotype was further established by the
      findings that ACSVL3 expression was regulated by receptor tyrosine kinase
      pathways that support GBM stem cell self-renewal and tumor initiation, including
      EGFR and HGF/c-Met pathways. CONCLUSIONS: Our findings indicate that the lipid
      metabolism enzyme ACSVL3 is involved in GBM stem cell maintenance and the tumor
      initiating capacity of GBM stem cell enriched-neurospheres in animals.

PMID- 24893951
TI  - Mechanism of drug-induced gingival overgrowth revisited: a unifying hypothesis.
AB  - Drug-induced gingival overgrowth (DIGO) is a disfiguring side effect of anti
      convulsants, calcineurin inhibitors, and calcium channel blocking agents. A
      unifying hypothesis has been constructed which begins with cation flux inhibition
      induced by all three of these drug categories. Decreased cation influx of folic
      acid active transport within gingival fibroblasts leads to decreased cellular
      folate uptake, which in turn leads to changes in matrix metalloproteinases
      metabolism and the failure to activate collagenase. Decreased availability of
      activated collagenase results in decreased degradation of accumulated connective
      tissue which presents as DIGO. Studies supporting this hypothesis are discussed. 

PMID- 24893954
TI  - Mild cognitive impairment diagnosed with the new DSM-5 criteria: prevalence and
      associations with non-cognitive psychopathology.
AB  - OBJECTIVE: To contrast the prevalence of mild cognitive impairment (MCI) as
      diagnosed using DSM-5 criteria (DSM5-MCI) with MCI as diagnosed using Petersen's
      criteria (P-MCI) and to explore the association of both with non-cognitive
      psychopathological symptoms (NCPS). METHOD: A two-phase epidemiological screening
      was implemented in a population-based sample of individuals aged 55+ (n = 4803).
      The Geriatric Mental State (GMS) was the main psychopathological instrument used,
      and AGECAT was used to make psychiatric diagnoses. Research psychiatrists
      diagnosed DSM5-MCI and P-MCI using operational criteria. Logistic regression
      models were then used to investigate the association of MCI with anxiety and
      depression and with NCPS. RESULTS: Weighted prevalence of DSM5-MCI and P-MCI was,
      respectively, 3.72% and 7.93% for the aged 65+. NCPS were common in both MCI
      categories, but negative-type symptoms such as 'anergia' and 'observed slowness'
      were considerably more frequent among persons with DSM5-MCI. Anxiety and
      depression diagnostic categories were associated with both P-MCI and DSM5-MCI,
      but affective-type symptoms were mainly associated with P-MCI. Some negative-type
      symptoms were inversely associated with P-MCI, and no association was observed
      with DSM5-MCI. CONCLUSION: The prevalence of DSM5-MCI was half that of P-MCI.
      Negative-type NCPS were more frequently and typically associated with DSM5-MCI.

PMID- 24893955
TI  - Situational and mood factors associated with smoking in young adult light and
      heavy smokers.
AB  - INTRODUCTION AND AIMS: Antecedents of smoking have been widely researched in
      studies with older adults. However, less is known about the smoking patterns and
      antecedents of smoking in young adult smokers. DESIGN AND METHODS: In this study,
      we used ecological momentary assessment collected with an Internet-based survey
      instrument and used the participants' own mobile phones to contrast the smoking
      patterns of young adult light and intermittent smokers (n = 23) with heavy
      smokers (n = 18). Overall, 1543 smoking and non-smoking situations were analysed.
      By means of generalised estimating equations, we used a range of situational
      characteristics to predict smoking in both groups. RESULTS: Craving and smoking
      of others increased the odds of smoking, and smoking bans were associated with a
      decreased probability of smoking among both light and intermittent smokers and
      heavy smokers. Situational antecedents differed between both groups. Cue
      associated smoking played a bigger role for light and intermittent smokers than
      for heavy smokers. Situational antecedents, such as craving, being at the home of
      others, drinking alcohol and smoking by others, were more strongly associated
      with the smoking of light and intermittent smokers compared with heavy smokers.
      DISCUSSION AND CONCLUSIONS: Smoking among young adults is associated with both
      internal and external situational characteristics. Compared with heavy smokers,
      light and intermittent smoking seems to be under more stimulus control and more
      characterised by social smoking. These results are consistent with several
      findings from previous studies and provide further information on different
      subgroups of smokers in early adulthood.

PMID- 24893957
TI  - Future of whole genome sequencing.

PMID- 24893959
TI  - A study of interaction potentials for H2 adsorption in Single Walled Nano Tubes:
      a possible way to more realistic predictions.
AB  - A comparative analysis of interaction potentials, classified according to the
      parametrization method, namely Lorentz-Berthelot rules, semi-empirical or ab
      initio calculations, found their energy depths to scale, respectively, to ca 30K,
      ca 40K, and ca 60K. We draw the Potential Energy Surfaces (PESs) for a hydrogen
      probe molecule inside a Carbon Nano-Tube (CNT): it is shown that the adsorption
      energy increases with the hard radius of the interaction potential and decreases
      as the CNT pore enlarges. This is valid just for low-medium pressures, when
      hydrogen repulsions are negligible. If not, adsorption is driven by H2-H2 hard
      radius despite all other parameters. Monte Carlo (MC) simulations, following the
      Gibbs Ensemble (GE) in high density conditions, confirm that the thermodynamic
      equilibrium of an order-disorder phase transition show no changes throughout any
      of the studied potentials. We also analyse, in the Grand Canonical (GC) ensemble,
      the geometric and structural characteristics of square lattice bundles of Single
      Walled Nano Tubes (SWNTs) with regard to their influence on adsorption storage.
      To do so, we develop a method for independently simulate inner or outer
      adsorption in infinitely long nanotube lattice systems. Our results suggest a
      pressure range for convenient H2 storage and enlighten the influence of CNT size
      on adsorption performance. In addition, larger CNTs are capable to host further
      hydrogen layers, but only at very high pressures.

PMID- 24893956
TI  - The transcriptional response of apple alcohol acyltransferase (MdAAT2) to
      salicylic acid and ethylene is mediated through two apple MYB TFs in transgenic
      tobacco.
AB  - Volatile esters are major factors affecting the aroma of apple fruits, and
      alcohol acyltransferases (AATs) are key enzymes involved in the last steps of
      ester biosynthesis. The expression of apple AAT (MdAAT2) is known to be induced
      by salicylic acid (SA) or ethylene in apple fruits, although the mechanism of its
      transcriptional regulation remains elusive. In this study, we reveal that two
      apple transcription factors (TFs), MdMYB1 and MdMYB6, are involved in MdAAT2
      promoter response to SA and ethylene in transgenic tobacco. According to
      electrophoretic mobility shift assays, MdMYB1 or MdMYB6 can directly bind in
      vitro to MYB binding sites in the MdAAT2 promoter. In vivo, overexpression of the
      two MYB TFs can greatly enhance MdAAT2 promoter activity, as demonstrated by dual
      luciferase reporter assays in transgenic tobacco. In contrast to the promoter of
      MdMYB1 or MdMYB6, the MdAAT2 promoter cannot be induced by SA or ethephon (ETH)
      in transgenic tobacco, even in stigmas in which the MdAAT2 promoter can be highly
      induced under normal conditions. However, the induced MYB TFs can dramatically
      enhance MdAAT2 promoter activity under SA or ETH treatment. We conclude that
      MdMYB1 and MdMYB6 function in MdAAT2 responses to SA and ethylene in transgenic
      tobacco, suggesting that a similar regulation mechanism may exist in apple. 

PMID- 24893958
TI  - Citation searching: a systematic review case study of multiple risk behaviour
      interventions.
AB  - BACKGROUND: The value of citation searches as part of the systematic review
      process is currently unknown. While the major guides to conducting systematic
      reviews state that citation searching should be carried out in addition to
      searching bibliographic databases there are still few studies in the literature
      that support this view. Rather than using a predefined search strategy to
      retrieve studies, citation searching uses known relevant papers to identify
      further papers. METHODS: We describe a case study about the effectiveness of
      using the citation sources Google Scholar, Scopus, Web of Science and OVIDSP
      MEDLINE to identify records for inclusion in a systematic review.We used the 40
      included studies identified by traditional database searches from one systematic
      review of interventions for multiple risk behaviours. We searched for each of the
      included studies in the four citation sources to retrieve the details of all
      papers that have cited these studies.We carried out two analyses; the first was
      to examine the overlap between the four citation sources to identify which
      citation tool was the most useful; the second was to investigate whether the
      citation searches identified any relevant records in addition to those retrieved
      by the original database searches. RESULTS: The highest number of citations was
      retrieved from Google Scholar (1680), followed by Scopus (1173), then Web of
      Science (1095) and lastly OVIDSP (213). To retrieve all the records identified by
      the citation tracking searching all four resources was required. Google Scholar
      identified the highest number of unique citations.The citation tracking
      identified 9 studies that met the review's inclusion criteria. Eight of these had
      already been identified by the traditional databases searches and identified in
      the screening process while the ninth was not available in any of the databases
      when the original searches were carried out. It would, however, have been
      identified by two of the database search strategies if searches had been carried
      out later. CONCLUSIONS: Based on the results from this investigation, citation
      searching as a supplementary search method for systematic reviews may not be the
      best use of valuable time and resources. It would be useful to verify these
      findings in other reviews.

PMID- 24893960
TI  - Mechanistic exploration of the catalytic cycles for the CO oxidation by O2 over
      FeO(1-3) application of the energetic span model.
AB  - Carbon monoxide (CO) and oxygen (O2) catalyzed by small neutral iron oxide
      clusters (FeO(1-3)) was investigated at the density functional level of theory
      using the Becke-Perdew-Wang functional (BPW91). Three reaction pathways along
      with singlet, triplet and quintet states were calculated for ascertaining the
      presence of some spin inversion during the catalytic cycle. The catalytic cycle
      was found to be "two state reactivity" resulting from the crossing among the
      multistate energetic profiles. The Landau-Zener equation was used to calculate
      the thermally-averaged spin transition probabilities for the non-adiabatic
      surface crossing reaction. In order to predict the efficiency of catalyst the
      energetic span model developed by Kozuch was implemented, whereas this model is
      not suitable for handling the diabatic reaction, this feature we must take into
      consideration. To this end, a kinetic assessment is carried out with an expansion
      of the energetic span model, including the spin-crossing effects. This
      approximation enables one to measure the efficiency of catalytic cycle including
      spin-crossing effects by quantum mechanical computation.

PMID- 24893961
TI  - A hyaluronic acid-methotrexate conjugate for targeted therapy of rheumatoid
      arthritis.
AB  - In an effort to improve the therapeutic efficacy of methotrexate (MTX), we
      prepared the hyaluronic acid-MTX conjugate for targeted therapy of rheumatoid
      arthritis (RA). Owing to the pH-sensitive nature of the conjugate, MTX was
      rapidly released under the mildly acidic conditions, similar to the environment
      of inflamed synovial tissue in RA. 

PMID- 24893962
TI  - Decentralizing postabortion care in Senegal with misoprostol for incomplete
      abortion.
AB  - OBJECTIVE: To expand access to postabortion care (PAC) services in Senegal by
      introducing misoprostol as a first-line treatment at the community level.
      METHODS: The present prospective study enrolled 481 women seeking treatment for
      incomplete abortion at 11 community health posts in Senegal between September
      2011 and August 2012. Participants were given 400 MUg of sublingual misoprostol
      and asked to return to the clinic 1 week later to confirm clinical status. At
      study completion, all women were asked to respond to a series of questions
      regarding their experience with this method. All care was provided by nurse
      midwives. RESULTS: All but three of the study women (99.4%; 474/477) had
      successful complete abortion after taking misoprostol. Almost all women were
      satisfied or very satisfied with the treatment (99.6%; 469/471), would select the
      method again if needed (98.9%; 465/470), and would recommend the method to a
      friend (99.8%; 468/469). CONCLUSION: The results provide further evidence that
      400 MUg of misoprostol is highly effective for first-line treatment of incomplete
      abortion. Furthermore, this regimen can be fully provided by nurse midwives, and
      can be easily and successfully introduced in community health settings where
      other methods of PAC may not previously have been available. Clinicaltrials.gov:
      NCT01939457.

PMID- 24893964
TI  - Amide coupling reaction for the synthesis of bispyridine-based ligands and their
      complexation to platinum as dinuclear anticancer agents.
AB  - Amide coupling reactions can be used to synthesize bispyridine-based ligands for
      use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic
      acid, or its derivatives, are coupled to variable length diaminoalkane chains
      under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base,
      triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products
      precipitate from solution upon formation or can be precipitated by the addition
      of water. If desired, the ligands can be further purified by recrystallization
      from hot water. Dinuclear platinum complex synthesis using the bispyridine
      ligands is done in hot water using transplatin. The most informative of the
      chemical characterization techniques to determine the structure and gross purity
      of both the bispyridine ligands and the final platinum complexes is (1)H NMR with
      particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum
      complexes have potential application as anticancer agents and the synthesis
      method can be modified to produce trinuclear and other multinuclear complexes
      with different hydrogen bonding functionality in the bridging ligand. 

PMID- 24893963
TI  - Visualization of G3BP stress granules dynamics in live primary cells.
AB  - SGs can be visualized in cells by immunostaining of specific protein components
      or polyA+ mRNAs. SGs are highly dynamic and the study of their assembly and fate
      is important to understand the cellular response to stress. The deficiency in key
      factors of SGs like G3BP (RasGAP SH3 domain Binding Protein) leads to
      developmental defects in mice and alterations of the Central Nervous System. To
      study the dynamics of SGs in cells from an organism, one can culture primary
      cells and follow the localization of a transfected tagged component of SGs. We
      describe time-lapse experiment to observe G3BP1-containing SGs in Mouse Embryonic
      Fibroblasts (MEFs). This technique can also be used to study G3BP-containing SGs
      in live neurons, which is crucial as it was recently shown that these SGs are
      formed at the onset of neurodegenerative diseases like Alzheimer's disease. This
      approach can be adapted to any other cellular body and granule protein component,
      and performed with transgenic animals, allowing the live study of granules
      dynamics for example in the absence of a specific factor of these granules.

PMID- 24893965
TI  - Effect of chronic kidney disease on A1C in individuals being screened for
      diabetes.
AB  - OBJECTIVE: Glycated haemoglobin (A1C) has been recommended for the diagnosis of
      type 2 diabetes mellitus. Chronic kidney disease (CKD) is reported to increase
      A1C. The prevalence of CKD and its association with A1C as a diagnostic test for
      type 2 diabetes screening in a community population was studied. RESEARCH DESIGN
      AND METHODS: Age, gender, ethnicity (white/South Asian), haemoglobin, A1C,
      fasting glucose and fructosamine were compared in participants with estimated
      glomerular filtration rate (eGFR) 30-59 (CKD 3) and >=60 ml/min/1.73 m(2) using
      chi-squared or t-tests. Multivariable linear regression analyses were performed
      with A1C as the dependent variable; remaining variables were forced into a model
      to identify correlates with A1C. Data were parametric and expressed as means.
      RESULTS: Of 949 participants 83.7% had eGFR >=60, 16.3% had CKD 3 and only 2 had
      eGFR <30 (CKD >=4). Compared with eGFR >=60, patients with CKD 3 were older
      [p<0.001], had higher A1C [6.0% vs. 5.8%, p<0.001], fasting glucose [5.4 vs. 5.2m
      mol/L, p=0.003] and fructosamine [233.7 vs. 225.8MU mol/L, p<0.001] but lower
      haemoglobin [p=0.006]. After adjustment, gender and CKD stage were not associated
      with A1C. A1C was associated (p<0.05) positively with age, South Asian ethnicity,
      fasting glucose and fructosamine and inversely with haemoglobin levels.
      CONCLUSIONS: Severe CKD (stage >=4) is rare in primary care patients being
      screened for type 2 diabetes and its impact on A1C could not be evaluated.
      Although A1C is higher among patients with CKD stage 3 compared to those with
      eGFR >=60, this appeared to be due to the confounding effect of other variables
      rather than the presence of CKD.

PMID- 24893966
TI  - Chromium accumulation in the Asian clam, Corbicula fluminea (Muller, 1774), as an
      indicative of landfill leachate contamination.
AB  - The Asian clam Corbicula fluminea exposed in situ for periods of 1, 5, 15 and 30
      days along a stream which receives landfill leachate effluent showed increased Cr
      accumulation in gills and digestive gland, although Cr concentrations have been
      found to be low in sediment. Other metals such as Pb, Ni, Al and Cu were also
      analyzed but were found to accumulate in clam tissues in lower concentrations or
      without showing a consistent pattern. Thus, the accumulation of a single
      contaminant such as Cr is proposed to be used as a tool to assess exposure to a
      complex mixture such as landfill leachates.

PMID- 24893967
TI  - Magnetic resonance imaging in zirconia-based dental implantology.
AB  - OBJECTIVES: X-ray-based planning and post-implantation assessment of titanium
      implants is the commonly accepted standard to date. However, new implant
      materials such as zirconia (ZrO2 ) have become available, and magnetic resonance
      imaging may be a valuable alternative with these implants. The present in vitro
      study investigated artifacts produced by titanium and zirconia implants in
      magnetic resonance imaging (MRI) and assessed the accuracy of pre-implant
      planning and post-implantation assessment comparing MRI to standard X-ray-based
      imaging modalities: Orthopantomogram (OPT), cone beam (CBCT), and computed
      tomography (CT). MATERIALS AND METHODS: Twelve porcine mandibles were prepared
      and scanned (MRI, OPT, CBCT, MUCT), and bone height above the nerve canal was
      measured. Specimens were implanted with either two titanium or zirconia implants
      and rescanned to investigate the influence of implant materials on post
      implantation assessment. MRI and MUCT artifacts were quantified with implants
      embedded in gelatin phantoms and porcine specimens. RESULTS: Compared with CBCT
      set as standard, MUCT, OPT, and MRI showed similar accuracy in pre-op bone height
      measurements. Post-implantation, while titanium implants induced a strong B0 
      field distortion resulting in extensive signal voids, zirconia implants were
      clearly depictable with only minor distortions. CONCLUSIONS: Excellent contrast,
      limited artifacts, radiation-free and accurate implant assessment may indicate
      that MRI is a valuable imaging alternative for zirconia-based implant dentistry.

PMID- 24893968
TI  - Prone left-sided whole-breast irradiation: significant heart dose reduction using
      end-inspiratory versus end-expiratory gating.
AB  - PURPOSE: To quantify the influence on heart dose metrics of prone left-sided
      whole-breast irradiation in an end-inspiratory phase (PrIN) versus an end
      expiratory phase (PrEX). PATIENTS AND METHODS: Twenty patients underwent CT
      simulation in PrIN and PrEX. Dynamic intensity-modulated radiotherapy was planned
      for whole-breast irradiation with a median prescription dose of 40.05Gy in 15
      fractions and maximal sparing of the organs at risk. Dose-volume parameters were
      analyzed for heart, left anterior descending coronary artery, ipsilateral lung
      and both breasts. RESULTS: PrIN consistently reduced (P<0.001) heart and left
      anterior descending coronary artery dose metrics compared to PrEX. Population
      averages for maximum and mean heart dose were 6.2Gy and 1.3Gy for PrIN versus
      21.4Gy and 2.5Gy for PrEX, respectively. Moreover, a maximum heart dose less than
      10Gy was achieved in 80% of patients for PrIN. Target dose distribution,
      ipsilateral lung and contralateral breast sparing by radiation dose were similar
      for both procedures. CONCLUSIONS: Inspiratory gating consistently reduced heart
      dose metrics pointing to a possible benefit of breathing-adapted radiotherapy for
      prone left-sided whole-breast irradiation.

PMID- 24893969
TI  - Effectiveness of wearable defibrillators: systematic review and quality of
      evidence.
AB  - OBJECTIVES: The objectives of this systematic literature review were to identify
      all published literature on wearable defibrillators, assess the wearable
      defibrillator's efficacy and effectiveness in general and among specific patient
      groups, including post-myocardial infarction, post coronary artery bypass
      grafting or percutaneous coronary intervention, non-ischemic cardiomyopathy, and
      ischemic cardiomyopathy, and to evaluate the quality of evidence. METHODS: The
      search and synthesis was informed by the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses statement, and the quality of evidence was evaluated
      using the Grading of Recommendations Assessment, Development and Evaluation and
      the Newcastle Ottawa Scale. RESULTS: A total of thirty-six articles and
      conference abstracts from thirty-three studies were included in the review. It
      appears that wearable defibrillator use compared with no defibrillator use
      reduces the chance of ventricular tachycardia and ventricular fibrillation
      (VT/VF) associated deaths by an absolute risk reduction of approximately 1
      percent, achieved by averting approximately 4/5th of all VT/VF associated deaths.
      The quality of evidence was low to very low quality, such that our confidence in
      the reported estimates is weak. CONCLUSIONS: To validate beneficial results,
      further investigation using robust study designs conducted by independent
      researchers is warranted.

PMID- 24893970
TI  - Costs for stroke in Sweden 2009 and developments since 1997.
AB  - OBJECTIVES: The aim of this study was to estimate direct and indirect excess
      costs attributable to stroke in Sweden in 2009 and to compare these with similar
      estimates from 1997. METHODS: Data on first-ever stoke admissions in the first
      half of 2009 from the Swedish national stroke register (RS) were used for cost
      calculations and compared with results from 1997 also using RS data. A societal
      perspective was taken including the acute and follow-up phase, rehabilitation,
      stroke re-admissions, drugs, home- and residential care services for activities
      of daily life (ADL) support, and indirect costs for premature death and
      productivity losses (2009 prices). Survival was extrapolated to estimate the
      lifetime present value cost of stroke. RESULTS: The societal lifetime present
      value cost for stroke in 2009 was ?68,800 per patient (ADL support: 59 percent;
      productivity losses: 21 percent). Women had higher costs than men in all age
      groups as a result from greater need for ADL support. Patients treated at a
      stroke unit indicated low incremental cost per life-year gained compared with
      those who had not. The total lifetime cost increased between 1997 and 2009.
      Hospitalization costs per patient were stable, while long-term costs for home-
      and residential care services increased. CONCLUSIONS: Changes in patient
      characteristics, longer expected survival, and possibly in the Swedish stroke
      care, have led to higher annual and lifetime costs per patient in 2009 compared
      with 1997. A comprehensive national stroke care performance register like RS may
      be suitable for health economic assessments.

PMID- 24893971
TI  - Burden of decompensated cirrhosis and ascites on hospital services in a tertiary
      care facility: time for change?
AB  - BACKGROUND: Ascites, the most frequent complication of cirrhosis, is associated
      with poor prognosis and reduced quality of life. Recurrent hospital admissions
      are common and often unplanned, resulting in increased use of hospital services.
      AIMS: To examine use of hospital services by patients with cirrhosis and ascites
      requiring paracentesis, and to investigate factors associated with early
      unplanned readmission. METHODS: A retrospective review of the medical chart and
      clinical databases was performed for patients who underwent paracentesis between
      October 2011 and October 2012. Clinical parameters at index admission were
      compared between patients with and without early unplanned hospital readmissions.
      RESULTS: The 41 patients requiring paracentesis had 127 hospital admissions, 1164
      occupied bed days and 733 medical imaging services. Most admissions (80.3%) were
      for management of ascites, of which 41.2% were unplanned. Of those eligible,
      69.7% were readmitted and 42.4% had an early unplanned readmission. Twelve
      patients died and nine developed spontaneous bacterial peritonitis. Of those
      eligible for readmission, more patients died (P = 0.008) and/or developed
      spontaneous bacterial peritonitis (P = 0.027) if they had an early unplanned
      readmission during the study period. Markers of liver disease, as well as
      haemoglobin (P = 0.029), haematocrit (P = 0.024) and previous heavy alcohol use
      (P = 0.021) at index admission, were associated with early unplanned readmission.
      CONCLUSION: Patients with cirrhosis and ascites comprise a small population who
      account for substantial use of hospital services. Markers of disease severity may
      identify patients at increased risk of early readmission. Alternative models of
      care should be considered to reduce unplanned hospital admissions, healthcare
      costs and pressure on emergency services.

PMID- 24893972
TI  - Tumours of the lacrimal gland. Epidemiological, clinical and genetic
      characteristics.
AB  - Tumours of the lacrimal gland are rare, but the prognosis may be grave. To date,
      no population-based incidence and distribution data on lacrimal gland tumours
      exist. In addition, almost nothing is known about the genetic profile of
      epithelial tumours of the lacrimal gland. We collected specimens and clinical
      files on all biopsied lacrimal gland lesions in Denmark over a 34-year period and
      re-evaluated the diagnosis to provide updated population-based incidence rates
      and epidemiological characteristics. Clinical data regarding symptoms, clinical
      examinations, treatment and follow-up were collected for patients with adenoid
      cystic carcinoma (ACC), pleomorphic adenoma (PA), carcinoma ex pleomorphic
      adenoma (Ca-ex-PA) and mucoepidermoid carcinoma (MEC). Using RT-PCR, FISH,
      immunohistochemistry, Q-PCR and high-resolution array-based comparative genomic
      hybridization (arrayCGH) we explored the genetic characteristics including copy
      number alterations (CNA) in ACC, PA, Ca-ex-PA and MEC. The incidence of biopsied
      lacrimal gland lesions was 1.3/1,000,000/year, and ~50% were neoplastic lesions.
      Of these, 55% were malignant tumours with epithelial tumours as the most
      frequent. The overall incidence was increasing, and this was caused by an
      increase in biopsied non-neoplastic lesions. We found that 10/14 ACCs either
      expressed the MYB-NFIB fusion gene and/or had rearrangements of MYB. All ACCs
      expressed the MYB protein. ACC was characterized by recurrent copy number losses
      involving 6q, 12q and 17q and gains involving 19q, 8q and 11q. ArrayCGH revealed
      an apparently normal genomic profile in 11/19 PAs. The remaining 8 PAs had
      recurrent copy number losses involving 1p, 6q, 8q and 13q and gain involving 9p.
      PA expressed PLAG1 in all tumours whereas only 2/29 tumours expressed HMGA2. Ca
      ex-PA was characterized by recurrent copy number gain involving 22q. PLAG1 was
      expressed in 3/5 Ca-ex-PA whereas none of these tumours expressed HMGA2. MEC
      expressed the CRTC1-MAML2, and this fusion was found to be tumour-specific for
      lacrimal gland MEC. In conclusion, lacrimal gland lesions that require
      pathological evaluation are rare in the Danish population, and the incidence rate
      of biopsied benign lesions is increasing. Epithelial tumours of the lacrimal
      gland are molecularly very similar to their salivary gland counterparts in the
      expression of the tumour-specific fusion genes and in their genomic imbalances as
      demonstrated by arrayCGH. MYB-NFIB is a useful biomarker for ACC and MYB, and its
      downstream target genes may be potential therapeutic targets for these tumours.

PMID- 24893974
TI  - Linking a short-stature specific health-related quality of life measure (QoLISSY)
      to the International Classification of Functioning - Children and Youth (ICF-CY).
AB  - PURPOSE: The study aimed to examine and compare the content of the quality of
      life in short-stature youth questionnaire (QoLISSY) with the International
      Classification of Functioning, Disability and Health - Children and Youth (ICF
      CY). METHODS: Items of the QoLISSY questionnaire for children/adolescents and
      their parents were coded within the framework of the ICF-CY. Linkage was
      performed according to predetermined standards by two health professionals
      experienced in the conceptual fundaments of the ICF-CY. RESULTS: Within the
      linking process 58 meaningful concepts were identified from the 55 items out of
      the QoLISSY parent questionnaire and 55 meaningful concepts from the 50 items of
      the QoLISSY (children) questionnaire. In total, 57 concepts (parent
      questionnaire) and 54 concepts (children-questionnaire) were linked to the
      different categories of the ICF-CY. Twenty-seven categories (parents-version) and
      20 categories (child-version) referred to the component body functions, 34
      categories (parent-version) and 30 categories (child-version) represented the
      activity and participation component and in each version 30 categories
      represented the environmental factors component. CONCLUSIONS: The present study
      indicates that the ICF-CY provides a useful frame of reference to compare and
      examine the content of HrQoL instruments for short-statured children and
      adolescents and their parents. The linkage of the QoLISSY instrument within the
      framework of the ICF-CY translates its content into a universal language.

PMID- 24893973
TI  - Altered microglial response to Abeta plaques in APPPS1-21 mice heterozygous for
      TREM2.
AB  - BACKGROUND: Recent genome-wide association studies linked variants in TREM2 to a
      strong increase in the odds of developing Alzheimer's disease. The mechanism by
      which TREM2 influences the susceptibility to Alzheimer's disease is currently
      unknown. TREM2 is expressed by microglia and is thought to regulate phagocytic
      and inflammatory microglial responses to brain pathology. Given that a single
      allele of variant TREM2, likely resulting in a loss of function, conferred an
      increased risk of developing Alzheimer's disease, we tested whether loss of one
      functional trem2 allele would affect Abeta plaque deposition or the microglial
      response to Abeta pathology in APPPS1-21 mice. RESULTS: There was no significant
      difference in Abeta deposition in 3-month old or 7-month old APPPS1-21 mice
      expressing one or two copies of trem2. However, 3-month old mice with one copy of
      trem2 exhibited a marked decrease in the number and size of plaque-associated
      microglia. While there were no statistically significant differences in cytokine
      levels or markers of microglial activation in 3- or 7-month old animals, there
      were trends towards decreased expression of NOS2, C1qa, and IL1a in 3-month old
      TREM2+/- vs. TREM2+/+ mice. CONCLUSIONS: Loss of a single copy of trem2 had no
      effect on Abeta pathology, but altered the morphological phenotype of plaque
      associated microglia. These data suggest that TREM2 is important for the
      microglial response to Abeta deposition but that a 50% decrease inTREM2
      expression does not affect Abeta plaque burden.

PMID- 24893975
TI  - Returning to work - a long-term process reaching beyond the time frames of
      multimodal non-specific back pain rehabilitation.
AB  - PURPOSE: To explore and describe health professionals' experience of working with
      return to work (RTW) in multimodal rehabilitation for people with non-specific
      back pain. METHOD: An interview study using qualitative content analysis. Fifteen
      participants were interviewed, all were working with multimodal rehabilitation
      for people with non-specific back pain in eight different rehabilitation units.
      RESULTS: The participants experienced RTW as a long-term process reaching beyond
      the time frames of the multimodal rehabilitation (MMR). Their attitudes and,
      their patients' condition, impacted on their work which focused on psychological
      and physical well-being as well as participation in everyday life. They often
      created an action plan for the RTW process, however the responsibility for its
      realisation was transferred to other actors. The participants described limited
      interventions in connection with patients' workplaces. CONCLUSIONS: Recommended
      support in the RTW process in MMR comprises the provision of continuous
      supervision of vocational issues for the health care professionals, the
      development of guidelines and a checklist for how to work in close collaboration
      with patients' workplaces and employers, the provision of long-term follow-up in
      relation to the patients' work, and the development of proper interventions in
      order to promote transitions between all the different actors involved.
      IMPLICATIONS FOR REHABILITATION: Rehabilitation programs targeting return to work
      (RTW) for people with non-specific back pain needs to include features concretely
      focusing on vocational issues. Health and RTW is often seen as a linear process
      in which health comes before RTW. Rehabilitation programs could be tailored to
      better address the reciprocal relationship between health and work, in which they
      are interconnected and affect each other. The RTW process is reaching beyond the
      time frames of the multimodal rehabilitation but further support from the
      patients are asked for. The rehabilitation programs needs to be designed to
      provide long-term follow-up in relation to the patients' work.

PMID- 24893976
TI  - One-step, ultrasensitive, and electrochemical assay of microRNAs based on T7
      exonuclease assisted cyclic enzymatic amplification.
AB  - Taking advantage of the special exodeoxyribonuclease activity of T7 exonuclease,
      a simple, sensitive, selective, and label-free microRNA biosensor based on the
      cyclic enzymatic amplification method (CEAM) has been proposed. First, thiol
      functionalized DNA probes were assembled onto a gold nanoparticles modified gold
      electrode surface through a Au-S bond, followed by hybridizing with target miRNA.
      Subsequently, DNA in RNA/DNA duplexes was digested by T7 exonuclease, which can
      release the microRNA molecules from the electrode surface and return into the
      buffer solution. Meanwhile, the released microRNA can further hybridize with the
      unhybridized DNA probes on the modified electrode surface. On the basis of it, an
      isothermal amplification cycle is realized. The T7 exonuclease-assisted CEAM
      achieved a low detection limit of 0.17 fM. Moreover, this assay presents
      excellent specificity with discriminating only a single-base mismatched microRNA
      sequence. Furthermore, this work can also be applied to detect avian leukemia
      based on the decreased expression level of microRNA-21. 

PMID- 24893977
TI  - Inducing myointimal hyperplasia versus atherosclerosis in mice: an introduction
      of two valid models.
AB  - Various in vivo laboratory rodent models for the induction of artery stenosis
      have been established to mimic diseases that include arterial plaque formation
      and stenosis, as observed for example in ischemic heart disease. Two highly
      reproducible mouse models - both resulting in artery stenosis but each underlying
      a different pathway of development - are introduced here. The models represent
      the two most common causes of artery stenosis; namely one mouse model for each
      myointimal hyperplasia, and atherosclerosis are shown. To induce myointimal
      hyperplasia, a balloon catheter injury of the abdominal aorta is performed. For
      the development of atherosclerotic plaque, the ApoE -/- mouse model in
      combination with western fatty diet is used. Different model-adapted options for
      the measurement and evaluation of the results are named and described in this
      manuscript. The introduction and comparison of these two models provides
      information for scientists to choose the appropriate artery stenosis model in
      accordance to the scientific question asked.

PMID- 24893978
TI  - The incidence and implications of cerebral palsy following potentially avoidable
      obstetric complications: a preliminary burden of disease study.
AB  - OBJECTIVE: To determine the extent of cerebral palsy attributable to adverse
      obstetric events, and estimate the lifetime mortality and morbidity expectations
      of these individuals relative to age-matched members of the UK general
      population. DESIGN: Simulation model. SETTING UK POPULATION: All projected live
      births during 2014. METHODS: Using published data regarding the incidence and
      aetiology of cerebral palsy, we simulated the outcomes of a hypothetical cohort
      of UK live births. Survival and quality of life (QoL) for those with cerebral
      palsy were compared with age-matched individuals representative of the UK general
      population, in order to estimate the number of quality-adjusted life years
      (QALYs) lost following asphyxia-related cerebral palsy. MAIN OUTCOME MEASURES:
      Incidence of asphyxia-related cerebral palsy, QALYS, QoL, and survival. RESULTS:
      A total of 207 (95% CI 169-245) cases of asphyxia-related cerebral palsy were
      projected amongst UK children born during the year 2014, with approximately 15.2
      QALYs lost per case. If these results held true in a real birth cohort, 3142 (95%
      CI 2321-3963) QALYs would be lost as a consequence of asphyxia-related cerebral
      palsy, a loss valued by the UK National Health Service at L62.9 m (95% CI L46.4
      79.3 m). CONCLUSIONS: Cerebral palsy following intrapartum asphyxiation leads to
      significant reductions in QoL and survival; however, this may often be prevented.
      For those with GMFCS 1 and GMFCS 2 cerebral palsy (Gross Motor Function
      Classification System), lifetime QALYs accrued largely resemble those experienced
      by the UK general population, whereas for GMFCS 3 and GMFCS 4 QALYs are reduced
      considerably, and are negative in the case of GMFCS 5.

PMID- 24893979
TI  - A test of the DSM-5 severity scale for alcohol use disorder.
AB  - BACKGROUND: For the DSM-5-defined alcohol use disorder (AUD) diagnosis, a tri
      categorized scale that designates mild, moderate, and severe AUD was selected
      over a fully dimensional scale to represent AUD severity. The purpose of this
      study was to test whether the DSM-5-defined AUD severity measure was as
      proficient a predictor of alcohol use following a brief intervention, compared to
      a fully dimensional scale. METHODS: Heavy drinking primary care patients (N=246)
      received a physician-delivered brief intervention (BI), and then reported daily
      alcohol consumption for six months using an Interactive Voice Response (IVR)
      system. The dimensional AUD measure we constructed was a summation of all AUD
      criteria met at baseline (mean=6.5; SD=2.5). A multi-model inference technique
      was used to determine whether the DSM-5 tri-categorized severity measure or a
      dimensional approach would provide a more precise prediction of change in weekly
      alcohol consumption following a BI. RESULTS: The Akaike information criterion
      (AIC) for the dimensional AUD model (AIC=7623.88) was four points lower than the
      tri-categorized model (AIC=7627.88) and weight of evidence calculations indicated
      there was 88% likelihood the dimensional model was the better approximating
      model. The dimensional model significantly predicted change in alcohol
      consumption (p=.04) whereas the DSM-5 tri-categorized model did not. CONCLUSION:
      A dimensional AUD measure was superior, detecting treatment effects that were not
      apparent with tri-categorized severity model as defined by the DSM-5. We
      recommend using a dimensional measure for determining AUD severity.

PMID- 24893980
TI  - The current state and future prospects of chronic hepatitis C virus infection
      treatment.
AB  - Hepatitis C virus (HCV) infection is a significant cause of chronic liver disease
      with substantial long-term sequelae. Until very recently, therapies to cure HCV
      were hindered by high nonresponse rates and severe side effects. The first
      generation protease inhibitor-containing regimens provided superior cure rates
      for many HCV-infected patients, although their side-effect profile proved to be
      quite burdensome. We are now witnessing the emergence of therapies with superior
      cure rates, limited side effects, and broad genotypic activity. Two therapies,
      sofosbuvir (an NS5b polymerase inhibitor) and simeprevir (a second-generation
      NS3/4A protease inhibitor), were approved by the Food and Drug Administration in
      late 2013 for use in a number of HCV populations. This review focuses primarily
      upon these therapies and the key studies that support their use in practice.
      Furthermore, representative novel antiviral therapies, in advanced stages of
      testing, are also reviewed. 

PMID- 24893981
TI  - Clostridium difficile Infection (CDI) in Solid Organ and Hematopoietic Stem Cell
      Transplant Recipients.
AB  - Patients undergoing solid organ and stem cell transplantation are at increased
      risk of Clostridium difficile infection (CDI) compared with nontransplant
      patients. CDI may be associated with significant morbidity in this population
      including prolonged hospitalization, increased hospital charges, and
      complications in the transplanted organ. A combination of host factors, including
      both B-cell and T-cell immunosuppression, in addition to traditional risk factors
      for CDI such as broad-spectrum antibacterial exposure, are likely to contribute
      to the elevated risk in this population. This article addresses the current
      epidemiology and risk factors for CDI in transplant recipients, the downstream
      complications following this infection, and current management strategies, with
      an emphasis on novel approaches for primary and recurrent disease including fecal
      microbiota transplantation. 

PMID- 24893982
TI  - Update on fungal diagnostics.
AB  - Invasive fungal disease (IFD) is becoming more prevalent in transplant and
      oncology patients as a result of the potent immunosuppressive therapies used to
      prevent allograft rejection and/or the use of cytotoxic chemotherapy to treat
      cancer. Mortality attributable to IFD remains high despite advances in antifungal
      therapies. There is a continued need for laboratory diagnostics to help improve
      clinical outcomes. In recent years, culture-based detection strategies and
      histopathology have been supplemented with molecular and proteomic techniques as
      well as antigen detection methods. Refinements in these assays are improving the
      diagnosis of IFD, with the greatest strides made within the molecular and
      proteomic arenas. This review highlights recent laboratory developments in the
      diagnosis of invasive candidiasis, cryptococcosis, opportunistic molds, and
      endemic fungal infections. 

PMID- 24893983
TI  - Evaluation of dental morphometrics during the orthodontic treatment.
AB  - BACKGROUND: Diagnostic orthodontic and prosthetic procedures commence with an
      initial examination, during which a number of individual findings on occlusion or
      malocclusion are clarified. Nowadays we try to replace standard plaster casts by
      scanned objects and digital models. METHOD: Geometrically calibrated images aid
      in the comparison of several different steps of the treatment and show the
      variation of selected features belonging to individual biomedical objects. The
      methods used are based on geometric morphometrics, making a new approach to the
      evaluation of the variability of features. The study presents two different
      methods of measurement and shows their accuracy and reliability. RESULTS: The
      experimental part of the present paper is devoted to the analysis of the dental
      arch objects of 24 patients before and after the treatment using the distances
      between the canines and premolars as the features important for diagnostic
      purposes. Our work proved the advantage of measuring digitalized orthodontic
      models over manual measuring of plaster casts, with statistically significant
      results and accuracy sufficient for dental practice. CONCLUSION: A new method of
      computer imaging and measurements of a dental stone cast provides information
      with the precision required for orthodontic treatment. The results obtained point
      to the reduction in the variance of the distances between the premolars and
      canines during the treatment, with a regression coefficient RC=0.7 and confidence
      intervals close enough for dental practice. The ratio of these distances pointed
      to the nearly constant value of this measure close to 0.84 for the given set of
      24 individuals.

PMID- 24893984
TI  - Potassium 2-(1-hydroxypentyl)-benzoate improves memory deficits and attenuates
      amyloid and tau pathologies in a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterized by amyloid-beta (Abeta) deposition and neurofibrillary tangles. Dl
      PHPB [potassium 2-(1-hydroxypentyl)-benzoate], has been shown to have
      neuroprotective effects on cerebral ischemic, vascular dementia, and Abeta
      induced animal models by inhibiting oxidative injury, neuronal apoptosis, and
      glial activation. The aim of the present study was to examine the effect of dl
      PHPB on learning and memory in amyloid precursor protein (APP) and presenilin 1
      (PS1) double-transgenic AD mouse models (APP/PS1) and the mechanisms of dl-PHPB
      in reducing Abeta accumulation and tau phosphorylation. Twelve-month-old APP/PS1
      mice were given 30 mg/kg dl-PHPB by oral gavage for 3 months. Dl-PHPB treatment
      significantly improved the spatial learning and memory deficits compared with the
      vehicle-treated APP/PS1 mice. In the meantime, dl-PHPB obviously reduced tau
      hyperphosphorylation at Ser199, Thr205, and Ser396 sites in APP/PS1 mice. This
      reduction was accompanied by APP phosphorylation reduction and protein kinase C
      activation. In addition, expression of cyclin-dependent kinase and glycogen
      synthase kinase 3beta, the most important kinases involved in tau
      phosphorylation, was markedly decreased by dl-PHPB treatment. Phosphorylated
      protein kinase B and phosphoinositide 3-kinase levels of APP/PS1 mice were
      significantly reduced compared with levels in wild-type mice, and dl-PHPB
      reversed the reduction. The effects of dl-PHPB effecting a decrease in tau
      phosphorylation and kinase activation were further confirmed in neuroblastoma SK
      N-SH cells overexpressing wild-type human APP695. These data raised the
      possibility that dl-PHPB might be a promising multitarget neuronal protective
      agent for the treatment of AD. 

PMID- 24893986
TI  - Inhibitory effect of baicalin on collagen-induced arthritis in rats through the
      nuclear factor-kappaB pathway.
AB  - This study focused on the potential therapeutic effect of baicalin on collagen
      induced arthritis (CIA) in rats and the underlying mechanisms. The CIA rats were
      injected with baicalin (50, 100, or 200 mg/kg) once daily for 30 days. The rats
      were monitored for clinical severity of arthritis, and joint tissues were used
      for radiographic assessment and histologic examination. We quantified tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in
      experimental animals and used Western blots to assess levels of protein
      abundance, phosphorylation, and acetylation of nuclear factor (NF)-kappaB p65 and
      sirtuin 1 (sirt1) protein expression in joint tissues. Human fibroblast-like
      synoviocytes from rheumatoid arthritis (HFLS-RA) were adopted in further
      mechanistic investigations. Baicalin intraperitoneal injection for 30 days dose
      dependently blocked clinical manifestations of CIA, such as functional impairment
      and swollen red paws. Meanwhile, it alleviated collagen-induced joint
      inflammation injury and inhibited the secretion of TNF-alpha and IL-1beta in both
      rat synovium and HFLS-RA. Further mechanistic investigations revealed that
      baicalin suppresses NF-kappaB p65 protein expression and phosphorylation in
      synovial tissue and human-derived synoviocytes. Moreover, the acetylation of NF
      kappaB p65 was downregulated by baicalin, which negatively correlates with the
      baicalin-induced upregulation of sirt1 expression in the same conditions. The
      data indicate that CIA in rats can be alleviated by baicalin treatment via
      relieving joint inflammation, which is related to the suppression of synovial NF
      kappaB p65 protein expression and the elevation of its deacetylation by sirt1. 

PMID- 24893985
TI  - Novel synthetic toll-like receptor 4/MD2 ligands attenuate sterile inflammation.
AB  - Toll-like receptor (TLR) stimulation has been implicated as a major contributor
      to chronic inflammation. Among these receptors, TLR4 has been described as a key
      regulator of endogenous inflammation and has been proposed as a therapeutic
      target. Previously, we discovered by high-throughput screening a group of
      substituted pyrimido[5,4-b]indoles that activated a nuclear factor-kappaB
      reporter in THP-1 human monocytic cells. A biologically active hit compound was
      resynthesized, and derivatives were prepared to assess structure-activity
      relationships. The derived compounds activated cells in a TLR4/myeloid
      differentiation protein 2 (MD2)-dependent and CD14-independent manner, using the
      myeloid differentiation primary response 88 and Toll/IL-1 receptor domain
      containing adapter-inducing interferon-beta pathways. Two lead compounds, 1Z105
      and 1Z88, were selected for further analysis based on favorable biologic
      properties and lack of toxicity. In vivo pharmacokinetics indicated that 1Z105
      was orally bioavailable, whereas 1Z88 was not. Oral or parenteral doses of 1Z105
      and 1Z88 induced undetectable or negligible levels of circulating cytokines and
      did not induce hepatotoxicity when administered to galactosamine-conditioned
      mice, indicating good safety profiles. Both compounds were very effective in
      preventing lethal liver damage in lipopolysaccharide treated galatosamine
      conditioned mice. Orally administered 1Z105 and parenteral 1Z88 prevented
      arthritis in an autoantibody-driven murine model. Hence, these low molecular
      weight molecules that target TLR4/MD2 were well tolerated and effective in
      reducing target organ damage in two different mouse models of sterile
      inflammation. 

PMID- 24893987
TI  - Mouse monoclonal antibodies to transient receptor potential ankyrin 1 act as
      antagonists of multiple modes of channel activation.
AB  - The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in
      different pathophysiologies that include asthma, cough, itch, and inflammatory
      pain. Agonists of TRPA1 such as mustard oil and its key component allyl
      isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and pain
      behaviors in rodents. Hence, TRPA1 antagonists are being pursued as potential
      therapeutics. With the goal of generating monoclonal antibodies (mAbs) to human
      TRPA1 that could act as selective antagonists, we immunized mice with a variety
      of antigens expressing TRPA1 channels. After generation of hybridomas, the
      hybridoma conditioned media were screened to identify the mAbs that bind TRPA1
      channels by a flow cytometry assay utilizing U2OS or Chinese hamster ovary (CHO)
      cells stably expressing TRPA1. The purified IgGs from the hybridomas that showed
      selective binding to TRPA1 were evaluated for antagonism in agonist-induced
      (45)Ca(2+) uptake assays using CHO-TRPA1 cells. Several of the mAbs showed
      concentration-dependent inhibition of AITC and cold (4 degrees C) activation of
      TRPA1. The most potent mAb, 2B10, had IC50 values of approximately 260 and 90 nM
      in the two assays, respectively. These antagonist mAbs also blocked osmotically
      activated TRPA1 as well as activation by an endogenous agonist (4-oxo-2-nonenal).
      In summary, we generated mouse mAbs against TRPA1 that act as antagonists of
      multiple modes of TRPA1 activation. 

PMID- 24893988
TI  - Physicochemical, pasting, and functional properties of amaranth seed flours:
      effects of lipids removal.
AB  - The present work was carried out to evaluate physicochemical (composition, hunter
      color, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]),
      pasting, and functional properties (foaming, emulsification, water, and fat
      absorption capacity) of amaranth full-fat flours from 6 lines/cultivars (AFs),
      and to see the effects of lipid removal/defatting on these properties. Protein,
      ash, and lipid content of AFs ranged between 12.5% to 15.2%, 3.0% to 3.5%, and
      7.1% to 8.0%, respectively. The flours showed a number of bands between 97 and 7
      kDa, with main subunits of approximately 58, 37, 33, 31, 23, and 16 kDa in the
      SDS-PAGE profiles. The protein content and L* value increased, while b* values
      decreased following defatting for most of the lines/cultivars. The defatted
      flours (DAFs) had higher final viscosity and stability (lower breakdown
      viscosity) as compared to counterpart AFs. The protein profiling of the flours
      was not affected with the lipid removal/defatting. However, water absorption
      capacity and foam stability of the flours improved upon defatting. Principal
      component analysis revealed that pasting temperature was positively related to
      lipid content, while breakdown viscosity was negatively related to protein
      content. Foaming properties (capacity and stability) showed negative relationship
      with lipid content, and positive with protein content, ash content, water, and
      fat absorption capacity. PRACTICAL APPLICATION: Amaranth grains are known to have
      higher amount of proteins and lipids than cereals. Amaranth lipids are rich in
      unsaturated fatty acids, which are prone to oxidative rancidity. Removal of
      lipids or defatting of flours may be carried out to enhance product shelf life by
      preventing undesirable oxidative chain reactions. Therefore, this research was
      undertaken to see the effects of defatting on the functional properties of
      amaranth flours. The defatting was a value addition process as it improved the
      functional properties of the flours.

PMID- 24893991
TI  - Periodontitis-activated monocytes/macrophages cause aortic inflammation.
AB  - A relationship between periodontal disease and atherosclerosis has been suggested
      by epidemiological studies. Ligature-induced experimental periodontitis is an
      adequate model for clinical periodontitis, which starts from plaque accumulation,
      followed by inflammation in the periodontal tissue. Here we have demonstrated
      using a ligature-induced periodontitis model that periodontitis activates
      monocytes/macrophages, which subsequently circulate in the blood and adhere to
      vascular endothelial cells without altering the serum TNF-alpha concentration.
      Adherent monocytes/macrophages induced NF-kappaB activation and VCAM-1 expression
      in the endothelium and increased the expression of the TNF-alpha signaling
      cascade in the aorta. Peripheral blood-derived mononuclear cells from rats with
      experimental periodontitis showed enhanced adhesion and increased NF-kappaB/VCAM
      1 in cultured vascular endothelial cells. Our results suggest that periodontitis
      triggers the initial pathogenesis of atherosclerosis, inflammation of the
      vasculature, through activating monocytes/macrophages. 

PMID- 24893993
TI  - AGGF1 protects from myocardial ischemia/reperfusion injury by regulating
      myocardial apoptosis and angiogenesis.
AB  - Angiogenic factor with G patch and FHA domains 1 (AGGF1) is a newly identified
      proangiogenic protein, which plays an important role in vascular disease and
      angiogenesis. However, its role in myocardial ischemia/reperfusion (I/R) injury
      remains unknown. This study investigated whether AGGF1 is involved in the
      pathogenesis of mouse myocardial I/R injury and the underlying mechanisms. Wild
      type (WT) C57BL/6 J mice were treated at 30 min prior to I/R injury with anti
      AGGF1 neutralizing antibody (3 mg/kg) or recombinant human AGGF1 (rhAGGF1, 0.25
      mg/kg). After I/R injury, the infarct size, the number of TUNEL-positive
      cardiomyocytes, Bax/Bcl2 ratio, inflammatory cytokine expression and angiogenesis
      were markedly increased as compared with sham control. Treatment of WT mice with
      anti-AGGF1 neutralizing antibody resulted in exaggeration of myocardial I/R
      injury but reducing angiogenesis. In contrast, administration of rhAGGF1 markedly
      reversed these effects. Furthermore, anti-AGGF1- or rhAGGF1-mediated effects on
      I/R-induced cardiac apoptosis, inflammation and angiogenesis were dose dependent.
      In addition, the protective effects of AGGF1 on cardiomyocyte apoptosis and
      inflammation were confirmed in cultured cardiomyocytes after I/R. Finally, these
      effects were associated with activation of ERK1/2, Stat3 and HIF-1alpha/VEGF
      pathways and inhibition of activation of NF-kappaB, p53 and JNK1/2 pathways. In
      conclusion, we report the first in vivo and in vitro evidence that AGGF1 reduces
      myocardial apoptosis and inflammation and enhances angiogenesis, leading to
      decreased infarct size after I/R injury. These results may provide a novel
      therapeutic approach for ischemic heart diseases.

PMID- 24893994
TI  - Candesartan cilexetil microemulsions for transdermal delivery: formulation, in
      vitro skin permeation and stability assessment.
AB  - The work investigates the formulation and evaluation of microemulsions containing
      olive oil, Tween 80 and isopropyl alcohol for transdermal candesartan cilexetil
      delivery. The pseudoternary phase diagram was constructed to determine
      composition of microemulsions. These formulated microemulsions were evaluated for
      in vitro skin permeation and stability. The microemulsion containing 72 % olive
      oil, 8 % water, 15 % Tween 80, and 5 % isopropylalcohol showed maximum viscosity
      of 29.54+/-0.32 mPas, average small droplet size of 180.90 nm, smaller
      polydispersity index of 0.37, zeta potential of -12.20 and maximum candesartan
      cilexetil permeation flux of 0.49+/-0.05 MUg/cm2/h through excised porcine skin.
      The degradation of candesartan cilexetil microemulsions after 3 months storage
      was found low and its shelf-life was calculated as 3.92 years at room
      temperature. 

PMID- 24893992
TI  - Homeostatic control of polo-like kinase-1 engenders non-genetic heterogeneity in
      G2 checkpoint fidelity and timing.
AB  - The G2 checkpoint monitors DNA damage, preventing mitotic entry until the damage
      can be resolved. The mechanisms controlling checkpoint recovery are unclear.
      Here, we identify non-genetic heterogeneity in the fidelity and timing of damage
      induced G2 checkpoint enforcement in individual cells from the same population.
      Single-cell fluorescence imaging reveals that individual damaged cells experience
      varying durations of G2 arrest, and recover with varying levels of remaining
      checkpoint signal or DNA damage. A gating mechanism dependent on polo-like kinase
      1 (PLK1) activity underlies this heterogeneity. PLK1 activity continually
      accumulates from initial levels in G2-arrested cells, at a rate inversely
      correlated to checkpoint activation, until it reaches a threshold allowing
      mitotic entry regardless of remaining checkpoint signal or DNA damage. Thus,
      homeostatic control of PLK1 by the dynamic opposition between checkpoint
      signalling and pro-mitotic activities heterogeneously enforces the G2 checkpoint
      in each individual cell, with implications for cancer pathogenesis and therapy. 

PMID- 24893995
TI  - Preparation and characterization of rivastigmine loaded human serum albumin (HSA)
      nanoparticles.
AB  - The aim of the present study was to develop and characterize rivastigmine loaded
      Human Serum Albumin (HSA) nanoparticles (NPs) for sustained release. Rivastigmine
      tartrate (RT) is a short acting cholinesterase inhibitor (ChEI) used for
      Alzheimer's disease (AD). In the present study sustained release nanoparticulate
      formulation of RT was prepared, optimized (using 32 factorial design) and
      characterized (using biodegradable polymer HSA as a carrier). HSA NPs were
      prepared by desolvation-crosslinking technique using ethanol with variable
      drug/polymer ratios (1:1, 1:2, 1:3, and 1:5) and using glutaraldehyde as a
      crosslinking agent. All prepared nanoparticles were coated with polysorbate-80 to
      facilitate brain targeting via endocytosis. Effect of key formulation variables
      on particle size (PS) and percentage drug entrapment (PDE) of NPs was studied by
      using 32 factorial design. Among different ratios studied, 1:2 showed minimum PS
      of 83.71 +/- 4.2 nm with highest PDE of 81.46 +/- 0.76 %. FTIR interpretation
      showed that there is no interaction between the drug and excipients used, DSC
      thermograms indicated that RT was dispersed as an amorphous state in HSA NPs. SEM
      studies indicated that the drug was completely entrapped in HSA NPs. In vitro
      studies showed 55.59 +/- 3.80% release of drug from HSA NPs in 12 h. The
      experimental results showed the suitability of HSA nanoparticles as a potential
      carrier for providing sustained delivery of RT. 

PMID- 24893996
TI  - Development and optimization of press coated floating pulsatile drug delivery of
      sumatriptan succinate.
AB  - Floating pulsatile is combined approach designed according to circadian rhythm to
      deliver the drug at right time, in right quantity and at right site as per
      pathophysiological need of disease with prolong gastric residence and lag phase
      followed by burst release. As the migraine follows circadian rhythm in which
      headache is more painful at the awakening time, the dosage form should be given
      during night time to release drug when pain get worsen. Present work deals with
      formulation and optimization of floating pulsatile tablet of sumatriptan
      succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed
      burst release. Lag time was maintained using swellable polymer as polyoxN12K and
      xanthum gum. 3(2) experimental design was carried out. Developed formulations
      were evaluated for physical characteristics, in vitro and in vivo study.
      Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum
      (26.56%) of total polymer weight showed floating lag time 15+/-2 sec, drug
      content 99.58+/-0.2 %, hardness 6+/-0.2 Kg/cm(2) and drug release 99.54+/-2% with
      pulsatile manner followed lag period of 7+/-0.1h. In vivo x-ray study confirms
      prolong gastric residence of system. Programmable pulsatile release has been
      achieved by formulation F2 which meet demand of chronotherapeutic objective of
      migraine. 

PMID- 24893998
TI  - Forages and Pastures Symposium: assessing drought vulnerability of agricultural
      production systems in context of the 2012 drought.
AB  - Weather and climate events and agronomic enterprise are coupled via crop
      phenology and yield, which is temperature and precipitation dependent. Additional
      coupling between weather and climate and agronomic enterprise occurs through
      agricultural practices such as tillage, irrigation, erosion, livestock
      management, and forage. Thus, the relationship between precipitation,
      temperature, and yield is coupled to the relationship between temperature,
      precipitation, and drought. Unraveling the different meteorological and
      climatological patterns by comparing different growing seasons provides insight
      into how drought conditions develop and what agricultural producers can do to
      mitigate and adapt to drought conditions. The 2012 drought in the United States
      greatly impacted the agricultural sector of the economy. With comparable severity
      and spatial extent of the droughts of the 1930s, 1950s, and 1980s, the 2012
      drought impacted much of the U.S. crop and livestock producers via decreased
      forage and feed. This brief summary of drought impacts to agricultural production
      systems includes 1) the basics of drought; 2) the meteorology and climatology
      involved in forecasting, predicting, and monitoring drought with attribution of
      the 2012 drought explored in detail; and 3) comparative analysis completed
      between the 2011 and 2012 growing season. This synthesis highlights the complex
      nature of drought in agriculture production systems as producers prepare for
      future climate variability. 

PMID- 24893997
TI  - Effect of diet on microRNA expression in ovine subcutaneous and visceral adipose
      tissues.
AB  - Knowledge of the molecular mechanisms that regulate ovine adipogenesis is very
      limited. MicroRNAs (miRNA) have been reported as one of the regulatory mechanisms
      of adipogenesis. This study aimed to compare the expression of miRNA related to
      ovine adipogenesis in different adipose depots and to investigate whether their
      expression is affected by dietary fatty acid composition. We also investigated
      the role of miRNA in adipogenic gene regulation. Subcutaneous and visceral
      adipose tissue samples were collected at slaughter from 12 Canadian Arcott lambs
      fed a barley-based finishing diet where an algae meal (DHA-Gold; Schizochytrium
      spp.) replaced flax oil and barley grain at 0 or 3% DM (n = 6). Total RNA from
      each tissue was subjected to quantitative real time (qRT-) PCR analysis to
      determine the expression of 15 selected miRNA including 11 identified from bovine
      adipose tissues and 4 conserved between bovine and ovine species. MicroRNAs were
      differentially expressed according to diet in each tissue depot (miR-142-5p and
      miR-376d) in visceral and miR-142-5p, miR-92a, and miR-378 in subcutaneous
      adipose tissue; P <= 0.05) and in each tissue depot depending on diet (miR-101,
      miR-106, miR-136, miR-16b, miR-196a-1, miR-2368*, miR-2454, miR-296, miR-376d,
      miR-378, and miR-92a in both control and DHA-G diets and miR-478 in control; P <=
      0.05). Six miRNA were subjected to functional analysis and 3 genes of interest
      (ACSL1, PPARalpha, and C/EBPalpha) were validated by qRT-PCR. Both diet and
      tissue depot affected expression levels of all 3 genes (P < 0.05). miR-101, miR
      106, and miR-136 were negatively correlated with their respective predicted gene
      targets C/EBPalpha, PPARalpha, and ACSL1 in subcutaneous adipose tissue of lambs
      fed DHA-G. Yet miR-142-5p and miR-101 showed no correlation with ACSL1 or
      C/EBPalpha. The variability in expression patterns of miRNA across adipose depots
      reflects the tissue specific nature of adipogenic regulation. Although the
      examined miRNA appear to be conserved across ruminant species, our results
      indicate the presence of ovine specific regulatory mechanisms that can be
      influenced by diet. 

PMID- 24893999
TI  - Litter size components in a full diallel cross of four maternal lines of rabbits.
AB  - A crossbreeding experiment between 4 Spanish maternal lines of rabbits was
      performed to estimate crossbreeding effects on litter size components. The
      experiment was designed as a complete diallel cross involving 4 lines selected
      for litter size at weaning (A, V, H, and LP [L]) and their 12 simple crosses.
      Does from these 16 genetic groups were distributed among 4 Spanish farms, but
      only V line was present in all farms, allowing connectivity of the data. A total
      of 2,015 does in the third, fourth, or fifth gestations were subjected to
      laparoscopy. The recorded traits were ovulation rate (OR), number of implanted
      embryos (IE), total born (TB), embryo survival (ES), foetal survival (FS), and
      prenatal survival (PS). The differences in direct genetic effects, maternal
      genetic effects, and individual heterosis between the lines were estimated
      according to Dickerson's model. Line A was significantly inferior to lines V and
      H, whereas line LP was similar to A line, but for FS and PS, line A showed the
      best values, followed by line LP. Comparing crossbred groups to line V,
      significant differences were shown favoring crossbred groups for OR and IE. The
      crossbred groups presented high implantation rate, but the foetal survival was
      lower than in V line. Important values for commercial production were presented
      by some crosses for OR (HV, 1.26 ova), IE (AH, 1.50 embryos; HV, 1.41 embryos),
      and TB (AH, 0.82 rabbits; HV, 0.78 rabbits). Relevant and significant reciprocal
      effects were found, especially for OR in all cases except the LV and VL crosses.
      These differences become nonsignificant in most of the other traits. Regarding
      direct genetic effects, line A presented lower estimates than the other lines
      with important values for OR, but the opposite was observed for FS. The maternal
      effects were significant only for some contrasts in OR and revealed that the LP
      line was inferior to the others (1.08 ova compared to the A line, 1.23 compared
      to the H line, and 0.38 compared to the V line). In general, high positive values
      for heterosis were found in crossbred does for OR and IE. The crosses, where
      lines A and H were involved, showed significant heterosis. The highest values
      were obtained by crossing lines A and H (1.18 ova for OR, 1.87 embryos for IE)
      followed by the cross between lines H and V. Crosses between line LP and the
      other lines had a negative heterosis for FS and PS. 

PMID- 24894000
TI  - Effect of vitamin D status improvement with 25-hydroxycholecalciferol on skeletal
      muscle growth characteristics and satellite cell activity in broiler chickens.
AB  - Skeletal muscle satellite cells (SC) play a critical role in the hypertrophic
      growth of postnatal muscle. Increases in breast meat yield have been consistently
      observed in broiler chickens fed 25-hydroxycholecalciferol (25OHD3), but it is
      unclear whether this effect is mediated by SC. Thus, our objective was to
      determine the effect of vitamin D status improvement by replacing the majority of
      dietary vitamin D3 (D3) with 25OHD3 on SC activity and muscle growth
      characteristics in the pectoralis major (PM) and the biceps femoris (BF) muscles.
      Day-old, male Ross 708 broiler chickens (n = 150) were fed 1 of 2 corn and
      soybean meal-based diets for 49 d. The control diet (CTL) contained 5,000 IU D3
      per kg of diet and the experimental diet (25OHD3) contained 2,240 IU D3 per kg of
      diet + 2,760 IU 25OHD3 per kg of diet. Ten birds per treatment were harvested
      every 7 d. Two hours before harvest, birds were injected intraperitoneally with
      5'-bromo-2'deoxyuridine (BrdU) to label mitotically active cells. Blood was
      collected from each bird at harvest to measure circulating concentrations of
      25OHD3, a marker of vitamin D status. The PM and BF muscles were weighed and
      processed for cryohistological determination of skeletal muscle fiber cross
      sectional area, enumeration of Myf-5+ and Pax7+ SC, and mitotically active
      (BrdU+) SC using immunofluorescence microscopy. Circulating 25OHD3 concentrations
      were greater in 25OHD3-fed birds on d 7, 14, 21, 28, 35, 42, and 49 when compared
      with CTL (P < 0.001). Growth performance and feed efficiency did not differ among
      dietary treatments (P > 0.10). Improved vitamin D status as a result of feeding
      25OHD3 increased the number of mitotically active (Pax7+;BrdU+) SC (P = 0.01) and
      tended to increase the density of Pax7+ SC (P = 0.07) in the PM muscles of
      broilers on d 21 and 35, respectively. Broiler chickens fed 25OHD3 also tended to
      have greater Myf-5+ SC density (P = 0.09) on d 14, greater total nuclear density
      (P = 0.05) on d 28, and a greater muscle fiber cross-sectional area (P = 0.09) on
      d 49 in their PM muscles compared with CTL birds. Collectively, these results
      suggest that improvement of vitamin D status by replacing the majority of D3 in
      the diet with 25OHD3 can stimulate SC activity in the predominantly fast-twitch
      PM muscle and provide evidence toward understanding the mechanism behind
      previously observed increases in breast meat yield in 25OHD3-fed commercial
      broiler chickens. 

PMID- 24894001
TI  - Beef Species Symposium: nutrient requirements of the beef female in extensive
      grazing systems--considerations for revising the Beef NRC.

PMID- 24894002
TI  - Dietary antioxidants at supranutritional doses improve oxidative status and
      reduce the negative effects of heat stress in sheep.
AB  - The present study was undertaken to investigate the impact of heat (thermal)
      stress and dietary antioxidant supplementation on the oxidative and physiological
      status of sheep. Twenty-four Merino * Poll Dorset crossbred ewes were housed in 1
      of 2 climatic chambers (thermoneutral or heat stress) and offered either a
      control (10 IU vitamin E/kg DM and 0.24 mg Se/kg DM) or high antioxidant (100 IU
      vitamin E/kg DM and 1.20 mg Se/kg DM) diet. The sheep were exposed to 2 thermal
      (temperature) treatments (thermoneutral [TN]: 18-21 degrees C and 26-30% relative
      humidity; and heat stress [HS]: 28-40 degrees C and 40-50% relative humidity) for
      2 wk in a single reversal design. After 1 wk of dietary treatment, animals in 1
      chamber were subjected to HS for 1 wk, with the temperature being increased to 40
      degrees C between 0900 and 1700 h and then maintained at 28 degrees C overnight.
      Those sheep in the TN group were maintained at 18 to 21 degrees C. Physiological
      parameters were recorded 4 times a day (0900, 1300, 1700, and 2100 h) and blood
      samples were collected on d 1 and 7 of heat treatment. Plasma samples and red
      blood cell lysates were assayed for oxidative stress biomarkers. The thermal
      treatments were then reversed and the above measures repeated. All measured
      physiological parameters were elevated (P < 0.001) by thermal treatment.
      Respiration rate was lower during HS in sheep supplemented with antioxidants as
      indicated by a diet * temperature * time interaction (P = 0.010). There was 13%
      decline (P = 0.014) in feed intake of the unsupplemented animals during HS
      whereas the same was maintained in sheep supplemented with high doses of
      antioxidants. Plasma reactive oxygen metabolites concentrations were reduced (114
      vs. 85 units/dL; P < 0.005) while biological antioxidant potential tended to be
      increased (3,688 vs. 3,985 MUmol/L; P = 0.070) in heat stressed sheep
      supplemented with antioxidants. The oxidative stress index was 30% lower (P <
      0.001) in supplemented sheep (2.16 +/- 0.06 arbitrary units) during HS than in
      unsupplemented sheep (3.12 +/- 0.08 arbitrary units). Plasma advanced oxidation
      protein products tended (P = 0.070) to decrease in antioxidant supplemented heat
      stressed sheep as compared to their unsupplemented counterparts. It was concluded
      that heat stress negatively affects the oxidative status of sheep along with the
      physiological responses and some of these affects can be ameliorated through
      dietary antioxidants supplementation at supranutritional concentrations. 

PMID- 24894005
TI  - Effect of age on bovine subcutaneous fat proteome: molecular mechanisms of
      physiological variations during beef cattle growth.
AB  - Fat deposition influences both meat quality and animal productivity. However, it
      is not clear how fat development is regulated in growing and fattening beef
      cattle. This study characterized proteomic changes in subcutaneous adipose tissue
      from steers fed a high-grain diet in an effort to understand the molecular
      mechanisms of fat development during feedlot production. Eight British
      Continental crossbred steers had two subcutaneous adipose tissue biopsies at 12
      and 15 mo of age. Protein expression in fat samples was profiled using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). During the finishing period,
      steers increased subcutaneous adipose tissue mass with concomitant changes in the
      proteome profile, but the nature of these changes varied among steers. The
      expression of 123 out of 627 identified proteins differed (P <: 0.05) between 2
      ages. Functional analyses on differentially expressed proteins revealed that
      20.2% of them were associated with cellular growth and proliferation of adipose
      tissue. There were 17 out of 108 differentially expressed proteins associated
      with lipid metabolism, which were acyl-CoA synthetase medium-chain family member
      1 (ACSM1), annexin A1 (ANXA1), apolipoprotein C-III (APOC3), apolipoprotein H
      (beta-2-glycoprotein I; APOH), EH-domain containing 1 (EHD1), coagulation factor
      II (thrombin; F2), gelsolin (GSN), lamin A/C (LMNA), mitogen-activated protein
      kinase kinase 1 (MAP2K1), myosin, heavy chain 9, non-muscle (MYH9), orosomucoid 1
      (ORM1), protein disulfide isomerase family A, member 3 (PDIA3), retinol binding
      protein 4, plasma (RBP4), renin binding protein (RENBP), succinate dehydrogenase
      complex, subunit A, flavoprotein (Fp; SDHA), serpin peptidase inhibitor, clade C
      (antithrombin), member 1 (SERPINC1), and serpin peptidase inhibitor, clade G (C1
      inhibitor), member 1 (SERPING1). Further analysis of the expression levels of
      proteins associated with lipid metabolism indicated a downregulation in the
      synthesis of fatty acids at the cellular level at 15 compared to 12 mo of age.
      These results suggest that even though adipose tissue expanded, fat anabolism was
      reduced in adipocytes during growth, revealing a coordinated balance between
      subcutaneous fat mass and the cellular abundance of lipogenic proteins to control
      the rate of fat deposition in growing beef cattle. The findings observed in this
      study expand our understanding on how proteome of bovine adipose tissue is
      regulated during growth, which might help the development in the future of new
      strategies to manipulate adiposity in beef cattle in a manner that improves meat
      quality and animal productivity. 

PMID- 24894003
TI  - Reproduction Symposium: hypothalamic neuropeptides and the nutritional
      programming of puberty in heifers.
AB  - Nutrition during the juvenile period has a major impact on timing reproductive
      maturity in heifers. Restricted growth delays puberty, whereas elevated BW gain
      advances the onset of puberty. The initiation of high-frequency episodic release
      of GnRH and, consequently, LH during the peripubertal period is crucial for
      maturation of the reproductive axis and establishment of normal estrous cycles.
      Nutritional signals are perceived by metabolic-sensing cells in the hypothalamus,
      which interact with estradiol-receptive neurons to regulate the secretory
      activity of GnRH neurons. The orexigenic peptide, neuropeptide Y (NPY), and the
      anorexigenic peptide derived from the proopiomelanocortin (POMC) gene, melanocyte
      stimulating hormone alpha (alphaMSH), are believed to be major afferent pathways
      that transmit inhibitory (NPY) and excitatory (alphaMSH) inputs to GnRH neurons.
      The neuropeptide kisspeptin is considered a major stimulator of GnRH secretion
      and has been shown to mediate estradiol's effect on GnRH neuronal activity.
      Kisspeptin may also integrate the neuronal pathways mediating the metabolic and
      gonadal steroid hormone control of gonadotropin secretion. Recent studies in our
      laboratories indicate that functional and structural changes in the pathways
      involving NPY, POMC, and kisspeptin neurons occur in response to high rates of BW
      gain during the juvenile period in heifers. Changes include regulation of
      expression in NPY, POMC, and KISS1 and plasticity in the neuronal projections to
      GnRH neurons and within the neuronal network comprising these cells. Moreover, an
      intricate pattern of differential gene expression in the arcuate nucleus of the
      hypothalamus occurs in response to feeding high concentrate diets that promote
      elevated BW gain. Genes involved include those controlling feeding intake and
      cell metabolism, neuronal growth and remodeling, and synaptic transmission.
      Characterizing the cellular pathways and molecular networks involved in the
      mechanisms that control the timing of pubertal onset will assist in improving
      existing strategies and facilitate the development of novel approaches to program
      puberty in heifers. These include the use of diets that elevate BW gain during
      strategic periods of prepubertal development. 

PMID- 24894006
TI  - Relationships between residual feed intake and hepatic mitochondrial function in
      growing beef cattle.
AB  - The objective of this study was to evaluate the relationship between hepatic
      mitochondrial function and residual feed intake (RFI) in growing beef cattle. In
      Trial 1, RFI was measured in 29 Angus heifers (initial BW = 258.0 +/- 24.9 kg)
      from divergent IGF-I selection lines created at the Eastern Agricultural Research
      Station (The Ohio State University) fed a grain-based diet (calculated ME = 2.85
      Mcal/kg DM). In Trial 2, RFI was measured in 119 Santa Gertrudis steers (initial
      BW = 308.4 +/- 28.1 kg) fed a roughage-based diet (calculated ME = 2.21 Mcal/kg
      DM). At the end of the RFI measurement period, cattle in Trial 1 (n = 7 low RFI
      and n = 7 high RFI) and in Trial 2 (n = 6 low RFI and n = 8 high RFI) with
      measures of RFI exceeding 0.5 (Trial 1) or 1.0 (Trial 2) SD from the mean RFI
      were selected to measure mitochondrial function. Overall ADG, DMI, and RFI were
      1.19 +/- 0.15, 9.31 +/- 1.12, and 0.00 +/- 0.63 kg/d and 0.83 +/- 0.16, 9.48 +/-
      1.00, and 0.00 +/- 0.86 kg/d in Trial 1 and 2, respectively. Cattle with low RFI
      consumed 13 and 24% less (P < 0.05) DM and had 14 and 56% greater (P < 0.05) G:F
      than cattle with high RFI in Trial 1 and 2, respectively, even though ADG and BW
      were similar (P > 0.10). In Trial 1, cattle with low RFI tended (P = 0.06) to
      have greater state 3 respiration rates than cattle with high RFI, but state 3
      respiration rates were similar (P > 0.10) between cattle with low and high RFI in
      Trial 2. In both trials, cattle with low RFI had greater (P < 0.05) acceptor
      control ratios than their high RFI counterparts. The respiratory control ratio
      tended (P = 0.09) to be greater for cattle with low RFI compared with high RFI
      cattle in Trial 1, but no difference (P > 0.10) was observed in Trial 2. Proton
      leak kinetics were similar (P > 0.05) between cattle with low and high RFI in
      both trials. These data suggest that ADP has greater control of oxidative
      phosphorylation in liver mitochondrial of cattle with low RFI compared to their
      high RFI counterparts. 

PMID- 24894007
TI  - High-biomass forests of the Pacific Northwest: who manages them and how much is
      protected?
AB  - To examine ownership and protection status of forests with high-biomass stores
      (>200 Mg/ha) in the Pacific Northwest (PNW) region of the United States, we used
      the latest versions of publicly available datasets. Overlay, aggregation, and GIS
      based computation of forest area in broad biomass classes in the PNW showed that
      the National Forests contained the largest area of high-biomass forests (48.4 %
      of regional total), but the area of high-biomass forest on private lands was
      important as well (22.8 %). Between 2000 and 2008, the loss of high-biomass
      forests to fire on the National Forests was 7.6 % (236,000 ha), while the loss of
      high-biomass forest to logging on private lands (364,000 ha) exceeded the losses
      to fire across all ownerships. Many remaining high-biomass forest stands are
      vulnerable to future harvest as only 20 % are strictly protected from logging,
      while 26 % are not protected at all. The level of protection for high-biomass
      forests varies by state, for example, 31 % of all high-biomass federal forests in
      Washington are in high-protection status compared to only 9 % in Oregon. Across
      the conterminous US, high-biomass forest covers <3 % of all forest land and the
      PNW region holds 56.8 % of this area or 5.87 million ha. Forests with high
      biomass stores are important to document and monitor as they are scarce, often
      threatened by harvest and development, and their disturbance including timber
      harvest results in net C losses to the atmosphere that can take a new generation
      of trees many decades or centuries to offset. 

PMID- 24894008
TI  - Farmers' perceived risks of climate change and influencing factors: a study in
      the Mekong Delta, Vietnam.
AB  - Many countries are confronting climate change that threatens agricultural
      production and farmers' lives. Farmers' perceived risks of climate change and
      factors influencing those perceived risks are critical to their adaptive behavior
      and well-planned adaptation strategies. However, there is limited understanding
      of these issues. In this paper, we attempt to quantitatively measure farmers'
      perceived risks of climate change and explore the influences of risk experience,
      information, belief in climate change, and trust in public adaptation to those
      perceived risks. Data are from structured interviews with 598 farmers in the
      Mekong Delta. The study shows that perceived risks to production, physical
      health, and income dimensions receive greater priority while farmers pay less
      attention to risks to happiness and social relationships. Experiences of the
      events that can be attributed to climate change increase farmers' perceived
      risks. Information variables can increase or decrease perceived risks, depending
      on the sources of information. Farmers who believe that climate change is
      actually happening and influencing their family's lives, perceive higher risks in
      most dimensions. Farmers who think that climate change is not their concern but
      the government's, perceive lower risks to physical health, finance, and
      production. As to trust in public adaptation, farmers who believe that public
      adaptive measures are well co-ordinated, perceive lower risks to production and
      psychology. Interestingly, those who believe that the disaster warning system is
      working well, perceive higher risks to finance, production, and social
      relationships. Further attention is suggested for the quality, timing, and
      channels of information about climate change and adaptation. 

PMID- 24894010
TI  - Sharing information on cardiovascular disease prevention across Europe.

PMID- 24894009
TI  - Enhancement of Rituximab-induced cell death by the physical association of CD20
      with CD40 molecules on the cell surface.
AB  - CD20 is an attractive therapeutic target given the success of its monoclonal
      antibody, Rituximab, in the treatment of B-cell malignancies and B-cell-mediated
      autoimmune diseases. Treatment with Rituximab causes a rapid depletion of B cells
      and a decrease in disease symptoms. Despite the clinical efficiency of Rituximab,
      its mechanism of action is not completely understood. In this study, we aimed at
      further investigating the Rituximab-induced cell death and the factors affecting
      such responses. Our results indicate that Rituximab-induced cell death depends on
      the nature of the cells and levels of CD20 expression on the cell surface.
      Coexpression of CD20 with CD40, a member of the TNF receptor family that is known
      to be physically associated with CD20 on the cell surface, enhances the apoptotic
      response induced by Rituximab. Inhibiting the formation of CD40 disulfide-bound
      homodimers, a process required for some CD40 signaling, further enhances
      Rituximab-induced cell death. Cell death induced by anti-CD40 mAb is also
      upregulated by the presence of CD20, suggesting a bidirectional influence of the
      CD20/CD40 association. Moreover, treating cells with both anti-CD20 and anti-CD40
      antibodies improves the cell death response induced by a single-agent treatment.
      These results highlight the role of the CD20/CD40 association in triggering B
      cell depletion and may pave the way for an alternative more efficient therapeutic
      strategy in treating B-cell-mediated disorders. 

PMID- 24894012
TI  - A case of post-haemodialysis, massive haematoma in an SLE patient.

PMID- 24894011
TI  - Clinicopathologic features and prognostic implications of NOK/STYK1 protein
      expression in non-small cell lung cancer.
AB  - BACKGROUND: The expression of novel oncogenic kinase (NOK), a member of the
      protein tyrosine kinase (PTK) family, has been observed in several human
      malignancies including non-small cell lung cancer (NSCLC). However, the clinic
      relevance of NOK expression in NSCLC remains unclear. METHODS: In this study, NOK
      expression in tumor cells was assessed using immunohistochemical methods in 191
      patients with resected NSCLC. The association of NOK expression with
      clinicopathological parameters, including the Ki-67 labeling index (LI), was also
      evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models
      were used to estimate the effect of NOK expression on survival. RESULTS: Data
      showed that NOK was expressed in 75.4% and 14.1% of cancer lesions and
      corresponding adjacent non-cancerous tissue, respectively. Out of all the
      clinicopathological factors analyzed, NOK expression was significantly correlated
      with the grade of tumor differentiation (P=0.035), pTNM stage (P=0.020),
      lymphatic metastasis (P=0.005) and high Ki-67 LI (P<0.001). NOK positive NSCLC
      patients had a significantly shorter survival time (P=0.004, Log-rank test) and
      the prognostic significance of NOK expression was apparent in squamous cell
      carcinoma patients (P=0.022). Multivariate analysis indicated that NOK expression
      may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.731;
      P=0.043). CONCLUSIONS: Our results indicate that NOK expression is of clinical
      significance and can serve as a prognostic biomarker in NSCLC.

PMID- 24894015
TI  - The use of antipsychotic medication by community-dwelling people with dementia:
      an exploratory statistical analysis.

PMID- 24894013
TI  - The actual scenario of neoadjuvant chemotherapy of breast cancer in developing
      country: a report of 80 cases of breast cancer from a tertiary cancer center in
      India.
AB  - BACKGROUND: Preoperative or neoadjuvant chemotherapy is an option in patients
      with large operable breast cancer to facilitate the breast conservation and to
      downstage the disease to make inoperable breast cancer to operable one. It is
      also called the window of opportunity; it provides a unique opportunity to derive
      biological information related to tumor response. Neoadjuvant chemotherapy has
      been compared with standard, postoperative adjuvant chemotherapy with goals of
      improving survival and facilitating local therapies. Unfortunately, neoadjuvant
      chemotherapy does not seem to improve overall survival. There is a lack of data
      from India regarding the neoadjuvant chemotherapy. The present study was carried
      out to assess the response to neoadjuvant chemotherapy in breast cancer.
      MATERIALS AND METHODS: We retrospectively analyzed the records of patients who
      were started on neoadjuvant chemotherapy (NACT) at our center for 1 year (August
      2012 to July 2013). Case files were thoroughly reviewed, and patient's
      characteristics (age, pre-/postmenopausal status, family history of
      breast/ovarian/other cancer), mode of detection, treatment, and histological
      features were analyzed. RESULTS: Out of 322 patients with breast cancer
      registered in our institute, 80 patients received neoadjuvant chemotherapy.
      Median age was 45 years. The most common presentation was left-sided breast lump
      (Lt > Rt) with a median duration of symptoms was 4 months. Postmenopausal
      patients (53.75 %) were more than premenopausal (46.25 %). Seventy-two patients
      were stage III and 8 were stage II disease. Bilateral breast cancer was seen in 8
      patients. Most common histological type was invasive ductal carcinoma (95 %).
      Estrogen receptor (ER) and/or progesterone (PR) positive were seen in 47 (58.75
      %) patients. Ten patients were HER2 positive and ER/PR negative, and 5 patients
      were triple positive. Triple-negative patients were 22 (27.5 %). The most common
      neoadjuvant chemotherapy protocol used was FEC. Clinical response before surgery
      was CR 13 %, PR 68.68 %, stable disease 11.62 %, and progressive disease 4.65 %.
      Pathological CR was seen in 6.9 % of tumors. Nodal status at surgery was ypN0-40
      %, ypN1-28. 5 %. ypN2-27 %, and ypN3-4.28 %. CONCLUSION: In a population of
      predominantly locally advanced patients, NACT with anthracyclines yielded pCR
      rates comparable to published studies. There were a high proportion of HER2
      positive patients, most of whom could not receive anti-HER2 therapy due to
      financial reasons.

PMID- 24894016
TI  - The RHD(1227G>A) DEL-associated allele is the most prevalent DEL allele in
      Australian D- blood donors with C+ and/or E+ phenotypes.
AB  - BACKGROUND: Red blood cells (RBCs) with D antigen levels only detected by anti-D
      adsorption-elution and an antiglobulin test express a DEL phenotype. For two DEL
      types, including RHD(1227G>A), immunization of D- recipients has been reported.
      This study's aim was to measure the prevalence of DEL-associated RHD alleles in a
      cohort of Australian D- donors to develop a model to estimate alloimmunization
      risk. STUDY DESIGN AND METHODS: D-, C+ and/or E+ blood donors were screened for
      RHD exons using quantitative polymerase chain reaction. Donors with RHD signals
      were DEL phenotyped with MCAD6 anti-D. RHD alleles were characterized via single
      nucleotide polymorphism array or sequencing. Extended DEL phenotyping was
      performed with an anti-D panel. RESULTS: Among 2027 donors, 39 carried RHD
      alleles that have been previously reported to associate with either the DEL or
      the weak D phenotype. An additional five donors carried previously unreported RHD
      alleles and exhibited the DEL phenotype: RHD(IVS2-2delA), RHD(IVS1+5G>C),
      RHD(ex9:del/CE), and RHD(ex8:del/CE) represented twice. In total, DEL/weak D
      associated RHD alleles were detected in 44 of 2027 donors or 2.17% (95%
      confidence interval, 1.54%-2.81%). The RHD(1227G>A) DEL allele was the most
      frequent (n = 16). The risk of transfusing D- females not more than 40 years of
      age with an RHD(1227G>A) DEL RBC unit (when managed as D-) is estimated to be one
      in 149,109 transfusions (range, 100,680-294,490). CONCLUSION: DEL/weak D
      associated RHD alleles were found in 2.17% of Australian D-, C+ and/or E+ blood
      donors. This differs from previous European reports in that the clinically
      significant RHD(1227G>A) DEL allele is the most prevalent.

PMID- 24894018
TI  - Epithelioid glioblastoma arising from pleomorphic xanthoastrocytoma with the BRAF
      V600E mutation.
AB  - Pleomorphic xanthoastrocytoma (PXA) is classified by the World Health
      Organization as a grade II astrocytic tumor with relatively favorable prognosis
      among gliomas. A valine-to-glutamic acid substitution at position 600 of the
      serine/threonine-protein kinase BRAF (BRAF V600E) mutation, which is commonly
      found in PXA, has recently been detected in approximately 50% of all epithelioid
      glioblastoma (GBM) cases. We herein report a case of epithelioid GBM developing
      at the site of a left temporal PXA 13 years after the treatment of the primary
      tumor. The BRAF V600E mutation was detected in both tumors. These findings
      suggest that epithelioid GBM may arise from a PXA with a BRAF V600E mutation.

PMID- 24894017
TI  - The predictors of glucose screening: the contribution of risk perception.
AB  - BACKGROUND: The prevention of type 2 diabetes is a challenge for health
      institutions. Periodic blood glucose screening in subjects at risk for developing
      diabetes may be necessary to implement preventive measures in patients prior to
      the manifestation of the disease and to efficiently diagnose diabetes. Not only
      medical aspects, but also psychological and social factors, such as the
      perception of risk (the individuals' judgment of the likelihood of experiencing
      an adverse event) influence healthy or preventive behaviors. It is still unknown
      if risk perception can have an effect on health behaviors aimed at reducing the
      risk of diabetes (glucose screening). The objective of study was to identify
      factors that influence glucose screening frequency. METHODS: Eight hundred
      randomized interviews, which were stratified by socioeconomic level, were
      performed in Mexico City. We evaluated the perception of risk of developing
      diabetes, family history, health status and socioeconomic variables and their
      association with glucose screening frequency. RESULTS: Of the study participants,
      55.6% had not had their glucose levels measured in the last year, whereas 32.8%
      of the subjects reported having monitored their glucose levels one to three times
      per year and 11.5% had their levels monitored four or more times per year. Risk
      perception was significantly associated with the frequency of blood glucose
      screening. Having a first-degree relative with diabetes, being older than 45
      years and belonging to a middle socioeconomic level increased the probability of
      subjects seeing a doctor for glucose screening. CONCLUSIONS: Glucose screening is
      a complex behavior that involves the subjects' perception of threat, defined as
      feeling vulnerable to the development of diabetes, which is determined by the
      subject's environment and his previous experience with diabetes.

PMID- 24894019
TI  - Analysis of the chemotactic behaviour of Leptospira using microscopic agar-drop
      assay.
AB  - Chemotaxis allows bacterial cells to migrate towards or away from chemical
      compounds. In the present study, we developed a microscopic agar-drop assay (MAA)
      to investigate the chemotactic behaviour of a coiled spirochete, Leptospira
      biflexa. An agar drop containing a putative attractant or repellent was placed
      around the centre of a flow chamber and the behaviour of free-swimming cells was
      analysed under a microscope. MAA showed that L. biflexa cells gradually
      accumulated around an agar drop that contained an attractant such as glucose.
      Leptospira cells often spin without migration by transformation of their cell
      body. The frequency at which cells showed no net displacement decreased with a
      higher glucose concentration, suggesting that sensing an attractive chemical
      allows these cells to swim more smoothly. Investigation of the chemotactic
      behaviour of these cells in response to different types of sugars showed that
      fructose and mannitol induced negative chemotactic responses, whereas xylose and
      lactose were non-chemotactic for L. biflexa. The MAA developed in this study can
      be used to investigate other chemoattractants and repellents.

PMID- 24894020
TI  - A murine model of cervical spinal cord injury to study post-lesional respiratory
      neuroplasticity.
AB  - A cervical spinal cord injury induces permanent paralysis, and often leads to
      respiratory distress. To date, no efficient therapeutics have been developed to
      improve/ameliorate the respiratory failure following high cervical spinal cord
      injury (SCI). Here we propose a murine pre-clinical model of high SCI at the
      cervical 2 (C2) metameric level to study diverse post-lesional respiratory
      neuroplasticity. The technique consists of a surgical partial injury at the C2
      level, which will induce a hemiparalysis of the diaphragm due to a
      deafferentation of the phrenic motoneurons from the respiratory centers located
      in the brainstem. The contralateral side of the injury remains intact and allows
      the animal recovery. Unlike other SCIs which affect the locomotor function (at
      the thoracic and lumbar level), the respiratory function does not require animal
      motivation and the quantification of the deficit/recovery can be easily performed
      (diaphragm and phrenic nerve recordings, whole body ventilation). This pre
      clinical C2 SCI model is a powerful, useful, and reliable pre-clinical model to
      study various respiratory and non-respiratory neuroplasticity events at different
      levels (molecular to physiology) and to test diverse putative therapeutic
      strategies which might improve the respiration in SCI patients. 

PMID- 24894021
TI  - Quantification of the activity of tritium produced during the routine synthesis
      of (18)F fluorodeoxyglucose for positron emission tomography.
AB  - Gamma emitting radioactive by-products generated during the cyclotron irradiation
      of (18)O labelled water by protons to produce (18)FDG (fluorodeoxyglucose) for
      positron emission tomography are well characterised. However, the production of
      tritium ((3)H) through the (18)O(p,t)(16)O nuclear reaction has not been
      investigated in detail. The aim of this study was to measure tritium activity
      produced during a large number of (18)FDG production runs in order to obtain a
      better perspective on its impact on radioactive waste management, particularly as
      regards storage and disposal. Tritium was assayed by liquid scintillation
      counting in recovered (18)O water from 24 separate production runs. The mean (SD)
      values of activity and activity concentration were 170 (20) kBq and 81 (8) kBq
      ml(-1) respectively. Both quantities were positively correlated with the activity
      of (18)F. Tritium was detected in much lower concentration in water used to rinse
      the target vessel. The activity of tritium is such that it is exempt from
      regulatory control and may be combined with bulk non-active waste for disposal as
      Very Low Level Waste. However, variations in the irradiation conditions or the
      procedures for the collection of recovered water might result in its
      classification as Low Level Waste, necessitating a more complex disposal regime. 

PMID- 24894023
TI  - Self-assembly and applications of poly(glycidyl methacrylate)s and their
      derivatives.
AB  - In this feature article, we give an overview of the preparation and application
      of self-assembled architectures based on an emerging area of polymers, i.e.,
      poly(glycidyl methacrylate)s (PGMAs) and their derivatives. A series of PGMA
      based aggregates and hybrids, such as micelles, reverse micelles, capsules,
      nanoparticles, and inorganic-organic hybrid materials, has been constructed, and
      diverse morphologies were formed, driven by hydrophobic interactions, hydrogen
      bonding, ionic complexation, host-guest interactions, etc. In particular, the
      assemblies have shown great potential applications as drug vectors, gene vectors,
      solubilizing agents, antimicrobial agent, and so forth. Herein, the general
      guidelines are elaborately selected from literature examples and partially from
      our own. Although still in its infancy, self-assembly of PGMA-based polymers is
      expected to become a hot topic in polymer chemistry and materials science. 

PMID- 24894022
TI  - Combined effect of sesamin and soybean phospholipid on hepatic fatty acid
      metabolism in rats.
AB  - We studied the combined effect of sesamin (1:1 mixture of sesamin and
      episesamine) and soybean phospholipid on lipid metabolism in rats. Male rats were
      fed diets supplemented with 0 or 2 g/kg sesamin, and containing 0 or 50 g/kg
      soybean phospholipid, for 19 days. Sesamin and soybean phospholipid decreased
      serum triacylglycerol concentrations and the combination of these compounds
      further decreased the parameter in an additive fashion. Soybean phospholipid but
      not sesamin reduced the hepatic concentration of triacylglycerol. The combination
      failed to cause a strong decrease in hepatic triacylglycerol concentration,
      presumably due to the up-regulation of Cd36 by sesamin. Combination of sesamin
      and soybean phospholipid decreased the activity and mRNA levels of hepatic
      lipogenic enzymes in an additive fashion. Sesamin strongly increased the
      parameters of hepatic fatty acid oxidation enzymes. Soybean phospholipid
      increased hepatic activity of 3-hydroxyacyl-CoA dehydrogenase although it failed
      to affect the activity of other enzymes involved in fatty acid oxidation. Sesamin
      strongly increased hepatic concentration of carnitine. Sesamin and soybean
      phospholipid combination further increased this parameter, accompanying a
      parallel increase in mRNA expression of carnitine transporter. These changes can
      account for the strong decrease in serum triacylglycerol in rats fed a diet
      containing both sesamin and soybean phospholipid. 

PMID- 24894024
TI  - Trip recovery strategies following perturbations of variable duration.
AB  - Appropriately responding to mechanical perturbations during gait is critical to
      maintain balance and avoid falls. Tripping perturbation onset during swing phase
      is strongly related to the use of different recovery strategies; however, it is
      insufficient to fully explain how strategies are chosen. The dynamic interactions
      between the foot and the obstacle may further explain observed recovery
      strategies but the relationship between such contextual elements and strategy
      selection has not been explored. In this study, we investigated whether
      perturbation onset, duration and side could explain strategy selection for all of
      swing phase. We hypothesized that perturbations of longer duration would elicit
      lowering and delayed-lowering strategies earlier in swing phase than shorter
      perturbations. We developed a custom device to trip subjects multiple times while
      they walked on a treadmill. Seven young, healthy subjects were tripped on the
      left or right side at 10% to 80% of swing phase for 150 ms, 250 ms or 350 ms.
      Strategies were characterized by foot motion post-perturbation and identified by
      an automated algorithm. A multinomial logistic model was used to investigate the
      effect of perturbation onset, side, and the interaction between duration and
      onset on recovery strategy selection. Side perturbed did not affect strategy
      selection. Perturbation duration interacted with onset, limiting the use of
      elevating strategies to earlier in swing phase with longer perturbations. The
      choice between delayed-lowering and lowering strategies was not affected by
      perturbation duration. Although these variables did not fully explain strategy
      selection, they improved the prediction of strategy used in response to tripping
      perturbations throughout swing phase.

PMID- 24894025
TI  - The intubation scoop (i-scoop) - a new type of laryngoscope for difficult and
      normal airways.
AB  - The i-scoop is an intubation device with a curved guiding bar with laterally
      located lenses at its tip, rather than a blade. Twenty-five anaesthesiologists
      intubated a manikin that simulated first a normal and then a difficult airway.
      All participants were able to intubate the difficult airway with a good view of
      the glottis using the i-scoop. None was able to intubate using seven other
      laryngoscopes (Macintosh laryngoscope, GlideScope((r)) GVL and AVL, McGrath((r))
      (Series 5/MAC), C-MAC((r)) , A.P. Advance(TM) ). Intubation was successful only
      with the Airtraq((r)) (n = 10), the Airway Scope (n = 5), the C-MAC D-Blade (n =
      2), the A.P. Advance DAB (n = 1) and the GlideScope DL Trainer (n = 1) (p <
      0.001, success rate of i-scoop vs all 12 laryngoscopes combined). In contrast to
      all other videolaryngoscopes, intubation of the normal airway with the i-scoop
      was achieved even faster than with the Macintosh laryngoscope (p < 0.02). The i
      scoop outperformed all other laryngoscopes in both difficult and normal airways,
      and therefore has potential as an easier and safer alternative to present
      devices.

PMID- 24894027
TI  - Objectively recorded physical activity and the association with gestational
      diabetes.
AB  - The aim of this population-based study was to assess the association between
      objectively recorded physical activity (PA) in early gestation and gestational
      diabetes mellitus (GDM) identified at 28 weeks of gestation in a multi-ethnic
      cohort of healthy pregnant women in Oslo, Norway. In total, 759 women were
      included. In early gestation (<20 weeks), light-, moderate-, and vigorous
      intensity PA and number of steps were objectively recorded (SenseWearTM Armband
      Pro3), and self-reported PA, demographics, and anthropometrics were collected.
      The 75-g oral glucose tolerance test was performed at 28 weeks of gestation.
      Women with GDM had fewer objectively recorded steps (mean 7964 steps/day vs 8879
      steps/day, P < 0.001) and minutes of moderate-to-vigorous-intensity PA (median 62
      min/day vs 75 min/day, P = 0.004) in early gestation than women without GDM.
      Additionally, 30% of women with GDM compared with 44% (P < 0.001) of women
      without GDM self-reported regular PA before pregnancy. The significant inverse
      association between objectively recorded steps per day in early gestation and GDM
      persisted after adjustment for ethnic origin, weeks of gestation, age, parity,
      pre-pregnancy BMI, early life socioeconomic position, and self-reported regular
      PA before pregnancy. The adjusted odds ratio for GDM decreased 19% per standard
      deviation (3159 steps) increase in objectively recorded steps per day (P =
      0.039). Daily life PA in early gestation measured as steps/day was associated
      with lower risk of GDM. 

PMID- 24894026
TI  - A randomized clinical trial of an intervention to relieve thirst and dry mouth in
      intensive care unit patients.
AB  - PURPOSE: To test an intervention bundle for thirst intensity, thirst distress,
      and dry mouth, which are among the most pervasive, intense, distressful,
      unrecognized, and undertreated symptoms in ICU patients, but for which data-based
      interventions are lacking. METHODS: This was a single-blinded randomized clinical
      trial in three ICUs in a tertiary medical center in urban California. A total of
      252 cognitively intact patients reporting thirst intensity (TI) and/or thirst
      distress (TD) scores >=3 on 0-10 numeric rating scales (NRS) were randomized to
      intervention or usual care groups. A research team nurse (RTN#1) obtained
      patients' pre-procedure TI and TD scores and reports of dry mouth. She then
      administered a thirst bundle to the intervention group: oral swab wipes, sterile
      ice-cold water sprays, and a lip moisturizer, or observed patients in the usual
      care group. RTN#2, blinded to group assignment, obtained post-procedure TI and TD
      scores. Up to six sessions per patient were conducted across 2 days. RESULTS:
      Multilevel linear regression determined that the average decreases in TI and TD
      scores from pre-procedure to post-procedure were significantly greater in the
      intervention group (2.3 and 1.8 NRS points, respectively) versus the usual care
      group (0.6 and 0.4 points, respectively) (p < 0.05). The usual care group was 1.9
      times more likely than the intervention group to report dry mouth for each
      additional session on day 1. CONCLUSION: This simple, inexpensive thirst bundle
      significantly decreased ICU patients' thirst and dry mouth and can be considered
      a practice intervention for patients experiencing thirst.

PMID- 24894028
TI  - Uncertainty assessment of imaging techniques for the 3D reconstruction of stent
      geometry.
AB  - This paper presents a quantitative assessment of uncertainty for the 3D
      reconstruction of stents. This study investigates a CP stent (Numed, USA) used in
      congenital heart disease applications with a focus on the variance in
      measurements of stent geometry. The stent was mounted on a model of patient
      implantation site geometry, reconstructed from magnetic resonance images, and
      imaged using micro-computed tomography (CT), conventional CT, biplane fluoroscopy
      and optical stereo-photogrammetry. Image data were post-processed to retrieve the
      3D stent geometry. Stent strut length, separation angle and cell asymmetry were
      derived and repeatability was assessed for each technique along with variation in
      relation to MUCT data, assumed to represent the gold standard. The results
      demonstrate the performance of biplanar reconstruction methods is comparable with
      volumetric CT scans in evaluating 3D stent geometry. Uncertainty on the
      evaluation of strut length, separation angle and cell asymmetry using biplanar
      fluoroscopy is of the order +/-0.2mm, 3 degrees  and 0.03, respectively. These
      results support the use of biplanar fluoroscopy for in vivo measurement of 3D
      stent geometry and provide quantitative assessment of uncertainty in the
      measurement of geometric parameters. 

PMID- 24894029
TI  - Non-intrusive real-time breathing pattern detection and classification for
      automatic abdominal functional electrical stimulation.
AB  - Abdominal Functional Electrical Stimulation (AFES) has been shown to improve the
      respiratory function of people with tetraplegia. The effectiveness of AFES can be
      enhanced by using different stimulation parameters for quiet breathing and
      coughing. The signal from a spirometer, coupled with a facemask, has previously
      been used to differentiate between these breath types. In this study, the
      suitability of less intrusive sensors was investigated with able-bodied
      volunteers. Signals from two respiratory effort belts, positioned around the
      chest and the abdomen, were used with a Support Vector Machine (SVM) algorithm,
      trained on a participant by participant basis, to classify, in real-time,
      respiratory activity as either quiet breathing or coughing. This was compared
      with the classification accuracy achieved using a spirometer signal and an SVM.
      The signal from the belt positioned around the chest provided an acceptable
      classification performance compared to the signal from a spirometer (mean cough
      (c) and quiet breath (q) sensitivity (Se) of Se(c)=92.9% and Se(q)=96.1% vs.
      Se(c)=90.7% and Se(q)=98.9%). The abdominal belt and a combination of both belt
      signals resulted in lower classification accuracy. We suggest that this novel SVM
      classification algorithm, combined with a respiratory effort belt, could be
      incorporated into an automatic AFES device, designed to improve the respiratory
      function of the tetraplegic population. 

PMID- 24894030
TI  - Bioelectric signal detrending using smoothness prior approach.
AB  - Bioelectric signals such as electromyogram (EMG) and electrocardiogram (ECG) are
      often affected by various low-frequency trending interferences. It is critical to
      remove these interferences from the recordings so that the critical features of
      the bioelectric signals could be clearly observed. In this study, an advanced
      method based on smoothness prior approach (SPA) was proposed to solve this
      problem. EMG and ECG signals from both the MIT-BIH database and the experiments
      were employed to evaluate the detrending performance of the proposed method. For
      comparison purposes, a conventional high-pass Butterworth filter was also used
      for the detrending of the EMG and ECG signals. Two numerical measures, the
      correlation coefficient (CC) and root mean square error (RMSE) between the clean
      data and the detrended data, were calculated to evaluate the detrending
      performance. The results showed that the proposed SPA method outperformed the
      high-pass filtering method in reducing various kinds of trending interferences
      and preserving the desired frequency contents of the EMG and ECG signals. The
      study suggested that the SPA method might be a promising approach in detrending
      bioelectric signals. 

PMID- 24894031
TI  - Influence of 3D QCT scan protocol on the QCT-based finite element models of human
      vertebral cancellous bone.
AB  - Quantitative computed tomography (QCT)-based finite element (FE) models provide a
      better prediction of vertebral strength than dual-energy X-ray absorptiometry.
      However, FE models are often created from datasets acquired at different CT scan
      protocols and it is unclear whether this influences the FE results. The aim of
      this paper was to investigate whether there was an effect of the CT scan protocol
      on the FE models. 12 human thoracolumbar vertebrae were scanned on top of a
      calcium hydroxyapatite calibration phantom using a standard QCT scan protocol -
      120kV, 100mAs (PA); and a low dose protocol - 90kV, 150mAs (PB). FE cancellous
      models with cuboid volume of interest and inhomogeneous nonlinear bone properties
      were created. Axial compression was simulated. The apparent BMD, modulus and
      yield strength showed significant differences between the two scan protocols. The
      apparent BMD, the modulus and yield strength between the two groups were highly
      linearly correlated. This paper indicated that the FE models created from image
      datasets acquired at different X-ray tube voltage settings would give
      significantly different results and this effect could be possibly corrected using
      a linear correction approach. 

PMID- 24894032
TI  - Automation of a portable extracorporeal circulatory support system with adaptive
      fuzzy controllers.
AB  - The presented work relates to the procedure followed for the automation of a
      portable extracorporeal circulatory support system. Such a device may help
      increase the chances of survival after suffering from cardiogenic shock outside
      the hospital, additionally a controller can provide of optimal organ perfusion,
      while reducing the workload of the operator. Animal experiments were carried out
      for the acquisition of haemodynamic behaviour of the body under extracorporeal
      circulation. A mathematical model was constructed based on the experimental data,
      including a cardiovascular model, gas exchange and the administration of
      medication. As the base of the controller fuzzy logic was used allowing the easy
      integration of knowledge from trained perfusionists, an adaptive mechanism was
      included to adapt to the patient's individual response. Initial simulations show
      the effectiveness of the controller and the improvements of perfusion after
      adaptation. 

PMID- 24894033
TI  - A new paradigm of electrical stimulation to enhance sensory neural function.
AB  - The ability to improve peripheral neural transmission would have significant
      therapeutic potential in medicine. A technology of this kind could be used to
      restore and/or enhance sensory function in individuals with depressed sensory
      function, such as older adults or patients with peripheral neuropathies. The goal
      of this study was to investigate if a new paradigm of subsensory electrical noise
      stimulation enhances somatosensory function. Vibration (50Hz) was applied with a
      Neurothesiometer to the plantar aspect of the foot in the presence or absence of
      subsensory electrical noise (1/f type). The noise was applied at a proximal site,
      on a defined region of the tibial nerve path above the ankle. Vibration
      perception thresholds (VPT) of younger adults were measured in control and
      experimental conditions, in the absence or presence of noise respectively. An
      improvement of ~16% in VPT was found in the presence of noise. These are the
      first data to demonstrate that modulation of axonal transmission with externally
      applied electrical noise improves perception of tactile stimuli in humans. 

PMID- 24894035
TI  - Publishing trauma-related topics in ANZ Journal of Surgery.

PMID- 24894034
TI  - Prevalence and risk factors for retinopathy in persons without diabetes: the
      Singapore Indian Eye Study.
AB  - PURPOSE: To describe prevalence and risk factors for retinopathy in an Asian
      Indian population without diabetes. METHODS: A population-based cross-sectional
      study of 3400 Indians aged 40-80 years residing in Singapore was conducted.
      Retinopathy was assessed from retinal photographs by trained graders using
      modified Airlie House Classification System. Risk factors were assessed from
      standardized interviews, clinical examinations and laboratory investigations.
      Diabetes mellitus was defined as glycosylated haemoglobin >=6.5%, use of diabetic
      medication or physician diagnosis of diabetes. RESULTS: Among the 1900
      individuals without diabetes, mean HbA1c was 5.7% and mean systolic blood
      pressure was 132.4 mmHg. Age-standardized prevalence of retinopathy was 5.05% (n
      = 98; 95% confidence interval [CI], 4.07-6.21), with no significant difference in
      retinopathy prevalence between males (6.15%) and females (4.13%). Among non
      diabetic persons with retinopathy, 96.9% (n = 95) had signs of minimal-to-mild
      retinopathy while 3.06% (n = 3) had moderate-to-severe retinopathy. After
      adjusting for multiple covariables, retinopathy signs were associated with higher
      levels of HbA1c (odds ratio [OR], 2.4; 95% CI, 1.3-4.5; per% increase), systolic
      blood pressure (OR, 1.02; 95% CI, 1.01-1.03; per mmHg increase) and serum
      creatinine (OR, 1.005; 95% CI, 1.002-1.009; per mm increase), but not C-reactive
      protein, cigarette smoking or lipid levels. CONCLUSION: One in 20 Asian Indian
      persons without diabetes had retinopathy signs. Risk factors for these signs
      include higher glycosylated haemoglobin, systolic blood pressure and serum
      creatinine.

PMID- 24894036
TI  - Surgeons of the future: where will they come from?

PMID- 24894037
TI  - Nuclear reprogramming and induced pluripotent stem cells: a review for surgeons.
AB  - Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the
      exogenous expression of defined transcription factors. iPSCs share the defining
      features of embryonic stem cells (ESCs) in that they are able to self renew
      indefinitely and maintain the potential to develop into all cell types of the
      body. These cells have key advantages over ESCs in that they are autologous to
      the donor cells and can be generated from individuals at any age. iPSCs also
      circumvent ethical and political issues surrounding the destruction of embryos
      that is necessary in the isolation of ESCs. This review briefly describes the
      advent of iPSC technology and the concepts of nuclear reprogramming, and
      discusses the potential application of this powerful biological tool in both
      surgical research and regenerative medicine.

PMID- 24894038
TI  - Pedicled dartos flap interposition in rectourethral fistula repair.

PMID- 24894039
TI  - Beware of NSAID abuse: think twice before operating!

PMID- 24894040
TI  - The keystone flap: is your 'unclosable' wound really unclosable?

PMID- 24894041
TI  - Actinomycosis of the rectum mimicking a malignant neoplasm.

PMID- 24894042
TI  - A Role for CHH Methylation in the Parent-of-Origin Effect on Altered Circadian
      Rhythms and Biomass Heterosis in Arabidopsis Intraspecific Hybrids.
AB  - Hybrid plants and animals often show increased levels of growth and fitness, a
      phenomenon known as hybrid vigor or heterosis. Circadian rhythms optimize
      physiology and metabolism in plants and animals. In plant hybrids and polyploids,
      expression changes of the genes within the circadian regulatory network, such as
      CIRCADIAN CLOCK ASSOCIATED1 (CCA1), lead to heterosis. However, the relationship
      between allelic CCA1 expression and heterosis has remained elusive. Here, we show
      a parent-of-origin effect on altered circadian rhythms and heterosis in
      Arabidopsis thaliana F1 hybrids. This parent-of-origin effect on biomass
      heterosis correlates with altered CCA1 expression amplitudes, which are
      associated with methylation levels of CHH (where H = A, T, or C) sites in the
      promoter region. The direction of rhythmic expression and hybrid vigor is
      reversed in reciprocal F1 crosses involving mutants that are defective in the RNA
      directed DNA methylation pathway (argonaute4 and nuclear RNA polymerase D1a) but
      not in the maintenance methylation pathway (methyltransferase1 and decrease in
      DNA methylation1). This parent-of-origin effect on circadian regulation and
      heterosis is established during early embryogenesis and maintained throughout
      growth and development.

PMID- 24894043
TI  - The bHLH142 Transcription Factor Coordinates with TDR1 to Modulate the Expression
      of EAT1 and Regulate Pollen Development in Rice.
AB  - Male sterility plays an important role in F1 hybrid seed production. We
      identified a male-sterile rice (Oryza sativa) mutant with impaired pollen
      development and a single T-DNA insertion in the transcription factor gene
      bHLH142. Knockout mutants of bHLH142 exhibited retarded meiosis and defects in
      tapetal programmed cell death. RT-PCR and in situ hybridization analyses showed
      that bHLH142 is specifically expressed in the anther, in the tapetum, and in
      meiocytes during early meiosis. Three basic helix-loop-helix transcription
      factors, UDT1 (bHLH164), TDR1 (bHLH5), and EAT1/DTD1 (bHLH141) are known to
      function in rice pollen development. bHLH142 acts downstream of UDT1 and GAMYB
      but upstream of TDR1 and EAT1 in pollen development. In vivo and in vitro assays
      demonstrated that bHLH142 and TDR1 proteins interact. Transient promoter assays
      demonstrated that regulation of the EAT1 promoter requires bHLH142 and TDR1.
      Consistent with these results, 3D protein structure modeling predicted that
      bHLH142 and TDR1 form a heterodimer to bind to the EAT1 promoter. EAT1 positively
      regulates the expression of AP37 and AP25, which induce tapetal programmed cell
      death. Thus, in this study, we identified bHLH142 as having a pivotal role in
      tapetal programmed cell death and pollen development.

PMID- 24894044
TI  - Meta-Analysis of Arabidopsis thaliana Phospho-Proteomics Data Reveals
      Compartmentalization of Phosphorylation Motifs.
AB  - Protein (de)phosphorylation plays an important role in plants. To provide a
      robust foundation for subcellular phosphorylation signaling network analysis and
      kinase-substrate relationships, we performed a meta-analysis of 27 published and
      unpublished in-house mass spectrometry-based phospho-proteome data sets for
      Arabidopsis thaliana covering a range of processes, (non)photosynthetic tissue
      types, and cell cultures. This resulted in an assembly of 60,366 phospho-peptides
      matching to 8141 nonredundant proteins. Filtering the data for quality and
      consistency generated a set of medium and a set of high confidence phospho
      proteins and their assigned phospho-sites. The relation between single and
      multiphosphorylated peptides is discussed. The distribution of p-proteins across
      cellular functions and subcellular compartments was determined and showed
      overrepresentation of protein kinases. Extensive differences in frequency of pY
      were found between individual studies due to proteomics and mass spectrometry
      workflows. Interestingly, pY was underrepresented in peroxisomes but
      overrepresented in mitochondria. Using motif-finding algorithms motif-x and MMFPh
      at high stringency, we identified compartmentalization of phosphorylation motifs
      likely reflecting localized kinase activity. The filtering of the data assembly
      improved signal/noise ratio for such motifs. Identified motifs were linked to
      kinases through (bioinformatic) enrichment analysis. This study also provides
      insight into the challenges/pitfalls of using large-scale phospho-proteomic data
      sets to nonexperts.

PMID- 24894046
TI  - Co-morbidities and mortality associated with intracranial bleeds and ischaemic
      stroke.
AB  - Stroke is a leading cause of mortality and acquired disability; however, there
      has been no comprehensive comparison of co-morbid risk factors between different
      stroke subtypes. The aim of this study was to compare risk factors and mortality
      for subdural haematoma (SDH), subarachnoid haemorrhage (SAH) and ischaemic and
      haemorrhagic stroke. We compiled a database of all patients admitted with these
      conditions to a large teaching hospital in Birmingham, United Kingdom during the
      period 2000-2007 using the International Classification of Disease (ICD) 10th
      revision codes. Generalised linear models were constructed to calculate relative
      risks (RRs) associated with co-morbidities. In total, 4804 patients were admitted
      with diagnoses of SDH (1004), SAH (807), ischaemic stroke (2579) and haemorrhagic
      stroke (414). Patients with SDH were less likely to have pneumonia (0.492, 95%
      CI, 0.330-0.734; p < 0.001), whereas alcohol abuse (4.21, 95% CI, 2.82-6.28; p <
      0.001) was more common. In SAH, ischaemic heart disease (0.56, 95% CI, 0.40-0.79;
      p < 0.001) was less common. As expected, a range of cardiovascular risk factors
      were associated with ischaemic stroke. Epilepsy was positively associated with
      ischaemic stroke (1.94, 95% CI, 1.36-2.76; p < 0.001), indicating a role for
      targeted primary prevention in patients with epilepsy. Five-year survival was
      lower in ischaemic and haemorrhagic strokes (41% and 40% respectively, vs. 73% in
      SDH and 64% in SAH; p < 0.001). These findings may guide clinical risk
      stratification, and improve the prognostic information given to patients. 

PMID- 24894047
TI  - Hypertension alters phosphorylation of VASP in brain endothelial cells.
AB  - Hypertension impairs cerebral vascular function. Vasodilator-stimulated
      phosphoprotein (VASP) mediates active reorganization of the cytoskeleton via
      membrane ruffling, aggregation and tethering of actin filaments. VASP regulation
      of endothelial barrier function has been demonstrated by studies using VASP(-/-)
      animals under conditions associated with tissue hypoxia. We hypothesize that
      hypertension regulates VASP expression and/or phosphorylation in endothelial
      cells, thereby contributing to dysfunction in the cerebral vasculature. Because
      exercise has direct and indirect salutary effects on vascular systems that have
      been damaged by hypertension, we also investigated the effect of exercise on
      maintenance of VASP expression and/or phosphorylation. We used
      immunohistochemistry, Western blotting and immunocytochemistry to examine the
      effect of hypertension on VASP expression and phosphorylation in brain
      endothelial cells in normotensive [Wistar-Kyoto (WKY)] and spontaneously
      hypertensive (SH) rats under normal and exercise conditions. In addition, we
      analyzed VASP regulation in normoxia- and hypoxia-induced endothelial cells.
      Brain endothelial cells exhibited significantly lower VASP immunoreactivity and
      phosphorylation at the Ser157 residue in SHR versus WKY rats. Exercise reversed
      hypertension-induced alterations in VASP phosphorylation. Western blotting and
      immunocytochemistry indicated reduction in VASP phosphorylation in hypoxic versus
      normoxic endothelial cells. These results suggest that diminished VASP expression
      and/or Ser157 phosphorylation mediates endothelial changes associated with
      hypertension and exercise may normalize these changes, at least in part, by
      restoring VASP phosphorylation. 

PMID- 24894049
TI  - Prevalence of essential tremor in an idiopathic Parkinson's disease patient
      population.
AB  - Essential tremor (ET) and Parkinson's disease (PD) tremor differ in type,
      frequency and distribution. Despite being two separate disorders, there have been
      cases reported of comorbidity for ET-PD. Studies have reported an increase in the
      incidence of ET in relatives of patients with PD, yet the risk of developing PD
      in ET patients has not been thoroughly investigated. Our study set out to
      determine the incidence of precedent ET in PD patients. We conducted a
      retrospective chart review analysis of 332 idiopathic PD patients to determine
      how many of them had ET prior to the diagnosis of PD and the percentage of them
      who were also diagnosed with ET. Our results indicate that the prevalence of
      precedent ET among a population of idiopathic PD patients was not any higher than
      the prevalence of ET in a comparable general population. Our results support the
      notion that ET and PD are mutually independent disorders. Further studies are
      needed to understand the exact relationship between these two disorders. 

PMID- 24894048
TI  - Dairy intake is associated with memory and pulsatility index in heart failure.
AB  - PURPOSE/AIM: Past work shows an inconsistent relationship between dairy intake
      and cognition in healthy older adults. A cross-sectional design was conducted to
      examine dairy consumption, cognitive dysfunction, and cerebral blood flow in a
      sample of older adults with heart failure (HF) to clarify their association in
      this population at high risk for adverse neurocognitive outcomes. MATERIALS AND
      METHODS: A total of 86 older adults with HF (70.39 +/- 9.51 years; 33.1% female)
      underwent neuropsychological testing, transcranial Doppler (TCD) sonography to
      quantify cerebral blood flow. Dairy intake was quantified using a brief self
      report questionnaire. RESULTS: Partial correlations between the dairy consumption
      questionnaire and neuropsychological tests were conducted adjusting for HF
      severity, age, and sex. Contrary to expectations, results showed greater dairy
      intake was associated with poorer memory (r = -0.21, p = 0.01) and higher
      pulsatility index in the medial cerebral artery (r = -0.17, p = 0.05).
      CONCLUSION: Results suggest that greater dairy intake was associated with poorer
      memory performance in older adults with HF. Several possible explanations for
      these findings exist, including the contribution of high-fat dairy to underlying
      physiological processes that promote vascular cognitive impairment. Prospective
      studies employing objective measures specific to high and low fat dairy are
      needed to clarify this possibility.

PMID- 24894050
TI  - Conducting research during disasters.
AB  - The potential for man-made or natural disasters is a reality that exists within
      the confines of the global setting. Man-made and/or natural disasters, although
      devastating to the human population, offers researchers the ability to explore
      and advance current preparedness, response, and recovery practices. When
      conducting research, consideration must be given to the ethical treatment of
      vulnerable populations and the protection of privacy for those affected by the
      disaster. 

PMID- 24894051
TI  - Nursing leadership in disaster preparedness and response.
AB  - Nurses serve as leaders in disaster preparedness and response at multiple levels:
      within their own homes and neighborhoods, at disaster scenes, and the workplace,
      which can vary from a health care facility, in the community, or at the state,
      national, or international level. This chapter provides an overview on theories
      of leadership with a historical context for nursing leadership; setting the
      context for nursing leadership in disaster preparedness and response. Although
      few research studies exist, there are numerous examples of nurses who provide
      leadership for disaster preparedness and response. To define the current state of
      the science, the research studies cited in this chapter are supplemented with
      case studies from particular disasters. The major finding of this review is that
      nursing leadership in disaster preparedness and response is a field of study that
      needs to be developed. 

PMID- 24894052
TI  - Conducting ethically sound disaster nursing research.
AB  - Health care professionals have always faced the threat of catastrophic disaster
      and pandemic infectious illness but have continued to practice without adequately
      considering the ethical consequences of many of the decision-making tools we
      currently have in place. Lack of research on these ethical decisions in the face
      of disasters regarding the 3Rs-rationing (triage and allocating scarce
      resources), restrictions (quarantine and the denial of care based on some
      criteria or the magnitude of the disaster), and responsibility (duty to treat and
      duty to report for work)-will leave nurses to make decisions in the throws of
      disaster rather than before the crisis occurs. This chapter focuses on conducting
      ethically sound nursing research in disasters. A survey of the literature on the
      topic to include current research on the 3Rs, frameworks, and methodological
      problems will be examined. This chapter concludes with a call to action for the
      nursing profession to accept their role as patient advocates and drive the
      research necessary to avoid the ethical pitfalls seen in recent disaster
      decisions and scenarios. 

PMID- 24894053
TI  - Legal issues in emergency response.
AB  - During disasters, health care providers are faced with limited resources, harsh
      environments, and an increased amount of sick and injured patients. These
      conditions sometimes require health care providers to deviate from existing
      treatment protocols. Deviating from these protocols results in a perception of
      increased legal risk for health care providers. This has led to a national debate
      regarding the necessity of establishing altered standards of care for health care
      providers during crisis events. This chapter explores the development of disaster
      preparedness, the issue of health care provider liability, and national and local
      efforts to protect providers in disaster situations. 

PMID- 24894045
TI  - Systems Analysis of the Response of Photosynthesis, Metabolism, and Growth to an
      Increase in Irradiance in the Photosynthetic Model Organism Chlamydomonas
      reinhardtii.
AB  - We investigated the systems response of metabolism and growth after an increase
      in irradiance in the nonsaturating range in the algal model Chlamydomonas
      reinhardtii. In a three-step process, photosynthesis and the levels of
      metabolites increased immediately, growth increased after 10 to 15 min, and
      transcript and protein abundance responded by 40 and 120 to 240 min,
      respectively. In the first phase, starch and metabolites provided a transient
      buffer for carbon until growth increased. This uncouples photosynthesis from
      growth in a fluctuating light environment. In the first and second phases, rising
      metabolite levels and increased polysome loading drove an increase in fluxes.
      Most Calvin-Benson cycle (CBC) enzymes were substrate-limited in vivo, and
      strikingly, many were present at higher concentrations than their substrates,
      explaining how rising metabolite levels stimulate CBC flux. Rubisco, fructose-1,6
      biosphosphatase, and seduheptulose-1,7-bisphosphatase were close to substrate
      saturation in vivo, and flux was increased by posttranslational activation. In
      the third phase, changes in abundance of particular proteins, including increases
      in plastidial ATP synthase and some CBC enzymes, relieved potential bottlenecks
      and readjusted protein allocation between different processes. Despite reasonable
      overall agreement between changes in transcript and protein abundance (R2 =
      0.24), many proteins, including those in photosynthesis, changed independently of
      transcript abundance.

PMID- 24894054
TI  - Psychological impact of disasters on communities.
AB  - Disaster mental health is defined as "community and individual mental and
      behavioral health preparedness and response as well as other psychosocial and
      cultural factors" (Hoffman et al., 2005, p. S141). The research included in this
      review was published between 2000 and 2011, capturing a snapshot of the last
      decade of relevant research on the psychological impact of disaster. The
      conceptual framework used to examine the research involves a population-based
      approach based on primary, secondary, and tertiary prevention levels. Aspects of
      conducting mental health research, to include evidence-based approaches and
      disaster mental health outcome measurements postdisaster, are also included. The
      authors conclude the review by presenting implications and future recommendations
      for nursing practice and research related to the psychological impact of
      disasters on communities. 

PMID- 24894055
TI  - Reconsidering "special needs" populations during a disaster.
AB  - Meeting the "special needs" of at-risk populations affected by disasters is of
      the utmost importance. In the United States, there are 54 million people who fit
      into the special needs category who are defined as handicapped, disabled,
      vulnerable, challenged, or having special needs. The paramount importance for the
      special needs population is maintaining human dignity throughout the disaster
      management cycle. Government agencies, nongovernmental organizations, and
      advocacy organizations have all worked together to attempt to address and ensure
      that the needs of all individuals are addressed throughout the disaster cycle.
      Each provider and emergency responder should be familiar with the Americans with
      Disabilities Act requirements, but this alone does not begin to address the needs
      of children, the elderly, or other individuals and their special needs. There are
      multiple theoretical frameworks that may be useful, but the most human approach
      may be to consider needs based on Maslow's hierarchy of needs. 

PMID- 24894056
TI  - The role of technology and informatics in disaster planning and response.
AB  - It is clear that technology and informatics are becoming increasingly important
      in disasters and humanitarian response. Technology is a critical tool to
      recording, analyzing, and predicting trends in data that could not be achieved
      prior to its implementation. Informatics is the translation of this data into
      information, knowledge, and wisdom. Combining technology and informatics
      applications with response efforts has resulted in various enhanced
      biosurveillance efforts, advanced communications, and information management
      during disasters. Although these efforts have been well described in the
      literature, research on the impact of technology and informatics during these
      efforts has been limited. As a result, this chapter will provide an overview of
      these technology and informatics solutions and present suggestions for further
      research in an era when disaster and humanitarian response efforts continue to
      increase as well. A literature search was performed using PubMed search tools
      with the National Library of Medicine Medical Subject Headings (MeSH) terms of
      "disasters," "disaster planning," "disaster medicine," "technology,"
      "informatics," and "research." Search limitations were set for 5 years and in
      English. Because of the limited number of research articles in this field, the
      MeSH term research was deleted. 

PMID- 24894057
TI  - Update on competencies and education.
AB  - The beginning of the 21st century has been marked by an increase in attention to
      the quality of emergency and disaster response, particularly the preparedness of
      health workers of all kinds. The increase in natural disasters, civil unrest, and
      dislocation of populations has seen health workers mobilized. These workers are
      moving, both within countries and across borders, as members of long- organized
      teams such as the National Disaster Medical System (NDMS), volunteers joining
      through a nongovernmental organization (NGO) such as a Red Cross/Red Crescent
      unit, or individuals self-deploying to the scene of the emergency. Postevent
      evaluations have consistently identified the need for those responding to be able
      to join in an organized response that includes taking on assigned roles,
      communication through established channels and minimization of the number of
      "SUVs" or "spontaneous unrequested volunteers." Although bystanders and self
      deployed helpers (some with professional qualifications) are the first at any
      disastrous event, the subsequent response efforts are expected to be organized,
      efficient, and effective. This requires advance training of the responders. 

PMID- 24894058
TI  - Willingness, ability, and intentions of health care workers to respond.
AB  - Health care workers (HCWs) are a critical component of the emergency management
      cycle (prevention, mitigation, preparation, response, and recovery). The
      potential for large numbers of injured from either a man-made or natural disaster
      has resulted in the development of surge capacity plans and attempts to predict
      how many HCWs will be available to respond. Since 1991 (with the majority of the
      research published in 2002 and later), researchers have been conducting studies
      to learn about the willingness, ability, and intentions of HCWs to respond to
      disasters. Potential and real barriers to disaster response are being explored as
      well. This chapter focuses on research authored or coauthored by nurses. Nurse
      authored research is just a portion of the growing body of knowledge in this
      area; however, the findings are consistent with other published works. HCWs are
      more likely to be willing and able to respond to natural disasters and less
      likely to be willing and able during infectious outbreaks or incidents with
      potential exposure to harmful agents (biological, chemical, nuclear, or
      radiological). HCW concerns include safety of self and family, availability of
      protective equipment, medicines and vaccines, and caretaking responsibilities
      (children, elders, and pets). 

PMID- 24894059
TI  - International disaster humanitarian assistance for nurses.
AB  - Nurses participate in humanitarian assistance following disasters throughout the
      world. Many have limited training or experience in this type of humanitarian aid.
      This chapter provides an overview and foundation of international humanitarian
      assistance for nurses to build upon to strengthen their participation in and
      contribution to these efforts. There is a growing sophistication and coordination
      of humanitarian assistance across many organizations and governments. This
      chapter reviews the research and resources that promote nurse participation in
      international disaster humanitarian assistance. 

PMID- 24894062
TI  - Confocal imaging of confined quiescent and flowing colloid-polymer mixtures.
AB  - The behavior of confined colloidal suspensions with attractive interparticle
      interactions is critical to the rational design of materials for directed
      assembly(1-3), drug delivery(4), improved hydrocarbon recovery(5-7), and flowable
      electrodes for energy storage(8). Suspensions containing fluorescent colloids and
      non-adsorbing polymers are appealing model systems, as the ratio of the polymer
      radius of gyration to the particle radius and concentration of polymer control
      the range and strength of the interparticle attraction, respectively. By tuning
      the polymer properties and the volume fraction of the colloids, colloid fluids,
      fluids of clusters, gels, crystals, and glasses can be obtained(9). Confocal
      microscopy, a variant of fluorescence microscopy, allows an optically transparent
      and fluorescent sample to be imaged with high spatial and temporal resolution in
      three dimensions. In this technique, a small pinhole or slit blocks the emitted
      fluorescent light from regions of the sample that are outside the focal volume of
      the microscope optical system. As a result, only a thin section of the sample in
      the focal plane is imaged. This technique is particularly well suited to probe
      the structure and dynamics in dense colloidal suspensions at the single-particle
      scale: the particles are large enough to be resolved using visible light and
      diffuse slowly enough to be captured at typical scan speeds of commercial
      confocal systems(10). Improvements in scan speeds and analysis algorithms have
      also enabled quantitative confocal imaging of flowing suspensions(11-16,37). In
      this paper, we demonstrate confocal microscopy experiments to probe the confined
      phase behavior and flow properties of colloid-polymer mixtures. We first prepare
      colloid-polymer mixtures that are density- and refractive-index matched. Next, we
      report a standard protocol for imaging quiescent dense colloid-polymer mixtures
      under varying confinement in thin wedge-shaped cells. Finally, we demonstrate a
      protocol for imaging colloid-polymer mixtures during microchannel flow.

PMID- 24894061
TI  - Antigen delivery by lipid-enveloped PLGA microparticle vaccines mediated by in
      situ vesicle shedding.
AB  - Lipid-coated poly(lactide-co-glycolide) microparticles (LCMPs) consist of a solid
      polymer core wrapped by a surface lipid bilayer. Previous studies demonstrated
      that immunization with LCMPs surface-decorated with nanograms of antigen elicit
      potent humoral immune responses in mice. However, the mechanism of action for
      these vaccines remained unclear, as LCMPs are too large to drain efficiently to
      lymph nodes from the vaccination site. Here, we characterized the stability of
      the lipid envelope of LCMPs and discovered that in the presence of serum the
      lipid coating of the particles spontaneously delaminates, shedding antigen
      displaying vesicles. Lipid delamination generated 180 nm liposomes in a
      temperature- and lipid/serum-dependent manner. Vesicle shedding was restricted by
      inclusion of high-TM lipids or cholesterol in the LCMP coating. Administration of
      LCMPs bearing stabilized lipid envelopes generated weaker antibody responses than
      those of shedding-competent LCMPs, suggesting that in situ release of antigen
      loaded vesicles plays a key role in the remarkable potency of LCMPs as vaccine
      adjuvants. 

PMID- 24894063
TI  - Enhancing Research Ethics Review Systems in Egypt: The Focus of an International
      Training Program Informed by an Ecological Developmental Approach to Enhancing
      Research Ethics Capacity.
AB  - Recently, training programs in research ethics have been established to enhance
      individual and institutional capacity in research ethics in the developing world.
      However, commentators have expressed concern that the efforts of these training
      programs have placed 'too great an emphasis on guidelines and research ethics
      review', which will have limited effect on ensuring ethical conduct in research.
      What is needed instead is a culture of ethical conduct supported by national and
      institutional commitment to ethical practices that are reinforced by upstream
      enabling conditions (strong civil society, public accountability, and trust in
      basic transactional processes), which are in turn influenced by developmental
      conditions (basic freedoms of political freedoms, economic facilities, social
      opportunities, transparency guarantees, and protective security). Examining this
      more inclusive understanding of the determinants of ethical conduct enhances at
      once both an appreciation of the limitations of current efforts of training
      programs in research ethics and an understanding of what additional training
      elements are needed to enable trainees to facilitate national and institutional
      policy changes that enhance research practices. We apply this developmental model
      to a training program focused in Egypt to describe examples of such additional
      training activities. 

PMID- 24894066
TI  - Vibrational relaxation of O3(nu2) by O((3)P).
AB  - Laboratory measurements of the rate coefficient for quenching of O3(nu2) by
      ground-state atomic oxygen, kO(nu2), at room temperature are presented. kO(nu2)
      is currently not well known and is necessary for appropriate nonlocal
      thermodynamic equilibrium modeling of the upper mesosphere and lower
      thermosphere. In this work, a 266 nm laser pulse photolyzes a small amount of O3
      in a slow-flowing gas mixture of O3, Xe, and Ar. This process simultaneously
      produces atomic oxygen and increases the temperature of the gas mixture slightly,
      thereby increasing the population in the O3(nu2) state. Transient diode laser
      absorption spectroscopy is used to monitor the populations of the O3(nu2) and
      ground vibrational states as the system re-equilibrates. Relaxation rates are
      measured over a range of quencher concentrations to extract the rate coefficient
      of interest. The value of kO(nu2) was determined to be (2.2 +/- 0.5) * 10(-12)
      cm(3) s(-1). 

PMID- 24894068
TI  - Automated bone marrow analysis in rats--a change in paradigm in toxicologic
      clinical pathology?

PMID- 24894064
TI  - Advances in therapy for pediatric sarcomas.
AB  - Pediatric sarcomas are relatively rare malignancies individually. As a group they
      are typically approached with combination chemotherapies in addition to local
      control. Fortunately, these malignancies have been approached through careful
      clinical trial collaboration to define risk groups and appropriately deliver
      local control measures and systemic therapies. Although local disease is
      typically approached with curative intent, therapy typically lasts over 6 months
      and has significant associated morbidities. It is more difficult to cure
      metastatic disease or induce sustained remissions. In this article, we discuss
      recent advances in the understanding of the disease process and highlight recent
      and future cooperative group trials in osteosarcoma, Ewing sarcoma,
      rhabdomyosarcoma, nonrhabdomyosarcoma soft tissue sarcomas, and desmoid tumor as
      well as discuss promising therapeutic approaches such as epigenetics and
      immunotherapy.

PMID- 24894067
TI  - Efficient extraction of olive pulp and stone proteins by using an enzyme-assisted
      method.
AB  - An efficient protein extraction protocol for proteins from olive pulp and stone
      by using enzymes was developed. For this purpose, different parameters that
      affect the extraction process, such as enzyme type and content, pH, and
      extraction temperature and time, were tested. The influence of these factors on
      protein recovery was examined using the standard Bradford assay, while the
      extracted proteins were characterized by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE). The best extraction conditions were achieved at
      pH 7.0 and 5% (v/v) Palatase(r) 20000 L (lipase) for pulp and Lecitase(r) Ultra
      (phospholipase) for stone proteins. The optimal extraction temperature and time
      were 30 and 40  degrees C for 15 min for pulp and stone tissues, respectively.
      Under these conditions, several protein extracts coming from olive fruits of
      different genetic variety were analyzed, their profiles being compared by SDS
      PAGE. The developed enzyme-assisted extraction method showed faster extraction,
      higher recovery, and reduced solvent usage than the nonenzymatic methods
      previously described in the literature. In the case of stone proteins, different
      electrophoretic profiles and band intensities were obtained that could be helpful
      to distinguish samples according to their genetic variety. 

PMID- 24894065
TI  - Phthalates and diet: a review of the food monitoring and epidemiology data.
AB  - Phthalates are associated with a variety of health outcomes, but sources that may
      be targeted for exposure reduction messaging remain elusive. Diet is considered a
      significant exposure pathway for these compounds. Therefore, we sought to
      identify primary foods associated with increased exposure through a review of the
      food monitoring survey and epidemiological data. A search in PubMed and Google
      Scholar for keywords "phthalates" and "diet" "food" "food stuffs" "dietary
      intake" "food intake" and "food concentration" resulted in 17 studies measuring
      phthalate concentrations in United States (US) and international foods, three
      epidemiological association studies, and three interventions. We report on food
      groups with high (>=300 MUg/kg) and low (<50 MUg/kg) concentrations and compare
      these to foods associated with phthalate body burden. Based on these data, we
      estimated daily intakes of di-2-ethylhexyl phthalate (DEHP) of US women of
      reproductive age, adolescents and infants for typical consumption patterns as
      well as healthy and poor diets. We consistently observed high DEHP concentrations
      in poultry, cooking oils and cream-based dairy products (>=300 MUg/kg) across
      food monitoring studies. Diethyl phthalate (DEP) levels were found at low
      concentrations across all food groups. In line with these data, epidemiological
      studies showed positive associations between consumption of meats, discretionary
      fat and dairy products and DEHP. In contrast to food monitoring data, DEP was
      found to be associated with intake of vegetables in two studies. DEHP exposure
      estimates based on typical diets were 5.7, 8.1, and 42.1 MUg/kg-day for women of
      reproductive age, adolescents and infants, respectively, with dairy as the
      largest contributor to exposure. Diets high in meat and dairy consumption
      resulted in two-fold increases in exposure. Estimates for infants based on a
      typical diet exceeded the Environmental Protection Agency's reference dose of 20
      MUg/kg-day while diets high in dairy and meat consumed by adolescents also
      exceeded this threshold. The review of the literature demonstrated that DEHP in
      some meats, fats and dairy products is consistently found in high concentrations
      and can contribute to exposure. Guidance on future research in this area is
      provided that may help to identify methods to reduce dietary phthalate exposures.

PMID- 24894069
TI  - Diatoms in cytologic specimens of aquatic animals. Part I, fecal samples.

PMID- 24894070
TI  - Relationship between urinary Tamm-Horsfall protein excretion and renal function
      in dogs with naturally occurring renal disease.
AB  - BACKGROUND: Tamm-Horsfall protein (THP) is physiologically excreted in urine, but
      little is known about the role of THP in the diagnosis of renal disease in dogs.
      OBJECTIVE: The aim of this study was to evaluate to which extent naturally
      occurring renal disease affects the urinary excretion of THP. METHODS: Dogs were
      divided into 5 groups according to plasma creatinine concentration, urinary
      protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P
      ClCr ) rates: Group A (healthy control dogs; n = 8), nonazotemic and
      nonproteinuric dogs, with P-ClCr rates > 90 mL/min/m(2) ; group B (n = 25),
      nonazotemic and nonproteinuric dogs with reduced P-ClCr rates (51-89 mL/min/m(2)
      ); group C (n = 7), nonazotemic but proteinuric dogs with P-ClCr rates 53-98
      mL/min/m(2) ; group D (n = 8), azotemic and borderline proteinuric dogs (P-ClCr
      rates: 22-45 mL/min/m(2) ); and group E (n = 15), azotemic and proteinuric dogs
      (not tested for P-ClCr ). THP was measured by quantitative Western blot analysis,
      and the ratio of THP-to-urinary creatinine (THP/UC) was calculated. RESULTS: The
      THP/UC concentrations were not different among dogs of groups A-D, but were
      reduced in dogs of group E (P < .001). THP/UC correlated negatively with serum
      creatinine (P < .01) and UP/UC (P < .01), but was not significantly associated
      with P-ClCr . CONCLUSIONS: Decreased levels of THP/UC were present in moderately
      to severely azotemic and proteinuric dogs. This suggests tubular injury in these
      dogs and that THP might be useful as urinary marker to study the pathogenesis of
      renal disease.

PMID- 24894071
TI  - Bis(methylpyridine)-EDTA derivative as a potential ligand for PET imaging:
      synthesis, complexation, and biological evaluation.
AB  - A novel transitional metal ligand derivatized from EDTA-conjugated 2-amino-4
      methyl pyridine, an acyclic vehicle (EDTA-Mepy2 ) was designed, synthesized, and
      characterized for PET imaging with 68Ga. The drug likeliness and appropriate
      lipophilicity were first analyzed by molecular docking studies which shows
      interactive property of ligand with serum albumin protein (HSA: PDB 1E78), at
      Lys199, Arg257, and His242 residues, which make it more appropriate in
      transportation as a specific ligand for PET imaging. As a confirmation, binding
      constant of the ligand with human serum albumin was calculated at lambdaex = 350
      nm which was found to be 4.9 * 103 m-1. The pharmacokinetics of (68) Ga-EDTA
      Mepy2 was analyzed by blood kinetics (t(1/2) slow: 3 h 56 min and t(1/2) fast: 32
      min) and biodistribution (maximum % ID/g was found in kidney at 1 h). Further the
      capability of this ligand was analyzed as optical marker also, by recording
      lambdaex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed lambdaem = 280
      nm. Additionally, in physiological conditions where its stability was calculated,
      suggests 15-20 times selectivity over the endogenously present metal ions (KG aL
      /KZ nL = 14.3, KG aL /KC uL = 18.1).

PMID- 24894072
TI  - High-pressure polymorphs of ZnCO3: evolutionary crystal structure prediction.
AB  - The high-pressure behavior of zinc carbonate ZnCO3 has been investigated using
      universal structure prediction method together with the density functional
      theory. In order to explore all possible structures under pressure, separate
      calculations at high pressure are done here with increasing number of formula
      units in the unit cell. Two pressures induced phase transitions were considered.
      The first one occurs at 78 GPa and the second one at 121 GPa. The most stable
      ZnCO3 at ambient condition corresponds to the space group R-3c (phase I), which
      is in favorable agreement with experiment. The structure with C2/m space group
      (phase II) becomes stable between 78 GPa and 121 GPa. Finally, the structure with
      the space group P2(1)2(1)2(1) (phase III) becomes the most stable when the
      pressure achieves 121 GPa. Some mechanical properties of R-3c structure were 
      additionally- calculated and compared with the experimental and previous
      theoretical data. The resulting behaviors support our findings and confirm the
      obtained phase transition. Besides, from the analysis of the electronic charge
      density it comes that at 78 GPa, new bond between oxygen and zinc is formed, what
      is likely the main cause behind the phase transition.

PMID- 24894073
TI  - Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling.
AB  - Receptor tyrosine kinases (RTKs) are a family of cell-surface receptors that have
      a key role in regulating critical cellular processes. Here, to understand and
      precisely control RTK signalling, we report the development of a genetically
      encoded, photoactivatable Trk (tropomyosin-related kinase) family of RTKs using a
      light-responsive module based on Arabidopsis thaliana cryptochrome 2. Blue-light
      stimulation (488 nm) of mammalian cells harbouring these receptors robustly
      upregulates canonical Trk signalling. A single light stimulus triggers transient
      signalling activation, which is reversibly tuned by repetitive delivery of blue
      light pulses. In addition, the light-provoked process is induced in a spatially
      restricted and cell-specific manner. A prolonged patterned illumination causes
      sustained activation of extracellular signal-regulated kinase and promotes
      neurite outgrowth in a neuronal cell line, and induces filopodia formation in rat
      hippocampal neurons. These light-controllable receptors are expected to create
      experimental opportunities to spatiotemporally manipulate many biological
      processes both in vitro and in vivo.

PMID- 24894074
TI  - Effects of Chk1 inhibition on the temporal duration of radiation-induced G2
      arrest in HeLa cells.
AB  - Chk1 inhibitor acts as a potent radiosensitizer in p53-deficient tumor cells by
      abrogating the G2/M checkpoint. However, the effects of Chk1 inhibitor on the
      duration of G2 arrest have not been precisely analyzed. To address this issue, we
      utilized a cell-cycle visualization system, fluorescent ubiquitination-based cell
      cycle indicator (Fucci), to analyze the change in the first green phase duration
      (FGPD) after irradiation. In the Fucci system, G1 and S/G2/M cells emit red and
      green fluorescence, respectively; therefore, G2 arrest is reflected by an
      elongated FGPD. The system also allowed us to differentially analyze cells that
      received irradiation in the red or green phase. Cells irradiated in the green
      phase exhibited a significantly elongated FGPD relative to cells irradiated in
      the red phase. In cells irradiated in either phase, Chk1 inhibitor reduced FGPD
      almost to control levels. The results of this study provide the first clear
      information regarding the effects of Chk1 inhibition on radiation-induced G2
      arrest, with special focus on the time dimension. 

PMID- 24894075
TI  - Some comments on 'Measurement of contractile forces generated by individual
      fibroblasts on self-standing fiber scaffolds' by Jeon et al. 2011.
AB  - In Jeon et al. (2011) reported on a series of novel experiments aimed at
      measuring contractile forces exerted by fibroblasts. In this short note, we
      provide some critical comments on their interpretation of scaffold deformation
      and their derivation of contractile force exerted by the fibroblasts. 

PMID- 24894076
TI  - Re: a comparative study of contrasting surgical residency programs.

PMID- 24894077
TI  - Gut-directed hypnotherapy in children with irritable bowel syndrome or functional
      abdominal pain (syndrome): a randomized controlled trial on self exercises at
      home using CD versus individual therapy by qualified therapists.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) and functional abdominal pain
      (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or
      recurrent abdominal pain. Treatment is challenging, especially in children with
      persisting symptoms. Gut-directed hypnotherapy (HT) performed by a therapist has
      been shown to be effective in these children, but is still unavailable to many
      children due to costs, a lack of qualified child-hypnotherapists and because it
      requires a significant investment of time by child and parent(s). Home-based
      hypnotherapy by means of exercises on CD has been shown effective as well, and
      has potential benefits, such as lower costs and less time investment. The aim of
      this randomized controlled trial (RCT) is to compare cost-effectiveness of
      individual HT performed by a qualified therapist with HT by means of CD recorded
      self-exercises at home in children with IBS or FAP(S). METHODS/DESIGN: 260
      children, aged 8-18 years with IBS or FAP(S) according to Rome III criteria are
      included in this currently conducted RCT with a follow-up period of one year.
      Children are randomized to either 6 sessions of individual HT given by a
      qualified therapist over a 3-month period or HT through self-exercises at home
      with CD for 3 months.The primary outcome is the proportion of patients in which
      treatment is successful at the end of treatment and after one year follow-up.
      Treatment success is defined as at least 50% reduction in both abdominal pain
      frequency and intensity scores. Secondary outcomes include adequate relief, cost
      effectiveness and effects of both therapies on depression and anxiety scores,
      somatization scores, QoL, pain beliefs and coping strategies. DISCUSSION: If the
      effectiveness of home-based HT with CD is comparable to, or only slightly lower,
      than HT by a therapist, this treatment may become an attractive form of therapy
      in children with IBS or FAP(S), because of its low costs and direct availability.
      TRIAL REGISTRATION: Dutch Trial Register number NTR2725 (date of registration: 1
      February 2011).

PMID- 24894079
TI  - A non-randomised, controlled clinical trial of an innovative device for negative
      pressure wound therapy of pressure ulcers in traumatic paraplegia patients.
AB  - The conventional methods of treatment of pressure ulcers (PUs) by serial
      debridement and daily dressings require prolonged hospitalisation, associated
      with considerable morbidity. There is, however, recent evidence to suggest that
      negative pressure wound therapy (NPWT) accelerates healing. The commercial
      devices for NPWT are costly, cumbersome, and electricity dependent. We compared
      PU wound healing in traumatic paraplegia patients by conventional dressing and by
      an innovative negative pressure device (NPD). In this prospective, non-randomised
      trial, 48 traumatic paraplegia patients with PUs of stages 3 and 4 were
      recruited. Patients were divided into two groups: group A (n = 24) received NPWT
      with our NPD, and group B (n = 24) received conventional methods of dressing. All
      patients were followed up for 9 weeks. At week 9, all patients on NPD showed a
      statistically significant improvement in PU healing in terms of slough clearance,
      granulation tissue formation, wound discharge and culture. A significant
      reduction in wound size and ulcer depth was observed in NPD as compared with
      conventional methods at all follow-up time points (P = 0.0001). NPWT by the
      innovative device heals PUs at a significantly higher rate than conventional
      treatment. The device is safe, easy to apply and cost-effective. 

PMID- 24894078
TI  - The effectiveness of computerized order entry at reducing preventable adverse
      drug events and medication errors in hospital settings: a systematic review and
      meta-analysis.
AB  - BACKGROUND: The Health Information Technology for Economic and Clinical Health
      (HITECH) Act subsidizes implementation by hospitals of electronic health records
      with computerized provider order entry (CPOE), which may reduce patient injuries
      caused by medication errors (preventable adverse drug events, pADEs). Effects on
      pADEs have not been rigorously quantified, and effects on medication errors have
      been variable. The objectives of this analysis were to assess the effectiveness
      of CPOE at reducing pADEs in hospital-related settings, and examine reasons for
      heterogeneous effects on medication errors. METHODS: Articles were identified
      using MEDLINE, Cochrane Library, Econlit, web-based databases, and bibliographies
      of previous systematic reviews (September 2013). Eligible studies compared CPOE
      with paper-order entry in acute care hospitals, and examined diverse pADEs or
      medication errors. Studies on children or with limited event-detection methods
      were excluded. Two investigators extracted data on events and factors potentially
      associated with effectiveness. We used random effects models to pool data.
      RESULTS: Sixteen studies addressing medication errors met pooling criteria; six
      also addressed pADEs. Thirteen studies used pre-post designs. Compared with paper
      order entry, CPOE was associated with half as many pADEs (pooled risk ratio (RR)
      = 0.47, 95% CI 0.31 to 0.71) and medication errors (RR = 0.46, 95% CI 0.35 to
      0.60). Regarding reasons for heterogeneous effects on medication errors, five
      intervention factors and two contextual factors were sufficiently reported to
      support subgroup analyses or meta-regression. Differences between commercial
      versus homegrown systems, presence and sophistication of clinical decision
      support, hospital-wide versus limited implementation, and US versus non-US
      studies were not significant, nor was timing of publication. Higher baseline
      rates of medication errors predicted greater reductions (P < 0.001). Other
      context and implementation variables were seldom reported. CONCLUSIONS: In
      hospital-related settings, implementing CPOE is associated with a greater than
      50% decline in pADEs, although the studies used weak designs. Decreases in
      medication errors are similar and robust to variations in important aspects of
      intervention design and context. This suggests that CPOE implementation, as
      subsidized under the HITECH Act, may benefit public health. More detailed
      reporting of the context and process of implementation could shed light on
      factors associated with greater effectiveness.

PMID- 24894080
TI  - Oviposition deterrent and ovicidal activities of seven herbal essential oils
      against female adults of housefly, Musca domestica L.
AB  - The oviposition deterrent and ovicidal of seven herbal essential oils derived
      from Citrus sinensis, Cymbopogon citratus, Eucalyptus glubulus, Illicium verum,
      Lavandula angustifolia, Mentha piperita, and Zingiber cussumunar were assessed
      against the gravid female of housefly, Musca domestica L., under laboratory
      conditions and compared with commercial insecticide (10% w/v cypermethrin). They
      were assayed at three concentrations (1.0, 5.0, and 10.0%) where plastic cups
      containing 1 ml of desired oil concentration and cotton pad soaked with 10 ml of
      milk solution (10% w/v) were used as oviposition substrate. The 0.1 ml of
      deferent concentrations was dropped on ten housefly eggs, which were used for
      ovicidal activity. The number of eggs laid and the hatched larvae in each cup was
      recorded to evaluate the oviposition deterrent and ovicidal activities of the
      herbal essential oils. High concentration (10%) of herbal essential oils showed
      high percent effective repellency (ER). The 10% I. verum oil caused complete
      oviposition deterrence (100% ER, oviposition activity index (OAI) = -1.0),
      followed by Z. cussumunar, M. piperita, L. angustifolia, C. citratus, C.
      sinensis, and E. glubulus oils with 97.20, 88.55, 88.14, 87.93, 76.68, and 57.00%
      ER, respectively. As the concentration of herbal essential oils increased from
      1.0, 5.0, and up to 10.0% concentration, the hatching rate decreased. Ten percent
      I. verum oil gave the maximum inhibiting rate at 97.3% (LC50 value of 6.85%); in
      addition, the other herbal essential oils showed the minimum inhibiting rate of
      3.3-22.7%. On the other hand, cypermethrin 10% w/v showed complete oviposition
      deterrence (100% ER, OAI = -1.0) and ovicidal activity (100% inhibiting rate).
      Our data showed that I. verum oil have high potential of oviposition deterrence
      and ovicide housefly control.

PMID- 24894081
TI  - Ultrastructural characteristics and molecular identification of Entamoeba suis
      isolated from pigs with hemorrhagic colitis: implications for pathogenicity.
AB  - Protozoan parasites of the genus Entamoeba infect many classes of vertebrates and
      are primarily classified based on morphological criteria. To date, only a few
      species have been proven to cause disease. Here, we examined the pathology of
      infected pigs with hemorrhage and detected Entamoeba parasites. Isolates were
      characterized genetically and ultrastructurally to identify the species.
      Histopathologically, bleeding and thrombus formation were seen only in the large
      intestine mucosa, where a large number of trophozoites or some Entamoeba cysts
      were observed around breakdowns in the lamina propria. No screw-shaped bacteria
      were detected in the lesions, and no pathogenic bacteria such as Brachyspira spp.
      were detected in fecal cultures. Interestingly, electron microscopy revealed that
      the parasites possessed mitochondrial organelles, unlike other Entamoeba spp. The
      isolates were identified as Entamoeba suis by PCR analysis and sequencing of the
      small subunit ribosomal RNA (SSU rRNA) gene. In phylogenetic analyses based on
      the actin gene, the E. suis isolate formed a cluster with Entamoeba histolytica
      and Entamoeba invadens, as well as with other parasites of the Amoebidae. Whether
      the pathogenicity of the E. suis isolate is affected by the severity of infection
      or host health status remains unclear; however, our results suggest that E. suis
      could cause or exacerbate clinical symptoms such as hemorrhagic colitis or
      diarrhea. 

PMID- 24894082
TI  - Present-day anthelmintics and perspectives on future new targets.
AB  - In absence of vaccines for the majority of helminths, chemotherapy is still the
      mainstay for controlling human helminthiases. However, a limited number of drugs
      are available in the market to combat parasitic helminths in human. Besides, the
      development and spread of drug resistance have declined the use of most currently
      available anthelmintics. Clearly, availability of new anthelmintic agents will be
      essential in the next few years. More research into the mechanisms of drug
      actions and their targets are eminent for the discovery and development of novel
      anthelmintic agents. Recent drug discovery techniques mostly rely on mechanism
      based screening of compounds on heterologously expressed targets in bacterial,
      mammalian or yeast cells. Although this is usually a successful approach, it is
      money- and time-consuming; meanwhile, pharmaceutical companies prefer the tested
      target that is chosen based on basic research. The nervous system is the site of
      action of several chemotherapeutics including pesticides and antinematode drugs;
      accordingly, the nervous system continues to be a promising target. Recent
      advances in exploring helminths' nervous system, neurotransmitters and receptors
      have paved the way for the development of potential agents targeting the nervous
      system and its components. 

PMID- 24894083
TI  - Proteomic identification of potential Clonorchis sinensis excretory/secretory
      products capable of binding and activating human hepatic stellate cells.
AB  - Epidemiological and experimental evidence demonstrated that Clonorchis sinensis
      is an important risk factor of hepatic fibrosis and cholangiocarcinoma. C.
      sinensis excretory/secretory products (CsESPs) are protein complex including
      proteases, antioxidant enzymes, and metabolic enzymes, which may contribute to
      pathogenesis of liver fluke-associated hepatobiliary diseases. However, potential
      CsESP candidates involved into hepatic fibrosis and cholangiocarcinoma still
      remain to be elucidated. In the present study, we performed proteomic
      identification of CsESP candidates capable of binding and activating human
      hepatic stellate cell line LX-2. Immunofluorescence analysis confirmed the
      interaction of CsESPs with LX-2 cell membrane. LX-2 cells could be stimulated by
      CsESPs from 24 h post incubation (p < 0.05). Specifically, 50 MUg/ml of CsESPs
      showed the strongest effect on cell proliferation in methyl thiazolyl tetrazolium
      (MTT) assay which could also be demonstrated by flow cytometry analysis (p <
      0.01). Furthermore, expression level of human type III collagen in LX-2 cells
      treated with CsESPs was significantly higher than that in control cells measured
      by molecular beacon and semiquantitative reverse transcription (RT)-PCR
      approaches (p < 0.01). Finally, CsESPs before and after incubation with LX-2
      cells were subjected to two-dimensional gel electrophoresis (2-DE) analysis and
      matrix associated laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry analysis. Nine proteins with abundance change above threefold were
      Rho GTPase-activating protein, mitochondrial cytochrome c oxidase subunit Va,
      alpha-enolase, phospholipase C, interleukin-15, insect-derived growth factor,
      cytochrome c oxidase subunit VI, DNAH1 protein, and kinesin light chain. Taken
      together, we identified potential CsESP candidates capable of binding and
      activating human hepatic stellate cells, providing more direct evidences that are
      previously unknown to accelerate strategies for C. sinensis prevention.

PMID- 24894084
TI  - A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem
      cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin
      based chemotherapy: the Multicentric TAXIF II study.
AB  - BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of
      germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of
      patients may achieve durable remissions. Even when HDCT is administered as
      subsequent salvage treatment, up to 20% of patients may still be definitively
      cured. However, patients with refractory/relapsed disease still have a very poor
      long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND
      METHODS: This phase II trial was addressed to nonrefractory patients failing
      Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in
      relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after
      first or second lines, partial remission after first line, primary mediastinal
      GCT in first relapse. Patients received two cycles combining Epirubicin and
      Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a
      Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide
      Carboplatin-Etoposide regimen. The main objective was to determine the complete
      response rate. RESULTS: Forty-five patients were included between September 2004
      and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could
      receive the whole protocol. Sixteen patients did not receive the entire protocol,
      including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of
      toxicities, and 17 (37.7%) of disease progression. With a median follow-up time
      of 26 months (range, 4-51), the final overall response rate was 48.8% (including
      a complete response rate of 15.5% and a partial response/negative serum markers
      rate of 26.6%) in an intent-to-treat analysis. The median progression-free
      survival (PFS) and overall survival (OS) times were 22 months [95% confidence
      interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2
      year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95%
      CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT
      patients failing Cisplatin-based chemotherapy. The toxic death rate remained
      acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.

PMID- 24894085
TI  - Expression and cellular distribution of TLR4, MyD88, and NF-kappaB in diabetic
      renal tubulointerstitial fibrosis, in vitro and in vivo.
AB  - AIM: Inflammation and extracellular matrix hyperplasia are crucial in the
      pathogenesis of tubulointerstitial fibrosis (TIF) involved in diabetic
      nephropathy (DN). Macrophage accumulation plays a major role, but whether immune
      factors contribute to DN pathogenesis is not well understood. This study aimed to
      investigate TLR4-MyD88-NF-kappaB-dependent pathway's involvement in TIF
      pathogenesis. METHODS: STZ-induced diabetic rats and rat renal tubular epithelial
      NRK-52E cells cultured under high glucose conditions were used as in vivo and in
      vitro models, respectively. Real-time RT-PCR, western blot, immunohistochemistry
      and immunofluorescence were performed to examine the mRNA and protein levels of
      TLR4, MyD88, NF-kappaB, MCP-1, and alpha-SMA. RESULTS: Compared with 5.5 mmol/L
      glucose, treatment of NRK-52E cells with 25 and 50 mmol/L d-glucose resulted in
      significantly increased TLR4 and MyD88 mRNA and protein levels (P<0.05). TLR4 and
      MyD88 were detected in the cytoplasm of most NRK-52E cells cultured under high
      glucose. Pronounced damage in the renal tubulointerstitium was observed in
      diabetic rats (scores: 3.82 +/- 0.65 vs. 0.38 +/- 0.08, P<0.01). Compared with
      the normal controls, a sharp upregulation of TLR4, MyD88, NF-kappaB p65, MCP-1,
      and alpha-SMA mRNA and protein levels was observed in diabetic rat kidneys
      (P<0.05). In diabetic animals, TLR4 and MyD88 were strongly expressed in the
      cytoplasm, while NF-kappaB p65 was widely expressed in cytoplasm and nuclei of
      renal tubular epithelial cells. CONCLUSION: The inflammatory reaction and
      epithelial-mesenchymal transformation observed in renal tubulointerstitium may be
      the result of overactivation of the TLR4-MyD88-NF-kappaB-dependent innate
      immunity under high glucose, and may be involved in DN occurrence and
      progression.

PMID- 24894086
TI  - Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of
      nephropathy in Taiwanese male patients with type 2 diabetes.
AB  - AIMS: Polymorphisms of the ADIPOQ gene were associated with diabetic nephropathy
      (DN) in case-control studies predominantly among European populations. Gender may
      modify the ADIPOQ associated risk for DN. We investigated the association of 18
      ADIPOQ polymorphisms with DN in a prospective Taiwanese cohort of type 2 diabetes
      (T2D) and explored whether gender plays a role in this genetic association.
      METHODS: Selected single nucleotide polymorphisms (SNPs) of ADIPOQ were genotyped
      in 566 T2D patients with normoalbuminuria at baseline. DN was defined based on
      urinary albumin-to-creatinine ratio (ACR). The Cox proportional hazard model was
      used to explore the association of individual SNP to DN events under different
      genetic models over a 6-year follow-up period. Analyses were further stratified
      by gender. RESULTS: In male patients, the adjusted hazard ratios under the
      recessive models were 1.81 for rs2241766 TT (vs. GT+GG, 95% CI=1.10-2.96,
      p=0.019) and 1.89 for rs1063537 CC (vs. CT+TT, 95% CI=1.15-3.11, p=0.013). In the
      Kaplan-Meier survival curve, males carrying rs2241766 TT (vs. GT+GG, p=0.050) and
      rs1063537 CC (vs. CT+TT, p=0.037) recessive homozygotes also had a reduced
      nephropathy-free survival rate. SNPs rs2241767 and rs2082940, both in strong
      correlation with tag SNP rs1063537 (r(2)>= 0.96), were also associated with DN
      progression in males. In females, ADIPOQ polymorphisms were not associated with
      the progression of DN. CONCLUSIONS: ADIPOQ genetic polymorphisms rs2241766
      (+45T>G), rs1063537, rs2241767 and rs2082940 were correlated with the progression
      of DN in Taiwanese male patients with T2D. The role of gender in this ADIPOQ
      genetic association needs to be further investigated in other populations.

PMID- 24894087
TI  - Pathogen-sensing and regulatory T cells: integrated regulators of immune
      responses.
AB  - We present the concept that pathogen-sensing and regulatory T cells (Treg)
      mutually regulate immune responses to conventional and tumor antigens through
      countervailing effects on dendritic cells (DC). Normally, conventional CD4 T
      cells recognizing their cognate antigen presented by a DC will respond only if
      the DC also receives a signal through its pathogen-sensing/danger/adjuvant
      recognition systems (the pathogen-sensing triad). However, in the absence of
      Tregs capable of interacting with the same DC, DCs are competent to present
      antigens, both foreign and self, even without the stimulation provided by the
      pathogen-sensing triad. Tregs recognizing an antigen presented by the DC that is
      also presenting antigen to a conventional CD4 T cell will prevent the activation
      of the CD4 T-cell responses, but a signal delivered by a member of the pathogen
      sensing triad will overcome the inhibitory action of Tregs, thus allowing CD4 T
      cell responses to go forward. These considerations take on special meaning for
      responses to "weak antigens" such as many of the antigens displayed by
      spontaneous human tumors.

PMID- 24894088
TI  - VISTA is a novel broad-spectrum negative checkpoint regulator for cancer
      immunotherapy.
AB  - In the past few years, the field of cancer immunotherapy has made great progress
      and is finally starting to change the way cancer is treated. We are now learning
      that multiple negative checkpoint regulators (NCR) restrict the ability of T-cell
      responses to effectively attack tumors. Releasing these brakes through antibody
      blockade, first with anti-CTLA4 and now followed by anti-PD1 and anti-PDL1, has
      emerged as an exciting strategy for cancer treatment. More recently, a new NCR
      has surfaced called V-domain immunoglobulin (Ig)-containing suppressor of T-cell
      activation (VISTA). This NCR is predominantly expressed on hematopoietic cells,
      and in multiple murine cancer models is found at particularly high levels on
      myeloid cells that infiltrated the tumors. Preclinical studies with VISTA
      blockade have shown promising improvement in antitumor T-cell responses, leading
      to impeded tumor growth and improved survival. Clinical trials support combined
      anti-PD1 and anti-CTLA4 as safe and effective against late-stage melanoma. In the
      future, treatment may involve combination therapy to target the multiple cell
      types and stages at which NCRs, including VISTA, act during adaptive immune
      responses.

PMID- 24894089
TI  - HLA-binding properties of tumor neoepitopes in humans.
AB  - Cancer genome sequencing has enabled the rapid identification of the complete
      repertoire of coding sequence mutations within a patient's tumor and facilitated
      their use as personalized immunogens. Although a variety of techniques are
      available to assist in the selection of mutation-defined epitopes to be included
      within the tumor vaccine, the ability of the peptide to bind to patient MHC is a
      key gateway to peptide presentation. With advances in the accuracy of predictive
      algorithms for MHC class I binding, choosing epitopes on the basis of predicted
      affinity provides a rapid and unbiased approach to epitope prioritization. We
      show herein the retrospective application of a prediction algorithm to a large
      set of bona fide T cell-defined mutated human tumor antigens that induced immune
      responses, most of which were associated with tumor regression or long-term
      disease stability. The results support the application of this approach for
      epitope selection and reveal informative features of these naturally occurring
      epitopes to aid in epitope prioritization for use in tumor vaccines.

PMID- 24894090
TI  - Tumor MHC class I expression improves the prognostic value of T-cell density in
      resected colorectal liver metastases.
AB  - Tumor-infiltrating lymphocytes (TIL) in colorectal cancer liver metastases (CLM)
      have been associated with more favorable patient outcomes, but whether MHC class
      I (MHC-I) expression on cancer cells affects prognosis is uncertain.
      Immunohistochemistry was performed on a tissue microarray of 158 patients with
      CLM, who underwent partial hepatectomy with curative intent. Using the antibody
      HC-10, which detects HLA-B and HLA-C antigens and a minority of HLA-A antigens,
      MHC-I expression was correlated with beta-2 microglobulin (beta2m; r = 0.7; P <
      0.001), but not with T-cell density (r < 0.32). The median follow-up for
      survivors was 9.7 years. High levels of MHC-I expression in tumors concomitant
      with high T-cell infiltration (CD3, CD4, or CD8) best identified patients with
      favorable outcomes, compared with patients with one or none of these immune
      features. The median overall survival (OS) of patients with MHC-I(hi)CD3(hi)
      tumors (n = 31) was 116 months compared with 40 months for the others (P =
      0.001), and the median time to recurrence (TTR) was not reached compared with 17
      months (P = 0.008). By multivariate analysis, MHC(hi)CD3(hi) was associated with
      OS and TTR independent of the standard clinicopathologic variables. An immune
      score that combines MHC-I expression and TIL density may be a valuable prognostic
      tool in the treatment of patients with CLM.

PMID- 24894091
TI  - Immune-escape markers in relation to clinical outcome of advanced melanoma
      patients following immunotherapy.
AB  - In this study, we investigated a large series of immune (escape) markers,
      relevant to T-cell function, as potential biomarkers for clinical outcome
      following immunotherapy. We retrospectively studied the expression of immune
      (escape) markers in metastatic melanoma tissues of 27 patients before autologous
      tumor cell vaccination, and 16 patients who were intended to treat but were not
      vaccinated because of rapid disease progression. Immunohistochemical data of
      infiltrating (suppressive) cells, such as T cells, regulatory T cells, myeloid
      derived suppressor cells, and mast cells, or the expression of T-cell inhibitory
      factors (PD-1/PD-L1, IDO, and galectins), cytotoxic molecules (granzyme-B),
      melanocyte differentiation antigens, HLA class-I and tolerogenic cytokines
      [interleukin (IL)-1, IL-6, IL-10, TNF-alpha, and TGF-beta] were correlated
      statistically to clinical outcome and overall survival (OS). Significantly more
      tumor-infiltrating CD4(+) and CD8(+) T cells (both P < 0.05) were found in
      nonprogressors to vaccination (n = 9; median OS, 56 months), compared with
      progressors (n = 18; median OS, 9.5 months). Moreover, granzyme-B expression was
      elevated in the tumors of nonprogressors, suggesting activated cytotoxic T cells
      or natural killer cells. T-cell infiltration and granzyme-B expression
      significantly correlated with overall OS. T-cell inhibitory factors and
      suppressive cells did not correlate with OS, suggesting minor influence of these
      immune-escape markers on clinical outcome. The data of progressors were
      comparable with those from patients with rapid progression (not vaccinated; n =
      16; median OS, 3 months). Our study shows that high numbers of intratumoral
      activated CD4(+) or CD8(+) T cells, before autologous tumor cell vaccination, are
      associated with favorable clinical outcome. Analyses of these markers in the
      patients' tumor tissues before immunotherapy may therefore be a valuable tool to
      select patients for whom the treatment may result in potential clinical benefit.

PMID- 24894092
TI  - Cancer-testis antigen 7 expression and immune responses following allogeneic stem
      cell transplantation for multiple myeloma.
AB  - Cancer-testis antigen 7 (CT7) is the most frequently and consistently expressed
      MAGE antigen in multiple myeloma, exhibits tissue-restricted expression, and is
      an independent negative prognostic factor for multiple myeloma. We sought to
      characterize CT7 protein expression in the bone marrow of patients with multiple
      myeloma undergoing allogeneic T cell-depleted hematopoietic stem cell
      transplantation (alloTCD-HSCT), and to examine the significance of CT7-specific
      cellular immune responses. We further aimed to determine CT7-derived immunogenic
      epitopes and their associated allelic restrictions. CT7 protein expression in
      neoplastic CD138(+) plasma cells was evaluated by immunohistochemistry in bone
      marrow biopsies from 10 patients. CT7 was present in 8 of 10 patients.
      Longitudinal analyses of the 10 patients revealed an association between CT7
      expression and prognosis. Longitudinal monitoring of CT7-specific T cells
      revealed an association between increased frequencies of CT7-specific T cells and
      reductions in specific myeloma markers. Epitope-specific reactivity to the
      nonamer FLAMLKNTV was detected by intracellular IFNgamma assay in peripheral
      blood (PB) and bone marrow-derived T cells from HLA-A*0201(+) patients. Serial
      monitoring of PB CT7-specific T-cell frequencies in 4 HLA-A*0201(+) patients by
      HLA-A*0201-CT7(1087-1095) tetramer staining revealed an association with disease
      course. Phenotypic analyses revealed bone marrow enrichment for central memory
      CT7-specific T cells, while effector memory cells dominated the PB. Together,
      these findings support the development of immunotherapeutic strategies that aim
      to enhance CT7-directed immune responses for the treatment of multiple myeloma.

PMID- 24894094
TI  - Thoracic endovascular stent graft infection.

PMID- 24894093
TI  - Antitumor effects of cisplatin combined with tecemotide immunotherapy in a human
      MUC1 transgenic lung cancer mouse model.
AB  - The goals of the present study were to define the effects of simultaneous
      cisplatin/tecemotide therapy on tumor development in a human mucin 1 (MUC1)
      transgenic lung cancer mouse model and to examine the effects of radiotherapy
      (RTX) on splenocytes, serum cytokines, and immune response to tecemotide. Two
      hundred twenty-six human MUC1 transgenic C57BL/6 mice were used in five studies
      designed to assess (i) serum cytokine and immune responses following four weekly
      10-MUg doses of tecemotide; (ii) the effects of simultaneous administration of
      cisplatin (2.5 mg/kg * 2 doses/cycle * 4 cycles) and tecemotide (2 cycles * 8
      weekly 10-MUg doses/cycle) therapy on tumor development, serum cytokines, and
      immune response; (iii) the dose-response effects of RTX on lymphocyte counts 16
      hours following doses of 2 to 8 Gy; (iv) the time course of lymphocyte recovery
      from 16 hours to 20 days following 8-Gy RTX; and (v) the effects of simultaneous
      administration of RTX (8 Gy) and tecemotide on the immune response to tecemotide
      (four weekly 10-MUg doses). Serum cytokines were analyzed by multiplex
      immunoassay, IFNgamma immune responses by enzyme-linked immunosorbent spot
      (ELISpot), and lung tumor foci by lung whole mounts. Simultaneous
      cisplatin/tecemotide therapy resulted in significant and additive reduction in
      lung tumor foci compared with control mice, with significantly elevated serum
      IFNgamma levels and specific IFNgamma immune responses observed in both
      tecemotide and tecemotide + cisplatin-treated mice. Finally, neither cisplatin
      nor radiation interfered with the immune response to tecemotide.

PMID- 24894095
TI  - Impact of the epidermal growth factor receptor mutation status on the post
      recurrence survival of patients with surgically resected non-small-cell lung
      cancer.
AB  - OBJECTIVES: The impact of epidermal growth factor receptor (EGFR) status and the
      use of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy have not been well
      discussed only in recurrent non-small-cell lung cancer (NSCLC). The purpose of
      this study was to identify the prognostic factors associated with post-recurrence
      survival after surgical resection of NSCLC in terms of the EGFR mutation status
      and the use of EGFR-TKI therapy. METHODS: From 2000 through 2011, 1237
      consecutive patients with NSCLC underwent pulmonary resection at our institution.
      Of these patients, 280 experienced postoperative recurrence by the end of 2012.
      We reviewed the cases of recurrence and analysed the predictors and length of
      post-recurrence survival. RESULTS: The median post-recurrence survival time and
      the 5-year survival rate of all patients were 25 months and 20.8%, respectively.
      A multivariate analysis identified the Eastern Cooperative Oncology Group (ECOG)
      performance status (PS), brain metastasis, number of sites of recurrence and EGFR
      mutation status to be independent prognostic factors for post-recurrence
      survival. Among all cases, the median post-recurrence survival time according to
      the use of EGFR-TKI therapy was as follows: 49 months in the EGFR mutation
      positive patients treated with EGFR-TKI therapy, 20 months in the EGFR wild or
      unknown cases treated with EGFR-TKI therapy and 17 months in the patients not
      treated with EGFR-TKI therapy. As to EGFR mutation-positive cases, the patients
      treated with EGFR-TKIs exhibited significantly longer post-recurrence survival
      time than the patients treated without EGFR-TKIs (49 vs 12 months). CONCLUSIONS:
      It is essential for recurrent NSCLC patients to be examined for the EGFR mutation
      status. Patients with a positive EGFR mutation status receive significant
      benefits from EGFR-TKI therapy.

PMID- 24894096
TI  - Skin cancer as a marker of sun exposure: a case of serious immortality bias.

PMID- 24894097
TI  - Authors' Response to: Skin cancer as a marker of sun exposure--a case of serious
      immortality bias.

PMID- 24894098
TI  - Psychiatric epidemiology, or the story of a divided discipline.
AB  - This article traces the historical decisions, concepts and key professional
      collaborations that laid the foundations for the formation of American
      psychiatric epidemiology during the 20th century, up to the discipline's
      institutional consolidation, circa 1980, when the third edition of the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-III) was published. Thomas Kuhn's
      'disciplinary matrix' is mobilized as a framework that allows the institutional
      and intellectual construction of a discipline to be analysed as separate but
      intertwined components, without assuming that the two evolve in tandem. The
      identification of the strengths as well as the frailties and internal divisions
      of the discipline as it developed reveals a paradoxical situation: a time lag
      between psychiatric epidemiology's institutionalization and public recognition,
      on the one hand; and the weak coherence of its intellectual components, on the
      other hand. We briefly trace the origins of split among the discipline's
      aetiological models of mental disorders and suggest that the lack of coherence
      among them has prevented psychiatric epidemiology from achieving the status of a
      normal scientific discipline, in the Kuhnian sense. Without a more explicit
      attention to the intellectual rationale of the discipline, psychiatric
      epidemiology will continue to maintain a strong institutional dimension and weak
      intellectual matrix. 

PMID- 24894099
TI  - Living with faecal incontinence: trying to control the daily life that is out of
      control.
AB  - AIMS AND OBJECTIVES: To identify and describe the lived experience of persons
      living with faecal incontinence and show how it affects daily life. BACKGROUND:
      Faecal incontinence is a relatively common condition, with a prevalence ranging
      from 3-24%, not differing between men and women. There is an under-reporting due
      to patients' reluctance to talk about their symptoms and consult healthcare
      professionals about their problems, which means that problems related to faecal
      incontinence are often underestimated. Living with faecal incontinence affects
      the quality of life negatively and has a negative impact on family situations,
      social interaction, etc. DESIGN: A qualitative interpretative study based on
      interviews. METHODS: In-depth interviews were conducted with five informants, all
      women, living with faecal incontinence. The interviews were transcribed verbatim
      and analysed using interpretive phenomenological analysis. RESULTS: The analysis
      identified four themes: self-affirmation, guilt and shame, limitations in life
      and personal approach. The themes differ from each other, but are related and
      have similarities. The results show different aspects of living with faecal
      incontinence and how they affected daily life. CONCLUSIONS: Living with faecal
      incontinence is a complex problem affecting everyday life in a number of
      different ways. It is a highly distressing and socially incapacitating problem.
      Living with faecal incontinence is about trying to control the daily life which
      is out of control. Living with faecal incontinence cannot be generalised as
      individuals experience the situation in unique ways. RELEVANCE TO CLINICAL
      PRACTICE: By gaining insight into the experience of living with faecal
      incontinence, healthcare professionals can deepen their understanding of this
      complex problem and thereby better address it and provide more individually based
      care.

PMID- 24894100
TI  - Assessing phagocytic clearance of cell death in experimental stroke by ligatable
      fluorescent probes.
AB  - We describe a new histochemical approach for visualization of phagocytic
      clearance in focal brain ischemia. The approach permits the study of elimination
      of dead cells in stroke by waste-management phagocytes of any cellular lineage.
      Although numerous cells of different origins that are capable of phagocytosis are
      present in ischemic brain, only part of them actively engulf and digest cell
      corpses. The selective visualization, quantification and analysis of such active
      phagocytic waste-management are helpful in assessing brain response to ischemia.
      Efficient cell death clearance is important for brain recovery from ischemic
      injury, as it opens the way for the subsequent regenerative processes. The
      failure to clean the corpses would result in a toxic reaction caused by non
      degraded DNA and proteins. The described procedure uses fluorescent probes
      selectively ligated by a viral topoisomerase to characteristic DNA breaks
      produced in all phagocytes during engulfment and digestion of cells irreversibly
      damaged by ischemia. The method is a new tool for the investigation of brain
      reaction to ischemic injury. 

PMID- 24894102
TI  - Negative electrodes for Na-ion batteries.
AB  - Research interest in Na-ion batteries has increased rapidly because of the
      environmental friendliness of sodium compared to lithium. Throughout this
      Perspective paper, we report and review recent scientific advances in the field
      of negative electrode materials used for Na-ion batteries. This paper sheds light
      on negative electrode materials for Na-ion batteries: carbonaceous materials,
      oxides/phosphates (as sodium insertion materials), sodium alloy/compounds and so
      on. These electrode materials have different reaction mechanisms for
      electrochemical sodiation/desodiation processes. Moreover, not only sodiation
      active materials but also binders, current collectors, electrolytes and
      electrode/electrolyte interphase and its stabilization are essential for long
      cycle life Na-ion batteries. This paper also addresses the prospect of Na-ion
      batteries as low-cost and long-life batteries with relatively high-energy density
      as their potential competitive edge over the commercialized Li-ion batteries. 

PMID- 24894101
TI  - A Monte Carlo study of the energy spectra and transmission characteristics of
      scattered radiation from x-ray computed tomography.
AB  - Existing data used to calculate the barrier transmission of scattered radiation
      from computed tomography (CT) are based on primary beam CT energy spectra. This
      study uses the EGSnrc Monte Carlo system and Epp user code to determine the
      energy spectra of CT scatter from four different primary CT beams passing through
      an ICRP 110 male reference phantom. Each scatter spectrum was used as a broad
      beam x-ray source in transmission simulations through seventeen thicknesses of
      lead (0.00-3.50 mm). A fit of transmission data to lead thickness was performed
      to obtain alpha, beta and gamma parameters for each spectrum. The mean energy of
      the scatter spectra were up to 12.3 keV lower than that of the primary spectrum.
      For 120 kVp scatter beams the transmission through lead was at least 50% less
      than predicted by existing data for thicknesses of 1.5 mm and greater; at least
      30% less transmission was seen for 140 kVp scatter beams. This work has shown
      that the mean energy and half-value layer of CT scatter spectra are lower than
      those of the corresponding primary beam. The transmission of CT scatter radiation
      through lead is lower than that calculated with currently available data. Using
      the data from this work will result in less lead shielding being required for CT
      scanner installations. 

PMID- 24894104
TI  - Health-related quality of life and well-being in adults with idiopathic
      inflammatory myopathy.
AB  - Health-related quality of life (HRQoL) and well-being are concepts that attempt
      to objectively capture a person's subjective perceptions of vitality and energy.
      Our objectives were to determine HRQoL and well-being in adult patients diagnosed
      with inflammatory myopathy who attended at our outpatient clinic and to
      investigate clinical and biological correlations with these concepts. Sixty-two
      patients (52 women), with a mean age of 50.7 years, were evaluated in this cross
      sectional study-47 with dermatomyositis and 15 with polymyositis. Disease damage
      and activity were assessed with the International Myositis Assessment and
      Clinical Studies-validated instruments. Manual muscle testing was used to
      evaluate muscle strength. Quality of life was evaluated with the WHO instrument
      (WHO Quality of Life Measure (WHOQOL-BREF)), adapted for use in the Spanish
      population, and well-being with the WHO-Five Well-Being Index (WHO-5). t tests
      were conducted to examine differences in HRQoL and well-being outcomes in
      relation to several disease- and patient-related variables. Correlation analyses
      were performed with the Pearson correlation coefficient. None of the clinical or
      biological variables analyzed was significantly associated with a poorer HRQoL or
      well-being. No differences in HRQoL or WHO-5 well-being score were found between
      the two myositis subgroups (dermatomyositis vs. polymyositis). Disease activity
      and muscle weakness were negatively associated with the physical and
      environmental domains of the HRQoL, respectively (p < 0.002), but not with well
      being. Disease duration did not have a significant impact on HRQoL or well-being.
      In adult patients with myositis, disease activity and muscle weakness are
      associated with poorer HRQoL in the physical health and environmental domains,
      respectively. 

PMID- 24894105
TI  - Fertility, ovarian failure, and pregnancy outcome in SLE patients treated with
      intravenous cyclophosphamide in Saudi Arabia.
AB  - Intravenous cyclophosphamide (IV CYC) has been and still used for treatment of
      severe manifestations of systemic lupus erythematosus (SLE), a disease occurring
      predominantly in women. IV CYC has been shown to predispose patients to ovarian
      failure and adverse pregnancy outcomes. We studied the impact of prior IV CYC
      treatment on ovarian function and pregnancy in our SLE patients, in terms of
      amenorrhea, fertility, and pregnancy outcome over a 26-year period. The study
      included 535 women (319 married), out of which 188 received IV CYC and 347 did
      not. Sixty-one patients experienced amenorrhea; the rate of amenorrhea in IV CYC
      user group (28.2 %; n = 53) was significantly higher than that in non-IV CYC
      group (3.7 %; n = 8) (P < 0.05). The type of amenorrhea was assessed in 99 women
      receiving IV CYC. Thirty-four (34.3 %) of them developed amenorrhea which was
      transient in 21 (21.2 %) and sustained in 13 (13.1 %) women. The older age at the
      time of receiving IV CYC and its higher cumulative dose were found to be risk
      factors for amenorrhea. Among married women, 48 of 99 (48.5 %) in IV CYC group
      conceived 90 pregnancies and 128 of 220 (58.2 %) in non-IV CYC group conceived
      293 pregnancies. The rates of abortions, fetal loss, and live births between the
      two groups were similar; however, women with prior IV CYC had significantly more
      preterm births. Prior IV CYC was no barrier to conception; pregnancy outcome was
      favorable but associated with amenorrhea and preterm deliveries.

PMID- 24894106
TI  - Rheumatoid arthritis in the developing world: stepping up to the challenge.

PMID- 24894103
TI  - Serum C-reactive protein level but not its gene polymorphism is associated with
      Takayasu arteritis.
AB  - Takayasu arteritis (TA) patients with active disease often have elevated serum C
      reactive protein (CRP) levels, which usually decline with the disease remission.
      The serum CRP concentration has been showed to be related to CRP gene
      polymorphisms in previous studies. The present study aims to investigate the
      associations of serum level of CRP and CRP polymorphisms with TA. A total of 178
      unrelated Chinese Han TA patients and 229 unrelated Chinese Han individuals
      without documented disease were enrolled in our studies. After a systemic search
      in the HapMap database, four single-nucleotide polymorphisms (SNPs) were
      selected, namely, rs1800947, rs3093077, rs1205, and rs2808630. The ligase
      detection reaction (LDR) was used in genotyping. CRP concentrations were
      determined using turbidimetric immunoassay. Genotype frequencies and allele
      frequencies of CRP variations were similar between TA patients and controls. CRP
      haplotype frequencies in patients were not significantly different from those of
      controls. No significant association between serum CRP concentrations and
      genotypes was found. Moreover, no association was found in CRP concentration
      between patients with types I, II, and III TA or between patients with or without
      pulmonary involvement. By contrast, serum CRP concentration was directly
      correlated with disease severity. In conclusion, CRP polymorphisms were not
      associated with TA susceptibility or serum CRP levels in the Chinese Han
      population. However, higher CRP level was correlated with a more serious disease
      status, which implies that CRP possibly contributes to the progression of TA.

PMID- 24894107
TI  - Dystrophic calcinosis with both a huge calcified mass in the cervical spine and
      calcification in the chest wall in a patient with rheumatoid overlap syndrome.
AB  - Dystrophic calcinosis in soft tissue occurs in damaged or devitalized tissues in
      the presence of normal calcium and phosphorous metabolism. It is often noted in
      subcutaneous tissues in patients with collagen vascular diseases and may involve
      a relatively localized area or be widespread. A 74-year-old Japanese woman with
      an overlap of rheumatoid arthritis, Sjogren's syndrome, and systemic sclerosis
      developed a huge tumor-like mass at the atlanto-axial vertebral joint region that
      caused severe cervical pain and difficulty in activities of daily living. She
      also had subcutaneous dystrophic calcification in the soft tissue of the chest
      wall. Calcinosis associated with systemic sclerosis is a well-recognized
      phenomenon, but a destructive paraspinal tumor in the cervical spine associated
      with overlap syndrome is extremely unique. Because calcinosis in spinal locations
      can be complicated by neurological involvement, patients with progressive
      symptoms may require surgical intervention. Surgical resection and biological
      therapy improved this patient's life and activities of daily living. Calcinosis
      is common in the conditions reviewed here, and different agents have been used
      for treatment. However, calcinosis management is poorly organized and lacks an
      accepted classification, systematic studies, and clinical therapeutic trials. The
      association of calcinosis and collagen vascular diseases is clinically and
      etiologically important. Although a combination of calcinosis and rheumatoid
      overlap syndrome is rare, various collagen vascular diseases may occur
      simultaneously. A perceptive diagnostic approach toward these diseases is
      critical, and early diagnosis and treatment are needed to prevent dystrophic
      calcinosis. 

PMID- 24894109
TI  - Ameboma: an unusual cause of gastrointestinal bleeding during severe
      leptospirosis.
AB  - BACKGROUND: Severe leptospirosis occurs mainly in a tropical environment and
      includes icterus, acute renal failure and hemorrhages. These bleedings, which are
      mainly a consequence of acute homeostatic disturbances, can also reveal
      simultaneous diseases. Coinfections with other tropical diseases have been
      previously reported during leptospirosis. To our knowledge, invasive amebiasis,
      which can induce gastrointestinal bleedings, has never been described in the
      course of severe leptospirosis. CASE PRESENTATION: In this report, we describe a
      case of a 60 year-old man living in Reunion Island (Indian Ocean, France)
      admitted to our intensive care unit for severe Leptospira interrogans serovar
      icterohaemorrhagiae infection with neurological, renal, liver and hematological
      involvement. Two lower gastrointestinal bleedings occurred 7 and 15 days after
      admission. The first episode was promoted by hemostatic disturbances while the
      second bleeding occurred during low-dose heparin therapy. Colonoscopy revealed a
      pseudo-tumoral inflammatory mass of the recto-sigmoid junction. Histological
      examination found trophozoites inside mucinous exudate suggestive of Entamoeba
      histolytica. Amoebic serology was strongly positive whereas careful detection of
      cysts or trophozoites on saline-wet mount was negative in three consecutive
      samples of stools. Amoxicillin followed by metronidazole therapy, combined with
      supportive care, led to an improvement in the clinical and biological patient's
      condition and endoscopic appearances. CONCLUSION: Clinicians should be aware that
      gastrointestinal bleeding during severe leptospirosis could not solely be the
      consequences of hemostatic disturbances. Careful endoscopic evaluation that may
      reveal curable coinfections should also be considered.

PMID- 24894110
TI  - The pregnant therapist: the effect of a negative pregnancy outcome on a
      psychotherapy patient.
AB  - In psychiatry, pregnancy introduces an element into the treatment setting that is
      complex and may require exploration. Often, in the psychotherapeutic
      relationship, the psychiatrist may use therapeutic techniques and provide no self
      disclosure to the patient by Tinsley (Am J Psychiatry 160(1): 27-31, 2003). The
      patient reveals all of their innermost thoughts. This can bring about curiosity
      for the patient about the clinician's life and result in asking personal
      questions which can at times be uncomfortable for the therapist, particularly for
      those still in training. This may feel like a boundary crossing which can pose a
      therapeutic challenge. The clinician is challenged to further enhance the
      therapeutic relationship and further help the patient on their journey to self
      exploration. While it is inevitable that patients will have reactions to their
      therapists, this can be played out in a number of ways, both at the conscious and
      unconscious level. While numerous studies have looked at the impact of the
      therapist's pregnancy on the patient and their treatment, there is no information
      about the effect of a therapist having a negative pregnancy outcome. Negative
      outcomes include the therapist having a miscarriage, delivering a still-born or
      both the therapist and baby dying. This case report describes a clinical scenario
      in which a psychiatry resident in training delivered a stillborn baby at 37 weeks
      and the impact of that on a long term psychotherapy patient.

PMID- 24894108
TI  - Acute rheumatic fever and streptococci: the quintessential pathogenic trigger of
      autoimmunity.
AB  - Acute rheumatic fever (ARF) is a non-suppurative complication of pharyngeal
      infection with group A streptococcus. Signs and symptoms of ARF develop 2 to 3
      weeks following pharyngitis and include arthritis, carditis, chorea, subcutaneous
      nodules, and erythema marginatum. In developing areas of the world, ARF and
      rheumatic heart disease are estimated to affect nearly 20 million people and
      remain leading causes of cardiovascular death during the first five decades of
      life. ARF still represents one of the quintessential examples of a pathogenic
      trigger culminating in autoimmune manifestations. In this review, we will focus
      on the pathogenesis and etiology of ARF and its complications, along with
      diagnostic and treatment approaches to both ameliorate and prevent long-term
      sequelae of this potentially debilitating disease. 

PMID- 24894111
TI  - Elucidation of phosphatidylcholine isomers using two dimensional liquid
      chromatography coupled in-line with ozonolysis mass spectrometry.
AB  - In this study, two dimensional (2D) liquid chromatography (LC) was coupled in
      line with ozonolysis-mass spectrometry (O3-MS) for the elucidation of
      phosphatidylcholine (PC) structures in phospholipid extracts. In O3-MS, PC
      molecules carried by mobile phase pass through a length of gas-permeable tubing
      surrounded by ozone vapor resulting in oxidative cleavage of double bonds. The
      characteristic aldehyde products are then directly analyzed by eletrospray
      ionization (ESI)-MS, allowing assignment of the double bond positions within the
      PC fatty acyl chains. The on-line 2D-LC method employs hydrophilic interaction
      chromatography as the first dimension to separate phospholipid classes and
      reversed phase chromatography in the second dimension to further separate PC
      molecular species. Thus, by combing the separation power of 2D-LC with in-line O3
      MS (2D-LC/O3-MS), PC species in complex mixtures can be identified including the
      detailed structure of their two fatty acid chains. When the 2D-LC/O3-MS method
      was applied to a rat liver phospholipid extract, 19 PC molecular species were
      identified with fatty acid isomers unambiguously assigned. 

PMID- 24894112
TI  - Mucin-based stationary phases as tool for the characterization of drug-mucus
      interaction.
AB  - Mucin glycoproteins belong to a class of high molecular weight, heavy
      glycosylated, proteins that together with water, salts and lipids constitute
      mucous secretions. Particular disease states (e.g. obstructive chronic bronchitis
      and ovarian tumor) are known to modify the composition and the thickness of those
      barriers. Therefore, it is important to address whether the absorption of
      potential drug candidates to be administered is influenced by the presence of
      interaction with this class of proteins. Typically, the methods adopted to
      characterize drug-protein interaction are dialysis, ultrafiltration and gel
      filtration. Besides these, bio-affinity chromatographic methods have demonstrated
      to be valuable tools offering the advantageous characteristics such as
      simplicity, efficiency, high-throughput capability and robustness. The present
      contribution reports on the synthesis and analytical characterization of a new
      chromatographic stationary phase based on covalently immobilized mucin and
      explores the use of LC-UV affinity zonal chromatography as a tool to screen drugs
      for their affinity to mucin. A series of different binding chemistries for the
      covalent linkage of mucin to silica-based supports as well as distinct
      immobilization protocols (static and dynamic) have been evaluated in order to
      optimize surface coverage. Resultant stationary phases have been characterized
      chromatographically by studying the effect of mobile phase and analyte structure
      on the distribution and retention of test compounds. As conclusive study, we
      report the evaluation of the retention characteristics of 41 drug-like compounds
      (having heterogeneous chemical properties) for their interaction with this novel
      stationary phase. 

PMID- 24894113
TI  - Negative correlation of CD34+ cells with blood-brain barrier permeability
      following traumatic brain injury in a rat model.
AB  - OBJECTIVE: TBI causes localized cerebral ischemia that, in turn, is accompanied
      by both changes in BBB permeability and recruitment of CD34(+) cells to the
      injured tissue. However, it remains unknown whether CD34(+) cell recruitment is
      linked to BBB permeability. This study is a preliminary investigation into
      possible correlations between CD34(+) cell recruitment and BBB permeability
      following TBI in a rat model. METHODS: Male SD rats were subjected to mild fluid
      percussion injury. BBB permeability was assessed by measuring extrinsic EB dye
      extravasation and endogenous EBA expression at days 1, 3, 5, 7, and 12 post
      injury. The number of CD34(+) cells in the damaged tissue was analyzed by
      immunohistochemistry at each time point. RESULTS: EB dye extravasation reached a
      peak at day 3 following TBI, while EBA expression displayed the reverse profile.
      Accumulation of CD34(+) cells in injured brain tissue was evident at five days
      post injury. It revealed a negative linear correlation between CD34(+) cell and
      BBB permeability. CONCLUSIONS: The negative linear correlation between CD34(+)
      cell recruitment and BBB permeability following TBI provides a support for
      further study of CD34(+) cell transplantation for BBB repair after TBI.

PMID- 24894114
TI  - Genetic and ethnohistoric evidence suggest current Native American population
      datasets in the FBI's CODIS database are not sufficiently representative.

PMID- 24894115
TI  - Green light for liver function monitoring using indocyanine green? An overview of
      current clinical applications.
AB  - The dye indocyanine green is familiar to anaesthetists, and has been studied for
      more than half a century for cardiovascular and hepatic function monitoring. It
      is still, however, not yet in routine clinical use in anaesthesia and critical
      care, at least in Europe. This review is intended to provide a critical analysis
      of the available evidence concerning the indications for clinical measurement of
      indocyanine green elimination as a diagnostic and prognostic tool in two areas:
      its role in peri-operative liver function monitoring during major hepatic
      resection and liver transplantation; and its role in critically ill patients on
      the intensive care unit, where it is used for prediction of mortality, and for
      assessment of the severity of acute liver failure or that of intra-abdominal
      hypertension. Although numerous studies have demonstrated that indocyanine green
      elimination measurements in these patient populations can provide diagnostic or
      prognostic information to the clinician, 'hard' evidence - i.e. high-quality
      prospective randomised controlled trials - is lacking, and therefore it is not
      yet time to give a green light for use of indocyanine green in routine clinical
      practice. 

PMID- 24894117
TI  - Facial tremor in dystonia.
AB  - BACKGROUND: Tremor of the upper/middle part of the face, including the perinasal
      region and the forehead has been very rarely described in some patients with
      Parkinson's disease or Essential Tremor. It has not yet been reported in patients
      with idiopathic dystonia. METHODS: We describe here a series of 8 patients with
      common forms of idiopathic focal/segmental dystonia with tremor involving the
      upper/middle part of the face, along with demonstrative videos and
      electrophysiological recordings. RESULTS: The distribution of the tremor was
      confined to the face in two patients, whereas in six patients tremor was also
      evident either in the head/lower part of the face or in their upper limbs.
      Electrophysiological recordings disclosed a slightly irregular tremor with a
      frequency at about 3-5 Hz. CONCLUSIONS: A number of patients with classical forms
      of dystonia can show a tremor involving the upper/middle part of the face.

PMID- 24894116
TI  - Oxidized DJ-1 as a possible biomarker of Parkinson's disease.
AB  - Parkinson's disease is a progressive, age-related, neurodegenerative disorder,
      and oxidative stress is an important mediator in its pathogenesis. DJ-1 is a
      causative gene of a familial form of Parkinson's disease, namely PARK7, and plays
      a significant role in antioxidative defense to protect the cells from oxidative
      stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position
      106, Cys-106, under oxidative stress. The critical role of Cys-106 in the
      biological function of DJ-1 has been demonstrated, and recent studies indicate
      that DJ-1 acts as a sensor of oxidative stress by regulating the gene expression
      of antioxidative defense. Specific antibodies against Cys-106-oxidized DJ-1 have
      been developed, and the generation of oxidized DJ-1 in cellular and animal models
      of Parkinson's disease has been investigated. This review focuses on the role of
      DJ-1 in antioxidative defense and the importance of oxidizable Cys-106 in its
      function. The significance of the identification of early-phase Parkinson's
      disease biomarkers and the nature of oxidized DJ-1 as a biomarker for Parkinson's
      disease are discussed here. 

PMID- 24894119
TI  - A retrospective study of the clinical and electrophysiological characteristics of
      32 patients with orthostatic myoclonus.
AB  - OBJECTIVES: To review the electrophysiological and clinical characteristics of 32
      patients with orthostatic myoclonus (OM), a relatively newly identified movement
      disorder, and compare these characteristics to those of primary orthostatic
      tremor (OT) patients and patients with similar gait and balance complaints
      without either hyperkinesia diagnosed during the same 30-month period. METHODS:
      The database of the Mayo Clinic Florida Movement Disorders Electrophysiology
      Laboratory (MDEL) was searched for all patients referred for possible OM or OT
      from 6/2010 to 12/2012. All available clinical records and archived surface
      electromyographical data for these patients were reviewed and analyzed. RESULTS:
      32 patients with OM (mean age 74 years), 8 with primary OT (mean age 71), and 55
      with neither orthostatic hyperkinesia (NOH) (mean age 68) were identified. All OT
      patients and 84% each of OM and NOH patients complained of involuntary leg
      movements while standing, e.g., "shaking," "trembling," or "jerking." All OM and
      OT patients experienced symptomatic and electrophysiological abatement or
      attenuation of their leg hyperkinesias by leaning forward onto an object while
      standing. CONCLUSIONS: OM has some similarities to OT, including causing "shaky
      legs" subjectively in standing older patients. Novel data from this work include
      that, as in OT, OM essentially abates when patients remove their weight from
      their legs. This shared isometric phenomenon may reflect that OT and OM are on a
      pathophysiological continuum. Further, many patients who complain of their legs
      "shaking" while standing may have neither OT nor OM. Surface electromyography may
      be a useful adjunct in extrapolating patients complaining of "shaky legs."

PMID- 24894118
TI  - Multiple system atrophy as emerging template for accelerated drug discovery in
      alpha-synucleinopathies.
AB  - There is evidence that the alpha-synucleinopathies Parkinson's disease (PD) and
      the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple
      levels. Both disorders are characterized by deposition of abnormally
      phosphorylated fibrillar alpha-synuclein within the central nervous system
      suggesting shared pathophysiological mechanisms. Despite the considerable
      clinical overlap in the early disease stages, MSA-P, in contrast to PD, is fatal
      and rapidly progressive. Moreover recent clinical studies have shown that
      surrogate markers of disease progression can be quantified easily and may
      reliably depict the rapid course of MSA. We therefore posit that, MSA-P may be
      exploited as a filter barrier in the development of disease-modifying therapeutic
      strategies targeting common pathophysiological mechanisms of alpha
      synucleinopathies. This approach might reduce the number of negative phase III
      clinical trials, and, in turn, shift the available resources to earlier
      development stages, thereby increasing the number of candidate compounds
      validated. 

PMID- 24894120
TI  - The "dual-pathway" strategy after acute coronary syndrome: rivaroxaban and
      antiplatelet agents in the ATLAS ACS 2-TIMI 51 trial.
AB  - Acute coronary syndrome (ACS) is a medical emergency often associated with an
      occlusive coronary event with consequent myocardial underperfusion. Patients
      require immediate antiplatelet therapy and long-term antithrombotic prophylaxis
      to reduce the risk of recurrence. Acetylsalicylic acid (ASA) alone or in
      combination with a platelet P2Y12 inhibitor (dual antiplatelet therapy [DAPT])
      has become the clinically accepted antithrombotic prophylaxis for patients post
      ACS. Historically, studies assessing the utility of adding oral anticoagulants
      (OACs) have not demonstrated a clinical benefit with regard to acceptable
      bleeding risk. Studies with vitamin K antagonists (VKAs) such as warfarin
      demonstrated a potential to reduce the risk of subsequent death by reinfarction
      but this benefit was offset by increases in bleeding. Results from studies of two
      targeted non-VKA OACs also proved disappointing, with little or no apparent
      reduction in the rate of ischemic events seen. However, the recent ATLAS studies
      assessing rivaroxaban (an oral factor Xa inhibitor) in patients with ACS
      demonstrated a reduction in the composite endpoint of deaths from cardiovascular
      causes, myocardial infarction (MI), or stroke, and a reduction in the rate of
      stent thrombosis. This review provides an overview of the pivotal studies in
      which the addition of OACs to antiplatelet therapy (the so-called "dual-pathway"
      approach) has been investigated for the management of patients post-ACS and
      considers the results of the ATLAS studies and their potential impact on the
      management of patients after an acute event. 

PMID- 24894121
TI  - Part II: The 50 degrees /60 degrees  fibular tunnel trajectory for posterolateral
      corner reconstruction in a cadaver model.
AB  - PURPOSE: Using data from our MRI study, we found that a tunnel oriented 50
      degrees  externally rotated and 60 degrees  cephalad would better connect the
      fibular collateral ligament (FCL) insertion to the popliteofibular ligament (PFL)
      insertion as compared to a traditional anterior-to-posterior (A-P) fibular
      tunnel. The purpose of this study was to test that finding in a cadaver model.
      METHODS: In eight cadaver knee pairs (16 knees), a guide pin was driven from the
      fibular FCL insertion point in a 50 degrees  externally rotated and 60 degrees 
      cephalad trajectory in 8 knees, and in a traditional A-P trajectory in the
      contralateral 8 knees. Proximity of the pin to the native PFL insertion, the
      peroneal and tibial nerves was measured, followed by drilling over the guide pin
      and measuring the remaining fibular bone stock. RESULTS: In comparison with the A
      P fibular tunnel technique, the 50 degrees /60 degrees  technique resulted in a
      fibular exit point significantly closer to the native PFL insertion (p < 0.01).
      Both techniques were safe with regard to the tibial and peroneal nerves. There
      were no instances of fibular wall blowout in either technique; however, there was
      less superior bone remaining in the 50 degrees /60 degrees  technique (p < 0.04).
      CONCLUSION: In a cadaveric model, the 50 degrees /60 degrees  technique for PLC
      reconstruction resulted in a more anatomic-based tunnel than an A-P fibular
      tunnel.

PMID- 24894122
TI  - Full-thickness rotator cuff tears in patients younger than 55 years: clinical
      outcome of arthroscopic repair in comparison with older patients.
AB  - PURPOSE: The purpose of this study was to examine whether younger patients had a
      similar response to repair of a full-thickness rotator cuff tear (RCT) as older
      patients. METHODS: A secondary analysis was conducted of prospectively collected
      data of patients with full-thickness RCTs. Patients were categorized into
      patients <55 years of age and patients 55 and older. Patient-related outcome
      measures of disability at 2 years following surgery were the Short Western
      Ontario Rotator Cuff (Short WORC), American Shoulder and Elbow Surgeon's (ASES)
      assessment form, and absolute Constant-Murley score (ACMS). RESULTS: Review of
      the database between 2001 and 2011 identified 344 patients (median age 62, range
      24-90). Of these, 83 (24 %) patients were younger than 55 years of age (median
      age 48, range 24-54) and 261 (76 %) were in the older age group (median age 66,
      range 55-90). The median follow-up was 24 months (range 23-25). Patients in the
      younger age group had a higher prevalence of traumatic events (p = 0.02), had
      sustained more work-related injuries (p < 0.0001), and had a higher ratio of
      smaller tears (p = 0.0001). No difference was seen between groups with respect to
      post-operative scores of Short WORC, ASES, or ACMS. Pre-operative scores, having
      a work-related claim, increased tear size, and concomitant procedures affected
      the 2-year outcome scores. CONCLUSION: This study shows that younger patients
      with full-thickness RCTs who undergo an arthroscopic repair do as well as older
      individuals regardless of the measure used to document their recovery. LEVEL OF
      EVIDENCE: Retrospective outcome study, Level II.

PMID- 24894123
TI  - The role of the deep medial collateral ligament in controlling rotational
      stability of the knee.
AB  - PURPOSE: The tibial insertion of the deep medial collateral ligament (dMCL) is
      frequently sacrificed when the proximal tibial cut is performed during total knee
      arthroplasty. The role of the dMCL in controlling the knee's rotational stability
      is still controversial. The aim of this study was to quantify the rotational
      laxity induced by an isolated lesion of the dMCL as it occurs during tibial
      preparation for knee arthroplasty. METHODS: An isolated resection of the deep MCL
      was performed in 10 fresh-frozen cadaver knees. Rotational laxity was measured
      during application of a standard 5.0 N.m rotational torque. Maximal tibial
      rotation was measured at different knee flexion angles using an image-guided
      navigation system (Medivision Surgetics system, Praxim, Grenoble, France) before
      and after dMCL resection. RESULTS: In all cases, internal and external tibial
      rotation increased after dMCL resection. Total rotational laxity increased
      significantly for all knee flexion angles, with an average difference of +7.8
      degrees  (SD 5.7) with the knee in extension, +8.9 degrees  (SD 1.9) in 30
      degrees  flexion, +7 degrees  (SD 2.9) in 60 degrees  flexion and +5.3 degrees 
      (SD 2.8) in 90 degrees  flexion. CONCLUSIONS: Sacrificing the tibial insertion of
      the deep MCL increases rotational laxity of the knee by 5 degrees -9 degrees ,
      depending on the knee flexion angle. Based on our findings, new surgical
      techniques and implants that preserve the dMCL insertion such as tibial inlay
      components should be developed. Further clinical evaluations are necessary.

PMID- 24894124
TI  - Application of retinoic acid to obtain osteocytes cultures from primary mouse
      osteoblasts.
AB  - The need for osteocyte cultures is well known to the community of bone
      researchers; isolation of primary osteocytes is difficult and produces low cell
      numbers. Therefore, the most widely used cellular system is the osteocyte-like
      MLO-Y4 cell line. The method here described refers to the use of retinoic acid to
      generate a homogeneous population of ramified cells with morphological and
      molecular osteocyte features. After isolation of osteoblasts from mouse calvaria,
      all-trans retinoic acid (ATRA) is added to cell medium, and cell monitoring is
      conducted daily under an inverted microscope. First morphological changes are
      detectable after 2 days of treatment and differentiation is generally complete in
      5 days, with progressive development of dendrites, loss of the ability to produce
      extracellular matrix, down-regulation of osteoblast markers and up-regulation of
      osteocyte-specific molecules. Daily cell monitoring is needed because of the
      inherent variability of primary cells, and the protocol can be adapted with
      minimal variation to cells obtained from different mouse strains and applied to
      transgenic models. The method is easy to perform and does not require special
      instrumentation, it is highly reproducible, and rapidly generates a mature
      osteocyte population in complete absence of extracellular matrix, allowing the
      use of these cells for unlimited biological applications. 

PMID- 24894125
TI  - Aerogel microspheres from natural cellulose nanofibrils and their application as
      cell culture scaffold.
AB  - We demonstrated that ultralight pure natural aerogel microspheres can be
      fabricated using cellulose nanofibrials (CNF) directly. Experimentally, the CNF
      aqueous gel droplets, produced by spraying and atomizing through a steel nozzle,
      were collected into liquid nitrogen for instant freezing followed by freeze
      drying. The aerogel microspheres are highly porous with bulk density as low as
      0.0018 g cm(-3). The pore size of the cellulose aeogel microspheres ranges from
      nano- to macrometers. The unique ultralight and high porous structure ensured
      high moisture (~90 g g(-1)) and water uptake capacity (~100 g g(-1)) of the
      aerogel microspheres. Covalent cross-linking between the native nanofibrils and
      cross-linkers made the aerogel microspheres very stable even in a harsh
      environment. The present study also confirmed this kind of aerogel microspheres
      from native cellulose fibers can be used as cell culture scaffold.

PMID- 24894126
TI  - Diagnostic evaluation and short-term outcome as indicators of long-term prognosis
      in horses with findings suggestive of inflammatory bowel disease treated with
      corticosteroids and anthelmintics.
AB  - BACKGROUND: Recurrent colic and unexplained weight loss despite good appetite and
      adequate feeding and management practices are common conditions in the horse.
      However, little information has been published on the systematic diagnostic
      evaluation, response to treatment, prognostic factors or outcome of either
      presentation. The aims of this study were to 1) identify possible prognostic
      indicators and 2) report the short- and long-term response to treatment with
      corticosteroid therapy of a variety of horses with a presumptive diagnosis of
      inflammatory bowel disease (IBD). Thirty-six horses with a history of recurrent
      colic and/or unexplained weight loss were screened with a detailed clinical,
      clinicopathological and diagnostic imaging examination. Twenty horses were
      subsequently selected that had findings consistent with inflammatory bowel
      disease based on the fulfilment of one or more of the following additional
      inclusion criteria: hypoproteinaemia, hypoalbuminaemia, malabsorption, an
      increased intestinal wall thickness on ultrasonographic examination or
      histopathological changes in rectal biopsy. These 20 horses were treated with a
      standardized larvicidal anthelmintic regime and a minimum of three weeks of
      corticosteroid therapy. RESULTS: The initial response to treatment was good in
      75% (15/20) of horses, with a 3-year survival rate of 65% (13/20). The overall 3
      year survival in horses that responded to initial treatment (12/15) was
      significantly higher (P = 0.031) than in those that did not respond to initial
      treatment (1/5). The peak xylose concentration was significantly (P = 0.048)
      higher in survivors (1.36 +/- 0.44 mmol/L) than non-survivors (0.94 +/- 0.36
      mmol/L). CONCLUSIONS: The overall prognosis for long-term survival in horses with
      a presumptive diagnosis of IBD appears to be fair to moderate, and the initial
      response to anthelmintic and corticosteroid therapy could be a useful prognostic
      indicator. The findings of the present study suggest that a low peak xylose
      concentration in absorption testing is associated with a less favourable
      prognosis, supporting the use of this test.

PMID- 24894127
TI  - Differences in job stress experienced by female and male Japanese psychiatric
      nurses.
AB  - In psychiatric nursing, female nurses tend to spend more time building rapport
      with patients and developing cooperative working relationships with colleagues;
      they encounter more sexual harassment by patients. In contrast, male nurses
      respond to aggressive patients and tend to resist physically caring for female
      patients; they encounter more physical and verbal assault from patients. These
      gender differences might result in differences in job-related stress. We
      quantitatively examined gender differences in psychiatric nurses' job stress. The
      Psychiatric Nurse Job Stressor Scale and the Stress Reaction Scale of the Brief
      Job Stress Questionnaire were administered to 159 female and 85 male Japanese
      psychiatric nurses. The results indicated that female nurses had significantly
      higher stress levels than males related to psychiatric nursing ability, attitude
      towards nursing, and stress reactions of fatigue and anxiety. Moreover, the
      factors affecting stress reactions differed somewhat between sexes. In
      particular, male nurses reported that greater irritability was affected by
      patients' attitudes. Their anxiety and somatic symptoms were affected by their
      attitude towards nursing, and depressed mood was affected by psychiatric nursing
      ability. Knowledge of these differences can lead to better mental health-care
      interventions for psychiatric nurses. 

PMID- 24894128
TI  - Flank muscle volume changes after open and laparoscopic partial nephrectomy.
AB  - PURPOSE: To determine the occurrence of flank symptoms, flank muscle atrophy,
      bulge, and hernia formation after open and laparoscopic partial nephrectomy
      (LPN). PATIENTS AND METHODS: Our prospective Institutional Review Board-approved
      database was queried to identify 50 consecutive patients who were treated with
      open partial nephrectomy (OPN) and 50 consecutive patients who were treated with
      LPN between September 2006 and May 2008. Study patients had: Solitary clinical T1
      renal tumor, preoperative and >=6 month postoperative CT scan performed at our
      institution, and a confirmed renal-cell carcinoma on the final pathology report.
      Patients with previous abdominal surgery and neuromuscular disorders were
      excluded. Oncocare software was used to measure abdominal wall musculature on
      preoperative and postoperative CT scan. Bilateral flanks were compared for muscle
      volume, bulge, and hernia. Patients were administered a phone questionnaire to
      assess postoperative flank symptoms. RESULTS: No statistical significant
      difference was found in the demographics between the two groups. Median age
      (range) was 59.9 years (20.6-80.7) in the OPN group and 57.5 years (25-78) in the
      LPN group (P=0.89). Median (range) body mass index and American Society of
      Anesthesiologists scores were similar between the two groups. On CT scans, median
      percent variation (range) in abdominal wall muscle volume was significantly
      greater in the OPN group: -1.03% (-31.4-1.5) vs-0.39% (-5.2-1.8) (P=0.006). The
      median extent of flank bulge on CT scans (range) was also greater in the OPN
      group: 0.75 cm (-1.9-7.6) vs 0 cm (-2.7-2.8) (P=0.0004). The OPN group was also
      more symptomatic, including paresthesia 48% vs 8% (P=0.0053); numbness 44% vs 0%
      (P=0.002); and flank bulge 57% vs 12% (P=0.007). CONCLUSIONS: Minimally invasive
      partial nephrectomy has lesser deleterious impact on flank muscle volume compared
      with OPN with fewer symptoms of flank bulge, paresthesia, and numbness.

PMID- 24894129
TI  - Motor abilities and anthropometrics in youth cross-country skiing.
AB  - The purposes were to validate whether general motor abilities and anthropometrics
      are determinants of youth cross-country (XC) skiing performance; evaluate gender
      specific differences; and to establish noninvasive diagnostics. Fifty-one youth
      XC skiers (34 boys; 13.8 +/- 0.6 years and 17 girls; 13.4 +/- 0.9 years)
      performed motor skill and laboratory tests, and anthropometric data were
      collected and correlated with XC skiing performance. Anthropometrics and maturity
      status were related to boys but not to girls XC skiing performance. Push-ups and
      20-m sprint were correlated to XC skiing performance in both boys and girls. XC
      skiing performance of boys was predominantly influenced by upper body and trunk
      strength capacities (medicine ball throw, push-ups, and pull-ups) and jumping
      power (standing long and triple jump), whereas XC skiing of girls was mainly
      influenced by aerobic capacities (3000-m run). Laboratory measures did not reveal
      greater correlations to XC skiing performance compared with simple test concepts
      of speed, strength, and endurance. Maturity was a major confounding variable in
      boys but not girls. Use of noninvasive simple test concepts for determination of
      upper body strength, speed, and endurance represent practicable support for ski
      clubs, schools, or skiing federations in the guidance and evaluation of young
      talent, being aware of the effect of maturity especially in boys.

PMID- 24894130
TI  - Response to: 'when man got his mtDNA deletions?'.

PMID- 24894131
TI  - Experimental infection of Rhipicephalus sanguineus with Ehrlichia chaffeensis.
AB  - Ehrlichia chaffeensis, the etiologic agent of human monocytic ehrlichiosis, is a
      tick-borne rickettsial pathogen that is infective to a wide range of mammals,
      including dogs and people. Amblyomma americanum, the lone star tick, is
      considered the primary vector of E. chaffeensis, but this pathogen has been
      detected in other tick species, including the brown dog tick, Rhipicephalus
      sanguineus. We hypothesized that the Arkansas strain of E. chaffeensis is
      infective to R. sanguineus, and used a novel PCR assay to test for acquisition of
      this pathogen by R. sanguineus and A. americanum ticks that were simultaneously
      fed on experimentally infected dogs. Although E. chaffeensis was not frequently
      detected in peripheral blood of these dogs, the pathogen was detected in both
      tick species and in canine lung, kidney, lymph node, bone marrow and frontal lobe
      samples. One dog (AFL) was maintained for several years, and ticks again acquired
      E. chaffeensis from this dog 566 days after intradermal inoculation with E.
      chaffeensis, but the pathogen was not detected in ticks fed on the same dog at
      764 or 1086 days after the intradermal inoculation. 

PMID- 24894133
TI  - Carriage and acquisition rates of Clostridium difficile in hospitalized horses,
      including molecular characterization, multilocus sequence typing and
      antimicrobial susceptibility of bacterial isolates.
AB  - Clostridium difficile has been identified as a significant agent of diarrhoea and
      enterocolitis in both foals and adult horses. Hospitalization, antibiotic therapy
      or changes in diet may contribute to the development of C. difficile infection.
      Horses admitted to a care unit are therefore at greater risk of being colonized.
      The aim of this study was to investigate the carriage of C. difficile in
      hospitalized horses and the possible influence of some risk factors in
      colonization. During a seven-month period, faecal samples and data relating the
      clinical history of horses admitted to a veterinary teaching hospital were
      collected. C. difficile isolates were characterized through toxin profiles,
      cytotoxicity activity, PCR-ribotyping, antimicrobial resistance and multilocus
      sequence typing (MLST). Ten isolates were obtained with a total of seven
      different PCR-ribotypes, including PCR-ribotype 014. Five of them were identified
      as toxinogenic. A high resistance to gentamicin, clindamycin and ceftiofur was
      found. MLST revealed four different sequencing types (ST), which included ST11,
      ST26, ST2 and ST15, and phylogenetic analysis showed that most of the isolates
      clustered in the same lineage. Clinical history suggests that horses frequently
      harbour toxigenic and non-toxigenic C. difficile and that in most cases they are
      colonized regardless of the reason for hospitalization; the development of
      diarrhoea is more unusual. 

PMID- 24894132
TI  - Inactivated vaccine with adjuvants consisting of pattern recognition receptor
      agonists confers protection against avian influenza viruses in chickens.
AB  - Use of adjuvant containing pathogen pattern recognition receptor agonists is one
      of the effective strategies to enhance the efficacy of licensed vaccines. In this
      study, we investigated the efficacy of avian influenza vaccines containing an
      adjuvant (CVCVA5) which was composed of polyriboinosinic polyribocytidylic,
      resiquimod, imiquimod, muramyl dipeptide and levomisole. Avian influenza vaccines
      adjuvanted with CVCVA5 were found to induce significantly higher titers of
      hemagglutiniton inhibition antibodies (P<=0.01) than those of commercial vaccines
      at 2-, 3- and 4-week post vaccination in both specific pathogen free (SPF)
      chickens and field application. Furthermore, virus shedding was reduced in SPF
      chickens immunized with H9-CVCVA5 vaccine after H9 subtype heterologous virus
      challenge. The ratios of both CD3(+)CD4(+) and CD3(+)CD8(+) lymphocytes were
      slowly elevated in chickens immunized with H9-CVCVA5 vaccine. Lymphocytes
      adoptive transfer study indicates that CD8(+) T lymphocyte subpopulation might
      have contributed to improved protection against heterologous virus challenge.
      Results of this study suggest that the adjuvant CVCVA5 was capable of enhancing
      the potency of existing avian influenza vaccines by increasing humoral and
      cellular immune response. 

PMID- 24894134
TI  - Field vaccinated chickens with low antibody titres show equally insufficient
      protection against matching and non-matching genotypes of virulent Newcastle
      disease virus.
AB  - Newcastle disease (ND) is a severe threat to the poultry industry and is caused
      by virulent strains of Newcastle disease virus (NDV). Many countries maintain a
      vaccination policy, but NDV is rapidly evolving as shown by the discovery of
      several new genotypes in the last decades. We tested the efficacy of the
      currently used classical commercial ND vaccine based on the genotype II strain
      VG/GA, applied under standard field conditions, against outbreak strains. Field
      vaccinated broilers were challenged with four different viruses belonging to
      genotype II, V or VII. A large proportion of field vaccinated broilers showed
      suboptimal immunity and the protection level against early and recent NDV
      isolates was dramatically low. Furthermore, there were no significant differences
      in protection afforded by a genotype II vaccine against a genotype II virus
      challenge compared to a challenge with viruses belonging to the other genotypes.
      This study suggests that the susceptibility of vaccinated poultry to NDV
      infection is not the result of vaccine mismatch, but rather of poor vaccination
      practices. 

PMID- 24894135
TI  - Animal models of exercise and obesity.
AB  - Animal models have been invaluable in the conduct of nursing research for the
      past 40 years. This review will focus on specific animal models that can be used
      in nursing research to study the physiologic phenomena of exercise and obesity
      when the use of human subjects is either scientifically premature or
      inappropriate because of the need for sampling tissue or the conduct of
      longitudinal studies of aging. There exists an extensive body of literature
      reporting the experimental use of various animal models, in both exercise science
      and the study of the mechanisms of obesity. Many of these studies are focused on
      the molecular and genetic mechanisms of organ system adaptation and plasticity in
      response to exercise, obesity, or both. However, this review will narrowly focus
      on the models useful to nursing research in the study of exercise in the clinical
      context of increasing performance and mobility, atrophy and bedrest, fatigue, and
      aging. Animal models of obesity focus on those that best approximate clinical
      pathology. 

PMID- 24894136
TI  - Thermoregulation: cytokines involved in fever and exercise.
AB  - The study of fever has provided important models in understanding the cells,
      chemical messengers, and anatomic structures that are involved in inflammation
      and thermoregulation as a result of infection, stress, or trauma. After contact
      with a pathogen or an inflammatory stimulus, cells are activated to produce
      endogenous pyrogens called cytokines. Cytokine functions include a cascade of
      nonspecific immune responses by target leukocytes and reticuloendothelial cells
      inducing the synthesis of acute phase proteins by the liver, direct pyrogenic
      activities via the supraoptic nuclei and the hypothalamus to increase the
      thermoregulatory set-point (and, thus, induce fever), and a wide spectrum of
      additional immune effects. 

PMID- 24894138
TI  - Physical activity intervention studies and their relationship to body composition
      in healthy women.
AB  - Engaging in regular physical activity is a key component for maintaining a
      healthy weight and preventing overweight and obesity. Obesity continues to be a
      concern globally, especially for women, and women are less physically active than
      men. This systematic review examined current research on physical activity
      interventions designed for healthy community dwelling women and assessed the
      effects of those interventions on physical activity and body composition. Three
      author-developed data collection tools were used to extract and examine study
      variables. For studies with suitable data, effect sizes were obtained. The
      initial search identified 1,406 titles published between 2000 and 2012, of which
      40 randomized clinical trials met inclusion criteria. Of these 40 studies, 16 had
      a physical activity intervention that did not have a diet component and 24 had a
      physical activity intervention along with a diet component. The overall weighted
      mean effect was d = .21, 95% CI [0.06, 0.36] for physical activity outcomes (n =
      18 studies) and d = -.16, 95% CI [-0.22, -0.09] for body composition outcomes (n
      = 24 studies). Both physical activity interventions without and with a diet
      component were effective in promoting physical activity and improving body
      composition. Physical activity interventions without a diet component were more
      effective than physical activity interventions with a diet component at promoting
      physical activity. The most effective interventions need to be adapted for
      dissemination into practice. 

PMID- 24894139
TI  - The effects of exercise during pregnancy: theories, evidence, and interventions.
AB  - Physical activities provide women a way to improve their health and intervene in
      disease processes during pregnancy. This chapter briefly describes
      pathophysiological models and then examines current research on the effects of
      physical activity on prevention and treatment of gestational diabetes and
      preeclampsia. The chapter then reviews cognitive behavioral theories and current
      literature on the effects of behavioral interventions on physical activity in
      pregnancy. The literature helps to explain the pathophysiological mechanisms
      through which physical activity mediates disease processes and the behavioral
      interventions through which physical activity can be introduced and sustained
      during pregnancy. Throughout the chapter, both pathophysiological models and
      behavioral theories are viewed as part of a socioecologic model that encompasses
      pregnancy and physical activity. 

PMID- 24894140
TI  - Using function-focused care to increase physical activity among older adults.
AB  - Despite the known benefits of physical activity for older adults, adherence to
      regular physical activity recommendations is poor. Less than half of adults in
      this country meet physical activity recommendations with reasons for lack of
      adherence including such things as access, motivation, pain, fear, comorbidities,
      among others. To overcome these challenges, function-focused care was developed.
      Function-focused care is a philosophy of care that focuses on evaluating the
      older adult's underlying capability with regard to function and physical activity
      and helping him or her optimize and maintain physical function and ability and
      continually increase time spent in physical activity. Examples of function
      focused care include such things as using verbal cues during bathing, so the
      older individual performs the tasks rather than the caregiver bathing the
      individual; walking a resident or patient to the bathroom rather than using a
      urinal, or taking a resident to an exercise class. There are now over 20 studies
      supporting the benefits of function-focused care approaches across all settings
      and different types of patient groups (i.e, those with mild versus moderate-to
      severe cognitive impairment). The approaches for implementation of function
      focused care have also been well supported and have moved beyond establishing
      effectiveness to considering dissemination and implementation of this approach
      into real world clinical settings. The process of dissemination and
      implementation has likewise been articulated and supported, and ongoing work
      needs to continue in this venue across all care settings. 

PMID- 24894137
TI  - Overweight and obesity in youth with type 1 diabetes.
AB  - Overweight and obesity in youth with type 1 diabetes (T1D) is now prevalent and
      accounts for significant health consequences, including cardiovascular
      complications and dual diagnosis of type 2 diabetes. Physical activity and
      lifestyle are modifiable and play an important role in the prevention and
      management of excessive weight, but it is unclear how these factors relate to
      overweight and obese youth with T1D. Thus, a systematic review was conducted to
      examine how physical activity, sedentary behavior, sleep, and diet are related to
      overweight/obesity in youth with T1D. Seven observational and intervention
      studies published between 1990 and 2013 were included in the review. Prevalence
      of overweight ranged from 12.5% to 33.3%. Overweight in youth with T1D was
      associated with infrequent napping, increased screen time, and skipping breakfast
      and dinner but was not related to time engaged in physical activity. Weight
      related interventions indicated modest weight loss along with improved glycemic
      control. In light of this review, there is a need for high quality research that
      examines all levels of activity in youth with T1D to identify lifestyle
      modification targets for weight prevention and management. 

PMID- 24894141
TI  - Hispanic women and physical activity: an integrative review.
AB  - Hispanics/Latinos represent the largest, fastest growing, and youngest minority
      group in the United States. Although data suggest that most Hispanics/Latinos in
      the United States tend to be in better health than non-Hispanic Whites (the so
      called "Hispanic Paradox"), these relative advantages in health status decrease
      markedly with the number of years of residence in the United States. Hispanic
      women or Latinas, in general, report less than recommended levels of physical
      activity (PA), putting them at greater risk for the development of cardiovascular
      disease (CVD) and other chronic illnesses associated with sedentary lifestyles. 

PMID- 24894142
TI  - Exercise therapy in individuals with chronic kidney disease: a systematic review
      and synthesis of the research evidence.
AB  - Chronic kidney disease (CKD) is becoming a serious health problem throughout the
      world and is one of the most potent known risk factors for cardiovascular disease
      (CVD) which is considered the leading cause of morbidity and mortality in this
      cohort of patients. Additional independent risk factors for poor health outcomes
      among many include diabetes, physical inactivity and physical dysfunction.
      Physical inactivity partly contributes to the accelerated deterioration of
      physical function in people in all stages of CKD, to levels that significantly
      impact on clinically and patient important outcomes such as morbidity,
      employment, quality of life (QoL) and ultimately survival. Ongoing research aims
      to determine the effectiveness and impact of exercise rehabilitation on
      reducing/managing the risk of CVD, alleviating physical function limitations,
      preventing disability and enhancing QoL. Current research also aims to elucidate
      the mechanisms via which exercise therapy may contribute to clinically relevant
      benefits. 

PMID- 24894143
TI  - Effect of exercise on cardiac and metabolic outcomes in people living with HIV.
AB  - Poorly controlled HIV infection and antiretroviral therapy, especially the use of
      protease inhibitors, are among the causes that contribute to the development of
      cardiovascular disease in people living with HIV (PLWH). Poor lifestyle choices
      (smoking, lack of physical activity, poor diet) and individual factors such as
      high stress, physical or emotional trauma, depression, and so forth contribute to
      the overall risk of developing cardiovascular disease. The purpose of this review
      was to critically evaluate the more recent aerobic and resistance exercise
      studies and their impact on cardiovascular and metabolic risk factors in PLWH. 

PMID- 24894144
TI  - Interventions to increase physical activity in people with COPD: systematic
      review.
AB  - People with chronic obstructive pulmonary disease (COPD) are very sedentary and
      this contributes to their health problems. The aim of this systematic review was
      to examine the effects of interventions designed to increase physical activity
      (PA) in people with COPD. Studies were included when PA was the primary outcome
      and measured objectively. Six databases were searched and 15 studies with a total
      of 761 subjects were identified that met inclusion criteria. Nine of the studies
      were quasi-experimental (QE) and six were randomized controlled trials (RCT).
      Interventions included pulmonary rehabilitation (n = 7), exercise only (n = 2),
      behavioral only (n = 2) and a combination of both behavioral and pulmonary
      rehabilitation/exercise interventions (n = 4). Methodological quality was
      evaluated using the Downs and Black checklist. The quality of the pulmonary
      rehabilitation studies was the lowest with a fair rating and the quality of
      exercise only studies was the highest with a good rating. Eight of the 15 studies
      demonstrated statistically significant increases in PA: two pulmonary
      rehabilitation (QE = 2), two exercise only (RCT = 2), two behavioral only (RCT =
      1, QE = 1), and two combined behavioral and pulmonary rehabilitation/exercise
      (RCT = 2). The magnitude of increase was modest in all but one study; and in many
      studies the increase in PA was not clinically meaningful. Longer interventions
      demonstrated a higher success rate and only three studies examined longer term
      effects of the interventions. Existing interventions are promising, but the small
      number of randomized controlled trials makes it difficult to draw conclusion.
      Further research is needed to identify a range of interventions that are
      effective and could be used to promote PA in people with COPD. 

PMID- 24894145
TI  - Exercise and cancer.
AB  - There are an estimated 13.7 million cancer survivors in the United States.
      Persistent and late effects of cancer therapy have contributed to an increased
      risk for co-morbid illness and higher all-cause mortality. Physical exercise is a
      targeted rehabilitative intervention following cancer therapy and a health
      promotion risk reduction intervention for patients as they transition into
      survivorship. This chapter provides a brief overview of the research on exercise
      and cancer survivor outcomes with a specific focus on randomized controlled
      trials (RCT) on the effects of exercise on body composition and bone health.
      There were 17 RCT trials that were identified with body composition outcomes.
      There was no change in weight in 16/17 trials, 4 reported decreases in percent
      fat mass and 2 reported increases in lean mass. Eight exercise trials were
      identified with bone outcomes, two of which had pharmacologic comparison arms.
      These trials demonstrated preservation of bone in the intervention group compared
      with loss in the usual care or placebo control group. The majority of trials were
      with breast cancer survivors, the largest survivor group. Many are overweight or
      obese at diagnosis; weight gain continues to increase after therapy; and
      treatment is associated with bone loss. The findings of the 25 trials reviewed
      suggest that exercise maintains weight and bone mass in a high risk population.
      However, differences in design, measurement of body composition and bone mass and
      lack of targeted exercise to the specific outcomes warrants additional research
      to improve the quality of life for survivors. 

PMID- 24894147
TI  - Aerobic or resistance exercise, used on a regular basis, has many benefits and
      few risks. Introduction.

PMID- 24894146
TI  - ROS and RNS signaling in skeletal muscle: critical signals and therapeutic
      targets.
AB  - The health of skeletal muscle is promoted by optimal nutrition and
      activity/exercise through the activation of molecular signaling pathways.
      Reactive oxygen species (ROS) or reactive nitrogen species (RNS) have been shown
      to modulate numerous biochemical processes including glucose uptake, gene
      expression, calcium signaling, and contractility. In pathological conditions,
      ROS/RNS signaling excess or dysfunction contributes to contractile dysfunction
      and myopathy in skeletal muscle. Here we provide a brief review of ROS/RNS
      chemistry and discuss concepts of ROS/RNS signaling and its role in physiological
      and pathophysiological processes within striated muscle. 

PMID- 24894148
TI  - Genome-Wide Association in Tomato Reveals 44 Candidate Loci for Fruit Metabolic
      Traits.
AB  - Genome-wide association studies have been successful in identifying genes
      involved in polygenic traits and are valuable for crop improvement. Tomato
      (Solanum lycopersicum) is a major crop and is highly appreciated worldwide for
      its health value. We used a core collection of 163 tomato accessions composed of
      S. lycopersicum, S. lycopersicum var cerasiforme, and Solanum pimpinellifolium to
      map loci controlling variation in fruit metabolites. Fruits were phenotyped for a
      broad range of metabolites, including amino acids, sugars, and ascorbate. In
      parallel, the accessions were genotyped with 5,995 single-nucleotide polymorphism
      markers spread over the whole genome. Genome-wide association analysis was
      conducted on a large set of metabolic traits that were stable over 2 years using
      a multilocus mixed model as a general method for mapping complex traits in
      structured populations and applied to tomato. We detected a total of 44 loci that
      were significantly associated with a total of 19 traits, including sucrose,
      ascorbate, malate, and citrate levels. These results not only provide a list of
      candidate loci to be functionally validated but also a powerful analytical
      approach for finding genetic variants that can be directly used for crop
      improvement and deciphering the genetic architecture of complex traits.

PMID- 24894150
TI  - Concerning iron balance in blood donors.

PMID- 24894149
TI  - Biological regulation of bone quality.
AB  - The ability of bone to resist fracture is determined by the combination of bone
      mass and bone quality. Like bone mass, bone quality is carefully regulated. Of
      the many aspects of bone quality, this review focuses on biological mechanisms
      that control the material quality of the bone extracellular matrix (ECM). Bone
      ECM quality depends upon ECM composition and organization. Proteins and signaling
      pathways that affect the mineral or organic constituents of bone ECM impact bone
      ECM material properties, such as elastic modulus and hardness. These properties
      are also sensitive to pathways that regulate bone remodeling by osteoblasts,
      osteoclasts, and osteocytes. Several extracellular proteins, signaling pathways,
      intracellular effectors, and transcription regulatory networks have been
      implicated in the control of bone ECM quality. A molecular understanding of these
      mechanisms will elucidate the biological control of bone quality and suggest new
      targets for the development of therapies to prevent bone fragility. 

PMID- 24894152
TI  - In memory of Janette Klingner.

PMID- 24894153
TI  - No influence of exogenous hyaluronan on the behavior of human cancer cells or
      endothelial cell capillary formation.
AB  - Hyaluronan (HA), a type of glycosaminoglycan used to construct the extracellular
      matrix, is involved in the proliferation and motility of cells, including cancer
      cells. The aim of this study was to determine whether exogenous HA has an
      influence on cancer in vitro and in vivo. High-molecular-weight HA (900 kDa) and
      low-molecular-weight HA (10 kDa) were added to several types of cancer cell lines
      in vitro, and proliferation and invasion were assessed. The effect of HA on
      capillary formation by human umbilical vein endothelial cells was also analyzed.
      The results showed that both types of HA had no apparent effect on cellular
      proliferation, invasion, or capillary formation. In an animal study, the 2 types
      of HA were orally administered to tumor-bearing mice at a dosage of 200 mg/kg/d
      for 4 wk. Analysis using an in vivo imaging system revealed that tumor
      proliferation and metastasis were not greatly altered by HA administration.
      Furthermore, CD31 immunohistochemical staining revealed no obvious change in
      tumor microvessels. Taken together, these results demonstrate that exogenously
      administered HA has little effect on cancer. This study may support the safety of
      various forms of HA administration, including oral intake. PRACTICAL APPLICATION:
      Orally administered hyaluronan was recently found to have beneficial effects.
      However, the effect of exogenous hyaluronan on cancer remains unclear. Our
      findings support the safety of orally administered hyaluronan and its use as a
      functional food ingredient.

PMID- 24894154
TI  - Thermochemistry, reaction paths, and kinetics on the tert-isooctane radical
      reaction with O2.
AB  - Thermochemical properties of tert-isooctane hydroperoxide and its radicals are
      determined by computational chemistry. Enthalpies are determined using isodesmic
      reactions with B3LYP density function and CBS QB3 methods. Application of group
      additivity with comparison to calculated values is illustrated. Entropy and heat
      capacities are determined using geometric parameters and frequencies from the
      B3LYP/6-31G(d,p) calculations for the lowest energy conformer. Internal rotor
      potentials are determined for the tert-isooctane hydroperoxide and its radicals
      in order to identify isomer energies. Recommended values derived from the most
      stable conformers of tert-isooctane hydroperoxide of are -77.85 +/- 0.44 kcal
      mol(-1). Isooctane is a highly branched molecule, and its structure has a
      significant effect on its thermochemistry and reaction barriers. Intramolecular
      interactions are shown to have a significant effect on the enthalpy of the
      isooctane parent and its radicals on peroxy/peroxide systems, the R* + O2 well
      depths and unimolecular reaction barriers. Bond dissociation energies and well
      depths, for tert-isooctane hydroperoxide -> R* + O2 are 33.5 kcal mol(-1)
      compared to values of ~38 to 40 kcal mol(-1) for the smaller tert-butyl-O2 -> R*
      + O2. Transition states and kinetic parameters for intramolecular hydrogen atom
      transfer and molecular elimination channels are characterized to evaluate
      reaction paths and kinetics. Kinetic parameters are determined versus pressure
      and temperature for the chemically activated formation and unimolecular
      dissociation of the peroxide adducts. Multifrequency quantum RRK (QRRK) analysis
      is used for k(E) with master equation analysis for falloff. The major reaction
      paths at 1000 K are formation of isooctane plus HO2 followed by cyclic ether plus
      OH. Stabilization of the tert-isooctane hydroperoxy radical becomes important at
      lower temperatures. 

PMID- 24894151
TI  - Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis
      in breast cancer cells.
AB  - BACKGROUND: Fatty acid synthase (FAS) has been proven over-expressed in human
      breast cancer cells and consequently, has been recognized as a target for breast
      cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen
      pericarp, has a variety of biological activities, including anti-cancer effect.
      In our previous study, alpha-mangostin had been found both fast-binding and slow
      binding inhibitions to FAS in vitro. This study was designed to investigate the
      activity of alpha-mangostin on intracellular FAS activity in FAS over-expressed
      human breast cancer cells, and to testify whether the anti-cancer activity of
      alpha-mangostin may be related to its inhibitory effect on FAS. METHODS: We
      evaluated the cytotoxicity of alpha-mangostin in human breast cancer MCF-7 and
      MDA-MB-231 cells. Intracellular FAS activity was measured by a spectrophotometer
      at 340 nm of NADPH absorption. Cell Counting Kit assay was used to test the cell
      viability. Immunoblot analysis was performed to detect FAS expression level,
      intracellular fatty acid accumulation and cell signaling (FAK, ERK1/2 and AKT).
      Apoptotic effects were detected by flow cytometry and immunoblot analysis of
      PARP, Bax and Bcl-2. Small interfering RNA was used to down-regulate FAS
      expression and/or activity. RESULTS: Alpha-mangostin could effectively suppress
      FAS expression and inhibit intracellular FAS activity, and result in decrease of
      intracellular fatty acid accumulation. It could also reduce cell viability,
      induce apoptosis in human breast cancer cells, increase in the levels of the PARP
      cleavage product, and attenuate the balance between anti-apoptotic and pro
      apoptotic proteins of the Bcl-2 family. Moreover, alpha-mangostin inhibited the
      phosphorylation of FAK. However, the active forms of AKT, and ERK1/2 proteins
      were not involved in the changes of FAS expression induced by alpha-mangostin.
      CONCLUSIONS: Alpha-mangostin induced breast cancer cell apoptosis by inhibiting
      FAS, which provide a basis for the development of xanthone as an agent for breast
      cancer therapy.

PMID- 24894155
TI  - The expression pattern of 19 genes predicts the histology of endometrial
      carcinoma.
AB  - Cancer diagnosis and classification have traditionally been based on the
      assessment of morphology by microscopy. However, the histological classification
      system is challenging and demand for genetic information is increasing in the era
      of targeted and personalized molecular therapy. Recently accumulated
      comprehensive genomic data could be used to provide a molecular cancer
      classification alongside the histological classification. This study identified a
      19 gene signature able to classify endometrial cancers into the two major
      histological subtypes, endometrioid and serous. In addition, when the genomic
      classifier was applied to endometrioid adenocarcinoma of high grade (EM-HG), a
      subset (23.6%, 25/106) was predicted to be similar to serous tumors at the
      molecular level. In analyses of multiple cancers, the classification model may
      also be applicable to ovarian cancers. 

PMID- 24894156
TI  - Further insights into the pharmacology of the human trace amine-associated
      receptors: discovery of novel ligands for TAAR1 by a virtual screening approach.
AB  - Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor that is
      expressed in brain and periphery and responds to a class of compounds called
      trace amines, such as beta-phenylethylamine (beta-PEA), tyramine, tryptamine,
      octopamine. The receptor is known to have a very rich pharmacology and could be
      also activated by different classes of compounds, including dopaminergic,
      adrenergic and serotonergic ligands. It is expected that targeting hTAAR1 could
      provide a novel pharmacological approach for several human disorders, such as
      schizophrenia, depression, attention deficit hyperactivity disorder, Parkinson's
      disease and metabolic diseases. Only recently, a small number of selective hTAAR1
      agonists (among which RO5166017 and T1 AM) and antagonist (EPPTB), have been
      reported in literature. With the aim to identify new molecular entities able to
      act as ligands for this target, we used an homology model for the hTAAR1 and
      performed a virtual screening procedure on an in-house database of compounds. A
      number of interesting molecules were selected and by testing them in an in vitro
      assay we found several agonists and one antagonist, with activities in the low
      micromolar range. These compounds could represent the starting point for the
      development of more potent and selective TAAR1 ligands. 

PMID- 24894157
TI  - The significance of GBA for Parkinson's disease.
AB  - From the first descriptions of Parkinson's disease (PD) and Gaucher's disease
      (GD) in the nineteenth century, it took more than 100 years to discover the link
      between the GBA gene and Parkinsonism. The observation that mutations in the GBA
      gene represent the most common genetic risk factor for PD so far only came into
      focus because of astute clinical observation of Gaucher patients and their
      families. In this review, we (i) outline how GBA was identified as a genetic risk
      factor for Parkinsonism, (ii) present clinical characteristics of GBA-associated
      Parkinsonism, (iii) discuss possible mechanisms of the underlying pathogenesis in
      GBA-associated Parkinsonism, and (iv) provide an outlook on potentially new areas
      of research and treatment that arise from this important discovery. 

PMID- 24894158
TI  - Do aphid carcasses on the backs of larvae of green lacewing work as chemical
      mimicry against aphid-tending ants?
AB  - Ants attack and exclude natural enemies of aphids in ant-aphid mutualisms.
      However, larvae of the green lacewing, Mallada desjardinsi, prey on the cowpea
      aphid, Aphis craccivora, without exclusion by aphid-tending ants. Lacewing larvae
      are protected from ants by carrying aphid carcasses on their backs. Here, we
      tested whether cuticular hydrocarbons (CHCs) of aphid carcasses affected the
      aggressiveness of aphid-tending ants. Aphid carcasses were washed with n-hexane
      to remove lipids. Lacewing larvae with washed aphid carcasses were attacked by
      aphid-tending ants more frequently than those with untreated aphid carcasses. We
      measured the aggressiveness of aphid-tending ants to lacewing larvae that were
      either carrying a piece of cotton wool (a dummy aphid carcass) treated with CHCs
      from aphids or lacewing larvae, or carrying aphid carcasses. The rates of attack
      by ants on lacewing larvae carrying CHCs of aphids or aphid carcasses were lower
      than that of attack on lacewing larvae with conspecific CHCs. Chemical analysis
      by gas chromatography/mass spectrometry showed similarity of CHCs between aphids
      and aphid carcasses. These results suggest that aphid carcasses on the backs of
      lacewing larvae function via chemical camouflage to limit attacks by aphid
      tending ants. 

PMID- 24894159
TI  - Identification and biosynthesis of novel male specific esters in the wings of the
      tropical butterfly, Bicyclus martius sanaos.
AB  - Representatives of the highly speciose tropical butterfly genus Bicyclus
      (Lepidoptera: Nymphalidae) are characterized by morphological differences in the
      male androconia, a set of scales and hair pencils located on the surface of the
      wings. These androconia are assumed to be associated with the release of
      courtship pheromones. In the present study, we report the identification and
      biosynthetic pathways of several novel esters from the wings of male B. martius
      sanaos. We found that the volatile compounds in this male butterfly were similar
      to female-produced moth sex pheromones. Components associated with the male wing
      androconial areas were identified as ethyl, isobutyl and 2-phenylethyl
      hexadecanoates and (11Z)-11-hexadecenoates, among which the latter are novel
      natural products. By topical application of deuterium-labelled fatty acid and
      amino acid precursors, we found these pheromone candidates to be produced in
      patches located on the forewings of the males. Deuterium labels from hexadecanoic
      acid were incorporated into (11Z)-11-hexadecenoic acid, providing experimental
      evidence of a Delta11-desaturase being active in butterflies. This unusual
      desaturase was found previously to be involved in the biosynthesis of female
      produced sex pheromones of moths. In the male butterflies, both hexadecanoic acid
      and (11Z)-11-hexadecenoic acid were then enzymatically esterified to form the
      ethyl, isobutyl and 2-phenylethyl esters, incorporating ethanol, isobutanol, and
      2-phenylethanol, derived from the corresponding amino acids L-alanine, L-valine,
      and L-phenylalanine. 

PMID- 24894160
TI  - Fulminant thrombotic thrombocytopenic purpura (TTP): association with amphetamine
      consumption?

PMID- 24894161
TI  - Impact of pre-operative positron emission tomography in gallbladder cancer.
AB  - BACKGROUND: Current pre-operative staging methods for gallbladder cancer (GBC)
      are suboptimal in detecting metastatic disease. Positron emission tomography
      (PET) may have a role but data are lacking. METHODS: Patients with GBC and PET
      assessed by a hepatobiliary surgeon in clinic between January 2001 and June 2013
      were retrospectively reviewed. Computed tomography (CT)/magnetic resonace imaging
      (MRI) were correlated with PET scans and analysed for evidence of metastatic or
      locally unresectable disease. Medical records were reviewed to determine if PET
      scanning was helpful by preventing non-therapeutic surgery or enabling resection
      in patients initially deemed unresectable. RESULTS: There were 100 patients
      including 63 incidental GBC. Thirty-eight patients did not proceed to surgery, 35
      were resected and 27 patients were explored but had unresectable disease. PET was
      positive for metastatic disease in 39 patients (sensitivity 56%, specificity
      94%). Five patients definitively benefitted from PET: in 3 patients PET found
      disease not seen on CT, and 2 patients with suspicious CT findings had negative
      PET and successful resections. In a further 12 patients PET confirmed equivocal
      CT findings. Three patients had additional invasive procedures performed owing to
      PET avidity in other sites. Utility of PET was higher in patients with suspicious
      nodal disease on CT [odds ratio (OR) 7.1 versus no nodal disease, P = 0.0004],
      and in patients without a prior cholecystectomy (OR 3.1 versus post
      cholecystectomy, P = 0.04). CONCLUSION: Addition of PET to conventional cross
      sectional imaging has a modest impact on management pre-operatively particularly
      in patients without a prior cholecystectomy and to confirm suspicious nodal
      disease on CT.

PMID- 24894163
TI  - Pilonidal sinus surgery: could we predict postoperative complications?
AB  - Pilonidal sinus surgery could, as of now, be considered a surgery tailored more
      to the surgeon than to the patient. In an attempt to give to surgeons an
      objective instrument of decision, we have evaluated which variables could be
      considered predictive of postoperative complications after pilonidal sinus
      surgery. A prospective electronic database of all patients treated for
      sacrococcygeal pilonidal disease was analysed. Sex, age, obesity, smoking,
      recurrent disease, the presence of multiple orifices and the distance between the
      most lateral orifice and midline were recorded and correlated with the occurrence
      of postoperative complications (infection and recurrence); 1006 patients were
      evaluated. Excision with primary mid-line closure was performed on all the
      patients. Mean follow-up was 7.3 +/- 3.6 years. A total of 158 patients with
      postoperative complications (infection and/or recurrence) were recorded during
      this period. A multivariate analysis showed that, after adjusting for major
      clinical and demographic characteristics, only a recurrent disease [odds ratio
      (OR): 3.41, 95% confidence interval (CI): 1.89-6.15, P < 0.001] and the distance
      of lateral orifice from midline (OR: 26.3, 95% CI: 12.2-56.7, P < 0.001) were
      independent predictors of overall postoperative complications. Focussing on the
      distance from midline, the receiver operative characteristic (ROC) analysis
      showed that the distance of lateral orifice from midline predicted 79.2% of
      complications and the Youden's test identified the best cut-off as 2.0 cm for
      this variable. An evidence-based tool for deciding on the type of surgical
      intervention could be developed and validated by further ad hoc prospective
      studies evaluating our results in comparison to other different types of surgical
      techniques. Our results support the use of these variables as an effective way to
      tailor pilonidal sinus surgery to the patient, so as to obtain the best results
      in patient care. 

PMID- 24894162
TI  - Methodological and ethical challenges in studying patients' perceptions of
      coercion: a systematic mixed studies review.
AB  - BACKGROUND: Despite improvements in psychiatric inpatient care, patient
      restrictions in psychiatric hospitals are still in use. Studying perceptions
      among patients who have been secluded or physically restrained during their
      hospital stay is challenging. We sought to review the methodological and ethical
      challenges in qualitative and quantitative studies aiming to describe patients'
      perceptions of coercive measures, especially seclusion and physical restraints
      during their hospital stay. METHODS: Systematic mixed studies review was the
      study method. Studies reporting patients' perceptions of coercive measures,
      especially seclusion and physical restraints during hospital stay were included.
      Methodological issues such as study design, data collection and recruitment
      process, participants, sampling, patient refusal or non-participation, and
      ethical issues such as informed consent process, and approval were synthesized
      systematically. Electronic searches of CINALH, MEDLINE, PsychINFO and The
      Cochrane Library (1976-2012) were carried out. RESULTS: Out of 846 initial
      citations, 32 studies were included, 14 qualitative and 18 quantitative studies.
      A variety of methodological approaches were used, although descriptive and
      explorative designs were used in most cases. Data were mainly collected in
      qualitative studies by interviews (n = 13) or in quantitative studies by self
      report questionnaires (n = 12). The recruitment process was explained in 59% (n =
      19) of the studies. In most cases convenience sampling was used, yet five studies
      used randomization. Patient's refusal or non-participation was reported in 37% (n
      = 11) of studies. Of all studies, 56% (n = 18) had reported undergone an ethical
      review process in an official board or committee. Respondents were informed and
      consent was requested in 69% studies (n = 22). CONCLUSIONS: The use of different
      study designs made comparison methodologically challenging. The timing of data
      collection (considering bias and confounding factors) and the reasons for non
      participation of eligible participants are likewise methodological challenges,
      e.g. recommended flow charts could aid the information. Other challenges
      identified were the recruitment of large and representative samples. Ethical
      challenges included requesting participants' informed consent and respecting
      ethical procedures.

PMID- 24894165
TI  - Hypoxia signaling and the metastatic phenotype.
AB  - Conditions of poor oxygenation (hypoxia) are present in the majority of solid
      human tumors and are associated with poor patient prognosis due to both hypoxia
      mediated resistance to treatment, and to hypoxia induced biological changes that
      promote increased malignancy, including metastasis. Tumor cells respond to
      hypoxia by activating several oxygen-sensitive signaling pathways that include
      the hypoxia inducible factor 1/2 (HIF1/2) signalling pathways and the unfolded
      protein response (UPR), which alter gene expression to promote adaptation and
      survival during hypoxic conditions. Furthermore, these hypoxia responsive
      pathways can lead to changes in gene expression and cellular phenotype that
      influence the potential of cancer cells to metastasize. However, the hypoxia
      induced signaling events that promote tumor metastasis are still relatively
      poorly understood. Previous studies have largely focused on the contribution of
      the HIF signaling pathway to hypoxia-mediated metastasis. However, recent
      evidence demonstrates that hypoxic activation of the UPR is also an important
      mediator of metastasis. 

PMID- 24894164
TI  - A genetic association study detects haplotypes associated with obstructive heart
      defects.
AB  - The development of congenital heart defects (CHDs) involves a complex interplay
      between genetic variants, epigenetic variants, and environmental exposures.
      Previous studies have suggested that susceptibility to CHDs is associated with
      maternal genotypes, fetal genotypes, and maternal-fetal genotype (MFG)
      interactions. We conducted a haplotype-based genetic association study of
      obstructive heart defects (OHDs), aiming to detect the genetic effects of 877
      SNPs involved in the homocysteine, folate, and transsulfuration pathways.
      Genotypes were available for 285 mother-offspring pairs with OHD-affected
      pregnancies and 868 mother-offspring pairs with unaffected pregnancies. A
      penalized logistic regression model was applied with an adaptive least absolute
      shrinkage and selection operator (lasso), which dissects the maternal effect,
      fetal effect, and MFG interaction effects associated with OHDs. By examining the
      association between 140 haplotype blocks, we identified 9 blocks that are
      potentially associated with OHD occurrence. Four haplotype blocks, located in
      genes MGMT, MTHFS, CBS, and DNMT3L, were statistically significant using a
      Bayesian false-discovery probability threshold of 0.8. Two blocks in MGMT and
      MTHFS appear to have significant fetal effects, while the CBS and DNMT3L genes
      may have significant MFG interaction effects. 

PMID- 24894167
TI  - Human cognitive and neuro-psychiatric bio-markers in the cardiac peri-operative
      patient.
AB  - Some of the complexities of surgical interventions include neurological and
      psychiatric disturbances. Prompt identification and early treatment of these
      complications are pivotal in achieving excellent clinical results. Recognizing
      major adverse events such as stroke, seizure or delirium is usually straight
      forward, however the discovery of less frequent or more subtle post-operative
      changes such as cognitive dysfunction might be delayed due to lack of appropriate
      diagnostic tools. This review summarizes biological markers that can be utilized
      as surrogates in evaluating surgery-related neuro-psychiatric disorders. 

PMID- 24894166
TI  - KiSS1-induced GPR54 signaling inhibits breast cancer cell migration and
      epithelial-mesenchymal transition via protein kinase D1.
AB  - The metastasis suppressor protein Kisspeptin regulates cancer cell proliferation
      and motility through its receptor, GRP54. However, the critical downstream
      effectors remain unclear. In this study, we investigated GPR54 signaling in
      breast cancer cells. Kisspeptin stimulation caused a decrease in migration of
      multiple breast cancer cell lines. Also, Kisspeptin inhibited MDA-MB-231 cell
      colony formation in 3D matrigel culture and in soft agar. Kisspeptin treatment
      elevated phosphorylated PKD1 in a PKC-dependent manner. However, knockdown of
      either GPR54 or PKD1 increased breast cancer cell migration and invasion.
      Furthermore, GPR54 knockdown blocked Kisspeptin-induced phosphorylation of PKD1.
      Finally, Kisspeptin stimulation induced a PKD1 phosphorylation-dependent decrease
      in expression of Slug, a transcription factor that drives epithelial-mesenchymal
      transition (EMT), and a concomitant increase in E-cadherin expression. Therefore,
      KiSS1/GPR54 signaling through PKD1 acts to maintain the epithelial state and to
      inhibit breast cancer cell invasiveness, and exerts functions associated with its
      role as a metastasis suppressor. 

PMID- 24894168
TI  - Reactive oxygen species: physiological roles in the regulation of vascular cells.
AB  - Reactive oxygen species (ROS) are now appreciated to play several important roles
      in a number of biological processes and regulate cell physiology and function.
      ROS are a heterogeneous chemical class that includes radicals, such as superoxide
      ion (O2(*-)), hydroxyl radical (OH(*)) and nitric oxide (NO(*)), and non
      radicals, such as hydrogen peroxide (H2O2), singlet oxygen ((1)O2), hypochlorous
      acid (HOCl), and peroxynitrite (NO3 (-)). In the cardiovascular system, besides
      playing a critical role in the development and progression of vasculopathies and
      other important pathologies such as congestive heart failure, atherosclerosis and
      thrombosis, ROS also regulate physiological processes. Evidence from a wealth of
      cardiovascular research studies suggests that ROS act as second messengers and
      play an essential role in vascular homeostasis by influencing discrete signal
      transduction pathways in various systems and cell types. They are produced
      throughout the vascular system, regulate differentiation and contractility of
      vascular smooth muscle cells, control vascular endothelial cell proliferation and
      migration, mediate platelet activation and haemostasis, and significantly
      contribute to the immune response. Our understanding of ROS chemistry and cell
      biology has evolved to the point of realizing that different ROS have distinct
      and important roles in cardiovascular physiology. This review will outline
      sources, functions and molecular mechanisms of action of different ROS in the
      cardiovascular system and will describe their emerging role in healthy
      cardiovascular physiology and homeostasis. 

PMID- 24894169
TI  - The mitochondrial thioredoxin is required for liver development in zebrafish.
AB  - Thioredoxins (Trxs) are a class of small molecular redox proteins that play an
      important role in scavenging abnormally accumulated reactive oxygen species
      (ROS). Thioredoxin 2 (Trx2) is one member of this family located in mitochondria.
      Trx2 protects cells from increased oxidative stress and has anti-apoptosis
      function. Knockout of Trx2 in mice led to early embryonic lethality. However, the
      essential role of Trx2 during embryogenesis remains unclear. To further
      investigate the role of Trx2 during embryonic development, we performed Trx2
      knockdown in zebrafish and investigated the regulation role of Trx2 during
      embryonic development. Our results indicate that Trx2 had a high expression in
      early zebrafish embryos and its knockdown in zebrafish led to defective liver
      development mainly due to increased hepatic cell death. The increased ROS and the
      imbalance of members of the Bcl-2 family were involved in cell death induced by
      Trx2 suppression in zebrafish. The dysregulation of Bax, puma and Bcl-xl promoted
      the reduction of mitochondrial trans-membrane potential and the mitochondria
      membrane permeabilization (MMP), which initiated the mitochondrial apoptosis
      pathway. Additionally, we found that the increase of relocated GAPDH in
      mitochondria may be another factor responsible for the mitochondrial catastrophe.

PMID- 24894170
TI  - Mesenchymal stem cells regulate cytoskeletal dynamics and promote cancer cell
      invasion through low dose nitric oxide.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) can be recruited to tumor
      sites and integrate into the stroma of tumors. When co-cultured with BMSCs,
      otherwise weakly metastatic nasopharyngeal carcinoma cells (NPC) showed improved
      metastatic ability. BMSCs in the tumor environment displayed the characteristics
      of macrophages. Nitric oxide produced by BMSCs in tumor environment could
      translocate caldesmon to podosome in Ca2+/calmodulin manner and promoted
      metastatic ability of NPC cells through invadopodia formation, with which the NPC
      cells degrade the extracellular matrix. Thus, we concluded that the BMSCs
      promoted cell migration and invasion through nitric oxide-induced paracrine
      signals. 

PMID- 24894171
TI  - Knockdown of H19 enhances differentiation capacity to epidermis of
      parthenogenetic embryonic stem cells.
AB  - Parthenogenetic embryonic stem (pES) cells are pluripotent stem cells derived
      from artificially activated oocytes without embryo destruction, thus eliciting
      less ethic concerns, and have been demonstrated promising for autologous stem
      cell therapy. However, pES cells could carry inappropriate imprinting such as
      relatively high expression of H19, a paternal imprinted gene, and may negatively
      influence their lineage differentiation. We show that knockdown of H19 by shRNA
      in mouse pES cells does not alter self-renewal and expression of genes associated
      with pluripotency. We find that down-regulation of H19 promotes differentiation
      of pES cells to epidermis. In addition, H19 depletion also facilitates
      differentiation of pES cells to cardiomyocytes and strong heart-like beating. Our
      data support the notion that reduction of H19 improves pES cell differentiation
      in the lineages of ectoderm and mesoderm, and provide further evidence suggesting
      that defective imprinting can be manipulated to allow potential application of
      pES cells for stem cell therapy. 

PMID- 24894172
TI  - Combination therapy with hepatocyte growth factor and oseltamivir confers
      enhanced protection against influenza viral pneumonia.
AB  - Frequent outbreaks caused by influenza viruses pose considerable public health
      threats worldwide. Virus-inflicted alveolar damage represents a major contributor
      of acute lung injury in influenza. We have previously demonstrated that
      hepatocyte growth factor (HGF) produced by macrophages enhances alveolar
      epithelial proliferation during influenza infection. Here, we investigated the
      therapeutic efficacy of recombinant human HGF (rhHGF) and an antiviral agent
      (oseltamivir) alone or in combination to treat influenza viral pneumonia in
      macrophage-depleted BALB/c mice. Combination therapy of infected mice
      significantly reduced lung pathology and mortality compared to other animal
      groups that received either treatment alone. Combination treatment with rhHGF
      induced alveolar type II (AT2) epithelial hyperplasia more prominently in the
      distal airways, evident by increased cells with double-positive staining for
      surfactant protein-C and proliferating cell nuclear antigen within the alveolar
      epithelial lining. Similarly, rhHGF supplementation also induced stem cell
      antigen-1 (SCA-1) transcriptional expression at 5 days post-infection (dpi), but
      mRNA levels of both SCA-1 and its receptor c-KIT were decreased by 10 dpi.
      Microarray and pathway analyses indicated that rhHGF administration may act by
      accelerating tissue repair and suppressing inflammatory processes to minimize
      damage by infection and to restore lung function by earlier repair. These results
      reveal that transient administration of rhHGF may confer synergistic effects in
      enhancing pulmonary repair by promoting AT2 cell proliferation. Thus, the
      combination of rhHGF and oseltamivir may represent a promising therapeutic option
      against influenza pneumonia to improve existing antiviral treatment regimens. 

PMID- 24894173
TI  - Eriocalyxin B-induced apoptosis in pancreatic adenocarcinoma cells through thiol
      containing antioxidant systems and downstream signalling pathways.
AB  - Thiol-containing antioxidant systems play an important role in regulating
      cellular redox homeostasis. Several anti-cancer agents act by targeting these
      systems by inducing the production of reactive oxygen species (ROS). Our earlier
      studies have shown that Eriocalyxin B (EriB), a diterpenoid isolated from Isodon
      eriocalyx, possesses anti-pancreatic tumour activities in vitro and in vivo. The
      present study further demonstrated that only thiol-containing antioxidants, N
      acetylcysteine (NAC) or dithiothreitol (DTT), inhibited EriB-induced cytotoxicity
      and apoptosis. EriB suppressed the glutathione and thioredoxin antioxidant
      systems, thus increasing the intracellular ROS levels and regulating the MAPK,
      NFkappaB pathways. Treatment with EriB depleted the intracellular thiol
      containing proteins in CAPAN-2 cells. In vivo studies also showed that EriB
      treatment (2.5 mg/kg) reduced the pancreatic tumour weights significantly in nude
      mice with increased superoxide levels. Taken together, our results shed important
      new light on the molecular mechanisms of EriB acting as an apoptogenic agent and
      its therapeutic potential for pancreatic cancer. 

PMID- 24894174
TI  - Galectins: major signaling modulators inside and outside the cell.
AB  - Galectins control cell behavior by acting on different signaling pathways. Most
      of the biological activities ascribed to these molecules rely upon recognition of
      extracellular glycoconjugates and establishment of multivalente interactions,
      which trigger adaptive biological responses. However, galectins are also detected
      within the cell in different compartments, where their regulatory functions still
      remain poorly understood. A deeper understanding of the entire galectin
      signalosome and its impact in cell behavior is therefore essential in order to
      delineate new strategies to specifically manipulate both galectin expression and
      function. This review summarizes our current knowledge of the signaling pathways
      activated by galectins, their glycan dependence and the cellular compartment
      where they become activated and are biologically relevant. 

PMID- 24894175
TI  - Autophagy and heart disease: implications for cardiac ischemia-reperfusion
      damage.
AB  - Survival of myocytes and mesenchymal cells in the heart is tightly regulated by a
      number of adaptive processes that are invoked with the changes that occur within
      the parenchyma and stroma. Autophagy is implicated in cellular housekeeping
      duties and maintenance of the integrity of the intracellular milieu by removal of
      protein aggregates and damaged organelles, whereas under pathophysiological
      conditions, the chronic up-regulation of autophagy may lead to significant
      disturbance of homeostatic conditions. Nonetheless, the role of autophagy in
      heart disease in the context of cardiac ischemia-reperfusion injury is currently
      unclear. This review will focus upon the role of autophagy as it pertains to
      ischemia reperfusion damage in the heart. 

PMID- 24894177
TI  - Myopathic involvement and mitochondrial pathology in Kennedy disease and in other
      motor neuron diseases.
AB  - Kennedy disease (spinal and bulbar muscular atrophy, or SBMA) is a motor neuron
      disease caused by a CAG expansion in the androgen-receptor (AR) gene. Increasing
      evidence shows that SBMA may have a primary myopathic component and that
      mitochondrial dysfunction may have some role in the pathogenesis of this disease.
      In this article, we review the role of mitochondrial dysfunction and of the
      mitochondrial genome (mtDNA) in SBMA, and we present the illustrative case of a
      patient who presented with increased CK levels and exercise intolerance.
      Molecular analysis led to definitive diagnosis of SBMA, whereas muscle biopsy
      showed a mixed myopathic and neurogenic process with "mitochondrial features" and
      multiple mtDNA deletions, supporting some role of mitochondria in the
      pathogenesis of the myopathic component of Kennedy disease. Furthermore, we
      briefly review the role of mitochondrial dysfunction in two other motor neuron
      diseases (namely spinal muscular atrophy and amyotrophic lateral sclerosis). Most
      likely, in most cases mtDNA does not play a primary role and it is involved
      subsequently. MtDNA deletions may contribute to the neurodegenerative process,
      but the exact mechanisms are still unclear. It will be important to develop a
      better understanding of the role of mitochondrial dysfunction in motoneuron
      diseases, since it may lead to the development of more effective strategies for
      the treatment of this devastating disorder. 

PMID- 24894178
TI  - Role of microRNAs in B cell leukemias and lymphomas.
AB  - MicroRNAs (miRNAs) are a class of small (18~25 nucleotides long) non-coding RNAs
      that regulate gene expression on the post-transcriptional level. During the last
      decade, the field of miRNA research has been exponentially expanding, revealing
      the widespread role of these molecules in numerous biological processes. Aberrant
      miRNA expression has been documented in multiple haematologic malignancies,
      including B cell lymphomas. There is compelling evidence that miRNAs can function
      as oncogenes or tumor suppressor genes in lymphoid malignancies. In this review,
      we recapitulate the current knowledge of miRNA expression in B cell malignancies
      and discuss the accumulating evidence for a major role of miRNA deregulation in
      the development of B cell-derived lymphoid tumors. 

PMID- 24894176
TI  - The characteristics of Bax inhibitor-1 and its related diseases.
AB  - Bax inhibitor-1 (BI-1) is an evolutionarily-conserved endoplasmic reticulum
      protein. The expression of BI-1 in mammalian cells suppresses apoptosis induced
      by Bax, a pro-apoptotic member of the Bcl-2 family. BI-1 has been shown to be
      associated with calcium (Ca(2+)) levels, reactive oxygen species (ROS)
      production, cytosolic acidification, and autophagy as well as endoplasmic
      reticulum stress signaling pathways. According to both in vitro and clinical
      studies, BI-1 promotes the characteristics of cancers. In other diseases, BI-1
      has also been shown to regulate insulin resistance, adipocyte differentiation,
      hepatic dysfunction and depression. However, the roles of BI-1 in these disease
      conditions are not fully consistent among studies. Until now, the molecular
      mechanisms of BI-1 have not directly explained with regard to how these
      conditions can be regulated. Therefore, this review investigates the
      physiological role of BI-1 through molecular mechanism studies and its
      application in various diseases. 

PMID- 24894179
TI  - Lyn regulates cytotoxicity in respiratory epithelial cells challenged by
      cigarette smoke extracts.
AB  - Cigarette smoking is associated with a series of lung diseases such as cancer,
      chronic obstructive pulmonary disease (COPD), and asthma. Despite the intense
      interest, the underlying molecular mechanism in smoking-related diseases is
      incompletely understood. Here, we show that Lyn is involved in cytotoxicity of
      respiratory epithelial cells induced by cigarette smoke extracts (CSE), an in
      vitro culture model for evaluating tobacco toxicity. In addition, exposure to CSE
      promotes the activation of JAK2 and STAT1, which is responsible for CSE-induced
      cytotoxicity. Moreover, a Lyn specific siRNA, Lyn dominant negative construct and
      pharmacological inhibitor all alleviated CSE-induced cytotoxicity in lung cells
      to different extents, respectively. Furthermore, Lyn also influences the
      phagocytosis of bacteria by murine alveolar macrophages, extending its impact on
      innate immunity. Taken together, these findings indicate that Lyn may play a role
      in the regulation of cigarette smoking-induced lung cell death, and may be a
      potential novel therapeutic target for cigarette smoking related lung diseases. 

PMID- 24894180
TI  - Machine learning-based assessment tool for imbalance and vestibular dysfunction
      with virtual reality rehabilitation system.
AB  - BACKGROUND AND OBJECTIVE: Dizziness is a major consequence of imbalance and
      vestibular dysfunction. Compared to surgery and drug treatments, balance training
      is non-invasive and more desired. However, training exercises are usually tedious
      and the assessment tool is insufficient to diagnose patient's severity rapidly.
      METHODS: An interactive virtual reality (VR) game-based rehabilitation program
      that adopted Cawthorne-Cooksey exercises, and a sensor-based measuring system
      were introduced. To verify the therapeutic effect, a clinical experiment with 48
      patients and 36 normal subjects was conducted. Quantified balance indices were
      measured and analyzed by statistical tools and a Support Vector Machine (SVM)
      classifier. RESULTS: In terms of balance indices, patients who completed the
      training process are progressed and the difference between normal subjects and
      patients is obvious. CONCLUSIONS: Further analysis by SVM classifier show that
      the accuracy of recognizing the differences between patients and normal subject
      is feasible, and these results can be used to evaluate patients' severity and
      make rapid assessment.

PMID- 24894181
TI  - Preoperative education interventions to reduce anxiety and improve recovery among
      cardiac surgery patients: a review of randomised controlled trials.
AB  - AIMS AND OBJECTIVES: To update evidence of the effectiveness of preoperative
      education among cardiac surgery patients. BACKGROUND: Patients awaiting cardiac
      surgery may experience high levels of anxiety and depression, which can adversely
      affect their existing disease and surgery and result in prolonged recovery. There
      is evidence that preoperative education interventions can lead to improved
      patient experiences and positive postoperative outcomes among a mix of general
      surgical patients. However, a previous review suggested limited evidence to
      support the positive impact of preoperative education on patients' recovery from
      cardiac surgery. DESIGN: Comprehensive review of the literature. METHODS: The
      Cochrane Central Register of Controlled Trials from the Cochrane Library,
      MEDLINE, CINAHL, PsycINFO, EMBASE and Web of Science were searched for English
      language articles published between 2000-2011. Original articles were included
      reporting randomised controlled trials of cardiac preoperative education
      interventions. RESULTS: Six trials were identified and have produced conflicting
      findings. Some trials have demonstrated the effects of preoperative education on
      improving physical and psychosocial recovery of cardiac patients, while others
      found no evidence that patients' anxiety is reduced or of any effect on pain or
      hospital stay. CONCLUSION: Evidence of the effectiveness of preoperative
      education interventions among cardiac surgery patients remains inconclusive.
      Further research is needed to evaluate cardiac preoperative education
      interventions for sustained effect and in non-Western countries. RELEVANCE TO
      CLINICAL PRACTICE: A nurse-coordinated multidisciplinary preoperative education
      approach may offer a way forward to provide a more effective and efficient
      service. Staff training in developing and delivering such interventions is a
      priority.

PMID- 24894182
TI  - Antifungal effect of Gatifloxacin and copper ions combination.
AB  - It is a well-known fact that to bring a new molecule it may take more than a
      decade. The existing drugs, which are known for their adverse reaction or
      toxicity, if utilized and allowed in different formulation, the new effective
      formulation may be discovered and developed. This may help in reducing various
      side effects, time and costs. In this study, fungal infection was inoculated
      superficially over the skin of guinea pigs and treated with the broad-spectrum
      antimicrobial (gatifloxacin) in combination with non-toxic and effective amount
      of copper ions. MIC of copper (0.20%) was also determined. Concentration of
      gatifloxacin (100 MUg ml(-1)) with the combination of copper ions (MIC) at which
      it inhibits the visible growth of fungal strains was also evaluated.
      Hematological parameters, such as total leukocyte count and differential
      leukocyte count, were evaluated. The results have shown increase in these
      parameters after fungal infection, which reaches its normal value after treatment
      with the combination of gatifloxacin and copper ions. Outcomes of the research
      concluded that gatifloxacin 100 MUg ml(-1) can be used by 0.20% of copper ions to
      prevent growth of some fungal strains (Candida albicans and Aspergillus niger),
      which causes skin infections with more potency.

PMID- 24894183
TI  - Functional and structural insights on self-assembled nanofiber-based novel
      antibacterial ointment from antimicrobial peptides, bacitracin and gramicidin S.
AB  - A novel antibacterial ointment using bacitracin, specific for Gram-positive
      bacteria, and gramicidin S, a highly toxic antibacterial peptide, was here
      developed showing broad-spectrum antibacterial activities against pathogenic
      strains with less toxicity after self-assembly into nanofiber structures. Such
      structures were confirmed with scanning electron microscopy and CD analyses. In
      addition, in silico studies using docking associated with molecular dynamics were
      carried out to obtain information about fiber structural oligomerization. Thus,
      the bacitracin and gramicidin S-based self-assembled nanopeptide ribbon may be a
      successful ointment formulation for bacterial infection control. 

PMID- 24894184
TI  - PA-1, a novel synthesized pyrrolizidine alkaloid, inhibits the growth of
      Escherichia coli and Staphylococcus aureus by damaging the cell membrane.
AB  - In the present study, antimicrobial activity and mode of a novel synthesized
      pyrrolizidine alkaloid (PA-1) were investigated. PA-1 exhibited predominantly
      strong antibacterial activity toward six bacteria tested with minimal inhibitory
      concentration (MIC) values ranging from 0.0039 to 0.025 mg ml(-1). The time-kill
      assay indicated that PA-1 killed Escherichia coli and Staphylococcus aureus
      completely at 2MIC (minimum bactericidal concentration) within 8 h. Besides, PA-1
      induced death rates of most sensitive strains (E. coli, 97.80% and S. aureus,
      96.24%) were analyzed by flow cytometry. A combination of approaches was used to
      verify the membrane damage of E. coli and S. aureus. Results showed that release
      of 260 nm absorbing materials quickly increased after PA-1 treatment. PA-1 also
      rapidly promoted the uptake of crystal violet from 24.52 to 97.12% for E. coli
      and from 19.68 to 97.63% for S. aureus when the concentrations were changed from
      MIC to 4MIC. Furthermore, the cellular membrane damages were testified by the
      significant increase of fluorescence intensity and decrease of membrane
      potential. Finally, lecithin and phosphate groups were applied to search the
      possibly targets on the cytoplasmic membrane. Results showed that PA-1 acted on
      cytoplasmic membrane phospholipids and phosphate groups of S. aureus but not of
      E. coli. In conclusion, the novel synthesized PA-1 exerted its antibacterial
      activity by acting on membrane phospholipids and phosphate groups and then
      damaging the structures of cellular membrane, which finally led to cell death. 

PMID- 24894185
TI  - Evaluation of Mycobacterium tuberculosis cross-resistance to isoniazid,
      rifampicin and levofloxacin with their respective structural analogs.
AB  - The emergence of drug-resistant, multidrug-resistant and extensively drug
      resistant tuberculosis (TB) is of major public health concern in several
      countries. In this study, the pharmacodynamic relationships among the structural
      analogs of antibiotics belonging to the same family were taken into
      consideration. The aim of this study was to compare the susceptibility of
      Mycobacterium tuberculosis to isoniazid (INH), rifampicin and levofloxacin (LX)
      to their respective structural analogs, which are frequently used as second-line
      agents. The microplate colorimetric method was used to determine the MIC to INH,
      ethionamide (ETH), rifampicin, rifabutin, LX and moxifloxacin (MOX) in clinical
      isolates previously shown to be drug resistant. Mutations conferring drug
      resistance were detected by GenoType MTBDR plus and DNA sequencing. INH and ETH
      cross-resistance was found in 95.12% (39/41) of the INH-resistant isolates
      harboring a mutation in inhAP or inhA open reading frame, but rifabutin cross
      resistance was observed in 90.0% (63/70) of the clinical isolates originally
      shown to be resistant to rifampicin. Isolates with high LX-resistance levels also
      showed high MIC to MOX. Fluoroquinolone cross-resistance was verified in isolates
      containing the gyrA94 and the gyrA90 mutation. In general, isolates with high
      INH, rifampicin and LX-resistance levels also displayed high MIC values for their
      structural analogs. These findings suggest the need to test in vitro the second
      line drugs before their incorporation in the therapeutic schemes. 

PMID- 24894186
TI  - Isolation of a novel paxilline analog pyrapaxilline from fungus that inhibits LPS
      induced NO production.
AB  - We have screened microbial culture filtrates for nitrogen monoxide (NO)
      production inhibitors using mouse macrophage cell line RAW264.7. As a result,
      paxilline, 21-isopentenylpaxilline and a novel analog of paxilline have been
      isolated from the culture filtrate of fungus Eupenicillium shearii. The novel
      analog possesses an additional dihydropyran ring, and was named as pyrapaxilline.
      This compound inhibited the NO production with lower toxicity than paxilline. 

PMID- 24894188
TI  - An outdoor radon survey and minimizing the uncertainties in low level
      measurements using CR-39 detectors.
AB  - Long term outdoor radon measurements were recorded in Ireland using CR-39 track
      etch detectors. A measurement protocol was designed for this study, which was
      optimized for the relatively low radon concentrations expected outdoors. This
      protocol included pre-etching the detectors before exposure to allow radon tracks
      to be more easily distinguished from background. The average outdoor radon
      concentration for the Republic of Ireland was found to be 5.6 +/- 0.7 Bq m(-3). A
      statistically significant difference between inland and coastal radon
      concentrations was evident but no difference between mean radon concentrations on
      the east coast and those on the west coast was observed. 

PMID- 24894189
TI  - The local structure of Pd(x)Ce(1-x)O(2-x-delta) solid solutions.
AB  - PdxCe1-xO2-x-delta solid solutions, which are highly efficient catalysts for the
      low-temperature oxidation of carbon monoxide, were examined using a set of
      structural (XRD-PDF, HRTEM, XRD) and spectral (XPS, Raman spectroscopy) methods
      in combination with quantum-chemical calculations. A comparison of the
      experimental results and pair distribution function (PDF) modeling data enabled
      reliable verification of the model of non-isomorphic substitution of Ce(4+) ions
      by Pd(2+) ions in PdxCe1-xO2-x-delta solid solutions. Palladium ions were shown
      to be in a near square planar environment with C4v symmetry, which is typical for
      Pd(2+) ions. Such a near square planar environment was revealed by Raman
      spectroscopy due to the appearance of the band at omega = 187 cm(-1), which
      corresponds to the A1 vibrational mode of Pd(2+) ions in [PdO4] subunits. The
      binding energy of Pd3d5/2 (Eb(Pd3d5/2)) for the Pd(2+) ion in the CeO2 lattice is
      1 eV higher than that of Eb(Pd3d5/2) for PdO oxide due to a decrease in the Pd-O
      distances and the formation of more ionic bonds because of the displacement of
      Pd(2+) ions with respect to the position of Ce(4+) ions in the fluorite
      structure. Five structural models of solid solutions are considered in this work.
      As demonstrated by the DFT calculations, the most realistic model is based on the
      displacement of palladium ions leading to a near square planar PdO4 environment,
      which includes water molecules stabilizing the region of anion vacancies in their
      dissociated state as two hydroxyl groups. The introduction of water molecules in
      the composition of the PdxCe1-xO2-x-delta solution leads to a decrease in the
      formation energy and to additional stabilization of palladium in the CeO2 matrix.
      The formation of PdxCe1-xO2-x-delta solid solutions is accompanied by the
      dispersing effect caused by distortions of the fluorite structure induced by
      Pd(2+) ions. The coprecipitation method, which allows Pd(2+) ions to be
      introduced at the stage of fluorite structure formation, was demonstrated to be
      the optimal method for the synthesis of a homogeneous PdxCe1-xO2-x-delta solid
      solution. 

PMID- 24894190
TI  - Is there a direct relationship between serum level of methotrexate and clinical
      efficacy and tolerability?

PMID- 24894187
TI  - Activation and measurement of NLRP3 inflammasome activity using IL-1beta in human
      monocyte-derived dendritic cells.
AB  - Inflammatory processes resulting from the secretion of Interleukin (IL)-1 family
      cytokines by immune cells lead to local or systemic inflammation, tissue
      remodeling and repair, and virologic control(1) (,) (2) . Interleukin-1beta is an
      essential element of the innate immune response and contributes to eliminate
      invading pathogens while preventing the establishment of persistent infection(1
      5). Inflammasomes are the key signaling platform for the activation of
      interleukin 1 converting enzyme (ICE or Caspase-1). The NLRP3 inflammasome
      requires at least two signals in DCs to cause IL-1beta secretion(6). Pro-IL-1beta
      protein expression is limited in resting cells; therefore a priming signal is
      required for IL-1beta transcription and protein expression. A second signal
      sensed by NLRP3 results in the formation of the multi-protein NLRP3 inflammasome.
      The ability of dendritic cells to respond to the signals required for IL-1beta
      secretion can be tested using a synthetic purine, R848, which is sensed by TLR8
      in human monocyte derived dendritic cells (moDCs) to prime cells, followed by
      activation of the NLRP3 inflammasome with the bacterial toxin and potassium
      ionophore, nigericin. Monocyte derived DCs are easily produced in culture and
      provide significantly more cells than purified human myeloid DCs. The method
      presented here differs from other inflammasome assays in that it uses in vitro
      human, instead of mouse derived, DCs thus allowing for the study of the
      inflammasome in human disease and infection.

PMID- 24894191
TI  - Response to: 'The country of residence affects the phenotype of familial
      Mediterranean fever? Is it real or a selection bias?' by Korkmaz.

PMID- 24894192
TI  - Does effort influence inequity aversion in cotton-top tamarins (Saguinus
      oedipus)?
AB  - The human sense of fairness entails sensitivity not just to equality, the equal
      division of resources, but also to merit, the relationship between an
      individual's share of resources and how hard they worked for their share. Recent
      evidence suggests that our sensitivity to equality has deep phylogenetic roots:
      several nonhuman animal species show an aversion to unequal reward distributions.
      However, the extent to which nonhuman animals share sensitivity to merit remains
      poorly understood, largely because previous studies have failed to properly
      manipulate work effort in inequity aversion tasks. Here, we tested whether cotton
      top tamarins (Saguinus oedipus) would exhibit a differential response to inequity
      when acquiring rewards was either (1) effortful or (2) effortless. Subjects
      engaged in a pulling task in which they had an opportunity to deliver a
      disadvantageously unequal distribution of food to themselves and a partner (one
      piece for self, four pieces for partner). We made delivery effortful by adding a
      weight to the pulling handle. Critically, effort was calibrated to each
      individual. Results show that individuals varied markedly in their response to
      effort, highlighting the importance of manipulating work effort at the individual
      level. Overall, subjects showed little aversion to inequity. However, subjects
      were slightly less likely to accept inequity when doing so was effortful,
      although this effect was pronounced in only one individual. Our findings suggest
      a new method for capturing individual variation in effort and for studying the
      roots of the concept of merit in nonhuman animals. 

PMID- 24894193
TI  - Administration of Lupinus albus gamma conglutin (Cgamma) to n5 STZ rats augmented
      Ins-1 gene expression and pancreatic insulin content.
AB  - Several studies support the health-promoting benefits of lupins, particularly
      lupin proteins. It has been demonstrated that Lupinus albus gamma conglutin
      (Cgamma) protein lowered blood glucose levels; thus, Cgamma showed promise as a
      new anti-diabetic compound for type 2 diabetes (T2D) treatment. The aim of this
      study was to evaluate the effect of Cgamma on Ins-1 gene expression and on
      pancreatic insulin content in streptozotocin-mediated diabetic rats. Cgamma was
      isolated from Lupinus albus seeds. Its identification was confirmed with
      polyacrylamide gel electrophoresis under native and denaturing conditions. We
      used streptozotocin (STZ) to induce T2D on the 5th day of life of newborn male
      Wistar rats (n5-STZ). After 20 weeks post-induction, these animals (glycemia >
      200 mg/dL) were randomly assigned to three groups that received the following one
      week treatments: vehicle, 0.90% w/v NaCl (n5 STZ-Ctrl); glibenclamide, 10 mg/kg
      (n5 STZ-Glib); or Cgamma, 120 mg/kg (n5 STZ-Cgamma). Glucose and insulin levels
      were measured before and after treatment. Ins-1 gene expression was quantified
      using real time polymerase chain reaction and the pancreatic insulin content was
      evaluated with immunohistochemistry. Post-treatment, the n5 STZ-Cgamma and n5 STZ
      Glib groups showed reductions in glucose, increments in serum insulin, and
      increases in Ins-1 gene expression and beta cell insulin content compared to the
      n5 STZ-Ctrl group. The results showed that Cgamma had beneficial effects on Ins-1
      gene expression and pancreatic insulin content. These biological effects of
      Cgamma strengthen its promising potential as a nutraceutical and/or new agent for
      controlling hyperglycemia.

PMID- 24894194
TI  - Rotavirus and norovirus infections among acute gastroenteritis children in
      Morocco.
AB  - BACKGROUND: Acute gastroenteritis is a serious cause of child mortality and
      morbidity in resource-limited countries. A viral etiology is most common, and
      rotavirus and norovirus are reported to be the leading causative agents. There
      are still few epidemiological data on the simultaneous occurrence of these
      viruses in Morocco. The aim of this study was to provide useful epidemiological
      data on the gastroenteritis associated with rotavirus and norovirus among
      children aged less than 5 years. METHODS: From January to December 2011, 335
      samples were tested for rotavirus and norovirus using enzyme-linked immunosorbent
      assay, reverse-transcription-polymerase chain reaction (RT-multiplex PCR) and
      real-time RT-PCR. Partial sequences of the norovirus were phylogenetically
      analyzed to determine the genotype. RESULTS: The overall rates of rotavirus and
      norovirus infections were 26.6% and 16.1%, respectively. Mixed viral infections
      were detected in 9 of 335 stool specimens (2.7%).The most common genotype
      combination in the rotavirus strains was G1[P8] (51.7%), followed by G2[P4]
      (10.1%), G2[P8] (4.5%), G9[P8] (3.4%), G4[P8] (3.4%), and G1[P6] (2.3%). Among
      patients positive for norovirus, 42 (77.8%) tested positive for GII and 12
      (22.2%) for GI. Thirty-three (78.6%) of the norovirus GII-positive cases were
      successfully characterized. Genotype GII.4 was the most prevalent (n = 27;
      81.8%), followed by GII.3 (n = 2; 6.1%), GII.13 (n = 2; 6.1%), GII.16 (n = 1;
      3%), and GII.17 (n = 1; 3%). CONCLUSION: This study suggests that in Morocco,
      norovirus is the most frequent cause of acute gastroenteritis after rotavirus,
      but further enteric viruses need to be integrated in the surveillance system so
      that a conclusion could be drawn.

PMID- 24894195
TI  - Attempted validation of the NUn score and inflammatory markers as predictors of
      esophageal anastomotic leak and major complications.
AB  - The ability to predict complications following esophagectomy/extended total
      gastrectomy would be of great clinical value. A recent study demonstrated
      significant correlations between anastomotic leak (AL) and numerical values of C
      reactive protein (CRP), white cell count (WCC) and albumin measured on
      postoperative day (POD) 4. A predictive model comprising all three (NUn score
      >10) was found to be highly sensitive and discriminant in predicting AL and
      complications. We attempted a retrospective validation in our center. Data were
      collected on all resections performed during a 5-year period (April 2008-2013)
      using prospectively maintained databases. Our biochemistry laboratory uses a
      maximum CRP value (156 mg/L), unlike that of the original study; otherwise all
      variables and outcome measures were comparable. Analysis was performed for all
      patients with complete blood results on POD4. Three hundred twenty-six patients
      underwent resection, of which 248 had POD4 bloods. There were 21 AL overall
      (6.44%); 16 among those with complete POD4 blood results (6.45%). There were 8
      (2.45%) in-hospital deaths; 7 (2.82%) in those with POD4 results. No parameters
      were associated with AL or complication severity on univariate analysis. WCC was
      associated with AL in multivariate binary logistic regression with albumin and
      CRP (OR 1.23 [95% CI 1.03-1.47]; P = 0.021). When a binary variable of CRP >= 156
      mg/L was used rather than an absolute value, no factors were significant. Mean
      NUn was 8.30 for AL, compared with 8.40 for non-AL (P = 0.710 independent t
      test). NUn > 10 predicted 0 of 16 leaks (sensitivity 0.00%, specificity 94.4%,
      receiver operator curve [ROC] area under the curve [AUC] 0.485; P = 0.843). NUn >
      7.65 was 93% sensitive and 21.6% specific. ROC for WCC alone was comparable with
      NUn (AUC 0.641 [0.504-0.779]; P = 0.059; WCC > 6.89 93.8% sensitive, 20.7%
      specific; WCC > 15 6.3% sensitive and 97% specific). There were no associations
      between any parameters and other complications. In a comparable cohort with the
      original study, we demonstrated a similar multivariate association between WCC
      alone on POD4 and subsequent demonstration of AL, but not albumin or CRP
      (measured up to 156 mg/L). The NUn score overall (calculated with this caveat)
      and a threshold of 10 was not found to have clinical utility in predicting AL or
      complications.

PMID- 24894196
TI  - Breast cancer cell apoptosis with phytoestrogens is dependent on an estrogen
      deprived state.
AB  - Phytoestrogens have been investigated as natural alternatives to hormone
      replacement therapy and their potential as chemopreventive agents. We
      investigated the effects of equol, genistein, and coumestrol on cell growth in
      fully estrogenized MCF7 cells, simulating the perimenopausal state, and long-term
      estrogen-deprived MCF7:5C cells, which simulate the postmenopausal state of a
      woman after years of estrogen deprivation, and compared the effects with that of
      steroidal estrogens: 17beta estradiol (E2) and equilin present in conjugated
      equine estrogen. Steroidal and phytoestrogens induce proliferation of MCF7 cells
      at physiologic concentrations but inhibit the growth and induce apoptosis of
      MCF7:5C cells. Although steroidal and phytoestrogens induce estrogen-responsive
      genes, their antiproliferative and apoptotic effects are mediated through the
      estrogen receptor. Knockdown of ERalpha using siRNA blocks all estrogen-induced
      apoptosis and growth inhibition. Phytoestrogens induce endoplasmic reticulum
      stress and inflammatory response stress-related genes in a comparable manner as
      the steroidal estrogens. Inhibition of inflammation using dexamethasone blocked
      both steroidal- and phytoestrogen-induced apoptosis and growth inhibition as well
      as their ability to induce apoptotic genes. Together, this suggests that
      phytoestrogens can potentially be used as chemopreventive agents in older
      postmenopausal women but caution should be exercised when used in conjunction
      with steroidal anti-inflammatory agents due to their antiapoptotic effects.

PMID- 24894199
TI  - Learning from Semmelweis: engaging in sensible infection control.

PMID- 24894198
TI  - Dihydromyricetin activates AMP-activated protein kinase and P38(MAPK) exerting
      antitumor potential in osteosarcoma.
AB  - Numerous patients with osteosarcoma either are not sensitive to chemotherapy or
      develop drug resistance to current chemotherapy regimens. Therefore, it is
      necessary to develop several potentially useful therapeutic agents.
      Dihydromyricetin is the major flavonoid component derived from Ampelopsis
      grossedentata, which has a long history of use in food and medicine. The present
      study examined the antitumor activity both in vitro and in vivo without
      noticeable side effects and the underlying mechanism of action of
      dihydromyricetin in osteosarcoma cells. We found that dihydromyricetin induced
      increased p21 expression and G2-M cell-cycle arrest, caused DNA damage, activated
      ATM-CHK2-H2AX signaling pathways, and induced apoptosis in osteosarcoma cells as
      well as decreasing the sphere formation capability by downregulating Sox2
      expression. Mechanistic analysis showed that the antitumor potential of
      dihydromyricetin may be due to the activation of AMPKalpha and p38(MAPK), as the
      activating AMPKalpha led to the inactivation of GSK3beta in osteosarcoma cells.
      Moreover, GSK3beta deletion or GSK3beta inhibition by LiCl treatment resulted in
      increased p21 expression and reduced Sox2 expression in osteosarcoma cells. Taken
      together, our results strongly indicate that the antitumor potential of
      dihydromyricetin is correlated with P38(MAPK) and the AMPKalpha-GSK3beta-Sox2
      signaling pathway. Finally, immunohistochemical analysis indicated that some
      patients had a lower p-AMPK expression after chemotherapy, which supports that
      the combination of dihydromyricetin and chemotherapy drug will be beneficial for
      patients with osteosarcoma. In conclusion, our results are the first to suggest
      that dihydromyricetin may be a therapeutic candidate for the treatment of
      osteosarcoma.

PMID- 24894197
TI  - A functional variant in NKX3.1 associated with prostate cancer risk in the
      Selenium and Vitamin E Cancer Prevention Trial (SELECT).
AB  - NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously
      found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knockout
      mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1
      activity modifies the effect of antioxidant administration on prostate
      carcinogenesis. Interestingly, administration of the antioxidant vitamin E
      significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer
      Prevention Trial (SELECT), suggesting that our animal experiments may be relevant
      to humans. To determine whether NKX3.1 played a role in increased human prostate
      cancer risk associated with antioxidant administration in SELECT, we investigated
      the joint risk of antioxidant administration and NKX3.1 genotypes previously
      found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA
      binding activity in vitro (rs2228013) in the SELECT biomarker case-cohort
      substudy (1,866 cases; 3,135 non-cases). Multivariable COX regression models were
      developed to determine the joint association of NKX3.1 genotypes with
      administration of vitamin E, selenium, or the combination, compared with placebo.
      The CC genotype at rs11781886 combined with selenium administration was
      associated with increased overall prostate cancer risk [HR, 1.676; 95% confidence
      interval (CI), 1.011-2.777; P = 0.045] and low-grade prostate cancer risk (HR,
      1.811; 95% CI, 1.016-3.228; P = 0.0441). Similarly, the rs11781886 minor allele
      (CC+CT) combined with vitamin E administration was significantly associated with
      increased prostate cancer risk (HR, 1.450; 95% CI, 1.117-1.882; P = 0.0052). Our
      results indicate that variation in NKX3.1 expression combined with selenium or
      vitamin E treatment modifies the risk of prostate cancer. Genetic background may
      modulate the effects of antioxidant supplementation thought to act as
      chemoprevention agents.

PMID- 24894200
TI  - Maternal stress associated with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To assess parental stress levels of mothers of children with juvenile
      idiopathic arthritis (JIA) aged between 2-12 years and compare with those
      reported for other chronic childhood illnesses. METHODOLOGY: Mothers of children
      aged between 2-12 years with JIA were recruited from hospital-based outpatient
      clinics. Maternal stress was measured by using the Parenting Stress Index Long
      Form (PSI). The physician assessing the child completed an active joint count, a
      physician's global assessment and recorded the C-reactive protein and/or
      erythrocyte sedimentation rate if one was clinically indicated. RESULTS: The
      mothers recruited had children with a mean age of 6 years. The mean total stress
      score of mothers of children with JIA measured by the PSI was 235.4 (95% CI 218.5
      252.3) was greater than the mean total stress scores for mothers of normal
      children at 222.8 (95% CI 221.4-224.2). It was also greater than children with
      other chronic disorders such as insulin-dependent diabetes mellitus (IDDM), 218.1
      (95% CI 204.7-231.6) and profound deafness, 221.7 (95% CI 206.4-237.0). One third
      of mothers had total PSI scores that were in the clinical range (Total PSI >
      260), indicating a need for intervention. CONCLUSION: JIA should be regarded as a
      significant illness in which maternal stress is at least equivalent to that
      associated with the care of children with other chronic diseases of childhood.

PMID- 24894201
TI  - Understanding and treating vaginismus: a multimodal approach.
AB  - INTRODUCTION AND HYPOTHESIS: This clinical opinion was written to bring attention
      to the understanding and treatment of vaginismus, a condition that is often under
      diagnosed and therefore inadequately treated, yet affects millions of women
      worldwide. Despite its description more than a century ago, vaginismus is rarely
      taught in medical school, residency training, and medical meetings. The DSM 5
      classification stresses that vaginismus is a penetration disorder in that any
      form of vaginal penetration such as tampons, finger, vaginal dilators,
      gynecological examinations, and intercourse is often painful or impossible.
      Compared with other sexual pain disorders such as vulvodynia and vestibulodynia,
      the treatment of vaginismus has the potential for a high rate of success.
      Stratifying the severity of vaginismus allows the clinician to choose among
      numerous treatment options and to better understand what the patient is
      experiencing. Vaginismus is both a physical and an emotional disorder. In the
      more severe cases of vaginismus women (and men) complain that attempted
      intercourse is like "hitting a wall" suggestive of spasm at the level of the
      introitus. The emotional fallout resulting from this needs to be addressed in any
      form of treatment applied. METHODS: This article is based on lessons learned in
      the treatment of more than 250 patients and evaluation of more than 400
      inquiries, and was written to make vaginismus more widely understood, to aid in
      the differential diagnosis of sexual pain, suggest a variety of effective
      treatments, and explain how Botox can be used as part of a multimodal treatment
      program to treat vaginismus. CONCLUSIONS: With greater awareness among clinicians
      it is hoped that medical schools, residency programs, and medical meetings will
      begin teaching the understanding and treatment of vaginismus.

PMID- 24894202
TI  - A prospective study of a single-incision sling at the time of robotic
      sacrocolpopexy.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to evaluate the
      efficacy and safety of the Miniarc Precise(r) single-incision sling (American
      Medical Systems, Minnetonka, MN, USA) placed at the time of a robotic
      sacrocolpopexy. METHODS: This was a prospective study of a single-incision
      suburethral sling placed at the time of robotic sacrocolpopexy in women with
      stress urinary incontinence (SUI) and pelvic organ prolapse. Primary outcome
      measure was cure at 1 year, defined objectively by a negative cough stress test
      (CST) and subjectively by a score of "0 or 1" on question 17 of the Pelvic Floor
      Distress Inventory (PFDI-20): "Do you experience urine leakage related to
      coughing/sneezing/laughing?" Secondary outcome measures included the change in
      Urinary Distress Inventory (UDI-6) and Urinary Impact Questionnaire (UIQ-7)
      scores at 1 year. All sling-related complications were reported. Paired Student's
      t test and the Wilcoxon signed-rank test were used for statistical analysis.
      RESULTS: One hundred and one patients were included between August 2010 and July
      2012. One-year follow-up was available for 97 out of 101 patients (96 %).
      Objective cure was 90 % and subjective cure was 87 %. Baseline UDI-6 scores
      improved from 34.8 +/- 25.1 to 6.7 +/- 11.2 at 1 year (p < 0.001). Similarly, UIQ
      7 scores improved from 21.1 +/- 22.8 to 2.4 +/- 8.2 at 1 year (p < 0.001). There
      were no intraoperative cystotomies, no mesh erosions, no sling revisions, and no
      cases of urinary retention. The retreatment rate for persistent SUI was 8 % (8
      out of 97). CONCLUSIONS: The addition of a single-incision suburethral sling at
      the time of robotic sacrocolpopexy in women with SUI resulted in an 87 % cure
      rate at 1 year.

PMID- 24894203
TI  - Laparoscopic sacrocolpopexy with deep attachment of anterior and posterior mesh.
AB  - INTRODUCTION: Sacrocolpopexy is considered a gold standard to cure apical
      prolapse, and since the US Food and Drug Administration (FDA) warning about
      complications of vaginal mesh surgery, the technique is increasingly used.
      Surgeons perform sacrocolpopexy in different variations, some by attaching the
      mesh to the apical third of the vagina, and others by applying the mesh
      anteriorly to the level of the bladder neck and posteriorly to the inner part of
      the perineum. The different techniques are neither standardized nor evaluated by
      randomized controlled trials. METHODS: This video aims to provide insight into
      the technique of deep placement of anterior and posterior mesh. CONCLUSIONS: The
      video shows that deep mesh placement is feasible and can be performed with
      standardized parameters. The technique is based on 12 years of experience with
      laparoscopic sacrocolpopexy; 1- and 5-year results, published in this journal,
      show it is safe and provides good long-term results.

PMID- 24894204
TI  - Enantioselectively-catalyzed reactions with (E)-2-alkenoyl-pyridines, their N
      oxides, and the corresponding chalcones.

PMID- 24894205
TI  - Xenotransplantation literature update, March-April 2014.

PMID- 24894207
TI  - Ministers need to heed nurses' message on pay.
AB  - Nurses, midwives and healthcare assistants will join NHS colleagues in England in
      protests this week at the government's decision not to award a cost-of-living pay
      rise this year. Thousands are expected to turn out at venues across the country
      on Thursday, when all the unions representing health service workers will join
      forces. 

PMID- 24894208
TI  - Nurses demand significant changes to revised NMC code of conduct.
AB  - The Nursing and Midwifery Council's revised code of conduct is so long and
      detailed it will be impossible to use. 

PMID- 24894212
TI  - Private healthcare provider to pilot apprenticeship as a way into nursing.
AB  - Applications are open for one of a new wave of apprenticeship courses to help
      healthcare assistants and school leavers move into nursing. 

PMID- 24894210
TI  - Work-based degree for older people specialists.
AB  - A work-based degree course in older people's care has been established at the
      University of Surrey. Subjects will include dementia and end of life care. 

PMID- 24894213
TI  - Bus stop mural a hit with patients and staff.
AB  - Patients with dementia and nurses at Warrington Hospital in Cheshire can share a
      chat while sitting in front of a mocked-up bus stop - one of the design features
      included in a L1 million ward redesign to provide relaxation and stimulation for
      patients. 

PMID- 24894214
TI  - Lack of hospital handover is making our jobs harder, say district nurses.
AB  - Poor communication between community nurses and their hospital counterparts is
      contributing to low morale and poor job satisfaction among district nurses. 

PMID- 24894206
TI  - Viral and cellular factors underlying neuropathogenesis in HIV associated
      neurocognitive disorders (HAND).
AB  - As the HIV-1 epidemic enters its fourth decade, HIV-1 associated neurological
      disorders (HAND) continue to be a major concern in the infected population,
      despite the widespread use of anti-retroviral therapy. Advancing age and
      increased life expectancy of the HIV-1 infected population have been shown to
      increase the risk of cognitive dysfunction. Over the past 10 years, there has
      been a significant progress in our understanding of the mechanisms and the risk
      factors involved in the development of HAND. Key events that lead up to neuronal
      damage in HIV-1 infected individuals can be categorized based on the interaction
      of HIV-1 with the various cell types, including but not limited to macrophages,
      brain endothelial cells, microglia, astrocytes and the neurons. This review
      attempts to decipher these interactions, beginning with HIV-1 infection of
      macrophages and ultimately resulting in the release of neurotoxic viral and host
      products. These include: interaction with endothelial cells, resulting in the
      impairment of the blood brain barrier; interaction with the astrocytes, leading
      to metabolic and neurotransmitter imbalance; interactions with resident immune
      cells in the brain, leading to release of toxic cytokines and chemokines. We also
      review the mechanisms underlying neuronal damage caused by the factors mentioned
      above. We have attempted to bring together recent findings in these areas to help
      appreciate the viral and host factors that bring about neurological dysfunction.
      In addition, we review host factors and viral genotypic differences that affect
      phenotypic pathological outcomes, as well as recent advances in treatment options
      to specifically address the neurotoxic mechanisms in play. 

PMID- 24894216
TI  - Prison term for nurse who exposed child to HIV risk.
AB  - Nursing leaders have expressed dismay over the imprisonment of an HIV-positive
      nurse found guilty in Uganda of criminal negligence for placing a patient at risk
      of infection. 

PMID- 24894217
TI  - Call for training to fight obesity.
AB  - Small amounts of weight loss maintained over a lifetime can have long-term health
      benefits. 

PMID- 24894218
TI  - Nutritional care guides aim to combat risk of malnourishment.
AB  - Nurses have a pivotal role to play in fighting malnutrition, which is costing the
      NHS billions of pounds every year, a leading nurse said. 

PMID- 24894219
TI  - Screening for genetic cholesterol risk begins.
AB  - Specialist nurses in England and Scotland will begin a genetic testing programme
      to identity people with inherited risk of potentially fatal cholesterol levels. 

PMID- 24894221
TI  - NHS should back local hospitals, says new chief executive.
AB  - The NHS should follow other western European countries and treat more patients in
      smaller local hospitals, says its new chief executive Simon Stevens. 

PMID- 24894220
TI  - Chief nurse urges trusts to fill vacancies with permanent staff.
AB  - Northern Ireland's chief nurse has written to the chief executives of the
      country's five health and social care trusts telling them to create 'permanent
      posts' where there has been persistent use of bank and agency staff. 

PMID- 24894222
TI  - Staffing data will include agency nurses so permanent shortages will be masked.
AB  - Agency nurses will be counted towards overall nurse numbers as employers prepare
      to go public with their staffing levels, it has emerged. 

PMID- 24894225
TI  - 'The new system will differ from PREP - it will be fit for purpose'.
AB  - Nurses and midwives across the UK are being urged to take part in the Nursing and
      Midwifery Council's consultation on a revised Code, which sets out the standards,
      performance and ethics registrants will be expected to adhere to when it is
      introduced later this year. 

PMID- 24894231
TI  - Infertility.

PMID- 24894232
TI  - Matter of life or death.

PMID- 24894233
TI  - The challenge of going smoke-free.
AB  - It is hard not to think about smoking when you go to many hospitals today, either
      as a patient, visitor or member of staff. Chances are that the entrance to the
      grounds, and certainly to the hospital itself, will have prominent signage
      warning people that they are entering a smoke-free zone.

PMID- 24894246
TI  - OvuView: ovulation and fertility app.

PMID- 24894248
TI  - We need a career ladder that joins academia to hands-on nursing care.
AB  - Stephen Wright (Analysis May 21) talks of a credibility gap between the UK's 262
      nursing professors and 1,308 medical professors. 

PMID- 24894249
TI  - Recruiting the right people is key to avoiding care home cruelty.

PMID- 24894250
TI  - Directors need vision to combine academic and clinical roles.

PMID- 24894251
TI  - Forget the cultural niceties, we need to see FGM as child abuse.

PMID- 24894253
TI  - The NHS displays absurd double standards on circumcision.

PMID- 24894254
TI  - Communicating with older ethnic minority patients.
AB  - In a time of increasing cultural diversity, it is essential that healthcare
      professionals respond by providing culturally competent care. Healthcare
      professionals must recognise the diverse needs of people from ethnic minority
      communities to ensure that they receive equal standards of care. This is
      particularly pertinent when providing care for older ethnic minority patients who
      may not be fluent in English. This article focuses on the need to communicate
      effectively with this group of patients to meet their health and social care
      needs, with the ultimate aim of improving patient outcomes. 

PMID- 24894255
TI  - Transcutaneous electrical nerve stimulation: review of effectiveness.
AB  - The effectiveness of transcutaneous electrical nerve stimulation (TENS) for pain
      relief has been challenged. This article evaluates systematic review findings and
      demonstrates that studies using appropriate TENS technique and dosage are more
      likely to demonstrate clinical efficacy. Therefore, it seems reasonable to
      continue to use TENS as a pain management intervention. 

PMID- 24894256
TI  - Rabies: prevention strategies for overseas travellers.
AB  - Rabies is a fatal viral disease that causes acute inflammation of the brain in
      humans. Transmission is usually through a bite or scratch or contact with the
      saliva of an infected animal. However, it is a vaccine preventable disease. It is
      important that those travelling to rabies-endemic countries are aware of the risk
      of rabies transmission and the role of pre and post-exposure vaccination. 

PMID- 24894257
TI  - Blood glucose monitoring.
AB  - I found the CPD article on blood glucose monitoring and management in acute
      stroke care interesting and informative. As I am a mental health nursing student,
      my knowledge of chronic physical conditions is limited, so I learned a lot. 

PMID- 24894258
TI  - Growth opportunity.
AB  - As a career development opportunity, RCN congress is unparalleled. Debates,
      fringe meetings, seminars, start-up events for new specialties and interest
      groups, product launches and networking opportunities for nurses to learn about
      developments in other workplaces all take place against a backdrop of one of the
      largest exhibitions at any conference. 

PMID- 24894259
TI  - 'Navy assignments test me to the limit'.
AB  - I am a specialist intensive care nurse, a specialist neurological trauma nurse
      and I have just completed my MSc in advanced practice neuroscience care. 

PMID- 24894262
TI  - Student life - Searching for the evidence.
AB  - Searching, reviewing and appraising published research evidence is a fundamental
      skill of the graduate nurse and a cornerstone of evidence-based nursing practice.
      Honours degree students demonstrate competence in this skill in their final-year
      dissertations. 

PMID- 24894264
TI  - Invoking the muse: Dada's chaos.
AB  - Dada, a self-proclaimed (anti)art (non)movement, took shape in 1916 among a group
      of writers and artists who rejected the traditions of a stagnating bourgeoisie.
      Instead, they adopted means of creative expression that embraced chaos, stoked
      instability and undermined logic, an outburst that overturned centuries of
      classical and Romantic aesthetics. Paradoxically, this insistence on disorder
      foreshadowed a new order in understanding creativity. Nearly one hundred years
      later, Nonlinear Dynamical Systems theory (NDS) gives renewed currency to Dada's
      visionary perspective on chance, chaos and creative cognition. This paper
      explores commonalities between NDS-theory and this early precursor of the
      nonlinear paradigm, suggesting that their conceptual synergy illuminates what it
      means to 'be creative' beyond the disciplinary boundaries of either. Key features
      are discussed within a 5P model of creativity based on Rhodes' 4P framework
      (Person, Process, Press, Product), to which I add Participant-Viewer for the
      interactivity of observer-observed. Grounded in my own art practice, several
      techniques are then put forward as non-methodical methods that invoke creative
      border zones, those regions where Dada's chance and design are wedded in a
      dialectical tension of opposites. 

PMID- 24894263
TI  - Can surface EMG be adequately described by digital sampling?
AB  - Surface electromyography (SEMG) is a common tool to evaluate muscle function in
      kinesiological studies, musculoskeletal rehabilitation, prosthetics, clinical
      research and neurological disease diagnosis. The acquisition of SEMG is a
      crucially basic issue to gain an insight into musculoskeletal system function.
      The aim of this study is to investigate if the sampled surface EMG signals can
      reflect adequately the neural activity of the underlying musculature. The surface
      EMG signals of four muscles (abductor pollicis muscles and abductor digiti minimi
      muscles of right hand and left hand) are studied on the amplitude, frequency and
      nonlinear measure based on symplectic geometry. There are obvious differences in
      nonlinear measures of the different sampled signals, although there are little
      significant changes in their amplitude and frequency measures. Meanwhile, surface
      EMG signals obviously differ from their surrogate data at higher sampling
      frequencies. The results indicate that surface EMG signals contain nonlinear
      components. To gather the sufficient information of surface EMG signal, the data
      acquisition should be required at the higher sampling frequency. Furthermore, the
      nonlinear measure based on symplectic geometry can be used as a sensitive index
      for evaluation of the activity of the human muscles. 

PMID- 24894265
TI  - Collaborative play in young children as a complex dynamic system: revealing
      gender related differences.
AB  - This study was focused on the role of gender-related differences in collaborative
      play, by examining properties of play as a complex system, and by using micro
      genetic analysis techniques. A complex dynamic systems model of dyadic play was
      used to make predictions with regard to duration and number of contact-episodes
      during play of same-sex dyads, both on the micro- (i.e., per individual session),
      meso- (i.e., in smoothed data), and macro time scale (i.e., the change over six
      consecutive play sessions). The empirical data came from a study that examined
      the collaborative play skills of children who experienced six twenty minute play
      sessions within a three week period of time. Monte Carlo permutation analyses
      were used to compare model predictions and empirical data. The findings point to
      strongly asymmetric distributions in the duration and number of contact episodes
      in all dyads over the six sessions, as a direct consequence of the underlying
      dynamics of the play system. The model prediction that girls-dyads would show
      longer contact episodes than boys-dyads was confirmed, but the prediction
      regarding the difference in number of peaks was not confirmed. In addition, the
      majority of the model predictions regarding changes over the course of six
      sessions were consistent with the data. That is, the average duration and the
      maximum duration of contact-episodes increases both in boys-dyads and girls
      dyads, but differences occur in the strength of the increase. Contrary to
      expectation, the number of contact-episodes decreases both in boys-dyads and in
      girls-dyads. 

PMID- 24894267
TI  - The performance-variability paradox, financial decision making, and the curious
      case of negative Hurst exponents.
AB  - This study examined the relationship between performance variability and actual
      performance of financial decision makers who were working under experimental
      conditions of increasing workload and fatigue. The rescaled range statistic, also
      known as the Hurst exponent (H) was used as an index of variability. Although H
      is defined as having a range between 0 and 1, 45% of the 172 time series
      generated by undergraduates were negative. Participants in the study chose the
      optimum investment out of sets of 3 to 5 options that were presented a series of
      350 displays. The sets of options varied in both the complexity of the options
      and number of options under simultaneous consideration. One experimental
      condition required participants to make their choices within 15 sec, and the
      other condition required them to choose within 7.5 sec. Results showed that (a)
      negative H was possible and not a result of psychometric error; (b) negative H
      was associated with negative autocorrelations in a time series. (c) H was the
      best predictor of performance of the variables studied; (d) three other
      significant predictors were scores on an anagrams test and ratings of physical
      demands and performance demands; (e) persistence as evidenced by the
      autocorrelations was associated with ratings of greater time pressure. It was
      concluded, furthermore, that persistence and overall performance were correlated,
      that 'healthy' variability only exists within a limited range, and other
      individual differences related to ability and resistance to stress or fatigue are
      also involved in the prediction of performance. 

PMID- 24894266
TI  - The role of self-injury in behavioral flexibility and resilience.
AB  - Severe and persistent self-injurious behavior (SIB) is notoriously difficult to
      understand and to treat. The current study used self-organization theory to
      investigate the possible relationship between SIB and changing levels of
      behavioral flexibility. Data consisted of categorical time-series of sequential
      behaviors from individuals with developmental disabilities and severe SIB.
      Orbital Decomposition was used to analyze each series for measures of structure
      and entropy. Overall, results showed evidence for self-organization in behavior
      patterns. Second, series including SIB were on average more flexible than those
      without SIB; while, higher numbers of SIB events (perseveration) were associated
      with higher behavioral rigidity and structural disintegration. Finally, there was
      evidence that behavioral flexibility almost always shifts reliably after a
      discrete bout of SIB, either increasing or decreasing in complexity. Altogether,
      these results may provide a deeper and more theoretically grounded understanding
      of the function of SIB beyond the traditional behavioral paradigm involving
      simple stimulus-response or response-consequence relations. Instead, some
      behaviors, such as SIB, may serve a resilience-making function as more global
      regulators of behavioral flexibility and coherence. 

PMID- 24894268
TI  - Image-guided convection-enhanced delivery into agarose gel models of the brain.
AB  - Convection-enhanced delivery (CED) has been proposed as a treatment option for a
      wide range of neurological diseases. Neuroinfusion catheter CED allows for
      positive pressure bulk flow to deliver greater quantities of therapeutics to an
      intracranial target than traditional drug delivery methods. The clinical utility
      of real time MRI guided CED (rCED) lies in the ability to accurately target,
      monitor therapy, and identify complications. With training, rCED is efficient and
      complications may be minimized. The agarose gel model of the brain provides an
      accessible tool for CED testing, research, and training. Simulated brain rCED
      allows practice of the mock surgery while also providing visual feedback of the
      infusion. Analysis of infusion allows for calculation of the distribution
      fraction (Vd/Vi) allowing the trainee to verify the similarity of the model as
      compared to human brain tissue. This article describes our agarose gel brain
      phantom and outlines important metrics during a CED infusion and analysis
      protocols while addressing common pitfalls faced during CED infusion for the
      treatment of neurological disease. 

PMID- 24894269
TI  - Large bilateral tubercular pyosalpinx in a young woman with genitourinary
      malformation: a case report.
AB  - INTRODUCTION: Tuberculosis is a chronic infectious disease, and the morbidity
      associated with it has major health implications. When tuberculosis affects the
      genital organs of young females, it has the devastating effect of causing
      irreversible damage to their fallopian tubes, resulting in a possible tubercular
      pyosalpinx and infertility. However, the disease often remains silent or presents
      with very few specific symptoms. In adolescents and young women, tuberculosis can
      also present with hypogastric recurrent symptoms and affectation of the general
      state, but because in our country genital tuberculosis is uncommon, its diagnosis
      is unlikely. CASE PRESENTATION: We describe the case of an 18-year-old Spanish
      woman who had been sexually active for 1 year, nulliparous, who presented with
      hypogastric discomfort and repeated urinary symptoms complicated with pelvic
      inflammatory disease after a hysterosalpingography. Genital tuberculosis was not
      suspected. The echographical findings and tumor markers mimicked those of ovarian
      tumors, and she was also a carrier of a genitourinary malformation (pelvic kidney
      and septate uterus). A laparotomy was performed and revealed large pelvic
      abscesses. On her right adnexum, the large pyosalpinx was free (floating
      pyosalpinx). Drainage, adhesiolysis and bilateral salpingectomy were performed,
      and cultures were taken. Histopathological study showed bilateral granulomatous
      abscessificated salpingitis with suspicion of genital tuberculosis, and cultures
      were positive for Mycobacterium tuberculosis. She followed a tuberculostatic
      treatment for 6 months. Eight years later, she presents with normal menstruations
      and is waiting for an in vitro fertilization cycle. CONCLUSIONS: No other
      reported case showing similar association of genital tuberculosis and
      genitourinary malformation was found. The associated genitourinary malformation
      in this case probably has no relation but it could contribute to diagnosis delay
      and/or to reactivate the pathology. The hysterosalpingographical findings and the
      observation of a floating pyosalpinx must alert the clinician to genital
      tuberculosis, but the diagnosis is suggested by the histopathological studies and
      confirmed by cultures. In this case study, the necessity of considering the risk
      of pelvic inflammatory disease reactivation after hysterosalpingography, of
      suspecting the diagnosis of genital tuberculosis and of establishing the
      differential diagnosis with ovarian tumors in the presence of large pyosalpinges
      is highlighted.

PMID- 24894272
TI  - Why patients should be heeded.

PMID- 24894270
TI  - The antihypercholesterolemic effect of jatrorrhizine isolated from Rhizoma
      Coptidis.
AB  - Current work was conducted to evaluate the safety and antihypercholesterolemic
      activity of jatrorrhizine extracted from Rhizoma Coptidis (RC) and its potential
      mechanism on regulating cholesterol metabolism. It was found that the LD50 of
      jatrorrhizine in mice was more than 5,500 mg/kg and there were no influences on
      clinical signs, organ weight changes, urinalysis and hematological parameters,
      gross necropsy and histological alterations in jatrorrhizine-treated rats during
      the 3-month period, compared to the control group. Jatrorrhizine showed a strong
      lipid-lowering effect in a dose-dependent manner. Oral administration of 70.05
      mg/kg of jatrorrhizine on Mesocricetus auratus (Syrian golden hamsters) exhibited
      significant decrease in TC, TG, and LDL-c levels by 20%, 43%, and 19%,
      respectively, and increase in HDL-c and total bile acids (TBA) content in feces
      (p<0.01), compared to high-fat and high-cholesterol (HFHC) group. Besides,
      jatrorrhizine dose-dependently slowed the rate of weight gain. The results of qRT
      PCR, western blotting and ELISA revealed that jatrorrhizine significantly up
      regulated the mRNA and protein expression of LDLR and CYP7A1, but exhibited no
      significant effect on mRNA and protein expression of HMGR and ASBT in hamsters.
      In conclusion, jatrorrhizine was a safe and potential antihypercholesterolemic
      agent from RC which could improve the utilization and excretion of cholesterol by
      up-regulating the mRNA and protein expression of LDLR and CYP7A1.

PMID- 24894273
TI  - Revalidation may have hidden cost as staff need training.

PMID- 24894271
TI  - Evidence-based management of necrotizing pancreatitis.
AB  - OPINION STATEMENT: Pancreatic necrosis may result as a complication of acute
      pancreatitis, often causing significant morbidity and mortality. There are many
      recommendations concerning the management of pancreatic necrosis, including non
      operative management with supportive care and antibiotics, computed tomography
      (CT)-guided percutaneous drainage, endoscopic transluminal drainage, and
      operative necrosectomy. Historically, pancreatic necrosis has been treated
      surgically. However, surgical management of pancreatic necrosis is associated
      with high mortality (6-28 %) and morbidity (19-62 %). Thus, endoscopic therapy
      has emerged as a relatively new minimally invasive technique for treating
      infected and/or symptomatic pancreatic necrosis in the last decade. Although
      there have been two randomized trials comparing endoscopic transluminal drainage
      versus operative necrosectomy, there is little data regarding timing, indication,
      and outcomes of these procedures.

PMID- 24894274
TI  - More seen within four hours, claims Scottish Government.

PMID- 24894276
TI  - Urgent care nurses given pioneering role in advanced practice.

PMID- 24894275
TI  - Inappropriate attendance rate lower than reported.

PMID- 24894277
TI  - Treat near-syncope as seriously as syncope.

PMID- 24894278
TI  - How to help in a heatwave.

PMID- 24894279
TI  - Guidance on severe constipation in children released.

PMID- 24894280
TI  - Public satisfaction falls to lowest level in past six years.

PMID- 24894281
TI  - More patients wait for longer as pressure on staff rises.

PMID- 24894282
TI  - Whistleblowers still being dismissed or redeployed, claims Patients First.

PMID- 24894283
TI  - Should people who are drunk pay for urgent treatment?

PMID- 24894284
TI  - Staffing ratios.

PMID- 24894285
TI  - Board's eye view - parallel assessments.

PMID- 24894286
TI  - The bigger picture - keep snacks out of sight.

PMID- 24894287
TI  - Making sure staff measure up.

PMID- 24894291
TI  - Diagnosis and treatment of scaphoid fracture.
AB  - Many patients with scaphoid fractures present at emergency departments but how
      they are managed can vary widely. This article reviews the literature on
      management of scaphoid injuries, discusses different types of immobilisation and
      determines best practice. 

PMID- 24894292
TI  - Ocular injuries in people with multiple trauma.
AB  - About 8% of all major trauma patients have eye injuries, which can have serious
      implications for the patients and their families. This article outlines a
      practical approach to the recognition, assessment and management in emergency
      departments of common ocular traumatic injuries. It also provides an overview of
      the applied anatomy, and discusses common complications. 

PMID- 24894294
TI  - University of life.

PMID- 24894293
TI  - Role of effective documentation in emergency departments.
AB  - Lord Laming's report into the death of Victoria Climbie highlights shortcomings
      in the safeguarding of children, in part due to poor record keeping and
      information sharing (House of Commons Health Committee 2003). This article
      presents findings from a survey of emergency department staff opinions about
      whether keeping records on children aged between birth and 16 years can safeguard
      them from harm. Staff members said that, while written records generally aid
      communication, the records they use did not focus satisfactorily on the children
      concerned and did not take into account some risks factors. The study led to a
      redesign of the record-keeping system.

PMID- 24894295
TI  - Association of neonatal red blood cell transfusion with increase in serum
      bilirubin.
AB  - BACKGROUND: It is not clear whether red blood cell (RBC) transfusions typically
      increase a neonate's total serum bilirubin (TSB) level or if so by how much.
      STUDY DESIGN AND METHODS: In this retrospective analysis, from 2009 through 2012,
      we collected TSB measurements before and after transfusions, recording blood
      types of mothers, neonates, and blood donors and whether phototherapy was used
      before, during, or after transfusion. RESULTS: Of 7272 neonates admitted during
      this period, 658 (9%) received 2597 RBC transfusions. TSB levels were drawn
      before and after 431 transfusions, 255 of which did not have phototherapy at the
      time the transfusion was administered. The mean increase in TSB was 2.2 mg/dL
      (95% confidence interval, 1.9-2.5 mg/dL). Seven percent of all transfusions and
      12% of transfusions to very-low-birthweight (VLBW) infants (<1500 g) were
      followed by a TSB increase of at least 5 mg/dL. Transfusions with "universal
      donor" blood (O-) resulted in a higher TSB increase (p < 0.0001), but the
      magnitude was clinically insignificant (0.3 mg/dL). Older blood (days since donor
      draw) did not generate significantly higher posttransfusion TSB levels (p =
      0.092). A focused study of the 10 neonates with the highest TSB increases
      revealed that six were unexplained other than transfusion related. CONCLUSIONS:
      We describe an association between RBC transfusion and TSB elevation, but we
      recognize that this does not establish a cause-and-effect relationship. However,
      the observation that an increase of at least 5 mg/dL occurs after 12% of
      transfusions to VLBW neonates suggests to us that clinicians will want to
      evaluate jaundice, or measure bilirubin, on VLBW neonates after transfusion.

PMID- 24894296
TI  - When man got his mtDNA deletions?
AB  - Somatic mtDNA mutations and deletions in particular are known to clonally expand
      within cells, eventually reaching detrimental intracellular concentrations. The
      possibility that clonal expansion is a slow process taking a lifetime had
      prompted an idea that founder mutations of mutant clones that cause mitochondrial
      dysfunction in the aged tissue might have originated early in life. If,
      conversely, expansion was fast, founder mutations should predominantly originate
      later in life. This distinction is important: indeed, from which mutations should
      we protect ourselves - those of early development/childhood or those happening at
      old age? Recently, high-resolution data describing the distribution of mtDNA
      deletions have been obtained using a novel, highly efficient method (Taylor et
      al., ). These data have been interpreted as supporting predominantly early origin
      of founder mutations. Re-analysis of the data implies that the data actually
      better fit mostly late origin of founders, although more research is clearly
      needed to resolve the controversy. 

PMID- 24894298
TI  - Metabolism of the hepatotoxic compound sophoraflavanone G in rat liver
      microsomes.
AB  - Our study aimed at investigating the metabolic characteristics of
      sophoraflavanone G (SFG), one of the hepatotoxic constituents of Sophora
      flavescens, in rat liver microsomes (RLMs). SFG was metabolized to 3 phase I
      metabolites, di-hydroxylated SFG (M1), mono-hydroxylated SFG (M2), dehydrogenated
      product of mono-hydroxylated SFG (M3) and 3 SFG glucuronides (M4, M5, and M6) by
      RLMs. The formation kinetics of M2 conformed to biphasic kinetics in RLMs. The
      formation kinetics of M4 and M5 best-fitted the Hill equation kinetics. Chemical
      inhibition studies found that CYP1A2 and CYP2E1 were the major enzymes
      responsible for the formation of M2, and the formation of M4 and M5 may be
      catalyzed by multiple UGT1A isoforms. 

PMID- 24894297
TI  - Targeting Notch1 signaling pathway positively affects the sensitivity of
      osteosarcoma to cisplatin by regulating the expression and/or activity of Caspase
      family.
AB  - BACKGROUND: The introduction of cisplatin has improved the long-term survival
      rate in osteosarcoma patients. However, some patients are intrinsically resistant
      to cisplatin. This study reported that the activation of Notch1 is positively
      correlated with cisplatin sensitivity, evidenced by both clinical and in vitro
      data. RESULTS: In this study, a total 8 osteosarcoma specimens were enrolled and
      divided into two groups according to their cancer chemotherapeutic drugs
      sensitivity examination results. The relationship between Notch1 expression and
      cisplatin sensitivity of osteosarcoma patients was detected by
      immunohistochemistry and semi-quantitative analysis. Subsequently, two typical
      osteosarcoma cell lines, Saos-2 and MG63, were selected to study the changes of
      cisplatin sensitivity by up-regulating (NICD1 plasmid transfeciton) or decreasing
      (gamma-secretase complex inhibitor DAPT) the activation state of Notch1 signaling
      pathway. Our results showed a significant correlation between the expression of
      Notch1 and cisplatin sensitivity in patient specimens. In vitro, Saos-2 with
      higher expression of Notch1 had significantly better cisplatin sensitivity than
      MG63 whose Notch1 level was relatively lower. By targeting regulation in vitro,
      the cisplatin sensitivity of Saos-2 and MG63 had significantly increased after
      the activation of Notch1 signaling pathway, and vice versa. Further mechanism
      investigation revealed that activation/inhibition of Notch1
      sensitized/desensitized cisplatin-induced apoptosis, which probably depended on
      the changes in the activity of Caspase family, including Caspase 3, Caspase 8 and
      Caspase 9 in these cells. CONCLUSIONS: Our data clearly demonstrated that Notch1
      is critical for cisplatin sensitivity in osteosarcoma. It can be used as a
      molecular marker and regulator for cisplatin sensitivity in osteosarcoma
      patients.

PMID- 24894299
TI  - Alterations of the bone dimension following immediate implant placement into
      extraction socket: systematic review and meta-analysis.
AB  - AIM: This systematic review was aimed at analysing bone dimensional alterations
      within the first year following immediate implant placement. MATERIALS AND
      METHODS: The electronic search was conducted using MEDLINE (PubMed), Cochrane
      Central Register of Controlled Trials (CENTRAL) and EMBASE from January 1980 to
      October 2013. Quality assessment of selected articles was performed using
      Cochrane Collaboration's tool or Newcastle-Ottawa scale according to the design
      of each study. A meta-analysis was performed to estimate bone dimensional
      reduction. Weighted mean differences in bone dimension between baseline and
      follow-up measurement were calculated. Subgroup analysis and mete-regression were
      conducted to evaluate the effects of different variables. RESULTS: A total of
      1348 articles were identified following the search process. Six studies were
      included in the present review. The weighted mean buccal horizontal bone
      dimensional reduction (BHDr) was 1.07 mm and buccal vertical bone dimensional
      reduction (BVDr) was 0.78 mm. The weighted mean palatal bone dimensional
      reduction was 0.62 mm horizontally (PHDr) and 0.50 mm vertically (PVDr). The
      initial thickness of the buccal alveolar plate (TB) of the socket was the only
      variable significantly correlated with BHDr and BVDr in meta-regression analysis.
      CONCLUSIONS: The bone dimensions of immediate implant sites demonstrated
      approximately 0.5-1.0 mm reduction in vertical and horizontal aspects 4-12 months
      following surgery. The results should be interpreted with care because of the
      data heterogeneity. The correlation of the socket buccal wall thickness, and
      other variables, with dimensional changes of the bony ridge should be
      investigated further in controlled clinical trials.

PMID- 24894301
TI  - [Special issue CL anniversary].

PMID- 24894300
TI  - Trimming the fat in acute ischemic stroke: an assessment of 24-h CT scans in tPA
      patients.
AB  - BACKGROUND: International management of acute ischemic stroke patients treated
      with intravenous tissue plasminogen activator frequently includes 24-h head
      imaging. These recommendations stem from the National Institute of Neurological
      Disorders and Stroke (NINDS) clinical trial protocol regarding the risk of
      intracerebral hemorrhage post-tissue plasminogen activator administration. Follow
      up computed tomography scans on select patients, however, may not effect clinical
      management, resulting in unnecessary radiation exposure and healthcare costs.
      AIMS: Our study questions the utility of routine 24-h computed tomography imaging
      and looks at the National Institute of Health Stroke Scale as a possible clinical
      screen for selecting candidates for 24-h imaging. Such a tool would result in
      decreased radiation exposure to the patient and decreased cost to the hospital.
      METHODS: Consecutive patients with acute ischemic stroke given intravenous tissue
      plasminogen activator between June 2008 and December 2011 were retrospectively
      identified and dichotomized based on change in 24-h National Institute of Health
      Stroke Scale from baseline. Initial analysis compared patients with National
      Institute of Health Stroke Scale worsening to those without worsening. Subsequent
      analysis was limited to patients with a baseline National Institute of Health
      Stroke Scale <=10. Baseline demographics and medical history, baseline and 24-h
      computed tomography findings, medical and/or surgical orders within six-hours of
      imaging, and antithrombotic administration within 24-48-h postintravenous tissue
      plasminogen activator were compared between the two groups. RESULTS: Two-hundred
      patients met inclusion criteria: No 24-h National Institute of Health Stroke
      Scale worsening (n = 167) vs. 24-h National Institute of Health Stroke Scale
      worsening (n = 33). No baseline demographic or admission data differed
      significantly between the two groups. Patients without 24-h National Institute of
      Health Stroke Scale worsening had significantly lower incidence of hemorrhagic
      infarction (10.8% vs. 31.3%, P = 0.0014) on follow-up imaging. Less than 2% of
      all patients without 24-h National Institute of Health Stroke Scale worsening had
      a parenchymal hematoma. No patient with baseline National Institute of Health
      Stroke Scale <=10 and without 24-h National Institute of Health Stroke Scale
      worsening had parenchymal hematoma. Patients with 24-h worsening were
      significantly less likely to receive timely antithrombotic therapy (60.6% vs.
      77.8%, odds ratio 0.44, 95% confidence interval 0.20-0.96). CONCLUSIONS: Our
      results demonstrate that routine 24-h computed tomography scan in patients
      without 24-h National Institute of Health Stroke Scale worsening (especially
      those with baseline National Institute of Health Stroke Scale <=10) is less
      likely to yield information that results in a deviation from standard acute
      stroke care. No patient without worsening and baseline National Institute of
      Health Stroke Scale <=10 had parenchymal hematoma on 24-h computed tomography.
      Application of the National Institute of Health Stroke Scale to distinguish
      patients who should have 24-h follow-up imaging from those who will not benefit
      is a potential avenue for improving utilization of resources and warrants further
      study.

PMID- 24894302
TI  - [A message from Dr. Enrique Ruelas Barajas at the opening ceremony of the CLI
      academic year and the beginning of the CL year celebration of the National
      Academy of Medicine].

PMID- 24894303
TI  - [Why must we celebrate the 150 years from the National Academy of Medicine of
      Mexico foundation?].

PMID- 24894304
TI  - [Participation of the Mexican National Academy of Medicine in the accreditation
      of medical specialties and the certification of medical specialists].
AB  - We present a brief biography of the prominent Mexican doctor Miguel Francisco
      Jimenez. Because of his great academic contributions and medical achievements,
      the Mexican National Academy of Medicine named its annual lecture to welcome its
      new members after him. We also provide insights on the inception of Medical
      Boards for certification and medical specialties, emphasizing the Mexican
      situation. The Mexican National Academy of Medicine has had an important role in
      the organization, development, and recognition of these boards by official health
      authorities. Finally, we explain how the Advisory Committee of The National Board
      for Medical Specialties (CONACEM) functions, and how it has become a relevant
      auxiliary body within the Federal Government. 

PMID- 24894305
TI  - [Gaceta Medica de Mexico along the years. About the cause of death from large
      height falls. 1875].

PMID- 24894306
TI  - Shifting from quinine to artesunate as first-line treatment of severe malaria in
      children and adults: saving more lives.
AB  - Severe malaria kills more than a half million people each year. Based on high
      quality evidence of the efficacy superiority of artesunate over quinine in adults
      and children with severe malaria, the World Health Organization guidelines have
      been revised. The WHO currently recommends injectable artesunate as the first
      line treatment for severe malaria. Since this revision in April 2011, only a
      small number of countries affected by malaria have adopted and implemented the
      new policy. If this policy is implemented, an additional 195,000 lives would be
      saved each year in Africa. Thus, there is an urgent need to speed up access to
      injectable artesunate in malaria-endemic countries. This review presents a
      background for recommending artesunate as the first-line treatment of severe
      malaria in children and adults, and interventions that are recommended to
      accelerate access to injectable artesunate. 

PMID- 24894307
TI  - Inhibition of Pseudomonas aeruginosa PAO1 adhesion to and invasion of A549 lung
      epithelial cells by natural extracts.
AB  - Pseudomonas aeruginosa colonizes the lungs in cystic fibrosis (CF) and
      mechanically ventilated patients by binding to the cellular receptors on the
      surface of the lung epithelium. Studies have shown that blocking this interaction
      could be achieved with sub-minimum inhibitory concentrations of antibiotics such
      as ciprofloxacin. The development of bacterial resistance is a probable drawback
      of such an intervention. The use of natural extracts to interfere with bacterial
      adhesion and invasion has recently gained substantial attention and is
      hypothesized to inhibit bacterial binding and consequently prevent or reduce
      pathogenicity. This study used an A549 lung epithelial cell infection model, and
      the results revealed that a combination of aqueous cranberry extract with
      ciprofloxacin could completely prevent the adhesion and invasion of P. aeruginosa
      PAO1 compared to the untreated control. All of the natural extracts (cranberry,
      dextran, and soybean extracts) and ciprofloxacin showed a significant reduction
      (P<0.0001) in P. aeruginosa PAO1 adhesion to and invasion of lung epithelial
      cells relative to the control. The cranberry, dextran, and soybean extracts could
      substantially increase the anti-adhesion and anti-invasion effects of
      ciprofloxacin to the averages of 100% (P<0.0001), 80% (P<0.0001), and 60%
      (P<0.0001), respectively. Those extracts might result in a lower rate of the
      development of bacterial resistance; they are relatively safe and inexpensive
      agents, and utilizing such extracts, alone or in combination with ciprofloxacin,
      as potential anti-adhesion and anti-invasion remedies, could be valuable in
      preventing or reducing P. aeruginosa lung infections. 

PMID- 24894308
TI  - Role of auditory non-verbal working memory in sentence repetition for bilingual
      children with primary language impairment.
AB  - BACKGROUND: Sentence repetition performance is attracting increasing interest as
      a valuable clinical marker for primary (or specific) language impairment (LI) in
      both monolingual and bilingual populations. Multiple aspects of memory appear to
      contribute to sentence repetition performance, but non-verbal memory has not yet
      been considered. AIMS: To explore the relationship between a measure of non
      verbal auditory working memory (NVWM) and sentence repetition performance in a
      sample of bilingual children with LI. METHODS & PROCEDURES: Forty-seven school
      aged Spanish-English bilingual children with LI completed sentence repetition and
      non-word repetition tasks in both Spanish and English as well as an NVWM task.
      Hierarchical multiple linear regression was used to predict sentence repetition
      in each language using age, non-word repetition and NVWM. OUTCOMES & RESULTS:
      NVWM predicted unique variance in sentence repetition performance in both
      languages after accounting for chronological age and language-specific
      phonological memory, as measured by non-word repetition. CONCLUSIONS &
      IMPLICATIONS: Domain-general memory resources play a unique role in sentence
      repetition performance in children with LI. Non-verbal working memory weaknesses
      may contribute to the poor performance of children with LI on sentence repetition
      tasks.

PMID- 24894309
TI  - The association between systemic sclerosis and bone mineral density- a meta
      analysis of observational studies.
AB  - Previous research has shown inconsistent effect of systemic sclerosis (SSc) on
      bone mineral density (BMD). The objective of this study was to perform a meta
      analysis of previous articles to investigate the differences in BMD (g/cm(2) )
      between SSc and non-SSc populations and to discuss potential underlying
      mechanisms. Twelve full-text articles (including an outlier study and two studies
      with identical data) with 662 SSc patients and 886 controls were identified by
      searching Medline prior to 10 September, 2013 using search terms 'Systemic
      sclerosis' OR 'scleroderma' and 'osteoporosis' OR 'bone density' OR 'bone mass'.
      BMD (mean and standard deviation), T-scores and Z-scores at lumbar spine, femoral
      neck and total hip measured by dual-energy X-ray absorptiometry were extracted.
      Meta-analysis showed that a lower level of BMD was found in SSc patients, with
      weighted mean difference of -0.343 (95% CI: -0.500 to -0.186) at femoral neck, 
      0.084 (95% CI: -0.110 to -0.057) at total hip and -0.104 (95% CI: -0.135 to 
      0.073) at the lumbar spine. We conclude that patients with SSc may have a lower
      BMD level than healthy controls. 

PMID- 24894310
TI  - Effectiveness and efficiency of integrated mental health care programmes in
      Germany: study protocol of an observational controlled trial.
AB  - BACKGROUND: Since 2009 some German health insurance companies have implemented
      integrated mental health care services along the principles of assertive
      community treatment in collaboration with local mental health service providers
      across Germany. Focus of this study is the analysis of effectiveness and cost
      effectiveness of this integrated care programme compared to care as usual in
      routine care surroundings in five regions in Germany. METHODS: In this 18-month
      multi-centre observational trial 250 patients enrolled in an integrated mental
      health care programme and 250 patients who receive treatment as usual from five
      catchment areas will be included. In addition, in each group about 125 relatives
      of the participating patients will be included. The primary outcome criterion is
      the improvement of empowerment; secondary outcomes are subjective quality of
      life, functional impairment and costs of illness. Data will be collected at
      baseline and three follow-ups after 6, 12 and 18 months. Data will be analysed by
      means of mixed effects regression models. Propensity score methods are used for
      selection bias control. DISCUSSION: Study results are expected to provide
      information about how integrated care programmes in their present form contribute
      to the improvement of mental health care. In addition, the study will provide
      hints to weaknesses of the current integrated care programme and options to
      overcome them. The major strengths of this study are the real-world character of
      the study intervention with a simultaneous high level of academic rigour.
      However, the fact that patients are not randomised to study groups and that there
      is no blinding might limit the study. TRIAL REGISTRATION: German Clinical Trial
      Register DRKS00005111.

PMID- 24894311
TI  - Clinical characteristics and treatment outcome in 65 cases with refractory
      cytopenia of childhood defined according to the WHO 2008 classification.
AB  - This study analysed 65 children who were prospectively registered between 1999
      and 2008 and fulfilled the World Health Organization 2008 criteria of refractory
      cytopenia of childhood (RCC). First-line therapy was determined by the treating
      physicians: 25 patients received immunosuppressive therapy (IST), 12 patients
      received haematopoietic stem cell transplantation (HSCT) and one patient received
      intensive chemotherapy. The remaining 27 patients were followed without treatment
      for more than 2 years (watch and wait; WW). In the WW group, 18 patients had
      stable disease without further intervention. Thirteen of 29 patients (45%) who
      ended up receiving IST showed response. The combination of ciclosporin and
      antithymocyte globulin was not shown to be superior to ciclosporin alone with
      regard to response rate or survival. Of 28 patients who ended up undergoing HSCT,
      17 patients are alive in complete remission, whereas nine patients died mostly
      due to transplantation-related mortality. The 5-year overall survival for all
      patients was 82 +/- 5%. Eight patients suffered from disease progression.
      Patients with monosomy 7 or multilineage-dysplasia had a significantly higher
      incidence of disease progression. This analysis revealed heterogeneity in the
      clinical course of RCC, varying from those who remained stable for long periods
      to those who progressed to advanced disease.

PMID- 24894313
TI  - Radiographic features of pulmonary embolism: Hampton's hump.

PMID- 24894312
TI  - The impact of endoscopic sinus surgery on health care use in patients with
      respiratory comorbidities.
AB  - OBJECTIVE: Analyze health care needs and outcomes-defined by changes in health
      care utilization-in cohorts of patients with respiratory comorbidities and
      requiring sinus surgery for the treatment of chronic rhinosinusitis (CRS). STUDY
      DESIGN: Retrospective database analysis. SETTING: US-wide claims database
      (MarketScan). SUBJECTS AND METHODS: All patients with endoscopic sinus surgery
      (CPT 31254-31288) in 2008 and at least 2 years of continuous enrollment prior and
      post surgery were analyzed for concurrent comorbidities (asthma, polyps, aspirin
      sensitivity, and allergies). Inpatient and outpatient events as well as
      prescriptions related to the treatment of CRS were analyzed for frequency and
      cost, based on respiratory comorbidities. RESULTS: A total of 9105 patients were
      included and subdivided as following: no respiratory comorbidity (N = 4780),
      asthma only (N = 1167), polyps and asthma (N = 721), Samter's triad (N = 91), and
      additional subgroups based on various combinations of concurrent comorbidities.
      Before surgery, costs were flat, ranging from $296.4 (95% CI, $263.1-$329.8) per
      patient per year for patients in the no comorbidity group to $2189 (95% CI,
      $1449.2-$2930.1) for patients with Samter's triad. Surgery was preceded by at
      least 6 months of increased health care utilization (outpatient care and
      prescriptions). Following surgery, health care needs declined rapidly and reached
      baseline levels within 3 to 4 postoperative months. Patients with asthma received
      significantly more health care for CRS than patients without asthma through the
      entire study. CONCLUSIONS: Patients with CRS incur continuous costs and health
      care needs, due to the chronic nature of their disease. All patients, regardless
      of comorbidity, experienced significant decline in health care needs following
      sinus surgery from their preoperative state.

PMID- 24894315
TI  - Eighth Bone Quality Seminar Proceedings 2013.

PMID- 24894314
TI  - Upper gastrointestinal bleeding in hospital inpatients: the role of
      antithrombotic drugs.
AB  - BACKGROUND: Critically ill patients are considered to be most at risk from
      developing non-variceal upper gastrointestinal bleeding (NVGIB) while in
      hospital. The increasing prescription of low-dose aspirin and other
      antithrombotic drugs for protection against thromboembolism to many patients
      admitted to hospital may increase the vulnerability of a wider group to NVGIB.
      OBJECTIVE: This study compares two groups of patients with NVGIB: group I,
      inpatients cared for outside the intensive care unit; and group II, patients
      admitted with this condition, while considering the use of antithrombotic drugs.
      METHODS: We identified all patients who developed NVGIB in the two calendar years
      between 2008 and 2009 and compared group I with group II while taking into
      account their clinical details including Rockall scores and drug usage. RESULTS:
      Compared with group II (n=274), group I (n=96) were older (median age of 77 years
      vs 68; p<0.001), had fewer males (45.8% vs 60.6%; p=0.016), higher prevalence of
      cardiovascular disease (52.1% vs 29.2%; p<0.001), more patients with complete
      Rockall score >= 3 (84.4% vs 66.7%; p=0.001) and more patients treated with
      aspirin or other antithrombotic drugs (64.6% vs 44.5%; p=0.001). After adjustment
      for age and sex, group I were still significantly more likely to be taking
      antithrombotic drugs than group II (OR (95% CIs), 2.15 (1.25 to 3.68); p=0.006).
      The endoscopic abnormalities in more than 80% of patients included erosive
      oesophagitis, gastric or duodenal ulcers or erosions. CONCLUSIONS: Subjects who
      develop NVGIB as inpatients have higher Rockall scores are mainly older females
      with cardiovascular disease and using antithrombotic drugs. Secondary care
      clinicians should be mindful of this at-risk group of patients and consider
      giving them prophylactic antiulcer therapy.

PMID- 24894316
TI  - Across-year social stability shapes network structure in wintering migrant
      sparrows.
AB  - Migratory birds often form flocks on their wintering grounds, but important
      details of social structure such as the patterns of association between
      individuals are virtually unknown. We analysed networks of co-membership in short
      term flocks for wintering golden-crowned sparrows (Zonotrichia atricapilla)
      across three years and discovered social complexity unsuspected for migratory
      songbirds. The population was consistently clustered into distinct social
      communities within a relatively small area (~ 7 ha). Birds returned to the same
      community across years, with mortality and recruitment leading to some degree of
      turnover in membership. These spatiotemporal patterns were explained by the
      combination of space use and social preference - birds that flocked together in
      one year flocked together again in the subsequent year more often than were
      expected based on degrees of home range overlap. Our results suggest that a
      surprising level of social fidelity across years leads to repeatable patterns of
      social network structure in migratory populations. 

PMID- 24894319
TI  - NEAT in need of a sweet spot.

PMID- 24894317
TI  - RIG-I-like receptors and negative-strand RNA viruses: RLRly bird catches some
      worms.
AB  - Negative strand RNA viruses with a nonsegmented genome (ns-NSVs) or a segmented
      genome (s-NSVs) are an important source of human and animal diseases. Survival of
      the host from those infections is critically dependent on rapidly reacting innate
      immune responses. Two cytoplasmic RNA helicases, RIG-I and MDA5 (collectively
      termed RIG-I-like receptors, RLRs), are essential for recognizing virus-specific
      RNA structures to initiate a signalling cascade, resulting in the production of
      the antiviral type I interferons. Here, we will review the current knowledge and
      views on RLR agonists, RLR signalling, and the wide variety of countermeasures ns
      NSVs and s-NSVs have evolved. Specific aspects include the consequences of genome
      segmentation for RLR activation and a discussion on the physiological ligands of
      RLRs.

PMID- 24894320
TI  - smaccGOLD and the rise of the Synthetics.

PMID- 24894321
TI  - Emergency healthcare of the future.
AB  - Emergency healthcare is a high profile component of modern healthcare systems,
      which over the past three decades has fundamentally transformed in many
      countries. However, despite this rapid development, and associated investments in
      service standards, there is a high level of concern with the performance of
      emergency health services relating principally to system wide congestion. The
      factors driving this problem are complex but relate largely to the combined
      impact of growing demand, expanded scope of care and blocked access to inpatient
      beds. These factors are unlikely to disappear in the medium term despite the
      National Emergency Access Target. The aim of this article is to stimulate a
      conversation about the future design and functioning of emergency healthcare
      systems; examining what we understand about the problem and proposing a rationale
      that may underpin future strategic approaches. This is also an invitation to join
      the conversation. 

PMID- 24894322
TI  - Is National Emergency Access Target dumbing down emergency physicians?

PMID- 24894324
TI  - Monitoring of therapy in atopic dermatitis--observations with the use of high
      frequency ultrasonography.
AB  - BACKGROUND: In reactive and proactive therapy of atopic dermatitis a well
      established agent is tacrolimus, a member of calcineurin inhibitors' family. The
      clinical safety and efficacy of this drug were evaluated previously in randomized
      multicenter trials. However, so far in clinical studies the assessment of its
      action on the skin has been made only on the basis of different scores and
      scales. We present the 6-month observations of tacrolimus therapy in atopic
      dermatitis patients monitored with the use of noninvasive techniques like high
      frequency ultrasonography and evaporimetry. METHODS: The study consisted of 39
      patients with AD and their mean age was 26.3 +/- 12.8 years. The study lasted 6
      months and every 4 weeks patient visited the outpatient clinic (totally 7
      visits). The evaluation of disease severity within right antecubital fossa was
      obtained on the basis of Investigator's Global Assessment (IGA) score. During
      every control visit noninvasive measurements were carried in the form of HF-USG
      (with determination of subepidermal low echogenic band, SLEB) and evaporimetry.
      RESULTS: 39 patients started the study and 22 of them (54.6%) finished it. Out of
      39 patients, 31 (79.5%) received at least 4 week long proactive treatment. We
      observed statistically significant change of IGA, mean SLEB value and TEWL during
      underwent therapy. There were also statistically significant differences in mean
      SLEB and TEWL values between lesional and nonlesional measures. CONCLUSIONS: This
      report shows the usefulness of HF-USG in monitoring tacrolimus therapy in atopic
      dermatitis. It is worth emphasizing, that this tool is easily reproducible and
      allows clinicians to visualize pathologic changes of all skin in vivo. As a
      noninvasive and independent of subjective judgment method, HF-USG should be
      included in overall evaluation of atopic dermatitis disease severity together
      with common scores or scales, especially in the era of evidence based medicine.

PMID- 24894325
TI  - A decrease in the size of ground glass nodules may indicate the optimal timing
      for curative surgery.
AB  - OBJECTIVES: Although ground glass nodules (GGNs) are generally considered to grow
      slowly to a large size, their natural progression remains unclear, and a decrease
      in tumor size has been reported in a few previous studies. The study aimed to
      retrospectively review the radiologic and pathological characteristics of
      resected ground glass nodules (GGNs) followed with chest computed tomography (CT)
      for at least a year before surgery to clarify the natural progression of GGNs.
      PATIENTS AND METHODS: The chest CT cans and clinical charts of 32 GGNs in 31
      patients who underwent pulmonary resection between January 2006 and March 2013
      were retrospectively reviewed. The definitions of pure GGNs and part-solid
      nodules were based on the tumor shadow disappearance rate. The tumor size was
      measured twice, and the mean size was used for evaluation. RESULTS: The mean GGN
      size before surgery was 15.2 mm, and the median follow-up period before surgery
      was 21 months. In the follow-up period, 15 (58%) of 26 pure GGNs at the initial
      CT remained pure GGNs at the last CT. However, a solid component appeared in the
      remaining 11 tumors (42%) of the 26 initial pure GGNs. Furthermore, 1 GGN of the
      15 GGNs that remained pure and 10 of the 11 GGNs with solid component also showed
      a size decrease. In addition, 6 part-solid nodules were observed at the initial
      CT. Of these, 3 showed a decrease in size during follow-up. Overall, 47% of the
      GGNs showed a size reduction on follow-up chest CT. CONCLUSIONS: A size reduction
      was observed in nearly half of the GGNs and suggested the progression to an
      invasive adenocarcinoma. When a mild collapse of the GGNs is observed, a careful
      follow-up is necessary to identify a solid component. Tumor size decreases may
      represent the optimal timing of pulmonary resection for curative treatment.

PMID- 24894327
TI  - From CNS stem cells to neurons and glia: Sox for everyone.
AB  - Neuroepithelial precursor cells of the vertebrate central nervous system either
      self-renew or differentiate into neurons, oligodendrocytes or astrocytes under
      the influence of a gene regulatory network that consists in transcription
      factors, epigenetic modifiers and microRNAs. Sox transcription factors are
      central to this regulatory network, especially members of the SoxB, SoxC, SoxD,
      SoxE and SoxF groups. These Sox proteins are widely expressed in neuroepithelial
      precursor cells and in newly specified, differentiating and mature neurons,
      oligodendrocytes and astrocytes and influence their identity, survival and
      development. They exert their effect predominantly at the transcriptional level
      but also have substantial impact on expression at the epigenetic and
      posttranscriptional levels with some Sox proteins acting as pioneer factors,
      recruiting chromatin-modifying and -remodelling complexes or influencing microRNA
      expression. They interact with a large variety of other transcription factors and
      influence the expression of regulatory molecules and effector genes in a cell
      type-specific and temporally controlled manner. As versatile regulators with
      context-dependent functions, they are not only indispensable for central nervous
      system development but might also be instrumental for the development of
      reprogramming and cell conversion strategies for replacement therapies and for
      assisted regeneration after injury or degeneration-induced cell loss in the
      central nervous system. 

PMID- 24894326
TI  - Clinical features, anti-cancer treatments and outcomes of lung cancer patients
      with combined pulmonary fibrosis and emphysema.
AB  - BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) patients may be at
      significantly increased risk of lung cancer compared with either isolated
      emphysema or pulmonary fibrosis patients. Acute exacerbation (AE) of interstitial
      lung disease caused by anticancer treatment is the most common lethal
      complication in Japanese lung cancer patients. Nevertheless, the clinical
      significance of CPFE compared with isolated idiopathic interstitial pneumonias
      (IIPs) in patients with lung cancer is not well understood. METHODS: A total of
      1536 patients with lung cancer at Nippon Medical School Hospital between March
      1998 and October 2011 were retrospectively reviewed. Patients with IIPs were
      categorized into two groups: (i) CPFE; IIP patients with definite emphysema and
      (ii) non-CPFE; isolated IIP patients without definite emphysema. The clinical
      features, anti-cancer treatments and outcomes of the CPFE group were compared
      with those of the non-CPFE group. RESULTS: CPFE and isolated IIPs were identified
      in 88 (5.7%) and 63 (4.1%) patients respectively, with lung cancer. AE associated
      with initial treatment occurred in 22 (25.0%) patients in the CPFE group and in 8
      (12.7%) patients in the non-CPFE group, irrespective of treatment modality.
      Median overall survival (OS) of the CPFE group was 23.7 months and that of the
      non-CPFE group was 20.3 months (P=0.627). Chemotherapy was performed in a total
      of 83 patients. AE associated with chemotherapy for advanced lung cancer occurred
      in 6 (13.6%) patients in the CPFE group and 5 (12.8%) patients in the non-CPFE
      group. Median OS of the CPFE group was 14.9 months and that of the non-CPFE group
      was 21.6 months (P=0.679). CONCLUSION: CPFE was not an independent risk factor
      for AE and was not an independent prognosis factor in lung cancer patients with
      IIPs. Therefore, great care must be exercised with CPFE as well as IIP patients
      when performing anticancer treatment for patients with lung cancer.

PMID- 24894330
TI  - Developing the radiation protection safety culture in the UK.
AB  - In the UK, as elsewhere, there is potential to improve how radiological
      challenges are addressed through improvement in, or development of, a strong
      radiation protection (RP) safety culture. In preliminary work in the UK, two
      areas have been identified as having a strong influence on UK society: the
      healthcare and nuclear industry sectors. Each has specific challenges, but with
      many overlapping common factors. Other sectors will benefit from further
      consideration.In order to make meaningful comparisons between these two principal
      sectors, this paper is primarily concerned with cultural aspects of RP in the
      working environment and occupational exposures rather than patient doses.The
      healthcare sector delivers a large collective dose to patients each year,
      particularly for diagnostic purposes, which continues to increase. Although
      patient dose is not the focus, it must be recognised that collective patient dose
      is inevitably linked to collective occupational exposure, especially in
      interventional procedures.The nuclear industry faces major challenges as work
      moves from operations to decommissioning on many sites. This involves restarting
      work in the plants responsible for the much higher radiation doses of the
      1960/70s, but also performing tasks that are considerably more difficult and
      hazardous than those original performed in these plants.Factors which influence
      RP safety culture in the workplace are examined, and proposals are considered for
      a series of actions that may lead to an improvement in RP culture with an
      associated reduction in dose in many work areas. These actions include methods to
      improve knowledge and awareness of radiation safety, plus ways to influence
      management and colleagues in the workplace. The exchange of knowledge about
      safety culture between the nuclear industry and medical areas may act to develop
      RP culture in both sectors, and have a wider impact in other sectors where
      exposures to ionising radiations can occur. 

PMID- 24894331
TI  - Sequential in vivo imaging of osteogenic stem/progenitor cells during fracture
      repair.
AB  - Bone turns over continuously and is highly regenerative following injury.
      Osteogenic stem/progenitor cells have long been hypothesized to exist, but in
      vivo demonstration of such cells has only recently been attained. Here, in vivo
      imaging techniques to investigate the role of endogenous osteogenic
      stem/progenitor cells (OSPCs) and their progeny in bone repair are provided.
      Using osteo-lineage cell tracing models and intravital imaging of induced
      microfractures in calvarial bone, OSPCs can be directly observed during the first
      few days after injury, in which critical events in the early repair process
      occur. Injury sites can be sequentially imaged revealing that OSPCs relocate to
      the injury, increase in number and differentiate into bone forming osteoblasts.
      These methods offer a means of investigating the role of stem cell-intrinsic and
      extrinsic molecular regulators for bone regeneration and repair. 

PMID- 24894332
TI  - Genetic testing and familial implications in breast-ovarian cancer families.
AB  - DNA-testing for BRCA1 and BRCA2 has become incorporated in the diagnostic
      procedure of patients with breast and/or ovarian cancer. Since 1994 an immense
      amount of information has been gathered on mutation spectra, mutation risk
      assessment, cancer risks for mutation carriers, factors that modify these risks,
      unclassified DNA variants, surveillance strategies and preventive options. For
      the patient and family the main determinator still is whether a mutation is found
      or not. When a pathogenic mutation is detected in an index case, relatives can
      opt for pre-symptomatic DNA testing. However in the vast majority no mutation, or
      only unclear mutations are detectable yet. This means that a hereditary cause
      cannot be excluded, but pre-symptomatic DNA-testing is still unavailable for
      relatives. Surveillance for both index cases and relatives is based of the family
      history of cancer. Next generation genetic testing may help to elucidate genetic
      causes in these families.

PMID- 24894333
TI  - Manufacture of concentrated, lipid-based oxygen microbubble emulsions by high
      shear homogenization and serial concentration.
AB  - Gas-filled microbubbles have been developed as ultrasound contrast and drug
      delivery agents. Microbubbles can be produced by processing surfactants using
      sonication, mechanical agitation, microfluidic devices, or homogenization.
      Recently, lipid-based oxygen microbubbles (LOMs) have been designed to deliver
      oxygen intravenously during medical emergencies, reversing life-threatening
      hypoxemia, and preventing subsequent organ injury, cardiac arrest, and death. We
      present methods for scaled-up production of highly oxygenated microbubbles using
      a closed-loop high-shear homogenizer. The process can produce 2 L of concentrated
      LOMs (90% by volume) in 90 min. Resulting bubbles have a mean diameter of ~2 MUm,
      and a rheologic profile consistent with that of blood when diluted to 60 volume
      %. This technique produces LOMs in high capacity and with high oxygen purity,
      suggesting that this technique may be useful for translational research labs. 

PMID- 24894336
TI  - Investigating the effectiveness of response strategies for vulnerabilities to
      corruption in the chinese public construction sector.
AB  - Response strategy is a key for preventing widespread corruption vulnerabilities
      in the public construction sector. Although several studies have been devoted to
      this area, the effectiveness of response strategies has seldom been evaluated in
      China. This study aims to fill this gap by investigating the effectiveness of
      response strategies for corruption vulnerabilities through a survey in the
      Chinese public construction sector. Survey data obtained from selected experts
      involved in the Chinese public construction sector were analyzed by factor
      analysis and partial least squares-structural equation modeling. Analysis results
      showed that four response strategies of leadership, rules and regulations,
      training, and sanctions, only achieved an acceptable level in preventing
      corruption vulnerabilities in the Chinese public construction sector. This study
      contributes to knowledge by improving the understanding of the effectiveness of
      response strategies for corruption vulnerabilities in the public construction
      sector of developing countries. 

PMID- 24894337
TI  - Photo-physical properties of 2-(1-ethynylpyrene)-adenosine: influence of hydrogen
      bonding on excited state properties.
AB  - The photo-physical properties of 2-(1-ethynylpyrene)-adenosine (PyA), a
      fluorescent probe for RNA dynamics, were examined by solvation studies. The
      excited-state dynamics display the influence of the vicinity on the spectral
      features. Combining improved transient absorption and streak camera measurements
      along with a new analysis method provide a detailed molecular picture of the
      photophysics. After intramolecular vibrational energy redistribution (IVR), two
      distinct states are observed. Solvent class (protic/aprotic) and permittivity
      strongly affect the properties of these states and their population ratio. As a
      result their emission spectrum is altered, while the fluorescence quantum yield
      and the overall lifetime remain nearly unchanged. Consequently, the hitherto
      existing model of the photophysics is herein refined and extended. The findings
      can serve as basis for improving the information content of measurements with PyA
      as a label in RNA. 

PMID- 24894338
TI  - Current thawing and infusion practice of cryopreserved cord blood: the impact on
      graft quality, recipient safety, and transplantation outcomes.
AB  - Methods of handling, thawing, and infusion of cord blood (CB) products vary
      substantially among thaw/transplant centers (TCs). This review 1) compares
      currently available CB product types and thaw methods recommended by CB banks
      (CBBs), 2) discusses causes of inconsistency in thaw method application at TCs,
      3) advises elements to consider in thaw method approval or selection at the TC,
      4) provides a procedural template for the traditional thaw methods, and 5)
      suggests acceptable time from product thaw to infusion and other considerations
      for safe infusion. It also compares postinfusion adverse reaction and engraftment
      data as functions of thaw methods. Remarks and suggestions made throughout this
      review are: 1) not intended to supersede manufacturer's instructions but meant to
      support the standardization of preparative procedures recommended by CBBs and 2)
      intended to help TCs to investigate relevant quality issues and handle
      challenges, especially when the TC is unable to follow recommendations due to
      foreseeable technical, quality, and/or clinical factors. 

PMID- 24894339
TI  - Fecal microbiome analysis as a diagnostic test for diverticulitis.
AB  - Disease-specific variations in intestinal microbiome composition have been found
      for a number of intestinal disorders, but little is known about diverticulitis.
      The purpose of this study was to compare the fecal microbiota of diverticulitis
      patients with control subjects from a general gastroenterological practice and to
      investigate the feasibility of predictive diagnostics based on complex microbiota
      data. Thirty-one patients with computed tomography (CT)-proven left-sided
      uncomplicated acute diverticulitis were included and compared with 25 control
      subjects evaluated for a range of gastrointestinal indications. A high-throughput
      polymerase chain reaction (PCR)-based profiling technique (IS-pro) was performed
      on DNA isolates from baseline fecal samples. Differences in bacterial phylum
      abundance and diversity (Shannon index) of the resulting profiles were assessed
      by conventional statistics. Dissimilarity in microbiome composition was analyzed
      with principal coordinate analysis (PCoA) based on cosine distance measures. To
      develop a prediction model for the diagnosis of diverticulitis, we used cross
      validated partial least squares discriminant analysis (PLS-DA).
      Firmicutes/Bacteroidetes ratios and Proteobacteria load were comparable among
      patients and controls (p = 0.20). The Shannon index indicated a higher diversity
      in diverticulitis for Proteobacteria (p < 0.00002) and all phyla combined (p =
      0.002). PCoA based on Proteobacteria profiles resulted in visually separate
      clusters of patients and controls. The diagnostic accuracy of the cross-validated
      PLS-DA regression model was 84 %. The most discriminative species derived largely
      from the family Enterobacteriaceae. Diverticulitis patients have a higher
      diversity of fecal microbiota than controls from a mixed population, with the
      phylum Proteobacteria defining the difference. The analysis of intestinal
      microbiota offers a novel way to diagnose diverticulitis.

PMID- 24894340
TI  - Occurrence of female genital tuberculosis among infertile women: a study from a
      tertiary maternal health care research centre in South India.
AB  - The purpose of this investigation was to estimate the proportion of female
      genital tuberculosis (FGTB) among infertile women, along with the mean cost of
      diagnosis by different methods. The study was carried out on 211,335 women, of
      which 31,755 (15.02 %) were infertile. 202 women were highly suspected of FGTB on
      laparoscopy, which was later ascertained by multi-gene polymerase chain reaction
      (PCR), and the cost was estimated. The majority of the patients were infertile
      (77.23 %), with menstrual disturbances (61.88 %). Many of them were having beaded
      tubes (68.81 %), tubal block with hydrosalpinx (58.91 %) and tubercular
      salpingitis (48.01 %). Out of 302 case-controls, 105 infertile women were
      positive by haematoxylin and eosin staining, 14.57 % were acid-fast bacilli
      positive and 86 infertile women were positive on culture. 178 (58.94 %) endo
      ovarian tissue biopsies and pelvic aspirated fluid specimens were positive for a
      32-kDa protein gene as amplified using multi-gene PCR. The proportion of proven
      FGTB cases was very high (58.94 %) among infertile women highly suspected of
      FGTB. The estimated cost in rupees (Rs) of FGTB diagnosis by the conventional
      method ranges from Rs 3.36 to 38.11, while multi-gene PCR was established as
      being very expensive (Rs 254.21). The expected time of FGTB diagnosis by the
      conventional method ranges from 0.5 to 1.83 h, whereas culture took 4-8 weeks.
      The logical time of FGTB diagnosis by multi-gene PCR was 6.48 h. Compared to
      Ziehl-Neelsen's staining and culturing, multi-gene PCR improved the detection
      rate of suspected FGTB. Therefore, FGTB can be diagnosed if multi-gene PCR is
      considered in the evaluation of infertile patients in areas where tuberculosis is
      endemic.

PMID- 24894341
TI  - Increasing incidence of hemorrhagic fever with renal syndrome could be associated
      with livestock husbandry in Changchun, northeastern China.
AB  - BACKGROUND: Since the end of the 1990s, the incidence of hemorrhagic fever with
      renal syndrome (HFRS) has been increasing dramatically in Changchun, northeastern
      China. However, it is unknown which, and how, underlying risk factors have been
      involved in the reemergence of the disease. METHODS: Data on HFRS cases at the
      county scale were collected from 1998 to 2012. Data on livestock husbandry
      including the numbers of large animals (cattle, horses, donkeys and mules),
      sheep, and deer, and on climatic and land cover variables were also collected.
      Epidemiological features, including the spatial, temporal and human patterns of
      disease were characterized. The potential factors related to spatial
      heterogeneity and temporal trends were analyzed using standard and time-series
      Poisson regression analysis, respectively. RESULTS: Annual incidence varied among
      the 10 counties. Shuangyang County in southeastern Changchun had the highest
      number of cases (1,525 cases; 35.9% of all cases), but its population only
      accounted for 5.6% of the total population. Based on seasonal pattern in HFRS
      incidence, two epidemic phases were identified. One was a single epidemic peak at
      the end of each year from 1988 to 1997 and the other consisted of dual epidemic
      peaks at both the end and the beginning of each year from 1998 to the end of the
      study period. HFRS incidence was higher in males compared to females, and most of
      the HFRS cases occurred in peasant populations. The results of the Poisson
      regression analysis indicated that the spatial distribution and the increasing
      incidence of HFRS were significantly associated with livestock husbandry and
      climate factors, particularly with deer cultivation. CONCLUSIONS: Our results
      indicate that the re-emergence of HFRS in Changchun has been accompanied by
      changing seasonal patterns over the past 25 years. Integrated measures focusing
      on areas related to local livestock husbandry could be helpful for the prevention
      and control of HFRS.

PMID- 24894343
TI  - A multi-institutional study on the association between BRCA1/BRCA2 mutational
      status and triple-negative breast cancer in familial breast cancer patients.
AB  - Triple-negative breast cancer (TNBC) accounts for 12-24 % of all breast cancers.
      Here, we studied 221 familial breast and/or ovarian cancer patients from 37
      hospitals using a comprehensive approach to identify large genomic rearrangements
      (LGRs) as well as sequence variants, and investigated the association between
      BRCA1/2 mutational status and TNBC. We performed direct sequencing or mutation
      scanning followed by direct sequencing. Then, 143 BRCA1/2 mutation-negative
      patients were screened for LGRs. In this study, the prevalence of BRCA1/2
      mutations was high (36.9 %). The prevalence of BRCA1 mutations was similar to
      that of BRCA2 mutations: 49.4 versus 50.6 %, respectively. TNBC was diagnosed in
      35.2 % of BRCA1/2 mutation carriers and 57.1 % of BRCA1 mutation carriers.
      Conversely, two-thirds of TNBC patients carried BRCA1/2 mutation(s), and about
      half were BRCA1 mutation carriers. When stratified by the mutated gene, TNBC
      prevalence in BRCA1 mutation carriers was significantly lower when there was a
      family history of ovarian cancer. Our multinomial logistic regression model
      demonstrated that no single factor was sufficient, and at least two factors, such
      as a patient with family history of both breast cancer and ovarian cancer or a
      patient diagnosed at a relatively young age (<40 years) with a TNBC phenotype,
      are necessary to indicate BRCA1/2 genetic testing in this population. Our results
      suggest that TNBC is a strong predictor for the presence of a BRCA1 mutation in
      this population, but additional risk factors should also be evaluated to
      ascertain a 10 % or higher prior probability of BRCA1/2 mutation testing. 

PMID- 24894344
TI  - Erythropoietin-stimulating agents in the management of anemia of end-stage renal
      disease patients on regular hemodialysis: a prospective randomized comparative
      study from Qatar.
AB  - Despite extensive use, to the best of our knowledge, no trial has simultaneously
      compared the three currently used erythropoietin-stimulating agents (ESAs) in a
      prospective manner in the treatment of anemia of end-stage renal disease
      patients. All hemodialysis patients in Qatar who were treated with short-acting
      epoetin alfa or beta have been screened. Eligible patients had been prospectively
      randomized, either to continue on the previous regimen of epoetin or to receive
      darbepoetin alfa or continuous erythropoietin receptor activator (CERA) for a
      total period of 40 weeks. All groups were assessed at the end of the study for
      safety and efficacy parameters. A total of 327 eligible patients were randomized.
      Mean hemoglobin concentration remained constant within the recommended target
      range (11-12 g/dL) throughout the study in the three studied groups. The
      percentage of patients who reached the target range was constantly above 50% in
      the second half of the study among CERA group patients who also had significantly
      lower mean number of dose adjustments as compared with the other two groups (P =
      0.001). Similarly, the number of discontinuations of ESA among epoetin,
      darbepoetin, and CERA groups was 17, 19, and 9, respectively (P = 0.042). The
      frequencies of adverse events were similar in all groups. This study has
      specifically compared the effect of ESA type on the variability of serum
      hemoglobin levels in hemodialysis patients. Furthermore, it confirmed the
      efficacy and safety of once monthly CERA for maintaining tight hemoglobin control
      within recommended target ranges.

PMID- 24894342
TI  - Dietary fat intake in relation to lethal breast cancer in two large prospective
      cohort studies.
AB  - Whether fat intake influences risk of developing more aggressive, lethal breast
      tumors is unknown. We evaluated intakes of total fat, specific types of fat, and
      cholesterol prior to diagnosis in relation to lethal breast cancer risk in 88,759
      women in the Nurses' Health Study (NHS; 1980-2010) and 93,912 women in the
      Nurses' Health Study II (NHSII; 1991-2010). Diet was assessed every 4 years using
      a semi-quantitative food frequency questionnaire. Breast cancers were confirmed
      with pathology reports; deaths were confirmed by next of kin or the National
      Death Index. We defined lethal cases as women with invasive breast cancer who
      died of breast cancer. We pooled the cohorts and used multivariable Cox
      proportional hazards models. We identified 1,529 lethal breast cancer cases
      (1,279 in NHS and 250 in NHSII). Higher total fat intake was associated with a
      slightly lower lethal breast cancer risk (top vs. bottom quintile hazard ratio
      [HR] 0.85; 95 % CI 0.72, 1.01; p trend = 0.05). Specific types of fat were
      generally not associated with lethal breast cancer risk. For example, compared
      with those in the lowest quintile of saturated fat intake, those in the highest
      quintile had a HR of 0.98 (95 % CI 0.75, 1.26; p trend = 0.96). Among women
      diagnosed with breast cancer, pre-diagnosis fat intake was not associated with
      survival. Higher pre-diagnosis fat intake was not associated with greater risk of
      lethal breast cancer in these large prospective cohort studies, consistent with
      the weight of the evidence against a causal role for fat intake and breast cancer
      incidence.

PMID- 24894345
TI  - Predictive spatial risk model of poliovirus to aid prioritization and hasten
      eradication in Nigeria.
AB  - BACKGROUND: One of the challenges facing the Global Polio Eradication Initiative
      is efficiently directing limited resources, such as specially trained personnel,
      community outreach activities, and satellite vaccinator tracking, to the most at
      risk areas to maximize the impact of interventions. A validated predictive model
      of wild poliovirus circulation would greatly inform prioritization efforts by
      accurately forecasting areas at greatest risk, thus enabling the greatest effect
      of program interventions. METHODS: Using Nigerian acute flaccid paralysis
      surveillance data from 2004-2013, we developed a spatial hierarchical Poisson
      hurdle model fitted within a Bayesian framework to study historical polio
      caseload patterns and forecast future circulation of type 1 and 3 wild poliovirus
      within districts in Nigeria. A Bayesian temporal smoothing model was applied to
      address data sparsity underlying estimates of covariates at the district level.
      RESULTS: We find that calculated vaccine-derived population immunity is
      significantly negatively associated with the probability and number of wild
      poliovirus case(s) within a district. Recent case information is significantly
      positively associated with probability of a case, but not the number of cases. We
      used lagged indicators and coefficients from the fitted models to forecast
      reported cases in the subsequent six-month periods. Over the past three years,
      the average predictive ability is 86 +/- 2% and 85 +/- 4% for wild poliovirus
      type 1 and 3, respectively. Interestingly, the predictive accuracy of historical
      transmission patterns alone is equivalent (86 +/- 2% and 84 +/- 4% for type 1 and
      3, respectively). We calculate uncertainty in risk ranking to inform assessments
      of changes in rank between time periods. CONCLUSIONS: The model developed in this
      study successfully predicts districts at risk for future wild poliovirus cases in
      Nigeria. The highest predicted district risk was 12.8 WPV1 cases in 2006, while
      the lowest district risk was 0.001 WPV1 cases in 2013. Model results have been
      used to direct the allocation of many different interventions, including
      political and religious advocacy visits. This modeling approach could be applied
      to other vaccine preventable diseases for use in other control and elimination
      programs.

PMID- 24894348
TI  - Storage of volume-reduced washed platelets in M-sol additive solution for 7 days.
AB  - BACKGROUND: Volume-reduced washed platelets (VR-wPLTs), which are prepared by
      concentrating platelets (PLTs) into a smaller volume of additive solution (AS),
      may prevent not only circulatory overload, but also adverse reactions caused by
      plasma components. Although VR-wPLTs may be quickly degraded due to high PLT
      concentrations, few studies have examined the effects of storage on VR-wPLTs. We
      examined here the in vitro properties of VR-wPLTs prepared with M-sol AS during
      their storage for 7 days. STUDY DESIGN AND METHODS: Platelet concentrates (PCs)
      were divided into two equal aliquots (control group and test group). After the
      centrifugation of both aliquots and removal of as much supernatant as possible,
      the pellet of the control group was resuspended in 160 mL of M-sol while that of
      the test group was resuspended in 80 or 40 mL of M-sol. The wPLTs of both groups
      were stored in polyolefin bags with agitation at 20 to 24 degrees C for 7 days.
      RESULTS: The pH values of both groups were maintained at higher than 7.0 during
      the 7-day storage. Differences in %disk, CD62P, annexin V, percent hypotonic
      shock response, and aggregation values between the test group and control group
      were small for at least 2 days after washing. CONCLUSIONS: The in vitro
      properties of VR-wPLTs were not markedly degraded for at least 2 days. Therefore,
      the storage properties of PLTs may be maintained in VR-wPLTs prepared at blood
      centers until they are administered to patients in hospitals.

PMID- 24894347
TI  - Is preoperative radiation therapy as effective as postoperative radiation therapy
      for heterotopic ossification prevention in acetabular fractures?
AB  - BACKGROUND: Prophylactic approaches to prevent heterotopic ossification after
      acetabular fracture surgery have included indomethacin and/or single-dose
      external beam radiation therapy administered after surgery. Although preoperative
      radiation has been used for heterotopic ossification prophylaxis in the THA
      population, to our knowledge, no studies have compared preoperative and
      postoperative radiation therapy in the acetabular fracture population.
      QUESTIONS/PURPOSES: We determined whether heterotopic ossification frequency and
      severity were different between patients with acetabular fracture treated with
      prophylactic radiation therapy preoperatively and postoperatively. METHODS:
      Between January 2002 and December 2009, we treated 320 patients with a Kocher
      Langenbeck approach for acetabular fractures, of whom 50 (34%) were treated with
      radiation therapy preoperatively and 96 (66%) postoperatively. Thirty-four (68%)
      and 71 (74%), respectively, had 6-month radiographs available for review and were
      included. For hospital logistical reasons, patients who underwent operative
      treatment on a Friday or Saturday received radiation therapy preoperatively, and
      all others received it postoperatively. The treatment groups were comparable in
      terms of most demographic parameters, injury severity, and fracture patterns. Six
      month postoperative radiographs were reviewed and graded according to Brooker.
      Followup ranged from 6 to 93 months and 6 to 97 months for the preoperative and
      postoperative groups, respectively. Post hoc power analysis showed our study was
      powered to detect a difference of 22% or more between patients with severe
      heterotopic ossification. Sample size calculations showed 915 subjects would be
      needed to detect a 5% relative difference in severe heterotopic ossification
      status between groups. RESULTS: We detected no difference in heterotopic
      ossification frequency between the preoperative (eight of 36, 22%) and
      postoperative (19 of 71, 27%) groups (p=0.609). There was also no difference in
      heterotopic ossification severity between groups (p=0.666). Two of 36 (6%) in the
      preoperative group and three of 71 (4%) in the postoperative group developed
      clinically significant Grade III heterotopic ossification. No patients developed
      Grade IV heterotopic ossification. CONCLUSIONS: We found no difference in
      heterotopic ossification frequency or severity when comparing preoperative and
      postoperative radiation therapy. However, given the relatively low frequency of
      heterotopic ossification in this population, in particular the frequency of
      severe or symptomatic heterotopic ossification, the possibility of a Type II
      error must be considered. Larger, prospective studies are required to confirm our
      no-difference finding, but insofar as the result in this fracture population
      mirrors that of the THA population, unless our finding is disproven, we believe
      radiation therapy can be given either before or after surgery, as dictated by the
      clinical scenario. LEVEL OF EVIDENCE: Level III, therapeutic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24894349
TI  - In situ oxidation study of Pd-Rh nanoparticles on MgAl2O4(001).
AB  - Alloy nanoparticles on oxide supports are widely used as heterogeneous catalysts
      in reactions involving oxygen. Here we discuss the oxidation behavior of Pd-Rh
      alloy nanoparticles on MgAl2O4(001) supports with a particle diameter from 6-11
      nm. As an In situ tool, we employed high energy grazing incidence X-ray
      diffraction at a photon energy of 85 keV. We find that physical vapor deposited
      Pd-Rh nanoparticles grow epitaxially on MgAl2O4(001) with a truncated octahedral
      shape over the whole concentration range. During our systematic oxidation
      experiments performed at 670 K in the pressure range from 10(-3) to 0.1 mbar, we
      observe for Rh containing nanoparticles the formation of two different Rh oxide
      phases, namely RhO2 and a spinel-like Rh3O4 phase. PdO formation is only observed
      for pure Pd nanoparticles. This oxidation induced segregation behavior is also
      reflected in the oxidation induced enlargement of the average nanoparticle
      lattice parameter towards to value for pure Pd. Our results have ramifications
      for the phase separation behavior of alloy nanocatalysts under varying reducing
      and oxidizing environments. 

PMID- 24894350
TI  - Lipid is moving to the forefront of bio-medical research.

PMID- 24894351
TI  - Diurnal regulation of lipid metabolism and applications of circadian lipidomics.
AB  - The circadian timing system plays a key role in orchestrating lipid metabolism.
      In concert with the solar cycle, the circadian system ensures that daily rhythms
      in lipid absorption, storage, and transport are temporally coordinated with rest
      activity and feeding cycles. At the cellular level, genes involved in lipid
      synthesis and fatty acid oxidation are rhythmically activated and repressed by
      core clock proteins in a tissue-specific manner. Consequently, loss of clock gene
      function or misalignment of circadian rhythms with feeding cycles (e.g., in shift
      work) results in impaired lipid homeostasis. Herein, we review recent progress in
      circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid
      metabolites, to characterize circadian-regulated lipid pathways in mammals. In
      mice, novel regulatory circuits involved in fatty acid metabolism have been
      identified in adipose tissue, liver, and muscle. Extensive diversity in circadian
      regulation of plasma lipids has also been revealed in humans using lipidomics and
      other metabolomics approaches. In future studies, lipidomics platforms will be
      increasingly used to better understand the effects of genetic variation, shift
      work, food intake, and drugs on circadian-regulated lipid pathways and metabolic
      health. 

PMID- 24894352
TI  - Recent advances in understanding proteins involved in lipid droplet formation,
      growth and fusion.
AB  - Lipid droplets (LDs) were once viewed as simple, inert lipid micelles. However,
      they are now known to be organelles with a rich proteome involved in a myriad of
      cellular processes. LDs are heterogeneous in nature with different sizes and
      compositions of phospholipids, neutral lipids and proteins. This review takes a
      focused look at the roles of proteins involved in the regulation of LD formation,
      expansion, and morphology. The related proteins are summarized such as the fat
      specific protein (Fsp27), fat storage-inducing transmembrane (FIT) proteins,
      seipin and ADP-ribosylation factor 1-coat protein complex I (Arf-COPI). Finally,
      we present important challenges in LD biology for a deeper understanding of this
      dynamic organelle to be achieved. 

PMID- 24894353
TI  - The involvement of lipids in Alzheimer's disease.
AB  - It has been estimated that Alzheimer's disease (AD), the most common form of
      dementia, will affect approximately 81 million individuals by 2040. To date, the
      actual cause and cascade of events in the progression of this disease have not
      been fully determined. Furthermore, there is currently no definitive blood test
      or simple diagnostic method for AD. Considerable efforts have been put into
      proteomic approaches to develop a diagnostic blood test, but to date these
      efforts have not been successful. More recently, there has been a stronger focus
      on lipidomic studies in the hope of increasing our understanding of the
      underlying mechanisms leading to AD and developing an AD blood test. It is well
      known that the strongest genetic risk factor for AD is the epsilon4 variant of
      apolipoprotein E (APOE). Evidence suggests that the ApoE protein, a major lipid
      transporter, plays a key role in the pathogenesis of AD, and its role in both
      normal and aberrant lipid metabolism warrants further extensive investigation.
      Here, we review ApoE-lipid interactions, as well as the roles that lipids may
      play in the pathogenesis of AD. 

PMID- 24894354
TI  - A lipidomic perspective on intermediates in cholesterol synthesis as indicators
      of disease status.
AB  - Lipidomics is increasingly becoming a viable method for researchers to routinely
      identify the various sterols present in samples, beyond just measuring
      cholesterol itself. In particular, the measurement of intermediates in
      cholesterol synthesis can shed new insights into not only the flux through the
      pathway, but also numerous disease states where levels of sterol intermediates
      are drastically altered. In this review, we indicate several intermediates that
      are relevant to disease, and discuss the challenges for analysing them, including
      the need for standardised methodology or universal controls across the lipidomics
      field. 

PMID- 24894355
TI  - Galphaq, Ggamma1 and Plc21C control Drosophila body fat storage.
AB  - Adaptive mobilization of body fat is essential for energy homeostasis in animals.
      In insects, the adipokinetic hormone (Akh) systemically controls body fat
      mobilization. Biochemical evidence supports that Akh signals via a G protein
      coupled receptor (GPCR) called Akh receptor (AkhR) using cyclic-AMP (cAMP) and
      Ca(2+) second messengers to induce storage lipid release from fat body cells.
      Recently, we provided genetic evidence that the intracellular calcium (iCa(2+))
      level in fat storage cells controls adiposity in the fruit fly Drosophila
      melanogaster. However, little is known about the genes, which mediate Akh
      signalling downstream of the AkhR to regulate changes in iCa(2+). Here, we used
      thermogenetics to provide in vivo evidence that the GPCR signal transducers G
      protein alpha q subunit (Galphaq), G protein gamma1 (Ggamma1) and Phospholipase C
      at 21C (Plc21C) control cellular and organismal fat storage in Drosophila.
      Transgenic modulation of Galphaq, Ggamma1 and Plc21C affected the iCa(2+) of fat
      body cells and the expression profile of the lipid metabolism effector genes
      midway and brummer, which results in severely obese or lean flies. Moreover,
      functional impairment of Galphaq, Ggamma1 and Plc21C antagonised Akh-induced fat
      depletion. This study characterizes Galphaq, Ggamma1 and Plc21C as anti-obesity
      genes and supports the model that Akh employs the Galphaq/Ggamma1/Plc21C module
      of iCa(2+) control to regulate lipid mobilization in adult Drosophila. 

PMID- 24894356
TI  - Comprehensive analysis of lipid composition in crude palm oil using multiple
      lipidomic approaches.
AB  - Palm oil is currently the leading edible oil consumed worldwide. Triacylglycerol
      (TAG) and diacylglycerol (DAG) are the dominant lipid classes in palm oil. Other
      lipid classes present in crude palm oil, such as phospholipids and galactolipids,
      are very low in abundance. These low-abundance lipids constitute key
      intermediates in lipid biosynthesis. In this study, we applied multiple lipidomic
      approaches, including high-sensitivity and high-specificity multiple reaction
      monitoring, to comprehensively quantify individual lipid species in crude palm
      oil. We also established a new liquid chromatography-coupled mass spectrometry
      method that allows direct quantification of low-abundance galactolipids in palm
      oil without the need for sample pretreatment. As crude palm oil contains large
      amounts of neutral lipids, our direct-detection method circumvents many of the
      challenges encountered with conventional lipid quantification methods. This
      approach allows direct measurement of lipids with no hassle during sample
      preparation and is more accurate and precise compared with other methods.

PMID- 24894357
TI  - A lipid droplet-associated GFP reporter-based screen identifies new fat storage
      regulators in C. elegans.
AB  - Fat storage disorders including obesity are pandemic human health problems. As a
      genetically amenable model organism, Caenorhabditis elegans has often been used
      to explore the molecular mechanisms of fat storage regulation. Dye staining of
      fixed animals and stimulated Raman scattering (SRS) microscopy methods have been
      used successfully to study fat storage, but a genetic screening system that takes
      full advantage of C. elegans transparency to perform live imaging of fluorescent
      protein reporters has not yet been reported. Here, we investigated the tissue
      specific expression of the GFP fusion of Perilipin 1 (PLIN1), a Drosophila lipid
      droplet-associated protein, in C. elegans. Our results indicate that PLIN1::GFP
      labels lipid droplets and can be used as a fat storage indicator in live worms.
      Through an RNAi screen, we further identified several previously uncharacterized
      new fat storage regulators. 

PMID- 24894360
TI  - Abstracts of the 30(th) Annual Scientific Meeting of the Australasian College for
      Emergency Medicine, 24-28 November 2013, Adelaide, Australia.

PMID- 24894359
TI  - School-readiness profiles of children with language impairment: linkages to home
      and classroom experiences.
AB  - BACKGROUND: This study represents an effort to advance our understanding of the
      nature of school readiness among children with language impairment (LI), a
      population of children acknowledged to be at risk of poor academic achievement.
      The academic, social-emotional, and behavioural competencies with which children
      arrive at kindergarten affect the nature of their future educational experiences,
      and their overall academic achievement. AIMS: To examine whether there are
      reliable profiles that characterize children with LI just prior to kindergarten
      entrance, and the extent to which profile membership is associated with
      characteristics of children's homes and preschool experiences. Questions
      addressed were twofold: (1) To what extent are there reliable profiles of
      children with LI with respect to their school readiness? (2) To what extent is
      children's profile membership associated with characteristics of their homes and
      preschool classrooms? METHODS & PROCEDURES: Participants were 136 children with
      LI from early childhood special education classrooms. We utilized latent class
      analysis (LCA) to classify individuals into profiles based on individual
      responses on school readiness measures. We then used multilevel hierarchical
      generalized linear models to examine the relations between profile membership and
      children's home/classroom experiences. OUTCOMES & RESULTS: LCA analyses revealed
      that a four-profile solution was the most appropriate fit for the data and that
      classroom experiences were predictive of these profiles, such that children in
      classrooms with more instructional/emotional support were more likely to be
      placed in profiles characterized by higher school readiness skills. CONCLUSIONS &
      IMPLICATIONS: These results suggest that the school readiness profiles of young
      children with LI are associated with the quality of children's classroom
      experiences, and that high-quality classroom experiences can be influential for
      ensuring that young children with LI arrive in kindergarten ready to learn.

PMID- 24894358
TI  - Serum biomarkers predictive of cure in Chagas disease patients after nifurtimox
      treatment.
AB  - BACKGROUND: Chagas disease (CD), caused by the protozoan Trypanosoma cruzi,
      remains an important public health issue in many Central and South American
      countries, as well as non-endemic areas with high rates of immigration from these
      countries. Existing treatment options for CD are limited and often
      unsatisfactory. Moreover the lack of post-treatment tests of cure limits the
      development of new drugs. To address this issue, we sought to identify serum
      biomarkers following nifurtimox (Nfx) treatment that could be used as an early
      test of cure and/or markers of a therapeutic response. METHODS: Human sera from
      Chagas patients pre- and post-treatment with Nfx (n = 37) were compared to
      samples from healthy subjects (n = 37) using a range of proteomic and immunologic
      techniques. Biomarker peaks with the best discriminatory power were further
      characterized. RESULTS: Using serum samples (n = 111), we validated the presence
      of five key biomarkers identified in our previous study, namely human
      apolipoprotein A-I (APOA1) and specific fragments thereof and one fragment of
      human fibronectin (FN1). In chagasic serum samples all biomarkers except full
      length APOA1 were upregulated. These five biomarkers returned to normal in 43%
      (16/37) of the patients treated with Nfx at three years after treatment.
      CONCLUSIONS: The normalization of biomarker patterns strongly associated with CD
      suggests that these markers can be used to identify patients in whom Nfx
      treatment is successful. We believe that these are the first biomarkers
      predictive of cure in CD patients.

PMID- 24894361
TI  - A novel method for non-invasive plaque morphology analysis by coronary computed
      tomography angiography.
AB  - Coronary computed tomography angiography (CCTA) plaque morphology based on
      conventional Hounsfield units relies on absolute CT numbers is influenced by
      imaging and anatomical variables. The project describes and tests a novel
      alternative method, termed the "labeling method", which uses relative CT numbers
      and 3-dimensional plaque structure. Using virtual histology intravascular
      ultrasound (VH-IVUS) as the reference standard, this study compares the labeling
      method to a conventional CT-number based method to determine coronary plaque
      morphology. Thirty-seven high-risk, non-calcified atherosclerotic coronary
      lesions were prospectively evaluated in 33 consecutive patients who underwent
      CCTA followed by VH-IVUS (mean interval 8.6 +/- 13.3 days). CCTA-derived vessel
      and minimum lumen areas were compared to VH-IVUS measures. Fibrotic and necrotic
      core areas were calculated by both the labeling method to the CT-number based
      method; both were tested for agreement with reference standard VH-IVUS. Inter-
      and intra-observer correlations were assessed. CCTA significantly underestimated
      minimum lumen area when compared to VH-IVUS (mean difference -1.4 +/- 0.9 mm(2),
      p < 0.0001). Necrotic core and fibrous areas quantified using the labeling method
      demonstrated superior correlation with VH-IVUS compared to those quantified using
      the CT-number based method, Pearson's r = 0.75 versus 0.42 and r = 0.80 and 0.59,
      respectively. Compared to VH-IVUS, limits of agreement for the labeling method
      derived necrotic core (-2.0 to 2.5 mm(2)) and fibrous areas (0.6-8.0 mm(2)) were
      more narrow than those determined using the CT-number based method (-3.7 to 7.3
      and -4.0 to 8.9 mm(2), respectively). Inter- and intraobserver correlations were
      excellent for all CCTA derived measures (r = 0.85-0.98). A novel CCTA-based
      labeling method offers an alternative to conventional CT-number based analyses
      for plaque morphology. The labeling method demonstrates superior correlation to
      VH-IVUS for measures of fibrotic and necrotic core areas within non-calcified
      coronary atherosclerotic plaques.

PMID- 24894362
TI  - Screening for potential co-products in a Miscanthus sinensis mapping family by
      liquid chromatography with mass spectrometry detection.
AB  - Society is demanding more green chemicals from sustainable sources. Miscanthus is
      a potential source of platform chemicals and bioethanol through fermentation.
      Miscanthus sinensis (M. sinensis) has been found to contain particularly high
      levels of soluble phenols (hydroxycinnamates and flavonoids) which may have
      application in the nutraceutical, cosmetic and pharmaceutical industries. Here,
      we describe the first study on the identification and quantification of phenols
      from the leaf tissue of a bi-parental M. sinensis mapping family. Parents and
      progeny showed complex profiles of phenols with highly related structures which
      complicated characterisation of individual phenotypes. Separation of semi
      purified extracts by reverse-phase liquid chromatography, coupled with detection
      by diode array and ESI-MS/MS, enabled distinction of different profiles of
      phenols. Ten hydroxycinnamates (O-cinnamoylquinic acids) and several flavones
      (one mono-O-glycosyl flavone, eight mono-C-glycosyl flavones, two di-C-glycosyl
      flavones, five O-glycosyl-C-glycosyl flavones and nine 2"-O-glycosyl-C-glycosyl
      flavones) were identified and quantified in leaf tissue of two hundred progeny
      and maternal and paternal plants during the seedling stage. Progeny exhibiting
      high, moderate and low amounts of hydroxycinnamates and flavonoids and both
      parents were selected and screened at seven months' growth to determine the
      abundance of these phenols at their highest biomass and compared with seedlings.
      Concentrations of phenols generally decreased as leaves matured. Several flavone
      glycosides were identified. This technique can be used for rapid screening of
      plants in a mapping family to identify genotypes with high phenol content to add
      value in the biorefinery chain. This comparative study provides information on
      the content of potentially valuable compounds from readily renewable resources
      and possible biomarkers for identification in breeding programmes. 

PMID- 24894364
TI  - Putative inhibitory training of a stimulus makes it a facilitator: a within
      subject comparison of visual and auditory stimuli in autoshaping.
AB  - Pigeons were trained with the A+, AB-, ABC+, AD- and ADE+ task where each of
      stimulus A and stimulus compounds ABC and ADE signalled food (positive trials),
      and each of stimulus compounds AB and AD signalled no food (negative trials).
      Stimuli A, B, C and E were small visual figures localised on a response key, and
      stimulus D was a white noise. Stimulus B was more effective than D as an
      inhibitor of responding to A during the training. After the birds learned to
      respond exclusively on the positive trials, effects of B and D on responding to C
      and E, respectively, were tested by comparing C, BC, E and DE trials. Stimulus B
      continuously facilitated responding to C on the BC test trials, but D's
      facilitative effect was observed only on the first DE test trial. Stimulus B also
      facilitated responding to E on BE test trials. Implications for the Rescorla
      Wagner elemental model and the Pearce configural model of Pavlovian conditioning
      were discussed. 

PMID- 24894363
TI  - Optimizing isolation culture and freezing methods to preserve Wharton's jelly's
      mesenchymal stem cell (MSC) properties: an MSC banking protocol validation for
      the Hellenic Cord Blood Bank.
AB  - BACKGROUND: Mesenchymal stem or stromal cells (MSCs) are a heterogeneous
      population that can be isolated from many tissues including umbilical cord
      Wharton's jelly (UC-WJ). Although initially limited in studies such as a
      hematopoietic stem cell transplantation adjuvant, an increasing number of
      clinical trials consider MSCs as a potential anti-inflammatory or a regenerative
      medicine agent. It has been proposed that creating a repository of MSCs would
      increase their availability for clinical applications. The aim of this study was
      to assess the optimal isolation and cryopreservation procedures to facilitate WJ
      MSC banking. STUDY DESIGN AND METHODS: Cells were isolated from UC-WJ using
      enzymatic digestion or plastic adhesion methods. Their isolation efficacy, growth
      kinetics, immunophenotype, and differentiation potential were studied, as well as
      the effects of freezing. Flow cytometry for common MSC markers was performed on
      all cases and differentiation was shown with histocytochemical staining. Finally,
      the isolation efficacy on cryopreserved WJ tissue fragments was tested. RESULTS:
      MSC isolation was successful using both isolation methods on fresh UC-WJ tissue.
      However, UC-WJ MSC isolation from frozen tissue fragments was impossible. Flow
      cytometry analysis revealed that only MSC markers were expressed on the surface
      of the isolated cells while differentiation assays showed that they were capable
      of trilinear differentiation. All the above characteristics were also preserved
      in isolated UC-WJ MSCs over the cryopreservation study period. CONCLUSION: These
      data showed that viable MSCs can only be isolated from fresh UC-WJ tissue,
      setting the foundation for clinical-grade banking.

PMID- 24894365
TI  - Response thresholds to recruitment signals and the regulation of foraging
      intensity in the ant Myrmica sabuleti (Hymenoptera, Formicidae).
AB  - The optimal foraging theory predicts that colonies of social insects must be able
      to adjust the intensity of their foraging behaviour as a function of the quality
      of the food discovered. Here, the mechanisms allowing the regulation of
      recruitment as a function of food concentration in the ant Myrmica sabuleti were
      analyzed. Although the total number of foragers engaged in food collection during
      recruitments increased with increasing concentration of sucrose solutions (0.1
      vs. 1 M), neither the proportion of recruiting scouts nor the invitation
      behaviour performed by the scouts in the nest can explain this relationship.
      Foragers trail more when coming back from a 1 M than from a 0.1 M sucrose
      solution. However, this alone cannot explain the collective patterns observed
      since the mean numbers of workers leaving the nest after the entry of a scout
      coming back from either 0.1 or 1 M sources were not significantly different. We
      suggest that a spatial distribution of the foragers in the nest as a function of
      their motivational state could be part of the regulation process. The ants
      located near the nest entrance would respond to both low and high trail pheromone
      signals, but those located deeper in the nest would respond only to high level
      signals, resulting in higher recruitment rate towards richer sources. 

PMID- 24894366
TI  - Factors affecting context specificity of appetitive conditioned responding.
AB  - The present experiment contributes to the identification of factors affecting
      magnitude of context specificity of simple appetitive conditioned responding.
      Rats were first trained to associate an auditory and a visual stimulus with food.
      Each of these stimuli was consistently presented in a distinctive environmental
      context. Groups of rats differed only in the number of conditioning trials. At
      test, all groups received trials on which each of the stimuli was presented
      either in the same context as used during training, or in the different context.
      Rats made significantly fewer food-magazine visits on different-context trials
      than on same-context trials only under the conditions that the stimulus tested
      was the auditory stimulus, which generally elicited a stronger conditioned
      response (CR) than did the visual stimulus, and the animals had received a
      relatively small number of conditioning trials. Apparently, magnitude of context
      specificity is affected by factors determining the strength of the appetitive
      conditioned response to the target stimulus. 

PMID- 24894367
TI  - Formation of a novel preference and aversion by simultaneous activation of the
      representations of absent cues.
AB  - Pairing the associatively activated representation of almond with the
      representation of sucrose resulted in greater consumption of almond on test than
      controls. In addition, pairing the representation of almond with the
      representation of quinine resulted in lower almond consumption than controls.
      These results support and extend the novel finding of Dwyer, Mackintosh and
      Boakes [Dwyer, D.M., Mackintosh, N.J., Boakes, R.A., 1998. Simultaneous
      activation of the representation of absent cues results in the formation of an
      excitatory association between them. J. Exp. Psychol. Anim. Behav. Process. 24,
      163-171] that a preference could be established to a neutral flavour by pairing
      the representation of that flavour with the representation of sucrose in the
      absence of either flavour. Taken together these results question the modification
      of SOP proposed by Holland [Holland, P.C., 1983. Representation mediated
      overshadowing and potentiation of conditioned aversions. J. Exp. Psychol. Anim.
      Behav. Process. 9, 1-13; Holland, P.C., 1990. Event representation in Pavlovian
      conditioning: image and action. Cognition 37, 105-131] to explain the occurrence
      of mediated conditioning. An alternative modification of SOP by Dickinson and
      Burke [Dickinson, A., Burke, J., 1996. Within-compound associations mediate the
      retrospective revaluation of causality judgments. Q. J. Exp. Psychol. 49B, 60-80]
      is considered, but while it can account for the current results it does not
      predict mediated conditioning. 

PMID- 24894368
TI  - The role of fear in one-trial passive avoidance learning in Japanese quail chicks
      genetically selected for long or short duration of the tonic immobility reaction.
AB  - Emotional arousal has been shown to affect learning in mammals, but little is
      known about the relationship between fear and learning in birds. In order to
      investigate this relationship, the learning abilities of Japanese quail chicks
      from lines that have been divergently selected for high or low levels of
      underlying fearfulness, as measured by the duration of tonic immobility
      behaviour, were compared. Day-old chicks from both lines were trained in a one
      trial passive avoidance task. In this task, young chicks spontaneously peck at a
      small, visually conspicuous bead. If the bead has been coated with a gustatory
      aversant, the chicks learn in a single trial not to peck a similar, uncoated bead
      upon subsequent presentation. Significantly more chicks of the low fear line
      pecked the training bead compared to those of the high fear line. However, 2 h
      later, chicks of both lines trained on a methyl anthranilate-coated bead showed
      similar avoidance of the test bead. Therefore, although fear affected performance
      during training, it did not appear to directly affect memory formation in this
      task. 

PMID- 24894369
TI  - Effect of group disruption on social behaviour in lines of Japanese quail
      (Coturnixjaponica) selected for high or low levels of social reinstatement
      behaviour.
AB  - Japanese quail of lines selected for high (HSR) or low (LSR) levels of social
      reinstatement (SR) behaviour were reared in groups of three. At 3 and 6 weeks of
      age, one group member was replaced with an unfamiliar conspecific bird. Behaviour
      following introduction of the intruder was similar at both ages. Quail of both
      lines spent more time immobile after introduction of the intruder than before its
      introduction. In the LSR, but not the HSR line, inter-individual distances
      between intruders and other chicks, were greater than those between familiar
      chicks. Birds of both lines pecked more between unfamiliar than between familiar
      birds. Pecks, not associated with escape or avoidance by the pecked bird, were
      more frequent in HSR groups. Selection for HSR behaviour appears to have
      increased non-aggressive exploration of intruder whereas selection for LSR
      behaviour has decreased interest in or increased shunning of intruders. 

PMID- 24894370
TI  - Oxidative stress in relation to reproduction, contaminants, gender and age in a
      long-lived seabird.
AB  - Reproduction is a demanding activity for animals, since they must produce, and in
      some cases protect and provision, their young. It is often overlooked that
      demands of reproduction may also be exacerbated by exposure to contaminants. In
      this study, we make use of an exceptional long-term dataset to perform a cross
      sectional study on the long-lived wandering albatross (Diomedea exulans) in order
      to test the effects of reproduction, persistent organic pollutants [POPs:
      pesticides and polychlorinated biphenyls (PCBs)], mercury, individual age (3-47
      years), and sex on the levels of plasma oxidative damage and inflammation. The
      results of our study support the hypothesis that oxidative damage may be a
      physiological cost of reproduction and that individuals carrying higher levels of
      organic or non-organic contaminants have higher oxidative damage. Levels of the
      inflammatory protein haptoglobin were similar between breeding and non-breeding
      birds, with the exception of breeding males which had the lowest levels of
      haptoglobin. Our data also show an effect of age and of organic contaminants on
      the plasma oxidative damage level, but not on plasma haptoglobin. In addition,
      plasma oxidative damage level increased with red blood cell mercury concentration
      in females but not in males. Hence, our study highlights that the harmful effects
      of contaminants may come through interaction with factors like life stage or
      gender, suggesting potential for high variation in susceptibility to
      contamination among individuals.

PMID- 24894372
TI  - Simulation of Cross-border Impacts Resulting from Classical Swine Fever Epidemics
      within the Netherlands and Germany.
AB  - The cross-border region of the Netherlands (NL) and the two German states of
      North Rhine Westphalia (NRW) and Lower Saxony (LS) is a large and highly
      integrated livestock production area. This region increasingly develops towards a
      single epidemiological area in which disease introduction is a shared veterinary
      and, consequently, economic risk. The objectives of this study were to examine
      classical swine fever (CSF) control strategies' veterinary and direct economic
      impacts for NL, NRW and LS given the current production structure and to analyse
      CSF's cross-border causes and impacts within the NL-NRW-LS region. The course of
      the epidemic was simulated by the use of InterSpread Plus, whereas economic
      analysis was restricted to calculating disease control costs and costs directly
      resulting from the control measures applied. Three veterinary control strategies
      were considered: a strategy based on the minimum EU requirements, a vaccination
      and a depopulation strategy based on NL and GER's contingency plans. Regardless
      of the veterinary control strategy, simulated outbreak sizes and durations for
      2010 were much smaller than those simulated previously, using data from over 10
      years ago. For example, worst-case outbreaks (50th percentile) in NL resulted in
      30-40 infected farms and lasted for two to four and a half months; associated
      direct costs and direct consequential costs ranged from ?24.7 to 28.6 million and
      ?11.7 to 26.7 million, respectively. Both vaccination and depopulation strategies
      were efficient in controlling outbreaks, especially large outbreaks, whereas the
      EU minimum strategy was especially deficient in controlling worst-case outbreaks.
      Both vaccination and depopulation strategies resulted in low direct costs and
      direct consequential costs. The probability of cross-border disease spread was
      relatively low, and cross-border spread resulted in small, short outbreaks in
      neighbouring countries. Few opportunities for further cross-border harmonization
      and collaboration were identified, including the implementation of cross-border
      regions (free and diseased regions regardless of the border) in case of outbreaks
      within close proximity of the border, and more and quicker sharing of information
      across the border. It was expected, however, that collaboration to mitigate the
      market effects of an epidemic will create more opportunities to lower the impact
      of CSF outbreaks in a cross-border context.

PMID- 24894371
TI  - Competing neighbors: light perception and root function.
AB  - Plant responses to competition have often been described as passive consequences
      of reduced resource availability. However, plants have mechanisms to forage for
      favorable conditions and anticipate competition scenarios. Despite the progresses
      made in understanding the role of light signaling in modulating plant-plant
      interactions, little is known about how plants use and integrate information
      gathered by their photoreceptors aboveground to regulate performance belowground.
      Given that the phytochrome family of photoreceptors plays a key role in the
      acquisition of information about the proximity of neighbors and canopy cover, it
      is tempting to speculate that changes in the red:far-red (R:FR) ratio perceived
      by aboveground plant parts have important implications shaping plant behavior
      belowground. Exploring data from published experiments, we assess the neglected
      role of light signaling in the control of root function. The available evidence
      indicates that plant exposure to low R:FR ratios affects root growth and
      morphology, root exudate profiles, and interactions with beneficial soil
      microorganisms. Although dependent on species identity, signals perceived
      aboveground are likely to affect root-to-root interactions. Root systems could
      also be guided to deploy new growth predominantly in open areas by light signals
      perceived by the shoots. Studying interactions between above- and belowground
      plant-plant signaling is expected to improve our understanding of the mechanisms
      of plant competition. 

PMID- 24894374
TI  - Strategies for reliable and improved large-scale production of Pyrococcus
      furiosus with integrated purification of hydrogenase I.
AB  - The hyperthermophilic archaeon Pyrococcus furiosus is an interesting organism for
      research and application, especially owing to its unique NADPH-dependent
      hydrogenase I. However, mass production of P. furiosus through fermentation is
      susceptible to fault because of its sensitivity to oxygen, a short exponential
      and stationary phase and a rapid cell lysis in typical cultivation process. In
      this study, significant improvement for pilot plant scale production processes
      for P. furiosus biomass was made by investigations of the fermentation process
      with subsequent hydrogenase I enzyme purification. Scale-up in a 300-L stirred
      tank bioreactor was successfully achieved. A repeated-batch cultivation process
      with high reproducibility and productivity was realized. Furthermore, the enzyme
      hydrogenase I was purified, and its activity tested and verified. The
      improvements in this production process for the production of large amount of P.
      furiosus biomass and hydrogenase I have been achieved, especially by successfully
      implementing the following key measures and steps: unsterile cultivation setup,
      skipping typical intermediate preculture and inoculation steps, accelerating the
      cultivation process by defining an optimal state of the inoculation, optimal time
      point of biomass harvesting and finally by choosing a one-step purification
      procedure for enzyme recovery. 

PMID- 24894373
TI  - In vitro method to observe E-selectin-mediated interactions between prostate
      circulating tumor cells derived from patients and human endothelial cells.
AB  - Metastasis is a process in which tumor cells shed from the primary tumor
      intravasate blood vascular and lymphatic system, thereby, gaining access to
      extravasate and form a secondary niche. The extravasation of tumor cells from the
      blood vascular system can be studied using endothelial cells (ECs) and tumor
      cells obtained from different cell lines. Initial studies were conducted using
      static conditions but it has been well documented that ECs behave differently
      under physiological flow conditions. Therefore, different flow chamber assemblies
      are currently being used to studying cancer cell interactions with ECs. Current
      flow chamber assemblies offer reproducible results using either different cell
      lines or fluid at different shear stress conditions. However, to observe and
      study interactions with rare cells such as circulating tumor cells (CTCs),
      certain changes are required to be made to the conventional flow chamber
      assembly. CTCs are a rare cell population among millions of blood cells.
      Consequently, it is difficult to obtain a pure population of CTCs. Contamination
      of CTCs with different types of cells normally found in the circulation is
      inevitable using present enrichment or depletion techniques. In the present
      report, we describe a unique method to fluorescently label circulating prostate
      cancer cells and study their interactions with ECs in a self-assembled flow
      chamber system. This technique can be further applied to observe interactions
      between prostate CTCs and any protein of interest.

PMID- 24894375
TI  - Esophageal peristaltic defects in adults with functional dysphagia.
AB  - Functional dysphagia (FD) is characterized by the presence of dysphagia without
      evidence of mechanical esophageal obstruction, GERD, and histopathology-based
      esophageal motor disorders. Dysphagia is common in older patients; however, there
      is a paucity of information regarding the type and frequency of peristaltic
      abnormalities compared to younger patients. Based on recently validated criteria
      for classification of weak peristalsis using high-resolution manometry (HRM), we
      hypothesized that older patients with FD would have more peristaltic defects
      detected by HRM compared to younger FD patients. A retrospective review of our
      motility database yielded 65 patients that met inclusion criteria. Patients were
      divided into two groups based on age (younger: <70 years; older: >=70 years).
      Patients were interviewed, completed a quality-of-life questionnaire, and
      underwent solid-state HRM. The two groups differed in age but in no other
      demographic characteristics, severity of dysphagia, or quality of life. Dyspeptic
      symptoms, including nausea (p < 0.001), early satiety (p = 0.01), bloating (p =
      0.02), and belching (p = 0.01), were also more prevalent in younger FD patients.
      Older age was associated with weak peristalsis involving frequent failed
      peristalsis, small proximal peristaltic defects (2-5 cm), and large proximal
      peristaltic defects (>5 cm) (p < 0.001). The mean contraction amplitude was also
      lower in the older group (p < 0.05). These data support the hypothesis that older
      patients with FD have a higher frequency of peristaltic abnormalities on HRM
      compared to younger patients. Older age was associated with increased frequency
      of weak peristalsis with small and large peristaltic defects. 

PMID- 24894376
TI  - Men's attitudes on gender equality and their contraceptive use in Uttar Pradesh
      India.
AB  - BACKGROUND: Men play crucial role in contraceptive decision-making, particularly
      in highly gender-stratified populations. Past research examined men's attitudes
      toward fertility and contraception and the association with actual contraceptive
      practices. More research is needed on whether men's attitudes on gender equality
      are associated with contraceptive behaviors; this is the objective of this study.
      METHODS: This study uses baseline data of the Measurement, Learning, and
      Evaluation (MLE) Project for the Urban Health Initiative in Uttar Pradesh, India.
      Data were collected from a representative sample of 6,431 currently married men
      in four cities of the state. Outcomes are current use of contraception and
      contraceptive method choice. Key independent variables are three gender measures:
      men's attitudes toward gender equality, gender sensitive decision making, and
      restrictions on wife's mobility. Multivariate analyses are used to identify the
      association between the gender measures and contraceptive use. RESULTS: Most men
      have high or moderate levels of gender sensitive decision-making, have low to
      moderate levels of restrictions on wife's mobility, and have moderate to high
      levels of gender equitable attitudes in all four cities. Gender sensitive
      decision making and equitable attitudes show significant positive association and
      restrictions on wife's mobility showed significant negative relationship with
      current contraceptive use. CONCLUSION: The study demonstrates that contraceptive
      programs need to engage men and address gender equitable attitudes; this can be
      done through peer outreach (interpersonal communication) or via mass media.
      Engaging men to be more gender equal may have an influence beyond contraceptive
      use in contexts where men play a crucial role in household decision-making.

PMID- 24894378
TI  - Stimulated recall methodology for assessing work system barriers and facilitators
      in family-centered rounds in a pediatric hospital.
AB  - Human factors and ergonomics methods are needed to redesign healthcare processes
      and support patient-centered care, in particular for vulnerable patients such as
      hospitalized children. We implemented and evaluated a stimulated recall
      methodology for collective confrontation in the context of family-centered
      rounds. Five parents and five healthcare team members reviewed video records of
      their bedside rounds, and were then interviewed using the stimulated recall
      methodology to identify work system barriers and facilitators in family-centered
      rounds. The evaluation of the methodology was based on a survey of the
      participants, and a qualitative analysis of interview data in light of the work
      system model of Smith and Carayon (1989, 2001). Positive survey feedback from the
      participants was received. The stimulated recall methodology identified barriers
      and facilitators in all work system elements. Participatory ergonomics methods
      such as the stimulated recall methodology allow a range of participants,
      including parents and children, to participate in healthcare process improvement.

PMID- 24894380
TI  - Stimulation of erythrocyte cell membrane scrambling by nystatin.
AB  - The antifungal ionophore nystatin dissipates the Na(+) and K(+) gradients across
      the cell membrane, leading to cellular gain of Na(+) and cellular loss of K(+) .
      The increase of cellular Na(+) concentration may result in Ca(2+) accumulation in
      exchange for Na(+) . Increase of cytosolic Ca(2+) activity ([Ca(2+) ]i ) and loss
      of cellular K(+) foster apoptosis-like suicidal erythrocyte death or eryptosis,
      which is characterised by cell shrinkage and cell membrane scrambling leading to
      phosphatidylserine exposure at the erythrocyte surface. The present study
      explored whether nystatin stimulates eryptosis. Cell volume was estimated from
      forward scatter (FSC), phosphatidylserine exposure from annexin V binding and
      [Ca(2+) ]i from Fluo3-fluorescence in flow cytometry. A 48-hr exposure to
      nystatin (15 MUg/ml) was followed by a significant increase of [Ca(2+) ]i , a
      significant increase of annexin V binding and a significant decrease of FSC. The
      annexin V binding after nystatin treatment was significantly blunted in the
      nominal absence of extracellular Ca(2+) . Partial replacement of extracellular
      Na(+) with extracellular K(+) blunted the nystatin-induced erythrocyte shrinkage
      but increased [Ca(2+) ]i and annexin V binding. Nystatin triggers cell membrane
      scrambling, an effect at least partially due to entry of extracellular Ca(2+) . 

PMID- 24894381
TI  - "Is macromolecular crowding overlooked?"--Effects of volume exclusion on DNA
      amino acids complexes and their reconstitutes.
AB  - Biological macromolecules evolve and function within intracellular environments
      that are crowded with other macromolecules. Crowding results in surprisingly
      large quantitative effects on both the rates and the equilibria of interactions
      involving macromolecules, but such interactions are commonly studied outside the
      cell in uncrowded buffers. The addition of high concentrations of natural and
      synthetic macromolecules to such buffers enables crowding to be mimicked in
      vitro, and should be encouraged as a routine variable to study. In this study, we
      propose to understand the changes in DNA character and its modulation in presence
      of macromolecules such as PEG with reference to binding parameters to amino acids
      using fluorescence enhancement. 

PMID- 24894382
TI  - Transcultural and psychometric validation of the Dispositional Resilience Scale
      (DRS-15) in Chinese adult women.
AB  - PURPOSE: The aim of this study was to report translation and transcultural
      adaptation of the 15-item Dispositional Resilience Scale in traditional Chinese
      (C-DRS-15) and evaluate its psychometric properties. METHODS: The DRS is a self
      report instrument that measures psychological hardiness. We followed an
      international standard of cross-cultural translation and validation of patient
      reported outcome measures to create the Chinese version. Then, the translated C
      DRS-15 was validated on 542 Chinese women from a population-based sample in Hong
      Kong. RESULTS: The internal consistency and criterion-related validity were
      investigated. Exploratory and confirmatory factor analysis revealed that the C
      DRS-15 was supported by a modified three-factor structure in our Chinese sample
      (RMSEA = .06, CFI = .94, TLI = .92, and SRMR = .06). The reliability (Cronbach's
      alpha coefficient = .78) and validity were satisfactory. Total resilience score
      was negatively correlated with depression (p < .001), with non-depressed women
      scoring higher on the C-DRS-15. CONCLUSIONS: The C-DRS-15 was demonstrated to be
      a reliable and valid measurement to assess hardiness in Chinese women.

PMID- 24894379
TI  - A framework for application of metabolic modeling in yeast to predict the effects
      of nsSNV in human orthologs.
AB  - BACKGROUND: We have previously suggested a method for proteome wide analysis of
      variation at functional residues wherein we identified the set of all human genes
      with nonsynonymous single nucleotide variation (nsSNV) in the active site residue
      of the corresponding proteins. 34 of these proteins were shown to have a 1:1:1
      enzyme:pathway:reaction relationship, making these proteins ideal candidates for
      laboratory validation through creation and observation of specific yeast active
      site knock-outs and downstream targeted metabolomics experiments. Here we present
      the next step in the workflow toward using yeast metabolic modeling to predict
      human metabolic behavior resulting from nsSNV. RESULTS: For the previously
      identified candidate proteins, we used the reciprocal best BLAST hits method
      followed by manual alignment and pathway comparison to identify 6 human proteins
      with yeast orthologs which were suitable for flux balance analysis (FBA). 5 of
      these proteins are known to be associated with diseases, including ribose 5
      phosphate isomerase deficiency, myopathy with lactic acidosis and sideroblastic
      anaemia, anemia due to disorders of glutathione metabolism, and two porphyrias,
      and we suspect the sixth enzyme to have disease associations which are not yet
      classified or understood based on the work described herein. CONCLUSIONS:
      Preliminary findings using the Yeast 7.0 FBA model show lack of growth for only
      one enzyme, but augmentation of the Yeast 7.0 biomass function to better simulate
      knockout of certain genes suggested physiological relevance of variations in
      three additional proteins. Thus, we suggest the following four proteins for
      laboratory validation: delta-aminolevulinic acid dehydratase, ferrochelatase,
      ribose-5 phosphate isomerase and mitochondrial tyrosyl-tRNA synthetase. This
      study indicates that the predictive ability of this method will improve as more
      advanced, comprehensive models are developed. Moreover, these findings will be
      useful in the development of simple downstream biochemical or mass-spectrometric
      assays to corroborate these predictions and detect presence of certain known
      nsSNVs with deleterious outcomes. Results may also be useful in predicting as yet
      unknown outcomes of active site nsSNVs for enzymes that are not yet well
      classified or annotated.

PMID- 24894383
TI  - Using quantitative methods within the Universalist model framework to explore the
      cross-cultural equivalence of patient-reported outcome instruments.
AB  - PURPOSE: The cross-cultural equivalence of patient-reported outcome (PRO)
      instruments is critical when they are used in international settings. The
      Universalist model of equivalence was proposed as a framework to investigate
      cross-cultural equivalence. The purpose of this paper was to illustrate how
      quantitative methods can be used to investigate cross-cultural equivalence within
      this framework. METHODS: The six types of equivalence of the Universalist model
      were reviewed from a statistical perspective and statistical techniques allowing
      addressing the underlying question were identified. These methods are described
      and examples are provided of how they can be applied. An integrated pragmatic
      approach to the exploration of cross-cultural equivalence was developed based on
      these methods. RESULTS: The statistical techniques identified were factor
      analysis to explore conceptual equivalence, differential item functioning to
      explore semantic and item equivalence, and comparison of measurement properties
      for the measurement equivalence. The statistical techniques addressing
      operational equivalence were found to be diverse and highly specific to the
      operational aspect under investigation. Functional equivalence involves a
      comprehensive appraisal of the potential impact of the results of the other
      equivalences on the conclusions of the research. This structured appraisal of
      functional equivalence offers a framework for a comprehensive, but flexible,
      approach for the efficient application of statistical analyses to explore cross
      cultural equivalence of PRO instruments. CONCLUSION: The different types of
      equivalence of the Universalist model can be investigated using quantitative
      methods. An integrated approach, which could be used in a variety of settings,
      was developed to allow the whole notion of cross-cultural equivalence to be
      comprehensively and efficiently addressed.

PMID- 24894377
TI  - Antiretroviral treatment response of HIV-infected children after prevention of
      mother-to-child transmission in West Africa.
AB  - INTRODUCTION: We assessed the rate of treatment failure of HIV-infected children
      after 12 months on antiretroviral treatment (ART) in the Paediatric IeDEA West
      African Collaboration according to their perinatal exposure to antiretroviral
      drugs for preventing mother-to-child transmission (PMTCT). METHODS: A
      retrospective cohort study in children younger than five years at ART initiation
      between 2004 and 2009 was nested within the pWADA cohort, in Bamako-Mali and
      Abidjan-Cote d'Ivoire. Data on PMTCT exposure were collected through a direct
      review of children's medical records. The 12-month Kaplan-Meier survival without
      treatment failure (clinical or immunological) was estimated and their baseline
      factors studied using a Cox model analysis. Clinical failure was defined as the
      appearance or reappearance of WHO clinical stage 3 or 4 events or any death
      occurring within the first 12 months of ART. Immunological failure was defined
      according to the 2006 World Health Organization age-related immunological
      thresholds for severe immunodeficiency. RESULTS: Among the 1035 eligible
      children, PMTCT exposure was only documented for 353 children (34.1%) and
      remained unknown for 682 (65.9%). Among children with a documented PMTCT
      exposure, 73 (20.7%) were PMTCT exposed, of whom 61.0% were initiated on a
      protease inhibitor-based regimen, and 280 (79.3%) were PMTCT unexposed. At 12
      months on ART, the survival without treatment failure was 40.6% in the PMTCT
      exposed group, 25.2% in the unexposed group and 18.5% in the children with
      unknown exposure status (p=0.002). In univariate analysis, treatment failure was
      significantly higher in children unexposed (HR 1.4; 95% CI: 1.0-1.9) and with
      unknown PMTCT exposure (HR 1.5; 95% CI: 1.2-2.1) rather than children PMTCT
      exposed (p=0.01). In the adjusted analysis, treatment failure was not
      significantly associated with PMTCT exposure (p=0.15) but was associated with
      immunodeficiency (aHR 1.6; 95% CI: 1.4-1.9; p=0.001), AIDS clinical events (aHR
      1.4; 95% CI: 1.0-1.9; p=0.02) at ART initiation and receiving care in Mali
      compared to Cote d'Ivoire (aHR 1.2; 95% CI: 1.0-1.4; p=0.04). CONCLUSIONS:
      Despite a low data quality, PMTCT-exposed West African children did not have a
      poorer 12-month response to ART than others. Immunodeficiency and AIDS events at
      ART initiation remain the main predictors associated with treatment failure in
      this operational context.

PMID- 24894385
TI  - Spinal cord transection in the larval zebrafish.
AB  - Mammals fail in sensory and motor recovery following spinal cord injury due to
      lack of axonal regrowth below the level of injury as well as an inability to
      reinitiate spinal neurogenesis. However, some anamniotes including the zebrafish
      Danio rerio exhibit both sensory and functional recovery even after complete
      transection of the spinal cord. The adult zebrafish is an established model
      organism for studying regeneration following spinal cord injury, with sensory and
      motor recovery by 6 weeks post-injury. To take advantage of in vivo analysis of
      the regenerative process available in the transparent larval zebrafish as well as
      genetic tools not accessible in the adult, we use the larval zebrafish to study
      regeneration after spinal cord transection. Here we demonstrate a method for
      reproducibly and verifiably transecting the larval spinal cord. After
      transection, our data shows sensory recovery beginning at 2 days post-injury
      (dpi), with the C-bend movement detectable by 3 dpi and resumption of free
      swimming by 5 dpi. Thus we propose the larval zebrafish as a companion tool to
      the adult zebrafish for the study of recovery after spinal cord injury.

PMID- 24894384
TI  - New-onset diabetes after kidney transplant in children.
AB  - The development of new-onset diabetes after kidney transplantation (NODAT) is
      associated with reduced graft function, increased cardiovascular morbidity and
      lower patient survival among adult recipients. In the pediatric population,
      however, the few studies examining NODAT have yielded inconsistent results.
      Therefore, the true incidence of NODAT in the pediatric population has been
      difficult to establish. The identification of children and adolescents at risk
      for NODAT requires appropriate screening questions and tests pre- and post-kidney
      transplant. Several risk factors have been implicated in the pathogenesis of
      NODAT and post-transplant glucose intolerance, including African American race,
      obesity, family history of diabetes and the type of immunosuppressant regimen.
      Moreover, uremia per se results in a state of insulin resistance that increases
      the risk of developing diabetes post-transplant. When an individual becomes
      glucose intolerant, early lifestyle modification and antihyperglycemic measures
      with tailoring of the immunosuppressant regimen should be implemented to prevent
      the development of NODAT. For the child or adolescent with NODAT,
      antihyperglycemic therapy should be prescribed in order to achieve optimal
      glycemic control, ultimately reducing complications and improving overall
      allograft and patient survival. In this article, we review the risk factors,
      screening methods, diagnosis, management and outcome of children and adolescents
      with NODAT and post-kidney transplant glucose intolerance. 

PMID- 24894387
TI  - Charting cognitive and volumetric trajectories after stroke: protocol for the
      Cognition And Neocortical Volume After Stroke (CANVAS) study.
AB  - RATIONALE: Globally, stroke and dementia are leading causes of disability and
      mortality. More than one third of stroke patients will develop dementia, but
      mechanisms are unclear. AIMS: The study aims to establish whether brain volume
      change is associated with poststroke dementia, and to elucidate potential causal
      mechanisms, including genetic markers, amyloid deposition and vascular risk
      factors. An understanding of whether - and in whom - stroke is neurodegenerative
      is critical for the strategic use of potential disease-modifying therapies.
      HYPOTHESES: That stroke patients will exhibit greater brain volume loss than
      comparable cohorts of stroke-free controls; and that those who develop dementia
      will exhibit greater brain volume loss than those who do not. DESIGN: Advanced
      brain imaging techniques are used to longitudinally measure brain volume and
      cortical thickness in 135 stroke patients. Concurrent neuropsychological testing
      will correlate clinical profile with these measures. PRIMARY OUTCOMES: Primary
      imaging end-point is brain volume change between three-months and three-years
      poststroke; primary clinical outcome is the presence of dementia at three-years.
      SECONDARY OUTCOMES: We will examine the correlations with the following
      variables: dementia subtype; physical activity levels; behavioral dysfunction as
      measured by patient and caregiver-reported scales; structural and functional
      brain connectivity disruption; apolipoprotein E; and specific neuropsychological
      test scores. DISCUSSION: Magnetic resonance imaging markers of structural brain
      aging and performance on neuropsychological tests are powerful predictors of
      dementia. We need to understand the trajectory of regional brain volume change
      and cognitive decline in patients after stroke. This will allow future risk
      stratification for prognostic counseling, service planning, and early therapeutic
      intervention.

PMID- 24894386
TI  - An efficacy and mechanism evaluation study of Levosimendan for the Prevention of
      Acute oRgan Dysfunction in Sepsis (LeoPARDS): protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Organ dysfunction consequent to infection ('severe sepsis') is the
      leading cause of admission to an intensive care unit (ICU). In both animal models
      and early clinical studies the calcium channel sensitizer levosimendan has been
      demonstrated to have potentially beneficial effects on organ function. The aims
      of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis
      (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will
      improve organ dysfunction in adults who have septic shock and to establish the
      safety profile of levosimendan in this group of patients. METHODS/DESIGN: This is
      a multicenter, randomized, double-blind, parallel group, placebo-controlled
      trial. Adults fulfilling the criteria for systemic inflammatory response syndrome
      due to infection, and requiring vasopressor therapy, will be eligible for
      inclusion in the trial. Within 24 hours of meeting these inclusion criteria,
      patients will be randomized in a 1:1 ratio stratified by the ICU to receive
      either levosimendan (0.05 to 0.2 MUg.kg-1.min-1 or placebo for 24 hours in
      addition to standard care. The primary outcome measure is the mean Sequential
      Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes
      include: central venous oxygen saturations and cardiac output; incidence and
      severity of renal failure using the Acute Kidney Injury Network criteria;
      duration of renal replacement therapy; serum bilirubin; time to liberation from
      mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and
      hospital length-of-stay; and days free from catecholamine therapy. Blood and
      urine samples will be collected on the day of inclusion, at 24 hours, and on days
      4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan
      might improve organ function. Eighty patients will have additional blood samples
      taken to measure levels of levosimendan and its active metabolites OR-1896 and OR
      1855. A total of 516 patients will be recruited from approximately 25 ICUs in the
      United Kingdom. DISCUSSION: This trial will test the efficacy of levosimendan to
      reduce acute organ dysfunction in adult patients who have septic shock and
      evaluate its biological mechanisms of action. TRIAL REGISTRATION: Current
      controlled trials ISRCTN12776039 (19 September 2013).

PMID- 24894388
TI  - Mixed Nipple Infections Caused by Variant of BPV3 and a Putative New Subtype of
      BPV in Cattle.
AB  - Bovine papilloma is a chronic and proliferative skin and mucosal wart caused by
      Bovine papillomavirus (BPV). In June, 2013, a leaf-and flat-shaped wart disease
      was observed on the nipple skins in a cattle farm in Xinjiang. To diagnose the
      disease, we collected the diseased skins for pathological biopsy and DNA analysis
      by PCR amplification using a pair of degenerate primers FAP59 and FAP64.
      Sequencing and phylogenetic analysis showed that the infection was caused by a
      variant of BPV3 and putatively a new subtype of BPV (BPV/CHI-SW1, belonging to
      the Xi papillomavirus genus). This is the first report of mixed infection caused
      by variant of BPV3 and BPV (putatively new subtype) in China, and would be of
      importance for the molecular epidemiological study of the disease. 

PMID- 24894391
TI  - 18F-fluorodopa positron-emission tomography: an emerging imaging modality for
      patients with brain metastases.
AB  - MRI is the preferred method for the diagnosis and monitoring of brain metastases.
      However, MRI does not provide enough information in some important instances. We
      explore the potential applications of (18)F-fluorodopa ((18)F-FDOPA) PET for
      patients with brain metastases. Accurate differentiation between tumor recurrence
      and radiation injury might be possible with the use of (18)F-FDOPA PET. Semi
      quantitative and qualitative parameters achieved similar results. Kinetic
      analysis and time-activity curve patterns could further improve accuracy. (18)F
      FDOPA PET also had prognostic value in this setting. Combining the high
      resolution of MRI with the metabolic information provided by (18)F-FDOPA PET
      could improve recurrent tumor contouring precision for biopsy, resection or
      radiation. The promising applications of (18)F-FDOPA PET imaging in the treatment
      monitoring and planning of brain metastatic tumors require further corroboration
      but could soon become important instruments to improve diagnostic accuracy,
      prognosis prediction and treatment planning of the growing population of patients
      with brain metastatic disease. 

PMID- 24894389
TI  - Metabolic and transcriptional regulatory mechanisms underlying the anoxic
      adaptation of rice coleoptile.
AB  - The ability of rice to germinate under anoxia by extending the coleoptile is a
      highly unusual characteristic and a key feature underpinning the ability of rice
      seeds to establish in such a stressful environment. The process has been a focal
      point for research for many years. However, the molecular mechanisms underlying
      the anoxic growth of the coleoptile still remain largely unknown. To unravel the
      key regulatory mechanisms of rice germination under anoxic stress, we combined in
      silico modelling with gene expression data analysis. Our initial modelling
      analysis via random flux sampling revealed numerous changes in rice primary
      metabolism in the absence of oxygen. In particular, several reactions associated
      with sucrose metabolism and fermentation showed a significant increase in flux
      levels, whereas reaction fluxes across oxidative phosphorylation, the
      tricarboxylic acid cycle and the pentose phosphate pathway were down-regulated.
      The subsequent comparative analysis of the differences in calculated fluxes with
      previously published gene expression data under air and anoxia identified at
      least 37 reactions from rice central metabolism that are transcriptionally
      regulated. Additionally, cis-regulatory content analyses of these
      transcriptionally controlled enzymes indicate a regulatory role for transcription
      factors such as MYB, bZIP, ERF and ZnF in transcriptional control of genes that
      are up-regulated during rice germination and coleoptile elongation under anoxia. 

PMID- 24894390
TI  - Mechanical vulnerability explains size-dependent mortality of reef corals.
AB  - Understanding life history and demographic variation among species within
      communities is a central ecological goal. Mortality schedules are especially
      important in ecosystems where disturbance plays a major role in structuring
      communities, such as coral reefs. Here, we test whether a trait-based,
      mechanistic model of mechanical vulnerability in corals can explain mortality
      schedules. Specifically, we ask whether species that become increasingly
      vulnerable to hydrodynamic dislodgment as they grow have bathtub-shaped mortality
      curves, whereas species that remain mechanically stable have decreasing mortality
      rates with size, as predicted by classical life history theory for reef corals.
      We find that size-dependent mortality is highly consistent between species with
      the same growth form and that the shape of size-dependent mortality for each
      growth form can be explained by mechanical vulnerability. Our findings highlight
      the feasibility of predicting assemblage-scale mortality patterns on coral reefs
      with trait-based approaches. 

PMID- 24894392
TI  - Superimposed electrical stimulation improves mobility of pre-stiff thumbs after
      ulnar collateral ligament injury of the metacarpophalangeal joint: a randomized
      study.
AB  - OBJECTIVE: This study aimed at testing the ability of the superimposed electrical
      stimulation technique to restore the mobility of pre-stiff thumbs after operative
      repair for rupture of the ulnar collateral ligament. MATERIAL AND METHODS: Eight
      patients demonstrating a pre-stiff metacarpophalangeal joint were involved in two
      rehabilitation sessions of a counterbalanced design. In the voluntary contraction
      session, they performed 20min of repeated active flexions of the impaired
      metacarpophalangeal joint. In the superimposed electrical stimulation session,
      they performed 20min of percutaneous neuromuscular electrical stimulations which
      were superimposed to voluntary flexion. RESULTS: Mean active range of motion
      improvement from pre- to post-session was significantly greater in the
      superimposed electrical stimulation condition compared to the voluntary
      contraction condition (11+/-5 deg versus 3+/-4 deg; P<0.01). CONCLUSION:
      Superimposing electrical stimulation to voluntary contractions is an efficient
      technique to improve active range of motion of the pre-stiff metacarpophalangeal
      joint of the thumb.

PMID- 24894393
TI  - Oesophageal varices, schistosomiasis, and mortality among patients admitted with
      haematemesis in Mwanza, Tanzania: a prospective cohort study.
AB  - BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common cause of hospital
      admissions worldwide. Aetiologies vary by sociodemographics and geography.
      Retrospective studies of endoscopies in much of Africa have documented
      oesophageal varices as a leading cause of UGIB. Prospective studies describing
      outcomes and associations with clinical factors are lacking. METHODS: We
      conducted a prospective cohort study at a referral hospital in Mwanza, Tanzania
      where schistosomiasis is endemic. Adults admitted with haematemesis underwent
      laboratory workup, schistosomiasis antigen testing and elective endoscopy, and
      were followed for two months for death or re-bleeding. We assessed predictors of
      endoscopic findings using logistic regression models, and determined prediction
      rules that maximised sensitivity and positive predictive value (PPV). RESULTS: Of
      124 enrolled patients, 13 died within two months (10%); active schistosomiasis
      prevalence was 48%. 64/91(70%) patients had oesophageal varices. We found strong
      associations between varices and numerous demographic or clinical findings,
      permitting construction of simple, high-fidelity prediction rules for oesophageal
      varices applicable even in rural settings. Portal vein diameter >= 13 mm or water
      sourced from the lake yielded sensitivity, specificity, PPV and NPV >90% for
      oesophageal varices; presence of splenomegaly or water sourced from the lake
      maintained sensitivity and PPV >90%. CONCLUSIONS: Our results guide
      identification of patients, via ultrasound and clinical examination, likely to
      have varices for whom referral for endoscopy may be life-saving. Furthermore,
      they support empiric anti-schistosome treatment for patients with UGIB in
      schistosome-endemic regions. These interventions have potential to reduce UGIB
      related morbidity and mortality in Africa.

PMID- 24894395
TI  - Choroidal structure in normal eyes and after photodynamic therapy determined by
      binarization of optical coherence tomographic images.
AB  - PURPOSE: To determine changes in choroidal structure by binarization of optical
      coherence tomographic (OCT) images. METHODS: Choroidal images were recorded by
      enhanced depth imaging OCT. The subfoveal choroidal images were analyzed, and the
      luminal and interstitial areas were converted to binary images by the Niblack
      method. The interrater, intrarater, and intersession agreements of the binary
      images were determined for healthy eyes. In eyes with age-related macular
      degeneration (AMD), the binary images of the choroid before photodynamic therapy
      (PDT) were compared to those after PDT. The untreated fellow eyes were studied as
      controls. RESULTS: In healthy eyes, the average ratio of the luminal to choroidal
      area was 65.4%. The interrater agreement rate was high, with intraclass
      correlation coefficient (ICC) 0.985 and 0.988 for the choroid and luminal areas,
      respectively. The intrarater ICC was 0.996 for the choroid and 0.997 for the
      luminal areas. The intersession ICC was 0.993 for the choroid and 0.984 for the
      luminal areas. In eyes with AMD, the subfoveal choroidal area, the luminal area,
      and the interstitial areas were thinner 6 months after PDT (all P < 0.01,
      Wilcoxon signed-rank sum test). The ratio of the luminal to choroidal area was
      significantly decreased to 62.8% (P < 0.01, Wilcoxon signed-rank sum test). The
      ratio for the fellow eyes was not significantly changed. CONCLUSIONS: The Niblack
      binarization method can be used to analyze the luminal area of choroid in an OCT
      image with good repeatability and reproducibility. The change in the subfoveal
      choroidal area after PDT is due mainly to a decrease in the luminal areas.

PMID- 24894397
TI  - Role of soluble vascular endothelial growth factor receptors-1 and -2, their
      ligands, and other factors in branch retinal vein occlusion with macular edema.
AB  - PURPOSE: To evaluate the association between multiple factors in aqueous humor
      and the severity of macular edema in patients with branch retinal vein occlusion
      (BRVO). METHODS: We measured the aqueous humor levels of 11 factors (including
      vascular endothelial growth factor receptors, growth factors, and inflammatory
      factors) in BRVO patients with macular edema and in cataract patients as
      controls. Aqueous humor samples were obtained from 40 patients (31 patients with
      BRVO and 9 with cataract). Then the levels of vascular endothelial growth factor
      (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor
      (PlGF), soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic
      protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL
      8, IL-12(p70), and IL-13 were measured by the suspension array method. Macular
      edema was examined by optical coherence tomography, and its severity was
      determined from the central macular thickness (CMT), neurosensory retinal
      thickness (TNeuro), and subfoveal serous retinal thickness (SRT). RESULTS:
      Aqueous humor levels of growth factors, sVEGFR-1, sVEGFR-2, and inflammatory
      factors were significantly higher in eyes with BRVO than in control eyes. Aqueous
      levels of sVEGFR-1 and -2 were significantly correlated with the SRT, as well as
      with the levels of growth factors (PIGF and PDGF-AA) and various inflammatory
      factors (sICAM-1, MCP-1, IL-6, and IL-8). Levels of the growth factors (VEGF,
      PlGF, and PDGF-AA) were also significantly correlated with each other.
      CONCLUSIONS: These findings suggest the importance of the cytokine network in
      BRVO patients, and may contribute to understanding the mechanism of macular edema
      associated with BRVO and to development of new treatments.

PMID- 24894394
TI  - Microscopic inner retinal hyper-reflective phenotypes in retinal and neurologic
      disease.
AB  - PURPOSE: We surveyed inner retinal microscopic features in retinal and neurologic
      disease using a reflectance confocal adaptive optics scanning light
      ophthalmoscope (AOSLO). METHODS: Inner retinal images from 101 subjects affected
      by one of 38 retinal or neurologic conditions and 11 subjects with no known eye
      disease were examined for the presence of hyper-reflective features other than
      vasculature, retinal nerve fiber layer, and foveal pit reflex. The hyper
      reflective features in the AOSLO images were grouped based on size, location, and
      subjective texture. Clinical imaging, including optical coherence tomography
      (OCT), scanning laser ophthalmoscopy, and fundus photography was analyzed for
      comparison. RESULTS: Seven categories of hyper-reflective inner retinal
      structures were identified, namely punctate reflectivity, nummular (disc-shaped)
      reflectivity, granular membrane, waxy membrane, vessel-associated membrane,
      microcysts, and striate reflectivity. Punctate and nummular reflectivity also was
      found commonly in normal volunteers, but the features in the remaining five
      categories were found only in subjects with retinal or neurologic disease. Some
      of the features were found to change substantially between follow up imaging
      months apart. CONCLUSIONS: Confocal reflectance AOSLO imaging revealed a diverse
      spectrum of normal and pathologic hyper-reflective inner and epiretinal features,
      some of which were previously unreported. Notably, these features were not
      disease-specific, suggesting that they might correspond to common mechanisms of
      degeneration or repair in pathologic states. Although prospective studies with
      larger and better characterized populations, along with imaging of more extensive
      retinal areas are needed, the hyper-reflective structures reported here could be
      used as disease biomarkers, provided their specificity is studied further.

PMID- 24894398
TI  - Inhibition by all-trans-retinoic acid of transforming growth factor-beta-induced
      collagen gel contraction mediated by human tenon fibroblasts.
AB  - PURPOSE: Excessive wound contraction can lead to scar formation in the
      conjunctiva. The effects of all-trans-retinoic acid (ATRA) on the contractility
      of human Tenon fibroblasts (HTFs) cultured in three-dimensional (3D) collagen
      gels were investigated. METHODS: Human Tenon fibroblasts were cultured in 3D gels
      of type I collagen and in the absence or presence of TGF-beta, ATRA, or various
      inhibitors. Collagen gel contraction was evaluated by measurement of gel
      diameter. Phosphorylation of various signaling molecules was examined by
      immunoblot analysis. The formation of actin stress fibers and focal adhesions was
      detected by laser confocal microscopy. RESULTS: All-trans-retinoic acid inhibited
      TGF-beta-induced collagen gel contraction mediated by HTFs in a concentration-
      and time-dependent manner. The TGF-beta-induced phosphorylation of focal adhesion
      kinase (FAK) and formation of stress fibers and focal adhesions in HTFs were
      attenuated by ATRA. All-trans-retinoic acid also inhibited the TGF-beta-induced
      phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular
      signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK) as well
      as that of c-Jun and Smad2/3. Furthermore, TGF-beta-induced collagen gel
      contraction was blocked by inhibitors of ERK, p38, or JNK signaling. CONCLUSIONS:
      All-trans-retinoic acid inhibited TGF-beta-induced collagen gel contraction
      mediated by HTFs, most likely by attenuating the formation of actin stress fibers
      and focal adhesions as well as signaling by MAPKs, c-Jun, and Smads. All-trans
      retinoic acid may therefore prove effective for inhibition of conjunctival
      scarring through attenuation of the contractility of Tenon fibroblasts.

PMID- 24894399
TI  - The vasoneuronal effects of AT1 receptor blockade in a rat model of retinopathy
      of prematurity.
AB  - PURPOSE: Retinal angiogenesis, neural dysfunction, and microglial activation
      occur in both humans with retinopathy of prematurity and in animal models of the
      disease. The aim of this study was to assess whether blockade of the renin
      angiotensin system ameliorated these effects in rats with oxygen induced
      retinopathy (OIR). METHODS: Sprague-Dawley rats were treated with 80% oxygen from
      birth to postnatal day (P)11 and were then placed in normal air until
      experimentation at P18, while control animals remained in normal air. Control and
      OIR rats were treated with the angiotensin II type 1 receptor (AT1 receptor)
      antagonist, valsartan (4, 10, or 40 mg/kg daily, intraperitoneally). Retinal
      function was assessed using the twin-flash electroretinogram and
      immunocytochemistry was used to evaluate vascular change and microglial
      activation. RESULTS: Oxygen-induced retinopathy was associated with growth of
      blood vessels into the vitreous in the peripheral retina, increased microglial
      number, and activation and a reduction in both rod and cone pathway function.
      Although treatment with valsartan reduced growth of vessels into the vitreous, it
      also reduced the formation of the deep vascular plexus. Valsartan treatment
      reduced microglial number and activation; however, it did not ameliorate neural
      dysfunction. At the highest dose examined, valsartan treatment reduced
      photoreceptor and inner retinal function in both the control and OIR animals.
      CONCLUSIONS: Valsartan was effective in reducing physiological and pathological
      angiogenesis and the microglial inflammatory response, indicating a role for the
      AT1 receptor in these processes, but it did not prevent retinal dysfunction. More
      work is needed to better understand the mechanisms underlying neuronal
      dysfunction in oxygen-induced retinopathy.

PMID- 24894400
TI  - Optic nerve head and peripapillary morphometrics in myopic glaucoma.
AB  - PURPOSE: To investigate morphological characteristics of optic nerve head and
      peripapillary region with myopia and glaucoma. METHODS: Ten normal and 17
      glaucomatous myopic participants were imaged with a custom 1060-nm swept-source
      optical coherence tomography system. The three-dimensional images were processed
      and segmented for inner limiting membrane (ILM), posterior border of retinal
      nerve fiber layer (RNFL), Bruch's membrane (BM), and posterior border of choroid.
      Seven shape parameters were measured: nerve fiber layer (NFL) thickness; Bruch's
      membrane opening (BMO) area, eccentricity, and planarity; BMO and BM depths; and
      choroidal thickness. The results were analyzed by group and regional sector, and
      multiple regression was performed on each shape parameter with age, axial length,
      and glaucoma severity, measured by mean deviation (MD). RESULTS: Bruch's membrane
      opening area (P < 0.001), eccentricity (P = 0.025), and planarity (P = 0.019)
      were correlated with axial length but not with MD, such that larger, more
      elliptical, and less planar BMO was associated with longer axial length. Several
      BMOs displayed a saddle-like shape configuration whose orientation appeared to be
      aligned with that of the BMO ellipse. All BM showed posterior deformation toward
      BMO such that BM closer to BMO was more posterior than that farther from BMO.
      Bruch's membrane depth was correlated with axial length (P = 0.014) and MD (P =
      0.040) in intersubject regression, and BMO depth (P = 0.003) and BM depth (P =
      0.006) were correlated with MD in intereye regression. Bruch's membrane depth was
      also associated with age. Choroidal thickness was negatively correlated with age
      (P = 0.001) and with axial length to a smaller degree (P = 0.034), but not with
      glaucoma severity. CONCLUSIONS: Axial length was a significant factor in BMO and
      BM shape in normal and glaucomatous myopic subjects. Posterior deformation of BM
      was observed in all eyes and significantly associated with functional
      glaucomatous damage and age.

PMID- 24894402
TI  - Classic citations in erectile dysfunction.

PMID- 24894401
TI  - Sirt1, a negative regulator of matrix metalloproteinase-9 in diabetic
      retinopathy.
AB  - PURPOSE: In the pathogenesis of diabetic retinopathy, matrix metalloproteinase
      (MMP)-9 damages retinal mitochondria, activating the apoptotic machinery.
      Transcription of MMP-9 is regulated by nuclear factor kappa B (NF-kappaB), and
      the activation of NF-kappaB is modulated by the acetylation of its p65 subunit.
      Sirtuin 1 (Sirt1), a deacetylase, plays an important role in the acetylation
      deacetylation of p65. The goal of this study is to investigate the role of Sirt1
      in the activation of MMP-9 in diabetic retinopathy. METHODS: The effect of
      hyperglycemia and Sirt1 activator, resveratrol, on acetylation of p65 and its
      binding at MMP-9 promoter-and mitochondrial damage and apoptosis-was assessed in
      the retinal endothelial cells. Role of oxidative stress in the regulation of
      Sirt1 was evaluated in the cells incubated in H2O2. The results were confirmed in
      the retina from diabetic mice with Sod2 or MMP-9 gene manipulated. RESULTS: High
      glucose decreased Sirt1 activity and increased p65 acetylation, and resveratrol
      prevented increase in p65 acetylation, binding of p65 at MMP-9 promoter and MMP-9
      activation, mitochondria damage, and cell apoptosis. While Sirt1 was decreased by
      H2O2, MMP-9 was significantly increased. Retina from wild-type diabetic mice
      presented similar decrease in Sirt1, and diabetic mice with Sod2 overexpression
      or MMP-9 deletion had normal retinal Sirt1. Retinal microvasculature from human
      donors with established diabetic retinopathy also had decreased Sirt1.
      CONCLUSIONS: Thus, in diabetes, increase in oxidative stress inhibits Sirt1 and
      p65 is hyperacetylated, increasing the binding of p65 at MMP-9 promoter.
      Prevention of Sirt1 inhibition, via modulating acetylation of p65, should protect
      activation of MMP-9 and inhibit the development of diabetic retinopathy.

PMID- 24894403
TI  - Motorcycle crashes: attitudes of the motorcyclists regarding riders' experience
      and safety measures.
AB  - Motorcycle injuries constitute a major but neglected emerging public health
      problem in developing countries and contribute significantly to the overall road
      traffic injuries. The aims of this work were to study the attitudes and practices
      of the motorcyclists regarding training and safety measures, and to determine
      some underlying factors of motorcycle crashes. This cross sectional hospital
      based study was conducted on all injured conscious motorcyclists who were
      admitted to the emergency department at Benha University Hospital, Benha City,
      Qalubia governorate, Egypt from December 2012 up to December 2013. The data were
      collected using a standard interview questionnaire which included four main
      sections; personal data, data about the rider's experience and training, safety
      issues and data about the crash the motorcyclist involved in. The questionnaire
      was completed by 246 motorcyclists. Of these, 67.5% did not have a motor cycle
      license and friends/family were the source of training for 56.9% of them. There
      were highly significant associations between the source of training and age,
      education, occupation and marital status (P < 0.001 for all). Correctly
      positioning the motorcycle according to road conditions, making one visible to
      other road users and the proper maintenance of the motorcycle were the most
      commonly reported safety measures. Inattentive mode, suffering stress on the day
      of the accident, not paying attention to distances or to the regulations, not
      being familiar with the road of the accident and not using the protection system
      were some of the underlying factors of motorcycle accidents.

PMID- 24894404
TI  - An inexpensive, interdisciplinary, methodology to conduct an impact study of
      homeless persons on hospital based services.
AB  - Homelessness is a primary concern for community health. Scientific literature on
      homelessness is wide ranging and diverse. One opportunity to add to existing
      literature is the development and testing of affordable, easily implemented
      methods for measuring the impact of homeless on the healthcare system. Such
      methodological approaches rely on the strengths in a multidisciplinary approach,
      including providers, both healthcare and homeless services and applied clinical
      researchers. This paper is a proof of concept for a methodology which is easily
      adaptable nationwide, given the mandated implementation of homeless management
      information systems in the United States and other countries; medical billing
      systems by hospitals; and research methods of researchers. Adaptation is
      independent of geographic region, budget restraints, specific agency skill sets,
      and many other factors that impact the application of a consistent methodological
      science based approach to assess and address homelessness. We conducted a
      secondary data analysis merging data from homeless utilization and hospital case
      based data. These data detailed care utilization among homeless persons in a
      small, Appalachian city in the United States. In our sample of 269 persons who
      received at least one hospital based service and one homeless service between
      July 1, 2012 and June 30, 2013, the total billed costs were $5,979,463 with 10
      people costing more than one-third ($1,957,469) of the total. Those persons were
      primarily men, living in an emergency shelter, with pre-existing disabling
      conditions. We theorize that targeted services, including Housing First, would be
      an effective intervention. This is proposed in a future study. 

PMID- 24894405
TI  - Acute imaging does not improve ASTRAL score's accuracy despite having a
      prognostic value.
AB  - BACKGROUND: The ASTRAL score was recently shown to reliably predict three-month
      functional outcome in patients with acute ischemic stroke. AIM: The study aims to
      investigate whether information from multimodal imaging increases ASTRAL score's
      accuracy. METHODS: All patients registered in the ASTRAL registry until March
      2011 were included. In multivariate logistic-regression analyses, we added
      covariates derived from parenchymal, vascular, and perfusion imaging to the 6
      parameter model of the ASTRAL score. If a specific imaging covariate remained an
      independent predictor of three-month modified Rankin score>2, the area-under-the
      curve (AUC) of this new model was calculated and compared with ASTRAL score's
      AUC. We also performed similar logistic regression analyses in arbitrarily chosen
      patient subgroups. RESULTS: When added to the ASTRAL score, the following
      covariates on admission computed tomography/magnetic resonance imaging-based
      multimodal imaging were not significant predictors of outcome: any stroke-related
      acute lesion, any nonstroke-related lesions, chronic/subacute stroke,
      leukoaraiosis, significant arterial pathology in ischemic territory on computed
      tomography angiography/magnetic resonance angiography/Doppler, significant
      intracranial arterial pathology in ischemic territory, and focal hypoperfusion on
      perfusion-computed tomography. The Alberta Stroke Program Early CT score on plain
      imaging and any significant extracranial arterial pathology on computed
      tomography angiography/magnetic resonance angiography/Doppler were independent
      predictors of outcome (odds ratio: 0.93, 95% CI: 0.87-0.99 and odds ratio: 1.49,
      95% CI: 1.08-2.05, respectively) but did not increase ASTRAL score's AUC (0.849
      vs. 0.850, and 0.8563 vs. 0.8564, respectively). In exploratory analyses in
      subgroups of different prognosis, age or stroke severity, no covariate was found
      to increase ASTRAL score's AUC, either. CONCLUSIONS: The addition of information
      derived from multimodal imaging does not increase ASTRAL score's accuracy to
      predict functional outcome despite having an independent prognostic value. More
      selected radiological parameters applied in specific subgroups of stroke patients
      may add prognostic value of multimodal imaging.

PMID- 24894406
TI  - Catastrophic antiphospholipid syndrome presenting with pulmonary hemorrhage: case
      report.
AB  - This is a case report of catastrophic antiphospholipid syndrome (APLS) involving
      the rare manifestation of pulmonary hemorrhage. This rare variant of APLS is
      frequently life threatening despite medical therapy. The pathogenesis of
      pulmonary hemorrhage in catastrophic APLS remains incompletely understood. The
      optimal approach to managing pulmonary hemorrhage in the setting of catastrophic
      APLS is still unclear, however this case report demonstrates the success of
      combination therapy with anticoagulation, corticosteroids and plasma exchange. 

PMID- 24894407
TI  - Estimating Resource Requirements to Staff a Response to a Medium to Large
      Outbreak of Foot and Mouth Disease in Australia.
AB  - A recent report to the Australian Government identified concerns relating to
      Australia's capacity to respond to a medium to large outbreak of FMD. To assess
      the resources required, the AusSpread disease simulation model was used to
      develop a plausible outbreak scenario that included 62 infected premises in five
      different states at the time of detection, 28 days after the disease entered the
      first property in Victoria. Movements of infected animals and/or contaminated
      product/equipment led to smaller outbreaks in NSW, Queensland, South Australia
      and Tasmania. With unlimited staff resources, the outbreak was eradicated in 63
      days with 54 infected premises and a 98% chance of eradication within 3 months.
      This unconstrained response was estimated to involve 2724 personnel. Unlimited
      personnel was considered unrealistic, and therefore, the course of the outbreak
      was modelled using three levels of staffing and the probability of achieving
      eradication within 3 or 6 months of introduction determined. Under the baseline
      staffing level, there was only a 16% probability that the outbreak would be
      eradicated within 3 months, and a 60% probability of eradication in 6 months.
      Deployment of an additional 60 personnel in the first 3 weeks of the response
      increased the likelihood of eradication in 3 months to 68%, and 100% in 6 months.
      Deployment of further personnel incrementally increased the likelihood of timely
      eradication and decreased the duration and size of the outbreak. Targeted use of
      vaccination in high-risk areas coupled with the baseline personnel resources
      increased the probability of eradication in 3 months to 74% and to 100% in 6
      months. This required 25 vaccination teams commencing 12 days into the control
      program increasing to 50 vaccination teams 3 weeks later. Deploying an equal
      number of additional personnel to surveillance and infected premises operations
      was equally effective in reducing the outbreak size and duration.

PMID- 24894408
TI  - The unmet needs of all adults with ADHD are not the same: a focus on Europe.
AB  - This review discusses the unmet needs in adult ADHD subgroups in Europe:
      adolescents in transition, adult patients, employees, older adults, and those in
      the criminal justice system. Analysis of the literature and an ADHD web forum was
      conducted. The visibility of adult ADHD remains low, and finding professionals
      able to diagnose is difficult for both adolescents as well as adults. Many ADHD
      cases go undiagnosed and untreated; ADHD may be mistaken for other common mental
      health conditions or missed in the presence of comorbidities. Pharmacological and
      psychosocial treatment services are very limited. Most employers do not
      understand how to address ADHD, and employees fear stigmatization. Older age
      individuals (>60 years) may feel worse with unrecognized ADHD, and those
      incarcerated with ADHD are likely to cost disproportionately more than their
      peers, with high recidivism rates. Strategies to address unmet needs and
      accommodate ADHD adults need not be expensive or time consuming to implement. 

PMID- 24894409
TI  - A bioenergetic framework for the temperature dependence of trophic interactions.
AB  - Changing temperature can substantially shift ecological communities by altering
      the strength and stability of trophic interactions. Because many ecological rates
      are constrained by temperature, new approaches are required to understand how
      simultaneous changes in multiple rates alter the relative performance of species
      and their trophic interactions. We develop an energetic approach to identify the
      relationship between biomass fluxes and standing biomass across trophic levels.
      Our approach links ecological rates and trophic dynamics to measure temperature
      dependent changes to the strength of trophic interactions and determine how these
      changes alter food web stability. It accomplishes this by using biomass as a
      common energetic currency and isolating three temperature-dependent processes
      that are common to all consumer-resource interactions: biomass accumulation of
      the resource, resource consumption and consumer mortality. Using this framework,
      we clarify when and how temperature alters consumer to resource biomass ratios,
      equilibrium resilience, consumer variability, extinction risk and transient vs.
      equilibrium dynamics. Finally, we characterise key asymmetries in species
      responses to temperature that produce these distinct dynamic behaviours and
      identify when they are likely to emerge. Overall, our framework provides a
      mechanistic and more unified understanding of the temperature dependence of
      trophic dynamics in terms of ecological rates, biomass ratios and stability. 

PMID- 24894411
TI  - Morphological and clinical feasibility of C3 pedicle screw instrumentation in
      patients with congenital C2-3 fusion.
AB  - PURPOSE: Congenital C2-3 fusion (C2-3CF) is often involved in patients with
      atlantoaxial dislocation, and posterior occipitocervical fixation surgery is
      usually required. Hypoplasia of C2 pedicle is common in such patients, making C2
      pedicle screws (PS) instrumentation inapplicable. Because of congenital fusion,
      C3PS instrumentation would be an ideal alternative for it will not sacrifice an
      additional motion segment; however, the morphological and clinical feasibility
      has not been previously reported. METHODS: We included 42 C2-3CF patients to this
      study and evaluated pedicle trajectories of C2 and C3 using a three-dimensional
      CT. Clinical applications of C3PS instrumentation were evaluated and followed.
      RESULTS: Among the 42 patients, 23 (54.8%) and 8 (19.0%) had C2 and C3 pedicle
      trajectory diameters <4.0 mm, respectively. The bisection line of the fused C2-3
      lamina was used to represent the superior border of C3 articular mass; the entry
      point of C3 pedicle was located at 3 mm inferior to the assumed superior border
      and 3.2 mm medial to the lateral border. Bilateral C3PS instrumentations were
      successfully adopted in 22 patients. No spinal cord or vertebral artery injury
      occurred; postoperative CT showed a trajectory breach rate of 17.4% for C3PS.
      After mean of 3.6-year follow-up, no implant failure was documented. CONCLUSIONS:
      C3PS instrumentation is morphologically and clinically feasible for a large
      proportion of patients with C2-3CF and can serve as another reliable alternative
      for C2PS instrumentation. Preoperative evaluation of pedicle trajectory of C2-3CF
      with three-dimensional CT is highly valuable in the choice of proper fixation
      methods.

PMID- 24894410
TI  - Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER
      trial) - study protocol for a randomized controlled trial.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive
      malignancies with marked resistance to chemo- and radiotherapy. PDA-cancer stem
      cells (CSCs) are not targeted by current therapies and may be a reason for poor
      prognosis. Studies indicate that diets rich in cabbage, broccoli, and cauliflower
      offer cancer preventative and therapeutic benefits. Recent experimental studies
      have confirmed these findings and demonstrated that isothiocyanate, sulforaphane,
      and the polyphenol, quercetin, effectively reduced tumor growth and enhanced the
      sensitivity of the cancer cells to current chemotherapeutics. The aim of the
      present study is to test the feasibility of a randomized controlled trial on the
      application of freeze-dried broccoli sprouts in patients with advanced PDA.
      METHODS AND STUDY DESIGN: The study is designed as a prospective randomized,
      double-blinded pilot trial with a treatment and a placebo-controlled arm in a
      single center setting. A total number of forty patients (18 years or older) in
      two parallel groups with advanced, surgically non-resectable PDA under palliative
      chemotherapy are planned for recruitment. Patients in the treatment group will
      receive fifteen capsules of the study substance per day (90 mg of active
      sulforaphane) during the chemotherapy treatment course. Patients in the placebo
      group will receive the same capsule size and portion distribution with inactive
      substances (mainly methylcellulose). The follow-up duration is one year.
      Feasibility of the study substance, adverse effects, and patient compliance, as
      well as levels of serum tumor markers (CEA, CA 19-9), quality of life, and
      patient overall survival rates will be assessed at defined points of time.
      DISCUSSION: The POUDER trial is expected to transfer promising experimental and
      epidemiological data into a clinical pilot study to assess the effectiveness of
      broccoli sprout extracts in the treatment of advanced PDA. The study objectives
      will provide data on the clinical feasibility and acceptability of a supportive
      treatment option accompanying palliative chemotherapy. Based on these results,
      future clinical studies to create further evidence in this field are possible.
      TRIAL REGISTRATION: The POUDER trial has been registered at ClinicalTrials.gov
      with an ID NCT01879878 and WHO with an ID U1111-1144-2013 on June 13th 2013.

PMID- 24894414
TI  - Welcome to EBEC 2014.

PMID- 24894413
TI  - Hematopoietic cell transplantation comorbidity index (HCT-CI) is predictive of
      adverse events and overall survival in older allogeneic transplant recipients.
AB  - OBJECTIVES: Our goal was to evaluate the ability of the hematopoietic cell
      transplantation comorbidity index (HCT-CI) to predict outcomes after allogeneic
      stem cell transplant (SCT) within the context of an older patient population,
      where multiple comorbidities are common. MATERIALS AND METHODS: We performed a
      retrospective cohort study of SCT patients >=50years of age at our institution,
      identifying 59 patients with complete HCT-CI data collected prospectively.
      RESULTS: HCT-CI category distribution in our sample was disproportionate, with
      almost half of patients having scores >=3. High HCT-CI score (>=3 vs <3) was
      associated with significantly inferior OS (median OS not reached for HCT-CI <3 vs
      14months for HCT-CI >=3; hazard ratio (HR) 2.2, p=0.02). HCT-CI score was a
      better predictor of OS than age, performance status or conditioning intensity.
      When adjusted for disease relapse risk, HCT-CI score conferred a worse prognosis
      in the low risk group (HR 1.43, p=0.03) but not in the intermediate/high risk
      group (HR 1.08, p=0.65). NRM was low in the total sample (6% at one year) and was
      not associated with HCT-CI score. Grade 3-4 non-hematologic adverse events within
      the first 100days after SCT were significantly more common in the higher HCT-CI
      groups (p=0.02). CONCLUSIONS: In our older patient cohort with a high incidence
      of multiple comorbidities, HCT-CI score >=3 was significantly associated with OS,
      particularly in the subset of patients with a low disease relapse risk.

PMID- 24894412
TI  - Magnetic tweezers for the measurement of twist and torque.
AB  - Single-molecule techniques make it possible to investigate the behavior of
      individual biological molecules in solution in real time. These techniques
      include so-called force spectroscopy approaches such as atomic force microscopy,
      optical tweezers, flow stretching, and magnetic tweezers. Amongst these
      approaches, magnetic tweezers have distinguished themselves by their ability to
      apply torque while maintaining a constant stretching force. Here, it is
      illustrated how such a "conventional" magnetic tweezers experimental
      configuration can, through a straightforward modification of its field
      configuration to minimize the magnitude of the transverse field, be adapted to
      measure the degree of twist in a biological molecule. The resulting configuration
      is termed the freely-orbiting magnetic tweezers. Additionally, it is shown how
      further modification of the field configuration can yield a transverse field with
      a magnitude intermediate between that of the "conventional" magnetic tweezers and
      the freely-orbiting magnetic tweezers, which makes it possible to directly
      measure the torque stored in a biological molecule. This configuration is termed
      the magnetic torque tweezers. The accompanying video explains in detail how the
      conversion of conventional magnetic tweezers into freely-orbiting magnetic
      tweezers and magnetic torque tweezers can be accomplished, and demonstrates the
      use of these techniques. These adaptations maintain all the strengths of
      conventional magnetic tweezers while greatly expanding the versatility of this
      powerful instrument. 

PMID- 24894415
TI  - Co-morbidities increase the risk of disability pension among MS patients: a
      population-based nationwide cohort study.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic and often disabling disease. In
      2005, 62% of the MS patients in Sweden aged 16-65 years were on disability
      pension. The objective of this study is to investigate whether the presence of
      common co-morbidities increase MS patients' risk for disability pension. METHODS:
      This population-based cohort study included 4 519 MS patients and 4 972 174 non
      MS patients who in 2005 were aged 17-64 years, lived in Sweden, and were not on
      disability pension. Patients with MS were identified in the nationwide in- and
      outpatient registers, while four different registers were used to construct three
      sets of measures of musculoskeletal, mental, and cardiovascular disorders. Time
      dependent proportional hazard models with a five-year follow up were performed,
      adjusting for socio-demographic factors. RESULTS: All studied disorders were
      elevated among MS patients, regardless of type of measure used. MS patients with
      mental disorders had a higher risk for disability pension than MS patients with
      no such co-morbidities. Moreover, mental disorders had a synergistic influence on
      MS patients' risk for disability pension. These findings were also confirmed when
      conducting sensitivity analyses. Musculoskeletal disorders appeared to increase
      MS patients' risk for disability pension. The results with regard to
      musculoskeletal disorders' synergistic influence on disability pension were
      however inconclusive. Cardiovascular co-morbidity had no significant influence on
      MS-patients' risk for disability pension. CONCLUSIONS: Co-morbidities, especially
      mental disorders, significantly contribute to MS patients' risk of disability
      pension, a finding of relevance for MS management and treatment.

PMID- 24894417
TI  - Funding based on needs? A study on the use of needs assessment data by a major
      humanitarian health assistance donor in its decisions to allocate funds.
AB  - BACKGROUND: International humanitarian assistance is essential for disaster
      affected populations, particularly in resource scarce settings. To target such
      assistance, needs assessments are required. According to internationally endorsed
      principles, donor governments should provide funding for humanitarian assistance
      based on need. AIM: The aim of this study is to explore a major donor's use of
      needs assessment data in decision-making for allocations of funds for health
      related humanitarian assistance contributions. SETTING: This is a case study of
      the Swedish International Development Cooperation Agency (Sida), a major and
      respected international donor of humanitarian assistance. METHODS: To explore
      Sida's use of needs assessment data in practice for needs-based allocations, we
      reviewed all decision documents and assessment memoranda for humanitarian
      assistance contributions for 2012 using content analysis; this was followed by
      interviews with key personnel at Sida. RESULTS: Our document analysis found that
      needs assessment data was not systematically included in Sida's assessment
      memoranda and decision documents. In the interviews, we observed various
      descriptions of the concept of needs assessments, the importance of contextual
      influences as well as previous collaborations with implementing humanitarian
      assistance organizations. Our findings indicate that policies guiding funding
      decisions on humanitarian assistance need to be matched with available needs
      assessment data and that terminologies and concepts have to be clearly defined.
      CONCLUSION: Based on the document analysis and the interviews, it is unclear how
      well Sida used needs assessment data for decisions to allocate funds. However,
      although our observations show that needs assessments are seldom used in decision
      making, Sida's use of needs assessments has improved compared to a previous
      study. To improve project funds allocations based on needs assessment data, it
      will be critical to develop distinct frameworks for allocation distributions
      based on needs assessment and clear definitions, measurements and interpretations
      of needs. Key words: Needs assessment, humanitarian assistance, disasters, donor
      decision-making.

PMID- 24894420
TI  - Case report of intestinal tuberculosis 6 years after simultaneous pancreas and
      kidney transplant.
AB  - Tuberculosis (TB) is often difficult to diagnose in immunocompromised patients
      and occurs 20 to 74 times more frequently in recipients of solid organ
      transplants than in the general population. We present the case of a 40-year-old
      female immigrant from Mexico previously treated for latent TB who underwent a
      simultaneous pancreas and kidney transplant. She experienced 3 episodes of
      rejection and then presented with 4 months of nonspecific abdominal pain. She was
      ultimately diagnosed with disseminated TB presenting with intestinal perforation
      and pulmonary involvement. This case illustrates the need for clinicians to
      maintain a high index of suspicion for TB in transplant recipients, especially
      those previously treated for TB or rejection. 

PMID- 24894416
TI  - Lack of association of acute phase response proteins with hormone levels and
      antidepressant medication in perimenopausal depression.
AB  - BACKGROUND: Major depression is associated with higher plasma levels of positive
      acute-phase proteins, as well as with lower plasma levels of negative acute-phase
      proteins. The aim of this study is to examine the levels of acute-phase response
      proteins and whether these levels are influenced by reproductive hormones and
      antidepressant medication in the perimenopausal depression. METHODS: Sixty-five
      women (age range: 40-58 years old) participated in this study. All women were in
      the perimenopausal phase. The diagnosis of depression was made through a
      psychiatric interview and with the aid of Hamilton Depression Rating Scale 17
      (HAM-D 17). The acute-phase response proteins, such as haptoglobin (HP),
      transferrine (TRf), alpha1-antitrypsin, complement protein 3 (C3), complement
      protein 4 (C4) and C-reactive protein (CRP) and the reproductive hormones, for
      example follicle-stimulating hormone (FSH), luteinizing hormone (LH) and
      estradiol (E2), were analyzed using standard laboratory methods. Pearson's
      correlations were applied to evaluate the relationship between acute-phase
      proteins and hormones. RESULTS: Perimenopausal women were divided into three
      groups. The first group consisted of normal controls, the second one involved
      depressed perimenopausal women, who were taking selective serotonin reuptake
      inhibitors (SSRIs), and the third one included depressed women that were not
      treated with SSRIs. Depressed women in perimenopause, when being compared to non
      depressed women, did not differ as to serum levels of acute-phase proteins. There
      was a positive correlation between HP and E2 in depressed perimenopausal women,
      who were not taking SSRIs. CONCLUSIONS: The lack of association between acute
      phase proteins and depressive mood mentioned in this study does not support
      previous findings in patients with major depression. This negative finding in
      perimenopausal depression indicates either the absence or a more complex nature
      of the interactions between acute-phase proteins, low-grade inflammation and
      depression. The hormonal profile of women is a part of this complexity, because
      it seems that in perimenopause the hormonal changes are accompanied by changes of
      acute-phase response proteins. Particularly, in perimenopausal depression, there
      is an interaction between HP and E2. Therefore, it seems that perimenopause is a
      period of a woman's life during which hormonal, immune and metabolic changes
      occur and interact with each other making women vulnerable to depression.

PMID- 24894419
TI  - Remarkable increase in fluoroquinolone-resistant Mycoplasma genitalium in Japan.
AB  - OBJECTIVES: We determined the prevalence of macrolide and fluoroquinolone
      resistance-associated mutations in Mycoplasma genitalium DNA specimens from men
      with non-gonococcal urethritis (NGU) and analysed their effects on antibiotic
      treatments of M. genitalium infections. METHODS: In this retrospective study, we
      examined antibiotic resistance-associated mutations in the 23S rRNA, gyrA and
      parC genes of M. genitalium and the association of the mutations with
      microbiological outcomes of antibiotic treatments in men with M. genitalium
      positive NGU. RESULTS: No macrolide resistance-associated mutations in the 23S
      rRNA gene were observed in 27 M. genitalium DNA specimens in 2011 and in 24 in
      2012. However, 5 of 17 in 2013 had 23S rRNA mutations. Three of 15 in 2011, 6 of
      19 in 2012 and 8 of 17 in 2013 had fluoroquinolone resistance-associated
      alterations in ParC. Three in 2013 had both the antibiotic resistance-associated
      alterations coincidentally. In two men with M. genitalium harbouring 23S rRNA
      mutations, the mycoplasma persisted after treatment with a regimen of 2 g of
      extended-release azithromycin (AZM-SR) once daily for 1 day. All nine men with
      mycoplasma harbouring ParC alterations were microbiologically cured with a
      regimen of 100 mg of sitafloxacin twice daily for 7 days. CONCLUSIONS: Macrolide-
      or fluoroquinolone-resistant M. genitalium appears to be increasing, and the
      increase in fluoroquinolone-resistant mycoplasmas is especially remarkable in
      Japan. Mycoplasmas harbouring 23S rRNA mutations would be resistant to the AZM-SR
      regimen, but those harbouring ParC alterations would still be susceptible to the
      sitafloxacin regimen.

PMID- 24894421
TI  - Medication associated with hearing loss: 25 years of medical malpractice cases in
      the United States.
AB  - OBJECTIVES: Many medications have the potential for ototoxicity. To potentiate
      management of this risk, this study examines malpractice litigation trends of
      lawsuits involving hearing loss associated with medication use. As experts in
      hearing loss, it may benefit otolaryngologists to be familiar with this
      information. STUDY DESIGN: Retrospective review. SETTING: All US civil trials.
      SUBJECTS AND METHODS: Court records of legal trials from 1987 to 2012 were
      obtained from 2 major computerized databases. Data were compiled on the
      demographics of the defendant and plaintiff, use of otolaryngologists as expert
      witnesses, medication used, legal allegations, verdicts, and judgments. RESULTS:
      Forty-six unique cases met inclusion criteria and were selected for review.
      Antibiotics (72%), specifically aminoglycosides (47%), were the most common
      medications cited as causing hearing loss. Eleven (22%) cases were resolved
      through a settlement before a verdict was reached. Verdicts in favor of the
      plaintiffs (37%) were awarded an average of $1,134,242. Pediatric patients were
      more likely to have outcomes in their favor (P = .03) compared to adults. Of the
      cases found in favor of the plaintiff, the most common reasons cited were
      inappropriate medication, dose, or duration (59%); failure to properly monitor
      (39%); and failure to choose a less toxic medication (18%). CONCLUSIONS:
      Physicians must be aware of the potential effects of the medications they
      prescribe. An understanding of potential drug interactions, proper monitoring,
      and appropriate substitution with less toxic medications are important to improve
      patient care. Analyzing litigation trends may be used to prevent future lawsuits
      and improve physician awareness.

PMID- 24894422
TI  - Success of salvage treatment: a critical appraisal of salvage rates for different
      subsites of HNSCC.
AB  - OBJECTIVE: Despite advances in interdisciplinary treatment protocols, the chance
      of cure for recurrent head and neck squamous cell carcinoma (HNSCC) following
      failed primary therapy is poor and often entails a high morbidity. Recurrence
      rates vary widely in the literature depending on tumor localization, primary
      tumor stage, and treatment modality, and only a minority of patients can be
      salvaged. STUDY DESIGN: Historical cohort study. SETTING: This study valuates the
      outcomes of patients treated for recurrent squamous cell carcinoma of the larynx,
      pharynx, and oral cavity in the largest tertiary referral center of Switzerland
      to find predictors for survival in salvage surgery with curative intent. SUBJECTS
      AND METHODS: Included were 176 consecutive patients with recurrent disease after
      primary curative treatment of HNSCC, in locations mentioned previously. Kaplan
      Meier survival analyses with log-rank testing were performed depending on T and N
      stage, gender, treatment, and location of first relapse to evaluate the impact on
      overall survival, disease specific survival, and recurrence free survival.
      RESULTS: Overall successful salvage rates were 49.2% for laryngeal recurrence,
      35.1% for oral cavity, 32.7% for oropharyngeal, and a mere 17.4% for
      hypopharyngeal recurrences. Predictive factors for better outcome were location
      of recurrence, female gender, lymph node status, and extent of salvage treatment.
      CONCLUSION: In case of recurrent disease, laryngeal cancers showed the best
      salvage rates, whereas in hypopharyngeal relapses, very few patients could be
      successfully salvaged. Patients therefore should be carefully selected and
      counseled for salvage treatment according to patient motivation, age, type of
      previous treatment, surgical resectability, and exclusion of distant recurrence.

PMID- 24894423
TI  - Elective lymphadenectomy during salvage for locally recurrent head and neck
      squamous cell carcinoma after radiation.
AB  - OBJECTIVE: This study aimed to assess the rate of occult metastases in patients
      with head and neck mucosal squamous cell carcinoma who have undergone therapeutic
      neck radiation, and then develop primary site recurrence, without clinical
      evidence of recurrent neck disease. STUDY DESIGN: Case series with chart review.
      SETTING: Tertiary care center. SUBJECTS AND METHODS: Head and neck mucosal
      squamous cell carcinoma patients with N+ necks treated with primary radiation who
      developed primary site recurrence with radiologically resolved neck
      lymphadenopathy, treated with salvage primary-site surgery with or without
      elective cervical lymphadenectomy (ECL). Main outcome measures were rate of
      occult nodal metastases, complication rates, and disease-free survival. RESULTS:
      Sixteen patients met inclusion criteria. Of 18 neck sides that underwent either
      ECL or observation for a mean follow-up of 26 months, 4 (22.2%) were found to
      have positive occult cervical metastases, all on the ipsilateral side of
      preradiation neck disease. Patients with advanced T-stage and/or free flap
      reconstruction were more likely to undergo cervical lymphadenectomy. Patients
      with persistent (as opposed to recurrent) primary site tumors had the highest
      rate of occult cervical metastases. CONCLUSION: The risk of occult nodal
      metastases of 22.2%, in this study, may be too high to justify routinely omitting
      elective cervical lymphadenectomy in this patient population. Lymphadenectomy
      should especially be considered in patients with persistent tumors, with advanced
      recurrent T-stage, and undergoing free flap reconstruction.

PMID- 24894424
TI  - Compliance with recommendations for tympanostomy tube follow-up: patient
      characteristics.
AB  - OBJECTIVES: (1) To determine the percentage of otherwise healthy patients
      achieving "graduation," or postoperative compliance achieving complete problem
      resolution and discharge from the otolaryngologist's care, after tympanostomy
      tube placement. (2) To analyze follow-up behaviors and patient characteristics
      influencing the likelihood of graduation. STUDY DESIGN: Retrospective cohort
      study. SETTING: Tertiary care hospital. SUBJECTS AND METHODS: Analysis of details
      of tympanostomy tube placements performed from 2004 to 2011 by 2 pediatric
      otolaryngologists for children aged 0 to 18 years. Exclusion criteria were
      clearly defined craniofacial anomalies, cleft palates, and other ongoing
      postoperative care. The remaining study subjects were categorized into 3 groups.
      Graduation (GRAD) subjects achieved discharge from care with "follow-up pro re
      nata" status. LOST<2Y subjects had not attended scheduled follow-up in <2 years.
      LOST>=2Y subjects had no follow-up in >=2 years. RESULTS: A total of 1454
      pediatric subjects were included. GRADs constituted only 25.6% of the subject
      pool; 22.1% were LOST<2Y, and 52.3% were LOST>=2Y. Statistically significant
      factors in achieving graduation were total number of follow-up visits, total
      duration of follow-up, compliance with first postoperative visit, patient age,
      insurance type, and distance between home and practice. CONCLUSION: Rate of
      graduation, or postoperative compliance achieving complete problem resolution, of
      otherwise healthy tympanostomy tube patients is low despite perioperative
      discussions of the importance of proper follow-up. Higher graduation rates are
      associated with increasing number of follow-up visits and duration, younger
      patient age, private insurance, and proximity to the practice. Compliance with
      attending the first postoperative visit may be an early marker for increased
      likelihood of graduation.

PMID- 24894426
TI  - NFAT1 transcription factor in dendritic cells is required to modulate T helper
      cell differentiation.
AB  - The NFAT family of transcription factors plays a central role in the regulation
      of cytokine gene expression during the immune response. NFAT functions have been
      extensively explored in lymphocyte activation and differentiation, but the
      involvement of NFAT proteins in dendritic cells (DCs) is still not well known.
      Here, we investigated the role of the NFAT1 transcription factor in murine DCs.
      Initially, we demonstrated by western blot that the NFAT1 protein is present in
      splenic DCs and is rapidly activated upon calcium influx. We then used NFAT1
      deficient mice (NFAT1-/-) to investigate whether NFAT1 influences the ability of
      DCs to induce Th differentiation. Our data demonstrated that NFAT1-/- DCs showed
      an increased capacity to differentiate CD4 T cells to the Th1 phenotype. CD4
      cells that were primed in vitro with NFAT1-/- DCs had increased IFN-gamma
      production. The same results were observed when the CD4 cells were primed in vivo
      through the sensitization of NFAT1-/- mice with ovalbumin. Furthermore, our
      results demonstrated that the cytokine IL-12 is one of the factors involved in
      this process because its production is increased in NFAT1-/- mice, and
      neutralizing anti-IL-12 antibodies almost completely eliminated the IFN-gamma
      production. These results demonstrated that the NFAT1 transcription factor
      regulates specific functions in DCs that are involved in CD4 differentiation,
      suggesting that the inhibition of NFAT1 in DCs may be used as a therapy to
      modulate specific immune responses.

PMID- 24894425
TI  - Stress symptoms and frequency of sexual intercourse among young women.
AB  - INTRODUCTION: We have previously documented the relationships between stress and
      depression symptoms and adolescent women's nonuse and misuse of condoms and other
      contraceptive methods and on their unintended pregnancy rates. AIM: Here, we
      examine relationships between mental health symptoms and another understudied
      adolescent reproductive health behavior-frequency of sexual intercourse. MAIN
      OUTCOME MEASURE: Our outcome was weekly sexual intercourse activity. METHODS: We
      used panel data from a longitudinal, population-based cohort study of 992 women
      ages 18-20. Weekly journals measured sociodemographic, relationship,
      reproductive, and mental health characteristics, sexual and contraceptive
      behaviors, and pregnancy history. We examined 27,130 surveys from 952 women
      during the first study year. Predictors of weekly sexual intercourse were
      moderate to severe stress (Perceived Stress Scale-4) and depression (Center for
      Epidemiologic Studies Depression Scale-5) symptoms measured at baseline.
      Multilevel, mixed-effects logistic regression models estimated the relationships
      between stress and depression symptoms and the weekly odds of sexual intercourse
      while adjusting for covariate fixed effects and random woman effects. RESULTS:
      Nearly a quarter of the sample had moderate to severe stress (23%) and depression
      (24%) symptoms at baseline. Women reported sexual intercourse in 36% of weeks.
      Proportions of sexually active weeks were higher among women with stress (43%)
      and depression (40%) compared with those without symptoms (35% and 35%,
      respectively; P values<0.001). Controlling for covariates, women with baseline
      stress symptoms had 1.6 times higher weekly odds of sexual intercourse compared
      with women without stress (adjusted odds ratio 1.6, confidence interval [1.1,
      2.5]; P=0.04). Depression symptoms were not associated with sexual intercourse
      frequency in adjusted models. CONCLUSIONS: Stress symptoms were positively
      associated with sexual intercourse frequency among these young women. Research
      and practice efforts are needed to identify effective sexual health promotion and
      risk-reduction strategies, including contraceptive education and counseling, in
      the context of mental health symptoms and unintended pregnancy.

PMID- 24894427
TI  - Mustard gas surrogate, 2-chloroethyl ethylsulfide (2-CEES), induces centrosome
      amplification and aneuploidy in human and mouse cells : 2-CEES induces centrosome
      amplification and chromosome instability.
AB  - Mustard gas is a simple molecule with a deadly past. First used as a chemical
      weapon in World War I, its simple formulation has raised concerns over its use by
      terrorist organizations and unstable governments. Mustard gas is a powerful
      vesicant and alkylating agent that causes painful blisters on epithelial surfaces
      and increases the incidence of cancer in those exposed. The mechanism of mustard
      gas toxicity and tumorigenesis is not well understood but is thought to be
      mediated by its ability to induce oxidative stress and DNA damage. Interestingly,
      several proteins that have been shown to either be targets of mustard gas or
      mediate mustard gas toxicity have also been shown to regulate centrosome
      duplication. Centrosomes are small nonmembrane-bound organelles that direct the
      segregation of chromosomes during mitosis through the formation of the bipolar
      mitotic spindle. Cells with more or less than two centrosomes during mitosis can
      segregate their chromosomes unequally, resulting in chromosome instability, a
      common phenotype of cancer cells. In our studies, we show that subtoxic levels of
      2-chloroethyl ethylsulfide (2-CEES), a mustard gas analog, induce centrosome
      amplification and chromosome instability in cells, which may hasten the mutation
      rate necessary for tumorigenesis. These data may explain why those exposed to
      mustard gas exhibit higher incidences of cancer than unexposed individuals of the
      same cohort. 

PMID- 24894429
TI  - Visual feedback-related changes in ipsilateral cortical excitability during
      unimanual movement: Implications for mirror therapy.
AB  - Provision of a mirror image of a hand undertaking a motor task (i.e., mirror
      therapy) elicits behavioural improvements in the inactive hand. A greater
      understanding of the neural mechanisms underpinning this phenomenon is required
      to maximise its potential for rehabilitation across the lifespan, e.g., following
      hemiparesis or unilateral weakness. Young and older participants performed
      unilateral finger abductions with no visual feedback, with feedback of the active
      or passive hands, or with a mirror image of the active hand. Transcranial
      magnetic stimulation was used to assess feedback-related changes in two
      neurophysiological measures thought to be involved in inter-manual transfer of
      skill, namely corticospinal excitability (CSE) and intracortical inhibition
      (SICI) in the passive hemisphere. Task performance led to CSE increases,
      accompanied by decreases of SICI, in all visual feedback conditions relative to
      rest. However, the changes due to mirror feedback were not significantly
      different to those observed in the other (more standard) visual conditions.
      Accordingly, the unimanual motor action itself, rather than modifications in
      visual feedback, appears more instrumental in driving changes in CSE and SICI.
      Therefore, changes in CSE and SICI are unlikely to underpin the behavioural
      benefits of mirror therapy. We discuss implications for rehabilitation and
      directions of future research. 

PMID- 24894428
TI  - Lung cancer is associated with decreased expression of perforin, granzyme B and
      interferon (IFN)-gamma by infiltrating lung tissue T cells, natural killer (NK) T
      like and NK cells.
AB  - There is a limited understanding how of lung cancer cells evade cytotoxic attack.
      Previously, we have shown reduced production of the cytotoxic mediator granzyme B
      by CD8(+) T cells in lung cancer tissue. We hypothesized that lung cancer would
      be further associated with decreased production of granzyme B, perforin and
      proinflammatory cytokines by other cytotoxic lymphocytes, natural killer (NK) T
      like and NK cells, and that this would result from soluble mediators released by
      the cancer cells. Lung cancer and non-cancer tissue from five patients was
      identified by experienced pathologists. Tumour necrosis factor (TNF)-alpha,
      interferon (IFN)-gamma, granzyme B and perforin were measured in CD4 and CD8(+)
      T, NK T-like cells and NK cells by flow cytometry. Correlation between cancer
      stage and granzyme B was analysed retrospectively for 21 patients. The effects of
      soluble factors released by lung cancer cells on production of cytotoxic
      mediators and cytokines was assessed, and the role of prostaglandin E2 (PGE)2
      /COX investigated using indomethacin inhibition. There were significantly
      decreased percentages of T, NK T-like and NK cells expressing perforin, TNF-alpha
      and IFN-gamma in cancer versus non-cancer tissue, and of CD8(+) T cells and
      CD8(+) NK T-like cells expressing granzyme B (e.g. NK T-like cells: non-cancer
      30% +/- 7 versus cancer 6% +/- 2.5). Cancer cells released soluble factors that
      inhibited granzyme B, perforin and IFN-gamma production that was partially
      associated with the PGE2 /COX2 pathway. Thus, lung cancer is associated with
      decreased expression of granzyme B, perforin and IFN-gamma by infiltrating T
      cells, NK T-like and NK cells, possibly as a result of soluble factors produced
      by the cancer cells including PGE2 . This may be an important immune evasion
      mechanism.

PMID- 24894430
TI  - Dietary patterns and the association with dietary quality among Mongolian
      immigrants in South Korea.
AB  - Mongolian immigration into South Korea has increased rapidly over the last
      decade. It is important to better understand dietary patterns of immigrants
      because these patterns are associated with health risk. This study aimed to
      characterize dietary patterns of Mongolian immigrants in South Korea. Dietary
      intakes of 500 Mongolian adults living in South Korea were assessed using the
      interviewer-administered 24-h dietary recall method. By cluster analysis, three
      dietary patterns were identified: "Mongolian" (26%), "Transitional" (43%) and
      "Korean" (31%). The "Korean" pattern had a favorable food intake profile, with
      higher intakes of healthy foods, while the other patterns had features of an
      unhealthy diet. There were significant differences between the dietary patterns
      that were related to risk for chronic diseases. Overall, subjects following the
      "Korean" dietary pattern showed high adherence to World Health Organization
      recommendations for preventing diet-related chronic diseases, whereas the
      "Mongolian" and "Transitional" patterns showed low compliance. The results
      suggest the need for education programs targeting Mongolian immigrants who retain
      traditional dietary habits, to enhance their healthy food choices.

PMID- 24894432
TI  - Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and
      deoxynivalenol in animals and humans: an update.
AB  - Trichothecenes are a large family of structurally related toxins mainly produced
      by Fusarium genus. Among the trichothecenes, T-2 toxin and deoxynivalenol (DON)
      cause the most concern due to their wide distribution and highly toxic nature.
      Trichothecenes are known for their inhibitory effect on eukaryotic protein
      synthesis, and oxidative stress is one of their most important underlying toxic
      mechanisms. They are able to generate free radicals, including reactive oxygen
      species, which induce lipid peroxidation leading to changes in membrane
      integrity, cellular redox signaling, and in the antioxidant status of the cells.
      The mitogen-activated protein kinases signaling pathway is induced by oxidative
      stress, which also induces caspase-mediated cellular apoptosis pathways. Several
      new metabolites and novel metabolic pathways of T-2 toxin have been discovered
      very recently. In human cell lines, HT-2 and neosolaniol (NEO) are the major
      metabolites of T-2 toxin. Hydroxylation on C-7 and C-9 are two novel metabolic
      pathways of T-2 toxin in rats. The metabolizing enzymes CYP3A22, CYP3A29, and
      CYP3A46 in pigs, as well as the enzymes CYP1A5 and CYP3A37 in chickens, are able
      to catalyze T-2 toxin and HT-2 toxin to form the C-3'-OH metabolites. Similarly
      to carboxylesterase, CYP3A29 possesses the hydrolytic ability in pigs to convert
      T-2 toxin to NEO. T-2 toxin is able to down- or upregulate cytochrome P-450
      enzymes in different species. The metabolism of DON in humans is region
      dependent. Free DON and DON-glucuronide are considered to be the biomarkers for
      humans. The masked mycotoxin DON-3-beta-D-glucoside can be hydrolyzed to free DON
      in the body. This review will provide useful information on the progress of
      oxidative stress as well as on the metabolism and the metabolizing enzymes of T-2
      toxin and DON. Moreover, the literature will throw light on the blind spots of
      metabolism and toxicological studies in trichothecenes that have to be explored
      in the future.

PMID- 24894433
TI  - Role of Klotho, an antiaging protein, in pulmonary fibrosis.
AB  - Klotho is a recently discovered antiaging protein. Although many researchers are
      investigating the roles of Klotho in chronic kidney diseases and cancer, however,
      there are no studies on the roles of Klotho in chronic pulmonary diseases. The
      purpose of this study was to define the role of Klotho in pulmonary fibrosis
      using a murine model of ovalbumin (OVA)-induced chronic asthma and in BEAS-2B
      human bronchial epithelial cells. In an in vivo experiment, mice were sensitized
      by intraperitoneal injection of OVA (20 MUg/mouse), followed 1 week later by an
      airway challenge with 1 % OVA solution delivered three times a week for 4 weeks.
      In an in vitro experiment, we investigated the effects of stimulated with
      interleukin (IL)-4 and tumor necrosis factor (TNF)-alpha on Klotho protein and
      VEGF and transforming growth factor (TGF)-beta1/Smad3 signaling in BEAS-2B cells.
      Klotho decreased and VEGF and TGF-beta1 levels increased with increasing duration
      of OVA challenge. Similar findings were found for the expression of these
      proteins in lung tissue. The collagen content in lung tissue increased with
      repeated OVA challenge. In the in vitro experiment, Klotho expression decreased
      and VEGF and TGF-beta1/Smad3 expression increased after IL-4 (50 ng/mL) and TNF
      alpha (50 ng/mL) stimulation. Pretreatment with 25, 50, and 100 ng/mL of Klotho
      protein significantly attenuated the increases in VEGF and TGF-beta1/Smad3
      expression levels after IL-4 and TNF-alpha treatment, and reduced alpha-smooth
      muscle actin expression in concentration-dependent manner. Klotho protein
      inhibited the fibrotic response by suppressing VEGF and TGF-beta1/Smad3
      expression. These results suggest that Klotho protein may be crucial to
      inhibiting fibrosis associated with chronic airway diseases.

PMID- 24894434
TI  - Perceptions towards lesbian, gay and bisexual people in residential care
      facilities: a qualitative study.
AB  - BACKGROUND: Internationally, increases in the numbers of older people will be
      reflected in larger numbers of more socioculturally diverse groups of older
      people requiring care provided by residential care facilities. Covert and overt
      instances of homophobia are evident within residential care services provided to
      older lesbian, gay and bisexual people. AIMS: To explore the perceptions of care
      staff working in residential care homes towards older lesbian, gay and bisexual
      people. DESIGN: Critical gerontology formed the methodological foundations for
      focus group discussions with care staff from seven residential care facilities.
      Hypothetical vignettes were used to stimulate discussion amongst participants.
      RESULTS: Thematic analysis of the seven focus group interviews illuminated three
      themes: 'Knowing me knowing you', 'Out of sight out of mind' and 'It's a
      generational thing'. Subtle as well as not so subtle forms of homophobia were
      evident in each of the themes. Care staff felt they were largely unprepared to
      provide care to older lesbian, gay and bisexual people. CONCLUSION: This small
      scale New Zealand study identifies that the residential care sector is not always
      supportive, or prepared, to provide a care service to those people identifying as
      lesbian, gay and bisexual. IMPLICATIONS FOR PRACTICE: Findings from this study
      recommend the implementation of principle-based guidelines, opportunities to
      participate in ongoing education and partnering with non-heterosexual community
      organisations in order to provide culturally appropriate care to older lesbian,
      gay and bisexual people.

PMID- 24894435
TI  - David Sowby.

PMID- 24894431
TI  - The optical, photothermal, and facile surface chemical properties of gold and
      silver nanoparticles in biodiagnostics, therapy, and drug delivery.
AB  - Nanotechnology is a rapidly growing area of research in part due to its
      integration into many biomedical applications. Within nanotechnology, gold and
      silver nanostructures are some of the most heavily utilized nanomaterial due to
      their unique optical, photothermal, and facile surface chemical properties. In
      this review, common colloid synthesis methods and biofunctionalization strategies
      of gold and silver nanostructures are highlighted. Their unique properties are
      also discussed in terms of their use in biodiagnostic, imaging, therapeutic, and
      drug delivery applications. Furthermore, relevant clinical applications utilizing
      gold and silver nanostructures are also presented. We also provide a table with
      reviews covering related topics.

PMID- 24894436
TI  - Peer volunteers in an integrative pain management program for frail older adults
      with chronic pain: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Chronic pain is common among the older population. A literature
      review on pain management program showed that exercise, yoga, massage therapy,
      Tai Chi, and music therapy could significantly reduce pain. In spite of the
      proven benefits of pain management programs, these intervention programs were
      effective only in the short term, and older adults would resume their old habits.
      It has been suggested that interventions comprising some type of social support
      have great potential to increase the participation of older adults. Therefore, we
      propose the inclusion of peer volunteers in an integrated pain management program
      to relieve pain among frail older adults. This study aims to explore the
      effectiveness of an integrated pain management program supplemented with peer
      volunteers in improving pain intensity, functional mobility, physical activity,
      loneliness levels, happiness levels, and the use of non-pharmacological pain
      relieving methods among frail older adults with chronic pain. METHODS/DESIGN: We
      intend to recruit 30 nursing home residents and 30 peer volunteers from the
      Institute of Active Ageing in Hong Kong in a group trial for an 8-week group
      based integrated pain management program. There will be 16 sessions, with two 1
      hour sessions each week.The primary outcome will be pain levels, while secondary
      outcomes will be assessed according to functional mobility, physical activity,
      loneliness levels, happiness levels, the use of non-pharmacological pain
      relieving methods, and through a questionnaire for volunteers. DISCUSSION: In
      view of the high prevalence of chronic pain among older adults and its adverse
      impacts, it is important to provide older adults with tools to control their
      pain. We propose the use of peer volunteers to enhance the effects of an
      integrated pain management program. It is expected that pain can be reduced and
      improvements can be achieved among older adults in the areas of physical
      activity, functional mobility, loneliness levels, happiness levels, and the use
      of non-pharmacological pain relieving methods. Using these results, we will
      assess the need to conduct a larger study with a randomized controlled design.
      TRIAL REGISTRATION: This trial was registered on 24 February 2014 at the
      Australian New Zealand Clinical Trials Registry (ANZCTR) with the trial number:
      ACTRN12614000195651.

PMID- 24894437
TI  - Risk factors for bovine mastitis in the Central Province of Sri Lanka.
AB  - A study of the risk factors associated with mastitis in Sri Lankan dairy cattle
      was conducted to inform risk reduction activities to improve the quality and
      quantity of milk production and dairy farmer income. A cross-sectional survey of
      randomly selected dairy farms was undertaken to investigate 12 cow and 39 herd
      level and management risk factors in the Central Province. The farm level
      prevalence of mastitis (clinical and subclinical) was 48 %, similar to what has
      been found elsewhere in South and Southeast Asia. Five cow level variables, three
      herd level variables, and eight management variables remained significant (p <
      0.05) in the final logistic regression analysis. Expected risk factors relating
      to unhygienic environments and inadequate knowledge or practice of mastitis
      control were found. Other factors included parity, milk yield, milking practices,
      access to veterinary services, use of veterinary products, stall structure, and
      stall hygiene. Many of the risk factors could be addressed by standard dairy
      cattle management techniques, but implementation of mastitis control programs as
      a technical approach is likely to be insufficient to achieve sustainable disease
      control without consideration of the social and political realities of
      smallholder farmers, who are often impoverished. 

PMID- 24894438
TI  - High doses of highly pathogenic avian influenza virus in chicken meat are
      required to infect ferrets.
AB  - High pathogenicity avian influenza viruses (HPAIV) have caused fatal infections
      in mammals through consumption of infected bird carcasses or meat, but scarce
      information exists on the dose of virus required and the diversity of HPAIV
      subtypes involved. Ferrets were exposed to different HPAIV (H5 and H7 subtypes)
      through consumption of infected chicken meat. The dose of virus needed to infect
      ferrets through consumption was much higher than via respiratory exposure and
      varied with the virus strain. In addition, H5N1 HPAIV produced higher titers in
      the meat of infected chickens and more easily infected ferrets than the H7N3 or
      H7N7 HPAIV.

PMID- 24894439
TI  - A method to make a craniotomy on the ventral skull of neonate rodents.
AB  - The use of a craniotomy for in vivo experiments provides an opportunity to
      investigate the dynamics of diverse cellular processes in the mammalian brain in
      adulthood and during development. Although most in vivo approaches use a
      craniotomy to study brain regions located on the dorsal side, brainstem regions
      such as the pons, located on the ventral side remain relatively understudied. The
      main goal of this protocol is to facilitate access to ventral brainstem
      structures so that they can be studied in vivo using electrophysiological and
      imaging methods. This approach allows study of structural changes in long-range
      axons, patterns of electrical activity in single and ensembles of cells, and
      changes in blood brain barrier permeability in neonate animals. Although this
      protocol has been used mostly to study the auditory brainstem in neonate rats, it
      can easily be adapted for studies in other rodent species such as neonate mice,
      adult rodents and other brainstem regions. 

PMID- 24894440
TI  - The impact of receptor-receptor interactions in heteroreceptor complexes on brain
      plasticity.
AB  - Allosteric mechanisms in receptor heteromers markedly increase the repertoire of
      receptor recognition and signaling. Of high importance is the altered function in
      the receptor heteromer versus the receptor homomer. Such a change in receptor
      function is mainly brought about by agonist induced allosteric receptor-receptor
      interactions and leads to functional and structural plasticity. Receptor-receptor
      interactions integrating synaptic and volume transmission signals participate in
      a significant way in modulating bidirectional synaptic plasticity and thus
      Hebbian plasticity. One molecular mechanism that can contribute to a change of
      synaptic weight may be represented by multiple interactions between plasma
      membrane receptors forming higher order heteroreceptor complexes via
      oligomerization at the pre- and post-junctional level. Such long-lived
      heteroreceptor complexes may play a significant role in learning and memory. 

PMID- 24894441
TI  - Significance of vitamin d receptor gene polymorphisms for risk of hepatocellular
      carcinoma in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Biological and epidemiological data suggest that vitamin D
      levels may influence cancer development. Several single nucleotide polymorphisms
      have been described in the vitamin D receptor (VDR) gene in association with
      cancer risk. We aimed to investigate the association of VDR gene polymorphisms
      with hepatocellular carcinoma (HCC) development in chronic hepatitis C patients.
      METHODS: In a cross-sectional, hospital-based setting, 340 patients (201 chronic
      hepatitis, 47 cirrhosis and 92 HCC) and 100 healthy controls receiving VDR
      genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 C and TaqI rs731236
      A) were enrolled. RESULTS: Patients with HCC had a higher frequency of ApaI CC
      genotype (P = 0.027) and bAt[CCA]-haplotype (P = 0.037) as compared to control
      subjects. There were no differences in BsmI and TaqI polymorphisms between two
      groups. In patients with chronic hepatitis C, HCC subjects had a higher frequency
      of ApaI CC genotype and bAt[CCA]-haplotype than those with chronic hepatitis (P =
      0.001 and 0.002, respectively) and cirrhosis (P = 0.019 and 0.026, respectively).
      After adjusting age and sex, logistic regression analysis showed that ApaI CC
      genotype (odds ratio: 3.02, 95% confident interval: 1.65-5.51) was independently
      associated with HCC development. CONCLUSION: VDR ApaI polymorphism plays a role
      in the development of HCC among chronic hepatitis C patients. Further
      explorations of this finding and its implications are required.

PMID- 24894443
TI  - Chelation therapy in intoxications with mercury, lead and copper.
AB  - In the present review we provide an update of the appropriate use of chelating
      agents in the treatment of intoxications with compounds of mercury, lead and
      copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and
      2,3-dimercapto-propanesulphonate (DMPS) can effectively mobilize deposits of
      mercury as well as of lead into the urine. These drugs can be administered orally
      and have relatively low toxicity compared to the classical antidote
      dimercaptopropanol (BAL). d-Penicillamine has been widely used in copper
      overload, although 2,3-dimercaptosuccinic acid or tetrathiomolybdate may be more
      suitable alternatives today. In copper-toxicity, a free radical scavenger might
      be recommended as adjuvant to the chelator therapy. 

PMID- 24894442
TI  - Uptake and toxicity of arsenite and arsenate in cultured brain astrocytes.
AB  - Inorganic arsenicals are environmental toxins that have been connected with
      neuropathies and impaired cognitive functions. To investigate whether such
      substances accumulate in brain astrocytes and affect their viability and
      glutathione metabolism, we have exposed cultured primary astrocytes to arsenite
      or arsenate. Both arsenicals compromised the cell viability of astrocytes in a
      time- and concentration-dependent manner. However, the early onset of cell
      toxicity in arsenite-treated astrocytes revealed the higher toxic potential of
      arsenite compared with arsenate. The concentrations of arsenite and arsenate that
      caused within 24h half-maximal release of the cytosolic enzyme lactate
      dehydrogenase were around 0.3mM and 10mM, respectively. The cellular arsenic
      contents of astrocytes increased rapidly upon exposure to arsenite or arsenate
      and reached after 4h of incubation almost constant steady state levels. These
      levels were about 3-times higher in astrocytes that had been exposed to a given
      concentration of arsenite compared with the respective arsenate condition.
      Analysis of the intracellular arsenic species revealed that almost exclusively
      arsenite was present in viable astrocytes that had been exposed to either
      arsenate or arsenite. The emerging toxicity of arsenite 4h after exposure was
      accompanied by a loss in cellular total glutathione and by an increase in the
      cellular glutathione disulfide content. These data suggest that the high arsenite
      content of astrocytes that had been exposed to inorganic arsenicals causes an
      increase in the ratio of glutathione disulfide to glutathione which contributes
      to the toxic potential of these substances. 

PMID- 24894444
TI  - Two methods for establishing primary human endometrial stromal cells from
      hysterectomy specimens.
AB  - Many efforts have been devoted to establish in vitro cell culture systems. These
      systems are designed to model a vast number of in vivo processes. Cell culture
      systems arising from human endometrial samples are no exception. Applications
      range from normal cyclic physiological processes to endometrial pathologies such
      as gynecological cancers, infectious diseases, and reproductive deficiencies.
      Here, we provide two methods for establishing primary endometrial stromal cells
      from surgically resected endometrial hysterectomy specimens. The first method is
      referred to as "the scraping method" and incorporates mechanical scraping using
      surgical or razor blades whereas the second method is termed "the trypsin
      method." This latter method uses the enzymatic activity of trypsin to promote the
      separation of cells and primary cell outgrowth. We illustrate step-by-step
      methodology through digital images and microscopy. We also provide examples for
      validating endometrial stromal cell lines via quantitative real time polymerase
      chain reactions (qPCR) and immunofluorescence (IF). 

PMID- 24894445
TI  - MRI analysis of coracohumeral interval width and its relation to rotator cuff
      tear.
AB  - OBJECTIVE: Coracoid impingement is an uncommon cause of the shoulder pain. It is
      stimulated by adduction, internal rotation and forward flexion. These positions
      decrease the width of the coracohumeral interval. Owing to restriction of
      movement, rotator cuff tendons may be overloaded. Thus, in this study, we aimed
      to determine whether coracoid impingement increase the tendency of rotator cuff
      tears. MATERIALS AND METHODS: Routine clinical MRI sequences of 117 shoulders
      were reviewed, and axial coracohumeral interval measurements were taken. Rotator
      cuff tendon integrity was evaluated. Relation between rotator cuff tear and
      coracohumeral interval width was commented statically. RESULTS: Seventy-nine of
      the patients were women, 38 of them men. The average age was 44.8 +/- 14.2 (14
      75). The mean age of patients with rotator cuff tear was significantly higher
      than patients without tear (p = 0.001). The mean value of coracohumeral interval
      width was 8.853 +/- 2.491 mm (min: 2.9-max: 15.8). There were no significant
      differences between coracohumeral interval width of women and men (p = 0.139).
      The mean value of coracohumeral interval width with rotator cuff tear was 8.362
      +/- 2.382, and without tear was 9.351 +/- 2.520. There was a significant
      differences between them (p = 0.031). CONCLUSION: According to our study, there
      was a relationship between coracohumeral interval width and rotator cuff tear, so
      decreasing coracohumeral interval width may increase tendency of rotator cuff
      tear.

PMID- 24894446
TI  - A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with
      dominant inheritance.
AB  - BACKGROUND: Charcot-Marie-Tooth disease (CMT) refers to a heterogeneous group of
      genetic motor and sensory neuropathies. According to the primary site of damage,
      a distinction is made between demyelinating and axonal forms (CMT1 and 2,
      respectively, when inherited as an autosomal dominant trait). Leucine-rich repeat
      and sterile alpha motif-containing protein 1 (LRSAM1) is a ubiquitin-protein
      ligase with a role in sorting internalised cell-surface receptor proteins. So
      far, mutations in the LRSAM1 gene have been shown to cause axonal CMT in three
      different families and can confer either dominant or recessive transmission of
      the disease. CASE PRESENTATION: We have identified a novel mutation in LRSAM1 in
      a small family with dominant axonal CMT. Electrophysiological studies show
      evidence of a sensory axonal neuropathy and are interesting in so far as giant
      motor unit action potentials (MUAPs) are present on needle electromyography
      (EMG), while motor nerve conduction studies including compound motor action
      potential (CMAP) amplitudes are completely normal. The underlying mutation
      c.2046+1G >T results in the loss of a splice donor site and the inclusion of 63
      additional base pairs of intronic DNA into the aberrantly spliced transcript.
      This disrupts the catalytically active RING (Really Interesting New Gene) domain
      of LRSAM1. CONCLUSIONS: Our findings suggest that, beyond the typical length
      dependent degeneration of motor axons, damage of cell bodies in the anterior horn
      might play a role in LRSAM1-associated neuropathies. Moreover, in conjunction
      with other data in the literature, our results support a model, by which
      disruption of the C-terminal RING domain confers dominant negative properties to
      LRSAM1.

PMID- 24894447
TI  - Synergistic integration of ion-exchange and catalytic reduction for complete
      decomposition of perchlorate in waste water.
AB  - Ion-exchange has been frequently used for the treatment of perchlorate (ClO4(-)),
      but disposal or regeneration of the spent resins has been the major hurdle for
      field application. Here we demonstrate a synergistic integration of ion-exchange
      and catalytic decomposition by using Pd-supported ion-exchange resin as an
      adsorption/catalysis bifunctional material. The ion-exchange capability of the
      resin did not change after generation of the Pd clusters via mild ethanol
      reduction, and thus showed very high ion-exchange selectivity and capacity toward
      ClO4(-). After the resin was saturated with ClO4(-) in an adsorption mode, it was
      possible to fully decompose the adsorbed ClO4(-) into nontoxic Cl(-) by the
      catalytic function of the Pd catalysts under H2 atmosphere. It was demonstrated
      that prewetting the ion-exchange resin with ethanol significantly accelerate the
      decomposition of ClO4(-) due to the weaker association of ClO4(-) with the ion
      exchange sites of the resin, which allows more facile access of ClO4(-) to the
      catalytically active Pd-resin interface. In the presence of ethanol, >90% of the
      adsorbed ClO4(-) could be decomposed within 24 h at 10 bar H2 and 373 K. The
      ClO4(-) adsorption-catalytic decomposition cycle could be repeated up to five
      times without loss of ClO4(-) adsorption capacity and selectivity. 

PMID- 24894450
TI  - Public health risk communication by text message in response to a cluster of
      invasive meningococcal infection in a primary school.
AB  - Public health risk communication during emergencies should be rapid and accurate
      in order to allow the audience to take steps to prevent adverse outcomes. Delays
      to official communications may cause unnecessary anxiety due to uncertainty or
      inaccurate information circulating within the at-risk group. Modern electronic
      communications present opportunities for rapid, targeted public health risk
      communication. We present a case report of a cluster of invasive meningococcal
      disease in a primary school in which we used the school's mass short message
      service (SMS) text message system to inform parents and guardians of pupils about
      the incident, to tell them that chemoprophylaxis would be offered to all pupils
      and staff, and to advise them when to attend the school to obtain further
      information and antibiotics. Following notification to public health on a
      Saturday, an incident team met on Sunday, sent the SMS messages that afternoon,
      and administered chemoprophyaxis to 93% of 404 pupils on Monday. The use of mass
      SMS messages enabled rapid communication from an official source and greatly
      aided the public health response to the cluster. 

PMID- 24894449
TI  - Associations between impulsivity, aggression, and suicide in Chinese college
      students.
AB  - BACKGROUND: Although there are accumulating data regarding the epidemiology of
      suicide in China, there are meager data on suicidal ideation and attempts among
      college students. Interestingly, elevated impulsivity is thought to facilitate
      the transition from suicidal thoughts to suicidal behavior. Therefore, the
      objective of this research was to identify the associations between suicide and
      the personality factors of impulsivity and aggression. METHODS: This study's
      sampling method employed stratified random cluster sampling. A multi-stage
      stratified sampling procedure was used to select participants (n = 5,245). We
      conducted structured interviews regarding a range of socio-demographic
      characteristics and suicidal morbidity. The Patient Health Questionnaire
      depression module (PHQ-9) was used to acquire the information about thoughts of
      being better off dead or hurting themselves in some ways during the past two
      weeks. The impulsivity symptoms in this study were assessed with the BIS-11-CH
      (i.e., the Chinese version of the BIS-11), and the Aggressive symptoms were
      assessed with the BAQ. The statistical package for social science (SPSS) v.13.0
      program (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Socio
      demographic variables such as ethnic and gender were compared between groups,
      through the use of chi2 tests. The nonparametric test (k Independent Sample test,
      Kruskal-Wallis H) was performed to determine differences between the personality
      factors of impulsivity and aggression and suicide. RESULTS: In total, 9.1% (n =
      479) of the 5,245 students reported they have ever thought about committing
      suicide; and 1% (n = 51) reported a history of attempted suicide (attempters).
      The analyses detected significant differences in scores on cognitive impulsivity
      (p < 0.01), when comparing individuals who only had suicidal ideation and
      individuals who had attempted suicide. Moreover, significant differences were
      found between ideators only and attempters on scores of self-oriented attack (p <
      .001). CONCLUSIONS: Suicidal ideation is prevalent among Chinese university
      students. Students with high aggression scores were more susceptible to
      committing suicide. Scores on self-oriented attack and cognitive impulsivity may
      be important factors for differentially predicting suicide ideation and suicide
      attempts.

PMID- 24894451
TI  - Part 1: Laboratory culture of Centroptilum triangulifer (Ephemeroptera: Baetidae)
      using a defined diet of three diatoms.
AB  - Development of methods for assessing exposure and effects of waterborne toxicants
      on stream invertebrate species is important to elucidate environmentally relevant
      information. Current protocols for freshwater invertebrate toxicity testing
      almost exclusively utilize cladocerans, amphipods or chironomids rather than the
      more typical aquatic insect taxa found in lotic systems. Centroptilum
      triangulifer is a parthenogenetic mayfly occurring in depositional habitats of
      streams and rivers of the Eastern U.S. and Canada. C. triangulifer is an ideal
      stream insect for toxicity testing under field and laboratory conditions because
      of its short life cycle, parthenogenetic mode of reproduction, and it represents
      a group considered sensitive to environmental stressors. In this study, a colony
      of C. triangulifer was reared using a defined diet of three diatoms, Mayamaea
      atomus var. permitis, Nitzschia cf. pusilla, and Achnanthidium minutissimum.
      Percent survival (?80%), fecundity measurements (?1000 eggs) and pre-egg laying
      weights were used as indicators of overall colony health and fitness in our
      laboratory water (Lab-line) and in Moderately Hard Reconstituted Water (MHRW).
      Lab-line reared C. triangulifer had average survival rate of 92.69% for eleven
      generations and 82.99% over thirteen generations. MHRW reared C. triangulifer had
      an average survival rate of 80.65% for four generations and three generations of
      fecundities greater than 1000 eggs per individual. Pre-egg laying weight and
      fecundity were highly correlated and a best-fit model equation was derived to
      estimate egg counts for future generations. Establishment of this culturing
      protocol provides a more ecologically relevant species for toxicity testing and
      aids in further stressor identification for stream bioassessments.

PMID- 24894452
TI  - Clinical results of primary malignant musculoskeletal tumor treated by wide
      resection and recycling autograft reconstruction using liquid nitrogen.
AB  - AIM: To evaluate the clinical results of primary malignant musculoskeletal tumors
      treated with wide resection and recycling autograft reconstruction using liquid
      nitrogen. METHODS: We reviewed 12 patients who had a primary malignant bone and
      soft tissue tumor treated by wide resection and recycling autograft
      reconstruction using liquid nitrogen between March 2006 and March 2013. The
      results were judged by recurrence, functional status and complications.
      Functional status was assessed according to the Musculoskeletal Tumor Society
      Score (MSTSS). Clinical failure was defined as need for reoperation in order to
      change the type of reconstruction or to amputate, and the presence of local
      recurrence. RESULTS: The most common tumor was osteosarcoma (eight cases)
      followed by Ewing's sarcoma (two cases). The tibia was the most frequently
      involved skeletal site (six cases) followed by the femur (three cases). The
      median follow-up period was 32 months. In 12 patients, 7 were still alive without
      recurrence. There were 3 clinical failures: 1 local recurrence and 2 graft
      complications at 28, 51 and 20 months after reconstruction, respectively. The
      main complication was infection (three cases). All osteotomy sites were
      radiographic unions, and the union time was 8.2 +/- 2.7 months. The mean +/- SD
      MSTSS score was 79% +/- 11%; excellent functional results were achieved in seven
      patients. CONCLUSIONS: Recycling autograft reconstruction using liquid nitrogen
      had favorable clinical outcomes in terms of functional status and local
      recurrence. This reconstruction method, therefore, represents a reasonable
      alternative for limb salvage surgery.

PMID- 24894453
TI  - Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome
      sequence analysis is dependent on asymmetric dimerization and sensitive to
      cetuximab.
AB  - BACKGROUND: Inhibition of the activated epidermal growth factor receptor (EGFR)
      with either enzymatic kinase inhibitors or anti-EGFR antibodies such as
      cetuximab, is an effective modality of treatment for multiple human cancers.
      Enzymatic EGFR inhibitors are effective for lung adenocarcinomas with somatic
      kinase domain EGFR mutations while, paradoxically, anti-EGFR antibodies are more
      effective in colon and head and neck cancers where EGFR mutations occur less
      frequently. In colorectal cancer, anti-EGFR antibodies are routinely used as
      second-line therapy of KRAS wild-type tumors. However, detailed mechanisms and
      genomic predictors for pharmacological response to these antibodies in colon
      cancer remain unclear. FINDINGS: We describe a case of colorectal adenocarcinoma,
      which was found to harbor a kinase domain mutation, G724S, in EGFR through whole
      genome sequencing. We show that G724S mutant EGFR is oncogenic and that it
      differs from classic lung cancer derived EGFR mutants in that it is cetuximab
      responsive in vitro, yet relatively insensitive to small molecule kinase
      inhibitors. Through biochemical and cellular pharmacologic studies, we have
      determined that cells harboring the colon cancer-derived G719S and G724S mutants
      are responsive to cetuximab therapy in vitro and found that the requirement for
      asymmetric dimerization of these mutant EGFR to promote cellular transformation
      may explain their greater inhibition by cetuximab than small-molecule kinase
      inhibitors. CONCLUSION: The colon-cancer derived G719S and G724S mutants are
      oncogenic and sensitive in vitro to cetuximab. These data suggest that patients
      with these mutations may benefit from the use of anti-EGFR antibodies as part of
      the first-line therapy.

PMID- 24894454
TI  - The role of accessibility policies and other determinants of health care
      provision in the initial prognosis of malignant melanoma: a cross-sectional
      study.
AB  - BACKGROUND: The prognostic benefit of health care service provision and delivery
      policies for patients with malignant melanoma (MM) is not yet clear. OBJECTIVE:
      To analyze the role of health care provision determinants in the initial
      prognosis of MM. METHODS: A multicenter cross-sectional study was conducted at 14
      public hospitals and recruited 3550 patients with MM between 2000 and 2009. The
      study variables were analyzed using univariate and multivariate models to
      identify their role in the variations observed. RESULTS: In a 10-year period, the
      number of patients with MM increased by 78.54%, with primary in situ MM (Tis) or
      MMs with a Breslow thickness <1 mm (T1) representing 51.72% of the total number
      of MMs in 2000, increasing to 62.23% by the end of the study period (P = .005).
      Among the variables that explained the variation in MM frequency the year of
      diagnosis after 2004 (univariate odds ratio [OR], 1.43 [P < .001]; multivariate
      OR, 1.36 [P = .005]) and diagnosis in centers with specific fast-track referral
      systems (univariate OR, 1.24 [P = .01]; multivariate OR, 1.59 [P = .025]) were
      shown to explain the increasing frequency of Tis-T1 MM. LIMITATIONS: The primary
      potential limitation of this study is its retrospective nature. CONCLUSION:
      Health care provision policies and interventions aimed at improving accessibility
      to specialized care appear to explain the increasing frequency of Tis-T1 MM.

PMID- 24894456
TI  - Infantile myofibromatosis: a series of 28 cases.
AB  - BACKGROUND: Infantile myofibromatosis (IM) is a rare disorder of
      fibroblastic/myofibroblastic proliferation in children. OBJECTIVES: We sought to
      document common and unusual characteristics of patients with IM. METHODS: This
      was a retrospective study of 28 children diagnosed with histopathologically
      confirmed IM between 1992 and 2012. Epidemiologic, clinical, and treatment data
      were reviewed. RESULTS: IM was more frequent in boys (60.8%). Skin lesions were
      congenital in 64.3% of cases. The solitary form accounted for 50% of cases. Most
      nodules were painless, arising in cutaneous or subcutaneous tissue. The
      multicentric form accounted for 39% of cases; the skin, subcutaneous tissue, or
      muscle was involved in 97.8% of cases, and the bones in 50% of cases. The
      generalized form had a mortality rate of 33% (one-third of cases). Multicentric
      and generalized forms regressed spontaneously; severe local complications were
      observed, and late recurrent nodules developed in a few cases. LIMITATIONS: The
      retrospective review and the ascertainment of patients (from the departments of
      obstetrics and pediatrics) may have introduced bias in the analysis of severity
      of the different forms of IM. CONCLUSION: The diagnosis of IM must be confirmed
      histopathologically because the clinical presentation can be misleading. The
      prognosis is usually good, although local morbidity can occur. The generalized
      and multicentric forms merit long-term follow-up.

PMID- 24894455
TI  - Palmoplantar psoriasis is associated with greater impairment of health-related
      quality of life compared with moderate to severe plaque psoriasis.
AB  - BACKGROUND: The impact of palmoplantar psoriasis on health-related quality of
      life (QoL) is largely unknown. OBJECTIVE: We sought to compare clinical
      characteristics and patient-reported outcomes between patients with palmoplantar
      psoriasis and moderate to severe plaque psoriasis. METHODS: We conducted a cross
      sectional study of patients with plaque psoriasis (N=1153) and palmoplantar
      psoriasis (N=66) currently receiving systemic or light treatment for psoriasis.
      RESULTS: Patients with palmoplantar psoriasis were more likely to report
      Dermatology Life Quality Index scores that correspond to at least a moderate
      impact on QoL (odds ratio [OR] 2.08; 95% confidence interval [CI] 1.20-3.61);
      problems with mobility (OR 1.98; 95% CI 1.10-3.58), self-care (OR 3.12; 95% CI
      1.24-7.86), and usual activities (OR 2.47; 95% CI 1.44-4.22) on the European
      Quality of Life-5 Dimensions questionnaire; and heavy topical prescription use of
      at least twice daily in the preceding week (OR 2.81; 95% CI 1.63-4.85) than those
      with plaque psoriasis. LIMITATIONS: Our assessment tools may not account for all
      dimensions of health-related QoL affected by palmoplantar disease, and these
      results may not be generalizable to patients with milder forms of psoriasis.
      CONCLUSION: Patients with palmoplantar psoriasis experience greater health
      related QoL impairment and are more likely to report heavy use of topical
      prescriptions than those with moderate to severe plaque psoriasis.

PMID- 24894458
TI  - Detection and prevalence of drug use in arrested drivers using the Drager Drug
      Test 5000 and Affiniton DrugWipe oral fluid drug screening devices.
AB  - The use of oral fluid (OF) drug testing devices offers the ability to rapidly
      obtain a drug screening result at the time of a traffic stop. We describe an
      evaluation of two such devices, the Drager Drug Test 5000 and the Affiniton
      DrugWipe, to detect drug use in a cohort of drivers arrested from an
      investigation of drug impaired driving (n = 92). Overall, 41% of these drivers
      were ultimately confirmed positive by mass spectrometry for the presence of one
      or more drugs. The most frequently detected drugs were cannabinoids (30%),
      benzodiazepines (11%) and cocaine (10%). Thirty-nine percent of drivers with
      blood alcohol concentrations >0.08 g/100 mL were found to be drug positive. Field
      test results obtained from OF samples were compared with collected OF and urine
      samples subsequently analyzed in the laboratory by gas or liquid chromatography
      mass spectrometry. The Drager Drug Test 5000 (DDT5000) and DrugWipe returned
      overall sensitivities of 51 and 53%, and positive predictive values of 93 and
      63%, respectively. The most notable difference in performance was the DDT5000's
      better sensitivity in detecting marijuana use. Both devices failed to detect
      benzodiazepine use. Oral fluid proved to be a more effective confirmatory
      specimen, with more drugs being confirmed in OF than urine. 

PMID- 24894459
TI  - Screening Madness in American Culture.
AB  - This two-step argument first establishes that the majority of recent American
      films dealing with mental illness draw on a traditional iconography of madness as
      it has been established over the centuries in Western culture. In this vocabulary
      of images, the mad are typically seen as wise fools, as dangerous villains or as
      gifted geniuses. The author then argues that some of these new films add a fourth
      category in which the mad are defined as normal and the person with autism as the
      embodiment of this normalcy. A close examination of the films then suggests that
      high functioning autism has become the embodiment of America's current cultural
      condition. 

PMID- 24894457
TI  - Bioinformatic and proteomic analysis of bulk histones reveals PTM crosstalk and
      chromatin features.
AB  - Systems analysis of chromatin has been constrained by complex patterns and
      dynamics of histone post-translational modifications (PTMs), which represent
      major challenges for both mass spectrometry (MS) and immuno-based approaches
      (e.g., chromatin immuno-precipitation, ChIP). Here we present a proof-of-concept
      study demonstrating that crosstalk among PTMs and their functional significance
      can be revealed via systematic bioinformatic and proteomic analysis of steady
      state histone PTM levels from cells under various perturbations. Using high
      resolution tandem MS, we quantified 53 modification states from all core histones
      and their conserved variants in the unicellular eukaryotic model organism
      Tetrahymena. By correlating histone PTM patterns across 15 different conditions,
      including various physiological states and mutations of key histone modifying
      enzymes, we identified 5 specific chromatin states with characteristic covarying
      histone PTMs and associated them with distinctive functions in replication,
      transcription, and DNA repair. In addition to providing a detailed picture on
      histone PTM crosstalk at global levels, this work has established a novel
      bioinformatic and proteomic approach, which can be adapted to other organisms and
      readily scaled up to allow increased resolution of chromatin states. 

PMID- 24894461
TI  - Physicians' perceptions regarding the detection and management of malnutrition in
      Canadian hospitals: results of a Canadian Malnutrition Task Force survey.
AB  - OBJECTIVES: Since malnutrition is common in Canadian hospitals, physicians
      frequently encounter patients with significantly impaired nutrition status. The
      objective of this study was to determine physician attitudes and perceptions
      regarding the detection and management of malnutrition in Canadian hospitals.
      MATERIALS AND METHODS: A survey based on a previously developed questionnaire
      that focused on guidelines for nutrition support of hospitalized patients was
      completed by Canadian physicians working on wards in the 18 hospitals
      participating in the Canadian Malnutrition Task Force study. Data were analyzed
      descriptively and according to ward (medical vs surgical) and hospital type
      (academic vs community). RESULTS: The survey was completed by 428 of the 1220
      physicians who were provided with a questionnaire and asked to participate
      (response rate 35%). While physicians believe that nutrition assessment should be
      performed at admission (364/419 [87%]), during hospitalization (363/421 [86%]),
      and at discharge (327/418 [78%]), most felt that this was not being done on a
      regular basis (admission, 140/423 [33%]; during hospitalization, 175/423 [41%];
      at discharge, 121/424 [29%]). Similarly there was a gap between what was
      perceived to be the ideal management of hospital-related malnutrition and current
      practices. Physicians felt that the team's nutrition education and use of
      dietetic resources could be increased, and although their nutrition knowledge was
      limited, they felt that hospital-associated malnutrition was very relevant to the
      care they provided. CONCLUSIONS: A multidisciplinary team is needed to address
      hospital malnutrition, and educational strategies that target physicians are
      needed to promote better detection and management throughout the hospital stay.

PMID- 24894462
TI  - Refractory pyoderma gangrenosum in an infant.
AB  - We present a rare case of infantile pyoderma gangrenosum with an extended course
      and limited response to treatment. Despite extensive examination for an
      underlying disorder, the case remains idiopathic. 

PMID- 24894460
TI  - Errorless learning of prospective memory tasks: An experimental investigation in
      people with memory disorders.
AB  - The term prospective memory (PM) refers to memory for future intentions. PM
      problems are frequent in people with cognitive impairment and, because they are
      central to the realisation of many everyday goals, are important in
      rehabilitation. Event-based PM tasks (EBPM) are environmentally-cued and have
      primarily mnemonic demands, whereas time-based PM tasks (TBPM) require self
      initiated retrieval, and have greater executive demands. Errorless learning (EL)
      is an encoding method that results in superior retrospective memory compared with
      "errorful" learning (EF). As this EL advantage (ELA) likely stems from its
      reduced explicit memory demands, and there is no such advantage for executive
      tasks, a greater ELA for EBPM than TBPM was predicted. Fourteen adults with
      neurological memory impairment completed PM tasks under four counterbalanced
      conditions: EL of EBPM, EL of TBPM, EF of EBPM, and EF of TBPM. A significant ELA
      was observed for EBPM (d = .63), but not TBPM (d = -.01). These results extend
      the evidence for EL within cognitive rehabilitation, by showing for the first
      time that the method can benefit future action in addition to retrospective
      memory. The clinical implications are also clear: errorless learning techniques
      may be usefully employed to support completion of day-to-day EBPM tasks. 

PMID- 24894463
TI  - Symmetric exchange of multi-protein building blocks between stationary focal
      adhesions and the cytosol.
AB  - How can the integrin adhesome get self-assembled locally, rapidly, and correctly
      as diverse cell-matrix adhesion sites? Here, we investigate this question by
      exploring the cytosolic state of integrin-adhesome components and their dynamic
      exchange between adhesion sites and cytosol. Using fluorescence cross-correlation
      spectroscopy (FCCS) and fluorescence recovery after photobleaching (FRAP) we
      found that the integrin adhesome is extensively pre-assembled already in the
      cytosol as multi-protein building blocks for adhesion sites. Stationary focal
      adhesions release symmetrically the same types of protein complexes that they
      recruit, thereby keeping the cytosolic pool of building blocks spatiotemporally
      uniform. We conclude a model in which multi-protein building blocks enable rapid
      and modular self-assembly of adhesion sites and symmetric exchange of these
      building blocks preserves their specifications and thus the assembly logic of the
      system.DOI: http://dx.doi.org/10.7554/eLife.02257.001. 

PMID- 24894464
TI  - Complete morphologies of basal forebrain cholinergic neurons in the mouse.
AB  - The basal forebrain cholinergic system modulates neuronal excitability and
      vascular tone throughout the cerebral cortex and hippocampus. This system is
      severely affected in Alzheimer's disease (AD), and drug treatment to enhance
      cholinergic signaling is widely used as symptomatic therapy in AD. Defining the
      full morphologies of individual basal forebrain cholinergic neurons has, until
      now, been technically beyond reach due to their large axon arbor sizes. Using
      genetically-directed sparse labeling, we have characterized the complete
      morphologies of basal forebrain cholinergic neurons in the mouse. Individual
      arbors were observed to span multiple cortical columns, and to have >1000 branch
      points and total axon lengths up to 50 cm. In an AD model, cholinergic axons were
      slowly lost and there was an accumulation of axon-derived material in discrete
      puncta. Calculations based on published morphometric data indicate that basal
      forebrain cholinergic neurons in humans have a mean axon length of ~100
      meters.DOI: http://dx.doi.org/10.7554/eLife.02444.001. 

PMID- 24894466
TI  - Do trypanosome turncoats wait before they commit?
AB  - The strategy that sleeping sickness parasites use to evade the mammalian immune
      system may be linked to the metamorphosis that allows them to transfer from
      mammals into tsetse flies. 

PMID- 24894467
TI  - How do we walk and chew gum at the same time?
AB  - A genetic approach has been used to map the neural circuits that control and
      coordinate the tongue and jaw muscles. 

PMID- 24894465
TI  - Sex-specific processing of social cues in the medial amygdala.
AB  - Animal-animal recognition within, and across species, is essential for predator
      avoidance and social interactions. Despite its essential role in orchestrating
      responses to animal cues, basic principles of information processing by the
      vomeronasal system are still unknown. The medial amygdala (MeA) occupies a
      central position in the vomeronasal pathway, upstream of hypothalamic centers
      dedicated to defensive and social responses. We have characterized sensory
      responses in the mouse MeA and uncovered emergent properties that shed new light
      onto the transformation of vomeronasal information into sex- and species-specific
      responses. In particular, we show that the MeA displays a degree of stimulus
      selectivity and a striking sexually dimorphic sensory representation that are not
      observed in the upstream relay of the accessory olfactory bulb (AOB).
      Furthermore, our results demonstrate that the development of sexually dimorphic
      circuits in the MeA requires steroid signaling near the time of puberty to
      organize the functional representation of sensory stimuli.DOI:
      http://dx.doi.org/10.7554/eLife.02743.001. 

PMID- 24894470
TI  - Eyes on the prize.

PMID- 24894468
TI  - Correction: Rheotaxis facilitates upstream navigation of mammalian sperm cells.

PMID- 24894473
TI  - Is novelty overrated?

PMID- 24894471
TI  - Complexity of molecular crowding in cell-free enzymatic reaction networks.

PMID- 24894472
TI  - Reply to 'Complexity of molecular crowding in cell-free enzymatic reaction
      networks'.

PMID- 24894475
TI  - Cluster catalysis: a subtle form of recognition.

PMID- 24894476
TI  - 2D materials: Metallic when narrow.

PMID- 24894477
TI  - Levitating nanoparticles: Non-equilibrium nano-thermometry.

PMID- 24894478
TI  - Transition-metal oxides: It takes two to waver.

PMID- 24894480
TI  - Big lessons about small things.

PMID- 24894481
TI  - Cognitive impact of cytotoxic agents in mice.
AB  - RATIONALE AND OBJECTIVES: Adjuvant chemotherapy is associated with changes in
      cognition in a subgroup of cancer patients. Chemotherapy is generally given as a
      combination of cytotoxic agents, which makes it hard to define the agent
      responsible for these observed changes. Literature on animal experiments has been
      difficult to interpret due to variance in experimental setup. METHODS: We
      examined the effects of cytotoxic agents administered separately on various
      cognitive measures in a standardized animal model. Male C57Bl/6 mice received
      cyclophosphamide, docetaxel, doxorubicin, 5-fluorouracil, methotrexate, or
      topotecan. These agents represent different compound classes based on their
      working mechanism and are frequently prescribed in the clinic. A control group
      received saline. Behavioral testing started 2 or 15 weeks after treatment and
      included testing general measures of behavior and cognitive task performance:
      spontaneous behavior in an automated home cage, open field, novel location
      recognition (NLR), novel object recognition (NOR), Barnes maze, contextual fear
      conditioning, and a simple choice reaction time task (SCRTT). RESULTS:
      Cyclophosphamide, docetaxel, and doxorubicin administration affected spontaneous
      activity in the automated home cage. All cytotoxic agents affected memory (NLR
      and/or NOR). Spatial memory measured in the Barnes maze was affected after
      administration with doxorubicin, 5-fluorouracil, and topotecan. Decreased
      inhibition in the SCRTT was observed after treatment with cyclophosphamide,
      docetaxel, and topotecan. CONCLUSIONS: Our data show that, in mice, a single
      treatment with a cytotoxic agent causes cognitive impairment. Not all cytotoxic
      agents affected the same cognitive domains, which might be explained by
      differences in working mechanisms of the various agents.

PMID- 24894483
TI  - Heritability of cardiac vagal control in 24-h heart rate variability recordings:
      influence of ceiling effects at low heart rates.
AB  - This study estimated the heritability of 24-h heart rate variability (HRV)
      measures, while considering ceiling effects on HRV at low heart rates during the
      night. HRV was indexed by the standard deviation of all valid interbeat intervals
      (SDNN), the root mean square of differences between valid, successive interbeat
      intervals (RMSSD), and peak-valley respiratory sinus arrhythmia (pvRSA). Sleep
      and waking levels of cardiac vagal control were assessed in 1,003 twins and 285
      of their non-twin siblings. Comparable heritability estimates were found for SDNN
      (46%-53%), RMSSD (49%-54%), and pvRSA (48%-57%) during the day and night. A
      nighttime ceiling effect was revealed in 10.7% of participants by a quadratic
      relationship between mean pvRSA and the interbeat interval. Excluding these
      participants did not change the heritability estimates. The genetic factors
      influencing ambulatory pvRSA, RMSSD, and SDNN largely overlap. These results
      suggest that gene-finding studies may pool the different cardiac vagal indices
      and that exclusion of participants with low heart rates is not required.

PMID- 24894482
TI  - Increased 5-hydroxymethylcytosine and decreased 5-methylcytosine are indicators
      of global epigenetic dysregulation in diffuse intrinsic pontine glioma.
AB  - INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a malignant pediatric
      brain tumor associated with dismal outcome. Recent high-throughput molecular
      studies have shown a high frequency of mutations in histone-encoding genes (H3F3A
      and HIST1B) and distinctive epigenetic alterations in these tumors. Epigenetic
      alterations described in DIPG include global DNA hypomethylation. In addition to
      the generally repressive methylcytosine DNA alteration, 5-hydroxymethylation of
      cytosine (5hmC) is recognized as an epigenetic mark associated with active
      chromatin. We hypothesized that in addition to alterations in DNA methylation,
      that there would be changes in 5hmC. To test this hypothesis, we performed
      immunohistochemical studies to compare epigenetic alterations in DIPG to
      extrapontine adult and pediatric glioblastoma (GBM) and normal brain. A total of
      124 tumors were scored for histone 3 lysine 27 trimethylation (H3K27me3) and
      histone 3 lysine 9 trimethylation (H3K9me3) and 104 for 5hmC and 5-methylcytosine
      (5mC). An H-score was derived by multiplying intensity (0-2) by percentage of
      positive tumor nuclei (0-100%). RESULTS: We identified decreased H3K27me3 in the
      DIPG cohort compared to pediatric GBM (p < 0.01), adult GBM (p < 0.0001) and
      normal brain (p < 0.0001). H3K9me3 was not significantly different between tumor
      types. Global DNA methylation as measured by 5mC levels were significantly lower
      in DIPG compared to pediatric GBM (p < 0.001), adult GBM (p < 0.01), and normal
      brain (p < 0.01). Conversely, 5hmC levels were significantly higher in DIPG
      compared to pediatric GBM (p < 0.0001) and adult GBM (p < 0.0001). Additionally,
      in an independent set of DIPG tumor samples, TET1 and TET3 mRNAs were found to be
      overexpressed relative to matched normal brain. CONCLUSIONS: Our findings extend
      the immunohistochemical study of epigenetic alterations in archival tissue to
      DIPG specimens. Low H3K27me3, decreased 5mC and increased 5hmC are characteristic
      of DIPG in comparison with extrapontine GBM. In DIPG, the relative imbalance of
      5mC compared to 5hmC may represent an opportunity for therapeutic intervention.

PMID- 24894484
TI  - Lorna Arnold.

PMID- 24894485
TI  - The free and cued selective reminding test: Validation for mild cognitive
      impairment and Alzheimer's disease.
AB  - The International Working Group on Alzheimer's disease (AD) suggested the free
      and cued selective reminding test (FCSRT) to assess memory, as it showed high
      sensitivity and specificity in the differentiation of AD from healthy controls
      and other dementias. The FCSRT involves the use of selective reminding with
      semantic cueing in memory assessment. This study aims to validate the FCSRT for
      mild cognitive impairment (MCI) and AD through the analysis of the diagnostic
      accuracy and the suggestion of cut-off scores. Patients were classified into two
      groups according to standard criteria: MCI (n = 100) and AD (n = 70). A matched
      control group (n = 101) of cognitively healthy subjects was included. The
      reliability and the validity of the FCSRT were analysed on the immediate (IR) and
      delayed (DR) recalls. The Cronbach's alpha was 0.915 for the IR and 0.879 for the
      DR. The total recall measures revealed good areas under the curve for MCI (IR:
      .818; DR: .828) and excellent for AD (IR: .987; DR: .991). Furthermore, the MCI
      group was subdivided with respect to a non-similar/similar AD pattern of
      impairment, with almost half of the subjects showing an AD-like decline. This
      analysis represents a novel contribution regarding the properties of the FCSRT in
      illustrating the heterogeneity of MCI at baseline. The FCSRT has proved to be a
      very useful tool in the characterization of the memory impairment of the AD
      spectrum. 

PMID- 24894486
TI  - An unusual case of Acanthamoeba Polyphaga and Pseudomonas Aeruginosa keratitis.
AB  - A 56-year-old woman with a history of disposable soft contact lens wear was
      referred to our university eye center for a corneal ulcer. Based on the microbial
      culture, the initial diagnosis was bacterial keratitis, which was unresponsive to
      topical fortified antibiotics. The patient was then examined using in vivo
      confocal microscopy, which revealed Acanthamoeba infection. This case emphasizes
      the need to suspect Acanthamoeba infection in soft contact lens wearers who
      present with progressive ulcerative keratitis or progressively worsening corneal
      ulcers that are not responsive to the usual antimicrobial therapy. It is also
      important to consider the possibility of a coinfection with bacterial and
      Acanthamoeba species. VIRTUAL SLIDES: The virtual slide(s) for this article can
      be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5168343391150859.

PMID- 24894487
TI  - Peritoneal transport rate, systemic inflammation, and residual renal function
      determine peritoneal protein clearance in continuous ambulatory peritoneal
      dialysis patients.
AB  - BACKGROUND: Peritoneal protein clearance (Pcl) is related to the mortality of
      patients on continuous ambulatory peritoneal dialysis (CAPD) as well as technique
      failure. In this prospective observational study, we aimed to investigate factors
      associated with the level of Pcl. METHODS: We prospectively enrolled 344
      prevalent CAPD patients. A standard peritoneal equilibrium test was conducted for
      each patient. Baseline demographics, biochemistry, and Pcl were recorded.
      RESULTS: The average Pcl of the patients was 97.40 +/- 54.14 mL/day. Peritoneal
      transport level, serum high-sensitivity C-reactive protein (hsCRP), and residual
      glomerular filtration rate (rGFR) were independently related to Pcl. The standard
      beta values were 0.53, 0.17, and -0.10, respectively. Moreover, compared with non
      diabetic patients, diabetic patients had a non-significantly higher level of Pcl
      (104.90 +/- 48.65 vs. 96.15 +/- 54.97 mL/day; P = 0.06). CONCLUSION: Continuous
      ambulatory peritoneal dialysis patients lose a high amount of protein through the
      peritoneum each day. The Pcl value is positively related to the level of
      peritoneal transport and hsCRP and negatively related to the rGFR.

PMID- 24894489
TI  - Ex vivo culture of mouse embryonic skin and live-imaging of melanoblast
      migration.
AB  - Melanoblasts are the neural crest derived precursors of melanocytes; the cells
      responsible for producing the pigment in skin and hair. Melanoblasts migrate
      through the epidermis of the embryo where they subsequently colonize the
      developing hair follicles(1,2). Neural crest cell migration is extensively
      studied in vitro but in vivo methods are still not well developed, especially in
      mammalian systems. One alternative is to use ex vivo organotypic culture(3-6).
      Culture of mouse embryonic skin requires the maintenance of an air-liquid
      interface (ALI) across the surface of the tissue(3,6). High resolution live
      imaging of mouse embryonic skin has been hampered by the lack of a good method
      that not only maintains this ALI but also allows the culture to be inverted and
      therefore compatible with short working distance objective lenses and most
      confocal microscopes. This article describes recent improvements to a method that
      uses a gas permeable membrane to overcome these problems and allow high
      resolution confocal imaging of embryonic skin in ex vivo culture(6). By using a
      melanoblast specific Cre-recombinase expressing mouse line combined with the
      R26YFPR reporter line we are able to fluorescently label the melanoblast
      population within these skin cultures. The technique allows live-imaging of
      melanoblasts and observation of their behavior and interactions with the tissue
      in which they develop. Representative results are included to demonstrate the
      capability to live-image 6 cultures in parallel.

PMID- 24894488
TI  - Hes-1 SUMOylation by protein inhibitor of activated STAT1 enhances the
      suppressing effect of Hes-1 on GADD45alpha expression to increase cell survival.
AB  - BACKGROUND: Hairy and Enhancer of split 1 (Hes-1) is a transcriptional repressor
      that plays an important role in neuronal differentiation and development, but
      post-translational modifications of Hes-1 are much less known. In the present
      study, we aimed to investigate whether Hes-1 could be SUMO-modified and identify
      the candidate SUMO acceptors on Hes-1. We also wished to examine the role of the
      SUMO E3 ligase protein inhibitor of activated STAT1 (PIAS1) in SUMOylation of Hes
      1 and the molecular mechanism of Hes-1 SUMOylation. Further, we aimed to identify
      the molecular target of Hes-1 and examine how Hes-1 SUMOylation affects its
      molecular target to affect cell survival. RESULTS: In this study, by using
      HEK293T cells, we have found that Hes-1 could be SUMO-modified and Hes-1
      SUMOylation was greatly enhanced by the SUMO E3 ligase PIAS1 at Lys8, Lys27 and
      Lys39. Furthermore, Hes-1 SUMOylation stabilized the Hes-1 protein and increased
      the transcriptional suppressing activity of Hes-1 on growth arrest and DNA damage
      inducible protein alpha (GADD45alpha) expression. Overexpression of GADD45alpha
      increased, whereas knockdown of GADD45alphaalpha expression decreased cell
      apoptosis. In addition, H2O2 treatment increased the association between PIAS1
      and Hes-1 and enhanced the SUMOylation of Hes-1 for endogenous protection.
      Overexpression of Hes-1 decreased H2O2-induced cell death, but this effect was
      blocked by transfection of the Hes-1 triple sumo-mutant (Hes-1 3KR).
      Overexpression of PIAS1 further facilitated the anti-apoptotic effect of Hes-1.
      Moreover, Hes-1 SUMOylation was independent of Hes-1 phosphorylation and vice
      versa. CONCLUSIONS: The present results revealed, for the first time, that Hes-1
      could be SUMO-modified by PIAS1 and GADD45alpha is a novel target of Hes-1.
      Further, Hes-1 SUMOylation mediates cell survival through enhanced suppression of
      GADD45alpha expression. These results revealed a novel role of Hes-1 in addition
      to its involvement in Notch signaling. They also implicate that SUMOylation could
      be an important posttranslational modification that regulates cell survival.

PMID- 24894491
TI  - The role of international travel in the spread of methicillin-resistant
      Staphylococcus aureus.
AB  - BACKGROUND: Increasing international travel has facilitated the transmission of
      various multidrug-resistant bacteria-including methicillin-resistant
      Staphylococcus aureus (MRSA)-across continents. Individuals may acquire MRSA from
      the community, healthcare facilities, or even from animal exposure. Skin contact
      with colonized individuals, fomites, or animals during an overseas trip may
      result in either asymptomatic colonization or subsequent clinically significant
      MRSA disease. MRSA strains that harbor the Panton-Valentine leucocidin toxin are
      particularly associated with community transmission and may potentially have
      enhanced virulence resulting in serious skin and soft tissue infections or even
      necrotizing pneumonia. More importantly, secondary transmission events upon
      return from traveling have been documented, leading to potentially detrimental
      outbreaks within the community or the healthcare setting. We sought to review the
      existing literature relating to the role of various aspects of travel in the
      spread of MRSA. Risk factors for acquiring MRSA during travel together with the
      need for targeted screening of high-risk individuals will also be explored.
      METHODS: Data for this article were identified via PubMed searches using a
      combination of search terms: "methicillin resistance," "MRSA," "livestock
      associated MRSA," "community-associated MRSA," "travel," and "outbreak." The
      relevant articles were extensively perused to determine secondary sources of
      data. RESULTS AND CONCLUSIONS: Our review of the current literature suggests that
      international travel plays a significant role in the transmission of MRSA,
      potentially contributing to the replacement of existing endemic MRSA with fitter
      and more transmissible strains. Therefore, selective and targeted screening of
      travelers with risk factors for MRSA colonization may be beneficial. Healthcare
      professionals and patients should be considered for screening if they were to
      return from endemic areas, with the former group decolonized before returning to
      patient care work, in order to reduce the transmission of MRSA to vulnerable
      patient populations.

PMID- 24894492
TI  - The use of health status questionnaires in the management of chronic obstructive
      pulmonary disease patients in clinical practice.
AB  - Current guidelines recommend chronic obstructive pulmonary disease (COPD)
      management based on symptoms or health status assessment and lung function
      parameters. However, COPD is a complex and heterogeneous disease that needs an
      individualized approach for proper disease management. A structured consultation
      including health status assessment tools, such as the Clinical COPD Questionnaire
      and the COPD Assessment Test should improve the quality of the consultation,
      providing more information than symptoms alone. Both questionnaires are designed
      to provide the clinician information enabling a more personalized disease
      approach and subsequent management. Although both Clinical COPD Questionnaire and
      COPD Assessment Test have good discriminate properties, their use as prognostic
      markers of severity and their ability to modify disease management has not yet
      been fully established. New studies are needed to further determine their value
      on several disease outcomes. 

PMID- 24894490
TI  - Overlap of expression quantitative trait loci (eQTL) in human brain and blood.
AB  - BACKGROUND: Expression quantitative trait loci (eQTL) are genomic regions
      regulating RNA transcript expression levels. Genome-wide Association Studies
      (GWAS) have identified many variants, often in non-coding regions, with unknown
      functions and eQTL provide a possible mechanism by which these variants may
      influence observable phenotypes. Limited access and availability of tissues such
      as brain has led to the use of blood as a substitute for eQTL analyses. METHODS:
      Here, we evaluate the overlap of eQTL reported in published studies conducted in
      blood and brain tissues to assess the utility of blood as an alternative to brain
      tissue in the study of neurological and psychiatric conditions. Expression QTL
      results from eight published brain studies were compared to blood eQTL identified
      in from a meta-analysis involving 5,311 individuals. We accounted for differences
      in SNP platforms and study design by using SNP proxies in high linkage
      disequilibrium with reported eQTL. The degree of overlap between studies was
      calculated by ascertaining if an eQTL identified in one study was also identified
      in the other study. RESULTS: The percentage of eQTL overlapping for brain and
      blood expression after adjusting for differences in sample size ranged from 13 -
      23% (mean 19.2%). Amongst pairs of brain studies eQTL overlap ranged from 0 -
      35%, with higher degrees of overlap found for studies using expression data
      collected from the same brain region. CONCLUSION: Our results suggest that
      whenever possible tissue specific to the pathophysiology of the disease being
      studied should be used for transcription analysis.

PMID- 24894493
TI  - Malignant rhabdoid tumor of the liver presented with initial tumor rupture.
AB  - Malignant rhabdoid tumor (MRT) of the liver is a rare, highly aggressive tumor of
      early childhood. We report a 6-month-old boy who was diagnosed with MRT of the
      liver and presented with spontaneous tumor rupture. The patient underwent
      intensified chemotherapy and a radical surgical procedure. Twenty four months
      from the time of the diagnosis, he is alive without evidence of disease. This is
      the second report of prolonged survival after initial rupture of hepatic MRT. 

PMID- 24894494
TI  - A technique to screen American beech for resistance to the beech scale insect
      (Cryptococcus fagisuga Lind.).
AB  - Beech bark disease (BBD) results in high levels of initial mortality, leaving
      behind survivor trees that are greatly weakened and deformed. The disease is
      initiated by feeding activities of the invasive beech scale insect, Cryptococcus
      fagisuga, which creates entry points for infection by one of the Neonectria
      species of fungus. Without scale infestation, there is little opportunity for
      fungal infection. Using scale eggs to artificially infest healthy trees in
      heavily BBD impacted stands demonstrated that these trees were resistant to the
      scale insect portion of the disease complex(1). Here we present a protocol that
      we have developed, based on the artificial infestation technique by Houston(2),
      which can be used to screen for scale-resistant trees in the field and in smaller
      potted seedlings and grafts. The identification of scale-resistant trees is an
      important component of management of BBD through tree improvement programs and
      silvicultural manipulation.

PMID- 24894495
TI  - Plant host and soil origin influence fungal and bacterial assemblages in the
      roots of woody plants.
AB  - Microbial communities in plant roots provide critical links between above- and
      belowground processes in terrestrial ecosystems. Variation in root communities
      has been attributed to plant host effects and microbial host preferences, as well
      as to factors pertaining to soil conditions, microbial biogeography and the
      presence of viable microbial propagules. To address hypotheses regarding the
      influence of plant host and soil biogeography on root fungal and bacterial
      communities, we designed a trap-plant bioassay experiment. Replicate Populus,
      Quercus and Pinus plants were grown in three soils originating from alternate
      field sites. Fungal and bacterial community profiles in the root of each
      replicate were assessed through multiplex 454 amplicon sequencing of four loci
      (i.e., 16S, SSU, ITS, LSU rDNA). Soil origin had a larger effect on fungal
      community composition than did host species, but the opposite was true for
      bacterial communities. Populus hosted the highest diversity of rhizospheric fungi
      and bacteria. Root communities on Quercus and Pinus were more similar to each
      other than to Populus. Overall, fungal root symbionts appear to be more
      constrained by dispersal and biogeography than by host availability.

PMID- 24894496
TI  - Harnessing the immunological properties of stem cells as a therapeutic option for
      diabetic nephropathy.
AB  - Diabetic nephropathy is the leading and possibly the most devastating
      complication of diabetes, with a prevalence ranging from 25 to 40 % in diabetic
      individuals, and as such represents an important challenge for public health
      worldwide. As a major cause of end-stage renal disease, diabetic nephropathy also
      accounts for a large proportion of deaths in diabetic individuals. To date,
      therapeutic options for overt diabetic nephropathy include medical interventions
      to reduce blood glucose levels and to control blood pressure and proteinuria.
      Recent evidence suggests a strong role for inflammation in the development and
      progression of diabetic nephropathy. Various immune cells, cytokines and
      chemokines have been implicated in the onset of diabetic nephropathy, while
      immune-related transcription factors and adhesion molecules have been correlated
      with the establishment of a renal proinflammatory microenvironment. Both
      inflammation and immune activation may promote severe distress in the kidney,
      with subsequent increased local fibrosis, ultimately leading to the development
      of end-stage renal disease. Stem cells are undifferentiated cells capable of
      regenerating virtually any organ or tissue and bearing important immunoregulatory
      and anti-inflammatory properties. Due to the aforementioned considerations,
      significant interest has been ignited with regard to the use of stem cells as
      novel therapeutics for diabetic nephropathy. Here, we will be examining in detail
      how anti-inflammatory properties of different populations of stem cells may offer
      novel therapy for the treatment of diabetic nephropathy.

PMID- 24894497
TI  - Quality of prenatal care questionnaire: instrument development and testing.
AB  - BACKGROUND: Utilization indices exist to measure quantity of prenatal care, but
      currently there is no published instrument to assess quality of prenatal care.
      The purpose of this study was to develop and test a new instrument, the Quality
      of Prenatal Care Questionnaire (QPCQ). METHODS: Data for this instrument
      development study were collected in five Canadian cities. Items for the QPCQ were
      generated through interviews with 40 pregnant women and 40 health care providers
      and a review of prenatal care guidelines, followed by assessment of content
      validity and rating of importance of items. The preliminary 100-item QPCQ was
      administered to 422 postpartum women to conduct item reduction using exploratory
      factor analysis. The final 46-item version of the QPCQ was then administered to
      another 422 postpartum women to establish its construct validity, and internal
      consistency and test-retest reliability. RESULTS: Exploratory factor analysis
      reduced the QPCQ to 46 items, factored into 6 subscales, which subsequently were
      validated by confirmatory factor analysis. Construct validity was also
      demonstrated using a hypothesis testing approach; there was a significant
      positive association between women's ratings of the quality of prenatal care and
      their satisfaction with care (r = 0.81). Convergent validity was demonstrated by
      a significant positive correlation (r = 0.63) between the "Support and Respect"
      subscale of the QPCQ and the "Respectfulness/Emotional Support" subscale of the
      Prenatal Interpersonal Processes of Care instrument. The overall QPCQ had
      acceptable internal consistency reliability (Cronbach's alpha = 0.96), as did
      each of the subscales. The test-retest reliability result (Intra-class
      correlation coefficient = 0.88) indicated stability of the instrument on repeat
      administration approximately one week later. Temporal stability testing confirmed
      that women's ratings of their quality of prenatal care did not change as a result
      of giving birth or between the early postpartum period and 4 to 6 weeks
      postpartum. CONCLUSION: The QPCQ is a valid and reliable instrument that will be
      useful in future research as an outcome measure to compare quality of care across
      geographic regions, populations, and service delivery models, and to assess the
      relationship between quality of care and maternal and infant health outcomes.

PMID- 24894499
TI  - Isoflavone aglycone content and the thermal, functional, and structural
      properties of soy protein isolates prepared from hydrothermally treated soybeans.
AB  - Soybeans were hydrothermally treated at 2 different temperatures (40  degrees C
      and 60  degrees C) and for 4 different hydration times (4, 8, 12, and 16 h) to
      (i) increase the isoflavone aglycone content in a soy protein isolate and (ii)
      evaluate the changes in thermal, functional, and structural properties of a soy
      protein isolate as a function of hydrothermal treatment conditions. Our study is
      the first to evaluate aglycone content, extraction yield, beta-glucosidase
      activity, differential scanning calorimetry, protein digestibility, scanning
      electron microscopy, water absorption capacity (WAC), foaming capacity (FC), and
      foaming stability of soy protein isolates prepared from hydrothermally treated
      soybeans. For aglycone enhancement and the extraction yield maintenance of soy
      protein isolates, the condition of 40  degrees C for 12 h was the best soybean
      hydrothermal treatment. The structural rearrangement of proteins that occurred
      with the hydrothermal treatment most likely promoted the capacity of proteins to
      bind to aglycone. Moreover, the structure shape and size of soy protein isolates
      verified by scanning electron microscopy appears to be related to the formation
      of hydrophobic surfaces and hydrophobic zones at 40  degrees C and 60  degrees C,
      respectively, affecting the protein digestibility, WAC, and FC of soy protein
      isolates. PRACTICAL APPLICATION: The aglycone content in the soy protein isolate
      can be improved with the hydrothermal treatment of soybeans. The temperature and
      time used for hydrothermal treatment must be selected in order to achieve a soy
      protein isolate with high aglycone content, extraction yield, and functionality.
      This technology is suitable for providing healthier soy protein isolates for food
      industry with improved functional and structural properties.

PMID- 24894498
TI  - Mck2-dependent infection of alveolar macrophages promotes replication of MCMV in
      nodular inflammatory foci of the neonatal lung.
AB  - Infection with cytomegalovirus (CMV) shows a worldwide high prevalence with only
      immunocompromised individuals or newborns to become symptomatic. The host's
      constitution and the pathogen's virulence determine whether disease occurs after
      infection. Mouse CMV (MCMV) is an appreciated pathogen for in vivo investigation
      of host-pathogen interactions. It has recently been reported that a single base
      pair deletion can spontaneously occur in the open reading frame of MCMV-encoded
      chemokine 2 (MCK2), preventing the expression of the full-length gene product. To
      study the consequences of this mutation, we compared the Mck2-defective reporter
      virus MCMV-3D with the newly generated repaired Mck2(+) mutant MCMV-3DR. Compared
      with MCMV-3D, neonatal mice infected with MCMV-3DR showed severe viral disease
      after lung infection. Viral disease coincided with high viral activity in
      multiple organs and increased virus replication in previously described nodular
      inflammatory foci (NIF) in the lung. Notably, MCMV-3DR showed tropism for
      alveolar macrophages in vitro and in vivo, whereas MCMV-3D did not infect this
      cell type. Moreover, in vivo depletion of alveolar macrophages reduced MCMV-3DR
      replication in the lung. We proposed an Mck2-mediated mechanism by which MCMV
      exploits alveolar macrophages to increase replication upon first encounter with
      the host's lung mucosa. 

PMID- 24894500
TI  - Tedna: a transposable element de novo assembler.
AB  - MOTIVATION: Recent technological advances are allowing many laboratories to
      sequence their research organisms. Available de novo assemblers leave repetitive
      portions of the genome poorly assembled. Some genomes contain high proportions of
      transposable elements, and transposable elements appear to be a major force
      behind diversity and adaptation. Few de novo assemblers for transposable elements
      exist, and most have either been designed for small genomes or 454 reads.
      RESULTS: In this article, we present a new transposable element de novo
      assembler, Tedna, which assembles a set of transposable elements directly from
      the reads. Tedna uses Illumina paired-end reads, the most widely used sequencing
      technology for de novo assembly, and forms full-length transposable elements.
      AVAILABILITY AND IMPLEMENTATION: Tedna is available at
      http://urgi.versailles.inra.fr/Tools/Tedna, under the GPLv3 license. It is
      written in C++11 and only requires the Sparsehash Package, freely available under
      the New BSD License. Tedna can be used on standard computers with limited RAM
      resources, although it may also use large memory for better results. Most of the
      code is parallelized and thus ready for large infrastructures.

PMID- 24894501
TI  - RAREMETAL: fast and powerful meta-analysis for rare variants.
AB  - SUMMARY: RAREMETAL is a computationally efficient tool for meta-analysis of rare
      variants genotyped using sequencing or arrays. RAREMETAL facilitates analyses of
      individual studies, accommodates a variety of input file formats, handles related
      and unrelated individuals, executes both single variant and burden tests and
      performs conditional association analyses. AVAILABILITY AND IMPLEMENTATION:
      http://genome.sph.umich.edu/wiki/RAREMETAL for executables, source code,
      documentation and tutorial.

PMID- 24894502
TI  - PePr: a peak-calling prioritization pipeline to identify consistent or
      differential peaks from replicated ChIP-Seq data.
AB  - MOTIVATION: ChIP-Seq is the standard method to identify genome-wide DNA-binding
      sites for transcription factors (TFs) and histone modifications. There is a
      growing need to analyze experiments with biological replicates, especially for
      epigenomic experiments where variation among biological samples can be
      substantial. However, tools that can perform group comparisons are currently
      lacking. RESULTS: We present a peak-calling prioritization pipeline (PePr) for
      identifying consistent or differential binding sites in ChIP-Seq experiments with
      biological replicates. PePr models read counts across the genome among biological
      samples with a negative binomial distribution and uses a local variance
      estimation method, ranking consistent or differential binding sites more
      favorably than sites with greater variability. We compared PePr with commonly
      used and recently proposed approaches on eight TF datasets and show that PePr
      uniquely identifies consistent regions with enriched read counts, high motif
      occurrence rate and known characteristics of TF binding based on visual
      inspection. For histone modification data with broadly enriched regions, PePr
      identified differential regions that are consistent within groups and
      outperformed other methods in scaling False Discovery Rate (FDR) analysis.
      AVAILABILITY AND IMPLEMENTATION: http://code.google.com/p/pepr-chip-seq/.

PMID- 24894503
TI  - Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series.
AB  - MOTIVATION: The widespread adoption of RNA-seq to quantitatively measure gene
      expression has increased the scope of sequencing experimental designs to include
      time-course experiments. maSigPro is an R package specifically suited for the
      analysis of time-course gene expression data, which was developed originally for
      microarrays and hence was limited in its application to count data. RESULTS: We
      have updated maSigPro to support RNA-seq time series analysis by introducing
      generalized linear models in the algorithm to support the modeling of count data
      while maintaining the traditional functionalities of the package. We show a good
      performance of the maSigPro-GLM method in several simulated time-course scenarios
      and in a real experimental dataset. AVAILABILITY AND IMPLEMENTATION: The package
      is freely available under the LGPL license from the Bioconductor Web site
      (http://bioconductor.org).

PMID- 24894504
TI  - Mirsynergy: detecting synergistic miRNA regulatory modules by overlapping
      neighbourhood expansion.
AB  - MOTIVATION: Identification of microRNA regulatory modules (MiRMs) will aid
      deciphering aberrant transcriptional regulatory network in cancer but is
      computationally challenging. Existing methods are stochastic or require a fixed
      number of regulatory modules. RESULTS: We propose Mirsynergy, an efficient
      deterministic overlapping clustering algorithm adapted from a recently developed
      framework. Mirsynergy operates in two stages: it first forms MiRMs based on co
      occurring microRNA (miRNA) targets and then expands each MiRM by greedily
      including (excluding) mRNAs into (from) the MiRM to maximize the synergy score,
      which is a function of miRNA-mRNA and gene-gene interactions. Using expression
      data for ovarian, breast and thyroid cancer from The Cancer Genome Atlas, we
      compared Mirsynergy with internal controls and existing methods. Mirsynergy-MiRMs
      exhibit significantly higher functional enrichment and more coherent miRNA-mRNA
      expression anti-correlation. Based on Kaplan-Meier survival analysis, we proposed
      several prognostically promising MiRMs and envisioned their utility in cancer
      research. AVAILABILITY AND IMPLEMENTATION: Mirsynergy is implemented/available as
      an R/Bioconductor package at www.cs.utoronto.ca/~yueli/Mirsynergy.html.

PMID- 24894505
TI  - SMaSH: a benchmarking toolkit for human genome variant calling.
AB  - MOTIVATION: Computational methods are essential to extract actionable information
      from raw sequencing data, and to thus fulfill the promise of next-generation
      sequencing technology. Unfortunately, computational tools developed to call
      variants from human sequencing data disagree on many of their predictions, and
      current methods to evaluate accuracy and computational performance are ad hoc and
      incomplete. Agreement on benchmarking variant calling methods would stimulate
      development of genomic processing tools and facilitate communication among
      researchers. RESULTS: We propose SMaSH, a benchmarking methodology for evaluating
      germline variant calling algorithms. We generate synthetic datasets, organize and
      interpret a wide range of existing benchmarking data for real genomes and propose
      a set of accuracy and computational performance metrics for evaluating variant
      calling methods on these benchmarking data. Moreover, we illustrate the utility
      of SMaSH to evaluate the performance of some leading single-nucleotide
      polymorphism, indel and structural variant calling algorithms. AVAILABILITY AND
      IMPLEMENTATION: We provide free and open access online to the SMaSH tool kit,
      along with detailed documentation, at smash.cs.berkeley.edu

PMID- 24894506
TI  - Differential Synaptic and Extrasynaptic Glutamate-Receptor Alterations in
      Striatal Medium-Sized Spiny Neurons of Aged YAC128 Huntington's Disease Mice.
AB  - Huntington's disease (HD) is a late-onset, slowly progressing neurodegenerative
      disorder caused by an expansion of glutamine repeats. The YAC128 mouse model has
      been widely used to study the progression of HD symptoms, but little is known
      about synaptic alterations in very old animals. The present experiments examined
      synaptic properties of striatal medium-sized spiny neurons (MSNs) in 16 month-old
      YAC128 mice. These mice were crossed with mice expressing enhanced green
      fluorescent protein (EGFP) under the control of either D1 or D2 dopamine receptor
      promoters to identify MSNs originating the direct and indirect pathways,
      respectively. The input-output curves of evoked excitatory postsynaptic currents
      mediated by activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors were reduced in MSNs in both
      pathways. In the presence of DL-threo-beta-Benzyloxyaspartic acid (DL-TBOA), a
      glutamate transporter blocker used to increase activation of extrasynaptic
      receptors, NMDA receptor-mediated currents displayed altered amplitudes, longer
      decay times, and greater charge (response areas) in both direct and indirect
      pathway MSNs in YAC128 mice compared to wildtype controls. Amplitudes were
      significantly increased, primarily in direct pathway MSNs while normalized areas
      were significantly increased only in indirect pathway MSNs, suggesting that the
      two types of MSNs are affected in different ways. It may be that indirect pathway
      neurons are more susceptible to changes in glutamate transport. Taken together,
      the present findings demonstrate differential alterations in synaptic versus
      extrasynaptic NMDA receptors in both direct and indirect pathway MSNs in late HD,
      which may contribute to the dysfunction and degeneration in both pathways. 

PMID- 24894509
TI  - Mandibular kinematic changes after unilateral cross-bite with lateral shift
      correction.
AB  - The aim of this randomised prospective study was to evaluate the effects of slow
      maxillary expansion with expansion plates and Hyrax expanders on the kinematics
      of the mandible after cross-bite correction. Thirty children (15 boys and 15
      girls), aged 7.1-11.8, with unilateral cross-bite and functional shift were
      divided into two groups: expansion plate (n = 15) and Hyrax expander (n = 15).
      Thirty children with normal occlusion (14 boys and 16 girls, aged 7.3-11.6)
      served as control group. The maximum vertical opening, lateral mandibular shift
      (from maximum vertical opening to maximum intercuspation, from rest position to
      maximum intercuspation and from maximum vertical opening to rest position) and
      lateral excursions were recorded before and 4 months after treatment. After
      treatment, the expansion plate group showed a greater lateral shift from rest
      position to maximum intercuspation than did the control group. The expansion
      plate patients also presented greater left/contralateral excursion than did the
      control group. Comparisons of changes after treatment in the cross-bite groups
      showed significant decreases in the lateral shift from the maximum vertical
      opening to maximum intercuspation and from the maximum vertical opening to rest
      position, a significant increase in the homolateral excursion and a significant
      decrease in the contralateral excursion in the Hyrax expander group, whereas no
      significant differences were found in the expansion plate group. In conclusion,
      the Hyrax expander showed better results than did the expansion plate. The Hyrax
      expander with acrylic occlusal covering significantly improved the mandibular
      lateral shift and normalised the range of lateral excursion. 

PMID- 24894508
TI  - Asian-White disparities in short sleep duration by industry of employment and
      occupation in the US: a cross-sectional study.
AB  - BACKGROUND: Although short sleep is associated with an increased risk of
      morbidity as well as mortality and has been shown to vary by industry of
      employment and occupation, little is known about the relationship between work
      and sleep among Asian Americans. METHODS: Using a nationally representative
      sample of US adults (n = 125,610) in the National Health Interview Survey from
      2004-2011, we estimated prevalence ratios for self-reported short sleep duration
      (<7 hours) in Asians compared to Whites by industry of employment and occupation
      using adjusted Poisson regression models with robust variance. RESULTS: Asians
      were more likely to report short sleep duration than Whites (33 vs. 28%, p <
      0.001), and the Asian-White disparity was widest in finance/information and
      healthcare industries. Compared to Whites after adjustments, short sleep was also
      more prevalent among Asians employed in Public administration (PR = 1.35 [95% CI:
      1.17,1.56]), Education (PR = 1.29 [95% CI: 1.08,1.53]), and
      Professional/Management (PR = 1.18 [95% CI: 1.03,1.36]). Short sleep, however,
      was lower among Asians in Accommodation/Food (PR = 0.81 [95% CI: 0.66, 0.99])
      with no difference in Retail. In professional and support-service occupations,
      short sleep was higher among Asians, but was not different among laborers.
      CONCLUSIONS: U.S. Asian-White disparities in short sleep varied by industries,
      suggesting a need to consider both race and occupational characteristics to
      identify high-risk individuals.

PMID- 24894510
TI  - N-3 fatty acid intake altered fat content and fatty acid distribution in chicken
      breast muscle, but did not influence mRNA expression of lipid-related enzymes.
AB  - BACKGROUND: The conversions of the n-3 and n-6 fatty acid of plant origin to the
      C20 and C22 very long chain fatty acids (LCPUFAs) is regulated by several
      cellular enzymes such as elongases and desaturases. METHODS: Sixty-five male one
      day old chickens (Ross 308) were randomly divided into four groups and given one
      of four diets; with or without linseed oil (LO), (the diets contained equal
      amounts of fat) and with low or high selenium (Se). Final body weight, amount of
      Se and fat in breast muscle, fatty acid profile, and gene expression for fatty
      acid desaturases (Fads1, Fads2, Fads9), HMG-CoA reductase, Acyl-CoA oxidase
      (Acox), carnitine palmitoyl transferase1 (Cpt1), superoxide dismutase (Sod) and
      glutathione peroxidase4 (Gpx4) were analyzed in all animals, and Gpx activity in
      whole blood was determined. RESULTS: mRNA expression of elongases and desaturases
      in chicken breast muscle was not affected by feed rich in C18:3n-3. The highly
      positive correlation between amount of fat in breast muscle and the
      product/precursor indices of monounsaturated fatty acid synthesis, and the
      negative correlation between muscle fat and indices of LCPUFA synthesis should be
      further studied. CONCLUSION: mRNA expression in chicken breast muscle of
      elongases and desaturases was not affected by feed rich in C18:3n-3. The highly
      positive correlation between amount of fat in breast muscle and the
      product/precursor indices of monounsaturated fatty acid synthesis, and the
      negative correlation between muscle fat and indices of LCPUFA synthesis should be
      further studied.

PMID- 24894511
TI  - Association of cellular and molecular alterations in Leydig cells with apoptotic
      changes in germ cells from testes of Graomys griseoflavus*Graomys centralis male
      hybrids.
AB  - Spermatogenesis is disrupted in Graomys griseoflavus*Graomys centralis male
      hybrids. This study was aimed to determine whether morphological alterations in
      Leydig cells from hybrids accompany the arrest of spermatogenesis and cell death
      of germ cells and whether apoptotic pathways are also involved in the response of
      these interstitial cells. We used three groups of 1-, 2- and 3-month-old male
      animals: (1) G. centralis, (2) G. griseoflavus and (3) hybrids obtained by
      crossing G. griseoflavus females with G. centralis males. Testicular
      ultrastructure was analyzed by transmission electron microscopy. TUNEL was
      studied using an in situ cell death detection kit and the expression of apoptotic
      molecules by immunohistochemistry. The data confirmed arrest of spermatogenesis
      and intense apoptotic processes of germ cells in hybrids. These animals also
      showed ultrastructural alterations in the Leydig cells. Fas, FasL and calbindin
      D28k overexpression without an increase in DNA fragmentation was detected in the
      Leydig cells from hybrids. In conclusion, the sterility of Graomys hybrids occurs
      with ultrastructural changes in germ and Leydig cells. The enhancement of Fas and
      FasL is not associated with cell death in the Leydig cells. Probably the
      apoptosis in these interstitial cells is inhibited by the high expression of the
      antiapoptotic molecule calbindin D28k. 

PMID- 24894513
TI  - Intraductal ultrasound for high-risk patients: when will the last be first?

PMID- 24894514
TI  - Impaired viscosity of gastric secretion and its mucin content as potential
      contributing factors to the development of chronic constipation.
AB  - BACKGROUND: The alimentary tract mucosa continuously releases mucus-rich
      secretion. Mucin, the major component of mucus, determines its viscosity and
      provides lubrication for the luminal content of indigestible food particles.
      AIMS: To measure mucin secretion rate and its viscosity in patients with chronic
      constipation (CC) and in asymptomatic volunteers. METHODS: Nineteen patients with
      symptoms of CC and 19 controls were included in the study. Mucin secretion and
      viscosity were assessed in aspirated gastric juice in basal conditions and after
      stimulation with pentagastrin (1 h each). Mucin content was tested by PAS
      methodology. Viscosity was measured using cone/plate digital viscometer. RESULTS:
      Mucin secretion rates in basal and stimulated conditions in controls were 65 and
      42 % higher than in patients with CC (P < 0.05 and P < 0.001, respectively).
      Basal viscosity in controls was 48 % higher than in CC (P < 0.05) at the lowest
      and 55 % higher (P < 0.05) at the middle velocities. Viscosity in pentagastrin
      stimulated conditions in controls was 71 % higher than in CC (P < 0.01) at the
      lowest and 35 % higher (P < 0.05) at the middle velocities. CONCLUSIONS: (1) The
      significantly lower rate of soluble mucin secretion in patients with CC than in
      normal volunteers may reflect impairment in mucin-related lubrication. (2)
      Significantly lower viscosity of gastric secretion in patients with CC may result
      from the lower rate of mucin secretion and may also diminish lubrication within
      the alimentary tract. (3) This may potentially set the stage for the development
      of symptoms related to chronic constipation and open a new therapeutic avenue for
      this patient population.

PMID- 24894512
TI  - Hepatitis C virus infection and coronary artery disease risk: a systematic review
      of the literature.
AB  - BACKGROUND AND AIMS: While hepatitis C virus (HCV) infection has been implicated
      in increasing the risk of coronary artery disease (CAD), conflicting reports
      exist regarding this association. We performed a systematic review to further
      investigate this association. METHODS: We conducted a PubMed search of original
      research articles from January 1, 1995 to June 30, 2013 to identify case-control
      and cohort studies evaluating the association between HCV and CAD using keyword
      terms ["hepatitis c" or "HCV"] and ["coronary artery disease" or "heart disease"
      or "atherosclerosis."] The primary CAD-related endpoints included myocardial
      infarction, congestive heart failure, need for coronary artery bypass grafting,
      or transluminal percutaneous coronary angioplasty. Binary outcomes are reported
      as odds ratios (OR) with 95 % confidence interval (CI). RESULTS: We identified
      five studies (four cohort studies and one case-control study) that met our
      inclusion criteria. A significant association between HCV and CAD was
      demonstrated in one cohort study (adjusted HR 1.27; 95 % CI 1.22-1.31). One
      cohort study demonstrated a decreased risk of CAD associated with HCV (adjusted
      OR 0.74; 95 % CI 0.71-0.76). The remaining studies did not find a significant
      association between HCV and risk of CAD. CONCLUSIONS: The current systematic
      review demonstrates that the association between HCV and CAD remains unclear. We
      need more large, long-term cohort studies with clear definitions of patient
      population and endpoints to better ascertain the association between HCV and CAD.

PMID- 24894515
TI  - Alternative models for estimating the radiotherapy retreatment dose for the
      spinal cord.
AB  - PURPOSE: To review the available experimental animal and patient data on response
      of the spinal cord to re-irradiation in order to identify appropriate data sets
      to investigate the clinical potential of models that would allow evaluation of
      the increase in the retreatment dose with elapsed time from the initial exposure.
      MATERIALS/METHODS: Analysis of published data on irradiated rat and primate
      spinal cord identified results for the rat cervical spinal cord that could be
      compared, where the development of myelopathy was caused by selective white
      matter necrosis. This data, although limited, provide some important insights.
      Two models, derived from simple differential equations, provide a time- and dose
      dependency for recovery and could be fitted to these data. These models predict
      the remaining tolerance, in a phase space above the line that connects the 100%
      biological effectiveness (BEDTOL) tolerance dose of the first and second
      treatment courses when these are plotted together. A third, much simpler, linear
      model, assumed that recovery was time but not initial dose dependent. RESULTS:
      The experimental results showed a non-linear time dependency for the change in
      biological effectiveness (BED) of the re-irradiation dose. Comparison of the
      three different models paid particular attention to changes in the re-irradiation
      dose, when the initial radiation dose was either low or high. For each model,
      cautious data interpretations were also introduced to reduce the effects of the
      near completeness of recovery with time derived from the important experiments
      with primates, which include few data points. Model 1 predicts the least recovery
      following low initial doses, but with greater recovery following larger initial
      doses. Model 2 allowed no further irradiation after an initial full tolerance
      dose, but also greater than expected recovery following the use of smaller
      priming doses. Model 3 gives unrealistically high doses when used after an
      initial full tolerance irradiation dose. CONCLUSIONS: These results show that it
      is possible to model these time-dependent relationships for the spinal cord and
      that Model 1 is probably the most realistic, especially when it is used
      conservatively. To give greater confidence as to which of the three presented
      methods is best, further experiments and/or more analysis of human data are
      necessary. In the meantime clinicians will need to exert caution and judgement as
      to the choice of the re-irradiation BED, bearing in mind the other clinical
      factors that influence radio-tolerance. Further research is necessary to provide
      the safest recommendations and best clinical outcomes. Some suggestions as to
      what needs to be done are given.

PMID- 24894516
TI  - Global protein-protein interaction network of rice sheath blight pathogen.
AB  - Rhizoctonia solani is the major pathogenic fungi of rice sheath blight. It is
      responsible for the most serious disease of rice (Oryza sativa L.) and causes
      significant yield losses in rice-growing countries. Identifying the protein
      protein interaction (PPI) maps of R. solani can provide insights into the
      potential pathogenic mechanisms and assign putative functions to unknown genes.
      Here, we exploited a PPI map of R. solani anastomosis group 1 IA (AG-1 IA) based
      on the interolog and domain-domain interaction methods. We constructed a core
      subset of high-confidence protein networks consisting of 6705 interactions among
      1773 proteins. The high quality of the network was revealed by comprehensive
      methods, including yeast two-hybrid experiments. Pathogenic interaction
      subnetwork, secreted proteins subnetwork, and mitogen-activated protein kinase
      (MAPK) cascade subnetwork and their interacting partners were constructed and
      analyzed. Moreover, to exactly predict the pathogenic factors, the expression
      levels of the interaction proteins were investigated by analyzing RNA sequences
      that consisted of samples from the entire infection progress. The PPIs offer an
      exceptionally rich source of data that can be used to understand the gene
      functions and biological processes of this serious disease at the system level. 

PMID- 24894517
TI  - Psychoanalysis, religion and enculturation: reflections through the life of
      mother Teresa.
AB  - This paper explores the question of whether psychoanalysis can help those who
      adhere to a worldview that is non-psychoanalytic or even anti-psychoanalytic. It
      answers this question by comparing the psychoanalytic understanding of suffering
      with that of the Catholic faith, through the latter's idea of the 'dark night of
      the soul'. The life of Mother Teresa is taken as an illustration of the dark
      night and how it may be responded to by the faithful. Similarities and
      differences between the two approaches are pointed out. Finally, it is suggested
      that psychoanalytic perspectives may enrich the inner lives of those living by a
      religious worldview, without necessarily diluting that worldview. Further,
      religious counsellors too may benefit from an understanding of psychoanalytic
      perspectives. 

PMID- 24894518
TI  - Striated muscle hamartoma in a newborn.
AB  - Striated muscle hamartoma (SMH) is an uncommon benign lesion, that is usually
      congenital, polypoid, and primarily located on the head and neck. The key
      histopathologic sign is the existence of individualized fascicles of striated
      muscle affecting the dermis and subcutaneous fat tissue. Here we report the case
      of a newborn girl with an SMH, who presented with a congenital infiltrated plaque
      on her chin without any other associations. 

PMID- 24894519
TI  - A novel electrochemical DNA biosensor construction based on layered CuS-graphene
      composite and Au nanoparticles.
AB  - A novel CuS-graphene (CuS-Gr) composite was synthesized to achieve excellent
      electrochemical properties for application as a DNA electrochemical biosensor.
      CuS-Gr composite was prepared by a hydrothermal method, in which two-dimensional
      graphene served as a two-dimensional conductive skeleton to support CuS
      nanoparticles. A sensitive electrochemical DNA biosensor was fabricated by
      immobilizing single-stranded DNA (ss-DNA) labeled at the 5' end using 6-mercapto
      1-hexane (HS-ssDNA) on the surface of Au nanoparticles (AuNPs) to form ssDNA-S
      AuNPs/CuS-Gr, and hybridization sensing was done in phosphate buffer. Cyclic
      voltammetry and electrochemical impedance spectroscopy were performed for the
      characterization of the modified electrodes. Differential pulse voltammetry was
      applied to monitor the DNA hybridization using an [Fe(CN)6](3-/4-) solution as a
      probe. Under optimum conditions, the biosensor developed exhibited a good linear
      relationship between the current and the logarithm of the target DNA
      concentration ranging from 0.001 to 1 nM, with a low detection limit of 0.1 pM
      (3sigma/S). The biosensor exhibited high selectivity to differentiate one-base
      mismatched DNA and three-base-mismatched DNA. The results indicated that the
      sensing platform based on CuS-Gr provides a stable and conductive interface for
      electrochemical detection of DNA hybridization, and could easily be extended to
      the detection of other nucleic acids. 

PMID- 24894520
TI  - Phenotyping of CYP450 in human liver microsomes using the cocktail approach.
AB  - The cocktail approach is an advantageous strategy used to monitor the activities
      of several cytochromes P450 (CYPs) in a single test to increase the throughput of
      in vitro phenotyping studies. In this study, a cocktail mixture was developed
      with eight CYP-specific probe substrates to simultaneously evaluate the activity
      of the most important CYPs, namely, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19,
      CYP2D6, CYP2E1, and the CYP3A subfamily. After cocktail incubation in the
      presence of human liver microsomes (HLMs), the eight selected substrates and
      their specific metabolites were analyzed by ultra-high-pressure liquid
      chromatography and electrospray ionization quadrupole time-of-flight mass
      spectrometry. Qualitative and quantitative data were simultaneously acquired to
      produce an overview of the extended phase I biotransformation routes for each
      probe substrate in the HLMs and to generate phenotypic profiles of various HLMs.
      A comparison of the cocktail strategy with an individual substrate assay for each
      CYP produced similar results. Moreover, the cocktail was tested on HLMs with
      different allelic variants and/or in the presence of selective inhibitors. The
      results were in agreement with the genetic polymorphisms of the CYPs and the
      expected effect of the alterations. All of these experiments confirmed the
      reliability of this cocktail assay for phenotyping of the microsomal CYPs. 

PMID- 24894522
TI  - Effects of strain and light intensity on growth performance and carcass
      characteristics of broilers grown to heavy weights.
AB  - Effects of genetic strain and light intensity on growth performance and carcass
      characteristics of broilers grown to heavy weights were investigated. The
      experimental design was a randomized complete block design. Treatment structure
      was a 2 * 5 factorial arrangement with the main factors being strain (Ross * Ross
      308, Ross * Ross 708) and light intensity (25, 10, 5, 2.5, and 0.2 lx) with trial
      as replicates. In each of the 5 trials, chicks of 2 different strains of the same
      commercial hatchery were equally and randomly distributed into 10 environmentally
      controlled rooms (5 rooms/strain) at 1 d of age at 50% RH. Each room was randomly
      assigned 1 of 5 light intensities from 22 to 56 d of age. Feed and water were
      provided ad libitum. Birds and feed were weighed on 0, 14, 28, 42, and 56 d of
      age for growth performance. Humoral immune response was determined on d 28,
      whereas ocular and blood samples were performed on d 42 and 55, respectively. On
      d 56, 20 (10 males and 10 females) birds/strain from each room were processed to
      determine weights and yields. Genetic strain was significant (P <= 0.05) for most
      of the examined variables, where Ross * Ross 308 had better growth performance
      and meat yield in comparison with Ross * Ross 708. Although, there was no main
      effect of light intensity on growth performance and meat yield, results indicated
      that birds under 10 and 5 lx intensities showed slightly better growth
      performance and meat yield compared with birds under 25, 2.5, and 0.2 lx in both
      strains. There was no effect of strain and light intensity on ocular indices,
      immune response, plasma corticosterone levels, and mortality. This study shows
      the positive influence on profits to commercial poultry facilities that are using
      a low lighting environment to reduce energy cost, optimize feed conversion, and
      maximize production without compromising the welfare of the broilers. 

PMID- 24894523
TI  - Nutritional value, performance, carcass quality, visceral organ size, and blood
      clinical chemistry of broiler chicks fed 30% tannin-free fava bean diets.
AB  - Two experiments were conducted to evaluate the chemical and nutritional values of
      5 tannin-free fava bean (FB) cultivars (FB9, FB10, FB13, FB17, and FB24) on
      growth, visceral organ size, and blood clinical chemistry of broiler chicks fed a
      corn-soybean meal 48 (SBM48) diet containing 30% tannin-free FB. In the first
      experiment, 49 Hy-line roosters, 55 wk of age, were individually precision-fed 30
      g of each FB cultivar and soybean meal 44 (SBM44). Protein, methionine, and
      lysine contents of the FB seeds (0.005% tannin) were 27.7, 0.23, and 1.98% of DM,
      respectively. The AMEn of all FB cultivars was 2,839 kcal/kg and higher (P <
      0.05) than SBM44. The true lysine digestibility of FB10 (94.1) was higher (P <
      0.05) than FB9 (89.0%) and FB24 (89.2%), but comparable with the other fava
      beans. The FB cultivar's true methionine digestibilities were similar among each
      other and to SBM44. In a battery feeding trial, 6 corn-SBM48 diets containing 0
      (control) or 30% of FB9, FB10, FB13, FB17, or FB24 seeds were each fed to Ross
      308 1-wk-old male broiler chicks for 14 d. The determined FB nutrient values were
      used in formulating FB-containing diets. Birds fed FB-containing diets had better
      (P < 0.05) weight gain and feed conversion than those of the control. When
      compared with the control birds, relative weights of abdominal fat pad and liver
      were reduced (P < 0.05) by 30% inclusion of all dietary FB varieties, except for
      FB17 and FB13, respectively. Broiler chicks fed the FB13 diet had plasma
      thrombocyte and white blood cell (WBC) differential counts higher (P < 0.05) than
      those fed the FB10 diet and WBC count higher (P < 0.05) than the birds fed the
      FB17 diet. In conclusion, tannin-free FB was lower in protein, methionine, and
      lysine, but higher in AMEn, compared with SBM44. Moreover, FB seeds, especially
      FB10, can be included in a broiler chick diet with no adverse effects on
      performance, but FB13 increased WBC count. 

PMID- 24894521
TI  - Temporal dystrophic remodeling within the intrinsic cardiac nervous system of the
      streptozotocin-induced diabetic rat model.
AB  - INTRODUCTION: The pathogenesis of heart failure (HF) in diabetic individuals,
      called "diabetic cardiomyopathy", is only partially understood. Alterations in
      the cardiac autonomic nervous system due to oxidative stress have been
      implicated. The intrinsic cardiac nervous system (ICNS) is an important
      regulatory pathway of cardiac autonomic function, however, little is known about
      the alterations that occur in the ICNS in diabetes. We sought to characterize
      morphologic changes and the role of oxidative stress within the ICNS of diabetic
      hearts. Cultured ICNS neuronal cells from the hearts of 3- and 6-month old type 1
      diabetic streptozotocin (STZ)-induced diabetic Sprague-Dawley rats and age
      matched controls were examined. Confocal microscopy analysis for protein gene
      product 9.5 (PGP 9.5) and amino acid adducts of (E)-4-hydroxy-2-nonenal (4-HNE)
      using immunofluorescence was undertaken. Cell morphology was then analyzed in a
      blinded fashion for features of neuronal dystrophy and the presence of 4-HNE
      adducts. RESULTS: At 3-months, diabetic ICNS neuronal cells exhibited 30% more
      neurite swellings per area (p = 0.01), and had a higher proportion with
      dystrophic appearance (88.1% vs. 50.5%; p = <0.0001), as compared to control
      neurons. At 6-months, diabetic ICNS neurons exhibited more features of dystrophy
      as compared to controls (74.3% vs. 62.2%; p = 0.0448), with 50% more neurite
      branching (p = 0.0015) and 50% less neurite outgrowth (p = <0.001). Analysis of 4
      HNE adducts in ICNS neurons of 6-month diabetic rats demonstrated twice the
      amount of reactive oxygen species (ROS) as compared to controls (p = <0.001).
      CONCLUSION: Neuronal dystrophy occurs in the ICNS neurons of STZ-induced diabetic
      rats, and accumulates temporally within the disease process. In addition,
      findings implicate an increase in ROS within the neuronal processes of ICNS
      neurons of diabetic rats suggesting an association between oxidative stress and
      the development of dystrophy in cardiac autonomic neurons.

PMID- 24894524
TI  - Dustbathing in food particles does not remove feather lipids.
AB  - Within the European Union, dustbathing material in cage-housing systems for
      laying hens became compulsory in 2012. In practice, most producers use food
      particles as litter substrate. The feed is dropped in small amounts on scratching
      mats by an automatic transporting system. However, because dustbathing behavior
      is meant to remove stale lipids from hens' plumage, food particles may not be a
      suitable substrate due to their fat content. This study analyzes feather lipid
      concentration (FLC) of laying hens with access to food particles (F) or
      lignocellulose (L) as litter substrates. In each of 2 identical trials, 84 laying
      hens of 2 genotypes (Lohmann Selected Leghorn, Lohmann Brown) were kept in 12
      compartments (7 hens each). Compartments were equipped with a grid floor and
      additionally contained a closed dustbathing tray holding F or L. Feather samples
      (150 feathers) were taken 2 times throughout the experiment. At 23 wk of age, 4
      hens per compartment were sampled after they were allowed pair-wise access to a
      dustbath for 2.5 h and 3 hens were sampled without access to a dustbathing tray
      (control). After 10 wk of free access to the dustbathing trays, all hens were
      sampled again. In trial 2, an additional third sampling was made after dustbaths
      had been closed again for 6 wk. Here, 6 hens per compartment were sampled
      immediately before and after a dustbath. Dustbathing in F resulted in higher FLC
      compared with L and control (P < 0.001), whereas no significant difference was
      found between L and control (P = 0.103). When open access to litter was provided,
      hens had higher FLC in F compared with L (P < 0.001). The FLC immediately after
      dustbathing in F was higher compared with the level before dustbathing (P <
      0.001), whereas it was lower after dustbathing in L (P = 0.006). These results
      show that F are not suitable litter material for laying hens because they lead to
      lipid accumulation on the plumage. 

PMID- 24894525
TI  - Effect of corn silage and quantitative feed restriction on growth performance,
      body measurements, and carcass tissue composition in White Koluda W31 geese.
AB  - The objective of this study was to determine the effect of corn silage and
      quantitative feed restriction on BW, ADG, feed conversion, and carcass
      composition of White Koluda W31 geese. Two diets were fed during the rearing
      period from 22 to 98 d of age: 1) a commercial diet ad libitum, and 2) restricted
      amounts of a commercial diet and corn silage ad libitum. Each treatment had 2
      replicates of 16 birds each. From 99 to 119 d of age, all birds were fattened
      with whole oat grain alone. Incorporation of corn silage reduced weight gains and
      caused statistically significant differences in BW at the end of the rearing
      period (14 wk, 6,625.0 vs. 6,050.0 g; P < 0.05). Experimental geese showed
      compensatory growth during the oat fattening period and the BW of geese from both
      groups was similar at the end of the study (17 wk, 7,675.1 vs. 7,467.9 g; P >
      0.05). Daily weight gains varied with week of growth, being lowest at 12 wk of
      age. Birds fed the commercial diet and corn silage had a significantly longer
      trunk (29.2 vs. 31.0 cm, P < 0.05) and shorter shanks (10.0 vs. 9.4 cm, P < 0.05)
      at 8 wk, and significantly smaller chest circumference (54.7 vs. 51.9 cm, P <
      0.05) at the end of 14 wk. At the end of oat feeding (17 wk), geese receiving
      silage had significantly longer trunk and drumstick compared with geese fed
      commercial diets alone. The carcasses of 17-wk-old experimental geese contained
      more breast and leg muscles (%), and less skin with subcutaneous fat from breast
      and legs compared with control birds. Significant differences were only noted
      between the groups in dressing percentage (65.0 vs. 74.7%, P < 0.05) and
      proportion of skin with subcutaneous fat from breast (8.9 vs. 7.8%, P < 0.05).
      Dilution of the diet for young fattening geese with whole-crop corn silage had a
      positive effect on production economics and carcass composition. 

PMID- 24894526
TI  - Effects of breeder feeding restriction programs and incubation temperatures on
      progeny footpad development.
AB  - Footpad dermatitis begins early in life, and there is evidence of individual
      susceptibility. An experiment was conducted to evaluate the carryover effects of
      breeder feed restriction programs and incubation temperatures (TEM) on progeny
      footpad development at hatch, and 7 and 22 d. Cobb 500 fast feathering breeders
      were subjected to 2 dietary feed restriction programs during rearing: skip-a-day
      (SAD) and every-day feeding (EDF). At 60 wk of age, eggs from each group were
      collected and incubated according to 2 TEM, standard (S) eggshell temperature
      (38.1 degrees C) and early-low late-high (LH). This second profile had low (36.9
      degrees C) eggshell temperature for the first 3 d, and standard temperature until
      the last 3 d when eggs were subjected to elevated (38.9 degrees C) eggshell
      temperature. At hatch, 15 chicks from each treatment combination were sampled to
      obtain footpads for histological analysis. Seventy-two chicks per treatment were
      placed in 48 cages (6/cage), and raised to 22 d. At 7 and 22 d, 1 and 2 chickens,
      respectively, were sampled for footpads. The BW and group feed intake were
      recorded to obtain BW gain and feed conversion ratio at 7 and 21 d. Histological
      analysis assessed thickness and total area of stratus corneum (SC), epidermis,
      and dermis, and total papillae height. Data were analyzed as randomized complete
      block design in a 2 * 2 factorial arrangement of treatments. There was a negative
      effect of LH TEM on performance at both ages. An interaction effect on SC area
      and papillae height was observed at hatch. Additionally, SAD treatment increased
      thickness and area of footpad dermis. At 7 d, the SC parameters of the SAD
      progeny were increased. Epidermis thickness was affected by treatment
      interaction. Furthermore, LH TEM decreased epidermis thickness and dermis area.
      At 22 d, interaction effects were observed in thickness and area of SC and
      epidermis. Incubation S TEM increased thickness and area of dermis. It was
      concluded that breeder feed restriction programs and incubation TEM profiles may
      have carryover effects on histomorphological traits of footpads.

PMID- 24894527
TI  - A pilot study of the genetic variation of phosphorus utilization in young
      Japanese quail (Coturnix japonica).
AB  - This study estimated the genetic variance components of P utilization in Japanese
      quail. A parental generation was assembled from an unselected random-bred
      Japanese fattening quail line. Seven sires and 14 dams were randomly selected,
      and each sire was paired with 2 dams to produce full and half sibs. A total of
      200 unsexed 1-d-old quail with known pedigree were wing-banded and raised during
      the first 4 d posthatch in groups in floor pens on wood shavings and fed a
      preexperimental diet that was adequate in all nutrients. Starting on d 5, quail
      were individually housed in metabolic compartments on P-free filter paper. This
      started a balance trial with 5 d of adaption and 5 d of total excreta collection.
      During this balance period, all quail were fed a low-P (3.9 g/kg of DM) corn
      soybean meal-based diet with a Ca:P ratio of 1.6:1.0. Phosphorus and Ca
      utilization were determined individually using the difference in P or Ca intake
      and the total P or Ca excretion. The average P utilization was 72% and the
      average Ca utilization was 63%, each with very high variation. Heritabilities
      were estimated to be 0.09 (SE = 0.09) for P utilization and 0.09 (SE = 0.09) for
      Ca utilization. Heritabilities were close to the values reported in the
      literature for broilers and suggest that quail are suitable as a model animal.
      The SE of the heritability estimates were large. This implies that further
      studies with a larger sample size are needed to identify genetic and
      physiological mechanisms that influence P and Ca utilization in Japanese quail. 

PMID- 24894528
TI  - Exposure of embryos to cyclically cold incubation temperatures durably affects
      energy metabolism and antioxidant pathways in broiler chickens.
AB  - Cyclically cold incubation temperatures have been suggested as a means to improve
      resistance of broiler chickens to ascites; however, the underlying mechanisms are
      not known. Nine hundred eggs obtained from 48 wk Ross broiler breeders were
      randomly assigned to 2 incubation treatments: control I eggs were incubated at
      37.6 degrees C throughout, whereas for cold I eggs the incubation temperature was
      reduced by 1 degrees C for 6 h daily from 10 to 18 d of incubation. Thereafter,
      chickens were reared at standard temperatures or under cold exposure that was
      associated or not with a postnatal cold acclimation at d 5 posthatch. At hatch,
      hepatic catalase activity and malondialdehyde content were measured. Serum
      thyroid hormone and triglyceride concentrations, and muscle expression of several
      genes involved in the regulation of energy metabolism and oxidative stress were
      also measured at hatch and 5 and 25 d posthatch. Cold incubation induced
      modifications in antioxidant pathways with higher catalase activity, but lower
      expression of avian uncoupling protein 3 at hatch. However, long-term enhancement
      in the expression of avian uncoupling protein 3 was observed, probably caused by
      an increase in the expression of the transcription factor peroxisome proliferator
      activated receptor-gamma coactivator-1alpha. These effects were not
      systematically associated with an increase in serum triiodothyronine
      concentrations that were observed only in chickens exposed to both cold
      incubation and later acclimation at 5 d with cold rearing. Our results suggest
      that these conditions of cyclically cold incubation resulted in the long-term in
      changes in antioxidant pathways and energy metabolism, which could enhance the
      health of chickens reared under cold conditions. 

PMID- 24894529
TI  - Efficiency of hydrated sodium calcium aluminosilicate to ameliorate the adverse
      effects of graded levels of aflatoxin B1 in broiler chicks.
AB  - The objective of this study was to evaluate the efficiency of a hydrated sodium
      calcium aluminosilicate (HSCAS) adsorbent to ameliorate the adverse effects of
      0.5 to 2 mg of aflatoxin B1 (AFB1)/kg in broiler chicks. The study consisted of 8
      dietary treatments, including 4 concentrations of AFB1 (0, 0.5, 1, and 2 mg/kg)
      with or without HSCAS (0.5%) fed to 8 replicate cages per diet (6 males chicks
      per cage) from 0 to 21 d of age. Cumulative feed intake, BW gain (P < 0.0001),
      and G:F (P = 0.004) of birds fed the 2 mg of AFB1/kg of diet were significantly
      lower in comparison with birds fed 0 to 1 mg of AFB1/kg. Relative liver weight
      was increased in the 2 mg of AFB1/kg group (P < 0.0001). Dietary HSCAS improved
      cumulative BW gain (main effect P = 0.06), particularly from 14 to 21 d of age (P
      = 0.037). Dietary HSCAS also reversed the increase in relative liver weight for
      birds fed AFB1 (P = 0.019). Dietary AFB1 negatively affected major serum
      parameters (albumin, total protein, globulin, phosphorus, glucose, alkaline
      phosphatase, and creatine phosphokinase), whereas supplementation with HSCAS
      partially alleviated the affected serum biochemistry. In addition, serum
      complement activity and liver gene expression were negatively affected by 2 mg of
      AFB1/kg. The HSCAS supplement increased the liver expression of catalase and
      superoxide dismutase (P < 0.05). Results from this study indicate that dietary
      supplementation with HSCAS can effectively improve BW gain and partially
      ameliorate aflatoxicosis for broiler chicks fed AFB1-contaminated feeds. 

PMID- 24894530
TI  - The effects of electrical stunning methods on broiler meat quality: effect on
      stress, glycolysis, water distribution, and myofibrillar ultrastructures.
AB  - This study was designed to compare the effects of different stunning systems on
      the meat quality of broilers. This was done by investigating meat water-holding
      capacity, meat color, muscle glycogen, and lactate concentrations, as well as
      blood parameters, low-field nuclear magnetic resonance (NMR) transverse
      relaxation, and myofibrillar ultrastructures. A total of 160 broilers were
      divided into 4 treatment groups: a low-voltage stunning (LS) with a constant
      voltage of 15 V at 750 Hz for 10 s; a midvoltage stunning (MS) with a constant
      voltage of 50 V at 50 Hz for 10 s; a high-voltage stunning (HS) with a constant
      voltage of 100 V at 50 Hz for 5 s; and a control group with no stunning (NS).
      Blood samples were collected immediately after cutting the neck. Pectoralis major
      muscles were removed from the carcass after chilling and placed in ice. Breast
      muscle pH, meat color, glycogen, and lactate contents were determined at both 2
      and 24 h postmortem. Drip loss, cooking loss, pressing loss, cooked breast meat
      shear values, low-field NMR, and ultrastructures of myofibrils were determined 24
      h postmortem. The NS and MS treatments significantly increased (P < 0.05) blood
      plasma corticosterone, initial rate of glycolysis, and drip loss, and
      significantly reduced (P < 0.05) initial muscle pH and shear force values when
      compared with LS and HS. The results of low-field NMR reflect that NS and MS
      significantly decreased (P < 0.05) NMR transverse relaxation population 1 (T21)
      and increased (P < 0.05) NMR transverse relaxation population 2 (T22). The
      myofibrils of NS and MS samples showed significantly (P < 0.05) longer sarcomere
      length when compared with the LS and HS samples. The meat color, cooking loss,
      pressing loss, and final pH were not affected by the stunning methods. This study
      indicates that NS and MS treatments reduce meat water-holding capacity and
      decrease meat shear force when compared with LS and HS. 

PMID- 24894531
TI  - The effects of quercetin dietary supplementation on broiler growth performance,
      meat quality, and oxidative stability.
AB  - The present study was conducted to describe the effects of quercetin dietary
      supplementation, at levels of 0.5 and 1 g/kg of feed, on growth performance,
      internal organ weights, meat quality, and meat oxidative stability during storage
      of broiler chickens reared from hatching to 42 d of age. Body weight and
      cumulative feed intake were not affected by quercetin supplementation (P > 0.05).
      However, poorer feed conversion ratio values were obtained with increasing levels
      of dietary quercetin (P-linear < 0.05). Relative heart weight was significantly
      higher for chickens that were given quercetin in comparison with the controls (P
      < 0.05). The rest of the internal organ weights measured (liver, spleen, and fat
      pad) and meat quality traits were not affected by dietary supplementation with
      quercetin, except for meat lightness and redness. Meat oxidative stability,
      expressed as nanograms of malondialdehyde per gram of meat, was improved (P <
      0.05) during refrigerated storage for 3 and 9 d, when birds were fed quercetin at
      a level of 1 g/kg of feed. It is concluded that the incorporation of quercetin in
      broiler diets could prolong meat shelf life by reducing the rate of lipid
      oxidation, and increase relative heart weight, potentially contributing to
      improved animal health. 

PMID- 24894532
TI  - Infectious bronchitis virus in different avian physiological systems-a field
      study in Brazilian poultry flocks.
AB  - Avian infectious bronchitis is a highly contagious viral disease with economic
      effects on poultry agribusiness. The disease presents multi-systemic clinical
      signs (respiratory, renal, enteric, and reproductive) and is caused by one
      coronavirus (infectious bronchitis virus, IBV). Infectious bronchitis virus is
      classified into different serotypes and genotypes (vaccine strains and field
      variants). This study aimed to evaluate the occurrence of IBV in commercial
      poultry flocks from 3 important producing regions in Brazil and to determine the
      tropism of the main circulating genotypes to 3 different avian physiological
      systems (respiratory, digestive, urinary/reproductive). Clinical samples with
      suggestive signs of IBV infection were collected from 432 different poultry
      commercial flocks (198 from broilers and 234 from breeders). The total number of
      biological samples consisted of organ pools from the 3 above physiological
      systems obtained of farms from 3 important producing regions: midwest, northeast,
      and south. Infectious bronchitis virus was detected by reverse-transcription,
      real-time PCR of the 5' untranslated region. The results showed 179 IBV-positive
      flocks (41.4% of the flocks), with 107 (24.8%) from broilers and 72 (16.8%) from
      breeders. There were similar frequencies of IBV-positive flocks in farms from
      different regions of the country, most often in broilers (average 54%) compared
      with breeders (average 30.8%). reverse-transcription was more frequently detected
      in the digestive system of breeders (40%), and in the digestive (43.5%) and
      respiratory (37.7%) systems of broilers. Infectious bronchitis virus genotyping
      was performed by a reverse-transcription nested PCR and sequencing of the S1 gene
      from a selection of 79 IBV-positive flocks (45 from broilers and 34 from
      breeders). The majority of the flocks were infected with Brazilian variant
      genotype than with Massachusetts vaccine genotype. These results demonstrate the
      predominance of the Brazilian variant (mainly in the enteric tract) in commercial
      poultry flocks from 3 important producing regions in Brazil. 

PMID- 24894533
TI  - Tamsulosin versus tamsulosin plus tadalafil as medical expulsive therapy for
      lower ureteric stones: a randomized controlled trial.
AB  - OBJECTIVES: To compare the efficacy of tamsulosin versus tamsulosin plus
      tadalafil as medical expulsive therapy for lower ureteric stones. METHODS:
      Between January 2013 and December 2013, 244 patients presenting with distal
      ureteric stones (size 5-10 mm) were randomized equally to tamsulosin (group A) or
      tamsulosin plus tadalafil (group B). Therapy was given for a maximum of 4 weeks.
      Stone expulsion rate, time to stone expulsion, analgesic use, number of hospital
      visits for pain, follow up, endoscopic treatment and adverse effects of drugs
      were recorded. Statistical analyses were carried out using Student's t-test and
      the chi(2) -test. RESULTS: There was a statistically significant higher expulsion
      rate in group B compared with group A (83.6% vs 65.5%; P-value = 0.031) and a
      shorter time to expulsion (14.9 +/- 4.4 days vs 16.7 +/- 4.8 days; P-value =
      0.003). Statistically significant differences were noted in terms of the number
      of hospital visits and analgesic requirement in favor of group B. There was no
      serious adverse event. An improvement in erectile function was noted in patients
      of group B compared with those of group A. CONCLUSIONS: Medical expulsive therapy
      for distal ureteric stones using tamsulosin plus tadalafil is safe, effective and
      well tolerated. Furthermore, tadalafil provides the additional advantage of
      improving erectile dysfunction when this condition coexists with a lower ureteric
      stone.

PMID- 24894534
TI  - Application of GEANT4 simulation on calibration of HPGe detectors for cylindrical
      environmental samples.
AB  - The determination of radionuclide activity concentration requires a prior
      knowledge of the full-energy peak (FEP) efficiency at all photon energies for a
      given measuring geometry. This problem has been partially solved by using
      procedures based on Monte Carlo simulations, developed in order to complement the
      experimental calibration procedures used in gamma-ray measurements of
      environmental samples. The aim of this article is to apply GEANT4 simulation for
      calibration of two HPGe detectors, for measurement of liquid and soil-like
      samples in cylindrical geometry. The efficiencies obtained using a simulation
      were compared with experimental results, and applied to a realistic measurement.
      Measurement uncertainties for both simulation and experimental values were
      estimated in order to see whether the results of the realistic measurement fall
      within acceptable limits. The trueness of the result was checked using the known
      activity of the measured samples provided by IAEA. 

PMID- 24894535
TI  - Impaired NLRP3 inflammasome expression and function in atopic dermatitis due to
      Th2 milieu.
AB  - BACKGROUND: Atopic dermatitis (AD) and psoriasis patients are frequently
      colonized with Staphylococcus aureus (S. aureus) that produce the staphylococcal
      exotoxin alpha-toxin. However, only patients with AD suffer from bacterial
      superinfections with this pathogen, which implicates immunological differences in
      AD vs psoriasis in combating these bacteria. S. aureus recognition is partially
      mediated by intracellular nucleotide-binding oligomerization domain receptors
      (NLRs), which link alpha-toxin to caspase-1 activation through the formation of
      the NLRP3 inflammasome and to IL-1beta secretion. OBJECTIVE: To investigate (i)
      NLRP3 expression in the context of different T-helper cytokine milieus and (ii)
      its function in response to sublytic alpha-toxin stimulation in patients with AD
      and psoriasis compared with healthy controls. METHODS: NLRP3 expression and
      function were investigated in lesional AD and psoriasis skin as well as in
      primary keratinocytes (HPKs) and monocytes upon stimulation with Th1, Th2, Th17
      and Th22 cytokines or staphylococcal alpha-toxin, respectively, at the mRNA and
      protein (ELISA, immunohistochemistry and immunofluorescence) level. RESULTS:
      NLRP3 and caspase-1 expressions were reduced in lesional AD skin compared to
      psoriatic and healthy skin. IL-4, IL-5 and IL-13 downregulated NLRP3 and ASC,
      whereas interferon-gamma upregulated NLRP3 in HPKs. In monocytes, caspase-1
      expression was reduced by Th2 cytokines and enhanced by a Th1 milieu. Caspase-1
      dependent IL-1beta secretion was impaired in monocytes from patients with AD
      compared to patients with psoriasis and healthy controls by alpha-toxin
      stimulation following priming with lipoteichoic acid. CONCLUSION: Impaired NLRP3
      expression and function may partially explain how skin colonization and infection
      with S. aureus can contribute to chronic skin inflammation in AD.

PMID- 24894536
TI  - USP8 controls the trafficking and sorting of lysosomal enzymes.
AB  - The endosomal deubiquitylase USP8 has profound effects on endosomal morphology
      and organisation. Previous reports have proposed both positive (EGFR, MET) and
      negative roles in the down-regulation of receptors (Frizzled, Smoothened). Here
      we report an additional influence of USP8 on the retromer-dependent shuttling of
      ci-M6PR between the sorting endosome and biosynthetic pathway. Depletion of USP8
      leads to a steady state redistribution of ci-M6PR from the Trans-Golgi Network
      (TGN) to endosomal compartments. Consequently we observe a defect in sorting of
      lysosomal enzymes, evidenced by increased levels of unprocessed Cathepsin D,
      which is secreted into the medium. The normal distribution of receptor can be
      restored by expression of siRNA-resistant USP8 but not by a catalytically
      inactive mutant or a truncated form, lacking a MIT domain required for endosomal
      localisation. We suggest that effects of USP8 depletion may reflect the loss of
      ESCRT-0 components which associate with retromer components Vps35 and SNX1,
      whilst failure to efficiently deliver lysosomal enzymes may also contribute to
      the observed block in receptor tyrosine kinase degradation. 

PMID- 24894537
TI  - Giant pelvic angiomyofibroblastoma: case report and literature review.
AB  - Angiomyofibroblastoma (AMF) is a rare, benign, soft-tissue tumor, which
      predominantly occurs in the vulvovaginal region of middle-aged women. It is
      clinically important to distinguish an AMF from other stromal cell lesions. Here,
      we report the case of a 32-year-old woman with a rare, giant pelvic AMF, which
      showed a benign clinical course. The tumor was located in the cul-de-sac of
      Douglas. It was well demarcated, hypocellular, edematous and composed of spindle
      shaped and oval stromal cells aggregating around thin-walled blood vessels. The
      tumor cells had abundant eosinophilic cytoplasm, and expressed estrogen
      receptors, progesterone receptors and desmin. Mitotic figures were absent. It is
      important to distinguish AMFs from aggressive angiomyxomas because both occur at
      similar sites but show different clinical behaviors. Most AMFs and aggressive
      angiomyxomas have the same immunohistochemical phenotype. The well-circumscribed
      borders of AMF are the most important characteristic that distinguish it from
      aggressive angiomyxomas. AMFs rarely recur after complete surgical excision.
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5510813471244189.

PMID- 24894538
TI  - Illumina sequencing-based analyses of bacterial communities during short-chain
      fatty-acid production from food waste and sewage sludge fermentation at different
      pH values.
AB  - Short-chain fatty acids (SCFAs) can be produced by primary and waste activated
      sludge anaerobic fermentation. The yield and product spectrum distribution of
      SCFAs can be significantly affected by different initial pH values. However, most
      studies have focused on the physical and chemical aspects of SCFA production by
      waste activated sludge fermentation at different pH values. Information on the
      bacterial community structures during acidogenic fermentation is limited. In this
      study, comparisons of the bacterial communities during the co-substrate
      fermentation of food wastes and sewage sludge at different pH values were
      performed using the barcoded Illumina paired-end sequencing method. The results
      showed that different pH environments harbored a characteristic bacterial
      community, including sequences related to Lactobacillus, Prevotella, Mitsuokella,
      Treponema, Clostridium, and Ureibacillus. The most abundant bacterial operational
      taxonomic units in the different pH environments were those related to
      carbohydrate-degrading bacteria, which are associated with constituents of co
      substrate fermentation. Further analyses showed that during organic matter
      fermentation, a core microbiota composed of Firmicutes, Proteobacteria, and
      Bacteroidetes existed. Comparison analyses revealed that the bacterial community
      during fermentation was significantly affected by the pH, and that the diverse
      product distribution was related to the shift in bacterial communities. 

PMID- 24894539
TI  - Phosphate solubilization potential and modeling of stress tolerance of
      rhizobacteria from rice paddy soil in northern Iran.
AB  - The purposes of this study were to evaluate the phosphate solubilization activity
      of bacteria isolated from the rhizosphere of rice paddy soil in northern Iran,
      and to study the effect of temperature, NaCl and pH on the growth of these
      isolates by modeling. Three of the most effective strains from a total of 300
      isolates were identified and a phylogenetic analysis was carried out by 16S rDNA
      sequencing. The isolates were identified as Pantoea ananatis (M36), Rahnella
      aquatilis (M100) and Enterobacter sp. (M183). These isolates showed multiple
      plant growth-promoting attributes such as phosphate solubilization activity and
      indole-3-acetic acid (IAA) production. The M36, M100 and M183 isolates were able
      to solubilize 172, 263 and 254 ug ml(-1) of Ca3(PO4)2 after 5 days of growth at
      28  degrees C and pH 7.5, and to produce 8.0, 2.0 and 3.0 MUg ml(-1) of IAA when
      supplemented with L-tryptophan (1 mg ml(-1)) for 72 h, at 28  degrees C and pH
      7.0, respectively. The solubilization of insoluble phosphate was associated with
      a drop in the pH of the culture medium and there was an inverse relationship
      between pH and solubilized P (r = -0.98, P < 0.0952). There were no significant
      differences among isolates in terms of acidity tolerance based on their
      confidence limits as assessed by segmented model analysis and all isolates were
      able to grow at pH 4.3-11 (with optimum at 7.0-7.5). Based on a sigmoidal trend
      of a three-parameter logistic model, the salt concentration required for 50 %
      inhibition was 8.15, 6.30 and 8.23 % NaCl for M36, M100 and M183 isolates,
      respectively. Moreover, the minimum and maximum growth temperatures estimated by
      the segmented model were 5.0 and 42.75  degrees C for M36, 12.76 and 40.32 
      degrees C for M100, and 10.63 and 43.66  degrees C for M183. The three selected
      isolates could be deployed as inoculants to promote plant growth in an
      agricultural environment.

PMID- 24894540
TI  - Metabolic engineering of Escherichia coli to enhance shikimic acid production
      from sorbitol.
AB  - Shikimic acid (SA) is the key synthetic material of Oseltamivir, which is an
      effective drug for the prevention and treatment of influenza. In this study, to
      block the downstream metabolic pathway of SA, the shikimate kinase isoenzyme
      genes aroK and aroL were deleted by Red recombination. Moreover, the key enzyme
      genes aroG, aroB, tktA and aroE of SA pathway were co-expressed by constructing
      the recombinant vector pETDuet-GBAE. As a result, SA production of E. coli
      BW25113 (?aroL/aroK, DE3)/pETDuet-GBAE reached 1,077.6 mg/l when low amounts of
      sorbitol (5 g/l) were fed in shake flasks. The yield was 3.7 times that when
      glucose was used (P < 0.05). The results showed that sorbitol was an optimized
      carbon source for the high efficient accumulation of SA for the first time, which
      was applicable to use in the industry for high yields and low consumption.

PMID- 24894542
TI  - Isolation and culture of adult mouse cardiomyocytes for cell signaling and in
      vitro cardiac hypertrophy.
AB  - Technological advances have made genetically modified mice, including transgenic
      and gene knockout mice, an essential tool in many research fields. Adult
      cardiomyocytes are widely accepted as a good model for cardiac cellular
      physiology and pathophysiology, as well as for pharmaceutical intervention.
      Genetically modified mice preclude the need for complicated cardiomyocyte
      infection processes to generate the desired genotype, which are inefficient due
      to cardiomyocytes' terminal differentiation. Isolation and culture of high
      quantity and quality functional cardiomyocytes will dramatically benefit
      cardiovascular research and provide an important tool for cell signaling
      transduction research and drug development. Here, we describe a well-established
      method for isolation of adult mouse cardiomyocytes that can be implemented with
      little training. The mouse heart is excised and cannulated to an isolated heart
      system, then perfused with a calcium-free and high potassium buffer followed by
      type II collagenase digestion in Langendorff retrograde perfusion mode. This
      protocol yields a consistent result for the collection of functional adult mouse
      cardiomyocytes from a variety of genetically modified mice. 

PMID- 24894541
TI  - Impact of self-reported gastroesophageal reflux disease in subjects from COPDGene
      cohort.
AB  - BACKGROUND: The coexistence of gastroesophageal reflux disease (GERD) and COPD
      has been recognized, but there has been no comprehensive evaluation of the impact
      of GERD on COPD-related health status and patient-centered outcomes. METHODS:
      Cross-sectional and longitudinal study of 4,483 participants in the COPDGene
      cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained
      by questionnaire. Clinical features, spirometry and imaging were compared between
      COPD subjects without versus with GERD. We evaluated the relationship between
      GERD and symptoms, exacerbations and markers of microaspiration in univariate and
      multivariate models. Associations were additionally tested for the confounding
      effect of covariates associated with a diagnosis of GERD and the use of proton
      pump inhibitor medications (PPIs). To determine whether GERD is simply a marker
      for the presence of other conditions independently associated with worse COPD
      outcomes, we also tested models incorporating a GERD propensity score. RESULTS:
      GERD was reported by 29% of subjects with female predominance. Subjects with GERD
      were more likely to have chronic bronchitis symptoms, higher prevalence of prior
      cardiovascular events (combined myocardial infarction, coronary artery disease
      and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more
      severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life
      (QOL) scores (St. George's Respiratory Questionnaire (SGRQ) total score 41.8 vs.
      34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In
      multivariate models, a significant relationship was detected between GERD and
      SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline
      (>=2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean
      follow-up time of two years, GERD was also associated with frequent (>=2/year
      exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI
      interactions and a GERD propensity score were included. PPI use was associated
      with frequent exacerbator phenotype, but did not meaningfully influence the GERD
      exacerbation association. CONCLUSIONS: In COPD the presence of physician
      diagnosed GERD is associated with increased symptoms, poorer QOL and increased
      frequency of exacerbations at baseline and during follow-up. These associations
      are maintained after controlling for PPI use. The PPI-exacerbations association
      could result from confounding-by-indication.

PMID- 24894544
TI  - Analysis of release kinetics of ocular therapeutics from drug releasing contact
      lenses: Best methods and practices to advance the field.
AB  - Several methods have been proposed to achieve an extended and controlled release
      of ocular therapeutics via contact lenses; however, the experimental conditions
      used to study the drug release vary greatly and significantly influence the
      release kinetics. In this paper, we examine variations in the release conditions
      and their effect on the release of both hydrophilic and hydrophobic drugs
      (ketotifen fumarate, diclofenac sodium, timolol maleate and dexamethasone) from
      conventional hydrogel and silicone hydrogel lenses. Drug release was studied
      under different conditions, varying volume, mixing rates, and temperature. Volume
      had the biggest effect on the release profile, which ironically is the least
      consistent variable throughout the literature. When a small volume (2-30 mL) was
      used with no forced mixing and solvent exchange every 24 h, equilibrium was
      reached promptly much earlier than solvent exchange, significantly damping the
      drug release rate and artificially extending the release duration, leading to
      false conclusions. Using a large volume (200-400 mL) with a 30 rpm mixing rate
      and no solvent exchange, the release rate and total mass released was
      significantly increased. In general, the release performed in small volumes with
      no force mixing exhibited cumulative mass release amounts of 3-12 times less than
      the cumulative release amounts in large volumes with mixing. Increases in mixing
      rate and temperature resulted in relatively small increases of 1.4 and 1.2 times,
      respectively in fractional mass released. These results strongly demonstrate the
      necessity of proper and thorough analysis of release data to assure that
      equilibrium is not affecting release kinetics. This is paramount for comparison
      of various controlled drug release methods of therapeutic contact lenses,
      validation of the potential of lenses as an efficient and effective means of drug
      delivery, as well as increasing the likelihood of only the most promising methods
      reaching in vivo studies.

PMID- 24894543
TI  - Conserved recurrent gene mutations correlate with pathway deregulation and
      clinical outcomes of lung adenocarcinoma in never-smokers.
AB  - BACKGROUND: Novel and targetable mutations are needed for improved understanding
      and treatment of lung cancer in never-smokers. METHODS: Twenty-seven lung
      adenocarcinomas from never-smokers were sequenced by both exome and mRNA-seq with
      respective normal tissues. Somatic mutations were detected and compared with
      pathway deregulation, tumor phenotypes and clinical outcomes. RESULTS: Although
      somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor,
      the overlap mutations between the two were only a few to a couple of hundreds.
      The number of somatic mutations from either DNA or mRNA was not significantly
      associated with clinical variables; however, the number of overlap mutations was
      associated with cancer subtype. These overlap mutants were preferentially
      expressed in mRNA with consistently higher allele frequency in mRNA than in DNA.
      Ten genes (EGFR, TP53, KRAS, RPS6KB2, ATXN2, DHX9, PTPN13, SP1, SPTAN1 and MYOF)
      had recurrent mutations and these mutations were highly correlated with pathway
      deregulation and patient survival. CONCLUSIONS: The recurrent mutations present
      in both DNA and RNA are likely the driver for tumor biology, pathway deregulation
      and clinical outcomes. The information may be used for patient stratification and
      therapeutic target development.

PMID- 24894545
TI  - Examination of ocular biomechanics with a new Scheimpflug technology after
      corneal refractive surgery.
AB  - PURPOSE: To analyze the early results of a new device measuring ocular
      biomechanics after corneal refractive surgery. PATIENTS AND METHODS: Thirty nine
      refractive surgery patients were enrolled in the study (age: 32.6+/-9.9 years).
      Laser in situ keratomileusis (LASIK) was performed on 52 eyes of 26 patients and
      photorefractive keratectomy (PRK) was done on 26 eyes of 13 patients. Ten device
      specific biomechanical parameters, intraocular pressure (IOP) and pachymetry were
      measured preoperatively and at day 1, week 1 and month 1 after the surgeries with
      a new technology based on Scheimpflug imaging (CorVis ST, Oculus). RESULTS: In
      case of LASIK, the day after the procedure, radius values showed significant
      differences compared to preoperative data. One month after surgery, radius
      values, velocity of the second applanation and pachymetry showed significant
      differences compared to preoperative data. In case of PRK, the day after the
      procedure, significant differences in IOP, maximum amplitude at the apex, A1
      time, A2 velocity and highest concavity time were measured. After 1 month of PRK,
      there were no differences in the parameters compared to preoperative data except
      pachymetry. CONCLUSIONS: We observed that some specific biomechanical parameters
      changed measured with CorVis ST after LASIK and PRK, in the early postoperative
      time. However, most of these parameters remain unchanged after one month of LASIK
      and PRK compared to preoperative data.

PMID- 24894546
TI  - Comparison of fitting stability of the different soft toric contact lenses.
AB  - PURPOSE: To compare lens orientation and rotational recovery of five currently
      available soft toric lenses. METHODS: Twenty subjects were recruited and trialed
      with each of the study lenses in a random order. Study lenses were
      PureVision((r)) Toric (B&L), Air Optix((r)) for Astigmatism (Alcon),
      Biofinity((r)) Toric (CooperVision), Acuvue((r)) Advance for Astigmatism
      (Vistakon), and Proclear((r)) Toric (CooperVision). Lens orientation in primary
      position to determine the lens rotation form the vertical position and rotational
      recovery to primary gaze orientation following a 45 degrees  manual
      misorientation for the different lenses was compared. RESULTS: The Biofinity
      Toric showed the lowest rotation from the vertical position and the Proclear
      Toric the highest. Also, the highest and the lowest reorientation speed were
      related to the Biofinity Toric and the Acuvue Advance for Astigmatism,
      respectively. The Repeated Measures ANOVA showed a significant difference in the
      lens rotation (P=0.004) and rotational recovery (P<0.001) among different contact
      lenses and the performed multiple comparisons indicated differences in rotation
      and also in reorientation speed were only seen between the Biofinity Toric when
      compared to four other lenses (P<0.05). CONCLUSION: Although there was
      appropriate fitting, based upon lens orientation and reorientation speed, with
      each of the study lenses it would appear that the optimized ballast technique
      used in the design of the Biofinity Toric helps reduce lens rotation and improve
      rotational recovery compared to others.

PMID- 24894547
TI  - Clinical characteristics of relapses and re-infections in Clostridium difficile
      infection.
AB  - The purpose of this study was to identify factors associated with relapses or re
      infections in patients with recurring Clostridium difficile infections (CDIs).
      From September 2008 to January 2012, cases with two or more isolates from
      consecutive CDI episodes were included. PCR-ribotyping and multilocus variable
      number tandem-repeat analysis were performed using paired isolates. Among 473
      patients, 68 (14.4%) experienced one to five recurrences. Fifty-one of these with
      two or more isolates from consecutive CDI episodes were included in the study; 25
      (49%) were classified as relapses and 26 (51%) as re-infections. Recurrence
      interval was shorter in the relapse group (26.0 versus 67.5 p 0.001), but more
      patients in the re-infection group were hospitalized during recurrence interval
      (53.8% versus 8.0%, p<0.001). Relapse rates in infections by ribotype 017,
      ribotype 018 and other ribotypes were 63.6%, 63.6% and 22.2%, respectively (p
      0.274, p 0.069, and p 0.005). In multivariate logistic regression, infections by
      ribotypes 017 and 018 were associated with CDI relapse (OR 4.77, 95% CI 1.02
      22.31, p 0.047; OR 11.49, 95% CI 2.07-63.72, p 0.005). Conversely, admission
      during recurrence interval lowered the risk of relapse (OR 0.044, 95% CI 0.006
      0.344, p 0.003). In conclusion, relapse was more likely when infection was caused
      by PCR ribotypes 017 and 018.

PMID- 24894548
TI  - alpha-(-)-bisabolol reduces pro-inflammatory cytokine production and ameliorates
      skin inflammation.
AB  - alpha-(-)-bisabolol is a natural monocyclic sesquiterpene present in the
      essential oil has generated considerable interest in the chemical and
      pharmaceutical industries and currently in use in various formulations, mainly in
      cosmetics. This study was undertaken to evaluate its therapeutic profile against
      skin inflammation using in-vitro, in-vivo and in-silico assays.
      Lipopolysachharide (LPS) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced
      production of proinflammatory cytokines (TNF-alpha and IL-6) in macrophage cells
      as well as in TPA-induced skin inflammation in mice was significantly inhibited
      by alpha-(-)-bisabolol. TPA-induced ear thickness, ear weight and lipid
      peroxidation and histopathological damage in the ear tissue were also
      significantly inhibited by topical application of alpha-(-)-bisabolol in a dose
      dependent manner. In-vitro and in-vivo toxicity profiles indicate that it is safe
      for topical application on skin. Molecular docking study also revealed its strong
      binding affinity to the active site of the pro-inflammatory proteins. These
      findings suggested that alpha-(-)-bisabolol may be a useful therapeutic candidate
      for the treatment of skin inflammation. 

PMID- 24894549
TI  - Screening of indigenously isolated fungi for lovastatin production and its in
      vivo evaluation.
AB  - Seven indigenously isolated fungal strains (Aspergillus niger, Aspergillus
      flavus, Aspergillus terreus, Penicillium citrinum, Penicillium notatum, Pleurotus
      ostreatus and Trichoderma viradae) were tested for their potential to produce
      cholesterol lowering drug lovastatin by using different agro-industrial wastes
      (Corn cobs, corn stover, banana stalk, wheat straw, wheat bran, bagasse) in
      submerged as well as solid state fermentation. Aspergillus terreus showed maximum
      production of 18.74 mg/100 mL by wheat bran in solid state fermentation. The
      fermentation parameters (pH, temperature, Inoculum size, moisture contents and
      fermentation time) were also optimized for optimum production of lovastatin. It
      was found that Aspergillus terreus could produce 27.14 mg/100 mL lovastatin under
      optimum condition of pH (6), temperature (30 degrees C), Inoculum size (2 mL),
      moisture contents (60%) and fermentation time (120 hrs) in solid state
      fermentation. The optimized lovastatin was extracted from fermented broth and
      orally administered to rats. The hypocholesterolemic effect of fermented
      lovastatin was evaluated on serum ALT, AST, HDL-C, LDL-C, TG and TC level of
      rats. It was concluded from the study, fermented lovastatin effectively lower the
      cholesterol level of rats.

PMID- 24894550
TI  - NAD+ controls neural stem cell fate in the aging brain.

PMID- 24894552
TI  - Tavaborole (AN-2690) for the treatment of onychomycosis of the toenail in adults.
AB  - Onychomycosis is a challenging nail disease that is difficult to treat due to the
      thickness and impermeability of the nail plate. At present, systemic agents are
      the first-line of treatment for this type of infection; however, topical
      treatment is recommended in milder cases (<50% involvement) or when oral
      treatment is contraindicated. Effective topical treatments capable of penetrating
      the nail plate and reaching the site of infection continue to be sought.
      Tavaborole, the first member of a new class of boron-containing antifungals, is a
      lightweight, water-soluble topical nail solution for the treatment of toenail
      onychomycosis. Tavaborole has a unique mechanism of action against fungal
      organisms and retains antifungal properties in the presence of keratin.
      Tavaborole 5.0% nail solution has shown a favourable safety and efficacy profile
      in Phase II/III clinical trials and is currently under review for licensing in
      the US by the US Food and Drug Administration. 

PMID- 24894551
TI  - Paternal RNA contributions in the Caenorhabditis elegans zygote.
AB  - Development of the early embryo is thought to be mainly driven by maternal gene
      products and post-transcriptional gene regulation. Here, we used metabolic
      labeling to show that RNA can be transferred by sperm into the oocyte upon
      fertilization. To identify genes with paternal expression in the embryo, we
      performed crosses of males and females from divergent Caenorhabditis elegans
      strains. RNA sequencing of mRNAs and small RNAs in the 1-cell hybrid embryo
      revealed that about one hundred sixty paternal mRNAs are reproducibly expressed
      in the embryo and that about half of all assayed endogenous siRNAs and piRNAs are
      also of paternal origin. Together, our results suggest an unexplored paternal
      contribution to early development. 

PMID- 24894554
TI  - Uranyl-oxo coordination directed by non-covalent interactions.
AB  - Directed coordination of weakly Lewis acidic K(+) ions to weakly Lewis basic
      uranyl oxo ligands is accomplished through non-covalent cation-pi and cation-F
      interactions for the first time. Comparison of a family of structurally related
      diarylamide ligands highlights the role that the cation-pi and cation-F
      interactions play in guiding coordination. Cation binding to uranyl is
      demonstrated in the solid state and in solution, providing the shortest reported
      crystallographic uranyl-oxo to potassium distance. UV-Vis, TD-DFT calculations,
      and electrochemical measurements show that cation coordination directly impacts
      the electronics at the uranium(vi) cation. 

PMID- 24894553
TI  - [Melolabial subcutaneous nodule].

PMID- 24894555
TI  - Spontaneous brain parenchymal hemorrhage: an approach to imaging for the
      emergency room radiologist.
AB  - Spontaneous intracranial hemorrhage is a neurological emergency commonly
      encountered by the emergency radiologist. This article reviews the approach to
      spontaneous brain parenchymal hemorrhage, including common causes and the role of
      various neuroimaging modalities in the diagnostic workup. We emphasize the need
      for a primary survey directed at conveying information needed for emergent
      clinical management of the patient and a secondary survey directed at identifying
      the etiology of the hemorrhage. 

PMID- 24894556
TI  - Chemical constituents from Eucalyptus citriodora Hook leaves and their glucose
      transporter 4 translocation activities.
AB  - Bioassay-guided phytochemical investigation of the EtOAc fraction from the leaves
      of a Chinese medicinal herb, Eucalyptus citriodora Hook, resulted in the
      isolation of a new compound rhodomyrtosone E (1), along with 12 known compounds
      (2-13). The structure of the new compound was established by 1D and 2D NMR, MS
      data and X-ray crystallographic analysis. Betulinic acid (2) and corosolic acid
      (5) increased glucose transporter 4 (GLUT-4) translocation by 2.38 and 1.78-fold,
      respectively. 

PMID- 24894557
TI  - Synthesis and antiangiogenic activity of 6-amido-2,4,5-trimethylpyridin-3-ols.
AB  - We recently reported that 6-aminoalkyl-2,4,5-trimethylpyridin-3-ols, novel series
      of 6-aminopyridin-3-ol-based antioxidants, have high antiangiogenic activities.
      In pursuit of wider variety in the analogues, we here report the synthesis and
      antiangiogenic activities of 6-amidoalkyl-2,4,5-trimethylpyridin-3-ols, which
      would not be considered excellent antioxidants because of the poorer electron
      donating effect of the C(6)-amido group than the corresponding C(6)-amino group.
      The selected 6-amido compounds showed up to several fold-higher antiangiogenic
      activities and up to an order of magnitude better antitumor activities in the
      chick embryo chorioallantoic membrane (CAM) assay than SU4312, a positive
      control. We also found that paracetamol, as a direct phenolic analogue of our
      simplest 6-amidopyridin-3-ol, showed a moderate level of antiangiogenic activity.
      We propose this study will offer a basis for a scaffold of novel angiogenesis
      inhibitors that can perturb angiogenesis-related pathologies. 

PMID- 24894558
TI  - Synthesis, antimicrobial and molecular docking studies of enantiomerically pure N
      alkylated beta-amino alcohols from phenylpropanolamines.
AB  - Enantiomerically pure N-alkylated beta-amino alcohols 1a, 1a', 1c, 1c', 1d, 1d',
      1e and 1e', with ee 100% have been synthesized from phenylpropanolamines 2.
      Effect of the neighboring chiral environment on the newly formed chiral center
      has been studied experimentally and concluded that the newly formed chiral
      center's absolute configuration is opposite to the adjacent (alpha- or beta-)
      chiral environment. The antimicrobial activity of the synthesized beta-amino
      alcohols were screened using in vitro disc diffusion method and variable
      antimicrobial activities were shown for 1a, 1a', 1c, 1c', 1d, 1d', 1e &1e' and
      amongst them 1d &1d' exhibited significant activity against bacteria and fungi.
      In silico studies revealed all the synthesized beta-amino alcohols 1a-e and 1a'
      e' have shown good binding energies ranging from -7.38 to -6.09 kJ/mol towards
      the target receptor DNA topoisomerase IV and 1d' has shown maximum binding energy
      -7.38 kJ/mol.

PMID- 24894559
TI  - Synthesis of two new hydroxylated derivatives of spironolactone by microbial
      transformation.
AB  - Spironolactone is a medicinally important molecule that is clinically used in the
      treatment and management of many diseases such as oedema and ascites in cirrhosis
      of the liver, malignant ascites, nephrotic syndrome, chronic lung disease,
      resistant hypertension, congestive heart failure, and primary hyperaldosteronism.
      Microbial transformations of spironolactone by Cunninghamella elegans ATCC 9245
      was carried out. Two new hydroxylated derivatives, 12beta-hydroxy-spironolactone
      and 2alpha-hydroxy-spironolactone, were synthesized. Their structures were
      characterized on the basis of the spectroscopic data. The substrate can be
      efficiently converted into the products within 72 h after its addition to the
      fermentation broth of C. elegans ATCC 9245.

PMID- 24894560
TI  - Discovery of novel 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide
      derivatives as HIF prolyl 4-hydroxylase inhibitors; SAR, synthesis and modeling
      evaluation.
AB  - The design, synthesis, and capacity to inhibit HIF prolyl 4-hydroxylases (PHDs)
      are described for 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide analogs.
      These analogs revealed two kinds of novel scaffolds as PHD2 inhibitors. Synthetic
      routes were developed for the preparation of their analogs containing the new
      scaffolds. In addition, the structure-activity relationship (SAR) of the 2-[2-(3
      hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide derivatives and their biological
      activities were reported. The complex structure of compound 18 with PHD2 was also
      obtained for the purpose of more efficient lead optimization. 

PMID- 24894561
TI  - Synthesis of new verapamil analogues and their evaluation in combination with
      rifampicin against Mycobacterium tuberculosis and molecular docking studies in
      the binding site of efflux protein Rv1258c.
AB  - New verapamil analogues were synthesized and their inhibitory activities against
      Mycobacterium tuberculosis H37Rv determined in vitro alone and in combination
      with rifampicin (RIF). Some analogues showed comparable activity to verapamil and
      exhibited better synergies with RIF. Molecular docking studies of the binding
      sites of Rv1258c, a M. tuberculosis efflux protein previously implicated in
      intrinsic resistance to RIF, suggested a potential rationale for the superior
      synergistic interactions observed with some analogues. 

PMID- 24894562
TI  - Correction of lysosomal dysfunction as a therapeutic strategy for
      neurodegenerative diseases.
AB  - Mutations in the gene that encodes the lysosomal enzyme acid beta-glucosidase
      lead to reduced cellular activity and accumulation of glycosphingolipid
      substrates, biochemical hallmarks of the lysosomal storage disorder Gaucher
      disease (GD). Recently such mutations have been identified as risk factors for
      Parkinson's disease (PD) and related disorders. Both gain-of-function (due to
      toxic cellular accumulation of mutant enzyme) and loss-of-function (due to
      accumulation of lipid substrates) hypotheses have been put forth to address the
      biochemical link between GD and PD. Similarly, links between Alzheimer's disease
      and other lysosomal enzyme deficiencies have begun to emerge. The use of
      pharmacological chaperones to restore the cellular trafficking and activity of
      mutant lysosomal enzymes may offer a novel approach to treat these debilitating
      neurodegenerative diseases. 

PMID- 24894563
TI  - Two-photon in vivo imaging of dendritic spines in the mouse cortex using a
      thinned-skull preparation.
AB  - In the mammalian cortex, neurons form extremely complicated networks and exchange
      information at synapses. Changes in synaptic strength, as well as
      addition/removal of synapses, occur in an experience-dependent manner, providing
      the structural foundation of neuronal plasticity. As postsynaptic components of
      the most excitatory synapses in the cortex, dendritic spines are considered to be
      a good proxy of synapses. Taking advantages of mouse genetics and fluorescent
      labeling techniques, individual neurons and their synaptic structures can be
      labeled in the intact brain. Here we introduce a transcranial imaging protocol
      using two-photon laser scanning microscopy to follow fluorescently labeled
      postsynaptic dendritic spines over time in vivo. This protocol utilizes a thinned
      skull preparation, which keeps the skull intact and avoids inflammatory effects
      caused by exposure of the meninges and the cortex. Therefore, images can be
      acquired immediately after surgery is performed. The experimental procedure can
      be performed repetitively over various time intervals ranging from hours to
      years. The application of this preparation can also be expanded to investigate
      different cortical regions and layers, as well as other cell types, under
      physiological and pathological conditions. 

PMID- 24894565
TI  - Nicotine vaccination--does it have a future?

PMID- 24894564
TI  - Small-for-size syndrome in living-donor liver transplantation using a left lobe
      graft.
AB  - In living-donor liver transplantation with a left lobe graft, which can reduce
      the burden on the donor compared to right lobe graft, the main problem is small
      for-size (SFS) syndrome. SFS syndrome is a multifactorial disease that includes
      aspects related to the graft size, graft quality, recipient factors and even
      technical issues. The main pathophysiology of SFS syndrome is the sinusoidal
      microcirculatory disturbance induced by shear stress, which is caused by
      excessive portal inflow into the smaller graft. The donor age, the presence of
      steatosis of the graft and a poor recipient status are all risk factors for SFS
      syndrome. To resolve SFS syndrome, portal inflow modulation, splenectomy, splenic
      artery modulation and outflow modulation have been developed. It is important to
      establish strict criteria for managing SFS syndrome. Using pharmacological
      interventions and/or therapeutic approaches that promote liver regeneration could
      increase the adequate outcomes in SFS liver transplantation. Left lobe liver
      transplantation could be adopted in Western countries to help resolve the organ
      shortage. 

PMID- 24894566
TI  - Advance distribution of misoprostol for prevention of postpartum hemorrhage (PPH)
      at home births in two districts of Liberia.
AB  - BACKGROUND: A postpartum hemorrhage prevention program to increase uterotonic
      coverage for home and facility births was introduced in two districts of Liberia.
      Advance distribution of misoprostol was offered during antenatal care (ANC) and
      home visits. Feasibility, acceptability, effectiveness of distribution mechanisms
      and uterotonic coverage were evaluated. METHODS: Eight facilities were
      strengthened to provide PPH prevention with oxytocin, PPH management and advance
      distribution of misoprostol during ANC. Trained traditional midwives (TTMs) as
      volunteer community health workers (CHWs) provided education to pregnant women,
      and district reproductive health supervisors (DRHSs) distributed misoprostol
      during home visits. Data were collected through facility and DRHS registers.
      Postpartum interviews were conducted with a sample of 550 women who received
      advance distribution of misoprostol on place of delivery, knowledge, misoprostol
      use, and satisfaction. RESULTS: There were 1826 estimated deliveries during the
      seven-month implementation period. A total of 980 women (53.7%) were enrolled and
      provided misoprostol, primarily through ANC (78.2%). Uterotonic coverage rate of
      all deliveries was 53.5%, based on 97.7% oxytocin use at recorded facility
      vaginal births and 24.9% misoprostol use at home births. Among 550 women
      interviewed postpartum, 87.7% of those who received misoprostol and had a home
      birth took the drug. Sixty-three percent (63.0%) took it at the correct time, and
      54.0% experienced at least one minor side effect. No serious adverse events
      reported among enrolled women. Facility-based deliveries appeared to increase
      during the program. CONCLUSIONS: The program was moderately effective at
      achieving high uterotonic coverage of all births. Coverage of home births was low
      despite the use of two channels of advance distribution of misoprostol. Although
      ANC reached a greater proportion of women in late pregnancy than home visits,
      46.3% of expected deliveries did not receive education or advance distribution of
      misoprostol. A revised community-based strategy is needed to increase advance
      distribution rates and misoprostol coverage rates for home births. Misoprostol
      for PPH prevention appears acceptable to women in Liberia. Correct timing of
      misoprostol self-administration needs improved emphasis during counseling and
      education.

PMID- 24894567
TI  - Development of an improved reverse-phase high-performance liquid chromatography
      method for the simultaneous analyses of trans-/cis-resveratrol, quercetin, and
      emodin in commercial resveratrol supplements.
AB  - The objectives of the study were to develop a reverse-phase high-performance
      liquid chromatography method for the simultaneous analyses of trans-/cis
      resveratrol, emodin, and quercetin and to determine the concentrations of these
      polyphenols in 28 resveratrol supplements. Samples were separated within 15 min
      in a C18 reversed-phase column using mobile phases containing 0.1% formic acid
      and methanol/0.1% formic acid. The calibration graphs for all four compounds were
      linear from 0.1 to 410 MUg/mL (r2=0.99). The concentration of resveratrol as
      stated on the labels was often different from the analytical results, with 21 and
      11% of the total supplements having low or high values, respectively. Many of the
      supplements also contained variable but generally low levels of emodin, a
      compound known to cause diarrhea. The proposed method is a rapid, sensitive,
      accurate, and cost-effective procedure that can be used for the simultaneous
      quantification of four polyphenols in resveratrol supplements.

PMID- 24894569
TI  - The influence of different processing stages on particle size, microstructure,
      and appearance of dark chocolate.
AB  - The effect of different process stages on microstructural and visual properties
      of dark chocolate was studied. Samples were obtained at each phase of the
      manufacture process: mixing, prerefining, refining, conching, and tempering. A
      laser light diffraction technique and environmental scanning electron microscopy
      (ESEM) were used to study the particle size distribution (PSD) and to analyze
      modifications in the network structure. Moreover, colorimetric analyses (L*, h
      degrees , and C*) were performed on all samples. Each stage influenced in
      stronger way the microstructural characteristic of products and above all the
      PSD. Sauter diameter (D [3.2]) decreased from 5.44 MUm of mixed chocolate sample
      to 3.83 MUm, of the refined one. ESEM analysis also revealed wide variations in
      the network structure of samples during the process, with an increase of the
      aggregation and contact point between particles from mixing to refining stage.
      Samples obtained from the conching and tempering were characterized by small PS,
      and a less dense aggregate structure. From color results, samples with the finest
      particles, having larger specific surface area and the smallest diameter,
      appeared lighter and more saturated than those with coarse particles. PRACTICAL
      APPLICATION: Final quality of food dispersions is affected by network and
      particles characteristics. The deep knowledge of the influence of single
      processing stage on chocolate microstructural properties is useful in order to
      improve or modify final product characteristics. ESEM and laser diffraction are
      suitable techniques to study changes in chocolate microstructure.

PMID- 24894568
TI  - Cathepsin K-mediated Notch1 activation contributes to neovascularization in
      response to hypoxia.
AB  - Cysteine proteases play important roles in pathobiology. Here we reveal that
      cathepsin K (CatK) has a role in ischaemia-induced neovascularization. Femoral
      artery ligation-induced ischaemia in mice increases CatK expression and activity,
      and CatK-deficient mice show impaired functional recovery following hindlimb
      ischaemia. CatK deficiency reduces the levels of cleaved Notch1 (c-Notch1), Hes1
      Hey1, Hey2, vascular endothelial growth factor, Flt-1 and phospho-Akt proteins of
      the ischaemic muscles. In endothelial cells, silencing of CatK mimicked, whereas
      CatK overexpression enhanced, the levels of c-Notch1 and the expression of Notch
      downstream signalling molecules, suggesting CatK contributes to Notch1 processing
      and activates downstream signalling. Moreover, CatK knockdown leads to defective
      endothelial cell invasion, proliferation and tube formation, and CatK deficiency
      is associated with decreased circulating endothelial progenitor cells-like
      CD31(+)/c-Kit(+) cells in mice following hindlimb ischaemia. Transplantation of
      bone marrow-derived mononuclear cells from CatK(+/+) mice restores the impairment
      of neovascularization in CatK(-/-) mice. We conclude that CatK may be a potential
      therapeutic target for ischaemic disease. 

PMID- 24894571
TI  - Detoxification of Implant Surfaces Affected by Peri-Implant Disease: An Overview
      of Non-surgical Methods.
AB  - OBJECTIVE: The aim of this review is to summarize the findings of studies that
      have evaluated non-surgical approaches for detoxification of implant body
      surfaces in vitro and in vivo, and to evaluate clinical trials on the use of
      these methodologies for treating peri-implant disease. MATERIALS AND METHODS: A
      literature search was conducted using MEDLINE (Pubmed) from 1966 to 2013. In
      vitro and in vivo studies as well as clinical trials on non-surgical therapy were
      evaluated. The outcome variables were the ability of the therapeutic method to
      eliminate the biofilm and endotoxins from the implant surface, the changes in
      clinical parameters including probing depth, clinical attachment levels, bleeding
      on probing; radiographic bone fill and histological re-osseointegration. RESULTS:
      From 134 articles found 35 were analyzed. The findings, advantages and
      disadvantages of using lasers as well as mechanical and chemical methods are
      discussed. Most of the in vivo and human studies used combination therapies which
      makes determining the efficacy of one specific method difficult. Most human
      studies are case series with short term longitudinal analysis without survival or
      failure reports. CONCLUSION: Complete elimination of the biofilms is difficult to
      achieve using these approaches. All therapies induce changes of the chemical and
      physical properties of the implant surface. Re-osseointegration may be difficult
      to achieve if not impossible without surgical access to ensure thorough
      debridement of the defect and detoxification of the implant surface. Combination
      protocols for non-surgical treatment of peri-implantitis in humans have shown
      some positive clinical results but long-term evaluation to evaluate the validity
      and reliability of the techniques is needed.

PMID- 24894573
TI  - A new quantitative screening method for removable prosthesis using pressure
      indicating paste.
AB  - Aim of this study was to quantitatively evaluate the adaptation of the denture
      base to the mucosa using a non-setting pressure-indicating paste and to examine
      the relationship between quality of fit and the need for denture relining. A
      total of 123 dentures from 70 partially edentulous patients were studied.
      Examination paste extruded from the tip of the 18-G needle was applied to those
      denture surfaces contacting the alveolar crest. The denture was manually
      positioned with all clasps engaged on abutment teeth, and adaptation was assessed
      through paste distribution. Multiple logistic regression was used to analyse
      variables associated with diagnosing the need for a denture reline, producing
      odds ratios and 95% confidence intervals. The spread width was inversely
      proportional to the gap between the denture and mucosa. Regression analysis
      revealed statistically significant associations between the need for a denture
      reline and both the paste spread width and the duration of denture use. According
      to ROC curve analysis of the 'reline' and 'non-reline' groups, the need for a
      denture reline was indicated at a paste spread width of 2.0 mm or less. At this
      2.0-mm threshold, the sensitivity was 85.1% and the specificity was 75.0%. The
      fit of removable denture bases was quantitatively evaluated by measuring the
      spread width of non-setting pressure-indicating paste extruded onto denture fit
      surfaces. The results suggest that the paste spread width is a useful parameter
      for discriminating the need for a denture reline. 

PMID- 24894572
TI  - Associations between neighbourhood environmental characteristics and obesity and
      related behaviours among adult New Zealanders.
AB  - BACKGROUND: The prevalence of adult obesity is escalating in most wealthy and
      middle income countries. Due to the magnitude of this issue, research and
      interventions at the individual-level abound. However, the limited success and
      high costs of such interventions has led to a growing recognition of the
      potential role of environmental factors in reducing obesity and promoting
      physical activity and healthy diets. METHODS: This study utilised individual
      level data from the 2006/7 New Zealand Health Survey on obesity, physical
      activity, diet and socio-economic variables linked to geographic information from
      other sources on potentially aetiologically-relevant environmental factors, based
      on the respondent's residential address. We fitted logistic regression models for
      eight binary measures of weight or weight-related behaviours: 1) overweight; 2)
      obesity; 3) overweight + obesity; 4) active at least 30 minutes a day for 5+ days
      per week; 5) active <30 minutes per week; 6) walk 150 minutes + per week; 7) walk
      <30 minutes per week; and 8) consumption of 5+ fruits and vegetables per day. We
      included a range of independent environmental characteristics of interest in
      separate models. RESULTS: We found that increased neighbourhood deprivation and
      decreased access to neighbourhood greenspace were both significantly associated
      with increased odds of overweight and/or obesity. The results for weight-related
      behaviours indicate that meeting the recommended level of physical activity per
      week was associated with urban/rural status, with higher activity in the more
      rural areas and a surprising tendency for less activity among those living in
      areas with higher levels of active travel to work. Increased access to greenspace
      was associated with high levels of walking, while decreased access to greenspace
      was associated with low levels of walking. There was also a significant trend for
      low levels of walking to be positively associated with neighbourhood deprivation.
      Results for adequate fruit and vegetable consumption show a significant
      urban/rural gradient, with more people meeting recommended levels in the more
      rural compared to more urban areas. CONCLUSION: Similar to findings from other
      international studies, these results highlight greenspace as an amenable
      environmental factor associated with obesity/overweight and also indicate the
      potential benefit of targeted health promotion in both urban and deprived areas
      in New Zealand.

PMID- 24894574
TI  - Reproducibility of aortic intima-media thickness in infants using edge-detection
      software and manual caliper measurements.
AB  - BACKGROUND: Aortic intima-media thickness measured by transabdominal ultrasound
      (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1)
      investigate the reproducibility of aIMT in a population-derived cohort of
      infants; (2) establish the distribution of aIMT in early infancy; (3) compare
      measurement by edge-detection software to that by manual sonographic calipers;
      and (4) assess the effect of individual and environmental variables on image
      quality. METHODS: Participants were term infants recruited to a population
      derived birth cohort study. Transabdominal ultrasound was performed at six weeks
      of age by one of two trained operators. Thirty participants had ultrasounds
      performed by both operators on the same day. Data were collected on environmental
      (infant sleeping, presence of a sibling, use of sucrose, timing during study
      visit) and individual (post-conception age, weight, gender) variables. Two
      readers assessed image quality and measured aIMT by edge-detection software and a
      subset by manual sonographic calipers. Measurements were repeated by the same
      reader and between readers to obtain intra-observer and inter-observer
      reliability. RESULTS: Aortic IMT was measured successfully using edge-detection
      in 814 infants, and 290 of these infants also had aIMT measured using manual
      sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was
      0.90 (95% CI 0.76, 0.96), mean difference 1.5 MUm (95% LOA -39, 59). The between
      reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean
      difference 2 MUm (95% LOA -45.0, 49.0) and with manual caliper measurement (n =
      290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 MUm (95% LOA -51.8,
      61.8). Edge-detection measurements were greater than those from manual
      sonographic calipers (mean aIMT 618 MUm (50) versus mean aIMT 563 MUm (49)
      respectively; p < 0.001, mean difference 44 MUm, 95% LOA -54, 142). With the
      exception of infant crying (p = 0.001), no associations were observed between
      individual and environmental variables and image quality. CONCLUSION: In a
      population-derived cohort of term infants, aIMT measurement has a high level of
      intra and inter-reader reproducibility. Measurement of aIMT using edge-detection
      software gives higher inter-reader ICC than manual sonographic calipers. Image
      quality is not substantially affected by individual and environmental factors.

PMID- 24894575
TI  - Women's social communication about IUDs: a qualitative analysis.
AB  - CONTEXT: Few U.S. women use an IUD, despite the method's efficacy and ease of
      use. While studies have found that misconceptions about IUDs are prevalent, few
      have examined the influence of women's social networks on perceptions of the
      method. METHODS: Twenty-four interviews and three focus groups (comprising 14
      participants) were conducted in 2013 with a diverse sample of women aged 15-45
      recruited from family planning clinics and the community in San Francisco. Half
      of participants had used IUDs. Women were asked about their social communication
      concerning contraceptives, particularly IUDs, and about the content of the
      information they had received or given. Transcripts were analyzed using a
      modified grounded theory approach to identify themes of interest. RESULTS: Women
      reported that communication with female friends and family members was a valued
      means of obtaining information about contraceptives, and that negative
      information (which often was incorrect) was more prevalent and memorable than
      positive information in such communication. Women heard about negative
      experiences with IUDs from social contacts and television commercials; clinicians
      were a major source of positive information. Women who had never used IUDs
      expressed interest in learning about potential side effects and how IUDs feel,
      while users reported emphasizing to friends and family the method's efficacy and
      ease of use. CONCLUSIONS: Misinformation and negative information about IUDs are
      prevalent in social communication, and the information transmitted through social
      networks differs from the information never-users wish to receive. Findings
      support the creation of peer-led interventions to encourage IUD users to share
      positive personal experiences and evidence-based information.

PMID- 24894576
TI  - Positive end-expiratory pressure in surgery: good or bad?

PMID- 24894578
TI  - Idiopathic intracranial hypertension: new insights, new definitions but the same
      old problems.

PMID- 24894579
TI  - Physical activity on endothelial and erectile dysfunction: a literature review.
AB  - Physical inactivity, diabetes, hypertension, dyslipidemia, smoking and obesity
      were associated with imbalance in oxidative stress, leading to endothelial
      dysfunction. Such dysfunction is present in both cardiovascular disease (CVD) and
      erectile dysfunction (ED). ED is the persistent inability to achieve or sustain
      an erection sufficient for satisfactory sexual performance and is one of the
      first manifestations of endothelial damage in men with CVD risk factors. The
      purpose of this article is to review the results of studies involving physical
      activity, CVD, endothelial dysfunction and ED in order to verify its
      applicability for improving the health and quality of life of men with such
      disorders. There is consistent evidence that endothelial damage is intimately
      linked to ED, and this manifestation seems to be associated with the appearance
      CVDs. On the other hand, physical activity has been pointed out as an important
      clinical strategy in the prevention and treatment of CVDs and ED mainly
      associated with improvement of endothelial function. However, further
      experimental and clinical prospective investigations are needed to test the role
      of physical exercises in the modulation of endothelial function and their
      implications on erectile function and the appearance of CVDs.

PMID- 24894577
TI  - High versus low positive end-expiratory pressure during general anaesthesia for
      open abdominal surgery (PROVHILO trial): a multicentre randomised controlled
      trial.
AB  - BACKGROUND: The role of positive end-expiratory pressure in mechanical
      ventilation during general anaesthesia for surgery remains uncertain. Levels of
      pressure higher than 0 cm H2O might protect against postoperative pulmonary
      complications but could also cause intraoperative circulatory depression and lung
      injury from overdistension. We tested the hypothesis that a high level of
      positive end-expiratory pressure with recruitment manoeuvres protects against
      postoperative pulmonary complications in patients at risk of complications who
      are receiving mechanical ventilation with low tidal volumes during general
      anaesthesia for open abdominal surgery. METHODS: In this randomised controlled
      trial at 30 centres in Europe and North and South America, we recruited 900
      patients at risk for postoperative pulmonary complications who were planned for
      open abdominal surgery under general anaesthesia and ventilation at tidal volumes
      of 8 mL/kg. We randomly allocated patients to either a high level of positive end
      expiratory pressure (12 cm H2O) with recruitment manoeuvres (higher PEEP group)
      or a low level of pressure (<=2 cm H2O) without recruitment manoeuvres (lower
      PEEP group). We used a centralised computer-generated randomisation system.
      Patients and outcome assessors were masked to the intervention. Primary endpoint
      was a composite of postoperative pulmonary complications by postoperative day 5.
      Analysis was by intention-to-treat. The study is registered at Controlled
      Trials.com, number ISRCTN70332574. FINDINGS: From February, 2011, to January,
      2013, 447 patients were randomly allocated to the higher PEEP group and 453 to
      the lower PEEP group. Six patients were excluded from the analysis, four because
      they withdrew consent and two for violation of inclusion criteria. Median levels
      of positive end-expiratory pressure were 12 cm H2O (IQR 12-12) in the higher PEEP
      group and 2 cm H2O (0-2) in the lower PEEP group. Postoperative pulmonary
      complications were reported in 174 (40%) of 445 patients in the higher PEEP group
      versus 172 (39%) of 449 patients in the lower PEEP group (relative risk 1.01; 95%
      CI 0.86-1.20; p=0.86). Compared with patients in the lower PEEP group, those in
      the higher PEEP group developed intraoperative hypotension and needed more
      vasoactive drugs. INTERPRETATION: A strategy with a high level of positive end
      expiratory pressure and recruitment manoeuvres during open abdominal surgery does
      not protect against postoperative pulmonary complications. An intraoperative
      protective ventilation strategy should include a low tidal volume and low
      positive end-expiratory pressure, without recruitment manoeuvres. FUNDING:
      Academic Medical Center (Amsterdam, Netherlands), European Society of
      Anaesthesiology.

PMID- 24894580
TI  - Estimating ON and OFF contributions to the photopic hill: normative data and
      clinical applications.
AB  - BACKGROUND: With progressively brighter stimuli, the amplitude of the b-wave of
      the human photopic electroretinogram (ERG) first increases to a maximal value
      (Vmax) and then decreases to finally reach a plateau, a phenomenon known as the
      photopic hill (PH). A mathematical model combining a Gaussian (G) and a logistic
      (L) growth function was previously proposed to fit this unusual luminance
      response curve, where the G and L functions were suggested to represent,
      respectively, the OFF and ON retinal pathway contributions to the building of the
      PH. METHOD: The PHs of patients presenting stationary diseases affecting
      specifically the ON (3 CSNB-1) or OFF (4 CPCPA) retinal pathways as well as
      patients affected with retinitis pigmentosa (14 RP) of different stages or
      etiology were analyzed using this mathematical model and compared to the PHs of a
      group of 28 normal subjects. RESULTS: The PH of the CSNB-1 patients had a much
      larger contribution from the G function compared to normal subjects, whereas the
      opposite was observed for the CPCPA patients. On the other hand, analysis of data
      from RP patients revealed variable G-L contributions to the building of their PH.
      CONCLUSION: In this study, we confirm the previous claim that the luminance
      response function of the photopic ERG b-wave can be decomposed into a Gaussian
      function and a logistic growth function representing, respectively, the OFF and
      ON retinal pathways. Furthermore, our findings suggest that this mathematical
      decomposition could be useful to further segregate and potentially follow the
      progression of retinopathies such as RP.

PMID- 24894582
TI  - Interference of the end: why recency bias in memory determines when a food is
      consumed again.
AB  - The results of three experiments reveal that memory for end enjoyment, rather
      than beginning enjoyment, of a pleasant gustatory experience determines how soon
      people desire to repeat that experience. We found that memory for end moments,
      when people are most satiated, interferes with memory for initial moments.
      Consequently, end moments are more influential than initial moments when people
      decide how long to wait until consuming a food again. The findings elucidate the
      role of memory in delay until repeated consumption, demonstrate how sensory
      specific satiety and portion sizes influence future consumption, and suggest one
      process by which recency effects influence judgments and decisions based on past
      experiences. 

PMID- 24894581
TI  - Empathy and involvement in bullying in children and adolescents: a systematic
      review.
AB  - Based on the premise that bullies are deficient in empathy or even lack it
      completely, bullying prevention and intervention programs often include empathy
      training. These programs are not always as effective as they aim to be, which may
      be caused by a failure to acknowledge the multidimensional nature of empathy as
      well as its complex association with involvement in bullying. To provide a clear
      overview of the research on the association between empathy and involvement in
      bullying, this article systematically reviews 40 studies on the association of
      cognitive empathy (24 studies) and affective empathy (38 studies) with four
      categories of involvement in bullying: bullying, victimization, defending, and
      bystanding. The results showed that bullying was negatively associated with
      cognitive and-in particular-affective empathy. Victimization was negatively
      associated with cognitive empathy but not with affective empathy. Defending was
      consistently positively associated with both types of empathy. Contradictory
      findings were observed in bystanding, with studies reporting both negative and
      positive associations with cognitive empathy, and studies reporting negative and
      no associations with affective empathy. Together, the findings stress the
      importance of the distinction between cognitive and affective empathy in
      involvement in bullying and suggest different intervention strategies for the
      four types of involvement in bullying. 

PMID- 24894583
TI  - Sleep underpins the plasticity of language production.
AB  - The constraints that govern acceptable phoneme combinations in speech perception
      and production have considerable plasticity. We addressed whether sleep
      influences the acquisition of new constraints and their integration into the
      speech-production system. Participants repeated sequences of syllables in which
      two phonemes were artificially restricted to syllable onset or syllable coda,
      depending on the vowel in that sequence. After 48 sequences, participants either
      had a 90-min nap or remained awake. Participants then repeated 96 sequences so
      implicit constraint learning could be examined, and then were tested for
      constraint generalization in a forced-choice task. The sleep group, but not the
      wake group, produced speech errors at test that were consistent with restrictions
      on the placement of phonemes in training. Furthermore, only the sleep group
      generalized their learning to new materials. Polysomnography data showed that
      implicit constraint learning was associated with slow-wave sleep. These results
      show that sleep facilitates the integration of new linguistic knowledge with
      existing production constraints. These data have relevance for systems
      consolidation models of sleep. 

PMID- 24894584
TI  - Sensory systems: Eat well to improve smell?

PMID- 24894586
TI  - Multiple familial pilomatrixomas in three generations: an unusual clinical
      picture.
AB  - Pilomatrixomas are benign cutaneous tumors derived from hair matrix cells of
      unclear etiology. Pilomatrixomas commonly demonstrate somatic mutations in
      CTNNB1, a gene coding beta-catenin, a protein involved with hair follicle
      development. Multiple familial pilomatrixomas rarely occur and are most often
      associated with autosomal dominant conditions such as myotonic dystrophy and
      familial adenomatous polyposis (FAP). Nine families with multiple familial
      pilomatrixomas and no demonstrable underlying association have been reported in
      the literature. We present a tenth family in which five members spanning three
      generations grew multiple pilomatrixomas in the absence of any previously
      reported associations. No evidence of myotonic dystrophy, FAP, or other known
      associations was found. Extreme tiredness, behavioral problems, and sensory
      disturbances were common features across three generations but bore no temporal
      relation to the pilomatrixomas. The existence of a germline mutation in CTNNB1 to
      explain these symptoms has yet to be shown. Pilomatrixomas are potentially
      cutaneous markers of significant underlying pathologies. Patients presenting with
      multiple or familial pilomatrixomas should be thoroughly assessed for other
      pathologies and offered genetic screening to ensure that important diagnoses are
      not overlooked. 

PMID- 24894587
TI  - Change of a motor synergy for dampening hand vibration depending on a task
      difficulty.
AB  - The present study investigated the relationship between the number of usable
      degrees of freedom (DOFs) and joint coordination during a human-dampening hand
      vibration task. Participants stood on a platform generating an anterior-posterior
      directional oscillation and held a water-filled cup. Their usable DOFs were
      changed under the following conditions of limb constraint: (1) no constraint; (2)
      ankle constrained; and (3) ankle-knee constrained. Kinematic whole-body data were
      recorded using a three-dimensional position measurement system. The jerk of each
      body part was evaluated as an index of oscillation intensity. To quantify joint
      coordination, an uncontrolled manifold (UCM) analysis was applied and the
      variance of joints related to hand jerk divided into two components: a UCM
      component that did not affect hand jerk and an orthogonal (ORT) component that
      directly affected hand jerk. The results showed that hand jerk when the task used
      a cup filled with water was significantly smaller than when a cup containing
      stones was used, regardless of limb constraint condition. Thus, participants
      dampened their hand vibration utilizing usable joint DOFs. According to UCM
      analysis, increasing the oscillation velocity and the decrease in usable DOFs by
      the limb constraints led to an increase of total variance of the joints and the
      UCM component, indicating that a synergy-dampening hand vibration was enhanced.
      These results show that the variance of usable joint DOFs is more fitted to the
      UCM subspace when the joints are varied by increasing the velocity and limb
      constraints and suggest that humans adopt enhanced synergies to achieve more
      difficult tasks.

PMID- 24894585
TI  - Muller glial cell reprogramming and retina regeneration.
AB  - Muller glia are the major glial component of the retina. They are one of the last
      retinal cell types to be born during development, and they function to maintain
      retinal homeostasis and integrity. In mammals, Muller glia respond to retinal
      injury in various ways that can be either protective or detrimental to retinal
      function. Although these cells can be coaxed to proliferate and generate neurons
      under special circumstances, these responses are meagre and insufficient for
      repairing a damaged retina. By contrast, in teleost fish (such as zebrafish), the
      response of Muller glia to retinal injury involves a reprogramming event that
      imparts retinal stem cell characteristics and enables them to produce a
      proliferating population of progenitors that can regenerate all major retinal
      cell types and restore vision. Recent studies have revealed several important
      mechanisms underlying Muller glial cell reprogramming and retina regeneration in
      fish that may lead to new strategies for stimulating retina regeneration in
      mammals. 

PMID- 24894588
TI  - Influence of ankle loading on the relationship between temporal pressure and
      motor coordination during a whole-body paired task.
AB  - We investigated whether ankle loading modifies the relationship between temporal
      pressure and motor coordination during a whole-body paired task. Eight young
      healthy adults standing in an erect posture performed multiple series of
      simultaneous rapid leg flexions paired with ipsilateral index finger extensions.
      They repeated the task ten times in three load conditions: unloaded, loaded
      (where additional 5-kg inertia was attached to the ankles), and post-loaded
      (immediately following the loaded condition). These conditions were conducted in
      two blocks of temporal pressure: self-initiated (SI) versus reaction time (RT).
      When participants were unloaded, the results showed that index finger extension
      preceded swing heel-off in RT, and conversely in SI. By contrast, when the
      participants were loaded, swing heel-off preceded index finger extension in both
      SI and RT, showing that loading modified the relationship between temporal
      pressure and movement synchronization in RT only. However, loading did not induce
      any increase in the error of synchronization. Furthermore, in both the unloaded
      and loaded conditions, the duration of "anticipatory postural adjustments" (APA)
      was shorter when the temporal pressure was increased. Interestingly, the shorter
      APA duration was compensated by an increase in APA amplitude. Thus, loading did
      not modify the relationship between temporal pressure and anticipatory postural
      dynamics. Post-loaded and unloaded conditions produced the same results. These
      results show that the central nervous system optimally adapts the relationship
      between temporal pressure and motor coordination to transitory changes in the
      mechanical properties of the lower limbs, here due to ankle loading.

PMID- 24894589
TI  - Impact of visceral fat ratio on sleep-related erection: a retrospective study of
      elderly patients.
AB  - OBJECTIVES: To investigate the impact of visceral fat accumulation on the
      preoperative erectile function of elderly patients undergoing radical
      prostatectomy. METHODS: A total of 83 patients who underwent radical
      prostatectomy from August 2005 through August 2013 were included in the present
      study. Findings at preoperative computed tomography scanning and sleep-related
      erection were used to determine the objective erectile function. Sleep-related
      erection was measured with an erectometer during at least three nights, and we
      assessed the maximum penile circumferential change. The visceral fat ratio was
      calculated as the ratio of the visceral fat area to the total subcutaneous fat
      area on computed tomography images, and the influence of these parameters on
      preoperative erectile function was assessed. RESULTS: In simple linear regression
      analysis there was a strong correlation between the waist circumference and
      visceral fat ratio (P < 0.01). A visceral fat ratio of 55% was equivalent to a
      waist circumference of 85 cm, which is the standard value for central obesity in
      Japan. Furthermore, the factor that most negatively affected maximum penile
      circumferential change was the visceral fat ratio. In addition, only a visceral
      fat ratio of 55% or greater was a significant independent risk factor for
      declining maximum penile circumferential change in both univariate and
      multivariate analyses (P = 0.04 and 0.02, respectively). CONCLUSIONS: The present
      study is the first to show the utility of the visceral fat ratio as an index of
      central obesity and the relationship with sleep-related erection in elderly men.

PMID- 24894590
TI  - Vertebrate paralogous CRMPs in nervous system: evolutionary, structural, and
      functional interplay.
AB  - Collapsin response mediator proteins (CRMPs) family predominantly expressed in
      the developing nervous system as key molecular components in shaping neural
      networks. However, knowledge of the evolution of CRMPs is limited. To gain
      further insight into nervous system evolution in vertebrates, we have performed a
      comprehensive bioinformatics analysis of CRMPs, including phylogenetic analysis,
      an examination of positively selected sites and putative biological significance
      and protein structure analysis. Sequence similarity searches have been performed
      in genome data to identify homologues of CRMPs in vertebrates. Phylogenetic
      relationships were constructed to trace the family evolutionary history. Five
      CRMP members might form through gene duplication. The inferred evolutionary
      transitions that separate members which belong to different gene clusters
      correlated with changes in functional properties. To determine the mode of
      evolution in vertebrates, we used several complementary methods, including site
      specific models, branch-specific models and branch-site models to estimated
      molecular substitution rates and determined the selective force operating at each
      CRMPs gene cluster. Nineteen positive selection sites and the functional areas
      were detected in this process. This research gives us a first look at the
      phylogeny and evolutionary selection pressure of the CRMP family in vertebrates.
      Additionally, we identified a number of critical amino acid residues likely
      relevant for the distinct functional properties of the paralogues. In conclusion,
      the results of this study contribute novel detailed information about the
      molecular evolution of CRMPs, reveal CRMPs' roles in the pathogenesis of nervous
      system diseases and provide a new thought of the targeted therapy from the
      molecular evolution angle. 

PMID- 24894591
TI  - Cloning and characterization of rat Luman/CREB3, a transcription factor highly
      expressed in nervous system tissue.
AB  - Human Luman/CREB3 is a basic leucine zipper transcription factor involved in
      regulation of the unfolded protein response, dendritic cell maturation, and cell
      migration. But despite reported expression in primary sensory neurons, little is
      known about its role in the nervous system. To begin investigations into its role
      in the adult rat nervous system, the rat Luman/CREB3 coding sequence was isolated
      so its expression within the nervous system could be determined. The rat
      Luman/CREB3 clone contains a full-length open reading frame encoding 387 amino
      acids. The recombinant protein generated from this clone activated transcription
      in a manner equivalent to human Luman/CREB3 from a CAT reporter plasmid construct
      containing the unfolded protein response element. Quantitative RT-PCR revealed
      that rat Luman/CREB3 transcripts in a variety of rat tissues with the highest
      levels in nervous system tissue. In situ hybridization performed on tissue
      sections confirmed the findings and demonstrated that the Luman/CREB3 mRNA
      hybridization signal localizes to neurons and satellite glial cells in dorsal
      root ganglia, the cytoplasm of hepatocytes in liver, and the hippocampal
      pyramidal cell layers of CA1 and CA3 and the granular cell layer of the dentate
      gyrus. Collectively, these findings support a role for Luman/CREB3 in the
      regulation of nervous system function. 

PMID- 24894592
TI  - Moving improvement research closer to practice: the Researcher-in-Residence
      model.
AB  - The traditional separation of the producers of research evidence in academia from
      the users of that evidence in healthcare organisations has not succeeded in
      closing the gap between what is known about the organisation and delivery of
      health services and what is actually done in practice. As a consequence, there is
      growing interest in alternative models of knowledge creation and mobilisation,
      ones which emphasise collaboration, active participation of all stakeholders, and
      a commitment to shared learning. Such models have robust historical,
      philosophical and methodological foundations but have not yet been embraced by
      many of the people working in the health sector. This paper presents an emerging
      model of participation, the Researcher-in-Residence. The model positions the
      researcher as a core member of a delivery team, actively negotiating a body of
      expertise which is different from, but complementary to, the expertise of
      managers and clinicians. Three examples of in-residence models are presented: an
      anthropologist working as a member of an executive team, operational researchers
      working in a front-line delivery team, and a Health Services Researcher working
      across an integrated care organisation. Each of these examples illustrates the
      contribution that an embedded researcher can make to a service-based team. They
      also highlight a number of unanswered questions about the model, including the
      required level of experience of the researcher and their areas of expertise, the
      institutional facilitators and barriers to embedding the model, and the risk that
      the independence of an embedded researcher might be compromised. The Researcher
      in-Residence model has the potential to engage both academics and practitioners
      in the promotion of evidence-informed service improvement, but further evaluation
      is required before the model should be routinely used in practice. 

PMID- 24894593
TI  - Radiation dose reduction in cone-beam computed tomography of extremities:
      evaluation of a novel radiation shield.
AB  - Cone-beam computed tomography (CBCT) is a relatively new technique for imaging of
      extremities. It provides high-resolution images with lower effective dose
      compared to conventional CT. However following the ALARA principle, CBCT-imaging
      protocols and practices must also be optimised to minimize the dose absorbed by
      the patient as well as personnel. The aim of this study is to evaluate the effect
      of a novel scanner-attached radiation shield on the dose absorbed by the patient
      and on the amount of scattered radiation around the scanner.An orthopedic CBCT
      scanner was applied for comparing the doses with and without the shield during an
      elbow and a knee scan. A homogeneous 8 cm PMMA phantom with either an
      anthropomorphic Alderson phantom or a 16 cm PMMA phantom simulated the tissues of
      a patient. Measurements were made for several scan parameters using calibrated
      dose meters.The results show that the radiation shield significantly decreased
      the doses measured on the patient during CBCT scans of the elbow and the knee.
      The usage of the shield decreased the absorbed doses by up to 95.5%. Also
      scattered radiation around the gantry decreased notably. The use of the shield is
      highly recommended, especially for pediatric patients. 

PMID- 24894594
TI  - Alveolar and exhaled NO in relation to asthma characteristics--effects of
      correction for axial diffusion.
AB  - BACKGROUND: Inflammation in the small airways might contribute to incomplete
      asthma disease control despite intensive treatment in some subgroups of patients.
      Exhaled NO (FeNO) is a marker of inflammation in asthma and the estimated NO
      contribution from small airways (CalvNO ) is believed to reflect distal
      inflammation. Recent studies recommend adjustments of CalvNO for trumpet model
      and axial diffusion (TMAD-adj). This study aimed to investigate the clinical
      correlates of CalvNO , both TMAD-adjusted and unadjusted. METHODS: Asthma
      symptoms, asthma control, lung function, bronchial responsiveness, blood
      eosinophils, atopy and treatment level were assessed in 410 subjects, aged 10-35
      years. Exhaled NO was measured at different flow-rates and CalvNO calculated,
      with TMAD-adjustment according to Condorelli. RESULTS: Trumpet model and axial
      diffusion-adjusted CalvNO was not related to daytime wheeze (P = 0.27), FEF50 (P
      = 0.23) or bronchial responsiveness (P = 0.52). On the other hand, unadjusted
      CalvNO was increased in subjects with daytime wheeze (P < 0.001), decreased FEF50
      (P = 0.02) and with moderate-to-severe compared to normal bronchial
      responsiveness (P < 0.001). All these characteristics correlated with increased
      FeNO (all P < 0.05). Unadjusted CalvNO was positively related to bronchial NO
      flux (J'awNO ) (r = 0.22, P < 0.001) while TMAD-adjCalvNO was negatively related
      to J'awNO (r = -0.38, P < 0.001). CONCLUSIONS: Adjusted CalvNO was not associated
      with any asthma characteristics studied in this large asthma cohort. However,
      both FeNO and unadjusted CalvNO related to asthma symptoms, lung function and
      bronchial responsiveness. We suggest a potential overadjustment by current TMAD
      corrections, validated in healthy or unobstructed asthmatics. Further studies
      assessing axial diffusion in asthmatics with different degrees of airway
      obstruction and the validity of proposed TMAD-corrections are warranted.

PMID- 24894595
TI  - Novel homozygous SLC29A3 mutations among two unrelated Egyptian families with
      spectral features of H-syndrome.
AB  - OBJECTIVES: H syndrome and pigmented hypertrichosis with insulin-dependent
      diabetes mellitus (PHID) had been described as two autosomal recessive disorders.
      We aim to screen for pathogenic SLC29A3 mutations in two unrelated Egyptian
      families with affected siblings of these overlapping syndromes. METHODS:
      Clinical, laboratory, histopathological, and radiological characteristics of
      individuals probably diagnosed as H and/or PHID syndrome were reported. Mutation
      analysis of SLC29A3 gene was performed for all members of the two Egyptian
      families. RESULTS: All affected individuals were females; proband of family-I
      (A1961) displayed overlapping features of H syndrome and PHID, while her younger
      brother (A1962) was asymptomatic. A1961 presented with previously undescribed
      features; absent pectoralis major muscle and a supracondylar bony spur in left
      humerus. In family-II, probands (A1965 and A1966) had clinical features
      consistent with classical H syndrome with unique early onset of cutaneous
      phenomena at birth. Mutation analysis of SLC29A3 revealed homozygous mutation
      previously reported in literature c.1279G>A [p.G427S] in A1961 and unexpectedly
      in the asymptomatic A1962 of family-I. Probands of family-II were homozygous for
      a novel mutation c.401G>A [p.R134H], in the same codon that was published in an
      Indian boy [p.R134C]. CONCLUSIONS: We emphasize the inter- and intra-familial
      genetic heterogeneity among Egyptian patients with overlapping features of
      SLC29A3 disorders. This suggests the presence of other factors like regulatory
      genes or epigenetic factors that may explain variable disease manifestations and
      severity.

PMID- 24894597
TI  - Observations on the epidemiology of gastrointestinal and liver cancers in the
      Asia-Pacific region.
AB  - Gastric cancer (GC) has long been thought to be an Asian type of cancer that is
      broadly associated with poverty, whereas colorectal cancer (CRC) has been thought
      to be a Western type of cancer associated with affluence. The incidence of GC has
      declined dramatically in the West but has a very high incidence in East Asia. The
      age-standardized incidence rates (ASR) have also declined. The decrease in the
      incidence of GC is associated with the decrease in the prevalence of Helicobacter
      pylori (H. pylori) infection worldwide. The discrepancy between a high H. pylori
      infection rate and a low GC incidence is seen chiefly among southern Asians of
      Indian origin and has been aptly termed the "Indian enigma". CRC is a new
      emerging cancer in this region. Some of the highest CRC ASR have been reported
      from Asian countries, in many of which it has now surpassed that of GC. Liver
      cancer is also an important cancer in the Asia-Pacific region. The highest ASR
      worldwide is reported from the Asian countries of Mongolia, Korea and Japan. The
      predominant underlying etiology across the region has been hepatitis B virus
      infection, except in Japan, where hepatitis C is an important cause of
      hepatocellular carcinoma (HCC). With mass vaccination of hepatitis B at birth and
      improved public health measures in many countries, hepatitis B and C are set to
      decline with time. However, the exponential increase in obesity and consequent
      non-alcoholic fatty liver disease portends a future epidemic of fatty liver
      related HCC. 

PMID- 24894596
TI  - Mortality after total hip replacement surgery: A systematic review.
AB  - Total hip replacement causes a short-term increase in the risk of mortality. It
      is important to quantify this and to identify modifiable risk factors so that the
      risk of post-operative mortality can be minimised. We performed a systematic
      review and critical evaluation of the current literature on the topic. We
      identified 32 studies published over the last 10 years which provide either 30
      day or 90-day mortality data. We estimate the pooled incidence of mortality
      during the first 30 and 90 days following hip replacement to be 0.30% (95% CI
      0.22 to 0.38) and 0.65% (95% CI 0.50 to 0.81), respectively. We found strong
      evidence of a temporal trend towards reducing mortality rates despite
      increasingly co-morbid patients. The risk factors for early mortality most
      commonly identified are increasing age, male gender and co-morbid conditions,
      particularly cardiovascular disease. Cardiovascular complications appear to have
      overtaken fatal pulmonary emboli as the leading cause of death after hip
      replacement. Cite this article: Bone Joint Res 2014;3:175-82. 

PMID- 24894598
TI  - Adult type granulosa cell tumor of the testis with a heterologous sarcomatous
      component: case report and review of the literature.
AB  - Adult testicular granulosa cell tumors are rare sex cord- stromal tumors of which
      only 45 have been previously reported. As compared with their ovarian
      counterparts, these tumors may follow a more aggressive course because the
      proportion of malignant cases is higher. We report here a unique case of a 78
      year Caucasian with a left sided adult type granulosa cell tumor with a
      heterologous sarcomatous tumor component. A heterologous sarcomatous component
      has occasionally been observed in ovarian tumors but never in testicular
      granulosa cell tumors. The sarcomatous component showed a higher number of
      mitotic figures (1/Hpf) and a marked proliferation rate (up to 50% Ki 67 positive
      cells) compared with the granulosa type tumor component. CD 99 and the
      progesterone receptor were positive in both tumor components, inhibin and
      calretinin only in the granulosa cells, and pancytokeratin only in the
      sarcomatouse one. Key words: testis - ovary - granulosa cells - sarcoma - inhibin
      Runing title: testicular sarcomatous granulosa tumor. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/6959043481207016.

PMID- 24894600
TI  - PVT: an efficient computational procedure to speed up next-generation sequence
      analysis.
AB  - BACKGROUND: High-throughput Next-Generation Sequencing (NGS) techniques are
      advancing genomics and molecular biology research. This technology generates
      substantially large data which puts up a major challenge to the scientists for an
      efficient, cost and time effective solution to analyse such data. Further, for
      the different types of NGS data, there are certain common challenging steps
      involved in analysing those data. Spliced alignment is one such fundamental step
      in NGS data analysis which is extremely computational intensive as well as time
      consuming. There exists serious problem even with the most widely used spliced
      alignment tools. TopHat is one such widely used spliced alignment tools which
      although supports multithreading, does not efficiently utilize computational
      resources in terms of CPU utilization and memory. Here we have introduced PVT
      (Pipelined Version of TopHat) where we take up a modular approach by breaking
      TopHat's serial execution into a pipeline of multiple stages, thereby increasing
      the degree of parallelization and computational resource utilization. Thus we
      address the discrepancies in TopHat so as to analyze large NGS data efficiently.
      RESULTS: We analysed the SRA dataset (SRX026839 and SRX026838) consisting of
      single end reads and SRA data SRR1027730 consisting of paired-end reads. We used
      TopHat v2.0.8 to analyse these datasets and noted the CPU usage, memory footprint
      and execution time during spliced alignment. With this basic information, we
      designed PVT, a pipelined version of TopHat that removes the redundant
      computational steps during 'spliced alignment' and breaks the job into a pipeline
      of multiple stages (each comprising of different step(s)) to improve its resource
      utilization, thus reducing the execution time. CONCLUSIONS: PVT provides an
      improvement over TopHat for spliced alignment of NGS data analysis. PVT thus
      resulted in the reduction of the execution time to ~23% for the single end read
      dataset. Further, PVT designed for paired end reads showed an improved
      performance of ~41% over TopHat (for the chosen data) with respect to execution
      time. Moreover we propose PVT-Cloud which implements PVT pipeline in cloud
      computing system.

PMID- 24894599
TI  - Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and
      ADP.
AB  - Schistosomes are parasitic worms that can live in the bloodstream of their
      vertebrate hosts for many years. It has been proposed that the worms impinge on
      host purinergic signalling by degrading proinflammatory molecules like ATP as
      well as prothrombotic mediators like ADP. This capability may help explain the
      apparent refractoriness of the worms to both immune elimination and thrombus
      formation. Three distinct ectoenzymes, expressed at the host-exposed surface of
      the worm's tegument, are proposed to be involved in the catabolism of ATP and
      ADP. These are alkaline phosphatase (SmAP), phosphodiesterase (SmNPP-5), and ATP
      diphosphohydrolase (SmATPDase1). It has recently been shown that only one of
      these enzymes-SmATPDase1-actually degrades exogenous ATP and ADP. However, a
      second ATP diphosphohydrolase homolog (SmATPDase2) is located in the tegument and
      has been reported to be released by the worms. It is possible that this enzyme
      too participates in the cleavage of exogenous nucleotide tri- and di-phosphates.
      To test this hypothesis, we employed RNA interference (RNAi) to suppress the
      expression of the schistosome SmATPDase1 and SmATPDase2 genes. We find that only
      SmATPDase1-suppressed parasites are significantly impaired in their ability to
      degrade exogenously added ATP or ADP. Suppression of SmATPDase2 does not
      appreciably affect the worms' ability to catabolize ATP or ADP. Furthermore, we
      detect no evidence for the secretion or release of an ATP-hydrolyzing activity by
      cultured parasites. The results confirm the role of tegumental SmATPDase1, but
      not SmADTPDase2, in the degradation of the exogenous proinflammatory and
      prothrombotic nucleotides ATP and ADP by live intravascular stages of the
      parasite. 

PMID- 24894601
TI  - A strategy for sensitive, large scale quantitative metabolomics.
AB  - Metabolite profiling has been a valuable asset in the study of metabolism in
      health and disease. However, current platforms have different limiting factors,
      such as labor intensive sample preparations, low detection limits, slow scan
      speeds, intensive method optimization for each metabolite, and the inability to
      measure both positively and negatively charged ions in single experiments.
      Therefore, a novel metabolomics protocol could advance metabolomics studies.
      Amide-based hydrophilic chromatography enables polar metabolite analysis without
      any chemical derivatization. High resolution MS using the Q-Exactive (QE-MS) has
      improved ion optics, increased scan speeds (256 msec at resolution 70,000), and
      has the capability of carrying out positive/negative switching. Using a cold
      methanol extraction strategy, and coupling an amide column with QE-MS enables
      robust detection of 168 targeted polar metabolites and thousands of additional
      features simultaneously.  Data processing is carried out with commercially
      available software in a highly efficient way, and unknown features extracted from
      the mass spectra can be queried in databases. 

PMID- 24894603
TI  - Comparison of the QIAGEN artus HCV QS-RGQ test with the Roche COBAS
      Ampliprep/COBAS TaqMan HCV test v2.0 for the quantification of HCV-RNA in plasma
      samples.
AB  - BACKGROUND: Quantification of Hepatitis C Virus (HCV)-RNA is important for the
      clinical management of patients undergoing antiviral therapy. OBJECTIVES: To
      compare the quantification of clinical plasma samples by the Roche COBAS
      AmpliPrep/COBAS TaqMan HCV test v2.0 and the artus HCV QS-RGQ test. STUDY DESIGN:
      HCV-RNA viral load in 155 plasma samples from HCV-seropositive individuals was
      determined using the COBAS test and retrospectively with the artus. Furthermore,
      a dilution series of an Acrometrix standard was tested with both tests in
      replicates of five to assess differences in limit of detection and precision.
      RESULTS: Two clinical samples showed inhibition using the artus test and were
      excluded from analysis. Of the clinical samples, 20 tested negative in both
      tests, 7 tested positive in the COBAS test and negative in the artus test, and
      126 samples were quantified by both tests. The mean overall difference between
      tests (artus-COBAS) was 0.27 log IU/mL. The mean difference of quantification
      varied little across genotype 1a, 1b, 2b and 3a (range: +0.15 to +0.35 log
      IU/mL). Both tests were precise (%CV at 1000 IU/mL 1.1 and 1.8 for the COBAS and
      artus test, respectively). CONCLUSIONS: The limit of detection appeared lower in
      the COBAS test than the artus test when analyzed from a limited number of
      replicates. Both tests were precise with the artus test quantifying higher than
      the COBAS test on average. It is therefore recommended to monitor individual
      patients with the same test throughout treatment.

PMID- 24894602
TI  - SacPox from the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius is a
      proficient lactonase.
AB  - BACKGROUND: SacPox, an enzyme from the extremophilic crenarchaeal Sulfolobus
      acidocaldarius (Sac), was isolated by virtue of its phosphotriesterase (or
      paraoxonase; Pox) activity, i.e. its ability to hydrolyze the neurotoxic
      organophosphorus insecticides. Later on, SacPox was shown to belong to the
      Phosphotriesterase-Like Lactonase family that comprises natural lactonases,
      possibly involved in quorum sensing, and endowed with promiscuous,
      phosphotriesterase activity. RESULTS: Here, we present a comprehensive and broad
      enzymatic characterization of the natural lactonase and promiscuous
      organophosphorus hydrolase activities of SacPox, as well as a structural analysis
      using a model. CONCLUSION: Kinetic experiments show that SacPox is a proficient
      lactonase, including at room temperature. Moreover, we discuss the observed
      differences in substrate specificity between SacPox and its closest homologues
      SsoPox and SisLac together with the possible structural causes for these
      observations.

PMID- 24894604
TI  - Severe acute hepatitis E in an HIV infected patient: Successful treatment with
      ribavirin.
AB  - In industrialized countries, most cases of hepatitis E virus (HEV) infection in
      humans are autochthonous, mainly through foodborne and zoonotic transmission
      routes. In Europe, genotype 3 is a cause of acute self-limiting viral hepatitis,
      but can also be responsible for chronic hepatitis in immunocompromised patients.
      Ribavirin has been successfully used in the treatment of chronic hepatitis E and
      in a few cases of severe acute hepatitis E in immunocompetent patients. We report
      here the case of a 39 year-old man infected with HIV presenting with acute
      hepatitis E (genotype 3c). Unlike most cases, evolution was severe with a fall of
      prothrombin time down to 45%. Treatment with ribavirin allowed rapid viral
      clearance and a gradual normalization of liver function tests. 

PMID- 24894605
TI  - History of biological warfare and bioterrorism.
AB  - Bioterrorism literally means using microorganisms or infected samples to cause
      terror and panic in populations. Bioterrorism had already started 14 centuries
      before Christ, when the Hittites sent infected rams to their enemies. However,
      apart from some rare well-documented events, it is often very difficult for
      historians and microbiologists to differentiate natural epidemics from alleged
      biological attacks, because: (i) little information is available for times before
      the advent of modern microbiology; (ii) truth may be manipulated for political
      reasons, especially for a hot topic such as a biological attack; and (iii) the
      passage of time may also have distorted the reality of the past. Nevertheless, we
      have tried to provide to clinical microbiologists an overview of some likely
      biological warfare that occurred before the 18th century and that included the
      intentional spread of epidemic diseases such as tularaemia, plague, malaria,
      smallpox, yellow fever, and leprosy. We also summarize the main events that
      occurred during the modern microbiology era, from World War I to the recent
      'anthrax letters' that followed the World Trade Center attack of September 2001.
      Again, the political polemic surrounding the use of infectious agents as a weapon
      may distort the truth. This is nicely exemplified by the Sverdlovsk accident,
      which was initially attributed by the authorities to a natural foodborne
      outbreak, and was officially recognized as having a military cause only 13 years
      later.

PMID- 24894607
TI  - Si-H bond activation at {(NHC)2Ni0} leading to hydrido silyl and bis(silyl)
      complexes: a versatile tool for catalytic Si-H/D exchange, acceptorless
      dehydrogenative coupling of hydrosilanes, and hydrogenation of disilanes to
      hydrosilanes.
AB  - The unique reactivity of the nickel(0) complex [Ni2(iPr2Im)4(COD)] (1) (iPr2Im =
      1,3-di-isopropyl-imidazolin-2-ylidene) towards hydrosilanes in stoichiometric and
      catalytic reactions is reported. A series of nickel hydrido silyl complexes cis
      [Ni(iPr2Im)2(H)(SiH(n-1)R(4-n))] (n = 1, 2) and nickel bis(silyl) complexes cis
      [Ni(iPr2Im)2(SiH(n-1)R(4-n))2] (n = 1, 2, 3) were synthesized by stoichiometric
      reactions of 1 with hydrosilanes H(n)SiR(4-n), and fully characterized by X-ray
      diffraction and spectroscopic methods. These hydrido silyl complexes are examples
      where the full oxidative addition step is hindered. They have, as a result of the
      remaining Si-H interactions, remarkably short Si-H distances and feature a unique
      dynamic behavior in solution. Cis-[Ni(iPr2Im)2(H)(SiMePh2)] (cis-5) shows in
      solution at room temperature a dynamic site exchange of the NHC ligands, H-D
      exchange with C6D6 to give the deuteride complex cis-[Ni(iPr2Im)2(D)(SiMePh2)]
      (cis-5-D), and at elevated temperatures an irreversible isomerization to trans
      [Ni(iPr2Im)2(D)(SiMePh2)] (trans-5-D). Reactions with sterically less demanding
      silanes give cis-configured bis(silyl) complexes accompanied by the release of
      dihydrogen. These complexes display, similarly to the hydrido silyl complexes,
      interestingly short Si-Si distances. Complex 1 reacts with 4 eq. HSi(OEt)3, in
      contrast to all the other silanes used in this study, to give the trans
      configured bis(silyl) complex trans-[Ni(iPr2Im)2Ni(Si(OEt)3)2] (trans-12). The
      addition of two equivalents of Ph2SiH2 to 1 results, at elevated temperatures, in
      the formation of the dinuclear complex [{(iPr2Im)Ni-MU(2)-(HSiPh2)}2] (6). This
      diamagnetic, formal Ni(I) complex exhibits a long Ni-Ni bond in the solid state,
      as established by X-ray diffraction. The capability of the electron rich
      {Ni(iPr2Im)2} complex fragment to activate Si-H bonds was applied catalytically
      in the deuteration of Et3Si-H to Et3Si-D employing C6D6 as a convenient deuterium
      source. Furthermore, we show that 1 serves as a catalyst for the acceptorless
      dehydrogenative coupling of Ph2SiH2 to the corresponding disilane Ph2HSi-SiHPh2
      and trisilane Ph2HSi-Si(Ph)2-SiHPh2, and the coupling of PhSiH3 to give a mixture
      of cyclic and linear polysilanes with high polydispersity (M(w) = 1119; M(n) =
      924; M(w)/M(n) = 1.2). The capability of 1 to catalyze the formal reverse
      reaction as well is demonstrated by the hydrogenation of disilanes. The
      hydrogenation of the disilanes Ph2MeSi-SiMePh2 and PhMe2Si-SiMe2Ph to the
      corresponding hydrosilanes Ph2MeSi-H and PhMe2Si-H, respectively, proceeds
      effectively in the presence of 1 under very mild conditions (room temperature,
      1.8 bar H2 pressure).

PMID- 24894606
TI  - Increasing opportunistic oral cancer screening examinations: findings from focus
      groups with general dentists in Puerto Rico.
AB  - This study aims to identify educational and training modalities that dentists in
      Puerto Rico (PR) believe will increase the quality and quantity of opportunistic
      oral cancer screening examinations (OCS) in dental offices on the island. The
      study was conducted in three phases: a systematic search of relevant literature,
      an expert review and consensus panel, and focus groups (FG) involving PR general
      dentists. To increase OCS by dentists in PR, the FG participants proposed a small
      group, hands-on OCS training, an integrated oral cancer course, and readily
      available videos, photographs, and computer simulations to further demonstrate
      OCS performance and facilitate differential diagnosis. OCS training requirements
      for licensure and re-licensure, improving OCS dentist-patient communication
      skills, and establishment of an oral lesion referral center were also viewed
      favorably. In conclusion, general dentists in our FGs believed the quality and
      quantity of OCS in Puerto Rico can be increased through the application of
      specific continuing education and training modalities. 

PMID- 24894609
TI  - [The value of diagnostic ultrasound for intensive care medicine, surgery,
      anesthesia and emergency medicine].

PMID- 24894608
TI  - Belief-level markers of physical activity among young adult couples: comparisons
      across couples without children and new parents.
AB  - The health benefits of regular moderate-vigorous intensity physical activity
      (MVPA) are well established, yet young adults, particularly parents, often show
      declines in MVPA and may represent a critical population for intervention. Theory
      based correlates used to guide future interventions are scant in this population.
      The purpose of this study was to examine theory of planned behaviour (TPB) belief
      level constructs as correlates of directly assessed MVPA across cohorts of
      couples without children and with their first child over the initial 12 months.
      Participants were 238 adults (102 not expecting a child, 136 expecting first
      child) who completed baseline demographics, belief measures of the TPB and seven
      day accelerometry, followed by assessments at 6 and 12 months. Results showed
      select medium-sized belief-PA correlations with sex and cohort interactions.
      Overall, women had larger affect-based behavioural belief associations with MVPA
      than men (e.g. PA relieves stress), and among new parents, mothers showed larger
      associations with control over MVPA than fathers. Mothers also had larger
      associations between control beliefs and MVPA compared to women without children
      (e.g. domestic duties, bad weather). Extremely high means and low variability on
      the behavioural beliefs show limited room for possible changes in intervention
      while control beliefs had low means suggesting room for change. Interventions
      targeting control among new mothers may be paramount for increasing MVPA, yet the
      TPB yielded less insight into the targets for promoting MVPA among young men.

PMID- 24894610
TI  - [CME. Hypertension and salt intake: salt-free for all?].

PMID- 24894612
TI  - [Emergency ultrasound diagnosis of the thorax for internal medicine and
      traumatology patients].
AB  - Thoracic ultrasound has a high significance in emergency medicine. In case of
      dyspnoea, it leads quickly and reliably to the causative disease. Especially in
      differentiating lobar pneumonia from cardiogenic pulmonary oedema and lung
      embolism, it may be used with good confidence. After thoracic trauma, most of the
      injuries can be detected with sonography: lung contusion, pleural effusion,
      pericardial effusion, pneumothorax, rib fractures and sternal fractures. In
      clinically unstable patients, vital decisions can be made based on sonographic
      results. 

PMID- 24894613
TI  - [Focused surgical bedside ultrasound: E-FAST (focused assessment with sonography
      in trauma) - abdominal aortic aneurysm - cholecystolithiasis - acute
      appendicitis].
AB  - Ultrasound is an easy to learn and highly efficient diagnostic tool to complete
      the clinical examination and improve bedside decision-making. In the trauma room,
      surgeons are often required to make a quick decision as to whether or not a
      patient needs an emergency intervention or whether further diagnostics are
      required. For this reason, education of surgeons in performing focused emergency
      ultrasound is pivotal. The goal of ICAN is to improve and expand the education of
      surgeons in Switzerland. This article provides a short review of the most
      frequent surgical pathologies encountered in the emergency room. 

PMID- 24894614
TI  - [Implementation of focused ultrasonography in an acute care setting].
AB  - The legitimacy of intensivists and emergency physicians to use ultrasound in
      their daily practice is no longer questioned. This new tool is now considered
      essential in the acute care setting. After overcoming the technological and
      political obstacles, the current challenge is to implement technology in units.
      Here we give some recommendations based on our experience of the last fifteen
      years. 

PMID- 24894615
TI  - Point-of-care lung ultrasound.
AB  - Point-of-care lung ultrasound represents an emerging and useful technique in the
      management of pulmonary diseases. For many years, thoracic ultrasonography was
      limited to the study of pleural effusion and thoracic superficial masses because
      alveolar air and bones of the thoracic cage limit the propagation of the
      ultrasound beam. Only recently has been highlighted that, by the fact, lung
      ultrasound works like a real densitometer that is highly sensitive to variations
      of the pulmonary content and balance between air and fluids. Dynamic and static
      analysis of a combination of sonographic artifacts and real images makes it
      possible an accurate diagnosis of many lung disorders, particularly when lung
      ultrasound is applied in the emergency and critical care setting. Sonography is
      useful in the diagnostic process of lung diseases where the alveolar air is
      reduced and interstitial fluids are increased, but also when air or fluids are
      collected in the pleural space. This article analyzes the basic principles of
      point-of-care lung ultrasound and all the supposed limitations to the diagnostic
      usefulness of this technique. Moreover, the article reviews the three main fields
      of application for lung ultrasound: interstitial, alveolar and pleural syndromes.

PMID- 24894617
TI  - [Glucocorticoids effective in patients with knee osteoarthritis in lower dose].

PMID- 24894618
TI  - [Adding clopidogrel after stroke while on aspirin-does not help, only hurts].

PMID- 24894620
TI  - [CME ultrasound diagnosis 58. Epigastric incidental finding. Intraductal
      papillary mucinous neoplasia (IPMN)].

PMID- 24894623
TI  - A simple, safe, and effective method of cyst wall removal for Rathke's cleft
      cyst.

PMID- 24894622
TI  - Vaccinia reporter viruses for quantifying viral function at all stages of gene
      expression.
AB  - Poxviruses are a family of double stranded DNA viruses that include active human
      pathogens such as monkeypox, molluscum contagiousum, and Contagalo virus. The
      family also includes the smallpox virus, Variola. Due to the complexity of
      poxvirus replication, many questions still remain regarding their gene expression
      strategy. In this article we describe the conceptualization and usage of
      recombinant vaccinia viruses that enable real-time measurement of single and
      multiple stages of viral gene expression in a high-throughput format. This is
      enabled through the use of spectrally distinct fluorescent proteins as reporters
      for each of three stages of viral replication. These viruses provide a high
      signal-to-noise ratio while retaining stage specific expression patterns,
      enabling plate-based assays and microscopic observations of virus propagation and
      replication. These tools have uses for antiviral discovery, studies of the virus
      host interaction, and evolutionary biology. 

PMID- 24894624
TI  - Hyponatremia as a powerful prognostic predictor for Japanese patients with clear
      cell renal cell carcinoma treated with a tyrosine kinase inhibitor.
AB  - BACKGROUND: We aimed to evaluate the prognostic significance of hyponatremia in
      patients with metastatic clear cell renal cell carcinoma (RCC) treated with a
      tyrosine kinase inhibitor (TKI). METHODS: This study included a total of 209
      consecutive Japanese patients undergoing radical nephrectomy who were
      subsequently treated with either sunitinib or sorafenib as a first-line therapy
      for metastatic clear cell RCC. In this series, normal natremia and hyponatremia
      prior to the introduction of TKI was defined as a serum sodium level >136 and
      <=136 mEq/L, respectively. RESULTS: Patients were classified into 165 (78.9 %)
      with normal natremia and 44 (21.1 %) with hyponatremia. Progression-free survival
      (PFS) in the hyponatremia group (median 10.0 months) was significantly poorer
      than that in the normal natremia group (median 28.4 months). Overall survival
      (OS) in the hyponatremia group (median 20.9 months) was significantly poorer than
      that in the normal natremia group (median 38.5 months). Multivariate analyses
      identified hyponatremia, in addition to the existence of sarcomatoid components
      in radical nephrectomy specimens, high serum C-reactive protein levels, and low
      serum albumin levels, as poor prognostic factors for both PFS and OS. There were
      significant differences in both PFS and OS according to the number of these 4
      independent risk factors that were positive (negative for any risk factors vs
      positive for 1 or 2 risk factors vs positive for 3 or 4 risk factors).
      CONCLUSIONS: Hyponatremia appears to be one of the most powerful prognostic
      predictors in Japanese patients treated with a TKI as a first-line agent against
      metastatic clear cell RCC.

PMID- 24894625
TI  - Efficacy of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) co-administered with
      varenicline and counselling for smoking cessation: a randomized placebo
      controlled trial.
AB  - BACKGROUND AND AIMS: Nicotine vaccination has been proposed as a possible
      treatment to aid smoking cessation. First efficacy results of the nicotine
      vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30%
      antibody responders achieved higher abstinence rates than placebo. The present
      study examined the efficacy of adding NicVAX versus placebo to varenicline and
      behavioural support as an aid in smoking cessation and relapse prevention.
      DESIGN: Randomized placebo-controlled trial. SETTING: Two research centres
      (Maastricht University Medical Centre and Slotervaart Hospital) in the
      Netherlands. PARTICIPANTS: A total of 558 smokers were assigned randomly to six
      injections with NicVAX (n = 278) or placebo (n = 280) both co-administered with
      open label varenicline and behavioural support. MEASURES: Outcomes were prolonged
      carbon monoxide-validated abstinence from weeks 9 to 52 (primary) and weeks 37 to
      52 (secondary). We also performed a pre-planned subgroup analysis in the top 30%
      antibody responders. FINDINGS: There was no difference in abstinence rates
      between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR)
      = 0.89, 95% confidence interval (CI) = 0.62-1.29] or weeks 37 to 52 (33.8 versus
      33.2%, OR = 1.03, 95% CI = 0.73-1.46). The top 30% antibody responders, compared
      to the placebo group, showed a non-significant tendency towards higher abstinence
      rates from weeks 37 to 52 (42.2 versus 33.2%, OR = 1.47, 95% CI = 0.89-2.42).
      CONCLUSION: The nicotine vaccine, NicVAX, does not appear to improve the chances
      of stopping smoking when given in addition to varenicline and behavioural
      support.

PMID- 24894626
TI  - DNA methylation in Caulobacter and other Alphaproteobacteria during cell cycle
      progression.
AB  - In Caulobacter crescentus, methylation of DNA by CcrM plays an important part in
      the regulation of cell cycle progression. Thanks to this methyltransferase, the
      activity of which is cell cycle regulated, the chromosome transitions between a
      hemimethylated state in the S-phase to a fully methylated condition in the G1 and
      G2 phases. Any perturbation in CcrM expression, such as depletion or constitutive
      expression, causes severe developmental defects. Several studies suggest that the
      role of CcrM is conserved across the Alphaproteobacteria. In the past few years,
      the importance of methylation on the expression of cell cycle regulated genes has
      emerged, suggesting that CcrM-dependent methylation can direct the binding of
      transcription factors to specific methylated sequences and affect the expression
      of genes depending on the methylation state of their promoters. CcrM activity has
      recently been linked to GcrA, a cell cycle master regulator that controls the
      expression of several genes during S-phase. Here, we review recent findings that
      establish the global role of methylation in cell cycle progression, and also
      explore the significance of a CcrM-GcrA epigenetic module that has co-evolved in
      Alphaproteobacteria, including Caulobacter, in controlling several genes involved
      in cell division, polarity, and motility. 

PMID- 24894627
TI  - Putting together a scientific team: collaborative science.
AB  - One of the most enjoyable parts of a science career is collaborative team
      experiences and developing life-long social networks. When the hypothesis being
      tested requires innovative efforts greater than any single laboratory,
      collaboration becomes an essential component for success - everyone is a
      stakeholder and trust is the driving force. 

PMID- 24894628
TI  - Biofilms, flagella, and mechanosensing of surfaces by bacteria.
AB  - Formation of a bacterial biofilm is a developmental process that begins when a
      cell attaches to a surface, but how does a bacterial cell know it is on or near a
      surface in the first place? The phase of this 'swim-or-stick' switch is
      determined by a sensory transduction mechanism referred to as surface sensing,
      which involves the rotating bacterial flagellum. This review explores six
      bacterial species as models of flagellar mechanosensing of surfaces to understand
      the current state of our knowledge and the challenges that lie ahead. A common
      link between these bacteria is a requirement for the proper function of the
      flagellar motor stators that channel ions into the cell to drive flagellar
      rotation. Conditions that affect ion flow act as a signal that, ultimately,
      controls the master transcriptional regulatory circuits controlling the flagellar
      hierarchy and biofilm formation. 

PMID- 24894629
TI  - Dispersive liquid-phase microextraction with solidification of floating organic
      droplet coupled with high-performance liquid chromatography for the determination
      of Sudan dyes in foodstuffs and water samples.
AB  - Dispersive liquid-phase microextraction with solidification of floating organic
      drop (SFO-DLPME) is one of the most interesting sample preparation techniques
      developed in recent years. In this paper, a new, rapid, and efficient SFO-DLPME
      coupled with high-performance liquid chromatography (HPLC) was established for
      the extraction and sensitive detection of banned Sudan dyes, namely, Sudan I,
      Sudan II, Sudan III, and Sudan IV, in foodstuff and water samples. Various
      factors, such as the type and volume of extractants and dispersants, pH and
      volume of sample solution, extraction time and temperature, ion strength, and
      humic acid concentration, were investigated and optimized to achieve optimal
      extraction of Sudan dyes in one single step. After optimization of extraction
      conditions using 1-dodecanol as an extractant and ethanol as a dispersant, the
      developed procedure was applied for extraction of the target Sudan dyes from 2 g
      of food samples and 10 mL of the spiked water samples. Under the optimized
      conditions, all Sudan dyes could be easily extracted by the proposed SFO-DLPME
      method. Limits of detection of the four Sudan dyes obtained were 0.10-0.20 ng g(
      1) and 0.03 MUg L(-1) when 2 g of foodstuff samples and 10 mL of water samples
      were adopted, respectively. The inter- and intraday reproducibilities were below
      4.8% for analysis of Sudan dyes in foodstuffs. The method was satisfactorily used
      for the detection of Sudan dyes, and the recoveries of the target for the spiked
      foodstuff and water samples ranged from 92.6 to 106.6% and from 91.1 to 108.6%,
      respectively. These results indicated that the proposed method is simple, rapid,
      sensitive, and suitable for the pre-concentration and detection of the target
      dyes in foodstuff samples. 

PMID- 24894630
TI  - Women's perspectives of the fetal fibronectin testing process: a qualitative
      descriptive study.
AB  - BACKGROUND: In 2009 the Ontario Ministry of Health and Long Term Care funded the
      implementation of province-wide fetal fibronectin testing in Ontario hospitals.
      This paper reports results from the provincial evaluation that sought to describe
      the experience of fetal fibronectin testing from the perspective of women with
      symptoms of preterm labour. METHODS: A descriptive qualitative design was used,
      employing semi-structured telephone and face-to-face interviews with women who
      had fetal fibronectin testing. RESULTS: Five hospitals participated in recruiting
      women for the study and 17 women were interviewed. Women described their
      experiences of fetal fibronectin testing as an emotional process that moves from
      expecting, to feeling, to hoping for reassurance; and then to re-defining what is
      required to feel reassured. Women described feeling anxious while waiting for
      fetal fibronectin results. When test results were negative, women described
      feeling a sense of relief that their symptoms would not likely lead to an
      imminent preterm birth. Women with positive results expressed feeling reassured
      by the care decisions and quick action taken by the health care team. CONCLUSION:
      Fetal fibronectin testing was acceptable and beneficial to these women with
      symptoms of preterm labour. Implications for practice and future research are
      suggested.

PMID- 24894631
TI  - The FAM3 superfamily member ILEI ameliorates Alzheimer's disease-like pathology
      by destabilizing the penultimate amyloid-beta precursor.
AB  - Accumulation of amyloid-beta peptide (Abeta) in the brain underlies the
      pathogenesis of Alzheimer's disease (AD). Abeta is produced by beta- and gamma
      secretase-mediated sequential proteolysis of amyloid-beta precursor protein
      (APP). Here we identify a secretory protein named interleukin-like epithelial
      mesenchymal transition inducer (ILEI, also known as FAM3 superfamily member C) as
      a negative regulator of Abeta production. ILEI destabilizes the beta-secretase
      cleaved APP carboxy-terminal fragment, the penultimate precursor of Abeta, by
      binding to the gamma-secretase complex and interfering with its chaperone
      properties. Notch signalling and gamma-secretase activity are not affected by
      ILEI. We also show neuronal expression of ILEI and its induction by transforming
      growth factor-beta signalling. The level of secreted ILEI is markedly decreased
      in the brains of AD patients. Transgenic (Tg) overexpression of ILEI
      significantly reduces the brain Abeta burden and ameliorates the memory deficit
      in AD model mice. ILEI may be a plausible target for the development of disease
      modifying therapies. 

PMID- 24894632
TI  - Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal
      genetics? Comment.

PMID- 24894633
TI  - Development of high-performance liquid chromatographic for quality and
      authenticity control of Chinese propolis.
AB  - A RP-high-performance liquid chromatography (HPLC) method was developed for
      quality control of Chinese propolis by simultaneous analysis of 12 flavonoids and
      8 phenolic acids. The results showed that vanillic acid, rutin, myricetin, and
      luteolin were not detected in all of the analyzed propolis and poplar tree gum
      samples. The caffeic acid, ferulic acid and p-coumaric acid were not detected in
      poplar tree gum but were detected in propolis, which suggest that they are
      practical indexes of distinguishing propolis from poplar tree gum. The flavonoid
      profiles of poplar tree gum were found to be similar to those of propolis, which
      are dominated by pinobanksin, pinocembrin, 3-O-acetylpinobanksin, chrysin, and
      galangin. Therefore, the proposed method could be applied to exclude poplar tree
      gum from propolis with cafferic acid, ferulic acid, and p-coumaric acid as
      qualitative markers, and distinguish poplar source resin from other illegal
      substances, and evaluate the quality grading of poplar-type propolis with
      pinobanksin, pinocembrin, 3-O-acetylpinobanksin, chrysin, and galangin as
      qualitative and quantitative markers. 

PMID- 24894634
TI  - Development of communication by young people with cerebral palsy.

PMID- 24894635
TI  - Fabrication and characterization of Mg/P(LLA-CL)-blended nanofiber scaffold.
AB  - Poly(l-lactic acid-co-epsilon-caprolactone) (P(LLA-CL)) is a kind of copolymer
      polymerized from lactic acid and epsilon-caprolactone. Electrospun P(LLA-CL)
      nanofibers have good biocompatibility, biodegradability, and mechanical property.
      However, this type of nanofibers will produce acid groups during the degradation,
      so that, the pH value of the environment will decrease and result in tissue
      inflammation. On the other hand, Magnesium (Mg) alloy tissue engineering
      scaffolds will show alkaline during the degradation because of the
      electrochemical corrosion. Based on the principle of acid-based neutralization,
      combination of these two kinds of materials through electrospinning could keep
      the pH of the degradation environment neutral. In this paper, fabrication and
      characterization of Mg/P(LLA-CL)-blended nanofiber scaffolds with different
      ratios will be studied by scanning electron microscopy and universal materials
      testing machines to observe the morphology and mechanical properties of
      nanofibers, respectively. Furthermore, PIECs were cultured and seeded on the
      scaffolds for different time to evaluate the proliferation behavior on the
      scaffolds by MTT assay. The degradation tests of the samples lasted for three
      months in phosphate-buffered saline to evaluate the pH values of degradation
      solutions and the weight loss of nanofibers during degradation. The results
      showed that the mechanical property and biocompatibility of Mg/P(LLA-CL)-blended
      nanofibers were worse than that of pure P(LLA-CL). Moreover, the addition of Mg
      in the nanofibers accelerated the weight loss of the Mg/P(LLA-CL) blending fibers
      and increased the pH values of the environment during degradation of Mg/P(LLA-CL)
      blended nanofibers.

PMID- 24894636
TI  - Photo-activated ionic gelation of alginate hydrogel: real-time rheological
      monitoring of the two-step crosslinking mechanism.
AB  - We examine the gelation of alginate undergoing ionic crosslinking upon
      ultraviolet (UV) irradiation using in situ dynamic rheology. Hydrogels are formed
      by combining alginate with calcium carbonate (CaCO3) particles and a photoacid
      generator (PAG). The PAG is photolyzed upon UV irradiation, resulting in the
      release of free calcium ions for ionic crosslinking. The viscous and elastic
      moduli during gelation are monitored as a function of the UV irradiation
      intensity, exposure time, alginate concentration, and the ratio between alginate
      and calcium carbonate. Gel time decreases as irradiation intensity increases
      because a larger concentration of PAG is photolyzed. Interestingly, dark curing,
      the continuing growth of microstructure in the absence of UV light, is observed.
      In some instances, the sample transitions from a solution to a gel during the
      dark curing phase. Additionally, when exposed to constant UV irradiation after
      the dark curing phase, samples reach the same plateau modulus as samples exposed
      to constant UV without dark curing, implying that dark curing does not affect the
      gelation mechanism. We believe the presence of dark curing is the result of the
      acidic environment persisting within the sample, allowing CaCO3 to dissociate,
      thereby releasing free Ca(2+) ions capable of binding with the available
      appropriate ionic blocks of the polymer chains. The growth of microstructure is
      then detected if the activation barrier has been crossed to release sufficient
      calcium ions. In this regard, we calculate a value of 30 J that represents the
      activation energy required to initiate gelation. 

PMID- 24894637
TI  - Dynamic-locking-screw (DLS)-leads to less secondary screw perforations in
      proximal humerus fractures.
AB  - BACKGROUND: Loss of reduction and screw perforation causes high failure rates in
      the treatment of proximal humerus fractures. The purpose of the present study was
      to evaluate the early postoperative complications using modern Dynamic Locking
      Screws (DLS 3.7) for plating of proximal humerus fractures. METHODS: Between
      03/2009 and 12/2010, 64 patients with acute proximal humerus fractures were
      treated by angular stable plate fixation using DLSs in a limited multi-centre
      study. Follow-up examinations were performed three, six, twelve and twenty-four
      weeks postoperatively and any complications were carefully collected. RESULTS: 56
      of 64 patients were examined at the six-month follow-up. Complications were
      observed in 12 patients (22%). In five cases (9%), a perforation of the DLS 3.7
      occurred. CONCLUSIONS: Despite the use of modern DLS 3.7, the early complications
      after plating of proximal humerus fractures remain high. The potential advantage
      of the DLS 3.7 regarding secondary screw perforation has to be confirmed by
      future randomized controlled trials.

PMID- 24894638
TI  - A brief historical perspective on dental implants, their surface coatings and
      treatments.
AB  - This review highlights a brief, chronological sequence of the history of dental
      implants. This historical perspective begins with ancient civilizations and
      spotlights predominant dentists and their contributions to implant development
      through time. The physical, chemical and biologic properties of various dental
      implant surfaces and coatings are discussed, and specific surface treatments
      include an overview of machined implants, etched implants, and sand-blasted
      implants. Dental implant coatings such as hydroxyapatite, fluoride, and statin
      usage are further reviewed. 

PMID- 24894639
TI  - Increased trabecular volumetric bone mass density in Familial Hypocalciuric
      Hypercalcemia (FHH) type 1: a cross-sectional study.
AB  - Familial Hypocalciuric Hypercalcaemia (FHH) Type 1 is caused by an inactivating
      mutation in the calcium-sensing receptor (CASR) gene resulting in elevated plasma
      calcium levels. We investigated whether FHH is associated with change in bone
      density and structure. We compared 50 FHH patients with age- and gender-matched
      population-based controls (mean age 56 years, 69 % females). We assessed areal
      BMD (aBMD) by DXA-scans and total, cortical, and trabecular volumetric BMD (vBMD)
      as well as bone geometry by quantitative computed tomography (QCT) and High
      Resolution peripheral-QCT (HR-pQCT). Compared with controls, FHH females had a
      higher total and trabecular hip vBMD and a lower cortical vBMD and hip bone
      volume. Areal BMD and HRpQCT indices did not differ except an increased
      trabecular thickness and an increased vBMD at the transition zone between
      cancellous and cortical bone in of the tibia in FHH. Finite element analyses
      showed no differences in bone strength. Multiple regression analyses revealed
      correlations between vBMD and P-Ca(2+) levels but not with P-PTH. Overall, bone
      health does not seem to be impaired in patients with FHH. In FHH females, bone
      volume is decreased, with a lower trabecular volume but a higher vBMD, whereas
      cortical vBMD is decreased in the hip. This may be due to either an impaired
      endosteal resorption or corticalization of trabecular bone. The smaller total
      bone volume suggests an impaired periosteal accrual, but bone strength is not
      impaired. The findings of more pronounced changes in females may suggest an
      interaction between sex hormones and the activity of the CaSR on bone. 

PMID- 24894640
TI  - Molecular stratification of medulloblastoma: comparison of histological and
      genetic methods to detect Wnt activated tumours.
AB  - AIMS: Wnt activation in medulloblastomas is associated with good outcome. Upfront
      testing and risk-adapted stratification of patients will be done in future
      clinical studies. In a cohort of 186 paediatric medulloblastomas our aim was to
      identify the optimal methods in standard clinical practice to detect this
      subgroup. METHODS: Nuclear accumulation of beta-catenin was analysed by
      immunohistochemistry (IHC). DNA of FFPE tissue was amplified by PCR for single
      strand conformation polymorphism analysis and direct sequencing of CTNNB1 exon 3.
      Copy number of chromosome 6 was analysed by multiplex ligation-dependent probe
      amplification and molecular inversion profiling. RESULTS: Different automated
      immunostaining systems showed similar results. Twenty-one of 186 samples had
      nuclear accumulation in >=5% of cells, 17 samples showed <5% beta-catenin
      positive nuclei. None of these 17 cases had CTNNB1 mutations, but 18 of 21 cases
      with >=5% accumulation did, identifying these 18 cases as Wnt-subgroup
      medulloblastomas. Fifteen of 18 mutated cases showed monosomy 6, 3 had balanced
      chromosome 6. On the contrary, none of the CTNNB1 wild-type tumours had monosomy
      6. CONCLUSIONS: Standard neuropathological evaluation of medulloblastoma samples
      should include IHC of beta-catenin because tumours with high nuclear accumulation
      of beta-catenin most probably belong to the Wnt subgroup of medulloblastomas.
      Still, IHC alone may be insufficient to detect all Wnt cases. Similarly,
      chromosome 6 aberrations were not present in all CTNNB1-mutated cases. Therefore,
      we conclude that sequencing analysis of CTNNB1 exon 3 in combination with beta
      catenin IHC (possibly as pre-screening method) is a feasible and cost-efficient
      way for the determination of Wnt medulloblastomas.

PMID- 24894641
TI  - Minimally destructive sampling of type specimens of Pyropia (Bangiales,
      Rhodophyta) recovers complete plastid and mitochondrial genomes.
AB  - Plant species, including algae and fungi, are based on type specimens to which
      the name of a taxon is permanently attached. Applying a scientific name to any
      specimen therefore requires demonstrating correspondence between the type and
      that specimen. Traditionally, identifications are based on morpho-anatomical
      characters, but recently systematists are using DNA sequence data. These studies
      are flawed if the DNA is isolated from misidentified modern specimens. We propose
      a genome-based solution. Using 4 * 4 mm(2) of material from type specimens, we
      assembled 14 plastid and 15 mitochondrial genomes attributed to the red algae
      Pyropia perforata, Py. fucicola, and Py. kanakaensis. The chloroplast genomes
      were fairly conserved, but the mitochondrial genomes differed significantly among
      populations in content and length. Complete genomes are attainable from 19(th)
      and early 20(th) century type specimens; this validates the effort and cost of
      their curation as well as supports the practice of the type method. 

PMID- 24894642
TI  - Papillon-Lefevre syndrome with homozygous nonsense mutation of cathepsin C gene
      presenting with late-onset periodontitis.
AB  - Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder of
      keratinization caused by homozygous mutations in the gene encoding lysosomal
      protease cathepsin C (CTSC). It is clinically characterized by transgredient
      palmoplantar keratoderma (PPK) and periodontitis. A 15-year-old boy presenting
      with PPK from the age of 6 months and late-onset periodontitis that began at the
      age of 12 years is described. Mutation analysis revealed a homozygous nonsense
      mutation (p.Y304X) in exon 7 of the CTSC gene. Late-onset periodontitis in a
      patient with Papillon-Lefevre syndrome is a rare phenotypic variation. 

PMID- 24894643
TI  - Retroperitoneal drainage versus no drainage after pelvic lymphadenectomy for the
      prevention of lymphocyst formation in patients with gynaecological malignancies.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in Issue 1, 2010. Pelvic lymphadenectomy is associated with significant
      complications including lymphocyst formation and related morbidities.
      Retroperitoneal drainage using suction drains has been recommended as a method to
      prevent such complications. However, this policy has been challenged by the
      findings from recent studies. OBJECTIVES: To assess the effects of
      retroperitoneal drainage versus no drainage after pelvic lymphadenectomy on
      lymphocyst formation and related morbidities in gynaecological cancer patients.
      SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Specialised
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue
      12) in The Cochrane Library, electronic databases MEDLINE (Nov Week 3, 2013),
      EMBASE (2014, week 1), and the citation lists of relevant publications. The
      latest searches were performed on 10 January 2014. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) that compared the effect of retroperitoneal drainage
      versus no drainage after pelvic lymphadenectomy in gynaecological cancer
      patients. Retroperitoneal drainage was defined as placement of passive or active
      suction drains in pelvic retroperitoneal spaces. No drainage was defined as no
      placement of passive or active suction drains in pelvic retroperitoneal spaces.
      DATA COLLECTION AND ANALYSIS: We assessed studies using methodological quality
      criteria. For dichotomous data, we calculated risk ratios (RRs) and 95%
      confidence intervals (CIs). We examined continuous data using mean difference
      (MD) and 95% CI. MAIN RESULTS: Since the last version of this review, no new
      studies have been identified for inclusion. The review included four studies with
      571 participants. Considering the short-term outcomes (within four weeks after
      surgery), retroperitoneal drainage was associated with a comparable rate of
      overall lymphocyst formation when all methods of pelvic peritoneum management
      were considered together (two studies, 204 patients; RR 0.76, 95% CI 0.04 to
      13.35). When the pelvic peritoneum was left open, the rates of overall lymphocyst
      formation (one study, 110 patients; RR 2.29, 95% CI 1.38 to 3.79) and symptomatic
      lymphocyst formation (one study, 137 patients; RR 3.25, 95% CI 1.26 to 8.37) were
      higher in the drained group. At 12 months after surgery, the rates of overall
      lymphocyst formation were comparable between the groups (one study, 232 patients;
      RR 1.48, 95% CI 0.89 to 2.45). However, there was a trend toward increased risk
      of symptomatic lymphocyst formation in the group with drains (one study, 232
      patients; RR 7.12, 95% CI 0.89 to 56.97). The included trials were of low to
      moderate risk of bias. AUTHORS' CONCLUSIONS: Placement of retroperitoneal tube
      drains has no benefit in prevention of lymphocyst formation after pelvic
      lymphadenectomy in patients with gynaecological malignancies. When the pelvic
      peritoneum is left open, the tube drain placement is associated with a higher
      risk of short and long-term symptomatic lymphocyst formation.

PMID- 24894644
TI  - The performance of gradient alloy quantum dots in cell labeling.
AB  - The interest in using quantum dots (QDots) as highly fluorescent and photostable
      nanoparticles in biomedicine is vastly increasing. One major hurdle that slows
      down the (pre)clinical translation of QDots is their potential toxicity. Several
      strategies have been employed to optimize common core-shell QDots, such as the
      use of gradient alloy (GA)-QDots. These particles no longer have a size-dependent
      emission wavelength, but the emission rather depends on the chemical composition
      of the gradient layer. Therefore, particles of identical sizes but with emission
      maxima spanning the entire visible spectrum can be generated. In the present
      study, two types of GA-QDots are studied with respect to their cytotoxicity and
      cellular uptake. A multiparametric cytotoxicity approach reveals concentration
      dependent effects on cell viability, oxidative stress, cell morphology and cell
      functionality (stem cell differentiation and neurite outgrowth), where the
      particles are very robust against environmentally-induced breakdown. Non-toxic
      concentrations are defined and compared to common core-shell QDots analyzed under
      identical conditions. Additionally, this value is translated into a functional
      value by analyzing the potential of the particles for cell visualization.
      Interestingly, these particles result in clear endosomal localization, where
      different particles result in identical intracellular distributions. This is in
      contrast with CdTe QDots with the same surface coating, which resulted in clearly
      distinct intracellular distributions as a result of differences in nanoparticle
      diameter. The GA-QDots are therefore ideal platforms for cell labeling studies
      given their high brightness, low cytotoxicity and identical sizes, resulting in
      highly similar intracellular particle distributions which offer a lot of
      potential for optimizing drug delivery strategies. 

PMID- 24894645
TI  - Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing
      plasmid delivery.
AB  - Targeted delivery of therapeutic genes to the tumor site is critical for
      successful and safe cancer gene therapy. The arginine grafted bio-reducible poly
      (cystamine bisacrylamide-diaminohexane, CBA-DAH) polymer (ABP) conjugated poly
      (amido amine) (PAMAM), PAM-ABP (PA) was designed previously as an efficient gene
      delivery carrier. To achieve high efficacy in cancer selective delivery, we
      developed the tumor targeting bio-reducible polymer, PA-PEG1k-RGD, by conjugating
      cyclic RGDfC (RGD) peptides, which bind alphavbeta3/5 integrins, to the PAM-ABP
      using polyethylene glycol (PEG, 1 kDa) as a spacer. Physical characterization
      showed nanocomplex formation with bio-reducible properties between PA-PEG1k-RGD
      and plasmid DNA (pDNA). In transfection assays, PA-PEG1k-RGD showed significantly
      higher transfection efficiency in comparison with PAM-ABP or PA-PEG1k-RAD in
      alphavbeta3/5 positive MCF7 breast cancer and PANC-1 pancreatic cancer cells. The
      targeting ability of PA-PEG1k-RGD was further established using a competition
      assay. To confirm the therapeutic effect, the VEGF siRNA expressing plasmid was
      constructed and then delivered into cancer cells using PA-PEG1k-RGD. PA-PEG1k-RGD
      showed 20-59% higher cellular uptake rate into MCF7 and PANC-1 than that of non
      targeted polymers. In addition, MCF7 and PANC-1 cancer cells transfected with PA
      PEG1k-RGD/pshVEGF complexes had significantly decreased VEGF gene expression (51
      71%) and cancer cell viability (35-43%) compared with control. These results
      demonstrate that a tumor targeting bio-reducible polymer with an anti-angiogenic
      therapeutic gene could be used for efficient and safe cancer gene therapy. 

PMID- 24894646
TI  - Morphology and functions of astrocytes cultured on water-repellent fractal
      tripalmitin surfaces.
AB  - In the brain, astrocytes play an essential role with their multiple functions and
      sophisticated structure, as surrounded by a fractal environment which has not
      been available in our traditional cell culture. Water-repellent fractal
      tripalmitin (PPP) surfaces can imitate the fractal environment in vivo, so the
      morphology and biochemical characterization of astrocytes on these surfaces are
      examined. Water-repellent fractal PPP surface can induce astrocytes to display
      sophisticated morphology with smaller size of cell area, longer and finer
      filopodium-like processes, and higher morphological complexity. The super water
      repellent fractal PPP surface with water contact angle of 150 degrees ~160
      degrees  produces the maximal effects compared with other surfaces at lower water
      contact angles. The trends of characteristic protein expression, including that
      of nestin, vimentin, GFAP and glutamine synthetase, for astrocytes cultured on
      super water-repellent fractal PPP surfaces approximate more to in vivo pattern.
      The super water-repellent PPP surface also render astrocytes to perform more
      pronounced promotion of neurogenesis by increasing the release of nerve growth
      factor in a co-culture system. Altogether, our results suggest that the super
      water-repellent fractal PPP surface facilitates the astrocytes to mimic their in
      vivo performance, thus provides a closer-to-natural culture environment for
      experimental assessment of glial structure and functions. 

PMID- 24894647
TI  - Substrate selectivity of bacterial monoacylglycerol lipase based on crystal
      structure.
AB  - Lipases, which are conserved from bacteria to mammals, catalyze the hydrolysis of
      acylglycerol to free fatty acids and glycerol. Monoacylglycerol lipase (MGL)
      specifically catalyzes the hydrolysis of monoacylglycerol. Although there have
      been numerous studies of the structure of lipases, there have been few studies of
      MGL. Here, we report the crystal structure of authentic MGL isolated from
      Bacillus sp. H257 (bMGL). The crystal diffracts to 1.96 A resolution. It belongs
      to space group P21212, and the unit cell parameters are a=99.7 A, b=106.1 A and
      c=43.0 A. As in other lipases, three structural features for lipase activity are
      conserved in bMGL: the glycine-X-serine-X-glycine motif, catalytic triad and cap
      region. The structure of bMGL appears to be closed, as the cap region covers the
      active site entrance. The isolated bMGL hydrolyzed 2-AG, a known human MGL
      specific substrate. Based on a 2-AG bound model, we discuss the substrate
      selectivity. The functional and structural features of bMGL provide insight how
      its substrate selectivity is determined and how specific inhibitors of bacterial
      MGL could be designed, which may be useful for development of novel antibiotics.

PMID- 24894649
TI  - Coping With Stillbirth Among Ultraorthodox Jewish Women.
AB  - Stillbirth is a traumatic prenatal loss with personal, familial, and social
      implications. We explored the meaning of stillbirth for ultraorthodox Israeli
      women for whom grieving for prenatal loss derived from the power of faith. We
      conducted semistructured interviews with ten ultraorthodox women, ages 26 to 55,
      in a qualitative study that was focused on thematic content analysis and
      influenced by the phenomenological-hermeneutic tradition. The loss of the fetus
      was experienced as a test to the women's belief in God, and was perceived as a
      way to experience God's love. The women's faith became stronger and provided
      relief, calm, and confidence in God as benefactor. The meanings they attributed
      to their losses enabled them to move on. Findings are discussed in the context of
      research and theoretical literature on coping, bereavement, and mourning
      processes, and meaning for pregnancy-related losses. Awareness of ethnic meanings
      of stillbirth promotes implementation of culture-sensitive psychosocial
      interventions.

PMID- 24894648
TI  - Crystal structure of tRNA m(1)A58 methyltransferase TrmI from Aquifex aeolicus in
      complex with S-adenosyl-L-methionine.
AB  - The N (1)-methyladenosine residue at position 58 of tRNA is found in the three
      domains of life, and contributes to the stability of the three-dimensional L
      shaped tRNA structure. In thermophilic bacteria, this modification is important
      for thermal adaptation, and is catalyzed by the tRNA m(1)A58 methyltransferase
      TrmI, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. We present the
      2.2 A crystal structure of TrmI from the extremely thermophilic bacterium Aquifex
      aeolicus, in complex with AdoMet. There are four molecules per asymmetric unit,
      and they form a tetramer. Based on a comparison of the AdoMet binding mode of A.
      aeolicus TrmI to those of the Thermus thermophilus and Pyrococcus abyssi TrmIs,
      we discuss their similarities and differences. Although the binding modes to the
      N6 amino group of the adenine moiety of AdoMet are similar, using the side chains
      of acidic residues as well as hydrogen bonds, the positions of the amino acid
      residues involved in binding are diverse among the TrmIs from A. aeolicus, T.
      thermophilus, and P. abyssi.

PMID- 24894650
TI  - A phase I safety and pharmacokinetic study of ABT-263 in combination with
      carboplatin/paclitaxel in the treatment of patients with solid tumors.
AB  - Bcl-2 family proteins are the key regulators of the intrinsic apoptotic pathway,
      controlling the point-of no-return and setting the threshold to engage the death
      machinery in response to chemical damage. Bcl-2 proteins have emerged as
      attractive targets for anti-cancer drug development. Navitoclax is a selective,
      potent, orally bioavailable, small molecule Bcl-2 inhibitor. Primary endpoints
      assessed the safety and pharmacokinetic (PK) interactions between navitoclax in
      combination with carboplatin/paclitaxel or paclitaxel alone in patients with
      solid tumors The study comprised two arms, one a combination of navitoclax with
      paclitaxel and carboplatin, the second with navitoclax and paclitaxel alone.
      Nineteen patients were enrolled in this study. The most frequently reported
      treatment-emergent AEs were alopecia (57.9 %), anemia (52.6 %), nausea (52.6 %),
      constipation (42.1 %), diarrhea (42.1 %), fatigue (42.1 %), neutropenia (36.8 %),
      thrombocytopenia (36.8 %), vomiting (31.6 %), decreased appetite (31.6 %),
      dehydration (26.3 %), and hypomagnesaemia (26.3 %). In the light of significant
      hematological and non-hematological toxicity the study was ended before de
      escalation of navitoclax. Only one partial response was obtained at any dose
      tested, thus lowering doses could not have increased efficacy. It is the
      combination of toxicity with modest efficacy that led to discontinuation. No
      apparent PK interaction was observed between navitoclax and carboplatin or
      paclitaxel and the combination of navitoclax and paclitaxel had modest anti-tumor
      activity.

PMID- 24894653
TI  - Accuracy of non-operative identification of the sentinel lymph node using
      combined gamma and ultrasound scanning.
AB  - AIM: To assess how accurately the sentinel lymph node (SLN) can be identified
      percutaneously, using gamma probe and ultrasound technology. MATERIALS AND
      METHODS: Women with breast cancer, scheduled for wide local excision or
      mastectomy with SLN biopsy (SLNB), were included. Peri-areolar intradermal
      injection of technetium-99 nanocolloid was performed on the morning of surgery
      and 1-2 ml of blue dye was injected in the peri-areolar region once the patient
      was anaesthetized. Prior to surgery, a gamma probe was used over the skin to
      identify any hot spot that could represent a SLN. Ultrasound, guided by the hot
      spot, was then used to visualize potential SLNs and guide the insertion of a
      localizing wire. The accuracy in localizing the SLN by preoperative gamma-probe
      guided ultrasonography was assessed by comparison to SLNB. RESULTS: A SLN was
      correctly identified and marked using gamma-probe guided ultrasonography in 44 of
      59 cases (75%; 95% CI: 63-86%). CONCLUSION: This study supports the case for
      investigating percutaneous gamma probe and ultrasound guided interventions in the
      axilla in women with breast cancer, as a potential alternative to surgical SLNB.

PMID- 24894651
TI  - Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of
      EMD 1201081 in combination with cetuximab in second-line cetuximab-naive patients
      with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M
      SCCHN).
AB  - AIM: To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had
      antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of
      the head and neck (R/M SCCHN). METHODS: This was a phase 2, open-label,
      randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab
      (combination) vs cetuximab monotherapy (control) in cetuximab-naive patients with
      R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was
      permitted after progression. RESULTS: Objective response rate in both arms was
      5.7% (95% CI 1.2-15.7%) by independent assessment. Disease control was 37.7% for
      patients on combination (24.8-52.1%) and 43.4% on control (29.8-57.7%). Neither
      independent nor investigator assessments showed significant differences between
      study arms. Median progression-free survival was 1.5 months (1.3-2.6) for
      patients on combination, and 1.9 months (1.5-2.9) on control. The most frequent
      adverse events in the combination arm were rash (29.6%), acneiform dermatitis
      (22.2%), and injection site reactions (20.4%). Grade 3/4 dyspnea and hypokalemia
      were more frequent with cetuximab monotherapy (7.5% and 5.7% vs 1.9% each,
      respectively), and grade 3/4 respiratory failure and disease progression were
      more frequent with combination (5.6% each vs 1.9% each). CONCLUSION: EMD 1201081
      was well tolerated combined with cetuximab, but there was no incremental clinical
      efficacy.

PMID- 24894654
TI  - Retracted: Can the transtheoretical model motivate patients with coronary heart
      disease to exercise?
AB  - Li-Xia Zhu, Shuk-Ching Ho, Janet WH Sit and Hong-Gu He The above article from
      Nursing & Health Sciences, "Can the transtheoretical model motivate patients with
      coronary heart disease to exercise?" by Li-Xia Zhu, Shuk-Ching Ho, Janet WH Sit
      and Hong-Gu He, published online on 4th June 2014 on Wiley Online Library
      (wileyonlinlibrary.com) DOI: 10.1111/nhs.12150, has been retracted by agreement
      between the lead author, the journal's Editor in Chief, Teresa Stone, and Wiley
      Publishing Asia Pty Ltd. The retraction has been agreed due to the main study
      having been previously published. References to the previously published
      articles: Zhu L-X, Ho S-C, Sit JWH, He H-G. The effects of a transtheoretical
      model-based exercise stage-matched intervention on exercise behavior in patients
      with coronary heart disease: A randomized controlled trial. Patient Educ. Couns.
      2014; 95: 384-392. http://www.pec-journal.com/article/S0738-3991(14)00129
      3/abstract Zhu L-X, Ho S-C, Sit JWH, He H-G. Effects of a transtheoretical model
      based exercise stage-matched intervention on exercise behaviour and quality of
      life in patients with coronary heart disease: a randomized controlled trial. J.
      Adv. Nurs. 2014. doi:10.1111/jan.12469
      http://onlinelibrary.wiley.com/doi/10.1111/jan.12469/abstract Zhu L-X, Ho S-C,
      Sit JWH, He H-G. Effect of a transtheoretical model-based stage-matched exercise
      intervention on exercise behavior and angina in patients with coronary heart
      disease: a randomized controlled trial. J. Cardiovasc. Nurs. 2014. DOI:
      10.1097/JCN.0000000000000162.
      http://journals.lww.com/jcnjournal/Citation/publishahead/Effect_of_a_Transtheoret
      cal_Model_Based.99700.aspx.

PMID- 24894652
TI  - A Phase II study of bevacizumab in combination with trastuzumab and docetaxel in
      HER2 positive metastatic breast cancer.
AB  - BACKGROUND: Preclinical and early clinical data support the use of Vascular
      Epithelial Growth Factor (VEGF)-targeted therapy with trastuzumab in Human
      Epidermal Receptor 2 (HER2) positive breast cancer. Adding bevacizumab to a
      taxane (docetaxel or paclitaxel) improves progression free survival (PFS) of
      metastatic breast cancer (MBC) patients. OBJECTIVES: We evaluated the efficacy
      and feasibility of combining bevacizumab with trastuzumab and docetaxel in
      patients with HER2- positive MBC who received 0-1 prior chemotherapy regimens for
      metastatic disease. The primary end point was PFS. MATERIALS AND METHODS:
      Eligible patients received bevacizumab (15 mg/kg), trastuzumab (8 mg/kg loading
      dose followed by 6 mg/kg), and docetaxel (100 mg/m2 initially, later amended to
      75 mg/m2) every three weeks for six cycles and then were allowed to receive
      bevacizumab and trastuzumab alone. Results Thirteen (50%) of 26 patients enrolled
      completed all 6 cycles of bevacizumab, trastuzumab and docetaxel and went on to
      receive bevacizumab and trastuzumab alone (median: 11 cycles). The most common
      grade 3 or 4 toxicities include: neutropenia (8%), septic death (4%), infection
      not associated with neutropenia (15%), fatigue (27%), mylagia and/or arthraligia
      (20%), and hand-foot syndrome (8%). One patient (4%) and six patients (23%)
      developed grade 3 and grade 2 hypertension, respectively. Two (8%) patients had
      transient grade 2 drop in Left Ventricular Ejection Fraction (LVEF) with full
      recovery later. The median progression free survival (PFS) was 14.3 months (95%
      CI: 9.3-35 months), the objective response rate (ORR), defined as the best
      response of complete response (CR) or partial response (PR) was (12/26) 46%. The
      clinical benefit rate (CBR), defined as the best response of CR or PR or stable
      disease (SD) for at least 24 weeks, was (18/26) 69% (95% CI: 48-86%). CONCLUSION:
      The combination of bevacizumab, trastuzumab and docetaxel is well tolerated and
      is clinically active in patients with HER2-positive MBC, with response rate and
      PFS comparable to previous reports utilizing higher dose of docetaxel (100
      mg/m2). Recent randomized trials did not demonstrate additional overall survival
      (OS) benefit of adding bevacizumab to trastuzumab and docetaxel despite an
      improvement in PFS. Identification of predictive biomarkers and careful patient
      selection should be incorporated in further investigation of anti-VEGF in breast
      cancer.

PMID- 24894655
TI  - Apoptosis-like events and in vitro fertilization capacity of sex-sorted bovine
      sperm.
AB  - This study utilized three staining assays (Annexin V, mitochondrial membrane
      potential (JC-1) and TUNEL) for flow cytometric analysis of apoptosis in sex
      sorted sperm from four different bulls (A, B, C and D). Correlations between
      sperm quality and IVF efficiency were then assessed to determine which assay
      provided the best prediction of IVF efficiency. The results of the Annexin V
      assays, as well as measures of viable sperm, early apoptosis, necrotic sperm and
      mitochondrial membrane potential (?psim) showed that the sex-sorted sperm
      collected from bull A significantly differed from those of the other three bulls
      (p < 0.05). In addition, the levels of DNA fragmentation in sex-sorted sperm from
      bull A were significantly lower than those from bulls B and C (p < 0.05). The
      percentage of cells reaching the cleavage and blastocyst stages in sex-sorted
      sperm from bull A were significantly greater than those from the other bulls (p <
      0.05). A significant positive correlation was observed between viable sperm and
      the percentage of cells at the cleavage or blastocyst stages (p < 0.05). In
      contrast, a negative correlation was found between early apoptotic sperm and the
      percentage of cells at the cleavage or blastocyst stages (p < 0.05). In
      conclusion, these results indicated that the Annexin V assay was the most
      reliable technique for the prediction of the IVF success of sex-sorted bovine
      sperm.

PMID- 24894656
TI  - The effect of the setting of a positive surgical margin in soft tissue sarcoma.
AB  - BACKGROUND: The objectives of this study were to evaluate the risk of local
      recurrence and survival after soft tissue sarcoma (STS) resection with positive
      margins and to evaluate the safety of sparing adjacent critical structures.
      METHODS: One hundred sixty-nine patients with localized STS who had positive
      resection margins were identified from a prospective database. Patients who had
      positive margins were stratified into 3 groups, each representing a specific
      clinical scenario: critical structure positive margin (eg major nerve, vessel, or
      bone), tumor bed resection positive margin, and unexpected positive margin. The
      rates of local recurrence-free survival (LRFS) and cause-specific survival (CSS)
      were calculated and compared with relevant control patients who had negative
      margins after STS resection. RESULTS: After planned close dissection to preserve
      critical structures, the 5-year LRFS and CSS rates both depended on the quality
      of the surgical margins (97% and 80.3%, respectively, for those with negative
      margins vs 85.4% and 59.4%, respectively, for those with positive margins; P =
      .015 and P = .05, respectively). Negative margins achieved through resection of
      critical structures because of tumor invasion or encasement only slightly
      improved the 5-year rates of LRFS (91.2%) and CSS (63.6%; P = .8 and P = .9,
      respectively). The lowest 5-year LRFS and CSS rates were 63.4% and 59.2%,
      respectively, after an unexpected positive margin during primary surgery.
      CONCLUSIONS: After patients undergo resection of STS with positive margins,
      oncologic outcomes can be predicted based on the clinical context. Sparing
      adjacent critical structures in this setting is safe and contributes to improved
      functional outcomes.

PMID- 24894657
TI  - Cardiopulmonary exercise testing before liver surgery.
AB  - BACKGROUND: Cardiopulmonary exercise testing (CPET) assessed "poorer" fitness
      correlates with poorer outcomes in blinded studies. Whether this correlation will
      persist when CPET is utilized to stratify care as part of a multi-modal enhanced
      recovery after surgery (ERAS) program is unclear. This study examined whether
      CPET variables were associated with postoperative morbidity in patients
      undergoing hepatectomy within an ERAS program. OBJECTIVES AND METHODS: Data were
      prospectively collected on patients undergoing elective hepatectomy between
      October 2009 and April 2011. The relationships between CPET derived variables;
      postoperative complications and length of stay were investigated. RESULTS: Of 267
      patients undergoing surgery, 197 had undergone standard cycle ergometer CPET. The
      relative oxygen uptake [VO2 (ml kg(-1) min(-1))] and ventilatory equivalent of
      CO2 (VE/VCO2) at the anaerobic threshold (AT) were not associated with
      complications or length of stay. Greater absolute oxygen uptake at AT [VO2 at AT
      (L min(-1) )] was associated with early hospital discharge [OR 2.16 (95% CI 1.18
      3.96), P = 0.013] on multivariable analysis. CONCLUSIONS: When CPET is used to
      delineate perioperative management a low relative oxygen uptake [VO2 (ml kg(-1)
      min(-1) )] at the AT does not place patients at significantly higher risk of
      postoperative complications. This suggests CPET assessed "poor" fitness should
      not be used as a barrier to surgical intervention.

PMID- 24894659
TI  - Comparison and evaluation of three diagnostic methods for detection of beet curly
      top virus in sugar beet using different visualizing systems.
AB  - To diminish the time required for some diagnostic assays including polymerase
      chain reaction (PCR), loop-mediated isothermal amplification (LAMP; due to mainly
      DNA extraction step) and also triple antibody sandwich enzyme-linked
      immunosorbent assay (TAS-ELISA) into a minimum level, an innovative immunocapture
      LAMP (IC-LAMP) and immunocapture PCR (IC-PCR) protocol on the basis of beet curly
      top virus (BCTV) genome was used and optimized. TAS-ELISA was employed first to
      validate the existence of the virus. All six IC-LAMP primers (i.e. forward outer
      primer (F3), backward outer primer (B3), forward inner primer (FIP), backward
      inner primer (BIP), loop forward (LF) and loop backward (LB)) together with IC
      PCR primers were designed on the basis of the replication-associated protein
      (rep) gene (GenBank accession AF379637.1) of BCTV genome. Also, a novel
      colorimetric IC-LAMP assay for rapid and easy detection of BCTV was developed
      here, its potential compared with TAS-ELISA and IC-PCR assays. The method, on the
      whole, had the following advantages over the two mentioned procedures: (i)
      fascinatingly, no need of DNA extraction; (ii) no requirement of expensive and
      sophisticated tools for amplification and detection; (iii) no post-amplification
      treatment of the amplicons and (iv) a flexible and easy detection approach, which
      is visually detected by naked eyes using diverse visual dyes. 

PMID- 24894660
TI  - Enhancement of biogas production by co-digestion of potato pulp with cow manure
      in a CSTR system.
AB  - Anaerobic digestion (AD) process is a well-established method to generate energy
      from the organic wastes both from the environmental and economical perspectives.
      The purpose of present study is to evaluate energy production from potato wastes
      by incorporating cow manure into the process. Firstly, a laboratory pilot of one
      stage biogas production was designed and built according to continuously stirred
      tank reactor (CSTR) system. The setup was able to automatically control the
      environmental conditions of the process including temperature, duration, and rate
      of stirring. AD experiment was exclusively performed on co-digestion of potato
      peel (PP) and cow manure (CM) in three levels of mixing ratio including 20:80,
      50:50, 80:20 (PP:CM), and 0:100 as control treatment based on the volatile solid
      (VS) weight without adding initial inoculums. After hydraulic retention time
      (HRT) of 50 days on average 193, 256, 348, and 149 norm liter (LN) (kg VS)(-1),
      methane was produced for different mixing ratios, respectively. Statistical
      analysis shows that these gas productions are significantly different. The
      average energy was determined based on the produced methane which was about 2.8
      kWh (kg VS)(-1), implying a significant energy production potential. The average
      chemical oxygen demand (COD) removal of treatments was about 61%, showing that it
      can be leached significantly with high organic matter by the employed pilot. The
      energy efficiency of 92% of the process also showed the optimum control of the
      process by the pilot.

PMID- 24894658
TI  - Swallowed topical corticosteroids reduce the risk for long-lasting bolus
      impactions in eosinophilic esophagitis.
AB  - BACKGROUND: Long-lasting food impactions requiring endoscopic bolus removal occur
      frequently in patients with eosinophilic esophagitis (EoE) and harbor a risk for
      severe esophageal injuries. We evaluated whether treatment with swallowed topical
      corticosteroids is able to reduce the risk of occurrence of this complication.
      METHODS: We analyzed data from the Swiss EoE Cohort Study. Patients with yearly
      clinic visits, during which standardized assessment of symptoms, endoscopic,
      histologic, and laboratory findings was carried out, were included. RESULTS: A
      total of 206 patients (157 males) were analyzed. The median follow-up time was 5
      years with a total of 703 visits (mean 3.41 visits/patient). During the follow-up
      period, 33 patients (16 % of the cohort) experienced 42 impactions requiring
      endoscopic bolus removal. We evaluated the following factors regarding the
      outcome 'bolus impaction' by univariate logistic regression modeling: swallowed
      topical corticosteroid therapy (OR 0.503, 95%-CI 0.255-0.993, P = 0.048),
      presence of EoE symptoms (OR 1.150, 95%-CI 0.4668-2.835, P = 0.761), esophageal
      stricture (OR 2.832, 95%-CI 1.508-5.321, P = 0.001), peak eosinophil count >10
      eosinophils/HPF (OR 0.724, 95%-CI 0.324-1.621, P = 0.433), blood eosinophilia (OR
      1.532, 95%-CI 0.569-4.118, P = 0.398), and esophageal dilation (OR 1.852, 95%-CI
      1.034-3.755, P = 0.017). In the multivariate model, the following factors were
      significantly associated with bolus impaction: swallowed topical corticosteroid
      therapy (OR 0.411, 95%-CI 0.203-0.835, P = 0.014) and esophageal stricture (OR
      2.666, 95%-CI 1.259-5.645, P = 0.01). Increasing frequency of use of swallowed
      topical steroids was associated with a lower risk for bolus impactions.
      CONCLUSIONS: Treatment of EoE with swallowed topical corticosteroids
      significantly reduces the risk for long-lasting bolus impactions.

PMID- 24894661
TI  - Aspect ratio dependent cytotoxicity and antimicrobial properties of nanoclay.
AB  - Nanoclays may enter human body through various routes such as through the
      respiratory and gastrointestinal tract, skin, blood, etc. There is dearth of such
      studies evaluating the interaction of clay nanoparticles with human cells. In
      particular, the interaction of proteins and nucleic acids with nanoparticles of
      different aspect ratio remains a domain that is very poorly probed and
      understood. In the present study, we address the issue of cytotoxicity and
      antimicrobial attributes of two distinct nanoclay platelets namely, laponite
      (diameter = 25 nm and thickness = 1 nm) and montmorillonite (MMT, diameter = 300
      nm and thickness = 1 nm), having different aspect ratio (25:1 vs 300:1).
      Cytotoxicity was assessed in both prokatyotes: Escherichia coli, eukaryotes-human
      embryonic kidney (HEK), and cervical cancer SiHa cell lines, and a comparative
      size-based analysis of the toxicity were made at different exposure time points
      by MTT assay. The antimicrobial activity of the nanoclays was evaluated by disc
      diffusion method (Kirbey-Bauer protocol). Laponite exhibited maximum efficacy as
      an antimicrobial agent against E. coli. Comparatively smaller size laponite could
      preferentially enter the cells, leading to relatively wider or larger zone of
      inhibition. On contradictory; laponite showed 74.67 % survival while MMT showed
      89.02 % survival in eukaryotic cells at 0.00001 % (w/v) concentration. In
      summary, both MMT and laponite indicated cytotoxicity at 0.05 % concentration
      within 24 h of exposure on HEK and cervical cancer (SiHa) cell lines. The
      toxicity was possibly dependent on size, aspect ratio, and concentration. 

PMID- 24894662
TI  - Biofunctionalized gold nanoparticle-conducting polymer nanocomposite based
      bioelectrode for CRP detection.
AB  - An electrochemical impedance immunosensing method for the detection and
      quantification of C-reactive protein (alphaCRP) in phosphate buffered saline
      (PBS) is demonstrated. The protein antibody, Ab-alphaCRP, has been covalently
      immobilized on a platform comprising of electrochemically deposited 3
      mercaptopropionic acid-capped gold nanoparticles Au(MPA)-polypyrrole (PPy)
      nanocomposite film of controlled thickness onto an indium tin oxide-coated glass
      plate. The free carboxyl groups present on the nanocomposite film have been used
      to site-specifically immobilize the Ab-alphaCRP biomolecules through a stable
      acyl amino ester intermediate generated by N-(3-dimethylaminopropyl)-N'-ethyl
      carbodiimide hydrochloride and N-hydroxysuccinimide. The nanocomposite film was
      characterized by atomic force microscopy, high-resolution transmission electron
      microscopy, Fourier transform infrared spectroscopy, and electrochemical
      techniques. The bioelectrode was electrochemically analyzed using modified
      Randles circuit in terms of constant phase element (CPE), electron transfer
      resistance (R et), and Warburg impedance (Z w). The value of n, a CPE exponent
      used as a gauge of heterogeneity, for the Au-PPy nanocomposite film was found to
      be 0.56 which is indicative of a rather rough morphology and porous structure. A
      linear relationship between the increased ?R et values and the logarithmic value
      of protein antigen, Ag-alphaCRP, concentrations was found in the range of 10 ng
      to 10 MUg mL(-1) with a R et sensitivity of 46.27 Omega cm(2)/decade of [Ag
      alphaCRP] in PBS (pH 7.4). 

PMID- 24894663
TI  - The difficulty of measuring the measurable.

PMID- 24894664
TI  - Treatment-related risk factors for development of skin breakdown in subjects with
      acute respiratory failure undergoing noninvasive ventilation or CPAP.
AB  - BACKGROUND: Noninvasive ventilation (NIV) has been recognized as an effective
      strategy in preventing endotracheal intubation in subjects with acute respiratory
      failure (ARF). Some interface-related complications have also been recognized,
      such as skin breakdown (SB). The aim of this study was to determine the frequency
      of SB and identify potential treatment-related risk factors for its development
      in adults with ARF undergoing NIV or CPAP. METHODS: A cross-sectional study was
      conducted in a general hospital. Subjects were retrospectively enrolled in this
      study if they were > 18 y old and developed ARF caused by any condition in which
      NIV or CPAP was indicated for at least one application for a period longer than 2
      h. The outcomes were the prevalence of SB and the evaluation of related risk
      factors. Data were extracted from the electronic medical records. A stepwise
      forward logistic regression model was used to identify independent risk factors
      for SB development. RESULTS: A total of 375 subjects (160 males) met the
      inclusion criteria and were enrolled in the study. Fifty-four subjects (14.4%)
      developed SB. The mean number of applications of NIV or CPAP carried out for > 2
      h was higher in subjects with SB (7.1 +/- 13.3 h) than in those without SB (4.4
      +/- 13.3 h) (P = .03). Subjects with SB also presented a higher total duration of
      NIV use (44.6 +/- 118.5 h) compared with subjects without SB (21.8 +/- 45.5 h) (P
      = .01). Subjects who developed SB presented a higher use of oronasal mask (92.6%)
      compared with the group that did not (21.5%) (P < .001). CONCLUSIONS: In patients
      with ARF undergoing NIV or CPAP, oronasal mask use for > 26 h was independently
      associated with development of SB.

PMID- 24894665
TI  - CAP-miRSeq: a comprehensive analysis pipeline for microRNA sequencing data.
AB  - BACKGROUND: miRNAs play a key role in normal physiology and various diseases.
      miRNA profiling through next generation sequencing (miRNA-seq) has become the
      main platform for biological research and biomarker discovery. However, analyzing
      miRNA sequencing data is challenging as it needs significant amount of
      computational resources and bioinformatics expertise. Several web based
      analytical tools have been developed but they are limited to processing one or a
      pair of samples at time and are not suitable for a large scale study. Lack of
      flexibility and reliability of these web applications are also common issues.
      RESULTS: We developed a Comprehensive Analysis Pipeline for microRNA Sequencing
      data (CAP-miRSeq) that integrates read pre-processing, alignment,
      mature/precursor/novel miRNA detection and quantification, data visualization,
      variant detection in miRNA coding region, and more flexible differential
      expression analysis between experimental conditions. According to computational
      infrastructure, users can install the package locally or deploy it in Amazon
      Cloud to run samples sequentially or in parallel for a large number of samples
      for speedy analyses. In either case, summary and expression reports for all
      samples are generated for easier quality assessment and downstream analyses.
      Using well characterized data, we demonstrated the pipeline's superior
      performances, flexibility, and practical use in research and biomarker discovery.
      CONCLUSIONS: CAP-miRSeq is a powerful and flexible tool for users to process and
      analyze miRNA-seq data scalable from a few to hundreds of samples. The results
      are presented in the convenient way for investigators or analysts to conduct
      further investigation and discovery.

PMID- 24894667
TI  - Pathway model of parental help seeking for adolescents experiencing first-episode
      psychosis.
AB  - AIM: Parents and caregivers are confronted with many challenges when caring for
      adolescents experiencing first-episode psychosis (FEP). Understanding and support
      for parental help-seeking process is essential for adolescents' timely access to
      treatment. The study aimed to develop a pathway model of parental help seeking
      for adolescents experiencing FEP and identify crucial time points for
      intervention. METHODS: Directed content analysis was conducted on semi-structured
      qualitative interviews of 16 parents whose children had experienced FEP and
      focused on parents' experiences prior to and during FEP until first
      hospitalization. RESULTS: The resultant parental help seeking for FEP model
      included two stages and six phases. The contemplation stage is composed of phases
      of initial awareness, recognizing severity and considering options. The action
      stage entailed help-seeking intention, securing help and service appraisal. All
      parents promptly began help seeking after recognizing severe symptoms and sought
      advice from professional and community supports, although parents' lack of
      initial awareness was common. Further analysis on individual parents' help
      seeking trajectories showed that among the 50% parents who reported pre-existing
      childhood conditions, 87.5% did not report initial awareness of psychotic
      symptoms. CONCLUSIONS: Findings recommend intervention at three specific periods
      of help seeking. First, psychoeducation is needed when parents first engage with
      health care for their children's disabling conditions. Professionals treating
      childhood conditions need training to vigilantly monitor the overall mental
      health of the children over time. Second, it is important to enhance the roles of
      formal and informal community resources in facilitating parental help seeking.
      Finally, family-focused interventions are essential in supporting the family for
      securing needed treatment.

PMID- 24894666
TI  - Potential regenerative rehabilitation technology: implications of mechanical
      stimuli to tissue health.
AB  - BACKGROUND: Mechanical loads induced through muscle contraction, vibration, or
      compressive forces are thought to modulate tissue plasticity. With the emergence
      of regenerative medicine, there is a need to understand the optimal mechanical
      environment (vibration, load, or muscle force) that promotes cellular health. To
      our knowledge no mechanical system has been proposed to deliver these isolated
      mechanical stimuli in human tissue. We present the design, performance, and
      utilization of a new technology that may be used to study localized mechanical
      stimuli on human tissues. A servo-controlled vibration and limb loading system
      were developed and integrated into a single instrument to deliver vibration,
      compression, or muscle contractile loads to a single limb (tibia) in humans. The
      accuracy, repeatability, transmissibility, and safety of the mechanical delivery
      system were evaluated on eight individuals with spinal cord injury (SCI).
      FINDINGS: The limb loading system was linear, repeatable, and accurate to less
      than 5, 1, and 1 percent of full scale, respectively, and transmissibility was
      excellent. The between session tests on individuals with spinal cord injury (SCI)
      showed high intra-class correlations (>0.9). CONCLUSIONS: All tests supported
      that therapeutic loads can be delivered to a lower limb (tibia) in a safe,
      accurate, and measureable manner. Future collaborations between engineers and
      cellular physiologists will be important as research programs strive to determine
      the optimal mechanical environment for developing cells and tissues in humans.

PMID- 24894668
TI  - 'Sticking to a healthy diet is easier for me when I exercise regularly':
      cognitive transfer between physical exercise and healthy nutrition.
AB  - OBJECTIVE: Long-term rehabilitation success depends on regular exercise and
      healthy nutrition. The present study introduces a new framework to explain this
      association on a psychosocial level. The exercise-nutrition relationship was
      investigated by exploring the sequential mediation of habit strength and transfer
      cognitions. DESIGN: Analyses were performed at two measurement points in time (at
      12 and 18 months after rehabilitation), involving 470 medical rehabilitation
      patients who participated in an exercise intervention. MAIN OUTCOME MEASURES:
      Patients filled in paper-pencil questionnaires assessing exercise (t1) and habit
      strength, transfer cognitions and healthy nutrition at follow-up (t2). RESULTS:
      Habit strength and transfer cognitions mediated the relationship between exercise
      and nutrition. CONCLUSION: Findings suggest that habit strength and transfer
      cognitions are important factors underlying the relationship between exercise and
      nutrition.

PMID- 24894669
TI  - MTHFR gene polymorphism and risk of myeloid leukemia: a meta-analysis.
AB  - An increasing body of evidence has shown that the amino acid changes at position
      1298 might eliminate methylenetetrahydrofolate reductase (MTHFR) enzyme activity,
      leading to insufficient folic acid and subsequent human chromosome breakage.
      Epidemiological studies have linked MTHFR single-nucleotide polymorphism (SNP)
      rs1801131 to myeloid leukemia risk, with considerable discrepancy in their
      results. We therefore were prompted to clarify this issue by use of a meta
      analysis. The search terms were used to cover the possible reports in the
      MEDLINE, Web of Knowledge, and China National Knowledge Infrastructure (CNKI)
      databases. Odds ratios were estimated to assess the association of SNP rs1801131
      with myeloid leukemia risk. Statistical heterogeneity was detected using the Q
      statistic and I (2) metric. Subgroup analysis was performed by ethnicity,
      histological subtype, and Hardy-Weinberg equilibrium (HWE). This meta-analysis of
      eight publications with a total of 1,114 cases and 3,227 controls revealed no
      global association. Nor did the subgroup analysis according to histological
      subtype and HWE show any significant associations. However, Asian individuals who
      harbored the CC genotype were found to have 1.66-fold higher risk of myeloid
      leukemia (odds ratio, 1.66; 95 % confidence interval, 1.10 to 2.49; P h = 0.342;
      I (2) = 0.114). Our meta-analysis has presented evidence supporting a possible
      association between the CC genotype of MTHFR SNP rs1801131 and myeloid leukemia
      in Asian populations.

PMID- 24894671
TI  - Polymorphism in PHD1 gene and risk of non-small cell lung cancer in a Chinese
      population.
AB  - Hypoxia is a common phenomenon in the development of solid tumors, and hypoxia
      inducible factor 1 (HIF-1) plays a central role in coordinating the cellular
      response to hypoxia and in oxygen homeostasis. The prolyl hydrolase 1 (PHD1) is a
      key adjustment factor that mediates the HIF-1 degradation and relates with the
      process of tumorigenesis. Thus, polymorphism in PHD1 may affect cellular response
      to hypoxic conditions and associate with cancer susceptibility. We conducted a
      case-control study with 406 non-small cell lung cancer cases and 812 healthy
      controls matched on age and sex to examine the effect of rs10680577 polymorphism
      within the PHD1 promoter on non-small cell lung cancer (NSCLC) risk in a Chinese
      population. The genotype of rs10680577 polymorphism was detected by non
      denaturing polyacrylamide gel electrophoresis. The ins/del genotype of rs10680577
      was associated with significantly increased non-small cell lung cancer risk
      (ins/del vs. ins/ins: OR = 1.35, 95 % confidence interval (CI) 1.05-1.74, P =
      0.020; ins/del vs. ins/ins + del/del: OR = 1.34, 95 % CI = 1.04-1.72, P = 0.022).
      In addition, the association was more pronounced in the group of >60 years of
      age. rs10680577 polymorphism is associated with the risk of non-small cell lung
      cancer in a Chinese population. This is the first time to show that PHD1
      rs10680577 is associated NSCLC risk.

PMID- 24894670
TI  - Association of ABCB1, beta tubulin I, and III with multidrug resistance of
      MCF7/DOC subline from breast cancer cell line MCF7.
AB  - Docetaxel is a first-line chemotherapeutic agent for treating advanced breast
      cancer. The development of chemoresistance or multidrug resistance (MDR),
      however, results in breast cancer chemotherapy failure. This study aims to
      explore the molecular mechanisms underlying docetaxel-resistance in treatment of
      breast cancer. The docetaxel-resistant subline MCF7/DOC, derived from the
      parental sensitive breast cancer cell line MCF7, was established by intermittent
      exposure to moderate concentrations of docetaxel, followed by examination of its
      phenotypes. The MCF7/DOC subline showed cross resistance against paclitaxel,
      doxorubicin, methotrexate, and 5-Fu. Compared to the parental MCF7, MCF7/DOC
      cells were enlarged with heterogeneous sizes and a cobblestone and polygonal
      appearance. They were arrested at G2/M phase and proliferated slowly. The colony
      formation potential of MCF7/DOC in soft agar was significantly increased.
      MCF7/DOC cells showed reduced intracellular accumulation and increased efflux of
      rhodamine 123. The mRNA expression level of adenosine triphosphate binding
      cassette (ABC) transporter family, i.e., ABCB1, ABCC1, ABCC2, ABCG2, and beta
      tubulin isotypes were characterized by quantitative PCR. High-level expression of
      ABCB1, betaI, and betaIII tubulin mRNA in MCF7/DOC was detected. Downregulation
      of ABCB1, betaI, and betaIII tubulin mediated by three combined siRNAs resulted
      in stronger growth inhibition of MCF7/DOC than inhibition of the expression of
      individual genes. ABCB1, betaI, and betaIII tubulin might contribute to the MDR
      of MCF7/DOC and be potential therapeutic targets for overcoming MDR of breast
      cancer.

PMID- 24894672
TI  - CD24 single nucleotide polymorphisms and cancer risk.
AB  - Cluster of differentiation 24 (CD24) has been implicated in the development of
      cancer. Several single nucleotide polymorphisms (SNPs) in CD24 gene are reported
      to exert diverse effect on cancer risk. However, the association between CD24
      SNPs and cancer risk remains unclear due to contradictory published findings. We
      performed a meta-analysis by pooling all available published studies on the
      susceptibility of CD24 rs52812045 and rs3838646 polymorphisms to cancer. The
      pooled odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were
      calculated. There were five independent case-control studies with 5,539 cases and
      10,241 controls included into the present study. The pooled results showed that
      no appreciable relationship was identified between any of the SNPs of CD24 and
      cancer risk. Interestingly, a protective role of the CD24 rs3838646 polymorphism
      was found in the risk of breast cancer, but lack of statistical significance (del
      allele vs. TG allele: OR = 0.89; 95 % CI, 0.79-1.01; P OR = 0.063; del/del vs.
      TG/TG: OR = 0.70; 95 % CI, 0.44-1.12; P OR = 0.135; del/TG vs. TG/TG: OR = 0.91;
      95 % CI, 0.80-1.04, P OR = 0.180; del/del + del/TG vs. TG/TG: OR = 0.90; 95 % CI,
      0.79-1.03; P OR = 0.123; del/del vs. TG/TG + del/TG: OR = 0.69; 95 % CI, 0.44
      1.08, P OR = 0.105). Our study firstly provides the evidence that SNPs
      (rs52812045 and rs3838646) of CD24 may not modify the risk of cancer.
      Nonetheless, more individual studies with high quality are needed for further
      elucidation.

PMID- 24894673
TI  - Activated macrophages down-regulate expression of E-cadherin in hepatocellular
      carcinoma cells via NF-kappaB/Slug pathway.
AB  - Hepatocellular carcinomas are an aggressive malignancy mainly due to metastasis
      or postsurgical recurrence. Expression of E-cadherin is strongly reduced in
      Hepatocellular carcinoma (HCC) tissues, and its downregulation is connected to
      invasiveness and metastasis in hepatocellular carcinomas. The previous study
      showed that the supernatant from activated macrophages can downregulate the
      expression of E-cadherin in HCC cells. The partial known molecular mechanism is
      that tyrosine kinases c-Src- and EGFR phosphorylate beta-catenin and E-cadherin
      leading to destabilization of E-cadherin/beta-catenin complex. The aim of this
      study is to clarify other mechanism by which activated macrophages downregulate
      the expression of E-cadherin. We detect the expression of E-cadherin and
      macrophage infiltration in hepatocellular carcinoma tissues by double-staining
      immunohistochemistry and evaluate the relationship between macrophages and E
      cadherin expression in hepatocellular carcinoma cells in vitro experiments. We
      found that reduced expression of E-cadherin was associated with macrophage
      infiltration along the border between the tumor nest and stroma in hepatocellular
      carcinoma tissues. Besides, protein expression of E-cadherin was significantly
      decreased in hepatocellular carcinoma cells co-cultured with macrophages derived
      from THP-1 cells. Consistently, mRNA expression of E-cadherin was also decreased
      in cancer cells co-cultured with THP-1-differentiated macrophages. Moreover, the
      downregulation of E-cadherin expression was companied by upregulation of Slug
      expression in cancer cells with conditional medium from THP-1-differentiated
      macrophage culture. The change in expression of E-cadherin and Slug was abrogated
      when NF-kappaB signaling pathway was blocked. All the findings suggested that
      macrophages contributed to the decreased expression of E-cadherin by NF
      kappaB/Slug pathway in hepatocellular carcinomas.

PMID- 24894674
TI  - Decreased expression of IGFBP7 was a poor prognosis predictor for gastric cancer
      patients.
AB  - Increasing evidence indicated that insulin-like growth factor binding protein 7
      (IGFBP7) was regarded as a potential tumor suppressor in various human cancers,
      but its role in gastric cancer is still largely unknown. In the present study, we
      performed a retrospective study which includes 247 gastric cancer patients. Among
      them, the IGFBP7 expression was detected by qRT-PCR in 138 cases of gastric
      cancer and adjacent non-tumor tissues and was further correlated with the
      expression of p53, Ki-67, and the clinicopathologic features. The results
      indicated that both IGFBP7 mRNA and protein in gastric cancer tissues were
      significantly lower than those in the adjacent non-tumor tissues. Additionally,
      the expression of IGFBP7 was correlated with the depth of invasion, lymph node
      metastasis, and TNM stage. Interestingly, the expression of IGFBP7 was negatively
      associated with Ki-67 (r = -0.227, P < 0.001) but positively associated with p53
      (r = 0.140, P = 0.028). Univariate analysis showed that low expression of IGFBP7
      was associated with poor prognosis (P < 0.001), and multivariate analysis showed
      that IGFBP7 (HR = 1.87; 95 % CI 1.65-2.17), distant metastasis (HR = 2.68; 95 %
      CI 1.58-4.56), and tumor size (HR = 1.45; 95 % CI 0.90-2.32) were independent
      prognostic factors for gastric cancer patients. These results demonstrated that
      IGFBP7 was downregulated in gastric cancer, and its low expression was
      potentially correlated with increased cancer cell proliferation and could be used
      to predicate poor prognosis in these patients.

PMID- 24894675
TI  - ARMC8alpha promotes proliferation and invasion of non-small cell lung cancer
      cells by activating the canonical Wnt signaling pathway.
AB  - ARMC8 proteins are novel armadillo repeat containing proteins, which are well
      conserved in eukaryotes and are involved in a variety of processes such as cell
      migration, proliferation, tissue maintenance, signal transduction, and
      tumorigenesis. Armadillo repeat proteins include well-known proteins such as beta
      catenin and p120ctn. Our current knowledge of ARMC8, especially its role in
      cancer, is limited. In this study, we quantified ARMC8 expression in 112 non
      small cell lung cancer (NSCLC) tissues and adjacent non-cancerous tissues, and
      seven lung cancer cell lines using immunohistochemistry staining and Western
      blotting. ARMC8 level was significantly higher in NSCLC tissues than in the
      adjacent normal tissues (67.9 % versus 5.4 %, p < 0.05) and was significantly
      associated with TNM stage (p = 0.022), lymph node metastasis (p = 0.001), and
      poor prognosis (p < 0.001) in NSCLC patients. Cox regression analysis
      demonstrated that ARMC8 was an independent prognostic factor for NSCLC.
      Consistent with this, ARMC8alpha downregulation by siRNA knockdown inhibited
      growth, colony formation, and invasion in A549 lung cancer cells, while
      ARMC8alpha overexpression promoted growth, colony formation, and invasion in
      H1299 lung cancer cells. In addition, ARMC8alpha knockdown downregulated
      canonical Wnt-signaling pathway activity and cyclin D1 and matrix
      metalloproteinase (MMP)-7 expression. Consistent with this, ARMC8alpha
      overexpression upregulated canonical Wnt-signaling pathway activity and cyclin D1
      and MMP-7 expression. These results indicate that ARMC8alpha upregulates cyclin
      D1 and MMP7 expression by activating the canonical Wnt-signaling pathway and
      thereby promoting lung cancer cell proliferation and invasion. Therefore, ARMC8
      might serve as a novel therapeutic target in NSCLC.

PMID- 24894676
TI  - MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells.
AB  - MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in human cancers.
      Increasing evidence shows that deregulation of miRNAs contributes to the
      development and progression of human non-small cell lung cancer (NSCLC). Here, we
      identified miR-186 as a tumor suppressor in NSCLC, which was decreased in NSCLC.
      Overexpression of miR-186 significantly inhibited proliferation, migration, and
      invasion of NSCLC cells. In addition, Rho-associated protein kinase 1 (ROCK1) was
      identified as a target of miR-186 in NSCLC cells. Restoration of ROCK1 remarkably
      reversed the tumor-suppressive effects of miR-186 on cell proliferation,
      migration, and invasion in NSCLC cells. Furthermore, ROCK1 was inversely
      correlated with miR-186 expression in NSCLC. Collectively, our data indicate that
      miR-186 functions as tumor suppressor in NSCLC by targeting ROCK1. 

PMID- 24894677
TI  - Sneezing during drug-induced sedation endoscopy.

PMID- 24894678
TI  - Endothelial function is not always well preserved in obese patients with mild
      OSA.

PMID- 24894679
TI  - Sleep-disordered breathing-related neurocognitive impairment, time to think
      beyond hypoxia and sleep fragmentation?

PMID- 24894680
TI  - Diagnosis and treatment of snoring in adults--S2k guideline of the German Society
      of Otorhinolaryngology, Head and Neck Surgery.

PMID- 24894681
TI  - Semi-automated imaging of tissue-specific fluorescence in zebrafish embryos.
AB  - Zebrafish embryos are a powerful tool for large-scale screening of small
      molecules. Transgenic zebrafish that express fluorescent reporter proteins are
      frequently used to identify chemicals that modulate gene expression. Chemical
      screens that assay fluorescence in live zebrafish often rely on expensive,
      specialized equipment for high content screening. We describe a procedure using a
      standard epifluorescence microscope with a motorized stage to automatically image
      zebrafish embryos and detect tissue-specific fluorescence. Using transgenic
      zebrafish that report estrogen receptor activity via expression of GFP, we
      developed a semi-automated procedure to screen for estrogen receptor ligands that
      activate the reporter in a tissue-specific manner. In this video we describe
      procedures for arraying zebrafish embryos at 24-48 hours post fertilization (hpf)
      in a 96-well plate and adding small molecules that bind estrogen receptors. At 72
      96 hpf, images of each well from the entire plate are automatically collected and
      manually inspected for tissue-specific fluorescence. This protocol demonstrates
      the ability to detect estrogens that activate receptors in heart valves but not
      in liver. 

PMID- 24894683
TI  - Transplantation of human placenta-derived mesenchymal stem cells in a silk
      fibroin/hydroxyapatite scaffold improves bone repair in rabbits.
AB  - The main requirements for successful tissue engineering of the bone are non
      immunogenic cells with osteogenic potential and a porous biodegradable scaffold.
      The purpose of this study is to evaluate the potential of a silk
      fibroin/hydroxyapatite (SF/HA) porous material as a delivery vehicle for human
      placenta-derived mesenchymal stem cells (PMSCs) in a rabbit radius defect model.
      In this study, we randomly assigned 16 healthy adult New Zealand rabbits into two
      groups, subjected to transplantation with either SF/HA and PMSCs (experimental
      group) or SF/HA alone (control group). To evaluate fracture healing, we assessed
      the extent of graft absorption, the quantity of newly formed bone, and re
      canalization of the cavitas medullaris using radiographic and histological tools.
      We performed flow cytometric analysis to characterize PMSCs, and found that while
      they express CD90, CD105 and CD73, they stain negative for HLA-DR and the
      hematopoietic cell surface markers CD34 and CD45. When PMSCs were exposed to
      osteogenic induction medium, they secreted calcium crystals that were identified
      by von Kossa staining. Furthermore, when seeded on the surface of SF/HA scaffold,
      they actively secreted extracellular matrix components. Here, we show, through
      radiographic and histological analyses, that fracture healing in the experimental
      group is significantly improved over the control group. This strongly suggests
      that transplantation of human PMSCs grown in an SF/HA scaffold into injured
      radius segmental bone in rabbits, can markedly enhance tissue repair. Our finding
      provides evidence supporting the utility of human placenta as a potential source
      of stem cells for bone tissue engineering. 

PMID- 24894684
TI  - Antibacterial activities of Ligaria cuneifolia and Jodina rhombifolia leaf
      extracts against phytopathogenic and clinical bacteria.
AB  - Six plant extracts prepared from Ligaria cuneifolia and Jodina rhombifolia were
      screened for their potential antimicrobial activities against phytopathogens and
      clinically standard reference bacterial strains. Bioautography and broth
      microdilution methods were used to study samples antibacterial activities against
      7 bacterial strains. The minimum inhibitory concentrations (MICs) and minimum
      bactericidal concentrations (MBCs) of samples were attained. An antibacterial
      activity guided isolation and identification of active compounds was carried out
      for L. cuneifolia methanolic extract (LCME). Both methanolic and aqueous extracts
      from L. cuneifolia showed inhibitory activities against phytopathogenic bacteria,
      with MICs ranging from 2.5 to 156 MUg mL(-1) for LCME and 5 mg mL(-1) for the
      aqueous extract. None of the three J. rhombifolia extracts showed significant
      antibacterial activities against phytopathogenic strains (MIC > 5 mg mL(-1)),
      except for the aqueous extracts against Pseudomonas syringae (MIC = 312 MUg mL(
      1)). Only LCME showed bactericidal activities against phytopathogenic strains
      (MBCs = 78 MUg mL(-1)). The LCME exhibited significant inhibitory activity
      against reference clinical strains: Escherichia coli (MIC = 156 MUg mL(-1)) and
      Staphylococcus aureus (MIC = 78 MUg mL(-1), MBC = 312 MUg mL(-1)). LCME active
      compounds were identified as flavonol mono and diglycosides, and gallic acid. The
      antibacterial activity of purified compounds was also evaluated. A synergistic
      effect against S. aureus was found between gallic acid and a quercetin glycoside.
      Hence, anti-phytopathogenic bacteria potential compounds isolated from L.
      cuneifolia could be used as an effective source against bacterial diseases in
      plants. 

PMID- 24894686
TI  - Clinical alignment variations in total knee arthroplasty with different
      navigation methods.
AB  - BACKGROUND: We compared the resulting alignment in 90 degrees  of flexion and in
      full extension after total knee arthroplasty (TKA) with two navigation systems
      using different techniques: a measured resection (MR) system and a gap -
      balancing (GB) system. METHODS: Varus and valgus alignment in extension and
      flexion was compared in 100 consecutive patients who had TKA with an MR distal
      femoral-cut-first technique at one institution and 100 consecutive patients in
      whom a GB tibial-cut-first technique was used at another institution. Alignment
      deviation of three degrees or more from neutral was considered an outlier.
      RESULTS: No significant difference between the groups in coronal alignment in
      extension or flexion was found, but there were three times the number of outliers
      for clinical alignment in flexion for the MR group compared to the GB group.
      CONCLUSIONS: The use of the GB tibial-cut-first computer-assisted TKA navigation
      may provide a more consistent clinical alignment in flexion than systems using an
      MR technique. LEVEL OF EVIDENCE: Therapeutic study. Level 2.

PMID- 24894689
TI  - Mapping ICT access and disability in the workplace: An empirical study in Italy.
AB  - BACKGROUND: It is well known that the Information and Communication Technologies
      (ICT) are important to assist people with disability in the workplace. OBJECTIVE:
      In this context, this paper sheds light on the state of ICT accessibility for
      Italian employees with disabilities in private sector companies by mapping and
      critically analyzing the assistive role of ICT. METHODS: To do this, empirical
      evidence was drawn from a multi-methods research with middle and top managers
      from 97 medium and large Italian companies. Quantitative data was collected using
      a survey was directed at personnel identified as Human Resource (HR) and
      Information System (IS) managers, followed by a qualitative study with selected
      firms whose aim was to understand the inner workings of assistive technology and
      the decision making process related to assistive technology acquisition and use.
      RESULTS: The main results show the role and the integration level of people with
      disabilities, and the presence and effectiveness of specific assistive
      technologies. DISCUSSION: Ways to improve the inclusion of people with disability
      in the workplace, as well as the use of assistive technologies are discussed.
      CONCLUSION: ICT could be more disseminated within companies and best used with
      modifications to improve usability.

PMID- 24894687
TI  - Effect of a worktable position on head and shoulder posture and shoulder muscles
      in manual material handling.
AB  - BACKGROUND: According to a recent research, manual working with high levels of
      static contraction, repetitive loads, or extreme working postures involving the
      neck and shoulder muscles causes an increased risk of neck and shoulder
      musculoskeletal disorders. OBJECTIVE: We investigated the effects of the
      forwardly worktable position on head and shoulder angles and shoulder muscle
      activity in manual material handling tasks. METHODS: The forward head and
      shoulder angles and the activity of upper trapezius, levator scapulae, and middle
      deltoid muscle activities of 15 workers were measured during performing of manual
      material handling in two tasks that required different forward head and shoulder
      angles. RESULTS: The second manual material task required a significantly
      increased forward head and shoulder angle. The upper trapezius and levator
      scapulae muscle activity in second manual material task was increased
      significantly compared with first manual material task. The middle deltoid muscle
      activity in second manual material task was not significantly different compared
      with first manual material task. CONCLUSIONS: Based on this result, the forward
      head and shoulder angles while performing manual work need to be considered in
      selection of the forward distance of a worktable form the body. The high level
      contractions of the neck and shoulder muscles correlated with neck and shoulder
      pain. Therefore, the forward distance of a worktable can be an important factor
      in preventing neck and shoulder pain in manual material handling workers.

PMID- 24894690
TI  - Work life after psychosis: A detailed examination.
AB  - BACKGROUND: Conducting research on the work outcomes of first episode psychosis
      (FEP) samples may extend our understanding of the factors associated with the
      work outcome of people with schizophrenia and other psychotic illnesses.
      OBJECTIVE: To conduct a detailed study of the work outcome of an FEP sample.
      METHODS: Members of a FEP cohort, who had completed a 12-year clinical outcome
      assessment, were invited to participate in an adjunctive work outcome study.
      Engagement in paid and non-paid work was first established and the relationship
      with potentially influential baseline characteristics investigated. Subsequently
      the influence of work outcome to participants' level of quality of life, mental
      health, recovery, and social inclusion were examined. RESULTS: Among the 38
      participants the mean percentage of time spent in work was 62% of which 50% was
      in paid work and 12% was in non-paid work. Being employed at inception was the
      only independent predictor of the duration of the follow-up period spent in work.
      Relationships between work outcome and all measures of wellbeing were found.
      CONCLUSION: The paid and non-paid work attained by people affected by a psychotic
      illness played an important role in the extent of their wellbeing, recovery, and
      social inclusion.

PMID- 24894692
TI  - Staff perceptions of workplace violence in a pediatric emergency department.
AB  - BACKGROUND: A teenage patient with an undiscovered gun in a pediatric emergency
      department (ED) created risk for violence and high staff stress. OBJECTIVE: To
      describe ED staff views of workplace violence risk to guide improvements and
      address staff fears. PARTICIPANTS: Two hundred thirty four health care staff in a
      Midwestern pediatric hospital system including ED and urgent care locations.
      METHODS: An electronic survey gathered staff perceptions of workplace safety via
      multiple choice, forced rank, and narrative responses. Frequency of concern and
      fear for personal safety from patient or visitor violence was calculated. Events
      causing fear, and perceptions about presence of local police and hospital
      security staff, were examined. RESULTS: 26% of staff expressed concern for safety
      at least weekly. Twenty seven percent experienced situations causing fear at
      least monthly. Primary causes of fear were patient or visitor agitation (with
      violence potential) and weapons in the ED. Respondents would feel ''more safe''
      with increased presence from hospital security staff (55%) and local police
      (71%). CONCLUSIONS: Workplace violence occurs in pediatric emergency departments.
      Both real and perceived threats must be addressed for staff wellbeing.
      Utilization of staff perception of risk and improvement ideas is a valuable
      strategy to guide violence reduction at work.

PMID- 24894693
TI  - Minireview: Peptide analogs and short sequence oligopeptides as modulators of
      skin pigmentation.
AB  - Short sequence amino acids or oligopeptides have recently garnered attention for
      use as treatments for a myriad of dermatologic disorders due to their ability to
      effect and modulate various biological processes in the epidermis and dermis,
      rendering them promising candidates as medical and cosmeceutical therapeutics.
      Major advantages include their relative ease of synthesis and multitude of
      modifications that can be applied to enhance potency, affinity, specificity,
      hydrophilicity or hydrophobicity and cytotoxicity. Given the photoprotective
      effects of eumelanin on skin, there has been substantial interest in developing
      agents, particularly alpha-MSH analogs, that can induce 'sunless tanning' helping
      reduce risk of melanoma and non-melanoma skin cancer. In this mini review, we
      present some of the recent and leading peptide modulators of melanogenesis with
      relevant clinical data and medical indications. Short sequence oligopeptides with
      tyrosinase inhibitory activity that can significantly reduce hyperpigmentation,
      as well alpha-MSH analogs that can enhance eumelanogenesis, are currently being
      clinically tested for treatment of erythropoietic protoporphyria, polymorphous
      light eruption, solar urticaria, actinic keratosis, and "sunless tanning".
      Success in developing such products can help reduce the incidence of skin cancer,
      one that surpasses that of all other human cancers combined. 

PMID- 24894691
TI  - Incidence and risk factors of workplace violence on psychiatric staff.
AB  - BACKGROUND: A study by Hesketh et al. found that 20% of psychiatric nurses were
      physically assaulted, 43% were threatened with physical assault, and 55% were
      verbally assaulted at least once during the equivalent of a single work week.
      From 2005 through 2009, the U.S. Department of Justice reported that mental
      health occupations had the second highest average annual rate of workplace
      violence, 21 violent crimes per 1,000 employed persons aged 16 or older.
      OBJECTIVE: An evaluation of risk factors associated with patient aggression
      towards nursing staff at eight locked psychiatric units. PARTICIPANTS: Two
      hundred eighty-four nurses in eight acute locked psychiatric units of the
      Veterans Health Administration throughout the United States between September
      2007 and September 2010. METHODS: Rates were calculated by dividing the number of
      incidents by the total number of hours worked by all nurses, then multiplying by
      40 (units of incidents per nurse per 40-hour work week). Risk factors associated
      with these rates were analyzed using generalized estimating equations with a
      Poisson model. RESULTS: Combining the data across all hospitals and weeks, the
      overall rate was 0.60 for verbal aggression incidents and 0.19 for physical
      aggression, per nurse per week. For physical incidents, the evening shift (3 pm -
      11 pm) demonstrated a significantly higher rate of aggression than the day shift
      (7 am - 3 pm). Weeks that had a case-mix with a higher percentage of patients
      with personality disorders were significantly associated with a higher risk of
      verbal and physical aggression. CONCLUSION: Healthcare workers in psychiatric
      settings are at high risk for aggression from patients.

PMID- 24894694
TI  - Flame experiments at the advanced light source: new insights into soot formation
      processes.
AB  - The following experimental protocols and the accompanying video are concerned
      with the flame experiments that are performed at the Chemical Dynamics Beamline
      of the Advanced Light Source (ALS) of the Lawrence Berkeley National Laboratory(1
      4). This video demonstrates how the complex chemical structures of laboratory
      based model flames are analyzed using flame-sampling mass spectrometry with
      tunable synchrotron-generated vacuum-ultraviolet (VUV) radiation. This
      experimental approach combines isomer-resolving capabilities with high
      sensitivity and a large dynamic range(5,6). The first part of the video describes
      experiments involving burner-stabilized, reduced-pressure (20-80 mbar) laminar
      premixed flames. A small hydrocarbon fuel was used for the selected flame to
      demonstrate the general experimental approach. It is shown how species' profiles
      are acquired as a function of distance from the burner surface and how the
      tunability of the VUV photon energy is used advantageously to identify many
      combustion intermediates based on their ionization energies. For example, this
      technique has been used to study gas-phase aspects of the soot-formation
      processes, and the video shows how the resonance-stabilized radicals, such as
      C3H3, C3H5, and i-C4H5, are identified as important intermediates(7). The work
      has been focused on soot formation processes, and, from the chemical point of
      view, this process is very intriguing because chemical structures containing
      millions of carbon atoms are assembled from a fuel molecule possessing only a few
      carbon atoms in just milliseconds. The second part of the video highlights a new
      experiment, in which an opposed-flow diffusion flame and synchrotron-based
      aerosol mass spectrometry are used to study the chemical composition of the
      combustion-generated soot particles(4). The experimental results indicate that
      the widely accepted H-abstraction-C2H2-addition (HACA) mechanism is not the sole
      molecular growth process responsible for the formation of the observed large
      polycyclic aromatic hydrocarbons (PAHs). 

PMID- 24894695
TI  - Strawberry ellagitannins thwarted the positive effects of dietary
      fructooligosaccharides in rat cecum.
AB  - Forty-eight male Wistar rats were fed diets containing low (0.051% of diet) or
      high (0.153% of diet) levels of an ellagitannin-rich (ET) strawberry extract with
      dietary fructooligosaccharides (FOS) or cellulose (CEL) for 4 weeks. The in vivo
      study demonstrated that some positive changes in the cecal metabolism resulting
      from the ingestion of a diet enriched only with FOS were completely or slightly
      suppressed by the dietary ET. In particular, the pH value (7.21 vs 7.36), short
      chain fatty acid production (41.2 vs 30.0 MUmol/100g BW), and beta-glucuronidase
      activity (20.2 vs 15.7 MUmol/h/g) in the cecum of rats fed with FOS were affected
      upon the addition of the ET extract. Dietary FOS caused higher metabolism of the
      tested ET strawberry extract in the gastrointestinal tract of rats. Moreover, the
      systemic effect of the supplements when consumed together showed undesired serum
      HDL-cholesterol decrease (0.78 vs 1.02 mmol/L in the treatment with FOS only). 

PMID- 24894696
TI  - CT for evaluation of potential renal donors - how does iterative reconstruction
      influence image quality and dose?
AB  - PURPOSE: To assess ASIR (adaptive statistical iterative reconstruction) technique
      regarding dose reduction and its impact on image quality in evaluation CTs of
      potential kidney donors. MATERIALS AND METHODS: Between May and November 2013, a
      prospective study of 53 assumingly healthy potential kidney donors was conducted.
      The subjects underwent abdominal evaluation CT prior to the planned explantation
      of a kidney and were randomly divided into 2 groups: Group A was examined with an
      ASIR 40 protocol (n=26), group B (n=27) was examined using a standard FBP
      (filtered back projection) protocol. Image quality was assessed both
      quantitatively (by obtaining attenuation values in different organ regions and
      calculating SNR and CNRs) and qualitatively (by two observers who evaluated image
      quality using a 5-point scale system). Applied dose was analyzed as CTDIvol
      (mGy), total DLP (mGy*cm) and effective dose (mSv). RESULTS: Applied dose in
      group A was about 26% lower than in group B (p<0.05). Between both groups, dose
      determining parameters such as scan length and patients' body diameter showed no
      significant difference. SNR (signal-to-noise ratio) was significantly higher in
      group A (p<0.05). CNRs (contrast-to-noise ratios) for different tissues were not
      significantly different. Observer rated image quality showed no significant
      difference. CONCLUSION: ASIR can contribute to a relevant dose reduction without
      any loss of image quality in CT scans for evaluating potential kidney donors.

PMID- 24894685
TI  - Angiotensin-converting enzyme inhibitor usage and acute kidney injury: a
      secondary analysis of RENAL study outcomes.
AB  - AIM: Acute kidney injury (AKI) is associated with increased mortality. While
      angiotensin-converting enzyme inhibitors (ACEI) are known to slow progression of
      chronic kidney disease, their role in AKI remains unclear. METHODS: The
      Randomised Evaluation of Normal vs. Augmented Level Replacement Therapy (RENAL)
      study data were analysed according to ACEI use over time. The primary outcome was
      all-cause mortality at 90 days following randomisation. Analyses used a
      multivariate Cox model adjusted for either baseline or for time-dependent
      covariates, and a sensitivity analysis of patients surviving to at least the
      median time to ACEI initiation. RESULTS: Of the 1463 participants with available
      data on ACE inhibitors usage, 142 (9.7%) received ACEI at least once during study
      data collection. Participants treated with ACEI were older (P = 0.02) and had
      less sepsis at baseline (P < 0.001). ACEI use was significantly associated with
      lower mortality at 90 days (HR 0.46, 95% CI 0.30-0.71, P < 0.001), and an
      increase in renal replacement therapy-free days (P < 0.001), intensive care unit
      free days (P < 0.001) and hospital free-days (P < 0.001) after adjusting for
      baseline covariates. Using the time-dependent analysis, however, the effect of
      ACEI administration was not significant (HR 0.78, 95% CI 0.51-1.21, P = 0.3). The
      sensitivity analysis in day 8 survivors produced similar results. CONCLUSION: In
      the RENAL study cohort, the use of ACEI during the study was not common and,
      after adjustment for time-dependent covariates, was not significantly associated
      with reductions in mortality. Further assessment of the effect of ACEI use in AKI
      patients is needed.

PMID- 24894697
TI  - Positive enhancement integral values in dynamic contrast enhanced magnetic
      resonance imaging of breast carcinoma: ductal carcinoma in situ vs. invasive
      ductal carcinoma.
AB  - OBJECTIVES: The aim of this study was to contribute to the standardization of the
      numeric positive enhancement integral (PEI) values in breast parenchyma, ductal
      carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the
      significance of the difference in PEI values between IDC and parenchyma, DCIS and
      parenchyma and IDC and DCIS. MATERIALS AND METHODS: In the prospective trial, we
      analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60
      consecutive patients with histologically confirmed unilateral DCIS (n=30) and IDC
      (n=30) and defined the PEI values (range; mean +/- SD) for the lesions and the
      breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and
      IDC and compared. PEI color maps (PEICM) were created. The differences in PEI
      values between IDC and parenchyma and between DCIS and parenchyma were tested
      according to t-test. Analysis of variance (ANOVA) was used to test the
      differences between the mean PEI values of parenchyma, DCIS and IDC. RESULTS: IDC
      showed highly statistically different PEI numeric values compared to breast
      parenchyma (748.7 +/- 32.2 vs. 74.6 +/- 17.0; p<0.0001). The same applied to the
      differences in the group of patients with DCIS (428.0 +/- 25.0 vs. 66.0 +/- 10.6;
      p<0.0001). The difference between IDC, DCIS and parenchyma were also considered
      highly statistically significant (p<0.0001) and so were the T/NT ratios for IDC
      and DCIS (10.1 +/- 2.4 vs. 6.6 +/- 1.4; p<0.0001). CONCLUSIONS: PEI numeric
      values may contribute to differentiation between invasive and in situ breast
      carcinoma.

PMID- 24894698
TI  - Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a
      pilot study.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system. Autoimmune inflammation is common in the early stages of MS. This
      stage is followed by the neurodegenerative process. The result of these changes
      is axon and myelin breakdown. Although MS is according to McDonald's revised
      diagnostic criteria primarily a clinical diagnosis, paraclinical investigation
      methods are an important part in the diagnosis of MS. In common practice,
      magnetic resonance imaging of the brain and spinal cord, examination of
      cerebrospinal fluid (CSF) and examination of visual evoked potentials are used.
      There are an increasing number of studies dealing with biomarkers in CSF and
      their role in the diagnosis and treatment of MS. We hypothesized that the levels
      of some markers could be changed in MS in comparison with controls. We studied
      five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10
      (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory
      markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's
      revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of
      beta-2-microglobulin and interleukin-8 in CSF were found to be significantly
      higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No
      differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels
      of all markers between both groups were found. The levels of two studied
      inflammatory markers were found to be increased at the time of first clinical
      symptoms of MS. Research on the role of inflammatory and neurodegenerative
      markers in MS should continue.

PMID- 24894700
TI  - Cardiovascular remodeling during long-term nocturnal home hemodialysis.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and
      mortality in patients with kidney failure. Nocturnal home hemodialysis (NHD) is a
      form of kidney replacement therapy whereby hemodialysis is performed for at least
      6-h overnight, at least 4 days per week. Little is known about the effects of NHD
      on cardiovascular remodeling as assessed by transthoracic echocardiography (TTE)
      and cardiac magnetic resonance imaging (CMR). OBJECTIVES: The primary objective
      of the study was to determine the long-term effects of NHD on cardiovascular
      remodeling using different imaging modalities over a one-year follow-up. METHODS
      AND RESULTS: A total of 11 patients were included in the study (6 males, mean age
      48 +/- 16 years) between 2009 and 2011 inclusive at a single tertiary care
      center. All patients underwent TTE and CMR at baseline and after 1 year of NHD.
      Left ventricular mass index decreased significantly at 1 year by both TTE (152 +/
      7-129 +/- 8 g/m(2), p < 0.05) and CMR (162 +/- 4-124 +/- 4 g/m(2), p < 0.05).
      There was also a significant decrease in both left and right atrial volume as
      well as in right ventricular mass index over 1 year of follow-up. Diastolic
      dysfunction, graded from 0 to 4, improved from a baseline grade of 3.4 to 1.2 at
      1-year follow-up. CONCLUSIONS: Long-term nocturnal hemodialysis leads to
      favorable cardiovascular remodeling with a reduction in cavity dimensions,
      regression of left ventricular hypertrophy, and an improvement in diastolic
      function, as assessed by both TTE and CMR.

PMID- 24894699
TI  - Inter-hemispheric EEG coherence analysis in Parkinson's disease: assessing brain
      activity during emotion processing.
AB  - Parkinson's disease (PD) is not only characterized by its prominent motor
      symptoms but also associated with disturbances in cognitive and emotional
      functioning. The objective of the present study was to investigate the influence
      of emotion processing on inter-hemispheric electroencephalography (EEG) coherence
      in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise,
      and disgust) were presented to 20 PD patients and 30 age-, education level-, and
      gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric
      coherence was computed from seven homologous EEG electrode pairs (AF3-AF4, F7-F8,
      F3-F4, FC5-FC6, T7-T8, P7-P8, and O1-O2) for delta, theta, alpha, beta, and gamma
      frequency bands. In addition, subjective ratings were obtained for a
      representative of emotional stimuli. Interhemispherically, PD patients showed
      significantly lower coherence in theta, alpha, beta, and gamma frequency bands
      than HC during emotion processing. No significant changes were found in the delta
      frequency band coherence. We also found that PD patients were more impaired in
      recognizing negative emotions (sadness, fear, anger, and disgust) than relatively
      positive emotions (happiness and surprise). Behaviorally, PD patients did not
      show impairment in emotion recognition as measured by subjective ratings. These
      findings suggest that PD patients may have an impairment of inter-hemispheric
      functional connectivity (i.e., a decline in cortical connectivity) during emotion
      processing. This study may increase the awareness of EEG emotional response
      studies in clinical practice to uncover potential neurophysiologic abnormalities.

PMID- 24894701
TI  - Treatment with a nicotine vaccine does not lead to changes in brain activity
      during smoking cue exposure or a working memory task.
AB  - AIMS: To assess whether immunization attenuates nicotinic stimulation of the
      brain and elucidate brain and behavioural responses during exposure to smoking
      cues and a working memory task. DESIGN: Randomized, placebo-controlled parallel
      group, repeated-measures design. SETTING: Maastricht University, the Netherlands.
      PARTICIPANTS: Forty-eight male smokers were randomized to receive five injections
      with either 400 MUg/ml of the 3'-aminomethylnicotine Pseudomonas aeruginosa r
      Exoprotein-conjugated vaccine or placebo. Subjects were tested on two occasions,
      once after a nicotine challenge and once after a placebo challenge, and were
      asked to refrain from smoking 10 hours before testing. MEASUREMENTS: Reaction
      times and accuracies were recorded during an n-back task. Moreover, regional
      blood oxygenated level-dependent (BOLD) response was measured during this task
      and during smoking cue exposure. FINDINGS: Greater activation was found in
      response to smoking cues compared to neutral cues in bilateral trans-occipital
      sulcus (P < 0.005); however, this effect did not survive correction for multiple
      comparisons. There was no difference in brain activity to smoking cues between
      the treatment groups and no effects of acute nicotine challenge were established.
      For the n-back task we found working memory load-sensitive increases in brain
      activity in several frontal and parietal areas (P < 0.0025). However, no effects
      of immunization or nicotine challenge were observed. CONCLUSION: No significant
      effects of immunization on brain activity in response to a nicotine challenge
      were established. Therefore this vaccine is not likely to be an effective aid in
      smoking cessation.

PMID- 24894702
TI  - Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor
      cells in primary breast cancer patients.
AB  - BACKGROUND: An imbalance between cell proliferation and programmed cell death can
      result in tumor growth. Although most systemic cytotoxic agents induce apoptosis
      in tumor cells, a high apoptotic rate in primary breast cancer correlates with
      poor prognosis. The aim of this study was to investigate the incidence and the
      prognostic significance of apoptotic disseminated tumor cells (DTC) in the bone
      marrow (BM) of breast cancer patients who either underwent primary surgery or
      primary systemic chemotherapy (PST). METHODS: A total of 383 primary breast
      cancer patients with viable DTC in the BM were included into this study. Eighty
      five patients were initially treated with primary systemic chemotherapy whereas
      298 patients underwent surgery first. Detection of apoptotic DTC were performed
      by immunocytochemistry using the M30 antibody which detects a neo-epitope
      expressed after caspase cleavage of cytokeratin 18 during early apoptosis. The
      median follow up was 44 months (range 10-88 months). RESULTS: Eighty-two of 298
      (27%) primary operated patients and 41 of 85 (48%) patients treated with primary
      systemic systemic therapy had additional apoptotic DTC (M30 positive). In the
      neoadjuvant group M30-positive patients were less likely to suffer relapse than
      those without apoptotic DTC (7% vs. 23% of the events, p=0.049). In contrast, the
      detection of apoptotic DTC in patients treated by primary surgery was
      significantly associated with poor overall survival (5% vs. 12% of the events,
      p=0.008). CONCLUSIONS: Apoptotic DTC can be detected in breast cancer patients
      before and after systemic treatment. The presence of apoptotic DTC in patients
      with PST may be induced by the cytotoxic agents. Thus, both spontaneous and
      chemotherapy-induced apoptosis may have different prognostic significance.

PMID- 24894703
TI  - Phase separation and self-assembly of colloidal dimers with tunable attractive
      strength: from symmetrical square-wells to Janus dumbbells.
AB  - We numerically investigate colloidal dimers with asymmetric interaction strengths
      to study how the interplay between molecular geometry, excluded volume effects
      and attractive forces determines the overall phase behavior of such systems.
      Specifically, our model is constituted by two rigidly-connected tangent hard
      spheres interacting with other particles in the first instance via identical
      square-well attractions. Then, one of the square-well interactions is
      progressively weakened, until only the corresponding bare hard-core repulsion
      survives, giving rise to a "Janus dumbbell" model. We investigate structure,
      thermodynamics and phase behavior of the model by means of successive umbrella
      sampling and Monte Carlo simulations. In most of the cases, the system behaves as
      a standard simple fluid, characterized by a gas-liquid phase separation, for
      sufficiently low temperatures. In these conditions we observe a remarkable linear
      scaling of the critical temperature as a function of the interaction strength.
      But, as the interaction potential approaches the Janus dumbbell limit, we observe
      the spontaneous formation of self-assembled lamellar structures, preempting the
      gas-liquid phase separation. Comparison with previous studies allows us to
      pinpoint the role of the interaction range in controlling the onset of ordered
      structures and the competition between the formation of these structures and gas
      liquid condensation. 

PMID- 24894705
TI  - Identification method for digital image forgery and filtering region through
      interpolation.
AB  - Because of the rapidly increasing use of digital composite images, recent studies
      have identified digital forgery and filtering regions. This research has shown
      that interpolation, which is used to edit digital images, is an effective way to
      analyze digital images for composite regions. Interpolation is widely used to
      adjust the size of the image of a composite target, making the composite image
      seem natural by rotating or deforming. As a result, many algorithms have been
      developed to identify composite regions by detecting a trace of interpolation.
      However, many limitations have been found in detection maps developed to identify
      composite regions. In this study, we analyze the pixel patterns of
      noninterpolation and interpolation regions. We propose a detection map algorithm
      to separate the two regions. To identify composite regions, we have developed an
      improved algorithm using minimum filer, Laplacian operation and maximum filters.
      Finally, filtering regions that used the interpolation operation are analyzed
      using the proposed algorithm. 

PMID- 24894706
TI  - Durable modification of segmented polyurethane for elastic blood-contacting
      devices by graft-type 2-methacryloyloxyethyl phosphorylcholine copolymer.
AB  - We propose a novel application of 2-methacryloyloxyethyl phosphorylcholine (MPC)
      polymers for enhancing the performance of modified segmented polyurethane (SPU)
      surfaces for the development of a small-diameter vascular prosthesis. The SPU
      membranes were modified by random-type, block-type, and graft-type MPC polymers
      that were prepared using a double-solution casting procedure on stainless steel
      substrates. Among these MPC polymers, the graft-type poly(MPC-graft-2-ethylhexyl
      methacrylate [EHMA]), which is composed of a poly(MPC) segment as the main chain
      and poly(EHMA) segments as side chains, indicated a higher stability on the SPU
      membrane after being peeled off from the stainless steel substrate, as well as
      after immersion in an aqueous medium. This stability was caused by the
      intermiscibility in the domain of the poly(EHMA) segments and the soft segments
      of the SPU membrane. Each SPU/MPC polymer membrane exhibited a dramatic
      suppression of protein adsorption from human plasma and endothelium cell
      adhesion. Based on these results, the performance of SPU/poly(MPC-graft-EHMA)
      tubings 2 mm in diameter as vascular prostheses was investigated. Even after
      blood was passed through the tubings for 2 min, the graft-type MPC polymers
      effectively protected the blood-contacting surfaces from thrombus formation. In
      summary, SPU modified by graft-type MPC polymers has the potential for practical
      application in the form of a non-endothelium, small-diameter vascular prosthesis.

PMID- 24894704
TI  - Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for
      the expression of inhibitory LTP.
AB  - Postsynaptic long-term potentiation of inhibition (iLTP) can rely on increased
      GABAA receptors (GABA(A)Rs) at synapses by promoted exocytosis. However, the
      molecular mechanisms that enhance the clustering of postsynaptic GABA(A)Rs during
      iLTP remain obscure. Here we demonstrate that during chemically induced iLTP
      (chem-iLTP), GABA(A)Rs are immobilized and confined at synapses, as revealed by
      single-particle tracking of individual GABA(A)Rs in cultured hippocampal neurons.
      Chem-iLTP expression requires synaptic recruitment of the scaffold protein
      gephyrin from extrasynaptic areas, which in turn is promoted by CaMKII-dependent
      phosphorylation of GABA(A)R-beta3-Ser(383). Impairment of gephyrin assembly
      prevents chem-iLTP and, in parallel, blocks the accumulation and immobilization
      of GABA(A)Rs at synapses. Importantly, an increase of gephyrin and GABA(A)R
      similar to those observed during chem-iLTP in cultures were found in the rat
      visual cortex following an experience-dependent plasticity protocol that
      potentiates inhibitory transmission in vivo. Thus, phospho-GABA(A)R-beta3
      dependent accumulation of gephyrin at synapses and receptor immobilization are
      crucial for iLTP expression and are likely to modulate network excitability.

PMID- 24894707
TI  - ALT chimeric flap associated to a dura mater biomatrix substitute for severe
      desfigurative mandible osteoradionecrosis and deficient bone consolidation after
      a free fibula flap.

PMID- 24894708
TI  - New horizontal v-shaped osteotomy for correction of protrusion of the zygoma and
      the zygomatic arch in East Asians: indication and results.
AB  - Protrusion of the zygoma is commonly considered undesirable and unattractive
      among East-Asians, and many try to achieve a harmonious oval midface by having
      various cosmetic operations. However, effective contouring for a severe
      protruding zygoma has rarely been reported .The objectives of this study
      therefore were to investigate the feasibility and effectiveness of a horizontal V
      shaped ostectomy for correction of protrusion of the zygoma and zygomatic arch,
      and to discuss its indications. From January 2008 to December 2011 we treated 27
      patients by contouring of the zygoma with a horizontal V-shaped ostectomy through
      intraoral and preauricular incisions. The effectiveness was then evaluated with
      cephalometric radiographs, 3-dimensional computed tomography, and standard facial
      photographs taken before and after operation. The postoperative appearance of all
      27 patients showed that the protrusion had been effectively reduced with no
      serious complications, and the facial contour had improved. The final aesthetic
      outcomes were satisfactory for both surgeons and patients. The horizontal V
      shaped osteotomy is a good technique for the reduction of protrusion of the
      zygoma and zygomatic arch, and it has the advantages of more convenient
      multishifting, better results, and fewer complications. It also ensures the
      integrity of the structure of the malar complex. 

PMID- 24894709
TI  - Sialoendoscopy: a viable treatment for I(131) induced sialoadenitis.
AB  - To evaluate the viability, efficacy, and safety of sialoendoscopy for the
      diagnosis and management of radioiodine I(131-) related sialoadenitis, we
      retrospectively reviewed 30 patients referred between September 2007 and July
      2013 from the Thyroid Surgery Unit to the Maxillofacial Unit of the Second
      University of Naples Hospital with persistent sialoadenitis after treatment with
      I(131). After the affected gland had been isolated, the endoscope was introduced
      into the duct under local anaesthesia with 2% lignocaine and continuous lavage
      with isotonic saline, and was advanced until it reached the ductal system. We
      studied 24 women and 6 men, mean (SD) age 52 (??) years. In 25 patients I(131)
      was given for papillary (83%), in 3 for medullary (10%), and in 2 for follicular
      thyroid carcinoma (7%). Stenosis alone was found in 30 glands (40%), mucous plugs
      alone in 35 (47%), and mucous plugs, stenosis, and kinks in 10 (13%). Of the 75
      glands, dilatation of the ducts was successful in 70, and we completely removed
      all mucous plugs and kinks. We achieved symptomatic improvement in 23 patients
      (77%) during a follow-up ranging from 2 weeks to 84 months. Sialoendoscopy is a
      viable technique for the diagnosis of obstructive salivary disease, and is a safe
      and effective way to treat sialoadenitis, the most common complication of
      treatment with I(131).

PMID- 24894710
TI  - Open wound healing of the osseocutaneous fibula flap donor site.
AB  - Split skin grafts are the predominant method of closure for fibular flap donor
      sites. We present a novel approach to manage the donor site using the inter
      related components of secondary intention healing: creation of a lattice to aid
      partial closure and compression dressings. The technique, which is widely used in
      dermatological surgery to manage cutaneous defects after operations for skin
      cancer, avoids the morbidity associated with the use of split skin grafts and
      enables early postoperative mobilisation. 

PMID- 24894711
TI  - Maxillary sinus bone lid with pedicled bone flap for foreign body removal: the
      piezoelectric device.

PMID- 24894713
TI  - Spontaneous mesenteric hematoma complicating an exacerbation of Crohn's disease:
      report of a case.
AB  - CASE PRESENTATION: Spontaneous mesenteric haematoma is a rare condition that
      occurs due to localized bleeding in the mesenteric vascular tree of a bowel
      segment in the absence of an identifiable cause. Here we report a case of
      spontaneous mesenteric haematoma during an inflammatory exacerbation of Crohn's
      disease. The patient underwent surgical management for small bowel obstruction
      secondary to Crohn's disease, however the concurrent presence of a spontaneous
      mesenteric haematoma in the mid-jejunal mesentery was successfully managed
      conservatively. CONCLUSION: This case identifies the first association of
      spontaneous mesenteric haematoma with an exacerbation of Crohn's disease and
      highlights the need to consider rare differential diagnoses such as SMH when
      performing radiological assessment of unexplained symptoms in inflammatory bowel
      disease patients.

PMID- 24894712
TI  - Comment. Re: Tetracycline: a cure all ? BJOMS 52(2014) 382-383 Kennedy et al.

PMID- 24894715
TI  - The impact of blood management on length of stay after primary total knee
      arthroplasty.
AB  - The current study investigates the impact of patient factors, surgical factors,
      and blood management on postoperative length of stay (LOS) in 516 patients who
      underwent primary total knee arthroplasty. Age, gender, type of anticoagulation,
      but not body mass index (BMI) were found to be highly significant predictors of
      an increased LOS. Allogeneic transfusion and the number of allogeneic units
      significantly increased LOS, whereas donation and/or transfusion of autologous
      blood did not. Hemoglobin levels preoperatively until 48 hours postoperatively
      were negatively correlated with LOS. After adjusting for confounding factors
      through Poisson regression, age (p = 0.001) and allogeneic blood transfusion (p =
      0.002) were the most significant determinants of LOS. Avoiding allogeneic blood
      plays an essential role in reducing the overall length of stay after primary
      total knee arthroplasty. 

PMID- 24894714
TI  - Body image in idiopathic scoliosis: a comparison study of psychometric properties
      between four patient-reported outcome instruments.
AB  - BACKGROUND: Four patient-reported outcome (PRO) instruments are commonly used to
      assess body image in idiopathic scoliosis (IS): the Quality of Life Profile for
      Spinal Deformities (QLPSD), SRS-22 Self-Image scale, Spinal Appearance
      Questionnaire (SAQ), and Trunk Appearance Perception Scale (TAPS). The aim of
      this study is to compare the psychometric properties of these instruments in
      patients with IS and report the translational/cultural adaptation of the SAQ to
      Spanish. METHODS: The four instruments in a Spanish version were administered to
      80 patients with IS aged 10 to 40 years old. The sample was stratified according
      to scoliosis magnitude (less and more than 45o). Analysis was also conducted for
      age groups. The psychometric properties studied included convergent and divergent
      construct validity, as well as internal consistency. Convergent validity was
      evaluated by correlation analysis between the self-image instruments and Cobb
      angle. Divergent validity was assessed with correlation analysis between PRO
      scores and SRS-22 dimensions scores such as Function, Pain and Mental Health.
      RESULTS: In the overall sample, each of the PRO instruments demonstrated high
      internal consistency (QLPSD Body Image, alpha = 0.80; SRS-22 Self Image, alpha =
      0.78; SAQ, alpha = 0.89; TAPS, alpha = 0.87), also both for younger and adult
      patients subgroups. Correlation with curve magnitude was significant for each of
      the four scales. However, the correlation was higher for the pictorial scales
      (SAQ Appearance r = 0.61, TAPS r = -0.62) than for the textual scales (QLPSD-bi r
      = 0.36, SRS-22 Self-Image scale r = -0.41). In the younger group, correlation
      between Cobb angle and textual scales (QLPSD-bi and SRS-22 Self-Image Scale) was
      not significant. Body Image scales showed significant correlations with SRS-22
      Pain, Function and Mental Health dimensions. CONCLUSIONS: All four instruments
      tested have good psychometric properties. Pictorial scales (SAQ Appearance and
      TAPS) correlated better with the radiological magnitude of the curve and this
      correlation is independent of age. Unexpectedly, all four scales demonstrated
      significant correlations with non-body image dimensions and the divergent
      hypothesis was not confirmed. Globally, pictorial scales showed slightly better
      construct validity to test body image perception than textual scales.

PMID- 24894716
TI  - GPER mediates activation of HIF1alpha/VEGF signaling by estrogens.
AB  - Biological responses to estrogens in normal and malignant tissues are mainly
      mediated by the estrogen receptors ERalpha and ERbeta, which function as ligand
      activated transcription factors. In addition, the G protein-coupled receptor
      GPR30 (GPER) mediates estrogenic signaling in breast cancer cells and cancer
      associated fibroblasts (CAF) that contribute to cancer progression. In this
      study, we evaluated the role elicited by GPER in the estrogen-regulated
      expression and function of vascular endothelial growth factor (VEGF) in ER
      negative breast cancer cells and CAF. We demonstrated that 17beta-estradiol (E2)
      and the GPER-selective ligand G-1 triggered a GPER/EGFR/ERK/c-fos signaling
      pathway that leads to increased VEGF via upregulation of HIF1alpha. In further
      extending the mechanisms involved in E2-supported angiogenesis, we also showed
      that conditioned medium from CAF treated with E2 and G-1 promoted human
      endothelial tube formation in a GPER-dependent manner. In vivo, ligand-activated
      GPER was sufficient to enhance tumor growth and the expression of HIF1alpha,
      VEGF, and the endothelial marker CD34 in a mouse xenograft model of breast
      cancer. Our findings offer important new insights into the ability of estrogenic
      GPER signaling to trigger HIF1alpha-dependent VEGF expression that supports
      angiogenesis and progression in breast cancer.

PMID- 24894717
TI  - Germline mutations in BAP1 impair its function in DNA double-strand break repair.
AB  - The BRCA1-associated deubiquitylase BAP1 is mutated in several cancers, most
      notably mesothelioma and melanoma, where it is thought to promote oncogenesis. In
      this study, we present evidence that BAP1 functions as part of the DNA damage
      response (DDR). We found that BAP1 mediates rapid poly(ADP-ribose)-dependent
      recruitment of the polycomb deubiquitylase complex PR-DUB to sites of DNA damage.
      Furthermore, we identified BAP1 as a phosphorylation target for the DDR kinase
      ATM. Functionally, BAP1 promoted repair of DNA double-strand breaks, enhancing
      cell survival after DNA damage. Our results highlight the importance of ubiquitin
      turnover at sites of DNA damage, and they provide a mechanism to account for the
      tumor-suppressive function of BAP1.

PMID- 24894718
TI  - Functional antagonism between nociceptin/orphanin FQ and corticotropin-releasing
      factor in rat anxiety-related behaviors: involvement of the serotonergic system.
AB  - Nociceptin/orphanin FQ (N/OFQ) acts as an anxiolytic-like agent in the rat and
      behaves as a functional antagonist of corticotropin-releasing factor (CRF) due to
      its ability to oppose CRF biological actions. In response to stress, CRF triggers
      changes in neurotransmitter systems including serotonin (5-HT). The role of 5
      HT1A receptor in anxiety has been supported by preclinical and clinical studies.
      The present study investigated the possible functional antagonism between N/OFQ
      (1nmol/rat) and CRF (0.2nmol/rat) in anxiety-related conditions in rats, using
      elevated plus maze and defensive burying tests, in order to confirm previous
      literature results. Moreover, possible changes in the serotonergic system were
      studied in areas rich of serotonergic neurons: frontal cortex and pons. In both
      tests N/OFQ showed anxiolytic-like effects while CRF displayed anxiogenic-like
      effects. N/OFQ before CRF treatment counteracted the anxiogenic-like effects
      evoked by CRF. In frontal cortex, N/OFQ significantly decreased 5-HT levels but
      did not modify the hydroxyindoleacetic acid (5-HIAA) ones; CRF modified neither 5
      HT nor 5-HIAA content but counteracted changes induced by N/OFQ alone. In pons,
      N/OFQ induced no change in serotonergic activity while CRF significantly
      decreased 5-HT levels and increased 5-HIAA content. The two peptides' combination
      reinstated serotonergic parameters to controls. In frontal cortex, N/OFQ
      increased the 5HT1A receptor density but reduced its affinity, while CRF alone
      did not induce any change. In pons, CRF decreased 5HT1ABmax and KD whereas N/OFQ
      was ineffective. All biochemical modifications were reverted by N/OFQ plus CRF
      treatment. The present study confirms that N/OFQ counteracts CRF anxiogenic-like
      effects in the behavioral tests evaluated. These effects may involve central
      serotonergic mechanisms since N/OFQ plus CRF induces a reversion of serotonergic
      changes provoked by single peptide. Our data support the hypothesis that N/OFQ
      may behave as functional CRF antagonist, this action being of interest for the
      treatment of anxiety disorders.

PMID- 24894719
TI  - In vivo study of transepithelial potential difference (TEPD) in proximal
      convoluted tubules of rat kidney by synchronization modulation electric field.
AB  - Synchronization modulation (SM) electric field has been shown to effectively
      activate function of Na(+)/K(+) pumps in various cells and tissues, including
      skeletal muscle cells, cardiomyocyte, monolayer of cultured cell line, and
      peripheral blood vessels. We are now reporting the in vivo studies in application
      of the SM electric field to kidney of living rats. The field-induced changes in
      the transepithelial potential difference (TEPD) or the lumen potential from the
      proximal convoluted tubules were monitored. The results showed that a short time
      (20 s) application of the SM electric field can significantly increase the
      magnitude of TEPD from 1-2 mV to about 20 mV. The TEPD is an active potential
      representing the transport current of the Na/K pumps in epithelial wall of renal
      tubules. This study showed that SM electric field can increase TEPD by activation
      of the pump molecules. Considering renal tubules, many active transporters are
      driven by the Na(+) concentration gradient built by the Na(+)/K(+) pumps,
      activation of the pump functions and increase in the magnitude of TEPD imply that
      the SM electric field may improve reabsorption functions of the renal tubules. 

PMID- 24894720
TI  - Application of amphipols for structure-functional analysis of TRP channels.
AB  - Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for
      stabilizing integral membrane proteins in detergent-free conditions for
      structural and functional studies. Transient receptor potential (TRP) ion
      channels function as tetrameric protein complexes in a diverse range of cellular
      processes including sensory transduction. Mammalian TRP channels share ~20 %
      sequence similarity and are categorized into six subfamilies: TRPC (canonical),
      TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML
      (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane
      proteins, structural studies of TRP channels have been limited. Recently, A8-35
      was essential in resolving the molecular architecture of the nociceptor TRPA1 and
      led to the determination of a high-resolution structure of the thermosensitive
      TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG)
      detergents have also proven to be useful in stabilizing TRP channels for
      structural analysis. In this review, we will discuss the impacts of amphipols and
      MNG detergents on structural studies of TRP channels by cryo-EM. We will compare
      how A8-35 and MNG detergents interact with the hydrophobic transmembrane domains
      of TRP channels. In addition, we will discuss what these cryo-EM studies reveal
      on the importance of screening different types of surfactants toward determining
      high-resolution structures of TRP channels. 

PMID- 24894723
TI  - Electrically and optically readable light emitting memories.
AB  - Electrochemical metallization memories based on redox-induced resistance
      switching have been considered as the next-generation electronic storage devices.
      However, the electronic signals suffer from the interconnect delay and the
      limited reading speed, which are the major obstacles for memory performance. To
      solve this problem, here we demonstrate the first attempt of light-emitting
      memory (LEM) that uses SiO2 as the resistive switching material in tandem with
      graphene-insulator-semiconductor (GIS) light-emitting diode (LED). By utilizing
      the excellent properties of graphene, such as high conductivity, high robustness
      and high transparency, our proposed LEM enables data communication via electronic
      and optical signals simultaneously. Both the bistable light-emission state and
      the resistance switching properties can be attributed to the conducting filament
      mechanism. Moreover, on the analysis of current-voltage characteristics, we
      further confirm that the electroluminescence signal originates from the carrier
      tunneling, which is quite different from the standard p-n junction model. We
      stress here that the newly developed LEM device possesses a simple structure with
      mature fabrication processes, which integrates advantages of all composed
      materials and can be extended to many other material systems. It should be able
      to attract academic interest as well as stimulate industrial application. 

PMID- 24894721
TI  - Apple cider vinegar modulates serum lipid profile, erythrocyte, kidney, and liver
      membrane oxidative stress in ovariectomized mice fed high cholesterol.
AB  - The purpose of this study was to investigate the potentially beneficial effects
      of apple cider vinegar (ACV) supplementation on serum triglycerides, total
      cholesterol, liver and kidney membrane lipid peroxidation, and antioxidant levels
      in ovariectomized (OVX) mice fed high cholesterol. Four groups of ten female mice
      were treated as follows: Group I received no treatment and was used as control.
      Group II was OVX mice. Group III received ACV intragastrically (0.6% of feed),
      and group IV was OVX and was treated with ACV as described for group III. The
      treatment was continued for 28 days, during which the mice were fed a high
      cholesterol diet. The lipid peroxidation levels in erythrocyte, liver and kidney,
      triglycerides, total, and VLDL cholesterol levels in serum were higher in the OVX
      group than in groups III and IV. The levels of vitamin E in liver, the kidney and
      erythrocyte glutathione peroxidase (GSH-Px), and erythrocyte-reduced glutathione
      (GSH) were decreased in group II. The GSH-Px, vitamin C, E, and beta-carotene,
      and the erythrocyte GSH and GSH-Px values were higher in kidney of groups III and
      IV, but in liver the vitamin E and beta-carotene concentrations were decreased.
      In conclusion, ACV induced a protective effect against erythrocyte, kidney, and
      liver oxidative injury, and lowered the serum lipid levels in mice fed high
      cholesterol, suggesting that it possesses oxidative stress scavenging effects,
      inhibits lipid peroxidation, and increases the levels of antioxidant enzymes and
      vitamin.

PMID- 24894722
TI  - A theoretical model of glucose transport suggests symmetric GLUT1 characteristics
      at placental membranes.
AB  - The process of glucose transport via the placenta is not fully deciphered. Here,
      we apply a theoretical model to compute glucose fluxes via the terminal villi of
      the human placenta for various sets of parameter values and conclude on
      characteristics of transport across the two bordering membranes. Based on
      available measured data, the spatial geometry of the terminal villi is being
      simulated. Within this region, glucose concentrations and fluxes are computed by
      a numerical scheme that solves the diffusion equation with boundary conditions
      that account for transporter mediated diffusion at the membranes. Feasible
      parameter values (ones that induce physiological glucose fluxes) are determined
      for four optional symmetry characteristics of the membranes. Confronting computed
      results with clinical knowledge reveals the most plausible scenario-symmetric
      activity of the transporter at the microvillous membrane. Thus, sensitivity
      analysis of the computed results enables deduction about micro-scale mechanisms
      at the bordering membranes based on macro-scale knowledge. 

PMID- 24894725
TI  - Analysis of higher-order aberrations in eyes having undergone intraocular lens
      suturing.

PMID- 24894724
TI  - Intrinsic multipotential mesenchymal stromal cell activity in gelatinous
      Heberden's nodes in osteoarthritis at clinical presentation.
AB  - INTRODUCTION: Gelatinous Heberden's nodes (HNs), also termed synovial cysts, are
      a common form of generalized osteoarthritis (OA). We sought to determine whether
      HN cases at clinical presentation contained multipotential stromal cells (MSCs)
      and to explore whether such cells were more closely related to bone marrow (BM)
      or synovial fluid (SF) MSCs by transcriptional analysis. METHODS: At clinical
      presentation, gelatinous material was extracted/extruded from the distal
      phalangeal joint of OA patients with HNs. From this, plastic adherent cells were
      culture-expanded for phenotypic and functional characterization and comparison
      with BM- and SF-MSCs. Mesenchymal related gene expression was studied by using a
      custom-designed TaqMan Low Density Array to determine transcriptional
      similarities between different MSC groups and skin fibroblasts. RESULTS: In all
      cases, HN material produced MSC-like colonies. Adherent cultures displayed an MSC
      phenotype (CD29(+), CD44(+), CD73(+), CD81(+), and CD90(+) and CD14(-) CD19(-),
      CD31(-), CD34(-), CD45(-), and HLADR(-)) and exhibited osteogenic, chondrogenic
      lineage differentiation but weak adipogenesis. Gene cluster analysis showed that
      HN-MSCs were more closely related to SF- than normal or OA BM-MSCs with
      significantly higher expression of synovium-related gene markers such as bone
      morphogenic protein 4 (BMP4), bone morphogenetic protein receptor type 1A
      (BMPR1A), protein/leucine-rich end leucine-rich repeat protein (PRELP), secreted
      frizzled-related protein 4 (SFRP4), and tumor necrosis factor alpha-induced
      protein 6 (TNFAIP6) (P <0.05). CONCLUSIONS: Gelatinous HNs derived from hand OA
      at clinical presentation contain a population of MSCs that share transcriptional
      similarities with SF-derived MSCs. Their aberrant entrapment within the synovial
      cysts may impact on their normal role in joint homeostasis.

PMID- 24894726
TI  - Assessment of the impact of the London Olympics 2012 on selected non
      genitourinary medicine clinic sexual health services.
AB  - With minimal information on sexual health provision during mass-gathering events,
      our aim was to describe the use of sexual health, contraceptive, sex worker and
      sexual assault services during the London 2012 Olympics. We analysed data from
      five sources. One contraceptive service provider reported a 10% increase in
      attendance during the main Games, while emergency contraception prescriptions
      rose during the main Olympics, compared to the week before, but were similar or
      lower than at the beginning and end of the summer period. A health telephone
      advice line reported a 16% fall in sexual health-related calls during the main
      Olympics, but a 33% increase subsequently. London sexual assault referral centres
      reported that 1.8% of sexual assaults were Olympics-linked. A service for sex
      workers reported that 16% started working in the sex industry and 7% moved to
      London to work during the Olympics. Fifty-eight per cent and 45% of sex workers
      reported fewer clients and an increase in police crack-downs, respectively. Our
      results show a change in activity across these services during the 2012 summer,
      which may be associated with the Olympics. Our data are a guide to other services
      when anticipating changes in service activity and planning staffing for mass
      gathering events. 

PMID- 24894727
TI  - Variation in child body mass index patterns by race/ethnicity and maternal
      nativity status in the United States and England.
AB  - This paper examines body mass index (BMI) trajectories among children from
      different race/ethnic and maternal nativity backgrounds in the United States and
      England from early- to middle-childhood. This study is the first to examine
      race/ethnic and maternal nativity differences in BMI trajectories in both
      countries. We use two longitudinal birth cohort studies-The Fragile Families and
      Child Wellbeing Study (n = 3,285) for the United States and the Millennium Cohort
      Study (n = 6,700) for England to estimate trajectories in child BMI by
      race/ethnicity and maternal nativity status using multilevel growth models. In
      the United States our sample includes white, black, and Hispanic children; in
      England the sample includes white, black, and Asian children. We find significant
      race/ethnic differences in the initial BMI and BMI trajectories of children in
      both countries, with all non-white groups having significantly steeper BMI growth
      trajectories than whites. Nativity differences in BMI trajectories vary by
      race/ethnic group and are only statistically significantly higher for children of
      foreign-born blacks in England. Disparities in BMI trajectories are pervasive in
      the United States and England, despite lower overall BMI among English children.
      Future studies should consider both race/ethnicity and maternal nativity status
      subgroups when examining disparities in BMI in the United States and England.
      Differences in BMI are apparent in early childhood, which suggests that
      interventions targeting pre-school age children may be most effective at stemming
      childhood disparities in BMI.

PMID- 24894728
TI  - Effect of previous miscarriage on depressive symptoms during subsequent pregnancy
      and postpartum in the first baby study.
AB  - Our objective was to test the hypothesis that nulliparous women with a history of
      miscarriage have an increased risk of depression during late pregnancy, and at 1,
      6, and 12 months postpartum compared to women without a history of miscarriage.
      We conducted secondary analysis of a longitudinal cohort study, the First Baby
      Study, and compared 448 pregnant women with a history of miscarriage to 2,343
      pregnant women without a history of miscarriage on risk of probable depression
      (score >12 on the Edinburgh Postnatal Depression Scale). Logistic regression
      models were used to estimate odds ratios at each time point and generalized
      estimating equations were used to obtain estimates in longitudinal analysis.
      Women with a history of miscarriage were not more likely than woman without a
      history of miscarriage to score in the probable depression range during the third
      trimester or at 6 or 12 months postpartum but were more likely at 1 month
      postpartum, after adjustment for sociodemographic factors (OR 1.66, 95% CI 1.03
      2.69). Women with a history of miscarriage may be more vulnerable to depression
      during the first month postpartum than women without prior miscarriage, but this
      effect does not appear to persist beyond this time period. We support the
      promotion of awareness surrounding this issue and recommend that research is
      planned to identify risk factors that may position a woman with a history of
      miscarriage to be at higher risk for depression.

PMID- 24894729
TI  - Do black-white racial disparities in breastfeeding persist in the military
      community?
AB  - We conduct a comparative analysis of breastfeeding behavior between military and
      civilian-affiliated mothers. Our focus is on African American mothers among whom
      breastfeeding rates are lowest. The military context may mitigate conditions
      associated with low breastfeeding prevalence by (a) providing stable employment
      and educational opportunities to populations who face an otherwise poor labor
      market and (b) providing universal healthcare that includes breastfeeding
      consultation. Using pregnancy risk assessment monitoring system (PRAMS) data for
      which we received special permission from each state to flag military
      affiliation, we analyze civilians and military affiliate in breastfeeding
      initiation using logistic regression and breastfeeding duration using Cox
      proportional hazard analysis. We find that breastfeeding is more prevalent among
      all women in the military setting and that the black-white gap in breastfeeding
      duration common among civilians is significantly reduced among military
      affiliates. Breastfeeding is a crucial component of maternal and child health and
      eliminating racial disparities in its prevalence is a public health priority.
      This study is the first to identify the military as an important institutional
      context that deserves closer examination to glean potential policy implications
      for civilian society. 

PMID- 24894730
TI  - Timing of breastfeeding initiation and exclusivity of breastfeeding during the
      first month of life: effects on neonatal mortality and morbidity--a systematic
      review and meta-analysis.
AB  - The purpose of this study was to review the evidence on the effect of initiation
      of breastfeeding early after birth and of exclusive breastfeeding during the
      first month in reducing neonatal mortality and morbidity. We searched Cochrane
      and PubMed databases for all available papers addressing our review questions and
      identified eleven papers. Data were extracted using a standard abstraction form.
      Evidence was assessed using the Grading of Recommendations Assessment,
      Development and Evaluation system. Meta-analysis was done using STATA 11.0. Early
      initiation of breastfeeding was associated with a reduced risk of neonatal
      mortality. Initiating breastfeeding after the first hour doubled the risk of
      neonatal mortality. Exclusively breastfed neonates had a lower risk of mortality
      and infection-related deaths in the first month than partially breastfed
      neonates. Exclusively breastfed neonates also had a significantly lower risk of
      sepsis, diarrhea and respiratory infections compared with those partially
      breastfed. The pooled evidence indicates that substantial benefits in reducing
      neonatal mortality and morbidity can be achieved with effective promotion of
      early initiation of breastfeeding and exclusive breastfeeding during the first
      month of life. 

PMID- 24894731
TI  - Dental pain and associated factors among pregnant women: an observational study.
AB  - The present study aimed to determine the prevalence of dental pain during
      pregnancy and its association with sociodemographic factors and oral health
      conditions among 315 pregnant women in South Brazil. Participants were
      interviewed to obtain sociodemographic data, such as age, educational level,
      employment status, family income, and marital and parity status. Medical and
      dental histories were also collected, including the occurrence of dental pain and
      the use of dental services during pregnancy. Clinical examinations were performed
      to assess the presence of visible plaque and gingival bleeding and to calculate
      the decayed, missing, and filled teeth index. Means and standard deviations of
      continuous variables and frequencies and percentages of categorical variables
      were calculated. Independent variables were included in a multivariate logistic
      regression analysis. A total of 173 (54.9 %) pregnant women reported dental pain
      during pregnancy. After adjustment of the analysis, caries activity remained the
      main determinant of dental pain (odds ratio 3.33, 95 % CI 1.67-6.65). The
      prevalence of dental pain during pregnancy was high and the presence of caries
      activity was a determinant of dental pain. Moreover, access to oral health care
      was low, despite pregnant women's increased need for dental assistance.

PMID- 24894732
TI  - Intrapartum epidural analgesia and onset of lactation: a prospective study in an
      Italian birth centre.
AB  - The objective of this study is to investigate the relationship between epidural
      analgesia (EDA) in labor and the onset of lactation in healthy women after birth.
      In a Regional Perinatal Center in northern Italy, women who had had a vaginal
      delivery were recruited by convenience sampling. Analyses were carried out on the
      data of 366 women. 209 women received EDA and 157 women did not receive EDA or
      any other pharmacological analgesia. A structured follow-up was carried out
      interviewing women by telephone after 5 days and, a second time, 20 days after
      delivery. The primary outcome was the time (in hours) of the onset of lactation.
      Timing of the onset of lactation in the EDA and non-EDA groups did not
      statistically differ (p = 0.15), although the non-EDA group was more likely to
      initiate breastfeeding. On the basis of the results of this study, we concluded
      that intrapartum EDA does not have an effect on delays in the onset of lactation.

PMID- 24894733
TI  - Validity and reliability of the Brazilian version of Yale-Brown obsessive
      compulsive scale-shopping version (YBOCS-SV).
AB  - INTRODUCTION: The Yale-Brown Obsessive Compulsive Scale-Shopping Version (YBOCS
      SV) is considered the gold standard in the assessment of shopping severity. It is
      designed to assess cognitions and behaviors relating to compulsive buying
      behavior. The present study aims to assess the validity of the Brazilian version
      of this scale. METHODS: For the study, composed the sample 610 participants: 588
      subjects of a general population and 22 compulsive buyers. Factorial analysis was
      performed to assess the relations and the correlation between the YBOCS-SV, the
      Compulsive Buying Scale (CBS), and Richmond Compulsive Buying Scale (RCBS), was
      assessed using Pearson coefficient, for study of convergent and divergent
      validity. Cronbach's alpha coefficients were used to assess internal consistency.
      RESULTS: The results show good to excellent psychometric parameters for the YBOCS
      SV in its Brazilian version. With regard to correlations, the YBOCS-SV is
      inversely and proportionally correlated with CBS and the RCBS, indicating that
      the YBOCS-SV is an excellent instrument for screening compulsive buying. The
      YBOCS-SV presented high alpha coefficient of Cronbach's alpha (0.92),
      demonstrating good reliability. CONCLUSIONS: The Brazilian version of the YBOCS
      SV is indicated to diagnose compulsive buying disorder, and likely use for the
      purposes intended in the Brazilian population.

PMID- 24894735
TI  - Does mindfulness have potential in eating disorders prevention? A preliminary
      controlled trial with young adult women.
AB  - AIM: This preliminary randomized controlled trial assessed the feasibility of a
      pilot mindfulness-based intervention with respect to reducing the risk of eating
      disorders in young women. METHODS: Forty-four young adult women with body image
      concerns (Mage  = 20.57, SD = 3.22) were randomly allocated to a mindfulness
      based or a dissonance-based intervention (3 * 1 h weekly sessions), or to
      assessment-only control. Self-report measures of eating disorder risk factors,
      symptoms and related psychosocial impairment were compared at baseline, post
      intervention, and at 1- and 6-month follow up. RESULTS: At post-intervention,
      acceptability ratings for both interventions were high. Mindfulness participants
      demonstrated statistically significant improvements relative to control at post
      intervention for weight and shape concern, dietary restraint, thin ideal
      internalization, eating disorder symptoms and related psychosocial impairment;
      however, these gains were largely lost over follow up. Dissonance participants
      did not show statistically significant improvements relative to control on any
      outcomes, despite small to moderate effect sizes. CONCLUSIONS: These preliminary
      findings demonstrate the acceptability and short-term efficacy of a mindfulness
      based approach to reducing the risk of disordered eating in young women. This
      provides support for the continued evaluation of mindfulness in the prevention
      and early intervention of eating disorders, with increased efforts to produce
      maintenance of intervention gains.

PMID- 24894734
TI  - Parathyroid adenoma detected with 99mTc-tetrofosmin dual-phase scintigraphy: a
      case report.
AB  - BACKGROUND: Tc-sestamibi is the most frequently used radionuclide agent for the
      detection of parathyroid adenomas in the clinical setting. However, Tc
      tetrofosmin is another such agent that may be used for this purpose. This case
      report presents the significance and practicality of 99mTc-tetrofosmin for the
      diagnosis of parathyroid adenomas with probable high p-glycoprotein levels. CASE
      PRESENTATION: A 45-year-old woman was referred to our Nuclear Department with a
      palpable neck nodule suspicious for parathyroid adenoma. She had no significant
      medical history or other accompanying symptoms. Blood examination results were
      normal with the exception of the parathormone level which was high at 167.2
      pg/ml. Neck ultrasonography revealed a hypoechoic mass near the lower pole of the
      thyroid gland. 99m Tc-tetrofosmin dual-phase scintigraphy with early and delayed
      images was performed and the results supported the presupposition of parathyroid
      adenoma as shown by increased radiopharmaceutical levels near the lower left
      thyroid gland on the early image that disappeared on the delayed image. Moreover,
      TcO4- thyroid scintigraphy results excluded thyroid pathology. Two months after
      the diagnosis, parathyroidectomy was successfully performed without postoperative
      complications. The pathology report and clinical response to a gradual decrease
      of parathormone confirmed the initial diagnosis. CONCLUSION: We strongly
      recommend the use of reverse 99m Tc-tetrofosmin scintigraphy as a useful and safe
      examination technique for the diagnosis of parathyroid adenomas.

PMID- 24894736
TI  - Non-specific psychological distress in women undergoing noninvasive prenatal
      testing because of advanced maternal age.
AB  - OBJECTIVE: The objective of our study was to describe our clinical experience in
      providing noninvasive prenatal testing (NIPT) for fetal aneuploidy to pregnant
      women, highlighting the degree of non-specific psychological distress. METHODS:
      Data were collected from Japanese women who were offered and underwent NIPT after
      genetic counseling and control pregnant women who did not undergo NIPT as part of
      the Japan Environment and Children's Study Control A planning. The degree of
      mental distress was assessed using the Kessler 6 (K6) screening scale with a
      score of >=10 indicating depression or anxiety disorder. RESULTS: Among the 505
      women who underwent NIPT because of advanced maternal age, 9.1% had a K6 score of
      >=10. Compared with matched controls (n = 1010) adjusted for maternal age and
      gestational age, the NIPT group showed a trend toward higher K6 scores (odds
      ratio 1.44, 95% confidence interval 0.97-2.13, P = 0.07). Higher K6 scores were
      associated with women whose husbands were the primary decision makers during NIPT
      counseling (P = 0.06). CONCLUSIONS: Women electing NIPT tend to have higher
      scores of depression/anxiety, and those with higher depression scores tended to
      defer the decision to their husbands.

PMID- 24894737
TI  - Monitoring of occupational and environmental aeroallergens-- EAACI Position
      Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology &
      Air Pollution.
AB  - Exposure to high molecular weight sensitizers of biological origin is an
      important risk factor for the development of asthma and rhinitis. Most of the
      causal allergens have been defined based on their reactivity with IgE antibodies,
      and in many cases, the molecular structure and function of the allergens have
      been established. Significant information on allergen levels that cause
      sensitization and allergic symptoms for several major environmental and
      occupational allergens has been reported. Monitoring of high molecular weight
      allergens and allergen carrier particles is an important part of the management
      of allergic respiratory diseases and requires standardized allergen assessment
      methods for occupational and environmental (indoor and outdoor) allergen
      exposure. The aim of this EAACI task force was to review the essential points for
      monitoring environmental and occupational allergen exposure including sampling
      strategies and methods, processing of dust samples, allergen analysis, and
      quantification. The paper includes a summary of different methods for sampling
      and allergen quantification, as well as their pros and cons for various exposure
      settings. Recommendations are being made for different exposure scenarios. 

PMID- 24894738
TI  - Genetic diversity and population structure among pea (Pisum sativum L.) cultivars
      as revealed by simple sequence repeat and novel genic markers.
AB  - Field pea (Pisum sativum L.) is an important cool season legume crop widely grown
      around the world. This research provides a basis for selection of pea germplasm
      across geographical regions in current and future breeding and genetic mapping
      efforts for pea improvement. Eleven novel genic markers were developed from pea
      expressed sequence tag (EST) sequences having significant similarity with gene
      calls from Medicago truncatula spanning at least one intron. In this study, 96
      cultivars widely grown or used in breeding programs in the USA and Canada were
      analyzed for genetic diversity using 31 microsatellite or simple sequence repeat
      (SSR) and 11 novel EST-derived genic markers. The polymorphic information content
      varied from 0.01-0.56 among SSR markers and 0.04-0.43 among genic markers. The
      results showed that SSR and EST-derived genic markers displayed one or more
      highly reproducible, multi-allelic, and easy to score loci ranging from 200 to
      700 bp in size. Genetic diversity was assessed through unweighted neighbor
      joining method, and 96 varieties were grouped into three main clusters based on
      the dissimilarity matrix. Four subpopulations were determined through STRUCTURE
      analysis with no significant geographic separation of the subpopulations. The
      findings of the present study can be used to select diverse genotypes to be used
      as parents of crosses aimed for breeding improved pea cultivars. 

PMID- 24894739
TI  - Analysis of the genetics of boar taint reveals both single SNPs and regional
      effects.
AB  - BACKGROUND: Boar taint is an offensive urine or faecal-like odour, affecting the
      smell and taste of cooked pork from some mature non-castrated male pigs.
      Androstenone and skatole in fat are the molecules responsible. In most pig
      production systems, males, which are not required for breeding, are castrated
      shortly after birth to reduce the risk of boar taint. There is evidence for
      genetic variation in the predisposition to boar taint.A genome-wide association
      study (GWAS) was performed to identify loci with effects on boar taint. Five
      hundred Danish Landrace boars with high levels of skatole in fat (>0.3 MUg/g),
      were each matched with a litter mate with low levels of skatole and measured for
      androstenone. DNA from these 1,000 non-castrated boars was genotyped using the
      Illumina PorcineSNP60 Beadchip. After quality control, tests for SNPs associated
      with boar taint were performed on 938 phenotyped individuals and 44,648 SNPs.
      Empirical significance thresholds were set by permutation (100,000). For
      androstenone, a 'regional heritability approach' combining information from
      multiple SNPs was used to estimate the genetic variation attributable to
      individual autosomes. RESULTS: A highly significant association was found between
      variation in skatole levels and SNPs within the CYP2E1 gene on chromosome 14
      (SSC14), which encodes an enzyme involved in degradation of skatole. Nominal
      significance was found for effects on skatole associated with 4 other SNPs
      including a region of SSC6 reported previously. Genome-wide significance was
      found for an association between SNPs on SSC5 and androstenone levels and nominal
      significance for associations with SNPs on SSC13 and SSC17. The regional analyses
      confirmed large effects on SSC5 for androstenone and suggest that SSC5 explains
      23% of the genetic variation in androstenone. The autosomal heritability analyses
      also suggest that there is a large effect associated with androstenone on SSC2,
      not detected using GWAS. CONCLUSIONS: Significant SNP associations were found for
      skatole on SSC14 and for androstenone on SSC5 in Landrace pigs. The study agrees
      with evidence that the CYP2E1 gene has effects on skatole breakdown in the liver.
      Autosomal heritability estimates can uncover clusters of smaller genetic effects
      that individually do not exceed the threshold for GWAS significance.

PMID- 24894740
TI  - Estimating the magnitude of colorectal cancers prevented during the era of
      screening: 1976 to 2009.
AB  - BACKGROUND: Ideally, screening detects cancer at a more curable stage and, as a
      result, decreases the rate of subsequent diagnosis at a late stage. Although it
      is suggested that some cancer screening tests have led to substantial increases
      in early-stage incidence with only marginal reductions in late-stage incidence
      (eg mammography), the association between temporal trends in colorectal cancer
      screening and its cumulative impact on colorectal cancer incidence is unknown.
      METHODS: Colorectal cancer incidence data spanning over 3 decades (1976-2009)
      were collected from the Surveillance, Epidemiology, and End Results database.
      Data on screening use spanning the period from 1986 to 2010 were collected from
      the National Cancer Institute Cancer Trends Progress Report, and trends in the
      incidence of early-stage (in situ, local) and late-stage (regional, distant)
      colorectal cancer were examined among adults aged >=50 years. RESULTS: From 1987
      to 2010--the years for which screening data were available--the percentage of
      adults aged >=50 years who underwent screening rose from 34.8% to 66.1% (which
      included increases in colonoscopy). During that time, the incidence of late-stage
      colorectal cancer decreased from 118 to 74 cases per 100,000 population (P <
      .001). The incidence of early-stage colorectal cancer also decreased, from 77 to
      67 cases per 100,000 population (P < .001). After adjusting for underlying trends
      in cancer incidence, colorectal screening was associated with a reduction of
      approximately 550,000 cases of colorectal cancer over the past 3 decades in the
      United States. CONCLUSIONS: There has been a significant decline in the incidence
      of colorectal cancer in the United States, particularly for late-stage disease,
      during a time of increasing rates of screening.

PMID- 24894741
TI  - Asthma and smoking--healthcare needs and preferences of adults with asthma who
      smoke.
AB  - OBJECTIVE: People with asthma smoke at least as much as, if not more than, people
      without asthma. The aim of this study was to explore the unique healthcare needs
      and preferences of smokers with asthma, in terms of smoking topography and
      initiation, perceived interplay between asthma and smoking, motivation and
      readiness to quit, and proposed smoking cessation techniques. METHODS:
      Qualitative, semi-structured, in-depth telephone interviews with adult smokers
      who have concurrent asthma were conducted. Participants were recruited through
      flyers displayed at community pharmacies, general practice surgeries, university
      campuses, and respiratory clinics of tertiary hospitals and through an
      advertisement on the "Asthma Foundation" website. Recorded interviews were
      transcribed verbatim and analysed using NVivo 10 software (QSR International,
      Melbourne, Victoria, Australia). Obtained data were content-analysed for emergent
      themes using the 'framework approach'. RESULTS: Twenty-four semi-structured
      interviews were conducted. Most participants believed that smoking often worsens
      their asthma and increases the frequency and severity of their symptoms. Fear of
      asthma-related exacerbations and poor self-control appeared to be the major
      triggers for quitting smoking. Most patients reported being motivated to quit
      smoking; however, in many cases, determination and strong will power need to be
      coupled with public, social, professional, and therapeutic support to achieve and
      maintain success. CONCLUSIONS: Given the unique needs of people with asthma who
      smoke, it is imperative that evidence-based smoking cessation programs be
      designed and tailored to assist them in effectively quitting smoking.

PMID- 24894742
TI  - Reliability in reporting asthma history and age at asthma onset.
AB  - BACKGROUND: Evaluation of the prevalence and incidence of asthma and research
      into its etiology often rely on self-reported information. We conducted this
      analysis to investigate reliability in reporting asthma history across categories
      of demographic and socio-economic characteristics. METHODS: We analyzed data from
      3109 participants in the Coronary Artery Risk Development in Young Adults study,
      a longitudinal study of African-American and white adults. Responses to self
      administered questionnaires completed at 15- and 20-year follow-up exams were
      used to evaluate agreement in reporting asthma history and age at diagnosis and
      assess variation in agreement across categories of demographic and health-related
      characteristics. RESULTS: A history of asthma was reported by 12% of participants
      at the 15-year exam and 11% of participants at the 20-year exam, with 97%
      agreement and an overall Kappa coefficient of 0.845 (95% confidence interval:
      0.815-0.874). Kappa coefficients were higher among women than men and increased
      monotonically across categories of educational attainment. One-hundred eight
      participants (35%) reported exactly the same age at diagnosis at the two time
      points; for another 120 (39%), the difference in reported ages was <=2 years. Age
      at asthma diagnosis reported at the 20-year exam was, on an average, 1 year (SD:
      5.2) older than that reported at the 15-year exam. CONCLUSIONS: Five-year
      reliability in self-reported asthma history is high, and variation in reporting
      age at diagnosis is low across categories of participant characteristics.
      Nevertheless, agreement in responses at two times does not guarantee that self
      administered questionnaires are sensitive tools for detecting a true asthma
      history.

PMID- 24894743
TI  - Burden of asthma among children in a developing megacity: childhood asthma study,
      Pakistan.
AB  - OBJECTIVES: Global burden of childhood asthma has increased in the past few
      decades, particularly in low-income countries. In Pakistan, there is a lack of
      community-based epidemiological studies estimating the burden of asthma among
      children. This study determined the prevalence and predictors of asthma among
      children 3-17 years of age in Karachi, Pakistan. METHODS: A two-stage community
      based representative cross-sectional survey was conducted in Karachi from March
      2012 to April 2013 comprising 1046 children aged 3-17 years. Of 7500 clusters, 80
      were randomly selected, and of these, 15 children per cluster were enrolled
      randomly. A translated and pre-tested version of International Study of Asthma
      and Allergies in Children questionnaire was administered. RESULTS: The overall
      prevalence of asthma among study participants was 10.2% (95% CI: 8.4-12.0).
      Asthma was more likely to occur among boys (adj. OR: 2.5, 95% CI: 1.6-4.0),
      children in the younger age group (3-7 years) (adj. OR: 2.9, 95% CI: 1.7-4.8),
      those living in households with ill-ventilated kitchens (adj. OR: 1.8, 95% CI:
      1.1-3.1), having family history of asthma (adj. OR: 2.3, 95% CI: 1.3-3.9) and
      those of the Sindhi ethnicity (adj. OR: 2.2, 95% CI: 1.1-4.4). CONCLUSION: This
      study is the first robust evidence regarding asthma among children in Pakistan,
      reporting a high burden in this group. Family history, male gender, Sindhi
      ethnicity and ill-ventilated kitchen were identified as important predictors of
      asthma. Targeted preventive measures and intervention studies are required to
      better understand and reduce the burden of asthma among children in Pakistan.

PMID- 24894744
TI  - Cerebral anatomical changes in female asthma patients with and without depression
      compared to healthy controls and patients with depression.
AB  - BACKGROUND: Population-based studies have demonstrated that asthma patients with
      depression symptoms are more likely to have poor asthma control and worse asthma
      outcomes. However, the underlying mechanism of the relationship between asthma
      and depression is still unclear. The present study aimed to examine the cerebral
      anatomical changes in female asthma patients with and without depression.
      METHODS: Using structural magnetic resonance imaging (MRI) and a voxel-based
      morphometry technique, the primary effects of and the interaction between asthma
      and depression were analyzed. The cerebral gray matter volume (GMV) was compared
      between the groups. Correlation analyses between the GMV value of the brain
      regions and the clinical parameters were completed. RESULTS: The interaction
      effect of asthma and depression was found on the right superior temporal gyrus
      (STG) and the left middle temporal gyrus. Patients with both asthma and
      depression showed less GMV in the right STG, the bilateral precuneus, and the
      right superior frontal gyrus compared to patients with asthma only. The GMV of
      the right STG showed a decrement form among the asthma only group, healthy
      controls and asthma plus depression group. In patients with asthma and
      depression, the volume of the right STG was positively correlated with PD20 (r =
      0.714, p = 0.047) and negatively correlated with the nocturnal awakening score in
      the Asthma Control Test (r = -0.061, p = 0.038). CONCLUSION: Current findings
      provided convergent evidence to support the critical role of the right STG in the
      brain mechanism that mediates asthma and depression.

PMID- 24894746
TI  - Hepatocellular carcinoma: a comprehensive overview of surgical therapy.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide,
      with a rising incidence in the United States. The increase in medical and locally
      ablative therapies have improved prognosis, however surgery, either liver
      resection or transplantation, remains the mainstay of therapy. An increased
      understanding of liver anatomy, improved imaging modalities and refinements of
      surgical technique have all led to improved outcomes after surgery. Both
      resection and transplantation may be used in a complementary manner. Resection
      remains the treatment of choice for HCC when feasible. Liver transplantation,
      which removes both the tumor and the underlying diseased liver offers excellent
      outcomes in patients that meet the Milan criteria. While both these modalities
      have relatively well defined roles, the treatment of these patients must be
      tailored individually, using a multidisciplinary approach, to maximize survival,
      quality of life and allocation of scarce organs.

PMID- 24894745
TI  - Primary care visits for asthma monitoring over time and association with acute
      asthma visits for urban Medicaid-insured children.
AB  - OBJECTIVES: To examine the association between numbers of primary care provider
      (PCP) visits for asthma monitoring (AM) over time and acute asthma visits in the
      emergency department (ED) and at the PCP for Medicaid-insured children. METHODS:
      We prospectively enrolled 2-10 years old children during ED asthma visits. We
      audited hospital and PCP records for each subject for three consecutive years. We
      excluded subjects also receiving care from asthma subspecialists. PCP AM visits
      were those with documentation that suggested discussion of asthma management but
      no acute asthma symptoms or findings. PCP "Acute Asthma" visits were those with
      documentation of acute asthma symptoms or findings, regardless of treatment. ED
      asthma visits were those with documented asthma treatment. Generalized liner
      models were used to analyze the association between numbers of AM visits and
      acute asthma visits to the ED and PCP. RESULTS: One hundred three subjects were
      analyzed. Over the 3 years, the mean number of AM visits/child was 2.5 +/- 2.3
      (standard deviation), range 0-10. Only 50% of subjects had at least 1 PCP visit
      with an asthma controller medication documented. The mean number of ED asthma
      visits/child was 3.2 +/- 2.8; range 1-18. The mean number of PCP Acute Asthma
      visits/child was 0.7 +/- 1.6; range 0-11. Increasing AM visits was associated
      with more ED visits (estimate 0.088; 95% CI 0.001, 0.174), and more PCP Acute
      Asthma visits (estimate 0.297; 95% CI 0.166, 0.429). Increasing PCP visits for
      any diagnosis was not associated with ED visits (estimate 0.021; 95% CI -0.018,
      0.06). CONCLUSIONS: Asthma monitoring visits and documented controller medication
      for these urban Medicaid-insured children occurred infrequently over 3 years, and
      having more asthma monitoring visits was not associated with fewer ED or PCP
      acute asthma visits.

PMID- 24894747
TI  - (1) H 2D MRSI tissue type analysis of gliomas.
AB  - PURPOSE: To decompose 1H MR spectra of glioma patients into normal and abnormal
      tissue proportions for tumor classification and delineation. METHODS: Anatomical
      imaging and 1H magnetic resonance spectroscopic imaging data have been acquired
      from 11 grade II and 13 grade IV glioma patients. LCModel was used to decompose
      the magnetic resonance spectroscopic imaging data into normal brain, grade II,
      and grade IV tissue proportions using a tissue type basis set. Simulations were
      conducted to evaluate the accuracy of the methodology. Results were visualized
      using colormaps and abnormality contours showing tumor grade and extent. RESULTS:
      Simulations suggest that infiltrative tumor proportions as low as 20% can be
      identified at the typical 1H magnetic resonance spectroscopy signal-to-noise
      found in vivo. Tumor grading according to the highest estimated tumor grade
      within a lesion gave a classification accuracy of 86% discriminating between
      grade II and grade IV glioma. Voxels with significant proportions of tumor type
      spectra were found beyond the margins of contrast enhancement for most grade IV
      cases consistent with infiltration whereas the abnormality contours show that
      some tumors are confined within the hyperintensities shown by both post contrast
      T1 weighted and T2 weighted imaging. CONCLUSION: LCModel can be used to decompose
      1H MR spectra into proportions of normal and abnormal tissue to identify tumor
      extent, infiltration, and overall grade.

PMID- 24894748
TI  - A metoprolol-terbinafine combination induced bradycardia.
AB  - To report a sinus bradycardia induced by metoprolol and terbinafine drug-drug
      interaction and its management. A 63 year-old Caucasian man on metoprolol 200
      mg/day for stable coronary artery disease was prescribed a 90-day course of oral
      terbinafine 250 mg/day for onychomycosis. On the 49th day of terbinafine therapy,
      he was brought to the emergency room for a decrease of his global health status,
      confusion and falls. The electrocardiogram revealed a 37 beats/min sinus
      bradycardia. A score of 7 on the Naranjo adverse drug reaction probability scale
      indicates a probable relationship between the patient's sinus bradycardia and the
      drug interaction between metoprolol and terbinafine. The heart rate ameliorated
      first with a decrease in the dose of metoprolol. It was subsequently changed to
      bisoprolol and the heart rate remained normal. By inhibiting the cytochrome P450
      2D6, terbinafine had decreased metoprolol's clearance, leading in metoprolol
      accumulation which has resulted in clinically significant sinus bradycardia.

PMID- 24894750
TI  - Oxidation of polycyclic aromatic hydrocarbons by horseradish peroxidase in water
      containing an organic cosolvent.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that are
      toxic, mutagenic, and carcinogenic. We investigated the horseradish peroxidase
      (HRP)-catalyzed oxidation of PAHs in water containing N,N-dimethylformamide. Four
      PAHs (anthracene, phenanthrene, pyrene, and fluoranthene) were investigated using
      single-PAH and mixed-PAH systems. The results provide useful information
      regarding the preferential oxidation of anthracene over other PAHs regardless of
      the reaction time, enzyme dosage, and hydrogen peroxide concentration. The
      removal of PAHs was found to be very strongly correlated with the ionization
      potential (IP), and much greater PAH oxidation was observed at a lower IP. The
      oxidation of anthracene was specifically pH- and temperature-dependent, with the
      optimal pH and temperature being 8.0 and 40  degrees C, respectively. The redox
      mediators 1-hydroxybenzotriazole and veratryl alcohol promoted the transformation
      of anthracene by HRP; 9,10-anthraquinone was the main product detected from the
      anthracene oxidation system. The results of this study not only provide a better
      understanding of the oxidation of PAHs by utilizing a plant biocatalyst, but also
      provide a theoretical basis for establishing the HRP-catalyzed treatment of PAH
      contaminated wastewater.

PMID- 24894752
TI  - Response to comment on "distribution features of biological hazardous pollutants
      in residential environments in Korea [Lee et al., Environ Sci Pollut Res (2014)
      21: 1146-1152]".

PMID- 24894749
TI  - Cadmium as a possible cause of bladder cancer: a review of accumulated evidence.
AB  - Bladder cancer is a significant disease, the rates of which have increased over
      the few last years. However, its etiology remains as yet undefined. Cadmium, a
      widespread environmental carcinogen that has received considerable interest,
      presents evidence as a possible cause of bladder cancer. A literature review was
      conducted from the years 1984-2013 to study the accumulated evidence for cadmium
      as a possible cause of bladder cancer, including routes of cadmium exposure,
      accumulation, toxicity, carcinogenicity, and evidence from epidemiological and
      experimental studies. Special reference is devoted to cadmium nephrotoxicity,
      which illustrates how cadmium exerts its effects on the transitional epithelium
      of the urinary tract. Mechanisms of carcinogenesis are discussed. The effects of
      cadmium on gene expression in urothelial cells exposed to cadmium are also
      addressed. Despite different methodologies, several epidemiologic and
      nephrotoxicity studies of cadmium indicate that occupational exposure to cadmium
      is associated with increased risk of bladder cancer and provide additional
      evidence that cadmium is a potential toxic element in urothelial cells. In vitro
      studies provide further evidence that cadmium is involved in urothelial
      carcinogenesis. Animal studies encounter several problems such as morphology
      differences between species. Among the complex mechanisms of cadmium
      carcinogenesis, gene expression deregulation is the subject of recent studies on
      bladder cadmium-induced carcinogenesis. Further research, however, will be
      required to promise a better understanding of the mechanisms underlying cadmium
      carcinogenesis and to establish the precise role of cadmium in this important
      malignancy. 

PMID- 24894753
TI  - Support vector machine-an alternative to artificial neuron network for water
      quality forecasting in an agricultural nonpoint source polluted river?
AB  - Water quality forecasting in agricultural drainage river basins is difficult
      because of the complicated nonpoint source (NPS) pollution transport processes
      and river self-purification processes involved in highly nonlinear problems.
      Artificial neural network (ANN) and support vector model (SVM) were developed to
      predict total nitrogen (TN) and total phosphorus (TP) concentrations for any
      location of the river polluted by agricultural NPS pollution in eastern China.
      River flow, water temperature, flow travel time, rainfall, dissolved oxygen, and
      upstream TN or TP concentrations were selected as initial inputs of the two
      models. Monthly, bimonthly, and trimonthly datasets were selected to train the
      two models, respectively, and the same monthly dataset which had not been used
      for training was chosen to test the models in order to compare their
      generalization performance. Trial and error analysis and genetic algorisms (GA)
      were employed to optimize the parameters of ANN and SVM models, respectively. The
      results indicated that the proposed SVM models performed better generalization
      ability due to avoiding the occurrence of overtraining and optimizing fewer
      parameters based on structural risk minimization (SRM) principle. Furthermore,
      both TN and TP SVM models trained by trimonthly datasets achieved greater
      forecasting accuracy than corresponding ANN models. Thus, SVM models will be a
      powerful alternative method because it is an efficient and economic tool to
      accurately predict water quality with low risk. The sensitivity analyses of two
      models indicated that decreasing upstream input concentrations during the dry
      season and NPS emission along the reach during average or flood season should be
      an effective way to improve Changle River water quality. If the necessary water
      quality and hydrology data and even trimonthly data are available, the SVM
      methodology developed here can easily be applied to other NPS-polluted rivers.

PMID- 24894751
TI  - Distinct diversity of the czcA gene in two sedimentary horizons from a
      contaminated estuarine core.
AB  - In estuarine ecosystems, trace metals are mainly associated with fine grain
      sediments which settle on mudflats. Over time, the layers of sediments accumulate
      and are then transformed by diagenetic processes, recording the history of the
      estuary's chemical contamination. In such a specific environment, we investigated
      to what extent a chronic exposure to contaminants could affect metal-resistant
      sedimentary bacteria in subsurface sediments. The occurrence and diversity of
      cadmium resistance genes (cadA, czcA) was investigated in 5- and 33-year-old
      sediments from a highly contaminated estuary (Seine France). Primers were
      designed to detect a 252-bp fragment of the czcA gene, specifically targeting a
      transmembrane helice domain (TMH IV) involved in the proton substrate antiport of
      this efflux pump. Although the cadA gene was not detected, the highest diversity
      of the sequence of the czcA gene was observed in the 5-year-old sediment.
      According to the percentage of identity at the amino acid level, the closest CzcA
      relatives were identified among Proteobacteria (alpha, beta, gamma, and delta),
      Verrucomicrobia, Nitrospirae, and Bacteroidetes. The most abundant sequences were
      affiliated with Stenotrophomonas. In contrast, in the 33-year-old sediment, CzcA
      sequences were mainly related to Rhodanobacter thiooxydans and Stenotrophomonas,
      suggesting a shaping of the metal-resistant microbial communities over time by
      both diagenetic processes and trace metal contamination.

PMID- 24894754
TI  - Natural and anthropogenic influences on heavy metals in airborne particles over
      the Korean Peninsula.
AB  - Six monitoring stations were selected to characterize the variations in airborne
      concentrations of heavy metals in South Korea between 1999 and 2012. Three
      stations represented higher concentrations, and three represented lower
      concentrations. The heavy metals monitored at these stations include cadmium,
      chromium, copper, iron (Fe), lead, manganese (Mn), and nickel. During the study
      period, concentrations of heavy metals at many stations, including those around
      the Seoul metropolitan area, showed a decreasing trend. However, concentrations
      of Mn and Fe that are primarily of crustal origin increased at four of the six
      stations. Some stations were significantly affected by emissions from the local
      industrial complex (IC), and heavy metal concentrations at those stations were
      relatively high even in summer. Many heavy metal concentrations were higher in
      spring than in winter, but wintertime concentrations of Cr and Pb were higher at
      the stations representing lower concentrations due to the dominant influence of
      combustion emissions. At stations less affected by emissions from the IC,
      concentrations of Fe and Mn that are predominantly crustal in origin were higher
      in spring, when Asian dust (AD) events are most frequent. Although Mn
      concentrations were also high at stations within the steelmaking IC during AD
      periods, they were much higher during non-AD periods due to local emissions.
      Variations in heavy metal concentrations, which are heavily influenced by
      emissions from the IC, warrant individual analysis because their emission
      characteristics differ from those of typical cases. 

PMID- 24894755
TI  - Ballast water treatment systems: design, regulations, and selection under the
      choice varying priorities.
AB  - This paper investigates the role of ballast water treatment systems (BWTSs) and
      proposes a selection procedure for conventional merchant ships based on the
      financial, legal, and operational circumstances. Through the metallurgical
      revolution of the nineteenth century, commercial ships are converted to steel
      hull from wooden structures. By this innovative shift, use of ballast water
      became an essential part of ships for improving propulsion and stability while
      reducing stress on hull (instead of rocks). However, the content of ballast water
      is emerged since it relocates marine species from an ecological composition
      (usually cargo discharging port) to another one (loading port). Uncontrolled
      relocation of marine species may cause severe damage to existing ecological basis
      on ballast discharging area. BWTSs are developed for ships to eliminate marine
      species (i.e., aquatic invasive species) content by using a filtering device. It
      ensures an eco-friendly ballasting and de-ballasting process. The selection of
      proper BWTS is another debate since the BWTSs are designed with cost-quality and
      cost (eco)-performance variations. The proposed approach denoted that both
      tonnage and the age of ship are indicative factors on selection. The cost of
      installation varies based on installation space and active vs. project vessel
      cases. 

PMID- 24894756
TI  - Intra-specific variability in the response of maize to arsenic exposure.
AB  - The response of maize (Zea mays L.) to inorganic arsenic exposure was studied, at
      the seedling stage under hydroponic conditions, preliminarily in sixteen lines
      (fourteen hybrids and two inbred lines) and then, more deeply, in six of these
      lines, selected by showing contrasting differences in their sensitivity to the
      metalloid. The results indicated that (i) maize is rather tolerant to arsenic
      toxicity, (ii) arsenite is more phytotoxic than arsenate, (iii) roots are less
      sensitive than shoots to the metalloid, (iv) a great accumulation of non-protein
      thiols (probably phytochelatins), without substantial effect on the glutathione
      content, is produced in roots but not in shoots of arsenic-exposed plants and (v)
      maize is able to accumulate high levels of arsenic in roots with very low
      translocation to shoots. The study, thus, suggests that maize, for its very low
      rate of acropetal transport of arsenic from roots to shoots, may be a safe crop
      in relation to the risk of entry of metalloid in the food chain and, for being an
      important bioenergy crop capable of expressing high levels of arsenic tolerance
      and accumulation in roots, may represent an interesting opportunity for the
      exploitation of agricultural useless arsenic contaminated lands. 

PMID- 24894757
TI  - Dioxin formation and control in a gasification-melting plant.
AB  - We investigated dioxin formation and removal in a commercial thermal waste
      treatment plant employing a gasification and melting process that has become
      widespread in the last decade in Japan. The aim was to clarify the possibility of
      dioxin formation in a process operation at high temperatures and the
      applicability of catalytic decomposition of dioxins. Also, the possible use of
      dioxin surrogate compounds for plant monitoring was further evaluated. The main
      test parameter was the influence of changes in the amount and type of municipal
      solid waste (MSW) supplied to the thermal waste treatment plant which from day to
      day operation is a relevant parameter also from commercial perspective. Here
      especially, the plastic content on dioxin release was assessed. The following
      conclusions were reached: (1) disturbance of combustion by adding plastic waste
      above the capability of the system resulted in a considerable increase in dioxin
      content of the flue gas at the inlet of the bag house and (2) bag filter
      equipment incorporating a catalytic filter effectively reduced the gaseous dioxin
      content below the standard of 0.1 ng toxic equivalency (TEQ)/m(3) N, by
      decomposition and partly adsorption, as was revealed by total dioxin mass balance
      and an increased levels in the fly ash. Also, the possible use of organohalogen
      compounds as dioxin surrogate compounds for plant monitoring was further
      evaluated. The levels of these surrogates did not exceed values corresponding to
      0.1 ng TEQ/m(3) N dioxins established from former tests. This further
      substantiated that surrogate measurement therefore can well reflect dioxin
      levels.

PMID- 24894761
TI  - Your blues ain't like mine: considering integrative antiracism in HIV prevention
      research with black men who have sex with men in Canada and the United States.
AB  - Evidence-based interventions have been developed and used to prevent HIV
      infections among black men who have sex with men (MSM) in Canada and the United
      States; however, the degree to which interventions address racism and other
      interlocking oppressions that influence HIV vulnerability is not well known. We
      utilize integrative antiracism to guide a review of HIV prevention intervention
      studies with black MSM and to determine how racism and religious oppression are
      addressed in the current intervention evidence base. We searched CINAHL,
      PsychInfo, MEDLINE and the CDC compendium of evidence-based HIV prevention
      interventions and identified seventeen interventions. Three interventions
      targeted black MSM, yet only one intervention addressed racism, religious
      oppression, cultural assets and religious assets. Most interventions' samples
      included low numbers of black MSM. More research is needed on interventions that
      address racism and religious oppression on HIV vulnerability among black MSM.
      Future research should focus on explicating mechanisms by which multiple
      oppressions impact HIV vulnerability. We recommend the development and
      integration of social justice tools for nursing practice that aid in addressing
      the impacts of racism and other oppressions on HIV vulnerability of black MSM. 

PMID- 24894758
TI  - Dioxins in the semen of men with infertility.
AB  - The purpose of the present study was to assess ejaculate contamination by
      polychlorinated dibenzo-p-dioxins/furans in male infertility. The database of 168
      infertile and 49 fertile men was included in the study. Dioxin content was
      determined using gas chromatography/high-resolution mass spectrometry (GC/HRMS).
      In the ejaculate of infertile men, the content of dioxins and furans was 2.2-2.3
      times higher than in fertile donors. The maximum level of the most toxic dioxin
      congener was detected in pathospermia. Contamination of semen of infertile men by
      polychlorinated dibenzo-p-dioxins/furans supports the hypothesis about the
      relationship between environmental factors and reproductive health.

PMID- 24894759
TI  - A step beyond BRET: Fluorescence by Unbound Excitation from Luminescence (FUEL).
AB  - Fluorescence by Unbound Excitation from Luminescence (FUEL) is a radiative
      excitation-emission process that produces increased signal and contrast
      enhancement in vitro and in vivo. FUEL shares many of the same underlying
      principles as Bioluminescence Resonance Energy Transfer (BRET), yet greatly
      differs in the acceptable working distances between the luminescent source and
      the fluorescent entity. While BRET is effectively limited to a maximum of 2 times
      the Forster radius, commonly less than 14 nm, FUEL can occur at distances up to
      um or even cm in the absence of an optical absorber. Here we expand upon the
      foundation and applicability of FUEL by reviewing the relevant principles behind
      the phenomenon and demonstrate its compatibility with a wide variety of
      fluorophores and fluorescent nanoparticles. Further, the utility of antibody
      targeted FUEL is explored. The examples shown here provide evidence that FUEL can
      be utilized for applications where BRET is not possible, filling the spatial void
      that exists between BRET and traditional whole animal imaging.

PMID- 24894762
TI  - Is the rearfoot pattern the most frequently foot strike pattern among
      recreational shod distance runners?
AB  - OBJECTIVE: To determine the distribution of the foot strike patterns among
      recreational shod runners and to compare the personal and training
      characteristics between runners with different foot strike patterns. DESIGN:
      Cross-sectional study. SETTING: Areas of running practice in Sao Paulo, Brazil.
      PARTICIPANTS: 514 recreational shod runners older than 18 years and free of
      injury. OUTCOMES MEASURES: Foot strike patterns were evaluated with a high-speed
      camera (250 Hz) and photocells to assess the running speed of participants.
      Personal and training characteristics were collected through a questionnaire.
      RESULTS: The inter-rater reliability of the visual foot strike pattern
      classification method was 96.7% and intra-rater reliability was 98.9%. 95.1% (n =
      489) of the participants were rearfoot strikers, 4.1% (n = 21) were midfoot
      strikers, and four runners (0.8%) were forefoot strikers. There were no
      significant differences between strike patterns for personal and training
      characteristics. CONCLUSION: This is the first study to demonstrate that almost
      all recreational shod runners were rearfoot strikers. The visual method of
      evaluation seems to be a reliable and feasible option to classify foot strike
      pattern.

PMID- 24894763
TI  - Swiss ball enhances lumbar multifidus activity in chronic low back pain.
AB  - OBJECTIVES: This study examined the effects of sitting surfaces on the cross
      sectional area of lumbar multifidus (LM) in patients with Chronic Low Back Pain
      (CLBP) and healthy controls (HC). DESIGN: Cross-Sectional Case Controlled Study.
      SETTING: Isle of Man Institute of Sport. PARTICIPANTS: 40 age and sex matched,
      sporting participants aged 18-45 years, recruited from private physiotherapy
      practice patients (n = 20 CLBP, 16 male, 4 female, and n = 20 healthy controls,
      16 males and 4 females). MAIN OUTCOME MEASURES: Cross-sectional area of LM was
      measured using rehabilitative ultrasound imaging. RESULTS: Swiss Ball (SB) was
      more effective at stimulating LM than a Stable Surface (SS) in both groups:
      CLBP:SB:12.3 (cm(2)) (SD:3.6), SS:10.15 (SD:2.6), p < 0.0001; HC:SB:12.5
      (SD:2.7), SS:11.3 (SD:2.9), p < 0.0001). No significant differences between
      groups were noted. No differences between left and right side cross-sectional
      areas between or within groups were noted. CONCLUSION: Cross-sectional area of LM
      increased as the lability of the surface increased, demonstrating that SB was
      more effective at stimulating LM activity than a non-labile surface. This
      confirms current clinical practice and supports the use of a labile surface in
      spinal rehabilitation. The lack of LM asymmetry within and between groups is
      discussed.

PMID- 24894764
TI  - Can ultrasound measurements of muscle thickness be used to measure the size of
      individual quadriceps muscles in people with patellofemoral pain?
AB  - OBJECTIVES: Selective atrophy of vastus medialis oblique (VMO) may be present in
      patellofemoral pain (PFP). This study investigated the validity of real-time
      ultrasound in measuring the thickness of each quadriceps muscle. DESIGN: Cross
      sectional-Validity. SETTING: University laboratory. PARTICIPANTS: 10 limbs, 5
      people with unilateral PFP. MAIN OUTCOME MEASURES: The thickness of VMO, vastus
      lateralis (VL), vastus intermedius (VI), rectus femoris (RF), and vastus medialis
      (VM) measured with ultrasound were compared to magnetic resonance imaging (MRI)
      muscle thickness measurements, using Pearson's (r), and compared to MRI muscle
      cross-sectional area (CSA) measurements, using Spearman's correlation coefficient
      (rho). RESULTS: There was a good correlation between ultrasound and MRI measures
      of the thickness of each superficial quadriceps muscle VMO (r = 0.86), VM (r =
      0.86), VL (r = 0.94), RF (r = 0.86), and a poor for VI (r = 0.37). Ultrasound
      measures had a good correlation to MRI muscle CSA measures for VL (rho = 0.83)
      and RF (rho = 0.88), moderate for VM (rho = 0.73), and poor for VMO (rho = 0.20),
      and VI (rho = 0.310). CONCLUSION: Real-time ultrasound muscle thickness
      measurements are correlated to MRI measured thickness of superficial quadriceps
      muscles (VMO, VL, VL, and RF) in PFP.

PMID- 24894765
TI  - Alexithymia is associated with blunted anterior cingulate response to social
      rejection: implications for daily rejection.
AB  - Social rejection elicits distress through the brain's alarm system, the dorsal
      anterior cingulate cortex (dACC). The distress of rejection facilitates
      subsequent inclusion. As a result, traits that blunt this dACC response to social
      rejection might then threaten group membership, leading to further subsequent
      rejection. Alexithymia, the inability to identify and describe affective states,
      is associated with social impairment and reduced dACC activity under conditions
      of negative affect. Thus, we expected that alexithymia would relate to less dACC
      activation during rejection and that this blunted response would explain an
      association between alexithymia and greater rejection in everyday life. Using
      functional magnetic resonance imaging and daily diaries, we found that
      subclinical individual differences in the core feature of alexithymia, difficulty
      identifying affect, was associated with a blunted dACC response to social
      rejection. Deficits in affect identification were also associated with greater
      daily rejection and that this effect was mediated and suppressed by dACC
      activation to rejection. Our findings emphasize the crucial role of the dACC in
      response to social rejection and extend the literature on alexithymia's ability
      to dampen neural responses and contribute to poor social functioning. The
      suppressing role of the dACC suggests future directions for clinical
      interventions on those with affective disorders. 

PMID- 24894767
TI  - Redox self-sufficient whole cell biotransformation for amination of alcohols.
AB  - Whole cell biotransformation is an upcoming tool to replace common chemical
      routes for functionalization and modification of desired molecules. In the
      approach presented here the production of various non-natural (di)amines was
      realized using the designed whole cell biocatalyst Escherichia coli W3110/pTrc99A
      ald-adh-ta with plasmid-borne overexpression of genes for an l-alanine
      dehydrogenase, an alcohol dehydrogenase and a transaminase. Cascading alcohol
      oxidation with l-alanine dependent transamination and l-alanine dehydrogenase
      allowed for redox self-sufficient conversion of alcohols to the corresponding
      amines. The supplementation of the corresponding (di)alcohol precursors as well
      as amino group donor l-alanine and ammonium chloride were sufficient for
      amination and redox cofactor recycling in a resting buffer system. The addition
      of the transaminase cofactor pyridoxal-phosphate and the alcohol dehydrogenase
      cofactor NAD(+) was not necessary to obtain complete conversion. Secondary and
      cyclic alcohols, for example, 2-hexanol and cyclohexanol were not aminated.
      However, efficient redox self-sufficient amination of aliphatic and aromatic
      (di)alcohols in vivo was achieved with 1-hexanol, 1,10-decanediol and
      benzylalcohol being aminated best. 

PMID- 24894766
TI  - Regulating emotion to improve physical health through the amygdala.
AB  - The opinion of mind-body interaction has been increasingly acknowledged in recent
      years, as exemplified by accumulating evidence indicating that physical health
      (body) is associated with emotion and emotion regulation (mind). Yet, the neural
      basis linking emotion regulation with physical health remains largely
      uninvestigated. Here we used magnetic resonance imaging to investigate the neural
      basis of this pathway in a large population of healthy young adults. With a
      systematic study revealing the association of self-reported physical health and
      emotion traits of personality and general affective experiences, we further
      demonstrated that, for better physical health, individuals needed to regulate
      their emotion more effectively. Importantly, individuals who had larger gray
      matter (GM) volume in the amygdala reported not only a higher ability of emotion
      regulation but also better physical health. Further, GM volume in the amygdala
      mediated the correlation between emotion regulation ability and physical health.
      Our findings suggest that the amygdala plays a critical role in the neural
      circuit through which emotion regulation may influence physical health.
      Therefore, our study takes the first step toward exploring the neuroanatomical
      basis for body-mind interaction and may inform interventions aimed at promoting
      physical health by augmenting skills of emotion regulation. 

PMID- 24894768
TI  - Triglyceride-lowering agents.
AB  - This review is the first attempt at systematization of the literature data on the
      structures and activities of triglyceride-lowering agents which used in medical
      practice or are in development. The effects and mechanisms of action of statins,
      squalene synthase inhibitors, fibrates, PPARalpha and PPARalpha/gamma agonists,
      nicotinic acid, omega-3 fatty acids and some other molecular targets were
      considered. Unfortunately, to date, harmless and effective triglyceride-lowering
      drug still does not exist and there is still need for development of better
      triglyceride-lowering agents. 

PMID- 24894769
TI  - Association of both Langerhans cell histiocytosis and Erdheim-Chester disease
      linked to the BRAFV600E mutation.
AB  - Histiocytoses are a group of heterogeneous diseases that mostly comprise
      Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non
      LCH is exceptional. We report 23 patients with biopsy-proven LCH associated with
      Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance
      of this association. We compare the clinical phenotypes of these patients with
      those of 56 patients with isolated LCH and 53 patients with isolated ECD. The
      average age at diagnosis was 43 years. ECD followed (n = 12) or was diagnosed
      simultaneously with (n = 11) but never preceded LCH. Although heterogeneous, the
      phenotype of patients with mixed histiocytosis was closer to that of isolated ECD
      than to that of isolated LCH (principal component analysis). LCH and ECD improved
      in response to interferon alpha-2a treatment in only 50% of patients (8 of 16).
      We found the BRAF(V600E) mutation in 11 (69%) of 16 LCH lesions and in 9 (82%) of
      11 ECD lesions. Eight patients had mutations in both ECD and LCH biopsies. Our
      findings indicate that the association of LCH and ECD is not fortuitous and
      suggest a link between these diseases involving the BRAF(V600E) mutation. 

PMID- 24894770
TI  - ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous
      disease with widely disparate clinical outcomes.
AB  - Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL)
      is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK
      positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic
      and clinical heterogeneity of ALK-negative ALCL has not been delineated. We
      performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK
      negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among
      pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22
      and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These
      rearrangements were mutually exclusive and were absent in ALK-positive ALCLs.
      Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22
      rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3
      genetic markers (P < .0001). Hazard ratios for death in these 4 groups after
      adjusting for International Prognostic Index and age were 1.0 (reference group),
      0.58, 8.63, and 4.16, respectively (P = 7.10 * 10(-5)). These results were
      similar when restricted to patients receiving anthracycline-based chemotherapy,
      as well as to patients not receiving stem cell transplantation. Thus, ALK
      negative ALCL is a genetically heterogeneous disease with widely disparate
      outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as
      predictive biomarkers to help guide patient management.

PMID- 24894771
TI  - Abnormally differentiated CD4+ or CD8+ T cells with phenotypic and genetic
      features of double negative T cells in human Fas deficiency.
AB  - Accumulation of CD3(+) T-cell receptor (TCR)alphabeta(+)CD4(-)CD8(-) double
      negative T cells (DNT) is a hallmark of autoimmune lymphoproliferative syndrome
      (ALPS). DNT origin and differentiation pathways remain controversial. Here we
      show that human ALPS DNT have features of terminally differentiated effector
      memory T cells reexpressing CD45RA(+) (TEMRA), but are CD27(+)CD28(+)KLRG1(-) and
      do not express the transcription factor T-bet. This unique phenotype was also
      detected among CD4(+) or CD8(+) ALPS TEMRA cells. T-cell receptor beta deep
      sequencing revealed a significant fraction of shared CDR3 sequences between ALPS
      DNT and both CD4(+) and CD8(+)TEMRA cells. Moreover, in ALPS patients with a germ
      line FAS mutation and somatic loss of heterozygosity, in whom biallelic mutant
      cells can be tracked by absent Fas expression, Fas-negative T cells accumulated
      not only among DNT, but also among CD4(+) and CD8(+)TEMRA cells. These data
      indicate that in human Fas deficiency DNT cannot only derive from CD8(+), but
      also from CD4(+) T cells. Furthermore, defective Fas signaling leads to aberrant
      transcriptional programs and differentiation of subsets of CD4(+) and CD8(+) T
      cells. Accumulation of these cells before their double-negative state appears to
      be an important early event in the pathogenesis of lymphoproliferation in ALPS
      patients. 

PMID- 24894773
TI  - NrasG12D oncoprotein inhibits apoptosis of preleukemic cells expressing Cbfbeta
      SMMHC via activation of MEK/ERK axis.
AB  - Acute myeloid leukemia (AML) results from the activity of driver mutations that
      deregulate proliferation and survival of hematopoietic stem cells (HSCs). The
      fusion protein CBFbeta-SMMHC impairs differentiation in hematopoietic stem and
      progenitor cells and induces AML in cooperation with other mutations. However,
      the combined function of CBFbeta-SMMHC and cooperating mutations in preleukemic
      expansion is not known. Here, we used Nras(LSL-G12D); Cbfb(56M) knock-in mice to
      show that allelic expression of oncogenic Nras(G12D) and Cbfbeta-SMMHC increases
      survival of preleukemic short-term HSCs and myeloid progenitor cells and
      maintains the differentiation block induced by the fusion protein. Nras(G12D) and
      Cbfbeta-SMMHC synergize to induce leukemia in mice in a cell-autonomous manner,
      with a shorter median latency and higher leukemia-initiating cell activity than
      that of mice expressing Cbfbeta-SMMHC. Furthermore, Nras(LSL-G12D); Cbfb(56M)
      leukemic cells were sensitive to pharmacologic inhibition of the MEK/ERK
      signaling pathway, increasing apoptosis and Bim protein levels. These studies
      demonstrate that Cbfbeta-SMMHC and Nras(G12D) promote the survival of preleukemic
      myeloid progenitors primed for leukemia by activation of the MEK/ERK/Bim axis,
      and define Nras(LSL-G12D); Cbfb(56M) mice as a valuable genetic model for the
      study of inversion(16) AML-targeted therapies. 

PMID- 24894775
TI  - Blood spotlight on Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease affecting people of any
      age, with widely variable clinical manifestations and different outcomes. The
      precise chain of events driving lesional granuloma formation has remained elusive
      for many years. There is evidence for inherited predisposition to and derangement
      of apoptosis and inflammation in lesional dendritic cells. Recently somatic
      BRAF(V600E) mutation in myeloid precursor dendritic cells was associated with the
      more aggressive form of the disease, although the same mutation in a more
      differentiated dendritic cell might drive a less aggressive disease. Whether this
      picture convincingly put LCH in the field of myeloid neoplasm remains to be
      determined. Altogether, these findings suggest that future therapeutic strategy
      might incorporate a screening of this genetic mutation for high-risk patients
      potentially suitable for target therapy.

PMID- 24894774
TI  - The future of autologous stem cell transplantation in myeloma.
AB  - Autologous stem cell transplantation (ASCT) has long been considered frontline
      therapy for newly diagnosed myeloma patients. This Spotlight examines the role of
      ASCT in the era of novel drugs and argues that ASCT should continue to be
      considered for eligible patients. A combination of novel drugs with ASCT in a
      sequential treatment approach can attain long-term survival and perhaps cure a
      subset of patients. ASCT will likely remain an important platform to develop
      curative strategies in the foreseeable future. 

PMID- 24894772
TI  - BMP signaling balances murine myeloid potential through SMAD-independent p38MAPK
      and NOTCH pathways.
AB  - Bone morphogenetic protein (BMP) signaling regulates early hematopoietic
      development, proceeding from mesoderm patterning through the progressive
      commitment and differentiation of progenitor cells. The BMP pathway signals
      largely through receptor-mediated activation of Mothers Against Decapentaplegic
      homolog (SMAD) proteins, although alternate pathways are modulated through
      various components of mitogen-activated protein kinase (MAPK) signaling. Using a
      conditional, short hairpin RNA (shRNA)-based knockdown system in the context of
      differentiating embryonic stem cells (ESCs), we demonstrated previously that
      Smad1 promotes hemangioblast specification, but then subsequently restricts
      primitive progenitor potential. Here we show that co-knockdown of Smad5 restores
      normal progenitor potential of Smad1-depleted cells, suggesting opposing
      functions for Smad1 and Smad5. This balance was confirmed by cotargeting Smad1/5
      with a specific chemical antagonist, LDN193189 (LDN). However, we discovered that
      LDN treatment after hemangioblast commitment enhanced primitive myeloid
      potential. Moreover, inhibition with LDN (but not SMAD depletion) increased
      expression of Delta-like ligands Dll1 and Dll3 and NOTCH activity; abrogation of
      NOTCH activity restored LDN-enhanced myeloid potential back to normal,
      corresponding with expression levels of the myeloid master regulator, C/EBPalpha.
      LDN but not SMAD activity was also associated with activation of the p38MAPK
      pathway, and blocking this pathway was sufficient to enhance myelopoiesis.
      Therefore, NOTCH and p38MAPK pathways balance primitive myeloid progenitor output
      downstream of the BMP pathway. 

PMID- 24894776
TI  - Efficacy of lead-in silibinin and subsequent triple therapy in difficult-to-treat
      HIV/hepatitis C virus-coinfected patients.
AB  - OBJECTIVES: The efficacy of current hepatitis C virus (HCV) triple therapy,
      including a protease inhibitor, is limited in HIV/HCV-coinfected patients with
      advanced liver fibrosis and nonresponse to previous peginterferon-ribavirin.
      These patients have a low chance (only 30%) of achieving a sustained virological
      response (SVR) during triple therapy and cannot wait for next-generation anti-HCV
      drugs. In a pilot study, we investigated the efficacy of a lead-in therapy with
      silibinin before triple therapy in difficult-to-treat patients. METHODS:
      Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and
      documented failure of previous peginterferon-ribavirin treatment. Intervention
      was lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days.
      Subsequently, peginterferon-ribavirin combined with telaprevir was initiated for
      12 weeks, followed by peginterferon-ribavirin dual therapy until week 48 after
      initiation of triple therapy. The outcome measurements were HCV RNA after
      silibinin lead-in, at weeks 2, 4 and 12 of triple therapy, and SVR at week 24
      after the end of treatment. RESULTS: We examined six HIV/HCV-coinfected patients
      (four infected with genotype 1a). All had fibrosis grade METAVIR >=F3 and were on
      fully suppressive antiretroviral therapy. Mean HCV RNA decline after silibinin
      therapy was 2.6 log10 IU/mL (range 2-3 log10 IU/mL). Five of the six patients
      were virologically suppressed at weeks 2 and 4, and all six at week 12 of triple
      therapy. One experienced a viral breakthrough thereafter. Four of five patients
      (80%) showed an SVR 24. One patient had an SVR 12 but has not yet reached week
      24. CONCLUSIONS: A lead-in with silibinin before triple therapy is highly
      effective and increases the probability of HCV treatment success in difficult-to
      treat HIV/HCV-coinfected patients with advanced liver fibrosis and previous
      failure of peginterferon-ribavirin.

PMID- 24894777
TI  - Liver transplantation at KFSHRC: achievement and challenges.
AB  - The liver transplantation program at KFSHRC has been active since 2001. More than
      450 liver transplants have been performed so far. The program evolved from adult
      cadaveric transplant to living donor and recently to pediatric and split
      techniques. The 1-year survival of patients for both pediatric and adult exceeded
      90% and the 5-year survival of patients is more than 80%. Associated with this
      success are challenges that include: organ shortage, quality of organ harvested,
      inability to meet the growing national need, increased demand of resource to meet
      the need of the program, and lack of a collaborative national strategy in organ
      donation and transplantation. 

PMID- 24894778
TI  - Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in
      Arab kindreds.
AB  - BACKGROUND AND OBJECTIVES: L-2-hydroxyglutaric aciduria is a neurometabolic
      disorder with autosomal recessive mode of inheritance in which patients exhibit
      elevated L-2-hydroxyglutaric acid in body fluids, central nervous system
      manifestations, and increased risk of brain tumor formation. Mutations in L2HGDH
      gene have been described in L-2-hydroxyglutaric aciduria patients of different
      ethnicities. The present study was conducted to perform a detailed clinical,
      imaging and genetic analysis. DESIGN AND SETTINGS: A cross-sectional clinical
      genetic study of 16 L-2-hydroxyglutaric aciduria patients from 4 Arab
      consanguineous families examined at the metabolic clinic of the hospital.
      PATIENTS AND METHODS: Genomic DNA was isolated from the blood of 12 patients and
      10 unaffected family members, and the L2HGDH gene was sequenced. DNA sequences
      were compared to the L2HGDH reference sequence from GenBank. RESULTS: All
      patients exhibit characteristic clinical, biochemical, and imaging features of L
      2-hydroxyglutaric aciduria, and 4 patients exhibited increased incidence of brain
      tumors. The sequencing of the L2HGDH gene revealed the c.1015delA, c.1319C > A,
      and c.169G > A mutations in these patients. These mutations encode for the
      p.Arg339AspfsX351, p.Ser440Tyr, and p.Gly57Arg changes in the L2HGDH protein,
      respectively. The c.169G > A mutation, which was shown to have a common origin in
      Italian and Portuguese patients, was also discovered in Arab patients. Finding of
      the homozygous c.159T SNP associated with the c.169G > A mutation in Arab
      patients points to an independent origin of this mutation in Arab population.
      CONCLUSION: The detailed description of clinical manifestations and L2HGDH
      mutation in this study is useful for diagnosis of L-2-hydroxyglutaric aciduria in
      Arab patients. While reoccurrence of an L2HGDH mutation in L-2-hydroxyglutaric
      aciduria patients of different ethnicity is extremely rare, the c.169G mutation
      has an independent origin in Arab patients. It is likely that this mutation may
      also be present in patients of other ethnicities.

PMID- 24894779
TI  - Correlation of clinical efficacy and psychosocial impact on vitiligo patients by
      excimer laser treatment.
AB  - BACKGROUND AND OBJECTIVES: Vitiligo is a difficult disease to treat. Recently, a
      308-nm excimer laser has been shown to be effective in treating vitiligo. In
      addition, the patients with vitiligo have impairment in their quality of life.
      The aim of the study was to investigate the clinical efficacy, safety, and
      psychosocial impact after treating vitiligo with the 308-nm excimer laser. DESIGN
      AND SETTINGS: A prospective clinical trial conducted at dermatology clinics of
      hospitals affiliated with Qassim University, Saudi Arabia, from May 2012 to
      February 2013. PATIENTS AND METHODS: Forty-eight patients with 105 vitiliginous
      patches were treated using a 308-nm excimer laser. The treatment was performed
      twice per week for a maximum of 48 treatments or 100% repigmentation of lesions
      whichever was achieved first. The assessment of the clinical response and
      recording of side effects were performed biweekly. RESULTS: Out of 105 lesions in
      these patients, 63 lesions (60.0%) achieved over 75% repigmentation by laser
      treatment, 12 lesions (11.4%) showed 51% to 75% repigmentation, 9 lesions (8.6%)
      showed 26% to 50% repigmentation, and another 9 lesions (8.6%) showed 1% to 25%
      repigmentation, while 12 lesions (11.4%) showed no repigmentation. The average
      (+/-standard deviation [SD]) number of sessions needed to achieve repigmentation
      was 16.8 (8.0), whereas the average (+/-SD) number of sessions needed to realize
      Grade IV repigmentation was 20.2 (15). The type of repigmentation varied between
      lesions. Diffuse repigmentation was the most common pattern and occurred in 34
      lesions (36.6%). Facial lesions responded better than lesions located elsewhere.
      Skin type did not play a statistically significant role (P=.07) in the lesions
      response to treatment. All side effects were mild and disappeared shortly after
      end of treatment sessions. CONCLUSION: The clinical data indicate that the
      treatment of vitiligo using the 308-nm excimer laser is effective and safe and
      improves psychosocial quality of life. Lesion location, duration of disease, and
      treatment duration are factors affecting the clinical and psychological outcome.

PMID- 24894780
TI  - Overproduction of CXC chemokines CXCL1, CXCL9, CXCL10 and CXCL12 in beta
      thalassemia major or patients.
AB  - BACKGROUNDS AND OBJECTIVES: B-thalassemia major is one of the most frequent
      hematological genetic disorders, worldwide. Chemokines are the main components of
      the immune system and play fundamental roles in pathogenesis of inflammatory
      disorders. Therefore, the present study aimed to examine whether serum CXC
      chemokines are altered in b-thalassemia major patients. DESIGN AND SETTINGS: We
      enrolled 63 b-thalassemia patients and 80 controls in this cross-sectional study,
      which was performed during 2012-2013 in Kerman, Iran. METHODS: We enrolled 63 b
      thalassemia patients and 80 controls in the present study. Patients were selected
      from referrals to Samenolhojaj clinic for thalassemia, Kerman, Iran. The
      circulating levels of CXCL1, CXCL9, CXCL10, and CXCL12 were detected by enzyme
      linked immunosorbent assay in thalassemia patients and healthy controls
      immediately after blood collection. Data were analyzed by c2, t-test, and
      analysis of variance statistical methods and using SPSS, version 13 (SPSS Inc.,
      Chicago, IL). RESULTS: The results of the study demonstrated a significant
      elevation of CXCL1, CXCL9, CXCL10, and CXCL12 in thalassemia patients than in
      control. These results also demonstrated that serum chemokine levels are related
      to transfusion duration and post-transfusion viral infections. CONCLUSION:
      According to the results obtained, it can probably be concluded that chemokines
      are also involved in the pathogenesis of b-thalassemia major and its clinical
      complications in addition to several other parameters.

PMID- 24894781
TI  - Medical students preference of problem-based learning or traditional lectures in
      King Abdulaziz University, Jeddah, Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Problem-based learning (PBL) is the most important
      educational innovations in the past 4 decades. The objective of the study was to
      compare between the preference of medical students for PBL and the preference for
      traditional lectures regarding learning outcomes (e.g., knowledge, attitude, and
      skills) gained from both methods. DESIGN AND SETTINGS: A cross-sectional study
      was conducted among medical students who studied the hybrid curriculum (PBL and
      traditional lectures) in King Abdulaziz University, Jeddah, in 2011. METHODS:
      Data was collected through a pre-constructed, validated, confidentially
      anonymous, and self-administered questionnaire. Students' perceptions toward PBL
      and traditional lectures were assessed through their response to 20 statements
      inquired about both methods of learning using a five-point Likert scale.
      Descriptive and analytic statistics were performed using SPSS, version 21 (SPSS
      Inc, Chicago, Ill., USA). RESULTS: Learners preferred PBL more to traditional
      lectures for better linking the knowledge of basic and clinical sciences (t
      test=10.15, P < .001). However, no statistical significant difference (P > .05)
      was observed regarding the amount of basic knowledge recalled from both methods.
      Students preferred PBL more to lectures for better learning attitudes, skills,
      future outcomes, and learning satisfaction (P < .05). PBL motivates students to
      learn better than lecturing (P < .05). From students' opinion, the mean total
      skill gained from PBL (47.2 [10.6]) was much higher than that of lectures (33.0
      [9.9]), and a highly statistical significant difference was observed (t
      test=20.9, P < .001). CONCLUSION: Students preferred PBL more to traditional
      lectures for improving most of learning outcome domains, especially, learning
      attitudes and skills. Introducing hybrid-PBL curriculum in all Saudi universities
      is highly recommended.

PMID- 24894782
TI  - Distribution of ideal cardiovascular health in a community-based cohort of Middle
      East population.
AB  - BACKGROUND AND OBJECTIVES: To improve cardiovascular (CV) health of American
      population, the American Heart Association (AHA) developed definitions of ideal,
      intermediate, and poor CV health based on 7 accessible health metrics. The
      applicability of this construct and the distribution of its components in the
      community-based populations in the Middle East region have not been reported.
      DESIGN AND SETTINGS: A prospective population-based cohort study conducted from
      1999 to 2011. METHODS: We used data from phase 4 of Tehran Lipid and Glucose
      Study (2009-2011) (2861 women and 2004 men, aged >= 20 years) to estimate the
      frequency of CV health levels (ideal, intermediate, and poor) in adults of both
      genders, and the frequency of each metric at each level of CV health. The median
      or mean of each CV health metric was also estimated in the whole spectrum of CV
      health in all subgroups. RESULTS: Only 1 adult participant met all 7 ideal CV
      health metrics; 25.01% of women and 26% of men had intermediate CV health; 74.8%
      of women and 74% of men exhibited poor CV health. Only 19.7% of women and 10.3%
      of men had 5 or more ideal CV health metrics. Nonsmoking was the most frequent
      ideal health behavior. A total of 89.6% of participants had 1 or 2 ideal CV
      health behaviors. Ideal smoking and fasting plasma glucose had the highest
      frequency of CV health factors among others. CONCLUSION: The frequency of ideal
      CV health was extremely low in this cohort of adults. The frequency of
      intermediate CV health was also low, and it may be significantly lower in the
      general population.

PMID- 24894783
TI  - Visceral leishmaniasis-hepatitis B/C coinfections: a rising necessity to triage
      patients for treatment.
AB  - BACKGROUND AND OBJECTIVES: Visceral leishmaniasis (VL) is a life-threatening
      infection caused by Leishmania species. In Sudan, VL is caused by L donovani.
      Most drugs used to treat VL, especially pentavalent antimony compounds (sodium
      stibogluconate, SSG), are potentially hepatotoxic. A number of fatal catastrophes
      happened because patients with VL-hepatitis B/C coinfection were indiscriminately
      treated with SSG in settings where VL and viral hepatitis coexist. This study
      aimed to study biochemical and hematological parameters of patients with VL
      hepatitis B/C coinfections with the aim to modify treatment protocols to reduce
      coinfection.added morbidity and mortality. DESIGN AND SETTINGS: This was a
      prospective analytical, hospital-based, and case-controlled study. The study was
      done at Kassab Hospital and Professor Elhassan Centre for tropical medicine
      during the period of February 2008 to April 2013. MATERIALS AND METHODS:
      Following informed consent by the participants, 78 parasitologically confirmed VL
      patients with either hepatitis B or C or both and 528 sex- and age-unmatched VL
      patients without hepatitis B/C coinfection (control group) were enrolled
      sequentially. Diagnosis of hepatitis B or C was made using immunochromatographic
      test kits and confirmed by an enzyme-linked immunosorbent assay. RESULTS: VL
      patients with hepatitis B/C coinfections had significantly increased levels of
      AST, ALT, and total bilirubin compared to the control group (P=.0001 for all),
      with significantly decreased levels of albumin and platelets counts (P=.0029 for
      both). CONCLUSION: VL-hepatitis B/C coinfections are an emerging entity that
      needs anti-leishmanial treatment modification. Alternative treatments like
      paromomycin and amphotericin B (AmBisome) could be reserved for these patients.

PMID- 24894784
TI  - Consanguinity and isolated atrial septal defect in North East of Iran.
AB  - BACKGROUND AND OBJECTIVES: The rate of consanguineous marriage is high in Middle
      Eastern countries such as Iran. The relationship between consanguineous marriage
      and congenital heart disease is discussed in some studies, but there is not much
      data for relationship between atrial septal defect (ASD) and consanguineous
      marriage. The aim of this study was to evaluate the relationship between
      consanguineous marriage and ASD echocardiographic characteristics. DESIGN AND
      SETTINGS: This was a cross-sectional study approved by Mashhad University of
      Medical Sciences ethics committee and took place in Mashhad, Iran, for a period
      of 3 years from August 2008 till September 2011. METHODS: In this cross-sectional
      study, 113 ASD patients participated and they were categorized into 3 groups on
      the basis of family relationship between their parents: first group-"no
      relationship," second group- "third degree relationship," and third group- "far
      relationship." RESULTS: Among the 54 male and 59 female ASD patients, the most
      prevalent type of ASD was ASD secundum (85.0%) followed by sinus venosus (8.8%).
      A total of 56% patients were present in the first group and 15% and 29% in the
      second group and the third group, respectively." The relationship between
      consanguinity and type of ASD (P < .001) and gender (P < .001 each) was observed.
      The relationship between the age of onset of disease and consanguinity (P=.003)
      was also observed. CONCLUSION: Considering the fact that there is a high
      prevalence of ASD and consanguineous marriage in Iran and bearing in mind the
      results of the present study, we recommend educating couples about the outcomes
      of consanguineous marriage in pre-marriage counseling.

PMID- 24894785
TI  - Toward malaria eradication in Saudi Arabia: evidence from 4-year surveillance in
      Makkah.
AB  - BACKGROUND AND OBJECTIVES: Saudi Arabia has implemented strategies for the
      eradication of malaria. However, influx of people from countries endemic for
      malaria for either employment or Hajj makes the country highly susceptible to
      malaria importation. The Makkah region is known to host millions of immigrants
      yearly and has a surveillance system to monitor the incidence of malaria. The
      objective of this study was to examine malaria patients, nationality, and
      parasite type in Makkah region between 2008 and 2011. DESIGN AND SETTINGS: A
      retrospective analysis of all reported malaria cases from 19 sentinel sites in
      Makkah region, Saudi Arabia, for the period between 2008 and 2011. METHODS:
      Analysis of surveillance data were analyzed using SPSS software, version 15.0
      (SPSS Inc, Chicago). RESULTS: A total of 318 malaria cases were reported in these
      4 years, of which only 3.6% of cases were less than 10 years of age, including 2
      cases below 5 years. Non-Saudis were 95% and Pakistanis, Nigerians, and Indians
      accounted for 62.0%. Plasmodium falciparum (67%). Plasmodium vivax (32%) and
      Plasmodium ovale (1.6%) were the notable parasites. CONCLUSION: The low frequency
      of malaria in Makkah suggests that Saudi Arabia is in the consolidation phase of
      malaria eradication. The absence of local transmission of malaria is indicated by
      low frequency of malaria in children less than 5 years of age, and high frequency
      of malaria in non-Saudis is evidence of malaria importation. Health workers
      attending to foreigners with febrile illness from Pakistan, Nigeria, and India
      should consider malaria as their first line of suspicion.

PMID- 24894786
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for managing
      peritoneal carcinomatosis from endometrial carcinoma: a single-center experience
      of 6 cases.
AB  - BACKGROUND AND OBJECTIVES: Endometrial carcinoma is the most common gynecologic
      malignancy worldwide. Prognosis of patients with peritoneal carcinomatosis (PC)
      from endometrial carcinoma is deadly, with an estimated median survival not
      exceeding 12 months. The objective of this study was to report our experience
      with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy
      (HIPEC) for managing PC from primary and recurrent endometrial carcinoma. DESIGN
      AND SETTINGS: A retrospective analysis of 6 patients with PC arising from
      endometrial cancer, who were managed with CRS and HIPEC at our referral tertiary
      care center, from November 2010 to August 2013. MATERIALS AND METHODS: Six
      patients underwent CRS and HIPEC. CRS was performed using standard peritonectomy
      procedures and visceral resections directed toward the complete elimination of
      tumors from ab.dominopelvic cavity. HIPEC was performed with cisplatin (50 mg/m2)
      and doxorubicin (15 mg/m2) and allowed to circulate in abdominopelvic cavity for
      90 minutes at 41.0 to 42.2 degrees C. RESULTS: Two patients with primary
      endometrial carcinoma and 4 patients with recurrent endometrial carcino.ma
      confined to peritoneal cavity were studied. Complete cytoreduction (CC-0) was
      achieved in 5 patients. The International Federation of Gynecology and Obstetrics
      (FIGO) stages and histopathological types were as follows: IB endometrioid
      adenocarcinomas (n=1), IC mesonephric carcinomas (n=1), IIIA endometrioid
      adenocarcino.mas (n=2), IIIA papillary serous carcinomas (n=1), and IIIC clear
      cell carcinomas (n=1). Anastomotic leak (grade I) was the most commonly
      encountered postoperative complication. Two patients developed grade IV
      compli.cations due to septicemia and pulmonary embolism. No intraoperative
      mortality occurred. Postoperatively, all patients received chemotherapy
      (carboplatin and paclitaxel). In 1 patient, the clear-cell carcinoma histologic
      lesion relapsed within 6 months; the metastases spread to hepatic, pelvic, and
      mesenteric lymph nodes, and the patient died 5 months later. One patient with
      cytoreduction completeness of CC-2 developed hepatic metastases within 3 months
      and is still alive at a follow-up up 6 months. Remaining patients (n=4) are alive
      and disease free without evidence of recurrence of follow-ups at 35, 34, 19, and
      7 months. CONCLUSION: CRS and HIPEC are well-tolerated and feasibly promising
      management modalities in PC from primary and recurrent endometrial carcinoma.
      Further research is needed for in-depth analysis.

PMID- 24894787
TI  - Cochlear implant for bilateral profound sensorineural hearing loss in an
      adolescent with sickle cell anemia.
AB  - We present the first-published cochlear implant in an adolescent with sickle cell
      anemia (SCA) and bilateral profound sensorineural hearing loss (SNHL). A 15-year
      old Saudi girl, previously diagnosed with SCA, developed gradual bilateral
      permanent profound SNHL over 18 months and underwent a successful cochlear
      implantation. SNHL associated with sickle cell crises is a well-known phenomenon.
      Regular hearing assessments are recommended for sickle cell patients, and early
      referrals for cochlear implantations are advocated for those with permanent
      profound SNHL. 

PMID- 24894788
TI  - Transcatheter closure of residual postinfarction ventricular septal defect after
      dehiscence of surgical patch repair.
AB  - Ventricular septal defect (VSD) is a life-threatening complication of transmural
      myocardial infarction. Urgent surgical repair and concomitant revascularization
      are the standard of care. Percutaneous catheter-based closure techniques have
      been reserved for patients with a high-risk surgery or a failed surgical
      procedure with residual shunting. This case report demonstrates the successful
      transcatheter closure of residual VSD using the Amplatzer muscular VSD device
      (Amplatzer, Minnesota, USA) after surgical patch dehiscence for postinfarction
      VSD and 3-and-a-half years' post-intervention follow-up. 

PMID- 24894789
TI  - A novel MPV17 gene mutation in a Saudi infant causing fatal progressive liver
      failure.
AB  - We describe in this report the clinical, biochemical, and molecular features of a
      Saudi infant with hepatocerebral MDS secondary to a novel homozygous mutation in
      the MPV17 gene. An automated sequencing of the nuclear MPV17 gene was performed.
      The coding region (7 exons) of the MPV17 gene was amplified using an M13-tagged
      intronic primer and screened by direct sequencing of the PCR-amplified products
      (GenBank Association Number NM_002437.4). The sequencing of the entire coding
      region and intron-exon boundaries of MPV17 gene revealed a single homozygous
      variant, -c.278A > C(p.Q93P), which predicts the substitution of a highly
      conserved amino acid. This particular sequence variant has not been previously
      reported as a single-nucleotide polymorphism (SNP) or pathogenic mutation.
      Diagnostic workup for neonatal liver disorders should include mutation screening
      for known genes. The new advances in molecular genetics can help clinicians
      establish the diagnosis in a timely fashion, which may prevent a child from
      undergoing invasive and expensive investigations. 

PMID- 24894790
TI  - Pseudo-Kaposi sarcoma worsening after leg vein harvest for coronary artery bypass
      grafting.
AB  - Acroangiodermatitis (AAD) (synonym, pseudo-Kaposi sarcoma) is a term that
      encompasses 2 different conditions: (1) AAD of Mali, which refers to skin lesions
      that mainly develop bilaterally on the lower extremities of patients with chronic
      venous insufficiency and is an extreme form of stasis dermatitis and (2) Stewart
      Bluefarb syndrome, which consists of an arteriovenous malformation that mainly
      affects the limbs of young patients unilaterally. We present a case of a 68-year
      old lady with progressive skin lesions on both lower limbs (right > left) as a
      result of chronic venous insufficiency that became worse after the leg-vein
      harvest for coronary artery bypass grafting was taken from the right leg. Up to
      our knowledge this is the first case of its kind to be reported. 

PMID- 24894791
TI  - Cutaneous composite hemangioendothelioma: case report and review of published
      reports.
AB  - Composite hemangioendothelioma (CHE) is a rare, locally aggressive, vascular
      tumor of intermediate-/ low-grade malignancy, and is characterized by varying
      combinations of benign, low-grade malignant, and malignant vascular components.
      In cutaneous localization, only 22 cases have been reported so far. A new case of
      CHE of the gluteal region in a 58-year-old man is described. Microscopically,
      vascular neoplasm, situated mainly within the deep dermis and the subcutaneous
      fat tissue, was composed of sinusoidal hemangioma, arteriovenous hemangioma,
      retiform hemangioendothelioma (RHE), and angiosarcoma. An average number of
      mitoses within the angiosarcomatous component was 10 per 10 high-power fields.
      Immunohistochemically, the tumor cells were positive for factor VIII-related
      antigen, CD34, and CD31 and negative for D2-40 and GLUT-1. Ki-67 labeling index
      was 21%, 1.2%, and 0% in the areas of angiosarcoma, RHE, and sinusoidal
      hemangioma, respectively. No recurrent disease was noted 3 months after the
      surgery. The present case displayed the following features previously undescribed
      in CHE: a novel component of sinusoidal hemangioma and localization at the
      gluteal region. We also provide review of clinical, histopathological, and
      immunohistochemical characteristics of cutaneous CHE from the published cases. 

PMID- 24894792
TI  - Severe hypoglycemia as a presenting feature of aluminum phosphide poisoning.

PMID- 24894793
TI  - Re: oligoarticular juvenile idiopathic arthritis among Saudi children.

PMID- 24894794
TI  - Re: steroid-resistant nephrotic syndrome: impact of genetic testing.

PMID- 24894795
TI  - Histochemical staining of Arabidopsis thaliana secondary cell wall elements.
AB  - Arabidopsis thaliana is a model organism commonly used to understand and
      manipulate various cellular processes in plants, and it has been used extensively
      in the study of secondary cell wall formation. Secondary cell wall deposition
      occurs after the primary cell wall is laid down, a process carried out
      exclusively by specialized cells such as those forming vessel and fiber tissues.
      Most secondary cell walls are composed of cellulose (40-50%), hemicellulose (25
      30%), and lignin (20-30%). Several mutations affecting secondary cell wall
      biosynthesis have been isolated, and the corresponding mutants may or may not
      exhibit obvious biochemical composition changes or visual phenotypes since these
      mutations could be masked by compensatory responses. Staining procedures have
      historically been used to show differences on a cellular basis. These methods are
      exclusively visual means of analysis; nevertheless their role in rapid and
      critical analysis is of great importance. Congo red and calcofluor white are
      stains used to detect polysaccharides, whereas Maule and phloroglucinol are
      commonly used to determine differences in lignin, and toluidine blue O is used to
      differentially stain polysaccharides and lignin. The seemingly simple techniques
      of sectioning, staining, and imaging can be a challenge for beginners. Starting
      with sample preparation using the A. thaliana model, this study details the
      protocols of a variety of staining methodologies that can be easily implemented
      for observation of cell and tissue organization in secondary cell walls of
      plants. 

PMID- 24894798
TI  - Red cell distribution width in organophosphate insecticide poisoning: utility or
      futility?

PMID- 24894797
TI  - Plum and soy aglycon extracts superior at increasing bone calcium retention in
      ovariectomized Sprague Dawley rats.
AB  - Plant-derived polyphenols have been shown to influence bone turnover and bone
      properties in the estrogen-depleted state. We used a crossover design in
      ovariectomized rats (n = 16 rats for each diet) to investigate the effect of
      supplementation of two doses each of blueberry, plum, grape, grape seed extract,
      and resveratrol on bone. We tested the aglycon and glucoside forms of genistein
      to quantify differences in efficacy on bone calcium retention. Rats were given an
      intravenous dose of 45Ca to prelabel bone, and bone calcium retention was
      assessed by urinary excretion of 45Ca:Ca ratio during an intervention period
      compared with nonintervention. Genistein aglycon increased bone calcium retention
      significantly (p<0.05) more than the glucoside (22% vs 13%, respectively). Plum
      extract (0.45% w/w total dietary polyphenols) and resveratrol (0.2% w/w total
      dietary polyphenols) were also effective, increasing bone calcium retention by
      20% (p=0.0153) and 14% (p=0.0012), respectively. Several polyphenolic-rich diets
      improved bone calcium retention.

PMID- 24894799
TI  - Oxidative damage impact on aging and age-related diseases: drug targeting of
      telomere attrition and dynamic telomerase activity flirting with imidazole
      containing dipeptides.
AB  - It has been documented that telomere-associated cellular senescence may
      contribute to certain age-related disorders, including an increase in cancer
      incidence, wrinkling and diminished skin elasticity, atherosclerosis,
      osteoporosis, weight loss, age-related cataract, glaucoma and others. Shorter
      telomere length in leukocytes was associated crosssectionally with cardiovascular
      disorders and their risk factors, including pulse pressure and vascular aging,
      obesity, vascular dementia, diabetes, coronary artery disease, myocardial
      infarction (although not in all studies), cellular turnover and exposure to
      oxidative and inflammatory damage in chronic obstructive pulmonary disease. It
      has been proposed that telomere length may not be a strong biomarker of survival
      in older individuals, but it may be an informative biomarker of healthy aging.
      The data reveal that telomere dynamics and changes in telomerase activity are
      consistent elements of cellular alterations associated with changes in
      proliferative state and in this article these processes are consequently
      considered as the new therapeutic drug targets for physiological control with
      advanced drug delivery and nutritional formulations. In particular, the presence
      of highly specific correlations and early causal relationships between telomere
      loss in the absence of telomerase activity and replicative senescence or crisis,
      and from the other side, telomerase reactivation and cell immortality, point to
      new and important treatment strategies or the therapeutic manipulation during
      treatment of age related disorders and cancer. Once better controls and
      therapeutic treatments for aging and age-related disorders are achieved, cellular
      rejuvenation by manipulating telomeres and enzyme telomerase activity may reduce
      some of the physiological declines that accompany aging. In this work, we raise
      and support a therapeutic concept of using non-hydrolyzed forms of naturally
      occurring imidazoledipeptide based compounds carnosine and carcinine, making it
      clinically possible that slowing down the rate of telomere shortening could slow
      down the human aging process in specific tissues where proliferative senescence
      is known to occur with the demonstrated evidence of telomere shortening appeared
      to be a hallmark of oxidative stress and disease. The preliminary longitudinal
      studies of elderly individuals suggest that longer telomeres are associated with
      better survival and an advanced oral nutritional support with non-hydrolyzed
      carnosine (or carcinine and patented compositions thereof) and patented N
      acetylcarnosine lubricant eye drops are useful therapeutic tools of a critical
      telomere length maintenance that may fundamentally be applied in the treatment of
      age-related sight-threatening eye disorders, prolong life expectancy, increase
      survival and chronological age of an organism in health control, smoking behavior
      and disease. 

PMID- 24894800
TI  - Effect of solvent environment on colloidal-quantum-dot solar-cell
      manufacturability and performance.
AB  - The absorbing layer in state-of-the-art colloidal quantum-dot solar cells is
      fabricated using a tedious layer-by-layer process repeated ten times. It is now
      shown that methanol, a common exchange solvent, is the main culprit, as extended
      exposure leaches off the surface halide passivant, creating carrier trap states.
      Use of a high-dipole-moment aprotic solvent eliminates this problem and is shown
      to produce state-of-the-art devices in far fewer steps. 

PMID- 24894801
TI  - Just say 'know': how do cannabinoid concentrations influence users' estimates of
      cannabis potency and the amount they roll in joints?
AB  - AIMS: (1) To determine whether measured concentrations of delta-9
      tetrahydrocannabinol (THC) and cannabidiol (CBD) in individuals' own cannabis
      predict their estimates of drug potency and actual titration; and (2) to
      ascertain if these effects are influenced by frequency of use and cannabis type.
      DESIGN: Cross-sectional, naturalistic. SETTING: Participants' own homes.
      PARTICIPANTS: A total of 247 cannabis users in the United Kingdom: 152
      'recreational' (1-24 days/month) and 95 'daily' (>=25 days/month). METHODS:
      Participants rated their own cannabis for its potency (1-10) and type ('resin',
      'herbal', 'skunk') before smoking it in front of the researcher. The amount of
      cannabis (g) used in their joints was recorded and an additional sample was
      analysed for THC and CBD concentrations (%). FINDINGS: THC concentrations were
      related negatively to the amount of cannabis used [unstandardized regression
      coefficient: b = -0.009, 95% confidence interval (CI) = -0.017, -0.002]. Potency
      estimates were predicted by increasing THC (b = 0.055, 95% CI = 0.020, 0.090) and
      decreasing CBD (b = -0.160, 95% CI = -0.284, -0.062), and both of these
      associations were mediated by cannabis type (THC: b = 0.018, 95% CI = 0.006,
      0.037; CBD: b = -0.105, 95% CI = -0.198, -0.028). Potency estimates were more
      reflective of THC as frequency of use increased (b = 0.004, 95% CI = 0.001,
      0.007) and were 7.3 times more so in daily (partial r = 0.381) than recreational
      users (r = 0.052). CONCLUSIONS: When using their own cannabis in a naturalistic
      setting, people titrate the amount they roll in joints according to
      concentrations of delta-9-tetrahydrocannabinol (THC) but not cannabidiol (CBD).
      Recreational users thus show poor understanding of cannabis potency.

PMID- 24894802
TI  - DSM-5 and ICD-11 definitions of posttraumatic stress disorder: investigating
      "narrow" and "broad" approaches.
AB  - BACKGROUND: The development of the Diagnostic and Statistical Manual of Mental
      Disorders 5th edition (DSM-5) and ICD-11 has led to reconsideration of diagnostic
      criteria for posttraumatic stress disorder (PTSD). The World Mental Health (WMH)
      Surveys allow investigation of the implications of the changing criteria compared
      to DSM-IV and ICD-10. METHODS: WMH Surveys in 13 countries asked respondents to
      enumerate all their lifetime traumatic events (TEs) and randomly selected one TE
      per respondent for PTSD assessment. DSM-IV and ICD-10 PTSD were assessed for the
      23,936 respondents who reported lifetime TEs in these surveys with the fully
      structured Composite International Diagnostic Interview (CIDI). DSM-5 and
      proposed ICD-11 criteria were approximated. Associations of the different
      criteria sets with indicators of clinical severity (distress-impairment,
      suicidality, comorbid fear-distress disorders, PTSD symptom duration) were
      examined to investigate the implications of using the different systems. RESULTS:
      A total of 5.6% of respondents met criteria for "broadly defined" PTSD (i.e.,
      full criteria in at least one diagnostic system), with prevalence ranging from
      3.0% with DSM-5 to 4.4% with ICD-10. Only one-third of broadly defined cases met
      criteria in all four systems and another one third in only one system (narrowly
      defined cases). Between-system differences in indicators of clinical severity
      suggest that ICD-10 criteria are least strict and DSM-IV criteria most strict.
      The more striking result, though, is that significantly elevated indicators of
      clinical significance were found even for narrowly defined cases for each of the
      four diagnostic systems. CONCLUSIONS: These results argue for a broad definition
      of PTSD defined by any one of the different systems to capture all clinically
      significant cases of PTSD in future studies.

PMID- 24894807
TI  - Development of polar order and tilt in lamellar liquid crystalline phases of a
      bent-core mesogen.
AB  - A new bent-core mesogen combining a 4-cyanoresorcinol unit with two terephthalate
      based rod-like wings and terminated by two long alkyl chains, was synthesized and
      investigated by DSC, XRD, optical, electrooptical and dielectric methods. A
      series of liquid crystalline phases in the unique sequence SmA-SmA(P)-SmCPR
      (M1/SmCPalpha)-SmCsPA-SmCPA-SmCaPA, mainly distinguished by the degree and mode
      of correlation of tilt and polar order, was observed. The development of polar
      order is associated with the emergence of a small tilt (<10 degrees ). With
      decreasing temperature the tilt changes from random (SmA) via synclinic to
      anticlinic, while the coherence length of the polar domains grows. This small
      tilt gives rise to an only weak layer coupling which is in competition with the
      polar coupling and this leads to new modes of self assembly in lamellar phases of
      bent-core mesogens, among them the SmCPR and the SmCPalpha phases. The SmCPR
      phase is an only slightly tilted biaxial smectic phase with randomized polar
      order and the SmCPalpha phase is a slightly tilted and antiferroelectric
      switching, but uniaxial smectic phase. For this phase a regular change of the in
      plane polarization vector between the layers by an angle between >0 degrees  and
      <90 degrees  is proposed. 

PMID- 24894805
TI  - Orbitofrontal neurons infer the value and identity of predicted outcomes.
AB  - The best way to respond flexibly to changes in the environment is to anticipate
      them. Such anticipation often benefits us if we can infer that a change has
      occurred, before we have actually experienced the effects of that change. Here we
      test for neural correlates of this process by recording single-unit activity in
      the orbitofrontal cortex in rats performing a choice task in which the available
      rewards changed across blocks of trials. Consistent with the proposal that
      orbitofrontal cortex signals inferred information, firing changes at the start of
      each new block as if predicting the not-yet-experienced reward. This change
      occurs whether the new reward is different in number of drops, requiring
      signalling of a new value, or in flavour, requiring signalling of a new sensory
      feature. These results show that orbitofrontal neurons provide a behaviourally
      relevant signal that reflects inferences about both value-relevant and value
      neutral information about impending outcomes. 

PMID- 24894808
TI  - Microscopy and microanalysis of complex nanosized strengthening precipitates in
      new generation commercial Al-Cu-Li alloys.
AB  - Precipitates (ppts) in new generation aluminum-lithium alloys (AA2099 and AA2199)
      were characterised using scanning and transmission electron microscopy and atom
      probe tomography. Results obtained on the following ppts are reported: Guinier
      Preston zones, T1 (Al2 CuLi), beta' (Al3 Zr) and delta' (Al3 Li). The focus was
      placed on their composition and the presence of minor elements. X-ray energy
      dispersive spectrometry in the electron microscopes and mass spectrometry in the
      atom probe microscope showed that T1 ppts were enriched in zinc (Zn) and
      magnesium up to about 1.9 and 3.5 at.%, respectively. A concentration of 2.5 at.%
      Zn in the delta' ppts was also measured. Unlike Li and copper, Zn in the T1 ppts
      could not be detected using electron energy-loss spectroscopy in the transmission
      electron microscope because of its too low concentration and the small sizes of
      these ppts. Indeed, Monte Carlo simulations of EEL spectra for the Zn L2,3 edge
      showed that the signal-to-noise ratio was not high enough and that the detection
      limit was at least 2.5 at.%, depending on the probe current. Also, the simulation
      of X-ray spectra confirmed that the detection limit was exceeded for the Zn
      Kalpha X-ray line because the signal-to-noise ratio was high enough in that case,
      which is in agreement with our observations. 

PMID- 24894809
TI  - Layer-by-layer films as biomaterials: bioactivity and mechanics.
AB  - Layer-by-layer (LbL) assembly offers a facile approach toward biomaterials of
      nanoscale thickness. Bioactivity may be realized through incorporation of
      biomolecular species within the film architecture, and film mechanics may be
      controlled through post-formation chemical cross-linking steps. This short review
      focuses on recent efforts toward the simultaneous control of LbL film bioactive
      and mechanical properties, with a particular focus on approaches yielding
      cellular outcomes dependent on both of these properties. Challenges and
      opportunities toward the independent control of film rigidity and bioactivity are
      highlighted. 

PMID- 24894806
TI  - Correction of defective CFTR/ENaC function and tightness of cystic fibrosis
      airway epithelium by amniotic mesenchymal stromal (stem) cells.
AB  - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance
      regulator (CFTR) gene, with most of the mortality given by the lung disease.
      Human amniotic mesenchymal stromal (stem) cells (hAMSCs) hold great promise for
      regenerative medicine in the field of lung disease; however, their potential as
      therapeutics for CF lung disease has not been fully explored. In the present
      study, hAMSCs were analysed in co-cultures on Transwell filters with CF
      immortalized airway epithelial cells (CFBE41o- line) at different ratios to
      exploit their potency to resume basic defects associated with CF. The results
      show that F-actin content was increased in co-cultures as compared with CF cells
      and actin was reorganized to form stress fibres. Confocal microscopy studies
      revealed that co-cultures had a tendency of increased expression of occludin and
      ZO-1 at the intercellular borders, paralleled by a decrease in dextran
      permeability, suggestive of more organized tight junctions (TJs).
      Spectrofluorometric analysis of CFTR function demonstrated that hAMSC-CFBE co
      cultures resumed chloride transport, in line with the appearance of the mature
      Band C of CFTR protein by Western blotting. Moreover, hAMSC-CFBE co-cultures, at
      a 1:5 ratio, showed a decrease in fluid absorption, as opposed to CFBE cell
      monolayers that displayed a great rate of fluid resorption from the apical side.
      Our data show that human amniotic MSCs can be used in co-culture with CF
      respiratory epithelial cells to model their engraftment into the airways and have
      the potential to resume a tight epithelium with partial correction of the CF
      phenotype. 

PMID- 24894810
TI  - HLA class II alleles may influence susceptibility to adult dermatomyositis and
      polymyositis in a Han Chinese population.
AB  - BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are idiopathic
      inflammatory myopathies. Genetic variability in human leukocyte antigen (HLA)
      genes plays an important role in the pathogenesis of PM and DM. However, few
      studies on the subject in Chinese populations have been reported thus far.
      METHODS: We studied the influence of HLA polymorphisms on DM and PM
      susceptibility by analyzing HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles in 71 adult
      DM patients, 20 adult PM patients, and 113 controls in a Han Chinese population.
      RESULTS: A positive association was found between HLA-DQA1*0104 and DM (p = 0.01;
      corrected p (pcorr) NS; odds ratio (OR) = 2.58; 95% confidence interval (CI):
      1.18-5.64), while an inverse correlation was noted between HLA-DQB1*0303 and
      myositis patients with interstitial lung inflammation (p = 0.01; pcorr NS; OR =
      0.25; 95% CI: 0.07-0.73). A positive relationship was also observed between HLA
      DRB1*07 and DM (p = 0.01; pcorr NS; OR = 2.26; 95% CI: 1.12-4.59), while HLA
      DRB1*03 seems to be protective against DM (p = 0.01; pcorr NS; OR = 0.26; 95% CI:
      0.06-0.81). The lung complication was closely associated with HLA-DRB1*04 (p =
      0.01; pcorr NS; OR = 2.82; 95% CI: 1.15-6.76) and HLA-DRB1*12 (p = 0.02; pcorr
      NS; OR = 2.52; 95% CI: 1.02-6.07). The frequency of HLA-DRB1*07 was significantly
      higher among myositis patients with dysphagia than among controls (p = 0.01;
      pcorr NS; OR = 4.78; 95% CI: 1.03-24.42). The putative haplotype DRB1*07-DQA1*01
      DQB1*02 was positively correlated with DM (p = 0.03; pcorr NS; OR = 2.90; 95% CI:
      1.02-8.93) and the lung complication (p = 0.02; pcorr NS; OR = 3.45; 95% CI: 1.04
      11.58). CONCLUSIONS: Our results demonstrate that HLA alleles may be involved in
      susceptibility to adult DM and PM in the Han Chinese population.

PMID- 24894811
TI  - Do serrated neoplasms of the small intestine represent a distinct entity?
      Pathological findings and molecular alterations in a series of 13 cases.
AB  - AIMS: To characterize pathological, immunohistochemical and molecular features of
      small intestinal serrated neoplasms. METHODS AND RESULTS: We report 13 serrated
      neoplasms located predominantly in the duodenum (median age, 71 years; male to
      female ratio, 7:6). The serrated adenomas demonstrated prominent serration,
      ectopic crypt formations and cytological features reminiscent of colorectal
      traditional serrated adenomas. Almost half the serrated adenomas demonstrated
      high-grade dysplasia or were associated with an adenocarcinoma.
      Immunohistochemical and molecular analysis showed an intestinal (CDX2-positive)
      phenotype in all tumours, abnormal beta-catenin staining in three cases (23%),
      abnormal p53 expression in four cases (31%), focal loss of MGMT expression in one
      case (8%), KRAS mutation in five cases (38%) and CpG island methylator phenotype
      in six cases (50%). A diffuse pattern of Ki67 expression was present in eight
      adenomas (62%) and was associated with high-grade dysplasia (P = 0.02). No
      BRAF(V600E) mutation or loss of MLH1 expression was observed. CONCLUSIONS: To our
      knowledge, this is the first series reporting serrated adenoma in the small
      intestine, a rare subtype of adenomas resembling traditional serrated adenoma
      with aggressive morphological features. The absence of the BRAF(V600E) mutation
      does not support a role for the serrated neoplasia pathway in the development of
      these lesions, as in colorectal serrated polyps.

PMID- 24894812
TI  - Development and validation of the coronary heart disease scale under the system
      of quality of life instruments for chronic diseases QLICD-CHD: combinations of
      classical test theory and Generalizability Theory.
AB  - BACKGROUND: Quality of life (QOL) for patients with coronary heart disease (CHD)
      is now concerned worldwide with the specific instruments being seldom and no one
      developed by the modular approach. OBJECTIVES: This paper is aimed to develop the
      CHD scale of the system of Quality of Life Instruments for Chronic Diseases
      (QLICD-CHD) by the modular approach and validate it by both classical test theory
      and Generalizability Theory. METHODS: The QLICD-CHD was developed based on
      programmed decision procedures with multiple nominal and focus group discussions,
      in-depth interview, pre-testing and quantitative statistical procedures. 146
      inpatients with CHD were used to provide the data measuring QOL three times
      before and after treatments. The psychometric properties of the scale were
      evaluated with respect to validity, reliability and responsiveness employing
      correlation analysis, factor analyses, multi-trait scaling analysis, t-tests and
      also G studies and D studies of Genralizability Theory analysis. RESULTS: Multi
      trait scaling analysis, correlation and factor analyses confirmed good construct
      validity and criterion-related validity when using SF-36 as a criterion. The
      internal consistency alpha and test-retest reliability coefficients (Pearson r
      and Intra-class correlations ICC) for the overall instrument and all domains were
      higher than 0.70 and 0.80 respectively; The overall and all domains except for
      social domain had statistically significant changes after treatments with
      moderate effect size SRM (standardized response mea) ranging from 0.32 to 0.67. G
      coefficients and index of dependability (F coefficients) confirmed the
      reliability of the scale further with more exact variance components.
      CONCLUSIONS: The QLICD-CHD has good validity, reliability, and moderate
      responsiveness and some highlights, and can be used as the quality of life
      instrument for patients with CHD. However, in order to obtain better reliability,
      the numbers of items for social domain should be increased or the items' quality,
      not quantity, should be improved.

PMID- 24894813
TI  - The construct validity and responsiveness of sensory tests in patients with
      carpal tunnel syndrome.
AB  - BACKGROUND AND PURPOSE: Sensory evaluation is fundamental to evaluation of
      patients with Carpal Tunnel Syndrome (CTS). The purpose of this study was to
      determine the construct validity and responsiveness for sensory threshold tests
      in patients with CTS. METHODS: Sixty-three patients diagnosed with CTS were
      evaluated prior to orthotic intervention and again at follow up at 6 and 12
      weeks. Sensory tests included touch threshold PSSD (Pressure Specified Sensory
      Device) and vibration threshold (Vibrometer). Construct validity was assessed by
      comparing sensory tests to hand function, and dexterity testing using Spearman
      rho (rs). Patients were classified as either responders or non-responders to
      orthotic intervention based on the change score of the Symptom Severity Scale
      (SSS) of 0.5. Responsiveness of the sensory tools was measured using ROC
      (receiver operating characteristic) curves, SRM (Standardized Response Mean), and
      ES (Effect Sizes). RESULTS: The PSSD had low to moderate correlations (rs <=
      0.32) while Vibrometer scores had moderate correlations (rs = 0.36 - 0.41) with
      dexterity scores. The Clinically Important Difference (CID) for the PSSD was
      estimated at 0.15 g/mm(2) but was not discriminative. The Vibrometer demonstrated
      moderate responsiveness, with a SRM = 0.61 and an ES = 0.46 among responders. The
      PSSD had a SRM = 0.09 and an ES = 0.08 and showed low responsiveness for patients
      with a clinically important improvement in symptoms. CONCLUSION: Measurement
      properties suggest that the Vibrometer was preferable to the PSSD because it was
      more correlated to hand function, and was more responsive. Clinicians may choose
      use the Vibrometer opposed to the PSSD for determining important change in
      sensation after orthotic intervention.

PMID- 24894815
TI  - Effects of fasting blood glucose levels and blood pressure and treatment of
      diabetes and hypertension on the incidence of cardiovascular disease: a study of
      740 patients with incident Type 2 diabetes with up to 30 years' follow-up.
AB  - AIMS: To analyse the effects of hyperglycaemia and hypertension and treatment of
      diabetes and hypertension on cardiovascular disease incidence in patients with
      Type 2 diabetes with up to 30 years of follow-up. METHODS: A total of 740
      patients with incident Type 2 diabetes were registered at the Laxa Primary Health
      Care Centre, Sweden between 1972 and 2001. Annual data on mean fasting blood
      glucose, systolic, diastolic and mean arterial blood pressure, and type of
      diabetes and hypertension treatment were obtained from patient records, and
      information on cardiovascular disease, myocardial infarction and stroke events
      was obtained from national registers. RESULTS: During the follow-up period,
      cumulative cardiovascular disease incidence increased significantly with male sex
      (hazard ratio 1.48, 95% CI 1.21-1.82), number of previous cardiovascular disease
      events (hazard ratio 1.13, 95% CI 1.08-1.18), age, per year (HR 1.05, 95% CI 1.04
      1.07), mean fasting blood glucose, per mmol/l (hazard ratio 1.05, 95% CI 1.00
      1.10) BMI (hazard ratio 1.04, 95% CI 1.01-1.06), mean arterial blood pressure,
      per mmHg (hazard ratio 1.02, 95% CI 1.01-1.03), and decreased significantly with
      metformin treatment (hazard ratio 0.58, 95% CI 0.38-0.90) and sulfonylurea
      (hazard ratio 0.73, 95% CI 0.55-0.97). Cumulative myocardial infarction incidence
      increased significantly with male sex, number of previous myocardial infarction
      events, mean fasting blood glucose level, BMI, age and mean arterial blood
      pressure, and decreased with metformin treatment. Cumulative stroke incidence
      increased with number of previous stroke events, age and mean arterial blood
      pressure. CONCLUSIONS: The cumulative incidence of cardiovascular disease and
      myocardial infarction increased with number of previous events and presence of
      hyperglycaemia and hypertension and decreased with pharmacological treatment of
      diabetes. A higher number of previous stroke events increased the cumulative
      incidence of stroke but no protective effect of pharmacological treatment was
      observed.

PMID- 24894814
TI  - Exogenous expression of WT1 gene influences U937 cell biological behaviors and
      activates MAPK and JAK-STAT signaling pathways.
AB  - Wilms' tumor 1 (WT1) gene plays important roles in leukemogenesis. To further
      explore its underlying mechanisms, we transfected two WT1 isoforms, WT1(+17AA/
      KTS) and WT1(+17AA/+KTS) into U937, a WT1-null monoblastic cell line, studied
      their effects on migration, colony formation, apoptosis, gene expression and
      pertinent signaling pathways of U937 cells. The results showed that WT1(+17AA/
      KTS), but not WT1(+17AA/+KTS), enhanced migration and colony forming abilities of
      U937 cells, and suppressed etoposide-induced U937 cell apoptosis. Transfection of
      WT1 isoforms activated gene expressions of chemokine, and induced up-regulation
      of signaling molecules involved in JAK-STAT and MAPK signaling pathways. This
      study showed that exogenous expression of WT1 gene remarkably affected biological
      behaviors of U937 cells, and these effects are possibly mediated by up-regulation
      of genes related to chemokine, JAK-STAT and MAPK signaling pathways. 

PMID- 24894816
TI  - Characterisation of risk factors for stones in hyperuricosuric men attending a
      stone clinic.
AB  - Hyperuricosuria is common among stone formers, but its significance is uncertain.
      To progress our understanding and target treatment, we need to identify and
      characterise patients with uniform underlying pathology. We aimed to identify
      hyperuricosuric patients with a primary defect in renal urate reabsorption (renal
      hyperuricosuria) and to look for associated risk factors for stones. We undertook
      a retrospective cross-sectional database study of 666 male stone formers
      attending the Southampton stone clinic. We estimated filtered urate from plasma
      urate and 24-h creatinine clearance, and the net percentage reabsorbed. 153 men
      had hyperuricosuria (urine urate >4.80 mmol/24 h); 513 had normouricosuria.
      Hyperuricosuric men filtered more urate (median 68.1 and 52.5 mmol/24 h) but the
      ranges overlapped. Thirty hyperuricosuric men with filtered urate below the
      median for normouricosuria were selected as the renal hyperuricosuria group.
      Their normal plasma urate and high urate clearance substantiated this
      classification. In comparison with 60 normouricosuric stone formers matched for
      filtration, they had a higher incidence of hypercalciuria (67 versus 40%), but
      similar, high, frequencies of hyperoxaluria (25 and 11%) and phosphaturia (40 and
      27%).There were no differences in age at first stone, incidence of stone
      recurrence or positive family history (20 and 25%). The findings demonstrate
      multiple risk factors for stones in this subgroup. In comparison, the 30
      hyperuricosuric men with the highest filtration had a higher incidence of
      hyperoxaluria (58%) but fewer (7%) had a positive family history. Creatinine
      clearance was raised in 73%. An excessive protein intake might be a major
      correctable factor underlying these abnormalities.

PMID- 24894819
TI  - Size-dependent water structures in carbon nanotubes.
AB  - Water surrounded by hydrophobic interfaces affects a variety of chemical
      reactions and biological activities. Carbon nanotubes (CNTs) can be used to
      investigate the behavior of water at hydrophobic interfaces. Here, we determined
      the fundamental unit of water by evaluating the ice-like cluster formation of
      water in the limited hydrophobic nanospaces of CNTs, using X-ray diffraction and
      molecular simulation analysis. The water in CNTs with a diameter of 1 nm had
      fewer hydrogen bonds than bulk water under ambient conditions. In CNTs with
      diameters of 2 and 3 nm, water formed nanoclusters even under ambient conditions,
      because of prolific hydrogen bonding; predominant ice-like cluster formation was
      induced in the 2-3 nm nanospaces. The results confirming the cluster formation in
      the CNTs also demonstrated that the critical cluster size was 0.8-3.4 nm. The
      fundamental cluster size was 0.8 nm; these results indicated that 0.8 nm clusters
      are the fundamental units of water assemblies.

PMID- 24894817
TI  - Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic
      anti-tumor immunity.
AB  - Direct in vivo administration of messenger RNA (mRNA) delivered in both naked and
      nanoparticle formats are actively investigated because the use of dendritic cells
      transfected ex vivo with mRNA for cancer therapy is expensive and needs
      significant infrastructure. Notably, intravenous and subcutaneous injections are
      the only routes of administration tested for mRNA nanoparticle tumor vaccination.
      In this report, we demonstrate that tumor immunity can be achieved via nasal
      administration of mRNA. Mice nasally immunized with mRNA delivered in
      nanoparticle format demonstrate delayed tumor progression in both prophylactic
      and therapeutic immunization models. The observed tumor immunity correlates with
      splenic antigen-specific CD8+ T cells and is achieved only when mRNA is delivered
      in nanoparticle but not in naked format. In conclusion, we demonstrate, as a
      proof-of-concept, a non-invasive approach to mRNA tumor vaccination, increasing
      its potential as a broadly applicable and off-the-shelf therapy for cancer
      treatment. 

PMID- 24894818
TI  - Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN
      contribute to breast cancer susceptibility: results from a Breast Cancer Family
      Registry case-control mutation-screening study.
AB  - INTRODUCTION: The MRE11A-RAD50-Nibrin (MRN) complex plays several critical roles
      related to repair of DNA double-strand breaks. Inherited mutations in the three
      components predispose to genetic instability disorders and the MRN genes have
      been implicated in breast cancer susceptibility, but the underlying data are not
      entirely convincing. Here, we address two related questions: (1) are some rare
      MRN variants intermediate-risk breast cancer susceptibility alleles, and if so
      (2) do the MRN genes follow a BRCA1/BRCA2 pattern wherein most susceptibility
      alleles are protein-truncating variants, or do they follow an ATM/CHEK2 pattern
      wherein half or more of the susceptibility alleles are missense substitutions?
      METHODS: Using high-resolution melt curve analysis followed by Sanger sequencing,
      we mutation screened the coding exons and proximal splice junction regions of the
      MRN genes in 1,313 early-onset breast cancer cases and 1,123 population controls.
      Rare variants in the three genes were pooled using bioinformatics methods similar
      to those previously applied to ATM, BRCA1, BRCA2, and CHEK2, and then assessed by
      logistic regression. RESULTS: Re-analysis of our ATM, BRCA1, and BRCA2 mutation
      screening data revealed that these genes do not harbor pathogenic alleles (other
      than modest-risk SNPs) with minor allele frequencies>0.1% in Caucasian Americans,
      African Americans, or East Asians. Limiting our MRN analyses to variants with
      allele frequencies of <0.1% and combining protein-truncating variants, likely
      spliceogenic variants, and key functional domain rare missense substitutions, we
      found significant evidence that the MRN genes are indeed intermediate-risk breast
      cancer susceptibility genes (odds ratio (OR)=2.88, P=0.0090). Key domain missense
      substitutions were more frequent than the truncating variants (24 versus 12
      observations) and conferred a slightly higher OR (3.07 versus 2.61) with a lower
      P value (0.029 versus 0.14). CONCLUSIONS: These data establish that MRE11A,
      RAD50, and NBN are intermediate-risk breast cancer susceptibility genes. Like ATM
      and CHEK2, their spectrum of pathogenic variants includes a relatively high
      proportion of missense substitutions. However, the data neither establish whether
      variants in each of the three genes are best evaluated under the same analysis
      model nor achieve clinically actionable classification of individual variants
      observed in this study.

PMID- 24894820
TI  - Role of SIRT1 in Streptococcus pneumoniae-induced human beta-defensin-2 and
      interleukin-8 expression in A549 cell.
AB  - Streptococcus pneumoniae is an important pathogen of pneumonia in human. Human
      alveolar epithelium acts as an effective barrier and is an active participant in
      host defense against invasion of bacterial by production of various mediators.
      Sirtuin 1 (SIRT1), the prototypic class III histone deacetylase, is involved in
      the molecular control of lifespans and immune responses. This study aimed at
      examining the role of SIRT1 in mediating S. pneumoniae-induced human beta
      defensin-2 (hBD2) and interleukin-8(IL-8) expression in the alveolar epithelial
      cell line A549 and the underlying mechanisms involved. A549 cells were infected
      with S. pneumoniae for indicated times. Exposure of A549 cells to S. pneumoniae
      increased the expressions of SIRT1 protein, hBD2 and IL-8 mRNA, and protein. The
      SIRT1 activator resveratrol enhanced S. pneumoniae-induced gene expression of
      hBD2 but decreased IL-8 mRNA levels. Blockade of SIRT1 activity by the SIRT1
      inhibitors nicotinamide reduced S. pneumoniae-induced hBD2 mRNA expression but
      increased its stimulatory effects on IL-8 mRNA. S. pneumoniae-induced activation
      of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
      kinase (MAPK). SIRT1 expression was attenuated by selective inhibitors of ERK and
      p38 MAPK. The hBD2 mRNA production was decreased by pretreatment with p38 MAPK
      inhibitor but not with ERK inhibitor, whereas the IL-8 mRNA expression was
      controlled by phosphorylation of ERK. These results suggest that SIRT1 mediates
      the induction of hBD2 and IL-8 gene expression levels in A549 cell by S.
      pneumoniae. SIRT1 may play a key role in host immune and defense response in
      A549. 

PMID- 24894821
TI  - Berberine diminishes side population and down-regulates stem cell-associated
      genes in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2.
AB  - Cancer stem cells play an important role in metastasis and the relapse of drug
      resistant cancers. Side-population (SP) cells are capable of effluxing Hoechst
      33342 dye and are referred to as cancer stem cells. We investigated the effect of
      berberine on pancreatic cancer stem cells of PANC-1 and MIA PaCa-2. For both cell
      lines, the proportions of SP cells in the presence of berberine were investigated
      and compared to the proportions in the presence of gemcitabine, a standard
      pancreatic anti-cancer drug. The proportions of SP cells in the PANC-1 and MIA
      PaCa-2 cell lines were about 9 and <0.1%, respectively. After berberine and
      gemcitabine treatments, the SP cell proportion of PANC-1 decreased to 5.7 +/- 2.0
      and 6.8 +/- 0.8%, respectively, which compares to the control proportion of (9.7
      +/- 1.7). After berberine and gemcitabine treatment of PANC-1, of the four stem
      cell-associated genes (SOX2, POU5F1, NANOG, and NOTCH1), all but NOTCH1 were down
      regulated. Unfortunately, the effect of berberine and gemcitabine treatments on
      MIA PaCa-2 SP cells could not be clearly observed because SP cells represented
      only a very small proportion of MIA PaCa-2 cells. However, SOX2, POU5F1, and
      NANOG genes were shown to be effectively down-regulated in the MIA PaCa-2 cell
      line as a whole. Taken together, these results indicate that berberine is as
      effective at targeting pancreatic cancer cell lines as gemcitabine. Therefore, we
      believe that POU5F1, SOX2, and NANOG can serve as potential markers, and
      berberine may be an effective anti-cancer agent when targeting human pancreatic
      cancer cells and/or their cancer stem cells.

PMID- 24894822
TI  - CD73-TNAP crosstalk regulates the hypertrophic response and cardiomyocyte
      calcification due to alpha1 adrenoceptor activation.
AB  - Cluster of differentiation 73 (CD73) is an ecto-5' nucleotidase which catalyzes
      the conversion of AMP to adenosine. One of the many functions of adenosine is to
      suppress the activity of tissue nonspecific alkaline phosphatase (TNAP), an
      enzyme important in regulating intracellular calcification. Since myocardial
      calcification is associated with various cardiac disease states, we studied the
      individual roles and crosstalk between CD73 and TNAP in regulating myocyte
      responses to the alpha1 adrenoceptor agonist phenylephrine in terms of
      calcification and hypertrophy. Cultured neonatal rat cardiomyocytes were treated
      with 10 uM phenylephrine for 24 h in the absence or presence of the stable
      adenosine analog 2-chloro-adenosine, the TNAP inhibitor tetramisole or the CD73
      inhibitor alpha,beta-methylene ADP. Phenylephrine produced marked hypertrophy as
      evidenced by significant increases in myocyte surface area and ANP gene
      expression, as well as calcification determined by Alizarin Red S staining. These
      responses were associated with reduced CD73 gene and protein expression and CD73
      activity. Conversely, TNAP expression and activity were significantly increased
      although both were suppressed by 2-chloro-adenosine. CD73 inhibition alone
      significantly reduced myocyte-derived adenosine levels by >50 %, and directly
      induced hypertrophy and calcification in the absence of phenylephrine. These
      responses and those to phenylephrine were abrogated by TNAP inhibition. We
      conclude that TNAP contributes to the hypertrophic effect of phenylephrine, as
      well as its ability to produce cardiomyocyte calcification. These responses are
      minimized by CD73-dependent endogenously produced adenosine.

PMID- 24894824
TI  - The impact of exposure-biased sampling designs on detection of gene-environment
      interactions in case-control studies with potential exposure misclassification.
AB  - With limited funding and biological specimen availability, choosing an optimal
      sampling design to maximize power for detecting gene-by-environment (G-E)
      interactions is critical. Exposure-enriched sampling is often used to select
      subjects with rare exposures for genotyping to enhance power for tests of G-E
      effects. However, exposure misclassification (MC) combined with biased sampling
      can affect characteristics of tests for G-E interaction and joint tests for
      marginal association and G-E interaction. Here, we characterize the impact of
      exposure-biased sampling under conditions of perfect exposure information and
      exposure MC on properties of several methods for conducting inference. We assess
      the Type I error, power, bias, and mean squared error properties of case-only,
      case-control, and empirical Bayes methods for testing/estimating G-E interaction
      and a joint test for marginal G (or E) effect and G-E interaction across three
      biased sampling schemes. Properties are evaluated via empirical simulation
      studies. With perfect exposure information, exposure-enriched sampling schemes
      enhance power as compared to random selection of subjects irrespective of
      exposure prevalence but yield bias in estimation of the G-E interaction and
      marginal E parameters. Exposure MC modifies the relative performance of sampling
      designs when compared to the case of perfect exposure information. Those
      conducting G-E interaction studies should be aware of exposure MC properties and
      the prevalence of exposure when choosing an ideal sampling scheme and method for
      characterizing G-E interactions and joint effects. 

PMID- 24894825
TI  - Summary of relationships between exchangeability, biasing paths and bias.
AB  - Definitions and conceptualizations of confounding and selection bias have evolved
      over the past several decades. An important advance occurred with development of
      the concept of exchangeability. For example, if exchangeability holds, risks of
      disease in an unexposed group can be compared with risks in an exposed group to
      estimate causal effects. Another advance occurred with the use of causal graphs
      to summarize causal relationships and facilitate identification of causal
      patterns that likely indicate bias, including confounding and selection bias.
      While closely related, exchangeability is defined in the counterfactual-model
      framework and confounding paths in the causal-graph framework. Moreover, the
      precise relationships between these concepts have not been fully described. Here,
      we summarize definitions and current views of these concepts. We show how bias,
      exchangeability and biasing paths interrelate and provide justification for key
      results. For example, we show that absence of a biasing path implies
      exchangeability but that the reverse implication need not hold without an
      additional assumption, such as faithfulness. The close links shown are expected.
      However confounding, selection bias and exchangeability are basic concepts, so
      comprehensive summarization and definitive demonstration of links between them is
      important. Thus, this work facilitates and adds to our understanding of these
      important biases. 

PMID- 24894823
TI  - Risperidone and the 5-HT2A receptor antagonist M100907 improve probabilistic
      reversal learning in BTBR T + tf/J mice.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by
      impaired social interactions with restricted interests and repetitive behaviors
      (RRBs). RRBs can severely limit daily living and be particularly stressful to
      family members. To date, there are limited options for treating this feature in
      ASD. Risperidone, an atypical antipsychotic, is approved to treat irritability in
      ASD, but less is known about whether it is effective in treating "higher order"
      RRBs, for example cognitive inflexibility. Risperidone also has multiple receptor
      targets in which only a subset may be procognitive and others induce cognitive
      impairment. 5HT2A receptor blockade represents one promising and more targeted
      approach, as various preclinical studies have shown that 5HT2A receptor
      antagonists improve cognition. The present study investigated whether risperidone
      and/or M100907, a 5HT2A receptor antagonist, improved probabilistic reversal
      learning performance in the BTBR T + tf/J (BTBR) mouse model of autism. The
      effects of these treatments were also investigated in C57BL/6J (B6) mice as a
      comparison strain. Using a spatial reversal learning test with 80/20
      probabilistic feedback, similar to one in which ASD individuals exhibit
      impairments, both risperidone (0.125 mg) and M100907 (0.01 and 0.1 mg) improved
      reversal learning in BTBR mice. Risperidone (0.125 mg) impaired reversal learning
      in B6 mice. Improvement in probabilistic reversal learning performance resulted
      from treatments enhancing the maintenance of the newly correct choice pattern.
      Because risperidone can lead to unwanted side effects, treatment with a specific
      5HT2A receptor antagonist may improve cognitive flexibility in individuals with
      ASD while also minimizing unwanted side effects.

PMID- 24894826
TI  - Dairy foods intake and risk of Parkinson's disease: a dose-response meta-analysis
      of prospective cohort studies.
AB  - Dairy foods have been linked to Parkinson's disease (PD), and a meta-analysis of
      prospective cohort studies on dairy foods intake and PD risk was conducted.
      Eligible studies were identified in a literature search of EMBASE and PubMed up
      to April 2014. Seven results from prospective studies were included, including
      1,083 PD cases among 304,193 subjects. The combined risk of PD for highest vs.
      lowest level of dairy foods intake was 1.40 (1.20-1.63) overall, 1.66 (1.29-2.14)
      for men and 1.15 (0.85-1.56) for women. For highest vs. lowest level, the PD risk
      was 1.45 (1.23-1.73) for milk, 1.26 (0.99-1.60) for cheese, 0.95 (0.76-1.20) for
      yogurt and 0.76 (0.51-1.13) for butter. The linear dose-response relationship
      showed that PD risk increased by 17% [1.17 (1.06-1.30)] for every 200 g/day
      increment in milk intake (Pfor non-linearity = 0.22), and 13% [1.13 (0.91-1.40)]
      for every 10 g/day increment in cheese intake (Pfor non-linearity = 0.39). The
      absolute risk differences were estimated to be 2-4 PD cases per 100,000 person
      years for every 200 g/day increment in milk intake, and 1-3 PD cases per 100,000
      person-years for every 10 g/day increment in cheese intake. Dairy foods (milk,
      cheese) might be positively associated with increased risk of PD, especially for
      men.

PMID- 24894828
TI  - Evaluating the extent of LINE-1 mobility following exposure to heavy metals in
      HepG2 cells.
AB  - The long interspersed elements-1 (LINE1 or L1 retrotransposon) constitute 17% of
      the human genome and retain mobility properties within the genome. At present, 80
      100 human L1 elements are thought to be active in the genome. The mobilization of
      these active elements may be influenced upon exposure to the heavy metals. In the
      present study, we evaluated the association of aluminum, lead, and copper
      exposure with L1 retrotransposition in human hepatocellular carcinoma (HepG2)
      cell line. An in vitro retrotransposition assay using an enhanced green
      fluorescent protein (EGFP)-tagged L1RP cassette was established to track EGFP
      shining as the mark of retrotransposition. Following determination of
      noncytotoxic concentrations of these metals, pL1RP-EGFP-transfected HepG2 cells
      were subjected to long-term treatment. Flow cytometry analysis of cells treated
      with various concentrations of these metals along with quantitative real-time PCR
      was used to quantify L1 retrotransposition frequencies. Aluminum significantly
      increased L1 retrotransposition frequency, while no significant association was
      found concerning lead exposure and L1 retrotransposition. Copper treatment
      downregulated L1 retrotransposition as a result of EGFP-tagged L1RP expression.
      Our findings suggest that aluminum might have the potential to cause genomic
      instability by the enhancement of L1 mobilization. Thus, the risk of induced L1
      retrotransposition should be considered during drug safety evaluation and risk
      assessments of exposure to toxic environmental agents. Further studies are needed
      for a more robust assay to evaluate any associations between long-term lead
      exposure and L1 mobility in cell culture assay.

PMID- 24894830
TI  - Protective role of selenium on pepper exposed to cadmium stress during
      reproductive stage.
AB  - The aim of the present study was to examine the effects of exogenous selenium
      (Se) supplementation on the tolerance of pepper (Capsicum annuum L.) cv.
      Suryamukhi Cluster plants to cadmium (Cd) phytotoxicity at the reproductive
      stage. The pepper plants were supplied with Cd (0, 0.25 or 0.50 mM) and Se (0, 3
      or 7 MUM), individually or simultaneously, three times during the experiment. The
      obtained results show that Cd had deleterious effect on pepper plants at the
      reproductive stage. However, Se supplementation improved the flower number, fruit
      number and fruit diameter in plants exposed to 0.50 mM Cd. Moreover, both Se
      concentrations used in 0.25 mM Cd-treated plants and 3 MUM Se in 0.50 mM Cd
      treated plants enhanced fruit yield per plant as compared to Cd-alone treatment.
      The chlorophyll concentrations significantly increased in the fruits of Cd
      exposed plants after Se addition. However, Se supplementation reduced total
      carotenoids and total soluble solid (TSS) concentrations in the pepper fruits
      exposed to Cd. Selenium also generally enhanced the total antioxidant activity of
      pepper fruits subjected to Cd. Both Se concentrations used increased mean
      productivity (MP), stress tolerance index (STI) and yield stability index (YSI)
      in plants grown in the medium containing 0.25 mM Cd. At low concentration (3
      MUM), Se significantly increased geometric mean productivity (GMP), STI and YSI
      of plant exposed to 0.50 mM Cd. The highest Cd concentration in the fruits was
      achieved at 0.50 mM Cd and Se application significantly reduced Cd accumulation
      in the Cd-exposed plants. Our results indicate that application of Se can
      alleviate Cd toxicity in pepper plants at the reproductive stage by restricting
      Cd accumulation in fruits, enhancing their antioxidant activity and thus
      improving the reproductive and stress tolerance parameters.

PMID- 24894829
TI  - Effect of selenium on selenoprotein expression in the adipose tissue of chickens.
AB  - This study describes the effects of selenium (Se) deficiency on the messenger
      ribonucleic acid (mRNA) expression of 25 selenoproteins (Sels) (including
      glutathione peroxidases (GPx1-GPx4), thioredoxin reductases (TrxR1-TrxR3),
      iodothyronine deiodinases (ID1-ID3), selenophosphate synthetase 2 (SPS2), 15-kDa
      Sel (Sel15), SelH, SelI, SelK, SelM, Sepn1, SelO, Sepx, Selpb, SelS, SelT, SelW,
      Sepp1, and SelU in the adipose tissues (subcutaneous adipose, visceral adipose,
      and articular adipose) of chickens. One hundred and fifty 1-day-old chickens were
      randomly assigned to two groups of 75 each and were fed a low-Se diet (0.032
      mg/kg Se) or a control diet (0.282 mg/kg Se). The expression levels of 25 Sel
      mRNAs were determined on days 35, 45, and 55 from three parts (subcutaneous
      adipose, visceral adipose, and articular adipose) of the chicken adipose tissues.
      The results showed that the expression levels of the 25 Sel mRNAs were
      significantly lower (P < 0.05) in the low-selenium group than in the control
      group. In addition, the Sel mRNA expression levels in the three adipose tissues
      were observed to decrease in a time-dependent manner with increasing feeding
      time.

PMID- 24894831
TI  - Effects of static magnetic field exposure on plasma element levels in rat.
AB  - The interaction of static magnetic fields (SMFs) with living organisms is a
      rapidly growing field of investigation. The magnetic fields (MFs) effect observed
      with radical pair recombination is one of the well-known mechanisms by which MFs
      interact with biological systems. SMF influenced cellular antioxidant defense
      mechanisms by affecting antioxidant enzymes such as superoxide dismutase (SOD),
      glutathione peroxidase (GPx), and catalase (CAT). However, there were
      insufficient reports about the effects of SMF on macro and trace elements in
      serum, and the results were contradictory until now. In the current study, 12
      rats were divided into two groups, namely as control and exposure group (128 mT
      and 1 h/day during five consecutive days). The macro and trace element
      concentrations in serum were examined. No significant difference was observed in
      the sodium (Na), potassium (K), calcium (Ca), phosphorus (P), and selenium (Se)
      levels in rat compared to control. By contrast, exposure to SMF showed an
      increase in the zinc (Zn) level and a decrease in iron (Fe) concentration. Under
      our experimental conditions, SMF exposure cannot affect the plasma levels of
      macroelements, while it can disrupt Zn and Fe concentrations in rat.

PMID- 24894833
TI  - Production of lactic acid using a new homofermentative Enterococcus faecalis
      isolate.
AB  - Lactic acid is an intermediate-volume specialty chemical for a wide range of food
      and industrial applications such as pharmaceuticals, cosmetics and chemical
      syntheses. Although lactic acid production has been well documented, improved
      production parameters that lead to reduced production costs are always of
      interest in industrial developments. In this study, we describe the production of
      lactic acid at high concentration, yield and volumetric productivity utilizing a
      novel homofermentative, facultative anaerobe Enterococcus faecalis CBRD01. The
      highest concentration of 182 g lactic acid l(-1) was achieved after 38 h of fed
      batch fermentation on glucose. The bacterial isolate utilized only 2-13% of
      carbon for its growth and energy metabolism, while 87-98% of carbon was converted
      to lactic acid at an overall volumetric productivity of 5 g l(-1)  h(-1). At 13 h
      of fermentation, the volumetric productivity of lactate production reached 10.3 g
      l(-1)  h(-1), which is the highest ever reported for microbial production of
      lactic acid. The lactic acid produced was of high purity as formation of other
      metabolites was less than 0.1%. The present investigation demonstrates a new
      opportunity for enhanced production of lactic acid with potential for reduced
      purification costs.

PMID- 24894832
TI  - Analysis of differentially expressed genes in two immunologically distinct
      strains of Eimeria maxima using suppression subtractive hybridization and dot
      blot hybridization.
AB  - BACKGROUND: It is well known that different Eimeria maxima strains exhibit
      significant antigenic variation. However, the genetic basis of these phenotypes
      remains unclear. METHODS: Total RNA and mRNA were isolated from unsporulated
      oocysts of E. maxima strains SH and NT, which were found to have significant
      differences in immunogenicity in our previous research. Two subtractive cDNA
      libraries were constructed using suppression subtractive hybridization (SSH) and
      specific genes were further analyzed by dot-blot hybridization and qRT-PCR
      analysis. RESULTS: A total of 561 clones were selected from both cDNA libraries
      and the length of the inserted fragments was 0.25-1.0 kb. Dot-blot hybridization
      revealed a total of 86 differentially expressed clones (63 from strain SH and 23
      from strain NT). Nucleotide sequencing analysis of these clones revealed ten
      specific contigs (six from strain SH and four from strain NT). Further analysis
      found that six contigs from strain SH and three from strain NT shared significant
      identities with previously reported proteins, and one contig was presumed to be
      novel. The specific differentially expressed genes were finally verified by RT
      PCR and qRT-PCR analyses. CONCLUSIONS: The data presented here suggest that
      specific genes identified between the two strains may be important molecules in
      the immunogenicity of E. maxima that may present potential new drug targets or
      vaccine candidates for coccidiosis.

PMID- 24894834
TI  - Identification of primary and secondary metabolites with phosphorus status
      dependent abundance in Arabidopsis, and of the transcription factor PHR1 as a
      major regulator of metabolic changes during phosphorus limitation.
AB  - Massive changes in gene expression occur when plants are subjected to phosphorus
      (P) limitation, but the breadth of metabolic changes in these conditions and
      their regulation is barely investigated. Nearly 350 primary and secondary
      metabolites were profiled in shoots and roots of P-replete and P-deprived
      Arabidopsis thaliana wild type and mutants of the central P-signalling components
      PHR1 and PHO2, and microRNA399 overexpresser. In the wild type, the levels of 87
      primary metabolites, including phosphorylated metabolites but not 3
      phosphoglycerate, decreased, whereas the concentrations of most organic acids,
      amino acids, nitrogenous compounds, polyhydroxy acids and sugars increased.
      Furthermore, the levels of 35 secondary metabolites, including glucosinolates,
      benzoides, phenylpropanoids and flavonoids, were altered during P limitation.
      Observed changes indicated P-saving strategies, increased photorespiration and
      crosstalk between P limitation and sulphur and nitrogen metabolism. The phr1
      mutation had a remarkably pronounced effect on the metabolic P-limitation
      response, providing evidence that PHR1 is a key factor for metabolic
      reprogramming during P limitation. The effects of pho2 or microRNA399
      overexpression were comparatively minor. In addition, positive correlations
      between metabolites and gene transcripts encoding pathway enzymes were revealed.
      This study provides an unprecedented metabolic phenotype during P limitation in
      Arabidopsis. 

PMID- 24894835
TI  - Isolation, culture, and transfection of melanocytes.
AB  - Located in the basal epidermis and hair follicles, melanocytes of the integument
      are responsible for its coloration through production of melanin pigments.
      Melanin is produced in lysosomal-like organelles called melanosomes. In humans,
      this skin pigmentation acts as an ultraviolet radiation filter. Abnormalities in
      the division of melanocytes are quite common, with potentially oncogenic growth
      usually followed by cell senescence producing benign naevi (moles), or
      occasionally melanoma. Therefore, melanocytes are a useful model for studying
      melanoma, as well as pigmentation and organelle transport and the diseases
      affecting these mechanisms. This chapter focuses on the isolation, culture, and
      transfection of human and murine melanocytes. The first basic protocol describes
      the primary culture of melanocytes from human skin and the maintenance of growing
      cultures. The second basic protocol details the subculture and preparation of
      mouse keratinocyte feeder cells. The primary culture of melanocytes from mouse
      skin is described in the third basic protocol, and, lastly, the fourth basic
      protocol outlines a technique for transfecting melanocytes and melanoma cells.

PMID- 24894836
TI  - Direct measurement of intracellular pressure.
AB  - A method to directly measure the intracellular pressure of adherent, migrating
      cells is described in this unit. This approach is based on the servo-null method
      where a microelectrode is introduced into the cell to directly measure the
      physical pressure of the cytoplasm. We also describe the initial calibration of
      the microelectrode, as well as the application of the method to cells migrating
      inside three-dimensional (3-D) extracellular matrix (ECM).

PMID- 24894837
TI  - Isolation, culture, and transient transformation of plant protoplasts.
AB  - Transient gene expression in protoplasts, which has been used in several plant
      species, is an important and versatile tool for rapid functional gene analysis,
      protein subcellular localization, and biochemical manipulations. This unit
      describes transient gene expression by electroporation of DNA into protoplasts of
      Arabidopsis or tobacco suspension-cultured cells and by polyethylene glycol (PEG)
      mediated DNA transformation into protoplasts derived from rice leaf sheaths. PEG
      mediated DNA transformation for transient gene expression in rice protoplasts in
      suspension culture is also described as an alternative technique. Methods for
      collecting intracellular and secreted proteins are also provided.

PMID- 24894839
TI  - Analysis of survival factors in patients with intermediate-advanced
      hepatocellular carcinoma treated with transcatheter arterial chemoembolization
      combined with sorafenib.
AB  - PURPOSE: To retrospectively analyze the efficacy and safety of transcatheter
      arterial chemoembolization (TACE) in combination with sorafenib for the treatment
      of patients with intermediate-advanced hepatocellular carcinoma (HCC) and assess
      the prognostic impact of baseline characteristics. METHODS: Patients with
      intermediate-advanced HCC received TACE combined with sorafenib in this Phase 2
      clinical trial. The primary outcome was median time to disease progression
      (mTTP). Secondary outcomes were median overall survival (mOS), the disease
      benefit rate and the sorafenib-related adverse events (AEs). Baseline
      characteristics' impacts on prognosis were analyzed by univariate COX
      proportional hazards regression model. RESULTS: From June 2008 to June 2013, 75
      patients were enrolled. At the end of the study, 54 patients were dead or lost to
      follow-up and 21 patients survived. This combination therapy resulted in a mTTP
      of 7.09 months (95 % CI, 1.5-45 months) and a mOS of 11.44 months (95 % CI, 1.5
      45 months). The disease benefit rate was 88 %. Child-Pugh score (P = 0.000),
      Eastern Cooperative Oncology Group performance status (P = 0.001), Barcelona
      Clinic Liver Cancer stage (P = 0.000), sorafenib treatment regimen (P = 0.001),
      presence of extrahepatic metastasis (P = 0.002), and type of tumor (P = 0.027)
      were significantly correlated with OS. Multivariate analysis revealed Child-Pugh
      score (P = 0.001) and BCLC stage (P = 0.002) as significant independent
      prognostic predictors for OS. AEs were HFSR (18.7 %), gastrointestinal reactions
      (13.3 %), liver dysfunction (6.7 %), myelosuppression (5.3 %), fatigue (4 %), and
      hypertension (1.3 %). CONCLUSIONS: TACE in combination with sorafenib might have
      acceptable safety and efficiency in the treatment of intermediate-advanced HCC.

PMID- 24894838
TI  - Running away from side effects: physical exercise as a complementary intervention
      for breast cancer patients.
AB  - The number of breast cancer survivors increases every year, thanks to the
      development of new treatments and screening techniques. However, patients present
      with numerous side effects that may affect their quality of life. Exercise has
      been demonstrated to reduce some of these side effects, but in spite of this, few
      breast cancer patients know and follow the exercise recommendations needed to
      remain healthy. In this review, we describe the different breast cancer
      treatments and the related side effects and implications of exercise in relation
      to these. We propose that exercise could be an integrative complementary
      intervention to improve physiological, physical and psychological factors that
      affect survival and quality of life of these patients. For that reason, the main
      objective of this review is to provide a general overview of exercise benefits in
      breast cancer patients and recommendations of how to design exercise
      interventions in patients with different side effects. 

PMID- 24894840
TI  - Whole brain radiation therapy followed by intensity-modulated boosting treatment
      combined with concomitant temozolomide for brain metastases from non-small-cell
      lung cancer.
AB  - BACKGROUND: Brain metastases (BMs) represent an important cause of morbidity in
      patients with non-small-cell lung cancer (NSCLC) and are associated with a mean
      survival of <1 year. Thus, new regimens improving the outcome of these patients
      are urgently needed. We have evaluated the response to treatment, overall
      survival, disease progression, and adverse effects of a concomitant treatment
      with whole brain radiation therapy (WBRT) followed by intensity-modulated
      boosting RT (IMBRT) and temozolomide (TMZ) in patients with BMs from NSCLC.
      METHODS: A total of 32 patients with no more than four BMs were enrolled in this
      retrospective study. Patients received 30 Gy of WBRT in 15 fractions and followed
      by 20 Gy of IMBRT in 10 fractions with concomitant TMZ of 75 mg/m(2)/day orally
      during RT and continued TMZ therapy (150-200 mg/m(2)/day for 5 days every 28 days
      for an additional 2-6 cycles after RT). RESULTS: Three patients had a complete
      response, 9 patients had a partial response, while 15 patients had stable
      disease; therefore, the objective responses achieved 37.5 %. Median overall
      survival was 8.0 months and median time to progression was 5.5 months. Common
      treatment-related adverse effects (Grade <=2) included nausea, vomiting, and
      asthenia. Grade 3 or worse hematologic toxicities were rare. No patient presented
      with gross neurocognitive dysfunction. CONCLUSION: WBRT followed by IMBRT
      combined with concomitant TMZ is well tolerated, yielding an encouraging
      objective response rate; however, overall survival improves slightly comparing
      with RTOG 9508 randomized trial.

PMID- 24894841
TI  - A prospective study of serum metabolites and colorectal cancer risk.
AB  - BACKGROUND: Colorectal cancer is highly prevalent, and the vast majority of cases
      are thought to be sporadic, although few risk factors have been identified. Using
      metabolomics technology, our aim was to identify biomarkers prospectively
      associated with colorectal cancer. METHODS: This study included 254 incident
      colorectal cancers and 254 matched controls nested in the Prostate, Lung,
      Colorectal, and Ovarian Cancer Screening Trial. Serum samples were collected at
      baseline, and the mean length of follow-up was 8 years. Serum metabolites were
      analyzed by ultra-high performance liquid-phase chromatography with tandem mass
      spectrometry, and gas chromatography coupled with mass spectrometry. Conditional
      logistic regression was used to calculate odds ratios (OR) and 95% confidence
      intervals (CI) for metabolites above the limit of detection and present in at
      least 80% of participants. RESULTS: A total of 676 serum metabolites were
      measured; of these, 447 were of known identity and 278 of these were present in
      >80% of individuals. Overall, there was no association between serum metabolites
      and colorectal cancer; however, some suggestive associations were observed
      between individual metabolites and colorectal cancer but none reached statistical
      significance after Bonferroni correction for multiple comparisons. For example,
      leucyl-leucine was inversely associated (OR comparing the 90th to the 10th
      percentile = 0.50; 95% CI = 0.32-0.80; P = .003). In sex-stratified analyses,
      serum glycochenodeoxycholate was positively associated with colorectal cancer
      among women (OR(90th vs.10th percentile)  = 5.34; 95% CI = 2.09-13.68; P =
      .0001). CONCLUSIONS: No overall associations were observed between serum
      metabolites and colorectal cancer, but serum glycochenodeoxycholate, a bile acid
      metabolite, was positively associated with colorectal cancer among women.

PMID- 24894842
TI  - Improved MALDI-TOF microbial mass spectrometry imaging by application of a
      dispersed solid matrix.
AB  - The key step in high quality microbial matrix-assisted laser
      desorption/ionization mass spectrometry imaging (microbial MALDI MSI) is the
      fabrication of a homogeneous matrix coating showing a fine-grained morphology.
      This application note addresses a novel method to apply solid MALDI matrices onto
      microbial cultures grown on thin agar media. A suspension of a mixture of 2,5-DHB
      and alpha-CHCA is sprayed onto the agar sample surface to form highly homogeneous
      matrix coatings. As a result, the signal intensities of metabolites secreted by
      the fungus Aspergillus fumigatus were found to be clearly enhanced. 

PMID- 24894843
TI  - Comparison of three plasma sources for ambient desorption/ionization mass
      spectrometry.
AB  - Plasma-based desorption/ionization sources are an important ionization technique
      for ambient surface analysis mass spectrometry. In this paper, we compare and
      contrast three competing plasma based desorption/ionization sources: a radio
      frequency (rf) plasma needle, a dielectric barrier plasma jet, and a low
      temperature plasma probe. The ambient composition of the three sources and their
      effectiveness at analyzing a range of pharmaceuticals and polymers were assessed.
      Results show that the background mass spectrum of each source was dominated by
      air species, with the rf needle producing a richer ion spectrum consisting mainly
      of ionized water clusters. It was also seen that each source produced different
      ion fragments of the analytes under investigation: this is thought to be due to
      different substrate heating, different ion transport mechanisms, and different
      electric field orientations. The rf needle was found to fragment the analytes
      least and as a result it was able to detect larger polymer ions than the other
      sources. 

PMID- 24894844
TI  - New insight into the contrast in diffusional kurtosis images: does it depend on
      magnetic susceptibility?
AB  - PURPOSE: In this MRI study, diffusional kurtosis imaging (DKI) and T2 * multiecho
      relaxometry were measured from the white matter (WM) of human brains and
      correlated with each other, with the aim of investigating the influence of
      magnetic-susceptibility (Deltachi (H2O-TISSUE) ) on the contrast. METHODS: We
      focused our in vivo analysis on assessing the dependence of mean, axial, and
      radial kurtosis (MK, K|| , K? ), as well as DTI indices on Deltachi (H2O-TISSUE)
      (quantified by T2 *) between extracellular water and WM tissue molecules.
      Moreover, Monte Carlo (MC) simulations were used to elucidate experimental data.
      RESULTS: A significant positive correlation was observed between K? , MK and R2 *
      = 1/T2 *, suggesting that Deltachi (H2O-TISSUE) could be a source of DKI
      contrast. In this view, K? and MK-map contrasts in human WM would not just be due
      to different restricted diffusion processes of compartmentalized water but also
      to local Deltachi (H2O-TISSUE) . However, MC simulations show a strong dependence
      on microstructure rearrangement and a feeble dependence on Deltachi (H2O-TISSUE)
      of DKI signal. CONCLUSION: Our results suggests a concomitant and complementary
      existence of multi-compartmentalized diffusion process and Deltachi (H2O-TISSUE)
      in DKI contrast that might explain why kurtosis contrast is more sensitive than
      DTI in discriminating between different tissues. However, more realistic
      numerical simulations are needed to confirm this statement.

PMID- 24894846
TI  - Serendipity and success: Asahi Prize awarded for discovery of dementia with Lewy
      bodies.

PMID- 24894848
TI  - Radiation within urology: challenges and triumphs.

PMID- 24894849
TI  - Remembering the contributions of two New Zealand greats: Bill Utley and Donald
      Urquart-Hay.

PMID- 24894847
TI  - Peritumoral epilepsy: relating form and function for surgical success.
AB  - Seizures are a prominent symptom in patients with both primary and secondary
      brain tumors. Medical management of seizure control in this patient group is
      problematic as the mechanisms linking tumorigenesis and epileptogenesis are
      poorly understood. It is possible that several mechanisms contribute to tumor
      associated epileptic zone formation. In this review, we discuss key candidates
      that may be implicated in peritumoral epileptogenesis and, in so doing, hope to
      highlight areas for future research. Furthermore, we summarize the current role
      of antiepileptic medications in this type of epilepsy and examine the changes in
      surgical practice which may lead to improved seizure rates after tumor surgery.
      Lastly, we speculate on possible future preoperative and intraoperative
      considerations for improving seizure control after tumor resection.

PMID- 24894850
TI  - A Phase III trial to investigate the timing of radiotherapy for prostate cancer
      with high-risk features: background and rationale of the Radiotherapy -- Adjuvant
      Versus Early Salvage (RAVES) trial.
AB  - OBJECTIVES: To test the hypothesis that observation with early salvage
      radiotherapy (SRT) is not inferior to 'standard' treatment with adjuvant RT (ART)
      with respect to biochemical failure in patients with pT3 disease and/or positive
      surgical margins (SMs) after radical prostatectomy (RP). To compare the following
      secondary endpoints between the two arms: patient-reported outcomes, adverse
      events, biochemical failure-free survival, overall survival, disease-specific
      survival, time to distant failure, time to local failure, cost utility analysis,
      quality adjusted life years and time to androgen deprivation. PATIENTS AND
      METHODS: The Radiotherapy - Adjuvant Versus Early Salvage (RAVES) trial is a
      phase III multicentre randomised controlled trial led by the Trans Tasman
      Radiation Oncology Group (TROG), in collaboration with the Urological Society of
      Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital
      and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be
      randomised 1:1 to either ART commenced at <=4 months of RP (standard of care) or
      close observation with early SRT triggered by a PSA level of >0.20 ng/mL
      (experimental arm). Eligible patients have had a RP for adenocarcinoma of the
      prostate with at least one of the following risk factors: positive SMs +/-
      extraprostatic extension +/- seminal vesicle involvement. The postoperative PSA
      level must be <=0.10 ng/mL. Rigorous investigator credentialing and a quality
      assurance programme are designed to promote consistent RT delivery among
      patients. RESULTS: Trial is currently underway, with 258 patients randomised as
      of 31 October 2013. International collaborations have developed, including a
      planned meta-analysis to be undertaken with the UK Medical Research
      Council/National Cancer Institute of Canada Clinical Trials Group RADICALS
      (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial
      and an innovative psycho-oncology sub-study to investigate a patient decision aid
      resource. CONCLUSION: On the current evidence available, it remains unclear if
      ART is equivalent or superior to observation with early SRT.

PMID- 24894852
TI  - Expression and function of gastrin-releasing peptide (GRP) in normal and
      cancerous urological tissues.
AB  - Gastrin-releasing peptide (GRP) acts as an important regulatory peptide in
      several normal physiological processes and as a growth factor in certain cancers.
      In this review we provide a comprehensive overview of the current state of
      knowledge of GRP in urological tissues under both normal and cancerous
      conditions. GRP and its receptor, GRP-R, are expressed in the normal kidney and
      renal cancers. GRP can stimulate the growth of renal cancer cells. GRP and GRP-R
      are expressed in prostate cancer and GRP can stimulate the growth of prostate
      cancer cell lines. Importantly, GRP is a key neuroendocrine peptide, which may be
      involved in the progression of advanced prostate cancer and in the neuroendocrine
      differentiation of prostate cancer. Recent animal studies have shown that GRP and
      GRP-R are an integral part of male sexual function and play a crucial role in
      spinal control of erections and ejaculation. 

PMID- 24894851
TI  - Fiducial markers and spacers in prostate radiotherapy: current applications.
AB  - OBJECTIVES: To review the use of fiducial markers and spacers in prostate
      radiotherapy (RT). MATERIALS AND METHODS: We reviewed the literature on the use
      of fiducial markers to improve accuracy in delivery of RT for prostate cancer. We
      discuss the rationale for fiducials, the types available, the procedures and
      complications. We also reviewed the current literature on the novel use of
      spacers to reduce rectal toxicity during prostate irradiation. RESULTS: Prostate
      motion is a significant problem both during and between RT treatments.
      Intraprostatic fiducials allow accurate prostate localisation ensuring RT
      treatment accuracy. Insertion of gold fiducials are a cost-effective marker that
      can be easily and quickly implanted and at least three fiducials are recommended.
      Severe complications from fiducial implantation are uncommon and marker migration
      is very rarely clinically significant. Spacers are a novel method to distance the
      rectum from the prostate during RT, reducing acute rectal toxicity, and have no
      detrimental impact on health-related quality of life. CONCLUSIONS: Intraprostatic
      fiducials are now standard of care when delivering prostate RT and early data
      shows benefit of spacers in reducing RT rectal toxicity.

PMID- 24894853
TI  - Anxiety and health-related quality of life (HRQL) in patients undergoing active
      surveillance of prostate cancer in an Australian centre.
AB  - OBJECTIVE: To assess anxiety, health-related quality of life (HRQL) and
      understanding of active surveillance (AS) in a cohort of patients enrolled in AS
      of prostate cancer in an Australian setting. PATIENTS AND METHODS: Survey of 61
      men currently enrolled in AS for prostate cancer, which included validated
      measures of sexual function using the International Index of Erectile Function
      (IIEF-5), voiding using the International Prostate Symptom Severity Score (IPSS)
      and the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), a measure of
      prostate cancer specific anxiety. Three novel questions to assess patients'
      Understanding of AS (UAS). IIEF-5 and IPSS scores obtained through the present
      survey were compared with patients' scores at initiation of AS. RESULTS: In all,
      47 of 61 (77%) patients responded to the survey. There was no significant
      difference in patients' IIEF-5 and IPSS scores at commencement of AS compared
      with the survey results. Our patients' on AS MAX-PC scores were consistent with
      other published cohorts and did not suggest high rates of clinically significant
      anxiety amongst this cohort. Most (89%) of the patients' responses to the UAS
      indicated a correct understanding of AS. CONCLUSION: Our patients on AS
      maintained their HRQL with low levels of anxiety, which did not differ from those
      reported in other groups of men with prostate cancer and most had an appropriate
      understanding of AS. This study represents one of the first Australasian
      investigations on HRQL and anxiety in men on AS of prostate cancer.

PMID- 24894854
TI  - Ertapenem prophylaxis reduces sepsis after transrectal biopsy of the prostate.
AB  - OBJECTIVE: To prospectively trial ertapenem prophylaxis in patients with known
      risk factors of sepsis undergoing transrectal biopsy of the prostate. PATIENTS
      AND METHODS: In this prospective audit, patients were identified as having a low-
      or high-risk of sepsis based on a questionnaire about established risk factors:
      previous biopsy; recurrent urine infections; receiving ciprofloxacin in the 12
      months prior; travel to South-East Asia or South America in the previous 6
      months; or diabetes, immune system impairment or receipt of immunosuppressant
      drugs. All received ciprofloxacin and amoxicillin-clavulanate and high-risk
      patients additionally received ertapenem. Sepsis requiring hospital admission was
      recorded. Data was analysed using a two-tailed Fisher's exact test. RESULTS: In
      all, 80 men were identified as high risk of sepsis and 90 as low risk during the
      audit period. Six patients in the low-risk group (6.7%, 95% confidence interval
      2.1-11.3) and none in the high-risk group developed sepsis (P = 0.03). Of the six
      developing sepsis, two grew ciprofloxacin-resistant organisms, two had no growth
      and two grew a ciprofloxacin-sensitive organism, although one of these grew
      extended-spectrum beta-lactamase-producing Escherichia coli. CONCLUSION: The
      addition of ertapenem to standard prophylaxis is effective at reducing sepsis
      after prostate biopsy. Risk stratification is not effective at identifying those
      men at low risk of sepsis, as these men still have a high sepsis rate. Ertapenem
      prophylaxis for all patients undergoing prostate biopsy is likely to be the most
      effective strategy in our population group.

PMID- 24894856
TI  - [Clinical impact of peripheral lymphocyte counts for metastatic urothelial
      carcinoma patients treated with chemotherapy].
AB  - Pre-chemotherapeutic factors to assess the prognosis of patients with advanced
      urothelial carcinoma have not yet been completely established. The immune
      response of the host to the tumor is lymphocyte dependent. However, the effect of
      lymphocytes on chemotherapy prognosis is unknown. In this study, we investigated
      the correlation between pre-chemotherapeutic lymphocyte counts and the clinical
      characteristics of urothelial carcinoma and determined the effectiveness of
      lymphocytes as a prognostic predictor for metastatic urothelial carcinoma treated
      with chemotherapy. Between April 2003 and March 2011, data from 34 patients with
      unresectable or metastatic urothelial carcinoma were retrospectively subjected to
      multivariate regression analysis to determine the patient characteristics with
      independent prognostic significance for survival. The median patient age was 71 ;
      21 patients were male and 13 female. The number of primary tumors in the pelvis,
      ureter, and bladder were four, six, and 24, respectively. Seventeen patients
      underwent prior curative resections, and visceral metastases at chemotherapy were
      detected in 14 patients. The median lymphocyte count at chemotherapy was
      1,292/ml. Cancer-specific survival was significantly lower in patients with
      lymphocyte counts <1,000/ml than in patients with lymphocyte counts >=1,000/MUl
      (p=0. 001). During multivariate analysis, visceral metastasis and lymphocyte
      counts were independent factors for predicting poor prognosis. In addition,
      lymphocyte counts of <1, 000/ml or positive visceral metastases also affected
      survival. This information may be useful for identifying patients who are likely
      to benefit from chemotherapy.

PMID- 24894855
TI  - [The safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week
      off) for treatment of metastatic renal cell carcinoma].
AB  - We prospectively investigated the safety and efficacy of sunitinib using a
      modified regimen (2 weeks on/1 week off) in 24 patients (22 males, 2 females ;
      age range 39-86 years, median 64 years) with metastatic renal cell carcinoma
      (RCC). During the observation period (3-62 weeks, median 21 weeks),
      thrombocytopenia was seen in 13 (54.2%), leukopenia in 11 (45.8%), hand-foot
      syndrome in 5 (20.8%), hypertension in 4 (16.7%), and hypothyroidism in 3 (12.5%)
      patients, while grade 3 or higher adverse events were found in 4 (16.7%), 1
      (4.2%), 1 (4.2%), 2 (8.3%), and 0 patients, respectively. Of the 21 patients
      evaluable for response, 5 (23. 8%) showed partial response, 8 (38.1%) stable
      disease, and 8 (38.1%) progressive disease. This new modified regimen may lead to
      a reduction in adverse events for treatment of patients with metastatic RCC as a
      substitute for the standard dosing regimen of sunitinib.

PMID- 24894857
TI  - [Small cell carcinoma of the bladder].
AB  - We retrospectively reviewed the records of 11 patients with small cell carcinoma
      of the bladder, who were diagnosed at Kyoto University Hospital between June 1995
      and November 2010. The median age was 79 years. Two patients had stage I disease,
      4 had stage II disease, 2 had stage III disease, and 3 had stage IV disease. All
      3 patients with stage IV disease had metastatic disease. They had very poor
      prognosis with a median survival of only 9.1 months (range 3.2-13.0 months). Of 8
      patients without metastatic disease, 3 patients who had been treated with
      neoadjuvant chemotherapy followed by cystectomy had longterm survival. The median
      survival of these 3 patients was 85.5 months (range 38.0-102.8 months), and all
      of them are still alive without cancer. The median survival of the other 5
      patients was 12.6 months (range 9. 9-33. 8 months). There were significant
      differences in survival between patients with neoadjuvant chemotherapy followed
      by cystectomy and with other treatments (p=0.024). In conclusion, these results
      suggested that neoadjuvant chemotherapy followed by cystectomy could cure
      patients with small cell carcinoma of the bladder without metastatic disease.

PMID- 24894858
TI  - [Significance of the antimicrobial drug used to prevent febrile infection
      following prostate needle biopsy].
AB  - The rate of incidence of febrile infection and the antimicrobial drug used at the
      time of prostate needle biopsy was examined retrospectively. SPFX (sparfloxacin)
      400 mg (January 2007 to March 2010) and LVFX (levofloxacin) 500 mg (April 2010,
      onward) were administered prophylactically in 1,034 patients undergoing
      transrectal or transperineal prostate biopsy. One febrile infection occurred and
      resolved in each group. A single dose of LVFX 500 mg before the procedure
      effectively prevented febrile infection in both transrectal and transperineal
      prostate needle biopsy.

PMID- 24894859
TI  - [Renal pelvic tumor with difficult radiological diagnosis : a report of two
      cases].
AB  - Case 1 : A 60-year-old man presented with right flank pain. A computed tomography
      (CT) scan revealed a large right renal tumor, multiple lung metastases, multiple
      liver metastases, and tumor thrombus of the right renal vein. These findings were
      strongly suggestive of renal cell carcinoma. The patient suddenly complained of
      dyspnea at night due to bilateral pulmonary embolism, and the patient died 11
      days after onset. Needle necropsy showed that the tumors were squamous cell
      carcinomas of the renal pelvis. Case 2 : A 66-year-old man presented with
      macrohematuria. An abdominal CT scan revealed a right renal mass and liver
      metastasis. The differential diagnosis was between renal cell carcinoma and
      urothelial carcinoma. A renal biopsy revealed urothelial carcinoma of the renal
      pelvis. The patient died of the disease 3 months after initiation of chemotherapy
      with gemcitabine and cisplatin. We report these 2 cases to emphasize the
      importance of renal biopsy and thorough histological analysis for the
      determination of treatment strategies against unresectable renal tumors. 

PMID- 24894860
TI  - [A case of lung abscess during chemotherapy for testicular tumor].
AB  - 32-year-old man was seen in a clinic because of prolonged cough and slight-fever.
      Chest X-ray showed multiple pulmonary nodules, and multiple lung and mediastinal
      lymph node metastases from right testicular tumor was suspected by positron
      emission tomography/CT (PET/CT) scan. He was diagnosed with right testicular germ
      cell tumor (embryonal carcinoma + seminoma, pT2N1M1b), and classified into the
      intermediate risk group according to International Germ Cell Cancer Collaborative
      Group. He underwent 4 cycles of chemotherapy with bleomycin, etoposide and
      cisplatin (BEP therapy). During BEP therapy, sputum with foul odor appeared and
      chest CT scan revealed lung abscess with a necrotic lesion of metastatic tumor.
      The lung abscess was treated successfully with antibiotics.

PMID- 24894861
TI  - [A case of giant testicular tumor in a schizophrenic patient].
AB  - A 55-year-old man with schizophrenia presented with right scrotal enlargement.
      Clinical examination revealed a right adult -head-sized testicular tumor,
      multiple lymph node metastasis with marked elevation of serum lactic
      dehydrogenase (LDH) and beta -human chorionic gonadotropin (beta -HCG). Right
      high orchiectomy followed by chemotherapy with bleomysin, etoposide and cisplatin
      (BEP) for 4 cycles was performed. The tumor weighed 5,270 g, and was
      pathologically diagnosed as seminoma. After the treatment, the tumor markers were
      normalized, but he refused to undergo retroperitoneal lymph node dissection. 

PMID- 24894862
TI  - [A case of solitary neurofibroma of spermatic cord].
AB  - We report a case of solitary neurofibroma of the spermatic cord. A 48-year-old
      man was referred to our hospital with a complaint of a left inguinal mass.
      Magnetic resonance imaging (MRI) demonstrated a solid mass in the left inguinal
      region. The tumor was removed. Histopathological diagnosis was neurofibloma. He
      had no other findings of Von Recklinghausen disease. Only a few cases of solitary
      neurofibromas of spermatic cord have been reported.

PMID- 24894863
TI  - [A case report of progressive penile necrosis].
AB  - The penis is provided with blood by multiple arteries. Penile necrosis is
      uncommon. Penile necrosis sporadically occurs in patients with progressive
      diabetes mellitus and/or end stage renal failure. Penile necrosis is often
      considered a poor prognostic feature. We present a case of penile necrosis in a
      patient with mild diabetes mellitus. 

PMID- 24894864
TI  - Paxillin promotes tumor progression and predicts survival and relapse in oral
      cavity squamous cell carcinoma by microRNA-218 targeting.
AB  - High-risk human papillomavirus (HPV) 16-infected oral cavity squamous cell
      carcinoma (OCSCC) differs significantly from non-HPV-infected OCSCC. However, the
      molecular pathogenesis of HPV-infected OCSCC remains unclear. Paxillin (PXN) has
      been reported to promote lung tumor progression by miR-218 targeting. In
      addition, expression of miR-218 has been shown to be reduced by HPV16 E6 in
      cervical cancer. We thus asked whether PXN can promote tumor progression by E6
      reduced miR-218 in OCSCC, especially in HPV-infected OCSCC. Mechanistic studies
      demonstrated that PXN expression increased markedly upon E6-mediated reductions
      in miR-218, resulting in increased colony formation and invasion capabilities in
      HPV-infected OCSCC cells. Among tumor specimens, HPV16/18 infection was
      negatively associated with miR-218 expression and positively associated with PXN
      expression. Kaplan-Meier and Cox regression models demonstrated that patients
      with low-miR-218 tumors or high-PXN tumors exhibited shorter overall survival
      (OS) and relapse-free survival (RFS) than those with high-miR-218 tumors or low
      PXN tumors. Interestingly, HPV-infected patients with low-miR-218, high-PXN
      tumors and both combinations exhibited the worst OS and RFS compared with
      patients in their counterparts. These observations in patients were consistent
      with the findings from the cell model. Therefore, we suggest that PXN might be
      targeted to suppress tumor progression and consequently to improve outcomes in
      OCSCC, especially in HPV-infected OCSCC. 

PMID- 24894865
TI  - Nuclear adenomatous polyposis coli suppresses colitis-associated tumorigenesis in
      mice.
AB  - Mutation of tumor suppressor adenomatous polyposis coli (APC) initiates most
      colorectal cancers and chronic colitis increases risk. APC is a nucleo
      cytoplasmic shuttling protein, best known for antagonizing Wnt signaling by
      forming a cytoplasmic complex that marks beta-catenin for degradation. Using our
      unique mouse model with compromised nuclear Apc import (Apc(mNLS)), we show that
      Apc(mNLS/mNLS) mice have increased susceptibility to tumorigenesis induced with
      azoxymethane (AOM) and dextran sodium sulfate (DSS). The AOM-DSS-induced colon
      adenoma histopathology, proliferation, apoptosis, stem cell number and beta
      catenin and Kras mutation spectra were similar in Apc(mNLS/mNLS) and Apc(+/+)
      mice. However, AOM-DSS-treated Apc(mNLS/mNLS) mice showed more weight loss, more
      lymphoid follicles and edema, and increased colon shortening than treated
      Apc(+/+) mice, indicating a colitis predisposition. To test this directly, we
      induced acute colitis with a 7 day DSS treatment followed by 5 days of recovery.
      Compared with Apc(+/+) mice, DSS-treated Apc(mNLS/mNLS) mice developed more
      severe colitis based on clinical grade and histopathology. Apc(mNLS/mNLS) mice
      also had higher lymphocytic infiltration and reduced expression of stem cell
      markers, suggesting an increased propensity for chronic inflammation. Moreover,
      colons from DSS-treated Apc(mNLS/mNLS) mice showed fewer goblet cells and reduced
      Muc2 expression. Even in untreated Apc(mNLS/mNLS) mice, there were significantly
      fewer goblet cells in jejuna, and a modest decrease in colonocyte Muc2 expression
      compared with Apc(+/+) mice. Colonocytes from untreated Apc(mNLS/mNLS) mice also
      showed increased expression of inflammatory mediators cyclooxygenase-2 (Cox-2)
      and macrophage inflammatory protein-2 (MIP-2). These findings reveal novel
      functions for nuclear Apc in goblet cell differentiation and protection against
      inflammation-induced colon tumorigenesis. 

PMID- 24894868
TI  - Color Doppler Evaluation of the Retrobulbar Hemodynamic Changes in Chronic
      Obstructive Pulmonary Disease: COPD and Retrobulbar Hemodynamic Changes.
AB  - The aim of this study was to evaluate the hemodynamic changes in the extraocular
      orbital vessels of the patients with chronic obstructive pulmonary disease
      (COPD), using color Doppler ultrasonography, and to compare the results with
      those of healthy control subjects. The control group consisted of 35 healthy
      subjects who had no systemic problems, while the study group consisted of 60
      patients with the diagnosis of COPD. Patients with COPD were grouped according to
      the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Twenty
      patients of stage 1 COPD (mild airflow limitation), stage 2 COPD (moderate
      airflow limitation), or stage 3 COPD (severe airflow limitation) were included in
      the groups 1, 2, and 3, respectively. Measurements were performed in both eyes of
      each participant. Peak systolic velocity (PSV), end-diastolic velocity (EDV),
      resistance index (RI), and pulsatility index (PI) were measured in the ophthalmic
      artery (OA), central retinal artery (CRA), and posterior ciliary artery (PCA).
      The RI and PI measurements of the OA, CRA, and PCA were significantly higher in
      group 3 when compared to the control group and groups 1 and 2. These
      significances were not observed when PSV and EDV values were compared. There were
      also no significant differences between groups 1, 2, and control patients, when
      mean PSV, EDV, RI, and PI values of all arteries were compared. None of the above
      parameters showed statistical significance when mean RI, PI, PSV, and EDV were
      compared between left and right eyes. Severe (stage 3) COPD is associated with
      impaired retrobulbar hemodynamics. Increased hypoxia and vascular mediators may
      be suggested in etiology.

PMID- 24894867
TI  - Computer-Aided Strain Evaluation for Acoustic Radiation Force Impulse Imaging of
      Breast Masses.
AB  - Acoustic radiation force impulse (ARFI) is a newly developed elastography
      technique that uses acoustic radiation force to provide additional stiffness
      information to conventional sonography. A computer-aided diagnosis (CAD) system
      was proposed to automatically specify the tumor boundaries in ARFI images and
      quantify the statistical stiffness information to reduce user dependence. The
      level-set segmentation was used to delineate tumor boundaries in B-mode images,
      and the segmented boundaries were then mapped to the corresponding area in ARFI
      images for a gray-scale calculation. A total of 61 benign and 51 malignant tumors
      were evaluated in the experiment. The CAD system based on the proposed ARFI
      features achieved an accuracy of 80% (90/112), a sensitivity of 80% (41/51), and
      a specificity of 80% (49/61), which is significantly better than that of the
      quantitative B-mode features (p < 0.05). The ARFI features were further combined
      with the B-mode features, including shape and texture features, to further
      improve performance (area under the curve [AUC], 0.90 vs. 0.86). In conclusion,
      the CAD system based on the proposed ARFI features is a promising and efficient
      diagnostic method.

PMID- 24894869
TI  - 39th International Symposium on Ultrasonic Imaging and Tissue Characterization.

PMID- 24894866
TI  - Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of
      NRF2-mediated protective pathways.
AB  - The importance of estrogens in the etiology of breast cancer is widely
      recognized. Estrogen-induced oxidative stress has been implicated in this
      carcinogenic process. Resveratrol (Res), a natural antioxidant phytoestrogen has
      chemopreventive effects against a variety of illnesses including cancer. The
      objective of the present study was to characterize the mechanism(s) of Res
      mediated protection against estrogen-induced breast carcinogenesis. Female August
      Copenhagen Irish rats were treated with 17beta-estradiol (E2), Res and Res + E2
      for 8 months. Cotreatment of rats with Res and E2 inhibited E2-mediated
      proliferative changes in mammary tissues and significantly increased tumor
      latency and reduced E2-induced breast tumor development. Resveratrol treatment
      alone or in combination with E2 significantly upregulated expression of nuclear
      factor erythroid 2-related factor 2 (NRF2) in mammary tissues. Expression of NRF2
      regulated antioxidant genes NQO1, SOD3 and OGG1 that are involved in protection
      against oxidative DNA damage was increased in Res- and Res + E2-treated mammary
      tissues. Resveratrol also prevented E2-mediated inhibition of detoxification
      genes AOX1 and FMO1. Inhibition of E2-mediated alterations in NRF2 promoter
      methylation and expression of NRF2 targeting miR-93 after Res treatment indicated
      Res-mediated epigenetic regulation of NRF2 during E2-induced breast
      carcinogenesis. Resveratrol treatment also induced apoptosis and inhibited E2
      mediated increase in DNA damage in mammary tissues. Increased apoptosis and
      decreased DNA damage, cell migration, colony and mammosphere formation in Res-
      and Res + E2-treated MCF-10A cells suggested a protective role of Res against E2
      induced mammary carcinogenesis. Small-interfering RNA-mediated silencing of NRF2
      inhibited Res-mediated preventive effects on the colony and mammosphere
      formation. Taken together, these results suggest that Res inhibits E2-induced
      breast carcinogenesis via induction of NRF2-mediated protective pathways. 

PMID- 24894871
TI  - Preparation of neuronal co-cultures with single cell precision.
AB  - Microfluidic embodiments of the Campenot chamber have attracted great interest
      from the neuroscience community. These interconnected co-culture platforms can be
      used to investigate a variety of questions, spanning developmental and functional
      neurobiology to infection and disease propagation. However, conventional systems
      require significant cellular inputs (many thousands per compartment), inadequate
      for studying low abundance cells, such as primary dopaminergic substantia nigra,
      spiral ganglia, and Drosophilia melanogaster neurons, and impractical for high
      throughput experimentation. The dense cultures are also highly locally entangled,
      with few outgrowths (<10%) interconnecting the two cultures. In this paper
      straightforward microfluidic and patterning protocols are described which address
      these challenges: (i) a microfluidic single neuron arraying method, and (ii) a
      water masking method for plasma patterning biomaterial coatings to register
      neurons and promote outgrowth between compartments. Minimalistic neuronal co
      cultures were prepared with high-level (>85%) intercompartment connectivity and
      can be used for high throughput neurobiology experiments with single cell
      precision. 

PMID- 24894872
TI  - Hemocompatibility of pseudozwitterionic polymer brushes with a systematic well
      defined charge-bias control.
AB  - In this study, a pseudozwitterionic surface bearing positively and negatively
      mixed charged moieties was developed as a potential hemocompatible material for
      biomedical applications. In this work, hemocompatility of pseudozwitterionic
      surface prepared from copolymerization of negatively charged 3-sulfopropyl
      methacrylate (SA) and positively charged [2-(methacryloyloxy)ethyl]
      trimethylammonium (TMA) was delineated. Mixed charge distribution in the prepared
      poly(TMA-co-SA)-grafted surface can be controlled by regulating TMA and SA
      monomer ratios via surface-initiated atom transfer radical polymerization. The
      effects of grafting composition and charge bias variations on blood compatibility
      of poly(TMA-co-SA)-grafted surface were reported. The protein adsorption on
      different poly(TMA-co-SA)-grafted surfaces from human plasma protein (fibrinogen,
      HSA, and gamma-globulin) solutions was evaluated using an enzyme-linked
      immunosorbent assay. Blood platelet adhesion and time measurements on plasma
      clotting were conducted to determine the platelet activation on the grafted
      surface. It was found that the protein resistance and anti-blood cell adhesion of
      prepared surface can be precisely controlled by controlling the charge balance of
      TMA/SA compositions. In addition, different charge bias variations on the
      poly(TMA-co-SA)-grafted surface would induce electrostatic interactions between
      plasma proteins and prepared surfaces which lead to adsorptions of interfacial
      protein and blood cells, plasma clotting, and blood cell hemolysis. Results from
      this study suggest that the hemocompatility of mixed charged poly(TMA-co-SA)
      grafted surface depends on the charge bias level. This provides a great potential
      for designing biomaterial with unique surface chemical structure which could be
      used in contact with human blood. 

PMID- 24894873
TI  - Two-way traffic of glycoside hydrolase family 18 processive chitinases on
      crystalline chitin.
AB  - Processivity refers to the ability of synthesizing, modifying and degrading
      enzymes to catalyse multiple successive cycles of reaction with polymeric
      substrates without disengaging from the substrates. Since biomass
      polysaccharides, such as chitin and cellulose, often form recalcitrant
      crystalline regions, their degradation is highly dependent on the processivity of
      degrading enzymes. Here we employ high-speed atomic force microscopy to directly
      visualize the movement of two processive glycoside hydrolase family 18 chitinases
      (ChiA and ChiB) from the chitinolytic bacterium Serratia marcescens on
      crystalline beta-chitin. The half-life of processive movement and the velocity of
      ChiA are larger than those of ChiB, suggesting that asymmetric subsite
      architecture determines both the direction and the magnitude of processive
      degradation of crystalline polysaccharides. The directions of processive
      movements of ChiA and ChiB are observed to be opposite. The molecular mechanism
      of the two-way traffic is discussed, including a comparison with the processive
      cellobiohydrolases of the cellulolytic system. 

PMID- 24894870
TI  - Participation of the central melanocortin system in metabolic regulation and
      energy homeostasis.
AB  - Obesity and metabolic disorders, such as type 2 diabetes and hypertension, have
      attracted considerable attention as life-threatening diseases not only in
      developed countries but also worldwide. Additionally, the rate of obesity in
      young people all over the world is rapidly increasing. Accumulated evidence
      suggests that the central nervous system may participate in the development of
      and/or protection from obesity. For example, in the brain, the hypothalamic
      melanocortin system senses and integrates central and peripheral metabolic
      signals and controls the degree of energy expenditure and feeding behavior, in
      concert with metabolic status, to regulate whole-body energy homeostasis.
      Currently, researchers are studying the mechanisms by which peripheral metabolic
      molecules control feeding behavior and energy balance through the central
      melanocortin system. Accordingly, recent studies have revealed that some
      inflammatory molecules and transcription factors participate in feeding behavior
      and energy balance by controlling the central melanocortin pathway, and have thus
      become new candidates as therapeutic targets to fight metabolic diseases such as
      obesity and diabetes. 

PMID- 24894874
TI  - A unique phosphorylation-dependent eIF4E assembly on 40S ribosomes co-ordinated
      by hepatitis C virus protein NS5A that activates internal ribosome entry site
      translation.
AB  - We previously reported that the HCV (hepatitis C virus) protein NS5A up-regulated
      mRNA cap binding eIF4F (eukaryotic initiation factor 4F) complex assembly through
      mTOR (mechanistic target of rapamycin)-4EBP1 (eIF4E-binding protein 1) pathway
      and that NS5A (non-structural protein 5A) physically interacted with translation
      apparatus. In the present study, we demonstrate that NS5A co-ordinates a unique
      assembly of the cap binding protein eIF4E and 40S ribosome to form a complex that
      we call ENR (eIF4E-NS5A-ribosome). Recruitment of NS5A and eIF4E to 40S ribosome
      was confirmed by polysome fractionation, subcellular fractionation and high-salt
      wash immunoprecipitation. These observations were also confirmed in HCV-infected
      cells, validating its biological significance. eIF4E phosphorylation was critical
      for ENR assembly. 80S ribosome dissociation and RNase integrity assays revealed
      that, once associated, the ENR complex is stable and RNA interaction is
      dispensable. Both the N- and C-terminal regions of NS5A domain 1 were
      indispensable for this assembly and for the NS5A-induced HCV IRES (internal
      ribosome entry site) activation. The present study demonstrates that NS5A
      initially associates with phosphorylated eIF4E of eIF4F complex and subsequently
      recruits it to 40S ribosomes. This is the first time the interaction of viral
      protein with both eIF4E and ribosomes has been reported. We propose that this
      assembly would determine the outcome of HCV infection and pathogenesis through
      regulation of viral and host translation. 

PMID- 24894876
TI  - Application of Heideggerian phenomenology to mentorship of nursing students.
AB  - AIM: To discuss interpretations of the lived experience of mentoring based on
      Heidegger's concept of dasein. The focus is on one main theme identified in an in
      depth study of the lived experience of nurses mentoring students in their
      workplace: a world of hope for the nursing profession. BACKGROUND: This article
      focuses on dasein's 'existence', which is temporally aligned with having a
      future. Data relating to this theme are presented and interpreted with respect to
      the temporal aspect of dasein pertaining to 'having a future' and the
      Heideggerian existentials of existence and verstehen (understanding). DESIGN: The
      research design was based on hermeneutic phenomenology, exploring the mentors'
      'being'. METHODS: Data were gathered during 2008 through hermeneutic interviews,
      event diaries and participant drawings. Analysis occurred through sustained
      hermeneutic engagement with the data and application of an interpretive lens
      provided by Heidegger's care structure. RESULTS: Three sub-themes are identified:
      'being a gatekeeper', 'sustaining a professional will', and 'passing on the
      special things'. CONCLUSIONS: Mentors can and need to engage on a deep personal
      level with their students if they are to intervene appropriately as gatekeepers
      to the profession.

PMID- 24894875
TI  - Digital holographic microscopy and focusing methods based on image sharpness.
AB  - Digital holographic microscope allows imaging of opaque and transparent specimens
      without staining. A digitally recorded hologram must be reconstructed numerically
      at the actual depth of the object to obtain a focused image. We have developed a
      high-resolution digital holographic microscope for imaging amplitude and phase
      objects with autofocusing capability. If the actual depth of an object is not
      known a priori, it is estimated by comparing the sharpness of several
      reconstructions at different distances, which is very demanding in means of
      computational power when the recorded hologram is large. In this paper, we
      present 11 different sharpness metrics for estimating the actual focus depths of
      objects. The speed performance of focusing is discussed, and a scaling technique
      is introduced where the speed of autofocusing increases on the order of square of
      the scale ratio. We measured the performance of scaling on computer-generated
      holograms and on recorded holograms of a biological sample. We show that
      simulations are in good agreement with the experimental results. 

PMID- 24894877
TI  - Thermally switchable aligned nanopores by magnetic-field directed self-assembly
      of block copolymers.
AB  - A scalable approach for developing large area polymer films, with stimuli
      responsive vertically aligned nanopores is reported. Magnetic fields are used to
      create highly aligned hexagonally packed block copolymer cylindrical microdomains
      with order parameters exceeding 0.95. Selective etch removal of material yields
      nanoporous films which demonstrate reversible pore closure on heating. 

PMID- 24894878
TI  - Inhibition of infection-mediated preterm birth by administration of broad
      spectrum chemokine inhibitor in mice.
AB  - Preterm birth (PTB) is the single most important cause of perinatal and infant
      mortality worldwide. Maternal infection can result in PTB. We investigated the
      ability of a Broad Spectrum Chemokine Inhibitor (BSCI) to prevent infection
      induced PTB in mice. PTB was initiated in pregnant mice by intraperitoneal
      injection of lipopolysaccharide (LPS; 50 MUg). Half the mice received BSCI (10
      mg/kg) 24 hrs prior to and immediately before LPS administration. The impact of
      LPS alone or LPS plus BSCI was assessed on (i) injection-to-delivery interval,
      foetal survival rate, placental and neonates' weight; (ii) amniotic fluid and
      maternal plasma cytokine levels (by Luminex assay); foetal and maternal tissue
      cytokine gene expression levels (by Real-Time RT-PCR); (iii) immune cells
      infiltration into the uterine tissue (by stereological immunohistochemistry). Pre
      treatment with BSCI (i) decreased LPS-induced PTB (64% versus 100%, P < 0.05);
      (ii) significantly attenuated cytokine/chemokine expression in maternal tissues
      (plasma, liver, myometrium, decidua); (iii) significantly decreased neutrophil
      infiltration in the mouse myometrium. BSCI-treated mice in which PTB was delayed
      till term had live foetuses with normal placental and foetal weight. BSCI
      represents a promising new class of therapeutics for PTB. In a mouse model of
      preterm labour, BCSI suppresses systemic inflammation in maternal tissues which
      resulted in the reduced incidence of LPS-mediated PTB. These data provide support
      for efforts to target inflammatory responses as a means of preventing PTB.

PMID- 24894880
TI  - Psychiatric patients' preferences and experiences in clinical decision-making:
      examining concordance and correlates of patients' preferences.
AB  - OBJECTIVE: To assess the concordance between patients' preferred role in clinical
      decision-making and the role they usually experience in their psychiatric
      consultations and to analyze the influence of socio-demographic, clinical and
      personality characteristics on patients' preferences. METHODS: 677 consecutive
      psychiatric outpatients were invited to participate in a cross-sectional survey
      and 507 accepted. Patients completed Control Preference Scale twice consecutively
      before consultation, one for their preferences of participation and another for
      the style they usually experienced until then, and locus of control and self
      efficacy scales. RESULTS: Sixty-three percent of psychiatric outpatients
      preferred a collaborative role in decision-making, 35% preferred a passive role
      and only a 2% an active one. A low concordance for preferred and experienced
      participation in medical decision-making was registered, with more than a half of
      patients wanting a more active role than they actually had. Age and doctors'
      health locus of control orientation were found to be the best correlates for
      participation preferences, while age and gender were for experienced. Psychiatric
      diagnoses registered significant differences in patients' preferences of
      participation but no concerning experiences. CONCLUSION: The limited concordance
      between preferred and experienced roles in psychiatric patients is indicative
      that clinicians need to raise their sensitivity regarding patient's
      participation. PRACTICE IMPLICATIONS: The assessment of patient's attribution
      style should be useful for psychiatrist to set objectives and priority in the
      communication with their patients.

PMID- 24894879
TI  - Fixation time is a sensitive measure of cocaine cue attentional bias.
AB  - BACKGROUND AND AIMS: Attentional bias has been demonstrated to a variety of
      substances. Evidence suggests that fixation time is a more direct measure of
      attentional bias than response time. The aims of this experiment were to
      demonstrate that fixation time during the visual probe task is a sensitive and
      stable measure of cocaine cue attentional bias in cocaine-using adults compared
      to controls. DESIGN: A between-subject, repeated-measures experiment. SETTING: An
      out-patient research unit. PARTICIPANTS: Fifteen cocaine using and 15 non-cocaine
      using adults recruited from the community. MEASUREMENTS: Participants completed a
      visual probe task with eye tracking and a modified Stroop during two experimental
      sessions. FINDINGS: A significant interaction between cue type and group (F =
      13.5; P < 0.05) indicated that cocaine users, but not controls, displayed an
      attentional bias to cocaine-related images as measured by fixation time. There
      were no changes in the magnitude of attentional bias across sessions (F = 3.4; P
      > 0.05) and attentional bias correlated with self-reported life-time cocaine use
      (r = 0.64, P < 0.05). Response time on the visual probe (F = 1.1; P > 0.05) as
      well as on the modified Stroop (F = 0.1; P > 0.05) failed to detect an
      attentional bias. CONCLUSIONS: Fixation time on cocaine-related stimuli
      (propensity to remain focused on the stimulus) is a sensitive and stable measure
      of cocaine cue attentional bias in cocaine-using adults.

PMID- 24894882
TI  - Cerebellar-thalamic connectivity in schizophrenia.

PMID- 24894883
TI  - Impact of antipsychotic treatment on attention and motor learning systems in
      first-episode schizophrenia.
AB  - BACKGROUND: Antipsychotic medications have established clinical benefit, but
      there are few neuroimaging studies before and after initiating antipsychotic
      medication to assess drug influence on brain circuitry. Attention and motor
      learning tasks are promising approaches for examining treatment-related changes
      in frontostriatal systems. METHODS: Twenty-one unmedicated first-episode
      schizophrenia patients (14 antipsychotic-naive) participated in functional
      imaging studies while performing visual attention (prosaccades) and motor
      learning tasks (predictive saccades). Posttreatment testing was completed in 14
      patients after 4-6 weeks of antipsychotic treatment. Matched healthy controls
      were studied in parallel. RESULTS: Pretreatment, patients had reduced activation
      in the dorsal neocortical visual attention network. Activation deficits were
      significantly reduced posttreatment. Higher medication dose was associated with
      greater caudate activation at follow-up. For the motor learning task, patients'
      dorsolateral prefrontal cortex (DLPFC) was unimpaired prior to treatment but
      showed significantly reduced activation after treatment. CONCLUSION: Impairments
      in dorsal cortical attention networks are present in untreated first-episode
      schizophrenia patients. These impairments are reduced after antipsychotic
      treatment, suggesting a beneficial effect on neural systems for attention.
      Treatment-emergent decreases in DLPFC activation observed for the motor learning
      task are consistent with other clinical and preclinical evidence suggesting that
      antipsychotics can have adverse effects on prefrontal function.

PMID- 24894885
TI  - New conserved structural fields for supercooled liquids.
AB  - By considering Voronoi tessellations of the configurations of a fluid, we propose
      two new conserved fields, which provide structural information not fully
      accounted for by the usual 2-point density correlation functions. One of these
      fields is scalar and associated with the volume of the Voronoi cell, whereas the
      other one, termed the "geometric polarisation", is vectorial and related to the
      local anisotropy of the configurations. We study the static and dynamical
      properties of these fields in the supercooled regime of a model glass-forming
      liquid. We show that the geometric polarisation is statically correlated to the
      force field, but contrary to it develops a plateau regime when the temperature is
      lowered. This different relaxation is related to the cage effect in glass-forming
      liquids, which prevents a complete relaxation of the shape of the cage around
      particle on intermediate time scales. 

PMID- 24894886
TI  - Horizontal deflection of single particle in a paramagnetic fluid.
AB  - This paper describes the horizontal deflection behaviour of a single particle in
      paramagnetic fluids under a high-gradient superconducting magnetic field. A glass
      box was designed to carry out experiments and test assumptions. It was found that
      the particles were deflected away from the magnet bore centre and particles with
      different density and/or susceptibility settled at a certain position on the
      container floor due to the combined forces of gravity and magneto-Archimedes as
      well as lateral buoyant (displacement) force. Matlab was chosen to simulate the
      movement of the particle in the magnetic fluid, the simulation results were in
      good accordance with experimental data. The results presented here, though, are
      still very much in their infancy, which could potentially form the basis of a new
      approach to separating materials based on a combination of density and
      susceptibility. 

PMID- 24894884
TI  - Brain structure correlates of urban upbringing, an environmental risk factor for
      schizophrenia.
AB  - Urban upbringing has consistently been associated with schizophrenia, but which
      specific environmental exposures are reflected by this epidemiological
      observation and how they impact the developing brain to increase risk is largely
      unknown. On the basis of prior observations of abnormal functional brain
      processing of social stress in urban-born humans and preclinical evidence for
      enduring structural brain effects of early social stress, we investigated a
      possible morphological correlate of urban upbringing in human brain. In a sample
      of 110 healthy subjects studied with voxel-based morphometry, we detected a
      strong inverse correlation between early-life urbanicity and gray matter (GM)
      volume in the right dorsolateral prefrontal cortex (DLPFC, Brodmann area 9).
      Furthermore, we detected a negative correlation of early-life urbanicity and GM
      volumes in the perigenual anterior cingulate cortex (pACC) in men only. Previous
      work has linked volume reductions in the DLPFC to the exposure to psychosocial
      stress, including stressful experiences in early life. Besides, anatomical and
      functional alterations of this region have been identified in schizophrenic
      patients and high-risk populations. Previous data linking functional
      hyperactivation of pACC during social stress to urban upbringing suggest that the
      present interaction effect in brain structure might contribute to an increased
      risk for schizophrenia in males brought up in cities. Taken together, our results
      suggest a neural mechanism by which early-life urbanicity could impact brain
      architecture to increase the risk for schizophrenia. 

PMID- 24894887
TI  - Natriuretic peptide receptor A as a novel target for cancer.
AB  - The receptor for the cardiac hormone atrial natriuretic peptide (ANP),
      natriuretic peptide receptor A (NPR-A), has been reported to be expressed in lung
      cancer, prostate cancer and ovarian cancer. NPR-A expression and signaling is
      important for tumor growth; its deficiency protects C57BL/6 mice from lung, skin
      and ovarian cancers. This suggests that NPR-A is a new marker and a new target
      for cancer therapy. Recently, NPR-A has been demonstrated to be expressed in pre
      implantation embryos and in embryonic stem cells, which has a novel role in the
      maintenance of self-renewal and pluripotency of embryonic stem cells. A
      nanoparticle-formulated interfering RNA for NPR-A attenuated B16 melanoma tumors
      in mice. Ectopic expression of a plasmid encoding NP73-102, the NH2-terminal
      peptide of the ANP prohormone which downregulates NPR-A expression, also
      suppressed lung metastasis of A549 cells in nude mice and tumorigenesis of Line 1
      cells in immunocompetent BALB/c mice. These results suggest that NPR-A is
      involved in tumorigenesis and a new target for cancer therapy. This review
      focuses on structure, abnormal functions and carcinogenic mechanisms of NPR-A to
      investigate its role in tumorigenesis. 

PMID- 24894888
TI  - Perioperative Pregabalin for Acute Pain After Gynecological Surgery: A Meta
      analysis.
AB  - BACKGROUND: Pregabalin has been used as an adjuvant in some trials to control
      postoperative pain after gynecologic surgery. However, the potential clinical
      advantage remains debatable. OBJECTIVE: We performed a meta-analysis of clinical
      trials of pregabalin to evaluate its ability to control acute postoperative pain
      after gynecologic surgery. METHODS: We searched PubMed, ScienceDiret, and the
      Cochrane Library of Randomized Controlled Trials up to January 2014. We performed
      a systematic review and meta-analysis of prospective controlled studies reporting
      pregabalin for gynecologic surgery. The primary outcome was pain outcomes and
      postoperative cumulative opioid consumption. Data were reported as weighted mean
      differences (WMDs) and 95% CIs. The secondary outcome was adverse effects after
      surgery. RESULTS: Six valid randomized trials met the eligibility criteria and
      were included in the meta-analysis. Pooled data were collected from 452 patients
      between 2007 and 2012 (These trials were separately conducted in Greece 2012,
      India 2011-2012, Turkey 2011, Denmark 2009 and Australia 2007). The pregabalin
      treated patients consumed fewer opioids during the first 24 hours postoperatively
      (WMD, -8.50 mg; 95% CI, -11.29 to -5.71 mg; P < 0.00001). Pain intensity at rest
      and on movement or coughing revealed a statistically significant pain relief
      effect of pregabalin during 24 hours postoperatively (at rest: WMD, -6.20 mm; 95%
      CI, -11.83 to -0.58 mm; P = 0.03; on movement or coughing: WMD, -5.32 mm; 95% CI,
      -9.73 to -0.91 mm; P = 0.02). No differences were found between the pregabalin
      and control groups for the adverse effects. CONCLUSIONS: Pregabalin has an
      analgesic and opioid-sparing effect and does not increase the frequency of
      adverse effects in acute postoperative pain management after gynecologic surgery.

PMID- 24894889
TI  - Epidemiology and costs of diabetes mellitus in Switzerland: an analysis of health
      care claims data, 2006 and 2011.
AB  - BACKGROUND: Quantifying the burden of diabetes mellitus is fundamental for
      managing patients in health service delivery systems and improves the
      understanding of the importance of prevention and early intervention of diabetes.
      In Switzerland, epidemiological data on diabetes are very scarce. In this study
      we provide a first national overview of the current situation of diabetes
      mellitus in Switzerland as well as the development of the prevalence, incidence,
      mortality and costs between 2006 and 2011. METHODS: Using health care claims data
      of a large health insurance group, current epidemiology and costs were determined
      from a sample of adult enrollees in 2011. The identification of patients with
      diabetes was based on prescription data of diabetes related drugs using the
      Anatomical Therapeutic Chemical Classification as proxy for clinical diagnosis.
      We further evaluated changes in epidemiology and costs between 2006 and 2011. All
      results were weighted with census data to achieve an extrapolation to the Swiss
      general population level. RESULTS: A total of 920'402 patients were enrolled in
      2011 and 49'757 (5.4%) were identified as diabetes cases. The extrapolated
      overall prevalence of diabetes in Switzerland was 4.9% (2006, 3.9%). The
      incidence was 0.58% in 2011 (2007, 0.63%). The extrapolated mortality rate was
      2.6% with no significant change over time. Annual diabetes costs to the mandatory
      health insurance increased from EUR 5,036 per patient in 2006 to EUR 5'331 per
      patient in 2011. CONCLUSIONS: This study shows a high medical and economic burden
      of diabetes. The prevalence and costs of diabetes in Switzerland increased
      substantially over time. Findings stress the need for public health strategies to
      manage patients with chronic conditions and optimize resource allocation in
      health service delivery systems.

PMID- 24894894
TI  - Echocardiographic measurements of cardiac dimensions correlate better with body
      length than with body weight or body surface area.
AB  - Looking after children means caring for very small infants up to adult-sized
      adolescents, with weights ranging from 500 g to more than 100 kg and heights
      ranging from 25 to more than 200 cm. The available echocardiographic reference
      data were drawn from a small sample, which did not include preterm infants. Most
      authors have used body weight or body surface area to predict left ventricular
      dimensions. The current authors had the impression that body length would be a
      better surrogate parameter than body weight or body surface area. They analyzed
      their echocardiographic database retrospectively. The analysis included all
      available echocardiographic data from 6 June 2001 to 15 December 2011 from their
      echocardiographic database. The authors included 12,086 of 26,325 subjects
      documented as patients with normal hearts in their analysis by the examining the
      pediatric cardiologist. For their analysis, they selected body weight, length,
      age, and aortic and pulmonary valve diameter in two-dimensional echocardiography
      and left ventricular dimension in M-mode. They found good correlation between
      echocardiographic dimensions and body surface area, body weight, and body length.
      The analysis showed a complex relationship between echocardiographic measurements
      and body weight and body surface area, whereas body length showed a linear
      relationship. This makes prediction of echo parameters more reliable. According
      to this retrospective analysis, body length is a better parameter for evaluating
      echocardiographic measurements than body weight or body surface area and should
      therefore be used in daily practice.

PMID- 24894890
TI  - Mechanisms of guided bone regeneration: a review.
AB  - Post-extraction crestal bone resorption is common and unavoidable which can lead
      to significant ridge dimensional changes. To regenerate enough bone for
      successful implant placement, Guided Bone Regeneration (GBR) is often required.
      GBR is a surgical procedure that uses barrier membranes with or without
      particulate bone grafts or/and bone substitutes. There are two approaches of GBR
      in implant therapy: GBR at implant placement (simultaneous approach) and GBR
      before implant placement to increase the alveolar ridge or improve ridge
      morphology (staged approach). Angiogenesis and ample blood supply play a critical
      role in promoting bone regeneration. 

PMID- 24894892
TI  - Clinical assessment of peripheral perfusion to predict postoperative
      complications after major abdominal surgery early: a prospective observational
      study in adults.
AB  - INTRODUCTION: Altered peripheral perfusion is strongly associated with poor
      outcome in critically ill patients. We wanted to determine whether repeated
      assessments of peripheral perfusion during the days following surgery could help
      to early identify patients that are more likely to develop postoperative
      complications. METHODS: Haemodynamic measurements and peripheral perfusion
      parameters were collected one day prior to surgery, directly after surgery (D0)
      and on the first (D1), second (D2) and third (D3) postoperative days. Peripheral
      perfusion assessment consisted of capillary refill time (CRT), peripheral
      perfusion index (PPI) and forearm-to-fingertip skin temperature gradient (T(skin
      diff)). Generalized linear mixed models were used to predict severe complications
      within ten days after surgery based on Clavien-Dindo classification. RESULTS: We
      prospectively followed 137 consecutive patients, from among whom 111 were
      included in the analysis. Severe complications were observed in 19 patients
      (17.0%). Postoperatively, peripheral perfusion parameters were significantly
      altered in patients who subsequently developed severe complications compared to
      those who did not, and these parameters persisted over time. CRT was altered at
      D0, and PPI and T(skin-diff) were altered on D1 and D2, respectively. Among the
      different peripheral perfusion parameters, the diagnostic accuracy in predicting
      severe postoperative complications was highest for CRT on D2 (area under the
      receiver operating characteristic curve = 0.91 (95% confidence interval (CI) =
      0.83 to 0.92)) with a sensitivity of 0.79 (95% CI = 0.54 to 0.94) and a
      specificity of 0.93 (95% CI = 0.86 to 0.97). Generalized mixed-model analysis
      demonstrated that abnormal peripheral perfusion on D2 and D3 was an independent
      predictor of severe postoperative complications (D2 odds ratio (OR) = 8.4, 95% CI
      = 2.7 to 25.9; D2 OR = 6.4, 95% CI = 2.1 to 19.6). CONCLUSIONS: In a group of
      patients assessed following major abdominal surgery, peripheral perfusion
      alterations were associated with the development of severe complications
      independently of systemic haemodynamics. Further research is needed to confirm
      these findings and to explore in more detail the effects of peripheral perfusion
      targeted resuscitation following major abdominal surgery.

PMID- 24894893
TI  - Splanchnic near-infrared spectroscopy and risk of necrotizing enterocolitis after
      neonatal heart surgery.
AB  - Infants with critical congenital heart disease, especially patients with a single
      ventricle (SV) physiology, are at increased risk for the development of
      necrotizing enterocolitis (NEC). Decreased splanchnic oxygen delivery may
      contribute to the development of NEC and may be detected by regional oximetry
      (rSO2) via splanchnic near-infrared spectroscopy (NIRS). This prospective study
      enrolled 64 neonates undergoing biventricular (BV) repair or SV palliation for
      CHD and monitored postoperative splanchnic rSO2 before and during initiation of
      enteral feedings to determine whether changes in rSO2 are associated with risk of
      NEC. Suspected or proven NEC was observed in 32 % (11/34) of the SV subjects and
      0 % (0/30) of the BV subjects (p = 0.001). Compared with the BV subjects, the SV
      palliated subjects had significantly lower splanchnic rSO2 before and during
      initiation of enteral feedings, but the groups showed no difference after
      correction for lower pulse oximetry (SpO2) in the SV group. The clinical
      parameters were similar among the SV subjects with and without NEC except for
      cardiopulmonary bypass times, which were longer for the patients who experienced
      NEC (126 vs 85 min; p = 0.03). No difference was observed in splanchnic rSO2 or
      in the SpO2-rSO2 difference between the SV subjects with and without NEC.
      Compared with the patients who had suspected or no NEC, the subjects with proven
      NEC had a lower average splanchnic rSO2 (32.6 vs 47.0 %; p = 0.05), more time
      with rSO2 less than 30 % (48.8 vs 6.7 %; p = 0.04) at one-fourth-volume feeds,
      and more time with SpO2-rSO2 exceeding 50 % (33.3 vs 0 %; p = 0.03) before feeds
      were initiated. These data suggest that splanchnic NIRS may be a useful tool for
      assessing risk of NEC, especially in patients with an SV physiology.

PMID- 24894895
TI  - Heart-rate-corrected QT interval evolution in premature infants during the first
      week of life.
AB  - Automated monitoring of the QT interval is increasingly common in a variety of
      clinical settings. A better understanding of how the heart-rate-corrected QT
      interval (QTc) evolves in early postnatal life is needed before its clinical
      utility in neonates can be determined. This study aimed to use real-time bedside
      monitoring as a tool to describe the QTc evolution of premature neonates during
      the first week of life. All neonates born at a gestation age (GA) of 31 weeks or
      later and admitted to the level 2 intensive care nursery of the authors'
      institution between December 2012 and March 2013 were included in this study. The
      authors prospectively collected QTc values at 15-min intervals during the first
      week of life, then used two-way analysis of variance (ANOVA) to compare these
      data among three GA cohorts: 31 to <34 weeks (cohort A), 34 to <37 weeks (cohort
      B), and >=37 weeks (cohort C). All the cohorts demonstrated a statistically
      significant decline in the 24-h average QTc during the first 3-4 days of life
      before reaching a stable baseline. No diurnal variation in the QTc was identified
      in any of the study patients. Marked variability and a progressive decline in the
      QTc of premature neonates occur during the first 3-4 days of life. Understanding
      this phenomenon is imperative when screening programs for the early detection of
      QT prolongation are considered.

PMID- 24894896
TI  - Surgical volume-to-outcome relationship and monitoring of technical performance
      in pediatric cardiac surgery.
AB  - A significant inverse relationship of surgical institutional and surgeon volumes
      to outcome has been demonstrated in many high-stakes surgical specialties. By and
      large, the same results were found in pediatric cardiac surgery, for which a more
      thorough analysis has shown that this relationship depends on case complexity and
      type of surgical procedures. Lower-volume programs tend to underperform larger
      volume programs as case complexity increases. High-volume pediatric cardiac
      surgeons also tend to have better results than low-volume surgeons, especially at
      the more complex end of the surgery spectrum (e.g., the Norwood procedure).
      Nevertheless, this trend for lower mortality rates at larger centers is not
      universal. All larger programs do not perform better than all smaller programs.
      Moreover, surgical volume seems to account for only a small proportion of the
      overall between-center variation in outcome. Intraoperative technical performance
      is one of the most important parts, if not the most important part, of the
      therapeutic process and a critical component of postoperative outcome. Thus, the
      use of center-specific, risk-adjusted outcome as a tool for quality assessment
      together with monitoring of technical performance using a specific score may be
      more reliable than relying on volume alone. However, the relationship between
      surgical volume and outcome in pediatric cardiac surgery is strong enough that it
      ought to support adapted and well-balanced health care strategies that take
      advantage of the positive influence that higher center and surgeon volumes have
      on outcome. 

PMID- 24894897
TI  - Admission to a dedicated cardiac intensive care unit is associated with decreased
      resource use for infants with prenatally diagnosed congenital heart disease.
AB  - Many factors in the delivery and perinatal care of infants with a prenatal
      diagnosis of congenital heart disease (CHD) have an impact on outcome and costs.
      This study sought to determine the modifiable factors in perinatal management
      that have an impact on postnatal resource use for infants with CHD. The medical
      records of infants with prenatally diagnosed CHD (August 2006-December 2011) who
      underwent cardiac surgery before discharge were reviewed. The exclusion criteria
      ruled out prematurity and intervention or transplantation evaluation before
      surgery. Clinical characteristics, outcomes, and cost data were collected.
      Multivariate linear regression models were used to determine the impact of
      perinatal decisions on hospitalization cost and surrogates of resource use after
      adjustment for demographic and other risk factors. For the 126 patients who met
      the study criteria, the median hospital stay was 22 days (range 4-122 days), and
      the median inflation-adjusted total hospital cost was $107,357 (range $9,746
      602,320). The initial admission to the neonatal versus the cardiac intensive care
      unit (NICU vs. CICU) was independently associated with a 19 % longer hospital
      stay, a 26 % longer ICU stay, and 47 % more mechanical ventilation days after
      adjustment for Risk Adjustment for Congenital Heart Surgery, version 1 score,
      gestation age, genetic abnormality, birth weight, mode of delivery, and
      postsurgical complications. Weekend versus weekday delivery was not associated
      with hospital cost or length of hospital stay. For term infants with prenatally
      diagnosed CHD undergoing surgery before discharge, preoperative admission to the
      NICU (vs. the CICU) resulted in a longer hospital stay and greater intensive care
      use. Prenatal planning for infants with CHD should consider the initial place of
      admission as a modifiable factor for potential lowering of resource use.

PMID- 24894898
TI  - Cyclooxygenase inhibitors in preterm infants with patent ductus arteriosus:
      effects on cardiac and vascular indices.
AB  - Existing data suggest subendocardial ischemia in preterm infants with patent
      ductus arteriosus (PDA) and alterations in cardiac function after indomethacin
      administration. This study aimed to explore the evolution of left ventricular
      function by conventional echocardiography and speckle-tracking echocardiography
      (STE) and to ascertain the interrelationship with coronary flow indices in
      response to indomethacin. A prospective observational study was performed with
      preterm infants receiving indomethacin for medical closure of PDA. Serial
      echocardiography was performed, and the results were analyzed using analysis of
      variance. Intra- and interobserver variability was assessed using the intraclass
      correlation coefficient. Indomethacin was administered to 18 infants born at a
      median gestational age of 25.8 weeks (interquartile range [IQR], 24.2-28.1 weeks)
      with a birth weight of 773 g (IQR, 704-1,002 g). The median age of the infants
      was 7.5 days (IQR, 4-17). Global longitudinal strain (GLS) values significantly
      decreased immediately after indomethacin infusion (preindomethacin GLS, -19.1 +/-
      2.4 % vs. -15.9 +/- 1.7 %; p < 0.0001) but had improved at reassessment after 1 h
      (-17.4 +/- 1.8 %). Conventional echocardiographic indices did not show
      significant alterations. A significant increase in arterial resistance in the
      coronary vasculature from 1.7 to 2.4 mmHg/cm/s was demonstrated. A significant
      correlation was noted between peak systolic GLS and flow resistance in the
      coronary vasculature. Significant changes in myocardial indices were observed
      immediately after indomethacin infusion. Compared with conventional methods, STE
      is a more sensitive tool to facilitate understanding of hemodynamics in preterm
      infants.

PMID- 24894899
TI  - Different rates of DNA replication at early versus late S-phase sections:
      multiscale modeling of stochastic events related to DNA content/EdU (5-ethynyl
      2'deoxyuridine) incorporation distributions.
AB  - Mathematical modeling allows relating molecular events to single-cell
      characteristics assessed by multiparameter cytometry. In the present study we
      labeled newly synthesized DNA in A549 human lung carcinoma cells with 15-120 min
      pulses of EdU. All DNA was stained with DAPI and cellular fluorescence was
      measured by laser scanning cytometry. The frequency of cells in the ascending
      (left) side of the "horseshoe"-shaped EdU/DAPI bivariate distributions reports
      the rate of DNA replication at the time of entrance to S phase while their
      frequency in the descending (right) side is a marker of DNA replication rate at
      the time of transition from S to G2 phase. To understand the connection between
      molecular-scale events and scatterplot asymmetry, we developed a multiscale
      stochastic model, which simulates DNA replication and cell cycle progression of
      individual cells and produces in silico EdU/DAPI scatterplots. For each S-phase
      cell the time points at which replication origins are fired are modeled by a non
      homogeneous Poisson Process (NHPP). Shifted gamma distributions are assumed for
      durations of cell cycle phases (G1, S and G2 M), Depending on the rate of DNA
      synthesis being an increasing or decreasing function, simulated EdU/DAPI
      bivariate graphs show predominance of cells in left (early-S) or right (late-S)
      side of the horseshoe distribution. Assuming NHPP rate estimated from independent
      experiments, simulated EdU/DAPI graphs are nearly indistinguishable from those
      experimentally observed. This finding proves consistency between the S-phase DNA
      replication rate based on molecular-scale analyses, and cell population kinetics
      ascertained from EdU/DAPI scatterplots and demonstrates that DNA replication rate
      at entrance to S is relatively slow compared with its rather abrupt termination
      during S to G2 transition. Our approach opens a possibility of similar modeling
      to study the effect of anticancer drugs on DNA replication/cell cycle progression
      and also to quantify other kinetic events that can be measured during S-phase.

PMID- 24894900
TI  - In vitro synthesis of the E. coli Sec translocon from DNA.
AB  - Difficulties in constructing complex lipid/protein membranes have severely
      limited the development of functional artificial cells endowed with vital
      membrane-related functions. The Sec translocon membrane channel, which mediates
      the insertion of membrane proteins into the plasma membrane, was constructed in
      the membrane of lipid vesicles through in vitro expression of its component
      proteins. The components of the Sec translocon were synthesized from their
      respective genes in the presence of liposomes, thereby bringing about a
      functional complex. The synthesized E. coli Sec translocon mediated the membrane
      translocation of single- and multi-span membrane proteins. The successful
      translocation of a functional peptidase into the liposome lumen further confirmed
      the proper insertion of the translocon complex. Our results demonstrate the
      feasible construction of artificial cells, the membranes of which can be
      functionalized by directly decoding genetic information into membrane functions. 

PMID- 24894901
TI  - Zn vacancy induced green luminescence on non-polar surfaces in ZnO
      nanostructures.
AB  - Although generally ascribed to the presence of defects, an ultimate assignment of
      the different contributions to the emission spectrum in terms of surface states
      and deep levels in ZnO nanostructures is still lacking. In this work we
      unambiguously give first evidence that zinc vacancies at the (1010) nonpolar
      surfaces are responsible for the green luminescence of ZnO nanostructures. The
      result is obtained by performing an exhaustive comparison between spatially
      resolved cathodoluminescence spectroscopy and imaging and ab initio simulations.
      Our findings are crucial to control undesired recombinations in nanostructured
      devices. 

PMID- 24894902
TI  - Presence of OXA-type enzymes in Achromobacter insuavis and A. dolens.
AB  - The accurate species identification of Achromobacter isolates is difficult and
      the clinical isolates of this genus are mostly referred as A. xylosoxidans. Here,
      we report new OXA variants in 2 isolates identified as A. insuavis (A114, A79)
      and 1 isolate identified as A. dolens (A336). These results suggest that
      different bla OXA genes are ubiquitous in the different species of Achromobacter
      spp. The role of the other species of Achromobacter in clinical samples needs to
      be reevaluated, and the proper identification is absolutely necessary to
      understand the epidemiology of this genus. 

PMID- 24894903
TI  - Sequence polymorphism of GroEL gene in natural population of Bacillus and
      Brevibacillus spp. that showed variation in thermal tolerance capacity and mRNA
      expression.
AB  - GroEL, a class I chaperonin, plays an important role in the thermal adaptation of
      the cell and helps to maintain the viability of the cell under heat shock
      condition. Function of groEL in vivo depends on the maintenance of proper
      structure of the protein which in turn depends on the nucleotide and amino acid
      sequence of the gene. In this study, we investigated the changes in nucleotide
      and amino acid sequences of the partial groEL gene that may affect the
      thermotolerance capacity as well as mRNA expression of bacterial isolates.
      Sequences among the same species having differences in the amino acid level were
      identified as different alleles. The effect of allelic variation on the groEL
      gene expression was analyzed by comparison and relative quantification in each
      allele under thermal shock condition by RT-PCR. Evaluation of K a/K s ratio among
      the strains of same species showed that the groEL gene of all the species had
      undergone similar functional constrain during evolution. The strains showing
      similar thermotolerance capacity was found to carry same allele of groEL gene.
      The isolates carrying allele having amino acid substitution inside the highly
      ATP/ADP or Mg(2+)-binding region could not tolerate thermal stress and showed
      lower expression of the groEL gene. Our results indicate that during evolution of
      these bacterial species the groEL gene has undergone the process of natural
      selection, and the isolates have evolved with the groEL allelic sequences that
      help them to withstand the thermal stress during their interaction with the
      environment. 

PMID- 24894904
TI  - Screening for differentially expressed genes in endophytic fungus strain 39
      during co-culture with herbal extract of its host Dioscorea nipponica Makino.
AB  - Strain 39 is an endophytic fungus which was isolated from Dioscorea nipponica
      Makino (DNM). After Strain 39 co-cultured with ethanol extract of DNM rhizomes
      for several days, the content of saponins in this culture mixture would be
      obviously increased. To analyze the mechanism of this microbial transformation,
      we used the differential display reverse transcription polymerase chain reaction
      (DDRT-PCR) method to compare the transcriptomes between Strain 39 cultured in
      normal PD medium and in PD medium which added ethanol extract of DNM rhizomes. We
      amplified 29 DDRT-PCR bands using 12 primer combinations of three anchored
      primers and five random primers, and six bands were re-amplified. Analysis of
      real-time PCR and sequence alignment showed that three clones were up-regulated
      in sample group: squalene epoxidase, squalene synthase, and catalase, one clone
      was expressed only in sample group. The possible roles and origins of the above
      genes were discussed, and the molecular mechanism of Strain 39 biotransformation
      was speculated. This study is the first report of the molecular biotransformation
      mechanism of saponins production by endophytic fungus of DNM. 

PMID- 24894905
TI  - Cohnella humi sp. nov., isolated from Russian soil.
AB  - A Gram-positive, catalase and oxidase positive, rod-shaped bacteria, and spore
      forming, designated as J20-3(T) was isolated from a peat soil, collected near a
      coal mine at Prokopyevsk, (GPS; N53 degrees 52'51", E86 degrees 43'39") Kemerovo
      Oblast, Russia. A polyphasic taxonomy study using phenotypic, phylogenetic, and
      genotypic method was performed to characterize strain J20-3(T). Comparative 16S
      rRNA gene sequence analysis indicated that strain J20-3(T) represented a novel
      subline within the genus Cohnella in the family Paenibacillaceae. According to
      16S rRNA gene sequence, strain J20-3(T) showed 93.7-97.2 % similarity levels with
      other Cohnella species. Strain J20-3(T) exhibited relatively low level of DNA-DNA
      hybridization value with type strains KACC 11643(T) (40 %), KACC 11771(T) (37.5
      %), and KACC 15372(T) (30.5 %). The strain showed typical chemotaxonomic
      characteristic of the genus Cohnella, with the presence of predominant
      respiratory quinone MK-7; major fatty acids are C15:0, C16:0, iso, and C16:0. The
      DNA G+C content of the strain J20-3(T) was 56.3 mol%. The polar lipid profile of
      the strain J20-3(T) included major amount of diphosphatidylglycerol,
      phosphatidylglycerol, and phosphoatidylethanolamine. On the basis of its
      phenotypic and genotypic properties, and its phylogenetic distinctiveness, strain
      J20-3(T) should be classified as a novel species in the genus Cohnella, for which
      the name Cohnella humi sp. nov. is proposed. 

PMID- 24894906
TI  - Detection of Nosema bombycis by FTA cards and loop-mediated isothermal
      amplification (LAMP).
AB  - We successfully established a detection method which exhibited a markedly higher
      sensitivity than previously developed detection methods for Nosema bombycis by
      combining glass beads, FTA card, and LAMP. Spores of N. bombycis were first
      broken by acid-washed glass beads; the DNA was subsequently extracted and
      purified with the FTA card, and LAMP was performed using primers (LSU296)
      designed based on the sequence of the LSU rRNA of N. bombycis. The minimum
      detection concentration was 10 spores/mL. When this method was used to detect
      pebrine disease in silkworm egg, the detection rate for 500 silkworm eggs, in
      which only one egg was infected with N. bombycis, was 100 % under our optimized
      conditions. If the number of eggs in the sample increased to 800 or 1,000, the
      sample was divided into two equal portions, and the eggs were smashed with glass
      beads after the addition of 1 mL of TE buffer. The liquid in two tubes was later
      mixed and applied to the FTA card, and the detection rates were 100 %.
      Furthermore, the LAMP method established in our study could detect N. bombycis
      infection in silkworm 24 h earlier than microscopy. 

PMID- 24894909
TI  - Large scale molecular simulations of nanotoxicity.
AB  - The widespread use of nanomaterials in biomedical applications has been
      accompanied by an increasing interest in understanding their interactions with
      tissues, cells, and biomolecules, and in particular, on how they might affect the
      integrity of cell membranes and proteins. In this mini-review, we present a
      summary of some of the recent studies on this important subject, especially from
      the point of view of large scale molecular simulations. The carbon-based
      nanomaterials and noble metal nanoparticles are the main focus, with additional
      discussions on quantum dots and other nanoparticles as well. The driving forces
      for adsorption of fullerenes, carbon nanotubes, and graphene nanosheets onto
      proteins or cell membranes are found to be mainly hydrophobic interactions and
      the so-called pi-pi stacking (between aromatic rings), while for the noble metal
      nanoparticles the long-range electrostatic interactions play a bigger role. More
      interestingly, there are also growing evidences showing that nanotoxicity can
      have implications in de novo design of nanomedicine. For example, the endohedral
      metallofullerenol Gd@C82(OH)22 is shown to inhibit tumor growth and metastasis by
      inhibiting enzyme MMP-9, and graphene is illustrated to disrupt bacteria cell
      membranes by insertion/cutting as well as destructive extraction of lipid
      molecules. These recent findings have provided a better understanding of
      nanotoxicity at the molecular level and also suggested therapeutic potential by
      using the cytotoxicity of nanoparticles against cancer or bacteria cells.

PMID- 24894907
TI  - The effect of tunicamycin on the glucose uptake, growth, and cellular adhesion in
      the protozoan parasite Crithidia fasciculata.
AB  - Crithidia fasciculata represents a very interesting model organism to study
      biochemical, cellular, and genetic processes unique to members of the family of
      the Trypanosomatidae. Thus, C. fasciculata parasitizes several species of insects
      and has been widely used to test new therapeutic strategies against parasitic
      infections. By using tunicamycin, a potent inhibitor of glycosylation in
      asparaginyl residues of glycoproteins (N-glycosylation), we demonstrate that N
      glycosylation in C. fasciculata cells is involved in modulating glucose uptake,
      dramatically impacting growth, and cell adhesion. C. fasciculata treated with
      tunicamycin was severely affected in their ability to replicate and to adhere to
      polystyrene substrates and losing their ability to aggregate into small and large
      groups. Moreover, under tunicamycin treatment, the parasites were considerably
      shorter and rounder and displayed alterations in cytoplasmic vesicles formation.
      Furthermore, glucose uptake was significantly impaired in a tunicamycin dose
      dependent manner; however, no cytotoxic effect was observed. Interestingly, this
      effect was reversible. Thus, when tunicamycin was removed from the culture media,
      the parasites recovered its growth rate, cell adhesion properties, and glucose
      uptake. Collectively, these results suggest that changes in the tunicamycin
      dependent glycosylation levels can influence glucose uptake, cell growth, and
      adhesion in the protozoan parasite C. fasciculata. 

PMID- 24894908
TI  - Metabolic syndrome: is equine disease comparable to what we know in humans?
AB  - This review summarizes similarities and differences between the metabolic
      syndromes in humans and equines, concerning the anatomy, symptoms, and
      pathophysiological mechanisms. In particular, it discusses the structure and
      distribution of adipose tissue and its specific metabolic pathways. Furthermore,
      this article provides insights and focuses on issues concerning laminitis in
      horses and cardiovascular diseases in humans, as well as their overlap. 

PMID- 24894910
TI  - Removing arsenic from groundwater in Cambodia using high performance iron
      adsorbent.
AB  - In Cambodia, groundwater has been contaminated with arsenic, and purification of
      the water is an urgent issue. From 2010 to 2012, an international collaborative
      project between Japan and Cambodia for developing arsenic-removing technology
      from well water was conducted and supported by the foundation of New Energy and
      Industrial Technology Development Organization, Japan. Quality of well water was
      surveyed in Kandal, Prey Veng, and Kampong Cham Provinces, and a monitoring trial
      of the arsenic removal equipment using our patented amorphous iron (hydr)oxide
      adsorbent was performed. Of the 37 wells surveyed, arsenic concentration of 24
      exceeded the Cambodian guideline value (50 MUg L(-1)), and those of 27 exceeded
      the WHO guideline for drinking water (10 MUg L(-1)). Levels of arsenic were
      extremely high in some wells (>1,000-6,000 MUg L(-1)), suggesting that arsenic
      pollution of groundwater is serious in these areas. Based on the survey results,
      16 arsenic removal equipments were installed in six schools, three temples, two
      health centers, four private houses, and one commune office. Over 10 months of
      monitoring, the average arsenic concentrations of the treated water were between
      0 and 10 MUg L(-1) at four locations, 10-50 MUg L(-1) at eight locations, and >50
      MUg L(-1) at four locations. The arsenic removal rate ranged in 83.1-99.7%, with
      an average of 93.8%, indicating that the arsenic removal equipment greatly lower
      the risk of arsenic exposure to the residents. Results of the field trial showed
      that As concentration of the treated water could be reduced to <10 ug L(-1) by
      managing the As removal equipment properly, suggesting that the amorphous iron
      (hydr)oxide adsorbent has high adsorbing capacity for As not only in the
      laboratory environment but also in the field condition. This is one of the
      succeeding As removal techniques that could reduce As concentration of water
      below the WHO guideline value for As in situ.

PMID- 24894911
TI  - Biogeochemical indicators of elevated nitrogen deposition in semiarid
      Mediterranean ecosystems.
AB  - Nitrogen (N) deposition has doubled the natural N inputs received by ecosystems
      through biological N fixation and is currently a global problem that is affecting
      the Mediterranean regions. We evaluated the existing relationships between
      increased atmospheric N deposition and biogeochemical indicators related to soil
      chemical factors and cryptogam species across semiarid central, southern, and
      eastern Spain. The cryptogam species studied were the biocrust-forming species
      Pleurochaete squarrosa (moss) and Cladonia foliacea (lichen). Sampling sites were
      chosen in Quercus coccifera (kermes oak) shrublands and Pinus halepensis (Aleppo
      pine) forests to cover a range of inorganic N deposition representative of the
      levels found in the Iberian Peninsula (between 4.4 and 8.1 kg N ha(-1) year(-1)).
      We extended the ambient N deposition gradient by including experimental plots to
      which N had been added for 3 years at rates of 10, 20, and 50 kg N ha(-1) year(
      1). Overall, N deposition (extant plus simulated) increased soil inorganic N
      availability and caused soil acidification. Nitrogen deposition increased
      phosphomonoesterase (PME) enzyme activity and PME/nitrate reductase (NR) ratio in
      both species, whereas the NR activity was reduced only in the moss. Responses of
      PME and NR activities were attributed to an induced N to phosphorus imbalance and
      to N saturation, respectively. When only considering the ambient N deposition,
      soil organic C and N contents were positively related to N deposition, a response
      driven by pine forests. The PME/NR ratios of the moss were better predictors of N
      deposition rates than PME or NR activities alone in shrublands, whereas no
      correlation between N deposition and the lichen physiology was observed. We
      conclude that integrative physiological measurements, such as PME/NR ratios,
      measured on sensitive species such as P. squarrosa, can provide useful data for
      national-scale biomonitoring programs, whereas soil acidification and soil C and
      N storage could be useful as additional corroborating ecosystem indicators of
      chronic N pollution.

PMID- 24894912
TI  - beta1-Adrenoceptor autoantibodies affect action potential duration and delayed
      rectifier potassium currents in guinea pigs.
AB  - beta1-Adrenoceptor autoantibodies (beta1-AAs) affect the action potential
      duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The
      delayed rectifier potassium current (I K) plays a crucial role in APD, but the
      effects of beta1-AAs on I K have not been completely illuminated. This work aimed
      to observe the effects of beta1-AAs on I K and APD and further explore the
      mechanisms of beta1-AA-mediated ventricular arrhythmias. beta1-AAs were obtained
      from sera of patients with coronary heart disease (CHD) and nonsustained
      ventricular tachycardia. With whole-cell patch clamp technique, action potentials
      and I K were recorded. The results illustrated 0.1 MUmol/L beta1-AAs shortened
      APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01
      MUmol/L, beta1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001
      MUmol/L, beta1-AAs significantly prolonged APD90 and APD50. Moreover, beta1-AAs
      (0.001, 0.01, 0.1 MUmol/L) dose-dependently increased the rapidly activating
      delayed rectifier potassium current (I Kr), but similarly decreased the slowly
      activating delayed rectifier potassium current (I Ks) and increased L-type
      calcium currents at the different concentrations. Taken together, the IKr
      increase induced by high beta1-AA concentrations is responsible for a significant
      APD reduction which would contribute to repolarization changes and trigger the
      malignant ventricular arrhythmias in CHD patients.

PMID- 24894913
TI  - Neuropeptides: metabolism to bioactive fragments and the pharmacology of their
      receptors.
AB  - The proteolytic processing of neuropeptides has an important regulatory function
      and the peptide fragments resulting from the enzymatic degradation often exert
      essential physiological roles. The proteolytic processing generates, not only
      biologically inactive fragments, but also bioactive fragments that modulate or
      even counteract the response of their parent peptides. Frequently, these peptide
      fragments interact with receptors that are not recognized by the parent peptides.
      This review discusses tachykinins, opioid peptides, angiotensins, bradykinins,
      and neuropeptide Y that are present in the central nervous system and their
      processing to bioactive degradation products. These well-known neuropeptide
      systems have been selected since they provide illustrative examples that
      proteolytic degradation of parent peptides can lead to bioactive metabolites with
      different biological activities as compared to their parent peptides. For
      example, substance P, dynorphin A, angiotensin I and II, bradykinin, and
      neuropeptide Y are all degraded to bioactive fragments with pharmacological
      profiles that differ considerably from those of the parent peptides. The review
      discusses a selection of the large number of drug-like molecules that act as
      agonists or antagonists at receptors of neuropeptides. It focuses in particular
      on the efforts to identify selective drug-like agonists and antagonists mimicking
      the effects of the endogenous peptide fragments formed. As exemplified in this
      review, many common neuropeptides are degraded to a variety of smaller fragments
      but many of the fragments generated have not yet been examined in detail with
      regard to their potential biological activities. Since these bioactive fragments
      contain a small number of amino acid residues, they provide an ideal starting
      point for the development of drug-like substances with ability to mimic the
      effects of the degradation products. Thus, these substances could provide a rich
      source of new pharmaceuticals. However, as discussed herein relatively few
      examples have so far been disclosed of successful attempts to create
      bioavailable, drug-like agonists or antagonists, starting from the structure of
      endogenous peptide fragments and applying procedures relying on stepwise
      manipulations and simplifications of the peptide structures. 

PMID- 24894915
TI  - Complementary substrate-selectivity of metabolic adaptive convergence in the
      lignocellulolytic performance by Dichomitus squalens.
AB  - The lignocellulolytic platform of the wood-decaying organism Dichomitus squalens
      is important for production of biodegradable elements; however, the system has
      not yet been fully characterized. In this study, using statistical target
      optimization, we analysed substrate selectivity based on a variety of D. squalens
      metabolic pathways using combined omics tools. As compared with the alkali-lignin
      (AL) programme, the rice straw (RS) programme has the advantage of multilayered
      signalling to regulate cellulolytic-related genes or to connect their pathways.
      The spontaneous instability of the AL programme was accelerated by harsh
      starvation as compared with that of the RS programme. Therefore, the AL programme
      converged on cellular maintenance much easier and more rapidly. However,
      regardless of external substrate/concentration type, the compensatory pattern of
      the major targets (especially peroxidases and growth regulators) was similar,
      functioning to maintain cellular homeostasis. Interestingly, ligninolytic
      mediated targets under non-kaleidoscopic conditions were induced by a substrate
      input-control, and especially this mechanism had an important effect on the early
      stages of the biodegradation process. This optimized target analysis could be
      used to understand lignocellulolytic network and to improve downstream
      efficiency. 

PMID- 24894917
TI  - Terms of the debate on the format and structure of visual memory.
AB  - Our ability to actively maintain information in visual memory is strikingly
      limited. There is considerable debate about why this is so. As with many
      questions in psychology, the debate is framed dichotomously: Is visual working
      memory limited because it is supported by only a small handful of discrete
      "slots" into which visual representations are placed, or is it because there is
      an insufficient supply of a "resource" that is flexibly shared among visual
      representations? Here, we argue that this dichotomous framing obscures a set of
      at least eight underlying questions. Separately considering each question reveals
      a rich hypothesis space that will be useful for building a comprehensive model of
      visual working memory. The questions regard (1) an upper limit on the number of
      represented items, (2) the quantization of the memory commodity, (3) the
      relationship between how many items are stored and how well they are stored, (4)
      whether the number of stored items completely determines the fidelity of a
      representation (vs. fidelity being stochastic or variable), (5) the flexibility
      with which the memory commodity can be assigned or reassigned to items, (6) the
      format of the memory representation, (7) how working memories are formed, and (8)
      how memory representations are used to make responses in behavioral tasks. We
      reframe the debate in terms of these eight underlying questions, placing slot and
      resource models as poles in a more expansive theoretical space. 

PMID- 24894916
TI  - Exploring the multidimensionality of stature variation in the past through
      comparisons of archaeological and living populations.
AB  - Adult stature variation is commonly attributed to differential stress-levels
      during development. However, due to selective mortality and heterogeneous
      frailty, a population's tall stature may be more indicative of high selective
      pressures than of positive life conditions. This article examines stature in a
      biocultural context and draws parallels between bioarchaeological and living
      populations to explore the multidimensionality of stature variation in the past.
      This study investigates: 1) stature differences between archaeological
      populations exposed to low or high stress (inferred from skeletal indicators); 2)
      similarities in growth retardation patterns between archaeological and living
      groups; and 3) the apportionment of variance in growth outcomes at the regional
      level in archaeological and living populations. Anatomical stature estimates were
      examined in relation to skeletal stress indicators (cribra orbitalia, porotic
      hyperostosis, linear enamel hypoplasia) in two medieval bioarchaeological
      populations. Stature and biocultural information were gathered for comparative
      living samples from South America. Results indicate 1) significant (P < 0.01)
      differences in stature between groups exposed to different levels of skeletal
      stress; 2) greater prevalence of stunting among living groups, with similar
      patterns in socially stratified archaeological and modern groups; and 3) a degree
      of regional variance in growth outcomes consistent with that observed for highly
      selected traits. The relationship between early stress and growth is confounded
      by several factors-including catch-up growth, cultural buffering, and social
      inequality. The interpretations of early life conditions based on the
      relationship between stress and stature should be advanced with caution.

PMID- 24894918
TI  - Solitary Peutz-Jeghers polyp presenting as duodenal intussusception.

PMID- 24894914
TI  - Genes and signaling pathways involved in memory enhancement in mutant mice.
AB  - Mutant mice have been used successfully as a tool for investigating the
      mechanisms of memory at multiple levels, from genes to behavior. In most cases,
      manipulating a gene expressed in the brain impairs cognitive functions such as
      memory and their underlying cellular mechanisms, including synaptic plasticity.
      However, a remarkable number of mutations have been shown to enhance memory in
      mice. Understanding how to improve a system provides valuable insights into how
      the system works under normal conditions, because this involves understanding
      what the crucial components are. Therefore, more can be learned about the basic
      mechanisms of memory by studying mutant mice with enhanced memory. This review
      will summarize the genes and signaling pathways that are altered in the mutants
      with enhanced memory, as well as their roles in synaptic plasticity. Finally, I
      will discuss how knowledge of memory-enhancing mechanisms could be used to
      develop treatments for cognitive disorders associated with impaired plasticity. 

PMID- 24894919
TI  - Both retention and recirculation contribute to long-lived regulatory T-cell
      accumulation in the thymus.
AB  - Natural Treg cells acquire their lineage-determining transcription factor Foxp3
      during development in the thymus and are important in maintaining immunologic
      tolerance. Here, we analyzed the composition of the thymic Treg-cell pool using
      RAG2-GFP/FoxP3-RFP dual reporter mice and found that a population of long-lived
      GFP(-) Treg cells exists in the thymus. These long-lived Treg cells substantially
      increased with age, to a point where they represent >90% of the total thymic Treg
      cell pool at 6 months of age. In contrast, long-lived conventional T cells
      remained at ~ 15% of the total thymic pool at 6 months of age. Consistent with
      these studies, we noticed that host-derived Treg cells represented a large
      fraction (~ 10%) of the total thymic Treg-cell pool in bone marrow chimeras,
      suggesting that long-lived Treg cells also reside in the thymus of these mice.
      The pool of long-lived Treg cells in the thymus was sustained by retention of
      Treg cells in the thymus and by recirculation of peripheral Treg cells back into
      the thymus. These long-lived thymic Treg cells suppressed T-cell proliferation to
      an equivalent extent to splenic Treg cells. Together, these data demonstrate that
      long-lived Treg cells accumulate in the thymus by both retention and
      recirculation.

PMID- 24894921
TI  - Combination of intra-arterial therapies and sorafenib: is there a clinical
      benefit?
AB  - Intra-arterial therapies (IATs) play a major role in the treatment of patients
      with unresectable hepatocellular carcinoma. Over the last three decades, multiple
      loco-regional approaches such as transarterial chemoembolization or
      radioembolization were shown to effectively achieve local tumor control, offering
      significant survival benefits for selected patients with intermediate to advanced
      stage disease (Barcelona Clinic Liver Cancer stage B and C). These therapies
      provide a dual benefit of safely delivering a highly cytotoxic payload directly
      to the tumor while reducing systemic toxicity. This capability maintained the
      advantage of IATs over conventional systemic chemotherapy. The introduction of
      sorafenib as a systemically applicable drug, the first of its kind to provide
      survival benefits by means of oral monotherapy, contributed to a paradigm change.
      The idea of combining this novel agent with IATs seemed intriguing, and a variety
      of national and international clinical trials were initiated to explore the
      potential benefits of this exciting new option. A plethora of preliminary data
      has been made available throughout the last 5 years, and the interpretation of
      the inhomogeneously designed protocols proved difficult. In this review, we will
      provide a brief state-of-the-art update on the most frequently used intra
      arterial modalities and discuss the molecular mechanism, potential biomarkers as
      well as the safety profile of sorafenib. Furthermore, we will discuss the role of
      the sequence of administration in combined therapies. Finally, this review will
      examine the evidence for clinical outcomes for the combination of different IATs
      with sorafenib.

PMID- 24894922
TI  - Critical role of HIFU in musculoskeletal interventions.
AB  - Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a totally
      noninvasive ablation technique that in the last years had an important
      development in a large number of applications: in particular gynaecological
      disorders, bone lesions, prostate, breast, brain and other organs. This review of
      MRgFUS is focused on the technical aspects and the current clinical application
      in musculoskeletal interventions. More precisely, this paper aims to review the
      relatively scarce literature on this topic also in comparison with our 3-year
      experience in the use of this technique in the field of musculoskeletal
      interventions. 

PMID- 24894925
TI  - Idiopathic intracranial hypertension associated with polycystic ovarian syndrome.
AB  - Idiopathic intracranial hypertension is defined as increased intracranial
      pressure of unknown origin. Idiopathic intracranial hypertension associated with
      polycystic ovarian syndrome (PCOS) is a rare condition in adolescence. We report
      the case of a 14-year-old girl with sudden onset of decreased visual acuity,
      headache and menstrual irregularity. Clinical neurological examination and
      magnetic resonance imaging of the brain and orbit were normal. Lumbar puncture
      demonstrated an increased opening pressure of 31 cm H2O. Gynecologic
      investigation indicated PCOS. Her symptoms improved with medical and surgical
      treatment for the underlying PCOS.

PMID- 24894923
TI  - Thermal ablation of liver metastases from colorectal cancer: radiofrequency,
      microwave and laser ablation therapies.
AB  - Surgery is currently considered the treatment of choice for patients with
      colorectal cancer liver metastases (CRLM) when resectable. The majority of these
      patients can also benefit from systemic chemotherapy. Recently, local or regional
      therapies such as thermal ablations have been used with acceptable outcomes. We
      searched the medical literature to identify studies and reviews relevant to
      radiofrequency (RF) ablation, microwave (MW) ablation and laser-induced
      thermotherapy (LITT) in terms of local progression, survival indexes and major
      complications in patients with CRLM. Reviewed literature showed a local
      progression rate between 2.8 and 29.7 % of RF-ablated liver lesions at 12-49
      months follow-up, 2.7-12.5 % of MW ablated lesions at 5-19 months follow-up and
      5.2 % of lesions treated with LITT at 6-month follow-up. Major complications were
      observed in 4-33 % of patients treated with RF ablation, 0-19 % of patients
      treated with MW ablation and 0.1-3.5 % of lesions treated with LITT. Although not
      significantly different, the mean of 1-, 3- and 5-year survival rates for RF-, MW
      and laser ablated lesions was (92.6, 44.7, 31.1 %), (79, 38.6, 21 %) and (94.2,
      61.5, 29.2 %), respectively. The median survival in these methods was 33.2, 29.5
      and 33.7 months, respectively. Thermal ablation may be an appropriate alternative
      in patients with CRLM who have inoperable liver lesions or have operable lesions
      as an adjunct to resection. However, further competitive evaluation should
      clarify the efficacy and priority of these therapies in patients with colorectal
      cancer liver metastases.

PMID- 24894926
TI  - Pediatric Hashimoto's encephalopathy with peripheral nervous system involvement.
AB  - Hashimoto encephalopathy is a syndrome of encephalopathy associated with elevated
      concentration of circulating serum anti-thyroid antibodies usually responsive to
      steroid therapy. We report a 13-year-old girl with Hashimoto encephalopathy and
      peripheral nervous system involvement. The child had experienced high-grade
      pyrexia, global headache and sleeplessness. After admission she had an ileus with
      a distended urinary bladder, hallucinations and cognitive impairment. She had
      reduced deep tendon reflexes and distal sensory deficiency. Anti-thyroglobulin
      antibodies were raised at 2121 IU/mL (normal, 0-40) and the anti-thyroperoxidase
      was high at 886 IU/mL (normal, 0-50). Progressive neurological and psychiatric
      remission was noted after i.v. methylprednisolone. Follow-up magnetic resonance
      imaging showed complete resolution of the foci of signal abnormality previously
      yielded. This case report is the first, to the best of our knowledge, to describe
      peripheral nervous system involvement in a child with a diagnosis of Hashimoto's
      encephalopathy.

PMID- 24894927
TI  - Eosinophilic granuloma of the sternum in a child treated with closed biopsy.
AB  - Langerhans cell histiocytosis is a rare neoplastic proliferative disorder of the
      Langerhans cells. The clinical course is variable, ranging from a low symptomatic
      single bone lesion to fatal multiple organ involvement. Rarely, the sternum can
      be the first and single location of the disease. We report on a 12-year-old boy
      who presented with an aggressive lytic lesion of the proximal sternum associated
      with local pain and afternoon fever. Histopathological analysis of the closed
      biopsy specimen indicated eosinophilic granuloma of bone/Langerhans cell
      histiocytosis. Soon after the biopsy procedure the pain and fever subsided.
      Computed tomography at 2 months showed healing of the lytic lesion. The patient
      received no other type of treatment. At 2 year follow up he was symptom and
      disease free. 

PMID- 24894924
TI  - Percutaneous bone lesion ablation.
AB  - Benign tumors and metastatic bone lesions can be treated by ablation techniques
      performed either alone or in combination with other percutaneous techniques.
      Ablation techniques include ethanol or acetic acid injection and thermal ablation
      by means of energy deposition [including laser, radiofrequency, microwave,
      cryoablation, radiofrequency ionization and magnetic resonance (MR)-guided high
      intensity focused ultrasound (HIFU)]. Goal definition of the therapy is crucial:
      ablation techniques can be proposed as curative treatments in benign bone tumors
      or oligometastatic disease (<3 lesions). Alternatively, these techniques can be
      proposed as palliative treatments aiming at reduction of pain, local control of
      the disease and tumor decompression. Depending on the lesion's location ablation
      can be combined with cementation with or without further metallic augmentation;
      local tumor control can be enhanced by combining ablation with transarterial
      bland embolization or chemoembolization. Thermal ablation of bone and soft
      tissues is characterized by high success and relatively low rates of potential
      complications, mainly iatrogenic thermal damage of surrounding sensitive
      structures. Successful thermal ablation requires a sufficient ablation volume and
      thermal protection of the surrounding vulnerable structures. This article will
      describe the general principles governing ablation and the mechanism of action
      for each technique and in addition will review the literature about safety and
      effectiveness of percutaneous imaging-guided ablation for benign and malignant
      (primary and metastatic) lesions. 

PMID- 24894928
TI  - Extraordinary cause of complete colonic obstruction in children: urinary
      retention.
AB  - Complete colonic obstruction in children may occur secondary to congenital, and
      acquired factors related to the gastrointestinal system. Herein, we report an
      extraordinary presentation of complete colonic obstruction due to extensive
      urinary retention in a 3-year-old boy. The possible underlying mechanism was
      detected as urinary infection in a child with horseshoe kidney. The treatment of
      the bladder symptoms and urinary infection relieved the obstruction of the colon.
      To our knowledge, especially in children, colonic obstruction due to urinary
      retention has not been reported in the literature. 

PMID- 24894929
TI  - Hypoplastic left heart syndrome in PAGOD syndrome.
AB  - Chromosomal abnormalities as well as non-cardiac anomalies have been identified
      as independent risk factors for surgical morbidity and mortality in Fontan
      palliation. The combination of malformations consisting of pulmonary hypoplasia,
      agonadism (sex reversal), omphalocele, and diaphragmatic defect is compatible
      with pulmonary artery and lung hypoplasia, agonadism, omphalocele, and
      diaphragmatic defect (PAGOD). Most cases have been associated with cardiac
      disease, particularly hypoplastic left heart syndrome (HLHS) that is potentially
      destined for Fontan palliation. Reported herein is the case of a Japanese female
      infant diagnosed with PAGOD syndrome along with HLHS (mitral atresia and aortic
      atresia), in whom intractable respiratory failure manifested as bilateral
      eventration of the diaphragm and presumed right lung hypoplasia. These
      characteristic pulmonary lesions associated with the syndrome precluded use of
      the Fontan pathway. 

PMID- 24894930
TI  - Bone marrow transplant for a girl with bone marrow failure and cerebral palsy.
AB  - Bone marrow transplantation (BMT) has been used with increasing frequency to
      treat congenital bone marrow failure syndrome (CBMFs) successfully. Decision to
      perform BMT, however, is difficult in the case of comorbidity because of regimen
      related toxicities. We describe here a child with CBMFs, severe cerebral palsy
      (CP) at Gross Motor Function Classification System level V and mental retardation
      (MR) who was transfusion dependent despite various medications. She underwent BMT
      from an HLA-1 locus-mismatched unrelated donor. Although engraftment was
      successful, no neurological improvement was seen 5 years after BMT. While CBMFs
      patients who have CP and MR could undergo transplantation safely, they may not
      benefit neurologically from BMT. 

PMID- 24894931
TI  - Hereditary spherocytosis diagnosed with the eosin-5'-maleimide binding test.
AB  - We describe three cases of hereditary spherocytosis (HS) diagnosed using the
      eosin-5'-maleimide (EMA) binding test and discuss the relevance of the EMA
      binding test. In Japan, this test is not widely used because the prevalence of HS
      is low. This test is a valuable screening test for the diagnosis of HS. 

PMID- 24894932
TI  - Successful treatment of fulminant Wilson's disease without liver transplantation.
AB  - Fulminant Wilson's disease (WD) is life-threatening. The revised WD prognostic
      index (RWPI) has been used to predict the severity of the disease, with a score
      >=11 indicating fatal outcome without liver transplantation (LTx). We here report
      the case of a 10-year-old female patient with fulminant WD (RWPI, 16) who
      recovered fully after plasma exchange and continuous hemodiafiltration, followed
      by treatment with copper chelate agents. To the best of our knowledge, there have
      been five fulminant WD patients with RWPI >= 11 including the present patient, in
      whom LTx was not done. Based on the therapeutic modalities in these five cases,
      non-surgical treatment (blood purification and copper chelate agents) may be able
      to avoid LTx in fulminant WD even with very high RWPI, although preparation for
      LTx is necessary. 

PMID- 24894933
TI  - Glycemic control and motor development in a patient with intermediate DEND.
AB  - The most common cause of neonatal diabetes, KCNJ11 gene mutation, can manifest as
      a neurological disorder. The most severe form consists of a constellation of
      developmental delay, epilepsy, and neonatal diabetes (DEND). Intermediate DEND
      (iDEND) refers to a milder presentation without epilepsy. We present a child with
      iDEND, for whom insulin injections were replaced with glibenclamide therapy at 17
      months of age because of poor glycemic control and delayed motor development.
      Three months after initiation of glibenclamide, HbA1c decreased from 10.2% to
      5.6%. Continuous glucose monitoring indicated that blood glucose fluctuations
      were suppressed while on glibenclamide. Furthermore, after initiating
      glibenclamide therapy, the developmental quotient (DQ) for motor ability markedly
      improved from 60 to 91, whereas the DQ for language and adoptive ability remained
      as they had been before the sulfonylurea treatment. Sulfonylurea treatment
      improved glycemic control and motor development in the present patient.

PMID- 24894934
TI  - Late vitamin K deficiency bleeding in an infant born at a maternity hospital.

PMID- 24894935
TI  - Post-H1N1 vaccine acute disseminated encephalomyelitis.

PMID- 24894936
TI  - Screening for anemia: is this ready for prime time?

PMID- 24894937
TI  - Challenging diagnosis between intussusception and necrotizing enterocolitis in
      premature infants.
AB  - Although necrotizing enterocolitis (NEC) is a frequently encountered entity in
      premature infants in the neonatal intensive care unit, intussusception is
      extremely rare. Abdominal distension, bilious/non-bilious gastric residuals and
      bloody stool are the common clinical findings of both entities. Here we present
      three cases of intussusception misdiagnosed as NEC, two of which were complicated
      with intestinal perforation. Similar clinical findings of NEC and intussusception
      leads to misdiagnosis and delay in treatment, particularly in premature infants
      with intussusception. 

PMID- 24894938
TI  - Bacterial meningitis after radiofrequency diathermy for adenoid hypertrophy.
AB  - A 6-year-old otherwise healthy girl who underwent radiofrequency diathermy for
      adenoid hypertrophy presented with fever on the same day and was diagnosed as
      having bacterial meningitis 2 days later. Culture of cerebrospinal fluid
      indicated that the pathogens were penicillin-sensitive Streptococcus pneumoniae
      and methicillin-sensitive Staphylococcus aureus. The serotype of the causative
      pneumococcus, 11A, was not covered by the 7-valent pneumococcal conjugate vaccine
      the patient had been inoculated with. Although not previously reported,
      radiofrequency diathermy for adenoid hypertrophy can be considered a risk factor
      for bacteremia and meningitis. 

PMID- 24894939
TI  - Datura stramonium intoxication in two children.
AB  - Datura stramonium is a toxic plant member of the Solanaceae family. Its
      consumption may result in severe anticholinergic toxicity. We report the
      intoxication of 5- and 4-year-old brothers with Datura stramonium, which
      presented in two different manners. The first child presented agitation,
      hallucination and mydriasis that improved rapidly with benzodiazepine medication.
      The second presented comatose, mydriasis and Babinski signs. Gastric lavage and
      activated charcoal administration were performed. The child was intubated and
      mechanically ventilated until consciousness improvement. Datura stramonium
      poisoning may be considered by physicians in case of acute onset of decreased
      consciousness or behaviour trouble associated with anticholinergic signs and
      symptoms. 

PMID- 24894940
TI  - Synovial sarcoma in a premature newborn.
AB  - Synovial sarcoma is rarely detected in infants, with an annual incidence of 0.5
      per million. Synovial sarcoma occurs more frequently in adolescents and young
      adults, with the majority of patients presenting between 15 and 40 years of age.
      It is extremely rare, however, in pediatric patients under 2 years of age. In the
      present study we examined a 3-day-old male infant born at 32 weeks who had a mass
      on his left arm. Synovial sarcoma was identified on histopathological and
      immunohistochemical analysis of biopsy material acquired from the mass. On whole
      body magnetic resonance imaging, diffuse metastases were detected in the
      bilateral lungs in the retroperitoneal zone, in bilateral suprarenal glands, the
      right liver lobe, the right kidney, and the brain. To our knowledge this is the
      youngest patient to be diagnosed with synovial sarcoma in the literature. 

PMID- 24894941
TI  - Utility of non-enhanced magnetic resonance imaging to detect acute
      pyelonephritis.
AB  - It has been established that enhanced computed tomography (CT) and (99m) Tc
      dimercaptosuccinic acid renal scintigraphy ((99m) Tc-DMSA scintigraphy) used in
      conjunction with single-photon emission CT is a useful tool for the diagnosis of
      acute pyelonephritis (APN). The utility of non-enhanced magnetic resonance
      imaging (MRI), however, has not been investigated extensively for the diagnosis
      of APN or renal abscess in children. We describe the case of a 23-month-old boy
      with suspected APN who received non-enhanced MRI. Whole body diffusion-weighted
      imaging (DWI) was used, and a background body-signal suppression sequence was
      applied. High-intensity focal lesions were identified on DWI and low-intensity
      lesions on the apparent diffusion coefficient map in the acute phase. This case
      suggested that non-enhanced MRI could be a useful tool for the diagnosis of APN
      in children, because it can avoid the risks of not only radiation exposure but
      also nephrogenic systemic fibrosis associated with gadolinium-based contrast
      agents, especially in infants. 

PMID- 24894942
TI  - Thyroglossal duct cyst accompanied by laryngomalacia and pulmonary sequestration.
AB  - A 2-month-old full-term female infant developed nasal stridor, which progressed
      to respiratory distress and poor sucking ability. Direct pharyngoscopy showed
      laryngomalacia and a midline cystic mass in the lingual region. The mass pressed
      on the epiglottis, causing dyspnea. Computed tomography incidentally revealed
      extralobar pulmonary sequestration. Direct deroofing of the lingual cyst and
      plication of the epiglottis were performed at 3 months of age, and the patient
      recovered from the respiratory distress. Histopathology of the cystic mass showed
      a thyroglossal duct cyst. Thoracoscopic resection of the pulmonary sequestration
      was then done at 17 months of age. Thyroglossal duct cysts in the lingual region
      may cause destabilization of the epiglottis and laryngomalacia, resulting in
      acquired respiratory obstruction. The combination of thyroglossal duct cyst,
      laryngomalacia, and pulmonary sequestration is rare; therefore, reports must be
      accumulated in order to explore the embryological origins of such cases. 

PMID- 24894943
TI  - An individual patient data metaanalysis of outcomes and prognostic factors after
      treatment of oligometastatic non-small-cell lung cancer.
AB  - INTRODUCTION/BACKGROUND: An individual patient data metaanalysis was performed to
      determine clinical outcomes, and to propose a risk stratification system, related
      to the comprehensive treatment of patients with oligometastatic NSCLC. MATERIALS
      AND METHODS: After a systematic review of the literature, data were obtained on
      757 NSCLC patients with 1 to 5 synchronous or metachronous metastases treated
      with surgical metastectomy, stereotactic radiotherapy/radiosurgery, or radical
      external-beam radiotherapy, and curative treatment of the primary lung cancer,
      from hospitals worldwide. Factors predictive of overall survival (OS) and
      progression-free survival were evaluated using Cox regression. Risk groups were
      defined using recursive partitioning analysis (RPA). Analyses were conducted on
      training and validating sets (two-thirds and one-third of patients,
      respectively). RESULTS: Median OS was 26 months, 1-year OS 70.2%, and 5-year OS
      29.4%. Surgery was the most commonly used treatment for the primary tumor (635
      patients [83.9%]) and metastases (339 patients [62.3%]). Factors predictive of OS
      were: synchronous versus metachronous metastases (P < .001), N-stage (P = .002),
      and adenocarcinoma histology (P = .036); the model remained predictive in the
      validation set (c-statistic = 0.682). In RPA, 3 risk groups were identified: low
      risk, metachronous metastases (5-year OS, 47.8%); intermediate risk, synchronous
      metastases and N0 disease (5-year OS, 36.2%); and high risk, synchronous
      metastases and N1/N2 disease (5-year OS, 13.8%). CONCLUSION: Significant OS
      differences were observed in oligometastatic patients stratified according to
      type of metastatic presentation, and N status. Long-term survival is common in
      selected patients with metachronous oligometastases. We propose this risk
      classification scheme be used in guiding selection of patients for clinical
      trials of ablative treatment.

PMID- 24894945
TI  - Response to Comments on "Anti-photoaging potential of botulinum toxin type A in
      UVB-induced premature senescence of human dermal fibroblasts in vitro through
      decreasing senescence-related proteins".

PMID- 24894944
TI  - EGFR exon 19 deletion mutations and systemic/central nervous system miliary
      metastasis: clinical correlations and response to therapy.

PMID- 24894946
TI  - Diagnostic value of magnetic resonance cholangiopancreatography for secondary
      common bile duct stones compared with laparoscopic trans-cystic common bile duct
      exploration.
AB  - BACKGROUND: The aim of this study was to evaluate the diagnostic potential of
      magnetic resonance cholangiopancreatography (MRCP) in preoperative patients with
      secondary common bile duct stones during the application of laparoscopic trans
      cystic common bile duct exploration (LTCBDE). MATERIAL AND METHODS: The clinical
      records of 255 patients were retrospectively analyzed. All patients included in
      the study were examined by MRCP 3 days prior to LTCBDE. RESULTS: Secondary bile
      duct stones were detected in 220 patients using LTCBDE. Of the patients diagnosed
      by MRCP, 141 were true-positive, 28 were true-negative, 7 were false-positive and
      79 were false-negative. The sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of MRCP for secondary common bile
      duct stones were 64.09%, 80.00%, 66.27%, 95.27%, and 26.17%, respectively. When
      the cases with muddy stones were excluded, the outcomes were 80.41%, 79.41%,
      69.23%, 94.44%, and 48.21%, respectively. When cases with stones <3 mm
      (inclusive) in diameter were excluded, the outcomes were 93.75%, 79.41%, 86.27%,
      93.75%, and 65.85%, respectively. When cases with stones <5 mm (inclusive) in
      diameter were excluded, the outcomes were 93.10%, 79.41%, 89.26%, 92.05%, and
      81.82%, respectively. CONCLUSIONS: The effectiveness of preoperative MRCP is
      overestimated for the diagnosis of secondary common bile duct stones,
      particularly for muddy and micro-stones.

PMID- 24894948
TI  - Preparation and investigation of high solid content PTX-loaded nanoparticles
      dispersion via nanoprecipitation method.
AB  - The improvement of the solid content of the hydrophobic drugs (such as paclitaxel
      (PTX), etc.) loaded nanoparticles (NPs) dispersion is important for enhancing
      drug-loaded efficiency and reducing the cost in production and application. A
      diblock copolymer methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone-co
      1,4,8-trioxa[4.6]spiro-9-undecanone) (mPECT) is synthesized via the ring-opening
      polymerization of epsilon-caprolactone and 1,4,8-trioxa[4.6]spiro-9-undecanone
      (TOSUO) with methoxy poly(ethyleneglycol) (mPEG) as the initiator. The chemical
      structures and thermal properties of mPECT are characterized by (1)HNMR, Fourier
      transform infrared (FT-IR), gel permeation chromatography, differential scanning
      calorimetry, etc. PEG45.45-b-P(C28.33-co-T5.38) (mPECT-2) is able to self
      assemble into stable NPs in water via nanoprecipitation method at a high solid
      content (<=25 wt%) and their freeze-dried powders can well re-disperse in water.
      The paclitaxel (PTX) is chosen as a hydrophobic drug model and successfully
      encapsulate into the mPECT-2 NPs via the same method at a high solid content. The
      encapsulation efficiency, cytotoxicity and in vitro release of PTX-loaded NPs are
      investigated. The results suggest that the behavior of the drug-loaded mPECT-2
      NPs prepared at a solid content of 25 wt% is similar to that of NPs prepared at a
      solid content of 1 wt%, which indicate that increasing solid content of polymer
      has no negative effect on the properties of NPs dispersion in application. In
      summary, the freeze-dried NPs prepared from the high solid content dispersion
      (<=25 wt%) has a good redispersibility and exhibits great potential in cost
      control of preparing NPs dispersion used as drug delivery system. 

PMID- 24894947
TI  - [Risk factor management of coronary heart disease : what is evidence-based?].
AB  - In patients with coronary heart disease the further course of the disease can be
      substantially influenced by means of a targeted treatment of risk factors. A
      reduction of hospital referrals, an improvement in quality of life and an
      extension in life expectation by secondary prophylactic measures have been well
      documented. In addition to an optimized medicinal therapy, an often drastic
      change in lifestyle with a focus on a consistent abstinence from nicotine, a
      healthy diet and regular physical exercise is necessary. Data from healthcare
      research show that these targets are only insufficiently achieved. The
      implementation of current guidelines should therefore be rigorously applied.
      There is a need for research particularly with respect to the prognostic
      significance of beta blocker therapy for patients with stable coronary heart
      disease and preserved left ventricular function, the prognostic significance of
      targeted weight loss for overweight or obese coronary heart disease patients, the
      effectiveness of psychosocial interventions in the various patient groups and
      their implementation into routine care. Research is also necessary with respect
      to optimization of structured rehabilitation programs and improvement in patient
      compliance. 

PMID- 24894949
TI  - A Snail1/Notch1 signalling axis controls embryonic vascular development.
AB  - Notch1-Delta-like 4 (Dll4) signalling controls vascular development by regulating
      endothelial cell (EC) targets that modulate vessel wall remodelling and arterial
      venous specification. The molecular effectors that modulate Notch signalling
      during vascular development remain largely undefined. Here we demonstrate that
      the transcriptional repressor, Snail1, acts as a VEGF-induced regulator of Notch1
      signalling and Dll4 expression. EC-specific Snail1 loss-of-function conditional
      knockout mice die in utero with defects in vessel wall remodelling in association
      with losses in mural cell investment and disruptions in arterial-venous
      specification. Snail1 loss-of-function conditional knockout embryos further
      display upregulated Notch1 signalling and Dll4 expression that is partially
      reversed by inhibiting gamma-secretase activity in vivo with Dll4 identified as a
      direct target of Snail1-mediated transcriptional repression. These results
      document a Snail1-Dll4/Notch1 axis that controls embryonic vascular development. 

PMID- 24894950
TI  - Ras-GRF2 mediates long-term potentiation, survival, and response to an enriched
      environment of newborn neurons in the hippocampus.
AB  - Hippocampal adult neurogenesis contributes to key functions of the dentate gyrus
      (DG), including contextual discrimination. This is due, at least in part, to the
      unique form of plasticity that new neurons display at a specific stage of their
      development when compared with the surrounding principal neurons. In addition,
      the contribution that newborn neurons make to dentate function can be enhanced by
      an increase in their numbers induced by a stimulating environment. However,
      signaling mechanisms that regulate these properties of newborn neurons are poorly
      understood. Here, we show that Ras-GRF2 (GRF2), a calcium-regulated exchange
      factor that can activate Ras and Rac GTPases, contributes to both of these
      properties of newborn neurons. Using Ras-GRF2 knockout mice and wild-type mice
      stereotactically injected with retrovirus containing shRNA against the exchange
      factor, we demonstrate that GRF2 promotes the survival of newborn neurons of the
      DG at approximately 1-2 weeks after their birth. GRF2 also controls the distinct
      form of long-term potentiation that is characteristic of new neurons of the
      hippocampus through its effector Erk MAP kinase. Moreover, the enhancement of
      neuron survival that occurs after mice are exposed to an enriched environment
      also involves GRF2 function. Consistent with these observations, GRF2 knockout
      mice display defective contextual discrimination. Overall, these findings
      indicate that GRF2 regulates both the basal level and environmentally induced
      increase of newborn neuron survival, as well as in the induction of a distinct
      form of synaptic plasticity of newborn neurons that contributes to distinct
      features of hippocampus-derived learning and memory.

PMID- 24894951
TI  - Rate of steroid double-bond reduction catalysed by the human steroid 5beta
      reductase (AKR1D1) is sensitive to steroid structure: implications for steroid
      metabolism and bile acid synthesis.
AB  - Human AKR1D1 (steroid 5beta-reductase/aldo-keto reductase 1D1) catalyses the
      stereospecific reduction of double bonds in Delta4-3-oxosteroids, a unique
      reaction that introduces a 90 degrees  bend at the A/B ring fusion to yield 5beta
      dihydrosteroids. AKR1D1 is the only enzyme capable of steroid 5beta-reduction in
      humans and plays critical physiological roles. In steroid hormone metabolism,
      AKR1D1 serves mainly to inactivate the major classes of steroid hormones. AKR1D1
      also catalyses key steps of the biosynthetic pathway of bile acids, which
      regulate lipid emulsification and cholesterol homoeostasis. Interestingly, AKR1D1
      displayed a 20-fold variation in the kcat values, with steroid hormone substrates
      (e.g. aldosterone, testosterone and cortisone) having significantly higher kcat
      values than steroids with longer side chains (e.g. 7alpha-hydroxycholestenone, a
      bile acid precursor). Transient kinetic analysis revealed striking variations up
      to two orders of magnitude in the rate of the chemistry step (kchem), which
      resulted in different rate determining steps for the fast and slow substrates. By
      contrast, similar Kd values were observed for representative fast and slow
      substrates, suggesting similar rates of release for different steroid products.
      The release of NADP+ was shown to control the overall turnover for fast
      substrates, but not for slow substrates. Despite having high kchem values with
      steroid hormones, the kinetic control of AKR1D1 is consistent with the enzyme
      catalysing the slowest step in the catabolic sequence of steroid hormone
      transformation in the liver. The inherent slowness of the conversion of the bile
      acid precursor by AKR1D1 is also indicative of a regulatory role in bile acid
      synthesis. 

PMID- 24894953
TI  - Optical coherence tomography as a tool for characterization of complex biological
      surfaces.
AB  - The advent of scanning electron microscopy has facilitated our understanding of
      the biology in relation to surface microstructure of many invertebrates. In
      recent years, interest in biomimetics and bio-inspired materials has further
      propelled the search for novel microstructures from natural surfaces. As this
      search widens in diversity to nurture deeper understanding of form and function,
      the need often arises to examine rare specimens. Unfortunately, most methods for
      characterization of the microtopography of natural surfaces are sacrificial, and
      as such, place limiting constraints on research progress in situations where only
      a few rare specimens are known, such as the rich resources lodged in natural
      history museum collections. In this paper, we introduce the use of optical
      coherence tomography (OCT) as a noninvasive tool for bioimaging surface
      microtopography of crab shells. The technique enables the capture of
      microstructures down to micron level using low coherence near-infrared light
      source. OCT has allowed surface microtopography imaging on crab shells to be
      carried out rapidly and in a nondestructive manner, compared to the scanning
      electron microscope technique. The microtopography of four preserved crab
      specimens from Acanthodromia margarita, Ranina ranina, Conchoecetes intermedius
      and Dromia dormia imaged using OCT were similar to images obtained from scanning
      electron microscope, showing that OCT imaging retains the overall morphological
      form during the scanning process. By comparing the physical lengths of the spinal
      structures from images obtained from OCT and scanning electron microscope, the
      results showed that dimensional integrity of the images captured from OCT was
      also maintained. 

PMID- 24894952
TI  - Transcript and metabolite profiling for the evaluation of tobacco tree and poplar
      as feedstock for the bio-based industry.
AB  - The global demand for food, feed, energy and water poses extraordinary challenges
      for future generations. It is evident that robust platforms for the exploration
      of renewable resources are necessary to overcome these challenges. Within the
      multinational framework MultiBioPro we are developing biorefinery pipelines to
      maximize the use of plant biomass. More specifically, we use poplar and tobacco
      tree (Nicotiana glauca) as target crop species for improving saccharification,
      isoprenoid, long chain hydrocarbon contents, fiber quality, and suberin and
      lignin contents. The methods used to obtain these outputs include GC-MS, LC-MS
      and RNA sequencing platforms. The metabolite pipelines are well established tools
      to generate these types of data, but also have the limitations in that only well
      characterized metabolites can be used. The deep sequencing will allow us to
      include all transcripts present during the developmental stages of the tobacco
      tree leaf, but has to be mapped back to the sequence of Nicotiana tabacum. With
      these set-ups, we aim at a basic understanding for underlying processes and at
      establishing an industrial framework to exploit the outcomes. In a more long term
      perspective, we believe that data generated here will provide means for a
      sustainable biorefinery process using poplar and tobacco tree as raw material. To
      date the basal level of metabolites in the samples have been analyzed and the
      protocols utilized are provided in this article.

PMID- 24894954
TI  - Nutritional status and its health-related factors among older adults in rural and
      urban areas.
AB  - AIM: To compare health-related characteristics, nutrition-related factors and
      nutritional status of older adults living in rural and urban counties of Taiwan.
      BACKGROUND: The older adult population of Taiwan is increasing. Furthermore,
      older people living in rural areas have shorter life expectancy and more chronic
      diseases than their urban counterparts. However, little is known about the health
      related characteristics, nutrition-related factors and nutritional status of
      older adults living in rural and urban areas of Taiwan, limiting nurses' ability
      to identify and care for older adults at risk of poor nutritional health. DESIGN:
      Cross-sectional, comparative. METHODS: Older adults were randomly selected from
      names of residents of an adjacent rural and urban area of northern Taiwan and
      having completing the 2009 health evaluation. From March-July 2010, older adult
      participants (N = 366) provided data on demographic and health-related
      information, nutritional self-efficacy, health locus of control and nutritional
      status. Data were analysed by descriptive statistics and compared using chi
      square and t-test. RESULTS: Older rural participants had significantly lower
      educational level, less adequate income, higher medication use, lower scores on
      self-rated health status and researcher-rated health status and lower self-rated
      healthy eating status than their urban counterparts. Moreover, rural participants
      had significantly lower nutritional self-efficacy, higher chance health locus of
      control and poorer nutritional status than their urban counterparts. CONCLUSIONS:
      Our results suggest that nurses should assess older adults living in rural areas
      for nutritional health and nutrition knowledge. Based on this assessment, nurses
      should develop easy, practical and accessible nutritional programmes for this
      population.

PMID- 24894958
TI  - Molecular mechanism of a hotdog-fold acyl-CoA thioesterase.
AB  - Thioesterases are enzymes that hydrolyze thioester bonds between a carbonyl group
      and a sulfur atom. They catalyze key steps in fatty acid biosynthesis and
      metabolism, as well as polyketide biosynthesis. The reaction molecular mechanism
      of most hotdog-fold acyl-CoA thioesterases remains unknown, but several
      hypotheses have been put forward in structural and biochemical investigations.
      The reaction of a human thioesterase (hTHEM2), representing a thioesterase family
      with a hotdog fold where a coenzyme A moiety is cleaved, was simulated by quantum
      mechanics/molecular mechanics metadynamics techniques to elucidate atomic and
      electronic details of its mechanism, its transition-state conformation, and the
      free energy landscape of the process. A single-displacement acid-base-like
      mechanism, in which a nucleophilic water molecule is activated by an aspartate
      residue acting as a base, was found, confirming previous experimental proposals.
      The results provide unambiguous evidence of the formation of a tetrahedral-like
      transition state. They also explain the roles of other conserved active-site
      residues during the reaction, especially that of a nearby histidine/serine pair
      that protonates the thioester sulfur atom, the participation of which could not
      be elucidated from mutation analyses alone. 

PMID- 24894959
TI  - Victim Participation in Intimate Partner Violence Prosecution: Implications for
      Safety.
AB  - Are intimate partner violence (IPV) victims safer if they use the criminal
      justice system? Concerns about perpetrator retaliation, in the face of data that
      protection orders can reduce future harm, make it important to understand how
      victim utilization (calling 911, talking to the prosecutor, and proceeding with
      prosecution) affects subsequent safety. We hypothesized participation would
      improve victims' safety, measured by decreases in subsequent IPV-related 911
      calls and/or emergency department visits. Findings support contact with the
      prosecutor's office was associated with reduction in police-reported IPV,
      regardless of the victim's wish to proceed. Policy implications support pro
      prosecution strategies coupled with victim contact.

PMID- 24894955
TI  - Role of duodenal iron transporters and hepcidin in patients with alcoholic liver
      disease.
AB  - Patients with alcoholic liver disease (ALD) often display disturbed iron indices.
      Hepcidin, a key regulator of iron metabolism, has been shown to be down-regulated
      by alcohol in cell lines and animal models. This down-regulation led to increased
      duodenal iron transport and absorption in animals. In this study, we investigated
      gene expression of duodenal iron transport molecules and hepcidin in three groups
      of patients with ALD (with anaemia, with iron overload and without iron overload)
      and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in
      duodenal biopsies by using real-time PCR and Western blot. Serum hepcidin levels
      were measured by using ELISA. Serum hepcidin was decreased in patients with ALD.
      At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly
      increased in ALD. This pattern was even more pronounced in the subgroups of
      patients without iron overload and with anaemia. Protein expression of FPN1
      paralleled the increase at the mRNA level in the group of patients with ALD.
      Serum ferritin was negatively correlated with DMT1 mRNA. The down-regulation of
      hepcidin expression leading to up-regulation of iron transporters expression in
      the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol
      consumption very probably causes suppression of hepcidin expression in patients
      with ALD. 

PMID- 24894964
TI  - Liver resection for young patients with large hepatocellular carcinoma: a single
      center experience from China.
AB  - BACKGROUND: To investigate retrospectively the clinicopathological
      characteristics and outcomes of young patients with large hepatocellular
      carcinoma after hepatectomy. METHODS: From January 2003 to December 2012, a total
      of 153 patients with large hepatocellular carcinoma (HCC) who received liver
      resection were included in the study. The clinicopathological features were
      analyzed retrospectively. The perioperative data were compared between those aged
      <40 years (the young group) and those aged >40 years (the older group).
      Prognostic factors and long-term survival were evaluated. RESULTS: The young
      group had more hepatitis B virus-related HCC than the older group (87.2% vs
      66.3%, P = 0.031). In the young group, 15 patients (21.5%) were overweight (body
      mass index 25 to 29.9 kg/m2) or obese (body mass index >=30 kg/m2), and 38
      patients (45.8%) were overweight or obese in the older group (P = 0.032). Other
      clinicopathological characteristics were similar between the two groups. The
      perioperative data showed that the older group had more pulmonary infection after
      hepatectomy. Vascular invasion and high Edmondson-Steiner grade were the
      independent prognostic factors for long-term survival. There was no statistical
      difference between the young group and the older group in overall survival and
      disease-free survival (P = 0.109 and P = 0.087, respectively). CONCLUSIONS: Liver
      resection for young patients with large HCC was safe and efficacious and should
      be recommended.

PMID- 24894963
TI  - Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent
      participants with less than daily methamphetamine use.
AB  - AIMS: Two previous randomized trials found an effect for bupropion in reducing
      methamphetamine use in the subgroup with lower frequency of methamphetamine use
      at baseline. This study aimed to replicate these results by comparing bupropion
      versus placebo in methamphetamine-dependent participants with less than daily
      methamphetamine use at baseline. METHODS: Methamphetamine-dependent volunteers
      reporting methamphetamine use on <=29 of past 30 days were randomized to
      bupropion 150 mg twice daily (n = 41) or placebo (n = 43) and out-patient
      counseling for 12 weeks. The primary outcome was the proportion achieving end-of
      treatment (EOT) methamphetamine abstinence (weeks 11 and 12) for bupropion versus
      placebo. A post-hoc analysis compared EOT abstinence by medication adherence
      assessed via plasma bupropion/hydroxybupropion level. RESULTS: There was no
      significant difference in EOT abstinence between bupropion (29%, 12 of 41) and
      placebo (14%, six of 43; P = 0.087). Among participants receiving bupropion, EOT
      abstinence was significantly higher in participants assessed as medication
      adherent by plasma bupropion/hydroxybupropion levels (54%, seven of 13) compared
      to non-adherent participants (18%, five of 28; P = 0.018). Medication adherence
      by plasma levels was low (32%). CONCLUSIONS: Bupropion may be efficacious for
      reducing methamphetamine in people with less than daily baseline methamphetamine
      use, but the evidence remains inconclusive.

PMID- 24894965
TI  - Patellar mobility can be reproducibly measured using ultrasound.
AB  - The present study was performed to examine the reliability of ultrasound in
      evaluating patellar mobility in the superior-inferior direction. Twelve healthy
      men volunteered for the study. Patellar mobility in the superior-inferior
      direction during isometric knee extension contraction with the knee immobilized
      in a semi-flexed knee brace was measured using ultrasound. Both intra-observer
      and inter-observer reliability were assessed by intra-class correlation
      coefficients (ICCs). Bland-Altman analysis was used for assessing agreement
      between measurements. ICC values were excellent for both intra-observer and inter
      observer reliability at 0.97 and 0.93, respectively. In 95 % of measurements, the
      same observer measured within -0.55 to 0.61 mm, while different observers
      measured within -0.82 to 0.85 mm. In conclusion, patellar mobility in the
      superior-inferior direction during an isometric knee extension exercise can be
      reproducibly measured using ultrasound. THE LEVEL OF EVIDENCE: VI (basic study of
      a novel evaluation method).

PMID- 24894966
TI  - [Obstructive sleep apnea syndrome in the elderly].
AB  - Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a common disease in the
      general population. However, original works on the SAHS in the elderly are few
      and their results are discordant. Studies show an increased prevalence of OSAHS
      with age, and despite this high prevalence, it remains under-diagnosed due to
      lack of knowledge of geriatric features of this disease and the frequency of
      comorbidities that may worsen as a result of nocturnal breathing problems but can
      also mask the symptoms necessary for positive diagnosis. The functional symptoms
      are dominated by neurological signs such as daytime hypersomnia and cognitive
      impairment often reported by those around the patient. The treatment is based
      mainly on continuous positive airway pressure which tolerance in elderly patients
      suffering from sleep apnea is similar to that of younger patients. Mandibular
      implants can be discussed depending on the severity of the condition. Surgical
      treatment is not indicated because of the increased frequency of complications. 

PMID- 24894967
TI  - [Surgery for thoracic tuberculosis].
AB  - Tuberculosis is mainly a medical disease. Surgery has been the unique therapeutic
      tool for a long time before the advent of specific antituberculous drugs, and the
      role of surgery was then confined to the treatment of the sequelae of
      tuberculosis and their complications. The resurgence of tuberculosis and the
      emergence of multidrug-resistant TB combined to immunosuppressed patients
      represent a new challenge for tuberculosis surgery. Surgery may be indicated for
      a diagnostic purpose in patients with pulmonary, pleural, mediastinal or thoracic
      wall involvement, or with a therapeutic purpose (drainage, resection, residual
      cavity obliteration). Modern imaging techniques and the advent of video-assisted
      thoracic surgery allowed a new approach of this pathology; the majority of
      diagnostic interventions and selected cases requiring lung resection can be
      performed through a mini-invasive approach. Patients proposed for aggressive
      surgery may be treated with the best results thanks to a good evaluation of the
      thoracic lesions, of the patients' nutritional, infectious and general status
      combined with a good coordination between the specialized medical team for an
      optimal preparation to surgery. 

PMID- 24894968
TI  - Social determinants of denture/bridge use: Japan gerontological evaluation study
      project cross-sectional study in older Japanese.
AB  - BACKGROUND: Studies suggest that using a denture/bridge may prevent disability in
      older people. However, not all older people with few remaining teeth use a
      denture/bridge. This cross-sectional study aimed to examine the social
      determinants which promote denture/bridge use among older Japanese. METHODS: A
      total of 54,388 (25,630 males and 28,758 females) community-dwelling individuals
      aged 65 or over, living independently, able to perform daily activities, and with
      19 or fewer teeth. The dependent variable was denture/bridge use. Socio
      demographics, number of teeth, present illness, social participation, social
      support, and social networks were used as individual-level independent variables.
      Data for social capital were aggregated and used as local district (n = 561 for
      males, n = 562 for females) -level independent variables. Number of dentists
      working in hospitals/clinics per population and population density were used as
      municipality (n = 28) -level independent variables. Three-level multilevel
      Poisson regression analysis was performed for each sex. RESULTS: High equivalent
      income, low number of teeth, present illness, and living in a municipality with
      high population density were significantly associated with denture/bridge use in
      both sexes in the fully adjusted models (p < 0.05). Denture/bridge use was
      significantly associated with high educational attainment in males and
      participating in social groups in females in the fully adjusted model (p < 0.05).
      No significant associations were observed between denture/bridge use and social
      capital. CONCLUSIONS: Denture/bridge use was significantly associated with high
      economic status and present illness in both sexes, high educational attainment in
      males, and participation in social groups in females among community-dwelling
      older Japanese after adjusting for possible confounders.

PMID- 24894969
TI  - Synthesis of triazolo-fused benzoxazepines and benzoxazepinones via Passerini
      reactions followed by 1,3-dipolar cycloadditions.
AB  - Azidobenzaldehydes can be used in Passerini three-component condensations to
      synthesize small collections of triazolo-fused heterocycles in an efficient and
      combinatorial fashion upon post-condensation azide-alkyne cycloadditions.
      Triazolo-fused benzoxazepinones were obtained in moderate to good overall yields
      with a concise two-step protocol. Triazolo-fused benzoxazepines were instead
      prepared by means of a longer, yet straightforward route comprising a Passerini
      reaction, hydrolysis of the ester moiety, O-alkylation with propargylic bromides,
      and 1,3-dipolar cycloaddition. 

PMID- 24894970
TI  - Acute Phase Response: Implication in ST-segment Elevation Myocardial Infarction.
AB  - We aimed to investigate the relation between serum inflammatory markers, 25OHvit
      D3 and oxidative stress markers, namely paraoxonase1-arylesterase (PON1-ARE),
      total antioxidant status (TAS) and total oxidant status (TOS) in 30 male patients
      with ST-elevation myocardial infarction(STEMI) . There was negative correlation
      between tumor necrosis factor alpha and ARE; positive correlations between serum
      amyloid A(SAA) and oxidative stress index, SAA and TOS, 25OHvit-D3 and ARE. There
      was no statistically significant correlation between inflammation makers,
      oxidative stress markers and Gensini score. The main finding of our study was the
      tendency of inflammation markers, and oxidative stress markers, to change in
      relatively clear opposite directions in STEMI. 

PMID- 24894971
TI  - CT-guided radiofrequency tumor ablation in children.
AB  - BACKGROUND: Image-guided radiofrequency ablation is a well-accepted technique of
      interventional oncology in adults. OBJECTIVE: To evaluate the efficacy and safety
      of CT-guided radiofrequency ablation as a minimally invasive treatment for
      metastatic neoplasms in children. MATERIALS AND METHODS: A total of 15
      radiofrequency ablation sessions were performed in 12 children and young adults
      (median age 9.5; range 5-18 years) with metastatic malignancies. Seven children
      and young adults had secondary hepatic lesions, three had pulmonary and two had
      bone lesions. Radiofrequency ablation was performed under conscious sedation.
      RESULTS: The median lesion size was 1.7 cm (range 1.3-2.8 cm). The median time
      for ablation was 8 min (range 7-10 min). Radiofrequency procedures were
      technically successful in all tumors. Postablation imaging immediately after, and
      1 month and 3 months after radiofrequency ablation showed total necrosis in all
      patients. At 6-month follow-up, three patients (all with lesion size >2 cm) had
      local recurrence and underwent a second radiofrequency ablation session. At 2
      year follow-up no patient had recurrence of the treated tumor. Post-ablation
      syndrome occurred in four children. No major complication occurred. CONCLUSION:
      CT-guided radiofrequency tumor ablation was safe and efficient for palliative
      treatment in our cohort of patients.

PMID- 24894972
TI  - What are the greatest challenges or barriers to applying post-mortem imaging in
      pediatric radiology?

PMID- 24894973
TI  - Surface-assisted large-scale ordering of DNA origami tiles.
AB  - The arrangement of DNA-based nanostructures into extended higher order assemblies
      is an important step towards their utilization as functional molecular materials.
      We herein demonstrate that by electrostatically controlling the adhesion and
      mobility of DNA origami structures on mica surfaces by the simple addition of
      monovalent cations, large ordered 2D arrays of origami tiles can be generated.
      The lattices can be formed either by close-packing of symmetric, non-interacting
      DNA origami structures, or by utilizing blunt-end stacking interactions between
      the origami units. The resulting crystalline lattices can be readily utilized as
      templates for the ordered arrangement of proteins. 

PMID- 24894975
TI  - Aortic coarctation repair in the adult.
AB  - Aortic coarctation can be repaired surgically or percutaneously. The decision
      should be made according to the anatomy and location of the coarctation, age of
      the patient, presence of other cardiac lesions, and other anatomic determinants
      (extensive collaterals or aortic calcification). This article reviews the
      different therapeutic options available, explaining the differences between
      children and adults, describing different approaches to the same disease,
      exemplified by three cases of nonclassic surgical approach and one percutaneous
      treatment.

PMID- 24894976
TI  - Copper-catalyzed synthesis of alpha-trifluoromethylthio-substituted ketones.
AB  - The CF3S-substituted moiety serves as an important structural element in many
      bioactive molecules. A versatile copper catalyst that allowed for
      trifluoromethylthiolation of primary and secondary alpha-bromoketones is
      described. The reaction with readily available elemental sulfur and CF3SiMe3
      afforded a broad scope and moderate to good yields of alpha-trifluoromethylthio
      substituted ketones. This procedure represents a very operationally simple yet
      powerful strategy for the synthesis of alpha-trifluoromethylthio-substituted
      ketones, a useful and versatile class of synthetic synthons. 

PMID- 24894974
TI  - Comparative immunophenotyping of equine multipotent mesenchymal stromal cells: an
      approach toward a standardized definition.
AB  - Horses are an approved large animal model for therapies of the musculoskeletal
      system. Especially for tendon disease where cell-based therapy is commonly used
      in equine patients, the translation of achieved results to human medicine would
      be a great accomplishment. Immunophenotyping of equine mesenchymal stromal cells
      (MSCs) remains the last obstacle to meet the criteria of the International
      Society for Cellular Therapy (ISCT) definition of human MSCs. Therefore, the
      surface antigen expression of CD 29, CD 44, CD 73, CD 90, CD 105, CD 14, CD 34,
      CD 45, CD 79alpha, and MHC II in equine MSCs from adipose tissue, bone marrow,
      umbilical cord blood, umbilical cord tissue, and tendon tissue was analyzed using
      flow cytometry. Isolated cells from the different sources and donors varied in
      their expression pattern of MSC-defining antigens. In particular, CD 90 and 105
      showed most heterogeneity. However, cells from all samples were robustly positive
      for CD 29 and CD 44, while being mostly negative for CD 73 and the exclusion
      markers CD 14, CD 34, CD 45, CD 79alpha and MHC II. Furthermore, it was evident
      that enzymes used for cell detachment after in vitro-culture affected the
      detection of antigen expression. These results emphasize the need of
      standardization of MSC isolation, culturing, and harvesting techniques. As the
      equine MSCs did not meet all criteria the ISCT defined for human MSCs, further
      investigations for a better characterization of the cell type should be
      conducted.

PMID- 24894977
TI  - CK2-dependent inhibitory phosphorylation is relieved by Ppt1 phosphatase for the
      ethanol stress-specific activation of Hsf1 in Saccharomyces cerevisiae.
AB  - Ethanol, the major fermentation product of Saccharomyces cerevisiae, has long
      been known as an inducer of heat shock response, but the underlying mechanisms by
      which ethanol activates heat shock transcription factor (HSF) are not well
      understood. We demonstrate that CK2-dependent phosphorylation on S608 is an
      ethanol stress-specific repression mechanism of Hsf1, which does not affect the
      basal or heat-induced activity of Hsf1. This repression is relieved by
      dephosphorylation by Ppt1 which directly interacts with Hsf1 via its
      tetratricopeptide repeat (TPR) domain. In response to ethanol stress, PPT1
      deletion and CK2 overexpression exert synergistic inhibitory effects on Hsf1
      activation, whereas Hsf1(S608A) mutant shows enhanced activation. Therefore,
      regulation of the Hsf1 S608 phosphorylation status by reciprocal actions of CK2
      and Ppt1 might play an important role to determine Hsf1 sensitivity towards
      ethanol stress.

PMID- 24894978
TI  - Evidence for solar cycles in a late Holocene speleothem record from Dongge Cave,
      China.
AB  - The association between solar activity and Asian monsoon (AM) remains unclear.
      Here we evaluate the possible connection between them based on a precisely-dated,
      high-resolution speleothem oxygen isotope record from Dongge Cave, southwest
      China during the past 4.2 thousand years (ka). Without being adjusted
      chronologically to the solar signal, our record shows a distinct peak-to-peak
      correlation with cosmogenic nuclide (14)C, total solar irradiance (TSI), and
      sunspot number (SN) at multi-decadal to centennial timescales. Further cross
      wavelet analyses between our calcite delta(18)O and atmospheric (14)C show
      statistically strong coherence at three typical periodicities of ~80, 200 and 340
      years, suggesting important roles of solar activities in modulating AM changes at
      those timescales. Our result has further indicated a better correlation between
      our calcite delta(18)O record and atmospheric (14)C than between our record and
      TSI. This better correlation may imply that the Sun-monsoon connection is
      dominated most likely by cosmic rays and oceanic circulation (both associated to
      atmospheric (14)C), instead of the direct solar heating (TSI). 

PMID- 24894979
TI  - Normal nasal airflow.

PMID- 24894981
TI  - Isolated frontal sinusitis treated using an anterior-to-ethmoidal bulla surgical
      approach.
AB  - Traditional frontal sinus surgery is associated with a significant trauma.
      Herein, we have discussed the feasibility, technique, and efficacy of a minimally
      invasive anterior-to-ethmoidal bulla surgical approach performed under nasal
      endoscopy to treat isolated frontal sinusitis. Fifteen patients with isolated
      frontal sinusitis underwent the anterior-to-ethmoidal bulla surgical procedure
      under general anesthesia. The opening of the frontal sinus was located by frontal
      mini-trephination in 1 patient. The effects of the operation were evaluated by
      regular postoperative follow-up. The average postoperative follow-up period was
      12.7 months (range 6-24 months). The postoperative symptom of headache was
      completely resolved in all 15 patients, and 12 patients had good opening of the
      frontal sinus and complete epithelization was observed by nasal endoscopy. The
      frontal sinus of 3 patients was not opened, but these patients did not show
      subjective symptoms. The anterior-to-ethmoidal bulla surgical approach is ideal
      for isolated frontal sinusitis.

PMID- 24894980
TI  - Profiles of thyrotropin, thyroid hormones, follicular cells and type I deiodinase
      gene expression during ontogenetic development of tilapia larvae and juveniles.
AB  - The aims of the present study are to determine whether triiodothyronine (T3)
      and/or thyroxine (T4) in tilapia larvae is gifted through the mother, and to
      investigate the change profiles of thyrotropin (TSH), thyroid follicular cells
      and type I deiodinase (D1) gene expression following larval development. T3 and
      T4 contents were measured using radioimmunoassay, thyrotropin was observed using
      immunocytochemistry, and the D1 gene was cloned and measured using real-time PCR.
      Results indicated that the beta-TSH-immunoreactive cells (thyrotropin ICC)
      signals were detected at 9 dph (i.e., 9 days of post-hatching). Thyroid
      follicular cells were observed first at 3 dph, while the T3 contents of the whole
      body gradually decreased before 11 dph. T4 contents were detected until 13 dph,
      with higher secretion during 19-21 dph. In addition, the T3 synthesis was not
      inhibited by thiourea (TU) before 13 dph, but the TU response in the larvae
      appeared after 13 dph. Type I deiodinase (D1: GenBank accession number KC591724)
      was found to contain 2444 bases and encoded 248 amino acids. The D1 mRNA
      expression began to increase at 13 dph, with a higher expression during 15-19
      dph. These results suggested that the T3 contents were maternally derived before
      13 dph. Both thyroid hormonal changes and some parameters related to thyroid
      hormone synthesis in ontogenetic tilapia are discussed.

PMID- 24894982
TI  - Potential of mesenchymal stem cells by adenovirus-mediated erythropoietin gene
      therapy approaches for bone defect.
AB  - Regeneration of large bone defects is a common clinical problem. Recent studies
      have shown that mesenchymal stem cells (MSCs) have emerged as a promising
      alternative to traditional surgical techniques. However, it is still a key
      question how to enhance the osteogenic potential of MSCs for possible clinical
      trials. The aim of the present study was to investigate the effect of adenovirus
      mediated erythropoietin (Ad-EPO) transfer on BMSCs, we performed extensive in
      vitro/in vivo assays in this study. Flow cytometry analysis and the result of MTT
      showed that EPO could promote BMSCs proliferation. QPCR data demonstrated that
      EPO increased expressions of Runx2, Sp7, and Col1 in osteoblast at various time
      points and also increased alkaline phosphatase activity and the calcium
      deposition. These results indicate that EPO can increase the differentiation of
      osteoblast. Importantly, in vivo assays clearly demonstrate that EPO can
      efficiently induce new bone formation in the bone defect model. Our results
      strongly suggest that EPO can affect osteoblast differentiation and play
      important roles in bone regeneration leading to an increase in bone formation. 

PMID- 24894983
TI  - Special focus: Archaea.

PMID- 24894986
TI  - The modulation of semantic transparency on the recognition memory for two
      character Chinese words.
AB  - This study demonstrated that semantic transparency as a linguistic property
      modulates the recognition memory for two-character Chinese words, with opaque
      words (i.e., words whose meanings cannot be derived from constituent characters
      e.g., "[/guang/, light][/gun/, stick]", bachelor) remembered better than
      transparent words (i.e., words whose meanings can be derived from constituent
      characters-e.g., "[/cha/, tea][/bei/, cup]", teacup). In Experiment 1, the
      participants made lexical decisions on transparent words, opaque words, and
      nonwords in the study and then engaged in an old/new recognition test. Experiment
      2 employed a concreteness judgment as the encoding task to ensure equivalent
      semantic processing for opaque and transparent words. In Experiment 3, the
      neighborhood size of the two-character words was manipulated together with their
      semantic transparency. In all three experiments, opaque words were found to be
      better remembered than transparent words. We concluded that the conceptual
      incongruence between the meanings of a whole word and its constituent characters
      made opaque words more distinctive and, hence, better remembered than transparent
      words.

PMID- 24894987
TI  - Regulation of serine protease inhibitor Kazal type-5 (SPINK5) gene expression in
      the keratinocytes.
AB  - OBJECTIVES: Serine protease inhibitor Kazal type-5 (SPINK5) plays a crucial role
      in deciding the timing of desquamation of the skin. Its gene expression is
      limited at the very surface of the stratum granulosum (SG), whereas expression of
      kallikreins (KLKs) encoding proteases is usually found throughout the stratum
      spinosum and SG. METHODS: To explore the difference in expression regulation of
      these proteases/inhibitors, the function of SPINK5 promoter was examined using
      luciferase assay. RESULTS: Luciferase assay targeting the SPINK5 promoters
      (nucleotide -676/-532 and -318/-146 from the major transcription start site)
      showed high intensity in NHEK human keratinocyte. These two sites had neither
      common cis-elements nor GATA3 element but electrophoretic mobility shift assay
      showed similar retardation bands. Moreover, DNA footprinting did not display
      specific protected bands. Thus, we could not identify cis-element(s) that
      controlled these elements. Differentiation induced by high Ca(2+) medium failed
      to alter their luciferase activities. Transfection of GATA3 expressing vector
      significantly but slightly increased them and that of vector expressing its
      dominant negative form decreased. CONCLUSIONS: Although GATA3 is reportedly
      important for inhibition of proliferation and induction of differentiation of
      keratinocytes, its effect on SPINK5 expression was indirect and GATA3 alone was
      insufficient for final differentiation of keratinocytes where full SPINK5
      expression was observed.

PMID- 24894990
TI  - The significant change and reform in PRChina.

PMID- 24894989
TI  - Light-responsive control of bacterial gene expression: precise triggering of the
      lac promoter activity using photocaged IPTG.
AB  - Light can be used to control numerous cellular processes including protein
      function and interaction as well as gene expression in a non-invasive fashion and
      with unprecedented spatiotemporal resolution. However, for chemical phototriggers
      tight, gradual, and homogeneous light response has never been attained in living
      cells. Here, we report on a light-responsive bacterial T7 RNA polymerase
      expression system based on a photocaged derivative of the inducer molecule
      isopropyl-beta-d-thiogalactopyranoside (IPTG). We have comparatively analyzed
      different Escherichia coli lac promoter-regulated expression systems in batch and
      microfluidic single-cell cultivation. The lacY-deficient E. coli strain
      Tuner(DE3) harboring additional plasmid-born copies of the lacI gene exhibited a
      sensitive and defined response to increasing IPTG concentrations. Photocaged IPTG
      served as a synthetic photo-switch to convert the E. coli system into an
      optogenetic expression module allowing for precise and gradual light-triggering
      of gene expression as demonstrated at the single cell level. 

PMID- 24894988
TI  - Granulocytic myeloid derived suppressor cells expand in human pregnancy and
      modulate T-cell responses.
AB  - Immune tolerance toward the semiallogeneic fetus plays a crucial role in the
      maintenance of pregnancy. Myeloid-derived suppressor cells (MDSCs) are innate
      immune cells characterized by their ability to modulate T-cell responses.
      Recently, we showed that MDSCs accumulate in cord blood of healthy newborns, yet
      their role in materno-fetal tolerance remained elusive. In the present study, we
      demonstrate that MDSCs with a granulocytic phenotype (GR-MDSCs) are highly
      increased in the peripheral blood of healthy pregnant women during all stages of
      pregnancy compared with nonpregnant controls, whereas numbers of monocytic MDSCs
      were unchanged. GR-MDSCs expressed the effector enzymes arginase-I and iNOS,
      produced high amounts of ROS and efficiently suppressed T-cell proliferation.
      After parturition, GR-MDSCs decreased within a few days. In combination, our
      results show that GR-MDSCs expand in normal human pregnancy and may indicate a
      role for MDSCs in materno-fetal tolerance. 

PMID- 24894992
TI  - Fluoroscopy-based laser guidance system for linear surgical tool insertion depth
      control.
AB  - PURPOSE: In most orthopedic surgeries, knowing how far to insert surgical tools
      is crucial. The objective of this study was to provide guidance information on
      depth without tracking surgical tools. A previously developed laser guidance
      system for linear surgical tool insertion uses two laser beams that display the
      insertion point and orientation on the skin surface. However, the system only
      provides 4 degrees of freedom guidance (an entry point on the planned pathway
      line and the orientation) but do not inform surgeons on the ideal insertion
      depth. METHOD: A 5-DOF guidance method was developed to provide guidance
      information by direct projection onto the surgical area using laser beams without
      tracking markers. A position and orientation guidance performed by two laser
      beams and depth guidance performed by a single laser beam are appeared on the
      surgical area in turn. However, depth point appears on the surgical tool side
      face with some error because of tool radius. Using the actual depth position,
      insertion path vector and location of the laser sources, the correct depth point
      on the tool's surface is calculated by the proposed method. So, this system can
      indicate and navigate the 5-DOF which is planning path and the correct depth
      point. RESULTS: An evaluation of the accuracy of depth guidance revealed a depth
      guidance error of 0.55+/-0.29 mm and results from phantom target insertions
      revealed overall system accuracies of 1.44 +/- 1.09 mm, 0.91 degrees  +/- 0.82
      degrees . In addition, overall system accuracies of application feasibility
      experiment under the X-ray condition were 1.94 +/- 0.98mm, 1.39 degrees  +/- 1.30
      degrees . CONCLUSION: A new surgical tool depth insertion method was developed
      using a fluorolaser guidance system. This tool informs surgeons of the surgical
      tool tip depth assuming that the insertion point and orientation are correct. The
      new method was tested successfully in vitro.

PMID- 24894995
TI  - MLK3 is part of a feedback mechanism that regulates different cellular responses
      to reactive oxygen species.
AB  - Reactive oxygen species (ROS) influence diverse cellular processes, including
      proliferation and apoptosis. Both endogenous and exogenous ROS activate signaling
      through mitogen-activated proteins kinase (MAPK) pathways, including those
      involving extracellular signal-regulated kinases (ERKs) or c-Jun N-terminal
      kinases (JNKs). Whereas low concentrations of ROS generally stimulate
      proliferation, high concentrations result in cell death. We found that low
      concentrations of ROS induced activating phosphorylation of ERKs, whereas high
      concentrations of ROS induced activating phosphorylation of JNKs. Mixed lineage
      kinase 3 (MLK3, also known as MAP3K11) directly phosphorylates JNKs and may
      control activation of ERKs. Mathematical modeling of MAPK networks revealed a
      positive feedback loop involving MLK3 that determined the relative
      phosphorylation of ERKs and JNKs by ROS. Cells exposed to an MLK3 inhibitor or
      cells in which MLK3 was knocked down showed increased activation of ERKs and
      decreased activation of JNKs and were resistant to cell death when exposed to
      high concentrations of ROS. Thus, the data indicated that MLK3 is a critical
      factor controlling the activity of kinase networks that control the cellular
      responses to different concentrations of ROS. 

PMID- 24894994
TI  - Store-operated calcium entry promotes the degradation of the transcription factor
      Sp4 in resting neurons.
AB  - Calcium (Ca(2+)) signaling activated in response to membrane depolarization
      regulates neuronal maturation, connectivity, and plasticity. Store-operated
      Ca(2+) entry (SOCE) occurs in response to depletion of Ca(2+) from endoplasmic
      reticulum (ER), mediates refilling of this Ca(2+) store, and supports Ca(2+)
      signaling in nonexcitable cells. We report that maximal activation of SOCE
      occurred in cerebellar granule neurons cultured under resting conditions and that
      this Ca(2+) influx promoted the degradation of transcription factor Sp4, a
      regulator of neuronal morphogenesis and function. Lowering the concentration of
      extracellular potassium, a condition that reduces neuronal excitability,
      stimulated depletion of intracellular Ca(2+) stores, resulted in the
      relocalization of the ER Ca(2+) sensor STIM1 into punctate clusters consistent
      with multimerization and accumulation at junctions between the ER and plasma
      membrane, and induced a Ca(2+) influx with characteristics of SOCE. Compounds
      that block SOCE prevented the ubiquitylation and degradation of Sp4 in neurons
      exposed to a low concentration of extracellular potassium. Knockdown of STIM1
      blocked degradation of Sp4, whereas expression of constitutively active STIM1
      decreased Sp4 abundance under depolarizing conditions. Our findings indicated
      that, in neurons, SOCE is induced by hyperpolarization, and suggested that this
      Ca(2+) influx pathway is a distinct mechanism for regulating neuronal gene
      expression. 

PMID- 24894997
TI  - Expression and cellular localization of the classical progesterone receptor in
      healthy and amyotrophic lateral sclerosis affected spinal cord.
AB  - BACKGROUND AND PURPOSE: Previous studies have suggested that elevated
      progesterone levels are associated with a slower disease course in amyotrophic
      lateral sclerosis (ALS). Given that the effects of progesterone are mediated in
      part by the classical progesterone receptor (PR), the expression and cellular
      localization of the A and B isoforms (PR-A and PR-B, respectively) of the PR in
      control (neuropathologically normal) and ALS-affected spinal cord (SC) were
      examined. METHODS: Semi-quantitative RT-PCR, immunohistochemistry and
      immunofluorescence analyses of the cervical and lumbar SC of post-mortem ALS
      patients (n = 19) and control subjects (n = 10) were performed. Primers and
      antibodies used allowed the detection of both PR-A and PR-B isoforms together (PR
      A+B) or PR-B isoform alone. RESULTS: Lumbar PR-A+B and cervical PR-B mRNA
      expression were significantly higher in ALS than controls. In both ALS and
      controls, PR-A+B immunoreactivity (IR) was occasionally detected in motor
      neurons. In contrast, PR-A+B IR was prominent in axonal processes and vessels.
      This was more evident in nerve roots and large arteries in ALS compared with
      controls. Colocalization of PR-A+B with markers of neurons, axonal processes and
      vascular endothelium was also observed. CONCLUSIONS: Evidence that both PR-A and
      PR-B isoforms are expressed in the human SC is provided, with some regional
      variation in isoform expression between ALS and controls. The IR was more
      prominent in nerve roots and large arteries in ALS, suggesting a potential role
      in the degenerative process.

PMID- 24894996
TI  - The ABA receptor PYL8 promotes lateral root growth by enhancing MYB77-dependent
      transcription of auxin-responsive genes.
AB  - The phytohormone abscisic acid (ABA) regulates plant growth, development, and
      abiotic stress responses. ABA signaling is mediated by a group of receptors known
      as the PYR1/PYL/RCAR family, which includes the pyrabactin resistance 1-like
      protein PYL8. Under stress conditions, ABA signaling activates SnRK2 protein
      kinases to inhibit lateral root growth after emergence from the primary root.
      However, even in the case of persistent stress, lateral root growth eventually
      recovers from inhibition. We showed that PYL8 is required for the recovery of
      lateral root growth, following inhibition by ABA. PYL8 directly interacted with
      the transcription factors MYB77, MYB44, and MYB73. The interaction of PYL8 and
      MYB77 increased the binding of MYB77 to its target MBSI motif in the promoters of
      multiple auxin-responsive genes. Compared to wild-type seedlings, the lateral
      root growth of pyl8 mutant seedlings and myb77 mutant seedlings was more
      sensitive to inhibition by ABA. The recovery of lateral root growth was delayed
      in pyl8 mutant seedlings in the presence of ABA, and the defect was rescued by
      exposing pyl8 mutant seedlings to the auxin IAA (3-indoleacetic acid). Thus, PYL8
      promotes lateral root growth independently of the core ABA-SnRK2 signaling
      pathway by enhancing the activities of MYB77 and its paralogs, MYB44 and MYB73,
      to augment auxin signaling. 

PMID- 24894998
TI  - Anti-JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS)
      trial.
AB  - BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) is
      caused by reactivation of JC virus (JCV) infection due to combined host and viral
      factors. Anti-JCV antibodies provide a means to assess JCV exposure and stratify
      PML risk. The reported seroprevalence of anti-JCV antibodies varies from 39% to
      91% depending on assay methodology and population studied. A two-step anti-JCV
      antibody assay (STRATIFY JCVTM; Focus Diagnostics, Cypress, CA, USA) detected
      anti-JCV antibodies in approximately 55% of multiple sclerosis (MS) patients.
      This study describes the prevalence of anti-JCV antibodies in a large,
      multinational MS population. METHODS: This cross-sectional epidemiology study was
      designed to enroll a minimum of 2000 patients with an MS diagnosis of any type,
      irrespective of treatment, from Europe, Canada and Australia. Anti-JCV antibody
      prevalence was determined by STRATIFY JCV; the effects of demographic and disease
      characteristics were evaluated. RESULTS: A total of 7724 patients from 10
      countries participated in the study. Overall anti-JCV antibody prevalence was
      57.1% (95% confidence interval 56.0%-58.2%). Seroprevalence was significantly
      associated with increasing age, gender and country of current residence (P <
      0.0001). No significant differences in anti-JCV antibody prevalence were
      associated with MS disease characteristics, including duration and type of MS and
      number and duration of MS therapies. CONCLUSIONS: Overall seroprevalence of anti
      JCV antibodies in MS patients from Europe, Canada and Australia was consistent
      with previous studies using the STRATIFY JCV assay. Anti-JCV prevalence differed
      significantly by age, gender and country, but no geographical pattern was
      evident. Disease and treatment type were not associated with differences in anti
      JCV antibody status.

PMID- 24894999
TI  - Clinical characteristics and prognostic significance of chronic obstructive
      pulmonary disease in patients with atrial fibrillation: results from a
      multicenter atrial fibrillation registry study.
AB  - OBJECTIVES: Atrial fibrillation (AF) and chronic obstructive pulmonary disease
      (COPD) are 2 common morbidities and often coexist. Studies have shown that COPD
      is a risk factor for cardiovascular disease, but the characteristics in patients
      with COPD and AF, as well as the impact of COPD on the outcomes of AF were
      lacking. The aim of present study was to analyze the clinical characteristics and
      to evaluate the association of COPD with 1-year outcomes in patients with AF.
      DESIGN: Longitudinal observational study. PARTICIPANTS: A total of 1975
      consecutive patients with AF were registered. Patients were divided into COPD
      group and non-COPD group according to whether AF coexisted with COPD.
      MEASUREMENTS: Outcome measures included all-cause mortality, stroke, and major
      adverse events (MAE) during 1-year follow-up. RESULTS: A group of 227 (11.5%)
      patients had concomitant COPD. Compared with non-COPD patients, patients with
      COPD were older and tended to have other coexisting cardiovascular morbidities,
      and had a significantly higher percentage of smoking history. Anticoagulation
      with warfarin was adopted by only a few patients both with and without COPD.
      During 1-year follow-up, the all-cause mortality and major adverse event rate in
      the COPD group were significantly higher than that of non-COPD group (26.9% vs
      12.3%, P < .001 and 25.6% vs 19.1%, P = .027, respectively), whereas the
      incidence of stroke in the 2 groups was comparable (7.9% vs 7.4%, P = .788).
      Moreover, the cause-specific mortality between the 2 groups was comparable. After
      multivariate adjustments, COPD was still an independent risk factor for both 1
      year all-cause mortality [hazard rate (HR) = 1.491, 95% confidence interval (CI)
      1.110-2.002, P = .008] and cardiovascular mortality (HR = 1.595, 95% CI 1.071
      2.376, P = .022), but not a risk factor for stroke (HR = 0.879, 95% CI 0.527
      1.464, P = .620). CONCLUSIONS: Anticoagulation treatment is inadequate in
      patients with AF and COPD. The presence of COPD in patients with AF is an
      independent risk factor for 1-year all-cause mortality and cardiovascular
      mortality but not a risk factor for stroke.

PMID- 24895000
TI  - Rare case of catastrophic diffuse hemorrhage complicating sepsis and meningitis
      due to Pasteurella stomatis in an elderly woman mimicking hemorrhagic septicemia.

PMID- 24895001
TI  - An educational intervention on drug use in nursing homes improves health outcomes
      resource utilization and reduces inappropriate drug prescription.
AB  - OBJECTIVE: Inappropriate drug prescription is a common problem in people living
      in nursing homes and is linked to adverse health outcomes. This study assessed
      the effect of an educational intervention directed to nursing home physicians in
      reducing inappropriate prescription and improving health outcomes and resource
      utilization. DESIGN: Prospective, randomized, multicenter study. SETTING: A
      private organization of nursing homes in Spain. PARTICIPANTS: Sixty nursing home
      physicians caring for approximately 3900 nursing home residents in 37 centers
      were randomized to receive an educational intervention (30) or as a control group
      (30). INTERVENTION: 10 hours educational program, followed by on demand support
      by phone. OUTCOME MEASUREMENTS: Outcomes were assessed in 1018 randomly selected
      nursing home residents. Appropriateness of drug use [measured by the Screening
      Tool of Older Persons Prescriptions (STOPP) and Screening Tool to Alert Doctors
      to Right Treatment (START) criteria], incidence of selected geriatric syndromes
      (falls, delirium) and health resource utilization (visits to physicians and
      nursing homes, visits to the emergency room, days of hospitalization) were
      recorded for 3 months before the intervention started and 3 months after the
      intervention finished. RESULTS: O total of 716 residents finished the study (344
      cared for by the intervention group physicians, 372 cared for by control
      physicians). Mean age was 84.4 +/- 12.7 years; 73% were women. The mean number of
      inappropriate drugs (STOPP criteria) was higher at the end of the study in the
      control than in the intervention group (1.29 +/- 1.56 vs 0.81 +/- 1.13), as was
      the number of residents on 6 or more drugs (76.5% vs.67.0%), using antipsychotics
      (9.1% vs 3.2%) or duplicate medications (32.5% vs 9.2%). The number of fallers
      increased in the control group (from 19.3% to 28%) and did not significantly
      change in the intervention group (from 25.3% to 23.9%); the number of residents
      with delirium increased in the control group (from 3.8% to 9.1%) and decreased in
      the intervention group (from 6.1% to 3.2%). The number of visits to a physician
      did not change in the control group (-0.22, P = .3) but were significantly
      reduced in the intervention group (-0.76, P = .01), the same happened with the
      number of visits to a nurse (-0.38, P = .4 in controls, -1.43 in the intervention
      group, P < .001). Visits to the emergency room and days in hospital significantly
      increased in the control group (+0.12 and +0.38) but were unchanged in the
      intervention group (+0.03 and +0.01). CONCLUSIONS: An educational intervention on
      drug use is feasible in nursing home physicians and improves the use of
      inappropriate drugs, use of antipsychotics, and drug duplications in their
      residents. It may also improve the risk of delirium and falls, and reduce the use
      of health care resources.

PMID- 24895002
TI  - Advance care planning: just do it!

PMID- 24895003
TI  - Lipid metabolites as metabolic messengers in inter-organ communication.
AB  - Metabolic homeostasis is achieved through coordinated regulation across several
      tissues. Studies using mouse genetic models have shown that perturbation of
      specific pathways of lipid metabolism in metabolically active tissues impacts
      systemic metabolic homeostasis. The use of metabolomic technologies combined with
      genetic models has helped to identify several potential lipid mediators that
      serve as metabolic messengers to communicate energy status and modulate substrate
      utilization among tissues. When provided exogenously, these lipid metabolites
      exhibit biological effects on glucose and lipid metabolism, indicating a
      therapeutic potential for treating metabolic diseases. In this review we
      summarize recent advances in inter-organ communication through novel mechanisms,
      with a focus on lipid mediators synthesized de novo or derived from dietary
      sources, and discuss challenges and future directions. 

PMID- 24895004
TI  - The FlyBar: administering alcohol to flies.
AB  - Fruit flies (Drosophila melanogaster) are an established model for both alcohol
      research and circadian biology. Recently, we showed that the circadian clock
      modulates alcohol sensitivity, but not the formation of tolerance. Here, we
      describe our protocol in detail. Alcohol is administered to the flies using the
      FlyBar. In this setup, saturated alcohol vapor is mixed with humidified air in
      set proportions, and administered to the flies in four tubes simultaneously.
      Flies are reared under standardized conditions in order to minimize variation
      between the replicates. Three-day old flies of different genotypes or treatments
      are used for the experiments, preferably by matching flies of two different time
      points (e.g., CT 5 and CT 17) making direct comparisons possible. During the
      experiment, flies are exposed for 1 hr to the pre-determined percentage of
      alcohol vapor and the number of flies that exhibit the Loss of Righting reflex
      (LoRR) or sedation are counted every 5 min. The data can be analyzed using three
      different statistical approaches. The first is to determine the time at which 50%
      of the flies have lost their righting reflex and use an Analysis of the Variance
      (ANOVA) to determine whether significant differences exist between time points.
      The second is to determine the percentage flies that show LoRR after a specified
      number of minutes, followed by an ANOVA analysis. The last method is to analyze
      the whole times series using multivariate statistics. The protocol can also be
      used for non-circadian experiments or comparisons between genotypes. 

PMID- 24895005
TI  - [German resuscitation registry : science and resuscitation research].
AB  - Sudden death due to cardiac arrest represents one of the greatest challenges
      facing modern medicine, not only because of the massive number of cases involved
      but also because of its tremendous social and economic impact. For many years,
      the magic figure of 1 per 1000 inhabitants per year was generally accepted as an
      estimate of the annual incidence of sudden death in the industrialized world,
      with a survival rate of 6 %. This estimate was based on large numbers of
      published reports of local, regional, national and multinational experience in
      the management of cardiac arrest. Measuring the global incidence of cardiac
      arrest is challenging as many different definitions of patient populations are
      used. Randomized controlled trials (RCT) provide insights into the value of
      specific treatments or treatment strategies in a well-defined section of a
      population. Registries do not compete with clinical studies, but represent a
      useful supplement to them. Surveys and registries provide insights into the ways
      in which scientific findings and guidelines are being implemented in clinical
      practice. However, as with clinical studies, comprehensive preparations are
      needed in order to establish a registry. This is all the more decisive because
      not all of the questions that may arise are known at the time when the registry
      is established. The German resuscitation registry started in May 2007 and
      currently more than 230 paramedic services and hospitals take part. More than
      45,000 cases of out-of-hospital cardiac arrest and in-hospital cardiac arrest are
      included. With this background the German resuscitation registry is one of the
      largest databases in emergency medicine in Germany. After 5 years of running the
      preclinical care dataset was revised in 2012. Data variables that reflect current
      or new treatment were added to the registry. The postresuscitation basic care and
      telephone cardiopulmonary resuscitation (CPR) datasets were developed in 2012 and
      2013 as well. The German resuscitation registry is an instrument of quality
      management and a research network. The registry documents the course in patients
      who have undergone resuscitation at the time points of first aid, further
      management and long-term outcome and it can therefore provide a complete
      presentation of the procedures carried out and the quality of the outcomes. In
      addition, important scientific questions can be answered from the database. For
      example, a score for benchmarking the outcome quality after out-of-hospital
      resuscitation, known as the return of spontaneous circulation (ROSC) after
      cardiac arrest (RACA) score, has been developed. The registry is available for
      all emergency medical services (EMS) and hospitals in Germany and other German
      speaking countries. 

PMID- 24895007
TI  - Ulk1-mediated Atg5-independent macroautophagy mediates elimination of
      mitochondria from embryonic reticulocytes.
AB  - Macroautophagy is a highly conserved intracellular process responsible for the
      degradation of subcellular constituents. Macroautophagy was recently suggested to
      be involved in the removal of mitochondria from reticulocytes during the final
      stage of erythrocyte differentiation. Although Atg5 and Atg7 are indispensable
      for macroautophagy, their role in mitochondrial clearance remains controversial.
      We recently discovered that mammalian cells use conventional Atg5/Atg7-dependent
      macroautophagy as well as an alternative Unc-51-like kinase 1 (Ulk1)-dependent
      Atg5/Atg7-independent macroautophagy process. We hypothesized that the latter may
      be involved in mitochondrial clearance from reticulocytes during erythrocyte
      differentiation. Here we report that fetal definitive reticulocytes from Ulk1
      deficient and Ulk1/Atg5 double-deficient mice retain their mitochondria, whereas
      the mitochondria are engulfed and digested within autophagic structures in wild
      type and Atg5-deficient mice. Mitochondrial retention by Ulk1-deficient
      reticulocytes is far less marked in primitive and adult definitive reticulocytes.
      These data indicate that Ulk1-dependent Atg5-independent macroautophagy is the
      dominant process of mitochondrial clearance from fetal definitive reticulocytes. 

PMID- 24895008
TI  - Retrospective reconstruction of cardiac cine images from golden-ratio radial MRI
      using one-dimensional navigators.
AB  - PURPOSE: To demonstrate radial golden-ratio-based cardiac cine imaging by using
      interspersed one-dimensional (1D) navigators. MATERIALS AND METHODS: The 1D
      navigators were interspersed into the acquisition of radial spokes which were
      continuously rotated by an angle increment based on the golden-ratio. Performing
      correlation analysis between the 1D navigator projections, time points
      corresponding to the same cardiac motion phases were automatically identified and
      used to combine retrospectively golden-ratio rotated radial spokes from multiple
      data windows. Data windows were shifted consecutively for dynamic reconstruction
      of different cardiac motion frames. Experiments were performed during a single
      breathhold. By artificially reducing the amount of input data, signal-to-noise
      ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifact level was
      evaluated for different breathhold durations. RESULTS: Analysis of the 1D
      navigator data provided a detailed correlation function revealing cardiac motion
      over time. Imaging results were comparable to images reconstructed based on a
      timely synchronized ECG. Cardiac cine images with a low artifact level and good
      image quality in terms of SNR and CNR were reconstructed from volunteer data
      achieving a CNR between the myocardium and the left ventricular cavity of 50 for
      the longest breathhold duration of 26 s. CNR maintained a value higher than 30
      for acquisition times as low as 10 s. CONCLUSION: Combining radial golden-ratio
      based imaging with an intrinsic navigator is a promising and robust method for
      performing high quality cardiac cine imaging.

PMID- 24895009
TI  - Analysis of global RNA synthesis at the single cell level following hypoxia.
AB  - Hypoxia or lowering of the oxygen availability is involved in many physiological
      and pathological processes. At the molecular level, cells initiate a particular
      transcriptional program in order to mount an appropriate and coordinated cellular
      response. The cell possesses several oxygen sensor enzymes that require molecular
      oxygen as cofactor for their activity. These range from prolyl-hydroxylases to
      histone demethylases. The majority of studies analyzing cellular responses to
      hypoxia are based on cellular populations and average studies, and as such single
      cell analysis of hypoxic cells are seldom performed. Here we describe a method of
      analysis of global RNA synthesis at the single cell level in hypoxia by using
      Click-iT RNA imaging kits in an oxygen controlled workstation, followed by
      microscopy analysis and quantification.  Using cancer cells exposed to hypoxia
      for different lengths of time, RNA is labeled and measured in each cell. This
      analysis allows the visualization of temporal and cell-to-cell changes in global
      RNA synthesis following hypoxic stress. 

PMID- 24895010
TI  - Essential parameters for structural analysis and dereplication by (1)H NMR
      spectroscopy.
AB  - The present study demonstrates the importance of adequate precision when
      reporting the delta and J parameters of frequency domain (1)H NMR (HNMR) data.
      Using a variety of structural classes (terpenoids, phenolics, alkaloids) from
      different taxa (plants, cyanobacteria), this study develops rationales that
      explain the importance of enhanced precision in NMR spectroscopic analysis and
      rationalizes the need for reporting Deltadelta and DeltaJ values at the 0.1-1 ppb
      and 10 mHz level, respectively. Spectral simulations paired with iteration are
      shown to be essential tools for complete spectral interpretation, adequate
      precision, and unambiguous HNMR-driven dereplication and metabolomic analysis.
      The broader applicability of the recommendation relates to the physicochemical
      properties of hydrogen ((1)H) and its ubiquity in organic molecules, making HNMR
      spectra an integral component of structure elucidation and verification.
      Regardless of origin or molecular weight, the HNMR spectrum of a compound can be
      very complex and encode a wealth of structural information that is often obscured
      by limited spectral dispersion and the occurrence of higher order effects. This
      altogether limits spectral interpretation, confines decoding of the underlying
      spin parameters, and explains the major challenge associated with the translation
      of HNMR spectra into tabulated information. On the other hand, the
      reproducibility of the spectral data set of any (new) chemical entity is
      essential for its structure elucidation and subsequent dereplication. Handling
      and documenting HNMR data with adequate precision is critical for establishing
      unequivocal links between chemical structure, analytical data, metabolomes, and
      biological activity. Using the full potential of HNMR spectra will facilitate the
      general reproducibility for future studies of bioactive chemicals, especially of
      compounds obtained from the diversity of terrestrial and marine organisms. 

PMID- 24895012
TI  - Observations on the right ovary of birds of prey: a histological and
      immunohistochemical study.
AB  - In most avian species, only the left ovary and oviduct are developed in the adult
      bird. Right ovaries and oviducts usually do not mature further after hatching and
      remain only rudimentary. However, occurrence of a functional right ovary is
      frequently found in several species of birds of prey. In this study, we
      investigated the occurrence of the right ovaries and their morphology in these
      bird species. Four examined wild bird species possessed a right ovary: long-eared
      owl, common buzzard, sparrow hawk and goshawk. We used histological and
      immunohistochemical techniques to evaluate structural differences of the gonads
      and tried to correlate the findings with folliculogenesis and endocrine
      functions. The right ovaries showed different sizes and shapes. Cytoskeletal
      elements (tubulin and vimentin) and alpha-smooth muscle actin have been detected
      in different structures of the right ovaries, but their staining intensity was
      weaker compared with the left ovary. This shows that also the right ovary is
      mechanically able to ovulate. We could also demonstrate the expression of
      oestrogen receptor alpha and progesterone receptor in the right ovaries, which
      indicates that also the right ovary can respond to steroid hormone stimuli. We
      assume that the expression of steroid hormone receptors in the presumptive gonad
      is still sufficient to mediate the development of a right ovary in the studied
      species. We conclude that the expression of steroid hormone receptors in the
      right ovary is involved in its post-natal development. The histological and
      immunohistochemical data also imply that in the right ovary, folliculogenesis and
      ovulation can occur. 

PMID- 24895011
TI  - Intricate effects of primary motor neuronopathy on contractile proteins and
      metabolic muscle enzymes as revealed by label-free mass spectrometry.
AB  - While the long-term physiological adaptation of the neuromuscular system to
      changed functional demands is usually reflected by unilateral skeletal muscle
      transitions, the progressive degeneration of distinct motor neuron populations is
      often associated with more complex changes in the abundance and/or isoform
      expression pattern of contractile proteins and metabolic enzymes. In order to
      evaluate these intricate effects of primary motor neuronopathy on the skeletal
      muscle proteome, label-free MS was employed to study global alterations in the WR
      (wobbler) mouse model of progressive neurodegeneration. In motor neuron disease,
      fibre-type specification and the metabolic weighting of bioenergetic pathways
      appear to be strongly influenced by both a differing degree of a subtype-specific
      vulnerability of neuromuscular synapses and compensatory mechanisms of fibre-type
      shifting. Proteomic profiling confirmed this pathobiochemical complexity of
      disease-induced changes and showed distinct alterations in 72 protein species,
      including a variety of fibre-type-specific isoforms of contractile proteins,
      metabolic enzymes, metabolite transporters and ion-regulatory proteins, as well
      as changes in molecular chaperones and various structural proteins. Increases in
      slow myosin light chains and the troponin complex and a decrease in fast MBP
      (myosin-binding protein) probably reflect the initial preferential loss of the
      fast type of neuromuscular synapses in motor neuron disease.

PMID- 24895013
TI  - Sponge phase producing porous CeO2 for catalytic oxidation of CO.
AB  - The aggregation behavior of mixtures of the alkaline amino acid L-Arginine (L
      Arg) and bis(2-ethylhexyl)phosphoric acid (DEHPA) in water was studied in detail.
      At a fixed L-Arg concentration, a phase sequence of micellar phase (L1 phase),
      vesicle phase (Lalphav phase), planar lamellar phase (Lalphal phase), and sponge
      phase (L3 phase) was obtained with increasing DEHPA concentration due to changes
      in the packing parameter. The phase transition of the lamellar structures was
      determined by freeze-fracture TEM and (2)H NMR spectroscopy. Rheological
      measurements reflected the phase transition through significant variations of
      both the elastic modulus and the viscous modulus. Porous CeO2 materials were
      produced by utilizing the L3 phase as template, and the porous CeO2 exhibited
      excellent catalytic oxidation activity toward CO due to its high surface area,
      which provides more active sites for CO conversion.

PMID- 24895015
TI  - Widening educational inequalities in adolescent smoking following national
      tobacco control policies in the Netherlands in 2003: a time-series analysis.
AB  - BACKGROUND AND AIMS: In 2003, the Netherlands introduced tobacco control
      policies, including bans on tobacco sales to minors, advertising and sponsoring
      and tobacco sales in government institutions. We examined the extent to which
      these policies were associated with a change in educational inequalities in
      adolescent smoking. DESIGN: Repeated cross-sectional survey. SETTING: The
      Netherlands, 1992-2011. PARTICIPANTS: A total of 43 527 14-19-year-old
      adolescents. MEASUREMENTS: Data were obtained from the national Youth Smoking
      Monitor. We used logistic regression analyses to model the immediate change in
      daily smoking prevalence in 2003, the trends and the changes in trends. Models
      included interactions between educational level (high versus low, based on the
      educational track of the respondent) and, respectively, period (after versus
      before 2003), time and time * period. FINDINGS: Before 2003 the smoking trend
      declined slightly, and the decline was comparable for students of both high and
      low educational levels. Immediately after tobacco policies were introduced, daily
      smoking prevalence dropped for the total population [regression coefficient
      (beta) = -0.340, 95% confidence interval (CI) = -0.445; -0.236]. This drop was
      larger for high educational level compared to low educational level (beta
      interaction = -0.400, 95% CI = -0.623; -0.176). After 2003, trends in educational
      inequalities in smoking stabilized. CONCLUSIONS: Following the introduction of
      new tobacco control policies in the Netherlands in 2003, smoking prevalence rates
      decreased among adolescents of both higher and lower educational levels. However,
      socio-economic inequalities in adolescent smoking increased.

PMID- 24895016
TI  - A computational mechanics approach to assess the link between cell morphology and
      forces during confined migration.
AB  - Confined migration plays a fundamental role during several biological phenomena
      such as embryogenesis, immunity and tumorogenesis. Here, we propose a two
      dimensional mechanical model to simulate the migration of a HeLa cell through a
      micro-channel. As in our previous works, the cell is modelled as a continuum and
      a standard Maxwell model is used to describe the mechanical behaviour of both the
      cytoplasm (including active strains) and the nucleus. The cell cyclically
      protrudes and contracts and develops viscous forces to adhere to the substrate.
      The micro-channel is represented by two rigid walls, and it exerts an additional
      viscous force on the cell boundaries. We test four channels whose dimensions in
      terms of width are i) larger than the cell diameter, ii) sub-cellular, ii) sub
      nuclear and iv) much smaller than the nucleus diameter. The main objective of the
      work is to assess the necessary conditions for the cell to enter into the channel
      and migrate through it. Therefore, we evaluate both the evolution of the cell
      morphology and the cell-channel and cell-substrate surface forces, and we show
      that there exists a link between the two, which is the essential parameter
      determining whether the cell is permeative, invasive or penetrating. 

PMID- 24895014
TI  - Evidence that the population of quiescent bone marrow-residing very small
      embryonic/epiblast-like stem cells (VSELs) expands in response to neurotoxic
      treatment.
AB  - The concept that bone marrow (BM)-derived cells may participate in neural
      regeneration remains controversial, and the identity of the specific cell type(s)
      involved remains unknown. We recently reported that the adult murine BM contains
      a highly mobile population of Sca-1(+) Lin(-) CD45(-) cells known as very small
      embryonic/epiblast-like stem cells (VSELs) that express several markers of
      pluripotency such as Oct-4. In the BM microenvironment, these cells are kept
      quiescent because of epigenetic modification of certain paternally imprinted
      genes. However, as reported, these cells can be mobilized in mice in an
      experimental model of stroke and express several genes involved in neurogenesis
      while circulating in peripheral blood (PB). In the current work, we employed a
      model of toxic brain damage, which is induced by administration of kainic acid,
      to see not only whether VSELs can be mobilized into PB in response to this
      neurotoxin, but, more importantly, whether they proliferate and expand in BM
      tissue. We report here for the first time that brain damage leads to activation
      and expansion of the BM pool of quiescent VSELs, which precedes their subsequent
      egress into PB. Harnessing these cells in neural tissue regeneration is currently
      one of the challenges in regenerative medicine. 

PMID- 24895017
TI  - Reflex vasovagal syncope--is there a benefit in pacemaker therapy?
AB  - Reflex vasovagal syncope often affects young populations and is associated with a
      benign prognosis in terms of mortality. However, a minority of patients have
      recurrent episodes, with a considerable impact on their quality of life.
      Pacemaker therapy has been an option in these patients since the 1990s if a
      conservative strategy fails. Initially, non-randomized and open-label randomized
      trials showed promising results, but these studies were associated with a
      significant placebo effect. Recently, an approach based on the use of implantable
      loop recorders has shown that some patients with reflex vasovagal syncope could
      benefit from implantation with dual-chamber pacemakers, particularly patients
      aged >40 years, with recurrent syncopal episodes resulting in frequent injuries,
      in whom a long asystole (>=3 s asystole with syncope or >=6 s asystole without
      syncope) has been documented with an implantable loop recorder. The authors
      present a literature review on the role of cardiac pacing in reflex vasovagal
      syncope and propose a diagnostic and therapeutic decision flowchart for patients
      with syncope of probable reflex etiology. 

PMID- 24895018
TI  - Pre-operative indicators for mortality following hip fracture surgery: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: hip fracture is a common and serious condition associated with high
      mortality. This study aimed to identify pre-operative characteristics which are
      associated with an increased risk of mortality after hip fracture surgery.
      DESIGN: systematic search of published and unpublished literature databases,
      including EMBASE, MEDLINE, AMED, CINAHL, PubMed and the Cochrane Library, was
      undertaken to identify all clinical studies on pre-operative predictors of
      mortality after surgery in hip fracture with at least 3-month follow-up. Data
      pertaining to the study objectives was extracted by two reviewers independently.
      Where study homogeneity was evidence, a meta-analysis of pooled relative risk and
      95% confidence intervals was performed for mortality against pre-admission
      characteristics. RESULTS: fifty-three studies including 544,733 participants were
      included. Thirteen characteristics were identified as possible pre-operative
      indicators for mortality. Following meta-analysis, the four key characteristics
      associated with the risk of mortality up to 12 months were abnormal ECG (RR:
      2.00; 95% CI: 1.45, 2.76), cognitive impairment (RR: 1.91; 95% CI: 1.35, 2.70),
      age >85 years (RR: 0.42; 95% CI: 0.20, 0.90) and pre-fracture mobility (RR: 0.13;
      95% CI: 0.05, 0.34). Other statistically significant pre-fracture predictors of
      increased mortality were male gender, being resident in a care institution, intra
      capsular fracture type, high ASA grade and high Charlson comorbidity score on
      admission. CONCLUSIONS: this review has identified the characteristics of
      patients with a high risk of mortality after a hip fracture surgery beyond the
      peri-operative period who may benefit from comprehensive assessment and
      appropriate management. PROSPERO REGISTRATION NUMBER: CRD42012002107.

PMID- 24895019
TI  - Haemodynamic vector personalization of a quadripolar left ventricular lead used
      for cardiac resynchronization therapy: use of surface electrocardiogram and
      interventricular time delays.
AB  - AIMS: The choice of left ventricular pacing configurations (LVPCs) of quadripolar
      leads used for cardiac resynchronization therapy (CRT) affects haemodynamic
      response and thus may be a tool for device optimization. The value of surface
      electrocardiograms and interventricular time delays (IVDs) for optimization is
      unknown. METHODS AND RESULTS: Sixteen patients implanted with a CRT device with a
      quadripolar LV lead underwent invasive testing of LV dP/dt. QRS durations at
      baseline (bl) and during biventricular pacing (biv) were measured using different
      LVPCs (total of 141 LVPCs; 8.8 per patient). Variations in QRS duration during
      biv were calculated for each patient (DeltaQRS) and, when compared with intrinsic
      QRS duration, for all LVPCs (DeltaQRSLVPC). Interventricular time delays between
      the poles of the LV lead were obtained from intracardiac electrograms. DeltaIVD
      was calculated as IVDmax - IVDmin. Parameters were correlated with LV dP/dt.
      DeltaQRS and DeltaQRSLVPC both significantly correlated with LV dP/dt (P < 0.01).
      Correlation was found for patients with ischaemic (P < 0.001) and non-ischaemic
      cardiomyopathy (P < 0.05), and for patients with bl QRS duration >168 ms (P <
      0.001), but not <168 ms (P = ns). The LVPC with shortest QRS duration also
      yielded maximal LV dP/dt in 6 of 16 patients (37.5%), and was equal or better in
      LV dP/dt in 12 of 16 patients (75%). DeltaIVD neither correlated with DeltaQRS
      nor DeltaLV dP/dt. CONCLUSION: DeltaQRS predicts the maximal value of vector
      personalization in the individual. Reductions in QRS width, but not IVDs,
      correlate with acute haemodynamic response. Intraindividually, in 75% of
      patients, the LVPC with the shortest QRS duration gives equal or superior
      haemodynamic results when compared with the LVPC with longest QRS duration.

PMID- 24895020
TI  - The adenosine triphosphate test in the diagnosis of unexplained syncope: a test
      looking for a home.

PMID- 24895021
TI  - Decline of defibrillation testing in the clinical practice: an 8-year nation-wide
      assessment.

PMID- 24895022
TI  - Near-infrared spectroscopy correlates with established histological scores in a
      miniature pig model of cartilage regeneration.
AB  - Near-Infrared Spectroscopy (NIRS) could be of clinical relevance in modern
      cartilage regeneration.In a miniature pig model correlation of measurements and
      histologic scores have never been used before. The data analysis was part of an
      animal project that investigated the effects of seeding a chondrogenic and
      osteogenic scaffold with a bone-marrow-derived cell concentrate and reports the
      histological and mechanical properties. We created 20 osteochondral defects in
      the femoral condyles of 10 miniature pigs.The defects were left empty (E), filled
      with the grafted cylinder upside down (U), or with a combined scaffold (S)
      containing a spongy bone cylinder covered with a collagen membrane. In the fourth
      group, the same scaffolds were implanted but seeded with a stem cell concentrate
      (S+BMCC). The animals were euthanized after 3 months, and histologic and
      spectrometric analyses were performed. NIRS measurements were significantly
      higher in the central area of the defects of group S+BMCC compared to the central
      area of the defects of group U. In all groups, a correlation between NIRS and the
      histologic scores could be demonstrated though on different levels. In the
      central area, a good NIRS measurement correlates with low (good) histologic
      scores. In group E and group S, this negative correlation was significant
      (p=0.01). For the first time, NIRS was successfully used to evaluate
      osteochondral constructs in a miniature pig model. 

PMID- 24895023
TI  - Chemometrics meets cytometry. Analysis of multivariate spectral data to organize
      and discriminate biological information.

PMID- 24895025
TI  - Structure-driven orientation of the high-spin-low-spin interface in a spin
      crossover single crystal.
AB  - The orientation of the high-spin (HS)-low-spin (LS) macroscopic interface at the
      thermal transition of thin [{Fe(NCSe)(py)2}2(m-bpypz)] crystals is explained by
      considering the possible vanishing of the structural mismatch between the
      coexisting phases. The structural property which allows mismatch-free interfaces
      is characterized. The observed orientations of the interface and the tilt angle
      between the HS and LS domains are accurately reproduced by a two-dimensional
      continuous medium model, based on the structural data. Simulations using an
      atomistic electro-elastic model meet the predictions of the macroscopic analysis
      and provide information on the distribution of the elastic energy density in the
      biphasic state. The presence of mismatch-free domain structures can explain the
      exceptional resilience of these crystals upon repeated switching.

PMID- 24895024
TI  - Investigation of membrane penetration depth and interactions of the amino
      terminal domain of huntingtin: refined analysis by tryptophan fluorescence
      measurement.
AB  - The membrane-association properties of the amino-terminal domain of huntingtin
      are accompanied by subcellular redistribution of the protein in cellular
      compartments. In this study we used tryptophan substitution of amino-acid
      residues at different positions of the huntingtin 1-17 domain (Htt17) to
      precisely determine, for the first time, the depth of penetration of the peptides
      within the lipid bilayer. Initially, secondary structure preferences and membrane
      association properties were quantitatively determined for several membrane lipid
      compositions; they were found to be closely related to those of the natural
      peptide, indicating that changes in the sequence had little effect on these
      characteristics of the domain. The tryptophan-substituted peptides became
      inserted into the membranes' interfacial region, with average tryptophan
      positions between 7.5 and 11 A from the bilayer center, in agreement with in
      plane orientation of the peptide. Participation of the very-amino terminus of the
      peptide in the membrane-association process was demonstrated. The results not
      only revealed the occurrence of association intermediates when the huntingtin 1
      17 anchoring sequence became inserted into the membrane but also suggest the
      formation of aggregates and/or oligomers during membrane association. When
      inserted, the F11W site was of crucial importance in lipid anchoring and
      stabilization of the whole peptide, whereas the terminal residues are located
      close to the membrane surface. The carboxy-terminal tryptophan (F17W), which also
      constitutes the site of the polyglutamine extension in the natural domain, was
      found closest to the aqueous environment, accompanied with the highest aqueous
      quenching constants. These results were used to propose a refined model of lipid
      interactions of the huntingtin 1-17 domain. 

PMID- 24895026
TI  - Synthesis of 3-acylindoles by visible-light induced intramolecular oxidative
      cyclization of o-alkynylated N,N-dialkylamines.
AB  - A visible-light photoredox synthesis of 3-acylindoles through intramolecular
      oxidative cyclization of o-alkynylated N,N-dialkylamines is developed. The
      reaction proceeds effectively under mild reaction conditions using air as the
      oxidant, and only water is generated as a side product. A plausible mechanism
      involving the addition of alpha-amino alkyl radicals to alkynes, followed by C-O
      bond formation, is proposed. 

PMID- 24895028
TI  - Divergent dynamics and the Kauzmann temperature in glass forming systems.
AB  - In the last decade the challenging analysis of previtreous behavior of relaxation
      time (tau(T)) in ultraviscous low molecular weight liquids led to the conceptual
      shift of the glass transition physics toward theories not predicting a "finite
      temperature" divergence. This "breakthrough" experimental finding was
      strengthened by the discovery that "dynamic" (i.e. from tau(T) fitting) and
      "thermodynamic" estimations of the "ideal glass" (Kauzmann) temperature do not
      match, what in fact questioned its existence. In this report, due to the novel
      way of analysis based on the transformation of tau(T) experimental data to the
      activation energy temperature index form, the clear prevalence of the "finite
      temperature" divergence is proved. The obtained "dynamic" singular temperatures
      clearly coincide with "thermodynamic" estimations of the Kauzmann temperature,
      thus solving also the second mystery. The comprehensive picture was obtained due
      to the analysis of 55 experimental data-sets, ranging from low molecular weight
      liquids and polymers to liquid crystal and plastic crystals.

PMID- 24895027
TI  - A chemical potentiator of copper-accumulation used to investigate the iron
      regulons of Saccharomyces cerevisiae.
AB  - The extreme resistance of Saccharomyces cerevisiae to copper is overcome by 2-(6
      benzyl-2-pyridyl)quinazoline (BPQ), providing a chemical-biology tool which has
      been exploited in two lines of discovery. First, BPQ is shown to form a red
      (BPQ)2 Cu(I) complex and promote Ctr1-independent copper-accumulation in whole
      cells and in mitochondria isolated from treated cells. Multiple phenotypes,
      including loss of aconitase activity, are consistent with copper-BPQ mediated
      damage to mitochondrial iron-sulphur clusters. Thus, a biochemical basis of
      copper-toxicity in S. cerevisiae is analogous to other organisms. Second, iron
      regulons controlled by Aft1/2, Cth2 and Yap5 that respond to mitochondrial iron
      sulphur cluster status are modulated by copper-BPQ causing iron hyper
      accumulation via upregulated iron-import. Comparison of copper-BPQ treated,
      untreated and copper-only treated wild-type and fra2Delta by RNA-seq has
      uncovered a new candidate Aft1 target-gene (LSO1) and paralogous non-target
      (LSO2), plus nine putative Cth2 target-transcripts. Two lines of evidence confirm
      that Fra2 dominates basal repression of the Aft1/2 regulons in iron-replete
      cultures. Fra2-independent control of these regulons is also observed but CTH2
      itself appears to be atypically Fra2-dependent. However, control of Cth2-target
      transcripts which is independent of CTH2 transcript abundance or of Fra2, is also
      quantified. Use of copper-BPQ supports a substantial contribution of metabolite
      repression to iron-regulation. 

PMID- 24895030
TI  - Variability of average SUV from several hottest voxels is lower than that of
      SUVmax and SUVpeak.
AB  - OBJECTIVES: To assess variability of the average standard uptake value (SUV)
      computed by varying the number of hottest voxels within an (18)F
      fluorodeoxyglucose ((18)F-FDG)-positive lesion. This SUV metric was compared with
      the maximal SUV (SUV(max): the hottest voxel) and peak SUV (SUV(peak): SUV(max)
      and its 26 neighbouring voxels). METHODS: Twelve lung cancer patients (20
      lesions) were analysed using PET dynamic acquisition involving ten successive 2.5
      min frames. In each frame and lesion, average SUV obtained from the N = 5, 10,
      15, 20, 25 or 30 hottest voxels (SUV(max-N)), SUV(max) and SUV(peak) were
      assessed. The relative standard deviations (SDrs) from ten frames were calculated
      for each SUV metric and lesion, yielding the mean relative SD from 20 lesions for
      each SUV metric (SDr(N), SDr(max) and SDr(peak)), and hence relative measurement
      error and repeatability (MEr-R). RESULTS: For each N, SDr(N) was significantly
      lower than SDr(max) and SDr(peak). SDr(N) correlated strongly with N: 6.471 * N(
      0.103) (r = 0.994; P < 0.01). MEr-R of SUV(max-30) was 8.94-12.63% (95% CL),
      versus 13.86-19.59% and 13.41-18.95% for SUV(max) and SUV(peak) respectively.
      CONCLUSIONS: Variability of SUV(max-N) is significantly lower than for SUV(max)
      and SUV(peak). Further prospective studies should be performed to determine the
      optimal total hottest volume, as voxel volume may depend on the PET system. KEY
      POINTS: * PET imaging provides functional parameters of (18) F-FDG-positive
      lesions, such as SUVmax and SUVpeak. * Averaging SUV from several hottest voxels
      (SUVmax-N) is a further SUV metric. * Variability of SUVmax-N is significantly
      lower than SUVmax and SUVpeak variability. * SUVmax-N should improve SUV accuracy
      for predicting outcome or assessing treatment response. * An optimal total
      hottest volume should be determined through further prospective studies.

PMID- 24895029
TI  - Optimization of the antiviral potency and lipophilicity of halogenated 2,6
      diarylpyridinamines as a novel class of HIV-1 NNRTIS.
AB  - Nineteen new halogenated diarylpyridinamine (DAPA) analogues modified at the
      phenoxy C-ring were synthesized and evaluated for anti-HIV activity and certain
      drug-like properties. Ten compounds showed high anti-HIV activity (EC50 <10 nM).
      In particular, (E)-6-(2''-bromo-4''-cyanovinyl-6''-methoxy)phenoxy-N(2) -(4'
      cyanophenyl)pyridin-2,3-diamine (8 c) displayed low-nanomolar antiviral potency
      (3-7 nM) against wild-type and drug-resistant viral strains bearing the E138K or
      K101E mutations, which are associated with resistance to rilvipirine (1 b).
      Compound 8 c exhibited much lower resistance fold changes (RFC: 1.1-2.1) than 1 b
      (RFC: 11.8-13.0). Compound 8 c also exhibited better metabolic stability (in
      vitro half-life) than 1 b in human liver microsomes, possessed low lipophilicity
      (clog D: 3.29; measured log P: 3.31), and had desirable lipophilic efficiency
      indices (LE>0.3, LLE>5, LELP<10). With balanced potency and drug-like properties,
      8 c merits further development as an anti-HIV drug candidate. 

PMID- 24895031
TI  - Dual-phase dual-energy CT in patients with lung cancer: assessment of the
      additional value of iodine quantification in lymph node therapy response.
AB  - OBJECTIVES: To investigate the potential contribution of iodine uptake
      calculation from dual-phase dual-energy CT (DE-CT) for lymph node staging and
      therapy response monitoring in lung cancer patients. METHODS: Retrospective
      analysis of 27 patients with non-small cell lung carcinoma (NSCLC), who underwent
      dual-phase DE-CT before and after chemotherapy, was performed. Iodine uptake
      (mg/mL) and total iodine uptake (mg) were calculated using prototype software in
      the early (arterial) and late (venous) post-contrast circulatory phase in 110
      mediastinal lymph nodes. The arterial enhancement fraction (AEF) was calculated
      and compared with lymph node size and response to chemotherapy. RESULTS: A
      significant difference of AEF was observed between enlarged (90.4%; 32.3-238.5%)
      and non-enlarged (72.7%; -37.5-237.5%) lymph nodes (p = 0.044) before treatment
      onset. A significantly different change of AEF in responding (decrease of 26.3%;
      p = 0.022) and non-responding (increase of 43.0%; p = 0.031) lymph nodes was
      demonstrated. A higher value of AEF before treatment was observed in lymph nodes
      with subsequent favourable response (88.6% vs. 77.7%; p = 0.122), but this
      difference did not reach statistical significance. CONCLUSIONS: The dual-phase DE
      CT examination with quantification of ratio of early and late post-contrast
      iodine uptake is a feasible and promising method for the functional evaluation of
      mediastinal lymph nodes including therapy response assessment. KEY POINTS: * Dual
      phase DE-CT is beneficial for mediastinal lymph node assessment in NSCLC. *
      Arterial to venous iodine uptake ratio was higher in enlarged lymph nodes. *
      Change of arterial enhancement fraction correlated to therapy response.

PMID- 24895032
TI  - The interaction between stent(s) implantation, PICA involvement, and immediate
      occlusion degree affect symptomatic intracranial spontaneous vertebral artery
      dissection aneurysm (sis-VADA) recurrence after reconstructive treatment with
      stent(s)-assisted coiling.
AB  - OBJECTIVES: We aimed to evaluate risk factors of sis-VADAs recurrence after
      reconstructive treatment based on 113 reconstructed lesions. METHODS: A total of
      111 patients (M:F = 68:43; median age, 47 years) with 113 sis-VADAs underwent
      reconstruction from October 2000 to March 2011, using stent(s) and coils.
      Treatments and predictors of recurrence were retrospectively analysed. RESULTS:
      Fifty-eight sis-VADAs underwent single-stent treatment, and the remaining 55 sis
      VADAs underwent treatment with 2-4 overlapping stents. Follow-up angiography was
      available for 94 sis-VADAs 12 -78 months, with recurrence in ten patients,
      including seven angiographic recurrences and three post-treatment haemorrhagic
      recurrences. A higher rate of post-treatment recurrence was observed in the
      single stent group than in the multiple stents group (p = 0.010). The interaction
      between stent (s) implantation and immediate occlusion degree (odds ratio [OR]
      =3.152; 95% confidence interval [CI], 1.293-7.686; p = 0.012), between stent (s)
      implantation and the posterior inferior cerebellar artery (PICA) involvement (OR
      = 4.607; 95% CI, 1.172-18.113; p = 0.029), and between PICA involvement and
      immediate occlusion degree (OR = 5.018; 95% CI, 1.263-19.933; p = 0.022) affect
      recurrence in the reconstructed sis-VADAs. CONCLUSIONS: This single centre cohort
      study indicated that the interaction effect between stent (s) implantation, PICA
      involvement, and immediate occlusion degree were closely associated with
      recurrence after reconstructive treatment of sis-VADA. KEY POINTS: The
      interaction between stent (s) and immediate occlusion degree affect aneurysmal
      recurrence. The interaction between stent and PICA involvement affect aneurysmal
      recurrence. The interaction between PICA involvement and immediate occlusion
      degree affect aneurysmal recurrence.

PMID- 24895033
TI  - Anomalous origin of the coronary artery from the wrong coronary sinus evaluated
      with computed tomography: "high-risk" anatomy and its clinical relevance.
AB  - OBJECTIVE: The aim of the study was to assess coronary arteries arising from the
      wrong coronary sinus, including CT-evaluated high-risk anatomic features,
      clinical symptoms and cardiac events during follow-up. METHODS: A total of 7,115
      patients scheduled for 64-slice or dual-source cardiac CT were screened for the
      presence of isolated anomalous origin of the coronary artery from the wrong
      coronary sinus. RESULTS: Anomalous origin of the coronary artery was found in 54
      (0.76 %) patients (29 men, 25 women, mean age 60.9 +/- 11.6 years). Sixteen (30
      %) patients with abnormal right coronary origin (ARCA) more commonly had a slit
      like orifice (15 vs. 3; p < 0.001), intramural course (15 vs. 3; p < 0.001) and
      interarterial course (11 vs. 0; p < 0.001) than 22 (41 %) and 13 (24 %)
      individuals with abnormal circumflex artery (ALCx) and left coronary artery
      (ALCA) origin, respectively. Patients with ALCA presented less frequently with
      chest pain than subjects with ARCA and ALCx (25 vs. 3; p = 0.03). Patients with
      ARCA tended to show higher occurrence of cardiac events in the follow-up than
      individuals with ALCA and ALCx (5 vs. 4; p = NS). CONCLUSIONS: High-risk anatomy
      features are most common in patients with ARCA and these patients also have
      higher prevalence of chest pain and cardiac events in the follow-up than
      individuals with ALCA and ALCx. KEY POINTS: * Multislice computed tomography
      enables detection and evaluation of the coronary artery anomalies. * Anomalous
      anatomy of the coronary artery potentially influences the prevalence of adverse
      events. * Adverse events tend to be most common in anomalous right coronary
      arteries.

PMID- 24895034
TI  - Radiation dose reduction in CT fluoroscopy-guided lumbar interlaminar epidural
      steroid injection by minimizing preliminary planning imaging.
AB  - OBJECTIVES: To test whether radiation dose reduction in CTF-guided LIESI would be
      achieved by replacing the preliminary planning CT with a spot CTF while still
      maintaining technical performance. METHODS: This retrospective study included a
      review of 247 consecutive procedures performed on 241 patients before (comparison
      group: n = 124) and after (study group: n = 123) instituting the above-mentioned
      the protocol modification. The patient (age, sex, body diameter, and level
      injected) and performance (procedure time, number of CTF acquisitions, and DLP)
      characteristics were compared between the two groups. RESULTS: The total DLP of
      the study group (median 4.94 mGy . cm) was significantly reduced compared to that
      of the comparison group (median 31.78 mGy . cm, P < 0.001). The numbers of CTF
      acquisitions needed for needle placement and epidurography were very similar for
      both groups (median 3, P = 0.685). The mean procedure time was significantly
      shorter for the study group (5:14 +/- 1:06 min) compared to the comparison group
      (5:53 +/- 1:19 min, P < 0.001). CONCLUSIONS: When conducting CTF-guided LIESIs, a
      significant radiation dose reduction (median 84.5% in DLP, P < 0.001) can be
      achieved by minimizing the preliminary planning examination, without compromising
      the number of CTF acquisitions and the procedure time. KEY POINTS: Majority of
      radiation is delivered during the preliminary planning image acquisition. Spot
      CTF scan can replace the preliminary planning helical examination. Patient dose
      can be reduced to as low as 0.09 mSv.

PMID- 24895036
TI  - Improvement of image quality and radiation dose of CT perfusion of the brain by
      means of low-tube voltage (70 KV).
AB  - OBJECTIVES: To investigate the feasibility of 70 kV cerebral CT perfusion by
      comparing image quality and radiation exposure to 80 kV. METHODS: Thirty patients
      with suspected cerebral ischemia who underwent dual-source CT perfusion were
      divided into group A (80 kV, 150 mAs) and group B (70 kV, 150 mAs). Quantitative
      comparisons were used for maximum enhancement, signal-to-noise index (SNI), and
      values of cerebral blood flow (CBF), cerebral blood flow (CBV), mean transit time
      (MTT) on CBF, CBV, and MTT images, and radiation dose from these two groups.
      Qualitative perfusion images were assessed by two readers. RESULTS: Maximum
      enhancement for group B was higher than group A (P < 0.05). There were no
      significant differences between the two groups for SNI on CBF and CBV maps (P =
      0.06 - 0.576), but significant differences for MTT when SNI was measured on
      frontal white matter and temporo-occipital white matter (P < 0.05). There were no
      differences among values of CBF, CBV, and MTT for both groups (P = 0.251-0.917).
      Mean image quality score in group B was higher than group A for CBF (P < 0.05),
      but no differences for CBV (P = 0.542) and MTT (P = 0.962). Radiation dose for
      group B decreased compared with group A. CONCLUSIONS: 70 kV cerebral CT perfusion
      reduces radiation dose without compromising image quality. KEY POINTS: *
      Radiation dose is a key concern with the increased using cerebral CT perfusion.
      Cerebral CT perfusion of 70 kV reduces radiation dose without compromising image
      quality. * A 70-kV protocol could be used for cerebral CT perfusion.

PMID- 24895035
TI  - Assessment of sub-clinical acute cellular rejection after heart transplantation:
      comparison of cardiac magnetic resonance imaging and endomyocardial biopsy.
AB  - OBJECTIVE: Comparing the diagnostic value of multi-sequential cardiac magnetic
      resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac
      allograft rejection. METHODS: One hundred and forty-six examinations in 73
      patients (mean age 53 +/- 12 years, 58 men) were performed using a 1.5 Tesla
      system and compared to EMB. Examinations included a STIR (short tau inversion
      recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo
      sequence for assessment of global relative enhancement (gRE), and inversion
      recovery sequences to visualize late gadolinium enhancement (LGE). Histological
      grade >=1B was considered relevant rejection. RESULTS: One hundred and twenty
      seven (127/146 = 87 %) EMBs demonstrated no or mild signs of rejection (grades
      <=1A) and 19/146 (13 %) a relevant rejection (grade >=1B). Sensitivity,
      specificity, positive predictive, and negative predictive values were as follows:
      ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %,
      13 %, and 87 %; with the combination of ER and gRE with at least one out of two
      positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the
      curve of 0.724 for ER and 0.659 for gRE. CONCLUSION: CMR parameters for
      myocarditis are useful to detect sub-clinical acute cellular rejection after
      heart transplantation. Comparable results to myocarditis can be achieved with a
      combination of parameters. KEY POINTS: * Magnetic resonance imaging is useful for
      the assessment of cardiac allograft rejection. * CMR has a high negative
      predictive value for exclusion of allograft rejection. * Diagnostic performance
      is not yet good enough to replace endomyocardial biopsy.

PMID- 24895037
TI  - CT and MR imaging of multilocular acinar cell cystadenoma: comparison with branch
      duct intraductal papillary mucinous neoplasia (IPMNs).
AB  - OBJECTIVES: To describe CT and MR imaging findings of acinar cell cystadenoma
      (ACC) of the pancreas and to compare them with those of branch duct intraductal
      papillary mucinous neoplasia (BD-IPMN) to identify distinctive elements. METHODS:
      Five patients with ACC and the 20 consecutive patients with histologically proven
      BD-IPMN were retrospectively included. Clinical and biological information was
      collected and histological data reviewed. CT and MR findings were analysed
      blinded to pathological diagnosis in order to identify imaging diagnostic
      criteria of ACC. RESULTS: Patients with ACC were symptomatic in all but one case
      and were younger than those with BD-IPMN (p = 0.006). Four radiological criteria
      allowed for differentiating ACC from IPMN: five or more cysts, clustered
      peripheral small cysts, presence of cyst calcifications and absence of
      communication with the main pancreatic duct (p < 0.05). Presence of at least two
      or three of these imaging criteria had a strong diagnostic value for ACC with a
      sensitivity of 100% and 80% and a specificity of 85% and 100%, respectively.
      CONCLUSIONS: Preoperative differential diagnosis between ACC and BD-IPMN can be
      achieved using a combination of four CT and/or MR imaging criteria. Recognition
      of ACC patients could change patient management and lead to more conservative
      treatment. KEY POINTS: Four imaging findings are associated with acinar cell
      cystadenoma (ACC). Imaging could achieve differential diagnosis between ACC and
      BD-IPMN. Diagnosis on imaging would change patient management and avoid surgical
      resection.

PMID- 24895038
TI  - US-guided high-intensity focused ultrasound as a promising non-invasive method
      for treatment of primary hyperparathyroidism.
AB  - OBJECTIVES: To investigate the long-term efficacy and safety of ultrasound (US)
      guided high-intensity focused ultrasound (HIFU) treatment in patients with
      primary hyperparathyroidism (PHPT). METHODS: In our prospective study, 13 of 72
      screened patients with PHPT were eligible for HIFU treatment, which was performed
      in one or two sessions. Parathyroid adenoma size and function were evaluated at
      baseline, 1, 3, 6, 9, and 12 months after the final HIFU session. RESULTS: In 11
      females and 2 males, mean age 55.2 +/- 12.41 years, the mean applied energy was
      15.2 +/- 7.7 kJ. Parathyroid size and parathyroid hormone decreased significantly
      one month after HIFU therapy (p < 0.002 and p < 0.02, respectively). Calcium
      concentration decreased slowly to reach significant reduction nine months later
      (p < 0.05). Complete remission was noted in three patients (23%) after one year,
      good disease control was achieved in nine (69%), and procedure was unsuccessful
      in one patient (8%). Number of sessions was significantly related to treatment
      success (p < 0.05). Transitory side effects were impaired vocal cord mobility in
      three patients (23.1%), subcutaneous oedema in three patients (23.1%), and a
      combination of both in two patients (15.4%). CONCLUSIONS: HIFU is a promising non
      invasive technique for PHPT treatment, which could serve as therapeutic
      alternative for selected patients. KEY POINTS: US-guided HIFU is a new non
      invasive ablative technique for parathyroid adenomas. The method is efficient and
      ensures good disease control in most patients. HIFU is a good alternative for
      patients not meeting surgery criteria. Treatment is well-tolerated with only
      transient side effects.

PMID- 24895039
TI  - MRI displays involvement of the temporalis muscle and the deep temporal artery in
      patients with giant cell arteritis.
AB  - PURPOSE: To assess deep temporal artery and temporalis muscle involvement in
      patients with giant cell arteritis (GCA). MATERIAL AND METHODS: Ninety-nine
      patients who received magnetic resonance imaging (MRI) and superficial temporal
      artery biopsy (TAB) were included in this study. Patients with positive TAB (n =
      61) were defined as GCA patients, those with negative TAB (n = 38) as the GCA
      negative reference group. Contrast-enhanced T1w-images were acquired utilizing
      1.5 T and 3 T MRI. Two radiologists assessed the images. Mural contrast
      hyperenhancement and wall thickening of the deep temporal artery and
      hyperenhancement of the muscle were defined as inflammation. MRI results were
      correlated with jaw claudication in 70 patients. RESULTS: The two observers found
      temporalis muscle involvement in 19.7 % (n = 12) and 21.3 % (n = 13) of GCA
      patients. It occurred bilaterally in 100 %. Specificities were 92/97 % and
      sensitivities were 20/21 %. Deep temporal artery involvement was found in 34.4 %
      (n = 21) and 49.2 % (n = 30) and occurred bilaterally in 80/90.5 %. Specificities
      were 84/95 % and sensitivities were 34/49 %. Both structures were affected
      simultaneously in 18/21.3 %. Jaw claudication correlated moderately with
      inflammation of the temporalis muscle (r = 0.31; p < 0.05) and the deep temporal
      artery (r = 0.38; p = 0.01). CONCLUSION: MRI visualizes changes in the temporalis
      muscle and the deep temporal artery in GCA. Moderate correlation of clinical
      symptoms with MRI results was observed. KEY POINTS: * Approximately 20 % of GCA
      patients presented with temporalis muscle inflammation. * A total of 34-49 % of
      GCA patients presented with vasculitis of the deep temporal artery. * In
      approximately 20 % of GCA patients, both structures were simultaneously involved.
      * Involvement of both structures correlated moderately with presence of jaw
      claudication. * MRI is a suitable tool for the assessment of vasculitis and
      muscle inflammation.

PMID- 24895040
TI  - Tumour volume doubling time of molecular breast cancer subtypes assessed by
      serial breast ultrasound.
AB  - OBJECTIVES: The aim of our study was to evaluate the tumour volume doubling time
      (TVDT) of molecular breast cancer subtypes by serial ultrasound (US). METHODS:
      Sixty-six patients (mean age, 50 years; range, 29-78 years) with invasive breast
      cancer underwent initial and follow-up breast US examinations (at least three
      months apart) with no intervention. TVDT was determined using the tumours'
      greatest dimensions in two orthogonal planes. The results were compared with
      clinical, imaging, and tumour variables and molecular subtypes (oestrogen
      receptor [ER]-positive, human epidermal growth factor receptor 2 [HER2]-positive,
      and triple negative) using a multiple linear regression analysis. RESULTS: TVDT
      exhibited a wide range (46-825 days; median, 141 days) with an overall mean of
      193 +/- 141 days and mean values of 241 +/- 166 days for ER-positive tumours (n =
      37), 162 +/- 60 days for HER2-positive tumours (n = 12), and 103 +/- 43 days for
      triple-negative tumours (n = 17) (P < 0.0001). In a multivariate regression
      analysis, compared to other features, only the different molecular breast cancer
      subtypes showed significant difference in TVDT (P < 0.0001). CONCLUSIONS: TVDT
      differed significantly among the three molecular breast cancer subtypes, with the
      triple-negative tumours showing the fastest growth. KEY POINTS: Knowledge of
      tumour volume doubling time provides clues for improving screening. TVDT assessed
      by serial US differed significantly between breast cancer subtypes. Triple
      negative tumours had 2.4-fold shorter TVDT compared to ER-positive tumours.
      Tumours classified as BI-RADS 3 had shorter TVDT than BI-RADS 4.

PMID- 24895041
TI  - Pulmonary nodules and masses in lung transplant recipients: clinical and CT
      findings.
AB  - OBJECTIVES: The purpose of this study was to review the clinical and CT findings
      of pulmonary nodules and masses in lung transplant recipients and to determine
      distinguishing features among the various aetiologies. METHODS: This
      retrospective study included 106 lung transplant recipients who had a chest CT
      performed over a 7-year period in a single institution. RESULTS: Twenty-four
      cases of pulmonary nodules and masses were observed on CT. Among the single
      lesions, three (50%) were due to infections, one (17%) to organizing pneumonia,
      and two (33%) remained of undetermined origin. Among the multiple lesions, 14
      (78%) were due to infection, three to post-transplant lymphoproliferative
      disorder (17%), and one to bronchogenic carcinoma (5%). The two main
      microorganisms were P. aeruginosa and Aspergillus spp. Among 12 solid nodules > 1
      cm, four (33%) were due to malignancy: three post-transplant lymphoproliferative
      disorders (25%), and one bronchogenic carcinoma (8%). Among five cavitary nodules
      four (80%) were due to aspergillosis. CONCLUSION: Infection is the most frequent
      aetiology of pulmonary nodules and masses in lung transplant recipients, but
      other causes such as post-transplant lymphoproliferative disorder, bronchogenic
      carcinoma, or organizing pneumonia should be considered. KEY POINTS: Pulmonary
      nodules and masses are frequent in lung transplant recipients. Infection is the
      most frequent aetiology of solitary and multiple pulmonary nodules. Differential
      diagnosis includes post-transplant lymphoproliferative disorder, bronchogenic
      carcinoma, and organizing pneumonia. Clinical and CT findings are often non
      specific. CT findings may be suggestive of some aetiologies that justify a
      biopsy.

PMID- 24895042
TI  - Clinical implication of fasting and post-challenged plasma glucose in diagnosis
      of diabetes mellitus.
AB  - Fasting plasma glucose (FPG) is the preferred test in diagnosis of diabetes
      mellitus (DM) to 2-h post-challenged plasma glucose (2hPG). There is little
      information available on the comparison between FPG and 2hPG diagnostic criteria.
      This study included adult participants (>=18 years old) of the NHANES 2005-2010
      with FPG, 2hPG, and BMI measured. Subjects with established DM were excluded. The
      sensitivity of FPG and 2hPG diagnostic criteria was compared as the main outcome
      measure. Among 5,782 subjects, 476 subjects (8.23 %) were diagnosed with DM by
      either FPG, 2hPG, or both criteria. Among the subjects meeting the criterion of
      FPG, those with 2hPG <200 mg/dL were younger (57 +/- 16 vs. 61 +/- 15 years old,
      P < 0.05, mean +/- STD) and less obese (30.81 +/- 7.89 vs. 32.71 +/- 6.68
      kg/m(2), P < 0.05) as compared to those with 2hPG >=200 mg/dL. Among the subjects
      meeting the criterion of 2hPG, those with FPG <126 mg/dL were more female (55.41
      vs. 39.88 %, P < 0.0002), less obese (29.24 +/- 5.83 vs. 32.71 +/- 6.68 kg/m(2),
      P < 0.000001), lower diastolic blood pressure (67 +/- 12 vs. 71 +/- 14 mmHg, P <
      0.02), and less family history of DM (36.35 vs. 48.47 %, P < 0.02) as compared to
      those with FPG >=126 mg/dL. The sensitivity of diagnosis of DM was only 41.37 %
      for FPG criterion, while it was 66.53 % for 2hPG criterion. Thus, compared to
      2hPG criterion, FPG criterion had a lower sensitivity detecting new cases of DM.
      The use of FPG criterion would more likely result in underdiagnosing DM,
      especially in female and less obese subjects, as compared to the use of 2hPG
      criterion.

PMID- 24895043
TI  - Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet
      fed rat.
AB  - Our previous study has demonstrated that long-term stress, known as chronic
      stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet
      (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic
      pathways were impacted by CS in the HFD-fed rat. Male Sprague-Dawley rats (6
      weeks of age, n = 8 per group) were fed with either standard diet or HFD with or
      without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and
      lipid profile markers in serum and liver, and enzymes involved in de novo
      lipogenesis (DNL) of fatty acids (FAs) and cholesterol, beta-oxidation, FAs
      uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly
      in the liver were detected. CS exposure reduced hepatic lipidosis but further
      elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats.
      There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR
      and western blot assays showed that CS exposure significantly promoted hepatic
      VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact
      on DNL, beta-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed
      rats. This phenomenon was in accordance with elevated serum glucocorticoid level.
      The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed
      rats is VLDL assembly which might be regulated by glucocorticoid.

PMID- 24895045
TI  - Comments on 'Graphical assessment of internal and external calibration of
      logistic regression models by using loess smoothers' by Peter C. Austin and Ewout
      W. Steyerberg.

PMID- 24895044
TI  - Fibroblast growth factor 21 expressions in white blood cells and sera of patients
      with gestational diabetes mellitus during gestation and postpartum.
AB  - Fibroblast growth factor 21 (FGF21), a recently discovered regulatory factor,
      plays an important role in glucose and lipid metabolism. In this study, we
      firstly found the FGF21 expression in white blood cells (WBCs). Then, we enrolled
      51 women with gestational diabetes mellitus (GDM) and 50 pregnant women with
      normal blood glucose levels to determine the FGF21 levels in the WBCs and the
      sera at the 28th week of pregnancy, and tracked the dynamic changes of FGF21 in
      these women until the 7th day postpartum. Repeated Measures analysis of variance
      (ANOVA) revealed that there was a significant interaction effect between group
      and time on FGF21 levels (P < 0.05). FGF21 levels were significantly higher in
      the GDM patients than those in the controls at the 28th week of pregnancy. The
      7th day after the delivery, the FGF21 levels decreased in the WBCs and the sera
      in both groups. The D values (the difference between pregnancy and postpartum)
      for FGF21 levels were significantly higher in the GDM group (P < 0.05). Serum
      FGF21 level during gestation positively correlated with leptin, triglyceride, and
      HDL-cholesterol, and FGF21 may act as a glucose and lipid metabolism compensatory
      regulatory factor to improve glucose and lipid metabolism during the period of
      pregnancy. Further, FGF21 level in the WBCs (during pregnancy and the D values
      for FGF21) was chiefly influenced by GDM. 

PMID- 24895046
TI  - Bootstrap confidence intervals for loess-based calibration curves.

PMID- 24895047
TI  - Sociocultural Influences on Weight-Related Behaviors in African American
      Adolescents.
AB  - The purpose of this study was to examine the sociocultural factors related to
      weight behaviors in African American adolescents utilizing a social ecological
      approach. A descriptive correlational design included a sample of 145 African
      American adolescents. Perceived familial socialization, ethnic identity, physical
      activity, and eating behavior patterns were measured. Data were analyzed using
      descriptive statistics, Pearson product-moment correlations, and multiple
      regression equations. Perceived maternal socialization was significantly related
      to adolescent eating behaviors and physical activity whereas perceived paternal
      socialization was significantly related only to their physical activity. The
      adolescents' ethnic identity was not significantly related to their eating
      behaviors or physical activity. Health care providers who work with adolescents
      and their families can use the initial findings from this study to encourage
      healthy weight-related behaviors while reducing the obesity epidemic within the
      African American adolescent population in a developmentally appropriate and
      culturally sensitive manner. 

PMID- 24895048
TI  - The Quality, Implementation, and Evaluation Model: A Clinical Practice Model for
      Sustainable Interventions.
AB  - Major efforts have been directed toward the implementation of sustainable quality
      improvement. To date, progress has been noted using various metrics and
      performance measures; however, successful implementation has proven challenging.
      The Quality, Implementation, and Evaluation (QIE) model, derived from
      Donabedian's structure component, presents a framework for implementation of
      specific activities. The QIE model consists of Policy, Patient Preparedness,
      Provider Competency, and Performance and Accountability, to guide specific
      practice initiatives. The implementation of alcohol-based pre-operative skin prep
      was evaluated in a sample of 17 hospitals and demonstrated that hospitals
      actively engaged in the components of the model demonstrated a significantly
      higher use of alcohol-based skin preparation agent than hospitals that did not
      engage in QIE model activities. The QIE model presents a powerful and actionable
      implementation model for mid-level management and clinical leadership. Future
      studies will further evaluate the impact of the specific components of the QIE
      model.

PMID- 24895049
TI  - Slum residence and child health in developing countries.
AB  - Continued population growth and increasing urbanization have led to the formation
      of large informal urban settlements in many developing countries in recent
      decades. The high prevalence of poverty, overcrowding, and poor sanitation
      observed in these settlements-commonly referred to as "slums"-suggests that slum
      residence constitutes a major health risk for children. In this article, we use
      data from 191 Demographic and Health Surveys (DHS) across 73 developing countries
      to investigate this concern empirically. Our results indicate that children in
      slums have better health outcomes than children living in rural areas yet fare
      worse than children in better-off neighborhoods of the same urban settlements. A
      large fraction of the observed health differences appears to be explained by
      pronounced differences in maternal education, household wealth, and access to
      health services across residential areas. After we control for these
      characteristics, children growing up in the slums and better-off neighborhoods of
      towns show levels of morbidity and mortality that are not statistically different
      from those of children living in rural areas. Compared with rural children,
      children living in cities (irrespective of slum or formal residence) fare better
      with respect to mortality and stunting but not with respect to recent illness
      episodes. 

PMID- 24895050
TI  - Chemical composition of Enterococcus faecalis in biofilm cells initiated from
      different physiologic states.
AB  - Enterococcus faecalis is a ubiquitous bacterium of the gut that is observed in
      persistent periradicular infections. Its pathogenicity is associated with biofilm
      formation and the ability to survive under nutrient-poor (starvation) conditions.
      However, characteristics of chemical composition of biofilm cells developed by
      starved E. faecalis cells remain poorly understood. In this study, E. faecalis
      cells in exponential, stationary, and starvation phases were prepared and
      separately cultured to form biofilms. Confocal laser scanning microscopy was
      performed to verify biofilm formation. Raman microscopy was used to investigate
      the chemical composition of cells within the biofilms. Compared to cells in
      exponential or stationary phase, starved cells developed biofilms with fewer
      culturable cells (P < 0.05). Raman analysis revealed that cells produced in the
      biofilms from starved planktonic cells contained more protein and less nucleic
      acids than either the corresponding planktonic cells or the cells in biofilms
      from planktonic cells in exponential or stationary phases, suggesting that
      biofilm-grown cells from the starvation phase were characterized by increased
      synthesis of proteins and decreased nucleic acids. This study provides an insight
      into the chemical composition of biofilm cells developed by starved E. faecalis.

PMID- 24895051
TI  - Tracking in vivo dynamics of NK cells transferred in patients undergoing stem
      cell transplantation.
AB  - Haploidentical stem cell transplantation (haploSCT) offers an alternative
      treatment option for advanced leukemia patients lacking a HLA-compatible donor.
      Transfer of NK cells represents a promising therapeutic option in combination
      with SCT, as NK cells can promote graft versus leukemia with low risk of GVH
      disease. In this study, we show results from a phase I/II trial in which 24 acute
      myeloid leukemia patients underwent haploSCT in combination with early transfer
      of unmodified NK cells and observed a promising 2-year overall survival rate of
      37%. By performing immunomonitoring and subsequent principal component analysis,
      we tracked donor NK-cell dynamics in the patients and distinguished between NK
      cells reconstituting from CD34(+) precursors, giving rise over time to a
      continuum of multiple differentiation stages, and adoptively transferred NK
      cells. Transferred NK cells displayed a mature phenotype and proliferated in vivo
      during the early days after haploSCT even in the absence of exogenous IL-2
      administration. Moreover, we identified the NK-cell phenotype associated with in
      vivo expansion. Thus, our study indicates a promising path for adoptive transfer
      of unmodified NK cells in the treatment of high-risk acute myeloid leukemia. 

PMID- 24895052
TI  - Focusing of sub-micrometer particles and bacteria enabled by two-dimensional
      acoustophoresis.
AB  - Handling of sub-micrometer bioparticles such as bacteria are becoming
      increasingly important in the biomedical field and in environmental and food
      analysis. As a result, there is an increased need for less labor-intensive and
      time-consuming handling methods. Here, an acoustophoresis-based microfluidic chip
      that uses ultrasound to focus sub-micrometer particles and bacteria, is
      presented. The ability to focus sub-micrometer bioparticles in a standing one
      dimensional acoustic wave is generally limited by the acoustic-streaming-induced
      drag force, which becomes increasingly significant the smaller the particles are.
      By using two-dimensional acoustic focusing, i.e. focusing of the sub-micrometer
      particles both horizontally and vertically in the cross section of a
      microchannel, the acoustic streaming velocity field can be altered to allow
      focusing. Here, the focusability of E. coli and polystyrene particles as small as
      0.5 MUm in diameter in microchannels of square or rectangular cross sections, is
      demonstrated. Numerical analysis was used to determine generic transverse
      particle trajectories in the channels, which revealed spiral-shaped trajectories
      of the sub-micrometer particles towards the center of the microchannel; this was
      also confirmed by experimental observations. The ability to focus and enrich
      bacteria and other sub-micrometer bioparticles using acoustophoresis opens the
      research field to new microbiological applications. 

PMID- 24895053
TI  - Prevalence and clinical characteristics of active epilepsy in southern Han
      Chinese.
AB  - PURPOSE: To investigate the prevalence and clinical characteristics of active
      epilepsy in southern Han Chinese. METHOD: A door-to-door survey about epilepsy
      was conducted in communities identified by random cluster sampling among 20
      villages and 3 communities of Yueyang city. A questionnaire for epilepsy based on
      the World Health Organization screening questionnaire was used. A final diagnosis
      of epilepsy was made by neurology specialists with the support of head magnetic
      resonance imaging (MRI), computed tomography (CT), and electroencephalography
      (EEG) if available. The prevalence, clinical characteristics, and treatment gap
      were analyzed in patients with active epilepsy within the past year and the past
      5 years. RESULTS: Active epilepsy was identified in 91 patients within the past
      year and 117 patients within the past 5 years. The one-year prevalence was
      2.80/00, and the five-year prevalence was 3.70/00. The prevalence for epilepsy
      active within the last year and the last five years was significantly higher in
      rural areas than in urban areas (P<0.05). Secondary generalized tonic-clonic
      seizures (53.8%) were the most common seizure type in patients whose epilepsy had
      been active in the last year. 34.1% of patients were diagnosed with structural or
      metabolic epilepsy. The most common cause for epilepsy was cerebrovascular
      disease (32.3%), followed by traumatic brain injury (29.0%). The treatment gap
      was 93.4%. CONCLUSION: The prevalence of epilepsy active within the last one and
      five years was higher in rural areas than in urban areas of Yueyang city. A large
      treatment gap exists in this area and a rational intervention strategy is needed.

PMID- 24895055
TI  - Dicke-type phase transition in a spin-orbit-coupled Bose-Einstein condensate.
AB  - Spin-orbit-coupled Bose-Einstein condensates (BECs) provide a powerful tool to
      investigate interesting gauge field-related phenomena. Here we study the ground
      state properties of such a system and show that it can be mapped to the well
      known Dicke model in quantum optics, which describes the interactions between an
      ensemble of atoms and an optical field. A central prediction of the Dicke model
      is a quantum phase transition between a superradiant phase and a normal phase. We
      detect this transition in a spin-orbit-coupled BEC by measuring various physical
      quantities across the phase transition. These quantities include the spin
      polarization, the relative occupation of the nearly degenerate single-particle
      states, the quantity analogous to the photon field occupation and the period of a
      collective oscillation (quadrupole mode). The applicability of the Dicke model to
      spin-orbit-coupled BECs may lead to interesting applications in quantum optics
      and quantum information science. 

PMID- 24895054
TI  - Isolation, culture, and imaging of human fetal pancreatic cell clusters.
AB  - For almost 30 years, scientists have demonstrated that human fetal ICCs
      transplanted under the kidney capsule of nude mice matured into functioning
      endocrine cells, as evidenced by a significant increase in circulating human C
      peptide following glucose stimulation(1-9). However in vitro, genesis of insulin
      producing cells from human fetal ICCs is low(10); results reminiscent of recent
      experiments performed with human embryonic stem cells (hESC), a renewable source
      of cells that hold great promise as a potential therapeutic treatment for type 1
      diabetes. Like ICCs, transplantation of partially differentiated hESC generate
      glucose responsive, insulin producing cells, but in vitro genesis of insulin
      producing cells from hESC is much less robust(11-17). A complete understanding of
      the factors that influence the growth and differentiation of endocrine precursor
      cells will likely require data generated from both ICCs and hESC. While a number
      of protocols exist to generate insulin producing cells from hESC in vitro(11-22),
      far fewer exist for ICCs(10,23,24). Part of that discrepancy likely comes from
      the difficulty of working with human fetal pancreas. Towards that end, we have
      continued to build upon existing methods to isolate fetal islets from human
      pancreases with gestational ages ranging from 12 to 23 weeks, grow the cells as a
      monolayer or in suspension, and image for cell proliferation, pancreatic markers
      and human hormones including glucagon and C-peptide. ICCs generated by the
      protocol described below result in C-peptide release after transplantation under
      the kidney capsule of nude mice that are similar to C-peptide levels obtained by
      transplantation of fresh tissue(6). Although the examples presented here focus
      upon the pancreatic endoderm proliferation and beta cell genesis, the protocol
      can be employed to study other aspects of pancreatic development, including
      exocrine, ductal, and other hormone producing cells.

PMID- 24895056
TI  - Targeted delivery of miRNA therapeutics for cardiovascular diseases:
      opportunities and challenges.
AB  - Dysregulation of miRNA expression has been associated with many cardiovascular
      diseases in animal models, as well as in patients. In the present review, we
      summarize recent findings on the role of miRNAs in cardiovascular diseases and
      discuss the opportunities, possibilities and challenges of using miRNAs as future
      therapeutic targets. Furthermore, we focus on the different approaches that can
      be used to deliver these newly developed miRNA therapeutics to their sites of
      action. Since siRNAs are structurally homologous with the miRNA therapeutics,
      important lessons learned from siRNA delivery strategies are discussed that might
      be applicable to targeted delivery of miRNA therapeutics, thereby reducing costs
      and potential side effects, and improving efficacy.

PMID- 24895058
TI  - NICE issues draft guidance on preventing and treating acute kidney injury.

PMID- 24895059
TI  - Anatomical and immunohistochemical characteristics of the prostate gland in the
      greater cane rat (Thryonomys swinderianus).
AB  - This study examined the morphology and immunohistochemical features of the
      prostate gland in 15 captive-reared male greater cane rat of known reproductive
      and medical history. Samples of the glands were taken after gross examination and
      routinely prepared for both histological and ultrastructural analysis.
      Immunohistochemistry was also carried out on paraffin-embedded sections of the
      glands using rabbit polyclonal antibodies against oestrogen receptors (ERalpha
      and ERbeta) and mouse monoclonal antibody for the progesterone receptor (PR). The
      prostate, which constitutes 0.04% of the body weight, was a paired, lobulated,
      brownish gland having three left and four right lobes that partly cover the
      pelvic urethra. Based on the amount and arrangement of the secretory epithelial
      folding and relative to their distances to the urethra, two histological zones,
      the central and peripheral, were identified. However, the epithelium of both
      zones was lined by predominantly simple cuboidal cells with occasional basal
      cells. The main ultrastructural features of these cuboidal cells were the
      presence of several nuclear pores on the nucleus, moderately well-developed,
      short microvilli and bleb-like apical projections, as well as inter-cellular
      lacunae seen between these cells and the basal cells. The cuboidal epithelial
      cells also showed positive nuclear staining for ERalpha and ERbeta but not for
      PR. It is however interesting that the ERalpha-positive staining was more at the
      epithelial cells, which is uncommon. These findings highlight the peculiarities
      in the structure and ultrastructure as well as the unique expression of the
      oestrogen receptors in the prostate gland of the greater cane rat. 

PMID- 24895057
TI  - The Bioenergetic Health Index: a new concept in mitochondrial translational
      research.
AB  - Bioenergetics has become central to our understanding of pathological mechanisms,
      the development of new therapeutic strategies and as a biomarker for disease
      progression in neurodegeneration, diabetes, cancer and cardiovascular disease. A
      key concept is that the mitochondrion can act as the 'canary in the coal mine' by
      serving as an early warning of bioenergetic crisis in patient populations. We
      propose that new clinical tests to monitor changes in bioenergetics in patient
      populations are needed to take advantage of the early and sensitive ability of
      bioenergetics to determine severity and progression in complex and multifactorial
      diseases. With the recent development of high-throughput assays to measure
      cellular energetic function in the small number of cells that can be isolated
      from human blood these clinical tests are now feasible. We have shown that the
      sequential addition of well-characterized inhibitors of oxidative phosphorylation
      allows a bioenergetic profile to be measured in cells isolated from normal or
      pathological samples. From these data we propose that a single value-the
      Bioenergetic Health Index (BHI)-can be calculated to represent the patient's
      composite mitochondrial profile for a selected cell type. In the present
      Hypothesis paper, we discuss how BHI could serve as a dynamic index of
      bioenergetic health and how it can be measured in platelets and leucocytes. We
      propose that, ultimately, BHI has the potential to be a new biomarker for
      assessing patient health with both prognostic and diagnostic value.

PMID- 24895060
TI  - Neutral nickel ethylene oligo- and polymerization catalysts: towards
      computational catalyst prediction and design.
AB  - DFT calculations have been used to elucidate the chain termination mechanisms for
      neutral nickel ethylene oligo- and polymerization catalysts and to rationalize
      the kind of oligomers and polymers produced by each catalyst. The catalysts
      studied are the (kappa(2)-O,O)-coordinated (1,1,1,5,5,5-hexafluoro-2,4
      acetylacetonato)nickel catalyst I, the (kappa(2)-P,O)-coordinated SHOP-type
      nickel catalyst II, the (kappa(2)-N,O)-coordinated anilinotropone and
      salicylaldiminato nickel catalysts III and IV, respectively, and the (kappa(2)
      P,N)-coordinated phosphinosulfonamide nickel catalyst V. Numerous termination
      pathways involving beta-H elimination and beta-H transfer steps have been
      investigated, and the most probable routes identified. Despite the complexity and
      multitude of the possible termination pathways, the information most critical to
      chain termination is contained in only few transition states. In addition, by
      consideration of the propagation pathway, we have been able to estimate chain
      lengths and discriminate between oligo- and polymerization catalysts. In
      agreement with experiment, we found the Gibbs free energy difference between the
      overall barrier for the most facile propagation and termination pathways to be
      close to 0 kcal mol(-1) for the ethylene oligomerization catalysts I and V,
      whereas values of at least 7 kcal mol(-1) in favor of propagation were determined
      for the polymerization catalysts III and IV. Because of the shared intermediates
      between the termination and branching pathways, we have been able to identify the
      preferred cis/trans regiochemistry of beta-H elimination and show that a
      pronounced difference in sigma donation of the two bridgehead atoms of the
      bidentate ligand can suppress hydride formation and thus branching. The degree of
      rationalization obtained here from a handful of key intermediates and transition
      states is promising for the use of computational methods in the screening and
      prediction of new catalysts of the title class.

PMID- 24895061
TI  - HBP1 promoter methylation augments the oncogenic beta-catenin to correlate with
      prognosis in NSCLC.
AB  - beta-catenin nuclear accumulation is frequently identified in human non-small
      cell lung cancer (NSCLC). The HMG-box transcription factor 1 (HBP1) is a known
      repressor of beta-catenin transactivation. However, the role of HBP1 in relation
      to beta-catenin nuclear accumulation has not been addressed in human cancer
      patients. In addition, the mechanism of HBP1 gene alteration in NSCLC remains
      unclear, although HBP1 mutation and gene deletion of HBP1 are reported in breast
      and colon cancers. Here, we demonstrate that HBP1 acts as a tumour suppressor and
      serves as a prognostic biomarker in NSCLC clinical and cell models. The
      immunohistochemistry data indicated that 30.5% (25/82) of tumours from NSCLC
      patients showed absence or low expression of HBP1 protein. A significant inverse
      correlation between mRNA/protein expression and promoter hypermethylation
      suggested that promoter hypermethylation is responsible for low expression of
      HBP1 in NSCLC patients. Reactivation of HBP1 expression by demethylation reagent
      or ectopic expression of HBP1 suppressed beta-catenin transactivation.
      Conversely, HBP1 knockdown increased beta-catenin transactivation. Importantly,
      preserved expression of HBP1 had a significantly protective effect on prognosis
      in patients with beta-catenin nuclear accumulation, suggesting that low
      expression of HBP1 in NSCLC patients with beta-catenin nuclear accumulation was
      one of the major determinants of prognosis. Our data from cellular and clinical
      models suggest that HBP1 is a suppressor of cancer progression, making it a
      potential prognostic predictor and therapeutic target to attenuate lung cancer
      progression. 

PMID- 24895063
TI  - Recalling the past: probation officers work with drug misusers during the 1960s.
AB  - AIMS: Britain's first wave of non-therapeutic drug users during the 1960s were
      more likely to come into contact with the criminal courts than previous,
      therapeutic, drug users. This paper recounts the untold history of probation
      officers' work with drug misusing offenders in the United Kingdom during the
      1960s. METHODS: Using 'snowballing' to source participants (in which study
      subjects recruit future subjects from among their acquaintances) and in-depth
      interviews as a means of eliciting information, probation officers who had
      supervised drug users during this time were interviewed about their experiences.
      Interviews were transcribed verbatim and a thematic data set produced. RESULTS:
      Front-line probation officers in the United Kingdom in the 1960s had considerable
      contact with drug-misusing offenders. In explaining drug addiction, officers
      tended to draw upon a psychotherapeutic interpretation, and in terms of
      intervention they relied heavily upon the psychiatric services to deliver
      treatment. Probation officers did not always make the connection between
      addiction and an increase in criminality. CONCLUSION: In Britain's first wave of
      non-therapeutic drug users in the 1960s, probation officers appear not to have
      made a connection with criminality, which may have limited how far they developed
      a formalized approach to applying the expertise of the Probation Service.

PMID- 24895062
TI  - The pharmacokinetic profile, tolerability and safety of the iodinated, non-ionic,
      dimeric contrast medium Iosimenol 340 injection in healthy human subjects.
AB  - BACKGROUND: Iosimenol 340 injection is a new isotonic iodinated contrast medium
      for X-ray angiography. PURPOSE: To investigate the pharmacokinetics and
      biotransformation, tolerability, and safety of Iosimenol 340 in healthy human
      subjects. MATERIAL AND METHODS: Twenty-four subjects were enrolled and randomized
      to receive either Iosimenol 340 (0.5, 1.5 or 3.0 mL/kg) or placebo (0.9% saline).
      In each dosing group, six subjects received Iosimenol 340 and two subjects
      received placebo. Safety was assessed by physical examination, vital signs,
      electrocardiography, and laboratory tests. Adverse events were recorded
      throughout the study up to 14 days after dosing. Blood samples were collected
      from 10 min before until 48 h after the start of dosing and urine samples were
      collected from 15 min before until 96 h after the start of dosing. Iosimenol was
      quantified in plasma and urine by measuring iodine concentrations with X-ray
      fluorescence. High-performance liquid chromatography was used to assess iosimenol
      biotransformation. RESULTS: Mean half-lives (mean +/- standard deviation [SD]) of
      iosimenol were 0.17 +/- 0.08 h (10.2 +/- 4.8 min) and 2.01 +/- 0.32 h for
      distribution and terminal elimination phases, respectively. The apparent volume
      of distribution was 0.27 +/- 0.05 L/kg, indicating distribution to the
      extracellular fluid volume. Iosimenol was excreted within 24 h without any sign
      of metabolic transformation. Thirty-two adverse events were observed in 14
      subjects. All were mild or moderate, and were transient in nature. CONCLUSION:
      Iosimenol was not metabolized, had a distribution volume corresponding to the
      extracellular space, and was rapidly excreted through the kidneys by glomerular
      filtration. The area under the plasma concentration curve and the peak plasma
      concentration was proportional to dose, while clearance was independent of dose.
      Iosimenol 340 was well tolerated.

PMID- 24895064
TI  - Automatic cardiac segmentation using semantic information from random forests.
AB  - We propose a fully automated method for segmenting the cardiac right ventricle
      (RV) from magnetic resonance (MR) images. Given a MR test image, it is first
      oversegmented into superpixels and each superpixel is analyzed to detect the
      presence of RV regions using random forest (RF) classifiers. The superpixels
      containing RV regions constitute the region of interest (ROI) which is used to
      segment the actual RV. Probability maps are generated for each ROI pixel using a
      second set of RF classifiers which give the probabilities of each pixel belonging
      to RV or background. The negative log-likelihood of these maps are used as
      penalty costs in a graph cut segmentation framework. Low-level features like
      intensity statistics, texture anisotropy and curvature asymmetry, and high level
      context features are used at different stages. Smoothness constraints are imposed
      based on semantic information (importance of each feature to the classification
      task) derived from the second set of learned RF classifiers. Experimental results
      show that compared to conventional method our algorithm achieves superior
      performance due to the inclusion of semantic knowledge and context information. 

PMID- 24895065
TI  - Midterm results of a femoral stem with a modular neck design: clinical outcomes
      and metal ion analysis.
AB  - Modular neck femoral stems have a higher-than-anticipated rate of failure in
      registry results, but large single-center cohort studies are lacking. This is a
      retrospective cohort of 152 hips implanted with a single titanium stem with a
      modular titanium neck, presenting clinical, radiographic, and metal ion results
      at a mean 4.5-year follow-up. Five hips were revised during the study period, for
      an overall Kaplan-Meier survival of 0.894 at 8 years. There was one modular neck
      fracture (0.66%), but others demonstrated corrosion or adverse tissue reaction.
      Serum metal levels demonstrated wide variability. Despite good clinical results
      in the majority of patients, we confirmed an increased rate of femoral revision
      at mid-term follow-up, and therefore urge caution in the use of this particular
      stem design.

PMID- 24895067
TI  - Sulfur-functionalized graphene oxide by epoxide ring-opening.
AB  - The treatment of graphene oxide (GO) with potassium thioacetate followed by an
      aqueous work-up yields a new material via the ring-opening of the epoxide groups.
      The new material is a thiol-functionalized GO (GO-SH) which is able to undergo
      further functionalization. Reaction with butyl bromide gives another new
      material, GO-SBu, which shows significantly enhanced thermal stability compared
      to both GO and GO-SH. The thiol-functionalized GO material showed a high affinity
      for gold, as demonstrated by the selective deposition of a high density of gold
      nanoparticles. 

PMID- 24895066
TI  - Effects of sodium acetate buffer on chitosan sponge properties and in vivo
      degradation in a rat intramuscular model.
AB  - Chitosan sponges were developed for adjunctive local antibiotic delivery to
      reduce bacteria in wounds. There is a need to increase sponge degradation for
      rapid clearance from the wound site during initial wound care. This work examined
      the effect of using 0.25 M sodium acetate buffers, at pH 4.6 or 5.6, to fabricate
      sponges with an amorphous chitosan polymer structure. Sponges were evaluated for
      their crystallinity, thermal, spectroscopic, and morphological properties, in
      addition to in vitro degradation, and cytocompatibility analysis using normal
      human dermal fibroblasts. In vivo degradation and biocompatibility were also
      examined after 4 and 10 days in rat intramuscular tissues. Both buffered chitosan
      sponge variations exhibited decreases in crystallinity and thermal decomposition
      temperatures, and increases in surface roughness, which resulted in over 40%
      increases in degradation over 10 days in vitro compared to the neutral sponges.
      There were no significant differences between sponges during in vivo degradation
      over 10 days with respect to histomorphometric analysis of the recovered sponges.
      These results demonstrated that the acetate buffer did change characteristic
      chitosan sponge material properties, and increasing the in vivo sponge
      degradation rate will require balancing material characteristics and processing.

PMID- 24895068
TI  - A fast entry to furanoditerpenoid-based Hedgehog signaling inhibitors:
      identifying essential structural features.
AB  - New, small molecule Hedgehog (Hh) pathway inhibitors, such as the
      furanoditerpenoid taepeenin D, are of high medicinal importance. To establish key
      structure-activity relationships (SARs) for this lead, a synthetic sequence has
      been developed for the expedient preparation of several derivatives and their
      evaluation as Hh inhibitors exploiting its structural similarity to abietic acid.
      While C(14) substitution is not essential for biological activity, the presence
      of a hydrogen bond acceptor at C(6) and an intact benzofuran moiety are. 

PMID- 24895069
TI  - Synthesis, sigma receptor affinity, and pharmacological evaluation of 5
      phenylsulfanyl- and 5-benzyl-substituted tetrahydro-2-benzazepines.
AB  - In accordance with a novel strategy for generating the 2-benzazepine scaffold by
      connecting C6-C1 and C3-N building blocks, a set of 5-phenylsulfanyl- and 5
      benzyl-substituted tetrahydro-2-benzazepines was synthesized and
      pharmacologically evaluated. Key steps of the synthesis were the Heck reaction,
      the Stetter reaction, a reductive cyclization, and the introduction of diverse N
      substituents at the end of the synthesis. High sigma1 affinity was achieved for 2
      benzazepines with linear or branched alk(en)yl residues containing at least an n
      butyl substructure. The butyl- and 4-fluorobenzyl-substituted derivatives, (+/-)
      5-benzyl-2-butyl-2,3,4,5-tetrahydro-1H-2-benzazepine (19 b) and (+/-)-5-benzyl-2
      (4-fluorobenzyl)-2,3,4,5-tetrahydro-1H-2-benzazepine (19 m), show high
      selectivity over more than 50 other relevant targets, including the sigma2
      subtype and various binding sites of the N-methyl-D-aspartate (NMDA) receptor. In
      the Irwin screen, 19 b and 19 m showed clean profiles without inducing
      considerable side effects. Compounds 19 b and 19 m did not reveal significant
      analgesic and cognition-enhancing activity. Compound 19 m did not have any
      antidepressant-like effects in mice. 

PMID- 24895070
TI  - A novel high-speed production process to create modular components for the bottom
      up assembly of large-scale tissue-engineered constructs.
AB  - To replace damaged or diseased tissues, large tissue-engineered constructs can be
      prepared by assembling modular components in a bottom-up approach. However, a
      high-speed method is needed to produce sufficient numbers of these modules for
      full-sized tissue substitutes. To this end, a novel production technique is
      devised, combining air shearing and a plug flow reactor-style design to rapidly
      produce large quantities of hydrogel-based (here type I collagen) cylindrical
      modular components with tunable diameters and length. Using this technique,
      modules containing NIH 3T3 cells show greater than 95% viability while
      endothelial cell surface attachment and confluent monolayer formation are
      demonstrated. Additionally, the rapidly produced modules are used to assemble
      large tissue constructs (>1 cm(3) ) in vitro. Module building blocks containing
      luciferase-expressing L929 cells are packed in full size adult rat-liver-shaped
      bioreactors and perfused with cell medium, to demonstrate the capacity to build
      organ-shaped constructs; bioluminescence demonstrates sustained viability over 3
      d. Cardiomyocyte-embedded modules are also used to assemble electrically
      stimulatable contractile tissue. 

PMID- 24895071
TI  - Immersion-related deaths in infants and children: autopsy experience from a
      specialist center.
AB  - PURPOSE: To investigate the demographics, circumstances and autopsy findings in
      infants and children dying following immersion. METHODS: A retrospective review
      of a pediatric autopsy database at a specialist center over a 16-year period
      (1995-2010) was undertaken to identify deaths between 7 days and 16 years of age
      in whom death occurred following immersion. RESULTS: 28 infants and children died
      following immersion during the study period. 82 % were aged <4 years, with peak
      age of death between 1 and 2 years. Immersion occurred at home in a bath or
      private pool in 70 % of cases. There was a lack of direct supervision in all but
      two cases where the information was recorded (91 %); one of these cases occurred
      in a public swimming lesson, and in the other the carer was incapacitated.
      Autopsy findings were non-specific. Facial or subconjunctival petechial
      hemorrhages were a feature of 18 % of cases. There was increased lung weight, or
      histological pulmonary edema/intra-alveolar hemorrhage in all but one case.
      CONCLUSIONS: The data suggest that the majority of pediatric immersion-related
      deaths were potentially preventable with appropriate supervision. The findings
      strongly support the role of education regarding adequate carer supervision of
      infants and children while bathing, particularly in children with underlying
      conditions such as epilepsy. As private pools and "hot tubs" become more common
      in the UK and other jurisdictions, specific recommendations such as fencing pools
      will need to be included in advice to carers. So-called 'dry drowning" appears to
      be an uncommon mechanism of death in this age group.

PMID- 24895072
TI  - An evaluation of two conducted electrical weapons using a swine comparative
      cardiac safety model.
AB  - Arrest-related deaths proximate to the use of a conducted electrical weapon (CEW)
      continue to generate controversy despite a better understanding of the multi
      factorial nature of many of these deaths. With the rapid adoption of this
      technology by law enforcement, and the proliferation of companies entering the
      marketplace, it is important to have a method to assess the relative safety of
      these weapons. We had previously developed a model to assess the relative cardiac
      safety of CEWs. In this study, we use this model to compare the TASER X2 and the
      Karbon Arms MPID. Our results suggest that the TASER X2 may have an improved
      cardiac safety margin over the Karbon Arms MPID as determined by a smaller area
      of cardiac pacing on the anterior chest in our model. This model seems to offer a
      reproducible means of comparing the cardiac effects of CEWs. 

PMID- 24895074
TI  - Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in a
      patient presenting with papilledema.

PMID- 24895073
TI  - Clustering of trend data using joinpoint regression models.
AB  - In this paper, we propose methods to cluster groups of two-dimensional data whose
      mean functions are piecewise linear into several clusters with common
      characteristics such as the same slopes. To fit segmented line regression models
      with common features for each possible cluster, we use a restricted least squares
      method. In implementing the restricted least squares method, we estimate the
      maximum number of segments in each cluster by using both the permutation test
      method and the Bayes information criterion method and then propose to use the
      Bayes information criterion to determine the number of clusters. For a more
      effective implementation of the clustering algorithm, we propose a measure of the
      minimum distance worth detecting and illustrate its use in two examples. We
      summarize simulation results to study properties of the proposed methods and also
      prove the consistency of the cluster grouping estimated with a given number of
      clusters. The presentation and examples in this paper focus on the segmented line
      regression model with the ordered values of the independent variable, which has
      been the model of interest in cancer trend analysis, but the proposed method can
      be applied to a general model with design points either ordered or unordered.

PMID- 24895076
TI  - The melanogenesis-inhibitory effect and the percutaneous formulation of
      ginsenoside Rb1.
AB  - Ginsenoside Rb1 (Rb1) is the most predominant ginsenoside isolated from the roots
      of ginseng (Panax ginseng C. A. Meyer). This compound is active in various human
      biological pathways that are involved in human collagen synthesis and inhibition
      of cell apoptosis. In this study, the skin-whitening effects of Rb1 were
      investigated in B16 melanoma cells. Our results showed that Rb1 inhibited
      melanogenesis in alpha-melanocyte-stimulating hormone (alpha-MSH)-stimulated B16
      cells in a dose-dependent manner, which collectively indicated that Rb1 may have
      skin-whitening effects and may be formulated into skin-whitening products for
      skin care. Accordingly, a ginsenoside collagen transdermal patch was developed as
      a vehicle to topically deliver Rb1 into pig skin. The percutaneous permeation,
      retention within skin, and release in vitro of Rb1 from seven transdermal patch
      formulas were studied. It was determined that the best formula for ginsenoside
      collagen transdermal patch is made of protein collagen hydrolysate powder (PCHP)
      2.0% (w/w), methyl cellulose (MC) 0.5% (w/w), polyethyleneglycol 6000 (PEG6000)
      0.5% (w/w), ginsenoside 0.036% (w/w), azone 0.4% (v/w), menthol 0.20% (w/w), and
      water. 

PMID- 24895075
TI  - Novel dexamethasone-loaded nanomicelles for the intermediate and posterior
      segment uveitis.
AB  - Development and characterization of dexamethasone (DEX)-encapsulated polymeric
      nanomicelles have been reported. A low molecular weight di-block copolymer was
      synthesized and characterized for its structure, molecular weights, critical
      micelle concentration (CMC), and cytotoxicity in ocular cells. In order to
      delineate the effects of drug-polymer interactions on drug solubilization in
      micelle core, a response surface methodology was generated with the help of SAS
      9.02 (exploratory model). The method for preparing micelle was modified based on
      the results obtained from exploratory model. The formulation was optimized by
      response surface methodology (optimization model) to achieve DEX solubility of
      above 1 mg/mL. The optimized formulation was characterized for DEX solubility,
      nanomicelle size, polydispersity index, surface morphology, in vitro transport
      across conjunctival cell line, and ex vivo transport across excised rabbit
      sclera. Nanomicelles exhibited average sizes in range of 25-30 nm with unimodel
      size distribution and low polydispersity of 0.125. Nanomicelles increased DEX
      permeability by 2 times across conjunctival cell line and by 2.5 times across the
      excised rabbit sclera as compared to DEX suspension. A design of experiment (DOE)
      strategy was successfully applied to understand the effects of drug-polymer
      interaction on drug solubility. DOE was also employed to achieve optimal
      formulation with high DEX solubility. Nanomicellar formulation significantly
      enhanced DEX permeability across the excised rabbit sclera. Therefore,
      nanomicellar formulation may provide therapeutic levels in the back of the eye
      following topical administration. 

PMID- 24895077
TI  - Vancomycin-eluting niosomes: a new approach to the inhibition of staphylococcal
      biofilm on abiotic surfaces.
AB  - A new vancomycin (VCM)-eluting mixed bilayer niosome formulation was evaluated
      for the control of staphylococcal colonization and biofilm formation on abiotic
      surfaces, a niosome application not explored to date. Cosurfactant niosomes were
      prepared using a Span 60/Tween 40/cholesterol blend (1: 1: 2). Tween 40, a
      polyethoxylated amphiphile, was included to enhance VCM entrapment and confer
      niosomal surface properties precluding bacterial adhesion. VCM-eluting niosomes
      showed good quality attributes including relatively high entrapment efficiency
      (~50%), association of Tween 40 with vesicles in a constant proportion (~87%),
      biphasic release profile suitable for inhibiting early bacterial colonization,
      and long-term stability at 4 degrees C for a 12-month study period. Niosomes
      significantly enhanced VCM activity against planktonic bacteria of nine
      staphylococcal strains. Using microtiter plates as abiotic surface, VCM-eluting
      niosomes proved superior to VCM in inhibiting biofilm formation, eradicating
      surface-borne biofilms, inhibiting biofilm growth, and interfering with biofilm
      induction by VCM subminimal inhibitory concentrations. Data suggest dual
      functionality of cosurfactant VCM-eluting niosomes as passive colonization
      inhibiting barrier and active antimicrobial-controlled delivery system, two
      functions recognized in infection control of abiotic surfaces and medical
      devices. 

PMID- 24895078
TI  - Prednisone has no effect on the pharmacokinetics of CYP3A4 metabolized drugs -
      midazolam and odanacatib.
AB  - We evaluated the effect of prednisone on midazolam and odanacatib
      pharmacokinetics. In this open-label, 2-period crossover study in healthy male
      subjects, midazolam 2 mg was administered (Day -1) followed by odanacatib 50 mg
      (Day 1) during Part 1. In Period 2, prednisone 10 mg once daily (qd) was
      administered on Days 1-28; odanacatib was co-administered on Day 14 and midazolam
      2 mg was co-administered on Days 1 and 28. Subjects were administered midazolam 2
      mg on Days 42 and 56. Safety and tolerability were assessed throughout the study.
      A physiologically-based pharmacokinetic (PBPK) model was also built. There were
      15 subjects enrolled; mean age was 31 years. The odanacatib AUC(0- infinity) GMR
      (90% CI) [odanacatib + prednisone (Day 14, Period 2)/odanacatib alone (Day 1,
      Period 1] was 1.06 (0.96, 1.17). AUC(0-infinity) GMR (90%CI) [midazolam +
      prednisone (Day 28, Period 2)/midazolam alone (Day -1, Period 1] was 1.08
      (0.93,1.26). There were no serious AEs or AEs leading to discontinuation. PBPK
      modeling showed that prednisone does not cause significant effects on the
      exposure of sensitive CYP3A4 substrates in vivo at therapeutic doses. Co
      administration of prednisone 10 mg qd had no effect on pharmacokinetics of either
      odanacatib 10 mg or midazolam 2 mg.

PMID- 24895079
TI  - The effects of 3D channel geometry on CTC passing pressure--towards deformability
      based cancer cell separation.
AB  - Various lab on a chip devices have been developed recently to detect and separate
      circulating tumour cells (CTCs) for early stage cancer detection. Because CTCs
      are extremely rare in the blood, next generation CTC microfilters aim at
      significant improvement in both efficiency and throughput. CTC microfilters based
      on cell deformability seem to be a promising direction. In the present research,
      we study a CTC passing event through a micro-filtering channel with various 3D
      geometries. The pressure signatures for different types of cells passing through
      different channels are characterized numerically. Specifically, five kinds of
      cross-sections, circular, square, triangular and two kinds of rectangular
      channels with aspect ratios of 2 and 5, are studied in this work. The total
      pressures for cells passing through the channels are calculated and reveal
      different behaviour from what is predicted by the static surface tension model.
      Among all five cross-sections studied, the circular cross-section features the
      highest critical pressure and thus is most suitable for high efficiency CTC
      separation. The square filtering channel provides the second largest critical
      pressure, and the triangular cross-section provides the least critical pressure
      among these three cross-sections. All these three cross-sections are better than
      the rectangular channels with aspect ratios of 2 and 5. For the rectangular
      channel, a high aspect ratio channel may lead to cell splitting at high speed,
      which will result in a periodic pressure signature. Our findings will provide
      valuable information for the design of next generation CTC microfilters. 

PMID- 24895080
TI  - Assessment methods for solid waste management: A literature review.
AB  - Assessment methods are common tools to support decisions regarding waste
      management. The objective of this review article is to provide guidance for the
      selection of appropriate evaluation methods. For this purpose, frequently used
      assessment methods are reviewed, categorised, and summarised. In total, 151
      studies have been considered in view of their goals, methodologies, systems
      investigated, and results regarding economic, environmental, and social issues. A
      goal shared by all studies is the support of stakeholders. Most studies are based
      on life cycle assessments, multi-criteria-decision-making, cost-benefit analysis,
      risk assessments, and benchmarking. Approximately 40% of the reviewed articles
      are life cycle assessment-based; and more than 50% apply scenario analysis to
      identify the best waste management options. Most studies focus on municipal solid
      waste and consider specific environmental loadings. Economic aspects are
      considered by approximately 50% of the studies, and only a small number evaluate
      social aspects. The choice of system elements and boundaries varies significantly
      among the studies; thus, assessment results are sometimes contradictory. Based on
      the results of this review, we recommend the following considerations when
      assessing waste management systems: (i) a mass balance approach based on a rigid
      input-output analysis of the entire system, (ii) a goal-oriented evaluation of
      the results of the mass balance, which takes into account the intended waste
      management objectives; and (iii) a transparent and reproducible presentation of
      the methodology, data, and results. 

PMID- 24895081
TI  - Reduction of ST-elevation myocardial infarction in Canton Ticino (Switzerland)
      after smoking bans in enclosed public places--No Smoke Pub Study.
AB  - BACKGROUND: Second-hand smoke increases the risk of acute myocardial infarction.
      Canton Ticino (CT) first introduced a smoking ban in public places in 2007. This
      offered the opportunity to assess the long-term impact of a smoking ban on the
      incidence of ST-elevation myocardial infarctions (STEMI) compared with a
      population where the law was not yet implemented. METHODS: We assessed the
      incidence of STEMI hospitalizations per 100 000 inhabitants both during 3 years
      before and after the ban application in CT and in Canton Basel City (CBC), where
      this law was not yet applied. Data were obtained from the codified hospital
      registry (ICD-10 codes). RESULTS: In CT, the mean incidence of STEMI admissions
      during the 3 pre-ban years (123.7) was significantly higher than the incidence of
      admissions in each of the 3 post-ban years (92.9, 101.6 and 89.6 respectively; P
      <.024). Analysing population subsets, a post-ban reduction was observed among
      >=65-year-old people of both sexes in each of the 3 post-ban years and in the <65
      year age group during the first post-ban year (P = 0.02). Conversely, the mean
      incidence of STEMI hospitalizations in CBC (92.4) didn't change significantly in
      each of the 3 post-ban years (83.9, 83.3 and 79.5, P = NS) during the same
      period. However, a significant long-term reduction in STEMI admissions was
      observed in CBC among the male group with >=65 years (P < 0.01). CONCLUSION: Our
      work suggests a significant impact of the smoke-free policy on the number of
      annual STEMI. Specific population subsets (i.e. >=65-year-old females) were
      particularly affected by the smoking ban, showing a significant reduction in
      STEMI hospitalizations.

PMID- 24895082
TI  - Parental leave and increased physical activity of fathers and mothers--results
      from the Northern Swedish Cohort.
AB  - BACKGROUND: Physical activity is an important public health issue. Factors shown
      to be associated with physical activity are parenthood and country-level gender
      equality, while the importance of individual gender equality (in parenthood or in
      general) remains to explore. In Scandinavia, where parental leave can be shared
      equally between mothers and fathers, parental leave is one dimension of gender
      equality in parenthood. The aim of this study was to investigate parental leave
      in relation to increased physical activity among men and women. METHODS:
      Participants in the Northern Swedish Cohort with a child born 1993-2005 (n = 584)
      were investigated with questionnaires at ages 21 and 42; register data on
      parental leave between ages 28 and 42 were obtained from Statistics Sweden. The
      relationships between parental leave between ages 28 and 42 and meeting WHO
      guidelines for physical activity at age 42, as well as changes in physical
      activity between ages 21 and 42, were tested with multinomial regression,
      controlling for socio-economic status and birth year of the child. RESULTS: For
      women, the length of parental leave was not associated with increased physical
      activity or with meeting WHO guidelines at age 42. For men, parental leave was
      associated with increased physical activity, controlling for socio-economic
      status and age of the child, but not with meeting WHO guidelines for physical
      activity at age 42. CONCLUSIONS: A gender non-traditional out-take of parental
      leave might be associated with an increase in physical activity among men at the
      lower end of the physical activity spectrum, but not among women.

PMID- 24895083
TI  - Wideband optical detector of ultrasound for medical imaging applications.
AB  - Optical sensors of ultrasound are a promising alternative to piezoelectric
      techniques, as has been recently demonstrated in the field of optoacoustic
      imaging. In medical applications, one of the major limitations of optical sensing
      technology is its susceptibility to environmental conditions, e.g. changes in
      pressure and temperature, which may saturate the detection. Additionally, the
      clinical environment often imposes stringent limits on the size and robustness of
      the sensor. In this work, the combination of pulse interferometry and fiber-based
      optical sensing is demonstrated for ultrasound detection. Pulse interferometry
      enables robust performance of the readout system in the presence of rapid
      variations in the environmental conditions, whereas the use of all-fiber
      technology leads to a mechanically flexible sensing element compatible with
      highly demanding medical applications such as intravascular imaging. In order to
      achieve a short sensor length, a pi-phase-shifted fiber Bragg grating is used,
      which acts as a resonator trapping light over an effective length of 350 um. To
      enable high bandwidth, the sensor is used for sideway detection of ultrasound,
      which is highly beneficial in circumferential imaging geometries such as
      intravascular imaging. An optoacoustic imaging setup is used to determine the
      response of the sensor for acoustic point sources at different positions.

PMID- 24895085
TI  - Medical care and organisation at the 2012 Roskilde Music Festival: a prospective
      observational study.
AB  - BACKGROUND: Music festivals, with a mix of music, alcohol and camping at the
      festival site combined with low hygiene, have become an integral part of society
      and attracts large numbers of guests. Our study was performed in order to
      increase the very limited knowledge on health-care issues and organisation of
      major music festivals. METHOD: Pre-defined illness and injury categories were
      constructed based on categories previously reported from music festivals. We
      prospectively recorded patient presentations to the Medical Health Care
      Organisation (MHCO) at the 2012 Roskilde Festival. RESULTS: During 10 days, more
      than 130,000 guests and volunteers attended the 2012 Roskilde Festival. Ten
      thousand six hundred thirty patient presentations were registered between the
      30th of June and 9th of July 2012 by the MHCO. The majority of patient
      presentations, 6919, could be handled by first-aid volunteers with different
      levels of training. The remaining 3473 patient presentations were assessed to
      require further health-care competencies or additional resources such as
      prescriptions, medication or suturing. Two hundred thirty-eight patient
      presentations were triaged to a designated observation area. Two hundred sixty
      patients were referred to a local hospital, a general practitioner or a dentist.
      The overall patient presentation rate was 72/1000 attendees, and the transport-to
      hospital rate was 1.8/1000 attendees. CONCLUSION: Our study demonstrates that
      illnesses and injuries are frequent, although mostly minor, in this normally low
      risk population consisting of primarily young and healthy guests. However,
      comparison with other recent events was difficult as only limited data have been
      published from other music festivals. Future festivals should publish similar
      data.

PMID- 24895086
TI  - Veterinary analgesia: moving closer to Nirvana?

PMID- 24895084
TI  - The effects of taxing sugar-sweetened beverages across different income groups.
AB  - This paper investigates the impact of sugar-sweetened beverages (SSB) taxes on
      consumption, bodyweight and tax burden for low-income, middle-income and high
      income groups using an Almost Ideal Demand System and 2011 Household level
      scanner data. A significant contribution of our paper is that we compare two
      types of SSB taxes recently advocated by policy makers: A 20% flat rate sales
      (valoric) tax and a 20 cent/L volumetric tax. Censored demand is accounted for
      using a two-step procedure. We find that the volumetric tax would result in a
      greater per capita weight loss than the valoric tax (0.41 kg vs. 0.29 kg). The
      difference between the change in weight is substantial for the target group of
      heavy purchasers of SSBs in low-income households, with a weight reduction of up
      to 3.20 kg for the volumetric and 2.06 kg for the valoric tax. The average yearly
      per capita tax burden on low-income households is $17.87 (0.21% of income)
      compared with $15.17 for high-income households (0.07% of income) for the valoric
      tax, and $13.80 (0.15%) and $10.10 (0.04%) for the volumetric tax. Thus, the tax
      burden is lower, and weight reduction is higher under a volumetric tax.

PMID- 24895087
TI  - Harderian gland in Canadian ostrich (Struthio camelus): a morphological and
      histochemical study.
AB  - Heads of ten healthy adult ostrich obtained from slaughter house were the
      constituted materials of the study. The Harderian gland (HG) was dissected out,
      and all of the gross morphometrical parameters including length, width and
      thickness as well as weight of left and right glands were recorded. Tissue
      sections were stained, using haematoxylin and eosin, Masson trichrome, periodic
      acid-Schiff and Alcian blue (pH 2.5) techniques. In ostrich, HG was an orbital
      organ located ventromedially around the posterior part of the eyeball. It was an
      oval flatted shape, light pink colour with irregular outline and was pointed in
      the dorsal end. Its mean length was 35.30 +/- 2.84 mm and 35.55 +/- 3.58 mm in
      left and right sides, respectively, and mean width 15.30 +/- 1.20 mm and 15.65 +/
      1.18 mm in left and right sides, respectively. There was no significant
      difference between length, thickness, weight and width of left and right glands.
      Histological results showed that the glandular epithelium was multilobular and
      compound tubuloalveolar. The gland was surrounded by a connective tissue capsule,
      and the epithelium was lined by simple columnar epithelial cells of varying
      height. The secretion of HG was mucous and the secretion type was apocrine.
      Mucosubstance analysis revealed that secretory units contained acidic and neutral
      glycoproteins. The granules within the epithelial cells lining the intralobular
      and inter-lobular excretory ducts of the gland were positive for periodic acid
      Schiff and Alcian blue (pH 2.5). 

PMID- 24895089
TI  - Fine-tuning dual emission and aggregation-induced emission switching in NPI
      BODIPY dyads.
AB  - Three new NPI-BODIPY dyads 1-3 (NPI = 1,8-naphthalimide, BODIPY = boron
      dipyrromethene) were synthesized, characterized, and studied. The NPI and BODIPY
      moieties in these dyads are electronically separated by oxoaryl bridges, and the
      compounds only differ structurally with respect to methyl substituents on the
      BODIPY fluorophore. The NPI and BODIPY moieties retain their optical features in
      molecular dyads 1-3. Dyads 1-3 show dual emission in solution originating from
      the two separate fluorescent units. The variations of the dual emission in these
      compounds are controlled by the structural flexibilities of the systems. Dyads 1
      3, depending on their molecular flexibilities, show considerably different
      spectral shapes and dissimilar intensity ratios of the two emission bands. The
      dyads also show significant aggregation-induced emission switching (AIES) on
      formation of nano-aggregates in THF/H2O with changes in emission color from green
      to red. Whereas the flexible and aggregation-prone compound 1 shows AIES, rigid
      systems with less favorable intermolecular interactions (i.e., 2 and 3) show
      aggregation-induced quenching of emission. Correlations of the emission intensity
      and structural flexibility were found to be reversed in solution and aggregated
      states. Photophysical and structural investigations suggested that intermolecular
      interactions (e.g., pi-pi stacking) play a major role in controlling the emission
      of these compounds in the aggregated state.

PMID- 24895088
TI  - Phenological response to climate change in China: a meta-analysis.
AB  - The change in the phenology of plants or animals reflects the response of living
      systems to climate change. Numerous studies have reported a consistent earlier
      spring phenophases in many parts of middle and high latitudes reflecting
      increasing temperatures with the exception of China. A systematic analysis of
      Chinese phenological response could complement the assessment of climate change
      impact for the whole Northern Hemisphere. Here, we analyze 1263 phenological time
      series (1960-2011, with 20+ years data) of 112 species extracted from 48 studies
      across 145 sites in China. Taxonomic groups include trees, shrubs, herbs, birds,
      amphibians and insects. Results demonstrate that 90.8% of the spring/summer
      phenophases time series show earlier trends and 69.0% of the autumn phenophases
      records show later trends. For spring/summer phenophases, the mean advance across
      all the taxonomic groups was 2.75 days decade(-1) ranging between 2.11 and 6.11
      days decade(-1) for insects and amphibians, respectively. Herbs and amphibians
      show significantly stronger advancement than trees, shrubs and insect. The
      response of phenophases of different taxonomic groups in autumn is more complex:
      trees, shrubs, herbs and insects show a delay between 1.93 and 4.84 days decade(
      1), while other groups reveal an advancement ranging from 1.10 to 2.11 days
      decade(-1) . For woody plants (including trees and shrubs), the stronger shifts
      toward earlier spring/summer were detected from the data series starting from
      more recent decades (1980s-2000s). The geographic factors (latitude, longitude
      and altitude) could only explain 9% and 3% of the overall variance in
      spring/summer and autumn phenological trends, respectively. The rate of change in
      spring/summer phenophase of woody plants (1960s-2000s) generally matches measured
      local warming across 49 sites in China (R=-0.33, P<0.05).

PMID- 24895093
TI  - Platelet indices are novel predictors of hospital mortality in intensive care
      unit patients.
AB  - BACKGROUND AND OBJECTIVE: Platelet volume indices (PVIs) are inexpensive and
      readily available in intensive care units (ICUs). However, their association with
      mortality has never been investigated in a critical care setting. Our study aimed
      to investigate the association of PVI and mortality in unselected ICU patients.
      METHODS: This was a retrospective study conducted in a mixed 24-bed ICU from
      September 2010 to December 2012. Platelet indices including mean platelet volume
      (MPV), platelet distribution width (PDW), platelet count, and plateletcrit were
      measured on ICU entry. Univariable analyses were performed to screen for
      variables that were associated with mortality. Variables with P < .1 were
      incorporated into a regression model to adjust for the odds ratio of platelet
      indices. RESULTS: A total of 1556 patients were included during the study period,
      including 1113 survivors and 443 nonsurvivors (mortality rate: 28.47%). Platelet
      distribution width and MPV were significantly higher in nonsurvivors than in
      survivors. Platelet distribution width greater than 17% and MPV greater than 11.3
      fL were independent risk factors for mortality (adjusted odds ratio: 1.92 and
      1.84, respectively) and survival time (hazards ratio: 1.77 and 1.75,
      respectively). CONCLUSION: Higher MPV and PDW are associated with increased risk
      of death, whereas the decrease in plateletcrit is associated with increased
      mortality risk.

PMID- 24895094
TI  - Physicochemical properties of newly developed bioactive glass cement and its
      effects on various cells.
AB  - Biomaterials used in dental treatments are expected to have favorable properties
      such as biocompatibility and an ability to induce tissue formation in dental pulp
      and periapical tissue, as well as sealing to block external stimuli. Bioactive
      glasses have been applied in bone engineering, but rarely applied in the field of
      dentistry. In the present study, bioactive glass cement for dental treatment was
      developed, and then its physicochemical properties and effects on cell responses
      were analyzed. To clarify the physicochemical attributes of the cement, field
      emission scanning electron microscopy, X-ray diffraction, and pH measurement were
      carried out. Cell attachment, morphology, and viability to the cement were also
      examined to clarify the effects of the cement on odontoblast-like cells (KN-3
      cells), osteoblastic cells (MC3T3-E1 cells), human periodontal ligament
      stem/progenitor cells and neuro-differentiative cells (PC-12 cells).
      Hydroxyapatite-like precipitation was formed on the surface of the hardened
      cement and the pH level changed from pH10 to pH9, then stabilized in simulate
      body fluid. The cement had no cytotxic effects on these cells, and particulary
      induced process elongation of PC-12 cells. Our results suggest that the newly
      developed bioactive glass cement have capability of the application in dental
      procedures as bioactive cement.

PMID- 24895090
TI  - Measuring short-term liver metabolism non-invasively: postprandial and post
      exercise 1H and 31P MR spectroscopy.
AB  - OBJECT: The objective of this study was to determine the effects of a
      standardized fat rich meal and subsequent exercise on liver fat content by 1H MRS
      and on liver adenosine triphosphate (ATP) content by 31P MRS in healthy subjects.
      MATERIALS AND METHODS: Hepatic 1H and proton decoupled 31P MRS were performed on
      nine healthy subjects on a clinical 3.0 T MR imager three times during a day:
      after (1) an overnight fast, (2) a following standardized fat rich meal and (3) a
      subsequent exercise session. Blood parameters were followed during the day to
      serve as a reference to MRS. RESULTS: Liver fat content increased gradually over
      the day (p = 0.0001) with an overall increase of 30 %. Also gamma-NTP changed
      significantly over the day (p = 0.005). gamma-NTP/tP decreased by 9 % (p = 0.019,
      post hoc) from the postprandial to the post-exercise state. CONCLUSION: Our study
      shows that in vivo MRS can depict short lived physiological changes; entering of
      fat into liver cells and consumption of ATP during exercise can be measured non
      invasively in healthy subjects. The physiological state may have an impact on fat
      and energy metabolite levels. Hepatic 1H and 31P MRS studies should be performed
      under standardized conditions.

PMID- 24895095
TI  - [NiFe]Hydrogenase from Citrobacter sp. S-77 surpasses platinum as an electrode
      for H2 oxidation reaction.
AB  - Reported herein is an electrode for dihydrogen (H2) oxidation, and it is based on
      [NiFe]Hydrogenase from Citrobacter sp. S-77 ([NiFe]S77). It has a 637 times
      higher mass activity than Pt (calculated based on 1 mg of [NiFe]S77 or Pt) at 50
      mV in a hydrogen half-cell. The [NiFe]S77 electrode is also stable in air and,
      unlike Pt, can be recovered 100 % after poisoning by carbon monoxide. Following
      characterization of the [NiFe]S77 electrode, a fuel cell comprising a [NiFe]S77
      anode and Pt cathode was constructed and shown to have a a higher power density
      than that achievable by Pt.

PMID- 24895096
TI  - Visible-light photocatalytic hydrogen production activity of ZnIn2 S4
      microspheres using carbon quantum dots and platinum as dual co-catalysts.
AB  - ZnIn(2)S(4) microspheres (ZIS MSs) were for the first time decorated with carbon
      quantum dots (CQDs) and platinum nanoparticles (NPs) as dual co-catalysts of for
      photocatalytic H(2) production. The ZIS MSs co-loaded with CQDs and Pt exhibited
      a high photocatalytic H2 production rate of 1032.2 MUmol h(-1)  g(-1) with an
      apparent quantum efficiency of 2.2 % (420 nm) in triethanolamine aqueous solution
      under visible-light irradiation, which was much higher than the respective
      photocatalytic rates of pure ZIS, Pt loaded ZIS, and CQDs-decorated ZIS. Such a
      great enhancement was attributed to the integrative effect of good
      crystallization, enhanced light absorption, high electrical conductivity of CQDs,
      and the vectorial electron transfer from ZIS to CQDs and Pt NPs (ZIS->CQDs->Pt).

PMID- 24895098
TI  - The first tandem, all-exciplex-based WOLED.
AB  - Exploiting our recently developed bilayer interface methodology, together with a
      new wide energy-gap, low LUMO acceptor (A) and the designated donor (D) layers,
      we succeeded in fabricating an exciplex-based organic light-emitting diode (OLED)
      systematically tuned from blue to red. Further optimization rendered a record
      high blue exciplex OLED with eta(ext) of 8%. We then constructed a device
      structure configured by two parallel blend layers of mCP/PO-T2T and DTAF/PO-T2T,
      generating blue and yellow exciplex emission, respectively. The resulting device
      demonstrates for the first time a tandem, all-exciplex-based white-light OLED
      (WOLED) with excellent efficiencies eta(ext): 11.6%, eta(c): 27.7 cd A(-1), and
      eta(p): 15.8 ml W(-1) with CIE(0.29, 0.35) and CRI 70.6 that are nearly
      independent of EL intensity. The tandem architecture and blend-layer D/A (1:1)
      configuration are two key elements that fully utilize the exciplex delay
      fluorescence, providing a paragon for the use of low-cost, abundant organic
      compounds en route to commercial WOLEDs.

PMID- 24895097
TI  - Impact of combined lipid lowering with blood pressure control on coronary plaque
      regression: rationale and design of MILLION study.
AB  - A line of epidemiological studies suggests that the accumulation of coronary risk
      factors promotes the progression of coronary atherosclerosis. Recent clinical
      studies showed that aggressive low-density lipoprotein (LDL) cholesterol-lowering
      therapy using statins could regress coronary atheroma and reduce major
      cardiovascular events. Additionally, therapy that controlled amlodipine-based
      blood pressure reduced major cardiovascular events in patients with hypertension
      compared with an atenolol-based regimen. An open-label randomized multicenter
      study is primarily planned to evaluate the changes in coronary atheroma volume
      using intravascular ultrasonography 18-24 months after intensive lowering of LDL
      cholesterol and blood pressure compared with a standard therapy indicated by
      current guidelines in Japanese patients with coronary artery disease (CAD). The
      secondary endpoints include changes in serum lipid levels, inflammatory markers,
      glucose markers and blood pressure. In total, 100 subjects with CAD who are
      undergoing percutaneous coronary intervention will be tested. The MILLION study
      will provide new evidence and therapeutic standards for the prevention of CAD in
      Japanese patients by controlling both LDL-C levels and blood pressure. 

PMID- 24895099
TI  - Sodium glucose co-transporter 2 inhibitors: a novel approach to the management of
      type 2 diabetes mellitus.
AB  - PURPOSE: The purpose of this article is to educate nurse practitioners about the
      newest class of oral medications developed to treat type 2 diabetes mellitus
      (T2DM). This article will review dapagliflozin and canagliflozin, the two Food
      and Drug Administration (FDA) approved sodium glucose co-transporter 2 (SGLT2)
      inhibitors, and discuss their place in therapy. DATA SOURCES: A comprehensive
      literature search was conducted using MEDLINE with the key terms: dapagliflozin,
      canagliflozin, SGLT2 inhibitors, and SGLT2 inhibitors. Other resources included
      the World Health Organization (WHO), U.S. FDA, Centers for Disease Control and
      Prevention (CDC), clinical guidelines, FDA labeling, briefings, and press
      releases. CONCLUSIONS: Dapagliflozin and canagliflozin appear to be safe and
      moderately effective. SGLT2 inhibitors provide an alternative for dual and triple
      therapy for T2DM or can be used as monotherapy in patients who cannot tolerate
      other first-line options. IMPLICATIONS FOR PRACTICE: SGLT2 inhibitors have a
      unique, insulin-independent mechanism of action, targeting the kidneys. They have
      a low incidence of hypoglycemia and result in a moderate reduction in HbA1C.
      Improvements in weight, blood pressure, and lipid parameters have been
      demonstrated. Dosing considerations are required for the elderly, renally
      impaired, and patients at risk for hypotension.

PMID- 24895103
TI  - Lawyer threatens action against GMC after undercover staff attended confidential
      discussions with her client.

PMID- 24895100
TI  - Accumulation of FLT3(+) CD11c (+) dendritic cells in psoriatic lesions and the
      anti-psoriatic effect of a selective FLT3 inhibitor.
AB  - Psoriasis is a common chronic T-cell-mediated autoimmune skin disease, and
      traditional immunotherapies for psoriasis have focused on the direct inhibition
      of T cells, which often causes toxicity and lacks long-term effectiveness. Safe
      and effective therapeutic strategies are strongly needed for psoriasis. In this
      study, we show for the first time a significant accumulation of FLT3(+) CD11c(+)
      dendritic cells (DCs) in human psoriatic lesions and in the skin of experimental
      preclinical K14-VEGF transgenic homozygous mice, our animal model, although not
      an exact match for human psoriasis, displays many characteristics of inflammatory
      skin inflammation. SKLB4771, a potent and selective FLT3 inhibitor that we
      designed and synthesised, was used to treat cutaneous inflammation and psoriasis
      like symptoms of disease in mice and almost completely cured the psoriasis-like
      disease without obvious toxicity. Mechanistic studies indicated that SKLB4771
      treatment significantly decreased the number and activation of pDCs and mDCs in
      vitro and in vivo, and subsequent T-cell cascade reactions mediated by Th1/Th17
      pathways. These findings show that targeted inhibition of FLT3, and hence direct
      interference with DCs, may be a novel therapeutic approach for the treatment of
      psoriasis. 

PMID- 24895105
TI  - Fewer themes, more stories: shall we consider alternative ways for representing
      complexity well?

PMID- 24895104
TI  - The effect of gender medicine education in GP training: a prospective cohort
      study.
AB  - The purpose of this study is to compare the change in general practitioner (GP)
      trainees' gender awareness following a modular gender medicine programme or a
      mainstream gender medicine programme. In 2007, a prospective study was conducted
      in three cohorts of in total 207 GP trainees who entered GP training in the
      Netherlands. The outcome measure was the Nijmegen Gender Awareness in Medicine
      Scale and a 16-item gender knowledge questionnaire. Two gender medicine teaching
      methods were compared: a modular approach (n = 75) versus a mainstream approach
      (n = 72). Both strategies were compared with a control cohort (n = 60).
      Statistical analysis included analysis of variance and t-tests. The overall
      response rates for the modular, mainstream and control cohort were 78, 72 and 82
      %, respectively. There was a significant difference in change in gender knowledge
      scores between the modular cohort compared with the mainstream and control cohort
      (p = 0.049). There were no statistical differences between the cohorts on gender
      sensitivity and gender role ideology. At entry and end, female GP trainees
      demonstrated significantly higher gender awareness than male GP trainees. A
      modular teaching method is not a more favourable educational method to teach
      gender medicine in GP training. Female GP trainees are more gender aware, but
      male GP trainees are not unaware of gender-related issues. 

PMID- 24895101
TI  - Purified monomeric ligand.MD-2 complexes reveal molecular and structural
      requirements for activation and antagonism of TLR4 by Gram-negative bacterial
      endotoxins.
AB  - A major focus of work in our laboratory concerns the molecular mechanisms and
      structural bases of Gram-negative bacterial endotoxin recognition by host (e.g.,
      human) endotoxin-recognition proteins that mediate and/or regulate activation of
      Toll-like receptor (TLR) 4. Here, we review studies of wild-type and variant
      monomeric endotoxin.MD-2 complexes first produced and characterized in our
      laboratories. These purified complexes have provided unique experimental
      reagents, revealing both quantitative and qualitative determinants of TLR4
      activation and antagonism. This review is dedicated to the memory of Dr. Theresa
      L. Gioannini (1949-2014) who played a central role in many of the studies and
      discoveries that are reviewed. 

PMID- 24895106
TI  - Conscious versus unconscious thinking in the medical domain: the deliberation
      without-attention effect examined.
AB  - Previous studies have shown that with important decisions, unconscious thought
      has surprisingly led to better choices than conscious thought. The present study
      challenges this so-called 'deliberation-without-attention effect' in the medical
      domain. In a computerized study, physicians and medical students were asked,
      after either conscious or unconscious thought, to estimate the 5-year survival
      probabilities of four fictitious patients with varying medical characteristics.
      We assumed that experienced physicians would outperform students as a result of
      their superior knowledge. The central question was whether unconscious thought in
      this task would lead to better performance in experts or novices, in line with
      the deliberation-without-attention effect. We created four fictitious male 60
      year-old patients, each of whom with signs and symptoms related to likely
      prognosis, from 12 (Complex) or 4 (Simple) categories. This manipulation resulted
      in objectively different life expectancies for these patients. Participants (86
      experienced physicians and 57 medical students) were randomly allocated to the
      Simple or Complex condition. Statements were randomly presented for 8 s. Next,
      each participant assessed the life expectancies after either conscious or
      unconscious thought. As expected, experienced physicians were better in assessing
      life expectancies than medical students. No significant differences were found in
      performance between conscious and unconscious thought, nor did we detect a
      significant interaction between expertise level and mode of thought. In a medical
      decision task, unconscious thought did not lead to better performance of
      experienced physicians or medical students than conscious thought. Our findings
      do not support the deliberation-without-attention effect. 

PMID- 24895107
TI  - Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome
      patients.
AB  - Adipose tissue (AT) is a key organ in the regulation of total body lipid
      homeostasis, which is responsible for the storage and release of fatty acids
      according to metabolic needs. We aimed to investigate the effect of the quantity
      and quality of dietary fat on the lipogenesis and lipolysis processes in the AT
      of metabolic syndrome (MetS) patients. A randomized, controlled trial conducted
      within the LIPGENE study assigned MetS patients to one of four diets: (a) high
      saturated fatty acid (HSFA) (b) high-monounsaturated fatty acid, and (c, d) two
      low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3
      (LFHCC n-3) polyunsaturated fatty acids (PUFA) or placebo (LFHCC), for 12 weeks
      each. A fat challenge reflecting the same fatty acid composition as the original
      diets was conducted post-intervention. Long-term consumption of the LFHCC diet
      induced an increase in the fasting expression levels of the sterol regulatory
      element binding protein-1 and stearoyl-CoA desaturase D9-desaturase genes,
      whereas the supplementation of this diet with n-3 PUFA reversed this effect (p =
      0.007). In contrast, long-term consumption of the HSFA diet increased the
      expression of the adipose triglyceride lipase (ATGL) gene, at both fasting and
      postprandial states (both, p < 0.001). Our results showed the anti-lipogenic
      effect exerted by LC n-3 PUFA when administered together with a LFHCC diet.
      Conversely, a diet high in saturated fat increased the expression of the
      lipolytic gene ATGL relative to the other diets. 

PMID- 24895108
TI  - Dose response of umeclidinium administered once or twice daily in patients with
      COPD: a pooled analysis of two randomized, double-blind, placebo-controlled
      studies.
AB  - Umeclidinium (UMEC) is an inhaled long-acting muscarinic antagonist approved in
      the US and EU for the once-daily (QD) treatment of chronic obstructive pulmonary
      disease (COPD); it is not indicated for the treatment of asthma. To fully
      characterize the dose-response relationship of UMEC in patients with COPD, a
      pooled analysis of data from two randomized, placebo-controlled, cross-over, dose
      ranging studies was performed, evaluating UMEC at doses of 15.6-1000 mcg QD and
      15.6-250 mcg twice daily (BID). The primary endpoint was trough forced expiratory
      volume in one second (FEV(1)) at the end of each study's treatment period (Day
      8/Day 15). A population model-based analysis using total daily UMEC dose was used
      for the primary analysis comparing QD and BID dosing. A physiological effect
      (E(max)) model was optimal in defining the relationship between UMEC dose and the
      primary endpoint, demonstrating a clear monotonic dose response over QD and BID
      dosing regimens. UMEC doses >=62.5 mcg QD were differentiated from lower doses
      and BID dosing did not provide benefit over QD dosing. The potency (ED(50))
      estimate was 33 mcg with QD dosing. These data indicate that UMEC 62.5 mcg and
      125 mcg QD provide lung function benefits that warrant further investigation for
      the treatment of COPD.

PMID- 24895109
TI  - Continuous-flow microfluidic blood cell sorting for unprocessed whole blood using
      surface-micromachined microfiltration membranes.
AB  - White blood cells (WBCs) constitute about 0.1% of the blood cells, yet they play
      a critical role in innate and adaptive immune responses against pathogenic
      infections, allergic conditions, and malignancies and thus contain rich
      information about the immune status of the body. Rapid isolation of WBCs directly
      from whole blood is a prerequisite for any integrated immunoassay platform
      designed for examining WBC phenotypes and functions; however, such functionality
      is still challenging for blood-on-a-chip systems, as existing microfluidic cell
      sorting techniques are inadequate for efficiently processing unprocessed whole
      blood on chip with concurrent high throughput and cell purity. Herein we report a
      microfluidic chip for continuous-flow isolation and sorting of WBCs from whole
      blood with high throughput and separation efficiency. The microfluidic cell
      sorting chip leveraged the crossflow filtration scheme in conjunction with a
      surface-micromachined poly(dimethylsiloxane) (PDMS) microfiltration membrane
      (PMM) with high porosity. With a sample throughput of 1 mL h(-1), the
      microfluidic cell sorting chip could recover 27.4 +/- 4.9% WBCs with a purity of
      93.5 +/- 0.5%. By virtue of its separation efficiency, ease of sample recovery,
      and high throughput enabled by its continuous-flow operation, the microfluidic
      cell sorting chip holds promise as an upstream component for blood sample
      preparation and analysis in integrated blood-on-a-chip systems. 

PMID- 24895111
TI  - What explains the quality and price of GP services? An investigation using linked
      survey and administrative data.
AB  - We examine patient socioeconomic status, the strength of the patient-doctor
      relationship and local area competition as determinants of the quality and price
      of GP services. We exploit a large-sample patient data set in Australia and its
      linkage to administrative databases. The sample contains over 260,000 patients
      and over 12,600 GPs, observed between 2005 and 2010. Controlling for GP fixed
      effects and patient health, we find no strong evidence that quality differs by
      patient age, gender, country of origin, health concession card status and income,
      but quality is increased by stronger patient-doctor relationship. Using a
      competition measure that is defined at the individual GP level and not restricted
      to a local market, we find that competition lowers quality. Price is increasing
      in patient income, whereas competition has a small impact on price.

PMID- 24895110
TI  - Host STAT2/type I interferon axis controls tumor growth.
AB  - The role of STAT2 in mediating the antigrowth effects of type I interferon (IFN)
      is well-documented in vitro. Yet evidence of IFN-activated STAT2 as having tumor
      suppressor function in vivo and participation in antitumor immunity is lacking.
      Here we show in a syngeneic tumor transplantation model that STAT2 reduces tumor
      growth. Stat2(-/-) mice formed larger tumors compared to wild type (WT) mice. IFN
      beta treatment of Stat2(-/-) mice did not cause tumor regression. Gene expression
      analysis revealed a small subset of immunomodulatory genes to be downregulated in
      tumors established in Stat2(-/-) mice. Additionally, we found tumor antigen cross
      presentation by Stat2(-/-) dendritic cells to T cells to be impaired. Adoptive
      transfer of tumor antigen specific CD8(+) T cells primed by Stat2(-/-) dendritic
      cells into tumor-bearing Stat2(-/-) mice did not induce tumor regression with IFN
      beta intervention. We observed that an increase in the number of CD4(+) and
      CD8(+) T cells in the draining lymph nodes of IFN-beta-treated tumor-bearing WT
      mice was absent in IFN-beta treated Stat2(-/-) mice. Thus our study provides
      evidence for further evaluation of STAT2 function in cancer patients receiving
      type I IFN based immunotherapy.

PMID- 24895112
TI  - Soil phosphorus constrains biodiversity across European grasslands.
AB  - Nutrient pollution presents a serious threat to biodiversity conservation. In
      terrestrial ecosystems, the deleterious effects of nitrogen pollution are
      increasingly understood and several mitigating environmental policies have been
      developed. Compared to nitrogen, the effects of increased phosphorus have
      received far less attention, although some studies have indicated that phosphorus
      pollution may be detrimental for biodiversity as well. On the basis of a dataset
      covering 501 grassland plots throughout Europe, we demonstrate that, independent
      of the level of atmospheric nitrogen deposition and soil acidity, plant species
      richness was consistently negatively related to soil phosphorus. We also
      identified thresholds in soil phosphorus above which biodiversity appears to
      remain at a constant low level. Our results indicate that nutrient management
      policies biased toward reducing nitrogen pollution will fail to preserve
      biodiversity. As soil phosphorus is known to be extremely persistent and we found
      no evidence for a critical threshold below which no environmental harm is
      expected, we suggest that agro-environmental schemes should include grasslands
      that are permanently free from phosphorus fertilization. 

PMID- 24895113
TI  - Choosing a cancer surgeon: analyzing factors in patient decision making using a
      best-worst scaling methodology.
AB  - BACKGROUND: Surgeon experience has been shown to influence outcomes for many
      types of cancer. The factors that patients consider when selecting a hospital or
      surgeon for cancer treatment remain poorly defined. METHODS: All patients with a
      cancer diagnosis seeking treatment at a surgical clinic at Johns Hopkins Hospital
      were asked to participate. A survey utilizing a best-worst scaling methodology
      was constructed to elicit the importance of various factors when selecting a
      cancer surgeon. Attributes were grouped into four categories: surgeon reputation,
      surgeon qualifications, hospital-related factors, and nonclinical factors.
      RESULTS: Two hundred fourteen patients with a cancer diagnosis participated in
      the study (82.0 % response rate). Patients placed the highest value on physician
      qualifications and hospital-related factors. Specifically, surgeon case-specific
      experience (coefficient 2.56, SE 0.06) and the receipt of specialized training by
      the surgeon (coefficient 2.32, SE 0.06) ranked highest (both P < 0.001). Among
      hospital-related factors, hospital case-specific volume (coefficient 1.32, SE
      0.06; P < 0.001) was most important. The lowest rated factors were parking
      availability (coefficient -2.81, SE 0.06) and home-to-clinic distance
      (coefficient -2.12, SE 0.06) (both P < 0.001). The majority of patients reported
      their ideal surgeon to have at least 6 years of experience (n = 143, 68.1 %) and
      to have performed their specific procedure at least 50 times (n = 156, 75.3 %).
      CONCLUSIONS: Patients consider several factors when choosing a cancer surgeon.
      Surgeon qualifications and hospital-related factors appear to be most influential
      in their decision. Easier and more widespread dissemination of surgeon and
      hospital cancer data such as case volume may be useful for patients.

PMID- 24895115
TI  - Organocatalytic enantio- and diastereoselective conjugate addition to
      nitroolefins: when beta-ketoamides surpass beta-ketoesters.
AB  - Our findings on the bifunctional squaramide-catalyzed enantioselective conjugate
      addition of beta-ketoamides to nitroolefins are disclosed. It appears that simple
      acyclic methylene beta-ketoamides, unlike the extensively studied beta
      ketoesters, afford the products in excellent diastereoselectivities, and maintain
      high yields and enantioselectivities. Moreover, competition and kinetic studies
      were conducted to rationalize the observed reactivity and selectivity. The high
      level of diastereocontrol, along with the amenability of the amide group to
      postfunctionalization, dramatically increase the synthetic usefulness of the
      transformation. 

PMID- 24895114
TI  - Concomitant seminal vesicle invasion in pT4a urothelial carcinoma of the bladder
      with contiguous prostatic infiltration is an adverse prognosticator for cancer
      specific survival after radical cystectomy.
AB  - PURPOSE: To evaluate the prognostic value of concomitant seminal vesicle invasion
      (cSVI) in patients with urothelial carcinoma of the bladder (UCB) and contiguous
      prostatic stromal infiltration in a large cystectomy series. METHODS: A total of
      385 patients with UCB and contiguous prostatic infiltration comprised our study.
      Patients were divided in two groups according to cSVI. Median follow-up was 36
      months (interquartile range 11-74); the primary end point was cancer-specific
      mortality. The prognostic impact of cSVI was evaluated using multivariable Cox
      regression analysis. The predictive accuracy was assessed by a receiver operating
      characteristic analysis. RESULTS: A total of 229 patients (59.5 %) without cSVI
      comprised group A, and 156 patients (40.5 %) with cSVI comprised group B.
      Positive lymph nodes (63 vs. 44 %, p < 0.001) and positive surgical margins (34 %
      vs. 14 %, p < 0.001) were more common in patients with cSVI. The 5- and 10-year
      cancer-specific survival rates were 41 % and 32 % (group A) and 21 and 17 %
      (group B) (p < 0.001). In multivariable analysis, pathological nodal stage
      (hazard ratio [HR] 2.19, p < 0.001), soft tissue surgical margin (HR 1.57, p =
      0.010), clinical tumor stage (HR 1.46, p = 0.010), adjuvant chemotherapy (HR
      0.40, p < 0.001), and cSVI (HR 1.69, p < 0.001) independently impacted cancer
      specific mortality. The c-indices of the multivariable models with and without
      inclusion of cSVI were 0.658 (95 % confidence interval 0.60-0.71) and 0.635 (95 %
      confidence interval 0.58-0.69), respectively, resulting in a predictive accuracy
      gain of 2.3 % (p = 0.002). CONCLUSIONS: In patients with UCB and prostatic
      stromal invasion, cSVI adversely affected cancer-specific survival compared to
      patients without cSVI. The inclusion of cSVI significantly improved the
      predictive accuracy of our multivariable model regarding survival.

PMID- 24895117
TI  - Phase transition originating from order-disorder transformations of carboxy
      oxygen atoms coupled with dynamic proton motions in [PhCH2 NH(CH3)2]2 C2O4?H2
      C2O4.
AB  - A new molecular phase transition material, [PhCH(2) NH(CH(3))(2)](2)
      C(2)O(4)?H(2)C(2)O(4), which undergoes a reversible phase transition at 151.6 K,
      has been successfully synthesized. Differential scanning calorimetry (DSC),
      specific heat capacity, and dielectric measurements confirm its reversible phase
      transition with a large thermal hysteresis of 15.1 K, demonstrating that the
      phase transition is typical first order. Variable-temperature single-crystal X
      ray diffraction analyses reveal that the order-disorder transformations of
      carboxy oxygen atoms induce the structural phase transition. A slight
      reorientation of the oxalic acid unit is discovered to accompany the ordering of
      carboxy oxygen atoms at low temperature. The DSC measurement result of the
      deuterated analog is different to that of 1, indicating that proton dynamic
      motions in hydrogen bonds also contribute to the phase transition.

PMID- 24895118
TI  - Identification of a novel inhibition site in translocase MraY based upon the site
      of interaction with lysis protein E from bacteriophage phiX174.
AB  - Translocase MraY is the site of action of lysis protein E from bacteriophage
      phiX174. Previous genetic studies have shown that mutation F288L in transmembrane
      helix 9 of E. coli MraY confers resistance to protein E. Construction of a
      helical wheel model for transmembrane helix 9 of MraY and the transmembrane
      domain of protein E enabled the identification of an Arg-Trp-x-x-Trp (RWxxW)
      motif in protein E that might interact with Phe288 of MraY and the neighbouring
      Glu287. This motif is also found in a number of cationic antimicrobial peptide
      sequences. Synthetic dipeptides and pentapeptides based on the RWxxW consensus
      sequence showed inhibition of particulate E. coli MraY activity (IC50 200-600
      MUM), and demonstrated antimicrobial activity against E. coli (MIC 31-125 MUg mL(
      1)). Cationic antimicrobial peptides at a concentration of 100 MUg mL(-1)
      containing Arg-Trp sequences also showed 30-60 % inhibition of E. coli MraY
      activity. Assay of the synthetic peptide inhibitors against recombinant MraY
      enzymes from Bacillus subtilis, Pseudomonas aeruginosa, and Micrococcus flavus
      (all of which lack Phe288) showed reduced levels of enzyme inhibition, and assay
      against recombinant E. coli MraY F288L and an E287A mutant demonstrated either
      reduced or no detectable enzyme inhibition, thus indicating that these peptides
      interact at this site. The MIC of Arg-Trp-octyl ester against E. coli was
      increased eightfold by overexpression of mraY, and was further increased by
      overexpression of the mraY mutant F288L, also consistent with inhibition at the
      RWxxW site. As this site is on the exterior face of the cytoplasmic membrane, it
      constitutes a potential new site for antimicrobial action, and provides a new
      cellular target for cationic antimicrobial peptides.

PMID- 24895116
TI  - The effect of terminal sterilization on structural and biophysical properties of
      a decellularized collagen-based scaffold; implications for stem cell adhesion.
AB  - Terminal sterilization induces physical and chemical changes in the extracellular
      matrix (ECM) of ex vivo-derived biomaterials due to their aggressive mechanism of
      action. Prior studies have focused on how sterilization affects the mechanical
      integrity of tissue-based biomaterials but have rarely characterized effects on
      early cellular interaction, which is indicative of the biological response. Using
      a model fibrocartilage disc scaffold, these investigations compare the effect of
      three common sterilization methods [peracetic acid (PAA), gamma irradiation (GI),
      and ethylene oxide (EtO)] on a range of material properties and characterized
      early cellular interactions. GI and EtO produced unfavorable structural damage
      that contributed to inferior cell adhesion. Conversely, exposure to PAA resulted
      in limited structural alterations while inducing chemical modifications that
      favored cell attachment. Results suggest that the sterilization approach can be
      selected to modulate biomaterial properties to favor cellular adhesion and has
      relevance in tissue engineering and regenerative medicine applications.
      Furthermore, the study of cellular interactions with modified biomaterials in
      vitro provides information of how materials may react in subsequent clinical
      applications.

PMID- 24895119
TI  - A colorimetric and ratiometric fluorescent probe for distinguishing cysteine from
      biothiols in water and living cells.
AB  - A merocyanine-based highly selective colorimetric and ratiometric fluorescent
      probe is described for Cys detection in water and diluted deproteinized human
      serum. Upon reaction with Cys in aqueous buffer solution, the probe showed a
      dramatic color change from faint yellow to pink and remarkable ratiometric
      fluorescence enhancement signals were also observed, which are ascribed to an
      intramolecular charge transfer (ICT) process. This strategy was based on
      modulating the merocyanine pi-electron system by conjugation and removal of the
      acrylate group to release the chromophore group, resulting in a specific
      colorimetry and fluorescence response. The probe has low cytotoxicity and good
      cell permeability. It is readily employed for assessing the change of the
      intracellular Cys level. 

PMID- 24895120
TI  - DNA methyltransferase 3a and mitogen-activated protein kinase signaling regulate
      the expression of fibroblast growth factor-inducible 14 (Fn14) during denervation
      induced skeletal muscle atrophy.
AB  - The TWEAK-fibroblast growth factor-inducible 14 (Fn14) system is a critical
      regulator of denervation-induced skeletal muscle atrophy. Although the expression
      of Fn14 is a rate-limiting step in muscle atrophy on denervation, mechanisms
      regulating gene expression of Fn14 remain unknown. Methylation of CpG sites
      within promoter region is an important epigenetic mechanism for gene silencing.
      Our study demonstrates that Fn14 promoter contains a CpG island close to
      transcription start site. Fn14 promoter also contains multiple consensus DNA
      sequence for transcription factors activator protein 1 (AP1) and specificity
      protein 1 (SP1). Denervation diminishes overall genomic DNA methylation and
      causes hypomethylation at specific CpG sites in Fn14 promoter leading to the
      increased gene expression of Fn14 in skeletal muscle. Abundance of DNA
      methyltransferase 3a (Dnmt3a) and its interaction with Fn14 promoter are
      repressed in denervated skeletal muscle of mice. Overexpression of Dnmt3a
      inhibits the gene expression of Fn14 and attenuates skeletal muscle atrophy upon
      denervation. Denervation also causes the activation of ERK1/2, JNK1/2, and ERK5
      MAPKs and AP1 and SP1, which stimulate the expression of Fn14 in skeletal muscle.
      Collectively, our study provides novel evidence that Dnmt3a and MAPK signaling
      regulate the levels of Fn14 in skeletal muscle on denervation. 

PMID- 24895121
TI  - Siglec-E promotes beta2-integrin-dependent NADPH oxidase activation to suppress
      neutrophil recruitment to the lung.
AB  - Siglec-E is a sialic acid-binding Ig-like lectin expressed on murine myeloid
      cells. It has recently been shown to function as a negative regulator of beta2
      integrin-dependent neutrophil recruitment to the lung following exposure to
      lipopolysaccharide (LPS). Here, we demonstrate that siglec-E promoted neutrophil
      production of reactive oxygen species (ROS) following CD11b beta2-integrin
      ligation with fibrinogen in a sialic acid-dependent manner, but it had no effect
      on ROS triggered by a variety of other stimulants. Siglec-E promotion of ROS was
      likely mediated via Akt activation, because siglec-E-deficient neutrophils plated
      on fibrinogen exhibited reduced phosphorylation of Akt, and the Akt inhibitor,
      MK2206, blocked fibrinogen-induced ROS. In vivo imaging showed that siglec-E also
      promoted ROS in acutely inflamed lungs following exposure of mice to LPS.
      Importantly, siglec-E-promoted ROS were required for its inhibitory function, as
      the NADPH oxidase inhibitor, apocynin, reversed the siglec-E-mediated suppression
      of neutrophil recruitment and blocked neutrophil ROS production in vitro. Taken
      together, these results demonstrate that siglec-E functions as an inhibitory
      receptor of neutrophils via positive regulation of NADPH oxidase activation and
      ROS production. Our findings have implications for the inhibitory role of siglec
      9 on human neutrophils in sepsis and acute lung injury. 

PMID- 24895122
TI  - Aspergillus oryzae CsyB catalyzes the condensation of two beta-ketoacyl-CoAs to
      form 3-acetyl-4-hydroxy-6-alkyl-alpha-pyrone.
AB  - The type III polyketide synthases from fungi produce a variety of secondary
      metabolites including pyrones, resorcinols, and resorcylic acids. We previously
      reported that CsyB from Aspergillus oryzae forms alpha-pyrone csypyrone B
      compounds when expressed in A. oryzae. Feeding experiments of labeled acetates
      indicated that a fatty acyl starter is involved in the reaction catalyzed by
      CsyB. Here we report the in vivo and in vitro reconstitution analysis of CsyB.
      When CsyB was expressed in Escherichia coli, we observed the production of 3
      acetyl-4-hydroxy-alpha-pyrones with saturated or unsaturated straight aliphatic
      chains of C9-C17 in length at the 6 position. Subsequent in vitro analysis using
      recombinant CsyB revealed that CsyB could accept butyryl-CoA as a starter
      substrate and malonyl-CoA and acetoacetyl-CoA as extender substrates to form 3
      acetyl-4-hydroxy-6-propyl-alpha-pyrone. CsyB also afforded dehydroacetic acid
      from two molecules of acetoacetyl-CoA. Furthermore, synthetic N-acetylcysteamine
      thioester of beta-ketohexanoic acid was converted to 3-butanoyl-4-hydroxy-6
      propyl-alpha-pyrone by CsyB. These results therefore confirmed that CsyB
      catalyzed the synthesis of beta-ketoacyl-CoA from the reaction of the starter
      fatty acyl CoA thioesters with malonyl-CoA as the extender through
      decarboxylative condensation and further coupling with acetoacetyl-CoA to form 3
      acetyl-4-hydroxy-6-alkyl-alpha-pyrone. CsyB is the first type III polyketide
      synthase that synthesizes 3-acetyl-4-hydroxy-6-alkyl-alpha-pyrone by catalyzed
      the coupling of two beta-ketoacyl-CoAs. 

PMID- 24895123
TI  - An oncogenic protein Golgi phosphoprotein 3 up-regulates cell migration via
      sialylation.
AB  - Recently, the Golgi phosphoprotein 3 (GOLPH3) and its yeast homolog Vps74p have
      been characterized as essential for the Golgi localization of glycosyltransferase
      in yeast. GOLPH3 has been identified as a new oncogene that is commonly amplified
      in human cancers to modulate mammalian target of rapamycin signaling. However,
      the molecular mechanisms of the carcinogenic signaling pathway remain largely
      unclear. To investigate whether the expression of GOLPH3 was involved in the
      glycosylation processes in mammalian cells, and whether it affected cell
      behavior, we performed a loss-of-function study. Cell migration was suppressed in
      GOLPH3 knockdown (KD) cells, and the suppression was restored by a re
      introduction of the GOLPH3 gene. HPLC and LC/MS analysis showed that the
      sialylation of N-glycans was specifically decreased in KD cells. The specific
      interaction between sialyltransferases and GOLPH3 was important for the
      sialylation. Furthermore, overexpression of alpha2,6-sialyltransferase-I rescued
      cell migration and cellular signaling, both of which were blocked in GOLPH3
      knockdown cells. These results are the first direct demonstration of the role of
      GOLPH3 in N-glycosylation to regulate cell biological functions.

PMID- 24895124
TI  - Activation of epidermal growth factor receptor mediates mucin production
      stimulated by p40, a Lactobacillus rhamnosus GG-derived protein.
AB  - The mucus layer coating the gastrointestinal tract serves as the first line of
      intestinal defense against infection and injury. Probiotics promote mucin
      production by goblet cells in the intestine. p40, a Lactobacillus rhamnosus GG
      derived soluble protein, has been shown to transactivate the EGF receptor (EGFR)
      in intestinal epithelial cells, which is required for inhibition of apoptosis and
      preservation of barrier function in the colon, thereby ameliorating intestinal
      injury and colitis. Because activation of EGFR has been shown to up-regulate
      mucin production in goblet cells, the purpose of this study was to investigate
      the effects and mechanisms of p40 regulation of mucin production. p40 activated
      EGFR and its downstream target, Akt, in a concentration-dependent manner in
      LS174T cells. p40 stimulated Muc2 gene expression and mucin production in LS174T
      cells, which were abolished by inhibition of EGFR kinase activity, down
      regulation of EGFR expression by EGFR siRNA transfection, or suppression of Akt
      activation. Treatment with p40 increased mucin production in the colonic
      epithelium, thus thickening the mucus layer in the colon of wild type, but not of
      Egfr(wa5) mice, which have a dominant negative mutation in the EGFR kinase
      domain. Furthermore, inhibition of mucin-type O-linked glycosylation suppressed
      the effect of p40 on increasing mucin production and protecting intestinal
      epithelial cells from TNF-induced apoptosis in colon organ culture. Thus, these
      results suggest that p40-stimulated activation of EGFR mediates up-regulation of
      mucin production, which may contribute to the mechanisms by which p40 protects
      the intestinal epithelium from injury. 

PMID- 24895125
TI  - Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and
      results in glucocorticoid resistance in a B-lymphoblastic leukemia model.
AB  - Although great advances have been made in the treatment of pediatric acute
      lymphoblastic leukemia, up to one of five patients will relapse, and their
      prognosis thereafter is dismal. We have previously identified recurrent deletions
      in TBL1XR1, which encodes for an F-box like protein responsible for regulating
      the nuclear hormone repressor complex stability. Here we model TBL1XR1 deletions
      in B-precursor ALL cell lines and show that TBL1XR1 knockdown results in reduced
      glucocorticoid receptor recruitment to glucocorticoid responsive genes and
      ultimately decreased glucocorticoid signaling caused by increased levels of
      nuclear hormone repressor 1 and HDAC3. Reduction in glucocorticoid signaling in
      TBL1XR1-depleted lines resulted in resistance to glucocorticoid agonists, but not
      to other chemotherapeutic agents. Importantly, we show that treatment with the
      HDAC inhibitor SAHA restores sensitivity to prednisolone in TBL1XR1-depleted
      cells. Altogether, our data indicate that loss of TBL1XR1 is a novel driver of
      glucocorticoid resistance in ALL and that epigenetic therapy may have future
      application in restoring drug sensitivity at relapse.

PMID- 24895126
TI  - Benzothiophene carboxylate derivatives as novel allosteric inhibitors of branched
      chain alpha-ketoacid dehydrogenase kinase.
AB  - The mitochondrial branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is
      negatively regulated by reversible phosphorylation.BCKDC kinase (BDK) inhibitors
      that augment BCKDC flux have been shown to reduce branched-chain amino acid
      (BCAA) concentrations in vivo. In the present study, we employed high-throughput
      screens to identify compound 3,6- dichlorobenzo[b]thiophene-2-carboxylic acid
      (BT2) as a novel BDK inhibitor (IC(50) = 3.19 MUM). BT2 binds to the same site in
      BDK as other known allosteric BDK inhibitors, including (S)-alpha
      cholorophenylproprionate ((S)-CPP). BT2 binding to BDK triggers helix movements
      in the N-terminal domain, resulting in the dissociation of BDK from the BCKDC
      accompanied by accelerated degradation of the released kinase in vivo. BT2 shows
      excellent pharmacokinetics (terminal T(1/2) = 730 min) and metabolic stability
      (no degradation in 240 min), which are significantly better than those of (S)
      CPP. BT2, its analog 3-chloro-6-fluorobenzo[ b]thiophene-2-carboxylic acid
      (BT2F), and a prodrug of BT2 (i.e. N-(4-acetamido-1,2,5-oxadiazol-3-yl)-3,6
      dichlorobenzo[ b]thiophene-2-carboxamide (BT3)) significantly increase residual
      BCKDC activity in cultured cells and primary hepatocytes from patients and a
      mouse model of maple syrup urine disease. Administration of BT2 at 20 mg/kg/day
      to wild-type mice for 1 week leads to nearly complete dephosphorylation and
      maximal activation of BCKDC in heart, muscle, kidneys, and liver with reduction
      in plasma BCAA concentrations. The availability of benzothiophene carboxylate
      derivatives as stable BDK inhibitors may prove useful for the treatment of
      metabolic disease caused by elevated BCAA concentrations.

PMID- 24895127
TI  - Phosphorylation of eukaryotic translation initiation factor 4E and eukaryotic
      translation initiation factor 4E-binding protein (4EBP) and their upstream
      signaling components undergo diurnal oscillation in the mouse hippocampus:
      implications for memory persistence.
AB  - Translation of mRNA plays a critical role in consolidation of long-term memory.
      Here, we report that markers of initiation of mRNA translation are activated
      during training for contextual memory and that they undergo diurnal oscillation
      in the mouse hippocampus with maximal activity observed during the daytime
      (zeitgeber time 4-8 h). Phosphorylation and activation of eukaryotic translation
      initiation factor 4E (eIF4E), eIF4E-binding protein 1 (4EBP1), ribosomal protein
      S6, and eIF4F cap-complex formation, all of which are markers for translation
      initiation, were higher in the hippocampus during the daytime compared with
      night. The circadian oscillation in markers of mRNA translation was lost in
      memory-deficient transgenic mice lacking calmodulin-stimulated adenylyl cyclases.
      Moreover, disruption of the circadian rhythm blocked diurnal oscillations in
      eIF4E, 4EBP1, rpS6, Akt, and ERK1/2 phosphorylation and impaired memory
      consolidation. Furthermore, repeated inhibition of translation in the hippocampus
      48 h after contextual training with the protein synthesis inhibitor anisomycin
      impaired memory persistence. We conclude that repeated activation of markers of
      translation initiation in hippocampus during the circadian cycle might be
      critical for memory persistence. 

PMID- 24895128
TI  - Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs
      insulin signaling through SIRT1 inactivation.
AB  - To address whether mitochondrial biogenesis is essential for skeletal myogenesis,
      C2C12 myogenesis was investigated after knockdown of NADH dehydrogenase
      (ubiquintone) flavoprotein 1 (NDUFV1), which is an oxidative phosphorylation
      complex I subunit that is the first subunit to accept electrons from NADH. The
      NDUFVI knockdown enhanced C2C12 myogenesis by decreasing the NAD(+)/NADH ratio
      and subsequently inactivating SIRT1 and SIRT1 activators (pyruvate, SRT1720, and
      resveratrol) abolished the NDUFV1 knockdown-induced myogenesis enhancement.
      However, the insulin-elicited activation of insulin receptor beta (IRbeta) and
      insulin receptor substrate-1 (IRS-1) was reduced with elevated levels of protein
      tyrosine phosphatase 1B after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1
      knockdown-induced blockage of insulin signaling was released by protein-tyrosine
      phosphatase 1B knockdown in C2C12 myotubes, and we found that NDUFV1 or SIRT1
      knockdown did not affect mitochondria biogenesis during C2C12 myogenesis. Based
      on these data, we can conclude that complex I dysfunction-induced SIRT1
      inactivation leads to myogenesis enhancement but blocks insulin signaling without
      affecting mitochondria biogenesis. 

PMID- 24895129
TI  - The role of Mg(II) in DNA cleavage site recognition in group II intron ribozymes:
      solution structure and metal ion binding sites of the RNA-DNA complex.
AB  - Group II intron ribozymes catalyze the cleavage of (and their reinsertion into)
      DNA and RNA targets using a Mg2(+)-dependent reaction. The target is cleaved 3'
      to the last nucleotide of intron binding site 1 (IBS1), one of three regions that
      form base pairs with the intron's exon binding sites (EBS1 to -3).We solved the
      NMR solution structure of the d3' hairpin of the Sc.ai5gamma intron containing
      EBS1 in its 11-nucleotide loop in complex with the dIBS1 DNA 7-mer and compare it
      with the analogous RNA-RNA contact. The EBS1-dIBS1 helix is slightly flexible and
      non-symmetric. NMR data reveal two major groove binding sites for divalent metal
      ions at the EBS1-dIBS1 helix, and surface plasmon resonance experiments show that
      low concentrations of Mg2(+) considerably enhance the affinity of dIBS1 for EBS1.
      Our results indicate that identification of both RNA and DNA IBS1 targets,
      presentation of the scissile bond, and stabilization of the structure by metal
      ions are governed by the overall structure of EBS1-dIBS1 and the surrounding loop
      nucleotides but are irrespective of different EBS1-(d)IBS1 geometries and
      interstrand affinities.

PMID- 24895131
TI  - A novel suppressive effect of alcohol dehydrogenase 5 in neuronal
      differentiation.
AB  - Alcohol dehydrogenase 5 (ADH5) is a conserved enzyme for alcohol and aldehyde
      metabolism in mammals. Despite dynamic expression throughout neurogenesis, its
      role in neuronal development remains unknown. Here we present the first evidence
      that ADH5 is a negative regulator of neuronal differentiation. Gene expression
      analyses identify a constant reduction of ADH5 levels throughout neuronal
      development. Overexpression of ADH5 reduces both development and adult neuronal
      differentiation of mouse neurons. This effect depends on the catalytic activity
      of ADH5 and involves ADH5-mediated denitrosation of histone deacetylase 2
      (HDAC2). Our results indicate that ADH5 counteracts neuronal differentiation of
      human neural stem cells and that this effect can be reversed by pharmacological
      inhibition of ADH5. Based on these observations, we propose that ADH5 is a novel
      suppressor of neuronal differentiation and maturation. Inhibition of ADH5 may
      improve adult neurogenesis in a physiological or pathological setting. 

PMID- 24895130
TI  - Novel function of the Fanconi anemia group J or RECQ1 helicase to disrupt protein
      DNA complexes in a replication protein A-stimulated manner.
AB  - Understanding how cellular machinery deals with chromosomal genome complexity is
      an important question because protein bound to DNA may affect various cellular
      processes of nucleic acid metabolism. DNA helicases are at the forefront of such
      processes, yet there is only limited knowledge how they remodel protein-DNA
      complexes and how these mechanisms are regulated. We have determined that
      representative human RecQ and Fe-S cluster DNA helicases are potently blocked by
      a protein-DNA interaction. The Fanconi anemia group J (FANCJ) helicase partners
      with the single-stranded DNA-binding protein replication protein A (RPA) to
      displace BamHI-E111A bound to duplex DNA in a specific manner. Protein
      displacement was dependent on the ATPase-driven function of the helicase and
      unique properties of RPA. Further biochemical studies demonstrated that the
      shelterin proteins TRF1 and TRF2, which preferentially bind the telomeric repeat
      found at chromosome ends, effectively block FANCJ from unwinding the forked
      duplex telomeric substrate. RPA, but not the Escherichia coli single-stranded DNA
      binding protein or shelterin factor Pot1, stimulated FANCJ ejection of TRF1 from
      the telomeric DNA substrate. FANCJ was also able to displace TRF2 from the
      telomeric substrate in an RPA-dependent manner. The stimulation of helicase
      catalyzed protein displacement is also observed with the DNA helicase RECQ1,
      suggesting a conserved functional interaction of RPA-interacting helicases. These
      findings suggest that partnerships between RPA and interacting human DNA
      helicases may greatly enhance their ability to dislodge proteins bound to duplex
      DNA, an activity that is likely to be highly relevant to their biological roles
      in DNA metabolism. 

PMID- 24895132
TI  - Regulation of Plasmodium falciparum development by calcium-dependent protein
      kinase 7 (PfCDPK7).
AB  - Second messengers such as phosphoinositides and calcium are known to control
      diverse processes involved in the development of malaria parasites. However, the
      underlying molecular mechanisms and pathways need to be unraveled, which may be
      achieved by understanding the regulation of effectors of these second messengers.
      Calcium-dependent protein kinase (CDPK) family members regulate diverse parasitic
      processes. Because CDPKs are absent from the host, these kinases are considered
      as potential drug targets. We have dissected the function of an atypical CDPK
      from Plasmodium falciparum, PfCDPK7. The domain architecture of PfCDPK7 is very
      different from that of other CDPKs; it has a pleckstrin homology domain adjacent
      to the kinase domain and two calcium-binding EF-hands at its N terminus. We
      demonstrate that PfCDPK7 interacts with PI(4,5)P2 via its pleckstrin homology
      domain, which may guide its subcellular localization. Disruption of PfCDPK7
      caused a marked reduction in the growth of the blood stage parasites, as
      maturation of rings to trophozoites was markedly stalled. In addition, parasite
      proliferation was significantly attenuated. These findings shed light on an
      important role for PfCDPK7 in the erythrocytic asexual cycle of malaria
      parasites. 

PMID- 24895133
TI  - Differential role of HAMP-like linkers in regulating the functionality of the
      group III histidine kinase DhNik1p.
AB  - Nik1 orthologs are sensor kinases that function upstream of the high osmolarity
      glycerol/p38 MAPK pathway in fungi. They contain a poly-HAMP module at their N
      terminus, which plays a pivotal role in osmosensing as well as fungal death upon
      exposure to fludioxonil. DhNik1p is a typical member of this class that contains
      five HAMP domains and four HAMP-like linkers. We investigated the contribution of
      each of the HAMP-like linker regions to the functionality of DhNik1p and found
      that the HAMP4b linker was essential as its deletion resulted in the complete
      loss of activity. Replacement of this linker with flexible peptide sequences did
      not restore DhNik1p activity. Thus, the HAMP-like sequence and possibly
      structural features of this linker region are indispensable for the kinase
      activity of DhNik1p. To gain insight into the global shape of the poly-HAMP
      module in DhNik1p (HAMP1-5), multi-angle laser light and small angle x-ray
      scattering studies were carried out. Those data demonstrate that the maltose
      binding protein-tagged HAMP1-5 protein exist as a dimer in solution with an
      elongated shape of maximum linear dimension ~365 A. Placement of a sequence
      similarity based model of the HAMP1-5 protein inside experimental data-based
      models showed how two chains of HAMP1-5 are entwined on each other and the
      overall structure retained a periodicity. Normal mode analysis of the structural
      model is consistent with the H4b linker being a key to native-like collective
      motion in the protein. Overall, our shape-function studies reveal how different
      elements in the HAMP1-5 structure mediate its function.

PMID- 24895136
TI  - Beliefs, perceptions and behaviours of GPs towards generic medicines.
AB  - BACKGROUND: To benefit from cost-savings associated with generic medicine use; in
      June 2013, Ireland introduced generic substitution and reference pricing. The
      attitudes and behaviours of health care professionals may influence successful
      implementation of such changes. OBJECTIVES: To assess perceptions of GPs in
      Ireland regarding generic medicines in the time leading up to the enactment of
      the new legislation and for the first time in at least the prior decade. METHODS:
      Detailed one-to-one semi-structured interviews performed with a representative
      cohort of 34 urban- and rural-based GPs in Ireland. RESULTS: Thirty of the
      participating 34 GPs prescribed generic medicines actively. Predominantly,
      participants believed that generics worked as effectively, and were of the same
      quality, as originator medicines. However, 32 GPs reported receiving patient
      complaints regarding generics; almost a third reported complaints of increased or
      altered side effects. Thirty-two GPs stated that they would take a generic
      medicine, although one in seven would choose the originator if offered a choice.
      A minority of GPs were of the view that generics are manufactured to a poorer
      quality than originators and may be a risk to patient safety. CONCLUSION: This
      study of GPs' attitudes towards generic medicines in Ireland highlights that this
      key stakeholder group has generally positive attitudes towards both generic
      medicines and the new legislation. However, variable knowledge about generic
      medicines and concerns regarding patient experience, clinical effectiveness and
      manufacturing quality were identified. GPs' opinions could negatively influence
      patient opinions; enhancing such opinions may prove important in successfully
      implementing the new legislation.

PMID- 24895134
TI  - Small GTPase Rab17 regulates the surface expression of kainate receptors but not
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in
      hippocampal neurons via dendritic trafficking of Syntaxin-4 protein.
AB  - Glutamate receptors are fundamental for control synaptic transmission, synaptic
      plasticity, and neuronal excitability. However, many of the molecular mechanisms
      underlying their trafficking remain elusive. We previously demonstrated that the
      small GTPase Rab17 regulates dendritic trafficking in hippocampal neurons. Here,
      we investigated the role(s) of Rab17 in AMPA receptor (AMPAR) and kainate
      receptor (KAR) trafficking. Although Rab17 knockdown did not affect surface
      expression of the AMPAR subunit GluA1 under basal or chemically induced long term
      potentiation conditions, it significantly reduced surface expression of the KAR
      subunit GluK2. Rab17 co-localizes with Syntaxin-4 in the soma, dendritic shaft,
      the tips of developing hippocampal neurons, and in spines. Rab17 knockdown caused
      Syntaxin-4 redistribution away from dendrites and into axons in developing
      hippocampal neurons. Syntaxin-4 knockdown reduced GluK2 but had no effect on
      GluA1 surface expression. Moreover, overexpression of constitutively active Rab17
      promoted dendritic surface expression of GluK2 by enhancing Syntaxin-4
      translocation to dendrites. These data suggest that Rab17 mediates the dendritic
      trafficking of Syntaxin-4 to selectively regulate dendritic surface insertion of
      GluK2-containing KARs in rat hippocampal neurons.

PMID- 24895135
TI  - Poly(ADP-ribose) polymerase inhibitors sensitize cancer cells to death receptor
      mediated apoptosis by enhancing death receptor expression.
AB  - Recombinant human tumor necrosis factor-alpha-related apoptosis inducing ligand
      (TRAIL), agonistic monoclonal antibodies to TRAIL receptors, and small molecule
      TRAIL receptor agonists are in various stages of preclinical and early phase
      clinical testing as potential anticancer drugs. Accordingly, there is substantial
      interest in understanding factors that affect sensitivity to these agents. In the
      present study we observed that the poly(ADP-ribose) polymerase (PARP) inhibitors
      olaparib and veliparib sensitize the myeloid leukemia cell lines ML-1 and K562,
      the ovarian cancer line PEO1, non-small cell lung cancer line A549, and a
      majority of clinical AML isolates, but not normal marrow, to TRAIL. Further
      analysis demonstrated that PARP inhibitor treatment results in activation of the
      FAS and TNFRSF10B (death receptor 5 (DR5)) promoters, increased Fas and DR5 mRNA,
      and elevated cell surface expression of these receptors in sensitized cells.
      Chromatin immunoprecipitation demonstrated enhanced binding of the transcription
      factor Sp1 to the TNFRSF10B promoter in the presence of PARP inhibitor. Knockdown
      of PARP1 or PARP2 (but not PARP3 and PARP4) not only increased expression of Fas
      and DR5 at the mRNA and protein level, but also recapitulated the sensitizing
      effects of the PARP inhibition. Conversely, Sp1 knockdown diminished the PARP
      inhibitor effects. In view of the fact that TRAIL is part of the armamentarium of
      natural killer cells, these observations identify a new facet of PARP inhibitor
      action while simultaneously providing the mechanistic underpinnings of a novel
      therapeutic combination that warrants further investigation.

PMID- 24895138
TI  - Central nervous system infection after Onyx embolisation of arterio-venous
      malformations in two paediatric patients.
AB  - BACKGROUND: Increasingly, Onyx is used for endovascular embolization of aneurysms
      and arterio-venous malformations. Although reports in the literature on the use
      of Onyx are favourable, there have been so far no reports on the central nervous
      system (CNS) infection rate after embolisation with Onyx and no recommendations
      as to the management of these infections. CASE REPORTS: We present two cases of
      paediatric patients who acquired CNS infection with Pseudomonas aeruginosa after
      Onyx embolisation of AVMs and describe their subsequent management. CONCLUSIONS:
      Presence of established infection after Onyx embolisation should be dealt with by
      removal of infected material, administration of appropriate antibiotic therapy
      and supportive treatment.

PMID- 24895137
TI  - Patient engagement strategies used for hypertension and their influence on self
      management attributes.
AB  - BACKGROUND: Several effective methods to facilitate patient self-management of
      hypertension are available in primary care. These include direct support from
      community pharmacists and general practice, and the use of home blood pressure
      (BP) monitoring. The aim of this study is to establish the prevalence of use of
      key strategies and to determine their independent relationship with patient self
      management attributes. METHODS: A survey of patients with treated hypertension
      was undertaken in 27 community pharmacies. This established recent use of BP
      monitoring and advice from health professionals. Patient awareness of BP and
      targets, appropriateness of BP targets and adherence to anti-hypertensive
      medications were assessed as indicative self-management outcomes. Predictors of
      outcomes were determined using binary logistic regression. RESULTS: Overall, 215
      surveys were returned. Two-thirds of patients were aged >65 years, and 45% had
      conditions warranting tighter BP control (<130/80 mmHg). Almost all patients
      reported monitoring of their BP in the previous year and 63% could report their
      most recent BP reading. Just 36% reported knowing a target BP, and 78% of
      reported targets were within guidelines recommendations. One-fifth (22%)
      monitored their own BP, and 15% reported non-adherence to medication. Doctors
      provided the large majority of professional advice. Self-monitoring or
      documentation of BP readings was independently associated with increased
      likelihood of BP and target BP being known. CONCLUSIONS: Regular monitoring of BP
      does not automatically translate to professional advice. Increased uptake of
      patient self-monitoring should be promoted as a means of enabling self
      management.

PMID- 24895139
TI  - Evaporative cooling of speleothem drip water.
AB  - This study describes the first use of concurrent high-precision temperature and
      drip rate monitoring to explore what controls the temperature of speleothem
      forming drip water. Two contrasting sites, one with fast transient and one with
      slow constant dripping, in a temperate semi-arid location (Wellington, NSW,
      Australia), exhibit drip water temperatures which deviate significantly from the
      cave air temperature. We confirm the hypothesis that evaporative cooling is the
      dominant, but so far unattributed, control causing significant disequilibrium
      between drip water and host rock/air temperatures. The amount of cooling is
      dependent on the drip rate, relative humidity and ventilation. Our results have
      implications for the interpretation of temperature-sensitive, speleothem climate
      proxies such as delta(18)O, cave microecology and the use of heat as a tracer in
      karst. Understanding the processes controlling the temperature of speleothem
      forming cave drip waters is vital for assessing the reliability of such deposits
      as archives of climate change. 

PMID- 24895140
TI  - Time-to-event continual reassessment method incorporating treatment cycle
      information with application to an oncology phase I trial.
AB  - Delayed dose limiting toxicities (i.e. beyond first cycle of treatment) is a
      challenge for phase I trials. The time-to-event continual reassessment method
      (TITE-CRM) is a Bayesian dose-finding design to address the issue of long
      observation time and early patient drop-out. It uses a weighted binomial
      likelihood with weights assigned to observations by the unknown time-to-toxicity
      distribution, and is open to accrual continually. To avoid dosing at overly toxic
      levels while retaining accuracy and efficiency for DLT evaluation that involves
      multiple cycles, we propose an adaptive weight function by incorporating cyclical
      data of the experimental treatment with parameters updated continually. This
      provides a reasonable estimate for the time-to-toxicity distribution by
      accounting for inter-cycle variability and maintains the statistical properties
      of consistency and coherence. A case study of a First-in-Human trial in cancer
      for an experimental biologic is presented using the proposed design. Design
      calibrations for the clinical and statistical parameters are conducted to ensure
      good operating characteristics. Simulation results show that the proposed TITE
      CRM design with adaptive weight function yields significantly shorter trial
      duration, does not expose patients to additional risk, is competitive against the
      existing weighting methods, and possesses some desirable properties. 

PMID- 24895141
TI  - Preservative-free latanoprost eye drops in patients with primary open-angle
      glaucoma/ocular hypertension.
AB  - Latanoprost is an ester prodrug prostaglandin F2alpha analogue that is a
      selective agonist of endogenous prostanoid FP receptors and that reduces
      intraocular pressure (IOP) by increasing the uveoscleral outflow of aqueous
      humour. Preservative-free (PF) latanoprost [Monoprost((r))] is a new formulation
      of latanoprost that is approved for use in the EU in patients with primary open
      angle glaucoma (POAG)/ocular hypertension. This article reviews the clinical
      pharmacology of this new formulation, focussing on its efficacy and tolerability
      in this indication. PF latanoprost was efficacious in reducing IOP in a
      randomized, investigator-masked, multinational trial in patients with POAG/ocular
      hypertension (n = 404). At days 15, 42 and 84 of follow-up, PF latanoprost was
      noninferior to benzalkonium chloride-preserved (BAK) latanoprost in terms of
      reductions in IOP. In this trial, at days 42 and 84 the proportions of patients
      with conjunctival hyperaemia were significantly lower with PF latanoprost than
      with BAK latanoprost. Patient subjective ratings of ocular symptoms were also
      significantly lower with PF latanoprost than with BAK latanoprost. In the absence
      of head-to-head comparisons with other anti-glaucoma drugs, an adjusted, indirect
      comparison meta-analysis was performed using data from 21 randomized clinical
      trials in patients with POAG/ocular hypertension. Based on this analysis, PF
      latanoprost had similar efficacy to different formulations of three comparator
      prostaglandin analogues in reducing the patient's IOP and was associated with a
      significantly lower risk of developing hyperaemia/ocular redness than these
      comparators. PF latanoprost offers a useful alternative to the available
      preserved prostaglandin analogues for the treatment of POAG/ocular hypertension.

PMID- 24895142
TI  - Aspects of emotional functioning following oesophageal cancer surgery in a
      population-based cohort study.
AB  - OBJECTIVE: The aim of this study was to establish the proportion of patients
      reporting emotional problems following oesophagectomy for cancer and identify the
      risk characteristics for emotional problems. METHODS: A Swedish population-based
      cohort study of patients with surgically treated oesophageal cancer was used. The
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire C30 was used to assess tension, worry, irritation and depressed
      mood at 6 months and 5 years after surgery. Potential risk characteristics were
      retrieved from medical notes and data linkages to Swedish health registries.
      Multivariable logistic regression analyses were performed to examine risk
      characteristics for poor emotional recovery. RESULTS: Of 401 patients included at
      6 months, 49% reported problems with tension, 61% worry, 62% irritation and 63%
      depressed mood. Of the 140 (35%) patients who completed the 5-year follow-up, 39%
      reported problems with tension and about half of the patients reported problems
      with worry, irritation, and depressed mood (49, 45 and 52%, respectively).
      Squamous cell carcinoma was identified as a risk characteristic for tension (OR
      2.15, 95% CI 1.30-3.55), worry (OR 2.02, 95% CI 1.19-3.40) and depressed mood (OR
      1.71, 95% CI 1.01-2.90) at 6 months compared with adenocarcinoma. Compared with
      higher education, lower education was associated with tension (upper secondary
      schooling: OR 1.97, 95% CI 1.02-3.79 and 9-year compulsory: OR 2.46, 95% CI 1.28
      4.74), while non-cohabitating patients were less likely to report problems with
      worry at 6 months (OR 0.53, 95% CI 0.34-0.84) compared with cohabitating
      patients. CONCLUSIONS: A substantial proportion of patients reports emotional
      problems following oesophagectomy, and risk characteristics include squamous cell
      carcinoma histology and low educational level.

PMID- 24895143
TI  - Medical acceptance of the nurse practitioner role in Australia: a decade on.
AB  - PURPOSE: In Australia, nurse practitioners (NPs) were first endorsed in 2000.
      After more than a decade, the number of NPs remains relatively small with
      previous research suggesting medical resistance as a key reason for this. This
      article presents a selection of narratives from a study that explored the
      transition experiences of newly endorsed NPs with particular attention to
      relationships with their medical colleagues. DATA SOURCES: A critical
      ethnographic approach was undertaken to explore the experiences of 10 Australian
      NPs who were interviewed three to four times for up to an hour throughout their
      first year of practice. CONCLUSIONS: Participants' narratives provide insight
      into their transition to practice and the barriers and facilitators to their new
      role. In contrast to previous research, medical colleagues were generally
      supportive and collegial while resistance was demonstrated most often by senior
      nurses yielding positions of power. IMPLICATIONS FOR PRACTICE: This study
      provides insight into the influences that key health professionals have over the
      transition of NPs. Despite the fact there are still negative attitudes being
      expressed by some medical associations, in this study medical colleagues were
      largely supportive of the NP role and that integral to the development of these
      interprofessional relationships was mutual respect and effective communication.

PMID- 24895144
TI  - Exposure vs. response of blood pressure in patients with rheumatoid arthritis
      following treatment with fostamatinib.
AB  - Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor which has been
      evaluated as a potential treatment for rheumatoid arthritis (RA). Treatment with
      fostamatinib has been associated with an increase in blood pressure (BP). In this
      work, we present a pooled analysis of the pharmacokinetic-pharmacodynamic (PKPD)
      relationship for BP, based on 3 Phase III studies, aiming to increase the
      knowledge about fostamatinib's effect on BP in the RA population. Fostamatinib is
      rapidly and extensively converted to R406 after oral administration of
      fostamatinib, and the PK of R406 could be described by a two-compartment
      population PK model with first order absorption, with an estimated CL/F of 18.7
      L/h. Average steady-state concentrations, predicted based on the individual CL/F
      estimates, were subsequently used in the PKPD analysis. The population PKPD
      analysis revealed a concentration dependent increase of BP with increasing R406
      concentrations, where a power model and an Emax model best described the increase
      in SBP and DBP, respectively. The predicted increases were +5.2 mmHg for SBP and
      +4.2 mmHg for DBP, for a 100 mg bid dose. The impact of covariates on the PKPD
      relationship was investigated but covariates did only explain a minor part of the
      overall high variability in BP. 

PMID- 24895145
TI  - Development of a rebamipide solid dispersion system with improved dissolution and
      oral bioavailability.
AB  - The purpose of this study was to improve the gastric solubility and
      bioavailability of rebamipide (RBM) by preparing the RBM solid dispersion tablet
      (RBM-SDT) from solid dispersion powder prepared by spray-drying technique. For
      preparation of rebamipide solid dispersions (RBM-SDs), solubility study was
      performed in various hydrophilic carriers and alkalizers, among which sodium
      alginate and sodium carbonate were selected as the hydrophilic polymer and
      alkalizer, respectively. Different combinations of drug-polymer-alkalizer were
      dissolved in aqueous solution and spray-dried in order to obtain solid
      dispersions. Noticeable improvement in aqueous solubility (approximately 200
      times) and in vitro dissolution rate was observed by RBM-SDs, compared to RBM
      powder. The optimized formulation of RBM-SD powder consisted of RBM powder/sodium
      alginate/sodium carbonate at the weight ratio of 1/2/2. The transformation of
      crystalline RBM to amorphous RBM-SD powder was clearly demonstrated by powder X
      ray diffraction, differential scanning calorimetry (DSC) and scanning electron
      microscopy. The optimized RBM-SD was formulated in tablet dosage form, containing
      approximately 2 % sodium lauryl sulphate and poloxamer F68 as wetting agents. The
      RBM-SDT exhibited enhanced dissolution in hydrochloric acid buffer (pH 1.2) and
      distilled water. Moreover, pharmacokinetic study in rats showed higher AUC and
      Cmax for RBM-SDT than those for RBM powder and commercial product. Thus, the
      developed RBM-SDT formulation can be more efficacious for improving oral
      bioavailability of RBM. 

PMID- 24895147
TI  - Sustained-release formulation of sarpogrelate hydrochloride.
AB  - Sarpogrelate HCl (SGL) has been used clinically as an anti-platelet drug for the
      prevention of thrombus, proliferation of vascular smooth muscle cells and
      platelet aggregation. This study was to investigate the bioavailability of
      sustained-release solid dispersion (SR-SD) formulation of SGL to sustain the drug
      release for up to 24 h. The SR-SD formulations with various drug-to-polymer
      ratios were prepared by hot-melt coating method. Waxy material carriers such as
      Compritol 888 ATO and stearyl alcohol were added to SGL and different amounts of
      HPMC K 15 (HPMC) were mixed. Dissolution profile and bioavailability were
      compared to SGL powder. Compritol 888 ATO showed the controlling effect of the
      initial release rate of drug from the formulation and the controlling effect was
      increased for 24 h by addition of HPMC. As the amount of HPMC increased, the drug
      release rate from SR-SD decreased because HPMC formed gel layer in aqueous media.
      Pharmacokinetic study showed that the AUC and Tmax of SGL in SR-SD formulation
      increased as compared to the SGL powder. These data suggest that the SR-SD
      formulation effectively controls the drug release rate for 24 h, hoping to be
      useful for the development of once-a-day formulation of SGL. 

PMID- 24895148
TI  - Coffee time is about much more than coffee.

PMID- 24895146
TI  - Differential effects of quercetin glycosides on GABAC receptor channel activity.
AB  - Quercetin, a representative flavonoid, is a compound of low molecular weight
      found in various colored plants and vegetables. Quercetin shows a wide range of
      neuropharmacological activities. In fact, quercetin naturally exists as monomer
      (quercetin-3-O-rhamnoside) (Rham1), dimer-(Rutin), or trimer-glycosides
      [quercetin-3-(2(G)-rhamnosylrutinoside)] (Rham2) at carbon-3 in fruits and
      vegetables. The carbohydrate components are removed after ingestion into
      gastrointestinal systems. The role of the glycosides attached to quercetin in the
      regulation of gamma-aminobutyric acid class C (GABAC) receptor channel activity
      has not been determined. In the present study, we examined the effects of
      quercetin glycosides on GABAC receptor channel activity by expressing human GABAC
      alone in Xenopus oocytes using a two-electrode voltage clamp technique and also
      compared the effects of quercetin glycosides with quercetin. We found that GABA
      induced inward current (I GABA ) was inhibited by quercetin or quercetin
      glycosides. The inhibitory effects of quercetin and its glycosides on I GABA were
      concentration-dependent and reversible in the order of Rutin ~ quercetin ~ Rham 1
      > Rham 2. The inhibitory effects of quercetin and its glycosides on I GABA were
      noncompetitive and membrane voltage-insensitive. These results indicate that
      quercetin and its glycosides regulate GABAC receptor channel activity through
      interaction with a different site from that of GABA, and that the number of
      carbohydrate attached to quercetin might play an important role in the regulation
      of GABAC receptor channel activity. 

PMID- 24895150
TI  - Development of tissue-engineered self-expandable aortic stent grafts (Bio stent
      grafts) using in-body tissue architecture technology in beagles.
AB  - In this study, we aimed to describe the development of tissue-engineered self
      expandable aortic stent grafts (Bio stent graft) using in-body tissue
      architecture technology in beagles and to determine its mechanical and
      histological properties. The preparation mold was assembled by insertion of an
      acryl rod (outer diameter, 8.6 mm; length, 40 mm) into a self-expanding nitinol
      stent (internal diameter, 9.0 mm; length, 35 mm). The molds (n = 6) were embedded
      into the subcutaneous pouches of three beagles for 4 weeks. After harvesting and
      removing each rod, the excessive fragile tissue connected around the molds was
      trimmed, and thus tubular autologous connective tissues with the stent were
      obtained for use as Bio stent grafts (outer diameter, approximately 9.3 mm in all
      molds). The stent strut was completely surrounded by the dense collagenous
      membrane (thickness, ~150 um). The Bio stent graft luminal surface was extremely
      flat and smooth. The graft wall of the Bio stent graft possessed an elastic
      modulus that was almost two times higher than that of the native beagle abdominal
      aorta. This Bio stent graft is expected to exhibit excellent biocompatibility
      after being implanted in the aorta, which may reduce the risk of type 1 endoleaks
      or migration.

PMID- 24895149
TI  - Temporal changes in serum biomarkers and risk for progression of gastric
      precancerous lesions: a longitudinal study.
AB  - Effectively managing precancerous lesions is crucial to reducing the gastric
      cancer (GC) burden. We evaluated associations of temporal changes in multiple
      serological markers (pepsinogen I [PGI], PGII, PGI/II ratio, gastrin-17 and anti
      Helicobacter pylori IgG) with risk for progression of gastric precancerous
      lesions. From 1997 to 2011, repeated esophagogastroduodenoscopies with gastric
      mucosal biopsies and blood sample collections were conducted on 2,039
      participants (5,070 person-visits) in the Zhuanghe Gastric Diseases Screening
      Program, Liaoning, China. Serum biomarkers were measured using ELISA, and gastric
      biopsies were evaluated using standardized histologic criteria. Odds ratios (OR)
      and 95% confidence intervals (CI) were estimated using generalized estimating
      equations for correlated binary outcomes. The ORs for progression of gastric
      conditions comparing those whose serum PGI, PGII, and anti-H. pylori IgG levels
      increased >= 50% relative to those whose decreased >= 50% were, respectively 1.67
      (CI, 1.22-2.28), 1.80 (CI, 1.40-2.33) and 1.93 (CI, 1.48-2.52). The OR for those
      whose PGI/II ratio decreased >= 50% relative to those whose increased >= 50% was
      1.40 (CI, 1.08-1.81), and for those whose PGII and anti-H. pylori IgG levels both
      increased >= 50% relative to those whose levels both decreased >= 50% the OR was
      3.18 (CI, 2.05-4.93). Changes in gastrin-17 were not statistically significantly
      associated with progression. These findings suggest that temporal changes in
      serum PGI, PGII, PGI/II ratio, and anti-H. pylori IgG levels (especially PGII and
      anti-H. pylori IgG combined) may be useful for assessing and managing risk for
      progression of gastric precancerous lesions.

PMID- 24895151
TI  - P1PK, GLOB, and FORS blood group systems and GLOB collection: biochemical and
      clinical aspects. Do we understand it all yet?
AB  - Antigens belonging to the P1PK, GLOB, and FORS blood group systems and the GLOB
      blood group collection represent a closely related set of 13 glycosphingolipids
      (GSLs). They are synthesized by the coordinated action of glycosyltransferases,
      encoded by at least 7 different loci. Three of these enzymes show either
      different activity or a different mRNA expression profile due to genetic
      polymorphisms, resulting in blood group diversity. In recent years, significant
      progress has been made in understanding the molecular background and biological
      functions of these GSLs. Their medical significance is often related to the
      existence of natural antibodies, as they may cause complications after
      transfusions and during pregnancies. In addition, GSLs belonging to these blood
      group systems are receptors for several pathogens. This review summarizes the
      present knowledge about the complicated network of enzymatic interactions leading
      to synthesis of these GSLs, as well as their clinical implications. 

PMID- 24895152
TI  - Peptide p160-coated silica nanoparticles applied in photodynamic therapy.
AB  - Peptide p160-conjugated mesoporous silica nanoparticles (MSN) were fabricated and
      loaded with photosensitizer hypocrellin B (HB). The results indicate that the
      nanocomposites have better selectivity for cancer cells and higher cytotoxicity
      in photodynamic therapy in vitro. The nanocomposites can be used as a novel
      candidate in photodynamic therapy. This may be a general and promising method to
      modify nanoparticles to improve their cell affinity. 

PMID- 24895153
TI  - Hydride-rhodium(III)-N-heterocyclic carbene catalysts for vinyl-selective H/D
      exchange: a structure-activity study.
AB  - A series of neutral and cationic Rh(III) -hydride and Rh(III) -ethyl complexes
      bearing a NHC ligand has been synthesized and evaluated as catalyst precursors
      for H/D exchange of styrene using CD(3)OD as a deuterium source. Various ligands
      have been examined in order to understand how the stereoelectronic properties can
      modulate the catalytic activity. Most of these complexes proved to be very active
      and selective in the vinylic H/D exchange, without deuteration at the aromatic
      positions, displaying very high selectivity toward the beta-positions. In
      particular, the cationic complex [RhClH(CH(3)CN)(3)(IPr)]CF(3)SO(3) showed
      excellent catalytic activity, reaching the maximum attainable degree of beta
      vinylic deuteration in only 20 min. By modulation of the catalyst structure, we
      obtained improved alpha/beta selectivity. Thus, the catalyst [RhClH(kappa(2)-O,N
      C(9)H(6)NO)(SIPr)], bearing an 8-quinolinolate ligand and a bulky and strongly
      electron-donating SIPr as the NHC, showed total selectivity for the beta-vinylic
      positions. This systematic study has shown that increased electron density and
      steric demand at the metal center can improve both the catalytic activity and
      selectivity. Complexes bearing ligands with very high steric hindrance, however,
      proved to be inactive.

PMID- 24895154
TI  - Effect of covariate omission in Weibull accelerated failure time model: a
      caution.
AB  - The accelerated failure time model is presented as an alternative to the
      proportional hazard model in the analysis of survival data. We investigate the
      effect of covariates omission in the case of applying a Weibull accelerated
      failure time model. In an uncensored setting, the asymptotic bias of the
      treatment effect is theoretically zero when important covariates are omitted;
      however, the asymptotic variance estimator of the treatment effect could be
      biased and then the size of the Wald test for the treatment effect is likely to
      exceed the nominal level. In some cases, the test size could be more than twice
      the nominal level. In a simulation study, in both censored and uncensored
      settings, Type I error for the test of the treatment effect was likely inflated
      when the prognostic covariates are omitted. This work remarks the careless use of
      the accelerated failure time model. We recommend the use of the robust sandwich
      variance estimator in order to avoid the inflation of the Type I error in the
      accelerated failure time model, although the robust variance is not commonly used
      in the survival data analyses. 

PMID- 24895156
TI  - The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields
      bone growth stimulation in acute fractures: a systematic review and meta-analysis
      of randomized controlled trials.
AB  - INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate
      the best currently available evidence from randomized controlled trials comparing
      pulsed electromagnetic fields (PEMF) or low-intensity pulsed ultrasound (LIPUS)
      bone growth stimulation with placebo for acute fractures. MATERIALS AND METHODS:
      We performed a systematic literature search of the medical literature from 1980
      to 2013 for randomized clinical trials concerning acute fractures in adults
      treated with PEMF or LIPUS. Two reviewers independently determined the strength
      of the included studies by assessing the risk of bias according to the criteria
      in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Seven
      hundred and thirty-seven patients from 13 trials were included. Pooled results
      from 13 trials reporting proportion of nonunion showed no significant difference
      between PEMF or LIPUS and control. With regard to time to radiological union, we
      found heterogeneous results that significantly favoured PEMF or LIPUS bone growth
      stimulation only in non-operatively treated fractures or fractures of the upper
      limb. Furthermore, we found significant results that suggest that the use of PEMF
      or LIPUS in acute diaphyseal fractures may accelerate the time to clinical union.
      CONCLUSIONS: Current evidence from randomized trials is insufficient to conclude
      a benefit of PEMF or LIPUS bone growth stimulation in reducing the incidence of
      nonunions when used for treatment in acute fractures. However, our systematic
      review and meta-analysis suggest that PEMF or LIPUS can be beneficial in the
      treatment of acute fractures regarding time to radiological and clinical union.
      PEMF and LIPUS significantly shorten time to radiological union for acute
      fractures undergoing non-operative treatment and acute fractures of the upper
      limb. Furthermore, PEMF or LIPUS bone growth stimulation accelerates the time to
      clinical union for acute diaphyseal fractures.

PMID- 24895155
TI  - Probing protonation sites of isolated flavins using IR spectroscopy: from
      lumichrome to the cofactor flavin mononucleotide.
AB  - Infrared spectra of the isolated protonated flavin molecules lumichrome,
      lumiflavin, riboflavin (vitamin B2), and the biologically important cofactor
      flavin mononucleotide are measured in the fingerprint region (600-1850 cm(-1)) by
      means of IR multiple-photon dissociation (IRMPD) spectroscopy. Using density
      functional theory calculations, the geometries, relative energies, and linear IR
      absorption spectra of several low-energy isomers are calculated. Comparison of
      the calculated IR spectra with the measured IRMPD spectra reveals that the N10
      substituent on the isoalloxazine ring influences the protonation site of the
      flavin. Lumichrome, with a hydrogen substituent, is only stable as the N1
      protonated tautomer and protonates at N5 of the pyrazine ring. The presence of
      the ribityl unit in riboflavin leads to protonation at N1 of the pyrimidinedione
      moiety, and methyl substitution in lumiflavin stabilizes the tautomer that is
      protonated at O2. In contrast, flavin mononucleotide exists as both the O2- and
      N1-protonated tautomers. The frequencies and relative intensities of the two C=O
      stretch vibrations in protonated flavins serve as reliable indicators for their
      protonation site.

PMID- 24895157
TI  - Perirenal myelolipoma diagnosed on imprint: case report and review of the
      literature.
AB  - Myelolipomas are benign tumors containing adipose tissue and hematopoeitic
      elements which occur most commonly in the adrenal glands. Extra-adrenal
      myelolipomas are uncommon with few cases of renal and perirenal myelolipomas in
      the literature. These cases may be difficult to diagnose based on radiology alone
      and intraoperative diagnosis can be extremely important in determining the course
      of surgery. Due to the lipomatous component of the tumor it may be technically
      difficult to prepare adequate frozen sections; this problem can be obviated by
      utilization of cytologic imprint preparations. We present a case of perirenal
      myelolipoma diagnosed intraoperatively utilizing cytologic imprint preparations
      stained with toluidine blue and hematoxylin and eosin.

PMID- 24895158
TI  - Atypical antipsychotics olanzapine, quetiapine, and risperidone and risk of acute
      major cardiovascular events in young and middle-aged adults: a nationwide
      register-based cohort study in Denmark.
AB  - BACKGROUND: A number of serious cardiovascular safety concerns related to the use
      of atypical antipsychotics, compared with no use, have emerged, but nearly all
      reports are from studies of older patients. We aimed to compare the risk of
      cardiovascular events between the three most commonly used atypical
      antipsychotics in young and middle-aged adults. METHODS: We conducted a
      nationwide register-based cohort study in Denmark, 1997-2011, including adults
      aged 18-64 years, who started treatment with oral or intramuscular olanzapine (n
      = 15,774), oral quetiapine (n = 18,717), and oral or intramuscular risperidone (n
      = 14,134). The primary outcome was any major cardiovascular event (composite of
      cardiovascular mortality, acute coronary syndrome, or ischemic stroke) within 1
      year following treatment initiation. Cox regression was used to estimate hazard
      ratios (HRs) while on current antipsychotic monotherapy in the outpatient
      setting, adjusting for an outcome-specific disease risk score. RESULTS: The crude
      rate of any major cardiovascular event was 5.3 per 1,000 person-years among
      olanzapine users, 3.4 in quetiapine users, and 5.2 in risperidone users. Compared
      with risperidone, the risk of any major cardiovascular event was not
      significantly different in olanzapine users (HR 0.90, 95 % confidence interval
      [CI] 0.53-1.52) and quetiapine users (HR 0.79, 95 % CI 0.45-1.39). The absolute
      risk difference per 1,000 person-years on treatment was -0.5 (95 % CI -2.4 to
      2.7) events for olanzapine and -1.1 (95 % CI -2.9 to 2.0) events for quetiapine.
      CONCLUSIONS: Among young and middle-aged outpatients, the risk of acute major
      cardiovascular events was similar with use of olanzapine, quetiapine, and
      risperidone. Although moderate relative differences cannot be ruled out, any
      differences are small in absolute terms.

PMID- 24895159
TI  - Risk factors associated with cerebrovascular recurrence in symptomatic carotid
      disease: a comparative study of carotid plaque morphology, microemboli assessment
      and the European Carotid Surgery Trial risk model.
AB  - BACKGROUND: The European Carotid Surgery Trial (ECST) risk model is a validated
      tool for predicting cerebrovascular risk in patients with symptomatic carotid
      disease. Carotid plaque hemorrhage as detected by MRI (MRIPH) and microembolic
      signals (MES) detected by transcranial Doppler (TCD) are 2 emerging modalities in
      assessing instability of the carotid plaque. The aim of this study was to assess
      the strength of association of MES and MRIPH with cerebrovascular recurrence in
      patients with symptomatic carotid artery disease in comparison with the ECST risk
      prediction model. METHODS AND RESULTS: One hundred and thirty-four prospectively
      recruited patients (mean [SD]: age 72 [9.8] years, 33% female) with symptomatic
      severe (50% to 99%) carotid stenosis underwent preoperative TCD, MRI of the
      carotid arteries to assess MES, PH, and the ECST risk model. Patients were
      followed up until carotid endarterectomy, recurrent cerebral event, death, or
      study end. Event-free survival analysis was done using backward conditional Cox
      regression analysis.Of the 123 patients who had both TCD and MRI, 82 (66.7%)
      demonstrated PH and 46 (37.4%) had MES. 37 (30.1%) cerebrovascular events (21
      transient ischemic attacks, 6 amaurosis fugax, and 10 strokes) were observed.
      Both carotid PH (HR=8.68; 95% CI 2.66 to 28.40, P<0.001) as well as MES (HR=3.28;
      95% CI 1.68 to 6.42, P=0.001) were associated with cerebrovascular event
      recurrence. Combining MES and MRIPH improved the strength of association
      (HR=0.74, 95% CI 0.65 to 0.83; P<0.001). The ECST risk model was not associated
      with recurrence (HR=0.86; 95% CI 0.45 to 1.65; P=0.65). CONCLUSIONS: The presence
      of carotid plaque hemorrhage is better associated with recurrent cerebrovascular
      events in patients with symptomatic severe carotid stenosis than the presence of
      microembolic signals; combining MES and MRIPH, further improves the association
      while the ECST risk score was insignificant.

PMID- 24895160
TI  - Protein changes contributing to right ventricular cardiomyocyte diastolic
      dysfunction in pulmonary arterial hypertension.
AB  - BACKGROUND: Right ventricular (RV) diastolic function is impaired in patients
      with pulmonary arterial hypertension (PAH). Our previous study showed that
      elevated cardiomyocyte stiffness and myofilament Ca(2+) sensitivity underlie
      diastolic dysfunction in PAH. This study investigates protein modifications
      contributing to cellular diastolic dysfunction in PAH. METHODS AND RESULTS: RV
      samples from PAH patients undergoing heart-lung transplantation were compared to
      non-failing donors (Don). Titin stiffness contribution to RV diastolic
      dysfunction was determined by Western-blot analyses using antibodies to protein
      kinase-A (PKA), Calpha (PKCalpha) and Ca(2+)/calmoduling-dependent-kinase
      (CamKIIdelta) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469),
      PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKCalpha sites
      were significantly less phosphorylated in PAH compared with donors (P<0.0001). To
      test the functional relevance of PKA-, PKCalpha-, and CamKIIdelta-mediated titin
      phosphorylation, we measured the stiffness of single RV cardiomyocytes before and
      after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte
      diastolic stiffness, PKCalpha further increased stiffness while CamKIIdelta had
      no major effect. CamKIIdelta activation was determined indirectly by measuring
      PLN Thr17phosphorylation level. No significant changes were found between the
      groups. Myofilament Ca(2+) sensitivity is mediated by sarcomeric troponin I
      (cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH
      compared with donors (P<0.05) and reduced PKA-mediated cTnI phosphorylation
      (Ser22/23) (P<0.001). Finally, alterations in Ca(2+)-handling proteins contribute
      to RV diastolic dysfunction due to insufficient diastolic Ca(2+) clearance. PAH
      SERCA2a levels and PLN phosphorylation were significantly reduced compared with
      donors (P<0.05). CONCLUSIONS: Increased titin stiffness, reduced cTnI
      phosphorylation, and altered levels of phosphorylation of Ca(2+) handling
      proteins contribute to RV diastolic dysfunction in PAH.

PMID- 24895161
TI  - Atrial fibrillation, stroke, and anticoagulation in Medicare beneficiaries:
      trends by age, sex, and race, 1992-2010.
AB  - BACKGROUND: We evaluated temporal trends in ischemic stroke and warfarin use
      among demographic subsets of the US Medicare population that are not well
      represented in randomized trials of warfarin for stroke prevention in nonvalvular
      atrial fibrillation (AF). METHODS AND RESULTS: One-year cohorts of Medicare
      primary payer patients (1992-2010) were created using the Medicare 5% sample.
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes were used to identify AF and ischemic and hemorrhagic stroke; >= 3
      consecutive prothrombin time claims were used to identify warfarin use. Ischemic
      stroke rates (per 1000 patient-years) decreased markedly from 1992 to 2010. Among
      women, rates decreased from 37.1 to 13.6 for ages 65 to 74 years, from 55.2 to
      16.5 for ages 74 to 84, and from 66.9 to 22.9 for age >= 85; warfarin use
      increased 31% to 59%, 27% to 63%, and 15% to 49%, respectively. Among men, rates
      decreased from 33.8 to 11.7 for ages 65 to 74 years, from 49.2 to 13.8 for ages
      75 to 84, and from 51.5 to 18.0 for age >= 85; warfarin use increased 34% to 63%,
      28% to 66%, and 15% to 55%, respectively. Rates decreased from 47.0 to 14.8 for
      whites and 73.0 to 29.3 for blacks; warfarin use increased 27% to 61% and 19% to
      52%, respectively. In all age categories, the thromboembolic risk (CHADS
      [congestive heart failure, hypertension, age >= 75 years, diabetes, stroke])
      score was significantly higher among women (versus men) and blacks (versus
      whites). CONCLUSIONS: Ischemic stroke rates among Medicare AF patients decreased
      significantly in all demographic subpopulations from 1992-2010, coincident with
      increasing warfarin use. Ischemic stroke rates remained higher and warfarin use
      rates remained lower for women and blacks with AF, groups whose baseline CHADS
      scores were higher.

PMID- 24895162
TI  - Decreased myocardial dendritic cells is associated with impaired reparative
      fibrosis and development of cardiac rupture after myocardial infarction in
      humans.
AB  - BACKGROUND: Dendritic cells (DC) play pivotal roles in regulating the immune
      system and inflammatory response. We previously reported DC infiltration in the
      infarcted heart and its immunoprotective roles in the post-infarction healing
      process after experimental myocardial infarction (MI). However, its clinical
      significance has not been determined. METHODS AND RESULTS: The degree of DC
      infiltration and its correlation with the post-infarction healing process in the
      human infarcted heart were investigated in 24 autopsy subjects after ST-elevation
      MI. Patients were divided into two groups according to the presence (n=13) or
      absence (n=11) of cardiac rupture. The numbers of infiltrated DC and macrophages
      and the extent of fibrosis in the infarcted area were examined. In the rupture
      group, CD68(+) macrophage infiltration was increased and CD209(+) DC, and
      CD11c(+) DC infiltration and the extent of reparative fibrosis were decreased
      compared with the non-rupture group, under matched baseline characteristics
      including the time from onset to death and use of revascularization. Furthermore,
      there was a significant positive correlation between the number of infiltrating
      CD209(+) DC, and CD11c(+) DC and the extent of reparative fibrosis. CONCLUSIONS:
      Decreased number of DC in human-infarcted myocardial tissue was associated with
      increased macrophage infiltration, impaired reparative fibrosis, and the
      development of cardiac rupture after MI. These findings suggest a protective role
      of DC in post-MI inflammation and the subsequent healing process.

PMID- 24895163
TI  - Postextrasystolic blood pressure potentiation predicts poor outcome of cardiac
      patients.
AB  - BACKGROUND: Postextrasystolic blood pressure potentiation (PESP), the pulse wave
      augmentation after an extrasystolic beat, is typically enhanced in heart failure
      (HF) patients. This study prospectively tested the association of PESP and
      mortality in cardiac patients. METHODS AND RESULTS: Consecutive patients (n=941;
      mean age, 61 years; 19% female) presenting with acute myocardial infarction were
      enrolled between May 2000 and March 2005 and followed up until August 2010. The
      main study outcome was 5-year all-cause mortality. Patients underwent noninvasive
      30-minute recordings of ECG and continuous blood pressure. PESP presence was
      based on the ratio between the first postectopic pulse wave amplitude and the
      mean of the subsequent 9 pulse wave amplitudes. A ratio above 1 was prospectively
      defined as PESP present. Ventricular premature complexes (VPCs) suitable for PESP
      quantification were present in recordings of 220 patients. PESP was present in 62
      of these patients. Patients without suitable VPCs were classified as PESP
      absent.During the follow-up, 72 patients died. Among the 220 patients in whom
      PESP was measurable, 27 died. Under univariable analysis, PESP was a significant
      predictor of death (P<0.001) as were GRACE score (P<0.001), left ventricular
      ejection fraction (LVEF) (P<0.001), and the number of recorded VPCs (P<0.001).
      Under multivariable analysis, PESP (P<0.001), GRACE score (P<0.001), and LVEF
      (P=0.001) were independently associated with outcome. The combination of PESP
      presence and LVEF <= 35% identified a subgroup of patients with a particularly
      high mortality of 46.7%. Separate validation reproduced the finding in an
      unrelated population of 146 HF patients. CONCLUSIONS: PESP, which likely reflects
      abnormalities of myocardial calcium cycling, predicts the mortality risk in
      postinfarction patients. CLINICAL TRIAL REGISTRATION URL: ClinicalTrials.gov.
      Unique identifier: NCT00196274.

PMID- 24895164
TI  - Functional analysis of the TRIB1 associated locus linked to plasma triglycerides
      and coronary artery disease.
AB  - BACKGROUND: The TRIB1 locus has been linked to hepatic triglyceride metabolism in
      mice and to plasma triglycerides and coronary artery disease in humans. The lipid
      associated single nucleotide polymorphisms (SNPs), identified by genome-wide
      association studies, are located ~30 kb downstream from TRIB1, suggesting complex
      regulatory effects on genes or pathways relevant to hepatic triglyceride
      metabolism. The goal of this study was to investigate the functional relationship
      between common SNPs at the TRIB1 locus and plasma lipid traits. METHODS AND
      RESULTS: Characterization of the risk locus reveals that it encompasses a gene,
      TRIB1-associated locus (TRIBAL), composed of a well-conserved promoter region and
      an alternatively spliced transcript. Bioinformatic analysis and resequencing
      identified a single SNP, rs2001844, within the promoter region that associates
      with increased plasma triglycerides and reduced high-density lipoprotein
      cholesterol and coronary artery disease risk. Further, correction for
      triglycerides as a covariate indicated that the genome-wide association studies
      association is largely dependent on triglycerides. In addition, we show that
      rs2001844 is an expression trait locus (eQTL) for TRIB1 expression in blood and
      alters TRIBAL promoter activity in a reporter assay model. The TRIBAL transcript
      has features typical of long noncoding RNAs, including poor sequence
      conservation. Modulation of TRIBAL expression had limited impact on either TRIB1
      or lipid regulatory genes mRNA levels in human hepatocyte models. In contrast,
      TRIB1 knockdown markedly increased TRIBAL expression in HepG2 cells and primary
      human hepatocytes. CONCLUSIONS: These studies demonstrate an interplay between a
      novel locus, TRIBAL, and TRIB1. TRIBAL is located in the genome-wide association
      studies identified risk locus, responds to altered expression of TRIB1, harbors a
      risk SNP that is an eQTL for TRIB1 expression, and associates with plasma
      triglyceride concentrations.

PMID- 24895165
TI  - Prognostic power of mitral annulus indices of left ventricular diastolic
      function.

PMID- 24895167
TI  - CD10 expression is enhanced by Twist1 and associated with poor prognosis in
      esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro and
      in vivo.
AB  - CD10 expression was identified as a contributor to cancer progression in several
      cancers; however, the exact biological significance and mechanism of CD10
      expression remains unclear. In addition, CD10 expression in esophageal squamous
      cell carcinoma (ESCC) has not been studied. We investigated the relationship
      between CD10 and Twist1. Furthermore, we examined the effect of CD10 on
      tumorigenicity using in vivo and in vitro systems as well as establishing the
      clinical significance of CD10 expression in ESCC using large clinical samples.
      CD10 expression was upregulated by Twist1 and there was a strong correlation
      between mRNA and protein expression. Twist1 can specifically upregulate CD10 at
      the transcriptional level via an interaction with the promoter region of CD10 and
      the proximal E-box CAGGTG in the CD10 promoter was identified as a binding site
      for Twist1. CD10 is frequently expressed in ESCC cell lines and silencing CD10
      suppresses migration/invasion and anchorage-independent tumor growth of ESCC
      cells. Knockdown of CD10 inhibits the growth of ESCC xenograft in nude mice,
      suggesting that CD10 plays a role in enhancing the tumorigenesis of ESCC. From
      among 153 ESCC samples, 46 (30.0%) showed varying degrees of CD10 expression in
      cancer cells. In addition, stromal fibroblasts also showed varying amounts of
      CD10 expression in 92 (60.9%) tumor samples. CD10 overexpression in cancer cells
      as well as in stromal fibroblasts was an independent poor prognostic factor in
      both overall survival and disease-free survival. CD10 could be a promising target
      for the treatment of ESCC. 

PMID- 24895168
TI  - Extraperitoneal and intraperitoneal behavior of several biological meshes
      currently used to repair abdominal wall defects.
AB  - BACKGROUND: This study compares the behavior of several cross- and noncrosslinked
      biomeshes (Permacol(r), CollaMend(r), Surgisis(r), Tutomesh(r), and Strattice(r))
      currently used for abdominal wall repair when implanted intraperitoneally and
      extraperitoneally. Material and Methods. Intraperitoneal (IP) implants were fixed
      on the parietal peritoneum and partial abdominal wall defects (EP) were repaired
      using each of the biomeshes, in the rabbit abdominal wall. After 90 days of
      implant, the biomeshes were examined to assess biomesh degradation, collagen I
      and III expression (Sirius red staining) and the host macrophage response
      (immunohistochemistry). Results. Following implant, the thinner noncrosslinked
      biomeshes Tutomesh and Surgisis, were almost fully degraded in both models. In
      contrast, Strattice behavior was similar to crosslinked biomeshes, showing
      negligible degree of degradation. This mesh also showed high expression of
      collagen I, similar to the crosslinked. The noncrosslinked materials elicited
      lower macrophage counts, significantly so for Strattice. In IP and EP models,
      Permacol showed similarly high macrophages while counts were lower for CollaMend
      and Surgisis in the EP model. Conclusions. The intra or extraperitoneal implant
      of the different meshes did not affect host tissue incorporation or mesh
      degradation. The crosslinked biomeshes induced a more intense macrophage response
      regardless of their IP or EP location.

PMID- 24895169
TI  - Gene of the month. AMP kinase (PRKAA1).
AB  - The PRKAA1 gene encodes the catalytic alpha-subunit of 5' AMP-activated protein
      kinase (AMPK). AMPK is a cellular energy sensor that maintains energy homeostasis
      within the cell and is activated when the AMP/ATP ratio increases. When
      activated, AMPK increases catabolic processes that increase ATP synthesis and
      inhibit anabolic processes that require ATP. Additionally, AMPK also plays a role
      in activating autophagy and inhibiting energy consuming processes, such as
      cellular growth and proliferation. Due to its role in energy metabolism, it could
      act as a potential target of many therapeutic drugs that could be useful in the
      treatment of several diseases, for example, diabetes. Moreover, AMPK has been
      shown to be involved in inhibiting tumour growth and metastasis, and has also
      been implicated in the pathology of neurodegenerative and cardiac disorders.
      Hence, a better understanding of AMPK and its role in various pathological
      conditions could enable the development of strategies to use it as a therapeutic
      target.

PMID- 24895170
TI  - Programmable design of functional ribonucleoprotein complexes.
AB  - Ribonucleoprotein (RNP) complexes are widespread in nature and play crucial roles
      in gene regulation, RNA processing, and translation. Novel technologies, such as
      CRISPR-mediated genome engineering, stress the potential of RNP complexes to
      carry out complex tasks in molecular biology. Here we report a bottom-up approach
      for the programmable self-assembly of RNP complexes. The building blocks for RNP
      complex formation are RNAs and Pumilio proteins that can bind to RNA sequence
      specifically. Correct RNP assembly triggers protein complementation of a
      tripartite GFP, thereby resulting in up to 25-fold increased fluorescence, and is
      strictly dependent on the correct RNA sequences. Our results indicate that
      Pumilio and guide RNAs are suitable building blocks for the correct self-assembly
      of RNP complexes consisting of up to six different components. Self-assembling
      RNP complexes might prove useful for complex biotechnological applications in RNA
      sensing, imaging, or processing. 

PMID- 24895171
TI  - Facile synthesis of chiral spirooxindole-based isotetronic acids and 5-1H-pyrrol
      2-ones through cascade reactions with bifunctional organocatalysts.
AB  - Unprecedented organocatalyzed asymmetric cascade reactions have been developed
      for the facile synthesis of chiral spirooxindole-based isotetronic acids and 5-1H
      pyrrol-2-ones.The asymmetric 1,2-addition reactions of alpha-ketoesters to
      isatins and imines by using an acid-base bifunctional 6'-OH cinchona alkaloid
      catalyst, followed by cyclization and enolization of the resulting adducts, gave
      chiral spiroisotetronic acids and 5-1H-pyrrol-2-ones, respectively, in excellent
      optical purities (up to 98 % ee). FT-IR analysis supported the existence of
      hydrogen-bonding interaction between the 6'-OH group of the cinchona catalyst and
      an isatin carbonyl group, an interaction that might be crucial for catalyst
      activity and stereocontrol. 

PMID- 24895173
TI  - Fluorescence microscopy with 6 nm resolution on DNA origami.
AB  - Resolution of emerging superresolution microscopy is commonly characterized by
      the width of a point-spread-function or by the localization accuracy of single
      molecules. In contrast, resolution is defined as the ability to separate two
      objects. Recently, DNA origamis have been proven as valuable scaffold for self
      assembled nanorulers in superresolution microscopy. Here, we use DNA origami
      nanorulers to overcome the discrepancy of localizing single objects and
      separating two objects by resolving two docking sites at distances of 18, 12, and
      6 nm by using the superresolution technique DNA PAINT(point accumulation for
      imaging in nanoscale topography). For the smallest distances, we reveal the
      influence of localization noise on the yield of resolvable structures that we
      rationalize by Monte Carlo simulations. 

PMID- 24895174
TI  - Globuli ossei in the long limb bones of Pleurodeles waltl (Amphibia, Urodela,
      Salamandridae).
AB  - To date, little is known about the structure of the cells and the fibrillar
      matrix of the globuli ossei, globular structures showing histochemical properties
      of an osseous tissue, sometimes found in the resorption front of the
      hypertrophied cartilage in many tetrapods, and easily observed in the long bones
      of the Urodele Pleurodeles waltl. Here, we present the results obtained from the
      appendicular long bones of metamorphosed juveniles and subadults using
      histological and histochemical methods and transmission electron microscopy. The
      distal part of the cone-shaped cartilage contains a heterogeneous cell population
      composed of the typical "light" hypertrophic chondrocytes and scarce "dark"
      hypertrophic chondrocytes. The "dark" chondrocytes display ultrastructural
      characteristics suggesting that they probably undergo degeneration through
      chondroptosis. However, in the hypertrophic, calcified cartilage close to the
      erosion front by the marrow, several noninvaded chondrocytic lacunae retained
      cells that do not show any morphological characteristics of degeneration and that
      cannot be identified as regular chondrocytes or osteocytes. These modified
      chondrocytes that have lost their regular morphology, appear to be active in the
      terminal cartilage and synthesize collagen fibrils of a peculiar diameter
      intermediate between the Type I collagen found in bone and the Type II collagen
      characteristic of cartilage. It is suggested that the local occurrence of globuli
      ossei is linked to a low rate of longitudinal growth as is the case in the long
      bones of postmetamorphic urodeles.

PMID- 24895175
TI  - Asymmetric hearing loss and tinnitus.

PMID- 24895172
TI  - Deorphaning pyrrolopyrazines as potent multi-target antimalarial agents.
AB  - The discovery of pyrrolopyrazines as potent antimalarial agents is presented,
      with the most effective compounds exhibiting EC50 values in the low nanomolar
      range against asexual blood stages of Plasmodium falciparum in human red blood
      cells, and Plasmodium berghei liver schizonts, with negligible HepG2
      cytotoxicity. Their potential mode of action is uncovered by predicting
      macromolecular targets through avant-garde computer modeling. The consensus
      prediction method suggested a functional resemblance between ligand binding sites
      in non-homologous target proteins, linking the observed parasite elimination to
      IspD, an enzyme from the non-mevalonate pathway of isoprenoid biosynthesis, and
      multi-kinase inhibition. Further computational analysis suggested essential P.
      falciparum kinases as likely targets of our lead compound. The results obtained
      validate our methodology for ligand- and structure-based target prediction,
      expand the bioinformatics toolbox for proteome mining, and provide unique access
      to deciphering polypharmacological effects of bioactive chemical agents. 

PMID- 24895176
TI  - Medicinal plants and their natural components as future drugs for the treatment
      of burn wounds: an integrative review.
AB  - Burn wound healing is a complicated process including inflammation, re
      epithelialization, granulation, neovascularization and wound contraction. Several
      biochemicals are involved in burn healing process including antioxidants,
      cytokines and liver and kidney damage biomarkers. Although several preparations
      are available for the management of burn wound, there is still a necessity of
      researching for efficacious medicine. The aim of the present study was to
      evaluate herbal preparations and their phytochemical constituents for burn wound
      management. For this purpose, electronic databases including Pubmed, Scirus,
      Scopus and Cochrane library were searched from 1966 to July 2013 for in vitro, in
      vivo or clinical studies which examined the effect of any herbal preparation on
      different types of burn wound. Only 3 human studies were found to include in this
      review. In contrast, there were 62 in vivo and in vitro studies that show the
      need for more clinical trials to prove the plant's potential to cure burn wound.
      Among single herbal preparations, Allium sativum, Aloe vera, Centella asiatica
      and Hippophae rhamnoides showed the best burn wound healing activity. Flavonoids,
      alkaloids, saponins and phenolic compounds were active constituents present in
      different herbs facilitating wound closure. Glycosides including madecassoside
      and asiaticoside and proteolytic enzymes were among the main active components.
      Phytochemicals represented positive activity at different stages of burn wound
      healing process by various mechanisms including antimicrobial, anti-inflammatory,
      antioxidant, collagen synthesis stimulation, cell proliferative and angiogenic
      effect. Overall, several herbal medicaments have shown marked activity in the
      management of wounds-especially burn wounds-and therefore can be considered as an
      alternative source of treatment. Furthermore, various natural compounds with
      verified burn-induced wound healing potential can be assumed as future natural
      drugs. 

PMID- 24895178
TI  - Safety signal detection: the relevance of literature review.
AB  - Adverse drug reactions (ADRs) represent an important risk for patients and have a
      significant economic impact on health systems. ADRs are the fifth most common
      cause of hospital death, with a burden estimated at 197,000 deaths per year in
      the EU. This has a societal cost of <euro>79 billion per year. Because of this
      strong impact in public health, regulatory authorities (RAs) worldwide are
      implementing new pharmacovigilance legislation to promote and protect public
      health by reducing the burden of ADRs through the detection of safety signals.
      Although, traditionally, signal detection activities have mainly been performed
      based on spontaneous reporting from healthcare professionals and national health
      RAs, the new pharmacovigilance legislation underlines the relevance of other
      sources of information (such as scientific literature) for the evaluation of the
      benefit-risk balance of a certain product. This review aims to highlight the
      relevance of periodic scientific literature screening in the safety signal
      detection process. The authors present four practical examples where a safety
      signal that was detected from a literature report had an impact on the lifecycle
      of a drug. In addition, based on practical experience of the screening of medical
      and scientific literature for safety purposes, this article analyses the
      requirements of the new pharmacovigilance guidelines on literature screening and
      highlights the need for the implementation of a literature review procedure and
      the main challenges encountered when performing literature screening for safety
      aspects. 

PMID- 24895177
TI  - Development of an adherence-enhancing intervention in topical treatment termed
      the topical treatment optimization program (TTOP).
AB  - Psoriasis is a common, disabling, chronic, relapsing, inflammatory disorder of
      the skin with a worldwide prevalence of 2-3 % in which adherence to treatment is
      often poor. The majority of individuals have limited disease that is being
      treated with topical medication according to existing guidelines. Adherence rates
      are lower for topical compared with systemic treatment. Low medication adherence
      is a major problem for patients with chronic disorders as it results in
      suboptimal treatment outcomes, increased risk for development of concomitant
      diseases, inefficient use of health resources and considerable losses to society.
      However, to date no adherence-enhancing intervention has been developed for
      psoriasis patients under topical treatment. In this article, we report the
      development of the topical treatment optimization program (TTOP). The TTOP
      intervention aims to improve the information given to the patients and to result
      in an engaged patient-physician relationship. Application of the TTOP
      intervention in daily clinical practice may lead to a significant increase of
      adherence and the successful management of psoriasis and other chronic skin
      disorders. 

PMID- 24895166
TI  - The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment.
AB  - Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in
      the human circulation. Traditionally, neutrophils are viewed as the first line of
      defense against infections and as a major component of the inflammatory process.
      In addition, accumulating evidence suggest that neutrophils may also play a key
      role in multiple aspects of cancer biology. The possible involvement of
      neutrophils in cancer prevention and promotion was already suggested more than
      half a century ago, however, despite being the major component of the immune
      system, their contribution has often been overshadowed by other immune components
      such as lymphocytes and macrophages. Neutrophils seem to have conflicting
      functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2)
      sub-populations. The aim of this review is to discuss the varying nature of
      neutrophil function in the cancer microenvironment with a specific emphasis on
      the mechanisms that regulate neutrophil mobilization, recruitment and activation.

PMID- 24895179
TI  - The clinical impact of different coagulometers on patient outcomes.
AB  - INTRODUCTION: Long-term anticoagulation therapy using vitamin K antagonists (VKA)
      is used in millions of patients worldwide to reduce the risk of thrombotic or
      thromboembolic events. Control and monitoring of VKA therapy is improved by the
      regular self-measurement of international normalized ratio (INR) using a home
      monitoring device. This retrospective analysis of a large cohort of patients in
      the Netherlands seeks to determine whether the choice of INR monitor could have a
      clinical impact on patient outcomes. METHODS: The National Thrombosis Service
      provides medical supervision, training and support to anticoagulant patients
      eligible for home-monitoring of INR in the Netherlands. Two INR monitors
      (CoaguChek XS and INRatio2) have been distributed at random to patients since
      June 2011, and patient self-testing data (INR measurements and other clinical
      parameters) have been recorded to measure and improve treatment outcomes. The
      data have been retrospectively analyzed to determine any effect of the choice of
      monitor. Univariate and multivariate statistical tests are used to assess any
      differences between groups in terms of efficacy and safety parameters. RESULTS:
      Data from 4,326 patients were collated, and 156,507 INR values were included in
      the analysis. Over half the patients (54.3%) were being treated for atrial
      fibrillation, and 77.6% were prescribed acenocoumarol. There were few differences
      between the patient populations using the two different monitors. Anticoagulant
      control overall was good, with high percentage of time (87.9%) in the appropriate
      INR range and low incidence of excessively high or low INR values (0.085/month).
      Minor clinical events related to safety were low (0.78 per patient-year) and
      showed few differences between monitors. Mortality rates were similar [hazard
      ratio (HR) 1.05, 95% confidence interval (CI) 0.65-1.70]. CONCLUSION: Self
      testing data from a large cohort of patients in the Netherlands suggest that
      there is no clinically relevant effect of the choice of coagulation monitor
      (CoaguChek XS or INRatio2) on the time in therapeutic range (TTR), minor or fatal
      outcomes of long-term anticoagulation management.

PMID- 24895180
TI  - Review: Occult hepatitis C virus infection: still remains a controversy.
AB  - Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV
      RNA in the liver cells or peripheral blood mononuclear cells of the patients
      whose serum samples test negative for HCV RNA, with or without presence of HCV
      antibodies. The present study reviews the existing literature on the persistence
      of occult hepatitis C virus infection, with description of the clinical
      characteristics and methods for identification of occult hepatitis C. Occult
      hepatitis C virus infection was detected in patients with abnormal results of
      liver function tests of unknown origin, with HCV antibodies and HCV RNA
      negativity in serum, and also in patients with spontaneous or treatment-induced
      recovery from hepatitis C. The viral replication in the liver cells and/or
      peripheral blood mononuclear cells was present in all clinical presentations of
      occult hepatitis C. The peripheral blood mononuclear cells represent an extra
      hepatic site of HCV replication. The reason why HCV RNA was not detectable in the
      serum of patients with occult hepatitis C, could be the low number of circulating
      viral particles not detectable by the diagnostic tests with low sensitivity. It
      is uncertain whether occult hepatitis C is a different clinical entity or just a
      form of chronic hepatitis C virus infection. Data accumulated over the last
      decade demonstrated that an effective approach to the diagnosis of HCV infection
      would be the implementation of more sensitive HCV RNA diagnostic assays, and
      also, examination of the presence of viral particles in the cells of the immune
      system.

PMID- 24895181
TI  - The testis of greater white-toothed shrew Crocidura russula in Southern European
      populations: a case of adaptive lack of seasonal involution?
AB  - Males of all seasonal breeding mammals undergo circannual periods of testis
      involution resulting in almost complete ablation of the germinative epithelium.
      We performed a morphometric, histological, hormonal, and gene-expression study of
      the testes from winter and summer males of the greater white-toothed shrew,
      Crocidura russula, in populations of the southeastern Iberian Peninsula.
      Unexpectedly, we found no significant differences between the two study groups.
      Surprisingly, female data confirmed a non-breeding period in the summer,
      evidencing that males retain full testis function even when most females are not
      receptive. This situation, which has not been described before, does not occur in
      northern populations of the same species where, in addition, the reproductive
      cycle is inverted with respect to those in the south, as the non-breeding period
      occurs in winter instead in summer. Considering that the non-reproductive period
      shortens at lower latitude locations, we hypothesize that in southern populations
      the non-breeding period is short enough to make testis regression inefficient in
      terms of energy savings, because: (1) testes of C. russula are very small, a
      condition derived from their monogamy that implies low investment in
      spermatogenesis; and (2) the spermatogenic cycle of this species is slow and
      long. The inverted seasonal breeding cycle and the lack of seasonal testis
      regression described here are new adaptive processes that deserve further
      research, and provide evidence that the genetic and hormonal mechanisms
      controlling reproduction timing in mammals are more plastic and versatile than
      initially suspected.

PMID- 24895183
TI  - Design of a combinational magnesium catalyst for the stereocontrolled cross
      reaction of enones.
AB  - The first stereocontrolled cross reaction of enones has been realized. A novel
      combinational magnesium catalyst was designed to address the enantioselectivity
      problem between reaction partners with an intermolecular symmetric structure and
      bearing identical functional groups. This new catalytic strategy was proven to be
      effective to introduce high levels of enantioselectivity in the cross reaction of
      enones. 

PMID- 24895182
TI  - Structural design of disialoganglioside GD2 and CD3-bispecific antibodies to
      redirect T cells for tumor therapy.
AB  - Antibody-based immunotherapy has proven efficacy for patients with high-risk
      neuroblastoma. However, despite being the most efficient tumoricidal effectors, T
      cells are underutilized because they lack Fc receptors. Using a monovalent single
      chain fragment (ScFv) platform, we engineered tandem scFv bispecific antibodies
      (BsAbs) that specifically target disialoganglioside (GD2) on tumor cells and CD3
      on T cells. Structural variants of BsAbs were constructed and ranked based on
      binding to GD2, and on competency in inducing T-cell-mediated tumor cytotoxicity.
      In vitro thermal stability and binding measurements were used to characterize
      each of the constructs, and in silico molecular modeling was used to show how the
      orientation of the variable region heavy (VH) and light (VL) chains of the anti
      GD2 ScFv could alter the conformations of key residues responsible for high
      affinity binding. We showed that the VH-VL orientation, the (GGGGS)3 linker,
      disulfide bond stabilization of scFv, when combined with an affinity matured
      mutation provided the most efficient BsAb to direct T cells to lyse GD2-positive
      tumor cells. In vivo, the optimized BsAb could efficiently inhibit melanoma and
      neuroblastoma xenograft growth. These findings provide preclinical validation of
      a structure-based method to assist in designing BsAb for T-cell-mediated therapy.

PMID- 24895185
TI  - Ultrastructure of spermatozoa of Orsolobidae (Haplogynae, Araneae) with
      implications on the evolution of sperm transfer forms in Dysderoidea.
AB  - Haplogynae are highly diverse with respect to the primary male genital system and
      sperm characteristics. Additionally, all sperm transfer forms (STF) known for
      spiders are present. Besides individually transferred sperm (cleistospermia),
      sperm are transferred as conjugates, both primary (synspermia) and secondary
      sperm conjugates (coenospermia, rouleaux) occur. Nevertheless, the ultrastructure
      of spermatozoa and STF are described for few Haplogynae and often only one
      representative species was studied, resulting in a superficial insight in the
      evolution of these traits. To elucidate the evolution of STF within Haplogynae we
      investigated representatives of four genera of the dysderoid family Orsolobidae.
      Our data show the presence of synspermia (Orsolobus, Osornolobus, Hickmanolobus,
      and Tasmanoonops) and also cleistospermia (Osornolobus). The occurrence of
      different STF within one family or even genus has not been described for any
      other spider taxon so far. Moreover, the synspermia of species of Tasmanoonops
      and Hickmanolobus were not covered by a secretion sheath suggesting a previously
      unknown strategy of transferring sperm that is possibly related to sperm
      residency time or female triggered processes after copulation. Based on serial
      ultrathin sectioning and subsequent 3D-reconstruction, we obtained detailed
      measurements revealing remarkable size differences of STF. To evaluate the
      previously suggested correlation with the most distal region of the spermophor
      inside the embolus (intromittent part of the copulatory organ) we measured the
      diameter of the spermophor using micro-computed X-ray tomography data to obtain
      corresponding morphometric parameters. Based on these data only two species show
      similarity in STF and spermophor diameter.

PMID- 24895186
TI  - Effect of the bulkiness of the end functional amide groups on the optical,
      gelation, and morphological properties of oligo(p-phenylenevinylene) pi-gelators.
AB  - Herein, we describe the role of end functional groups in the self-assembly of
      amide-functionalized oligo(p-phenylenevinylene) (OPV) gelators with different end
      groups. The interplay between hydrogen-bonding and pi-stacking interactions was
      controlled by the bulkiness of the end functional groups, thereby resulting in
      aggregates of different types, which led to the gelation of a wide range of
      solvents. The variable-temperature UV/Vis absorption and fluorescence
      spectroscopic features of gelators with small end-groups revealed the formation
      of 1D H-type aggregates in CHCl(3). However, under fast cooling in toluene, 1D H
      type aggregates were formed, whereas slow cooling resulted in 2D H-type
      aggregates. OPV amide with bulky dendritic end-group formed hydrogen-bonded
      random aggregates in toluene and a morphology transition from vesicles into
      fibrous aggregates was observed in THF. Interestingly, the presence of bulky end
      group enhanced fluorescence in the xerogel state and aggregation in polar
      solvents. The difference between the aggregation properties of OPV amides with
      small and bulky end-groups allowed the preparation of self-assembled structures
      with distinct morphological and optical features.

PMID- 24895187
TI  - alpha- and beta-Lipomycin: total syntheses by sequential stille couplings and
      assignment of the absolute configuration of all stereogenic centers.
AB  - 40 years ago spectroscopy, derivatization, and degradation revealed the
      structures of alpha-lipomycin and its aglycon beta-lipomycin except for the
      configurations of their side-chain stereocenters. We synthesized all relevant
      beta-lipomycin candidates: the (12R,13S) isomer has the same specific rotational
      value as the natural product. By the same criterion the (12R,13S)-configured D
      digitoxide is identical to alpha-lipomycin. We double-checked our assignments by
      degrading alpha- and beta-lipomycin to the diesters 33 and 34 and proving their
      3D structures synthetically. 

PMID- 24895184
TI  - Developmental trajectories of Body Mass Index from infancy to 18 years of age:
      prenatal determinants and health consequences.
AB  - BACKGROUND: Knowledge on the long-term development of adiposity throughout
      childhood/adolescence and its prenatal determinants and health sequelae is
      lacking. We sought to (1) identify trajectories of Body Mass Index (BMI) from 1
      to 18 years of age, (2) examine associations of maternal gestational smoking and
      early pregnancy overweight with offspring BMI trajectories and (3) determine
      whether BMI trajectories predict health outcomes: asthma, lung function
      parameters (forced expiratory volume in one second (FEV1)/forced vital capacity
      (FVC) ratio), and blood pressure, at 18 years. METHODS: The Isle of Wight birth
      cohort, a population-based sample of 1456 infants born between January 1989 and
      February 1990, was prospectively assessed at ages 1, 2, 4, 10 and 18 years. Group
      based trajectory modelling was applied to test for the presence of latent BMI
      trajectories. Associations were assessed using log-binomial and linear regression
      models. RESULTS: Four trajectories of BMI were identified: 'normal', 'early
      persistent obesity', 'delayed overweight', and 'early transient overweight'. Risk
      factors for being in the early persistent obesity trajectory included maternal
      smoking during pregnancy (RR 2.16, 95% CI 1.02 to 4.68) and early pregnancy
      overweight (3.16, 1.52 to 6.58). When comparing the early persistent obesity to
      the normal trajectory, a 2.15-fold (1.33 to 3.49) increased risk of asthma, 3.2%
      (0.4% to 6.0%) deficit in FEV1/FVC ratio, and elevated systolic 11.3 mm Hg (7.1
      to 15.4) and diastolic 12.0 mm Hg (8.9 to 15.1) blood pressure were observed at
      age 18 years. CONCLUSIONS: Maternal prenatal exposures show prolonged effects on
      offspring's propensity towards overweight-obesity. Distinct morbid BMI
      trajectories are evident during the first 18 years of life that are associated
      with higher risk of asthma, reduced FEV1/FVC ratio, and elevated blood pressure.

PMID- 24895192
TI  - Efficacy and safety of labour induction in patients with a single previous
      caesarean section: a proposal for a clinical protocol.
AB  - PURPOSE: To evaluate the efficacy and safety of induction in women with a single
      prior Caesarean section. METHODS: This was a cohort study in which we included
      all singleton pregnancies in patients with a single prior Caesarean who delivered
      between 2007 and 2012. Methods of induction were ocytocic infusion plus amniotomy
      (if Bishop score >=6) or insertion of a Foley catheter (Bishop <6). RESULTS: Of
      the 2,075 patients included, 806 (38.8 %) had an elective repeat Caesarean, 1,045
      (50.4 %) went into spontaneous labour, 89 (4.3 %) were induced by artificial
      rupture of the membranes and infusion of ocytocics and 135 (6.5 %) were induced
      using a Foley catheter. Rates of vaginal delivery were 79.2, 79.8 and 43.7 %,
      respectively. Six cases of uterine rupture were reported in the group of patients
      who went into spontaneous labour. There was no difference between groups with
      regard to neonatal morbidity. On multivariate analysis, risk factors for
      Caesarean delivery were macrosomia (OR 2.04, 95 % CI 1.31-3.18) and induction by
      Foley catheter (OR 3.73, 95 % CI 2.47-5.62); protective factors were previous
      vaginal delivery (OR 0.41, 95 % CI 0.29-0.57) and cervical dilatation (OR 0.84,
      95 % CI 0.78-0.91). CONCLUSIONS: Uterine induction after a single Caesarean
      section with ocytocic infusion and amniotomy where the cervix is favourable does
      not appear to entail any significant added risk in terms of maternal or foetal
      morbidity. Foley catheter induction is a reasonable option if the cervix is not
      ripe.

PMID- 24895193
TI  - Limits and complications of laparoscopic myomectomy: which are the best
      predictors? A large cohort single-center experience.
AB  - PURPOSE: To determine whether a correlation exists between size, location, type
      of myomas and perioperative outcomes. METHODS: This is a observational study in
      women undergone to laparoscopic myomectomy (LM) because of single symptomatic
      myoma >4 cm in diameter. We collected data about general features, surgical
      outcomes, intraoperative/postoperative complications and time to return to normal
      activity. RESULTS: A total of 444 patients (mean age 36.7 +/- 6.4 years) resulted
      eligible for the study. Myomas sized between 8 and 12 cm were linked to an
      increased amount of blood loss (significantly higher in intramural than
      subserosal myoma). The removal of intramural myomas >8 cm and the subserosal ones
      >12 cm required a significant longer surgical time. Patients returned 17.9 +/-
      9.5 days after surgery to their personal activities. Six cases (1.35 %) required
      conversion to laparotomy, and only in two cases blood transfusion was necessary.
      CONCLUSION: Myomas size and type represent the best predictors of surgical
      difficulties and possible intrapostoperative complications. Intramural myomas >8
      cm and subserosal ones >12 cm should be considered as a challenging procedure. LM
      remains the gold standard approach because of very low perioperative complication
      rate and faster return to normal activity.

PMID- 24895194
TI  - A change of heart.

PMID- 24895191
TI  - Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from
      Escherichia coli reveal the catalytic and chain-length determining mechanisms.
AB  - Octaprenyl pyrophosphate synthase (OPPs) catalyzes consecutive condensation
      reactions of one allylic substrate farnesyl pyrophosphate (FPP) and five
      homoallylic substrate isopentenyl pyrophosphate (IPP) molecules to form a C40
      long-chain product OPP, which serves as a side chain of ubiquinone and
      menaquinone. OPPs belongs to the trans-prenyltransferase class of proteins. The
      structures of OPPs from Escherichia coli were solved in the apo-form as well as
      in complexes with IPP and a FPP thio-analog, FsPP, at resolutions of 2.2-2.6 A,
      and revealed the detailed interactions between the ligands and enzyme. At the
      bottom of the active-site tunnel, M123 and M135 act in concert to form a wall
      which determines the final chain length. These results represent the first ligand
      bound crystal structures of a long-chain trans-prenyltransferase and provide new
      information on the mechanisms of catalysis and product chain elongation.

PMID- 24895195
TI  - Enhancing fatty acid ethyl ester production in Saccharomyces cerevisiae through
      metabolic engineering and medium optimization.
AB  - Biodiesels in the form of fatty acyl ethyl esters (FAEEs) are a promising next
      generation biofuel due to their chemical properties and compatibility with
      existing infrastructure. It has recently been shown that expression of a
      bacterial acyl-transferase in the established industrial workhorse Saccharomyces
      cerevisiae can lead to production of FAEEs by condensation of fatty acyl-CoAs and
      ethanol. In contrast to recent strategies to produce FAEEs in S. cerevisiae
      through manipulation of de novo fatty acid biosynthesis or a series of arduous
      genetic manipulations, we introduced a novel genetic background, which is
      comparable in titer to previous reports with a fraction of the genetic disruption
      by aiming at increasing the fatty acyl-CoA pools. In addition, we combined
      metabolic engineering with modification of culture conditions to produce a
      maximum titer of over 25 mg/L FAEEs, a 40% improvement over previous reports and
      a 17-fold improvement over our initial characterizations. Biotechnol. Bioeng.
      2014;111: 2200-2208. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24895199
TI  - From 2004 to 2014: a fruitful decade for graphene research in China.

PMID- 24895203
TI  - Targeting CDK9 by wogonin and related natural flavones potentiates the anti
      cancer efficacy of the Bcl-2 family inhibitor ABT-263.
AB  - Tumor initiation, progression and resistance to therapies are tightly associated
      with over-expression of anti-apoptotic proteins Bcl-2, Bcl-x(L), Bcl-w and Mcl-1.
      ABT-263 (Navitoclax), an orally bio-available small-molecule mimetic of the Bcl-2
      homology domain 3, inhibits Bcl-2, Bcl-x(L), and Bcl-w and has shown anti-cancer
      effects mainly on lymphomas and lymphocytic leukemia. Despite promising results
      obtained from the clinical trials, the use of ABT-263 in patients is dose-limited
      due to causing thrombocytopenia via inhibition of Bcl-x(L) in platelets. ABT-199
      specifically inhibits Bcl-2; however, its use is limited to tumors over
      expressing only Bcl-2. Besides, many tumors resist treatment due to high levels
      of Mcl-1 expression or develop resistance via up-regulation of Mcl-1 during long
      term exposure. These obstacles highlight the demand to improve the ABT-263-based
      therapy. In this study, we show that anti-cancer flavones, e.g., wogonin,
      baicalein, apigenin, chrysin and luteolin enhance ABT-263-induced apoptosis in
      different cancer cell lines and in primary AML and ALL cells by down-regulation
      of Mcl-1 expression. Importantly, wogonin does not enhance the toxicity of ABT
      263 to proliferating normal T cells and thrombocytes. Wogonin also potentiates
      the lethality of ABT-263 in cancer cells which have acquired resistance to ABT
      263. Furthermore, we show that combination of wogonin with ABT-263 promotes in
      vivo tumor regression in a human T-cell leukemia xenograft mouse model. Our study
      demonstrates that wogonin (and related flavones) reduce the effective dose of ABT
      263 thereby possibly decreasing the risk of adverse side effects.

PMID- 24895205
TI  - Highlight: a matter of taste-whales have abandoned their ability to taste food.

PMID- 24895204
TI  - Financial benefits of integration: a case of wishful thinking?

PMID- 24895202
TI  - Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.
AB  - MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in
      the hepatocyte is not fully understood. To evaluate whether circulating levels of
      miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we
      compared serum level in patients with chronic hepatitis C to other forms of liver
      injury including patients with acute liver failure and healthy controls. MiR-122
      was quantitated using sera from 35 acute liver failure patients (20 acetaminophen
      induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In
      parallel, human genomic DNA (hgDNA) levels were measured to reflect
      quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co
      infected patients, who achieved viral clearance after undergoing therapy with
      interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured
      before and throughout treatment. Serum miR-122 levels were elevated approximately
      100-fold in both acute liver failure and chronic-HCV sera as compared to controls
      (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure
      patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup
      analysis showed that chronic-HCV sera with normal aminotransferase levels showed
      elevated miR-122 despite low levels of hepatocyte necrosis. All successfully
      treated HCV patients showed a significant Log10 decrease in miR-122 levels
      ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients
      have very elevated serum miR-122 levels in the range of most patients with severe
      hepatic injury leading to acute liver failure. Eradication of HCV was associated
      with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic
      injury may be active in chronic-HCV to explain the exaggerated circulating levels
      of miR-122 observed.

PMID- 24895206
TI  - Sulforaphane suppresses LPS-induced or TPA-induced downregulation of PDCD4 in RAW
      264.7 cells.
AB  - Sulforaphane is a natural chemopreventive isothiocyanate and abundantly found in
      various cruciferous vegetables. Although chemopreventive activity of sulforaphane
      is well documented, the detailed biochemical mechanism(s), underlying how it
      regulates the protein translation process to antagonize pro-inflammatory
      responses are largely unclear. In the present study, we show that
      lipopolysaccharide (LPS) or 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment
      reduces cellular levels of PDCD4, and this event is mediated by affecting both
      transcription and proteolysis in RAW 264.7 cells. We show that LPS-mediated or
      TPA-mediated PDCD4 downregulation is catalyzed by the activation of intracellular
      Akt1 or S6K1 kinases and that sulforaphane suppresses LPS-induced or TPA-induced
      Akt1 or S6K1 activation, thereby resulting in the attenuation of PDCD4
      downregulation in RAW 264.7 cells. We propose that sulforaphane suppression of
      PDCD4 downregulation serves as a novel molecular mechanism to control
      proliferation in response to pro-inflammatory signals.

PMID- 24895207
TI  - The microwave-assisted ionic-liquid method: a promising methodology in
      nanomaterials.
AB  - In recent years, the microwave-assisted ionic-liquid method has been accepted as
      a promising methodology for the preparation of nanomaterials and cellulose-based
      nanocomposites. Applications of this method in the preparation of cellulose-based
      nanocomposites comply with the major principles of green chemistry, that is, they
      use an environmentally friendly method in environmentally preferable solvents to
      make use of renewable materials. This minireview focuses on the recent
      development of the synthesis of nanomaterials and cellulose-based nanocomposites
      by means of the microwave-assisted ionic-liquid method. We first discuss the
      preparation of nanomaterials including noble metals, metal oxides, complex metal
      oxides, metal sulfides, and other nanomaterials by means of this method. Then we
      provide an overview of the synthesis of cellulose-based nanocomposites by using
      this method. The emphasis is on the synthesis, microstructure, and properties of
      nanostructured materials obtained through this methodology. Our recent research
      on nanomaterials and cellulose-based nanocomposites by this rapid method is
      summarized. In addition, the formation mechanisms involved in the microwave
      assisted ionic-liquid synthesis of nanostructured materials are discussed
      briefly. Finally, the future perspectives of this methodology in the synthesis of
      nanostructured materials are proposed. 

PMID- 24895208
TI  - A fatal case of JC virus meningitis presenting with hydrocephalus in a human
      immunodeficiency virus-seronegative patient.
AB  - JC virus (JCV) is the etiologic agent of progressive multifocal
      leukoencephalopathy, JCV granule cell neuronopathy, and JCV encephalopathy.
      Whether JCV can also cause meningitis has not yet been demonstrated. We report a
      case of aseptic meningitis resulting in symptomatic hydrocephalus in a human
      immunodeficiency virus-seronegative patient. Brain imaging showed enlargement of
      ventricles but no parenchymal lesion. She had a very high JC viral load in the
      cerebrospinal fluid (CSF) and developed progressive cognitive dysfunction despite
      ventricular drainage. She was diagnosed with pancytopenia and passed away after
      5.5 months. Postmortem examination revealed productive JCV infection of
      leptomeningeal and choroid plexus cells, and limited parenchymal involvement.
      Sequencing of JCV CSF strain showed an archetype-like regulatory region. Further
      studies of the role of JCV in aseptic meningitis and in idiopathic hydrocephalus
      are warranted.

PMID- 24895209
TI  - Cytoprotective silica coating of individual mammalian cells through bioinspired
      silicification.
AB  - The cytoprotective coating of physicochemically labile mammalian cells with a
      durable material has potential applications in cell-based sensors, cell therapy,
      and regenerative medicine, as well as providing a platform for fundamental single
      cell studies in cell biology. In this work, HeLa cells in suspension were
      individually coated with silica in a cytocompatible fashion through bioinspired
      silicification. The silica coating greatly enhanced the resistance of the HeLa
      cells to enzymatic attack by trypsin and the toxic compound poly(allylamine
      hydrochloride), while suppressing cell division in a controlled fashion. This
      bioinspired cytocompatible strategy for single-cell coating was also applied to
      NIH 3T3 fibroblasts and Jurkat cells. 

PMID- 24895210
TI  - Differential susceptibility of brain regions to tributyltin chloride toxicity.
AB  - Tributyltin (TBT), a well-known endocrine disruptor, is an omnipresent
      environmental pollutant and is explicitly used in many industrial applications.
      Previously we have shown its neurotoxic potential on cerebral cortex of male
      Wistar rats. As the effect of TBT on other brain regions is not known, we planned
      this study to evaluate its effect on four brain regions (cerebellum, hippocampus,
      hypothalamus, and striatum). Four-week-old male Wistar rats were gavaged with a
      single dose of TBT-chloride (TBTC) (10, 20, and 30 mg/kg) and sacrificed on days
      3 and 7, respectively. Effect of TBTC on blood-brain barrier (BBB) permeability
      and tin (Sn) accumulation were measured. Oxidative stress indexes such as
      reactive oxygen species (ROS), reduced and oxidized glutathione (GSH/GSSG) ratio,
      lipid peroxidation, and protein carbonylation were analyzed as they play an
      imperative role in various neuropathological conditions. Since metal catalyzed
      reactions are a major source of oxidant generation, levels of essential metals
      like iron (Fe), zinc (Zn), and calcium (Ca) were estimated. We found that TBTC
      disrupted BBB and increased Sn accumulation, both of which appear significantly
      correlated. Altered metal homeostasis and ROS generation accompanied by elevated
      lipid peroxidation and protein carbonylation indicated oxidative damage which
      appeared more pronounced in the striatum than in cerebellum, hippocampus, and
      hypothalamus. This could be associated to the depleted GSH levels in striatum.
      These results suggest that striatum is more susceptible to TBTC induced oxidative
      damage as compared with other brain regions under study.

PMID- 24895211
TI  - Does menopause effect nasal mucociliary clearance time?
AB  - The aim of this study was to investigate the effect of menopause on nasal
      mucociliary clearance time by comparing the results of premenopausal and
      postmenopausal women. A total of 60 women met the criteria and were divided into
      two groups: premenopausal women (n = 30) and postmenopausal women (n = 30). Nasal
      mucociliary clearance time of these women was measured and compared. Moreover,
      the correlation between nasal mucociliary clearance time and menopause duration
      in postmenopausal women was evaluated. Statistical analysis was performed using
      the SPSS (Statistical Package for the Social Sciences) 13.0 Evaluation for
      Windows. Normal distribution of continuous variables was tested with Kolmogorov
      Smirnov test. Chi square test was used for comparisons between categorical
      variables. Kruskal-Wallis test and Mann-Whitney U tests were used for continuous
      variables when comparing the groups. The statistically significant level was
      accepted as p value <0.05. The mean nasal mucociliary clearance time in
      premenopausal and postmenopausal women was 11.43 +/- 2.81 (7-16) and 16.76 +/-
      2.73 (12-22), respectively. The mean nasal mucociliary clearance time in
      postmenopausal women was significantly longer than in premenopausal women (p <
      0.0001). Also, there was positive correlation between menopause duration and
      nasal mucociliary clearance time in postmenopausal women (r = 0.833, p < 0.0001).
      The clinicians must keep in mind that nasal mucociliary clearance time in
      postmenopausal women is prolonged and must follow up women in postmenopausal
      period more closely for respiratory tract diseases, sinonasal and middle ear
      infections.

PMID- 24895213
TI  - Specific potassium ion interactions facilitate homocysteine binding to betaine
      homocysteine S-methyltransferase.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent
      methyltransferase that uses betaine as the methyl donor for the remethylation of
      homocysteine to form methionine. This reaction supports S-adenosylmethionine
      biosynthesis, which is required for hundreds of methylation reactions in humans.
      Herein we report that BHMT is activated by potassium ions with an apparent K(M)
      for K+ of about 100 uM. The presence of potassium ions lowers the apparent K(M)
      of the enzyme for homocysteine, but it does not affect the apparent K(M) for
      betaine or the apparent k(cat) for either substrate. We employed molecular
      dynamics (MD) simulations to theoretically predict and protein crystallography to
      experimentally localize the binding site(s) for potassium ion(s). Simulations
      predicted that K+ ion would interact with residues Asp26 and/or Glu159. Our
      crystal structure of BHMT bound to homocysteine confirms these sites of
      interaction and reveals further contacts between K+ ion and BHMT residues Gly27,
      Gln72, Gln247, and Gly298. The potassium binding residues in BHMT partially
      overlap with the previously identified DGG (Asp26-Gly27-Gly28) fingerprint in the
      Pfam 02574 group of methyltransferases. Subsequent biochemical characterization
      of several site-specific BHMT mutants confirmed the results obtained by the MD
      simulations and crystallographic data. Together, the data herein indicate that
      the role of potassium ions in BHMT is structural and that potassium ion
      facilitates the specific binding of homocysteine to the active site of the
      enzyme.

PMID- 24895214
TI  - Direct biosynthesis of adipic acid from a synthetic pathway in recombinant
      Escherichia coli.
AB  - The C6 dicarboxylic acid, adipic acid, is an important platform chemical in
      industry. Biobased production of adipic acid is a promising alternative to the
      current petrochemical route. Here, we report biosynthesis of adipic acid using an
      artificial pathway inspired by the reversal of beta-oxidation of dicarboxylic
      acids. The biosynthetic pathway comprises condensation of acetyl-CoA and succinyl
      CoA to form the C6 backbone and subsequent reduction, dehydration, hydrogenation,
      and release of adipic acid from its thioester. The pathway was first tested in
      vitro with reconstituted pathway enzymes and then functionally introduced into
      Escherichia coli for the biosynthesis and excretion of adipic acid into the
      culture medium. The production titer was increased by approximately 20-fold
      through the combination of recruiting enzymes that were more suitable to catalyze
      the synthetic reactions and increasing availability of the condensation
      substrates. This work demonstrates direct biosynthesis of adipic acid via non
      natural synthetic pathway, which may enable its renewable production.

PMID- 24895212
TI  - Negative regulation of the androgen receptor gene through a primate-specific
      androgen response element present in the 5' UTR.
AB  - The androgen receptor (AR) is a widely expressed ligand-activated transcription
      factor which mediates androgen signalling by binding to androgen response
      elements (AREs) in normal tissue and prostate cancer (PCa). Within tumours, the
      amount of AR plays a crucial role in determining cell growth, resistance to
      therapy and progression to fatal castrate recurrent PCa in which prostate cells
      appear to become independent of androgenic steroids. Despite the pivotal role of
      the AR in male development and fertility and all stages of PCa development, the
      mechanisms governing AR expression remain poorly understood. In this work, we
      describe an active nonconsensus androgen response element (ARE) in the 5' UTR of
      the human AR gene. The ARE represses transcription upon binding of activated AR,
      and this downregulation is relieved by disruption of the regulatory element
      through mutation. Also, multiple species comparison of the genomic region reveals
      that this ARE is specific to primates, leading to the conclusion that care must
      be exercised when elucidating the operation of the human AR in PCa based upon
      rodent promoter studies. 

PMID- 24895215
TI  - Bio-hybrid cell-based actuators for microsystems.
AB  - As we move towards the miniaturization of devices to perform tasks at the nano
      and microscale, it has become increasingly important to develop new methods for
      actuation, sensing, and control. Over the past decade, bio-hybrid methods have
      been investigated as a promising new approach to overcome the challenges of
      scaling down robotic and other functional devices. These methods integrate
      biological cells with artificial components and therefore, can take advantage of
      the intrinsic actuation and sensing functionalities of biological cells. Here,
      the recent advancements in bio-hybrid actuation are reviewed, and the challenges
      associated with the design, fabrication, and control of bio-hybrid microsystems
      are discussed. As a case study, focus is put on the development of bacteria
      driven microswimmers, which has been investigated as a targeted drug delivery
      carrier. Finally, a future outlook for the development of these systems is
      provided. The continued integration of biological and artificial components is
      envisioned to enable the performance of tasks at a smaller and smaller scale in
      the future, leading to the parallel and distributed operation of functional
      systems at the microscale. 

PMID- 24895216
TI  - Optimization and validation of a high throughput method for detecting
      neutralizing antibodies against human papillomavirus (HPV) based on pseudovirons.
AB  - The pseudoviron-based neutralization assay is accepted as the gold standard to
      evaluate the functional humoral immune response against HPV. The goal of this
      study was to develop and optimize a human papillomavirus (HPV) neutralization
      assay using HPV pseudovirons with Gaussia luciferase (Gluc) as the reporter gene.
      For this purpose, high-titers Gluc pseudovirons were generated by cotransfecting
      293TT cells with HPV structural genes and Gluc expressing plasmids. Six types of
      neutralizing monoclonal antibodies, vaccines immunized serum samples and WHO
      international antibody standard were used to validate the new developed assay.
      The ideal circumstances of the assay were identified for cell counts (30,000/well
      for 96-well plate), pseudoviron inoculating size (100 times RLU above background)
      and incubation time (72 hr). The sensitivity of the Gluc assay was comparable to
      secreted alkaline phosphatase (SEAP) assay and higher than the green florescent
      protein (GFP) assay. The non-specific background for different types of sample
      was significantly different (rabbit sera > human sera > mouse sera, P < 0.01).
      The non-specific neutralization effects were not attributed to IgG antibody. The
      cutoff value for this assay was determined as 50% inhibition at a dilution of
      1:40. Without requirements of sample dilution and different incubation times at
      different temperature before processing, the detection time was shortened from
      more than 90 min to less than 5 min for a 96-well plate compared with the SEAP
      based assay. With the advantages of short detection time and easy-to-use
      procedure, the newly developed assay is more suitable for large sero
      epidemiological studies or clinical trials and more amenable to automation.

PMID- 24895217
TI  - Large-scale profiling of metabolic dysregulation in ovarian cancer.
AB  - Ovarian cancer is the leading cause of death in gynecologic malignancies.
      Profiling of endogenous metabolites has potential to identify changes caused by
      cancer and provide inspiring insights into cancer metabolism. To systematically
      investigate ovarian cancer metabolism, we performed metabolic profiling of 448
      plasma samples related to epithelial ovarian cancer (EOC) based on ultra
      performance liquid chromatography mass spectrometry in both positive and negative
      modes. These unbiased metabolomic profiles could well distinguish EOC from benign
      ovarian tumor (BOT) and uterine fibroid (UF). Fifty-three metabolites were
      identified as specific biomarkers for EOC, and this is the first report of
      piperine, 3-indolepropionic acid, 5-hydroxyindoleacetaldehyde and
      hydroxyphenyllactate as metabolic biomarkers of EOC. The AUC values of these
      metabolites for discriminating EOC from BOT/UF and early-stage EOC from BOT/UF
      were 0.9100/0.9428 and 0.8385/0.8624, respectively. Meanwhile, our metabolites
      were able to distinguish early-stage EOC from late-stage EOC with an AUC of
      0.8801. Importantly, analysis of dysregulated metabolic pathways extends our
      current understanding of EOC metabolism. Metabolic pathways in EOC patients are
      mainly characterized by abnormal phospholipid metabolism, altered l-tryptophan
      catabolism, aggressive fatty acid beta-oxidation and aberrant metabolism of
      piperidine derivatives. Together, these metabolic pathways provide a foundation
      to support cancer development and progression. In conclusion, our large-scale
      plasma metabolomics study yielded fundamental insights into dysregulated
      metabolism in ovarian cancer, which could facilitate clinical diagnosis, therapy,
      prognosis and shed new lights on ovarian cancer pathogenesis. 

PMID- 24895218
TI  - Chaperoning heat shock proteins: proteomic analysis and relevance for normal and
      dystrophin-deficient muscle.
AB  - Molecular chaperones play a key role in normal muscle function and during
      physiological adaptations to extensive exercise and numerous forms of cellular
      stress. The various classes of HSPs and related chaperones are also involved in
      the molecular pathogenesis of a large number of neuromuscular diseases. Several
      MS-based proteomic studies have recently shown that the expression levels of
      molecular chaperones are severely altered in dystrophin-deficient muscles.
      Dystrophin isoform Dp427 (where Dp427 is dystrophin protein of 427 kDa) is a
      large membrane cytoskeletal protein and its deficiency is the primary underlying
      cause of Duchenne muscular dystrophy. Current efforts have focused on the
      establishment of a comprehensive biomarker signature of dystrophinopathy in order
      to improve diagnostic methods, establish reliable prognostic factors and identify
      novel therapeutic targets. Following an introduction into the biology of HSPs and
      their general role in skeletal muscle, this review outlines the proteomic
      profiling of molecular chaperones in dystrophinopathy. The focus is especially on
      the molecular fate of HSPs cardiovascular HSP (HSPB7), alphaBC (HSPB5), HSP70
      (HSPA) and HSP90 (HSPC) in dystrophin-deficient muscles and their involvement in
      progressive muscular dystrophy. Furthermore, the potential usage of distinct
      chaperones as disease markers of secondary pathobiochemical changes for the
      evaluation of novel treatment options is discussed. 

PMID- 24895219
TI  - Efficient synthesis of novel 3-aryl-5-(4-chloro-2-morpholinothiazol-5-yl)-4,5
      dihydro-1H-pyrazoles and their antifungal activity alone and in combination with
      commercial antifungal agents.
AB  - The alpha,beta-unsaturated carbonyl compounds 5a-f were prepared by reaction
      between 2-chloro-4-morpholinothiazol-5-carbaldehyde 3 and substituted
      acetophenones 4a-f. Treatment of compounds 5a-f with hydrazine hydrate employing
      mild reaction conditions led to the formation of 4,5-dihydro-1H-pyrazoles 6a-f.
      Then the treatment with acetic anhydride or formic acid afforded the expected 4,5
      dihydro-1H-pyrazoles 7a-f and 8a-f. The antifungal activity of each series of
      synthesized compounds was determined against the clinically important fungi
      Candida albicans and Cryptococcus neoformans. In addition, the most active
      compounds 7e and 7f were tested in combination with the commercial antifungal
      agents: fluconazole, itraconazole, and amphotericin B. Compound 7e showed a
      synergistic effect with fluconazole against C. albicans while 7f showed
      synergistic activities with all tested antifungal drugs against the same yeast. 

PMID- 24895220
TI  - Antiangiogenic activity of xanthomicrol and calycopterin, two polymethoxylated
      hydroxyflavones in both in vitro and ex vivo models.
AB  - Our previous studies had shown xanthomicrol and calycopterin, two plant-derived
      flavonoids, to have selective antiproliferative activity against some malignant
      cell lines. The present study is focused on the investigation of antiangiogenic
      potential of these two flavonoids, using in vitro and ex vivo models.
      Xanthomicrol and calycopterin were found to have potent inhibitory effects on
      microvessel outgrowth in the rat aortic ring assay. Xanthomicrol was able to
      completely block microvessel sprouting at 10 ug/mL, and calycopterin suppressed
      microvessel outgrowth by 89% at 5 ug/mL. Suramin and thalidomide, used at 20
      ug/mL as positive controls, inhibited microvessel formation by 23% and 64%,
      respectively. The flavones also inhibited endothelial cell tube formation and
      human umbilical vein endothelial cell proliferation at 0.5, 5, and 10 ug/mL. In
      order to delineate the underlying mechanisms of antiangiogenic activity of these
      flavones, we investigated the influences of xanthomicrol and calycopterin on
      expression of vascular endothelial growth factor (VEGF) and basic-fibroblast
      growth factor (b-FGF) in endothelial cells. These flavones were able to inhibit
      VEGF expression at 0.5, 5, and 10 ug/mL, but they had little or no effect on b
      FGF expression. These findings suggest that xanthomicrol and calycopterin possess
      potent antiangiogenic activities, which may be due to their inhibitory influences
      on VEGF expression.

PMID- 24895221
TI  - The synthesis of alpha-azidoesters and geminal triazides.
AB  - Three simple methods for the synthesis of geminal triazides are described:
      Starting from 1) 3-oxocarboxylic acids, 2) iodomethyl ketones, or 3) terminal
      olefins, a range of triazidomethyl ketones can be constructed under mild
      oxidative reaction conditions by the use of IBX-SO3 K, a sulfonylated derivative
      of 2-iodoxybenzoic acid (IBX), and NaN3 as an azide source. This is the first
      report of representatives of this novel class of triazide compounds: Despite
      their high nitrogen content, the geminal triazides are easy to handle, even when
      preparative-scale syntheses are performed. (Caution: These procedures still
      require protective measures!) The triazides are now broadly available for further
      studies regarding their properties and reactivity. Furthermore, we show how the
      method can be used to provide alpha-azidoesters, which are potential building
      blocks for amino acids. 

PMID- 24895222
TI  - Rebuttal: balloon assisted tracking: a double edged sword.

PMID- 24895223
TI  - Impact of adolescent GluA1 AMPA receptor ablation in forebrain excitatory neurons
      on behavioural correlates of mood disorders.
AB  - Glutamatergic dysfunctions have recently been postulated to play a considerable
      role in mood disorders. However, molecular mechanisms underlying these effects
      have been poorly deciphered. Previous work demonstrated the contribution of GluA1
      containing AMPA receptors (AMPAR) to a depression-like and anxiety-like
      phenotype. Here we investigated the effect of temporally and spatially restricted
      gene manipulation of GluA1 on behavioural correlates of mood disorders in mice.
      Here we show that tamoxifen-induced GluA1 deletion restricted to forebrain
      glutamatergic neurons of post-adolescent mice does not induce depression- and
      anxiety-like changes. This differs from the phenotype of mice with global AMPAR
      deletion suggesting that for mood regulation AMPAR may be particularly important
      on inhibitory interneurons or already early in development. 

PMID- 24895224
TI  - Developing a framework for implementation of genetic services: learning from
      examples of testing for monogenic forms of common diseases.
AB  - Genetics in health care is shifting, and responsibilities of genetic and
      nongenetic specialists are changing, requiring new guidance on how to adapt
      health care to advances in genetic services. This paper explores facilitators and
      barriers in the process of implementation of innovations in genetic health care.
      Furthermore, lessons learnt for optimizing development of new genetic services
      are summarized. Barriers and facilitators in transition processes were identified
      using mixed methods, including an online open-ended questionnaire among
      professionals and an international expert meeting. A multi-case study approach
      was used to explore recent experiences with innovations in genetic services in
      different phases of implementation. Barriers encountered in transitions in
      genetic service provision include the following: lack of genetic knowledge and
      skills among nongenetic health care providers, resistance to new divisions of
      responsibilities, and a need for more close collaboration and communication
      between geneticists and nongeneticists. Facilitating factors include the
      following: statutory registration of genetic specialists, availability of
      essential staff and equipment, and existence of registries and guidelines. Other
      challenges are experienced in the establishment of the appropriate legal and
      financial structures. A set of points to consider for genetic innovation
      processes is proposed, addressing, e.g., transition management and cooperation
      and communication strategies. 

PMID- 24895225
TI  - Skin disease in pregnancy.

PMID- 24895226
TI  - Increased on oxidative brain injury in the diabetic rats following sepsis.
AB  - Diabetes has been the subject of recent research by increase susceptibility to
      infections, thus the aim of this study was to evaluate in animal model of
      diabetes induced by alloxan (ALX) and subjected to sepsis the parameters of
      oxidative stress on the brain. Diabetes was induced in Wistar rats by ALX (150
      mg/kg), and 15 days after, sepsis was induced by cecal ligation and puncture
      (CLP). The myeloperoxidase activity (MPO), nitrite/nitrate, oxidative damage
      parameters, and the activity of superoxide dismutase (SOD) and catalase (CAT)
      were measured in the cerebellum, hippocampus, striatum, prefrontal, and cortex in
      6, 12, and 24 h after CLP. The results showed the potentiation of diabetes with
      sepsis. We verified these potentiation on MPO levels in the cerebellum,
      hippocampus, and prefrontal and an increase of the nitrite/nitrate concentration
      in the hippocampus, striatum, prefrontal, and cortex in 24 h after sepsis
      surgery. To oxidative damage, we verified in 6 h an increase on lipid and protein
      damage parameters in the striatum and hippocampus in 24 h. When we associate
      sepsis and diabetes, the SOD and CAT activity not were altered. Thus, diabetes
      associated with sepsis exacerbates brain damage resulting from inflammation and
      oxidative stress in brain.

PMID- 24895227
TI  - A simple method for eliminating fixed-region interference of aptamer binding
      during SELEX.
AB  - Standard libraries for systematic evolution of ligands by exponential enrichment
      (SELEX) typically utilize flanking regions that facilitate amplification of
      aptamers recovered from each selection round. Here, we show that these flanking
      sequences can bias the selection process, due in part to their ability to
      interfere with the fold or function of aptamers localized within the random
      region of the library sequence. We then address this problem by investigating the
      use of complementary oligonucleotides as a means to block aptamer interference by
      each flanking region. Isothermal titration calorimetry (ITC) studies are combined
      with fold predictions to both define the various interference mechanisms and
      assess the ability of added complementary oligonucleotides to ameliorate them.
      The proposed blocking strategy is thereby refined and then applied to standard
      library forms of benchmark aptamers against human alpha-thrombin, streptavidin,
      and vascular endothelial growth factor (VEGF). In each case, ITC data show that
      the new method effectively removes fixed-region mediated interference effects so
      that the natural binding affinity of the benchmark aptamer is completely
      restored. We further show that the binding affinities of properly functioning
      aptamers within a selection library are not affected by the blocking protocol,
      and that the method can be applied to various common library formats comprised of
      different flanking region sequences. Finally, we present a rapid and inexpensive
      qPCR-based method for determining the mean binding affinity of retained aptamer
      pools and use it to show that introduction of the pre-blocking method into the
      standard SELEX protocol results in retention of high-affinity aptamers that would
      otherwise be lost during the first round of selection. Significant enrichment of
      the available pool of high-affinity aptamers is thereby achieved in the first few
      rounds of selection. By eliminating single-strand (aptamer-like) structures
      within or involving the fixed regions, the technique is therefore shown to
      isolate aptamer sequence and function within the desired random region of the
      library members, and thereby provide a new selection method that is complementary
      to other available SELEX protocols.

PMID- 24895228
TI  - Microstructured graphene arrays for highly sensitive flexible tactile sensors.
AB  - A highly sensitive tactile sensor is devised by applying microstructured graphene
      arrays as sensitive layers. The combination of graphene and anisotropic
      microstructures endows this sensor with an ultra-high sensitivity of -5.53 kPa(
      1) , an ultra-fast response time of only 0.2 ms, as well as good reliability,
      rendering it promising for the application of tactile sensing in artificial skin
      and human-machine interface. 

PMID- 24895229
TI  - Wallerian degeneration and recovery of motor nerves after multiple focused cold
      therapies.
AB  - INTRODUCTION: A device has been developed to apply freezing temperatures to
      temporarily impede nerve conduction, resulting in inhibition of voluntary
      skeletal muscle contraction. This device was designed as an alternative to the
      neurotoxins usually used to treat movement disorders. METHODS: We evaluated the
      effects of single and 3 repeat treatments with a cryoprobe device (-55 degrees C)
      on a sciatic nerve rat model. Long-term effects of repeated treatment were
      evaluated through assessments of physiological function and histological
      analysis. RESULTS: There was consistent weakening of physiological function after
      each treatment, with recovery of normal function by 8 weeks posttreatment.
      Histological findings showed axonal degeneration with no disruption to the
      epineurial or perineurial structures. Progressive axonal regeneration was
      followed by normal recovery by 24 weeks post-treatment. CONCLUSIONS: Low
      temperature treatment of motor nerves did not result in permanent or long-term
      changes to nerve function or structure.

PMID- 24895230
TI  - HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic
      intraoperative intraperitoneal chemoperfusion followed by postoperative
      intravenous platinum-based chemotherapy in patients with platinum-sensitive
      recurrent epithelial ovarian cancer.
AB  - This phase I study tested the safety, feasibility, pharmacokinetics and
      pharmacodynamics of cisplatin administered as hyperthermic intraoperative
      intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive
      recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive
      surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve
      patients with operable, recurrent platinum-sensitive EOC (recurrence >=6 months
      after first-line therapy) were included according to the classical 3+3 dose
      escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical
      cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min
      at 41-43 degrees C. Postoperatively, all patients were treated with standard
      intravenous platinum-based combination chemotherapy. One of six patients
      experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100
      mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their
      treatment well. The recommended phase II dose was established at 100 mg/m(2). The
      mean peritoneal-to-plasma AUC ratio was 19.5 at the highest dose level. Cisplatin
      induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1
      3 toxicities included fatigue, postoperative pain, nausea, and surgical site
      infection. The ability to administer standard intravenous platinum-based
      chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a
      dose of 100 mg/m(2) has an acceptable safety profile in selected patients
      undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC.
      Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin
      were confirmed at all dose levels, especially at 100 mg/m(2). The results are
      encouraging to determine the efficacy of HIPEC as a complementary treatment in
      patients with EOC.

PMID- 24895231
TI  - Molecular mechanism of cholangiocarcinoma carcinogenesis.
AB  - Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with a
      poor prognosis, which often arises from conditions causing long-term
      inflammation, injury, and reparative biliary epithelial cell proliferation.
      Several conditions are known to be major risk factors for cancer in the biliary
      tract or gallbladder, including primary sclerosing cholangitis, liver fluke
      infection, pancreaticobiliary maljunction, and chemical exposure in proof
      printing workers. Abnormalities in various signaling cascades, molecules, and
      genetic mutations are involved in the pathogenesis of CCA. CCA is characterized
      by a series of highly recurrent mutations in genes, including KRAS, BRF, TP53,
      Smad, and p16(INK4a) . Cytokines that are affected by inflammatory environmental
      conditions, such as interleukin-6 (IL-6), transforming growth factor-beta (TGF
      beta), tumor necrosis factor-alpha (TNF-alpha), and platelet-derived growth
      factor (PDGF), play an important role in cancer pathogenesis. Prominent signaling
      pathways important in carcinogenesis include TGF-beta/Smad, IL-6/STAT-3,
      PI3K/AKT, Wnt, RAF/MEK/MAPK, and Notch. Additionally, some microRNAs regulate
      targets in critical pathways of CCA development and progression. This review
      article provides the understanding of the genetic and epigenetic mechanism(s) of
      carcinogenesis in CCA, which leads to the development of new therapeutic targets
      for the prevention and treatment of this devastating cancer. 

PMID- 24895232
TI  - Pomegranate juice and prostate cancer: importance of the characterisation of the
      active principle.
AB  - Two exploratory clinical studies investigating proprietary pomegranate products
      showed a trend of effectiveness in increasing prostate-specific antigen doubling
      time in patients with prostate cancer. A recent clinical study did not support
      these results. We therefore analysed a lot of the marketed pomegranate blend for
      co-active pomegranate compounds. The high-performance liquid chromatography
      method was used to detect punicalagin, ellagic acid and anthocyanins. Total
      polyphenoles were determined by the Folin-Ciocalteu method using gallic acid as
      reference. The results show that the co-active compounds in the daily dose of the
      pomegranate blend were far below those previously tested and that the photometric
      assessment is not reliable for the standardisation of study medications. Not
      pomegranate but the low amount of co-active compounds in the proprietary
      pomegranate blend was responsible for its clinical ineffectiveness.

PMID- 24895233
TI  - Thermophoresis in nanoliter droplets to quantify aptamer binding.
AB  - Biomolecule interactions are central to pharmacology and diagnostics. These
      interactions can be quantified by thermophoresis, the directed molecule movement
      along a temperature gradient. It is sensitive to binding induced changes in size,
      charge, or conformation. Established capillary measurements require at least 0.5
      MUL per sample. We cut down sample consumption by a factor of 50, using 10 nL
      droplets produced with acoustic droplet robotics (Labcyte). Droplets were
      stabilized in an oil-surfactant mix and locally heated with an IR laser.
      Temperature increase, Marangoni flow, and concentration distribution were
      analyzed by fluorescence microscopy and numerical simulation. In 10 nL droplets,
      we quantified AMP-aptamer affinity, cooperativity, and buffer dependence.
      Miniaturization and the 1536-well plate format make the method high-throughput
      and automation friendly. This promotes innovative applications for diagnostic
      assays in human serum or label-free drug discovery screening. 

PMID- 24895234
TI  - Balloon assisted tracking: a double edged sword.

PMID- 24895235
TI  - Pharmacoeconomic evaluation of dabigatran, rivaroxaban and apixaban versus
      enoxaparin for the prevention of venous thromboembolism after total hip or knee
      replacement in Spain.
AB  - BACKGROUND: Patients undergoing total hip replacement (THR) or total knee
      replacement (TKR) surgery are at high risk of developing venous thromboembolism
      (VTE). Thromboprophylaxis with low-molecular-weight heparin, such as enoxaparin,
      is standard of care in these patients. Recently, three direct oral anticoagulants
      (DOACs; dabigatran, rivaroxaban and apixaban), have been approved for this
      indication, but their cost effectiveness is still unclear as it has usually been
      extrapolated from surrogate venographic outcomes in clinical trials. OBJECTIVE:
      To conduct a pharmacoeconomic evaluation of the DOACs versus subcutaneous (SC)
      enoxaparin for the prevention of VTE after THR or TKR surgery. METHODS: A
      decision-tree model was developed using TreeAge Pro 2011 to compare the cost
      utility and cost effectiveness of the DOACs with SC enoxaparin, with separate
      models for THR and TKR over a 3-month postoperative time horizon from the
      perspective of the Spanish National Health System. The probabilities of events
      (symptomatic VTE, clinically relevant bleedings, heparin-induced thrombocytopenia
      and deaths) were derived from a systematic review and meta-analysis. We used
      local cost estimates (?2013) and utility values were obtained from the
      literature. We reported costs, quality-adjusted life-years (QALYs) and
      symptomatic VTE events. We conducted sensitivity analyses to evaluate parameter
      uncertainty. RESULTS: The average costs per 1,000 patients treated with
      enoxaparin were higher than costs incurred by dabigatran, rivaroxaban and
      apixaban in THR (?435,208 vs. ?283,574, ?257,900 and ?212,472, respectively) and
      TKR (?336,550 vs. ?219,856, ?251,734 and ?201,946, respectively), with cost
      savings ranging from ?151,634 to ?222,766 in THR, and from ?84,816 to ?134,604 in
      TKR. Cost differences were largely driven by differences in costs associated with
      drug administration. The average QALYs per 1,000 patients treated were very
      similar for enoxaparin, dabigatran, rivaroxaban and apixaban in THR (199.34,
      198.83, 199.08 and 199.68, respectively) and TKR (198.95, 199.41, 198.75 and
      199.97, respectively). Rivaroxaban (in TKR and THR) and apixaban (in THR) avoided
      additional symptomatic VTE events compared with enoxaparin. Sensitivity analyses
      generally supported the robustness of the analysis to changes in model
      parameters. CONCLUSIONS: Our model suggests, based on its underlying assumptions
      and data, that the DOACs are cost-saving alternatives to SC enoxaparin for the
      prevention of VTE after THR or TKR, in the Spanish healthcare setting.

PMID- 24895237
TI  - A biomimetic honeycomb-like scaffold prepared by flow-focusing technology for
      cartilage regeneration.
AB  - A tissue engineering chondrocytes/scaffold construct provides a promise to
      cartilage regeneration. The architecture of a scaffold such as interconnections,
      porosities, and pore sizes influences the fates of seeding cells including gene
      expression, survival, migration, proliferation, and differentiation thus may
      determine the success of this approach. Scaffolds of highly ordered and uniform
      structures are desirable to control cellular behaviors. In this study, a newly
      designed microfluidic device based on flow-focusing geometry was developed to
      fabricate gelatin scaffolds of ordered pores. In comparison with random foam
      scaffolds made by the conventional freeze-dried method, honeycomb-like scaffolds
      exhibit higher swelling ratio, porosity, and comparable compressive strength. In
      addition, chondrocytes grown in the honeycomb-like scaffolds had good cell
      viability, survival rate, glycosaminoglycans production, and a better
      proliferation than ones in freeze-dried scaffolds. Real-time PCR analysis showed
      that the mRNA expressions of aggrecan and collagen type II were up-regulated when
      chondrocytes cultured in honeycomb-like scaffolds rather than cells cultured as
      monolayer fashion. Oppositely, chondrocytes expressed collagen type II as
      monolayer culture when seeded in freeze-dried scaffolds. Histologic examinations
      revealed that cells produced proteoglycan and distributed uniformly in honeycomb
      like scaffolds. Immunostaining showed protein expression of S-100 and collagen
      type II but negative for collagen type I and X, which represents the chondrocytes
      maintained normal phenotype. In conclusion, a highly ordered and honeycomb-like
      scaffold shows superior performance in cartilage tissue engineering. Biotechnol.
      Bioeng. 2014;111: 2338-2348. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24895236
TI  - Molecular and cellular immune responses to ischemic brain injury.
AB  - Despite extensive research into stroke pathology, there have not been any major
      recent advancements in stroke therapeutics. Animal models of cerebral ischemia
      and clinical data have been used to investigate the progressive neural injury
      that occurs after an initial ischemic insult. This has lead researchers to focus
      more on the peripheral immune response that is generated as a result of cerebral
      ischemia. The therapies that have been developed as a result of this research
      thus far have proven ineffective in clinical trials. The failure of these
      therapeutics in clinical trials is thought to be due to the broad
      immunosuppression elicited as a result of the treatments and the cerebral
      ischemia itself. Emerging evidence indicates a more selective modulation of the
      immune system following stroke could be beneficial. The spleen has been shown to
      exacerbate neural injury following experimental stroke and would provide a strong
      therapeutic target. Selecting facets of the immune system to target would allow
      the protective and regenerative properties of the immune response to remain
      intact while blunting the pro-inflammatory response generated towards the injured
      brain. 

PMID- 24895238
TI  - Quick identification of xanthine oxidase inhibitor and antioxidant from Erycibe
      obtusifolia by a drug discovery platform composed of multiple mass spectrometric
      platforms and thin-layer chromatography bioautography.
AB  - As a final step of the purine metabolism process, xanthine oxidase catalyzes the
      oxidation of hypoxanthine and xanthine into uric acid. Our research has
      demonstrated that Erycibe obtusifolia has xanthine oxidase inhibitory properties.
      The purpose of this paper is to describe a new strategy based on a combination of
      multiple mass spectrometric platforms and thin-layer chromatography bioautography
      for effectively screening the xanthine oxidase inhibitory and antioxidant
      properties of E. obtusifolia. This strategy was accomplished through the
      following steps. (i) Separate the extract of E. obtusifolia into fractions by an
      autopurification system controlled by liquid chromatography with mass
      spectrometry. (ii) Determine the active fractions of E. obtusifolia by thin-layer
      chromatography bioautography. (iii) Identify the structure of the main active
      compounds with the information provided by direct analysis in real time mass
      spectrometry. (iv) Calculate the IC50 value of each compound against xanthine
      oxidase using high-performance liquid chromatography. Using the caulis of E.
      obtusifolia as the experimental material, seven target peaks were screened out as
      xanthine oxidase inhibitors or antioxidants. Our screening strategy allows for
      rapid analysis of small molecules with almost no sample preparation and can be
      completed within a week, making it a useful assay to identify unstable compounds
      and provide the empirical foundation for E. obtusifolia as a natural remedy for
      gout and oxidative-stress-related diseases. 

PMID- 24895239
TI  - Combining MRI and muscle biopsy improves diagnostic accuracy in subacute-onset
      idiopathic inflammatory myopathy.
AB  - INTRODUCTION: In 10-20% of patients with subacute-onset idiopathic inflammatory
      myopathy (IIM), muscle biopsy is normal or shows nonspecific findings. MRI can be
      used as a triage test before muscle biopsy and as an add-on test if the biopsy is
      nondiagnostic. METHODS: MRI scans of skeletal muscles and muscle biopsies were
      evaluated prospectively in 48 patients suspected to have IIM. The interpretations
      of MRI and muscle biopsy were compared with the definite diagnosis (based on
      European Neuromuscular Centre criteria and response to corticosteroids). RESULTS:
      The false negative rate (FNR) of all muscle biopsies was 0.23. Biopsies of a
      muscle showing hyperintensity on MRI (as triage test) had an FNR of 0.19. The
      result of MRI as an add-on test in patients with a nondiagnostic muscle biopsy
      decreased the FNR from 0.23 to 0.06. CONCLUSIONS: We recommend both MRI and
      muscle biopsy in patients suspected of having IIM.

PMID- 24895241
TI  - Body-size throughout life and risk of depression in postmenopausal women:
      findings from the E3N cohort.
AB  - OBJECTIVE: To assess the association of body-size from childhood to age 40 with
      depression in postmenopausal French women. METHODS: Participants of the E3N study
      reported birth characteristics and silhouettes matching theirs at age 8, at
      puberty, at 20-25, and 35-40 years (n = 41,144). Depression was assessed by the
      Center for Epidemiological Studies Depression Scale and split into new-onset and
      recurrent depression according to women's history of psychological disorder.
      Risks were estimated with multinomial logistic regression models. RESULTS: Low or
      high birth weights were associated with risk of depression. A large body-size at
      age 8 and a large body-size over the life-course were both associated with the
      risk of new-onset depression specifically, while women with a large body-size
      increase at puberty were at risk of recurrent depression. Largest body-sizes at
      20-25 or 35-40 years were associated with both the risk of new-onset and
      recurrent depression, especially in normal weight women. However, a lean
      silhouette at 35-40 years was associated with the risk of recurrent depression
      only. CONCLUSIONS: Women with a large body-size from childhood to adulthood might
      be at higher risk of new-onset postmenopausal depression, while leanness in
      adulthood could be associated with a higher risk of recurrent depression.

PMID- 24895242
TI  - Black tea extract and its thearubigins relieve the sildenafil-induced delayed gut
      motility in mice: a possible role of nitric oxide.
AB  - In this study we hypothesize that a standardized black tea aqueous extract (BTE)
      and thearubigins, its main polyphenolic pigments, will improve sildenafil-induced
      delay in gastric emptying (GE) and small intestinal transit (SIT) in mice. Twenty
      groups of mice (n = 8) were given a phenol red meal, and three sets of
      experiments were performed. In the first and second sets, effects of different
      concentrations of BTE, thearubigins (TRs), and sildenafil (SLD), alone and in
      combinations, on GE and SIT were measured. In the third set, influence of nomega 
      Nitro-l-arginine methyl ester hydrochloride (l-NAME) pretreatment on effects of
      these treatments was tested. Black tea extract (3% and 4.5%) and thearubigins (50
      and 60 mg/kg) dose-dependently increased GE and SIT, whereas BTE 6% and
      thearubigins 70 mg/kg did not affect them. Sildenafil dose-dependently reduced
      both GE and SIT. Combination of metoclopramide, BTE 4.5%, thearubigins 60, or l
      NAME with sildenafil (5 mg/kg) reversed its motility-delaying effects.
      Pretreatment with l-NAME followed by BTE 4.5%, thearubigins 60, BTE 4.5% +
      sildenafil 5, or thearubigins 60 + sildenafil 5 only partially affected the
      accelerating effects of BTE 4.5% and thearubigins 60. In conclusion, a
      standardized BTE and its thearubigins improve the sildenafil-induced delayed gut
      motility in mice. This improvement was partially blocked by l-NAME suggesting a
      possible role of nitric oxide. Thus, BTE 4.5% or TRs 60 mg/kg solution could be
      considered a reliever therapy for the sildenafil-induced dyspepsia.

PMID- 24895243
TI  - Phosphine-directed C-H borylation reactions: facile and selective access to
      ambiphilic phosphine boronate esters.
AB  - Ambiphilic ligands have received considerable attention over the last two decades
      due to their unique reactivity as organocatalysts and ligands. The iridium
      catalyzed C-H borylation of phosphines is described in which the phosphine is
      used as a directing group to provide selective formation of arylboronate esters
      with unique scaffolds of ambiphilic compounds. A variety of aryl and benzylic
      phosphines were subjected to the reaction conditions, selectively providing
      stable, isolable boronate esters upon protection of the phosphine as the borane
      complex. After purification, the phosphine-substituted boronate esters could be
      deprotected and isolated in pure form.

PMID- 24895240
TI  - Nuclear receptors and the Warburg effect in cancer.
AB  - In 1927 Otto Warburg established that tumours derive energy primarily from the
      conversion of glucose to lactic acid and only partially through cellular
      respiration involving oxygen. In the 1950s he proposed that all causes of cancer
      reflected different mechanisms of disabling cellular respiration in favour of
      fermentation (now termed aerobic glycolysis). The role of aberrant glucose
      metabolism in cancer is now firmly established. The shift away from oxidative
      phosphorylation towards the metabolically expensive aerobic glycolysis is
      somewhat counter-intuitive given its wasteful nature. Multiple control processes
      are in place to maintain cellular efficiency and it is likely that these
      mechanisms are disrupted to facilitate the shift to the reliance on aerobic
      glycolysis. One such process of cell control is mediated by the nuclear receptor
      superfamily. This large family of transcription factors plays a significant role
      in sensing environmental cues and controlling decisions on proliferation,
      differentiation and cell death for example, to regulate glucose uptake and
      metabolism and to modulate the actions of oncogenes and tumour suppressors. In
      this review we highlight mechanisms by which nuclear receptors actions are
      altered during tumorigenic transformation and can serve to enhance the shift to
      aerobic glycolysis. At the simplest level, a basic alteration in NR behaviour can
      serve to enhance glycolytic flux thus providing a basis for enhanced survival
      within the tumour micro-environment. Ameliorating the enhanced NR activity in
      this context may help to sensitize cancer cells to Warburg targeted therapies and
      may provide future drug targets. 

PMID- 24895244
TI  - Coordination pattern variability provides functional adaptations to constraints
      in swimming performance.
AB  - In a biophysical approach to the study of swimming performance (blending
      biomechanics and bioenergetics), inter-limb coordination is typically considered
      and analysed to improve propulsion and propelling efficiency. In this approach,
      'opposition' or 'continuous' patterns of inter-limb coordination, where
      continuity between propulsive actions occurs, are promoted in the acquisition of
      expertise. Indeed a 'continuous' pattern theoretically minimizes intra-cyclic
      speed variations of the centre of mass. Consequently, it may also minimize the
      energy cost of locomotion. However, in skilled swimming performance there is a
      need to strike a delicate balance between inter-limb coordination pattern
      stability and variability, suggesting the absence of an 'ideal' pattern of
      coordination toward which all swimmers must converge or seek to imitate. Instead,
      an ecological dynamics framework advocates that there is an intertwined
      relationship between the specific intentions, perceptions and actions of
      individual swimmers, which constrains this relationship between coordination
      pattern stability and variability. This perspective explains how behaviours
      emerge from a set of interacting constraints, which each swimmer has to satisfy
      in order to achieve specific task performance goals and produce particular task
      outcomes. This overview updates understanding on inter-limb coordination in
      swimming to analyse the relationship between coordination variability and
      stability in relation to interacting constraints (related to task, environment
      and organism) that swimmers may encounter during training and performance. 

PMID- 24895245
TI  - Impaired peripheral glucose sensing in F1 offspring of diabetic pregnancy.
AB  - Maternal diabetes can induce permanent changes in glucose homeostasis that can
      occur pre- and post-natal and leads to type 2 diabetes in adulthood. This study
      aimed to investigate the effect of maternal diabetes on the F1 offspring
      peripheral glucose sensing and mitochondrial biogenesis in an attempt to clarify
      the mechanism of diabetogenic programming. Two groups of female Wistar rats were
      used (diabetic and control); diabetes was neonatally induced by STZ injection to
      5-day old rats. After the pregnancy and delivery, the offspring were weaned to
      control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5
      weeks, OGTT was constructed, and serum and tissues were obtained for the
      assessment of mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor
      (phospho-IR), and GLUT4. The result indicated impaired glucose tolerance (IGT)
      and insulin resistance in the offspring under control diet at the 15th week of
      age and thereafter while those offspring under HCD showed IGT at 10th week, and
      diabetes was evidenced at the 25th week of age. This defect in glucose metabolism
      was preceded by impairment in the phosphorylation of IR and decreased IR and
      Glut4 that cause impaired glucose sensing together with inhibited mitochondrial
      biogenesis in muscle and adipose tissues. This study indicated that maternal
      diabetes caused impaired glucose sensing and insulin resistance in the peripheral
      tissues and caused change in the expression of genes involved in mitochondrial
      biogenesis and function. Post-natal feeding with HCD may accelerate these
      changes. Male F1 offspring appears to be more sensitive than females for fetal
      programming of T2D.

PMID- 24895246
TI  - Biofilm growth of Chlorella sorokiniana in a rotating biological contactor based
      photobioreactor.
AB  - Microalgae biofilms could be used as a production platform for microalgae
      biomass. In this study, a photobioreactor design based on a rotating biological
      contactor (RBC) was used as a production platform for microalgae biomass
      cultivated in biofilm. In the photobioreactor, referred to as Algadisk,
      microalgae grow in biofilm on vertical rotating disks partially submerged in a
      growth medium. The objective is to evaluate the potential of the Algadisk
      photobioreactor with respect to the effects of disk roughness, disk rotation
      speed and CO2 concentration. These objectives where evaluated in relationship to
      productivity, photosynthetic efficiency, and long-term cultivation stability in a
      lab-scale Algadisk system. Although the lab-scale Algadisk system is used,
      operation parameters evaluated are relevant for scale-up. Chlorella Sorokiniana
      was used as model microalgae. In the lab-scale Algadisk reactor, productivity of
      20.1 +/- 0.7 g per m(2) disk surface per day and a biomass yield on light of 0.9
      +/- 0.04 g dry weight biomass per mol photons were obtained. Different disk
      rotation speeds did demonstrate minimal effects on biofilm growth and on the
      diffusion of substrate into the biofilm. CO2 limitation, however, drastically
      reduced productivity to 2-4 g per m(2) disk surface per day. Productivity could
      be maintained over a period of 21 weeks without re-inoculation of the Algadisk.
      Productivity decreased under extreme conditions such as pH 9-10, temperature
      above 40 degrees C, and with low CO2 concentrations. Maximal productivity,
      however, was promptly recovered when optimal cultivation conditions were
      reinstated. These results exhibit an apparent opportunity to employ the Algadisk
      photobioreactor at large scale for microalgae biomass production if diffusion
      does not limit the CO2 supply.

PMID- 24895248
TI  - Simultaneous determination of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L
      arginine, N(G),N(G')-dimethyl-L-arginine, and L-arginine using monolithic silica
      disk-packed spin columns and a monolithic silica column.
AB  - We have developed and validated a high-performance liquid chromatography method
      that uses monolithic silica disk-packed spin columns and a monolithic silica
      column for the simultaneous determination of N(G)-monomethyl-L-arginine,
      N(G),N(G)-dimethyl-L-arginine, and N(G),N(G')-dimethyl-L-arginine in human
      plasma. For solid-phase extraction, our method employs a centrifugal spin column
      packed with monolithic silica bonded to propyl benzenesulfonic acid as a cation
      exchanger. After pretreatment, the methylated arginines are converted to
      fluorescent derivatives with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, and then the
      derivatives are separated on a monolithic silica column. L-arginine concentration
      was also determined in diluted samples. Standard calibration curves revealed that
      the assay was linear in the concentration range 0.2-1.0 MUM for methylated
      arginines and 40-200 MUM for L-arginine. Linear regression of the calibration
      curve yielded equations with correlation coefficients of 0.999 (r(2)). The
      sensitivity was satisfactory, with a limit of detection ranging from 3.75 to 9.0
      fmol for all four compounds. The RSDs were 4.3-4.8% (intraday) and 3.0-6.8%
      (interday). When this method was applied to samples from six healthy donors, the
      detected concentrations of N(G)-monomethyl-L-arginine, N(G),N(G)-dimethyl-L
      arginine, N(G),N(G')-dimethyl-L-arginine and L-arginine were 0.05 +/- 0.01, 0.41
      +/- 0.07, 0.59 +/- 0.11, and 83.8 +/- 30.43 MUM (n = 6), respectively.

PMID- 24895250
TI  - Bill to protect doctors who try experimental treatments starts journey through UK
      parliament.

PMID- 24895249
TI  - Patient perception of pain versus observed pain behavior during a standardized
      electrodiagnostic test.
AB  - INTRODUCTION: Clinicians often assume that observations of pain behavior are
      adequate for assessment of patient pain perception during procedures. This has
      not been tested during a standardized electrodiagnostic experience. METHODS:
      During a prospective trial including extensive, standardized electrodiagnostic
      testing on persons with lumbar stenosis, vascular claudication, and asymptomatic
      volunteers, the subjects and an observer rated levels of pain. RESULTS: In 60
      subjects, observers significantly under-rated pain (Visual Analog Scale 3.17 +/-
      2.23 vs. 4.38 +/- 2.01, t = -4.577, df = 59, P < 0.001). Perceived pain during
      testing related to bodily pain as measured by the visual analog, McGill, Pain
      Disability, and Quebec scales, but not age, duration of symptoms, Tampa
      kinesiphobia, Center for Epidemiological Studies Depression scale, or SF-36
      health quality of life. CONCLUSIONS: Persons with worse pain syndromes may
      perceive more pain during testing than others. Clinicians and researchers should
      understand that patients may have more pain than they recognize.

PMID- 24895247
TI  - The potential role of lung microbiota in lung cancer attributed to household coal
      burning exposures.
AB  - Bacteria influence site-specific disease etiology and the host's ability to
      metabolize xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs). Lung
      cancer in Xuanwei, China has been attributed to PAH-rich household air pollution
      from burning coal. This study seeks to explore the role of lung microbiota in
      lung cancer among never smoking Xuanwei women and how coal burning may influence
      these associations. DNA from sputum and buccal samples of never smoking lung
      cancer cases (n = 8, in duplicate) and controls (n = 8, in duplicate) in two
      Xuanwei villages was extracted using a multi-step enzymatic and physical lysis,
      followed by a standardized clean-up. V1-V2 regions of 16S rRNA genes were PCR
      amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing
      and high-quality sequences were evaluated for diversity and taxonomic membership.
      Bacterial diversity among cases and controls was similar in buccal samples (P =
      0.46), but significantly different in sputum samples (P = 0.038). In sputum,
      Granulicatella (6.1 vs. 2.0%; P = 0.0016), Abiotrophia (1.5 vs. 0.085%; P =
      0.0036), and Streptococcus (40.1 vs. 19.8%; P = 0.0142) were enriched in cases
      compared with controls. Sputum samples had on average 488.25 species-level OTUs
      in the flora of cases who used smoky coal (PAH-rich) compared with 352.5 OTUs
      among cases who used smokeless coal (PAH-poor; P = 0.047). These differences were
      explained by the Bacilli species (Streptococcus infantis and Streptococcus
      anginosus). Our small study suggests that never smoking lung cancer cases have
      differing sputum microbiota than controls. Further, bacteria found in sputum may
      be influenced by environmental exposures associated with the type of coal burned
      in the home.

PMID- 24895251
TI  - Molecular mechanisms and anti-cancer aspects of the medicinal phytochemicals
      rocaglamides (=flavaglines).
AB  - Rocaglamides (= flavaglines) are potent natural anti-cancer phytochemicals that
      inhibit cancer growth at nanomolar concentrations by the following mechanisms:
      (1) inhibition of translation initiation via inhibition of phosphorylation of the
      mRNA cap-binding eukaryotic translation initiation factor eIF4E and stabilization
      of RNA-binding of the translation initiation factor eIF4A in the eIF4F complex;
      (2) blocking cell cycle progression by activation of the ATM/ATR-Chk1/Chk2
      checkpoint pathway; (3) inactivation of the heat shock factor 1 (HSF1) leading to
      up-regulation of thioredoxin-interacting protein (TXNIP) and consequent reduction
      of glucose uptake and (4) induction of apoptosis through activation of the MAPK
      p38 and JNK and inhibition of the Ras-CRaf-MEK-ERK signaling pathway. Besides the
      anti-cancer activities, rocaglamides are also shown to protect primary cells from
      chemotherapy-induced cell death and alleviate inflammation- and drug-induced
      injury in neuronal tissues. This review will focus on the recently discovered
      molecular mechanisms of the actions of rocaglamides and highlights the benefits
      of using rocaglamides in cancer treatment. 

PMID- 24895253
TI  - Dispatch from the field: is mathematical modeling applicable to obesity treatment
      in the real world?

PMID- 24895252
TI  - MRI measures of corpus callosum iron and myelin in early Huntington's disease.
AB  - Increased iron in subcortical gray matter (GM) structures of patients with
      Huntington's disease (HD) has been suggested as a causal factor in neuronal
      degeneration. But how iron content is related to white matter (WM) changes in HD
      is still unknown. For example, it is not clear whether WM changes share the same
      physiopathology (i.e. iron accumulation) with GM or whether there is a different
      mechanism. The present study used MRI to examine iron content in premanifest gene
      carriers (PreHD, n = 25) and in early HD patients (n = 25) compared with healthy
      controls (n = 50). 3T MRI acquisitions included high resolution 3D T1, EPI
      sequences for diffusion tensor imaging (DTI) as an indirect measure of tissue
      integrity, and T2*-weighted gradient echo-planar imaging for MR-based relaxometry
      (R2*), which provides an indirect measure of ferritin/iron deposition in the
      brain. Myelin breakdown starts in the PreHD stage, but there is no difference in
      iron content values. Iron content reduction manifests later, in the early HD
      stage, in which we found a lower R2* parameter value in the isthmus. The WM iron
      reduction in HD is temporally well-defined (no iron differences in PreHD subjects
      and iron differences only in early HD patients). Iron level in callosal WM may be
      regarded as a marker of disease state, as iron does not differentiate PreHD
      subjects from controls but distinguishes between PreHD and HD.

PMID- 24895254
TI  - Structural characterization of secoiridoid glycosides by high-performance liquid
      chromatography/electrospray ionization mass spectrometry.
AB  - RATIONALE: The fragmentation behavior of seven secoiridoid glycosides (SIGs)
      isolated from Gentiana triflora Pall., a traditional Chinese medicine, was
      investigated by electrospray ionization ion trap mass spectrometry (ESI-IT-MS).
      METHODS: Multistage electrospray ionization mass spectrometry (ESI-MS(n))
      experiments both in positive- and negative-ion mode were used to elucidate the
      main fragmentation pathways of these compounds. RESULTS: In full scan mass
      spectra, different deprotonated or protonated molecules were observed for
      compounds with different basic structure. Ring cleavages of the aglycon moiety
      were observed in MS(2) spectra and the characteristic ions provided valuable
      information on the basic structural skeletons. Their fragmentation pathways and
      fragment ion structures were proposed. CONCLUSIONS: The established fragmentation
      patterns have been successfully used to identify eleven SIGs in the extract of
      Gentiana triflora Pall.

PMID- 24895255
TI  - Electron attachment to some naphthoquinone derivatives: long-lived molecular
      anion formation.
AB  - RATIONALE: Electron Affinity (EA) is one of the fundamental properties of a
      molecule. EA values can be measured with various experimental methods, although
      their availability is still relatively limited. We make an attempt to use
      Dissociative Electron Attachment Spectroscopy (DEAS) data for evaluation of the
      EAs of twelve naphthoquinone (NQ) derivatives. METHODS: Naphthoquinone (NQ) and
      eleven of its hydroxyl derivatives were investigated by means of DEAS. A combined
      investigation of NQ and juglone by means of the Electron Transmission
      Spectroscopy (ETS) and DEAS techniques, with the support of density functional
      theory (DFT) calculations, allowed us to elucidate the empty-level structures of
      NQ and its hydroxyl derivatives. RESULTS: All molecules under investigation form
      extremely long-lived molecular anions associated with three resonant states
      (except for NQ, where only two long-lived resonances were observed). The hydroxyl
      substituents of NQ cause an increase in EA and number of internal degrees of
      freedom (N), and, as a result, an increase in the mean electron autodetachment
      lifetimes of the molecular negative ions (NIs). Evaluation of the EAs from the
      measured lifetimes of the molecular NIs through a simple Arrhenius approximation
      gives results in reasonable agreement with those obtained with DFT calculations.
      CONCLUSIONS: NI lifetime measurements by means of a modified DEAS instrumentation
      can provide quantitative data of EA. A simple Arrhenius approximation seems to be
      adequate to describe the process of electron detachment from molecular anions.

PMID- 24895256
TI  - Capillary atmospheric pressure chemical ionization using liquid point electrodes.
AB  - RATIONALE: Atmospheric pressure chemical ionization (APCI) sources operated with
      point to plane DC discharges ('Coronas') frequently suffer from point electrode
      degradation and potentially lead to oxidation and/or fragmentation of the
      generated analyte ions. It is postulated that these adverse effects are caused by
      the interaction of these ions with the discharge chemistry as well as en route to
      the mass analyzer region. METHODS: The corona discharge metal point electrode is
      replaced by the conically shaped liquid effluent evolving from a fused-silica
      capillary, which is analogous but not identical to the Taylor cone formation in
      electrospray ionization. The liquid consisting of either pure water or water
      containing 0.1 %V formic acid is fed via a nano-flow delivery stage at typical
      flow rates between 1-800 MUL/h. The liquid flow is continuously replenishing the
      surface of the point electrode. The source is directly coupled to the inlet
      capillary of appropriate mass spectrometers, e.g., the Bruker Daltonics and
      Agilent varieties. RESULTS: The actively pumped liquid flow is supplying a
      constant amount of the reagent gas (H2O) to the corona region in the 20 ppmV to
      30 %V range, leading to controlled, very stable operation of the source. The
      typical light emission observed for corona discharges is in very close proximity
      to the aqueous surface. Analyte protonation is the dominating ionization pathway.
      The degree of primary analyte fragmentation is extremely low. CONCLUSIONS: We
      have developed a novel atmospheric pressure chemical ionization source designed
      for the hyphenation of nano-flow liquid chromatography and gas chromatography
      with atmospheric pressure ionization mass spectrometry. The proposed reaction
      mechanism including the electrochemistry occurring in the source along with
      formation of protonated analyte molecules via collision-induced dissociation
      (CID) is in full accord with the experimental results. The system exhibits an
      extremely stable performance over prolonged operation times, sole generation of
      protonated molecules, and low degree of analyte ion fragmentation.

PMID- 24895257
TI  - Generation of Au(p)Ag(q)Te(r) clusters via laser ablation synthesis using Au-Ag
      Te nano-composite as precursor: quadrupole ion-trap time-of-flight mass
      spectrometry.
AB  - RATIONALE: Metal tellurides have applications in various fields of science and
      technology but only a few gold-silver tellurides have been reported. The laser
      ablation synthesis (LAS) method allows the preparation of nano-materials from
      solid substrates. Therefore, this method was selected to synthesise some gold
      silver tellurides. METHODS: Laser desorption ionisation quadrupole ion trap time
      of-flight mass spectrometry (LDI QIT TOF MS) was used for the generation of new
      Au(p)Ag(q)Te(r) clusters. Scanning electron microscopy (SEM) and energy
      dispersive X-ray spectroscopy (EDX) were used to characterise the materials. The
      stoichiometry of the clusters generated was determined via collision-induced
      dissociation (CID) and modeling of isotopic patterns. RESULTS: Chemisorption of
      gold and silver nano-particles on tellurium powder led to the formation of a new
      kind of Au-Ag-Te nano-composite. The LDI of this nano-composite yielded nine
      unary (Ag(q), Te(r)), 40 binary (Au(p)Te(r) and Ag(p)Te(r)) and 78 ternary
      clusters. The stoichiometry of these novel Au(p)Ag(q)Te(r) clusters is reported
      here for the first time. CONCLUSIONS: The new Au-Ag-Te nano-composite was found
      to be a more suitable precursor for the generation of clusters than the mixtures
      of the elements. TOF MS was shown to be a useful technique for following the
      generation of gold-silver tellurides. Knowledge of the cluster stoichiometry
      could accelerate the further development of novel high-tech materials such as
      chalcogenide glasses.

PMID- 24895258
TI  - Transformation of codeine and codeine-6-glucuronide to opioid analogues by urine
      adulteration with pyridinium chlorochromate: potential issue for urine drug
      testing.
AB  - RATIONALE: Pyridinium chlorochromate (PCC) is the active ingredient of 'Urine
      Luck', a commercially available in vitro adulterating agent used to conceal the
      presence of drugs in a urine specimen. The exposure of codeine and its major
      glucuronide metabolite codeine-6-glucuronide (C6G) to PCC was investigated to
      determine whether PCC is an effective masking agent for these opiate compounds.
      METHODS: Following the addition of PCC to both spiked and authentic codeine and
      C6G-positive urine specimens, the samples were monitored using liquid
      chromatography/mass spectrometry (LC/MS). Stable reaction products were
      identified and characterized using high-resolution MS analysis and, where
      possible, nuclear magnetic resonance (NMR) analysis. RESULTS: It was determined
      that PCC effectively oxidizes codeine and C6G, thus altering the original codeine
      to-C6G ratio in the urine specimen. Four reaction products were identified for
      codeine: codeinone, 14-hydroxycodeinone, 6-O-methylcodeine and 8-hydroxy-7,8
      dihydrocodeinone. Similarly, three reaction products were identified for C6G:
      codeinone, codeine and a lactone of C6G (tentative assignment). CONCLUSIONS:
      Besides addressing the complications added to interpretation, more investigation
      is warranted to further determine their potential for use as markers for
      monitoring the presence of codeine and C6G in urine specimens adulterated with
      PCC.

PMID- 24895259
TI  - Indole-diterpenoid profiles of Claviceps paspali and Claviceps purpurea from high
      resolution Fourier transform Orbitrap mass spectrometry.
AB  - RATIONALE: The biological activities most commonly associated with indole
      diterpenoids are tremorgenicity in mammals and toxicity in insects through
      modulation of ion channels. The neurotoxic effects of some analogues are the
      cause of syndromes such as 'ryegrass staggers' and 'Paspalum staggers' in cattle
      and sheep. Our purpose was to obtain and interpret mass spectra of some pure
      Claviceps-related indole-diterpenoids (paspaline, paspalinine, paxilline,
      paspalitrems A and B) to facilitate identification of related compounds for which
      standards were not available. METHODS: C. paspali-infected Paspalum dilatatum as
      well as C. purpurea sclerotia obtained from infected Phalaris arundinacea were
      extracted and the extracts separated via liquid chromatography. Low- and high
      resolution mass spectra were then obtained of known and potentially unknown
      indole-diterpenoids. RESULTS: At least 20 different indole-diterpenoids were
      detected in the C. paspali extract with molecular masses ranging from 405 Da
      (C28H40NO) to 517 Da (C32H40NO5). The C. purpurea sclerotia were shown to contain
      several indole-diterpenoids with molecular masses ranging from 405 Da (C28H40NO)
      to 419 Da (C28H38NO2). CONCLUSIONS: This study demonstrates for the first time
      that C. purpurea may also produce indole-diterpenoids. This might explain why
      grazing of Phalaris spp. is occasionally connected with a tremorgenic syndrome in
      cattle, called 'phalaris staggers'.

PMID- 24895260
TI  - Maternal plasma phospholipids are altered in trisomy 21 cases and prior to
      preeclampsia and preterm outcomes.

PMID- 24895263
TI  - Mammogram debate flares up: Latest breast cancer screening study fuels
      controversy.

PMID- 24895262
TI  - Unprecedented strong Lewis bases--synthesis and methyl cation affinities of
      dimethylamino-substituted terpyridines.
AB  - A versatile method for the synthesis of functionalized 2,2':6',2''-terpyridines
      by assembly of the terminal pyridine rings is presented. The cyclization
      precursors-bis-beta-ketoenamides-are prepared from 4-substituted 2,6
      pyridinedicarboxylic acids and acetylacetone or its corresponding enamino ketone.
      Treatment with trimethylsilyl trifluoromethanesulfonate induces a twofold
      intramolecular condensation providing an efficient access to 4,4''-di- and
      4,4',4''-trifunctionalized 6,6''-dimethyl-2,2':6',2''-terpyridines. Using this
      method, hitherto unknown 4,4''-bis(dimethylamino)- and 4,4',4''
      tris(dimethylamino)terpyridines have been prepared that show remarkably high
      calculated Lewis basicities. 

PMID- 24895264
TI  - First patients undergo MRI-guided radiotherapy.

PMID- 24895265
TI  - New tool helps predict risk of prostate cancer overdiagnosis.

PMID- 24895266
TI  - Application of a fast sorting algorithm to the assignment of mass spectrometric
      cross-linking data.
AB  - Cross-linking combined with MS involves enzymatic digestion of cross-linked
      proteins and identifying cross-linked peptides. Assignment of cross-linked
      peptide masses requires a search of all possible binary combinations of peptides
      from the cross-linked proteins' sequences, which becomes impractical with
      increasing complexity of the protein system and/or if digestion enzyme
      specificity is relaxed. Here, we describe the application of a fast sorting
      algorithm to search large sequence databases for cross-linked peptide assignments
      based on mass. This same algorithm has been used previously for assigning
      disulfide-bridged peptides (Choi et al., ), but has not previously been applied
      to cross-linking studies.

PMID- 24895268
TI  - Hypoglycemia from a cardiologist's perspective.
AB  - Hypoglycemia in people with diabetes mellitus (DM) has been potentially linked to
      cardiovascular morbidity and mortality. Pathophysiologically, hypoglycemia
      triggers activation of the sympathoadrenal system, leading to an increase in
      counter-regulatory hormones and, consequently, increased myocardial workload and
      oxygen demand. Additionally, hypoglycemia triggers proinflammatory and
      hematologic changes that provide the substrate for possible myocardial ischemia
      in the already-diseased diabetic cardiovascular system. Hypoglycemia creates
      electrophysiologic alterations causing P-R-interval shortening, ST-segment
      depression, T-wave flattening, reduction of T-wave area, and QTc-interval
      prolongation. Patients who experience hypoglycemia are at an increased risk of
      silent ischemia as well as QTc prolongation and consequent arrhythmias. The
      Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an
      increase in all-cause mortality with intensive glycemic control, whereas the
      Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release
      Controlled Evaluation (ADVANCE) study and Veteran's Affairs Diabetes Trial (VADT)
      showed no benefit with aggressive glycemic control. Women, elderly patients, and
      those with renal insufficiency are more vulnerable to hypoglycemic events. In
      fact, hypoglycemia is the most common metabolic complication experienced by older
      patients with DM in the United States. The concurrent use of medications like
      beta-blockers warrants caution in DM because they can mask warning signs of
      hypoglycemia. Here we aim to elucidate the pathophysiology, review the
      electrocardiographic changes, analyze the current clinical literature, and
      consider the safety considerations of hypoglycemia as it relates to the
      cardiovascular system. In conclusion, in the current era of DM and its vascular
      ramifications, hypoglycemia from a cardiologist's perspective deserves due
      attention. 

PMID- 24895267
TI  - The SHH/Gli pathway is reactivated in reactive glia and drives proliferation in
      response to neurodegeneration-induced lesions.
AB  - In response to neurodegeneration, the adult mammalian brain activates a cellular
      cascade that results in reactive astrogliosis and microgliosis. The mechanism
      through which astrocytes become reactive and the physiological consequences of
      their activation in response to neurodegeneration is complex. While the
      activation and proliferation of astrocytes has been shown to occur during massive
      neuronal cell death, the functional relationship between these two events has not
      been clearly elucidated. Here we show that in response to kainic acid- (KA)
      induced neurodegeneration, the mitogen sonic hedgehog (SHH) is upregulated in
      reactive astrocytes. SHH activity peaks at 7 days and is accompanied by increased
      Gli activity and elevated proliferation in several cell types. To determine the
      functional role of SHH-Gli signaling following KA lesions, we used a
      pharmacological approach to show that SHH secreted by astrocytes drives the
      activation and proliferation of astrocytes and microglia. The consequences of SHH
      Gli signaling in KA-induced lesions appear to be independent of the severity of
      neurodegeneration.

PMID- 24895269
TI  - Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular
      uncoupling, and cognitive decline in mice.
AB  - Epidemiological studies show that obesity has deleterious effects on the brain
      and cognitive function in the elderly population. However, the specific
      mechanisms through which aging and obesity interact to promote cognitive decline
      remain unclear. To test the hypothesis that aging exacerbates obesity-induced
      cerebromicrovascular impairment, we compared young (7 months) and aged (24
      months) high-fat diet-fed obese C57BL/6 mice. We found that aging exacerbates the
      obesity-induced decline in microvascular density both in the hippocampus and in
      the cortex. The extent of hippocampal microvascular rarefaction and the extent of
      impairment of hippocampal-dependent cognitive function positively correlate.
      Aging exacerbates obesity-induced loss of pericyte coverage on cerebral
      microvessels and alters hippocampal angiogenic gene expression signature, which
      likely contributes to microvascular rarefaction. Aging also exacerbates obesity
      induced oxidative stress and induction of NADPH oxidase and impairs cerebral
      blood flow responses to whisker stimulation. Collectively, obesity exerts
      deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular
      rarefaction and neurovascular uncoupling. The morphological and functional
      impairment of the cerebral microvasculature in association with increased blood
      brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et
      al. Obesity in aging exacerbates blood-brain barrier disruption,
      neuroinflammation and oxidative stress in the mouse hippocampus: effects on
      expression of genes involved in beta-amyloid generation and Alzheimer's disease.
      J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to
      obesity-induced cognitive decline in aging. 

PMID- 24895272
TI  - Differential suppression of arousal by sex offenders with intellectual
      disabilities.
AB  - Previous research that has evaluated the ability of sex offenders with
      intellectual disabilities (ID) to suppress sexual arousal has produced mixed
      results. The current study had 2 purposes: (a) to replicate prior research on
      arousal suppression by sex offenders with ID and (b) to evaluate whether it is
      possible for offenders with ID to maintain arousal to nondeviant stimuli while
      suppressing arousal to deviant stimuli. Both participants were successful in
      suppressing arousal to deviant stimuli, and 1 participant was successful in
      maintaining arousal to nondeviant stimuli while suppressing arousal to deviant
      stimuli. 

PMID- 24895270
TI  - GxE interactions between FOXO genotypes and drinking tea are significantly
      associated with prevention of cognitive decline in advanced age in China.
AB  - Logistic regression analysis based on data from 822 Han Chinese oldest old aged
      92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or
      FOXO3-292 and tea drinking at around age 60 or at present time were significantly
      associated with lower risk of cognitive disability at advanced ages. Associations
      between tea drinking and reduced cognitive disability were much stronger among
      carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with
      noncarriers, and it was reconfirmed by analysis of three-way interactions across
      FOXO genotypes, tea drinking at around age 60, and at present time. Based on
      prior findings from animal and human cell models, we postulate that intake of tea
      compounds may activate FOXO gene expression, which in turn may positively affect
      cognitive function in the oldest old population. Our empirical findings imply
      that the health benefits of particular nutritional interventions, including tea
      drinking, may, in part, depend upon individual genetic profiles. 

PMID- 24895271
TI  - Potassium and glucose measures in older adults: the Cardiovascular Health Study.
AB  - BACKGROUND: We sought to determine the impacts of serum and dietary potassium
      measures on glucose metabolism and diabetes risk in older adults. METHODS: Among
      participants of the Cardiovascular Health Study, a community-based cohort of
      older American adults, we examined a) cross-sectional associations between
      potassium and measures of insulin sensitivity and secretion estimated from oral
      glucose tolerance tests and b) longitudinal associations of serum and dietary
      potassium with diabetes risk. RESULTS: Among 4,754 participants aged >=65 years
      at baseline, there were 445 cases of incident diabetes during a median follow-up
      of 12 years. In multivariate models, baseline serum and dietary potassium were
      both associated with lower insulin sensitivity and greater insulin secretion.
      Compared with those with a serum potassium >=4.5 mEq/L, participants with a serum
      potassium <4.0mEq/L had an adjusted mean difference in Matsuda insulin
      sensitivity index of -0.18 (-0.39, 0.02). Compared with those in the highest
      quartile, participants in the lowest quartile of dietary potassium intake had a
      corresponding adjusted mean difference in Matsuda insulin sensitivity index of 
      0.61 (-0.94, -0.29). In multivariate models, neither serum nor dietary potassium
      intake was associated with long-term diabetes risk. CONCLUSIONS: Although we did
      not identify serum and dietary potassium as risk factors for incident diabetes in
      older adults, results from cross-sectional analyses suggest that both may be
      associated with increased insulin resistance. This relationship with insulin
      resistance needs to be confirmed, and its importance on diabetes risk,
      cardiovascular risk, and conditions specific to older adults should be determined
      as well.

PMID- 24895274
TI  - Application of poly 1,8-diaminonaphthalene/multiwalled carbon nanotubes-COOH
      hybrid material as an efficient sorbent for trace determination of cadmium and
      lead ions in water samples.
AB  - Poly 1,8-diaminonaphthalene/multiwalled carbon nanotubes-COOH hybrid material as
      an effective sorbents in solid phase extraction has been developed for the
      separation and preconcentration of Cd(II) and Pb(II) at trace levels in
      environmental water samples. The results indicate that the novel nanocomposite
      show a high affinity for these heavy metals due to the presence of several good
      extractive sites, which are introduced to the synthesized nanocomposite The
      maximum adsorption capacity of the synthesized sorbent for cadmium and lead ions
      was found to be 101.2 and 175.2 mg g(-1) , respectively. The detection limits of
      this method were 0.09 and 0.7 ng ml(-1) for Cd(II) and Pb(II), respectively.

PMID- 24895275
TI  - Ligand-based pharmacophore modelling and screening of DNA minor groove binders
      targeting Staphylococcus aureus.
AB  - The recognition of DNA by small molecules is of special importance in the design
      of new drugs. Many natural and synthetic compounds have the ability to interact
      with the minor groove of DNA. In the present study, identification of minor
      groove binding compounds was attained by the combined approach of pharmacophore
      modelling, virtual screening and molecular dynamics approach. Experimentally
      reported 32 minor groove binding compounds were used to develop the pharmacophore
      model. Based on the fitness score, best three pharmacophore hypotheses were
      selected and used as template for screening the compounds from drug bank
      database. This pharmacophore-based screening provides many compounds with the
      same pharmacological properties. All these compounds were subjected to four
      phases of docking protocols with combined Glide-quantum-polarized ligand docking
      approach. Molecular dynamics results indicated that selected compounds are more
      active and showed good interaction in the binding site of DNA. Based on the
      scoring parameters and energy values, the best compounds were selected, and
      antibacterial activity of these compounds was identified using in vitro
      antimicrobial techniques.

PMID- 24895273
TI  - Nrf2, a regulator of the proteasome, controls self-renewal and pluripotency in
      human embryonic stem cells.
AB  - Nuclear factor, erythroid 2-like 2 (Nrf2) is a master transcription factor for
      cellular defense against endogenous and exogenous stresses by regulating
      expression of many antioxidant and detoxification genes. Here, we show that Nrf2
      acts as a key pluripotency gene and a regulator of proteasome activity in human
      embryonic stem cells (hESCs). Nrf2 expression is highly enriched in hESCs and
      dramatically decreases upon differentiation. Nrf2 inhibition impairs both the
      self-renewal ability of hESCs and re-establishment of pluripotency during
      cellular reprogramming. Nrf2 activation can delay differentiation. During early
      hESC differentiation, Nrf2 closely colocalizes with OCT4 and NANOG. As an
      underlying mechanism, our data show that Nrf2 regulates proteasome activity in
      hESCs partially through proteasome maturation protein (POMP), a proteasome
      chaperone, which in turn controls the proliferation of self-renewing hESCs, three
      germ layer differentiation and cellular reprogramming. Even modest proteasome
      inhibition skews the balance of early differentiation toward mesendoderm at the
      expense of an ectodermal fate by decreasing the protein level of cyclin D1 and
      delaying the degradation of OCT4 and NANOG proteins. Taken together, our findings
      suggest a new potential link between environmental stress and stemness with Nrf2
      and the proteasome coordinately positioned as key mediators.

PMID- 24895276
TI  - Molecular dynamics simulation of the processive endocellulase Cel48F from
      Clostridium cellulolyticum: a novel "water-control mechanism" in enzymatic
      hydrolysis of cellulose.
AB  - Glycoside hydrolase of Cel48F from Clostridium cellulolyticum is an important
      processive cellulose, which can hydrolyze cellulose into cellobiose. Molecular
      dynamics simulations were used to investigate the hydrolysis mechanism of
      cellulose. The two conformations of the Cel48F-cellotetrose complex in which the
      cellotetroses are bound at different sites (known as the sliding conformation and
      the hydrolyzing conformation) were simulated. By comparing these two
      conformations, a water-control mechanism is proposed, in which the hydrolysis
      proceeds by providing a water molecule for every other glucosidic linkage. The
      roles of certain key residues are determined: Glu55 and Asp230 are the most
      probable candidates for acid and base, respectively, in the mechanism of
      inverting anomeric carbon. Met414 and Trp417 constitute the water-control system.
      Glu44 might keep the substrate at a certain location within the active site or
      help the substrate chain to move from the sliding conformation to the hydrolyzing
      conformation. The other hydrophobic residues around the substrate can decrease
      the sliding energy barrier or provide a hydrophobic environment to resist entry
      of the surrounding water molecules into the active site, except for those coming
      from a specific water channel.

PMID- 24895277
TI  - Characterization of molecularly imprinted polymers using a new polar solvent
      titration method.
AB  - A new method of characterizing molecularly imprinted polymers (MIPs) was
      developed and tested, which provides a more accurate means of identifying and
      measuring the molecular imprinting effect. In the new polar solvent titration
      method, a series of imprinted and non-imprinted polymers were prepared in
      solutions containing increasing concentrations of a polar solvent. The polar
      solvent additives systematically disrupted the templation and monomer aggregation
      processes in the prepolymerization solutions, and the extent of disruption was
      captured by the polymerization process. The changes in binding capacity within
      each series of polymers were measured, providing a quantitative assessment of the
      templation and monomer aggregation processes in the imprinted and non-imprinted
      polymers. The new method was tested using three different diphenyl phosphate
      imprinted polymers made using three different urea functional monomers. Each
      monomer had varying efficiencies of templation and monomer aggregation. The new
      MIP characterization method was found to have several advantages. To
      independently verify the new characterization method, the MIPs were also
      characterized using traditional binding isotherm analyses. The two methods
      appeared to give consistent conclusions. First, the polar solvent titration
      method is less susceptible to false positives in identifying the imprinting
      effect. Second, the method is able to differentiate and quantify changes in
      binding capacity, as measured at a fixed guest and polymer concentration, arising
      from templation or monomer aggregation processes in the prepolymerization
      solution. Third, the method was also easy to carry out, taking advantage of the
      ease of preparing MIPs.

PMID- 24895278
TI  - Quantification of interactions among circadian clock proteins via surface plasmon
      resonance.
AB  - Circadian clock is an internal time keeping system recurring 24 h daily rhythm in
      physiology and behavior of organisms. Circadian clock contains transcription and
      translation feedback loop involving CLOCK/NPAS2, BMAL1, Cry1/2, and Per1/2. In
      common, heterodimer of CLOCK/NPAS2 and BMAL1 binds to EBOX element in the
      promoter of Per and Cry genes in order to activate their transcription. CRY and
      PER making heterodimeric complexes enter the nucleus in order to inhibit their
      own BMAL1-CLOCK-activated transcription. The aim of this study was to investigate
      and quantify real-time binding affinities of clock proteins among each other on
      and off DNA modes using surface plasmon resonance. The pairwise interaction
      coefficients among clock proteins, as well as interaction of PER2, CRY2, and PER2
      : CRY2 proteins with BMAL1 : CLOCK complex in the presence and absence of EBOX
      motif have been investigated via analysis of surface plasmon resonance data with
      pseudo first-order reaction kinetics approximation and via nonlinear regression
      curve fitting. The results indicated that CRY2 and PER2, BMAL1, and CLOCK
      proteins form complexes in vitro and that PER2, CRY2 and PER2 : CRY2 complex have
      similar affinities toward BMAL1 : CLOCK complex. CRY2 protein had the highest
      affinity toward EBOX complex, whereas PER2 and CRY2 : PER2 complexes displayed
      low affinity toward EBOX complex. The quantification of the interaction between
      clock proteins is critical to understand the operation mechanism of the
      biological clock and to address the behavioral and physiological disorders, and
      it will be useful for the design of new drugs toward clock-related diseases.

PMID- 24895280
TI  - A cooperative N-heterocyclic carbene/chiral phosphate catalysis system for
      allenolate annulations.
AB  - The highly enantioselective NHC-catalyzed [3+2] annulation reaction with
      alpha,beta-alkynals and alpha-ketoesters has been developed. A new mode of
      cooperative catalysis involving the combination of a chiral Bronsted acid and a
      C1-symmetric biaryl saturated-imidazolium precatalyst was required to generate
      the desired gamma-crotonolactones in high yields and levels of
      enantioselectivity.

PMID- 24895281
TI  - Extranuclear estrogen receptor's roles in physiology: lessons from mouse models.
AB  - Steroid receptors exist and function in multiple compartments of cells in most
      organs. Although the functions and nature of some of these receptors is being
      defined, important aspects of receptor localization and signaling to physiology
      and pathophysiology have been identified. In particular, extranuclear sex steroid
      receptors have been found in many normal cells and in epithelial tumors, where
      they enact signal transduction that impacts both nongenomic and genomic
      functions. Here, I focus on the progress made in understanding the roles of
      extranuclear estrogen receptors (ER) in physiology and pathophysiology.
      Extranuclear ER serve as a model to selectively intervene with novel receptor
      reagents to prevent or limit disease progression. Recent novel mouse models and
      membrane ER-selective agonists also provide a better understanding of receptor
      pool cross-talk that results in the overall integrative actions of sex steroids. 

PMID- 24895283
TI  - Distinct mechanisms of induction of hepatic growth hormone resistance by
      endogenous IL-6, TNF-alpha, and IL-1beta.
AB  - During inflammation, the liver becomes resistant to growth hormone (GH) actions,
      leading to downregulation of the GH target gene IGF-I and activation of
      catabolism. Proinflammatory cytokines IL-6, TNF-alpha, and IL-1beta are
      critically involved in the pathogenesis of hepatic GH resistance. However, the
      mechanisms used by endogenous IL-6, TNF-alpha, and IL-1beta to inhibit the
      hepatic GH-IGF-I pathway during inflammation are not fully understood. Here, we
      show that TNF-alpha and IL-1beta inhibited GH receptor (GHR) expression but had
      minor effects on the downstream suppressor of cytokine signaling (SOCS)3, while
      IL-6 induced SOCS3 expression but had no effect on GHR expression in Huh-7 cells.
      Consistent with the in vitro observations, neutralization of TNF-alpha and IL
      1beta in mouse models of inflammation did not significantly alter SOCS3
      expression stimulated by inflammation but restored GHR and IGF-I expression
      suppressed by inflammation. Neutralization of IL-6 did not alter inflammation
      suppressed GHR expression but drastically reduced the inflammation-stimulated
      SOCS3 expression and restored IGF-I expression. Interestingly, when the GH-IGF-I
      pathway was turned off by maximal inhibition of GHR expression, IL-6 and SOCS3
      were no longer able to regulate IGF-I expression. Taken together, our results
      suggest that TNF-alpha/IL-1beta and IL-6 use distinct mechanisms to induce
      hepatic GH resistance, with TNF-alpha and IL-1beta acting primarily on GHR and IL
      6 acting primarily on SOCS3. IL-6 action may be superseded by factors such as TNF
      alpha and IL-1beta that inhibit GHR expression. 

PMID- 24895282
TI  - p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy
      during limb immobilization.
AB  - Immobilization causes skeletal muscle atrophy via complex signaling pathways that
      are not well understood. To better understand these pathways, we investigated the
      roles of p53 and ATF4, two transcription factors that mediate adaptations to a
      variety of cellular stresses. Using mouse models, we demonstrate that 3 days of
      muscle immobilization induces muscle atrophy and increases expression of p53 and
      ATF4. Furthermore, muscle fibers lacking p53 or ATF4 are partially resistant to
      immobilization-induced muscle atrophy, and forced expression of p53 or ATF4
      induces muscle fiber atrophy in the absence of immobilization. Importantly,
      however, p53 and ATF4 do not require each other to promote atrophy, and
      coexpression of p53 and ATF4 induces more atrophy than either transcription
      factor alone. Moreover, muscle fibers lacking both p53 and ATF4 are more
      resistant to immobilization-induced atrophy than fibers lacking only p53 or ATF4.
      Interestingly, the independent and additive nature of the p53 and ATF4 pathways
      allows for combinatorial control of at least one downstream effector, p21. Using
      genome-wide mRNA expression arrays, we identified p21 mRNA as a skeletal muscle
      transcript that is highly induced in immobilized muscle via the combined actions
      of p53 and ATF4. Additionally, in mouse muscle, p21 induces atrophy in a manner
      that does not require immobilization, p53 or ATF4, and p21 is required for
      atrophy induced by immobilization, p53, and ATF4. Collectively, these results
      identify p53 and ATF4 as essential and complementary mediators of immobilization
      induced muscle atrophy and discover p21 as a critical downstream effector of the
      p53 and ATF4 pathways. 

PMID- 24895285
TI  - Kinetics and utilization of lipid sources during acute exercise and acipimox.
AB  - Overweight is associated with abnormalities of lipid metabolism, many of which
      are reversed by exercise. We investigated the impact of experimental
      antilipolysis and acute exercise on lipid kinetics and oxidation from VLDL-TG,
      plasma FFA, and "residual lipids" in overweight men (n = 8) using VLDL-TG and
      palmitate tracers in combination with muscle biopsies in a randomized, placebo
      controlled design. Participants received placebo or acipimox on each study day (4
      h of rest, 90 min of exercise at 50% V(O(2 max))). Exercise suppressed VLDL-TG
      secretion significantly during placebo but not acipimox (placebo-rest: 64.2 +/-
      9.4; placebo-exercise: 48.3 +/- 8.0; acipimox-rest: 55.2 +/- 13.4; acipimox
      exercise: 52.0 +/- 10.9). Resting oxidation of VLDL-TG FA and FFA was
      significantly reduced during acipimox compared with placebo, whereas "residual
      lipid oxidation" increased significantly [VLDL-TG oxidation (placebo: 18 +/- 3
      kcal/h; acipimox: 11 +/- 2 kcal/h), FFA oxidation (placebo: 14 +/- 2 kcal/h;
      acipimox: 4 +/- 0.5 kcal/h), and residual lipid oxidation (placebo: 3 +/- 5
      kcal/h; acipimox: 14 +/- 5 kcal/h)]. Additionally, during exercise on both
      placebo and acipimox, oxidation of VLDL-TG and FFA increased, but the relative
      contribution to total lipid oxidation diminished, except for FFA, which remained
      unchanged during acipimox. Residual lipid oxidation increased significantly
      during exercise in both absolute and relative terms. Changes in selected cellular
      enzymes and proteins provided no explanations for kinetic changes. In conclusion,
      suppressed FFA availability blunts the effect of exercise on VLDL-TG secretion
      and modifies the contribution of lipid sources for oxidation.

PMID- 24895284
TI  - Ca2+ signals promote GLUT4 exocytosis and reduce its endocytosis in muscle cells.
AB  - Elevating cytosolic Ca(2+) stimulates glucose uptake in skeletal muscle, but how
      Ca(2+) affects intracellular traffic of GLUT4 is unknown. In tissue, changes in
      Ca(2+) leading to contraction preclude analysis of the impact of individual,
      Ca(2+)-derived signals. In L6 muscle cells stably expressing GLUT4myc, the Ca(2+)
      ionophore ionomycin raised cytosolic Ca(2+) and caused a gain in cell surface
      GLUT4myc. Extra- and intracellular Ca(2+) chelators (EGTA, BAPTA-AM) reversed
      this response. Ionomycin activated calcium calmodulin kinase II (CaMKII), AMPK,
      and PKCs, but not Akt. Silencing CaMKIIdelta or AMPKalpha1/alpha2 partly reduced
      the ionomycin-induced gain in surface GLUT4myc, as did peptidic or small molecule
      inhibitors of CaMKII (CN21) and AMPK (Compound C). Compared with the conventional
      isoenzyme PKC inhibitor Go6976, the conventional plus novel PKC inhibitor Go6983
      lowered the ionomycin-induced gain in cell surface GLUT4myc. Ionomycin stimulated
      GLUT4myc exocytosis and inhibited its endocytosis in live cells. siRNA-mediated
      knockdown of CaMKIIdelta or AMPKalpha1/alpha2 partly reversed ionomycin-induced
      GLUT4myc exocytosis but did not prevent its reduced endocytosis. Compared with
      Go6976, Go6983 markedly reversed the slowing of GLUT4myc endocytosis triggered by
      ionomycin. In summary, rapid Ca(2+) influx into muscle cells accelerates GLUT4myc
      exocytosis while slowing GLUT4myc endocytosis. CaMKIIdelta and AMPK stimulate
      GLUT4myc exocytosis, whereas novel PKCs reduce endocytosis. These results
      identify how Ca(2+)-activated signals selectively regulate GLUT4 exocytosis and
      endocytosis in muscle cells. 

PMID- 24895286
TI  - Calcium signaling recruits substrate transporters GLUT4 and CD36 to the
      sarcolemma without increasing cardiac substrate uptake.
AB  - Activation of AMP-activated protein kinase (AMPK) in cardiomyocytes induces
      translocation of glucose transporter GLUT4 and long-chain fatty acid (LCFA)
      transporter CD36 from endosomal stores to the sarcolemma to enhance glucose and
      LCFA uptake, respectively. Ca(2+)/calmodulin-activated kinase kinase-beta
      (CaMKKbeta) has been positioned directly upstream of AMPK. However, it is unknown
      whether acute increases in [Ca(2+)]i stimulate translocation of GLUT4 and CD36
      and uptake of glucose and LCFA or whether Ca(2+) signaling converges with AMPK
      signaling to exert these actions. Therefore, we studied the interplay between
      Ca(2+) and AMPK signaling in regulation of cardiomyocyte substrate uptake.
      Exposure of primary cardiomyocytes to inhibitors or activators of Ca(2+)
      signaling affected neither AMPK-Thr(172) phosphorylation nor basal and AMPK
      mediated glucose and LCFA uptake. Despite their lack of an effect on substrate
      uptake, Ca(2+) signaling activators induced GLUT4 and CD36 translocation. In
      contrast, AMPK activators stimulated GLUT4/CD36 translocation as well as
      glucose/LCFA uptake. When cardiomyocytes were cotreated with Ca(2+) signaling and
      AMPK activators, Ca(2+) signaling activators further enhanced AMPK-induced
      glucose/LCFA uptake. In conclusion, Ca(2+) signaling shows no involvement in AMPK
      induced GLUT4/CD36 translocation and substrate uptake but elicits transporter
      translocation via a separate pathway requiring CaMKKbeta/CaMKs. Ca(2+)-induced
      transporter translocation by itself appears to be ineffective to increase
      substrate uptake but requires additional AMPK activation to effectuate
      transporter translocation into increased substrate uptake. Ca(2+)-induced
      transporter translocation might be crucial under excessive cardiac stress
      conditions that require supraphysiological energy demands. Alternatively, Ca(2+)
      signaling might prepare the heart for substrate uptake during physiological
      contraction by inducing transporter translocation. 

PMID- 24895288
TI  - Tolvaptan in hospitalized cancer patients with hyponatremia: a double-blind,
      randomized, placebo-controlled clinical trial on efficacy and safety.
AB  - BACKGROUND: The rate of hyponatremia is higher in hospitalized cancer patients
      than in hospitalized patients without cancer and is associated with poor clinical
      outcomes. The availability of V2 receptor antagonists has been a major
      breakthrough in the management of hyponatremia, but its efficacy and safety in
      treating hyponatremia in patients with cancer is not known. METHODS: Adult
      patients with cancer who were admitted to The University of Texas MD Anderson
      Cancer Center with nonhypovolemic hyponatremia (125-130 mmol/L) were randomized
      to receive either tolvaptan or placebo in a double-blind, placebo-controlled,
      adaptive, randomized trial. Both groups received the standard of care for
      hyponatremia, except that patients were allowed to drink to thirst. RESULTS: A
      preplanned Data Safety Monitoring Board analysis of 30 of 48 randomized patients
      who completed the study revealed that the primary endpoint of hyponatremia
      correction was met by 16 of 17 patients who received tolvaptan and by 1 of 13
      patients who received placebo (94% vs 8%; P < .001), which met the study stopping
      rule for superiority. The secondary endpoints between the tolvaptan and placebo
      groups (mean +/- standard deviation) for length of stay (21 +/- 15 days vs 26 +/-
      15 days, respectively) and change in the Mini-Mental State Examination score (
      0.35 +/- 1.66 vs 0.31 +/- 2.42, respectively) were not significantly different.
      No overcorrection of serum sodium (>12 mmol/L per day) was noted in the tolvaptan
      group, and the main adverse events noted were dry mouth, polydipsia, and
      polyuria, leading to 13% study withdrawal. CONCLUSIONS: Although tolvaptan was
      effective for correcting hyponatremia in patients with cancer, studies with a
      larger sample size will be required to confirm the current findings, including
      the outcomes of secondary endpoints.

PMID- 24895287
TI  - Managing body image difficulties of adult cancer patients: lessons from available
      research.
AB  - BACKGROUND: Body image is a critical psychosocial issue for patients with cancer
      because they often undergo significant changes to appearance and functioning. The
      primary purpose of this review article was to identify empirically-supported
      approaches to treat body image difficulties of adult cancer patients that can be
      incorporated into high-quality comprehensive cancer care. METHODS: An overview
      was provided of theoretical models of body image relevant to cancer patients, and
      findings were presented from published literature on body image and cancer from
      2003 to 2013. These data were integrated with information from the patient-doctor
      communication literature to delineate a practical approach for assessing and
      treating body image concerns of adult cancer patients. RESULTS: Body image
      difficulties were found across patients with diverse cancer sites, and were most
      prevalent in the immediate postoperative and treatment period. Age, body mass
      index, and specific cancer treatments have been identified as potential risk
      factors for body image disturbance in cancer patients. Current evidence supports
      the use of time-limited cognitive-behavioral therapy interventions for addressing
      these difficulties. Other intervention strategies also show promise but require
      further study. Potential indicators of body image difficulties were identified to
      alert health care professionals when to refer patients for psychosocial care, and
      a framework was proposed for approaching conversations about body image that can
      be used by the oncologic treatment team. CONCLUSIONS: Body image issues affect a
      wide array of cancer patients. Providers can use available evidence combined with
      information from the health care communication literature to develop practical
      strategies for treating body image concerns of patients with cancer.

PMID- 24895289
TI  - Chitosan microsphere scaffold tethered with RGD-conjugated poly(methacrylic acid)
      brushes as effective carriers for the endothelial cells.
AB  - Endothelial cell-matrix interactions play a vital role in promoting
      vascularization of engineered tissues. The current study reports a facile and
      controllable method to develop a RGD peptide-functionalized chitosan microsphere
      scaffolds for rapid cell expansion of human umbilical vein endothelial cells
      (HUVECs). Functional poly(methacrylic acid) (PMAA) brushes are grafted from the
      chitosan microsphere surfaces via surface-initiated ATRP. Subsequent conjugation
      of RGD peptides on the pendent carboxyl groups of PMAA side chain is accomplished
      by carbodiimide chemistry to facilitate biocompatibility of the 3D CS scaffolding
      system. In vitro cell-loading assay of HUVECs exhibits a significant improvment
      of cell adhesion, spreading, and proliferation on the RGD peptide-immobilized CS
      microsphere surfaces. 

PMID- 24895291
TI  - Primary malignancies of the heart and pericardium.
AB  - Primary malignancies of the heart and pericardium are rare. All the available
      data come from autopsy studies, case reports, and, in recent years, from large,
      specialized, single-center studies. Nevertheless, if primary malignancy is
      present, it may have a devastating implication for patients. Malignancies may
      affect heart function, also causing left-sided or right-sided heart failure. In
      addition, they can be responsible for embolic events or arrhythmias. Today, with
      the widespread use of noninvasive imaging modalities, heart tumors become
      evident, even as an incidental finding. A multimodality imaging approach is
      usually required to establish the final diagnosis. Despite the increased
      awareness and improved diagnostic techniques, clinical manifestations of primary
      malignancy of the heart and pericardium are so variable that their occurrence may
      still come as a surprise during surgery or autopsy. No randomized clinical trials
      have been carried out to determine the optimal therapy for these primary
      malignancies. Surgery is performed for small tumors. Chemotherapy and radiation
      therapy can be of help. Partial resection of large neoplasms is performed to
      relieve mechanical effects, such as cardiac compression or hemodynamic
      obstruction. Most patients present with marginally resectable or technically
      nonresectable disease at the time of diagnosis. It seems that orthotopic cardiac
      transplantation with subsequent immunosuppressive therapy may represent an option
      for very carefully selected patients. Early diagnosis and radical exeresis are of
      great importance for long-term survival of a primary cardiac malignancy. This can
      rarely be accomplished, and overall results are very disappointing. 

PMID- 24895290
TI  - Astrocyte-neuron interaction in the substantia gelatinosa of the spinal cord
      dorsal horn via P2X7 receptor-mediated release of glutamate and reactive oxygen
      species.
AB  - The substantia gelatinosa (SG) of the spinal cord processes incoming painful
      information to ascending projection neurons. Whole-cell patch clamp recordings
      from SG spinal cord slices documented that in a low Ca(2+) /no Mg(2+) (low X(2+)
      ) external medium adenosine triphosphate (ATP)/dibenzoyl-ATP, Bz-ATP) caused
      inward current responses, much larger in amplitude than those recorded in a
      normal X(2+) -containing bath medium. The effect of Bz-ATP was antagonized by the
      selective P2X7 receptor antagonist A-438079. Neuronal, but not astrocytic Bz-ATP
      currents were strongly inhibited by a combination of the ionotropic glutamate
      receptor antagonists AP-5 and CNQX. In fact, all neurons and some astrocytes
      responded to NMDA, AMPA, and muscimol with inward current, demonstrating the
      presence of the respective receptors. The reactive oxygen species H2 O2
      potentiated the effect of Bz-ATP at neurons but not at astrocytes. Hippocampal
      CA1 neurons exhibited a behavior similar to, but not identical with SG neurons.
      Although a combination of AP-5 and CNQX almost abolished the effect of Bz-ATP, H2
      O2 was inactive. A Bz-ATP-dependent and A-438079-antagonizable reactive oxygen
      species production in SG slices was proven by a microelectrode biosensor.
      Immunohistochemical investigations showed the colocalization of P2X7
      immunoreactivity with microglial (Iba1), but not astrocytic (GFAP, S100beta) or
      neuronal (MAP2) markers in the SG. It is concluded that SG astrocytes possess
      P2X7 receptors; their activation leads to the release of glutamate, which via
      NMDA- and AMPA receptor stimulation induces cationic current in the neighboring
      neurons. P2X7 receptors have a very low density under resting conditions but
      become functionally upregulated under pathological conditions.

PMID- 24895292
TI  - Youth exposure to e-cigarette advertising on US television soars.

PMID- 24895293
TI  - Biogenesis of D-amino acid containing peptides/proteins: where, when and how?
AB  - Peptides and proteins are chiral molecules with their structure determined by the
      composition and configuration of the amino acids constituting them. Natural amino
      acids (except glycine) display two chiral types (l- and d-enantiomers). For
      example, the presence of octopine, a derivative of l-arginine and d-alanine in
      octopus, or peptidyl poly-d-glutamic acid in a bacterial cell wall was
      demonstrated in the 1920s and 1930s, respectively. Nevertheless, an old dogma in
      biology was that proteins (in a strict sense) are composed of amino acids in the
      l-configuration exclusively, until a d-alanyl residue was reported in a frog skin
      opioid peptide in the early 1980s, and since, numerous d-amino acid containing
      peptides (DAACPs) have been discovered in multicellular organisms. Several
      hypotheses may be formulated to explain the origin of a d-residue in the
      peptide/protein chain. It may result from different mechanisms such as
      incorporation of a d-amino acid, non-enzymatic racemisation associated with
      ageing or diseases and enzymatic posttranslational modification. In the last
      case, the DAACPs are synthesised via a ribosome-dependent manner, and a normal
      codon for l-amino acid is present in the mRNA at the position where the d-residue
      is processed in the mature peptide by peptidyl aminoacyl l-d isomerisation, a
      peculiar and subtle posttranslational modification. In this review, the different
      pathways of biogenesis of DAACPs not only in bacteria but also in multicellular
      organisms are discussed, along with the description of the cellular specificity,
      the enzyme specificity and the substrate specificity of peptidyl aminoacyl l-d
      isomerisation.

PMID- 24895294
TI  - Validation of the use of radiographic fracture-healing scores in a small animal
      model.
AB  - Precise assessment of fracture-healing is vital in both clinical and research
      settings, where therapies are typically assessed using animal models with union
      as the study end point. Radiographic scoring systems have been developed for
      clinical use; however have not been validated in pre-clinical models. Thirty sets
      of radiographs of rat tibial shaft fractures, treated with external fixation were
      reviewed by six observers using the Radiographic Union in Tibia (RUST) scale, the
      Lane & Sandhu score, and an overall impression of union. Fleiss's kappa and Intra
      class Correlation Coefficients (ICC) were used to determine reliability. Inter
      observer and intra-observer agreement using the general impression score were
      moderate [kappa; 0.58; 95%CI (0.49-0.65) and 0.66 (0.43-0.89), respectively].
      Inter-observer and intra-observer agreement were excellent using both the RUST
      score [ICC; 0.81 (0.72-0.89) and 0.86 (0.74-0.93), respectively], and Lane &
      Sandhu score [ICC; 0.88 (0.81-0.93) and 0.90 (0.81-0.95), respectively].
      Employing a defined scoring system enhances both the reproducibility and
      repeatability of bone healing assessment in a small animal model. Routine
      reporting of fracture scoring methodology should be encouraged to enrich results
      and facilitate data synthesis across studies.

PMID- 24895295
TI  - ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT)
      on prenatal ultrasound practice.

PMID- 24895297
TI  - Developing Exon-Primed Intron-Crossing (EPIC) markers for population genetic
      studies in three Aedes disease vectors.
AB  - Aedes aegypti, Aedes notoscriptus, and Aedes albopictus are important vectors of
      many arboviruses implicated in human disease such as dengue fever. Genetic
      markers applied across vector species can provide important information on
      population structure, gene flow, insecticide resistance, and taxonomy, however,
      robust microsatellite markers have proven difficult to develop in these species
      and mosquitoes generally. Here we consider the utility and transferability of 15
      Ribosome protein (Rp) Exon-Primed Intron-Crossing (EPIC) markers for population
      genetic studies in these 3 Aedes species. Rp EPIC markers designed for Ae.
      aegypti also successfully amplified populations of the sister species, Ae.
      albopictus, as well as the distantly related species, Ae. notoscriptus. High SNP
      and good indel diversity in sequenced alleles plus support for amplification of
      the same regions across populations and species were additional benefits of these
      markers. These findings point to the general value of EPIC markers in mosquito
      population studies. 

PMID- 24895298
TI  - Functionalization of a cyclo-P5 ligand by main-group element nucleophiles.
AB  - Unprecedented functionalized products with an eta(4)-P5 ring are obtained by the
      reaction of [Cp*Fe(eta(5)-P5)] (1; Cp*=eta(5)-C5Me5) with different nucleophiles.
      With LiCH2SiMe3 and LiNMe2, the monoanionic products [Cp*Fe(eta(4)-P5CH2SiMe3)](
      ) and [Cp*Fe(eta(4)-P5NMe2)](-), respectively, are formed. The reaction of 1 with
      NaNH2 leads to the formation of the trianionic compound [{Cp*Fe(eta(4)-P5)}2N](3
      ), whereas the reaction with LiPH2 yields [Cp*Fe(eta(4)-P5PH2)](-) as the main
      product, with {[Cp*Fe(eta(4)-P5)]2PH}(2-) as a byproduct. The calculated energy
      profile of the reactions provides a rationale for the formation of the different
      products.

PMID- 24895296
TI  - Generation of mice carrying a knockout-first and conditional-ready allele of
      transforming growth factor beta2 gene.
AB  - Transforming growth factor beta2 (TGFbeta2) is a multifunctional protein which is
      expressed in several embryonic and adult organs. TGFB2 mutations can cause Loeys
      Dietz syndrome, and its dysregulation is involved in cardiovascular, skeletal,
      ocular, and neuromuscular diseases, osteoarthritis, tissue fibrosis, and various
      forms of cancer. TGFbeta2 is involved in cell growth, apoptosis, cell migration,
      cell differentiation, cell-matrix remodeling, epithelial-mesenchymal transition,
      and wound healing in a highly context-dependent and tissue-specific manner.
      Tgfb2(-/-) mice die perinatally from congenital heart disease, precluding
      functional studies in adults. Here, we have generated mice harboring
      Tgfb2(betageo) (knockout-first lacZ-tagged insertion) gene-trap allele and
      Tgfb2(flox) conditional allele. Tgfb2(betageo/betageo) or Tgfb2(betageo/-) mice
      died at perinatal stage from the same congenital heart defects as Tgfb2(-/-)
      mice. beta-galactosidase staining successfully detected Tgfb2 expression in the
      heterozygous Tgfb2(betageo) fetal tissue sections. Tgfb2(flox) mice were produced
      by crossing the Tgfb2(+/betageo) mice with the FLPeR mice. Tgfb2(flox/-) mice
      were viable. Tgfb2 conditional knockout (Tgfb2(cko/-) ) fetuses were generated by
      crossing of Tgfb2(flox/-) mice with Tgfb2(+/-) ; EIIaCre mice. Systemic
      Tgfb2(cko/-) embryos developed cardiac defects which resembled the
      Tgfb2(betageo/betageo) , Tgfb2(betageo/-) , and Tgfb2(-/-) fetuses. In
      conclusion, Tgfb2(betageo) and Tgfb2(flox) mice are novel mouse strains which
      will be useful for investigating the tissue specific expression and function of
      TGFbeta2 in embryonic development, adult organs, and disease pathogenesis and
      cancer. genesis

PMID- 24895299
TI  - Aloe vera for prevention and treatment of infusion phlebitis.
AB  - BACKGROUND: Up to 80% of hospitalised patients receive intravenous therapy at
      some point during their admission. About 20% to 70% of patients receiving
      intravenous therapy develop phlebitis. Infusion phlebitis has become one of the
      most common complications in patients with intravenous therapy. However, the
      effects of routine treatments such as external application of 75% alcohol or 50%
      to 75% magnesium sulphate (MgSO4) are unsatisfactory. Therefore, there is an
      urgent need to develop new methods to prevent and alleviate infusion phlebitis.
      OBJECTIVES: To systematically assess the effects of external application of Aloe
      vera for the prevention and treatment of infusion phlebitis associated with the
      presence of an intravenous access device. SEARCH METHODS: The Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised
      Register (last searched February 2014) and CENTRAL (2014, Issue 1). In addition
      the TSC searched MEDLINE to week 5 January 2014, EMBASE to Week 6 2014 and AMED
      to February 2014. The authors searched the following Chinese databases until 28
      February 2014: Chinese BioMedical Database; Traditional Chinese Medical Database
      System; China National Knowledge Infrastructure; Chinese VIP information; Chinese
      Medical Current Contents; Chinese Academic Conference Papers Database and Chinese
      Dissertation Database; and China Medical Academic Conference. Bibliographies of
      retrieved and relevant publications were searched. There were no restrictions on
      the basis of date or language of publication. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) and quasi-randomised controlled trials (qRCTs) were
      included if they involved participants receiving topical Aloe vera or Aloe vera
      derived products at the site of punctured skin, with or without routine treatment
      at the same site. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted the data on the study characteristics, description of methodology and
      outcomes of the eligible trials, and assessed study quality. Data were analysed
      using RevMan 5.1. For dichotomous outcomes, the effects were estimated by using
      risk ratio (RR) with its 95% confidence interval (CI). For continuous outcomes,
      mean differences (MD) with 95% CIs were used to estimate their effects. MAIN
      RESULTS: A total of 43 trials (35 RCTs and eight qRCTs) with 7465 participants
      were identified. Twenty-two trials with 5546 participants were involved in
      prevention of Aloe vera for phlebitis, and a further 21 trials with 1919
      participants were involved in the treatment of phlebitis. The included studies
      compared external application of Aloe vera alone or plus non-Aloe vera
      interventions with no treatment or the same non-Aloe vera interventions. The
      duration of the intervention lasted from one day to 15 days. Most of the included
      studies were of low methodological quality with concerns for selection bias,
      attrition bias, reporting bias and publication bias.The effects of external
      application of fresh Aloe vera on preventing total incidence of phlebitis varied
      across the studies and we did not combine the data. Aloe vera reduced the
      occurrence of third degree phlebitis (RR 0.06, 95% CI 0.03 to 0.11, P < 0.00001)
      and second degree phlebitis (RR 0.18, 95% CI 0.10 to 0.31, P < 0.00001) compared
      with no treatment. Compared with external application of 75% alcohol, or 33%
      MgSO4 alone, Aloe vera reduced the total incidence of phlebitis (RR 0.02, 95% CI
      0.00 to 0.28, P = 0.004 and RR 0.43, 95% CI 0.24 to 0.78, P = 0.005 respectively)
      but there was no clear evidence of an effect when compared with 50% or 75% MgSO4
      (total incidence of phlebitis RR 0.41, 95% CI 0.16 to 1.07, P = 0.07 and RR 1.10
      95% CI 0.54 to 2.25, P = 0.79 respectively; third degree phlebitis (RR 0.28, 95%
      CI 0.07 to 1.02, P = 0.051 and RR 1.19, 95% CI 0.08 to 18.73, P = 0.9
      respectively; second degree phlebitis RR 0.68, 95% CI 0.21 to 2.23, P = 0.53
      compared to 75% MgSO4) except for a reduction in second degree phlebitis when
      Aloe vera was compared with 50% MgSO4 (RR 0.26, 95% CI 0.14 to 0.50, P <
      0.0001).For the treatment of phlebitis, Aloe vera was more effective than 33% or
      50% MgSO4 in terms of both any improvement (RR 1.16, 95% CI 1.09 to 1.24, P <
      0.0001 and RR 1.22, 95% CI 1.16 to 1.28, P < 0.0001 respectively) and marked
      improvement of phlebitis (RR 1.97, 95% CI 1.44 to 2.70, P < 0.001 and RR 1.56,
      95% CI 1.29 to 1.87, P = 0.0002 respectively). Compared with 50% MgSO4, Aloe vera
      also improved recovery rates from phlebitis (RR 1.42, 95% CI 1.24 to 1.61, P <
      0.0001). Compared with routine treatments such as external application of
      hirudoid, sulphonic acid mucopolysaccharide and dexamethasone used alone,
      addition of Aloe vera improved recovery from phlebitis (RR 1.75, 95% CI 1.24 to
      2.46, P = 0.001) and had a positive effect on overall improvement (marked
      improvement RR 1.26, 95% CI 1.09 to 1.47, P = 0.0003; any improvement RR 1.23,
      95% CI 1.13 to 1.35, P < 0.0001). Aloe vera, either alone or in combination with
      routine treatment, was more effective than routine treatment alone for improving
      the symptoms of phlebitis including shortening the time of elimination of red
      swelling symptoms, time of pain relief at the location of the infusion vein and
      time of resolution of phlebitis. Other secondary outcomes including health
      related quality of life and adverse effects were not reported in the included
      studies. AUTHORS' CONCLUSIONS: There is no strong evidence for preventing or
      treating infusion phlebitis with external application of Aloe vera. The current
      available evidence is limited by the poor methodological quality and risk of
      selective outcome reporting of the included studies, and by variation in the size
      of effect across the studies. The positive effects observed with external
      application of Aloe vera in preventing or treating infusion phlebitis compared
      with no intervention or external application of 33% or 50% MgSO4 should therefore
      be viewed with caution.

PMID- 24895300
TI  - On the effect of setting of a positive surgical margin in soft tissue sarcoma.

PMID- 24895302
TI  - "A greater misfortune can scarcely be imagined...".

PMID- 24895301
TI  - A randomized, split-face clinical trial of low-fluence Q-switched neodymium-doped
      yttrium aluminum garnet (1,064 nm) laser versus low-fluence Q-switched
      alexandrite laser (755 nm) for the treatment of facial melasma.
AB  - BACKGROUND: Melasma is distressing for patients and challenging for physicians to
      treat. Clinical data from controlled comparative studies is lacking to support
      the efficacy, longevity, and safety of laser treatments for melasma. OBJECTIVE:
      Compare the efficacy and safety of low fluence Q-switched neodymium-doped yttrium
      aluminum garnet (1,064 nm) laser (Nd:YAG) versus low-fluence Q-switched
      alexandrite laser (755 nm) (QSAL) for the treatment of facial melasma. METHODS:
      Twenty male and female subjects with moderate to severe mixed-type melasma on
      both sides of the face were randomized to six, weekly treatments with the low
      fluence Q-switched Nd:YAG laser on one side and the low-fluence QSAL to the other
      side. Two independent investigators conducted Modified Melasma Area and Severity
      Index (MMASI) evaluations and subjects completed self-assessment questionnaires
      at baseline, after three treatments and each follow-up visit 2, 12, and 24 weeks
      after the last treatment. Standardized digital photographs were taken at baseline
      and at each subsequent follow-up visit. RESULTS: One male and fifteen females,
      mean age of 43.4 (range 32-64) years, completed the 29-week study. Both laser
      treated sides showed a significant improvement in MMASI evaluations after two
      treatments (22% improvement on the QS-Nd:YAG, 17% QSAL) and each follow-up visit
      2 (36% QS-Nd:YAG; 44% QSAL), 12 (27% QS-Nd:YAG; and 24% QSAL), and 24 weeks (27%
      QS-Nd:YAG; and 19% QSAL) after the last treatment, but no significant difference
      was seen between study groups at any visit. There was also no significant
      difference in subject evaluation of improvement between both treatment sides at
      any visit. Both laser treated sides were tolerated well, and no serious adverse
      events were noted. Only one subject was taken out of the study due to development
      of post-inflammatory hyperpigmentation bilaterally. CONCLUSION: Both low-fluence
      Q-switched Nd:YAG and low-fluence QSAL were equally effective at improving
      moderate to severe mixed-type facial melasma. LIMITATIONS: This was a single
      center trial and patients were not able to use complimentary lightening agents
      during the study.

PMID- 24895303
TI  - An Asian origin of virulent Aeromonas hydrophila responsible for disease
      epidemics in United States-farmed catfish.
AB  - Since 2009, catfish farming in the southeastern United States has been severely
      impacted by a highly virulent and clonal population of Aeromonas hydrophila
      causing motile Aeromonas septicemia (MAS) in catfish. The possible origin of this
      newly emerged highly virulent A. hydrophila strain is unknown. In this study, we
      show using whole-genome sequencing and comparative genomics that A. hydrophila
      isolates from diseased grass carp in China and catfish in the United States have
      highly similar genomes. Our phylogenomic analyses suggest that U.S. catfish
      isolates emerged from A. hydrophila populations of Asian origin. Furthermore, we
      identified an A. hydrophila strain isolated in 2004 from a diseased catfish in
      Mississippi, prior to the onset of the major epidemic outbreaks in Alabama
      starting in 2009, with genomic characteristics that are intermediate between
      those of the Asian and Alabama fish isolates. Investigation of A. hydrophila
      strain virulence demonstrated that the isolate from the U.S. catfish epidemic is
      significantly more virulent to both channel catfish and grass carp than is the
      Chinese carp isolate. This study implicates the importation of fish or fishery
      products into the United States as the source of highly virulent A. hydrophila
      that has caused severe epidemic outbreaks in United States-farmed catfish and
      further demonstrates the potential for invasive animal species to disseminate
      bacterial pathogens worldwide. IMPORTANCE: Catfish aquaculture farming in the
      southeastern United States has been severely affected by the emergence of
      virulent Aeromonas hydrophila responsible for epidemic disease outbreaks,
      resulting in the death of over 10 million pounds of catfish. Because the origin
      of this newly emerged A. hydrophila strain is unknown, this study used a
      comparative genomics approach to conduct a phylogenomic analysis of A. hydrophila
      isolates obtained from the United States and Asia. Our results suggest that the
      virulent isolates from United States-farmed catfish have a recent common ancestor
      with A. hydrophila isolates from diseased Asian carp. We have also observed that
      an Asian carp isolate, like recent U.S. catfish isolates, is virulent in catfish.
      The results from this study suggest that the highly virulent U.S. epidemic
      isolates emerged from an Asian source and provide another example of the threat
      that invasive species pose in the dissemination of bacterial pathogens.

PMID- 24895304
TI  - Invasion of the central nervous system by Cryptococcus neoformans requires a
      secreted fungal metalloprotease.
AB  - Cryptococcus spp. cause life-threatening fungal infection of the central nervous
      system (CNS), predominantly in patients with a compromised immune system. Why
      Cryptococcus neoformans has this remarkable tropism for the CNS is not clear.
      Recent research on cerebral pathogenesis of C. neoformans revealed a
      predominantly transcellular migration of cryptococci across the brain
      endothelium; however, the identities of key fungal virulence factors that
      function specifically to invade the CNS remain unresolved. Here we found that a
      novel, secreted metalloprotease (Mpr1) that we identified in the extracellular
      proteome of C. neoformans (CnMpr1) is required for establishing fungal disease in
      the CNS. Mpr1 belongs to a poorly characterized M36 class of fungalysins that are
      expressed in only some fungal species. A strain of C. neoformans lacking the gene
      encoding Mpr1 (mpr1Delta) failed to breach the endothelium in an in vitro model
      of the human blood-brain barrier (BBB). A mammalian host infected with the
      mpr1Delta null strain demonstrated significant improvement in survival due to a
      reduced brain fungal burden and lacked the brain pathology commonly associated
      with cryptococcal disease. The in vivo studies further indicate that Mpr1 is not
      required for fungal dissemination and Mpr1 likely targets the brain endothelium
      specifically. Remarkably, the sole expression of CnMPR1 in Saccharomyces
      cerevisiae resulted in a robust migration of yeast cells across the brain
      endothelium, demonstrating Mpr1's specific activity in breaching the BBB and
      suggesting that Mpr1 may function independently of the hyaluronic acid-CD44
      pathway. This distinct role for Mpr1 may develop into innovative treatment
      options and facilitate a brain-specific drug delivery platform. IMPORTANCE:
      Cryptococcus neoformans is a medically relevant fungal pathogen causing
      significant morbidity and mortality, particularly in immunocompromised
      individuals. An intriguing feature is its strong neurotropism, and consequently
      the hallmark of cryptococcal disease is a brain infection, cryptococcal
      meningoencephalitis. For C. neoformans to penetrate the central nervous system
      (CNS), it first breaches the blood-brain barrier via a transcellular pathway;
      however, the identities of fungal factors required for this transmigration remain
      largely unknown. In an effort to identify extracellular fungal proteins that
      could mediate interactions with the brain endothelium, we undertook a proteomic
      analysis of the extracellular proteome and identified a secreted metalloprotease
      (Mpr1) belonging to the M36 class of fungalysins. Here we found that Mpr1
      promotes migration of C. neoformans across the brain endothelium and into the CNS
      by facilitating attachment of cryptococci to the endothelium surface, thus
      underscoring the critical role of M36 proteases in fungal pathogenesis.

PMID- 24895305
TI  - Mycobacterium tuberculosis Lsr2 is a global transcriptional regulator required
      for adaptation to changing oxygen levels and virulence.
AB  - To survive a dynamic host environment, Mycobacterium tuberculosis must endure a
      series of challenges, from reactive oxygen and nitrogen stress to drastic shifts
      in oxygen availability. The mycobacterial Lsr2 protein has been implicated in
      reactive oxygen defense via direct protection of DNA. To examine the role of Lsr2
      in pathogenesis and physiology of M. tuberculosis, we generated a strain deleted
      for lsr2. Analysis of the M. tuberculosis Deltalsr2 strain demonstrated that Lsr2
      is not required for DNA protection, as this strain was equally susceptible as the
      wild type to DNA-damaging agents. The lsr2 mutant did display severe growth
      defects under normoxic and hyperoxic conditions, but it was not required for
      growth under low-oxygen conditions. However, it was also required for adaptation
      to anaerobiosis. The defect in anaerobic adaptation led to a marked decrease in
      viability during anaerobiosis, as well as a lag in recovery from it. Gene
      expression profiling of the Deltalsr2 mutant under aerobic and anaerobic
      conditions in conjunction with published DNA binding-site data indicates that
      Lsr2 is a global transcriptional regulator controlling adaptation to changing
      oxygen levels. The Deltalsr2 strain was capable of establishing an early
      infection in the BALB/c mouse model; however, it was severely defective in
      persisting in the lungs and caused no discernible lung pathology. These findings
      demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required
      for control of genes involved in adaptation to extremes in oxygen availability
      and is required for persistent infection. IMPORTANCE: M. tuberculosis causes
      nearly two million deaths per year and infects nearly one-third of the world
      population. The success of this aerobic pathogen is due in part to its ability to
      successfully adapt to constantly changing oxygen availability throughout the
      infectious cycle, from the high oxygen tension during aerosol transmission to
      anaerobiosis within necrotic lesions. An understanding of how M. tuberculosis
      copes with these changes in oxygen tension is critical for its eventual
      eradication. Using a mutation in lsr2, we demonstrate that the Lsr2 protein
      present in all mycobacteria is a global transcriptional regulator in control of
      genes required for adaptation to changes in oxygen levels. M. tuberculosis
      lacking lsr2 was unable to adapt to both high and very low levels of oxygen and
      was defective in long-term anaerobic survival. Lsr2 was also required for disease
      pathology and for chronic infection in a mouse model of TB.

PMID- 24895306
TI  - Genome-wide identification of Acinetobacter baumannii genes necessary for
      persistence in the lung.
AB  - Acinetobacter baumannii is a Gram-negative bacterium that causes diseases such as
      pneumonia, bacteremia, and soft tissue infections in hospitalized patients.
      Relatively little is known about how A. baumannii causes these infections. Thus,
      we used insertion sequencing (INSeq), a combination of transposon mutagenesis and
      massively parallel next-generation sequencing, to identify novel virulence
      factors of A. baumannii. To this end, we generated a random transposon mutant
      library containing 150,000 unique insertions in A. baumannii strain ATCC 17978.
      The INSeq analysis identified 453 genes required for growth in rich medium. The
      library was then used in a murine pneumonia model, and the relative levels of
      abundance of mutants before and after selection in the mouse were compared. When
      genes required for growth in rich medium were removed from the analysis, 157
      genes were identified as necessary for persistence in the mouse lung. Several of
      these encode known virulence factors of A. baumannii, such as OmpA and ZnuB,
      which validated our approach. A large number of the genes identified were
      predicted to be involved in amino acid and nucleotide metabolism and transport.
      Other genes were predicted to encode an integration host factor, a transmembrane
      lipoprotein, and proteins involved in stress response and efflux pumps. Very few
      genes, when disrupted, resulted in an increase in A. baumannii numbers during
      host infection. The INSeq approach identified a number of novel virulence
      determinants of A. baumannii, which are candidate targets for therapeutic
      interventions. IMPORTANCE: A. baumannii has emerged as a frequent cause of
      serious infections in hospitals and community settings. Due to increasing
      antibiotic resistance, alternative approaches, such as antivirulence strategies,
      are desperately needed to fight A. baumannii infections. Thorough knowledge of A.
      baumannii pathogenicity is essential for such approaches but is currently
      lacking. With the increasingly widespread use of massively parallel sequencing, a
      class of techniques known as transposon insertion sequencing has been developed
      to perform comprehensive virulence screens of bacterial genomes in vivo. We have
      applied one of these approaches (INSeq) to uncover novel virulence factors in A.
      baumannii. We identified several such factors, including those predicted to
      encode amino acid and nucleotide metabolism proteins, an integration host factor
      protein, stress response factors, and efflux pumps. These results greatly expand
      the number of A. baumannii virulence factors and uncover potential targets for
      antivirulence treatments.

PMID- 24895307
TI  - Detecting nitrous oxide reductase (NosZ) genes in soil metagenomes: method
      development and implications for the nitrogen cycle.
AB  - Microbial activities in soils, such as (incomplete) denitrification, represent
      major sources of nitrous oxide (N2O), a potent greenhouse gas. The key enzyme for
      mitigating N2O emissions is NosZ, which catalyzes N2O reduction to N2. We
      recently described "atypical" functional NosZ proteins encoded by both
      denitrifiers and nondenitrifiers, which were missed in previous environmental
      surveys (R. A. Sanford et al., Proc. Natl. Acad. Sci. U. S. A. 109:19709-19714,
      2012, doi:10.1073/pnas.1211238109). Here, we analyzed the abundance and diversity
      of both nosZ types in whole-genome shotgun metagenomes from sandy and silty loam
      agricultural soils that typify the U.S. Midwest corn belt. First, different
      search algorithms and parameters for detecting nosZ metagenomic reads were
      evaluated based on in silico-generated (mock) metagenomes. Using the derived
      cutoffs, 71 distinct alleles (95% amino acid identity level) encoding typical or
      atypical NosZ proteins were detected in both soil types. Remarkably, more than
      70% of the total nosZ reads in both soils were classified as atypical,
      emphasizing that prior surveys underestimated nosZ abundance. Approximately 15%
      of the total nosZ reads were taxonomically related to Anaeromyxobacter, which was
      the most abundant genus encoding atypical NosZ-type proteins in both soil types.
      Further analyses revealed that atypical nosZ genes outnumbered typical nosZ genes
      in most publicly available soil metagenomes, underscoring their potential role in
      mediating N2O consumption in soils. Therefore, this study provides a
      bioinformatics strategy to reliably detect target genes in complex short-read
      metagenomes and suggests that the analysis of both typical and atypical nosZ
      sequences is required to understand and predict N2O flux in soils. IMPORTANCE:
      Nitrous oxide (N2O) is a potent greenhouse gas with ozone layer destruction
      potential. Microbial activities control both the production and the consumption
      of N2O, i.e., its conversion to innocuous dinitrogen gas (N2). Until recently,
      consumption of N2O was attributed to bacteria encoding "typical" nitrous oxide
      reductase (NosZ). However, recent phylogenetic and physiological studies have
      shown that previously uncharacterized, functional, "atypical" NosZ proteins are
      encoded in genomes of diverse bacterial groups. The present study revealed that
      atypical nosZ genes outnumbered their typical counterparts, highlighting their
      potential role in N2O consumption in soils and possibly other environments. These
      findings advance our understanding of the diversity of microbes and functional
      genes involved in the nitrogen cycle and provide the means (e.g., gene sequences)
      to study N2O fluxes to the atmosphere and associated climate change.

PMID- 24895308
TI  - Specialized transduction designed for precise high-throughput unmarked deletions
      in Mycobacterium tuberculosis.
AB  - Specialized transduction has proven to be useful for generating deletion mutants
      in most mycobacteria, including virulent Mycobacterium tuberculosis. We have
      improved this system by developing (i) a single-step strategy for the
      construction of allelic exchange substrates (AES), (ii) a temperature-sensitive
      shuttle phasmid with a greater cloning capacity than phAE87, and (iii)
      bacteriophage-mediated transient expression of site-specific recombinase to
      precisely excise antibiotic markers. The methods ameliorate rate-limiting steps
      in strain construction in these difficult-to-manipulate bacteria. The new methods
      for strain construction were demonstrated to generalize to all classes of genes
      and chromosomal loci by generating more than 100 targeted single- or multiple
      deletion substitutions. These improved methods pave the way for the generation of
      a complete ordered library of M. tuberculosis null strains, where each strain is
      deleted for a single defined open reading frame in M. tuberculosis. IMPORTANCE:
      This work reports major advances in the methods of genetics applicable to all
      mycobacteria, including but not limited to virulent M. tuberculosis, which would
      facilitate comparative genomics to identify drug targets, genetic validation of
      proposed pathways, and development of an effective vaccine. This study presents
      all the new methods developed and the improvements to existing methods in an
      integrated way. The work presented in this study could increase the pace of
      mycobacterial genetics significantly and will immediately be of wide use. These
      new methods are transformative and allow for the undertaking of construction of
      what has been one of the most fruitful resources in model systems: a
      comprehensive, ordered library set of the strains, each of which is deleted for a
      single defined open reading frame.

PMID- 24895309
TI  - Human genetic variation and yellow fever mortality during 19th century U.S.
      epidemics.
AB  - We calculated the incidence, mortality, and case fatality rates for Caucasians
      and non-Caucasians during 19th century yellow fever (YF) epidemics in the United
      States and determined statistical significance for differences in the rates in
      different populations. We evaluated nongenetic host factors, including
      socioeconomic, environmental, cultural, demographic, and acquired immunity status
      that could have influenced these differences. While differences in incidence
      rates were not significant between Caucasians and non-Caucasians, differences in
      mortality and case fatality rates were statistically significant for all
      epidemics tested (P < 0.01). Caucasians diagnosed with YF were 6.8 times more
      likely to succumb than non-Caucasians with the disease. No other major causes of
      death during the 19th century demonstrated a similar mortality skew toward
      Caucasians. Nongenetic host factors were examined and could not explain these
      large differences. We propose that the remarkably lower case mortality rates for
      individuals of non-Caucasian ancestry is the result of human genetic variation in
      loci encoding innate immune mediators. IMPORTANCE: Different degrees of severity
      of yellow fever have been observed across diverse populations, but this study is
      the first to demonstrate a statistically significant association between ancestry
      and the outcome of yellow fever (YF). With the global burden of mosquito-borne
      flaviviral infections, such as YF and dengue, on the rise, identifying and
      characterizing host factors could prove pivotal in the prevention of epidemics
      and the development of effective treatments.

PMID- 24895313
TI  - Molecular characterization of a novel hepcidin (HepcD) from Camelus dromedarius.
      Synthetic peptide forms exhibit antibacterial activity.
AB  - Hepcidin is a cysteine-rich peptide widely characterized in immunological
      processes and antimicrobial activity in several vertebrate species. Obviously,
      this hormone plays a central role in the regulation of systemic iron homeostasis.
      However, its role in camelids' immune response and whether it is involved in
      antibacterial immunity have not yet been proven. In this study, we characterized
      the Arabian camel hepcidin nucleotide sequence with an open reading frame of 252
      bp encoding an 83-amino acid preprohepcidin peptide. Eight cysteine key residues
      conserved in all mammalian hepcidin sequences were identified. The model
      structure analysis of hepcidin-25 peptide showed a high homology structure and
      sequence identity to the human hepcidin. Two different hepcidin-25 analogs
      manually synthesized by SPPS shared significant cytotoxic capacity toward the
      Gram-negative bacterium Escherichia coli American Type Culture Collection (ATCC)
      8739 as well as the Gram-positive bacteria Bacillus subtilis ATCC 11779 and
      Staphylococcus aureus ATCC 6538 in vitro. The three disulfide bridges hepcidin
      analog demonstrated bactericidal activity, against B. subtilis ATCC 11779 and S.
      aureus ATCC 6538 strains, at the concentration of 15 MUM (50 ug/ml) or above at
      pH 6.2. This result correlates with the revealed structural features suggesting
      that camel hepcidin is proposed to be involved in antibacterial process of innate
      immune response.

PMID- 24895310
TI  - Dietary pyridoxine controls efficacy of vitamin B6-auxotrophic tuberculosis
      vaccine bacillus Calmette-Guerin DeltaureC::hly Deltapdx1 in mice.
AB  - The only tuberculosis (TB) vaccine in use today, bacillus Calmette-Guerin (BCG),
      provides insufficient protection and can cause adverse events in
      immunocompromised individuals, such as BCGosis in HIV(+) newborns. We previously
      reported improved preclinical efficacy and safety of the recombinant vaccine
      candidate BCG DeltaureC::hly, which secretes the pore-forming listeriolysin O of
      Listeria monocytogenes. Here, we evaluate a second-generation construct, BCG
      DeltaureC::hly Deltapdx1, which is deficient in pyridoxine synthase, an enzyme
      that is required for biosynthesis of the essential cofactor vitamin B6. This
      candidate was auxotrophic for vitamin B6 in a concentration-dependent manner, as
      was its survival in vivo. BCG DeltaureC::hly Deltapdx1 showed markedly restricted
      dissemination in subcutaneously vaccinated mice, which was ameliorated by dietary
      supplementation with vitamin B6. The construct was safer in severe combined
      immunodeficiency mice than the parental BCG DeltaureC::hly. A prompt innate
      immune response to vaccination, measured by secretion of interleukin-6,
      granulocyte colony-stimulating factor, keratinocyte cytokine, and macrophage
      inflammatory protein-1alpha, remained independent of vitamin B6 administration,
      while acquired immunity, notably stimulation of antigen-specific CD4 T cells, B
      cells, and memory T cells, was contingent on vitamin B6 administration. The early
      protection provided by BCG DeltaureC::hly Deltapdx1 in a murine Mycobacterium
      tuberculosis aerosol challenge model consistently depended on vitamin B6
      supplementation. Prime-boost vaccination increased protection against the
      canonical M. tuberculosis H37Rv laboratory strain and a clinical isolate of the
      Beijing/W lineage. We demonstrate that the efficacy of a profoundly attenuated
      recombinant BCG vaccine construct can be modulated by external administration of
      a small molecule. This principle fosters the development of safer vaccines
      required for immunocompromised individuals, notably HIV(+) infants. IMPORTANCE:
      Mycobacterium tuberculosis can synthesize the essential cofactor vitamin B6,
      while humans depend on dietary supplementation. Unlike the lipophilic vitamins A,
      D, and E, water-soluble vitamin B6 is well tolerated at high doses. We generated
      a vitamin B6 auxotroph of the phase II clinical tuberculosis vaccine candidate
      bacillus Calmette-Guerin DeltaureC::hly. The next-generation candidate was
      profoundly attenuated compared to the parental strain. Adaptive immunity and
      protection in mice consistently depended on increased dietary vitamin B6 above
      the daily required dose. Control of vaccine efficacy via food supplements such as
      vitamin B6 could provide a fast track toward improved safety. Safer vaccines are
      urgently needed for HIV-infected individuals at high risk of adverse events in
      response to live vaccines.

PMID- 24895314
TI  - An update on the status of anatomical sciences education in United States medical
      schools.
AB  - Curricular changes continue at United States medical schools and directors of
      gross anatomy, microscopic anatomy, neuroscience/neuroanatomy, and embryology
      courses continue to adjust and modify their offerings. Developing and supplying
      data related to current trends in anatomical sciences education is important if
      informed decisions are going to be made in a time of curricular and course
      revision. Thus, a survey was sent to course directors during the 2012-2013
      academic years to gather information on total course hours, lecture and
      laboratory hours, the type of laboratory experiences, testing and competency
      evaluation, and the type of curricular approach used at their institution. The
      data gathered were compared to information obtained from previous surveys and
      conclusions reached were that only small or no change was observed in total
      course, lecture and laboratory hours in all four courses; more gross anatomy
      courses were part of an integrated curriculum since the previous survey; virtual
      microscopy with and without microscopes was the primary laboratory activity in
      microscopic anatomy courses; and neuroscience/neuroanatomy and embryology courses
      were unchanged.

PMID- 24895315
TI  - Role of p53 and EGFR as prognostic biomarkers in stage I non-small cell lung
      cancer.

PMID- 24895316
TI  - Comments on "Vacuum assisted closure therapy for treatment of complex wounds in
      replanted extremities".

PMID- 24895317
TI  - In vivo cell tracking of mouse embryonic myoblasts and fast fibers during
      development.
AB  - Fast and slow TnI are co-expressed in E11.5 embryos, and fast TnI is present from
      the very beginning of myogenesis. A novel green fluorescent protein (GFP)
      reporter mouse lines (FastTnI/GFP lines) that carry the primary and secondary
      enhancer elements of the mouse fast troponin I (fast TnI), in which reporter
      expression correlates precisely with distribution of the endogenous fTnI protein
      was generated. Using the FastTnI/GFP mouse model, we characterized the early
      myogenic events in mice, analyzing the migration of GFP+ myoblasts, and the
      formation of primary and secondary myotubes in transgenic embryos. Interestingly,
      we found that the two contractile fast and slow isoforms of TnI are expressed
      during the migration of myoblasts from the somites to the limbs and body wall,
      suggesting that both participate in these events. Since no sarcomeres are present
      in myoblasts, we speculate that the function of fast TnI in early myogenesis is,
      like Myosin and Tropomyosin, to participate in cell movement during the initial
      myogenic stages. genesis

PMID- 24895318
TI  - Specific detection of the floodwater mosquitoes Aedes sticticus and Aedes vexans
      DNA in predatory diving beetles.
AB  - Floodwater mosquitoes (Diptera: Culicidae) are associated with periodically
      flooded wet meadows, marshes, and swamps in floodplains of major rivers
      worldwide, and their larvae are abundant in the shallow parts of flooded areas.
      The nuisance caused by the blood-seeking adult female mosquitoes motivates
      mosquito control. Larviciding with Bacillus thuringiensis israelensis is
      considered the most environmentally safe method. However, some concern has been
      raised whether aquatic predatory insects could be indirectly affected by this
      reduction in a potential vital prey. Top predators in the temporary wetlands in
      the River Dalalven floodplains are diving beetles (Coleoptera: Dytiscidae), and
      Aedes sticticus and Ae. vexans are the target species for mosquito control. For
      detailed studies on this aquatic predator-prey system, we developed a polymerase
      chain reaction (PCR) assay for detection of mosquito DNA in the guts of medium
      sized diving beetles. Primers were designed for amplifying short mitochondrial
      DNA fragments of the cytochrome C oxidase subunit I (COI) gene in Ae. sticticus
      and Ae. vexans, respectively. Primer specificity was confirmed and half-life
      detectability of Ae. sticticus DNA in diving beetle guts was derived from a
      feeding and digestion experiment. The Ae. sticticus DNA within diving beetle guts
      was detected up to 12 h postfeeding, and half-life detectability was estimated to
      5.6 h. In addition, field caught diving beetles were screened for Ae. sticticus
      and Ae. vexans DNA and in 14% of the diving beetles one or both mosquito species
      were detected, showing that these mosquito species are utilized as food by the
      diving beetles. 

PMID- 24895319
TI  - Catalytic C-H amination: a reaction now accessible to engineered natural enzymes.

PMID- 24895320
TI  - The impact of colorectal cancer screening on the US population: is it time to
      celebrate?

PMID- 24895321
TI  - Differentiation between nerve and adipose tissue using wide-band (350-1,830 nm)
      in vivo diffuse reflectance spectroscopy.
AB  - BACKGROUND: Intraoperative nerve localization is of great importance in surgery.
      In certain procedures, where nerves show visual resemblance to surrounding
      adipose tissue, this can be particularly challenging for the human eye. An
      example of such a delicate procedure is thyroid and parathyroid surgery, where
      iatrogenic injury of the recurrent laryngeal nerve can result in transient or
      permanent vocal problems (0.5-2.0% reported incidence). A camera system, enabling
      nerve-specific image enhancement, would be useful in preventing such
      complications. This might be realized with hyperspectral camera technology using
      silicon (Si) or indium gallium arsenide (InGaAs) sensor chips. METHODS: As a
      first step towards such a camera, we evaluated the performance of diffuse
      reflectance spectroscopy by analysing spectra collected during 18 thyroid and
      parathyroid resections. We assessed the contrast information present in two
      different spectral ranges, for respectively Si and InGaAs sensors. Two hundred
      fifty three in vivo, wide-band diffuse reflectance spectra (350-1,830 nm range, 1
      nm resolution) were acquired on 52 tissue spots, including nerve (n = 22), muscle
      (n = 12), and adipose tissue (n = 18). We extracted 36 features from these
      spectroscopic data: 18 gradients and 18 amplitude differences at predefined
      points in the tissue spectra. Best distinctive feature combinations were
      established using binary logistic regression. Classification performance was
      evaluated in a cross-validation (CV) approach by leave-one-out (LOO). To
      generalize nerve recognition applicability, we performed a train-test (TT)
      validation using the thyroid and parathyroid surgery data for training purposes
      and carpal tunnel release surgery data (10 nerve spots and 5 adipose spots) for
      classification purposes. RESULTS: For combinations of two distinctive spectral
      features, LOO revealed an accuracy of respectively 78% for Si-sensors and 95% for
      InGaAs-sensors. TT revealed accuracies of respectively 67% and 100%. CONCLUSIONS:
      Using diffuse reflectance spectroscopy we have identified that InGaAs sensors are
      better suited for automated discrimination between nerves and surrounding adipose
      tissue than Si sensors.

PMID- 24895322
TI  - Intrinsic chirality and prochirality at Air/R-(+)- and S-(-)-limonene interfaces:
      spectral signatures with interference chiral sum-frequency generation vibrational
      spectroscopy.
AB  - We report in this work detailed measurements of the chiral and achiral sum
      frequency vibrational spectra in the C-H stretching vibration region (2800-3050
      cm(-1)) of the air/liquid interfaces of R-(+)-limonene and S-(-)-limonene, using
      the recently developed high-resolution broadband sum-frequency generation
      vibrational spectroscopy (HR-BB-SFG-VS). The achiral SFG spectra of R-limonene
      and S-limonene, as well as the RS racemic mixture (50/50 equal amount mixture),
      show that the corresponding molecular groups of the R and S enantiomers are with
      the same interfacial orientations. The interference chiral SFG spectra of the
      limonene enantiomers exhibit a spectral signature from the chiral response of the
      Calpha-H stretching mode, and a spectral signature from the prochiral response of
      the CH(2) asymmetric stretching mode, respectively. The chiral spectral feature
      of the Calpha-H stretching mode changes sign from R-(+)-limonene to S-(-)
      limonene surfaces, and disappears for the RS racemic mixture surface. While the
      prochiral spectral feature of the CH(2) asymmetric stretching mode is the same
      for R-(+)-limonene and S-(-)-limonene surfaces, and also surprisingly remains the
      same for the RS racemic mixture surface. Therefore, the structures of the R-(+)
      limonene and the S-(-)-limonene at the liquid interfaces are nevertheless not
      mirror images to each other, even though the corresponding groups have the same
      tilt angle from the interfacial normal, i.e., the R-(+)-limonene and the S-(-)
      limonene at the surface are diastereomeric instead of enantiomeric. These results
      provide detailed information in understanding the structure and chirality of
      molecular interfaces and demonstrate the sensitivity and potential of SFG-VS as a
      unique spectroscopic tool for chirality characterization and chiral recognition
      at the molecular interface.

PMID- 24895323
TI  - Structural and optical properties of short peptides: nanotubes-to-nanofibers
      phase transformation.
AB  - Thermally induced phase transformation in bioorganic nanotubes, which self
      assembled from two ultrashort dipeptides of different origin, aromatic
      diphenylalanine (FF) and aliphatic dileucine (LL), is studied. In both FF and LL
      nanotubes, irreversible phase transformation found at 120-180  degrees C is
      governed by linear-to-cyclic dipeptide molecular modification followed by
      formation of extended beta-sheet structure. As a result of this process, native
      open-end FF and LL nanotubes are transformed into ultrathin nanofibrils. Found
      deep reconstructions at all levels from macroscopic (morphology) and structural
      space symmetry to molecular give rise to new optical properties in both aromatic
      FF and aliphatic LL nanofibrils and generation of blue photoluminescence (PL)
      emission. It is shown that observed blue PL peak is similar in these
      supramolecular nanofibrillar structures and is excited by the network of non
      covalent hydrogen bonds that link newly thermally induced neighboring cyclic
      dipeptide strands to final extended beta-sheet structure of amyloid-like
      nanofibrils. The observed blue PL peak in short dipeptide nanofibrils is similar
      to the blue PL peak that was recently found in amyloid fibrils and can be
      considered as the optical signature of beta-sheet structures. Nanotubular
      structures were characterized by environmental scanning electron microscope, ToF
      secondary ion mass spectroscopy, CD and fluorescence spectroscopy.

PMID- 24895324
TI  - Remote trap passivation in colloidal quantum dot bulk nano-heterojunctions and
      its effect in solution-processed solar cells.
AB  - More-efficient charge collection and suppressed trap recombination in colloidal
      quantum dot (CQD) solar cells is achieved by means of a bulk nano-heterojunction
      (BNH) structure, in which p-type and n-type materials are blended on the
      nanometer scale. The improved performance of the BNH devices, compared with that
      of bilayer devices, is displayed in higher photocurrents and higher open-circuit
      voltages (resulting from a trap passivation mechanism). 

PMID- 24895325
TI  - Inactivation of the catalytic phosphatase domain of PTPRT/RPTPrho increases
      social interaction in mice.
AB  - Receptor protein tyrosine phosphatase rho (RPTPrho, gene symbol PTPRT) is a
      transmembrane protein expressed at high levels in the developing hippocampus,
      olfactory bulb, cortex, and cerebellum. It has an extracellular domain that
      interacts with other cell adhesion molecules, and it has two intracellular
      phosphatase domains, one of which is catalytically active. In a recent genome
      wide association study, PTPRT was identified as a potential candidate gene for
      autism spectrum disorder (ASD) susceptibility. Mutation of a critical aspartate
      to alanine (D1046A) in the PTPRT catalytic domain inactivates phosphatase
      function but retains substrate binding. We have generated a knockin mouse line
      carrying the PTPRT D1046A mutation. The D1046A mutation in homozygous knockin
      mice did not significantly change locomotor activities or anxiety-related
      behaviors. In contrast, male homozygous mice had significantly higher social
      approach scores than wild-type animals. Our results suggest that PTPRT
      phosphatase function is important in modulating neural pathways involved in mouse
      social behaviors relevant to the symptoms in human ASD patients.

PMID- 24895327
TI  - Super-microdissected local flaps for the coverage of temporal defects.
AB  - INTRODUCTION: Skin graft is still a method of choice for the coverage of temporal
      defects. But there are some disadvantages like a "patch" appearance, the need of
      dressing or longer healing time. Numbers of local flaps have been described for
      closing skin defects on temporal region. Yet, they may cause distortion of the
      surrounding tissues, especially in the temporal hairline and eyebrow. We present
      a series of seven local flaps based on small branches (SB) of the superficial
      temporal artery (STA) for the coverage of temporal defects, and discuss their
      advantages. PATIENTS AND METHODS: Supermicrodissection of SB of the STA was
      performed to obtain local flaps for reconstruction of temporal defects after skin
      cancer excisions in seven patients. Patient's age ranged from 70 to 88 years old
      and the diameter of defects ranged from 4 to 6 cm. All procedures were performed
      under local anesthesia except one. In all cases, defects were obtained after skin
      cancer excisions. RESULTS: The operative time ranged from 55 to 75 min. All flaps
      survived with an average follow-up of 8 months, reconstructions have maintained a
      cosmetically pleasing result. CONCLUSION: We believe that SB flaps may be a new
      option for reconstruction of temporal defects with the advantages of local flaps,
      without the inconvenience of a skin pedicle. Moreover, these flaps raise the
      question of the use of SB based flaps for the coverage of moderate-sized skin
      defects anywhere in the body, and open new fields in reconstructive surgery.

PMID- 24895326
TI  - The microRNA-200 family--a potential diagnostic marker in hepatocellular
      carcinoma?
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) represents the main cause of death
      among patients with cirrhotic liver disease, but little is known about mechanisms
      of cirrhosis associated carcinogenesis. We investigated the diagnostic impact of
      microRNA-200 (miR-200) family members as important epigenetic regulators of
      epithelial-mesenchymal transition (EMT) to differentiate between patients with
      HCC and liver cirrhosis. METHODS: Expression of the miR-200 family was
      investigated by qRT-PCR in specimens of HCC patients with and without cirrhosis.
      Benign specimens with and without cirrhosis served as controls. Expression of the
      EMT markers ZEB-1, E-cadherin and vimentin was examined using
      immunohistochemistry. RESULTS: MiR-200a and miR-200b were significantly
      downregulated in HCC (miR-200a: -40.1% (P = 0.0002); miR-200b: -52.3% (P =
      0.0002)), and in HCC cirrhotic tissue (miR-200a: -40.2% (P = 0.004); miR-200b: 
      51.1% (P = 0.007)) compared to liver cirrhosis. Spearman's Rho analysis revealed
      a significant negative correlation of miR-200a and miR-200b to the expression of
      the mesenchymal markers Vimentin (P < 0.007) and ZEB-1 (P < 0.0005) and a
      significant positive correlation to the epithelial marker E-cadherin (P <
      0.0002). CONCLUSIONS: MiR-200 family members and their targets are significantly
      deregulated in HCC and liver cirrhosis. The miR-200 family is able to distinguish
      between cirrhotic and HCC tissue and could serve as an early marker for cirrhosis
      associated HCC.

PMID- 24895329
TI  - Principles of representation: why you can't represent the same concept twice.
AB  - As embodied theories of cognition are increasingly formalized and tested, care
      must be taken to make informed assumptions regarding the nature of concepts and
      representations. In this study, we outline three reasons why one cannot, in
      effect, represent the same concept twice. First, online perception affects
      offline representation: Current representational content depends on how ongoing
      demands direct attention to modality-specific systems. Second, language is a
      fundamental facilitator of offline representation: Bootstrapping and shortcuts
      within the computationally cheaper linguistic system continuously modify
      representational content. Third, time itself is a source of representational
      change: As the content of underlying concepts shifts with the accumulation of
      direct and vicarious experience, so too does the content of representations that
      draw upon these concepts. We discuss the ramifications of these principles for
      research into both human and synthetic cognitive systems. 

PMID- 24895328
TI  - Distinguishing unfolding and functional conformational transitions of calmodulin
      using ultraviolet resonance Raman spectroscopy.
AB  - Calmodulin (CaM) is a ubiquitous moderator protein for calcium signaling in all
      eukaryotic cells. This small calcium-binding protein exhibits a broad range of
      structural transitions, including domain opening and folding-unfolding, that
      allow it to recognize a wide variety of binding partners in vivo. While the
      static structures of CaM associated with its various binding activities are
      fairly well-known, it has been challenging to examine the dynamics of transition
      between these structures in real-time, due to a lack of suitable spectroscopic
      probes of CaM structure. In this article, we examine the potential of ultraviolet
      resonance Raman (UVRR) spectroscopy for clarifying the nature of structural
      transitions in CaM. We find that the UVRR spectral change (with 229 nm
      excitation) due to thermal unfolding of CaM is qualitatively different from that
      associated with opening of the C-terminal domain in response to Ca(2+) binding.
      This spectral difference is entirely due to differences in tertiary contacts at
      the interdomain tyrosine residue Tyr138, toward which other spectroscopic methods
      are not sensitive. We conclude that UVRR is ideally suited to identifying the
      different types of structural transitions in CaM and other proteins with
      conformation-sensitive tyrosine residues, opening a path to time-resolved studies
      of CaM dynamics using Raman spectroscopy. 

PMID- 24895330
TI  - Optical control of acetylcholinesterase with a tacrine switch.
AB  - Photochromic ligands have been used to control a variety of biological functions,
      especially in neural systems. Recently, much effort has been invested in the
      photocontrol of ion channels and G-protein coupled receptors found in the
      synapse. Herein, we describe the expansion of our photopharmacological approach
      toward the remote control of an enzyme. Building on hallmark studies dating from
      the late 1960s, we evaluated photochromic inhibitors of one of the most important
      enzymes in synaptic transmission, acetylcholinesterase (AChE). Using structure
      based design, we synthesized several azobenzene analogues of the well-known AChE
      inhibitor tacrine (THA) and determined their effects on enzymatic activity. One
      of our compounds, AzoTHA, is a reversible photochromic blocker of AChE in vitro
      and ex vivo with high affinity and fast kinetics. As such, AzoTHA can be used to
      control synaptic transmission on the neuromuscular endplate based on the light
      dependent clearance of a neurotransmitter. 

PMID- 24895331
TI  - Impaired neural drive in patients with low back pain.
AB  - BACKGROUND: Control of trunk movement relies on the integration between central
      neuronal circuits and peripheral skeletomuscular activities and it can be altered
      by pain. There is increasing evidence that there are deficits within the central
      nervous system controlling the trunk muscles in people with low back pain (LBP).
      However, it is unclear how LBP impacts upon neural drive to back muscles at
      different levels of voluntary contraction. Therefore, the purpose of this study
      was to investigate if neural drive is impaired in these patients. METHODS:
      Seventeen patients with LBP and 11 healthy controls were recruited. Bilateral
      electromyographic (EMG) recordings were obtained from the erector spinae (ES)
      muscles at two vertebral levels (T12 and L4). Participants performed a series of
      brief isometric back extensions (50-100% maximum voluntary contraction - MVC),
      during which transcranial magnetic stimulation was delivered. The size of the
      evoked (superimposed) twitch was measured using dynamometry. RESULTS: The size of
      the superimposed twitch decreased linearly with increasing contraction strength
      in the controls; however, this linear relationship was not observed in the
      patients. Additionally, patients had larger superimposed twitches and longer time
      to-peak amplitudes during MVCs than those observed in controls. Furthermore,
      patients had lower MVC and root-mean-square EMG activity of ES muscles during
      MVCs. CONCLUSIONS: A decline of central neural drive to the back muscles at high
      level of voluntary contraction was observed in patients with LBP. These results
      suggest that it might be pertinent to include neuromuscular facilitation
      programmes and therapeutic exercise utilizing high voluntary contractions for
      patients with LBP.

PMID- 24895332
TI  - The variation of psychopharmacological prescription rates for people with autism
      spectrum disorder (ASD) in 30 countries.
AB  - There is significant variation in prescriptions among countries in clinical
      practice for the treatment of comorbidities associated with autism spectrum
      disorder (ASD). It has been suggested that many people with mental health
      disorders in low-/middle-income countries do not receive adequate treatment.
      Hence, this study investigated psychopharmacological treatment patterns for ASD
      comorbidities in 30 countries and the association between country's income and
      prescription rates. The IMS Prescribing Insights database was used to investigate
      prescription patterns for ASD comorbidity treatment from 2007 to 2012. Data were
      obtained from 30 countries in continents of Europe, Asia, Oceania, Central
      America, South America, and Africa. The gross domestic product (GDP) per capita
      was used as a proxy for each country's income. Spearman correlation was used to
      examine the association between prescription rate and GDP per capita. The highest
      prescription rates were found in Western Europe (3.89-36.36/10,000) while the
      lowest prescription rates were found in Asian countries, such as Turkey,
      Indonesia, Saudi Arabia, and Pakistan (0.04-0.82/10,000). The most commonly
      prescribed drug for ASD comorbidity treatment in most of the countries was
      risperidone, but antidepressants and antiepileptic drugs were also frequently
      prescribed. There was a significant positive correlation between GDP per capita
      and prescription rate (Spearman rho = 0.60; P = 0.0011; 95% confidence interval
      0.27-0.81), that is, the higher the GDP per capita, the higher the prescription
      rate. There are marked international differences in prescription rates, and this
      is partially accounted by economic factors. Future research should combine more
      data for ASD comorbidity treatment to explore the disparity of
      psychopharmacological treatment between countries.

PMID- 24895334
TI  - Chirality induction and amplification in the 2,2,2-trifluoroethanol???propylene
      oxide adduct.
AB  - Chirality induction and amplification in a model system, that is, the 2,2,2
      trifluoroethanol (TFE)???propylene oxide (PO) adduct, were investigated using
      free-space and cavity-based Fourier transform microwave spectroscopy,
      complemented with high level ab initio calculations. Rotational spectra of four
      out of eight predicted TFE??PO adducts were assigned, and the remaining four were
      shown to relax to the geometries of the four observed in a jet expansion. The g+
      TFE???S-PO adduct was found to be favored over that of g- TFE???S-PO by a factor
      of 2.8 at 60 K. This difference contrasts the TFE dimer for which an extreme case
      of chirality synchronization was previously reported. All TFE???PO conformers
      observed take on the open arrangement, in contrast to 2-fluoroethanol???PO, which
      prefers the closed arrangement. Furthermore, perfluorination at CH3 increases the
      hydrogen-bonding energy by about 70 % over its ethanol counterpart. 

PMID- 24895333
TI  - Fine tuning of the catalytic activity of colicin E7 nuclease domain by systematic
      N-terminal mutations.
AB  - The nuclease domain of colicin E7 (NColE7) promotes the nonspecific cleavage of
      nucleic acids at its C-terminal HNH motif. Interestingly, the deletion of four N
      terminal residues (446-449 NColE7 = KRNK) resulted in complete loss of the enzyme
      activity. R447A mutation was reported to decrease the nuclease activity, but a
      detailed analysis of the role of the highly positive and flexible N-terminus is
      still missing. Here, we present the study of four mutants, with a decreased
      activity in the following order: NColE7  >> KGNK > KGNG ~ GGNK > GGNG. At the
      same time, the folding, the metal-ion, and the DNA-binding affinity were
      unaffected by the mutations as revealed by linear and circular dichroism
      spectroscopy, isothermal calorimetric titrations, and gel mobility shift
      experiments. Semiempirical quantum chemical calculations and molecular dynamics
      simulations revealed that K446, K449, and/or the N-terminal amino group are able
      to approach the active centre in the absence of the other positively charged
      residues. The results suggested a complex role of the N-terminus in the catalytic
      process that could be exploited in the design of a controlled nuclease. 

PMID- 24895335
TI  - Hepcidin as a predictive factor and therapeutic target in erythropoiesis
      stimulating agent treatment for anemia of chronic disease in rats.
AB  - Anemia of chronic disease is a multifactorial disorder, resulting mainly from
      inflammation-driven reticuloendothelial iron retention, impaired erythropoiesis,
      and reduced biological activity of erythropoietin. Erythropoiesis-stimulating
      agents have been used for the treatment of anemia of chronic disease, although
      with varying response rates and potential adverse effects. Serum concentrations
      of hepcidin, a key regulator of iron homeostasis, are increased in patients with
      anemia of chronic disease and linked to the pathogenesis of this disease, because
      hepcidin blocks cellular iron egress, thus limiting availability of iron for
      erythropoiesis. We tested whether serum hepcidin levels can predict and affect
      the therapeutic efficacy of erythropoiesis-stimulating agent treatment using a
      well-established rat model of anemia of chronic disease. We found that high pre
      treatment hepcidin levels correlated with an impaired hematologic response to an
      erythropoiesis-stimulating agent in rats with anemia of chronic disease. Combined
      treatment with an erythropoiesis-stimulating agent and an inhibitor of hepcidin
      expression, LDN-193189, significantly reduced serum hepcidin levels, mobilized
      iron from tissue stores, increased serum iron levels and improved hemoglobin
      levels more effectively than did the erythropoiesis-stimulating agent or LDN
      193189 monotherapy. In parallel, both the erythropoiesis-stimulating agent and
      erythropoiesis-stimulating agent/LDN-193189 combined reduced the expression of
      cytokines known to inhibit erythropoiesis. We conclude that serum hepcidin levels
      can predict the hematologic responsiveness to erythropoiesis-stimulating agent
      therapy in anemia of chronic disease. Pharmacological inhibition of hepcidin
      formation improves the erythropoiesis-stimulating agent's therapeutic efficacy,
      which may favor a reduction of erythropoiesis-stimulating agent dosages, costs
      and side effects. 

PMID- 24895336
TI  - Distinct clinical characteristics of myeloproliferative neoplasms with
      calreticulin mutations.
AB  - Somatic insertions/deletions in the calreticulin gene have recently been
      discovered to be causative alterations in myeloproliferative neoplasms. A
      combination of qualitative and quantitative allele-specific polymerase chain
      reaction, fragment-sizing, high resolution melting and Sanger-sequencing was
      applied for the detection of three driver mutations (in Janus kinase 2,
      calreticulin and myeloproliferative leukemia virus oncogene genes) in 289 cases
      of essential thrombocythemia and 99 cases of primary myelofibrosis. In essential
      thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%)
      myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple
      negative (11%) cases were identified, while in primary myelofibrosis 56 (57%)
      Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia
      virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were
      identified. Patients positive for the calreticulin mutation were younger and had
      higher platelet counts compared to Janus kinase 2 mutation-positive counterparts.
      Calreticulin mutation-positive patients with essential thrombocythemia showed a
      lower risk of developing venous thrombosis, but no difference in overall
      survival. Calreticulin mutation-positive patients with primary myelofibrosis had
      a better overall survival compared to that of the Janus kinase 2 mutation
      positive (P=0.04) or triple-negative cases (P=0.01). Type 2 calreticulin mutation
      occurred more frequently in essential thrombocythemia than in primary
      myelofibrosis (P=0.049). In essential thrombocythemia, the calreticulin
      mutational load was higher than the Janus kinase 2 mutational load (P<0.001), and
      increased gradually in advanced stages. Calreticulin mutational load influenced
      blood counts even at the time point of diagnosis in essential thrombocythemia. We
      confirm that calreticulin mutation is associated with distinct clinical
      characteristics and explored relationships between mutation type, load and
      clinical outcome. 

PMID- 24895337
TI  - MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic
      leukemia.
AB  - T-cell acute lymphoblastic leukemia arises from the leukemic transformation of
      developing thymocytes and results from cooperative genetic lesions. Inactivation
      of the PHF6 gene is frequently observed in T-cell acute lymphoblastic leukemia,
      suggesting an important tumor suppressive role for PHF6 in the pathobiology of
      this leukemia. Although the precise function of PHF6 is still unknown, this gene
      is most likely involved in chromatin regulation, a strongly emerging theme in T
      cell acute lymphoblastic leukemia. In this context, our previous description of a
      cooperative microRNA regulatory network controlling several well-known T-cell
      acute lymphoblastic leukemia tumor suppressor genes, including PHF6, is of great
      importance. Given the high frequency of PHF6 lesions in T-cell acute
      lymphoblastic leukemia and the integration of PHF6 in this microRNA regulatory
      network, we aimed to identify novel oncogenic microRNAs in T-cell acute
      lymphoblastic leukemia which suppress PHF6. To this end, we performed an unbiased
      PHF6 3'UTR-microRNA library screen and combined the results with microRNA
      profiling data of samples from patients with T-cell acute lymphoblastic leukemia
      and normal thymocyte subsets. We selected miR-128-3p as a candidate PHF6
      targeting, oncogenic microRNA and demonstrated regulation of PHF6 expression upon
      modulation of this microRNA in T-cell acute lymphoblastic leukemia cell lines. In
      vivo evidence of an oncogenic role of this microRNA in T-cell acute lymphoblastic
      leukemia was obtained through accelerated leukemia onset in a NOTCH1-induced T
      cell acute lymphoblastic leukemia mouse model upon miR-128-3p over-expression. We
      conclude that miR-128-3p is a strong novel candidate oncogenic microRNA in T-cell
      acute lymphoblastic leukemia which targets the PHF6 tumor suppressor gene. 

PMID- 24895338
TI  - Impact of MLL5 expression on decitabine efficacy and DNA methylation in acute
      myeloid leukemia.
AB  - Hypomethylating agents are widely used in patients with myelodysplastic syndromes
      and unfit patients with acute myeloid leukemia. However, it is not well
      understood why only some patients respond to hypomethylating agents. We found
      previously that the effect of decitabine on hematopoietic stem cell viability
      differed between Mll5 wild-type and null cells. We, therefore, investigated the
      role of MLL5 expression levels on outcome of acute myeloid leukemia patients who
      were treated with decitabine. MLL5 above the median expression level predicted
      longer overall survival independent of DNMT3A mutation status in bivariate
      analysis (median overall survival for high vs. low MLL5 expression 292 vs. 167
      days; P=0.026). In patients who received three or more courses decitabine, high
      MLL5 expression and wild-type DNMT3A independently predicted improved overall
      survival (median overall survival for high vs. low MLL5 expression 468 vs. 243
      days; P=0.012). In transformed murine cells, loss of Mll5 was associated with
      resistance to low-dose decitabine, less global DNA methylation in promoter
      regions, and reduced DNA demethylation upon decitabine treatment. Together, these
      data support our clinical observation of improved outcome in decitabine-treated
      patients who express MLL5 at high levels, and suggest a mechanistic role of MLL5
      in the regulation of DNA methylation. 

PMID- 24895339
TI  - R-CHOP with or without bevacizumab in patients with previously untreated diffuse
      large B-cell lymphoma: final MAIN study outcomes.
AB  - Vascular endothelial growth factor is involved in lymphoma growth, suggesting a
      potential role for anti-vascular endothelial growth factor therapies in
      hematologic malignancies. In this phase III study, patients with CD20-positive
      diffuse large B-cell lymphoma were randomized to rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisone plus either placebo (R-CHOP) or
      bevacizumab (RA-CHOP). Treatment was administered every 21 (8 cycles) or 14 days
      (6 cycles plus 2 rituximab cycles) as per institutional practice. An early
      analysis of risk/benefit by the Data and Safety Monitoring Board showed that RA
      CHOP increased cardiotoxicity without prolonging progression-free survival
      compared with R-CHOP, and the trial was stopped early. The study protocol was
      amended to allow for 12 additional months of follow up to evaluate safety. With
      787 patients enrolled, median follow up was 23.7 and 23.6 months for R-CHOP and
      RA-CHOP, respectively. Median progression-free survival for R-CHOP and RA CHOP
      was 42.9 and 40.2 months, respectively (hazard ratio=1.09; P=0.49). The
      proportion of deaths was identical for R-CHOP (83 of 387, 21%) and RA-CHOP (82 of
      390, 21%). Relative to R-CHOP, RA-CHOP had a higher rate of left ventricular
      ejection fraction perturbation (18% vs. 8%; odds ratio=2.51; 95% confidence
      interval (CI): 1.60-3.93) and congestive heart failure (16% vs. 7%; odds
      ratio=2.79; 95%CI: 1.72-4.54). Bevacizumab added to R-CHOP increased cardiac
      events, without increasing efficacy, arguing against further evaluation of RA
      CHOP in patients with diffuse large B-cell lymphoma. The MAIN study is registered
      at clinicaltrials.gov identifier:00486759. 

PMID- 24895340
TI  - Hematologic parameters predicting a response to oral iron therapy in chronic
      inflammation.

PMID- 24895341
TI  - Severe nondominant hereditary spherocytosis due to uniparental isodisomy at the
      SPTA1 locus.

PMID- 24895350
TI  - Monitoring the ability to deliver care in low- and middle-income countries: a
      systematic review of health facility assessment tools.
AB  - INTRODUCTION: Health facilities assessments are an essential instrument for
      health system strengthening in low- and middle-income countries. These
      assessments are used to conduct health facility censuses to assess the capacity
      of the health system to deliver health care and to identify gaps in the coverage
      of health services. Despite the valuable role of these assessments, there are
      currently no minimum standards or frameworks for these tools. METHODS: We used a
      structured keyword search of the MEDLINE, EMBASE and HealthStar databases and
      searched the websites of the World Health Organization, the World Bank and the
      International Health Facilities Assessment Network to locate all available health
      facilities assessment tools intended for use in low- and middle-income countries.
      We parsed the various assessment tools to identify similarities between them,
      which we catalogued into a framework comprising 41 assessment domains. RESULTS:
      We identified 10 health facility assessment tools meeting our inclusion criteria,
      all of which were included in our analysis. We found substantial variation in the
      comprehensiveness of the included tools, with the assessments containing
      indicators in 13 to 33 (median: 25.5) of the 41 assessment domains included in
      our framework. None of the tools collected data on all 41 of the assessment
      domains we identified. CONCLUSIONS: Not only do a large number of health facility
      assessment tools exist, but the data they collect and methods they employ are
      very different. This certainly limits the comparability of the data between
      different countries' health systems and probably creates blind spots that impede
      efforts to strengthen those systems. Agreement is needed on the essential
      elements of health facility assessments to guide the development of specific
      indicators and for refining existing instruments.

PMID- 24895351
TI  - Evaluating place-based programmes for health improvement.

PMID- 24895352
TI  - Incidence and predictors of sudden cardiac death in patients with reduced left
      ventricular ejection fraction after myocardial infarction in an era of
      revascularisation.
AB  - OBJECTIVE: To determine the incidence and predictors of sudden cardiac death
      (SCD) in the current era of revascularisation of myocardial infarction (MI)
      survivors with reduced LVEF. METHODS: A prospective observational study was
      conducted in FuWai Hospital from 2004 to 2009. A total of 1018 consecutive
      patients who had an LVEF <=35% and New York Heart Association Class II/III heart
      failure at least 40 days after MI were enrolled if they were not available for
      implantation of an implantable cardioverter defibrillator. The degree of coronary
      artery disease and revascularisation were analysed. The primary outcome was SCD
      and secondary outcome was all-cause death. RESULTS: During a mean follow-up of
      2.8 years, the SCD rate was 5% and all-cause mortality was 7.4%. The annual
      incidence of SCD was 1.8%. Kaplan-Meier analysis showed that the cumulative rate
      of SCD was significantly increased in patients with triple-vessel disease (6.7%
      vs 0.6%), left main coronary disease (10.3% vs 4.1%), EF <=25% (8.3% vs 3.9%) and
      non-revascularisation therapy (9.6% vs 2.7%) (all log-rank, p<0.05). After
      multivariable Cox regression analysis, the risk of SCD was predicted by age (HR
      1.05, 95% CI 1.02 to 1.09), EF <=25% (HR 1.82, 95% CI 1.04 to 3.21) and non
      revascularisation (HR 3.97, 95% CI 2.15 to 7.31). CONCLUSIONS: Revascularisation
      may reduce the risk of SCD in post-MI patients with an LVEF <=35% on the basis of
      medical therapy, and the increased risk for SCD may be predicted by age, LVEF
      <=25% and non-revascularisation.

PMID- 24895349
TI  - microRNAs and HDL life cycle.
AB  - miRNAs have emerged as important regulators of lipoprotein metabolism. Work over
      the past few years has demonstrated that miRNAs control the expression of most of
      the genes associated with high-density lipoprotein (HDL) metabolism, including
      the ATP transporters, ABCA1 and ABCG1, and the scavenger receptor SRB1. These
      findings strongly suggest that miRNAs regulate HDL biogenesis, cellular
      cholesterol efflux, and HDL cholesterol (HDL-C) uptake in the liver, thereby
      controlling all of the steps of reverse cholesterol transport. Recent work in
      animal models has demonstrated that manipulating miRNA levels including miR-33
      can increase circulating HDL-C. Importantly, antagonizing miR-33 in vivo enhances
      the regression and reduces the progression of atherosclerosis. These findings
      support the idea of developing miRNA inhibitors for the treatment of
      dyslipidaemia and related cardiovascular disorders such as atherosclerosis. This
      review article focuses on how HDL metabolism is regulated by miRNAs and how
      antagonizing miRNA expression could be a potential therapy for treating
      cardiometabolic diseases. 

PMID- 24895353
TI  - Considerations on the poor discriminatory power of the FRANCE-2 risk score.

PMID- 24895354
TI  - Predictors of 1-year mortality in patients with aortic regurgitation after
      transcatheter aortic valve implantation: an analysis from the multicentre German
      TAVI registry.
AB  - OBJECTIVE: Residual aortic regurgitation (AR) after transcatheter aortic valve
      implantation (TAVI) has been associated with increased mortality. Nevertheless, a
      considerable proportion of these patients survives and appears to tolerate AR.
      Identification of patients at higher risk of death may assist in tailoring
      therapy, but predictors of mortality in this subset of patients is largely
      unknown. METHODS: A total of 1432 patients were included in the German TAVI
      registry. One-year follow-up data were available for 1318 patients (92%). Of the
      latter, 201 patients (15.2%) had more-than-mild AR as evaluated by angiography
      and represent the population of the current analysis. Among these patients,
      baseline demographic, clinical, echocardiographic and angiographic
      characteristics were compared among survivors and non-survivors to identify
      factors associated with mortality at 1 year. RESULTS: Mean age was 81.2+/-6.6
      years and men represented 55%. The mean logistic EuroSCORE was 22+/-15%. Overall,
      92% of patients received the Medtronic CoreValve and 8% received the Edwards
      Sapien valve. At 1 year, 61 patients (31%) with more-than-mild post-TAVI AR had
      died. Compared with patients who survived, patients who died had more commonly
      coronary artery disease, peripheral arterial disease and chronic renal
      impairment. Patients who died had a lower baseline LVEF (44+/-18% vs 52+/-16%,
      p=0.002), higher prevalence of more-than-mild (>=2+) mitral regurgitation (44% vs
      27%, p=0.001), and a higher systolic pulmonary artery pressure (51+/-18 mm Hg vs
      44+/-19 mm Hg, p=0.002), but the severity of aortic stenosis was similar, and the
      prevalence and severity of pre-TAVI AR was comparable (any AR in 88% vs 83%,
      respectively, p=0.29). Using Cox regression analysis, only baseline mitral
      regurgitation >=2+ (HR 1.77, 95% CI 1.05 to 2.99, p=0.03) and systolic pulmonary
      artery pressure (HR 1.15, 95% CI 1.01 to 1.33, p=0.04) were independently
      associated with 1-year mortality, while female gender was protective (HR 0.54,
      95% CI 0.30 to 0.96, p=0.03). CONCLUSIONS: We identified preprocedural
      characteristics associated with 1-year mortality in patients with more-than-mild
      AR after TAVI. More-than-mild baseline mitral regurgitation, higher systolic
      pulmonary artery pressure and male gender were independently associated with
      worse outcome.

PMID- 24895355
TI  - Independent genetic control of maize (Zea mays L.) kernel weight determination
      and its phenotypic plasticity.
AB  - Maize kernel weight (KW) is associated with the duration of the grain-filling
      period (GFD) and the rate of kernel biomass accumulation (KGR). It is also
      related to the dynamics of water and hence is physiologically linked to the
      maximum kernel water content (MWC), kernel desiccation rate (KDR), and moisture
      concentration at physiological maturity (MCPM). This work proposed that
      principles of phenotypic plasticity can help to consolidated the understanding of
      the environmental modulation and genetic control of these traits. For that
      purpose, a maize population of 245 recombinant inbred lines (RILs) was grown
      under different environmental conditions. Trait plasticity was calculated as the
      ratio of the variance of each RIL to the overall phenotypic variance of the
      population of RILs. This work found a hierarchy of plasticities: KDR ~ GFD > MCPM
      > KGR > KW > MWC. There was no phenotypic and genetic correlation between traits
      per se and trait plasticities. MWC, the trait with the lowest plasticity, was the
      exception because common quantitative trait loci were found for the trait and its
      plasticity. Independent genetic control of a trait per se and genetic control of
      its plasticity is a condition for the independent evolution of traits and their
      plasticities. This allows breeders potentially to select for high or low
      plasticity in combination with high or low values of economically relevant
      traits. 

PMID- 24895356
TI  - A theory led narrative review of one-to-one health interventions: the influence
      of attachment style and client-provider relationship on client adherence.
AB  - A theory-led narrative approach was used to unpack the complexities of the
      factors that enable successful client adherence following one-to-one health
      interventions. Understanding this could prepare the provider to anticipate
      different adherence behaviours by clients, allowing them to tailor their
      interventions to increase the likelihood of adherence. The review was done in two
      stages. A theoretical formulation was proposed to explore factors which influence
      the effectiveness of one-to-one interventions to result in client adherence. The
      second stage tested this theory using a narrative synthesis approach. Eleven
      studies across the health care arena were included in the synthesis and explored
      the interplay between client attachment style, client-provider interaction and
      client adherence with health interventions. It emerged that adherence results
      substantially because of the relationship that the client has with the provider,
      which is amplified or diminished by the client's own attachment style. This
      occurs because the client's attachment style shapes how they perceive and behave
      in relationships with the health-care providers, who become the 'secure base'
      from which the client accepts, assimilates and adheres with the recommended
      health intervention. The pathway from one-to-one interventions to adherence is
      explained using moderated mediation and mediated moderation models. 

PMID- 24895357
TI  - Epigenetics of human melanoma: promises and challenges.
AB  - Melanoma is the deadliest form of skin cancer with rising incidence and mortality
      rates. Although early-stage melanoma is highly curable, advanced-stage melanoma
      is refractory to treatment. This underscores the importance of prevention and
      early detection as well as the need to improve treatment and prognostication of
      human melanoma. Elucidating the underlying mechanisms of the initiation and
      progression of human melanoma can help identify potential targets of intervention
      for prevention, diagnosis, therapy, and prognosis of this disease. Aberrant DNA
      methylation and histone modifications are the best-established epigenetic
      mechanisms of carcinogenesis. The occurrence of epigenetic changes prior to
      clinical diagnosis of cancer and their reversibility through
      pharmacologic/genetic approaches offer a promising avenue for basic and
      translational research on human melanoma. Candidate gene(s) or genome-wide
      aberrant DNA methylation and histone modifications have been observed in human
      melanoma tumor tissues and cell lines, and correlated to cellular and functional
      characteristics and/or clinicopathological features of this malignancy. The
      present review summarizes the published researches on aberrant DNA methylation
      and histone modifications in connection with human melanoma. Representative
      studies are highlighted to set forth the current state of knowledge, gaps in the
      knowledgebase, and future directions in these epigenetic fields of research.
      Examples of epigenetic therapy applied for human melanoma in vitro, and the
      challenges of its in vivo application for clinical treatment of solid tumors are
      discussed. 

PMID- 24895359
TI  - Psychosis.

PMID- 24895358
TI  - Early intervention, youth mental health: the value of translational research for
      reform and investment in mental health.

PMID- 24895360
TI  - The first Australian painting of schizophrenia by Ivor Francis.
AB  - OBJECTIVE: This article examines the 1943 surrealistic painting Schizophrenia by
      Ivor Francis, the first major Australian art work depicting a mental disorder.
      Francis was influenced by Max Harris who encouraged him to read works on
      surrealism and psychoanalysis, but took his ideas from the book on schizophrenia
      by the radical Melbourne psychiatrist, Reg Ellery. CONCLUSION: Ivor Francis
      produced a riveting painting that stands as an enduring visual beacon in the
      cultural history of Antipodean psychiatry.

PMID- 24895361
TI  - Vicarious learning for children to be thoughtful, an opportunity not to be missed
      - "Frozen"

PMID- 24895362
TI  - Cestrum Parqui and psychosis.

PMID- 24895363
TI  - Fragmented healthcare for anorexia nervosa.

PMID- 24895364
TI  - Risk management in public mental health.

PMID- 24895367
TI  - Online forum for members launched.

PMID- 24895365
TI  - From the President.

PMID- 24895368
TI  - Review of Faculties, Sections and Special Interest Groups.

PMID- 24895369
TI  - New RANZCP Professional Practice Guideline: Best practice referral, communication
      and shared care arrangements between psychiatrists, general practitioners and
      psychologists.

PMID- 24895371
TI  - The RANZCP Continuing Professional Development program.

PMID- 24895370
TI  - Enhancing community understanding of psychiatry.

PMID- 24895375
TI  - CGRP infusion in unanesthetized rats increases expression of c-Fos in the nucleus
      tractus solitarius and caudal ventrolateral medulla, but not in the trigeminal
      nucleus caudalis.
AB  - BACKGROUND AND AIMS: Calcitonin gene-related peptide (CGRP) and glyceryl
      trinitrate (GTN) infusion in migraineurs provokes headache resembling spontaneous
      migraine, and CGRP receptor antagonists are effective in the treatment of acute
      migraine. We hypothesized that CGRP infusion would increase molecular markers of
      neuronal activation in migraine-relevant tissues of the rat. METHODS: CGRP was
      infused intravenously (i.v.) in freely moving rats to circumvent factors like
      anesthesia, acute surgery and severe hypotension, the three confounding factors
      for c-Fos expression. The trigeminal nucleus caudalis (TNC) was isolated at
      different time points after CGRP infusion. The level of c-Fos mRNA and protein
      expression in TNC were analyzed by qPCR and immunohistochemistry. c-Fos-stained
      nuclei were also counted in the nucleus tractus solitarius (NTS) and caudal
      ventrolateral medulla (CVLM), integrative sites in the brain stem for processing
      cardiovascular signals. We also investigated Zif268 protein expression (another
      immediate early gene) in TNC. The protein expression of p-ERK, p-CREB and c-Fos
      was analyzed in dura mater, trigeminal ganglion (TG) and TNC samples using
      Western blot. RESULTS: CGRP infusion caused a significant dose-dependent fall in
      mean arterial blood pressure. No significant activation of c-Fos in the TNC at
      mRNA and protein levels was observed after CGRP infusion. A significant increase
      in c-Fos protein was observed in the NTS and CVLM in the brain stem. Zif268
      expression in the TNC was also not changed after CGRP infusion. p-ERK was
      increased in the dura mater 30 minutes after CGRP infusion. CONCLUSION: CGRP
      infusion increased the early expression of p-ERK in the dura mater but did not
      increase c-Fos and Zif268 expression in the TNC. The rats may, thus, differ from
      migraine patients, in whom infusion of CGRP caused headache and a delayed
      migraine attack. The rat CGRP infusion model with c-Fos or Zif268 as neuronal
      pain markers in TNC is unsuitable for antimigraine drug testing.

PMID- 24895376
TI  - Functional adrenal insufficiency complicating an overdose of naproxen and
      ibuprofen.

PMID- 24895374
TI  - Tumor microenvironment of metastasis and risk of distant metastasis of breast
      cancer.
AB  - BACKGROUND: Tumor microenvironment of metastasis (TMEM), consisting of direct
      contact between a macrophage, an endothelial cell, and a tumor cell, has been
      associated with metastasis in both rodent mammary tumors and human breast cancer.
      We prospectively examined the association between TMEM score and risk of distant
      metastasis and compared risk associated with TMEM score with that associated with
      IHC4. METHODS: We conducted a case-control study nested within a cohort of 3760
      patients with invasive ductal breast carcinoma diagnosed between 1980 and 2000
      and followed through 2010. Case patients were women who developed a subsequent
      distant metastasis; control subjects were matched (1:1) on age at and calendar
      year of primary diagnosis. TMEM was assessed by triple immunostain and IHC4 by
      standard methods; slides were read by pathologists blinded to outcome. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic
      regression, adjusted for clinical variables. A Receiver Operating Characteristic
      analysis was performed, and the area under the curve was estimated. All
      statistical tests were two-sided. RESULTS: TMEM score was associated with
      increased risk of distant metastasis in estrogen receptor (ER)(+)/human epidermal
      growth factor receptor (HER2)(-) tumors (multivariable OR high vs low tertile =
      2.70; 95% CI = 1.39 to 5.26; P trend = .004), whereas IHC4 score had a borderline
      positive association (OR10 unit increase = 1.06; 95% CI = 1.00 to 1.13); the
      association for TMEM score persisted after adjustment for IHC4 score. The area
      under the curve for TMEM, adjusted for clinical variables, was 0.78. Neither TMEM
      score nor IHC4 score was independently associated with metastatic risk overall or
      in the triple negative or HER2(+) subgroups. CONCLUSIONS: TMEM score predicted
      risk of distant metastasis in ER(+)/HER2(-) breast cancer independently of IHC4
      score and classical clinicopathologic features.

PMID- 24895377
TI  - In-depth proteomics characterization of embryogenesis of the honey bee worker
      (Apis mellifera ligustica).
AB  - Identifying proteome changes of honey bee embryogenesis is of prime importance
      for unraveling the molecular mechanisms that they underlie. However, many
      proteomic changes during the embryonic period are not well characterized. We
      analyzed the proteomic alterations over the complete time course of honey bee
      worker embryogenesis at 24, 48, and 72 h of age, using mass spectrometry-based
      proteomics, label-free quantitation, and bioinformatics. Of the 1460 proteins
      identified the embryo of all three ages, the core proteome (proteins shared by
      the embryos of all three ages, accounting for 40%) was mainly involved in protein
      synthesis, metabolic energy, development, and molecular transporter, which
      indicates their centrality in driving embryogenesis. However, embryos at
      different developmental stages have their own specific proteome and pathway
      signatures to coordinate and modulate developmental events. The young embryos
      (<24 h) stronger expression of proteins related to nutrition storage and nucleic
      acid metabolism may correlate with the cell proliferation occurring at this
      stage. The middle aged embryos (24-48 h) enhanced expression of proteins
      associated with cell cycle control, transporters, antioxidant activity, and the
      cytoskeleton suggest their roles to support rudimentary organogenesis. Among
      these proteins, the biological pathways of aminoacyl-tRNA biosynthesis, beta
      alanine metabolism, and protein export are intensively activated in the embryos
      of middle age. The old embryos (48-72 h) elevated expression of proteins
      implicated in fatty acid metabolism and morphogenesis indicate their
      functionality for the formation and development of organs and dorsal closure, in
      which the biological pathways of fatty acid metabolism and RNA transport are
      highly activated. These findings add novel understanding to the molecular details
      of honey bee embryogenesis, in which the programmed activation of the proteome
      matches with the physiological transition observed during embryogenesis. The
      identified biological pathways and key node proteins allow for further functional
      analysis and genetic manipulation for both the honey bee embryos and other
      eusocial insects. 

PMID- 24895379
TI  - Computing exact p-values for a cross-correlation shotgun proteomics score
      function.
AB  - The core of every protein mass spectrometry analysis pipeline is a function that
      assesses the quality of a match between an observed spectrum and a candidate
      peptide. We describe a procedure for computing exact p-values for the oldest and
      still widely used score function, SEQUEST XCorr. The procedure uses dynamic
      programming to enumerate efficiently the full distribution of scores for all
      possible peptides whose masses are close to that of the spectrum precursor mass.
      Ranking identified spectra by p-value rather than XCorr significantly reduces
      variance because of spectrum-specific effects on the score. In combination with
      the Percolator postprocessor, the XCorr p-value yields more spectrum and peptide
      identifications at a fixed false discovery rate than Mascot, X!Tandem, Comet, and
      MS-GF+ across a variety of data sets. 

PMID- 24895378
TI  - Heterogeneity of pancreatic cancer metastases in a single patient revealed by
      quantitative proteomics.
AB  - Many patients with pancreatic cancer have metastases to distant organs at the
      time of initial presentation. Recent studies examining the evolution of
      pancreatic cancer at the genetic level have shown that clonal complexity of
      metastatic pancreatic cancer is already initiated within primary tumors, and
      organ-specific metastases are derived from different subclones. However, we do
      not yet understand to what extent the evolution of pancreatic cancer contributes
      to proteomic and signaling alterations. We hypothesized that genetic
      heterogeneity of metastatic pancreatic cancer results in heterogeneity at the
      proteome level. To address this, we employed a model system in which cells
      isolated from three sites of metastasis (liver, lung, and peritoneum) from a
      single patient were compared. We used a SILAC-based accurate quantitative
      proteomic strategy combined with high-resolution mass spectrometry to analyze the
      total proteome and tyrosine phosphoproteome of each of the distal metastases. Our
      data revealed distinct patterns of both overall proteome expression and tyrosine
      kinase activities across the three different metastatic lesions. This
      heterogeneity was significant because it led to differential sensitivity of the
      neoplastic cells to small molecule inhibitors targeting various kinases and other
      pathways. For example, R428, a tyrosine kinase inhibitor that targets Axl
      receptor tyrosine kinase, was able to inhibit cells derived from lung and liver
      metastases much more effectively than cells from the peritoneal metastasis.
      Finally, we confirmed that administration of R428 in mice bearing xenografts of
      cells derived from the three different metastatic sites significantly diminished
      tumors formed from liver- and lung-metastasis-derived cell lines as compared with
      tumors derived from the peritoneal metastasis cell line. Overall, our data
      provide proof-of-principle support that personalized therapy of multiple organ
      metastases in a single patient should involve the administration of a combination
      of agents, with each agent targeted to the features of different subclones. 

PMID- 24895381
TI  - Task-specific balance training improves self-assessed function in community
      dwelling older adults with balance deficits and fear of falling: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effects of a 12-week balance training programme on
      self-assessed function and disability in healthy community-dwelling older adults
      with self-perceived balance deficits and fear of falling. DESIGN: A prospective,
      randomized controlled trial. SETTING: Stockholm County, Sweden. PARTICIPANTS: A
      total of 59 community-dwelling older adults (42 women and 17 men) aged 67-93 were
      randomized to either an intervention group (n = 38) or to serve as controls (n =
      21) after baseline testing. INTERVENTION: The intervention was a 12-week, three
      times per week, progressive, specific and individually adjusted group balance
      training programme. MAIN MEASURES: Self-perceived function and disability
      measured with Late Life Function and Disability Instrument. RESULTS: The
      intervention group reported improvement in overall function (p = 0.016), as well
      as in basic (p = 0.044) and advanced lower extremity function (p = 0.025)
      compared with the control group. The study showed no improvement in overall
      disability or upper extremity function. CONCLUSION: This group balance training
      programme improves self-assessed function in community-dwelling older adults with
      balance deficits and fear of falling.

PMID- 24895382
TI  - Comparing the effects of hydrotherapy and land-based therapy on balance in
      patients with Parkinson's disease: a randomized controlled pilot study.
AB  - OBJECTIVE: Our aim was to evaluate the feasibility of a hydrotherapy treatment in
      patients with Parkinson's disease and the effectiveness of this treatment on
      balance parameters in comparison to a traditional land-based physical therapy.
      DESIGN: A randomized single-blind controlled trial. SETTING: Outpatients.
      SUBJECTS: Thirty-four patients with Parkinson's disease in Hoehn-Yahr stage 2.5
      3. INTERVENTION: Group 1 hydrotherapy treatment, group 2 land-based
      rehabilitation treatment. The two groups underwent the same rehabilitation period
      (60 minutes of treatment, five days a week for two months). MAIN MEASURES: The
      primary outcome measures were the centre of the pressure sway area recorded with
      open and closed eyes, using a stabilometric platform. Secondary outcome measures
      were Unified Parkinson's Disease Rating Scale II and III, Timed Up and Go Test,
      Berg Balance Scale, Activities-specific Balance Confidence Scale, Falls Efficacy
      Scale, Falls diary and Parkinson's Disease Questionnaire-39. RESULTS:
      Hydrotherapy treatment proved to be feasible and safe. Patients in both groups
      had a significant improvement in all outcome variables. There was a better
      improvement in patients who underwent hydrotherapy than in patients treated with
      land-based therapy in the centre of pressure sway area closed eyes (mean SD
      change: 45.4 SD64.9 vs. 6.9 SD45.3, p = 0.05), Berg Balance Scale (51.2 SD3.1 vs.
      6.0 SD3.1, p = 0.005), Activities-specific Balance Confidence Scale (16.8 SD10.6
      vs. 4.1 SD5.4, p = 0.0001), Falls Efficacy Scale (-5.9 SD4.8 vs. -1.9 SD1.4, p =
      0.003), Parkinson's Disease Quetionnaire-39 (-18.4 SD12.9 vs. -8.0 SD7.0, p =
      0.006) and falls diary (-2.4 SD2.2 vs. -0.4 SD0.5, p = 0.001). CONCLUSION: Our
      study suggests that hydrotherapy may constitute a possible treatment for balance
      dysfunction in Parkinsonian patients with moderate stage of disease.

PMID- 24895384
TI  - Treatment of choroidal neovascularisation secondary to membranoproliferative
      glomerulonephritis type II with intravitreal ranibizumab.
AB  - Membranoproliferative glomerulonephritis type II (MPGN II) is characterised by
      electron-dense deposits of complement components in the glomerular basement
      membrane and retinal pigment epithelium. Approximately, 10% of affected
      individuals develop serious ocular complications similar to age-related macular
      degeneration such as choroidal neovascularisation (CNV), which has been managed
      with photocoagulation or photodynamic therapy; however, these treatments can
      impact visual acuity. We report the case of a 42-year-old woman with MPGN II
      presenting with decreased visual acuity and paracentral scotoma in her left eye
      due to an extrafoveal choroidal neovascular membrane (growth of new vessels under
      the retina). The patient was successfully treated with intravitreal ranibizumab
      (Lucentis) with restoration of visual function. This case highlights the
      successful management of CNV secondary to MPGN II with the antivascular
      endothelial growth factor agent ranibizumab and emphasises the importance of
      early referral of patients with MPGN II who are reporting of visual 'distortion'.

PMID- 24895383
TI  - Analytical utility of mass spectral binning in proteomic experiments by SPectral
      Immonium Ion Detection (SPIID).
AB  - Unambiguous identification of tandem mass spectra is a cornerstone in mass
      spectrometry-based proteomics. As the study of post-translational modifications
      (PTMs) by means of shotgun proteomics progresses in depth and coverage, the
      ability to correctly identify PTM-bearing peptides is essential, increasing the
      demand for advanced data interpretation. Several PTMs are known to generate
      unique fragment ions during tandem mass spectrometry, the so-called diagnostic
      ions, which unequivocally identify a given mass spectrum as related to a specific
      PTM. Although such ions offer tremendous analytical advantages, algorithms to
      decipher MS/MS spectra for the presence of diagnostic ions in an unbiased manner
      are currently lacking. Here, we present a systematic spectral-pattern-based
      approach for the discovery of diagnostic ions and new fragmentation mechanisms in
      shotgun proteomics datasets. The developed software tool is designed to analyze
      large sets of high-resolution peptide fragmentation spectra independent of the
      fragmentation method, instrument type, or protease employed. To benchmark the
      software tool, we analyzed large higher-energy collisional activation
      dissociation datasets of samples containing phosphorylation, ubiquitylation,
      SUMOylation, formylation, and lysine acetylation. Using the developed software
      tool, we were able to identify known diagnostic ions by comparing histograms of
      modified and unmodified peptide spectra. Because the investigated tandem mass
      spectra data were acquired with high mass accuracy, unambiguous interpretation
      and determination of the chemical composition for the majority of detected
      fragment ions was feasible. Collectively we present a freely available software
      tool that allows for comprehensive and automatic analysis of analogous product
      ions in tandem mass spectra and systematic mapping of fragmentation mechanisms
      related to common amino acids. 

PMID- 24895385
TI  - Vascular ring diagnosis following respiratory arrest.
AB  - Vascular rings can present with non-specific respiratory and/or oesophageal
      symptoms. Early diagnosis requires a high index of suspicion. This case report
      describes an uncommon acute presentation of a vascular ring. We report a thriving
      14-month-old child with a long history of recurrent wheeze and 'noisy breathing'.
      He presented acutely with food bolus impaction in the oesophagus which led to a
      respiratory arrest. Oesophagoscopy and bronchoscopy suggested vascular ring
      anomaly. A contrast-enhanced CT scan demonstrated a right-sided aortic arch with
      left ligamentum arteriosum encircling the oesophagus and airway. The ligament was
      ligated and divided. At follow-up 6 months later, the infant had mild persistent
      stridor but was otherwise well.

PMID- 24895386
TI  - 'A stroke of luck': a case report of a right-sided cerebellar cerebrovascular
      accident in a young man.
AB  - A 27-year-old man with a history of migraines, epilepsy and pulmonary stenosis
      presented to the emergency department with symptoms of vomiting, headache, visual
      disturbance and problems with balance. The team considered the possibility of
      intracranial pathology and an urgent CT head with contrast showed what appeared
      to be a large posterior fossa mass with an appearance suggestive of a primary
      haemangioblastoma, which was causing considerable mass effect. The patient had
      neurosurgery to relieve the obstruction and a biopsy of the area showed the mass
      to be an ischaemic infarct rather than a tumour. Further investigations following
      the stroke confirmed that the cause was due to having antiphospholipid syndrome
      and a patent foramen ovale. The patient made a good recovery following the
      operation and remains well. 

PMID- 24895387
TI  - Acute ischaemic colitis associated with oral phenylephrine decongestant use.
AB  - In this case, the authors have presented for the first time that ischaemic
      colitis may be associated with phenylephrine use. Since phenylephrine is the more
      common active ingredient in over-the-counter (OTC) cold medications, other
      presentations may follow this case. A MEDLINE search was performed for all case
      reports or case series of ischaemic colitis secondary to pseudoephedrine or
      phenylephrine use published between 1966 and 2013. The search resulted in four
      case reports and one case series describing patients with acute onset ischaemic
      colitis with exposure to pseudoephedrine immediately prior to onset. However, we
      found no case reports of ischaemic colitis associated with phenylephrine use. We
      present this case as an unexpected clinical outcome of phenylephrine, which has
      not been associated with ischaemic colitis in the literature. Also, this case
      serves as a reminder of the important clinical lesson to question all patients'
      use of OTC and prescribed medications. 

PMID- 24895380
TI  - Global analysis of S-nitrosylation sites in the wild type (APP) transgenic mouse
      brain-clues for synaptic pathology.
AB  - Alzheimer's disease (AD) is characterized by an early synaptic loss, which
      strongly correlates with the severity of dementia. The pathogenesis and causes of
      characteristic AD symptoms are not fully understood. Defects in various cellular
      cascades were suggested, including the imbalance in production of reactive oxygen
      and nitrogen species. Alterations in S-nitrosylation of several proteins were
      previously demonstrated in various AD animal models and patients. In this work,
      using combined biotin-switch affinity/nano-LC-MS/MS and bioinformatic approaches
      we profiled endogenous S-nitrosylation of brain synaptosomal proteins from wild
      type and transgenic mice overexpressing mutated human Amyloid Precursor Protein
      (hAPP). Our data suggest involvement of S-nitrosylation in the regulation of 138
      synaptic proteins, including MAGUK, CamkII, or synaptotagmins. Thirty-eight
      proteins were differentially S-nitrosylated in hAPP mice only. Ninety-five S
      nitrosylated peptides were identified for the first time (40% of total, including
      33 peptides exclusively in hAPP synaptosomes). We verified differential S
      nitrosylation of 10 (26% of all identified) synaptosomal proteins from hAPP mice,
      by Western blotting with specific antibodies. Functional enrichment analysis
      linked S-nitrosylated proteins to various cellular pathways, including:
      glycolysis, gluconeogenesis, calcium homeostasis, ion, and vesicle transport,
      suggesting a basic role of this post-translational modification in the regulation
      of synapses. The linkage of SNO-proteins to axonal guidance and other processes
      related to APP metabolism exclusively in the hAPP brain, implicates S
      nitrosylation in the pathogenesis of Alzheimer's disease. 

PMID- 24895388
TI  - Lesser trochanter fracture: the presenting feature of a more sinister pathology.
AB  - We report the rare case of a 75-year-old man who was hospitalised following
      referral by his general practitioner with a 4-day history of worsening groin
      pain. Initial radiographs demonstrated an isolated avulsion fracture of the
      lesser trochanter. There were associated bony changes indicating pathological
      bone disease, likely secondary to bony metastasis. Further investigation revealed
      a renal mass almost certainly consistent with a renal cell carcinoma. This case
      emphasises the importance of having a high index of suspicion for neoplastic
      pathology when low impact injuries result in fractures. 

PMID- 24895389
TI  - Doomed tongue twisters.

PMID- 24895390
TI  - Acute spontaneous atraumatic bilateral anterior dislocation of the shoulder joint
      with Hill-Sachs lesions: first reported case and review of literature.
AB  - The anatomy of the shoulder joint comprises a relatively large humeral head with
      a shallow glenoid cavity allowing a remarkable range of motion at the expense of
      inherent instability. Despite anterior shoulder dislocations being the most
      common type encountered, bilateral dislocations are rare and almost always
      posterior. The aetiology is usually direct or indirect trauma related to sports,
      seizures, electric shock or electroconvulsive therapy. We present the first
      reported case of atraumatic bilateral acute anterior shoulder dislocations with
      associated Hill-Sachs lesions in a young, fit and well patient with no
      comorbidities. MRI illustrated the Hill-Sachs lesions with superior labral tear
      from anterior to posterior, and confirmed the acute nature of the injury by
      demonstrating the bone marrow oedema. The patient was treated surgically with
      arthroscopic anterior stabilisation. At 6 months following surgery, the patient
      has a pain free full range of movement of both shoulders with no further
      dislocations and has returned to work. 

PMID- 24895391
TI  - Refractory nausea and vomiting in the setting of well-controlled idiopathic
      intracranial hypertension.
AB  - Summary A 27-year-old woman with a history of recurrent nausea and vomiting in
      the setting of idiopathic intracranial hypertension (IIH) was admitted for
      control of unremitting nausea and vomiting. Initial antiemetic therapy included
      optimisation of IIH therapy by titrating acetazolamide, in addition to using
      ondansetron and metoclopramide as needed, with minimal relief. She was ultimately
      treated with palonosetron with complete resolution of her acute nausea. Nausea,
      often treated with 5-hydroxytryptamine (5-HT3) receptor antagonists, approved for
      perioperative and chemotherapy-induced nausea, are used off-label to treat nausea
      and vomiting outside of those settings. The efficacy of different regimens has
      been compared in the literature and continues to remain controversial. When
      choosing from different 5-HT3 antagonists there are other considerations, in
      addition to efficacy to consider: dosing schedule, half-life, time of onset,
      duration and cost-to-benefit ratio, and although one 5-HT3 antagonist may not
      have been effective, another one may be. In our case palonosetron, with a
      significantly longer half-life than other 5-HT3 antagonists, was effective in
      resolving nausea when compared with the more commonly used ondansetron. 

PMID- 24895392
TI  - Surgery and radiation therapy for brain metastases from classic biphasic
      pulmonary blastoma.
AB  - Pulmonary blastoma, a rare malignant lung tumour, can metastasise to the brain.
      However, there is no evidence for any effective treatment. The aim of this report
      is to discuss the treatment options for pulmonary blastoma and confirm the
      necessity for a pathological diagnosis. A 75-year-old man was admitted with
      progressive right-sided hemiplegia and aphasia. MRI showed multiple brain
      tumours. A left frontal lobe lesion was surgically resected, after which he
      underwent whole brain radiation (30 Gy/10 fractions). He died of an acute
      exacerbation of interstitial pneumonia. On performing autopsy, partial responses
      in the brain metastases that had been irradiated were confirmed pathologically.
      Thus, we present pathological confirmation that surgery and radiation therapy
      have therapeutic effects on brain metastases from pulmonary blastoma. 

PMID- 24895393
TI  - Acute onset of bilateral visual loss during sildenafil therapy in a young infant
      with congenital heart disease.
AB  - We report a case of posterior non-arteritic ischaemic optic neuropathy (NAION)
      causing bilateral visual loss in a 7-month-old female infant, after a therapeutic
      course with sildenafil, a phosphodiesterase type 5 inhibitors (PDE5i). The
      patient was affected by a complex cyanotic congenital heart defect and had
      undergone cavopulmonary anastomosis (Glenn operation) 3 months ago. After 2
      months of recurring chylothorax, a course of oral sildenafil was administered,
      with the hypothesis that pulmonary vascular resistances were increased.
      Approximately 4 weeks later the acute onset of visual worsening and poor
      pupillary light reflex prompted the diagnosis of posterior NAION. Despite a rapid
      cessation of PDE5i and systemic treatment with corticosteroids, no visual
      recovery was noticed at 2-year follow-up. NAION has been associated with PDE5i
      therapy in adults, but to the best of our knowledge it is almost unheard of in
      children. We suggest close monitoring of visual function in children undergoing
      treatment with sildenafil. 

PMID- 24895395
TI  - Shunting to relieve the pressures of graduate school...literally.

PMID- 24895394
TI  - An incidental finding of a nodal recurrence of cutaneous malignant melanoma after
      a 45-year disease-free period.
AB  - We report the case of an 84-year-old woman who had a nodal recurrence of melanoma
      45 years after the primary diagnosis of an extremity cutaneous melanoma. It is
      believed to be the longest disease-free latency period reported between primary
      melanoma diagnosis and recurrence to date. Late recurrences of melanoma are rare
      and recurrence after four decades extremely rare. This article suggests melanoma
      is a disease with a potentially lifelong risk of recurrence and thus clinicians
      and patients must be vigilant and aware of this risk, particularly if late
      recurrences are to be recognised early and management optimised. 

PMID- 24895396
TI  - Breathless after bypass.
AB  - A 65-year-old normotensive, non-athletic man presented to the cardiology clinic
      with exertional dyspnoea and chest discomfort. Echocardiography revealed mild
      left ventricular hypertrophy with good systolic function but with regional wall
      motion abnormalities suggesting ischaemia. Coronary angiography showed
      significant three-vessel disease. He underwent coronary artery bypass surgery,
      which was complicated by recurrent pericardial and pleural effusions, requiring a
      pericardial window procedure. Over the following year he became increasingly
      oedematous and breathless. On ECG the complexes were low voltage with impaired R
      wave progression and atrial fibrillation. Echocardiography revealed progression
      of the left ventricular hypertrophy (LVH) with a bright myocardium and
      restrictive filling pattern. MRI scanning confirmed the diagnosis of cardiac
      amyloidosis. He was referred for transplant but was considered unsuitable due to
      extensive mediastinal scarring. This case demonstrates the importance of a high
      index of suspicion for amyloidosis, especially in patients with unexplained LVH.
      Cardiac MRI or biopsy may expedite the diagnosis. 

PMID- 24895397
TI  - Acute focal bacterial nephritis.

PMID- 24895398
TI  - Severe lactic acidosis and multiorgan failure due to thiamine deficiency during
      total parenteral nutrition.
AB  - A 16-year-old perioperative paediatric patient presented with refractory lactic
      acidosis and multiorgan failure due to thiamine-deficient total parenteral
      nutrition during a recent national multivitamin shortage. Urgent empiric
      administration of intravenous thiamine resulted in prompt recovery from this life
      threatening condition. Despite readily available treatment, a high index of
      suspicion is required to prevent cardiovascular collapse and mortality. 

PMID- 24895399
TI  - Choosing sides--asymmetric centriole and basal body assembly.
AB  - Centrioles and basal bodies (CBBs) are microtubule-rich cylindrical structures
      that nucleate and organize centrosomes and cilia, respectively. Despite their
      apparent ninefold rotational symmetry, the nine sets of triplet microtubules in
      CBBs possess asymmetries in their morphology and in the structures that associate
      with them. These asymmetries define the position of nascent CBB assembly, the
      orientation of ciliary beating, the orientation of spindle poles and the
      maintenance of cellular geometry. For some of these functions, the orientation of
      CBBs is first established during new CBB biogenesis when the daughter structure
      is positioned adjacent to the mother. The mother CBB organizes the surrounding
      environment that nascent CBBs are born into, thereby providing a nest for the new
      CBB to develop. Protists, including ciliates and algae, highlight the importance
      of this environment with the formation of asymmetrically placed scaffolds onto
      which new basal bodies assemble and are positioned. Recent studies illuminate the
      positioning of nascent centrioles relative to a modular pericentriolar material
      (PCM) environment and suggest that, like ciliates, centrosomes organize an
      immediate environment surrounding centrioles for their biogenesis and
      positioning. In this Commentary, I will explore the positioning of nascent CBB
      assembly as the first event in building cellular asymmetries and describe how the
      environment surrounding both basal bodies and centrioles may define asymmetric
      assembly. 

PMID- 24895401
TI  - Stepwise and cooperative assembly of a cytokinetic core complex in Saccharomyces
      cerevisiae.
AB  - Actomyosin ring (AMR) contraction and the synthesis of an extracellular septum
      are interdependent pathways that mediate cytokinesis in the yeast Saccharomyces
      cerevisiae and other eukaryotes. How these interdependent pathways are physically
      connected is central for understanding cytokinesis. The yeast IQGAP (Iqg1p)
      belongs to the conserved AMR. The F-BAR-domain-containing protein Hof1p is a
      member of a complex that stimulates cell wall synthesis. We report here on the
      stepwise formation of a physical connection between both proteins. The C-terminal
      IQ-repeats of Iqg1p first bind to the essential myosin light chain before both
      proteins assemble with Hof1p into the Mlc1p-Iqg1p-Hof1p (MIH) bridge. Mutations
      in Iqg1p that disrupt the MIH complex alter Hof1p targeting to the AMR and impair
      AMR contraction. Epistasis analyses of two IQG1 alleles that are incompatible
      with formation of the MIH complex support the existence and functional
      significance of a large cytokinetic core complex. We propose that the MIH complex
      acts as hinge between the AMR and the proteins involved in cell wall synthesis
      and membrane attachment. 

PMID- 24895403
TI  - Extracellular cleavage of E-cadherin promotes epithelial cell extrusion.
AB  - Epithelial cell extrusion and subsequent apoptosis is a key mechanism to prevent
      the accumulation of excess cells. By contrast, when driven by oncogene
      expression, apical cell extrusion is followed by proliferation and represents an
      initial step of tumorigenesis. E-cadherin (E-cad), the main component of adherens
      junctions, has been shown to be essential for epithelial cell extrusion, but its
      mechanistic contribution remains unclear. Here, we provide clear evidence that
      cell extrusion can be driven by the cleavage of E-cad, both in a wild-type and an
      oncogenic environment. We first show that CDC42 activation in a single epithelial
      cell results in its efficient matrix metalloproteinase (MMP)-sensitive extrusion
      through MEK signalling activation and this is supported by E-cad cleavage.
      Second, using an engineered cleavable form of E-cad, we demonstrate that, by
      itself, truncation of extracellular E-cad at the plasma membrane promotes apical
      extrusion. We propose that extracellular cleavage of E-cad generates a rapid
      change in cell-cell adhesion that is sufficient to drive apical cell extrusion.
      Whereas in normal epithelia, extrusion is followed by apoptosis, when combined
      with active oncogenic signalling, it is coupled to cell proliferation. 

PMID- 24895400
TI  - Extracellular deposition of matrilin-2 controls the timing of the myogenic
      program during muscle regeneration.
AB  - Here, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein
      in controlling the early stages of myogenic differentiation. We observed Matn2
      deposition around proliferating, differentiating and fusing myoblasts in culture
      and during muscle regeneration in vivo. Silencing of Matn2 delayed the expression
      of the Cdk inhibitor p21 and of the myogenic genes Nfix, MyoD and Myog,
      explaining the retarded cell cycle exit and myoblast differentiation. Rescue of
      Matn2 expression restored differentiation and the expression of p21 and of the
      myogenic genes. TGF-beta1 inhibited myogenic differentiation at least in part by
      repressing Matn2 expression, which inhibited the onset of a positive-feedback
      loop whereby Matn2 and Nfix activate the expression of one another and activate
      myoblast differentiation. In vivo, myoblast cell cycle arrest and muscle
      regeneration was delayed in Matn2(-/-) relative to wild-type mice. The expression
      levels of Trf3 and myogenic genes were robustly reduced in Matn2(-/-) fetal limbs
      and in differentiating primary myoblast cultures, establishing Matn2 as a key
      modulator of the regulatory cascade that initiates terminal myogenic
      differentiation. Our data thus identify Matn2 as a crucial component of a genetic
      switch that modulates the onset of tissue repair. 

PMID- 24895404
TI  - Genetic diversity of hepatitis B virus and hepatitis C virus in human
      immunodeficiency virus type 1-co-infected patients from Venezuela.
AB  - The aim of this study was to evaluate the prevalence and genetic diversity of
      hepatitis B virus (HBV) and hepatitis C virus (HCV) in human immunodeficiency
      virus type 1 (HIV-1)-co-infected Venezuelan patients. The prevalence of HBV and
      HCV markers of infection in HIV-1 patients was 14% for anti-hepatitis B core
      antigen, 3% for hepatitis B surface antigen and 0.7% for anti-HCV, respectively.
      HBV prevalence was higher than HCV, as expected for a country where sexual
      intercourse, not intravenous drug use, is the main mode of HIV-1 transmission.
      The HCV genotype distribution in HIV-1-co-infected patients was similar to that
      obtained in HCV-mono-infected patients, but genotype 1a was more frequent in HIV
      1-infected patients. The HBV genotype distribution exhibited differences between
      mono-infected and HIV-1-co-infected individuals. HBV F3 was the most common
      subgenotype in both groups, followed by F1b in HIV-1 co-infection and F2 in HBV
      mono-infection. In addition, genotype G (single infection) was found in an HIV-1
      co-infected individual. A high prevalence of occult HBV infection was detected in
      HIV-1-co-infected naive patients (18%), with F2 being the most common genotype
      (75%). To the best of our knowledge, these results correspond to the first
      description of frequency and molecular characterization of HBV and HCV in HIV-1
      Venezuelan patients.

PMID- 24895402
TI  - Transport along the dendritic endoplasmic reticulum mediates the trafficking of
      GABAB receptors.
AB  - In neurons, secretory organelles within the cell body are complemented by the
      dendritic endoplasmic reticulum (ER) and Golgi outposts (GOPs), whose role in
      neurotransmitter receptor trafficking is poorly understood. gamma-aminobutyric
      acid (GABA) type B metabotropic receptors (GABABRs) regulate the efficacy of
      synaptic transmission throughout the brain. Their plasma membrane availability is
      controlled by mechanisms involving an ER retention motif and assembly-dependent
      ER export. Thus, they constitute an ideal molecular model to study ER
      trafficking, but the extent to which the dendritic ER participates in GABABR
      biosynthesis has not been thoroughly explored. Here, we show that GABAB1
      localizes preferentially to the ER in dendrites and moves long distances within
      this compartment. Not only diffusion but also microtubule and dynein-dependent
      mechanisms control dendritic ER transport. GABABRs insert throughout the
      somatodendritic plasma membrane but dendritic post-ER carriers containing GABABRs
      do not fuse selectively with GOPs. This study furthers our understanding of the
      spatial selectivity of neurotransmitter receptors for dendritic organelles. 

PMID- 24895405
TI  - Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in
      keratoconus.
AB  - Keratoconus, a common inherited ocular disorder resulting in progressive corneal
      thinning, is the leading indication for corneal transplantation in the developed
      world. Genome-wide association studies have identified common SNPs 100 kb
      upstream of ZNF469 strongly associated with corneal thickness. Homozygous
      mutations in ZNF469 and PR domain-containing protein 5 (PRDM5) genes result in
      brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal
      recessive generalized connective tissue disorder associated with extreme corneal
      thinning and a high risk of corneal rupture. Some individuals with heterozygous
      PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly
      reduced corneal thickness, keratoconus and blue sclera. We hypothesized that
      heterozygous variants in PRDM5 and ZNF469 predispose to the development of
      isolated keratoconus. We found a significant enrichment of potentially pathologic
      heterozygous alleles in ZNF469 associated with the development of keratoconus (P
      = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare
      potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients
      represents a significant mutational load and highlights ZNF469 as the most
      significant genetic factor responsible for keratoconus identified to date. 

PMID- 24895406
TI  - The chaperone-like protein 14-3-3eta interacts with human alpha-synuclein
      aggregation intermediates rerouting the amyloidogenic pathway and reducing alpha
      synuclein cellular toxicity.
AB  - Familial and idiopathic Parkinson's disease (PD) is associated with the abnormal
      neuronal accumulation of alpha-synuclein (aS) leading to beta-sheet-rich
      aggregates called Lewy Bodies (LBs). Moreover, single point mutation in aS gene
      and gene multiplication lead to autosomal dominant forms of PD. A connection
      between PD and the 14-3-3 chaperone-like proteins was recently proposed, based on
      the fact that some of the 14-3-3 isoforms can interact with genetic PD-associated
      proteins such as parkin, LRRK2 and aS and were found as components of LBs in
      human PD. In particular, a direct interaction between 14-3-3eta and aS was
      reported when probed by co-immunoprecipitation from cell models, from
      parkinsonian brains and by surface plasmon resonance in vitro. However, the
      mechanisms through which 14-3-3eta and aS interact in PD brains remain unclear.
      Herein, we show that while 14-3-3eta is unable to bind monomeric aS, it interacts
      with aS oligomers which occur during the early stages of aS aggregation. This
      interaction diverts the aggregation process even when 14-3-3eta is present in sub
      stoichiometric amounts relative to aS. When aS level is overwhelmingly higher
      than that of 14-3-3eta, the fibrillation process becomes a sequestration
      mechanism for 14-3-3eta, undermining all processes governed by this protein.
      Using a panel of complementary techniques, we single out the stage of aggregation
      at which the aS/14-3-3eta interaction occurs, characterize the products of the
      resulting processes, and show how the processes elucidated in vitro are relevant
      in cell models. Our findings constitute a first step in elucidating the molecular
      mechanism of aS/14-3-3eta interaction and in understanding the critical
      aggregation step at which 14-3-3eta has the potential to rescue aS-induced
      cellular toxicity. 

PMID- 24895408
TI  - Role of OVCA1/DPH1 in craniofacial abnormalities of Miller-Dieker syndrome.
AB  - OVCA1/DPH1 (OVCA1) encodes a component of the diphthamide biosynthesis pathway
      and is located on chromosome 17p13.3. Deletions in this region are associated
      with Miller-Dieker syndrome (MDS). Ovca1/Dph1 (Ovca1)-null mice exhibit multiple
      developmental defects, including cleft palate, growth restriction and perinatal
      lethality, suggesting a role in the craniofacial abnormalities associated with
      MDS. Conditional ablation of Ovca1 in neural crest cells, but not in cranial
      paraxial mesoderm, also results in cleft palate and shortened lower jaw
      phenotypes, similar to Ovca1-null embryos. Expression of transgenic myc-tagged
      Ovca1 in craniofacial structures can partially rescue the cleft palate and
      shortened mandible of Ovca1-null embryos. Interestingly, Ovca1-null mutants are
      resistant to conditional expression of diphtheria toxin subunit A in both neural
      crest cell and paraxial mesoderm derivatives. However, OVCA1-dependent
      diphthamide biosynthesis is essential for neural crest cell-derived craniofacial
      development but that is dispensable for paraxial mesodermal-derived craniofacial
      structures in mammals. These findings suggest that OVCA1 deficiency in the neural
      crest contributes to the craniofacial abnormalities in patients with MDS. Also,
      our findings provide new insights into the molecular and cellular mechanisms that
      lead to the craniofacial defects of MDS. 

PMID- 24895410
TI  - The first report of a Chinese family with McLeod syndrome.
AB  - We report the first case of a Chinese family with McLeod syndrome (MLS). The two
      affected brothers show significant phenotypic heterogeneity. The index case has
      peripheral acanthocytosis, choreoathetosis of his feet, a slowly progressive
      neuropathy and myopathy, and an elevated serum creatine kinase (CK) level. His
      elder brother has more prominent chorea of the shoulders, epilepsy, a rapidly
      progressive neuropathy and normal serum CK. The diagnosis of MLS was confirmed by
      a genetic test which showed a hemizygous frameshift mutation in the XK gene. 

PMID- 24895407
TI  - Peroxidasin is essential for eye development in the mouse.
AB  - Mutations in Peroxidasin (PXDN) cause severe inherited eye disorders in humans,
      such as congenital cataract, corneal opacity and developmental glaucoma. The role
      of peroxidasin during eye development is poorly understood. Here, we describe the
      first Pxdn mouse mutant which was induced by ENU (N-ethyl-N-nitrosourea) and led
      to a recessive phenotype. Sequence analysis of cDNA revealed a T3816A mutation
      resulting in a premature stop codon (Cys1272X) in the peroxidase domain. This
      mutation causes severe anterior segment dysgenesis and microphthalmia resembling
      the manifestations in patients with PXDN mutations. The proliferation and
      differentiation of the lens is disrupted in association with aberrant expression
      of transcription factor genes (Pax6 and Foxe3) in mutant eyes. Additionally, Pxdn
      is involved in the consolidation of the basement membrane and lens epithelium
      adhesion in the ocular lens. Lens material including gamma-crystallin is extruded
      into the anterior and posterior chamber due to local loss of structural integrity
      of the lens capsule as a secondary damage to the anterior segment development
      leading to congenital ocular inflammation. Moreover, Pxdn mutants exhibited an
      early-onset glaucoma and progressive retinal dysgenesis. Transcriptome profiling
      revealed that peroxidasin affects the transcription of developmental and eye
      disease-related genes at early eye development. These findings suggest that
      peroxidasin is necessary for cell proliferation and differentiation and for
      basement membrane consolidation during eye development. Our studies provide
      pathogenic mechanisms of PXDN mutation-induced congenital eye diseases. 

PMID- 24895411
TI  - Not only for egg yolk--functional and evolutionary insights from expression,
      selection, and structural analyses of Formica ant vitellogenins.
AB  - Vitellogenin (Vg), a storage protein, has been extensively studied for its egg
      yolk precursor role, and it has been suggested to be fundamentally involved in
      caste differences in social insects. More than one Vg copy has been reported in
      several oviparous species, including ants. However, the number and function of
      different Vgs, their phylogenetic relatedness, and their role in reproductive
      queens and nonreproductive workers have been studied in few species only. We
      studied caste-biased expression of Vgs in seven Formica ant species. Only one
      copy of conventional Vg was identified in Formica species, and three Vg homologs,
      derived from ancient duplications, which represent yet undiscovered Vg-like
      genes. We show that each of these Vg-like genes is present in all studied
      Hymenoptera and some of them in other insects as well. We show that after each
      major duplication event, at least one of the Vg-like genes has experienced a
      period of positive selection. This, combined with the observation that the Vg
      like genes have acquired or lost specific protein domains suggests sub- or
      neofunctionalization between Vg and the duplicated genes. In contrast to earlier
      studies, Vg was not consistently queen biased in its expression, and the caste
      bias of the three Vg-like genes was highly variable among species. Furthermore, a
      truncated and Hymenoptera-specific Vg-like gene, Vg-like-C, was consistently
      worker biased. Multispecies comparisons are essential for Vg expression studies,
      and for gene expression studies in general, as we show that expression and also,
      putative functions cannot be generalized even among closely related species. 

PMID- 24895409
TI  - Post-GWAS gene-environment interplay in breast cancer: results from the Breast
      and Prostate Cancer Cohort Consortium and a meta-analysis on 79,000 women.
AB  - We studied the interplay between 39 breast cancer (BC) risk SNPs and established
      BC risk (body mass index, height, age at menarche, parity, age at menopause,
      smoking, alcohol and family history of BC) and prognostic factors (TNM stage,
      tumor grade, tumor size, age at diagnosis, estrogen receptor status and
      progesterone receptor status) as joint determinants of BC risk. We used a nested
      case-control design within the National Cancer Institute's Breast and Prostate
      Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We
      performed stratified analyses for both the risk and prognostic factors, testing
      for heterogeneity for the risk factors, and case-case comparisons for
      differential associations of polymorphisms by subgroups of the prognostic
      factors. We analyzed multiplicative interactions between the SNPs and the risk
      factors. Finally, we also performed a meta-analysis of the interaction ORs from
      BPC3 and the Breast Cancer Association Consortium. After correction for multiple
      testing, no significant interaction between the SNPs and the established risk
      factors in the BPC3 study was found. The meta-analysis showed a suggestive
      interaction between smoking status and SLC4A7-rs4973768 (Pinteraction = 8.84 *
      10(-4)) which, although not significant after considering multiple comparison,
      has a plausible biological explanation. In conclusion, in this study of up to
      almost 79 000 women we can conclusively exclude any novel major interactions
      between genome-wide association studies hits and the epidemiologic risk factors
      taken into consideration, but we propose a suggestive interaction between smoking
      status and SLC4A7-rs4973768 that if further replicated could help our
      understanding in the etiology of BC. 

PMID- 24895412
TI  - TIMP-1 via TWIST1 induces EMT phenotypes in human breast epithelial cells.
AB  - Tissue inhibitor of metalloproteinase-1 (TIMP-1) regulates intracellular
      signaling networks for inhibition of apoptosis. Tetraspanin (CD63), a cell
      surface binding partner for TIMP-1, was previously shown to regulate integrin
      mediated survival pathways in the human breast epithelial cell line MCF10A. In
      the current study, we show that TIMP-1 expression induces phenotypic changes in
      cell morphology, cell adhesion, cytoskeletal remodeling, and motility, indicative
      of an epithelial-mesenchymal transition (EMT). This is evidenced by loss of the
      epithelial cell adhesion molecule E-cadherin with an increase in the mesenchymal
      markers vimentin, N-cadherin, and fibronectin. Signaling through TIMP-1, but not
      TIMP-2, induces the expression of TWIST1, an important EMT transcription factor
      known to suppress E-cadherin transcription, in a CD63-dependent manner. RNAi
      mediated knockdown of TWIST1 rescued E-cadherin expression in TIMP-1
      overexpressing cells, demonstrating a functional significance of TWIST1 in TIMP-1
      mediated EMT. Furthermore, analysis of TIMP-1 structural mutants reveals that
      TIMP-1 interactions with CD63 that activate cell survival signaling and EMT do
      not require the matrix metalloproteinase (MMP)-inhibitory domain of TIMP-1. Taken
      together, these data demonstrate that TIMP-1 binding to CD63 activates
      intracellular signal transduction pathways, resulting in EMT-like changes in
      breast epithelial cells, independent of its MMP-inhibitory function.
      IMPLICATIONS: TIMP-1's function as an endogenous inhibitor of MMP or as a
      "cytokine-like" signaling molecule may be a critical determinant for tumor cell
      behavior.

PMID- 24895413
TI  - Plasma adipokines and risk of hepatocellular carcinoma in chronic hepatitis B
      virus-infected carriers: a prospective study in taiwan.
AB  - BACKGROUND: Obesity is considered a risk factor for hepatocellular carcinoma
      (HCC). The relationship between adipocytokine and HCC in hepatitis B virus (HBV)
      carriers remains unclear. We prospectively investigated the association of
      adiponectin, leptin, and visfatin levels with HCC. METHODS: We conducted a nested
      case-control study in a community-based cohort with 187 incident HCC and 374 HCC
      free HBV carriers. Unconditional logistic regression was conducted to estimate
      the ORs and 95% confidence intervals (CI). RESULTS: Adiponectin, but not leptin
      and visfatin, levels were associated with an increased risk of HCC after
      adjustment for other metabolic factors and HBV-related factors. The risk was
      increased [OR = 0.51; 95% CI, 0.12-2.11; OR = 4.88 (1.46-16.3); OR = 3.79 (1.10
      13.0); OR = 4.13 (1.13-15.1) with each additional quintiles, respectively] with a
      significant dose-response trend (P(trend) = 0.003). HCC risk associated with
      higher adiponectin level was higher in HBV carriers with ultrasonographic fatty
      liver, genotype C infection, higher viral load, and with elevated alanine
      aminotransferase. Longitudinally, participants with higher adiponectin were less
      likely to achieve surface antigen of hepatitis B virus (HBsAg) seroclearance and
      more likely to have persistently higher HBV DNA. Eventually, they were more
      likely to develop liver cirrhosis [OR = 1.65 (0.62-4.39); OR = 3.85 (1.47-10.1);
      OR = 2.56 (0.96-6.84); OR = 3.76 (1.33-10.7) for the second, third, fourth, and
      fifth quintiles, respectively; P(trend) = 0.017] before HCC. CONCLUSIONS:
      Elevated adiponectin levels were independently associated with an increased risk
      of HCC. IMPACT: Adiponectin may play different roles in the virus-induced and
      metabolic-related liver diseases, but the underlying mechanism remains unknown.

PMID- 24895414
TI  - Risk prediction models for melanoma: a systematic review.
AB  - Melanoma incidence is increasing rapidly worldwide among white-skinned
      populations. Earlier diagnosis is the principal factor that can improve
      prognosis. Defining high-risk populations using risk prediction models may help
      targeted screening and early detection approaches. In this systematic review, we
      searched Medline, EMBASE, and the Cochrane Library for primary research studies
      reporting or validating models to predict risk of developing cutaneous melanoma.
      A total of 4,141 articles were identified from the literature search and six
      through citation searching. Twenty-five risk models were included. Between them,
      the models considered 144 possible risk factors, including 18 measures of number
      of nevi and 26 of sun/UV exposure. Those most frequently included in final risk
      models were number of nevi, presence of freckles, history of sunburn, hair color,
      and skin color. Despite the different factors included and different cutoff
      values for sensitivity and specificity, almost all models yielded sensitivities
      and specificities that fit along a summary ROC with area under the ROC (AUROC) of
      0.755, suggesting that most models had similar discrimination. Only two models
      have been validated in separate populations and both also showed good
      discrimination with AUROC values of 0.79 (0.70-0.86) and 0.70 (0.64-0.77).
      Further research should focus on validating existing models rather than
      developing new ones.

PMID- 24895415
TI  - Gpr1 is an active chemerin receptor influencing glucose homeostasis in obese
      mice.
AB  - Chemerin is an adipose-derived signaling protein (adipokine) that regulates
      adipocyte differentiation and function, immune function, metabolism, and glucose
      homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second
      chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin
      with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is
      essentially unknown. Herein, we report that expression of murine Gpr1 mRNA is
      high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle.
      In contrast to chemerin (Rarres2) and Cmklr1, Gpr1 expression predominates in the
      non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygous Gpr1
      knockout mice fed on a high-fat diet developed more severe glucose intolerance
      than WT mice despite having no difference in body weight, adiposity, or energy
      expenditure. Moreover, mice lacking Gpr1 exhibited reduced glucose-stimulated
      insulin levels and elevated glucose levels in a pyruvate tolerance test. This
      study is the first, to our knowledge, to report the effects of Gpr1 deficiency on
      adiposity, energy balance, and glucose homeostasis in vivo. Moreover, these novel
      results demonstrate that GPR1 is an active chemerin receptor that contributes to
      the regulation of glucose homeostasis during obesity. 

PMID- 24895416
TI  - Preconditioning actions of aldosterone through p38 signaling modulation in
      isolated rat hearts.
AB  - Although persistent excessive actions of aldosterone have unfavorable effects on
      the cardiovascular system, primarily via mineralocorticoid receptor (MR)
      dependent pathways, the pathophysiological significance of aldosterone cascade
      activation in heart diseases has not yet been fully clarified. We herein examined
      the effects of short-term aldosterone stimulation at a physiological dose on
      cardiac function during ischemia-reperfusion injury (IRI). In order to study the
      effects of aldosterone preconditioning, male Wistar rat Langendorff hearts were
      perfused with 10(-9) mol/l of aldosterone for 10 min before ischemia, and the
      response to IRI was assessed. Although aldosterone did not affect the baseline
      hemodynamic parameters, preconditioning actions of aldosterone significantly
      improved the recovery in left ventricular contractility and left ventricular end
      diastolic pressure associated with a reduced activity of creatine phosphokinase
      released into the perfusate after ischemia-reperfusion. Notably, the MR inhibitor
      eplerenone did not abrogate these beneficial effects. Biochemical analyses
      revealed that p38MAPK phosphorylation was significantly increased during
      aldosterone preconditioning before ischemia, whereas its phosphorylation was
      substantially attenuated during sustained ischemia-reperfusion, compared with the
      results for in the non-preconditioned control hearts. This dual regulation of
      p38MAPK was not affected by eplerenone. The phosphorylation levels of other MAPKs
      were not altered by aldosterone preconditioning. In conclusion, the temporal
      induction of the aldosterone cascade, at a physiological dose, has favorable
      effects on cardiac functional recovery and injury following ischemia-reperfusion
      in a MR-independent manner. Phasic dynamism of p38MAPK activation may play a key
      role in the physiological compensatory pathway of aldosterone under severe
      cardiac pathological conditions. 

PMID- 24895419
TI  - PIL1 participates in a negative feedback loop that regulates its own gene
      expression in response to shade.

PMID- 24895420
TI  - Mammalian cell-transforming potential of traffic-linked ultrafine particulate
      matter PM0.056 in urban roadside atmosphere.
AB  - We examined the clastogenic and cell-transforming potential of ultrafine
      particulate matter fraction PM0.056 of urban ambient aerosol using mammalian
      cells. PM1.0, PM0.56 and PM0.056 fractions were sampled from roadside atmosphere
      of an urban area using the cascade impactor MOUDI-NR-110. The potential to induce
      cytotoxicity, DNA damage and micronuclei formation was examined at the test
      concentrations of 3, 6, 12.5, 25, 50 and 100 MUg/ml using the 3-4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay, the plasmid relaxation assay and the
      C3H10T1/2 (10T1/2) cells. The cell-transforming potential was investigated in
      vitro using 10T1/2 cell transformation assay and the soft agar assay. PM1, PM0.56
      and PM0.056 fractions were found to be toxic in dose-dependent manner. These
      induced cytotoxicity at five test concentrations, the ultrafine particle fraction
      PM0.056 showed greater cytotoxic potential. PM0.056 induced micronucleus
      formation in 10T1/2 cells. The effect was statistically significant. The DNA
      damaging potential was measured in a plasmid relaxation assay. Both fine and
      ultrafine particle fraction PM0.56 and PM0.056 displayed greater effect as
      compared to larger PM1 fraction. DNA damage was found to be dependent on
      particulate matter intrinsic pro-oxidant chemicals. The ability of the ultrafine
      particle fraction PM0.056 to induce morphological cell transformation was
      demonstrated by significant and dose-dependent increases in type III focus
      formation by morphologically transformed cells in culture flasks and their clonal
      expansion in soft agar. It is concluded that the traffic-linked ultrafine
      particle fraction PM0.056 in the atmosphere by the roadside of an urban area is
      clastogenic and able to induce morphological transformation of mammalian cells. 

PMID- 24895421
TI  - Effects of Continuous Irrigation During Burring on Thermal Necrosis and Fusion
      Strength in a Rabbit Arthrodesis Model.
AB  - BACKGROUND: High-speed burring used to prepare bony surfaces during arthrodesis
      procedures can increase heat generation that may impede healing and fusion.
      Irrigation during burring has the potential to improve early healing of burred
      bone surfaces and result in a stronger fusion mass. The purpose of this study was
      to determine the effects of continuous irrigation during burring on thermal
      necrosis and fusion strength in an in vivo arthrodesis animal model. METHODS: A
      small joint rabbit ulnohumeral arthrodesis model was developed and utilized in 16
      New Zealand white rabbits. Joints were prepared and contoured using a high-speed
      cutting burr and fixed in compression with crossed screws to obtain fusion.
      Prepared bony surfaces were either irrigated (n = 8) with chilled 6 degrees C (43
      degrees F) saline or not irrigated (n = 8). Specimens were harvested,
      radiographed, mechanically tested for torque to failure and stiffness, and
      evaluated for histology. RESULTS: Fusion rate was 100% (8/8) when joints were
      irrigated during burring and 75% (6/8) when joints were not irrigated (P = .45).
      Mechanical testing showed a mean torque to failure of 0.85 Nm and 0.72 Nm in
      irrigated and nonirrigated specimens, respectively (P = .57). Histology showed
      evidence of less mature osseous formation in nonirrigated specimens compared to
      irrigated specimens. CONCLUSION: There was an overall trend toward decreased
      fusion rate and lower fusion mass strength in nonirrigated fusion specimens
      compared with those treated with chilled irrigation during bone preparation.
      CLINICAL RELEVANCE: Continuous chilled irrigation during bone preparation with
      burring may have a positive effect on fusion rate and fusion mass strength for
      arthrodesis procedures.

PMID- 24895422
TI  - New species of Paramoebidium (trichomycetes, Mesomycetozoea) from the
      Mediterranean, with comments about the amoeboid cells in Amoebidiales.
AB  - Paramoebidium, along with Amoebidium, constitute the order Amoebidiales,
      traditionally included in the ecological group trichomycetes and conventionally
      studied by mycologists, although they are phylogenetically embedded in the
      protist clade Mesomycetozoean (Ichthyosporea). The genus Paramoebidium has 13
      accepted species, all associated with immature stages of aquatic insects. Three
      new species of Paramoebidium, P. angulatum, P. avitruviense and P. ecdyonuridaei,
      are described here, associated with either Plecoptera and Ephemeroptera nymphs.
      During routine observations of the amoeboid phases, uroidal adhesive filaments at
      the posterior end of the amoebae were noted and photographed, this being a novel
      observation for the Amoebidiales. This and other features are illustrated for all
      taxa. 

PMID- 24895417
TI  - Effects of genetics and in utero diet on murine pancreatic development.
AB  - Intrauterine (IU) malnutrition could alter pancreatic development. In this study,
      we describe the effects of high-fat diet (HFD) during pregnancy on fetal growth
      and pancreatic morphology in an 'at risk' animal model of metabolic disease, the
      glucose transporter 4 (GLUT4) heterozygous mouse (G4+/-). WT female mice mated
      with G4+/- males were fed HFD or control diet (CD) for 2 weeks before mating and
      throughout pregnancy. At embryonic day 18.5, fetuses were killed and pancreata
      isolated for analysis of morphology and expression of genes involved in insulin
      (INS) cell development, proliferation, apoptosis, glucose transport and function.
      Compared with WT CD, WT HFD fetal pancreata had a 2.4-fold increase in the number
      of glucagon (GLU) cells (P=0.023). HFD also increased GLU cell size by 18% in WT
      pancreata compared with WT CD. Compared with WT CD, G4+/- CD had an increased
      number of INS cells and decreased INS and GLU cell size. Compared with G4+/- CD,
      G4+/- HFD fetuses had increased pancreatic gene expression of Igf2, a mitogen and
      inhibitor of apoptosis. The expression of genes involved in proliferation,
      apoptosis, glucose transport, and INS secretion was not altered in WT HFD
      compared with G4+/- HFD pancreata. In contrast to WT HFD pancreata, HFD exposure
      did not alter pancreatic islet morphology in fetuses with GLUT4
      haploinsufficiency; this may be mediated in part by increased Igf2 expression.
      Thus, interactions between IU diet and fetal genetics may play a critical role in
      the developmental origins of health and disease. 

PMID- 24895423
TI  - Ambrosiella roeperi sp. nov. is the mycangial symbiont of the granulate ambrosia
      beetle, Xylosandrus crassiusculus.
AB  - Isolations from the granulate ambrosia beetle, Xylosandrus crassiusculus
      (Coleoptera: Curculionidae: Scolytinae: Xyleborini), collected in Georgia, South
      Carolina, Missouri and Ohio, yielded an undescribed species of Ambrosiella in
      thousands of colony-forming units (CFU) per individual female. Partial sequences
      of ITS and 28S rDNA regions distinguished this species from other Ambrosiella
      spp., which are asexual symbionts of ambrosia beetles and closely related to
      Ceratocystis spp. Ambrosiella roeperi sp. nov. produces sporodochia of branching
      conidiophores with disarticulating swollen cells, and the branches are terminated
      by thick-walled aleurioconidia, similar to the conidiophores and aleurioconidia
      of A. xylebori, which is the mycangial symbiont of a related ambrosia beetle, X.
      compactus. Microscopic examinations found homogeneous masses of arthrospore-like
      cells growing in the mycangium of X. crassiusculus, without evidence of other
      microbial growth. Using fungal-specific primers, only the ITS rDNA region of A.
      roeperi was amplified and sequenced from DNA extractions of mycangial contents,
      suggesting that it is the primary or only mycangial symbiont of this beetle in
      USA. 

PMID- 24895424
TI  - SNP markers identify widely distributed clonal lineages of Phytophthora
      colocasiae in Vietnam, Hawaii and Hainan Island, China.
AB  - Taro (Colocasia esculenta) is an important food crop, and taro leaf blight caused
      by Phytophthora colocasiae can significantly affect production. Our objectives
      were to develop single nucleotide polymorphism (SNP) markers for P. colocasiae
      and characterize populations in Hawaii (HI), Vietnam (VN) and Hainan Island,
      China (HIC). In total, 379 isolates were analyzed for mating type and multilocus
      SNP profiles including 214 from HI, 97 from VN and 68 from HIC. A total of 1152
      single nucleotide variant (SNV) sites were identified via restriction site
      associated DNA (RAD) sequencing of two field isolates. Genotyping with 27 SNPs
      revealed 41 multilocus SNP genotypes grouped into seven clonal lineages
      containing 2-232 members. Three clonal lineages were shared among countries. In
      addition, five SNP markers had a low incidence of loss of heterozygosity (LOH)
      during asexual laboratory growth. For HI and VN, >95% of isolates were the A2
      mating type. On HIC, isolates within single clonal lineages had A1, A2 and A0
      (neuter) isolates. The implications for the wide dispersal of clonal lineages are
      discussed. 

PMID- 24895425
TI  - Transposable elements belonging to the Tc1-Mariner superfamily are heavily
      mutated in Colletotrichum graminicola.
AB  - Transposable elements are ubiquitous and constitute an important source of
      genetic variation in addition to generating deleterious mutations. Several
      filamentous fungi are able to defend against transposable elements using
      RIP(repeat-induced point mutation)-like mechanisms, which induce mutations in
      duplicated sequences. The sequenced Colletotrichum graminicola genome and the
      availability of transposable element databases provide an efficient approach for
      identifying and characterizing transposable elements in this fungus, which was
      the subject of this study. We identified 132 full-sized Tc1-Mariner transposable
      elements in the sequenced C. graminicola genome, which were divided into six
      families. Several putative transposases that have been found in these elements
      have conserved DDE motifs, but all are interrupted by stop codons. An in silico
      analysis showed evidence for RIP-generated mutations. The TCg1 element, which was
      cloned from the Brazilian 2908 m isolate, has a putative transposase sequence
      with three characteristic conserved motifs. However, this sequence is interrupted
      by five stop codons. Genomic DNA from various isolates was analyzed by
      hybridization with an internal region of TCg1. All of the isolates featured
      transposable elements that were similar to TCg1, and several hybridization
      profiles were identified. C. graminicola has many Tc1-Mariner transposable
      elements that have been degenerated by characteristic RIP mutations. It is
      unlikely that any of the characterized elements are autonomous in the sequenced
      isolate. The possible existence of active copies in field isolates from Brazil
      was shown. The TCg1 element is present in several C. graminicola isolates and is
      a potentially useful molecular marker for population studies of this
      phytopathogen. 

PMID- 24895426
TI  - Relationships between Swiss needle cast and ectomycorrhizal fungus diversity.
AB  - Swiss needle cast (SNC) is a disease specific to Douglas-fir (Pseudotsuga
      menziesii) caused by the ascomycete Phaeocryptopus gaeumannii. Here we examine
      characteristics of the EM fungus community that are potentially useful in
      predictive models that would monitor forest health. We found that mean EM density
      (number of colonized root tips/soil core) varied nearly 10-fold among sites of
      varying levels of SNC, while mean EM fungus species richness (number of
      species/soil core) varied by about 2.5 times. Strong relationships were found
      between EM and SNC parameters: EM species richness was positively correlated with
      both Douglas-fir needle retention (R(2) = 0.93) and EM density (R(2) = 0.65); EM
      density also was significantly correlated with Douglas-fir needle retention (R(2)
      = 0.70). These simple characteristics of the EM fungus community could be used to
      monitor forest health and generate predictive models of site suitability for
      Douglas-fir. Based on previous findings that normally common EM types were
      reduced in frequency on sites with severe SNC, we also hypothesized that some EM
      fungi would be stress tolerant-dominant species. Instead, we found that various
      fungi were able to form EM with the stressed trees, but none were consistently
      dominant across samples in the severely diseased areas. 

PMID- 24895427
TI  - Hypothesized evolutionary trends in zoospore ultrastructural characters in
      Chytridiales (Chytridiomycota).
AB  - Chytridiales is an order of zoosporic fungi currently comprising species
      representing 19 genera. Although morphologically and genetically diverse, these
      taxa have in common a zoospore with a suite of ultrastructural characters unique
      among Chytridiomycota. However, multiple states have been reported for almost
      every character that defines the Chytridiales zoospore. Two zoospore types have
      been recognized, each corresponding to a family. Here we examine zoospore
      ultrastructure of 52 isolates in Chytridiales and assess states for six
      characters to hypothesize evolutionary trends, using parsimony ancestral state
      reconstruction for evolutionary analysis. Based on suites of character states, we
      describe four additional zoospore types in Chytridiales. Five of the six
      characters ([i] location of the nucleus, [ii] morphology of the kinetosome
      associated structure, [iii] complexity of the microtubular root, [iv] microbody
      lipid globule complex cisterna structure and [v] thickness of the flagellar plug)
      revealed ancestral and derived states. The sixth character, structure of the
      paracrystalline inclusion, did not resolve ancestral and derived states. In each
      of the lineages within Chytridiales, the evolutionary trend appears to have been
      from a more complex zoospore to a less complex zoospore with reduced features. As
      we isolate and analyze additional taxa, we discover new ultrastructural character
      states that assist in taxon delineation and phylogenetic interpretation. 

PMID- 24895428
TI  - Two new species of Lactarius associated with Alnus acuminata subsp. arguta in
      Mexico.
AB  - In pure stands of Alnus acuminata subsp. arguta trees from Sierra Norte de Puebla
      (central Mexico) two undescribed ectomycorrhizal species of Lactarius were
      discovered. Distinction of the two new species is based on morphological
      characters and supported with phylogenetic analyses of the nuclear ribosomal DNA
      ITS region and part of the gene that encodes for the second largest subunit of
      RNA polymerase II (rpb2). The phylogenies inferred recovered the two species in
      different clades strongly supported by posterior probabilities and bootstrap
      values. The new Lactarius species are recognized as part of the assemblage of
      ectomycorrhizal fungi associated with Alnus acuminata. Information about these
      taxa includes the morphological variation achieved along 16 monitories 2010-2013.
      Descriptions are provided. They are accompanied by photos including SEM
      photomicrographs of basidiospores and information on differences between them and
      other related taxa from Europe and the United States. 

PMID- 24895430
TI  - Farnesol induces apoptosis-like cell death in the pathogenic fungus Aspergillus
      flavus.
AB  - Farnesol (FOH) is known to induce apoptosis in some fungi and mammalian cells. We
      treated Aspergillus flavus, one of the leading causes of human invasive
      aspergillosis and a key producer of the most potent naturally occurring
      hepatocarcinogenic compounds, with FOH to assess its effect on the viability of
      the fungus. FOH strongly inhibited germination and growth of A. flavus and
      induced markers for apoptosis including nuclear condensation, phosphatidylserine
      (PS) externalization, DNA fragmentation and intracellular reactive oxygen species
      (ROS) generation, metacaspase activation and abnormal cellular ultrastructure.
      Moreover, FOH-induced apoptosis in A. flavus was inhibited by the broad-spectrum
      caspase inhibitor Z-VAD-fmk and partially inhibited by the ROS scavenger l
      proline, which suggests that FOH induces apoptosis in A. flavus via a mechanism
      involving metacaspase activation and ROS production. 

PMID- 24895429
TI  - Alessioporus and Pulchroboletus (Boletaceae, Boletineae), two novel genera for
      Xerocomus ichnusanus and X. roseoalbidus from the European Mediterranean basin:
      molecular and morphological evidence.
AB  - Alessioporus and Pulchroboletus are proposed as new monotypic genera to
      accommodate the thermo-xerophilic European species Xerocomus ichnusanus and X.
      roseoalbidus respectively. The present research focused on both morphological
      features and multigene molecular phylogeny (nrITS, nrLSU, tef-1alpha datasets) to
      elucidate the taxonomic status of these two rare Mediterranean boletes and
      delineate a natural classification within the family Boletaceae. Macro- and
      microscopic descriptions of the two species based on inclusive taxon sampling are
      provided and supported by line drawings of the main anatomical features.
      Phylogenetic relationships, ecology, geographical distribution and delimitation
      from the most closely allied taxa also are highlighted. In addition, epitype
      specimens are selected for both species. 

PMID- 24895431
TI  - New Porcini (Boletus sect. Boletus) from Australia and Thailand.
AB  - Boletus albobrunnescens and B. austroedulis are described as new species in
      section Boletus from Thailand and Australia respectively. The former is easily
      characterized by the pure white basidiomata that stain brown. Boletus
      austroedulis has a gray-brown, slightly rugulose pileus with hymeniform
      pileipellis producing pileocystidia, and the stipe is only apically reticulate if
      at all. These new species represent ancient lineages inferred from prior
      molecular phylogenetic analyses. 

PMID- 24895432
TI  - CFM-ID: a web server for annotation, spectrum prediction and metabolite
      identification from tandem mass spectra.
AB  - CFM-ID is a web server supporting three tasks associated with the interpretation
      of tandem mass spectra (MS/MS) for the purpose of automated metabolite
      identification: annotation of the peaks in a spectrum for a known chemical
      structure; prediction of spectra for a given chemical structure and putative
      metabolite identification--a predicted ranking of possible candidate structures
      for a target spectrum. The algorithms used for these tasks are based on
      Competitive Fragmentation Modeling (CFM), a recently introduced probabilistic
      generative model for the MS/MS fragmentation process that uses machine learning
      techniques to learn its parameters from data. These algorithms have been
      extensively tested on multiple datasets and have been shown to out-perform
      existing methods such as MetFrag and FingerId. This web server provides a simple
      interface for using these algorithms and a graphical display of the resulting
      annotations, spectra and structures. CFM-ID is made freely available at
      http://cfmid.wishartlab.com.

PMID- 24895433
TI  - Uncoupling of the dynamics of host-pathogen interaction uncovers new mechanisms
      of viral interferon antagonism at the single-cell level.
AB  - Antiviral defence in mammals is mediated through type-I interferons (IFNs).
      Viruses antagonise this process through expression of IFN antagonist proteins
      (IAPs). Understanding and modelling of viral escape mechanisms and the dynamics
      of IAP action has the potential to facilitate the development of specific and
      safe drugs. Here, we describe the dynamics of interference by selected viral
      IAPs, NS1 from Influenza A virus and NS3/4A from Hepatitis C virus. We used Tet
      inducible IAP gene expression to uncouple this process from virus-driven
      dynamics. Stochastic activation of the IFN-beta gene required the use of single
      cell live imaging to define the efficacy of the inhibitors during the virus
      induced signalling processes. We found significant correlation between the onset
      of IAP expression and halted IFN-beta expression in cells where IFN-beta
      induction had already occurred. These data indicate that IAPs not only prevent
      antiviral signalling prior to IFN-beta induction, but can also stop the antiviral
      response even after it has been activated. We found reduced NF-kappaB activation
      to be the underlying mechanism by which activated IFN expression can be blocked.
      This work demonstrates a new mechanism by which viruses can antagonise the IFN
      response. 

PMID- 24895434
TI  - Structure of 5-hydroxymethylcytosine-specific restriction enzyme, AbaSI, in
      complex with DNA.
AB  - AbaSI, a member of the PvuRts1I-family of modification-dependent restriction
      endonucleases, cleaves deoxyribonucleic acid (DNA) containing 5
      hydroxymethylctosine (5hmC) and glucosylated 5hmC (g5hmC), but not DNA containing
      unmodified cytosine. AbaSI has been used as a tool for mapping the genomic
      locations of 5hmC, an important epigenetic modification in the DNA of higher
      organisms. Here we report the crystal structures of AbaSI in the presence and
      absence of DNA. These structures provide considerable, although incomplete,
      insight into how this enzyme acts. AbaSI appears to be mainly a homodimer in
      solution, but interacts with DNA in our structures as a homotetramer. Each AbaSI
      subunit comprises an N-terminal, Vsr-like, cleavage domain containing a single
      catalytic site, and a C-terminal, SRA-like, 5hmC-binding domain. Two N-terminal
      helices mediate most of the homodimer interface. Dimerization brings together the
      two catalytic sites required for double-strand cleavage, and separates the 5hmC
      binding-domains by ~70 A, consistent with the known activity of AbaSI which
      cleaves DNA optimally between symmetrically modified cytosines ~22 bp apart. The
      eukaryotic SET and RING-associated (SRA) domains bind to DNA containing 5
      methylcytosine (5mC) in the hemi-methylated CpG sequence. They make contacts in
      both the major and minor DNA grooves, and flip the modified cytosine out of the
      helix into a conserved binding pocket. In contrast, the SRA-like domain of AbaSI,
      which has no sequence specificity, contacts only the minor DNA groove, and in our
      current structures the 5hmC remains intra-helical. A conserved, binding pocket is
      nevertheless present in this domain, suitable for accommodating 5hmC and g5hmC.
      We consider it likely, therefore, that base-flipping is part of the recognition
      and cleavage mechanism of AbaSI, but that our structures represent an earlier,
      pre-flipped stage, prior to actual recognition. 

PMID- 24895436
TI  - DiseaseConnect: a comprehensive web server for mechanism-based disease-disease
      connections.
AB  - The DiseaseConnect (http://disease-connect.org) is a web server for analysis and
      visualization of a comprehensive knowledge on mechanism-based disease
      connectivity. The traditional disease classification system groups diseases with
      similar clinical symptoms and phenotypic traits. Thus, diseases with entirely
      different pathologies could be grouped together, leading to a similar treatment
      design. Such problems could be avoided if diseases were classified based on their
      molecular mechanisms. Connecting diseases with similar pathological mechanisms
      could inspire novel strategies on the effective repositioning of existing drugs
      and therapies. Although there have been several studies attempting to generate
      disease connectivity networks, they have not yet utilized the enormous and
      rapidly growing public repositories of disease-related omics data and literature,
      two primary resources capable of providing insights into disease connections at
      an unprecedented level of detail. Our DiseaseConnect, the first public web
      server, integrates comprehensive omics and literature data, including a large
      amount of gene expression data, Genome-Wide Association Studies catalog, and text
      mined knowledge, to discover disease-disease connectivity via common molecular
      mechanisms. Moreover, the clinical comorbidity data and a comprehensive
      compilation of known drug-disease relationships are additionally utilized for
      advancing the understanding of the disease landscape and for facilitating the
      mechanism-based development of new drug treatments. 

PMID- 24895438
TI  - More light shed on light chains.

PMID- 24895435
TI  - The combination of transcriptomics and informatics identifies pathways targeted
      by miR-204 during neurogenesis and axon guidance.
AB  - Vertebrate organogenesis is critically sensitive to gene dosage and even subtle
      variations in the expression levels of key genes may result in a variety of
      tissue anomalies. MicroRNAs (miRNAs) are fundamental regulators of gene
      expression and their role in vertebrate tissue patterning is just beginning to be
      elucidated. To gain further insight into this issue, we analysed the
      transcriptomic consequences of manipulating the expression of miR-204 in the
      Medaka fish model system. We used RNA-Seq and an innovative bioinformatics
      approach, which combines conventional differential expression analysis with the
      behavior expected by miR-204 targets after its overexpression and knockdown. With
      this approach combined with a correlative analysis of the putative targets, we
      identified a wider set of miR-204 target genes belonging to different pathways.
      Together, these approaches confirmed that miR-204 has a key role in eye
      development and further highlighted its putative function in neural
      differentiation processes, including axon guidance as supported by in vivo
      functional studies. Together, our results demonstrate the advantage of
      integrating next-generation sequencing and bioinformatics approaches to
      investigate miRNA biology and provide new important information on the role of
      miRNAs in the control of axon guidance and more broadly in nervous system
      development. 

PMID- 24895439
TI  - How many Achilles' heels does a podocyte have? An update on podocyte biology.

PMID- 24895437
TI  - Inflammatory stress reduces the effectiveness of statins in the kidney by
      disrupting HMGCoA reductase feedback regulation.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are unlikely to gain the
      same benefit from conventional doses of statins as do patients with
      cardiovascular disease alone. This study investigated whether inflammation
      accompanying CKD causes statin resistance. METHODS: Inflammatory stress was
      induced by adding cytokines and lipopolysaccharide (LPS) to human mesangial cells
      (HMCs) in vitro, and in vivo by subcutaneous casein injection in apolipoprotein
      E, scavenger receptors class A and CD36 triple knockout mice. RESULTS:
      Inflammatory stress exacerbated cholesterol accumulation and was accompanied in
      vitro and in vivo by increased HMGCoA reductase (HMGCoA-R) mRNA and protein
      expression mediated via activation of the sterol regulatory element-binding
      protein cleavage-activating protein (SCAP)/sterol regulatory element-binding
      protein 2 pathway. Atorvastatin reduced HMGCoA-R enzymatic activity and
      intracellular cholesterol synthesis in vitro; however, inflammatory stress
      weakened these suppressive effects. Atorvastatin at concentrations of 15 uM
      inhibited HMGCoA-R activity by 50% (IC50) in HMCs, but the same concentration in
      the presence of interleukin (IL)-1beta resulted in only 30% inhibition of HMGCoA
      R activity in HMCs. Knocking down SCAP prevented statin resistance induced by IL
      1beta, and overexpression of SCAP-induced statin resistance even without
      inflammatory stress. In vivo, the amount of atorvastatin required to lower serum
      cholesterol and decrease kidney lipid accumulation rose from 2 to 10 mg/kg/day in
      the presence of inflammatory stress. CONCLUSIONS: Inflammatory stress can disrupt
      HMGCoA-R-mediated cholesterol synthesis resulting in intracellular lipid
      accumulation and statin resistance.

PMID- 24895442
TI  - Yes, minority and underserved populations will participate in biospecimen
      collection.

PMID- 24895440
TI  - Risk of death following kidney allograft failure: a systematic review and meta
      analysis of cohort studies.
AB  - BACKGROUND: People with kidney allograft failure represent an increasing fraction
      of all those starting dialysis therapy. We sought to summarize prognosis
      following kidney allograft failure and identify potentially beneficial
      interventions or modifiable risk factors. METHODS: We searched MEDLINE and EMBASE
      (inception to 1 October 2013) and article reference lists without language
      restriction and selected cohort studies of all-cause mortality and fatal
      infection-related and cardiovascular events in people starting dialysis following
      kidney allograft failure. Two reviewers independently extracted data on study
      design, participant characteristics, dialysis modality, transplant nephrectomy,
      immunosuppression strategy, transplant-naive comparators and risk of bias.
      Discrepancies were resolved with a third reviewer. RESULTS: Forty studies
      comprising 249 716 participants met the inclusion criteria. The first year of
      dialysis therapy was associated with the highest mortality. By random effects
      meta-analysis, annual risk of death, from years 1 to 4, was 0.12 [95% confidence
      interval (95% CI): 0.09-0.15], 0.06 (95% CI: 0.05-0.07), 0.05 (95% CI: 0.04-0.06)
      and 0.05 (95% CI: 0.04-0.06), respectively. We found high heterogeneity in each
      meta-analysis, which remained unexplained by prespecified subgroup analyses. We
      could not find sufficient information to summarize the risk for fatal infection
      related and cardiovascular events, or to test the role of transplant nephrectomy
      or different immunosuppressive strategies. Risk of bias was high, especially
      participation bias. CONCLUSION: Mortality is higher during the first year of
      dialysis treatment following kidney allograft failure than in subsequent years.
      Insufficient data are available to assess factors or interventions potentially
      impacting prognosis following kidney allograft failure. In a culture promoting
      transplantation, clinical research of different models of care in this growing
      high-risk population should be a research priority.

PMID- 24895443
TI  - Predictors of the occurrence of smoking discontinuation in novice adolescent
      smokers.
AB  - BACKGROUND: While long-term cessation is an outcome of interest in adult smokers,
      little is known about discontinuing smoking in adolescent smokers. The objective
      was to identify the predictors of the occurrence of smoking discontinuation in
      novice smokers. METHODS: Data were available for 620 adolescent smokers
      participating in a longitudinal study on the natural course of nicotine
      dependence. Data on smoking discontinuation (i.e., stopping smoking for >=12
      consecutive months) were collected in 20 cycles over five years from grade 7 to
      11 (1999-2005). Data on 37 potential predictors representing a wide range of
      demographic, psychosocial, health, lifestyle, smoking-related, and context
      related characteristics were collected once, 2 to 3 times, or 20 times. Pooled
      logistic regression was used to test the association between each potential
      predictor and smoking discontinuation, adjusting for potential confounders.
      RESULTS: Forty percent of 620 participants discontinued smoking during follow up.
      Male sex [OR (95% confidence interval), 1.8 (1.3-2.4)], age [1.3 (1.1-1.5)],
      cigarette package warnings [0.6 (0.5-0.9)], team sports participation [1.4 (1.1
      1.9)], family stress [0.7 (0.6-1.0)], worrying about weight [0.6 (0.5-0.9)],
      overweight [0.7 (0.5-1.0)], illicit drugs use [0.5 (0.4-0.7)], tolerance [0.6
      (0.4-1.0)], and other nicotine dependence symptoms [1.0 (0.9-1.0)] were
      statistically significantly associated with smoking discontinuation. CONCLUSIONS:
      Both individual and context-level factors were associated with smoking
      discontinuation. IMPACT: Programs and policy targeting novice adolescent smokers
      may be more effective if factors associated with long-term smoking
      discontinuation are taken into consideration. In particular, young smokers may
      need help with dependence symptoms, body weight issues, family functioning, and
      polysubstance use. Cigarette package warnings may be effective in helping
      adolescents discontinue smoking. Cancer Epidemiol Biomarkers Prev; 23(6); 1090
      101. (c)2014 AACR.

PMID- 24895444
TI  - In memoriam: an appreciation for the NCI R25T cancer education and career
      development program.
AB  - On September 7, 2013, the NCI R25T award mechanism ended its final
      "receipt/review/award cycle" after more than two decades shaping the cancer
      prevention and control workforce. Created in 1991 to respond to a national
      shortage of cancer prevention and control researchers, the R25T supported
      innovative institutional programs with specialized curricula preparing
      individuals for careers as independent scientists for the field. Required
      elements ensured developing transdisciplinary sensibilities and skills highly
      suited to team science, including conducting collaborative research with mentors
      of complementary expertise. R25Ts provided trainee stipends, research, education,
      and travel funds at levels far higher than T32 National Service Research Awards
      to attract individuals from diverse disciplines. Graduates are faculty at all
      academic ranks, and hold leadership positions such as associate directors of
      cancer prevention and control. Beyond its trainees, R25Ts also recruited into the
      field other students exposed through courses in specialized prevention curricula,
      as well as course instructors and trainee mentors, who did not initially consider
      their work to be relevant to cancer prevention. Although advances are being
      achieved, prevention efforts are not yet fully realized, and currently unknown is
      the impact on the workforce of terminating the R25T, including whether it is
      another barrier to preventing cancer.

PMID- 24895445
TI  - Simplified procedure of silymarin extraction from Silybum marianum L. Gaertner.
AB  - Silymarin, a mixture of flavonolignans exhibiting many pharmacological
      activities, is obtained from the fruits of milk thistle (Silybum marianum L.
      Gaertner). Due to the high lipid content in thistle fruits, the European
      Pharmacopoeia recommends a two-step process of its extraction. First, the fruits
      are defatted for 6 h, using n-hexane; second, silymarin is extracted with
      methanol for 5 more hours. The presented data show that this extremely long
      traditional Soxhlet extraction process can be shortened to a few minutes using
      pressurized liquid extraction (PLE). PLE also allows to eliminate the defatting
      stage required in the traditional procedure, thus simplifying the silymarin
      extraction procedure and preventing silymarin loss caused by defatting. The PLE
      recoveries obtained under the optimized extraction conditions are clearly better
      than the ones obtained by the Pharmacopoeia-recommended Soxhlet extraction
      procedure. The PLE yields of silychristin, silydianin, silybin A, silybin B,
      isosilybin A and isosilybin B in acetone are 3.3, 6.9, 3.3, 5.1, 2.6 and 1.5 mg/g
      of the non-defatted fruits, respectively. The 5-h Soxhlet extraction with
      methanol on defatted fruits gives only ~72% of the silymarin amount obtained in
      10 min PLE at 125 degrees C. 

PMID- 24895446
TI  - A method for analysis of wilfordmine in human plasma by liquid chromatography
      coupled with ion trap mass spectrometry.
AB  - A simple and rapid liquid chromatography-ion trap mass spectrometric (LC-IT/MS)
      method has been developed and validated for quantification of wilfordmine in
      human plasma. After the protein precipitation was carried out by acetonitrile and
      the solution was cleaned by solid-phase extraction, the chromatographic
      separation was performed on a Zorbax Plus RRHD C18 column by using a mixture of
      acetonitrile and 10.0 mmol/L ammonium acetate solution (70:30, v/v) as the mobile
      phase at a flow rate of 0.7 mL/min. Detection was performed on an atmospheric
      pressure chemical ionization source in the positive multiple reaction monitoring
      mode using aconitine as an internal standard (IS) with transitions of m/z 806
      >710 for wilfordmine, and 646->586 for IS, respectively. The obtained calibration
      curve was linear (r = 0.9992) over the concentration range of 0.5-100.0 MUg/L
      with a lower limit of quantification of 0.5 MUg/L in plasma. The intra- and
      interday relative standard deviations were <7.0 and 12.3%, respectively. The
      recoveries were between 86.0 and 97.0%. The proposed method was found to be
      applicable to clinical studies. 

PMID- 24895447
TI  - Long-term safety of an everolimus-eluting bioresorbable vascular scaffold and the
      cobalt-chromium XIENCE V stent in a porcine coronary artery model.
AB  - BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold
      (Absorb) has shown promising clinical results; however, only limited preclinical
      data have been published. We sought to investigate detailed pathological
      responses to the Absorb versus XIENCE V (XV) in a porcine coronary model with
      duration of implant extending from 1 to 42 months. METHODS AND RESULTS: A total
      of 335 devices (263 Absorb and 72 XV) were implanted in 2 or 3 main coronary
      arteries of 136 nonatherosclerotic swine and examined by light microscopy,
      scanning electron microscopy, pharmacokinetics, and gel permeation chromatography
      analyses at various time points. Vascular responses to Absorb and XV were largely
      comparable at all time points, with struts being sequestered within the
      neointima. Inflammation was mild to moderate (with absence of inflammation at 1
      month) for both devices, although the scores were greater in Absorb at 6 to 36
      months. Percent area stenosis was significantly greater in Absorb than XV at all
      time points except at 3 months. The extent of fibrin deposition was similar
      between Absorb and XV, which peaked at 1 month and decreased rapidly thereafter.
      Histomorphometry showed expansile remodeling of Absorb-implanted arteries
      starting after 12 months, and lumen area was significantly greater in Absorb than
      XV at 36 and 42 months. These changes correlated with dismantling of Absorb seen
      after 12 months. Gel permeation chromatography analysis confirmed that
      degradation of Absorb was complete by 36 months. CONCLUSIONS: Absorb demonstrates
      comparable long-term safety to XV in porcine coronary arteries with mild to
      moderate inflammation. Although Absorb was associated with greater percent
      stenosis relative to XV, expansile remodeling was observed after 12 months in
      Absorb with significantly greater lumen area at >= 36 months. Resorption is
      considered complete at 36 months.

PMID- 24895448
TI  - Acute changes of mitral valve geometry during interventional edge-to-edge repair
      with the MitraClip system are associated with midterm outcomes in patients with
      functional valve disease: preliminary results from a prospective single-center
      study.
AB  - BACKGROUND: Transcatheter mitral valve repair (TMVR) is a treatment option in
      patients with symptomatic functional or degenerative mitral regurgitation (DMR)
      at high surgical risk. The acute effect of MitraClip procedure on mitral valve
      (MV) annular geometry and its relation to functional outcomes is unclear. We
      sought to assess immediate effect of TMVR on MV annular geometry with 3
      dimensional (3D) transesophageal echocardiography and the association of MV
      diameter reduction with functional response after 6 months. METHODS AND RESULTS:
      Consecutive patients (n = 111; age, 78.3 +/- 8.1 years) at high surgical risk
      (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation],
      29.8+/-21.5%) underwent TMVR. The procedure was completed successfully in 107
      (96%) patients with 3D reconstruction of MV annular geometry immediately before
      and after clip implantation. Only patients with functional mitral regurgitation
      (n = 71) experienced an acute reduction of anterior-posterior MV diameters (4.0
      +/- 0.6 and 3.6 +/- 0.6 cm; P < 0.0001), MV annulus areas (2D annulus area, 13.9
      +/- 3.8 and 12.8 +/- 3.4 cm(2); P < 0.0001 and 3D annulus area, 14.4 +/- 3.9 and
      12.9 +/- 3.4 cm(2); P < 0.0001), and MV annular geometry (MV sphericity index,
      0.9 +/- 0.1 and 0.8 +/- 0.1; P < 0.0001); the lateral medial MV diameters
      remained unchanged (4.3 +/- 0.7 and 4.4 +/- 0.6 cm; P = 0.13). In subjects with
      DMR, all MV annular geometry-defining values were not significantly altered after
      TMVR (n = 36; P > 0.05). Acute anterior-posterior diameter reduction was
      associated with clinical response to TMVR after 6 months of follow-up (cutoff
      value, >= 6.4%; area under the curve, 0.81; P = 0.002; sensitivity, 81.6%;
      specificity, 81.8%), which was confirmed by additional regression analysis (P =
      0.007). CONCLUSIONS: Three-dimensional transesophageal echocardiography enables
      assessment of acute changes of MV geometry in patients undergoing the MitraClip
      procedure. Only patients with functional mitral regurgitation experienced
      significant reduction of MV annular dimensions, which was associated with
      clinical response to TMVR.

PMID- 24895449
TI  - Relationship between care gaps and projected life expectancy after acute
      myocardial infarction.
AB  - BACKGROUND: Higher-risk patients may not receive evidence-based therapy because
      of limited life expectancy, which is a composite measure that encompasses many
      patient factors, including age, frailty, and comorbidities. In this study, we
      evaluated the extent to which treatment care gaps can be explained by a
      difference in projected life expectancy. METHODS AND RESULTS: An observational
      cohort study was conducted on acute myocardial infarction patients hospitalized
      in Ontario, Canada. Projected life expectancy was estimated using actual survival
      data with extrapolation using proportional hazard models adjusting for important
      covariates. The relationship between projected life expectancy with statins and
      reperfusion therapy was examined using generalized linear models. Among the 7001
      acute myocardial infarction patients, 84.3% were prescribed statins and 72.9%
      were treated with reperfusion therapy. When projected life expectancy was <10
      years, the likelihood of receiving either treatment declined progressively with
      reduction in life expectancy (P<0.001). At the 25th percentile of projected life
      expectancies, the likelihood of receiving a statin decreased by 1.4% (95%
      confidence interval, 1.0-1.8%), and acute reperfusion therapy decreased by 2.6%
      (95% confidence interval, 1.8-3.3%) for each year decline in projected life
      expectancy. CONCLUSIONS: Life expectancy of a patient strongly influences
      evidence-based treatment in acute myocardial infarction. It was seen not only
      among patients with limited life expectancies but also among those with many
      years to live. Treatment care gaps may reflect clinicians' synthesis about
      frailty and life-expectancy gains.

PMID- 24895450
TI  - Sex, socioeconomic status, access to cardiac catheterization, and outcomes for
      acute coronary syndromes in the context of universal healthcare coverage.
AB  - BACKGROUND: Sex and neighborhood socioeconomic status (nSES) may independently
      affect the care and outcomes of acute coronary syndrome, partly through barriers
      in timely access to cardiac catheterization. We sought to determine whether sex
      modifies the association between nSES and the receipt of cardiac catheterization
      and mortality after an acute coronary syndrome in a universal healthcare system.
      METHODS AND RESULTS: We studied 14 012 patients with acute coronary syndrome
      admitted to cardiology services between April 18, 2004, and December 31, 2011, in
      Southern Alberta, Canada. We used multivariable logistic regression to compare
      the odds of cardiac catheterization within 2 and 30 days of admission and the
      odds of 30-day and 1-year mortality for men and women by quintile of neighborhood
      median household income. Significant relationships between nSES and the receipt
      of cardiac catheterization and mortality after acute coronary syndrome were
      detected for women but not men. When examined by nSES, each incremental decrease
      in neighborhood income quintile for women was associated with a 6% lower odds of
      receiving cardiac catheterization within 30 days (P=0.01) and a 14% higher odds
      of 30-day mortality (P=0.03). For men, each decrease in neighborhood income
      quintile was associated with a 2% lower odds of receiving catheterization within
      30 days (P=0.10) and a 5% higher odds of 30-day mortality (P=0.36). CONCLUSIONS:
      Associations between nSES and receipt of cardiac catheterization and 30-day
      mortality were noted for women but not men in a universal healthcare system. Care
      protocols designed to improve equity of access to care and outcomes are required,
      especially for low-income women.

PMID- 24895451
TI  - Impact of drug policy on regional trends in ezetimibe use.
AB  - BACKGROUND: Ezetimibe use has steadily increased in Canada during the past decade
      even in the absence of evidence demonstrating a beneficial effect on clinical
      outcomes. Among the 4 most populated provinces in Canada, there is a gradient in
      the restrictiveness of ezetimibe in public-funded formularies (most to least
      strict: British Columbia, Alberta, Quebec, and Ontario). The effect of formulary
      policy on the use of ezetimibe over time is unknown. METHODS AND RESULTS: We
      conducted a population-level cohort study using Intercontinental Marketing
      Services Health Canada's data from June 2003 to December 2012 to examine
      ezetimibe use in these 4 provinces to better understand the association between
      use and formulary restrictiveness. We found regional variations in the patterns
      of ezetimibe use. From June 2003 to December 2012, British Columbia (most
      restrictive) had the lowest monthly increasing rate from $261 to $21 926
      ($190/100 000 population/mo), whereas Ontario (least restrictive) had the most
      rapid monthly increase from $223 to $74 030 ($ 647/100 000 population/mo), and
      Quebec from $130 to $59 690 ($522/100 000 population/mo) and Alberta from $356 to
      $ 37 604 ($327/100 000 population/mo) were intermediate (P<0.001). CONCLUSIONS:
      Ezetimibe use remains common, increasing during the past decade. Use steadily
      increased in provinces with the most lenient formularies. In contrast, use was
      lower, plateauing since 2008 in British Columbia and Alberta, which have more
      restrictive formularies. The gradient in ezetimibe use was related to variability
      in restrictiveness of the provincial formularies, illustrating the potential of a
      policy response gradient that may be used to more effectively manage medication
      use.

PMID- 24895452
TI  - A comparison of clinical outcomes from carotid artery stenting among US
      hospitals.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services require hospitals
      performing carotid artery stenting (CAS) to recertify the quality of their
      programs every 2 years, but currently this involves no explicit comparisons of
      postprocedure mortality across hospitals. Hence, the current recertification
      process may fail to identify hospitals that are performing poorly in relation to
      peer institutions. Our objective was to compare risk-standardized procedural
      outcomes across US hospitals that performed CAS and to identify hospitals with
      statistically high postprocedure mortality rates. METHODS AND RESULTS: We
      conducted a retrospective cohort study of Medicare beneficiaries who underwent
      CAS from July 2009 to June 2011 at 927 US hospitals. Thirty-day risk-standardized
      mortality rates were calculated using the Hospital Compare statistical method, a
      well-validated hierarchical generalized linear model that included both patient
      level and hospital-level predictors. Claims were examined from 22 708 patients
      undergoing CAS, with a crude 30-day mortality rate of 2.0%. Risk-standardized 30
      day mortality rates after CAS varied from 1.1% to 5.1% (P<0.001 for the
      difference). Thirteen hospitals had risk-standardized mortality rates that were
      statistically (P<0.05) higher than the national mean. Conversely, 5 hospitals had
      risk-standardized mortality rates that were statistically (P<0.05) lower than the
      national mean. CONCLUSIONS: We used administrative claims to identify several CAS
      hospitals with excessively high 30-day mortality after carotid stenting. When
      combined with information currently used by Medicare for CAS recertification,
      such as clinical registry data and program reports, clinical outcomes comparisons
      could enhance Medicare's ability to identify hospitals that are questionable
      candidates for recertification.

PMID- 24895453
TI  - Atrial fibrillation and stroke prevention in aging patients: what's good can be
      even better.

PMID- 24895455
TI  - PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5
      channel expression and function.
AB  - BACKGROUND: Sodium channel NaV1.5 underlies cardiac excitability and conduction.
      The last 3 residues of NaV1.5 (Ser-Ile-Val) constitute a PDZ domain-binding motif
      that interacts with PDZ proteins such as syntrophins and SAP97 at different
      locations within the cardiomyocyte, thus defining distinct pools of NaV1.5
      multiprotein complexes. Here, we explored the in vivo and clinical impact of this
      motif through characterization of mutant mice and genetic screening of patients.
      METHODS AND RESULTS: To investigate in vivo the regulatory role of this motif, we
      generated knock-in mice lacking the SIV domain (DeltaSIV). DeltaSIV mice
      displayed reduced NaV1.5 expression and sodium current (INa), specifically at the
      lateral myocyte membrane, whereas NaV1.5 expression and INa at the intercalated
      disks were unaffected. Optical mapping of DeltaSIV hearts revealed that
      ventricular conduction velocity was preferentially decreased in the transversal
      direction to myocardial fiber orientation, leading to increased anisotropy of
      ventricular conduction. Internalization of wild-type and DeltaSIV channels was
      unchanged in HEK293 cells. However, the proteasome inhibitor MG132 rescued
      DeltaSIV INa, suggesting that the SIV motif is important for regulation of NaV1.5
      degradation. A missense mutation within the SIV motif (p.V2016M) was identified
      in a patient with Brugada syndrome. The mutation decreased NaV1.5 cell surface
      expression and INa when expressed in HEK293 cells. CONCLUSIONS: Our results
      demonstrate the in vivo significance of the PDZ domain-binding motif in the
      correct expression of NaV1.5 at the lateral cardiomyocyte membrane and underline
      the functional role of lateral NaV1.5 in ventricular conduction. Furthermore, we
      reveal a clinical relevance of the SIV motif in cardiac disease.

PMID- 24895456
TI  - Nav channel complex heterogeneity: new targets for the treatment of arrhythmia?

PMID- 24895458
TI  - Is there a need to add another dimension (time) to the evaluation of the
      arrhythmogenic potential of new drug candidates in vitro?

PMID- 24895457
TI  - Screening for acute IKr block is insufficient to detect torsades de pointes
      liability: role of late sodium current.
AB  - BACKGROUND: New drugs are routinely screened for IKr blocking properties thought
      to predict QT prolonging and arrhythmogenic liability. However, recent data
      suggest that chronic (hours) drug exposure to phosphoinositide 3-kinase
      inhibitors used in cancer can prolong QT by inhibiting potassium currents and
      increasing late sodium current (INa-L) in cardiomyocytes. We tested the extent to
      which IKr blockers with known QT liability generate arrhythmias through this
      pathway. METHODS AND RESULTS: Acute exposure to dofetilide, an IKr blocker
      without other recognized electropharmacologic actions, produced no change in ion
      currents or action potentials in adult mouse cardiomyocytes, which lack IKr. By
      contrast, 2 to 48 hours of exposure to the drug generated arrhythmogenic
      afterdepolarizations and >=15-fold increases in INa-L. Including
      phosphatidylinositol 3,4,5-trisphosphate, a downstream effector for the
      phosphoinositide 3-kinase pathway, in the pipette inhibited these effects. INa-L
      was also increased, and inhibitable by phosphatidylinositol 3,4,5-trisphosphate,
      with hours of dofetilide exposure in human-induced pluripotent stem cell-derived
      cardiomyocytes and in Chinese hamster ovary cells transfected with SCN5A,
      encoding sodium current. Cardiomyocytes from dofetilide-treated mice similarly
      demonstrated increased INa-L and afterdepolarizations. Other agents with variable
      IKr-blocking potencies and arrhythmia liability produced a range of effects on
      INa-L, from marked increases (E-4031, d-sotalol, thioridazine, and erythromycin)
      to little or no effect (haloperidol, moxifloxacin, and verapamil). CONCLUSIONS:
      Some but not all drugs designated as arrhythmogenic IKr blockers can generate
      arrhythmias by augmenting INa-L through the phosphoinositide 3-kinase pathway.
      These data identify a potential mechanism for individual susceptibility to
      proarrhythmia and highlight the need for a new paradigm to screen drugs for QT
      prolonging and arrhythmogenic liability.

PMID- 24895459
TI  - Cotargeting of epidermal growth factor receptor and PI3K overcomes PI3K-Akt
      oncogenic dependence in pancreatic ductal adenocarcinoma.
AB  - PURPOSE: PI3K-Akt is overexpressed in 50% to 70% of pancreatic ductal
      adenocarcinoma (PDAC). The hypothesis of this study is that PI3K and EGFR
      coinhibition may be effective in PDAC with upregulated PI3K-Akt signaling.
      EXPERIMENTAL DESIGN: Multiple inhibitors were tested on five PDAC cell lines.
      EGFR inhibitor (EGFRi)-resistant cell lines were found to have significantly
      overexpressed AKT2 gene, total Akt, and pAkt. In vitro erlotinib-resistant (ER)
      cell models (BxPC-ER and PANC-ER) with highly constitutively active PI3K-Akt were
      developed. These and their respective parent cell lines were tested for
      sensitivity to erlotinib, IGFIR inhibitor NVP-AEW541 (AEW), and PI3K-alpha
      inhibitor NVP-BYL719 (BYL), alone or in combination, by RTK-phosphoarray, Western
      blotting, immunofluorescence, qRT-PCR, cell proliferation, cell cycle,
      clonogenic, apoptosis, and migration assays. Erlotinib plus BYL was tested in
      vivo. RESULTS: Erlotinib acted synergistically with BYL in BxPC-ER (synergy
      index, SI = 1.71) and PANC-ER (SI = 1.44). Treatment of ER cell lines showing
      upregulated PI3K-Akt with erlotinib plus BYL caused significant G1 cell-cycle
      arrest (71%, P < 0.001; 58%, P = 0.003), inhibition of colony formation (69% and
      72%, both P < 0.001), and necrosis and apoptosis (75% and 53%, both P < 0.001),
      more so compared with parent cell lines. In primary patient-derived tumor
      subrenal capsule (n = 90) and subcutaneous (n = 22) xenografts, erlotinib plus
      BYL significantly reduced tumor volume (P = 0.005). Strong pEGFR and pAkt
      immunostaining (2+/3+) was correlated with high and low responses, respectively,
      to both erlotinib and erlotinib plus BYL. CONCLUSION: PDAC with increased
      expression of the PI3K-Akt pathway was susceptible to PI3K-EGFR coinhibition,
      suggesting oncogenic dependence. Erlotinib plus BYL should be considered for a
      clinical study in PDAC; further evaluation of pEGFR and pAkt expression as
      potential positive and negative predictive biomarkers is warranted.

PMID- 24895460
TI  - Molecular pathways: targeting NRAS in melanoma and acute myelogenous leukemia.
AB  - Successful targeting of specific oncogenic "driver" mutations with small-molecule
      inhibitors has represented a major advance in cancer therapeutics over the past
      10 to 15 years. The most common activating oncogene in human malignancy, RAS (rat
      sarcoma), has proved to be an elusive target. Activating mutations in RAS induce
      mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-AKT pathway
      signaling and drive malignant progression in up to 30% of cancers. Oncogenic NRAS
      mutations occur in several cancer types, notably melanoma, acute myelogenous
      leukemia (AML), and less commonly, colon adenocarcinoma, thyroid carcinoma, and
      other hematologic malignancies. Although NRAS-mutant tumors have been
      recalcitrant to targeted therapeutic strategies historically, newer agents
      targeting MAP/ERK kinase 1 (MEK1)/2 have recently shown signs of clinical
      efficacy as monotherapy. Combination strategies of MEK inhibitors with other
      targeted agents have strong preclinical support and are being evaluated in
      clinical trials. This review discusses the recent preclinical and clinical
      studies about the role of NRAS in cancer, with a focus on melanoma and AML.

PMID- 24895461
TI  - Influence of biospecimen variables on proteomic biomarkers in breast cancer.
AB  - BACKGROUND: PI3K/Akt/mTOR signaling is being actively pursued as a therapeutic
      target for breast cancer. We sought to determine if tumor heterogeneity and
      biospecimen variables affect the evaluation of PI3K/Akt/mTOR pathway markers.
      METHODS: Intraoperative image-guided core-needle biopsies (CNB), and central and
      peripheral surgical tumor specimens were prospectively collected in 53 patients
      with invasive breast cancer. Specimens were assessed with reverse-phase protein
      arrays (RPPA) and immunohistochemistry (IHC). RESULTS: There was a moderate or
      strong correlation between the expression of 149 (97%) of the 154 different RPPA
      markers in the center and periphery. Correlation was higher for smaller tumors,
      in patients who did not undergo neoadjuvant therapy, and with shorter cold
      ischemia time. Of 154 markers, 132 (86%) were not statistically different between
      the center and periphery, and 97 (63%) were not different between the CNB and the
      surgical specimen (average of the central and peripheral specimen). pAkt S473 and
      PTEN had a significant correlation between central and peripheral specimens, and
      between CNB and surgical specimen. However, pAkt S473, pS6 S235/236, and pS6
      240/244 levels were significantly higher in CNB than the central specimens both
      by RPPA and by IHC. CONCLUSIONS: Most individual proteomic biomarkers studied do
      not have significant intratumoral heterogeneity. However, protein and
      phosphoprotein levels are affected by biospecimen type and other preanalytic
      variables. PI3K pathway activation is greater in CNB compared with postexcision
      surgical samples suggesting a potential loss of phosphorylation during surgical
      manipulation, or with cold ischemia of surgical specimens.

PMID- 24895462
TI  - Coping and Emotion Regulation from Childhood to Early Adulthood: Points of
      Convergence and Divergence.
AB  - Processes of coping with stress and the regulation of emotion reflect basic
      aspects of development and play an important role in models of risk for
      psychopathology and the development of preventive interventions and psychological
      treatments. However, research on these two constructs has been represented in two
      separate and disconnected bodies of work. We examine possible points of
      convergence and divergence between these constructs with regard to definitions
      and conceptualization, research methods and measurement, and interventions to
      prevent and treat psychopathology. There is clear evidence that coping and
      emotion regulation are distinct but closely related constructs in all of these
      areas. The field will benefit from greater integration of methods and findings in
      future research.

PMID- 24895463
TI  - On the Role of Autonomous Control in Organ Development.
AB  - Developmental biology ("development" for short) deals with how the mature animal
      or plant results from a single fertilized cell. This paper is concerned with one
      aspect of development, morphogenesis-the formation of complex shapes from simpler
      ones. In particular, this paper focuses on organ development and illustrates the
      central role that mechanical feedback plays in effecting the final shape of
      various organs. The first aim of this paper is to illustrate how self-governing
      autonomous control systems can lead to the development of organs such as the
      heart. Although feedback plays a key role in these processes, the field is
      largely unexplored by controls engineers; hence, the second aim of this paper is
      to introduce mechanical feedback during development to controls engineers and
      suggest avenues for future research.

PMID- 24895464
TI  - Nonlinear Cascade Strategy for Longitudinal Control of Electric Vehicle.
AB  - The problem of controlling the longitudinal motion of front-wheels electric
      vehicle (EV) is considered making the focus on the case where a single dc motor
      is used for both front wheels. Chassis dynamics are modelled applying relevant
      fundamental laws taking into account the aerodynamic effects and the road slope
      variation. The longitudinal slip, resulting from tire deformation, is captured
      through Kiencke's model. Despite its highly nonlinear nature the complete model
      proves to be utilizable in longitudinal control design. The control objective is
      to achieve a satisfactory vehicle speed regulation in acceleration/deceleration
      stages, despite wind speed and other parameters uncertainty. An adaptive
      controller is developed using the backstepping design technique. The obtained
      adaptive controller is shown to meet its objectives in presence of the changing
      aerodynamics efforts and road slope.

PMID- 24895465
TI  - Compound Velocity Synchronizing Control Strategy for Electro-Hydraulic Load
      Simulator and Its Engineering Application.
AB  - An electro-hydraulic load simulator (EHLS) is a typical case of torque systems
      with strong external disturbances from hydraulic motion systems. A new velocity
      synchronizing compensation strategy is proposed in this paper to eliminate motion
      disturbances, based on theoretical and experimental analysis of a structure
      invariance method and traditional velocity synchronizing compensation controller
      (TVSM). This strategy only uses the servo-valve's control signal of motion system
      and torque feedback of torque system, which could avoid the requirement on the
      velocity and acceleration signal in the structure invariance method, and
      effectively achieve a more accurate velocity synchronizing compensation in large
      loading conditions than a TVSM. In order to facilitate the implementation of this
      strategy in engineering cases, the selection rules for compensation parameters
      are proposed. It does not rely on any accurate information of structure
      parameters. This paper presents the comparison data of an EHLS with various
      typical operating conditions using three controllers, i.e., closed loop
      proportional integral derivative (PID) controller, TVSM, and the proposed
      improved velocity synchronizing controller. Experiments are conducted to confirm
      that the new strategy performs well against motion disturbances. It is more
      effective to improve the tracking accuracy and is a more appropriate choice for
      engineering applications.

PMID- 24895466
TI  - Turbulent Heat Transfer From a Slot Jet Impinging on a Flat Plate.
AB  - The flow field and heat transfer of a plane impinging jet on a hot moving wall
      were investigated using one point closure turbulence model. Computations were
      carried out by means of a finite volume method. The evolutions of mean velocity
      components, vorticity, skin friction coefficient, Nusselt number and pressure
      coefficient are examined in this paper. Two parameters of this type of
      interaction are considered for a given impinging distance of 8 times the nozzle
      thickness (H/e = 8): the jet-surface velocity ratio and the jet exit Reynolds
      number. The flow field structure at a given surface-to-jet velocity ratio is
      practically independent to the jet exit Reynolds number. A slight modification of
      the flow field is observed for weak surface-to-jet velocity ratios while the jet
      is strongly driven for higher velocity ratio. The present results satisfactorily
      compare to the experimental data available in the literature for Rsj <= 1.The
      purpose of this paper is to investigate this phenomenon for higher Rsj values (0
      <= Rsj <= 4). It follows that the variation of the mean skin friction and the
      Nusselt number can be correlated according to the surface-to-jet velocity ratios
      and the Reynolds numbers.

PMID- 24895467
TI  - Effect of the Heat Pipe Adiabatic Region.
AB  - The main motivation of conducting this work is to present a rigorous analysis and
      investigation of the potential effect of the heat pipe adiabatic region on the
      flow and heat transfer performance of a heat pipe under varying evaporator and
      condenser conditions. A two-dimensional steady-state model for a cylindrical heat
      pipe coupling, for both regions, is presented, where the flow of the fluid in the
      porous structure is described by Darcy-Brinkman-Forchheimer model which accounts
      for the boundary and inertial effects. The model is solved numerically by using
      the finite volumes method, and a fortran code was developed to solve the system
      of equations obtained. The results show that a phase change can occur in the
      adiabatic region due to temperature gradient created in the porous structure as
      the heat input increases and the heat pipe boundary conditions change. A
      recirculation zone may be created at the condenser end section. The effect of the
      heat transfer rate on the vapor radial velocities and the performance of the heat
      pipe are discussed.

PMID- 24895468
TI  - Numerical Simulation of Bubble Cluster Induced Flow by Three-Dimensional Vortex
      in-Cell Method.
AB  - The behavior of air bubble clusters rising in water and the induced flow field
      are numerically studied using a three-dimensional two-way coupling algorithm
      based on a vortex-in-cell (VIC) method. In this method, vortex elements are
      convected in the Lagrangian frame and the liquid velocity field is solved from
      the Poisson equation of potential on the Eulerian grid. Two-way coupling is
      implemented by introducing a vorticity source term induced by the gradient of
      void fraction. Present simulation results are favorably compared with the
      measured results of bubble plume, which verifies the validity of the proposed VIC
      method. The rising of a single bubble cluster as well as two tandem bubble
      clusters are simulated. The mechanism of the aggregation effect in the rising
      process of bubble cluster is revealed and the transient processes of the
      generation, rising, strengthening, and separation of a vortex ring structure with
      bubble clusters are illustrated and analyzed in detail. Due to the aggregation,
      the average rising velocity increases with void fraction and is larger than the
      terminal rising velocity of single bubble. For the two tandem bubble cluster
      cases, the aggregation effect is stronger for smaller initial cluster distance,
      and both the strength of the induced vortex structure and the average bubble
      rising velocity are larger. For the 20 mm cluster distance case, the peak
      velocity of the lower cluster is about 2.7 times that of the terminal velocity of
      the single bubble and the peak average velocity of two clusters is about 2 times
      larger. While for the 30 mm cluster distance case, both the peak velocity of the
      lower cluster and two clusters are about 1.7 times that of the terminal velocity
      of the single bubble.

PMID- 24895469
TI  - Further evidence that a terminal drought tolerance QTL of pearl millet is
      associated with reduced salt uptake.
AB  - Earlier, we established that a major drought tolerance QTL on linkage group 2 of
      pearl millet is also associated with reduced salt uptake and enhanced growth
      under salt stress. Present study was undertaken to re-assess the performance of
      drought tolerant (PRLT 2/89-33) and drought sensitive (H 77/833-2) parents along
      with two QTL-NILs (ICMR 01029 and ICMR 01040), under salinity stress specifically
      imposed during post-flowering growth stages when plants had developed their ion
      sinks in full. Time course changes in ionic accumulation and their
      compartmentalization in different plant parts was studied, specifically to
      monitor and capture changes conferred by the two alleles at this QTL, at small
      intervals. Amongst different plant parts, higher accumulation of toxic ion Na+
      was recorded in roots. Further, the Na+ concentration in roots of the testcross
      hybrid of the drought-sensitive parent (H 77/833-2) reached its maximum at ECiw
      15 dS m-1 within 24 h after salinity imposition, whereas it continued to increase
      with time in the testcross hybrids of the drought tolerant parent PRLT 2/89-33 as
      well as those of its QTL-NILs (ICMR 01029 and ICMR 01004) and reached at its
      maximum at 120 h stage. Comparison of differential distribution of toxic ions in
      individual leaves revealed that Na+ ions were not uniformly distributed in the
      leaves of the drought-tolerant parent and drought-tolerant QTL-NILs; but
      accumulated preferentially in the older leaves, whereas the hybrid of the drought
      sensitive parent showed significantly higher Na+ concentration in all main stem
      leaves irrespective of their age. Dynamics of chlorophyll and proline
      concentration variation studied under salt stress at late flowering stages
      revealed a greater reduction, almost twice, in both leaf chlorophyll and proline
      concentrations in younger leaves in the hybrids of the sensitive parent as
      compared to the tolerant parent and QTL NILs. Imposition of salinity stress even
      at flowering stage affected the yield performance in pearl millet, wherein higher
      yield was recorded in drought tolerant parent and the two QTL-NILs compared to
      drought sensitive parent.

PMID- 24895471
TI  - Assessment of multiresolution segmentation for delimiting drumlins in digital
      elevation models.
AB  - Mapping or "delimiting" landforms is one of geomorphology's primary tools.
      Computer-based techniques such as land-surface segmentation allow the emulation
      of the process of manual landform delineation. Land-surface segmentation
      exhaustively subdivides a digital elevation model (DEM) into morphometrically
      homogeneous irregularly-shaped regions, called terrain segments. Terrain segments
      can be created from various land-surface parameters (LSP) at multiple scales, and
      may therefore potentially correspond to the spatial extents of landforms such as
      drumlins. However, this depends on the segmentation algorithm, the
      parameterization, and the LSPs. In the present study we assess the widely used
      multiresolution segmentation (MRS) algorithm for its potential in providing
      terrain segments which delimit drumlins. Supervised testing was based on five 5-m
      DEMs that represented a set of 173 synthetic drumlins at random but
      representative positions in the same landscape. Five LSPs were tested, and four
      variants were computed for each LSP to assess the impact of median filtering of
      DEMs, and logarithmic transformation of LSPs. The testing scheme (1) employs MRS
      to partition each LSP exhaustively into 200 coarser scales of terrain segments by
      increasing the scale parameter (SP), (2) identifies the spatially best matching
      terrain segment for each reference drumlin, and (3) computes four segmentation
      accuracy metrics for quantifying the overall spatial match between drumlin
      segments and reference drumlins. Results of 100 tests showed that MRS tends to
      perform best on LSPs that are regionally derived from filtered DEMs, and then log
      transformed. MRS delineated 97% of the detected drumlins at SP values between 1
      and 50. Drumlin delimitation rates with values up to 50% are in line with the
      success of manual interpretations. Synthetic DEMs are well-suited for assessing
      landform quantification methods such as MRS, since subjectivity in the reference
      data is avoided which increases the reliability, validity and applicability of
      results.

PMID- 24895470
TI  - An objective approach to model reduction: Application to the Sirius wheat model.
AB  - An existing simulation model of wheat growth and development, Sirius, was
      evaluated through a systematic model reduction procedure. The model was
      automatically manipulated under software control to replace variables within the
      model structure with constants, individually and in combination. Predictions of
      the resultant models were compared to growth analysis observations of total
      biomass, grain yield, and canopy leaf area derived from 9 trials conducted in the
      UK and New Zealand under optimal, nitrogen limiting and drought conditions. Model
      performance in predicting these observations was compared in order to evaluate
      whether individual model variables contributed positively to the overall
      prediction. Of the 1 1 1 model variables considered 16 were identified as
      potentially redundant. Areas of the model where there was evidence of redundancy
      were: (a) translocation of biomass carbon to grain; (b) nitrogen physiology; (c)
      adjustment of air temperature for various modelled processes; (d) allowance for
      diurnal variation in temperature; (e) vernalisation (f) soil nitrogen
      mineralisation (g) soil surface evaporation. It is not suggested that these are
      not important processes in real crops, rather, that their representation in the
      model cannot be justified in the context of the analysis. The approach described
      is analogous to a detailed model inter-comparison although it would be better
      described as a model intra-comparison as it is based on the comparison of many
      simplified forms of the same model. The approach provides automation to increase
      the efficiency of the evaluation and a systematic means of increasing the rigour
      of the evaluation.

PMID- 24895472
TI  - Creativity and personality in classical, jazz and folk musicians.
AB  - The music genre of jazz is commonly associated with creativity. However, this
      association has hardly been formally tested. Therefore, this study aimed at
      examining whether jazz musicians actually differ in creativity and personality
      from musicians of other music genres. We compared students of classical music,
      jazz music, and folk music with respect to their musical activities, psychometric
      creativity and different aspects of personality. In line with expectations, jazz
      musicians are more frequently engaged in extracurricular musical activities, and
      also complete a higher number of creative musical achievements. Additionally,
      jazz musicians show higher ideational creativity as measured by divergent
      thinking tasks, and tend to be more open to new experiences than classical
      musicians. This study provides first empirical evidence that jazz musicians show
      particularly high creativity with respect to domain-specific musical
      accomplishments but also in terms of domain-general indicators of divergent
      thinking ability that may be relevant for musical improvisation. The findings are
      further discussed with respect to differences in formal and informal learning
      approaches between music genres.

PMID- 24895474
TI  - Traveling surface waves of moderate amplitude in shallow water.
AB  - We study traveling wave solutions of an equation for surface waves of moderate
      amplitude arising as a shallow water approximation of the Euler equations for
      inviscid, incompressible and homogeneous fluids. We obtain solitary waves of
      elevation and depression, including a family of solitary waves with compact
      support, where the amplitude may increase or decrease with respect to the wave
      speed. Our approach is based on techniques from dynamical systems and relies on a
      reformulation of the evolution equation as an autonomous Hamiltonian system which
      facilitates an explicit expression for bounded orbits in the phase plane to
      establish existence of the corresponding periodic and solitary traveling wave
      solutions.

PMID- 24895475
TI  - Introduction to serial reviews: Oxidative stress biomarker and its application to
      health maintenance.

PMID- 24895473
TI  - Beta2-microglobulin as a diagnostic marker in cerebrospinal fluid: a follow-up
      study.
AB  - Beta2-Microglobulin ( beta 2-m) is a low molecular weight protein occurring in
      all body fluids. Its concentration increases in various pathologies. Increased
      values in cerebrospinal fluid (CSF) are ascribed to an activation of immune
      system. Using immunoturbidimetry, we examined concentrations of beta2
      microglobulin in cerebrospinal fluid in a large group of 6274 patients with
      defined neurological diseases. Cell counts, total protein, albumin, glucose,
      lactic acid, immunoglobulins concentrations, and isofocusing (IEF) were also
      evaluated. We found substantial changes of CSF beta 2-m concentrations in
      purulent meningitis, leptomeningeal metastasis, viral meningitis/encephalitis,
      and neuroborreliosis, while in multiple sclerosis these changes were not
      significant. Intrathecal synthesis and immune activation were present in these
      clinical entities. A new normative study enables better understanding of beta2
      microglobulin behavior in CSF. 

PMID- 24895476
TI  - beta-Glucuronidase activity and mitochondrial dysfunction: the sites where
      flavonoid glucuronides act as anti-inflammatory agents.
AB  - Epidemiological and experimental studies suggest that the consumption of
      flavonoid-rich diets decreases the risk of various chronic diseases such as
      cardiovascular diseases. Although studies on the bioavailability of flavonoids
      have been well-characterized, the tissue and cellular localizations underlying
      their biological mechanisms are largely unknown. The development and application
      of novel monoclonal antibodies revealed that macrophages could be the major
      target of dietary flavonoids in vivo. Using macrophage-like cell lines in vitro,
      we examined the molecular basis of the interaction between the macrophages and
      flavonoids, especially the glucuronide metabolites. We have found that
      extracellular beta-glucuronidase secreted from macrophages is essential for the
      bioactivation of the glucuronide conjugates into the aglycone, and that the
      enzymatic activity, which requires an acidic pH, is promoted by the increased
      secretion of lactate in response to the mitochondrial dysfunction. This review
      describes our recent findings indicating the molecular mechanisms responsible for
      the anti-inflammatory activity of dietary flavonoids within the inflammation
      sites. We propose that the extracellular activity of beta-glucuronidase
      associated with the status of the mitochondrial function in the target cells
      might be important biomarkers for the specific sites where the glucuronides of
      dietary flavonoids can act as anti-atherosclerotic and anti-inflammatory agents
      in vivo. 

PMID- 24895478
TI  - Bactericidal effect of hydroxyl radicals generated from a low concentration
      hydrogen peroxide with ultrasound in endodontic treatment.
AB  - One approach to enhance the disinfection of root canals in endodontic treatment
      is ultrasonic irrigation with sodium hypochlorite. Reactive oxygen species, such
      as hydroxyl radical, are generated by biological defense systems to kill invading
      bacteria. Ultrasonic irrigation with hydrogen peroxide may be a promising option
      to increase hydroxyl radical generation. We examined the bactericidal effects of
      hydroxyl radical generated from low concentration hydrogen peroxide with
      ultrasound in vitro. An ultrasonic tip was submerged in 0.5 or 1.0 M hydrogen
      peroxide in a microfuge tube. hydrogen peroxide was irradiated with the
      ultrasound, the tip of which was maintained centered in the tube to mimic
      ultrasonic irrigation. Hydroxyl radical generation was assessed by electron spin
      resonance spectroscopy. Subsequently, Enterococcus faecalis suspension in
      hydrogen peroxide was prepared and irradiated as described above. Bactericidal
      effects were assessed by viable counting. Electron spin resonance measurements
      showed that hydroxyl radical generation increased significantly in a time- and
      dose-dependent manner (two-way analysis of variance and Tukey's test, p<0.05).
      Moreover, the bactericidal effects of hydrogen peroxide against Enterococcus
      faecalis were enhanced by ultrasonic irradiation in a time- and dose-dependent
      manner. These results suggest that ultrasonic irrigation in the presence of low
      concentration hydrogen peroxide can serve as a disinfection strategy in
      endodontic treatment. 

PMID- 24895477
TI  - The role of lipid peroxidation in neurological disorders.
AB  - There has been much evidence demonstrating the involvement of oxidative stress in
      the pathology of neurological disorders. Moreover, the vulnerability of the
      central nervous system to reactive oxygen species mediated injury is well
      established since neurons consume large amounts of oxygen, the brain has many
      areas containing high iron content, and neuronal mitochondria generate large
      amounts of hydrogen peroxide. Furthermore, neuronal membranes are rich in
      polyunsaturated fatty acids, which are particularly susceptible to oxidative
      stress. Recently, the biological roles of products produced by lipid peroxidation
      have received much attention, not only for their pathological mechanisms
      associated with neurological disorders, but also for their practical clinical
      applications as biomarkers. Here, we discuss the production mechanisms of
      reactive oxygen species in some neurological disorders, including Alzheimer's
      disease, Down syndrome, Parkinson's disease, and stroke. We also describe lipid
      peroxidation biomarkers for evaluating oxidative stress. 

PMID- 24895479
TI  - The behavior of ROS-scavenging nanoparticles in blood.
AB  - Here, we report an interaction between blood and redox nanoparticles, prepared by
      self-assembly of amphiphilic block copolymers possessing 2,2,6,6
      tetramethylpiperidine-N-oxyls as a side chain of hydrophobic segment. When 4
      hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl was added to rat whole blood, its
      electron spin resonance signal disappeared rapidly. In contrast, the signal from
      redox nanoparticles remained for a long period of time, indicating that nitroxide
      radicals were protected in the blood by their compartmentalization in the core of
      nanoparticle. Although most 2,2,6,6-tetramethylpiperidine-N-oxyls were located in
      the nanoparticle core, reactive oxygen species-scavenging activity was found
      outside of blood cells. For example, redox nanoparticles suppressed superoxide
      anion-induced hemolysis effectively, while 4-hydroxy-2,2,6,6
      tetramethylpiperidine-N-oxyl did not. It was revealed that redox nanoparticles
      were not internalized into the healthy blood cells, which was in sharp contrast
      to 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. Due to its internalization
      into healthy platelets, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl induced
      mitochondrial dysfunction, while redox nanoparticles did not. Redox nanoparticles
      suppressed platelet adhesion and extended blood coagulation time, in contrast to
      4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. These results indicate that redox
      nanoparticles scavenge reactive oxygen species outside of cells, but do not
      interfere with normal redox reactions inside of the cell. Based on these results,
      we determine that an anti-oxidative strategy based on nanotechnology is a
      rational and safe therapeutic approach. 

PMID- 24895480
TI  - Intercorrelations of lipoprotein subfractions and their covariation with
      lifestyle factors in healthy men.
AB  - So far, little is known about the effect of nutrition and lifestyle on the
      composition of circulating lipoprotein subfractions. In the current study, we
      measured the correlations among physical activity, nutrient intake, smoking, body
      mass index (BMI), and age with the concentration of triglycerides, cholesterol,
      phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL
      and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids,
      and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively
      (p<0.001) with those of cholesterol, phospholipids, and ApoA1 in HDL2,
      respectively. Age correlated positively with sdLDL while increasing BMI
      correlated with an atherogenic shift of cholesterol, phospholipids, and ApoB from
      large, buoyant LDL (lbLDL) to sdLDL and decreasing concentrations of HDL2
      constituents. Physical activity and alcohol intake correlated negatively with
      sdLDL constituents and positively with HDL2 components. Consumption of
      monounsaturated fatty acids (MUFA) correlated with a lower ratio of sdLDL to HDL2
      cholesterol. A favorable lipoprotein subfraction profile linked to a reduced risk
      of cardiovascular disease in men was associated with physical activity, moderate
      alcohol consumption, and dietary intake of MUFA, which might be exploited in
      future interventions for prevention of age- and BMI-associated atherogenic shifts
      of lipoprotein subfractions. 

PMID- 24895481
TI  - BRP, a polysaccharide fraction isolated from Boschniakia rossica, protects
      against galactosamine and lipopolysaccharide induced hepatic failure in mice.
AB  - The aim of this study was to investigate the hepatoprotective effect of BRP, a
      polysaccharide fraction isolated from Boschniakia rossica, against galactosamine
      and lipopolysaccharide induced fulminant hepatic failure. Mice were injected with
      a single dose of galactosamine/lipopolysaccharide with or without pretreatment of
      BRP. Results showed marked reduction of hepatic necrosis, serum marker enzymes
      and levels of tumor necrosis factor-alpha and interleukin-6 in BRP pretreated
      mice when compared with galactosamine/lipopolysaccharide-challenged mice. Mice
      pretreated with BRP decreased the activation of caspases-3 and caspase-8, and
      showed a reduced level of DNA fragmentation of liver cells. BRP also reduced
      hepatic lipid peroxidation, increased potential of hepatic antioxidative defense
      system, and reduced hepatic nitric oxide level which was elevated by
      galactosamine/lipopolysaccharide injection. Immunoblot analysis showed down
      regulation of inducible nitric oxide synthase and cyclooxygenase-2 proteins of
      liver tissues in BRP pretreated group when compared with
      galactosamine/lipopolysaccharide-challenged group. Furthermore, treatment with
      galactosamine/lipopolysaccharide markedly increased toll-like receptor 4, nuclear
      level of nuclear factor-kappaB, and phosphorylation of both extracellular signal
      regulated kinase and c-Jun N-terminal kinase in liver tissues. However, these
      increases were attenuated by pretreatment with BRP. The results suggest that BRP
      alleviates galactosamine/lipopolysaccharide-induced liver injury by enhancing
      antioxidative defense system, suppressing inflammatory responses and reducing
      apoptotic signaling. 

PMID- 24895482
TI  - The alpha-tocopherol status and expression of alpha-tocopherol-related proteins
      in methionine-choline deficient rats treated with vitamin E.
AB  - Non-alcoholic fatty liver disease is the most common liver disorder in developed
      countries, and its incidence is increasing in all population groups. As an
      antioxidant, vitamin E is effective in the treatment of non-alcoholic fatty liver
      disease, although the mechanism is still unclear. Methionine-choline deficient
      Wistar rats (n = 5) used as an experimental model of non-alcoholic fatty liver
      disease were fed a vitamin E-enriched diet (500 mg/kg) for 4 weeks. The effects
      were assessed by measuring lipid peroxidation, alpha-tocopherol levels, and the
      expression of alpha-tocopherol-related proteins in the liver. In vitamin E
      treated methionine-choline deficient rats, lipid peroxidation was reduced, but
      liver histopathological changes were not improved. Hepatic alpha-tocopherol
      levels in these rats were significantly elevated compared to normal rats treated
      with vitamin E. Expression of liver alpha-tocopherol transfer protein in vitamin
      E-treated methionine-choline deficient rats was significantly repressed compared
      to methionine-choline deficient rats. The expression of liver cytochrome P450 4F2
      and ATP-binding cassette transporter protein 1, involved in metabolism and
      transport of alpha-tocopherol, respectively, was significantly repressed in
      vitamin E-treated methionine-choline deficient rats. In methionine-choline
      deficient rats, vitamin E treatment altered the hepatic alpha-tocopherol-related
      protein expression, which may affect alpha-tocopherol status in the liver,
      leading to reduced lipid peroxidation. 

PMID- 24895483
TI  - No correlation is found for vegetables between antioxidant capacity and potential
      benefits in improving antioxidant function in aged rats.
AB  - Vegetables vary greatly in antioxidant capacity in vitro. This study was to
      investigate the actions of three vegetables different remarkably in antioxidant
      capacity in vitro on antioxidant function in aged rats. Sixty female aged Wistar
      rats were randomly assigned to the control, lotus root, rape and cucumber (high,
      moderate and low in antioxidant capacity, respectively) treated groups. After 6
      weeks of feeding, there were no significant differences in plasma FRAP value and
      contents of vitamin C, vitamin E, uric acid and total phenolics among different
      groups, whereas the content of reduced glutathione was significantly higher in
      the rape and cucumber groups. Plasma superoxide dismutase activity also was
      significantly increased in the rape and cucumber groups. Plasma contents of
      malondialdehyde, carbonyls and hemolysis were decreased significantly in 3
      vegetable-treated groups. Meanwhile, urinary 8-hydroxy-2'-deoxyguanosine
      excretion was lower significantly in the rape group and the ratio of comet tail
      length to total length of blood mononuclear cells was decreased significantly in
      3 vegetables treated groups. These results suggest that 3 vegetables tested are
      effective in improving antioxidant function to some extent in aged rats and no
      correlation is found between antioxidant capacity in vitro and improvements of
      antioxidant function. The benefits observed in this study may come from additive
      or synergistic combinations of antioxidants contained in vegetables. 

PMID- 24895485
TI  - Retraction: d-Psicose inhibits intestinal alpha-glucosidase and suppresses the
      glycemic response after ingestion of carbohydrate in rats.

PMID- 24895484
TI  - Assessment of metabolic status in young Japanese females using postprandial
      glucose and insulin levels.
AB  - Lifestyle-related diseases develop through the accumulation of undesirable
      lifestyle habits both prior to the onset of disease as well as during normal
      healthy life. Accordingly, early detection of, and intervention in, metabolic
      disorders is desirable, but is hampered by the lack of an established evaluation
      index for young individuals. The purpose of this study was to investigate the
      utility of a biomarker of health in young female subjects. The subjects were
      young healthy Japanese females in whom energy expenditure was measured for a
      period of 210 min after a test meal. In addition, Deltaplasma glucose and
      Deltaserum insulin were calculated from the fasting and 30 min values.
      DeltaPlasma glucose and Deltaserum insulin levels varied widely compared to
      fasting levels. Both the area under the curve of carbohydrate oxidation rate and
      serum free fatty acid levels were higher in individuals in the high Deltaplasma
      glucose group. Moreover, Deltaplasma glucose was higher in individuals in the
      high Deltaserum insulin group than in the low Deltaserum insulin group. We
      conclude that nutritional balanced liquid loading test using Deltaplasma glucose
      and Deltaserum insulin as the evaluation index is useful for the detection of
      primary metabolic disorders in young females. 

PMID- 24895486
TI  - The cognitive neurology of bilingualism in the age of globalization.

PMID- 24895487
TI  - Can tics be performed convincingly by an actor?
AB  - BACKGROUND: In the German movie "Vincent will Meer" a healthy actor portrays a
      man with Tourette's syndrome. Objective. The aim of this study was to investigate
      whether the performance of tics is convincing and whether this judgment depends
      on whether he/she suffers from tics or not. METHODS: While the movie was
      broadcasted in German cinemas, we put an online survey (including 28 questions on
      different aspects related to the observation, performance, and authenticity of
      tics) on the web pages of the German self-help group. 276/296 surveys submitted
      could be used for further analyses. RESULT: 95.7% of all participants felt that
      the performance of tics was convincing. However, people with tics (n = 26) were
      less convinced compared to those who had never met a person with tics (n = 110)
      (P = 0.020). CONCLUSIONS: Our results further support the hypothesis that tics
      are not "abnormal" but "physiological" movements that are only misplaced both in
      time and context.

PMID- 24895489
TI  - Th22 cell is a gradually proved potential biomarker for acute coronary syndrome.

PMID- 24895490
TI  - An Analytical Approach for Synthesizing Line Actuation Spaces of Parallel Flexure
      Mechanisms.
AB  - In this study, we present an analytical approach for synthesizing line actuation
      spaces of a parallel flexure mechanism (PFM) that can help designers to arrange
      linear actuators within the PFM in a correct and optimal way. On the basis of
      screw theory and upon an assumption of small deformations, an important synthesis
      criterion stated as "any actuation space of a flexure mechanism is always
      linearly independent of its constraint space" has been derived and disclosed for
      the first time. Guided by this criterion, a general synthesis process for the
      line actuation spaces of PFMs is introduced and demonstrated with several
      selective examples. The proposed synthesis criterion and process will enable
      designers to (i) systematically formulate line actuation spaces in the format of
      screw systems; (ii) likely yield a multiple solution to actuation spaces; and
      (iii) potentially determine an optimal result from those alternatives for
      actuator placement.

PMID- 24895491
TI  - Spectral Characterization of Hierarchical Modularity in Product Architectures.
AB  - Despite the importance of the architectural modularity of products and systems,
      existing modularity metrics or algorithms do not account for overlapping and
      hierarchically embedded modules. This paper presents a graph theoretic spectral
      approach to characterize the degree of modular hierarchical-overlapping
      organization in the architecture of products and complex engineered systems. It
      is shown that the eigenvalues of the adjacency matrix of a product architecture
      graph can reveal layers of hidden modular or hierarchical modular organization
      that are not immediately visible in the predefined architectural description. We
      use the approach to analyze and discuss several design, management, and system
      resilience implications for complex engineered systems.

PMID- 24895488
TI  - Physical exercise reduces the expression of RANTES and its CCR5 receptor in the
      adipose tissue of obese humans.
AB  - RANTES and its CCR5 receptor trigger inflammation and its progression to insulin
      resistance in obese. In the present study, we investigated for the first time the
      effect of physical exercise on the expression of RANTES and CCR5 in obese humans.
      Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a
      3-month supervised physical exercise. RANTES and CCR5 expressions were measured
      in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating
      plasma levels of RANTES were also investigated. There was a significant increase
      in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese
      compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein
      were comparable between both groups, CCR5 mRNA was downregulated in obese
      subjects (P < 0.05). Physical exercise significantly reduced the expression of
      both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a
      concomitant decrease in the levels of the inflammatory markers TNF- alpha , IL-6,
      and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1
      ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P <
      0.05). Therefore, physical exercise may provide an effective approach for
      combating the deleterious effects associated with obesity through RANTES
      signaling in the adipose tissue.

PMID- 24895492
TI  - Nonlinear Strain Energy Formulation of a Generalized Bisymmetric Spatial Beam for
      Flexure Mechanism Analysis.
AB  - Analytical load-displacement relations for flexure mechanisms, formulated by
      integrating the individual analytical models of their building-blocks (i.e.,
      flexure elements), help in understanding the constraint characteristics of the
      whole mechanism. In deriving such analytical relations for flexure mechanisms,
      energy based approaches generally offer lower mathematical complexity, compared
      to Newtonian methods, by reducing the number of unknowns-specifically, the
      internal loads. To facilitate such energy based approaches, a closed-form
      nonlinear strain energy expression for a generalized bisymmetric spatial beam
      flexure is presented in this paper. The strain energy, expressed in terms of the
      end-displacement of the beam, considers geometric nonlinearities for intermediate
      deformations, enabling the analysis of flexure mechanisms over a finite range of
      motion. The generalizations include changes in the initial orientation and shape
      of the beam flexure due to potential misalignment or manufacturing. The
      effectiveness of this approach is illustrated via the analysis of a multilegged
      table flexure mechanism. The resulting analytical model is shown to be accurate
      using nonlinear finite elements analysis, within a load and displacement range of
      interest.

PMID- 24895493
TI  - DNA Cleavage, Cytotoxic Activities, and Antimicrobial Studies of Ternary
      Copper(II) Complexes of Isoxazole Schiff Base and Heterocyclic Compounds.
AB  - Novel mixed ligand bivalent copper complexes [Cu. L. A. ClO 4 ] and [Cu. L. A]
      where "L" is Schiff bases, namely 2-((3,4-dimethylisoxazol-5-ylimino)methyl)-4
      bromophenol (DMIIMBP)/2-((3,4-dimethylisoxazol-5-ylimino)methyl)-4-chlorophenol
      (DMIIMCP), and "A" is heterocyclic compound, such as 1,10-phenanthroline
      (phen)/2,2(1)-bipyridyl (bipy)/8-hydroxyquinoline (oxine)/5-chloro-8
      hydroxyquinoline (5-Cl-oxine), have been synthesized. These complexes have been
      characterized by IR, UV-Vis, ESR, elemental analysis, magnetic moments, TG, and
      DTA. On the basis of spectral studies and analytical data, five-coordinated
      square pyramidal/four-coordinated square planar geometry is assigned to all
      complexes. The ligands and their ternary complexes with Cu(II) have been screened
      for antimicrobial activity against bacteria and fungi by paper disc method. The
      antimicrobial studies of Schiff bases and their metal complexes showed
      significant activity and further it is observed that the metal complexes showed
      more activity than corresponding Schiff bases. In vitro antitumor activity of
      Cu(II) complexes was assayed against human cervical carcinoma (HeLa) cancer cells
      and it was observed that few complexes exhibit good antitumor activity on HeLa
      cell lines. The DNA cleavage studies have also been carried out on pBR 322 and it
      is observed that these Cu(II) complexes are capable of cleaving supercoiled
      plasmid DNA in the presence of H2O2 and UV light. 

PMID- 24895494
TI  - Identification and Validation of Expressed Sequence Tags from Pigeonpea (Cajanus
      cajan L.) Root.
AB  - Pigeonpea (Cajanus cajan (L) Millsp.) is an important food legume crop of rain
      fed agriculture in the arid and semiarid tropics of the world. It has deep and
      extensive root system which serves a number of important physiological and
      metabolic functions in plant development and growth. In order to identify genes
      associated with pigeonpea root, ESTs were generated from the root tissues of
      pigeonpea (GRG-295 genotype) by normalized cDNA library. A total of 105 high
      quality ESTs were generated by sequencing of 250 random clones which resulted in
      72 unigenes comprising 25 contigs and 47 singlets. The ESTs were assigned to 9
      functional categories on the basis of their putative function. In order to
      validate the possible expression of transcripts, four genes, namely, S
      adenosylmethionine synthetase, phosphoglycerate kinase, serine carboxypeptidase,
      and methionine aminopeptidase, were further analyzed by reverse transcriptase
      PCR. The possible role of the identified transcripts and their functions
      associated with root will also be a valuable resource for the functional genomics
      study in legume crop. 

PMID- 24895495
TI  - Iatrogenic cushing syndrome secondary to ritonavir-epidural triamcinolone
      interaction: an illustrative case and review.
AB  - HIV positive patients on ritonavir-containing antiretroviral therapy (ART) can
      develop iatrogenic Cushing syndrome (IACS) and adrenal insufficiency as a result
      of drug-drug interactions with inhaled or intranasal glucocorticoid therapy.
      Reports related to epidural triamcinolone injections are relatively uncommon but
      increasingly reported. We describe a 48-year-old woman with immunologically and
      virologically well-controlled HIV on ritonavir-based ART, who developed headache,
      dizziness, and candida and herpes simplex virus (HSV) ulcerative esophagitis 7
      days after receiving an epidural triamcinolone injection for cervical radicular
      pain. Iatrogenic Cushing syndrome and relative adrenal insufficiency were
      suspected and proven. The patient's ART was changed to a non-HIV protease
      inhibitor- (PI-) containing program, her symptoms improved, and she did not
      require hydrocortisone replacement. In this paper, we review the literature on
      IACS and relative secondary adrenal insufficiency from epidural triamcinolone
      injections in HIV patients on ritonavir-containing ART regimens. A high index of
      clinical suspicion is needed for diagnosis. Prevention of drug-drug interactions
      by taking a thorough medication history for patients on ritonavir-containing ART
      regimens before prescribing any form of corticosteroid is crucial and effective
      and sustained interdisciplinary communication in the care of such patients. 

PMID- 24895496
TI  - Adrenocortical production is associated with higher levels of luteinizing hormone
      in nonobese women with polycystic ovary syndrome.
AB  - Objective. Insulin resistance (IR) and ovarian and adrenal hyperandrogenism are a
      common finding in women with polycystic ovary syndrome (PCOS). The aim of the
      present study was to access possible differences in insulin resistance,
      gonadotropins, and androgens production in obese and nonobese PCOS women. Study
      Design. We studied 37 PCOS women (16 nonobese and 21 obese) and 18 nonobese
      controls. Fasting glucose, insulin, androgens, and gonadotropins levels were
      determined. Salivary cortisol was measured basal and in the morning after
      dexamethasone (DEX) 0.25 mg. Results. Nonobese PCOS women showed higher basal
      salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing
      hormone (LH) levels than controls and obese PCOS. These hormones levels did not
      differ between the obese and control groups. After DEX administration no
      differences were found between the three groups. In PCOS women, salivary cortisol
      levels showed negative correlation with BMI (r = -0.52; P = 0.001) and insulin (r
      = -0.47; P = 0.003) and positive correlation with LH (r = 0.40; P = 0.016).
      Conclusion. Our results show an increased adrenocortical production in nonobese
      PCOS women, not related to IR and associated with a normal hypothalamic-pituitary
      adrenal suppression. Higher LH levels might be involved in this event. 

PMID- 24895498
TI  - Peristeen (c) transanal irrigation system for paediatric faecal incontinence: a
      single centre experience.
AB  - Aim. To evaluate the efficacy of the Peristeen (C) transanal irrigation system
      when treating faecal incontinence in children due to chronic idiopathic
      constipation. Methods. A retrospective study was conducted of the first cohort of
      patients affected with faecal incontinence and referred to our centre for
      Peristeen (C) transanal irrigation treatment between January 2010 and December
      2012. Patients with neurogenic bowel disturbance were excluded. A previously
      described and validated faecal continence scoring system was used to assess bowel
      function and social problems before and after treatment with Peristeen (C) .
      Results. 13 patients were referred for Peristeen (C) transanal irrigation during
      the study period. Mean time of using Peristeen (C)   was 12.6 months (+/-0.6
      months) and mean length of follow-up was 21.2 months (+/-0.9 months). All
      patients were noted to have an improvement in their faecal continence score, with
      a mean improvement from 9.7 +/- 1.4 to 14.8 +/- 2.7 (P = 0.0008) and a reduction
      in episodes of soiling and increasing in quality of life scores. Conclusion. In
      this initial study, Peristeen (C) appears to be a safe and effective bowel
      management system, which improves bowel function and quality of life in children
      affected with faecal incontinence as a result of chronic idiopathic constipation,
      Hirschsprung's disease, and anorectal malformations. 

PMID- 24895497
TI  - Population-based placental weight ratio distributions.
AB  - The placental weight ratio (PWR) is a health indicator that reflects the balance
      between fetal and placental growth. The PWR is defined as the placental weight
      divided by the birth weight, and it changes across gestation. Its ranges are not
      well established. We aimed to establish PWR distributions by gestational age and
      to investigate whether the PWR distributions vary by fetal growth adequacy,
      small, average, and large for gestational age (SGA, AGA, and LGA). The data came
      from a hospital based retrospective cohort, using all births at two London,
      Ontario hospitals in the past 10 years. All women who delivered a live singleton
      infant between 22 and 42 weeks of gestation were included (n = 41441).
      Nonparametric quantile regression was used to fit the curves. The results
      demonstrate decreasing PWR and dispersion, with increasing gestational age. A
      higher proportion of SGA infants have extreme PWRs than AGA and LGA, especially
      at lower gestational ages. On average, SGA infants had higher PWRs than AGA and
      LGA infants. The overall curves offer population standards for use in research
      studies. The curves stratified by fetal growth adequacy are the first of their
      kind, and they demonstrate that PWR differs for SGA and LGA infants. 

PMID- 24895499
TI  - Establishing reliable miRNA-cancer association network based on text-mining
      method.
AB  - Associating microRNAs (miRNAs) with cancers is an important step of understanding
      the mechanisms of cancer pathogenesis and finding novel biomarkers for cancer
      therapies. In this study, we constructed a miRNA-cancer association network
      (miCancerna) based on more than 1,000 miRNA-cancer associations detected from
      millions of abstracts with the text-mining method, including 226 miRNA families
      and 20 common cancers. We further prioritized cancer-related miRNAs at the
      network level with the random-walk algorithm, achieving a relatively higher
      performance than previous miRNA disease networks. Finally, we examined the top 5
      candidate miRNAs for each kind of cancer and found that 71% of them are confirmed
      experimentally. miCancerna would be an alternative resource for the cancer
      related miRNA identification. 

PMID- 24895500
TI  - Leaky vaccines protect highly exposed recipients at a lower rate: implications
      for vaccine efficacy estimation and sieve analysis.
AB  - "Leaky" vaccines are those for which vaccine-induced protection reduces infection
      rates on a per-exposure basis, as opposed to "all-or-none" vaccines, which reduce
      infection rates to zero for some fraction of subjects, independent of the number
      of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a
      higher effective rate than subjects with more exposures. This simple observation
      has serious implications for analysis methodologies that rely on the assumption
      that the vaccine effect is homogeneous across subjects. We argue and show through
      examples that this heterogeneous vaccine effect leads to a violation of the
      proportional hazards assumption, to incomparability of infected cases across
      treatment groups, and to nonindependence of the distributions of the competing
      failure processes in a competing risks setting. We discuss implications for
      vaccine efficacy estimation, correlates of protection analysis, and mark-specific
      efficacy analysis (also known as sieve analysis). 

PMID- 24895501
TI  - RETRACTED ARTICLE: Radiation sialadenitis induced by high-dose radioactive iodine
      therapy.
AB  - Radioactive iodine ((131)I) is accumulated in the thyroid tissue and plays an
      important role in the treatment of differentiated papillary and follicular
      cancers after thyroidectomy. Simultaneously, (131)I is concentrated in the
      salivary glands and secreted into the saliva. Dose-related damage to the salivary
      parenchyma results from the (131)I irradiation. Salivary gland swelling and pain,
      usually involving the parotid, can be seen. The symptoms may develop immediately
      after a therapeutic dose of (131)I and/or months later and progress in intensity
      with time. In conjunction with the radiation sialadenitis, secondary
      complications reported include xerostomia, taste alterations, infection,
      increases in caries, facial nerve involvement, candidiasis, and neoplasia.
      Prevention of (131)I sialadenitis may involve the use of sialogogic agents to
      hasten the transit time of the radioactive iodine through the salivary glands.
      However, studies are not available to delineate the efficacy of this approach.
      Treatment of the varied complications that may develop encompass numerous
      approaches and include gland massage, sialogogic agents, duct probing,
      antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently
      interventional sialoendoscopy has been introduced an effective tool for the
      management of patients with (131)I-induced sialadenitis that is unresponsive to
      medical treatment. 

PMID- 24895502
TI  - In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha
      fetoprotein-producing hepatocellular carcinoma by targeted sodium iodide
      symporter gene expression.
AB  - PURPOSE: This study aimed to develop a gene expression targeting method for
      specific imaging and therapy of alpha-fetoprotein (AFP)-producing hepatocellular
      carcinoma (HCC) cells, using an adenovirus vector containing the human
      sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter. METHODS:
      The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by
      human AFP enhancer/promoter) was prepared. After in vitro infection by the
      adenovirus, hNIS gene expression in AFP-producing cells and in AFP-nonproducing
      cells was investigated using (125)I uptake assay and semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR). The killing effect of (131)I on
      AdAFPhNIS-infected HCC cells was studied using an in vitro clonogenic assay. In
      addition, tumor-bearing mice were intravenously injected with the adenovirus, and
      scintigraphic images were obtained. RESULTS: The expression of hNIS was
      efficiently demonstrated by (125)I uptake assay in AFP-producing cells, but not
      in AFP-nonproducing cells. AFP-producing HCC-targeted gene expression was
      confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that
      hNIS gene expression induced by AdAFPhNIS infection in AFP-producing cells caused
      more sensitivity to (131)I than that in AFP-nonproducing cells. Injected
      intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS
      gene expression was confirmed in tumor by in vivo scintigraphic imaging.
      CONCLUSIONS: An AFP-producing HCC was targeted with an adenovirus vector
      containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo.
      These findings demonstrate that AFP-producing HCC-specific molecular imaging and
      radionuclide gene therapy are feasible using this recombinant adenovirus vector
      system.

PMID- 24895503
TI  - Photo-guided sentinel node mapping in breast cancer using marker-free photo-gamma
      fusion lymphoscintigraphy.
AB  - PURPOSE: Photo-gamma fusion lymphoscintigraphy (PGFLS) was developed by overlying
      a conventional planar gamma image on a photograph for the guidance of sentinel
      node biopsy. The feasibility and accuracy of PGFLS was assessed in breast cancer
      patients. METHODS: A digital camera and a gamma camera were coordinated to obtain
      photograph and gamma images from the same angle. Using the distance to the object
      and calibration acquisition with a flat phantom and radioactive markers, PGFLS
      was performed both in phantom and in patients without fiducial markers. Marker
      free PGFLS was verified using flat phantom, anthropomorphic phantom with markers
      simulating sentinel nodes and breast cancer patients. In addition, the depth of
      the radioactive marker or sentinel node was calculated using two gamma images
      taken at right angles. The feasibility and accuracy of PGFLS were assessed in
      terms of mismatch errors of co-registration and depth with reference to the data
      from SPECT/CT. RESULTS: The mismatch error was less than 6 mm in the flat phantom
      image at a distance from 50 to 62 cm without misalignment. In the anthropomorphic
      phantom study, co-registration error was 0.42 +/- 0.29 cm; depth error was 0.51
      +/- 0.37 cm, which was well correlated with the reference value on SPECT/CT (x
      scale: R(2) = 0.99, p < 0.01; y scale: R(2) = 0.99, p < 0.01; depth: R(2) = 0.99,
      p < 0.01). In ten patients with breast cancer referred for lympho-SPECT/CT, PGFSL
      enabled photo-guided sentinel lymph node mapping with acceptable accuracy (co
      registration error, 0.47 +/- 0.24 cm; depth error, 1.20 +/-0.41 cm). The results
      from PGFSL showed close correlation with those from SPECT/CT (x scale: R(2) =
      0.99, p < 0.01; y scale: R(2) = 0.98, p < 0.01; depth: R(2) = 0.77, p < 0.01).
      CONCLUSIONS: The novel and convenient PGFLS technique is clinically feasible,
      showing acceptable accuracy and providing additional visual and quantitative
      information for sentinel lymph node mapping. This approach will facilitate photo
      guided sentinel lymph node dissection in breast cancer.

PMID- 24895504
TI  - Diagnostic Performance of Breast-Specific Gamma Imaging (BSGI) for Breast Cancer:
      Usefulness of Dual-Phase Imaging with (99m)Tc-sestamibi.
AB  - PURPOSE: The aim of this study was to investigate the usefulness of breast
      specific gamma imaging (BSGI) with dual-phase imaging for increasing diagnostic
      performance and interpreter confidence. METHODS: We studied 76 consecutive
      patients (mean age: 49.3 years, range: 33-61 years) who received 925 MBq (25 mCi)
      (99m)Tc-sestamibi intravenously. Craniocaudal and mediolateral oblique planar
      images were acquired for all patients. Delayed images were obtained from all
      patients 1 h after tracer injection, except for patients with no definite
      abnormal uptake. All images were classified into four categories: group 1
      (definite negative) = no definite abnormal uptake; group 2 (possible negative) =
      symmetrically diffuse and amorphous uptake; group 3 (possible positive) =
      asymmetrically mild and nodular uptake; group 4 (definite positive) =
      asymmetrically intense and nodular uptake. To evaluate diagnostic performance,
      the BSGI studies were classified as positive (group 3 or 4) or negative (group 1
      or 2) for malignancy according to a visual analysis. The final diagnoses were
      derived from histopathological confirmation and/or imaging follow-up after at
      least 6 months (range: 6-14 months) by both ultrasonography and mammography.
      RESULTS: The patients' ages ranged from 33 to 61 years, with an average of 49.3
      years. Thirteen patients were diagnosed with malignancy, and 63 patients were
      diagnosed as negative for malignancy. Using early images, 43 patients were
      classified as group 1, 12 as group 2, 10 as group 3 and 11 as group 4. Based on
      early images, the sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV) and accuracy of BSGI were 77 %, 83 %, 48 %, 95 %
      and 82 %, respectively. Dual-phase BSGI had a sensitivity, specificity, PPV, NPV
      and accuracy of 69 %, 95 %, 75 %, 94 % and 91 %, respectively. The BSGI
      specificity was significantly higher with dual-phase imaging than with single
      phase imaging (p = 0.0078), but the sensitivity did not differ significantly (p =
      1.0). Based on dual-phase imaging, the sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy of BSGI for the
      evaluation of US BI-RADS 4 lesions were 60 %, 86 %, 67 %, 83 % and 78 %,
      respectively. CONCLUSION: Dual-phase imaging in BSGI showed good diagnostic
      performance and would be useful for increasing interpreter diagnostic confidence,
      with higher specificity, positive predictive value and accuracy for breast cancer
      screening as well as the differential diagnosis of breast disease compared with
      single-phase imaging.

PMID- 24895454
TI  - Efficacy and safety of rivaroxaban compared with warfarin among elderly patients
      with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct
      Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke
      and Embolism Trial in Atrial Fibrillation (ROCKET AF).
AB  - BACKGROUND: Nonvalvular atrial fibrillation is common in elderly patients, who
      face an elevated risk of stroke but difficulty sustaining warfarin treatment. The
      oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the
      Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K
      Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation
      (ROCKET AF). This prespecified secondary analysis compares outcomes in older and
      younger patients. METHODS AND RESULTS: There were 6229 patients (44%) aged >=75
      years with atrial fibrillation and >=2 stroke risk factors randomized to warfarin
      (target international normalized ratio=2.0-3.0) or rivaroxaban (20 mg daily; 15
      mg if creatinine clearance <50 mL/min), double blind. The primary end point was
      stroke and systemic embolism by intention to treat. Over 10 866 patient-years,
      older participants had more primary events (2.57% versus 2.05%/100 patient-years;
      P=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P<0.0001).
      Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban
      versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence
      interval, 0.63-1.02) and younger patients (2.00% versus 2.10%/100 patient-years;
      hazard ratio=0.95; 95% confidence interval, 0.76-1.19; interaction P=0.313), as
      were major bleeding rates (>=75 years: 4.86% rivaroxaban versus 4.40% warfarin
      per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92-1.34; <75
      years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence
      interval, 0.78-1.19; interaction P=0.336). Hemorrhagic stroke rates were similar
      in both age groups; there was no interaction between age and rivaroxaban
      response. CONCLUSIONS: Elderly patients had higher stroke and major bleeding
      rates than younger patients, but the efficacy and safety of rivaroxaban relative
      to warfarin did not differ with age, supporting rivaroxaban as an alternative for
      the elderly.

PMID- 24895506
TI  - Usefulness of Combined Metabolic-Volumetric Indices of (18)F-FDG PET/CT for the
      Early Prediction of Neoadjuvant Chemotherapy Outcomes in Breast Cancer.
AB  - PURPOSE: The purpose of this study was to investigate the usefulness of metabolic
      volumetric indices of (18)F- fluorodeoxy-D-glucose ((18)F-FDG) positron emission
      tomography/computed tomography (PET/CT) for the evaluation of neoadjuvant
      chemotherapy outcomes in breast cancer. METHODS: Twenty-four patients with
      locally advanced breast cancer were enrolled in the study. They underwent
      baseline (18)F-FDG PET/CT scan and received four or six cycles of neoadjuvant
      chemotherapy, interim (18)F-FDG PET/CT was done after second cycle of
      chemotherapy. Maximum standardized uptake value (SUVmax), metabolic tumor volume
      (MTV), and total lesion glycolysis (TLG) of the primary lesions were calculated.
      Reduction rates of these parameters were obtained between baseline and interim
      (18)F-FDG PET/CT. Chemotherapy outcomes were assessed using tumor size reduction
      rate and histological grading system (Miller and Payne system). Reduction rates
      of SUVmax, MTV, and TLG correlated with chemotherapy outcomes. RESULTS: MTV and
      TLG reduction rates showed significant correlation with tumor size reduction rate
      (R = 0.68, P = 0.0004; R = 0.62, P = 0.002, respectively). However, SUVmax
      reduction rate showed no significant correlation. MTV and TLG reduction rates
      were significantly higher in responders than nonresponders, as determined by
      Miller and Payne system (P < 0.0007, P < 0.002). However, SUVmax reduction rate
      showed no significant difference. On ROC analysis, the area under the MTV and TLG
      curves was 0.886, and that of SUVmax was 0.743. Sensitivity, specificity,
      positive predictive value, and negative predictive value to predict
      histopathologic response were the same for MTV and TLG, and the values were 100
      %, 85.7 %, 83.3 %, and 100 %, respectively (at the reduction rate of 93.2 % for
      MTV, and 95.8 % for TLG). CONCLUSION: Changes of metabolic-volumetric indices
      successfully reflected the neoadjuvant chemotherapy outcomes. MTV and TLG could
      be robust indices in discriminating pathologic responder as SUVmax, after
      neoadjuvant chemotherapy.

PMID- 24895505
TI  - Usefulness of (18)F-fluoride PET/CT in Breast Cancer Patients with Osteosclerotic
      Bone Metastases.
AB  - PURPOSE: Bone metastasis is an important factor for the treatment and prognosis
      of breast cancer patients. Whole-body bone scintigraphy (WBBS) can evaluate
      skeletal metastases, and (18)F-FDG PET/CT seems to exhibit high specificity and
      accuracy in detecting bone metastases. However, there is a limitation of (18)F
      FDG PET in assessing sclerotic bone metastases because some lesions may be
      undetectable. Recent studies showed that (18)F-fluoride PET/CT is more sensitive
      than WBBS in detecting bone metastases. This study aims to evaluate the
      usefulness of (18)F-fluoride PET/CT by comparing it with WBBS and (18)F-FDG
      PET/CT in breast cancer patients with osteosclerotic skeletal metastases.
      MATERIALS AND METHODS: Nine breast cancer patients with suspected bone metastases
      (9 females; mean age +/- SD, 55.6 +/- 10.0 years) underwent (99m)Tc-MDP WBBS,
      (18)F-FDG PET/CT and (18)F-fluoride PET/CT. Lesion-based analysis of five regions
      of the skeletons (skull, vertebral column, thoracic cage, pelvic bones and long
      bones of extremities) and patient-based analysis were performed. RESULTS: (18)F
      fluoride PET/CT, (18)F-FDG PET/CT and WBBS detected 49, 20 and 25 true
      metastases, respectively. Sensitivity, specificity, positive predictive value and
      negative predictive value of (18)F-fluoride PET/CT were 94.2 %, 46.3 %, 57.7 %
      and 91.2 %, respectively. Most true metastatic lesions on (18)F-fluoride PET/CT
      had osteosclerotic change (45/49, 91.8 %), and only four lesions showed
      osteolytic change. Most lesions on (18)F-FDG PET/CT also demonstrated
      osteosclerotic change (17/20, 85.0 %) with three osteolytic lesions. All true
      metastatic lesions detected on WBBS and (18)F-FDG PET/CT were identified on (18)F
      fluoride PET/CT. CONCLUSION: (18)F-fluoride PET/CT is superior to WBBS or (18)F
      FDG PET/CT in detecting osteosclerotic metastatic lesions. (18)F-fluoride PET/CT
      might be useful in evaluating osteosclerotic metastases in breast cancer
      patients.

PMID- 24895508
TI  - Ovarian teratoma mimicking metastasis on I-131 scan : a case report.
AB  - The whole body I-131 scan is routinely performed in the postoperative treatment
      of patients with well-differentiated thyroid cancer. Accurate interpretation of
      whole body I-131 scan after thyroidectomy is critical to appropriate management
      of patients with thyroid cancer, to prevent unnecessary surgical removal or
      exposure to radioiodine. Unfortunately, false-positive uptakes in several other
      organs and their associated disease processes have been reported. We report a
      case of false-positive iodine uptake in the pelvic region with incidentally
      diagnosed mature cystic teratoma. 

PMID- 24895507
TI  - Differential Diagnosis of Parkinsonism Using Dual-Phase F-18 FP-CIT PET Imaging.
AB  - PURPOSE: Dopamine transporter (DAT) imaging can demonstrate presynaptic
      dopaminergic neuronal loss in Parkinson's disease (PD). However, differentiating
      atypical parkinsonism (APD) from PD is often difficult. We investigated the
      usefulness of dual-phase F-18 FP-CIT positron emission tomography (PET) imaging
      in the differential diagnosis of parkinsonism. METHODS: Ninety-eight subjects
      [five normal, seven drug-induced parkinsonism (DIP), five essential tremor (ET),
      24 PD, 20 multiple system atrophy-parkinson type (MSA-P), 13 multiple system
      atrophy-cerebellar type (MSA-C), 13 progressive supranuclear palsy (PSP), and 11
      dementia with Lewy bodies (DLB)] underwent F-18 FP-CIT PET. PET images were
      acquired at 5 min (early phase) and 3 h (late phase) after F-18 FP-CIT
      administration (185 MBq). Regional uptake pattern of cerebral and cerebellar
      hemispheres was assessed on early phase images and striatal DAT binding pattern
      was assessed on late phase images, using visual, quantitative, and statistical
      parametric mapping (SPM) analyses. RESULTS: Striatal DAT binding was normal in
      normal, ET, DIP, and MSA-C groups, but abnormal in PD, MSA-P, PSP, and DLB
      groups. No difference was found in regional uptake on early phase images among
      normal DAT binding groups, except in the MSA-C group. Abnormal DAT binding groups
      showed different regional uptake pattern on early phase images compared with PD
      in SPM analysis (FDR < 0.05). When discriminating APD from PD, visual
      interpretation of the early phase image showed high diagnostic sensitivity and
      specificity (75.4 % and 100 %, respectively). Regarding the ability to
      distinguish specific APD, sensitivities were 81 % for MSA-P, 77 % for MSA-C, 23 %
      for PSP, and 54.5 % for DLB. CONCLUSIONS: Dual-phase F-18 FP-CIT PET imaging is
      useful in demonstrating striatal DAT loss in neurodegenerative parkinsonism, and
      also in differentiating APD, particularly MSA, from PD.

PMID- 24895509
TI  - Paraneoplastic Cerebellar Degeneration as Initial Presentation of Papillary
      Carcinoma of the Fallopian Tube: Evaluation and Usefulness of (18)F-FDG PET-CT.
      Case Report and Literature Review.
AB  - The acquisition of an (18)F-FDG PET-CT scan in patients with suspected
      paraneoplastic cerebellar syndrome can be helpful in determining the origin of a
      neoplasm because of its high sensitivity and also helps guide the neurological
      development course depending on the degree of incorporation of (18)F-FDG to the
      cerebellar parenchyma when compared with the rest of the brain. 

PMID- 24895510
TI  - Bone Scan and SPECT/CT Findings in Marble Bone Disease.

PMID- 24895512
TI  - Pelvic Congestion Syndrome Initially Detected by Contrast-Enhanced F-18 FDG
      PET/CT.

PMID- 24895511
TI  - (18)F-FDG PET-CT for Detection of Recurrent Spinal Ependymoma.

PMID- 24895513
TI  - Simultaneous adrenal pheochromocytoma and carotid body paraganglioma in a woman.

PMID- 24895514
TI  - Usefulness of (18)F-FDG PET/CT in Evaluating Disease Activity at Different Times
      in a Patient With Chronic Periaortitis.

PMID- 24895515
TI  - Retraction note: Radiation sialadenitis induced by high-dose radioactive iodine
      therapy.

PMID- 24895516
TI  - Computational Framework for Determining Patient-Specific Total Knee Arthroplasty
      Loading.
AB  - The purpose of this work is to describe a computational framework for predicting
      total knee arthroplasty loads which are necessary for accurate preclinical
      testing of implant designs. Inputs required include patient knee joint
      kinematics, and implant type, size, and physiological alignment. Computational
      models used in the framework include the calculation of knee joint kinematics and
      kinetics, prediction of the contact path, a model to determine muscle forces, and
      a force model to obtain parametric solutions for implant forces. The resulting
      knee implant forces have been validated in two studies, and in both the model
      accurately predicted differences in knee joint loading. To date, implant contact
      forces have been predicted for 35 patients with four different implant types.
      Forces have been calculated for walking, chair, and stair activities.

PMID- 24895517
TI  - Blood Damage Quantification in Cardiovascular Flows Through Medical Devices Using
      a Novel Suspension Flow Method.

PMID- 24895518
TI  - Open Knee: A Pathway to Community Driven Modeling and Simulation in Joint
      Biomechanics.

PMID- 24895519
TI  - Simulating the Dynamics of an Aortic Valve Prosthesis in a Pulse Duplicator:
      Numerical Methods and Initial Experience.

PMID- 24895520
TI  - Patient-Specific Finite Element Simulations of Standard Incisional Astigmatism
      Surgery and a Novel Patterned Collagen Crosslinking Approach to Astigmatism
      Treatment.

PMID- 24895521
TI  - Tesla-Based Blood Pump and Its Applications.

PMID- 24895522
TI  - Hemodynamic Impact of Transcatheter Aortic Valve Deployment Configuration.

PMID- 24895523
TI  - The Vascular Model Repository: A Public Resource of Medical Imaging Data and
      Blood Flow Simulation Results.
AB  - Patient-specific blood flow simulations may provide insight into disease
      progression, treatment options, and medical device design that would be difficult
      or impossible to obtain experimentally. However, publicly available image data
      and computer models for researchers and device designers are extremely limited.
      The National Heart, Lung, and Blood Institute sponsored Open Source Medical
      Software Corporation (contract nos. HHSN268200800008C and HHSN268201100035C) and
      its university collaborators to build a repository (www.vascularmodel.org)
      including realistic, image-based anatomic models and related hemodynamic
      simulation results to address this unmet need.

PMID- 24895524
TI  - Modeling the Role of Oscillator Flow and Dynamic Mechanical Conditioning on Dense
      Connective Tissue Formation in Mesenchymal Stem Cell-Derived Heart Valve Tissue
      Engineering.

PMID- 24895525
TI  - Effects of heat acclimation on changes in oxidative stress and inflammation
      caused by endurance capacity test in the heat.
AB  - BACKGROUND: The aim was to determine the effect of heat acclimation (HA) on
      oxidative stress (OxS) and inflammation in resting conditions and on the response
      pattern of these parameters to exhausting endurance exercise. METHODS: Parameters
      of OxS and inflammation were measured in non-heat-acclimated status (NHAS) and
      after a 10-day HA program (i.e., in heat-acclimated status; HAS) both at baseline
      and after an endurance capacity (EC) test in the heat. RESULTS: As a result of
      HA, EC increased from 88.62 +/- 27.51 to 161.95 +/- 47.80 minutes (P < 0.001). HA
      increased OxS level: total peroxide concentration rose from 219.38 +/- 105.18 to
      272.57 +/- 133.39  MUmol/L (P < 0.05) and oxidative stress index (OSI) from 14.97
      +/- 8.24 to 20.46 +/- 11.13% (P < 0.05). In NHAS, the EC test increased OxS
      level: total peroxide concentration rose from 219.38 +/- 105.18 to 278.51 +/-
      125.76  MUmol/L (P < 0.001) and OSI from 14.97 +/- 8.24 to 19.31 +/- 9.37% (P <
      0.01). However, in HAS, the EC test reduced OSI from 20.46 +/- 11.13 to 16.83 +/-
      8.89% (P < 0.05). The value of log high-sensitive C-reactive protein increased
      from -0.32 +/- 0.32 to -0.12 +/- 0.34 mg/L (P < 0.05) in NHAS and from -0.31 +/-
      0.47 to 0.28 +/- 0.46 mg/L (P < 0.001) in HAS. CONCLUSION: HA increases OxS
      level. However, beneficial adaptive effects of HA on acute exhaustive exercise
      induced changes in OxS and inflammation parameters occur in a hot environment.

PMID- 24895526
TI  - Resveratrol counteracts inflammation in human M1 and M2 macrophages upon
      challenge with 7-oxo-cholesterol: potential therapeutic implications in
      atherosclerosis.
AB  - MACROPHAGES CONSIST OF TWO MAIN SUBSETS: the proinflammatory M1 subset and the
      anti-inflammatory M2 one. 7-oxo-cholesterol, the most abundant cholesterol
      autoxidation product within atherosclerotic plaque, is able to skew the M1/M2
      balance towards a proinflammatory profile. In the present study, we explored the
      ability of the polyphenolic compound resveratrol to counteract the 7-oxo
      cholesterol-triggered proinflammatory signaling in macrophages. Resveratrol
      pretreated human monocyte-derived M1 and M2 macrophages were challenged with 7
      oxo-cholesterol and analyzed for phenotype and endocytic ability by flow
      cytometry, for metalloproteinase- (MMP-) 2 and MMP-9 by gelatin zymography, and
      for cytokine, chemokine, and growth factor secretome by a multiplex immunoassay.
      We also investigated the NF-kappaB signaling pathway. In the M1 subset,
      resveratrol prevented the downregulation of CD16 and the upregulation of MMP-2 in
      response to 7-oxo-cholesterol, whereas in M2 macrophages it prevented the
      upregulation of CD14, MMP-2, and MMP-9 and the downregulation of endocytosis.
      Resveratrol prevented the upregulation of several proinflammatory and
      proangiogenic molecules in both subsets. We identified modulation of NF-kappaB as
      a potential mechanism implicated in 7-oxo-cholesterol and resveratrol effects.
      Our results strengthen previous findings on the immunomodulatory ability of
      resveratrol and highlight its role as potential therapeutic or preventive
      compound, to counteract the proatherogenic oxysterol signaling within
      atherosclerotic plaque.

PMID- 24895527
TI  - Insulin regulates glucose consumption and lactate production through reactive
      oxygen species and pyruvate kinase M2.
AB  - Although insulin is known to regulate glucose metabolism and closely associate
      with liver cancer, the molecular mechanisms still remain to be elucidated. In
      this study, we attempt to understand the mechanism of insulin in promotion of
      liver cancer metabolism. We found that insulin increased pyruvate kinase M2
      (PKM2) expression through reactive oxygen species (ROS) for regulating glucose
      consumption and lactate production, key process of glycolysis in hepatocellular
      carcinoma HepG2 and Bel7402 cells. Interestingly, insulin-induced ROS was found
      responsible for the suppression of miR-145 and miR-128, and forced expression of
      either miR-145 or miR-128 was sufficient to abolish insulin-induced PKM2
      expression. Furthermore, the knockdown of PKM2 expression also inhibited cancer
      cell growth and insulin-induced glucose consumption and lactate production,
      suggesting that PKM2 is a functional downstream effecter of insulin. Taken
      together, this study would provide a new insight into the mechanism of insulin
      induced glycolysis. 

PMID- 24895530
TI  - Real-Time Estimation of Glenohumeral Joint Rotation Center With Cable-Driven Arm
      Exoskeleton (CAREX)-A Cable-Based Arm Exoskeleton.
AB  - In the past few years, the authors have proposed several prototypes of a Cable
      driven upper ARm EXoskeleton (CAREX) for arm rehabilitation. One of the
      assumptions of CAREX was that the glenohumeral joint rotation center (GH-c)
      remains stationary in the inertial frame during motion, which leads to inaccuracy
      in the kinematic model and may hamper training performance. In this paper, we
      propose a novel approach to estimate GH-c using measurements of shoulder joint
      angles and cable lengths. This helps in locating the GH-c center appropriately
      within the kinematic model. As a result, more accurate kinematic model can be
      used to improve the training of human users. An estimation algorithm is presented
      to compute the GH-c in real-time. The algorithm was implemented on the latest
      prototype of CAREX. Simulations and preliminary experimental results are
      presented to validate the proposed GH-c estimation method.

PMID- 24895528
TI  - Nrf2 deficiency exaggerates doxorubicin-induced cardiotoxicity and cardiac
      dysfunction.
AB  - The anticancer therapy of doxorubicin (Dox) has been limited by its acute and
      chronic cardiotoxicity. In addition to a causative role of oxidative stress,
      autophagy appears to play an important role in the regulation of Dox-induced
      cardiotoxicity. However, the underlying mechanisms remain unclear. Accordingly,
      we explored a role of nuclear factor erythroid-2 related factor 2 (Nrf2) in Dox
      induced cardiomyopathy with a focus on myocardial oxidative stress and autophagic
      activity. In wild type (WT) mice, a single intraperitoneal injection of 25 mg/kg
      Dox rapidly induced cardiomyocyte necrosis and cardiac dysfunction, which were
      associated with oxidative stress, impaired autophagy, and accumulated
      polyubiquitinated protein aggregates. However, these Dox-induced adverse effects
      were exaggerated in Nrf2 knockout (Nrf2(-/-)) mice. In cultured cardiomyocytes,
      overexpression of Nrf2 increased the steady levels of LC3-II, ameliorated Dox
      induced impairment of autophagic flux and accumulation of ubiquitinated protein
      aggregates, and suppressed Dox-induced cytotoxicity, whereas knockdown of Nrf2
      exerted opposite effects. Moreover, the exaggerated adverse effects in Dox
      intoxicated Nrf2 depleted cardiomyocytes were dramatically attenuated by forced
      activation of autophagy via overexpression of autophagy related gene 5 (Atg5).
      Thus, these results suggest that Nrf2 is likely an endogenous suppressor of Dox
      induced cardiotoxicity by controlling both oxidative stress and autophagy in the
      heart. 

PMID- 24895531
TI  - Point-of-Care Tests for HIV, Related Coinfections, and Blood-Borne Infections.

PMID- 24895529
TI  - Piperlongumine induces apoptosis and synergizes with cisplatin or paclitaxel in
      human ovarian cancer cells.
AB  - Piperlongumine (PL), a natural alkaloid from Piper longum L., possesses the
      highly selective and effective anticancer property. However, the effect of PL on
      ovarian cancer cells is still unknown. In this study, we firstly demonstrate that
      PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore,
      PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the
      intracellular reactive oxidative species (ROS) in a dose- and time-dependent
      manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse
      the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of
      PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth
      effect on human ovarian cancer cells. Collectively, our study provides new
      therapeutic potential of PL on human ovarian cancer. 

PMID- 24895532
TI  - Prognostic factors in tuberculosis related mortalities in hospitalized patients.
AB  - Setting. The study was undertaken at the Department of Pulmonology at a public,
      tertiary care centre in Karachi, Pakistan. Objectives. To evaluate factors
      concerned with in-hospital deaths in patients admitted with pulmonary
      tuberculosis (TB). Design. A retrospective case-control audit was performed for
      120 patients hospitalised with pulmonary TB. Sixty of those discharged after
      treatment were compared to sixty who did not survive. Radiological findings,
      clinical indicators, and laboratory values were compared between the two groups
      to identify factors related to poor prognosis. Results. Factors concerned with in
      hospital mortality listed late presentation of disease (P < 0.01), noncompliance
      to antituberculosis therapy (P < 0.01), smoking (P < 0.01), longer duration of
      illness prior to treatment (P < 0.01), and low body weight (P < 0.01). Most
      deaths occurred during the first week of admission (P < 0.01) indicating late
      referrals as significant. Immunocompromised status and multi-drug resistance were
      not implicated in higher mortality. Conclusions. Poor prognosis was associated
      with noncompliance to therapy resulting in longer duration of illness, late
      patient referrals to care centres, and development of complications. Early
      diagnosis, timely referrals, and monitored compliance may help reduce mortality.
      Adherence to a more radically effective treatment regimen is required to
      eliminate TB early during disease onset. 

PMID- 24895533
TI  - Intra-Articular Analgesia and Steroid Reduce Pain Sensitivity in Knee OA
      Patients: An Interventional Cohort Study.
AB  - Objectives. To assess the effects of intra-articular therapy on pain sensitivity
      in the knee and surrounding tissues in knee OA patients. Methods. Twenty-five
      knee OA patients with symptomatic knee OA were included in this interventional
      cohort study. Pressure pain thresholds (PPT) were recorded before, immediately
      after, and two weeks after ultrasound guided intra-articular injection of
      lidocaine combined with glucocorticosteroid. Computer-controlled and manual
      pressure algometers were used to assess PPT on the knee, vastus lateralis,
      tibialis anterior, and the extensor carpi radialis longus muscles (control site).
      Results. Significantly increased PPTs were found following intra-articular
      injection, at both the knee (P < 0.0001) and the surrounding muscles (P < 0.042).
      The treatment effects were sustained for two weeks, and at some points the effect
      was even greater at two weeks (P < 0.026). Albeit not statistically significant,
      a similar trend was observed at the control site. Conclusions. Intra-articular
      anesthesia, combined with glucocorticosteroid, reduced pain sensitivity in both
      the knee and surrounding muscles for at least two weeks. 

PMID- 24895534
TI  - Parent training interventions for toddlers with autism spectrum disorder.
AB  - Background. Now that early identification of toddlers with autism spectrum
      disorder (ASD) is possible, efforts are being made to develop interventions for
      children under three years of age. Most studies on early intervention have
      focused on intensive and individual interventions. However, parent training
      interventions that help parents interact and communicate with their toddlers with
      ASD might be a good alternative to promote the development of their child's
      sociocommunicative skills. Objective. This review aims to systematically examine
      (1) the use of parent training interventions for children with ASD under three
      years of age and (2) their effects on children's development, parents' well-being
      and parent-child interactions. Methods. Systematic searches were conducted to
      retrieve studies in which at least one parent was trained to implement ASD
      specific techniques with their toddlers (0-36 months old) with a diagnosis of or
      suspected ASD. Results. Fifteen studies, involving 484 children (mean age: 23.26
      months), were included in this review. Only two of them met criteria for
      conclusive evidence. Results show that parents were able to implement newly
      learned strategies and were generally very satisfied with parent training
      programs. However, findings pertaining to the children's communication and
      socioemotional skills, parent-child interactions, and parental well-being were
      inconclusive. 

PMID- 24895535
TI  - Treatment of nongout joint deposition diseases: an update.
AB  - This update develops the actual therapeutic options in the management of the
      joint involvement of calcium pyrophosphate deposition disease (CPPD), basic
      calcium phosphate (BCP) deposition disease, hemochromatosis (HH), ochronosis,
      oxalosis, and Wilson's disease. Conventional pharmaceutical treatment provides
      benefits for most diseases. Anti-interleukine-1 (IL-1) treatment could provide
      similar results in CPPD than in gout flares. There is only limited evidence about
      the efficacy of preventive long-term colchicine intake, methotrexate, and
      hydroxychloroquine in chronic CPPD. Needle aspiration and lavage have
      satisfactory short and midterm results in BCP. Extracorporeal shockwave therapy
      has also proved its efficacy for high-doses regimes. Phlebotomy does not seem to
      have shown real efficacy on joint involvement in HH so far. Iron chelators'
      effects have not been assessed on joint involvement either, while IL-1 blockade
      may prove useful. NSAIDs have limited efficacy on joint involvement of oxalosis,
      while colchicine and steroids have not been assessed either. The use of
      nitisinone for ochronotic arthropathy is still much debated, but it could provide
      beneficial effects on joint involvement. The effects of copper chelators have not
      been assessed either in the joint involvement of Wilson's disease. NSAIDs should
      be avoided because of the liver affection they may worsen. 

PMID- 24895539
TI  - Relationships between Obstructive Sleep Apnea Syndrome, Continuous Positive
      Airway Pressure Treatment, and Inflammatory Cytokines.
AB  - The cardiovascular complications that frequently accompany obstructive sleep
      apnea syndrome (OSAS) are thought to develop as a result of inflammatory stress
      associated with cytokines such as IL-6 and TNF- alpha . We conducted the current
      study to compare levels of these cytokines in OSAS patients (n = 33) and
      nonapneic controls (n = 24). Furthermore, we investigated the impact of a three
      month regime of continuous positive airway pressure (CPAP) on serum levels of IL
      6 and TNF- alpha only in the OSAS patients. There were no significant differences
      in serum levels of either IL-6 (P = 0.782) or TNF- alpha (P = 0.722) or TNF-
      alpha (P = 0.722) between OSAS patients and nonapneic controls. Serum IL-6 levels
      correlated significantly with neck circumference in OSAS patients (P = 0.006). In
      OSAS patients, reduced levels of TNF- alpha and IL-6 correlated with increases in
      mean SaO2 after CPAP treatment (P = 0.020 and P = 0.051, resp.). However, neither
      of cytokine levels was significantly impacted by CPAP therapy (both P > 0.137).
      We have demonstrated that plasma cytokine levels are similar in both otherwise
      healthy subjects with OSAS and in nonapneic control, and we conclude that OSAS
      related parameters and CPAP treatment do not play a significant role in altering
      cytokine levels. 

PMID- 24895538
TI  - Root canal morphology of permanent maxillary and mandibular canines in Indian
      population using cone beam computed tomography.
AB  - Aim. To investigate the root canal anatomy of single-rooted permanent maxillary
      and mandibular canines in an Indian population using cone beam computed
      tomography (CBCT). Methodology. A total of 250 permanent maxillary canines and
      250 permanent mandibular canines were selected and scanned using CBCT. The root
      anatomy of each tooth was evaluated for the following parameters: the pattern of
      the root canals, anatomic length of the crown and the root, the presence of
      accessory canals, the shape of the access cavity, the position of the apical
      foramina, root diameter, and dentin thickness of the root. Results. Majority of
      the teeth had a Type I canal configuration in both maxillary canines (81.6%) and
      mandibular canines (79.6%). In maxillary canine the other canal patterns found
      were Type III (11.6%), Type II (2.8%), Type V (2%), Type XIX (1.2%), and Type IV
      (0.8%). In mandibular canines the various other canal patterns found were Type
      III (13.6%), Type II (3.2%), Type V (2%), and Type XIX (1.6%). Apical foramina
      were laterally positioned in the majority of the teeth, 70.4% and 65.6% in
      maxillary and mandibular canines, respectively. 12% of the maxillary canines and
      12.8% of the mandibular canines had accessory canals. Conclusion. The root canal
      anatomy of permanent maxillary and mandibular canines varied widely in an Indian
      population. 

PMID- 24895537
TI  - Microbial tyrosinases: promising enzymes for pharmaceutical, food bioprocessing,
      and environmental industry.
AB  - Tyrosinase is a natural enzyme and is often purified to only a low degree and it
      is involved in a variety of functions which mainly catalyse the o-hydroxylation
      of monophenols into their corresponding o-diphenols and the oxidation of o
      diphenols to o-quinones using molecular oxygen, which then polymerizes to form
      brown or black pigments. The synthesis of o-diphenols is a potentially valuable
      catalytic ability and thus tyrosinase has attracted a lot of attention with
      respect to industrial applications. In environmental technology it is used for
      the detoxification of phenol-containing wastewaters and contaminated soils, as
      biosensors for phenol monitoring, and for the production of L-DOPA in
      pharmaceutical industries, and is also used in cosmetic and food industries as
      important catalytic enzyme. Melanin pigment synthesized by tyrosinase has found
      applications for protection against radiation cation exchangers, drug carriers,
      antioxidants, antiviral agents, or immunogen. The recombinant V. spinosum
      tryosinase protein can be used to produce tailor-made melanin and other
      polyphenolic materials using various phenols and catechols as starting materials.
      This review compiles the recent data on biochemical and molecular properties of
      microbial tyrosinases, underlining their importance in the industrial use of
      these enzymes. After that, their most promising applications in pharmaceutical,
      food processing, and environmental fields are presented. 

PMID- 24895536
TI  - Clinical causes of inflammation in peritoneal dialysis patients.
AB  - Inflammation at both systemic and local intraperitoneal levels commonly affects
      peritoneal dialysis (PD) patients. Interest in inflammatory markers as targets of
      therapeutic intervention has been considerable as they are recognised as
      predictors of poor clinical outcomes. However, prior to embarking on strategies
      to reduce inflammatory burden, it is of paramount importance to define the
      underlying processes that drive the chronic active inflammatory status. The
      present review aims to comprehensively describe clinical causes of inflammation
      in PD patients to which potential future strategies may be targeted. 

PMID- 24895540
TI  - Restless leg syndrome in diabetics compared with normal controls.
AB  - Introduction. Restless leg syndrome (RLS) is a common sleep disorder which is
      characterized by urge to move the legs accompanied by disturbing and
      uncomfortable leg sensation during night and rest. This common condition affects
      7-10% of general population and is frequently unrecognized, misdiagnosed, and
      poorly managed. Several clinical conditions like diabetes have been associated
      with secondary form of RLS. This study analyzed the frequency and possible risk
      factor for RLS development in diabetic patient. Material and Methods. This
      descriptive case-control study was done on 140 consecutive outpatient diabetics
      and age, sex, and body mass index matched control group. RLS was diagnosed by
      criteria of the International RLS Study Group. Results. Prevalence of RLS was
      28.6% in diabetes and 7.1% in control group (P = 0.001). Sex difference was not
      significant and with rising duration of diabetes prevalence of RLS was not
      increased. Discussion. With regarding significant association between RLS and
      diabetes and its negative impact on quality of life/health outcome/sleep/daytime
      activity/cognitive function/ and mental state of diabetic patient/higher
      awareness of RLS among physicians and related health worker suggested. 

PMID- 24895542
TI  - Serum copper and haematological values of sheep of different physiological stages
      in the dry and wet seasons of central trinidad.
AB  - A study was conducted to determine serum copper (Cu) concentrations and
      hematological values of 174 sheep from four medium sized farms, pertaining to
      physiological stage, in the late dry and late wet seasons of Central Trinidad.
      Serum Cu was significantly lower in the dry than in the wet season (P < 0.001)
      with a corresponding high percentage of samples with low Cu levels in the former.
      31% of dry nonpregnant sheep exhibited a nonregenerative anaemia. Also,
      hemoglobin and packed cell volume values varied (P < 0.001) including lymphocyte
      (P < 0.01) counts, among growing animals compared with other physiological
      stages. Significant variations also occurred among neutrophil (P < 0.05) and
      eosinophil (P < 0.05) values in sheep. Highest haemoglobin and packed cell
      volume, white blood cell counts, and lymphocyte values in growing sheep compared
      with other stages were probably age related. 

PMID- 24895541
TI  - Playing and listening to tailor-made notched music: cortical plasticity induced
      by unimodal and multimodal training in tinnitus patients.
AB  - BACKGROUND. The generation and maintenance of tinnitus are assumed to be based on
      maladaptive functional cortical reorganization. Listening to modified music,
      which contains no energy in the range of the individual tinnitus frequency, can
      inhibit the corresponding neuronal activity in the auditory cortex. Music making
      has been shown to be a powerful stimulator for brain plasticity, inducing changes
      in multiple sensory systems. Using magnetoencephalographic (MEG) and behavioral
      measurements we evaluated the cortical plasticity effects of two months of (a)
      active listening to (unisensory) versus (b) learning to play (multisensory)
      tailor-made notched music in nonmusician tinnitus patients. Taking into account
      the fact that uni- and multisensory trainings induce different patterns of
      cortical plasticity we hypothesized that these two protocols will have different
      affects. RESULTS. Only the active listening (unisensory) group showed significant
      reduction of tinnitus related activity of the middle temporal cortex and an
      increase in the activity of a tinnitus-coping related posterior parietal area.
      CONCLUSIONS. These findings indicate that active listening to tailor-made notched
      music induces greater neuroplastic changes in the maladaptively reorganized
      cortical network of tinnitus patients while additional integration of other
      sensory modalities during training reduces these neuroplastic effects.

PMID- 24895543
TI  - In Silico Prediction of T and B Cell Epitopes of Der f 25 in Dermatophagoides
      farinae.
AB  - The house dust mites are major sources of indoor allergens for humans, which
      induce asthma, rhinitis, dermatitis, and other allergic diseases. Der f 25 is a
      triosephosphate isomerase, representing the major allergen identified in
      Dermatophagoides farinae. The objective of this study was to predict the B and T
      cell epitopes of Der f 25. In the present study, we analyzed the physiochemical
      properties, function motifs and domains, and structural-based detailed features
      of Der f 25 and predicted the B cell linear epitopes of Der f 25 by DNAStar
      protean system, BPAP, and BepiPred 1.0 server and the T cell epitopes by
      NetMHCIIpan-3.0 and NetMHCII-2.2. As a result, the sequence and structure
      analysis identified that Der f 25 belongs to the triosephosphate isomerase family
      and exhibited a triosephosphate isomerase pattern (PS001371). Eight B cell
      epitopes (11-18, 30-35, 71-77, 99-107, 132-138, 173-187, 193-197, and 211-224)
      and five T cell epitopes including 26-34, 38-54, 66-74, 142-151, and 239-247 were
      predicted in this study. These results can be used to benefit allergen
      immunotherapies and reduce the frequency of mite allergic reactions. 

PMID- 24895544
TI  - Association between NFKB1 -94ins/del ATTG Promoter Polymorphism and Cancer
      Susceptibility: An Updated Meta-Analysis.
AB  - Nuclear factor- kappa B is associated with the pathogenesis of numerous
      malignancies, and the functional polymorphism -94ins/del ATTG (rs28362491) in the
      human NFKB1 gene is associated with cancer risk. Previous studies on the
      association between the -94ins/del ATTG polymorphism and cancer risk reported
      conflicting results. To clarify this relationship, we performed a meta-analysis
      of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled
      odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the
      association. We found that the NFKB1 promoter -94ins/del ATTG polymorphism was
      significantly associated with cancer risk in four genetic models (ins/ins versus
      del/del, OR = 1.47, 95% CI = 1.11-1.93; dominant model, OR = 1.26, 95% CI = 1.03
      1.53; recessive model, OR = 1.26, 95% CI = 1.05-1.51; ins allele versus del
      allele, OR = 1.19, 95% CI = 1.05-1.35). Stratified analyses revealed a
      significant association between the polymorphism and ovarian, oral, and prostate
      cancers. Similar results were determined in an Asian population and not in a
      Caucasian population. Thus, our results suggested that the polymorphism can
      contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer
      specific effects on cancer risk. Further large-scale and functional studies are
      necessary to elucidate this possible effect. 

PMID- 24895545
TI  - Identification and Expression Profiling of the BTB Domain-Containing Protein Gene
      Family in the Silkworm, Bombyx mori.
AB  - The BTB domain is a conserved protein-protein interaction motif. In this study,
      we identified 56 BTB domain-containing protein genes in the silkworm, in addition
      to 46 in the honey bee, 55 in the red flour beetle, and 53 in the monarch
      butterfly. Silkworm BTB protein genes were classified into nine subfamilies
      according to their domain architecture, and most of them could be mapped on the
      different chromosomes. Phylogenetic analysis suggests that silkworm BTB protein
      genes may have undergone a duplication event in three subfamilies: BTB-BACK
      Kelch, BTB-BACK-PHR, and BTB-FLYWCH. Comparative analysis demonstrated that the
      orthologs of each of 13 BTB protein genes present a rigorous orthologous
      relationship in the silkworm and other surveyed insects, indicating conserved
      functions of these genes during insect evolution. Furthermore, several silkworm
      BTB protein genes exhibited sex-specific expression in larval tissues or at
      different stages during metamorphosis. These findings not only contribute to a
      better understanding of the evolution of insect BTB protein gene families but
      also provide a basis for further investigation of the functions of BTB protein
      genes in the silkworm. 

PMID- 24895547
TI  - Double-bottom chaotic map particle swarm optimization based on chi-square test to
      determine gene-gene interactions.
AB  - Gene-gene interaction studies focus on the investigation of the association
      between the single nucleotide polymorphisms (SNPs) of genes for disease
      susceptibility. Statistical methods are widely used to search for a good model of
      gene-gene interaction for disease analysis, and the previously determined models
      have successfully explained the effects between SNPs and diseases. However, the
      huge numbers of potential combinations of SNP genotypes limit the use of
      statistical methods for analysing high-order interaction, and finding an
      available high-order model of gene-gene interaction remains a challenge. In this
      study, an improved particle swarm optimization with double-bottom chaotic maps
      (DBM-PSO) was applied to assist statistical methods in the analysis of associated
      variations to disease susceptibility. A big data set was simulated using the
      published genotype frequencies of 26 SNPs amongst eight genes for breast cancer.
      Results showed that the proposed DBM-PSO successfully determined two- to six
      order models of gene-gene interaction for the risk association with breast cancer
      (odds ratio > 1.0; P value <0.05). Analysis results supported that the proposed
      DBM-PSO can identify good models and provide higher chi-square values than
      conventional PSO. This study indicates that DBM-PSO is a robust and precise
      algorithm for determination of gene-gene interaction models for breast cancer. 

PMID- 24895546
TI  - Alteration of ROS homeostasis and decreased lifespan in S. cerevisiae elicited by
      deletion of the mitochondrial translocator FLX1.
AB  - This paper deals with the control exerted by the mitochondrial translocator FLX1,
      which catalyzes the movement of the redox cofactor FAD across the mitochondrial
      membrane, on the efficiency of ATP production, ROS homeostasis, and lifespan of
      S. cerevisiae. The deletion of the FLX1 gene resulted in respiration-deficient
      and small-colony phenotype accompanied by a significant ATP shortage and ROS
      unbalance in glycerol-grown cells. Moreover, the flx1Delta strain showed H2O2
      hypersensitivity and decreased lifespan. The impaired biochemical phenotype found
      in the flx1Delta strain might be justified by an altered expression of the
      flavoprotein subunit of succinate dehydrogenase, a key enzyme in bioenergetics
      and cell regulation. A search for possible cis-acting consensus motifs in the
      regulatory region upstream SDH1-ORF revealed a dozen of upstream motifs that
      might respond to induced metabolic changes by altering the expression of Flx1p.
      Among these motifs, two are present in the regulatory region of genes encoding
      proteins involved in flavin homeostasis. This is the first evidence that the
      mitochondrial flavin cofactor status is involved in controlling the lifespan of
      yeasts, maybe by changing the cellular succinate level. This is not the only case
      in which the homeostasis of redox cofactors underlies complex phenotypical
      behaviours, as lifespan in yeasts. 

PMID- 24895548
TI  - Iron (FeII) chelation, ferric reducing antioxidant power, and immune modulating
      potential of Arisaema jacquemontii (Himalayan Cobra Lily).
AB  - This study explored the antioxidant and immunomodulatory potential of
      ethnomedicinally valuable species, namely, Arisaema jacquemontii of north-western
      Himalayan region. The tubers, leaves, and fruits of this plant were subjected to
      extraction using different solvents. In vitro antioxidant studies were performed
      in terms of chelation power on ferrous ions and FRAP assay. The crude methanol
      extract of leaves was found to harbour better chelating capacity (58% at 100 MU
      g/mL) and reducing power (FRAP value 1085.4 +/- 0.11 MU MFe(3+)/g dry wt.) than
      all the other extracts. The crude methanol extract was thus further partitioned
      with solvents to yield five fractions. Antioxidant study of fractions suggested
      that the methanol fraction possessed significant chelation capacity (49.7% at 100
      MU g/mL) and reducing power with FRAP value of 1435.4 MU M/g dry wt. The
      fractions were also studied for immune modulating potential where it was observed
      that hexane fraction had significant suppressive effect on mitogen induced T-cell
      and B-cell proliferation and remarkable stimulating effect on humoral response by
      141% and on DTH response by 168% in immune suppressed mice as compared to the
      controls. Therefore, it can be concluded that A. jacquemontii leaves hold
      considerable antioxidant and immunomodulating potential and they can be explored
      further for the identification of their chemical composition for a better
      understanding of their biological activities.

PMID- 24895549
TI  - IDH1(R132H) mutation increases U87 glioma cell sensitivity to radiation therapy
      in hypoxia.
AB  - OBJECTIVE: IDH1 codon 132 mutation (mostly Arg132His) is frequently found in
      gliomas and is associated with longer survival. However, it is still unclear
      whether IDH1 mutation renders the cell more vulnerable to current treatment,
      radio- and chemotherapy. MATERIALS AND METHODS: We transduced U87 with wild type
      IDH1 or IDH1 (R132H) expressing lentivirus and analyzed the radiosensitivity
      (dose ranging 0 to 10 Gy) under normoxia (20% O2) and moderate hypoxia (1% O2).
      RESULTS: We observed that IDH1 (R132H) U87 cells grow faster in hypoxia and were
      more sensitive to radiotherapy (in terms of cell mortality and colony formation
      assay) compared to nontransduced U87 and IDH1 (wt) cells. This effect was not
      observed in normoxia. CONCLUSION: These data suggest that IDH1 (R132H) mutation
      increases radiosensitivity in mild hypoxic conditions.

PMID- 24895550
TI  - Prenatal maternal stress predicts childhood asthma in girls: project ice storm.
AB  - Little is known about how prenatal maternal stress (PNMS) influences risks of
      asthma in humans. In this small study, we sought to determine whether disaster
      related PNMS would predict asthma risk in children. In June 1998, we assessed
      severity of objective hardship and subjective distress in women pregnant during
      the January 1998 Quebec Ice Storm. Lifetime asthma symptoms, diagnoses, and
      corticosteroid utilization were assessed when the children were 12 years old (N =
      68). No effects of objective hardship or timing of the exposure were found.
      However, we found that, in girls only, higher levels of prenatal maternal
      subjective distress predicted greater lifetime risk of wheezing (OR = 1.11; 90%
      CI = 1.01-1.23), doctor-diagnosed asthma (OR = 1.09; 90% CI = 1.00-1.19), and
      lifetime utilization of corticosteroids (OR = 1.12; 90% CI = 1.01-1.25). Other
      perinatal and current maternal life events were also associated with asthma
      outcomes. Findings suggest that stress during pregnancy opens a window for fetal
      programming of immune functioning. A sex-based approach may be useful to examine
      how prenatal and postnatal environments combine to program the immune system.
      This small study needs to be replicated with a larger, more representative
      sample. 

PMID- 24895551
TI  - Potent protein glycation inhibition of plantagoside in Plantago major seeds.
AB  - Plantagoside (5,7,4',5'-tetrahydroxyflavanone-3'-O-glucoside) and its aglycone
      (5,7,3',4',5'-pentahydroxyflavanone), isolated from a 50% ethanol extract of
      Plantago major seeds (Plantaginaceae), were established to be potent inhibitors
      of the Maillard reaction. These compounds also inhibited the formation of
      advanced glycation end products in proteins in physiological conditions and
      inhibited protein cross-linking glycation. These results indicate that P. major
      seeds have potential therapeutic applications in the prevention of diabetic
      complications. 

PMID- 24895552
TI  - Impact of hemodialysis on dyspnea and lung function in end stage kidney disease
      patients.
AB  - BACKGROUND: Respiratory symptoms are usually underestimated in patients with
      chronic kidney disease undergoing maintenance hemodialysis. Therefore, we set out
      to investigate the prevalence of patients chronic dyspnea and the relationship of
      the symptom to lung function indices. METHODS: Twenty-five clinically stable
      hemodialysis patients were included. The mMRC dyspnea scale was applied before
      and after hemodialysis. Spirometry, single breath nitrogen test, arterial blood
      gases, static maximum inspiratory (P(imax)) and expiratory (P(emax)) muscle
      pressures, and mouth occlusion pressure (P 0.1) were also measured. RESULTS:
      Despite normal spirometry, all patients (100%) reported mild to moderate degree
      of chronic dyspnea pre which was reduced after hemodialysis. The sole predictor
      of (Delta) mMRC was the (Delta) P 0.1 (r = 0.71, P < 0.001). The P(imax) was
      reduced before and correlated with the duration of hemodialysis (r = 0.614, P <
      0.001), whilst after the session it was significantly increased (P < 0.001).
      Finally (Delta) weight was correlated with the (Delta) P(imax) %pred (r = 0.533,
      P = 0,006) and with the (Delta) CV (%pred) (r = 0.65, P < 0.001). CONCLUSION: We
      conclude that dyspnea is the major symptom among the CKD patients that improves
      after hemodialysis. The neuromechanical dissociation observed probably is one of
      the major pathophysiologic mechanisms of dyspnea.

PMID- 24895553
TI  - Independent value of cardiac troponin T and left ventricular global longitudinal
      strain in predicting all-cause mortality among stable hemodialysis patients with
      preserved left ventricular ejection fraction.
AB  - Using a speckle-tracking echocardiography (STE), we recently demonstrated that a
      left ventricular (LV) global longitudinal strain (GLS) >= -15% and the serum
      cardiac troponin T (cTnT) concentration are associated with mortality in stable
      hemodialysis patients with preserved LV ejection fraction (LVEF). In this study,
      we explored the relationship between cTnT and echocardiographic parameters and
      evaluated whether the prognostic value provided by cTnT is independent of a GLS
      >= -15% and vice versa. Eighty-eight stable hemodialysis patients with preserved
      LVEF were followed for 31 months. STE studies and measurements of cTnT were
      performed at baseline. CTnT concentration had a modest correlation with GLS (rs =
      0.44; P < 0.001) but had a weak or nonsignificant correlation with other
      echocardiographic parameters. Adjusting for clinical parameters, hazard ratios
      for each increase of 0.01 ng/mL in cTnT, and a GLS >= -15% on mortality were 1.13
      (P = 0.009) and 3.09 (P = 0.03) without significant interaction between cTnT and
      GLS >= -15%. In addition, an increased cTnT concentration, a GLS >= -15%, or
      their combination showed significant additional predictive value for mortality
      when included in models consisting of clinical parameters. Therefore, both cTnT
      and a GLS >= -15% are independent predictors of mortality and are useful for risk
      stratification.

PMID- 24895554
TI  - Long-term effects of maternal deprivation on the neuronal soma area in the rat
      neocortex.
AB  - Early separation of rat pups from their mothers (separatio a matrem) is
      considered and accepted as an animal model of perinatal stress. Adult rats,
      separated early postnatally from their mothers, are developing long-lasting
      changes in the brain and neuroendocrine system, corresponding to the findings
      observed in schizophrenia and affective disorders. With the aim to investigate
      the morphological changes in this animal model we exposed 9-day-old (P9) Wistar
      rats to a 24 h maternal deprivation (MD). At young adult age rats were sacrificed
      for morphometric analysis and their brains were compared with the control group
      bred under the same conditions, but without MD. Rats exposed to MD had a 28%
      smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial
      cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No
      difference was observed in the expression of glial fibrillary acidic protein in
      the neocortex of MD rats compared to the control group. The results of this study
      demonstrate that stress in early life has a long-term effect on neuronal soma
      size in cingulate and retrosplenial cortex and is potentially interesting as
      these structures play an important role in cognition.

PMID- 24895556
TI  - Neovaginal prolapse in male-to-female transsexuals: an 18-year-long experience.
AB  - Neovaginal prolapse is a rare and distressing complication after male-to-female
      sexual reassignment surgery. We retrospectively analysed the prevalence of
      partial and total neo-vaginal prolapses after sexual reassignment surgery in our
      institute. During the years, two different techniques have been adopted with the
      aim of fixing the neovaginal cylinder. In the first, two absorbable sutures are
      placed at the top of the penoscrotal cylinder and fixed to the Denonvilliers
      fascia. In the second, two additional sutures are added from the
      posterior/midpoint of the flap to the prerectal fascia. We enrolled 282
      consecutive transsexual patients. 65 (23.04%) out of the 282 were treated with
      the first technique and the following 217 (76.96%) with the last technique. In
      the first technique, 1 case (1.53%) of total prolapse and 7 cases (10.76%) of
      partial prolapse were observed, while in the other 217 patients treated with the
      second technique only 9 cases of partial prolapse were observed (4.14%) and no
      cases of total prolapse. All prolapses occurred within 6 months from the
      procedure. In our experience, the use of 4 stitches and a more proximal
      positioning of the sutures to fix the penoscrotal apex with the Denonvilliers
      fascia guarantees a lower risk of prolapse. 

PMID- 24895555
TI  - The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein
      inhibitors, and their roles in bone repair and regeneration.
AB  - Hypoxia-inducible factors (HIFs) are oxygen-dependent transcriptional activators
      that play crucial roles in angiogenesis, erythropoiesis, energy metabolism, and
      cell fate decisions. The group of enzymes that can catalyse the hydroxylation
      reaction of HIF-1 is prolyl hydroxylase domain proteins (PHDs). PHD inhibitors
      (PHIs) activate the HIF pathway by preventing degradation of HIF- alpha via
      inhibiting PHDs. Osteogenesis and angiogenesis are tightly coupled during bone
      repair and regeneration. Numerous studies suggest that HIFs and their target
      gene, vascular endothelial growth factor (VEGF), are critical regulators of
      angiogenic-osteogenic coupling. In this brief perspective, we review current
      studies about the HIF pathway and its role in bone repair and regeneration, as
      well as the cellular and molecular mechanisms involved. Additionally, we briefly
      discuss the therapeutic manipulation of HIFs and VEGF in bone repair and bone
      tumours. This review will expand our knowledge of biology of HIFs, PHDs, PHD
      inhibitors, and bone regeneration, and it may also aid the design of novel
      therapies for accelerating bone repair and regeneration or inhibiting bone
      tumours. 

PMID- 24895557
TI  - The role of hemoclips reinforcement in the ligation-assisted endoscopic
      enucleation for small GISTs in gastric fundus.
AB  - BACKGROUND: Endoscopic ultrasonography- (EUS-) assisted band ligation has been
      proven to be a safe and effective procedure for the treatment of small
      gastrointestinal stromal tumors (GISTs) apart from the relatively high risk of
      the postligation perforation of the gastric fundus. The aim of this study is to
      investigate the efficacy of hemoclip reinforcement in treating small GISTs in the
      gastric fundus. METHOD: During a standard endoscopy, a transparent cap attached
      to the endoscopic tip was placed over the lesion to exert sustained maximal
      aspiration before a rubber band was released. Once a definite ligation was
      confirmed by EUS, the tumor was enucleated. Four to 6 hemoclips were placed on
      the folds around the ligation band to reduce the tension of the ligation site.
      RESULTS: The small GISTs were resected completely in 192 patients. Two cases of
      delayed perforation were found 72 hours after the procedure and successfully
      treated with an ordinary conservative method. CONCLUSION: Hemoclip-reinforced
      endoscopic band ligation with systematic follow-up using EUS appears to be a
      simple and effective technique for the resection of small GISTs in the gastric
      fundus.

PMID- 24895558
TI  - The inhibitory effect of somatostatin receptor activation on bee venom-evoked
      nociceptive behavior and pCREB expression in rats.
AB  - The present study examined nociceptive behaviors and the expression of
      phosphorylated cAMP response element-binding protein (pCREB) in the dorsal horn
      of the lumbar spinal cord and the dorsal root ganglion (DRG) evoked by bee venom
      (BV). The effect of intraplantar preapplication of the somatostatin analog
      octreotide on nociceptive behaviors and pCREB expression was also examined.
      Subcutaneous injection of BV into the rat unilateral hindpaw pad induced
      significant spontaneous nociceptive behaviors, primary mechanical allodynia,
      primary thermal hyperalgesia, and mirror-thermal hyperalgesia, as well as an
      increase in pCREB expression in the lumbar spinal dorsal horn and DRG. Octreotide
      pretreatment significantly attenuated the BV-induced lifting/licking response and
      mechanical allodynia. Local injection of octreotide also significantly reduced
      pCREB expression in the lumbar spinal dorsal horn and DRG. Furthermore,
      pretreatment with cyclosomatostatin, a somatostatin receptor antagonist, reversed
      the octreotide-induced inhibition of the lifting/licking response, mechanical
      allodynia, and the expression of pCREB. These results suggest that BV can induce
      nociceptive responses and somatostatin receptors are involved in mediating the
      antinociception, which provides new evidence for peripheral analgesic action of
      somatostatin in an inflammatory pain state. 

PMID- 24895559
TI  - Association between oxidative stress and outcome in different subtypes of acute
      ischemic stroke.
AB  - OBJECTIVES: This study investigated serum thiobarbituric acid-reactive substances
      (TBARS) and free thiol levels in different subtypes of acute ischemic stroke
      (AIS) and evaluated their association with clinical outcomes. METHODS: This
      prospective study evaluated 100 AIS patients, including 75 with small-vessel and
      25 with large-vessel diseases. Serum oxidative stress (TBARS) and antioxidant
      (thiol) were determined within 48 hours and days 7 and 30 after stroke. For
      comparison, 80 age- and sex-matched participants were evaluated as controls.
      RESULTS: Serum TBARS was significantly higher and free thiol was lower in stroke
      patients than in the controls on days 1 and 7 after AIS. The level of free thiol
      was significantly lower in the large-vessel disease than in the small-vessel
      disease on day 7 after stroke. Using the stepwise logistic regression model for
      potential variables, only stroke subtype, NIHSS score, and serum TBARS level were
      independently associated with three-month outcome. Higher TBARS and lower thiol
      levels in the acute phase of stroke were associated with poor outcome.
      CONCLUSIONS: Patients with large-vessel disease have higher oxidative stress but
      lower antioxidant defense compared to those with small-vessel disease after AIS.
      Serum TBARS level at the acute phase of stroke is a potential predictor for three
      month outcome.

PMID- 24895560
TI  - Newborn first feed and prelacteal feeds in Mansoura, Egypt.
AB  - BACKGROUND: Prelacteal feed (feeding any other substance before first
      breastfeeding) appears to be common despite its harmful effects. By definition a
      child provided with prelacteal feed (PLF) is not exclusively breastfed and PLF
      has many implications for the success and early initiation of breastfeeding.
      Objectives. To describe the prevalence of, nature of, and reasons for and factors
      associated with PLF. METHODS: 647 mother-infant dyads were studied. Data was
      collected about the sociodemographic features of the family and baby, maternity
      care, the type of first feed before suckling, and causes of PLF. Maternal weight
      and height were measured and body mass index was calculated. RESULTS: About 58%
      of newborns received prelacteal feeds. The commonest PLF was sugar/glucose water
      (39.6%). The most frequent reasons for giving PLF are tradition (61.0%) and
      mother's/mother in law's advice (58.3%). The logistic regression revealed that
      the independent predictors of PLF are urban residence; maternal education;
      father's education; low, middle, and high social class; maternal obesity;
      receiving antenatal care at private clinics and no antenatal care; Caesarean
      section; female babies; low birth weight; and admission to neonatal intensive
      care. CONCLUSION: Indiscriminate use of PLF should be discouraged in medical
      education and in antenatal maternal health education.

PMID- 24895561
TI  - A few good reasons why species-area relationships do not work for parasites.
AB  - Several studies failed to find strong relationships between the biological and
      ecological features of a host and the number of parasite species it harbours. In
      particular, host body size and geographical range are generally only weak
      predictors of parasite species richness, especially when host phylogeny and
      sampling effort are taken into account. These results, however, have been
      recently challenged by a meta-analytic study that suggested a prominent role of
      host body size and range extent in determining parasite species richness (species
      area relationships). Here we argue that, in general, results from meta-analyses
      should not discourage researchers from investigating the reasons for the lack of
      clear patterns, thus proposing a few tentative explanations to the fact that
      species-area relationships are infrequent or at least difficult to be detected in
      most host-parasite systems. The peculiar structure of host-parasite networks, the
      enemy release hypothesis, the possible discrepancy between host and parasite
      ranges, and the evolutionary tendency of parasites towards specialization may
      explain why the observed patterns often do not fit those predicted by species
      area relationships. 

PMID- 24895562
TI  - Visual and anatomical outcomes of intravitreal aflibercept for treatment
      resistant neovascular age-related macular degeneration.
AB  - A retrospective chart review of patients with persistent subretinal and/or
      intraretinal fluid, despite previous treatment with intravitreal ranibizumab (0.5
      mg), who were switched to aflibercept injections, was performed. Treatment was
      three monthly aflibercept (2 mg) injections followed by dosing on pro re nata
      basis. Main outcome measures included changes in best corrected visual acuity
      (BCVA), 1 mm central subfield (CSF) retinal thickness, the height of the pigment
      epithelial detachment (PED), and subfoveal choroidal thickness on optical
      coherence tomography at 6 months. Thirty-one eyes of 30 patients were analyzed.
      The mean number of injections before aflibercept conversion was 34.4 +/- 11.9.
      After an average of 4.5 aflibercept injections (range 3 to 6) over 6 months, no
      significant change in BCVA was observed (P > 0.05). Compared with baseline, there
      was a significant reduction of the CSF retinal thickness (449 +/- 179 versus 269
      +/- 145  MU m, P < 0.001), maximum PED height (262 +/- 134 versus 183 +/- 100  MU
      m, P < 0.001), and choroidal thickness (192 +/- 67 versus 167 +/- 51  MU m, P <
      0.01). Stable visual acuity and anatomical improvement were obtained for up to 6
      months after aflibercept conversion. However, choroidal thinning related to
      treatment was observed. 

PMID- 24895563
TI  - Grain sterility in relation to dry mass production and distribution in rice
      (Oryza sativa L.).
AB  - The experiment was conducted to investigate potential causes of grain sterility
      in widely cultivated rice variety in Malaysia, MR219 and its two mutant lines
      (RM311 and RM109) by examining the source-sink relations. RM311 produced
      increased dry matter yield both at heading and maturity and also showed higher
      grain yield with greater proportion of grain sterility than the other two
      genotypes (RM109 and MR219) resulting in the lowest harvest index (49.68%). In
      contrast, harvest index was greater in RM109 (53.34%) and MR219 (52.76%) with
      less grain sterility percentage than MR311 indicating that dry matter
      partitioning to economic yield was better in RM109 and MR219 than in MR311.
      Results indicated that dry matter allocation per spikelet from heading to
      maturity was important for reducing grain sterility in rice. The greater above
      ground crop dry matter per spikelet was observed in RM109 and MR219 as compared
      to high dry matter producing genotype; RM311 implies that poor grain filling may
      not have resulted from dry matter production or source limitation. These findings
      suggest that grain sterility or poor grain filling in rice is the result of poor
      translocation and partitioning of assimilates into grains (sink) rather than of
      limited biomass production or source limitation. 

PMID- 24895564
TI  - Immobilization of a Pleurotus ostreatus laccase mixture on perlite and its
      application to dye decolourisation.
AB  - In the present study, a crude laccase preparation from Pleurotus ostreatus was
      successfully immobilized on perlite, a cheap porous silica material, and tested
      for Remazol Brilliant Blue R (RBBR) decolourisation in a fluidized bed recycle
      reactor. Results showed that RBBR decolourisation is mainly due to enzyme action
      despite the occurrence of dye adsorption-related enzyme inhibition. Fine tuning
      of immobilization conditions allowed balancing the immobilization yield and the
      resulting rate of decolourisation, with the adsorption capacity of the solid
      biocatalyst. In the continuous lab scale reactor, a maximum conversion degree of
      56.1% was achieved at reactor space-time of 4.2 h. Stability and catalytic
      parameters of the immobilized laccases were also assessed in comparison with the
      soluble counterparts, revealing an increase in stability, despite a reduction of
      the catalytic performances. Both effects are most likely ascribable to the
      occurrence of multipoint attachment phenomena. 

PMID- 24895566
TI  - The effect of prior upper body exercise on subsequent wingate performance.
AB  - It has been reported previously that the upper body musculature is continually
      active during high intensity cycle ergometry. The aim of this study was to
      examine the effects of prior upper body exercise on subsequent Wingate (WAnT)
      performance. Eleven recreationally active males (20.8 +/- 2.2 yrs; 77.7 +/- 12.0
      kg; 1.79 +/- 0.04 m) completed two trials in a randomised order. In one trial
      participants completed 2 * 30 s WAnT tests (WAnT1 and WAnT2) with a 6 min
      recovery period; in the other trial, this protocol was preceded with 4 sets of
      biceps curls to induce localised arm fatigue. Prior upper body exercise was found
      to have a statistically significant detrimental effect on peak power output (PPO)
      during WAnT1 (P < 0.05) but no effect was observed for mean power output (MPO) (P
      > 0.05). Handgrip (HG) strength was also found to be significantly lower
      following the upper body exercise. These results demonstrate that the upper body
      is meaningfully involved in the generation of leg power during intense cycling. 

PMID- 24895565
TI  - Synthesis and antimicrobial activities of 5-Arylidene-thiazolidine-2,4-dione
      derivatives.
AB  - Antibiotic resistance is considered one of the world's major public health
      concerns. The main cause of bacterial resistance is the improper and repeated use
      of antibiotics. To alleviate this problem, new chemical substances against
      microorganisms are being synthesized and tested. Thiazolidines are compounds
      having many pharmacological activities including antimicrobial activities. For
      this purpose some thiazolidine derivatives substituted at position 5 in the
      thiazolidine nucleus were synthesized and tested against several microorganisms.
      Using a disc diffusion method, antimicrobial activity was verified against Gram
      positive, Gram-negative, and alcohol acid resistant bacteria and yeast. The
      minimum inhibition concentrations (MIC) and minimum bactericidal concentrations
      (MBC) were determined. All derivatives showed antimicrobial activity mainly
      against Gram-positive bacteria, with MIC values ranging from 2 to 16 ug/mL. 

PMID- 24895567
TI  - Management of anterior skull base defect depending on its size and location.
AB  - INTRODUCTION: We present our experience in the reconstruction of these leaks
      depending on their size and location. MATERIAL AND METHODS: Fifty-four patients
      who underwent advanced skull base surgery (large defects, >20 mm) and 62 patients
      with CSF leaks of different origin (small, 2-10 mm, and midsize, 11-20 mm,
      defects) were included in the retrospective study. Large defects were
      reconstructed with a nasoseptal pedicled flap positioned on fat and fascia lata.
      In small and midsized leaks. Fascia lata in an underlay position was used for its
      reconstruction covered with mucoperiosteum of either the middle or the inferior
      turbinate. RESULTS: The most frequent etiology for small and midsized defects was
      spontaneous (48.4%), followed by trauma (24.2%), iatrogenic (5%). The success
      rate after the first surgical reconstruction was 91% and 98% in large skull base
      defects and small/midsized, respectively. Rescue surgery achieved 100%.
      CONCLUSIONS: Endoscopic surgery for any type of skull base defect is the gold
      standard. The size of the defects does not seem to play a significant role in the
      success rate. Fascia lata and mucoperiosteum of the turbinate allow a two-layer
      reconstruction of small and midsized defects. For larger skull base defects, a
      combination of fat, fascia lata, and nasoseptal pedicled flaps provides a
      successful reconstruction.

PMID- 24895568
TI  - Association between the delta estimated glomerular filtration rate and the
      prevalence of monoclonal gammopathy of undetermined significance in Korean males.
AB  - BACKGROUND: We investigated the association between the reduction in the
      estimated glomerular filtration rate (eGFR) and the prevalence of monoclonal
      gammopathy of undetermined significance (MGUS) in Korean males. METHODS: We
      enrolled 723 healthy Korean males. Serum creatinine concentration, serum
      electrophoresis, serum immunofixation, and the serum free light chain assay were
      performed. We calculated delta eGFR per year (DeltaeGFR/yr). The prevalence of
      MGUS was compared based on the DeltaeGFR/yr and age group. RESULTS: Thirteen
      (1.8%) of 723 participants exhibited the monoclonal band on serum immunofixation.
      Prevalence of MGUS by age group was 0.00% (0/172 for 40 years), 1.63% (6/367 for
      60 years), and 3.80% (7/184 for >60 years). The median decrease in DeltaeGFR/yr
      was 5.3%. The prevalence of MGUS in participants in their 50s with >5.3% decline
      in DeltaeGFR/yr was significantly higher than those with <5.3% decrease in
      DeltaeGFR/yr (3.16% versus 0.00%; P = 0.049). The prevalence of MGUS in
      participants in their 50s with >5.3% decrease in DeltaeGFR/yr was similar to that
      of healthy males in their 60s. CONCLUSION: Using the rate of reduction in
      DeltaeGFR/yr in healthy Korean males who had their serum creatinine level checked
      regularly may increase the MGUS detection rate in clinical practice.

PMID- 24895569
TI  - Bacterial sepsis in patients with visceral leishmaniasis in Northwest Ethiopia.
AB  - BACKGROUND AND OBJECTIVES: Visceral leishmaniasis (VL) is one of the neglected
      diseases affecting the poorest segment of world populations. Sepsis is one of the
      predictors for death of patients with VL. This study aimed to assess the
      prevalence and factors associated with bacterial sepsis, causative agents, and
      their antimicrobial susceptibility patterns among patients with VL. METHODS: A
      cross-sectional study was conducted among parasitologically confirmed VL patients
      suspected of sepsis admitted to the University of Gondar Hospital, Northwest
      Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical
      samples were collected and cultured following the standard procedures. RESULTS:
      Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial
      sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%;
      11/16), including two methicillin-resistant isolates (MRSA). Patients with focal
      bacterial infection were more likely to have bacterial sepsis (P < 0.001).
      CONCLUSIONS: The prevalence of culture confirmed bacterial sepsis was high,
      predominantly due to S. aureus. Concurrent focal bacterial infection was
      associated with bacterial sepsis, suggesting that focal infections could serve as
      sources for bacterial sepsis among VL patients. Careful clinical evaluation for
      focal infections and prompt initiation of empiric antibiotic treatment appears
      warranted in VL patients.

PMID- 24895570
TI  - MYD88 L265P mutations are correlated with 6q deletion in Korean patients with
      Waldenstrom macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is a malignant lymphoplasma-proliferative
      disorder with IgM monoclonal gammopathy. A recent whole-genome study identified
      MYD88 L265P as the key mutation in WM. We investigated MYD88 mutations in
      conjunction with cytogenetic study in 22 consecutive Korean WM patients.
      Conventional G-banding and interphase fluorescence in situ hybridization (FISH)
      were performed at regions including 6q21 using bone marrow (BM) aspirates.
      Sixteen patients were subjected to Sanger sequencing-based MYD88 mutation study.
      Five patients (28%) showed cytogenetic aberrations in G-banding. The incidence of
      6q21 deletion was 17% by conventional G-banding and 37% by FISH. Ten patients
      (45%) showed cytogenetic aberrations using FISH: 6q deletion in eight (37%) and
      IGH rearrangement in four (18%). Two patients had both the 6q deletion and IGH
      rearrangement, and two had only the IGH rearrangement. Eleven patients (69%)
      presented with the MYD88 L265P mutation. MYD88 mutations were significantly
      associated with the presence of 6q deletions (P = 0.037). Six patients with the
      6q deletion for whom sequencing was possible were found to harbor MYD88
      mutations. The MYD88 L265P mutation was also associated with increased lymphocyte
      burden in BM biopsy. This is the first report of high frequency MYD88 L265P
      mutations in Korean WM patients. 

PMID- 24895571
TI  - Preparation of North American type II PRRSV infectious clone expressing green
      fluorescent protein.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is still one of the
      most important infectious diseases threatening the swine industry. To construct
      North American type II PRRSV infectious clone containing green fluorescent
      protein (GFP) gene, we amplify gfp gene, flanked by PRRSV Nsp2 gene fragments
      upstream and downstream, using overlap PCR method from pcDNA-EF1-GFP plasmid and
      FL12 plasmid containing PRRSV infectious genome as the templates. The Nsp2
      fragment-flanked gfp gene was inserted into Nsp2 gene of the FL12 plasmid by Spe
      I and Xho I sites to generate PRRSV infectious recombinant plasmid (FL12-GFP)
      containing gfp gene. The recombinant PRRSV expressing GFP (PRRSV-GFP) was rescued
      in baby hamster kidney-21 (BHK-21) cells by transfecting PRRSV mRNA synthesized
      in vitro and amplified in Marc-145 cells. The PRRSV-GFP infectivity and
      replication capacity were identified. Results showed that, by adopting overlap
      PCR strategy, the gfp gene was successfully inserted into and fused with PRRSV
      Nsp2 gene in the PRRSV infectious clone plasmid FL-12 to generate FL12-GFP
      plasmid. The recombinant PRRSV-GFP was generated through transfecting PRRSV mRNA
      in BHK-2 cells. Like its parental virus, the recombinant PRRSV-GFP maintains its
      infectivity to Marc-145 cells and porcine alveolar macrophages (PAMs). This study
      provides essential conditions for further investigation on PRRSV. 

PMID- 24895572
TI  - Functional interactions between 17 beta -estradiol and progesterone regulate
      autophagy during acini formation by bovine mammary epithelial cells in 3D
      cultures.
AB  - Mammary gland epithelium forms a network of ducts and alveolar units under
      control of ovarian hormones: 17-beta-estradiol (E2) and progesterone (P4).
      Mammary epithelial cells (MECs) cultured on reconstituted basement membrane (rBM)
      form three-dimensional (3D) acini composed of polarized monolayers surrounding a
      lumen. Using the 3D culture of BME-UV1 bovine MECs we previously demonstrated
      that autophagy was induced in the centrally located cells of developing
      spheroids, and sex steroids increased this process. In the present study we
      showed that E2 and P4 enhanced the expression of ATG3, ATG5, and BECN1 genes
      during acini formation, and this effect was accelerated in the presence of both
      hormones together. The stimulatory action of E2 and P4 was also reflected by
      increased levels of Atg5, Atg3, and LC3-II proteins. Additionally, the activity
      of kinases involved in autophagy regulation, Akt, ERK, AMPK, and mTOR, was
      examined. E2 + P4 slightly increased the level of phosphorylated AMPK but
      diminished phosphorylated Akt and mTOR on day 9 of 3D culture. Thus, the
      synergistic actions of E2 and P4 accelerate the development of bovine mammary
      acini, which may be connected with stimulation of ATGs expression, as well as
      regulation of signaling pathways (PI3K/Akt/mTOR; AMPK/mTOR) involved in autophagy
      induction.

PMID- 24895573
TI  - Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma
      cells.
AB  - Previously, we found that the expression of microRNA-146a (miR-146a) was
      downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded
      (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the
      current study, we have explored the in vitro effect of miR-146a on the malignant
      phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase
      cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by
      spectrophotometry, fluorimetry, and fluorescence microscopy, respectively.
      Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2,
      and stat5 signalings. These effects were less potent compared to that of a siRNA
      targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could
      enhance the cell growth inhibition and apoptosis induction impact of various EGFR
      targeting agents. The most potent combination was miR-146a mimic with cetuximab,
      presenting a synergistic effect. In conclusion, miR-146a plays a vital role in
      the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a
      critical targeted molecular therapy strategy for HCC. 

PMID- 24895574
TI  - Cytotoxic effect of icaritin and its mechanisms in inducing apoptosis in human
      burkitt lymphoma cell line.
AB  - Icaritin (ICT), a hydrolytic product of icariin from Epimedium genus, exhibits
      antitumor activities in several human solid-tumor and myeloid leukemia cells with
      extensive influence on various cell signal molecules, such as MAPKs being
      involved in cell proliferation and Bcl-2 participating in cell apoptosis.
      However, the effect of icaritin on Burkitt Lymphoma has not been elucidated. In
      the present study, we first screened the potential effect of icaritin on Burkitt
      lymphoma Raji and P3HR-1 cell lines and found that icaritin showed cytotoxicity
      in both cell lines. We further found that icaritin could significantly inhibit
      Raji cells proliferation with S-phase arrest of cell cycle and induced cell
      apoptosis accompanied by activation of caspase-8 and caspase-9 and cleavage of
      PARP. We also observed that icaritin was able to decrease Bcl-2 levels, thus
      shifting the Bcl-2/Bax ratio, and it could obviously reduce c-Myc, a specific
      molecular target in Burkitt lymphoma. Our findings demonstrated that icaritin
      showed cytotoxicity, inhibited cell growth, caused S arrest, and induced
      apoptosis in Burkitt lymphoma cells and provided a rationale for the further
      evaluation of icaritin for Burkitt lymphoma therapy. 

PMID- 24895576
TI  - Platelet function tests: a review of progresses in clinical application.
AB  - The major goal of traditional platelet function tests has been to screen and
      diagnose patients who present with bleeding problems. However, as the central
      role of platelets implicated in the etiology of arterial thrombotic diseases such
      as myocardial infarction and stroke became widely known, platelet function tests
      are now being promoted to monitor the efficacy of antiplatelet drugs and also to
      potentially identify patients at increased risk of thrombosis. Beyond hemostasis
      and thrombosis, an increasing number of studies indicate that platelets play an
      integral role in intercellular communication, are mediators of inflammation, and
      have immunomodulatory activity. As new potential biomarkers and technologies
      arrive at the horizon, platelet functions testing appears to take on a new
      aspect. This review article discusses currently available clinical application of
      platelet function tests, placing emphasis on essential characteristics. 

PMID- 24895575
TI  - Expression of stem cell and epithelial-mesenchymal transition markers in
      circulating tumor cells of breast cancer patients.
AB  - Evaluation and characterization of circulating tumor cells (CTCs) have become a
      major focus of translational cancer research. Presence of CTCs predicts worse
      clinical outcome in early and metastatic breast cancer. Whether all cells from
      the primary tumor have potential to disseminate and form subsequent metastasis
      remains unclear. As part of the metastatic cascade, tumor cells lose their cell
      to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to
      enter blood circulation. During EMT epithelial antigens are downregulated; thus,
      such tumor cells might elude classical epithelial marker-based detection. Several
      researchers postulated that some CTCs express stem cell-like phenotype; this
      might lead to chemoresistance and enhanced metastatic potential of such cells. In
      the present review, we discuss current data on EMT and stem cell markers in CTCs
      of breast cancer and their clinical significance. 

PMID- 24895577
TI  - Biomaterials in cardiovascular research: applications and clinical implications.
AB  - Cardiovascular biomaterials (CB) dominate the category of biomaterials based on
      the demand and investments in this field. This review article classifies the CB
      into three major classes, namely, metals, polymers, and biological materials and
      collates the information about the CB. Blood compatibility is one of the major
      criteria which limit the use of biomaterials for cardiovascular application.
      Several key players are associated with blood compatibility and they are
      discussed in this paper. To enhance the compatibility of the CB, several surface
      modification strategies were in use currently. Some recent applications of
      surface modification technology on the materials for cardiovascular devices were
      also discussed for better understanding. Finally, the current trend of the CB,
      endothelization of the cardiac implants and utilization of induced human
      pluripotent stem cells (ihPSCs), is also presented in this review. The field of
      CB is growing constantly and many new investigators and researchers are
      developing interest in this domain. This review will serve as a one stop
      arrangement to quickly grasp the basic research in the field of CB. 

PMID- 24895578
TI  - Emetic Bacillus cereus are more volatile than thought: recent foodborne outbreaks
      and prevalence studies in Bavaria (2007-2013).
AB  - Several Bacillus cereus strains possess the genetic fittings to produce two
      different types of toxins, the heat-stable cereulide or different heat-labile
      proteins with enterotoxigenic potential. Unlike the diarrheal toxins, cereulide
      is (pre-)formed in food and can cause foodborne intoxications shortly after
      ingestion of contaminated food. Based on the widely self-limiting character of
      cereulide intoxications and rarely performed differential diagnostic in routine
      laboratories, the real incidence is largely unknown. Therefore, during a 7-year
      period about 4.300 food samples linked to foodborne illness with a preliminary
      report of vomiting as well as food analysed in the context of monitoring programs
      were investigated to determine the prevalence of emetic B. cereus in food
      environments. In addition, a lux-based real-time monitoring system was employed
      to assess the significance of the detection of emetic strains in different food
      matrices and to determine the actual risk of cereulide toxin production in
      different types of food. This comprehensive study showed that emetic strains are
      much more volatile than previously thought. Our survey highlights the importance
      and need of novel strategies to move from the currently taxonomic-driven
      diagnostic to more risk orientated diagnostics to improve food and consumer
      safety. 

PMID- 24895579
TI  - The putative HORMA domain protein Atg101 dimerizes and is required for starvation
      induced and selective autophagy in Drosophila.
AB  - The large-scale turnover of intracellular material including organelles is
      achieved by autophagy-mediated degradation in lysosomes. Initiation of autophagy
      is controlled by a protein kinase complex consisting of an Atg1-family kinase,
      Atg13, FIP200/Atg17, and the metazoan-specific subunit Atg101. Here we show that
      loss of Atg101 impairs both starvation-induced and basal autophagy in Drosophila.
      This leads to accumulation of protein aggregates containing the selective
      autophagy cargo ref(2)P/p62. Mapping experiments suggest that Atg101 binds to the
      N-terminal HORMA domain of Atg13 and may also interact with two unstructured
      regions of Atg1. Another HORMA domain-containing protein, Mad2, forms a
      conformational homodimer. We show that Drosophila Atg101 also dimerizes, and it
      is predicted to fold into a HORMA domain. Atg101 interacts with ref(2)P as well,
      similar to Atg13, Atg8a, Atg16, Atg18, Keap1, and RagC, a known regulator of Tor
      kinase which coordinates cell growth and autophagy. These results raise the
      possibility that the interactions and dimerization of the putative HORMA domain
      protein Atg101 play critical roles in starvation-induced autophagy and
      proteostasis, by promoting the formation of protein aggregate-containing
      autophagosomes. 

PMID- 24895580
TI  - Mutation analysis of JAK2V617F, FLT3-ITD, NPM1, and DNMT3A in Chinese patients
      with myeloproliferative neoplasms.
AB  - Since the discovery of JAK2V617F tyrosine kinase-activating mutation, several
      genes have been found mutated in myeloproliferative neoplasms (MPNs). FLT3-ITD,
      NPM1, and DNMT3A mutations frequently occurred in AML patients and have been
      found conferred with myeloproliferative neoplasms in mouse model. Therefore, we
      sought to search for mutations in JAK2V617F, FLT3-ITD, NPM1, and DNMT3A in 129
      cases including 120 classic MPN cases and 9 MDS/MPN cases. JAK2V617F mutation was
      found in 60% of the 120 classic MPNs. However, none of the patients displayed
      FLT3-ITD and NPM1 mutations; only 2 patients harbored DNMT3A R882 mutation.
      Further studies including whole-genome sequence will be conducted to investigate
      the possible involvement of these genes in MPN. 

PMID- 24895581
TI  - Characterization of the Opp peptide transporter of Corynebacterium
      pseudotuberculosis and its role in virulence and pathogenicity.
AB  - Despite the economic importance of caseous lymphadenitis (CLA), a chronic disease
      caused by Corynebacterium pseudotuberculosis, few genes related to the virulence
      of its etiologic agent have been characterized. The oligopeptide permease (Opp)
      transporters are located in the plasma membrane and have functions generally
      related to the uptake of peptides from the extracellular environment. These
      peptide transporters, in addition to having an important role in cell nutrition,
      also participate in the regulation of various processes involving intercellular
      signaling, including the control of the expression of virulence genes in
      pathogenic bacteria. To study the role of Opp in C. pseudotuberculosis, an OppD
      deficient strain was constructed via simple crossover with a nonreplicative
      plasmid carrying part of the oppD gene sequence. As occurred to the wild-type,
      the DeltaoppD strain showed impaired growth when exposed to the toxic glutathione
      peptide (GSH), indicating two possible scenarios: (i) that this component can be
      internalized by the bacterium through an Opp-independent pathway or (ii) that
      there is toxicity while the peptide is extracellular. Additionally, the DeltaoppD
      mutant presented a reduced ability to adhere to and infect macrophages compared
      to the wild-type, although both strains exhibit the same potential to colonize
      spleens and cause injury and death to infected mice. 

PMID- 24895582
TI  - Human Schwann cells seeded on a novel collagen-based microstructured nerve guide
      survive, proliferate, and modify neurite outgrowth.
AB  - A variety of new bioartificial nerve guides have been tested preclinically for
      their safety and nerve regeneration supporting properties. So far, only a limited
      number of biomaterials have been tested in humans since the step from preclinical
      work to a clinical application is challenging. We here present an in vitro model
      with human Schwann cells (hSCs) as an intermediate step towards clinical
      application of the nerve guide Perimaix, a collagen-based microstructured 3D
      scaffold containing numerous longitudinal guidance channels for directed axonal
      growth. hSCs were seeded onto different prototypes of Perimaix and cultivated for
      14 days. hSC adhered to the scaffold, proliferated, and demonstrated healthy
      Schwann cell morphology (spindle shaped cell bodies, bipolar oriented processes)
      not only at the surface of the material, but also in the deeper layers of the
      scaffold. The general well-being of the cells was quantitatively confirmed by low
      levels of lactate dehydrogenase release into the culture medium. Moreover,
      conditioned medium of hSCs that were cultivated on Perimaix was able to modify
      neurite outgrowth from sensory dorsal root ganglion neurons. Overall these data
      indicate that Perimaix is able to provide a matrix that can promote the
      attachment and supports process extension, migration, and proliferation of hSC. 

PMID- 24895583
TI  - In vitro antibacterial, antioxidant, and cytotoxic activities of Parthenium
      hysterophorus and characterization of extracts by LC-MS analysis.
AB  - Present work reports the biological activities of P. hysterophorus leaf, stem,
      flower, and root. Dried samples were sequentially extracted with many solvents.
      Hexane (HX), benzene (BZ), and chloroform (CH) extracts of leaf showed
      considerable antibacterial activity against Streptococcus mutans (MTCC 497),
      Proteus vulgaris (MTCC 7299), and Salmonella typhi (MTCC 3917). Flower extracts
      exhibited presence of higher amount of flavonoids (13.9-59.6 MUgQE/mg) followed
      by leaf, stem, and root. Stem (HX, BZ, and CH), leaf ethanol (ET), and root (HX,
      BZ, and CH) fractions showed noticeable antioxidant capacity in phosphomolybdate
      assay. Most of the extracts demonstrated beta carotene bleaching inhibition
      capability. BZ, ethyl acetate (EA), and ET fractions of leaves, stem aqueous
      (AQ), and flower EA extracts showed membrane protective activities (40-55%).
      Middle fractions of the plant parts displayed moderate antihemolytic potential.
      Most of the flower extracts exhibited cytotoxic activity (80-100%) against lung
      and colon cancer cell lines. Root (HX and ET) and leaf ET extracts showed
      considerable inhibition (90-99%) of colon and ovary cancer cell lines. The LC-MS
      scan demonstrated presence of different compounds showing 3-20 min retention
      time. The study revealed considerable antibacterial, antioxidant, lipo
      protective, antihemolytic, and anticancer potential in all parts of P.
      hysterophorus.

PMID- 24895584
TI  - Endodontic and clinical considerations in the management of variable anatomy in
      mandibular premolars: a literature review.
AB  - Mandibular premolars are known to have numerous anatomic variations of their
      roots and root canals, which are a challenge to treat endodontically. The paper
      reviews literature to detail the various clinically relevant anatomic
      considerations with detailed techniques and methods to successfully manage these
      anomalies. An emphasis and detailed description of every step of treatment
      including preoperative diagnosis, intraoperative identification and management,
      and surgical endodontic considerations for the successful management of these
      complex cases have been included. 

PMID- 24895585
TI  - BAG3 and HIF-1 alpha coexpression detected by immunohistochemistry correlated
      with prognosis in hepatocellular carcinoma after liver transplantation.
AB  - OBJECTIVE: The objective is to determine the effects of BAG3 and HIF-1 alpha
      expression on the prognosis of HCC patients after liver transplantation. METHODS:
      Samples from 31 patients with HCC receiving liver transplantation were collected
      for this study. The immunohistochemistry was used to detect the expression of
      BAG3 and HIF-1 alpha of HCC samples. RESULTS: According to the
      immunohistochemistry results, BAG3 and HIF-1 alpha staining were significantly
      associated with tumor TNM stage (P = 0.004, P = 0.012). A significant association
      between high BAG3/HIF-1 alpha levels and a shorter overall survival was detected,
      so as the combined BAG3 and HIF-1 alpha analysis. CONCLUSION: The results
      suggested that the expression level of BAG3 and HIF-1 alpha is efficient
      prognostic parameters in patients with HCC after liver transplantation.

PMID- 24895586
TI  - Human cytomegalovirus-encoded miR-US25-1 aggravates the oxidised low density
      lipoprotein-induced apoptosis of endothelial cells.
AB  - Human cytomegalovirus (HCMV) infection is linked to the development and severity
      of the cardiovascular disease atherosclerosis; however, there is little known
      about the promotion of atherosclerosis. miR-US25-1 is one of HCMV-encoded miRNAs
      and targets cellular genes that are essential for virus growth to control the
      life cycle of the virus and host cells. The prominent regulation on cell cycle
      genes of the miR-US25-1 attracts us to explore its role in the atherosclerosis
      promotion. It was indicated that miR-US25-1 level was upregulated in subjects or
      in endothelial cells with HCMV infection; and the miR-US25-1 downregulated the
      expression of BRCC 3 by targeting the 5' UTR of BRCC 3. And a miR-US25-1 mimics
      transfection could reduce the EAhy926 cell viability but did not induce apoptosis
      in EAhy926 cells. And what is more, miR-US25-1 mimicis transfection deteriorated
      the ox-LDL-induced apoptosis and aggravated the upregulation of apoptosis
      associated molecules by oxidised low density lipoprotein (ox-LDL) in EAhy926
      cells. And we have also confirmed the deregulation of BRCC 3 expression by miR
      US25-1 by targeting the 5' UTR of it. Given the vital role of BRCC 3 in DNA
      damage repairing, we speculated that the targeting inhibition of BRCC 3 by miR
      US25-1 may contribute to the aggravation of ox-LDL-promoted apoptosis of
      endothelial EAhy926 cells.

PMID- 24895587
TI  - Network of microRNAs-mRNAs interactions in pancreatic cancer.
AB  - BACKGROUND: MicroRNAs are small RNA molecules that regulate the expression of
      certain genes through interaction with mRNA targets and are mainly involved in
      human cancer. This study was conducted to make the network of miRNAs-mRNAs
      interactions in pancreatic cancer as the fourth leading cause of cancer death.
      METHODS: 56 miRNAs that were exclusively expressed and 1176 genes that were
      downregulated or silenced in pancreas cancer were extracted from beforehand
      investigations. MiRNA-mRNA interactions data analysis and related networks were
      explored using MAGIA tool and Cytoscape 3 software. Functional annotations of
      candidate genes in pancreatic cancer were identified by DAVID annotation tool.
      RESULTS: This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241
      edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR
      24 was the most significantly powerful miRNA that regulated series of important
      genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that
      downregulated. CONCLUSION: Although the collected previous data seems to be a
      treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs
      interaction. Network of miRNA-mRNA interactions will help to corroborate
      experimental remarks and could be used to refine miRNA target predictions for
      developing new therapeutic approaches.

PMID- 24895590
TI  - Retraction. Stable plastid transformation for high-level recombinant protein
      expression: promises and challenges.

PMID- 24895588
TI  - The ineffective role of cathodal tDCS in enhancing the functional motor outcomes
      in early phase of stroke rehabilitation: an experimental trial.
AB  - Transcranial direct current stimulation (tDCS) is a noninvasive technique that
      could improve the rehabilitation outcomes in stroke, eliciting neuroplastic
      mechanisms. At the same time conflicting results have been reported in subacute
      phase of stroke, when neuroplasticity is crucial. The aim of this double-blind,
      randomized, and sham-controlled study was to determine whether a treatment with
      cathodal tDCS before the rehabilitative training might augment the final outcomes
      (upper limb function, hand dexterity and manual force, locomotion, and activities
      of daily living) in respect of a traditional rehabilitation for a sample of
      patients affected by ischemic stroke in the subacute phase. An experimental group
      (cathodal tDCS plus rehabilitation) and a control group (sham tDCS plus
      rehabilitation) were assessed at the beginning of the protocol, after 10 days of
      stimulation, after 30 days from ending of stimulation, and at the end of
      inpatient rehabilitation. Both groups showed significant improvements for all the
      assessed domains during the rehabilitation, except for the manual force, while no
      significant differences were demonstrated between groups. These results seem to
      indicate that the cathodal tDCS, provided in an early phase of stroke, does not
      lead to a functional improvement. To depict a more comprehensive scenario,
      further studies are needed. 

PMID- 24895589
TI  - Synergistic effect and antiquorum sensing activity of Nymphaea tetragona (water
      lily) extract.
AB  - Salmonellosis is a common and widely distributed food borne disease where
      Salmonella typhimurium is one of the most important etiologic agents. The purpose
      of this study was to investigate the antimicrobial activity of Nymphaea tetragona
      alone and in combination with antibiotics against S. typhimurium. It also aimed
      to assess the plant for quorum sensing inhibition (QSI) activity and to identify
      the bioactive compounds. The antibacterial activities of the extract were
      assessed using broth microdilution method. Disk agar diffusion method was
      employed to determine the QSI and bioactive compounds were identified by GC-MS
      analysis. Ethyl acetate fraction of N. tetragona extract (EFNTE) demonstrated
      good antimicrobial activity (MIC 781 MUg/mL) against 4 strains out of 5. FIC
      index ranged from 0.375 to 1.031 between EFNTE/tylosin and 0.515 to 1.250 between
      EFNTE/streptomycin against S. typhimurium. Among all extracts, EFNTE and butanol
      fraction more significantly inhibited pigment production of C. violaceum.
      Polyphenols were identified as major compound of EFNTE and butanol fraction.
      These results indicate that combination among N. tetragona extract and
      antibiotics could be useful to combat drug-resistance Salmonella infections and
      polyphenols are promising new components from N. tetragona that warrant further
      investigation as a candidate anti-Salmonella agent and quorum sensing inhibitor.

PMID- 24895591
TI  - Current level and correlates of traditional cooking energy sources utilization in
      urban settings in the context of climate change and health, northwest Ethiopia: a
      case of Debre Markos town.
AB  - BACKGROUND: Traditional biomass has been the major source of cooking energy for
      major segment of Ethiopian population for thousands of years. Cognizant of this
      energy poverty, the Government of Ethiopia has been spending huge sum of money to
      increase hydroelectric power generating stations. OBJECTIVE: To assess current
      levels and correlates of traditional cooking energy sources utilization. METHODS:
      A community based cross-sectional study was conducted employing both quantitative
      and qualitative approaches on systematically selected 423 households for
      quantitative and purposively selected 20 people for qualitative parts. SPSS
      version 16 for windows was used to analyze the quantitative data. Logistic
      regression was fitted to assess possible associations and its strength was
      measured using odds ratio at 95% CI. Qualitative data were analyzed thematically.
      RESULT: The study indicated that 95% of households still use traditional biomass
      for cooking. Those who were less knowledgeable about negative health and
      environmental effects of traditional cooking energy sources were seven and six
      times more likely to utilize them compared with those who were knowledgeable (AOR
      (95% CI) = 7.56 (1.635, 34.926), AOR (95% CI) = 6.68 (1.80, 24.385), resp.). The
      most outstanding finding of this study was that people use traditional energy for
      cooking mainly due to lack of the knowledge and their beliefs about food prepared
      using traditional energy. That means "...people still believe that food cooked
      with charcoal is believed to taste delicious than cooked with other means." 
      CONCLUSION: The majority of households use traditional biomass for cooking due to
      lack of knowledge and belief. Therefore, mechanisms should be designed to promote
      electric energy and to teach the public about health effects of traditional
      cooking energy source.

PMID- 24895593
TI  - Figure of image quality and information capacity in digital mammography.
AB  - OBJECTIVES: In this work, a simple technique to assess the image quality
      characteristics of the postprocessed image is developed and an easy to use figure
      of image quality (FIQ) is introduced. This FIQ characterizes images in terms of
      resolution and noise. In addition information capacity, defined within the
      context of Shannon's information theory, was used as an overall image quality
      index. MATERIALS AND METHODS: A digital mammographic image was postprocessed with
      three digital filters. Resolution and noise were calculated via the Modulation
      Transfer Function (MTF), the coefficient of variation, and the figure of image
      quality. In addition, frequency dependent parameters such as the noise power
      spectrum (NPS) and noise equivalent quanta (NEQ) were estimated and used to
      assess information capacity. RESULTS: FIQs for the "raw image" data and the image
      processed with the "sharpen edges" filter were found 907.3 and 1906.1,
      correspondingly. The information capacity values were 60.86 * 10(3) and 78.96 *
      10(3) bits/mm(2). CONCLUSION: It was found that, after the application of the
      postprocessing techniques (even commercial nondedicated software) on the raw
      digital mammograms, MTF, NPS, and NEQ are improved for medium to high spatial
      frequencies leading to resolving smaller structures in the final image.

PMID- 24895592
TI  - Regenerative medicine for the kidney: renotropic factors, renal stem/progenitor
      cells, and stem cell therapy.
AB  - The kidney has the capacity for regeneration and repair after a variety of
      insults. Over the past few decades, factors that promote repair of the injured
      kidney have been extensively investigated. By using kidney injury animal models,
      the role of intrinsic and extrinsic growth factors, transcription factors, and
      extracellular matrix in this process has been examined. The identification of
      renal stem cells in the adult kidney as well as in the embryonic kidney is an
      active area of research. Cell populations expressing putative stem cell markers
      or possessing stem cell properties have been found in the tubules, interstitium,
      and glomeruli of the normal kidney. Cell therapies with bone marrow-derived
      hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells,
      and amniotic fluid-derived stem cells have been highly effective for the
      treatment of acute or chronic renal failure in animals. Embryonic stem cells and
      induced pluripotent stem cells are also utilized for the construction of
      artificial kidneys or renal components. In this review, we highlight the advances
      in regenerative medicine for the kidney from the perspective of renotropic
      factors, renal stem/progenitor cells, and stem cell therapies and discuss the
      issues to be solved to realize regenerative therapy for kidney diseases in
      humans. 

PMID- 24895594
TI  - Xanthan gum as an adjuvant in a subunit vaccine preparation against
      leptospirosis.
AB  - Leptospiral immunoglobulin-like (Lig) proteins are of great interest due to their
      ability to act as mediators of pathogenesis, serodiagnostic antigens, and
      immunogens. Purified recombinant LigA protein is the most promising subunit
      vaccine candidate against leptospirosis reported to date, however, as purified
      proteins are weak immunogens the use of a potent adjuvant is essential for the
      success of LigA as a subunit vaccine. In the present study, we compared xanthan
      pv. pruni (strain 106), aluminium hydroxide (alhydrogel), and CpG ODN as
      adjuvants in a LigA subunit vaccine preparation. Xanthan gum is a high molecular
      weight extracellular polysaccharide produced by fermentation of Xanthomonas spp.,
      a plant-pathogenic bacterium genus. Preparations containing xanthan induced a
      strong antibody response comparable to that observed when alhydrogel was used.
      Upon challenge with a virulent strain of L. interrogans serovar Copenhageni,
      significant protection (Fisher test, P < 0.05) was observed in 100%, 100%, and
      67% of hamsters immunized with rLigANI-xanthan, LigA-CpG-xanthan, and rLigANI
      alhydrogel, respectively. Furthermore, xanthan did not cause cytotoxicity in
      Chinese hamster ovary (CHO) cells in vitro. The use of xanthan as an adjuvant is
      a novel alternative for enhancing the immunogenicity of vaccines against
      leptospirosis and possibly against other pathogens. 

PMID- 24895595
TI  - Glycoprotein IIb/IIIa inhibitors use and outcome after percutaneous coronary
      intervention for non-ST elevation myocardial infarction.
AB  - AIMS: We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors
      on long-term outcomes following percutaneous coronary intervention (PCI) after
      non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that
      these agents are associated with improved short-term outcomes. However, many
      trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies
      yield conflicting results and registry data have suggested that GP IIb/IIIa
      inhibitors may cause more bleeding than what trials indicate. METHODS AND
      RESULTS: This retrospective observational study involves 3047 patients receiving
      dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all
      cause mortality. Major adverse cardiac events (MACE) were a secondary outcome.
      Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were
      younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis
      suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes,
      multivariate analysis (including propensity scoring) showed no benefit for either
      survival (P = 0.136) or MACE (P = 0.614). GP IIb/IIIa inhibitor use was
      associated with an increased risk of major bleeding (P = 0.021). CONCLUSION:
      Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for
      NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk.
      After multivariate adjustment we observed no improvement in MACE or survival and
      an increased risk of major bleeding.

PMID- 24895596
TI  - Effect of mesalamine and prednisolone on TNBS experimental colitis, following
      various doses of orally administered iron.
AB  - BACKGROUND: Experimental data suggest that oral iron (I.) supplementation can
      worsen colitis in animals. AIM: To investigate the influence of various
      concentrations of orally administered I. in normal gut mucosa and mucosa of
      animals with TNBS colitis, as well as the influence of Mesalamine (M.) and
      Prednisolone (P.) on the severity of TNBS colitis following orally administered
      I. METHODS AND MATERIALS: 156 Wistar rats were allocated into 10 groups. Colitis
      was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of
      colitis and extent of tissue damage were assessed histologically. The levels of
      tissue tumor necrosis factor- alpha (t-TNF- alpha ) and tissue malondialdehyde (t
      MDA) were estimated in all animal groups. RESULTS: Moderate and high I.
      supplementation induced inflammation in the healthy colon and increased the
      activity of the experimentally induced TNBS colitis. Administration of M. on TNBS
      colitis following moderate iron supplementation (0.3 g/Kg diet) resulted in a
      significant improvement in the overall histological score as well as in two
      individual histological parameters. M. administration, however, did not
      significantly reduce the t-TNF- alpha levels (17.67 +/- 4.92 versus 14.58 +/-
      5.71, P = 0.102), although it significantly reduced the t-MDA levels (5.79 +/-
      1.55 versus 3.67 +/- 1.39, P = 0.000). Administration of M. on TNBS colitis
      following high iron supplementation (3.0 g/Kg diet) did not improve the overall
      histological score and the individual histological parameters, neither reduced
      the levels of t-TNF- alpha (16.57 +/- 5.61 versus 14.65 +/- 3.88, P = 0.296).
      However, M. significantly reduced the t-MDA levels (5.99 +/- 1.37 versus 4.04 +/-
      1.41, P = 0.000). Administration of P. on TNBS colitis after moderate iron
      supplementation resulted in a significant improvement in the overall histological
      score as well as in three individual histological parameters. P. also resulted in
      a significant reduction in the t-TNF- alpha levels (17.67 +/- 4.92 versus 12.64
      +/- 3.97, P = 0.003) and the t-MDA levels (5.79 +/- 1.54 versus 3.47 +/- 1.21, P
      = 0.001). Administration of P on TNBS colitis after high I. supplementation
      resulted in a significant improvement of the overall histological score and three
      individual histological parameters and significantly reduced the levels of t-TNF-
      alpha (16.6 +/- 5.6 versus 11.85 +/- 1.3, P = 0.001). CONCLUSION: I. can induce
      colonic inflammation and aggravate TNBS colitis. M. and P. can significantly
      improve the inflammatory process in the colonic mucosa in TNBS colitis aggravated
      by orally administered I. P. has a stable anti-TNF- alpha effect. These findings
      suggest that the harmful.

PMID- 24895597
TI  - Significance of soluble lectin-like oxidized LDL receptor-1 levels in systemic
      and coronary circulation in acute coronary syndrome.
AB  - BACKGROUND: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX
      1) level is a novel biomarker for diagnosis of acute coronary syndrome (ACS);
      however, this level in the coronary circulation has yet to be examined. METHODS:
      Twenty-seven consecutive patients with ACS and 40 patients with effort angina
      pectoris (EAP) undergoing percutaneous coronary intervention (PCI) had levels of
      soluble LOX-1 and LOX-1 index measured in paired blood samples from aorta (Ao)
      and coronary sinus (CS) just prior to the PCI. RESULTS: We found positive
      correlations between soluble LOX-1 levels in the Ao and CS in both ACS and EAP
      patients (P < 0.01, for both). The soluble LOX-1 levels in the Ao and CS were
      higher in ACS than in EAP patients (P < 0.01, for both). The levels of soluble
      LOX-1 and LOX-1 index of the CS were significantly greater than those of the Ao
      in both ACS and EAP patients (P < 0.01, for both). Receiver operating
      characteristic curves for ACS detection demonstrated high sensitivity and
      specificity for the soluble LOX-1 and LOX-1 index with no differences between the
      Ao and CS. CONCLUSIONS: The present study showed that circulating soluble LOX-1
      originates from coronary circulation and soluble LOX-1 and LOX-1 index are useful
      biomarkers for ACS.

PMID- 24895600
TI  - 124 Iodine: a longer-life positron emitter isotope-new opportunities in molecular
      imaging.
AB  - (124)Iodine ((124)I) with its 4.2 d half-life is particularly attractive for in
      vivo detection and quantification of longer-term biological and physiological
      processes; the long half-life of (124)I is especially suited for prolonged time
      in vivo studies of high molecular weight compounds uptake. Numerous small
      molecules and larger compounds like proteins and antibodies have been
      successfully labeled with (124)I. Advances in radionuclide production allow the
      effective availability of sufficient quantities of (124)I on small biomedical
      cyclotrons for molecular imaging purposes. Radioiodination chemistry with (124)I
      relies on well-established radioiodine labeling methods, which consists mainly in
      nucleophilic and electrophilic substitution reactions. The physical
      characteristics of (124)I permit taking advantages of the higher PET image
      quality. The availability of new molecules that may be targeted with (124)I
      represents one of the more interesting reasons for the attention in nuclear
      medicine. We aim to discuss all iodine radioisotopes application focusing on
      (124)I, which seems to be the most promising for its half-life, radiation
      emissions, and stability, allowing several applications in oncological and
      nononcological fields.

PMID- 24895598
TI  - Plasmid transfer of plasminogen K1-5 reduces subcutaneous hepatoma growth by
      affecting inflammatory factors.
AB  - There is evidence that plasminogen K1-5 (PlgK1-5) directly affects tumour cells
      and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on
      hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects
      of plasmid encoding PlgK1-5 (pK1-5) on Hepa129, Hepa1-6, and HuH7 cell viability,
      apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3
      phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel
      density, and effects on vascular endothelial growth factor (VEGF) and tumour
      necrosis factor alpha (TNF-alpha) expression were examined following treatment
      with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up
      to 15% compared to the corresponding controls. Proliferation was not affected.
      VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with
      pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous
      tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel
      density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were
      increased, whereas VEGF levels in tumours and livers were reduced after pK1-5
      treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma
      (cell) growth not only by reducing vessel density but also by inducing apoptosis,
      inhibiting proliferation, and triggering inflammation. 

PMID- 24895599
TI  - Salvage radiosurgery for selected patients with recurrent malignant gliomas.
AB  - PURPOSE: To analyse the survival after salvage radiosurgery and to identify
      prognostic factors. METHODS: We retrospectively reviewed 87 consecutive patients,
      with recurrent high-grade glioma, that underwent stereotactic radiosurgery
      between 1997 and 2010. We evaluated the survival after initial diagnosis and
      after reirradiation. The prognostic factors were analysed by bivariate and
      multivariate Cox regression model. RESULTS: The median age was 48 years old. The
      primary histology included anaplastic astrocytoma (47%) and glioblastoma (53%). A
      margin dose of 18 Gy was administered in the majority of cases (74%). The median
      survival after initial diagnosis was 21 months (39 months for anaplastic
      astrocytoma and 18.5 months for glioblastoma) and after reirradiation it was 10
      months (17 months for anaplastic astrocytoma and 7.5 months for glioblastoma). In
      the bivariate analyses, the prognostic factors significantly associated with
      survival after reirradiation were age, tumour and treatment volume at recurrence,
      recursive partitioning analyses classification, Karnofsky performance score,
      histology, and margin to the planning target volume. Only the last four showed
      significant association in the multivariate analyses. CONCLUSION: stereotactic
      radiosurgery is a safe and may be an effective treatment option for selected
      patients diagnosed with recurrent high-grade glioma. The identified prognostic
      factors could help individualise the treatment.

PMID- 24895601
TI  - Multiple regression analysis of mRNA-miRNA associations in colorectal cancer
      pathway.
AB  - BACKGROUND: MicroRNA (miRNA) is a short and endogenous RNA molecule that
      regulates posttranscriptional gene expression. It is an important factor for
      tumorigenesis of colorectal cancer (CRC), and a potential biomarker for
      diagnosis, prognosis, and therapy of CRC. Our objective is to identify the
      related miRNAs and their associations with genes frequently involved in CRC
      microsatellite instability (MSI) and chromosomal instability (CIN) signaling
      pathways. RESULTS: A regression model was adopted to identify the significantly
      associated miRNAs targeting a set of candidate genes frequently involved in
      colorectal cancer MSI and CIN pathways. Multiple linear regression analysis was
      used to construct the model and find the significant mRNA-miRNA associations. We
      identified three significantly associated mRNA-miRNA pairs: BCL2 was positively
      associated with miR-16 and SMAD4 was positively associated with miR-567 in the
      CRC tissue, while MSH6 was positively associated with miR-142-5p in the normal
      tissue. As for the whole model, BCL2 and SMAD4 models were not significant, and
      MSH6 model was significant. The significant associations were different in the
      normal and the CRC tissues. CONCLUSION: Our results have laid down a solid
      foundation in exploration of novel CRC mechanisms, and identification of miRNA
      roles as oncomirs or tumor suppressor mirs in CRC.

PMID- 24895602
TI  - Three consecutive days of interval runs to exhaustion affects lymphocyte subset
      apoptosis and migration.
AB  - This investigation assessed the lymphocyte subset response to three days of
      intermittent run exercise to exhaustion. Twelve healthy college-aged males (n =
      8) and females (n = 4) (age = 26 +/- 4 years; height = 170.2 +/- 10 cm; body mass
      = 75 +/- 18 kg) completed an exertion test (maximal running speed and VO2max) and
      later performed three consecutive days of an intermittent run protocol to
      exhaustion (30 sec at maximal running speed and 30 sec at half of the maximal
      running speed). Blood was collected before exercise (PRE) and immediately
      following the treadmill bout (POST) each day. When the absolute change from
      baseline was evaluated (i. e., Delta baseline), a significant change in CD4+ and
      CD8+ for CX3CR1 cells was observed by completion of the third day. Significant
      changes in both apoptosis and migration were observed following two consecutive
      days in CD19+ lymphocytes, and the influence of apoptosis persisted following the
      third day. Given these lymphocyte responses, it is recommended that a rest day be
      incorporated following two consecutive days of a high-intensity intermittent run
      program to minimize immune cell modulations and reduce potential susceptibility.

PMID- 24895603
TI  - Habitual coffee consumption enhances attention and vigilance in hemodialysis
      patients.
AB  - OBJECTIVE: Coffee drinking is the main source of caffeine intake among adult
      population in the western world. It has been reported that low to moderate
      caffeine intake has beneficial effect on alertness and cognitive functions in
      healthy subjects. The aim of this study is to evaluate the impact of habitual
      coffee consumption on cognitive function in hemodialysis patients. METHODS: In a
      cross-sectional study, 86 patients from a single-dialysis centre underwent
      assessment by the Montreal Cognitive Assessment tool and evaluation for symptoms
      of fatigue, mood, and sleep disorders by well-validated questionnaires. The
      habitual coffee use and the average daily caffeine intake were estimated by
      participants' response to a dietary questionnaire. RESULTS: Sixty-seven subjects
      (78%) consumed black coffee daily, mostly in low to moderate dose. Cognitive
      impairment was found in three-quarters of tested patients. Normal mental
      performance was more often in habitual coffee users (25% versus 16%). Regular
      coffee drinkers achieved higher mean scores on all tested cognitive domains, but
      a significant positive correlation was found only for items that measure
      attention and concentration (P = 0.024). CONCLUSIONS: Moderate caffeine intake by
      habitual coffee consumption could have beneficial impact on cognitive function in
      hemodialysis patients due to selective enhancement of attention and vigilance.

PMID- 24895604
TI  - Antioxidant defense enzyme genes and asthma susceptibility: gender-specific
      effects and heterogeneity in gene-gene interactions between pathogenetic variants
      of the disease.
AB  - Oxidative stress resulting from an increased amount of reactive oxygen species
      and an imbalance between oxidants and antioxidants plays an important role in the
      pathogenesis of asthma. The present study tested the hypothesis that genetic
      susceptibility to allergic and nonallergic variants of asthma is determined by
      complex interactions between genes encoding antioxidant defense enzymes (ADE). We
      carried out a comprehensive analysis of the associations between adult asthma and
      46 single nucleotide polymorphisms of 34 ADE genes and 12 other candidate genes
      of asthma in Russian population using set association analysis and multifactor
      dimensionality reduction approaches. We found for the first time epistatic
      interactions between ADE genes underlying asthma susceptibility and the genetic
      heterogeneity between allergic and nonallergic variants of the disease. We
      identified GSR (glutathione reductase) and PON2 (paraoxonase 2) as novel
      candidate genes for asthma susceptibility. We observed gender-specific effects of
      ADE genes on the risk of asthma. The results of the study demonstrate complexity
      and diversity of interactions between genes involved in oxidative stress
      underlying susceptibility to allergic and nonallergic asthma. 

PMID- 24895605
TI  - Timing embryo segmentation: dynamics and regulatory mechanisms of the vertebrate
      segmentation clock.
AB  - All vertebrate species present a segmented body, easily observed in the
      vertebrate column and its associated components, which provides a high degree of
      motility to the adult body and efficient protection of the internal organs. The
      sequential formation of the segmented precursors of the vertebral column during
      embryonic development, the somites, is governed by an oscillating genetic
      network, the somitogenesis molecular clock. Herein, we provide an overview of the
      molecular clock operating during somite formation and its underlying molecular
      regulatory mechanisms. Human congenital vertebral malformations have been
      associated with perturbations in these oscillatory mechanisms. Thus, a better
      comprehension of the molecular mechanisms regulating somite formation is required
      in order to fully understand the origin of human skeletal malformations. 

PMID- 24895607
TI  - Application of proteomics and peptidomics to COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex disorder involving both
      airways and lung parenchyma, usually associated with progressive and poorly
      reversible airflow limitation. In order to better characterize the phenotypic
      heterogeneity and the prognosis of patients with COPD, there is currently an
      urgent need for discovery and validation of reliable disease biomarkers. Within
      this context, proteomic and peptidomic techniques are emerging as very valuable
      tools that can be applied to both systemic and pulmonary samples, including
      peripheral blood, induced sputum, exhaled breath condensate, bronchoalveolar
      lavage fluid, and lung tissues. Identification of COPD biomarkers by means of
      proteomic and peptidomic approaches can thus also lead to discovery of new
      molecular targets potentially useful to improve and personalize the therapeutic
      management of this widespread respiratory disease. 

PMID- 24895608
TI  - Bond strengths of silorane- and methacrylate-based composites to various
      underlying materials.
AB  - OBJECTIVE: To evaluate shear bond strength (SBS) values of a methacrylate (FZ
      250) and a silorane-based (FS) resin composite to various underlying materials.
      MATERIALS AND METHODS: A total of 80 samples were prepared with four different
      underlying materials; a flowable (FLC) and a bulk-fill flowable composite (BFC),
      and a conventional (CGIC) and resin modified glass-ionomer cement (RMGIC). These
      underlying materials were laminated plus to methacrylate or silorane-based resin
      composites (n = 10). To evaluate the specimens SBS values were evaluated with a
      universal testing machine (cross-head speed; 1.0 mm/min). Statistical comparisons
      were carried out using two-way ANOVA and Tukey's post hoc test with a
      significance level of P < 0.05. RESULTS: SBS values for FZ250 were significantly
      higher than for FS for all of the underlying materials tested (P < 0.05). SBS
      values of FZ250 to BFC were significantly higher than to all other materials (P <
      0.05), whereas SBS values of FS did not vary significantly according to
      underlying material (P > 0.05). CONCLUSION: The use of FS in conjunction with any
      of the tested materials showed lower SBS than the FZ 250. Also, new low elastic
      modulus liner BFC presented slightly good interfacial adhesion so, the usage of
      BFC as an underlying material may be preferable for FZ 250.

PMID- 24895609
TI  - Glucagon effects on 3H-histamine uptake by the isolated guinea-pig heart during
      anaphylaxis.
AB  - We estimated the influence of acute glucagon applications on (3)H-histamine
      uptake by the isolated guinea-pig heart, during a single (3)H-histamine passage
      through the coronary circulation, before and during anaphylaxis, and the
      influence of glucagon on level of histamine, NO, O2 (-), and H2O2 in the venous
      effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not
      change (3)H-histamine Umax and the level of endogenous histamine. At the same
      time, in the presence of glucagon, (3)H-histamine Unet is increased and backflux
      is decreased when compared to the corresponding values in the absence of
      glucagon. During anaphylaxis, in the presence of glucagon, the values of (3)H
      histamine Umax and Unet are significantly higher and backflux is significantly
      lower in the presence of glucagon when compared to the corresponding values in
      the absence of glucagon. The level of endogenous histamine during anaphylaxis in
      the presence of glucagon (6.9-7.38 * 10(-8) MUM) is significantly lower than the
      histamine level in the absence of glucagon (10.35-10.45 * 10(-8) MUM). Glucagon
      pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in
      comparison with the period before glucagon administration (2.49 nmol/mL). Then,
      in the presence of glucagon, O2 (-) level fails to increase during anaphylaxis.
      Also, our results show no significant differences in H2O2 levels before, during,
      and after anaphylaxis in the presence of glucagon, but these values are
      significantly lower than the corresponding values in the absence of glucagon. In
      conclusion, our results show that glucagon increases NO release and prevents the
      increased release of free radicals during anaphylaxis, and decreases histamine
      level in the venous effluent during cardiac anaphylaxis, which may be a
      consequence of decreased histamine release and/or intensified histamine capturing
      by the heart during anaphylaxis.

PMID- 24895610
TI  - The use of hyaluronic acid after tendon surgery and in tendinopathies.
AB  - Viscosupplementation with hyaluronic acid is safe and effective in the management
      of osteoarthritis, but its use in the treatment of tendon disorders has received
      less attention. The aim of this review is to summarize the current knowledge on
      this topic, evaluating experimental and clinical trials. A search of English
      language articles was performed using the key search terms "hyaluronic acid" or
      "viscosupplementation" combined with "tendon," "tendinopathy," "adhesions," or
      "gliding," independently. In quite all the experimental studies, performed after
      surgical procedures for tendon injuries or in the treatment of chronic
      tendinopathies, using different hyaluronic acid compounds, positive results
      (reduced formation of scars and granulation tissue after tendon repair, less
      adhesions and gliding resistance, and improved tissue healing) were observed. In
      a limited number of cases, hyaluronic acid has been employed in clinical
      practice. After flexor tendon surgery, a greater total active motion and fingers
      function, with an earlier return to work and daily activities, were observed.
      Similarly, in patients suffering from elbow, patellar, and shoulder tendons
      disorders, pain was reduced, and function improved. The positive effect of
      hyaluronic acid can be attributed to the anti-inflammatory activity, enhanced
      cell proliferation, and collagen deposition, besides the lubricating action on
      the sliding surface of the tendon. 

PMID- 24895611
TI  - The copper radioisotopes: a systematic review with special interest to 64Cu.
AB  - Copper (Cu) is an important trace element in humans; it plays a role as a
      cofactor for numerous enzymes and other proteins crucial for respiration, iron
      transport, metabolism, cell growth, and hemostasis. Natural copper comprises two
      stable isotopes, (63)Cu and (65)Cu, and 5 principal radioisotopes for molecular
      imaging applications ((60)Cu, (61)Cu, (62)Cu, and (64)Cu) and in vivo targeted
      radiation therapy ((64)Cu and (67)Cu). The two potential ways to produce Cu
      radioisotopes concern the use of the cyclotron or the reactor. A noncopper target
      is used to produce noncarrier-added Cu thanks to a chemical separation from the
      target material using ion exchange chromatography achieving a high amount of
      radioactivity with the lowest possible amount of nonradioactive isotopes. In
      recent years, Cu isotopes have been linked to antibodies, proteins, peptides, and
      nanoparticles for preclinical and clinical research; pathological conditions that
      influence Cu metabolism such as Menkes syndrome, Wilson disease, inflammation,
      tumor growth, metastasis, angiogenesis, and drug resistance have been studied. We
      aim to discuss all Cu radioisotopes application focusing on (64)Cu and in
      particular its form (64)CuCl2 that seems to be the most promising for its half
      life, radiation emissions, and stability with chelators, allowing several
      applications in oncological and nononcological fields.

PMID- 24895606
TI  - Side effects of radiographic contrast media: pathogenesis, risk factors, and
      prevention.
AB  - Radiocontrast media (RCM) are medical drugs used to improve the visibility of
      internal organs and structures in X-ray based imaging techniques. They may have
      side effects ranging from itching to a life-threatening emergency, known as
      contrast-induced nephropathy (CIN). We define CIN as acute renal failure
      occurring within 24-72 hrs of exposure to RCM that cannot be attributed to other
      causes. It usually occurs in patients with preexisting renal impairment and
      diabetes. The mechanisms underlying CIN include reduction in medullary blood flow
      leading to hypoxia and direct tubule cell damage and the formation of reactive
      oxygen species. Identification of patients at high risk for CIN is important. We
      have reviewed the risk factors and procedures for prevention, providing a long
      list of references enabling readers a deep evaluation of them both. The first
      rule to follow in patients at risk of CIN undergoing radiographic procedure is
      monitoring renal function by measuring serum creatinine and calculating the eGFR
      before and once daily for 5 days after the procedure. It is advised to
      discontinue potentially nephrotoxic medications, to choose radiocontrast media at
      lowest dosage, and to encourage oral or intravenous hydration. In high-risk
      patients N-acetylcysteine may also be given. 

PMID- 24895613
TI  - Comparison of selected kinematic facebows applied to mandibular tracing.
AB  - The study focused on the comparison between mechanical and computerized
      registration methods used by the two selected kinematic facebows. The material
      consisted of 35 women aged 18 to 35, studied using the Gerber Dynamic Facebow and
      the computerized ARCUSdigma II axiograph. To compare the devices the condylar
      path inclination (CPI) was recorded according to the Camper's line, enabling the
      acquisition of easily comparable values based on which the devices were
      objectively and subjectively analyzed. Statistics was performed for the obtained
      data. The study showed that the values for the CPI registrated by the ARCUSdigma
      II are significantly higher than those obtained by using the Gerber Dynamic
      Facebow. The significant difference in the records of the CPI is most likely a
      result of the differences in the registration techniques assumptions. ARCUSdigma
      II provides the user with more diagnostic options than Gerber Dynamic Facebow.
      Mechanical facebow handling has a higher risk of hand-measuring errors in tracing
      procedure. Due to high discrepancy of achieved results from different systems the
      authors recommend to use articulator compatible with facebow whose measurement
      has been done. 

PMID- 24895612
TI  - Evaluating the cancer therapeutic potential of cardiac glycosides.
AB  - Cardiac glycosides, also known as cardiotonic steroids, are a group of natural
      products that share a steroid-like structure with an unsaturated lactone ring and
      the ability to induce cardiotonic effects mediated by a selective inhibition of
      the Na(+)/K(+)-ATPase. Cardiac glycosides have been used for many years in the
      treatment of cardiac congestion and some types of cardiac arrhythmias. Recent
      data suggest that cardiac glycosides may also be useful in the treatment of
      cancer. These compounds typically inhibit cancer cell proliferation at nanomolar
      concentrations, and recent high-throughput screenings of drug libraries have
      therefore identified cardiac glycosides as potent inhibitors of cancer cell
      growth. Cardiac glycosides can also block tumor growth in rodent models, which
      further supports the idea that they have potential for cancer therapy. Evidence
      also suggests, however, that cardiac glycosides may not inhibit cancer cell
      proliferation selectively and the potent inhibition of tumor growth induced by
      cardiac glycosides in mice xenografted with human cancer cells is probably an
      experimental artifact caused by their ability to selectively kill human cells
      versus rodent cells. This paper reviews such evidence and discusses experimental
      approaches that could be used to reveal the cancer therapeutic potential of
      cardiac glycosides in preclinical studies. 

PMID- 24895615
TI  - Perilipin expression reveals adipogenic potential of hADSCs inside superporous
      polymeric cellular delivery systems.
AB  - Recent progress in tissue engineering and regenerative medicine envisages the use
      of cell-scaffold bioconstructs to best mimic the natural in vivo
      microenvironment. Our aim was not only to develop novel 3D porous scaffolds for
      regenerative applications by the association of gelatin (G), alginate (A), and
      polyacrylamide (PAA) major assets but also to evaluate their in vitro potential
      to support human adipose-derived stem cells (hADSCs) adipogenesis. G-A-PAA
      biomatrix investigated in this work is an interesting substrate combining the
      advantages of the three individual constituents, namely, biodegradability of G,
      hydrophilicity of A and PAA, superior elasticity at compression with respect to
      the G-A and PAA controls, and the capacity to generate porous scaffolds. hADSCs
      inside these novel interpenetrating polymer networks (IPNs) were able to populate
      the entire scaffold structure and to display their characteristic spindle-like
      shape as a consequence of a good interaction with G component of the matrices.
      Additionally, hADSCs proved to display the capacity to differentiate towards
      mature adipocytes, to accumulate lipids inside their cytoplasm, and to express
      perilipin late adipogenic marker inside novel IPNs described in this study. On
      long term, this newly designed biomatrix aims to represent a stem cell delivery
      system product dedicated for modern regenerative strategies. 

PMID- 24895614
TI  - Macrophages and Leydig cells in testicular biopsies of azoospermic men.
AB  - A number of studies have indicated that testicular macrophages play an important
      role in regulating steroidogenesis of Leydig cells and maintain homeostasis
      within the testis. The current paper deals with macrophages (CD68 positive cells)
      and Leydig cells in patients with nonobstructive azoospermia (NOA). Methods
      employed included histological analysis on semi- and ultrathin sections,
      immunohistochemistry, morphometry, and hormone analysis in the blood serum.
      Histological analysis pointed out certain structural changes of macrophages and
      Leydig cells in NOA group of patients when compared to controls. In the testis
      interstitium, an increased presence of CD68 positive cells has been noted. Leydig
      cells in NOA patients displayed a kind of a mosaic picture across the same
      bioptic sample: both normal and damaged Leydig cells with pronounced
      vacuolisation and various intensity of expression of testosterone have been
      observed. Stereological analysis indicated a significant increase in volume
      density of both CD68 positive and vacuolated Leydig cells and a positive
      correlation between the volume densities of these cell types. The continuous
      gonadotropin overstimulation of Leydig cells, together with a negative paracrine
      action of macrophages, could result in the damage of steroidogenesis and deficit
      of testosterone in situ. 

PMID- 24895616
TI  - Hip reconstruction osteotomy by Ilizarov method as a salvage option for abnormal
      hip joints.
AB  - Hip joint instability can be secondary to congenital hip pathologies like
      developmental dysplasia (DDH) or acquired such as sequel of infective or
      neoplastic process. An unstable hip is usually associated with loss of bone from
      the proximal femur, proximal migration of the femur, lower-extremity length
      discrepancy, abnormal gait, and pain. In this case series of 37 patients coming
      to our institution between May 2005 and December 2011, we report our results in
      treatment of unstable hip joint by hip reconstruction osteotomy using the
      Ilizarov method and apparatus. This includes an acute valgus and extension
      osteotomy of the proximal femur combined with gradual varus and distraction (if
      required) for realignment and lengthening at a second, more distal, femoral
      osteotomy. 18 males and 19 females participated in the study. There were 17
      patients with DDH, 12 with sequelae of septic arthritis, 2 with tuberculous
      arthritis, 4 with posttraumatic arthritis, and 2 with focal proximal femoral
      deficiency. Outcomes were evaluated by using Harris Hip Scoring system. At the
      mean follow-up of 37 months, Harris Hip Score had significantly improved in all
      patients. To conclude, illizarov hip reconstruction can successfully improve
      Trendelenburg's gait. It supports the pelvis and simultaneously restores knee
      alignment and corrects lower-extremity length discrepancy (LLD).

PMID- 24895617
TI  - Quantitative evaluation of the severity of acute illness in adult patients with
      tick-borne encephalitis.
AB  - The aim of the present study was to quantify the severity of acute illness in
      patients with tick-borne encephalitis and to ascertain this approach by comparing
      it to standard clinical assessment. We designed scoring system for quantification
      of the severity of acute illness in patients with tick-borne encephalitis.
      Certain number of points was allotted to the presence, intensity, and duration of
      individual symptoms/signs. According to the obtained score the disease was
      classified as mild, moderate, and severe. Tick-borne encephalitis was assessed
      clinically as mild when only signs/symptoms of meningeal involvement were found,
      moderate in case of monofocal neurological signs and/or mild to moderate
      signs/symptoms of central nervous system dysfunction, and severe in patients with
      multifocal neurological signs and/or symptoms of severe dysfunction of central
      nervous system. By designed scoring system 282 adult patients, 146 males and 136
      females, average aged 52.2 +/- 15.5 years (range 15-82 years), with confirmed
      tick-borne encephalitis, were prospectively assessed. In 279/282 (98.9%) patients
      the severity according to clinical assessment matched with the score ranges for
      mild, moderate, and severe disease. The proposed approach enables precise and
      straightforward appraisal of the severity of acute illness and could be useful
      for comparison of findings within/between study groups.

PMID- 24895618
TI  - Construction and characterization of a bacterial artificial chromosome library
      for the hexaploid wheat line 92R137.
AB  - For map-based cloning of genes conferring important traits in the hexaploid wheat
      line 92R137, a bacterial artificial chromosome (BAC) library, including two
      sublibraries, was constructed using the genomic DNA of 92R137 digested with
      restriction enzymes HindIII and BamHI. The BAC library was composed of total
      765,696 clones, of which 390,144 were from the HindIII digestion and 375,552 from
      the BamHI digestion. Through pulsed-field gel electrophoresis (PFGE) analysis of
      453 clones randomly selected from the HindIII sublibrary and 573 clones from the
      BamHI sublibrary, the average insert sizes were estimated as 129 and 113 kb,
      respectively. Thus, the HindIII sublibrary was estimated to have a 3.01-fold
      coverage and the BamHI sublibrary a 2.53-fold coverage based on the estimated
      hexaploid wheat genome size of 16,700 Mb. The 765,696 clones were arrayed in
      1,994 384-well plates. All clones were also arranged into plate pools and further
      arranged into 5-dimensional (5D) pools. The probability of identifying a clone
      corresponding to any wheat DNA sequence (such as gene Yr26 for stripe rust
      resistance) from the library was estimated to be more than 99.6%. Through
      polymerase chain reaction screening the 5D pools with Xwe173, a marker tightly
      linked to Yr26, six BAC clones were successfully obtained. These results
      demonstrate that the BAC library is a valuable genomic resource for positional
      cloning of Yr26 and other genes of interest.

PMID- 24895619
TI  - Biomarkers of mercury exposure in the Amazon.
AB  - Mercury exposure in the Amazon has been studied since the 1980s decade and the
      assessment of human mercury exposure in the Amazon is difficult given that the
      natural occurrence of this metal is high and the concentration of mercury in
      biological samples of this population exceeds the standardized value of normality
      established by WHO. Few studies have focused on the discovery of mercury
      biomarkers in the region's population. In this way, some studies have used
      genetics as well as immunological and cytogenetic tools in order to find a
      molecular biomarker for assessing the toxicological effect of mercury in the
      Amazonian population. Most of those studies focused attention on the relation
      between mercury exposure and autoimmunity and, because of that, they will be
      discussed in more detail. Here we introduce the general aspects involved with
      each biomarker that was studied in the region in order to contextualize the
      reader and add information about the Amazonian life style and health that may be
      considered for future studies. We hope that, in the future, the toxicological
      studies in this field use high technological tools, such as the next generation
      sequencing and proteomics skills, in order to comprehend basic questions
      regarding the metabolic route of mercury in populations that are under constant
      exposure, such as in the Amazon. 

PMID- 24895620
TI  - Antagonistic interactions of "Ya-Sa-Marn-Phlae" ethanol extract in combination
      with topical antiseptics against clinical isolates of Staphylococcus aureus.
AB  - This investigation was aimed at assessing a possible interaction of a traditional
      Thai herbal recipe, "Ya-Sa-Marn-Phlae (YSMP)," used for wound treatments with
      topical antiseptics, povidone-iodine (PI) solution and hydrogen peroxide (H2O2),
      and effects of THR-SK010 alone and the combinations on Staphylococcus aureus.
      Antibacterial activities of ethanol extracts from the herbal recipe were
      determined against both methicillin resistant Staphylococcus aureus (MRSA) and
      methicillin-susceptible S. aureus (MSSA). YSMP exhibited remarkable
      antistaphylococcal activity with MIC values of 3.9-7.8 MUg/mL. This recipe
      possessed bacteriostatic activity and did not reduce the tolerance of both MRSA
      and MSSA isolates to the high ionic strength. Interaction between THR-SK010 and
      the antiseptics was carried out by checkerboard testing and time-kill assay. Both
      indifferent and slightly antagonistic effects were observed with THR-SK010/PI and
      THR-SK010/H2O2 combinations against the tested isolates. In addition to
      commercially available antiseptics, THR-SK010 offered additional therapeutic
      options for the decolonization of MRSA and MSSA. Topical application of plant
      extracts with antioxidant activity, such as THR-SK010, should not be used
      immediately with PI or H2O2 and further investigation on this interaction is
      needed.

PMID- 24895621
TI  - A reliable method for rhythm analysis during cardiopulmonary resuscitation.
AB  - Interruptions in cardiopulmonary resuscitation (CPR) compromise defibrillation
      success. However, CPR must be interrupted to analyze the rhythm because although
      current methods for rhythm analysis during CPR have high sensitivity for
      shockable rhythms, the specificity for nonshockable rhythms is still too low.
      This paper introduces a new approach to rhythm analysis during CPR that combines
      two strategies: a state-of-the-art CPR artifact suppression filter and a shock
      advice algorithm (SAA) designed to optimally classify the filtered signal.
      Emphasis is on designing an algorithm with high specificity. The SAA includes a
      detector for low electrical activity rhythms to increase the specificity, and a
      shock/no-shock decision algorithm based on a support vector machine classifier
      using slope and frequency features. For this study, 1185 shockable and 6482
      nonshockable 9-s segments corrupted by CPR artifacts were obtained from 247
      patients suffering out-of-hospital cardiac arrest. The segments were split into a
      training and a test set. For the test set, the sensitivity and specificity for
      rhythm analysis during CPR were 91.0% and 96.6%, respectively. This new approach
      shows an important increase in specificity without compromising the sensitivity
      when compared to previous studies. 

PMID- 24895622
TI  - 7-Tesla magnetic resonance imaging precisely and noninvasively reflects
      inflammation and remodeling of the skeletal muscle in a mouse model of
      antisynthetase syndrome.
AB  - Inflammatory myopathies comprise heterogeneous disorders. Their etiopathogenesis
      is poorly understood, because of the paucity of informative experimental models
      and of approaches for the noninvasive study of inflamed tissues. Magnetic
      resonance imaging (MRI) provides information about the state of the skeletal
      muscle that reflects various facets of inflammation and remodeling. This
      technique has been scarcely used in experimental models of inflammatory
      myopathies. We characterized the performance of MRI in a well-established mouse
      model of myositis and the antisynthetase syndrome, based on the immunization of
      wild-type mice with the amino-terminal fragment of histidyl-tRNA synthetase
      (HisRS). Over an eight-week period following myositis induction, MRI enabled
      precise identification of pathological events taking place in muscle tissue.
      Areas of edema and of active inflammation identified by histopathology paralleled
      muscle modifications detected noninvasively by MRI. Muscles changes were
      chronologically associated with the establishment of autoimmunity, as reflected
      by the development of anti-HisRS antibodies in the blood of immunized mice. MR
      imaging easily appreciated muscle damage and remodeling even if actual disruption
      of myofiber integrity (as assessed by serum concentrations of creatinine
      phosphokinase) was limited. Thus, MR imaging represents an informative and
      noninvasive analytical tool for studying in vivo immune-mediated muscle
      involvement. 

PMID- 24895623
TI  - Bioactive compounds derived from the yeast metabolism of aromatic amino acids
      during alcoholic fermentation.
AB  - Metabolites resulting from nitrogen metabolism in yeast are currently found in
      some fermented beverages such as wine and beer. Their study has recently
      attracted the attention of researchers. Some metabolites derived from aromatic
      amino acids are bioactive compounds that can behave as hormones or even mimic
      their role in humans and may also act as regulators in yeast. Although the
      metabolic pathways for their formation are well known, the physiological
      significance is still far from being understood. The understanding of this
      relevance will be a key element in managing the production of these compounds
      under controlled conditions, to offer fermented food with specific enrichment in
      these compounds or even to use the yeast as nutritional complements. 

PMID- 24895625
TI  - Classification of epidemic community-acquired methicillin-resistant
      Staphylococcus aureus by anatomical site of isolation.
AB  - Methicillin-resistant Staphylococcus aureus contributes significantly to cost,
      morbidity, and mortality due to infectious disease. We surveyed community
      associated MRSA isolates to determine which strains were present within
      anatomical sites of interest. The most likely sources of MRSA among anatomic
      sites swabbed were wounds followed by the nasal cavity. The USA 300 MRSA strain
      was most commonly isolated among wound infections while nasal swabs largely
      yielded USA 100 MRSA. The frequency of isolation of USA 100 amongst community
      associated strains is clinically significant as this strain is often correlated
      with invasive disease, exhibits broad antibiotic resistance, and has been
      considered to be hospital associated. The potential of USA 100 to cause serious
      disease and the frequency of its isolation suggest an important reservoir for
      opportunistic infection. These data demonstrate that MRSA epidemic clones are
      widespread among the community. 

PMID- 24895624
TI  - Acoustic radiation force impulse elastography for efficacy evaluation after
      hepatocellular carcinoma radiofrequency ablation: a comparative study with
      contrast-enhanced ultrasound.
AB  - AIM: To explore acoustic radiation force impulse (ARFI) elastography in assessing
      residual tumors of hepatocellular carcinoma (HCC) after radiofrequency ablation
      (RFA). MATERIALS AND METHODS: There were 83 HCC lesions among 72 patients. All
      patients were examined with ARFI, contrast enhanced ultrasound (CEUS), and CT or
      MRI. Tumor brightness on virtual touch tissue imaging (VTI) and shear wave
      velocity (SWV) were assessed before and approximately one month after RFA.
      RESULTS: There were 14 residual tumors after RFA. VTI showed that all the tumors
      were darker after RFA. VTI was not able to distinguish the ablated lesions and
      the residual tumors. 13 residual tumor lesions were detected by CEUS. All
      completely ablated nodules had SWV demonstration of x.xx., while with those
      residual nodules, 6 tumors had x.xx measurement and 8 tumors had measurable SWV.
      nine lesions with residual tumors occurred in cirrhosis subjects and 5 lesions
      with residual tumors occurred in fibrosis subjects; there was no residual tumor
      in the normal liver subjects. CONCLUSION: VTI technique cannot demonstrate
      residual tumor post RFA. While SWV measurement of less than x.xx is likely
      associated with residual tumors, measurement of less than x.xx cannot exclude
      residual tumors. Liver cirrhosis is associated with decreased chance of a
      complete ablation.

PMID- 24895628
TI  - High-intensity physical training in the treatment of chronic diseases and
      disorders.

PMID- 24895626
TI  - Reduction-triggered breakable micelles of amphiphilic polyamide amine-g
      polyethylene glycol for methotrexate delivery.
AB  - Reduction-triggered breakable polymeric micelles incorporated with MTX were
      prepared using amphiphilic PAA-g-PEG copolymers having S-S bonds in the backbone.
      The micelles were spherical with diameters less than 70 nm. The micelles could
      encapsulate the hydrophobic MTX in the hydrophobic core. The drug loading content
      and drug loading efficiency of the micelles were highly dependent on the
      copolymer chemical structure, ranging from 2.9 to 7.5% and 31.9 to 82.5%,
      respectively. Both the drug loading content and drug loading efficiency increased
      along with more hydrophobic segments in the copolymers. In normal circumstance,
      these micelles were capable of keeping stable and hold most of the MTX in the
      core, stabilizing the incorporated MTX through the pi-pi stacking with the phenyl
      groups in the backbone of the copolymers. In reductive environments that mimicked
      the intracellular compartments, the entire MTX payload could be quickly released
      due to the reduction-triggered breakage of the micelles. These micelles showed
      good antiproliferative activity against several cancer cell lines, including KB,
      4T-1 and HepG2, especially within the low drug concentration scope.

PMID- 24895627
TI  - Kinematic metrics based on the virtual reality system Toyra as an assessment of
      the upper limb rehabilitation in people with spinal cord injury.
AB  - The aim of this study was to develop new strategies based on virtual reality that
      can provide additional information to clinicians for the rehabilitation
      assessment. Virtual reality system Toyra has been used to record kinematic
      information of 15 patients with cervical spinal cord injury (SCI) while
      performing evaluation sessions using the mentioned system. Positive correlation,
      with a moderate and very strong association, has been found between clinical
      scales and kinematic data, considering only the subscales more closely related to
      the upper limb function. A set of metrics was defined combining these kinematic
      data to obtain parameters of reaching amplitude, joint amplitude, agility,
      accuracy, and repeatability during the evaluation sessions of the virtual reality
      system Toyra. Strong and moderate correlations have been also found between the
      metrics reaching and joint amplitude and the clinical scales. 

PMID- 24895629
TI  - Frequency of piroplasms Babesia microti and Cytauxzoon felis in stray cats from
      northern Italy.
AB  - Emerging diseases caused by piroplasms pose a health risk for man and other
      animals, and domestic cats have been proposed as potential reservoirs for some
      piroplasm infections. The aim of this study was to identify the frequency of the
      piroplasms Babesia microti and Cytauxzoon felis in stray cats from northern Italy
      and to identify possible risk factors associated with these infections. Blood
      samples from 260 stray cats enrolled in a trap-neuter-release (TNR) program in
      northern Italy were examined with conventional PCR for the presence of Babesia
      microti and Cytauxzoon felis DNA. No sample (0.0%) tested positive for C. felis,
      whilst B. microti DNA was detected in two samples (0.8%). Both infected cats were
      in good clinical condition and recovered well from the neutering surgery. One of
      these two cats had a triple coinfection with Babesia microti, Candidatus
      Mycoplasma haemominutum, and Anaplasma phagocytophilum. Evidence presented in
      this study indicates that the blood borne protozoans Babesia microti and
      Cytauxzoon felis are not widely distributed in stray cat populations in Milan,
      northern Italy, and that the significance of cats as a reservoir host for B.
      microti in this area is limited. 

PMID- 24895630
TI  - Integrative effects of feeding Aspergillus awamori and fructooligosaccharide on
      growth performance and digestibility in broilers: promotion muscle protein
      metabolism.
AB  - This study was conducted to show the effect of Aspergillus awamori (AA),
      fructooligosaccharide (FOS), and combined Aspergillus awamori and
      fructooligosaccharide (AA + FOS) on growth, digestibility, blood parameters, and
      expression of some growth-related genes. A total of 60 broiler chicks at the age
      of 15 d were divided into a control group (n = 15) and 3 treatment groups. The
      control group was fed a basal diet, and the treatment groups were fed basal diets
      supplemented with 0.05% AA, 0.05% FOS, and combined of 0.05% AA and 0.05% FOS.
      Results from measurement of growth performance and digestibility revealed a
      significant increase in the body weight gain with improved feed conversion rate
      in the experimental groups. Interestingly, dry matter digestibility (DMD) and
      crude protein utilization (CPU) were improved. In addition, plasma total
      cholesterol and low density lipoprotein-cholesterol (LDL-C) were decreased, while
      plasma high density lipoprotein-cholesterol (HDL-C) was increased by feeding AA,
      FOS, and AA + FOS. Expressions of growth hormone secretagogue receptor (GHSR),
      insulin-like growth factor 1 (IGF-1), and insulin-like growth factor 1 receptor
      (IGF1R) were increased in experimental groups. In conclusion, the supplementation
      of either Aspergillus awamori or fructooligosaccharide or both improves
      digestibility and growth performance probably by promoting skeletal muscle
      protein metabolism.

PMID- 24895631
TI  - Vitamin D receptor agonists: suitable candidates as novel therapeutic options in
      autoimmune inflammatory myopathy.
AB  - The primary aim in the treatment of autoimmune inflammatory myopathies (IMs) is
      to recover muscle function. The presence of immune/inflammatory cell infiltrates
      within muscle tissues represents the common feature of different IM subtypes,
      albeit a correlation between muscular damage extent and inflammation degree is
      often lacking. Treatments for IMs are based on life-long immunosuppressive
      therapy, with the well known adverse effects; recovery is incomplete for many
      patients. More effective therapies, with reduced side-effects, are highly
      desirable. Vitamin D receptor (VDR) agonists emerge to retain pleiotropic anti
      inflammatory properties, since they regulate innate and adaptive immunity by
      switching the immune response from proinflammatory T helper 1 (Th1) type to
      tolerogenic T helper 2 (Th2) type dominance. In skeletal muscle cells less
      hypercalcemic VDR ligands target powerful mediators of inflammation, such as TNF
      alpha and TNF alpha driven paths, without affecting immune or muscle cells
      viability, retaining the potentiality to counteract Th1 driven overreactivity
      established by the self-enhancing inflammatory loop between immune and skeletal
      muscle cells. This review summarizes those features of VDR agonists as candidates
      in future treatment of IM. 

PMID- 24895632
TI  - Biochemical and functional characterization of Parawixia bistriata spider venom
      with potential proteolytic and larvicidal activities.
AB  - Toxins purified from the venom of spiders have high potential to be studied
      pharmacologically and biochemically. These biomolecules may have biotechnological
      and therapeutic applications. This study aimed to evaluate the protein content of
      Parawixia bistriata venom and functionally characterize its proteins that have
      potential for biotechnological applications. The crude venom showed no
      phospholipase, hemorrhagic, or anti-Leishmania activities attesting to low
      genotoxicity and discrete antifungal activity for C. albicans. However the
      following activities were observed: anticoagulation, edema, myotoxicity and
      proteolysis on casein, azo-collagen, and fibrinogen. The chromatographic and
      electrophoretic profiles of the proteins revealed a predominance of acidic,
      neutral, and polar proteins, highlighting the presence of proteins with high
      molecular masses. Five fractions were collected using cation exchange
      chromatography, with the P4 fraction standing out as that of the highest purity.
      All fractions showed proteolytic activity. The crude venom and fractions P1, P2,
      and P3 showed larvicidal effects on A. aegypti. Fraction P4 showed the presence
      of a possible metalloprotease (60 kDa) that has high proteolytic activity on azo
      collagen and was inhibited by EDTA. The results presented in this study
      demonstrate the presence of proteins in the venom of P. bistriata with potential
      for biotechnological applications.

PMID- 24895633
TI  - Antidepressant-like effect of Ilex paraguariensis in rats.
AB  - In this study, we investigated the possible antidepressant-like effect of I.
      paraguariensis in rats. Rats were treated for four weeks with an aqueous extract
      of I. paraguariensis in drinking water, following the traditional preparation of
      this beverage. After the period of treatment, behavioral (elevated plus-maze,
      open field test, and forced swimming test) and biochemical parameters (lipid
      peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase
      activity) were evaluated. Animals were also analyzed on forced swimming test
      after 24 hours of I. paraguariensis intake. An additional group was injected with
      selegiline 24 hours and 30 minutes before forced swimming test as positive
      control. HPLC analysis revealed the profile of I. paraguariensis extract. I.
      paraguariensis reduced the immobility time on forced swimming test without
      significant changes in locomotor activity in the open field test. Any
      anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through
      the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis
      was not accompanied by inhibitory effect on monoamine oxidase activity. There
      were no significant alterations on lipid peroxidation, thiol content, and vitamin
      C levels among the groups. In conclusion, aqueous extract of I. paraguariensis
      decreases the time of immobility in rats suggesting an antidepressant-like
      effect. 

PMID- 24895634
TI  - Identification of virulence factors genes in Escherichia coli isolates from women
      with urinary tract infection in Mexico.
AB  - E coli isolates (108) from Mexican women, clinically diagnosed with urinary tract
      infection, were screened to identify virulence genes, phylogenetic groups, and
      antibiotic resistance. Isolates were identified by MicroScan4 system;
      additionally, the minimum inhibitory concentration (MIC) was assessed. The
      phylogenetic groups and 16 virulence genes encoding adhesins, toxins,
      siderophores, lipopolysaccharide (LPS), and invasins were identified by PCR.
      Phylogenetic groups distribution was as follows: B1 9.3%, A 30.6%, B2 55.6%, and
      D 4.6%. Virulence genes prevalence was ecp 98.1%, fimH 86.1%, traT 77.8%,
      sfa/focDE 74.1%, papC 62%, iutA 48.1%, fyuA 44.4%, focG 2.8%, sfaS 1.9%, hlyA
      7.4%, cnf-1 6.5%, cdt-B 0.9%, cvaC 2.8%, ibeA 2.8%, and rfc 0.9%. Regarding
      antimicrobial resistance it was above 50% to ampicillin/sulbactam, ampicillin,
      piperacillin, trimethoprim/sulfamethoxazole, ciprofloxacin, and levofloxacin.
      Uropathogenic E. coli clustered mainly in the pathogenic phylogenetic group B2.
      The isolates showed a high presence of siderophores and adhesion genes and a low
      presence of genes encoding toxins. The high frequency of papC gene suggests that
      these isolates have the ability to colonize the kidneys. High resistance to drugs
      considered as first choice treatment such as trimethoprim/sulfamethoxazole and
      fluoroquinolones was consistently observed. 

PMID- 24895635
TI  - Human serum albumin conjugates of 7-ethyl-10-hydroxycamptothecin (SN38) for
      cancer treatment.
AB  - SN38 (7-ethyl-10-hydroxy-comptothecin) is a potent metabolite of irinotecan,
      which has been approved for treatment of metastatic colorectal cancer.
      Considering the notable potency of SN38, it has been introduced as an anticancer
      candidate. In this study, human serum albumin (HSA) conjugates of SN38 were
      formulated to overcome the solubility problem beside improving the active form
      stability and tumor tissue targeting. In this target, two different molar ratios
      of conjugates (SN38 : HSA 15 : 1 and 60 : 1) were prepared by derivatization of
      20-hydroxyl group of SN38 with glycine, followed by addition of succinyl group to
      glycine through which HSA was covalently attached. The conjugates with particle
      size of about 100 nm revealed enhanced water solubility and were relatively
      stable in neutral and acidic solutions. For SN38-HSA-15 and SN38-HSA-60 IC50
      values were compared with irinotecan in HT-29 human colon cancer cells.
      Furthermore, biodistribution studies of SN38-HSA conjugate resulted in proper
      blood concentration level within 4 h. Moreover, blood cytotoxicity assay revealed
      no toxicity effect on liver and spleen. Collectively, our present investigation
      offers a water-soluble form of SN38 attached to HSA and suggests using favorable
      properties as a promising anticancer agent for further preclinical and clinical
      investigations.

PMID- 24895636
TI  - Frequency and clinical implication of the R450H mutation in the thyrotropin
      receptor gene in the Japanese population detected by Smart Amplification Process
      2.
AB  - In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H
      mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the
      frequency and clinical implication of the R450H mutation in TSHR in the general
      population of Japanese adults using smart amplification process 2 (SmartAmp2). We
      designed SmartAmp2 primer sets to detect this mutation using a drop of whole
      blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in
      429 Japanese participants who had not been found to have thyroid disease. Two
      cases without antithyroid antibodies were heterozygous for the R450H mutation in
      TSHR. Thus, the prevalence of this mutation was 0.47% in the general population
      and 0.63% among those without antithyroid antibodies. Their serum TSH
      concentrations were higher than the average TSH concentration not only in
      subjects without antithyroid antibodies but also in those with antithyroid
      antibodies. The R450H mutation in TSHR is relatively common in the Japanese
      population and potentially affects thyroid function. The present study
      demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in
      TSHR, which is one of the common causes of TSH resistance in the Japanese
      population. 

PMID- 24895637
TI  - Psychometric properties of the Greek Haem-A-QoL for measuring quality of life in
      Greek haemophilia patients.
AB  - BACKGROUND AND OBJECTIVES: Health Related Quality of Life (HRQoL) is an important
      health outcome measure in haemophilia. The aim of this study was to assess the
      psychometric properties of the Greek version of Haem-A-QoL, a disease-specific
      questionnaire for haemophiliacs. METHODS: Haem-A-QoL and SF-36 were administered
      to 118 adult haemophilia patients. Hypothesized scale structure, internal
      consistency (Cronbach's alpha ), and test-retest reliability, as well as various
      types of construct validity were evaluated. RESULTS: Scale structure of Haem-A
      QoL was confirmed, with good item convergence (87%) and discrimination (80.6%)
      rates. Cronbach's alpha was >0.70 for all but one dimension (dealing) and test
      retest reliability was significantly high. The strength of Spearman's
      correlations between Haem-A-QoL and SF-36 scales ranged from 0.25 to 0.75 (P <
      0.01). Multiple stepwise linear regression analysis revealed that all but one
      Haem-A-QoL dimensions were important predictors of SF-36 scales. Known-groups
      comparisons yielded consistent support of the instruments' construct validity and
      significant relationships were identified for age, educational level, haemophilia
      type, disease severity, and viral infections. CONCLUSION: Overall, the
      psychometric properties of the Greek version of Haem-A-QoL, resulting from this
      first time administration of the instrument to Greek adult haemophiliacs,
      confirmed it as a reliable and valid questionnaire for assessing haemophilia
      specific HRQoL in Greece.

PMID- 24895638
TI  - Association between follicular fluid leptin and serum insulin levels in
      nonoverweight women with polycystic ovary syndrome.
AB  - AIMS: We evaluated the links between leptin and visfatin levels and fertilization
      rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in
      vitro fertilization/embryo transfer (IVF). MATERIALS AND METHODOLOGY: We
      recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women
      (control-NOW). All women underwent IVF. Androgens, 17- beta -estradiol (17 beta 
      E2), and insulin levels were measured in plasma and/or serum and leptin and
      visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF
      visfatin). RESULTS: In NOW-PCOS, both serum and FF-leptin were significantly
      lower than in control-NOW. In NOW-PCOS, significant correlations were found
      between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in
      control-NOW, FF-leptin levels were not correlated with insulinemia. Serum
      visfatin levels were not significantly different in NOW-PCOS and control-NOW, but
      FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS
      than in control-NOW. CONCLUSIONS: Both serum leptin levels and FF-leptin are BMI-
      and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other
      reports showing that FF-leptin levels are predictive of fertilization rates,
      lower than normal FF-leptin levels in NOW-PCOS may explain their lower
      fertilization rate and this may be related to the level of insulin and/or insulin
      resistance.

PMID- 24895639
TI  - Bone marrow plasma cell assessment before peripheral blood stem cell mobilization
      in patients with multiple myeloma undergoing autologous stem cell
      transplantation.
AB  - The current definition of complete response (CR) in multiple myeloma (MM)
      includes negative serum and urine immunofixation (IFE) tests and <5% bone marrow
      plasma cells (BMPCs). However, many studies of the prognostic impact of
      pretransplant response have not included BMPCs. We evaluated the prognostic
      impact of BMPC assessment before peripheral blood stem cell (PBSC) mobilization
      on subsequent transplant outcomes. BMPCs were assessed by CD138, kappa, and
      lambda immunostaining in 106 patients. After a median followup of 24.5 months,
      patients with <5% BMPCs had a significantly better progression-free survival
      (PFS) compared to those with >= 5% BMPCs (P = 0.005). Patients with <5% BMPCs +
      serologic CR showed superior PFS compared to those with <5% BMPCs + serologic non
      CR (P = 0.050) or >= 5% BMPCs + serologic non-CR (P = 0.001). Interestingly, the
      prognostic impact of BMPCs was more apparent for patients who did not achieve a
      serologic CR (P = 0.042) compared to those with a serologic CR (P = 0.647). We
      concluded that IFE negativity and <5% BMPCs before PBSC mobilization were
      important factors to predict PFS in patients with MM undergoing ASCT.
      Particularly, a significant impact of <5% BMPCs was observed in patients who did
      not achieve IFE negativity.

PMID- 24895643
TI  - Analysis of resonance response performance of C-band antenna using parasitic
      element.
AB  - Analysis of the resonance response improvement of a planar C-band (4-8 GHz)
      antenna is proposed using parasitic element method. This parasitic element based
      method is validated for change in the active and parasitic antenna elements. A
      novel dual-band antenna for C-band application covering 5.7 GHz and 7.6 GHz is
      designed and fabricated. The antenna is composed of circular parasitic element
      with unequal microstrip lines at both sides and a rectangular partial ground
      plane. A fractional bandwidth of 13.5% has been achieved from 5.5 GHz to 6.3 GHz
      (WLAN band) for the lower band. The upper band covers from 7.1 GHz to 8 GHz with
      a fractional bandwidth of 12%. A gain of 6.4 dBi is achieved at the lower
      frequency and 4 dBi is achieved at the upper frequency. The VSWR of the antenna
      is less than 2 at the resonance frequency.

PMID- 24895640
TI  - Association between eNOS 4b/a polymorphism and the risk of diabetic retinopathy
      in type 2 diabetes mellitus: a meta-analysis.
AB  - Many studies have assessed the association between eNOS-4b/a polymorphism and the
      risk of diabetic retinopathy (DR) among type 2 diabetic subjects. However, the
      results are inconsistent. In order to derive a more precise estimation of the
      association, a meta-analysis was conducted. Fifteen studies with 3, 183 cases and
      3, 410 controls were enrolled by searching the databases of Pubmed, Embase, China
      National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database. Summary
      odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The main
      analysis indicated no significant association between eNOS-4b/a polymorphism and
      the risk of DR in overall population [allelic model: OR = 0.94 (0.79-1.11);
      additive model: OR = 0.91 (0.73-1.14); recessive model: OR = 1.01 (0.81-1.25);
      dominant model: OR = 0.91 (0.75-1.09)]. Subgroup analysis by ethnicity also
      indicated no significant association. In conclusion, the current meta-analysis
      did not observe any association between the polymorphism of eNOS 4b/a and the
      risk of DR among type 2 diabetic subjects. However, larger well-designed studies
      are required to confirm this finding. 

PMID- 24895641
TI  - JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer
      protein, improves hyperglycemia and dyslipidemia independent of suppression of
      food intake in diabetic rats.
AB  - We investigated the effects of JTT-130 on glucose and lipid metabolism
      independent of the suppression of feeding by comparing with pair-fed animals.
      Male Zucker diabetic fatty (ZDF) rats were divided into control, JTT-130
      treatment, and pair-fed groups. The rats were fed with a regular powdered diet
      with or without JTT-130 as a food admixture for 6 weeks. We compared the effects
      on glucose and lipid metabolism in JTT-130 treatment group with those in pair-fed
      group. RESULTS. Hyperglycemia in ZDF rats was prevented in both JTT-130 treatment
      and pair-fed groups, but the prevention in pair-fed group became poor with time.
      Moreover, reduction in plasma cholesterol levels was observed only in JTT-130
      treatment group. JTT-130 treatment group showed improved glucose tolerance at 5
      weeks after treatment and significant elevation of portal glucagon-like peptide-1
      (GLP-1) levels. The hepatic lipid content in JTT-130 treatment group was
      decreased as compared with pair-fed group. Furthermore, pancreatic protection
      effects, such as an increase in pancreatic weight and an elevation of insulin
      positive area in islets, were observed after JTT-130 treatment. CONCLUSIONS. JTT
      130 improves hyperglycemia and dyslipidemia via a mechanism independent of
      suppression of food intake, which is ascribed to an enhancement of GLP-1
      secretion and a reduction of lipotoxicity.

PMID- 24895642
TI  - Serum fibroblast growth factor 21 levels are correlated with the severity of
      diabetic retinopathy.
AB  - The aim of the study was to assess serum fibroblast growth factor 21 (FGF21)
      concentrations in Chinese type 2 diabetic patients with and without retinopathy
      and to assess the association between FGF21 and the severity of retinopathy. 117
      diabetic patients were compared with 68 healthy controls. Fasting blood glucose,
      serum total cholesterol, serum triglycerides, serum insulin, and serum FGF21
      levels were estimated. FGF21 concentrations in the patients were significantly
      higher than those in control. In the patient group there was a significant
      positive correlation between FGF21, insulin level, and homeostasis model
      assessment index. Serum FGF21 concentrations in patients with proliferative
      diabetic retinopathy or nonproliferative diabetic retinopathy were significantly
      higher than those in patients without diabetic retinopathy. When the presence of
      diabetes was defined as the final variable in the conditional logistic regression
      model with the FGF21 concentration as the continuous variable, FGF21 was
      significantly involved in the model. This study shows that the increase in serum
      concentration of FGF21 was associated with the severity of diabetic retinopathy
      and suggests that FGF21 may play a role in the pathogenesis of diabetic
      retinopathy and its degree. 

PMID- 24895644
TI  - Saliency detection using sparse and nonlinear feature representation.
AB  - An important aspect of visual saliency detection is how features that form an
      input image are represented. A popular theory supports sparse feature
      representation, an image being represented with a basis dictionary having sparse
      weighting coefficient. Another method uses a nonlinear combination of image
      features for representation. In our work, we combine the two methods and propose
      a scheme that takes advantage of both sparse and nonlinear feature
      representation. To this end, we use independent component analysis (ICA) and
      covariant matrices, respectively. To compute saliency, we use a biologically
      plausible center surround difference (CSD) mechanism. Our sparse features are
      adaptive in nature; the ICA basis function are learnt at every image
      representation, rather than being fixed. We show that Adaptive Sparse Features
      when used with a CSD mechanism yield better results compared to fixed sparse
      representations. We also show that covariant matrices consisting of nonlinear
      integration of color information alone are sufficient to efficiently estimate
      saliency from an image. The proposed dual representation scheme is then evaluated
      against human eye fixation prediction, response to psychological patterns, and
      salient object detection on well-known datasets. We conclude that having two
      forms of representation compliments one another and results in better saliency
      detection. 

PMID- 24895645
TI  - Effects of ADC nonlinearity on the spurious dynamic range performance of
      compressed sensing.
AB  - Analog-to-information converter (AIC) plays an important role in the compressed
      sensing system; it has the potential to significantly extend the capabilities of
      conventional analog-to-digital converter. This paper evaluates the impact of AIC
      nonlinearity on the dynamic performance in practical compressed sensing system,
      which included the nonlinearity introduced by quantization as well as the circuit
      non-ideality. It presents intuitive yet quantitative insights into the harmonics
      of quantization output of AIC, and the effect of other AIC nonlinearity on the
      spurious dynamic range (SFDR) performance is also analyzed. The analysis and
      simulation results demonstrated that, compared with conventional ADC-based
      system, the measurement process decorrelates the input signal and the
      quantization error and alleviate the effect of other decorrelates of AIC, which
      results in a dramatic increase in spurious free dynamic range (SFDR). 

PMID- 24895647
TI  - A simple approach for monitoring business service time variation.
AB  - Control charts are effective tools for signal detection in both manufacturing
      processes and service processes. Much of the data in service industries comes
      from processes having nonnormal or unknown distributions. The commonly used
      Shewhart variable control charts, which depend heavily on the normality
      assumption, are not appropriately used here. In this paper, we propose a new
      asymmetric EWMA variance chart (EWMA-AV chart) and an asymmetric EWMA mean chart
      (EWMA-AM chart) based on two simple statistics to monitor process variance and
      mean shifts simultaneously. Further, we explore the sampling properties of the
      new monitoring statistics and calculate the average run lengths when using both
      the EWMA-AV chart and the EWMA-AM chart. The performance of the EWMA-AV and EWMA
      AM charts and that of some existing variance and mean charts are compared. A
      numerical example involving nonnormal service times from the service system of a
      bank branch in Taiwan is used to illustrate the applications of the EWMA-AV and
      EWMA-AM charts and to compare them with the existing variance (or standard
      deviation) and mean charts. The proposed EWMA-AV chart and EWMA-AM charts show
      superior detection performance compared to the existing variance and mean charts.
      The EWMA-AV chart and EWMA-AM chart are thus recommended. 

PMID- 24895648
TI  - Average gait differential image based human recognition.
AB  - The difference between adjacent frames of human walking contains useful
      information for human gait identification. Based on the previous idea a
      silhouettes difference based human gait recognition method named as average gait
      differential image (AGDI) is proposed in this paper. The AGDI is generated by the
      accumulation of the silhouettes difference between adjacent frames. The advantage
      of this method lies in that as a feature image it can preserve both the kinetic
      and static information of walking. Comparing to gait energy image (GEI), AGDI is
      more fit to representation the variation of silhouettes during walking. Two
      dimensional principal component analysis (2DPCA) is used to extract features from
      the AGDI. Experiments on CASIA dataset show that AGDI has better identification
      and verification performance than GEI. Comparing to PCA, 2DPCA is a more
      efficient and less memory storage consumption feature extraction method in gait
      based recognition. 

PMID- 24895649
TI  - Low power adder based digital filter for QRS detector.
AB  - Most of the Biomedical applications use dedicated processors for the
      implementation of complex signal processing. Among them, sensor network is also a
      type, which has the constraint of low power consumption. Since the processing
      elements are the most copiously used operations in the signal processors, the
      power consumption of this has the major impact on the system level application.
      In this paper, we introduce low power concept of transistor stacking to reduce
      leakage power; and new architectures based on stacking to implement the full
      adder and its significance at the digital filter level for QRS detector are
      implemented. The proposed concept has lesser leakage power at the adder as well
      as filter level with trade-off in other quality metrics of the design. This
      enabled the design to be dealt with as the low-power corner and can be made
      adaptable to any level of hierarchical abstractions as per the requirement of the
      application. The proposed architectures are designed, modeled at RTL level using
      the Verilog-HDL, and synthesized in Synopsys Design Compiler by mapping the
      design to 65 nm technology library standard cells.

PMID- 24895646
TI  - Gossypol toxicity from cottonseed products.
AB  - Gossypol is a phenolic compound produced by pigment glands in cotton stems,
      leaves, seeds, and flower buds (Gossypium spp.). Cottonseed meal is a by-product
      of cotton that is used for animal feeding because it is rich in oil and proteins.
      However, gossypol toxicity limits cottonseed use in animal feed. High
      concentrations of free gossypol may be responsible for acute clinical signs of
      gossypol poisoning which include respiratory distress, impaired body weight gain,
      anorexia, weakness, apathy, and death after several days. However, the most
      common toxic effects is the impairment of male and female reproduction. Another
      important toxic effect of gossypol is its interference with immune function,
      reducing an animal's resistance to infections and impairing the efficiency of
      vaccines. Preventive procedures to limit gossypol toxicity involve treatment of
      the cottonseed product to reduce the concentration of free gossypol with the most
      common treatment being exposure to heat. However, free gossypol can be released
      from the bound form during digestion. Agronomic selection has produced cotton
      varieties devoid of glands producing gossypol, but these varieties are not
      normally grown because they are less productive and are more vulnerable to
      attacks by insects. 

PMID- 24895650
TI  - Comparative analysis of lycorine in wild plant and callus culture samples of
      Hymenocallis littoralis by HPLC-UV method.
AB  - The Hymenocallis littoralis, an ornamental and medicinal plant, had been
      traditionally used for wound healing. In the present study, an analytical method
      using HPLC with ultraviolet detection was developed for the quantification of
      lycorine in the extracts of different parts of wild plant and tissue culture
      samples of H. littoralis. The separation was achieved using a reversed-phase
      column. The method was found to be accurate, repeatable, and sensitive for the
      quantification of minute amount of lycorine present in the samples. The highest
      lycorine content was found in the bulb extract (2.54 +/- 0.02 MUg/mg) whereas the
      least was in the root extract (0.71 +/- 0.02 MUg/mg) of the wild plants. Few
      callus culture samples had high content of lycorine, comparable to that of wild
      plants. The results showed that plant growth regulators, 2,4
      dichlorophenoxyacetic acid (2,4-D) alone at 4.5 MUM (2.58 +/- 0.38 MUg/mg) or a
      combination of 2,4-D at 9.00 MUM with 4.5 MUM of 6-benzylaminopurine (BAP), were
      the optimum concentrations for the production of high lycorine (2.45 +/- 0.15
      MUg/mg) content in callus culture. The present analytical method could be of
      value for routine quantification of lycorine in the tissue culture production and
      standardization of the raw material or extracts of H. littoralis.

PMID- 24895651
TI  - Voltage-mode multifunction biquadratic filter with one input and six outputs
      using two ICCIIs.
AB  - A novel voltage-mode multifunction biquadratic filter with one input and six
      outputs is presented. The proposed circuit can realize inverting and noninverting
      low-pass, bandpass, and high-pass filters, simultaneously, by using two inverting
      second-generation current conveyors (ICCIIs), two grounded capacitors, and four
      resistors. Moreover, the proposed circuit offers the following attractive
      advantages: no requirements for component matching conditions, the use of only
      grounded capacitors, and low active and passive sensitivities. HSPICE and MATLAB
      simulations results are provided to demonstrate the theoretical analysis. 

PMID- 24895652
TI  - Subalgebras of BCK/BCI-algebras based on cubic soft sets.
AB  - Operations of cubic soft sets including "AND" operation and "OR" operation based
      on P-orders and R-orders are introduced and some related properties are
      investigated. An example is presented to show that the R-union of two internal
      cubic soft sets might not be internal. A sufficient condition is provided, which
      ensure that the R-union of two internal cubic soft sets is also internal.
      Moreover, some properties of cubic soft subalgebras of BCK/BCI-algebras based on
      a given parameter are discussed. 

PMID- 24895653
TI  - An unconditionally stable, positivity-preserving splitting scheme for nonlinear
      Black-Scholes equation with transaction costs.
AB  - This paper deals with the numerical analysis of nonlinear Black-Scholes equation
      with transaction costs. An unconditionally stable and monotone splitting method,
      ensuring positive numerical solution and avoiding unstable oscillations, is
      proposed. This numerical method is based on the LOD-Backward Euler method which
      allows us to solve the discrete equation explicitly. The numerical results for
      vanilla call option and for European butterfly spread are provided. It turns out
      that the proposed scheme is efficient and reliable. 

PMID- 24895654
TI  - Distributed optimal power and rate control in wireless sensor networks.
AB  - With the rapid development of wireless sensor networks, reducing energy
      consumption is becoming one of the important factors to extend node lifetime, and
      it is necessary to adjust the launching power of each node because of the limited
      energy available to the sensor nodes in the networks. This paper proposes a power
      and rate control model based on the network utility maximization (NUM) framework,
      where a weighting factor is used to reflect the influence degree of the sending
      power and transmission rate to the utility function. In real networks, nodes
      interfere with each other in the procedure of transmitting signal, which may lead
      to signal transmission failure and may negatively have impacts on networks
      throughput. Using dual decomposition techniques, the NUM problem is decomposed
      into two distributed subproblems, and then the conjugate gradient method is
      applied to solve the optimization problem with the calculation of the Hessian
      matrix and its inverse in order to guarantee fast convergence of the algorithm.
      The convergence proof is also provided in this paper. Numerical examples show
      that the proposed solution achieves significant throughput compared with exiting
      approaches. 

PMID- 24895655
TI  - Fixed point results for G-alpha-contractive maps with application to boundary
      value problems.
AB  - We unify the concepts of G-metric, metric-like, and b-metric to define new notion
      of generalized b-metric-like space and discuss its topological and structural
      properties. In addition, certain fixed point theorems for two classes of G-alpha 
      admissible contractive mappings in such spaces are obtained and some new fixed
      point results are derived in corresponding partially ordered space. Moreover,
      some examples and an application to the existence of a solution for the first
      order periodic boundary value problem are provided here to illustrate the
      usability of the obtained results.

PMID- 24895656
TI  - Inverted S-shaped compact antenna for X-band applications.
AB  - A novel probe-fed compact inverted S-shaped multifrequency patch antenna is
      designed. By employing two rectangular slots that change the conventional
      rectangular patch into an inverted S-shaped patch, the antenna is able to operate
      in triple frequency in the X-band. The performance criteria of the proposed
      design have been experimentally verified by fabricating a printed prototype. The
      measured results show that the -10 dB impedance bandwidth of the proposed antenna
      at lower band is 5.02% (8.69-9.14 GHz), at middle band is 9.13% (10.47-11.48
      GHz), and at upper band is 3.79% (11.53-11.98 GHz). Two elliptical slots are
      introduced in the ground plane to increase the peak gain. The antenna is excited
      by a simple probe feeding mechanism. The overall antenna dimension is  0.52lambda
      * 0.60lambda * 0.046lambda at a lower resonance frequency of 9.08 GHz. The
      antenna configuration and parametric investigation are conducted with the help of
      the high frequency structural simulator, and a good agreement is achieved between
      the simulated and measured data. The stable gain, omnidirectional radiation
      pattern, and consistent radiation efficiency in the achieved operating band make
      the proposed antenna a suitable candidate for X-band applications.

PMID- 24895657
TI  - Results from ad hoc and routinely collected data among celiac women with
      infertility or pregnancy related disorders: Italy, 2001-2011.
AB  - Celiac disease (CD) is a chronic autoimmune illness triggered by gluten
      consumption in genetically predisposed individuals. Worldwide, CD prevalence is
      approximately 1%. Several studies suggest a higher prevalence of undiagnosed CD
      in patients with infertility. We described reproductive disorders and assessed
      the frequency of hospital admissions for infertility among celiac women aged 15
      49. We conducted two surveys enrolling a convenient sample of celiac women,
      residing in Apulia or in Basilicata (Italy). Moreover, we selected hospital
      discharge records (HDRs) of celiac women and women with an exemption for CD, and
      matched the lists with HDRs for reproductive disorders. In the surveys we
      included 91 celiac women; 61.5% of them reported menstrual cycle disorders. 47/91
      reported at least one pregnancy and 70.2% of them reported problems during
      pregnancy. From the HDRs and the registry of exemption, we selected 4,070 women
      with CD; the proportion of women hospitalized for infertility was higher among
      celiac women than among resident women in childbearing age (1.2% versus 0.2%).
      Our findings highlight a higher prevalence of reproductive disorders among celiac
      women than in the general population suggesting that clinicians might consider
      testing for CD women presenting with pregnancy disorders or infertility. 

PMID- 24895658
TI  - The effect of malrotation of tibial component of total knee arthroplasty on
      tibial insert during high flexion using a finite element analysis.
AB  - One of the most common errors of total knee arthroplasty procedure is a
      malrotation of tibial component. The stress on tibial insert is closely related
      to polyethylene failure. The objective of this study is to analyze the effect of
      malrotation of tibial component for the stress on tibial insert during high
      flexion using a finite element analysis. We used Stryker NRG PS for analysis.
      Three different initial conditions of tibial component including normal, 15
      degrees  internal malrotation, and 15 degrees  external malrotation were
      analyzed. The tibial insert made from ultra-high-molecular-weight polyethylene
      was assumed to be elastic-plastic while femoral and tibial metal components were
      assumed to be rigid. Four nonlinear springs attached to tibial component
      represented soft tissues around the knee. Vertical load was applied to femoral
      component which rotated from 0 degrees  to 135 degrees  while horizontal load
      along the anterior posterior axis was applied to tibial component during flexion.
      Maximum equivalent stresses on the surface were analyzed. Internal malrotation
      caused the highest stress which arose up to 160% of normal position. External
      malrotation also caused higher stress. Implanting prosthesis in correct position
      is important for reducing the risk of abnormal wear and failure. 

PMID- 24895659
TI  - Waiting endurance time estimation of electric two-wheelers at signalized
      intersections.
AB  - The paper proposed a model for estimating waiting endurance times of electric two
      wheelers at signalized intersections using survival analysis method. Waiting
      duration times were collected by video cameras and they were assigned as censored
      and uncensored data to distinguish between normal crossing and red-light running
      behavior. A Cox proportional hazard model was introduced, and variables revealing
      personal characteristics and traffic conditions were defined as covariates to
      describe the effects of internal and external factors. Empirical results show
      that riders do not want to wait too long to cross intersections. As signal
      waiting time increases, electric two-wheelers get impatient and violate the
      traffic signal. There are 12.8% of electric two-wheelers with negligible wait
      time. 25.0% of electric two-wheelers are generally nonrisk takers who can obey
      the traffic rules after waiting for 100 seconds. Half of electric two-wheelers
      cannot endure 49.0 seconds or longer at red-light phase. Red phase time, motor
      vehicle volume, and conformity behavior have important effects on riders' waiting
      times. Waiting endurance times would decrease with the longer red-phase time, the
      lower traffic volume, or the bigger number of other riders who run against the
      red light. The proposed model may be applicable in the design, management and
      control of signalized intersections in other developing cities. 

PMID- 24895660
TI  - Effects of NAA and BAP, double-layered media, and light distance on in vitro
      regeneration of Nelumbo nucifera Gaertn. (lotus), an aquatic edible plant.
AB  - In vitro direct regeneration of Nelumbo nucifera Gaertn. was successfully
      achieved from immature explants (yellow plumule) cultured on a solid MS media
      supplemented with combinations of 0.5 mg/L BAP and 1.5 mg/L NAA which resulted in
      16.00 +/- 0.30 number of shoots per explant and exhibited a new characteristic of
      layered multiple shoots, while normal roots formed on the solid MS basal media.
      The double-layered media gave the highest number of shoots per explant with a
      ratio of 2 : 1 (liquid to solid) with a mean number of 16.67 +/- 0.23 shoots per
      explant with the formation of primary and secondary roots from immature explants.
      In the study involving light distance, the tallest shoot (16.67 +/- 0.23 mm)
      obtained from the immature explants was at a light distance of 200 mm from the
      source of inflorescent light (1000 lux). The plantlets were successfully
      acclimatized in clay loam soil after 8 months being maintained under in vitro
      conditions.

PMID- 24895661
TI  - Phototunable magnetism in copper octacyanomolybdate.
AB  - We introduce copper molybdenum cyanides of general formula Cu2[Mo(CN)8] . nH2O,
      which can serve as optofunctional magnetic devices. Their ground states generally
      stay paramagnetic down to temperatures of the K order but exhibit a spontaneous
      magnetization upon photoirradiation usually below a few tens of K. To interest us
      still further, such a ferromagnetic stateinduced by blue-laser irradiation is
      demagnetized step by step through further application of red or near-infrared
      laser pulses. We solve this intriguing photomagnetism. The ground-state
      properties are fully revealed by means of a group-theoretical technique. Taking
      account of experimental observations, we simulate applying pump laser pulses to a
      likely ground state and successfully reproduce both the magnetization and
      demagnetization dynamics. We monitor the photorelaxation process through angle
      resolved photoemission spectroscopy. Electrons are fully itinerant in any of the
      photoinduced steady states, forming a striking contrast to the initial
      equilibrium state of atomic aspect. The fully demagnetized final steady state
      looks completely different from the initial paramagnetism but bears good analogy
      to one of the possible ground states available with the Coulomb repulsion on Cu
      sites suppressed.

PMID- 24895662
TI  - Fixed point theorems for generalized alpha -beta-weakly contraction mappings in
      metric spaces and applications.
AB  - We extend the notion of generalized weakly contraction mappings due to Choudhury
      et al. (2011) to generalized alpha-beta-weakly contraction mappings. We show with
      examples that our new class of mappings is a real generalization of several known
      classes of mappings. We also establish fixed point results for such mappings in
      metric spaces. Applying our new results, we obtain fixed point results on
      ordinary metric spaces, metric spaces endowed with an arbitrary binary relation,
      and metric spaces endowed with graph. 

PMID- 24895663
TI  - A multiobjective interval programming model for wind-hydrothermal power system
      dispatching using 2-step optimization algorithm.
AB  - Wind-hydrothermal power system dispatching has received intensive attention in
      recent years because it can help develop various reasonable plans to schedule the
      power generation efficiency. But future data such as wind power output and power
      load would not be accurately predicted and the nonlinear nature involved in the
      complex multiobjective scheduling model; therefore, to achieve accurate solution
      to such complex problem is a very difficult task. This paper presents an interval
      programming model with 2-step optimization algorithm to solve multiobjective
      dispatching. Initially, we represented the future data into interval numbers and
      simplified the object function to a linear programming problem to search the
      feasible and preliminary solutions to construct the Pareto set. Then the
      simulated annealing method was used to search the optimal solution of initial
      model. Thorough experimental results suggest that the proposed method performed
      reasonably well in terms of both operating efficiency and precision. 

PMID- 24895664
TI  - Solar tracking error analysis of Fresnel reflector.
AB  - Depending on the rotational structure of Fresnel reflector, the rotation angle of
      the mirror was deduced under the eccentric condition. By analyzing the influence
      of the sun tracking rotation angle error caused by main factors, the change rule
      and extent of the influence were revealed. It is concluded that the tracking
      errors caused by the difference between the rotation axis and true north
      meridian, at noon, were maximum under certain conditions and reduced at morning
      and afternoon gradually. The tracking error caused by other deviations such as
      rotating eccentric, latitude, and solar altitude was positive at morning,
      negative at afternoon, and zero at a certain moment of noon. 

PMID- 24895665
TI  - Multivariate time series similarity searching.
AB  - Multivariate time series (MTS) datasets are very common in various financial,
      multimedia, and hydrological fields. In this paper, a dimension-combination
      method is proposed to search similar sequences for MTS. Firstly, the similarity
      of single-dimension series is calculated; then the overall similarity of the MTS
      is obtained by synthesizing each of the single-dimension similarity based on
      weighted BORDA voting method. The dimension-combination method could use the
      existing similarity searching method. Several experiments, which used the
      classification accuracy as a measure, were performed on six datasets from the UCI
      KDD Archive to validate the method. The results show the advantage of the
      approach compared to the traditional similarity measures, such as Euclidean
      distance (ED), cynamic time warping (DTW), point distribution (PD), PCA
      similarity factor (SPCA), and extended Frobenius norm (Eros), for MTS datasets in
      some ways. Our experiments also demonstrate that no measure can fit all datasets,
      and the proposed measure is a choice for similarity searches.

PMID- 24895666
TI  - Crude oil price forecasting based on hybridizing wavelet multiple linear
      regression model, particle swarm optimization techniques, and principal component
      analysis.
AB  - Crude oil prices do play significant role in the global economy and are a key
      input into option pricing formulas, portfolio allocation, and risk measurement.
      In this paper, a hybrid model integrating wavelet and multiple linear regressions
      (MLR) is proposed for crude oil price forecasting. In this model, Mallat wavelet
      transform is first selected to decompose an original time series into several
      subseries with different scale. Then, the principal component analysis (PCA) is
      used in processing subseries data in MLR for crude oil price forecasting. The
      particle swarm optimization (PSO) is used to adopt the optimal parameters of the
      MLR model. To assess the effectiveness of this model, daily crude oil market,
      West Texas Intermediate (WTI), has been used as the case study. Time series
      prediction capability performance of the WMLR model is compared with the MLR,
      ARIMA, and GARCH models using various statistics measures. The experimental
      results show that the proposed model outperforms the individual models in
      forecasting of the crude oil prices series. 

PMID- 24895668
TI  - Optimal location through distributed algorithm to avoid energy hole in mobile
      sink WSNs.
AB  - In multihop data collection sensor network, nodes near the sink need to relay on
      remote data and, thus, have much faster energy dissipation rate and suffer from
      premature death. This phenomenon causes energy hole near the sink, seriously
      damaging the network performance. In this paper, we first compute energy
      consumption of each node when sink is set at any point in the network through
      theoretical analysis; then we propose an online distributed algorithm, which can
      adjust sink position based on the actual energy consumption of each node
      adaptively to get the actual maximum lifetime. Theoretical analysis and
      experimental results show that the proposed algorithms significantly improve the
      lifetime of wireless sensor network. It lowers the network residual energy by
      more than 30% when it is dead. Moreover, the cost for moving the sink is
      relatively smaller. 

PMID- 24895667
TI  - A qualitative study exploring facilitators for improved health behaviors and
      health behavior programs: mental health service users' perspectives.
AB  - OBJECTIVE: Mental health service users experience high rates of cardiometabolic
      disorders and have a 20-25% shorter life expectancy than the general population
      from such disorders. Clinician-led health behavior programs have shown moderate
      improvements, for mental health service users, in managing aspects of
      cardiometabolic disorders. This study sought to potentially enhance health
      initiatives by exploring (1) facilitators that help mental health service users
      engage in better health behaviors and (2) the types of health programs mental
      health service users want to develop. METHODS: A qualitative study utilizing
      focus groups was conducted with 37 mental health service users attending a
      psychosocial rehabilitation center, in Northern British Columbia, Canada.
      RESULTS: Four major facilitator themes were identified: (1) factors of
      empowerment, self-value, and personal growth; (2) the need for social support;
      (3) pragmatic aspects of motivation and planning; and (4) access. Participants
      believed that engaging with programs of physical activity, nutrition, creativity,
      and illness support would motivate them to live more healthily. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: Being able to contribute to health behavior programs,
      feeling valued and able to experience personal growth are vital factors to engage
      mental health service users in health programs. Clinicians and health care policy
      makers need to account for these considerations to improve success of health
      improvement initiatives for this population.

PMID- 24895669
TI  - Novel hexagonal dual-mode substrate integrated waveguide filter with source-load
      coupling.
AB  - Hexagonal dual-mode cavity and its application to substrate integrated waveguide
      (SIW) filter are presented. The hexagonal SIW resonator which can combine
      flexibility of rectangular cavity and performance of circular cavity is
      convenient for dual-mode bandpass filters design. By introducing coupling between
      source and load, the filter not only has good selectivity due to two controllable
      transmission zeros, but also has a small size by the virtue of its single-cavity
      structure. A demonstration filter with a center frequency of 10 GHz and a 3 dB
      fractional bandwidth of 4% is designed and fabricated to validate the proposed
      structure. Measured results are in good agreement with simulated ones.

PMID- 24895671
TI  - Effect of fast freeze-thaw cycles on mechanical properties of ordinary-air
      entrained concrete.
AB  - Freezing-thawing resistance is a very significant characteristic for concrete in
      severe environment (such as cold region with the lowest temperature below 0
      degrees C). In this study, ordinary-air-entrained (O-A-E) concrete was produced
      in a laboratory environment; the compressive strength, cubic compressive strength
      of C50, C40, C30, C25, and C20 ordinary-air-entrained concrete, tensile strength,
      and cleavage strength of C30 ordinary-air-entrained concrete were measured after
      fast freeze-thaw cycles. The effects of fast freeze-thaw cycles on the mechanical
      properties (compressive strength and cleavage strength) of ordinary-air-entrained
      concrete materials are investigated on the basis of the experimental results. And
      the concise mathematical formula between mechanical behavior and number of fast
      freeze-thaw cycles was established. The experiment results can be used as a
      reference in design, maintenance, and life prediction of ordinary-air-entrained
      concrete structure (such as dam, offshore platform, etc.) in cold regions. 

PMID- 24895672
TI  - Integrated project scheduling and staff assignment with controllable processing
      times.
AB  - This paper addresses a decision problem related to simultaneously scheduling the
      tasks in a project and assigning the staff to these tasks, taking into account
      that a task can be performed only by employees with certain skills, and that the
      length of each task depends on the number of employees assigned. This type of
      problems usually appears in service companies, where both tasks scheduling and
      staff assignment are closely related. An integer programming model for the
      problem is proposed, together with some extensions to cope with different
      situations. Additionally, the advantages of the controllable processing times
      approach are compared with the fixed processing times. Due to the complexity of
      the integrated model, a simple GRASP algorithm is implemented in order to obtain
      good, approximate solutions in short computation times. 

PMID- 24895673
TI  - 1-Quasiconformal mappings and CR mappings on Goursat groups.
AB  - We show that 1-quasiconformal mappings on Goursat groups are CR or anti-CR
      mappings. This can reduce the determination of 1-quasiconformal mappings to the
      determination of CR automorphisms of CR manifolds, which is a fundamental problem
      in the theory of several complex variables. 

PMID- 24895670
TI  - Caenorhabditis elegans as model system in pharmacology and toxicology: effects of
      flavonoids on redox-sensitive signalling pathways and ageing.
AB  - Flavonoids are secondary plant compounds that mediate diverse biological
      activities, for example, by scavenging free radicals and modulating intracellular
      signalling pathways. It has been shown in various studies that distinct flavonoid
      compounds enhance stress resistance and even prolong the life span of organisms.
      In the last years the model organism C. elegans has gained increasing importance
      in pharmacological and toxicological sciences due to the availability of various
      genetically modified nematode strains, the simplicity of modulating genes by
      RNAi, and the relatively short life span. Several studies have been performed
      demonstrating that secondary plant compounds influence ageing, stress resistance,
      and distinct signalling pathways in the nematode. Here we present an overview of
      the modulating effects of different flavonoids on oxidative stress, redox
      sensitive signalling pathways, and life span in C. elegans introducing the
      usability of this model system for pharmacological and toxicological research. 

PMID- 24895674
TI  - Recent advances on bioinspired computation.

PMID- 24895675
TI  - New proofs of some q-summation and q-transformation formulas.
AB  - We obtain an expectation formula and give the probabilistic proofs of some
      summation and transformation formulas of q-series based on our expectation
      formula. Although these formulas in themselves are not the probability results,
      the proofs given are based on probabilistic concepts. 

PMID- 24895677
TI  - A comparative study of electric load curve changes in an urban low-voltage
      substation in Spain during the economic crisis (2008-2013).
AB  - This paper presents a comparative study of the electricity consumption (EC) in an
      urban low-voltage substation before and during the economic crisis (2008-2013).
      This low-voltage substation supplies electric power to near 400 users. The EC was
      measured for an 11-year period (2002-2012) with a sampling time of 1 minute. The
      study described in the paper consists of detecting the changes produced in the
      load curves of this substation along the time due to changes in the behaviour of
      consumers. The EC was compared using representative curves per time period
      (precrisis and crisis). These representative curves were obtained after a
      computational process, which was based on a search for days with similar curves
      to the curve of a determined (base) date. This similitude was assessed by the
      proximity on the calendar, day of the week, daylight time, and outdoor
      temperature. The last selection parameter was the error between the nearest
      neighbour curves and the base date curve. The obtained representative curves were
      linearized to determine changes in their structure (maximum and minimum
      consumption values, duration of the daily time slot, etc.). The results primarily
      indicate an increase in the EC in the night slot during the summer months in the
      crisis period.

PMID- 24895679
TI  - A heuristic for disassembly planning in remanufacturing system.
AB  - This study aims to improve the efficiency of disassembly planning in
      remanufacturing environment. Even though disassembly processes are considered as
      the reverse of the corresponding assembly processes, under some technological and
      management constraints the feasible and efficient disassembly planning can be
      achieved by only well-designed algorithms. In this paper, we propose a heuristic
      for disassembly planning with the existence of disassembled part/subassembly
      demands. A mathematical model is formulated for solving this problem to determine
      the sequence and quantity of disassembly operations to minimize the disassembly
      costs under sequence-dependent setup and capacity constraints. The disassembly
      costs consist of the setup cost, part inventory holding cost, disassembly
      processing cost, and purchasing cost that resulted from unsatisfied demand. A
      simple but efficient heuristic algorithm is proposed to improve the quality of
      solution and computational efficiency. The main idea of heuristic is to divide
      the planning horizon into the smaller planning windows and improve the
      computational efficiency without much loss of solution quality. Performances of
      the heuristic are investigated through the computational experiments. 

PMID- 24895678
TI  - Mineral element contents in commercially valuable fish species in Spain.
AB  - The aim of this study was to measure selected metal concentrations in Trachurus
      trachurus, Trachurus picturatus, and Trachurus mediterraneus, which are widely
      consumed in Spain. Principal component analysis suggested that the variable Cr
      was the main responsible variable for the identification of T. trachurus, the
      variables As and Sn for T. mediterraneus, and the rest of variables for T.
      picturatus. This well-defined discrimination between fish species provided by
      mineral element allows us to distinguish them on the basis of their metal
      content. Based on the samples collected, and recognizing the inferential
      limitation of the sample size of this study, the metal concentrations found are
      below the proposed limit values for human consumption. However, it should be
      taken into consideration that there are other dietary sources of these metals. In
      conclusion, metal contents in the fish species analyzed are acceptable for human
      consumption from a nutritional and toxicity point of view. 

PMID- 24895676
TI  - Effect of preventive hormonal therapy on breast density: a systematic qualitative
      review.
AB  - Breast density (BD) is recognized as one of the strongest independent risk
      factors of breast cancer (BC). Unlike most other risk factors, BD can be
      modified, suggesting that it may be a biomarker for preventive interventions. We
      conducted a qualitative systematic review to address the effect of preventive
      hormonal therapy on BD. Among the 26 relevant studies, 10 assessed the effect of
      tamoxifen on BD (TAM: n = 2,877), 9 that of raloxifene (RLX: n = 1,544), and 7
      that of aromatase inhibitors (AI: n = 416). The studies were characterized by a
      large heterogeneity in designs and in methods of BD measurement. BD could be
      reduced by TAM (10 studies/10). However, the effect of RLX and AI on BD remains
      unclear due to conflicting results between studies. Consequently, it is crucial
      to develop practical, accurate, and reproducible methods of measurement in order
      to be able to compare the effect of preventive hormonal agents on BD and to
      determine whether change in BD can be used as a predictor of response to therapy.

PMID- 24895680
TI  - Effect of different arbuscular mycorrhizal fungi on growth and physiology of
      maize at ambient and low temperature regimes.
AB  - The effect of four different arbuscular mycorrhizal fungi (AMF) on the growth and
      lipid peroxidation, soluble sugar, proline contents, and antioxidant enzymes
      activities of Zea mays L. was studied in pot culture subjected to two temperature
      regimes. Maize plants were grown in pots filled with a mixture of sandy and black
      soil for 5 weeks, and then half of the plants were exposed to low temperature for
      1 week while the rest of the plants were grown under ambient temperature and
      severed as control. Different AMF resulted in different root colonization and low
      temperature significantly decreased AM colonization. Low temperature remarkably
      decreased plant height and total dry weight but increased root dry weight and
      root-shoot ratio. The AM plants had higher proline content compared with the non
      AM plants. The maize plants inoculated with Glomus etunicatum and G. intraradices
      had higher malondialdehyde and soluble sugar contents under low temperature
      condition. The activities of catalase (CAT) and peroxidase of AM inoculated maize
      were higher than those of non-AM ones. Low temperature noticeably decreased the
      activities of CAT. The results suggest that low temperature adversely affects
      maize physiology and AM symbiosis can improve maize seedlings tolerance to low
      temperature stress. 

PMID- 24895681
TI  - Chinese unknown word recognition for PCFG-LA parsing.
AB  - This paper investigates the recognition of unknown words in Chinese parsing. Two
      methods are proposed to handle this problem. One is the modification of a
      character-based model. We model the emission probability of an unknown word using
      the first and last characters in the word. It aims to reduce the POS tag
      ambiguities of unknown words to improve the parsing performance. In addition, a
      novel method, using graph-based semisupervised learning (SSL), is proposed to
      improve the syntax parsing of unknown words. Its goal is to discover additional
      lexical knowledge from a large amount of unlabeled data to help the syntax
      parsing. The method is mainly to propagate lexical emission probabilities to
      unknown words by building the similarity graphs over the words of labeled and
      unlabeled data. The derived distributions are incorporated into the parsing
      process. The proposed methods are effective in dealing with the unknown words to
      improve the parsing. Empirical results for Penn Chinese Treebank and TCT Treebank
      revealed its effectiveness. 

PMID- 24895682
TI  - Ultrastructure of plant leaf cuticles in relation to sample preparation as
      observed by transmission electron microscopy.
AB  - The leaf cuticular ultrastructure of some plant species has been examined by
      transmission electron microscopy (TEM) in only few studies. Attending to the
      different cuticle layers and inner structure, plant cuticles have been grouped
      into six general morphological types. With the aim of critically examining the
      effect of cuticle isolation and preparation for TEM analysis on cuticular
      ultrastructure, adaxial leaf cuticles of blue-gum eucalypt, grey poplar, and
      European pear were assessed, following a membrane science approach. The embedding
      and staining protocols affected the ultrastructure of the cuticles analysed. The
      solubility parameter, surface tension, and contact angles with water of pure
      Spurr's and LR-White resins were within a similar range. Differences were however
      estimated for resin : solvent mixtures, since Spurr's resin is combined with
      acetone and LR-White resin is mixed with ethanol. Given the composite hydrophilic
      and lipophilic nature of plant cuticles, the particular TEM tissue embedding and
      staining procedures employed may affect sample ultrastructure and the
      interpretation of the results in physicochemical and biological terms. It is
      concluded that tissue preparation procedures may be optimised to facilitate the
      observation of the micro- and nanostructure of cuticular layers and components
      with different degrees of polarity and hydrophobicity.

PMID- 24895683
TI  - The asymptotic solutions for a class of nonlinear singular perturbed differential
      systems with time delays.
AB  - We study a kind of vector singular perturbed delay-differential equations. By
      using the methods of boundary function and fractional steps, we construct the
      formula of asymptotic expansion and confirm the interior layer at t = sigma.
      Meanwhile, on the basis of functional analysis skill, the existence of the smooth
      solution and the uniform validity of the asymptotic expansion are proved. 

PMID- 24895684
TI  - Release behavior and toxicity profiles towards leukemia (WEHI-3B) cell lines of 6
      mercaptopurine-PEG-coated magnetite nanoparticles delivery system.
AB  - The coating of an active drug, 6-mercaptopurine, into the iron oxide
      nanoparticles-polyethylene glycol (FNPs-PEG) in order to form a new
      nanocomposite, FPEGMP-2, was accomplished using coprecipitation technique. The
      resulting nanosized with a narrow size distribution magnetic polymeric particles
      show the superparamagnetic properties with 38.6 emu/g saturation magnetization at
      room temperature. Fourier transform infrared spectroscopy and the thermal
      analysis study supported the formation of the nanocomposite and the enhancement
      of thermal stability in the resulting nanocomposite comparing with its
      counterpart in free state. The loading of 6-mercaptopurine (MP) in the FPEGMP-2
      nanocomposite was estimated to be about 5.6% and the kinetic experimental data
      properly correlated with the pseudo-second order model. Also, the release of MP
      from the FPEGMP-2 nanocomposite shows the sustained release manner which is
      remarkably lower in phosphate buffered solution at pH 7.4 than pH 4.8, due to
      different release mechanism. The maximum percentage release of MP from the
      nanocomposite reached about 60% and 97% within about 92 and 74 hours when exposed
      to pH 7.4 and 4.8, respectively.

PMID- 24895686
TI  - Modeling and simulation of network-on-chip systems with DEVS and DEUS.
AB  - Networks on-chip (NoCs) provide enhanced performance, scalability, modularity,
      and design productivity as compared with previous communication architectures for
      VLSI systems on-chip (SoCs), such as buses and dedicated signal wires. Since the
      NoC design space is very large and high dimensional, evaluation methodologies
      rely heavily on analytical modeling and simulation. Unfortunately, there is no
      standard modeling framework. In this paper we illustrate how to design and
      evaluate NoCs by integrating the Discrete Event System Specification (DEVS)
      modeling framework and the simulation environment called DEUS. The advantage of
      such an approach is that both DEVS and DEUS support modularity-the former being a
      sound and complete modeling framework and the latter being an open, general
      purpose platform, characterized by a steep learning curve and the possibility to
      simulate any system at any level of detail. 

PMID- 24895685
TI  - Enzymatic activity analysis and catalytic essential residues identification of
      Brucella abortus malate dehydrogenase.
AB  - Malate dehydrogenase (MDH) plays important metabolic roles in bacteria. In this
      study, the recombinant MDH protein (His-MDH) of Brucella abortus was purified and
      its ability to catalyze the conversion of oxaloacetate (OAA) to L-malate (hereon
      referred to as MDH activity) was analyzed. Michaelis Constant (Km) and Maximum
      Reaction Velocity (Vmax) of the reaction were determined to be 6.45 * 10(-3) M
      and 0.87 mM L(-1)min(-1), respectively. In vitro studies showed that His-MDH
      exhibited maximal MDH activity in pH 6.0 reaction buffer at 40 degrees C. The
      enzymatic activity was 100%, 60%, and 40% inhibited by Cu(2+), Zn(2+), and
      Pb(2+), respectively. In addition, six amino acids in the MDH were mutated to
      investigate their roles in the enzymatic activity. The results showed that the
      substitutions of amino acids Arg 89, Asp 149, Arg 152, His 176, or Thr 231 almost
      abolished the activity of His-MDH. The present study will help to understand
      MDH's roles in B. abortus metabolism.

PMID- 24895687
TI  - Nanomechanical spectroscopy of synthetic and biological membranes.
AB  - We report that atomic force microscopy based high-speed nanomechanical analysis
      can identify components of complex heterogeneous synthetic and biological
      membranes from the measured spectrum of nanomechanical properties. We have
      investigated phase separated ternary lipid bilayers and purple membranes of
      Halobacterium salinarum. The nanomechanical spectra recorded on these samples
      identify all membrane components, some of which are difficult to resolve in
      conventional phase images. This non-destructive approach can aid the design of
      synthetic lipid bilayers and studies lateral organization of complex
      heterogeneous cellular membranes. 

PMID- 24895688
TI  - Highly efficient Mo2C nanotubes as a counter electrode catalyst for organic redox
      shuttles in dye-sensitized solar cells.
AB  - Molybdenum carbide nanotubes (Mo2C-NTs) were synthesized and showed remarkable
      catalytic activity for regeneration of an organic sulfide redox shuttle. The dye
      sensitized solar cells (DSCs) using Mo2C-NTs as the counter electrode (CE) showed
      a high power conversion efficiency of 6.22%, which is much higher than the DSCs
      using a conventional Pt CE (3.91%). 

PMID- 24895689
TI  - Galectin 9 and PINCH, novel immunotherapy targets of renal cell carcinoma: a
      rationale to find potential tumour antigens and the resulting cytotoxic T
      lymphocytes induced by the derived peptides.
AB  - OBJECTIVE: To analyse and then generalize the mechanism by which partial or
      complete response is achieved among a limited number of patients with metastatic
      renal cell carcinoma (RCC) treated with interferon or interleukin-2. MATERIALS
      AND METHODS: An expression library of RCC (clear-cell carcinoma) was screened
      using the sera of patients with metastatic RCC who benefited from partial or
      complete response to cytokine therapy, the postulation being that those
      remarkable responders obtained specific cellular immunity against RCC with the
      antibodies to react with the cancer antigen. Peripheral blood mononuclear-cells
      (PBMCs) from healthy volunteers were stimulated with the antigen-derived peptides
      to induce specific cytotoxic T lymphocytes (CTLs). Specific activities of CTLs
      were measured by 51Cr-releasing assay. RESULTS: Among 15 positive clones
      isolated, two novel genes, galectin 9 and PINCH, were expressed at much higher
      levels in cancerous lesions than in normal tissues in all the patients with clear
      cell carcinoma who were examined. Both HLA-A*2402-restricted and HLA-A*0201
      restricted CTLs were induced by each antigen-derived peptide to exhibit specific
      and highly cytotoxic activities towards RCC cells. Specific CTLs were induced
      abundantly, as shown by flow cytometry analysis of the CTLs labelled with
      fluorescein isothiocyanate anti-CD107a and APC anti-CD8. The clonal expansion of
      the CTLs was shown by the clonality of T-cell receptor Vbeta repertoires.
      CONCLUSION: A novel approach based on clinical observations yielded promising
      tumour antigens as immunotherapy targets of RCC.

PMID- 24895690
TI  - Ripples for her. Interview with Dr Lowina Tse Hei-yee and Dr Mona Lam.

PMID- 24895691
TI  - Portable ECG machine.

PMID- 24895692
TI  - A 21-year-old female with galactorrhea.

PMID- 24895693
TI  - A 58 year-old male with hallucinations and ataxia.

PMID- 24895694
TI  - A 46 year-old woman with a spinal cord mass.

PMID- 24895695
TI  - A 56-year old man with thalamic and frontal masses.

PMID- 24895696
TI  - Antioxidant status in patients with psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease with an unknown aetiology that
      has been associated with abnormal plasma lipid metabolism and oxidative stress.
      There are controversial results in the previous studies investigating
      oxidant/antioxidant systems in psoriasis.The aim of this work was to evaluate the
      plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase
      (CAT), total bilirubin (T. Bili), direct bilirubin (D. Bili), uric acid (UA),
      apolipoproteins (ApoA1 and ApoB), Lp(a) and activities of paraxonase 1 (PON1) in
      100 patients with psoriasis and 100 controls, and to look for a correlation
      between these parameters in psoriasis.PON1, bilirubin and UA were measured
      spectrophotometrically, MDA by the high-performance liquid chromatography method,
      apolipoproteins and Lp(a) by immunoprecipitation assays, and lipid and other
      biochemical parameters were determined by routine laboratory methods.In patients
      with psoriasis, there was a significant decrease in PON1, SOD and CAT activities
      (P < 0.05) and an increase in MDA levels (P < 0.01). Also, the levels of
      bilirubin (total and direct) and UA were decreased in patients with psoriasis but
      were not significant (P > 0.05).These results suggest that psoriasis was in a
      state of oxidative stress and that the protective effects of high-density
      lipoprotein against atherosclerosis may be dependent on PON1 activity. Moreover,
      there is a negative correlation between antioxidant with Lp(a), apoB and MDA
      levels, suggesting that subjects with higher levels of Lp(a) and apoB and lower
      levels of antioxidant are more exposed to oxidative damage. These findings may
      explain in part the reported increase in cardiovascular mortality in psoriasis.

PMID- 24895697
TI  - Stable neutral double hydrophilic block copolymer capillary coating for capillary
      electrophoretic separations.
AB  - Quaternized diblock copolymer, poly(N-methyl-2-vinylpyridinium iodide-block
      ethylene oxide), was successfully used as a neutral, dynamic coating to suppress
      the electroosmotic flow. The block copolymer consisted of two polymers that were
      linked covalently together. The cationic block (poly(N-methyl-2-vinylpyridinium
      iodide)) was bound efficiently to the negatively charged capillary wall via
      electrostatic interactions, and the hydrophilic block (ethylene oxide) stabilized
      the system and created a neutral capillary surface with ultralow electroosmotic
      flow (+2.0 +/- 4.5 * 10(-10) m(2)/Vs). The main advantages of the coating were
      simple and fast preparation, easy regeneration and automation, and stable
      electroosmotic flow. To emphasize the potential of this type of coating its
      stability was measured at a wide pH range demonstrating a high stability in the
      pH range of 4.0-10.5 and lifetime up to 8 days. The successful studies carried
      out with beta-blockers, basic proteins, and lipoproteins proved the suitability
      of the coating for the separation of different sized analytes. Furthermore, the
      neutral coating developed is useful in a wide range of protein analysis and
      biological interaction studies under physiological condition.

PMID- 24895699
TI  - Cytomegalovirus-associated hemophagocytic lymphohistiocytosis in  a patient with
      myasthenia gravis treated with azathioprine.

PMID- 24895700
TI  - Cloaked in a starry sky.

PMID- 24895701
TI  - [Critically examining the symptoms and diagnoses that are taken for granted in
      family medicine. Creating an own school].

PMID- 24895702
TI  - [Study of infectious diseases in a primary care clinic with a majority immigrant
      population. Application of microbiological techniques in the primary care
      clinic].
AB  - INTRODUCTION: Patients are often seen in Primary Care due to infectious diseases.
      The aetiology of these diseases is often unclear. The application of basic
      microbiological techniques in the Primary Care clinic could improve the diagnosis
      and patient management. The purpose of this study is to introduce basic
      techniques and rapid diagnostics in the management of patients attending a
      Primary Care clinic. METHODS: The analysis of patient samples by microbiological
      stains or rapid tests. RESULTS: In the study of 249 samples analysed on patients
      in the clinic, an aetiological diagnosis of the infection was made in 23% of the
      cases. A microbiology result that helped in the treatment was obtained in 72% of
      the patients. CONCLUSION: The application of basic microbiological techniques may
      improve diagnosis and therefore the management of patients visiting the Primary
      Care clinic. The characteristics of the population served (mostly immigrant, low
      socio-economic level, difficulty in monitoring patients) suggest that this
      project could be very useful in that kind of population. It would require larger
      studies to assess the application on a larger scale and cost-effectiveness of
      these measures

PMID- 24895698
TI  - Neurological events related to influenza A (H1N1) pdm09.
AB  - OBJECTIVES: To review neurological complications after the influenza A (H1N1)
      pdm09, highlighting the clinical differences between patients with post-vaccine
      or viral infection. DESIGN: A search on Medline, Ovid, EMBASE, and PubMed
      databases using the keywords "neurological complications of Influenza AH1N1" or
      "post-vaccine Influenza AH1N1." SETTING: Only papers written in English, Spanish,
      German, French, Portuguese, and Italian published from March 2009 to December
      2012 were included. SAMPLE: We included 104 articles presenting a total of 1636
      patient cases. In addition, two cases of influenza vaccine-related neurological
      events from our neurological care center, arising during the period of study,
      were also included. MAIN OUTCOME MEASURES: Demographic data and clinical
      diagnosis of neurological complications and outcomes: death, neurological
      sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection.
      RESULTS: The retrieved cases were divided into two groups: the postvaccination
      group, with 287 patients, and the viral infection group, with 1349 patients. Most
      patients in the first group were adults. The main neurological complications were
      Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All
      patients survived. Pediatric patients were predominant in the viral infection
      group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent
      sequelae. A wide spectrum of neurological complications was observed.
      CONCLUSIONS: Fatal cases and severe, permanent, neurological sequelae were
      observed in the infection group only. Clinical outcome was more favorable in the
      post-vaccination group. In this context, the relevance of an accurate
      neurological evaluation is demonstrated for all suspicious cases, as well as the
      need of an appropriate long-term clinical and imaging follow-up of infection and
      post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate
      the magnitude of neurological complications leading to permanent disability.

PMID- 24895703
TI  - [New model of professional self-management in primary care].
AB  - OBJECTIVE: To analyse the benefits of a new organisational model in Primary Care
      based on the empowerment of professional management compared to standard model
      (team led by medical director). To improve the quality of care, and patient and
      professional satisfaction. MATERIAL AND METHODS: In February 2009 six family
      physician (FP) and four administrative staff met to create a self-management
      group to care for the 10,281 population assigned to them. The total catchment
      population of the Primary Care (PC) centre was 32,318. Additionally, between
      March and December 2010 three FP, seven nurses and two administrative staff, were
      included in the self-management group making the total population served by the
      self-management group of 16,368, compared to 15,950 patients seen using the
      standard model. The model gave priority to self-demand management, professional
      self-coverage, to reduce clinic bureaucracy, greater efficiency and participation
      in research and teaching. RESULTS: 1) Milestone in Pilot Phase (December-2008 to
      December-2009): increase in attended population, reduction in clinic visits,
      significant reduction in delay to be visited by a doctor; significant reduction
      of complementary tests (x-rays, laboratory tests); increase in use of generic
      drugs and reduction of expensive and new drugs without added value, and active
      participation in teaching and clinical trials. 2) Consolidation Phase (December
      2010, compared to other professionals working in a standard model in the same
      centre): self-management group reported a lower percentage of clinic visits and a
      higher percentage of visits resolved through telephoning the clinic. Furthermore,
      the self-management group achieved better financial results than the control
      group (additional medical tests, pharmacy budget). The self-management group had
      improved job satisfaction compared to control group (measured by Professional
      Questionnaire QoL-35). CONCLUSIONS: The new model has increased professional
      satisfaction and may improve results in some health indicators (accessibility,
      efficiency, pharmacy budget) compared with the usual clinical practice.

PMID- 24895704
TI  - [Prevalence of domestic violence in a primary care area of Santa Cruz de
      Tenerife].
AB  - OBJECTIVES: To estimate the prevalence of domestic violence (DV) in adult women
      attending Primary Care medical consultations, to determine the associated
      factors, and family physician involvement in its detection. MATERIAL AND METHODS:
      We performed a cross-sectional analytical study in two urban health districts of
      Santa Cruz de Tenerife, Canary Islands. A consecutive sample of women aged 18 or
      older, whether or not they had a current partner were selected.. The Bradley
      questionnaire, which is validated (26 items) and assesses physical, psychological
      and sexual violence was used anonymously. Demographic characteristics, and those
      related to the couple, health history, presence of anxiety and depression
      (Goldberg scale) were recorded. RESULTS: A total of 299 women were interviewed,
      and 154 women recognised some kind of abuse at least once in their life (51.5%,
      95% Cl: 40%-62%). Psychological violence was the most mentioned (n = 153;
      99.35%), followed by physical (n = 39; 25.32%) and sexual violence was stated by
      12 women (7.79%). Domestic violence was associated with: younger age, less time
      in a previous relationship, lack of social support (OR=2.18, P=.019), presence of
      probable anxiety (OR = 1.77, P = .015) and probable depression (OR = 1.58, P =
      .049). After multivariate analysis the association persisted with the Length of
      time of the relationship with previous partner (OR = 0.998; P < .0001) and the
      presence of probable anxiety (OR = 1.79; P = .024). Early detection of domestic
      violence was recorded in the medical records of 111 women (37.1%; 95% CI: 36.90
      37.23). CONCLUSIONS: As in other studies, DV is associated with mental disorders,
      and there is a need for greater involvement by family physicians to detect this
      prevalent problem in our clinics.

PMID- 24895705
TI  - [Update on the use of oral contraceptives in the treatment of endometriosis].
AB  - Endometriosis has a prevalence of about 10% and benefits from hormonal
      contraceptive treatment. It is a chronic and recurrent illness that occurs in
      fertile women, and is characterised by ectopic endometrial tissue. Clinical
      manifestations are: infertility, pain and pelvic mass. The goals of the treatment
      are: relief of symptoms, prevention of progression of disease and the stimulation
      of fertility. Current treatment options are: Expectant management, analgesia,
      hormonal therapy, surgery and combined therapies. The use of combined
      contraceptives is associated with a reduced risk of developing endometriosis,
      they are also a good choice to prevent pregnancy, and for women with minimal or
      mild symptoms. Progestins are used for symptomatic endometriosis and as an
      adjuvant to surgery. The combined contraceptives and the progestins must be
      considered as a first line treatment.

PMID- 24895706
TI  - [Rhabdomyolysis associated with cocaine use].
AB  - Cocaine is a drug that has been used by humans for 15 centuries. In our
      environment, the prevalence of alcohol consumption, and emergencies arising from
      it, has increased over the last 10 years. Cocaine has been used by 2.6% of the
      Spanish population between 15 and 64 years old at some time in their life,
      placing it among the most widely consumed illicit drug after cannabis. Cocaine
      use is associated with multiple complications: neurological, cardiovascular,
      psychiatry, nephrology, pulmonary and gastrointestinal. The first cases of
      rhabdomyolysis and kidney failure were found in the medical literature in 1987.
      Rhabdomyolysis is a potentially lethal clinical syndrome that results from the
      necrosis of muscle fibres, with the passage of its components into the
      circulation, and is underdiagnosed in primary care.

PMID- 24895707
TI  - ["Dizziness" as the first manifestation of a chronic progressive multiple
      sclerosis].
AB  - Dizziness is a common consultation in primary care. Most cases of dizziness can
      be managed in the first level of care. The family physician should be able to
      discriminate the cases that require referral to a second level, those potentially
      serious, and those requiring immediate care. We report the case of a patient with
      long-term dizziness and the diagnosis, clinical course, treatment and prognosis.

PMID- 24895708
TI  - [Tumour of the right lung vertex that produced a Pancoast syndrome: description
      of a case].
AB  - We describe a clinical case of an 80 year-old woman, with a history of
      Alzheimer's disease, who presented with right shoulder pain, numbness and
      decreased strength in the right arm, with right eye ptosis, cough and dysphagia.
      The chest X-Ray and thoracic-abdominal computed tomography scan showed a large
      mass in the upper lobe and apex of the right lung, supraclavicular metastatic
      lymph nodes. In the fine needle aspiration biopsy: poorly differentiated non
      small cell carcinoma. She was referred to Oncology to start chemotherapy
      treatment.

PMID- 24895709
TI  - [Merkel cell carcinoma in primary care].
AB  - Merkel cell tumour is a rare malignant cutaneous neoplasm of neuroendocrine
      origin. It mainly affects women over 50, is generally located in photo-exposed
      areas, is normally asymptomatic and of rapid growth. It has a high percentage of
      recurrences and metastasis, with the most frequent sites of dissemination being
      the skin, followed by the regional lymph nodes. Its treatment is still
      controversial. We report a clinical case of a 76-year-old woman with erythematous
      nodule in the right forearm that was not responding to treatment. The final
      diagnosis was a Merkel tumour and after the treatment it shows good progress.

PMID- 24895710
TI  - [Lyme disease. Is it so uncommon?].
AB  - Lyme disease, caused by Borrelia burgdorferi sensu lato, is a multisystem disease
      that may occur with rheumatic, dermatological, neurological symptoms and heart
      diseases. Its most typical lesion is erythema migrans, although not always
      present. The clinical diagnosis is supported by serology, and treatment is almost
      always tetracycline in young people and adults. Amoxicillin is most often used in
      children and pregnant women, and cephalosporins in the presence of neurological
      signs. The prognosis, with the appropriate treatment, is good. But if not treated
      promptly, there may be chronic signs, particularly, neurological, which may be
      disabling. In Spain, where the incidence is low, antimicrobial prophylaxis is
      indicated the after a tick bite.

PMID- 24895711
TI  - [An uncommon cause of persistent cough].
AB  - Chronic cough is defined as one that lasts more than three weeks. It is quite a
      usual reason for consultation in Primary Care. There is no consensus regarding
      the best strategy to diagnose it. The empirical treatment, additional tests, or
      both of them, are used to confirm the diagnosis. Furthermore, cough may have
      different causes as its origin can be in many Locations. In some cases, it may be
      hard to find the cause. In this article, an unusual case of persistent cough is
      presented, which turned out to be due to an aneurysm of the ascending aorta.

PMID- 24895712
TI  - [Rapid diagnosis units or immediate health care clinics in internal medicine.
      Analysis of the first six months of operation in Palencia (Spain)].
AB  - The extraordinary development experienced by Primary Care and medical specialties
      has not always been matched by better organisation of the health system. Waiting
      lists, the proportion of inappropriate stays and admissions, or absence of real
      mechanisms that enable to discriminate the severe cases from the banal in
      patients on the waiting list are situations that illustrate the above. Thus, the
      need arises to promote continuity of care between the two levels of care (Primary
      and Hospital) and improve patient care, most especially for those suspected of
      serious illness. In this context, Rapid Diagnostic Units were introduced;
      designed to improve coordination with Primary Care, and reduce delays especially
      in severe cases. In this paper, we review these units, and present our experience
      during the first six months of operation.

PMID- 24895713
TI  - [Jimson weed psychosis and public authorities].

PMID- 24895714
TI  - [Oesophagitis due to varicella zoster virus in a young immunocompetent male].

PMID- 24895715
TI  - [Beware of temporary tattoos!].

PMID- 24895716
TI  - [Let us move forward: together for a scientific and participative SEMERGEN].

PMID- 24895717
TI  - [Effectiveness of a social-physical activity intervention program in an elderly
      social risk population].
AB  - INTRODUCTION: The objective is to assess the effectiveness of a social-physical
      activity intervention program in the improvement of the health-related quality of
      life and functional physical condition of patients older than 65 years at social
      risk. MATERIAL AND METHODS: Quasi-experimental intervention (pretest-posttest).
      SETTING: Community activity; primary care and public education centres.
      PARTICIPANTS: Twenty-nine patients older than 65 years, seen at the health
      centre, with a diagnosis of social risk. The program included monthly health
      education sessions and two weekly sessions of one hour of exercise for 6 months.
      Measurements were taken before and at the end of the study. Outcome variables
      were: quality of life valued using the SF36 questionnaire and functional fitness
      through Senior Fitness Battery Test. RESULTS: After intervention improved all
      tests for the physical qualities improved after the intervention; in the 6
      minutes walk all subjects improved from baseline, with an average increase of 62
      +/- 36 metres (95% CI: 48-76). The SF-36 questionnaire improved 8 scales and
      mental summary component with a further increase of 6 points (P < .05).
      CONCLUSIONS: Social-physical activity intervention program improved the health
      related quality of life related and functional physical condition in older people
      at social risk. This paper provides evidence in favour of the implementation of
      social-physical community activities, coordinated between health services and
      education centres, aimed at the elderly at risk.

PMID- 24895718
TI  - [Impact of an on-line course on the level of knowledge of the OMI-AP program for
      primary care doctors].
AB  - OBJECTIVE: To evaluate the impact of an online course on the level of knowledge
      of the OMI-AP (Computerised Medical Office in Primary Care) program in medical
      personnel. MATERIAL AND METHODS: Improvement cycle to optimize the knowledge and
      use of OMI-AP by family physicians in the Murcia Health Service. A total of 55
      family physicians who completed an on-line course on OMI-AP were included.
      Advanced level training on the OMI-AP was given over a 2 month period via 9
      modules. The measurements made were performed in two phases: 1st) A questionnaire
      on the level of knowledge of OMI-AP (10 questions) was completed one week before
      the students enrolled in the course. 2nd) The same questionnaire was used one
      week after completing the course. RESULTS: The average score of the questionnaire
      was 5.31 points before the completion of the course and 7.70 points after the
      completion of the course (P < 05). In 9 of the 10 questions analysed the
      percentage of correct answers significantly improved after the completion of the
      course. CONCLUSIONS: The delivery of the on-line OMI-AP course for doctors has
      led to a significant improvement in the level of knowledge of the program,
      essential for the daily practice of family physicians in our health service. On
      line training greatly facilitates the training of professionals by enabling time
      management according to student needs.

PMID- 24895719
TI  - [Quality of care of patients with chronic heart failure in primary care].
AB  - INTRODUCTION: The prevalence of Chronic Heart Failure (CHF) in Spain is very
      high. It is the main cause of many hospital admissions and it is associated with
      high mortality rates. Its management in Primary Care is not always adequate. Our
      objective was to evaluate whether an educational intervention in general
      practitioners would improve the health care of their patients with chronic heart
      failure. MATERIAL AND METHODS: Prospective, randomised, and controlled study. A
      structured formative course was given to the intervention group (IG) of
      practitioners. A year later changes were compared with a control group (CG). The
      settings were two Primary Care Centres. One of them was in a rural setting, and
      the other one with a mixture of rural and urban populations. The study included
      185 patients diagnosed with CHF, with a mean age of 79.8 years, and they were
      assigned to 20 practitioners (Total population: 15, 921) We evaluated the quality
      of medical history, clinical examination, laboratory tests and treatment.
      RESULTS: At the end of the study there were marked differences between both
      groups. In the IG, the Medical History improved 1.42 points (95% CI: 0.57 to
      2.28), P = .001. The Clinical Examination improved 2.37 points (95% CI: 1.10 to
      3.65), P > .001 and the Laboratory Tests, 0.75 points (95% CI: -0.15 to 1.66), P
      = .10; The Overall Difference was 5.44 points (95% Cl: 3.25 to 7.62), P > .001.
      There were slight improvements in Treatment. CONCLUSIONS: The intervention
      promoted from our own work settings achieved a general improvement in the care of
      patients with heart failure.

PMID- 24895720
TI  - [An update on vaccines. Theory, realities and myths (I)].
AB  - Vaccines are biological products used to achieve active artificial immunization.
      Nowadays, vaccines are increasingly powerful, effective and safe. The list of
      vaccine-preventable diseases is expanding, which together with the increasing
      population likely to be vaccinated, it is expected that vaccine products will
      increase this century. This article is a brief but practical overview of the
      concept and types of vaccines, advances that have taken place recent decades on
      the fundamentals of the immune response and vaccine components (including the
      role of adjuvants). These concepts give rise to the criteria for when and how to
      vaccinate, to whom and why not to do it. With the hope that this text is useful,
      it ends with a brief overview as to why there are people who refuse vaccinations.

PMID- 24895721
TI  - [Legg-Calve-Perthes disease. Updated review].
AB  - Legg-Calve-Perthes disease affects the development of the child's hip. Although
      we know that is produced by aseptic necrosis of the femoral head, the cause of
      such necrosis is really unknown. Conventional radiology does not permit an early
      diagnosis; for this reason more advanced diagnostic techniques are needed. The
      timing of the diagnosis determines the degree of impact in the hip and has
      importance for the type of treatment to be applied, and the possible
      complications that the patient may develop. The aim of this work is to make the
      general practitioner aware of this disease and to take it into consideration when
      examining a child with problems related to the hip, and in order to make a
      correct differential diagnosis with conditions that have similar symptoms,
      because the final outcome will depend on how quickly the diagnosis was
      established and also the treatment.

PMID- 24895723
TI  - [Zuska disease. Diagnosis and treatment in primary care].
AB  - A fistula is an abnormal pathological communication which links two organs
      together or with the exterior. They are fibrous paths internally coated with
      granulation tissue, extending from an internal o primary opening to one or more
      openings located outside or on the skin. The recurrent mastitis that some
      patients suffer is due to a fistula between a lactiferous duct and the limit of
      the areola, and this condition is called a recurrent periareolar fistula.To
      incorporate this clinical condition into the proposed terminology, Zuska disease,
      is essential to believe in its existence, in order to to treat it from the
      source. The knowledge of this disease, a proper diagnosis and treatment will
      prevent the constant recurrence of mastitis as presented by these patients,
      avoiding their pilgrimage to various specialists. In this article we review this
      disease, methods of diagnosis and treatment.

PMID- 24895722
TI  - [Ventricular septal defect in an adult patient].
AB  - We report the case of a 46 year old asymptomatic male whose chest X-ray showed a
      right aortic knob and in the physical examination he had a systolic murmur with a
      palpable left parasternal heave. On performing the transesophageal
      echocardiography and MRI a ventricular septal defect (VSD) was observed which
      only requires periodic echocardiographic reviews. VSD is the most common
      congenital heart disease. The VSD may be membranous, inlet, trabecular, or
      infundibular. The clinical signs may range from only anodyne with a left
      pansystolic parasternal murmur on physical examination, up to lung hyper-flow
      which may lead to heart failure. The chest X-ray showed cardiomegaly, the
      electrocardiogram showed biventricular hypertrophy, and the echocardiography and
      MRI showed the size and number of communications. Treatment is conservative,
      since 50% close spontaneously in the first years of life, reserving surgery for
      symptomatic and asymptomatic cases with a significant shunt.

PMID- 24895724
TI  - [Pulmonary Langerhans cell histiocytosis: report of a case].
AB  - Pulmonary Langerhans cell histiocytosis is a rare disease of young adults,
      usually smokers, which is associated with significant morbidity. The course of
      the disease is unpredictable, ranging from benign self-limiting types with
      spontaneous regression, to malignant forms with progression to respiratory
      failure and death. Its cause is unknown, but most authors believe that there is
      an alteration in immune system regulation in these patients. We report a case of
      a patient with the diagnosis of pulmonary Langerhans cell histiocytosis and
      review the clinical characteristics, diagnosis and treatment of this disease. We
      consider this case of interest due by the low frequency of this disease.

PMID- 24895725
TI  - [Asthenia or anaemia. What is the diagnosis?].
AB  - Giardiasis is one of the most frequent parasitic infections in the world that
      must be considered in every patient with persistent diarrhoea or digestive tract
      and/or malabsorption symptoms after a foreign trip or in the immigrant
      population, although its presentation is not always the typical. A 25 year old
      woman from Equatorial Guinea was seen at the clinic due to several months of
      asthenia. The Laboratory analyses showed normocytic and normochromic anaemia and
      high erythrocyte sedimentation rate (ESR). Throughout the presentation of the
      case report the differential diagnoses of asthenia, normocytic and normochromic
      anemia and high ESR will be discussed until the final diagnosis of giardiasis was
      made.

PMID- 24895726
TI  - [Depression and panic attack in acne treated with isotretinoin].
AB  - Isotretinoin is a drug often used in adolescents with severe acne. Several side
      effects of this substance, including mental disorders, have been reported. We
      report the case of a 17 years old patient who was diagnosed with moderate
      depressive episode and panic attacks in relation to the use of this product. Due
      to the low frequency of psychiatric adverse reactions, the prescription of
      isotretinoin in adolescents is clearly justified. But patients and relatives
      should always be properly informed, with frequent re-assessments on whether to
      continue with treatment. The primary care physician must take into account the
      influence, sometimes not detected by other specialists, of many drugs at the
      onset of psychiatric symptoms, such as anxiety or depression.

PMID- 24895728
TI  - [Is influenza vaccination the new Bellerophon? The flu vaccine in primary care].

PMID- 24895729
TI  - [Carcinoid tumour: a case presentation].

PMID- 24895727
TI  - [Allergies in occupational health. Prevention aspects].
AB  - The concern in all countries of occupational health has led to the study of
      occupational risk factors and their impact on health. But maintaining the health
      of workers is increasingly complex, especially in occupational allergic diseases,
      which have increased in parallel with the increased use in industries of
      potentially irritating chemicals or allergens, leading to skin or respiratory
      sensitization. Diseases arising from these immunological substances are
      classified by Spanish Legislation as occupational diseases, as set out in Royal
      Decree 1299/2006, of November 10, 2006 (Group 1, Group 4 and Group 5). The most
      important ones in occupational medicine are allergic respiratory diseases and
      dermatological allergic diseases, although there are other allergies of interest,
      such as those involving mucous membranes (allergic eye diseases). A joint
      collaboration between the different medical disciplines involved to improve
      prevention at work is highly desirable.

PMID- 24895730
TI  - [Use of the Tzanck test for confirming the diagnosis of cutaneous herpes].

PMID- 24895731
TI  - Milnacipran influences the indexes of I-metaiodobenzylguanidine scintigraphy in
      elderly depressed patients.
AB  - AIM: This study investigated whether or not and how much milnacipran influences
      the indexes of I-metaiodobenzylguanidine (I-MIBG) scintigraphy, early heart-to
      mediastinum (H/M) ratio, delayed H/M ratio, and wash-out rate. METHODS: Six
      elderly depressed patients participated in the study. All six patients met the
      diagnostic criteria for a major depressive disorder. They were taking milnacipran
      for their depression. They needed differential diagnosis for Lewy body diseases
      due to their symptomatology. I-MIBG scintigraphy was performed twice for each
      subject, once under prescription of milnacipran and the other without
      prescription of milnacipran. RESULTS: Both early and delayed phase H/M ratio were
      significantly lower when taking milnacipran (early phase H/M ratio, P < 0.01,
      Cohen's d 1.62; delayed phase H/M ratio, P < 0.005, Cohen's d 1.98) than when not
      taking the drug. Wash-out rate (%) was significantly higher when taking
      milnacipran (P < 0.05, Cohen's d 2.31) than when off the drug. CONCLUSION: Taking
      milnacipran substantially influences the indexes of I-MIBG scintigraphy,
      indicating that taking the drug possibly causes a false-positive result for Lewy
      body diseases diagnosis.

PMID- 24895733
TI  - Sex-specific effects of subjective memory complaints with respect to cognitive
      impairment or depressive symptoms.
AB  - AIM: The aim of this study was to investigate the association between subjective
      memory complaints (SMC) and sex. METHODS: We researched the prevalence of SMC in
      a sample of 394 participants who were at least 60 years of age (138 male and 256
      female). We also administered the Mini-Mental State Examination (MMSE) and the
      Center for Epidemiologic Studies for Depression (CES-D) scale. A multiple
      logistic regression analysis, which included SMC in association with the MMSE or
      CES-D scores and other confounding factors, was performed to determine the
      influence of sex on SMC. A P-value < 0.05 was considered statistically
      significant. RESULTS: The durations of education of male participants were
      significantly higher than those of female participants. MMSE scores for female
      participants were significantly higher than those for male participants. There
      was no significant difference in CES-D scores between male and female
      participants. Twenty-four male participants and 72 female participants showed
      evidence of SMC. The incidence of SMC was more frequent in female participants
      than in male participants. In all participants, sex difference and CES-D score
      were significantly associated with SMC. In male participants, MMSE score was
      independently and significantly associated with SMC. Both in female participants
      and all participants, CES-D score was independently and significantly associated
      with SMC. CONCLUSION: SMC varied by sex and were associated with the degree of
      cognitive impairment in male participants, while they were associated with
      depressive symptoms in female participants.

PMID- 24895734
TI  - Mental disorders that exacerbated due to the Fukushima disaster, a complex
      radioactive contamination disaster.
AB  - AIM: The Fukushima disaster was caused by an earthquake that occurred on 11 March
      2011. Following the serious damage caused by the earthquake and the subsequent
      tsunami, radioactive contamination occurred because of the meltdown accident at
      the Fukushima nuclear power plant. We investigated what mental disorders were
      likely to become exacerbated under these conditions. METHODS: We surveyed
      psychiatric outpatients at Fukushima Medical University Hospital for 1 month (31
      days) from the day of the earthquake (March-April 2011). RESULTS: The survey
      revealed that bipolar I disorder was most likely to become exacerbated under the
      conditions and that the exacerbation exhibited was more likely to involve manic
      switches than depression. CONCLUSION: On the basis of the results of our study,
      particular care must be taken to follow up bipolar I disorder patients after a
      natural disaster. Our results also suggested the possible origin of bipolar I
      disorder.

PMID- 24895735
TI  - Psychosocial functioning is correlated with activation in the anterior cingulate
      cortex and left lateral prefrontal cortex during a verbal fluency task in
      euthymic bipolar disorder: a preliminary fMRI study.
AB  - AIM: Cognitive impairment may account for functional and occupational disability
      in patients with bipolar disorder even during periods of euthymia. While imaging
      suggests structural, neurochemical, and functional abnormalities in bipolar
      disorder patients, the pathophysiology of these deficits has not been elucidated.
      It was hypothesized that euthymic bipolar patients would have different cortical
      activation during a verbal fluency task compared to healthy controls, and that
      psychosocial functioning would be associated with prefrontal cortical activation
      during the task in the bipolar group. METHODS: Ten euthymic bipolar patients and
      10 healthy control participants (matched for age, gender, and years of education)
      underwent functional magnetic resonance imaging (fMRI) during a verbal fluency
      task, tapping task and visual task. Correlational analysis between the fMRI brain
      activation and clinical variables of the participants, including Global
      Assessment of Functioning (GAF) score, was performed. RESULTS: Compared to the
      controls, euthymic bipolar patients had significantly greater activation in the
      bilateral precuneus with similar behavioral performance during the verbal fluency
      task. There were no significant differences between the groups for the visual
      task or the simple motor task. Activation in both the left anterior cingulate
      cortex (ACC) and the left dorsolateral prefrontal cortex (PFC) were significantly
      positively correlated with GAF score in the euthymic bipolar patients.
      CONCLUSION: Both the ACC and lateral PFC regions are components of a neural
      network that plays a critical role in psychosocial functioning, and are often
      found to be affected in bipolar patients.

PMID- 24895736
TI  - [Being a physician. . . and forensic pathologist].

PMID- 24895732
TI  - TRP channels in lower  urinary tract dysfunction.
AB  - Lower urinary tract dysfunction (LUTd) represents a major healthcare problem.
      Although it is mostly not lethal, associated social disturbance, medical costs,
      loss of productivity and especially diminished quality of life should not be
      underestimated. Although more than 15% of people suffer from a form of LUTd to
      some extent, pathophysiology often remains obscure. In the past 20 years,
      transient receptor potential (TRP) channels have become increasingly important in
      this field of research. These intriguing ion channels are believed to be the main
      molecular sensors that generate bladder sensation. Therefore, they are intensely
      pursued as new drug targets for both curative and symptomatic treatment of
      different forms of LUTd. TRPV1 was the first of its class to be investigated.
      Actually, even before this channel was cloned, it had already been targeted in
      the bladder, with clinical trials of intravesical capsaicin instillations.
      Several other polymodally gated TRP channels, particularly TRPM8, TRPA1 and
      TRPV4, also appear to play a prominent role in bladder (patho)physiology. With
      this review, we provide a brief overview of current knowledge on the role of
      these TRP channels in LUTd and their potential as molecular targets for
      treatment.

PMID- 24895738
TI  - [In memory of a friend doctor].

PMID- 24895737
TI  - Activation and inhibition of transient receptor potential TRPM3-induced gene
      transcription.
AB  - BACKGROUND AND PURPOSE: Transient receptor potential-3 (TRPM3) channels function
      as Ca2+ permeable cation channels. While the natural ligands for these channels
      are still unknown, several compounds have been described that either activate or
      inhibit TRPM3 channel activity. experimental approach: We assessed TRPM3-mediated
      gene transcription, which relies on the induction of intracellular signalling to
      the nucleus following activation of TRPM3 channels. Activator protein-1 (AP-1)
      and Egr-1-responsive reporter genes were integrated into the chromatin of the
      cells. This strategy enabled us to analyse gene transcription of the AP-1 and Egr
      1-responsive reporter genes that were packed into an ordered chromatin structure.
      KEY RESULTS: The neurosteroid pregnenolone sulfate strikingly up-regulated AP-1
      and Egr-1 transcriptional activity, while nifedipine and D-erythro-sphingosine,
      also putative activators of TRPM3 channels, exhibited either no or TRPM3
      independent effects on gene transcription. In addition, pregnenolone sulfate
      robustly enhanced the transcriptional activation potential of the ternary complex
      factor Elk-1. Pregnenolone sulfate-induced activation of gene transcription was
      blocked by treatment with mefenamic acid and, to a lesser extent, by the
      polyphenol naringenin. In contrast, progesterone, pregnenolone and rosiglitazone
      reduced AP-1 activity in the cells, but had no inhibitory effect on Egr-1
      activity in pregnenolone sulfate-stimulated cells. CONCLUSION AND IMPLICATIONS:
      Pregnenolone sulfate is a powerful activator of TRPM3-mediated gene
      transcription, while transcription is completely inhibited by mefenamic acid in
      cells expressing activated TRPM3 channels. Both compounds are valuable tools for
      further investigating the biological functions of TRPM3 channels.

PMID- 24895739
TI  - Affective theory of mind in patients with Parkinson's disease: comment.

PMID- 24895740
TI  - Scurvy in an alcohol-dependent patient with a severely unbalanced diet.

PMID- 24895741
TI  - Secondary mania in a patient with solitary red nucleus lesion.

PMID- 24895742
TI  - [Dabigatran versus warfarin in patients with mechanical heart valves].

PMID- 24895743
TI  - Photosensitivity reaction associated with selective serotonin re-uptake
      inhibitors: possible cross-sensitivity?

PMID- 24895744
TI  - [Randomized clinical trial of preventive angioplasty in myocardial infarction].

PMID- 24895745
TI  - [Cystatin C versus creatinine in the determination of risk based on renal
      function].

PMID- 24895746
TI  - Hanns Christian Hopf,MD (1934-2013).

PMID- 24895747
TI  - Author response.

PMID- 24895748
TI  - Author response.

PMID- 24895749
TI  - Isolation of three different bacteriophage from mesophilic Aeromonas sp. that use
      different types of monopolar flagella as their primary receptor.
AB  - Bacteriophage PM4, PM5 and PM6 were isolated on different mesophilic Aeromonas
      strains. These bacteriophage use the flagellum as their primary bacterial
      receptor since purified flagella from these strains are able to inactivate these
      bacteriophages, independently, and the phage-resistant mutants are aflagellate
      and nonmotile. Furthermore, we showed that these bacteriophage may be useful to
      initiate the serotyping of mesophilic Aeromonas for the H-antigen (flagellum).

PMID- 24895750
TI  - Authors' response: multitudes of perspectives: integrating the Selfish Goal model
      with views on scientific metaphors, goal systems, and society.
AB  - In our response, we address commentators' feedback regarding the contributions
      and limitations of the Selfish Goal model. We first clarify potential
      misunderstandings regarding the model's contributions and the role of
      consciousness. Second, we situate evaluations of the selfish metaphor within the
      similarities and differences inherent to the goal-gene comparison. We then
      respond to commentators' insights regarding future directions and implications of
      our model, particularly with respect to the broader organizational systems in
      which goals may operate. Finally, we reiterate important considerations for goal
      research moving forward.

PMID- 24895751
TI  - The role of preclinical SPECT in oncological and neurological  research in
      combination with either CT or MRI.
AB  - Preclinical imaging with SPECT combined with CT or MRI is used more and more
      frequently and has proven to be very useful in translational research. In this
      article, an overview of current preclinical research applications and trends of
      SPECT combined with CT or MRI, mainly in tumour imaging and neuroscience imaging,
      is given and the advantages and disadvantages of the different approaches are
      described. Today SPECT and CT systems are often integrated into a single device
      (commonly called a SPECT/CT system), whereas at present combined SPECT and MRI is
      almost always carried out with separate systems and fiducial markers to combine
      the separately acquired images. While preclinical SPECT/CT is most widely applied
      in oncology research, SPECT combined with MRI (SPECT/MRI when integrated in one
      system) offers the potential for both neuroscience applications and oncological
      applications. Today CT and MRI are still mainly used to localize radiotracer
      binding and to improve SPECT quantification, although both CT and MRI have
      additional potential. Future technology developments may include fast sequential
      or simultaneous acquisition of (dynamic) multimodality data, spectroscopy, fMRI
      along with high-resolution anatomic MRI, advanced CT procedures, and combinations
      of more than two modalities such as combinations of SPECT, PET, MRI and CT all
      together. This will all strongly depend on new technologies. With further
      advances in biology and chemistry for imaging molecular targets and
      (patho)physiological processes in vivo, the introduction of new imaging
      procedures and promising new radiopharmaceuticals in clinical practice may be
      accelerated.

PMID- 24895753
TI  - Paradoxical cardiac memory during permanent his bundle pacing.

PMID- 24895752
TI  - Authors' response: mirror neurons: tests and testability.
AB  - Commentators have tended to focus on the conceptual framework of our article, the
      contrast between genetic and associative accounts of mirror neurons, and to
      challenge it with additional possibilities rather than empirical data. This makes
      the empirically focused comments especially valuable. The mirror neuron debate is
      replete with ideas; what it needs now are system-level theories and careful
      experiments - tests and testability.

PMID- 24895755
TI  - Osmotic stress at the barley root affects expression of  circadian clock genes in
      the shoot.
AB  - The circadian clock is an important timing system that controls physiological
      responses to abiotic stresses in plants. However, there is little information on
      the effects of the clock on stress adaptation in important crops, like barley. In
      addition, we do not know how osmotic stress perceived at the roots affect the
      shoot circadian clock. Barley genotypes, carrying natural variation at the
      photoperiod response and clock genes Ppd-H1 and HvELF3, were grown under control
      and osmotic stress conditions to record changes in the diurnal expression of
      clock and stress-response genes and in physiological traits. Variation at HvELF3
      affected the expression phase and shape of clock and stress-response genes, while
      variation at Ppd-H1 only affected the expression levels of stress genes. Osmotic
      stress up-regulated expression of clock and stress-response genes and advanced
      their expression peaks. Clock genes controlled the expression of stress-response
      genes, but had minor effects on gas exchange and leaf transpiration. This study
      demonstrated that osmotic stress at the barley root altered clock gene expression
      in the shoot and acted as a spatial input signal into the clock. Unlike in
      Arabidopsis, barley primary assimilation was less controlled by the clock and
      more responsive to environmental perturbations, such as osmotic stress.

PMID- 24895756
TI  - Pre-dawn stomatal opening does not substantially enhance  early-morning
      photosynthesis in Helianthus annuus.
AB  - Most C3 plant species have partially open stomata during the night especially in
      the 3-5 h before dawn. This pre-dawn stomatal opening has been hypothesized to
      enhance early-morning photosynthesis (A) by reducing diffusion limitations to CO2
      at dawn. We tested this hypothesis in cultivated Helianthus annuus using whole
      shoot gas exchange, leaf level gas exchange and modelling approaches. One hour
      pre-dawn low-humidity treatments were used to reduce pre-dawn stomatal
      conductance (g). At the whole-shoot level, a difference of pre-dawn g (0.40
      versus 0.17 mol m(-2) s(-1)) did not significantly affect A during the first hour
      after dawn. Shorter term effects were investigated with leaf level gas exchange
      measurements and a difference of pre-dawn g (0.10 versus 0.04 mol m(-2) s(-1))
      affected g and A for only 5 min after dawn. The potential effects of a wider
      range of stomatal apertures were explored with an empirical model of the
      relationship between A and intercellular CO2 concentration during the half-hour
      after dawn. Modelling results demonstrated that even extremely low pre-dawn
      stomatal conductance values have only a minimal effect on early-morning A for a
      few minutes after dawn. Thus, we found no evidence that pre-dawn stomatal opening
      enhances A.

PMID- 24895754
TI  - Low levels of ribosomal RNA partly account for the very  high photosynthetic
      phosphorus-use efficiency of  Proteaceae species.
AB  - Proteaceae species in south-western Australia occur on phosphorus- (P)
      impoverished soils. Their leaves contain very low P levels, but have relatively
      high rates of photosynthesis. We measured ribosomal RNA (rRNA) abundance, soluble
      protein, activities of several enzymes and glucose 6-phosphate (Glc6P) levels in
      expanding and mature leaves of six Proteaceae species in their natural habitat.
      The results were compared with those for Arabidopsis thaliana. Compared with A.
      thaliana, immature leaves of Proteaceae species contained very low levels of
      rRNA, especially plastidic rRNA. Proteaceae species showed slow development of
      the photosynthetic apparatus ('delayed greening'), with young leaves having very
      low levels of chlorophyll and Calvin-Benson cycle enzymes. In mature leaves,
      soluble protein and Calvin-Benson cycle enzyme activities were low, but Glc6P
      levels were similar to those in A. thaliana. We propose that low ribosome
      abundance contributes to the high P efficiency of these Proteaceae species in
      three ways: (1) less P is invested in ribosomes; (2) the rate of growth and,
      hence, demand for P is low; and (3) the especially low plastidic ribosome
      abundance in young leaves delays formation of the photosynthetic machinery,
      spreading investment of P in rRNA. Although Calvin-Benson cycle enzyme activities
      are low, Glc6P levels are maintained, allowing their effective use.

PMID- 24895757
TI  - Secondary metabolite from Nostoc XPORK14A inhibits  photosynthesis and growth of
      Synechocystis PCC 6803.
AB  - Screening of 55 different cyanobacterial strains revealed that an extract from
      Nostoc XPORK14A drastically modifies the amplitude and kinetics of chlorophyll a
      fluorescence induction of Synechocystis PCC6803 cells.After 2 d exposure to the
      Nostoc XPORK14A extract, Synechocystis PCC 6803 cells displayed reduced net
      photosynthetic activity and significantly modified electron transport properties
      of photosystem II under both light and dark conditions. However, the maximum
      oxidizable amount of P700 was not strongly affected. The extract also induced
      strong oxidative stress in Synechocystis PCC 6803 cells in both light and
      darkness. We identified the secondary metabolite of Nostoc XPORK14A causing these
      pronounced effects on Synechocystis cells. Mass spectrometry and nuclear magnetic
      resonance analyses revealed that this compound, designated as M22, has a non
      peptide structure. We propose that M22 possesses a dualaction mechanism: firstly,
      by photogeneration of reactive oxygen species in the presence of light, which in
      turn affects the photosynthetic machinery of Synechocystis PCC 6803; and
      secondly, by altering the in vivo redox status of cells, possibly through
      inhibition of protein kinases.

PMID- 24895759
TI  - Yellow Biotechnology. Preface.

PMID- 24895758
TI  - Altered growth and improved resistance of Arabidopsis  against Pseudomonas
      syringae by overexpression of the  basic amino acid transporter AtCAT1.
AB  - Amino acid transporters in plants are crucial for distributing amino acids
      between plant organs and cellular compartments. The H(+)-coupled plasma membrane
      transporter CAT1 (cationic amino acid transporter 1) facilitates the high
      affinity uptake of basic amino acids. The uptake of lysine (Lys) via the roots
      was not altered in loss-of-function mutants, in accordance with the minor
      expression of CAT1 in roots, but plants ectopically overexpressing CAT1
      incorporated Lys at higher rates. Exogenous Lys inhibited the primary root of
      Arabidopsis, whereas lateral roots were stimulated. These effects were augmented
      by the presence or absence of CAT1. Furthermore, the total biomass of soil-grown
      plants ectopically overexpressing CAT1 was reduced and the time to flowering was
      accelerated. These effects were accompanied by only minor changes in the overall
      amino acid profile. Interestingly, CAT1 belongs to a specific small cluster of
      nitrogen-containing metabolite transporter genes that are rapidly up-regulated
      upon infection with Pseudomonas syringae and that may participate in the systemic
      response of plants to pathogen attack. The overexpression of CAT1 indeed enhanced
      the resistance to the hemibiotrophic bacterial pathogen P. syringae via a
      constitutively activated salicylic acid (SA) pathway, which is consistent with
      the developmental defects and the resistance phenotype.

PMID- 24895760
TI  - Reply to Lukas and Clutton-Brock: Infanticide still drives primate. monogamy.

PMID- 24895761
TI  - Reply to Rehm: Why rates of upslope shifts in tropical species vary is an open
      question.

PMID- 24895762
TI  - Latest technology in biosensors.

PMID- 24895763
TI  - Authors' response.

PMID- 24895764
TI  - Authors' response.

PMID- 24895765
TI  - Transesophageal echocardiography for transmyocardial laser revascularization.

PMID- 24895766
TI  - Authors' response.

PMID- 24895768
TI  - Author's response.

PMID- 24895769
TI  - Why your vote counts.

PMID- 24895767
TI  - Author's response.

PMID- 24895770
TI  - Unite in a Day of Action.

PMID- 24895771
TI  - Taking the time to reflect.

PMID- 24895772
TI  - An introduction to velocity-map imaging mass spectrometry (VMImMS).
AB  - This account introduces a new variant of time-of-flight mass spectrometry, termed
      velocity-map imaging mass spectrometry (VMImMS). While the ion abundances
      recorded in conventional ToF-MS measurements are highly useful for molecular
      quantification and structure determination, the final parent and fragment ion
      yields are Largely blind to the dynamics of the processes in which the ions were
      formed inside the mass spectrometer. By recording the velocity distribution of
      each ion in tandem with the mass spectrum, not only can the details of the
      dissociative ionisation dynamics be unravelled, but the extra dimensions of
      information can be used for enhanced molecular fingerprinting, separating
      contributions from ions with identical mass-to-charge ratio and resolving
      components within mixtures, to name but a few examples. Measuring ion-velocity
      distributions within a mass spectrometry measurement is not new, but
      incorporating imaging techniques developed within the reaction dynamics community
      provides vastly improved velocity resolution for all ions simultaneously in a
      single-stage instrument. This account provides an introduction to VMImMS,
      outlines the fundamental instrumentation and detector requirements and the
      challenges associated with developing the method further, and details proof-of
      concept work from our Laboratory on a number of potential applications of the
      technique.

PMID- 24895773
TI  - Space-charge effects in an electrostatic multireflection ion trap.
AB  - The multireflection ion traps with isochronous properties offer a Lot of
      opportunities for time-of-flight mass spectrometry by elongation of the ion path,
      thus preserving the compact dimensions of an instrument. We have built and tested
      a two-mirror linear trap that provides at least 80,000 mass-resolving power.
      Although the mass resolution appears promising, there are substantial limitations
      that arise from Coulomb interactions of the trapped ions. Among these, the mutual
      repulsion of ions with same or close mass-to-charge ratios appears dominant,
      resulting in counterintuitive motion synchronization. The self-bunching and
      coalescence effects are also examined by numerical simulation.

PMID- 24895774
TI  - Design, simulation and evaluation of improved air amplifier incorporating an ion
      funnel for nano-ESI MS.
AB  - An improved air amplifier design that takes advantage of the combined effects of
      aerodynamic and electrodynamic focusing was developed to couple a
      nanoelectrospray ionisation (nano-ESI) source and the heated mass spectrometer
      inlet to improve the sensitivity of a mass spectrometer. The new design comprises
      an electrodynamic ion funnel integrated into the main air pathway of the air
      amplifier to more effectively focus and transmit gas-phase ions from the nano-ESI
      source into the heated mass spectrometer inlet. Numerical computational fluid
      dynamics simulations were carried out using a commercial software package, ANSYS
      FLUENT, to provide more detailed information about the device's performance. The
      gas flow field as well as the electric field patterns and the Lagrangian ion
      motion were conveniently simulated using this single package and custom-written,
      user-defined functions. Experimental results show a nearly five-fold improvement
      in reserpine ion intensity with the air amplifier operated at a nitrogen gauge
      pressure of 40 kPa and no direct current (DC) or radiofrequency (RF) potentials
      applied to the ion funnel when the distance between the electrospray emitter and
      sampling inlet tube was 24 mm, as compared to direct sample infusion from the
      same distance without the air amplifier. More importantly, a nearly three-fold
      additional gain in ion intensity was measured when both DC and RF potentials were
      co-applied, resulting in more than a 13-fold overall ion intensity gain which
      could be attributed to the combined air amplifier aerodynamic and ion funnel
      electrodynamic focusing effect.

PMID- 24895775
TI  - Wide-range mass calibration for negative-ion DART mass spectrometry.
AB  - A method for accurate mass calibration covering a wide m/z range in negative-ion
      direct analysis in real time mass spectrometry (DART-MS) is described. It is
      based on a commercially available tuning solution (Agilent ES tune mix) normally
      applied in electrospray ionization. This acetonitrile solution is composed of
      ammonium trifluoroacetate, betaine, 2,4,6-tris(heptafluoropropyl)-1,3,5-triazine,
      and various symmetrical hexakis-(fluoroalkoxy)-phosphazenes. Upon addition of 2%
      (v/vl trifluoroacetic acid in negative-ion DART-MS, this mixture yields negative
      ions covering a range of m/z 69 to m/z 2834. Validity of the calibration
      procedure is demonstrated on a Fourier transform ion cyclotron resonance mass
      spectrometer by application to polyethylene glycol diacid and [60]fullerene.
      Experimental conditions and a mass reference list are provided.

PMID- 24895776
TI  - Formation of curcumin molecular ion under electrospray ionisation conditions in
      the presence of metal cations.
AB  - Electrospray ionisation (ESI) mass spectra obtained for solutions containing
      curcumin, copper cation and other metal cations, namely Co2+, Ni2+, Mn2+ and
      Zn2+, have shown an abundant curcumin molecular ion at m/z 368. This ion was not
      formed for solutions containing curcumin and copper cations or for those
      containing curcumin and other metal cations. To the best of our knowledge, it is
      the first example of a system in which copper cations and other metal cations
      promote formation of organic radical cation under ESI conditions.

PMID- 24895777
TI  - Electrospray ion mobility mass spectrometry of positively charged sodium bis[2
      ethythexyl)sulfosuccinate aggregates.
AB  - Collision cross-sections (CCS) of positively singly and multiply charged
      aggregates of the surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) in
      the gas phase have been measured by quadrupole ion mobility time-of-flight mass
      spectrometry. Calibration of the observed drift times to the CCS of the AOTNa non
      covalent aggregates was achieved by collecting, under the same experimental
      conditions, the drift times of a range of singly and multiply charged polyalanine
      peptides whose CCS had been obtained by conventional ion mobility spectrometry.
      Together with an obvious increase of the aggregate cross-section with the
      aggregation number, it was found that the aggregate cross-section increases with
      the charge state due to the sodium counterions steric effect and the augmented
      electrostatic repulsion. This finding is consistent with the result of a previous
      molecular dynamics study on positively charged AOTNa aggregates in the gas phase
      showing that, by increasing the charge state, the aggregates become progressively
      more oblate; implying a rise of their CCS. Moreover, the occurrence at each
      aggregation number and extra charge of a unique value of cross section points
      toward aggregates whose conformations do not show discernible shape change in the
      experiment time scale.

PMID- 24895778
TI  - Utilisation of gas-phase ion-molecule reactions for differentiation between
      phospho- and sulfocarbohydrates.
AB  - Gas-phase ion-molecule reactions of four boron-containing neutrals were explored
      as a means for differentiation between isobaric phospho- and sulfocarbohydrates.
      Phosphorylation and sulfation impose an addition of 80 Da to the molecular mass,
      so for low-resolution mass spectrometers compounds that have such modifications
      will appear at the same nominal mass-to-charge (m/z) ratio. However, the ions of
      these isobaric species behave differently in ion-molecule reactions. All four
      evaluated neutral molecules [trimethyl borate (TMB), triethyl borate (TEB),
      diethylmethoxyborane (DEMB) and diisopropoxymethylborane (DIPMB)] proved to be
      reactive towards phosphorylated sugars and unreactive towards sulfated
      carbohydrates. In addition, TMB and TEB were found suitable for distinguishing
      positional isomers of phosphorylated carbohydrates, while reactions with DEMB and
      DIPMB were successful in differentiating phosphorylated, sulfated and unmodified
      deprotonated sugars. Similar reactions in the positive ion mode (alkali
      cationised) were found to be less conclusive.

PMID- 24895779
TI  - Analysis of new synthetic drugs by ion mobility time-of-flight mass spectrometry.
AB  - Characteristic ion mobility mass spectrometry data, reduced mobility, and limits
      of detection (signal-to-noise ratio = 3) were determined for six synthetic drugs
      and cocaine by ion mobility time-of-flight mass spectrometry (IM-TOF-MS) with
      electrospray ionization (ESI) and atmospheric pressure chemical ionization
      (APCI). The studied synthetic illicit drugs recently appeared on the recreational
      drug market as designer drugs and were methylone, 4-MEC (4'-methylethcathinone),
      3,4-MDPV (3,4-methylenedioxypyrovalerone), JWH-210 [4-ethylnaphthalen-1-yl-(1
      pentylindol-3-yl)methanone], JWH-250 [2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3
      yl)ethanone], and JWH-203 [1-pentyl-3-(2'-chlorophenylacetyl) indole]. Absolute
      reduced mobilities in nitrogen were 1.35, 1.28, 1.41, 1.30, 1.18, 0.98, 1.09, and
      1.07 cm2V(-1)s(-1), for methylone [M-H]+, methylone [M+H]+, 4-MEC [M-H]+, 4-MEC
      [M+H]+, 3,4-MDPV [M+H]+, JWH-210 [M+H]+, JWH-250 [M+H]+, and JWH-203 [M+H]+,
      respectively. Selected illicit drugs are easily identified by IM-TOF-MS during a
      100s analysis. Relative Limits of detection ranged from 4 to 400 nM are
      demonstrated for these compounds. Such relative limits of detection correspond to
      14 pg to 2 ng absolute limits of detection. Better detection limits are obtained
      in APCI mode for all the illicit drugs except cocaine. ESI mode was found to be
      preferable for the IM-TOF-MS detection of cocaine at trace levels. A single
      sample analysis is completed in an order of magnitude less time than that for
      conventional liquid chromatography/mass spectrometry approach. The application
      allows one to consider IM-TOF-MS as a good candidate for a method to determine
      quickly the recently surfaced designer drugs marketed on the internet as "bath
      salts," "spice," and "herbal blends".

PMID- 24895780
TI  - Study on the mechanism of ferrite-induced dinitrophenol photodegradation.
AB  - We report here the effectiveness of gas chromatography mass spectrometry
      techniques in establishing the ferrite-associated photocatalytic degradation
      mechanism of pesticide 2,4-dinitrophenol (2,6-DNP). Unlike the previously
      discussed DNP-degradation mechanisms that involve either oxidation or reduction
      reactions, ferrite-based ultraviolet (UV) photodegradation of DNP affords the
      nontoxic 6-hydroxy-3,5-dinitrohexa-2,4-dienal by an unusual water addition to the
      benzene core. We searched for and demonstrated the presence of an epoxide of DNP
      within the photodegradation process, which may unambiguously explain the novel
      photochemical mechanism. During the 15 min UV photoinduced process, DNP
      degradation efficiency on the zinc ferrite catalyst was calculated to be 82%,
      whereas the first-order kinetic rate constant k was as high as 3.4 x 10(-2)min(
      1).

PMID- 24895781
TI  - Characterization of volatile and semi-volatile compounds in green and fermented
      leaves of Bergenia crassifolia L. by gas chromatography-mass spectrometry and ID
      CUBE direct analysis in real time-high resolution mass spectrometry.
AB  - Chemical compositions of volatile and semi-volatile components in green and
      fermented leaves of Bergenia crassifolia L. were studied. Leaf components were
      identified using gas chromatography with low resolution mass spectrometry and
      direct analysis in real time (DART) high resolution mass spectrometry with an ID
      CUBE ion source. Phytol, nerolidol, geraniol, linalool, alpha-bisabolol, alpha
      bisabololoxide B, alpha-cadinol, delta-cadinene, alpha-terpineol and several
      other marker compounds of special interest were defined, for which the process of
      fermentation significantly changed their content in the leaves. Low resolution El
      GC-MS and ID-CUBE DART-HRMS were found to be complementary methods, as they
      provide different information, helpful to increase the confidence of
      identification.

PMID- 24895782
TI  - Lovastatin inhibited the growth of gastric cancer cells.
AB  - BACKGROUND/AIMS: Gastric cancer cells required large amount of cholesterol to
      grow and proliferate. The objective of this study was to examine whether the
      growth of gastric cancer cells was inhibited in vivo by using lovastatin, an
      effective cholesterol-lowing drug. METHODOLOGY: The mice models for gastric
      cancer cells MKN45 were divided into two groups, the control and experimental
      group. Lovastatin was administered orally to the experimental group, while saline
      given to the control group. We measured the volume and weight of tumors, and
      calculated RTV (relative tumor volume), T/C (relative added value of tumor) and
      the inhibition rate. Then the expression levels of PCNA in gastric cancer tissues
      were examined immunohistochemically. RESULTS: The volume of tumors in the control
      and experimental groups was 3.801 +/- 1.078 and 3.325 +/- 0.745, respectively (p
      > 0.05), while RTV was 49.684 +/- 12.250 and 42.506 +/- 10.515, respectively (p >
      0.05). T/C, an indication of antitumor, was 85.55%. The weight of tumors of the
      mice in control and experimental group was 3.23 +/- 0.43 and 2.65 +/- 0.58,
      respectively (p < 0.05). The inhibition rate was 20.48%. The PCNA index in the
      lovastatin group was 32.35 +/- 6.43%, while in the control group was 91.24 +/-
      6.59%. The PCNA index of lovastatin group was much lower (P < 0.01). CONCLUSIONS:
      Lovastatin inhibited the growth of gastric cancer cells.

PMID- 24895783
TI  - Circulating cancer cells are potential weapon for future generations.
AB  - As metastatic "seeds," CTCs are believed to be responsible for dissemination from
      a primary tumor to anatomically distant organs. For the most epithelial tumors
      the presence of CTCs is associated with tumor progression, increased risk of
      local and regional recurrence as well as the development of distant metastases.
      CTCs could be used as a strong prognostic and predictive marker for patient's
      clinical outcome and survival. A considerable number of promising CTC-detection
      techniques based on molecular and immunologic methods have been developed in
      recent years. Most of them need an enrichment step to improve sensibility and/or
      specificity.

PMID- 24895785
TI  - What is an adequate surgical management for pTis and pT1 early ampullary
      carcinoma?
AB  - BACKGROUND/AIMS: The aim of this study is to identify an adequate surgical
      management for early ampullary carcinoma (AC). METHODOLOGY: We retrospectively
      reviewed a total of 51 patients who underwent a curative pancreaticoduodenectomy
      (PD) for various stages of AC. RESULTS: A pathological early AC was defined as
      pTis and pT1 in this study. Of the 51 AC patients, 7, 13, 17, 13 and 1 were
      confirmed to be pTis, pT1, pT2, pT3, and pT4, respectively. The incidence of
      lymph node metastasis in pTis and pT1 patients was 0% and 0%, respectively, while
      the incidence of lymphatic invasion was 0% and 38.5%, respectively. These two
      pathological factors significantly correlated with the advancement of tumor
      invasion. Multivariate analysis demonstrated that lymph node metastasis and
      lymphatic invasion were the only significant independent predictors of survival.
      In 20 early AC patients, tumor recurrence was detected in 2 (10%) cases in which
      the tumor stage was pT1, and lymphatic invasion was evident. CONCLUSIONS:
      Although PD is the gold standard operation for all ACs, less invasive surgery,
      such as ampullectomy, could be indicated for patients with pTis AC following a
      strict preoperative evaluation of tumor staging.

PMID- 24895784
TI  - Modified arterioportal shunting in radical resection of hilar cholangiocarcinoma.
AB  - BACKGROUND/AIMS: The resection and reconstruction of hepatic artery is often
      required in radical surgery for hilar cholangiocarcinoma. In this study, we
      reported our experience in performing the arterioportal shunting with restriction
      of the arterial caliber as an alternative for the arterial reconstruction on the
      basis of our experiment when reconstruction of hepatic artery is impossible.
      METHODOLOGY: Eight patients with hilar cholangiocarcinoma underwent extended left
      hepatectomy and caudate lobectomy combined with en bloc resection of hepatic
      artery and arterioportal shunting with restriction of the arterial caliber. The
      efficacy of arterioportal shunting and restriction of the arterial caliber in
      preventing complications of arterioportal shunting were assessed by computed
      tomography angiography (CTA) perioperational period and 2 years follow-up after
      the operation. RESULTS: Eight patients recovered uneventfully without any
      complication. CTA showed a patent shunt and normal liver regeneration. No signs
      of portal hypertension were found in two years of follow-up. CONCLUSIONS:
      Arterioportal shunting with restriction of the arterial caliber appears to be a
      feasible and safe alternative for the microvascular reconstruction after hepatic
      artery resection in radical surgery for hilar cholangiocarcinoma.

PMID- 24895786
TI  - Laparoscopic cholecystectomy in acute cholecystitis in the elderly.
AB  - BACKGROUND/AIMS: Benefits of using laparoscopic cholecystectomy (LC) in the
      elderly with acute cholecystitis (AC) is still questionable. Our aim is to carry
      out a comparative analysis of that intervention in two groups of patients: under
      65 years old, and over or equal to 65 years old. METHODOLOGY: This study
      corresponds to 249 LCs carried out during 4 years at the Emergency and Surgery
      Department of Hospital de S. Joao; 2 groups of individuals were considered: group
      A--under 65 years old, and group B--65 years old or over. The first consisted of
      168 cases (88 men and 80 women, mean age 48.34 years (+/- 11.80)); and the second
      included 81 patients (40 men and 41 women, mean age 75.73 years (+/- 6.87)). The
      diagnosis was made on the basis of clinical symptoms, leukocytosis and
      ultrasound. RESULTS: The comparative analysis between these two groups provided
      the following results: 1) Mortality: 0% in A vs. 4.76% in B (P = 0.007); 2)
      Overall postoperative complications: 5.36% in A vs. 22.2% in B (P < 0.001); 3)
      Surgical complications: 4.76% in A vs. 14.8% in B (P = 0.468); 4) Intraoperative
      complications: 4.76% in A vs. 4.94% in B (P = 0.007); 5) Reoperations: 2.98% in A
      vs. 7.41% in B (P = 0.022); 6) Conversion: 12.50% in A vs. 17.28% in B (P =
      0.447); 7) Lesion of the Main Bile Duct: 1.79% in A vs. 2.47% in B (P = 0.447);
      8) Hospital Stay, equal to or less than 4 days: 72.62% in A vs. 27.16% in B (P
      <0.001). CONCLUSIONS: LC is a safe and efficient intervention in the treatment of
      acute cholecystitis in the elderly, although with greater morbidity and longer
      hospital stay, when compared with younger patients.

PMID- 24895787
TI  - Clinical efficacy of metallic biliary stents combined with different anti-cancer
      treatments in the management of bile duct cancer.
AB  - BACKGROUND/AIMS: The appropriate selection of an anti-cancer treatment after
      biliary stenting for bile duct cancer and the effects of new anti-cancer
      treatments are unclear. To determine the clinical efficacy of metallic biliary
      stents combined with different anticancer treatments in the management of bile
      duct cancer. METHODOLOGY: We compared 49 patients with bile duct cancer who
      underwent biliary stenting plus anticancer treatment with 60 patients who
      underwent stenting alone (controls) in our hospital, between December 1998 and
      December 2012. RESULTS: In the combined-treatment group, 23 patients underwent
      three-dimensional radiation therapy, 21 underwent chemotherapy, and 5 underwent
      both three-dimensional radiation therapy and chemotherapy. The survival rate
      (chi2 = 41.563, P = 0.000) and duration of stent patency (chi2 = 50.268, P =
      0.000) were significantly greater in the combined-treatment group than the
      control group. Adverse reactions were observed .The patients in the combined
      treatment group developed nausea, vomiting and leukopenia, which were cured with
      symptomatic treatment. No biliary stent-related complications occurred in either
      group. CONCLUSIONS: Metallic biliary stent insertion combined with different anti
      cancer treatments can increase survival and stent patency rates in bile duct
      cancer patients. This combination treatment was safe and effective.

PMID- 24895788
TI  - Management of postoperative bilomas and biliary injuries associated with
      laparoscopic cholecystectomy with intrabiliary ethanol ablation and micro-coil
      embolization.
AB  - Laparoscopic cholecystectomy (LC) is the treatment of choice for gallbladder
      stones. One of the major complications associated with LC is bile duct injury;
      ligation or cutting of a bile duct can result in significant segmental biliary
      obstruction with cholangitis or bile leak, which can progress to bile peritonitis
      or biliary fistula. Most postoperative bilomas and bile leaks can be treated by
      percutaneous drainage and decompression of the biliary system by endoscopic stent
      placement or nasobiliary drainage. When conservative methods fail despite
      prolonged drainage, selective intrahepatic biliary ethanol and micro-coil
      embolization may be an alternative treatment. We report three successful cases
      where postoperative bilomas associated with laparoscopic cholecystectomy have
      been managed with intrabiliary ethanol ablation and micro-coil embolization.

PMID- 24895789
TI  - Pilot study of stereotactic body radiation therapy combined with transcatheter
      arterial chemoembolization for small hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: We retrospectively evaluated the local tumor control and safety
      of transcatheter arterial chemoembolization (TACE) followed by stereotactic body
      radiation therapy (SBRT) for small hepatocellular carcinoma (HCC) in this pilot
      study. METHODOLOGY: Twenty-eight patients not for the indication of hepatectomy
      or ablation procedures were enrolled in this study. Eligible criteria was as
      followed: i) less than 3 hypervascular HCC nodules, each up to 30 mm in diameter;
      ii) not suitable for the hepatic resection or ablative therapy; iii) Child
      Turcotte-Pugh (CTP) score < or = 7. SBRT was performed within 1-2 months after
      TACE. Treatment efficacy was evaluated, according to the Response Evaluation
      Criteria in Cancer of the Liver (RECICL). RESULTS: The median local tumor control
      time was not reached. The 1-year cumulative local tumor control rate was 96.3%.
      The median disease-free survival time was 18 months. The 1- year cumulative
      overall survival rate was 92.6%. One patient (3.6%) died due to intrahepatic
      ectopic multiple recurrence and systemic metastasis and one (3.6%) due to
      cerebral hemorrhage. No patients experienced severe acute hematologic or physical
      toxicity or radiation induced liver damage. CONCLUSIONS: Our study demonstrated
      SBRT combined with TACE is a safe and effective modality of the locoregional
      therapy for small primary HCC.

PMID- 24895790
TI  - Doppler perfusion index and contrast-enhanced ultrasound in patients with
      colorectal cancer liver metastases.
AB  - BACKGROUND/AIMS: To assess the value of the Doppler perfusion index (DPI) and
      contrast agent for the detection of liver metastases in patients with colorectal
      cancer. METHODOLOGY: DPI was measured in 18 patients with colorectal cancer liver
      metastases and 18 control subjects. Sixteen patients were underwent contrast
      enhanced ultrasonography (CEUS). RESULTS: patients with liver metastases had
      significantly greater DPI than control group (0.39 +/- 0.10 vs. 0.19 +/- 0.07, p
      < 0.05). Sixteen liver metastasis lesions underwent a rapid wash-out of contrast
      agent during the portal venous phase followed by a complete wash-out of SonoVue
      during the sinusoidal phase and were differentiated as "fast-in and fast-out"
      contrast enhancement patter. Another 3 lesions which were not found by baseline
      ultrasonography were detected to be enhancement defects at sinusoidal phases by
      CEUS. CONCLUSIONS: DPI is a sensitive index in detection of colorectal liver
      metastases; if used combined with contrast agent, much more occult liver
      metastasis would be detected by ultrasonography.

PMID- 24895791
TI  - Portal hemodynamics before and after liver resection and its correlation with
      post-hepatectomy liver failure in patients with Child-Pugh class A: analysis of
      151 consecutive cases.
AB  - BACKGROUND/AIMS: Low portal velocity (PV) was found in cirrhotic patients, which
      was thought to be a risk factor for post-hepatectomy liver failure (PHLF). This
      study attempted to find out whether a correlation existed between portal
      hemodynamics and PHLF. METHODOLOGY: From December 2010 to December 2012, all
      consecutive patients with Child-Pugh class A underwent liver resection were
      included. PV and PF were measured by using Doppler ultrasound preoperatively and
      on postoperative day 3. Portal hemodynamics change was explored. Univariable and
      multivariable analysis were used to identify risk factors for PHLF. RESULTS: PHLF
      occurred in 25 of 151 patients, and persistent PHLF in 9 patients. Mean portal
      velocity change (PVmeanC) was significantly different between patients with PHLF
      and patients without PHLF, but it failed to be identified as independent
      predictor for PHLF in multivariate analysis, which found alanine aminotransferase
      (ALT) and Ishak score significantly associated with PHLF, and only ALT
      significantly associated with persistent PHLF. Subgroup analysis of the 73
      cirrhotic patients also showed that none of the portal hemodynamic parameters
      were independent risk factors for PHLF or persistent PHLF. CONCLUSIONS: None of
      the portal hemodynamic parameters could be used to predict PHLF or persistent
      PHLF.

PMID- 24895792
TI  - Risk factors of portal vein thrombosis in patients with beta thalassemia major
      after splenectomy: laparoscopic versus open procedure.
AB  - BACKGROUND/AIMS: Beta thalassemia major patients are at a high risk of
      thromboembolic events due to a hypercoagulable state, and nowadays laparoscopic
      splenectomy (LS) has become the standard surgical procedure for many benign
      diseases. The aim of this study is to show our experience of LS for beta
      thalassemia major, and to explore predictive factors for portal vein thrombosis
      (PVT) after splenectomy. METHODOLOGY: We performed a retrospective chart review
      of 25 cases of LS (Group 1) and 34 cases of open splenectomy (OS, Group 2) in
      beta thalassemia major patients. Patients' perioperative, intraoperative and
      postoperative information was recorded and compared. RESULTS: Compared with Group
      2, patients in Group 1 had significantly increasing operative time, less
      estimated blood loss (EBL), decreasing postoperative stays, and shorter duration
      of oral intake. Related variables were assessed by univariate and multivariate
      logistic regression analyses, indicating splenic weight (cutoff value: 1311.5 g)
      was a significant independent predictor for PVT after LS. Regardless of LS or OS,
      some patients responded to splenectomy completely, while some responded
      partially. CONCLUSIONS: According to this study, LS is associated with better
      surgical outcomes for beta thalassemia major compared with OS. Patients receiving
      LS may be susceptible to PVT, and splenic weight can be used as a predictor.

PMID- 24895793
TI  - Monocyte chemotactic protein-1 as possible prognostic markers of the efficacy of
      antiviral treatment in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Antiviral therapy with interferon and ribavirin had been proved
      to be effective in Hepatitis C treatment. However, the valuable markers for
      monitoring the efficacy of antiviral therapy are required clinically. The present
      study aimed to evaluate the association between pretreatment levels of Monocyte
      chemoattractant protein-1 levels (MCP-1) and the virological response in treated
      patients with chronic hepatitis C infection. METHODOLOGY: Concentrations of MCP-1
      in serum were determined in 165 patients with chronic hepatitis C (CHC) treated
      with interferon and ribavirin by enzyme linked immunosorbent assay before and 48
      weeks after cessation of therapy. RESULTS: Pretreatment MCP-1 levels in patients
      with sustained virological response (SVR) were significantly lower than in non
      responders (Non-SVR) (220.2 +/- 31.7 vs. 305.6 +/- 50.7 pg/mL, p = 0.009) and MCP
      1 significantly decreased in patients with SVR (form 220.2 +/- 31.7 pg/mL to
      140.2 +/- 26.7 pg/mL; p <0.01) but not in Non-SVR (form 305.6 +/- 50.7 pg/mL to
      286.6 +/- 41.9 pg/mL; p = 0.17) after 48 weeks of treatment. By multivariate
      analysis, non-1 genotype was independent predictors of SVR in all patients. When
      multivariate analysis was restricted to patients with non-1 genotype, only
      pretreatment MCP-1 levels were identified as predictive factors of SVR.
      CONCLUSIONS: MCP-1 may be a prognostic marker of the efficacy of antiviral
      therapy in CHC patients.

PMID- 24895794
TI  - Evaluation of relationship between serum lipids levels with colorectal carcinoma:
      a single center prospective case control study.
AB  - BACKGROUND/AIMS: To evaluate association of serum lipids and fasting plasma
      glucose levels with colorectal cancer. METHODOLOGY: This prospective case control
      study was conducted with 347 patients with colorectal carcinoma and 310 age and
      gender matched healthy controls who were examined for annual check-up. Total
      cholesterol, serum lipids and fasting glucose levels were measured in both
      groups. Body weight and body mass indices were also evaluated. RESULTS: The mean
      serum cholesterol level was 167.4 +/- 43.6 mg/dL for patients with colorectal
      cancer and 210.1 +/- 30.7 mg/dL for controls. The mean fasting plasma glucose
      levels for both groups were respectively 107.7 +/- 22.4 and 90.2 +/- 10.3.
      Between the colorectal cancer and control groups, there was a statistically
      significant difference in fasting plasma glucose and serum lipid levels except
      LDL-C. Serum total cholesterol level was even lower in advanced stages of cancer.
      CONCLUSIONS: Our study suggests that there is an inverse association between low
      serum total cholesterol levels and colorectal cancer. Since cholesterol levels
      were lower in the advanced stages of colorectal cancer it is possible that low
      levels of serum cholesterol levels were a consequence of colorectal cancer. The
      association with hypertriglyceridemia and high fasting plasma glucose levels
      suggest the role of hyperinsulinemia in colorectal carcinogenesis.

PMID- 24895795
TI  - Clinical outcomes of colonic mucosal cancers with histologically positive or
      uncertain resection margin after endoscopic resection.
AB  - BACKGROUND/AIMS: Although incomplete endoscopic resection of colonic neoplasms
      can lead to the development of interval invasive cancer, few studies have
      assessed clinical outcomes after histologically incomplete resection of colonic
      mucosal cancer. We aimed to evaluate the clinical outcomes of patients with
      histologically positive or uncertain resection margins after endoscopically
      complete resection of colonic mucosal cancer. METHODOLOGY: We analyzed the
      clinical course of 38 patients (median 62 years, male:female = 27:11) who
      underwent endoscopically complete resection of colonic mucosal cancer, but who
      showed histologically positive or uncertain resection margins. RESULTS: The
      median size of the 38 colonic mucosal cancers was 14 mm (range, 5-50 mm). Of
      these, 20 were resected by a piecemeal resection, and had uncertain histological
      resection margins. The remaining 18 patients underwent en-bloc resection; of
      these, 16 had uncertain resection margins and 2 had positive margins. Patients
      underwent a median of 2.3 follow-up endoscopies (range, 1-7) during a median
      follow-up time of 18.3 months (range, 3-75 months). No local or distant
      recurrence was detected. CONCLUSIONS: Cautious followup without immediate
      additional treatment can be considered for patients who undergo endoscopically
      complete resection of colonic mucosal cancers, even when histological examination
      shows uncertain or positive resection margins.

PMID- 24895797
TI  - Endoscopic manifestations of primary colorectal lymphoma.
AB  - BACKGROUND/AIMS: Little is known about the endoscopic manifestations of primary
      colorectal lymphoma. The study was designed to describe the features of
      colonoscopy and endoscopic ultrasonography of primary colorectal lymphoma.
      METHODOLOGY: twenty-five patients with a definite diagnosis of primary colorectal
      lymphoma were recruited in this study. Their colonoscopic and endoscopic
      ultrasonography manifestations were retrospectively reviewed. RESULTS: Based on
      colonoscopic features, primary colorectal lymphomas were classified into three
      subtypes: ulcerative type (n = 16, 64%), polypoid type (n = 4, 16%), and massive
      type (n = 5, 20%). Thirteen (92.9%) of the 14 patients with T-cell lymphomas
      presented as ulcerative lesions, and 3 (27.3%) of the 11 patients with B-cell
      lymphomas presented as ulcerative lesions (92.9% vs. 27.3%, p = 0.002). The
      initial diagnose accordance rate of colonoscopy was only 28% for primary
      colorectal lymphomas. The endosonography features of primary colorectal lymphomas
      included disappearance of normal colorectal layers, diffuse hypoechoic lesions
      instead, and thickening of intestinal wall. CONCLUSIONS: Primary colorectal T
      cell lymphoma presented as ulcerative lesions more frequently than B-cell
      lymphoma. It was difficult to differentiate primary colorectal lymphoma from
      other diseases merely based on colonoscopy. Endoscopic ultrasonography was useful
      in the diagnosis of primary colorectal lymphoma.

PMID- 24895796
TI  - Rectal gastrointestinal stromal tumor: clinical features, endoscopic findings and
      prognosis.
AB  - BACKGROUND/AIMS: Rectal gastrointestinal stromal tumor (GIST) accounts for only a
      small portion of all GISTs, and reports regarding its clinical features and
      endoscopic findings are still lacking. METHODOLOGY: Thirty-two patients diagnosed
      as rectal GIST at Asan Medical Center, a tertiary university hospital in Korea
      between May 2003 and January 2011 were enrolled. RESULTS: The median age was 54
      years (range, 31-79) with 18 males (56.2%). Common symptoms were hematochezia,
      anal pain, and defecation difficulty, although 11 patients were asymptomatic. The
      median size of tumor was 6.1 cm (range, 0.4-12.0 cm), and the median distance
      from the anal verge was 4 cm (range, 3 cm). The most common endoscopic finding
      was subepithelial tumor with normal overlying mucosa (63.1%), followed by
      subepithelial tumor with erosion, ulceration, or bleeding (31.6%). Preoperative
      imatinib was administered in eight patients (25.0%) that helped the downsizing
      the tumor and anal sphincter preserved. High-risk group by NIH risk
      classification and tumor size were associated with tumor recurrence, with the
      overall five-year recurrence-free survival of 67.2%. CONCLUSIONS: Common
      endoscopic feature of rectal GIST was subepithelial tumor with normal mucosa.
      Patients treated by definite resection with or without imatinib for rectal GIST
      seem to show a favorable clinical course.

PMID- 24895798
TI  - Fast track programmes vs. traditional care in laparoscopic colorectal surgery: a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND/AIMS: To assess the efficacy and safety of fast track (FT) programmes
      in laparoscopic colorectal surgery by comparing FT programmes with traditional
      care in randomized controlled trials (RCTs). METHODOLOGY: RCTs comparing the
      effects of FT programmes and traditional care in the same context of laparoscopic
      colorectal surgery were found on PubMed, EMBASE and Cochrane Library. Primary
      hospital stay, overall hospital stay, readmission rate, morbidity and mortality
      were assessed. RESULTS: Four original RCTs investigating a total of 486 patients,
      of whom 235 received FT programmes and 251 received traditional care, met the
      inclusion criteria. The pooled weighted mean difference in primary hospital stay
      and overall hospital stay was -1.22 (95% CI: -1.57 to -0.87) and -1.00 (95% CI: 
      1.48 to -0.52), which showed a significant reduction with use of FT programmes (p
      < 0.05). The pooled odds ratio for readmission rate, morbidity and mortality was
      0.85 (95% CI: 0.33 to 2.21), 0.68 (95% CI: 0.44 to 1.04) and 1.51 (95% CI: 0.29
      to 7.77), suggesting no significant difference between the two groups (p > 0.05).
      CONCLUSIONS: FT programmes in elective laparoscopic colorectal surgery could
      significantly reduce primary hospital stay and overall hospital stay, and with no
      significant difference in readmission rate, morbidity and mortality compared with
      traditional care.

PMID- 24895800
TI  - Is microvessel density correlated with anastomotic leakage after low anterior
      resection?
AB  - BACKGROUND/AIMS: Anastomotic leakage after low anterior resection may be the
      result of poor vascular supply from the proximal anastomotic loop. The purpose of
      this study was to investigate the correlation between colonic microvessel density
      and anastomotic breakdown. METHODOLOGY: Between 2006 and 2009, a consecutive
      series of 81 patients underwent double-stapled low anterior resection followed by
      a colorectal anastomosis. Symptomatic anastomotic leakage occurred in 14 patients
      (17%). In these patients, microvascular density was determined by image analysis
      of CD-31-immunostained sections from the proximal resection site. The results
      were compared with a sample of the remaining 67 patients without anastomotic
      leakage closely matched for age, gender, ASA-classification, pathological stage
      and neoadjuvant treatment. RESULTS: The mean percentage of anti-CD31 stained
      area, obtained from the proximal resection site was similar between patients with
      or without anastomotic leakage (4.0% +/- 1.8% versus 4.4% +/- 1.6% respectively,
      P = 0.53). With respect to neo-adjuvant therapy, no differences in the density of
      CD31 positive were observed (pre-operative radiotherapy = 4.3% +/- 1.8% versus
      pre-operative chemoradiotherapy 4.1% +/- 1.6%, P = 0.77). The mean vessel density
      reached borderline statistical significance in women (5.0% +/- 1.8%) compared to
      men (3.8% +/- 1.8%) (P = 0.06). CONCLUSIONS: Microvessel density quantification
      with immunohistochemical analysis of CD31 expression of the proximal anastomotic
      region did not show any correlation with anastomotic leakage in the clinical
      setting.

PMID- 24895799
TI  - Daikenchuto stimulates colonic motility after laparoscopic-assisted colectomy.
AB  - BACKGROUND/AIMS: Paralytic ileus after laparoscopic-assisted surgery often
      occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal
      medicine, improves intestinal motility in patients undergoing laparoscopic
      assisted colectomy for colon cancer. METHODOLOGY: Fifty-four patients who
      underwent colectomy at Iwate Medical University Hospital between October 2010 and
      March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the
      control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints
      included time to first flatus, bowel movement, and tolerance of diet after
      extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level,
      length of hospital stay, and postoperative ileus. Colonic transit time was
      measured using radiopaque markers and abdominal radiographs. RESULTS: Fifty-one
      patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis.
      The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h
      vs. 77.9 +/- 11.8h, P < 0.01) and bowel movement (82.9 +/- 17.8h vs. 99.5 +/-
      18.9h, P < 0.01) and colonic transit time (91.9 +/- 19.8h vs. 115.2 +/- 12.8 h, P
      < 0.05). There were no significant intergroup differences in secondary endpoints
      and adverse events. CONCLUSIONS: DKT accelerates colonic motility in patients
      undergoing laparoscopic-assisted colectomy for colon cancer.

PMID- 24895801
TI  - Survival benefit of oral tegafur/uracil and leucovorin as a first line therapy
      for elderly patients with advanced or metastatic colorectal cancer.
AB  - BACKGROUND/AIMS: This phase II trial was performed to evaluate the efficacy and
      tolerability of tegafur/uracil (UFT) and oral leucovorin (LV) in elderly patients
      with advanced or metastatic colorectal cancer who had not received prior
      chemotherapy. METHODOLOGY: Patients aged > or = 70 years were eligible. UFT and
      LV were taken orally on days 1-28 of the cycle at doses of 300 mg/m2/day and 75
      mg/m2/day, respectively. Treatment was administered on an outpatient basis every
      35 days and consisted of at least two cycles until disease progression. RESULTS:
      A total of 30 patients were enrolled in this study. The median age of the
      patients was 81.5 years (range: 74-88 years). The observed overall response rate
      was 17.9%. The estimated median overall survival time was 23.5 months. Two
      patients (7%) experienced toxicities with a worst grade of 3, and one patient
      (4%) experienced toxicities with a worst grade of 4. There were no treatment
      related deaths. No patients experienced grade 3 or 4 hematological adverse
      events. CONCLUSIONS: Although the response rate to UFT/LV was moderate, a
      favorable survival time was observed. Lower hematological adverse event rate of
      UFT/LV may introduce second line therapy safely to elderly colorectal cancer
      patients and contribute longer survival.

PMID- 24895802
TI  - Phase I trial of preoperative chemoradiation therapy with S-1 for low rectal
      cancer.
AB  - BACKGROUND/AIMS: A phase I study was performed to evaluate the dose-limiting
      toxicity and the recommended dose of the oral fluoropyrimidine S-1 when
      administered concurrently with radiation therapy to 9 Japanese patients with low
      rectal cancer. METHODOLOGY: S-1 was given orally for a total of 9 weeks (4 weeks
      alone and 5 weeks during radiation therapy) at oral doses of 65 mg/m2/day (n = 3
      patients) or 80 mg/m2/day (n = 6 patients). Radiation therapy was administered in
      1.5 gray fractions five times weekly (Monday to Friday) for a total dose of 45
      gray. RESULTS: All patients achieved the planned 45 gray of radiation therapy.
      There was no grade > or = 3 toxicity. The recommended dose of S-1 was determined
      to be 80 mg/m2/ day. The dose intensity of S-1 was well maintained, and the
      combination of S-1 plus radiation therapy was well tolerated by all patients.
      Sphincter-preserving procedures were possible in all but one (89%) patient. High
      rates of tumor shrinkage and nodular downstaging were achieved. The histological
      response rate was 78%, including one complete response. CONCLUSIONS: The
      recommended dose of S-1 with concurrent radiation therapy was 80 mg/m2/day. Pre
      operative chemoradiation therapy with S-1 was feasible and well tolerated by
      patients with low rectal cancer.

PMID- 24895803
TI  - Improvement in the postoperative course of salvage esophagectomy after definitive
      chemoradiotherapy.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the outcome of salvage
      esophagectomy with less extensive lymphadenectomy, which we have performed since
      2003 to improve high mortality and morbidity of standard salvage esophagectomy.
      METHODOLOGY: We retrospectively compared the surgical outcome of 15 patients who
      underwent standard salvage esophagectomy via right thoracotomy for thoracic
      esophageal cancer between 1993 and 2002 (earlier period) with the results of 11
      patients between 2003 and 2011 (later period). RESULTS: There were two
      mortalities in the earlier period, whereas no patient died in the later period,
      and there was a lower rate of morbidity. In the later period, there was a
      significantly shorter SIRS duration, lower CRP on postoperative days 1-5, and
      higher lymphocyte count on postoperative days 2-4. Long-term survival showed no
      significant difference between the two periods. CONCLUSIONS: Salvage
      esophagectomy with less extensive lymphadenectomy might improve the surgical
      outcome while maintaining long-term survival.

PMID- 24895804
TI  - Endoscopic treatment of anastomotic leakage after esophagectomy or gastrectomy
      for carcinoma with self-expanding removable stents.
AB  - BACKGROUND/AIMS: Anastomotic leakage is a feared complication after gastrectomy
      and esophagectomy. We report our experience in the treatment with endoscopic
      stent placement. METHODOLOGY: Seventeen patients with anastomotic leakage after
      resection of a malignant tumor of the stomach or the distal esophagus have been
      long-term followed-up. RESULTS: In 10 patients the implanted stent did
      successfully close the leakage in the first attempt. In 3 out of 7 patients with
      unsuccessfully sealed leakage a stent-in-stent-manoeuvre did successfully seal
      the leakage. We had no major complications upon implantation of the stents. We
      did have no recurrence of a once sealed leakage. CONCLUSIONS: Endoscopic stent
      placement is a safe procedure in the treatment of anastomotic leakage after
      gastrectomy and esophagectomy. It should be performed in any clinically relevant
      leakage if possible. In cases where stent placement is not successful at first,
      correction of position, stent replacement or a stent-in-stent manoeuvre can be
      performed, with promising results.

PMID- 24895805
TI  - The 5-HT4 receptor agonist mosapride attenuates inflammation of reflux
      esophagitis.
AB  - BACKGROUND/AIMS: Chronic inflammatory processes and gastric contents related
      esophageal mucosal injury are two major characteristics of reflux esophagitis
      RE). This study was aimed to establish a rat model fitting RE major
      characteristics and to investigate the effects of mosapride, one of the 5-hydroxy
      tryptamine (5-HT)4 receptor agonists, on mucosal inflammation in RE. METHODOLOGY:
      Rat RE model was established by pyloric clip and section ligation-induced chronic
      acid reflux esophagitis. Animal body weight and survival was monitored. Animals
      were treated with 0.1 mg/kg/d, 0.5 mg/kg/d, or 2.5 mg/kg/d mosapride by gavage.
      Gastric emptying was examined. After two weeks, pathological changes of the
      esophagus were determined and endothelin-1 (ED-1) expression in esophageal
      tissues was evaluated by immunohistochemistry. RESULTS: No significant
      differences were observed in the gastric emptying of RE rats after different
      doses of mosapride treatment (P > 0.05). Gross examination and pathological
      evaluation revealed that either 0.5 mg/kg/d or 2.5 mg/kg/d mosapride treatment
      attenuated the mucosal inflammation of RE, but a lower mosapride dose (0.1
      mg/kg/d) had limited esophagoprotective effects (P > 0.05). Mosapride treatment
      greatly decreased the number of ED-1 positive monocytes in the esophagus compared
      with sham-operated controls (P < 0.05). 5-HT4 receptor and acetylcholine (Ach)
      receptor antagonists effectively reversed the protective effects of mosapride (P
      < 0.05). CONCLUSIONS: Our results demonstrated that mosapride attenuated the
      mucosal inflammation of RE, suggesting that mosapride might provide
      esophagoprotective effects in addition to its well-known prokinetic actions.

PMID- 24895806
TI  - A tandem trial of HD-NBI versus HD-WL to compare neoplasia miss rates in
      esophageal squamous cell carcinoma.
AB  - BACKGROUND/AIMS: To determine whether the use of narrow-band imaging (NBI) system
      could enhance the detection rate of esophageal squamous cell carcinoma and
      precancerous lesions during endoscopic examination of the esophagus. METHODOLOGY:
      113 patients were randomized to undergo endoscopic examination using high
      definition television (HDTV) narrow band imaging (NBI) endoscopy or HDTV WL
      endoscopy. The primary endpoint was the difference in the neoplasm miss rate, and
      secondary outcome was the neoplasm detection rate. RESULTS: The number of
      esophageal cancer and high grade intraepithelial neoplasia lesions detected by HD
      NBI and HD-WL was 45 and 21, respectively. The neoplasm miss rate per lesion and
      per patient with HD-NBI showed significant difference compared with that of HD-WL
      (P <0.05). Characteristics of lesions missed by use of HD-NBI were similar to
      those missed by use of HD-WL; all missed lesions were high grade intraepithelial
      neoplasia lesions. Significant difference was observed between NBI and WL in
      adenoma detection rate (70.2% vs. 35.7%, P < 0.01). CONCLUSIONS: Endoscopy with
      HD-NBI seems to improve the detection of esophageal cancer and precancerous
      lesions, high definition may be tested for its effect on detection of esophageal
      cancer and precancerous lesions in the future. These results indicate that
      endoscopy routinely using the NBI system for the surveillance of esophageal
      cancer and precancerous lesions may be recommended.

PMID- 24895807
TI  - Correlation of 13C urea breath test values with Helicobacter pylori load among
      positive patients.
AB  - BACKGROUND/AIMS: 13C urea breath test (13C UBT) is used to detect Helicbacter
      (H.) pylori in gastric mucosa. There are controversial results regarding
      associations of 13C UBT values with histopathological grades. We designed this
      study to correlate 13C UBT values with different histopathological grades in our
      local setting. METHODOLOGY: 13CO2/12CO2 ratio for 13C UBT was analyzed using mass
      spectrometry and histopatholgical grades were scored by updated Sydney System.
      RESULTS: 13C UBT values of H. pylori positive patients at different times (T10
      T60) were higher as compared to negative patients. Significant positive
      correlation of 13C UBT values at T30 with different scores of H. pylori load (r =
      0.277, p = 0.037) was observed. Associations of the mean 13C UBT values with
      neutrophil infiltration (p = 0.214), mononuclear cell infiltration (p = 0.648),
      atrophy (p= 0.620), atypia (p = 0.057) and metaplasia scores (p = 0.718) were
      found to be nonsignificant. H. pylori load significantly correlated with
      neutrophil infiltration and atrophy with exception of mononuclear cell
      infiltration, atypia and metaplasia. CONCLUSIONS: In the present analysis,
      significant positive correlation was observed between 13C UBT values and H.
      pylori load that would be helpful in qauntification of H. pylori in our local
      setting.

PMID- 24895808
TI  - Clinicopathological characteristics of patients with non-B non-C hepatocellular
      carcinoma: a special reference to metabolic syndrome.
AB  - BACKGROUND/AIMS: This study was carried out to clarify the clinicopathological
      features of hepatocellular carcinoma (HCC) arising in patients without viral
      infection and to confirm the influence of metabolic syndrome (MS) on
      characteristics in HCC patients. METHODOLOGY: Two hundred and thirty-three
      hepatectomized HCC patients were enrolled. The status of the hepatitis viral
      infection was defined; non-B non-C (NBNC) (n = 15), negative for HBs-Ag, HBc-Ab
      or HCV-Ab; HBV (n = 70); HCV (n = 148). We compared clinicopathological features
      and surgical outcomes among three groups. Additionally, fifty-six HCC patients
      who were evaluated on coexistence of MS were divided into two groups and
      analyzed; MS (n = 16) and non-MS (n = 40) groups. RESULTS: In NBNC-patients,
      preoperative platelet counts and ICGR15 were significantly better compared to HCV
      patients (21.8 x 10(4)/mm3 vs. 11.3 x 10(4)/mm3, 14.0% vs. 19.2%, p <0.05). Body
      mass index was significantly higher in NBNC-patients (24.9 vs. 22.4, p < 0.05).
      Overall survival rates were significantly higher in NBNC-patients compared with
      HBV or HCV-patients (5 y: 87.5% vs. 48.8%, 42.9%, p < 0.05). For NBNC-patients
      there were significantly more patients in the MS group than in the non-MS group.
      CONCLUSIONS: HCC with MS included more NBNC-HCC than HBV or HCV related HCC.
      Aggressive hepatectomy contributed to the favorable outcome in NBNC-patients
      because of their better liver function.

PMID- 24895809
TI  - Expression of intestinal tight junction proteins in patients with non-alcoholic
      fatty liver disease.
AB  - BACKGROUND/AIMS: To investigate the expression of tight junction (TJ) proteins
      including Zonula occludens-1 (ZO-1), occludin and claudin-1 in intestinal
      epithelial cells in patients with non-alcoholic fatty liver disease (NAFLD) and
      study its potential association with the pathogenesis of NAFLD. METHODOLOGY:
      Twenty-eight NAFLD patients with elevated transaminase, 30 NAFLD patients with
      normal transaminase and 34 healthy volunteers were enrolled. Their biochemical
      characters were measured and the expression of ZO-1, occludin and claudin-1
      proteins in intestinal epithelial cells was assessed by immunohistochemical
      analysis and its relationship with transaminase levels was also discussed.
      RESULTS: Significant differences were observed on the levels of BMI, TC, TG, FPG,
      ALT, and AST among the three groups. The levels in NAFLD patients with elevated
      transaminase were significantly higher than NAFLD patients with normal
      transaminase and the latter had higher levels than the volunteers. The expression
      of ZO-1 and occludin were significantly different among the three groups (chi2 =
      14.210, p < 0.01; chi2 = 20.543, p < 0.01). The expression of ZO-1 and occludin
      decreased gradually from NAFLD with elevated transaminase to healthy volunteers
      (r = 0.386, p <0.01; r = 0.449, p < 0.01). In NAFLD patients, the levels of the
      expression of ZO-1 and occludin were negatively correlated with the transaminase
      level (r = -0.426, p < 0.01; r = -0.597, p < 0.01). The expression of claudin-1
      was found among all the three groups but no statistical significance was observed
      among three groups (chi2 = 0.686, p = 0.953). CONCLUSIONS: The expression of TJ
      proteins in intestinal epithelial cells are closely related with the occurrence
      and development of NAFLD. The contribution of different TJ protein varies in
      maintaining barrier function.

PMID- 24895810
TI  - Changes of ammonia levels in patients with acute on chronic liver failure treated
      by plasma exchange.
AB  - BACKGROUND/AIMS: Acute on chronic liver failure (AoCLF) is associated with a high
      mortality rate. Plasma exchange (PE) is useful to bridge AoCLF patients to liver
      transplantation. The aim of this study was to assess the effects of PE on plasma
      ammonia levels (PAL) in AoCLF patients. METHODOLOGY: Seventy patients with AoCLF
      in 2 groups (PE plus standard medical treatment group, n = 32; and standard
      medical treatment group, n = 38) were enrolled in study. PAL was detected on
      admission and on days 7, 14, 21, and 30 during hospitalization. RESULTS: All
      AoCLF patients showed PAL more than the upper limit of the normal range. More
      dramatic decreased in the PE survivors (form 116.8 +/- 36.3 to 44.8 +/- 16.3, p <
      0.01) than the medical survivors (form 105.7 +/- 30.2 to 57.1 +/- 20.3, p < 0.05)
      after 30 days of treatment. Furthermore, PAL after medical treatment were still
      higher than those of PE treatment in the survivors (57.1 +/- 20.3 vs. 44.8 +/-
      16.3, p < 0.05). Among the non-survivors in the medical group, PAL remained at
      high levels throughout the examination period. Importantly, an increased PAL
      associated with high mortality and reduced survival time of AoCLF patients.
      CONCLUSIONS: Ammonia may be important in the pathogenesis of the AoCLF and PE may
      represent a reliable hepatic support device for AoCLF.

PMID- 24895811
TI  - Aberrant estrogen receptor alpha expression correlates with hepatocellular
      carcinoma metastasis and its mechanisms.
AB  - BACKGROUND/AIMS: Metastasis one of the obstacles before poor prognosis of
      hepatocellular carcinoma (HCC) is improved. Estrogen receptor alpha (ERalpha)
      plays an important role in the development and progression of HCC. However, the
      molecular mechanism of ERalpha in mediating HCC metastasis is still unclear. The
      aim of the present study was to detect aberrant ERalpha expression in HCC and
      elucidate its possible mechanisms in HCC metastasis. METHODOLOGY: We detected
      expression of ERalpha, phospho-estrogen receptor alpha (p-ERalpha), nuclear
      factor kappa B (NF-kappaB) p65 and Matrix metalloproteinase-9 (MMP-9) between HCC
      tissues with portal vein tumor thrombus (PVTT) and those without PVTT by
      immunohistochemical method. Moreover, the expression of above parameters was also
      determined in HCC cells of different metastatic potential by using
      immunocytochemical and reverse transcriptase-polymerase chain reaction (RT-PCR)
      methods. RESULTS: The expression of ERalpha and p-ERalpha was lower in HCC with
      PVTT than those without PVTT. Meanwhile, the expression pattern of above
      parameters was also similar in HCC cells of different metastatic potential,
      whereas, the expression of NF-kappaB p65 and MMP-9 was higher in HCC with PVTT
      than those without PVTT. The expression of NF-kappaB p65 and MMP-9 in HCC cells
      was also analogous to the tissues. CONCLUSIONS: These results demonstrated that
      expression of ERalpha, p-ERalpha, NF-kappaB p65 and MMP-9 correlated with
      invasion and metastasis in HCC. The mechanism of HCC metastasis may mediate
      through cross-talk between the NF-KB and ER signaling pathways. Meanwhile, ERa
      regulated MMP-9 through NF-kappaB indirectly.

PMID- 24895812
TI  - Hepatic arterial infusion chemotherapy combined with endogenetic hyperthermia
      treatment of hilar cholangiocarcinoma.
AB  - BACKGROUND/AIMS: To evaluate the curative effect and clinical application of
      hepatic arterial infusion (HAI) chemotherapy combined with endogenetic field
      tumor hyperthermia (EFTH) in patients with hilar cholangiocarcinoma. METHODOLOGY:
      Nine patients with unresectable hilar cholangiocarcinoma were enrolled. They were
      first treated with HAI using gemcitabine, and then carboplatin was continuously
      infused intra-arterially whereas EFTH was applied to the hilar region for 60 min.
      After hyperthermia, 5-fluorouracil was administered intra-arterially for three
      days. The same dose of gemcitabine was administered intravenously on Day 8. The
      side effects, tumor markers, tumor response and overall survival (OS) were
      observed and assessed. RESULTS: Nine patients underwent 27 cycles of the
      combination therapy. Of the nine patients, five patients achieved complete
      remission and they are still alive, and four died. Of the four patients who died,
      two achieved partial remission, one had stable disease, and one had progressive
      disease. The tumor markers decreased at varied degrees among the seven patients.
      The overall response rate was 77.78% (7/9), and the disease control rate was
      88.89% (8/9). The treatment had no severe side effects and complications,
      including grade 3/4 hematological toxicities. CONCLUSIONS: HAI chemotherapy
      combined with EFTH is safe, minimally invasive, and well tolerated.

PMID- 24895813
TI  - Autologous stem cell transplantation for expansion of remnant liver volume with
      extensive hepatectomy.
AB  - BACKGROUND/AIMS: The plasticity of bone marrow stem cells has been confirmed to
      self-renew and transdifferentiate into hepatocytes. Thus, we performed autologous
      stem cell transplantation for rapid liver regeneration with extensive hepatectomy
      in hepatocellular cancer patients. METHODOLOGY: With informed consent, patients
      aged 20 to 75 who needed large extensive hepatectomy due to hepatocellular
      carcinoma were randomly divided into three groups: control, mononuclear cells
      (MNCs), and CD34+ cells, based on infused cell type. After portal vein
      embolization (PVE), mobilized MNCs or CD34+ cells were returned to the patient
      via the portal vein on mobilization day without manipulation. Liver volume, liver
      function, clinical score and Indocyanine green R15 (ICG-R15) were compared before
      and after PVE. RESULTS: Total bilirubin, albumin, and clinical score showed
      significant improvement (p < 0.05) 1 week post-infusion, with no significant
      difference between MNC and CD34+ cell groups. Four patients (control, 1; MNC, 1;
      CD34+, 2) started at over 18% ICG-R15 but can be overturned after PVE. Daily
      hepatic volume growth (mL/day) was 2.5 for MNC and 4.9 for CD34+ groups,
      resulting in significant increase over controls (1.1; p < 0.05). We found no
      correlation between the number of applied CD34+ cells and daily gains in left
      lateral lobe volume. CONCLUSIONS: Improvements in liver volume, liver function,
      clinical score and ICG-R15 suggest that autologous stem cell transplantation is a
      promising method for liver regeneration.

PMID- 24895814
TI  - Systemic gemcitabine combined with hepatic arterial infusion chemotherapy with
      cisplatin, 5-fluorouracil, and isovorin for the treatment of advanced
      intrahepatic cholangiocarcinoma: a pilot study.
AB  - BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and
      usually presents as advanced disease. Hepatic arterial infusion chemotherapy
      (HAIC) is a promising option for advanced hepatocellular carcinoma; however,
      there have been few reports on the use of HAIC in patients with ICC. In the
      present study, we investigated the efficacy of treatment with systemic
      gemcitabine (GEM) combined with HAIC with cisplatin (CDDP), 5-fluorouracil (5
      FU), and isovorin in patients with advanced ICC. METHODOLOGY: Seven patients with
      advanced ICC, who received systemic GEM combined with HAIC with CDDP, 5-FU, and
      isovorin were studied. RESULTS: The response rate after the first chemotherapy
      cycle was 57.1% (partial response, 4; stable disease, 2; progressive disease, 1).
      The cumulative survival rates at 1 and 2 years were 85.7% and 28.6%,
      respectively, and the median survival time was 22.3 months. With regard to grade
      3 or 4 adverse reactions, the percentages of patients developing leukopenia,
      neutropenia, thrombocytopenia, anemia, and anorexia were 28.6%, 28.6%, 42.9%,
      14.3%, and 14.3%, respectively. Na treatment-related deaths were encountered.
      CONCLUSIONS: Although this is a pilot study, we suggest that systemic GEM
      combined with HAIC with CDDP, 5-FU, and isovorin, may be a useful therapy for
      patients with advanced ICC.

PMID- 24895815
TI  - Fast-track surgery improves postoperative outcomes after hepatectomy.
AB  - Fast-track (FT) programs have been applied in colorectal surgery for years. But
      in liver surgery, role of FT programs has not been fully established. So, a
      perspective study was performed in our center. A total of 297 hepatocellular
      carcinoma patients were randomized into FT and non-FT (NFT) group (n = 135 and
      162, respectively) according to perioperative managements. Operation time,
      anhepatic phase and intraoperative blood loss were all significantly reduced in
      FT group; besides, first exhaust time after operation and hospital stay were also
      shortened significantly. Spearman correlation showed that operation time was
      positively correlated with four parameters, including the anhepatic phase, the
      intraoperative blood loss during surgery, the hospital day and the first exhaust
      time after surgery. The anhepatic phase was also positively correlated with the
      intraoperative blood loss during surgery. Besides, the hospital day was
      positively correlated with the intraoperative blood loss during surgery and the
      first exhaust time after surgery. FT postoperative management was the only
      predictor of the shorter first exhaust time after operation and the shorter
      hospital day. No total postoperative complication, readmission and postoperative
      mortality were observed. Our data indicated that FT programs were safe and
      effective in hepatectomy.

PMID- 24895816
TI  - Hepatic resection for multiple hepatocellular carcinoma less than 5 cm: a
      prospective comparative study.
AB  - BACKGROUND/AIMS: Treatment of multiple hepatocellular carcinoma (HCC) remains a
      critical issue. In addition, the prognosis and prognostic factors of multiple HCC
      after hepatic resection are rarely prospectively documented. METHODOLOGY: The
      clinicopathologic and follow-up data of 81 patients who underwent curative
      resection of HCC between January 2008 and January 2009 were prospectively
      collected. Patients were categorized according to the size of the largest tumor:
      group A (n = 40, two or three HCCs with maximum tumor diameter > 3 cm and < or =
      5 cm) and group B (n = 41, two or three HCCs with maximum tumor diameter < or = 3
      cm). The two groups were compared for clinicopathologic data and survival
      results. RESULTS: The 1-, 2-, 3-, and 4-year survival rates of group A were
      75.0%, 58.0%, 50.0%, and 44.0%, respectively, while the survival rates of group B
      were 93.0%, 80.0%, 66.0%, and 47.0%, respectively. The 1-, 2-, 3-, and 4-year
      disease-free survival rates of group A were 43.0%, 30.0%, 23.0%, and 15.0%,
      respectively, comparing to 71.0%, 54.0%, 44.0%, and 36.0% in group B,
      respectively. The median overall cumulative survival time of group A and group B
      were 36.0 and 44.5 months, respectively (P = 0.322). The median disease-free
      survival time of group A was 10.0 months and was significantly shorter than that
      of group B (30.0 months, P = 0.011). CONCLUSIONS: Resection may provide
      comparative survival benefits even for patients with multiple HCCs with maximum
      tumor diameter > 3 cm and < or = 5 cm.

PMID- 24895817
TI  - Is there a role for surgical resections of hepatic breast cancer metastases?
AB  - Breast cancer accounts for over 12,000 deaths in the UK annually; 12% of women
      develop hepatic metastases receiving systemic therapy as standard treatment.
      Hepatic resection has been proposed as a potentially curative alternative.
      Current literature was reviewed and evaluated for hepatic resection on breast
      cancer liver metastases by conducting a literature search across Ovid Medline,
      Embase and PubMed. Twenty-one studies were included in the review. All were
      retrospective, single centre case series. Eighteen studies reported results for
      ten or more patients. Only three studies reported results for over 50 patients.
      The time-span for the individual series ranged from 9-20 years. Generally, liver
      resection for breast cancer liver metastases is a safe procedure with only two
      post-operative deaths reported. Median time to recurrence was low (10-36 months).
      Overall 5-year survival ranged from 12-75%. Poorer prognosis correlated with
      increasing size and number of metastases, extrahepatic spread and short time span
      from primary surgery to the development of further metastases. Current literature
      does not establish clearly, who should undergo a hepatic resection for breast
      cancer metastasis. But it seems that hepatic resection should be considered as a
      therapeutic option for limited volume liver metastasis in high-risk breast cancer
      patients. However, prospective cohort studies are required to establish the role
      of hepatic resection for breast cancer metastasis.

PMID- 24895818
TI  - Survival differences between Milan criteria after down-staging and De novo Milan
      in living donor liver transplantation for hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: This study reports our experiences of adult living donor liver
      transplantation (LDLT) corresponding to downstaging. METHODOLOGY: Between July
      1992 and April 2008, we performed 553 adult LDLTs (35.1%, 553/1575) for HCC.
      Sixty-five patients was not treated before LDLT and belonged to Milan criteria,
      classified as De novo Milan group (De novo-M); 22 HCC patients did not meet Milan
      criteria initially, but subsequently met the criteria after downstaging,
      classified as artificial Milan group (Artificial-M). The evaluation of
      downstaging was based on preoperative CT scan and explanted liver biopsy, and
      excluded the patients having unclear treatment history on analysis. RESULTS:
      Artificial-M showed significantly less Child C patients (25%) than De novo-M
      (64.5%) (0.037). Artificial-M had greater tumor burden than De novo-M in maximal
      tumor size (2.5 +/- 1.2 versus 2.2 +/- 0.95 cm), sum of tumor diameter (3.4 +/-
      1.4 versus 2.4 +/- 1.0 cm), number of nodules (1.8 +/- 0.9 versus 1.2 +/- 0.5),
      respectively. Five-year cumulative survival was not different between Artificial
      M and De novo-M (83.9% versus 93.9%), but 5-year disease free survival were
      significantly different (71.1% versus 96.5%) (p = 0.0016). CONCLUSIONS: Five year
      overall survival rates after LDLT were good in both groups. However, stricter
      follow-up is necessary in Artificial-M considering greater tumor burden and
      higher recurrence rate compared to De novo-M.

PMID- 24895819
TI  - The role of cryosurgery in the treatment of colorectal liver metastases: a
      matched-pair analysis of cryotherapy vs. liver resection.
AB  - BACKGROUND/AIMS: Although liver resection is the gold standard for patients with
      colorectal liver metastases (CRLM), only 15-20% of the patients are candidates
      for surgery. As ablative therapies may extend this low rate of curative option,
      the aim of the present study was to analyze the impact of cryosurgery (cryo) on
      survival of patients with CRLM compared to liver resection (Phx). METHODOLOGY: In
      a matched-pair analysis, patients undergoing Phx or cryo were compared (n = 39
      each). Analysis included pre-, peri-and postoperative data and follow-up for
      tumor-free and overall survival. Survival was estimated by Kaplan-Meier method.
      RESULTS: Out of 124 patients undergoing 143 cryosurgical procedures, 39 patients
      could be identified undergoing single liver cryo procedure for CRLM with a
      curative approach. Matching of these patients with a Phx cohort, patients
      undergoing Phx revealed better overall (20 vs. 46 months) and tumor-free survival
      (7.8 vs. 33.6 months) than patients with cryo. CONCLUSIONS: Liver resection is
      strongly recommended for patients with CRLM compared to cryosurgery.

PMID- 24895820
TI  - Hepaticocholecystojejunostomy as effective palliative biliary bypass for
      unresectable pancreatic cancer.
AB  - BACKGROUND/AIMS: The majority of patients with pancreatic cancer present with far
      advanced disease and jaundice. With the advancement of endoscopic interventional
      techniques, the role of surgical bypass has declined. However, surgical bypass is
      still considered to be appropriate in patients who are able to tolerate surgery.
      We performed hepaticocholecystojejunostomy consecutively as a palliative surgical
      biliary bypass for the purpose of long-term palliation. The aim of this study was
      to analyze the results of our palliative surgical biliary bypass,
      hepaticocholecystojejunostomy. METHODOLOGY: Between January 2001 through December
      2009, 69 patients received palliative surgical biliary bypass (bypass group) and
      33 patients received endoscopic biliary stenting (stent group) for unresectable
      pancreatic cancers. Mortality, morbidity and survival between the two groups were
      compared. RESULTS: There was no in-hospital death in the bypass group, but 2
      patients (6%) in the stent group died in the hospital (p = 0.04). The surgical
      morbidity rate was 15% in the bypass group, while 20 patients (61%) in the stent
      group developed complications, mainly due to stent blockage. There was no
      significant difference in overall survival between the two groups. Among patients
      who underwent systemic chemotherapy but did not present with jaundice at the time
      of diagnosis, those who underwent prophylactic surgical biliary bypass before
      chemotherapy showed better survival than those who underwent systemic
      chemotherapy preceding biliary bypass or biliary stenting after occurrence of
      jaundice (p = 0.01). CONCLUSIONS: Hepaticocholecystojejunostomy resulted in
      negligible mortality, low morbidity and effective long-term palliation.
      Prophylactic surgical biliary bypass with gastrointestinal bypass might be a good
      treatment option for non-jaundiced patients undergoing chemotherapy for
      unresectable pancreatic cancer.

PMID- 24895821
TI  - Instruction of expert surgeon secures favorable outcomes after standard
      pancreaticoduodenectomy performed by less experienced surgeons.
AB  - BACKGROUND/AIMS: We investigated the factors associated with a favorable outcome
      after standard pancreaticoduodenectomy (PD) performed by the less experienced
      surgeon under expert supervision in a high-volume hospital of PD. METHODOLOGY:
      Between April 2009 and March 2013, 139 PDs were performed in our hospital, and
      among them 99 PDs were standard fashion. Two expert surgeons performed 57 of 99
      PDs, and the cases were assigned as Group A. Forty-two of 99 PDs were performed
      by 5 less experienced surgeons under the instruction of expert surgeons, and the
      cases were assigned as Group B. We compared the intraoperative outcomes and
      postoperative major complications and mortality between two groups. RESULTS:
      There was no hospital death in Group B, but one in Group A (1.8%), and the
      overall mortality rate of 99 patients in this series was 1.0%. In comparison of
      postoperative major complications, there was no significant difference in the
      frequencies of patients with all postoperative major complications (Group A;
      43.9% vs. Group B 33.3%). CONCLUSIONS: Outcomes after standard PD performed by
      less experienced surgeons were favorable. The instruction of expert surgeon in a
      high volume hospital may secure a favorable outcome after standard PD.

PMID- 24895822
TI  - Interleukin-12 as a predictor of outcome in patients with severe acute
      pancreatitis.
AB  - BACKGROUND/AIMS: The aim of this study was to determine the role of serum
      Interleukin-12 level as early marker of severity of the SAP and correlation
      between IL12, SIRS score, APACHE II and Ranson score in prediction of illness
      severity as well as of outcome of SAP. METHODOLOGY: We evaluated a total of 234
      patients with first onset of SAP, appears in last 24 hours, admitted in surgical
      Intensive care unit (ICU). Severe Acute Pancreatitis was diagnosed with an APACHE
      II score of 8 or higher, and/or a Ranson score of 3 or higher, and/or Balthazar
      scores of 5 or higher. Serum IL-12 concentrations were measured with a
      commercially aviable IL-12 kit, on admission and days 3, 7, and 14. RESULTS: IL
      12 concentration was significantly higher at 24h compared with IL-12 levels at
      admission (P = 0.010) and after 72h (P = 0.005). IL-12 concentrations
      significantly correlated with IL-6 concentrations (r = 0.209, P < 0.001), IL-8
      concentrations (r = 0.527, P < 0.001), IL-10 concentrations (r = 0.552, P <
      0.001), interpheron-gamma (r = 0.740, P < 0.001), TNF-alpha (r = 0.088, P <
      0.05), C-reactive protein (r = -0.097, P < 0.001), in-hospital death (r = -0.171,
      P < 0.001), APACHE II score (r = 0.140, P < 0.001), and Ranson score (r = -0.319,
      P < 0.001). CONCLUSIONS: The serum values of the IL-12 can be used as an early
      marker of severity and course of SAP.

PMID- 24895823
TI  - Single-incision laparoscopic distal pancreatectomy: our initial experience.
AB  - BACKGROUND/AIMS: Single-incision laparoscopic surgery (SILS) is gaining
      popularity as a minimally invasive surgery. However, SILS distal pancreatectomy
      (SILS-DP) remains a challenging surgical procedure. In this study, we describe
      our initial experience with five cases of SILS-DP. METHODOLOGY: We present an
      initial series of SILS-DP, performed between August 2010 and January 2013.
      RESULTS: Five patients successfully underwent SILS-DP. The median operative time
      was 264 min (range, 232-345 min). The median intraoperative blood loss was 71 cc
      (range, 5-200 cc). All the patients left the hospital in good condition after
      SILS-DP. CONCLUSIONS: Although SILS-DP is a safe, feasible, and esthetic
      procedure, a randomized controlled study is required to determine the advantages
      of SILS-DP in comparison with the standard laparoscopic method.

PMID- 24895824
TI  - Interleukin-6, interleukin-8 and interleukin-10 in estimating the severity of
      acute pancreatitis: an updated meta-analysis.
AB  - BACKGROUND/AIMS: Early identification of severe AP can decrease the mortality
      rate and complications of SAP. The performance of IL-6 and IL-8 and IL-10 can act
      as markers of the severity of acute pancreatitis. Therefore, we aimed to evaluate
      the accuracy of IL-6, IL-8 and IL-10 in estimating the severity of acute
      pancreatitis. METHODOLOGY: MEDLINE and PubMed were searched from Jan 1990 to Nov
      2012 for relevant studies. We calculated pooled sensitivities and specificities
      using the Dersimonian-Laird random-effect methods and generate the summary
      receiver operating curve and area under the curve was reported. RESULTS: Twelve
      studies were eligible; 9 reports including 462 patients assessed the accuracy of
      IL-6 on day 1 of hospital admission, 5 reports including 208 patients on day 2,
      and 5 reports including 188 patients on day 3. Five studies (n = 299 patients)
      assessed the accuracy of IL-8 on day 1, and 4 (n = 182 patients) on day 2. They
      are 4 studies including 284 patients of IL-10 on day 1. CONCLUSIONS: IL-6, IL-8,
      and IL-10 may be the predictive markers of SAP. But the best cut-off values and
      the controversial results of different research may be the largest problem.
      Therefore, multi-center research and large samples should be done to solve the
      present problem.

PMID- 24895825
TI  - Clinicopathological features of CA19-9-producing gastric cancer.
AB  - BACKGROUND/AIMS: The aims of this study were to define CA19-9-producing gastric
      cancer and investigate its clinicopathological features. METHODOLOGY: Twenty
      three patients showing high preoperative serum CA19-9 levels (> or = 38 U/mL)
      were enrolled in this retrospective cohort study. The CA19-9 cut-off level was
      determined on the basis of receiver operating characteristic analysis of CA19-9
      levels obtained from patients having survived for 3 years after surgery. Patients
      in whom the CA19-9 level was the cut-off level or higher were defined as having
      CA19-9-producing gastric cancer (Group A), and their clinicopathological features
      were compared with those of patients showing CA19-9 levels less than the cut-off
      level (Group B). RESULTS: The preoperative serum CA19-9 cut-off level was set at
      77 U/mL. In Group A, lymph node metastasis was seen in all 11 patients, with the
      incidence being higher than that in Group B (p <0.001). The number of patients
      with stage III or greater disease was 10 in Group A, compared with only 3 in
      Group B (p < 0.001). The independent prognostic factors were preoperative serum
      CA19-9 levels, venous invasion and tumor stage. CONCLUSIONS: CA19-9-producing
      gastric cancer is a type of gastric cancer with poor prognosis and characterized
      by preoperative serum CA19-9 > or = 77 U/mL.

PMID- 24895826
TI  - Multi locus sequence typing (MLST) used as a tool to confirm the ability of
      susceptible Helicobacter pylori strains to gain resistance to clarithromycin
      during eradication therapy.
AB  - BACKGROUND/AIMS: Primary resistance of H. pylori to clarithromycin is the most
      common reason for eradication failure, followed by mixed susceptible/ resistant
      H. pylori strain infection. To distinguish between mixed infections and H. pylori
      switch to resistance phenotype during eradication therapy, we proceeded with
      multi locus sequence typing (MLST) of H. pylori strains isolated from gastric
      biopsy samples of patients before and after eradication therapy. METHODOLOGY: We
      collected H. pylori isolates from gastric biopsies from 133 patients who were
      never treated for H. pylori. Five patients had eradication failure with the first
      isolate susceptible and second isolate resistant to clarithromycin. To analyse
      genotypes of first and second H. pylori isolates, we compared H. pylori strain
      sequences of 7 housekeeping genes with MLST. RESULTS: Five patients had
      clarithromycin-sensitive H. pylori before eradication therapy and gained H.
      pylori-resistant to clarithromycin after eradication therapy. The sensitive and
      resistant colonies of each of the H. pylori populations, taken from patients
      before/after antibiotic therapy, had identical sequence types (ST) obtained with
      MLST. CONCLUSIONS: The factors favouring H. pylori survival and switch to
      antibiotic-resistance during eradication therapy probably enable milder
      environmental conditions for H. pylori persistence during therapy. One of such
      factor is the ineffective destruction of mucosa-adhered H. pylori by immune cells
      during therapy which may be due to locally induced immune deficit by H. pylori
      molecules like strain specific H. pylori lipopolysaccharides.

PMID- 24895827
TI  - The selection of surgical treatment for gastric cancer patients with cirrhosis
      and hypersplenism.
AB  - BACKGROUND/AIMS: This study is to find the changes of hypersplenism, the
      leukocyte, platelets count, blood loss and operative time, hospitalization days
      in gastric cancer patients with cirrhosis and hypersplenism after splenectomy or
      splenic artery ligation. METHODOLOGY: 32 gastric cancer patients with cirrhosis
      and hypersplenism were divided into two groups performed radical gastrectomy
      combined with splenectomy (Group A, n = 17) or splenic artery ligation (Group B,
      n = 15), 16 gastric cancer patients performed radical gastrectomy were selected
      as control group (Group C). Then, statistical analyzed. RESULTS: There were no
      significant differences of the leukocyteand platelets between Group A and B (p >
      0.05), but significant compared with Group C (p < 0.01). After 6 chemotherapy,
      the differences of the leukocyteand platelets were obvious between Group A and C
      (p < 0.05), but not between Group B and C (p > 0.05). There were significant
      differences on the grading of hyperhepatia between Group A and B. Except the
      operative time of Group B and C (p > 0.05), there were significant differences on
      the blood loss, the operative time and hospitalization days among three groups (p
      < 0.05). CONCLUSIONS: The splenic artery ligation method was much more rational
      than splenectomy and it was preferred for the gastric cancer patients with
      cirrhosis and hypersplenism.

PMID- 24895828
TI  - Gastroduodenal pathology in patients with asymptomatic gallbladder stones.
AB  - BACKGROUND/AIMS: Gallbladder stones are still a common pathology worldwide, and
      the number of patients diagnosed without any symptoms is increasing due to the
      use of ultrasound and imaging tools such as CT and MRI. The aim of this study was
      to identify gastroduodenal pathologies in patients with diagnosed asymptomatic
      gallbladder stones, since some cases of epigastric pain may have led to
      unnecessary cholecystectomies. METHODOLOGY: Gastroscopic investigations were
      performed in 33 patients diagnosed with asymptomatic gallbladder stones during a
      gallstone screening program in Chiang Mai, Thailand, and followed-up with yearly
      ultrasound examinations. The mean age of the patients was 56.6 years, and mean
      follow-up time was 2.3 years. RESULTS: Our results showed that inflammatory-based
      gastroduodenal lesions in this group were common (15/33 patients, 45.4%). Lesions
      included gastric ulcers (1 patient, 3%), duodenal ulcers (5 patients, 15.1%), and
      gastroduodenal ulcers (2 patients, 6.1%). Almost all of the ulcers were in the
      healing or scarring stage. Inflammatory-based mucosal changes were also detected
      in these patients as follows: erosive gastritis (6 patients, 18.2%) and
      hemorrhagic gastritis (1 patient, 3%). CONCLUSIONS: Inflammatory-based
      gastroduodenal pathologies such as peptic ulcers and gastritis are common in
      patients with asymptomatic gallstones. If such patients become symptomatic,
      meticulous examinations are needed to avoid unnecessary cholecystectomies and
      resulting complications such as postcholecystectomy syndrome. The theory that
      gastroduodenal lesions occur after gallbladder removal needs to be re-evaluated
      given that lesions can be detected before surgery and even before the occurrence
      of symptoms.

PMID- 24895829
TI  - Usefulness of the TRC method in the peritoneal washing cytology for gastric
      cancer.
AB  - BACKGROUND: Peritoneal dissemination from gastric cancer is the most frequent
      metastasis of advanced gastric cancer. Detection of cancer micrometastasis is
      required for improvement of cancer therapy. A method that can detect
      micrometastases more sensitively is desired. Against this background, for the
      purposes of making the genetic diagnosis of micrometastasis simple and rapid, TRC
      (transcription reverse transcription concerted reaction) was developed.
      METHODOLOGY: 69 patients with gastric cancer in those diagnosed with deeper than
      mp. At the time of surgery, peritoneal washing with saline was extracted. Having
      extracted the RNA therein, It was blended with a reagent responsive to CEAmRNA
      and was put into TRC. The cytology and TRC were compared and studied. RESULTS:
      The concordance rate between TRC and cytology was K=0.6552. The patients whom
      there was a discrepancy between the cytology and TRC are clinically validate the
      TRC results. In the study of prognosis, TRC obtained a sensitivity of 90.9% and a
      specificity of 98.3%. CONCLUSION: The measurement of CEAmRNA in peritoneal
      washing specimens by the TRC method is superior to Cytology. That is also equal
      to or superior to the RT-PCR method with respect to sensitivity and specificity,
      and superior with respect to simplicity and rapidity.

PMID- 24895830
TI  - High expression of transform growth factor beta 1 in gastric cancer confers worse
      outcome: results of a cohort study on 184 patients.
AB  - BACKGROUND/AIMS: Transform growth factors beta (TGFbeta) plays different roles at
      different stages of tumor development. TGFbeta1 is one isoform of TGFbeta, with
      complex secretion mechanism and bidirectional functions. This study was to
      investigate TGFbeta1 expression and its clinical significance in different
      clinicopathological subgroups of gastric cancer (GC) patients. METHODOLOGY: Tumor
      and peritumoral tissues from 184 GC patients were constructed into three tumor
      tissue microarrays. The expression of TGFbeta1 was analyzed by
      immunohistochemistry methods. RESULTS: TGFbeta1 was mainly expressed in the
      cytoplasm and membrane of GC cells. Low TGFbeta1 expression was observed in 82
      (44.6%) tumor and 28 (68.3%) peritumoral tissues, and high expression was
      observed in 102 (55.4%) tumor and 13 (31.7%) peritumoral tissues. TGFbeta1
      expression was significantly higher in tumor than peritumoral tissues (chi2 =
      7.554, P = 0.006). The high expression of TGFbeta1 was related to worse overall
      survival (OS) (P = 0.040). TGFbeta1 expression was higher in the old and
      intestinal type GC than in the young (P = 0.017) and in diffuse type GC (P =
      0.015), respectively. Patients with high TGFbeta1 expression had a worse survival
      in young people, female, diffuse type GC, poor differentiation, and lymph nodes
      metastasis. Multivariate Cox proportional hazards analysis showed that age,
      pathological grading, serosal invasion and TGFbeta1 expression were independent
      risk factors. CONCLUSIONS: High TGFbeta1 expression may indicate poor prognosis
      of GC patients and warrant more active treatment against TGFbeta1.

PMID- 24895832
TI  - Clinical significance in combined detection of serum pepsinogen I, pepsinogen II
      and carbohydrate antigen 242 in gastric cancer.
AB  - BACKGROUND/AIMS: To explore the diagnosis value and clinical significance of
      combined detection of serum pepsinogen I (PG I), pepsinogen II (PG II), PG I/II
      and CA242 in patients with stomach diseases. METHODOLOGY: Serum PG I, PG II and
      CA242 were detected with time-resolved fluoroimmunoassay (TRFIA) method. Serum
      levers of the four markers in gastric carcinoma were compared with that in
      chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer and
      normal controls. The four indices were analyzed to judge their diagnosis value
      and the relationship with the biology behavior of gastric carcinoma. RESULTS: The
      serum concentration of PG I in gastric carcinoma and in chronic atrophic
      gastritis were remarkably lower than that in controls (P < 0.05). The serum
      concentration of CA242 in gastric carcinoma was significantly higher than that in
      controls (P < 0.05). CONCLUSIONS: To detect the levers of serum PG I, PG II, PG
      I/II would help to judge the metastasis and prognosis of gastric carcinoma.
      Combined detection of the four indices could increase the positive rate of
      diagnosis in gastric carcinoma.

PMID- 24895831
TI  - Pathological findings of gastric mucosa in patients with gastric remnant cancer.
AB  - BACKGROUND/AIMS: The mechanism of remnant gastric cancer development has not yet
      been well established. In this study, we compared the background gastric mucosa
      of remnant gastric cancer with that of upper lesion-restricted gastric cancer to
      determine the difference in the pathogenesis of naive gastric cancer and remnant
      gastric cancer. METHODOLOGY: Twenty-five patients with gastric remnant cancer
      after distal gastrectomy and a control group of 29 patients with naive gastric
      cancer restricted to the upper part of the stomach who underwent gastrectomy were
      enrolled in this study. We evaluated the gastric mucosa adjacent to cancerous
      tissues using the updated Sydney score system. RESULTS: The surrounding gastric
      mucosa in the remnant gastric cancer group was significantly less atrophic than
      that of the group with gastric cancer restricted to the upper part of the
      stomach. In remnant gastric cancer, patients who underwent Billroth II (B-II)
      reconstruction at first gastrectomy developed cancer at the anastomotic site more
      frequently than those with Billroth I (B-I) reconstruction. CONCLUSIONS: The
      surrounding gastric mucosa was significantly less atrophic in remnant gastric
      cancer than naive gastric cancer, which indicates that remnant gastric cancer
      might possess a different pathogenesis.

PMID- 24895833
TI  - Analysis of resected gastric cancer in Turkish population.
AB  - BACKGROUND/AIMS: Gastric cancer is still an important health issue in Eastern
      Europe and Middle East, including Turkey, although its prevalence is decreasing
      in the western world. METHODOLOGY: In order to define the profiles of the
      patients operated with a diagnosis of gastric cancer in Turkey, a multicenter
      retrospective study was conducted. RESULTS: Six hundred and forty-eight of the
      840 patients with complete data in all parameters were included in the analysis.
      The median follow-up time was 17.16 months (range, 6-143.63 months). Mean age was
      57 +/- 11.7 (19-85). There was a recurrent disease in 42% of the tumors located
      at cardia, corpus or antrum, and 86% of diffuse tumors (p < 0.0001). The ratio of
      patients with recurrent disease was greater in stage III and IV tumors There were
      also greater recurrence ratios in patients with node positive (pN1-3) patients
      than pN0 tumors, and pT3-4 tumors than pT1 or pT2 tumors. Any recurrence was
      found in 48% of the tumors with lymphovascular invasion, while in 39% without
      lymphovascular invasion (p = 0.026). A statistically significant difference was
      found in the recurrence status of patients with positive/dissected node ratio of
      < 10% and > or = 10% (p < 0.0001). CONCLUSIONS: Gastric cancer cases in Turkey
      are seen at a younger age, and at a higher stage. Proximal gastric cancer is seen
      much less than the western series. Prognostic significance of lymphovascular
      invasion in both univariate, and multivariate analyses is noteworthy.

PMID- 24895834
TI  - Electrochemistry of graphene and related materials.

PMID- 24895835
TI  - Cellular membrane enrichment of self-assembling D-peptides for cell surface
      engineering.
AB  - We occasionally found that several self-assembling peptides containing D-amino
      acids would be preferentially enriched in cellular membranes at self-assembled
      stages while distributed evenly in the cytoplasma of cells at unassembled stages.
      Self-assembling peptides containing only Lamino acids distributed evenly in
      cytoplasma of cells at both self-assembled and unassembled stages. The self
      assembling peptides containing D-amino acids could therefore be applied for
      engineering cell surface with peptides. More importantly, by integrating a
      protein binding peptide (a PDZ domain binding hexapeptide of WRESAI) with the
      self-assembling peptide containing D-amino acids, protein could also be
      introduced to the cell surface. This study not only provided a novel approach to
      engineer cell surface, but also highlighted the unusual properties and potential
      applications of self-assembling peptides containing D-amino acids in regenerative
      medicine, drug delivery, and tissue engineering.

PMID- 24895837
TI  - Heterometallic 3d-4f coordination polymers based on 1,4,7-triazacyclononane-1,4,7
      triyl-tris(methylenephosphonate).
AB  - Five heterometallic 3d-4f coordination polymers based on 1,4,7-triazacyclononane
      1,4,7-triyl-tris(methylenephosphonic acid) (notpH6) are reported. Compounds
      [FeLn(notpH)(H2O)4]ClO4.5H2O [Ln = Nd (FeNd), Gd (FeGd), Sm (FeSm), Eu (FeEu)]
      are isostructural. All show layer structures in which the Fe(notpH)(2-) unit
      serves as a metalloligand to link four equivalent Ln(III) ions into a layer.
      Compound [CuLa(notpH2)(H2O)2]ClO4.3H2O (CuLa) displays a chain structure, where
      the Cu(notpH2)(2-) unit connects the La(III) ions into a chain. The magnetic
      properties of FeLn are studied. 

PMID- 24895836
TI  - Diastereoselective total synthesis of salvileucalin C.
AB  - A concise and efficient approach for the diastereoselective total synthesis of
      salvileucalin C, as well as their biosynthetically related diterpenoids
      salvileucalin D, salvipuberulin, isosalvipuberulin, and dugesin B, has been
      reported for the first time. The key features of the strategy are based on a
      Beckwith-Dowd ring expansion, a tandem diastereoselective Stille
      coupling/debromination/desilylation/lactonization reaction, and a photoinduced
      electrocyclic ring contraction. 

PMID- 24895838
TI  - Additive-free hollow-structured Co3O4 nanoparticle Li-ion battery: the origins of
      irreversible capacity loss.
AB  - Origins of the irreversible capacity loss were addressed through probing changes
      in the electronic and structural properties of hollow-structured Co3O4
      nanoparticles (NPs) during lithiation and delithiation using electrochemical
      Co3O4 transistor devices that function as a Co3O4 Li-ion battery. Additive-free
      Co3O4 NPs were assembled into a Li-ion battery, allowing us to isolate and
      explore the effects of the Co and Li2O formation/decomposition conversion
      reactions on the electrical and structural degradation within Co3O4 NP films. NP
      films ranging between a single monolayer and multilayered film hundreds of
      nanometers thick prepared with blade-coating and electrophoretic deposition
      methods, respectively, were embedded in the transistor devices for in situ
      conduction measurements as a function of battery cycles. During battery
      operation, the electronic and structural properties of Co3O4 NP films in the
      bulk, Co3O4/electrolyte, and Co3O4/current collector interfaces were spatially
      mapped to address the origin of the initial irreversible capacity loss from the
      first lithiation process. Further, change in carrier injection/extraction between
      the current collector and the Co3O4 NPs was explored using a modified
      electrochemical transistor device with multiple voltage probes along the
      electrical channel. 

PMID- 24895840
TI  - Measurement of a doubly substituted methane isotopologue, 13CH3D, by tunable
      infrared laser direct absorption spectroscopy.
AB  - Methane is an important energy resource and significant long-lived greenhouse
      gas. Carbon and hydrogen isotope ratios have been used to better constrain the
      sources of methane but interpretations based on these two parameters alone can
      often be inconclusive. The precise measurement of a doubly substituted methane
      isotopologue, (13)CH3D, is expected to add a critical new dimension to source
      signatures by providing the apparent temperature at which methane was formed or
      thermally equilibrated. We have developed a new method to precisely determine the
      relative abundance of (13)CH3D by using tunable infrared laser direct absorption
      spectroscopy (TILDAS). The TILDAS instrument houses two continuous wave quantum
      cascade lasers; one tuned at 8.6 MUm to measure (13)CH3D, (12)CH3D, and (12)CH4,
      and the other at 7.5 MUm to measure (13)CH4. With the use of an astigmatic
      Herriott cell with an effective path length of 76 m, a precision of 0.20/00
      (2sigma) was achieved for the measurement of (13)CH3D abundance in ca. 10 mL STP
      (i.e., 0.42 mmol) pure methane samples. Smaller quantity samples (ca. 0.5 mL STP)
      can be measured at lower precision. The accuracy of the Delta(13)CH3D measurement
      is 0.70/00 (2sigma), evaluated by thermally equilibrating methane with a range of
      deltaD values. The precision of +/-0.20/00 corresponds to uncertainties of +/-7 
      degrees C at 25  degrees C and +/-20  degrees C at 200  degrees C for estimates
      of apparent equilibrium temperatures. The TILDAS instrument offers a simple and
      precise method to determine (13)CH3D in natural methane samples to distinguish
      geological and biological sources of methane in the atmosphere, hydrosphere, and
      lithosphere. 

PMID- 24895839
TI  - RADOM, an efficient in vivo method for assembling designed DNA fragments up to 10
      kb long in Saccharomyces cerevisiae.
AB  - We describe rapid assembly of DNA overlapping multifragments (RADOM), an improved
      assembly method via homologous recombination in Saccharomyces cerevisiae, which
      combines assembly in yeasto with blue/white screening in Escherichia coli. We
      show that RADOM can successfully assemble ~3 and ~10 kb DNA fragments that are
      highly similar to the yeast genome rapidly and accurately. This method was tested
      in the Build-A-Genome course by undergraduate students, where 125 ~3 kb
      "minichunks" from the synthetic yeast genome project Sc2.0 were assembled. Here,
      122 out of 125 minichunks achieved insertions with correct sizes, and 102
      minichunks were sequenced verified. As this method reduces the time-consuming and
      labor-intensive efforts of yeast assembly by improving the screening efficiency
      for correct assemblies, it may find routine applications in the construction of
      DNA fragments, especially in hierarchical assembly projects.

PMID- 24895841
TI  - National trends and inpatient outcomes of inflammatory bowel disease patients
      with concomitant chronic liver disease.
AB  - BACKGROUND: There is little information on the frequency of chronic liver disease
      among hospitalized patients with inflammatory bowel disease (IBD). In this study,
      we seek to define the common etiologies contributing to chronic liver disease
      among IBD patients and to identify potential risk factors predictive of increased
      mortality in this population. METHODS: We analyzed the Nationwide Inpatient
      Sample from 1988 to 2006 to determine the frequency of chronic liver disease
      among patients with IBD and to determine their in-hospital outcomes. RESULTS:
      From 1988 to 2006, the age-adjusted rate of chronic liver disease among
      hospitalized patients with IBD has increased from 4.35 per 100,000 persons in
      1988-2001 to 7.45 per 100,000 persons in 2004-2006. The most common etiologies
      contributing to chronic liver disease among IBD patients were: primary sclerosing
      cholangitis, unspecified chronic hepatitis, chronic hepatitis C, and nonalcoholic
      fatty liver disease. Compared to IBD patients without liver disease, there was
      more than a twofold higher rate of inpatient morality among IBD patients with
      concomitant liver disease (2.7% vs. 1.3%, p < 0.01). The multivariate analysis
      showed that factors predictive of inpatient mortality include age >50,
      spontaneous bacterial peritonitis, ascites, hepatic encephalopathy, presence of
      cirrhosis, malnutrition, Clostridium difficile colitis, and hospital-acquired
      pneumonia. CONCLUSION: There is a higher rate of inpatient mortality among
      patients with concomitant IBD and chronic liver disease compared to IBD alone.
      Early recognition and management of complications related to portal hypertension
      among patients with IBD and chronic liver disease is particularly important in
      order to reduce inpatient mortality and morbidity.

PMID- 24895842
TI  - 3D flexible alignment using 2D maximum common substructure: dependence of
      prediction accuracy on target-reference chemical similarity.
AB  - A protein-bound conformation of a target molecule can be predicted by aligning
      the target molecule on the reference molecule obtained from the 3D structure of
      the compound-protein complex. This strategy is called "similarity-based docking".
      For this purpose, we develop the flexible alignment program fkcombu, which aligns
      the target molecule based on atomic correspondences with the reference molecule.
      The correspondences are obtained by the maximum common substructure (MCS) of 2D
      chemical structures, using our program kcombu. The prediction performance was
      evaluated using many target-reference pairs of superimposed ligand 3D structures
      on the same protein in the PDB, with different ranges of chemical similarity. The
      details of atomic correspondence largely affected the prediction success. We
      found that topologically constrained disconnected MCS (TD-MCS) with the simple
      element-based atomic classification provides the best prediction. The crashing
      potential energy with the receptor protein improved the performance. We also
      found that the RMSD between the predicted and correct target conformations
      significantly correlates with the chemical similarities between target-reference
      molecules. Generally speaking, if the reference and target compounds have more
      than 70% chemical similarity, then the average RMSD of 3D conformations is <2.0
      A. We compared the performance with a rigid-body molecular alignment program
      based on volume-overlap scores (ShaEP). Our MCS-based flexible alignment program
      performed better than the rigid-body alignment program, especially when the
      target and reference molecules were sufficiently similar. 

PMID- 24895843
TI  - Quantitative analysis and modelling of the behavioural dynamics of Salvelinus
      fontinalis (brook trout).
AB  - Behavioural sequences of juvenile brook trout Salvelinus fontinalis were
      investigated by time-lapse video-recording in the laboratory. A repertoire of six
      behavioural states was considered. Time-dependent probabilities of being in a
      given state, staying in the same state or changing of state, were derived from
      the behavioural profiles recorded continuously over time for each fish, during 2
      h on 2 days. A two-way factorial design with doubly repeated measures was applied
      to test the effects of stocking density (3 vs. 6 fish.150 l), ration level (1.2
      vs. 2.5%), feeding (before vs. after feeding) and time on these time-dependent
      probabilities. Feeding and time affected significantly the transition
      probabilities. A state space model was introduced using the estimated time
      dependent probabilities to capture the temporal structure of fish behaviour. The
      generated forecasts corresponded well to observed fish behaviour with R'(2)>=0.50
      for four behavioural states. 

PMID- 24895844
TI  - The effect of food deprivation on within-session patterns of wheel running.
AB  - In the present study, rats' wheel running was reinforced when they responded at
      different food deprivations. In experiment 1, fourths of a wheel turn were
      reinforced on a variable interval (VI) 15- or 60-s schedule during 50-min
      sessions. Subjects responded at 75, 85 or 95% of their free-feeding body weights,
      across conditions. Within-session decreases in responding were steepest at
      subjects' 75% weights for the VI 60-s schedule, but were similar at different
      weights for the VI 15-s schedule. In experiment 2, subjects responded on a VI 60
      s schedule at 75 or 95% of their free-feeding body weights. Reinforcer size was
      one or four food pellets. Steeper within-session decreases in responding were
      observed at subjects' 75% weight than at their 95% weight, with no effect of
      reinforcer amount. The present results cannot disconfirm either leading theory
      for within-session changes because the terms involved (i.e. habituation and
      satiation) are not adequately defined. However, the present results seem to pose
      problems for both explanations. 

PMID- 24895845
TI  - Operant conditioning of the visual smooth pursuit in young infants.
AB  - Smooth pursuit is a complex behaviour which is not considered as totally
      functional at birth. The lack of maturation of the visuo-motor systems is
      generally invoked to explain this phenomenon. However, if this oculomotor
      response is an operant behaviour, an alternate explanation may be found in the
      absence of previous confrontation with the environmental contingencies. A first
      group of young infants were placed in situations in which their oculomotor
      responses could produce an auditory stimulus. In such situations, young infants
      are able to improve their pursuit. Music was randomly delivered to a second
      group. No music was delivered to a third group. For the last two groups no
      augmentation of the proportion of slow movements was observed. Our main
      conclusion is that visual tracking has the properties of an operant behaviour and
      may be enhanced at birth. These results will be discussed within the frameworks
      of the behavioural discrepancy and of the maturationist hypotheses of the ocular
      motor control. 

PMID- 24895846
TI  - Detection of visual signals by rats: effects of signal intensity, event rate, and
      task type.
AB  - Animal models of human cognitive processes are being developed for investigating
      the neurobiological mechanisms of these processes and for identifying potential
      therapies for intoxication and neurodegenerative diseases. One promising method
      involves assessment of sustained attention in rats by use of a discrete-trial
      signal detection task. Several psychophysical and procedural factors have been
      identified in the literature that affect sustained attention in normal human
      subjects. Three key parameters that affect the level of performance, and whether
      that performance level deteriorates over time, include the quality of the signal,
      the event rate, and the type of task employed (simultaneous or successive
      discrimination). These three parameters were manipulated in this study to assess
      the degree of similarity in the behavior patterns engendered in rats by this
      signal detection task, in relation to the behavior observed in humans performing
      a variety of sustained attention tasks. Signal quality was manipulated by varying
      the increment in the intensity of a lamp (duration=300 ms), and event rate was
      varied among values of 4, 7, and 10 trials/min. The 'standard' detection task was
      used as a simultaneous discrimination and a successive discrimination task was
      designed in which a dim light flash was defined as a non-signal event and any of
      three brighter flashes were signal events. Accuracy of signal detection was
      quantified by the proportion of correct detections of the signal [P(hit)] and the
      proportion of false alarms [P(fa), i.e., incorrect responses on non-signal
      trials]. P(hit) fell with decreasing signal intensity, increasing event rate, and
      was lower in the discrimination task compared to the detection task. P(fa)
      increased with increasing event rate, but only in the detection task. A decrement
      in P(hit) across trial blocks was observed in the discrimination task primarily,
      and was most evident with a high event rate and dim signals. These data confirm
      that these tasks assess process(es) in rats that are very similar to those
      considered as sustained attention in humans. 

PMID- 24895847
TI  - Maintenance of male reaction to the congeneric song in the Hippolais warbler
      hybrid zone.
AB  - Both hybridization and competition may induce character shift on communication
      systems in hybrid zones, leading either to convergence or divergence. Melodious
      warblers Hippolais polyglotta and Icterine warblers H. icterina are
      interspecifically territorial and hybridize along a narrow contact zone. This
      spatial distribution is favoured by a reaction to the congeneric song. A
      character displacement, e.g. a decrease of the reaction, was expected within the
      hybrid zone because of reproduction costs lower than in allopatry. We
      investigated the pattern of variation of the interspecific reaction by comparing
      allopatric and sympatric populations. However, our data did not support the
      hypothesis character displacement and we propose several alternatives to account
      for the maintenance of interspecific reaction in sympatry. 

PMID- 24895848
TI  - Sex-related differences in spatial learning during the early postnatal
      development of the rat.
AB  - Some authors have reported that male rats younger than 21 days old are unable to
      perform spatial learning correctly because they have still not developed the
      ability to use extra-maze cues. In experiment 1, we analyzed spatial learning in
      14-, 21-, 30- and 42-day-old rats using the Morris water maze (MWM). According to
      our results, a good performance was observed in 30-day-old male rats whereas this
      was not observed in female rats until they were 42 days old. In experiment 2 we
      studied the role of sex hormones in this kind of learning using the MWM and 30
      day-old rats (castrated male rats and female rats treated with testosterone
      propionate (TP) after birth). The latter group, the male control group and the
      castrated males all solved the task correctly. The objective of experiment 3 was
      to determine possible differences between the sexes in the use of taxon
      strategies in the T water maze. To summarize, sexual dimorphism was only observed
      in spatial learning during development. 

PMID- 24895849
TI  - Conditional control of toxicosis-based conditioning by context.
AB  - This experiment with rat subjects used a conditional discrimination procedure to
      study the contextual control of flavour aversions. Rats were first given
      discrimination training with two distinctive contexts, such that a flavour was
      paired with lithium chloride (LiCl) in context A, alternating with presentations
      of the flavour alone in context B. Having learned this discrimination, the
      animals were now required to learn that a second flavour was followed by
      toxicosis in context B and nonreinforced in the other context. The rats were
      capable of learning to reject each of the flavours in the context where the fluid
      LiCl pairings had been given, but not in the alternative context. This result is
      interpreted as evidence that the context acts as an occasion setter in the sense
      that it controls the effectiveness of a conditioned aversion in a manner
      independent of any direct context-illness association. 

PMID- 24895850
TI  - Reconstructing folding energy landscapes by single-molecule force spectroscopy.
AB  - Folding may be described conceptually in terms of trajectories over a landscape
      of free energies corresponding to different molecular configurations. In
      practice, energy landscapes can be difficult to measure. Single-molecule force
      spectroscopy (SMFS), whereby structural changes are monitored in molecules
      subjected to controlled forces, has emerged as a powerful tool for probing energy
      landscapes. We summarize methods for reconstructing landscapes from force
      spectroscopy measurements under both equilibrium and nonequilibrium conditions.
      Other complementary, but technically less demanding, methods provide a model
      dependent characterization of key features of the landscape. Once reconstructed,
      energy landscapes can be used to study critical folding parameters, such as the
      characteristic transition times required for structural changes and the effective
      diffusion coefficient setting the timescale for motions over the landscape. We
      also discuss issues that complicate measurement and interpretation, including the
      possibility of multiple states or pathways and the effects of projecting multiple
      dimensions onto a single coordinate. 

PMID- 24895852
TI  - Live cell NMR.
AB  - Ever since scientists realized that cells are the basic building blocks of all
      life, they have been developing tools to look inside them to reveal the
      architectures and mechanisms that define their biological functions. Whereas
      "looking into cells" is typically said in reference to optical microscopy, high
      resolution in-cell and on-cell nuclear magnetic resonance (NMR) spectroscopy is a
      powerful method that offers exciting new possibilities for structural and
      functional studies in and on live cells. In contrast to conventional imaging
      techniques, in- and on-cell NMR methods do not provide spatial information on
      cellular biomolecules. Instead, they enable atomic-resolution insights into the
      native cell states of proteins, nucleic acids, glycans, and lipids. Here we
      review recent advances and developments in both fields and discuss emerging
      concepts that have been delineated with these methods. 

PMID- 24895851
TI  - Mechanisms of cellular proteostasis: insights from single-molecule approaches.
AB  - Cells employ a variety of strategies to maintain proteome homeostasis. Beginning
      during protein biogenesis, the translation machinery and a number of molecular
      chaperones promote correct de novo folding of nascent proteins even before
      synthesis is complete. Another set of molecular chaperones helps to maintain
      proteins in their functional, native state. Polypeptides that are no longer
      needed or pose a threat to the cell, such as misfolded proteins and aggregates,
      are removed in an efficient and timely fashion by ATP-dependent proteases. In
      this review, we describe how applications of single-molecule manipulation
      methods, in particular optical tweezers, are shedding new light on the molecular
      mechanisms of quality control during the life cycles of proteins. 

PMID- 24895854
TI  - Energetics of membrane protein folding.
AB  - Fundamental to the central goals of structural biology is knowledge of the
      energetics of molecular interactions. Because membrane proteins reside in a free
      energy minimum dictated by their sequences, their lipid environment, and water,
      one must understand the energetics of membrane protein folding to generate
      physical descriptions of cellular processes. Several technical obstacles have
      recently been overcome to enable folding measurements for membrane proteins in
      lipid and detergent micelle environments, and several new folding free energies
      have been published within the past ten years. This review discusses the
      challenges, successes, and novel insights into the physical basis underlying
      membrane protein folds. 

PMID- 24895853
TI  - Structural bioinformatics of the interactome.
AB  - The past decade has seen a dramatic expansion in the number and range of
      techniques available to obtain genome-wide information and to analyze this
      information so as to infer both the functions of individual molecules and how
      they interact to modulate the behavior of biological systems. Here, we review
      these techniques, focusing on the construction of physical protein-protein
      interaction networks, and highlighting approaches that incorporate protein
      structure, which is becoming an increasingly important component of systems-level
      computational techniques. We also discuss how network analyses are being applied
      to enhance our basic understanding of biological systems and their disregulation,
      as well as how these networks are being used in drug development. 

PMID- 24895855
TI  - Photocontrollable fluorescent proteins for superresolution imaging.
AB  - Superresolution fluorescence microscopy permits the study of biological processes
      at scales small enough to visualize fine subcellular structures that are
      unresolvable by traditional diffraction-limited light microscopy. Many
      superresolution techniques, including those applicable to live cell imaging,
      utilize genetically encoded photocontrollable fluorescent proteins. The
      fluorescence of these proteins can be controlled by light of specific
      wavelengths. In this review, we discuss the biochemical and photophysical
      properties of photocontrollable fluorescent proteins that are relevant to their
      use in superresolution microscopy. We then describe the recently developed
      photoactivatable, photoswitchable, and reversibly photoswitchable fluorescent
      proteins, and we detail their particular usefulness in single-molecule
      localization-based and nonlinear ensemble-based superresolution techniques.
      Finally, we discuss recent applications of photocontrollable proteins in
      superresolution imaging, as well as how these applications help to clarify
      properties of intracellular structures and processes that are relevant to cell
      and developmental biology, neuroscience, cancer biology and biomedicine. 

PMID- 24895858
TI  - Relationship between permeability glycoprotein (P-gp) gene expression and
      enrofloxacin metabolism in Nile Tilapia.
AB  - The aim of this study was to analyze the influence of permeability glycoprotein
      (P-gp) gene expression on enrofloxacin (ENR) metabolism in aquatic animals. Nile
      Tilapia Oreochomis niloticus were fed different doses of ENR ranging from 0 to 80
      mg/kg. The P-gp gene expression levels were determined by quantitative real-time
      PCR (qRT-PCR) at indicated time points after drug administration. Drug metabolism
      was determined by HPLC. The P-gp gene expression in liver and kidney was greatly
      enhanced 30 min after ENR administration at 40 mg/kg, peaked 3 h after drug
      administration, and then gradually decreased. Thirty minutes after a single oral
      administration of ENR (0, 20, 40, or 80 mg/kg), the P-gp gene expression
      increased in a dose-dependent manner. The P-gp gene expression levels in the
      kidney were significantly higher than those in the liver. Additionally, the
      metabolic rate of ENR in kidney was more rapid than that in liver. Furthermore, a
      close correlation was found between P-gp gene expression and ENR concentrations.
      These results suggest that P-gp may be involved in the ENR metabolism process in
      Nile Tilapia, providing a novel model for the potential utility of gene
      expression and drug metabolism studies in aquatic animals.

PMID- 24895859
TI  - Investigation of the link between broodstock infection, vertical transmission,
      and prevalence of Flavobacterium psychrophilum in eggs and progeny of Rainbow
      Trout and Coho Salmon.
AB  - The etiological agent of bacterial coldwater disease (BCWD), Flavobacterium
      psychrophilum, can be transmitted both vertically and horizontally. Outbreaks of
      BCWD can result in significant losses in salmonid aquaculture. Reduction of
      outbreaks in fry may be possible through implementation of a management strategy
      in which progeny of heavily infected broodstock are culled from the general
      population. Diagnostic assays to quantify F. psychrophilum concentrations in
      tissue samples and confirm presence of the bacterium in ovarian fluid have been
      previously validated. In the current study, these assays were used to screen 60
      female Rainbow Trout Oncorhynchus mykiss and 60 female Coho Salmon O. kisutch
      broodstock at two aquaculture facilities. Eyed eggs from 10 female broodstock
      (five fish from each facility) exhibiting graded levels of infection were
      transferred to the University of Idaho and monitored through early life stages
      for the presence of F. psychrophilum. Female Rainbow Trout broodstock were not
      positive for F. psychrophilum by enzyme-linked immunosorbent assay (ELISA) and
      prevalence was low in these progeny. However, ELISA optical density values for
      kidney correlated to F. psychrophilum prevalence in progeny (r = 0.938, P < 0.05)
      of Coho Salmon. Nested PCR on ovarian fluid was not a reliable indicator of
      vertical transmission in either species as broodstock ovarian fluid results did
      not correlate to F. psychrophilum prevalence in eyed eggs. Further research with
      these assays is necessary; however, results from this study indicate that
      broodstock screening may be a potential tool for evaluating F. psychrophilum
      infection levels, which could become an important component for disease
      management.

PMID- 24895860
TI  - Susceptibility of Koi and Yellow Perch to infectious hematopoietic necrosis virus
      by experimental exposure.
AB  - Infectious hematopoietic necrosis virus (IHNV) is a novirhabdoviral pathogen that
      originated in western North America among anadromous Pacific salmonids. Severe
      disease epidemics in the late 1970s resulting from IHNV's invasion into farmed
      Rainbow Trout Oncorhynchus mykiss in North America, Asia, and Europe emphasized
      IHNV's ability to adapt to new hosts under varying rearing conditions. Yellow
      Perch Perca flavescens and Koi Carp Cyprinus carpio (hereafter, "Koi") are
      aquaculture-reared fish that are highly valued in sport fisheries and the
      ornamental fish trade, respectively, but it is unknown whether these fish species
      are vulnerable to IHNV infection. In this study, we exposed Yellow Perch, Koi,
      and steelhead (anadromous Rainbow Trout) to IHNV by intraperitoneal injection
      (10(6) PFU/fish) and by immersion (5.7*10(5) PFU/mL) for 7 h, and monitored fish
      for 28 d. The extended immersion exposure and high virus concentrations used in
      the challenges were to determine if the tested fish had any level of
      susceptibility. After experimental exposure, Yellow Perch and Koi experienced low
      mortality (<6%) compared with steelhead (>35%). Virus was found in dead fish of
      all species tested and in surviving Yellow Perch by plaque assay and quantitative
      reverse transcription polymerase chain reaction (qPCR), with a higher prevalence
      in Yellow Perch than Koi. Infectious virus was also detected in Yellow Perch out
      to 5 d after bath challenge. These findings indicate that Yellow Perch and Koi
      are highly resistant to IHNV disease under the conditions tested, but Yellow
      Perch are susceptible to infection and may serve as possible virus carriers.

PMID- 24895862
TI  - Development of a nonlethal health assessment for wild Red Drum using a health
      index.
AB  - Nonlethal methods are needed to assess the health of wild fish and quantify the
      robustness of the broader population. Results could be used to indicate exposure
      to various stressors, such as contaminants, infectious disease, external parasite
      loads, and fishing pressure, to monitor changes in fish population health over
      time. The wild Red Drum Sciaenops ocellatus population in the Kennedy Space
      Center Reserve of Merritt Island National Wildlife Refuge was used to develop a
      protocol to define the health of free-ranging fish using nonlethal techniques.
      This health index incorporated morphometric measurements, weight, an evaluation
      for external parasite fauna, notation of physical deformities, and the presence
      of lesions. A total of 126 adult Red Drum were collected using hook-and-line
      angling during prespawning (May), spawning (September and October), and
      postspawning (December) periods. All fish were released alive back into their
      environment. The nonlethal health assessment scored fish in the "healthy" range
      of the health index during the prespawning and spawning periods. Fish caught
      during the postspawning period scored slightly below this range. Parasite load
      contributed to the depressed score during the postspawning period. Fish collected
      in all sampling periods were rated on average as "excellent" for condition
      factor, which suggests that the sampled population in the reserve were thriving.

PMID- 24895861
TI  - Risk factors associated with enteric septicemia of catfish on Mississippi
      commercial catfish farms.
AB  - A gram-negative bacterium, Edwardsiella ictaluri, is the cause of enteric
      septicemia of catfish (ESC), which is one of the most prevalent bacterial
      diseases in farm-raised catfish. The objective of this study was to identify risk
      factors associated with ESC mortalities and are reported by farm personnel. To
      identify risk factors a catfish management database was developed. The odds
      ratios (OR) of the final multivariable logistic regression model were: (1) volume
      of the pond (OR, 0.56), (2) interval from harvest until a mortality event (OR,
      1.49), (3) interval from stocking until a mortality event (OR, 0.52), (4) nitrite
      measured within 14 d of a mortality (OR, 3.49), (5) total ammonia measured within
      14 d of a mortality (OR, 20.48), and (6) sum of feed fed for 14 d prior to the
      disease outbreak (OR, 1.02), all of which were significantly (P <= 0.05)
      associated with ESC occurrence. This study showed that some commonly recorded
      production variables were associated with ESC outbreaks and if monitored could
      help identify "at risk" ponds prior to disease outbreaks.

PMID- 24895863
TI  - Comparative susceptibility of Channel Catfish, Blue Catfish, and their hybrid
      cross to experimental challenge with Bolbophorus damnificus (Digenea:
      Bolbophoridae) cercariae.
AB  - The digenetic trematode Bolbophorus damnificus has been implicated in significant
      losses in catfish aquaculture since the late 1990s. The complex life cycle
      sequentially involves the American white pelican Pelecanus erythrorhynchos, the
      marsh rams horn snail Planorbella trivolvis, and Channel Catfish Ictalurus
      punctatus. Research supports anecdotal reports from the industry, suggesting that
      the hybrid of Channel Catfish*Blue Catfish I. furcatus is less susceptible to
      disease agents that have been historically prohibitive to Channel Catfish
      production, namely the gram-negative bacteria Edwardsiella ictaluri and
      Flavobacterium columnare, as well as the myxozoan parasite Henneguya ictaluri.
      This current research compared the susceptibility of Channel Catfish, Blue
      Catfish, and their hybrid cross to an experimental challenge by B. damnificus.
      Fish were exposed to 0, 100, 200, and 400 B. damnificus cercariae per fish, and
      the numbers of metacercariae per fish were determined 14 d postchallenge.
      Metacercariae were recovered from all challenged fish. There were no significant
      differences among fish groups challenged with the same dose, suggesting Channel
      and Blue Catfish and their hybrid are comparably susceptible to B. damnificus
      infection. As such, it is recommended that producers raising hybrid catfish
      remain diligent in controlling populations of the snail intermediate host to
      prevent production losses attributed to B. damnificus, especially when loafing
      pelicans have been observed at the aquaculture operation.

PMID- 24895856
TI  - Fidelity of cotranslational protein targeting by the signal recognition particle.
AB  - Accurate folding, assembly, localization, and maturation of newly synthesized
      proteins are essential to all cells and require high fidelity in the protein
      biogenesis machineries that mediate these processes. Here, we review our current
      understanding of how high fidelity is achieved in one of these processes, the
      cotranslational targeting of nascent membrane and secretory proteins by the
      signal recognition particle (SRP). Recent biochemical, biophysical, and
      structural studies have elucidated how the correct substrates drive a series of
      elaborate conformational rearrangements in the SRP and SRP receptor GTPases;
      these rearrangements provide effective fidelity checkpoints to reject incorrect
      substrates and enhance the fidelity of this essential cellular pathway. The
      mechanisms used by SRP to ensure fidelity share important conceptual analogies
      with those used by cellular machineries involved in DNA replication,
      transcription, and translation, and these mechanisms likely represent general
      principles for other complex cellular pathways. 

PMID- 24895864
TI  - Association of mitochondrial dysfunction with oxidative stress and immune
      suppression in Blunt Snout Bream Megalobrama amblycephala fed a high-fat diet.
AB  - High-fat diets may have favorable effects on growth, partly based on protein
      sparing, but high-fat diets often lead to fatty liver (excessive fat deposition
      in the liver), which may be deleterious to fish growth and health. The goal of
      this study was therefore to investigate possible adverse effects and how they
      develop. Juvenile Blunt Snout Bream Megalobrama amblycephala (initial weight +/-
      SE = 17.70 +/- 0.10 g) were fed two diets (5% fat [control] or 15% fat). After 8
      weeks, fish that were fed the 15% fat diet showed a high rate of mortality and
      poor growth. The histological results clearly showed that the high fat intake
      resulted in fat and glycogen accumulation and structural alterations of the
      hepatocytes, mitochondria, and nuclei. In the high-fat group, impairments of the
      mitochondria included mitochondrial swelling and the loss of cristae and matrix.
      Fish that were given the 15% fat diet exhibited low succinate dehydrogenase and
      Na(+),K(+)-ATPase activities and increased cytochrome-c release from the
      mitochondria. Expression of genes for complex I and III subunits of the
      mitochondrial respiratory chain were down-regulated in fish that received the
      high-fat diet. Increases in malondialdehyde level and the ratio of oxidized
      glutathione to reduced glutathione suggested oxidative stress in the livers of
      fish from the high-fat diet group. Moreover, the lower leukocyte count, lysozyme
      and alternative complement activities, and globulin level in fish that received
      the high-fat diet indicated suppressive immune responses. Overall, the intake of
      excessive fat impaired mitochondrial bioenergetics and physiological functions.
      The dysfunction of the mitochondria subsequently mediated oxidative stress and
      hepatocyte apoptosis, which in turn led to the reduced efficacy of the immune
      system.

PMID- 24895857
TI  - Computational analysis of conserved RNA secondary structure in transcriptomes and
      genomes.
AB  - Transcriptomics experiments and computational predictions both enable systematic
      discovery of new functional RNAs. However, many putative noncoding transcripts
      arise instead from artifacts and biological noise, and current computational
      prediction methods have high false positive rates. I discuss prospects for
      improving computational methods for analyzing and identifying functional RNAs,
      with a focus on detecting signatures of conserved RNA secondary structure. An
      interesting new front is the application of chemical and enzymatic experiments
      that probe RNA structure on a transcriptome-wide scale. I review several proposed
      approaches for incorporating structure probing data into the computational
      prediction of RNA secondary structure. Using probabilistic inference formalisms,
      I show how all these approaches can be unified in a well-principled framework,
      which in turn allows RNA probing data to be easily integrated into a wide range
      of analyses that depend on RNA secondary structure inference. Such analyses
      include homology search and genome-wide detection of new structural RNAs. 

PMID- 24895865
TI  - The endemic copepod Calanus pacificus californicus as a potential vector of white
      spot syndrome virus.
AB  - The susceptibility of the endemic copepod Calanus pacificus californicus to white
      spot syndrome virus (WSSV) was established by the temporal analysis of WSSV VP28
      transcripts by quantitative real-time PCR (qRT-PCR). The copepods were collected
      from a shrimp pond located in Bahia de Kino Sonora, Mexico, and challenged per os
      with WSSV by a virus-phytoplankton adhesion route. Samples were collected at 0,
      24, 48 and 84 h postinoculation (hpi). The VP28 transcripts were not detected at
      early stages (0 and 24 hpi); however, some transcript accumulation was observed
      at 48 hpi and gradually increased until 84 hpi. Thus, these results clearly show
      that the copepod C. pacificus californicus is susceptible to WSSV infection and
      that it may be a potential vector for the dispersal of WSSV. However, further
      studies are still needed to correlate the epidemiological outbreaks of WSSV with
      the presence of copepods in shrimp ponds.

PMID- 24895866
TI  - Susceptibility of fish and turtles to three ranaviruses isolated from different
      ectothermic vertebrate classes.
AB  - Ranaviruses have been associated with mortality of lower vertebrates around the
      world. Frog virus 3 (FV3)-like ranaviruses have been isolated from different
      ectothermic vertebrate classes; however, few studies have demonstrated whether
      this pathogen can be transmitted among classes. Using FV3-like ranaviruses
      isolated from the American bullfrog Lithobates catesbeianus, eastern box turtle
      Terrapene carolina carolina, and Pallid Sturgeon Scaphirhynchus albus, we tested
      for the occurrence of interclass transmission (i.e., infection) and host
      susceptibility (i.e., percent mortality) for five juvenile fish and three
      juvenile turtle species exposed to each of these isolates. Exposure was
      administered via water bath (10(3) PFU/mL) for 3 d and survival was monitored for
      28 d. Florida softshell turtles Apalone ferox experienced no mortality, but 10%
      and 20% of individuals became infected by the turtle and fish isolate,
      respectively. Similarly, 5% of Mississippi map turtles Graptemys
      pseudogeographica kohni were subclinically infected with the turtle isolate at
      the end of the experiment. Channel Catfish Ictalurus punctatus experienced 5%
      mortality when exposed to the turtle isolate, while Western Mosquitofish Gambusia
      affinis experienced 10% mortality when exposed to the turtle and amphibian
      isolates and 5% mortality when exposed to the fish isolate. Our results
      demonstrated that interclass transmission of FV3-like ranaviruses is possible.
      Although substantial mortality did not occur in our experiments, the occurrence
      of low mortality and subclinical infections suggest that fish and aquatic turtles
      may function as reservoirs for FV3-like ranaviruses. Additionally, our study is
      the first to report transmission of FV3-like ranaviruses between fish and
      chelonians.

PMID- 24895867
TI  - Ontogeny of feeding and drinking in the greater rhea (Rhea americana).
AB  - Feeding and drinking movements of the greater rhea chick are analyzed. Feeding
      consists of five movements in the following sequence: orientation, pecking
      thrust, head lift, forward head jerk and swallow. Drinking is less complex,
      consisting of a downward movement followed by an upward movement. Adult movements
      are basically similar; there is a slight trend toward increased variability and
      decreased energy expenditure. Feeding movements are observed prior to feeding
      initiation. Drinking movements are first performed during initial water contact.
      Experience with food and water plays a major role in the development of response
      efficiency. 

PMID- 24895868
TI  - Imprinting in ducklings: variability among individuals and responses.
AB  - Duck embryos show a highly variable heart rate, which remains variable, though to
      a lesser degree, upon hatching. After hatching, behavioral responses of ducklings
      in an imprinting paradigm are also variable both between ducklings, and between
      particular responses (behavioral inter se and behavioral vs physiological).
      Nonetheless, responses, when viewed multi-dimensionally, do appear to cluster,
      suggesting that there exist a variety of discrete developmental 'types', even
      among an inbred strain of ducklings. 

PMID- 24895869
TI  - Behavioural responses to visual stimuli following posterior dorsal telencephalic
      ablations in Gallus domesticus.
AB  - The behaviour of chickens following posterior dorsal telencephalic ablations was
      studied in response to humans, strange hens, aerial predators, ground predators
      and a visual startle stimulus. The ablations had no effect on the birds' response
      to either the aerial or ground predator but there was a significant reduction in
      pacing after the visual startle stimulus. Following posterior telencephalic
      ablation the birds showed significantly fewer attacks and threats in encounters
      with unfamiliar hens but showed exaggerated escape/avoidance behaviour to humans
      in both their home pens and in experimental testing cages. The reasons for this
      avoidance behaviour to humans are discussed but no definite conclusions could be
      drawn. 

PMID- 24895870
TI  - Effects of early electrical stimulation of the lateral hypothalamus on the
      delayed acquisition of approach and avoidance learning tasks in the rat.
AB  - Three experiments indicated the effects of an early bilateral stimulation of the
      lateral hypothalamus on later learning behaviour of male rats. The animals were
      stimulated at 15 days of age and tested during the sixth week of life. Stimulated
      rats showed an improvement of performances in acquisition of a food-reinforced
      operant conditioning, but their performance was impaired in two avoidance tests,
      an inhibitory avoidance response and a two-way avoidance test. These results
      cannot be interpreted in terms of handling or early experience. An hypothesis of
      a modified synaptic competition favouring circuits which assure the regulation of
      approach behaviours is formulated. 

PMID- 24895871
TI  - Behavioural conflict in two strains of rat: Home cage preference versus dark
      preference.
AB  - When confronted with a novel situation rats show a tendency either to stay in a
      dark place or to retreat to a familiar place, if available. To produce a conflict
      between these two tendencies the rat's home cage was connected by a runway to a
      dark but unfamiliar compartment. Three groups of rats were tested in this
      apparatus with different levels of illumination in the home cage. Tryon Maze
      Bright rats showed a strong preference for the home cage which was independent of
      the illumination level. This preference was also found in Wistar rats. With a
      very high level of illumination in the home cage, however, Wistar rats showed a
      preference for the home cage only in the first few trials or a series of repeated
      trials. In later trials they spent more time in the dark part of the apparatus.
      The results were regarded as an indication that in a novel situation rats
      primarily search for a familiar place. When such a place is available they
      tolerate aversive stimulation present in this place. 

PMID- 24895872
TI  - Social roles in captive vervet monkeys (Cercopithecus aethiops sabaeus).
AB  - Behavior clusters were identified through factor analysis of individual behavior
      profiles over time and across groups of different composition in a captive vervet
      monkey (Cercopithecus aethiops sabaeus) colony. The six resulting factors were
      assessed through examination of (1) the behaviors contributing to each factor,
      (2) the properties of the factors across groups, and (3) the distribution of
      individuals along the factor dimensions. Three of the clusters were judged to
      represent the social roles of Control Male, Control Female, and Subordinate and
      the other three described the behaviors associated with the developmental stages
      of yearling (Playful-Protected), juvenile female (Infant focus) and juvenile male
      (Sex-Play). 

PMID- 24895877
TI  - Thyroid cancer: radiation safety precautions in 131I therapy based on actual
      biokinetic measurements.
AB  - PURPOSE: To formulate radiation precautions for patients with thyroid cancer who
      are undergoing thyroid hormone withdrawal-induced hypothyroidism and iodine 131
      ((131)I) therapy through actual biokinetic measurements. MATERIALS AND METHODS:
      Informed consent and institutional review board approval were obtained. From
      October 2008 to December 2011, consecutive patients with differentiated thyroid
      cancer who had been prepared for (131)I ablation treatment or (131)I treatment
      for metastatic disease during follow-up were prospectively recruited.
      Calculations based on deduced whole-body retention and measured iodine
      biokinetics in thyroidal tissue were derived to determine the thyroidal and
      extrathyroidal compartment uptake fractions and effective half-lives. Precaution
      times necessary to avoid close contact with family members and the general public
      were derived from these parameters and regulatory dose limits. RESULTS: Seventy
      seven patients (36 with ablation treatments, 41 with follow-up treatments) were
      eligible for the analysis. Actual dose rates from patients after therapeutic
      (131)I administration were greatly lower than those described in the American
      Thyroid Association (ATA) and Nuclear Regulatory Commission (NRC) models: The
      mean initial dose rate at 0.3 m for patients with ablation treatment was only 28%
      (0.183/0.655 uSv/h/MBq) +/- 2.9 (standard deviation) (range, 12.1%-38.3%) and 36%
      (0.183/0.511 uSv/h/MBq) +/- 3.7 (range, 15.5%-49.1%) of that described in the NRC
      and ATA models, respectively; the equivalent values for patients with follow-up
      treatment were only 30% (0.195/0.655 uSv/h/MBq) +/- 3.5 (range, 12.5%-45.3%) and
      38% (0.195/0.511 uSv/h/MBq) +/- 4.5 (range, 16.0%-58.1%), respectively. The
      actual mean effective (131)I half-life in the thyroid remnant tissue was greatly
      lower than that described in the ATA and NRC models: 47.6 versus 175.2 hours.
      CONCLUSION: On the basis of the current dose limits, typically administered
      activities of 3.7 GBq to a patient with ablation treatment or 7.4 GBq to a
      patient with follow-up treatment required 3 days of sleeping apart for keeping
      the doses to pregnant women and children below 1 mSv. No precautions were
      required for non-cosleeping nonpregnant adult family members.

PMID- 24895879
TI  - Plato and the easter bunny.

PMID- 24895880
TI  - Rats' memory for event duration: differential effects of delaying the
      discriminative choice cue as opposed to the opportunity to execute the choice
      response.
AB  - Rats were trained to discriminate short or long durations of houselight
      illumination using a choice procedure. During the test phase of each trial, the
      left and right levers were presented with an auditory cue above one of them on
      (cued lever) while the other was off (uncued lever). The auditory cue was
      presented immediately after sample offset and the levers were inserted after the
      auditory cue had been presented for 2 s. For half of the rats, the correct
      response following the short sample was to press the cued lever, while following
      the long sample, it was to press the uncued lever. This was reversed for the
      remaining rats. Following acquisition of the discrimination, two different types
      of delay tests were administered. In the first set, the delay between offset of
      the sample and onset of the auditory cue was manipulated (Cue Delay Test). In the
      second set, the delay between onset of the auditory cue and entry of the levers
      into the chamber was manipulated (Response Delay Test). Cue Delay testing
      resulted in a choose-long bias at the longer delays. Response Delay testing did
      not result in a systematic response bias and there was little forgetting over the
      delay interval. These data suggest that the rats did not stop the internal clock
      when the nominal sample was offset, but allowed it to keep running until the
      auditory cue was presented. The data from the Response Delay Test indicate that
      either a response decision was made based on the clock reading as soon as the
      auditory cue was presented, or the clock reading itself was retained over the
      delay with no subjective shortening and little forgetting. 

PMID- 24895881
TI  - Scrounger numbers and the inhibition of social learning in pigeons.
AB  - Social foraging can inhibit the learning and performance of food-finding
      behaviours. Confusion, overshadowing and frequency-dependent payoffs may all
      contribute to the inhibition, but standard experimental procedures make the
      separation of these effects difficult. In this study, we combine characteristics
      of cage and aviary experiments and present either a single naive pigeon or groups
      of three naive pigeons with a pre-trained producer opening an apparatus in an
      aviary. All naive birds scrounged on the 3456 openings they witnessed. In a post
      test given in the absence of other birds, all single scroungers opened the
      apparatus, but only one of the group-scrounging pigeons did. Scrounger numbers
      appear to play an important role in the inhibition of food-finding behaviour,
      suggesting that confusion is a major component of learning in a social context. 

PMID- 24895882
TI  - Experimental tests to assess emotionality in horses.
AB  - Different tests were used to assess different aspects of the emotionality of 1-3
      year-old horses: arena test; a 'novel object' test; and a handling test. In
      reaction to the test situations no important differences were observed according
      to age or sex in the behaviour patterns, but clear individual differences were
      observed within these classes. The arena test seemed to reveal the degree of
      gregariousness of the animals whereas the results in the two other tests were
      correlated and seemed to reflect an inherent degree of fearfulness in the horse.
      Indices were developed that enabled to rank the animals, by taking into account
      all behaviour patterns shown. Such individual characteristics might have some
      genetic basis: half-siblings tended to behave the same way in most cases. 

PMID- 24895883
TI  - Dynamics of temporal control in rats: the effects of a brief transition in
      interval duration.
AB  - Five rats lever-pressed for liquid reinforcers delivered according to a fixed
      interval (FI) reinforcement schedule, where the interval requirement changed at
      an unpredictable point within a session. In a short square wave (SSW) condition,
      eight 30-s intervals were intercalated in a series of 120-s intervals so that the
      intervals changed from 120 to 30 s then back to 120 s. In a long square wave
      (LSW) condition the intervals changed from 120 to 480 s then back to 120 s. We
      observed rapid temporal control of post-reinforcement wait time duration by the
      IFI duration in the SSW condition only: Wait times decreased significantly during
      a transition to shorter (30 s) intervals; whereas wait times did not reliably
      increase during a transition to longer (480 s) intervals. Furthermore, in the SSW
      condition, wait time in post-transition intervals was shorter than that observed
      during pre-transition intervals. The results show that rats' wait times are
      sensitive to moment-to-moment changes in interval duration and that the dynamics
      depend on the direction in which the intervals change. 

PMID- 24895884
TI  - Concurrent schedule performance in domestic goats: persistent undermatching.
AB  - Performance of nine domestic goats responding under concurrent variable-interval
      variable-interval schedules of food delivery was examined, with results analyzed
      in terms of the generalized matching equation. Substantial undermatching of
      response and time allocation ratios to obtained reinforcement ratios was evident.
      Post-reinforcement pause time ratios approximately matched obtained reinforcement
      ratios. Subtracting these times from total time allocation values yielded net
      time allocation ratios, which undermatched obtained reinforcement ratios to a
      greater degree than whole-session time allocation ratios. Slopes of regression
      lines relating behavioral outputs to environmental inputs characteristically were
      below 0.6, which is similar to previous findings in dairy cows tested under
      comparable conditions. 

PMID- 24895885
TI  - Wood dispersion affects home range size of female roe deer.

PMID- 24895886
TI  - Group leaving in Mountain goats: are young males ousted by adult females?

PMID- 24895887
TI  - Study on the antioxidant and antimicrobial activities of Allium ursinum L.
      pressurised-liquid extract.
AB  - Allium ursinum L. is widely used as a spice as well as a traditional medicine.
      The aim of this work was to evaluate the antioxidant and antimicrobial activities
      (AMAs) of A. ursinum extract, obtained by pressurised-liquid extraction. Several
      reliable procedures such as 2,2-diphenyl-1-picrylhydrazyl, 2,2-azinobis-3ethyl
      benxothiazoline-6-sulphonic acid, ferric-reducing antioxidant power assay and
      oxygen radical absorbance capacity assays were carried out. Vegetable oil
      stability was evaluated by using Rancimat test. Moreover, AMA was performed on
      different microorganisms. On the basis of the results obtained, it is confirmed
      that the A. ursinum extract could be used as a natural ingredient in food and/or
      pharmaceutical industries. 

PMID- 24895878
TI  - Recanalization and clinical outcome of occlusion sites at baseline CT angiography
      in the Interventional Management of Stroke III trial.
AB  - PURPOSE: To use baseline computed tomographic (CT) angiography to analyze imaging
      and clinical end points in an Interventional Management of Stroke III cohort to
      identify patients who would benefit from endovascular stroke therapy. MATERIALS
      AND METHODS: The primary clinical end point was 90-day dichotomized modified
      Rankin Scale (mRS) score. Secondary end points were 90-day mRS score distribution
      and 24-hour recanalization. Prespecified subgroup was baseline proximal
      occlusions (internal carotid, M1, or basilar arteries). Exploratory analyses were
      subsets with any occlusion and specific sites of occlusion (two-sided alpha =
      .01). RESULTS: Of 656 subjects, 306 (47%) underwent baseline CT angiography or
      magnetic resonance angiography. Of 306, 282 (92%) had arterial occlusions. At
      baseline CT angiography, proximal occlusions (n = 220) demonstrated no difference
      in primary outcome (41.3% [62 of 150] endovascular vs 38% [27 of 70] intravenous
      [IV] tissue-plasminogen activator [tPA]; relative risk, 1.07 [99% confidence
      interval: 0.67, 1.70]; P = .70); however, 24-hour recanalization rate was higher
      for endovascular treatment (n = 167; 84.3% [97 of 115] endovascular vs 56% [29 of
      52] IV tPA; P < .001). Exploratory subgroup analysis for any occlusion at
      baseline CT angiography did not demonstrate significant differences between
      endovascular and IV tPA arms for primary outcome (44.7% [85 of 190] vs 38% [35 of
      92], P = .29), although ordinal shift analysis of full mRS distribution
      demonstrated a trend toward more favorable outcome (P = .011). Carotid T- or L
      type occlusion (terminal internal carotid artery [ICA] with M1 middle cerebral
      artery and/or A1 anterior cerebral artery involvement) or tandem (extracranial or
      intracranial) ICA and M1 occlusion subgroup also showed a trend favoring
      endovascular treatment over IV tPA alone for primary outcome (26% [12 of 46] vs
      4% [one of 23], P = .047). CONCLUSION: Significant differences were identified
      between treatment arms for 24-hour recanalization in proximal occlusions; carotid
      T- or L-type and tandem ICA and M1 occlusions showed greater recanalization and a
      trend toward better outcome with endovascular treatment. Vascular imaging should
      be mandated in future endovascular trials to identify such occlusions. Online
      supplemental material is available for this article.

PMID- 24895890
TI  - Electrically controlled drug-delivery system may help minimize side effects.

PMID- 24895888
TI  - Inflammatory response of monocytes to ambient particles varies by highway
      proximity.
AB  - Epidemiological studies have demonstrated associations of chronic respiratory
      disease with near-roadway pollutant exposure, effects that were independent of
      those of regional air pollutants. However, there has been limited study of the
      potential mechanisms for near-roadway effects. Therefore, we examined the in
      vitro effect of respirable particulate matter (PM) collected adjacent to a major
      Los Angeles freeway and at an urban background location. PM was collected on
      filters during two consecutive 15-day periods. Oxidative stress and inflammatory
      response (intracellular reactive oxygen species [ROS], IL-1beta, IL-6, IL-8, and
      TNF-alpha) to PM aqueous extract was assessed in THP-1 cells, a model for
      evaluating monocyte/macrophage lineage cell responses. The near-roadway PM
      induced statistically significantly higher levels of IL-6, IL-8, and TNF-alpha (P
      < 0.01) and a near significant increase in IL-1beta (P = 0.06) but did not induce
      ROS activity (P = 0.17). The contrast between urban background and near-roadway
      PM-induced inflammatory cytokines was similar in magnitude to that corresponding
      to temporal differences between the two collection periods. PM-induced
      proinflammatory protein expression was attenuated by antioxidant pretreatment,
      and PM stimulation enhanced the activity of protein kinases, including
      extracellular signal-regulated kinase and c-Jun N-terminal kinase. Pretreatment
      of THP-1 cells with kinase inhibitors reduced PM-induced proinflammatory mediator
      expression. The proinflammatory response was also reduced by pretreatment with
      polymyxin B, suggesting a role for endotoxin. However, the patterns of PM-induced
      protein kinase response and the attenuation of inflammatory responses by
      antioxidant or polymyxin B pretreatment did not vary between near-roadway and
      urban background locations. We conclude that near-roadway PM produced greater
      inflammatory response than urban background PM, a finding consistent with
      emerging epidemiologic findings, but these differences were not explained by PM
      endotoxin content or by MAPK pathways. Nevertheless, THP-1 cells may be a model
      for the development of biologically relevant metrics of long-term spatial
      variation in exposure for study of chronic disease. 

PMID- 24895889
TI  - Mechanistic insights into the substrate recognition of PPO: toward the rational
      design of effective inhibitors.

PMID- 24895891
TI  - Insights into the bonding pattern for characterizing the open and closed state of
      the substrate-binding loop in Mycobacterium tuberculosis InhA.
AB  - BACKGROUND: Direct InhA inhibitors, which interact with the substrate-binding
      loop (SBL) and order it into a closed state, are thought to be potential anti
      multidrug-resistant tuberculosis molecules. Thus, developing parameters to
      distinguish between the open and closed state of SBL can help in screening the
      potent inhibitors with loop ordering properties. RESULTS: We report empirical
      parameters to differentiate the 'open' and 'closed' conformation of SBL by
      comprehensive ana-lysis of InhA crystal structures. The 'open' state of SBL was
      observed with intra- and inter-loop H-bonding within the residues pair, G205-G208
      and L207-I105, respectively, while the 'closed' conformation is found with H
      bonding within the residues pair: L207-E210 and A206-I105. Moreover, potent
      inhibitors (IC50, 5.3-5160 nM) are observed to make hydrophobic interactions with
      residues of SBL, particularly with A198 in the structures with closed state of
      SBL. CONCLUSION: The observed set of H-bonding pattern and hydrophobic contact
      with residues of SBL can be utilized as a filter to evaluate novel inhibitors for
      their SBL ordering properties and potencies using the molecular dynamic
      simulation in the virtual screening of direct InhA inhibitors.

PMID- 24895892
TI  - Halogen-enriched fragment libraries as chemical probes for harnessing halogen
      bonding in fragment-based lead discovery.
AB  - Halogen bonding has recently experienced a renaissance, gaining increased
      recognition as a useful molecular interaction in the life sciences. Halogen bonds
      are favorable, fairly directional interactions between an electropositive region
      on the halogen (the sigma-hole) and a number of different nucleophilic
      interaction partners. Some aspects of halogen bonding are not yet understood well
      enough to take full advantage of its potential in drug discovery. We describe and
      present the concept of halogen-enriched fragment libraries. These libraries
      consist of unique chemical probes, facilitating the identification of favorable
      halogen bonds by sharing the advantages of classical fragment-based screening.
      Besides providing insights into the nature and applicability of halogen bonding,
      halogen-enriched fragment libraries provide smart starting points for hit-to-lead
      evolution. 

PMID- 24895893
TI  - Antimicrobial clay-based materials for wound care.
AB  - The historical use of clay minerals for the treatment of wounds and other skin
      ailments is well documented and continues within numerous human cultures the
      world over. However, a more scientific inquiry into the chemistry and properties
      of clay minerals emerged in the 19th century with work investigating their role
      within health gathering pace since the second half of the 20th century. This
      review gives an overview of clay minerals and how their properties can be
      manipulated to facilitate the treatment of infected wounds. Evidence of the
      antimicrobial and healing effects of some natural clay minerals is presented
      alongside a range of chemical modifications including metal-ion exchange, the
      formation of clay-drug composites and the development of various polymer-clay
      systems. While the evidence for applying these materials to infected wounds is
      limited, we contextualize and discuss the future of this research. 

PMID- 24895894
TI  - The design of novel classes of macrolides for neutrophil-dominated inflammatory
      diseases.
AB  - Neutrophil-dominated inflammatory diseases, like chronic obstructive pulmonary
      disease, cystic fibrosis, bronchiectasis, bronchiolitis obliteras syndrome and
      non-eosinophilic asthma, present a significant medical problem lacking adequate
      therapy. Macrolide antibiotics have been reported to be effective in the
      treatment of the aforementioned diseases, for reasons unrelated to their
      antibacterial action. This has resulted in research activities aimed at gaining a
      better understanding of the immunomodulatory actions of macrolides and the
      synthesis of various novel anti-inflammatory macrolides without antimicrobial
      activity. Despite the difficult chemistry and lack of an extensive knowledge for
      their mechanism of action, several interesting molecules from this class,
      including potential clinical candidates, are on the horizon. 

PMID- 24895895
TI  - Bruton's TK inhibitors: structural insights and evolution of clinical candidates.
AB  - Bruton's TK (BTK) is a promising biological target for therapeutic intervention
      of several diseases including inflammatory diseases and cancer/B cell
      malignancies. Numerous research groups are actively engaged in investigating the
      functions of BTK, and discovering potent and selective BTK inhibitors as drug
      candidates. Revealed by x-ray crystal structures with ligands of diverse chemical
      structures, the ability of BTK kinase domain to adopt various inactive
      conformations offers unique opportunities to identify highly potent and
      exquisitely selective inhibitors. Both reversible and covalent inhibitor
      approaches have yielded candidates demonstrating safety profiles and efficacies
      in multiple preclinical models of autoimmunity and oncology. Two BTK inhibitors
      have entered human clinical trials for oncology indications. Ibrutinib won the US
      FDA approval in November 2013 to become the first-in-class BTK inhibitor for
      treating mantle cell lymphoma. This encouraging outcome and the other on-going
      human studies could ultimately expand the utility of BTK inhibitors to broader
      autoimmune disease areas. 

PMID- 24895896
TI  - Monoamine oxidase A and B substrates: probing the pathway for drug development.

PMID- 24895897
TI  - The Great Wall Symposium.

PMID- 24895899
TI  - Facial displays and political leadership in France.
AB  - Although nonverbal cues of dominance and the emotional responses they elicit have
      been well known since antiquity, the facial displays associated with successful
      political leadership have a direct political impact on the electorate in the
      television age. The effects of these stimuli can be studied experimentally from
      the perspective of human ethology. Recent findings indicate that expressive
      displays like those of nonhuman primates have similar effects when exhibited by
      human leaders in France and the United States but that cultural differences in
      expected behavior may significantly modify their effects. 

PMID- 24895898
TI  - Wasabi-derived 6-(methylsulfinyl)hexyl isothiocyanate induces apoptosis in human
      breast cancer by possible involvement of the NF-kappaB pathways.
AB  - 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a bioactive ingredient of
      wasabi (Wasabia japonica), which is a popular spice in Japan. 6-MSITC has been
      reported to inhibit the proliferation of breast cancer and melanoma cell lines.
      We inoculated 30 female Balb-nu/nu mice with MDA-MB-231 or -453 cells, and orally
      administered varying concentrations of 6-MSITC for 12 days following tumor
      growth. The tumor volumes and tumor weights from mice inoculated with MDA-MB-231
      cells, and the tumor volumes of MDA-MB-453 cells were significantly inhibited by
      6-MSITC on Days 9 and 11 after drug administration. DNA fragmentation, DNA
      ladder, and caspase 3/7 activity performed in vitro revealed that 6-MSITC induced
      apoptosis of MDA-MB-231, MDA-MB-453, and MCF-7 cells. Furthermore, nuclear factor
      kappaB (NF-kappaB) expression in the nuclei and phosphorylation of inhibitor
      kappaBalpha (IkappaBalpha) was downregulated by 6-MSITC in a concentration
      dependent manner; however, this activity was not observed in MCF-7 cells.
      Moreover, this downregulation of phosphorylated IkappaBalpha by 6-MSITC in MDA-MB
      231 and -453 cells supports its inhibitory effects on NF-kappaB activity. The
      expression of phosphorylated AKT (pAKT) reduced by 6-MSITC was confirmed in MDA
      MB-231 cells. Thus, we conclude that 6-MITC promotes apoptosis of breast cancer
      cells by inhibiting NF-kB and therefore releasing its control of the PI3K/AKT
      pathway.

PMID- 24895900
TI  - Reproductive behavior and physiology of nulliparous female rats after sexual
      experience.
AB  - There is an extensive literature suggesting that following sexual experience male
      mammals show chronic elevation of sexual behavior and growth of reproductive
      organs and glands. An hypothesis was examined in the present research that a
      similar pattern of changes would be revealed in females after sexual contact
      without the confounding influences of pregnancy and parturition. Initiatially
      virgin gonadally intact (Experiment I) and ovariectomized/hormone-injected
      (Experiment 1) female rats received precisely controlled interactions either with
      intact males to gain copulatory experience or with castrated males to gain social
      experience without copulating. Subsequently, females from each condition were
      observed during behavioral estrus with unfamiliar males, and all females were
      sacrificed the following day. Behavioral results were similar for the two
      experiments and failed to support the hypothesis. It was the virgin, rather than
      the experienced female, which solicited a male more frequently and aggressively
      rejected his approaches less often. Moreover, the male exhibited more and faster
      intromissions and ejaculations with inexperienced than with experienced females.
      Physiological analyses of ovaries, uteri, utero-tubal junctions, vaginae,
      clitorides and preputials suggested subtle quantitative and qualitative changes
      after sexual contact, but only in intact females and without any clear pattern of
      changes. Conclusions were that the striking modifications in behavior are
      centrally mediated in the female and are unlike those observed in the sexually
      experienced male. Nevertheless, the consequence for fecundity may be the same for
      both genders. 

PMID- 24895902
TI  - Social tendencies of the Corsican Mouflon Ovis ammon musimon in the caroux
      espinouse massif (South of France).
AB  - Mouflons, according to their age and sex, show particular social tendencies
      during the annual cycle. During its life, each individual builds on its own
      "ontogenetic social trajectory" whose annual variations are representative of its
      social tendencies. Males and females present major differences from the beginning
      of their second year of life. As they grow older, a process of social segregation
      develops between the sexes. Individual behaviour is considered here as one of the
      major causes of group formation in mouflons. This point of view, inspired by
      Mason, appears quite complementary to Hinde's conceptual framework and leads us
      to a new viewpoint of social system in ungulates. 

PMID- 24895901
TI  - Fidelity to the breeding site in the alpine newt Triturus Alpestris.
AB  - In a context of several closed breeding sites (archipelago model), the great
      majority of alpine newts are sedentary, visiting the same site during two
      successive years. A homing experiment offered the animals a choice between two
      breeding sites, one from which they came and the other which was inhabited by
      another population. This experiment demonstrates the fidelity of a great majority
      of newts for their site of origin. Fidelity was stronger when sites were distant
      (150 m) than when nearer (25 m). The speed and the probability of return still
      varied according to both the distance and the nature of the environment of the
      release point. The performances were better when the animals were released in the
      wood than when released in the pasture. The mechanisms of orientation and
      navigation which should explain such results, as well as the genetic consequences
      of the fidelity, are examined and discussed. 

PMID- 24895903
TI  - Feralization: The making of wild domestic animals.
AB  - The widely accepted viewpoint that feralization is the reverse of domestication
      requires that the feralization process be restricted to populations of animals
      and, therefore, cannot occur in individuals. An alternative, ontogenetic approach
      is presented in which feralization is defined as the process by which individual
      domestic animals either become desocialized from humans, or never become
      socialized, and thus behave as untamed, non-domestic animals. Feralization will
      vary among species and, intraspecifically, will depend upon an individual's age
      and history of socialization to humans. Because feralization is not equated with
      morphological change resulting from evolutionary processes, species formation is
      not an accurate indicator of feral condition. 

PMID- 24895904
TI  - Foraging by rats: Intuitions, models, data.
AB  - Rats R. norvegicus were trained to press levers to accumulate food at distant
      sites. The size of the hoard increased with the distance to the site, but did not
      vary when the rats had to run uphill or downhill to get it. Persistence in a
      patch depended on the richness of the alternative patch. Optimality models were
      developed and modified in light of these data. 

PMID- 24895905
TI  - Male competition facing one conspecific female in the cave-living bathysciinae
      speonomus delarouzeei fairm. (Coleoptera, Catopidae).
AB  - When 2 S. delarouzeei males face one female, the latter does not choose between
      them, she copulates with the male which wants to mate. There is considerable
      aggression when the both want to copulate. The aggression rate is the highest in
      triplets in which both males copulate. In most cases, the males mate
      consecutively in spite of competitor attacks. This behavior protects the female
      against a sterile male. It may take place in caves where large numbers of
      individuals are observed around food sources. 

PMID- 24895907
TI  - Development of dominance in domestic rats in laboratory and seminatural
      environments.
AB  - Dominance hierarchies were studied in mixed-sex colonies of albino rats Rattus
      norvegicus reared and housed in three different types of physical environments.
      Colonies were observed. In either an outdoor pen, an indoor pen, or in laboratory
      cases for a period of 24 weeks initiated at 35 days of age. In both pen colonies,
      male dominance relationships were based on the asymmetric display of biting
      attacks by dominants and the unequivocal display of submissive postures by
      subordinates. These behaviours did not fully develop, nor did dominance emerge
      until males were 140-150 days of age. No asymmetric display of attacks and
      submission, nor dominance relationships were observed in two different types of
      laboratory cage settings; these males continued to play fight throughout
      adulthood. However, males of all colony types attacked male intruders. The nature
      of the physical environment appeared to have a powerful influence on the
      development of dominance, but did not affect agonistic behaviour directed toward
      intruders. 

PMID- 24895906
TI  - Grasshopper mouse's use of visual cues during a predatory attack.
AB  - This study examined the grasshopper mouse's use of visual cues to recognize a
      potential prey. The mouse's latency of attack was measured in response to models
      presented in five experiments. The mice responded to the contrast, movement and
      relative size of a visual stimulus, but did not respond to different orientations
      or shapes. Furthermore, the mice did not learn to recognize a particular prey by
      its shape or by a combination of visual cues. Essentially, the mice used vision
      primarily to detect and follow a potential prey rather than to recognize a
      particular species. The significance of the mouse's use of visual cues compared
      with olfactory and auditory cues was discussed. 

PMID- 24895908
TI  - Effect of conditional discrimination learning on subsequent multiple-cue
      discrimination in children.
AB  - Thirty-six five-year old children were exposed to a visual multiple-cue
      discrimination task and to a test which assessed the control over responding
      acquired by the cues. The training and the test followed a treatment that varied
      between three groups of twelve children. A conditional discrimination task and a
      multiple-cue discrimination task were arranged in two different groups. No
      pretraining was given to a third group. Conditional discrimination training led
      to fewer errors on the test that followed the multiple-cue task than each of the
      other treatments. There was no reliable different between the numbers of errors
      after the other treatments. The results can be explained by an observing response
      account of transfer in discrimination learning. 

PMID- 24895909
TI  - Maternal influences on food preferences in weanling mice Mus domesticus.
AB  - This study has been designed to evaluate the role of social (maternal) influences
      on the development of feeding behaviour in mice. A large enclosure, allowing
      direct observation, was divided into three separate areas: a central area for the
      nest and two side feeding areas at opposite ends. In one the young could feed
      with their mother, in the other one the young had to feed on their own. Three
      different groups were studied: one had the same food in the two feeding areas:
      the second had a less palatable food in the mother feeding area: the third had
      two different kinds of food with similar palatability in the feeding areas. The
      development of infants' behaviour expressed as: a) order of exit from the nest;
      b) first direction taken on leaving the nest; c) first food consumed: d)
      frequency of contacts with mother or pup food was electronically recorded and
      analysed. The results clearly show that weanling mice strongly prefer to follow
      their mother at her feeding sites even when the mother's food is less palatable
      than their own. Furthermore infants of one group, in a following binary choice
      test, preferred to eat the food they experienced in the mum's feeding area
      instead of what they experienced in their own feeding area. The fitness of such
      behaviour in more natural situations is discussed. 

PMID- 24895910
TI  - Reinforcer specificity of the suppression of instrumental performance on a non
      contingent schedule.
AB  - Hungry rats were trained to press one lever for a sucrose solution and another
      for food pellets on a concurrent schedule. The contingency between lever pressing
      and reinforcement was then reduced by delivering either free sucrose solution or
      free food pellets. The non-contingent schedule resulted in a greater reduction of
      pressing on the lever associated with the contiguous reinforcer that was the same
      as the free reinforcer. This finding suggests that the reduction in instrumental
      performance under a non-contingent schedule cannot be attributed solely to the
      development of competing responses. 

PMID- 24895911
TI  - How sticklebacks learn to avoid dangerous feeding patches.
AB  - Three-spined sticklebacks from sites with a high and a low predation risk were
      subjected to a passive avoidance test using a simulated attack from an overhead
      predator to provide negative reinforcement. All the subjects learned to avoid a
      feeding patch that had been strongly preferred when they received a simulated
      predatory attack whenever they entered this patch. The fish varied in the way in
      which they learned this task, in how quickly they did so and in the cues used to
      discriminate between the safe and the dangerous feeding patch. Some of this
      variation is related to the predation risk of their site of origin. 

PMID- 24895912
TI  - Highly selective separation of carbon dioxide from nitrogen and methane by
      nitrile/glycol-difunctionalized ionic liquids in supported ionic liquid membranes
      (SILMs).
AB  - Novel difunctionalized ionic liquids (ILs) containing a triethylene glycol
      monomethyl ether chain and a nitrile group on a pyrrolidinium or imidazolium
      cation have been synthesized and incorporated into supported ionic liquid
      membranes (SILMs). These ILs exhibit ca. 2.3 times higher CO2/N2 and CO2/CH4 gas
      separation selectivities than analogous ILs functionalized only with a glycol
      chain. Although the glycol moiety ensures room temperature liquidity of the
      pyrrolidinium and imidazolium ILs, the two classes of ILs benefit from the
      presence of a nitrile group in different ways. The difunctionalized pyrrolidinium
      ILs exhibit an increase in CO2 permeance, whereas the permeances of the
      contaminant gases rise negligibly, resulting in high gas separation
      selectivities. In the imidazolium ILs, the presence of a nitrile group does not
      always increase the CO2 permeance nor does it increase the CO2 solubility, as
      showed in situ by the ATR-FTIR spectroscopic method. High selectivity of these
      ILs is caused by the considerably reduced permeances of N2 and CH4, most likely
      due to the ability of the -CN group to reject the nonpolar contaminant gases.
      Apart from the CO2 solubility, IL-CO2 interactions and IL swelling were studied
      with the in situ ATR-FTIR spectroscopy. Different strengths of the IL-CO2
      interactions were found to be the major difference between the two classes of
      ILs. The difunctionalized ILs interacted stronger with CO2 than the glycol
      functionalized ILs, as manifested in the smaller bandwidths of the bending mode
      band of CO2 for the latter. 

PMID- 24895913
TI  - miR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia.
AB  - The NOS (nitric oxide synthase) inhibitor ADMA (asymmetric dimethylarginine)
      contributes to the pathogenesis of pulmonary hypertension. Reduced levels of the
      enzymes metabolizing ADMA, dimethylarginine dimethylaminohydrolases (DDAH1 and
      DDAH2) and increased levels of miR-21 are linked to disease pathology, but the
      mechanisms are not understood. In the present study we assessed the potential
      role of miR-21 in the regulation of hypoxia-induced changes in ADMA metabolism in
      vitro and in vivo. Hypoxia inhibited DDAH1 and DDAH2 expression and increased
      ADMA levels in cultured human pulmonary endothelial cells. In contrast, in human
      pulmonary smooth muscle cells, only DDAH2 was reduced whereas ADMA levels
      remained unchanged. Endothelium-specific down-regulation of DDAH1 by miR-21 in
      hypoxia induced endothelial dysfunction and was prevented by overexpression of
      DDAH1 and miR-21 blockade. DDAH1, but not DDAH2, mRNA levels were reduced,
      whereas miR-21 levels were elevated in lung tissues from patients with pulmonary
      arterial hypertension and mice with pulmonary hypertension exposed to 2 weeks of
      hypoxia. Hypoxic mice treated with miR-21 inhibitors and DDAH1 transgenic mice
      showed elevated lung DDAH1, increased cGMP levels and attenuated pulmonary
      hypertension. Regulation of DDAH1 by miR-21 plays a role in the development of
      hypoxia-induced pulmonary hypertension and may be of broader significance in
      pulmonary hypertension. 

PMID- 24895915
TI  - Postoperative delirium: disconnecting the network?

PMID- 24895914
TI  - Closing the pore on reperfusion injury: myocardial protection with cyclosporine.

PMID- 24895916
TI  - Replication to advance science: changes in ANESTHESIOLOGY.

PMID- 24895917
TI  - Comparison of chronic suppurative otitis media in rural and urban primary school
      children in Bangladesh.
AB  - OBJECTIVES: To compare chronic suppurative otitis media prevalence in rural and
      urban primary school children in Bangladesh, and to determine its relationship
      with specific sociodemographic factors. METHODS: In this cross-sectional survey,
      681 rural primary school children from Shibpur upazilla, Narsingdi district, and
      964 urban primary school children from Dhaka Metropolitan City, underwent an ENT
      check-up by doctors trained in ENT. Their parents or guardians were interviewed
      with regard to their sociodemographic status and other related issues using a pre
      tested protocol. RESULTS: In this study, 6.02 per cent of the rural primary
      school children and 2.07 per cent of the urban primary school children had
      chronic suppurative otitis media. (Overall, 3.71 per cent of the children had the
      disorder.) The disorder was slightly more prevalent among girls than boys in both
      rural (6.05 vs 5.98 per cent) and urban (2.33 vs 1.82 per cent) communities.
      There was a significant association between the presence of chronic suppurative
      otitis media in children and: parents' or guardians' occupation and their annual
      income, housing type, family size, maternal education, and bathing habit.
      CONCLUSION: Improvement of associated sociodemographic factors would reduce the
      prevalence and resultant complications of chronic suppurative otitis media in
      primary school children in developing countries.

PMID- 24895918
TI  - Display vigour and subsequent fight performance in the siamese fighting fish,
      betta splendens.
AB  - The display of 24 individual male Siamese fighting fish to an unresponsive
      stimulus conspecific was measured, and the fish were then placed together in
      pairs. For 11 of the 12 pairs, the outcome of the aggressive interaction which
      ensued was predicted by the gill cover erection durations obtained in the pre
      fight isolate tests. The implications of this result for theories of display
      function are discussed. 

PMID- 24895919
TI  - Modification of a stimulus-reinforcer interaction by blocking.
AB  - With tone-light compound-stimulus training, light will gain control of responding
      under an appetitive schedule while tone will gain considerable control with
      avoidance training. The present experiment sought to determine whether this
      stimulus-reinforcer interaction could be modified by a "blocking" procedure.
      Initially, one group of rats was trained to respond for food in tone while tone
      off was food free, and a second group was trained to avoid shock in light while
      light-out was shock free. Following attainment of a 10:1 discrimination ratio,
      food and avoidance schedules were signaled, for the respective groups, by a tone
      light compound stimulus. An element test demonstrated that the blocking procedure
      overcame the stimulus-reinforcer interaction previously reported with rats in
      both the appetitive and avoidance groups. Contrary to previous stimulus
      reinforcer interaction research, here, the tone, rather than the light,
      controlled responding after food training while the light, rather than the tone,
      controlled responding after avoidance training. These results obey predictions
      from associative theory. The current experiment is also the first demonstration
      of blocking within an instrumental avoidance procedure. 

PMID- 24895920
TI  - Fixed interval and fixed time treadle pressing in the pigeon: A comparison with
      FI and FT keypecking.
AB  - Experiment I used non-naive pigeons having previously performed on both
      keypecking and treadlepressing Fixed Interval schedules. In condition IT,
      treadlepressing was reinforced on successive Fixed Interval 60 seconds, Fixed
      Time 60 seconds and Fixed Interval 60 seconds schedules. Subsequently (condition
      IK), the same subjects pecked a key on an identical schedule sequence (FI60,
      FT60, FI60). In Experiment II, separate groups of naive subjects were assigned
      either to treadlepressing (condition IIT) or keypecking (condition IIK) and to
      the same schedule sequence (FI60, FT60, FI60). Treadle pressing and keypecking
      decreased greatly in Fixed Time schedules. Curvature indices, pauses and running
      rates were less sensitive than response rates to the switching from one schedule
      to the other. Experiments I and II yielded similar results, experimental history
      accounting only for minor differences. The results were discussed in relation to
      interspecies differences in the temporal regulation of behavior and operant
      versus respondent control of the response and schedule-induced behaviour. 

PMID- 24895921
TI  - Exposure of embryos to an aromatization inhibitor increases copulatory behaviour
      of male quail.
AB  - This experiment examined the possibility that endogenous embryonic androgen
      contributes to sexual differentiation of behaviour in male or female quail
      (Coturnix coturnix japonica ), and that it does so via aromatization (conversion
      to oestrogen). Eggs were injected on day 9 of incubation with oil or ATD (an
      aromatization inhibitor). As adults, males and females were exposed to short
      days, injected with testosterone propionate, tested for male-typical behaviour,
      then injected with oestradiol benzoate and tested for female-typical receptivity.
      ATD increased the level of male-typical copulatory behaviour in males. Male
      typical behaviour in females was not affected, nor was female-typical behaviour
      in either sex. Thus normal male quail are actually slightly demasculinized by
      their own androgen during embryonic development, and this process is mediated by
      aromatization. 

PMID- 24895922
TI  - Intrusion of stereotyped responding in pigeon spatial memory tasks.
AB  - Pigeons appear predisposed to respond in stereotyped manners in multi-item
      spatial memory tasks in which the items are simultaneously presented. We
      discovered this when we attempted to study primacy and recency serial position
      effects using a delayed matching of key location task (Experiment 1) and when we
      attempted to develop a keypack analog of the radial-arm maze task (Experiment 4).
      In Experiment 1 matching accuracy for first-pecked sample was above chance,
      approximately chance for the second-pecked sample, and below chance for the third
      pecked sample. Experiments 2 and 3 showed that the results of Experiment 1 were
      due to "superstitious" stereotyped responding: When pigeons were allowed to
      respond to two or three keys in any order and then respond to the same keys
      again, they responded in the same order on the second occasion. In Experiment 4,
      the pigeons successfully avoided pecking previously-pecked keys but did so by
      pecking the keys in a fixed sequence. 

PMID- 24895923
TI  - Effects of morphine in different strains of paradise fish (Macropodus opercularis
      L.): An ethopharmacological analysis.
AB  - The behavioural effects of morphine on random bred Macropodus opercularis , five
      strains of this species of fish, and the closely related subspecies M.
      opercularis concolor , were assessed by an ethopharmacological analysis based on
      the study of different active and passive behavioural units. The results showed
      that morphine In general these findings stress out the importance of
      ethopharmacological studies for assessing qualitative behavioural differences
      which may be related to genetically-modulated neurobiological differences. 

PMID- 24895924
TI  - Social conditioning and dominance in male betta splendens.
AB  - To determine whether social conditioning modifies relative dominance in the
      Siamese fighting fish (Betta splendens ), individual fish were matched for gill
      cover erection frequency (GCEF) to a mirror. One member of each pair experienced
      a series of four winning encounters (dominants) while the other of the pair
      experienced four losing encounters (subordinates). After the fighting experience,
      matched pairs were placed together and aggressive responses of both fish were
      recorded. Fish experiencing wins displayed significantly more and were more
      aggressive than fish experiencing losses which showed significantly higher levels
      of avoidance. However, no change in mirror GCEF occurred as a result of
      differential experience. 

PMID- 24895925
TI  - Sexual selection in gallus: Effects of morphology and dominance on female spatial
      behavior.
AB  - Sexual selection has received a great deal of attention from field and laboratory
      researchers for over a century, but hard evidence of female choice of mates in
      mixed-sex groups remains scarce. Dominant males typically mate much more often
      than subordinants but evidence that females "choose" such males is elusive. In
      Gallus , which includes junglefowl and their domestic fowl descendants, females
      stay near and mate with dominant, territorial males. We demonstrate here that
      Gallus females in mixed-sex flocks who have no information about the social
      dominance status of males orient to, approach and stay near males with larger
      than average combs whereas females which do not have information about male
      dominance orient toward and stay near high ranking males. We verify that comb
      size correlates with male social rank. Hence, Gallus females do actively respond
      to "high quality" males; they apparently identify such males by male physical
      characteristics and, if available, information concerning male-male interactions.

PMID- 24895926
TI  - The time course of attack priming effects in female golden hamsters.
AB  - In two experiments using different procedures we have found that attack latency,
      having been reduced by a previous priming attack, returns to baseline levels over
      a 24 hr period. In both experiments an unexpected, transient increase in attack
      latency occured 2 hr postpriming. The procedure of the second experiment
      precludes the possibility that this is a circadian effect. There were no
      cumulative effects of successive priming attacks suggesting that, under the
      conditions of these experiments, each attack "resets" the animals' aggressive
      state. The effects of a single brief agonistic encounter are substantial and
      persistent enough to be involved in such phenomena as the escalation and
      redirection of aggression observed in field studies. 

PMID- 24895927
TI  - Social stress, mortality and aggression in colonies and burrowing habitats.
AB  - High mortality was found within six mixed-sex groups of Long-Evans rats living in
      burrowing habitats with 58% of subordinate males dying within 4 mo. of group
      formation. By contrast, no subordinate deaths occured during this time in six
      identical adult groups(3 males and 3 females) housed in similar (1 m square)
      colony cages without burrows. Although aggression against intruders was also much
      greater in habitats than colonies --through 400 days postformation--subordinate
      deaths did not appear to result from direct physical injury. It seems that
      mimicing key features of the rat's environment enhances intermale conflict and
      social stress, even while providing partial protection from biting attack. Behav.
      Proc.: 

PMID- 24895928
TI  - New place and new object reactions in the brown spiny mouse, Mus platythrix
      Bennett.
AB  - The behavioural response of the brown spiny mouse, Mus platythrix Bennett to new
      place and new object was studied in a plus (+) maze. The new place reaction was
      observed by allowing the mice to access an area which had previously been not
      exposed to them and the new object reaction was studied by introducing a change
      at the feeding point. The experiment suggested new place philia and new object
      philia in this species. 

PMID- 24895932
TI  - Stereotypies in ranch mink: the effect of genes, litter size and neighbours.
AB  - This study was conducted on two generations of ranch mink to test the hypothesis
      that the behaviour of stereotypy (SY) in ranch mink is subject to heredity. Two
      groups of 14 females were selected as low stereotyping and high stereotyping
      individuals as extremes from 61 females. They were observed in two periods, one
      before mating and one after mating. The selection was based upon four SY
      frequencies of which two excluded the parameter Pendling. The kits of the two
      groups of females were also observed and the difference in level of SY between
      the two groups of mothers was upheld in the next generation. Combined with the
      finding of a positive, though not significant, correlation between the SY
      frequency of mothers and the mean frequency of litters this indicated a genetic
      effect upon the level of SY. A positive correlation between the litter size and
      the mean SY level of the litters was found. Though not significant it was
      considered important. A neighbour effect on the SY level in farm mink could not
      be found. All these results were obtained regardless of whether or not Pendling
      was incorporated into the SY frequency indicating that Pendling is induced by the
      same factors as other SYs. 

PMID- 24895933
TI  - Influence of degree of food restriction, age and time of day on behaviour of
      broiler breeder chickens.
AB  - Six groups of 25 growing female broiler breeder chickens in pens were fed either
      on a commercial restricted ration (R), twice that amount (2R), or ad libitum
      (AL). R and 2R birds were fed daily at 09.00 h and ate all their food in < 15
      min. Behaviour was observed systematically at three times of day (once before and
      twice after feeding time) at 6,9,12, 15 and 18 weeks of age. In general,
      restricted-fed (R and 2R) birds were much more active than AL birds. There were
      significant (P < 0.05) effects of feeding treatment on all activities recorded
      except preening and pecking at the empty feeder (R and 2R birds only); age
      affected drinking, preening, walking, standing and sitting; and time of day
      affected all activities except feeding (AL birds only). Activities that appeared
      to reflect feeding motivational state closest were walking before feeding time,
      and drinking, pecking floor litter and sitting after feeding time. AL birds
      (only) panted for about a third of the time at moderate ambient temperatures, and
      changes in their behaviour with age were thermoregulatory. It is proposed that
      activities of restricted-fed animals that are dominant after feeding time may be
      substitutable and have common causation and consequences. Distinction between
      stereotyped and non-stereotyped behaviour in this context may therefore be
      misleading. 

PMID- 24895934
TI  - Reproductive activation of virgin female prairie voles (Microtus ochrogaster) by
      paired and unpaired males.
AB  - Virgin female Microtus ochrogaster were exposed to paired and unpaired unfamiliar
      adult males in semi-natural arenas. Although females were reproductively
      activated by both types of males, more than twice as many were activated by
      unpaired (51.6%) as by paired (18.2%) males. Our results suggest that, in natural
      populations of prairie voles, the proportion of philopatric females becoming
      reproductive is related to the abundance of unpaired males within the population.

PMID- 24895935
TI  - Range effects in transient and maintained generalization gradients.
AB  - In three experiments pigeons were trained to discriminate visual flicker rate
      stimuli. The stimulus set was varied so that the effects of overall stimulus
      range and border separation between positive and negative stimuli could be
      assessed. Experiments 1 and 2 showed that transient generalization gradients were
      lower in height and flatter with increases in either border separation or overall
      stimulus range. Border separation and overall range interacted in that the effect
      of range was greatest with relatively greater border stimulus separation.
      Experiment 3 showed that increased overall stimulus range reduced the magnitude
      of positive dimensional contrast in maintained gradients. Flattening of the
      maintained gradient with increases in stimulus range was similar to flattening of
      post-discrimination gradients found in Experiments 1 and 2. The results from all
      experiments indicate that increases in overall stimulus range do not decrease
      discriminability of unchanged stimulus values. Instead, increases in stimulus
      range may increase the variability of response or criterial factors in
      discrimination. 

PMID- 24895936
TI  - Spontaneous exploration, response plus position learning and hippocampal mossy
      fibre distribution: A correlational study.
AB  - Forty-eight mice from twelve isogenic groups were tested in two different
      behavioral tests. The first test was a non-reinforced exploration of a Y-maze and
      the second was a response plus position learning followed by reversal learning in
      a T-maze. Behavioral results were correlated with the size of the area occupied
      by the various mossy fibre synaptic sub-fields in the hippocampus as revealed by
      Timm staining. The analysis of results showed that mice with a large
      suprapyramidal mossy fibre area tended to use a somewhat rigid motor response
      strategy during the initial exploration of the Y-maze, that they easily learned
      the response plus position task in the T-maze, but proved unable to quickly
      inhibit that learned response during the reversal task. On the other hand, mice
      with a large intra-infrapyramidal synaptic field displayed greater ability to
      cope with a situation including novelty or constraint elements. 

PMID- 24895937
TI  - The determinants of postreinforcement pausing.
AB  - Pigeons typically pause following food presentation on schedules that program
      food at regular intervals. These postreinforcement pauses (prps) are a constant
      proportion of the interfood interval (IFI). Wynne and Staddon (1988) proposed one
      back linear waiting as an account for postreinforcement pausing, or waiting time,
      as they called it, on response-initiated-delay schedules. Moreover, they implied
      that the same process could account for the prp on all fixed-interval schedules.
      This study examined prp performance of pigeons on two chained schedules of
      reinforcement, one with cyclically-changing IFIs and one in which the IFI was
      constant. The results provide support for the linear waiting hypothesis and
      replicate the findings of Innis et al. (1993) who examined performance on similar
      chained schedules. 

PMID- 24895938
TI  - Agonistic behaviour and dominance relations of captive arctic foxes (Alopex
      lagopus) in Svalbard.
AB  - Agonistic behaviour and dominance relations were studied in three groups of
      arctic foxes (Alopex lagopus) on the western coast of Svalbard (79 degrees N):
      (1) Five 'tame' foxes (3??, 2??) kept in captivity for 9-26 months, (2) twenty
      two 'wild' foxes (11??, 11??) kept in captivity for 4 days to 3 weeks, and (3)
      free-living foxes. Experiments were started by introducing two foxes (n = 74
      dyads) into a large enclosure (360 m(2)), scoring winners and losers in a
      competition for food, calculating a dominance index (DI), and observing the
      frequency of 12 behaviours. DI was correlated with body size as measured by the
      length of a front foot, but not with body weight. Males dominated females more
      frequently than vice versa (P < 0.06). Tame foxes were more playful and less
      aggressive than wild foxes. Fighting was mostly restricted to chasing and
      following, and no injuries were seen. When considering all 12 behaviours no
      significant difference was found between winners and losers, males and females,
      larger and smaller, heavier and lighter foxes. However, winners were more
      frequently following and chasing (i.e. offensive), while losers more frequently
      behaved submissively. Ignoring (dominant) or evading (subordinate) behaviours
      were frequent, and no distinct display signalling high social status was found. 

PMID- 24895939
TI  - Electrochemical detection of p-ethylguaiacol, a fungi infected fruit volatile
      using metal oxide nanoparticles.
AB  - Nanoparticles of TiO(2) or SnO(2) on screen-printed carbon (SP) electrodes have
      been developed for evaluating their potential application in the electrochemical
      sensing of volatiles in fruits and plants. These metal oxide nanoparticle
      modified electrodes possess high sensitivity and low detection limit for the
      detection of p-ethylguaiacol, a fingerprint compound present in the volatile
      signature of fruits and plants infected with a pathogenic fungus Phytophthora
      cactorum. The electroanalytical data obtained using cyclic voltammetry and
      differential pulse voltammetry showed that both SnO(2) and TiO(2) exhibited high
      sensitivity (174-188 MUA cm(-2) mM(-1)) and low detection limits (35-62 nM) for p
      ethylguaiacol detection. The amperometric detection was highly repeatable with
      RSD values ranging from 2.48 to 4.85%. The interference studies show that other
      common plant volatiles do not interfere in the amperometric detection signal of p
      ethylguaiacol. The results demonstrate that metal oxides are a reasonable
      alternative to expensive electrode materials such as gold or platinum for
      amperometric sensor applications.

PMID- 24895940
TI  - Are H2S-trapping compounds pertinent to the treatment of sulfide poisoning?

PMID- 24895941
TI  - Intoxications of the new psychoactive substance 5-(2-aminopropyl)indole (5-IT): a
      case series from the Swedish STRIDA project.
AB  - CONTEXT: 5-(2-aminopropyl)indole (5-IT) is a new psychoactive substance (NPS;
      "legal high" or "research chemical") structurally related to indoleamines and
      substituted phenethylamines and implicated in several fatalities. We describe the
      clinical characteristics and results of laboratory investigations of 14
      analytically confirmed nonfatal cases of 5-IT intoxication within the Swedish
      STRIDA project. STUDY DESIGN: Observational case series of consecutive patients
      with admitted or suspected intake of NPS presenting to hospitals in Sweden in
      2012. PATIENTS AND METHODS: Blood and/or urine samples were collected from
      intoxicated patients presenting to emergency departments and intensive care units
      over the country. Analysis of NPS was performed using an LC-MS/MS multi-component
      method. Clinical data were collected when caregivers consulted the Poisons
      Information Centre and also retrieved from medical records. The severity of
      poisoning was graded retrospectively using the Poisoning Severity Score (PSS).
      RESULTS: Eleven male and three female patients (age: 21-53 years, median: 27)
      tested positive for 5-IT in 2012, all cases appearing in April-July. The 5-IT
      concentration in serum ranged between 0.015 and 0.59 MUg/mL (median: 0.22; n = 8)
      and in urine between 0.005 and 24.7 MUg/mL (median: 5.95; n = 12). Five
      intoxications were indicated to be caused by 5-IT alone, whereas additional
      psychoactive substances were detected in the other nine cases. Six (43%) of
      fourteen cases were graded as severe (PSS 3), five (36%) as moderate (PSS 2), and
      three (21%) as minor (PSS 1) poisonings. In the severe cases, agitation,
      hallucinations, dilated pupils without light reaction, tachycardia, hypertension,
      hyperthermia, myoclonus, muscle rigidity, arrhythmias, seizures, rhabdomyolysis,
      and/or renal failure were noted. CONCLUSIONS: The results demonstrated that
      severe clinical toxicity was commonly present in patients with analytically
      confirmed 5-IT exposure. The clinical features are consistent with a
      sympathomimetic toxidrome, and some patients also displayed symptoms associated
      with serotonin toxicity.

PMID- 24895942
TI  - Power and sample size for randomized phase III survival trials under the Weibull
      model.
AB  - Two parametric tests are proposed for designing randomized two-arm phase III
      survival trials under the Weibull model. The properties of the two parametric
      tests are compared with the nonparametric log-rank test through simulation
      studies. Power and sample size formulas of the two parametric tests are derived.
      The sensitivity of sample size under misspecification of the Weibull shape
      parameter is also investigated. The study can be designed by planning the study
      duration and handling nonuniform entry and loss to follow-up under the Weibull
      model using either the proposed parametric tests or the well-known nonparametric
      log-rank test. 

PMID- 24895943
TI  - Toe flexor strength and foot arch height in children.
AB  - PURPOSE: The aim of this study was to investigate the muscle strength and arch
      height of the foot in the standing position and the relations between these
      indices and physical performances involving the lower limbs in children. METHODS:
      A total of 301 elementary school children (third grade: n = 158, age = 8.6 +/-
      0.5 yr; fifth grade: n = 143, age = 10.6 +/- 0.5 yr; means +/- SD) participated.
      The maximal isometric toe flexor strength (TFS) in the standing position was
      measured using a toe flexor dynamometer. Foot arch height was assessed as the
      distance between the navicular tuberosity of the foot and the floor in the
      standing position, and foot arch height relative to the foot length was
      represented by the foot arch index (FAI). For physical performance involving the
      lower limbs, 50-m sprint, standing broad jump, repeated side step, and rebound
      jump were measured. RESULTS: There were no significant correlations between TFS
      and FAI and between relative TFS (relative TFS = TFS/body mass) and FAI. Relative
      TFS was significantly correlated with all physical performance tests. No
      significant correlations among FAI and physical performances were found, except
      for rebound jump ability in fifth graders. After multiple regression analyses
      adjusting for gender and body mass, TFS was the only significant correlating
      factor for all physical performances involving the lower limbs. CONCLUSIONS: This
      study showed that TFS was associated with enhancement of some measures of lower
      limb physical performance in children. These results suggest that foot function
      should be evaluated with both the muscle strength and arch height of the foot in
      children.

PMID- 24895944
TI  - Novel zirconium nitride and hydroxyapatite nanocomposite coating: detailed
      analysis and functional properties.
AB  - A new type of high-quality zirconium nitride (ZrN) and hydroxyapatite (HA)
      bionanocomposite was prepared by radio-frequency (RF) magnetron sputtering for
      biomedical applications. Detailed analysis of this composite coating revealed
      that a higher substrate temperature (ST) (>300  degrees C) increased its
      crystallinity, uniformity, and functional properties. This nanocomposite showed
      some encouraging functional properties. Mechanical analyses of the nanocomposite
      showed improved hardness, modulus, and wear resistance, which were found to be
      due to the increasing volume fraction of ZrN at higher ST. Biomineralization and
      in vitro cell analysis revealed increased weight gain and enhanced cell activity
      with increased substrate temperature. Overall, the results of the present study
      indicate that this nanocomposite coating could become a promising alternative for
      biomedical applications. 

PMID- 24895945
TI  - Thermal insulation for preventing inadvertent perioperative hypothermia.
AB  - BACKGROUND: Inadvertent perioperative hypothermia occurs because of interference
      with normal temperature regulation by anaesthetic drugs and exposure of skin for
      prolonged periods. A number of different interventions have been proposed to
      maintain body temperature by reducing heat loss. Thermal insulation, such as
      extra layers of insulating material or reflective blankets, should reduce heat
      loss through convection and radiation and potentially help avoid hypothermia.
      OBJECTIVES: To assess the effects of pre- or intraoperative thermal insulation,
      or both, in preventing perioperative hypothermia and its complications during
      surgery in adults. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 2), MEDLINE, OvidSP
      (1956 to 4 February 2014), EMBASE, OvidSP (1982 to 4 February 2014), ISI Web of
      Science (1950 to 4 February 2014), and CINAHL, EBSCOhost (1980 to 4 February
      2014), and reference lists of articles. We also searched Current Controlled
      Trials and ClinicalTrials.gov. SELECTION CRITERIA: Randomized controlled trials
      of thermal insulation compared to standard care or other interventions aiming to
      maintain normothermia. DATA COLLECTION AND ANALYSIS: Two authors extracted data
      and assessed risk of bias for each included study, with a third author checking
      details. We contacted some authors to ask for additional details. We only
      collected adverse events if reported in the trials. MAIN RESULTS: We included 22
      trials, with 16 trials providing data for some analyses. The trials varied widely
      in the type of patients and operations, the timing and measurement of
      temperature, and particularly in the types of co-interventions used. The risk of
      bias was largely unclear, but with a high risk of performance bias in most
      studies and a low risk of attrition bias. The largest comparison of extra
      insulation versus standard care had five trials with 353 patients at the end of
      surgery and showed a weighted mean difference (WMD) of 0.12 oC (95% CI -0.07 to
      0.31; low quality evidence). Comparing extra insulation with forced air warming
      at the end of surgery gave a WMD of -0.67 oC (95% CI -0.95 to -0.39; very low
      quality evidence) indicating a higher temperature with forced air warming. Major
      cardiovascular outcomes were not reported and so were not analysed. There were no
      clear effects on bleeding, shivering or length of stay in post-anaesthetic care
      for either comparison. No other adverse effects were reported. AUTHORS'
      CONCLUSIONS: There is no clear benefit of extra thermal insulation compared with
      standard care. Forced air warming does seem to maintain core temperature better
      than extra thermal insulation, by between 0.5 oC and 1 oC, but the clinical
      importance of this difference is unclear.

PMID- 24895946
TI  - The gifts of summer.

PMID- 24895947
TI  - Open intensive care units: a global challenge for patients, relatives, and
      critical care teams.
AB  - AIM: The aims of this study were to describe the current status of intensive care
      unit (ICU) visiting hours policies internationally and to explore the influence
      of ICUs' open visiting policies on patients', visitors', and staff perceptions,
      as well as on patients' outcomes. METHODS: A review of the literature was done
      through MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health
      Literature (CINAHL) databases. The following keywords were searched: "visiting,"
      "hours," "ICU," "policy," and "intensive care unit." Inclusion criteria for the
      review were original research paper, adult ICU, articles published in the last 10
      years, English or Italian language, and available abstract. RESULTS: Twenty-nine
      original articles, mainly descriptive studies, were selected and retrieved. In
      international literature, there is a wide variability about open visiting
      policies in ICUs. The highest percentage of open ICUs is reported in Sweden
      (70%), whereas in Italy there is the lowest rate (1%). Visiting hours policies
      and number of allowed relatives are variable, from limits of short precise
      segments to 24 hours and usually 2 visitors. Open ICUs policy/guidelines
      acknowledge concerns with visitor hand washing to prevent the risk of infection
      transmission to patients. Patients, visitors, and staff seem to be inclined to
      support open ICU programs, although physicians are more inclined to the
      enhancement of visiting hours than nurses. DISCUSSION: The percentages of open
      ICUs are very different among countries. It can be due to local factors, cultural
      differences, and lack of legislation or hospital policy. There is a need for more
      studies about the impact of open ICUs programs on patients' mortality, length of
      stay, infections' risk, and the mental health of patients and their relatives.

PMID- 24895948
TI  - Use of a 90-minute protocol to evaluate patients presenting to the emergency
      department with chest pain: a case study.
AB  - Frustration with emergency department wait times may contribute to patient delays
      in seeking care for subsequent episodes of chest pain and lower patient
      satisfaction ratings. In response to patient feedback and the dissemination of
      new knowledge, the existing emergency chest pain protocol was updated to include
      point-of-care laboratory testing and evaluation at baseline and 90 minutes. A
      case study was utilized to illustrate implementation of this protocol in the
      management of a patient presenting to the emergency department with chest pain.

PMID- 24895949
TI  - Reducing physical restraint use in alcohol withdrawal patients: a literature
      review.
AB  - Alcohol withdrawal patients experience symptoms ranging from mild anxiety and
      disorientation to severe agitation and hallucinations. The most critical of these
      patients are treated in intensive care units. Physical restraints are often
      required to maintain patient safety until symptoms resolve. The use of physical
      restraints is contradictory to nursing values and is unsupported by evidenced
      based literature. A literature review was conducted to see what, if any,
      alternatives have been tested to improve patient care for this complicated
      patient population.

PMID- 24895950
TI  - Enhancing critical thinking in clinical practice: implications for critical and
      acute care nurses.
AB  - The complexity of patients in the critical and acute care settings requires that
      nurses be skilled in early recognition and management of rapid changes in patient
      condition. The interpretation and response to these events can greatly impact
      patient outcomes. Nurses caring for these complex patients are expected to use
      astute critical thinking in their decision making. The purposes of this article
      were to explore the concept of critical thinking and provide practical strategies
      to enhance critical thinking in the critical and acute care environment.

PMID- 24895952
TI  - Compassion fatigue, moral distress, and work engagement in surgical intensive
      care unit trauma nurses: a pilot study.
AB  - Preparation for replacing the large proportion of staff nurses reaching
      retirement age in the next few decades in the United States is essential to
      continue delivering high-quality nursing care and improving patient outcomes.
      Retaining experienced critical care nurses is imperative to successfully
      implementing the orientation of new inexperienced critical care nurses. It is
      important to understand factors that affect work engagement to develop strategies
      that enhance nurse retention and improve the quality of patient care. Nurses'
      experience of moral distress has been measured in medical intensive care units
      but not in surgical trauma care units, where nurses are exposed to patients and
      families faced with sudden life-threatening, life-changing patient
      consequences.This pilot study is a nonexperimental, descriptive, correlational
      design to examine the effect of compassion satisfaction, compassion fatigue,
      moral distress, and level of nursing education on critical care nurses' work
      engagement. This is a partial replication of Lawrence's dissertation. The study
      also asked nurses to describe sources of moral distress and self-care strategies
      for coping with stress. This was used to identify qualitative themes about the
      nurse experiences. Jean Watson's theory of human caring serves as a framework to
      bring meaning and focus to the nursing-patient caring relationship.A convenience
      sample of 26 of 34 eligible experienced surgical intensive care unit trauma
      nurses responded to this survey, indicating a 77% response rate. Twenty-seven
      percent of the nurses scored high, and 73% scored average on compassion
      satisfaction. On compassion fatigue, 58% scored average on burnout and 42% scored
      low. On the secondary traumatic stress subscale, 38% scored average, and 62%
      scored low. The mean moral distress situations subscale score was 3.4, which is
      elevated. The mean 9-item Utrecht Work Engagement Scale total score, measuring
      work engagement, was 3.8, which is considered low.Content analysis was used to
      identify themes of Role Conflict With Management/Rules, Death and Suffering,
      Dealing With Violence in the Intensive Care Unit, Dealing With Family,
      Powerlessness, Physical Distress, and Medical Versus Nursing Values. Additional
      themes identified were caring, helping families, long-time interdependent
      relationships of colleagues, and satisfaction in trauma nursing.As work
      engagement increased, compassion satisfaction significantly increased, and
      burnout significantly decreased. Results of this study support moral distress as
      a clinically meaningful issue for surgical intensive care unit nurses. Moral
      distress scales were elevated, whereas work engagement scales were low. This
      finding was congruent with Lawrence's study and may reflect ongoing need for
      greater supports for experienced intensive care unit nurses, from both education
      and management. Future recommendations for research include examining the
      interaction of these variables in larger samples to examine additional
      explanatory factors as well as strategies for self-care, motivation, and behavior
      change.

PMID- 24895953
TI  - Comprehensive review of an accelerated nursing program: a quality improvement
      project.
AB  - BACKGROUND: Accelerated second-degree programs are designed to provide entry into
      baccalaureate nursing program for people who have achieved bachelor's degree in
      another field. These programs were often designed to respond to nursing shortages
      at local and national levels. Programs commonly use a cohort model and move
      students through an intensive structure combining classroom and clinical
      requirement with a 2-year period. The accelerated second-degree nursing program,
      Accelerated Entry Level to Nursing program at our small liberal arts college, was
      considered to be successful. The program had excellent graduation rates and
      National Council Licensure Examination for Registered Nurses pass rates,
      indicating that the program was preparing the graduate to thrive in the practice
      setting. The program had been in existence for more than 7 years, with highly
      competitive admissions and high student satisfaction. OBJECTIVE/AIM: The
      objective of this study was to provide a quality improvement assessment process
      to capture quantitative and qualitative information about the graduates. This
      information would be used to inform our own nursing education department and
      would provide metrics and information for nurse leaders regarding the rigor of
      these programs and the potential of graduates. DESIGN: Continuous quality
      improvement is a vital component in nursing education as well as in the clinical
      setting. With this in mind, a comprehensive review was undertaken by the nursing
      faculty during the eighth year of the highly successful accelerated nursing
      program in a small liberal arts college. This quality improvement project was
      designed to review existing metrics and to collect additional data through survey
      and focus groups in order to capture experiences of the program graduates.
      PARTICIPANTS/SUBJECTS: Graduates of the accelerated program from 2005 to 2011
      were included in this study. Faculty who teach in the program participated in
      focus groups. RESULTS: From 2005 to 2011, there have been a total of 196
      graduates in 8 cohorts; 194 surveys were sent via e-mail to graduates with a
      return rate of 62 (32%). Regarding overall satisfaction with the program, 75% of
      the 53 respondents who answered this question were either very satisfied or
      extremely satisfied. The other 25% were satisfied. No respondents indicated that
      they were dissatisfied. More than three-fourths of the respondents indicated that
      the cost of the program was reasonable. Only 11% of the 55 respondents indicated
      that the clinical time in the program was sufficient. Graduates from 2005 to 2009
      (n = 34) are mostly employed at major Boston teaching medical centers in acute
      and intensive care settings. Programmatic recommendations from the focus groups
      included offering an optional 100-hour practicum to expose students to more
      clinical experiences in the acute care settings, increasing the credits for
      Nursing Care of Older Adults from 1 to 2, and providing academic support for
      English as second language/minority students. Curricular recommendations included
      increasing the time allocation for simulations, moving pediatrics to the summer
      semester, and spreading pharmacology between 2 courses. CONCLUSION: Program
      review is an important component of continuous quality improvement in the
      academic setting. This review provided information that indicated although a
      program can be highly successful on many parameters, there is always room for
      improvement. In educating the second-degree student, the nursing profession
      benefits from the addition of professionals from other disciplines adding
      professional depth and richness to the profession. In addition, including the
      voice of the nurse after graduation provided insightful direction for some
      clinical and curriculum changes.

PMID- 24895954
TI  - Assessing and addressing moral distress and ethical climate, part 1.
AB  - BACKGROUND: There is minimal research exploring moral distress and its
      relationship to ethical climate among nurses working in acute care settings.
      OBJECTIVES: Objectives of the study were to explore moral distress, moral
      residue, and perception of ethical climate among registered nurses working in an
      academic medical center and develop interventions to address study findings.
      METHOD: A mixed-methods design was used. Two versions of Corley and colleagues'
      Moral Distress Scale, adult and pediatric/neonatal, were used in addition to
      Olson's Hospital Ethical Climate Survey. Participants were invited to respond to
      2 open-ended questions. This article reports the results for those nurses working
      in adult acute and critical care units. RESULTS: The sample (N = 225) was
      predominantly female (80%); half held a bachelor of science in nursing or higher,
      were aged 30 to 49 years, and staff nurses (77.3%). The mean item score for moral
      distress intensity ranged from 3.79 (SD, 2.21) to 2.14 (SD, 2.42) with mean item
      score frequency ranging from 2.86 (SD, 1.88) to 0.23 (SD, 0.93). The mean score
      for total Hospital Ethical Climate Survey was 94.39 (SD, 18.3) ranging from 23 to
      130. Qualitative comments described bullying, lateral violence, and retribution.
      DISCUSSION: Inadequate staffing and perceived incompetent coworkers were the most
      distressing items. Almost 22% left a previous position because of moral distress
      and perceived the current climate to be less ethical compared with other
      participants. Findings may potentially impact nurse retention and recruitment and
      negatively affect the quality and safety of patient care. Interventions developed
      focus on the individual nurse, including ethics education and coping skills,
      intraprofessional/interprofessional approaches, and administrative/policy
      strategies.

PMID- 24895955
TI  - Mechanical ventilation and the role of saline instillation in suctioning adult
      intensive care unit patients: an evidence-based practice review.
AB  - BACKGROUND: Saline instillation in suctioning mechanically ventilated patients
      remains a common practice in the intensive care unit (ICU). Many respiratory
      therapists and nurses are using saline with suctioning without an adequate
      knowledge of the current evidence-based research to guide this practice.
      OBJECTIVES: The purpose of this study was to determine if this routine method is
      beneficial or harmful to the patients and provide evidence-based practice
      recommendations that will serve as a guide for practice. METHODS: This is a
      comprehensive review on the use of saline instillation in suctioning mechanically
      ventilated adult ICU patients. Database such as CINAHL, MEDLINE, Cochrane,
      PsycINFO, and national guidelines are extracted for the review of literature. The
      study population consists of patients 18 years or older, who are intubated or
      have a tracheostomy in place, requiring mechanical ventilation, and who are
      admitted in the ICU. RESULTS: Although most of the evidence suggests not to use
      saline when suctioning, there are various limitations to the studies such as
      small sample size, settings, inconsistencies in data collection, or not enough or
      outdated research clinical trials, which calls for further studies. CONCLUSION:
      This study does not support the use of saline instillation when suctioning an
      artificial airway. Further clinical trials are crucial to effectively determine
      if saline instillation use with suctioning an artificial airway is deemed
      harmful, which can be strictly enforced as a mandatory clinical guideline for all
      hospitals to include in their standardized protocol to not use saline
      instillation with suctioning.

PMID- 24895958
TI  - Miracles in our midst.

PMID- 24895959
TI  - The organization of grooming in budgerigars.
AB  - Structural rules for grooming are examined in the budgerigar (Melopsittacus
      undulatus). Two types of bouts are found: short bouts with no predictable
      temporal pattern and long bouts with some degree of periodic occurrence.
      Transitions in long bouts are mostly based on anatomical proximity. Grooming
      movements cluster together according to function and body region. Evidence for
      hierarchical organization obtained by clustering is confirmed by the proportion
      of occurrence of movements in long and short bouts. Individual birds are similar
      enough on measures of occurrence, transition and hierarchica structure for
      pooling of subjects to be justified; this suggests that the organizational rules
      found here are to a large extent species-typical. 

PMID- 24895960
TI  - Behavioural and morphological dose-responses to testosterone and to 5alpha
      dihydrotestosterone in the castrated male Japanese quail.
AB  - Morphological and behavioural effects of testosterone (T) and of 5 alpha
      dihydrotestosterone (5alpha-DHT) injected daily for a 3-week period at dosages of
      0.5, 1, 5 and 10 mg for T and 1 and 5 mg for alpha-DHT were studied in the adult
      male castrated Japanese quail. Injections of 0.5 or 1.0 mg T produced only slight
      development of the cloacal gland while the other four treatments stimulated
      growth which reached maximal or submaximal values. Testosterone injections
      stimulated sexual activities; some such effects were also observed after
      treatment with 5alpha-DHT. Although both steroids elicited crowing, there were
      qualitative differences between quails given 5alpha-DHT and those given T and
      intacts. These differences were not due to the development of the sternotracheal
      (syringeal) muscles, the weights of which were increased and reached similar
      values in the 5alpha-DHT and T (5 and 10 mg) treated males. These results are
      discussed in the context of our present knowledge of the mechanisms of regulation
      of reproduction processes by testosterone and its metabolites in birds. 

PMID- 24895961
TI  - [Not Available].
AB  - Do the blind cave salamander Proteus and its epigean relative Necturus use the
      chemical sense in searching for prey? Proteus shows a significant, and Necturus
      only a weak, preference for water which passes living prey before entering a
      choice chamber. Prey which was frozen before the test also gave the same result
      in both species. However, with this immobilized prey the time for a decision in
      the test was much longer. The results of ten series of tests demonstrate the
      importance of chemoreception for prey detection in Proteus. The weaker reactions
      in Necturus can be explained probably by the different biotope. Six other series
      of tests have been conducted to show that our results are not influenced by
      stimuli relating to mechanoreception, thigmotaxis and rheotropism. 

PMID- 24895962
TI  - Responses to novelty in two inbred strains of mice and their F1 hybrids:
      Behaviour and brain biogenic amines.
AB  - Responses to novelty of two inbred strains of mice, C57BL/6JOrl (C) and A/JOrl
      (A) and their reciprocal F1 hybrids were recorded. The parental strains differed
      from each other: the C strain showed a preference for a novel environment and
      neophobic reactions to a novel object introduced into the familiar environment.
      The A mice were characterized by a preference for the familiar environment and
      lower neophobia towards the novel object. In addition, the C strain exhibited
      high and the A strain low locomotor activity. The reciprocal hybrids were
      identical in their major responses to the C strain. Neurochemical investigations
      indicated that the parental A strain showed a lower level of dopamine in the
      striatum and in the olfactory bulbs when compared with the C strain and the
      hybrid F1 C * A. 

PMID- 24895963
TI  - Aggressive behaviour in rats: Effects of winning or losing on subsequent
      aggressive interactions.
AB  - CPB-WE rats (WEzobs) tested for aggression against Tryon Maze Dull rats (S3s)
      were highly consistently defeated. In contrast, when tested against Wistars,
      these WEzobs become dominant. On the basis of these findings an experimental
      procedure was used in which the changes in agonistic responses as the result of
      experience of victory or defeat could be established. In addition, the effect of
      winning or losing was studied in subsequent encounters of winners and defeated
      WEzobs. The result of this experiment clearly indicate that a significant and
      relatively permanent behavioural inhibition develops in the defeated WEzobs which
      show less social initiative and aggression than the winners. The behavioural
      inhibition which is also seen in the spatial orientation of the animals within
      the test arena was still present after a 14 day interval. Significant loss of
      body weight was found in the losing animals. 

PMID- 24895964
TI  - Vasopressin accelerates appetitive discrimination learning and impairs its
      reversal.
AB  - Rats were trained in a semi-automated Y maze to find food at the end of the
      lighted arm. Those treated with 10 MU g lysine vasopressin, 90 min before
      training learned the response to a 9 10 correct choice criterion significantly
      faster than saline treated animals. There was no difference in rate of forgetting
      between the treatment groups, as evidenced by a retention test, 3 weeks after
      training. There was no direct effect of vasopressin on retrieval, since animals
      treated before the retention test performed at the same level as non treated
      animals. Finally, vasopressin impaired reversal from light to dark. In a second
      experiment, the acquisition facilitation seen in Exp. I was replicated, but there
      was no effect of the treatment on animals trained to dark SD. However, the
      impairment seen in Exp. I when vasopressin treated animals, trained to light,
      were reversed to dark, was replicated in this experiment in animals trained to
      dark and reversed to light. Previous demonstrations of vasopressin facilitation
      of learning and memory have, with few exceptions, relied on shock avoidance
      tasks. The present experiments demonstrate a reliable facilitation of appetitive
      learning by vasopressin. The fact that vasopressin impairs reversal may be due to
      an increased tendency to perseverate. 

PMID- 24895965
TI  - Social dominance relationships and spacing behavior of swine.
AB  - Dominance ranks were determined within each of eight pens of domestic swine,
      Susscrofa. Data on spacing and orientation of subjects were obtained from 16 mm
      time-lapse films and 35 mm overhead photographs with the aid of a digitizer
      assisted FORTRAN program, DISANGL 2. Dominance orders among subjects were
      relatively linear and stable. No pattern in pen location preferences (fixed
      space) was found but there were relationships between dominance rank and portable
      spacing patterns of the subjects. Distance to a nearest neighbor was the most
      important variable affecting the orientation of the swine, and the most dominant
      animal had a lesser tendency to face away from nearest neighbors at any
      particular distance and a greater tendency to space further from nearest
      neighbors than was the case for subordinates. The results of this study support
      the notion that social dominance provides a means by which a possible limited
      resource, such as personal space, may be differentially allocated to group
      members. 

PMID- 24895966
TI  - Temperature and immobility reaction in Rana temporaria.
AB  - Experiments were conducted on two groups of Rana temporaria acclimatized to 7
      degrees C and to 14 degrees C. Two hours prior to the experiments the animals
      were divided into six groups of 40 subjects each and placed in containers at
      temperatures of 5 degrees , 10 degrees , 15 degrees , 20 degrees , 25 degrees 
      and 30 degrees C. Frogs remained immobile for a shorter time in temperatures
      which differed little from those of acclimatization. It was concluded that the
      body temperature interferes with the duration of the immobility reaction. 

PMID- 24895967
TI  - Sexual experience and successful mating in staggerer mutant mice.
AB  - The behavioural study of the mutation staggerer has shown that under particular
      rearing conditions, the affected mice can live at least 19 months and can breed.
      Ten percent (10%) of males and more than 50% of females mated dmore than once. To
      intercross these it was necessary, most of the time, for them to have had
      previous sexual experience with a normal mouse. 

PMID- 24895969
TI  - Animal behavior: its development, ecology, evolution R.A. Wallace. Goodyear
      Publishing Co., Santa Monica, CA, 1979. 590 pp., US $19.95.

PMID- 24895975
TI  - Strain differences in mouse response to odours of predators.
AB  - Sexually mature male mice of three different strains (CD-1 outbred, CBA, and
      C57BI/6J inbred) were exposed in an arena to a small black cylinder (35 mm film
      container), filled with faeces of either a mouse predator (red fox, Vulpes
      vulpes) or a non-predator (rabbit, Oryctolagus cuniculus) during a 3 min test.
      Control animals were given an empty container. Locomotor activity and behavioural
      responses in the arena were scored. Hot-plate response (50 +/- 0.5 degrees C) was
      measured 15 min before and immediately after exposure to the odour. Responses to
      predators were found to be strain-specific. In CD-1 and C57 mice, latency of
      approach to the small cylinder increased while contacts with it decreased upon
      fox odour exposure. In CBA mice, fox odour caused an increase of defensive
      burying and sniffing, and a decrease of rearing. Odour exposure did not affect
      grooming, digging, or wall rearing in any of the strains. Hot-plate analgesia was
      also unaffected. The observed strain differences in the defensive response,
      interpreted as evolutionary adaptive anti-predatory strategies, seem to confirm
      the suggested origin of the two inbred strains used. 

PMID- 24895976
TI  - Directional consistency: Determinant of learned maze performance of five mice
      strains.
AB  - The heterogeneous mouse stocks HS/lbg and SABRA/HUC, and the inbred strains
      C57B1/6J, CBA/LAC, and BALB/crgl (a total of 88 mice), were employed in an
      investigation on strain differences in delayed spontaneous alternations (SA), and
      eight-arm-maze performance (EAM). Intact male mice were tested for SA at age 41
      days for two consecutive days, and for EAM at age 50-54 days, under conditions of
      water deprivation that commenced on day 43. The concept of EAM directional
      consistency (DC), proposed and defined here, was found highly related to EAM
      performance, and a better predictor of SA than EAM performance. Faceted smallest
      space analysis (FSSA), which provides a broad, simultaneous, perspective on the
      various maze behaviors observed (SA, EAM, DC), indicates that DC is both more
      closely related to SA and a more coherent concept than performance. The findings
      suggest that DC is a more elementary behavior, possibly related to different
      etiology than that of performance. Whilst in some studies EAM performance is
      viewed as spatial, here DC of mice suggest that, in fact, the animals are
      learning a set of rules. The results confirmed the superiority of the outbred HS
      over the inbred CBA, C57 and BALB, with SABRA occupying an intermediate position,
      and indicate that the medium performance strains rely on DC more than the others.

PMID- 24895977
TI  - Concurrent schedule control of monkey's observing during vigilance.
AB  - Experiment I exposed three crab-eating macaques to a vigilance task which
      required them to detect signals by holding down a lever and to report their
      occurrences by releasing the lever. Only those reporting responses which occurred
      within 1 s after onset of each signal were reinforced and letting go of the lever
      in the absence of the signals was punished by a blackout. Signals were presented
      according to concurrent variable-interval schedules and subjects could change
      over between alternatives by pressing another lever. All subjects showed frequent
      changeovers and time allocation of observing responses showed under-matching.
      matching. Experiment II exposed the subjects to a choice task which required
      continuous lever holding. Although all subjects showed undermatching, one of the
      subjects alternated less rapidly than in Experiment I. Experiment III exposed
      another monkey to a typical choice task in which a lever-pressing response was
      reinforced by a primary reinforcer and a vigilance task used in Experiment I. The
      subject alternated less rapidly and time allocation roughly mathced the
      reinforcement ratio in the choice task, whereas time allocation showed
      undermatching in the vigilance task. These findings suggested that performances
      under vigilance situations might differ from those under typical lever-pressing
      situations. 

PMID- 24895978
TI  - Learning new response sequences.
AB  - Four rats were required to press either a right or left lever to complete various
      three-response sequences. After extended exposure to a training sequence,
      subjects were shifted to a new target sequence. The new target sequences always
      differed from the previous sequence by the response required in the first or last
      position of the sequence. Subjects were repeatedly exposed to all possible
      combinations of training and new target sequences. Learning of new sequences
      occurred more rapidly when the change in the new target sequence was in the last
      position. Errors persisted longer in new sequences in which the change was in the
      first position. Extinction of the training sequence occured faster when the
      change was in the last position. Responses in the last position were considerably
      more sensitive to the shift to new target sequences than were responses in the
      first position. Even though response sequences may form new behavioral units from
      the training sequence, reinforcement and extinction acted differentially on the
      individual lever presses within new target sequences rather than on the sequences
      as a whole. These findings support the hypothesis that response strength is
      determined by contiguity to reinforcement. 

PMID- 24895979
TI  - Areas of concentrated use within seasonal ranges of Corsican mouflons: Importance
      of psychophysiological and ecological contexts in their modulation.
AB  - We studied the space use of mouflons (Ovis musimon) for more than four years in a
      population living in low Mediterranean mountains. The different behaviour of ewes
      and rams, which is related to social and spatial segregation outside the rut, has
      an effect on spatial use. Depending on the season, ecological or
      psychophysiological contexts influence the way in which the animals concentrate
      their activity in their range. The difference in spatial use between sexes is the
      most obvious during the rut and in winter. During the rut, rams exhibit a high
      degree of spatial instability while ewes continue as in summer, concentrating
      their activity in a restricted area. During winter, rams which have returned to
      their non-rut range exhibit spatial stability while females become more unstable.
      We suggest that spatial attachment of the two sexes is expressed differently and
      that the significance accorded by individuals to the psychophysiological and
      ecological contexts they live play on the significance of space and finally on
      spatial use. 

PMID- 24895980
TI  - Imitation in rats (Rattus norvegicus): The role of demonstrator action.
AB  - In a bidirectional control procedure, rats had their first opportunity to push a
      joystick immediately after observing, from an adjacent compartment, the joystick
      moving 50 times either to the right or to the left, with each movement signalling
      the delivery of inaccessible food. Half of these animals observed the joystick
      moving automatically, and half observed a conspecific demonstrator pushing the
      joystick. When they were given direct access to the joystick, the observers were
      rewarded for both left and right pushes. Rats that had observed the joystick
      moving through the action of a conspecific demonstrator showed a response bias in
      favour of the observed direction of joystick movement (Experiment 1), while rats
      that had observed the joystick moving automatically, either in the presence or
      absence of a passive conspecific, did not show observation-consistent responding
      (Experiments 1 and 2). These results apparently confirm that rats are capable of
      imitation or observational learning. 

PMID- 24895981
TI  - Gnawing and retrieval of inedible objects by Norway rats: Motivational
      interactions and habituatory effects.
AB  - The relation between gnawing and retrieval of inedible, partible objects (wooden
      blocks) by domestic Norway rats (Rattus norvegicus Berkenhout) was examined by
      manipulating the tendency to gnaw and testing subsequent retrieval. Experiments 1
      and 2 established that rats gnaw wooden blocks but do not ingest them even during
      food deprivation, and that gnawing declines (habituates) over days for most rats.
      In Experiment 3, food deprivation produced a decrease in retrieval of blocks that
      was reversed under subsequent ad lib conditions. This result was confirmed in
      Experiment 4, which also demonstrated concommitant changes in gnawing and object
      retrieval as well as effects on component responses of the retrieval sequence. In
      Experiment 5, continuous exposure to blocks sufficient to reduce gnawing to a low
      level led to a decline in retrieval of these objects that was not reversed by
      discontinuing exposure. These results are consistent with the incentive
      motivational account of retrieval preferences developed in earlier work, and some
      inferences are made about the kinds of processes that could mediate the effects
      of deprivation and habituation. 

PMID- 24895982
TI  - Homing in humans: A different look.
AB  - A current model holds that the long-distance homing abilities of free-ranging
      mammals rest primarily on a strategy of course reversal, based on outward journey
      information. In this study, I measured the ability to orient toward home in
      humans displaced under conditions that promote the use of this strategy, namely
      along an outward route that was direct, and the main bearing of which could be
      extrapolated by reference to a pre-existant mental map and by visual backup
      during the outward journey. Even though the individual course estimates obtained
      did show a certain amount of dispersion and/or error, they were more accurate and
      less dispersed than in experiments by other authors, where subjects could not use
      this strategy, because they were displaced blindfolded and/or along circuitous
      routes. 

PMID- 24895983
TI  - Factors affecting the social ability in pre-school children: An exploratory
      study.
AB  - In a previous paper (Braza et al., 1993) we quantified the social ability of pre
      school children by means of two Indices: Amplitude of Behaviour (I.A.B.) and
      Amplitude of Partnership (I.A.P.). The aim of this study is to explore their
      possible relations with some agents of socialisation and to validate these
      indices of amplitude as a measure of social ability. The variables considered
      (biometrical measurements, family characteristics, and social behaviours in peer
      groups) were ordered by means of a prior analysis of the principal components,
      and the factor scores of each individual in these analyses were chosen as new
      variables. Twenty-six pre-school children attending a nursery in Cadiz (SW Spain)
      were filmed at school during their free-play period. Our results confirm the
      fitness of the Index of Amplitude of Behaviour (I.A.B.) not only as a useful tool
      for the study of socialisation, but also as a possible predictor of later success
      and social adjustment. 

PMID- 24895985
TI  - Prevalent hypovitaminosis D in Crohn's disease correlates highly with mediators
      of osteoimmunology.
AB  - PURPOSE: In the context of osteoimmunology in Crohn's disease, an association was
      hypothesized among vitamin D and members of the TNF-alpha family, known as the
      RANK (receptor-activator of nuclear factor- kappaB)-RANK ligand-osteoprotegerin
      pathway. METHODS: This was a cross-sectional study of 95 patients with Crohn's
      disease (80 with long-standing disease and 15 newly diagnosed, never treated) and
      two control groups (healthy volunteers, n=30; and ulcerative colitis patients,
      n=30). Spine and hip bone mineral density was measured by dual-energy x-ray
      absorptiometry. Serum 25-hydroxyvitamin-D3, TNF-alpha, IL-6, sRANKL,
      osteoprotegerin levels and biochemical markers of bone turnover were analyzed.
      RESULTS: The precursor metabolite, 25(OH)D3, was measured in 95 young adult CD
      patients (47 men, 48 women; median age 30 years). A suboptimal 25(OH)D3 level was
      observed in 90% of CD patients, of whom 40% had a serious deficiency. There was
      no significant difference in 25(OH)D3 levels between CD patients and those with
      ulcerative colitis. Analysis revealed an association between 25(OH)D3 deficiency
      and the increased biogenesis of osteoclastically-active sRANKL (p=0.014) and the
      proinflammatory cytokines TNF-alpha (p=0.015) and IL-6 (p=0.029) . CD patients
      with low bone mineral density had a mean 25(OH)D3 (35+/-18 nmol/l) in the range
      of serious deficiency to insufficiency, whereas mean 25(OH)D3 was higher (49+/-28
      nmol/l) in patients with healthy bone status, although levels were still
      inadequate (p=0.004). The logistic model reported low levels of 25(OH)D3 to be a
      significant predictor of bone disease [odds ratio=2.66(6.8), p < 0.009]. In the
      multivariable analysis, adjusted for several confounding factors, 25(OH)D3,
      sRANKL, IL-6 and TNF-alpha were independently associated with a likelihood of
      bone disease [odds ratio (range): 1.02(2.75); 1.09(3.71); 1.27(6.95)
      respectively, p=0.001]. CONCLUSION: The presented findings suggest that a
      25(OH)D3 deficiency accompanying an inflammatory state in CD is a high risk
      condition for metabolic bone disease.

PMID- 24895986
TI  - How to succeed in research during medical training: a qualitative study.
AB  - PURPOSE: The objective of this study was to examine the characteristics of the
      medical trainee (resident), the supervisor and the project that contribute to
      successful completion of resident-led research and publication in a peer-reviewed
      scientific journal. METHODS: Qualitative, interview-based study of Internal
      Medicine trainees and their supervisors. All interviewed trainees published at
      least one first-author research paper based on a project they completed during
      residency. Thematic analysis was used to explore key themes from interview
      transcripts. An iterative, team-based approach was used to develop a coding
      framework, which was then applied to the data and summarized. Six investigators
      independently reviewed and coded transcripts, discussed the data collectively and
      developed key themes by consensus. RESULTS: Thirty participants (15 residents and
      15 supervisors) were interviewed. Three major themes for successful resident
      research projects emerged: 1) the resident is the project champion; 2)
      supervisors ensure feasibility and timeliness of the project; and, 3) limited
      time is a challenge that can be overcome. Residents were motivated by fellowship
      aspirations, prioritized the project and were genuinely interested in the content
      area. Supervisors were responsible for setting deadlines, limiting the scope of
      the project and ensuring feasibility of the study design. Existing research funds
      and infrastructure from other projects were frequently used by supervisors to
      support research done by trainees. CONCLUSIONS: Successful resident-led research
      projects require leadership and motivation by the resident and engagement,
      reality-checking and deadline-setting by the supervisor. Responsibilities and
      expectations in the resident-supervisor relationship should be set early and
      adequate program resources and funding are required.

PMID- 24895987
TI  - Low-dose ketamine pretreatment reduces oxidative damage and inflammatory response
      following CO2 pneumoperitoneum in rats.
AB  - PURPOSE: The duration of pneumoperitoneum during laparoscopic procedures may
      contribute to post-surgical oxidative stress. Previous studies have shown that
      low-dose ketamine, an anesthetic with anti-inflammatory properties, protects
      various organs from ischemia-reperfusion injury. This study investigated the
      effects of low-dose ketamine on the overproduction of oxidants and the tissue
      damage caused by intra-abdominal pressure during CO2 pneumoperitoneum. METHODS:
      Male Sprague Dawley rats received a CO2 pneumoperitoneum of 15 mmHg and preceded
      by either low-dose ketamine (KP1, 5 mg/kg; KP2, 10 mg/kg) or 0.9% saline (PR, 3
      ml). General anethesia was provided by pentobarbital and sevoflurane. The control
      group (CR) received an intraperitoneal saline injection and sham surgery. Three
      hours after pneumoperitoneum, serum concentrations of interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), superoxide dismutase
      (SOD) and intestinal fatty acid binding protein (iFABP) were measured and liver,
      kidney, lung, and intestine were evaluated for tissue damage. RESULTS: The
      highest plasma MDA, TNF-alpha, IL-6 and iFABP values were observed at T1 (after 3
      hours of pneumoperitoneum) in the PR group, followed by the KP1, KP2, and CR
      groups (P < 0.01). SOD concentrations showed an opposite trend and were highest
      in the CR group, followed by the KP2, KP1, and PR groups (P < 0.01). TNF-alpha
      concentration was significantly lower in the KP2 than the KP1 group (P < 0.05).
      Histopathologic scoring of organ sections demonstrated the lowest scores in the
      KP2 group, followed by the KP1 and PR groups, in an increasing order (P < 0.05).
      CONCLUSION: Pretreatment with low-dose ketamine before general anaesthesia
      protects against potential oxidative damage and inflammatory response caused by
      CO2 pneumoperitoneum.

PMID- 24895988
TI  - MicroRNA-222 promotes the proliferation and migration of cervical cancer cells.
AB  - PURPOSE: This study aimed to investigate the role of small non-coding RNA-222
      (microRNA-222; miR-222) in the development of cervical cancer (CC). METHODS:
      Normal and CC specimens were obtained from 18 patients. HeLa and SiHa cells were
      grown in Dulbecco's modified Eagle's medium. RT-PCR, Western blot, migration
      assay, flow cytometry and immunofluorescence microscopy were used for analyses.
      RESULTS: When compared with normal cervical tissues, miR-222 was upregulated in
      human CC, and the extent of up-regulation was associated with the extent and
      depth of CC invasion. Expression of miR-222 was inversely related to the
      expression of phosphatase and tensin homolog (PTEN) and p27. The reduced the
      expression of PTEN and p27 by miR-222 in HeLa cells and SiHa cells was associated
      with increased proliferation and migration of CC cells. The expression of
      proteins (E-cadherin and paxillin) related to the proliferation and migration was
      also elevated. CONCLUSION: MiR-222 plays an important role in the tumorigenesis
      of CC, possibly by specifically down-regulating p27Kip1 and PTEN. Our findings
      suggest that miR-222 may serve as a new therapeutic target in CC.

PMID- 24895990
TI  - Sex/gender disparities in randomized controlled trials of statins: the impact of
      awareness efforts.
AB  - PURPOSE: Studies have demonstrated gender differences in the burden of
      cardiovascular outcomes for patients with dyslipidemia. Progress in
      identification of the sex/gender composition in Randomized Controlled Trials
      (RCTs) is crucial for understanding the distribution of therapeutics
      effectiveness in the population according to sex/gender. The purpose of this
      study was to investigate the evolving pattern of sex/gender disparity in
      participants of RCTs on statins between 1990 and 2010. A secondary objective was
      to evaluate changes in the pattern of the average age of participants of RCTs on
      statins between 1990 and 2010. METHODS: This review focused on RCTs on statins
      that reported participants' numbers by sex/gender. Studies were identified from
      an initial PubMed search using several combinations of MeSH terms. The search was
      limited to the RCTs on adults in English-language publications. The dates for
      search were set between January 1, 1990 and December 31, 2010. RESULTS: In the
      1990s, RCTs on statins with an average of more than 500 participants included
      18.6% women [95% Confidence Interval (95% C.I.): 16.31%, 21.13%]. By the first
      decade of the 2000s, women comprised, on average, 31.45% [29.45%, 32.52% (95%
      C.I.)] of the total cohort of RCTs with more than 500 participants. Regression
      analysis illustrated a significant increase in the recruitment of women for RCTs
      of statins (p-value < 0.01). Furthermore, analysis of the average age of
      participants illustrated a significant trend (p-value = 0.03) towards an increase
      in the average age of the participants in RCTs on statin between 1990 and 2010:
      the average age of participants in the 1990s was 58 years [56, 60 (95% C.I.)] and
      in the 2000s it was 62 years [56, 60 (95% C.I.)]. CONCLUSION: This study
      demonstrates significant progress in the inclusion of women in RCTs on statins.
      This finding reflects the efforts of different agencies and groups to increase
      the representation of women in clinical trials.

PMID- 24895989
TI  - Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat
      model of unilateral ureteral obstruction.
AB  - PURPOSE: The purpose of this study was to explore effects of rapamycin on renal
      hypoxia, interstitial inflammation and fibrosis, and the expression of
      transforming growth factor beta1 (TGF-beta1), vascular endothelial growth factor
      (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO).
      METHODS: Male Sprague-Dawley rats (n=36) were randomly divided into three groups
      (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum
      creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and
      24-h urine protein levels were measured. The extent of interstitial fibrosis was
      determined by Masson's trichrome staining. ED-1 positive macrophages, type III
      collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions
      were detected using immunohistochemical staining, real-time PCR and Western blot.
      RESULTS: UUO induced an elevation in Scr, renal hypoxia, inflammation,
      interstitial fibrosis, TGF-beta1, VEGF, Flk-1, and Flt-1 mRNA and protein
      expression levels (P < 0.05). Rapamycin alleviated the UUO-induced renal hypoxia,
      infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and
      7). Rapamycin also down-regulated the UUO-induced elevated expression levels of
      TGF-beta1 and Flt-1 mRNA and protein (P < 0.05). Rapamycin decreased VEGF mRNA
      and protein expression at day 3, and increased Flk-1 mRNA and protein expression
      at day 7, compared with the UUO group (P < 0.05). CONCLUSION: Rapamycin shows
      beneficial effects by reducing UUO-induced renal hypoxia, inflammation and
      tubulointerstitial fibrosis.

PMID- 24895991
TI  - Dipeptidyl peptidase-4 inhibition improves left ventricular function in chronic
      kidney disease.
AB  - PURPOSE: Heart failure with preserved ejection fraction (HFpEF) is a common
      comorbidity in people with chronic kidney disease (CKD) for which no evidence
      based treatment currently exists. Recently, a group of anti-hyperglycemic agents
      used in the treatment of Type 2 diabetes, termed incretin-based therapies, have
      come under scrutiny for their putative glucose-independent effects on cardiac
      function. In the present study, the actions of the dipeptidyl peptidase-4 (DPP-4)
      inhibitor class of incretin-based therapy in preventing HFpEF induced by chronic
      renal impairment were investigated. METHODS: Sham-operated and subtotally
      nephrectomized rats were randomized to receive the DPP-4 inhibitors, linagliptin
      or sitagliptin for seven weeks before assessment of cardiac and renal structure
      and function. RESULTS: Analysis of pressure-volume loops revealed that both
      linagliptin and sitagliptin prevented the development of cardiac diastolic
      dysfunction, with cardiac collagen I synthesis also being reduced by DPP-4
      inhibition. These attenuating cardiac effects occurred without change in renal
      function or structure where, in the doses administered, neither linagliptin nor
      sitagliptin affected GFR decline, proteinuria, renal fibrosis or the increased
      urinary excretion of biomarkers of renal toxicity. CONCLUSION: The beneficial
      cardiac effects of DPP-4 inhibition, in the absence of a concurrent improvement
      in renal dysfunction, raise the possibility that these agents may confer
      cardiovascular advantages in the CKD population.

PMID- 24895992
TI  - Visceral fat reflects disease activity in patients with ankylosing spondylitis.
AB  - PURPOSE: Response to infliximab treatment diminishes as body mass index (BMI)
      increases in patients with ankylosing spondylitis (AS). The purpose of the study
      was to determine if diminished response to infliximab treatment in patients with
      AS could be associated with increased visceral adipose tissue rather than
      increased BMI. METHODS: Twenty six AS patients (21 males and five females) who
      fulfilled the modified New York criteria and who were currently receiving
      infliximab treatment were enrolled in the study. Pain was measured by the visual
      analogue scale (VAS). The disease activity and functional status were assessed by
      the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index
      (BASFI). The Bath AS Metrology Index (BASMI) was used to evaluate mobility
      restrictions. Weight and visceral body composition were measured without shoes in
      light indoor clothes using a bio-impedance meter. RESULTS: There was a
      significant correlation between visceral adipose tissue amount and disease
      activity under infliximab treatment. In correlation analysis, visceral fat showed
      significant correlations between BASDAI (r=0.545, p=0.004) and VAS (r=0.458,
      p=0.019). Total body fat also showed a significant correlation with BASDAI
      (r=0.463, p=0.017). CONCLUSION: A significant correlation was found between
      visceral adipose tissue amount and disease activity in patients with AS.

PMID- 24895993
TI  - Antioxidants from Gerbera piloselloides: an ethnomedicinal plant from
      southwestern China.
AB  - Gerbera piloselloides is a very important ethnobotanical and ethnomedicinal plant
      used by indigenous peoples in southwestern China. Ten compounds were obtained
      using activity-guided isolation, including a parasorbosid derivative, two caffeic
      acid derivatives, two coumarins and five flavonoids, and identified from the
      whole plant of G. piloselloides. This is the first report of compound 5 as
      natural product. Six compounds were reported in the Gerbera genus for the first
      time. The antioxidant activity of all the compounds was evaluated by using ABTS
      assay, and the chemotaxonomic implication of this study was also discussed. 

PMID- 24895994
TI  - Gene therapy in patient-specific stem cell lines and a preclinical model of
      retinitis pigmentosa with membrane frizzled-related protein defects.
AB  - Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive
      retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)
      specific membrane receptor of unknown function. In patient-specific induced
      pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its
      dicistronic partner CTRP5, are critical to the regulation of actin organization.
      Overexpression of CTRP5 in naive human RPE cells phenocopied behavior of MFRP
      deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP
      rescued the actin disorganization phenotype and restored apical microvilli in
      patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE
      recovered pigmentation and transepithelial resistance. The efficacy of AAV
      mediated gene therapy was also evaluated in Mfrp(rd6)/Mfrp(rd6) mice--an
      established preclinical model of RP--and long-term improvement in visual function
      was observed in AAV-Mfrp-treated mice. This report is the first to indicate the
      successful use of human iPS-RPE cells as a recipient for gene therapy. The
      observed favorable response to gene therapy in both patient-specific cell lines,
      and the Mfrp(rd6)/Mfrp(rd6) preclinical model suggests that this form of
      degeneration caused by MFRP mutations is a potential target for interventional
      trials.

PMID- 24895995
TI  - Role of cysteine-rich 61 protein (CCN1) in macrophage-mediated oncolytic herpes
      simplex virus clearance.
AB  - Glioblastoma is a devastating disease, and there is an urgent need to develop
      novel therapies, such as oncolytic HSV1 (OV) to effectively target tumor cells.
      OV therapy depends on tumor-specific replication leading to destruction of
      neoplastic tissues. Host responses that curtail virus replication limit its
      efficacy in vivo. We have previously shown that cysteine-rich 61 protein (CCN1)
      activates a type 1 IFN antiviral defense response in glioblastoma cells.
      Incorporating TCGA data, we found CCN1 expression to be a negative prognostic
      factor for glioblastoma patients. Based on this, we used neutralizing antibodies
      against CCN1 to investigate its effect on OV therapy. Use of an anti-CCN1
      antibody in mice bearing glioblastomas treated with OV led to enhanced virus
      expression along with reduced immune cell infiltration. OV-induced CCN1 increases
      macrophage migration toward infected glioblastoma cells by directly binding
      macrophages and also by enhancing the proinflammatory activation of macrophages
      inducing MCP-1 expression in glioblastoma cells. Activation of macrophages by
      CCN1 also increases viral clearance. Neutralization of integrin alphaMbeta2
      reversed CCN1-induced macrophage activation and migration, and reduced MCP-1
      expression by glioblastoma cells. Our findings reveal that CCN1 plays a novel
      role in pathogen clearance; increasing macrophage infiltration and activation
      resulting in increased virus clearance in tumors. 

PMID- 24895996
TI  - miR-148a- and miR-216a-regulated oncolytic adenoviruses targeting pancreatic
      tumors attenuate tissue damage without perturbation of miRNA activity.
AB  - Oncolytic virotherapy shows promise for pancreatic ductal adenocarcinoma (PDAC)
      treatment, but there is the need to minimize associated-toxicities. In the
      current work, we engineered artificial target sites recognized by miR-216a and/or
      miR-148a to provide pancreatic tumor-selectivity to replication-competent
      adenoviruses (Ad-miRTs) and improve their safety profile. Expression analysis in
      PDAC patients identified miR-148a and miR-216a downregulated in resectable
      (FC(miR-148a) = 0.044, P < 0.05; FC(miR-216a) = 0.017, P < 0.05), locally
      advanced (FC(miR-148a) = 0.038, P < 0.001; FC(miR-216a) = 0.001, P < 0.001) and
      metastatic tumors (FC(miR-148a) = 0.041, P < 0.01; FC(miR-216a) = 0.002, P <
      0.001). In mouse tissues, miR-216a was highly specific of the exocrine pancreas
      whereas miR-148a was abundant in the exocrine pancreas, Langerhans islets, and
      the liver. In line with the miRNA content and the miRNA target site design, we
      show E1A gene expression and viral propagation efficiently controlled in Ad-miRT
      infected cells. Consequently, Ad-miRT-infected mice presented reduced pancreatic
      and liver damage without perturbation of the endogenous miRNAs and their targets.
      Interestingly, the 8-miR148aT design showed repressing activity by all miR
      148/152 family members with significant detargeting effects in the pancreas and
      liver. Ad-miRTs preserved their oncolytic activity and triggered strong
      antitumoral responses. This study provides preclinical evidences of miR-148a and
      miR-216a target site insertions to confer adenoviral selectivity and proposes 8
      miR148aT as an optimal detargeting strategy for genetically-engineered therapies
      against PDAC.

PMID- 24895999
TI  - The olfaction in Proteus anguinus: a behavioural and cytological study.
AB  - Life and development in complete darkness for a strictly cavernicolous Urodele
      species such as Proteus raises the problem of orientation and environmental
      perception. An experimental study of olfaction in Proteus anguinus was undertaken
      on two complementary aspects: (a) a anatomical and ultrastructural aspect (photon
      and electron microscopy); and (b) a behavioural aspect, by testing Proteus'
      sensitivity to decreasing amounts of dead prey (chironomid larvae) in a choice
      chamber. The results show that: (a) Proteus' olfactory epithelium clearly
      belonged to the general model established for all vertebrates, with a pseudo
      stratified structure mainly composed of the three classical cell types (sensory
      cells, supporting cells and basal cells). With the unusual thickness of the
      epithelium common to the Proteidae, a fourth cell type is observed in Proteus;
      and (b) Proteus shows a well-developed olfactive sense: the sensitivity threshold
      occurs around 1 g of prey (in a 250 cm(3)/min water current). This relatively low
      detection threshold implies the use of an outstanding sense of smell probably due
      to the particular necessities of the subterranean environment. The experiments
      also emphasize the effects of environmental factors on Proteus' response to
      experiments, and the role of thigmotactism. 

PMID- 24896000
TI  - Home ranges and satellite tactics of male green swordtails (Xiphophorus helleri)
      in nature.
AB  - Dominance relationships were studied between marked or otherwise individually
      recognizable male green swordtails in a creek at Lake Catemaco and in a tributary
      of the Rio Atoyac (Veracruz, Mexico). The Atoyac population is unique because of
      a high degree of polymorphism, including both macromelanophore spotting and a
      micromelanophore tailspot pattern. During the dry season males living in the same
      area maintained a linear social hierarchy for periods of many days. The
      subordinate males settled down either in the same home ranges or in home ranges
      largely overlapping with that of dominant males. Although dominant males
      untiringly chased the subordinate males away, they returned persistently and
      achieved the status of non-tolerated satellites. Females were less stationary and
      presumably passed through many male home ranges during their feeding activities.
      The data clearly demonstrate that green swordtails live in complex social systems
      in which male-male competition and probably also female mate choice are likely to
      be essential factors for individual reproductive success. 

PMID- 24895998
TI  - Lentiviral arrays for live-cell dynamic monitoring of gene and pathway activity
      during stem cell differentiation.
AB  - Uncovering the complexity of mesenchymal stem cell (MSC) differentiation requires
      novel methods to capture the dynamics of the process in a quantitative and high
      throughput manner. To this end, we developed a lentiviral array (LVA) of
      reporters to capture the dynamics of gene and pathway activity during MSC
      differentiation into adipogenic, chondrogenic, and osteogenic lineages. Our
      results identified signature promoters and pathways with unique activation
      profile for each MSC lineage. In combination with chemical inhibitors, lineage
      specific reporters predicted the effects of signaling pathway perturbations on
      MSC differentiation. Interestingly, some pathways were critical for
      differentiation into all lineages, while others had differential effects on each
      lineage. Our study suggests that when combined with large chemical or siRNA
      libraries, the reporter LVA can be used to uncover novel genes and signaling
      pathways affecting complex biological processes such as stem cell differentiation
      or reprogramming. 

PMID- 24896001
TI  - A sociogram for the cranes of the world.
AB  - The behavioral repertoire for the world's 15 species of cranes includes over 100
      behavioral acts with clear social significance. Each species performs at least 60
      discrete social postures, vocalizations, displays, and activities. Because all
      but a handful of the stereotyped social displays are common to all species, the
      presence or absence of social displays was useful only to a limited degree in
      comparing the relatedness of established crane taxonomic groups. However, the
      breadth of the repertoire for each species and for the family Gruidae tentatively
      places cranes at the apex of social complexity (at least for stereotyped
      displays) in the animal world. 

PMID- 24895997
TI  - Cytotoxic and regulatory properties of circulating Vdelta1+ gammadelta T cells: a
      new player on the cell therapy field?
AB  - Exploration of cancer immunotherapy strategies that incorporate gammadelta T
      cells as primary mediators of antitumor immunity are just beginning to be
      explored and with a primary focus on the use of manufactured phosphoantigen
      stimulated Vgamma9Vdelta2 T cells. Increasing evidence, however, supports a
      critical role for Vdelta1+ gammadelta T cells, a minor subset in peripheral blood
      with distinct innate recognition properties that possess powerful tumoricidal
      activity. They are activated by a host of ligands including stress-induced self
      antigens, glycolipids presented by CD1c/d, and potentially many others that
      currently remain unidentified. In contrast to Vgamma9Vdelta2 T cells, tumor
      reactive Vdelta1+ T cells are not as susceptible to activation-induced cell death
      and can persist in the circulation for many years, potentially offering durable
      immunity to some cancers. In addition, specific populations of Vdelta1+ T cells
      can also exhibit immunosuppressive and regulatory properties, a function that can
      also be exploited for therapeutic purposes. This review explores the biology,
      function, manufacturing strategies, and potential therapeutic role of Vdelta1+ T
      cells. We also discuss clinical experience with Vdelta1+ T cells in the setting
      of cancer, as well as the potential of and barriers to the development of
      Vdelta1+ T cell-based adoptive cell therapy strategies. 

PMID- 24896002
TI  - The effects of stopping and restarting a session on within-session patterns of
      responding.
AB  - Rats pressed levers for sweetened condensed milk reinforcers delivered according
      to a multiple variable-interval 1-min, variable-interval 1-min schedule during 60
      min baseline sessions. The obtained pattern of responding was an early-session
      increase in responding followed by a relatively constant rate of responding
      during the remainder of the session. In the experimental conditions of experiment
      1, sessions were interrupted by a blackout or timeout lasting either 5, 10, or 30
      min. Responding following 5- or 10-min interruptions resembled the constant rate
      of responding late in the baseline sessions. However, responding increased before
      30-min interruptions and increased again after the interruption. This change in
      the pattern of responding was best described as a 'restarting' of the within
      session pattern of responding. In experiment 2, a 30-min blackout interrupted
      sessions. However, reinforcers were presented intermittently during the blackout.
      Responding did not restart following the 30-min blackout-with-reinforcers
      condition. These results suggest that the mere presentation of reinforcers is
      sufficient to maintain within-session changes in responding. 

PMID- 24896003
TI  - Place preferences of Japanese quail given a permanent choice between a social or
      a non-social but enriched situation.
AB  - Japanese quail from two lines selected for high (HSR) or low (LSR) levels of
      social reinstatement behaviour were permanently placed from 2 days to 6 weeks of
      age in a situation where one tested animal had the choice between being in social
      contact with a stimulus animal in a bare compartment of the cage or out of visual
      contact with the stimulus animal in a relatively rich environment containing
      food, water and wood shavings. The young (1 or 2 weeks of age) quails spent most
      of their time (over 80%) in the social compartment, about 10% feeding and
      drinking, and about 10% performing other activities in the non-social
      compartment. Hardly any differences appeared between the two lines when 1 or 2
      weeks old, but at 4 weeks of age the LSR quails started to decrease the time
      spent in the social compartment and this phenomenon only appeared at 6 weeks of
      age and to a lesser extent in the HSR quails. At 4 and 6 weeks the differences
      between lines were significant. The lack of difference between the two lines in
      young quails can be explained by the very high social motivation expressed even
      by LSR quails in the conditions of the study. When they are older line
      differences are expressed. This change coincides with the time when the natural
      coveys start to disperse and also with the beginning of sexual development. These
      results confirm the hypothesis of Francois et al. (Francois, N., Mills, A.D.,
      Faure, J.M., 1997. Inter-individual distances in Japanese quail (Coturnix
      japonica) selected for high or low levels of sociability. Behav. Process. (in
      press)) that line differences in social motivation persist into adult or near
      adult life and can still be demonstrated, provided the circumstances are such
      that aggression does not prevent close social contact. 

PMID- 24896004
TI  - Methodological aspects of the interval trapping method with comments on nocturnal
      activity patterns in house mice living in outdoor enclosures.
AB  - Activity periods in small rodents are influenced by a variety of factors
      including climatic conditions, photoperiod, resource availability, and
      competitors. The timing of nocturnal activity was examined in free-living house
      mice inhabiting large outdoor enclosures. Live-traps were checked at 2-h
      intervals on specified nights. Mice were more active just after dusk and less
      active just before dawn. There was no significant differential timing of activity
      by age or sex. Dominant males were more active in the latter half of the night
      and subordinate males were more active in the first half of the night. Questions
      pertaining to the availability of traps, the proportion of mice still not
      captured, density effects on capture rates, and human activity influencing mouse
      activity were also tested. On average, more than 86% of the traps remained open
      even for the 2-h interval nearest dawn. A minimum of 70% of the trappable mice
      were not captured on a given trap night. The rate of mouse captures did not
      increase with increasing density. There was no difference in the overall mean
      number of mice caught on nights with and without interval trapping. However,
      capture rates were significantly lower in the period after a 2-h trapping
      interval than in the periods before or during that interval. Adult males and
      adult non-reproductive females were caught again sooner if they spent more time
      in the trap. There was no effect of the amount of time spent in the trap on the
      time to recapture for adult reproductive females or male or female juveniles. 

PMID- 24896005
TI  - Is food recognition in an unfamiliar environment a long-term effect of stimulus
      or local enhancement? A study in the juvenile canary.
AB  - The processes involved in the social transmission of recognition and consumption
      of hemp seeds were investigated in juvenile canaries (Serinus canarius). The
      combined influences of observation of a parent feeding, presence of parent and
      accessibility of seeds on future seed consumption were investigated in six
      experimental conditions (each employing 15 individuals). We found that: (i) local
      enhancement and social facilitation were not required for social transmission,
      (ii) transmission took place if the juvenile observed seeds in the vicinity of
      the parent, whether the seeds were accessible or not (mere presence effect).
      Accessibility, however, did favour transmission; (iii) observation of a parent
      feeding was sufficient for social transmission of information even if the seeds
      were not available during interactions with the adult. The juvenile thus appeared
      to recognise seeds by stimulus enhancement, and this recognition was maintained
      in both space and time. The various interactions with adults enabled the
      juveniles to identify edible objects even in an unfamiliar environment. 

PMID- 24896006
TI  - Changing rearing environments and problem solving flexibility in rats.
AB  - Rats were reared from weaning onwards in impoverished (IC), social (SC) or
      enriched (EC) environments. In addition, some groups were moved from an enriched
      to an impoverished environment, or vice versa, either once or three times during
      rearing. After 2 months of differential rearing, animals were tested in a
      multidimensional discrimination procedure in an operant chamber, where
      reinforcements were given on a random schedule, that is, uncorrelated with the
      choices made by the animals. It was found that eventually all rats took up
      alternating place. However, enriched subjects did so more consistently than
      impoverished or socially reared subjects. Animals shifted three times, behaved
      more routine-like than did animals never changed or changed only once; such
      animals did so to a greater degree than did the enriched animals. In comparison,
      impoverished animals, and those never changed or changed once, more often kept
      responding to the environmental cues. The results are discussed in relation to
      general interpretations of the effects of impoverishment and enrichment in terms
      of behavioural flexibility, over-attention, and in relation to styles of coping.
      It is argued that, contrary to welfare people's claims, the behavioural
      differences found are well within the range of normal individual variation. 

PMID- 24896007
TI  - Reinforcing property of music in Java sparrows (Padda oryzivora).
AB  - The reinforcing property of music for Java sparrows was examined in a chamber
      with three perches. One of the end perches produced music by Bach while the other
      perch produced music by Schoenberg. Two of four birds significantly stayed longer
      on the perch associated with Bach music and retained their preference of Bach to
      Schoenberg when other pieces of music by Bach and Schoenberg were used. These two
      birds also preferred Vivaldi to Carter, suggesting preference for classical music
      over modern music. One of the two birds that did not show a preference between
      Bach and Schoenberg preferred Bach to a white noise, but the remaining one did
      not show any musical preference to noise. These results suggest that Java
      sparrows have musical preference and that the reinforcing properties depend on
      individuals. 

PMID- 24896008
TI  - External factors and causation of dustbathing in domestic hens.
AB  - Dustbathing is known to be motivated by complex interactions between internal
      factors which build up over time and external factors, such as the sight of a
      dusty substrate. In this study, the effects of other external factors were
      investigated. Environmental temperature was shown to be important; frequencies of
      dustbathing were greater when hens were held at 22 than at 10 degrees C (P<0.01).
      In a second experiment, a radiant heat source or a radiant heat+light source,
      balanced to give the same radiant heat, resulted in more dustbathing behaviour
      during a 1-h stimulus period than during the same period with no stimulus
      (P<0.05). Components of dustbathing were increased more by the heat+light
      stimulus than by the heat stimulus alone (P<0.03). In a third experiment, the
      amount of dustbathing performed by individual hens in cages with dustbaths was
      increased by the presence of a group of hens dustbathing in an adjoining pen with
      a dustbath compared with the amount occurring when the hens were absent from the
      pen. 

PMID- 24896009
TI  - Female bank vole (Clethrionomys glareolus) recognition: preference for the stud
      male.
AB  - Pregnant and nursing bank vole (Clethrionomys glareolus) females were
      investigated for their ability to recognize their mated male on the basis of
      chemical cues. In a two-choice test pregnant females showed a strong preference,
      manifested by higher frequency of sniffs and time spent sniffing, to the odour of
      a stud male over that of unfamiliar male, but only during the days after
      insemination and around implantation. As gestation proceeds females exhibited no
      affinity for either of these two kinds of males. Olfactory bulbectomy abolished a
      pregnant females preference for her stud male. A lactating female chose the odour
      of her sexual partner untill the time of weaning of her young. Separation of the
      female from her pups during the early post partum period shortens the time of
      memory for the scent of the stud male. The results indicate that bank vole
      females form olfactory memory to the odour of stud males and its duration depends
      on physiological state of the females. 

PMID- 24896010
TI  - Poor complementary feeding practices and high anaemia prevalence among infants
      and young children in rural central and western China.
AB  - BACKGROUND/OBJECTIVES: Infant and young child feeding (IYCF) has not been
      documented in central and western China, where anaemia is prevalent. To support
      policy advocacy, we assessed IYCF and anaemia there using standardized methods.
      SUBJECTS/METHODS: A community-based, cross-sectional survey of 2244 children aged
      6-23 months in 26 counties of 12 provinces. Analysis of associations between
      haemoglobin concentration (HC), IYCF indicators and other variables using crude
      and multivariate techniques. RESULTS: Only 41.6% of those surveyed consumed a
      minimum acceptable diet. Fewer still-breastfeeding than non-breastfeeding
      children consumed the recommended minimum dietary diversity (51.7 versus 71.9%;
      P<0.001), meal frequency (57.7% v. 81.5%; P<0.001) or iron-rich food (63.3% v.
      78.9%; P<0.001). Anaemia (51.3% overall) fell with age but was significantly
      associated with male sex, extreme poverty, minority ethnicity, breastfeeding and
      higher altitude. Dietary diversity, iron intake, growth monitoring and being left
      behind by out-migrating parents were protective against anaemia. A structural
      equation model demonstrated associations between IYCF, HC and other variables.
      Meal frequency, iron intake and altitude were directly and positively associated
      with HC; dietary diversity was indirectly associated. Health service uptake was
      not associated. Continued breastfeeding was directly associated with poor IYCF
      and indirectly with reduced HC, as were having a sibling and poor maternal
      education. CONCLUSION: Infant and young child anaemia is highly prevalent and
      IYCF is poor in rural central and western China. Continued breastfeeding and
      certain other variables indicate risk of poor IYCF and anaemia. Major policy
      commitment to reducing iron deficiency and improving IYCF is needed for China's
      rural poor.

PMID- 24896011
TI  - Diet quality and diet costs in German children and adolescents.
AB  - We examined the association between diet costs and diet quality in a sample of
      children and adolescents using data from the ongoing longitudinal (open cohort)
      DONALD (Dortmund Nutritional and Anthropometric Longitudinally Designed) study.
      Children and adolescents aged 4-18 years (255 boys and 239 girls) provided 1100
      yearly collected 3-day weighted dietary records. Linear mixed (effects) models
      were used to analyze the association between diet costs ([euro ;[sol;day,
      estimated using retail food prices) and the Nutrient Quality Index (NQI) and the
      Healthy Nutrition Score for Kids and Youth (HuSKY). Analysis were stratified for
      low-quality records (score<median) and high-quality records (score>median). No
      significant association was found in the low-quality records, whereas in the high
      quality records the association was significantly positive for both scores (HuSKY
      P=0.016, NQI P<0.0001). In conclusion, a substantial part of our sample could
      increase their diet quality without a noteworthy increase of expenditure.

PMID- 24896012
TI  - Knowledge of appropriate foods and beverages needed for weight loss and diet of
      patients in an Obesity Clinic.
AB  - BACKGROUND/OBJECTIVE: Knowledge does not automatically translate into behaviour
      change. This study examined the relationship between knowledge of appropriate
      foods and beverages needed for weight loss and the diet of patients seeking
      weight management. SUBJECTS/METHODS: A cross-sectional study of 104 consecutive
      first-time patients (55 women and 49 men) seeking weight management, with a mean
      age of 37.3 +/- 11.8 years and a BMI of 44.9 +/- 9.4 kg/m(2), was carried out;
      67.3% of these patients had a BMI of 40 kg/m(2) or greater. Patients were told to
      design a detailed weight-loss diet that they would recommend to a person with the
      same characteristics (recommended diet or RD) as themselves and asked whether the
      RD was similar to their own. Consumed diet (CD) was assessed by a different
      dietitian through a 24-h diet recall. Estimated energy requirement (EER), energy
      content of RD and CD and number of fruit, vegetable, cereal and sweetened
      beverage portions were calculated. Statistical differences were assessed through
      the Pearson's correlation and the Wilcoxon's rank-sum tests. RESULTS: RD and CD
      were 1104 +/- 243 and 1976 +/- 708 kcal for women and 1254 +/- 287 and 2743 +/-
      1244 kcal for men, with statistical differences for both genders (P<0.001).
      Energy content of the RD was lower than the EER in men and women (P<0.001); CD
      was lower than the EER in women (P=0.033). Number of fruit/vegetable portions was
      lower in CD than in the RD in women (P<0.001), whereas cereal and sweetened
      beverage portions were higher in CD than in the RD in both genders (P<0.001). RD
      was not followed by 46.1% of the patients. CONCLUSIONS: Patients with obesity
      seeking care have knowledge of the appropriate dietary strategies needed for
      weight loss, but do not translate it into practice. Treatment approaches should
      include tools that help patients to implement their nutrition knowledge.

PMID- 24896013
TI  - Antimicrobial activity of ceftaroline and other anti-infective agents against
      microbial pathogens recovered from the surgical intensive care patient
      population: a prevalence analysis.
AB  - BACKGROUND: Ceftaroline is a new parenteral cephalosporin agent with excellent
      activity against methicillin-sensitive (MSSA) and resistant strains of
      Staphylococcus aureus (MRSA). Critically ill surgical patients are susceptible to
      infection, often by multi-drug-resistant pathogens. The activity of ceftaroline
      against such pathogens has not been described. METHODS: Three hundred thirty-five
      consecutive microbial isolates were collected from surgical wounds or abscesses,
      respiratory, urine, and blood cultures from patients in the surgical intensive
      care unit (SICU) of a major tertiary medical center. Using Clinical and
      Laboratory Standards Institute (CLSI) standard methodology and published
      breakpoints, all aerobic, facultative anaerobic isolates were tested against
      ceftaroline and selected comparative antimicrobial agents. RESULTS: All
      staphylococcal isolates were susceptible to ceftaroline at a breakpoint of <=1.0
      mcg/mL. In addition, ceftaroline exhibited excellent activity against all
      streptococcal clinical isolates and non-ESBL-producing strains of
      Enterobacteriaceae (93.5%) recovered from SICU patients. Ceftaroline was inactive
      against ESBL-producing Enterobacteriaceae, Pseudomonas aeruginosa, vancomycin
      resistant enterococci, and selective gram-negative anaerobic bacteria.
      CONCLUSIONS: At present, ceftaroline is the only cephalosporin agent that is
      active against community and healthcare-associated MRSA. Further studies are
      needed to validate the benefit of this novel broad-spectrum anti-infective agent
      for the treatment of susceptible serious infections in the SICU patient
      population.

PMID- 24896014
TI  - Retraction: Agarwal et Al. Dynamic action of carotenoids in cardioprotection and
      maintenance of cardiac health, molecules 2012, 17, 4755-4769.

PMID- 24896015
TI  - Introduction.

PMID- 24896016
TI  - Neurogenetic basis of cognition: Facts and hypotheses.
AB  - In the natural setting, cognitive processes direct behavioural adjustments and
      sometimes result in behavioural novelties which allow the organism to cope with
      environmental pressures. The resulting behavioural changes exhibit various forms
      which are dependent upon different causal factors and cognitive processes. Under
      long-lasting environmental changes, these behavioural adaptations can become
      hereditary either through the process of cultural transmission or through genetic
      mechanisms sensitive to selective forces acting on genotypes. In the last few
      years, neuroethology and behavioural neurosciences have produced an increasing
      amount of precise knowledge about brain-behaviour relationships, neurobiological
      bases of cognitive processes and their development. Unfortunately, the approach
      to these phenomena is basically normative and does not tell us much about non
      pathological determinants of individual variation in cognitive and behavioural
      competences. In contrast, the differential approach has provided some cases of
      structural variations in the brain which are under genetic control and thus
      liable to evolve under selective pressures. Brain size, the ratio of various
      brain structures to the total brain, the number and density of neurons in various
      parts of the brain and the variations of neuronal circuitry are potential
      candidates. This paper reviews them and examines their possible behavioural and
      cognitive outcomes. The issue here is to examine if and where in the brain
      potential conditions occur that would allow the genetic evolution of cognitive
      processes. 

PMID- 24896017
TI  - Genetic variability, individuality and the evolution of the mammalian brain.
AB  - The neo-Darwinian theory of evolution has difficulty in explaining the rapid
      evolution of mammalian brain and behavior. I shall argue that the plasticity
      mechanisms of the brain (i.e., system homeostasis, developmental reorganization,
      structural adult plasticity, and cognition and learning) have evolved primarily
      as genetic buffer systems which protect subtle mutations influencing brain
      structures from natural selection. These buffer systems permit accumulation of
      genetic variation in the higher system levels of the brain (simply defined as
      structures with late differentiation), while low-level systems are kept constant
      by natural selection. The organization of this intrinsic genetic buffering system
      provides several features facilitating neo-Darwinian evolution: In conclusion,
      the evolutionary appearance of cognition and intelligence is an ordinary
      biological mechanism compensating evolutionary drags such as long lifespans and
      fewer offspring. The concept has heuristic value for identifying gene-brain
      behavior relationships and for explaining behavioral consequences of artifical
      gene deletions. 

PMID- 24896018
TI  - Evolution and genetic control of mate recognition and stimulation in Drosophila.
AB  - Behavioural, genetic, and evolutionary studies of courtship behaviour, its
      function and its bases are reviewed for the four species of the Drosophila
      melanogaster complex (D. melanogaster, D. simulans, D. mauritiana and D.
      sechellia). The roles of sexual selection and of sensory mechanisms in shaping
      courtship are emphasised, and particular attention is paid to the role of chemo
      sensory factors. 

PMID- 24896019
TI  - Cognitive approach of spatial and temporal information processing in insects.
AB  - Within the theoretical framework of adaptive significance, it is often claimed
      that insects learn just what they are genetically programmed to learn.
      Consequently, because of the alleged lack of plasticity of their behaviour, many
      learning tests applied to insects are limited to very simple associative Stimulus
      Response research paradigms. If the behaviouristic approach can explain most of
      the behavioural responses of insect species facing very simple situations,
      behaviour requires other strategies for learning and memorizing environmental
      information in species confronting complex and variable ecological conditions, as
      it is the case for many hymenoptera species. Among them, forager ants Cataglyphis
      cursor can discriminate, select, store and represent spatial information within a
      few days, allowing them to locate their remote nest in a highly controlled visual
      environment. They can learn something about the spatial arrangement of the
      landmarks configuration and accurately home even in the absence of the main
      visual stimulus associated to this place. Ectatomma ruidum ants are also capable
      to store jointly spatial and temporal information in order to schedule their
      feeding behaviour. Thus, the representational format of spatial and temporal
      memories in some insect species appears to be more subtle than is generally
      assumed when compared to other animal species. 

PMID- 24896020
TI  - Towards a cognitive understanding of odor discrimination: Combining experimental
      and theoretical approaches.
AB  - In response to changes in odorous environmental conditions, most species (ranging
      from lower invertebrates to mammals), demonstrate high adaptive behavioral
      performances. Complex natural chemical signals (i.e. odorous blends involved in
      food search), are particularly unstable and fluctuating, in quality, space and
      time. Nevertheless, adapted behavioral responses related to meaningful odor
      signals can be observed even in complex natural odorous environments,
      demonstrating that the underlying olfactory neural network is a very dynamic
      pattern recognition device. In the honeybee, a large amount of experimental data
      have been collected at different levels of observation within the olfactory
      system, from signal processing to behavior, including cellular and molecular
      properties. However, no set of data considered by itself can give insight into
      the mechanisms underlying odor discrimination and pattern recognition. Here, by
      concentrating on deciphering the neural mechanisms underlying encoding and
      decoding of the olfactory signal in the two first layers of the neural network,
      we illustrate how a theoretical approach helps us to integrate the different
      experimental data and to extract relevant parameters (features) which might be
      selected and used to store an odor representation in a behavioral context. 

PMID- 24896021
TI  - Categorization in birdsong: from behavioural to neuronal responses.
AB  - This paper reviews some aspects on the perceptual processes involved in the
      categorization of natural sounds, especially in birdsong. Different models have
      been proposed to account for the simple filtering observed at the peripheral
      level to the recognition processes, revealed through behavioural responses. Some
      studies have shown that neurons in some of the motor nuclei (high vocal center)
      in the brain are specialized towards precise species-specific characteristics,
      even the bird's own song. These results indicate a high level of integration, but
      little is known about intermediate levels. Studies of the perception of natural
      songs by starlings show that many neurons in field L are selective towards
      particular features of the songs. Neighbouring neurons tend to show complementary
      or similar selectivities, determining areas of response. Such studies emphasize
      the importance of combining ethology and neurophysiology, and of the use of
      natural sounds to test neuronal selectivity. 

PMID- 24896022
TI  - Philopatry in mouflon rams during the rutting season: Psycho-ethological
      determinism and functional consequences.
AB  - Our study of mouflon (Ovis musimon) rams in the Caroux-Espinouse massif (southern
      France) shows that several forms of philopatry occur. Some of the rams were
      sedentary, as were the ewes, up to the age of four years. Most of the rams,
      however, started to enlarge their home range from the age of two years. Rams of
      intermediate age visited their birth ranges during various periods of the year,
      whereas the adult males returned only during the rut. As potential mates were
      present on the home ranges of most of the dispersive males, it is difficult to
      interpret this process merely in terms of adaptation. We propose, instead, a
      psycho-ethological explanation, whereby the physiological disturbances
      intervening during the rut alter the significance of the range, the ram having to
      update the whole set of its sensory-motor past. This interpretation suggests that
      the animal has no representation of any pre-defined place, nor of any fixed aim.
      Rams would be able to reduce the imbalances they experience by creating a type of
      behaviour driven by a self-referential process, where spatial investment would
      outweigh any other evaluation, as an adaptative cost related to a possible
      inbreeding. This approach leads to reconsider the importance of spatial
      investment in animal's cognition and generally speaking the way an animal relates
      to its environment. 

PMID- 24896023
TI  - Cooperation in primates: Critical analysis of behavioural criteria.
AB  - Concerning hunting in chimpanzees, cooperation has generally been attributed to
      the behaviour of two or more individuals acting together to achieve a common goal
      (Boesch and Boesch, 1989). The common goal is often considered as the concrete
      result of a common action by two or several individuals. Although this result
      could be used as a criterion for cooperation, it could also be an outcome due to
      chance. We suggest that the goal, viewed as a concrete benefit shared by the
      partners, is not a requisite of cooperation but rather a possible consequence of
      a common action largely submitted to social constraints. Individuals engaged in a
      cooperative task in order to solve a problem have to exchange information to
      adjust to each other's behaviour. However, evidence of communication between
      partners during simultaneous cooperation is rare. An experiment in which two
      chimpanzees each had to simultaneously pull a handle to get a fruit was
      performed. We analysed not only the concrete result of the partners' activity but
      also what the individuals took into account before pulling a handle. We tried to
      specify what the chimpanzees learned by means of a series of logical propositions
      which we were able to confront the experimental results. 

PMID- 24896024
TI  - A comparative analysis of spatial memory processes.
AB  - This paper reviews spatial memory processes in three highly evolved taxa:
      hymenoptera, birds and mammals. In these three taxa, the goal location can be
      memorized egocentrically as a vector specifying the head-referred direction and
      the distance to the goal, and/or exocentrically as a view specifying the spatial
      layout of the surrounding landmarks perceived by the animal when standing at the
      goal. The egocentric coding process requires a path-integration mechanism to
      update the memorized goal location as a function of the animal's current
      position. Changes of direction are estimated allothetically (by reference to an
      external compass) in hymenoptera, idiothetically (on the basis of internal
      movement-related information) in mammals, and probably in both ways in birds.
      Computer simulations have shown that path-integration is very sensitive to random
      errors occurring in idiothetic but not in allothetic estimations. When using the
      exocentric coding process, hymenoptera store the bearings and angular sizes of
      landmarks in a compass-oriented colour snapshot taken at the goal. They may then
      return to the goal by moving so as to reduce the discrepancy between the current
      view of landmarks and the memorized snapshot. In mammals, this process can be
      accounted for by a neurobiologically plausible model which highlights the
      fundamental role of exploration of the environment. The way this process is
      implemented in birds is less clear. 

PMID- 24896025
TI  - Joint memory.
AB  - Joint memory is defined as the property of a social group in actualizing its own
      past transformations. It may result from the coupling of individual memories or
      be inscribed in the external environment. The concept of joint memory becomes
      heuristic when it subsumes an ensemble of social processes that are sufficiently
      integrated to be treated as an entity belonging to the real world. In social
      insects, colonies can perform action-perception loops which give rise to
      collective outcomes based on past experience; selective pressures could favour
      individual behavioural algorithms the combination of which provides a historical
      record organizing activities both in space and time. In contrast, social groups
      do not appear sufficiently autonomous in most vertebrates for joint memory be
      more than a way of seeing collective performances. However, in human beings, the
      development of external representations has made possible the growth of a
      socially distributed cognition; the accumulation of epigenetic events through
      cultural processes produces a set of material and symbolic products that feed
      back upon the conditions of evolution of the species. 

PMID- 24896026
TI  - Perception and learning in evolution.
AB  - Different theoretical models and methods exist which help to tackle the question
      of perception and learning in evolution. Waddington's genetic assimilation and
      its counterpart, the 'Wright Effect', provide a good methodological framework for
      experiments and simulations. Comparative analysis, in which phylogenetic as well
      as ecological aspects are considered, is another useful tool. These approaches
      consider cognitive processes with their simultaneous involvement in selective
      processes; they say very little about their emergence. 

PMID- 24896027
TI  - A profound disparity revisited: Perception and judgment of abstract identity
      relations by chimpanzees, human infants, and monkeys.
AB  - We review the evidence for three important disparities involving the perception
      and judgment of identity relations by human and nonhuman primates. First, only
      humans beyond infancy and adult chimpanzees (Pan troglodytes) with a history of
      language or token training can explicitly judge relations (same or different)
      between relations (identity and nonidentity) in a matching-to-sample (MTS) task.
      Second, both human and chimpanzee infants perceive relational similarity as
      measured in preference-for-novelty tasks. The human and chimpanzee infants,
      however, do not express this tacit knowledge in judgmental tasks like relational
      MTS. Third, unlike the human and chimpanzee infants, adult rhesus monkeys (Macaca
      mulatta) tested with the same preference-for-novelty tasks do not perceive
      abstract relational similarities and differences despite their sensitivity to
      physical identity. 

PMID- 24896028
TI  - Ecological correlates of social learning: problems and solutions for the
      comparative method.
AB  - Interspecific variation in learning and cognition is often accounted for by
      adaptive specialization, an ecological framework where variation between species
      in the environmental problems they face is thought to select for quantitatively
      and/or qualitatively different abilities. Adaptive specialization theory relies
      on the comparative method for testing its hypotheses and assumes a naturally
      selected basis for the predicted differences. This review examines social
      learning as a specialization to group-living and scramble feeding competition. It
      points out one important problem with current studies in the area, the lack of
      quantitative controls for confounding variables that may cause type 1 or 2 error
      in comparative tests. A linear regression technique is proposed to measure and
      remove interspecific differences on control tests for which there is no predicted
      adaptive specialization; as in other areas of comparative biology, the adaptive
      prediction is then made on the residual deviation from the regression of these
      confounding variables. Examples are given from research on opportunistic
      Columbids, the group-living feral pigeon Columbia livia, and the territorial
      Zenaida dove, Zenaida aurita. 

PMID- 24896029
TI  - Evolutionary implications of neural circuit structure and function.
AB  - Recent physiological studies of neural circuits have shown that single circuits
      can produce more than one behavior, and that different circuits can combine to
      produce a single, new behavior. Because neural circuits are multifunctional and
      highly integrated, they are expected to evolve relatively slowly. Comparative
      studies of invertebrates and vertebrates have confirmed this expectation, as
      circuit structure and motor pattern output are generally conserved relative to
      peripheral morphological structures. These findings suggest that behavioral
      evolution may also be relatively conservative. Information about neural circuit
      structure and function also has implications for our understanding of
      morphological and brain evolution. In particular, the conserved nature of neural
      circuits may contribute to evolutionary change in peripheral structures, and to
      the gradual increase in nervous system size over evolutionary time. 

PMID- 24896030
TI  - Evaluating genetic models of cognitive evolution and behaviour.
AB  - Cognitive evolution can be studied at several different levels, ranging from
      complex societies of interdependent persons to the DNA molecules coding for
      enzymes that synthesize neurotransmitter molecules. Genetic models of cognitive
      evolution can be fairly evaluated only if they involve one or two genetic loci,
      maybe three loci if a massive investment of resources is made. If a simple
      genetic model is seriously proposed, it ought to be tested by genetic linkage
      analysis so that future theorizing can be guided and constrained by facts. For
      more complex behavioural characteristics based on large numbers of genes and
      intricate interrelations with the environment, genetic analysis and genetic
      theories are not likely to yield conclusive results. Instead, studying individual
      differences in the brain and neural correlates of cognitive processes will likely
      provide more rapid progress toward a deeper understanding of evolution. 

PMID- 24896031
TI  - Niche construction, genetic evolution and cultural change.
AB  - In evolution, adaptation is traditionally viewed as a process by which natural
      selection moulds organisms to fit pre-established environmental templates. The
      changes organisms cause in environments are seldom thought evolutionarily
      significant. However, organisms partly create their own environments by 'niche
      construction'. A formal model of niche construction is discussed. It focusses on
      two genetic loci, E and A. It assumes: This model produces some surprising
      results. For example, timelags occur between the spread of niche construction and
      the response to the selection it generates. Niche construction also enhances the
      role of phenotypes in evolution. Organisms not only carry and propagate genes,
      but they also modify the selection pressures that select those genes. This dual
      role changes the relationship between genetic evolution; individual development;
      learning; and cultural processes in human beings. 

PMID- 24896032
TI  - Non-genetic transmission of information: Candidate cognitive processes and the
      evolution of culture.
AB  - The evolution of dual-inheritance systems, specifically the evolution of human
      culture, are considered as evolutionary events of profound significance. In this
      paper I adopt the view commonly held amongst biologists in recent years that
      human cultural change can be fruitfully understood as cultural evolution. Such an
      approach does not deny the possibility of understanding cultural change from
      other viewpoints. It does, however, have the advantage of having to be couched in
      explicitly psychological terms. Using the replicator-interactor theory of Dawkins
      and Hull I explore what cognitive mechanisms might be identified as having the
      properties of a replicator, and how reconstructions of human evolution may help
      in identifying such mechanisms. 

PMID- 24896033
TI  - Trial and error in the evolution of cognition.
AB  - This essay samples evolutionary epistemology, ideas about formative influences of
      behavior in evolution, and recent work in animal learning. It does so to
      illustrate how contrasting conceptions of science - as beginning in
      presuppositionless observation, and as conjecture and refutation - can be
      compared to views about how trial and error processes have entered into the
      evolution of animal cognitive capacities. Campbell's argument that visual
      perception arose as a means of vicarious locomotory trial and error, due to
      coincidence between the visual spectrum and penetrability, is contrasted with
      Wachtershauser's case for a prior coincidence between visual sensitivity and the
      wavelengths capable of driving photosynthesis. The Darwinian picture of organisms
      as passive products of chance variation and natural selection is contrasted with
      the views of Popper, Waddington and Gottlieb, according to which animals may take
      the evolutionary initiative by generating behavioral novelty. In the study of
      learning operant and respondent conditioning contrast with regard to the
      active/passive comparison, but recent work has shown that associative learning
      can involve active computational processing, and that both types of learning are
      bound by historically imposed constraints. One such constraint may be modularity,
      which Fodor takes to imply that scientific observation can be theory-neutral.
      This view is opposed by Churchland, who argues that, even at the level of
      observational description, science is a process of trial and error, in which the
      trials always involve theoretical assumptions. 

PMID- 24896034
TI  - Cognitive ethology, vigilance, information gathering, and representation: Who
      might know what and why?
AB  - Cognitive ethology, a relatively new interdisciplinary and integrative science,
      is under attack with respect to its scientific status. However, there also are
      strong supporters of research in this area. In this paper I consider My study of
      vigilance indicates that the way in which individuals are positioned with respect
      to one another influences their behavior, and that when a flock contains four or
      more birds there are large changes in scanning and other patterns of behavior
      that may be related to how grosbeaks attempt to gather information about other
      flock members. When birds are arranged in a circular array so that they can see
      one another easily compared to when they are arranged in a line that makes visual
      monitoring of flock members more difficult, birds who have difficulty seeing one
      another are These differences in behavior argue against the pooling of data
      collected on individuals feeding in different geometric arrays. The variations in
      behavior also may say something about if and how individuals attempt visually to
      represent their group to themselves-how they form, store, and use records of the
      behavior of others to inform their own future behavior. 

PMID- 24896035
TI  - Cognition and evolution - an organization of action perspective.
AB  - It is argued that the term 'cognition' should be used to refer to a particular
      class of behavioural process involving off-line representation of the world. The
      evolutionary advantage of such processing in terms of flexibility in the
      production of behaviour is discussed as well as disadvantages in terms of speed
      and cost. The advantages and disadvantages of alternative processes are also
      discussed. In developing the argument, cognition is related to motivation and
      affect. 

PMID- 24896036
TI  - Mental symbols and genetic symbols: Analogies between theoretical perspectives in
      biology and cognitive science.
AB  - A striking parallel may be drawn between the historical succession of explanatory
      theories of life and explanatory theories of cognitive phenomena. In both domains
      independently, approaches to understanding the problem of adaptation spawned the
      concept of formal representation: in biology the representation of hereditary
      characters by genes, and in psychology the symbolic representation of mental
      contents by computational states. Molecular biology and classical cognitivism now
      share the same problem of the origin of language (genetic code and language of
      thought) and the assignment of content to manipulated symbols. Such isomorphism
      of the problems and their modes of resolution could provide grounds for criticism
      of the naive way in which biology is used to solve the difficulties encountered
      in psychology, as in the teleological approach to intentionality. On the other
      hand, acceptance of the analogy implies that any solution or major revision in
      one domain should be able to inspire equivalent solutions or revisions in the
      other. 

PMID- 24896037
TI  - Cued and detached representations in animal cognition.
AB  - This paper analyzes the function of certain aspects of cognition, like planning,
      deceiving, self-awareness, and communication. I distinguish between two kinds of
      representations of information. A cued representation stands for something that
      is present in the current situation. Detached representations stand for objects
      or events that are neither present in the situation nor triggered by some recent
      situation. The inner environment of an animal is defined as the collection of all
      detached representations. The fundamental difference between signals and symbols
      is that the reference of a symbol is a detached representation, while a signal
      refers to a cued representation. Detached representations make planning possible.
      I distinguish between immediate planning, where plans are made for present needs,
      and anticipatory planning, where future needs are predicted. The evolution of
      self-consciousness is outlined as a series of steps. The first is when other
      agents are seen as having an inner environment of their own. This is when
      deception becomes possible. A further step is when the agent realizes that the
      other agents' representations of the external world includes a representation of
      the inner environment of the agent itself. Then the agent can become self
      conscious since it can form representations of its own representations. 

PMID- 24896038
TI  - Intentionality and evolution.
AB  - Three conditions are, according to Dretske, necessary for representations to be
      causal in an organism's behavior, and typically not fulfilled by phylogenetic
      representations: Condition c is first discussed: it is argued that, in some
      plausible interpretation of 'system as a whole', at least some types of
      information can shape behavior in a teleological way without being available to
      the system 'as a whole'. Then condition b is shown not to provide in itself any
      way of establishing the privileged status of learning over other kinds of
      flexible, information-driven processes in goal-oriented behaviors. A third
      section examines the notion of present versus past causal roles, which are
      supposed respectively to belong to informational contents and to genetic plans.
      To this, it is objected that learned correlations share with phylogenetic
      representations such a temporal gap and that informational content did play a
      role in recruiting a particular phylogenetic representation to control motor
      output. 

PMID- 24896039
TI  - The relation between causality and explanation in emergentist naturalistic
      theories of cognition.
AB  - According to the orthodox viewpoint of the cognitive sciences, psychological
      explanations are generally considered to be causal explanations. The dualistic
      philosophy underpinning this position, implying a strict separation between the
      physical and the symbolic, reveals itself as depending on a purely formal view of
      causality. The current naturalistic theories of meaning and cognition were
      developed first and foremost on the basis of this formal approach, and aimed at
      explaining cognitive phenomena and phenomena of meaning as proceeding from
      physical or material properties. We propose to analyze the relation between
      causality and explanation in the case of a subgroup of the latter theories,
      namely those that conceive of the physical and/or biological genesis of meaning
      and cognition in terms of emergence, and in particular the morphodynamical theory
      of Jean Petitot. On the basis of arguments from current theories of causal
      explanation on the one hand, and non-reductive physicalism on the other hand, we
      show that this emergentist naturalistic approach cannot fulfill the explanatory
      ambitions it sets forth. Firstly, current causal approaches of explanation imply
      the idea that contents are 'pre-packaged', and hence assume that there is a basic
      level of causality. Secondly, nonreductive physicalism shows in what sense the
      combination of an ontological monism (the belief in a basic level of causality)
      and an explanatory dualism implies a major paradox. We will show that the attempt
      to add a causal dimension - i.e., the dimension of the origin of meaning and
      cognition, viewed as causally determinative - combined with an emergentist
      conception of the relation between levels, leads to major limitations on the
      level of explanation. 

PMID- 24896040
TI  - Introducing anthropomorphism, discontinuities and anecdotes to question them.
AB  - Recourse to anthropomorphism, folk psychology, or discontinuist thought, in order
      to take into account the richness of animal cognitive processes and of their
      evolution, is of some heuristic value. However, in the absence of recognised
      criteria allowing the hypothesised behavioural discontinuities between species to
      be tested and alternative interpretations of anecdotal reports to be selected,
      there is considerable risk that these alternatives will be ideological rather
      than scientific. A 'clinical analysis' of this anthropomorphism and discontinuist
      'symptom' allows us to unravel its ideological aspect, namely the wishful
      thinking and the 'egomorphism' of a subject projecting a wishful representation
      of himself onto one who is not ego, and in turn to investigate its heuristic
      value in ethnological, psychopathological or animal behavioural studies. This
      analysis leads us to propose some tools: 

PMID- 24896041
TI  - Cognition = life: Implications for higher-level cognition.
AB  - Any global consideration of the theme 'Evolution and Cognition' requires a clear
      definition of what we mean by the term 'cognition'. In contemporary cognitive
      science, there are two distinct paradigms with contrasting definitions of
      cognition. The computational theory of mind is based on the syntaxical
      manipulation of symbolic representations; this paradigm is objectivist because
      the postulate of a unique independent reality is necessary as a referential basis
      for semantic grounding of the symbols. The alternative 'constructivist' paradigm
      is based on the biological metaphor 'cognition = life' and programmatically
      follows the evolution of cognition from bacteria to civilized humans; it is non
      objectivist. There is a definite tendency to consider that the computational
      theory is appropriate for 'high-level' human cognition, whereas the
      constructivist approach is appropriate for 'low-level' cognition. This article
      argues against such a division of labour, since the issue of objectivism is a
      watershed which continues to demarcate the computational and constructivist
      paradigms in their respective approaches to higher-level cognition. 

PMID- 24896042
TI  - Continuous glucose monitoring during a 100-km race: a case study in an elite
      ultramarathon runner.
AB  - The current case study intended to measure blood glucose fluctuation in 2
      marathon runners during a 100-km race using a continuous glucose-monitoring
      system (CGMS) and investigate the relationship between glucose profile and change
      in running speed. Two experienced ultramarathon runners participated in this
      study. A CGMS glucose sensor was inserted into the subcutaneous abdominal tissue
      at 35 h before the 100-km race, and the glucose profile was monitored
      continuously until the end of the race. Race pace and energy intake during the
      race were recorded. Participants finished the race in 6h:51min:17s (runner A) and
      8h:56min:04s (runner B), and the race-pace decrement ratios were 17.6% for runner
      A and 27.2% for runner B. The average relative intensity throughout the 100-km
      race was 89.9% +/- 5.8% lactate threshold (LT) in runner A and 78.4% +/- 8.6% LT
      in runner B. The total amount of carbohydrate intake during the race was 249 g
      and 366 g in runners A and B, respectively. Despite lower carbohydrate intake,
      runner A maintained a normal glucose level throughout the race, while runner B
      rapidly decreased blood glucose and became hypoglycemic after the 80-km point.
      These results suggest that elite ultramarathon runners may have the ability to
      prevent a large decrement in blood glucose level regardless of the amount of
      energy intake during the race to maintain higher relative running intensity. 

PMID- 24896043
TI  - [Global governance for health].

PMID- 24896044
TI  - Thalidomide and its analogues: comparative clinical efficacy and safety, and cost
      effectiveness.

PMID- 24896045
TI  - [Antiretroviral therapy in HIV-infected children and adolescents: lessons learned
      in 30 years of the epidemic].
AB  - This study aims to evaluate antiretroviral therapy in children and adolescents
      with AIDS. We selected 247 abstracts published from 1983 to 2013, collected from
      the PubMed and LILACS databases. Sixty-nine articles were selected. Attention to
      research in the pediatric age bracket in 30 years of the epidemic is explained by
      the age group's immunological characteristics, since AIDS progresses faster in
      children than in adults. Recent studies focus on the initiation of highly active
      antiretroviral therapy before the onset of symptoms. Early introduction of
      combination antiretroviral therapy has been implemented effectively and safely in
      populations with limited resources, leading to significantly improved survival.
      The current challenge is to manage a chronic disease with acute complications.
      New studies should focus on population specificities and identify the individual
      needs of pediatric patients.

PMID- 24896046
TI  - Trends in epidemiology in the 21st century: time to adopt Bayesian methods.
AB  - 2013 marked the 250th anniversary of the presentation of Bayes' theorem by the
      philosopher Richard Price. Thomas Bayes was a figure little known in his own
      time, but in the 20th century the theorem that bears his name became widely used
      in many fields of research. The Bayes theorem is the basis of the so-called
      Bayesian methods, an approach to statistical inference that allows studies to
      incorporate prior knowledge about relevant data characteristics into statistical
      analysis. Nowadays, Bayesian methods are widely used in many different areas such
      as astronomy, economics, marketing, genetics, bioinformatics and social sciences.
      This study observed that a number of authors discussed recent advances in
      techniques and the advantages of Bayesian methods for the analysis of
      epidemiological data. This article presents an overview of Bayesian methods,
      their application to epidemiological research and the main areas of epidemiology
      which should benefit from the use of Bayesian methods in coming years.

PMID- 24896047
TI  - Syphilis in pregnancy and congenital syphilis in Amazonas State, Brazil: an
      evaluation using database linkage.
AB  - This study analyzes notification of syphilis in pregnancy and congenital syphilis
      in Amazo- nas State, Brazil, from 2007 to 2009 and verifies underreporting in
      databases in the National Information System on Diseases of Notification (SINAN)
      and the occurrence of perinatal deaths associated with congenital syphilis and
      not reported in the Mortality Information System (SIM). This was a cross
      sectional study with probabilistic record linkage between the SINAN and SIM.
      There were 666 reports of syphilis in pregnant women, including 224 in 2007
      (3.8/1,000), 244(4.5/1,000) in 2008, and 198(4.0/1,000) in 2009. The study found
      486 cases of congenital syphilis, of which 153 in 2007 (2.1/1,000), 193 in 2008
      (2.6/1,000), and 140 in 2009 (2.0/1,000). After linkage of the SINAN databases,
      237 pregnant women (35.6%) had cases of congenital syphilis reported. The SIM
      recorded 4,905 perinatal deaths, of which 57.8% were stillbirths. Probabilistic
      record linkage between SIM and SINAN-Congenital Syphilis yielded 13 matched
      records. The use of SINAN and SIM may not reflect the total magnitude of
      syphilis, but provide the basis for monitoring and analyzing this health problem,
      with a view towards planning and management.

PMID- 24896049
TI  - [Mobility, traffic accidents, and associated factors among Guatemalan university
      students].
AB  - The aim of this study was to identify and quantify the association between the
      amount of driving (km/year), traffic accidents, and other factors among
      university students in Guatemala. A cross-sectional study was performed during
      the 2010-2011 school year in a sample of 1,016 drivers who completed a self
      administered questionnaire that assessed mobility patterns, use of safety
      accessories, driving style, and automobile crashes. The results showed a positive
      association between amount of driving and greater involvement in risky driving
      (adjusted regression coefficient 3.25, 95%CI: 2.23-4.27, for the highest level of
      exposure). More frequent involvement in risky driving and older age showed the
      strongest associations with traffic accidents. Although the amount of driving was
      positively associated with a higher accident rate, most of this association was
      found to be mediated by involvement in risky driving practices.

PMID- 24896048
TI  - Acceptability of self-conducted home-based HIV testing among men who have sex
      with men in Brazil: data from an on-line survey.
AB  - The Brazilian HIV/AIDS epidemic is concentrated among men who have sex with men
      (MSM), however HIV testing rates among MSM are not commensurate with their risk.
      Strategies to expand early diagnosis may include use of self-conducted home-based
      testing kits, which are now available for purchase in the US. In April 2011 we
      conducted a survey with Brazilian MSM using Facebook to assess HIV testing
      preferences and acceptability of home-based testing. Among 356 previously tested,
      HIV-negative MSM, 47% reported a preference for home-based testing, 27% preferred
      clinic-based testing, and 26% had no preference. Less frequent testers and those
      who had considered testing but failed to test were more likely to prefer home
      based testing. Close to 90% reported that they would use self-test kits; 62% and
      54% said they would use home-based testing to make choices about unprotected sex
      with regular and new partners, respectively. Concerns included difficulty to
      understand the tests (32%) and receiving results alone (23%). Overall, home-based
      testing may appeal to MSM and result in increased testing frequency. Research on
      feasibility and utilization of self-tests in practice is needed.

PMID- 24896050
TI  - [Investigation of vectors and reservoirs in an acute Chagas outbreak due to
      possible oral transmission in Aguachica, Cesar, Colombia].
AB  - Colombia recorded 11 cases of acute Chagas disease and 80 cases of oral
      contamination with Trypanosoma cruzi. The current study analyzes the
      entomological and parasitological characteristics of the outbreak in Aguachica,
      Cesar Department, in 2010. An interdisciplinary group of health professionals and
      regional university personnel conducted the laboratory tests in the patients and
      the investigation of the transmission focus. Eleven cases of acute Chagas
      diseases were detected in a single family in a dwelling with domiciliated
      triatomines and Rhodnius pallescens, Pantrongylus geniculatus, Eratyrus
      cuspidatus, and two Didelphis marsupialis opossums infected with T. cruzi in
      Attalea butyracea and Elaeis oleifera palm trees in the urban area of Aguachica.
      The study analyzes the role of R. pallescens and palm trees in the wild cycle of
      T. cruzi and in oral transmission of Chagas disease. Sporadic incursions by wild
      R. pallescens, P. geniculatus, and E. cuspidatus from the nearby palm trees into
      human dwellings may cause increasingly frequent outbreaks of oral Chagas disease.

PMID- 24896051
TI  - [Oral health satisfaction among Brazilian elderly: a gender study using a
      hierarchical model].
AB  - The objectives of this study were to identify gender differences in relation to
      factors associated with oral health satisfaction among the elderly and to
      estimate the prevalence of edentulism by gender and age. The study included 2,052
      elderly (>= 60 years) residing in Sete Lagoas, Minas Gerais State, Brazil.
      Poisson regression was used to estimate prevalence of edentulism. The association
      between oral health satisfaction and independent variables was estimated using
      ordinal regression with a hierarchical multidimensional model. Prevalence rates
      for edentulism in males and females were 63% and 68.8%, respectively. Most
      elderly males (63%) and females (57%) were satisfied with their oral health. The
      final adjusted model for both genders consisted of variables related to
      environmental characteristics, health behaviors, and oral health conditions. The
      study concludes that oral satisfaction is heavily influenced by oral health
      status and health behaviors, while the associated factors differ by gender.

PMID- 24896052
TI  - [Factors associated with regular cigarette smoking by adolescents from public
      schools in Londrina, Parana, Brazil].
AB  - This cross-sectional epidemiological study aimed to identify factors associated
      with regular cigarette smoking among adolescents. The sample included 517 public
      school 9th graders in Londrina, Parana State, Brazil. A structured questionnaire
      was used to collect information, including social and demographic
      characteristics, social relations, and health risk behaviors. Logistic regression
      was used in the statistical analysis, with significance set at 5%. 8.9% of the
      adolescents reported smoking at least one cigarette a day in the previous 30
      days. Age >= 15 years (OR = 2.28; 95%CI: 1.21-4.32; p = 0.011) and having friends
      that smoked (OR = 12.62; 95%CI: 4.44-35.89; p < 0.0001) were associated with
      regular smoking in both the univariate and multivariate analyses. Meanwhile,
      gender, race, social class, living with father and mother, religion, maternal
      education, having tried alcohol, physical activity, and paid work were not
      associated with smoking. These findings support the development of community
      based tobacco control strategies targeting adolescents.

PMID- 24896053
TI  - An entomoepidemiological investigation of Chagas disease in the state of Ceara,
      Northeast Region of Brazil.
AB  - The seroprevalence of Chagas disease in humans and the presence of triatomines
      were investigated in a rural locality in the State of Ceara, Brazil, an
      historically endemic region. Approximately 80% of the surveyed residents agreed
      to undergo serological tests. Intradomestic and peridomestic environments were
      searched for triatomines in both the dry and rainy seasons. The prevalence rate
      of Chagas disease was 1.2% and the majority of individuals confirmed with the
      disease over 50 years of age. A total of 761 specimens of triatomines were
      captured, most of which were from colonies composed of nymphs and adult bugs, and
      the majority of specimens were obtained in the dry season. Triatoma brasiliensis
      was the predominant species. Analysis using light microscopy revealed that 28.6%
      of the insects were Trypanosoma cruzi positive. Results suggest that peridomestic
      man-made structures, such as animal shelters, improper storage of timber and
      uninhabited dwellings contribute to the high rate of triatomine infestation in
      the area.

PMID- 24896054
TI  - Substance use and sexual risk among at-risk adolescents in Juiz de Fora, Minas
      Gerais State, Brazil.
AB  - We examined the difference in prevalence of substance use and sexual risk
      behaviors among at-risk youth participants in programs offered by community-based
      organizations in Juiz de Fora, Minas Gerais State, Brazil, by gender and
      organization type (governmental vs. non-governmental). 388 adolescents were
      recruited from 25 intervention-based organizations servicing at-risk youth
      between the ages of 12 and 17 in Juiz de Fora. Participants completed a 15-item
      survey assessing substance use and sexual risk behaviors, along with socio
      demographic predictors of these behaviors. Males were more likely to report drug
      and alcohol use associated with homelessness and abandonment. Females were more
      likely to report sexual risk taking associated with neighborhood crime.
      Participants from non-governmental organizations were less likely to engage in
      all measured risk behaviors. The present analysis points to the need to
      understand how Brazil's Child and Adolescent Act is being applied and the
      implications this has for intervention and the promotion of positive health
      outcomes for young people.

PMID- 24896055
TI  - [Health practices by teams from Street Outreach Offices].
AB  - Two distinctly serious public health problems interconnect in the universe of
      this study: living on the streets and drug use. To deal with this problem, Street
      Outreach Offices were created with a prime focus on the life world of drug users
      living on the streets. The aim was to learn about the health practices used by
      teams from Street Outreach Offices, in addition to describing their work
      strategies, learning about the health education provided by the teams, and
      unveiling their feelings about the work process on the streets. This was a
      qualitative study with participant observation and content analysis as proposed
      by Bardin. Analysis of interviews with 15 participants revealed five thematic
      categories. Health practices by the teams prioritized outreach to (and
      embracement of) people living on the streets, reinforcing the importance of
      users' participation and interdisciplinary, inter-sector work.

PMID- 24896056
TI  - [Self-reported hypertension and non-adherence to continuous-use medication in
      Brazil: a population-based study].
AB  - The aim of this study was to estimate the prevalence of non-adherence to several
      continuous-use drugs by patients 30 to 79 years of age with self-reported
      hypertension, and associated factors, drawing on data from the Brazilian National
      Sample Household Survey (PNAD-2008). Prevalence ratios (PR) and respective 95%
      confidence intervals (95%CI) were obtained by Poisson regression. The proportion
      of individuals that failed to adhere to continuous-use medication was 17%.
      Characteristics directly associated with non-adherence were: male gender,
      residence in the North, Northeast, or Central-West of Brazil, and smoking. Non
      adherence decreased with age, per capita family income, number of chronic
      diseases, and medical consultation in the previous 12 months, and was inversely
      associated with 11 or more years of schooling (PR = 0.92; 95%CI: 0.86-0.98), not
      working and not being unemployed, and physical activity. Adherence to
      antihypertensive medication is necessary and requires investment in primary care,
      improved access to health services, and measures to offset regional, social, and
      gender inequalities.

PMID- 24896057
TI  - [Social support and physical activity in adolescents from public schools: the
      importance of family and friends].
AB  - The aim of this study was to verify the association between different types and
      sources of social support and physical activity among adolescents from Curitiba,
      Parana State, Brazil. A school-based survey was conducted with a representative
      sample of adolescents from public schools (n = 1,469). Multiple regression models
      were used to test the association between weekly frequency and sources of social
      support from family and friends and weekly frequency of physical activity. Among
      boys, frequent company of family (PR: 2.88; 95%CI: 2.00-4.13) and friends (PR:
      5.46; 95%CI: 2.33-12.78) and positive reinforcement from friends (PR: 1.81;
      95%CI: 1.18-2.77) were positively associated with physical activity. Sporadic
      invitation by the family was negatively associated with physical activity (PR:
      0.66; 95%CI: 0.46-1.14). For girls, frequent company of family (PR: 3.39; 95%CI:
      1.49-7.69) and friends (PR: 4.06; 95%CI: 2.22-7.45) increased the likelihood of
      physical activity. Company of friends was the most important type of social
      support for physical activity among these adolescents.

PMID- 24896058
TI  - [The development of evaluation capacity in primary healthcare management: a case
      study in Santa Catarina State, Brazil, 2008-2011].
AB  - This article analyzes evaluation capacity-building based on the case study of a
      State Health Secretariat participating in the Project to Strengthen the Technical
      Capacity of State Health Secretariats in Monitoring and Evaluating Primary
      Healthcare. The case study adopted a mixed design with information from
      documents, semi-structured interviews, and evaluation of primary care by the
      State Health Secretariat in 2008-2011. Process analysis was used to identify the
      logical events that contributed to evaluation capacity-building, with two
      categories: evaluation capacity-building events and events for building
      organizational structure. The logical chain of events was formed by negotiation
      and agreement on the decision-making levels for the continuity of evaluation,
      data collection and analysis by the State Health Secretariat, a change in key
      indicators, restructuring of the evaluation matrix, and communication of the
      results to the municipalities. The three-way analysis showed that the aim of
      developing evaluation capacity was achieved.

PMID- 24896059
TI  - [Forum: health and indigenous peoples in Brazil. Introduction].
AB  - This Forum on Health and Indigenous Peoples in Brazil explores contemporary
      challenges to indigenous health and health politics in Brazil. The short
      collection of articles that follow are based on presentations, originally given
      at the Indigenous Health Working Group panel at the 10th Brazilian Public Health
      Conference in Rio Grande do Sul State, by professors Carlos E. A. Coimbra Jr.
      (Escola Nacional de Saude Publica, Fundacao Oswaldo Cruz), Marina Denise Cardoso
      (Universidade Federal de Sao Carlos) and Eliana E. Diehl (Universidade Federal de
      Santa Catarina) with Marcos A. Pellegrini (Universidade Federal de Roraima). In
      this short Introduction, I introduce these contributions, taking as a point of
      reference a local example of healthcare inequity derived from a presentation at
      the same panel by Paulo F. Supretapra, indigenous community leader from
      Etenhiritipa village, Mato Grosso State.

PMID- 24896060
TI  - [Health and indigenous peoples in Brazil: reflections based on the First National
      Survey of Indigenous People's Health and Nutrition].
AB  - The current configuration of indigenous peoples' health in Brazil results from a
      complex historical trajectory, responsible for major delays for this population
      segment in the countrywide social advances seen in recent decades, particularly
      in the fields of health, education, housing, and sanitation. The main focus of
      this contribution is to review synthetically a selection of the main results of
      the First National Survey of Indigenous People's Health and Nutrition, conducted
      in the period 2008-2009, which visited 113 villages across the Brazil and
      interviewed 6,692 women and 6,128 children. Among the results, emphasis is given
      to the observed poor sanitation conditions in villages, high prevalence of
      chronic malnutrition, anemia, diarrhea, and acute respiratory infections in
      children, and the emergence of non-communicable chronic diseases in women. The
      scenario depicted by this survey requires urgent critical review of indigenous
      health policy in order to better meet the health needs of Brazil's indigenous
      population.

PMID- 24896061
TI  - [Health and indigenous peoples in Brazil: notes on some current policy mistakes].
AB  - This article aims to analyze health policies for indigenous peoples in Brazil
      with reference to the 1988 National Constitution and its consequences for their
      healthcare. Three components are central to this analysis: the management model,
      based on the concepts of "autonomy" and "social control", but essentially
      expressing the forms of indigenous representation and participation in public
      policies; the concept of "differential care" for establishing an inclusive (but
      operationally normative) healthcare model; and the relationship between the
      management model for indigenous healthcare and indigenous therapeutic practices.

PMID- 24896062
TI  - [Health and indigenous peoples in Brazil: the challenge of professional training
      and continuing education of workers in intercultural contexts].
AB  - This article discusses training and continuing medical education for indigenous
      health workers and health professionals in indigenous health under the guidelines
      of the Brazilian National Healthcare Policy for Indigenous Peoples, which is
      currently behind schedule and incomplete as part of the official government
      agenda. Based on inter-sector proposals for health training by the Ministries of
      Health and Education, the article highlights the case of indigenous healthcare,
      emphasizing that government initiatives in this area still need to incorporate
      the concept of continuing education, a powerful tool for fostering intercultural
      dialogue and orienting health practices.

PMID- 24896063
TI  - [Forum: health and indigenous people in Brazil. Postscript].

PMID- 24896064
TI  - [Portuguese-language cultural adaptation of the Items Banks of Anxiety and
      Depression of the Patient-Reported Outcomes Measurement Information System
      (PROMIS)].
AB  - The Patient-Reported Outcome Measurement Information System (PROMIS), structured
      in Itens Banks, provides a new tool for evaluating results that apply to various
      chronic diseases through advanced statistical techniques (TRI) and computerized
      adaptive testing (CAT). The aim of this study was to culturally adapt the Items
      Banks of Anxiety and Depression of PROMIS to the Portuguese language. The process
      followed the recommendations of PROMIS through the advanced translation,
      reconciliation, back-translation, FACIT review, independent review, finalization,
      pre-test, and incorporation of the results from the pre-test. The translated
      version was pre-tested in ten patients, and items 3, 46, and 53 of the Bank of
      Anxiety and item 46 of the bank of Depression had to be changed. Changes affected
      equivalence of meaning, and the final version was consistent with the Brazilian
      population's linguistic and cultural skills. In conclusion, for the Brazilian
      population the translated version proved semantically and conceptually equivalent
      to the original.

PMID- 24896065
TI  - [Use of personal protective equipment for motorcycle taxi drivers: perception of
      risks and associated factors].
AB  - This study aimed to examine the practices and perceptions of motorcycle taxi
      drivers concerning the use of personal protective equipment (PPE), based on field
      research and an exploratory and descriptive qualitative approach. Thirty
      motorcycle taxi drivers from Jequie, Bahia State, Brazil, were interviewed. Data
      collection used a semi-structured interview and questionnaire. Data were analyzed
      using thematic content analysis. The results showed: Category 1 - risk
      perception, subcategory conditioning/determinant factors for the use of PPE;
      Category 2 - adherence, subcategory adherence to the use of personal protective
      equipment; Category 3 - PPE as a protective factor against traffic accidents,
      subcategories 1 - work-related accidents, 2 - use of PPE at the time of the
      accident, 3 - non-use of PPE at the time of the accident. Finally, motorcycle
      taxi drivers clearly have some knowledge of personal protective equipment and
      even acknowledge the importance of its use, despite not always using it properly.

PMID- 24896066
TI  - [Counterfeit and contraband drugs in Brazil: overview and prospects for
      preventing their use].
AB  - The problem of counterfeit medicines is increasing rapidly, aggravated by
      globalization and the lure of profit from this illegal activity. Various types of
      drugs have been counterfeited, posing a serious public health and safety problem.
      The current article provides an overview of the issue in Brazil and the resulting
      measures taken by the National Health Surveillance Agency (ANVISA) in
      collaboration with the Federal Police from 2007 to March 2011. The study analyzed
      seizures of counterfeit drugs, arrests, and other factors. No professional
      pharmacist was present in 90% of the establishments were some type of crime
      occurred (sale of counterfeit drugs and lack of control of narcotics and other
      drugs). Among the products seized, most were drugs for erectile dysfunction. The
      study showed the importance of inter-agency collaboration for combatting this
      type of irregular drug sales.

PMID- 24896068
TI  - Graphene-quantum-dot nonvolatile charge-trap flash memories.
AB  - Nonvolatile flash-memory capacitors containing graphene quantum dots (GQDs) of 6,
      12, and 27 nm average sizes (d) between SiO2 layers for use as charge traps have
      been prepared by sequential processes: ion-beam sputtering deposition (IBSD) of
      10 nm SiO2 on a p-type wafer, spin-coating of GQDs on the SiO2 layer, and IBSD of
      20 nm SiO2 on the GQD layer. The presence of almost a single array of GQDs at a
      distance of ~13 nm from the SiO2/Si wafer interface is confirmed by transmission
      electron microscopy and photoluminescence. The memory window estimated by
      capacitance-voltage curves is proportional to d for sweep voltages wider than  +/
      3 V, and for d = 27 nm the GQD memories show a maximum memory window of 8 V at a
      sweep voltage of  +/- 10 V. The program and erase speeds are largest at d = 12
      and 27 nm, respectively, and the endurance and data-retention properties are the
      best at d = 27 nm. These memory behaviors can be attributed to combined effects
      of edge state and quantum confinement. 

PMID- 24896069
TI  - Estimating Young's modulus of graphene with Raman scattering enhanced by
      micrometer tip.
AB  - We demonstrate that the Raman intensities of G and 2D bands of a suspended
      graphene can be enhanced using a gold tip with an apex size of 2.3 MUm. The
      enhancement decays with the tip-graphene distance exponentially and remains
      detectable at a distance of 1.5 MUm. Raman mappings show that the enhanced area
      is comparable to the apex size. Application of a bias voltage to the tip can
      attract the graphene so that Raman signals are intensified. The exponential
      enhancement-distance relationship enables the measurement of the graphene
      deformation, and the Young's modulus of graphene is estimated to be 1.48 TPa. 

PMID- 24896070
TI  - The role of teriparatide in sequential and combination therapy of osteoporosis.
AB  - Osteoporosis is complicated by the occurrence of fragility fractures. Over past
      years, various treatment options have become available, mostly potent
      antiresorptive agents such as bisphosphonates and denosumab. However,
      antiresorptive therapy cannot fully and rapidly restore bone mass and structure
      that has been lost because of increased remodelling. Alternatively recombinant
      human parathyroid hormone (rhPTH) analogues do increase the formation of new bone
      material. The bone formation stimulated by intermittent PTH analogues not only
      increases bone mineral density (BMD) and bone mass but also improves the
      microarchitecture of the skeleton, thereby reducing incidence of vertebral and
      nonvertebral fractures. Teriparatide, a recombinant human PTH fragment available
      in Switzerland, is reimbursed as second-line treatment in postmenopausal women
      and men with increased fracture risk, specifically in patients with incident
      fractures under antiresorptive therapy or patients with glucocorticoid-induced
      osteoporosis and intolerance to antiresorptives. This position paper focuses on
      practical aspects in the management of patients on teriparatide treatment.
      Potential first-line indications for osteoanabolic treatment as well as the
      benefits and limitations of sequential and combination therapy with
      antiresorptive drugs are discussed. 

PMID- 24896071
TI  - The preclinical development of regorafenib for the treatment of colorectal
      cancer.
AB  - INTRODUCTION: The RAS-RAF-MEK-ERK pathway is one of the best characterized kinase
      cascades. During the exploration of small molecules that inhibit RAF1 kinase,
      regorafenib (BAY 73-4506) was discovered as a multikinase inhibitor which
      demonstrated anti-cancer, anti-angiogenic, and apoptotic activities in metastatic
      colorectal cancer. This was not the first multikinase inhibitor discovered for
      the disease; indeed, before regorafenib was approved by FDA as a multikinase
      inhibitor for metastatic colorectal cancer in 2012, sorafenib (BAY 43-9006) had
      already been developed to be the first in the world as a multikinase inhibitor
      for malignancy. Indeed, the only difference between the two compounds is fluorine
      bound to its proximal phenyl ring although the end result is a considerably
      different profile, both as a kinase inhibitor as well as in its clinical
      application. AREAS COVERED: In this drug discovery case history, the authors
      review the design, discovery, and development of both regorafenib and sorafenib
      from back in the 1990s. Furthermore, the authors highlight the drug's anti-cancer
      and anti-angiogenic properties as well as its efficacy, safety pharmacology and
      toxicology based on FDA documents. EXPERT OPINION: In order to better predict the
      efficacy of kinase inhibitors and to utilize them more efficiently, our
      understanding of drug discovery, the approaches for kinase profiling, and
      technologies needed for their development are paramount. Indeed, the authors
      believe that the field should better explore the use of predictive biomarkers
      that might be able to better assess these therapeutics. Pharmaceutical scientists
      must also consider the cost effectiveness of the targeted agents developed as a
      number of the drugs developed are very expensive.

PMID- 24896073
TI  - Developmental changes in associations among timber wolf (Canis lupus) postures.
AB  - I examined developmental changes in associations among components of timber wolf
      (Canis lupus) postural communication in two hand-reared pups between 15 and 85
      days of age. The frequency with which select postural components co-occurred was
      scored from 180 randomly sampled frames of video records of these pups made
      during social interactions. I used this index of association as the basis for
      multidimensional scaling and cluster analyses. Relations among postural
      components became more structured with age. Two-dimensional models were found to
      account for associations among postures displayed at 69-85 and 32-67 days of age
      but not at 15-32 days of age. I interpret these orthogonal dimensions as continua
      of dominance to submission and seriousness to playfulness. These data suggest the
      intended messages contained in postural displays may depend on the specific
      combinations of components used. 

PMID- 24896074
TI  - Transverse patterning in pigeons.
AB  - The ability of pigeons to form configural stimulus representations was assessed
      in two operant discrimination experiments. In Experiment 1 the transverse
      patterning problem of Spence (1952) was trained. In Phase 1, subjects had to
      choose stimulus A on A + B - trials; B + C - trials were added in Phase 2. In
      Phase 3, the first two pairs were combined with C + A - trials. The success of
      the subjects was simulated by a model assuming that elemental and configural
      stimulus representations coexist in a stable proportion, even in the phases of
      the experiment which do not require configural stimulus representations for
      successful solution. Experiment 2 replicated the first two phases of Experiment
      1, but trained A + C - in Phase 3. Comparison of the results of this experiment
      with simulations of the model showed that elemental and configural stimulus
      representations coexisted in similar proportions as in Experiment 1, even though
      they were not necessary for successful task solution. 

PMID- 24896075
TI  - Unexplained sexual segregation in polygamous ungulates: a defense of an
      ontogenetic approach.
AB  - Two processes are generally mixed when considering ungulate sexual segregation:
      the social segregation which appears to be a rule in polygamous ungulate species
      and the spatial segregation which is facultative. Early in life, there is
      evidence that males and females exhibit different levels of activity and patterns
      of interaction which could lead to behavioural incompatibility. It is proposed
      that juvenile females, differently motivated than males to interact socially, may
      soon avoid the pseudo-sexual and agonistic male behavioural components. as body
      and behavioural dimorphism increase with age, the behavioural incompatibility
      would be intensified. Since adults often interact agonistically with or avoid
      them, juveniles will attend to interact with same-sex peers of similar status.
      Because social experiences are occurring since early stages of development, i.e.,
      during sensitive periods, a social auto-segregation by sex/age classes is
      expected. Then population would be structured in coherent socio-spatial sets of
      compatible individuals, sharing similar constraints and properties. Around the
      birth period, females become asocial promoting a temporal social segregation.
      Costs linked to gestation and lactation may make females more dependent on water
      and rich food resources. Female with offspring are also likely to select areas
      where the risks of predation are reduced, sometimes at detriment to energy
      intake, while other animals exhibit opportunistic feeding behaviour, resulting in
      seasonally ecological segregation. Body growth channels a lot of energy for males
      which are expected to use the best feeding areas. However, indirect competition
      for the same resources may result in a spatial segregation between the sexes. Sex
      and age-specific activity budgets are suspected to favour social and spatial
      segregations. The social segregation among males and females use exclusive
      ranges. Whether spatial segregation results in ecological segregation would
      however depend on habitat heterogeneity, population density, local ecological
      conditions and the biological cycle periods. It is suggested that spatial
      segregation will occur not only between the sexes but also among males. If
      populations are structured in coherent socio-spatial units, spatial segregation
      among individuals of age and sex classes may result from indirect interactions
      between sets of individuals (of same age and sex class), that may be translated
      as an indirect competition between individuals. Studies on ethogenesis are
      considered as fundamental as they allow to know on what basis social and spatial
      segregations are set up. In particular, studies on behavioural development could
      highlight how social segregation between adults may result from a process that
      originates much earlier in the life of animals. By considering the role of
      behaviour, we defend the idea that social and spatial segregations may be
      logically distinguished. 

PMID- 24896076
TI  - Temporal evolution of vigilance in roe deer.

PMID- 24896077
TI  - Auditory distance estimation in song birds: Implications, methodologies and
      perspectives.
AB  - Acoustic signals such as bird song degrade progressively during atmospheric
      propagation and consequently provide information about the distance of the
      signaler. Information on the signaler's distance is particularly important for
      animals that use acoustic signals to defend a territory or, in general, to
      regulate their spacing. Male territorial song birds can use this information to
      assess the distance of a conspecific singer (called 'ranging'). This ability
      presumably increases the efficiency of defending a territory because it enables a
      territory holder to discriminate among threatening intruders and distant
      conspecifics without interrupting current behavior to, for instance, spend time
      and energy in approaching. There are a variety of factors that can influence the
      outcome of 'ranging experiments' of which some are discussed here. So far,
      playback experiments in the field that impeded close-range experience of subjects
      with the loudspeaker yielded the clearest evidence for ranging. Flights of
      subjects to positions beyond the loudspeaker in response to playback of degraded
      songs provide unambiguous evidence for over-estimation of distance of degraded
      songs and thus reduce problems of interpretation encountered in experiments that
      allow subjects' close-range experience with the loudspeaker. Furthermore, the
      accuracy of ranging can be influenced by the kind of degradation and the
      availability of song features that facilitate its assessment so that these
      factors, in addition to an appropriate playback design, should be taken into
      account in future experiments. 

PMID- 24896078
TI  - Responses of collared doves to playback of coos.
AB  - Dove coos are assumed to play an important role in territorial defence and mate
      attraction. Playback experiments of coos may provide insight into their
      information content. In a pilot experiment, territorial males responded strongly
      to playback of perch coos. We were able to quantify the response by three
      behavioural measurements. A second series of playback showed that the
      experimental set-up and the behavioural measurements were suitable to demonstrate
      the perception of a difference between two distinctive versions of a perch coo. A
      stronger response was elicited by coos containing modulated elements. 

PMID- 24896072
TI  - Bisphenol a and reproductive health: update of experimental and human evidence,
      2007-2013.
AB  - BACKGROUND: In 2007, an expert panel reviewed associations between bisphenol A
      (BPA) exposure and reproductive health outcomes. Since then, new studies have
      been conducted on the impact of BPA on reproduction. OBJECTIVE: In this review,
      we summarize data obtained since 2007, focusing on a) findings from human and
      animal studies, b) the effects of BPA on a variety of reproductive end points,
      and c) mechanisms of BPA action. METHODS: We reviewed the literature published
      from 2007 to 2013 using a PubMed search based on keywords related to BPA and male
      and female reproduction. DISCUSSION: Because BPA has been reported to affect the
      onset of meiosis in both animal and in vitro models, interfere with germ cell
      nest breakdown in animal models, accelerate follicle transition in several animal
      species, alter steroidogenesis in multiple animal models and women, and reduce
      oocyte quality in animal models and women undergoing in vitro fertilization
      (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests
      that BPA is a uterine toxicant because it impaired uterine endometrial
      proliferation, decreased uterine receptivity, and increased implantation failure
      in animal models. BPA exposure may be associated with adverse birth outcomes,
      hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but
      additional studies are required to confirm these associations. Studies also
      suggest that BPA may be a testicular toxicant in animal models, but the data in
      humans are equivocal. Finally, insufficient evidence exists regarding effects of
      BPA on the oviduct, the placenta, and pubertal development. CONCLUSION: Based on
      reports that BPA impacts female reproduction and has the potential to affect male
      reproductive systems in humans and animals, we conclude that BPA is a
      reproductive toxicant.

PMID- 24896079
TI  - Rules of parameter variation in homotype series of birdsong can indicate a
      'sollwert' significance.
AB  - Various bird species produce songs which include homotype pattern series, i.e.
      segments composed of a number of repeated vocal units. We compared such units and
      analyzed the variation of their parameters, especially in the time and the
      frequency domain. In addition, we examined whether and how serial changes of both
      the range and the trend of variation were related to song constituents following
      the repetitions. Data evaluation showed that variation of specific serial
      parameters (e.g., unit pitch or unit duration) occurring in the whistle song
      types of nightingales (Luscinia megarhynchos) were converging towards a distinct
      terminal value. Although song-types differed in this terminal value, it was found
      to play the role of a key cue ('sollwert'). The continuation of a song depended
      on a preceding attainment of its specific 'sollwert'. Our results suggest that
      the study of signal parameters and rules of their variations make a useful tool
      for the behavioral access to the properties of the control systems mediating
      serial signal performances. 

PMID- 24896080
TI  - Temporal and structural features of infant calls in relation to caregiving
      behaviour in common marmosets, Callithrix j. jacchus.
AB  - The role of infants in the communal rearing system of marmosets and tamarins has
      received little attention although their demands may not be complied by
      inadequate helpers. As acoustic signalling plays an important role in their
      social communication, it is expected to be an effective way for infants to signal
      their demand for care. As a first approach, this study focussed on the use and
      quality of 'tsik' calls given by infants of common marmosets (Callithrix j.
      jacchus) in the context of caregiving. The acoustic and non-acoustic behaviour of
      a group of common marmosets were recorded during the first two weeks of the life
      of two infants (twins). Vocalizations were classified, and the structure of the
      infants' 'tsik' calls was quantified by measuring specific signal parameters.
      Infants gave 'tsik' calls in close temporal relation to caregiving behaviour.
      Specific parameters covaried with the subsequent behaviour of potential
      caretakers. Values of call duration, start frequency, peak frequency, and range
      were lower when infants' calls were followed by no reaction or an approach of
      group members, whereas these parameters showed higher values when followed by a
      transfer of infants. Our results suggest that the actual demand of infants is
      encoded in the variations of 'tsik' calls. 

PMID- 24896081
TI  - Temporal structure of red jungle fowl crow sequences: single-case analysis.
AB  - Vocalisations can be indicators of the physical state or condition of an animal,
      for instance the crow of a rooster. There are no published data on the temporal
      structure of crow sequences. In this paper 536 crows in 22 sequences of one red
      jungle fowl rooster (rooster 1) were recorded and analysed. Calls were very
      characteristic and there was little variation between the calls. Rooster 1 crowed
      with a mean latency of 287 s after onset of a light in the early morning. The
      average crow sequence consisted of 29 calls which lasted for 1416 ms on average.
      A gradual increase in pre-call interval was characteristic of each sequence. The
      variation in note durations is systematic and especially the last note correlated
      highly with the total call duration. Both the pre-call interval and the duration
      of the 4th note (doooo) may be parameters of fatigue and thus of physical
      condition. The number of crows in a sequence was positively related to air
      pressure outdoors. An experiment is done in which the physical condition of a
      rooster (rooster 2) is manipulated by food deprivation. The results are analysed
      with single case randomisation tests. The number of crows in a sequence is
      significantly reduced after food deprivation, while the pre-call intervals are
      significantly increased. Prediction of the number of crows in the sequence can be
      done on base of the pre-call interval of the second call: both rooster 1 and 2
      showed long pre-call intervals in short call sequences. Food deprivation and the
      possible loss of condition have a significant effect on the temporal structure of
      crow sequences and cause a decrease in the number of crows in a call sequence. 

PMID- 24896082
TI  - Postoperative radiotherapy for glioma: improved delineation of the clinical
      target volume using the geodesic distance calculation.
AB  - OBJECTS: To introduce a new method for generating the clinical target volume
      (CTV) from gross tumor volume (GTV) using the geodesic distance calculation for
      glioma. METHODS: One glioblastoma patient was enrolled. The GTV and natural
      barriers were contoured on each slice of the computer tomography (CT) simulation
      images. Then, a graphic processing unit based on a parallel Euclidean distance
      transform was used to generate the CTV considering natural barriers. Three
      dimensional (3D) visualization technique was applied to show the delineation
      results. Speed of operation and precision were compared between this new
      delineation method and the traditional method. RESULTS: In considering spatial
      barriers, the shortest distance from the point sheltered from these barriers
      equals the sum of the distance along the shortest path between the two points;
      this consists of several segments and evades the spatial barriers, rather than
      being the direct Euclidean distance between two points. The CTV was generated
      irregularly rather than as a spherical shape. The time required to generate the
      CTV was greatly reduced. Moreover, this new method improved inter- and intra
      observer variability in defining the CTV. CONCLUSIONS: Compared with the
      traditional CTV delineation, this new method using geodesic distance calculation
      not only greatly shortens the time to modify the CTV, but also has better
      reproducibility.

PMID- 24896084
TI  - A possible method for non-Hermitian and Non-PT-symmetric Hamiltonian systems.
AB  - A possible method to investigate non-Hermitian Hamiltonians is suggested through
      finding a Hermitian operator eta+ and defining the annihilation and creation
      operators to be eta+ -pseudo-Hermitian adjoint to each other. The operator eta+
      represents the eta+ -pseudo-Hermiticity of Hamiltonians. As an example, a non
      Hermitian and non-PT-symmetric Hamiltonian with imaginary linear coordinate and
      linear momentum terms is constructed and analyzed in detail. The operator eta+ is
      found, based on which, a real spectrum and a positive-definite inner product,
      together with the probability explanation of wave functions, the orthogonality of
      eigenstates, and the unitarity of time evolution, are obtained for the non
      Hermitian and non-PT-symmetric Hamiltonian. Moreover, this Hamiltonian turns out
      to be coupled when it is extended to the canonical noncommutative space with
      noncommutative spatial coordinate operators and noncommutative momentum operators
      as well. Our method is applicable to the coupled Hamiltonian. Then the first and
      second order noncommutative corrections of energy levels are calculated, and in
      particular the reality of energy spectra, the positive-definiteness of inner
      products, and the related properties (the probability explanation of wave
      functions, the orthogonality of eigenstates, and the unitarity of time evolution)
      are found not to be altered by the noncommutativity. 

PMID- 24896085
TI  - Augmenting the post-transplantation growth and survivorship of juvenile
      scleractinian corals via nutritional enhancement.
AB  - Size-dependent mortality influences the recolonization success of juvenile corals
      transplanted for reef restoration and assisting juvenile corals attain a refuge
      size would thus improve post-transplantation survivorship. To explore colony size
      augmentation strategies, recruits of the scleractinian coral Pocillopora
      damicornis were fed with live Artemia salina nauplii twice a week for 24 weeks in
      an ex situ coral nursery. Fed recruits grew significantly faster than unfed ones,
      with corals in the 3600, 1800, 600 and 0 (control) nauplii/L groups exhibiting
      volumetric growth rates of 10.65 +/- 1.46, 4.69 +/- 0.9, 3.64 +/- 0.55 and 1.18
      +/- 0.37 mm3/week, respectively. Corals supplied with the highest density of
      nauplii increased their ecological volume by more than 74 times their initial
      size, achieving a mean final volume of 248.38 +/- 33.44 mm3. The benefits of
      feeding were apparent even after transplantation to the reef. The corals in the
      3600, 1800, 600 and 0 nauplii/L groups grew to final sizes of 4875 +/- 260 mm3,
      2036 +/- 627 mm3, 1066 +/- 70 mm3 and 512 +/- 116 mm3, respectively. The fed
      corals had significantly higher survival rates than the unfed ones after
      transplantation (63%, 59%, 56% and 38% for the 3600, 1800, 600 and 0 nauplii/L
      treatments respectively). Additionally, cost-effectiveness analysis revealed that
      the costs per unit volumetric growth were drastically reduced with increasing
      feed densities. Corals fed with the highest density of nauplii were the most cost
      effective (US$0.02/mm3), and were more than 12 times cheaper than the controls.
      This study demonstrated that nutrition enhancement can augment coral growth and
      post-transplantation survival, and is a biologically and economically viable
      option that can be used to supplement existing coral mariculture procedures and
      enhance reef restoration outcomes.

PMID- 24896083
TI  - MicroRNA profiling as tool for in vitro developmental neurotoxicity testing: the
      case of sodium valproate.
AB  - Studying chemical disturbances during neural differentiation of murine embryonic
      stem cells (mESCs) has been established as an alternative in vitro testing
      approach for the identification of developmental neurotoxicants. miRNAs represent
      a class of small non-coding RNA molecules involved in the regulation of neural
      development and ESC differentiation and specification. Thus, neural
      differentiation of mESCs in vitro allows investigating the role of miRNAs in
      chemical-mediated developmental toxicity. We analyzed changes in miRNome and
      transcriptome during neural differentiation of mESCs exposed to the developmental
      neurotoxicant sodium valproate (VPA). A total of 110 miRNAs and 377 mRNAs were
      identified differently expressed in neurally differentiating mESCs upon VPA
      treatment. Based on miRNA profiling we observed that VPA shifts the lineage
      specification from neural to myogenic differentiation (upregulation of muscle
      abundant miRNAs, mir-206, mir-133a and mir-10a, and downregulation of neural
      specific mir-124a, mir-128 and mir-137). These findings were confirmed on the
      mRNA level and via immunochemistry. Particularly, the expression of myogenic
      regulatory factors (MRFs) as well as muscle-specific genes (Actc1, calponin,
      myosin light chain, asporin, decorin) were found elevated, while genes involved
      in neurogenesis (e.g. Otx1, 2, and Zic3, 4, 5) were repressed. These results were
      specific for valproate treatment and--based on the following two observations-
      most likely due to the inhibition of histone deacetylase (HDAC) activity: (i) we
      did not observe any induction of muscle-specific miRNAs in neurally
      differentiating mESCs exposed to the unrelated developmental neurotoxicant sodium
      arsenite; and (ii) the expression of muscle-abundant mir-206 and mir-10a was
      similarly increased in cells exposed to the structurally different HDAC inhibitor
      trichostatin A (TSA). Based on our results we conclude that miRNA expression
      profiling is a suitable molecular endpoint for developmental neurotoxicity. The
      observed lineage shift into myogenesis, where miRNAs may play an important role,
      could be one of the developmental neurotoxic mechanisms of VPA.

PMID- 24896087
TI  - Prevalence of WHO transmitted drug resistance mutations by deep sequencing in
      antiretroviral-naive subjects in Hunan Province, China.
AB  - BACKGROUND: There are few data on the prevalence of WHO transmitted drug
      resistance mutations (TDRs) that could affect treatment responses to first line
      antiretroviral therapy (ART) in Hunan Province, China. OBJECTIVE: Determine the
      prevalence of WHO NRTI/NNRTI/PI TDRs in ART-naive subjects in Hunan Province by
      deep sequencing. METHODS: ART-naive subjects diagnosed in Hunan between 2010-2011
      were evaluated by deep sequencing for low-frequency HIV variants possessing WHO
      TDRs to 1% levels. Mutations were scored using the HIVdb.stanford.edu algorithm
      to infer drug susceptibility. RESULTS: Deep sequencing was performed on samples
      from 90 ART-naive subjects; 83.3% were AE subtype. All subjects had advanced
      disease (average CD4 count 134 cells/mm3). Overall 25.6%(23/90) of subjects had
      HIV with major WHO NRTI/NNRTI TDRs by deep sequencing at a variant frequency
      level >= 1%; 16.7%(15/90) had NRTI TDR and 12.2%(11/90) had a major NNRTI TDR.
      The majority of NRTI/NNRTI mutations were identified at variant levels <5%.
      Mutations were analyzed by HIVdb.stanford.edu and 7.8% of subjects had variants
      with high-level nevirapine resistance; 4.4% had high-level NRTI resistance. Deep
      sequencing identified 24(27.6%) subjects with variants possessing either a PI TDR
      or hivdb.stanford.edu PI mutation (algorithm value >= 15). 17(19.5%) had PI TDRs
      at levels >1%. CONCLUSIONS: ART-naive subjects from Hunan Province China infected
      predominantly with subtype AE frequently possessed HIV variants with WHO
      NRTI/NNRTI TDRs by deep sequencing that would affect the first line ART used in
      the region. Specific mutations conferring nevirapine high-level resistance were
      identified in 7.8% of subjects. The majority of TDRs detected were at variant
      levels <5% likely due to subjects having advanced chronic disease at the time of
      testing. PI TDRs were identified frequently, but were found in isolation and at
      low variant frequency. As PI/r use is infrequent in Hunan, the existence of PI
      mutations likely represent AE subtype natural polymorphism at low variant level
      frequency.

PMID- 24896088
TI  - Virus versus host plant microRNAs: who determines the outcome of the interaction?
AB  - Considering the importance of microRNAs (miRNAs) in the regulation of essential
      processes in plant pathogen interactions, it is not surprising that, while plant
      miRNA sequences counteract viral attack via antiviral RNA silencing, viruses in
      turn have developed antihost defense mechanisms blocking these RNA silencing
      pathways and establish a counter-defense. In the current study, computational and
      stem-loop Reverse Transcription - Polymerase Chain Reaction (RT-PCR) approaches
      were employed to a) predict and validate virus encoded mature miRNAs (miRs) in 39
      DNA-A sequences of the bipartite genomes of African cassava mosaic virus (ACMV)
      and East African cassava mosaic virus-Uganda (EACMV-UG) isolates, b) determine
      whether virus encoded miRs/miRs* generated from the 5'/3' harpin arms have the
      capacity to bind to genomic sequences of the host plants Jatropha or cassava and
      c) investigate whether plant encoded miR/miR* sequences have the potential to
      bind to the viral genomes. Different viral pre-miRNA hairpin sequences and viral
      miR/miR* length variants occurring as isomiRs were predicted in both viruses.
      These miRNAs were located in three Open Reading Frames (ORFs) and in the
      Intergenic Region (IR). Moreover, various target genes for miRNAs from both
      viruses were predicted and annotated in the host plant genomes indicating that
      they are involved in biotic response, metabolic pathways and transcription
      factors. Plant miRs/miRs* from conserved and highly expressed families were
      identified, which were shown to have potential targets in the genome of both
      begomoviruses, representing potential plant miRNAs mediating antiviral defense.
      This is the first assessment of predicted viral miRs/miRs* of ACMV and EACMV-UG
      and host plant miRNAs, providing a reference point for miRNA identification in
      pathogens and their hosts. These findings will improve the understanding of host-
      pathogen interaction pathways and the function of viral miRNAs in Euphorbiaceous
      crop plants. 

PMID- 24896089
TI  - Function and interaction of the coupled genes responsible for Pik-h encoded rice
      blast resistance.
AB  - Pik-h, an allele of Pik, confers resistance against the rice blast pathogen
      Magnaporthe oryzae. Its positional cloning has shown that it comprises a pair of
      NBS-LRR genes, Pikh-1 and Pikh-2. While Pikh-1 appears to be constitutively
      transcribed, the transcript abundance of Pikh-2 responds to pathogen challenge.
      The Pikh-1 CC (coiled coil) domain interacts directly with both AvrPik-h and Pikh
      2. Transient expression assays demonstrated that Pikh-2 mediates the initiation
      of the host defence response. Nucleocytoplasmic partitioning of both Pikh-1 and
      Pikh-2 is required for their functionalities. In a proposed mechanistic model of
      Pik-h resistance, it is suggested that Pikh-1 acts as an adaptor between AvrPik-h
      and Pikh-2, while Pikh-2 transduces the signal to trigger Pik-h-specific
      resistance. 

PMID- 24896090
TI  - Regeneration of Solanum nigrum by somatic embryogenesis, involving frog egg-like
      body, a novel structure.
AB  - A new protocol was established for the regeneration of Solanum nigrum by frog egg
      like bodies (FELBs), which are novel somatic embryogenesis (SE) structures
      induced from the root, stem, and leaf explants. The root, stem, and leaf explants
      (93.33%, 85.10%, and 100.00%, respectively) were induced to form special
      embryonic calli on Murashige and Skoog (MS) medium containing 1.0 mg/L 2,4
      dichlorophenoxyacetic acid, under dark condition. Further, special embryonic
      calli from the root, stem, and leaf explants (86.97%, 83.30%, and 99.47%,
      respectively) were developed into FELBs. Plantlets of FELBs from the three
      explants were induced in vitro on MS medium supplemented with 5.0 mg/L 6
      benzylaminopurine and 0.1 mg/L gibberellic acid, and 100.00% plantlet induction
      rates were noted. However, plantlet induction in vivo on MS medium supplemented
      with 20 mg/L thidiazuron showed rates of 38.63%, 15.63%, and 61.30% for the root,
      stem, and leaf explants, respectively, which were lower than those of the in
      vitro culture. Morphological and histological analyses of FELBs at different
      development stages revealed that they are a novel type of SE structure that
      developed from the mesophyll (leaf) or cortex (stem and root) cells of S. nigrum.

PMID- 24896091
TI  - Panepoxydone targets NF-kB and FOXM1 to inhibit proliferation, induce apoptosis
      and reverse epithelial to mesenchymal transition in breast cancer.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is a highly diverse group that
      is associated with an aggressive phenotype. Its treatment has been challenging
      due to its heterogeneity and absence of well-defined molecular targets. Thus,
      there is an urgent need to identify novel agents with therapeutic application. NF
      kappaB is over-expressed in many breast cancers; thus, inactivation of the NF
      kappaB pathway could serve as a therapeutic target. Here we report for the first
      time the anti-tumor activity of panepoxydone (PP), a NF-kappaB inhibitor isolated
      from an edible mushroom, in several breast cancer cell lines. METHODS: We
      investigated the effects of PP on cell growth, migration-invasion, apoptosis and
      EMT-related proteins expression in MCF-7 and TNBC cell lines MDA-MB-231, MDA-MB
      468 and MDA-MB-453. RESULTS: Significant antitumor activity was seen in all cell
      lines, with differential responses noted in cell-line specific manner. Treatment
      with PP resulted in significant cytotoxicity, decreased invasion, migration and
      increased apoptosis in all cell lines tested. Up-regulation of Bax and cleaved
      PARP and down-regulation of Bcl-2, survivin, cyclin D1 and caspase 3 were noted
      in PP-treated breast cancer cells. The antitumor effect of PP appeared related to
      its ability to inhibit the phosphorylation of inhibitor of NF-kappaB
      (IkappaBalpha) with cytoplasmic accumulation. PP treatment also down-regulated
      FOXM1 which resulted in a reversal of EMT. Similar results were obtained after
      silencing of NF-kB and FOXM1. CONCLUSION: Altogether, these studies show, for the
      first time the antitumor activity of PP against breast cancer cells, in
      particular TNBC cells. Furthermore, it highlights the concept that optimal
      treatment of TNBC warrants attention to the differential sensitivity of various
      TNBC subtypes to therapeutic agents. These results suggest that the PP may be a
      potentially effective chemopreventive or therapeutic agent against breast cancer.
      However, additional studies are required to more fully elucidate the mechanism of
      antitumor effect of PP.

PMID- 24896093
TI  - Ubiquitous sialometabolism present among oral fusobacteria.
AB  - Fusobacterium nucleatum is a ubiquitous member of the human oral flora and is
      associated with the development of periodontitis and a variety of other types of
      polymicrobial infections of the mucosa. In the oral cavity, this species is one
      of the few that is prevalent in both healthy and diseased subgingival plaque.
      Using microarray analysis, we examined the transcriptional response of F.
      nucleatum subspecies nucleatum to whole blood in order to identify some of the
      genetic responses that might occur during the transition from health to disease.
      From these studies, we identified a sialic acid catabolism operon that was
      induced by the presence of blood. We subsequently confirmed that this operon was
      inducible by the presence of synthetic sialic acid, but we found no evidence
      suggesting sialic acid was used as a major carbon source. However, this organism
      was found to possess a de novo synthesized surface sialylation ability that is
      widely conserved among the various F. nucleatum subspecies as well as in F.
      periodonticum. We provide evidence that fusobacterial sialylation does occur in
      the oral cavity irrespective of health status. Interestingly, only a minority of
      fusobacterial cells exhibit surface sialylation within dental plaque, whereas
      most cells are uniformly sialylated when grown in pure culture. The implications
      of these results are discussed. 

PMID- 24896094
TI  - Plasma interleukin-27 (IL-27) levels are not modulated in patients with chronic
      HIV-1 infection.
AB  - OBJECTIVE: IL-27 is an immunomodulatory cytokine with potent anti-HIV properties
      in PBMCs, CD4+ T cells, macrophages and immature dendritic cells. Previous
      smaller studies have suggested that HIV-1 infection may alter IL-27 and influence
      HIV-1 pathogenesis. The aim of this study was to examine the relationship between
      plasma IL-27 levels in a well-characterised cohort of HIV-1 infected patients.
      METHODS: Patients were stratified into four groups based on HIV-1 viral load and
      matched according to age, gender and those receiving antiretroviral treatment. IL
      27 levels and C-reactive protein (CRP) were measured using
      electrochemiluminescence assays. D-dimer and CD4+ T cell counts were measured
      using an Enzyme Linked Fluorescence Assay and FACS, respectively. sCD14 and
      sCD163 were measured using ELISA. HIV-1 viral load was measured by bDNA or qRT
      PCR assays. RESULTS: Plasma IL-27 levels were measured in 505 patients (462 HIV+,
      43 controls). The mean level (+/-SEM) of IL-27 in controls was 2990.7+/-682.1
      pg/ml, in the <50 copies/ml group it was 2008.0+/-274.8 pg/ml, in the 51-10,000
      copies group it was 1468.7+/-172.3 pg/ml, in the 10,001-100,000 copies/ml group
      it was 1237.9+/-127.3 pg/ml and in the >100,000 copies/ml group it was 1590.1+/
      223.7 pg/ml. No statistically significant difference in IL-27 levels between
      groups were seen. There were no correlations noted between IL-27 and HIV-1 viral
      load or CD4+ T cell counts. There was a small correlation noted between D-dimer
      and IL-27 (Spearman r = 0.09, p = 0.03) and sCD163 and IL-27 (Spearman r = 0.12,
      p = 0.005). No correlation was observed between IL-27 and CRP or sCD14 levels.
      CONCLUSIONS: This is the largest study examining the levels of plasma IL-27 in
      HIV-1 infection. While IL-27 levels are not significantly altered in HIV-1
      infection compared to uninfected controls there may be a small association
      between IL-27 and D-dimer levels and IL-27 and sCD163 levels.

PMID- 24896095
TI  - Neutron exposures in human cells: bystander effect and relative biological
      effectiveness.
AB  - Bystander effects have been observed repeatedly in mammalian cells following
      photon and alpha particle irradiation. However, few studies have been performed
      to investigate bystander effects arising from neutron irradiation. Here we asked
      whether neutrons also induce a bystander effect in two normal human
      lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by
      targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV
      average neutron energy), and irradiated-cell conditioned media (ICCM) was
      transferred to unirradiated cells. The cytokinesis-block micronucleus assay was
      used to quantify genetic damage in radiation-naive cells exposed to ICCM from
      cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells
      grown in ICCM from irradiated cells showed no significant increase in the
      frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in
      ICCM from sham irradiated cells for either cell line. However, the neutron beam
      has a photon dose-contamination of 5%, which may modulate a neutron-induced
      bystander effect. To determine whether these low doses of contaminating photons
      can induce a bystander effect, cells were irradiated with cobalt-60 at doses
      equivalent to the percent contamination for each neutron dose. No significant
      increase in the frequencies of micronuclei or bridges was observed at these doses
      of photons for either cell line when cultured in ICCM. As expected, high doses of
      photons induced a clear bystander effect in both cell lines for micronuclei and
      bridges (p<0.0001). These data indicate that neutrons do not induce a bystander
      effect in these cells. Finally, neutrons had a relative biological effectiveness
      of 2.0 +/- 0.13 for micronuclei and 5.8 +/- 2.9 for bridges compared to cobalt
      60. These results may be relevant to radiation therapy with fast neutrons and for
      regulatory agencies setting standards for neutron radiation protection and
      safety.

PMID- 24896096
TI  - Preparation of anti-tumor nanoparticle and its inhibition to peritoneal
      dissemination of colon cancer.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is one of the most classic chemotherapy drugs.
      Nanoparticle drug delivery vehicles offer superiority over target effect
      enhancement and abatement of side effects. Little is known however as to the
      specific effect of nanoparticle on peritoneal dissemination of colon cancer. The
      aim of this study is to prepare one NPs (nanoparticles) loaded with 5-FU and
      investigate the characteristic of NPs and the role of it in peritoneal metastasis
      nodules formation of human colon cancer. METHODOLOGY/PRINCIPAL FINDINGS: Prepared
      the NPs (nanoparticles) loaded with 5-FU (5-Fluorouracil) by PEG-PLGA with the
      method of double emulsion. Then evaluate the characteristics of the NPs by
      scanning electron microscopy, analyzing the particle diameter distribution and
      determining the loading efficiency. Detect the release features of NPs in vitro
      and in vivo. Nude mice with peritoneal metastases were treated with 5-FU solution
      or 5-FU-NPs through peritoneal cavity. Count the nodules on peritoneum and
      mesenterium and survey the size of them. We got NPs with average-diameter of 310
      nm. In vitro release test shows NPs can release equably for 5 days with release
      rate of 99.2%. In vivo, NPs group can keep higher plasma concentration of 5-FU
      longer than it in solution group. The number of peritoneal dissemination nodule
      below 1 mm in 5-FU-sol group(17.3 +/- 3.5) and 5-FU-NP group(15.2 +/- 3.2) is
      less than control group(27.2 +/- 4.7)(P<0.05). The total number of nodules in 5
      FU-NP group(28.7 +/- 4.2) is significantly smaller than in 5-FU-sol group(37.7 +/
      6.3) (P<0.05). CONCLUSIONS/SIGNIFICANCE: The novel anti-tumor nanoparticles
      loaded with 5-FU by PEG-PLGA can release maintain 5 days and have inhibitory
      action to peritoneal dissemination of colon cancer in mice.

PMID- 24896097
TI  - SIRT6 is required for normal retinal function.
AB  - The retina is one of the major energy consuming tissues within the body. In this
      context, synaptic transmission between light-excited rod and cone photoreceptors
      and downstream ON-bipolar neurons is a highly demanding energy consuming process.
      Sirtuin 6 (SIRT6), a NAD-dependent deacylase, plays a key role in regulating
      glucose metabolism. In this study, we demonstrate that SIRT6 is highly expressed
      in the retina, controlling levels of histone H3K9 and H3K56 acetylation. Notably,
      despite apparent normal histology, SIRT6 deficiency caused major retinal
      transmission defects concomitant to changes in expression of glycolytic genes and
      glutamate receptors, as well as elevated levels of apoptosis in inner retina
      cells. Our results identify SIRT6 as a critical modulator of retinal function,
      likely through its effects on chromatin. 

PMID- 24896099
TI  - Deriving high-resolution protein backbone structure propensities from all crystal
      data using the information maximization device.
AB  - The most informative probability distribution functions (PDFs) describing the
      Ramachandran phi-psi dihedral angle pair, a fundamental descriptor of backbone
      conformation of protein molecules, are derived from high-resolution X-ray crystal
      structures using an information-theoretic approach. The Information Maximization
      Device (IMD) is established, based on fundamental information-theoretic concepts,
      and then applied specifically to derive highly resolved phi-psi maps for all 20
      single amino acid and all 8000 triplet sequences at an optimal resolution
      determined by the volume of current data. The paper shows that utilizing the
      latent information contained in all viable high-resolution crystal structures
      found in the Protein Data Bank (PDB), totaling more than 77,000 chains, permits
      the derivation of a large number of optimized sequence-dependent PDFs. This work
      demonstrates the effectiveness of the IMD and the superiority of the resulting
      PDFs by extensive fold recognition experiments and rigorous comparisons with
      previously published triplet PDFs. Because it automatically optimizes PDFs, IMD
      results in improved performance of knowledge-based potentials, which rely on such
      PDFs. Furthermore, it provides an easy computational recipe for empirically
      deriving other kinds of sequence-dependent structural PDFs with greater detail
      and precision. The high-resolution phi-psi maps derived in this work are
      available for download. 

PMID- 24896100
TI  - Do intergroup conflicts necessarily result from outgroup hate?
AB  - We developed a new experimental design to test whether or not individuals engage
      in conflict between social groups because they seek to harm outgroup members.
      Challenging prominent social psychological theories, we did not find support for
      such negative social preferences. Nevertheless, subjects heavily engaged in group
      conflict. Results support the argument that processes that act within social
      groups motivate engagement in conflict between groups even in the absence of
      negative social preferences. In particular, we found that "cheap talk"
      communication between group members fuels conflict. Analyses did not support the
      notion that the effect of communication results from guilt-aversion processes. 

PMID- 24896098
TI  - Early treatment with anti-VLA-4 mAb can prevent the infiltration and/or
      development of pathogenic CD11b+CD4+ T cells in the CNS during progressive EAE.
AB  - Natalizumab is a humanized monoclonal antibody against the leukocyte adhesion
      molecule very late antigen (VLA)-4, and is currently an approved therapy for
      patients with relapsing-remitting multiple sclerosis (RRMS). However, it is
      unknown whether natalizumab is beneficial for progressive forms of MS. Therefore,
      we assessed the effects of anti-VLA-4 monoclonal antibody (mAb) therapy in a
      progressive experimental autoimmune encephalomyelitis (EAE) mouse model. Notably,
      we found that early therapy could significantly reduce the severity of
      progressive EAE, while treatment initiated at an advanced stage was less
      efficient. Furthermore, we observed the accumulation of a novel subset of GM-CSF
      producing CD11b+CD4+ T cells in the CNS throughout disease progression.
      Importantly, early therapeutic anti-VLA-4 mAb treatment suppressed the
      accumulation of these GM-CSF-producing CD11b+CD4+ T cells in the CNS along with
      activated microglia/macrophages populations, and also conferred a protective
      effect against inflammation-mediated neurodegeneration, including demyelination
      and axonal loss. Collectively, our data suggest that early treatment with anti
      VLA-4 mAb can provide neuroprotection against progressive CNS autoimmune disease
      by preventing the accumulation of pathogenic GM-CSF-producing CD11b+CD4+ T cells
      in the CNS. 

PMID- 24896101
TI  - Accuracy of administratively-assigned ancestry for diverse populations in an
      electronic medical record-linked biobank.
AB  - Recently, the development of biobanks linked to electronic medical records has
      presented new opportunities for genetic and epidemiological research. Studies
      based on these resources, however, present unique challenges, including the
      accurate assignment of individual-level population ancestry. In this work we
      examine the accuracy of administratively-assigned race in diverse populations by
      comparing assigned races to genetically-defined ancestry estimates. Using 220
      ancestry informative markers, we generated principal components for patients in
      our dataset, which were used to cluster patients into groups based on genetic
      ancestry. Consistent with other studies, we find a strong overall agreement
      (Kappa  = 0.872) between genetic ancestry and assigned race, with higher rates of
      agreement for African-descent and European-descent assignments, and reduced
      agreement for Hispanic, East Asian-descent, and South Asian-descent assignments.
      These results suggest caution when selecting study samples of non-African and non
      European backgrounds when administratively-assigned race from biobanks is used. 

PMID- 24896104
TI  - Curcumin exerts inhibitory effects on undifferentiated nasopharyngeal carcinoma
      by inhibiting the expression of miR-125a-5p.
AB  - Curcumin suppresses proliferation, migration, invasion, metastasis and
      angiogenesis and induces apoptosis by regulating multiple signalling pathways and
      miRNAs in a wide variety of human malignancies. miRNAs play crucial roles in
      various steps of carcinogenesis in nasopharyngeal carcinoma (NPC); thus, they
      could serve as critical therapeutic targets for NPC treatment. Curcumin could
      provide a novel strategy to block or induce specific miRNAs for miRNA-based gene
      therapies. Nevertheless, there are no reports to date on the miRNAs regulated by
      curcumin in NPC. In the present study, we have carried out an miRNA microarray to
      identify the miRNAs regulated by curcumin in NPC. Curcumin treatment down
      regulated the expression of hsa-miR-125a-5p, hsa-miR-574-3p and hsa-miR-210 as
      determined by miRNA microarray analysis and qPCR (real-time quantitative reverse
      transcription-PCR). Forced expression of miR-125a-5p enhanced proliferation,
      migration and invasion of HONE1 cells. Primary NPC exhibited a significantly
      higher expression level of miR-125a-5p than healthy controls. miR-125a-5p
      inhibited the expression of tumour protein 53 (TP53), and curcumin treatment up
      regulated the expression of TP53. Taken together, these results indicate that
      curcumin exerted inhibitory effects on NPC by inhibiting the expression of miR
      125a-5p and, subsequently, enhancing the expression of TP53. Curcumin could
      provide a novel strategy to block miR-125a-5p for miRNA-based gene therapies in
      NPC. 

PMID- 24896105
TI  - Air travellers' awareness of the preventability of otic barotrauma.
AB  - OBJECTIVE: Otic barotrauma is common among air travellers and can cause severe
      otalgia, perforation of the tympanic membrane and hearing loss. Many prevention
      measures exist, with varying evidence to support their use. There are no data to
      establish if air travellers are aware of them or indeed use them. We aimed to
      establish air travellers' knowledge of such prevention measures. METHODS: We
      surveyed air travellers at two UK airports by means of a questionnaire. Answers
      to the questionnaire were collected over a two-week period. RESULTS: Overall, 179
      air travellers with a mean age of 28 years (range: 15-72 years) completed the
      questionnaire. There were 66 female and 113 male air travellers. The majority (84
      per cent) complained of symptoms while flying and 30 per cent were not aware of
      any prevention measures. Barotrauma-related symptoms were reported in 25 per cent
      of air travellers who were unaware of any prevention measures. Nearly all air
      travellers (86 per cent) indicated that more information regarding prevention
      measures would be useful. CONCLUSION: Air travellers are often not aware of
      prevention measures to avoid otic barotrauma, and the majority suffer as a
      result. Increasing public awareness of simple prevention measures would have a
      significant impact on air travellers.

PMID- 24896103
TI  - Characterization of desmoglein expression in the normal prostatic gland.
      Desmoglein 2 is an independent prognostic factor for aggressive prostate cancer.
AB  - PURPOSE: The expression of desmogleins (DSGs), which are known to be crucial for
      establishing and maintaining the cell-cell adhesion required for tissue
      integrity, has been well characterized in the epidermis and hair follicle;
      however, their expression in other epithelial tissues such as prostate is poorly
      understood. Although downregulation of classical cadherins, such as E-cadherin,
      has been described in prostate cancer tissue samples, the expression of
      desmogleins has only been previously reported in prostate cancer cell lines. In
      this study we characterized desmoglein expression in normal prostate tissues, and
      further investigated whether Desmoglein 2 (DSG2) expression specifically can
      serve as a potential clinical prognostic factor for patients diagnosed with
      primary prostate cancer. EXPERIMENTAL DESIGN: We utilized immunofluorescence to
      examine DSG2 expression in normal prostate (n = 50) and in a clinically well
      characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2
      expression with clinico-pathological characteristics and biochemical recurrence
      was analyzed to assess its clinical significance. RESULTS: These studies revealed
      that DSG2 and DSG4 were specifically expressed in prostatic luminal cells,
      whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not
      expressed in normal prostate epithelium. Further analyses of DSG2 expression in
      prostate cancer revealed that reduced levels of this biomarker were a significant
      independent marker of poor clinical outcome. CONCLUSION: Here we report for the
      first time that a low DSG2 expression phenotype is a useful prognostic biomarker
      of tumor aggressiveness and may serve as an aid in identifying patients with
      clinically significant prostate cancer.

PMID- 24896106
TI  - Dynein regulation: going into circles can set things straight.

PMID- 24896107
TI  - Cardiac electrophysiology delivered a "grand slam" by angiotensin II: the third
      explanation of transmural cardiac electrical activity gradients.

PMID- 24896108
TI  - Vertex models of epithelial morphogenesis.
AB  - The dynamic behavior of epithelial cell sheets plays a central role during
      numerous developmental processes. Genetic and imaging studies of epithelial
      morphogenesis in a wide range of organisms have led to increasingly detailed
      mechanisms of cell sheet dynamics. Computational models offer a useful means by
      which to investigate and test these mechanisms, and have played a key role in the
      study of cell-cell interactions. A variety of modeling approaches can be used to
      simulate the balance of forces within an epithelial sheet. Vertex models are a
      class of such models that consider cells as individual objects, approximated by
      two-dimensional polygons representing cellular interfaces, in which each vertex
      moves in response to forces due to growth, interfacial tension, and pressure
      within each cell. Vertex models are used to study cellular processes within
      epithelia, including cell motility, adhesion, mitosis, and delamination. This
      review summarizes how vertex models have been used to provide insight into
      developmental processes and highlights current challenges in this area, including
      progressing these models from two to three dimensions and developing new tools
      for model validation. 

PMID- 24896111
TI  - Hyperglycemic and hyperlipidemic conditions alter cardiac cell biomechanical
      properties.
AB  - Currently, many diabetic cardiomyopathy (DC) studies focus on either in vitro
      molecular pathways or in vivo whole-heart properties such as ejection fraction.
      However, as DC is primarily a disease caused by changes in structural and
      functional properties, such studies may not precisely identify the influence of
      hyperglycemia or hyperlipidemia in producing specific cellular changes, such as
      increased myocardial stiffness or diastolic dysfunction. To address this need, we
      developed an in vitro approach to examine how structural and functional
      properties may change as a result of a diabetic environment. Particle-tracking
      microrheology was used to characterize the biomechanical properties of cardiac
      myocytes and fibroblasts under hyperglycemia or hyperlipidemic conditions. We
      showed that myocytes, but not fibroblasts, exhibited increased stiffness under
      diabetic conditions. Hyperlipidemia, but not hyperglycemia, led to increased cFos
      expression. Although direct application of reactive oxygen species had only
      limited effects that altered myocyte properties, the antioxidant N-acetylcysteine
      had broader effects in limiting glucose or fatty-acid alterations. Changes
      consistent with clinical DC alterations occur in cells cultured in elevated
      glucose or fatty acids. However, the individual roles of glucose, reactive oxygen
      species, and fatty acids are varied, suggesting multiple pathway involvement.

PMID- 24896109
TI  - Not just an oil slick: how the energetics of protein-membrane interactions
      impacts the function and organization of transmembrane proteins.
AB  - The membrane environment, its composition, dynamics, and remodeling, have been
      shown to participate in the function and organization of a wide variety of
      transmembrane (TM) proteins, making it necessary to study the molecular
      mechanisms of such proteins in the context of their membrane settings. We review
      some recent conceptual advances enabling such studies, and corresponding
      computational models and tools designed to facilitate the concerted experimental
      and computational investigation of protein-membrane interactions. To connect
      productively with the high resolution achieved by cognate experimental
      approaches, the computational methods must offer quantitative data at an
      atomistically detailed level. We show how such a quantitative method illuminated
      the mechanistic importance of a structural characteristic of multihelical TM
      proteins, that is, the likely presence of adjacent polar and hydrophobic residues
      at the protein-membrane interface. Such adjacency can preclude the complete
      alleviation of the well-known hydrophobic mismatch between TM proteins and the
      surrounding membrane, giving rise to an energy cost of residual hydrophobic
      mismatch. The energy cost and biophysical formulation of hydrophobic mismatch and
      residual hydrophobic mismatch are reviewed in the context of their mechanistic
      role in the function of prototypical members of multihelical TM protein families:
      1), LeuT, a bacterial homolog of mammalian neurotransmitter sodium symporters;
      and 2), rhodopsin and the beta1- and beta2-adrenergic receptors from the G
      protein coupled receptor family. The type of computational analysis provided by
      these examples is poised to translate the rapidly growing structural data for the
      many TM protein families that are of great importance to cell function into ever
      more incisive insights into mechanisms driven by protein-ligand and protein
      protein interactions in the membrane environment.

PMID- 24896112
TI  - Ultimate use of two-photon fluorescence microscopy to map orientational behavior
      of fluorophores.
AB  - The orientational distribution of fluorophores is an important reporter of the
      structure and function of their molecular environment. Although this distribution
      affects the fluorescence signal under polarized-light excitation, its retrieval
      is limited to a small number of parameters. Because of this limitation, the need
      for a geometrical model (cone, Gaussian, etc.) to effect such retrieval is often
      invoked. In this work, using a symmetry decomposition of the distribution
      function of the fluorescent molecules, we show that polarized two-photon
      fluorescence based on tunable linear dichroism allows for the retrieval of this
      distribution with reasonable fidelity and without invoking either an a priori
      knowledge of the system to be investigated or a geometrical model. We establish
      the optimal level of detail to which any distribution can be retrieved using this
      technique. As applied to artificial lipid vesicles and cell membranes, the
      ability of this method to identify and quantify specific structural properties
      that complement the more traditional molecular-order information is demonstrated.
      In particular, we analyze situations that give access to the sharpness of the
      angular constraint, and to the evidence of an isotropic population of
      fluorophores within the focal volume encompassing the membrane. Moreover, this
      technique has the potential to address complex situations such as the
      distribution of a tethered membrane protein label in an ordered environment. 

PMID- 24896110
TI  - How cells tune viral mechanics--insights from biophysical measurements of
      influenza virus.
AB  - During replication, the physical state of a virus is controlled by assembly and
      disassembly processes, when particles are put together and dismantled by cellular
      cues, respectively. A fundamental question has been how a cell can assemble an
      infectious virus, and dismantle a virus entering an uninfected cell and thereby
      trigger a new round of infection. This apparent paradox might be explained by
      considering that infected and uninfected cells are functionally different, or
      that assembly and disassembly take place along different cellular pathways. A
      third possibility is that the physical properties of newly assembled viruses are
      different from the infection-ready viruses. Recent biophysical experiments
      measured the stiffness of single Influenza viruses and combined this with
      biochemical measurements and cell biological assays. Besides inducing the
      fusogenic state of hemagglutinin, low pH cues softened the virus and precluded
      aggregation of viral ribonucleoprotein particles with the matrix protein M1. The
      recent experiments suggest a two-step model for Influenza virus entry and
      uncoating involving low pH in early and late endosomes, respectively. I conclude
      with a short outlook into how combined biophysical and cell biological approaches
      might lead to the identification of new cellular cues controlling viral uncoating
      and infection. 

PMID- 24896113
TI  - Dynamics of cell shape and forces on micropatterned substrates predicted by a
      cellular Potts model.
AB  - Micropatterned substrates are often used to standardize cell experiments and to
      quantitatively study the relation between cell shape and function. Moreover, they
      are increasingly used in combination with traction force microscopy on soft
      elastic substrates. To predict the dynamics and steady states of cell shape and
      forces without any a priori knowledge of how the cell will spread on a given
      micropattern, here we extend earlier formulations of the two-dimensional cellular
      Potts model. The third dimension is treated as an area reservoir for spreading.
      To account for local contour reinforcement by peripheral bundles, we augment the
      cellular Potts model by elements of the tension-elasticity model. We first
      parameterize our model and show that it accounts for momentum conservation. We
      then demonstrate that it is in good agreement with experimental data for shape,
      spreading dynamics, and traction force patterns of cells on micropatterned
      substrates. We finally predict shapes and forces for micropatterns that have not
      yet been experimentally studied. 

PMID- 24896114
TI  - Frequency and relative prevalence of calcium blips and puffs in a model of small
      IP3R clusters.
AB  - In this work, we model the local calcium release from clusters with a few
      inositol 1,4,5-trisphosphate receptor (IP3R) channels, focusing on the stochastic
      process in which an open channel either triggers other channels to open (as a
      puff) or fails to cause any channel to open (as a blip). We show that there are
      linear relations for the interevent interval (including blips and puffs) and the
      first event latency against the inverse cluster size. However, nonlinearity is
      found for the interpuff interval and the first puff latency against the inverse
      cluster size. Furthermore, the simulations indicate that the blip fraction among
      all release events and the blip frequency are increasing with larger basal
      [Ca(2+)], with blips in turn giving a growing contribution to basal [Ca(2+)].
      This result suggests that blips are not just lapses to trigger puffs, but they
      may also possess a biological function to contribute to the initiation of calcium
      waves by a preceding increase of basal [Ca(2+)] in cells that have small IP3R
      clusters.

PMID- 24896115
TI  - Autocrine A2 in the T-system of ventricular myocytes creates transmural gradients
      in ion transport: a mechanism to match contraction with load?
AB  - Transmural heterogeneities in Na/K pump current (IP), transient outward K(+)
      current (Ito), and Ca(2+)-current (ICaL) play an important role in regulating
      electrical and contractile activities in the ventricular myocardium. Prior
      studies indicated angiotensin II (A2) may determine the transmural gradient in
      Ito, but the effects of A2 on IP and ICaL were unknown. In this study, myocytes
      were isolated from five muscle layers between epicardium and endocardium. We
      found a monotonic gradient in both Ip and Ito, with the lowest currents in ENDO.
      When AT1Rs were inhibited, EPI currents were unaffected, but ENDO currents
      increased, suggesting endogenous extracellular A2 inhibits both currents in ENDO.
      IP- and Ito-inhibition by A2 yielded essentially the same K0.5 values, so they
      may both be regulated by the same mechanism. A2/AT1R-mediated inhibition of IP or
      Ito or stimulation of ICaL persisted for hours in isolated myocytes, suggesting
      continuous autocrine secretion of A2 into a restricted diffusion compartment,
      like the T-system. Detubulation brought EPI IP to its low ENDO value and
      eliminated A2 sensitivity, so the T-system lumen may indeed be the restricted
      diffusion compartment. These studies showed that 33-50% of IP, 57-65% of Ito, and
      a significant fraction of ICaL reside in T-tubule membranes where they are
      transmurally regulated by autocrine secretion of A2 into the T-system lumen and
      activation of AT1Rs. Increased AT1R activation regulates each of these currents
      in a direction expected to increase contractility. Endogenous A2 activation of
      AT1Rs increases monotonically from EPI to ENDO in a manner similar to reported
      increases in passive tension when the ventricular chamber fills with blood. We
      therefore hypothesize load is the signal that regulates A2-activation of AT1Rs,
      which create a contractile gradient that matches the gradient in load.

PMID- 24896116
TI  - Pore dynamics and conductance of RyR1 transmembrane domain.
AB  - Ryanodine receptors (RyR) are calcium release channels, playing a major role in
      the regulation of muscular contraction. Mutations in skeletal muscle RyR (RyR1)
      are associated with congenital diseases such as malignant hyperthermia and
      central core disease (CCD). The absence of high-resolution structures of RyR1 has
      limited our understanding of channel function and disease mechanisms at the
      molecular level. Previously, we have reported a hypothetical structure of the
      RyR1 pore-forming region, obtained by homology modeling and supported by
      mutational scans, electrophysiological measurements, and cryo-electron
      microscopy. Here, we utilize the expanded model encompassing six transmembrane
      helices to calculate the RyR1 pore region conductance, to analyze its structural
      stability, and to hypothesize the mechanism of the Ile4897 CCD-associated
      mutation. The calculated conductance of the wild-type RyR1 suggests that the
      proposed pore structure can sustain ion currents measured in single-channel
      experiments. We observe a stable pore structure on timescales of 0.2 MUs, with
      multiple cations occupying the selectivity filter and cytosolic vestibule, but
      not the inner chamber. We further suggest that stability of the selectivity
      filter critically depends on the interactions between the I4897 residue and
      several hydrophobic residues of the neighboring subunit. Loss of these
      interactions in the case of polar substitution I4897T results in destabilization
      of the selectivity filter, a possible cause of the CCD-specific reduced Ca(2+)
      conductance. 

PMID- 24896117
TI  - 3D hydrophobic moment vectors as a tool to characterize the surface polarity of
      amphiphilic peptides.
AB  - The interaction of membranes with peptides and proteins is largely determined by
      their amphiphilic character. Hydrophobic moments of helical segments are commonly
      derived from their two-dimensional helical wheel projections, and the same is
      true for beta-sheets. However, to the best of our knowledge, there exists no
      method to describe structures in three dimensions or molecules with irregular
      shape. Here, we define the hydrophobic moment of a molecule as a vector in three
      dimensions by evaluating the surface distribution of all hydrophilic and
      lipophilic regions over any given shape. The electrostatic potential on the
      molecular surface is calculated based on the atomic point charges. The resulting
      hydrophobic moment vector is specific for the instantaneous conformation, and it
      takes into account all structural characteristics of the molecule, e.g., partial
      unfolding, bending, and side-chain torsion angles. Extended all-atom molecular
      dynamics simulations are then used to calculate the equilibrium hydrophobic
      moments for two antimicrobial peptides, gramicidin S and PGLa, under different
      conditions. We show that their effective hydrophobic moment vectors reflect the
      distribution of polar and nonpolar patches on the molecular surface and the
      calculated electrostatic surface potential. A comparison of simulations in
      solution and in lipid membranes shows how the peptides undergo internal
      conformational rearrangement upon binding to the bilayer surface. A good
      correlation with solid-state NMR data indicates that the hydrophobic moment
      vector can be used to predict the membrane binding geometry of peptides. This
      method is available as a web application on http://www.ibg.kit.edu/HM/.

PMID- 24896118
TI  - Lipopolysaccharide-induced dynamic lipid membrane reorganization: tubules,
      perforations, and stacks.
AB  - Lipopolysaccharide (LPS) is a unique lipoglycan, with two major physiological
      roles: 1), as a major structural component of the outer membrane of Gram-negative
      bacteria and 2), as a highly potent mammalian toxin when released from cells into
      solution (endotoxin). LPS is an amphiphile that spontaneously inserts into the
      outer leaflet of lipid bilayers to bury its hydrophobic lipidic domain, leaving
      the hydrophilic polysaccharide chain exposed to the exterior polar solvent.
      Divalent cations have long been known to neutralize and stabilize LPS in the
      outer membrane, whereas LPS in the presence of monovalent cations forms highly
      mobile negatively-charged aggregates. Yet, much of our understanding of LPS and
      its interactions with the cell membrane does not take into account its
      amphiphilic biochemistry and charge polarization. Herein, we report fluorescence
      microscopy and atomic force microscopy analysis of the interaction between LPS
      and fluid-phase supported lipid bilayer assemblies (sLBAs), as model membranes.
      Depending on cation availability, LPS induces three remarkably different effects
      on simple sLBAs. Net-negative LPS-Na(+) leads to the formation of 100-MUm-long
      flexible lipid tubules from surface-associated lipid vesicles and the
      destabilization of the sLBA resulting in micron-size hole formation. Neutral LPS
      Ca(2+) gives rise to 100-MUm-wide single- or multilamellar planar sheets of lipid
      and LPS formed from surface-associated lipid vesicles. Our findings have
      important implications about the physical interactions between LPS and lipids and
      demonstrate that sLBAs can be useful platforms to study the interactions of
      amphiphilic virulence factors with cell membranes. Additionally, our study
      supports the general phenomenon that lipids with highly charged or bulky
      headgroups can promote highly curved membrane architectures due to electrostatic
      and/or steric repulsions.

PMID- 24896119
TI  - Structure prediction of the second extracellular loop in G-protein-coupled
      receptors.
AB  - G-protein-coupled receptors (GPCRs) play key roles in living organisms.
      Therefore, it is important to determine their functional structures. The second
      extracellular loop (ECL2) is a functionally important region of GPCRs, which
      poses significant challenge for computational structure prediction methods. In
      this work, we evaluated CABS, a well-established protein modeling tool for
      predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34
      residues) are predicted in an environment of other extracellular loops being
      fully flexible and the transmembrane domain fixed in its x-ray conformation. The
      modeling procedure used theoretical predictions of ECL2 secondary structure and
      experimental constraints on disulfide bridges. Our approach yielded ensembles of
      low-energy conformers and the most populated conformers that contained models
      close to the available x-ray structures. The level of similarity between the
      predicted models and x-ray structures is comparable to that of other state-of-the
      art computational methods. Our results extend other studies by including newly
      crystallized GPCRs.

PMID- 24896120
TI  - Direct visualization of the action of Triton X-100 on giant vesicles of
      erythrocyte membrane lipids.
AB  - The raft hypothesis proposes that microdomains enriched in sphingolipids,
      cholesterol, and specific proteins are transiently formed to accomplish important
      cellular tasks. Equivocally, detergent-resistant membranes were initially assumed
      to be identical to membrane rafts, because of similarities between their
      compositions. In fact, the impact of detergents in membrane organization is still
      controversial. Here, we use phase contrast and fluorescence microscopy to observe
      giant unilamellar vesicles (GUVs) made of erythrocyte membrane lipids (erythro
      GUVs) when exposed to the detergent Triton X-100 (TX-100). We clearly show that
      TX-100 has a restructuring action on biomembranes. Contact with TX-100 readily
      induces domain formation on the previously homogeneous membrane of erythro-GUVs
      at physiological and room temperatures. The shape and dynamics of the formed
      domains point to liquid-ordered/liquid-disordered (Lo/Ld) phase separation,
      typically found in raft-like ternary lipid mixtures. The Ld domains are then
      separated from the original vesicle and completely solubilized by TX-100. The
      insoluble vesicle left, in the Lo phase, represents around 2/3 of the original
      vesicle surface at room temperature and decreases to almost 1/2 at physiological
      temperature. This chain of events could be entirely reproduced with biomimetic
      GUVs of a simple ternary lipid mixture, 2:1:2 POPC/SM/chol
      (phosphatidylcholine/sphyngomyelin/cholesterol), showing that this behavior will
      arise because of fundamental physicochemical properties of simple lipid mixtures.
      This work provides direct visualization of TX-100-induced domain formation
      followed by selective (Ld phase) solubilization in a model system with a complex
      biological lipid composition.

PMID- 24896121
TI  - Microstructures in the organ of Corti help outer hair cells form traveling waves
      along the cochlear coil.
AB  - According to the generally accepted theory of mammalian cochlear mechanics, the
      fluid in the cochlear scalae interacts with the elastic cochlear partition to
      generate transversely oscillating displacement waves that propagate along the
      cochlear coil. Using a computational model of cochlear segments, a different type
      of propagating wave is reported, an elastic propagating wave that is independent
      of the fluid-structure interaction. The characteristics of the propagating wave
      observed in the model, such as the wavelength, speed, and phase lag, are similar
      to those observed in the living cochlea. Three conditions are required for the
      existence of the elastic propagating wave in the cochlear partition without fluid
      interaction: 1), the stiffness gradient of the cochlear partition; 2), the
      elastic longitudinal coupling; and 3), the Y-shaped structure in the organ of
      Corti formed by the outer hair cell, the Deiters cell, and the Deiters cell
      phalangeal process. The elastic propagating waves in the cochlear partition
      disappeared without the push-pull action provided by the outer hair cell and
      Deiters cell phalangeal process. The results suggest that the mechanical feedback
      of outer hair cells, facilitated by the organ of Corti microstructure, can
      control the tuning and amplification by modulating the cochlear traveling wave.

PMID- 24896122
TI  - Motor regulation results in distal forces that bend partially disintegrated
      Chlamydomonas axonemes into circular arcs.
AB  - The bending of cilia and flagella is driven by forces generated by dynein motor
      proteins. These forces slide adjacent microtubule doublets within the axoneme,
      the motile cytoskeletal structure. To create regular, oscillatory beating
      patterns, the activities of the axonemal dyneins must be coordinated both
      spatially and temporally. It is thought that coordination is mediated by stresses
      or strains, which build up within the moving axoneme, and somehow regulate dynein
      activity. During experimentation with axonemes subjected to mild proteolysis, we
      observed pairs of doublets associating with each other and forming bends with
      almost constant curvature. By modeling the statics of a pair of filaments, we
      show that the activity of the motors concentrates at the distal tips of the
      doublets. Furthermore, we show that this distribution of motor activity accords
      with models in which curvature, or curvature-induced normal forces, regulates the
      activity of the motors. These observations, together with our theoretical
      analysis, provide evidence that dynein activity can be regulated by curvature or
      normal forces, which may, therefore, play a role in coordinating the beating of
      cilia and flagella. 

PMID- 24896123
TI  - High-density 3D single molecular analysis based on compressed sensing.
AB  - Single molecule fitting-based superresolution microscopy achieves sub-diffraction
      limit image resolution but suffers from a need for long acquisition times to
      gather enough molecules. Several methods have recently been developed that
      analyze high molecule density images but most are only applicable to two
      dimensions. In this study, we implemented a high-density superresolution
      localization algorithm based on compressed sensing and a biplane approach that
      provides three-dimensional information about molecules, achieving super
      resolution imaging at higher molecule densities than those achieved using the
      conventional single molecule fitting method. 

PMID- 24896124
TI  - Nonequilibrium dissipation-free transport in F1-ATPase and the thermodynamic role
      of asymmetric allosterism.
AB  - F1-ATPase (or F1), the highly efficient and reversible biochemical engine, has
      motivated physicists as well as biologists to imagine the design principles
      governing machines in the fluctuating world. Recent experiments have clarified
      yet another interesting property of F1; the dissipative heat inside the motor is
      very small, irrespective of the velocity of rotation and energy transport.
      Conceptual interest is devoted to the fact that the amount of internal
      dissipation is not simply determined by the sequence of equilibrium pictures, but
      also relies on the rotational-angular dependence of nucleotide affinity, which is
      a truly nonequilibrium aspect. We propose that the totally asymmetric allosteric
      model (TASAM), where adenosine triphosphate (ATP) binding to F1 is assumed to
      have low dependence on the angle of the rotating shaft, produces results that are
      most consistent with the experiments. Theoretical analysis proves the crucial
      role of two time scales in the model, which explains the universal mechanism to
      produce the internal dissipation-free feature. The model reproduces the
      characteristic torque dependence of the rotational velocity of F1 and predicts
      that the internal dissipation upon the ATP synthesis direction rotation becomes
      large at the low nucleotide condition.

PMID- 24896125
TI  - Temperature changes in brown adipocytes detected with a bimaterial
      microcantilever.
AB  - Mammalian cells must produce heat to maintain body temperature and support other
      biological activities. Methods to measure a cell's thermogenic ability by
      inserting a thermometer into the cell or measuring the rate of oxygen consumption
      in a closed vessel can disturb its natural state. Here, we developed a
      noninvasive system for measuring a cell's heat production with a bimaterial
      microcantilever. This method is suitable for investigating the heat-generating
      properties of cells in their native state, because changes in cell temperature
      can be measured from the bending of the microcantilever, without damaging the
      cell and restricting its supply of dissolved oxygen. Thus, we were able to
      measure increases in cell temperature of <1 K in a small number of murine brown
      adipocytes (n = 4-7 cells) stimulated with norepinephrine, and observed a slow
      increase in temperature over several hours. This long-term heat production
      suggests that, in addition to converting fatty acids into heat energy, brown
      adipocytes may also adjust protein expression to raise their own temperature, to
      generate more heat. We expect this bimaterial microcantilever system to prove
      useful for determining a cell's state by measuring thermal characteristics.

PMID- 24896126
TI  - A statistical thermodynamic model for investigating the stability of DNA
      sequences from oligonucleotides to genomes.
AB  - We describe the development and testing of a simple statistical mechanics
      methodology for duplex DNA applicable to sequences of any composition and
      extensible to genomes. The microstates of a DNA sequence are modeled in terms of
      blocks of basepairs that are assumed to be fully closed (paired) or open. This
      approach generates an ensemble of bubblelike microstates that are used to
      calculate the corresponding partition function. The energies of the microstates
      are calculated as additive contributions from hydrogen bonding, basepair
      stacking, and solvation terms parameterized from a comprehensive series of
      molecular dynamics simulations including solvent and ions. Thermodynamic
      properties and nucleotide stability constants for DNA sequences follow directly
      from the partition function. The methodology was tested by comparing computed
      free energies per basepair with the experimental melting temperatures of 60
      oligonucleotides, yielding a correlation coefficient of -0.96. The thermodynamic
      stability of genic/nongenic regions was tested in terms of nucleotide stability
      constants versus sequence for the Escherichia coli K-12 genome. It showed clear
      differentiation of the genes from promoters and captures genic regions with a
      sensitivity of 0.94. The statistical thermodynamic model presented here provides
      a seemingly new handle on the challenging problem of interpreting genomic
      sequences.

PMID- 24896127
TI  - Probing the average local structure of biomolecules using small-angle scattering
      and scaling laws.
AB  - Small-angle neutron and x-ray scattering have become invaluable tools for probing
      the nanostructure of molecules in solution. It was recently shown that the
      definite integral of the scattering profile exhibits a scaling (power-law)
      behavior with respect to molecular mass. We derive the origin of this
      relationship, and discuss how the integrated scattering profile can be used to
      identify differing levels of disorder over local ?30 A length scales. We apply
      our analysis to globular and intrinsically disordered proteins.

PMID- 24896128
TI  - Differential mismatch recognition specificities of eukaryotic MutS homologs,
      MutSalpha and MutSbeta.
AB  - In eukaryotes, the recognition of the DNA postreplication errors and initiation
      of the mismatch repair is carried out by two MutS homologs: MutSalpha and
      MutSbeta. MutSalpha recognizes base mismatches and 1 to 2 unpaired nucleotides
      whereas MutSbeta recognizes longer insertion-deletion loops (IDLs) with 1 to 15
      unpaired nucleotides as well as certain mismatches. Results from molecular
      dynamics simulations of native MutSbeta:IDL-containing DNA and MutSalpha:mismatch
      DNA complexes as well as complexes with swapped DNA substrates provide
      mechanistic insight into how the differential substrate specificities are
      achieved by MutSalpha and MutSbeta, respectively. Our simulations results suggest
      more extensive interactions between MutSbeta and IDL-DNA and between MutSalpha
      and mismatch-containing DNA that suggest corresponding differences in stability.
      Furthermore, our simulations suggest more expanded mechanistic details involving
      a different degree of bending when DNA is bound to either MutSalpha or MutSbeta
      and a more likely opening of the clamp domains when noncognate substrates are
      bound. The simulation results also provide detailed information on key residues
      in MutSbeta and MutSalpha that are likely involved in recognizing IDL-DNA and
      mismatch-containing DNA, respectively.

PMID- 24896129
TI  - E. coli outer membrane and interactions with OmpLA.
AB  - The outer membrane of Gram-negative bacteria is a unique asymmetric lipid bilayer
      composed of phospholipids (PLs) in the inner leaflet and lipopolysaccharides
      (LPSs) in the outer leaflet. Its function as a selective barrier is crucial for
      the survival of bacteria in many distinct environments, and it also renders Gram
      negative bacteria more resistant to antibiotics than their Gram-positive
      counterparts. Here, we report the structural properties of a model of the
      Escherichia coli outer membrane and its interaction with outer membrane
      phospholipase A (OmpLA) utilizing molecular dynamics simulations. Our results
      reveal that given the lipid composition used here, the hydrophobic thickness of
      the outer membrane is ~3 A thinner than the corresponding PL bilayer, mainly
      because of the thinner LPS leaflet. Further thinning in the vicinity of OmpLA is
      observed due to hydrophobic matching. The particular shape of the OmpLA barrel
      induces various interactions between LPS and PL leaflets, resulting in asymmetric
      thinning around the protein. The interaction between OmpLA extracellular loops
      and LPS (headgroups and core oligosaccharides) stabilizes the loop conformation
      with reduced dynamics, which leads to secondary structure variation and loop
      displacement compared to that in a DLPC bilayer. In addition, we demonstrate that
      the LPS/PL ratios in asymmetric bilayers can be reliably estimated by the per
      lipid surface area of each lipid type, and there is no statistical difference in
      the overall membrane structure for the outer membranes with one more or less LPS
      in the outer leaflet, although individual lipid properties vary slightly.

PMID- 24896130
TI  - Light harvesting by lamellar chromatophores in Rhodospirillum photometricum.
AB  - Purple photosynthetic bacteria harvest light using pigment-protein complexes
      which are often arranged in pseudo-organelles called chromatophores. A model of a
      chromatophore from Rhodospirillum photometricum was constructed based on atomic
      force microscopy data. Molecular-dynamics simulations and quantum-dynamics
      calculations were performed to characterize the intercomplex excitation transfer
      network and explore the interplay between close-packing and light-harvesting
      efficiency.

PMID- 24896131
TI  - Rate-dependent behavior of the amorphous phase of spider dragline silk.
AB  - The time-dependent stress-strain behavior of spider dragline silk was already
      observed decades ago, and has been attributed to the disordered sequences in silk
      proteins, which compose the soft amorphous matrix. However, the actual molecular
      origin and magnitude of internal friction within the amorphous matrix has
      remained inaccessible, because experimentally decomposing the mechanical response
      of the amorphous matrix from the embedded crystalline units is challenging. Here,
      we used atomistic molecular dynamics simulations to obtain friction forces for
      the relative sliding of peptide chains of Araneus diadematus spider silk within
      bundles of these chains as a representative unit of the amorphous matrix in silk
      fibers. We computed the friction coefficient and coefficient of viscosity of the
      amorphous phase to be in the order of 10(-6) Ns/m and 10(4) Ns/m(2),
      respectively, by extrapolating our simulation data to the viscous limit. Finally,
      we used a finite element method for the amorphous phase, solely based on
      parameters derived from molecular dynamics simulations including the newly
      determined coefficient of viscosity. With this model the time scales of stress
      relaxation, creep, and hysteresis were assessed, and found to be in line with the
      macroscopic time-dependent response of silk fibers. Our results suggest the
      amorphous phase to be the primary source of viscosity in silk and open up the
      avenue for finite element method studies of silk fiber mechanics including
      viscous effects. 

PMID- 24896132
TI  - The local forces acting on the mechanotransduction channel in hair cell
      stereocilia.
AB  - In hair cells, mechanotransduction channels are located in the membrane of
      stereocilia tips, where the base of the tip link is attached. The tip-link force
      determines the system of other forces in the immediate channel environment, which
      change the channel open probability. This system of forces includes components
      that are out of plane and in plane relative to the membrane; the magnitude and
      direction of these components depend on the channel environment and arrangement.
      Using a computational model, we obtained the major forces involved as functions
      of the force applied via the tip link at the center of the membrane. We simulated
      factors related to channels and the membrane, including finite-sized channels
      located centrally or acentrally, stiffness of the hypothesized channel
      cytoskeleton tether, and bending modulus of the membrane. Membrane forces are
      perpendicular to the directions of the principal curvatures of the deformed
      membrane. Our approach allows for a fine vectorial picture of the local forces
      gating the channel; membrane forces change with the membrane curvature and are
      themselves sufficient to affect the open probability of the channel. 

PMID- 24896134
TI  - Comment on "anomalous versus slowed-down Brownian diffusion in the ligand-binding
      equilibrium".

PMID- 24896133
TI  - Platelet dynamics in three-dimensional simulation of whole blood.
AB  - A high-fidelity computational model using a 3D immersed boundary method is used
      to study platelet dynamics in whole blood. We focus on the 3D effects of the
      platelet-red blood cell (RBC) interaction on platelet margination and near-wall
      dynamics in a shear flow. We find that the RBC distribution in whole blood
      becomes naturally anisotropic and creates local clusters and cavities. A platelet
      can enter a cavity and use it as an express lane for a fast margination toward
      the wall. Once near the wall, the 3D nature of the platelet-RBC interaction
      results in a significant platelet movement in the transverse (vorticity)
      direction and leads to anisotropic platelet diffusion within the RBC-depleted
      zone or cell-free layer (CFL). We find that the anisotropy in platelet motion
      further leads to the formation of platelet clusters, even in the absence of any
      platelet-platelet adhesion. The transverse motion, and the size and number of the
      platelet clusters are observed to increase with decreasing CFL thickness. The 3D
      nature of the platelet-RBC collision also induces fluctuations in off-shear plane
      orientation and, hence, a rotational diffusion of the platelets. Although most
      marginated platelets are observed to tumble just outside the RBC-rich zone,
      platelets further inside the CFL are observed to flow with an intermittent
      dynamics that alters between sliding and tumbling, as a result of the off-shear
      plane rotational diffusion, bringing them even closer to the wall. To our
      knowledge, these new findings are based on the fundamentally 3D nature of the
      platelet-RBC interaction, and they underscore the importance of using cellular
      scale 3D models of whole blood to understand platelet margination and near-wall
      platelet dynamics. 

PMID- 24896135
TI  - Reply to the comment by V. P. Shkilev on "anomalous versus slowed-down Brownian
      diffusion in the ligand-binding equilibrium".

PMID- 24896136
TI  - Changes in retinal blood flow in patients with macular edema secondary to branch
      retinal vein occlusion before and after intravitreal injection of bevacizumab.
AB  - PURPOSE: To investigate the effect of intravitreal bevacizumab (IVB) injections
      for macular edema secondary to acute branch retinal vein occlusion on the retinal
      microcirculation. METHODS: The study was a prospective, interventional case
      series. Central macular thickness using spectral-domain optical coherence
      tomography and retinal blood flow (RBF) in untreated eyes with macular edema
      secondary to acute branch retinal vein occlusion in occluded (V1) and opposite
      venules in affected eyes (V2) and the equivalent venules in contralateral eyes
      (V3), using laser Doppler velocimetry during follow-up and after IVB injection,
      were measured. RESULTS: In 33 eyes with acute branch retinal vein occlusion of <2
      months of duration at the first visit, changes in the retinal microcirculation
      for 1 month was observed; the macular edema improved spontaneously, and the RBF
      was unchanged in 15 of 33 eyes, and the RBF increased by 23.3% in 18 eyes with
      persistent macular edema. Twenty-four eyes received an IVB injection (1.25 mg per
      0.05 mL). The RBF did not change significantly during follow-up. In 8 of 24 eyes
      (33%) with improved macular edema 3 months after the treatment, the average RBF
      values before injection were significantly higher compared with that of eyes with
      recurrent edema. CONCLUSION: One IVB injection might have little effect on the
      retinal microcirculation in patients with macular edema secondary to acute branch
      retinal vein occlusion at least 3 months after the injection. However, the
      increased RBF in the occluded venules before injection might be associated with
      improved macular edema after the IVB injection.

PMID- 24896137
TI  - Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects
      with neovascular age-related macular degeneration.
AB  - PURPOSE: To evaluate pazopanib 10 mg/mL eye drops (pazopanib) in healthy subjects
      and in subjects with previously untreated subfoveal choroidal neovascularization
      secondary to age-related macular degeneration. METHODS: Study 1 (single center,
      randomized, placebo-controlled, double-masked) included 3 cohorts of 12 to 13
      healthy subjects each who instilled pazopanib or placebo 4 times daily for 2
      weeks. Study 2 (multicenter open-label) included 19 subjects with neovascular age
      related macular degeneration who instilled pazopanib 4 times daily for 12 weeks.
      Both studies evaluated pharmacokinetics and safety. Study 2 also evaluated
      efficacy. RESULTS: Steady-state concentrations of pazopanib in plasma seemed to
      be reached by Week 2. At Week 4 (Study 2), there were no meaningful changes from
      baseline in the mean central retinal thickness (37.9 MUm) or best-corrected
      visual acuity (0.1 letters) (primary endpoint), retinal morphology, choroidal
      neovascularization size, or total lesion size. Complement Factor H genotype had
      no effect on changes from baseline in the best-corrected visual acuity or central
      retinal thickness. The most common pazopanib-related ocular adverse events
      included eye irritation (Study 1, n = 7) and instillation site pain (Study 2, n =
      3). No serious adverse events were reported. CONCLUSION: Pazopanib was well
      tolerated. In subjects with previously untreated neovascular age-related macular
      degeneration, pazopanib instilled 4 times daily as monothereapy did not seem to
      improve the best-corrected visual acuity or decrease the central retinal
      thickness.

PMID- 24896138
TI  - Choroidal thickness in macular telangiectasia type 2.
AB  - PURPOSE: To assess the choroidal thickness changes in eyes with macular
      telangiectasia Type 2 and their relationship with the integrity of outer retinal
      structures and visual acuity. METHODS: This is a prospective observational study
      that included 81 eyes (41 subjects) with macular telangiectasia Type 2, including
      21 women who underwent enhanced depth choroidal imaging. The choroidal thickness
      measurements were made at the fovea and at 5 points with an interval of 500 MUm
      in both directions, nasal and temporal from the fovea, and were compared with age
      matched healthy subjects. Masked observers assessed the outer retinal structure
      integrity. Stepwise regression was used to find the relationship between age,
      spherical equivalent, central macular thickness, integrity of the inner
      segment/outer segment junction, external limiting membrane integrity, and
      subfoveal choroidal thickness (SFCT). RESULTS: The mean age of the subjects was
      55.2 +/- 7.8 years in study subjects. The mean SFCT was 274.6 +/- 45.7 MUm. There
      was no significant difference between the SFCT in eyes with macular
      telangiectasia Type 2 and age-matched healthy subjects (P = 0.38). There was no
      correlation between the visual acuity (r = 0.008); integrity of inner
      segment/outer segment (r = 0.54); external limiting membrane (r = 0.47); central
      macular thickness (r = 0.31) and SFCT. CONCLUSION: Choroidal thickness did not
      vary between eyes with macular telangiectasia Type 2 and age-matched healthy
      subjects. There was no correlation between SFCT and visual acuity, and integrity
      of the outer retinal structures and central macular thickness.

PMID- 24896139
TI  - Pregnancy outcomes in Marfan syndrome: a retrospective cohort study.
AB  - OBJECTIVE: Marfan syndrome (MFS) is a rare connective tissue disease with
      significant risk for adverse cardiovascular outcomes. Our objective was to
      evaluate pregnancy and cardiovascular outcomes in pregnant women with MFS. STUDY
      DESIGN: We conducted a population-based retrospective cohort study using the
      Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP NIS)
      database from 2003 to 2010. We used unconditional regression analyses to compare
      maternal and fetal outcomes among pregnancies in women with and without MFS.
      RESULTS: Out of the 7,094,400 births in our cohort, 339 deliveries were to women
      with MFS. There was one maternal death and six aortic dissections among women
      with MFS. Births to women with MFS were more likely to be premature, odds ratio
      (OR) 2.15 (1.60-2.89), have intrauterine growth restricted and small for
      gestational age infants, OR 2.06 (1.24-3.43). Women with MFS were more likely to
      deliver by cesarean section, OR 1.91 (1.53-2.38) and were at higher risk of major
      morbidities including cardiac arrhythmias, OR 10.64 (5.49-20.61) and
      pneumothorax, OR 51.95 (6.18, 437.10). CONCLUSION: Pregnant women with MFS are at
      a particularly high risk of adverse pregnancy and cardiovascular events.
      Preconception counseling should take these risks into consideration and
      appropriate pregnancy care in tertiary centers should be considered.

PMID- 24896140
TI  - Perceptions of webcams in the neonatal intensive care unit: here's looking at you
      kid!
AB  - INTRODUCTION: Many tertiary neonatal units employ a restricted visiting policy.
      Webcams have previously been implemented in the neonatal unit setting in several
      countries. OBJECTIVES: This study aims to determine the views from parents,
      physicians, and nursing staff before implementation of a webcam system. METHODS:
      A questionnaire-based study. RESULTS: There were 101 responses. Parental computer
      usage was 83%. The majority of parents indicated that they would use the webcam
      system. Parents felt that a webcam system would reduce stress. Members of the
      nursing staff were most concerned about privacy risks (68%), compared with
      parents who were confident in the security of these systems (92%, p-value <
      0.001). Seventy two percent of nurses felt that a webcam system would increase
      the stress levels of staff as compared with less than 20% of the physicians (p
      value < 0.001). DISCUSSION: The majority of parents who completed the
      questionnaire have positive attitudes toward implementation of a webcam system in
      the NICU. Education of health care staff is required before implementation.

PMID- 24896141
TI  - A pilot randomized, controlled trial of metformin versus insulin in women with
      type 2 diabetes mellitus during pregnancy.
AB  - OBJECTIVE: Few studies support oral diabetic treatment in pregnant women with
      type 2 diabetes mellitus (T2DM). The objective of this study was to compare the
      effects of metformin versus insulin on achieving glycemic control and improving
      maternal and neonatal outcomes in pregnant women with T2DM. STUDY DESIGN: A pilot
      randomized, controlled trial was conducted of metformin versus insulin for the
      treatment of T2DM during pregnancy. The primary outcome was glycemic control
      measured with hemoglobin A1c < 7% at delivery. Maternal and neonatal outcomes
      were compared between groups. RESULTS: In this study, 8 women received metformin
      and 11 received insulin. All women in both groups achieved glycemic control by
      delivery (HgbA1c: metformin 5.96 +/- 5.88 vs. insulin 6.34 +/- 0.92%). There were
      similar rates of cesarean delivery, birth weights, neonatal intensive care unit
      admissions, respiratory distress syndrome, and neonatal dextrose treatment
      between groups. There was one case of fetal macrosomia in the insulin group, one
      case of shoulder dystocia in the metformin group and no cases of failed metformin
      therapy. CONCLUSION: In this pilot study, glycemic control was achieved in women
      who received metformin and insulin. Larger studies are needed to determine
      whether metformin can be considered a reasonable alternative to insulin in
      pregnant women with T2DM.

PMID- 24896142
TI  - New definitions of 6 clinical signs of perceptual disorder in children with
      cerebral palsy: an observational study through reliability measures.
AB  - BACKGROUND: Recently authors have begun to emphasize the non-motor aspects of
      Cerebral Palsy and their influence on motor control and recovery prognosis. Much
      has been written about single clinical signs (i.e., startle reaction) but so far
      no definitions of the six perceptual signs presented in this study have appeared
      in literature. AIM: This study defines 6 signs (startle reaction, upper limbs in
      startle position, frequent eye blinking, posture freezing, averted eye gaze,
      grimacing) suggestive of perceptual disorders in children with cerebral palsy and
      measures agreement on sign recognition among independent observers and
      consistency of opinions over time. DESIGN: Observational study with both cross
      sectional and prospective components. SETTING: Fifty-six videos presented to
      observers in random order. Videos were taken from 19 children with a bilateral
      form of cerebral palsy referred to the Children Rehabilitation Unit in Reggio
      Emilia. PARTICIPANTS: Thirty-five rehabilitation professionals from all over
      Italy: 9 doctors and 26 physiotherapists. METHODS: Measure of agreement among 35
      independent observers was compiled from a sample of 56 videos. Interobserver
      reliability was determined using the K index of Fleiss and reliability intra
      observer was calculated by the Spearman correlation index between ranks (rho -
      rho). Percentage of agreement between observers and Gold Standard was used as
      criterion validity. RESULTS: Interobserver reliability was moderate for startle
      reaction, upper limb in startle position, adverted eye gaze and eye-blinking and
      fair for posture freezing and grimacing. Intraobserver reliability remained
      consistent over time. Criterion validity revealed very high agreement between
      independent observer evaluation and gold standard. CONCLUSIONS: Semiotics of
      perceptual disorders can be used as a specific and sensitive instrument in order
      to identify a new class of patients within existing heterogeneous clinical types
      of bilateral cerebral palsy forms and could help clinicians in identifying
      functional prognosis. CLINICAL REHABILITATION IMPACT: To provide clinicians with
      a definition of 6 clinical signs found in children with cerebral palsy in routine
      rehabilitation settings. Future research should explore the link between these
      signs and motor prognosis (i.e., time to independent walking).

PMID- 24896143
TI  - Predictors of outcome following a short multimodal rehabilitation program for
      patients with whiplash associated disorders.
AB  - BACKGROUND: Patients with whiplash associated disorders (WAD) may present with
      physical and psychological symptoms which persist long after the initial onset of
      pain. Several studies have shown that therapeutic exercise for motor and
      sensorimotor control combined with manual therapy in a multimodal rehabilitation
      (MMR) program is effective at improving pain and disability in patients with neck
      disorders. To date, no studies have investigated which self-reported physical or
      psychological symptoms are predictive of response to this MMR program. AIM: To
      determine which baseline features can predict outcome following a 3-week MMR
      program in patients with WAD. DESIGN: Observational prospective cohort study.
      SETTING: Outpatient rehabilitation clinic. POPULATION: Thirty-seven patients aged
      >18 years with a diagnosis of WAD grade II or III. METHODS: The MMR program
      included manual therapy, motor control and sensorimotor control training
      according to the clinical impairments of each patient. Patients were assessed
      before and after treatment for their physical and psychological symptoms by means
      of self-reported questionnaires. Regression models were estimated with pain
      intensity, disability and post-traumatic stress symptoms (PTSS) as outcomes.
      RESULTS: After treatment, patients exhibited significant improvements in all
      evaluated outcomes (all P<0.01). Regression models accounting for 35% and 36% of
      the variance in pain intensity outcomes included average pain intensity over the
      previous week and pain catastrophizing as significant predictors. Disability and
      pain catastrophizing were predictors of changes in disability following the MMR
      program explaining 49% of the variance in the model. Furthermore, higher PTSS at
      baseline was a significant predictor of PTSS after treatment, explaining 55% of
      the variance in the model. CONCLUSION: Improved outcomes on pain intensity,
      disability and PTSS following a MMR program could be partially predicted based on
      the patient's initial presentation. CLINICAL REHABILITATION IMPACT: This
      knowledge may assist clinicians in predicting outcome following a MMR program
      inclusive of specific exercise therapy and manual therapy in patients with WAD.

PMID- 24896144
TI  - Aligning private sector incentives with health care quality: need for quality
      adjusted hospital bond ratings.

PMID- 24896145
TI  - Advancing quality measurement to include the patient perspective.

PMID- 24896146
TI  - Comprehensive massive parallel DNA sequencing strategy for the genetic diagnosis
      of the neuro-cardio-facio-cutaneous syndromes.
AB  - Variants in 11 genes of the RAS/MAPK signaling pathway have been causally linked
      to the neuro-cardio-facio-cutaneous syndromes group (NCFCS). Recently, A2ML1 and
      RIT1 were also associated with these syndromes. Because of the genetic and
      clinical heterogeneity of NCFCS, it is challenging to define strategies for their
      molecular diagnosis. The aim of this study was to develop and validate a massive
      parallel sequencing (MPS)-based strategy for the molecular diagnosis of NCFCS. A
      multiplex PCR-based strategy for the enrichment of the 13 genes and a variant
      prioritization pipeline was established. Two sets of genomic DNA samples were
      studied using the Ion PGM System: (1) training set (n =15) to optimize the
      strategy and (2) validation set (n = 20) to validate and evaluate the power of
      the new methodology. Sanger sequencing was performed to confirm all variants and
      low covered regions. All variants identified by Sanger sequencing were detected
      with our MPS approach. The methodology resulted in an experimental approach with
      a specificity of 99.0% and a maximum analytical sensitivity of >= 98.2% with a
      confidence of 99%. Importantly, two patients (out of 20) harbored described
      disease-causing variants in genes that are not routinely tested (RIT1 and SHOC2).
      The addition of less frequently altered genes increased in ~ 10% the diagnostic
      yield of the strategy currently used. The presented workflow provides a
      comprehensive genetic screening strategy for patients with NCFCS in a fast and
      cost-efficient manner. This approach demonstrates the potential of a combined MPS
      Sanger sequencing-based strategy as an effective diagnostic tool for
      heterogeneous diseases.

PMID- 24896147
TI  - Role of TNF block genetic variants in HIV-associated sensory neuropathy in black
      Southern Africans.
AB  - HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication
      of HIV infection. The TNF block is a region within the central MHC that contains
      many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have
      been associated with increased risk of HIV-SN in Asians and whites. Here we
      investigated genetic associations with HIV-SN in 342 black Southern Africans (190
      cases and 152 neuropathy-free controls) using single nucleotide polymorphisms
      (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian
      and white populations (denoted FVa). We included population-appropriate tagSNPs
      derived from an African population (Yoruban, YRI, HapMap) and derived extended
      haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association
      between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1
      (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians.
      Additionally, a haplotype containing TNF-1031/rs1799964*C associated with
      increased risk of HIV-SN in Asians, but was not present in this African
      population. However, alleles of seven SNPs associated with reduced risk of HIV-SN
      (corrected for age, height and multiple comparisons). These were rs11796*A,
      rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A,
      LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these
      alleles, was associated with increased risk of HIV-SN after correction for age,
      height and multiple comparisons. Our results confirm the involvement of genes in
      the TNF block in altering risk for HIV-SN, but genotypes critical in this African
      population differed from those affecting HIV-SN in whites and Asians. These
      differences support the need for genetic association studies in diverse
      populations. 

PMID- 24896148
TI  - The functional polymorphism rs73598374:G>A (p.Asp8Asn) of the ADA gene is
      associated with telomerase activity and leukocyte telomere length.
AB  - Recent evidence demonstrated a relevant role of adenosine deaminase (ADA) in
      replicative senescence of T cells through its capacity to modulate telomerase
      activity (TA). Herein, we tested the impact of the functional polymorphism ADA
      rs73598374:G>A (c.22G>A, p.Asp8Asn) on telomere biology, by measuring TA and
      leukocyte telomere length (LTL) in healthy subjects selected according to
      rs73598374 genotype. rs73598374-A carriers showed lower TA (P=0.019) and shorter
      LTL (P=0.003), respectively, compared to G/G carriers. rs73598374-A carriers
      showed a stronger cross-sectional age reduction of LTL (r=-0.314, P=0.005)
      compared to G/G carriers (r=-0.243, P=0.022). The reduced ADA activity associated
      to rs73598374-A variant predisposes those carriers to display higher levels of
      adenosine compared to G/G carriers. Consequently, it may lead to an accelerated
      process of replicative senescence, causing a stronger reduction of TA and in turn
      shorter LTL. In conclusion, the crucial role played by replicative senescence of
      the immune system in several human diseases and in the aging process underscores
      the relevance of the present findings and also spurs interest into the possible
      involvement of rs73598374 in shaping the susceptibility to several age-related
      diseases. 

PMID- 24896150
TI  - Genome-wide haplotypic testing in a Finnish cohort identifies a novel association
      with low-density lipoprotein cholesterol.
AB  - We performed genome-wide tests for association between haplotype clusters and
      each of 9 metabolic traits in a cohort of 5402 Northern Finnish individuals
      genotyped for 330 000 single-nucleotide polymorphisms. The metabolic traits were
      body mass index, C-reactive protein, diastolic blood pressure, glucose, high
      density lipoprotein (HDL), insulin, low-density lipoprotein (LDL), systolic blood
      pressure, and triglycerides. Haplotype clusters were determined using Beagle.
      There were LDL-associated clusters in the chromosome 4q13.3-q21.1 region
      containing the albumin (ALB) and platelet factor 4 (PF4) genes. This region has
      not been associated with LDL in previous genome-wide association studies. The
      most significant haplotype cluster in this region was associated with 0.488
      mmol/l higher LDL (95% CI: 0.361-0.615 mmol/l, P-value: 6.4 * 10(-14)). We also
      observed three previously reported associations: Chromosome 16q13 with HDL,
      chromosome 1p32.3-p32.2 with LDL and chromosome 19q13.31-q13.32 with LDL. The
      chromosome 1 and chromosome 4 LDL associations do not reach genome-wide
      significance in single-marker analyses of these data, illustrating the power of
      haplotypic association testing. 

PMID- 24896151
TI  - Clinical utility gene card for: Angelman Syndrome.

PMID- 24896152
TI  - Improved phylogenetic resolution and rapid diversification of Y-chromosome
      haplogroup K-M526 in Southeast Asia.
AB  - The highly structured distribution of Y-chromosome haplogroups suggests that
      current patterns of variation may be informative of past population processes.
      However, limited phylogenetic resolution, particularly of subclades within
      haplogroup K, has obscured the relationships of lineages that are common across
      Eurasia. Here we genotype 13 new highly informative single-nucleotide
      polymorphisms in a worldwide sample of 4413 males that carry the derived allele
      at M526, and reconstruct an NRY haplogroup tree with significantly higher
      resolution for the major clade within haplogroup K, K-M526. Although K-M526 was
      previously characterized by a single polytomy of eight major branches, the
      phylogenetic structure of haplogroup K-M526 is now resolved into four major
      subclades (K2a-d). The largest of these subclades, K2b, is divided into two
      clusters: K2b1 and K2b2. K2b1 combines the previously known haplogroups M, S, K
      P60 and K-P79, whereas K2b2 comprises haplogroups P and its subhaplogroups Q and
      R. Interestingly, the monophyletic group formed by haplogroups R and Q, which
      make up the majority of paternal lineages in Europe, Central Asia and the
      Americas, represents the only subclade with K2b that is not geographically
      restricted to Southeast Asia and Oceania. Estimates of the interval times for the
      branching events between M9 and P295 point to an initial rapid diversification
      process of K-M526 that likely occurred in Southeast Asia, with subsequent
      westward expansions of the ancestors of haplogroups R and Q. 

PMID- 24896149
TI  - Improved imputation quality of low-frequency and rare variants in European
      samples using the 'Genome of The Netherlands'.
AB  - Although genome-wide association studies (GWAS) have identified many common
      variants associated with complex traits, low-frequency and rare variants have not
      been interrogated in a comprehensive manner. Imputation from dense reference
      panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped
      variants for association. Here we present the results of imputation using a
      large, new population-specific panel: the Genome of The Netherlands (GoNL). We
      benchmarked the performance of the 1000G and GoNL reference sets by comparing
      imputation genotypes with 'true' genotypes typed on ImmunoChip in three European
      populations (Dutch, British, and Italian). GoNL showed significant improvement in
      the imputation quality for rare variants (MAF 0.05-0.5%) compared with 1000G. In
      Dutch samples, the mean observed Pearson correlation, r(2), increased from 0.61
      to 0.71. We also saw improved imputation accuracy for other European populations
      (in the British samples, r(2) improved from 0.58 to 0.65, and in the Italians
      from 0.43 to 0.47). A combined reference set comprising 1000G and GoNL improved
      the imputation of rare variants even further. The Italian samples benefitted the
      most from this combined reference (the mean r(2) increased from 0.47 to 0.50). We
      conclude that the creation of a large population-specific reference is
      advantageous for imputing rare variants and that a combined reference panel
      across multiple populations yields the best imputation results. 

PMID- 24896153
TI  - Use of stereotypical mutational motifs to define resolution limits for the ultra
      deep resequencing of mitochondrial DNA.
AB  - Massively parallel resequencing of mitochondrial DNA (mtDNA) has led to
      significant advances in the study of heteroplasmic mtDNA variants in health and
      disease, but confident resolution of very low-level variants (<2% heteroplasmy)
      remains challenging due to the difficulty in distinguishing signal from noise at
      this depth. However, it is likely that such variants are precisely those of
      greatest interest in the study of somatic (acquired) mtDNA mutations. Previous
      approaches to this issue have included the use of controls such as phage DNA and
      mtDNA clones, both of which may not accurately recapitulate natural mtDNA. We
      have therefore explored a novel approach, taking advantage of mtDNA with a known
      stereotyped mutational motif (nAT > C, from patient with MNGIE, mitochondrial
      neurogastrointestinal encephalomyopathy) and comparing mutational pattern
      distribution with healthy mtDNA by ligation-mediated deep resequencing (Applied
      Biosystems SOLiD). We empirically derived mtDNA-mutant heteroplasmy detection
      limits, demonstrating that the presence of stereotypical mutational motif could
      be statistically validated for heteroplasmy thresholds >= 0.22% (P = 0.034). We
      therefore provide empirical evidence from biological samples that very low-level
      mtDNA mutants can be meaningfully resolved by massively parallel resequencing,
      confirming the utility of the approach for studying somatic mtDNA mutation in
      health and disease. Our approach could also usefully be employed in other
      settings to derive platform-specific deep resequencing resolution limits.

PMID- 24896154
TI  - Validity and reliability of the look Keo power pedal system for measuring power
      output during incremental and repeated sprint cycling.
AB  - Power meters have traditionally been integrated into the crank set, but several
      manufacturers have designed new systems located elsewhere on the bike, such as
      inside the pedals. PURPOSE: This study aimed to determine the validity and
      reliability of the Keo power pedals during several laboratory cycling tasks.
      METHODS: Ten active male participants (mean +/- SD age 34.0 +/- 10.6 y, height
      1.77 +/- 0.04 m, body mass 76.5 +/- 10.7 kg) familiar with laboratory cycling
      protocols completed this study. Each participant was required to complete 2
      laboratory cycling trials on an SRM ergometer (SRM, Germany) that was also fitted
      with the Keo power pedals (Look, France). The trials consisted of an incremental
      test to exhaustion followed by 10 min rest and then three 10-s sprint tests
      separated by 3 min of cycling at 100 W. RESULTS: Over power ranges of 75 to 1147
      W, the Keo power-pedal system produced typical error values of 0.40, 0.21, and
      0.21 for the incremental, sprint, and combined trials, respectively, compared
      with the SRM. Mean differences of 21.0 and 18.6 W were observed between trials 1
      and 2 with the Keo system in the incremental and combined protocols,
      respectively. In contrast, the SRM produced differences of 1.3 and 0.6 W for the
      same protocols. CONCLUSIONS: The power data from the Keo power pedals should be
      treated with some caution given the presence of mean differences between them and
      the SRM. Furthermore, this is exacerbated by poorer reliability than that of the
      SRM power meter.

PMID- 24896155
TI  - Evolution and characteristics of GaN nanowires produced via maskless reactive ion
      etching.
AB  - The formation of nanowires (NWs) by reactive ion etching (RIE) of maskless GaN
      layers was investigated. The morphological, structural and optical
      characteristics of the NWs were studied and compared to those of the layer they
      evolve from. It is shown that the NWs are the result of a defect selective
      etching process. The evolution of density and length with etching time is
      discussed. Densely packed NWs with a length of more than 1 MUm and a diameter of
      ~60 nm were obtained by RIE of a ~2.5 MUm thick GaN layer. The NWs are
      predominantly free of threading dislocations and show an improvement of optical
      properties compared to their layer counterpart. The production of NWs via a top
      down process on non-masked group III-nitride layers is assessed to be very
      promising for photovoltaic applications. 

PMID- 24896156
TI  - EuroSCORE II and the importance of a local model, InsCor and the future SP-SCORE.
AB  - INTRODUCTION: The most widely used model for predicting mortality in cardiac
      surgery was recently remodeled, but the doubts regarding its methodology and
      development have been reported. OBJECTIVE: The aim of this study was to assess
      the performance of the EuroSCORE II to predict mortality in patients undergoing
      coronary artery bypass grafts or valve surgery at our institution. METHODS: One
      thousand consecutive patients operated on coronary artery bypass grafts or valve
      surgery, between October 2008 and July 2009, were analyzed. The outcome of
      interest was in-hospital mortality. Calibration was performed by correlation
      between observed and expected mortality by Hosmer Lemeshow. Discrimination was
      calculated by the area under the ROC curve. The performance of the EuroSCORE II
      was compared with the EuroSCORE and InsCor (local model). RESULTS: In
      calibration, the Hosmer Lemeshow test was inappropriate for the EuroSCORE II
      (P=0.0003) and good for the EuroSCORE (P=0.593) and InsCor (P=0.184). However,
      the discrimination, the area under the ROC curve for EuroSCORE II was 0.81 [95%
      CI (0.76 to 0.85), P<0.001], for the EuroSCORE was 0.81 [95% CI (0.77 to 0.86),
      P<0.001] and for InsCor was 0.79 [95% CI (0.74-0.83), P<0.001] showing up
      properly for all. CONCLUSION: The EuroSCORE II became more complex and
      resemblance to the international literature poorly calibrated to predict
      mortality in patients undergoing coronary artery bypass grafts or valve surgery
      at our institution. These data emphasize the importance of the local model.

PMID- 24896157
TI  - Use of EuroSCORE as a predictor of morbidity after cardiac surgery.
AB  - OBJECTIVE: To evaluate the use of the EuroSCORE as a predictor of postoperative
      morbidity after cardiac surgery. METHODS: We retrospectively analyzed the charts
      of 900 patients operated on and admitted to the intensive care unit
      postoperatively at the Royal Portuguese Hospital of Recife. We included all
      patients with complete medical records, excluding those who died during surgery,
      underwent transplantation or correction of congenital heart disease. We evaluated
      the development of respiratory infection, cerebrovascular accident, and dialysis
      dependent renal failure, and the EuroSCORE was compared in terms of the three
      complications using the Mann-Whitney test. The calibration model for predicting
      the morbidities being studied was evaluated using the test set of Homer-Lemeshow
      goodness. The accuracy of the model was assessed using the area under the ROC
      curve (AUROC). RESULTS: The model showed good calibration in predicting
      respiratory infection, acute renal failure and stroke (P=0.285, P=0.789, P=0.45,
      respectively), with good accuracy for respiratory infection (AUROC=0.710 and
      P<0.001) and dialysis-dependent renal failure (AUROC=0.834 and P<0.001), but no
      accuracy to predict stroke (AUROC=0.519). The high-risk patients were more likely
      to develop respiratory infection (OR=9.05, P<0.001) and dialysis-dependent renal
      failure (OR=39.6, P<0.001). The probability of developing respiratory infection
      and dialysis-dependent renal failure was less than 10% with EuroSCORE up to 7 and
      more than 70% with EuroSCORE greater than 15. CONCLUSION: EuroSCORE proved to be
      a good predictor of major postoperative morbidity in cardiac surgery: respiratory
      and dialysis-dependent renal failure.

PMID- 24896158
TI  - Surgical treatment of aortic valve endocarditis: a 26-year experience.
AB  - OBJECTIVE: We have retrospectively analyzed the results of the operations made
      for aortic valve endocarditis in a single center in 26 years. METHODS: From June
      1985 to January 2011, 174 patients were operated for aortic valve endocarditis.
      One hundred and thirty-eight (79.3%) patients were male and the mean age was
      39.3+/-14.4 (9-77) years. Twenty-seven (15.5%) patients had prosthetic valve
      endocarditis. The mean duration of follow-up was 7.3+/-4.2 years (0.1-18.2)
      adding up to a total of 1030.8 patient/years. RESULTS: Two hundred and eighty-two
      procedures were performed. The most frequently performed procedure was aortic
      valve replacement with mechanical prosthesis (81.6%). In-hospital mortality
      occurred in 27 (15.5%) cases. Postoperatively, 25 (14.4%) patients had low
      cardiac output and 17 (9.8%) heart block. The actuarial survival rates for 10 and
      15 years were 74.6+/-3.7% and 61.1+/-10.3%, respectively. In-hospital mortality
      was found to be associated with female gender, emergency operation, postoperative
      renal failure and low cardiac output. The long term mortality was significantly
      associated with mitral valve involvement. Male gender was found to be a
      significant risk factor for recurrence in the follow-up. CONCLUSION: Surgery for
      aortic valve endocarditis has significant mortality. Emergency operation, female
      gender, postoperative renal failure and low cardiac output are significant risk
      factors. Risk for recurrence and need for reoperation is low.

PMID- 24896159
TI  - IL-10 and ET-1 as biomarkers of rheumatic valve disease.
AB  - OBJECTIVE: To evaluate the immunological profile and gene expression of
      endothelin-1 (ET-1) in mitral valves of patients with rheumatic fever originated
      from a reference service in cardiovascular surgery. METHODS: This was a
      quantitative, observational and cross-sectional study. Thirty-five subjects
      (divided into four groups) participated in the study, 25 patients with chronic
      rheumatic heart disease and ten control subjects. The mean age of the sample
      studied was 34.5 years. Seventeen of them (48.58%) were male and 18 (51.42%) were
      female. Inflammatory cytokines (TNF-alpha, IL-4 and IL-10) were measured and ten
      mitral valves of patients who underwent first valve replacement were collected
      for determination of gene expression of endothelin-1 by real time PCR. RESULTS:
      Among the groups studied (patients vs. controls), there was a statistically
      significant difference in IL-10 levels (P=0.002), and no differences in other
      cytokines. Expression of endothelin-1 was observed in 70% of samples.
      Quantitatively, average of ET-1 expression was 62.85+/-25.63%. CONCLUSION:
      Inflammatory cytokine IL-10 participates in the maintenance of chronicity of
      rheumatic fever in patients who underwent valve replacement and those who are
      undergoing medical treatment. The expression of endothelin-1 in heart valve
      lesions in patients undergoing mitral valve replacement confirms its association
      with inflammatory activity in rheumatic fever.

PMID- 24896160
TI  - Cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy:
      long-term follow up.
AB  - INTRODUCTION: Chagas disease is a major cause of cardiomyopathy and sudden death
      in our country. It has a high mortality when their patients develop New York
      Heart Association (NYHA) class IV. OBJECTIVE: The objective of this study is to
      analyze the clinical outcome of patients with Chagas' cardiomyopathy with
      congestive heart failure with optimized pharmacological therapy, undergoing
      cardiac resynchronization therapy. METHODS: Between January 2004 and February
      2009, 72 patients with Chagas' cardiomyopathy in NYHA class III and IV underwent
      cardiac resynchronization therapy and were monitored to assess their clinical
      evolution. We used the t test or the Wilcoxon test to compare the same variable
      in two different times. A P value < 0.05 was established as statistically
      significant. RESULTS: The average clinical follow-up was 46.6 months (range 4-79
      months). At the end of the evaluation, 87.4% of patients were in NYHA class I or
      II (P<0.001). There was response to therapy in 65.3% of patients (P<0.001), with
      an overall mortality of 34.7%. CONCLUSION: In patients with chronic Chagas
      cardiomyopathy undergoing cardiac resynchronization therapy, we found the
      following statistically significant changes: improvement in NYHA class and
      increase of left ventricle ejection fraction, a decrease of the systolic final
      diameter and systolic final left ventricle volume and improvement of patient
      survival.

PMID- 24896161
TI  - Evaluation of patients' quality of life aspects after cardiac pacemaker
      implantation.
AB  - OBJECTIVE: To evaluate patients' quality of life aspects after pacemaker
      implantation, relating it to gender, age, and implantation timespan. METHODS: A
      total of 107 clinically stable patients of both genders (49.5% women and 50.5%
      men) over 18 years old (average 69.3+/-12.6 years) and presenting an implantation
      timespan of three to 12 months (average 6.36A+/-2.99 months) were evaluated. The
      evaluation included personal, clinical, and implant data as well as quality of
      life questionnaires (AQUAREL and SF-36). Statistical analysis was conducted using
      the t test and Pearson correlation, with a 5% significance level. RESULTS: The
      lowest SF-36 score referred to physical aspects, and the highest score referred
      to social aspects. In AQUAREL, the lowest score referred to dyspnea, and the
      highest referred to discomfort. There was a significant association between
      gender and quality of life in SF-36 (physical functioning and emotional aspects)
      and in AQUAREL (dyspnea). A negative correlation was observed between age and
      quality of life (functional capacity in SF-36, and discomfort in AQUAREL) in
      relation to implantation timespan, a correlation with vitality from SF-36.
      CONCLUSION: Lower quality of life scores were found in physical aspects and
      dyspnea; and higher scores in social aspects and discomfort. Men presented higher
      quality of life scores related to physical functioning, emotional aspects and
      dyspnea. As age increases, quality of life worsens regarding functional capacity
      and discomfort; and the longer the pacemaker implantation timespan, the worse
      quality of life when it comes to vitality. Gender, age, and implantation timespan
      influence quality of life; thus, these variables must be considered in strategies
      for improving quality of life of patients with pacemakers.

PMID- 24896162
TI  - Advanced age and incidence of atrial fibrillation in the postoperative period of
      aortic valve replacement.
AB  - OBJECTIVE: This study aims to describe the correlation between age and occurrence
      of atrial fibrillation after aortic stenosis surgery in the elderly as well as
      evaluate the influence of atrial fibrillation on the incidence of strokes,
      hospital length of stay, and hospital mortality. METHODS: Cross-sectional
      retrospective study of > 70 year-old patients who underwent isolated aortic valve
      replacement. RESULTS: 348 patients were included in the study (mean age 76.8+/
      4.6 years). Overall, post-operative atrial fibrillation was 32.8% (n=114), but it
      was higher in patients aged 80 years and older (42.9% versus 28.8% in patients
      aged 70-79 years, P=0.017). There was borderline significance for linear
      correlation between age and atrial fibrillation (P=0.055). Intensive Care Unit
      and hospital lengths of stay were significantly increased in atrial fibrillation
      (P<0.001), but there was no increase in mortality or stroke associated with
      atrial fibrillation. CONCLUSION: Post-operative atrial fibrillation incidence in
      aortic valve replacement is high and correlates with age in patients aged 70
      years and older and significantly more pronounced in patients aged 80 years.
      There was increased length of stay at Intensive Care Unit and hospital, but there
      was no increase in mortality or stroke. These data are important for planning
      prophylaxis and early treatment for this subgroup.

PMID- 24896163
TI  - Evaluation of the Society of Thoracic Surgeons score system for isolated coronary
      bypass graft surgery in a Brazilian population.
AB  - OBJECTIVE: Report the experience with the Society of Thoracic Surgeons scoring
      system in a Brazilian population submitted to isolated coronary artery bypass
      graft surgery. METHODS: Data were collected from January-2010 to December-2011,
      and analyzed to determine the performance of the Society of Thoracic Surgeons
      scoring system on the determination of postoperative mortality and morbidity,
      using the method of the receiver operating characteristic curve as well as the
      Hosmer-Lemeshow and the Chi-square goodness of fit tests. From the 1083 cardiac
      surgeries performed during the study period 659 represented coronary artery
      bypass graft procedures which are included in the present analysis. Mean age was
      61.4 years and 77% were men. RESULTS: Goodness of fit tests have shown good
      calibration indexes both for mortality (X2=6.78, P=0.56) and general morbidity
      (X2=6.69, P=0.57). Analysis of area under the ROC-curve (AUC) demonstrated a good
      performance to detect the risk of death (AUC 0.76; P<0.001), renal failure (AUC
      0.79; P<0.001), prolonged ventilation (AUC 0.80; P<0.001), reoperation (AUC 0.76;
      P<0.001) and major morbidity (AUC 0.75; P<0.001) which represents the combination
      of the assessed postoperative complications. STS scoring system did not present
      comparable results for short term hospital stay, prolonged length of hospital
      stay and could not be properly tested for stroke and wound infection. CONCLUSION:
      Society of Thoracic Surgeons scoring system presented a good calibration and
      discrimination in our population to predict postoperative mortality and the
      majority of the harmful events following coronary artery bypass graft surgery.
      Analysis of larger samples might be needed to further validate the use of the
      score system in Brazilian populations.

PMID- 24896164
TI  - Comparison of the occurrence of thromboembolic and bleeding complications in
      patients with mechanical heart valve prosthesis with one and two leaflets in the
      mitral position.
AB  - INTRODUCTION: Patients with mechanical heart valve prostheses must continuously
      be treated with oral anticoagulants to prevent thromboembolic events related to
      prosthetesis. These patients should be continually evaluated for the control of
      oral anticoagulation. OBJECTIVE: To compare the occurrence of thromboembolic and
      hemorragic complications in patients with mechanical heart valve prosthesis with
      one (mono) and two (bi) leaflets in the mitral position in anticoagulant therapy.
      METHODS: We studied the 10-year interval, 117 patients with prosthesis in the
      mitral position, 48 with prosthetic single leaflet and 69 with two leaflets. We
      evaluated the occurrence of thromboembolic and hemorrhagic major and minor degree
      under gravity. The results are presented in an actuarial study and the frequency
      of occurrence of linear events. RESULTS: The actuarial survival curves showed
      that over time, patients with prosthetic heart valve with one leaflet were less
      free of thromboembolic complications than patients with two leaflet prosthetic
      valve, while the latter (two leaflet) were less free of hemorrhagic accidents.
      The linearized frequency of occurrence of thromboembolism were higher in patients
      with mono leaflet prosthesis. Bleeding rates were higher for patients with bi
      leaflet prosthetic valve. CONCLUSION: Patients with mono leaflet prosthetic heart
      valve showed that they are more prone to the occurrence of serious thromboembolic
      events compared to those with bi leaflet prosthetic valve. Patients with bi
      leaflet prosthetic valve had more bleeding than patients with mono leaflet
      prosthetic valve, however this difference was restricted to the bleeding of minor
      nature.

PMID- 24896166
TI  - Proposal of renal artery's ostial projection under virtual geometric correction
      in infrarenal aneurysms: initial results of a pilot study.
AB  - INTRODUCTION: Endovascular aneurysm repair requires the precise deployment of the
      graft. In order to achieve accurate positioning, the anatomical and morphological
      characteristics of the aorta and its branches is mandatory. Software that perform
      three dimensional reformatting of multislice tomographic images, allow for the
      study of the whole aorto-iliac axis and the perpendicular visualization of the
      origin of the renal arteries. The correct length of the proximal neck can be
      evaluated and adequate graft fixation and sealing may be foreseen. A technique is
      presented, using an software, for the orthogonal correction of the position of
      the renal arteries in relation to the proximal neck, which may guide the
      radioscopic orientation intraoperatively. METHODS: Within a multiplanar
      tomographic image reconstruction, virtual triangulation allows for the three
      dimensional orthogonal correction of the renal arteries' ostia position. The
      predetermined best angulations for visualization are annotated and used for the
      positioning of the surgical C-arm. RESULTS/DISCUSSION: Some authors discuss that
      the anatomic position of the renal vessels seen on the tomographic scan can
      change during the surgical procedure. It is known that the renal arterys' angular
      positioning does not alter, even after insertion of stiff guidewires,
      introducers, and the endograft itself. Therefore, it is possible, using concepts
      of spacial geometry and orthogonal correction, to predict the ideal bidimensional
      intraoperative positioning of the radioscopy device in order to reproduce the
      optimized renal artery ostial projection, ensuring the best accuracy during
      endograft deployment. CONCLUSION: As closer to the tomographic reproduction was
      the radioscopic correction, more careful is the visualization of the ostium of
      the renal artery, better is the exploitation of the lap for fixing and sealing
      and the endoprosthesis deployment is more accurate.

PMID- 24896165
TI  - Effects of periodontal therapy on C-reactive protein and HDL in serum of subjects
      with periodontitis.
AB  - OBJECTIVE: To investigate the effects of nonsurgical periodontal therapy on
      levels of high-sensitivity C-reactive protein in the sera and its association
      with body mass index and high density lipoprotein in subjects with severe
      periodontitis. METHODS: Sera from 28 subjects (mean age: 34.36+/-6.24; 32% men)
      with severe periodontitis and 27 healthy controls (mean age: 33.18+/-6.42; 33%
      men) were collected prior to periodontal therapy. Blood samples were obtained
      from 23 subjects who completed therapy (9-12 months). Oral and systemic
      parameters such as the number of blood cells, glucose examination, lipid profile,
      and high-sensitivity C-reactive protein levels accessed by high-sensitivity
      immunonephelometry assay, were included. RESULTS: Before therapy, in the
      periodontitis group, the ratio of subjects with high-sensitivity C-reactive
      protein <0.3 mg/dL was statistically lower than in the control group (P<0.0216).
      After therapy, the ratio of subjects with high-sensitivity C-reactive protein
      <0.3 mg/dL was significantly higher (65.22%) (P<0.0339). The mean value for body
      mass index was statistically lower in subjects with high-sensitivity C-reactive
      protein <0.3 mg/dL (24.63+/-4.19), compared with those with high-sensitivity C
      reactive protein >0.3 mg/dL (28.91+/-6.03) (P<0.0411). High density lipoprotein
      presented a mean value statistically higher after therapy (P<0.0027). CONCLUSION:
      In systemically healthy subjects with periodontitis, periodontal therapy was
      associated with decreased levels of circulating high-sensitivity C-reactive
      protein and increase of high density lipoprotein in serum. The clinical trial was
      registered at http://www.clinicaltrials.gov.br/, No. RBR-24T799.

PMID- 24896167
TI  - Comparison of the solution of histidine-tryptophan-alfacetoglutarate with
      histidine-tryptophan-glutamate as cardioplegic agents in isolated rat hearts: an
      immunohistochemical study.
AB  - INTRODUCTION: Cardiac arrest during heart surgery is a common procedure and
      allows the surgeon to perform surgical procedures in an environment free of blood
      and movement. Using a model of isolated rat heart, the authors compare a new
      cardioplegic solution containing histidine-tryptophan-glutamate (group 2) with
      the histidine-tryptophan-alphacetoglutarate (group 1) routinely used by some
      cardiac surgeons. OBJECTIVE: To assess caspase, IL-8 and KI-67 in isolated rat
      hearts using immunohistochemistry. METHODS: 20 Wistar male rats were anesthetized
      and heparinized. The chest was opened, cardioctomy was performed and 40 ml/kg of
      the appropriate cardioplegic solution was infused. The hearts were kept for 2
      hours at 4oC in the same solution, and thereafter, placed in the Langendorff
      apparatus for 30 minutes with Ringer-Locke solution. Immunohistochemistry
      analysis of caspase, IL-8, and KI-67 were performed. RESULTS: The concentration
      of caspase was lower in group 2 and Ki-67 was higher in group 2, both P<0.05.
      There was no statistical difference between the values of IL-8 between the
      groups. CONCLUSION: Histidine-tryptophan-glutamate solution was better than
      histidine-tryptophan-alphacetoglutarate solution because it reduced caspase
      (apoptosis), increased KI-67 (cell proliferation), and showed no difference in IL
      8 levels compared to group 1. This suggests that the histidine-tryptophan
      glutamate solution was more efficient than the histidine-tryptophan
      alphacetoglutarate for the preservation of hearts of rat cardiomyocytes.

PMID- 24896168
TI  - Information technology implementing globalization on strategies for quality care
      provided to children submitted to cardiac surgery: International Quality
      Improvement Collaborative Program--IQIC.
AB  - INTRODUCTION: Congenital heart diseases are the world's most common major birth
      defect, affecting one in every 120 children. Ninety percent of these children are
      born in areas where appropriate medical care is inadequate or unavailable.
      OBJECTIVE: To share knowledge and experience between an international center of
      excellence in pediatric cardiac surgery and a related program in Brazil. METHODS:
      The strategy used by the program was based on long-term technological and
      educational support models used in that center, contributing to the creation and
      implementation of new programs. The Telemedicine platform was used for real-time
      monthly broadcast of themes. A chat software was used for interaction between
      participating members and the group from the center of excellence. RESULTS:
      Professionals specialized in care provided to the mentioned population had the
      opportunity to share to the knowledge conveyed. CONCLUSION: It was possible to
      observe that the technological resources that implement the globalization of
      human knowledge were effective in the dissemination and improvement of the team
      regarding the care provided to children with congenital heart diseases.

PMID- 24896170
TI  - Transfixing cardiac injury with perforations in stomach, diaphragm and lung:
      unusual scenario in penetrating trauma.
AB  - A 23-year-old man suffered a penetrating injury caused by a metallic fragment
      thrown from a grass-cutting tool, resulting in perforating injuries in the
      stomach, diaphragm, heart, and lungs. 

PMID- 24896169
TI  - Managing the inflammatory response after cardiopulmonary bypass: review of the
      studies in animal models.
AB  - OBJECTIVE: To review studies performed in animal models that evaluated
      therapeutic interventions to inflammatory response and microcirculatory changes
      after cardiopulmonary bypass. METHODS: It was used the search strategy
      ("Cardiopulmonary Bypass" (MeSH)) and ("Microcirculation" (MeSH) or
      "Inflammation" (MeSH) or "Inflammation Mediators" (MeSH)). Repeated results,
      human studies, non-English language articles, reviews and studies without control
      were excluded. RESULTS: Blood filters, system miniaturization, specific primers
      regional perfusion, adequate flow and temperature and pharmacological therapies
      with anticoagulants, vasoactive drugs and anti-inflammatories reduced changes in
      microcirculation and inflammatory response. CONCLUSION: Demonstrated efficacy in
      animal models establishes a perspective for evaluating these interventions in
      clinical practice.

PMID- 24896171
TI  - Mammary artery harvesting using the Da Vinci Si robotic system.
AB  - Internal mammary artery harvesting is an essential part of any coronary artery
      bypass operation. Totally endoscopic coronary artery bypass graft surgery has
      become reality in many centers as a safe and effective alternative to
      conventional surgery in selected patients. Internal mammary artery harvesting is
      the initial part of the procedure and should be performed equally safely if one
      wants to achieve excellence in patency rates for the bypass. We here describe the
      technique for mammary harvesting with the Da Vinci Si robotic system. 

PMID- 24896172
TI  - Comments on "Innovation and excellence: changing to prevail the Brazilian
      cardiovascular surgery".

PMID- 24896173
TI  - BJCVS has record access in 2013.

PMID- 24896175
TI  - Cardiovascular and periodontal diseases.

PMID- 24896174
TI  - Cardiac resynchronization therapy for patients with chronic systolic heart
      failure secondary to Chagas cardiomyopathy in the 21st century.

PMID- 24896176
TI  - Effects of microtubule mechanics on hydrolysis and catastrophes.
AB  - We introduce a model for microtubule (MT) mechanics containing lateral bonds
      between dimers in neighboring protofilaments, bending rigidity of dimers, and
      repulsive interactions between protofilaments modeling steric constraints to
      investigate the influence of mechanical forces on hydrolysis and catastrophes. We
      use the allosteric dimer model, where tubulin dimers are characterized by an
      equilibrium bending angle, which changes from 0 degrees  to 22 degrees  by
      hydrolysis of a dimer. This also affects the lateral interaction and bending
      energies and, thus, the mechanical equilibrium state of the MT. As hydrolysis
      gives rise to conformational changes in dimers, mechanical forces also influence
      the hydrolysis rates by mechanical energy changes modulating the hydrolysis rate.
      The interaction via the MT mechanics then gives rise to correlation effects in
      the hydrolysis dynamics, which have not been taken into account before. Assuming
      a dominant influence of mechanical energies on hydrolysis rates, we investigate
      the most probable hydrolysis pathways both for vectorial and random hydrolysis.
      Investigating the stability with respect to lateral bond rupture, we identify
      initiation configurations for catastrophes along the hydrolysis pathways and
      values for a lateral bond rupture force. If we allow for rupturing of lateral
      bonds between dimers in neighboring protofilaments above this threshold force,
      our model exhibits avalanche-like catastrophe events.

PMID- 24896177
TI  - Particle physics: The hunt for Majorana neutrinos hots up.

PMID- 24896178
TI  - Genome sequencing identifies major causes of severe intellectual disability.
AB  - Severe intellectual disability (ID) occurs in 0.5% of newborns and is thought to
      be largely genetic in origin. The extensive genetic heterogeneity of this
      disorder requires a genome-wide detection of all types of genetic variation.
      Microarray studies and, more recently, exome sequencing have demonstrated the
      importance of de novo copy number variations (CNVs) and single-nucleotide
      variations (SNVs) in ID, but the majority of cases remain undiagnosed. Here we
      applied whole-genome sequencing to 50 patients with severe ID and their
      unaffected parents. All patients included had not received a molecular diagnosis
      after extensive genetic prescreening, including microarray-based CNV studies and
      exome sequencing. Notwithstanding this prescreening, 84 de novo SNVs affecting
      the coding region were identified, which showed a statistically significant
      enrichment of loss-of-function mutations as well as an enrichment for genes
      previously implicated in ID-related disorders. In addition, we identified eight
      de novo CNVs, including single-exon and intra-exonic deletions, as well as
      interchromosomal duplications. These CNVs affected known ID genes more frequently
      than expected. On the basis of diagnostic interpretation of all de novo variants,
      a conclusive genetic diagnosis was reached in 20 patients. Together with one
      compound heterozygous CNV causing disease in a recessive mode, this results in a
      diagnostic yield of 42% in this extensively studied cohort, and 62% as a
      cumulative estimate in an unselected cohort. These results suggest that de novo
      SNVs and CNVs affecting the coding region are a major cause of severe ID. Genome
      sequencing can be applied as a single genetic test to reliably identify and
      characterize the comprehensive spectrum of genetic variation, providing a genetic
      diagnosis in the majority of patients with severe ID. 

PMID- 24896179
TI  - The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy.
AB  - Cells maintain healthy mitochondria by degrading damaged mitochondria through
      mitophagy; defective mitophagy is linked to Parkinson's disease. Here we report
      that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy
      driven by the ubiquitin ligase parkin (also known as PARK2) and protein kinase
      PINK1, which are encoded by two genes associated with Parkinson's disease. Parkin
      ubiquitinates and tags damaged mitochondria for clearance. Overexpression of
      USP30 removes ubiquitin attached by parkin onto damaged mitochondria and blocks
      parkin's ability to drive mitophagy, whereas reducing USP30 activity enhances
      mitochondrial degradation in neurons. Global ubiquitination site profiling
      identified multiple mitochondrial substrates oppositely regulated by parkin and
      USP30. Knockdown of USP30 rescues the defective mitophagy caused by pathogenic
      mutations in parkin and improves mitochondrial integrity in parkin- or PINK1
      deficient flies. Knockdown of USP30 in dopaminergic neurons protects flies
      against paraquat toxicity in vivo, ameliorating defects in dopamine levels, motor
      function and organismal survival. Thus USP30 inhibition is potentially beneficial
      for Parkinson's disease by promoting mitochondrial clearance and quality control.

PMID- 24896180
TI  - BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor
      PCID2.
AB  - Genome instability is central to ageing, cancer and other diseases. It is not
      only proteins involved in DNA replication or the DNA damage response (DDR) that
      are important for maintaining genome integrity: from yeast to higher eukaryotes,
      mutations in genes involved in pre-mRNA splicing and in the biogenesis and export
      of messenger ribonucleoprotein (mRNP) also induce DNA damage and genome
      instability. This instability is frequently mediated by R-loops formed by DNA-RNA
      hybrids and a displaced single-stranded DNA. Here we show that the human TREX-2
      complex, which is involved in mRNP biogenesis and export, prevents genome
      instability as determined by the accumulation of gamma-H2AX (Ser-139
      phosphorylated histone H2AX) and 53BP1 foci and single-cell electrophoresis in
      cells depleted of the TREX-2 subunits PCID2, GANP and DSS1. We show that the
      BRCA2 repair factor, which binds to DSS1, also associates with PCID2 in the cell.
      The use of an enhanced green fluorescent protein-tagged hybrid-binding domain of
      RNase H1 and the S9.6 antibody did not detect R-loops in TREX-2-depleted cells,
      but did detect the accumulation of R-loops in BRCA2-depleted cells. The results
      indicate that R-loops are frequently formed in cells and that BRCA2 is required
      for their processing. This link between BRCA2 and RNA-mediated genome instability
      indicates that R-loops may be a chief source of replication stress and cancer
      associated instability. 

PMID- 24896181
TI  - Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1
      mechanisms.
AB  - Srs2 helicase is known to dismantle nucleofilaments of Rad51 recombinase to
      prevent spurious recombination events and unwind trinucleotide sequences that are
      prone to hairpin formation. Here we document a new, unexpected genome maintenance
      role of Srs2 in the suppression of mutations arising from mis-insertion of
      ribonucleoside monophosphates during DNA replication. In cells lacking RNase H2,
      Srs2 unwinds DNA from the 5' side of a nick generated by DNA topoisomerase I at a
      ribonucleoside monophosphate residue. In addition, Srs2 interacts with and
      enhances the activity of the nuclease Exo1, to generate a DNA gap in preparation
      for repair. Srs2-Exo1 thus functions in a new pathway of nick processing-gap
      filling that mediates tolerance of ribonucleoside monophosphates in the genome.
      Our results have implications for understanding the basis of Aicardi-Goutieres
      syndrome, which stems from inactivation of the human RNase H2 complex. 

PMID- 24896182
TI  - Genome-scale functional characterization of Drosophila developmental enhancers in
      vivo.
AB  - Transcriptional enhancers are crucial regulators of gene expression and animal
      development and the characterization of their genomic organization,
      spatiotemporal activities and sequence properties is a key goal in modern
      biology. Here we characterize the in vivo activity of 7,705 Drosophila
      melanogaster enhancer candidates covering 13.5% of the non-coding non-repetitive
      genome throughout embryogenesis. 3,557 (46%) candidates are active, suggesting a
      high density with 50,000 to 100,000 developmental enhancers genome-wide. The vast
      majority of enhancers display specific spatial patterns that are highly dynamic
      during development. Most appear to regulate their neighbouring genes, suggesting
      that the cis-regulatory genome is organized locally into domains, which are
      supported by chromosomal domains, insulator binding and genome evolution.
      However, 12 to 21 per cent of enhancers appear to skip non-expressed neighbours
      and regulate a more distal gene. Finally, we computationally identify cis
      regulatory motifs that are predictive and required for enhancer activity, as we
      validate experimentally. This work provides global insights into the organization
      of an animal regulatory genome and the make-up of enhancer sequences and confirms
      and generalizes principles from previous studies. All enhancer patterns are
      annotated manually with a controlled vocabulary and all results are available
      through a web interface (http://enhancers.starklab.org), including the raw images
      of all microscopy slides for manual inspection at arbitrary zoom levels. 

PMID- 24896184
TI  - Cell biology: balancing act.

PMID- 24896183
TI  - Engineering a memory with LTD and LTP.
AB  - It has been proposed that memories are encoded by modification of synaptic
      strengths through cellular mechanisms such as long-term potentiation (LTP) and
      long-term depression (LTD). However, the causal link between these synaptic
      processes and memory has been difficult to demonstrate. Here we show that fear
      conditioning, a type of associative memory, can be inactivated and reactivated by
      LTD and LTP, respectively. We began by conditioning an animal to associate a foot
      shock with optogenetic stimulation of auditory inputs targeting the amygdala, a
      brain region known to be essential for fear conditioning. Subsequent optogenetic
      delivery of LTD conditioning to the auditory input inactivates memory of the
      shock. Then subsequent optogenetic delivery of LTP conditioning to the auditory
      input reactivates memory of the shock. Thus, we have engineered inactivation and
      reactivation of a memory using LTD and LTP, supporting a causal link between
      these synaptic processes and memory. 

PMID- 24896185
TI  - Population health: immaturity in the gut microbial community.

PMID- 24896187
TI  - Persistent gut microbiota immaturity in malnourished Bangladeshi children.
AB  - Therapeutic food interventions have reduced mortality in children with severe
      acute malnutrition (SAM), but incomplete restoration of healthy growth remains a
      major problem. The relationships between the type of nutritional intervention,
      the gut microbiota, and therapeutic responses are unclear. In the current study,
      bacterial species whose proportional representation define a healthy gut
      microbiota as it assembles during the first two postnatal years were identified
      by applying a machine-learning-based approach to 16S ribosomal RNA data sets
      generated from monthly faecal samples obtained from birth onwards in a cohort of
      children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently
      healthy growth. These age-discriminatory bacterial species were incorporated into
      a model that computes a 'relative microbiota maturity index' and 'microbiota-for
      age Z-score' that compare postnatal assembly (defined here as maturation) of a
      child's faecal microbiota relative to healthy children of similar chronologic
      age. The model was applied to twins and triplets (to test for associations of
      these indices with genetic and environmental factors, including diarrhoea),
      children with SAM enrolled in a randomized trial of two food interventions, and
      children with moderate acute malnutrition. Our results indicate that SAM is
      associated with significant relative microbiota immaturity that is only partially
      ameliorated following two widely used nutritional interventions. Immaturity is
      also evident in less severe forms of malnutrition and correlates with
      anthropometric measurements. Microbiota maturity indices provide a microbial
      measure of human postnatal development, a way of classifying malnourished states,
      and a parameter for judging therapeutic efficacy. More prolonged interventions
      with existing or new therapeutic foods and/or addition of gut microbes may be
      needed to achieve enduring repair of gut microbiota immaturity in childhood
      malnutrition and improve clinical outcomes. 

PMID- 24896188
TI  - C. elegans Punctin specifies cholinergic versus GABAergic identity of
      postsynaptic domains.
AB  - Because most neurons receive thousands of synaptic inputs, the neuronal membrane
      is a mosaic of specialized microdomains where neurotransmitter receptors cluster
      in register with the corresponding presynaptic neurotransmitter release sites. In
      many cases the coordinated differentiation of presynaptic and postsynaptic
      domains implicates trans-synaptic interactions between membrane-associated
      proteins such as neurexins and neuroligins. The Caenorhabditis elegans
      neuromuscular junction (NMJ) provides a genetically tractable system in which to
      analyse the segregation of neurotransmitter receptors, because muscle cells
      receive excitatory innervation from cholinergic neurons and inhibitory
      innervation from GABAergic neurons. Here we show that Ce-Punctin/madd-4 (ref. 5),
      the C. elegans orthologue of mammalian punctin-1 and punctin-2, encodes neurally
      secreted isoforms that specify the excitatory or inhibitory identity of
      postsynaptic NMJ domains. These proteins belong to the ADAMTS (a disintegrin and
      metalloprotease with thrombospondin repeats)-like family, a class of
      extracellular matrix proteins related to the ADAM proteases but devoid of
      proteolytic activity. Ce-Punctin deletion causes the redistribution of synaptic
      acetylcholine and GABAA (gamma-aminobutyric acid type A) receptors into
      extrasynaptic clusters, whereas neuronal presynaptic boutons remain unaltered.
      Alternative promoters generate different Ce-Punctin isoforms with distinct
      functions. A short isoform is expressed by cholinergic and GABAergic motoneurons
      and localizes to excitatory and inhibitory NMJs, whereas long isoforms are
      expressed exclusively by cholinergic motoneurons and are confined to cholinergic
      NMJs. The differential expression of these isoforms controls the congruence
      between presynaptic and postsynaptic domains: specific disruption of the short
      isoform relocalizes GABAA receptors from GABAergic to cholinergic synapses,
      whereas expression of a long isoform in GABAergic neurons recruits acetylcholine
      receptors to GABAergic NMJs. These results identify Ce-Punctin as a previously
      unknown synaptic organizer and show that presynaptic and postsynaptic domain
      identities can be genetically uncoupled in vivo. Because human punctin-2 was
      identified as a candidate gene for schizophrenia, ADAMTS-like proteins may also
      control synapse organization in the mammalian central nervous system. 

PMID- 24896190
TI  - Plasma malondialdehyde levels in children on 12-hour cyclic parenteral nutrition:
      are there health risks?
AB  - In children undergoing total parenteral nutrition (PN), lipids provide a key
      source of calories preventing or correcting energy deficits and improving
      outcomes. However, some of these lipids may undergo oxidation leading to the
      formation of malondialdehyde (MDA), a cytotoxic byproduct found in these
      patients. This paper aims to describe a sensitive method for detecting MDA and
      discuss its role in certain diseases commonly found in children on regular PN. To
      quantify MDA levels in children benefitting from long-term cyclic PN, a reliable
      and sensitive high-performance liquid chromatographic method based on a 1-step
      derivatization/extraction procedure analysis with ultraviolet determination at
      305 nm wavelength was achieved. In control children without PN, MDA levels were
      on average 3.30 +/- 0.08 uM. However, in children nourished intravenously by fat
      emulsion for a long time, in which liver problems have been identified, the
      circulating concentrations of MDA ranged widely at both the start and the end of
      a session, 3- to 10-fold, respectively, in comparison with the levels measured in
      controls. This finding indicates that PN administrated long term raises plasma
      MDA levels, indicating chronic exposure and therefore a possible health risk,
      particularly liver damage. This preliminary study using a limited number of
      patients and controls showed that children undergoing long-term PN are strongly
      exposed to MDA, which must be considered as a potent toxic compound rather than a
      simple marker of lipid peroxidation.

PMID- 24896191
TI  - Comparing major alkaloids of Fritillariae Hupehensis Bulbs (FHB) and congeneric
      plants by HPLC-ELSD and HPLC-ESI-MS(n).
AB  - In the study, the major alkaloids from Fritillariae Hupehensis Bulbs (FHB) have
      been analysed for the first time by the combined use of the following two
      methods: the simultaneous quantitation of three alkaloids by using high
      performance liquid chromatography coupled with evaporative light scattering
      detector (HPLC-ELSD) and the simultaneous characterisation of seven alkaloids by
      using HPLC coupled with electrospray ionisation-mass spectrometry analysers
      detection (HPLC-ESI-MS(n)). The other four congeneric species were compared by
      using the established method. Both correlation coefficients of similarity in
      chromatograms were calculated for quantitative expression of HPLC profiles. The
      results revealed that the chromatogram profile combining similarity evaluation
      could efficiently identify and distinguish FHB from other different origins of
      Fritillaria species. The established method was considered to be suitable for
      checking the genuine origin and quality control of FHB.

PMID- 24896186
TI  - Novel somatic and germline mutations in intracranial germ cell tumours.
AB  - Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain
      tumours that are clinically and histologically similar to the more common gonadal
      GCTs. IGCTs show great variation in their geographical and gender distribution,
      histological composition and treatment outcomes. The incidence of IGCTs is
      historically five- to eightfold greater in Japan and other East Asian countries
      than in Western countries, with peak incidence near the time of puberty. About
      half of the tumours are located in the pineal region. The male-to-female
      incidence ratio is approximately 3-4:1 overall, but is even higher for tumours
      located in the pineal region. Owing to the scarcity of tumour specimens available
      for research, little is currently known about this rare disease. Here we report
      the analysis of 62 cases by next-generation sequencing, single nucleotide
      polymorphism array and expression array. We find the KIT/RAS signalling pathway
      frequently mutated in more than 50% of IGCTs, including novel recurrent somatic
      mutations in KIT, its downstream mediators KRAS and NRAS, and its negative
      regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy
      number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding
      upregulation of AKT1 expression. We identified loss-of-function mutations in
      BCORL1, a transcriptional co-repressor and tumour suppressor. We report
      significant enrichment of novel and rare germline variants in JMJD1C, which codes
      for a histone demethylase and is a coactivator of the androgen receptor, among
      Japanese IGCT patients. This study establishes a molecular foundation for
      understanding the biology of IGCTs and suggests potentially promising therapeutic
      strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR
      pathway. 

PMID- 24896189
TI  - Search for Majorana neutrinos with the first two years of EXO-200 data.
AB  - Many extensions of the standard model of particle physics suggest that neutrinos
      should be Majorana-type fermions-that is, that neutrinos are their own anti
      particles-but this assumption is difficult to confirm. Observation of
      neutrinoless double-beta decay (0nubetabeta), a spontaneous transition that may
      occur in several candidate nuclei, would verify the Majorana nature of the
      neutrino and constrain the absolute scale of the neutrino mass spectrum. Recent
      searches carried out with (76)Ge (the GERDA experiment) and (136)Xe (the KamLAND
      Zen and EXO (Enriched Xenon Observatory)-200 experiments) have established the
      lifetime of this decay to be longer than 10(25) years, corresponding to a limit
      on the neutrino mass of 0.2-0.4 electronvolts. Here we report new results from
      EXO-200 based on a large (136)Xe exposure that represents an almost fourfold
      increase from our earlier published data sets. We have improved the detector
      resolution and revised the data analysis. The half-life sensitivity we obtain is
      1.9 * 10(25) years, an improvement by a factor of 2.7 on previous EXO-200
      results. We find no statistically significant evidence for 0nubetabeta decay and
      set a half-life limit of 1.1 * 10(25) years at the 90 per cent confidence level.
      The high sensitivity holds promise for further running of the EXO-200 detector
      and future 0nubetabeta decay searches with an improved Xe-based experiment, nEXO.

PMID- 24896192
TI  - The risk of a safety-critical event associated with mobile device use in specific
      driving contexts.
AB  - OBJECTIVE: We explored drivers' mobile device use and its associated risk of a
      safety-critical event (SCE) in specific driving contexts. Our premise was that
      the SCE risk associated with mobile device use increases when the driving task
      becomes demanding. METHODS: Data from naturalistic driving studies involving
      commercial motor vehicle drivers and light vehicle drivers were partitioned into
      subsets representative of specific driving contexts. The subsets were generated
      using data set attributes that included level of service and relation to
      junction. These attributes were selected based on exogenous factors known to
      alter driving task demands. The subsets were analyzed using a case-cohort
      approach, which was selected to complement previous investigations of mobile
      device SCE risk using naturalistic driving data. RESULTS: Both commercial motor
      vehicle and light vehicle drivers varied as to how much they conversed on a
      mobile device but did not vary their engagement in visual-manual subtasks.
      Furthermore, commercial motor vehicle drivers conversed less frequently as the
      driving task demands increased, whereas light vehicle drivers did not. The risk
      of an SCE associated with mobile device use was dependent on the subtask
      performed and the driving context. Only visual-manual subtasks were associated
      with an increased SCE risk, whereas conversing was associated with a decreased
      risk in some driving contexts. CONCLUSION: Drivers' engagement in mobile device
      subtasks varies by driving context. The SCE risk associated with mobile device
      use is dependent on the types of subtasks performed and the driving context. The
      findings of this exploratory study can be applied to the design of driver-vehicle
      interfaces that mitigate distraction by preventing visual-manual subtasks while
      driving.

PMID- 24896193
TI  - Immunochromatographic strip assay for the rapid and sensitive detection of
      Salmonella Typhimurium in artificially contaminated tomato samples.
AB  - This study was designed to confirm the applicability of a liposome-based
      immunochromatographic assay for the rapid detection of Salmonella enterica subsp.
      enterica serovar Typhimurium (Salmonella Typhimurium) in artificially
      contaminated tomato samples. To determine the detection limit and pre-enrichment
      incubation time (10, 12, and 18 h pre-enrichment in 1% buffered peptone water),
      the tests were performed with different cell numbers of Salmonella Typhimurium (3
      * 10(0), 3 * 10(1), 3 * 10(2), and 3 * 10(3) CFU.mL(-1)) inoculated into 25 g of
      crushed tomato samples. The assay was able to detect as few as 30 Salmonella
      Typhimurium cells per 25 g of tomato samples (1.2 cells.g(-1)) after 12 h pre
      enrichment incubation. Moreover, when the developed assay was compared with
      traditional morphological and biochemical culture-based methods as well as
      colloidal gold nanoparticle-based commercial test strips, the developed assay
      yielded positive results for the detection of Salmonella Typhimurium within a
      shorter period time. These findings confirm that the developed assay may have
      practical application for the sensitive detection of Salmonella Typhimurium in
      various food samples, including raw vegetables, with a relatively low detection
      limit and shorter analysis time. 

PMID- 24896194
TI  - Specific inhibitors for identifying pathways for methane production from carbon
      monoxide by a nonadapted anaerobic mixed culture.
AB  - Specific inhibitors such as 2-bromoethanesulfonate (BES) and vancomycin were
      employed in activity batch tests to decipher metabolic pathways that are
      preferentially used by a mixed anaerobic consortium (sludge from an anaerobic
      digester) to transform carbon monoxide (CO) into methane (CH4). We first
      evaluated the inhibitory effect of both BES and vancomycin on the microbial
      community, as well as the efficiency and stability of vancomycin at 35  degrees
      C, over time. The activity tests with CO2-H2, CO, glucose, acetate, formate,
      propionate, butyrate, methanol, and ethanol showed that vancomycin does not
      inhibit some Gram-negative bacteria, and 50 mmol/L BES effectively blocks CH4
      production in the sludge. However, when sludge was incubated with propionate,
      butyrate, methanol, or ethanol as the sole energy and carbon source,
      methanogenesis was only partially inhibited by BES. Separate tests showed that
      0.07 mmol/L vancomycin is enough to maintain its inhibitory efficiency and
      stability in the population for at least 32 days at 35  degrees C. Using the
      inhibitors above, it was demonstrated that CO conversion to CH4 is an indirect, 2
      step process, in which the CO is converted first to acetate and subsequently to
      CH4. 

PMID- 24896195
TI  - In vivo evaluation of Eclipta alba extract as anticancer and multidrug resistance
      reversal agent.
AB  - The present study investigates the anticancer and multidrug resistance (MDR)
      reversal potential of hydro-alcoholic Eclipta alba extract (EAE) through in vivo
      experiments. Diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were used
      for liver cancer induction in animal model, whereas for MDR induction, AAF was
      used. The level of antioxidant enzymes was studied in serum along with
      biochemical parameters. Cancer and MDR-induced liver cells have higher levels of
      reactive oxygen species (ROS) and, in turn, are responsible for the maintenance
      of the cancer phenotype. Treatment with EAE declines the ROS level and revealed
      the ROS scavenging properties. Alfa feto protein levels were found to increase
      significantly in cancer-induced animals confirming induction and progression of
      liver cancer, EAE treatment was found to bring back the altered levels within
      normal range indicating the therapeutic effect of plant extract over liver
      cancer. Zymogram showed the inhibition of MMPs and RT-PCR analysis revealed that
      the mRNA expression of nuclear factor-kB was markedly decreased upon EAE
      treatment. Further, our results showed that EAE could significantly inhibit mdr1
      gene encode P-glycoprotein expression. Our data suggest that EAE is a novel
      anticancer and potent MDR reversal agent and may be a potential adjunctive agent
      for tumor chemotherapy. 

PMID- 24896196
TI  - CT and MRI of primary and metastatic fibrolamellar carcinoma: a case series of 37
      patients.
AB  - OBJECTIVE: Fibrolamellar carcinoma (FLC) is a rare disease, with limited
      radiographic reported information. We assessed the imaging patterns of primary
      and metastatic FLC. METHODS: CT and MR examinations of patients with FLC were
      retrospectively reviewed. Imaging features were assessed for primary and
      recurrent liver tumours, including dimension, enhancement characteristics, and
      presence or absence of central scars. Locations of nodal and extranodal
      metastases were also recorded. RESULTS: Of 37 patients (18 males and 19 females;
      average age, 23.5 years) with FLC, 24 had imaging of their primary tumour; 13 had
      metastases at presentation and 7 developed metastases on follow-up. The remaining
      13 patients had follow-up imaging of metastatic disease. Primary FLC had a mean
      diameter >11 cm, with central scars in ten (46%) patients. Most tumours enhanced
      heterogeneously (96%) and showed arterial enhancement (81%). On MRI, 62% of FLCs
      were hypointense on T1 weighted imaging and 54% were hyperintense on T2 weighted
      imaging. 13 patients (54%) had nodal metastases at presentation, mostly in the
      upper abdomen (92%) and commonly in the chest (38%). Extrahepatic metastases were
      most frequently pulmonary or peritoneal. Predominantly small and homogeneous
      intrahepatic recurrences were detected on follow-up in 15 patients. CONCLUSION:
      FLC often presents as a large hepatic tumour with nodal and distant metastases.
      Thoracic adenopathy and lung metastases were frequently found in our series,
      suggesting the need for pre-operative and follow-up chest imaging. ADVANCES IN
      KNOWLEDGE: Thoracic nodal and lung metastases are common in FLC; therefore,
      dedicated chest imaging should be part of the evaluation of a patient with FLC.

PMID- 24896197
TI  - Breast cancer detection in digital breast tomosynthesis and digital mammography-a
      side-by-side review of discrepant cases.
AB  - OBJECTIVE: To analyse discrepant breast cancer detection in digital breast
      tomosynthesis (DBT) and digital mammography (DM). METHODS: From a previous
      detection study comparing DBT and DM, 26 discrepant cases were extracted, 19
      detected by DBT only and 7 by DM only. An expert panel of three radiologists
      reviewed these cases and documented the level of discrepancy, lesion visibility,
      radiographic pattern and lesion conspicuity and assessed the reason for non
      detection. Differences between groups were tested using the Wilcoxon rank sum
      test, the Kruskal-Wallis test and visual grading characteristics. RESULTS: The
      proportion of lesion periphery in fatty tissue was statistically significantly
      larger, and there were significantly more spiculated masses in DBT compared with
      DM in the DBT only group (p = 0.018; p = 0.015). The main reasons for missing a
      lesion were poor lesion visibility when using DM and interpretative error when
      using DBT. CONCLUSION: Lesion visualization is superior with DBT, particularly of
      spiculated tumours. A major reason for non-detection in DBT seems to be
      interpretative error, which may be due to lack of experience. ADVANCES IN
      KNOWLEDGE: Our findings suggest that DBT is better than DM in visualizing breast
      cancer and that non-detection when using DBT is related to interpretative error
      regarding clearly visible lesions.

PMID- 24896198
TI  - Apparent diffusion coefficient measurements to support a diagnosis of
      intracranial hypotension.
AB  - OBJECTIVE: Intracranial hypotension (ICH) can be a challenging diagnosis, as
      cerebrospinal fluid leaks may be difficult to confirm, patients may have other
      causes for clinical symptoms and imaging findings can be non-specific,
      particularly in the setting of comorbidities. We investigate the use of brain
      diffusion measurements [apparent diffusion coefficient (ADC) values] in the
      assessment of ICH. METHODS: 13 cases of ICH were identified retrospectively based
      on imaging findings and their clinical histories were compared with 13 control
      subjects. Regional ADC values and average diffusion constant (Dav) from brain
      slice ADC histograms were measured. RESULTS: ADC values trended higher in all
      brain regions in patients with ICH than those in control subjects, with
      statistically significant differences in frontal white matter, mid-brain and deep
      grey structures. Dav determined by a single-slice ADC histogram was significantly
      higher in patients with ICH than in the control group (p = 0.008). In two cases
      followed longitudinally, Dav correlated with the patient's symptoms and decreased
      towards normal value with blood patch. In one case, decreased Dav correlated with
      the formation of subdural collections. CONCLUSION: Cerebral oedema as assessed by
      increased ADC is strongly correlated with ICH (10 of 13 cases). Histographic
      analysis of ADC values may offer increased accuracy of ADC measurement. ADC value
      assessment in the determination of ICH may be particularly useful in complex
      clinical cases, where treatment is followed over time or where gadolinium is not
      used and meningeal enhancement cannot be assessed. ADVANCES IN KNOWLEDGE: This
      article investigates the use of brain diffusion measurements in the assessment of
      ICH in the clinical setting.

PMID- 24896200
TI  - Monte Carlo simulations will change the way we treat patients with proton beams
      today.
AB  - Within the past two decades, the evolution of Monte Carlo simulation tools,
      coupled with our better understanding of physics processes and computer
      technology has enabled accurate and efficient prediction of particle interactions
      with tissue. Monte Carlo simulations have now been applied for routine clinical
      applications. This commentary outlines how simulations have the potential to
      change clinical practice particularly in proton therapy. Specifically, Monte
      Carlo simulations will impact treatment outcome analysis, reduce treatment
      volumes and help understand proton-induced radiation biology. 

PMID- 24896199
TI  - Diagnostic accuracy of integrated (18)F-FDG PET/CT for restaging patients with
      malignant germ cell tumours.
AB  - OBJECTIVE: Evaluation of utility of fluorine-18 fludeoxyglucose ((18)F-FDG)
      positron emission tomography/CT (PET/CT) for restaging patients with primary
      malignant germ cell tumours (GCTs). METHODS: Data of 92 patients (age, 31.94 +/-
      10.1 years; male/female, 86/6) with histopathologically confirmed malignant GCTs
      (gonadal, 88; mediastinal, 4; seminomatous, 47 and non-seminomatous, 45) who
      underwent (18)F-FDG PET/CT for restaging (suspected recurrence/post-therapy
      evaluation) were retrospectively analysed. Two experienced nuclear medicine
      physicians reviewed the PET/CT images in consensus, qualitatively and semi
      quantitatively [maximum standardized uptake value (SUVmax)]. Histopathology (if
      available) and clinical/imaging/biochemical follow-up (minimum of 6 months) were
      employed as the reference standard. RESULTS: (18)F-FDG PET/CT was interpreted as
      positive in 59 and negative in 33 patients. Local disease was seen in 5, nodal
      disease in 50 and distant metastasis in 22 patients. PET/CT was true positive in
      49, false positive in 10, true negative in 30 and false negative in 3 patients.
      (18)F-FDG PET/CT showed sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy of 94.2%, 75.0%, 83.0%, 90.9% and 85.8%
      overall; 90.0%, 74.0%, 72.0%, 90.9% and 80.8% in seminomatous GCT; and 96.8%,
      76.9%, 91.1%, 90.9% and 91.1% in non-seminomatous GCT, respectively. Difference
      in PET/CT accuracy for seminomatous and non-seminomatous GCTs was not significant
      (p = 0.263). PET/CT demonstrated disease in 13 patients with negative/equivocal
      conventional imaging findings and in 9 patients with normal tumour markers. No
      site- or histology-based difference was seen in SUVmax. CONCLUSION: (18)F-FDG
      PET/CT demonstrates high diagnostic accuracy for restaging patients with
      malignant GCTs. It has comparable diagnostic performance in both seminomatous and
      non-seminomatous malignant GCTs. ADVANCES IN KNOWLEDGE: The present article
      demonstrates high diagnostic accuracy of (18)F-FDG PET/CT for restaging both
      seminomatous and non-seminomatous malignant GCTs in a large patient population.

PMID- 24896201
TI  - Exploring the covariates of sport participation for health: an analysis of males
      and females in England.
AB  - Increasing sport participation has been identified as a key vehicle for achieving
      World Health Organisation guidelines for health-enhancing physical activity
      (HEPA). A policy challenge is to promote this changed behaviour. Making use of
      the Active People Survey, a zero-inflated ordered probit model is used to
      identify the covariates of sport participation for males and females with respect
      to the related decisions to either participate in sport or not, and to
      participate at either lower or higher than desired intensity. To inform current
      policy emphases, the Active Places Survey is also used to examine the causal
      impact of facility provision on these behaviours. Results indicate that females
      are more likely to adopt less intensive activity even with time available.
      Families could place most constraints on females, but also reduce the intensity
      of male participation. Education has a greater association with higher intensity
      female activity. The largest effects are identified for sport club membership and
      facility satisfaction. Both of these affect male intensity of activity most. The
      main policy challenges facing sport in contributing to HEPA are shown to involve
      retaining male intensity of participation when ageing and encouraging greater
      female intensity of participation, with more appropriate matching of facilities.

PMID- 24896202
TI  - Spaces for learning--A neglected area in curriculum change and strategic
      educational leadership.

PMID- 24896203
TI  - Somatostatin receptor-based PET/CT of intracranial tumors: a potential area of
      application for 68 Ga-DOTA peptides?
AB  - OBJECTIVE: Similar to neuroendocrine tumors (NETs) at other sites, a wide array
      of intracranial tumors also express somatostatin receptors (SSTRs). This
      expression can be exploited for both imaging and therapy. The introduction of
      (68)Ga-labeled tetraazacyclododecanetetraacetic acid (DOTA)-peptide PET/CT has
      given new dimension to SSTR-based imaging because of its improved sensitivity and
      excellent spatial resolution. CONCLUSION: However, in contrast to
      gastropancreatic and bronchopulmonary NETs, limited literature is available
      regarding the use of (68)Ga-DOTA-peptide PET/CT in intracranial tumors. Here, we
      briefly review the available literature and highlight the potential role that
      (68)Ga-DOTA-peptide PET/CT can play in the management of intracranial tumors.

PMID- 24896205
TI  - Impairment of the face processing network in congenital prosopagnosia.
AB  - The goal of the current paper is to review recent findings concerning the neural
      basis of congenital prosopagnosia (CP), a lifelong impairment in face processing
      that occurs in the absence of explicit brain damage. As such, CP offers a unique
      model for exploring the psychological and neural bases of normal face processing.
      We start by providing background about face perception and representation, and
      then review behavioral evidence gleaned from individuals with CP. We then review
      recent functional and structural neural investigations which offer a
      comprehensive account of the mechanisms underlying CP and support a
      characterization of this impairment as a disconnection syndrome rather than as a
      syndrome related to focal brain malfunction. We end the paper by offering a
      general framework for CP which, we believe, best integrates the behavioral and
      neural findings, and offers a platform for generating hypotheses for future
      studies. There remain many open issues in our understanding of CP and, to address
      these unanswered questions, we lay out several future research directions and
      testable hypotheses for further investigation. 

PMID- 24896204
TI  - Bridging between transplantation therapy and neurotrophic factors in Parkinson's
      disease.
AB  - Parkinson's disease (PD) represents a challenging condition where different
      therapeutic options have evolved over the course of the last 50 years. The
      potential for therapeutic use of cell transplantation for cell replacement or for
      gene delivery of neurotrophic factors has received a great deal of attention.
      Currently, all available treatment options are directed towards the amelioration
      of symptoms. A greater understanding of the distinctive pathology underlying PD
      might offer some novel therapeutic approaches. Transplantation of embryonic
      ventral mesencephalon (VM) dopaminergic neurons has shown promise in animal
      studies, but similar transplant procedures have shown limited success in clinical
      trials. One important issue may be the site of transplantation. Previous studies
      have transplanted VM into the striatum, which is the target of these neurons.
      With increased understanding of growth and guidance molecule effecting
      dopaminergic neurons, it may be feasible to place transplants in the damaged
      substantia nigra and direct the growth of axons into target regions to
      reconstruction of midbrain dopamine (DA) circuitry. Our established and on-going
      understanding of the molecular cues which support directed growth of DA neurons
      form an important basis for the refinement and optimization of VM grafting
      procedures, and also the development of new procedures based on the use of stem
      cells. In this review, we discuss transplantation therapy and how selective
      guidance molecules could be used to reconstruction of nigrostriatal circuit. 

PMID- 24896206
TI  - Understanding face perception by means of prosopagnosia and neuroimaging.
AB  - Understanding the human neuro-anatomy of face recognition is a long-standing goal
      of Cognitive Neuroscience. Studies of patients with face recognition impairment
      following brain damage (i.e., acquired prosopagnosia) have revealed the
      specificity of face recognition, the importance and nature of holistic/configural
      perception of individual faces, and the distribution of this function in the
      ventral occipito-temporal (VOT) cortex, with a right hemispheric dominance. Yet,
      neuroimaging studies in this field have essentially focused on a single face
      selective area of the VOT and underestimated the right hemisphere superiority.
      Findings in these studies have also been taken as supporting a hierarchical view
      of face perception, according to which a face is decomposed into parts in early
      face-selective areas, these parts being subsequently integrated into a whole
      representation in higher-order areas. This review takes a historical and current
      perspective on the study of acquired prosopagnosia and neuroimaging that
      challenges this latter view. It argues for a combination of these methods, an
      approach suggesting a coarse-to-fine emergence of the holistic face percept in a
      non-hierarchical network of cortical face-selective areas. 

PMID- 24896207
TI  - Involvement of PARPs in cell death.
AB  - Poly(ADP-ribosylation), an NAD dependent reaction culminating in the formation of
      ADP-ribose monomers, and their following polymerization, is activated as an
      emergency process in crucial situations such as DNA damage and cellular stress;
      due to this crucial function, the modulation of poly(ADP-ribosylation) during
      cell death has been investigated. This review will describe the properties of
      poly(ADP-ribose) as a signalling molecule in different paradigms of cell death,
      i.e.apoptosis, parthanatos, necroptosis and autophagy. 

PMID- 24896208
TI  - The pathophysiology of smoking during pregnancy: a systems biology approach.
AB  - This article focuses on a systems biology approach to studying the
      pathophysiology of cigarette smoking during pregnancy. Particular emphasis is
      given to the damaging role of oxidative stress. Cigarette smoking exerts multiple
      adverse affects but abundant evidence, mostly in adults, suggests that oxidative
      stress and free radical damage is a major pathophysiological factor. Smoking
      during pregnancy is known to contribute to numerous poor birth outcomes, such as
      low birth weight, preterm birth as well as life-long health and developmental
      problems. It is clinically important to know the separate contributions that
      cigarette derived-nicotine and smoking-induced free oxidative stress make to
      these poor outcomes. Surprisingly, the extent to which smoking dependent
      oxidative stress contributes to these poor outcomes is not well studied but the
      application of redox proteomics should be useful. Considerable biochemical
      evidence suggests that antioxidants, such as tocopherols and ascorbate, could be
      useful in minimizing oxidative stress induced pathology to the developing fetus
      in those women who, despite medical advice, continue to smoke. Nevertheless, this
      suggestion has yet to be tested in well-designed clinical studies. 

PMID- 24896209
TI  - Pharmacoresistant epilepsy and nanotechnology.
AB  - Epilepsy is one of the most common chronic neurological disorders. Furthermore,
      it is associated to diminished health-related quality of life and is thus
      considered a major public health problem. In spite of the large number of
      available and ongoing development of several new antiepileptic drugs (AEDs), a
      high percentage of patients with epilepsy (35-40%) are resistant to
      pharmacotherapy. A hypothesis to explain pharmacoresistance in epilepsy suggests
      that overexpression of multidrug resistance proteins, such as P-glycoprotein, on
      the endothelium of the blood brain barrier represents a challenge for effective
      AED delivery and concentration levels in the brain. Proven therapeutic strategies
      to control pharmacoresistant epilepsy include epilepsy surgery and
      neuromodulation. Unfortunately, not all patients are candidates for these
      therapies. Nanotechnology represents an attractive strategy to overcome the
      limited brain access of AEDs in patients with pharmacoresistant epilepsy. This
      manuscript presents a review of evidences supporting this idea. 

PMID- 24896210
TI  - Role of agmatine in neurodegenerative diseases and epilepsy.
AB  - Agmatine, a cationic polyamine synthesized after decarboxylation of L-arginine by
      the enzyme arginine decarboxylase, is an endogenous neuromodulator that emerges
      as a potential agent to manage diverse central nervous system (CNS) disorders.
      Consistent with its neuromodulatory and neuroprotective properties, there is
      increasing number of preclinical studies demonstrating the beneficial effects of
      exogenous agmatine administration on depression, anxiety, hypoxic ischemia,
      nociception, morphine tolerance, memory, Parkinson's disease, Alzheimer's
      disease, traumatic brain injury related alterations/disorders and epilepsy. The
      aim of this review is to summarize the knowledge about the effects of agmatine in
      CNS and point out its potential as new pharmacological treatment for diverse
      neurological and neurodegenerative diseases. Moreover, some molecular mechanisms
      underlying the neuroprotective effects of agmatine will be discussed. 

PMID- 24896211
TI  - Brain MRI in Parkinson's disease.
AB  - In this review article, conventional brain MRI and advanced MRI techniques in
      Parkinson's disease (PD) are discussed, with emphasis on clinical relevance.
      Conventional brain MRI sequences generally demonstrate limited abnormalities
      specific for PD and in clinical practice brain MRI is mainly used to exclude
      other pathology. Possibly, brain MRI at higher magnetic field strengths could
      provide new diagnostic markers. In recent years, new imaging techniques such as
      susceptibility weighted imaging (SWI), diffusion (tensor) MRI, magnetization
      transfer imaging (MTI), and functional MRI (f-MRI) have been applied to patient
      cohorts with PD to improve understanding of pathophysiologic changes, including
      functional connectivity. These advanced MRI techniques hold promise to provide
      additional diagnostic markers for early stage PD, as demonstrated by diffusional
      changes in the orbital-frontal region in the pre-motor phase of PD. Whether these
      advanced MRI techniques provide new diagnostic markers for early stage PD,
      remains a debate. Standardization of scanning protocols and post-processing
      methods, and validation of diagnostic criteria is crucial for these advanced MRI
      techniques. For this, well designed prospective clinical cohort studies are
      needed. 

PMID- 24896212
TI  - Oral lichen planus: a narrative review.
AB  - Oral Lichen Planus (OLP) is a common disease of unknown aetiology affecting oral
      mucosae by T-cell mediated chronic inflammation. OLP diagnosis is made by
      evaluating both clinical and histological criteria. Pharmacological treatment is
      useful in symptomatic cases. Life-long clinical follow-up is essential, due to
      low-risk of malignant transformation. In vivo Reflectance Confocal Microscopy
      (RCM) offers a real-time virtual biopsy of the being tissues and does not require
      surgical excision nor histopathological processing. RCM was used to capture OLP
      lesions in order to clinically differentiate them from other clinical entities. 

PMID- 24896214
TI  - Antiepileptic drugs: Energy-consuming processes governing drug disposition.
AB  - Diffusion is not the main process by which drugs are disposed throughout the
      body. Translational movements of solutes given by different energy-consuming
      mechanisms are required in order to dispose them efficiently. Membrane
      transportation and cardiac output distribution are two effective processes to
      move the molecules among different body sites. Gastrointestinal-blood cycling
      constitutes a supplementary way to regulate the distribution of molecules between
      the non-hepatic organs and the liver. Any change in the relative supply of drug
      molecules among eliminating organs could modify their clearance from the body.
      Either the nonlinear phenytoin (PHT) pharmacokinetic response or the influence
      that carbamazepine (CBZ) exerts on PHT exposure could be explained throughout
      their efflux transporter inducer abilities. Cardiac output distribution
      difference between the individuals might also explain the dual CBZ-over-PHT
      interaction response. Finally, valproic acid (VPA) pharmacokinetics can be
      understood by adding to these mechanisms of transportation its ability to cross
      the mitochondrial membrane of the hepatocyte. 

PMID- 24896215
TI  - A robust bayesian estimate of the concordance correlation coefficient.
AB  - A need for assessment of agreement arises in many situations including
      statistical biomarker qualification or assay or method validation. Concordance
      correlation coefficient (CCC) is one of the most popular scaled indices reported
      in evaluation of agreement. Robust methods for CCC estimation currently present
      an important statistical challenge. Here, we propose a novel Bayesian method of
      robust estimation of CCC based on multivariate Student's t-distribution and
      compare it with its alternatives. Furthermore, we extend the method to
      practically relevant settings, enabling incorporation of confounding covariates
      and replications. The superiority of the new approach is demonstrated using
      simulation as well as real datasets from biomarker application in
      electroencephalography (EEG). This biomarker is relevant in neuroscience for
      development of treatments for insomnia. 

PMID- 24896213
TI  - Genetic polymorphisms associated with antiepileptic metabolism.
AB  - Several factors, including pharmacogenetics, contribute to inter-individual
      variability in drug response. Many antiepileptic drugs (AEDs) are metabolized by
      a variety of enzymatic reactions, and the cytochrome P450 (CYP) family has
      attracted considerable attention. Some of the CYPs exist as genetic (allelic)
      variants, which may also affect the plasma concentrations or drug exposure.
      Regarding the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of
      particular interest. There have been recent advances in discovering factors such
      as these, especially those underlying the risk of medication toxicity. This
      review summarizes the evidence about whether such polymorphisms affect the
      clinical action of AEDs to facilitate future studies on the pharmacogenetics of
      epilepsy. We performed Key Words searches in the public databases PubMed,
      Medscape, and Rxlisty, Pharm GKB for genetic polymorphisms and the NCBI website
      for the nomenclature of alleles of CYP450, finding that CYP2D6, CYP2C9, CYP3A4,
      and CYP2D19 were involved in the metabolism of most antiepileptic drugs, given
      the allele frequency in the population and the associated variability in the
      clinical response. 

PMID- 24896216
TI  - Biotemplated inorganic nanostructures: supramolecular directed nanosystems of
      semiconductor(s)/metal(s) mediated by nucleic acids and their properties.

PMID- 24896217
TI  - In vitro toxicological assessment of iron oxide, aluminium oxide and copper
      nanoparticles in prokaryotic and eukaryotic cell types.
AB  - Metallic nanoparticles (NPs) have a variety of applications in different
      industries including pharmaceutical industry where these NPs are used mainly for
      image analysis and drug delivery. The increasing interest in nanotechnology is
      largely associated with undefined risks to the human health and to the
      environment. Therefore, in the present study cytotoxic and genotoxic effects of
      iron oxide, aluminium oxide and copper nanoparticles were evaluated using most
      commonly used assays i.e. Ames assay, in vitro cytotoxicity assay, micronucleus
      assay and comet assay. Cytotoxicity to bacterial cells was assessed in terms of
      colony forming units by using Escherichia coli (gram negative) and Bacillus
      subtilis (gram positive). Ames assay was carried out using two bacterial strains
      of Salmonella typhimurium TA98 and TA100. Genotoxicity of these NPs was evaluated
      following exposure to monkey kidney cell line, CHS-20. No cytotoxic and genotoxic
      effects were observed for iron oxide, and aluminium oxide NPs. Copper NPs were
      found mutagenic in TA98 and in TA100 and also found cytotoxic in dose dependent
      manner. Copper NPs induced significant (p < 0.01) increase in number of
      binucleated cells with micronuclei (96.6 +/- 5.40) at the highest concentration
      (25 ug/mL). Copper NPs also induced DNA strand breaks at 10 ug/mL and oxidative
      DNA damage at 5 and 10 ug/mL. We consider these findings very useful in
      evaluating the genotoxic potential of NPs especially because of their increasing
      applications in human health and environment with limited knowledge of their
      toxicity and genotoxicity. 

PMID- 24896218
TI  - Pre-hospital aspiration is associated with increased pulmonary complications.
AB  - BACKGROUND: Rates of ventilator-associated pneumonia (VAP) are highest among
      patients intubated on an emergency basis following trauma. We reported previously
      a retrospective analysis demonstrating an association between subjective
      aspiration and VAP after pre-hospital intubation. We hypothesize that by
      directing paramedics to note features of aspiration at intubation, we will
      confirm prospectively the association between pre-hospital aspiration and
      subsequent pneumonia in trauma patients. METHODS: Paramedics collected data
      regarding aspiration at the time of intubation. All intubated patients admitted
      to a level 1 trauma center intensive care unit (ICU) were included. Data
      comprised a clinical impression of pre-hospital aspiration, as well as the
      presence and timing of blood and emesis in the airway. Injury severity, co
      morbidities, and outcomes were collected from the trauma registry. Healthcare
      associated pneumonia (HAP) was identified by medical record review of both
      bronchoalveolar lavage culture results and discharge diagnosis. Descriptive
      statistics and univariate analysis of outcomes by aspiration status, as well as
      covariable adjustment using propensity scores, were performed. RESULTS: Of the
      228 patients, 89 (39%) were determined by paramedics to have aspirated. The
      majority of those who aspirated (84 [94%]) did so prior to intubation. Patients
      who aspirated had higher Injury Severity Scores than those who did not aspirate
      (25.0 +/- 1.7 vs. 21.9 +/- 1.5 points; p=0.04) and lower preintubation Glasgow
      Coma Scale scores (8.2 +/- 0.50 vs. 9.6 +/- 0.40; p=0.02). Of the 89 patients who
      aspirated around the time of intubation, 14 (16%) developed HAP vs. five (3.6%)
      of those who did not aspirate (p<0.01). We observed non-significant increases in
      mortality rate, ICU length of stay (LOS) and duration of mechanical ventilation
      after aspiration (deaths: 21 [23.6%] vs. 23 [16.6%]; p=0.19; ICU LOS: 5.3 +/- 0.9
      vs. 4.1 +/- 0.5 days; p=0.13; duration of mechanical ventilation: 5.3 +/- 1.2 vs.
      3.2 +/- 0.5 days; p=0.10). CONCLUSIONS: Aspiration prior to intubation was
      reported commonly by paramedics and was associated with a higher risk of HAP.

PMID- 24896219
TI  - Synchronization in autonomous mercury beating heart systems.
AB  - The ability of the mercury beating heart (MBH) system to exhibit sustained
      mechanical and electrochemical activities simultaneously without any external
      agent (fluctuating or constant), has attracted researchers for decades. The
      interplay of these activities could mimic the biological phenomena such as a
      pulsating heart that occurs due to the coupled tissues exhibiting mechanical as
      well as electrical dynamics. In the present work, we have studied experimentally
      the dynamics of electrically coupled two and three autonomous MBH systems. A
      dynamical triangular (heart) shape, in the traditional watch glass geometry, has
      been chosen for the experiments. It is found that the redox potentials
      (electrical behavior) of the quasi-identical (due to the inherent heterogeneities
      in the setup) MBH systems get synchronized at the intermediate coupling strengths
      whereas coherence in their mechanical activities occur only at large coupling
      strengths. To the best of our knowledge, this synchronization phenomenon
      involving two distinct activities (electrical and mechanical) and different
      coupling thresholds has not been reported, so far. The coherent mechanical
      activities means the simultaneous occurrence of compressions and expansions in
      the coupled Hg drops, which are shown using snapshots. In addition to this, the
      redox time series have also been provided to demonstrate the synchronization in
      the electrical behavior of MBH systems. Moreover, a mathematical framework
      considering only electrical and mechanical components of the MBH systems is
      presented to validate the experimental findings that the strong synchrony in the
      redox potentials of the MBH systems is a prerequisite for the synchrony in their
      mechanical activities. 

PMID- 24896221
TI  - Proposed data model for the next version of the synthetic biology open language.
AB  - While the first version of the Synthetic Biology Open Language (SBOL) has been
      adopted by several academic and commercial genetic design automation (GDA)
      software tools, it only covers a limited number of the requirements for a
      standardized exchange format for synthetic biology. In particular, SBOL Version
      1.1 is capable of representing DNA components and their hierarchical composition
      via sequence annotations. This proposal revises SBOL Version 1.1, enabling the
      representation of a wider range of components with and without sequences,
      including RNA components, protein components, small molecules, and molecular
      complexes. It also introduces modules to instantiate groups of components on the
      basis of their shared function and assert molecular interactions between
      components. By increasing the range of structural and functional descriptions in
      SBOL and allowing for their composition, the proposed improvements enable SBOL to
      represent and facilitate the exchange of a broader class of genetic designs. 

PMID- 24896220
TI  - Novel targeted therapies for the treatment of penile cancer.
AB  - INTRODUCTION: The treatment of penile cancer has changed over the past decade in
      that it was primarily a surgically managed disease and those with locally
      advanced or metastatic disease uniformly had a very poor prognosis. However, with
      the use of better traditional systemic chemotherapeutic agents in the neoadjuvant
      and adjuvant settings, the disease-specific survival and general outlook has
      improved. However, there is still a large group of patients who will progress
      even while on systemic therapy. It is in those patients where the application of
      targeted therapies has been investigated with some experiencing partial or even
      complete responses. With the improvement seen in patients with chemotherapy
      refractory disease, the application of novel targeted agents in the neoadjuvant
      setting may have a resultant positive impact on patient survival. AREAS COVERED:
      This review includes research pertaining to targeted therapies, biomarkers and
      signaling pathways involved with penile cancer. The article was based on a
      literature search using the keywords 'penile cancer' and 'targeted therapies'.
      EXPERT OPINION: Penile cancer at the advanced stages of the disease has a high
      mortality. The utilization of novel targeted therapies in these situations is
      warranted in combination with, or sequentially with, traditional cytotoxic
      chemotherapy to improve the patient survival rate. Personalized therapy is nearly
      here for penile cancer and should be made real within the next decade.

PMID- 24896223
TI  - In silico identification and biological evaluation of novel selective
      serum/glucocorticoid-inducible kinase 1 inhibitors based on the pyrazolo
      pyrimidine scaffold.
AB  - The serum/glucocorticoid-inducible kinase 1 (Sgk1) has demonstrated antiapoptotic
      function and the capability to regulate cell survival, proliferation, and
      differentiation. A pivotal role of Sgk1 in carcinogenesis and in resistance to
      anticancer therapy has been suggested. With the aim of identifying new Sgk1
      modulators, 322 pyrazolo-pyrimidine derivatives have been virtually screened with
      respect to a crystallographic model of Sgk1. The top five ranked compounds have
      been evaluated demonstrating Sgk1 inhibition in vitro and selectivity compared to
      RAC-alpha serine/threonine-protein kinase (Akt1). 

PMID- 24896222
TI  - Sensitivity of the valence structure in diruthenium complexes as a function of
      terminal and bridging ligands.
AB  - The compounds [(acac)2Ru(III)(MU-H2L(2-))Ru(III)(acac)2] (rac, 1, and meso, 1')
      and [(bpy)2Ru(II)(MU-H2L(*-))Ru(II)(bpy)2](ClO4)3 (meso, [2](ClO4)3) have been
      structurally, magnetically, spectroelectrochemically, and computationally
      characterized (acac(-) = acetylacetonate, bpy = 2,2'-bipyridine, and H4L = 1,4
      diamino-9,10-anthraquinone). The N,O;N',O'-coordinated MU-H2L(n-) forms two beta
      ketiminato-type chelate rings, and 1 or 1' are connected via NH...O hydrogen
      bridges in the crystals. 1 exhibits a complex magnetic behavior, while [2](ClO4)3
      is a radical species with mixed ligand/metal-based spin. The combination of redox
      noninnocent bridge (H2L(0) -> -> -> ->H2L(4-)) and {(acac)2Ru(II)} -> 
      >{(acac)2Ru(IV)} or {(bpy)2Ru(II)} -> {(bpy)2Ru(III)} in 1/1' or 2 generates
      alternatives regarding the oxidation state formulations for the accessible redox
      states (1(n) and 2(n)), which have been assessed by UV-vis-NIR, EPR, and DFT/TD
      DFT calculations. The experimental and theoretical studies suggest variable
      mixing of the frontier orbitals of the metals and the bridge, leading to the
      following most appropriate oxidation state combinations: [(acac)2Ru(III)(MU-H2L(*
      ))Ru(III)(acac)2](+) (1(+)) -> [(acac)2Ru(III)(MU-H2L(2-))Ru(III)(acac)2] (1) ->
      [(acac)2Ru(III)(MU-H2L(*3-))Ru(III)(acac)2](-)/[(acac)2Ru(III)(MU-H2L(2
      ))Ru(II)(acac)2](-) (1(-)) -> [(acac)2Ru(III)(MU-H2L(4-))Ru(III)(acac)2](2
      )/[(acac)2Ru(II)(MU-H2L(2-))Ru(II)(acac)2](2-) (1(2-)) and [(bpy)2Ru(III)(MU
      H2L(*-))Ru(II)(bpy)2](4+) (2(4+)) -> [(bpy)2Ru(II)(MU-H2L(*
      ))Ru(II)(bpy)2](3+)/[(bpy)2Ru(II)(MU-H2L(2-))Ru(III)(bpy)2](3+) (2(3+)) ->
      [(bpy)2Ru(II)(MU-H2L(2-))Ru(II)(bpy)2](2+) (2(2+)). The favoring of Ru(III) by
      sigma-donating acac(-) and of Ru(II) by the pi-accepting bpy coligands shifts the
      conceivable valence alternatives accordingly. Similarly, the introduction of the
      NH donor function in H2L(n) as compared to O causes a cathodic shift of redox
      potentials with corresponding consequences for the valence structure. 

PMID- 24896224
TI  - Thermodynamic analysis of protein folding and stability using a tryptophan
      modification protocol.
AB  - Described here is the development of a mass spectrometry-based covalent labeling
      protocol that utilizes the reaction of dimethyl(2-hydroxy-5-nitrobenzyl)sulfonium
      bromide (HNSB) with tryptophan (Trp) residues to measure protein folding free
      energies (DeltaG(f) values). In the protocol, the chemical denaturant dependence
      of the rate at which globally protected Trp residues in a protein react with HNSB
      is evaluated using either a matrix assisted laser desorption ionization time-of
      flight analysis of the intact protein or a quantitative, bottom-up proteomics
      analysis using isobaric mass tags. In the proof-of-principle studies performed
      here, the protocol yielded accurate DeltaG(f) values for the two-state folding
      proteins, lysozyme and cytochrome c. The protocol also yielded an accurate
      measure of the dissociation constant (K(d) value) for the binding of N,N',N"
      triacetylchitotriose to lysozyme, and it successfully detected the binding of
      brinzolamide to BCA II, a non-two-state folding protein. The HNSB protocol can be
      used in combination with SPROX (stability of proteins from rates of oxidation), a
      previously reported technique that exploits the hydrogen peroxide oxidation of
      methionine (Met) residues in proteins to make DeltaG(f) value measurements.
      Incorporating the HNSB protocol into SPROX increased the peptide and protein
      coverage in proteome-wide SPROX experiments by 50% and 25%, respectively. As part
      of this work, the precision of proteome-wide DeltaG(f) value measurements using
      the combined HNSB and SPROX protocol is also evaluated.

PMID- 24896225
TI  - Surface-plasmon-mediated programmable optical nanofabrication of an oriented
      silver nanoplate.
AB  - We report polarized femtosecond laser-light-mediated growth and programmable
      assembly of photoreduced silver nanoparticles into triply hierarchical
      micropatterns. Formation of erected arrays of nanoplates with a thickness as
      small as lambda/27 (lambda, the writing laser wavelength) level is demonstrated.
      The growth mechanism of nanoplates has been clarified: (i) the excited surface
      plasmons enhance the local electric field and lead to spatially selective growth
      of silver atoms at the opposite ends of dipoles induced on early created silver
      seeds; (ii) the optical attractive force overcomes electrostatic repulsion in the
      enhanced local electric field to assemble the silver nanoparticles directly. The
      triply hierarchical micropattern shape and location, the nanoplate orientation,
      and thickness are all attained in controlled fashion.

PMID- 24896227
TI  - Tunable band gap and doping type in silicene by surface adsorption: towards
      tunneling transistors.
AB  - By using first-principles calculations, we predict that a sizable band gap can be
      opened at the Dirac point of silicene without degrading silicene's electronic
      properties with n-type doping by Cu, Ag, and Au adsorption, p-type doping by Ir
      adsorption, and neutral doping by Pt adsorption. A silicene p-i-n tunneling field
      effect transistor (TFET) model is designed by the adsorption of different
      transition metal atoms on different regions of silicene. Quantum transport
      simulations demonstrate that silicene TFETs have an on-off ratio of 10(3), a
      small sub-threshold swing of 77 mV dec(-1), and a large on-state current of over
      1 mA MUm(-1) under a supply voltage of about 1.7 V. 

PMID- 24896226
TI  - Mechanistic insight with HBCH2CoA as a probe to polyhydroxybutyrate (PHB)
      synthases.
AB  - Polyhydroxybutyrate (PHB) synthases catalyze the polymerization of 3-(R)
      hydroxybutyrate coenzyme A (HBCoA) to produce polyoxoesters of 1-2 MDa. A
      substrate analogue HBCH2CoA, in which the S in HBCoA is replaced with a CH2
      group, was synthesized in 13 steps using a chemoenzymatic approach in a 7.5%
      overall yield. Kinetic studies reveal it is a competitive inhibitor of a class I
      and a class III PHB synthases, with Kis of 40 and 14 MUM, respectively. To probe
      the elongation steps of the polymerization, HBCH2CoA was incubated with a
      synthase acylated with a [(3)H]-saturated trimer-CoA ([(3)H]-sTCoA). The products
      of the reaction were shown to be the methylene analogue of [(3)H]-sTCoA ([(3)H]
      sT-CH2-CoA), saturated dimer-([(3)H]-sD-CO2H), and trimer-acid ([(3)H]-sT-CO2H),
      distinct from the expected methylene analogue of [(3)H]-saturated tetramer-CoA
      ([(3)H]-sTet-CH2-CoA). Detection of [(3)H]-sT-CH2-CoA and its slow rate of
      formation suggest that HBCH2CoA may be reporting on the termination and repriming
      process of the synthases, rather than elongation. 

PMID- 24896228
TI  - Rapid profiling of phenolic compounds of green and fermented Bergenia crassifolia
      L. leaves by UPLC-DAD-QqQ-MS and HPLC-DAD-ESI-QTOF-MS.
AB  - Bergenia crassifolia L., Saxifragaceae, is an evergreen perennial plant known in
      traditional medicine of Russia, Mongolia and China. Polyphenols are responsible
      for the number of pharmacological effects of Bergenia. UPLC-DAD-QqQ-MS and LC-DAD
      ESI-QTOF-MS were used for the rapid profiling of phenolic compounds, mainly
      hydrolysable tannins. Green leaves consisted of 55% ellagitannins, 29% gallic
      acid derivatives and 11% flavonoids, with the remaining gallic acid, arbutin,
      bergenin and caffeoyl quinic acid. In fermented leaves, 31% of gallic acid was
      found, followed with 28% ellagitannins, 18% gallic acid derivatives and 18%
      flavonoids, with the remaining caffeoyl quinic acid, bergenin and arbutin.
      Tellimagrandin I, pedunculagin, caffeoyl quinic acid, monogalloyl quinic acid, 1
      O-galloylglucose and 1,2,6-tri-O-galloylglucose were identified for the very
      first time. 

PMID- 24896229
TI  - Pyrimidine-based compounds modulate CXCR2-mediated signaling and receptor
      turnover.
AB  - Chemokine receptor CXCR2 is expressed on various immune cells and is essential
      for neutrophil recruitment and angiogenesis at sites of acute and chronic
      inflammation caused by tissue injury or infection. Because of its role in
      inflammation, it has been implicated in a number of immune-mediated inflammatory
      diseases such as psoriasis, arthritis, COPD, cystic fibrosis, asthma, and various
      types of cancer. CXCR2 and its ligands are up-regulated in cancer cells as well
      as the tumor microenvironment, promoting tumor growth, angiogenesis, and
      invasiveness. Although pharmaceutical companies have pursued the development of
      CXCR2-specific small-molecule inhibitors as anti-inflammatory agents within the
      last decades, there are currently no clinically approved CXCR2 inhibitors. Using
      a high-throughput, cell-based assay specific for CXCR2, we screened an in-house
      library of structurally diverse compounds and identified a class of pyrimidine
      based compounds that alter CXCR2-mediated second messenger signaling. Our lead
      compound, CX797, inhibited IL8-mediated cAMP signaling and receptor degradation
      while specifically up-regulating IL8-mediated beta-arrestin-2 recruitment. CX797
      also inhibited IL8-mediated cell migration. Mechanistic comparison of CX797 and a
      previously reported CXCR2 inhibitor, SB265610, show these two classes of
      compounds have a distinct mechanism of action on CXCR2. 

PMID- 24896230
TI  - Effect of noncovalent basal plane functionalization on the quantum capacitance in
      graphene.
AB  - The concentration-dependent density of states in graphene allows the capacitance
      in metal-oxide-graphene structures to be tunable with the carrier concentration.
      This feature allows graphene to act as a variable capacitor (varactor) that can
      be utilized for wireless sensing applications. Surface functionalization can be
      used to make graphene sensitive to a particular species. In this manuscript, the
      effect on the quantum capacitance of noncovalent basal plane functionalization
      using 1-pyrenebutanoic acid succimidyl ester and glucose oxidase is reported. It
      is found that functionalized samples tested in air have (1) a Dirac point similar
      to vacuum conditions, (2) increased maximum capacitance compared to vacuum but
      similar to air, (3) and quantum capacitance "tuning" that is greater than that in
      vacuum and ambient atmosphere. These trends are attributed to reduced surface
      doping and random potential fluctuations as a result of the surface
      functionalization due to the displacement of H2O on the graphene surface and
      intercalation of a stable H2O layer beneath graphene that increases the overall
      device capacitance. The results are important for future application of graphene
      as a platform for wireless chemical and biological sensors. 

PMID- 24896232
TI  - CNE Versus CEU: the confusing language of continuing education credit.

PMID- 24896233
TI  - The planning team-who belongs?
AB  - The composition of the planning team has a significant impact on the quality and
      outcome of continuing nursing education programs. It is imperative to identify
      the knowledge and skills needed to plan a specific program before choosing
      planning team members who have the required competencies.

PMID- 24896234
TI  - Developing leaders as systems thinkers-part III.
AB  - This article concludes a three-part series on developing leaders to function as
      systems thinkers. Part I differentiated between systematic and systems thinking
      and action, and part II elucidated competencies needed to develop and influence
      systems. The emphasis now shifts. Professional development educators are often
      expected to instruct individuals in multiple types of data collection, ranging
      from quality improvement to program evaluation metrics. The focus of this column
      is on collecting and using systems data.

PMID- 24896231
TI  - Glucose oxidase-catalyzed growth of gold nanoparticles enables quantitative
      detection of attomolar cancer biomarkers.
AB  - Ultrasensitive and quantitative detection of cancer biomarkers is an unmet
      challenge because of their ultralow concentrations in clinical samples. Although
      gold nanoparticle (AuNP)-based immunoassays offer high sensitivity, they were
      unable to quantitatively detect targets of interest most likely due to their very
      narrow linear ranges. This article describes a quantitative colorimetric
      immunoassay based on glucose oxidase (GOx)-catalyzed growth of 5 nm AuNPs that
      can detect cancer biomarkers from attomolar to picomolar levels. In addition, the
      limit of detection (LOD) of prostate-specific antigen (PSA) of this approach (93
      aM) exceeds that of commercial enzyme-linked immunosorbent assay (ELISA) (6.3 pM)
      by more than 4 orders of magnitude. The emergence of red or purple color based on
      enzyme-catalyzed growth of 5 nm AuNPs in the presence of target antigen is
      particularly suitable for point-of-care (POC) diagnostics in both resource-rich
      and resource-limited settings. 

PMID- 24896235
TI  - Learning to work in teams.
AB  - Optimum individual and team functioning can be progressed through organizational
      learning. Organizational learning is facilitated through positive team
      interactions. However, the process of shifting and shaping team behavior is not
      simple. This article offers strategies to help teams modify their interactions to
      better engage with and learn from each other. The effectiveness of these
      strategies in continuing staff development is evidenced in the development of
      highly functioning teams.

PMID- 24896237
TI  - Identification of those most likely to benefit from a low-glycaemic index dietary
      intervention in pregnancy.
AB  - The present study is a secondary analysis of the ROLO study, a randomised control
      trial of a low-glycaemic index (GI) diet in pregnancy to prevent the recurrence
      of fetal macrosomia. The objectives of the present study were to identify which
      women are most likely to respond to a low-GI dietary intervention in pregnancy
      with respect to three outcome measures: birth weight; maternal glucose
      intolerance; gestational weight gain (GWG). In early pregnancy, 372 women had
      their mid-upper arm circumference recorded and BMI calculated. Concentrations of
      glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. At
      delivery, infant birth weight was recorded and fetal glucose, C-peptide and
      leptin concentrations were measured in the cord blood. Women who benefited in
      terms of infant birth weight were shorter, with a lower education level. Those
      who maintained weight gain within the GWG guidelines were less overweight in both
      their first and second pregnancies, with no difference being observed in maternal
      height. Women who at 28 weeks of gestation developed glucose intolerance, despite
      the low-GI diet, had a higher BMI and higher glucose concentrations in early
      pregnancy with more insulin resistance. They also had significantly higher
      interval pregnancy weight gain. For each analysis, women who responded to the
      intervention had lower leptin concentrations in early pregnancy than those who
      did not. These findings suggest that the maternal metabolic environment in early
      pregnancy is important in determining later risks of excessive weight gain and
      metabolic disturbance, whereas birth weight is mediated more by genetic factors.
      It highlights key areas, which warrant further interrogation before future
      pregnancy intervention studies, in particular, maternal education level and inter
      pregnancy weight gain.

PMID- 24896238
TI  - Nutritional regulation of glucokinase: a cross-species story.
AB  - The glucokinase (GK) enzyme (EC 2.7.1.1.) is essential for the use of dietary
      glucose because it is the first enzyme to phosphorylate glucose in excess in
      different key tissues such as the pancreas and liver. The objective of the
      present review is not to fully describe the biochemical characteristics and the
      genetics of this enzyme but to detail its nutritional regulation in different
      vertebrates from fish to human. Indeed, the present review will describe the
      existence of the GK enzyme in different animal species that have naturally
      different levels of carbohydrate in their diets. Thus, some studies have been
      performed to analyse the nutritional regulation of the GK enzyme in humans and
      rodents (having high levels of dietary carbohydrates in their diets), in the
      chicken (moderate level of carbohydrates in its diet) and rainbow trout (no
      carbohydrate intake in its diet). All these data illustrate the nutritional
      importance of the GK enzyme irrespective of feeding habits, even in animals known
      to poorly use dietary carbohydrates (carnivorous species). 

PMID- 24896241
TI  - Linking immunity, epigenetics, and cancer in inflammatory bowel disease.
AB  - Most of what is known about the pathogenesis of inflammatory bowel disease (IBD)
      pertains to complex interplay between host genetics, immunity, and environmental
      factors. Epigenetic modifications play pivotal roles in intestinal immunity and
      mucosal homeostasis as well as mediating gene-environment interactions. In this
      article, we provide a historical account of epigenetic research either directly
      related or pertinent to the pathogenesis and management of IBD. We further
      collate emerging evidence supporting roles for epigenetic mechanisms in relevant
      aspects of IBD biology, including deregulated immunity, host-pathogen recognition
      and mucosal integrity. Finally, we highlight key epigenetic mechanisms that link
      chronic inflammation to specific IBD comorbidities, including colitis-associated
      cancer and discuss their potential utility as novel biomarkers or pharmacologic
      targets in IBD therapy.

PMID- 24896240
TI  - Histone deacetylase HDAC4 promotes gastric cancer SGC-7901 cells progression via
      p21 repression.
AB  - Gastric cancer (GC) is one of the leading causes of cancer death in the world.
      The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has
      been identified. However, its biological roles in the development of gastric
      cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and
      western blot were used to analyze the expression of HDAC4 in the clinical
      samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study
      functional effects in a proliferation, a colony formation, a adenosine 5'
      triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle,
      cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric
      cancer tissues and several gastric cancer cell lines. The proliferation, colony
      formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901
      cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to
      G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4
      was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21
      knockdown dramatically attenuated cell proliferation inhibition, cell cycle
      arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC
      7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression
      mediated through the repression of p21. Our results provide an experimental basis
      for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric
      cancer. 

PMID- 24896242
TI  - Hydrogen sulfide releasing aspirin, ACS14, attenuates high glucose-induced
      increased methylglyoxal and oxidative stress in cultured vascular smooth muscle
      cells.
AB  - Hydrogen sulfide is a gasotransmitter with vasodilatory and anti-inflammatory
      properties. Aspirin is an irreversible cyclooxygenase inhibitor anti-inflammatory
      drug. ACS14 is a novel synthetic hydrogen sulfide releasing aspirin which
      inhibits cyclooxygenase and has antioxidant effects. Methylglyoxal is a
      chemically active metabolite of glucose and fructose, and a major precursor of
      advanced glycation end products formation. Methylglyoxal is harmful when produced
      in excess. Plasma methylglyoxal levels are significantly elevated in diabetic
      patients. Our aim was to investigate the effects of ACS14 on methylglyoxal levels
      in cultured rat aortic vascular smooth muscle cells. We used cultured rat aortic
      vascular smooth muscle cells for the study. Methylglyoxal was measured by HPLC
      after derivatization, and nitrite+nitrate with an assay kit. Western blotting was
      used to determine NADPH oxidase 4 (NOX4) and inducible nitric oxide synthase
      (iNOS) protein expression. Dicholorofluorescein assay was used to measure
      oxidative stress. ACS14 significantly attenuated elevation of intracellular
      methylglyoxal levels caused by incubating cultured vascular smooth muscle cells
      with methylglyoxal (30 uM) and high glucose (25 mM). ACS14, but not aspirin,
      caused a significant attenuation of increase in nitrite+nitrate levels caused by
      methylglyoxal or high glucose. ACS14, aspirin, and sodium hydrogen sulfide (NaHS,
      a hydrogen sulfide donor), all attenuated the increase in oxidative stress caused
      by methylglyoxal and high glucose in cultured cells. ACS14 prevented the increase
      in NOX4 expression caused by incubating the cultured VSMCs with MG (30 uM).
      ACS14, aspirin and NaHS attenuated the increase in iNOS expression caused by high
      glucose (25 mM). In conclusion, ACS14 has the novel ability to attenuate an
      increase in methylglyoxal levels which in turn can reduce oxidative stress,
      decrease the formation of advanced glycation end products and prevent many of the
      known deleterious effects of elevated methylglyoxal. Thus, ACS14 has the
      potential to be especially beneficial for diabetic patients pending further in
      vivo studies.

PMID- 24896244
TI  - Cytotoxic aryltetralin lignans from fruits of Cleistanthus indochinensis.
AB  - Eight new aryltetralin lignans, cleisindosides A-F (1-6), picroburseranin (7),
      and 7-hydroxypicropolygamain (8), were isolated from the fruits of Cleistanthus
      indochinensis (Euphorbiaceae). The structures of the isolates were established on
      the basis of their one- and two-dimensional NMR spectral data, as well as their
      mass spectrometric data. Compound 7 was found to have potent cytotoxicity against
      oral epidermoid carcinoma cells with an IC50 value of 0.062 uM, whereas
      glycosylation to 3 (IC50 7.5 uM) and stereochemical changes to 8 (IC50 10.8 uM)
      led to marked decreases in biological activity. Thus, it was determined that the
      C-7 and C-8' positions are critical for the biological activity of the lignans
      from this plant.

PMID- 24896243
TI  - Modifiable risk factors for Alzheimer disease and subjective memory impairment
      across age groups.
AB  - INTRODUCTION: Previous research has identified modifiable risk factors for
      Alzheimer's disease (AD) in older adults. Research is limited on the potential
      link between these risk factors and subjective memory impairment (SMI), which may
      precede AD and other dementias. Examination of these potential relationships may
      help identify those at risk for AD at a stage when interventions may delay or
      prevent further memory problems. The objective of this study was to determine
      whether risk factors for AD are associated with SMI among different age groups.
      METHOD: Trained interviewers conducted daily telephone surveys (Gallup
      Healthways) of a representative community sample of 18,614 U.S. respondents,
      including 4,425 younger (age 18 to 39 years), 6,365 middle-aged (40 to 59 years),
      and 7,824 older (60 to 99 years) adults. The surveyors collected data on
      demographics, lifestyles, and medical information. Less education, smoking,
      hypertension, diabetes, less exercise, obesity and depression, and interactions
      among them, were examined for associations with SMI. Weighted logistic
      regressions and chi-square tests were used to calculate odds ratios and
      confidence intervals for SMI with each risk factor and pairwise interactions
      across age groups. RESULTS: Depression, less education, less exercise, and
      hypertension were significantly associated with SMI in all three age groups.
      Several interactions between risk factors were significant in younger and middle
      aged adults and influenced their associations with SMI. Frequency of SMI
      increased with age and number of risk factors. Odds of having SMI increased
      significantly with just having one risk factor. CONCLUSIONS: These results
      indicate that modifiable risk factors for AD are also associated with SMI,
      suggesting that these relationships occur in a broad range of ages and may be
      targeted to mitigate further memory problems. Whether modifying these risk
      factors reduces SMI and the eventual incidence of AD and other dementias later in
      life remains to be determined.

PMID- 24896245
TI  - Perinephric adipose tissue thickness in relation to blood pressure, plasma apelin
      and C-reactive protein levels in obese adolescents.
AB  - BACKGROUND: Visceral adiposity plays an important role in the pathogenesis of
      obesity related hypertension. Measurement of perinephric adipose tissue (PNAT)
      thickness has not been studied yet. We aimed to define the relation of PNAT with
      hypertension, and to investigate its correlations with apelin and C-reactive
      protein. METHODS: Sixty obese adolescents (33 females, 27 males) with a mean age
      of 14.0+/-0.8 years and 29 age-matched lean controls were recruited. Obese
      subjects were divided as hypertensive (Group 1) and normotensive (Group 2) using
      24-hour ambulatory blood pressure monitoring. PNAT was measured using
      ultrasonography bilaterally. RESULTS: PNAT thickness was found increased by 0.5
      mm for each point of increase in body mass index (BMI). Plasma apelin levels were
      significantly higher in Groups 1 and 2 than those in control group (P<0.001 and
      P=0.001, respectively). In Group 1 BMI, plasma insulin and cortisol levels were
      significantly higher. Apelin was positively correlated with BMI and PNAT (P<0.001
      for both), and negatively correlated with pubertal stage (rho=-0.313, P=0.003)
      and age (rho=-0.250; P=0.018). CONCLUSIONS: This is the first study showing
      direct correlation between PNAT and BMI and also between apelin and BMI in obese
      adolescents. Hypertension in adolescence is related to degree of obesity. While
      plasma apelin increases in obesity, it decreases with increasing age and pubertal
      stage.

PMID- 24896246
TI  - Desvenlafaxine may accelerate neuronal maturation in the dentate gyri of adult
      male rats.
AB  - Adult hippocampal neurogenesis has been linked to the effects of anti-depressant
      drugs on behavior in rodent models of depression. To explore this link further,
      we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI)
      venlafaxine impacted adult hippocampal neurogenesis differently than its primary
      active SNRI metabolite desvenlafaxine. Adult male Long Evans rats (n = 5-6 per
      group) were fed vehicle, venlafaxine (0.5 or 5 mg) or desvenlafaxine (0.5 or 5
      mg) twice daily for 16 days. Beginning the third day of drug treatment, the rats
      were given a daily bromodeoxyuridine (BrdU; 50 mg/kg) injection for 5 days to
      label dividing cells and then perfused 2 weeks after the first BrdU injection to
      confirm total new hippocampal cell numbers and their phenotypes. The high
      desvenlafaxine dose increased total new BrdU+ cell number and appeared to
      accelerate neuronal maturation because fewer BrdU+ cells expressed maturing
      neuronal phenotypes and more expressed mature neuronal phenotypes in the dentate
      gyri of these versus vehicle-treated rats. While net neurogenesis was not
      increased in the dentate gyri of rats treated with the high desvenlafaxine dose,
      significantly more mature neurons were detected. Our data expand the body of
      literature showing that antidepressants impact adult neurogenesis by stimulating
      NPC proliferation and perhaps the survival of neuronal progeny and by showing
      that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high
      nor low venlafaxine dose, may also accelerate neuronal maturation in the adult
      rat hippocampus. These data support the hypothesis that hippocampal neurogenesis
      may indeed serve as a biomarker of depression and the effects of antidepressant
      treatment, and may be informative for developing novel fast-acting antidepressant
      strategies.

PMID- 24896248
TI  - Cardiovascular risk assessment before and after kidney transplantation.
AB  - Cardiovascular disease (CVD) is the leading cause of death in dialysis patients
      and the most common cause of death and allograft loss among kidney transplant
      recipients. End-stage renal disease (ESRD) is associated with an increased
      incidence and prevalence of a wide range of CVDs including coronary artery
      disease, stroke, congestive heart failure, atrial fibrillation, sudden cardiac
      death, pulmonary hypertension, and valvular heart disease. CVD risk factors are
      very common in patients with ESRD, and most patients have multiple risk factors.
      Kidney transplantation is the treatment of choice for patients with ESRD, as a
      successful transplant improves longevity and quality of life, primarily by
      decreasing the incidence and severity of CVD. Correction of the uremic state and
      improved glomerular filtration rate seem to be the major mechanism of this
      benefit. Transplant candidates should undergo cardiovascular assessment, usually
      echocardiography and exercise stress testing, and may require formal cardiology
      consultation. Higher risk candidates, including those aged >50 years,
      hypertension, diabetes, established coronary artery disease or peripheral
      vascular disease, left ventricular hypertrophy, and dialysis duration >1 year,
      should have repeat cardiovascular assessment every 1-2 years. Transplant
      candidates and recipients should have individualized treatment for CVD and risk
      factors such as hypertension, diabetes, hyperlipidemia, and obesity. Special
      consideration should be given for statin therapy, as its use is associated with
      decreased cardiovascular death in dialysis and transplant patients. Prospective
      randomized, controlled trials are needed to determine the optimal approach to
      diagnosis and treat CVD in the transplant candidate and recipient population. 

PMID- 24896247
TI  - Vulnerability of homeless people in Tehran, Iran, to HIV, tuberculosis and viral
      hepatitis.
AB  - BACKGROUND: Homeless people are at risk of contracting communicable infectious
      diseases, as they indulge in risky behaviours and lifestyle. This study was
      conducted to determine the prevalence of the aforementioned infections and
      related risk behaviours among homeless people in Tehran. METHODS: In this study a
      convenience sample of 593 homeless individuals was studied. The ELISA method was
      used for the detection of HIV, HCV and HBV. Clinical symptoms, sputum cultures,
      acid fast bacilli smears, and chest X-rays were used to identify active pulmonary
      tuberculosis, and the Interferon Gamma Release Assay (IGRA) test was used to
      identify latent tuberculosis. RESULTS: The prevalence of HIV, HBV, HCV and latent
      tuberculosis was 3.4%, 2.6%, 23.3% and 46.7%, respectively. Active pulmonary
      tuberculosis was found in 7 persons (1.2%). Injection drug use was an independent
      risk factor for HIV, HCV and HBV infections. Older people had a higher proportion
      of Mycobacterium tuberculosis infection (OR: 2.6, 95%CI: 1.9, 3.7) and HCV
      positivity (OR: 1.7, 95% CI: 1.1, 2.5). CONCLUSION: Our findings highlighted that
      much more attention needs to be paid to the health of homeless people.

PMID- 24896250
TI  - Role of magnesium in cardiovascular diseases.
AB  - Magnesium, the fourth most abundant cation in the human body, is involved in
      several essential physiological, biochemical, and cellular processes regulating
      cardiovascular function. It plays a critical role in modulating vascular smooth
      muscle tone, endothelial cell function, and myocardial excitability and is thus
      central to the pathogenesis of several cardiovascular disorders such as
      hypertension, atherosclerosis, coronary artery disease, congestive heart failure,
      and cardiac arrhythmias. This review discusses the vasodilatory, anti
      inflammatory, anti-ischemic, and antiarrhythmic properties of magnesium and its
      current role in the prevention and treatment of cardiovascular disorders. 

PMID- 24896252
TI  - Development and validation of the Smartphone Addiction Inventory (SPAI).
AB  - OBJECTIVE: The aim of this study was to develop a self-administered scale based
      on the special features of smartphone. The reliability and validity of the
      Smartphone Addiction Inventory (SPAI) was demonstrated. METHODS: A total of 283
      participants were recruited from Dec. 2012 to Jul. 2013 to complete a set of
      questionnaires, including a 26-item SPAI modified from the Chinese Internet
      Addiction Scale and phantom vibration and ringing syndrome questionnaire. There
      were 260 males and 23 females, with ages 22.9 +/- 2.0 years. Exploratory factor
      analysis, internal-consistency test, test-retest, and correlation analysis were
      conducted to verify the reliability and validity of the SPAI. Correlations
      between each subscale and phantom vibration and ringing were also explored.
      RESULTS: Exploratory factor analysis yielded four factors: compulsive behavior,
      functional impairment, withdrawal and tolerance. Test-retest reliabilities
      (intraclass correlations  = 0.74-0.91) and internal consistency (Cronbach's alpha
      = 0.94) were all satisfactory. The four subscales had moderate to high
      correlations (0.56-0.78), but had no or very low correlation to phantom
      vibration/ringing syndrome. CONCLUSION: This study provides evidence that the
      SPAI is a valid and reliable, self-administered screening tool to investigate
      smartphone addiction. Phantom vibration and ringing might be independent entities
      of smartphone addiction.

PMID- 24896249
TI  - Is there a paradox in obesity?
AB  - In an industrialized society, the increase in obesity incidence has led to an
      increase in premature morbidity and mortality rates. There is a relationship
      between body mass index (BMI) and the increased incidence of hypertension,
      dyslipidemia, type 2 diabetes mellitus, and cardiovascular disease, an increase
      in mortality. However, obese individuals with these conditions may have better
      outcomes than their lean counterparts, thus the term "obesity paradox." Most
      studies supporting this paradox are cross-sectional and do not take into account
      the quantity or type of adiposity, the disease severity, and comorbidities.
      Although BMI is an indicator of the amount of body fat, it does not differentiate
      between adiposity types. Adipocytes that are highly functional have good fuel
      storage capacity are different from adipocytes found in visceral obesity, which
      are poorly functioning, laden with macrophages, and causing low-grade
      inflammation. Individuals with high BMI may be physically fit and have a lower
      mortality risk when compared with individuals with a lower BMI and poorly
      functioning adiposity. We review the complexity of adipose tissue and its
      location, function, metabolic implications, and role in cardiovascular morbidity
      and mortality. The terminology "obesity paradox" may reflect a lack of
      understanding of the complex pathophysiology of obesity and the association
      between adiposity and cardiovascular disease. 

PMID- 24896251
TI  - Household and school-level influences on smoking behavior among Korean
      adolescents: a multilevel analysis.
AB  - BACKGROUND: Trends in adolescent smoking rates in South Korea have not shown
      substantial progress due to a lack of effective anti-smoking interventions and
      policies in school settings. METHODS AND FINDINGS: We examined individual- and
      school-level determinants of adolescent smoking behavior (ever smoking, current
      smoking, and daily smoking) using the nationally representative fifth Korean
      Youth Risk Behavior Web-based Survey conducted in 2009. We found that students in
      coeducation schools or vocational high schools had greater risks of smoking for
      each type of smoking behavior than those in single-sex schools or general high
      schools, respectively even after controlling for individual-level factors. Higher
      family affluence and higher weekly allowances were associated with greater risks
      of ever smoking, current smoking and daily smoking even after controlling for
      parental education and other confounders. CONCLUSIONS: Whilst caution is required
      in interpreting results given the cross-sectional nature of the study, our
      findings suggest that in addition to raising the price of cigarettes, youth anti
      smoking interventions in South Korea may benefit from focusing on coeducation
      schools and vocational high schools.

PMID- 24896256
TI  - Energy costs of catfish space use as determined by biotelemetry.
AB  - Animals use dispersed resources within their home range (HR) during regular day
      to-day activities. The high-quality area intensively used by an individual, where
      critical resources are concentrated, has been designated as the core area (CA).
      This study aimed to describe how animals utilize energy in the HR and CA assuming
      that changes would occur according to the size of the used areas. We observed
      energetic costs of space use in the largest European freshwater predator catfish,
      Silurus glanis, using physiological sensors. Catfish consumed significantly more
      energy within the CA compared to the rest of the HR area. In addition, energetic
      costs of space use within a large area were lower. These results generally
      indicate that utilization of larger areas is related to less demanding
      activities, such as patrolling and searching for new resources and mates. In
      contrast, fish occurrence in small areas appears to be related to energetically
      demanding use of spatially limited resources. 

PMID- 24896257
TI  - Hepatitis E virus serosurvey among pet dogs and cats in several developed cities
      in China.
AB  - Infection by Hepatitis E virus (HEV), as a zoonotic disease virus, is well
      studied in pigs in China, but few studies in pets have been performed. This study
      was designed to characterize the prevalence of HEV infection among pet dogs and
      cats in major metropolitan areas of China. We conducted a seroepidemiological
      survey from 2012 to 2013 in 5 developed cities, Beijing, Shanghai, Canton,
      Shenzhen and Macao, by enzyme-linked immunosorbent assay (ELISA). The overall HEV
      seroprevalence in 658 dog and 191 cat serum samples was 21.12% and 6.28%,
      respectively. The analysis in dogs suggested that there were significant
      differences among cities, and the positive rate of HEV-specific antibody in all
      cities ranged from 6.06% (Shenzhen) to 29.34% (Beijing). Older pet cats have a
      high risk (OR, 10.25) for HEV seropositivity, but no strong relationship was
      observed between different genders and age groups. Additionally, it was revealed
      that stray dogs, omnivorous pet dogs and pet cats who share food, such as kitchen
      residue, with the general population would have a higher risk for HEV
      seropositivity. The odds ratios for these groups are 2.40, 2.83 and 5.39,
      respectively, compared with pet dogs and cats fed on commercial food. In this
      study, we first report that HEV is prevalent in pet dogs and cats in several
      large cities in China. Swill and kitchen residue may be a potential risk for HEV
      transmission from human to pets. As the sample size was relatively small in this
      study and may not be fully representative of China, further investigation is
      required to confirm the conclusions. 

PMID- 24896258
TI  - Mechanistic study of manganese-substituted glycerol dehydrogenase using a kinetic
      and thermodynamic analysis.
AB  - Mechanistic insights regarding the activity enhancement of dehydrogenase by metal
      ion substitution were investigated by a simple method using a kinetic and
      thermodynamic analysis. By profiling the binding energy of both the substrate and
      product, the metal ion's role in catalysis enhancement was revealed. Glycerol
      dehydrogenase (GDH) from Klebsiella pneumoniae sp., which demonstrated an
      improvement in activity by the substitution of a zinc ion with a manganese ion,
      was used as a model for the mechanistic study of metal ion substitution. A
      kinetic model based on an ordered Bi-Bi mechanism was proposed considering the
      noncompetitive product inhibition of dihydroxyacetone (DHA) and the competitive
      product inhibition of NADH. By obtaining preliminary kinetic parameters of
      substrate and product inhibition, the number of estimated parameters was reduced
      from 10 to 4 for a nonlinear regression-based kinetic parameter estimation. The
      simulated values of time-concentration curves fit the experimental values well,
      with an average relative error of 11.5% and 12.7% for Mn-GDH and GDH,
      respectively. A comparison of the binding energy of enzyme ternary complex for Mn
      GDH and GDH derived from kinetic parameters indicated that metal ion substitution
      accelerated the release of dioxyacetone. The metal ion's role in catalysis
      enhancement was explicated. 

PMID- 24896261
TI  - The devil's in the details.

PMID- 24896260
TI  - Reliability of different mark-recapture methods for population size estimation
      tested against reference population sizes constructed from field data.
AB  - Reliable estimates of population size are fundamental in many ecological studies
      and biodiversity conservation. Selecting appropriate methods to estimate
      abundance is often very difficult, especially if data are scarce. Most studies
      concerning the reliability of different estimators used simulation data based on
      assumptions about capture variability that do not necessarily reflect conditions
      in natural populations. Here, we used data from an intensively studied closed
      population of the arboreal gecko Gehyra variegata to construct reference
      population sizes for assessing twelve different population size estimators in
      terms of bias, precision, accuracy, and their 95%-confidence intervals. Two of
      the reference populations reflect natural biological entities, whereas the other
      reference populations reflect artificial subsets of the population. Since
      individual heterogeneity was assumed, we tested modifications of the Lincoln
      Petersen estimator, a set of models in programs MARK and CARE-2, and a truncated
      geometric distribution. Ranking of methods was similar across criteria. Models
      accounting for individual heterogeneity performed best in all assessment
      criteria. For populations from heterogeneous habitats without obvious covariates
      explaining individual heterogeneity, we recommend using the moment estimator or
      the interpolated jackknife estimator (both implemented in CAPTURE/MARK). If data
      for capture frequencies are substantial, we recommend the sample coverage or the
      estimating equation (both models implemented in CARE-2). Depending on the
      distribution of catchabilities, our proposed multiple Lincoln-Petersen and a
      truncated geometric distribution obtained comparably good results. The former
      usually resulted in a minimum population size and the latter can be recommended
      when there is a long tail of low capture probabilities. Models with covariates
      and mixture models performed poorly. Our approach identified suitable methods and
      extended options to evaluate the performance of mark-recapture population size
      estimators under field conditions, which is essential for selecting an
      appropriate method and obtaining reliable results in ecology and conservation
      biology, and thus for sound management. 

PMID- 24896262
TI  - Diving into data: quantifying efficiency by improving patient flow.

PMID- 24896259
TI  - Genome at juncture of early human migration: a systematic analysis of two whole
      genomes and thirteen exomes from Kuwaiti population subgroup of inferred Saudi
      Arabian tribe ancestry.
AB  - Population of the State of Kuwait is composed of three genetic subgroups of
      inferred Persian, Saudi Arabian tribe and Bedouin ancestry. The Saudi Arabian
      tribe subgroup traces its origin to the Najd region of Saudi Arabia. By
      sequencing two whole genomes and thirteen exomes from this subgroup at high
      coverage (>40X), we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs),
      515,802 indels and 39,762 structural variations. Of the identified variants,
      10,098 (8.3%) exomic SNPs, 139,923 (2.9%) non-exomic SNPs, 5,256 (54.3%) exomic
      indels, and 374,959 (74.08%) non-exomic indels are 'novel'. Up to 8,070 (79.9%)
      of the reported novel biallelic exomic SNPs are seen in low frequency (minor
      allele frequency <5%). We observe 5,462 known and 1,004 novel potentially
      deleterious nonsynonymous SNPs. Allele frequencies of common SNPs from the 15
      exomes is significantly correlated with those from genotype data of a larger
      cohort of 48 individuals (Pearson correlation coefficient, 0.91; p <2.2*10-16). A
      set of 2,485 SNPs show significantly different allele frequencies when compared
      to populations from other continents. Two notable variants having risk alleles in
      high frequencies in this subgroup are: a nonsynonymous deleterious SNP (rs2108622
      [19:g.15990431C>T] from CYP4F2 gene [MIM:*604426]) associated with warfarin
      dosage levels [MIM:#122700] required to elicit normal anticoagulant response; and
      a 3' UTR SNP (rs6151429 [22:g.51063477T>C]) from ARSA gene [MIM:*607574])
      associated with Metachromatic Leukodystrophy [MIM:#250100]. Hemoglobin Riyadh
      variant (identified for the first time in a Saudi Arabian woman) is observed in
      the exome data. The mitochondrial haplogroup profiles of the 15 individuals are
      consistent with the haplogroup diversity seen in Saudi Arabian natives, who are
      believed to have received substantial gene flow from Africa and eastern
      provenance. We present the first genome resource imperative for designing future
      genetic studies in Saudi Arabian tribe subgroup. The full-length genome sequences
      and the identified variants are available at ftp://dgr.dasmaninstitute.org and
      http://dgr.dasmaninstitute.org/DGR/gb.html. 

PMID- 24896263
TI  - Processing of kansui roots stir-baked with vinegar reduces kansui-induced
      hepatocyte cytotoxicity by decreasing the contents of toxic terpenoids and
      regulating the cell apoptosis pathway.
AB  - Euphorbia kansui is a Traditional Chinese Medicine widely used for the treatment
      of oedema, ascites and asthma. However, its serious hepatotoxicity hinders its
      safe clinical application. The process of stir-baking with vinegar is regularly
      used to reduce the toxicity of kansui. Up till now, the exact mechanism of the
      reduction in hepatotoxicity of kansui stir-baked with vinegar has been poorly
      defined. In this study, decreased  contents of five diterpene and one triterpene
      in kansui (GS-1) after stir-baking with vinegar (GS-2) was investigated by UPLC
      QTOF/MS. Flow cytometry and Hoechst staining were used to show that the stir
      baking with vinegar process reduces kansui-induced cell apoptosis. Furthermore,
      the result also indicated that kansui stir-baked with vinegar protects LO2 cells
      from apoptosis by increasing the cell mitochondrial membrane potential
      (DeltaPsim), decreasing the release of cytochrome c and inhibiting the activities
      of caspase-9 and caspase-3 as evidenced by means of high content screening (HCS),
      ELISA and western blotting. These results suggested that the stir-baking vinegar
      could reduce the hepatotoxicity of kansui by effectively decreasing the contents
      of toxic terpenoids and inhibiting the intrinsic pathway of hepatocyte cell
      apoptosis. In conclusion, the study provided significant data for promoting safer
      and better clinical use of this herb. 

PMID- 24896264
TI  - A novel phage-library-selected peptide inhibits human TNF-alpha binding to its
      receptors.
AB  - We report the identification of a new human tumor necrosis factor-alpha (TNF
      alpha) specific peptide selected by competitive panning of a phage library.
      Competitive elution of phages was obtained using the monoclonal antibody
      adalimumab, which neutralizes pro-inflammatory processes caused by over
      production of TNF-alpha in vivo, and is used to treat severe symptoms of
      rheumatoid arthritis. The selected peptide was synthesized in monomeric and
      branched form and analyzed for binding to TNF-alpha and competition with
      adalimumab and TNF-alpha receptors. Results of competition with TNF-alpha
      receptors in surface plasmon resonance and melanoma cells expressing both TNF
      receptors make the peptide a candidate compound for the development of a novel
      anti-TNF-alpha drug. 

PMID- 24896265
TI  - Synthesis of caffeic acid amides bearing 2,3,4,5-tetra
      hydrobenzo[b][1,4]dioxocine moieties and their biological evaluation as antitumor
      agents.
AB  - A series of caffeic acid amides D1-D17 bearing 2,3,4,5-tetrahydrobenzo
      [b][1,4]dioxocine units has been synthesized and their biological activities
      evaluated for potential antiproliferative and EGFR inhibitory activity. Of all
      the compounds studied, compound D9 showed the most potent inhibitory activity
      (IC50=0.79 MUM for HepG2 and IC50=0.36 MUM for EGFR). The structures of compounds
      were confirmed by 1H-NMR, ESI-MS and elemental analysis. Among all, the structure
      of compound D9 ((E)-N-(4-ethoxyphenyl)-3-(2,3,4,5-tetrahydrobenzo[b][1,4]dioxocin
      8-yl)acrylamide) was also determined by single-crystal X-ray diffraction
      analysis. Compound D9 was found to be a potential antitumor agent according to
      biological activity, molecular docking, apoptosis assay and inhibition of HepG2.

PMID- 24896267
TI  - The annual training periodization of 8 world champions in orienteering.
AB  - One year of training data from 8 elite orienteers were divided into a transition
      phase (TP), general preparatory phase (GPP), specific preparatory phase (SPP),
      and competition phase (CP). Average weekly training volume and frequency, hours
      at different intensities (zones 1-3), cross-training, running, orienteering,
      interval training, continuous training, and competition were calculated. Training
      volume was higher in GPP than TP, SPP, and CP (14.9 vs 9.7, 11.5, and 10.6 h/wk,
      P < .05). Training frequency was higher in GPP than TP (10 vs 7.5 sessions/wk, P
      < .05). Zone 1 training was higher in GPP than TP, SPP, and CP (11.3 vs 7.1, 8.3,
      and 7.7 h/wk, P < .05). Zone 3 training was higher in SPP and CP than in TP and
      GPP (0.9 and 1.1 vs 1.6 and 1.5 h/ wk, P < .05). Cross-training was higher in GPP
      than SPP and CP (4.3 vs 0.8 h/wk, P < .05). Interval training was higher in GPP
      than TP, SPP, and CP (0.7 vs 0.3 h/wk, P < .05). High-intensity continuous
      training was higher in GPP than CP (0.9 vs 0.4 h/ wk, P < .05), while competition
      was higher in SPP and CP than in TP and GPP (1.3 and 1.5 vs 0.6 and 0.3 h/wk, P <
      .01). In conclusion, these champion endurance athletes achieved a progressive
      reduction in total training volume from GPP to CP via a shortening of each
      individual session while the number of training sessions remained unchanged. This
      decrease in training volume was primarily due to a reduction in the number of
      hours of low-intensity, non-sport-specific cross-training. 

PMID- 24896266
TI  - Treatment for stable coronary artery disease: a network meta-analysis of cost
      effectiveness studies.
AB  - INTRODUCTION AND OBJECTIVES: Numerous studies have assessed cost-effectiveness of
      different treatment modalities for stable angina. Direct comparisons, however,
      are uncommon. We therefore set out to compare the efficacy and mean cost per
      patient after 1 and 3 years of follow-up, of the following treatments as assessed
      in randomized controlled trials (RCT): medical therapy (MT), percutaneous
      coronary intervention (PCI) without stent (PTCA), with bare-metal stent (BMS),
      with drug-eluting stent (DES), and elective coronary artery bypass graft (CABG).
      METHODS: RCT comparing at least two of the five treatments and reporting clinical
      and cost data were identified by a systematic search. Clinical end-points were
      mortality and myocardial infarction (MI). The costs described in the different
      trials were standardized and expressed in US $ 2008, based on purchasing power
      parity. A network meta-analysis was used to compare costs. RESULTS: Fifteen RCT
      were selected. Mortality and MI rates were similar in the five treatment groups
      both for 1-year and 3-year follow-up. Weighted cost per patient however differed
      markedly for the five treatment modalities, at both one year and three years
      (P<0.0001). MT was the least expensive treatment modality: US $3069 and 13 864
      after one and three years of follow-up, while CABG was the most costly: US $27
      003 and 28 670 after one and three years. PCI, whether with plain balloon, BMS or
      DES came in between, but was closer to the costs of CABG. CONCLUSIONS:
      Appreciable savings in health expenditures can be achieved by using MT in the
      management of patients with stable angina.

PMID- 24896268
TI  - The NFL-TBS.40-63 anti-glioblastoma peptide disrupts microtubule and
      mitochondrial networks in the T98G glioma cell line.
AB  - Despite aggressive therapies, including combinations of surgery, radiotherapy and
      chemotherapy, glioblastoma remains a highly aggressive brain cancer with the
      worst prognosis of any central nervous system disease. We have previously
      identified a neurofilament-derived cell-penetrating peptide, NFL-TBS.40-63, that
      specifically enters by endocytosis in glioblastoma cells, where it induces
      microtubule destruction and inhibits cell proliferation. Here, we explore the
      impact of NFL-TBS.40-63 peptide on the mitochondrial network and its functions by
      using global cell respiration, quantitative PCR analysis of the main actors
      directing mitochondrial biogenesis, western blot analysis of the oxidative
      phosphorylation (OXPHOS) subunits and confocal microscopy. We show that the
      internalized peptide disturbs mitochondrial and microtubule networks, interferes
      with mitochondrial dynamics and induces a rapid depletion of global cell
      respiration. This effect may be related to reduced expression of the NRF-1
      transcription factor and of specific miRNAs, which may impact mitochondrial
      biogenesis, in regard to default mitochondrial mobility. 

PMID- 24896270
TI  - Associated factors to self-rated health among hypertensive and/or diabetic
      elderly: results from Bambui project.
AB  - OBJECTIVE: This study investigated the associated factors with negative self
      rated health among hypertensive and/or diabetic elderly. METHODS: All the
      participants of Bambui Project elderly cohort who suffered from hypertension
      and/or diabetes and who answered the questionnaire without the help of a close
      informant were selected for this (n = 942). Covariates encompassed
      sociodemographic characteristics, social support, health behaviors, health status
      and use of health services. RESULTS: Negative self-rated health showed positively
      associated with dissatisfaction with social relations (PR = 1.98, 95%CI 1.42 -
      2.76), attendance at religious services less than once a month (PR = 1.96, 95%CI
      1.44 - 2.68; be smokers (PR = 1.64, 95%CI 1.24 - 2.17), presence of arthritis (PR
      = 1.35, 95%CI 1.07 - 1.71), depressive symptoms (PR = 1.81, 95%CI 1.37 - 2.39)
      and insomnia (PR = 1.37, 95%CI 1.06 - 1.78), having consulted the doctor two or
      more times in the last twelve months (PR = 2.18; 95%CI 1.14 - 4.19 and PR = 3.96;
      95%CI 2.10 - 7.48, respectively for "2 - 3" and "4+" visits), and have
      hypertension and diabetes (compared to the isolated presence of hypertension)
      CONCLUSIONS: Our results confirmed the multidimensional nature of self-rated
      health and were consistent with that observed in other national and international
      studies.

PMID- 24896269
TI  - Aspiration-based partner switching boosts cooperation in social dilemmas.
AB  - Most previous studies concerning linking dynamics often assumed that links
      pairing individuals should be identified and treated differently during topology
      adjusting procedure, in order to promote cooperation. A common assumption was
      that cooperators were expected to avoid being exploited by quickly breaking up
      relationships with defectors. Then the so-called prosocial links linking two
      cooperators (abbreviated as CC links hereafter) would be much favored by
      evolution, whereby cooperation was promoted. However, we suggest that this is not
      always necessary. Here, we developed a minimal model in which an aspiration-based
      partner switching mechanism was embedded to regulate the evolution of cooperation
      in social dilemmas. Individuals adjusted social ties in a self-questioning manner
      in line with the learning theory. Less game information was involved during
      dynamic linking and all links were tackled anonymously irrespective of their
      types (i.e., CD links, DD links, or CC links). The main results indicate that
      cooperation flourishes for a broad range of parameters. The denser the underlying
      network, the more difficult the evolution of cooperation. More importantly,
      moderate aspirations do much better in promoting the evolution of altruistic
      behavior and for most cases there exists the optimal aspiration level that most
      benefits cooperation. Too strong or too weak selection intensity turns out to be
      pretty conducive to the evolution of cooperation in such a dynamical system. 

PMID- 24896271
TI  - Risk and protective factors for non communicable diseases in the Belo Horizonte
      population: Vigitel 2008.
AB  - INTRODUCTION: The Non Communicable Diseases (NCD) are the main causes of death
      in, having known, avoidable the Risk Factor (RF) and susceptible to intervention.
      OBJECTIVE: Identify the prevalence of RF and protection for NCD in the Belo
      Horizonte, 2008. METHODOLOGY: Data were analyzed from Vigitel, in Belo Horizonte,
      2008. They are presented to the frequencies of RF according to gender, schooling,
      and calculated the p-value and the PR. RESULTS: Men showed more frequencie in the
      following RF: higher consumption of meat and milk with fats, soft drinks, abusive
      consumption of alcohol, drive after drinking, ex-smokers. Men presented in
      relation to protective factors statistically significant differences in
      consumption of beans and leisure-time physical activity. Women had the highest
      frequencies in the consumption of fruits and vegetables, protection against
      ultraviolet radiation, self-assessment of health as poor, and declared more
      morbidities such as: arterial hypertension, dyslipidemia, asthma and
      osteoporosis. Adults with low levels of education compared with high education
      (reference) presented the following PR: smoke PR 2.09 (95%CI 1.43 - 3.05);
      consumption of 20 cigarettes and more PR 2.54 (95%CI 1.19 - 5.43); overweight PR
      1.27 (95%CI 1.02 - 1.56); obesity PR 1.6 (95%CI 1.04 - 2.47); consumption of soft
      drinks PR 2,07 (95%CI 1.51 - 2.83); consumption of fruit and vegetable intake PR
      0.53 (95%CI 0.40 - 0.72); consumption of beans PR 1.15 (95%CI 1.05 - 1.27); watch
      TV PR 1.33 (95%CI 1.00 - 1.77); driving after alcohol consumption PR 0.14 (95%CI
      0.04 - 0.53); hypertension PR 1.75 (95%CI 1.37 - 2.24); diabetes PR 2.24 (95%CI
      1.23 - 4.09). CONCLUSION: The telephone surveys are an important method to
      monitor the distribution of risk and protective factors in the population and to
      permit to orient health promotion programs and prevention.

PMID- 24896272
TI  - Breast cancer mortality among patients attending a cancer hospital, Vitoria, ES.
AB  - This study aimed to investigate the association between mortality of breast
      cancer women and the social-demographic and clinical characteristics. During the
      mortality study of 1,086 women diagnosed with breast cancer and treated from 2000
      to 2005 at a cancer hospital in the city of Vitoria, Espirito Santo, medical
      records and tumor registration cards were controlled. The Mortality Information
      System and the Reclink program were used to identify 280 deaths. Patients were
      classified under death and non-death, and variables percentages were calculated.
      For variables that showed statistical significance, considering the level of
      0.10, the crude and adjusted odds ratio (OR) were calculated by logistic
      regression model. There was a correlation between mortality and the following
      variables: women coming from the Unified Health System (p = 0.014; OR = 2.38),
      negative c-erb B-2 tumor marker (p = 0.027; OR = 2.03), advanced (III and IV)
      staging (p = 0.001; OR = 6.89 and OR = 17.13, respectively), presence of
      metastasis (p = 0.001; OR = 18.23) and recurrence (p = 0.010; OR = 3.53).
      Mortality associated with staging underlines the necessity of warning the
      population about the benefits of early diagnosis of the disease of cancer. 

PMID- 24896273
TI  - Epidemiological profile of tuberculosis in the city of Belo Horizonte (MG), from
      2002 to 2008.
AB  - OBJECTIVE: To assess the epidemiological profile of tuberculosis in Belo
      Horizonte, Minas Gerais State, from 2002 to 2008. METHODS: For descriptive
      epidemiological study, the data were obtained from the municipal National Health
      Surveillance System, after obtaining approval from the Research Ethics Committee
      at the City Health Department. Incidence coefficient, average rates and
      stratified data analysis with significance level of p <= 0.05 were calculated.
      RESULTS: About 7.590 new tuberculosis cases were reported between 2002 and 2008.
      There was a slight reduction in the number of cases throughout the historical
      trend, with an average annual incidence rate of 46/100,000 inhabitants. The study
      also showed a male gender ratio of 1.84:1, a higher incidence coefficient in the
      age group between 40 and 59 years old (73/100,000) and a higher incidence of
      tuberculosis among people who only had primary education level. Pulmonary
      tuberculosis was the most prevalent form in every year of the study (p < 0,001).
      Among the cases reported with associated diseases, alcoholism was registered in
      47.9% and AIDS in 34.5%. Between 2002 and 2008, there was an increasing trend of
      cases treated under Directly Observed Treatment, accounting for 29.5% in total.
      Cure percentage rate was below the expected result (67.3%) and non-adherence to
      treatment showed a high total percentage (17.9%). CONCLUSION: The results
      indicated that tuberculosis control actions need to be intensified with
      investments on professional training, systemic audits of the information system,
      improved integration between AIDS/tuberculosis programs and raising awareness of
      the disease with the goal of mobilizing the society.

PMID- 24896274
TI  - Spatial distribution of dengue disease in municipality of Mossoro, Rio Grande do
      Norte, using the Geographic Information System.
AB  - The dengue viral infection is one of the most relevant vector-borne diseases in
      the world. The disease can manifest in a variety of forms, from asymptomatic to a
      condition of dengue hemorrhagic fever (DHF). The last reported cases in Brazil
      correspond to 80% of the cases reported in the Americas, which emphasizes the
      magnitude of the problem. This study was conducted using Geographic Information
      System (GIS) techniques, in order to evaluate the spatial distribution of the
      disease in the urban area of Mossoro, Rio Grande do Norte. In the period between
      2001 and 2007, 867 new cases were listed. About 85.7% of the addresses were
      georeferenced, with a larger number of cases, 14.8%, in the neighborhoods of
      Santo Antonio and Santa Delmira (north region), and 11.7% in the neighborhoods of
      Conjunto Vingt-Rosado and Alto de Sao Manoel (east region). There were 18
      confirmed cases of dengue hemorrhagic fever associated with regions with the
      highest incidence of classic cases of the disease. The use of Geographic
      Information System (GIS) proved a great benefit for better visualization of the
      endemic, especially in elucidating the actual distribution of dengue cases in the
      county and providing an effective tool for planning the monitoring of the disease
      at a local level. 

PMID- 24896275
TI  - Realities of leprosy control: updating scenarios.
AB  - In the light of successive therapeutical difficulties for leprosy control, the
      application of drug therapy combination over the last decades has brought about
      an expectation of cure for leprosy patients and also for the elimination of this
      illness as a Public Health problem. However, there has been a progressive
      reduction in the prevalence of leprosy, but without any apparent impact on
      transmission, which has led to recognized need for solid assessment of respective
      epidemiological evidence as grounds for interventions to solve the problem. In
      this regard, here we present a retroanalytical qualitative and quantitative
      study, combined with a prospective diachronic approach, based on the association
      of documental review techniques and analysis of content, involving the following
      phases in succession: assembly of an operational scheme, execution of search
      strategy, application of criteria, selection of studies, data extraction and
      processing, implementation of analysis plan and preparation of final text. The
      appropriate execution of the procedures, as applied, allows us to obtain and
      discuss the identification of three main scenarios: the elimination of the
      illness as a public health problem (Neglected Illness); therapeutic aspects
      (Resistance; Relapse; Non-Adherence; Persistence) and complexity (complications
      and physical incapacities). The conclusions that have been reached
      indicate,mainly, that the reality of leprosy control with the use of combination
      drug therapy, still needs to be handled with care, even more so as this is just a
      fragment of the set of people once under medical attention, which also correspond
      to a parcel of the set of people affected by the ailment. 

PMID- 24896276
TI  - Weight and height of people living with HIV/AIDS attended by the Brazilian
      National Health System.
AB  - The nutritional status of people living with HIV/AIDS (PLWHA) is related to
      morbidity and mortality and its monitoring is important in the maintenance of the
      health status. This is a cross-sectional study carried out in Brazilian National
      Health System in the Municipality of Sao Paulo. It describes anthropometrical
      characteristics: weight and height; indices of weight for height (W/H), height
      for age (H/A), body mass index for age (BMI/A) and Z score for height and weight.
      The study includes 772 participants from all ages: children, adolescents, adults
      and elderly. The graphical analysis shows that in under-5s and in the 5 to 19
      years old group, the W/H, the H/A and the BMI/A curves are similar to the
      reference population with an exception in the H/A for 5 to 19 years old group
      which is left-shifted (mean Z = -0.66). In the case of adults, graphics for the
      study population show median weight apparently lower than in the reference
      population for most age groups in the case of men, and when age is greater in
      women. The proportion of people over 20 years old with AIDS on anti-retroviral
      therapy is lower when coinfection is present (p < 0.001). The findings of the
      study showed that, for children and adolescents with HIV/AIDS, the average weight
      and height are lower than the values for non infected population. For adults and
      elderly, the weight average is lower than the reference population with a
      worsening among coinfected patients. This underscores the need to direct more
      effort in nutritional actions thus helping enhance the health status of this
      group. 

PMID- 24896277
TI  - Injuries caused by venomous animals and folk medicine in farmers from Cuite,
      State of Paraiba, Northeast of Brazil.
AB  - Injuries caused by venomous animals reported by the agricultural workers from the
      municipality of Cuite, Curimatau region of Paraiba State, Northeast of Brazil,
      and the practices of folk medicine which they use to treat these cases were
      studied in this work from June to August 2010. The farmers studied aged from 11
      to 90 years. The number of people who reported cases of injury by these animals
      in their families was high (89.3%). Scorpions, wasps, bees and snakes were the
      most cited and the extremities of the body (hands, feet, legs and head) were the
      most affected. The practice of folk medicine to treat these injuries includes
      various procedures ranging from ritualistic treatments, use of animals or parts
      of them, and some herbal preparations. The folk treatment was reported as
      effective by most of the workers injured (63.9%). Body parts of dead snakes are
      used in various zootherapic treatments. In the imaginary of the agricultural
      workers the venomous animals are considered hazardous (48.7%) or disgusting
      (11.3%), and several parts of such animals as the rattle, bee sting or snake
      leather are used as amulet. Several legends have also been reported about snakes,
      scorpions and bees. The need for educational activities that aim to clarify these
      workers about the dangers of such practices is urgent. 

PMID- 24896278
TI  - Prevalence of anxiety in patients admitted to a university hospital in southern
      Brazil and associated factors.
AB  - OBJECTIVE: To identify the prevalence of anxiety in adults hospitalized in the
      clinical ward of a university hospital and to analyze the possible associated
      factors. METHOD: A cross-sectional study was performed in a university hospital.
      All interviewees answered a specific questionnaire and the Hospital Anxiety and
      Depression Scale. A Poisson regression was used to calculate prevalence ratios
      with 95% confidence intervals. RESULTS: 282 patients were enrolled. The
      prevalence of anxiety was 33.7% (95%CI 28.2 - 39.3). Characteristics associated
      with the outcome were female gender (RP 2.44), age >= 60 years (PR 0.65),
      consultation in primary health care (PR 2.37), estimated time of contact between
      patient and student > 30 min (RP 1.36), high blood pressure (PR 1.57), diabetes
      mellitus (PR 1.43), and obesity (RP 1.43). CONCLUSION: This study found
      prevalence of high anxiety. It may be associated with certain characteristics of
      the patients (gender, age, chronic diseases); the medical appointment in primary
      care and time (estimated by the patient) that the student remained with this
      patient. The need for a focused approach to mental health care within the
      hospital has been discussed for a long time. The particularity of this study
      refers to the environment of a university hospital and to what extent the
      environment and the patient's relationship with the student are associated with
      higher prevalence of anxiety.

PMID- 24896279
TI  - Mortality by suicide: a focus on municipalities with a high proportion of self
      reported indigenous people in the state of Amazonas, Brazil.
AB  - OBJECTIVE: To analyze mortality rates and to describe the demographic and
      epidemiological characteristics of suicides recorded in the state of Amazonas.
      METHODS: A descriptive and retrospective study has been carried out with emphasis
      on municipalities, which have shown, simultaneously, a high mortality rates and a
      high proportion of self-reported indigenous population, based on 2005 - 2009 data
      as provided by the Informatics Department of the Unified National Health System.
      RESULTS: Among the general population of the state of Amazonas, the mortality
      rate, by suicide, of 4.2/100.000 inhabitants has been reported, similar to that
      of Manaus (4.6/100.000 inhabitants). In contrast, at Tabatinga (25.2/100.000
      inhabitants), at Sao Gabriel da Cachoeira (27.6/100.000 inhabitants) and at Santa
      Isabel do Rio Negro (36.4/100.000 inhabitants), municipalities, where the
      proportion of self-reported indigenous population is high, besides the taxes
      being notably higher, it was observed that most of the suicides has occurred
      among men; among young men aged between 15 - 24 years; at home; by hanging;
      during "weekend" and among the indigenous population. DISCUSSION: Our findings
      have unveiled that suicide comes forth as a serious public health issue in some
      municipalities in the state of Amazonas, further indicating that the event occurs
      within very specific contexts, and that the dimension and the magnitude of the
      problem can be even more serious among populations or in territories exclusively
      inhabited by indigenous people.

PMID- 24896280
TI  - Conformity of pre-gestational weight measurement and agreement of anthropometric
      data reported by pregnant women and those recorded in prenatal cards, City of Rio
      de Janeiro, 2007-2008.
AB  - OBJECTIVE: To assess the conformity of the weight measurement process in the pre
      gestational care offered in the city of Rio de Janeiro by primary units and
      hospitals of the National Health System, as well as to verify the agreement
      between the anthropometric data reported by pregnant women and those recorded in
      prenatal cards. METHOD: A cross-sectional study was conducted in 2007 - 2008 with
      two cluster samples: one to obtain a sample of pregnant women to be interviewed
      and another one for the weight measurement procedures to be observed. The
      conformity of the weight measurement process was evaluated according to the
      Ministry of Health standards, and the agreement between the two sources of
      anthropometric data was evaluated using mean differences, Bland-Altman method,
      intraclass correlation coefficient (ICC) and weighted Kappa. RESULTS: Out of the
      twelve criteria for weight measurement evaluation (n = 159 observations), three
      weren't in conformity (< 50% of conformity), two of them only need to be assessed
      when the scale is mechanical. For the interviewed pregnant women (n = 2,148), who
      had the two sources of anthropometric data, there was a tendency of self-reported
      height overestimation and pre-gestational and current weight and Body Mass Index
      underestimation. Accordance between the two sources of anthropometric
      information, according to ICC and weighted Kappa, were high (> 0.80). CONCLUSION:
      Studies may use weight and height information reported by pregnant women, in the
      absence of prenatal cards records, when it is an important economy to their
      execution, although the improvement of these two sources of information by means
      of better anthropometric process is necessary.

PMID- 24896281
TI  - Social inequalities in neonatal mortality and living condition.
AB  - OBJECTIVE: To evaluate the association between the spatial distribution of
      neonatal mortality and living conditions, and to analyze trends in the social
      inequalities, related to this mortality, in Salvador, Bahia, Brazil, 2000 - 2006.
      METHODS: The city's Information Zones, the unit of analysis used in this study,
      were grouped into strata reflecting high, intermediate, low and very low living
      conditions, based on a living conditions index (LCI). Neonatal mortality rates
      were calculated for each stratum. Spearman's correlation, linear regression and
      relative risks were used in the data analysis. RESULTS: Neonatal mortality in
      Salvador was found to be associated with living conditions, with risks of 53, 56
      and 59% greater, respectively, in the intermediate, low and very low strata, when
      compared to the high living conditions stratum. Only the intermediate living
      conditions stratum shows a significant decline in neonatal mortality (beta = 
      0.93; p = 0.039). In the stratum of high living conditions, it was observed a
      stagnation of this mortality. CONCLUSIONS: Poorer living conditions were
      associated to higher risks of neonatal mortality. The slight decline in social
      inequalities, found in neonatal mortality, was due to a decline in the
      intermediate living conditions stratum. Although dependent on the access to
      quality healthcare services and life support technologies, a more consistent
      reduction in the neonatal mortality and its associated inequalities will only be
      achieved when broader-reaching public policies are implemented, improving the
      living conditions, and mainly focusing on priority groups.

PMID- 24896282
TI  - Social and environmental inequities in dental caries among indigenous population
      in Brazil: evidence from 2000 to 2007.
AB  - This ecological study investigated the association between social and
      environmental inequities and dental caries among indigenous people in Brazil.
      Dental caries data were gathered from articles identified from electronic
      databases for the period between 2000 and 2007. Independent variables were
      obtained from the census of Health Information System for Sanitation Indigenous
      Populations. Multiple linear regression analysis was conducted to test the
      association between social and environmental characteristics and dental caries
      (DMFT index) according to the age group. Results were analyzed for 48 indigenous
      peoples from 19 selected studies. The occurrence of dental caries in particular
      age groups was inversely associated with the location of villages outside the
      Amazon region (12, 15 - 19, and 20 - 34 years), availability of electricity (15 -
      19 and 20 - 34 years) and proportion of households covered with straw/thatch (20 
      34 years). The presence of schools was statistically associated with higher DMFT
      averages (15 - 19 and 20 - 34 years). It can be concluded that aspects of
      location and existing infrastructure in indigenous communities, which are linked
      to the availability of oral health services, are associated with the occurrence
      of dental caries in indigenous populations in Brazil. 

PMID- 24896283
TI  - Are recurrent denture-related sores associated with the risk of oral cancer? A
      case control study.
AB  - OBJECTIVES: This study aimed to assess the hypothesis that recurrent denture
      related sores association may be associated with the risk of oral cancer.
      METHODS: We conducted a hospital-based case-control study comprising 71 new cases
      of oral cancer in two hospitals in Sao Paulo, Brazil, and 240 controls without
      cancer, recruited from outpatient units of the same hospitals. All cases had
      histologically confirmed squamous cell carcinoma in anatomic sites of the mouth
      that may be specifically consi-dered at risk of sores by ill-fitting dentures.
      Denture-related sores were assessed by the self-report of recurrent oral sores
      due to the use of ill-fitting complete removable dental prosthesis. Associations
      were assessed by multivariate logistic regression conditioned on socio
      demographic and behavioral characteristics. RESULTS: The association between ill
      fitting dentures and oral cancer was statistically significant in the
      multivariate model: odds ratio 3.98; 95% confidence interval 1.06 - 14.96. The
      specific assessment of association between tumors in the lower jaw and sores by
      mandibular dentures confirmed this result: odds ratio 6.39; 95% confidence
      interval 1.49 - 29.52. CONCLUSION: The potential contribution of denture-related
      sores to oral carcinogenesis still fuels controversies. This study reinfor-ces
      the hypothesis that recurrent denture-related sores may be associated with the
      risk of oral cancer. Results reported here also suggest that an appropriate
      application and monitoring of dental prosthesis represent a non-negligible scope
      for cancer prevention.

PMID- 24896284
TI  - Diagnostic validity of self-reported oral health outcomes in population surveys:
      literature review.
AB  - Population-based health surveys are increasingly including self-reported oral
      health measures. However, their validity is frequently questioned. This study
      aimed to review the diagnostic validity of self-reported oral health measures -
      regarding periodontal conditions, number of remaining teeth and use and need of
      prostheses - and to present prototypes of oral health items to assess periodontal
      conditions. Papers published between 1991 and 2011 were identified through PubMed
      database. The sample profile, the sample size and the methods used in each study
      were analyzed, as well as the sensitivity, specificity, positive and negative
      predictive values of the oral health items. Periodontists were contacted, using a
      standardized text, sent by e-mail, which asked them to provide self-reported
      items regarding periodontal conditions. We reviewed 19 studies; 13 assessed
      periodontal conditions; five, the number of remaining teeth and four, the use and
      need of prosthesis - some studies evaluated two or more conditions
      simultaneously. Five of the eight periodontists suggested questions to assess
      periodontal conditions. The maximum and the minimum sensitivity values to assess
      periodontal conditions, number of remaining teeth and use and need of prosthesis
      were 100 and 2%; 91 and 21%; 100 and 100%; respectively; the maximum and the
      minimum specificity values were 100 and 18%; 97 and 96%; 93 and 93%;
      respectively. In conclusion, there are acceptable sensitivity and specificity
      values for number of remaining teeth and use and need of prosthesis only.
      Finally, we consider there is the need for further studies in the national
      context, in order to assess the impact of the questions about self-reported oral
      health conditions in epidemiological analyses. Therefore, it will be possible to
      empirically verify if self-reported questions can be used in such studies. 

PMID- 24896286
TI  - Prevalence of weight-loss strategies of young adults from the 1982 birth cohort
      in Pelotas, RS.
AB  - The objective of this article was to identify, among the members of the 1982
      birth cohort in Pelotas, those who were trying to lose weight at the age of 23,
      and which strategies they used. From 2004 to 2005, 4,297 individuals from the
      1982 cohort were interviewed. The effects of demographic, socioeconomic and
      behavioral factors on the prevalence of any strategy to lose weight in the past
      year were assessed in a cross-sectional analysis with the Poisson regression. Out
      of all the youngsters interviewed, 28.5% reported having used some strategy to
      lose weight. In the adjusted analysis, gender, schooling, family income, body
      mass index and smoking were associated with the use of some strategy. The
      strategy used by most of the young people was diet followed by physical activity.
      The results showed that appropriate preventive measures and body weight control
      are necessary, along with public policies aimed at encouraging healthy habits
      among young people, including physical and dietary education. 

PMID- 24896287
TI  - Quality of life, social position and occupational groups in Brazil: evidence from
      a population-based survey.
AB  - This study investigates whether occupation, variable that reflects social
      position, is associated with good quality of life among Brazilians. It is a cross
      sectional study based on data obtained from a population-based survey carried out
      in Brazil in 2008. The sample composed of 12,423 Brazilians, older than 20 years.
      Physical and mental quality of life were both measured by SF-36 and scores were
      grouped in "above the mean" and "below the mean" to set binary outcomes. Logistic
      regression analysis was carried out to verify the impact of occupational position
      on the chances of better physical and mental quality of life, controlling it by
      socio-demographic and health variables. Results showed that Brazilians included
      on the labour market have better chances of a good physical and mental quality of
      life, even if controlled by other variables. 

PMID- 24896285
TI  - Iron supplementation among pregnant women: results from a population-based survey
      study.
AB  - OBJECTIVES: To measure the prevalence and risk factors associated with iron
      supplementation among pregnant women in the municipality of Rio Grande, Southern
      Brazil. METHODS: All mothers living in this municipality who had children in 2007
      were surveyed for demographic, socioeconomic and health care received during
      pregnancy and childbirth. The statistical analysis consisted of Poisson
      regression with robust adjustment of variance, and the measure of effect was
      prevalence ratio (PR). RESULTS: Among the 2,557 mothers interviewed (99% of
      total), 59% were supplemented with iron during pregnancy period. After adjusting
      for various confounding factors, a higher PR to iron supplementation was observed
      among teenagers, women with black skin color, primigravidae, who had six or more
      antenatal visits, who performed prenatal care in public sector and received
      vitamin during pregnancy. CONCLUSION: There is a clear need to increase the iron
      supplementation coverage of all pregnant women, especially among those currently
      considered with low gestational risk.

PMID- 24896288
TI  - Trends of chronic health effects associated to pesticide use in fruit farming
      regions in the state of Ceara, Brazil.
AB  - The lower valley of Jaguaribe has registered, since the XXI century, the arrival
      of transnational and regional companies, which led to deep transformations in
      this region. The increased use of the pesticides is one of the most important
      ones, being able to cause alterations in human procreation and leading to
      congenital deformations, besides premature birth and low weight newborns. This
      article is an ecological study related to the period from 2000 to 2010 in the
      population of some cities in the state of Ceara, and it was divided in two parts:
      the first one, a draft of historical series of morbidity and mortality databases
      and trend verification performed by a simple linear regression; the second one
      comprehends the calculation of the ratio of rates between cities that are highly
      exposed to pestiides and the cities selected for comparison, with history of
      little use of these substances. There was statistically considerable growth
      tendency (p = 0.026) in the number of hospitalized people with neoplasms.
      Analyzing the ratios of the rates in these same indicators, it is observed that
      the rates of hospitalized people with neoplasms were 1.76 times higher in the
      studied cities than in control cities (p < 0.0010). With regard to to fetal
      deaths, a statistically considerable increase was observed (p < 0.05) as to the
      mortality rates in the studied cities. Results suggest there was higher morbidity
      and mortality caused by neoplasms in the cities with broader use of pesticides,
      which could be influenced by production, environmental and social transformations
      associated to the process of deterritorialization induced by the expansion of the
      agricultural modernization over the morbidity and mortality profile of the
      population of lower Jaguaribe. This process is a reflex of the production
      chemical-dependent model adopted by the agribusiness companies, expanding the
      vulnerability of the country side population. 

PMID- 24896289
TI  - Accidents at work and living conditions among solid waste segregators in the open
      dump of Distrito Federal.
AB  - The work of recycling solid waste segregators allows a precarious livelihood, but
      triggers a disease process that exacerbates their health and well-being. This
      study aimed to estimate the prevalence of occupational accidents at the open dump
      in the Federal District and its associated factors. Most segregators have had an
      accident at work (55.5%), perceived the danger of their working environment
      (95.0%) and claimed they did not receive personal protective equipment (51.7%).
      Among other findings, 55.8% ate foods found in the trash, 50.0% experienced food
      insecurity at home and 44.8% received Bolsa Familia. There was a statistically
      significant relationship between work accidents and perception of dangerous work
      environment, household food insecurity and the presence of fatigue, stress or
      sadness (p < 0.05). On the other hand, the fellowship between the segregators was
      associated with a lower prevalence of accidents (p < 0.006). Women are the
      majority of the segregators (56.5%) and reported more accidents than men (p <
      0.025). We conclude that the solid waste segregators constitute a vulnerable
      community, not only from the perspective of labor, but also from the social and
      environmental circumstances. To reverse this situation, effective implementation
      of the National Policy of Solid Wastes is imperative, in association with
      affirmative policies to grant economic emancipation for this population. 

PMID- 24896290
TI  - Evaluation of the level of knowledge and compliance with standart precautions and
      the safety standard (NR-32) amongst physicians from a public university hospital,
      Brazil.
AB  - Brazil is the first country in the world to have broad coverage standard (NR-32)
      focused on protecting health workers exposed to biological risks. This study
      evaluated the degree of knowledge of the NR-32 Standard and the level of
      knowledge and compliance with the standard precautions. A cross-sectional study
      was conducted with 208 randomly selected health professionals; 93 of them were
      residents and 115 were physicians at a Brazilian Clinical Hospital. To collect
      information, the participants were interviewed and/or they completed semi
      structured questionnaires divided into three domains: knowledge of the standard,
      knowledge of biosafety, and compliance with standard precautions. Cronbach's
      alpha was used to assess internal consistency of the scales of knowledge and
      compliance with values above +0.75 indicating excellent agreement. Multivariate
      linear regression was used to evaluate the predictors for compliance with NR-32,
      biosafety, and standard precautions. Mean knowledge of the NR-32 Standard was 2.2
      (+/- 2.02) points (minimum 0 and maximum 7 points). The minimum expected mean was
      5.25 points. The mean knowledge of biosafety was 12.31 (+/- 2.10) points (minimum
      4 and maximum 16 points). The minimum expected mean was 12.75 points. The mean
      compliance with standard precautions was 12.79 (+/- 2.6) points (minimum 6 and
      maximum 18 points). The minimum expected mean was 13.5 points. The individual
      means for using gloves, masks and goggles during procedures and for not recapping
      needles were 2.69, 2.27, 1.20 and 2.14, respectively. The factors associated with
      knowledge of the NR-32 were: greater knowledge amongst those who studied at a
      public university and who had knowledge of biosafety. The knowledge of the NR-32
      Standard was low, but there was a good level of knowledge of biosafety issues.
      The compliance with standard precautions was acceptable in general, but was low
      for some of the evaluated precautions.

PMID- 24896291
TI  - Large scale low cost fabrication of diameter controllable silicon nanowire
      arrays.
AB  - We report on a novel solution etching method to fabricate vertically aligned
      aperiodic silicon nanowire (SiNW) arrays. We begin with a simple dewetting
      process to fabricate a monolayer of well-spaced metal particles in situ on a
      silicon wafer. The particles function as a sacrificial template to pattern a
      Ti/Au catalyst film into a metal mesh and the size of particles directly
      determines the diameter of SiNW. A conventional metal-assisted chemical etching
      process is then carried out with the obtained metal mesh as a catalyst to realize
      a vertically aligned SiNW array at a large scale and low cost. 

PMID- 24896293
TI  - Unraveling patterns of site-to-site synonymous rates variation and associated
      gene properties of protein domains and families.
AB  - In protein-coding genes, synonymous mutations are often thought not to affect
      fitness and therefore are not subject to natural selection. Yet increasingly,
      cases of non-neutral evolution at certain synonymous sites were reported over the
      last decade. To evaluate the extent and the nature of site-specific selection on
      synonymous codons, we computed the site-to-site synonymous rate variation (SRV)
      and identified gene properties that make SRV more likely in a large database of
      protein-coding gene families and protein domains. To our knowledge, this is the
      first study that explores the determinants and patterns of the SRV in real data.
      We show that the SRV is widespread in the evolution of protein-coding sequences,
      putting in doubt the validity of the synonymous rate as a standard neutral proxy.
      While protein domains rarely undergo adaptive evolution, the SRV appears to play
      important role in optimizing the domain function at the level of DNA. In
      contrast, protein families are more likely to evolve by positive selection, but
      are less likely to exhibit SRV. Stronger SRV was detected in genes with stronger
      codon bias and tRNA reusage, those coding for proteins with larger number of
      interactions or forming larger number of structures, located in intracellular
      components and those involved in typically conserved complex processes and
      functions. Genes with extreme SRV show higher expression levels in nearly all
      tissues. This indicates that codon bias in a gene, which often correlates with
      gene expression, may often be a site-specific phenomenon regulating the speed of
      translation along the sequence, consistent with the co-translational folding
      hypothesis. Strikingly, genes with SRV were strongly overrepresented for
      metabolic pathways and those associated with several genetic diseases,
      particularly cancers and diabetes. 

PMID- 24896294
TI  - Erythritol, a non-nutritive sugar alcohol sweetener and the main component of
      truvia(r), is a palatable ingested insecticide.
AB  - Insecticides have a variety of commercial applications including urban pest
      control, agricultural use to increase crop yields, and prevention of
      proliferation of insect-borne diseases. Many pesticides in current use are
      synthetic molecules such as organochlorine and organophosphate compounds. Some
      synthetic insecticides suffer drawbacks including high production costs, concern
      over environmental sustainability, harmful effects on human health, targeting non
      intended insect species, and the evolution of resistance among insect
      populations. Thus, there is a large worldwide need and demand for environmentally
      safe and effective insecticides. Here we show that Erythritol, a non-nutritive
      sugar alcohol, was toxic to the fruit fly Drosophila melanogaster. Ingested
      erythritol decreased fruit fly longevity in a dose-dependent manner, and
      erythritol was ingested by flies that had free access to control (sucrose) foods
      in choice and CAFE studies. Erythritol was US FDA approved in 2001 and is used as
      a food additive in the United States. Our results demonstrate, for the first
      time, that erythritol may be used as a novel, environmentally sustainable and
      human safe approach for insect pest control. 

PMID- 24896296
TI  - Genetic association of objective sleep phenotypes with a functional polymorphism
      in the neuropeptide S receptor gene.
AB  - BACKGROUND: The neuropeptide S receptor (NPSR1) and its ligand neuropeptide S
      (NPS) have received increased attention in the last few years, as both establish
      a previously unknown system of neuromodulation. Animal research studies have
      suggested that NPS may be involved in arousal/wakefulness and may also have a
      crucial role in sleep regulation. The single nucleotide polymorphism (SNP)
      rs324981 in NPSR1 has begun to shed light on a function of the NPS-system in
      human sleep regulation. Due to an amino acid exchange, the T-allele leads to an
      increased sensitivity of the NPSR1. In the only genome-wide association study to
      date on circadian sleep parameters in humans, an association was found between
      rs324981 and regular bedtime. However, the sleep parameters in this study were
      only measured by self-rating. Therefore, our study aimed to replicate these
      findings using an objective measure of sleep. METHODS: The study included n = 393
      white subjects (62-79 years) who participated in an actigraphic assessment for
      determining sleep duration, rest duration, sleep onset, rest onset and sleep
      onset latency. Genotyping of the SNP rs324981 was performed using the TaqMan
      OpenArray System. RESULTS: The genotype at rs324981 was not significantly
      associated with rest onset (bedtime) or sleep onset (p = .146 and p = .199,
      respectively). However, the SNP showed a significant effect on sleep- and rest
      duration (p = .007 and p = .003, respectively). Subjects that were homozygous for
      the minor T-allele had a significantly decreased sleep- and rest duration
      compared to A-allele carriers. CONCLUSION: The results of this study indicate
      that the sleep pattern in humans is influenced by the NPS-system. However, the
      previously reported association between bedtime and rs324981 could not be
      confirmed. The current finding of decreased sleep duration in T/T allele carriers
      is in accordance with studies in rodents reporting similar results after NPS
      application.

PMID- 24896297
TI  - An insight into the cytotoxic activity of phytol at in vitro conditions.
AB  - The cytotoxicity of the diterpene alcohol, phytol, was evaluated by using the MTT
      assay in vitro against seven tumour cells and one normal cell of human origin.
      The compound tested induced concentration-dependent cytotoxic response in all
      cell lines, demonstrating to be most and least effective against the breast
      adenocarcinoma MCF-7 and the prostate adenocarcinoma PC-3 cells, respectively
      (IC50 8.79 +/- 0.41 MUM and 77.85 +/- 1.93 MUM). The IC50 values towards the
      other five tumours (HeLa, HT-29, A-549, Hs294T and MDA-MB-231) ranged from 15.51
      to 69.67 MUM. However, mild toxicity was detected against the foetal lung
      fibroblast MRC-5 cells at the concentrations used (IC50 124.84 +/- 1.59 MUM).
      According to the experimental data obtained, this cost-effective natural product
      widely present in the biosphere may inspire the development of new drug-like
      substances with improved cytotoxic activity on breast cancer. 

PMID- 24896298
TI  - Bartonella henselae endocarditis and glomerulonephritis with dominant C3
      deposition in a 21-year-old male with a Melody transcatheter pulmonary valve:
      case report and review of the literature.
AB  - We report a case of a 21-year-old young man with underlying congenital heart
      disease who developed Bartonella henselae endocarditis of the right ventricular
      outflow tract (RVOT) conduit of his Melody transcatheter (percutaneous) pulmonary
      valve (TPV), with an initial presentation of glomerulonephritis with a dominant
      C3 pattern, with renal failure and circulating cryoglobulins. There are few
      reports of a glomerulonephritis with a dominant C3 pattern presenting as a
      manifestation of B. henselae endocarditis. While most cases of B. henselae
      endocarditis affect the aortic valve, in this case the valve damage was to the
      RVOT of the Melody TPV, a percutaneous transcatheter valve delivery system that
      had previously replaced his pulmonary homograft, which had become dysfunctional
      as a result of prior Streptococcus viridans endocarditis. The pulmonary homograft
      had been in place since childhood as a result of a Ross procedure to repair his
      congenital aortic stenosis. The patient's renal failure significantly improved
      after surgical resection of the infected RVOT and institution of appropriate
      antibiotic therapy.

PMID- 24896299
TI  - Flavonoids and other constituents from Aletris spicata and their chemotaxonomic
      significance.
AB  - Eleven compounds, including four flavonoids [(2R,3R)-2,3-dihydro-3,5-dihydroxy
      7,4'-dimethoxyflavone (1), 5-hydroxy-7,8,4'-trimethoxy-flavone (2), amentoflavone
      (10) and apigenin (11)], two penylpropanoids [sinapaldehyde (3) and 3-methoxy-4
      hydroxy-cinnamic aldehyde (4)], three phenolic acids [4-hydroxyl-3,5-dimethoxy
      benzaldehyde (5), 4-hydroxyacetophen-one (6) and p-hydroxybenzaldehyde (7)], one
      furan derivative [5-hydroxymethyl furfural (8)] and one steroid saponin [beta
      sitosterol-3-O-beta-d-glucoside (9)], were isolated and identified from Aletris
      spicata. Among them, compounds 1-7, 9 and 10 were reported from the genus Aletris
      for the first time. Furthermore, seven of them (1-6, 10) were obtained from the
      family Liliaceae for the first time. Chemotaxonomy of the isolated compounds is
      discussed briefly.

PMID- 24896300
TI  - Iron-rich drinking water and ascorbic acid supplementation improved hemolytic
      anemia in experimental Wistar rats.
AB  - Anemia is a frequent problem in both the primary and secondary health care
      programs. In contrast, most areas of northeast India are vulnerable to iron
      toxicity. In the present study, we documented the effect of administration of
      iron rich water on hemolytic anemia in a Wistar rats' animal model. Hemolytic
      anemia was induced by phenyl hydrazine through intraperitoneal route and
      diagnosed by the lowering of blood hemoglobin. After inducing the hemolytic
      anemia, 24 Wistar rats (n = 6 in four groups) were randomly assigned to 1 mg/l, 5
      mg/l, and 10 mg/l ferric oxide iron along with 1 mg/ml ascorbic acid administered
      through drinking water; a control group was treated with iron-free water. The
      hematological and biochemical parameters, iron levels in liver, spleen, and
      kidney were estimated after 30 d of treatment. In the group treated with 5 mg/l
      iron and ascorbic acid, a significant increase of serum iron and ferritin, and a
      decrease of TIBC (total iron binding capacity) were observed without changes in
      other biochemical parameters and histopathological findings. However, in the
      group treated with 10 mg/l iron and ascorbic acid, hematological changes with
      significantly higher values for white blood cell count, serum glutamic phospho
      transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase,
      glucose, splenic, and liver iron content, indicate potential toxicity at this
      supplementation level. Data suggest that the optimum concentration of iron (5
      mg/l) and ascorbic acid solution may improve anemic conditions and may be
      therapeutically beneficial in the treatment of iron deficiency anemia without any
      negative impact, while 10 mg/l in drinking water seems to be the threshold for
      the initiation of toxicity.

PMID- 24896302
TI  - The Gretzky approach is good for business and research.

PMID- 24896301
TI  - Red yeast rice and coenzyme Q10 as safe alternatives to surmount atorvastatin
      induced myopathy in hyperlipidemic rats.
AB  - Statins are the first line treatment for the management of hyperlipidemia.
      However, the primary adverse effect limiting their use is myopathy. This study
      examines the efficacy and safety of red yeast rice (RYR), a source of natural
      statins, as compared with atorvastatin, which is the most widely used synthetic
      statin. Statin interference with the endogenous synthesis of coenzyme Q10 (CoQ10)
      prompted the hypothesis that its deficiency may be implicated in the pathogenesis
      of statin-associated myopathy. Hence, the effects of combination of CoQ10 with
      either statin have been evaluated. Rats were rendered hyperlipidemic through
      feeding them a high-fat diet for 90 days, during the last 30 days of the diet
      they were treated daily with either atorvastatin, RYR, CoQ10, or combined
      regimens. Lipid profile, liver function tests, and creatine kinase were monitored
      after 15 and 30 days of drug treatments. Heart contents of CoQ9 and CoQ10 were
      assessed and histopathological examination of the liver and aortic wall was
      performed. RYR and CoQ10 had the advantage over atorvastatin in that they lower
      cholesterol without elevating creatine kinase, a hallmark of myopathy. RYR
      maintained normal levels of heart ubiquinones, which are essential components for
      energy production in muscles. In conclusion, RYR and CoQ10 may offer alternatives
      to overcome atorvastatin-associated myopathy. 

PMID- 24896303
TI  - Response to letter regarding "The effect of intercalated degrees on student
      involvement in academic medicine".

PMID- 24896305
TI  - Design of the national health security preparedness index.
AB  - The importance of health security in the United States has been highlighted by
      recent emergencies such as the H1N1 influenza pandemic, Superstorm Sandy, and the
      Boston Marathon bombing. The nation's health security remains a high priority
      today, with federal, state, territorial, tribal, and local governments, as well
      as nongovernment organizations and the private sector, engaging in activities
      that prevent, protect, mitigate, respond to, and recover from health threats. The
      Association of State and Territorial Health Officials (ASTHO), through a
      cooperative agreement with the Centers for Disease Control and Prevention (CDC)
      Office of Public Health Preparedness and Response (OPHPR), led an effort to
      create an annual measure of health security preparedness at the national level.
      The collaborative released the National Health Security Preparedness Index
      (NHSPI(TM)) in December 2013 and provided composite results for the 50 states and
      for the nation as a whole. The Index results represent current levels of health
      security preparedness in a consistent format and provide actionable information
      to drive decision making for continuous improvement of the nation's health
      security. The overall 2013 National Index result was 7.2 on the reported base-10
      scale, with areas of greater strength in the domains of health surveillance,
      incident and information management, and countermeasure management. The strength
      of the Index relies on the interdependencies of the many elements in health
      security preparedness, making the sum greater than its parts. Moving forward,
      additional health security-related disciplines and measures will be included
      alongside continued validation efforts. 

PMID- 24896304
TI  - A comparison between residual renal function and peritoneal clearance for Na/H2O
      and urea removal in peritoneal dialysis patients.
AB  - BACKGROUND: To compare the Na/H2O and urea removal between residual renal
      function (RRF) and peritoneal clearance (PC) in peritoneal dialysis patients. Try
      to explore the difference between RRF and PC in prognosis of chronic kidney
      disease patients who need peritoneal dialysis (PD) treatment. METHODS: Weekly
      Na/H2O and urea removal by PC and RRF were investigated individually. Independent
      samples t-test was carried out to compare the efficiency of removal between RRF
      and PC treatment. Pearson correlated analysis was applied to reveal the
      relationship between Na/H2O and urea removal and Kt/V. RESULTS: Although a higher
      Na/H2O removal rate by RRF was showed in this investigation, the difference was
      not statistical significant compared to the one by PC. On the other hand, urea
      removal by RRF was obviously higher than PC. For every 0.1 Kt/V, Na/H2O removal
      by RRF was distinctly higher than PD. The Na and H2O removal of RRF were 147.88
      +/- 83.72 mmol and 46.54 +/- 39.11 mmol, respectively; and the ones of PD were
      11.40 +/- 6.08 mmol and 4.47 +/- 4.79 mmol. By using statistical assay, the
      correlations relevance between Na/H2O removal and Kt/V in RRF were showed
      stronger than in PC. However, the total removal of Na/H2O showed a poor
      correlation with Kt/V in both RRF and PC. CONCLUSIONS: The removal efficiency of
      RRF is much higher than PC. This study suggests that it is important to adjust
      dialysis program when RRF gets declined. Also the correlation between Na/H2O
      removal rate and Kt/V is an important monitoring factor for the patients who are
      receiving peritoneal dialysis.

PMID- 24896306
TI  - A public health emergency preparedness critical incident registry.
AB  - Health departments use after-action reports to collect data on their experience
      in responding to actual public health emergencies. To address deficiencies in the
      use of such reports revealed in the 2009 H1N1 influenza pandemic and to develop
      an effective approach to learning from actual public health emergencies, we
      sought to understand how the concept and operations of a "critical incident
      registry," commonly used in other industries, could be adapted for public health
      emergency preparedness. We conducted a workshop with public health researchers
      and practitioners, reviewed the literature on learning from rare events, and
      sought to identify the optimal characteristics of a critical incident registry
      (CIR) for public health emergency preparedness. Several key critical
      characteristics are needed for a CIR to be feasible and useful. A registry
      should: (1) include incidents in the response in which public health agencies
      played a substantial role, are "meaningful," test one or more emergency
      preparedness capabilities, and are sufficiently limited in scope to isolate
      specific response issues; (2) be supported by a framework and standard protocols
      for including reports based on rigorous analysis of individual incidents and
      methods for cross-case analysis; and (3) include explicit incentives for
      reporting, to overcome intrinsic disincentives. With proper incentives in place,
      a critical incident registry can be a useful tool for improving public health
      emergency preparedness. Standard protocols for reporting critical events and
      probing analysis are needed to enable identification of patterns of successes and
      failures. 

PMID- 24896307
TI  - Efficiency and effectiveness of using nonmedical staff during an urgent mass
      prophylaxis response.
AB  - Using a simulated anthrax scenario, the Philadelphia Department of Public Health
      tested the readiness of a nonmedical closed point-of-dispensing (POD) site to see
      how rapidly and accurately it could provide medication to its internal
      population. This closed POD had developed and exercised its mass prophylaxis plan
      in conjunction with the local health department twice before, and the department
      was interested in assessing the impact of having no onsite department
      involvement. Two sessions were conducted as part of the overall exercise. In
      session 1, agency staff ran POD operations with no department involvement. During
      session 2, department staff provided an hour-long training session and oversaw
      POD operations. Mean throughput and accuracy rates of the 2 sessions were then
      compared to a previous health department public POD exercise staffed by
      department personnel and medical volunteers. The closed POD would be able to
      process the entire internal population in an estimated mean time of 23.9 hours.
      The accuracy rates for dispensing the correct medication during session 1 was
      84.7% and 92.4% during session 2 (p=0.0012). Overall accuracy was significantly
      higher in a previous local health department public POD exercise (88.6% vs.
      96.9%, p < 0.0001), as was pediatric dosing accuracy (p < 0.0001). We concluded
      that nonmedical closed PODs are a valuable strategy during a public health
      emergency that requires large segments of a population to receive medication
      rapidly. They must be activated judiciously, however, as their use may increase
      adverse events and potentially result in discontinuation of antibiotic
      prophylaxis should people choose not to finish the course. Local health
      department training and oversight reduce errors but may not always be available. 

PMID- 24896308
TI  - Microfluidics-based single-cell functional proteomics for fundamental and applied
      biomedical applications.
AB  - We review an emerging microfluidics-based toolkit for single-cell functional
      proteomics. Functional proteins include, but are not limited to, the secreted
      signaling proteins that can reflect the biological behaviors of immune cells or
      the intracellular phosphoproteins associated with growth factor-stimulated
      signaling networks. Advantages of the microfluidics platforms are multiple.
      First, 20 or more functional proteins may be assayed simultaneously from
      statistical numbers of single cells. Second, cell behaviors (e.g., motility) may
      be correlated with protein assays. Third, extensions to quantized cell
      populations can permit measurements of cell-cell interactions. Fourth, rare cells
      can be functionally identified and then separated for further analysis or
      culturing. Finally, certain assay types can provide a conduit between biology and
      the physicochemical laws. We discuss the history and challenges of the field then
      review design concepts and uses of the microchip platforms that have been
      reported, with an eye toward biomedical applications. We then look to the future
      of the field. 

PMID- 24896309
TI  - Nucleic acid aptamers for living cell analysis.
AB  - Cells as the building blocks of life determine the basic functions and properties
      of a living organism. Understanding the structure and components of a cell aids
      in the elucidation of its biological functions. Moreover, knowledge of the
      similarities and differences between diseased and healthy cells is essential to
      understanding pathological mechanisms, identifying diagnostic markers, and
      designing therapeutic molecules. However, monitoring the structures and
      activities of a living cell remains a challenging task in bioanalytical and life
      science research. To meet the requirements of this task, aptamers, as "chemical
      antibodies," have become increasingly powerful tools for cellular analysis. This
      article reviews recent advances in the development of nucleic acid aptamers in
      the areas of cell membrane analysis, cell detection and isolation, real-time
      monitoring of cell secretion, and intracellular delivery and analysis with living
      cell models. Limitations of aptamers and possible solutions are also discussed. 

PMID- 24896310
TI  - Resistive-pulse analysis of nanoparticles.
AB  - The development of nanopore fabrication methods during the past decade has led to
      the resurgence of resistive-pulse analysis of nanoparticles. The newly developed
      resistive-pulse methods enable researchers to simultaneously study properties of
      a single nanoparticle and statistics of a large ensemble of nanoparticles. This
      review covers the basic theory and recent advances in applying resistive-pulse
      analysis and extends to more complex transport motion (e.g., stochastic thermal
      motion of a single nanoparticle) and unusual electrical responses (e.g.,
      resistive-pulse response sensitive to surface charge), followed by a brief
      summary of numerical simulations performed in this field. We emphasize the forces
      within a nanopore governing translocation of low-aspect-ratio, nondeformable
      particles but conclude by also considering soft materials such as liposomes and
      microgels. 

PMID- 24896312
TI  - Nano/micro and spectroscopic approaches to food pathogen detection.
AB  - Despite continuing research efforts, timely and simple pathogen detection with a
      high degree of sensitivity and specificity remains an elusive goal. Given the
      recent explosion of sensor technologies, significant strides have been made in
      addressing the various nuances of this important global challenge that affects
      not only the food industry but also human health. In this review, we provide a
      summary of the various ongoing efforts in pathogen detection and sample
      preparation in areas related to Fourier transform infrared and Raman
      spectroscopy, light scattering, phage display, micro/nanodevices, and
      nanoparticle biosensors. We also discuss the advantages and potential limitations
      of the detection methods and suggest next steps for further consideration. 

PMID- 24896313
TI  - Energetics-based methods for protein folding and stability measurements.
AB  - Over the past 15 years, a series of energetics-based techniques have been
      developed for the thermodynamic analysis of protein folding and stability. These
      techniques include Stability of Unpurified Proteins from Rates of amide H/D
      Exchange (SUPREX), pulse proteolysis, Stability of Proteins from Rates of
      Oxidation (SPROX), slow histidine H/D exchange, lysine amidination, and
      quantitative cysteine reactivity (QCR). The above techniques, which are the
      subject of this review, all utilize chemical or enzymatic modification reactions
      to probe the chemical denaturant- or temperature-induced equilibrium unfolding
      properties of proteins and protein-ligand complexes. They employ various mass
      spectrometry-, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE)-, and optical spectroscopy-based readouts that are particularly
      advantageous for high-throughput and in some cases multiplexed analyses. This has
      created the opportunity to use protein folding and stability measurements in new
      applications such as in high-throughput screening projects to identify novel
      protein ligands and in mode-of-action studies to identify protein targets of a
      particular ligand. 

PMID- 24896311
TI  - Mass spectrometric analysis of histone proteoforms.
AB  - Histones play important roles in chromatin, in the forms of various
      posttranslational modifications (PTMs) and sequence variants, which are called
      histone proteoforms. Investigating modifications and variants is an ongoing
      challenge. Previous methods are based on antibodies, and because they usually
      detect only one modification at a time, they are not suitable for studying the
      various combinations of modifications on histones. Fortunately, mass spectrometry
      (MS) has emerged as a high-throughput technology for histone analysis and does
      not require prior knowledge about any modifications. From the data generated by
      mass spectrometers, both identification and quantification of modifications, as
      well as variants, can be obtained easily. On the basis of this information, the
      functions of histones in various cellular contexts can be revealed. Therefore, MS
      continues to play an important role in the study of histone proteoforms. In this
      review, we discuss the analysis strategies of MS, their applications on histones,
      and some key remaining challenges. 

PMID- 24896315
TI  - The use of clinical practice guidelines in determining standard of care.

PMID- 24896314
TI  - Humans, rights, and twenty-first century technologies: the making of the
      universal declaration on bioethics and human rights.

PMID- 24896316
TI  - Hold the sugar: regulating the consumption of sugar-sweetened beverages.

PMID- 24896317
TI  - Deadly dimethylamylamine: "health" supplements are killing consumers while
      current regulations impede FDA action.

PMID- 24896319
TI  - Multivariate equivalence tests for use in pharmaceutical development.
AB  - Statistical equivalence analyses are well-established parts of many studies in
      the biomedical sciences. Also in pharmaceutical development and manufacturing
      equivalence testing methods are required in order to statistically establish
      similarities between machines, process components, or complete processes. This
      article presents a choice of multivariate equivalence testing procedures for
      normally distributed data as generalizations of existing univariate methods. In
      all derived methods, variability is interpreted as nuisance parameter. The use of
      the proposed methods in pharmaceutical development is demonstrated with a
      comparative analysis of dissolution profiles. 

PMID- 24896320
TI  - Applications of lentiviral vectors in molecular imaging.
AB  - Molecular imaging provides the ability of simultaneous visual and quantitative
      estimation of long term gene expression directly from living organisms. To reveal
      the kinetics of gene expression by imaging method, often sustained expression of
      the transgene is required. Lentiviral vectors have been extensively used over
      last fifteen years for delivery of a transgene in a wide variety of cell types.
      Lentiviral vectors have the well known advantages such as sustained transgene
      delivery through stable integration into the host genome, the capability of
      infecting non-dividing and dividing cells, broad tissue tropism, a reasonably
      large carrying capacity for delivering therapeutic and reporter gene
      combinations. Additionally, they do not express viral proteins during
      transduction, have a potentially safe integration site profile, and a relatively
      easy system for vector manipulation and infective viral particle production. As a
      result, lentiviral vector mediated therapeutic and imaging reporter gene delivery
      to various target organs holds promise for the future treatment. In this review,
      we have conducted a brief survey of important lentiviral vector developments in
      diverse biomedical fields including reproductive biology. 

PMID- 24896321
TI  - Omega-3 PUFAs induce apoptosis of gastric cancer cells via ADORA1.
AB  - Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), including docosahexaenoic
      acid (DHA) and eicosapentaenoic acid (EPA), have been suggested to have anti
      cancer effects by epidemiological and clinical studies. However, their underlying
      anti-cancer mechanisms are still unclear. In this study, we examined the
      influence of two Omega-3 PUFAs (DHA and EPA) on the proliferation and apoptosis
      of gastric cancer (GC) cells, and found that DHA and EPA reduced the viability of
      GC cells and induced apoptosis by activating caspase-3. Moreover, we screened the
      expression profile of apoptosis-related genes in GC cells upon the treatment of
      DHA and/or EPA, and discovered that ADORA1, one subtype of adenosine receptor
      functionally involved in cell death, was up-regulated in response to DHA and EPA.
      Importantly, when GC cells were treated with a selective ADORA1 antagonist,
      DPCPX, the DHA/EPA-induced apoptosis was substantially reduced. Taken together,
      our results suggest that the anti-cancer effect of Omega-3 PUFAs on gastric
      cancer is at least partly dependent on activating the ADORA1-mediated apoptosis
      pathway. 

PMID- 24896322
TI  - Antioxidant targeting by deferiprone in diseases related to oxidative damage.
AB  - The design of antioxidant pharmaceuticals is a major challenge for the treatment
      of many clinical conditions and in aging. Free radical damage (FRD) is primarily
      catalysed by iron catalytic centers. Most of the natural and synthetic
      antioxidants are ineffective in inhibiting FRD because of the achievement of low
      concentrations at the affected tissues. Despite that many chelators inhibit FRD
      in vitro and in vivo, only Deferiprone (L1) has been shown to be effective and
      safe in the reversal of oxidative stress related tissue damage in iron overload
      and other conditions such as cardiomyopathy, acute kidney disease, Friedreich
      ataxia etc. Deferiprone, other chelators and their combinations could be used as
      main, adjuvant and alternative therapies in untreated conditions eg forms of
      cancer, Alzheimer's and Parkinson's diseases. Therapeutic targeting in each case
      requires specific chelator selection based on structure/activity correlation and
      consideration of other parameters eg ADMET. The ability of L1 to reach
      extracellular and intracellular compartments of almost all tissues including the
      brain is a major advantage for further development and use in many clinical
      conditions. 

PMID- 24896323
TI  - The role of the ubiquitin-proteasome pathway in cancer development and treatment.
AB  - Ubiquitination is a post-translational modification that plays a role in several
      cellular processes including cell cycle progression, cell proliferation, DNA
      replication and apoptosis. Ubiquitin-mediated signaling is frequently altered in
      cancer cells. Several tumor suppressors and oncogenes interact with enzymes of
      the ubiquitin-proteasome pathway that function in ubiquitin conjugation and
      deconjugation. Increasing evidence indicates that the ubiquitin-proteasome system
      (UPS) plays an important role in cancer development. Several small molecule
      inhibitors of the UPS have been applied to the treatment of cancer. The current
      review focuses on the role of the UPS in cancer development and the development
      of UPS inhibitors for cancer treatment. 

PMID- 24896324
TI  - Methods for detection of circulating cells in non-small cell lung cancer.
AB  - Circulating tumor cells (CTCs) from peripheral blood have been detected in most
      epithelial malignancies. CTCs are very heterogeneous and can be captured via
      different technologies based on their physical and biological properties. The
      detection rates have varied depending on the technology used for enumeration.
      Detection, monitoring, and molecular analysis of CTCs provide a powerful and
      noninvasive approach for the detection of early disease, assessing prognosis and
      therapeutic response in cancer patients. Non-small cell lung cancer (NSCLC) is
      one of the most lethal malignancies in humans. Compared with other solid tumors,
      the number of CTCs in NSCLC is relatively low. Nevertheless, NSCLC is a
      particularly important disease for CTC evaluation for prognostic purposes because
      of the lack of a reliable protein-based tumor marker. Molecular analyses of CTCs
      have provided new insights into the biology of metastasis with important
      implications for the clinical management of cancer patients. We review current
      and emerging technologies for CTC detection, with a focus on enrichment and
      molecular analysis of CTCs, and their potential clinical applications in NSCLC. 

PMID- 24896325
TI  - Targeting myeloid differentiation 2 for treatment of sepsis.
AB  - Sepsis continues to be a leading cause of intensive care unit (ICU) death. Gram
      negative bacteria are among the most important pathogens of sepsis and their LPS
      content is regarded to be an important stimulator that elicits the systemic
      inflammatory reaction. MD-2 is a small secreted glycoprotein that can bind to
      both the hydrophobic portion of LPS and to the extracellular domain of TLR4. The
      interaction between MD-2 and LPS bridges the two TLR4 molecules and induces the
      dimerization of LPS-MD-2-TLR4, which forms the structural basis for biological
      functions of TLR4/MD-2 complex. Due to its essential role in mediating the
      interaction between LPS and TLR4, MD-2 has been extensively explored as a
      therapeutic target for treatment of inflammatory disorders such as sepsis.
      Eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and
      antagonizes LPS binding to the same site. Although eritoran showed positive
      results in phase I and phase II clinical trials of severe sepsis, a phase III
      clinical study for severe sepsis has failed. More effective therapeutic
      strategies are in need to treat this devastating clinical disorder. 

PMID- 24896326
TI  - Cross-talk between heme oxygenase and peroxisome proliferator-activated receptors
      in the regulation of physiological functions.
AB  - Peroxisome-proliferator-activated-receptors (PPARs) are transcription factors
      belonging to the superfamily of nuclear receptors. The isoforms of PPAR include
      PPAR alpha, PPAR gamma and PPAR delta (also known as PPAR beta). Generally, PPARs
      potentiate insulin sensitivity, improve glucose/lipid metabolism, suppress
      inflammation/oxidative stress, attenuate excessive immune responses, regulate
      cell-growth and differentiation. Interestingly, agonists of PPAR gamma and PPAR
      alpha have been shown to upregulate the heme-oxygenase (HO)-system. Conversely,
      the HO-system also enhances PPAR alpha, and potentiates the expression and
      activity of PPAR gamma. Moreover, the HO-system and related products including
      bilirubin, biliverdin, carbon monoxide and ferritin have been shown to increase
      insulin sensitivity, improve glucose/lipid metabolism, suppress
      inflammation/oxidative stress, abate immune response, and modulate cell
      growth/differentiation. Therefore, an intimate, reciprocal, stimulatory and
      synergistic relationship between PPAR-signaling and the HO-system can be
      envisaged in the regulation of physiological functions. Thus, both the HO-system
      and PPARs-signaling participate in fine-tuning similar physiological functions,
      so novel pharmacological agents capable of optimizing this interaction should be
      sought. The coordinated regulation of PPAR-signaling and the HO-system may
      constitute the basis for future drug design. 

PMID- 24896327
TI  - Amylin in vasodilation, energy expenditure and inflammation.
AB  - Metabolic syndrome significantly increases the incidence of atherosclerosis
      related diseases including coronary artery disease, stroke, and type 2 diabetes.
      Recent progress has demonstrated that amylin, or islet amyloid polypeptide, is
      circulating multifunctional hormone and neuropeptide, which is co-secreted with
      insulin into the bloodstream by pancreatic beta cells and plays a very important
      role in regulating feeding, energy homeostasis and inflammation. Recent FDA
      approval of amylin analog pramlintide as a new drug for treating type 1 and 2
      diabetes positions amylin in the spotlight. In this analytical review, I
      summarize the recent progress on amylin studies in the following sections: 1)
      introduction to the molecular features of amylin; 2) amylin's amyloidogenic and
      proinflammatory effects; 3) a satiety hormone and new drug in increasing energy
      expenditure; and 4) a vasodilator inducing hypotension and tachycardia; and 5) a
      neuropeptide in depolarizing cholinergic neurons via closure of potassium
      channels. Continued improvement of our understanding on this multifunctional
      hormone would lead to future development of pramlintide as novel therapies for
      other inflammatory, hematological, metabolic, neurological and vascular diseases.

PMID- 24896328
TI  - The transition from constraint to regulation at the origin of life.
AB  - The origin of living dynamics required a local evasion of thermodynamic
      degradation by maintaining critical dynamical and structural constraints.
      Scenarios for life's origin that fail to distinguish between constrained
      chemistry and regulated metabolism do not address the question of how living
      processes first emerge from simpler constraints on molecular interactions. We
      describe a molecular model system consisting of coupled reciprocal catalysis and
      self-assembly in which one of the catalytic bi-products tends to spontaneously
      self-assemble into a containing shell (analogous to a viral capsule). In this
      process, which we call autogenesis, self-repair/reconstitution and reproduction
      are made possible by the fact that each of these linked self-organizing processes
      generates boundary constraints that promote and limit the other, and because this
      synergy thereby becomes embodied as a persistent rate-independent substrate
      transferrable constraint on the synergy of its component constraint-generating
      processes. It is proposed that this higher-order formal constraint is necessary
      and sufficient to constitute regulation as opposed to mere physico-chemical
      constraint. Two minor elaborations of this model system demonstrate how
      cybernetic and template-based regulation could emerge from this basic process. 

PMID- 24896329
TI  - Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice.
AB  - This study investigated the role and mechanism of Hyperhomocysteinemia (HHcy) on
      vascular remodeling in mice. We assessed the effect of HHcy on vascular
      remodeling using a carotid arterial vein patch model in mice with the gene
      deletion of cystathionine-beta-synthase (Cbs). Vein grafts were harvested 4 weeks
      after surgery. Cross sections were analyzed using Verhoeff-van Gieson staining,
      Masson's Trichrome staining, and immunostaining for morphological analysis and
      protein level assessment. The effect of Hcy on collagen secretion was examined in
      cultured rat aortic smooth muscle cells (RASMC). We found that Cbs-/- mice with
      severe HHcy exhibited thicker neointima and a higher percentage of luminal
      narrowing in vein grafts. In addition, severe HHcy increased elastin and collagen
      deposition in the neointima. Further, severe HHcy increases CD45 positive cells
      and proliferative cells in vein grafts. Finally, Hcy increases collagen secretion
      in RASMC. These results demonstrate that HHcy increases neointima formation,
      elastin and collagen deposition following a carotid arterial vein patch. The
      capacity of Hcy to promote vascular fibrosis and inflammation may contribute to
      the development of vascular remodeling. 

PMID- 24896331
TI  - The ADP-ribosyl cyclases--the current evolutionary state of the ARCs.
AB  - The major ADP-ribosylating enzyme families are the focus of this special issue of
      Frontiers in Bioscience . However, there is room for another family of enzymes
      with the capacity to utilize nicotinamide adenine dinucleotide (NAD): the ADP
      ribosyl cyclases (ARCs). These unique enzymes catalyse the cyclization of NAD to
      cyclic ADP ribose (cADPR), a widely distributed second messenger. However, the
      ARCs are versatile enzymes that can manipulate NAD, NAD phosphate (NADP) and
      other substrates to generate various bioactive molecules including nicotinic acid
      adenine dinucleotide diphosphate (NAADP) and ADP ribose (ADPR). This review will
      focus on the group of well-characterized invertebrate and vertebrate ARCs whose
      common gene structure allows us to trace their origin to the ancestor of
      bilaterian animals. Behind a facade of gene and protein homology lies a family
      with a disparate functional repertoire dictated by the animal model and the
      physical trait under investigation. Here we present a phylogenetic view of the
      ARCs to better understand the evolution of function in this family. 

PMID- 24896332
TI  - Burn to cycle: energetics of cell-cycle control and stem cell maintenance.
AB  - Stem cells have the unique ability to both maintain the stem cell population via
      self-renewal and give rise to differentiated cells. The balance between these
      options is very delicate and important for the short- and long-term maintenance
      of tissue homeostasis in an organism. Pathways involved in integrating
      environmental cues and in directing energy metabolism play an important role in
      the fate decisions of stem cells. In this review, we give an overview of the
      effects of cellular and systemic metabolic states on stem-cell fate in both
      embryonic and in adult stem cell populations, with a particular emphasis on cell
      cycle regulation. We discuss the major pathways implicated in sensing energetic
      status and regulating metabolism, including: the mTOR pathway, Forkhead-box-O
      transcription factors (FoxOs), Sirtuins, reactive oxygen species (ROS), AMP
      activated kinase (AMPK) and LKB1, the mTOR pathway and hypoxia inducible factors
      (HIFs). Given the importance of a correct balance between self-renewal and
      differentiation, understanding the mechanisms that drive stem-cell fate in
      different metabolic conditions will provide more insight in stem cell biology in
      both health and disease. 

PMID- 24896333
TI  - Insights into the next generation of cancer stem cell research.
AB  - The understanding of how cancer stem cells (CSCs) or tumor-initiating cells
      (TICs) behave is important in understanding how tumors are initiated and how they
      recur following initial treatment. More specifically to understand how CSCs
      behave, the different signaling mechanisms orchestrating their growth, cell cycle
      dynamics, differentiation, trans-differentiation and survival following cytotoxic
      challenges need to be deciphered. Ultimately this will advance the ability to
      predict how these cells will behave in individual patients and under different
      therapeutic conditions. Second or next-generation sequencing (NGS) capabilities
      have provided researchers a window into the molecular and genetic clockwork of
      CSCs at an unprecedented resolution and depth, with throughput capabilities
      allowing sequencing of hundreds of samples in relatively short timeframes and at
      relatively modest costs More specifically NGS gives us the ability to accurately
      determine the genomic and transcriptomic nature of CSCs. These technologies and
      the publicly available cancer genome databases, together with the ever increasing
      computing power available to researchers locally or via cloud-based servers are
      changing the way biomedical cancer research is approached. 

PMID- 24896330
TI  - Analysis of energy expenditure in diet-induced obese rats.
AB  - Development of obesity in animals is affected by energy intake, dietary
      composition, and metabolism. Useful models for studying this metabolic problem
      are Sprague-Dawley rats fed low-fat (LF) or high-fat (HF) diets beginning at 28
      days of age. Through experimental design, their dietary intakes of energy,
      protein, vitamins, and minerals per kg body weight (BW) do not differ in order to
      eliminate confounding factors in data interpretation. The 24-h energy expenditure
      of rats is measured using indirect calorimetry. A regression model is constructed
      to accurately predict BW gain based on diet, initial BW gain, and the principal
      component scores of respiratory quotient and heat production. Time-course data on
      metabolism (including energy expenditure) are analyzed using a mixed effect model
      that fits both fixed and random effects. Cluster analysis is employed to classify
      rats as normal-weight or obese. HF-fed rats are heavier than LF-fed rats, but
      rates of their heat production per kg non-fat mass do not differ. We conclude
      that metabolic conversion of dietary lipids into body fat primarily contributes
      to obesity in HF-fed rats. 

PMID- 24896334
TI  - TNF/TNFR: drug target for autoimmune diseases and immune-mediated inflammatory
      diseases.
AB  - Tumor necrosis factor, a regulatory cytokine, is extremely important signaling
      protein in the immune system. Among TNF family, TNF-alpha, TNF-beta are most the
      significant family members. Receptor of TNF namely TNFR1 and TNFR2 stimulates two
      different signaling pathways. TNFR1 signaling induces apoptosis pathway.
      Conversely, TNFR2 signaling triggers cell survival pathways. In this paper, we
      discuss about the TNF family with special reference to TNF-alpha/TNF-beta,
      different hypothesis related to autoimmunity and role of TNF, structure of TNF
      alpha/TNF-beta, distribution and normal activity in human body of TNF, receptors
      and signaling pathway for drug targeting. Finally, we also discuss about the
      therapy for autoimmune diseases and immune-mediated inflammatory diseases (IMIDs)
      using small molecules or therapeutic proteins.

PMID- 24896335
TI  - Identification of ADP-ribosylated peptides and ADP-ribose acceptor sites.
AB  - ADP-ribosylation is a post-translational modification of proteins that comprises
      the transfer of the ADP-ribose moiety from NAD+ to specific amino acid residues
      on substrate proteins or to ADP-ribose itself. It is catalyzed by ADP
      ribosyltransferases, a family of currently 22 human proteins that all possess an
      ADP-ribosyltransferase catalytic domain. ADP-ribosylation is a reversible
      modification that can be hydrolyzed by ADP-ribosylhydrolases. In order to define
      the functional role of cellular ADP-ribosylation and the functional contribution
      of distinct ARTD family members, it is necessary to identify all ADP-ribosylated
      proteins, as well as their modified residues in the context of different cellular
      conditions and stresses. Here, we summarize the most recent progress in defining
      the cellular ADP-ribosylome and the efforts to detect ADP-ribose acceptor sites
      by enzymatic reactions and mass-spectrometry. 

PMID- 24896337
TI  - Molecular, histopathological, and genomic variants of glioblastoma.
AB  - Glioblastoma (GBM), the most common primary brain tumor, has a poor median
      prognosis despite modern surgical, chemotherapeutic, and radiation modalities,
      which have shown little clinical efficacy. Initially categorized by
      clinicopathological classification into de novo primary GBM and secondary GBM,
      which arises from lower-grade glioma, genomic studies have elucidated several
      distinct genotypes. In addition, distinct patterns of dysregulated epidermal
      growth factor receptor, platelet-derived growth factor receptor, p53, phosphatase
      and tensin homolog, cell cycle proteins, and isocitrate dehydrogenase 1, as well
      as loss of heterozygosity in multiple chromosomes complicate the GBM mutational
      landscape. Even with the many approaches in targeting these mutations, a long
      standing clinical cure remains limited because of the tremendous heterogeneity
      and challenges in developing targeted treatments. Furthermore, this cancer
      utilizes ingenious approaches to subvert targeted agents and pathological
      variants of GBM demonstrate distinct molecular signatures, which may impact
      prognosis. This review discusses the collective understanding of GBM
      heterogeneity, including molecular, histopathological, and genomic features; why
      treatments have failed in the past; and how future clinical trials and therapies
      can be devised. 

PMID- 24896336
TI  - Resveratrol in epilepsy: preventive or treatment opportunities?
AB  - Resveratrol has been extensively investigated and has been demonstrated to have
      antioxidant properties, cancer chemopreventive activity, and the capacity to
      modulate the hepatic synthesis of triglycerides and cholesterol, among others
      well established actions. A noteworthy feature of resveratrol is its ability to
      cross the blood-brain barrier and to exhibit neuroprotective actions, mainly by
      their capacity to regulate redox pathways as well as the Sirtuin (SIRT) system,
      which in turn modulates gene transcription, controlling inflammation and
      apoptosis in the brain. Lately, evidence is accumulating with respect to the
      synergic effect of resveratrol with antiepileptic drugs and also its
      antiepileptic activity in various models of seizures. We discuss here recent
      evidence that strongly suggests that resveratrol acts as an anticonvulsant agent
      and could be a very effective method for reducing damage in neural tissue and
      even for preventing seizure development in coadjuvant antiepileptic therapy.

PMID- 24896339
TI  - Carboxylation-dependent conformational changes of human osteocalcin.
AB  - Osteocalcin (OCN) is a small noncollagenous protein mainly produced by
      osteoblasts and is highly represented in bones of most vertebrates. Human OCN
      contains up to three gamma-carboxyglutamic acid (Gla-OCN) residues at positions
      17, 21 and 24 which are thought to increase calcium binding strength, improving
      mechanical properties of the bone matrix. Recent studies revealed that OCN exerts
      also important endocrine functions, affecting energy metabolism and male
      fertility. The latter effect seems to be mediated by the uncarboxylated form of
      OCN (Glu-OCN). We employed human and mouse OCN as models of fully carboxylated
      and uncarboxylated OCN forms to investigate, by the use of circular dichroism and
      molecular dynamics simulations, the respective conformational properties and Ca2+
      affinity. Ca2+ binding was found to trigger a similar conformational transition
      in both Glu-OCN and Gla-OCN, from a disordered structure to a more compact/stable
      form. Notably, gamma-carboxylation increases the affinity of OCN for Ca2+ by > 30
      fold suggesting that, in physiological conditions, Gla-OCN is essentially Ca2+
      bound, whereas Glu-OCN circulates mainly in the Ca2+-free form. 

PMID- 24896338
TI  - The role of molecular biology in the diagnosis of lymphoid neoplasms.
AB  - In recent years, DNA-arrays, gene expression profiling and next-generation
      sequencing have elucidated the high complexity of genomic alterations occurring
      in lymphoid malignancies. These studies have also contributed to the
      identification of new diagnostic and prognostic biomarkers, which may represent
      possible targets for new therapeutic approaches. Such recent advances have
      significantly expanded the application of molecular tests to routine diagnostic
      hematopathology. It is thus conceivable that next-generation assays will soon
      flank traditional clonality tests and chromosomal translocation assays in the
      diagnostic work-up of difficult cases. This review is focused on the application
      of molecular biology techniques in the study of lymphoid tumors. Both
      conventional and next-generation tests will be addressed, with particular
      attention to their application to clinical practice. 

PMID- 24896340
TI  - Emergence of life: from functional RNA selection to natural selection and beyond.
AB  - This study tracks the rise, evolution and post-evolution of the genetic
      information system through emergence of life. The major stages traversed include
      prebiotic synthesis, functional RNA selection by metabolite, RNA World,
      peptidated RNA world, co-evolution of genetic code and amino acid biosynthesis,
      last universal common ancestor, Darwinian evolution and synthetic life. 

PMID- 24896341
TI  - CREG1 promotes angiogenesis and neovascularization.
AB  - Angiogenesis has long been considered as an important strategy for ischemic
      injury. It has been reported that cellular repressor of E1A-stimulated genes
      (CREG1) promotes human umbilical vein endothelial cell (HUVEC) proliferation,
      migration, and protects endothelial cell (EC) from apoptosis. However, its
      potential effect on angiogenesis remains undefined. In the present study, we
      investigated the role and mechanisms of CREG1 in promoting angiogenesis. We found
      that adenovirus-transduced CREG1 expression in HUVECs increases EC tube formation
      in matrigel and promotes neovascularization in matrigel plugs grafted into wild
      type mice. In addition, adenoviral CREG1 expression enhances filopodia formation,
      which is accompanied by increased expression of integrin-linked kinase (ILK) and
      activation of its downstream effector Cdc42. Hindlimb perfusion was significantly
      reduced after femoral artery ligation in CREG1 heterozygous knockout mice.
      Finally, adenoviral CREG1 was injected intramuscularly in gastrochemius and
      partially restores ischemic hindlimb perfusion. Our results demonstrated that
      CREG1 increases EC filopodia formation and vascular assembly via ILK-Cdc42
      activation and promotes neovascularization, which might be a therapeutic target
      for ischemic injury. 

PMID- 24896342
TI  - Fracture healing: from basic science to role of nutrition.
AB  - Fracture healing is a complex event that involves the coordination of different
      processes: initial inflammatory response, soft and hard callus formation, initial
      bony union and bone remodeling. This well-orchestrated series of biological
      events follows a specific temporal and spatial sequence that can be affected by
      biological factors, such as age and bone quality. There is some evidence that
      increased age is a considerable factor in the inhibition of fracture repair in
      human subjects. During aging there is an accumulation of damage that depends on
      the activation of inflammation processes and on changes in the circulating levels
      of inflammatory cytokines. In addition to the physiological slow down in the
      repair process, other conditions such as multiple comorbidities leading to
      polymedication are a frequent occurrence in elderly patients and can have an
      influence on this process. A further factor that affects bone metabolism is
      nutrition: bone quality, fragility fractures risk and fracture healing process
      are all influenced by the nutritional status. This review provides a summary of
      the immunological aspects of physiological fracture healing and of those
      nutritional factors which might play an important role in this process. 

PMID- 24896344
TI  - Novel biomarker for prostate cancer diagnosis by MRS.
AB  - Magnetic resonance spectroscopy (MRS) is a prospective tool for characterization
      of the chemical composition of tissues. In vivo MRS can be used for metabolite
      profiling in the prostate tissue to discriminate non-invasively carcinomas and
      healthy prostate. In this article different prostate metabolites have been
      discussed and how to exploit the MRS technique for the estimation of metabolites
      in prostate tissue quantitatively is elucidated. Choline, citrate, creatine, myo
      inositol metabolites can be considered as biomarker for localization of
      malignancy in the prostate and their ratio can be used for the determination of
      cancer tissue in the prostate gland. 

PMID- 24896343
TI  - Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha
      binding and activity.
AB  - PGRN was previously reported to bind to TNF receptors (TNFR) and is therapeutic
      against inflammatory arthritis. Here we present further evidences demonstrating
      the PGRN inhibition of TNF-alpha binding and activity, and clarifying the
      distinct mechanisms underlying TNF-alpha inhibition between PGRN and classic TNF
      alpha-binding inhibitors. In addition, we present evidences indicating that three
      TNFR binding domains of PGRN act independently in binding to TNFR. Furthermore,
      changing the order of three TNFR-binding domains in Atsttrin, a PGRN-derived
      molecule composed of these TNFR-binding domains, does not affect its anti
      inflammatory and anti-TNF activities in both collagen-induced inflammatory
      arthritis and human TNF-alpha transgenic mouse model. Taken together, these
      findings provide the additional molecular basis underlying PGRN/TNFR interaction
      and PGRN-mediated anti-inflammatory activity in various inflammatory diseases and
      conditions. 

PMID- 24896345
TI  - Aberrant histone modification in endometriosis.
AB  - Accumulating evidence suggests that epigenetic aberrations play definite roles in
      the pathogenesis of endometriosis. These include aberrations in genomic DNA
      methylation, microRNA expression, and histone modification. The aberrant histone
      modification status and the aberrant expression of histone deacetylases, which
      regulate histone acetylation, in endometriosis are the focus of this review.
      Herein, we summarize the recent studies in the following areas: (i)
      hyperacetylation of histones located in the promoter lesions of G-protein-coupled
      estrogen receptor 1, steroidogenic factor-1, and hypoxia-inducible factor-1 alpha
      genes and (ii) hypoacetylation of histones located in the promoter lesions of
      estrogen receptor alpha, homeobox A10, CCAAT/enhancer-binding protein alpha,
      p16(INK4a), p21(Waf1/Cip1), p27(Kip1), checkpoint kinase 2, death receptor 6, and
      E-cadherin genes. Further research from the viewpoint of epigenetics may lead to
      the identification of the candidate molecules that are aberrantly expressed in
      endometriosis and may help elucidate the pathogenesis of this disease. In
      addition, epigenetic drugs (including histone deacetylase inhibitors) show
      promise for the treatment of endometriosis by amending the expression of these
      epigenetically dysregulated genes.

PMID- 24896346
TI  - CREG promotes vasculogenesis by activation of VEGF/PI3K/Akt pathway.
AB  - Knowledge about factors regulating vasculogenesis remains limited. The cellular
      repressor of E1A-stimulated gene (CREG) has been reported to be involved in
      maintaining cellular differentiation and endothelial homeostasis, thus we
      hypothesize that CREG may be a novel factor regulating vasculogenesis. By using
      mouse embryonic stem cells (ESC) derived embryoid body (EB) model, we confirmed
      expression of CREG was significantly up-regulated during EB differentiation.
      Overexpression of CREG in ESC led to accelerated cystic EB formation, increased
      endothelial differentiation and vasculogenesis, whereas knockdown of CREG
      produced opposite phenotypes. Moreover, we found expression of vascular
      endothelial growth factor (VEGF) was up-regulated and PI3K/Akt pathway was
      activated in CREG-overexpressing EB. Administration of VEGF neutralizing antibody
      or PI3K/Akt pharmacological inhibitor LY294002 blocked the vasculogenesis in CREG
      over-expressing EB, while supplement of VEGF rescued vasculogenesis deficiency in
      CREG knocked down EB. Further study by Western blot determined that PI3K/Akt was
      a downstream effector of VEGF. We identify CREG as a novel factor in regulating
      endothelial differentiation and vasculogenesis via VEGF/PI3K/Akt pathway. 

PMID- 24896347
TI  - Lung tissue engineering.
AB  - Lung tissue engineering is an emerging field focused on the development of lung
      replacement devices and tissue to treat patients with end stage lung disease.
      Microfluidic based lung assist devices have been developed that have
      biomimetically designed vascular networks that achieve physiologic blood flow.
      Gas exchange in these devices occurs across a thin respiratory membrane. Designed
      for intrathoracic implantation as a bridge to transplant or destination therapy,
      these lung assist devices will allow ambulation and hospital discharge for
      patients with end stage lung disease. Decellularized lungs subsequently
      recellularized with epithelial and endothelial cells have been implanted in small
      animal models with demonstration of initial gas exchange. Further development of
      these tissues and scaling to large animal models will validate this approach and
      may be an organ source for lung transplantation. Initial clinical success has
      been achieved with decellularized tracheal implants using autologous stem cells.
      Development of microfluidic lung models using similar architecture to the lung
      assist device technology allows study of lung biology and diseases with
      manipulation of lung cells and respiratory membrane strain. 

PMID- 24896348
TI  - The role of invariant NKT cells in organ-specific autoimmunity.
AB  - Invariant NKT cells (iNKT) represent a unique subset of innate lymphocytes that
      play a dual role and exert a pro-inflammatory function and also a tolerogenic
      function that is crucial to maintain T cell tolerance and prevent autoimmune
      diseases like Multiple Sclerosis, Type 1 Diabetes, Rheumatoid Arhritis and
      Systemic Lupus Erithematosus (SLE). Although a large body of evidence indicated
      that iNKT cells are instrumental to counter-regulate T cell-mediated autoimmune
      diseases, there is still some controversy on whether iNKT cells can actively
      induce immunosuppression and directly dampen T cell autoimmunity. Moreover, the
      recent discovery of a distinct iNKT cell subset, the iNKT17 cells, with strong
      adjuvant and pro-inflammatory function raised the question on what is the role of
      NKT17 cells in the pathogenesis of autoimmune diseases. Here, we review the
      current knowledge on iNKT cell biology and focus our attention on the possible
      mechanism of action and final effect of the different iNKT cell subsets in the
      pathogenesis of T cell-mediated autoimmune diseases. 

PMID- 24896349
TI  - Neuronal pathways in tendon healing and tendinopathy--update.
AB  - The regulatory mechanisms involved in tendon homeostasis and repair are not fully
      understood. Accumulating data, however, demonstrate that the nervous system, in
      addition to afferent (sensory) functions, through efferent pathways plays an
      active role in regulating pain, inflammation, and tissue repair. In normal-,
      healing- and tendinopathic tendons three neurosignalling pathways consisting of
      autonomic, sensory and glutamatergic neuromediators have been established. In
      healthy tendons, neuromediators are found in the paratenon, whereas the proper
      tendon is practically devoid of nerves, reflecting that normal tendon homeostasis
      is regulated by pro- and anti-inflammatory mediators from the tendon
      surroundings. During tendon repair, however, there is extensive nerve ingrowth
      into the tendon proper and subsequent time-dependent appearance of sensory,
      autonomic and glutamatergic mediators, which amplify and fine-tune inflammation
      and tendon regeneration. In tendinopathy, excessive and protracted sensory and
      glutamatergic signalling may be involved in inflammatory, painful and
      hypertrophic tissue reactions. As our understanding of these processes improves,
      neuronal mediators may prove to be useful in the development of targeted
      pharmacotherapy and tissue engineering approaches to painful, degenerative and
      traumatic tendon disorders. 

PMID- 24896350
TI  - Role of IFN-gamma in immune responses to Candida albicans infections.
AB  - Candida albicans is the most frequent etiologic agent that causes opportunistic
      fungal infections called candidiasis, a disease whose systemic manifestation
      could prove fatal and whose incidence is increasing as a result of an expanding
      immunocompromised population. Here we review the role of interferon-gamma (IFN
      gamma) in host protection against invasive candidiasis. This cytokine plays an
      essential role in both the innate and adaptive arms of the immune response to
      candidiasis. We focus on recent progress on host-pathogen interactions leading to
      the production of IFN-gamma by host cells. IFN-gamma is produced by CD4 Th1, CD8,
      gamma delta T, and natural killer (NK) cells, essentially in response to both IL
      12 and/or IL-18; more recently, a subset of C. albicans -specific Th17 cells have
      been described to produce both IL-17 and IFN-gamma. IFN-gamma plays an important
      role in the regulation of the immune system as well as in the control of the
      infectious process, as it is required for optimal activation of phagocytes,
      collaborates in the generation of protective antibody response, and favors the
      development of a Th1 protective response. 

PMID- 24896351
TI  - Neuronal oscillations in Parkinson's disease.
AB  - Parkinson's Disease (PD), characterized by tremor, rigidity, and bradykinesia, is
      one of the most prevalent neurodegenerative disorders in the world. The
      pathological hallmark of PD is the loss of dopaminergic cells in the substantia
      nigra and other brain regions. The pathophysiological mechanisms by which
      dopaminergic cell loss leads to the motor manifestations of PD are yet to be
      fully elucidated. A growing body of evidence has revealed abnormal neuronal
      oscillations within and between multiple brain regions in PD. Unique oscillatory
      patterns are associated with specific motor abnormalities in PD. Therapies, such
      as dopaminergic medication and deep brain stimulation that disrupt these abnormal
      neuronal oscillatory patterns produce symptomatic improvement in PD patients.
      These findings emphasize the importance of abnormal neuronal oscillations in the
      pathophysiology of PD, making the disruption of these oscillatory patterns a
      promising target in the development of effective PD treatments. 

PMID- 24896352
TI  - Calorie restriction and NAD+/sirtuin counteract the hallmarks of aging.
AB  - Among diverse environmental factors that modify aging, diet has a profound
      effect. Calorie restriction (CR), which entails reduced calorie consumption
      without malnutrition, is the only natural regimen shown to extend maximum and
      mean lifespan, as well as healthspan in a wide range of organisms. Although the
      knowledge about the biological mechanisms underlying CR is still incipient,
      various approaches in biogerontology research suggest that CR can ameliorate
      hallmarks of aging at the cellular level including telomere erosion, epigenetic
      alterations, stem cells depletion, cellular senescence, mitochondrial
      dysfunction, genomic instability, proteostasis imbalance, impaired nutrient
      sensing and abnormal intercellular communication. Currently, the NAD + /sirtuin
      pathway is one of the few mechanisms described to mediate CR effects and sirtuin
      activating compounds (STACs) mimic many effects of CR. Herein, we discuss the
      effects of CR on healthspan with emphasis on neuroprotection, how CR counteracts
      cellular aging, how sirtuin pathways intertwine with CR, and the relevance of
      STACs in mimicking CR effects. 

PMID- 24896353
TI  - Gold nanoparticles: various methods of synthesis and antibacterial applications.
AB  - Colloidal gold is very attractive for several applications in biotechnology
      because of its unique physical and chemical properties. Many different synthesis
      methods have been developed to generate gold nanoparticles (AuNPs). Here, we will
      introduce these methods and discuss the differences between fabrication
      techniques. We will also discuss ecofriendly synthesis methods being developed to
      efficiently generate AuNPs without the use of toxic substrates. Finally, we will
      discuss the medical applications for AuNPs by highlighting the potential use of
      intact or functionalized AuNPs in combating bacterial infections. 

PMID- 24896354
TI  - An update on drug treatment options of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by progressive decrease in cognitive
      function and loss of short-term memory known to be associated with a dysfunction
      of the cholinergic system. The pathological hallmarks of AD are beta-amyloid
      (Abeta) plaques and neurofibrillary tangles (NFTs) consisting of
      hyperphosphorylated tau. Hypercholesterolemia and disturbances in glucose
      metabolism are another risk factors. During the last two decades therapeutic
      strategies were mainly targeting the Abeta hypothesis. As this approach virtually
      failed to show a significant clinical benefit research on potential therapeutics
      has been shifted to tau pathology. However, also this approach has as yet not
      yielded in new therapeutics. Hence, rebalancing the cholinergic input to improve
      the cognitive symptoms of AD by inhibition of acetylcholine esterase (AChE) is
      still the only mechanistic target in addition to N-methyl-D-aspartate (NMDA)
      receptor blockade by memantine that can be addressed by currently approved
      medications. Despite the fact that the available AChE inhibitors are directed at
      an identical target they exhibit some pharmacodynamic and pharmacokinetic
      features that should be considered when used clinically. 

PMID- 24896356
TI  - Deregulation of T cell response in sepsis.
AB  - The development of sepsis invovles the dysfunction of immunity due to an
      imbalance between the hyperimmune response and the immunoparalysis. Immune cells
      in both the innate and acquired immune system, including neutrophils,
      macrophages, dendritic cells, T cells and NK cells, are actively involved in the
      process. The interaction between immune cells, proinflammatory and anti
      inflammatory cytokines contribute to the immunoparalysis in sepsis. Abnormal CD4+
      and CD8+ T cell responses are major components of the deregulated acquired immune
      response in sepsis. Immune dysfunction of regulatory T cells (Tregs) contributes
      to the pathogensis of sepsis. Furthermore, IL-7 is essential for the
      replenishment and survival of T cells, which represents a promising target for
      immunotherapy of sepsis. In this review, we discusse the the immunoparalysis in
      the sepsis, with a focus on the deregulation of T cell response. 

PMID- 24896355
TI  - Regulation of cystathionine gamma-lyase/H2S system and its pathological
      implication.
AB  - Hydrogen sulfide (H2S) is a highly diffusible gasotransmitter, that influence
      cellular and organ functions by a number of different mechanisms. Cystathionine
      gamma-lyase (CSE) is one major H2S-producing enzyme with L-cysteine as the main
      substrate in mammalian cells. Since the discovery of endogenously-produced H2S as
      a biological mediator, there has been an explosion of interest in CSE expression
      and regulation. CSE expression and activity and ultimately the amount of H2S
      synthesis is controlled by a complex integration of transcriptional, post
      transcriptional and post-translational mechanisms. Considering the key role that
      CSE/H 2 S system plays in both health and diseases, a better understanding of the
      regulation of CSE/H 2 S system will help us to develop novel and more effective
      strategies to target CSE and alter H2S production inside cells. In this review,
      we summarize the altered expression and activity of CSE and abnormal H2S
      production in various pathophysiological conditions. The current knowledge on the
      signaling and regulatory pathways for CSE expression and H2S production are also
      elucidated. As such, our understanding of the pathogenesis of human diseases will
      be better achieved and the corresponding new therapy can be devised. 

PMID- 24896357
TI  - Evaluation of hepatic steatosis using dual-energy CT with MR comparison.
AB  - In this study, we aimed to explore the potential of dual-energy computed
      tomography (DECT) in evaluating liver fat; we also compared the diagnostic
      performance of DECT, T1-weighted dual-echo magnetic resonance (MR) imaging, and
      1H-MR spectroscopy (1H-MRS) in assessing hepatic steatosis in a fatty liver rat
      model. Fat (water) concentration measurements by DECT spectral imaging, MR
      findings, and 1H-MRS measurements of hepatic fat showed similar correlations with
      the histopathologic results. Furthermore, a good correlation was observed between
      the fat (water) concentration and 1H-MRS measurements (r = 0.800 and P less than
      0.001). The discriminant accuracies of the fat (water) concentration, MR
      findings, and 1H-MRS measurements were 66.7, 64, and 56 percent, respectively.
      Therefore, we conclude that the findings of DECT spectral CT imaging are strongly
      correlated with histopathologic findings in cases of steatosis; in addition, DECT
      can allow rapid, accurate evaluations of hepatic steatosis that are as effective
      as those obtained using T1-weighted dual-echo MR imaging and 1H-MRS. 

PMID- 24896359
TI  - Simulation model for combined motion of myosin cross-bridges agrees with
      experimental data.
AB  - The motivation for this work was to derive a theoretical model for the combined
      motion of a sample of muscle tissue with a small number (approximately 12) of
      myosin molecules. This was then compared to data collected at the University of
      North Texas Health Science center. A theoretical model of the motion of the
      myosin cross-bridges has been derived. The solution is a combination of solutions
      from the classical harmonic oscillator, Brownian motion, and Maxwell-Boltzmann
      statistics. The model illustrates the myosin behavior as a function of the number
      of myosin molecules, the temperature of the sample, and the spring constant. The
      results show that there is good agreement between the theoretical model and
      experimental data. 

PMID- 24896358
TI  - Id transcriptional regulators in adipogenesis and adipose tissue metabolism.
AB  - Id proteins (Id1-Id4) are helix-loop-helix (HLH) transcriptional regulators that
      lack a basic DNA binding domain. They act as negative regulators of basic helix
      loop-helix (bHLH) transcription factors by forming heterodimers and inhibit their
      DNA binding and transcriptional activity. Id proteins are implicated in the
      regulation of various cellular mechanisms such as cell proliferation, cellular
      differentiation, cell fate determination, angiogenesis and tumorigenesis. A
      handful of recent studies also disclosed that Id proteins have critical functions
      in adipocyte differentiation and adipose tissue metabolism. Here, we reviewed the
      progress made thus far in understanding the specific functions of Id proteins in
      adipose tissue differentiation and metabolism. In addition to reviewing the known
      mechanisms of action, we also discuss possible additional mechanisms in which Id
      proteins might participate in regulating adipogenic and metabolic pathways.

PMID- 24896360
TI  - The dual role of ERK signaling in the apoptosis of neurons.
AB  - The extracellular signal-regulated kinase (ERK) signaling pathway participates in
      various cell responses, such as proliferation, migration, differentiation and
      death. In neuronal apoptosis, the ERK pathway has been shown to have a dual role.
      Although the majority of studies have demonstrated the ERK pathway to have an
      anti-apoptotic role in neurons, pro-apoptosis induced by ERK signaling, has also
      been observed. The different effects of the ERK pathway may be due to the
      different kinds of neurons used in these studies, stimulus, interplay with other
      MAPK pathways and maybe other as yet unclear factors. In this review, we will
      summarize the role of the ERK signaling pathway in the apoptosis of neurons. 

PMID- 24896361
TI  - MicroRNA in hepatic fibrosis and cirrhosis.
AB  - Hepatic fibrosis is caused by an imbalance between production and dissolution of
      extracellular matrix after chronic and inflmmatory injury, when hepatic stellate
      cells are stimulated to proliferate and secret extracellular matrix. The most
      common causes of liver fibrosis are chronic viral hepatitis B and C. Cirrhosis is
      the most advanced stage of fibrosis, which usually develop into hepatocellular
      carcinoma (HCC). microRNAs participate the pathogenesis of hepatic fibrosis and
      cirrhosis or even the onset of HCC. In this review, we will summarize the role of
      miRNA in the pathogenesis of viral hepatitis fibrosis, non-alcoholic
      steatohepatitis fibrosis, primary biliary cirrhosis and HCC onset, especially in
      the regulation of stellate cells. 

PMID- 24896362
TI  - ABC-transporters as stem-cell markers in brain dysplasia/tumor epilepsies.
AB  - ABC-transporters prevent the access of antiepileptic drugs into brain parenchyma,
      which partly explains why seizures are frequently refractory to AEDs treatment.
      Overexpression of ABC-transporters and stem-cell markers including CD34, have
      been detected in malformations of cortical development (MCD) and brain tumors.
      ABC-transporters are constitutively expressed during maturation of normal
      progenitor stem-cells and cancer stem-cells. These abnormal/immature cells of MCD
      or brain tumors play an active role in the epileptogenesis but the precise nature
      of this phenomenon is unclear. Irrespective of their property in the
      pharmacoresistance, ABCB1-transporter P-glycoprotein also plays a role in the
      membrane depolarization, suggesting that constitutive P-glycprotein
      overexpression in MCD and brain tumors could explain their epileptogeneic
      properties. MCD as wells as brain tumors arise from abnormal progenitor cells,
      where ABC-t together with others stem cell markers, could help to better
      identification of these abnormal progenitor cells and serve as biomarker of risk
      for seizure relapse after epilepsy surgery. 

PMID- 24896363
TI  - Synthesis and degradation of poly(ADP-ribose) in plants.
AB  - Poly(ADP-ribosylation) is a post-translational modification of proteins involved
      in a wide range of molecular and cellular processes in mammalian system. The main
      enzymes responsible for this modification are the poly(ADP-ribose) polymerases
      that catalyze the transfer of ADP-ribose moieties from NAD + to target protein
      acceptors, producing long and branched ADP-ribose polymers. The poly(ADP
      ribosyl)ation is rapidly reverted by poly(ADP-ribose) glycohydrolase enzymes,
      which hydrolyzes poly(ADP-ribose) polymers, generating free ADP-ribose. So far,
      nine proteins with a poly(ADP-ribose) polymerase signature and two poly(ADP
      ribose) glycohydrolase enzymes encoded by two adiacent genes were identified in
      Arabidopsis . The present review will describe the structures and functions of
      plant poly(ADP-ribose) polymerases and poly(ADP-ribose) glycohydrolases. 

PMID- 24896364
TI  - From neurogenesis to neuroprotection in the epilepsy: signalling by
      erythropoietin.
AB  - Epilepsy is a disorder characterised by recurrent seizures and molecular events,
      including the activation of early expression genes and the post-translational
      modifications of functional proteins. These events lead to changes in
      neurogenesis, mossy fibre sprouting, network reorganisation and neuronal death.
      The role of these events is currently a matter of great debate, especially as
      they relate to protection, repair, or further brain injury. In recent years,
      accumulating data have supported the idea that erythropoietin (EPO) regulates
      biological processes including neuroprotection and neurogenesis in several
      diseases, such as epilepsy. This review summarises the role of EPO in some of the
      molecular mechanisms involved in these events that could direct a more detailed
      approach for its use as a therapeutic alternative in reducing epileptic seizures.

PMID- 24896366
TI  - Withdrawal of repeated morphine enhances histamine-induced scratching responses
      in mice.
AB  - An itch is experientially well known that the scratching response of conditions
      such as atopic dermatitis is enhanced under psychological stress. Morphine is
      typical narcotic drug that induces a scratching response upon local application
      as an adverse drug reaction. Although long-term treatment with morphine will
      cause tolerance and dependence, morphine withdrawal can cause psychologically and
      physiologically stressful changes in humans. In this study, we evaluated the
      effects of morphine withdrawal on histamine-induced scratching behavior in mice.
      Administration of morphine with progressively increasing doses (10-50 mg/kg,
      i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after
      spontaneous withdrawal from the final morphine dose, histamine was intradermally
      injected into the rostral part of the back and then the number of bouts of
      scratching in 60 min was recorded and summed. We found that at 24 hr after
      morphine withdrawal there was a significant increase in histamine-induced
      scratching behavior. The spinal c-Fos positive cells were also significantly
      increased. The relative adrenal weight increased and the relative thymus weight
      decreased, both significantly. Moreover, the plasma corticosterone levels changed
      in parallel with the number of scratching bouts. These results suggest that
      morphine withdrawal induces a stressed state and enhances in histamine-induced
      scratching behavior. Increased reaction against histamine in the cervical
      vertebrae will participate in this stress-induced itch enhancement. 

PMID- 24896365
TI  - ADAMTS-18: a metalloproteinase with multiple functions.
AB  - ADAMTS-18 is a member of a disintegrin and metalloproteinase with thrombospondin
      motifs (ADAMTS) family of proteases, which are known to play important roles in
      development, angiogenesis and coagulation; dysregulation and mutation of these
      enzymes have been implicated in many disease processes, such as inflammation,
      cancer, arthritis and atherosclerosis. Mutations of ADAMTS-18 have been linked to
      abnormal early eye development and reduced bone mineral density. In this review,
      we briefly summarize the structural organization and the expression of ADAMTS-18.
      We will also focus on the emerging role of ADAMTS-18 in several
      pathophysiological conditions which include: hematological diseases,
      tumorgenesis, osteogenesis, eye-related diseases, central nervous system
      disorders, and last but not least a research perspective of ADAMTS-18 and its
      potential as a promising diagnostic and therapeutic target. 

PMID- 24896367
TI  - 17alpha-Estradiol down-regulates glutathione synthesis in serum deprived PC-12
      cells.
AB  - During the last decades it has been shown that estrogen may have neuroprotective
      functions in the CNS. However, we have previously reported that pretreatment with
      estradiol abolishes its protection of cultured cerebellar granule neurons from
      glutamate-induced cell death due to down-regulation of endogenous glutathione.
      17alpha-Estradiol is considered a hormonally inactive isomer of 17beta-estradiol
      still containing its antioxidant potential. Here, we demonstrate that 17alpha
      estradiol enhanced serum deprivation-induced cell death in the rat
      pheochromocytoma cell line PC-12, while antioxidants vitamins C and E in
      combination (vitamins C/E) tended to protect. We further examined mechanisms
      behind the glutathione lowering effect of 17alpha-estradiol in serum deprived PC
      12 cells. Endogenous glutathione levels were reduced in the serum deprived cells.
      Serum deprivation-induced cell death seemed to depend partly on this reduction as
      supplemented N-acetylcysteine, a cysteine precursor with potential to restore
      glutathione levels, reduced cell death. 17alpha-Estradiol down-regulated
      glutathione, promoter activity of the rate-limiting enzyme in glutathione
      production, glutamate cysteine ligase (GCL), as well as c-Fos protein levels in
      serum deprived cells. The c-Fos transcription factor normally binds to the AP-1
      response element in the GCL promoter resulting in increased production of
      glutathione as a stress response. Over-expression of AP-1 proteins partly
      restored the GCL promoter activity in serum deprived cells treated with 17alpha
      estradiol. Nrf2, a transcription factor binding another response element in the
      GCL promoter was unaffected by 17alpha-estradiol. Conclusively, 17alpha-estradiol
      may have a long-term negative effect on the endogenous glutathione level through
      its ability to down-regulate the glutathione synthesis during serum deprivation.

PMID- 24896368
TI  - Interventions for treating phosphorus burns.
AB  - BACKGROUND: Phosphorus burns are rarely encountered in usual clinical practice
      and occur mostly in military and industrial settings. However, these burns can be
      fatal, even with minimal burn area, and are often associated with prolonged
      hospitalisation. OBJECTIVES: To summarise the evidence of effects (beneficial and
      harmful) of all interventions for treating people with phosphorus burns. SEARCH
      METHODS: In October 2013 for this first update we searched the Cochrane Wounds
      Group Specialised Register; the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library);Ovid OLDMEDLINE; Ovid MEDLINE; Ovid MEDLINE (In
      Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL and Conference
      Proceedings Citation Index - Science (CPCI-S). We did not apply any
      methodological filters or restrictions on the basis of study design, language,
      date of publication or publication status. SELECTION CRITERIA: Any comparisons of
      different ways of managing phosphorus burns including, but not restricted, to
      randomised trials. DATA COLLECTION AND ANALYSIS: We found two non-randomised
      comparative studies, both comparing patients treated with and without copper
      sulphate. MAIN RESULTS: These two comparative studies provide no evidence to
      support the use of copper sulphate in managing phosphorus burns. Indeed the small
      amount of available evidence suggests that it may be harmful. AUTHORS'
      CONCLUSIONS: First aid for phosphorus burns involves the common sense measures of
      acting promptly to remove the patient's clothes, irrigating the wound(s) with
      water or saline continuously, and removing phosphorus particles. There is no
      evidence that using copper sulphate to assist visualisation of phosphorus
      particles for removal is associated with better outcome, and some evidence that
      systemic absorption of copper sulphate may be harmful. We have so far been unable
      to identify any other comparisons relevant to informing other aspects of the care
      of patients with phosphorus burns. Future versions of this review will take
      account of information in articles published in languages other than English,
      which may contain additional evidence based on treatment comparisons.

PMID- 24896369
TI  - The administration of L-thyroxine as soft gel capsule or liquid solution.
AB  - INTRODUCTION: Levothyroxine (l-T4) is the mainstay of treating hypothyroidism.
      The tablet is the traditional formulation of l-T4. Tablet l-T4 malabsorption
      results from either hindered gastric dissolution of the tablet or binding of l-T4
      by sequestrants in the intestinal lumen. AREAS COVERED: This review provides an
      overview of the pharmacokinetics of l-T4 formulations available in the market:
      the tablet, the soft gel capsule and the oral solution. We review literature on
      the new formulations and anticipate the areas of future research. EXPERT OPINION:
      Failure of l-T4 treatment to reach target serum thyroid-stimulating hormone
      levels generally prompts the physicians to increase l-T4 daily dose. In vitro
      studies have shown that the soft gel capsule releases the active ingredient more
      consistently at varying pH than the tablet. In addition, in vivo studies have
      confirmed the in vitro data and have demonstrated that both the soft gel capsule
      and the liquid formulation are capable to solve tablet l-T4 malabsorption caused
      by certain drugs, bariatric surgery or coffee. These new formulations may be
      attractive also for patients who cannot/do not want to change their (improper)
      habits of l-T4 ingestion. Finally, the oral solution l-T4 could be suitable for
      patients who cannot swallow the solid formulations.

PMID- 24896370
TI  - The response of a (3)He Fermi liquid droplet to vibronic excitation of an
      embedded glyoxal molecule.
AB  - The zero-phonon line (ZPL) and the sideband in the vibronic spectrum of a single
      glyoxal molecule inside a (3)He droplet are analyzed within the framework of the
      Lax formalism. The new theory takes full account of the coupling of the molecule
      to the single particle-hole (PH) and collective excitations of the doped
      Fermionic droplet. The effect on the coupling of the wavevector dependence of the
      effective (3)He mass and the large local density of the first (3)He shell,
      resulting from the interaction with the chromophore, are also included in the
      theory. By fitting of a coupling parameter and the phase factor between the PH
      and collective response functions, the shape and relative intensity of the
      observed ZPL and its slowly decreasing multiexcitation sideband are well
      reproduced. The new theory is consistent with the previous explanation of the
      surprisingly sharp phonon line superimposed on the sideband in terms of the dense
      first (3)He shell, which acts as a Helmholtz resonator for the zero sound of the
      droplet. 

PMID- 24896371
TI  - Catalytic asymmetric 1,3-dipolar [3 + 6] cycloaddition of azomethine ylides with
      2-acyl cycloheptatrienes: efficient construction of bridged heterocycles bearing
      piperidine moiety.
AB  - Conjugated cyclic trienes without nonbenzenoid aromatic characteristic were
      successfully employed as fine-tunable dipolarophiles in the Cu(I)-catalyzed
      asymmetric azomethine ylide-involved 1,3-dipolar [3 + 6] cycloaddition for the
      first time, affording a variety of bridged heterocycles bearing piperidine moiety
      in good yield with exclusive regioselectivity and excellent stereoselectivity. 2
      Acyl group is the key factor that determines the annulation preferentially
      through [3 + 6]-pathway, while 2-ester group modulates the annulation through [3
      + 2]-pathway. 

PMID- 24896372
TI  - Modified lactic acid bacteria detect and inhibit multiresistant enterococci.
AB  - We designed Lactococcus lactis to detect Enterococcus faecalis. Upon detection,
      L. lactis produce and secrete antienterococcal peptides. The peptides inhibit
      enterococcal growth and reduce viability of enterococci in the vicinity of L.
      lactis. The enterococcal sex pheromone cCF10 serves as the signal for detection.
      Expression vectors derived from pCF10, a cCF10-responsive E. faecalis sex
      pheromone conjugative plasmid, were engineered in L. lactis for the detection
      system. Recombinant host strains were engineered to express genes for three
      bacteriocins, enterocin A, hiracin JM79 and enterocin P, each with potent
      antimicrobial activity against E. faecalis. Sensitive detection and specific
      inhibition occur both in agar and liquid media. The engineered L. lactis also
      inhibited growth of multidrug-resistant E. faecium strains, when induced by
      cCF10. The presented vectors and strains can be components of a toolbox for the
      development of alternative antibiotic technologies targeting enterococci at the
      site of infection.

PMID- 24896375
TI  - Effects of non-contact exposure to rodents on defensive behaviors in mice.
AB  - These experiments explored the effects of non-contact exposure to two rodent
      species (rats and gerbils) on the defensive behaviors of male CD-1 mice. In
      Experiment 1 it was found that rats evoked substantial levels of defensiveness
      which were positively related to increases in rat activity. This effect was
      considerably attenuated, but still detectable, 30 min after rat exposure
      (Experiment 2). In Experiment 3 the effectiveness of rats and gerbils were
      compared. Gerbils were found to evoke a more modest increase in defensiveness
      than rats. These experiments indicate that non-contact exposure to rodents
      displaying varying levels of activity and, perhaps, propensity for predatory
      behavior provide a useful level of experimental control over the intensity of
      fear-like responses. 

PMID- 24896373
TI  - Two new eunicellin-based diterpenoids from the South China Sea gorgonian
      Muricella sibogae Nutting.
AB  - Two new eunicellin-based diterpenoids, sibogins A (1) and B (2), along with one
      known analogue (3), and four known 9,10-secosteroids (4-7), were isolated from
      the gorgonian Muricella sibogae Nutting collected from the South China Sea. The
      structures of the new compounds were elucidated by comprehensive analysis of
      spectroscopic data, especially by using 2D NMR spectra. The antifouling activity
      on barnacle Balanus amphitrite and lethality towards brine shrimp Artemia salina
      of all the isolated compounds were evaluated.

PMID- 24896374
TI  - Does father know best? Social learning from kin and non-kin in juvenile
      ringdoves.
AB  - Parent-offspring transmission is usually thought to be the major route for
      cultural learning. We tested this assumption in ringdoves (Streptopelia risoria),
      a flock feeding Columbid that is easily raised in captivity. An aviary study
      first determined the foraging associations of juveniles placed with their
      sibling, their parents and a pair of non-kin adults. Juveniles foraged more often
      with kin than with non-kin and joined food discoveries in proportion to these
      foraging associations; aggression was relatively rare and came more often from
      unrelated adults than from parents. Two cage experiments showed that parents were
      not copied more often than unrelated adults when the two tutor types provided
      different, but equally productive, solutions to a feeding problem. Neither the
      ingestion of unfamiliar food (two seed types the juveniles had never encountered)
      nor the learning of a new food searching skill (opening a box containing seed)
      showed a differential effect of father versus non-kin tutors. Animals that
      scramble compete for food may thus acquire social information from whatever
      knowledgeable individuals are present, whether these are kin, unrelated
      conspecifics or heterospecifics. 

PMID- 24896376
TI  - Further data on conflict behaviour in golden hamsters: shifting between
      alternative sets of directional information.
AB  - Golden hamsters were trained to collect food in two differently patterned test
      boxes, linked to each other and to the nest by a T-shaped tube. To choose the
      correct goal direction from each box entrance the subjects could use either
      locomotor or visual cues. In test trials the central arm of the T-tube and the
      nest were rotated by 180 degrees , setting visual and locomotor information in
      conflict. For one group of subjects, only the boxes were illuminated, whereas for
      a second group a general visual background was added. Locomotor information
      prevailed over visual for the majority of group 1 subjects. The second group gave
      the same weight to locomotor and visual cues in choosing the initial direction,
      but again depended more on locomotor cues for their final orientation. In a
      complementary test using the group 1 subjects, the hamsters entered the test box
      directly (without passing through the T-tube) and were therefore deprived of
      learned locomotor cues. Most animals chose the visually correct goal, showing
      that they had also associated the food locations with the visual cues. The
      experimental set-up favoured conflict resolution by shifting between locomotor
      and visual cues rather than by choosing compromise directions. This suggests that
      both kinds of information were processed simultaneously but could be used
      successively throughout each hoarding excursion. 

PMID- 24896377
TI  - Group foraging in snowshoe hares (Lepus americanus): Aggregation or social group?
AB  - We investigated the behavioural mechanisms involved in group formation at a
      feeding site in a captive snowshoe hare population. The analysis showed that
      grouping resulted most often from a feeding attraction which led individuals to
      use the feeding site independently of each other. However social attraction and
      especially social repulsion among hares were also involved in group size
      dynamics. As group size increased, social repulsion underlined by an
      autocatalytic process led the hares to collectively leave the feeding site.
      Consequently, the social interactions rates and distance covered per hare
      increased non-linearly with hare number present at the feeding site. The results
      suggest that hare behaviour underlined by these mechanisms may influence the
      risks of starvation and predation. From these results, further field studies are
      suggested to test in the framework of a multi-factor hypothesis how hare
      behaviour, food supply and predation may interact simultaneously in population
      regulation. 

PMID- 24896379
TI  - The effect of blood signals on aggressive behaviour in mice.
AB  - The study examined whether blood applied to the coat of a male opponent mouse
      modifies the aggressive behaviour of the attacking male mouse. Interest was also
      focused on whether the signal value of blood is related to the location of
      different bite targets, and whether such communication is visually or olfactorily
      mediated. The subjects used in the study were male Turku Aggressive (TA) mice of
      the 57th generation of selection for high levels of aggressiveness. The 72 TA
      males were divided into six groups matched on the times of latency to the first
      attack in standard dyadic aggression tests. Different groups of male TA mice were
      tested against opponents with blood, a red solution or nothing applied to either
      both flanks or the forehead. Testing was discontinued after the first attack. The
      results showed that blood had an inhibiting effect on aggression unrelated to the
      location of its application. The opponents with blood applied to their coats were
      attacked significantly later and the TA males sniffed such opponents
      significantly more. Odours associated with blood presumably serve as signalling
      pheromones. The biological significance of blood signals is discussed. 

PMID- 24896378
TI  - Ritualised versus aggressive behaviours displayed by Polyrhachis laboriosa (F.
      Smith) during intraspecific competition.
AB  - The intraspecific territoriality of Polyrhachis laboriosa was studied thanks to
      dyadic confrontations between nestmates and alien foragers in chemically marked
      and unmarked arenas, complementing experiments and observations in nature. When
      foragers meet, the alien flees while the resident attacks, especially when on a
      marked area. However, when an alien scout extends its territory, it attacks the
      resident ant, such confrontation resulting in a high rate of reciprocal full
      attacks. When surrounded by several residents, the intruder is always spread
      eagled if it does not succeed in fleeing. We described ritualised displays, such
      as threatening (opening mandibles; bending the gaster) or appeasing behaviours
      (antennal boxing; attempt at trophallaxis; pupal posture; raising the gaster).
      They occur only when the encounter maintains a low level of aggression, during
      laboratory experiments, or in nature during encounters involving a queen or an
      experimentally-introduced intruder. Foraging queens are tolerated on the
      territories of conspecific mature colonies. When they encounter resident workers,
      reciprocal avoidance occurs. Nevertheless, the latter perform ritualised displays
      when the queens approach their nest or attempt to rob their prey. This situation
      seems to compensate in part the archaic semi-claustral mode of foundation of this
      species, as the queens are indirectly protected by their conspecifics who do not
      tolerate other competitors around large food sources. 

PMID- 24896380
TI  - Seasonal use and selection of habitat by mouflon (Ovis gmelini):Comparison of the
      sexes.
AB  - We studied seasonal habitat use of female, mixed-sex and male groups in a free
      ranging mouflon (Ovis gmelini) population. The three group types differed in the
      use of the five different habitats (forests, broom moorlands, heather moorlands,
      meadows and rocky areas) only in spring (lambing period) and in autumn (rutting
      period). To study habitat selection, we compared the proportion of groups
      observed in each habitat type with the proportion of each of these habitat types
      sampled. This revealed that, for the four seasons, all three group types selected
      certain habitats. Overall, mouflon selected meadows and/or broom moorlands, but
      male groups switched to forests in spring and autumn. We examined this pattern of
      habitat selection in relation to shelter value and feeding activity for the three
      group types. Wind strength played a role in determining patterns of habitat use
      during the climatic extremes of winter and summer. Male and female groups
      consistently fed in the same habitat types, even though they did not select the
      same habitats in spring and autumn and despite a marked segregation between the
      sexes in this population. Two commonly cited hypothesis for explaining sexual
      segregation based on sexual size dimorphism and on alternative reproductive
      strategies of males and females were not supported by our results. We suggest
      that simple behavioural mechanisms may suffice to explain sexual segregation in
      this population. 

PMID- 24896381
TI  - The effect of demonstrator age and number on duration of socially-induced food
      preferences in house mouse (Mus domesticus).
AB  - Present research was undertaken to investigate whether the transfer of food
      preference from a demonstrator mouse to an observer can be influenced by their
      relative age. In experiment 1 an adult female mouse, the observer, was allowed to
      interact with a recently-fed demonstrator which was a pup of her litter or an
      adult female mouse. The observer was then tested to assess whether it acquired a
      preference for the demonstrator's diet. The results showed that a pup
      demonstrator's influence on an adult's food preference is shorter-lasting than an
      adult demonstrator's influence. Experiment 2 was aimed to investigate whether
      many demonstrators have an additive effect in influencing their observer's
      choice. The results indicated that multiple pup demonstrations do not increase
      longevity of food preferences induced by pup demonstrators. Moreover, the
      longevity of an adult observer's preference for its demonstrator's food is
      reduced by the exposure to multiple adult demonstrators. Results are discussed in
      terms of demonstrator's reliability and of social constraints that could affect
      social transfer of food information in the house mouse. 

PMID- 24896382
TI  - Resolution of agonistic conflicts in dyads of acquainted green swordtails
      (Xiphophorus helleri): a game with perfect information.
AB  - Conflict resolution of acquainted opponents was compared to that of unacquainted
      ones in Xiphophorus helleri males. Under the Familiar condition, the 2 males
      which met had settled contest against each other in a previously staged encounter
      in another aquarium. Thus one opponent was previously the dominant pair member,
      the other its subordinate. Under the Unfamiliar condition, 2 males met which were
      not acquainted with each other but had independently undergone previous
      experience of victory or defeat. We tested the hypothesis that familiar pairs
      would conform to some behavioural predictions of an asymmetrical game with
      perfect information. As for unfamiliar pairs, being imperfectly informed of
      asymmetries at contest onset, they would have to acquire information on these
      during the course of interaction (asymmetrical game with assessment) or
      alternatively would have to persist for a certain time or cost (war of
      attrition). All expectations derived from an asymmetrical game with perfect
      information applied to familiar pairs but not to unfamiliar ones. In familiar
      pairs, all previous roles were reinstated without any escalation. Though previous
      winners predominantly defeated previous losers under both conditions of
      cognizance, this difference was more extreme in familiar dyads than in unfamiliar
      ones. This suggests that the respective roles were less clearly identified in the
      latter. The costs of conflicts, both in terms of aggressive behaviours used and
      in time, were also higher in unfamiliar pairs than in familiar ones. Unacquainted
      individuals required a longer period to assess each other. In addition, they had
      to rely on more pugnacious behaviour to settle disputes in comparison to
      acquainted pairs. As expected also, familiar pairs being already cognizant of
      initial respective roles were more characterized in terms of the behavioural
      patterns typical of each of these roles. Differences between ultimate winners and
      losers were clearer in acquainted pairs and appeared earlier during conflict. It
      was also possible earlier during contest to discriminate and predict ultimate
      winners from losers of acquainted pairs using behavioural interactions. In
      unacquainted pairs, ultimate winners could be forecasted using multivariate
      discriminant analyses, mainly by their offering resistance to future losers. A
      'war of attrition' did not fit to unacquainted pairs. 

PMID- 24896383
TI  - Observational learning of duration discrimination in rats (Rattus norvegicus).
AB  - Hungry 'observer' rats watched at trained conspecific 'demonstrators' performing
      a duration discrimination (1 vs. 8 s sound) before being themselves exposed to
      the same task. Performance of 'observer' rats was compared with that of naive
      control rats who learned the same task without observing a demonstrator.
      Statistical analysis showed that observing a trained demonstrator significantly
      contributed to the rapid discovery of the relationship between a particular
      duration and its related response patterns or stimuli, increasing learning speed
      with regard to the control animals. 

PMID- 24896384
TI  - Behavioural processes - The first three years.

PMID- 24896385
TI  - On the function of the 'eye-spots' in agonistic behaviour in the fire-mouth
      cichlid (Cichlasoma Meeki).
AB  - During frontal threatening, individuals of the fire-mouth cichlid (Cichlasoma
      meeki) dilate their opercula, thereby demonstrating two conspicous 'eye-spots'.
      In a hostile situation, a fish confronted with an opponent whose eye-spots have
      been experimentally removed is more likely to react with overt aggression towards
      the other. Fights also follow a more violent course than does a 'normal' fight
      between two intact males. A tentative explanation to these results is advanced
      which supposes that the eye-spots may exert an 'intimidating' effect upon the
      opponent during threat and fighting. This hypothesis is also supported by an
      experiment where males were confronted with a mirror. In this situation the
      distance between the mirror and the fish during frontal threat was significantly
      shorter in fishes lacking eye-spots, indicating that the intimidating effect
      emerging from the mirror image was diminished. In a third set of experiments when
      two males (one intact and one without eye-spots) competed for the only suitable
      territory site in an aquarium, the intact male eventually dominated the other in
      five of six aquariums. 

PMID- 24896386
TI  - Peeping and attachment to visual and auditory stimuli in day-old chicks.
AB  - The usefulness of peeping in indexing attachment to visual and auditory stimuli
      was confirmed in chicks between 18 and 30 h post-hatch. Greater attractiveness of
      the auditory stimulus was associated with a more marked initial reduction in
      peeping after auditory stimulus presentation, suggesting a greater attentional
      impact, and with greater effectiveness in reducing peeping during repeated
      stimulus presentations. There was no difference between the two stimuli in
      effects on peeping before or shortly after the initial approach to the stimuli.
      Of additional interest was the observation of a sharp rise in peeping immediately
      preceding the increased activity associated with initial approach. The possible
      relationship between peeping and arousal was considered. 

PMID- 24896387
TI  - The response of willow grouse chicks to auditory stimuli 2. Synthesized brooding
      calls attract machine-incubated chicks.
AB  - Willow grouse (Lagopus l. lagopus) chicks appear to possess a 'template' of the
      hen's brooding call. Chicks newly hatched from machine-incubated eggs were
      therefore exposed to a number of electronically synthesized approximations to
      brooding calls. These sounds were either paired with a recording of a grouse
      hen's brooding call, or were played alone. Some of the synthesized calls
      (repetitive, low-frequency) attracted chicks, while others appeared to be
      aversive. None of the synthesized calls drew chicks away from the recorded hen
      call. These results suggest that grouse chicks will approach a wide range of
      attraction calls which have certain minimum features. 

PMID- 24896388
TI  - Testosterone-induced precocious sexual behavior in chickens differing in adult
      mating frequency.
AB  - Precocious adult sexual behavior was determined for chicks from two lines of
      chickens selected bidirectionally for adult mating frequency. Three-day-old
      chicks were injected with either 0 or 12.5 mg testosterone cypionate (TC) in
      sesame oil, and their sexual responses to a hand thrust test (HTT) measured at
      10, 12, 14, 16 and 18 days of age. TC stimulated copulation in both the high and
      low mating line, while birds receiving injections of the vehicle only, failed to
      copulate. There were differences in precocious sexual behavior between lines at
      this young age, although further differential maturation of neural tissues
      mediating mating behavior may occur. Courts, mounts, treads and matings were
      determined for these same birds at 7 weeks of age, following treatment with 25 mg
      TC. Differences were found between the lines, with high mating line birds scoring
      higher than low mating line birds for all behaviors measured. Early treatment
      with TC, however, had no direct effect on sexual behaviors at this age.
      Correlations between 7-week behaviors and HTT scores were determined and their
      possible meanings discussed. 

PMID- 24896389
TI  - The ontogeny of crowing and copulatory behavior in Japanese quail (Coturnix
      Coturnix Japonica).
AB  - The onset and development of sexual behavior were examined in the male Japanese
      quail. Sixteen individuals were observed for crowing, tested for mating, and
      measured for cloacal gland area at 2-day intervals from day 10 to day 60
      posthatch. Onset of the behaviors occured in a sequence. Crowing began at 32.8
      days, mating attempts at 34.3 days and mating (cloacal contacts) at 36.9 days.
      Frequencies of each of these behaviors inceased rapidly from the time of onset.
      The order in the onset of sexual behaviors and the subsequent rapid increase in
      frequencies of all behaviors following their onset, indicates that there may be a
      single physiological factor which determines the characteristics of these events.

PMID- 24896390
TI  - Cyclic proceptivity in a captive female orang-utan (Pongo Pygmaeus Abelii).
AB  - An adult male-female pair of orang-utans was observed for a 3-month period,
      commencing with the introduction of the animals to each other. After
      approximately 2 weeks, the female began to show proceptive behaviors towards the
      male. Two other proceptive periods were observed, occuring from 26 to 30 days
      apart, and lasting for 4-6 days. These female-initiated periods of sexual
      activity began with increased locomotor activity, solitary play, proximity to the
      male, following the male, and social grooming. The peak periods of proceptive
      behaviour included hand-genital contact, mouth-genital contact, rolling the male
      onto his back, both dorso-ventral and ventro-ventral mounting, and pelvic
      thrusting. Although hormonal levels could not be assessed in this study, it is
      believed that these peaks coincided with ovulation. In previous reports, the
      presence of proceptive behaviors was perhaps over-shadowed by highly aggressive
      sexual behavior on the part of male orang-utans. The visibility of proceptivity
      in this study is attributed to the large cage which allowed the female to escape
      the male's advances, enabled distance between the animals when they preferred it,
      and continuous exposure of the orangs to each other. This female orang-utan
      behavior was compared to the female sexual behaviours of the other great ape
      species - the chimpanzee and the gorilla. 

PMID- 24896391
TI  - Observations on a newly described usage of the primate play face.
AB  - Previously, the use of the relaxed open-mouth face (play face) in primates has
      been considered to be solely associated with play, both solitary and social. In a
      captive group of long-tailed macaques (Macaca fascicularis) one variant of this
      facial signal (mime open- mouth face) was found to occur in apparently non-play
      social interactions. The nature of these interactions is compared and contrasted
      with social play, revealing that they differ in many respects. A general
      qualitative description of the non-play interactions is provided, including
      prominent behavioral elements involved, age-sex class and relative status of
      participating individuals, and some speculations concerning potential functions. 

PMID- 24896392
TI  - Directions of migrating monarch butterflies (Danaus Plexippus; Danaidae;
      Lepidoptera) in some parts of the eastern United States.
AB  - In September 1977, the directions of 477 migrating monarch butterflies were
      recorded at five locations in the Eastern United States. The monarchs moved
      highly directed generally to the southwest, roughly in accordance with the
      orthodrome direction, to their assumed winter quarter in Mexico. Deviations from
      the precise direction seemed to be due at least partly to wind drift; major drift
      required navigational compensation. 

PMID- 24896393
TI  - Response latency of conditioned avoidance responses during generalization
      experiments in self-stimulated rats.
AB  - Rats exhibiting steady self-stimulation behavior were trained to avoid a
      footshock after presentation of a unique brain rewarding stimulation of the
      postero-lateral part of the hypothalamus. Fifty percent of the animals tested
      were able to learn this conditioning paradigm. An hypothesis based upon modified
      internal physiological state elicited by the hypothalamic stimulation is
      discussed to explain the remaining half of the sample which failed to be
      conditioned. In the conditioned rats it seems that the time-dependent variable,
      the latency of response, can be used as a valid index for other experiments in
      which it is wished to study the internal decision process used to discriminate
      different hypothalamic stimulations in terms of their rewarding value. 

PMID- 24896396
TI  - Biological determinants of sexual behaviour J.B. Hutchison (Editor). John Wiley
      and Sons, Chichester, New York, N.Y., Brisbane, Qld, Toronto, Ont., 1978, 822
      pp., L19.00, ISBM 0-471-99490-1.

PMID- 24896398
TI  - Platform for identification of Salmonella serovar differentiating bacterial
      proteins by top-down mass spectrometry: S. Typhimurium vs S. Heidelberg.
AB  - Intact protein expression profiling has proven to be a powerful tool for
      bacterial subspecies differentiation. To facilitate typing, epidemiology, and
      trace-back of Salmonella contamination in the food supply, a minimum of serovar
      level differentiation is required. Subsequent identification and validation of
      marker proteins is integral to rapid screening development and to determining
      which proteins are subject to environmental pressure. Bacterial sequencing
      efforts have expanded the number of sequenced genomes available for single
      nucleotide polymorphism (SNP) analyses, but annotation is often missing, start
      site errors are not uncommon, and the likelihood of expression is not known. In
      this work we show that the combination of intact protein expression profiles and
      top-down liquid chromatography-mass spectrometry (LC-MS/MS) facilitates the
      identification of proteins that result from expressed serovar specific
      nonsynonymous SNPs. Combinations of these marker proteins can be used in assays
      for rapid differentiation of bacteria. LC-MS generated intact protein expression
      profiles establish which bacterial protein masses differ across samples and can
      be determined without prior knowledge of the sample. Subsequent top-down LC-MS/MS
      is used to identify expressed proteins and their post-translational modifications
      (PTM), identify serovar specific markers, and validate genomic predicted
      orthologues as expressed biomarkers. 

PMID- 24896400
TI  - Effects of experience on agonistic behavior among American goldfinches.
AB  - I investigated the effect of a winning or losing experience on the outcome of an
      individual's next aggressive encounter among captive American Goldfinches
      (Carduelis tristis ). Aggressive encounters occurring over access to a feeder
      were videotaped during the winter of 1985-1986. Both dominants and subordinates
      were more likely to win their next encounter after a win than after a loss.
      Individuals were more likely to initiate their next encounter and use higher risk
      displays after a win than after a loss. 

PMID- 24896399
TI  - Signals for food facilitate gerbils' foraging behaviour.
AB  - To determine if cues signalling the availability of food results in more
      effective foraging, we trained experimental but not control gerbils to associate
      a cue (a wire mesh-or pebble-covered floor) with food availability in a Y-maze.
      Both experimental and control subjects were subsequently tested on an eight arm
      radial maze foraging task. For both groups half of the arms contained food; for
      the experimental group the baited arms contained the cue previously associated
      with food. Trained subjects foraged much more efficiently, a result consistent
      with the notion that animals utilize cues signalling the presence of food to
      guide their foraging behaviour. 

PMID- 24896401
TI  - Positive contrast as a function of component duration using a within-session
      procedure.
AB  - Pigeons pecked keys for food reinforcers delivered by multiple schedules. Three
      experiments examined changes in the size of positive contrast with changes in
      component duration. They used a within-session procedure which measured rates of
      responding during the baseline and contrast phases within the same session.
      Contrast was largest for shorter components, a result similar to that found using
      traditional procedures. Therefore, the present results provide preliminary
      support for the use of the within-session procedure to study contrast. They also
      showed that the inverse relation between key-peck contrast and component duration
      is a robust finding which survives major changes in procedure. Finally, they
      suggest that different functions relate the size of contrast to component
      duration for key pecking and treadle pressing. 

PMID- 24896402
TI  - [Not Available].
AB  - One frequent criticism of the battery cage is that existing cages are too small.
      The present study used operant conditioning techniques to assess to what extent
      adult domestic hens were prepared to "work" (key peck) in order to increase the
      size of their cages. Twenty-seven groups of 4 hens were used. Each group of 4
      birds was housed in a cage which had a minimum surface area of 1600 cm2 and a
      maximum surface area of 6100 cm2. Operant key pecking allowed the birds to
      increase, and maintain, the size of their cage at any value between the minimum
      and the maximum. The results obtained indicated that groups of 4 birds
      preferentially maintain a cage surface area of 2500 cm2 (i.e. 625 cm2/bird).
      Furthermore birds appeared to avoid a cage surface area of 4300 cm2 (i.e. 1075
      cm2/bird). It is suggested that a cage size of 2500 cm2 may be the optimum for
      groups of 4 hens and that, at least in small groups of laying hens, the
      relationship between cage size and welfare is not linear. 

PMID- 24896403
TI  - Early exposures to intermale aggression increases the adult aggression of male
      rats.
AB  - Intact litters of rats were exposed to three brief episodes of intense paternal
      aggression against an unfamiliar adult conspecific prior to weaning on day 31.
      Control litters were not exposed to paternal conflict. Male offspring of both
      groups were given a long-term test of their aggression against an unfamiliar
      intruder when the subjects were 103-114 days old. During the initial 10-minute
      observational phase of the aggression test, few animals in either group attacked
      the intruder, but intruders lost more bodyweight during the 221 2 -hour test when
      placed into the cages with the aggression-exposed subjects. Thus, early exposure
      to aggressive exchanges between adult animals increases the use of an aggressive
      strategy during subsequent confrontations with unfamiliar conspecifics. Two
      mechanisms possibly underlying this phenomenon are discussed. 

PMID- 24896404
TI  - Spiny mouse's (Acomys Cahirinus) use of its distance senses in prey localization.
AB  - This study examined the relative importance that olfaction, audition and vision
      played in the spiny mouse's localization of insect prey. These three senses were
      blocked singly or in various combinations so that a mouse was tested under 8
      different situations with a tethered live cricket and four with a dead cricket.
      The mice did not rely on one particular sense more than the others, but in
      certain situations olfaction and audition proved more important than vision in
      the localization of a live cricket. In the case of a stationary cricket, the mice
      relied more on olfaction than vision. This pattern of use is what would be
      expected of a nonspecialized omnivore and may represent what ought to be found in
      many other rodent species. 

PMID- 24896405
TI  - Individual or paired exposure of domestic chicks to an open field: Some
      behavioural and adrenocortical consequences.
AB  - The interpretation of open-field behaviour in chickens is unclear because
      conflicting effects of manipulating the social environment during testing have
      been reported. The behavioural and adrenocortical responses of chicks exposed
      individually or in pairs to an open field were, therefore, examined in the
      present study. Chicks tested individually showed significantly higher levels of
      activity, vocalization, defaecation and plasma corticosterone but took longer to
      ambulate and preened and pecked at the environment significantly less than their
      paired counterparts. There were no differences between treatment groups in either
      the durations of freezing or the latencies to vocalize. Social motivation is
      thought to be an important variable influencing the chicks' strategy but the
      present findings are wholly consistent with an interpretation of chicks' open
      field responses based on the fear hypothesis. 

PMID- 24896406
TI  - The role of experience in foraging shoals of bluntnose minnows (Pimephales
      Notatus).
AB  - The hypothesis that naive shoal members begin to feed more quickly on a food,
      novel in type, location and required foraging technique, when informed group
      members are present was tested with bluntnose minnows (Pimephales notatus )
      foraging in shoals of various sizes. Naive individuals in mixed shoals (one-third
      of the shoal members experienced with the new food and two-thirds naive) of 3
      fish, decreased their foraging latency as compared to those in shoals of 3 naive
      fish when foraging on a novel food. In mixed shoals consisting of 6, 9 and 12
      individuals, naive fish did not begin foraging more quickly than those in shoals
      of the same size consisting entirely of naive fish. In these larger shoal sizes,
      the naive fish remained together near the bottom instead of following the smaller
      number of informed fish to the surface where the novel food was located. 

PMID- 24896407
TI  - Foraging choice in laboratory rats: Constant vs. variable delay.
AB  - Deprived animals choosing between a variable delay (with mean t ) and a constant
      delay of t s prior to availability of food usually prefer the variable delay.
      Models of discounted future rewards predict such preference. For comparison we
      write a model assuming that a forager minimizes the probability that its total
      food intake falls short of a fixed requirement. This model predicts preference
      for the constant delay at sufficiently high average feeding rates. In a test of
      the models, laboratory rats (Rattus norvegicus ) chose between a constant t s
      delay and a variable option with equiprobable delays of 1 and (2t -1)s. Each
      subject was presented with the same sequence of mean delays. Each delay was
      experienced by the subjects for seven consecutive test days. Between the first
      and the fourth test day, a subject's body weight was decreased from 85 to 75
      percent of free- feeding weight. Between the fourth and the seventh test day, a
      subject's body weight was increased to 85 percent of free-feeding weight. As t
      increased from 5 to 50 s, subjects first preferred the constant delay and then
      came to prefer the variable delay. Thereafter, as t was decreased to 5 s,
      subjects retained preference for the variable delay, but the strength of that
      preference declined at t decreased. Short-term variation in body weight, at a
      given value of t , did not influence preference significantly. Despite the rats'
      initial preference for constant delays, we tentatively conclude that our results
      appear more consistent with the discounting model than with the energy budget
      model. 

PMID- 24896408
TI  - Determination of the hunting strategy in the genus smithistruma (Formicinae -
      Myrmicinae) by the kind of prey.
AB  - When they prepare to capture a collembolan (principal prey), the hunting workers
      from colonies provisioned with collembolans (control) present at the beginning of
      their behaviour sequence a phase of pointing which is acquired progressively,
      (the collembolans are attracted to the workers in the pointing phase, Dejean
      1985a). On the other hand, if during the first weeks of their having become
      hunters, the workers only encounter alternative prey (test), the pointing phase
      is not acquired even if afterwards there is frequent contact with collembolans.
      Instead, the workers approach the prey slowly. After the failure of a first
      capture attempt, the workers present a stereotyped alternate behaviour. If they
      find the prey that escaped, the approach is rapid, and attack is immediate no
      matter what the prey type or the origin of the worker (test or control). The
      overall outcome (first and second try) shows that the controls stay specialized
      in the capture of collembolans while the test workers are generalist predators. 

PMID- 24896412
TI  - Knowledge of session length is a determinant of within-session response patterns
      in a human operant paradigm.
AB  - Two experiments were conducted during which undergraduates responded during a
      variable-interval (VI) 60-second operant task. The first experiment consisted of
      either three 60-minute sessions or three 30-minute sessions. During Experiment 1
      subjects were informed as to the length of the session and the number of sessions
      that would be conducted. During the second experiment subjects were told that
      they would be participating in three 60-minute sessions but they actually
      participated in one 30-minute session. During Experiment 1 the rate of responding
      increased significantly within the sessions for 30-minute sessions but did not
      change significantly for 60-minute sessions. Response rate did not change during
      the 30-minute session in Experiment 2. The results of these experiments
      demonstrate that, under certain circumstances, rate of responding changes within
      sessions for humans. The experiments also provide some evidence that a
      prospective factor influences the rate of responding within an experimental
      session for human subjects. 

PMID- 24896414
TI  - Social-maternal relations in Coelotes terrestris (Araneae, Agelenidae): Influence
      of the female reproductive state on its tolerance towards conspecific
      spiderlings.
AB  - Recent studies have shown that maternal prey-supply activity in Coelestes
      terrestris depends on a specific internal state of the female linked with the
      emergence of its progeny. The present study clarifies the conditions which
      underlie female tolerance towards the young. Females at various stages of the
      reproductive cycle were each confronted with a group of ten 3-week-old spiders
      for 24 hours. Nursing and post-dispersal females perfectly tolerated the young
      presented to them while pre-laying and incubating females, on the contrary, were
      rather hostile and killed a number of the young presented to them. The difference
      in the attitude of the two categories of females shows that tolerance towards the
      young, like the prey-supply activity, depends on its reproductive state. 

PMID- 24896413
TI  - Behavioral differentiation of mice exposed to a water tank social interaction
      test.
AB  - Male or female C57BL/6J mice were exposed to a water tank in which food could be
      obtained only by wading in the water towards a feeder. Behavioral differentiation
      occurred in that three distinct categories could be distinguished: major carriers
      (transporting over 80% of the food pellets), sporadic carriers (transporting less
      than 20% of the food pellets) and non-carriers. In the elevated + -maze, major
      carriers were more willing to explore open spaces than non-carriers. Sporadic
      carriers showed some evidence of the same tendency of decreased anxiety, but in a
      minor way. The willingness of mice to become carriers is associated with their
      willingness to explore novel areas. This test may be useful for the assessment of
      anxiolytic compounds in a social situation. 

PMID- 24896415
TI  - Discrimination and recognition of photographs of places by homing pigeons.
AB  - Operant studies on pigeons using slide-projected images suggest that photographs
      of geographical locations might be used as a research tool to study the
      importance of visual landmarks in homing. Before using this method, however, it
      is necessary to show that pigeons do see photographic slides as representing real
      world locations. After reviewing the evidence for picture-to-object
      correspondence for geographical locations in pigeons, we report the results of an
      experiment designed to test whether outdoor experience at a location affected
      homing pigeons' ability to categorise slides of that versus another location
      displayed in an operant set-up. Four birds visited one location immediately
      before each experimental session; four birds visited an irrelevant location. No
      effect of outdoor experience was found on acquisition, or transfer to novel
      stimuli. The possible reasons for limitations on picture-to-object correspondence
      are discussed. 

PMID- 24896416
TI  - Response strategies during acquisition of serial learning in pigeons (Columba
      livia).
AB  - Pigeons were exposed on fixed duration sessions to four chromatic stimuli and
      trained to perform a 2-item sequence. A detailed analysis of incorrect responses
      performed on each trial prior to completion of the sequence led to distinguish
      three learning stages. Already on initial sessions animals responded
      significantly more frequently to relevant stimuli than to irrelevant ones
      indicating stimulus control by salience. During an intermediary stage, responding
      to item 2 increased significantly and animals started an increasing number of
      trials with item 2, suggesting stimulus control by recency. On the final session
      the correct sequence outnumbered significantly the reverse sequence, suggesting
      control by order, while recency and salience effects were present to a lesser
      extent. Repeated pecks, i.e. consecutive pecks on the same cue, occurred on the
      four cues on the first session and decreased significantly on the last session
      for irrelevant colours. In addition, when key pecks were followed by a brief
      sound signal, repeats on relevant stimuli decreased while efficient colour pecks
      (i.e. when repeats were ignored) on these stimuli increased. These findings are
      discussed in the light of those obtained in traditional chaining paradigms. 

PMID- 24896417
TI  - Chemosignals and activity of wild stock house mice, with a note on the use of
      running wheels to assess activity in rodents.
AB  - Two control tests and an experimental test were used to explore the effects of
      urinary chemosignals on activity in house mice (Mus domesticus). Control tests
      revealed that Using running wheels for measurement periods of up to a week, we
      tested whether any of eight urinary odours or water (control) influenced activity
      in male and female mice that were prepubertal, pubertal, or adult. 

PMID- 24896418
TI  - Within-session changes in responding during variable interval schedules.
AB  - Four rats and four pigeons responded for food delivered by variable interval
      schedules that provided programmed rates of reinforcement ranging from 15 to 480
      reinforcers per hour. Rate of responding increased, decreased, or increased and
      then decreased within sessions. The within-session pattern of responding changed
      with changes in the programmed rate of reinforcement and with the species of
      subject. Finding within-session changes in responding during variable interval
      schedules extends the generality of these changes to another schedule. It implies
      that variable interval schedules should be used cautiously as baselines for
      assessing the effects of other variables, such as drugs. Finally, the results
      suggest that systematic pauses in responding during the session may contribute to
      the decreases in the average rates of responding with increases in the rates of
      reinforcement that are sometimes observed when subjects respond on variable
      interval schedules that deliver high rates of reinforcement. 

PMID- 24896419
TI  - Hippocampal cholineacetyltransferase activity, agonistic behaviour and social
      stress in male rabbits.
AB  - Agonistic behaviour was observed in pairs of unfamiliar male rabbits living in an
      outdoor enclosure. Attack, Chase, Follow and Cross-over were scored. On the basis
      of their frequencies the subjects in the pair were assigned a first or second
      rank-position. Hippocampal cholineacetyltransferase (ChAT) and plasma levels of
      corticosterone were considered in relation to rank. ChAT levels in the dorsal
      hippocampus varied in relation to agonistic behaviour. Second-ranking subjects
      had significantly higher levels of ChAT than the first-ranking animals and had
      levels of corticosterone which were markedly higher at the end of the
      experimental period than at the beginning. A negative correlation was found
      between Attack and ChAT levels in the dorsal hippocampus. These results suggest
      the presence of social stress in the second-ranking animals and indicate a state
      of activation of the hippocampus in relation to agonistic behaviour. 

PMID- 24896420
TI  - Female preference and filial cannibalism in Aidablennius sphynx (Teleostei,
      Blenniidae); a combined field and laboratory study.
AB  - In the fish Aidablennius sphynx, in which males continuously care for up to 7000
      eggs throughout the breeding season, females prefer to mate with males that
      already guard eggs. The present study shows that this preference appears to be
      adaptive because the probability of eggs being cannibalized decreased with brood
      size. In the field, on average 36 eggs disappeared from nests per day, where the
      main egg predator seemed to be the guarding male. Experiments showed that males
      selectively consumed dead eggs, probably to prevent the spread of infections.
      However, only with large broods did the numbers of eggs cannibalized in the field
      correspond to the egg mortality rate, that was determined to be 0.8%. When
      guarding small broods, males have probably also eaten healthy eggs. Breeding
      males suffered an average weight loss of 19.4%. This suggests that breeding males
      are restricted in foraging opportunities. When a male was experimentally fed, he
      cannibalized fewer eggs only when guarding small broods, not when guarding large
      broods. Therefore, it seems that caring males daily harvest eggs to remain in
      sufficient condition. In large broods they use eggs that recently died. When the
      male is guarding small broods the low numbers of dead eggs do not suffice, and
      healthy eggs are also eaten. 

PMID- 24896421
TI  - 'Copying mate choice': Which phenomena deserve this term?

PMID- 24896422
TI  - Habitat richness affects home range size in the red fox Vulpes vulpes.
AB  - The spatial behaviour of the red fox Vulpes vulpes shows a great flexibility
      (Voigt and Macdonald, 1984). Home range size varies from 10 to over 5000 ha
      (Macdonald, 1987; Voigt, 1987). In carnivores, variations in home range size,
      weighed for body mass (Gittleman and Harvey, 1982), are largely related to
      differences in habitat productivity, but the intraspecific local variation in
      home range size can be only partially explained by differences in productivity.
      Macdonald (1981, 1983) suggested that home range size and configuration were
      determined in the red fox by the dispersion of food-rich patches. More recently,
      it has been found that In this paper, evidence for a strong influence of habitat
      richness on home range size of the red fox is reported. 

PMID- 24896423
TI  - Highly sensitive and multispectral responsive phototransistor using tungsten
      doped VO2 nanowires.
AB  - In this work, we report a novel and feasible strategy for the practical
      applications of one-dimensional ultrasensitive phototransistors made of tungsten
      doped VO2 single nanowires. The photoconductive response of the single nanowire
      device was investigated under different visible light excitations (405 nm, 532
      nm, and 660 nm). The phototransistor device exhibited ultrafast photoresponse,
      high responsivity, broad multispectral response, and rapid saturation
      characteristic curves. These promising results help to promote the applications
      of this material in nano-scale optoelectronic devices such as efficient
      multispectral phototransistors and optical switches. 

PMID- 24896424
TI  - Central and peripheral endocrine correlates of the immobility reaction in the
      toad Bufo bufo.
AB  - The immobility reaction, which may be regarded as an innate fear response, has
      been observed in several animal species including Amphibians. Its endocrine
      correlates were established in the newt Triturus cristatus and in the toad Bufo
      bufo, in which the duration of immobility is influenced by sex and mating. The
      aim of the present study was to investigate the possibility of a relation between
      immobility reaction and central hormonal receptors. Testosterone (T) binding
      capacity in the brain and plasma sex steroids were studied in four groups of male
      and female sexually active and inactive toads in which the immobility reaction
      was induced by inversion (A) and by inversion +pressure (B). Females were found
      to be more susceptible than males to immobility A, whereas males were more
      susceptible to B. Sexually active animals with higher plasma levels of sex
      steroids were less susceptible than inactive ones. Lower T binding capacity in
      the brain and higher affinity is associated with sexual activity. Susceptibility
      to the immobility was negatively correlated with plasma sex steroids and
      positively correlated with T binding capacity. A reciprocal effect was found to
      exist between endocrine parameters at central and peripheral level, both
      controlling immobility behaviour. Mating may influence susceptibility to
      immobility through an endocrine mechanism. 

PMID- 24896425
TI  - The effects of associative congruence and dimensional similarity of samples in
      delayed matching by pigeons.
AB  - Pigeons were trained with a many-to-one mapping of sample stimuli onto comparison
      stimuli. The red comparison stimulus was correct after red, vertical line or
      circle sample stimuli, and the green comparison was correct after green,
      horizontal line or triangle sample stimuli. On control trials, only a single
      sample stimulus was presented. On congruent trials, two sample stimuli were
      presented and both were associated with the same comparison response. On
      incongruent trials, two sample stimuli were presented and they were associated
      with different comparison responses. The two sample stimuli on congruent and
      incongruent trials were either from the same stimulus dimension or from different
      stimulus dimensions. Matching accuracy on congruent trials was equivalent to that
      on control trials regardless of whether the two samples were from the same or
      from different stimulus dimensions. Matching accuracy on incongruent trials was
      significantly lower than on control trials. In addition, accuracy was equivalent
      when the incongruent samples were from the same dimension and when they were
      different dimensions. These findings were robust across various interstimulus
      intervals and retention intervals in three experiments. The results indicated
      that pigeons, unlike monkeys, are insensitive to the dimensional similarity of
      sample stimuli. The data suggest that pigeons do not retrospectively code samples
      in a many-to-one procedure, rather they are consistent with the notion that
      associating more than one sample with the same comparison produces a common,
      shared memory code for the various samples. This common code could be an
      intermediate sample code ("Sample A", "Sample B"), or a prospective response code
      ("Peck Red", "Peck Green"). 

PMID- 24896426
TI  - Age decisions on familiar and unfamiliar faces.
AB  - The extraction of age is among the "early visual processes" that operate on
      faces. Current cognitive models mention this operation, but data on the subject
      is rare. In the first experiment, a series of familiar and unfamiliar faces were
      displayed to subjects who were asked to make old/young categorizations. To test
      how early this operation occurs, the same material was used for familiarity
      decision. Finally, the stimuli were displayed centrally to 16 subjects and
      laterally to 32 subjects. The age decision was easier and quicker than the
      familiarity decision; the familiarity decision was unaffected by the age of the
      faces, while face familiarity affected the extraction of age. In a second
      experiment (40 subjects), we manipulated the ambiguity of the apparent age and
      conditional tasks were used, i.e., the subjects had to process both age and
      familiarity in a single task. The results suggest that age extraction is an
      operation that is mandatory for an efficient recognition process. Therefore, it
      is proposed to dissociate, within the semantic visually derived codes, the
      processing of age from the processing of sex and race. 

PMID- 24896427
TI  - Is fear present following sustained asymptotic avoidance responding?
AB  - The present experiment provided a direct test between a "fear" and an
      "expectancy" interpretation of avoidance in extinction. The test was suggested by
      Seligman and Johnston (1973). Three groups of rats were given discrete-trial
      avoidance training in a modified shuttlebox apparatus until they reached a
      criterion of either 5, 25, or 50 consecutive avoidance responses with a latency
      of less than four seconds (the duration of the CS). Asymptotic responding was
      reached quickly and continued to be maintained until avoidance training was
      discontinued. A transfer test using a lick suppression paradigm followed
      avoidance training. Seligman and Jonhston predicted that following asymptotic
      performance, fear (as indexed by lick suppression) would extinguish quickly and
      not be present during sustained avoidance responding. On the other hand, fear
      theory argued that "fear" needed to be present for avoidance responding to occur.
      The data clearly supported fear theory. All groups displayed good suppression to
      the CS, including the group which experienced 50 consecutive short-latency
      avoidance responses. Additional implications of the data were discussed. 

PMID- 24896428
TI  - Male-female interactions in staggerer and non-mutant mice: impairment to react to
      novelty as a possible explanation of staggerer male social behaviour.
AB  - Associated with neurological anomalies, many behavioural deficits are induced by
      the staggerer mutation. In order to define the consequences of this mutation on
      the staggerer male social behaviour we realised experimental dyadic encounters
      with non-mutant and unfamiliar females, either in estrous or in anestrous
      condition. We compared mutant behaviour to non-mutant male behaviour. Staggerer
      male behaviour presents the same characteristics during encounters with both
      types of females. It differs from non-mutant male behaviour in a similar context.
      Non-mutant males present more interactions (social interest, sniffing and sexual
      behaviours) with females than staggerer males. Females modify their behaviour as
      a function of their state of receptivity and according to their partner.
      Behaviours of staggerer males towards females may be interpreted in terms of
      general exploratory behaviour. 

PMID- 24896429
TI  - Multi-choice food preference behaviour of the Indian mole rat Bandicota
      bengalensis.
AB  - Multi-choice food preference behaviour of the Indian mole rat Bandicota
      bengalensis has been studied with 4 and 8 foods consisting of cereals and a pulse
      in rat pens which had floor area of 143 x 94 cm and 143 x 94 plus 220 x 82 cm,
      respectively, and separate food and nest boxes. Nine combinations of three
      texture forms of 4 foods and one combination of 8 foods were tested. Significant
      differences were observed in the daily consumption of different foods
      irrespective of the daily clock-wise rotation in the location of the foods. The
      number of available foods, their taste and textural qualities were found to
      influence the feeding responses of B. bengalensis. In multi-choice feeding tests
      with 4 foods, small sized and less harder grains as of rice and millet were eaten
      more than those of maize and gram, while the maize flour was more preferred than
      the flour forms of other grains. Compared to other foods in any combination, rice
      in its whole (W), cracked (C) and flour (F) forms was generally eaten more than
      the W and C forms of maize and gram and F form of gram and millet. However, the 8
      foods were eaten in the following order of preference: millet (W) > millet (C) >
      jowar (C) > wheat (C) > rice parmal (C) > rice basmati (C) > gram (C) > maize
      (C). The mole rat appeared to establish a particular order of preference of foods
      on the first day of feeding, and that was maintained on subsequent days by daily
      exploration and sampling of all foods. The particular patterns of food
      preference, as established in combinations of 4 foods and 8 foods, were not
      influenced significantly by the changes in location of foods among similar and
      familiar feeding sites of the rats. 

PMID- 24896430
TI  - Oiling behaviour and the effect of lipids on dustbathing behaviour in laying hens
      Gallus gallus domesticus.
AB  - Laying hens oiled the plumage twice a day, while oiling behaviour consisted of a
      bout of five oilings (median value). During one oiling, a hen collected lipids
      from the preen gland with her bill and subsequently performed (as a median) five
      strokes or rubs over and through the feathers. The breast was oiled most, whereas
      during later oilings within an oiling bout the wings and the flanks were oiled as
      well. The back and the tail were seldom oiled. An artificial distribution of
      stale uropygial gland lipids in a more or less natural way on the breast feathers
      within a 3-day period of sand deprivation resulted in an increase of the duration
      of the first dustbath after the deprivation by 12%, compared with a control
      treatment. Within the dustbath, the total number of the side-lying and side
      rubbing elements - two related consummatory dustbathing elements - doubled and
      tripled, respectively. In contrast to these highly significant effects, the
      duration of the dustbathing did not change after a fresh uropygial gland lipid
      treatment, while the effects on side-rubbing and side-lying were not
      straightforward; the total number of the side-rubbing element was doubled, but
      the duration of side-lying was reduced by 29%. The results are discussed in
      relation to the chosen methodology and the maintenance of the lipid condition of
      the integument. 

PMID- 24896431
TI  - Characterizing parameters of response to light intensity for six species of
      frogs.
AB  - A comparative study was made to characterize differences in intensity response by
      six anuran species: Hyla cinerea, Hyla gratiosa, Rana catesbeiana, Rana
      sylvatica, Kassina senegalensis, and Leptodactylus pentadactylus. Considering the
      sigmoid Intensity/Response curve to represent a cumulative Gaussian distribution
      gave a very good fit to the data, for both dark- and light-adapted animals.
      Characterizing parameters from the regression to transformed data gave good
      distinctions between the species for both adaptational states. 

PMID- 24896432
TI  - Test of magnetic sensitivity in seven species of European birds using a cardiac
      nociceptive conditioning procedure.
AB  - An attempt was made to show magnetic sensitivity in seven species of European
      birds captured during their migration. The test was done on the following
      species: Streptopelia turtur (N=8), Streptopelia decaocto (N=2), Corvus monedula
      (N=6); one individual of the following: Corvus corone c., Turdus philomelos,
      Turdus viscivorus, Anas penelope. Most of the individuals were first subjected to
      conditioning to a light stimulus. They were then subjected to differential
      nociceptive conditioning to 100 presentations of a magnetic stimulus (CS+)
      reversing the vertical Z component of the local magnetic field and 100
      presentations of a control stimulus for artifacts (CS-). The two stimuli were
      randomly interdigited. Cardiac activity was used as an index of reactivity
      throughout the study. Results indicate that the magnetic stimuli were not used by
      the birds as a cue presaging the forthcoming shock. We discuss the validity of
      the stimuli and paradigms used to demonstrate magnetic sensitivity in birds.
      These negative findings are related to possible artifactual effects explaining
      suggestive results in homing and zugunruhe experiments, and to local processing
      of magnetic effects without access to higher processes such as learning and
      arousal regulations. 

PMID- 24896433
TI  - Effects of exogenous hormones on the reproductive behavior of adult male domestic
      ducks I. Behavioural effects of intramuscular injections.
AB  - This paper reports the behavioural effects of repeated injections in adult male
      domestic ducks of pregrant mare serum (PMS), human chorionic gonadotropin (HCG),
      testosterone propionate (TP), oestradiol monobenzoate (OB) and progesterone (P).
      The most salient feature of the results was that both gonadotropic hormones had
      very few effects on behaviour. In particular they did not stimulate the social
      displays which were, on the contrary, inhibited to some extent by the three
      steroids including TP. Sexual behaviour was stimulated to a moderate extent by TP
      and by OB injections (except for copulation which was unaffected by the latter
      treatment). These results are discussed in the light of comparable studies in
      mammals and in relationship to the sequence of behavioural and endocrinological
      events observed throughout a reproductive cycle of untreated animals. 

PMID- 24896434
TI  - Effects of exogenous hormones on the reproductive behaviour of adult male
      domestic ducks II. Correlation with morphology and hormone plasma levels.
AB  - The behavioural effects observed following repeated injections of pregnant mare
      serum (PMS), human chorionic gonadotropin (HCG), testosterone propionate (TP),
      oestradiol benzoate (OB) or progesterone (P) were accompanied by significant
      effects on reproductive morphology and on plasma levels of pituitary-gonadal
      hormones. The testes weight was decreased by TP and P treatment, FSH secretion
      was inhibited by the three steroid preparations (TB, OB, P) but LH was not
      suppressed following OB injections (only TP and P were effective in this
      respect). The behavioural effects previously described are discussed in the light
      of the present results and a possible unitary mechanism is proposed for the
      inhibition of social display by TP, OB and P. Correlations between individual
      variations of hormone levels and of behaviour are presented: these are shown to
      be significant in only a few cases. Finally, a tentative model is proposed to
      explain the endocrine basis of the annual reproductive cycle of male ducks. 

PMID- 24896435
TI  - Repeated exposure of the domestic chick to a novel environment: Effects on
      behavioural responses.
AB  - Seven-day-old male and female chicks of three strains were placed individually in
      an open field or novel environment for 15-min periods; this procedure was
      repeated daily for four consecutive days. Several behavioural characteristics
      were recorded and the magnitude and direction of any changes in the
      characteristics with repeated exposure were analysed. Significant decreases over
      time were observed in the following characteristics: latency to the first step,
      duration of freezing, sitting time, lying time, eye-closure and head-shaking,
      whereas significant increases with repeated testing were recorded for distress
      calling, number of steps taken, walking time, pecking, preening and jumping. No
      significant changes were observed in defaecation, standing time, bill opening or
      scratching the litter. The results are discussed in terms of the measurement of
      fearful behaviour under the assumption that experience in a novel environment may
      act to reduce the level of fear associated with that situation. 

PMID- 24896436
TI  - Amnesic effects of electroshock and anoxia on conditioned taste aversion learning
      in rats.
AB  - Albino Wistar rats of both sexes were given a conditioned taste aversion training
      (CTA). Saccharin was used as the conditional stimulus (CS) and apomorphine
      induced illness as the unconditional stimulus (US) on day 4. Amnestic treatment
      with electroconvulsive shock (ECS) or nitrogen anoxia were given to the rats at
      various points within the 180-min long CS-US interval as well as after the US.
      They were reexposed to the CS on days 5 and 6 in order to evaluate CTA and its
      extinction respectively. Apomorphine injection alone produced significant CTA as
      long as the CS-US interval was less than 120 min but not beyond it. Saline
      injections, with or without amnestic treatments, produced only an adaptation to
      and preference for saccharin. ECS could prevent CTA when delivered within 85 min
      before or 110 min after the US. Anoxia was effective at a much shorter range of
      time than ECS. The results are discussed in the perspectives of neophobia,
      saccharin aversion, amnestic agents and the character as well as gradients of
      amnesia produced. 

PMID- 24896437
TI  - The quantitative effect of visual and tactile stimuli on the prey-catching
      behaviour of ferrets (Putorius furo L.).
AB  - The influence of visual and tactile stimuli on the elicitation of prey-catching
      behaviour of ferrets was to be studied. For this study 16 animals, males and
      females, some naive and others experienced in catching and killing mice and rats
      were used. The behaviour of the ferrets toward 16 dummies with different
      characteristics was analysed under standardized conditions. Prey catching
      reactions of ferrets can be elicited by moving dummies. Dummies up to a certain
      size reliably elicit hunting reactions if they are moving at a speed of 25 cm/sec
      to 45 cm/sec. Moving objects, more than double the size of a ferret, cause
      avoiding reactions. Objects with a fur-like surface release more biting than
      objects with a hard surface. When hunting, ferrets-innately-tend to aim at the
      most anterior part of the "prey" and to bite into it, independent of whether
      there is a head-like structure with a neck or not. 

PMID- 24896439
TI  - The ethology of predation E. Curio. Zoophysiology and Ecology, Vol. 7. Springer
      Verlag, Berlin, Heidelberg, New York, 1976, x + 250 pp., DM 72.00 $ U.S. 29.60.

PMID- 24896442
TI  - Innate attraction supplants experience during host plant selection in an obligate
      plant-ant.
AB  - In order to assess the relative contributions of innate attraction and
      environmentally-induced preference to nest plant selection by the obligate plant
      ant Tetraponera aethiops, we submitted both mature and callow workers to paired
      choice tests using the leaves of four plant species, including their natural host
      plant Barteria fistulosa. Mature workers taken from nature as well as mature
      workers after 25 days of laboratory breeding (with or without contact with B.
      fifstulosa leaves) always showed a great preference for shelters made with the
      leaves of B. fistulosa. Similar results were obtained with callow workers
      isolated from any plant material during the first 25 days of imaginal (=adult)
      life or during pre-imaginal development. But those reared in contact with test
      plant leaves for the same two periods showed significantly less preference for B.
      fistulosa than did the controls. As a result, experience gained during the larval
      and nymphal stages as well as during the first part of adult life (i.e. pre
      imaginal as well as early learning) was demonstrated in T. aethiops, but in this
      situation of species-specific interaction it reinforces innate attraction as both
      larvae and adults live in contact with B. fistulosa in nature. These results are
      discussed in comparison with previous data collected on arboreal ants not
      specifically paired with a plant, for which an environmentally-induced preference
      can supplant innate attraction. 

PMID- 24896443
TI  - The proximate and the ultimate: past, present, and future.
AB  - The distinctions inherent in the proximate-ultimate dichotomy have a long
      history. I examined several issues related to this distinction. It is important
      that distinctions among different problem areas be made so that the type of
      answer presented in research in animal behavior is appropriate for the type of
      questions being asked. This may require more than the two-way distinction between
      the proximate and the ultimate. I suggest that such terms as 'function',
      'ultimate', and 'ultimate causation' be re-evaluated. Methodological problems
      encountered when measuring differential adaptive consequences of alternative
      behavioral patterns and when using proximate stimulus control to infer adaptive
      significance require further consideration. 

PMID- 24896444
TI  - Poor rearing conditions and social stress in pigs: repeated social challenge and
      the effect on behavioural and physiological responses to stressors.
AB  - Effects of rearing condition on behavioural and physiological reaction to social
      confrontations and to social and non-social stressors were studied in female
      pigs. The pigs were reared under either poor (the standard farrowing crate) or
      enriched (group of free-ranging sows with piglets) conditions. At the age of 14
      17 weeks, the pigs were exposed to a series of social confrontations where an
      intruder was introduced into the home pen of a resident. The results show the
      presence of a clear difference in terms of aggressive behaviour between residents
      and intruders from enriched but not from poor rearing conditions. Furthermore
      pigs reared under poor conditions inflicted more wounds on each other. We suggest
      that this reflects a difficulty in establishing a dominance relationship in
      poorly reared pigs, caused by impaired development of social skills in these
      pigs. Subsequently, reaction to novel object, non-social and social stress was
      measured in adult age, showing that the effects of rearing conditions are long
      lasting, and give rise to differences in reaction to challenges in that pigs from
      enriched rearing conditions showed more avoidance behaviour than pigs from poor
      rearing conditions. 

PMID- 24896445
TI  - Homeward orientation of pigeons confined in a circular arena.
AB  - To investigate the ability of homing pigeons to determine the home direction at
      the release site before take off, we recorded the oriented movement of 17 birds
      at the point at which they left a circular arena. We subsequently observed the
      pigeons' vanishing bearings. The comparison between the orientation of each bird
      while leaving the arena and at its vanishing point showed that pigeons are
      generally able to orient in a direction close to the home direction before taking
      off. This finding illustrates the possibility of studying pigeon orientation in a
      controllable space with evident advantages for experimentation. 

PMID- 24896446
TI  - Within-session responding when different reinforcers are delivered in each half
      of the session.
AB  - The present study investigated whether within-session responding was specific to
      the reinforcer currently being delivered and whether it was determined solely by
      retrospective factors. In four separate experiments, four rats pressed a lever on
      a multiple variable interval 60-s variable interval 60-s schedule during 60-min
      sessions. A different reinforcer (5% liquid sucrose or food pellets) was
      delivered in each half of the session. Rate of reinforcement in one half of the
      session varied across conditions. Response patterns in the second half of the
      session were unaffected by changes in the conditions of reinforcement of the
      other reinforcer in the first half of the session (specificity). Rate of
      responding was affected, however. The upcoming reinforcer influenced responding
      when sucrose was delivered in the first half of the session and food pellets were
      delivered in the second half, but not when their order was reversed. This effect
      makes contact with several other areas of research (e.g. behavioral contrast).
      They also suggest that the leading explanations for within-session changes in
      responding may be limited or incomplete. 

PMID- 24896447
TI  - Aggressive behaviour of an epigean population of Astyanax mexicanus (Characidae,
      Pisces) and some observations of three subterranean populations.
AB  - The different populations have been tested for aggressive behaviour in groups of
      four to eight animals of both sexes in tanks ranging from 251 to 9501. In
      darkness less aggressive behaviour has been observed with the help of an infrared
      video-camera in the epigean fish and the eyed Micos cave fish. The strongest
      degree of reduction in aggressive behaviour is shown by the totally blind
      populations. The aggressiveness increases in the epigean fish as soon as space
      and food supply diminish. 

PMID- 24896448
TI  - Sensitivity to reinforcement in successive and delayed discriminations.
AB  - Pigeons' responses were recorded in successive 15-s subintervals of 60-s
      components of several multiple variable-interval schedules of food reinforcement.
      In the standard multiple schedule or successive discrimination, discriminative
      stimuli were present throughout each component. In the delayed discrimination or
      memory procedure, red or green stimuli were present in the first 15 s of
      components and were followed by a white stimulus for the remainder of both
      components. Ratios of responses in the first 15 s of the two components, where
      discriminative stimuli were present, were sensitive to ratios of reinforcers
      obtained in the two components, to the same extent in both multiple and memory
      procedures. In both procedures, sensitivity to reinforcement decreased
      systematically over component subintervals, but to a greater extent in the memory
      procedure where discriminative stimuli were absent. The reduction in sensitivity
      with time since presentation of prior discriminative stimuli in the memory
      procedure was therefore influenced by two main factors: delayed stimulus control
      by the discriminative stimuli presented earlier in the component, and a decrease
      in sensitivity to reinforcement with increasing time since component alternation.

PMID- 24896450
TI  - Naloxone influences ultrasonic calling in young mice.
AB  - The ultrasonic calls produced by three day old mice when separated from the nest
      mother and siblings increase in number when naloxone is injected. 

PMID- 24896449
TI  - Keypeck conditioning with reinforcements in two different locations in thrush,
      tit and sparrow species.
AB  - Twenty-one individuals each of the species great tits (Parus major), blue tits
      (Parus caeruleus), marsh tits (Parus palustris), blackbirds (Turdus merula),
      songthrushes (Turdus philomelos), tree sparrows (Passer montanus) and house
      sparrows (Passer domesticus) were conditioned to a keypeck response by means of
      food reinforcement. The site where the reward was given was then changed. The
      number of reinforcements were then counted until the keypeck response followed
      immediately (within 10 seconds) on three successive occasions, and a comparison
      was made between species. Of the species studied the blackbird needed
      significantly fewer instances of reinforcement in order to re-establish an
      immediate keypeck response. A significant difference was also seen between the
      performance of the great tit and marsh tit, as well as between the blue tit and
      the marsh tit. No significant difference was found between the performance of the
      house sparrow and the tree sparrow. 

PMID- 24896451
TI  - Differences in the capacity of male odours to affect investigatory behaviour and
      different urinary marking patterns in two strains of mice, selectively bred for
      high and low aggressiveness.
AB  - The investigatory behaviour of male and female mice on sawdust soiled by male
      mice with different levels of aggressiveness was studied in two experiments. To
      investigate whether high and low aggressive males show different urinary marking
      patterns, a third experiment was set up. The strains TA(Turku Aggressive) and TNA
      (Turku Nonaggressive) have been developed by selective breeding. The TA-soiled
      bedding discouraged investigation by male mice, while females avoided TNA-soiled
      areas. Also the urine marking patterns differed between the high aggressive TA
      and low aggressive TNA males. The results indicate that the urine marking
      behaviour and the odour communication system in the TA and TNA males correlate
      with their hereditarily determined disposition for aggressive behaviour. 

PMID- 24896452
TI  - Choice in humans: Functional properties of reinforcers established by
      instruction.
AB  - Adult human subjects chose between schedules containing stimuli (indicator
      lights) that the subjects were instructed to consider pleasurable. The schedules
      differed in amount of reinforcement (period of illumination) or delay (interval
      between a choice response and light onset). Although subjects preferred large to
      small amounts of reinforcement, they were essentially indifferent between
      immediate and delayed reinforcement. In contrast, previous data on video game
      reinforcement demonstrated preferences for both immediate and large amounts of
      reinforcement. The instructed reinforcer was thus partially effective in
      controlling choice but was not equivalent to a reinforcer that presumably had
      intrinsic value. 

PMID- 24896453
TI  - [Not Available].
AB  - Calls of Ctenodactylus gundi living in semi-natural conditions in our laboratory
      were recorded during various interactions : sexual, agonistic, maternal. The
      physical characteristics of the sounds lead us to describe five major structural
      groups and eleven vocal types. Two of them were recorded only in young animals.
      Intermediate calls and some complex sequences formed by association of two vocal
      types were observed. When emitting sounds, adult gundis can produce eight vocal
      sequences. In two of these phrases a constant association of two different calls
      can be shown. Seven sequences can be related to one of three kinds of social
      interactions : sexual intercourse, withdrawal or aggressivity. In each,vocal
      types are arranged in a gradual order based on the intensity of the interaction.
      The alarm call and two calls produced by young gundis when interacting with their
      mother must be added to the seven sequences described above. Gundi's calls appear
      then to be related both to the quality of social interactions and to the degree
      of arousal of the emitter. Functional problems are discussed and compared with
      available data from some other Rodents. 

PMID- 24896454
TI  - A comparative analysis of feeding and hoarding in hamsters and gerbils.
AB  - Male and female hamsters and gerbils were randomly assigned to one of three
      groups. The animals were tested under ad lib feeding conditions or food deprived
      until they had lost either 10% or 20% of their predeprivation body weight. They
      were given a 30-min. hoarding test for three consecutive days. The results
      indicated that although food-deprived gerbils ate more than control gerbils,
      deprivation had no significant effect on the food intake of hamsters. A sex
      difference was also evident in the food intake of gerbils; males ate more than
      did females. Although there was a sex and species difference in the amount of
      hoarding, deprivation had no significant effect on the amount of hoarding. The
      implications of these results for of different models of hoarding are discussed.
      These models contrast hoarding as a defensive response in the regulation of body
      weight or as an anticipatory activity that is influenced by other selection
      pressures. 

PMID- 24896455
TI  - The effect of intertrial interval food presentions on pigeons' delayed matching
      to sample accuracy.
AB  - Parallel effects of temporal variables on autoshaping and on delayed matching to
      sample performance suggest that delayed matching, like autoshaping, might depend
      upon the within-trial expectancy of reinforcement relative to the overall
      expectancy of reinforcement in the session. This possibility was assessed by
      presenting free food at different times during a 30-sec intertrial interval (ITI)
      in a delayed matching to sample procedure with pigeons. In three conditions a
      single free food presentation occurred, either early, mid-way, or late in each
      ITI; in another condition, three food presentations occurred during each ITI, one
      at each time location. Relative to a baseline condition, in which free food never
      occurred during the ITI, only food presentations late in the ITI produced a
      significant disruption in accuracy, and this effect occurred only at the longest
      of three delays tested. Three free food presentations in each ITI disrupted
      accuracy only to the same degree as a single, late, ITI food presentation. Thus,
      accuracy was affected by the temporal location rather than the frequency of ITI
      food presentations. These effects appear to differ from those of ITI food
      presentations on autoshaping and do not seem to be understandable in terms of
      changes in the background expectancy of reinforcement. It was suggested instead
      that food presented late in the ITI might disrupt subsequent memory processes. 

PMID- 24896456
TI  - Hypothalamic levels of LHRF in male mice of differing social status and from
      individual housing.
AB  - Swiss male mice were individually-housed or maintained in groups of 8 from
      weaning until 80 days of age. At this time, the grouped mice were allocated to
      new groups of 5-6 previously unfamiliar individuals. Identified dominants were
      then caged with two clearly submissive males for 1 week. At this time
      hypothalamic samples were taken from the dominant and one subordinate and from a
      number of long-term individually-housed males. A radio- immunoassay for LHRF was
      carried out. The levels of this hypothalamic releasing factor were significantly
      higher in both dominant and subordinate grouped mice than in 'isolates'. Mice of
      differing social status showed comparable titres of this hormone. The results
      suggest that social conflict and/or disturbance augments this factor in mice
      irrespective of the social status achieved by individual animals. 

PMID- 24896457
TI  - Breeding history and olfactory discrimination in the Syrian hamster.
AB  - The ability of outbred female Syrian hamsters to differentially respond to urine
      samples obtained from either inbred or outbred Syrian males was examined. The
      odors obtained from the males were introduced into a Y-maze olfactometer. On the
      basis of time spent in proximity to the stimuli, estrous females evidenced a
      preference for the urine of the outbred males. The same females when diestrus
      exhibited no apparent preferences. It is possible that the ability of females to
      make such subtle discriminations may impact on mate selection leading to positive
      assortment. 

PMID- 24896463
TI  - Releaser-induced recognition learning by gastropod molluscs.
AB  - The releaser-induced recognition learning model (Suboski, 1990) is briefly
      introduced and examined in the context of a review of the extensive literature on
      learning by gastropod molluscs. Substantial involvement of learning processes
      were found to occur in the acquisition of food and environmental hazard
      recognition. These findings are consistent with a learning model in which
      releasing stimuli activate a stimulus-substitution mechanism that induces
      recognition of otherwise biologically inert stimuli. According to this model,
      simple recognition learning by molluscs basically consists of the stimulus
      redirection of innately-organized released responses. A releasing stimulus
      activates transfer of control over release of responses from the releasing
      stimulus to an initially-neutral stimulus, typically a temporal predictor of the
      releasing stimulus. The model offers a simple, parsimonious, and comprehensive
      account of molluscan learning that integrates Pavlovian and at least simple
      instrumental conditioning as well as providing a potential explanatory mechanism
      if intriguing indicators of social communication of food recognition by
      gastropods were to be substantiated. 

PMID- 24896464
TI  - Pigeon performance on a variable-interval omission schedule at different levels
      of food deprivation.
AB  - After modifying a variable-interval schedule to include an omission contingency,
      we investigated rates of responding and performance at different levels of food
      deprivation in pigeons. The variable-interval schedule had intervals which
      averaged 30 s in duration. Any response made during a particular interval
      cancelled the food delivery at the end of the interval. Following intervals in
      which no response occured, the first response produced a 6-s access to grain.
      Sessions lasted until 150 of these intervals had been presented. Food deprivation
      was manipulated in two ways. In the first, pigeons started at 90% of their free
      feeding weights and were gradually reduced to their 70% levels. In the second,
      pigeons were maintained at three specific levels of their free-feeding weights:
      70, 80, and 90%. During all sessions, rates of responding and the percentage of
      reinforcers omitted were recorded. The results from both methods of deprivation
      were similar: (1) rates of responding systematically increased as pigeon's body
      weights decreased; and (2) performance, as indicated by the percentage of
      reinforcer omissions, worsened as pigeon's body weights declined. 

PMID- 24896465
TI  - Maternal aggression and inter-individual distance in the broody hen (Gallus
      gallus).
AB  - The broody hen behaves in an aggressive way towards other hens. Pairs of either
      two broody hens, or two non-broody hens, or one broody and one non-broody hen,
      were observed in a small enclosure. Pecking of pen mates was found in pairs of
      broody hens while no pecking was found in pairs of non-broody hens. In pairs of
      one broody and one non-broody hen only the broody hen did aggressive pecking.
      Pairs of broody hens keep at a greater distance from each other than pairs of non
      broody hens. It is suggested that these behaviours function to maintain the brood
      as a discrete unit and facilitate the development and maintenance of the hen
      chick relationship. 

PMID- 24896466
TI  - Nestmate-brood recognition among workers of different social status in Ectatomma
      tuberculatum Olivier (Formicidae, Ponerinae).
AB  - Experiments were carried out to test nestmate-brood recognition in the
      neotropical ant species Ectatomma tuberculatum, belonging to the primitive
      subfamily Ponerinae. In the same laboratory colonies, two behavioural subcastes,
      nurses and foragers, were given simultaneous choices between nestmate and non
      nestmate brood (larvae or cocoons). Nurses and foragers dramatically differed in
      their response during the choice test. Qualitative differences appeared in the
      type of brood tending displayed by the two worker categories. In particular,
      licking and transport were more represented in the nurse than in the forager
      repertoire. Moreover, the number of acts delivered by nurses was significantly
      higher toward nestmate than non-nestmate brood and there was no significant
      difference in the amount of behavioural acts directed by foragers toward the two
      brood categories. The social status of the worker therefore appears to strongly
      influence brood discrimination. 

PMID- 24896467
TI  - Further experimental analysis of the social learning and transmission of foraging
      information amongst Norway rats.
AB  - Adult male Norway rats were tested to see if their foraging efficiency could be
      improved by social learning and to investigate whether foraging information could
      be socially transmitted along a chain of animals. In Experiment 1, 'observers'
      were placed in one of four conditions, distinguished by the nature of their
      experience during an observation phase, in which they either observed: (1) a
      trained conspecific unearthing buried carrot; (2) a trained conspecific digging;
      (3) carrot pieces only; or (4) an empty enclosure (the control group). When
      tested 24 h later it was found that subjects in group 1 alone exhibited a
      significantly elevated foraging ability relative to the control group, being more
      active, and unearthing more carrot pieces in total. The results show that
      perception of a trained demonstrator conspecific successfully foraging for food
      is necessary for social learning of foraging information to occur, probably by a
      local enhancement mechanism. In Experiment 2, chains of transmission were
      established by allowing each observer to act 24 h later as the demonstrator for
      the next observer. In one of two transmission groups subjects were given an extra
      period of individual foraging experience in the test enclosure, with no
      demonstrator present. Enhanced levels of foraging efficiency were maintained
      across eight transmission episodes for both transmission groups relative to a no
      transmission control. Subjects in the group with the additional experience
      unearthed significantly more buried food than subjects in the other transmission
      group. The experiments extend our standard transmission group was upheld. The
      superior performance of demonstrators in this group, as reflected in their higher
      level of carrot digging, suggests that the extra period of experience did indeed
      enhance their ability to act as effective demonstrators. The elevated performance
      of subjects in this group is attributed to a combination of social and individual
      learning. This finding suggests that the stability of social transmission may,
      under some circumstances, be bolstered by individual reinforcement of socially
      learned and enhanced patterns of behaviour. It also lends support to the
      hypothesis, proposed to account for the findings of our earlier study, that
      motivational factors such as fatigue, may detract from subjects' performance as
      demonstrators when this demonstration follows closely after the additional period
      of individual experience, but that a 24 h period is sufficient to allow such
      motivational factors to decay. If individual experience can buttress socially
      learned traits then this interaction may act so as to prolong the period of time
      that a socially transmitted trait remains in a population. It is conceivable that
      an additional period of foraging longer than 10 min may further enhance subjects'
      subsequent performance as demonstrators. The complex relationship between
      individual and social learning has received little attention. It is not clear
      how, if at all, social learning is different from other forms of learning
      (Plotkin, 1988), apart from the obvious requirement that another animal somehow
      be involved in the social learning process. Boyd and Richerson (1985) argue that
      social and individual learning are, at least in humans, alternative ways of
      acquiring a particular behavioural variant. Most recent studies of animal social
      learning, on the other hand, tend to emphasize the stimulus enhancing role of the
      demonstrator animal (Galef, 1988a), thereby suggesting that social learning is a
      sub-category of individual learning. This study shows that individual learning
      can reinforce the acquisition and expression of socially acquired behavioural
      variants. 

PMID- 24896468
TI  - The effect of temporal relationship of stimulus compound on ambiguous
      discrimination in the pigeon's autoshaping.
AB  - Pigeons learned a serial amibiguous discrimination task (FA+, A-, FB-, B+), in
      which the serial presentation of a feature and one target (FA) and the
      presentation of the other target alone (B) were followed by an unconditioned
      stimulus (US), but the serial FB presentation and the presentation of A alone
      were unreinforced. The successful performance of this task supported Holland's
      (1983, 1985) model of the feature modulation asserting that the feature occasion
      sets each target-US association, rather than Rescorla's (1985) model asserting
      that the feature modulates the threshold of the US representation. The result
      that the simultaneous presentation of the feature and the target did not produce
      better discrimination than the serial presentation suggested a 'bidirectional
      occasion-setting' function of the feature. However, the insertion of the temporal
      gap between the feature and the target deteriorated the discrimination, a result
      that disagreed with previous studies of occasion-setting in the rats. Some
      possible reasons of the detrimental effect of the gap were discussed, and a
      unique-cue strategy was suggested as a possible alternative account of the
      discrimination. 

PMID- 24896469
TI  - Hormonal and experiential factors influencing parental behaviour in male rodents:
      An integrative approach.
AB  - Parental Behaviour in rodents has traditionally been modelled on studies of
      maternal behaviour in the female rat. Female parental behaviour is initiated by
      hormonal changes during pregnancy and parturition and by pup stimuli. Models of
      parental behaviour based on the neuroendocrine control of maternal behaviour are
      not appropriate for understanding male parental care. This paper examines seven
      factors which influence the snitiation and maintenance of paternal behaviour in
      male rodents: (1) the mating system of the species; (2) the ecological conditions
      under which the animals live; (3) the male's social experience; (4) sexual
      experience and female stimuli; (5) pup stimuli; (6) hormonal changes in adult
      males in response to female and pop stimuli; and (7) neonatal hormone levels. The
      role of stimuli from the female and pups in activating the neuroendocrine changes
      which may facilitate the onset and maintenance of paternal behaviour is also
      described. The aim of the paper is to provide an integgrative approach to the
      study of male parental care and to stimulate research on the hormonal and
      experiential factors underlying paternal behaviour in male rodents. 

PMID- 24896470
TI  - Competition for associative strength between a punctate signal and contextual
      stimuli: Effect of signal preexposure versus context preexposure.
AB  - Preexposures to a punctate stimulus or to an external context were examined for
      their effect on the competition for associative strength between context and
      stimulus in subsequent aversive classical conditioning. Using rats as subjects
      and freezing as the index of conditioned responding, Experiment 1 showed that
      preexposure to a tone retarded the subsequent acquisition of responding to the
      tone, but enhanced the acquisition of freezing to the conditioning context.
      Experiment 2 examined whether the enhanced contextual freezing in Experiment 1
      was based on the formation of an association between the preexposure context and
      the tone. A tone was preexposed in one context and conditioned in another. A
      subsequent of fear for the preexposure context failed to support the notion of an
      association between context and tone. In Experiment 3, context preexposure was
      given prior to tone conditioning in that context. The acquisition of contextual
      freezing was impaired but the exposure treatment had no augmenting effect on
      freezing to the tone. Collectively, the results suggest that preexposure reduced
      the associability of both the punctate stimulus and contextual stimuli. More
      importantly, the reduced associability of the punctate stimulus resulted in a
      reduced overshadowing of contextual stimuli by the punctate stimulus, whereas the
      reduced associability of the context did not result in a reduced overshadowing of
      the punctate stimulus by the context. 

PMID- 24896471
TI  - Opportunistic adoption of orphaned nests in paper wasps as an alternative
      reproductive strategy.
AB  - Adoption of abandoned or orphaned nests by adult females occurs commonly during
      the colony-founding period of the primitively eusocial paper wasp, Polistes
      dominulus. Our evidence indicates that adoption reflects: (1) 'making the best of
      a bad situation,' for queens who have lost their nests; (2) subordinates leaving
      multiple-foundress associations; and (3) possibly, a 'sit-and-wait' strategy, in
      which non-nesting females wait for nests to be orphaned. A 'it-and-wait strategy'
      implies that wasps facultatively delay personal reproduction rather than that the
      delay in reproduction is due to physiological constraints (sensu Gadagkar,
      1991a). Orphaned nests with related brood are not more attractive than those
      bearing unrelated brood, suggesting that nest-adoption has not evolved primarily
      as a strategy to rescue non-descendant kin. Instead, all wasps tend to adopt
      nests that theoretically maximize their selfish genetic interests: the most
      attractive nests were large combs at an advanced stage of development. These
      nests can produce more workers and are closer to worker emergence, at which time
      colony survival per unit time dramatically rises. The primary proximate cue for
      adoption seems to be whether nests contain later-instar larvae or pupae. Since
      developmental stage of brood correlates with nest size, preferred nests thus tend
      to be relatively mature and large. 

PMID- 24896472
TI  - Maternal investment of communally nursing female house mice (Mus musculus
      domesticus).
AB  - Female house mice (Mus musculus domesticus) belonging to the same polygynous
      breeding unit rear their litters communally. This paper analyzes the consequences
      of communal nursing on the number and weight of offspring produced. The
      reproductive behaviour of monogamous females was compared to that of females
      living in polygynous groups, consisting of either two familiar sisters or of two
      genetically unrelated females (unfamiliar until the age of 7 weeks). The lifetime
      reproductive success of a female was measured as the total number of offspring
      weaned during a lifespan of 6 months (standardized as 120 days after mating at
      the age of 8 weeks). The number of litters produced and average litter size per
      female did not differ significantly between the 3 groups of females. However,
      females communally nursing with a sister weaned significantly more young than a
      monogamously paired female. Those sharing a nest with an unrelated female weaned
      an intermediate number of offspring. Sharing a communal nest with a sister
      significantly increased the total mass of offspring weaned in comparison with
      both monogamous females and unrelated females. Furthermore, communal nests
      improved the birth weight of the young when compared with young in solitary
      nests. By cooperative brood care and communal nursing, females improved the
      weight of the young produced. By having a sister for cooperation, a female futher
      improved the number of offspring weaned when compared with a female rearing
      litters in solitary nests, as well as the combined weight of offspring weaned
      compared with all other females studied. 

PMID- 24896473
TI  - Learning to suckle from an artificial teat within groups of lambs: Influence of a
      knowledgeable partner.
AB  - This work was aimed at finding evidence of observational learning in sheep. The
      task to be learned was that of suckling milk from a bucket provided with teats.
      Lambs were reared in groups of either four neonates and an older lamb accustomed
      to artificial suckling (14 experimental lambs) or five neonates (16 controls).
      One-hour observations were made five times a day. The lambs that learned were
      grouped and observed for three hours once a week. All experimental lambs learned
      within three days as compared to nine for the 16 controls. Experimental lambs
      moved and sniffed or sucked the bucket more often than the controls (2.0 +/- 1.5
      vs. 1.5 +/- 1.0% time spent moving, 7.1 +/- 6.2 vs. 1.6 +/- 1.8 sniffing/hour,
      3.7 +/- 3.6 vs. 1.7 +/- 1.7% time spent sucking, P < 0.05). The time to first
      suckling was not related to these measurements, neither was it related to other
      behavioural traits. Learning to suckle from the teat-bucket may be a socially
      transmitted phenomenon, and not only by enhancement of investigation. 

PMID- 24896474
TI  - Social systems and population cycles in voles. Advances in life sciences. R.H.
      Tamarin, R.S. Ostfeld, S.R. Pugh and G. Bujalska (Eds.). Birkhauser Verlag,
      Basel, 1990, XV +, 229 pp.

PMID- 24896478
TI  - La representation animale By Jacques Gervet, Pierre Livet and Alain Tete. Presses
      Universitaires de Nancy, 212 pp, 1992.

PMID- 24896479
TI  - The behaviour of the horse By Andrew F. Fraser. E.A.B. International, 228 pp.

PMID- 24896481
TI  - Editorial.

PMID- 24896482
TI  - Orientation discrimination and categorization of photographs of natural objects
      by pigeons.
AB  - In Experiment 1, pigeons trained to discriminate rightside-up and upside-down
      orientations of slides of natural scenes with humans successfully transferred to
      new slides of the same kind. Experiment 2 revealed that both the orientations of
      the human figures and of the background scenes controlled the discrimination.
      When they were oppositely oriented, the background orientation cue was dominant.
      In Experiment 3 slides showing objects on a white background were presented
      either rightside up or upside down, with each slide presented in one orientation
      only. One group of pigeons learned to classify the slides according to their
      orientations. The other group learned to classify the slides according to
      arbitrary groupings. When the slides were shown rotated by 180 degrees, the
      latter group continued to discriminate the individual slides (i.e., the pigeons
      showed orientation invariance). The former group classified the rotated slides
      according to their orientations (i.e., orientation discrimination). In Experiment
      4, pigeons learned the orientation discrimination with separate sets of human and
      bird figures. Partial reversal training in one object class transferred to the
      rest of stimuli in this object class but did not to the other object class. These
      results suggest that pigeons can learn to discriminate photographs on the basis
      of orientation but that orientation-based equivalence relationship is not formed
      between object classes. 

PMID- 24896483
TI  - The role of individual differences and patterns of resolution in the formation of
      dominance orders in domestic hen triads.
AB  - This research compares the role of initial individual characteristics to that of
      patterns of resolution in which successive dominance relationships are
      established during the formation of triads in the domestic hen. Combining weight
      and comb size with prior victory or defeat in the site of encounter, we created
      three levels of asymmetries of characteristics for triads of hens. The effects of
      these asymmetries were then examined on the resultant hierarchies and on the
      order of conflict resolution within triads under two different conditions of
      assembly. In one condition (simultaneous triad), the three hens were
      simultaneously introduced to each other and could thus freely choose their
      opponent. In the other condition (step-assembled triad), the hen predicted to
      occupy the highest rank was left on standby and introduced once the other two
      hens had settled dominance. This condition disrupts the normal process of
      hierarchy formation by imposing the first sequence of dominance settlement. We
      found that the structure of triadic hierarchies can be predicted from individual
      characteristics existing prior to hierarchy formation. No difference in the
      resultant structures were found between conditions of introduction, though
      different paths of conflict resolution were followed indicating that individual
      differences had a more determining role on the resultant hierarchies than
      patterns of resolution. In addition to demonstrating that individual differences
      determine resultant triadic structures, the present results also show that the
      same end structures can be reached by following resolution paths that are not
      necessarily of the Double Dominance and Double Subordinance types as prescribed
      by Chase's model. It is also found that in the simultaneous condition hens select
      each other to form pairs. Therefore, individuals do not meet at random but choose
      each other as opponents. The two hens predicted from individual differences to
      occupy the highest ranks first settle dominance, followed by settlement between
      the winner of the previous encounter and the bystander. 

PMID- 24896484
TI  - Coherent use of information by hens observing their former dominant defeating or
      being defeated by a stranger.
AB  - This study examines the role of observation during the formation of triads in
      female domestic hens. Results indicate that during hierarchy formation, a hen
      observing agonistic interactions and conflict settlement between its former
      dominant and a stranger uses this information when in turn confronted by the
      latter. Under a first condition (E, n = 15 triads), bystanders witnessed their
      prior dominant being defeated by a stranger before being introduced to them. In a
      second condition (C1, n = 16 triads), bystanders witnessed the victory of their
      prior dominant over a stranger. In a third condition (C2, n = 15 triads),
      bystanders witnessed two strangers establishing a dominance relationship before
      being introduced to their prior dominant and to a stranger the former had just
      defeated. The behavioural strategies of bystanders depended on the issue of the
      conflict they had witnessed. Bystanders of the E condition behaved as having no
      chance of defeating the stranger. They never initiated an attack against it, and
      upon being attacked, readily submitted in turn to the stranger. On the contrary,
      bystanders of the C1 condition behaved as having some chances against the
      stranger. They initiated attacks in 50% of cases, and won 50% of conflicts
      against the stranger. Under condition C2, bystanders first initiated contact with
      the strangers in only 27% of cases, which approximates the average of their
      chances for defeating the stranger. However, bystanders finally defeated the
      strangers in 40% of cases. These results suggest that bystanders of conditions E
      and C1 gained some information on the relationship existing between their prior
      dominant and the stranger and that they used it coherently, perhaps through
      transitive inference, thus contributing to the existence of transitive
      relationships within the triads. Alternate explanations are examined. 

PMID- 24896485
TI  - Resistance to change as a function of concurrent reinforcer magnitude.
AB  - Six pigeons responded on two keys in each of three signalled multiple-schedule
      components, and resistance to disruption of responding on one (target) key by
      extinction and by response-independent food presented during inter-component
      blackouts was studied. Alternative reinforcement of different magnitudes was
      contingent on pecking a non-target key in two components, and in the third only
      the target response was reinforced. Resistance to change varied with the overall
      quantity of reinforcement in the component, regardless of whether reinforcers
      were contingent on the target or non-target response, but did not differ across
      the two key locations. These results using different magnitudes of reinforcement
      confirm previous findings using rate of reinforcement as the variable, and
      suggest that resistance to change is dependent on stimulus-reinforcer rather than
      response-reinforcer contingencies. 

PMID- 24896486
TI  - Visual stimulus compounding with pigeons.
AB  - Eight pigeons responded to successively presented color and line stimuli
      correlated with different likelihoods of reinforcement (100, 50 and 10%). An
      intertriai interval was included during training for half of the birds. In
      Experiment 1, tests with superimposed compounds resulted in variable responding,
      but overall, rates of responding were intermediate to the rates controlled by the
      individual component stimuli. In Experiments 2a and 2b, tests with compounds of
      spatially separated stimuli yielded rates of responding that were intermediate
      to, and in some cases lower than, responding controlled by the individual
      component stimuli. These results suggest limitations to the generality of
      additive models of stimulus compounding when visual stimulus combinations are
      employed. 

PMID- 24896487
TI  - The effect of competition on choice by pigeons: foraging rate, resource
      availability and learning.
AB  - The effect of competition on food choice by pigeons was examined in a within
      subject laboratory study. Pigeons foraged on maize (the more preferred item) and
      wheat (the less preferred item) in two conditions: alone and with a competitor.
      Over the course of the experiment an effect of competition on individual choice
      developed: the pigeons came to choose less maize before the first grain of wheat
      was taken, and to show a higher proportion of choices of wheat. The effect of
      competition was entirely due to resource availability: no effect of the
      competitor per se was found once the number of grains of maize and wheat
      available for any one choice was taken into account. Choice behaviour changed
      over time because the birds learned to forage faster in competition, which in
      turn led to faster depletion rates. 

PMID- 24896488
TI  - The role of individual differences in the formation of triadic dominance orders
      of male green swordtail fish (Xiphophorus helleri).
AB  - Triads of Xiphophorus helleri males composed of a large prior winner (A), a small
      prior winner (alpha), and a small prior loser (omega) were formed. In one
      condition, A was used as bystander while in another condition it was the small
      omega. The bystander could see through a transparent partition and observe
      conflict settlement between the two other fish without interacting with them. As
      soon as a dominance relationship clearly emerged, the partition was raised and
      the fish on standby could establish dominance relationships with them. The most
      frequent triadic structures obtained were A ? alpha ? omega and A ? omega ?
      alpha, indicating that individual characteristics played a determinant role in
      hierarchy formation. Patterns of assembly depended on individual differences of
      the fish. The fact that the same dominance structures were reached through
      various patterns of assembly suggests that individual differences are more
      determinant than paths of resolution in Xiphophorus. 

PMID- 24896489
TI  - Factors affecting the regurgitation behaviour of the ant Lasius flavus
      (Formicidae) to the guest beetle Claviger testaceus (Pselaphidae).
AB  - Workers of regularly fed Lasius flavus ants regurgitate ingluvial food on the
      mouthparts of the guest beetle Claviger testaceus in response to the licking of
      particular secretions of the myrmecophile. These regurgitations typically occur
      with the workers' mandibles joined and antennae immobile, in a U-shaped position,
      even if the colony's diet consists exclusively of insect meat or of a low
      concentrated (2.5%) sugar solution. In addition, when the dietary sugar
      concentration exceeds 5%, workers may disgorge spontaneously, with mandibles
      spread apart and antennae folded backwards, the funiculi divergent. Replete
      (i.e., over-fed) ants present the same spontaneous behaviour. The ratio of the
      number of regurgitations to the number of licking sessions on the Claviger's
      mouthparts is the highest in workers with a moderately filled crop. Such workers
      therefore provide the beetle with the greatest number of regurgitations. Repletes
      and, of course, starving workers provide less regurgitations to the beetle. The
      quantity of liquid food regurgitated on the Claviger also appears to be maximum
      in workers with a moderately filled crop. The workers' regurgitation rate is
      higher in laboratory colonies collected from the field and kept for some months
      than in colonies only recently collected. This effect may be linked to the
      overall age of the worker populations of the laboratory nests. The presence of a
      queen does not affect the workers' regurgitation rate. However, her presence does
      increase the number of workers' licking sessions in mature colonies only recently
      settled in a laboratory and, consequently, increases to some extent the number of
      regurgitations on the beetle. 

PMID- 24896490
TI  - Three-dimensional wax patterning of paper fluidic devices.
AB  - In this paper we describe a method for three-dimensional wax patterning of
      microfluidic paper-based analytical devices (MUPADs). The method is rooted in the
      fundamental details of wax transport in paper and provides a simple way to
      fabricate complex channel architectures such as hemichannels and fully enclosed
      channels. We show that three-dimensional MUPADs can be fabricated with half as
      much paper by using hemichannels rather than ordinary open channels. We also
      provide evidence that fully enclosed channels are efficiently isolated from the
      exterior environment, decreasing contamination risks, simplifying the handling of
      the device, and slowing evaporation of solvents. 

PMID- 24896491
TI  - Male reproductive tactics and reproductive success of the group-living feral cat
      (Felis catus).
AB  - Male reproductive tactics and reproductive success of the feral cat (Felis catus)
      were investigated in a group-living cat population on a small island. Two main
      reproductive tactics depending on body weight were clearly documented. Heavier
      (dominant) males used the tactics of courting not only the females of their own
      group, but also the females of a group other than their own. On the other hand,
      lighter males mainly utilized the tactics of courting only females of their own
      group. However, the former tactics were expected to be unsuccessful from the
      observation that extra-group copulations were rare because of their decreased
      courtship rank during extra-group visits. Results for the paternity of kittens
      obtained by the analysis of polymorphic microsatellite DNA revealed that more
      than half of the kittens of grouping females were fathered by extra-group males,
      suggesting that the tactics were more successful than expected. This discrepancy
      between the observed copulation and the actual paternity also suggesting the
      probability that some female choice may be operating upon the mating system of
      this group-living cat population. 

PMID- 24896492
TI  - Aggressive behaviour of two swordtail colour breeds (Xiphophorus, Poeciliidae) in
      a prior residence situation.
AB  - Males of two swordtail colour breeds (Xiphophorus) were tested for differences
      related to aggression in a prior residency situation. The median latency time of
      the first dominance sign, the first attack, and the first approach was
      significantly shorter in the red than in the black breed, while these differences
      were not present when resident and newcomer or the larger and the smaller member
      of the pair were compared, either in the two breeds separately, or in the two
      breeds combined. The significance of these differences in agonistic behaviour is
      discussed in relation to resource holding power and colour variants in fish. 

PMID- 24896493
TI  - Lateralization of visual guided behaviour during feeding in zebra finches
      (Taeniopygia guttata).
AB  - The aim of the study was to investigate the asymmetries of visual discrimination
      performance in zebra finches. Adult male and female zebra finches were tested on
      the pebble floor test, where the subjects must distinguish between beads and food
      grains under monocular conditions after a period of food deprivation. Left-eyed
      birds pecked at beads more than right-eyed and binoculars, but only during the
      last part of the test. The better performance of the right-eyed birds can be
      understood as the higher ability of the left hemisphere of the brain to
      categorize food, as has been already suggested for chicks and pigeons.
      Nevertheless, the absence of differences at the beginning of the task support the
      hypothesis of different modes of information processing, such as a prominent
      involvement of the right hemisphere in response to novelty. 

PMID- 24896494
TI  - Play fighting in juvenile golden hamsters (Mesocricetus auratus): Effects of
      litter size and analysis of social interaction among males.
AB  - Previous studies have shown that different social experiences, such as the
      interaction involving partners of different ages or among individuals of
      different sexes, significantly alter the play rate. In the present study, two
      experiments are described, the hamster being used as subject, to investigate the
      effects of litter size and to analyse the play fighting behavior among males. It
      was found that there was no significant difference in the time spent in play
      fighting by an animal when it was placed in groups of 2, 4 or 6 individuals (Exp.
      1). Moreover, the majority of animals did not show preferences during play
      fighting when they were placed in groups formed by four males (Exp. 2). Through
      these data it has been noted that the hamster distributes the total time spent in
      play fighting among the available partners. This fact can be explained by the
      hamster's social organization, because it is a solitary animal, which does not
      develop a clear and durable interaction with its playmates. Also, through other
      results, a certain stability was found in most of the behavioral categories
      registered such that they were not significantly affected by the manipulated
      variables. 

PMID- 24896495
TI  - Range effects and dimensional organization in visual discrimination.
AB  - Pigeons were trained to discriminate two types of visual forms that could vary in
      two orthogonal dimensions. One set of stimuli was designed to have relatively
      integral dimensions, while the other set of stimuli was intended to have
      relatively separable dimensions, for the pigeon. A first experiment provided
      evidence that the dimensions of our two stimulus sets differed in the degree of
      separability. The second experiment examined the effect of increased stimulus
      range on discrimination of the two stimulus sets. Results from this experiment
      indicated that increases in range in either relevant or irrelevant dimensions
      reduced discrimination for the integral stimulus set. For the separable stimulus
      dimensions, however, performance declined only with increased stimulus range
      along a relevant dimension. In the third experiment, stimulus range was increased
      along either one or two dimensions of the stimulus. Correlated changes in
      stimulus range along two dimensions had an impact only for integral stimuli. In
      summary, these experiments demonstrate that the organizational structure of
      stimulus dimensions determines the impact of increases in stimulus range,
      probably due to the attentional properties of different stimulus forms. 

PMID- 24896496
TI  - Intradimensional transfer of duration matching-to-sample in pigeons with signals
      differing in color and location.
AB  - Duration matching-to-sample (MTS) was used to study the influence of signal
      attributes on temporal transfer in pigeons. Each of two groups was trained on two
      problems that involved 2 and 10 s duration samples that varied with respect to
      color and-or spatial location. For Group Color, signals were either a red or
      white light projected from the front wall. For Group Location, signals were a
      white light from either the front wall or the ceiling. Within each group, each
      combination of signal type (color or location) and duration was associated with a
      different choice stimulus, and one set of color choices always followed one
      signal type and a different set of color choices always followed the other signal
      type. Transfer tests involved a set of choices that had not previously been
      associated with the type of signal presented on that trial. Accuracy on transfer
      trials was very high in Group Color but at a chance level in Group Location,
      which indicates that temporal transfer occurs when signals emanate from the same
      location but not when signals emanate from different locations. These results are
      discussed in terms of other evidence of transfer of duration-MTS. 

PMID- 24896497
TI  - Behavioural control by simultaneous and serial features in feature-positive and
      feature-negative discriminations.
AB  - Two experiments with rats examined behavioural control by feature stimuli in
      appetitive conditioning using latency of food-magazine visits as the dependent
      measure. In experiment 1, a feature-positive (FP) discrimination was presented in
      which a target stimulus was consistently followed by food when preceded by a
      serial feature and accompanied by a simultaneous feature, and not followed by
      food when presented alone. The reverse condition, a feature-negative (FN)
      discrimination procedure, was in effect in experiment 2. Groups of rats differed
      in the physical identity of the stimuli used as target and features. In the FP
      discrimination, all groups came to respond faster on reinforced than on
      nonreinforced trials. Subsequent tests revealed that the serial feature was
      responsible for this performance in all groups, whereas the simultaneous feature
      had not acquired significant control in all groups. Only one half of the groups
      solved the FN discrimination and they did this on the basis of only the
      simultaneous feature, which was a relatively intense stimulus in these groups.
      These results suggest a propensity to use the serial feature in FP
      discriminations and the simultaneous feature in FN discriminations. 

PMID- 24896498
TI  - Exposure to context may contribute to within-session changes in responding.
AB  - Rats and pigeons responded on multiple variable interval 30-s variable interval
      30-s and multiple variable interval 60-s variable interval 60-s schedules. The 60
      min sessions began 0, 5, 10, 15 or 30 min after the subject was placed in the
      experimental enclosure, determined randomly. Early-session response rates were
      usually higher, and the early-session increases in responding were usually
      smaller, when the beginning of the session was delayed than when it was
      immediate. These results show that factors related to reinforcement (e.g.
      satiation, sensitization-habituation to the reinforcers) do not provide a
      complete explanation for within-session changes in operant responding. Instead,
      an additional factor, possibly arousal or sensitization to the experimental
      context, also contributes. The results suggest an explanation for the spontaneous
      recovery of extinguished behavior. 

PMID- 24896499
TI  - Evidence for a specific short-term memory in the cuttlefish, Sepia.
AB  - Cuttlefish quickly learn to inhibit their predatory motor pattern when shown
      prawns in a glass tube. The available literature suggests that cuttlefish show an
      excellent retention between 2 and 8 min, a recovery of the predatory responses
      around 20 min and good retention after 1 h of the training phase. These results
      have been considered as the product of two separate short- and long-term memory
      stores. In this study, we have investigated the fact that the retention seen
      after a brief delay of the training phase corresponds to a true effect of
      learning. We compared animals under three experimental conditions. In two, there
      was a unique training trial of different duration (5 or 20 min), a third group
      served as controls. Our results demonstrate that the control situation failed to
      reduce the level of attack; in contrast the short-term retention, obtained after
      a single learning trial, is related to a specific short-term memory process. 

PMID- 24896500
TI  - Silica morphogenesis by lysine-leucine peptides with hydrophobic periodicity.
AB  - The use of biomimetic approaches in the production of inorganic nanostructures is
      of great interest to the scientific and industrial community due to the
      relatively moderate physical conditions needed. In this vein, taking cues from
      silaffin proteins used by unicellular diatoms, several studies have identified
      peptide candidates for the production of silica nanostructures. In the current
      article, we study intensively one such silica-precipitating peptide, LKalpha14
      (Ac-LKKLLKLLKKLLKL-c), an amphiphilic lysine/leucine repeat peptide that self
      organizes into an alpha-helical secondary structure under appropriate
      concentration and buffer conditions. The suggested mechanism of precipitation is
      that the sequestration of hydrophilic lysines on one side of this helix allows
      interaction with the negatively charged surface of silica nanoparticles, which in
      turn can aggregate further into larger structures. To investigate the process, we
      carry out 1D and 2D solid-state NMR (ssNMR) studies on samples with one or two
      uniformly (13)C- and (15)N-labeled residues to determine the backbone and side
      chain chemical shifts. We also further study the dynamics of two leucine residues
      in the sequence through (13)C spin-lattice relaxation times (T1) to determine the
      impact of silica coprecipitation on their mobility. Our results confirm the alpha
      helical secondary structure in both the neat and silica-complexed states of the
      peptide, and the patterns of chemical shift and relaxation time changes between
      the two states suggest possible mechanisms of self-aggregation and silica
      precipitation. 

PMID- 24896501
TI  - All-nano-TiO2 compact film for high-performance dye-sensitized solar cells.
AB  - An innovative all-nano-TiO2 thin film capable of enhancing dye-sensitized solar
      cell (DSC) photoefficiencies was prepared by a layer-by-layer method beneath the
      meso-TiO2 film, employing acid and basic nano-TiO2 sols as cations and anions,
      respectively. TiO2 syntheses were performed under absolute control to lead to
      appropriate morphological and optical properties to yield high-quality compact
      films using profilometry, tuning, and scanning electron microscopy. A detailed
      study by photoelectrochemical parameters, incident photon-to-current efficiency,
      electron lifetime, and electrochemical impedance spectroscopy demonstrates that
      the physical contact between FTO and the electrolyte is prevented and the role of
      the compact film has been elucidated. DSCs with TiO2 bilayers on top of FTO
      improved the conversion efficiency up to 62%, mainly because of the prevention of
      FTO/I3(-) charge recombination and an improved contact between FTO and TiO2. 

PMID- 24896502
TI  - Fluorescent RNA labeling using self-alkylating ribozymes.
AB  - The ability to fluorescently label specific RNA sequences is of significant
      utility for both in vitro and live cell applications. Currently, most RNA
      labeling methods utilize RNA-nucleic acid or RNA-protein molecular recognition.
      However, in the search for improved RNA labeling methods, harnessing the small
      molecule recognition capabilities of RNA is rapidly emerging as a promising
      alternative. Along these lines, we propose a novel strategy in which a ribozyme
      acts to promote self-alkylation with a fluorophore, providing a robust, covalent
      linkage between the RNA and the fluorophore. Here we describe the selection and
      characterization of ribozymes that promote self-labeling with fluorescein
      iodoacetamide (FIA). Kinetic studies reveal a second-order rate constant that is
      on par with those of other reactions used for biomolecular labeling.
      Additionally, we demonstrate that labeling is specific to the ribozyme sequences,
      as FIA does not react nonspecifically with RNA. 

PMID- 24896503
TI  - The behavioural and reproductive consequences in offspring (first generation) of
      mice continuously exposed to a strong magnetic field.
AB  - The behavioural and reproductive activities of the offspring of mice that had
      spent their whole lives exposed to a continuous strong magnetic field (76655
      gamma) were investigated. The data obtained revealed that intermale fighting was
      drastically inhibited in such animals. Exposure to such a condition also
      significantly reduced other behavioural responses (e.g. social and non-social
      elements) recorded in the social encounters between experimental and 'standard
      opponent' intruders. Preliminary results on the reproductive activity of exposed
      mice were evaluated by mating them with female counterparts which had also spent
      their whole lives under the same condition of the magnetic field intensity. None
      of the mated females became pregnant. The magnetic field thus influences the
      behavioural and reproductive responses in mice. These effects may be mediated by
      their influences on the neurophysiological sites that control these activities. 

PMID- 24896504
TI  - Relative size and agonistic behaviour in the female velvet swimming crab, Necora
      puber (L.) (Brachyura, Portunidae).
AB  - Female velvet swimming crabs (Necora puber) fight readily in the laboratory, with
      interactions being initiated equally often by the larger and smaller of the two
      opponents, but with the larger usually being victorious. In 17 out of 65
      interactions, however, a smaller crab won against a larger one, and possible
      reasons for this are discussed. In two respects our results are surprising in the
      context of insights gained from games theory: firstly, the fights do not show a
      gradual pattern of escalation through display to overt physical violence; and
      secondly, fights do not become more costly in terms of either potential for
      injury (intensity) or duration as the contestants became more evenly matched;
      indeed, as the contestants became more evenly matched, fight duration decreased. 

PMID- 24896505
TI  - Temporal generalizations in humans: Three further studies.
AB  - Three experiments investigated human performance on variants of the temporal
      generalization procedure developed by Wearden (1992) from an experiment with
      animals by Church and Gibbon (1982). All experiments used short tone durations as
      stimuli to be judged, and chronometric counting was not spontaneously used by
      subjects. Experiment 1 studied the effects of extended exposure to a temporal
      generalization procedure, with a 400 ms standard duration. With increasing
      exposure, subjects' tendency to produce judgemental asymmetries (i.e. confusing a
      500 ms stimulus more with the standard than a 300 ms one, a standard result in
      temporal generalization with human subjects) decreased, and this was modelled
      theoretically by assuming that subjects came to adopt stricter response criteria
      for durations longer than the standard than those which were shorter. Experiment
      2 used standard durations which were at the end of a stimulus set ranging from
      200 to 800 ms. Orderly generalization functions were obtained in these cases, and
      data were well-fitted by a standard model of temporal generalization. Experiment
      3 used an 'episodic' variant of temporal generalization, involving the comparison
      of the durations of 2 stimuli present on a trial. Once again judgemental
      asymmetries were found, but standard models of temporal generalization failed to
      fit data from some cases. Overall, both experimental effects and theoretical
      treatments from temporal generalization studies were robust in the face of
      procedural variations. 

PMID- 24896506
TI  - Intersexual conflict over precopula duration in mate guarding crustacea.
AB  - Precopulatory guarding in Crustacea is usually analyzed as a male decision
      problem. We suggest an alternative possibility that precopula is established as a
      result of intersexual conflict over precopula duration. Such a conflict can be
      expected when the male optimum for precopula duration exceeds the female optimum.
      As a result, males should start precopulatory attempts earlier, while females
      should resist until close to receptivity. Our analysis reveals two potential
      sources of conflict: (1) sexual differences in survival probabilities before and
      during the mate-guarding; and (2) sexual differences in the probability of
      finding a mate. The latter is perhaps a more probable source of intersexual
      conflict, since male biased operational sex ratios are common in mate-guarding
      Crustacea. The former requires that female moulting cycle is synchronous, whereas
      the latter may operate in populations with asynchronous moulting cycles as well.
      We further studied the expected intensity of behavioural conflicts in terms of
      expected present and future fitness gains. In the beginning of the female
      moulting cycle, there is no conflict. Conflict arises as males start the guarding
      attempts and females are motivated to resist, and ceases with a decrease in the
      female's motivation to resist. Several assumptions and predictions of the model
      are discussed and compared with the behavioural patterns observed in the aquatic
      isopod Idotea baltica. 

PMID- 24896507
TI  - Effects of age, sex, and odours from conspecific adult males on ultrasonic
      vocalizations of infant CS1 mice.
AB  - Young CS1 mice aged 2, 4, 6, 8 and 10 days were each sequentially exposed to
      odours of urine from strange adult infanticidal and non-infanticidal males and
      the number of ultrasonic vocalizations monitored. There was a clear age effect,
      with pups 6-8 days calling the most. For pups of 2 and 6 days of age there were
      significant positive correlations between body weight and number of calls but for
      10-day-old pups a negative correlation was found. Female pups called more than
      males, particularly when exposed to odours but this was not due to body weight.
      Overall, more calls were produced when odours from infanticidal rather than non
      infanticidal males were presented and individual pups altered their ultrasonic
      output as the odours were changed. 

PMID- 24896508
TI  - Experience of defeat decreases the behavioural reactivity to conspecifics in the
      partition test.
AB  - The partition test was used to estimate behavioural reactivity of male mice to
      conspecifics. Paired males were placed in the neighbouring compartments of a
      common cage separated into halves by a transparent partition with holes
      permitting animals to see and smell each other but preventing physical contact.
      Winners (with long experience of victories in daily inter-male confrontations)
      approached the partition and spent longer near it reacting to the partner in the
      neighbouring compartment than losers with long experience of defeat. Five defeats
      of winners in agonistic confrontations with stronger aggressive individuals led
      to a decrease of behavioural activity near the partition. Losers did not notice
      unfamiliar males in the next compartment. Under such conditions, winners or
      intact males significantly increased parameters of behavioural reactivity near
      partition to an unfamiliar neighbour. The data obtained are discussed in terms of
      decrease of the loser's behavioral reactivity to conspecifics as a result of the
      experience of defeat in social confrontations leading to the development of
      anxiety or, possibly, of failure of olfactory perception. 

PMID- 24896509
TI  - Spatial organization of roosting in the insectivorous tropical bat Hipposideros
      speoris.
AB  - The roost organization of the insectivorous bat Hipposideros speoris was studied
      both in the field and in conditions of captivity. All the individuals roost
      singly and maintain a marked fidelity to their roost sites for long periods. The
      males use their urine as an olfactory cue in relocating their respective roost
      sites but the females appear to relocate their roost sites relatively by
      recognizing the position of neighbouring conspecifics. In captivity all the
      individuals prefer to roost in darker regions of the cage, which resulted in the
      formation of a hierarchical order of roosting. Experiments with captive bats
      revealed a greater ability to reorientate towards their roosting sites in males
      than in females. The individuals rigidly guard their roosting sites by displaying
      agonistic behaviour toward intruders. Such a site-specific pattern of roosting
      seems to serve the function of accommodating many individuals within a small
      space available in an organised manner. 

PMID- 24896510
TI  - [Not Available].
AB  - Data from previous experiments on predator-prey distance estimation during
      ontogeny are compared to theoretical interpretations. In Ranatra the
      relationships between performance (maximum reactive distances), effectors (length
      of forelegs) and receptors (eyes) do not remain constant during nymphal
      development, contrary to Mantids (Maldonado et al., 1973). The hypothesis of an
      automatic morphological adaptation occurring after each moult cannot be retained.
      Burkhardt et al.'s (1973) theoretical analysis of binocular vision in insects was
      applied to Ranatra : for the first four nymphal instars, the calculated limits of
      binocular vision coincide with maximum reactive distances. This could explain why
      these animals do not react to prey items presented at distances equal to the
      length of their forelegs before the 5th instar. The theoretical limits of
      binocular vision are further away than the maximum capture distances and the
      length of their forelegs for 5th instar nymphs and adults ; the length of their
      forelegs would then limit capture possibilities. 

PMID- 24896511
TI  - Probable functions for a previously unrecognized pheromone in ants of the genus
      Myrmica.
AB  - A previously unknown pheromone has been detected in workers of Myrmica rubra when
      an extract, usining a polar solvent, of the VIIth abdominal sternite was shown to
      attract ants over short distances and to act in synergy with the trail pheromone
      to enhance its effect. This new factor has now been shown to help the foraging
      workers to distinguish between recent and older trails and to confer on the
      trails a species-specific character (demonstrated for five species of Myrmica )
      that the trail pheromone alone does not possess. 

PMID- 24896512
TI  - [Not Available].
AB  - The mating was studied for a cave-living Coleoptera Bathysciinae, Speonomus
      delarouzeei , and consists of three behavioural units : a short pre-mating phase
      (55 s), a short resting phase (50 s) and a longer mating phase (5 min 20 s). When
      the female is in a receptive condition, numerous matings occur, separated by a
      more or less long time ; between the copulations the male remains behind the
      female, both forming thus a "pair" which may last 48 hours. One female can
      copulate successively with several males. The males behavior which always follow
      the females between two matings allows to think that a female pheromone is
      produced and stimulates the males at a very short distance. 

PMID- 24896513
TI  - Measures of space in pairs of hens in battery cages.
AB  - An experiment was designed to test whether distances between 2 hens depend on the
      amount of available space in a cage. Interindividual distances were recorded as
      well as contact behaviour since it represents the most extreme reduction of
      interindividual distance. Pairs of hens from 2 strains (Rhode Island Red x White
      Plymouth and White Leghorn) were observed in cages of a battery-like system. The
      experimental schedule was: 1 week at initial densities; 10 weeks at changing
      densities; 1 week at final densities which were identical to the initial ones.
      The initial conditions were Small (900 cm(2)/bird), Medium (1400 cm(2)/bird) and
      Large (1900 cm(2) /bird). Each of these conditions was gradually changed to two
      intermediate conditions by means of successive weekly density increases or
      decreases (100 cm(2)/ bird) for 5 weeks: thereafter, the final densities were
      restored by successive weekly decreases or increases. The intermediate conditions
      were: Very Small (400 cm(2)/bird) or Medium (1400 cm(2)/bird) for small cages;
      Small (900 cm(2)/bird) or Large (1900 cm(2)/bird) for medium cages and Medium
      (1400 cm(2)/bird) or Very Large (2400 cm(2)/bird) for large cages. It was found
      that the larger the cages, the larger were the interindividual distances. Thus,
      it is the objective space which determines the occupation of a cage; hens do not
      use all the available space in their cage at any density. Contact behaviour was
      more frequent in the smaller the cages. The results are discussed in the context
      of welfare with regard to the minimum space required by laying hens in battery
      cages. Recommendations are made on the basis of the average distances which were
      recorded in all the experimental conditions. 

PMID- 24896514
TI  - Observations on pushing and aggression in pairs of hens in battery cages.
AB  - An experiment was designed to test in two strains of chickens whether aggression
      and pushing behaviour in pairs of hens depended on the amount of available space
      in battery cages. There was essentially no aggression and cage areas had no
      effect on the frequency of aggressive pecks. Pushing behaviour (which was
      reciprocal) was often observed in the battery cages, but its frequency was not
      affected by density. Most results were similar for the 2 strains. Post
      experimental observations confirmed these results. Feather-pecking was largely
      absent in pairs of the light strain whereas it was significantly affected by
      floor area in pairs of the medium strain, i.e. most frequent at intermediate cage
      areas. Inter-cage aggressive pecks were significantly more frequent than intra
      cage ones. 

PMID- 24896515
TI  - Brood care motivation and hunger in the mouthbrooding cichlid Pseudocrenilabrus
      multicolor.
AB  - The interrelationship of hunger and brood care motivation was investigated in the
      mouthbrooding cichlid Pseudocrenilabrus multicolor from East Africa. In this
      species the female takes up her eggs during spawning and carries them
      continuously in her buccal cavity for approximately 10 days (at 27 degrees C).
      Females with brood in their mouths do not eat. If the brood is removed from the
      female's mouth at varied times after spawning, brood care motivation (BM) -
      defined as the readiness to keep brood in the mouth and not to eat it - is
      maintained for several days (as in most first spawners) or disappears within a
      few hours (as in most non-first spawners). Hunger - as measured by the amount of
      Tubifex ingested per unit time - depends on whether the brood-deprived female
      exhibits BM or not: females without BM eat as much as non-brooding control
      females. Females with BM eat only approximately half as much. This is true for
      first spawners as well as for non-first spawners. It can be concluded that a
      complete physiological anorexia is not needed to prevent brood-eating in
      mouthbrooding females. A substantial lowering of the general satiation level is
      sufficient. In addition, stimuli from the brood in the female's mouth totally
      inhibit food ingestion from outside the mouth during mouthbrooding. 

PMID- 24896516
TI  - Selective effects of post-imprinting anaesthesia on choice-test behaviour.
AB  - Day-old chicks which are submitted to a halothane anaesthesia immediately after a
      10 min. exposure to a moving model are less likely than non-treated chicks to
      approach this model in subsequent tests given 24 and 48 hours later. They may be
      unable to approach any model or they may approach the other model presented in
      the test situation. Modulation of responses at test depends on strength of
      imprinting which itself depends on attractiveness of the model and amount of
      following displayed during the exposure session. Results of this experiment
      corroborate previous results showing disruptive effects of halothane anaesthesia
      on behaviour in imprinted chicks, effects which are stronger if chicks had a poor
      visuo-motor experience at exposure session. Imprinting as a gradual acquisition
      process is suggested by detailed analysis of results of control and treated
      chicks. 

PMID- 24896517
TI  - An environmental limit on absolute auditory sensitivity in non-aquatic
      vertebrates.
AB  - It is proposed that ambient noise of environmental origin ultimately limits, at a
      common level, the lowest auditory thresholds found in both the non-aquatic
      mammals (including man) and in the most sensitive birds, the owls (Strigiformes).
      Greater sensitivity than that found in these vertebrates is unlikely to have
      evolved since it would be of little or no adaptive value. However, whether
      sensitivity in a particular species actually approaches this limit depends upon
      the species' evolutionary origins, and upon its period of activity within the
      day. 

PMID- 24896518
TI  - Sibling recognition in the rook (Corvus frugilegus ).
AB  - In this study we tested whether rook siblings were able to recognize each other
      vocally when 2-2 1 2 months-old and, if so, whether this recognition still
      persisted about 10 months later. Twelve rook nestlings were hand-reared. Vocal
      recognition by the young birds (aged 2-2 1 2 months) was tested. The birds
      responded significantly more frequently to the call of a sibling than to the call
      of a non-sibling. This indicates that audible cues are at least important for
      sibling recognition. The individual rooks were thereafter visually isolated, in
      12 individual cages, for a further 10 months. The birds were then put together in
      an aviary and their social relationships studied. Siblings were significantly
      less aggressive towards each other than towards non-siblings and siblings
      remained close together significantly more often than non-siblings. The
      significance of sibling recognition is discussed. 

PMID- 24896519
TI  - Effects of relative proximity to reinforcement of a stimulus intruded on fixed-
      and variable-ratio schedules of reinforcement.
AB  - Pigeons were trained to respond on either a fixed- or a variable-ratio schedule
      of reinforcement. After responding had stabilized, a visual stimulus change was
      presented after either 20% or 80% of the ratio had been completed. The duration
      of the stimulus was equal to the time it took the subjects to complete an
      additional 10% of the ratio. Presentation of the stimulus early in the ratio
      inhibited responding on the variable, but not on the fixed-ratio schedule. A
      stimulus change after 80% of the ratio had been completed, only produced response
      enhancement on the variable-ratio schedule. The effects of stimulus intrusion on
      ratio schedules were determined by a) the temporal proximity between stimulus
      intrusion and reinforcement presentation, and b) the contingencies of the operant
      baseline. 

PMID- 24896520
TI  - The role of familiarity in the development of social preferences in spiny mice.
AB  - A series of experiments investigated the role of familiarity in the development
      of individual recognition and social preferences in spiny mice. Pups who suckled
      from the same mother were able to recognize one another by common maternal labels
      even though these same pups were also differentially labeled by additional
      females. However, maternal labels appear to be less salient for the development
      of social preferences than is familiarization of pups through direct exposure.
      The manner in which animals are exposed to one another affects the
      familiarization process. Weanlings exposed to one another in the dark were
      similar to animals housed under a light/dark cycle in subsequent tests of
      recognition. In comparison to animals separated by wire mesh, those allowed
      complete physical contact subsequently displayed more positive social behavior.
      Therefore, while visual familiarity is not necessary for subsequent recognition,
      the familiarization process is facilitated by the opportunity for bodily contact.
      Recognition is probably mediated by olfactory cues, moreover, the social
      environment also influences the development of conspecific recognition. Animals
      housed with vs. without littermates while being exposed to unfamiliar agemated
      differed in later tests with the latter animals. 

PMID- 24896521
TI  - Experimental novelty and tonic immobility in chickens (Gallus domesticus ).
AB  - The tonic immobility reactions of individually-caged adult hens were observed in
      familiar or novel environments when the experimenter wore either a familiar or
      unfamiliar coat. Birds tested in isolation in an unfamiliar environment showed
      longer tonic immobility than did those tested in their familiar environment where
      they could still see and hear their neighbours. Tonic immobility was
      significantly prolonged in both test environments if the experimenter wore an
      unfamiliar coat. The potentiation of tonic immobility by novel aspects of the
      experimenter's appearance may thus be superimposed upon that elicited by social
      isolation and novelty of the physical environment. 

PMID- 24896522
TI  - Injection of a neuroleptic produces changes in caregiver-infant interactions in
      marmosets.
AB  - The effects of injecting a low dose of the neuroleptic fluphenazine decanoate
      (MODECATE) on the responsiveness of family members (fathers and siblings) to
      infant common marmosets (Callithrix jacchus ) are described. Tentative
      conclusions are that the overall effect of the injection is to make fathers and
      siblings more 'passive' and unresponsive, though the detailed effects are complex
      and not all interactions with infants are affected. Drugged fathers spend less
      time grooming infants, pick them up more infrequently, and approach and leave
      them less often than undrugged fathers. Drugged siblings spend less time playing
      with infants, ignore them more often, and approach and leave them less often than
      undrugged siblings. These results indicate the need for studies of the effects of
      drugs on normal behaviours as well as studies of their side-effects or
      therapeutic efficacy. 

PMID- 24896523
TI  - Behavioural development of the gardendormouse, Eliomys quercinus L. : II) an open
      field study.
AB  - In order to study the behavioural development of the gardendormouse the open
      field method was used. Each young dormouse was tested for 3 minutes every day.
      Locomotion, urination, defecation and vocalizations were recorded and quantified.
      The tests were made from birth to the 30 th day of life. The locomotory activity
      increased progressively and reached a maximum on the 28th day. From birth to the
      18th day of life the number of whistles emitted by the young dormice increased as
      the locomotory activity did. After the 18th day the number of the whistles
      decreased quickly. Then a negative correlation was observed between the number of
      whistles and the locomotion, the urination and the defecation activities. The
      results are discussed with reference to other developmental aspects of the
      gardendormouse. 

PMID- 24896524
TI  - Recognition of prey species by their odors in the grasshopper mouse (Onychomys
      leucogaster ).
AB  - This study examined the development of olfactory recognition of an insect prey by
      the northern grasshopper mouse. The approach was to feed different groups of mice
      a certain amount of house crickets, may beetles or mealworm larvae or varying
      numbers of house crickets and then measure a mouse's preference for discovering
      that particular species when presented these three insects buried in a grid
      pattern. A mouse preferentially sought out that species which it had eaten and
      required between 5 and 15 prior feeding experiences to develop that preference. 

PMID- 24896525
TI  - Sexual behaviour of juvenile male rats injected with lisuride.
AB  - Lisuride was reported as drug stimulating sexual behaviour in the adult male
      rats. It was stated that lisuride is effective through central serotonergic and
      dopaminergic systems. The present study deals with the effects of lisuride on the
      sexual behaviour of juvenile Wistar male rats, 43 days old. The animals were
      injected i.p. with lisuride /0.4 mg/kg/ or saline 40 min prior to testing. When
      the males were put into a box with the floor prescented by an oestrous female,
      the males treated with lisuride devoted significantly more time to the sniffing
      of the scent traces. After a darting female was placed into the box, some of the
      lisuride injected males initiated copulatory behaviour, even without previous
      precopulatory behaviour towards her. In noncopulating males treated with lisuride
      the frequency of precopulatory activities was comparable with those seen in the
      controls, but the predominance of precopulatory touching the flanks over
      anogenital exploration was suggested. The results are related to those acquired
      in the adult animals. 

PMID- 24896526
TI  - Observations of group introductions in lowland gorillas.
AB  - Data concerning group interactions subsequent to introductions of novel or
      familiar animals comes primarily from studies of a few cercopithecine species.
      This investigation attempted to supplement these data with descriptive
      observationd of gorillas during, and for a period following introductions. A
      unisexual group of females and a heterosexual group were formed. Departures from
      the cercopithecine pattern were observed in terms of the frequency of aggression,
      as well as the time course and the level of agonistic activity following group
      stabilization. Agonism remained high and in one case comprised 80% of the
      interactions six months after the introduction. The female group evidenced
      elevated levels of agonism as well as a possible means of appeasing such
      behaviors. The results are discussed in terms of the apparent absence of a status
      hierarchy in gorillas. 

PMID- 24896533
TI  - Multigenerational effects of maternal undernutrition.
AB  - Intrauterine exposure to reduced nutrient availability can have major effects in
      determining susceptibility to chronic disease later in life. Martinez et al.
      (2014) demonstrate multigenerational effects of poor maternal nutrition and
      evidence of germline transmission through alterations in DNA methylation.

PMID- 24896534
TI  - Father-son chats: inheriting stress through sperm RNA.
AB  - Although mounting evidence in mammals suggests that certain ancestral
      environmental exposures can influence the phenotype in future generations,
      mechanisms underlying such intergenerational information transfer remain unclear.
      A recent report suggests that RNA isolated from sperm can inform offspring of a
      father's history of early life trauma (Gapp et al., 2014).

PMID- 24896535
TI  - Getting pumped about heart failure.
AB  - Heart failure is a clinical syndrome caused by dysregulated calcium handling and
      abnormal cardiac pumping capacity. Wahlquist et al. (2014) show that upregulation
      of microRNA-25 impairs calcium handling leading to pump dysfunction and that
      targeting microRNA-25 using antisense oligonucleotides reverses pump dysfunction
      and improves survival in mice with heart failure.

PMID- 24896536
TI  - IL-6 strikes a balance in metabolic inflammation.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine that exerts either proinflammatory
      or anti-inflammatory effects and is implicated in diverse settings, including
      obesity, exercise, arthritis, and colitis. A new study shows that modulation of
      macrophage activation by IL-6 maintains glucose homeostasis in diet-induced
      obesity while limiting inflammation in endotoxemia (Mauer et al., 2014).

PMID- 24896537
TI  - Fat or fiction: origins matter.
AB  - Cell-lineage tracing has revealed a complex heterogeneity present in postnatal
      tissue and adult progenitors. Chau et al. (2014) and Long et al. (2014) provide
      further evidence for this among adipocytes, and their findings underscore the
      importance of cellular ontogeny not just for development but also for potential
      treatment of disease.

PMID- 24896538
TI  - Stable emulsions formed by self-assembly of interfacial networks of dipeptide
      derivatives.
AB  - We demonstrate the use of dipeptide amphiphiles that, by hand shaking of a
      biphasic solvent system for a few seconds, form emulsions that remain stable for
      months through the formation of nanofibrous networks at the organic/aqueous
      interface. Unlike absorption of traditional surfactants, the interfacial networks
      form by self-assembly through pi-stacking interactions and hydrogen bonding.
      Altering the dipeptide sequence has a dramatic effect on the properties of the
      emulsions formed, illustrating the possibility of tuning emulsion properties by
      chemical design. The systems provide superior long-term stability toward
      temperature and salts compared to with sodium dodecyl sulfate (SDS) and can be
      enzymatically disassembled causing on-demand demulsification under mild
      conditions. The interfacial networks facilitate highly tunable and stable
      encapsulation and compartmentalization with potential applications in cosmetics,
      therapeutics, and food industry.

PMID- 24896539
TI  - Resolution of three cryptic agricultural pests (Ceratitis fasciventris, C.
      anonae, C. rosa, Diptera: Tephritidae) using cuticular hydrocarbon profiling.
AB  - Discrimination of particular species within the species complexes of tephritid
      fruit flies is a very challenging task. In this fruit-fly family, several
      complexes of cryptic species have been reported, including the African cryptic
      species complex (FAR complex). Cuticular hydrocarbons (CHCs) appear to be an
      excellent tool for chemotaxonomical discrimination of these cryptic species. In
      the present study, CHC profiles have been used to discriminate among three
      important agricultural pests from the FAR complex, Ceratitis fasciventris,
      Ceratitis anonae and Ceratitis rosa. Hexane body surface extracts of mature males
      and females were analyzed by two-dimensional gas chromatography with mass
      spectrometric detection and differences in CHC profiles between species and sexes
      tested through multivariate statistics and compared with species identification
      by means of microsatellite markers. Quantitative as well as qualitative CHC
      profile differences between sexes and species are reported. The CHC profiles
      consisted of a mixture of linear, internally methyl-branched and mono-, di- and
      tri-unsaturated alkanes. Twelve compounds were pinpointed as potential
      chemotaxonomical markers. The present study shows that presence or absence of
      particular CHCs might be used in the chemical diagnosis of the FAR complex.
      Moreover, our results represent an important first step in the development of a
      useful chemotaxonomic tool for cryptic species identification of these important
      agricultural pests.

PMID- 24896540
TI  - A prodrug strategy based on chitosan for efficient intracellular anticancer drug
      delivery.
AB  - Doxorubicin (DOX), one of the most widely used anticancer drugs, is restricted in
      clinical application due to its severe side effects and inefficient cellular
      uptake. To overcome the drawbacks, herein, an endosomal pH-activated prodrug was
      designed and fabricated by conjugating DOX with chitosan via an acid-cleavable
      hydrazone bond. The resulting DOX conjugates can self-assemble into nano-sized
      particles, which were very stable and presented no burst release of DOX at a
      neutral pH condition. Notably, the nanoparticles exhibited excellent cell uptake
      properties and a remarkable drug accumulation in tumor cells. Once internalized
      into the cells, moreover, DOX can be fast released from the nanoparticles, and
      the release mechanism changed from the anomalous transport at pH 7.4 to the
      combination pattern of diffusion- and erosion-controlled release at pH 6.0 or
      5.0. The prodrugs showed obvious cytotoxicity for HeLa cells with fairly low IC50
      values, offering a new platform for targeted cancer therapy. 

PMID- 24896543
TI  - Letter from the editor.

PMID- 24896542
TI  - Stress and dementia.

PMID- 24896544
TI  - Clinical phenotypes of castration-resistant prostate cancer.
AB  - Castration-resistant prostate cancer (CRPC) is defined as prostate cancer that no
      longer responds to androgen deprivation therapy. At the genome level, CRPC is a
      heterogeneous disease that is marked by a range of genetic and epigenetic
      lesions. These lesions differ from patient to patient, but have common pathway
      based themes. Clinically, a range of phenotypic presentations or subtypes of CRPC
      are observed that mirror this underlying heterogeneity as the disease progresses;
      each phenotype carries a different prognosis and different implications for
      treatment. In this review, we discuss the clinical subtypes of CRPC based on
      histology; the presence of metastatic disease and pattern of spread; patient
      reported symptoms; and levels of biomarkers, such as serum bone turn- over
      biomarkers, prostate-specific antigen, circulating tumor cell enumeration, and
      neuroendocrine biomarkers. We then address the potential relationship between
      these clinical phenotypes (with their underlying molecular subtypes) and
      therapeutic decision- making and prognosis, as well as ongoing research
      strategies.

PMID- 24896545
TI  - Monoclonal B-cell lymphocytosis: update on diagnosis, clinical outcome, and
      counseling.
AB  - Monoclonal B-cell lymphocytosis (MBL) is a clonal B-cell disorder characterized
      by less than 5 * 109/L B lymphocytes in the peripheral blood, with a
      characteristic immunophenotype and no lymphadenopathy or organomegaly. The vast
      majority of MBL cases express the immunophenotype of chronic lymphocytic leukemia
      (CLL; CLL-like MBL), although non-CLL MBL also exists. CLL-like MBL, which is the
      focus of this review, is divided into low-count MBL (median B-cell count: 0.001 *
      109/L, typically identified in population-based screening studies using highly
      sensitive flow cytometry assays) and high-count MBL (clinical MBL, median B-cell
      count: 2.9 * 109/L, typically identified during the workup of low-level
      lymphocytosis). Low-count MBL has an exceedingly small risk of progression to
      CLL, and these patients do not require any specific follow-up. In contrast,
      patients with high-count MBL have a 1% to 2% per year risk of progression to CLL
      requiring therapy, as well as a higher risk of infectious complications and
      secondary malignancies. Although the overall survival of high-count MBL patients
      collectively is similar to the age- and sex-matched general population, 5-year
      survival for high-count MBL with higher-risk biologic parameters appears to be
      slightly lower than that of the general population. This review summarizes key
      concepts in the classification, diagnosis, and biology of CLL-like MBL and
      addresses several important issues in clinical management.

PMID- 24896541
TI  - Pharmacotherapy in the treatment of patients with borderline personality
      disorder: results of a survey among psychiatrists in private practices.
AB  - Pharmacotherapy still seems to play a major role in the treatment of patients
      suffering from borderline personality disorder (BPD). However, little is known
      about psychiatrists' detailed perspective on indication and significance of
      medication. A total of 233 psychiatrists in the city of Munich and in Upper
      Bavaria were asked by questionnaire about their treatment habits in the medical
      treatment of patients with BPD. One hundred and forty-one psychiatrists answered
      the questionnaire (60.5%). In total, 94% of BPD patients were treated with
      psychotropic medication. Psychiatrists predominantly saw an indication to
      prescribe antidepressants (98%), followed by antipsychotics, mood stabilizers,
      and benzodiazepines. Citalopram/escitalopram and quetiapine were mentioned most
      frequently. The results are discussed in conjunction with the international
      guidelines for the treatment of BPD. 

PMID- 24896546
TI  - Subtyping of triple-negative breast cancer.

PMID- 24896547
TI  - Update on ibrutinib.

PMID- 24896548
TI  - Sickle cell disease: new treatments and their rationale.

PMID- 24896549
TI  - Multiple myeloma: treatment updates.

PMID- 24896550
TI  - A summer of change in hematologic malignancies: highlights in B-Cell malignancies
      from the 2013 ASCO, EHA, and ICML meetings.

PMID- 24896554
TI  - Steam induced structural changes of a poly(ethylenimine) impregnated gamma
      alumina sorbent for CO2 extraction from ambient air.
AB  - Poly(ethylenimine) (PEI) impregnated mesoporous gamma-alumina sorbents are
      utilized for CO2 adsorption from dry and humid simulated ambient air, and the
      sorbents are regenerated under an environment of flowing steam for times ranging
      from 5 min to 24 h of continuous exposure. The sorbents are compared on the basis
      of equilibrium CO2 capacities from simulated air at 400 ppm of CO2, 50% relative
      humidity, and 30  degrees C as well as their physiochemical characterization by
      means of X-ray diffraction (XRD), (27)Al NMR spectroscopy, IR spectroscopy, Raman
      spectroscopy, N2 physisorption, and elemental analysis. The sorbents retain
      better than 90% of the initial equilibrium capacity of ~1.7 mmol/g at steam
      exposure times up to 12 h; however, PEI leaching reduced the capacity of the
      sorbent to 0.66 mmol/g after 24 h of continuous treatment. It is demonstrated
      that the gamma-alumina support partially hydrates to form a boehmite crystal
      phase at steam times of 90 min and longer but that this phase transition occurs
      predominately between 90 min and 12 h of steam treatment, slowing at longer times
      of 12 and 24 h of treatment. Evidence is presented to suggest that the presence
      of boehmite on the sorbent surface does not significantly alter the amine
      efficiency of impregnated PEI. The collected results suggest that gamma
      alumina/PEI composite materials are promising sorbents for CO2 capture from
      ambient air with regeneration in flowing steam. 

PMID- 24896555
TI  - Foreword.

PMID- 24896556
TI  - Environmental sustainability in the intensive care unit: challenges and
      solutions.
AB  - In acute care practice sites, the intensive care unit (ICU) is one of the most
      resource-intense environments. Replete with energy-intensive equipment,
      significant waste production, and multiple toxic chemicals, ICUs contribute to
      environmental harm and may inadvertently have a negative impact on the health of
      patients, staff, and visitors. This article evaluates the ICU on four areas of
      environmental sustainability: energy, waste, toxic chemicals, and healing
      environment and provides concrete actions ICU nurses can take to decrease
      environmental health risks in the ICU. Case studies of nurses making changes
      within their hospital practice are also highlighted, as well as resources for
      nurses starting to make changes at their health care institutions. 

PMID- 24896557
TI  - Adapt or perish--a relentless fight for survival: designing superbugs out of the
      intensive care unit.
AB  - Lethal microorganisms have terrorized man since the beginning of time, killing
      more human beings than anything else in history. The most infamous epidemic, the
      Black Death, wiped out almost half the population of Europe. To quote H.G. Wells,
      "adapt or perish, now as ever, is nature's inexorable imperative." Superbugs are
      nature's revenge on humans for their ingenuity. For decades antibiotics, which
      work by honing in on particular bacteria, have been the chief line of defense
      against infection. There is growing urgency for the judicious assessment of both
      conventional and innovative strategies with regard to antibiotic use, infection
      control, molecular detection of pathogens and adequate treatment of multidrug
      resistant organisms in hospitals, especially critical care units. Financial
      restraints, changing demographics, an aging population and the limited
      introduction of new antibiotics have established an imperative for utilization of
      goal directed strategies in infection prevention and control. Research and
      development of both clinical and environmental weapons to combat these
      adversaries is essential if man is to adapt, not perish, in this fight for
      survival. This article will provide a snapshot of advances in infection
      prevention and control, including evidence based design, as they relate to the
      critical care environment. 

PMID- 24896558
TI  - Point-of-care technology: integration for improved delivery of care.
AB  - The growing complexity of technology, equipment, and devices involved in patient
      care delivery can be staggering and overwhelming. Technology is intended to be a
      tool to help clinicians, but it can also be a frustrating hindrance if not
      thoughtfully planned and strategically aligned. Critical care nurses are key
      partners in the collaborations needed to improve safety and quality through
      health information technology (IT). Nurses must advocate for systems that are
      interoperable and adapted to the context of care experiences. The involvement and
      collaboration between clinicians, information technology specialists, biomedical
      engineers, and vendors has never been more relevant and applicable. Working
      together strategically with a shared vision can effectively provide a seamless
      clinical workflow, maximize technology investments, and ultimately improve
      patient care delivery and outcomes. Developing a strategic integrated clinical
      and IT roadmap is a critical component of today's health care environment. How
      can technology strategy be aligned from the executive suite to the bedside
      caregiver? What is the model for using clinical workflows to drive technology
      adoption? How can the voice of the critical care nurse strengthen this process?
      How can success be assured from the initial assessment and selection of
      technology to a sustainable support model? What is the vendor's role as a
      strategic partner and "co-caregiver"? 

PMID- 24896559
TI  - Let there be light and darkness: findings from a prestudy concerning cycled light
      in the intensive care unit environment.
AB  - The present study reports findings concerning light in an intensive care unit
      setting presented from 3 aspects, giving a wide view. The first part is a
      systematic review of intervention studies concerning cycled light compared with
      dim light/noncycled light. The findings showed that cycled light may be
      beneficial to preterm infant health. Second, a lighting intervention in the
      intensive care unit is presented, comparing and assessing experience of this
      lighting environment with that of an ordinary room. Significant differences were
      shown in hedonic tone, favoring the intervention environment. In the third part,
      measured illuminance, luminance, and irradiance values achieved in the lighting
      intervention room and ordinary room lighting are reported. 

PMID- 24896560
TI  - Physical design correlates of efficiency and safety in emergency departments: a
      qualitative examination.
AB  - The objective of this study was to explore and identify physical design
      correlates of safety and efficiency in emergency department (ED) operations. This
      study adopted an exploratory, multimeasure approach to (1) examine the
      interactions between ED operations and physical design at 4 sites and (2)
      identify domains of physical design decision-making that potentially influence
      efficiency and safety. Multidisciplinary gaming and semistructured interviews
      were conducted with stakeholders at each site. Study data suggest that 16 domains
      of physical design decisions influence safety, efficiency, or both. These include
      (1) entrance and patient waiting, (2) traffic management, (3) subwaiting or
      internal waiting areas, (4) triage, (5) examination/treatment area configuration,
      (6) examination/treatment area centralization versus decentralization, (7)
      examination/treatment room standardization, (8) adequate space, (9) nurse work
      space, (10) physician work space, (11) adjacencies and access, (12) equipment
      room, (13) psych room, (14) staff de-stressing room, (15) hallway width, and (16)
      results waiting area. Safety and efficiency from a physical environment
      perspective in ED design are mutually reinforcing concepts--enhancing efficiency
      bears positive implications for safety. Furthermore, safety and security emerged
      as correlated concepts, with security issues bearing implications for safety,
      thereby suggesting important associations between safety, security, and
      efficiency.

PMID- 24896561
TI  - Developing nurse and physician questionnaires to assess primary work areas in
      intensive care units.
AB  - The objective of the study was to develop instruments for describing and
      assessing some aspects of design of the primary work areas of nurses and
      physicians in intensive care units (ICUs). Separate questionnaires for ICU
      physicians and nurses were developed. Items related to individual- and unit-level
      design features of the primary work areas of nurses and physicians were organized
      using constructs found in the literature. Items related to staff satisfaction and
      staff use of time in relation to primary work area design were also included. All
      items and constructs were reviewed by experts for content validity and were
      modified as needed before use. The final questionnaires were administered to a
      convenience sample of 4 ICUs in 2 large urban hospitals. A total of 55 nurses and
      29 physicians completed the survey. The Cronbach alpha was used to measure
      internal consistency, and factor analysis was used to provide construct-related
      validity. Convergent and discriminant validity were assessed through examining
      bivariate correlations between relevant scales/items. Analysis of variance was
      used to identify whether the between-group member responses were significant
      among the 4 units. The Cronbach alpha values for all except 3 preliminary scales
      indicated acceptable reliability. Factor analysis indicated that some preliminary
      scales could be partitioned into subscales for finer descriptions of the primary
      work areas. Correlational analysis provided strong evidence of convergent and
      discriminant validity of all the scales and subscales. The significance level of
      F-statistics showed that the units were significantly different from each other,
      providing evidence of more between-unit variance than within-unit variance.
      Therefore, the questionnaires developed in the study offer a promising departure
      point for rigorous description and evaluation of the primary work areas in
      relation to staff satisfaction and use of time in ICUs at a time when the
      importance of such studies is growing. 

PMID- 24896562
TI  - Rising to the challenge: transforming an adult ICU into an adult and pediatric
      ICU.
AB  - Published literature on natural disasters describes lessons learned in preparing
      for disasters, evacuating patients, and caring for patients in the immediate
      aftermath. Some disasters, however, require longer-term solutions to best meet
      the health needs of the community during the recovery from the disaster. This
      article presents an account of one academic medical center's experience in
      transforming an existing adult burn intensive care unit into an adult and
      pediatric burn intensive care unit to meet the needs of a community following a
      hurricane. The process of training 2 groups of specialty nurses and the success
      of expanding an adult unit are described. 

PMID- 24896564
TI  - Structure of the BTB domain of Keap1 and its interaction with the triterpenoid
      antagonist CDDO.
AB  - The protein Keap1 is central to the regulation of the Nrf2-mediated
      cytoprotective response, and is increasingly recognized as an important target
      for therapeutic intervention in a range of diseases involving excessive oxidative
      stress and inflammation. The BTB domain of Keap1 plays key roles in sensing
      environmental electrophiles and in mediating interactions with the Cul3/Rbx1 E3
      ubiquitin ligase system, and is believed to be the target for several small
      molecule covalent activators of the Nrf2 pathway. However, despite structural
      information being available for several BTB domains from related proteins, there
      have been no reported crystal structures of Keap1 BTB, and this has precluded a
      detailed understanding of its mechanism of action and interaction with
      antagonists. We report here the first structure of the BTB domain of Keap1, which
      is thought to contain the key cysteine residue responsible for interaction with
      electrophiles, as well as structures of the covalent complex with the antagonist
      CDDO/bardoxolone, and of the constitutively inactive C151W BTB mutant. In
      addition to providing the first structural confirmation of antagonist binding to
      Keap1 BTB, we also present biochemical evidence that adduction of Cys 151 by CDDO
      is capable of inhibiting the binding of Cul3 to Keap1, and discuss how this class
      of compound might exert Nrf2 activation through disruption of the BTB-Cul3
      interface. 

PMID- 24896565
TI  - The cross-talk between canonical and non-canonical Wnt-dependent pathways
      regulates P-glycoprotein expression in human blood-brain barrier cells.
AB  - In this work, we investigate if and how transducers of the 'canonical' Wnt
      pathway, i.e., Wnt/glycogen synthase kinase 3 (GSK3)/beta-catenin, and
      transducers of the 'non-canonical' Wnt pathway, i.e., Wnt/RhoA/RhoA kinase
      (RhoAK), cooperate to control the expression of P-glycoprotein (Pgp) in blood
      brain barrier (BBB) cells. By analyzing human primary brain microvascular
      endothelial cells constitutively activated for RhoA, silenced for RhoA or treated
      with the RhoAK inhibitor Y27632, we found that RhoAK phosphorylated and activated
      the protein tyrosine phosphatase 1B (PTP1B), which dephosphorylated tyrosine 216
      of GSK3, decreasing the GSK3-mediated inhibition of beta-catenin. By contrast,
      the inhibition of RhoA/RhoAK axis prevented the activation of PTP1B, enhanced the
      GSK3-induced phosphorylation and ubiquitination of beta-catenin, and reduced the
      beta-catenin-driven transcription of Pgp. The RhoAK inhibition increased the
      delivery of Pgp substrates like doxorubicin across the BBB and improved the
      doxorubicin efficacy against glioblastoma cells co-cultured under a BBB
      monolayer. Our data demonstrate that in human BBB cells the expression of Pgp is
      controlled by a cross-talk between canonical and non-canonical Wnt pathways. The
      disruption of this cross-talk, e.g., by inhibiting RhoAK, downregulates Pgp and
      increases the delivery of Pgp substrates across the BBB. 

PMID- 24896568
TI  - Frizzled fissure to improve central nervous system drug delivery?
AB  - Delivery of therapeutics to the brain is challenging because of efflux pumps
      located in the vascular endothelium. A detailed analysis of Wnt signaling in a
      human brain endothelial cell line indicates that expression and function of P
      glycoprotein, a major efflux transporter, is controlled by non-canonical Wnt
      signaling. Inhibition of this pathway leads to downregulation of P-glycoprotein
      and increased transcellular drug transport and reveals a potential strategy for
      improving drug delivery for treatment of neurologic diseases. 

PMID- 24896570
TI  - From the editor.

PMID- 24896566
TI  - Plasmin-dependent modulation of the blood-brain barrier: a major consideration
      during tPA-induced thrombolysis?
AB  - Plasmin, the principal downstream product of tissue-type plasminogen activator
      (tPA), is known for its potent fibrin-degrading capacity but is also recognized
      for many non-fibrinolytic activities. Curiously, plasmin has not been
      conclusively linked to blood-brain barrier (BBB) disruption during recombinant
      tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the
      substantial involvement of tPA in the modulation of BBB permeability and the co
      existence of tPA and plasminogen in both blood and brain throughout the ischemic
      event. Here, we review the work that argues a role for plasmin together with
      endogenous tPA or rtPA in BBB alteration, presenting the overall controversy
      around the topic yet creating a rational case for an involvement of plasmin in
      this process. 

PMID- 24896571
TI  - Guest editorial.

PMID- 24896569
TI  - Effects of angiopoietin-1 on hemorrhagic transformation and cerebral edema after
      tissue plasminogen activator treatment for ischemic stroke in rats.
AB  - An angiogenesis factor, angiopoietin-1 (Ang1), is associated with the blood-brain
      barrier (BBB) disruption after focal cerebral ischemia. However, whether
      hemorrhagic transformation and cerebral edema after tissue plasminogen activator
      (tPA) treatment are related to the decrease in Ang1 expression in the BBB remains
      unknown. We hypothesized that administering Ang1 might attenuate hemorrhagic
      transformation and cerebral edema after tPA treatment by stabilizing blood
      vessels and inhibiting hyperpermeability. Sprague-Dawley rats subjected to
      thromboembolic focal cerebral ischemia were assigned to a permanent ischemia
      group (permanent middle cerebral artery occlusion; PMCAO) and groups treated with
      tPA at 1 h or 4 h after ischemia. Endogenous Ang1 expression was observed in
      pericytes, astrocytes, and neuronal cells. Western blot analyses revealed that
      Ang1 expression levels on the ischemic side of the cerebral cortex were decreased
      in the tPA-1h, tPA-4h, and PMCAO groups as compared to those in the control group
      (P = 0.014, 0.003, and 0.014, respectively). Ang1-positive vessel densities in
      the tPA-4h and PMCAO groups were less than that in the control group (p = 0.002
      and <0.001, respectively) as well as that in the tPA-1h group (p = 0.047 and
      0.005, respectively). These results suggest that Ang1-positive vessel density was
      maintained when tPA was administered within the therapeutic time window (1 h),
      while it was decreased when tPA treatment was given after the therapeutic time
      window (4 h). Administering Ang1 fused with cartilage oligomeric protein (COMP)
      to supplement this decrease has the potential to suppress hemorrhagic
      transformation as measured by hemoglobin content in a whole cerebral homogenate
      (p = 0.007) and cerebral edema due to BBB damage (p = 0.038), as compared to
      administering COMP protein alone. In conclusion, Ang1 might be a promising target
      molecule for developing vasoprotective therapies for controlling hemorrhagic
      transformation and cerebral edema after tPA treatment.

PMID- 24896572
TI  - Teamwork in health care.
AB  - It is becoming increasingly clear that maintaining and improving the health of
      the population, and doing so in a financially sustainable manner, requires the
      coordination of acute medical care with long-term care, and social support
      services, that is, team-based care. Despite a growing body of evidence on the
      benefits of team-based care, the health care ecosystem remains "resistant" to a
      broader implementation of such care models. This resistance is a function of both
      system-wide and organizational barriers, which result primarily from
      fragmentation in reimbursement for health care services, regulatory restrictions,
      and the siloed nature of health professional education. To promote the broader
      adoption of team-based care models, the health care system must transition to pay
      for value reimbursement, as well as break down the educational silos and move
      toward team-based and value-based education of health professionals.

PMID- 24896573
TI  - It takes a team: creating a hematology/hematopoietic cell therapy day hospital.
AB  - It is anticipated that by the year 2020, the United States will double the number
      of hematopoietic cell therapy transplants completed in this country. As a
      freestanding cancer hospital with one of the largest hematopoietic cell therapy
      transplant programs in the country, City of Hope embarked on an innovative
      strategy to address current capacity issues and prospectively plan for future
      expansion of transplant volumes. This article describes the planning process that
      was undertaken using various content-specific focused teams to address all
      components of designing and opening an outpatient day hospital suitable for
      management of patients undergoing transplant in an ambulatory setting. The
      deliverables of the 11 teams that drove this planning process are addressed.

PMID- 24896567
TI  - Highly energized inhibitory interneurons are a central element for information
      processing in cortical networks.
AB  - Gamma oscillations (~30 to 100 Hz) provide a fundamental mechanism of information
      processing during sensory perception, motor behavior, and memory formation by
      coordination of neuronal activity in networks of the hippocampus and neocortex.
      We review the cellular mechanisms of gamma oscillations about the underlying
      neuroenergetics, i.e., high oxygen consumption rate and exquisite sensitivity to
      metabolic stress during hypoxia or poisoning of mitochondrial oxidative
      phosphorylation. Gamma oscillations emerge from the precise synaptic interactions
      of excitatory pyramidal cells and inhibitory GABAergic interneurons. In
      particular, specialized interneurons such as parvalbumin-positive basket cells
      generate action potentials at high frequency ('fast-spiking') and synchronize the
      activity of numerous pyramidal cells by rhythmic inhibition ('clockwork'). As
      prerequisites, fast-spiking interneurons have unique electrophysiological
      properties and particularly high energy utilization, which is reflected in the
      ultrastructure by enrichment with mitochondria and cytochrome c oxidase, most
      likely needed for extensive membrane ion transport and gamma-aminobutyric acid
      metabolism. This supports the hypothesis that highly energized fast-spiking
      interneurons are a central element for cortical information processing and may be
      critical for cognitive decline when energy supply becomes limited ('interneuron
      energy hypothesis'). As a clinical perspective, we discuss the functional
      consequences of metabolic and oxidative stress in fast-spiking interneurons in
      aging, ischemia, Alzheimer's disease, and schizophrenia. 

PMID- 24896574
TI  - Interprofessional teams in the patient-centered medical home.
AB  - The implementation of patient-centered medical homes has reinforced the need for
      interprofessional practice as the means to increasing patient quality. The nurse
      executive is well positioned to facilitate interprofessional collaborative
      practice; however, more sophisticated and focused strategies are needed for high
      levels of interprofessional partnerships that wholeheartedly ensure patient
      driven health care. This article presents strategies to meet the needs of the
      patient as the interprofessional team coordinates activities across the
      continuum. Strategies include having a clear understanding of the patient
      centered medical homes concept, clear articulation of patient centricity
      behaviors, selection of metrics that are actionable, competence in developing
      high-functioning partnerships, and processes to strengthen the organizational
      cultural to support interprofessional practice.

PMID- 24896575
TI  - Teamwork: an essential for leading and launching innovation.
AB  - Teamwork and innovation require a merging of special skills sets to produce the
      best outcomes. Collaboration and innovation have become core competencies for
      effectiveness in every industry. The capacity to collaborate and innovate has
      never been more important, especially in health care, with the regulatory and
      quality mandates to evaluate every aspect of service to ensure that we add value
      for patients and families. The examination of teamwork and innovation, which are
      inextricably linked, are described and discussed. The art of building teams,
      steps for leading change, and an approach to innovation in health care are
      described. The University of Texas Medical Branch in Galveston, Texas, shares one
      approach and experience called Innovation Forerunners-nurses from all levels and
      areas-to embed the tools and concepts of teamwork and innovation across patient
      care areas.

PMID- 24896577
TI  - Building a team through a strategic planning process.
AB  - Strategic planning is a process often left to senior hospital leadership, with
      limited input from unit-level, bedside patient care providers. This frequent
      approach to strategic planning misses the opportunity to engage a wide range of
      employees, build a shared sense of commitment, produce a collaborative team
      environment, and to generate greater acceptance of the plan. The Patient Care
      Services division at the University of Chicago Medicine used a strategic planning
      process that incorporated 360-degree input from both within the Patient Care
      Services division and outside of the division. The result is a strategic vision
      and plan that, shaped by broad-based input from both internal and external
      constituencies, is strengthened by the team that emerged from the process.
      Through the process of identifying a common understanding of the group's future
      direction, a shared purpose was created that transcended traditional professional
      boundaries and shaped a cohesive team focused on effective and efficient patient
      care. Now, with a focused strategic plan and a team centered on a shared purpose,
      the team is beginning to effectively deliver on the plan.

PMID- 24896576
TI  - Seven behaviors to advance teamwork: findings from a study of innovation
      leadership in a simulation center.
AB  - Traditional notions of individual-based leadership behaviors are no longer
      adequate to achieve innovation in health care organizations. A major contributing
      factor for limited innovation is that outdated leadership practices, such as
      leader centricity, linear thinking, and poor readiness for innovation, are being
      used in health care organizations. Through a qualitative case study analysis of
      innovation implementation, 7 characteristics of innovation leadership, founded in
      team behaviors, were uncovered. The characteristics that were uncovered included
      boundary spanning, risk taking, visioning, leveraging opportunity, adaptation,
      coordination of information flow, and facilitation. These characteristics
      describe how leaders throughout the system were able to influence and implement
      innovation successfully.

PMID- 24896578
TI  - Communication that builds teams: assessing a nursing conflict intervention.
AB  - Quality communication is essential for building strong nursing teams.
      Structurational divergence (SD) theory explains how institutional factors can
      result in poor communication and conflict cycles; the theory has been developed
      in nursing context, although it is applicable to all organizational settings. We
      describe the design, implementation, and evaluation of an intervention to reduce
      SD and improve nurses' work life and team-member relationships. An intensive 9
      hour course provided training in conflict/SD analysis and dialogic conflict/SD
      management to 36 working nurses from a variety of settings. Quantitative pre- and
      posttests were administered, with a comparison sample. The course reduced
      measures of negative conflict attitudes and behaviors: direct personalization,
      persecution feelings, negative relational effects, ambiguity intolerance, and
      triangulation (gossiping and complaining to uninvolved third parties). The course
      also increased important attitudes necessary for productive dialogue and conflict
      management: perceptions of positive relational effects, conflict liking, and
      positive beliefs about arguing. As compared with nonparticipants, participant
      posttests showed lower conflict persecution; higher recognition of positive
      relational effects; lower perceptions of negative relational effects; higher
      conflict liking; lower ambiguity intolerance; and lower tendency to triangulate.
      Qualitatively, participants perceived better understanding of, and felt more
      empowered to manage, workplace conflicts and to sustain healthier workplace
      relationships. This intervention can help nurses develop tools to improve system
      level function and build productive team relationships.

PMID- 24896579
TI  - Profile of an excellent nurse manager: identifying and developing health care
      team leaders.
AB  - The purpose of this research was to identify the profile of an excellent nurse
      manager who can lead effective health care teams. Leadership attributes and
      competencies that characterize an excellent nurse manager and tools to identify
      them are lacking in the literature but are required to efficiently and
      effectively address the growing shortage of registered nurses (RNs) in health
      care team leadership roles and the critical linkage of these roles to patient
      outcomes. A profile of an excellent nurse manager was developed on the basis of
      the responses of nurse managers across the United States who had been identified
      as excellent or competent by chief nurse executive assessment or/and the Nurse
      Manager Ability, Leadership, and Support of Nurses staff survey to the Kouzes and
      Posner Leadership Practices Inventory: Self Instrument. Statistically significant
      distinctions exist between nurse managers who are excellent and those who are
      competent as assessed by the Five Practices of Exemplary Leadership, which
      together comprise the profile of an excellent nurse manager. The Kouzes and
      Posner Leadership Practices Inventory: Self Instrument can be used to identify,
      recruit, and develop RNs in the nurse manager role as excellent leaders of
      effective health care teams.

PMID- 24896580
TI  - Embracing the tools of technology.

PMID- 24896581
TI  - The 2010 Institute of Medicine report and the 2008 consensus document outcomes:
      implications for the chief nursing officer--part 1.

PMID- 24896583
TI  - Effect of exercise programs with aerobic exercise sessions of similar intensity
      but different frequency and duration on health-related measures in overweight
      women.
AB  - BACKGROUND: This study investigated health-related effects of exercise programs
      with exercise sessions of similar intensity but different frequency and duration.
      METHODS: Thirty-four overweight women were randomized into either long-bout (LB)
      or short-bout (SB) exercise groups. Participants performed an 8-week supervised
      program, with the LB group exercising for 75 minutes twice per week, and the SB
      group for 30 minutes on 5 days of the week. RESULTS: The LB group completed 16
      sessions at a heart rate (HR) of 127 +/- 1 beat.min-1 and the SB group completed
      40 sessions at a HR of 126 +/- 1 beat.min-1. Weekly energy expenditure of
      exercise was not different between groups (LB group, 5.64 +/- 0.34 MJ; SB group,
      5.83 +/- 0.23 MJ). Training significantly (P < .05) increased measures of
      cardiorespiratory fitness, decreased waist circumference, insulin resistance, and
      diastolic blood pressure. The group * time interaction was not significant for
      any of these factors, indicating that responses to exercise training did not
      differ between the SB and LB groups. CONCLUSIONS: Health-related outcomes of
      exercise programs with similar energy expenditure are independent of frequency
      and duration of exercise sessions. This provides individuals with a degree of
      flexibility in exercise program planning.

PMID- 24896585
TI  - Single core-shell nanoparticle probes for non-invasive magnetic force microscopy.
AB  - We present an easy, fast and reliable method for the preparation of magnetic
      force microscopy (MFM) probes based on single Co nanoparticles (NPs). Due to
      their dipolar character, these magnetic probes open up a new approach for
      quantitative and non-invasive MFM measurements on the nanometer length scale. To
      guarantee long-term stability of these tips under ambient conditions, an
      ultrathin protecting Au shell was grown around the Co NPs through photochemical
      deposition. Single magnetic particles were firmly attached to standard silicon
      AFM tips using bifunctional self-assembling molecules. Such probes were tested on
      longitudinal magnetic recording media and compared to the results as recorded
      with conventional thin-film MFM tips. Easy data interpretation of the magnetic
      nanoparticle probes in a point dipole model is shown. Our nanoparticle tips
      provide excellent endurance for MFM recording, enable non-invasive probing while
      maintaining a high sensitivity, resolution, and reproducibility. 

PMID- 24896582
TI  - Children who received PCV-10 vaccine from a two-dose vial without preservative
      are not more likely to develop injection site abscess compared with those who
      received pentavalent (DPT-HepB-Hib) vaccine: a longitudinal multi-site study.
AB  - BACKGROUND: The single dose pneumonia ten-valent vaccine has been widely used and
      is highly efficacious against selected strains Streptococcus pneumonia. A two
      dose vial without preservative is being introduced in developing countries to
      reduce the cost of the vaccine. In routine settings improper immunization
      practice could result in microbial contamination leading to adverse events
      following immunization. OBJECTIVE: To monitor adverse events following
      immunization recommended for routine administration during infancy by comparing
      the rate of injection-site abscess between children who received PCV-10 vaccine
      and children who received the Pentavalent (DPT-HepB-Hib) vaccine. METHODS: A
      longitudinal population-based multi-site observational study was conducted
      between September 2011 and October 2012. The study was conducted in four existing
      Health and Demographic Surveillance sites run by public universities of
      Abraminch, Haramaya, Gondar and Mekelle. Adverse events following Immunization
      were monitored by trained data collectors. Children were identified at the time
      of vaccination and followed at home at 48 hour and 7 day following immunization.
      Incidence of abscess and relative risk with the corresponding 95% Confidence
      Intervals were calculated to examine the risk difference in the comparison
      groups. RESULTS: A total of 55, 268 PCV and 37, 480 Pentavalent (DPT-HepB-Hib)
      vaccinations were observed. A total of 19 adverse events following immunization,
      10 abscesses and 9 deaths, were observed during the one year study period. The
      risk of developing abscess was not statistically different between children who
      received PCV-10 vaccine and those received Pentavalent (RR = 2.7, 95% CI 0.576
      12.770), and between children who received the first aliquot of PCV and those
      received the second aliquot of PCV (RR = 1.72, 95% CI 0.485-6.091). CONCLUSION:
      No significant increase in the risk of injection site abscess was observed
      between the injection sites of PCV-10 vaccine from a two-dose vial without
      preservative and pentavalent (DPT-HepB-Hib) vaccine in the first 7 days following
      vaccination.

PMID- 24896586
TI  - Intimate partner violence among undergraduate students of two universities of the
      state of Sao Paulo, Brazil.
AB  - INTRODUCTION: The prevalence of violence in intimate relationships, suffered or
      perpetrated, was estimated among undergraduate students, be it physical,
      psychological and sexual, describing the overlap between them. This is an
      original study and there is scarce literature on this matter in Brazil. Men and
      women were investigated and some issues on gender violence were discussed.
      METHODS: The study is part of the multicenter survey "International Study of
      Violence in Dating - IDVS" conducted in 2002 - 2003, using its standardized
      instrument. A total of 362 students, from two universities in the state of Sao
      Paulo, one public and one private, answered the self-reported questionnaire,
      being 37% male and 63% female, mean age of 20 years old. Suffered and perpetrated
      intimate partner violence during life was examined. RESULTS: Among all
      interviewees, 75.9% suffered and 76.4% perpetrated some kind of violence
      throughout life. Psychological violence was the most prevalent type, followed by
      sexual violence, both suffered and perpetrated. The great superposition between
      suffered and perpetrated violence (83.9%) reflects the reciprocity of aggression,
      with no observed difference between men and women. The results of this study are
      consistent with previous literature on dating violence, which shows high
      prevalence of suffered and perpetrated violence, besides reciprocity for both men
      and women. CONCLUSIONS: Intervention actions at this stage of intimate
      relationships may potentially impact on subsequent marital partnership
      situations.

PMID- 24896584
TI  - Functional analysis of the Drosophila embryonic germ cell transcriptome by RNA
      interference.
AB  - In Drosophila melanogaster, primordial germ cells are specified at the posterior
      pole of the very early embryo. This process is regulated by the posterior
      localized germ plasm that contains a large number of RNAs of maternal origin.
      Transcription in the primordial germ cells is actively down-regulated until germ
      cell fate is established. Bulk expression of the zygotic genes commences
      concomitantly with the degradation of the maternal transcripts. Thus, during
      embryogenesis, maternally provided and zygotically transcribed mRNAs determine
      germ cell development collectively. In an effort to identify novel genes involved
      in the regulation of germ cell behavior, we carried out a large-scale RNAi screen
      targeting both maternal and zygotic components of the embryonic germ line
      transcriptome. We identified 48 genes necessary for distinct stages in germ cell
      development. We found pebble and fascetto to be essential for germ cell migration
      and germ cell division, respectively. Our data uncover a previously unanticipated
      role of mei-P26 in maintenance of embryonic germ cell fate. We also performed
      systematic co-RNAi experiments, through which we found a low rate of functional
      redundancy among homologous gene pairs. As our data indicate a high degree of
      evolutionary conservation in genetic regulation of germ cell development, they
      are likely to provide valuable insights into the biology of the germ line in
      general. 

PMID- 24896587
TI  - Sexual abuse and alcohol use among women in metropolitan Sao Paulo, Brazil: a
      general population study.
AB  - OBJECTIVE: The present study aimed at estimating the prevalence of lifetime
      sexual abuse among women and at investigating its association with alcohol
      consumption. METHOD: Population-based survey conducted through a representative
      and stratified cluster sample of metropolitan Sao Paulo. GENACIS questionnaire
      was used. Sample unit was the home, and all residents aged 18 years and over were
      interviewed. The outcome was lifetime sexual abuse. The univariate statistical
      analysis used the Rao-Scott test. Logistic regression was used for the
      multivariate analysis. RESULTS: The final sample totalized 1,216 women aged 18
      years and over; the response rate was 75.0%. Most women were married (56.6%) and
      had less than 12 years of formal education (59.0%); 46.2% were aged between 25
      and 44 years, and 44.4% had a low income. Of the respondents, 7.5% reported
      having suffered lifetime sexual abuse. Multiple logistic regression model showed
      an association between lifetime sexual abuse and being a heavy drinker (OR =
      4.97) and being a former drinker (OR = 2.04). CONCLUSIONS: There are few
      population studies in Brazil investigating sexual abuse and its relation to
      alcohol use. Although the prevalence of lifetime sexual abuse in the present
      study was smaller than that observed in other studies, it is a highly expressive
      percentage on account of its social and economic impact, as well as its potential
      effect on the health system.

PMID- 24896588
TI  - Infant mortality in Cabinda, Angola: challenge to health public policies.
AB  - OBJECTIVE: To critically discuss, describe and analyze the data on infant
      mortality provided by public health services of Cabinda, Angola. METHOD: The
      deaths of children aged less than one year old in 2007 and 2008 were analyzed in
      the Cabinda province. Provincial hospital records and those of the WHO office
      were used due to the limited quality and availability of official information.
      RESULTS: In 2007, 11,734 children were born, and 366 of them died in their first
      year of life: 113 on the first day, 87 by the 28th day and 166 in the remaining
      337 days. In 2008, 13,441 children were born and 275 died; 109 died on the first
      day and 69 by the 28th day. Malaria was the main cause of death (one out of
      three). Pneumonia was the second cause in 2007 and the third in 2008, presenting
      consistent reduction, from 65 to 40 deaths. Cases of diarrhea from 2007 (9.83%)
      decreased to 3.27% in 2008. Tetanus accounted for about 5% of all deaths.
      Perinatal causes increased in proportion, particularly neonatal asphyxia (17.75%
      in 2007 and 26.90% in 2008) and prematurity (13.38% in 2007 and 17.45% in 2008).
      CONCLUSIONS: Improvements in the quality of prenatal care, attendance during
      delivery and to new born risk, would reduce infant mortality. The lack of
      sanitation, inadequate water supply and poor access to health services played an
      important role as determinants of infant mortality observed in Cabinda. This
      study highlights the need to reorganize the civil registration system.

PMID- 24896589
TI  - Mortality due to diseases of the circulatory system among the elderly population
      in Brazilian Amazon: temporal and spatial analysis.
AB  - INTRODUCTION: Circulatory Diseases (CD) are the major cause of death among the
      elderly population in Brazilian Amazon. OBJECTIVE: to analyze standardized
      mortality rates of diseases of the circulatory system (DCS), according to the
      main causes of death among the elderly, in microregions of the Brazilian Amazon,
      in the period of 1998 - 2007. METHODS: ecological study of mortality rates
      distribution standardized by CD and corrected by deaths from poorly defined
      causes among the elderly (> 65 years of age) who lived in Brazilian Amazon in the
      period of 1998 - 2007. The analysis were carried out by the linear regression,
      trend, and spatial distribution of Kernel. RESULTS: We verified an increasing
      trend in mortality by CD (beta1 = 28.34 p = 0.01), due to the increasing trend in
      the States of Maranhao and Tocantins. The central region of Mato Grosso, Northern
      Tocantins, Eastern Para and Southwestern Maranhao present hot spots with the
      highest mortality rates. Males present higher rates when compared to females all
      over the region; rates of mortality due to acute myocardial infarction and
      hypertensive disease present the same spatial standard of the CD group and the
      rates of cerebrovascular diseases present a different spatial distribution
      standard. Increment in mortality rates according to age was observed: the greater
      the age, the higher is mortality by CD. CONCLUSION: The Brazilian Amazon presents
      an increasing trend with high rates of mortality by the circulatory diseases, and
      the geographic areas with the highest rates are around the Brazilian Amazon, in
      the states of Tocantins, Maranhao and Mato Grosso.

PMID- 24896590
TI  - Prevalence of high blood pressure in Brazilian adolescents and quality of the
      employed methodological procedures: systematic review.
AB  - OBJECTIVE: To review the literature on studies that estimated the prevalence of
      high blood pressure (HBP) or systemic arterial hypertension (SAH) in Brazilian
      adolescents, considering the employed methodological procedures. METHODS:
      Bibliographical research of prevalence studies of HBP/SAH in adolescents from
      1995 to 2010. The search was conducted in the electronic databases
      PubMed/Medline, Lilacs, SciELO, and Isi Adolec. The descriptors "hypertension",
      "BP", "teen", "students", "cross-sectional", "prevalence" and "Brazil" were used
      in Portuguese and English. Furthermore, a score ranging from 0 to 18 based on
      Recommendations for Blood Pressure Measurement in Humans and Experimental Animals
      and the VI Brazilian Guidelines of Hypertension was elaborated, in order to
      analyze the procedures used to measure BP in studies. RESULTS: Twenty-one
      articles were identified, mostly published in the last 10 years, and 90.5% were
      performed in school-based and regions of the Southeast, Northeast and South. The
      prevalence of HBP/SAH ranged from 2.5 to 30.9%. The score of the studies ranged
      from 0 to 16. A significant negative correlation (rho = -0.504; p = 0.020) was
      observed between the prevalence of HBP/SAH and the score of BP measurement
      quality. CONCLUSION: The great variability of PAE/SAH estimates appears to be
      influenced by methodological procedures used in the studies.

PMID- 24896591
TI  - Does the previous diagnosis of arterial hypertension affect one's daily life? Pro
      Saude Study.
AB  - In addition to damaging several target organs, arterial hypertension may
      negatively impact patients' activities of daily living. Biological and behavioral
      mechanisms underlying such limitations have yet to be clarified. The objectives
      of this study were to investigate whether having been previously told of a
      hypertension diagnosis is associated with the frequency and duration of temporary
      limitations in activities of daily living, and whether these relationships differ
      by gender, age, or socioeconomic position. We analyzed sectional data from 2,666
      participants (56% women; 55% with high school or lower schooling) at the baseline
      phase (1999 - 2001) of a longitudinal investigation of university employees in
      Rio de Janeiro, Brazil (Pro-Saude Study), asking participants whether they had
      ever been diagnosed with hypertension by a health professional, if they had been
      unable to perform any activities of daily living due to a health problem in the
      previous 2 weeks, and for how many days that had occurred. Multinomial logistic
      regression models were fitted for the overall study population and for age,
      gender, educational level, and per capita household income strata. Associations
      between hypertension diagnosis and temporary limitations were not observed in the
      overall study population and in gender, education and income strata. However,
      there were higher odds of temporary limitations among participants aged 55 years
      old or more with hypertension diagnosis (adjusted OR = 9.5; 95%CI 1.5 - 58.6),
      regardless of blood pressure levels and use of antihypertensive medication.
      Elderly people may keep an attitude of higher vigilance regarding conditions or
      events potentially worsening their health status. 

PMID- 24896592
TI  - Excessive daytime sleepiness in the elderly: association with cardiovascular
      risk, obesity and depression.
AB  - OBJECTIVE: To observe the relationship between Excessive Daytime Sleepiness (EDS)
      and the presence of risk factors for cardiovascular dysfunction, depression and
      obesity in the elderly. METHODS: We interviewed 168 elderly from the community of
      Campina Grande, Paraiba. They were selected according to health districts in the
      period of 2010. We used the Epworth Sleepiness Scale to diagnose excessive
      daytime sleepiness (> 10 points); waist circumference for the risk of
      cardiovascular dysfunction (> 94 or > 80 cm); Geriatric Depression Scale for
      depression (>10 points) and body mass index for obesity (> 25 kg/m2). Association
      analysis was performed by the Chi-square test adjusted for sex and age group,
      adopting alpha < 0.05. RESULTS: One hundred and sixty eight elderly individuals
      with mean age of 72.34 +/- 7.8 years old participated in this study, being 122
      (72.6%) women. EDS was identified in 53 (31.5%) of them; depression, in 72
      (42.9%); overweight/obesity, in 95 (64.46%); and risk of cardiovascular
      dysfunction, in 129 (79.6%). Depressed men (78.6%, p = 0.0005) and risk of
      cardiovascular dysfunction (57.1%, p = 0.02) were more prone to EDS. In women,
      only obesity was related to sleepiness (42.1%, p = 0.01). Only those aged between
      70 - 79 years old showed association between sleepiness and obesity. CONCLUSION:
      It was found that obesity for women, and depression and cardiovascular
      dysfunction risking for men were associated with EDS in the elderly. The variable
      sex is a confusion condition for the association with sleepiness.

PMID- 24896593
TI  - Prevalence of cognitive impairment and associated factors among the elderly in
      Bage, Rio Grande do Sul, Brazil.
AB  - It is estimated that until 2020 the elderly will represent 13% of the total
      Brazilian population, and there is increasing concern about healthy aging and low
      rates of cognitive impairment. This cross-sectional study aimed to identify the
      prevalence of cognitive impairment, using the Mini-Mental State Examination
      (MMSE) in a sample of 1,593 elderly aged 60 years old and more who were living in
      the community of the city of Bage, Southern Brazil, in 2008. The Poisson
      regression model was used for estimating crude and adjusted prevalence ratios;
      their related 95% confidence intervals and p-values lower than 0.05 were
      considered statistically significant. The prevalence of cognitive impairment was
      of 34% and statistically associated with gender (female), age (older), schooling
      (less educated), lower economic classes, without retirement, with depression and
      functional limitation. The high magnitude with increased occurrence among poor
      and vulnerable groups contributes to the implementation of public policies in
      order to improve care, prevent diseases and promote the independence and autonomy
      of the elderly population. 

PMID- 24896594
TI  - Brazilian normative data for the Short Form 36 questionnaire, version 2.
AB  - METHODS: The study Pesquisa Dimensoes Sociais das Desigualdades (PDSD) (Social
      Dimensions of Inequalities) involves 12,423 randomly selected Brazilian men and
      women aged 18 years old or more from urban and rural areas of the five Brazilian
      regions, and the information collected included the SF-36 as a measure of health
      related quality of life. This provided a unique opportunity to develop age and
      gender-adjusted normative data for the Brazilian population. RESULTS: Brazilian
      men scored substantially higher than women on all eight domains and the two
      summary component scales of the SF-36. Brazilians scored less than their
      international counterparts on almost all of SF-36 domains and both summary
      component scales, except on general health status (US), pain (UK) and vitality
      (Australia, US and Canada). CONCLUSION: The differences in the SF-36 scores
      between age groups, genders and countries confirm that these Brazilian norms are
      necessary for comparative purposes. The data will be useful for assessing the
      health status of the general population and of patient populations, and the
      effect of interventions on health-related quality of life.

PMID- 24896595
TI  - Validation of a quantitative food frequency questionnaire developed to under
      graduate students.
AB  - A validity test of a Food Frequency Questionnaire was carried out using 50
      students of health occupation in Sao Paulo, Brazil. Therefore, a three day
      dietary record was used as reference method and variables such as energy,
      macronutrients and dietary fiber were analyzed. The accordance between the Food
      Frequency Questionnaire and average data from dietary record was tested with
      kappa statistics and intra-class correlation coefficients (ICC). Limits of
      agreement were estimated by the Bland-Altman's method. Better results were found
      for calories (ICC 0.43; 95%CI 0.17 - 0.63) and non-energy-adjusted nutrients,
      except dietary fiber (ICC 0.34; 95%CI 0.07 - 0.56). The percentage of individuals
      classified in the same category of consumption was nearly half (49.8%), while
      only 16% of them were classified in opposite categories. With the exception of
      lipids, other analyzed variables tended to be overestimated by the Food Frequency
      Questionnaire. The Food Frequency Questionnaire is recommended as a method of
      assessing food intake of university students in studies which focus on calorie
      estimates and also intend to classify groups into intake categories.

PMID- 24896596
TI  - Geospatial analysis applied to epidemiological studies of dengue: a systematic
      review.
AB  - A systematic review of the geospatial analysis methods used in the dengue fever
      studies published between January 2001 and March 2011 was undertaken. In
      accordance with specific selection criteria thirty-five studies were selected for
      inclusion in the review. The aim was to assess the types of spatial methods that
      have been used to analyze dengue transmission. We found twenty-one different
      methods that had been used in dengue fever epidemiological studies in that
      period, three of which were most frequently used. The results show that few
      articles had applied spatial analysis methods in dengue fever studies; however,
      whenever they were applied they contributed to a better understanding of dengue
      fever geospatial diffusion. 

PMID- 24896597
TI  - Deaths of bicycle riders in Brazil: characteristics and trends during the period
      of 2000 - 2010.
AB  - INTRODUCTION: In Brazil, bicycle use has been increasing. Accidents involving
      cyclists are important causes of morbidity and mortality. OBJECTIVE: To describe
      the mortality of cyclists injured in transport accidents in Brazil, the
      characteristics of the victims and of the occurrence, and to investigate its
      trends during the period between 2000 and 2010. METHODS: A descriptive study with
      data from the Mortality Information System (SIM) was conducted in the period of
      2000 - 2010. Crude and age-standardized corrected mortality rates were calculated
      for Brazil, its macro-regions and states. Linear regression was used to study the
      trends. RESULTS: In the period of 2000 - 2010, 32,422 bicycle-related deaths were
      identified in Brazil. In 2010, there were, on average, 8.8 bicycle-related deaths
      per day. Age-standardized mortality rates for the country were 15.3 and 15.9
      deaths per million inhabitants in 2000 and 2010, respectively (p = 0.725). During
      the whole period, the Center-Western region showed the highest rates, though
      stable, corresponding to 23.4 deaths per million inhabitants in 2010. Men
      accounted for 85.4% of deaths, with death risk 5 times higher than women.
      CONCLUSION: In spite of the stable rates for the country, there was an increase
      trend in the Northern and Northeastern regions, while a decreasing trend was
      observed in the Southern and Southeastern regions. The risk of death was higher
      among men, elderly, and people living in large cities and at the Center-Western
      region.

PMID- 24896598
TI  - Knowledge about mammography and associated factors: population surveys with
      female adults and elderly.
AB  - The purpose of this paper is to describe the knowledge about mammography and to
      identify associated factors in female adults and elderly. Data were obtained from
      two population surveys, one with female adults and another with elderly women
      from Florianopolis (SC) in 2009 - 2010. A descriptive analysis of the variables
      was carried out, the appropriate mean of responses about mammography was
      estimated and crude and adjusted Poisson regression was conducted to identify
      associated factors. Among adults, 23.1% answered all of the questions
      appropriately and the appropriate average responses was 7.2 (95%CI 7.1 - 7.3) in
      a total of 9. In the adjusted model, older age, higher education and income were
      associated with knowledge about mammography. For the elderly, 15.3% answered all
      questions appropriately and the average of appropriate responses was 6.4 (95%CI
      5.2 - 6.5) and the factors associated with knowledge about mammography in the
      adjusted model were younger age groups, increased education and income, and
      identification of mammography as the main diagnostic method for breast cancer.
      Information about mammography can neither be transmitted in a clear way nor be
      easily understood; there are also demographic and socioeconomic differences
      concerning the knowledge about the exam. 

PMID- 24896599
TI  - Early mortality after neonatal surgery: analysis of risk factors in an optimized
      health care system for the surgical newborn.
AB  - OBJECTIVE: Anesthetic and operative interventions in neonates remain hazardous
      procedures, given the vulnerability of the patients in this pediatric population.
      The aim was to determine the preoperative and intraoperative factors associated
      with 30-day post-operative mortality and describe mortality outcomes following
      neonatal surgery under general anesthesia in our center. METHODS: Infants less
      than 28 days of age who underwent general anesthesia for surgery during an 11
      year period (2000 - 2010) in our tertiary care pediatric center were
      retrospectively identified using the pediatric intensive care unit database.
      Multiple logistic regression was used to identify independent preoperative and
      intraoperative factors associated with 30-day post-operative mortality. RESULTS:
      Of the 437 infants in the study (median gestational age at birth 37 weeks, median
      birth weight 2,760 grams), 28 (6.4%) patients died before hospital discharge. Of
      these, 22 patients died within the first post-operative month. Logistic
      regression analysis showed increased odds of 30-day post-operative mortality
      among patients who presented American Society of Anesthesiologists physical
      status (ASA) score 3 or above (odds ratio 19.268; 95%CI 2.523 - 147.132) and
      surgery for necrotizing enterocolitis/gastrointestinal perforation (OR 5.291;
      95%CI 1.962 - 14.266), compared to those who did not. CONCLUSION: The overall in
      hospital mortality of 6.4% is within the prevalence reported for developed
      countries. Establishing ASA score 3 or above and necrotizing
      enterocolitis/gastrointestinal perforation as independent risk factors for early
      mortality in neonatal surgery may help clinicians to more adequately manage this
      high risk population.

PMID- 24896600
TI  - Access to and utilization of prenatal care services in the Unified Health System
      of the city of Rio de Janeiro, Brazil.
AB  - Prenatal care consists of practices considered to be effective for the reduction
      of adverse perinatal outcomes. However, studies have demonstrated inequities in
      pregnant women's access to prenatal care, with worse outcomes among those with
      lower socioeconomic status. The objective of this study is to evaluate access to
      and utilization of prenatal services in the Sistema Unico de Saude (SUS - Unified
      Health System) in the city of Rio de Janeiro and to verify its association with
      the characteristics of pregnant women and health services. A cross-sectional
      study was conducted in 2007-2008, using interviews and the analysis of prenatal
      care cards of 2.353 pregnant women attending low risk prenatal care services of
      the SUS. A descriptive analysis of the reasons mentioned by women for the late
      start of prenatal care and hierarchical logistic regression for the
      identification of the factors associated with prenatal care use were performed.
      The absence of a diagnosis of pregnancy and poor access to services were the
      reasons most often reported for the late start of prenatal care. Earlier access
      was found among white pregnant women, who had a higher level of education, were
      primiparous and lived with a partner. The late start of prenatal care was the
      factor most associated with the inadequate number of consultations, also observed
      in pregnant adolescents. Black women had a lower level of adequacy of tests
      performed as well as a lower overall adequacy of prenatal care, considering the
      Programa de Humanizacao do Pre-Natal e Nascimento (PHPN - Prenatal and Delivery
      Humanization Program) recommendations. Strategies for the identification of
      pregnant women at a higher reproductive risk, reduction in organizational
      barriers to services and increase in access to family planning and early
      diagnosis of pregnancy should be prioritized. 

PMID- 24896601
TI  - Assessment of the usability of a nutritional epidemiology computerized system.
AB  - INTRODUCTION: Epidemiological research has been adhering to new technologies,
      such as computer systems, and using the Internet as a tool. Usability is a
      characteristic of a specific product concerning the facility to use it, its speed
      and the facility to learn how to use it. It should also not present errors, or
      these must be easy to solve, in case they occur, thus providing high satisfaction
      to users. OBJECTIVE: To evaluate the usability of the "System of health and
      nutrition monitoring - nutrition of school children" (NUTRISIM). METHODS: A
      sample of 17 Information Technology professionals evaluated the system and
      answered the "Questionnaire for System Usability", which determines the level of
      usability of systems by the Fuzzy Logic. The questionnaire contains 30 questions,
      which are divided into six metrics. The usability of the system determines six
      usability criteria in a large Fuzzy scale. RESULTS: With the exception of the
      metric "error control", all metrics were analyzed as "very good". The metrics
      "error control", "efficiency" and "satisfaction" presented medium amplitude,
      which is a better result in relation to the metrics "easy to learn", "easy to
      remember" and "effectiveness", which was assessed as "high". CONCLUSION: The
      study showed that the system is easy to be learned and used, but the answers are
      scattered. The instrument proved to be a useful tool to monitor and evaluate
      health and dietary intake in epidemiologic studies.

PMID- 24896602
TI  - Analysis of television food advertising on children's programming on "free-to
      air" broadcast stations in Brazil.
AB  - OBJECTIVE: To analyze the content of television food advertising on Brazilian
      'free-to-air' broadcast stations during children's programming. METHODS: This is
      a descriptive study which evaluated the content of food advertising between 08:00
      a.m. and 06:00 p.m. on three Brazilian 'free-to-air' broadcast stations (A, B and
      C). Data collection was performed during 10 week days and weekends. Food
      advertising was organized according to the food group classification from the
      Food Guide for the Brazilian Population. The annual exposure to food advertising
      was obtained considering the national children average exposure to television of
      five daily hours. The chi2 and Fisher's exact test were conducted in order to
      identify differences in the content of television advertising in the morning and
      in the afternoon and between broadcast stations. RESULTS: One hundred and twenty
      six hours of programming were recorded, totalizing 1,369 commercials - 13.8% of
      food. There was major participation of 'sugars and sweets' (48.1%) and 'oils and
      fats' (29.1%) among food advertising and much food publicity in the afternoon
      (15.7%; morning: 12.2%, p = 0.037). Moreover, the broadcast with more audience
      was the one that advertised more food (A: 63.5%; B: 12.2%; C: 24.3%), especially
      'sugar and sweets' (A: 59.2%; B: 43.5%; C: 21.7%). Finally, an annual average
      exposure to 2,735.5 commercials was obtained for Brazilian children, totalizing
      2,106.3 of food rich in sugar and fat publicity. CONCLUSION: Food advertising is
      focused on poor nutritionally food, emphasizing the need for specific
      intervention strategies.

PMID- 24896603
TI  - Relationship between food insecurity and nutritional status of Brazilian children
      under the age of five.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between food
      insecurity and nutritional status of Brazilian children. METHODS: The National
      Demographic and Health Survey 2006 database is available on the worldwide web.
      Thus, the analyzed variables were obtained in this study, including nutritional
      indices, food insecurity and other socioeconomic and demographic variables. The
      height-for-age, weight-for-age and weight-for-height indices were evaluated as
      the Z-score of the World Health Organization reference curves. Food insecurity
      was defined by using the Brazilian Food Insecurity Scale. Averages of three
      indices according to the presence of food insecurity were analyzed, including
      other variables. Linear regression evaluated the effect of food insecurity on the
      Z-score of the three nutritional indices. RESULTS: The sample included 4,817
      children, out of whom 7% had deficit in height, 7% were overweight and 47% had
      food insecurity. It was found that the average of height-for-age, weight-for-age
      and weight-for-height were -0.31, 0.12 and 0.40, respectively, being lower among
      children with food insecurity. CONCLUSION: The regression analysis showed that
      children living with some level of food insecurity have worse rates of height-for
      age, even controlling for demographic and socioeconomic factors.

PMID- 24896604
TI  - Advice for salt, sugar and fat intake habits among adults: a national-based
      study.
AB  - INTRODUCTION: A healthy diet is recognized as an important strategy for promoting
      health as an essential part of non-pharmacological therapy of various health
      problems. OBJECTIVE: To analyze the reported advice for the intake of salt, sugar
      and fat for the Brazilian adults living in urban areas. METHODOLOGY: National
      based cross-sectional study with 12,402 adults interviewed in 100 Brazilian
      cities. RESULTS: The most prevalent advice was to low fat intake (38%), followed
      by the advice to low salt and sugar intake (36%) and sugar (29%). The percentage
      of receiving different advice was similar and more common among women, older
      people, those with a partner, higher economic class, former smokers, active and
      in person with physician diagnoses of hypertension, diabetes and overweight.
      People with white skin color received more advice to eat healthy food, except for
      the orientation to low salt intake. CONCLUSION: The results show a low prevalence
      of advice, which configures a missed opportunity to prevent health problems.
      Although dietary counseling should not be understood only as the transmission of
      advice regarding some nutrients, it is important to develop actions in order to
      qualify services and health professionals, allowing the population to have access
      to qualified information about the benefits of having healthy lifestyles.

PMID- 24896605
TI  - Use of dental services and associated factors among elderly in southern Brazil.
AB  - OBJECTIVE: To analyze the use of dental services and associated factors among
      elderly treated at Family Health Units in southern Brazil. METHODS: This cross
      sectional study evaluated 438 elderly attending Family Health Units in Pelotas,
      southern Brazil. Data were collected using a standardized questionnaire covering
      demographic and socioeconomic variables, in addition to information on time
      elapsed since their last dental visit. Explanatory variables were classified
      according to Andersen and Davidson's model. Clinical variables were obtained by a
      trained dentist. Multivariable Poisson regression models with robust variance
      were used to identify factors associated with the outcome. RESULTS: The
      prevalence of use of dental services in the last 3 years was 41.1% (95%CI 36.5 -
      45.7). Multivariable analysis revealed that the probability of not using dental
      services was higher among individuals who self-assessed their general health as
      poor or very poor (Prevalence Ratio [PR] = 1.36; 95%CI 1.05 - 1.78), with less
      than 8 years of education (< 4 years: PR = 1.43; 95%CI 1.01 - 2.02; 4 to 7 years:
      PR = 1.43; 95%CI 1.00 - 2.04), users of alcohol (PR = 1.31; 95%CI 1.08 - 1.59),
      and those with no teeth (PR = 1.73; 95%CI 1.29 - 2.32). CONCLUSIONS: The low
      prevalence of use of dental services among elderly attending Family Health Units
      in Pelotas, especially among those with poor self-assessed general health, lower
      education level, and without teeth, indicate the need for public policies to
      improve social indicators and general health.

PMID- 24896606
TI  - Adverse reactions to cosmetic products and the Notification System in Health
      Surveillance: a survey.
AB  - INTRODUCTION: This paper is part of a study that investigates the quality of
      cosmetic products and evaluates the cosmetic surveillance system. OBJECTIVE: This
      study presents the results of a research that aimed to describe the point of view
      of the population in terms of the prevalence of Adverse Reactions (AR) and
      information about the surveillance system. METHODS: A structured questionnaire
      was applied to a random sample of 200 people from the administrative staff of the
      Municipal Guard of Rio de Janeiro. RESULTS: 38% of the participants declared AR
      to some cosmetic product used in the past two years. CONCLUSION: To our
      knowledge, this is an unpublished study in Brazil, which presents results
      regarding the estimated prevalence of AR similarly to international studies.

PMID- 24896607
TI  - Dental caries and endemic dental fluorosis in rural communities, Minas Gerais,
      Brazil.
AB  - It is observational, analytical and cross-sectional aimed to evaluate the
      association between severity and prevalence of fluorosis and dental caries in
      rural communities with endemic dental fluorosis in the north state of Minas
      Gerais, Brazil, with fluoride concentrations in water up to 4.8 mg/L. Data were
      collected by one examiner (intra-examiner kappa, 0.96 to 0,95 for caries and
      fluorosis) after toothbrushing. The study included 511 individuals aged 7 - 22
      years, categorized according to age: 7 - 9 years (n = 227), 10 to 12 years (n =
      153), 13 to 15 years (n = 92), 16 to 22 years (n = 39). For the diagnosis of
      dental caries used the criteria of the World Health Organization to measure
      indices DMFT. For fluorosis used the index Thylstrup and Fejerskov (TF),
      dichotomized according to prevalence (TF = 0 and TF > 0) and severity (TF < 4 and
      TF > 5). In the two younger groups, the DMFT and its decay component were higher
      in the group with more severe fluorosis (p < 0.001). This association was not
      found among adolescents and adults (p > 0.05). The association was found between
      the conditions more severe fluorosis and caries in individuals under 12 years. 

PMID- 24896608
TI  - Biochemical characterization of human gluconokinase and the proposed metabolic
      impact of gluconic acid as determined by constraint based metabolic network
      analysis.
AB  - The metabolism of gluconate is well characterized in prokaryotes where it is
      known to be degraded following phosphorylation by gluconokinase. Less is known of
      gluconate metabolism in humans. Human gluconokinase activity was recently
      identified proposing questions about the metabolic role of gluconate in humans.
      Here we report the recombinant expression, purification and biochemical
      characterization of isoform I of human gluconokinase alongside substrate
      specificity and kinetic assays of the enzyme catalyzed reaction. The enzyme,
      shown to be a dimer, had ATP dependent phosphorylation activity and strict
      specificity towards gluconate out of 122 substrates tested. In order to evaluate
      the metabolic impact of gluconate in humans we modeled gluconate metabolism using
      steady state metabolic network analysis. The results indicate that significant
      metabolic flux changes in anabolic pathways linked to the hexose monophosphate
      shunt (HMS) are induced through a small increase in gluconate concentration. We
      argue that the enzyme takes part in a context specific carbon flux route into the
      HMS that, in humans, remains incompletely explored. Apart from the biochemical
      description of human gluconokinase, the results highlight that little is known of
      the mechanism of gluconate metabolism in humans despite its widespread use in
      medicine and consumer products. 

PMID- 24896609
TI  - Growth promoting effect of hyaluronan synthesis promoting substances on Japanese
      eel leptocephali.
AB  - Hyaluronans (HAs) are glycosaminoglycans produced in the bodies of Anguilliform
      and Elopiform leptocephali, and play a role in metabolic energy. In mammals, HA
      synthesis-promoting substances (HASPS) up-regulate the expression of HA synthase
      (HAS) and increase the amount of HA in the body. In this study, Japanese eel
      leptocephali were fed a HASPS containing diet. We analyzed HAS1s and HAS2
      expression, HA content, and their influence on growth. HASPS extracted from
      Grifola frondosa promoted HAS1s and HAS2 mRNA and HA content. Other than mammals,
      these results are first reported in vertebrate. Moreover, HASPS extracted from G.
      frondosa promoted leptocephalus growth. The relationship between growth and HA in
      the leptocephali is not yet clear. However, based on our results we hypothesize
      that HA is involved in the storage of energy, which is metabolized to sugars when
      needed for metabolic energy. 

PMID- 24896610
TI  - Antennal development in the praying mantis (Tenodera aridifolia) highlights
      multitudinous processes in hemimetabolous insect species.
AB  - Insects possess antennae equipped with a large number of segments (flagellomeres)
      on which sensory organs (sensilla) are located. Hemimetabolous insects grow by
      molting until they reach adulthood. In these species, the sensory structures
      develop and mature during each stage of development; new flagellomeres are
      generated at each molt elongating the antennae, and new sensilla appear. The
      praying mantis (Tenodera aridifolia) is a hemimetabolous insect with 7 different
      instars before it reaches adulthood. Because their antennae are provided with an
      atypical sensillar distribution, we previously suggested that their antennae
      develop with a different mechanism to other hemimetaboulous insect species. In
      the present study, we measured the number, length and width of flagellomeres
      along the antennae in nymph and adult mantis Tenodera aridifolia. For this study,
      we developed a new and innovative methodology to reconstruct the antennal
      development based on the length of flagellomeres. We observed and confirmed that
      the antennae of mantises develop with the addition of new segments at two
      distinct sites. In addition, we constructed a complete database of the features
      of the flagellum for each stage of development. From our data, we found that
      sexual dimorphism appears from the 6 instar (larger number and wider
      flagellomeres in males) in accordance with the appearance of their genital
      apparatus. The antennal sexual dimorphism completes at adulthood with longer
      flagellomeres and the emergence of a huge number of grooved peg sensilla in males
      during the last molting, which suggests once again their function as sex
      pheromone receptive sensilla. 

PMID- 24896611
TI  - Free radical-scavenging activities of oligomeric proanthocyanidin from Rhodiola
      rosea L. and its antioxidant effects in vivo.
AB  - This study aimed to determine the antioxidant activity of oligomeric
      proanthocyanidin from Rhodiola rosea L. (OPCRR). The free radical-scavenging
      activities exhibited by OPCRR, as determined by using 1,1-diphenyl-2
      picrylhydrazyl, hydroxyl radical and superoxide anion (?[Formula: see text])
      scavenging assays, were greater than that of vitamin C. The effects of OPCRR on
      the antioxidant enzymes activity and lipid peroxide content in vivo were
      evaluated through three observation biomarkers, including superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in serum, heart,
      liver and brain tissues in mice. The OPCRR significantly enhanced the SOD and GSH
      Px activities, and reduced the MDA content in mice. These results indicated that
      the OPCRR has a great potential to be a natural antioxidant due to its
      considerable antioxidant activities in vitro and in vivo. 

PMID- 24896613
TI  - A cocaine context renews drug seeking preferentially in a subset of individuals.
AB  - Addiction is characterized by a high propensity for relapse, in part because cues
      associated with drugs can acquire Pavlovian incentive motivational properties,
      and acting as incentive stimuli, such cues can instigate and invigorate drug
      seeking behavior. There is, however, considerable individual variation in the
      propensity to attribute incentive salience to reward cues. Discrete and
      localizable reward cues act as much more effective incentive stimuli in some rats
      ('sign-trackers', STs), than others ('goal-trackers', GTs). We asked whether
      similar individual variation exists for contextual cues associated with cocaine.
      Cocaine context conditioned motivation was quantified in two ways: (1) the
      ability of a cocaine context to evoke conditioned hyperactivity and (2) the
      ability of a context in which cocaine was previously self-administered to renew
      cocaine-seeking behavior. Finally, we assessed the effects of intra-accumbens
      core flupenthixol, a nonselective dopamine receptor antagonist, on context
      renewal. In contrast to studies using discrete cues, a cocaine context spurred
      greater conditioned hyperactivity, and more robustly renewed extinguished cocaine
      seeking in GTs than STs. In addition, cocaine context renewal was blocked by
      antagonism of dopamine receptors in the accumbens core. Thus, contextual cues
      associated with cocaine preferentially acquire motivational control over behavior
      in different individuals than do discrete cues, and in these individuals the
      ability of a cocaine context to create conditioned motivation for cocaine
      requires dopamine in the core of the nucleus accumbens. We speculate that
      different individuals may be preferentially sensitive to different 'triggers' of
      relapse. 

PMID- 24896614
TI  - Dopamine receptor blockade modulates the rewarding and aversive properties of
      nicotine via dissociable neuronal activity patterns in the nucleus accumbens.
AB  - The mesolimbic pathway comprising the ventral tegmental area (VTA) and projection
      terminals in the nucleus accumbens (NAc) has been identified as a critical neural
      system involved in processing both the rewarding and aversive behavioral effects
      of nicotine. Transmission through dopamine (DA) receptors functionally modulates
      these effects directly within the NAc. Nevertheless, the neuronal mechanisms
      within the NAc responsible for these bivalent behavioral effects are presently
      not known. Using an unbiased conditioned place preference procedure combined with
      in vivo neuronal recordings, we examined the effects of nicotine reward and
      aversion conditioning on intra-NAc neuronal sub-population activity patterns. We
      report that intra-VTA doses of nicotine that differentially produce rewarding or
      aversive behavioral effects produce opposite effects on sub-populations of fast
      spiking interneurons (FSIs) or medium spiny neurons (MSNs) within the shell
      region of the NAc (NAshell). Thus, while the rewarding effects of intra-VTA
      nicotine were associated with inhibition of FSI and activation of MSNs, the
      aversive effects of nicotine produced the opposite pattern of NAshell neuronal
      population activity. Blockade of DA transmission with a broad-spectrum DA
      receptor antagonist, alpha-flupenthixol, strongly inhibited the spontaneous
      activity of NAshell FSIs, and reversed the conditioning properties of intra-VTA
      nicotine, switching nicotine-conditioned responses from aversive to rewarding.
      Remarkably, DA receptor blockade switched intra-NAshell neuronal population
      activity from an aversion to a reward pattern, concomitant with the observed
      switch in behavioral conditioning effects. 

PMID- 24896615
TI  - Control of the nigrostriatal dopamine neuron activity and motor function by the
      tail of the ventral tegmental area.
AB  - Midbrain dopamine neurons are implicated in various psychiatric and neurological
      disorders. The GABAergic tail of the ventral tegmental area (tVTA), also named
      the rostromedial tegmental nucleus (RMTg), displays dense projections to the
      midbrain and exerts electrophysiological control over dopamine cells of the VTA.
      However, the influence of the tVTA on the nigrostriatal pathway, from the
      substantia nigra pars compacta (SNc) to the dorsal striatum, and on related
      functions remains to be addressed. The present study highlights the role played
      by the tVTA as a GABA brake for the nigrostriatal system, demonstrating a
      critical influence over motor functions. Using neuroanatomical approaches with
      tract tracing and electron microscopy, we reveal the presence of a tVTA-SNc
      dorsal striatum pathway. Using in vivo electrophysiology, we prove that the tVTA
      is a major inhibitory control center for SNc dopamine cells. Using behavioral
      approaches, we demonstrate that the tVTA controls rotation behavior, motor
      coordination, and motor skill learning. The motor enhancements observed after
      ablation of the tVTA are in this regard comparable with the performance-enhancing
      properties of amphetamine, a drug used in doping. These findings demonstrate that
      the tVTA is a major GABA brake for nigral dopamine systems and nigrostriatal
      functions, and they raise important questions about how the tVTA is integrated
      within the basal ganglia circuitry. They also warrant further research on the
      tVTA's role in motor and dopamine-related pathological contexts such as
      Parkinson's disease. 

PMID- 24896616
TI  - Betacyanin biosynthetic genes and enzymes are differentially induced by (a)biotic
      stress in Amaranthus hypochondriacus.
AB  - An analysis of key genes and enzymes of the betacyanin biosynthetic pathway in
      Amaranthus hypochondriacus (Ah) was performed. Complete cDNA sequence of Ah genes
      coding for cyclo-DOPA 5-O glucosyltransferase (AhcDOPA5-GT), two 4, 5-DOPA
      extradiol-dioxygenase isoforms (AhDODA-1 and AhDODA-2, respectively), and a
      betanidin 5-O-glucosyltransferase (AhB5-GT), plus the partial sequence of an
      orthologue of the cytochrome P-450 R gene (CYP76AD1) were obtained. With the
      exception AhDODA-2, which had a closer phylogenetic relationship to DODA-like
      genes in anthocyanin-synthesizing plants, all genes analyzed closely resembled
      those reported in related Caryophyllales species. The measurement of basal gene
      expression levels, in addition to the DOPA oxidase tyrosinase (DOT) activity, in
      different tissues of three Ah genotypes having contrasting pigmentation levels
      (green to red-purple) was determined. Additional analyses were performed in Ah
      plants subjected to salt and drought stress and to two different insect herbivory
      regimes. Basal pigmentation accumulation in leaves, stems and roots of betacyanic
      plants correlated with higher expression levels of AhDODA-1 and AhB5-GT, whereas
      DOT activity levels coincided with pigment accumulation in stems and roots and
      with the acyanic nature of green plants, respectively, but not with pigmentation
      in leaves. Although the abiotic stress treatments tested produced changes in
      pigment levels in different tissues, pigment accumulation was the highest in
      leaves and stems of drought stressed betacyanic plants, respectively. However,
      tissue pigment accumulation in stressed Ah plants did not always correlate with
      betacyanin biosynthetic gene expression levels and/or DOT activity. This effect
      was tissue- and genotype-dependent, and further suggested that other unexamined
      factors were influencing pigment content in stressed Ah. The results obtained
      from the insect herbivory assays, particularly in acyanic plants, also support
      the proposal that these genes could have functions other than betacyanin
      biosynthesis. 

PMID- 24896618
TI  - Achieving immune tolerance in hand and face transplantation: a realistic
      prospect?

PMID- 24896619
TI  - Drug-resistant Th17 cells: culprits in steroid-refractory Crohn's disease?

PMID- 24896621
TI  - Conference scene. The immunology of a successful pregnancy.

PMID- 24896617
TI  - Paternal alcohol exposure reduces alcohol drinking and increases behavioral
      sensitivity to alcohol selectively in male offspring.
AB  - Alcohol use disorder (AUD) is heritable, but the genetic basis for this disease
      remains poorly understood. Although numerous gene variants have been associated
      with AUD, these variants account for only a small fraction of the total risk. The
      idea of inheritance of acquired characteristics, i.e. "epigenetic inheritance,"
      is re-emerging as a proven adjunct to traditional modes of genetic inheritance.
      We hypothesized that alcohol drinking and neurobiological sensitivity to alcohol
      are influenced by ancestral alcohol exposure. To test this hypothesis, we exposed
      male mice to chronic vapor ethanol or control conditions, mated them to ethanol
      naive females, and tested adult offspring for ethanol drinking, ethanol-induced
      behaviors, gene expression, and DNA methylation. We found that ethanol-sired male
      offspring had reduced ethanol preference and consumption, enhanced sensitivity to
      the anxiolytic and motor-enhancing effects of ethanol, and increased Bdnf
      expression in the ventral tegmental area (VTA) compared to control-sired male
      offspring. There were no differences among ethanol- and control-sired female
      offspring on these assays. Ethanol exposure also decreased DNA methylation at the
      BdnfAEpromoter of sire's germ cells and hypomethylation was maintained in the VTA
      of both male and female ethanol-sired offspring. Our findings show that paternal
      alcohol exposure is a previously unrecognized regulator of alcohol drinking and
      behavioral sensitivity to alcohol in male, but not female, offspring. Paternal
      alcohol exposure also induces epigenetic alterations (DNA hypomethylation) and
      gene expression changes that persist in the VTA of offspring. These results
      provide new insight into the inheritance and development of alcohol drinking
      behaviors. 

PMID- 24896622
TI  - A novel biological target for the treatment of psoriatic arthritis.
AB  - Evaluation of: Kavanaugh A, Ritchlin C, Rahman P et al.; on behalf of the PSUMMIT
      1 and -2 Study Groups. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody,
      inhibits radiographic progression in patients with active psoriatic arthritis:
      results of an integrated analysis of radiographic data from the Phase 3,
      multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2
      trials. Ann. Rheum. Dis. 73(6), 1000-1006 (2014). The IL-23/IL-17 axis plays a
      major role in the immunopathogenesis of psoriatic arthritis (PsA), inducing the
      production of proinflammatory cytokines (e.g., IL-1, TNF-alpha, IL-6 and IL8),
      osteoclastogenesis and cartilage degradation. This pathway represents a novel
      target in the treatment of PsA. Ustekinumab is a human monoclonal antibody that
      prevents the human IL-12/IL-23 p40 subunit from binding to the IL12Rbeta1
      receptor chain. The current paper sustains that clinical efficacy of ustekinumab
      is associated with inhibition of radiological progression in active PsA. 

PMID- 24896623
TI  - The HER2 peptide nelipepimut-S (E75) vaccine (NeuVaxTM) in breast cancer patients
      at risk for recurrence: correlation of immunologic data with clinical response.
AB  - Nelipepimut-S (formerly known as E75) is an immunogenic peptide from the HER2
      protein that is highly expressed in breast cancer. The NeuVaxTM (Galena, OR, USA)
      vaccine, nelipepimut-S plus granulocyte-macrophage colony-stimulating factor, is
      designed for the prevention of clinical recurrences in high risk, disease-free
      breast cancer patients. Although cancer vaccines such as NeuVax represent
      promising approaches to cancer immunotherapy, much remains to be elucidated
      regarding their mechanisms of action: particularly given that multiple cancer
      vaccine trials have failed to demonstrate a correlation between immunologic data
      and clinical outcome. Here, we briefly discuss our clinical trial experience with
      NeuVax focusing on immunologic response data and its implication on how the
      immune system may be affected by this peptide vaccine. Most importantly, we
      demonstrate the potential capability of certain immunologic assays to predict
      clinical benefit in our trials. 

PMID- 24896624
TI  - Overview of recombinant human hyaluronidase-facilitated subcutaneous infusion of
      IgG in primary immunodeficiencies.
AB  - Subcutaneous administration of immunoglobulin (IGSC) in a home setting, compared
      with intravenous administration, can improve patient quality of life. During
      IGSC, however, the subcutaneous extracellular matrix inhibits flow and fluid
      entry into the vascular compartment, which limits the amount of drug delivered.
      Recombinant human hyaluronidase (rHuPH20) increases the absorption and dispersion
      of infused fluids and drugs. Results from a Phase III, prospective, open-label,
      noncontrolled study of patients with primary immunodeficiencies indicated that
      IGSC infusion, facilitated by rHuPH20, is well tolerated and delivers infusion
      volumes at treatment intervals and rates equivalent to intravenous
      administration. This drug evaluation provides an overview of rHuPH20 and results
      of clinical studies of IGSC infusion facilitated by rHuPH20 in patients with
      primary immunodeficiencies. 

PMID- 24896625
TI  - Is there any relationship between gene expression of tumor antigens and CD4+ T
      cells in multiple myeloma?
AB  - AIM: The present study aimed at correlating the expression of cancer/testis
      antigens (CTAs) with the expression of genes related to tumor-infiltrating T
      cells. MATERIALS & METHODS: MAGE-C1/CT-7, MAGEA3/6, NY-ESO-1, LAGE-1 and GAGE
      expression were evaluated in 46 bone marrow multiple myeloma (MM) aspirates by RT
      PCR. Expression of FOXP3/CTLA4 and RORyt, as markers for Tregs and Th17 cells,
      respectively, was investigated by quantitative PCR. RESULTS: MAGEC1/CT7 was
      expressed in 66% of MM samples. We did not find correlation between the presence
      of single CTA and expression of CTLA4 or RORyt neither expression of CD4(+) T
      cell markers and the number of CTA simultaneously expressed in the tumor.
      However, we did observe a correlation between the percentage of plasma cells and
      the number of CTAs expressed in the patients' bone marrow. CONCLUSION: Although
      CTAs and immunomodulatory CD4(+) T cells represent potential targets for
      immunotherapy in MM, we did not find association among expression of such genes
      in MM.

PMID- 24896626
TI  - Immunostimulatory effects of Leishmania infantum HSP70 recombinant protein on
      dendritic cells in vitro and in vivo.
AB  - BACKGROUND: Activation of dendritic cells (DCs) has an important role in immunity
      against Leishmania. AIM: We investigated the effect of Leishmania infantum (L.
      infantum) heat shock protein 70 recombinant protein (rHSP70) as a vaccine on DC
      maturation and function. MATERIALS & METHODS: BALB/c mouse splenic DCs were
      isolated and treated with different concentrations of rHSP70. Maturation markers,
      cytokine production and capability of DCs to proliferate allogeneic T cells were
      evaluated. Furthermore, this recombinant protein was injected into BALB/c mice,
      and expression of CD86, CD40 and MHC class II molecules by their splenic DCs were
      evaluated. RESULTS: rHSP70 significantly increases the production of IL-12p70 by
      DCs. It had no effect on allogeneic T-cell proliferation in mixed lymphocyte
      reaction. It increased IFN-gamma and decreased IL-4 cytokine level in mixed
      lymphocyte reaction supernatant. The in vitro study showed that rHSP70 had no
      significant effect neither on the percentage of CD40(+), CD86(+) and MHC class
      II(+) DCs nor on the mean fluorescent intensity. However, in vivo results showed
      that rHSP70 increases the percentage of CD86-, CD40- and MHC class II-expressing
      cells as well as mean fluorescent intensity of CD40 and MHC class II. CONCLUSION:
      This study demonstrated the capability of L. infantum-derived rHSP70 in
      maturating BALB/c mice splenic DCs and in vivo polarization of immunity to a Th1
      response.

PMID- 24896627
TI  - Arguing the misconceptions in allergen-specific immunotherapy.
AB  - Allergen immunotherapy (AIT) has a clear evidence of efficacy and safety, as
      shown by a number of meta-analyses. However, a number of issues limit the use of
      AIT, many of them being not actually supported by solid data from the literature.
      In particular, several contraindications to AIT deserve to be argued, being
      needed to accurately balance in single cases the benefits versus the
      disadvantages. This concerns comorbidities, such as autoimmune diseases and
      malignancies, concomitant drug treatments, particularly beta-blockers and
      angiotensin-converting enzyme inhibitors, pregnancy, patient's age, the severity
      of asthma, allergen polysensitization and the period of starting the treatment.
      Another important aspect producing misconceptions on AIT is the quality of the
      allergen extracts, because currently a patient with respiratory allergy to a
      given source may be prescribed to treat his allergyby products with very
      different quality. Improving characterization and standardization of allergen
      extracts will pave the way to the general acknowledgment of AIT as an effective
      treatment. 

PMID- 24896628
TI  - Kill and spread the word: stimulation of antitumor immune responses in the
      context of radiotherapy.
AB  - Besides the direct, targeted effects of ionizing irradiation (x-ray) on cancer
      cells, namely DNA damage and cell death induction, indirect, nontargeted ones
      exist, which are mediated in large part by the immune system. Immunogenic forms
      of tumor cell death induced by x-ray, including immune modulating danger signals
      like the heat shock protein 70, adenosine triphosphate, and high-mobility group
      box 1 protein are presented. Further, antitumor effects exerted by cells of the
      innate (natural killer cells) as well as adaptive immune system (T cells
      activated by dendritic cells) are outlined. Tumor cell death inhibiting molecules
      such as survivin are introduced as suitable target for molecularly tailored
      therapies in combination with x-ray. Finally, reasonable combinations of immune
      therapies with radiotherapy are discussed. 

PMID- 24896629
TI  - Cellular immunotherapy strategies for Ewing sarcoma.
AB  - Ewing sarcoma is a rare cancer of bone and soft tissues defined by a specific
      chromosomal rearrangement. Preclinical development of immunological treatment
      strategies includes expansion of T cells with native or grafted T-cell receptor
      specificities for Ewing sarcoma-associated intracellular antigens, and T-cell
      engineering with chimeric antigen receptors targeting surface antigens. In vitro
      preactivated NK cells may also have activity in this cancer. Major challenges are
      the heterogeneity of antigen expression in individual Ewing sarcomas, and the
      coexpression of most candidate targets on normal cells. Moreover, homing of
      therapeutic effector cells to both primary and metastatic tumor sites and
      adequate function within the immunosuppressive tumor microenvironment will have
      to be ensured to allow for effective immune targeting of this cancer. 

PMID- 24896630
TI  - Specific therapy to regulate inflammation in rheumatoid arthritis: molecular
      aspects.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease in which persistent
      inflammation of synovial tissue results in a progressive functional decline of
      the joint and premature mortality. TNF inhibitors were the first biological
      disease-modifying antirheumatic drugs (DMARDs) used to treat RA. Since then, new
      biological drugs have emerged, such as inhibitors of IL-1, IL-6 and others, with
      different mechanisms of action that include the depletion of B cells and the
      inhibition of T-cell costimulation. Recently, RA treatments have incorporated the
      use of synthetic DMARDs. This review describes the molecular aspects of the
      mechanisms of action of biological and synthetic DMARDs, discusses the adverse
      effects and limitations of established therapies and analyses the alternative
      approaches to RA treatment. 

PMID- 24896631
TI  - Taming inflammation by targeting cytokine signaling: new perspectives in the
      induction of transplantation tolerance.
AB  - Transplantation tolerance remains an elusive goal, partly due to limitations in
      our understanding of the interplay between inflammatory mediators and their role
      in the activation and regulation of T lymphocytes. Although multiple mechanisms
      acting both centrally and peripherally are responsible for tolerance induction,
      the signaling pathways leading to activation or regulation of adaptive immunity
      are often complex, branched, redundant and modulated by the microenvironment's
      inflammatory milieu. Accumulating evidence clearly indicates that inflammatory
      cytokines limit the tolerogenic potential of immunomodulatory protocols by
      supporting priming of the immune system and counteracting regulatory mechanisms,
      ultimately promoting rejection. In this review, we summarize recent progress in
      the development of novel therapeutics to manipulate this inflammatory environment
      and achievements in targeted inhibition of inflammatory cytokine signaling.
      Ultimately, robust transplant tolerance induction will probably require a
      multifaceted, holistic approach that integrates the various mechanisms of
      tolerance induction, incorporates the dynamic alterations in costimulatory
      requirements of alloreactive T cells, while maintaining endogenous mechanisms of
      immune regulation. 

PMID- 24896634
TI  - Primary low-grade fibromyxoid sarcoma of the kidney in a child with the
      alternative EWSR1-CREB3L1 gene fusion.
AB  - We present the case of a 6-year-old boy with a deceptively bland spindle cell
      renal neoplasm found to harbor the EWSR1-CREB3L1 gene fusion. This fusion has
      recently been described as a variant translocation in low-grade fibromyxoid
      sarcoma (LGFMS), a tumor more typically characterized by a recurrent t(7;16)
      chromosomal translocation, resulting in the fusion of FUS and CREB3L2 genes.
      LGFMS is an indolent tumor with late metastatic potential and a propensity for
      long-term disease recurrence. The tumor is rare in children, with only 33
      published cases. In the pediatric population, it has not previously been reported
      arising in the kidney.

PMID- 24896633
TI  - Epstein-Barr virus-encoded small RNAs (EBERs) are present in fractions related to
      exosomes released by EBV-transformed cells.
AB  - Epstein-Barr virus (EBV) is an oncogenic herpesvirus associated with a number of
      human malignancies of epithelial and lymphoid origin. However, the mechanism of
      oncogenesis is unclear. A number of viral products, including EBV latent proteins
      and non-protein coding RNAs have been implicated. Recently it was reported that
      EBV-encoded small RNAs (EBERs) are released from EBV infected cells and they can
      induce biological changes in cells via signaling from toll-like receptor 3. Here,
      we investigated if these abundantly expressed non-protein coding EBV RNAs (EBER-1
      and EBER-2) are excreted from infected cells in exosomal fractions. Using
      differential ultracentrifugation we isolated exosomes from three EBV positive
      cell lines (B95-8, EBV-LCL, BL30-B95-8), one EBER-1 transfected cell line (293T
      pHEBo-E1) and two EBV-negative cell lines (BL30, 293T-pHEBo). The identity of
      purified exosomes was determined by electron microscopy and western blotting for
      CD63. The presence of EBERs in cells, culture supernatants and purified exosomal
      fractions was determined using RT-PCR and confirmed by sequencing. Purified
      exosomal fractions were also tested for the presence of the EBER-1-binding
      protein La, using western blotting. Both EBER-1 and EBER-2 were found to be
      present not only in the culture supernatants, but also in the purified exosome
      fractions of all EBV-infected cell lines. EBER-1 could also be detected in
      exosomal fractions from EBER-1 transfected 293T cells whilst the fractions from
      vector only transfectants were clearly negative. Furthermore, purified exosomal
      fractions also contained the EBER-binding protein (La), supporting the notion
      that EBERs are most probably released from EBV infected cells in the form of EBER
      La complex in exosomes. 

PMID- 24896635
TI  - Effects of dog rose and watercress extracts on control of green mould decay and
      postharvest quality of orange fruits.
AB  - Minimum inhibitory concentration (MIC) and IC50 values and total phenolics of dog
      rose fruits were 72.5-80 MUL mL(- 1), 130 MUg mL(- 1) and 5.7 mg GA g(- 1),
      respectively. The Fashand watercress population and dog rose extracts exhibited
      mycelia growth inhibition values of 45.08% and 37.12%, respectively. The results
      of in vivo study indicated that the treatment of inoculated fruits with both
      methanol extracts especially the watercress plant extract considerably controls
      the citrus fruits decay (Penicillium digitatum) up to 73%. In conclusion,
      methanol extracts of dog rose fruits and especially watercress plant had the
      potential to be used against citrus green mould and even for the improvement of
      postharvest quality of orange fruits. 

PMID- 24896636
TI  - Glutathione metabolism in Candida albicans resistant strains to fluconazole and
      micafungin.
AB  - Currently available therapies for candidiasis are based on antifungal drugs
      belonging to azole and echinocandin families that interfere with different
      aspects of fungal metabolism. These drugs, beyond their specific effects, elicit
      also a cellular stress including an unbalance of redox state that is counteracted
      not only utilizing antioxidant species but also increasing the outcome export by
      transporters to detoxify the internal environment. These cellular actions are
      both based on the cytosolic concentration of reduced glutathione (GSH). In this
      paper we investigated the effects of two antifungal drugs fluconazole and
      micafungin on the redox state of the cell in C. albicans to understand if the
      resistance to these drugs is accompanied by variation of glutathione metabolism.
      Analyses of resistant strains showed a marked difference in glutathione contents
      in strains resistant to fluconazole (CO23RFLC) or micafungin (CO23RFK). In
      CO23RFLC, the total amount of glutathione was more than doubled with respect to
      CO23RFK thanks to the increased activity of gamma-glutamilcysteine synthetase,
      the key enzyme involved in GSH synthesis. We demonstrated that the GSH increase
      in CO23RFLC conferred to this strain a clear advantage in counteracting oxidative
      toxic agents while assignment of other roles, such as a more efficient
      elimination of the drug from the cell, should be considered more speculative. As
      far as MCFG resistance is concerned, from our data a role of glutathione
      metabolism in supporting this condition is not evident. Overall our data indicate
      that glutathione metabolism is differently affected in the two resistant strains
      and that glutathione system may play an important role in the global organization
      of C.albicans cells for resistance to fluconazole. Such scenario may pave the way
      to hypothesize the use of oxidant drugs or inhibitors able to deplete reduced
      glutathione level as a novel approach, for counteracting the resistance to this
      specific antifungal drug. 

PMID- 24896638
TI  - Space use of African wild dogs in relation to other large carnivores.
AB  - Interaction among species through competition is a principle process structuring
      ecological communities, affecting behavior, distribution, and ultimately the
      population dynamics of species. High competition among large African carnivores,
      associated with extensive diet overlap, manifests in interactions between
      subordinate African wild dogs (Lycaon pictus) and dominant lions (Panthera leo)
      and spotted hyenas (Crocuta crocuta). Using locations of large carnivores in
      Hluhluwe-iMfolozi Park, South Africa, we found different responses from wild dogs
      to their two main competitors. Wild dogs avoided lions, particularly during
      denning, through a combination of spatial and temporal avoidance. However, wild
      dogs did not exhibit spatial or temporal avoidance of spotted hyenas, likely
      because wild dog pack sizes were large enough to adequately defend their kills.
      Understanding that larger carnivores affect the movements and space use of other
      carnivores is important for managing current small and fragmented carnivore
      populations, especially as reintroductions and translocations are essential tools
      used for the survival of endangered species, as with African wild dogs. 

PMID- 24896639
TI  - Curriculum reform at Chinese medical schools: what have we learned?
AB  - INTRODUCTION: Curriculum reform at Chinese medical schools has attracted a lot of
      attention recently. Several leading medical schools in China have undergone
      exploratory reforms and in so doing, have accumulated significant experience and
      have made considerable progress. METHODS: An analysis of the reforms conducted by
      38 Chinese medical colleges that were targeted by the government for upgrade was
      performed. Drawing from both domestic and international literature, we designed a
      questionnaire to determine what types of curricular reforms have occurred at
      these institutions and how they were implemented. Major questions touched upon
      the purpose of the reforms, curricular patterns, improvements in teaching methods
      post-reform, changes made to evaluation systems post-reform, intra-university
      reform assessment, and what difficulties the schools faced when instituting the
      reforms. Besides the questionnaire, relevant administrators from each medical
      school were also interviewed to obtain more qualitative data. RESULTS: Out of the
      38 included universities, twenty-five have undergone major curricular reforms.
      Among them, 60.0% adopted an organ system-based curriculum model, 32.0% adopted a
      problem-based curriculum model, and 8.0% adopted a hybrid curriculum model. About
      60.0% of the schools' reforms involved both the "pre-clinical" and the "clinical"
      curricula, 32.0% of the schools' reforms were limited to the "pre-clinical"
      curricula, and 8.0% of the schools' reforms only involved the "clinical"
      curricula. Following curricular reform, 60.0% of medical schools experienced an
      overall reduction in teaching hours, 76.0% reported an increase in their
      students' clinical skills, and 60.0% reported an increase in their students'
      research skills. DISCUSSION: Medical curricular reform is still in its infancy in
      China. The republic's leading medical schools have engaged in various approaches
      to bring innovative teaching methods to their respective institutions. However,
      due to limited resources and the shackle of traditional pedagogical beliefs among
      many faculty and administrators, progress has been significantly hindered.
      Despite these and other challenges, many medical schools report positive initial
      results from the reforms that they have enacted. Although the long term effects
      of such reforms remain unclear, curricular reform appears to be the inevitable
      solution to China's growing need for high-quality medical doctors.

PMID- 24896637
TI  - Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild
      neurological and behavioral impairments.
AB  - Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron
      homeostasis in vertebrates. Two global knockout mouse models have been generated
      to explore the role of Irp2 in regulating iron metabolism. While both mouse
      models show that loss of Irp2 results in microcytic anemia and altered body iron
      distribution, discrepant results have drawn into question the role of Irp2 in
      regulating brain iron metabolism. One model shows that aged Irp2 deficient mice
      develop adult-onset progressive neurodegeneration that is associated with axonal
      degeneration and loss of Purkinje cells in the central nervous system. These mice
      show iron deposition in white matter tracts and oligodendrocyte soma throughout
      the brain. A contrasting model of global Irp2 deficiency shows no overt or
      pathological signs of neurodegeneration or brain iron accumulation, and display
      only mild motor coordination and balance deficits when challenged by specific
      tests. Explanations for conflicting findings in the severity of the clinical
      phenotype, brain iron accumulation and neuronal degeneration remain unclear.
      Here, we describe an additional mouse model of global Irp2 deficiency. Our aged
      Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes
      while iron content is significantly reduced in neurons. Ferritin and transferrin
      receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in
      the brain from Irp2-/- mice. These mice show impairments in locomotion,
      exploration, motor coordination/balance and nociception when assessed by
      neurological and behavioral tests, but lack overt signs of neurodegenerative
      disease. Ultrastructural studies of specific brain regions show no evidence of
      neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron
      metabolism causing cellular dysfunction that ultimately leads to mild
      neurological, behavioral and nociceptive impairments. 

PMID- 24896640
TI  - Association of cardiorespiratory fitness and overweight with risk of type 2
      diabetes in Japanese men.
AB  - OBJECTIVE: Existing evidence is limited on what extent fitness can counterbalance
      type 2 diabetes mellitus (T2DM) risk associated with obesity. We investigated the
      joint association of weight status and estimated VO2max, a marker of fitness,
      with the risk of developing T2DM among Japanese men using haemoglobin A1c and
      fasting glucose criterion. METHODS: The present study included 3,523 male
      employees aged 18-61 years without diabetes who provided health check-up and
      fitness data in Japan in 2003-2005. We calculated hazard ratios and 95%
      confidence intervals for incident diabetes using the Cox regression model.
      RESULTS: During a mean follow-up of 6.0 years, 199 men developed diabetes.
      Multivariable-adjusted hazard ratios (95% confidence interval) of diabetes were
      1.00 (reference), 1.44 (1.01-2.07), and 1.48 (1.03-2.13) for the highest through
      the lowest tertile of fitness (P for trend  = 0.04). Additional adjustment for
      body mass index largely attenuated the association of fitness with diabetes.
      Joint analysis showed that adjusted hazard ratios of diabetes were 1.00, 1.32,
      2.94, and 1.83 in normal weight high-fit men, normal weight low-fit men,
      overweight high-fit men, and overweight low-fit men, respectively. CONCLUSION:
      The results suggest that weight control is more important than fitness in
      prevention of type 2 diabetes in Japanese men.

PMID- 24896642
TI  - Glucocorticoid receptors expression and histopathological types in children with
      nephrotic syndrome.
AB  - Abstract Background: Some children with idiopathic nephrotic syndrome (NS)
      patients fail to respond even when given high dose of steroid. The aim of this
      study was to assess the GCR expression on the T lymphocytes of children with NS
      and its relation to the response to steroid and to histopathological type.
      METHODS: Forty-six pediatric patients with idiopathic NS and 20 age and sex
      matched apparently healthy children as controls were included. Flow cytometry was
      employed to determine the percentage of CD3+/GCR+ cells which then correlated
      with pattern of steroid response. Renal biopsy was done for steroid-dependent and
      steroid-resistant cases for determination of the underlying histopathological
      type. RESULTS: The mean percentage of T lymphocyte expression of GCRs (CD3+/GCR)
      was significantly higher in early steroid responders than in late responders and
      was slightly lower than the controls. There was a significantly lower GCRs
      expression in steroid-resistant patients in comparison to early responders, late
      responders and controls. Renal biopsy showed that most cases of late responders
      were of the focal segmental glomerulosclerosis (FSGS) type. The mean percentage
      of lymphocyte expression of GCRs was significantly higher in patients with
      minimal change disease (MCD) compared to patients with FSGS. CONCLUSION:
      Evaluation of the expression of intracellular GCRs in T lymphocytes at time of
      diagnosis of NS can predict the response to steroid therapy and can help in
      determination of the outcome of NS patients regarding future relapses.

PMID- 24896641
TI  - Metformin attenuates palmitate-induced endoplasmic reticulum stress, serine
      phosphorylation of IRS-1 and apoptosis in rat insulinoma cells.
AB  - Lipotoxicity refers to cellular dysfunctions caused by elevated free fatty acid
      levels playing a central role in the development and progression of obesity
      related diseases. Saturated fatty acids cause insulin resistance and reduce
      insulin production in the pancreatic islets, thereby generating a vicious cycle,
      which potentially culminates in type 2 diabetes. The underlying endoplasmic
      reticulum (ER) stress response can lead to even beta-cell death (lipoapoptosis).
      Since improvement of beta-cell viability is a promising anti-diabetic strategy,
      the protective effect of metformin, a known insulin sensitizer was studied in rat
      insulinoma cells. Assessment of palmitate-induced lipoapoptosis by fluorescent
      microscopy and by detection of caspase-3 showed a significant decrease in
      metformin treated cells. Attenuation of beta-cell lipotoxicity was also revealed
      by lower induction/activation of various ER stress markers, e.g. phosphorylation
      of eukaryotic initiation factor 2alpha (eIF2alpha), c-Jun N-terminal kinase
      (JNK), insulin receptor substrate-1 (IRS-1) and induction of CCAAT/enhancer
      binding protein homologous protein (CHOP). Our results indicate that the beta
      cell protective activity of metformin in lipotoxicity can be at least partly
      attributed to suppression of ER stress. 

PMID- 24896643
TI  - Intercellular communication through contacts between continuous pseudopodial
      extensions in a macrophage-like cell line.
AB  - Cell-to-cell information exchange mediated by membrane protrusions in tunneling
      nanotubes (TNTs) has been widely described in distinct cell lines. Here, we
      describe a new form of direct intercellular communication in a murine macrophage
      like cell line that is mediated by pseudopodial fusions that form over scraped
      plastic tissue culture surfaces along scratch lines. These structures are capable
      of forming intercellular, tunnel-like channels (inter-pseudopodial axis
      connections) that can be differentiated from TNTs based on length, thickness,
      tandem arrangement along an axis, pseudopodial origin and permanency. These
      channels were able to exchange membrane lipids and contain particles 0.5 MUm or
      lesser in diameter between cells and might represent an additional biological
      function of pseudopodia.

PMID- 24896644
TI  - Validation of heart rate derived from a physiological status monitor-embedded
      compression shirt against criterion ECG.
AB  - Firefighters are subject to extreme environments and high physical demands when
      performing duty-related tasks. Recently, physiological status monitors (PSM) have
      been embedded into a compression shirt to enable firefighters to measure,
      visualize, log, and transmit vital metrics such as heart rate (HR) to aid in
      cardiovascular risk identification and mitigation, thereby attempting to improve
      the health, fitness, and safety of this population. The purpose of this study was
      to validate HR recorded by the PSM-embedded compression shirt against a criterion
      standard laboratory ECG-derived HR when worn concurrently with structural
      firefighting personal protective equipment (PPE) during four simulated
      firefighting activities. Ten healthy, college-age men (mean +/- SD: age: 21 +/- 1
      yr; body mass: 91 +/- 10 kg; body mass index: 26.9 +/- 3.1 kg/m(2)) completed
      four tasks that are routinely performed during firefighting operations: outdoor
      fast-paced walking (FW), treadmill walking (TW), searching/crawling (SC), and
      ascending/descending stairs (AD). They wore the PSM-embedded compression shirt
      under structural firefighting PPE. HR was recorded concurrently by the PSM
      embedded compression shirt and a portable metabolic measurement system
      accompanied with a standard 12-lead electrocardiograph that was used to provide
      criterion measures of HR. For all four tasks combined there was very high
      correlation of PSM and ECG HR (r > 0.99; SEE 0.84 /min) with a mean difference
      (bias) of -0.02 /min and limits of agreement of -0.07 to 0.02 /min. For
      individual tasks, the correlations were also high (r-values = 0.99; SEE 0.81
      0.89). The mean bias (limits of agreement) was: FW 0.03 (-0.09 to 0.14); TW 0.04
      (-0.05 to 0.12); SC -0.01 (-0.12 to 0.10); AD -0.13 (-0.21 to -0.04) /min. These
      findings demonstrate that the PSM-embedded compression shirt provides a valid
      measure of HR during simulated firefighting activities when compared with a
      standard 12-lead ECG.

PMID- 24896646
TI  - Molecular mapping of sorbent selectivities with respect to isolation of Arctic
      dissolved organic matter as measured by Fourier transform mass spectrometry.
AB  - The objectives of this study were to identify molecular features characteristic
      to arctic DOM from the Kolyma River basin and to elucidate structural imprints
      induced by a choice of the sorption technique. To achieve this goal, DOM was
      isolated from the Kolyma River basin with a use of three nonionic sorbents:
      Amberlite XAD-8 resin, PPL- and C18 - SPE cartridges, and one anion exchanging
      resin-diethylaminoethyl (DEAE) -cellulose. The structural studies were conducted
      with a use of electrospray ionization Fourier Transform Ion Cyclotron Resonance
      (ESI FT-ICR) mass spectrometry and liquid state (1)H NMR spectroscopy. The DOM
      isolates obtained with a use of PPL and C18 cartridges were characterized with
      higher content of aliphatic compounds as compared to XAD-8 and DEAE-isolates. In
      total, for all arctic DOM isolates we observed predominance of hydrogen saturated
      compounds with high H/C values of identified formulas from FT-ICR MS data. (1)H
      NMR spectroscopy studies have confirmed this trend and revealed high contribution
      of alkyl-chain protons into the spectral density of the arctic DOM reaching 43%
      for PPL isolates. 

PMID- 24896647
TI  - Estimation of C-index for cox proportional hazards model with censored biomarker
      covariate subject to limits of detection.
AB  - Biomarkers play an important role to predict the time to event of interest. To
      evaluate the prediction performance of biomarkers, Cox proportional hazards model
      and Harrell's C-index have been widely used. However, when some of the biomarker
      measurements are not fully observed due to detection limits of given instrument,
      evaluation may become complicated. We estimate the Cox model and concordance
      probability in the presence of censored biomarker data. Simulation study
      demonstrates that the proposed method outperforms over the simple ad hoc method.
      Our approach is especially useful to evaluate discrimination potential of the
      biomarker regardless of variant detection limits. 

PMID- 24896645
TI  - Natural progression of childhood asthma symptoms and strong influence of sex and
      puberty.
AB  - RATIONALE: Asthma prevalence, onset, remission and relapse, and healthcare use
      have been intensively studied. However, asthma symptom progression through
      childhood and adolescence has not been well studied, in part due to the
      challenges in obtaining consistent and robust long-term follow-up data on a large
      series of subjects with asthma. OBJECTIVES: To use the asthma diary symptom data
      of the Childhood Asthma Management Program placebo group (5 yr, 418 subjects, and
      total 564,518 records) to establish sex-specific high-resolution time courses of
      the natural progression of asthma symptoms through childhood and adolescence.
      METHODS: We used the asthma diary symptom code as a measure of daily disease
      severity. Annual records of Tanner stage were used to determine the influence of
      puberty on severity. A data alignment technique was used to derive 13-year time
      courses of mean symptoms and mean Tanner stage. MEASUREMENTS AND MAIN RESULTS:
      Data analyses showed three age- and sex-related phases of asthma symptom
      progression: Phase 1 (ages 5 and 6 yr)-greater severity in boys; Phase 2 (ages 7
      to 9 yr)-no sex difference in severity; and Phase 3 (age 10-17 yr)-greater
      severity in girls. The continuous decline of symptoms in both sexes stops
      abruptly at the onset of puberty. CONCLUSIONS: The severity of asthma symptoms
      varies through childhood and adolescence, and patterns differ by sex. Puberty has
      a strong influence on symptom progression in both sexes. Progression of symptoms
      is a distinct aspect of asthma epidemiology.

PMID- 24896649
TI  - Height, socioeconomic and subjective well-being factors among U.S. women, ages 49
      79.
AB  - BACKGROUND: A vast literature has associated height with numerous factors,
      including biological, psychological, socioeconomic, anthropologic, genetic,
      environmental, and ecologic, among others. The aim of this study is to examine,
      among U.S. women, height factors focusing on health, income, education,
      occupation, social activities, religiosity and subjective well-being.
      METHODS/FINDINGS: Data are from the Women's Health Initiative (WHI) Observational
      Study. Participants are 93,676 relatively healthy women ages 49-79; 83% of whom
      are White, 17% Non-White. Statistical analyses included descriptive statistics,
      chi-square and multivariable covariance analyses. The mean height of the total
      sample is 63.67 inches. White women are significantly taller than Non-White
      women, mean heights 63.68 vs. 63.63 inches (p= 0.0333). Among both Non-White and
      White women height is associated with social behavior, i.e. attendance at
      clubs/lodges/groups. Women who reported attendance 'once a week or more often'
      were taller than those who reported 'none' and 'once to 3 times a month'. Means
      in inches are respectively for: White women-63.73 vs. 63.67 and 63.73 vs. 63.67,
      p = 0.0027. p = 0.0298; Non-White women: 63.77 vs. 63.61 and 63.77 vs. 63.60, p =
      0.0050, P = 0.0094. In both White and Non-White women, income, education and
      subjective well-being were not associated with height. However, other factors
      differed by race/ethnicity. Taller White women hold or have held
      managerial/professional jobs-yes vs. no-63.70 vs. 63.66 inches; P = 0.036; and
      given 'a little' strength and comfort from religion' compared to 'none' and 'a
      great deal', 63.73 vs. 63.66 P = 0.0418 and 63.73 vs. 63.67, P = 0.0130. Taller
      Non-White women had better health-excellent or very good vs. good, fair or poor
      63.70 vs. 63.59, P = 0.0116. CONCLUSIONS: Further research in diverse populations
      is suggested by the new findings: being taller is associated with social
      activities -frequent attendance clubs/lodges/groups", and with 'a little' vs.
      'none' or 'great deal' of strength and comfort from religion.

PMID- 24896651
TI  - Oxidative quenching of quinone methide adducts reveals transient products of
      reversible alkylation in duplex DNA.
AB  - ortho-Quinone methides (ortho-QM) and para-quinone methides are generated by
      xenobiotic metabolism of numerous compounds including environmental toxins and
      therapeutic agents. These intermediates are highly electrophilic and have the
      potential to alkylate DNA. Assessing their genotoxicity can be difficult when all
      or some of their resulting adducts form reversibly. Stable adducts are most
      easily detected but are not necessarily the most prevalent products formed
      initially as DNA repair commences. Selective oxidation of ortho-QM-DNA adducts by
      bis[(trifluoroacetoxy)iodo]benzene (BTI) rapidly quenches their reversibility to
      prevent QM regeneration and allows for observation of the kinetic products. The
      resulting derivatives persist through standard enzymatic digestion,
      chromatography, and mass spectral analysis. The structural standards required for
      this approach have been synthesized and confirmed by two-dimensional NMR
      spectroscopy. The adducts of dA N(6), dG N1, dG N(2), and guanine N7 are
      converted to the expected para-quinol derivatives within 5 min after addition of
      BTI under aqueous conditions (pH 7). Concurrently, the adduct of dA N1 forms a
      spiro derivative comparable to that characterized previously after oxidation of
      the corresponding dC N3 adduct. By application of this oxidative quenching
      strategy, the dC N3 and dA N1 adducts have been identified as the dominant
      products formed by both single- and double-stranded DNA under initial conditions.
      As expected, however, these labile adducts dissipate within 24 h if not quenched
      with BTI. Still, the products favored by kinetics are responsible for inducing
      the first response to ortho-QM exposure in cells, and hence, they are also key to
      establishing the relationship between biological activity and molecular
      structure. 

PMID- 24896650
TI  - Manganese-induced atypical parkinsonism is associated with altered Basal Ganglia
      activity and changes in tissue levels of monoamines in the rat.
AB  - Manganese neurotoxicity is associated with motor and cognitive disturbances known
      as Manganism. However, the mechanisms underlying these deficits remain unknown.
      Here we investigated the effects of manganese intoxication on motor and non-motor
      parkinsonian-like deficits such as locomotor activity, motor coordination,
      anxiety and "depressive-like" behaviors. Then, we studied the impact of this
      intoxication on the neuronal activity, the globus pallidus (GP) and subthalamic
      nucleus (STN). At the end of experiments, post-mortem tissue level of the three
      monoamines (dopamine, norepinephrine and serotonin) has been determined. The
      experiments were carried out in adult Sprague-Dawley rats, daily treated with
      MnCl2 (10 mg/kg/, i.p.) for 5 weeks. We show that manganese progressively reduced
      locomotor activity as well as motor coordination in parallel with the
      manifestation of anxiety and "depressive-like" behaviors. Electrophysiological
      results show that, while majority of GP and STN neurons discharged regularly in
      controls, manganese increased the number of GP and STN neurons discharging
      irregularly and/or with bursts. Biochemical results show that manganese
      significantly decreased tissue levels of norepinephrine and serotonin with
      increased metabolism of dopamine in the striatum. Our data provide evidence that
      manganese intoxication is associated with impaired neurotransmission of
      monoaminergic systems, which is at the origin of changes in basal ganglia
      neuronal activity and the manifestation of motor and non-motor deficits similar
      to those observed in atypical Parkinsonism. 

PMID- 24896654
TI  - Chemometrics models for assessment of oxidative stress risk in chrome
      electroplating workers.
AB  - Oxidative stress is the main cause of hexavalant chromium-induced damage in
      chrome electroplating workers. The main goal of this study is toxicity analysis
      and the possibility of toxicity risk categorizing in the chrome electroplating
      workers based on oxidative stress parameters as prognostic variables. We assessed
      blood chromium levels and biomarkers of oxidative stress such as lipid
      peroxidation, thiol (SH) groups and antioxidant capacity of plasma. Data were
      subjected to principle component analysis (PCA) and artificial neuronal network
      (ANN) to obtain oxidative stress pattern for chrome electroplating workers. Blood
      chromium levels increased from 4.42 ppb to 10.6 ppb. Induction of oxidative
      stress was observed by increased in lipid peroxidation (22.38 +/- 10.47 MUM
      versus 14.74 +/- 4.82 MUM, p < 0.0008), decreased plasma antioxidant capacity
      (3.17 +/- 1.35 MUM versus 7.74 +/- 4.45 MUM, p < 0.0001) and plasma total thiol
      (SH groups) (0.21 +/- 0.07 MUM versus 0.45 +/- 0.41 MUM, p < 0.0042) in
      comparison to controls. Based on the oxidative parameters, two groups were
      identified by PCA methods. One category is workers with the risk of oxidative
      stress and second group is subjects with probable risk of oxidative stress
      induction. ANN methods can predict oxidative-risk category for assessment of
      toxicity induction in chrome electroplaters. The result showed multivariate
      modeling can be interpreted as the induced biochemical toxicity in the workers
      exposed to hexavalent chromium. Different occupation groups were assessed on the
      basis of risk level of oxidative stress which could further justify proceeding
      engineering control measures. 

PMID- 24896655
TI  - Ovarian tissue vitrification is more efficient than slow freezing in protecting
      oocyte and granulosa cell DNA integrity.
AB  - Ovarian tissue cryopreservation is the primary treatment modality currently
      available to women at risk of losing their ovarian function due to cytotoxic
      therapy. However, the impact of these techniques on the oocyte DNA integrity is
      not elucidated. Here we have investigated the effect of vitrification and
      conventional slow freezing of eight week old Swiss albino mouse ovarian tissues
      on the oocyte and granulosa cell DNA integrity using the comet assay. The
      intracellular levels of reactive oxygen species in oocytes was measured by 2',7'
      dichlorodihydrofluorescein diacetate fluorescence. The cryopreservation of
      ovarian tissue by the slow freezing technique resulted in a significantly higher
      level of DNA fragmentation in oocytes in comparison to vitrification (p < 0.05)
      whereas DNA fragmentation in granulosa cells was significantly higher than the
      control (p < 0.01). Further, reactive oxygen species were significantly elevated
      in oocytes derived from slow freezing when compared to vitrification (p < 0.05).
      Therefore, we conclude that the ovarian tissue slow freeze-thawing makes the
      oocyte and granulosa cells more vulnerable to DNA damage whereas vitrification
      appears to be a safer method than slow freezing for ovarian tissue
      cryopreservation.

PMID- 24896656
TI  - An expanded training program for endosonographers improved self-diagnosed
      accuracy of endoscopic ultrasound-guided fine-needle aspiration cytology of the
      pancreas.
AB  - OBJECTIVE: Rapid on-site evaluation (ROSE) of cytologic adequacy improves the
      diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration (EUS
      FNA). However, on-site advice from a cytotechnologist or cytopathologist is not
      always available during EUS-FNA. To enhance endosonographers' ability to assess
      the adequacy of EUS-FNA specimens, we designed an intensive, 2-h interactive
      training program. The aim of this study was to determine the usefulness of the
      program. METHODS: Four cytological pictures were selected by a trained
      cytotechnologist and board-certified cytopathologist from each of the seven
      patients who underwent EUS-FNA for pancreatic mass in Okayama University
      Hospital. In total, 28 pictures were used in this study. Twenty endosonographers
      and 14 cytologists with different levels of EUS-FNA experience evaluated
      cytological pictures independently before and after the training program.
      RESULTS: Endosonographers' skill in evaluating the adequacy of EUS-FNA specimens
      was significantly improved after the completion of the training program (p <
      0.001). In contrast, almost all cytologists correctly judged the adequacy of the
      specimens before taking the training program. CONCLUSIONS: This intensive, 2-h
      interactive training program is useful for endosonographers and capable of
      improving ROSE of EUS-FNA specimens.

PMID- 24896652
TI  - A dnaN plasmid shuffle strain for rapid in vivo analysis of mutant Escherichia
      coli beta clamps provides insight into the role of clamp in umuDC-mediated cold
      sensitivity.
AB  - The E. coli umuDC gene products participate in two temporally distinct roles:
      UmuD2C acts in a DNA damage checkpoint control, while UmuD'2C, also known as DNA
      polymerase V (Pol V), catalyzes replication past DNA lesions via a process termed
      translesion DNA synthesis. These different roles of the umuDC gene products are
      managed in part by the dnaN-encoded beta sliding clamp protein. Co-overexpression
      of the beta clamp and Pol V severely blocked E. coli growth at 30 degrees C. We
      previously used a genetic assay that was independent of the ability of beta clamp
      to support E. coli viability to isolate 8 mutant clamp proteins (betaQ61K,
      betaS107L, betaD150N, betaG157S, betaV170M, betaE202K, betaM204K and betaP363S)
      that failed to block growth at 30 degrees C when co-overexpressed with Pol V. It
      was unknown whether these mutant clamps were capable of supporting E. coli
      viability and normal umuDC functions in vivo. The goals of this study were to
      answer these questions. To this end, we developed a novel dnaN plasmid shuffle
      assay. Using this assay, betaD150N and betaP363S were unable to support E. coli
      viability. The remaining 6 mutant clamps, each of which supported viability, were
      indistinguishable from beta+ with respect to umuDC functions in vivo. In light of
      these findings, we analyzed phenotypes of strains overexpressing either beta
      clamp or Pol V alone. The strain overexpressing beta+, but not those expressing
      mutant beta clamps, displayed slowed growth irrespective of the incubation
      temperature. Moreover, growth of the Pol V-expressing strain was modestly slowed
      at 30 degrees , but not 42 degrees C. Taken together, these results suggest the
      mutant clamps were identified due to their inability to slow growth rather than
      an inability to interact with Pol V. They further suggest that cold sensitivity
      is due, at least in part, to the combination of their individual effects on
      growth at 30 degrees C. 

PMID- 24896658
TI  - Peromyscus (deer mice) as developmental models.
AB  - Deer mice (Peromyscus) are the most common native North American mammals, and
      exhibit great natural genetic variation. Wild-derived stocks from a number of
      populations are available from the Peromyscus Genetic Stock Center (PGSC). The
      PGSC also houses a number of natural variants and mutants (many of which appear
      to differ from Mus). These include metabolic, coat-color/pattern, neurological,
      and other morphological variants/mutants. Nearly all these mutants are on a
      common genetic background, the Peromyscus maniculatus BW stock. Peromyscus are
      also superior behavior models in areas such as repetitive behavior and pair
      bonding effects, as multiple species are monogamous. While Peromyscus development
      generally resembles that of Mus and Rattus, prenatal stages have not been as
      thoroughly studied, and there appear to be intriguing differences (e.g., longer
      time spent at the two-cell stage). Development is greatly perturbed in crosses
      between P. maniculatus (BW) and Peromyscus polionotus (PO). BW females crossed to
      PO males produce growth-restricted, but otherwise healthy, fertile offspring
      which allows for genetic analyses of the many traits that differ between these
      two species. PO females crossed to BW males produce overgrown but severely
      dysmorphic conceptuses that rarely survive to late gestation. There are likely
      many more uses for these animals as developmental models than we have described
      here. Peromyscus models can now be more fully exploited due to the emerging
      genetic (full linkage map), genomic (genomes of four stocks have been sequenced)
      and reproductive resources.

PMID- 24896659
TI  - Vertebrate female germline--the acquisition of femaleness.
AB  - The cellular and molecular characteristics of female germ cells have primarily
      been studied in the mammalian ovary. In most female mammals, all primordial germ
      cells (PGCs) develop into oocytes early during ovary formation, and germline stem
      cells are few in number or absent in postnatal ovaries (Lei L, Spradling AC.
      Female mice lack adult germ-line stem cells but sustain oogenesis using stable
      primordial follicles. Proc Natl Acad Sci USA 2013, 110:8585-8590). Research
      efforts in the field have largely focused on meiosis and follicular development,
      but a fundamental question regarding establishment of femaleness, which is very
      important to understand the 'female' germline, has not been discussed
      sufficiently. Recent work has revealed the presence of germline stem cells in the
      vertebrate ovary, using the teleost fish, medaka (Oryzias latipes) (Nakamura S,
      Kobayashi K, Nishimura T, Higashijima S, Tanaka, M. Identification of germline
      stem cells in the ovary of teleost medaka. Science 2010, 328:1561-1563). This
      discovery allows direct comparison between female and male germline stem cells
      and raises an interesting and heretofore unaddressed issue regarding femaleness
      of germline stem cells. In this article, the germ cell behavior in the ovaries of
      different species is reviewed and compared, the molecular mechanisms underlying
      the generation of female germ cells are discussed, and the relationship between
      female germ cells and the surrounding somatic cells is examined.

PMID- 24896660
TI  - Stereoselective formation of tetrahydrofuran rings via [3 + 2] annulation: total
      synthesis of Plakortone L.
AB  - The [3 + 2] annulation of 2,3-O-isopropylidene-aldehydo-aldose with methallyl
      ether leads to the stereoselective formation of a substituted tetrahydrofuran
      system, which is converted to a bicyclic lactone derivative via consecutive
      deprotection, oxidative cleavage of the terminal diol, oxidation of the resulting
      lactol, and Barton-McCombie deoxygenation. The efficiency of this process was
      demonstrated by the first total synthesis of Plakortone L. 

PMID- 24896657
TI  - Development of the embryonic and larval peripheral nervous system of Drosophila.
AB  - The peripheral nervous system (PNS) of embryonic and larval stage Drosophila
      consists of diverse types of sensory neurons positioned along the body wall.
      Sensory neurons, and associated end organs, show highly stereotyped locations and
      morphologies. Many powerful genetic tools for gene manipulation available in
      Drosophila make the PNS an advantageous system for elucidating basic principles
      of neural development. Studies of the Drosophila PNS have provided key insights
      into molecular mechanisms of cell fate specification, asymmetric cell division,
      and dendritic morphogenesis. A canonical lineage gives rise to sensory neurons
      and associated organs, and cells within this lineage are diversified through
      asymmetric cell divisions. Newly specified sensory neurons develop specific
      dendritic patterns, which are controlled by numerous factors including
      transcriptional regulators, interactions with neighboring neurons, and
      intracellular trafficking systems. In addition, sensory axons show modality
      specific terminations in the central nervous system, which are patterned by
      secreted ligands and their receptors expressed by sensory axons. Modality
      specific axon projections are critical for coordinated larval behaviors. We
      review the molecular basis for PNS development and address some of the instances
      in which the mechanisms and molecules identified are conserved in vertebrate
      development.

PMID- 24896661
TI  - Safety evaluation of ruxolitinib for treating myelofibrosis.
AB  - INTRODUCTION: In 2005, the JAK2 V617F mutation was identified and found to be
      highly prevalent in the 'Philadephia Chromosome-negative' Myeloproliferative
      neoplasms (MPN). This led to new diagnostic criteria for MPN in addition to the
      development of the first targeted therapy for myelofibrosis (MF), ruxolitinib .
      AREAS COVERED: Ruxolitinib was approved within 5 years of 'first-in-man' trials;
      it has been assessed in two large Phase III trials, and to date, several thousand
      patients have been prescribed this drug. This article reviews the latest data
      from the Phase III trials concerning efficacy and safety in addition to post
      authorisation data for this agent. Ruxolitinib is an extremely well-tolerated
      drug; it is associated with bruising, headaches, dizziness, anaemia and
      thrombocytopaenia. In addition, an augmented risk of infections has been
      documented. EXPERT OPINION: Ruxolitinib has radically altered the therapeutic
      landscape for MF with demonstrated advantages over standard therapy, irrespective
      of JAK2 mutational status and a signal suggesting survival benefit. Other JAK
      inhibitors are also in late stages of development, although the furthest advanced
      has just been withdrawn due to cases of encephalopathy (not documented with
      ruxolitinib). This reminds the clinical community of the need for post-marketing
      surveillance of safety for these agents. Challenges ahead are identification of
      appropriate surrogates for survival benefit and perhaps how to best use
      ruxolitinib either alone or in combination with other therapies.

PMID- 24896662
TI  - Vibrational anharmonicities and reactivity of tetrafluoroethylene.
AB  - Compared to ethylene and its nonfluorinated derivatives, C(2)F(4) is peculiar in
      many reactions. It very easily adds to radicals and prefers formation of four
      membered rings over Diels-Alder reactions. This has been rationalized by the
      preference of fluorine for carbon sp(3) hybridization, which is possible on
      opening of the double bond. Another property, the thermal dissociation of the C ?
      C bond, has been explained by the stabilization of the product (CF(2)) by back
      bonding. Here, it is attempted to correlate such properties with vibrational
      constants, in particular for C ? C stretching and twisting and for carbon
      pyramidalization. The only force constant found to be lowered compared to
      ethylene is that for trans pyramidalization (nu(8)), and CC bond softening on
      nu(8) distortion is indicated by the conspicuously large magnitude of anharmonic
      constant, x(18). Both observations can be rationalized by a valence-bond model
      that predicts a trans bent structure on weakening the CC bond. Conclusions are
      drawn about the dissociation path and peculiarities of the potential. Other
      anharmonicities, both experimental and calculated and some in (12)C(13)CF(4) and
      (13)C(2)F(4), are also discussed. In particular some strong Fermi resonances are
      identified and their effects accounted for.

PMID- 24896663
TI  - Catalytic anti-Markovnikov hydrobromination of alkynes.
AB  - We have developed the first catalytic method for anti-Markovnikov
      hydrobromination of alkynes. The reaction affords terminal E-alkenyl bromides in
      high yield and with excellent regio- and diastereoselectivity. Both aryl- and
      alkyl-substituted terminal alkynes can be used as substrates. Furthermore, the
      reaction conditions are compatible with a wide range of functional groups,
      including esters, nitriles, epoxides, aryl boronic esters, terminal alkenes,
      silyl ethers, aryl halides, and alkyl halides. A preliminary study of the
      reaction mechanism suggests that the hydrobromination reaction involves
      hydrocupration of an alkyne, followed by the bromination of the alkenyl copper
      intermediate. This study also suggests that 2-tert-butyl potassium phenoxide
      functions as a mild catalyst turnover reagent and provides a better understanding
      of the unique effectiveness of (BrCl2C)2 among brominating reagents. 

PMID- 24896665
TI  - Acid-catalyzed oxidative addition of a C-H bond to a square planar d8 iridium
      complex.
AB  - While the addition of C-H bonds to three-coordinate Ir(I) fragments is a central
      theme in the field of C-H bond activation, addition to square planar four
      coordinate complexes is far less precedented. The dearth of such reactions may be
      attributed, at least in part, to kinetic factors elucidated in seminal work by
      Hoffmann. C-H additions to square planar carbonyl complexes in particular are
      unprecedented, in contrast to the extensive chemistry of oxidative addition of
      other substrates (e.g., H2, HX) to Vaska's Complex and related species. We report
      that Bronsted acids will catalyze the addition of the alkynyl C-H bond of
      phenylacetylene to the pincer complex (PCP)Ir(CO). The reaction occurs to give
      exclusively the trans-C-H addition product. Our proposed mechanism, based on
      kinetics and DFT calculations, involves initial protonation of (PCP)Ir(CO) to
      generate a highly active five-coordinate cationic intermediate, which forms a
      phenylacetylene adduct that is then deprotonated to give product. 

PMID- 24896666
TI  - Ergosteroid derivatives from an algicolous strain of Aspergillus ustus.
AB  - One new ergosteroid derivative, isocyathisterol (1), and eight known compounds (2
      9) were isolated from the culture of an algicolous strain (cf-42) of Aspergillus
      ustus obtained from the fresh tissue of marine green alga Codium fragile. The
      structure and absolute configuration of 1 were unequivocally identified by using
      NMR and mass spectroscopic methods as well as quantum chemical calculations.
      Compound 1 exhibited weak antibacterial activity.

PMID- 24896668
TI  - Control of vocal production in budgerigars (Melopsittacus undulatus): selective
      reinforcement, call differentiation, and stimulus control.
AB  - Budgerigars were trained to make a specific call using a real-time automated call
      recognition system and food reward. Calls produced by the bird were followed by
      food only if they were similar enough to a template call. The selective
      reinforcement of a particular call type increased the similarity of the bird's
      call to the template and decreased overall call variation, including call
      duration. After the birds' performance reached asymptote (i.e. the calls became
      matched to the template with no further increase in similarity), a call
      differentiation procedure was introduced. This procedure consisted of both
      matching-to-template and non-matching-to-template trials. In order to receive
      food in non-matching-to-template trials, the birds had to produce a call that was
      sufficiently different from the template call. This procedure resulted in a 'new'
      call emerging from the first template call which occurred gradually rather than
      abruptly. In the third procedure, called two-template matching training, the
      birds had to match their calls to the first template call (signaled by
      illuminating the left LED) and to the second template call (signaled by
      illuminating the right LED). The calls produced in both first and second template
      call trials were well controlled by the position of the LED. These results extend
      the effects of selective reinforcement, differential reinforcement, and stimulus
      control on response topographies to the domain of vocalizations in budgerigars. 

PMID- 24896669
TI  - Pavlovian conditioning of sexual behavior in male threespine stickleback
      (Gasterosteus aculeatus).
AB  - This study examines whether the sexual behavior of male threespine stickleback
      (Gasterosteus aculeatus) can be conditioned using a Pavlovian conditioning
      procedure. Eight males were trained to discriminate between a red and a green
      signal where one signal (reinforced conditioned stimulus, CS+) was followed by
      the presentation of a gravid female and the other signal (nonreinforced stimulus,
      CS-) was never followed by the presentation of a female. After the training phase
      (240 trials), males were presented with extinction trials (160 trials). Males
      rapidly learned the discrimination task, performing more approaches and zigzags
      (a courtship dance) to the CS+ than to the CS- during training trials. Throughout
      the extinction phase, males continued to approach and zigzag more to the CS+ than
      to the CS-, but conditioned responses to the CS+ slowly declined over this phase.
      Learning may be an adaptive mechanism by which a male anticipates a potential
      mate, and becomes prepared to court, rather than attack, an approaching female. 

PMID- 24896667
TI  - Characterization and identification of clinically relevant microorganisms using
      rapid evaporative ionization mass spectrometry.
AB  - Rapid evaporative ionization mass spectrometry (REIMS) was investigated for its
      suitability as a general identification system for bacteria and fungi. Strains of
      28 clinically relevant bacterial species were analyzed in negative ion mode, and
      corresponding data was subjected to unsupervised and supervised multivariate
      statistical analyses. The created supervised model yielded correct cross
      validation results of 95.9%, 97.8%, and 100% on species, genus, and Gram-stain
      level, respectively. These results were not affected by the resolution of the
      mass spectral data. Blind identification tests were performed for strains
      cultured on different culture media and analyzed using different instrumental
      platforms which led to 97.8-100% correct identification. Seven different
      Escherichia coli strains were subjected to different culture conditions and were
      distinguishable with 88% accuracy. In addition, the technique proved suitable to
      distinguish five pathogenic Candida species with 98.8% accuracy without any
      further modification to the experimental workflow. These results prove that REIMS
      is sufficiently specific to serve as a culture condition-independent tool for the
      identification and characterization of microorganisms. 

PMID- 24896670
TI  - The role of hen's weight and recent experience on dyadic conflict outcome.
AB  - This study simultaneously varied experiences of recent victory or defeat, 2-h
      familiarity with the meeting place, and hen weight in order to understand their
      combined effects on the establishment of dyadic dominance relationships between
      hens not previously acquainted with each other. Three kinds of encounters were
      arranged: (i) a previous winner unfamiliar with the meeting place met a previous
      loser familiar with the meeting place (n=28 dyads); (ii) a previous winner met a
      previous loser, both unfamiliar with the meeting place (n=27); (iii) a previous
      winner familiar with the meeting place encountered a previous loser unfamiliar
      with the meeting place (n=28). The weight asymmetry was combined with these three
      types of encounters by selecting hens showing various weight differences, in
      favour of the recent loser in 54 dyads and of the recent winner in 29 dyads.
      Results indicate that recent victory or defeat experience significantly affected
      the outcome. Even an important weight asymmetry, or familiarity with the meeting
      place were not sufficient for a hen recently defeated to overcome an opponent
      that was previously victorious. A 2-h period of familiarization with the meeting
      place did not provide any significant advantage over unfamiliarity. Although a
      significant relationship was found to exist between comb and wattles areas and
      the initial and final statuses, examination of partial correlations indicates
      that the influence was from initial status to final status, rather than from comb
      and wattles to final status. These results suggest that more importance should be
      attributed to recent social experience in comparison to intrinsic factors in
      determining dyadic dominance in the hen. 

PMID- 24896671
TI  - Effects of day-length variations on emotional responses towards unfamiliarity in
      Swiss mice.
AB  - Pineal melatonin secretion occurs at night in all vertebrates and the duration of
      its secretion is negatively correlated with day length. As an anxiolytic activity
      of melatonin has been shown in rats and mice, this study examined possible
      changes of emotional reactivity in response to day length variations in Swiss
      mice. Three groups of mice were observed in a free-exploratory test: a group
      submitted to a short-day exposure (6:18 h light-dark cycle) for 2 weeks, a group
      submitted to a long-day exposure (18:6 h light-dark cycle) for 2 weeks and a
      control group which was maintained in housing 12:12 h light-dark cycle. The short
      day exposed group of mice exhibited significantly fewer attempts to enter into
      the unfamiliar enclosure, spent significantly more time in it and presented
      significantly more rears than controls whereas the long-day exposed group of mice
      made more attempts than controls. These results suggest a decreased emotional
      level in short-day exposed mice and an increased level in long-day exposed mice.
      This could be interpreted as confirming the idea of anxiolytic-like properties of
      melatonin; however, the specific role of this hormone in the changes of anxiety
      related to day length must be assessed by further measures of potential
      variations of circulating melatonin. 

PMID- 24896672
TI  - The role of recent experience and weight on hen's agonistic behaviour during
      dyadic conflict resolution.
AB  - Recent victory or defeat experiences and 2-h familiarity with the meeting place
      were combined with size differences in order to better understand their effects
      on the behaviour leading to the establishment of dyadic dominance relationships
      between hens not previously acquainted with each other. Three kinds of encounters
      were videotaped: (i) A previous winner unfamiliar with the meeting place met a
      previous loser familiar for 2 h with the meeting place (n=12 dyads); (ii) as in
      (i) but both were unfamiliar with the meeting place (n=12); (iii) as in (i) but
      the previous winner was familiar with the meeting place while the previous loser
      was unfamiliar (n=13). The weight asymmetry was combined with these three types
      of encounters by selecting hens of various weight differences: In 29 dyads the
      recent loser was heavier than the recent winner and in eight dyads it was the
      reverse. Recent experience had a major influence upon both agonistic behaviour
      and dominance outcome. Hens that were familiar with the meeting site initiated
      attacks more frequently than their unfamiliar opponent but did not win
      significantly more often. Recent experience and site familiarity could be used to
      identify 80% of future initiators. Once the first aggressive behaviour had been
      initiated, it led to victory of its initiator in 92% of cases. Weight was not
      found to influence agonistic behaviour nor dominance outcome. However, hens with
      superior comb and wattles areas won significantly more initial meetings than
      opponents with smaller ones. In the final encounters, victory also went more
      frequently to the bird showing larger comb and wattles, which happened also to be
      the previous dominant in a majority of cases. The use of higher-order partial
      correlations as an ex post facto control for comb and wattles indicates that they
      were not influential upon agonistic behaviour nor on dominance outcome, but were
      simply co-selected with the selection of victorious and defeated birds in the
      first phase of the experiment designed to let hens acquire recent victory/defeat
      experience. 

PMID- 24896673
TI  - Post-weaning social factors promote motor and social behaviors in staggerer mice.
AB  - Male staggerer mutant mice generally do not mate. This lack of spontaneous sexual
      behavior may be partially due to motor disturbances associated with cerebellar
      abnormalities. Social experience and probable sensory motor stimulation produced
      by the post-weaning cohabitation with several non-mutant mice improve the adult
      interactive behaviors of staggerer males when encountering sexually receptive non
      mutant females. Tested for their motor capacities, these experienced males
      perform better when compared to control males who cohabited with only one non
      mutant after weaning. These results correspond to the first demonstration of post
      weaning social experience effects both on motor control and on social
      interactions in the same individuals of homozygous staggerer mice. 

PMID- 24896674
TI  - Relative importance of initial individual differences, agonistic experience, and
      assessment accuracy during hierarchy formation: a simulation study.
AB  - This simulation study explores some conditions leading to transitivity within
      dominance orders. Combinations of three parameters were varied to study their
      consequences upon hierarchy formation and upon the degree of linearity of
      resultant structures. The factors studied were: (1) the importance of initial
      resource holding potentials (RHPs); (2) changes brought in RHPs by successive
      victories and defeats; and (3) accuracy of RHP assessment made by opponents.
      Results show that initial differences in RHP always lead to perfectly transitive
      chains whose rank order reflects the importance of initial differences. Even when
      simulated animals make important errors while assessing each other during round
      robin tournaments, emerging dominance structures are perfectly linear and ranks
      obtained in the structure are highly correlated with initial values in RHPs.
      Moreover, accumulated experiences of victory and/or defeat alone always lead to
      perfectly linear hierarchies. Their combination with initial individual
      differences in RHP led to the same conclusion. Even when assessment was far from
      being perfect, not only perfect chains were formed but initial values in RHPs
      significantly influenced rank order when the contribution of victory and defeat
      to RHP was relatively unimportant. The higher the importance of victory and
      defeat to RHP as compared to that of initial RHP values, the lower was the
      correlation between initial RHP values and the ranks order reached by individuals
      in the resultant hierarchies. In general also, the lower the variation within
      initial RHPs, the lower was the correlation between initial RHPs and ranks in the
      hierarchy. At a given level of initial RHP dispersion, increasing the
      contribution of victory and defeat to RHP diminished the correlation between
      initial RHP values and obtained ranks. In addition, inaccurate assessment reduced
      the overall correlation, especially when dispersion of initial RHP values was low
      and the contribution of victory and defeat relatively unimportant. These results
      shed some light on the controversy about the respective roles of initial
      individual attributes and that of patterns of resolution in the formation of
      animal hierarchies. We present the emergence of social order within closed
      systems as those simulated here as a case of self-organization. 

PMID- 24896675
TI  - A comparative study on the paths of five anura species.
AB  - The movements of five species of European toads were recorded in the daytime and
      at night in a 3*3 m area. The paths obtained were analyzed according to the first
      order correlated random walk model developed by Bovet and Benhamou with which it
      is possible to characterize each path with two independent indices: its sinuosity
      and its speed. The analysis showed that the day/night variable affected the
      sinuosity of the paths but not their mean speed. Significant differences between
      species were found to exist, however, in the case of both the sinuosity and the
      speed. It is worth noting that these interspecific behavioural differences did
      not match the classical phylogenetic classification, as shown by multiple
      comparison tests. 

PMID- 24896676
TI  - Behavioural roles and task partitioning in the primitively eusocial wasp:
      Belonogaster juncea juncea (Hymenoptera: Vespidae).
AB  - This study, conducted to examine the phenomenon of task partitioning in
      primitively eusocial insects, permitted us to record 39 behavioural items in
      colonies of the polistine wasp Belonogaster juncea juncea. Of these, 18 and 21
      items were quantified using the instantaneous scanning technique in pre-emergence
      and post-emergence phase colonies, respectively. A principal components analysis
      showed that among these items, 'absence from nest' (Afn), 'cell inspection' (Is),
      'receive prey' (Rp), 'malaxate prey' (Mp) for pre-emergence colonies, and 'cell
      inspection' (Is), 'self-grooming' (Sg), 'egg-laying' (E1), 'cell initiation'
      (CI), 'move nesting material' (Mn), 'receive prey' (Rp), 'absence from nest'
      (Afn) for post-emergence colonies, are useful for describing the individual
      variability in a given colony. Nevertheless, a hierarchical cluster analysis
      based on all behavioural items quantified showed that five main behavioural roles
      could be defined viz: Foraging, building, feeding, inactivity and reproduction.
      The items, 'land with prey' and 'feed larva' were not correlated, showing that
      there is a slight task partitioning in regard to prey handling. In both pre- and
      post-emergence colonies, the same functions are performed but, the growing number
      of individuals and the greater availability of nesting material in old cells
      modified the composition of the items associated with reproductive behaviour at
      the post-emergence stage. 

PMID- 24896678
TI  - The differential outcomes effect: A demonstration in domestic chickens responding
      under a titrating-delayed-matching-to-sample procedure.
AB  - The differential outcomes effect refers to the increase in speed of acquisition
      or terminal accuracy that occurs in discrimination training when each of two or
      more discriminative stimuli is correlated with a different outcome (e.g. type of
      reinforcer). The present study demonstrated this effect in domestic hens exposed
      to a titrating-delayed-matching-to-sample procedure, under which correct
      responses increased (and incorrect responses decreased) the delay between the
      offset of a sample stimulus and the onset of two comparison stimuli. Colors of
      key illumination (red, green) were used as sample and comparison stimuli and
      correct responses resulted in 1- or 4-s food deliveries. When 1-s food deliveries
      consistently followed correct responses to one key color and 4-s food deliveries
      followed correct responses to the other key color, the maximum delay reached by
      the hens and their overall accuracy was significantly higher than when 1- and 4-s
      food deliveries were randomly arranged following correct responses to both key
      colors. These data constitute the first demonstration of the differential
      outcomes effect in chickens, and in any species evaluated under a titrating
      delayed-matching-to-sample procedure. 

PMID- 24896677
TI  - Triplet excited state energies and phosphorescence spectra of
      (bacterio)chlorophylls.
AB  - (Bacterio)Chlorophyll ((B)Chl) molecules play a major role in photosynthetic
      light-harvesting proteins, and the knowledge of their triplet state energies is
      essential to understand the mechanisms of photodamage and photoprotection, as the
      triplet excitation energy of (B)Chl molecules can readily generate highly
      reactive singlet oxygen. The triplet state energies of 10 natural chlorophyll
      (Chl a, b, c2, d) and bacteriochlorophyll (BChl a, b, c, d, e, g) molecules and
      one bacteriopheophytin (BPheo g) have been directly determined via their
      phosphorescence spectra. Phosphorescence of four molecules (Chl c2, BChl e and g,
      BPheo g) was characterized for the first time. Additionally, the relative
      phosphorescence to fluorescence quantum yield for each molecule was determined.
      The measurements were performed at 77K using solvents providing a six-coordinate
      environment of the Mg(2+) ion, which allows direct comparison of these (B)Chls.
      Density functional calculations of the triplet state energies show good
      correlation with the experimentally determined energies. The correlation
      determined computationally was used to predict the triplet energies of three
      additional (B)Chl molecules: Chl c1, Chl f, and BChl f. 

PMID- 24896680
TI  - Formalin pain does not modify food-hoarding behaviour in male rats.
AB  - Many animal species hoard food by carrying it to their home area. In this
      experiment we evaluated the interaction between persistent (formalin) pain and
      food-hoarding behaviour. A food-hoarding apparatus, consisting of a home cage
      connected with an alley at the end of which were placed food pellets, was used to
      test (60 min each day) food-restricted rats which had been familiarized with the
      apparatus for three days. Three groups of animals were used, one of which was
      tested in the apparatus in the absence of pellets. On the day of testing, the two
      groups of rats allowed to perform food-hoarding were either sham- or formalin
      injected (50 MUl, 10%) in the dorsal surface of the hind paw immediately before
      testing; the third group, not allowed to hoard pellets, was also injected with
      formalin. In animals treated with formalin, the availability of food resulted in
      shorter durations of Licking, Self-Grooming and Inactivity. In animals allowed to
      hoard food, formalin injection affected neither hoarding parameters nor
      exploratory activities. Our results show that, in food-restricted rats, food
      hoarding behaviour is not modified by persistent nociceptive stimuli while
      Licking, a complex response to formalin pain, is decreased by the drive to
      relieve hunger. 

PMID- 24896679
TI  - Social discrimination in Japanese quail Coturnix japonica chicks genetically
      selected for low or high social reinstatement motivation.
AB  - Japanese quail chicks of two lines genetically selected for low levels of social
      reinstatement behaviour (LSR) or high levels of social reinstatement behaviour
      (HSR) were housed in groups of three. The approach/avoidance tendencies of an
      individual chick from each group towards a familiar cagemate and a stranger from
      another group placed at opposite ends of a runway were measured at 7 days of age.
      Quail chicks of both genetic lines preferentially approached, spent longer near,
      and showed shorter mean distances from the cagemate than the stranger.
      Irrespective of stimulus type, the HSR quail generally showed shorter approach
      latencies, spent longer within 15 cm of the goal boxes, made more entries into
      these areas, and travelled further during the test than did their LSR
      counterparts. These findings demonstrated that Japanese quail chicks, of two
      genetic lines reared in small groups, successfully discriminated between familiar
      cagemates and strangers. They also suggest that there are no straightforward
      relationships between underlying social motivation and social preferences. 

PMID- 24896681
TI  - Socialization processes in primates: Use of multivariate analyses. I: Application
      to social development of captive mangabeys.
AB  - We hypothesized that, within a primate group, socialization processes are
      influenced by each group member behaving according to his own social network.
      Therefore socialization processes would differ in various social environments. In
      this study, we considered two main socialization processes, the acquisition of a
      social behavioral repertoire and the development of a network of social
      relationships, and consequently defined six comprehensive developmental
      parameters. We analyzed the variability of these parameters using a new
      multifactorial method, the Principal Components Analysis with Instrumental
      Variable, PCAIV, derived from the Principal Components Analysis and Multivariate
      Analyses of Variance. This technique allowed us to jointly represent the
      influence of the independent variables and the complex relationships between the
      six dependent variables. The study of the social ontogeny of eight infant
      mangabeys (Cercocebus albigena), reared in three different social environments,
      served as an illustration of the use of the new multivariate analysis. A 3
      variable-model (age, social environment and sex) significantly explained the
      variability of the developmental parameters. The results confirmed the importance
      of social interactions in non-human primate infants' development. The application
      of multivariate methods to the study of individual social development looks
      promising for future research. 

PMID- 24896682
TI  - Astronomical orientation and learning in the earwig Labidura riparia.
AB  - Astronomical orientation experiments have been carried out on adults and young of
      the earwig Labidura riparia. In the water, the earwigs. 

PMID- 24896683
TI  - Conditioned inhibition of social approach in male Japanese quail (Coturnix
      japonica) using visual exposure to a female.
AB  - Male Japanese quail (Coturnix japonica) learned to approach lights that predicted
      visual exposure to a female quail and showed significantly less approach to
      lights that predicted the absence of a female quail. Following discrimination
      training, subjects were given transfer summation tests in which a stimulus
      positively correlated with female exposure (CS +) was presented alone,
      simultaneously with a novel stimulus, and simultaneously with a stimulus
      negatively correlated with female exposure (CS -). Approach to the CS + was lower
      when the CS + and CS - were presented together than when the CS + was presented
      alone or when the CS + was presented with a novel stimulus. These findings
      demonstrate conditioned inhibition of sexual conditioned approach in Japanese
      quail. 

PMID- 24896684
TI  - Demand for nest boxes in laying hens.
AB  - Domestic hens (Gallus gallus domesticus) from commercial laying strains have been
      selected for high egg yield and may lay over 300 eggs in their working lives. In
      conventional wire cages, there is little opportunity to perform either nest
      seeking or nest building activities, which may lead to frustration each time an
      egg is laid. To measure the demand for a well-defined nest-site, which may act as
      a consummatory stimulus for nest seeking behaviour and an appetitive stimulus for
      nest building behaviour, 16 hens were allowed to work to gain access to a pen
      containing two littered, enclosed nest boxes. The cost of access to the nest
      boxes was varied by changing the width of the vertical gap, which divided a home
      pen containing food, water and a perch from the pen containing the nest boxes
      (gaps of 220, 140, 125, 110 and 95 mm, compared with mean body width of 117 mm).
      The number of entries to the nest pen declined with narrowing gap, whilst the
      number of failed attempts to enter rose, but all 16 hens persevered with entering
      the nest pen prior to oviposition and laid in the nest boxes. Between 120 and 30
      min to oviposition hens made many entries with the 220 mm gap (27.6), but this
      declined to no entries with 95 mm gap. Hens made few entries in the last half
      hour prior to ovipositoin (1.3) but there was no significant decline in entries
      as the gap narrowed (1.1 with 95 mm gap). The number of nest inspections and nest
      entries also declined with width of gap, but there was no effect on time spent in
      the nest boxes. Hens passed gaps of 220, and 140 mm to return to the nest pen
      following oviposition, but did not pass gaps of 125, 110 or 95 mm. We therefore
      conclude that the narrow gap width can be used to assess the demand for
      environmental requirements. Hens were willing to pay a high cost to gain access
      to a nest box prior to oviposition, so prelaying behaviour may be frustrated in
      hens without a well-defined, littered nest site. 

PMID- 24896685
TI  - Differences in vibratory sound communication between a Slovenian and an
      Australian population of Nezara viridula (L.) (Heteroptera: Pentatomidae).
AB  - Sound communication, by means of substrate-borne vibrations, was recorded and
      analysed from a Slovenian and Australian population of the pentatomid landbug,
      Nezara viridula. Mate location and short-range courtship in N. viridula involves
      the recognition of such species-specific signals and responding appropriately to
      them. Temporal parameters of all N. viridula song types differed considerably
      between males and females of the two populations. In particular, the female
      calling song, which enables Slovenian male bugs to locate the female on a host
      plant, was significantly different. The song repertoire from a Slovenian and
      Australian population and the species status of N. viridula are discussed. 

PMID- 24896686
TI  - Cortical differentiation and neurocognitive development: The parcellation
      conjecture.
AB  - This paper reviews evidence consistent with the Parcellation Conjecture. Briefly,
      this conjecture states that in postnatal development cortical parcellation
      processes result in previously combined information processing pathways or
      structures becoming segregated into relatively isolated modules. Evidence
      consistent with the parcellation conjecture from several aspects of behavioral
      development are reviewed, including the development of binocular vision, cross
      modal integration, and interhemispheric transfer. Predictions are made in other
      domains where existing evidence is unclear such as motion and color sensitivity,
      and somatosensory perception. Finally, we speculatively extend the notion of
      parcellation to more cognitive domains such as the development of priming and
      interference effects. 

PMID- 24896687
TI  - Towards highly efficient photoanodes: boosting sunlight-driven semiconductor
      nanomaterials for water oxidation.
AB  - Harvesting energy directly from sunlight is a very attractive and desirable way
      to solve the rising energy demand. In the past few decades, considerable efforts
      have been focused on identifying appropriate materials and devices that can
      utilize solar energy to produce chemical fuels. Among these, one of the most
      promising options is the construction of a photoelectrochemical (PEC) cell that
      can produce hydrogen fuel or oxygen from water. Significant advancement in the
      understanding and construction of efficient photoanodes to improve performance
      has been accomplished within a short period of time owing to various newly
      developed ideas and approaches, including facilitating charge transportation in
      narrow band gap semiconductors or doping in wide band gap semiconductors for
      enhancing visible-light absorption; electrocatalysts for decreasing
      overpotentials; controlling the morphology of the materials for enhancing light
      absorption and shortening the transfer distance of minority carriers; and other
      methods such as using heterojunction structures for band-structure engineering,
      sensitization, and passivating layers. In this review, we focus on the recent
      developments of some promising visible-light active photoanode materials with
      high PEC performance, such as BiVO4, alpha-Fe2O3, WO3, TaON, and Ta3N5. 

PMID- 24896688
TI  - Behavioural and nociceptive response in male and female spiny mice
      (Acomyscahirinus) upon exposure to snake odour.
AB  - Predator cues (both mammalian odour or avian vocalizations) are known to elicit
      fear-associated responses in rodents, including analgesia. In previous studies it
      was reported that spiny mice fail to show fear responses when presented with the
      calls of an owl. In order to test the hypothesis that this species (living in
      semiarid and rocky areas) may react to stimuli coming from reptilian predators,
      40 sexually mature spiny mice (20 males, 20 females) were individually exposed to
      a small cylinder containing either fresh sawdust or snake odour. Behavioural
      changes (5 min before and 15 min after odour exposure) as well as the subsequent
      performance in a hot-plate test (50+/-0.5 degrees C) were assessed. Results
      indicate that exposure to the odour of a sympatric terrestrial predator affected
      both behavioural and physiological responses of spiny mice. Upon exposure to
      snake odour both sexes showed significant changes in the patterns of inactivity,
      sniffing, grooming, sniffing the stimulus object (SO), withdraw reaction and in
      the frequency of somersaults. However, males increased the frequency of rearing,
      sniffing the SO, decreasing grooming more than females. No analgesic effect of
      odour exposure emerged; however, males showed significantly shorter latencies and
      higher frequencies of hindpaw licking compared to females. 

PMID- 24896689
TI  - Time budget as related to feeding tactics of European polecat Mustela putorius.
AB  - The time budget of five male and four female European polecats was studied in
      western France through radiotracking surveys. Their activity level averaged 7 h
      and 31 min without any significant differences between males and females. However
      two phases, foraging and travelling, were not similarly distributed in both
      sexes. Despite a strong sexual dimorphism, females spent more time foraging than
      males. Travelling, i.e. time devoted to linear movements was more important in
      males than females. Variations in activity phase duration were correlated with
      the proportions of food categories, suggesting that the dispersion of available
      resources directly influenced polecat activity. The exploitation of prey showing
      an aggregative distribution such as anurans led to a decrease in general activity
      whereas the consumption of rodents, which were more regularly distributed, was
      correlated to the foraging activity. Mating and breeding also affected the
      activity duration. Thus it seems that the time budget of polecats resulted from a
      compromise between social organization and trophic constraints. 

PMID- 24896690
TI  - Do ewes recognize their lambs within the first day postpartum without the help of
      olfactory cues?
AB  - Two studies were carried out to test the ability of Prealpes du Sud x Lacaune
      (Study 1) and Rambouillet ewes (Study 2) to recognize their lambs during the
      first 24 h postpartum. Ewes were given the choice between their own and an alien
      lamb of approximately the same age, in a triangular pen of 10 m*10 m*10 m. A lamb
      was placed in each of the two corners while the mother was released from the
      third corner. Direct access to the lambs was prevented by an open barrier located
      at 1 m from the pens in which the lambs were kept. Ewes were studied at 8 h
      (n=10, 12), 12 h (n=20, 10) and 24 h postpartum (n=29, 9; Study 1 and Study 2
      respectively). Tests lasted 3 and 5 min in Study 1 and 2, respectively. Although
      the first choice of the ewes did not differ from random, in both studies mothers
      spent significantly more time near their own lamb than near the alien. In both
      breeds a significant preference for the own lamb was already present at 8 h
      (P<0.05). We conclude that ewes are very likely to recognize their lamb without
      the aid of olfactory cues as early as 8 h postpartum, which is much sooner than
      thought from previous studies. 

PMID- 24896691
TI  - The McCollough effect in pigeons: tests of persistence and spatial-frequency
      specificity.
AB  - Eight pigeons were trained on a conditional discrimination using red and green
      saturated and desaturated fields, and red and green saturated and desaturated
      vertical and horizontal black-on-colour gratings. The pigeons learned to
      discriminate the stimuli on the basis of colour, to a high level of accuracy,
      regardless of saturation or the presence of gratings. The pigeons were then
      repeatedly exposed to stimuli in which colour and grating orientation were
      correlated, following which they were tested for the presence of the McCollough
      orientation-contingent colour after-effect, using black-on-white vertical and
      horizontal gratings. Six of the birds showed convincing evidence of the presence
      of the McCollough effect, and the effect was significant across all birds. These
      findings support those of Roberts (1984), using a substantially different
      methodology. The six birds showing the McCollough effect were then tested for the
      persistence of the effect at delays of 24 to 96 h. Four of the birds showed
      evidence of the McCollough effect at least 24 h after the induction procedure.
      Three of these birds were also tested to investigate the spatial frequency
      selectivity of the effect. The results suggest a narrow tuning of the McCollough
      effect in pigeons of less than 0.36 log units. 

PMID- 24896692
TI  - Do young guinea pigs (Cavia porcellus) develop an attachment to inanimate
      objects?
AB  - Filial imprinting has been studied extensively in precocial birds. In these
      studies, inanimate objects were used as imprinting objects. Although attachment
      to the parents is common in mammals, experiments with inanimate objects are rare
      and mostly restricted to guinea pigs (Cavia porcellus). The results of these
      studies are inconclusive. The aim of the present experiment was to assess whether
      guinea pigs can develop an attachment to inanimate objects. For this purpose, 11
      young guinea pig pups were taken from their mothers within 16 h after birth, and
      subsequently reared individually in the presence of an inanimate object. Between
      2 and 35 days of age, the pups were submitted to preference tests as well as
      separation tests. Neither test provided evidence of attachment: during
      separation, the pups did not increase their distress calling; moreover, pups
      preferred a novel object to their rearing object in the preference tests. 

PMID- 24896693
TI  - Discriminative stimulus properties of music in Java sparrows.
AB  - Seven adult Java sparrows were trained to discriminate music by Bach and that by
      Schoenberg. In the Bach S+ group perching response was reinforced when piano
      music by Bach was played but not when piano music by Schoenberg played. The
      Schoenberg S+ group received reversed training. Five of seven birds reached the
      criterion. Novel orchestra music by Bach and that by Schoenberg were played in
      the first test after the discriminative training. They showed generalization to
      new music by Bach and Schoenberg. When Vivaldi and Carter were played in the
      second test, all five birds showed significant discrimination. Bach S+ group
      responded to Vivaldi and Schoenberg S+ group responded to Carter. Vivaldi and
      Bach belonged to the same category, namely classical music, while Carter belongs
      to the modern music properties common to humans and birds. 

PMID- 24896694
TI  - Temporal threshold and response bias in the discrimination of empty intervals by
      cats.
AB  - Cat's differential duration threshold was investigated by the method of limits in
      a schedule of discrimination of empty durations. The standard stimulus was 4 sec
      long throughout the experiment. The comparison stimulus was reduced from 10 to 5
      sec by 1 sec steps in successive blocks of 5 sessions. Standard and comparison
      stimuli, delimited by 50 msec auditory signals, were equiprobably distributed, in
      a random sequential order of presentation in each trial. After a 2 sec delay, an
      auditory signal indicated that reinforcement was available upon a response on one
      of two levers. Weber fractions around .25 were obtained. Strong response bias
      developed in most cats. Some consequences of the inhibition of responding induced
      by the procedure were considered. 

PMID- 24896695
TI  - A probabilistic model of the spatial patterning of pecking in birds : Pilot study
      with young chicks.
AB  - The pecking behaviour of young chicks (Gallus gallus ) is studied in a situation
      involving several equivalent targets (mealworms). The question is raised whether
      the successive pecks are randomly distributed or whether they follow a systematic
      order based on the spatial arrangement of the targets. Data collected with one
      week-old chicks indicate that pecking is compatible with a probabilistic model
      where the probability to peck at a given place is inversely proportional to the
      energy used for this particular peck. Pecking by chicks is interpreted as a
      functional compromise between random sampling and optimal exploitation of the
      environment. 

PMID- 24896696
TI  - An illustration of simple sequence analysis with reference to the agonistic
      behaviour of four strains of laboratory mouse.
AB  - Many authors have assumed that the functions of behavioural elements may be
      deduced from the sequence in which they occur. This study explains from basic
      principles a simple procedure, based of the X(2) test, for analysing behavioural
      sequences. The formation of groups of "similar" elements (cluster analysis) and
      their interpretation is discussed with reference to the agonistic behaviour of
      individually-housed male mice from four different strains. Associations between
      elements are found to be consistent with the functions assigned them by previous
      authors though strain differences in behavioural organisation are evident. Behav.
      Processes 11: 365-388. 

PMID- 24896697
TI  - Resistance to variable-time schedules produced by spaced-response reinforcement
      schedules.
AB  - Two experiments are reported in which rats were exposed to either a tandem fixed
      ratio 1 differential-reinforcement-of-low-rate 10 sec schedule (tand FR1 DRL 10)
      (Experiment 1) or to a DRL 10 sec schedule (Experiment 2) prior to being exposed
      to a variable-time (VT) schedule. Response decrement was not universally found
      during the VT phase, one rat emmitting an increase in response rate relative to
      baseline (Experiment 1), while another showed neither an increase nor decrease
      during VT relative to baseline (Experiment2). The VT schedule induced less
      efficient responding in both experiments. Interresponse time (IRT) distributions
      (Experiment 2) indicated that the VT changed the pattern of responding. These
      results, when combined with others from our laboratory, indicate that although
      unsignalled variable delay of reinforcement may be a sufficient condition for
      producing resistance to response-independent reinforcement, it is not a necessary
      condition. It was concluded that a response competition model of the kind
      proposed by Henton and Iversen (1978) might have explanatory merit in this kind
      of experimental situation. 

PMID- 24896698
TI  - Social facilitation in a troop of Guinea Baboons (Papio papio) living in an
      enclosure.
AB  - A method is described of assessing whether or not social facilitation occurred in
      a troop of Guinea Baboons (Papio papio) living in an enclosure. The method did
      not involve the removal of individuals from the troop. The study revealed an
      interaction between social facilitation and the quality of social relationship
      involved; affiliative relationships enhanced the social facilitation of leaving
      an experimental zone. The theoretical implications of this finding are discussed.
      The method also disclosed an anomaly of learning in a group: making mistakes
      during reversals of a discrimination problem was also subject to social
      facilitation. This finding corroborates Zajonc's report (1967) of several results
      on social facilitation of errors. 

PMID- 24896699
TI  - Mate choice and male behaviour following castration and replacement of
      testosterone in mallards (Anas platyrhynchos ).
AB  - Male sexual behaviour was controlled by castration and testosterone replacement.
      The first experiment shows that, within a group of similarly coloured and
      castrated male mallards, females preferred males treated with testosterone. The
      second experiment shows that a testosterone-treated male was always preferred by
      the females, irrespective of plumage colour, in a choice between a wild and a
      white mallard drake. The results shows that testosterone dependent male cues is
      important in mate choice in the mallard duck. 

PMID- 24896700
TI  - Polyethism in social interactions in ants.
AB  - Worker ants, which perform various tasks in their society (division of labour or
      polyethism), also demonstrate different types of antennal activity in
      trophallactic interactions. These differences concern the variability in
      successions of behavioural units performed by the worker in the course of
      substance transmission as well as in the sequential organization of these units.
      The antennal activity of an aged worker varies according to whether the ant gives
      food to another aged worker or to a callow worker. In the latter case, the
      donor's behaviour does not differ according to its social function (brood-tending
      worker or forager). A parallel can be established between these results and those
      obtained in a previous study of aggressive behaviour. This behaviour is liable to
      appear when a callow worker extracted from its society before hatching and
      therefore deprived of relations with aged workers of the society, is therefore
      placed with an aged worker. Polyethism is then manifested in social interactions,
      and not only in the division of labour between members of the society. 

PMID- 24896701
TI  - The effects of mate separation on pair re-formation in the Texas cichlid fish
      (Cichlasoma cyanoguttatum ).
AB  - This study tested whether mated pairs of Texas cichlid (Cichlasoma cyanoquttatum
      ) would reform and continue rearing their offspring after being separated for
      either one, four, or ten days. All pairs successfully re-formed after one day,
      while only 50% re-formed after 4 days. No pair re-formed after 10 days of
      separation. In successfully re-formed pairs, the female was always more
      aggressive than her mate, irrespective of whether the female was the resident or
      the returning individual. Aggressiveness seemed related to the female's attempt
      to control the male's parental behavior. For pairs which did not re-form, the
      resident parent, either the male or female, violently and continously attacked
      the returned mate. 

PMID- 24896706
TI  - Object retrieval by Norway rats as a framework for preference and choice.
AB  - Object retrieval by Norway rats consists of locomotion to an object, object
      seizure, carriage to a refuge and release. These studies examined choices in this
      sequence and object preferences (relative numbers retrieved) for objects varying
      in sweetness. In Experiment 1, rats could retrieve two types of object on each
      trial, drawn from a set of three, each placed in quantity in one arm of a Y-maze
      connected to the home cage. After a period of learning, a stable preference
      hierarchy was demonstrated that depended on choices in different parts of the
      retrieval sequence i.e. decision making was broadly distributed. For the middle
      object in the hierarchy, response probabilities varied with object pairing,
      suggesting that rats responded in terms of object-sets. Preferences also involved
      rapid updating at the beginning of each trial (working memory) manifested in
      shifts in responding in all segments that supported consistent choices.
      Experiments 2-3, with an empty arm as an extra alternative, indicated that visits
      to an arm with less-preferred objects represented exploration interspersed with
      retrieval. Preference and choice are fundamental to object retrieval in this
      species and choice consistency in a dynamic environment is based on learning and
      memory. 

PMID- 24896707
TI  - The missing link between neurobiology and behavior in Aplysia conditioning.
AB  - Over the past decades, a wealth of findings has led to a substantial change in
      the assumed complexity of classical conditioning. The combined evidence indicates
      that temporal pairing is neither necessary nor sufficient for the formation of an
      associative connection. At the same time, studies of model invertebrate nervous
      systems have allowed us to ask a series of questions about the molecular basis of
      associative conditioning. The discovery of a pairing-sensitive mechanism in the
      gill-withdrawal circuitry of Aplysia is regarded as the hallmark of the
      reductionist approach. This review outlines the insights gathered from behavioral
      and neurobiological studies. Furthermore, the conceptual frameworks guiding
      research at the 'what' and 'how' levels of analysis are compared and contrasted.
      I argue that a rich cognitive view of conditioning has emerged at the 'what'
      level, whereas the traditional notion of temporal pairing still drives research
      at the 'how' level. A complete account of classical conditioning has to await the
      resolving of this discordance. 

PMID- 24896708
TI  - Rat toys, reinforcers, and response strength: An examination of the Re parameter
      in Herrnstein's equation.
AB  - The response-strength equation is a mathematical model used to explain responding
      on variable-interval (VI) schedules. This equation has two fitted parameters, k
      and Re. Empirical research suggests that k is a measure of motor performance and
      Re is a measure of background sources of reinforcement relative to the arranged
      reinforcer. This experiment examined the interpretation of the Re parameter by
      augmenting the background reinforcement with a qualitatively different source of
      background reinforcement. Rats were food deprived and received sucrose solution
      for lever responding. Each experimental session consisted of a series of seven VI
      schedules, providing reinforcement rates that varied between 20 to 1200 h(-1).
      Occasionally, cardboard tubes were introduced into the experimental chambers in
      order to provide the rats with another source of reinforcement distinct from the
      lever-response specific sucrose reinforcer. The k parameter did not change
      systematically as a result of the experimental manipulations, but Re was
      significantly larger when tubes were introduced into the chambers. These results
      are consistent with the interpretation that k and Re measure two independent and
      experimentally distinguishable parameters and that Re is a measure of
      reinforcement of background sources to the arranged reinforcer. 

PMID- 24896709
TI  - Olfaction in utero: Behavioral studies of the mouse fetus.
AB  - On the day before birth, mouse fetuses were tested for their behavioral responses
      to iso-amyl acetate and iso-valeric acid delivered into the nasal cavity in
      liquid phase. Pilot studies established that most subjects responded to most
      concentrations used with an increase in total behaviors and number of different
      behaviors displayed. When iso-amyl acetate was systematically delivered at three
      concentrations (10(-3) M, 10(-4) M and 10(-5) M) subjects showed significant
      responses to each. In contrast, responses were not evident when saline was the
      stimulus. The magnitude of the average behavioral response did not decline with
      decreasing concentration of odorant. In a second experiment, the ability of the
      fetus to discriminate between iso-amyl acetate and iso-valeric acid was studied.
      Results establish that the fetuses responded differently to the two odorants.
      Given the immaturity of the mouse's accessory olfactory system before birth and
      the observed responses to concentrations of odorants below the threshold of the
      trigeminal system, the results suggest that the mouse fetus has a functionally
      competent main olfactory system including the ability to discriminate between
      purified odorants. The results are discussed in terms of current models of
      chemosensory ontogeny. 

PMID- 24896710
TI  - The effect of context change upon long-term memory of CS duration.
AB  - An experiment with rats investigated forgetting of inhibition of delay in the
      conditioned suppression paradigm. The combined effects of contextual change and
      retention interval were tested. After a reliable temporal discrimination was
      reached, half of the rats received a test in the training context after a
      retention interval of 3 or 20 days. The other half received it in a different but
      equally familiar context at either retention interval. The longest retention
      interval flattened the temporal discrimination gradient and increased suppression
      to the CS. A similar but weaker pattern was found with the change of context;
      this effect was independent of the retention interval. The implications for
      retrieval and interference theory [Bouton, M.E., 1993. Psychol. Bull., 114: 80
      99] and hypotheses concerning the forgetting of specific features of stimuli over
      time [Riccio, D.C., Richardson, R. and Ebner, D.L., 1984. Psychol. Bull., 96: 152
      165] are discussed. 

PMID- 24896711
TI  - Reaction to conspecific degraded song by the wren Troglodytes troglodytes:
      Territorial response and choice of song post.
AB  - We investigated the response of the wren Troglodytes troglodytes to playback of a
      territorial song degraded by long-range propagation. It appears that the wren is
      sensitive to this degradation since the territorial reaction is less intense with
      the degraded song than with the undegraded one. However, the degraded song is
      still considered by the receiver as a specific territorial aggressive signal.
      This differential response suggests that the male wren can use the degradation
      characteristics of the signal to adapt its territorial reaction. Indeed, in
      response to this stimulus, the receiver wren chooses a higher song post. By so
      doing, the bird improves both the propagation distance of the emitted song and
      the receiver's ability to hear the opponent's song. This behavioural change may
      correspond to a communication strategy, counteracting the environmental
      constraints on sound propagation. Therefore, in response to sound degradation
      during long-range propagation, birds may have developed behavioural adaptations
      complementary to the various adaptations concerning song structure and coding
      decoding processes. 

PMID- 24896712
TI  - Functional groups in the social behavior of a cichlid fish, the Oscar, Astronotus
      ocellatus.
AB  - Dummy conspecifics were presented to isolated adults of the cichlid fish
      Astronotus ocellatus to investigate the functional organization of cichlid social
      behavior. Body size and 15 dummy-elicited activities were recorded during 15 min
      sessions and analyzed by principal components analysis (PCA) to reveal their
      temporal organization. Five principal components explained almost 80% of the
      variation in dummy-elicited behavior, and these five factors define functional
      groups for Nest-oriented and attack modal action patterns are not mutually
      inhibitory during this time frame, and biting does not appear to function
      exclusively during an attack on a conspecific. Comparison with previous studies
      of New and Old World cichlids suggests evolutionary conservation of the
      functional organization of social behavior. 

PMID- 24896713
TI  - Pigeon transitive inference: Tests of simple accounts of a complex performance.
AB  - This study addressed pigeons' abilities to form transitive inferences and the
      mechanism by which they do so. Subjects were trained on four operant
      discriminations in a 5-term series-A + B - , B + C - , C + D - and D + E - (where
      [ + ] denotes reward, and [ -] non-reward in choice). In unreinforced tests,
      choice of B over D is evidence of transitive inference formation. Training
      proceeded without the subjects being presented the training pairs in blocks.
      Results show that randomized training degrades the performance of pigeons, just
      as it does human subjects, but that some subjects can still respond transitively
      under these conditions. In addition, the results support reinforcement models of
      transitive inference performance. 

PMID- 24896714
TI  - Testosterone binding sites in the brain, plasma sex hormones and reproductive
      behaviour in males of the toad Bufo bufo.
AB  - The central action of steroid hormones of the regulation of reproductive
      behaviour has been recognized in Amphibia, as in, other Vertebrates. Central and
      peripheral endocrine aspects of reproductive behaviour were studied in the toad
      Bufo bufo during the breeding aspects of reproductive behaviour were studied in
      the toad Bufo bufo during the breeding (DHT) and estradiol (E) levels. In the
      first experiment the effect of early and late entrance into the breeding pond and
      the difference between animals entering and leaving was established: DHT and E
      plasma levels, as well as T binding capacity in the brain were lower in animals
      leaving the pond at the end of the breeding season; animals entering early in the
      season showed higher levels of E than those entering late. In the second
      experiment the hormonal effect of amplexus and spawning was established: single
      males showed lower plasma DHT, higher plasma E and higher T binding values in the
      brain than males paired with a female. Males in amplexus with a non-spawning
      female showed higher plasma E levels than those with a spawning female. These
      results show that it is possible to relate the different reproductive success to
      different T binding in the brain. The effect of amplexus on potential
      responsiveness to steroid hormones at the central level and on peripheral hormone
      concentrations suggests the presence of a regulatory mechanism which is more
      active when both amplexus and spawning occur. On the other hand, the data
      concerning animals entering and leaving the pond indicate that the hormonal
      variations are not due solely to the end of sexual behaviour since the difference
      is already significant between groups entering early and late in the breeding
      season. 

PMID- 24896715
TI  - Learning variable and stereotypical sequences of responses: Some data and a new
      model.
AB  - In a left-right (L-R) choice situation, pigeons were exposed to a frequency
      dependent schedule that selectively reinforced either the momentarily least
      frequent pairs of responses (Experiment 1), or the least-frequent triplets of
      responses (Experiment 2). In Experiment 1, the birds developed various
      stereotypical response patterns including double alternation (i.e. RRLLRRLL...),
      the stable pattern that satisfied the schedule constraint. In Experiment 2, three
      out of four birds developed random-like behavior. A linear operator reinforcement
      model, in the tradition of Bush and Mosteller, accounted for the qualitative
      features of pigeons' behavior in frequency-dependent schedules: strict
      alternation (i.e. RLRL...) when the schedule selectively reinforces the least
      frequent individual response, double alternation when the least-frequent pairs
      are selectively reinforced, random-like behavior when the least-frequent triplets
      are selectively reinforced, and various stereotypical response patterns
      apparently not related to the target of selection. 

PMID- 24896716
TI  - Home-range marking and territorial marking in Cataglyphis cursor (hymenoptera,
      formicidae).
AB  - According to the marking activity and to the behaviour of ants, two areas can be
      distinguished outside the nests of Cataglyphis cursor. One is the vicinity of the
      nests, near the nest entrance. Here, the ground is covered with many hindgut
      spots, and resident ants aggress alien ones in 50% of their encountering. The
      vicinity of the nests can thus be considered as being territorially marked.
      Elsewhere the foraging area is covered with only few hindgut spots, and resident
      ants are not aggressive towards alien ones. The marking of this area is species-
      rather than colony-specific and can be considered to be a home-range marking. It
      was set up progressively in about two hours in our laboratory conditions, by the
      first foragers crossing the area, and was regularly maintained thereafter.
      Experiments revealed that the hindgut may play a part in C. cursor territorial
      marking, and that the outside workers' Dufour gland may allow the specific home
      range marking. The poison gland probably interferes with the alarm-defence system
      of the species. The organ content of the young workers is inefficient, or at
      least less efficient, than that of older nestmates. This result points out the
      existence of some age-related physiological changes in the workers. 

PMID- 24896718
TI  - Female aggression during gestation and lactation in two strains of mice selected
      for isolation-induced intermale aggression.
AB  - The present study investigated whether maternal aggression is related to male
      behaviour in two strains of mice selected for isolation-induced intermale
      aggression. The strains were selectively bred from an outbred Swiss albino stock
      for high (Turku Aggressive, TA) and low (Turku Non-Aggressive, TNA) levels of
      aggression in forty-seven generations. One hundred and forty individually housed
      TA and TNA females were administered a seven-minute aggression test involving
      adult male intruders. The aggression tests were performed on day nine and
      eighteen during the gestation period, and on day one, three, six, nine and twelve
      postpartum. Separate groups of animals were tested on each of these days.
      Maternal aggression was found to be related to intermale aggression in the
      selectively bred TA and TNA strains. During the gestation period the females of
      the two lines displayed differences only with regard to sniffing, whereas during
      lactation significant differences were observed in this regard, as well as in
      attacking and tail rattling. The aggressive behaviour of the TA females reached a
      peak on day three and nine postpartum. 

PMID- 24896717
TI  - Sound avoidance by hens.
AB  - The study attempted to assess the aversiveness of various sounds by allowing six
      hens to move to one (or other) end of a chamber to turn a sound off. A number of
      sounds at varying intensities were used, including intermittent and constant pure
      tones and a number of taped sounds. Sounds which some hens moved to turn off were
      high intensity tones (105-110 decibles measured on the A scale (dB(A))), and a
      number of taped sounds, both animal and machine generated, at 90 dB(A). The
      technique appears to be reliable in producing avoidance by individual subjects,
      and it resulted in differential responding to different intensities of the same
      sound. It seems likely that spending high percentages of the time with a sound
      off in this procedure indicates that the sound is aversive. Failure to turn a
      sound off does not, however, necessarily indicate non-aversiveness. 

PMID- 24896719
TI  - Spatial discrimination learning in rats as an animal model of cognitive ageing.
AB  - Spatial discrimination learning and memory in the rat seems to be a valid animal
      model for age differences in human cognitive functioning. Inherent to these
      models are problems concerning the validity of the task and the possible
      confounding effect of the measures by age differences in non-mnemonic factors
      such as motor performance, motivation and problem-solving strategies. We have
      used different tasks such as the holeboard, the conefield and the Morris water
      escape task to evaluate spatial discrimination learning in rats of different
      ages. In the conefield task, we unexpectedly found that old Lewis rats performed
      better than young Lewis rats on the measure spatial reference memory. In
      contrast, the performance of old Lewis rats was markedly impaired in the Morris
      water- escape task compared to that of young Lewis rats. We suggest that the
      difference in outcome of these two studies is related to confounding variables
      which have distinct effects in young and old rats. The consequences of these
      findings for the use of spatial discrimination tasks as an animal model of
      cognitive ageing are discussed. 

PMID- 24896720
TI  - Multi-odour memory influenced by learning order.
AB  - Behavioural responses to odours delivered in an olfactometer prove that
      Leptopilina boulardi (Hymenoptera: Eucoilidae), a parasitic wasp of Drosophila
      larvae, is able to memorize three different odours which have been associated
      successively with oviposition experience. They exhibit differential responses
      which depend on the order of learning and also on the nature of the odours
      because an experience with one odour can influence the insect's response to
      another one. 

PMID- 24896721
TI  - Conversion of methane to methanol with a bent mono(MU-oxo)dinickel anchored on
      the internal surfaces of micropores.
AB  - The oxidation of methane to methanol is a pathway to utilizing this relatively
      abundant, inexpensive energy resource. Here we report a new catalyst, bent
      mono(MU-oxo)dinickel anchored on an internal surface of micropores,which is
      active for direct oxidation. It is synthesized from the direct loading of a
      nickel precursor to the internal surface of micropores of ZSM5 following
      activation in O2. Ni 2p3/2 of this bent mono(MU-oxo)dinickel species formed on
      the internal surface of ZSM5 exhibits a unique photoemission feature, which
      distinguishes the mono(MU-oxo)dinickel from NiO nanoparticles. The formation of
      the mono(MU-oxo)dinickel species was confirmed with X-ray absorption near-edge
      structure (XANES) and extended X-ray absorption fine structure (EXAFS). This
      mono(MU-oxo)dinickel species is active for the direct oxidation of methane to
      methanol under the mild condition of a temperature as low as 150  degrees C in
      CH4 at 1 bar. In-situ studies using UV-vis, XANES, and EXAFS suggest that this
      bent mono(MU-oxo)dinickel species is the active site for the direct oxidation of
      methane to methanol. The energy barrier of this direct oxidation of methane is
      83.2 kJ/mol. 

PMID- 24896722
TI  - Individual differences in novelty-induced activity and the rewarding effects of
      novelty and amphetamine in rats.
AB  - Previous work has shown that individual differences in locomotor behavior in an
      inescapable novel environment predict the locomotor-stimulant effect of
      amphetamine. Experiment 1 of the present study assessed if novelty-seeking
      behavior in a free choice situation also predicts the locomotor-stimulant effect
      of amphetamine. Rats were first assessed for their locomotor response to an
      inescapable novel environment and then were allowed to choose between this
      environment (familiar) and a novel environment. Activity in the inescapable novel
      environment was found to predict subsequent locomotor response to amphetamine,
      but approach to novelty in the free choice situation did not. In experiment 2,
      rats were assessed for their approach to novelty in the free choice situation and
      then assessed for amphetamine-induced conditioned place preference. It was found
      that rats who spent more time in a novel environment also showed a higher
      magnitude of amphetamine-induced conditioned place preference. These findings are
      consistent with the hypothesis that the rewarding properties of novelty and
      amphetamine may be mediated by a similar brain mechanism. 

PMID- 24896723
TI  - Behavioral contrast using different reinforcers: effect of baseline rate of
      reinforcement.
AB  - The present study determined whether behavioral contrast would occur when
      different reinforcers were delivered in the different components and whether its
      size would vary at different baseline rates of reinforcement. Pigeons pecked keys
      on a multiple variable-interval schedule. Mixed grain was the reinforcer in one
      component and wheat was the reinforcer in the other component. In contrast
      conditions, the rate of wheat reinforcement was increased or decreased, from the
      baseline delivery rate, by a factor of four. Contrast was studied at four
      different baseline rates of reinforcement. Contrast was usually observed and its
      size almost always varied directly with the programmed baseline rate of
      reinforcement. The present results indicate that changes in the condition of
      reinforcement of a different reinforcer can produce contrast. They also broaden
      the potential implications of behavioral contrast. 

PMID- 24896724
TI  - Linear responses.
AB  - Four experiments established complex choice responses a few seconds in duration.
      A response was reinforced if it sufficiently approximated a 'target' response.
      The two target responses in each experiment were linear in the sense that they
      involved either constant rates, or constant rates of change, in component key
      pecking by pigeons. For example, in Experiment 4, one target response consisted
      of the linearly increasing pattern of 0, 1, 2, and 3 pecks per s in four
      successive seconds, and the other response consisted of 3, 2, 1, and 0 pecks per
      s. Contingencies were 'tolerant' in the sense that they permitted variability
      across different reinforced exemplars of a response. Responses approximated
      target responses, at least crudely in terms of overall cumulative records, and
      sometimes even quantitatively in terms of within-trial, local sequential
      organization. In this sense, the 'contents' of at least some choice responses,
      like their 'envelopes', can be shaped. That is, patterning within their
      boundaries, in addition to their relative and absolute durations, can be shaped.
      Some responses may have emerged from variability inherent in component pecking
      occurring at a constant probability, thereby demonstrating a few cases where the
      relation between molecular and molar analyses fully legitimizes a molar analysis.

PMID- 24896725
TI  - Parturition and mother-infant relations in the Indian false vampire bat Megaderma
      lyra.
AB  - The onset and duration of parturition were studied in Megaderma lyra for two
      successive periods during the years 1989 and 1990. The period of parturition fell
      between January and May in 1989, and between March and May in 1990. This change
      in the length of parturition period was not due to variations in the pattern of
      rainfall when prey items are abundant. The young M. lyra clung continuously for 5
      7 days from birth to their mothers whose foraging modality seemed unaffected.
      Grown-up infants were left at a temple roost while the mother bats foraged. On a
      few occasions, mothers and infants were also seen at different 'night roosts'
      found close to the temple roost. In all stages of nursing, the lactating mothers
      had two distinct bouts of foraging, one immediately following emergence (at dusk)
      and the other during their return (at predawn hours) to their main roost. The
      mean lactation period in M. lyra was approximately 70 days. 

PMID- 24896726
TI  - Vibrational communication in Nezara viridula: response of Slovenian and
      Australian bugs to one another.
AB  - Temporal patterns of intersexual vibrational communication between Slovenian and
      Australian populations of Nezara viridula were investigated. The vibrational and
      mating responses of individuals of each sex to individuals of the opposite sex
      from the alternative population were recorded during mating experiments.
      Australian females did not respond to Slovenian males and only a few copulations
      occurred in this direction, whereas Slovenian females and Australian males
      responded to each other and copulated regularly. The two populations probably
      represent distinct sibling species, but this needs to be clarified further.
      Whether the observed mating asymmetry actually occurs regularly in nature, also
      warrants investigation. We suggest how these issues may be resolved. 

PMID- 24896727
TI  - Relative role of olfactory cues and certain non-olfactory factors in foraging of
      fruit-eating bats.
AB  - The proportion of captivated Indian short-nosed fruit bats, Cynopterus sphinx,
      approaching fruits within a specified duration and the fruit-approaching latency
      were recorded under various test conditions (involving variations in the
      olfactory and certain aspects of the physical environment, and the time of food
      presentation). While alterations in the majority of physical features in the
      immediate environment of bats failed to affect either of the foraging parameters
      studied, one or both of them were markedly influenced by the presence of light or
      source of a novel odour, or a delay of 24 h in the regular feeding time. When
      paper pieces coated with homogenized fruit pulp were provided instead of the
      fruit pieces during the regular feeding time, bats responded normally; they,
      however, did not approach water-wetted papers. Initially the bats did not consume
      grapes. However, following the supply of grapes coated with homogenate of banana
      fruits, grapes were approached and consumed in considerable quantities. The
      results underscore that light has a crucial role in the foraging activity of C.
      sphinx and they rely extensively on olfactory cues to detect the fruits. In
      another experiment the bats were daily provided simultaneous access to two
      adjacent fruit-containing cages; fruits in one of the cages were accessible but
      those in the other cage were not. Cedar wood oil, source of a strong odour, was
      placed in either of the cages. Observations revealed that the bats can learn to
      associate the availability of fruits with the presence of an odour within 3 days.

PMID- 24896728
TI  - Flight responses of park fallow deer to the human observer.
AB  - The flight response of fallow deer (Dama dama) towards human observers was
      studied in an enclosed population using fixed transects. Groups took flight less
      often when in open habitats, in large group sizes and at high distances from the
      transect. Flight was also less common where human activity was higher. This
      effect was marked, probably because the study was carried out in an enclosure
      where disturbance was frequent, regular and predictable. We suggest that these
      results may indicate that the flight response of fallow deer depends on the level
      of security provided by their immediate environment and their habituation to
      human presence. In addition, we observed that female groups took flight more
      often than other group types, possibly due to differences in ecological strategy
      whereby protection of young is a high priority for females. One of the most
      striking features of our results was the high inter-individual variability in
      flight response. This emphasises the need for individual-based behavioural
      studies. 

PMID- 24896729
TI  - The effect of frustrative nonreward on vocalisations and behaviour in the laying
      hen, Gallus gallus domesticus.
AB  - Laying hens are thought to express an expectation of a rewarding event through a
      specific vocalisation, the gakel-call. It has been suggested that the gakel-call
      is related to frustration, i.e. the thwarting of behaviour. We investigated if
      frustrative nonreward (nonreinforcement in a situation that previously was
      consistently reinforcing) in laying hens is expressed through this gakel-call.
      Twenty hens of two commercial strains, ten ISA White Leghorn and ten ISA Brown
      Warren were subjected to a classical conditioning procedure. After 23 h of food
      deprivation they were trained, in automated Skinnerboxes, to use red lights as a
      signal (unconditioned stimulus) for a food reward. After this the hens of each
      strain were equally divided into two groups of five. They were subjected to a
      control session (light as conditioned stimulus followed by food reward) and to a
      frustration session (conditioned stimulus followed by nonreward). Both during the
      frustration and control session behaviour and vocalisations were recorded. In the
      White Leghorn strain high levels of alarm-calls are found as indicators of
      anxiety. In the Brown Warren strain more gakel-calls and an increased locomotor
      activity are found after frustrative nonreward. In conclusion, both findings
      suggest that vocalisations could serve as indicators of a laying hen's welfare. 

PMID- 24896730
TI  - Time differences in the emergence of short- and long-term memory during post
      embryonic development in the cuttlefish, Sepia.
AB  - When shown prawns in a glass tube, cuttlefish quickly learn to inhibit their
      predatory behaviour. The available literature suggests that cuttlefish show an
      excellent retention between 2 and 8 min, a recovery of the predatory responses
      around 20 min, and good retention after 1 h of the training phase. These results
      have been interpreted as the product of separate short- and long-term memory
      stores. The retention performance for cuttlefish that learned not to attack prey
      was studied during their post-embryonic development at intervals corresponding to
      the rate of short- (5 min) and long-term (60 min) memory storage definite in
      adult cuttlefish. Short-term memory appeared fully operational as early as 8 days
      of age, whereas the 60-min retention performance increased progressively between
      15 and 60 days of age. Results suggest that during post-embryonic development,
      there is a time lag between the establishment of short- and long-term memory
      systems. 

PMID- 24896731
TI  - Anisotropically functionalized carbon nanotube array based hygroscopic scaffolds.
AB  - Creating ordered microstructures with hydrophobic and hydrophilic moieties that
      enable the collection and storage of small water droplets from the atmosphere,
      mimicking structures that exist in insects, such as the Stenocara beetle, which
      live in environments with limited amounts of water. Inspired by this approach,
      vertically aligned multiwalled carbon nanotube forests (NTFs) are asymmetrically
      end-functionalized to create hygroscopic scaffolds for water harvesting and
      storage from atmospheric air. One side of the NTF is made hydrophilic, which
      captures water from the atmosphere, and the other side is made superhydrophobic,
      which prevents water from escaping and the forest from collapsing. To understand
      how water penetrates into the NTF, the fundamentals of water/NTF surface
      interaction are discussed. 

PMID- 24896733
TI  - Shaped Pd-Ni-Pt core-sandwich-shell nanoparticles: influence of Ni sandwich
      layers on catalytic electrooxidations.
AB  - Shape-controlled metal nanoparticles (NPs) interfacing Pt and nonprecious metals
      (M) are highly active energy conversion electrocatalysts; however, there are
      still few routes to shaped M-Pt core-shell NPs and fewer studies on the geometric
      effects of shape and strain on catalysis by such structures. Here, well-defined
      cubic multilayered Pd-Ni-Pt sandwich NPs are synthesized as a model platform to
      study the effects of the nonprecious metal below the shaped Pt surface. The
      combination of shaped Pd substrates and mild reduction conditions directs the Ni
      and Pt overgrowth in an oriented, layer-by-layer fashion. Exposing a majority of
      Pt(100) facets, the catalytic performance in formic acid and methanol electro
      oxidations (FOR and MOR) is assessed for two different Ni layer thicknesses and
      two different particle sizes of the ternary sandwich NPs. The strain imparted to
      the Pt shell layer by the introduction of the Ni sandwich layer (Ni-Pt lattice
      mismatch of ~11%) results in higher specific initial activities compared to core
      shell Pd-Pt bimetallic NPs in alkaline MOR. The trends in activity are the same
      for FOR and MOR electrocatalysis in acidic electrolyte. However, restructuring in
      acidic conditions suggests a more complex catalytic behavior from changes in
      composition. Notably, we also show that cubic quaternary Au-Pd-Ni-Pt multishelled
      NPs, and Pd-Ni-Pt nanooctahedra can be generated by the method, the latter of
      which hold promise as potentially highly active oxygen reduction catalysts. 

PMID- 24896732
TI  - Click modification of RNA at adenosine: structure and reactivity of 7-ethynyl-
      and 7-triazolyl-8-aza-7-deazaadenosine in RNA.
AB  - Ribonucleoside analogues bearing terminal alkynes, including 7-ethynyl-8-aza-7
      deazaadenosine (7-EAA), are useful for RNA modification applications. However,
      although alkyne- and triazole-bearing ribonucleosides are in widespread use, very
      little information is available on the impact of these modifications on RNA
      structure. By solving crystal structures for RNA duplexes containing these
      analogues, we show that, like adenosine, 7-EAA and a triazole derived from 7-EAA
      base pair with uridine and are well-accommodated within an A-form helix. We show
      that copper-catalyzed azide/alkyne cycloaddition (CuAAC) reactions with 7-EAA are
      sensitive to the RNA secondary structure context, with single-stranded sites
      reacting faster than duplex sites. 7-EAA and its triazole products are recognized
      in RNA template strands as adenosine by avian myoblastosis virus reverse
      transcriptase. In addition, 7-EAA in RNA is a substrate for an active site mutant
      of the RNA editing adenosine deaminase, ADAR2. These studies extend our
      understanding of the impact of these novel nucleobase analogues and set the stage
      for their use in probing RNA structure and metabolism. 

PMID- 24896734
TI  - Ultrasonographic findings in the ovine udder during involution.
AB  - The objective of the study was to record, by means of ultrasonographic
      examination, changes occurring in the udder of ewes during involution and to
      compare differences between progressive or abrupt udder drying-off. In group A
      ewes, udder drying-off took place progressively during a period of 22 d; ewes
      were milked twice daily for the last time on day(D) 0; then, they were hand
      milked once daily for a week (D1-D7), which was followed by another week during
      which ewes were hand-milked once every 2 d (D9, D11, D13), followed by a third
      week during which ewes were hand-milked once every 3 d (D16, D19, D22). In group
      B ewes, the procedure took place abruptly; ewes were milked twice daily for the
      last time on D0 and no milking was carried out after that. B-mode and Doppler
      ultrasonographic examination of the udder of all ewes was performed throughout
      the drying-off procedure. Appropriate data management and analysis were
      performed. Progressive changes of the various parameters evaluated throughout the
      study period were significant in both groups (P<0.005). Gray-scale results of
      mammary parenchyma progressively decreased during the study and differed
      significantly between group A and group B (P=0.049). A temporary increase in
      cistern volume was evident after cessation of lactation, but differences were not
      significant between the two groups (P>0.3). Diameter of the external pudendal
      artery progressively decreased during the study and differed significantly
      between the two groups (P=0.037). Both resistance index and pulsatility index
      progressively increased throughout the study period in both groups; for both
      parameters, differences between the two groups were significant (P<0.0005). B
      mode ultrasonographic examination indicated differences in remodelling of the
      extracellular matrix in relation to the procedure for udder drying-off. Volume of
      the gland cistern did not appear to be affected by the procedure for udder drying
      off. Doppler ultrasonographic examination confirmed that blood flow during
      initiated involution was lower than during a progressive procedure for drying
      off.

PMID- 24896735
TI  - High transfection efficiency of quantum dot-antisense oligonucleotide
      nanoparticles in cancer cells through dual-receptor synergistic targeting.
AB  - Incorporating ligands with nanoparticle-based carriers for specific delivery of
      therapeutic nucleic acids (such as antisense oligonucleotides and siRNA) to tumor
      sites is a promising approach in anti-cancer strategies. However, nanoparticle
      based carriers remain insufficient in terms of the selectivity and transfection
      efficiency. In this paper, we designed a dual receptor-targeted QDs gene carrier
      QD-(AS-ODN+GE11+c(RGDfK)) which could increase the cellular uptake efficiency and
      further enhance the transfection efficiency. Here, the targeting ligands used
      were peptides GE11 and c(RGDfK) which could recognize epidermal growth factor
      receptors (EGFR) and integrin alphanubeta3 receptors, respectively. Quantitative
      flow cytometry and ICP/MS showed that the synergistic effect between EGFR and
      integrin alphanubeta3 increased the cellular uptake of QDs carriers. The effects
      of inhibition agents showed the endocytosis pathway of QD-(AS-ODN+GE11+c(RGDfK))
      probe was mainly clathrin-mediated. Western blot confirmed that QD-(AS
      ODN+GE11+c(RGDfK)) could further enhance gene silencing efficiency compared to QD
      (AS-ODN+GE11) and QD-(AS-ODN+c(RGDfK)), suggesting this dual receptor-targeted
      gene carrier achieved desired transfection efficiency. In this gene delivery
      system, QDs could not only be used as a gene vehicle but also as fluorescence
      probe, allowing for localization and tracking during the delivery process. This
      transport model is very well referenced for non-viral gene carriers to enhance
      the targeting ability and transfection efficiency. 

PMID- 24896736
TI  - Autoantibodies to C-reactive protein in incomplete lupus and systemic lupus
      erythematosus.
AB  - OBJECTIVE: Anti-C-reactive protein (CRP) antibodies have been described in
      patients with systemic lupus erythematosus (SLE). We investigated the potential
      of the anti-CRP antibody as a marker for disease activity in SLE patients and as
      a predictor of progression to SLE in patients with incomplete lupus. METHODS:
      Immunoglobulin G anti-CRP antibody levels were measured using an enzyme-linked
      immunosorbent assay. RESULTS: Patients with incomplete lupus exhibited clinical
      and immunologic characteristics different from those in SLE patients: no
      serositis and alopecia, more common oral ulcers and arthritis, lower disease
      activity index, lower positivity for antinuclear and anti-double-strand DNA
      antibodies, and higher complement levels. Anti-CRP antibody levels were higher in
      SLE patients (35.6 [35.1] AU) than in patients with incomplete lupus (23.1 [25.8]
      AU, P = 0.016) and normal controls (21.0 [14.3] AU, P < 0.001). Anti-CRP antibody
      was significantly higher in SLE patients with arthritis and correlated with
      disease activity markers, including antichromatin antibody. However, no
      difference in anti-CRP antibody levels was observed between patients with
      incomplete lupus that progressed to SLE and those whose did not. CONCLUSION:
      These data suggest that anti-CRP antibodies can neither be used as biomarkers in
      SLE nor predict SLE progression in patients with incomplete lupus.

PMID- 24896738
TI  - Spine.

PMID- 24896739
TI  - Measurements and classifications in spine imaging.
AB  - Imaging criteria and radiologic measurements play a key role in the diagnosis of
      spinal diseases. In addition, they often create the basis of classification
      systems that determine the severity of the disease and thereby enable a stage
      related therapy. A clearly defined nomenclature for imaging findings as well as
      standardized and thoroughly evaluated methods of measurement are necessary to
      achieve a sufficiently high diagnostic accuracy. Various specialized committees
      dealing with the diagnosis of spinal diseases have made efforts within the last
      years to develop diagnostic standards. This review provides an overview of
      radiologic measurements and classification systems that are currently used for
      the diagnosis of scoliosis and degenerative diseases of the lumbar spine.

PMID- 24896740
TI  - Basic aspects in MR imaging of degenerative lumbar disk disease.
AB  - Degenerative disease may lead to spinal canal stenosis and long-lasting pain. It
      is among the leading cause of disability that may affect the ability to work. It
      has become more common in an increasingly aging population. MRI is the most
      comprehensive imaging modality and provides detailed morphologic information. A
      standardized terminology facilitates communication with referring physicians. Yet
      imaging findings need careful interpretation in conjunction with the results of
      clinical tests and symptoms to truly help guide therapeutic decision making. This
      review summarizes aspects of normal anatomy of the intervertebral disk,
      pathologic mechanisms, terminology, and examples of the imaging spectrum of disk
      degeneration and herniation.

PMID- 24896741
TI  - The traumatized vertebral spine reloaded: injury mechanisms and their radiologic
      patterns.
AB  - The ideal classification of spinal trauma does not yet exist, primarily because
      the implementation of morphological, biomechanical, and clinical parameters in a
      single nomenclature is a difficult task. For radiologists and surgeons, who are
      partners in trauma teams, only a few classifications of injury patterns have been
      shown to be useful enough to provide rapid and stable therapy decisions in daily
      practice. From a didactic point of view, however, simplifications of injury
      mechanisms are of help to become aware of the most important radiologic injury
      patterns of vertebral trauma. The members of trauma teams should be aware of the
      strengths and limitations of existing descriptions of imaging features when
      reporting trauma to the spine. These are discussed in this article.

PMID- 24896737
TI  - Indoor exposure and adverse birth outcomes related to fetal growth, miscarriage
      and prematurity-a systematic review.
AB  - The purpose of this review was to summarize existing epidemiological evidence of
      the association between quantitative estimates of indoor air pollution and all
      day personal exposure with adverse birth outcomes including fetal growth,
      prematurity and miscarriage. We carried out a systematic literature search of
      MEDLINE and EMBASE databases with the aim of summarizing and evaluating the
      results of peer-reviewed epidemiological studies undertaken in "westernized"
      countries that have assessed indoor air pollution and all-day personal exposure
      with specific quantitative methods. This comprehensive literature search
      identified 16 independent studies which were deemed relevant for further review
      and two additional studies were added through searching the reference lists of
      all included studies. Two reviewers independently and critically appraised all
      eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of
      the 18 selected studies, 14 adopted a prospective cohort design, three were case
      controls and one was a retrospective cohort study. In terms of pollutants of
      interest, seven studies assessed exposure to electro-magnetic fields, four
      studies assessed exposure to polycyclic aromatic hydrocarbons, four studies
      assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise
      exposure respectively. Furthermore, 12 studies examined infant growth as the main
      birth outcome of interest, six examined spontaneous abortion and three studies
      assessed gestational age at birth and preterm delivery. This survey demonstrates
      that there is insufficient research on the possible association of indoor
      exposure and early life effects and that further research is needed. 

PMID- 24896742
TI  - Spine and sport.
AB  - The spine, in athletes is a relatively frequent origin of problems. Chronic spine
      problems are much more common compared to acute injuries. Chronic injuries to the
      spine most often occur in low-contact sports like gymnastics and are most
      commonly the result of overuse. Acute injuries are more common in high-speed and
      full contact sports and are traumatic in origin. Injuries to the spinal cord can
      be devastating but are fortunately very uncommon. Although imaging of the spine
      appears to be straightforward, any radiologist will acknowledge that the optimal
      imaging strategy is often unclear due to several reasons. For the cervical spine
      much has improved since the NEXUS and CCR studies appeared in which clear rules
      were defined when to image the C-spine in acute trauma situations. For the
      thoracic and lumbar spines such rules are not defined. Although conventional
      imaging has long been the primary imaging modality of choice there is ample
      evidence that this should be abandoned in favor of multidetector CT for the C
      spine. This is reflected in the ACR criteria in which conventional imaging of
      tile C-spine in trauma is rated as the least appropriate imaging method. However,
      this is not true in children and adolescents although a strict age criterion is
      not defined. It is also not true for injuries to the thoracic and lumbar spine in
      which conventional imaging still plays a large role as primary imaging modality
      followed by evaluation by CT in trauma situations. The role for MRI in acute
      situations is increasing especially with the increasing use of the TLICS system
      to classify injuries of the thoracic and lumbar spine in which the evaluation of
      the integrity of the posterior ligamentous structures is included. For the
      evaluation of chronic complaints, the roles of CT and MRI are basically reversed
      in which MRI will become the prime imaging modality of choice after conventional
      imaging after which CT can be reserved for a selected patient group. The merit of
      the different imaging modalities will be discussed together with a spectrum of
      acute and chronic injuries often encountered in the spine in athletes.

PMID- 24896744
TI  - Primary tumors of the spine.
AB  - Spinal tumors consist of a large spectrum of various histologic entities.
      Multiple spinal lesions frequently represent known metastatic disease or
      lymphoproliferative disease. In solitary lesions primary neoplasms of the spine
      should be considered. Primary spinal tumors may arise from the spinal cord, the
      surrounding leptomeninges, or the extradural soft tissues and bony structures. A
      wide variety of benign neoplasms can involve the spine including enostosis,
      osteoid osteoma, osteoblastoma, aneurysmal bone cyst, giant cell tumor, and
      osteochondroma. Common malignant primary neoplasms are chordoma, chondrosarcoma,
      Ewing sarcoma or primitive neuroectodermal tumor, and osteosarcoma. Although
      plain radiographs may be useful to characterize some spinal lesions, magnetic
      resonance imaging is indispensable to determine the extension and the
      relationship with the spinal canal and nerve roots, and thus determine the plan
      of management. In this article we review the characteristic imaging features of
      extradural spinal lesions.

PMID- 24896743
TI  - Imaging and interpretation of axial spondylarthritis: the radiologist's
      perspective--consensus of the Arthritis Subcommittee of the ESSR.
AB  - This article reflects the radiologist's perspective on the imaging and
      interpretation of axial spondylarthritis (SpA). The arthritis subcommittee of the
      European Society of Skeletal Radiology provides a consensus for the following
      questions: When and how should we image? How should we analyze the images? How
      should we interpret the imaging findings? To answer these questions, we address
      the indications in imaging axial SpA and the different imaging techniques, with a
      special focus on magnetic resonance imaging protocols. The value of different
      imaging modalities is discussed. For adequate image analysis, knowledge of the
      anatomy and the pathologic changes in chronic and acute inflammation of the
      sacroiliac joints and the spine is mandatory. Differential diagnoses of
      inflammatory lesions of the sacroiliac joints and the spine are addressed due to
      their importance in image interpretation.

PMID- 24896745
TI  - The postoperative spine.
AB  - Potential complications following spinal surgery include neural compression due
      to hematoma, recurrent disk herniation, epidural fibrosis, dural tear with
      pseudomeningocele formation, and infection. Specific complications relate to the
      use of spinal instrumentation that include incorrectly positioned instrumentation
      and failure of spinal fusion leading to instrumentation loosening or breakage. To
      interpret the postoperative imaging correctly, it is necessary to understand the
      nature of the surgical procedure that has been performed and the normal
      postoperative appearances. Magnetic resonance imaging is the mainstay in the
      evaluation of the postoperative spine. Radiographs and computed tomography
      continue to have a major role in assessing fusion and in the assessment of
      complications related to instrumentation.

PMID- 24896746
TI  - Interventional procedures of the spine.
AB  - Different interventional procedures performed under imaging guidance permit the
      diagnosis and treatment of the many causes of back pain. Sources of pain amenable
      to be treated include facet joints, vertebral body, intervertebral disk, and
      paraspinal structures including nerves and ganglion roots. These procedures may
      be merely diagnostic, therapeutic, or intended for both purposes. We review the
      main indications, advantages, and complications of these techniques.

PMID- 24896747
TI  - Traumatic myelopathy: current concepts in imaging.
AB  - Traumatic myelopathy is a frequent complication after spinal trauma. The
      prognosis is often very poor, and the condition has important socioeconomic
      consequences. Knowledge of the epidemiology and imaging features is mandatory to
      ensure correct diagnosis and timely intervention. Imaging studies play an
      increasing role in the diagnosis and follow-up of this condition. Computed
      tomography remains the first-line investigation whenever spinal cord injury is
      suspected. It may indicate the presence of spinal cord lesions by visualizing
      vertebral lesions, but it cannot assess the spinal cord itself. Magnetic
      resonance imaging (MRI) can depict possible spinal cord edema, hemorrhage, or
      transection, and it is essential in diagnosing and predicting the outcome of
      spinal cord injury. Follow-up should also be performed with MRI to evaluate long
      term intramedullary changes. Diffusion-weighted imaging and diffusion tensor
      imaging are promising new techniques that allow very early detection of spinal
      cord injury by measuring the diffusion within the spinal cord, thereby providing
      information on white matter integrity. However, technical limitations of these
      new techniques prompt further investigation to improve specificity.

PMID- 24896748
TI  - Anatomy and histology of the sacroiliac joints.
AB  - The anatomy of joints provides an important basis for understanding the nature
      and imaging of pathologic lesions and their imaging appearance. This applies
      especially to the sacroiliac (SI) joints, which play a major role in the
      diagnosis of spondyloarthritis. They are composed of two different joint
      portions, a cartilage-covered portion ventrally and a ligamentous portion
      dorsally, and thus rather complex anatomically. Knowledge of anatomy and the
      corresponding normal imaging findings are important in the imaging diagnosis of
      sacroiliitis, especially by MR imaging. A certain distinction between the two
      joint portions by MR imaging is only obtainable by axial slice orientation.
      Together with a perpendicular coronal slice orientation, it provides adequate
      anatomical information and thereby a possibility for detecting the anatomical
      site of disease-specific characteristics and normal variants simulating disease.
      This overview describes current knowledge about the normal macroscopic and
      microscopic anatomy of the SI joints.

PMID- 24896749
TI  - Shape-selective dependence of room temperature ferromagnetism induced by
      hierarchical ZnO nanostructures.
AB  - We report on the room temperature ferromagnetism of various highly crystalline
      zinc oxide (ZnO) nanostructures, such as hexagonally shaped nanorods, nanocups,
      nanosamoosas, nanoplatelets, and hierarchical nano "flower-like" structures.
      These materials were synthesized in a shape-selective manner using simple
      microwave assisted hydrothermal synthesis. Thermogravimetric analyses
      demonstrated the as-synthesized ZnO nanostructures to be stable and of high
      purity. Structural analyses showed that the ZnO nanostructures are
      polycrystalline and wurtzite in structure, without any secondary phases.
      Combination of electron paramagnetic resonance, photoluminescence, and X-ray
      photoelectron spectroscopy studies revealed that the zinc vacancies (VZn) and
      singly ionized oxygen vacancies (VO(+)) located mainly on the ZnO surface are the
      primary defects in ZnO structures. A direct link between ferromagnetism and the
      relative occupancy of the VZn and VO(+) was established, suggesting that both VZn
      and VO(+) on the ZnO surface plays a vital role in modulating ferromagnetic
      behavior. An intense structure- and shape-dependent ferromagnetic signal with an
      effective g-value of >2.0 and a sextet hyperfine structure was shown. Moreover, a
      novel low field microwave absorption signal was observed and found to increase
      with an increase in microwave power and temperature. 

PMID- 24896751
TI  - Consumer use of over-the-counter proton pump inhibitors in patients with
      gastroesophageal reflux disease.
AB  - OBJECTIVES: Optimal administration of proton pump inhibitor (PPI) for the
      treatment of gastroesophageal reflux disease (GERD) requires consideration of
      meal timing. Since becoming available over the counter (OTC), no studies have
      assessed treatment patterns and symptom control in OTC consumers. The objective
      of this study was to survey dosing patterns and symptom control in OTC and
      prescription PPI users. METHODS: Patients at five clinics were surveyed regarding
      diagnosis of GERD, use of OTC or prescription PPIs, information on time of day
      dosing, demographics, and Gastroesophageal Reflux Disease Symptom Assessment
      Scale (GSAS; 2001, Johnson & Johnson). RESULTS: Of the 1,959 patients surveyed,
      610 (31%) used PPIs for GERD. Of these, 190 (31%) and 223 (37%) received
      prescriptions from gastroenterologists (GIs) and primary care physicians (PCPs),
      respectively; 197 (32%) purchased OTC PPIs. Of the patients prescribed PPIs by
      GIs, 71% were optimal users, whereas 47% of patients receiving prescriptions from
      PCPs and 39% of consumers used PPIs optimally (P<0.001 compared with GIs). GSAS
      symptom, frequency, and severity scores were significantly better in patients
      prescribed PPIs by GIs (all P<0.001, GI compared with PCP and consumer). GSAS
      symptom, frequency, and severity scores were also significantly better in
      patients using PPIs optimally (P<0.001 for all parameters) compared with those
      taking PPIs suboptimally or excessively. CONCLUSIONS: Patients receiving
      prescription PPI from a GI are more likely to be optimal users with better
      symptom control. Conversely, consumers are more likely to be suboptimal users
      with inadequate symptom control.

PMID- 24896752
TI  - Images of the month: Esophageal dysphagia secondary to erosion of cervical spine
      hardware.

PMID- 24896753
TI  - Continuing medical education: June 2014.

PMID- 24896755
TI  - Continuing medical education: June 2014.

PMID- 24896757
TI  - Shining a new narrow band of light on old problems.
AB  - Improvements in narrow band imaging (NBI) may provide an improved view of colonic
      mucosa for detection of polyps and adenomas. In this issue, Leung et al. report
      findings to suggest that this next-generation NBI technology is superior to
      conventional high-definition white light endoscopy in polyp detection. These
      findings are based on brighter illumination, which has been a problem with older
      generations of NBI, which did not increase polyp detection but were useful for
      polyp characterization. Although these findings are very promising for this new
      role of second-generation NBI in polyp detection, the study must be viewed with
      consideration of the history of the older NBI system, the analysis of which
      through multiple positive and negative studies ultimately led to the conclusion
      that it was not beneficial for detection. 

PMID- 24896758
TI  - IBS with constipation, functional constipation, painful and non-painful
      constipation: e Pluribus...Plures?
AB  - IBS with constipation (IBS-C) and chronic constipation (CC) can be difficult to
      distinguish clinically. The Rome III criteria create mutual exclusion between IBS
      C and CC, based on the presence of abdominal pain, which is a defining criterion
      for IBS-C. Previous surveys found that up to 45% of CC patients have abdominal
      pain and other IBS features. A Spanish general population study proposes a
      subclassification of patients with CC based on abdominal pain and other features
      of IBS. As the Rome criteria evolve, these and other observations provide the
      basis for further efforts in discerning key features of IBS-C and CC. 

PMID- 24896759
TI  - Pharmacologic prophylaxis alone is not adequate to prevent post-ERCP
      pancreatitis.
AB  - Post-ERCP pancreatitis (PEP) remains the most common complication following ERCP.
      Although once considered unpredictable, understanding patient and procedure
      related risk factors, and measures such as pancreatic stent placement and
      pharmacoprophylaxis have been shown to substantially decrease the risk of PEP. In
      this issue of the Journal, the role of pharmacoprophylaxis is explored in a study
      comparing rectal indomethacin plus sublingual nitrates vs. rectal indomethacin
      alone. While showing improved efficacy, dual pharmacoprophylaxis does not appear
      adequate to obviate the importance of technique-related variables and pancreatic
      stents. Rather, a comprehensive approach is likely to be the most efficacious
      strategy to reduce PEP. 

PMID- 24896760
TI  - Aggression of C-difficile infections in PPI consumers.

PMID- 24896761
TI  - Response to Daniell.

PMID- 24896762
TI  - Photosensitivity induced by mesalazine: report of a case.

PMID- 24896763
TI  - Outcomes from rectal vancomycin therapy in patients with Clostridium difficile
      infection.

PMID- 24896765
TI  - Gastric lymphocytic phlebitis as a differential diagnosis of linitis plastica.

PMID- 24896764
TI  - PACSIN2 does not influence thiopurine-related toxicity in patients with
      inflammatory bowel disease.

PMID- 24896767
TI  - Metastases to hernial sac detected on (18)F-FDG PET/CT.
AB  - The presence of primary or metastatic cancer within a hernial sac is uncommon.
      Based on the anatomical relation of the tumor to the sac, malignant tumors within
      hernia sac are classified into 3 groups; intrasaccular, saccular, and
      extrasaccular. We present F-FDG PET/CT images of 2 cases of hernia sac
      metastasis, one from non-small cell lung cancer and another from infiltrating
      ductal breast carcinoma. F-FDG PET/CT was useful in these cases for detection of
      the metastatic lesion within hernial sac and thus in assessment of total disease
      burden. 

PMID- 24896768
TI  - Consequences of kriging and land use regression for PM2.5 predictions in
      epidemiologic analyses: insights into spatial variability using high-resolution
      satellite data.
AB  - Many epidemiological studies use predicted air pollution exposures as surrogates
      for true air pollution levels. These predicted exposures contain exposure
      measurement error, yet simulation studies have typically found negligible bias in
      resulting health effect estimates. However, previous studies typically assumed a
      statistical spatial model for air pollution exposure, which may be
      oversimplified. We address this shortcoming by assuming a realistic, complex
      exposure surface derived from fine-scale (1 km * 1 km) remote-sensing satellite
      data. Using simulation, we evaluate the accuracy of epidemiological health effect
      estimates in linear and logistic regression when using spatial air pollution
      predictions from kriging and land use regression models. We examined chronic
      (long-term) and acute (short-term) exposure to air pollution. Results varied
      substantially across different scenarios. Exposure models with low out-of-sample
      R(2) yielded severe biases in the health effect estimates of some models, ranging
      from 60% upward bias to 70% downward bias. One land use regression exposure model
      with >0.9 out-of-sample R(2) yielded upward biases up to 13% for acute health
      effect estimates. Almost all models drastically underestimated the SEs. Land use
      regression models performed better in chronic effect simulations. These results
      can help researchers when interpreting health effect estimates in these types of
      studies.

PMID- 24896769
TI  - Infant toenails as a biomarker of in utero arsenic exposure.
AB  - A growing body of evidence suggests that in utero and early-life exposure to
      arsenic may have detrimental effects on children, even at the low to moderate
      levels common in the United States and elsewhere. In a sample of 170 mother
      infant pairs from New Hampshire, we determined infant exposure to in utero
      arsenic by evaluating infant toenails as a biomarker using inductively coupled
      plasma mass spectrometry. Infant toenail arsenic concentration correlated with
      maternal postpartum toenail concentrations (Spearman's correlation coefficient
      0.34). In adjusted linear models, a doubling of maternal toenail arsenic
      concentration was associated with a 53.8% increase in infant toenail arsenic
      concentration as compared with 20.4% for a doubling of maternal urine arsenic
      concentration. In a structural equation model, a doubling of the latent variable
      integrating maternal toenail and urine arsenic concentrations was associated with
      a 67.5% increase in infant toenail arsenic concentration. A similar correlation
      between infant and maternal postpartum toenail concentrations was observed in a
      validation cohort of 130 mother-infant pairs from Rhode Island. In utero exposure
      to arsenic occurs through maternal water and dietary sources, and infant toenails
      appear to be a reliable biomarker for estimating arsenic exposure during the
      critical window of gestation. 

PMID- 24896771
TI  - Bilateral Orbital Abscesses After Strabismus Surgery.
AB  - Infectious orbital complications after strabismus surgery are rare. Their
      incidence is estimated to be 1 case per 1,100 surgeries and include preseptal
      cellulitis, orbital cellulitis, subconjunctival and sub-Tenon's abscesses,
      myositis, and endophthalmitis. This report describes the case of an otherwise
      healthy 3-year-old boy who underwent bilateral medial rectus recession and
      disinsertion of the inferior obliques. A few days after surgery, the patient
      presented with bilateral periorbital edema and inferotemporal chemosis. A series
      of CT scans with contrast revealed inferotemporal orbital collections OU. The
      patient immediately underwent transconjunctival drainage of fibrinous and
      seropurulent collections in the sub-Tenon's space and experienced rapid
      improvement a few days later. The patient is reported to be in stable condition
      in a follow-up examination performed more than a year after the reported events. 

PMID- 24896772
TI  - Thyroid Eye Disease With Significant Levator Involvement and Ptosis: A Case
      Report.
AB  - A case of an 87-year-old woman with a history of Graves disease presenting with a
      5-year history of severe ptosis and very poor levator function of the left side
      is presented. MRI revealed marked enlargement of all extraocular muscles and
      significant enlargement of the left levator muscle. Given the patient's age and
      atypical presentation of thyroid eye disease (TED), she was taken to the
      operating room for biopsy and ptosis repair with frontalis suspension.
      Histopathological analysis revealed chronic inflammation and fibrosis consistent
      with Graves disease. 

PMID- 24896770
TI  - Sirt1 deletion leads to enhanced inflammation and aggravates endotoxin-induced
      acute kidney injury.
AB  - Bacterial endotoxin has been known to induce excessive inflammatory responses and
      acute kidney injury. In the present study, we used a mouse model of endotoxemia
      to investigate the role of Sirt1 in inflammatory kidney injury. We examined
      molecular and cellular responses in inducible Sirt1 knockout (Sirt1-/-) mice and
      wild type littermates (Sirt1+/+) in lipopolysaccharide (LPS)-induced kidney
      injury. Our studies demonstrated that Sirt1 deletion caused aggravated kidney
      injury, which was associated with increased inflammatory responses including
      elevated pro-inflammatory cytokine production, and increased ICAM-1 and VCAM-1
      expression. Inflammatory signaling such as STAT3/ERK phosphorylation and NF
      kappaB activation was markedly elevated in kidney tissues of Sirt1 knockout mice
      after LPS challenge. The results indicate that Sirt1 is protective against LPS
      induced acute kidney injury by suppressing kidney inflammation and down
      regulating inflammatory signaling. 

PMID- 24896773
TI  - Negative pressure wound therapy in preseptal orbital cellulitis complicated with
      necrotizing fasciitis and preseptal abscess.
AB  - PURPOSE: Preseptal cellulitis (PC) may be locally complicated with abscess
      formation and necrotizing fasciitis. If not treated promptly and adequately, it
      may result in further complications. The authors report a series of patients
      where negative pressure wound therapy (NPWT) proved a safe and valuable adjunct
      therapy in avoiding complications of PC and in accelerating wound healing.
      METHODS: A 4 patient case series. Four male patients (11 months to 58 years old)
      with unilateral complicated PC. INTERVENTIONS: Patients were admitted with PC and
      treated initially with specific intravenous antibiotic therapy. These patients
      did not respond adequately; therefore, surgical drainage and/or debridement were
      performed. After surgery, persistent edema and purulent discharge was observed
      prompting the need for adjunct NPWT every 48 to 72 hours. NPWT is the use of
      vacuum through a wound filler material covered with an airtight drape connected
      to a pump. Complete ophthalmologic examination was performed after each 48-hour
      cycle. Length of hospital stay, days from surgery to discharge, days from start
      of NPWT to discharge, clinical improvement, and safety. RESULTS: Four patients
      were diagnosed with PC between 2 and 5 days of evolution. Two diabetic adults
      developed the condition secondary to trauma, the adolescent as a result of a
      cosmetic piercing, and the infant associated to sinusitis. NPWT reached -125
      mm.Hg, except for the infant who received -75 mm.Hg. The average number of days
      necessary for improvement with NPWT was 6.7 days. Only 2 patients required
      surgical reconstruction. Time from debridement to discharge was in average 13.5
      days. No ocular complications were observed, and follow up was satisfactory with
      normal eyelid function and aesthetics and preserved visual acuity. CONCLUSIONS:
      NPWT proved to be safe and effective for treating locally complicated PC as an
      adjuvant therapy to antibiotic and surgical treatment that decreased the length
      of hospital stay, and the time for recovery in patients that were slow
      responders. No ocular complications were observed in any of these patients'
      follow up ranging from 1 to 4 years.

PMID- 24896774
TI  - Hydroxyapatite orbital implant in children following enucleation: analysis of 531
      sockets.
AB  - PURPOSE: To evaluate the features and long-term outcomes of hydroxyapatite (HA)
      orbital implant following enucleation in pediatric patients. METHODS: A
      retrospective review was performed on clinical records of patients <=18 years of
      age , managed with enucleation and HA implant placement. Recorded outcomes
      included implant-related complications, implant and prosthesis motility, and
      patient cosmetic satisfaction. RESULTS: There were 525 children (531 sockets)
      with HA implant following enucleation. The mean age at HA implant placement was 3
      years (median, 2 years; range, 4 days to 17 years). Indications for enucleation
      included retinoblastoma (n = 457, 86%), uveal melanoma (n = 17, 3%),
      medulloepithelioma (n = 8, 2%), and others (n = 49, 9%). The HA implant was
      uncoated (n = 370, 70%) or polymer coated (n = 161, 30%). For the 370 uncoated
      implants, wrapping was provided with scleral (n = 346, 94%) or bovine pericardium
      (n = 1, <1%), and 23 patients (6%) had no wrapping. The extraocular muscles were
      attached to the implant/polymer coat/wrap (n = 531, 100%), by suturing 4 rectus
      muscles (n = 349, 66%) or all 6 muscles (n = 182, 34%). Over mean follow up of 60
      months, in 477 orbital implants, complications included conjunctival thinning (n
      = 10, 2%), implant infection (n = 6, 1%), implant exposure (n = 13, 3%), and
      implant migration/extrusion (n = 0, 0%). Motility for implant was judged as
      excellent (n = 245, 78%) and small-angle prosthesis motility was excellent (n =
      196, 59%). Patient/family satisfaction with cosmetic outcome was rated as
      excellent in 471 implants (99%). CONCLUSIONS: Following enucleation in children,
      long-term outcomes of the HA orbital implant are excellent with favorable patient
      cosmetic satisfaction and rare complication.

PMID- 24896775
TI  - The use of Whitnall's ligament for sling redirection in frontalis suspension
      ptosis surgery.
AB  - PURPOSE: To evaluate the cosmetic and functional outcome of a modified frontalis
      suspension technique when the sling force vector is redirected through Whitnall's
      ligament. METHODS: Non-comparative retrospective study. Twenty-nine eyes of 23
      patients with poor levator function of 4 mm or less. Patients underwent frontalis
      suspension with polytetrafluoroethylene (Gore-Tex) (PTFE). The sling was inserted
      in a single circular fashion through 3 brow incisions. An additional eyelid
      crease incision was created to allow the passage of the sling beneath Whitnalls'
      ligament, to permit securing the sling to the tarsus, to perform a limited
      blepharoplasty, and to reform the eyelid crease. Postoperatively, patients were
      followed up for at least 24 months. RESULTS: All cases achieved elevation of the
      ptotic eyelid in the primary position. Three eyes of 2 patients had under
      correction in the primary gaze. Twenty-eight of 29 eyes retained the same level
      of eyelid elevation after 2 years of follow up. Symmetry in the primary gaze was
      achieved in 4 of 6 (67%) patients with bilateral ptosis and in 12 of 17 (71%)
      patients with unilateral ptosis. One patient had sling infection with granuloma
      formation. Lagophthalmos was common, but none developed exposure keratitis.
      CONCLUSIONS: Frontalis suspention technique modified with redirecting the sling
      pulling force vector by passing beneath Whitnall's ligament can achieve a natural
      looking eyelid in primary gaze and does not interfere with functional outcome.

PMID- 24896776
TI  - Electron microscopic features of nasal mucosa treated with topical and
      circumostial injection of mitomycin C: implications in dacryocystorhinostomy.
AB  - PURPOSE: To evaluate the ultrastructural effects of topical and circumostial
      injection of mitomycin C (COS-MMC) on nasal mucosa and compare them with the
      controls. The study also aimed at classifying the subcellular effects in detail.
      METHODS: The nasal mucosa of 6 patients were subjected to 0.02% of mitomycin C
      for 3 minutes (3 patients) and 0.02% COS-MMC (3 patients) as per standard
      protocol, during endoscopic dacryocystorhinostomy. Normal nasal mucosa from
      untreated areas (2 each from topical and COS-MMC groups) were taken as controls
      after harvesting the treated areas. Full thickness tissues (5 mm * 5 mm) were
      collected for transmission electron microscopy, and ultrastructural effects were
      evaluated. RESULTS: Both topical and COS-MMC showed significant and distinct
      ultrastructural changes involving the epithelial, glandular, vascular, and
      fibrocollagenous tissues compared with the controls. There were profound changes
      within fibroblasts with intracellular edema, pleomorphic and vesicular
      mitochondria, dilated smooth and rough endoplasmic reticulum, and chromatin
      condensation. In addition, COS-MMC samples showed subepithelial hypocellularity
      with limited disorganization of structure. The changes in both the MMC groups
      were restricted to treated areas only. CONCLUSIONS: Both topical and COS-MMC show
      profound changes in nasal mucosa with more marked changes in COS-MMC group. These
      changes being limited in nature may help in enhancing the success of
      dacryocystorhinostomy by preventing cicatricial changes of the ostium, especially
      in high-risk cases such as revision and post-traumatic dacryocystorhinostomy.

PMID- 24896778
TI  - [Revista Brasileira de Epidemiologia. Editorial].

PMID- 24896777
TI  - Clonal diversity and clone formation in the parthenogenetic Caucasian rock Lizard
      Darevskia dahli [corrected].
AB  - The all-female Caucasian rock lizard species Darevskia dahli and other
      parthenogenetic species of this genus reproduce normally via true
      parthenogenesis. Previously, the genetic diversity of this species was analyzed
      using allozymes, mitochondrial DNA, and DNA fingerprint markers. In the present
      study, variation at three microsatellite loci was studied in 111 specimens of D.
      dahli from five populations from Armenia, and new information regarding clonal
      diversity and clone formation in D. dahli was obtained that suggests a multiple
      hybridization origin. All individuals but one were heterozygous at the loci
      studied. Based on specific allele combinations, 11 genotypes were identified
      among the individuals studied. Individuals with the same genotypes formed
      distinct clonal lineages: one major clone was represented by 72 individuals, an
      intermediate clone was represented by 21 individuals, and nine other clones were
      rare and represented by one or several individuals. A new approach based on the
      detection and comparison of genotype-specific markers formed by combinations of
      parental-specific markers was developed and used to identify at least three
      hybridization founder events that resulted in the initial formation of one major
      and two rare clones. All other clones, including the intermediate and seven rare
      clones, probably arose through postformation microsatellite mutations of the
      major clone. This approach can be used to identify hybridization founder events
      and to study clone formation in other unisexual taxa.

PMID- 24896779
TI  - Elderly victims of falls seen by prehospital care: gender differences.
AB  - OBJECTIVE: To identify elderly who are victims of falls, according to gender, who
      received care from prehospital services of Maringa, Parana. METHODS: A cross
      sectional exploratory study carried out with 1,444 elderly patients who suffered
      falls in Maringa in the period from 2006 to 2008. Data were gathered from
      prehospital care services, typed and processed using the Epi Info 6.04d(r). The
      chi2 test was used to compare the falls in relation to gender (significance level
      = 0.05). RESULTS: The number of falls according to gender presented similar
      percentages, 51.0% for males and 49.0% for females. Significant differences
      between genders were observed regarding age (p < 0.001), presence of alcohol
      breath (p < 0.001), type of fall (p < 0.001), place of fall (p < 0.001),
      treatment at hospital (p = 0.023), number of injuries (p = 0.014), type of injury
      (p < 0.001) and injury location (p <0.001). CONCLUSION: These results show that
      falls happen differently among the elderly when considering gender. It highlights
      the importance of understanding these differences in detail and the circumstances
      in which the fall occurred, since this knowledge is key to plan preventive
      actions.

PMID- 24896781
TI  - Factors associated with providing social security benefits for traumatic brain
      injury resulting from occupational accidents.
AB  - INTRODUCTION: The Occupational Accident (OA) is considered to be an important
      public health problem in Brazil. Traumatic Brain Injury (TBI) is the most common
      among them. The TBI is associated with high morbidity and mortality rates among
      workers. OBJECTIVE: To identify factors associated with providing social security
      benefits for TBI due to occupational accidents according to the specific type of
      economic activity in Brazil, in 2009. METHODS: This is a cross-sectional study
      that was conducted with all workers who were part of the General Regime of Social
      Security (RGPS) of Brazil. Secondary data were obtained from the National
      Information System Benefit, from the Synchronized National Register of the
      Ministry of Finance and from the General Register of Employed and Unemployed
      Persons. Data were analyzed using the multiple logistic regression method.
      RESULTS: We analyzed 2,006 cases of social security benefits for traumatic brain
      injury due to Occupational Accident. Factors associated with the concession of
      the benefit according to the economic activity of the Company of the beneficiary
      were identified. Associations were found with sex, income and the region of the
      Company. CONCLUSION: Factors associated with the concession of social security
      benefits by TBI resulting from OA differ depending on the type of economic
      activity in the study. Understanding these factors may contribute to the planning
      of preventive policies.

PMID- 24896780
TI  - Heavy physical work and low back pain: the reality in urban cleaning.
AB  - Low back pain (LBP) is a major public health issue. There is lack of research on
      this disorder affecting urban cleaning workers. A cross-sectional study was
      conducted to describe the prevalence of LBP, occupational and extra-occupational
      characteristics, as well as associated factors in these workers. A census was
      performed with 624 workers in Salvador, Brazil, using a questionnaire
      administered by an interviewer in 2010. Cases of LBP were defined by reported
      symptoms of pain in the previous 12 months, lasting more than a week or with
      monthly minimum frequency, which led to restrictions at work or to seeking
      medical attention, or in cases when respondents had a severity score > 3 on a
      numerical scale from 0 to 5. Physical demands at work were measured on a
      numerical 6-point scale with 14 variables. Psychosocial demands were measured
      using the Job Content Questionnaire. Sociodemographic factors, lifestyle habits
      and domestic work were evaluated. Multiple logistic regression (LR) was used to
      identify factors associated with LBP, for which the prevalence was 37.0%. Among
      them, 62.8% of workers felt pain in the last 7 days. LBP was associated with
      longer working hours, flexion and trunk rotation, psychosocial demands, working
      directly in collection and low schooling. Dynamic work (walking, running) served
      as a protective factor. It was concluded that many workers develop their activity
      at the presence of pain. The results emphasize the need for preventive measures
      through multifactorial approach encompassing adaptations in physical environment
      and changes in work organization. 

PMID- 24896782
TI  - Prevalence and factors associated with nutritional deviations in women in the pre
      pregnancy phase in two municipalities of the State of Rio de Janeiro, Brazil.
AB  - OBJECTIVE: To assess the prevalence and potential factors associated with pre
      pregnancy nutritional status of women. METHODS: This is a cross-sectional study
      carried out between December 2007 and November 2008 with 1,535 women in the first
      trimester of pregnancy and randomly selected in health units of the Brazilian
      public health system (SUS) in the municipalities of Queimados and Petropolis in
      the State of Rio de Janeiro. The diagnosis of nutritional deviations was based on
      the Body Mass Index, according to the classification of the Institute of
      Medicine, and the following categories were obtained: underweight, normal weight,
      overweight and obesity. In the statistical analysis, the multinomial logistic
      regression model was used and an odds ratio and confidence interval of 95% were
      estimated. RESULTS: The sample included women between 13 and 45 years. The
      prevalence of underweight, overweight and obesity were 10, 18 and 11%,
      respectively. Women living in Queimados, adolescents, women who did not live with
      a partner and smokers had a higher proportion of low pre-pregnancy weight. There
      was an association between hypertension, overweight and obesity. Adolescents
      presented lower chance to overweight and obesity. Living in Queimados reduced the
      odds of overweight. CONCLUSION: The proportion of pre-pregnancy nutritional
      deviations was high, and recognizing factors that lead to them is very important
      for an early identification of women at nutritional risk, with view to
      interventions to reduce the adverse effects of malnutrition on maternal and child
      health.

PMID- 24896783
TI  - Identification of common content between the questionnaire of the Health Survey
      (ISA-SP) and the International Classification of Functionality, Disability, and
      Health.
AB  - The purpose of this paper was to identify the common contents between Sao Paulo's
      Health Survey Questionnaire (Physical Disability and Emotional Health Blocks) and
      the International Classification of Functionality, Disability, and Health. The
      first stage of the research consisted of the search for the modules of Sao
      Paulo's Health Survey, which addressed the issue of disability, and the passages
      about this theme were highlighted and inserted into a new file. In the second
      stage, the significant contents were extracted. In the last one, these contents
      were codified to the codes of the International Classification of Functionality,
      Disability, and Health by two independent researchers. For the descriptive
      statistical analysis, crude numbers, percentages, and simple frequencies were
      used. The degree of agreement between the two professionals was calculated using
      Kappa's coefficient and the confidence interval. The most common domains were
      those about functions and body structures and about activities and participation,
      in which the domain of environmental factors presented a lower frequency of
      approach. 

PMID- 24896785
TI  - Limited activity and social participation after hospital discharge from leprosy
      treatment in a hyperendemic area in North Brazil.
AB  - INTRODUCTION: Neural damages are among the main factors that contribute to
      physical disability in leprosy. Systematic monitoring using a broad physical,
      psychological and social approach is necessary. OBJECTIVE: The objective of this
      study was to characterize the limitation of activity and social participation and
      its correlation with disabilities and/or impairment in individuals after being
      discharged from a multidrug leprosy therapy. METHOD: A cross-sectional study
      conducted in Araguaina, state of Tocantins, which is a leprosy hyperendemic
      municipality. We included cases of patients who were discharged from treatment
      considered as cured from January 2004 to December 2009. We performed
      dermatological examination and applied the Screening Activity Limitation and
      Safety Awareness (SALSA) and social participation scales. RESULTS: We included
      282 individuals (mean age: 45.8 years old). The paucibacillary operational
      classification was more common (170; 60.3%). The eye-hand-foot score ranged from
      0 to 12 (mean: 0.7). A total of 84 (29.8%) individuals presented limited
      activity. A slight restriction in social participation occurred in 18 (6.3%)
      cases. There was a statistically significant correlation between activity
      limitation, age (r = 0.40; p < 0.0001) and degree of functional limitation (r =
      0.54; p < 0.0001), as well as of restricted social participation, activity
      limitation (r = 0.56, p < 0.0001) and functional limitations (r = 0.54, p <
      0.0001). CONCLUSION: Functional limitation due to leprosy had an impact on the
      conduct of activities and social participation after the discharge from a leprosy
      treatment. The association between Screening of Activity Limitation and Safety
      Awareness and participation scales will assist in designing evidence-based
      assistance measures.

PMID- 24896784
TI  - Is the negative evaluation of dental services among the Brazilian elderly
      population associated with the type of service?
AB  - This study aimed at identifying the prevalence of the negative evaluation of
      dental services among elderly Brazilians and at investigating whether the
      prevalence was higher among those using public or philanthropic provider services
      than among those paying privately or using private health plans. Additionally,
      factors associated with this negative assessment were identified. Interview and
      survey data were collected in the residences of participants by trained and
      calibrated examiners as part of a national epidemiological survey of oral health
      conditions of the Brazilian population in 2002/2003. The dependent variable was
      obtained in response to questions regarding whether the participant had ever used
      dental services, the frequency of use, and the quality of this service. Potential
      responses to the questions regarding the quality of service were very poor or
      poor, fair, and good or very good. The main independent variable was the system
      of health care used with potential responses being health plan or private,
      public, and philanthropic services. We conducted univariate (linear tendency chi2
      test) and multiple descriptive analyses, and the partial proportional Odds model
      for ordinal logistic regression. Among the elderly, 196 (3.7%) evaluated the
      provided services negatively (very poor or poor). Participants with the following
      responses were more likely to evaluate the services negatively: those who had
      used public or philanthropic services, men, those with higher education, the ones
      who had not received information about preventing dental problems, those who
      perceived pain in their teeth and gums in the last six months, and those who self
      reported their oral health and speech was poor. In conclusion, elderly Brazilian
      users of public and philanthropic services were more likely than users of private
      or insurance-based plans to evaluate their dental services negatively, regardless
      of the other investigated variables.

PMID- 24896786
TI  - Social representations of obstetricians and neonatologists about fetal and early
      neonatal death certificate in the city of Sao Paulo.
AB  - INTRODUCTION: The insatisfactory completeness of the variables in the Death
      Certificate (DC) makes it difficult to obtain specific perinatal mortality
      indicators. OBJECTIVE: To assess the social representation of physicians about
      the perinatal DC. METHODS: Twenty-five physicians were interviewed in 15
      hospitals in the city of Sao Paulo, in 2009. Qualitative analysis was performed
      with the Collective Subject Discourse technique. RESULTS: The DC is primarily
      considered according to its legal aspect. Physicians feel responsible for
      fulfilling the cause of death. The majority of them reported receiving help from
      other professionals to complete information on maternal characteristics and
      identification variables. There is lack of information on the mother's pre-natal
      conditions, which can make it difficult to identify the perinatal cause of death,
      mainly in the Unified Health System (SUS) hospitals. Some participants received
      specific DC training only when attending medical schools. CONCLUSIONS: The
      organization of medical work may affect the completion of the DC, especially in
      hospitals from SUS. Other professionals contributed to this task and their
      training can improve the quality of information.

PMID- 24896787
TI  - Investigation of ill-defined causes of death: assessment of a program's
      performance in a state from the Northeastern region of Brazil.
AB  - OBJECTIVE: The proportion of ill-defined causes of death (IDCD) was persistently
      high in some regions of Brazil in 2004. In 2005, the Brazilian government
      implemented a project in order to decrease this proportion, especially in higher
      priority states and municipalities. This study aimed to evaluate the performance
      of this project in Alagoas - a state from the Northeast region of Brazil. METHOD:
      We selected a probabilistic sample of 18 municipalities. For all IDCD identified
      in 2010, we collected the verbal autopsy (VA) questionnaires used for home
      investigation, and the Ministry of Health (MoH) form, which contains information
      about the final disease and cause of death taken from hospital records,
      autopsies, family health teams, and civil registry office records. The completion
      rate of the MoH form and VA was calculated using the number of deaths with
      specific causes assigned among investigated deaths. RESULTS: A total of 681 IDCD
      were recorded in 2010 in the sample, of which 26% had a MoH and/or VA3 forms
      completed. Although the majority of cases were attended by health professionals
      during the terminal disease, the completion rate was 45% using the MoH form and
      80% when VA was performed. CONCLUSIONS: Our findings provide evidence that the
      training of the epidemiological surveillance teams in the investigation and
      certification of causes of death could contribute to improve the quality of
      mortality data.

PMID- 24896788
TI  - Determinants of homicides in the state of Bahia, Brazil, in 2009.
AB  - PURPOSE: To carry out a study of association between socioeconomic and
      demographic factors and homicides in general population, in the state of Bahia,
      in 2009. METHODS: This is an ecological study. The data were collected from the
      database of the Information System about Mortality of the Ministry of Health,
      from the Brazilian Institute of Geography and Statistics and the Institute of
      Applied Economic Research. The Global Moran index was calculated for the
      detection of spatial autocorrelation, and the Local Moran index was calculated
      for the detection of spatial Clusters. The transformation in the variable answer
      (homicides rates) was performed and it was shaped using the Conditional
      Autoregressive Model. RESULTS: The data showed spatial autocorrelation. Two
      clusters of municipalities with high rates of homicides were identified, one
      located predominantly in the Greater Metropolitan Region of Salvador and the
      other in the South Region of Bahia, especially Eunapolis and Lauro de Freitas,
      which had the highest rates. The Average Residents Variables, local GDP and the
      Percentage of Illiteracy presented an inverse association with homicide rates,
      and the variables Firjan's municipal development index of work and income.
      Enrolment in high school and the Average of Bolsa Familia were directly
      associated. CONCLUSIONS: The urbanization process, in most cases, not controlled
      by the State, in most cases, made the cities bigger and with better socioeconomic
      conditions, attraction centers for people with different socioeconomic levels,
      increasing the social inequality among the residents of these regions, with
      parallel increase in homicide rates.

PMID- 24896789
TI  - EpiFloripa Health Survey: the methodological and operational aspects behind the
      scenes.
AB  - The present study aims at describing the sampling plan, operational aspects and
      strategies used to optimize the field work of a cross-sectional, population-based
      study conducted in a southern capital of Brazil. For this purpose, the sample
      design, data collection instrument, selection of interviewers, pilot study, data
      collection, field logistics, quality control, consistency control, costs, and
      divulgation of results are herein described. The study's response rate was 85.3%.
      We found that the comparison of frequency measurements with and without self
      assessment had no significant impact on the estimates, and that the design
      effect, estimated at 2, was sufficient for most calculations. The reproducibility
      of the questionnaire was satisfactory, with Kappa values and intraclass
      correlation coefficients ranging from 0.6 to 0.9. The strategies used to overcome
      operational problems, such as counting of households, use of maps, questionnaire
      structuring, rigorous organization of the field work and monitoring of the
      estimates were fundamental in conducting the study. 

PMID- 24896790
TI  - Vigitel--Aracaju, Sergipe, 2008: the effects of post-stratification adjustments
      in correcting biases due to the small amount of households with a landline
      telephone.
AB  - INTRODUCTION: The Telephone Survey has several attractions, such as low
      operational costs and speed the process, when compared to the Household Survey.
      However, the exclusion of house holds without a landline phone canpose a serious
      question of the valid it yof the estimates. OBJECTIVE: Evaluating the use of post
      stratification adjustments to correct the potential biasdue to low coverage of
      landline phonein the results published in the Vigitel system. METHODS: We
      compared the prevalence obtained by the Household Survey and the Vigitel, in
      Aracaju, Sergipe, where 49% of households had a telephone, calculating the
      differences measured between the surveys thatused the square root mean square
      error as a measure of accuracy of the estimate. RESULTS: The Household Survey
      showed ten variables associated with landline phone. From this set of variables,
      post stratification weights corrected the potential bias of the consumption of
      beans in five or more days per week, vegetables intake regularly and recommended
      self-assessment of health as bad and morbidity of diabetes,while the weights
      partially eliminated the bias of the prevalence of asthma, possession of health
      insurance coverage and prevention of breast cancer in women aged 50 to 59 years.
      CONCLUSIONS: In order to reduce the potential bias in the results published by
      Vigitel system, in areas with low telephone coverage, it becomes necessary to use
      alternative weighting procedures and selection strategy of external variables for
      construction of post-stratification weights.

PMID- 24896791
TI  - Profile of patients with lung cancer assisted at the National Cancer Institute,
      according to their smoking status, from 2000 to 2007.
AB  - INTRODUCTION: Tobacco use is directly related to the future incidence of lung
      cancer. In Brazil, a growing tendency in age-adjusted lung cancer mortality rates
      was observed in recent years. OBJECTIVE: To describe the profile of patients with
      lung cancer diagnosed and treated at the National Cancer Institute (INCA) in Rio
      de Janeiro, Brazil, between 2000 and 2007 according to their smoking status.
      METHODS: An observational study was conducted using INCA's database of cancer
      cases. To assess whether the observed differences among the categories of
      sociodemographic variables, characterization of the tumor, and assistance -
      pertaining to smokers and non-smokers - were statistically significant, a chi
      square test was applied. A multiple correspondence analysis was carried out to
      identify the main characteristics of smokers and non-smokers. RESULTS: There was
      a prevalence of smokers (90.5% of 1131 patients included in the study). The first
      two dimensions of the multivariate analysis explained 72.8% of data variability.
      Four groups of patients were identified, namely smokers, non-smokers, small-cell
      tumors, and tumors in early stages. CONCLUSION: Smoking cessation must be
      stimulated in a disseminated manner in the population in order to avoid new cases
      of lung cancer. The Tumors in Initial Stages Group stood out with greater chances
      of cure.

PMID- 24896792
TI  - Socioeconomic profile of the elderly in Florianopolis: comparative analysis
      studies Perfil do Idoso 2002 and EpiFloripa Idoso 2009.
AB  - OBJECTIVE: The aim of this study is to compare the socioeconomic profile of the
      population aged 60 or older living in Florianopolis in 2002 and 2009. METHODS:
      Data were obtained through the studies Perfil do Idoso 2002 and EpiFloripa Idoso
      2009 based on household surveys. RESULTS: There was a predominance of aged 60 to
      69 years old, married and living with spouse and children. There was a
      significant improvement in the level of education and, on the economic aspects,
      retirement remains the main source of income, increasing the number of families
      receiving no more than three minimum wages and reducing those with monthly income
      above 10 minimum wages. The number of older adults who considers their current
      financial situation better than age 50 increased as the proportion of subjects
      with fair/poor self-perception health. It was also highlighted greater purchasing
      private health insurance. CONCLUSION: Comparison of the two studies presented
      here can support the actions of managers in order to bring effective results to
      the population.

PMID- 24896793
TI  - Clinical management of the induction of labor in intrauterine fetal death:
      evaluation of incidence of cesarean section and related conditions.
AB  - OBJECTIVE: To assess the incidence and conditions associated with cesarean
      section in a cohort of pregnant women with intrauterine fetal death (IUFD), and
      clinical management to anticipate the childbirth. METHODS: It was a retrospective
      cohort study with 163 mothers with IUFD, at the second half of pregnancy, who
      were managed to anticipate childbirth using pharmacological preparations and/or a
      mechanical method (Foley catheter) in a teaching hospital in Rio de Janeiro
      State, Brazil. Cox regression was used to evaluate the effect of the clinical
      methods on the kind of delivery. RESULTS: The Subgroups A (misoprostol or
      Oxytocin), B (misoprostol and Oxytocin), and C (Foley catheter alone or combined
      with misoprostol and/or Oxytocin) were formed according to the applied methods.
      Nine out of 163 cases ended with cesarean section. The incidence of cesarean
      section was 3.5 per 1,000 people-hours, meaning that a pregnant woman with IUFD
      had a 15.6% risk of cesarean section during the first 48 hours of clinical
      management to anticipate childbirth. The conditions significantly associated with
      the mode of delivery were placental abruption (HR: 44.97), having two or more
      previous cesarean deliveries (HR: 10.03), and mechanical method with Foley
      catheter (HR: 5.01). CONCLUSION: Cesarean section was an essential conduct in
      this cohort and followed previous cesarean delivery and placental abruption. The
      effect of the mechanical method on the abdominal route suggests that the Foley
      catheter method was used in the most difficult cases and that the surgery was
      performed to ensure maternal health.

PMID- 24896794
TI  - Directionality of physical and psychological dating violence among adolescents in
      Recife, Brazil.
AB  - OBJECTIVE: The aim was to investigate the physical and psychological dating
      violence among adolescents with respect to the profiles of directionality - only
      man perpetrates, only woman perpetrates, and bidirectional, ie, both perpetrate
      violence. METHODS: Sample was performed by two-stage cluster selection in public
      and private school in the city of Recife (PE), Brazil, presenting data on 355
      adolescents of both sexes between 15 and 19 years old. Psychological violence was
      measured in dimensions threat, verbal/emotional, and relational. Statistical
      analyzes incorporated the sampling weight and the complex sample design. RESULTS:
      Violence is bidirectional in most forms studied (83.9%) and girls reported higher
      levels of perpetration of physical violence, and boys reported more perpetration
      of relational violence. CONCLUSION: It was concluded that adolescent dating
      violence shows a pattern where partners attack each other, both physically and
      psychologically. Future research should study the patterns of these acts of
      violence, keeping the adolescent couple as the unit of analysis and exploring the
      context in which such violence occurs.

PMID- 24896795
TI  - Social support and common mental disorder among medical students.
AB  - INTRODUCTION: Different kinds of psychological distress have been identified for
      students in the health field, especially in the medical school. OBJECTIVE: To
      estimate the prevalence of mental suffering among medical students in the
      Southeastern Brazil and asses its association with social support. METHODS: It is
      a cross-sectional study. Structured questionnaires were applied for students from
      the 1st up to the 6th years of the medical school of Universidade Estadual
      Paulista "Julio de Mesquita Filho", assessing demographic variables related to
      aspects of graduation and adaptation to the city. Psychological suffering was
      defined as a common mental disorder (CMD) assessed by the Self Reporting
      Questionnaire (SRQ-20). Social support was assessed by the social support scale
      of the Medical Outcomes Study (MOS). The association between the outcome and
      explanatory variables was assessed by the chi2 test and Logistic Regression, for
      the multivariate analyses, using p < 0.05. RESULTS: The response rate was of
      80.7%, with no differences between sample and the population regarding gender (p
      = 0.78). The average age was 22 years old (standard deviation - SD = 2.2), mainly
      women (58.2%) and students who were living with friends (62%). The prevalence of
      CMD was 44.9% (95%CI 40.2 - 49.6). After the multivariate analyses, the
      explanatory variables that were associated with CMD were: feeling rejected in the
      past year (p < 0.001), thinking about leaving medical school (p < 0.001) and
      "interaction" in the MOS scale (p = 0.002). CONCLUSIONS: The prevalence of CMD
      among medical students was high and insufficient social support was an important
      risk factor. Our findings suggest that interventions to improve social
      interaction among those students could be beneficial, decreasing the prevalence
      of CMD in this group.

PMID- 24896796
TI  - Diagnostic accuracy of anthropometric indices in predicting excess body fat among
      seven to ten-year-old children.
AB  - PURPOSE: To evaluate the accuracy of the body mass index (BMI), waist
      circumference (WC) and waist-to-height ratio (WHtR) in detecting excess body fat
      among schoolchildren in Florianopolis, Santa Catarina. METHODS: Cross-sectional
      study with 2,772 schoolchildren aged seven to ten years. Receiver Operating
      Characteristic (ROC) curves were used to compare the diagnostic accuracy of the
      BMI, the WC and the WHtR in identifying children with excess body fat (defined as
      values that were equal to or higher than the 90th percentile of the standardized
      residuals obtained from the sum of the four skinfolds thickness). Likelihood
      ratio estimates were used to select, for each anthropometric index, the cut-off
      points that presented the highest association with excess body fat. RESULTS: The
      BMI, WC and WHtR performed well in detecting excess body fat, indicated by areas
      under the ROC curve (AUC) close to 1.0, with slightly higher AUC for the BMI in
      comparison to the WC and the WHtR concerning both sexes. Highly sensitive and
      specific cut-off points were derived for the three anthropometric indices.
      Sensitivity ranged from 85.7 to 92.9% for the BMI, from 78.6 to 89.7% for the WC,
      and from 78.6 to 89.2% for the WHtR. Specificity ranged from 83.2 to 91.4%, from
      75.0 to 90.7%, and from 77.4 to 88.3% for the BMI, the WC and the WHtR,
      respectively. CONCLUSION: BMI, WC and WHtR can be used as diagnostic tests to
      identify excess body fat in children from seven to ten years of age.

PMID- 24896797
TI  - Epidemiological aspects of pulmonary tuberculosis in Mato Grosso do Sul, Brazil.
AB  - OBJECTIVE: To describe the profile and analyze the cases of pulmonary
      tuberculosis reported in the state of Mato Grosso do Sul from 2001 to 2009,
      according to the chosen variable categories (gender, age, ethnicity, education,
      residing in the border area, indigenous population and individuals deprived of
      liberty). METHODS: An ecological study was conducted from data of reported cases
      of TB. RESULTS: Estimates of risk higher than the general population, and even
      extremely high, were obtained in three specific populations, which certainly
      requires priority attention from health policies and health network professionals
      to keep the transmission of tuberculosis under control, including in the
      population residing in the borders with Bolivia and Paraguay, the indigenous
      population and individuals deprived of liberty. CONCLUSIONS: This study sought to
      show the importance of discussing territoriality more adequately in Brazil. A
      continuous reevaluation of all health programs is needed for populations in each
      of the areas where they live. Then, it will be possible to correct the incidence
      rate of tuberculosis for specific populations in the state, taking into account
      populations in each place of residence and considering their specificities and
      differences. In conclusion, in the light of the present study, it is necessary to
      discuss more efficient strategies to control tuberculosis in the various
      territories of the state of Mato Grosso do Sul if we actually want to minimize
      this endemic to acceptable levels in our environment.

PMID- 24896798
TI  - Factors associated with the feeding practices of the adult population of Goiania,
      Goias, Brazil.
AB  - This cross-sectional study identified the factors associated with adult feeding
      practices in Goiania, the capital of the state of Goias, in the Midwestern region
      of Brazil, by means of telephone interviews with 2,002 adults (> 18 years old).
      Information about demographic aspects, lifestyle, nutritional status, and food
      consumption was collected, leading to a sum of healthy food choices. It was
      observed that men and women have an average of two healthy food choices and low
      frequency of fruit intake (5.4% of men; 8.5% of women), as well as the
      consumption of legumes and vegetables (18.1% of men; 22.6% of women). The
      hierarchical multiple regression analysis revealed that the mean healthy food
      choice among men increases with age and physical practice, and among women, with
      paid work. The prevalence of unhealthy food choices associated with other risk
      behaviors favors the development of chronic diseases. Multi-strategy and
      intersectorial actions are necessary to overcome this situation. 

PMID- 24896799
TI  - [The oral health studies in the Pelotas birth cohort studies, RS, Brazil].

PMID- 24896800
TI  - GO-COO-HP-beta-CD nanosphere: a complex construction and its drug-loading
      properties.
AB  - A novel nanosphere based on carboxylated GO (GO-COOH) and hydroxypropyl-beta-CD
      (HP-beta-CD) was synthesized to construct a complex of GO-COO-HP-beta-CD. The
      complex formation process was studied using spectral characterization and
      transmission electron microscopy (TEM). X-ray diffraction and energy dispersive
      spectroscopy patterns show that HP-beta-CD molecules either cover or intercalate
      into GO-COOH interlayers in the complex. Fourier transform infrared spectroscopy
      results indicate that GO-COOH and HP-beta-CD are linked with covalent bonds
      formed via esterification. When employed as nanohybrid drug carriers for
      dexamethasone, the inclusion displays good dispersibility validated by dynamic
      light scattering (DLS). Cytotoxicity assays and hemolysis testing demonstrate
      that the nanospheres possess good biological compatibility. The loading capacity
      of dexamethasone is as high as 32.33%, with loading efficiency 64.66%. 

PMID- 24896801
TI  - Gender gap in lipid management amongst diabetes population: an observation.
AB  - Studies have consistently demonstrated that women with diabetes are more likely
      than men to have a LDL-C above treatment goals. However, this pattern of gender
      gap has not been observed in many studies for HgbA1c goal attainment. Although
      the reasons for this are not fully understood, intolerance to statin therapy in
      women due to differences in pharmacodynamics and pharmacokinetics may play a role
      as female sex and aging has been associated with statin-associated myopathy. The
      concept of gender gap is useful for identifying at-risk groups for prevention and
      treatment efforts. 

PMID- 24896802
TI  - Decline in locomotor functions over time in HIV-infected patients.

PMID- 24896803
TI  - Research on oral pre-exposure prophylaxis in sub-Saharan Africa is an example of
      biomedical tunnel vision.

PMID- 24896804
TI  - Acute renal failure and liver toxicity in an HIV/hepatitis C coinfected patient
      receiving telaprevir and boosted atazanavir.

PMID- 24896806
TI  - Does pregnancy affect the pharmacokinetics of efavirenz?

PMID- 24896805
TI  - Prevention of HIV-1 transmission with postexposure prophylaxis after inadvertent
      infected blood transfusion.

PMID- 24896807
TI  - Kre-Celazine((r)) as a viable treatment for juvenile rheumatoid
      arthritis/juvenile idiopathic arthritis - a pilot study.
AB  - The purpose of this study was to ascertain whether an oral, non-prescription,
      nutritional supplement compound composed of a proprietary alkali-buffered
      creatine monohydrate and cetylated fatty acids mixture (Kre-Celazine((r))) was
      efficacious in reducing or eliminating refractory pain and inflammation, without
      untoward effects, in Juvenile Rheumatoid Arthritis (JRA), which is also called
      Juvenile Idiopathic Arthritis (JIA). JRA/JIA is a patho-physiologically complex,
      chronic childhood autoimmune inflammatory disease of unknown etiology. Numerous
      studies have unsuccessfully attempted to pinpoint a possible common initiation
      event. Officially considered an affliction of children below the age of 16 years,
      an initial diagnosis has been confirmed in infants less than 1 year old, to
      individuals older then 17 years. In this study, sixteen juveniles, ages 7 through
      16 years, experiencing long-standing, unremitting pain and inflammation despite
      previous use of prescription anti-inflammatory drugs and NSAIDs, were enrolled in
      a 30-day, open-label clinical study and treated with Kre-Celazine. Efficacy of
      this nutritional supplement was determined by the juvenile's personal physician
      and based on observations of the following: (1) significant reduction or
      elimination of palpable signs of inflammation; (2) renormalization of range of
      motion; (3) reduction or absence of perceived pain as reported to the physician
      by the patient; (4) renormalization of C-reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR) values. In addition, the individual's previous steroid
      or non-steroidal anti-inflamatory medication(s) were reduced or eliminated in a
      stepwise progressive fashion during the study.

PMID- 24896808
TI  - 23,24-Dihydrocucurbitacin C: a new compound regarded as the next metabolite of
      cucurbitacin C.
AB  - Cucurbitacin C, a bitter substance in Cucumis sativus L., was isolated from green
      leaves by using phytochemical methods. An analytical method using high
      performance liquid chromatography (HPLC) was established for the quantification
      of cucurbitacin C in different parts of the cucumber plant at different growth
      periods. Cucurbitacin C was detected in the leaves and stems but not in the
      female flowers, fruits, roots and leafstalks. The level of cucurbitacin C
      decreased significantly with the process of young leaves turning old. A new
      compound named 23,24-dihydrocucurbitacin C, regarded as the next metabolite of
      cucurbitacin C, was determined unambiguously by HPLC-quadrupole-time-of-flight
      mass spectrometry and nuclear magnetic resonance.

PMID- 24896809
TI  - Robin Holliday 1932-2014.

PMID- 24896810
TI  - It takes two to tangle: Prp24 and spliceosome assembly.

PMID- 24896811
TI  - The subtle allostery of microtubule dynamics.

PMID- 24896813
TI  - Physico-chemical quality parameters of herbal products from Agave sisalana.
AB  - Agave sisalana components have great potential in different pharmaceutical
      applications, but the quality of herbal raw materials is essential to reach the
      desired product specifications. In this work, we investigated the physico
      chemical quality parameters of bole and wastes from decortication of A. sisalana
      leaves. The statistically significant variations among products suggest different
      pharmaceutical applications for each of them. 

PMID- 24896812
TI  - Endothelial depletion of Acvrl1 in mice leads to arteriovenous malformations
      associated with reduced endoglin expression.
AB  - Rare inherited cardiovascular diseases are frequently caused by mutations in
      genes that are essential for the formation and/or function of the
      cardiovasculature. Hereditary Haemorrhagic Telangiectasia is a familial disease
      of this type. The majority of patients carry mutations in either Endoglin (ENG)
      or ACVRL1 (also known as ALK1) genes, and the disease is characterized by
      arteriovenous malformations and persistent haemorrhage. ENG and ACVRL1 encode
      receptors for the TGFbeta superfamily of ligands, that are essential for
      angiogenesis in early development but their roles are not fully understood. Our
      goal was to examine the role of Acvrl1 in vascular endothelial cells during
      vascular development and to determine whether loss of endothelial Acvrl1 leads to
      arteriovenous malformations. Acvrl1 was depleted in endothelial cells either in
      early postnatal life or in adult mice. Using the neonatal retinal plexus to
      examine angiogenesis, we observed that loss of endothelial Acvrl1 led to venous
      enlargement, vascular hyperbranching and arteriovenous malformations. These
      phenotypes were associated with loss of arterial Jag1 expression, decreased
      pSmad1/5/8 activity and increased endothelial cell proliferation. We found that
      Endoglin was markedly down-regulated in Acvrl1-depleted ECs showing endoglin
      expression to be downstream of Acvrl1 signalling in vivo. Endothelial-specific
      depletion of Acvrl1 in pups also led to pulmonary haemorrhage, but in adult mice
      resulted in caecal haemorrhage and fatal anaemia. We conclude that during
      development, endothelial Acvrl1 plays an essential role to regulate endothelial
      cell proliferation and arterial identity during angiogenesis, whilst in adult
      life endothelial Acvrl1 is required to maintain vascular integrity. 

PMID- 24896814
TI  - DNA barcoding and the associated PhylAphidB@se website for the identification of
      European aphids (Insecta: Hemiptera: Aphididae).
AB  - Aphids constitute a diverse group of plant-feeding insects and are among the most
      important crop pests in temperate regions. Their morphological identification is
      time-consuming and requires specific knowledge, training and skills that may take
      years to acquire. We assessed the advantages and limits of DNA barcoding with the
      standard COI barcode fragment for the identification of European aphids. We
      constructed a large reference dataset of barcodes from 1020 specimens belonging
      to 274 species and 87 genera sampled throughout Europe and set up a database
      driven website allowing species identification from query sequences. RESULTS: In
      this unbiased sampling of the taxonomic diversity of European aphids,
      intraspecific divergence ranged from 0.0% to 3.9%, with a mean value of 0.29%,
      whereas mean congeneric divergence was 6.4%, ranging from 0.0% to 15%. Neighbor
      joining analysis generated a tree in which most species clustered in distinct
      genetic units. Most of the species with undifferentiated or overlapping barcodes
      belonged to the genus Aphis or, to a lesser extent, the genera Brachycaudus,
      Dysaphis and Macrosiphum. The taxa involved were always morphologically similar
      or closely related and belonged to species groups known to present taxonomic
      difficulties. CONCLUSIONS: These data confirm that COI barcoding is a useful
      identification tool for aphids. Barcode identification is straightforward and
      reliable for 80% of species, including some difficult to distinguish on the basis
      of morphological characters alone. Unsurprisingly, barcodes often failed to
      distinguish between species from groups for which classical taxonomy has also
      reached its limits, leading to endless revisions and discussions about species
      and subspecies definitions. In such cases, the development of an effective
      procedure for the accurate identification of aphid specimens continues to pose a
      difficult challenge.

PMID- 24896816
TI  - Restoring trust in VA health care.

PMID- 24896815
TI  - Effect of female genital schistosomiasis and anti-schistosomal treatment on
      monocytes, CD4+ T-cells and CCR5 expression in the female genital tract.
AB  - BACKGROUND: Schistosoma haematobium is a waterborne parasite that may cause
      female genital schistosomiasis (FGS), characterized by genital mucosal lesions.
      There is clinical and epidemiological evidence for a relationship between FGS and
      HIV. We investigated the impact of FGS on HIV target cell density and expression
      of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore
      we evaluated the effect of anti-schistosomal treatment on these cell populations.
      DESIGN: The study followed a case-control design with post treatment follow-up,
      nested in an on-going field study on FGS. METHODS: Blood and cervical cytobrush
      samples were collected from FGS negative and positive women for flow cytometry
      analyses. Urine samples were investigated for schistosome ova by microscopy and
      polymerase chain reaction (PCR). RESULTS: FGS was associated with a higher
      frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p
      = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples
      from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell
      population decreased significantly in both compartments after anti-schistosomal
      treatment (p = 0.043). Although the frequency of CD4+ cells did not change after
      treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly
      in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to
      5.6% in genital samples, p = 0.025). CONCLUSIONS: The results support the
      hypothesis that FGS may increase the risk of HIV acquisition, not only through
      damage of the mucosal epithelial barrier, but also by affecting HIV target cell
      populations, and that anti-schistosomal treatment can modify this.

PMID- 24896817
TI  - Evidence for camel-to-human transmission of MERS coronavirus.
AB  - We describe the isolation and sequencing of Middle East respiratory syndrome
      coronavirus (MERS-CoV) obtained from a dromedary camel and from a patient who
      died of laboratory-confirmed MERS-CoV infection after close contact with camels
      that had rhinorrhea. Nasal swabs collected from the patient and from one of his
      nine camels were positive for MERS-CoV RNA. In addition, MERS-CoV was isolated
      from the patient and the camel. The full genome sequences of the two isolates
      were identical. Serologic data indicated that MERS-CoV was circulating in the
      camels but not in the patient before the human infection occurred. These data
      suggest that this fatal case of human MERS-CoV infection was transmitted through
      close contact with an infected camel. 

PMID- 24896818
TI  - Naloxegol for opioid-induced constipation in patients with noncancer pain.
AB  - BACKGROUND: Opioid-induced constipation is common and debilitating. We
      investigated the efficacy and safety of naloxegol, an oral, peripherally acting,
      MU-opioid receptor antagonist, for the treatment of opioid-induced constipation.
      METHODS: In two identical phase 3, double-blind studies (study 04, 652
      participants; study 05, 700 participants), outpatients with noncancer pain and
      opioid-induced constipation were randomly assigned to receive a daily dose of
      12.5 or 25 mg of naloxegol or placebo. The primary end point was the 12-week
      response rate (>=3 spontaneous bowel movements per week and an increase from
      baseline of >=1 spontaneous bowel movements for >=9 of 12 weeks and for >=3 of
      the final 4 weeks) in the intention-to-treat population. The key secondary end
      points were the response rate in the subpopulation of patients with an inadequate
      response to laxatives before enrollment, time to first postdose spontaneous bowel
      movement, and mean number of days per week with one or more spontaneous bowel
      movements. RESULTS: Response rates were significantly higher with 25 mg of
      naloxegol than with placebo (intention-to-treat population: study 04, 44.4% vs.
      29.4%, P=0.001; study 05, 39.7% vs. 29.3%, P=0.02; patients with an inadequate
      response to laxatives: study 04, 48.7% vs. 28.8%, P=0.002; study 05, 46.8% vs.
      31.4%, P=0.01); in study 04, response rates were also higher in the group treated
      with 12.5 mg of naloxegol (intention-to-treat population, 40.8% vs. 29.4%,
      P=0.02; patients with an inadequate response to laxatives, 42.6% vs. 28.8%,
      P=0.03). A shorter time to the first postdose spontaneous bowel movement and a
      higher mean number of days per week with one or more spontaneous bowel movements
      were observed with 25 mg of naloxegol versus placebo in both studies (P<0.001)
      and with 12.5 mg of naloxegol in study 04 (P<0.001). Pain scores and daily opioid
      dose were similar among the three groups. Adverse events (primarily
      gastrointestinal) occurred most frequently in the groups treated with 25 mg of
      naloxegol. CONCLUSIONS: Treatment with naloxegol, as compared with placebo,
      resulted in a significantly higher rate of treatment response, without reducing
      opioid-mediated analgesia. (Funded by AstraZeneca; KODIAC-04 and KODIAC-05
      ClinicalTrials.gov numbers, NCT01309841 and NCT01323790, respectively.).

PMID- 24896820
TI  - Improving health care for veterans--a watershed moment for the VA.

PMID- 24896821
TI  - My hidden VA list.

PMID- 24896819
TI  - Actionable diagnosis of neuroleptospirosis by next-generation sequencing.
AB  - A 14-year-old boy with severe combined immunodeficiency presented three times to
      a medical facility over a period of 4 months with fever and headache that
      progressed to hydrocephalus and status epilepticus necessitating a medically
      induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased
      next-generation sequencing of the cerebrospinal fluid identified 475 of 3,063,784
      sequence reads (0.016%) corresponding to leptospira infection. Clinical assays
      for leptospirosis were negative. Targeted antimicrobial agents were administered,
      and the patient was discharged home 32 days later with a status close to his
      premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the
      Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence
      of Leptospira santarosai infection. 

PMID- 24896822
TI  - Molecular and phenotypic data support the recognition of the Wakatobi
      Flowerpecker (Dicaeum kuehni) from the unique and understudied Sulawesi region.
AB  - Accurate estimates of species richness are essential to macroecological and
      macroevolutionary research, as well as to the effective management and
      conservation of biodiversity. The resolution of taxonomic relationships is
      therefore of vital importance. While molecular methods have revolutionised
      taxonomy, contemporary species delimitation requires an integrative, multi
      disciplinary approach. Despite boasting a remarkably high level of endemism, the
      avifauna of the Sulawesi region of Indonesia remains poorly studied. Previous
      studies of avian diversity in Sulawesi have focussed predominantly on phenotypic
      characteristics, thus potentially overlooking any genetically distinct lineages.
      Grey-sided Flowerpecker Dicaeum celebicum populations from the Wakatobi
      archipelago were originally described as a separate species from those on nearby
      mainland Sulawesi. However, for reasons that remain unknown, the Wakatobi
      populations were reclassified as a subspecies of the mainland form. Combining
      estimates of genetic divergence with phylogenetic and morphological analyses, we
      reassessed the status of Wakatobi populations. Our results describe the Wakatobi
      populations as a separate species to those on mainland Sulawesi; reproductively
      isolated, genetically and morphologically distinct. We therefore recommend the
      reclassification of these populations to their original status of Dicaeum kuehni
      and propose the vernacular name 'Wakatobi Flowerpecker'. In consideration of our
      findings and the lack of integrative ornithological research within the Sulawesi
      region, we believe species richness and avian endemism within the region are
      underestimated. 

PMID- 24896823
TI  - CXCR7 controls competition for recruitment of beta-arrestin 2 in cells expressing
      both CXCR4 and CXCR7.
AB  - Chemokine CXCL12 promotes growth and metastasis of more than 20 different human
      cancers, as well as pathogenesis of other common diseases. CXCL12 binds two
      different receptors, CXCR4 and CXCR7, both of which recruit and signal through
      the cytosolic adapter protein beta-arrestin 2. Differences in CXCL12-dependent
      recruitment of beta-arrestin 2 in cells expressing one or both receptors remain
      poorly defined. To quantitatively investigate parameters controlling association
      of beta-arrestin 2 with CXCR4 or CXCR7 in cells co-expressing both receptors, we
      used a systems biology approach combining real-time, multi-spectral luciferase
      complementation imaging with computational modeling. Cells expressing only CXCR4
      maintain low basal association with beta-arrestin 2, and CXCL12 induces a rapid,
      transient increase in this interaction. In contrast, cells expressing only CXCR7
      have higher basal association with beta-arrestin 2 and exhibit more gradual,
      prolonged recruitment of beta-arrestin 2 in response to CXCL12. We developed and
      fit a data-driven computational model for association of either CXCR4 or CXCR7
      with beta-arrestin 2 in cells expressing only one type of receptor. We then
      experimentally validated model predictions that co-expression of CXCR4 and CXCR7
      on the same cell substantially decreases both the magnitude and duration of
      CXCL12-regulated recruitment of beta-arrestin 2 to CXCR4. Co-expression of both
      receptors on the same cell only minimally alters recruitment of beta-arrestin 2
      to CXCR7. In silico experiments also identified beta-arrestin 2 as a limiting
      factor in cells expressing both receptors, establishing that CXCR7 wins the
      "competition" with CXCR4 for CXCL12 and recruitment of beta-arrestin 2. These
      results reveal how competition for beta-arrestin 2 controls integrated responses
      to CXCL12 in cells expressing both CXCR4 and CXCR7. These results advance
      understanding of normal and pathologic functions of CXCL12, which is critical for
      developing effective strategies to target these pathways therapeutically. 

PMID- 24896824
TI  - Clinical effect of surgical correction for nasal pathology on the treatment of
      obstructive sleep apnea syndrome.
AB  - OBJECTIVES: This study aimed to evaluate the hypothesis that relief of nasal
      obstruction in subjects with obstructive sleep apnea (OSA) would lead to reduce
      OSA severity and to discuss the available evidence on the clinical efficacy of
      nasal surgery as a treatment modality for OSA. STUDY DESIGN: Twenty-five subjects
      who had reduced patency of nasal cavity and narrowing of retroglossal or
      retropalatal airways were diagnosed with OSA and underwent nasal surgery, such as
      septoplasty or turbinoplasty to correct nasal pathologies. The effect of the
      surgery on nasal patency was quantified by measuring minimal cross-sectional area
      (MCA) using acoustic rhinometry. The watch-PAT-derived respiratory disturbance
      index (RDI), apnea and hypopnea index (AHI), lowest oxygen saturation, and valid
      sleep time were measured before and after nasal surgery. RESULTS: The present
      study shows that the AHI and RDI decreased significantly and the lowest oxygen
      saturation and valid sleep time rose after nasal surgery in 25 OSA subjects. In
      addition, a reduction in subjective symptoms was observed in subjects and mean
      MCA increased after nasal surgery. Fourteen subjects were classified as
      responders and 11 subjects as non-responders. Responders showed considerable
      improvement of their subjective symptoms and the AHI and RDI were significantly
      lower after surgery. We found that the changes between pre- and post-operative
      AHI and RDI values were minimal in 11 non-responders. However, daytime somnolence
      and REM sleep time improved after nasal surgery in non-responders. CONCLUSIONS:
      Our study provides evidence that the surgical treatment of nasal pathology
      improves nasal airway patency and reduces OSA severity in 56% subjects.
      Furthermore, correction of nasal pathology appears to result in improved sleep
      quality in both responder and non-responders OSA subjects.

PMID- 24896825
TI  - Detecting selection in the blue crab, Callinectes sapidus, using DNA sequence
      data from multiple nuclear protein-coding genes.
AB  - The identification of genes involved in the adaptive evolution of non-model
      organisms with uncharacterized genomes constitutes a major challenge. This study
      employed a rigorous and targeted candidate gene approach to test for positive
      selection on protein-coding genes of the blue crab, Callinectes sapidus. Four
      genes with putative roles in physiological adaptation to environmental stress
      were chosen as candidates. A fifth gene not expected to play a role in
      environmental adaptation was used as a control. Large samples (n>800) of DNA
      sequences from C. sapidus were used in tests of selective neutrality based on
      sequence polymorphisms. In combination with these, sequences from the congener C.
      similis were used in neutrality tests based on interspecific divergence. In
      multiple tests, significant departures from neutral expectations and indicative
      of positive selection were found for the candidate gene trehalose 6-phosphate
      synthase (tps). These departures could not be explained by any of the historical
      population expansion or bottleneck scenarios that were evaluated in coalescent
      simulations. Evidence was also found for balancing selection at ATP-synthase
      subunit 9 (atps) using a maximum likelihood version of the Hudson, Kreitmen, and
      Aguade test, and positive selection favoring amino acid replacements within
      ATP/ADP translocase (ant) was detected using the McDonald-Kreitman test. In
      contrast, test statistics for the control gene, ribosomal protein L12 (rpl),
      which presumably has experienced the same demographic effects as the candidate
      loci, were not significantly different from neutral expectations and could
      readily be explained by demographic effects. Together, these findings demonstrate
      the utility of the candidate gene approach for investigating adaptation at the
      molecular level in a marine invertebrate for which extensive genomic resources
      are not available. 

PMID- 24896826
TI  - Long-term molecular epidemiology of Staphylococcus epidermidis blood culture
      isolates from patients with hematological malignancies.
AB  - Staphylococcus epidermidis is an important cause of bloodstream infections in
      patients with hematological malignancies. Knowledge of the long-term epidemiology
      of these infections is limited. We surveyed all S. epidermidis blood culture
      isolates from patients treated for hematological malignancies at the University
      Hospital of Orebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis
      isolates were identified and multilocus sequence typing, staphylococcal
      chromosome cassette mec (SCCmec) typing and standard antibiotic susceptibility
      testing were employed to characterize these isolates. The majority of the
      isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were
      divided into 45 sequence types (STs); Simpson's Diversity Index was 0.56. The
      most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). Ninety three
      percent (226/243) of the ST2 isolates displayed either SCCmec type III or IV. ST2
      and 215 were isolated during the entire study period, and together these STs
      caused temporal peaks in the number of positive blood cultures of S. epidermidis.
      Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two
      predominating STs, ST2 and ST215, methicillin resistance was detected in 256/271
      isolates (95%), compared with 34/100 (34%) in other STs (p<0.001). In conclusion,
      in this long-term study of patients with hematological malignancies, we
      demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis
      blood culture isolates. 

PMID- 24896827
TI  - External validation of the MRI-DRAGON score: early prediction of stroke outcome
      after intravenous thrombolysis.
AB  - BACKGROUND AND PURPOSE: The aim of our study was to validate in an independent
      cohort the MRI-DRAGON score, an adaptation of the (CT-) DRAGON score to predict 3
      month outcome in acute ischemic stroke patients undergoing MRI before intravenous
      thrombolysis (IV-tPA). METHODS: We reviewed consecutive (2009-2013) anterior
      circulation stroke patients treated within 4.5 hours by IV-tPA in the Lille
      stroke unit (France), where MRI is the first-line pretherapeutic work-up. We
      assessed the discrimination and calibration of the MRI-DRAGON score to predict
      poor 3-month outcome, defined as modified Rankin Score >2, using c-statistic and
      the Hosmer-Lemeshow test, respectively. RESULTS: We included 230 patients (mean
      +/-SD age 70.4+/-16.0 years, median [IQR] baseline NIHSS 8 [5]-[14]; poor outcome
      in 78(34%) patients). The c-statistic was 0.81 (95%CI 0.75-0.87), and the Hosmer
      Lemeshow test was not significant (p = 0.54). CONCLUSIONS: The MRI-DRAGON score
      showed good prognostic performance in the external validation cohort. It could
      therefore be used to inform the patient's relatives about long-term prognosis and
      help to identify poor responders to IV-tPA alone, who may be candidates for
      additional therapeutic strategies, if they are otherwise eligible for such
      procedures based on the institutional criteria.

PMID- 24896829
TI  - Hysteresis responses of evapotranspiration to meteorological factors at a diel
      timescale: patterns and causes.
AB  - Evapotranspiration (ET) is an important component of the water cycle in
      terrestrial ecosystems. Understanding the ways in which ET changes with
      meteorological factors is central to a better understanding of ecological and
      hydrological processes. In this study, we used eddy covariance measurements of ET
      from a typical alpine shrubland meadow ecosystem in China to investigate the
      hysteresis response of ET to environmental variables including air temperature
      (Ta), vapor pressure deficit (VPD) and net radiation (Rn) at a diel timescale.
      Meanwhile, the simulated ET by Priestly-Taylor equation was used to interpret the
      measured ET under well-watered conditions. Pronounced hysteresis was observed in
      both Ta and VPD response curves of ET. At a similar Ta and VPD, ET was always
      significantly depressed in the afternoon compared with the morning. But the
      hysteresis response of ET to Rn was not evident. Similar hysteresis patterns were
      also observed in the Ta/VPD response curves of simulated ET. The magnitudes of
      the measured and simulated hysteresis loops showed similar seasonal variation,
      with relatively smaller values occurring from May to September, which agreed well
      with the lifetime of plants and the period of rainy season at this site. About
      62% and 23% of changes in the strength of measured ET-Ta and ET-VPD loops could
      be explained by the changes in the strength of simulated loops, respectively.
      Thus, the time lag between Rn and Ta/VPD is the most important factor generating
      and modulating the ET-Ta/VPD hysteresis, but plants and water status also
      contribute to the hysteresis response of ET. Our research confirmed the different
      hysteresis in the responses of ET to meteorological factors and proved the vital
      role of Rn in driving the diel course of ET. 

PMID- 24896828
TI  - An amphisbaenian skull from the European miocene and the evolution of
      Mediterranean worm lizards.
AB  - The evolution of blanid amphisbaenians (Mediterranean worm lizards) is mainly
      inferred based on molecular studies, despite their fossils are common in Cenozoic
      European localities. This is because the fossil record exclusively consists in
      isolated elements of limited taxonomic value. We describe the only known fossil
      amphisbaenian skull from Europe - attributed to Blanus mendezi sp. nov.
      (Amphisbaenia, Blanidae) - which represents the most informative fossil blanid
      material ever described. This specimen, from the Middle Miocene of Abocador de
      Can Mata (11.6 Ma, MN7+8) in the Valles-Penedes Basin (Catalonia, NE Iberian
      Peninsula), unambiguously asserts the presence of Blanus in the Miocene of
      Europe. This reinforces the referral to this genus of the previously-known, much
      more incomplete and poorly-diagnostic material from other localities of the
      European Neogene. Our analysis - integrating the available molecular,
      paleontological and biogeographic data - suggests that the new species postdates
      the divergence between the two main (Eastern and Western Mediterranean) extant
      clades of blanids, and probably precedes the split between the Iberian and North
      Western African subclades. This supports previous paleobiogeographic scenarios
      for blanid evolution and provides a significant minimum divergence time for
      calibrating molecular analyses of blanid phylogeny. 

PMID- 24896830
TI  - An update on HIV.

PMID- 24896831
TI  - Pregnancy's stronghold on the vaginal microbiome.
AB  - OBJECTIVE: To assess the vaginal microbiome throughout full-term uncomplicated
      pregnancy. METHODS: Vaginal swabs were obtained from twelve pregnant women at 8
      week intervals throughout their uncomplicated pregnancies. Patients with symptoms
      of vaginal infection or with recent antibiotic use were excluded. Swabs were
      obtained from the posterior fornix and cervix at 8-12, 17-21, 27-31, and 36-38
      weeks of gestation. The microbial community was profiled using hypervariable tag
      sequencing of the V3-V5 region of the 16S rRNA gene, producing approximately 8
      million reads on the Illumina MiSeq. RESULTS: Samples were dominated by a single
      genus, Lactobacillus, and exhibited low species diversity. For a majority of the
      patients (n = 8), the vaginal microbiome was dominated by Lactobacillus crispatus
      throughout pregnancy. Two patients showed Lactobacillus iners dominance during
      the course of pregnancy, and two showed a shift between the first and second
      trimester from L. crispatus to L. iners dominance. In all of the samples only
      these two species were identified, and were found at an abundance of higher than
      1% in this study. Comparative analyses also showed that the vaginal microbiome
      during pregnancy is characterized by a marked dominance of Lactobacillus species
      in both Caucasian and African-American subjects. In addition, our Caucasian
      subject population clustered by trimester and progressed towards a common
      attractor while African-American women clustered by subject instead and did not
      progress towards a common attractor. CONCLUSION: Our analyses indicate normal
      pregnancy is characterized by a microbiome that has low diversity and high
      stability. While Lactobacillus species strongly dominate the vaginal environment
      during pregnancy across the two studied ethnicities, observed differences between
      the longitudinal dynamics of the analyzed populations may contribute to divergent
      risk for pregnancy complications. This helps establish a baseline for
      investigating the role of the microbiome in complications of pregnancy such as
      preterm labor and preterm delivery.

PMID- 24896832
TI  - Persistence of IgE-associated allergy and allergen-specific IgE despite CD4+ T
      cell loss in AIDS.
AB  - The infection of CD4+ cells by HIV leads to the progressive destruction of CD4+ T
      lymphocytes and, after a severe reduction of CD4+ cells, to AIDS. The aim of the
      study was to investigate whether HIV-infected patients with CD4 cell counts <200
      cells/ul can suffer from symptoms of IgE-mediated allergy, produce allergen
      specific IgE antibody responses and show boosts of allergen-specific IgE
      production. HIV-infected patients with CD4 counts <= 200 cells/ul suffering from
      AIDS and from IgE-mediated allergy were studied. Allergy was diagnosed according
      to case history, physical examination, skin prick testing (SPT), and serological
      analyses including allergen microarrays. HIV infection was confirmed
      serologically and the disease was staged clinically. The predominant allergic
      symptoms in the studied patients were acute allergic rhinitis (73%) followed by
      asthma (27%) due to IgE-mediated mast cell activation whereas no late phase
      allergic symptoms such as atopic dermatitis, a mainly T cell-mediated skin
      manifestation, were found in patients suffering from AIDS. According to IgE
      serology allergies to house dust mites and grass pollen were most common besides
      IgE sensitizations to various food allergens. Interestingly, pollen allergen
      specific IgE antibody levels in the patients with AIDS and in additional ten IgE
      sensitized patients with HIV infections and low CD4 counts appeared to be boosted
      by seasonal allergen exposure and were not associated with CD4 counts. Our
      results indicate that secondary allergen-specific IgE production and IgE-mediated
      allergic inflammation do not require a fully functional CD4+ T lymphocyte
      repertoire.

PMID- 24896834
TI  - Does experience matter? Trainee experience and outcomes during transdiagnostic
      cognitive-behavioral group therapy for anxiety.
AB  - Research examining the impact of therapist experience on client outcomes has
      yielded mixed findings. The current study aimed to improve upon previous research
      by examining the impact of global trainee therapists' experience, as well as
      treatment protocol-specific experience, on client outcomes. Data were obtained
      based on 319 clients being treated by 33 therapists using a 12-week
      transdiagnostic cognitive-behavioral group therapy specifically for anxiety
      disorders. Results demonstrated that clients overall showed significant
      improvement in self-reported anxiety and clinician severity ratings, and that the
      amount of therapist experience was unrelated to improvement. The current study
      suggests that trainee therapists' experience, whether examined as global amount
      of therapy experience or specific experience delivering a specific treatment
      protocol, was unrelated to treatment outcomes or treatment discontinuation across
      a range of outcomes.

PMID- 24896833
TI  - Multi-compartment T2 relaxometry using a spatially constrained multi-Gaussian
      model.
AB  - The brain's myelin content can be mapped by T2-relaxometry, which resolves
      multiple differentially relaxing T2 pools from multi-echo MRI. Unfortunately, the
      conventional fitting procedure is a hard and numerically ill-posed problem.
      Consequently, the T2 distributions and myelin maps become very sensitive to noise
      and are frequently difficult to interpret diagnostically. Although regularization
      can improve stability, it is generally not adequate, particularly at relatively
      low signal to noise ratio (SNR) of around 100-200. The purpose of this study was
      to obtain a fitting algorithm which is able to overcome these difficulties and
      generate usable myelin maps from noisy acquisitions in a realistic scan time. To
      this end, we restrict the T2 distribution to only 3 distinct resolvable tissue
      compartments, modeled as Gaussians: myelin water, intra/extra-cellular water and
      a slow relaxing cerebrospinal fluid compartment. We also impose spatial
      smoothness expectation that volume fractions and T2 relaxation times of tissue
      compartments change smoothly within coherent brain regions. The method greatly
      improves robustness to noise, reduces spatial variations, improves definition of
      white matter fibers, and enhances detection of demyelinating lesions. Due to
      efficient design, the additional spatial aspect does not cause an increase in
      processing time. The proposed method was applied to fast spiral acquisitions on
      which conventional fitting gives uninterpretable results. While these fast
      acquisitions suffer from noise and inhomogeneity artifacts, our preliminary
      results indicate the potential of spatially constrained 3-pool T2 relaxometry. 

PMID- 24896835
TI  - Development of the psychometric property of a Minimum Data-Set-Based Depression
      Rating Scale for use in long-term care facilities in Taiwan.
AB  - OBJECTIVES: Our aim is to develop the psychometric property of the Minimum Data
      Set-Based Depression Rating Scale (MDS-DRS) to ensure its use to assess service
      needs and guide care plans for institutionalized residents. METHODS: 378
      residents were recruited from the Haoran Senior Citizen Home in northern Taiwan.
      The MDS-DRS and GDS-SF were used to identify observable features of depression
      symptoms in the elderly residents. RESULTS: A total of 378 residents participated
      in this study. The receiver operating characteristic (ROC) curve indicated that
      the MDS-DRS has a 43.3% sensitivity and a 90.6% specificity when screening for
      depression symptoms. The total variance, explained by the two factors 'sadness'
      and 'distress,' was 58.1% based on the factor analysis. CONCLUSIONS: Reliable
      assessment tools for nurses are important because they allow the early detection
      of depression symptoms. The MDS-DRS items perform as well as the GDS-SF items in
      detecting depression symptoms. Furthermore, the MDS-DRS has the advantage of
      providing information to staff about care process implementation, which can
      facilitate the identification of areas that need improvement. Further research is
      needed to validate the use of the MDS-DRS in long-term care facilities.

PMID- 24896836
TI  - FcgammaRIIa and FcgammaRIIIb polymorphisms and associations with clinical
      manifestations in systemic lupus erythematosus patients.
AB  - In this study, we aimed to investigate whether the distribution of the
      FcgammaRIIa and FcgammaRIIIb polymorphisms determines susceptibility to systemic
      lupus erythematosus (SLE) and acts as predictors of SLE clinical manifestations
      in the Brazilian patients. A total of 157 patients that fulfilled the American
      College of Rheumatology classification criteria for SLE and 160 healthy
      volunteers were included in this study. FCGR2A and FCGR3B genotypes were
      determined by polymerase chain reaction-based allotyping methods with allele
      specific primers; the clinical features were obtained from the patients' official
      medical records. In the case of FcgammaRIIa polymorphism, it was observed
      association of the allele FCGR2A-R-131 (p = 0.02, odds ratio (OR)=1.44) and
      genotype RR-131 (p = 0.03, OR = 2.09) with SLE. These associations were higher
      with allele (p < 0.01, OR = 1.67) as well genotype (p = 0.01, OR = 2.85) when
      lupus nephritis was considered. In contrast, the allele FCGR2A-H-131 was
      associated with susceptibility to arthritis and anti-DNA antibodies (p = 0.05 for
      both). As for FcgammaRIIIb polymorphism, skewing did not differ significantly
      between patients and controls, however the genotype FCGR3B*02*02 was associated
      with susceptibility to arthritis (p = 0.02) and malar rash (p = 0.03), but no
      association with nephritis was found. The results demonstrate that FcgammaRIIa
      polymorphism is associated with susceptibility to SLE in Brazilian patients,
      whereas for FcgammaRIIIb polymorphism no association was found. However, notably,
      both polymorphisms present allelic variants that influence the clinical
      manifestations and may contribute to the pathogenesis of the disease. In
      addition, to our knowledge, this is the first study considering the frequency of
      FcgammaRIIIb polymorphism in Brazilian SLE patients.

PMID- 24896837
TI  - Oxidizing capacity of periodate activated with iron-based bimetallic
      nanoparticles.
AB  - Nanosized zerovalent iron (nFe0) loaded with a secondary metal such as Ni or Cu
      on its surface was demonstrated to effectively activate periodate (IO4-) and
      degrade selected organic compounds at neutral pH. The degradation was accompanied
      by a stoichiometric conversion of IO4- to iodate (IO3-). nFe0 without bimetallic
      loading led to similar IO4- reduction but no organic degradation, suggesting the
      production of reactive iodine intermediate only when IO4- is activated by
      bimetallic nFe0 (e.g., nFe0-Ni and nFe0-Cu). The organic degradation kinetics in
      the nFe0-Ni(or Cu)/IO4- system was substrate dependent: 4-chlorophenol, phenol,
      and bisphenol A were effectively degraded, whereas little or no degradation was
      observed with benzoic acid, carbamazepine, and 2,4,6-trichlorophenol. The
      substrate specificity, further confirmed by little kinetic inhibition with
      background organic matter, implies the selective nature of oxidant in the nFe0
      Ni(or Cu)/IO4- system. The comparison with the photoactivated IO4- system, in
      which iodyl radical (IO3*) is a predominant oxidant in the presence of methanol,
      suggests IO3* also as primary oxidant in the nFe0-Ni(or Cu)/IO4- system.

PMID- 24896838
TI  - Comparison of single-arm vs. randomized phase II clinical trials: a Bayesian
      approach.
AB  - Single-arm studies are typically used in phase II of clinical trials, whose main
      objective is to determine whether a new treatment warrants further testing in a
      randomized phase III trial. The introduction of randomization in phase II, to
      avoid the limits of studies based on historical controls, is a critical issue
      widely debated in the recent literature. We use a Bayesian approach to compare
      single-arm and randomized studies, based on a binary response variable, in terms
      of their abilities of reaching the correct decision about the new treatment, both
      when it performs better than the standard one and when it is less effective. We
      evaluate how the historical control rate, the total sample size, and the
      elicitation of the prior distributions affect the decision about which study
      performs better. 

PMID- 24896839
TI  - Streptococcus intermedius as causative agent of perianal abscess and metastatic
      brain abscess.

PMID- 24896840
TI  - Separation of double-walled carbon nanotubes by size exclusion column
      chromatography.
AB  - In this report we demonstrate the separation of raw carbon nanotube material into
      fractions of double-walled (DWCNTs) and single-walled carbon nanotubes (SWCNTs).
      Our method utilizes size exclusion chromatography with Sephacryl gel S-200 and
      yielded two distinct fractions of single- and double-walled nanotubes with
      average diameters of 0.93 +/- 0.03 and 1.64 +/- 0.15 nm, respectively. The
      presented technique is easily scalable and offers an alternative to traditional
      density gradient ultracentrifugation methods. CNT fractions were characterized by
      atomic force microscopy and Raman and absorption spectroscopy as well as
      transmission electron microscopy. 

PMID- 24896841
TI  - Complication and mortality rate after percutaneous endoscopic gastrostomy are low
      and indication-dependent.
AB  - OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is often used for the
      feeding of patients with malnutrition due to dysphagia, and despite more than 30
      years experience, numerous questions on its benefit remain. This was a
      prospective observational study to assess the safety of PEG. MATERIAL AND
      METHODS: One hundred and nineteen patients mean age 63 years (21-91 years) who
      were admitted to the Hannover Medical School between November 2010 and March 2012
      and had an indication for PEG according to the German guidelines were included.
      Primary endpoints were the following: reason for indication, date of in-hospital
      mortality after PEG insertion, death within 3 months after PEG placement, and
      complications. RESULTS: Most patients (54.6%) received PEG for dysphagia caused
      by tumors and second (29.4%) for neurologic diseases with a minor proportion of
      dementia (3%). About 73% of our patients had no complications at all and only 10%
      suffered severe effects. We saw only 1 case of aspiration, which did not lead to
      pneumonia. The 30-day mortality was 10%, and no patient died as a result of the
      PEG procedure. Significantly more patients with neurologic disorders died within
      24 weeks of PEG placement than tumor patients (60% versus 27.7%, respectively, p
      = 0.002, n = 100). CONCLUSION: It is important to select patients receiving PEG
      very carefully. The patients' indications, their primary disease, and their
      capability for mental cooperation are essential. If these aspects are taken into
      account, PEG is a safe method with few mainly mild complications.

PMID- 24896842
TI  - New investigational drugs for the treatment of neuropathic pain.
AB  - INTRODUCTION: Neuropathic pain (NP) is a chronic condition that arises from a
      lesion or dysfunction of the somatosensory nervous system. However, there are
      several new targets and novel technologies in the pipeline to address this unmet
      medical need. AREAS COVERED: In this review, the authors briefly discuss a
      direction of the development of agents that could be potentially used in NP
      treatment. Special attention is paid to 1.7-selective voltage-gated sodium
      channels, N-type voltage-gated calcium channels, angiotensin II (Ang II) AT2
      receptors and nerve growth factor (NGF) as promising targets for new drugs.
      Furthermore, the article also presents and discusses, in detail, the results of
      Phase II clinical studies with the AT2 receptor antagonist - EMA401 in NP (the
      results of Phase II clinical trials of other described compounds are not
      available, yet). EXPERT OPINION: There is a real hope that new drugs for NP may
      be available soon. This hope is based on advancing methods of genomics,
      developing new targets and more efficient drug screening. Some forms of direct
      influence on voltage-gated ion channels have a place in the treatment of NP,
      while the development of entirely novel Ang II AT2 receptor antagonists or NGF
      inhibitors may be available for many chronic pain sufferers in the foreseeable
      future.

PMID- 24896843
TI  - Rational construction of triazole/urea based peptidomimetic macrocycles as
      pseudocyclo-beta-peptides and studies on their chirality controlled self
      assembly.
AB  - A tandem macro-dimerization reaction via a Cu(I) catalyzed azide/alkyne
      cycloaddition reaction has been employed to construct triazole/urea based
      peptidomimetic macrocycles considered as pseudocyclo-beta-peptides. Introduction
      of one particular chirality in the peptide backbone can alter the conformation as
      well as nature of self-assembly from cyclic D-,L-,alpha-peptide to cyclo-beta
      peptide. One of them (16a) forms antiparallel dimers while the other (16b)
      undergoes higher order aggregation to form a nanorod structure.

PMID- 24896844
TI  - High-accuracy theoretical thermochemistry of fluoroethanes.
AB  - A highly accurate coupled-cluster-based ab initio model chemistry has been
      applied to calculate the thermodynamic functions including enthalpies of
      formation and standard entropies for fluorinated ethane derivatives, C2HxF6-x (x
      = 0-5), as well as ethane, C2H6. The invoked composite protocol includes
      contributions up to quadruple excitations in coupled-cluster (CC) theory as well
      as corrections beyond the nonrelativistic and Born-Oppenheimer approximations.
      For species CH2F-CH2F, CH2F-CHF2, and CHF2-CHF2, where anti/gauche isomerism
      occurs due to the hindered rotation around the C-C bond, conformationally
      averaged enthalpies and entropies at 298.15 K are also calculated. The results
      obtained here are in reasonable agreement with previous experimental and
      theoretical findings, and for all fluorinated ethanes except CH2FCH3 and C2F6
      this study delivers the best available theoretical enthalpy and entropy
      estimates. 

PMID- 24896850
TI  - Catalytic formation of ammonia from molecular dinitrogen by use of dinitrogen
      bridged dimolybdenum-dinitrogen complexes bearing PNP-pincer ligands: remarkable
      effect of substituent at PNP-pincer ligand.
AB  - A series of dinitrogen-bridged dimolybdenum-dinitrogen complexes bearing 4
      substituted PNP-pincer ligands are synthesized by the reduction of the
      corresponding molybdenum trichloride complexes under 1 atm of molecular
      dinitrogen. In accordance with a theoretical study, the catalytic activity is
      enhanced by the introduction of an electron-donating group to the pyridine ring
      of PNP-pincer ligand, and the complex bearing 4-methoxy-substituted PNP-pincer
      ligands is found to work as the most effective catalyst, where 52 equiv of
      ammonia are produced based on the catalyst (26 equiv of ammonia based on each
      molybdenum atom of the catalyst), together with molecular dihydrogen as a side
      product. Time profiles for the catalytic reactions indicate that the rates of the
      formation of ammonia and molecular dihydrogen depend on the nature of the
      substituent on the PNP-pincer ligand of the complexes. The formation of ammonia
      and molecular dihydrogen is complementary in the reaction system. 

PMID- 24896845
TI  - Intravesical ALT-803 and BCG treatment reduces tumor burden in a carcinogen
      induced bladder cancer rat model; a role for cytokine production and NK cell
      expansion.
AB  - Intravesical Bacillus Calmette-Guerin (BCG) has been shown to induce a specific
      immunologic response (i.e., activation of IL-2 and effector T-cells), while
      preclinical studies using ALT-803 (mutated IL-15 analogue combined with IL
      15Ralpha-Fc fusion) have shown promising results by prolonging the agent's half
      life and stimulating CD8+ T-cells. Based on these results, we hypothesized that
      the intravesical administration of ALT-803 along with BCG will generate an
      immunologic response leading to significant bladder tumor burden reduction. Using
      a well-established carcinogen induced rat non-muscle invasive bladder cancer
      (NMIBC) model, we studied the effects of intravesical ALT-803 with and without
      BCG. Rat tissues were evaluated to document treatment response. Intravesical ALT
      803 was safe and well tolerated alone and in combination with BCG. As a single
      treatment agent, ALT-803 reduced tumor burden by 35% compared to control whereas
      BCG alone only reduced tumor burden by 15%. However, the combination of ALT-803
      plus BCG reduced tumor burden by 46% compared to control. Immune monitoring
      suggested that the antitumor response was linked to the production and secretion
      of IL-1alpha, IL-1beta and RANTES, which in turn, induced the proliferation and
      activation of NK cells. Lastly, tumoral responses of the combinational treatment
      were associated with 76% reduction in angiogenesis, which is significantly higher
      than when assessed with either agent alone. The enhanced therapeutic index seen
      with this duplet provides justification for the development of this regimen for
      future clinical trials.

PMID- 24896848
TI  - Six-month incidence and persistence of oral HPV infection in HIV-negative and HIV
      infected men who have sex with men.
AB  - OBJECTIVES: Our aim was to assess incidence and persistence of oral HPV infection
      in HIV-negative and HIV-infected men who have sex with men (MSM). METHODS: MSM
      aged >=18 years were included in Amsterdam (the Netherlands) in 2010-2011, and
      followed up 6 months later. Participants completed risk factor questionnaires.
      HPV DNA was analyzed in oral-rinse and gargle specimens using the SPF10-PCR
      DEIA/LiPA25 system (version 1). A subset of oral samples was subjected to SPF10
      sequencing to identify additional HPV types. Multivariable logistic regression
      analyses using generalized estimating equations (GEE) were performed to assess
      determinants for oral high-risk HPV incidence and persistence. RESULTS: 689/795
      participant MSM provided both baseline and 6-month data. Baseline prevalence of
      high-risk HPV was 9.4% in HIV-negative and 23.9% in HIV-infected MSM (P<0.001).
      56/689 MSM acquired >=1 high-risk HPV infection (6-month incidence 8.1%; 95%CI
      6.2-10.4%); incidence was 4.1% in HIV-negative and 14.1% in HIV-infected MSM
      (P<0.001). HIV infection and recent use of cannabis were both independently
      associated with high-risk HPV incidence. Persistent high-risk HPV was observed in
      48/130 (36.9%) infections. CONCLUSION: Incidence of oral high-risk HPV infection
      in MSM is substantial, and is associated with HIV infection. Over a third of HPV
      infections persisted over a 6-month period.

PMID- 24896847
TI  - The multicopper ferroxidase hephaestin enhances intestinal iron absorption in
      mice.
AB  - Hephaestin is a vertebrate multicopper ferroxidase important for the transfer of
      dietary iron from intestinal cells to the blood. Hephaestin is mutated in the sex
      linked anemia mouse, resulting in iron deficiency. However, sex-linked anemia
      mice still retain some hephaestin ferroxidase activity. They survive, breed, and
      their anemia improves with age. To gain a better understanding of the role of
      hephaestin in iron homeostasis, we used the Cre-lox system to generate knockout
      mouse models with whole body or intestine-specific (Villin promoter) ablation of
      hephaestin. Both types of mice were viable, indicating that hephaestin is not
      essential and that other mechanisms, multicopper ferroxidase-dependent or not,
      must compensate for hephaestin deficiency. The knockout strains, however, both
      developed a microcytic, hypochromic anemia, suggesting severe iron deficiency and
      confirming that hephaestin plays an important role in body iron acquisition.
      Consistent with this, the knockout mice accumulated iron in duodenal enterocytes
      and had reduced intestinal iron absorption. In addition, the similarities of the
      phenotypes of the whole body and intestine-specific hephaestin knockout mice
      clarify the important role of hephaestin specifically in intestinal enterocytes
      in maintaining whole body iron homeostasis. These mouse models will serve as
      valuable tools to study the role of hephaestin and associated proteins in iron
      transport in the small intestine and other tissues. 

PMID- 24896851
TI  - Interactions of casein micelles with calcium phosphate particles.
AB  - Insoluble calcium phosphate particles, such as hydroxyapatite (HA), are often
      used in calcium-fortified milks as they are considered to be chemically
      unreactive. However, this study showed that there was an interaction between the
      casein micelles in milk and HA particles. The caseins in milk were shown to bind
      to the HA particles, with the relative proportions of bound beta-casein, alphaS
      casein, and kappa-casein different from the proportions of the individual caseins
      present in milk. Transmission electron microscopy showed no evidence of intact
      casein micelles on the surface of the HA particles, which suggested that the
      casein micelles dissociated either before or during binding. The HA particles
      behaved as ion chelators, with the ability to bind the ions contained in the milk
      serum phase. Consequently, the depletion of the serum minerals disrupted the milk
      mineral equilibrium, resulting in dissociation of the casein micelles in milk. 

PMID- 24896853
TI  - The global alliance for genomics & health.

PMID- 24896854
TI  - Intrinsic exploration in animals: motives and measurement.
AB  - Intrinsic exploration involves exploratory acts that are not instrumental in
      achieving any particular goal other than performance of the acts themselves. Of
      the theories proposed to account for the motivation of intrinsic exploration in
      animals, concepts of exploratory drive, optimal arousal and fear have featured
      prominently. But since no single approach has adequate explanatory or predictive
      power, it is probably sufficient to go no further than accept that organisms may
      have some type of 'need' for sensory change which can be satisfied mainly by
      intrinsic exploration. Attempts to measure the phenomenon in the laboratory can
      be divided into forced tests in which locomotion and other motor responses are
      recorded in animals placed into a totally novel environments, and free tests
      involving measurements of active choices of differing degrees of novelty. Because
      of the difficulty of distinguishing between extrinsic and intrinsic exploration
      with activity indices, tests of free exploration are always preferable. These
      include novelty-related location preferences (including spontaneous alternation
      and responses to brightness change), object exploration and learning for
      exploratory rewards all of which can be viewed as reasonably valid measures of
      intrinsic exploration to a greater or lesser extent. 

PMID- 24896855
TI  - Win-stay/lose-shift and win-shift/lose-stay learning by pigeons in the absence of
      overt response mediation.
AB  - Win-stay/lose-shift and win-shift/lose-stay behavior in pigeons was compared
      using a two-alternative conditional discrimination for which the number of trials
      involving each of the task components could be precisely controlled. One group
      was rewarded for pecking the location just pecked if those pecks were followed by
      food and for pecking the other location if those pecks were not followed by food
      (win-stay/lose-shift). Another group was rewarded for pecking the location just
      pecked if those pecks were not followed by food and for pecking the other
      location if those pecks were followed by food (win-shift/lose-stay). With
      increasing delay to comparison choice, pigeons were more accurate on trials when
      initial pecking was followed by the absence of food than by food (Experiment 1).
      However, when hypothesized overt response mediation was discouraged (Experiment
      2), a win-stay superiority effect emerged with increasing delay to comparison
      choice. Thus, unlike rats, pigeons may be somewhat predisposed to repeat a
      response to a location to which responses have been previously rewarded. 

PMID- 24896852
TI  - Early endosomal escape of a cyclic cell-penetrating peptide allows effective
      cytosolic cargo delivery.
AB  - Cyclic heptapeptide cyclo(FPhiRRRRQ) (cFPhiR4, where Phi is l-2-naphthylalanine)
      was recently found to be efficiently internalized by mammalian cells. In this
      study, its mechanism of internalization was investigated by perturbing various
      endocytic events through the introduction of pharmacologic agents and genetic
      mutations. The results show that cFPhiR4 binds directly to membrane
      phospholipids, is internalized into human cancer cells through endocytosis, and
      escapes from early endosomes into the cytoplasm. Its cargo capacity was examined
      with a wide variety of molecules, including small-molecule dyes, linear and
      cyclic peptides of various charged states, and proteins. Depending on the nature
      of the cargos, they may be delivered by endocyclic (insertion of cargo into the
      cFPhiR4 ring), exocyclic (attachment of cargo to the Gln side chain), or bicyclic
      approaches (fusion of cFPhiR4 and cyclic cargo rings). The overall delivery
      efficiency (i.e., delivery of cargo into the cytoplasm and nucleus) of cFPhiR4
      was 4-12-fold higher than those of nonaarginine, HIV Tat-derived peptide, or
      penetratin. The higher delivery efficiency, coupled with superior serum
      stability, minimal toxicity, and synthetic accessibility, renders cFPhiR4 a
      useful transporter for intracellular cargo delivery and a suitable system for
      investigating the mechanism of endosomal escape. 

PMID- 24896856
TI  - Seasonal changes of hippocampus volume in parasitic cowbirds.
AB  - Avian brain plasticity has been demonstrated by seasonal variations in
      neuroanatomy correlated with changes in singing and hoarding behaviour. We report
      a new instance of plasticity. Brood parasitism in South American cowbirds
      involves memory for location of hosts' nests, and is associated with an enlarged
      hippocampus relative to telencephalon size. This effect holds between sexes and
      species during the breeding season. We report that for two parasitic species,
      relative hippocampal volume is smaller during the non-breeding than the breeding
      season, and that sexual dimorphism present in summer in one of the species is not
      found in winter. These results support the hypothesis that the avian hippocampal
      formation shows neuroanatomical plasticity associated with seasonal changes in
      spatial memory demands. 

PMID- 24896857
TI  - Interplay of directional navigation mechanisms as a function of near-goal
      distance: experiments with the house mouse.
AB  - Mice (Mus musculus) that shuttle between their nest and an outside goal use
      different navigation mechanisms, depending on their distance from the nest. This
      was studied by rotating directional cues and the mice relative to one another.
      Close to home (20-50 cm) mice choose path integration and orientation by beacon,
      while farther away from the nest distal landmark orientation becomes more
      important. The larger the beacon is at the home site, the greater is the distance
      over which it is used as a directional cue. As mice head towards their nest, they
      demonstrate a tendency to home by means of distal landmarks at large distances,
      and by means of path integration or guided beacon integration at smaller
      distances. This space related sequence in the use of orientation mechanisms is
      the reverse from the temporal sequence (stages) of learning mechanisms employed
      when first learning to navigate home (Alyan and Jander, 1994). 

PMID- 24896858
TI  - Stability over situations in temperamental traits of horses as revealed by
      experimental and scoring approaches.
AB  - Individual behavioural reactions of adult horses in a variety of experimental
      tests were compared with ratings by riding teachers. The tests were made in a non
      working situation, with the animals being released in an arena, a box (arena
      test, new object test, learning tests) or handled (new object/handling
      situation). The traits rated by teachers were fearfulness, nervousness,
      gregariousness and learning abilities at work (ridden or handled). Despite a
      great homogeneity in the reactions exhibited by the horses in the different
      situations, large individual differences were present. Correlations appeared
      between the reactivity in the arena test and the score of gregariousness, between
      the reactivity in the novel object test and the rating of nervousness when
      ridden, between the results in the handling test and the rating of general
      fearfulness and between the ability to memorise an instrumental task and the
      score of general learning ability. Such results strengthen the idea that there
      are underlying behavioural dispositions that are stable across situations and
      that the experimental tests may be good predictors of the temperament in
      untrained animals. 

PMID- 24896859
TI  - On the generality of choice ordering in object retrieval by Norway rats.
AB  - These studies examined choices made in the course of object retrieval when more
      than one kind of object was available. During a retrieval session, or 'trial', a
      rat could (repeatedly) retrieve either of two types of object drawn from a set of
      three, when each type of object was located in one arm of a Y-maze connected to
      the home cage. In Experiment 1 objects varied in degree of partibility, i.e.
      their capacity to be taken apart by gnawing. Experiment 2 included sweet and
      partible objects. In both studies, after a series of trials, each rat developed a
      stable preference hierarchy, in terms of relative numbers of objects retrieved,
      that depended on choices distributed through most of the retrieval sequence. As
      in studies with sweet objects, responsiveness to the middle object in a hierarchy
      was higher when it was paired with the less- than with the more-preferred object.
      After preferences stabilized, each trial began with a period of sampling,
      followed by rapid shifts in responsiveness in favor of the preferred object. This
      work shows that the capacity to order choices and retrieval preferences holds for
      different object features and across motivational boundaries. 

PMID- 24896860
TI  - Defensive burying in two strains of rats selected for emotional reactivity.
AB  - This paper examined defensive burying in Tsukuba High- and Low-Emotional rats
      (THE and TLE). The THE rats showed significantly more defensive burying and more
      immobility than the TLE rats. The TLE rats were more active and started prod
      investigation faster than the THE rats. Some TLE rats bit the prod immediately
      after shock administration. No significant strain differences were observed in
      passive avoidance (stay away from the prod) and time spent at prod-investigation.
      The results indicate that THE rats are active and TLE rats are inactive in
      relation to defensive burying, although THE rats generally show passive coping.
      The relation between defensive burying and strain-specific coping styles is
      discussed. 

PMID- 24896861
TI  - A method for identifying the nearby spatial cues used by animals during
      transverse orientation.
AB  - A method was proposed to locate the nearby cues used by an animal in the case of
      transverse orientation, where the animal keeps a constant angle with a spatial
      cue. By studying the value constancy of the angles formed by a moving animal and
      the direction of all spatial points (constancy being expressed through more or
      less strong variances), we set up a cartography of the neighbouring space of this
      animal during a path. Relatively to the area where a low variance is found for
      angular values, the animal maintains the best angular constancy. The orientating
      cue used during this path is probably included in this area. The method
      efficiency is first tested on path models, and then applied to filmed walking
      crickets. Its heuristic value is established whenever the observer do not want a
      priori assess the cues the animal is supposed to choose. The practical interest
      of the method lies in the knowledge it provides of the relative role played by
      the body axis translations and rotations in the visual fixation and retinal
      scanning of crickets. 

PMID- 24896862
TI  - [Not Available].
AB  - Since Jensen (1963), the phenomenon of "contrafreeloading" corresponds to the
      fact that animals which have been conditioned to perform a task (by skinnerian
      conditioning for instance) continue to behave as they have been taught to even
      when a more simple and effortless solution is made available to them (for
      instance free access to abundant food in skinnerian situation). This behaviour
      has been considered as an exception to the "law of the least effort" (Tolman,
      1955). To explain it, two types of theories have been put forward. The first one
      assumes the existence of positive reinforcers connected with the acquired
      activity, the other one of aversive stimulus connected with the most effortless
      solution (such as neophobia in the case of cup of abundant food). A
      reconsideration of the analysis of operant behaviour has led us to take into
      account the localisation of reinforcing agents and to integrate it in our
      experiments. The results that have been obtained cannot be accounted for by the
      theories mentioned above. 

PMID- 24896863
TI  - Momentary and global maximizing.
AB  - Four adult females responded at a computer console, on three constant probability
      concurrent variable-interval reinforcement schedules. The subjects were
      instructed to try to obtain as many reinforcers as possible, but were not given
      any instructions on how to accomplish this task. Three of the four subjects
      typically allocated responses to the schedule offering the higher reinforcement
      probability. These results show that some subjects trying to maximize overall
      reinforcement may respond in accordance with a momentary maximizing strategy. 

PMID- 24896864
TI  - Phylogenesis / biotope interactions among formicidae.
AB  - The development of interspecific recognition and the expression of behavioral
      plasticity as a function of phyletic distance and the natural environment in
      which the ants live were investigated. An experimental model involving artificial
      mixed societies was used in this study. These mixed societies were produced by
      combining ants from two out of the 11 investigated species. The possibilities
      thus ranged from situations in which phylogenetically similar ants that live in
      the same biotype were combined, to those in which the species differ
      significantly in terms both of phyletic distance and of biotope. The
      interspecific groups were established in a neutral environment with adult ants
      less than 24 hours old. The results concerned agonistic and non-agonistic
      behaviors during the first 15 days. Both the frequency and types of interaction
      were shown to vary according to the type of group. Two species that share a
      common habitat are less aggressive and display more non-agonistic behavior than
      when the species come from different habitats. On the other hand, although
      aggressive behaviors increase with greater phyletic distance between the species,
      non-agonistic interactions remain constant. As a general rule, interactions
      between species from differing environments seem to be determined by the phyletic
      distance, whereas those between species from the same biotope are controlled by
      interspecific competition. There is a gradual change in these interactions
      dependent on the duration of the mixed association. 

PMID- 24896865
TI  - Adult chicken alarm calls enhance tonic immobility in chicks.
AB  - An experimenter induced tonic immobility (TI) in parentally naive chicks (G.
      gallusdomesticus). The chicks remained in TI longer when they were exposed to a
      conspecific adult fear squawk alarm call than when exposed to an equally novel
      attraction call or white noise. In a second experiment, both aerial-predator and
      ground-predator alarm calls enhanced TI similarly to the fear squawk call which
      is elicited by capture. These results support the hypotheses that TI is an
      antipredator defense mechanism and that alarm calls evolved through kin
      selection. 

PMID- 24896866
TI  - [Not Available].
AB  - Mating behavior was studied in S. charlottae and S. emiliae cave Bathysciinae.
      Actions of the male vary with the species. S. charlottae rubs the female abdomen
      with his mesothoracic legs whereas his abdomen is motionless; S. emiliae performs
      many antero-posterior abdominal movements, very strong at the beginning, then
      weaker. Concerning the duration of copulations in S. charlottae species, long or
      short matings occur, without a regular rythm. Among Bathysciinae, behavioral data
      permit a taxinomic discrimination and may show the relation-ships between
      species. 

PMID- 24896867
TI  - Analyzing stereotypy in red deer alarm postures by means of informational
      redundancy.
AB  - The variability in duration and form or red deer (Cervus elaphus ) alarm postures
      was studied. 18 variables of form were measured from photographic sequences and
      stereotypy calculated by means of Informational redundancy (IR). Comparisons
      between stereotypy estimates obtained by IR and those provided by the widely used
      coefficient of variation proved to match each other well. Durations showed less
      stereotypy than configurational variables as measured by coefficient of
      variation. Some implications of the results are discussed. Since IR has never
      been applied before to the analysis of formal stereotypy in Modal Action
      Patterns, we studied several features of the method, including the effect of
      sample size and differential number of categories on IR values. Last, we support
      the use of informational measurements in analyzing Modal Action Patterns as they
      correspond satisfactorily whith some conceptual issues in current use. 

PMID- 24896868
TI  - Mechanisms for turn alternation in four invertebrate species.
AB  - Free-choice behavior following one or more forced turns was observed in
      representatives of four invertebrate classes (earthworms, woodlice, millipedes,
      earwigs). While all animals alternated, species differences occurred in free turn
      angle and the effects of varied angle and number of forced turns. Overall,
      woodlice and millipedes turned at sharper angles and responded more to the forced
      turn conditions than earthworms and earwigs. From behavior observed following
      three forced turns in one direction and then one in the opposite, it was
      concluded that, in earlier experiments, earthworms alternated via tactile cues,
      woodlice mainly used kinesthetic but could also use tactile cues, millipedes
      mainly used tactile but could also use kinesthetic cues and earwigs may have
      relied on kinesthetic cues alone. Since phyletic differences did not seem
      appropriate, the results were discussed in terms of other characteristics such as
      body shape and life style. 

PMID- 24896869
TI  - Computer simulation of pigeons' performance on a spatial memory task.
AB  - Delayed matching of key location is a useful paradigm for the study of pigeons'
      short-term memory for a spatial location. On each trial a randomly selected key
      from a matrix of keys is lit briefly as a sample and followed by a retention
      interval. During the ensuing choice period the sample and one of the non-sample
      keys are lit; choice of the sample is correct and rewarded whereas choice of the
      distractor key is not. The computer simulation of performance on this task is
      based on a simple model: We assume that the pigeon has knowledge of the location
      of the keys stored in a map-like reference memory. We also assume that short-term
      memory involves an attention focus or "pointer" that "drifts" on the surface of
      this map. The pointer migrates from a randomly determined position during the
      intertrial interval towards the location of the sample when this stimulus is
      presented. It wanders randomly from its previous position when this cue is no
      longer present in the retention interval. During the test for retention the bird
      selects the location (i.e., sample or distractor) closer to the location of the
      pointer on the map of the matrix. The simulation successfully reproduced several
      of the phenomena observed in delayed matching of location experiments and
      provided an account of some hitherto perplexing results. As well, the model
      successfully predicted some new empirical data. 

PMID- 24896870
TI  - Olfactory cues in host nest detection by the social parasite Polistes sulcifer
      (Hymenoptera, Vespidae).
AB  - Sometimes the nests of the paper wasp Polistes dominulus are parasitized by the
      obligate social parasite Polistes sulcifer. It is not known how, in the spring,
      this parasite searches for established nests of its host species. This study
      investigates the capacity to detect the host nest by olfactory cues alone. In
      laboratory experiments P. sulcifer females were allowed to choose different
      options hidden from view: host nest and dummy, various portions of the host nest
      (larvae, pupae and material), nests or immature brood pertaining to different
      sympatric species (P. dominulus, P. nimpha and P. gallicus). The parasites proved
      to be capable of perceiving nest odour and of discriminating between different
      species of Polistes. The odour of the immature host brood, rather than the nest
      material, elicits the greatest response in the parasites. 

PMID- 24896871
TI  - Selecting dominants and subordinates at conflict outcome can confound the effects
      of prior dominance or subordination experience.
AB  - Individuals with a previous experience of dominance are likely to be dominants in
      further encounters. To test this effect, individuals with a previous experience
      of dominance are used for the experiments. One way to obtain such individuals is
      to let opponents 'self-select': encounters between pairs of more or less
      equivalent opponents are staged and one selects ex post facto the dominant and
      subordinate from the ensuing conflict. This paper formally shows that the
      selection of dominant and subordinate animals modifies the dominance probability
      functions of the two corresponding sub-samples of animals. As a result, the
      propensity of previous winners to win again and of previous losers to repeat
      their loss can be attributed to this artefact rather than to prior social
      experience. This result has serious methodological implications. When one relies
      solely on selection to obtain winners and losers, equiprobability is no longer
      the appropriate null hypothesis against which prior social experience effects
      have to be tested. To clearly demonstrate the effect of dominance experience, one
      must show that prior winners defeat neutral opponents in at least two-thirds of
      all cases; reciprocally, to show that prior subordinate experience plays a role,
      prior losers must win in less than one-third of all fights against neutral
      opponents; finally, to conclude that a combined effect of the two kinds of prior
      experience is in operation, one must obtain that prior winners defeat prior
      losers in more than 83% of all planned conflicts. The present result does not
      imply that experience effects are not at work when the selection procedure is
      used, but that the procedure used to show their effects is inadequate because
      effects of experience on a subsequent encounter are confounded with those
      introduced by statistical selection. 

PMID- 24896872
TI  - May random processes explain mating success in leks?
AB  - The object of this paper is to verify whether in specific cases the variance of
      mating success among lekking males may be due exclusively to a random mechanism,
      as opposed to the adaptive mechanisms of mate choice which are usually postulated
      in the literature in the framework of sexual selection theory. In fact, some
      studies attempted to compare observed distributions of male mating success with a
      Poisson 'null' distribution based on the conjecture of random mating; the
      conjecture is usually rejected. In this paper we construct a plausible model (the
      'null' hypothesis) for a strictly random non-adaptive pattern of social behaviour
      of lekking males and females and we perform several simulations for reasonable
      choices of parameter values. It should be observed that some of the simulations
      based on our random model lead to a distribution of male mating success which is
      Poisson-like. However, contrary to predictions, in several simulations a random
      process of mate choice lead to non-Poissonian distributions. Accordingly, the
      fact that, when performing a statistical test on several sets of field data, we
      find both cases which are in agreement with Poisson distribution, or a normal
      one, and cases which are not, does not allow us to reject the assumption of
      random male reproductive success. Thus it is legitimate to conjecture that in
      many cases the inter-individual variability of male mating success might indeed
      be determined by random processes. If this conjecture were to be confirmed by
      further studies, the actual significance of sexual selection in the evolution of
      lekking species should be reassessed, and a novel approach in the analysis of
      field data would be called for. 

PMID- 24896874
TI  - Time-place learning in golden shiners (Pisces: Cyprinidae).
AB  - The goal of this study was to determine whether fish can learn to forage in
      different places at different times of the day, each place being associated with
      a specific time. Groups of eight golden shiners (Notemigonus crysoleucas) were
      kept in aquaria equipped with automatic feeders that dropped food on one side in
      the morning and on the other side in the afternoon, or on one side in the
      morning, the other side at midday, and back on the first side in the evening.
      After 3-4 weeks, food was withheld and the position of the fish within the
      aquaria was noted at 5-min intervals throughout the day. Consistent with time
      place learning, most fish were on the correct side at the correct time. However,
      another experiment with three places instead of two provided only equivocal
      evidence of time-place learning; this could reflect the fact that, in the lakes
      they inhabit, golden shiners may need only distinguish between two places: open
      waters and littoral. Experiments with phase-shifts of the photoperiod showed that
      temporal discrimination is based on a circadian clock that can be gradually phase
      advanced by 6 h in about 3 days. 

PMID- 24896873
TI  - Attenuation and reacquisition of foraging behavior in a patchy environment.
AB  - The present experiment examined the attenuation and reacquisition of foraging
      behavior of pigeons on a restricted diet. Using the procedure of Roberts (1988),
      thirty-two feeders were arranged in four circular patches of eight feeders each.
      The feeders were baited so that each patch contained a different density of food.
      Pigeons learned to forage among the patches. During this initial acquisition
      phase, visits to the patches by the pigeons differed as a function of the food
      density of the patches. After this initial foraging training phase, each pigeon
      received one of two response elimination procedures. For half of the subjects,
      food was not present during the response elimination phase. For the remaining
      subjects, food was placed exclusively outside the patches during this phase.
      Foraging behavior decreased quickly and somewhat similarly for both conditions.
      During a final phase in which the retraining of the original foraging behavior
      occurred, the group given food outside the patches during response elimination
      provided evidence of superior foraging with respect to sensitivity to the
      different patch food densities. The results are discussed with regard to
      previously published response elimination effects. 

PMID- 24896875
TI  - Schedule segmentation and delay-reduction theory.
AB  - In order to explain the data obtained from studies which examined effects of
      schedule segmentation on choice, the present study proposed five quantitative
      models stemming from delay-reduction theory. A total of 108 choice proportions
      reported in the schedule segmentation literature were plotted against choice
      proportions predicted by the models. Linear regression equations and their
      correlation coefficients were then obtained by the method of least squares, in
      order to examine which of the five equations was the best in explaining the
      obtained data. The best model determined the values of the alternatives by
      multiplying the values of conditioned stimuli associated with them, each of which
      was obtained by subtracting a non-reinforcement interval after its offset from an
      amount of delay reduction informed by its onset. 

PMID- 24896876
TI  - The role of trial tracking on rats' successive delayed matching-to-sample
      modality performance.
AB  - The present study tested a trial tracking hypothesis that rats' matching accuracy
      to sample modality (onset of chamber lights or a tone) in a successive delayed
      matching task is, in part, determined by their ability to determine whether they
      are within or between trials during an interstimulus interval. In this
      discrimination rats had to respond to an initial sample stimulus to obtain a
      second test stimulus, S2. Responding to S2 was reinforced only when it matched
      S1. The interstimulus intervals between S1 and S2, the retention interval, and
      between S2 and the next S1, the intertrial interval, were varied. The prediction
      that more accurate trial tracking would be maintained by rats that were only
      reinforced for correctly responding S2 (S1 Nonreinforcement group) than by rats
      that were reinforced for responding to each S1 as well as to its matching S2 (S1
      Reinforcement group) was supported. Increasing retention intervals caused steeper
      declines in matching accuracy in the S1 Reinforcement group. Although matching
      accuracy to the tone S1 was generally but slightly reduced by decreasing
      intertrial intervals from 24 s to 12 s or 6 s, this effect was confined to 1-s
      and 5-s retention intervals only in the S1 Reinforcement group. A similar
      prediction based on differences in the required number of presses to each
      stimulus event was not supported. Also noteworthy were results showing superior
      matching accuracy to the light S1 than to the tone S1. While increasing retention
      intervals to 20 s eliminated this difference in the S1 Nonreinforcement group,
      increasing retention intervals to 5 s or more brought about this effect in the S1
      Reinforcement group. 

PMID- 24896877
TI  - Learning of colour and position cues in domestic chicks: Males are better at
      position, females at colour.
AB  - Male and female chicks were trained to discriminate between two boxes for food
      reinforcement. The correct box was indicated by a colour cue (red or brown) and a
      position cue (right or left). After learning, the colour and the position cues
      were dissociated: the right-left location of the two boxes was alternated between
      trials according to a semi-random sequence.The chicks were thus retrained to
      discriminate either on the basis of colour (irrespective of position) or on the
      basis of position (irrespective of colour). There were no sex differences, during
      training, with both position and colour cues. However, during re-training females
      performed better on the colour learning task and males performed better on the
      position learning task. 

PMID- 24896878
TI  - Head-up behavior induced by low-doses of X-irradiation in the mouse and its
      disappearance by zinc sulfate perfusion in the nasal passage.
AB  - X-rays are commonly said to be one of many stimulus agents which are not
      perceivable by the sensory organs of mammals. However, I observed an interesting
      phenomenon where a mouse lifted its head and looked up (head-up behavior) while
      keeping its body flat on the floor when a mouse was given low-doses whole-body X
      irradiation emitted from above. An attempt was made to examine whether mice could
      discern the direction of an X-ray source. I observed EEG responses and the head
      up behavior when the mice were exposed to 4 cGy X-rays from more than one angle.
      The results showed that the mice awoke immediately and displayed the head-up
      behavior when those showing non-REM sleep were given 4 cGy X-rays emitted from
      above, below or from the side of the mouse. Mice showing REM sleep, however,
      showed no such behavior. Furthermore, the head-up behavior was not observed at
      all, even after 4 cGy X-irradiation, when the mouse was deprived of its olfactory
      sense by ZnSO4 solution. These results show that mice could detect low-doses of X
      rays, without knowing the direction of the source, and peripheral olfactory cells
      were possibly involved in this detection. 

PMID- 24896879
TI  - Interaction and aggregation of charged platelets in electrolyte solutions: a
      coarse-graining approach.
AB  - A coarse-graining approach has been developed to replace the effect of explicit
      ions with an effective pair potential between charged sites in anisotropic
      colloidal particles by optimizing a potential of mean force against the results
      of simulations of two such colloidal particles with all ions in a cell model.
      More specifically, effective pair potentials were obtained for charged platelets
      in electrolyte solutions by simulating two rotating parallel platelets with ions
      at the primitive model level, enclosed in a cylindrical cell. One-component bulk
      simulations of many platelets interacting via the effective pair potentials are
      in excellent agreement with the corresponding bulk simulations with all mobile
      charges present. The bulk simulations were mainly used to study the effects of
      platelet size, flexibility, and surface charge density on platelet aggregation in
      an aqueous 2:1 electrolyte, but systems in a 1:1 electrolyte were also
      investigated. 

PMID- 24896881
TI  - An in situ approach for facile fabrication of robust and scalable SERS
      substrates.
AB  - The widespread implementation of surface enhanced Raman scattering (SERS)
      techniques for chemical and biological detection requires an inexpensive, yet
      robust SERS substrate with high sensitivity and reproducibility. To that end, we
      present a facile method to fabricate plasmonic SERS substrates with well
      distributed SERS "hot spots" on a large scale with reproducible SERS enhancement
      factors of ~10(8) for the Raman probe molecule 4-aminobenzenethiol (4-ABT). The
      SERS enhancement is attributed to the synergistic interactions between the strong
      plasmonic coupling among the assembled Au NPs and the structure-associated tip
      enhancement. Additionally, these mechanically-flexible substrates exhibit
      remarkably reproducible SERS signals, demonstrating the merits of our
      methodology. Our approach illustrates the potential opportunities for fabricating
      robust, commercially-viable SERS substrates with well-distributed "hot spots" on
      a large scale while avoiding costly vacuum deposition technologies. 

PMID- 24896882
TI  - Social rank and priority of access to resources in domestic fowl.
AB  - One of the most frequently encountered assertions concerning the concept of
      social dominance is that high rank confers priority of access to resources. There
      have been few systematic studies to document the reliability of this
      relationship. We report a recent study in which the hypothesis of close linkage
      between social rank and access to resources was tested. Five-bird single-sex
      flocks of domestic fowl representing four different stocks were observed for (1)
      determination of rank order among flock members, and (2) the frequency and
      duration of time each member had control of resources provided such that only a
      single bird would have access to a resource at any given time. These resources
      were feed, water, perch, nest box and dust-bathing litter box. The results of
      this study were: (1) competition among flockmates was manifest only at the
      feeder, (2) a significant overall relationship between social rank and frequency
      and duration of feeding was obtained, (3) within individual flocks, the higher
      ranking birds tended to have higher feeding measures, but in few flocks was the
      measure of rank congruent to the measure of feeding. In the most extreme case,
      both male and female flocks of one stock had a five-rank linear dominance
      hierarchy; in these flocks the 'feeding rank order' consisted of two tiers, with
      no feeding score differences among the top three socially-ranked birds and none
      between the two bottom social ranks. A second experiment tested the hypothesis
      that in flocks of five birds with a stable dominance hierarchy, no differences
      would appear in the expression of aggressive behavior directed to an introduced
      stranger (i.e. the 'control animal' hypothesis was tested). The results of this
      experiment were: in none of the five replicates did the alpha bird contribute the
      highest proportion of aggressive acts to introduced strangers. Second, third and
      fourth rankers showed highest scores depending on the flock. In domestic fowl,
      the alpha bird clearly does not have the 'control animal' role with respect to
      external sources of disturbance. Statements implying close linkage between social
      rank established by aggression and various global constructs such as priority of
      access to resources and defense of the group must be scrutinized with care. 

PMID- 24896880
TI  - Transmission geometry laserspray ionization vacuum using an atmospheric pressure
      inlet.
AB  - This represents the first report of laserspray ionization vacuum (LSIV) with
      operation directly from atmospheric pressure for use in mass spectrometry. Two
      different types of electrospray ionization source inlets were converted to LSIV
      sources by equipping the entrance of the atmospheric pressure inlet aperture with
      a customized cone that is sealed with a removable glass plate holding the
      matrix/analyte sample. A laser aligned in transmission geometry (at 180 degrees 
      relative to the inlet) ablates the matrix/analyte sample deposited on the vacuum
      side of the glass slide. Laser ablation from vacuum requires lower inlet
      temperature relative to laser ablation at atmospheric pressure. However, higher
      inlet temperature is required for high-mass analytes, for example, alpha
      chymotrypsinogen (25.6 kDa). Labile compounds such as gangliosides and
      cardiolipins are detected in the negative ion mode directly from mouse brain
      tissue as intact doubly deprotonated ions. Multiple charging enhances the ion
      mobility spectrometry separation of ions derived from complex tissue samples. 

PMID- 24896883
TI  - Behavioural comparisons of isolated, dominant and subordinate mice.
AB  - The study examines the suggestion that isolated male mice act in a similar way to
      dominant males. Behaviours of isolated, dominant and subordinate mice were
      compared in an open-field, emergence test, activity monitor and aggression test.
      In a number of ways the behaviour of both isolates and dominants differed from
      subordinates. Subordinates were more active on the first day in the open-field,
      but they habituated relatively quickly. In contrast, both the isolates and
      dominants were initially relatively inactive, but reacted to a novel situation
      for longer. There were, however, no circadian variations in activity in the three
      categories of mice. Unlike the subordinates, both dominants and isolates
      displayed aggression towards male mice; these last two categories of mice also
      had heavier sex accessory glands. It was concluded that the behaviour of isolated
      and dominant mice is very similar, at least under the conditions of this
      experiment. 

PMID- 24896884
TI  - Activite locomotrice de souris isolees, de deux lignees consanguines, dans un
      environnement semi-naturel ou en cages d'elevage.
AB  - Des enregistrements continus d'activite locomotrice ont ete effectues sur des
      souris males isolees des lignees Balb/c et C57bl/6, vivant en cages d'elevage ou
      en milieu semi- naturel. Les resultats montrent que les differences entre ces
      deux situations ne sont pas percues de la meme facon par les animaux des deux
      lign'ees: alors qu'en cages d'elevage les souris des deux lignees experiment la
      meme quantite totale d'activate, en milieu semi-naturel les souris Balb/c sont
      plus actives que les C57bl/6. En outre, l?s differences observees entre les
      lignees pour la repartition de l'activite au cours du nycthemere s'inversent
      lorsque l'on passe d'une situation a l'autre. L'etude de la variabilite fait
      aparaitre une dispersion plus grande des performances dans la lignee C57bl/6 en
      cages d'elevage, alors qu'en milieu semi-naturel la dispersion est plus chez
      Bal/c. 

PMID- 24896885
TI  - An attempt to separate the roles of corticosterone and ACTH in the control of
      post-shock fighting behaviour in male laboratory mice.
AB  - One experiment was conducted to separate the roles of corticosterone and ACTH in
      the mediation of the facilitatory effects of experiencing shock on subsequent
      fighting behaviour in male mice. It was found that (1) treatment with electric
      foot-shock and single injections of ACTH (one dose level) lead to comparable
      increases in subsequent fighting in intact males; (2) preventing changes in
      testosterone secretion by combined castration and testosterone replacement does
      not occlude or modify the facilitatory effects of shock or ACTH on subsequent
      fighting; and (3) preventing changes in both testosterone and corticosterone
      secretion by combined castration-adrenalectomy and testosterone-corticosterone
      replacement prevents shock and ACTH induced increases in fighting. These findings
      suggest that corticosterone plays a more important role than ACTH in the
      mediation of the facilitatory effects of shock on subsequent fighting behaviour
      in male mice. 

PMID- 24896886
TI  - Feeding, scanning and photophobia after local injection of pentobarbital or
      noradrenaline into the ventromedial hypothalamus.
AB  - Microinjections of pentobarbital or noradrenaline into the ventromedial
      hypothalamus (VMH) of ad libitum fed male Wistar rats promptly but transiently
      elicited feeding behaviour. No conspicuous differences were found between the
      effects of the two VMH-interventions on behaviour elements such as grooming,
      sniffing and locomotion. Scanning, however, was clearly depressed upon
      microinjection with pentobarbital. Subsequently, VMH-application of pentobarbital
      but not of noradrenaline was found to mitigate the animals' spontaneous aversion
      towards brightly illuminated areas. Therefore, it is tentatively suggested that
      the VMH contains a network for feeding and another non-noradrenergic one for
      responsiveness towards novel and fearful environmental stimuli. 

PMID- 24896887
TI  - Influence of the buck on social behavior of captive female fallow deer (dama
      dama) during the rutting season.
AB  - The behavioral interactions and grouping patterns of eight confined fallow deer
      (Dama dama) were observed during the rutting season to determine the influence of
      the buck on herd social organization and behavior. Data were collected on five
      does, two female fawns, and one male fawn under three conditions: (1) buck in the
      paddock, (2) buck not in the paddock but present outside of the paddock fence,
      and (3) buck absent. When the buck was in the paddock, all deer engaged in more
      non-agonistic social behavior. When the buck was absent, the aggressive behavior
      of the dominant does increased and was directed primarily at the subordinate
      does. The significance of male suppression of female-female aggression is
      discussed in regard to reproductive strategies. 

PMID- 24896888
TI  - Inter- and intraspecific sexual behavior in two species of macaque: A possible
      behavioral barrier to gene flow.
AB  - Adult male pigtail and rhesus monkeys have longer latencies for sexual responding
      to females of the other species than to females of their own species. Further,
      males of both species show testosterone rises when introduced to new conspecific
      females, but neither showed hormonal rises when introduced to extraspecific
      females. The rhesus males during the nonbreeding season for rhesus showed neither
      a hormonal rise nor any sexual behavior when introduced to cycling and receptive
      pigtail females. These data are used to argue that whereas cogeneric females may
      have some similarities with conspecific females, males are less attracted to
      them. Initial agonistic responses might preclude the long association requisite
      for the development of sexual behavior between extraspecific macaques and thus
      serve as a behavioral barrier to gene flow among sympatric macaques, which are
      physiologically freely interfertile. 

PMID- 24896890
TI  - Evolution and lateralization of the brain (Papers from a conference held by the
      New York Academy of Sciences, New York, N.Y., 12-15 October 1976). S.J. Dimond
      and D.A. Blizard (Editors). Annals of the New York Academy of Sciences, vol. 299.
      The New York Academy of Sciences, New York, N.Y., 1977, US$40.00 501 pp.

PMID- 24896891
TI  - Methods of inference from animal to human behaviour M. von Cranach (Editor).
      Aldine, Chicago, Ill., 1976, 390 pp., US$ 24.50.

PMID- 24896895
TI  - Temperature dependence of auditory thresholds in two Central European anurans,
      Bombina variegata variegata (L.) and Rana ridibunda ridibunda Pall. (Amphibia),
      and its relation to calling.
AB  - We recorded multi-unit activity from the torus semicircularis in two European
      anurans, to test for temperature dependence of the auditory thresholds. In Rana
      r. ridibunda the entire threshold-vs.-frequency curve shifts downward for a
      temperature increase from 5 degrees  to 15 degrees  C; the average increase in
      sensitivity is 14 dB. In Bombina v. variegata the increase in sensitivity
      averages 8 dB for a rise in temperature from 12 degrees  to 20 degrees  C; in
      addition, the best frequency is shifted by about 150 Hz by this increase in
      temperature, from 350-400 Hz to 550 Hz. The audiogram of Rana r. ridibunda
      differs from that of Bombina v. variegata in that it is markedly trimodal; the
      sensitivity maxima for Rana fall at 300-500 Hz, 750-1000 Hz and 1250-1700 Hz. 

PMID- 24896896
TI  - Open-field responses of domestic chicks in the presence or absence of familiar
      cues.
AB  - Male domestic chicks were reared in groups with distinctive cues (red crosses)
      placed on the walls of the home boxes from 2 to 7 d of age and their subsequent
      behaviour in an open field in the presence or absence of the familiar rearing
      cues was recorded. Ambulation, peeping, pecking, jumping and standing were all
      significantly higher and the latency to the first step, duration of freezing,
      sitting time, lying time and time spent with the eyes closed were significantly
      lower when the familiar rearing cues were present in the test situation. These
      observations are consistent with the suggestion that the birds are less fearful
      in the presence of familiar stimuli. The presence of the familiar cues also
      increased the time spent feeding and drinking. The preference effect was a
      specific one, for birds exposed to red crosses in early life preferred such
      stimuli to black circles in a subsequent two-choice situation, whereas chicks
      reared with black circles preferred them to red crosses. There was no
      generalisation of attachment from one stimulus to the other. As the chicks spent
      more time feeding and drinking in the presence of the familiar cues, it is
      assumed that fear was reduced. Thus, the results tend to confirm that the
      frequency of certain behaviour patterns is indicative of certain levels of fear. 

PMID- 24896898
TI  - Temporal relationships between shock treatment and intermale fighting behaviour
      in laboratory mice. Effects of modifying testicular and adrenal functions.
AB  - The three experiments of this series were conducted to (1) examine subsequent
      effects of electric shock on intermale fighting in previously isolated mice, and
      (2) determine to what extent post-shock fighting is affected by manipulations of
      the pituitary-gonadal and pituitary-adrenocortical axes. In experiment 1 it was
      found that shock treatment significantly increases fighting 1 2 to 1 h later.
      Experiment 2 showed that castration alone does not affect post-shock fighting,
      whereas adrenalectomy and castration combined with adrenalectomy both inhibit
      such fighting. Experiment 3 showed that pretreatment with testosterone increases
      fighting in intact males, but fails to restore post-shock fighting in
      adrenalectomized and castrated-adrenalectomized males. These findings suggest
      that (1) the pituitary-adrenocortical axis plays an important role in controlling
      post-shock fighting in mice, and (2) the inhibition of post-shock fighting by
      adrenalectomy and castration combined with adrenalectomy is not a result of the
      loss of adrenal testosterone which accompanies these operations. 

PMID- 24896897
TI  - Influence of gonadal hormones on the behaviour of pair-living Mongolian gerbils
      (Meriones Unguiculatus) towards the cagemate versus a non-cagemate in a social
      choice test.
AB  - Laboratory, semi-natural and field observations indicate that the Mongolian
      gerbil may naturally live in pairs or family groups. Endocrine influence on
      behaviour towards cagemates and non-cagemates was investigated. The males tested
      were intact or castrated. The hormonal condition of the females was controlled by
      gonadectomy and oestrogen and progesterone replacement treatment. The duration
      and number of visits to the incentive animals were recorded in a choice test,
      which allowed restricted contact between the experimental and incentive animals.
      Anoestrous females approached the intact cagemates more than the non-cagemates,
      while the intact males approached the non-cagemates more often. A comparison of
      the female behaviour under the different female endocrine conditions tested
      showed that females significantly increased their response in oestrus towards the
      strange intact males but not towards their cagemates. Experimental intact males
      analogously increased their response towards the strange oestrus female but not
      towards the cagemate. In tests which involved castrated males either as
      experimentals or incentives, no behavioural change was seen relative to the
      endocrine condition of the female. The hormonal effects seen were thus connected
      with the social relationship, as the hormone-induced changes were seen only in
      behaviour towards a strange animal. 

PMID- 24896899
TI  - Influences de la castration et du propionate de testosterone sur le comportement
      des rats conditionnes par paires.
AB  - Four groups of 10 male rats (Group A: normal rats, Group B: castrated rats, Group
      C: castrated rats + 1 mg P.T./day, Group D: castrated rats + 1 dose of 50 mg/kg
      of P.T. cyclohexane) were avoidance conditioned during nine sessions of 50
      trials. They were conditioned individually during sessions 4, 5 and 6 and by
      pairs during sessions 1, 2, 3, 7, 8 and 9. During these last sessions, all groups
      presented a low level of acquisition and aggressive behaviour. These phenomena
      were worsened in the castrated rats whose performances stayed low even when they
      were conditioned individually. On the other hand, the frequency of their
      aggressive behaviour was often higher than that of the other groups. The
      injection of P.T. cyclo-hexane improves the performance of the castrated animals
      but does not entirely compensate for the differences between control and
      experimental rats. 

PMID- 24896900
TI  - Activite operante et locomotrice chez des rats eleves dans des milieux
      differents.
AB  - Male and female rats of the inbred August and Fischer strains were reared during
      two months after weaning either in a standard laboratory environment (controls)
      or in a more complex environment (treated animals). The performance of these rats
      was measured afterwards in an operant conditioning situation with positive
      reinforcement. The multiple reinforcement schedule used included CRF and
      extinction periods. The treated animals, regardless of their sex or strain,
      displayed a higher response rate than the controls in both the CRF and extinction
      periods. This difference, however, appears only after several conditioning
      sessions and does not seem to be linked with the level of locomotor activity as
      measured by photocell actographic recording. The implications of the results are
      discussed. 

PMID- 24896901
TI  - Photoperiodic control of hibernation in Helix pomatia L. (Gastropoda: Pulmonata).
AB  - Different groups of Helix pomatia were exposed to short light pulses (1 or 2
      hours) during a long dark period (16 or 14 hours) of a 24-hour cycle of light and
      dark. The effect of the light pulses on the hibernation of the snails was shown
      to depend on the circadian time the pulses were introduced. Some of these light
      pulses reduced the hibernation. In other experiments groups of snails were
      exposed to 12-hour cycles or 24-hour cycles of equal periods of light and dark.
      Hibernation was reduced by the former as compared to the latter. These results
      show that Helix pomatia exhibits photoperiodic control of hibernation by a
      discontinuous or cyclic mechanism of time measurement. 

PMID- 24896902
TI  - Interrelationships of dominance and territorial behaviour in the pupfish,
      Cyprinodon variegatus.
AB  - Under laboratory conditions, Cyprinodon variegatus establishes either a dominance
      or territorial mating system. In the dominance system, one male usually has
      complete access to receptive females, while in the territorial system, several
      males have equal access. Four factors were observed to enhance a subdominant's
      ability to establish a territory and improve his reproductive success; increasing
      the number of conspecific intruders, increasing the available area, the presence
      of partial barrier, and the presence of a receptive female. 

PMID- 24896906
TI  - Children and their pet dogs : How they communicate.
AB  - The research of ethologists has provided a better understanding of the
      mechanisms, role and development of communication behaviour between young
      children and their peers. However, little is known about the communication
      systems between children and their pets. A study of these relational systems
      would be needed to understand how the child interacts with his whole environment.
      The present study is based on the analysis of video tapes filmed during
      spontaneous interactions between children from 2 to 5 years of age with their pet
      dog (N = 45) in their home environment. Inventories were made of the child and
      dog behaviours during these interactions. The results have shown the different
      dog behaviours induced by the child and the different child behaviours induced by
      the dog. The links between these behaviours and the variables which characterize
      both partners (age, sex, etc.) were treated by factor analysis of
      correspondences. These data are discussed in relation to the behavioural
      inventories of children and dogs with their peers and conspecifics. 

PMID- 24896907
TI  - Dynamics of nest defense by male centrarchid fish.
AB  - Field observations were conducted on four species of nesting male centrarchids to
      determine if guarding males discriminate intruders with respect to their
      potential threat to the brood, their size or position in the water column, or by
      the stage of the nest. Results demonstrated that bluegill (Lepomis macrochirus)
      and pumpkinseed (L. gibbosus) sunfish were the most frequent intruders and were
      attacked the most often. Nest guarding male largemouth bass (Micropterus
      salmoides) attacked intruders further from the nest and had the highest
      probability of attack of the four species studied. Rock bass (Ambloplites
      rupestris) males had the shortest distance of attack and one of the lowest
      probabilities of attack. Male black crappie (Pomoxis nigromaculatus) and
      pumpkinseed were intermediate in both responses. For all species, the size of
      intruder did not influence attack distance but larger males had a greater attack
      distance than smaller males. The distance of attack was greatest during the
      period immediately after hatch. These findings indicate species-specific
      differences in nest defense and males did discriminate intruders, possibly on
      their potential threat to the brood. The defense of the nest was related to nest
      stage, a finding which supports current theory of parental care. 

PMID- 24896908
TI  - Stimulatory effects of the noradrenergic neurotoxin DSP4 on sexual behavior in
      male quail.
AB  - Four separate experiments were carried out to test in castrated male Japanese
      quail the effects on testosterone-induced sexual behavior of the neurotoxic drug
      N-(2-chlorethyl)-N-ethyl-2- bromobenzylamine hydrochloride (DSP4). In each
      experiment, DSP4 enhanced some aspects of the testosterone-induced sexual
      behavior. The latency between the start of testosterone treatment and the first
      occurence of copulatory behavior was decreased, the behavior frequency and
      duration were increased, and the latency between the introduction of a stimulus
      female and the first sexual behavior was decreased. The effects could be reversed
      by concurrent treatment with the alpha-adrenergic agonist, phenylephrine. The
      stimulatory effects of DSP4 on behavior were not seen in castrated birds which
      did not receive a concurrent treatment with testosterone and they were associated
      with a significant decrease of the norepinephrine concentration in the
      hypothalamus. These results suggest that the noradrenergic system plays an
      inhibitory role in the control of copulatory behavior of quail similar to what
      has been described in the ring dove. 

PMID- 24896909
TI  - Manipulative motor activity of the cuttlefish Sepia Officinalis during prey
      capture.
AB  - Following capture by the cuttlefish Sepia officinalis , crabs are manipulated by
      active movements of all eight arms to facilitate prey paralysis and ingestion.
      This manipulative behaviour is described for the first time. Prior to ingestion
      the prey is regularly held in a specific orientation, termed the "reference
      position", irrespective of the initial angle of attack. Prey capture is followed
      by an initial, very rapid manipulative phase, bringing the cephalo-thorax-abdomen
      junction of the crab to lie adjacent to the mouth of the cuttlefish. In this
      position the cuttlefish can inflict a wound, usually to the proximal joints of
      the hind pereiopod. The salivary toxins are probably injected into this wound
      provoking a rapid paralysis of the prey. A second manipulative phase orientates
      the crab into the "reference position". This phase involves complex coordinated
      movements of the arms that can, in some cases, rotate the crab by up to 180
      degrees . Suppression of visual input has little effect on this behaviour.
      Tactile input concerning the position and movements of the pereiopods would
      appear to play an important role in the execution of this manipulation. Sensorial
      control of this behaviour and the possible existence of muscular receptors
      capable of detecting movements are discussed. 

PMID- 24896910
TI  - Multiple exposures to adult males and reproductive activation of virgin female
      Microtus Ochrogaster.
AB  - Virgin female Microtus ochrogaster living in family groups were reproductively
      activated by twelve 1-hr exposures over a 3-day period to unrelated sexually
      experienced males. Reproductive activation among virgin females receiving six or
      eight exposures over a 2- or 3-day period did not differ significantly from that
      of unexposed control females. Thus, frequent multiple exposures to unfamiliar
      males (and repeated stimulation by a male urinary chemosignal) can override the
      reproductive suppression typically experienced by virgin females remaining in
      family groups. 

PMID- 24896911
TI  - Latency measures indicate new place neophobia in Rattus species.
AB  - Latency to enter an unfamiliar wooden alley from the home cage was recorded on
      successive daily trials in several populations of domestic rats. All groups
      showed a decline in latency over days suggesting an initial neophobia. Latencies
      for individual rats on Trial 1 showed a bimodal distribution in most groups,
      reflecting mild or intense avoidance of the unfamiliar area. Earlier reports of
      new place reactions in wild Rattus suggesting an immediate neophilic reaction to
      a novel area may have overlooked initial hesitations to enter the area because
      latency measures were not used systematically. 

PMID- 24896912
TI  - Colony recognition of larvae by young workers of Cataglyphis Cursor (Hymenoptera,
      Formicidae ).
AB  - In an ant, C. cursor , colony recognition of larvae exists in callow workers 10
      days or older, but the discrimination capacities of very young workers has not
      been investigated. We show that workers less than 24 h old are already able to
      discriminate homocolonial from alien larvae. This is an additional argument in
      favour of the existence of a learning period for colony recognition of larvae
      during the preimaginal life. 

PMID- 24896913
TI  - Apes of the world. Their social behavior, communication, mentality, and ecology
      By Russell H. Tuttle. Park Ridge, New Jersey: Noyes Publications. pp. i-xix, 1
      421, 1986, $55.00, hardbound.

PMID- 24896917
TI  - Splitting in Presbytis entellusgroups.
AB  - Four bisexual groups (three multimale and one unimale) of Presbytis entellus were
      observed from September, 1985 to April, 1987. The multimale groups were found at
      areas where there was high density of monkeys as compared to area where the
      unimale group was found. These four groups split only after a takeover by a
      member of an all-male group. Each of the three multimale groups divided into one
      unimale and one all-male group. The all-male groups which caused these splits
      left the area after one of their members took over the bisexual group. The all
      male groups which were formed due to division of multimale groups remained in the
      same area. The split in the unimale group was again caused by interaction with an
      all-male group and resulted in the formation of two unimale groups; the younger
      females went with a new male and the older females remained with their original
      male. The splitting coincided with mating periods. The splitting of multimale
      groups took less time as compared to the splitting of the unimale group. The
      details of the splitting process are described. The present observations support
      Hrdy' s hypothesis (1977a) that Presbytis entellus maintain a unimale grouping
      and that the groups undergo three stages of development which turn them into age
      graded multimale groups, followed by a split which returns them to unimale
      grouping. 

PMID- 24896918
TI  - Emergent simple discrimination in children: role of contiguity.
AB  - Sixteen five- to seven-year-old children were exposed to two colour-form
      compounds. The compounds were presented successively. Pointing to the compounds
      was reinforced. Eight children received compounds A1B1 and A2B2; the others A1B2
      and A2B1. This task was mixed with a two-choice discrimination task that provided
      the colours A1 and A2 simultaneously. Colour A1 was correct for four children in
      each group. Finally, tests were given that offered a choice between forms B1 and
      B2, without A1 or A2. The children preferred the form that had been paired with
      the correct colour of the two-choice discrimination task. The results can be
      explained with the assumption that functions transfer between stimuli if the
      stimuli occur contiguously. This assumption also accounts for transfer of
      functions between stimuli paired in matching-to-sample tasks. 

PMID- 24896919
TI  - Behavioural development and adaptation: an assimilation of some of Waddington's
      ideas?
AB  - The paper discusses how ontogeny may contribute to the evolutionary processes
      dependent upon natural selection, as well as some of the answers that have been
      given to this essential question. The problem is addressed in relation to
      "instinctive" behaviour (maternal care) and to its evolutionary modification. The
      paper more particularly presents Waddington's contribution and the usefulness of
      his concept of "genetic assimilation". The conditions under which a specific
      adaptation might have evolved in the course of such a natural selective process
      are discussed. Finally, the constant reference to an epigenetic conception of
      phenotype (behaviour included) appears to be the Waddington's main contribution
      to evolutionary biology (ethology included). 

PMID- 24896920
TI  - Peripheral anosmia and display of lordosis behaviour in the male rat.
AB  - The current study was designed to investigate the effects of peripheral anosmia
      on the display of lordosis behaviour in orchidectomized rats primed with
      oestradiol benzoate and progesterone. Peripheral anosmia was induced by
      intranasal Zn SO4 application in rats trained to locate a food pellet buried
      under shavings. The willingness to mate - proportion of animals displaying
      lordosis responses to mounts of a stimulus male - did not differ in the anosmic
      animals and in saline controls. In contrast the sexual performance - lordosis
      score - appeared to be significantly increased in anosmic animals. The sexual
      performance was thus concluded to be modulated by the main olfactory system. 

PMID- 24896921
TI  - The predictability and patterns of vigilant behaviour.
AB  - While foraging, many animals alternate between feeding and scanning. Spectral
      analysis of continuous series of scan durations S and inter-scan intervals I for
      American Goldfinches Carduelis tristis, feeding either on small or large seeds,
      and choughs Pyrrhocorax pyrrhocorax showed that there were nonrandom fluctuations
      in the magnitude of S and I is all the examined series. Both the I and S showed
      cyclical oscillations between short and long events. Within individuals the
      sequential and temporal patterns in the I and S series were similar. However, the
      temporal patterns were more affected by variations in food-handling time than
      were the sequential ones. The predictability of the I and S series and the
      similarity, within individuals, of their sequential and temporal patterns seem
      general processes resistant to variations in behavioural constraints, and the
      temporal patterns in the I and S series fit to the method of handling food. 

PMID- 24896922
TI  - Maximizing reinforcement rate on spaced-responding schedules under conditions of
      temporal uncertainty.
AB  - The problem of finding the response strategy that maximizes reinforcement rate
      under differential-reinforcement-of low-rate (DRL) schedules, when emitted inter
      response-time (IRT) distributions have some variance, is considered. In general,
      if IRT distributions are generated so that their standard deviation remains a
      constant fraction of the mean IRT, then linear overestimation of the DRL schedule
      value is the optimal strategy, with the degree of overestimation which is optimal
      depending on the degree of temporal uncertainty, but generally being in the
      region of 10-20%. If the mean of emitted IRT distributions underestimates the
      schedule value, the reinforcement rate obtained is below maximal, and increases
      in IRT distribution variability actually increase obtained reinforcement rate.
      Thus, in conditions in which underestimation is forced, the DRL schedule may
      discourage accurately-regulated timing. Various satisficing policies producing
      25, 50, and 75% of the maximum obtainable reinforcement rate) will lead to linear
      underestimation of the schedule value. Experimental data showing both linear over
      and under-estimation can be found in the experimental literature. In general,
      therefore, deviations from accurate timing of behaviour on DRL schedules may not
      be the result of inaccuracies of underlying timing processes, but may occur
      because of maximizing or satisficing reinforcement rate. 

PMID- 24896923
TI  - The effects of contrast and position on habituation to models of predators in
      eastern banded killifish (Fundulus diaphanus).
AB  - We investigated habituation in killifish (Fundulus diaphanus) to repeated
      exposure of predator models of varying shades in two positions (above and below)
      against backgrounds of varying shades. Killifish that had habituated to a model
      of a given shade recommenced responding to a model of a different shade when the
      contrast between the second model and its background was greater than that of the
      first. They showed no increase in response to a model-background combination of
      lower contrast (Experiment 1). After a single presentation of one model
      background combination (i.e. minimal habituation and sensory adaptation) an
      increase in contrast again resulted in an increase in response, and a decrease in
      contrast resulted in a lower response (Experiment 2). The killifish reacted to
      models which were presented above the shoal following presentations below the
      shoal, but not if the order was reversed. This difference was found with models
      darker or lighter than the background (Experiment 3). These results were
      interpreted in relation to the predators present in the environment in which the
      killifish live, and the visual mechanisms with which the killifish perceive these
      predators. 

PMID- 24896924
TI  - The effects of an intramaze cue search rule on rat's spatial working memory.
AB  - Two groups of rats were trained in an elevated 8-arm radial maze consisting of
      four smooth and four hardware cloth covered (grid) arms. Rats in one group
      (Texture Relevant) had to enter four baited arms of one texture, Set A, before
      they could be rewarded for entering the second set of arms of the other texture,
      Set B. Rats in the other group (Texture Irrelevant) were not constrained in their
      pattern of arm selection. Rats in both groups were run in the maze until they had
      sampled all baited arms. Although Texture Relevant (TR) rats initially made more
      reentries than Texture Irrelevant (TI) rats during the first training phase, rats
      in both groups reduced reentries to equivalent, low asymptotic levels. TR rats
      also made many premature entries to Set B arms during initial training but
      reduced these errors with continued training. When adjacent arms became less
      spatially differentiated with reference to extramaze room stimuli in the second
      phase and in a replication of this experiment, TI rats increased reentries to
      earlier sampled arms more than TR rats. TR rats, however, increased premature
      entries into Set B when arms within each texture set became less spatially
      differentiated with respect to extramaze room stimuli. These results indicate
      that TR rats developed a stable hierarchical representation of the maze, which
      enhanced their retention of earlier visited arms in more difficult maze
      configurations. 

PMID- 24896925
TI  - Choice in a self-control paradigm: effects of reinforcer quality.
AB  - Pigeons were exposed to a self-control paradigm in which they chose between
      larger, more delayed and smaller, less delayed reinforcers. Reinforcer quality
      (i.e., the type of grain associated with each alternative) was varied across
      conditions. Choice behavior was influenced by grain quality; proportions of
      responses for the larger, more delayed alternative changed as a function of the
      grains associated with the response alternatives. Furthermore, the percentage
      deviation from mean baseline response proportions generally decreased as a
      function of the relative grain types associated with each response alternative.
      Manipulation of reinforcer quality can significantly influence the degree of self
      control typically exhibited by pigeons. 

PMID- 24896926
TI  - Le systeme reproductif chez une ponerine sans reine: Dinoponera quadriceps
      santschi.
AB  - Thirteen colonies of Dinoponera quadriceps were studied in the field in Brazil.
      Dissection of all workers showed that each worker has ovaries with 6
      ovarioles/ovary and a functional spermatheca. Moreover, the continuity of ovarian
      physiological states among workers is remarkable. Egg laying is performed by
      mated worker ( = gamergates) but also by few unmated ones exhibiting completely
      developed ovaries with numerous oocytes and yellow bodies inclusions. Besides,
      some gamergates present uncompletely developed ovaries and thus cannot be
      involved in egg laying until their ovaries reach full development. The role of
      both insemination and aging process in the differentiation between reproductive
      and non reproductive status is discussed. 

PMID- 24896927
TI  - Further support for the "drift" model of pigeons' short-term memory for spatial
      location.
AB  - The Drift Model is a conception of animals' short-term memory process as
      manifested in tasks such as delayed matching to sample. The model has four main
      assumptions. First, an attention focus or pointer moves through memory space
      representing the information that must be remembered. Second, during sample
      presentation, the pointer migrates in the direction of memory space representing
      the sample. Third, during delays (i.e., retention intervals), the pointer drifts
      in a random walk manner through memory space. Fourth, during the choice phase,
      subjects choose the alternative in memory space closest to the pointer. The model
      successfully accounts for many aspects of rats' (Roitblat & Harley, 1988) and
      pigeons' (Wilkie & Kennedy, 1987) short-term memory for spatial location. In the
      present research two explicit predictions were derived from the model, tested
      using pigeons in a delayed matching of key location task, and confirmed. 

PMID- 24896928
TI  - Detection of time-inhomogeneity in behavioural processes: tests for multiple
      abrupt changes in boutlengths.
AB  - Behavioural records often contain inhomogeinities. The number of such changes is
      usually not known beforehand. In this paper a description is given of parametric
      as well as non-parametric methods to determine the number of abrupt changes in
      which have been published in several papers in the biological and statistical
      literature have been gathered and completed here. The use of the test procedures
      is illustrated by means of examples. 

PMID- 24896929
TI  - [Not Available].
AB  - Recent ethological studies on the interactions between man and his pet dog, have
      shown different analogies between the behavioural mechanisms developed during
      intraspecific and interspecific proximal relationships. This study characterizes
      new analogies between sniffing, licking and rubbing behaviours of familiar dogs,
      directed towards the urban environment, their conspecific and their master. The
      results emphasize the importance of the synergic relation between the exploratory
      sniffing and tasting behaviours. Different hypothesis are put forward concerning
      the functions of these behaviours developped by dogs during their social
      interactions and their importance in relations between humans and animals. 

PMID- 24896930
TI  - Self-control and social cooperation.
AB  - Participants repeatedly played a self-control game in which choice of the higher
      of two monetary rewards on the present trial reduced the overall reward ('alone
      condition'). Other participants played a prisoner's dilemma (social cooperation)
      game in which choices alternated so that overall reward-reducing consequences of
      choosing the higher current amount were experienced by the other player
      ('together condition'). Participants playing the self-control game chose the
      lower current amount (and higher overall reward) significantly more frequently
      than did those playing the social cooperation game. In a second phase, half of
      the subjects who had played the self-control game played the social cooperation
      game and vice-versa. Little or no transfer was observed between conditions. In a
      second experiment, raising the amount of the next-trial reward increased self
      control but not social cooperation. Some transfer between self-control and social
      cooperation was observed. The crucial variable responsible for participants'
      better performance (closer to optimization) in the self-control game compared to
      the social cooperation game may have been the higher probability in the former
      that choice of the lower reward on the present trial would be repeated on
      subsequent trials. 

PMID- 24896931
TI  - Inter-individual distances during open-field tests in Japanese quail (Coturnix
      japonica) selected for high or low levels of social reinstatement behaviour.
AB  - Inter-individual distances (IIDs), during open-field tests, were measured in
      single sex pairs of quail of lines divergently selected for high (HSR) or low
      (LSR) levels of social reinstatement (SR) behaviour. Tests were carried out when
      the chicks were 1-, 3- and 6-weeks of age. IIDs were established within 1 min and
      remained stable thereafter. In HSR and mixed line pairs, but not LSR line pairs,
      IIDs increased with age. IIDs were shorter in HSR line pairs than in LSR or mixed
      line pairs at 1- and 3-weeks of age but not at 6-weeks of age when IIDs were
      similar in all pair-types. At 1- and 3-weeks of age, IIDs in mixed line pairs
      were intermediate to those in HSR and LSR line pairs. The sex of the pair-members
      did not influence IIDs. Previous studies have shown that selection for SR
      behaviour, in quail chicks, has effects that persist into later life and
      influence characters not present in the birds' behavioural repertoire at the time
      of testing for the purposes of selection. Such behaviour patterns include
      aggression, sexual behaviour and socio-sexual proximity behaviour. All of these
      behaviour patterns are expressed at higher levels in HSR line birds than LSR line
      birds. Differences in IIDs between HSR and LSR line birds may, therefore, be due
      to an interaction between environmental and genetic effects. In young HSR chicks,
      social reinstatement is the primary motivation and IIDs are short. However, as
      the HSR line chicks' age, IIDs reflect an interaction between social attraction
      and aggression related avoidance behaviour that tends to increase IIDs. In LSR
      line chicks aggression and social motivation are low at all ages and IIDs tend to
      remain stable. 

PMID- 24896932
TI  - Nursing behaviour and mother-lamb relationships in mouflon under fluctuating
      population densities.
AB  - The mouflon population of the subantarctic Kerguelen archipelago undergoes
      periodic die-offs and shows marked interannual variations in density. This
      situation allowed us to investigate nursing behaviour and mother-lamb
      relationships under contrasting population densities during three successive
      years, centred on a crash year (1992). Poor diet quality and high neonatal
      mortality characterised the pre-crash year (1991). During the crash year,
      neonatal mortality was high at the onset of the lambing season, but young
      survival increased rapidly when environmental conditions improved. Diet quality
      was high and neonatal mortality was reduced in 1993 (post-crash). Total suckling
      duration was constant between years, but the higher frequency of unsuccessful
      suckling attempts and allosuckling attempts in 1991 suggested a limitation of
      maternal expenditure for that year. Lambs grazed earlier, played less, spent less
      time resting and had lower growth rates in 1991 than in other years. These
      results suggest a greater mother-offspring conflict when food resources were
      limited. Adverse environmental conditions may affect females' condition and
      constrain maternal expenditure. However, maternal expenditure increased as soon
      as diet quality improved, suggesting that females adjusted maternal care by
      tracking environmental conditions. 

PMID- 24896933
TI  - Why do male ICR(CD-1) mice perform bar-related (stereotypic) behaviour?
AB  - Prolonged interaction with cage bars by captive mammals (usually classed as
      stereotypic) may reflect poor welfare. Such behaviour may arise from motivation
      to investigate the external environment or to escape captivity. However, these
      hypotheses have not been explicitly tested. We raised mice, Mus musculus, to
      adulthood in modified laboratory cages with two sets of bars at the top and side
      of the cage. One set provided a potential escape route, and half of each set was
      backed by Perspex to reduce cues from the external environment. We predicted
      where mice should interact with the bars according to their motivational
      priorities. Body weights were recorded weekly to study the relationship between
      physical development and bar-related behaviour. Serum corticosterone was measured
      to monitor the effect of bar-related behaviour on stress physiology. Mice
      preferred to interact with bars where external cues were detectable. As adults,
      mice responded more to the bars providing a potential exit, though this was
      affected by the exit location. Corticosterone titres were higher in mice whose
      potential exit was situated at the cage top. Response to the bars was apparently
      restricted by the physical development of mice, particularly among those whose
      potential exit was situated in the cage top. 

PMID- 24896934
TI  - Lateralization of trunk muscle volume, and lateralization of swimming turns of
      fish responding to external stimuli.
AB  - A significant bias towards right-hand startle C-bends was found in vibration
      stimulated zebra- and goldfish, but not in guppies and four Cichlid species. The
      goldfish right bias was significantly larger if they turned their head towards
      than away from the vibratory stimulus. In an undisturbed situation the fast
      swimming-turns of isolated goldfish and grouped zebrafish were significantly
      right-biased, especially so when attacked by group mates. In contrast, the slow
      turns were significantly left-biased, except for female zebrafish showing
      significantly right-biased slow turns during periods of non-attack by group
      mates. The contrast in left-right-bias between fast and slow turns may perhaps be
      explained by a white-muscle-mass bias to the right versus a red-muscle bias to
      the left, especially so in the anal region of the trunk of the zebrafish, because
      fast swimming is mainly powered by white muscle in contrast to red-muscle-powered
      slow swimming. Fish taxa that occur in open-water habitats and which are more
      often exposed to predatory fish might have evolved stronger muscular and
      behavioral lateralizations than more substrate-bound fish taxa. 

PMID- 24896935
TI  - Predatory behaviour in the ponerine ant, Centromyrmex bequaerti: a case of
      termitolesty.
AB  - Centromyrmex bequaerti is an African ponerine ant who nests in the termitaries of
      diverse Termitinae and Macrotermitinae and preys almost exclusively on their
      hosts. Such predatory specificity corresponds to a kind of familiarisation with
      the host species, because workers are able to capture other termites when
      experimentally accustomed. Hunting workers showed different capture behaviours
      depending on whether they were faced with a single termite worker or soldier, or
      a group of termites, and were particularly well-adapted to eliminate guarding
      termite soldiers. The strategy for capturing grouped termites was characterised
      by the recruitment of nestmates and the piling up of the paralysed prey before
      retrieving them to the nest. Using a group hunting strategy is considered another
      evolved feature for this termitolestic ant. 

PMID- 24896938
TI  - Prior residency and the stability of dominance relationships in pairs of green
      swordtail fish Xiphophorus helleri (Pisces, Poeciliidae).
AB  - The stability of dominance relationships between pairs of male green swordtail
      fish was followed daily for 20 consecutive days. In one experimental sample
      composed of 21 pairs, dominance of one of the fish had been favoured on the first
      day by giving the fish prior familiarity (prior residency) with the aquarium
      where it was to meet an intruder. In a control sample composed of 12 pairs, two
      intruders met in an unfamiliar aquarium. It was expected that the advantage given
      to the dominant by familiarity with the aquarium on the first day would disappear
      as the subordinate acquired in turn familiarity with the milieu. In comparison
      with pairs composed of two intruders, this would show up by more frequent
      inversions of the initial dominance relationship in pairs composed of a prior
      resident and an intruder. Only two inversions occured over the 20 days of follow
      up and they occured equally in the experimental (5%) and control (8%) samples.
      These results confirm the great stability of dominance relationships in dyads and
      invalidate the hypothesis that the prior residency advantage would decay as the
      subordinate became familiar with the aquarium. Unexpectedly, 13 of the 66 (20%)
      fish died over the 20 days. Death equally occurred in both samples but 12 (92%)
      cases implied initial subordinates. The exception was an initial dominant which
      had become the subordinate pair member three days before death. Various
      hypotheses are suggested to account for the selective deaths of subordinates. 

PMID- 24896939
TI  - Effet de la familiarisation avec l'environnement sur le comportement de vigilance
      de la tourterelle rieuse Streptopelia risoria.
AB  - An experiment on food-deprived barbary doves Streptopelia risoria shows that in a
      novel environment the subjects give priority to vigilant behaviour over foraging.
      The trade-off between vigilance and foraging is reversed when the subjects have
      been familiarized with their environment. Vigilance bouts are long and foraging
      bouts short in a novel environment, whereas the reverse is true in a familiar
      environment. These results, together with those of a previous study of the head
      movements of barbary doves (Cezilly and Brun 1989), suggest that the doves adjust
      their head movements (and therefore the duration of information gathering) to
      their familiarity with the environment. 

PMID- 24896940
TI  - Social play behaviour in young rhesus monkeys Macaca mulatta at three different
      ages: from the 3rd to the 6th month of life.
AB  - Social play behaviours were investigated in 17 young rhesus monkeys Macaca
      mulatta, belonging to a large captive group, at three ages: 3/4, 4/5 and 5/6
      months. Play initiatives were recorded (TO/BY) and the infants' partners were
      divided into five age groups (mothers, adults, similar-age infants, 1-yr-old
      infants and 2-yr-old infants). The findings suggest that mothers do not
      participate very much in the play initiatives of their offspring, but they do
      control it and, at an early age (3/4-4/5 months), they differentiate between sons
      and daughters. After this age, the infants seem to be more free in their choice
      of partners, even though infants appear to be more comfortable with their
      contemporaries rather than with infants of a different age. 

PMID- 24896941
TI  - L'apprentissage spatial du rat en situation de conditionnement operant.
AB  - Rats which have been conditioned up to 50 or 600 reinforcements with CRF.
      procedure are submitted to a modification of the position of the lever or the
      food hopper. We show the existence of a spatial orientation learning, starting
      with a direction learning given by the "objects" (lever, food hopper) of the set
      up and followed by a definite location learning. 

PMID- 24896942
TI  - Two issues in Pavlovian fear conditioning: selective fear of bright vs. dark, and
      CS determinants of CR form.
AB  - We examined the effects of tone, light, and dark conditioned stimuli (CSs) on
      barpress suppression and freezing in rats. We found more freezing to tone than to
      light or dark yet similar barpress suppression. In compound, the auditory and
      visual stimuli together evoked more suppression and freezing than did any element
      alone. The fact that the compounds could increase suppression speaks against a
      ceiling effect interpretation of the similar suppression to the elements. The
      data strengthen the growing evidence in fear conditioning that CSs in different
      modalities may evoke conditioned responses of different forms (freezing to tone
      vs. less freezing to light or dark) despite having similar associative values.
      The finding that light and dark produced similar levels of suppression and
      freezing argues against earlier claims (Welker & Wheatley, 1977) that rats are
      prepared to associate bright (but not dim) light with danger. 

PMID- 24896943
TI  - Equivalence class formation influenced by the number of nodes separating stimuli.
AB  - Two experiments examined whether the number of nodes separating stimuli
      influenced human subjects' conditional discrimination performances. In Experiment
      1, 3 college students were taught visual conditional discriminations among 2
      seven-member stimulus classes using a single-sample/two-comparison procedure.
      Following training, subjects were exposed to repeated probes for the emergence of
      derived relations separated by varying numbers of nodes. For all three subjects
      the results indicated that the order in which derived relations emerged was
      consistent with the number of nodes separating stimuli. The second experiment
      sought to extend Experiment 1 with four college students by teaching visual
      conditional discriminations among 3 seven-member stimulus classes using a single
      sample/three-comparison procedure. Results from the repeated probes in Experiment
      2 were similar to those of Experiment 1. The two experiments demonstrate that the
      number of nodes separating stimuli influences the order in which derived
      relations emerge during equivalence class formation. 

PMID- 24896944
TI  - Perceptual consequences of early social experience in precocial birds.
AB  - This article reviews recent work with precocial avian hatchlings demonstrating
      the important contribution that social experience with conspecifics can make to
      the development of species-typical perceptual preferences. In particular,
      experiments on the role of sibling social interaction in the development of early
      auditory and visually directed maternal preferences are surveyed. Results reveal
      that young hatchlings denied the opportunity for direct social experience with
      siblings consistently display auditory and visual preferences different from
      those shown by hatchlings allowed ongoing experience with their broodmates during
      the period immediately following hatching. Taken together, the studies reviewed
      here demonstrate that the perceptual preferences underlying the process of filial
      imprinting, long thought to be simply 'innate' or 'instinctive', are sensitive to
      an array of social factors present in the young bird's posthatching environment.
      The findings also provide support for the view that the minimum unit for the
      developmental analysis of species-typical behavior must be the developmental
      system, comprised of both the developing organism and its specific stimulative
      environment. 

PMID- 24896945
TI  - The regulation of maternal behaviour in marmosets and tamarins.
AB  - This article reviews a long-term investigation into the roles of (1) experience
      obtained with infants during development and postnatally, and (2) levels of
      reproductive-steroid hormones during late pregnancy, in the regulation of
      maternal caregiving motivation and behaviour in the red-bellied tamarin (Saguinus
      labiatus) and the common marmoset (Callithrix jacchus) (family Callitrichidae,
      Order Primates). Both observational studies, e.g. post hoc analysis of the
      relationship between developmental caregiving experience and infant-rearing
      success, and manipulative studies, e.g. direct analysis of the effects of sex
      steroid administration on maternal motivation, were performed. In red-bellied
      tamarins, a breeding female's infant-rearing success was related to its
      caregiving experience obtained during development and postpartum/postnatally. In
      multiparous females lacking developmental caregiving experience, postpartum
      maternal caregiving behaviour and infant-rearing success were related to
      prepartum urinary oestradiol levels. In nulliparous common marmosets, caregiving
      of infant-siblings increased as a consequence of physical interaction with parent
      infant dyads, late pregnancy, and exposure to late pregnancy-like levels of
      progesterone and oestradiol. The evidence for a dual mechanism of endocrine and
      experiential regulation of caregiving in these monkeys is discussed in terms its
      evolution and function. 

PMID- 24896946
TI  - Object-picture equivalence in the pigeon: An analysis with natural concept and
      pseudoconcept discriminations.
AB  - Pigeons were trained on a natural concept (food vs. non-food) and on a
      pseudoconcept (arbitrary classification of edible and not edible stimuli). The
      birds were trained with real objects and then tested with colour photographs in
      the object-to-picture transfer group, and they were trained and tested in the
      reverse order in a picture-to-object transfer group. The subjects showed good
      transfer of discrimination in both directions when the task involved a natural
      concept, but they did not show transfer of a pseudoconcept discrimination.
      Because all birds saw the same stimuli during the discriminative training, the
      difference in transfer was due to the type of classification of the stimuli.
      These results suggest object-picture equivalence based on functional
      classification. 

PMID- 24896947
TI  - Orientation and foraging movements in a patchy environment by the ant Serrastruma
      lujae (formicidae-myrmicinae).
AB  - Serrastruma lujae ants individually search for collembolans in the leaf litter of
      humid tropical forests. During the dry season, collembolans aggregate in wet
      patches randomly scattered in the dry litter where numerous single workers come
      hunting from their nest. We simulated this situation in the laboratory, and
      observed that workers seem to be able to use the humidity gradient direction to
      efficiently orient themselves towards a wet patch. Once the patch has been
      reached, they exhibit area-concentrated searching,consisting, in particular, of
      adopting a high sinuosity and a low speed. After capturing a collembolan, the
      ants return to their nest along nearly straight paths. This ability may rely on a
      spatial memory of the nest location by means of a path-integration process. In
      the absence of prey, however, various behaviours were observed after an
      unsuccessful search. Comparisons between these data and the results obtained with
      a homogeneously wet environment simulating the rainy season situation showed that
      these ants do not simply respond to the humidity level but are also sensitive to
      the degree of patchiness of their environment. They can therefore be said to be
      able to adapt suitably to the considerable climatic changes they encounter during
      the year. 

PMID- 24896948
TI  - Colour and pattern in relation to sexual and aggressive behaviour in the bluehead
      wrasse Thalassoma bifasciatum.
AB  - Terminal phase adult male bluehead wrasse show rapid and frequent changes of body
      colour from bright green to opalescent. Green body colour is associated with
      aggressive chases of other fish, opalescent with courting females and spawning
      and so the body colour gives an indication of the fish's 'intention' over the
      next few seconds. Pectoral fin spots appear during courtship and a hypothesis is
      suggested for their function. 

PMID- 24896949
TI  - Prototype identification and categorization of incomplete figures by pigeons.
AB  - Previous research has shown that pigeons, unlike humans, cannot identify
      prototypes after training with corrupted exemplars. In the present experiment,
      pigeons were initially trained to discriminate between examples of a degraded
      square and a degraded triangle. The pigeons then received a transfer test in
      extinction comprised of novel examples of the degraded square and triangle, and
      the prototype square and triangle. The pigeons successfully categorized both the
      novel examples of the degraded figures and the underlying prototypes. These
      results suggest that aspects of categorization and prototype identification may
      be shared across species. 

PMID- 24896950
TI  - Changing rates of reinforcement perturbs the flow of time.
AB  - This experiment tested the hypothesis that changes in rate of reinforcement
      affect the rate of an internal pacemaker as suggested by the Behavioral Theory of
      Timing (BeT: Killeen and Fetterman, 1988). Pigeons were trained to discriminate
      durations of 10 s and 20 s, and then exposed to higher or lower rates of freely
      delivered reinforcers. When returned to the discrimination task, judgments were
      reliably biased in the predicted directions: those returning from a richer
      context judged standard durations to be longer than did those returning from a
      poorer context. These results validate a key assumption of BeT, and provide an
      explanation of how changing tempos of life bias the perception of time. 

PMID- 24896951
TI  - A test of time-place learning in a cichlid fish.
AB  - This paper presents a test of time-place learning in fish. Convict cichlids,
      Cichlasoma nigrofasciatum, were offered food several times a day for 10-30
      consecutive days. A signal was given 1 min before each food presentation. If the
      food was always delivered in the same corner of the aquarium, the fish spent 66%
      of their time in that corner after the signal was given. But if the food was
      given in different corners throughout the day, each corner being associated with
      a specific daily time, the fish failed to show preference for the target corner,
      even after 30 days. Instead they learned which corners yielded food at any time
      of the day and visited these corners successively after the feeding signal was
      given. Failure to associate time and place may have been caused by a low cost of
      travel between corners, a limited number of rewards each day, and / or
      interference from learning the signal-food association. 

PMID- 24896952
TI  - Within-session discrimination between times of reinforcers in the minutes range
      by pigeons.
AB  - This experiment tested whether pigeons could discriminate between a large
      reinforcer delivered at 6 min (early) vs. 16 min (late) within a 20 min session.
      A within subject design was used in which an early reinforcer was delivered in
      one context, and a late reinforcer in another. Rate of responding on the first
      link of a chain schedule was higher in the early reinforcer condition.
      Furthermore, in probe sessions during which no large reinforcer was delivered,
      the discrimination was maintained. Implications for foraging are discussed. 

PMID- 24896954
TI  - Psychological distance to reward in monkeys.
AB  - A concurrent-chains schedule was employed to examine crab-eating macaques' choice
      between segmented and unsegmented fixed-interval 30-s schedules. A stimulus
      change occurred during one of the fixed-interval schedules (segmented schedule),
      while no stimulus change occurred during the other (unsegmented schedule). The
      subjects were exposed to three consecutive stimulus-change conditions, in an
      attempt to explore whether correlation of the stimulus changes with a fixed
      interval of nonreinforcement affects the preference between the alternatives.
      When the stimulus change always occurred at a half point of the segmented
      schedule (the first and third conditions), all subjects preferred the fixed
      interval schedule without stimulus changes. This replicated previous findings
      with pigeons and humans. On the other hand, when the intervals before and after
      the stimulus change varied on every entry to the segmented schedule with the sum
      of them being constant (the second condition), the subjects were indifferent to
      the alternatives. These results are consistent with the view that the preference
      for unsegmented schedules over segmented ones might be due to aversiveness which
      the initial component in the segmented schedule possesses as a result of its
      correlation with a fixed interval of nonreinforcement. 

PMID- 24896953
TI  - Attention to uninformative features expressed by pigeons in a duration matching
      to-sample task.
AB  - Pigeons were trained on a matching-to-sample task in which they had to respond to
      a different choice stimulus following the same durations (2 or 10 s) of two
      different signals. The duration signals consisted of a white light presented from
      the ceiling and a red light presented from the front wall. Subsequent test
      performance indicated that matching accuracy declined (1) when the set of choice
      stimuli following a duration signal differed from the set presented during
      training, and (2) when the color or location of the duration signal was changed
      from values used during training. These results are discussed in terms of
      attention to uninformative features of a visual stimulus. 

PMID- 24896956
TI  - Preference for own versus conspecific pups by inbred and outbred rats.
AB  - Communal care of young may occur when related females live in close proximity to
      each other. The degree of relatedness between females may affect discrimination
      of own from conspecific young. Retrieval tests were used to examine preference
      for own versus conspecific pups by inbred and outbred rats. Dams were given
      retrieval tests in a neutral arena every other day from day 1 through 10
      postpartum. Outbred, but not inbred, dams showed a significant preference for
      their own pups. Outbred dams also retrieved pups more slowly than did inbred
      dams. Differences in the behavior of dams and/ or similarity of cues presented by
      pups may be responsible for the lack of preference for own pups shown by inbred
      dams. The results of this study suggest that indiscriminate care of young should
      occur when closely related females share a nest. 

PMID- 24896955
TI  - Individual differences in responses of Norway rats to social induction of food
      preferences.
AB  - Each of 36 observer rats was: (1) exposed to a demonstrator rat that had eaten an
      unpalatable, cayenne-pepper-flavored diet (Diet Cay), then tested to determine
      its willingness to eat Diet Cay and (2) exposed to a demonstrator rat that had
      eaten a palatable diet (Diet NPT) to which the observer had previously learned an
      aversion, then tested to determine its willingness to eat Diet NPT. In both
      instances, some observers ate substantial amounts of the diet that their
      respective demonstrators had eaten, while other observers did not. No consistency
      was found across the two situations in the relative susceptibility of individual
      observer rats to social influences on their food choices. In a second experiment,
      observer rats interacted, at 3 day intervals, with demonstrator rats that had
      each eaten different diets. After each interaction, all observers were given a
      choice test to determine their preferences for the diet that their demonstrators
      had eaten. Again, there was no consistency in the relative strength of individual
      observer rats' socially induced preferences for diets fed to demonstrators.
      Stable individual differences in magnitude of susceptibility to social influence
      on food preference did not account for a detectable proportion of observed
      variance in diet selection. 

PMID- 24896959
TI  - The development of analysis methods for speech recognition.
AB  - This paper is intended to give an outline of the development and the state of the
      art in acoustical analysis of speech for recognition purposes. Starting with a
      short view on the pattern recognition problem in general, the paper shows how the
      spectral primary analysis will be more and more refined by including knowledge on
      the speech production and perception processes. Recognizers with high performance
      need a secondary analysis which produces feature vectors with components which
      are phonetically or articulatorically meaningful. Because it will be complicated
      to elaborate a more or less complete set of detectors, universal procedures are
      required for producing this description. Several approaches are discussed. 

PMID- 24896960
TI  - Developmental changes in the sequential behavior of interacting timber wolf pups.
AB  - We used information statistics to quantify first-order sequential dependencies in
      the social behavior of two sibling wolf pups (Canis lupus). Sequential
      dependencies in the behavior of the individual pups increased between the first
      sample (18-32 days of age) and two later samples taken from 34-53 days and 64-106
      days of age. Sequential dependencies between pups were greatest during the second
      age sampled. We relate these findings to changes in the importance and style of
      interactions. In the first 32 days, social co-actions primarily involved mutual
      mouthing and pushing. Between 34 and 53 days, when interactions frequently became
      aggressive, pups were most responsive to the actions of their partner and tail
      raising predicted biting. By 64 days, play-chasing was the mode. By this age pups
      had formed a relationship, were less attentive to the specific actions of their
      partner, and biting was no longer predicted by tail-raising. These results
      illustrate the importance of considering demand characteristics in distinguishing
      capabilities from performance, and suggest that changing social organization may
      underlie developmental changes in behavior. We also speculate that during these
      play-like interactions, pups may gain control over expressive displays. 

PMID- 24896961
TI  - Pigeon homing: The influence of topographical features in successive releases at
      the same site.
AB  - A new device, the direction-recorder, offered the possibility to extend earlier
      studies of homing behaviour of pigeons when relevant topographical elements
      (mountains and large tracts of water) interpose between the release site and the
      home loft. Three series of experiments were carried out at three different sites
      to investigate intraindividual and interindividual variability in subsequent
      tosses from the same locality. Two release sites were chosen behind a mountain
      chain with respect to home; at the third site homeward directed route crosses the
      sea. From our results it turns out that homing pigeons may adopt different
      strategies. Moreover, a wide intraindividual variability was observed in repeated
      tosses at the same site; some pigeons remained faithful to the first route,
      whereas other birds tried successive new routes which, in most cases, were
      significantly shorter than previous ones. This result indicates that pigeons try,
      and are actually able, to improve their performance in subsequent releases from
      the same site. 

PMID- 24896962
TI  - Searching in patches by European starlings, Sturnus vulgaris.
AB  - Despite the importance of within-patch search for predicting optimal patch
      leaving strategy, little experimental effort has been devoted to the study of
      this foraging behaviour. In addition, predators' strategic responses to
      variability in features like the within-patch distribution of prey can have
      important consequences for their dietary decisions. We therefore analyse the
      search paths of European starlings, Sturnus vulgaris, foraging individually in
      artificial patches that vary in the spatial distribution of buried prey in an
      outdoor aviary. The results demonstrate that the birds are searching differently
      depending on the order in which the experimental patch-types are experienced. We
      speculate that where the spatial predictability of prey is initially high the
      birds adopt a fixed search rule that results in area-concentrated search once a
      prey item is found, and performs well for both distributions encountered.
      However, where the predictability is initially low a more flexible strategy is
      adopted that results in increased area-concentrated search with experience of a
      patch type, independent of the actual within-patch distribution of prey. These
      findings suggest that starlings can use distinct strategies for different prey
      types, but they are classifying these types on subjective criteria that are
      difficult to predict from a priori reasoning. 

PMID- 24896963
TI  - Factors influencing pairbond stability in convict cichlids (Cichlasoma
      nigrofasciatum).
AB  - In isolated pairs of the biparental convict cichlid (Cichlasoma nigrofasciatum)
      caring for fry, pairbonds can be broken by removal of the fry. Within three
      hours, the mates of many pairs become so mutually aggressive that the female
      finally flees from her larger mate, who chases her. The pairbond is mended within
      seconds upon re-introduction of the fry. Yet removal of young leaves some pairs
      little or not at all affected. They seem to have more stable pairbonds. Multiple
      regression of data from 39 pairs on a quantitative measure of pairbond
      destruction revealed support for the so-called parity-hypothesis, which holds
      that a cichlid pair is compatible only when the female's aggressiveness
      compensates for her smaller size. The size of the female relative to the male's,
      and her aggressiveness relative to his in the undisturbed situation, proved
      positive predictors of pair stability in the fry stage. Thus the same factors
      which have earlier been shown to favour pair formation in other biparental
      cichlids seem also responsible for pair stability in a later stage of the
      reproductive cycle. 

PMID- 24896964
TI  - Demand curves for food in hens: Similarity under fixed-ratio and progressive
      ratio schedules.
AB  - Demand curves were generated for five domestic hens under progressive-ratio 5
      schedules of food delivery and under fixed-ratio schedules of food delivery that
      began at fixed-ratio 5 and were incremented by 5 each session. All sessions ended
      after 10 consecutive minutes without a response. Although response rates at a
      given ratio were higher under the progressive-ratio schedule, all hens completed
      higher ratios under the fixed-ratio schedule. Similar, but not identical, demand
      curves were generated under progressive-ratio and fixed-ratio schedules. Under
      both schedules, consumption (reinforcers earned) decreased as cost (ratio size)
      increased. Data generally were well described by an equation in which elasticity
      of demand is constant, although an equation in which elasticity could vary
      accounted for slightly more of the variance. 

PMID- 24896965
TI  - Effects of reinforcer type on rats' sensitivity to variation in reinforcer amount
      and reinforcer delay.
AB  - Twenty rats, divided into two groups, served as subjects in an experiment that
      examined choices between reinforcers that varied in amount or delay. One group
      received food reinforcers, and the other water reinforcers. No difference was
      found between the two groups in their values of sA (tendency of choice behavior
      to vary in accordance with variation in reinforcer amount). However, Group Food
      had significantly lower values of sD (tendency of choice behavior to vary in
      accordance with variation in reinforcer delay) than did Group Water, and Group
      Food's values of s As D (a measure related to self-control-choices of larger,
      more delayed over smaller, less delayed reinforcers) tended to be greater than
      for Group Water. Finally, over the session, sA and s As D showed no significant
      change, overall response rates decreased, and sD increased. Taken together, these
      results suggest that, independent of deprivation level, self-control for water is
      less than self-control for food. 

PMID- 24896966
TI  - Effects of number of alternatives on choice in humans.
AB  - The present study examined human choice between a task including a single
      alternative (i.e. a single-alternative task), and a task including multiple
      alternatives (i.e. a multi-alternative task). The subjects were divided into
      three groups and were exposed to three conditions. The multi-alternative task
      included two alternatives in two groups and included three alternatives in one
      group. An alternative in the single-alternative task was identical to one in the
      multi-alternative task. Amount of reinforcement for alternatives specific to the
      multi-alternative tasks was manipulated under three conditions in each group.
      When the amount of reinforcement was equal to or larger than that in the
      alternative common to both tasks, the subjects preferred the multi-alternative
      task over the single-alternative task. When amount of reinforcement was smaller,
      there was no difference in preference between the multi-alternative and the
      single-alternative tasks. In addition, the degree of preference for the multi
      alternative task depended on the number of alternatives that produced larger
      reinforcers. 

PMID- 24896967
TI  - Atomic layer deposition, characterization, and growth mechanistic studies of TiO2
      thin films.
AB  - Two heteroleptic titanium precursors were investigated for the atomic layer
      deposition (ALD) of titanium dioxide using ozone as the oxygen source. The
      precursors, titanium (N,N'-diisopropylacetamidinate)tris(isopropoxide)
      (Ti(O(i)Pr)3(N(i)Pr-Me-amd)) and titanium bis(dimethylamide)bis(isopropoxide)
      (Ti(NMe2)2(O(i)Pr)2), exhibit self-limiting growth behavior up to a maximum
      temperature of 325  degrees C. Ti(NMe2)2(O(i)Pr)2 displays an excellent growth
      rate of 0.9 A/cycle at 325  degrees C while the growth rate of Ti(O(i)Pr)3(N(i)Pr
      Me-amd) is 0.3 A/cycle at the same temperature. In the temperature range of 275
      325  degrees C, both precursors deposit titanium dioxide in the anatase phase. In
      the case of Ti(NMe2)2(O(i)Pr)2, high-temperature X-ray diffraction (HTXRD)
      studies reveal a thickness-dependent phase change from anatase to rutile at 875
      975  degrees C. X-ray photoelectron spectroscopy (XPS) indicates that the films
      have high purity and are close to the stoichiometric composition. Reaction
      mechanisms taking place during the ALD process were studied in situ with
      quadrupole mass spectrometry (QMS) and quartz crystal microbalance (QCM). 

PMID- 24896968
TI  - On sundials, springs, and atoms.
AB  - The orderly behavior that occurs when animals are required to deal with time
      requirements suggests the possibility that they have an internal clock that
      provides information about the duration of events. After discussing questions
      inherent in the concept of an internal clock and suggesting criteria that such a
      device should meet if it exists, data are reviewed involving several different
      types of experimental procedures. Every procedure produced different conclusions
      about the nature of timing. Such results, together with observations of behavior
      outside of the laboratory, suggest that an internal clock has not evolved and,
      furthermore, is not even necessary for animals to display temporal regularities
      in their behavior or to respond to temporal demands. 

PMID- 24896969
TI  - The influence of the scalar timing model on human timing research.
AB  - The scalar timing model has provided both a quantitative conceptual framework and
      experimental procedures for studying time perception in animals and humans. In
      the present paper, we document the impact of scalar timing on 'human' timing
      research. We also examine the reciprocal relationship, namely modifications to
      scalar timing that have resulted from human timing research. Finally, we identify
      issues in human timing that are not explicitly addressed by the scalar timing
      model. 

PMID- 24896970
TI  - A parsimonious alternative to the pacemaker/accumulator process in animal timing.
AB  - Models of animal timing often assume the existence of a pacemaker whose variance
      is produced by a Poisson process. Later stages in these models typically include
      an accumulator, additional sources of variance, and a process in which the
      accumulated value is compared to reference memory. Together, these stages produce
      a constant coefficient of variation (i.e. the 'scalar property,' often observed
      in experiments) even though at least one of the sources of variance is not
      scalar. We propose a more parsimonious source of scalar variance. We define a
      linear failure rate function and demonstrate that its resulting distribution
      function, called the Rayleigh distribution, always produces the scalar property
      without requiring: (a) additional sources of variance, or (b) that comparisons
      with reference memory always be based on ratios. Continuous and discrete versions
      of this model are derived. This model may serve as a more parsimonious pacemaker
      than others currently proposed and may replace the pacemaker/accumulator process
      in timing models. 

PMID- 24896971
TI  - Switching or gating? The attentional challenge in cognitive models of
      psychological time.
AB  - This paper briefly outlines theories dealing with attentional processes, before
      the status of attention is evaluated within cognitive models of psychological
      time. Particular emphasis is put on comparing the temporal information processing
      model (TIP) and the attentional gate model (AGM). It is argued that certain
      functional attributes that the AGM splits between an 'attentional gate' and the
      switch located at the clock level of the TIP model were already ascribed to the
      switch and supported by previous animal data. Thus, the notion of an 'attentional
      switch' is favored over adding a 'gate'. This does not exclude the possibility
      that the TIP model may be adapted to accommodate both prospective and
      retrospective timing data. 

PMID- 24896972
TI  - Time as content in Pavlovian conditioning.
AB  - Time has played only a limited role within the traditional theories of Pavlovian
      conditioning. Although temporal factors certainly contribute to whether
      conditioning occurs, the traditional assumption in the associative framework has
      been that associations lack temporal information. Recently, the temporal coding
      hypothesis has challenged that view, arguing that animals encode temporal
      relationships as part of associations. That is, proximal temporal relationships
      not only foster associative learning, but also are part of the content of
      learning. The present paper reviews for the nonspecialist the increasing
      empirical evidence that temporal coding is ubiquitous in Pavlovian paradigms,
      including simultaneous and backward conditioning, second-order conditioning,
      sensory preconditioning, cue competition, Hall-Pearce type CS-preexposure, and
      conditioned inhibition. The data support the temporal coding hypothesis' view
      that contiguity is sufficient for associative learning to occur, but challenge
      the central assumption of the informational hypothesis that predictive relations
      are necessary for learning to occur (as opposed to predictive relationships only
      being necessary for the expression of knowledge). 

PMID- 24896973
TI  - Are separate theories of conditioning and timing necessary?
AB  - Conditioning and timing studies have evolved under separate traditions, which is
      exemplified in both traditional theories (e.g. the Rescorla-Wagner model of
      conditioning vs. Scalar Timing Theory) and in a dual process model (Gibbon, J.,
      Balsam, P., 1981. In: Autoshaping and Conditioning Theory. Academic Press, New
      York.). Other lines of theoretical development in both timing and conditioning
      fields have resulted in the emergence of 'hybrid' theories in which conditioning
      and timing processes are integrated. Simulations were conducted with a recent
      hybrid theory of timing (Machado, A., 1997. Psychol. Rev. 104, 241-265). The
      simulations were of classical conditioning procedures in which the local or
      global predictability of food was varied by manipulating the variability of the
      CS-US relationship, variability of the CS duration, and variability of the
      intertrial interval. The hybrid model provided good qualitative fits to indices
      of conditioning (discrimination ratios) and timing (local rates of responding),
      indicating that it may be possible to model both conditioning and timing results
      with a single process in which an internal representation of time and a strength
      of association are integrated. However, the failure of the model to provide good
      quantitative fits of the data indicates the need for a consideration of
      alternative perceptual representations of time and/or principles of association
      within the framework of the hybrid model. 

PMID- 24896974
TI  - Timing behaviour of black-capped chickadees (Parus atricapillus).
AB  - In Experiment 1 the behaviour of black-capped chickadees timing intervals of 12.5
      or 37.5 s was studied using the peak procedure. Average rate of responding peaked
      near the trained FI on test trials, while the spread of the response distribution
      was larger for the longer FI. On individual trials, chickadees showed a break-run
      break pattern of abrupt changes in rate of responding. These results, plus the
      pattern of means, standard deviations, and correlations found in start times,
      stop times, and durations of runs, were similar to those found in pigeons and
      rats. This suggests that birds and rodents use similar timing mechanisms. In
      Experiment 2, chickadees were tested with an interrupted FI signal. On such 'gap'
      trials, the chickadees, like pigeons but unlike rats tested under similar
      parameters, ignored the signal time elapsed prior to the FI interruption and
      reset the interval clock. 

PMID- 24896975
TI  - The influence of 'switching' on the psychometric function in the free-operant
      psychophysical procedure.
AB  - Fifteen rats were trained under the 'free-operant psychophysical procedure',
      using a sucrose reinforcer. The training sessions consisted of 50-s trials in
      which reinforcers were available on a variable-interval 30-s schedule; in the
      first 25 s of each trial, reinforcers were only available for responses on lever
      A, whereas in the last 25 s they were available only for responses on lever B.
      Data were collected in probe trials (4 per session) in which no reinforcers were
      delivered, during the last 10 sessions of each phase of the experiment. In phase
      1 (70 sessions), repetitive switching between the levers was prevented by
      withdrawal of lever A after the first response on lever B in each trial. In phase
      2 (40 sessions), this constraint on switching was removed. In phase 3 (40
      sessions), it was reinstated. In all 3 phases, the response rates on lever A
      declined and the response rates on lever B increased as a function of time from
      the trial onset. The response rate on lever B, expressed as a percentage of the
      overall response rate, conformed to a two-parameter logistic function. Removal of
      the constraint on switching did not alter the indifference point (the time
      corresponding to 50% responding on lever B), but did reduce the slope of the
      function, this being reflected in an increase in the Weber fraction. The changes
      were reversed when the constraint on switching was reinstated. The results show
      that constraining switching altered the slope of the psychometric function; thus
      caution is needed in interpreting psychometric functions obtained with the free
      operant psychophysical procedure in terms of theoretical models of timing
      processes. 

PMID- 24896976
TI  - Temporal control in Pavlovian occasion setting.
AB  - Rats were trained with two Pavlovian serial feature positive discriminations (X
      >A+/A- and Y->B+, B-), in which the target stimuli (A and B) were reinforced when
      they were preceded by the feature stimuli (X and Y), but not when they were
      presented alone. In one discrimination the feature-target interval was 10 s, and
      in the other discrimination that interval was 30 s. In a series of tests in which
      the feature target interval varied in ten steps between 5 and 50 s, performance
      was better when the targets were presented at their usual training times after
      the feature, rather than earlier or later. Training with the shorter FTI (10 s)
      resulted in both greater peak responding at the training interval and steeper
      temporal gradients than training with the longer FTI (30 s). Presentation of a
      compound feature comprised of both the 10 s and 30 s feature elements shifted the
      time of peak target responding to an intermediate value, 15 s. In contrast,
      simple conditioning controlled by the features (measured in the empty intervals
      between feature and target presentations) showed temporal control but no evidence
      for stimulus averaging. Most of these results are consistent with scalar timing,
      but may imply separate temporal codes or timing mechanisms for simple
      conditioning and occasion setting. 

PMID- 24896977
TI  - Acquisition and extinction under periodic reinforcement.
AB  - This study reexamined the processes of acquisition and extinction under periodic
      reinforcement. During the first phase of the experiment, pigeons were exposed to
      a fixed-interval schedule either 40 or 80 s long. During the second phase, each
      session started with the fixed-interval schedule but changed to extinction at an
      unpredictable moment. The results showed that during phase 1 the curve for the
      average rate of pecking along the interval rotated across sessions, that is, the
      rate immediately after food decreased, whereas the rate at the end of the
      interval increased. The initial and terminal rates approached their steady state
      at different speeds. During the extinction trials of phase 2, behavior was
      characterized by pause-peck oscillations with a period slightly longer than the
      fixed-interval duration. These findings concerning acquisition and extinction
      under periodic reinforcement were then compared with the predictions of some
      current theories of timing. 

PMID- 24896978
TI  - Do pigeons show incidental timing? Some experiments and a suggested hierarchical
      framework for the study of attention in animal cognition.
AB  - Three experiments are reported that examine pigeons' ability to process
      incidental time cues when time cues are placed in compound with either a visual
      pattern cue or a spatial position cue. In experiments 1 and 2, it was found that
      incidental timing suffered relative to timing on control tests in which time-only
      cues were presented. However, these experiments did not involve explicit training
      to match duration when the carrier stimulus consisted of a visual pattern or
      spatial position. When such explicit training was given prior to testing in
      experiments 3A and 3B, it was found that pigeons matched time sample stimuli
      equally accurately when duration trials only were given throughout a session or
      were randomly intermixed with visual pattern or spatial position matching trials.
      It was concluded that pigeons can process time accurately while simultaneously
      processing a stimulus from another dimension. 

PMID- 24896979
TI  - Plasmonic nanoantenna arrays for surface-enhanced Raman spectroscopy of lipid
      molecules embedded in a bilayer membrane.
AB  - We demonstrate a strategy for surface-enhanced Raman spectroscopy (SERS) of
      supported lipid membranes with arrays of plasmonic nanoantennas. Colloidal
      lithography refined with plasma etching is used to synthesize arrays of
      triangular shaped gold nanoparticles. Reducing the separation distance between
      the triangle tips leads to plasmonic coupling and to a strong enhancement of the
      electromagnetic field in the nanotriangle gap. As a result, the Raman scattering
      intensity of molecules that are located at this plasmonic "hot-spot" can be
      increased by several orders of magnitude. The nanoantenna array is then embedded
      with a supported phospholipid membrane which is fluid at room temperature and
      spans the antenna gap. This configuration offers the advantage that molecules
      that are mobile within the bilayer membrane can enter the "hot-spot" region via
      diffusion and can therefore be measured by SERS without static entrapment or
      adsorption of the molecules to the antenna itself. 

PMID- 24896981
TI  - Quality control for building libraries from electrospray ionization tandem mass
      spectra.
AB  - Electrospray ionization (ESI) tandem mass spectrometry coupled with liquid
      chromatography is a routine technique for identifying and quantifying compounds
      in complex mixtures. The identification step can be aided by matching acquired
      tandem mass spectra (MS(2)) against reference library spectra as is routine for
      electron ionization (EI) spectra from gas chromatography/mass spectrometry
      (GC/MS). However, unlike the latter spectra, ESI MS(2) spectra are likely to
      originate from various precursor ions for a given target molecule and may be
      acquired at varying energies and resolutions and have characteristic noise
      signatures, requiring processing methods very different from EI to obtain
      complete and high quality reference spectra for individual analytes. This paper
      presents procedures developed for creating a tandem mass spectral library that
      addresses these factors. Library building begins by acquiring MS(2) spectra for
      all major MS(1) peaks in an infusion run, followed by assigning MS(2) spectra to
      clusters and creating a consensus spectrum for each. Intensity-based constraints
      for cluster membership were developed, as well as peak testing to recognize and
      eliminate suspect peaks and reduce noise. Consensus spectra were then examined by
      a human evaluator using a number of criteria, including a fraction of annotated
      peaks and consistency of spectra for a given ion at different energies. These
      methods have been developed and used to build a library from >9000 compounds,
      yielding 230,000 spectra. 

PMID- 24896982
TI  - An experimental model of aggressive dominance in Xiphophorus Helleri (pisces,
      poeciliidae).
AB  - An experimental model was constructed using seven postulates derived from the
      experimental results of Zayan (1974, 1975a,b,c, 1976). The model specifies the
      relative importance of several asymmetries in predicting aggressive dominance in
      Xiphophorus helleri . These asymmetries concern difference between duellists with
      respect to: prior residence in the tested area (vs intrusion); immediate social
      experiences of dominance or submission; social isolation; individual familiarity
      and recognition. The predictions of the general model were checked experimentally
      and confirmed; a multiple orthogonal regression accounted for about 97% of the
      variance in our experimental results. The basic experimental results serving as
      postulates were confirmed and could be generalized; a new synthetic and
      predictive model was formulated concerning the determinants of aggressive
      dominance in Xiphophorus . 

PMID- 24896983
TI  - Operant-Pavlovian interactions: The effect of the number of stimuli with free
      food depends on the operant baseline.
AB  - Four groups of three pigeons were trained to respond under operant schedules
      which varied with respect to response rate requirements and reinforcement
      frequency. The number of short duration stimuli preceding free food was
      manipulated in different experimental conditions. Operant behavior was maintained
      on one key, while stimuli were presented on another key. Stimulus key response
      rates, latencies to the first response on the stimulus key and the percentage of
      stimuli responded to did not vary as a function of the number of stimuli
      presented, but were dependent upon the reinforcement frequency of the operant
      baseline. 

PMID- 24896980
TI  - High affinity radiopharmaceuticals based upon lansoprazole for PET imaging of
      aggregated tau in Alzheimer's disease and progressive supranuclear palsy:
      synthesis, preclinical evaluation, and lead selection.
AB  - Abnormally aggregated tau is the hallmark pathology of tauopathy
      neurodegenerative disorders and is a target for development of both diagnostic
      tools and therapeutic strategies across the tauopathy disease spectrum.
      Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate
      affinity and specificity for tau would allow noninvasive quantification of tau
      burden using positron emission tomography (PET) imaging. We have synthesized
      [(18)F]lansoprazole, [(11)C]N-methyl lansoprazole, and [(18)F]N-methyl
      lansoprazole and identified them as high affinity radiotracers for tau with low
      to subnanomolar binding affinities. Herein, we report radiosyntheses and
      extensive preclinical evaluation with the aim of selecting a lead radiotracer for
      translation into human PET imaging trials. We demonstrate that [(18)F]N-methyl
      lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid
      brain entry in nonhuman primates, favorable kinetics, low white matter binding,
      and selectivity for binding to tau over amyloid, is the lead compound for
      progression into clinical trials. 

PMID- 24896984
TI  - Catalepsy in rats: Its inheritance and relationship to pendulum movements and
      audiogenic epilepsy.
AB  - Outbred Wistar rats were selectively bred for predisposition to catalepsy for 16
      generations. The rats predisposed to catalepsy are characterized by an increased
      (in an unselected control population) or decreased (in S13) motor activity,
      decreased defecation scores, and elevated blood pressure. Selective breeding for
      catalepsy for 16 generations resulted in the production of a stock with about 50%
      of the animals showing a consistent cataleptic reaction, versus about 10% in the
      control unselected stock. From segregation analysis it was concluded that
      predisposition to catalepsy is inherited as an oligogenic dominant characteristic
      with incomplete penetrance. The same seems to be the case with predisposition to
      pendulum movements. There is a positive phenotypical and genetic relationship
      between predisposition to catalepsy and predisposition to pendulum movements, and
      a negative relationship between predisposition to catalepsy and incidence of
      audiogenic seizures. A genetic model for the relationship between catalepsy,
      pendulum movements and audiogenic epilepsy is proposed. 

PMID- 24896985
TI  - Self-control revisited: Some factors that affect autoshaped responding.
AB  - Pigeons were exposed to autoshaping procedures under which 50% of red key
      illuminations were followed by 9-sec food deliveries, and 50% of blue key
      illuminations were followed by 3-sec food deliveries. When all key illuminations
      were 6 sec, pigeons preferred the red stimulus. Subsequent manipulations
      demonstrated that preference could be shifted to the blue stimulus by either
      increasing the duration of the red stimulus or imposing a delay interval between
      the offset of that stimulus and food delivery. A final experiment demonstrated
      that, in two of three subjects, preference for key illuminations associated with
      longer, but delayed, food deliveries generally increased as the duration of all
      key illuminations was lengthened. These results, obtained under conditions where
      keypecking had no programmed consequences, are similar to those previously
      observed under procedures involving a positive response-food dependency. 

PMID- 24896987
TI  - Extinction of conditioned defensive burying.
AB  - Rats were shocked once through a wire-wrapped dowel when they contacted it in a
      bedding-lined test chamber. Then the amount of conditioned defensive burying was
      measured for several days under extinction conditions; each of the rats was
      placed in the chamber for 15 min every 24 hr but no more shock was administered.
      The frequent bursts of burying directed at the dowel on the first test were
      almost totally absent by the fifth or sixth. Repeated exposure to the dowel
      conditioned stimulus was necessary for this extinction; neither the passage of
      time per se nor repeated exposure to the chamber in the absence of the dowel was
      sufficient to produce any significant decline in the tendency for the rats to
      push bedding at it. Making it impossible for the subjects to engage in burying
      behaviour during the extinction trials by removing the bedding from the test
      chamber did not affect the rate of extinction. 

PMID- 24896986
TI  - Saccharin preference of hamsters, gerbils and rats in the "two-food" situation.
AB  - Hamsters, gerbils and rats were randomly assigned to a diet that was either dry,
      moist or wet. Within each diet the animals were given access to either one that
      was saccharin-flavoured (varying from 0.1% to, 1.2%) or a plain one. The Williams
      Square design was used to assess the effects of different levels of saccharin on
      the relative intake of sweetened and plain diets. The results indicate that
      hamsters and gerbils were indifferent (show about 50% preference) to the presence
      of various Saccharin concentrations in both mash and powdered diets. When tested
      with a liquid diet, these animals were indifferent to low levels of the
      sweetener, but showed increasing preference for the plain diet when increasing
      levels of saccharin were placed in the sweetened diet. In contrast, rats showed a
      high preference for low levels of saccharin in a liquid diet and decreased
      preference at higher levels. When tested with mash and powdered diets, the rats
      were indifferent to low levels of saccharin but showed a preference for the plain
      diet as the saccharin level of the sweetened diet increased. In general, these
      results reveal that rats differ from hamsters and gerbils in their pattern of
      choice of sweetened and plain diets in the "two-food" situation. 

PMID- 24896989
TI  - Social facilitation in a 'non-social' animal, the centipede Lithobius forficatus.
AB  - In a series of experiments in which centipedes ran alone (control), with a
      passive audience, and in coaction (two together), on a simple escape runway,
      significant differences from controls in latency and running speed were observed
      under audience conditions. The relevance of this apparent demonstration of social
      facilitation in an animal which is essentially not social is discussed in
      relation to the Zajonc (1965) 'mere presence' and Cottrell (1972) 'evaluation
      apprehension' hypotheses of social facilitation. 

PMID- 24896988
TI  - The role of new flavors in the aquisition of odor aversion.
AB  - In two experiments rats received either an odor together with a flavor
      (experiment I) or with tap water (experiment II) prior to lithium chloride
      induced illness. The rats were then tested for the aversion of tap water in
      compound with the illness-paired odor offered together with an alternative new
      odor not paired with toxicosis. The two-odor-box-choice tests revealed that rats
      easily acquire an odor aversion even when the odor is not presented in a
      simultaneous compound with a new flavor and reject the drinking box, where the
      conditioned odor is presented, purely on the basis of that odor. Food Aversion
      Learning, Taste Aversion, Odor Aversion, Odor Potentiation. 

PMID- 24896990
TI  - Reinforcer frequency and reinforcer duration as biasers of signal detection.
AB  - Five pigeons were trained to discriminate a constant luminance difference when
      both reinforcer frequency and reinforcer magnitude were varied in an animal
      analogue of the human discrete-trial yes- no detection task. Variation of
      relative reinforcer frequency was more effective in biasing detection performance
      than variation of relative reinforcer duration. Stimulus discriminability was
      independent of both reinforcer frequency and reinforcer duration. 

PMID- 24896991
TI  - Changeover cost and switching between concurrent adjusting schedules.
AB  - Using pigeon subjects we studied the effects of changeover cost on rates of
      switching between concurrent adjusting variable ratio schedules. Each side-key
      schedule while activated increased with the delivery of each reinforcer and
      decreased with reinforcer delivery when the alternate key was active. With no
      changeover cost, changeovers were frequent although not optimal. Switching from
      one side-key to the other was reduced following the addition of a single center
      key changeover response, and reduced progressively further with increasing time
      (FI;FT), or response (FR;VR) requirements. This procedure is discussed as a model
      for the determination of variables which control a forager's giving-up in one
      food source patch and switching to another. 

PMID- 24896998
TI  - What motivates the food bringing behaviour of the peregrine falcon throughout
      breeding?
AB  - Wild peregrine falcon pairs (Falco peregrinus brookei) have been observed from
      courtship until fledgling stage. We analyse the typology of the food bringing
      behaviour and put forward explanations about the motivation underlying this
      behaviour throughout the breeding period. According to the stage of the breeding
      period and to the sex involved, the motivation underlying the food bringing
      behaviour is different. Until the fledgling stage, the possibility of a male
      reaching the young depends on the females' control: males transfer food to
      females in order to give food to the young. This study stresses the influence of
      male - female relationships upon the expression of the parental behaviour of the
      male peregrine. The dominance of the female over the male - linked to reversed
      sexual size dimorphism - should be necessary to 'manage' the duty schedule since
      it prevents the occurrence of conflicts harmful to the offspring. 

PMID- 24896999
TI  - Pup's broadband vocalizations and maternal behavior in the rat.
AB  - Rat pups emit broadband vocalizations with components extending from the audible
      to the ultrasonic range. Three experiments were undertaken to determine the
      circumstances under which the calls are emitted, and the effects that they might
      have on the maternal female's behavior. In the first study, pups were manipulated
      by the experimenter in several different ways. Broadband calling occurred when
      the pup was picked up and moved off the horizontal plane. In a second study, the
      mother was observed interacting with her litter. Vocalizations occurred most
      often when the mother engaged in behaviors that brought her into contact with the
      pups, such as nest entry, moving while in the nest, and pup licking. In another
      experiment, females were temporarily deafened. Relative to controls, deafened
      females engaged in more incidental contact with the pups, although only if the
      female was deafened during the first of two tests, when the pups were two days
      old. Broadband calling may function to reduce rough handling or inadvertent
      contact by the mother. 

PMID- 24897000
TI  - A new nonlinear model of mechanisms of motivation.
AB  - Models of motivation have been traditionally classified along the lines of
      homeostatic/ priming dichotomies using a diversity of definitions and names.
      Here, similar classification is used to describe a model of behaviour made of two
      well-defined mechanisms connected in series representing priming and homeostasis,
      and comparisons with well-known concepts in the field of animal behaviour are
      presented in order to show the advantages of this model in interpreting some
      problematical areas of animal motivation. The resulting model is analyzed as a
      Volterra nonlinear system and a simulation example is explained. 

PMID- 24897001
TI  - Anticipatory contrast and diet selection by pigeons.
AB  - The effect of future rate of reinforcement on choice and rate of responding was
      examined in three experiments in all of which pigeons performed on an operant
      simulation of diet selection followed by either a high or low rate of
      reinforcement. In Experiment 1 the duration of the prey selection task was 20
      min. A within-subjects design was used: in one operant chamber a high rate of
      reinforcement followed the session of diet selection, and in another chamber, a
      low rate of reinforcement followed. In Experiment 2 a between-subjects design was
      used with 8 min of diet selection and a stronger manipulation of rate of
      reinforcement. In Experiment 3, a within-subjects design was used with more
      highly discriminable operant chambers. The results on rate of responding were
      consistent with what is known about contrast: A weak contrast effect during the
      diet selection task was obtained in Experiment 1, a larger contrast effect in
      Experiment 3, and a conditioning effect was found in Experiment 2. The effect on
      choice was examined in Experiments 1 and 3 but was weak in both cases. The
      results suggest that the mechanism underlying contrast in choice and rate of
      responding are not one and the same. Foraging implications are discussed. 

PMID- 24897002
TI  - Gestalt and dynamic processes in decision making.
AB  - People sometimes prefer a sure gain to a risky but possibly larger gain, a
      tendency known as risk-aversion. On the other hand, they may prefer a possibly
      larger loss to a smaller sure loss, a tendency known as risk-seeking. Experiment
      1 showed that, by repeating the event, these tendencies could be substantially
      reduced, but not eliminated, when expected value was held constant between the
      sure alternative and the risky one. Experiment 2 demonstrated that risk-aversion
      can be reversed to risk-seeking within the gain situation, and vice versa within
      the loss situation, by changing the probabilities and the payoffs associated with
      the probabilities. It was suggested that the results of both experiments can be
      understood by a concept of Gestalt organization and dynamic processes in decision
      making. 

PMID- 24897003
TI  - Topographic analysis of the rat's bar behaviour in the Skinner box.
AB  - We analysed precisely, with video tapes, the behaviour of 38 Wistar rats
      submitted to a continuous reinforcement in a Skinner box. Animals displayed 14
      different behavioural patterns close to the bar. We found that the increasing
      frequency of the bar press, generally considered as a unitary response was, in
      fact, due to summation of the development of several different behaviour
      frequencies. A CAH analysis led to the distinction of 5 behavioural categories.
      The frequency of each category of behavioural patterns varied throughout learning
      in respect with the number of sessions before criterion. So, learning in the
      Skinner box would result from an association of the reinforcers with the
      successive units of behaviour exhibited by animals at the bar whose sequential
      organization and nature change according to acquisition rapidity. 

PMID- 24897004
TI  - Chiral electronic transitions in fluorescent silver clusters stabilized by DNA.
AB  - Fluorescent, DNA-stabilized silver clusters are receiving much attention for
      sequence-selected colors and high quantum yields. However, limited knowledge of
      cluster structure is constraining further development of these "AgN-DNA"
      nanomaterials. We report the structurally sensitive, chiroptical activity of four
      pure AgN-DNA with wide ranging colors. Ubiquitous features in circular dichroism
      (CD) spectra include a positive dichroic peak overlying the lowest energy
      absorbance peak and highly anisotropic, negative dichroic peaks at energies well
      below DNA transitions. Quantum chemical calculations for bare chains of silver
      atoms with nonplanar curvature also exhibit these striking features, indicating
      electron flow along a chiral, filamentary metallic path as the origin for low
      energy AgN-DNA transitions. Relative to the bare DNA, marked UV changes in CD
      spectra of AgN-DNA and silver cation-DNA solutions indicate that ionic silver
      content constrains nucleobase conformation. Changes in solvent composition alone
      can reorganize cluster structure, reconfiguring chiroptical properties and
      fluorescence. 

PMID- 24897005
TI  - PAX immunoreactivity in poorly differentiated small round cell tumors of
      childhood.
AB  - Paired box (PAX) gene antibodies have made it into the mainstream of tumor
      diagnosis in the recent years. We report the immunoreactivity expression patterns
      of three PAX genes (PAX2, PAX5 and PAX8) in poorly differentiated small round
      cell tumors of childhood for possible useful diagnostic applications. We
      collected and analyzed 123 cases of poorly differentiated small round cell tumors
      of childhood for their PAX immunoexpression patterns. The results indicated that
      PAX2 was strongly positive in all alveolar rhabdomyosarcomas and in two-thirds of
      the kidney clear cell sarcomas, and displayed variable expression in one-half of
      the embryonal rhabdomyosarcomas. PAX8 immunoexpression was noticed in five and
      three cases of alveolar rhabdomyosarcomas and embryonal rhabdomyosarcomas,
      respectively. About one-third of malignant rhabdoid tumors were PAX2-positive and
      PAX8-positive. All of the Ewing sarcoma and neuroblastoma cases stained negative
      with all three PAX stains. 

PMID- 24897006
TI  - Experimental and theoretical analysis of transport properties of core-shell wire
      light emitting diodes probed by electron beam induced current microscopy.
AB  - We report a systematic experimental and theoretical investigation of core-shell
      InGaN/GaN single wire light-emitting diodes (LEDs) using electron beam induced
      current (EBIC) microscopy. The wires were grown by catalyst-free MOVPE and
      processed into single wire LEDs using electron beam lithography on dispersed
      wires. The influence of the acceleration voltage and of the applied bias on the
      EBIC maps was investigated. We show that the EBIC maps provide information both
      on the minority carrier effects (i.e. on the local p-n junction collection
      efficiency) and on the majority carrier effects (i.e. the transport efficiency
      from the excited region toward the contacts). Because of a finite core and shell
      resistance a non-negligible current redistribution into the p-n junction takes
      place during the majority carrier transport. A theoretical model for transport in
      a core-shell wire is developed, allowing to explain the dependence of the EBIC
      profiles on the experimental parameters (the electron beam acceleration voltage
      and the bias applied on the device) and on the structural parameters of the wire
      (core and shell resistance, shunt resistance, etc). Comparison between simulated
      and experimental profiles provides valuable information concerning the structure
      inhomogeneities and gives insight into the wire electrical parameters. 

PMID- 24897007
TI  - Nervus intermedius meningioma.
AB  - OBJECTIVE: To report a case of meningioma arising from the nervus intermedius.
      METHODS: This paper comprises a case report, literature review, and discussion
      regarding the presentation of a nervus intermedius meningioma, comparing and
      contrasting this to other relevant neoplasms of the internal auditory canal and
      cerebellopontine angle. RESULTS: Tumours of the cerebellopontine angle include
      vestibular schwannomas, facial schwannomas and, more rarely, nervus intermedius
      schwannomas. The nervus intermedius is a division of the facial nerve at the
      cerebellopontine angle, with parasympathetic and afferent somatic components. Our
      patient presented with progressive hearing loss. An ipsilateral internal auditory
      canal mass at the fundus, as indicated by magnetic resonance imaging and
      electroneuronography, was suggestive of vestibular schwannoma. Intra-operative
      dissection revealed a nervus intermedius tumour. Histological evaluation
      indicated a meningioma rather than a schwannoma. CONCLUSION: This is the first
      reported case of meningioma involving the nervus intermedius. The implications
      this pathology may have on surgical approach, facial nerve outcomes, and the need
      for improved pre-operative imaging and intra-operative monitoring are discussed.
      A review of the current literature on nervus intermedius tumour is provided.

PMID- 24897008
TI  - Visual recovery after surgical decompression of an occipital intraventricular
      cyst.
AB  - : A 62-year-old woman presented with a chronic left homonymous visual field
      defect because of a right occipital cyst. Serial visual field examination
      documented stable visual fields for 12 months, after which there was worsening of
      visual fields associated with enlargement of the cyst. Surgical decompression of
      the occipital cyst resulted in marked improvement of the visual field defect over
      9 months. This case demonstrates that surgical decompression of cystic lesions
      adjacent to posterior visual pathways can result in recovery of chronic visual
      field loss. 

PMID- 24897009
TI  - Optochiasmatic and peripheral neuropathy due to ethambutol overtreatment.
AB  - Ethambutol is known to cause optic neuropathy and, more rarely, axonal
      polyneuropathy. We characterize the clinical, neurophysiological, and
      neuroimaging findings in a 72-year-old man who developed visual loss and
      paresthesias after 11 weeks of exposure to a supratherapeutic dose of ethambutol.
      This case demonstrates the selective vulnerability of the anterior visual
      pathways and peripheral nerves to ethambutol toxicity.

PMID- 24897010
TI  - Vitreous seeding from a large optic disc melanocytoma.
AB  - We report the case of a 17 year-old man with a large optic disc melanocytoma that
      underwent spontaneous rupture and seeding of the vitreous with pigmented cells.
      Potential pathogenic mechanisms and visual prognosis of this rare event are
      discussed.

PMID- 24897011
TI  - Dietary intakes in the nutritional management of gestational diabetes mellitus.
AB  - PURPOSE: Changes were examined in energy intakes and percentage of energy from
      macronutrients in response to nutritional intervention in women with gestational
      diabetes mellitus (GDM). METHODS: The study included 17 women with GDM and 27
      women with normal glucose tolerance (controls). Women with GDM were followed by a
      multidisciplinary team; they received dietary counselling by a registered
      dietitian, and were prescribed diets with 40% to 45% energy from carbohydrate
      (CHO), 20% to 25% from protein, and 30% to 35% from fat. Dietary intakes were
      assessed with food frequency questionnaires before the intervention (26.9 +/- 3.8
      weeks) and after the intervention (32.6 +/- 0.6 weeks). RESULTS: After the
      intervention, women with GDM reduced their total energy intake to reach lower
      values than did controls (P value for time-group interaction =0.05). A
      concomitant reduction in total CHO and glucose intakes in women with GDM led to
      significantly lower values compared with intakes in controls (P values for time
      group interaction =0.001 for all). The post-intervention rate of weight gain in
      women with GDM was within the Institute of Medicine (IOM)-recommended values,
      while the post-intervention rate of weight gain in controls was above IOM
      recommended values (0.30 +/- 0.27 versus 0.61 +/- 0.50 kg/week, P<=0.05).
      CONCLUSIONS: These results suggest that this multidisciplinary medical and
      nutritional intervention was effective in the achievement of prescribed
      macronutrient distribution and controlling gestational weight gain in Canadian
      women with GDM.

PMID- 24897012
TI  - The Complete Health Improvement Program (CHIP) and reduction of chronic disease
      risk factors in Canada.
AB  - PURPOSE: The short-term effectiveness of the nutrition-centred Complete Health
      Improvement Program (CHIP) lifestyle intervention for improving selected chronic
      disease risk factors was examined in the Canadian setting. METHODS: A total of
      1003 people (aged 56.3 +/- 12.1 years, 68% female) were self-selected to
      participate in one of 27 CHIP interventions hosted in community settings by
      Seventh-day Adventist churches throughout Canada, between 2005 and 2011. The
      program centred on the promotion of a whole-food, plant-based eating pattern, and
      daily physical activity was also encouraged. Biometric measures, including body
      mass index (BMI), blood pressure (BP), blood lipid profile, and fasting blood
      sugar (FBS), were determined at program entry and 30 days into the intervention.
      RESULTS: Over 30 days, significant overall reductions (P<0.001) were recorded in
      the participants' BMI (-3.1%), systolic BP (-7.3%), diastolic BP (-4.3%), total
      cholesterol ([TC] -11.3%), low-density lipoprotein cholesterol ([LDL-C] -12.9%),
      triglycerides ([TG] -8.2%), and FBS (-7.0%). Participants with the highest
      classifications of TC, LDL-C, TG, and FBS at program entry experienced
      approximately 20% reductions in these measures in 30 days. CONCLUSIONS: The CHIP
      intervention, which centres on a whole-food, plant-based eating pattern, can lead
      to rapid and meaningful reductions in chronic disease risk factors in the
      Canadian context.

PMID- 24897013
TI  - Registered dietitians' roles in decision-making processes for PEG placement in
      the elderly.
AB  - PURPOSE: The role of registered dietitians (RDs) in decision-making for
      percutaneous endoscopic gastrostomy (PEG) placement was explored. The ethical
      climate in their workplace and the relationship between decision-making and the
      ethical climate were examined. METHODS: The survey included 67 RDs in complex
      continuing care and long-term care settings in Ontario. Descriptive statistics
      were used to describe roles, ethical climate, and professional characteristics.
      Pearson's and nonparametric correlations were used to examine relationships
      between roles, ethical climate, and professional characteristics. RESULTS: Among
      the respondents, 97% thought RDs had a role in decision-making processes. The
      majority of RDs were usually or always involved in two roles: identifying
      relevant nutrition issues (91.2%) and discussing feeding options and alternatives
      (80.7%). Dietitians' roles in decision-making processes were more extensive when
      their relationship with physicians was positive (r=0.321, P=0.016), they had
      adequate knowledge (r=0.465, P<0.001) and adequate skills (r=0.520, P<0.001), and
      they were more satisfied with their role (r=0.554, P<0.001). CONCLUSIONS:
      Registered dietitians performed a variety of roles in decision-making processes
      concerning PEG placement in the elderly. A positive working relationship with
      physicians, knowledge, skills, and role satisfaction significantly increase RDs'
      involvement with patients and families.

PMID- 24897014
TI  - Nutritional risk in community-dwelling older men: the Manitoba follow-up study.
AB  - PURPOSE: The role of nutrition in older men's health and successful aging has
      been inadequately studied. We examined the relationships among nutritional risk,
      self-rated health, and successful aging in community-dwelling Canadian older men.
      METHODS: The surviving cohort of the Manitoba Follow-up Study (n=690, mean age =
      86.8 years) were sent a self-administered nutrition survey in December 2007. The
      survey consisted of the Seniors in the Community: Risk Evaluation for Eating and
      Nutrition, version II (SCREEN II), a validated tool for assessing nutritional
      risk of cognitively intact community-living older adults, and questions about
      successful aging and health. RESULTS: Of the 553 surveys returned (80% response),
      522 with complete SCREEN II data were included in the analysis. Forty-four
      percent of respondents were at high nutritional risk, 24% were at moderate risk,
      and 32% were at low risk. Significant relationships were found between
      nutritional risk and self-rated health (P<0.0001) and successful aging (P=0.008),
      with greater nutritional risk associated with lower self-ratings of health and
      successful aging. Higher use of prescription medication was related to greater
      nutritional risk (P=0.004). CONCLUSIONS: Nutritional screening programs for
      community-dwelling older men are warranted as two-thirds of the study
      participants were at nutritional risk. Identifying older men at nutritional risk
      is a critical step in the process of nutritional assessment, and subsequent
      nutrition interventions and follow-up are required to prevent further health
      decline.

PMID- 24897015
TI  - Crafting meaning: arts-informed dietetics education.
AB  - PURPOSE: University nutrition students' experiences of participation in an arts
      module as part of a senior nutrition course were explored to gain an
      understanding of the relationship of art to dietetics practice. METHODS: The
      module comprised discussions, readings, and presentations from dietitian artists,
      along with three assignments: the production of art, an artist statement, and a
      reflection paper. The art production depicting an aspect of body image was
      presented to the class and optionally at a body image conference. An exploratory,
      qualitative methodology informed by Schon's reflective practice framework was
      employed. Three surveys administered at various times during the arts module were
      used to collect students' reflections and were thematically analyzed. RESULTS:
      Three themes emerged: hesitance to acceptance, emotion and connection, and
      relationship with dietetics. The education process facilitated a transformation
      among students, noted as changes in knowledge, perceptions, and attitudes over
      the course of the module. CONCLUSIONS: The arts provide an alternative platform
      for an exploration of self and others, for improving practice, and for an
      examination of novel ways for doing so. Reflection as an education component
      enables students to contemplate relationships, knowledge, emotions, and practice
      as interrelated and evolving entities.

PMID- 24897016
TI  - A sustainable dietetics bridging program: development and implementation in
      Atlantic Canada.
AB  - A provincial focus on immigration and improved foreign credential recognition has
      led to an investigation of best practices and subsequent recommendations for the
      development and implementation of a sustainable university-based bridging program
      for internationally educated dietitians in Atlantic Canada. Data were collected
      from various sources and used to inform program decisions and direction. An
      advisory framework was established through a core group representing dietetics
      education and regulation and internationalization. Subsequently, a key
      stakeholder group was formed. As a result of this collaboration and research, a
      dietetics bridging framework was developed and a program pilot tested. Lessons
      learned may inform similar endeavours and highlight the importance of
      collaborative leadership and collaboration among multiple stakeholders, and of
      creatively addressing program sustainability issues while keeping learners
      (internationally educated dietitians) at the centre. 

PMID- 24897017
TI  - Enhanced dietetics education through collaboration: a study to identify
      opportunities.
AB  - With the aim of enhancing dietetics education in Nova Scotia, key stakeholders
      were engaged in identifying current practice issues along with opportunities for
      collaboration to address them. A survey containing five open-ended questions was
      distributed by email to a purposive sample of 24 participants affiliated with
      three universities with dietetics programs. Participants fell into five
      categories: internship coordinators, dietetics educators, recent internship
      graduates, current interns, and prospective interns. The response rate was 58%.
      Data were thematically analyzed through a process of constant comparison. Primary
      themes emerged, which reflected survey participants' concerns about three current
      practice issues: province-wide standards, internship placement availability, and
      the overall educational experience. Additional comments suggested that overall
      dietetic educational experiences could be improved if relevant clinical
      experiences were offered and preceptor workloads were accommodated. The creation
      of province-wide standards for assessing interns' level of competency was
      perceived to offer multiple benefits, including decreased preceptor workloads.
      Participants believed that collaborative actions might increase internship
      placements and improve the overall dietetic internship experience for interns and
      preceptors. 

PMID- 24897018
TI  - Experiences of people of Acadian descent receiving hemodialysis in southwest Nova
      Scotia.
AB  - We conducted a group interview with five hemodialysis patients of Acadian
      descent. Our purpose was to learn about their intakes of Acadian foods so we
      could tailor our advice for other Acadian patients receiving hemodialysis. This
      approach builds on evidence that addressing cultural aspects of food choice and
      aligning dietary recommendations with usual intakes create optimal conditions for
      diet adherence while preserving personal habits and heritage. In this study, "the
      Acadian diet" held multiple meanings for different participants, participants
      varied in their intakes of traditional Acadian foods, intakes of traditional
      Acadian foods were decreasing in younger generations, and the desire to preserve
      kidney function had priority over eating much-loved traditional foods. These
      findings support the practices of individualized nutritional and dialysis care
      and discourage generalized nutrition messages based on assumptions of homogeneity
      of all people within a cultural group. 

PMID- 24897019
TI  - Picture this: a photovoice study of international students' food experience in
      Canada.
AB  - PURPOSE: International student enrolment in Canadian universities is increasing.
      As international university students acculturate, they experience a culture shock
      in which food plays a major role. International university students' Canadian
      food experiences therefore were explored. METHODS: A Photovoice methodology was
      used with 15 international undergraduate and graduate university students, who
      were recruited to take pictures of their food experiences. They also participated
      in two focus group discussions that included an analysis of their photos.
      RESULTS: Seven themes related to the significance of food in acculturation were
      revealed: the paradox of Canadian convenience, the equation of traditional foods
      with health, traditional food quality and accessibility, support networks, food
      consumption for comfort, ethnic restaurants, and the exploration of non
      traditional foods. Maintaining cultural identity with traditional foods was an
      overarching theme related to acculturation. CONCLUSIONS: International students
      acculturating to Canada have emotional and physical needs, which can be met
      through food. Opportunities exist to improve their acculturation experiences.
      Canadian universities can incorporate food acculturation strategies into campus
      events and menus. Nutrition professionals on campus can facilitate a positive
      food environment and nurture culture identity formation.

PMID- 24897021
TI  - Qualitative analysis of the helical electronic energy of inherently chiral
      calix[4]arenes: an approach to effectively assign their absolute configuration.
AB  - For all microhelices on aromatic rings of inherently chiral calix[4]arene, an
      expression was derived from one approximation and one hypothesis on the basis of
      the electron-on-a-helix model of Tinoco and Woody as follows: 1/E = MU(H -
      KDeltaalpha2), where MU = 1 for the right-handed microhelix and MU = -1 for the
      left-handed microhelix; and H and K are constant and greater than zero. The
      expression correlates microhelical electronic energy (E) with the atom
      polarizability difference (Deltaalpha) on both microhelix ends, which intuitively
      and clearly shows the impact of helical substituent polarizability on helical
      electronic energy. The case analysis almost entirely proves that the qualitative
      analysis of the helical electronic energy of inherently chiral calix[4]arenes
      with the expression is scientific and can be used to effectively assign their
      absolute configuration.

PMID- 24897020
TI  - Genetic variants in human leukocyte antigen-DP influence both hepatitis C virus
      persistence and hepatitis C virus F protein generation in the Chinese Han
      population.
AB  - Chronic hepatitis C is a serious liver disease that often results in cirrhosis or
      hepatocellular carcinoma. The aim of this study was to assess the association of
      human leukocyte antigen-DP (HLA-DP) variants with risk of chronic hepatitis C
      virus (HCV) or anti-F antibody generation. We selected two single nucleotide
      polymorphisms (SNPs) in a region including HLA-DPA1 (rs3077) and HLA-DPB1
      (rs9277534) and genotyped SNPs in 702 cases and 342 healthy controls from the
      Chinese population using TaqMan SNP genotyping assay. Moreover, the exon 2 of the
      HLA-DPA1 and HLA-DPB1 genes were amplified and determined by sequencing-based
      typing (SBT). The results showed that rs3077 significantly increased the risk of
      chronic HCV infection in additive models and dominant models (odds ratio (OR) =
      1.32 and 1.53). The rs3077 also contributed to decrease the risk of anti-F
      antibody generation in additive models and dominant models (OR = 0.46 and 0.56).
      Subsequent analyses revealed the risk haplotypes (DPA1*0103-DPB1*0501 and
      DPA1*0103-DPB1*0201) and protective haplotypes (DPA1*0202-DPB1*0501 and DPA1*0202
      DPB1*0202) to chronic HCV infection. Moreover, we also found that the haplotype
      of DPA1*0103-DPB1*0201 and DPA1*0202-DPB1*0202 were associated with the anti-F
      antibody generation. Our findings show that genetic variants in HLA-DP gene are
      associated with chronic HCV infection and anti-F antibody generation. 

PMID- 24897022
TI  - Ginsenoside Rd attenuates mitochondrial permeability transition and cytochrome C
      release in isolated spinal cord mitochondria: involvement of kinase-mediated
      pathways.
AB  - Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has
      multifunctional activity via different mechanisms and neuroprotective effects
      that are exerted probably via its antioxidant or free radical scavenger action.
      However, the effects of Rd on spinal cord mitochondrial dysfunction and
      underlying mechanisms are still obscure. In this study, we sought to investigate
      the in vitro effects of Rd on mitochondrial integrity and redox balance in
      isolated spinal cord mitochondria. We verified that Ca2+ dissipated the membrane
      potential, provoked mitochondrial swelling and decreased NAD(P)H matrix content,
      which were all attenuated by Rd pretreatment in a dose-dependent manner. In
      contrast, Rd was not able to inhibit Ca2+ induced mitochondrial hydrogen peroxide
      generation. The results of Western blot showed that Rd significantly increased
      the expression of p-Akt and p-ERK, but had no effects on phosphorylation of PKC
      and p38. In addition, Rd treatment significantly attenuated Ca2+ induced
      cytochrome c release, which was partly reversed by antagonists of Akt and ERK,
      but not p-38 inhibitor. The effects of bisindolylmaleimide, a PKC inhibitor, on
      Rd-induced inhibition of cytochrome c release seem to be at the level of its own
      detrimental activity on mitochondrial function. Furthermore, we also found that
      pretreatment with Rd in vivo (10 and 50 mg/kg) protected spinal cord mitochondria
      against Ca2+ induced mitochondrial membrane potential dissipation and cytochrome
      c release. It is concluded that Rd regulate mitochondrial permeability transition
      pore formation and cytochrome c release through protein kinases dependent
      mechanism involving activation of intramitochondrial Akt and ERK pathways. 

PMID- 24897023
TI  - SPECT and PET serve as molecular imaging techniques and in vivo biomarkers for
      brain metastases.
AB  - Nuclear medicine techniques (single photon emission computerized tomography,
      SPECT, and positron emission tomography, PET) represent molecular imaging tools,
      able to provide in vivo biomarkers of different diseases. To investigate brain
      tumours and metastases many different radiopharmaceuticals imaged by SPECT and
      PET can be used. In this review the main and most promising radiopharmaceuticals
      available to detect brain metastases are reported. Furthermore the diagnostic
      contribution of the combination of SPECT and PET data with radiological findings
      (magnetic resonance imaging, MRI) is discussed. 

PMID- 24897025
TI  - The influence of ecological and conventional plant production systems on soil
      microbial quality under hops (Humulus lupulus).
AB  - The knowledge about microorganisms-activity and diversity under hop production is
      still limited. We assumed that, different systems of hop production (within the
      same soil and climatic conditions) significantly influence on the composition of
      soil microbial populations and its functional activity (metabolic potential).
      Therefore, we compared a set of soil microbial properties in the field experiment
      of two hop production systems (a) ecological based on the use of probiotic
      preparations and organic fertilization (b) conventional-with the use of chemical
      pesticides and mineral fertilizers. Soil analyses included following microbial
      properties: The total number microorganisms, a bunch of soil enzyme activities,
      the catabolic potential was also assessed following Biolog EcoPlates(r).
      Moreover, the abundance of ammonia-oxidizing archaea (AOA) was characterized by
      terminal restriction fragment length polymorphism analysis (T-RFLP) of PCR
      ammonia monooxygenase alpha-subunit (amoA) gene products. Conventional and
      ecological systems of hop production were able to affect soil microbial state in
      different seasonal manner. Favorable effect on soil microbial activity met under
      ecological, was more probably due to livestock-based manure and fermented plant
      extracts application. No negative influence on conventional hopyard soil was
      revealed. Both type of production fulfilled fertilizing demands. Under ecological
      production it was due to livestock-based manure fertilizers and fermented plant
      extracts application. 

PMID- 24897024
TI  - High cytoplasmic expression of Kruppel-like factor 4 is an independent prognostic
      factor of better survival in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      mortality in the world. Hepatocarcinogenesis is complex, with an extraordinary
      molecular heterogeneity. Kruppel-like factor 4 (KLF4) plays an important role in
      cell proliferation and differentiation, and it can function as a tumor suppressor
      or an oncoprotein, depending on tissue type. The role of KLF4 in HCC remains
      controversial. The aim of this study was to explore the clinical significance of
      KLF4 expression in HCC. The study included 205 patients with surgical resection.
      We performed immunostaining for KLF4 and Ki-67 to investigate the correlations of
      the clinicopathological parameters of HCC and to examine the proliferative index.
      KLF4 staining was observed in the cytoplasm of non-tumorous hepatocytes and tumor
      cells. We subdivided the immunohistological staining results for KLF4 into low
      expression (Staining 0 and 1+) and high expression (Staining 2+ and 3+)
      subgroups. The expression of KLF4 was significantly correlated with tumor
      differentiation (p = 0.001). The Ki-67 proliferative index was significantly
      lower in well-differentiated HCCs (0.781% +/- 1.02% vs. 2.16% +/- 3.14%, p =
      0.012), but not significantly different between low-KLF4 expression and high-KLF4
      expression (1.87% +/- 2.93% vs. 2.51% +/- 3.28%, p = 0.32). Kaplan-Meier analysis
      showed that a high expression of KLF4 was significantly correlated with a longer
      disease-specific survival (p = 0.019). Univariate and multivariate analyses
      showed that high KLF4 expression was an independent predictor of a better disease
      specific survival (p = 0.017; hazard ratio = 0.398; 95% confidence interval: 0.19
      0.85). High cytoplasmic expression of KLF4 was associated with better disease
      specific survival and was an independently favorable prognostic factor in
      hepatocellular carcinoma. These promising results suggest that KLF4 may play an
      anti-oncogenic role in hepatocarcinogenesis. 

PMID- 24897027
TI  - Transciliary supraorbital approach (eyebrow approach) for resection of
      retrochiasmatic craniopharyngiomas: an alternative approach, case series, and
      literature review.
AB  - INTRODUCTION: Craniopharyngiomas are known for an irregular growth pattern and
      extension into the retrochiasmatic space with adherence to adjacent structures.
      We describe the use of the transciliary supraorbital approach (eyebrow approach)
      for resection of craniopharyngiomas with retrochiasmatic extension. METHODS: Our
      clinical database was reviewed to identify operative cases of craniopharyngiomas
      between July 1998 and January 2011. Only patients who had retrochiasmatic
      extension and underwent an eyebrow approach were included in this analysis.
      Endoscopy was used to aid surgical resection at the discretion of the surgeon.
      Six patients were identified (three from a retrospective review and three during
      the course of prospective follow-up evaluation). RESULTS: The group included
      three men and three women (mean age: 41.2 years; range: 28-57 years). All
      patients had visual and hormonal deficits at presentation. Complete resection was
      achieved in four patients. Endoscopic assistance was used in three patients.
      Opening of the frontal sinus occurred in two cases during surgery; an additional
      surgical procedure was required for repair of a cerebrospinal fluid leak in one
      of these cases. The duration of clinical follow-up ranged from 18 to 97 months.
      All patients had excellent cosmetic results, visual improvement to a serviceable
      level, and a Karnofsky performance scale score >= 80. CONCLUSIONS: The eyebrow
      approach is safe for resection of craniopharyngiomas with retrochiasmatic
      extension. This approach offers a reasonable surgical corridor for resection of
      the retrochiasmatic tumor component and can be enhanced using endoscopic
      assistance.

PMID- 24897031
TI  - Report on ISN Forefronts, Florence, Italy, 12-15 September 2013: Stem cells and
      kidney regeneration.
AB  - In recent years it has become clear that most organs and tissues, including
      kidney, contain resident stem/progenitor cells. Stem cells are undifferentiated,
      long-lived cells that are unique in their ability to produce differentiated
      daughter cells and to retain their stem cell identity by self-renewal. A primary
      goal of this meeting was to review the current understanding of kidney stem cells
      and mechanisms of kidney regeneration in both lower vertebrates and mammals.
      Presenters covered a broad range of topics including stem cell quiescence,
      epigenetics, transcriptional control circuits, dedifferentiation, pluripotent
      stem cells, renal progenitors, and novel imaging approaches in kidney
      regeneration. By the end of this highly interactive conference it was clear we
      are entering into very exciting times for regenerative medicine and the kidney. 

PMID- 24897032
TI  - Morbidity and treatment in patients with atrial fibrillation and chronic kidney
      disease.
AB  - Chronic kidney disease (CKD) is associated with increased cardiovascular
      morbidity and mortality but there are few studies available about atrial
      fibrillation, the most frequent arrhythmia in CKD, and the applied treatment.
      Based on the prospective German Competence NETwork on Atrial Fibrillation, data
      of 3138 patients with atrial fibrillation were analyzed and categorized by their
      estimated glomerular filtration rate (stages 1-3 and 4 plus 5). With advanced
      CKD, significantly more patients suffered from a more severe form of atrial
      fibrillation. Despite significantly higher CHADS2 scores in advanced CKD, oral
      anticoagulation was not prescribed more frequently while antiarrhythmic drugs and
      catheter ablations were used significantly less often, in contrast to more
      pacemaker implantations. However, in multivariate hierarchical logistic
      regression analyses of in-hospital treatments and complications, only hemorrhages
      and pacemaker implantations turned out to be independently and significantly
      associated with higher CKD stages. This nationwide study shows that patients with
      CKD and atrial fibrillation suffer from a markedly higher comorbidity. Thus,
      while CKD patients have received cardioversions, ablations, antiarrhythmic, or
      anticoagulation drugs significantly less often in their history, current
      treatments were not different if adjusted for multiple comorbidities. This might
      indicate an improvement in the often reported therapeutic nihilism in CKD. 

PMID- 24897033
TI  - Development of the circadian clockwork in the kidney.
AB  - The circadian molecular clock is an internal time-keeping system composed of
      centrally synchronized tissue-level pacemakers. Here, we explored the ontogeny of
      the clock machinery in the developing kidney. Pregnant rats were housed at 12-12
      h light-dark cycles. Offsprings were killed at 4-h intervals on embryonic day 20
      and at postnatal weeks 1, 4, and 12. Canonical clock gene (Clock, Bmal1, Rev
      erbalpha, Cry1, Cry2, Per1, Per2) and kidney-specific clock-controlled gene
      (alphaENaC, SGK1, NHE3, AVPR2) expression was profiled by RT-PCR. To investigate
      the role of nutritional cues, the feeding pattern was modified postpartum. Clock,
      Rev-erbalpha, Per2, alphaENaC, SGK1, NHE3, and AVPR2 showed circadian expression
      at the end of intrauterine development. By 1 week, all genes oscillated with a
      distinct acrophase shift toward the time of peak feeding activity. Daily 4-hour
      withdrawal of mothers induced a 12-hour phase shift of Clock and Bmal1
      expression, while disrupting oscillations of the other genes. After weaning,
      oscillation phases shifted back toward the adult pattern, which was fully
      expressed at 12 weeks. Thus, functional circadian molecular clockwork evolves in
      the late fetal and early postnatal kidney. During the nursing period,
      oscillations are entrained by nutritional cues. The coupling of the circadian
      expression of tubular regulators of fluid and electrolyte excretion to the
      feeding-entrained clockwork may be important to maintain homeostasis during this
      critical period. 

PMID- 24897026
TI  - Steatosis and steatohepatitis: complex disorders.
AB  - Non-alcoholic fatty liver disease (NAFLD) which includes steatosis and
      steatohepatitis, in particular non-alcoholic steatohepatitis (NASH), is a rising
      health problem world-wide and should be separated from alcoholic steatohepatitis
      (ASH). NAFLD is regarded as hepatic manifestation of the metabolic syndrome
      (MetSy), being tightly linked to obesity and type 2 diabetes mellitus (T2DM).
      Development of steatosis, liver fibrosis and cirrhosis often progresses towards
      hepatocellular carcinogenesis and frequently results in the indication for liver
      transplantation, underlining the clinical significance of this disease complex.
      Work on different murine models and several human patients studies led to the
      identification of different molecular key players as well as epigenetic factors
      like miRNAs and SNPs, which have a promoting or protecting function in AFLD/ASH
      or NAFLD/NASH. To which extent they might be translated into human biology and
      pathogenesis is still questionable and needs further investigation regarding
      diagnostic parameters, drug development and a better understanding of the genetic
      impact. In this review we give an overview about the currently available
      knowledge and recent findings regarding the development and progression of this
      disease. 

PMID- 24897035
TI  - The HNF1B score is a simple tool to select patients for HNF1B gene analysis.
AB  - HNF1B-related disease is an emerging condition characterized by an autosomal
      dominant inheritance, a 50% rate of de novo mutations, and a highly variable
      phenotype (renal involvement, maturity-onset diabetes of the young type 5,
      pancreatic hypoplasia, and urogenital tract and liver test abnormalities). Given
      the current lack of pathognomonic characteristics and the wide overlap with other
      conditions, a genetic test is the diagnostic gold standard. However, pre-genetic
      screening is mandatory because genetic testing has substantial costs. Our aim was
      to develop a HNF1B score, based on clinical, imaging, and biological variables,
      as a pivotal tool for rational genetic testing. A score was created using a
      weighted combination of the most discriminative characteristics based on the
      frequency and specificity in published series. The HNF1B score is calculated upon
      17 items including antenatal discovery, family history, and organ involvement
      (kidney, pancreas, liver, and genital tract). The performance of the score was
      assessed by a ROC curve analysis in a 433-individual cohort containing 56 HNF1B
      cases. The HNF1B score efficiently and significantly discriminated between
      mutated and nonmutated cases (AUC 0.78). The optimal cutoff threshold for the
      negative predictive value to rule out HNF1B mutations in a suspected individual
      was 8 (sensitivity 98.2%, specificity 41.1%, and negative predictive value over
      99%). Thus, the HNF1B score is a simple and accurate tool to provide a more
      rational approach to select patients for HNF1B screening. 

PMID- 24897034
TI  - Taming the chronic kidney disease epidemic: a global view of surveillance
      efforts.
AB  - Chronic kidney disease is now recognized to be a worldwide problem associated
      with significant morbidity and mortality and there is a steep increase in the
      number of patients reaching end-stage renal disease. In many parts of the world,
      the disease affects younger people without diabetes or hypertension. The costs to
      family and society can be enormous. Early recognition of CKD may help prevent
      disease progression and the subsequent decline in health and longevity.
      Surveillance programs for early CKD detection are beginning to be implemented in
      a few countries. In this article, we will focus on the challenges and successes
      of these programs with the hope that their eventual and widespread use will
      reduce the complications, deaths, disabilities, and economic burdens associated
      with CKD worldwide. 

PMID- 24897036
TI  - A useful scoring system for the prediction and management of delayed graft
      function following kidney transplantation from cadaveric donors.
AB  - Delayed graft function (DGF) is a common complication in kidney transplantation
      and is known to be correlated with short- and long-term graft outcomes. Here we
      explored the possibility of developing a simple tool that could predict with good
      confidence the occurrence of DGF and could be helpful in current clinical
      practice. We built a score, tentatively called DGFS, from a French multicenter
      and prospective cohort of 1844 adult recipients of deceased donor kidneys
      collected since 2007, and computerized in the Donnees Informatisees et VAlidees
      en Transplantation databank. Only five explicative variables (cold ischemia time,
      donor age, donor serum creatinine, recipient body mass index, and induction
      therapy) contributed significantly to the DGF prediction. These were associated
      with a good predictive capacity (area under the ROC curve at 0.73). The DGFS
      calculation is facilitated by an application available on smartphones, tablets,
      or computers at www.divat.fr/en/online-calculators/dgfs. The DGFS should allow
      the simple classification of patients according to their DGF risk at the time of
      transplantation, and thus allow tailored-specific management or therapeutic
      strategies. 

PMID- 24897038
TI  - Phaeochromocytoma and Acromegaly: a unifying diagnosis.
AB  - A 52-year-old lady was referred after a 5 cm left adrenal mass was detected on
      computed tomography (CT) scanning. She was asymptomatic although was noted to
      have acromegalic facies. Blood pressure (BP) was normal but plasma
      normetanephrines were raised to 2.81 mmol/l (<1.09) and urinary normetadrenaline
      excretion 5.3 MUmol/24 h (0-4.3). Adrenal biochemistry screen was otherwise
      normal. Metaiodobenzylguanidine (MIBG) scan demonstrated uptake in the adrenal
      lesion. Growth hormone (GH) nadir on oral glucose tolerance test (OGTT) was 2.2
      ng/ml with an elevated IGF1 level of 435 ng/ml (72-215), confirming acromegaly
      biochemically. The remainder of the pituitary screen was normal. A magnetic
      resonance imaging (MRI) scan of the pituitary revealed an enlarged pituitary
      gland with a microadenoma/cyst of 2-3 mm in diameter. Alpha blockade was achieved
      with a titrated dose of phenoxybenzamine before a successful laparoscopic hand
      assisted left adrenalectomy. Postoperative biochemical testing revealed a normal
      plasma normetanephrine level of 0.6 nmol/l (<1.09) and a metanephrine level of
      0.35 nmol/l (<0.46 nmol/l). Nadir on OGTT was normal at 0.07 ng/ml with an IGF1
      level within the reference range at 111 ng/ml (75-215). Histology demonstrated a
      well-circumscribed and encapsulated oval mass with microscopic features typical
      for a phaeochromocytoma. The sections stained strongly positive for GHRH in 20%
      of cells on immunocytochemistry. Genetic analysis showed no pathogenic mutation.
      This is a report of the rare condition of a phaeochromocytoma co-secreting GHRH
      resulting in clinical and biochemical acromegaly. Neuroendocrine tumours can
      stain positive for GHRH without coexisting acromegaly, but the resolution of
      patient symptoms and normalisation of serum GH and IGF1 levels following surgery
      imply that this was functional secretion. Pituitary surgery should be avoided in
      such cases. LEARNING POINTS: Incidental findings on imaging require thorough
      investigation to determine the presence of serious pathology.Acromegaly and
      phaeochromocytoma are rarely coincident in the same patient. If this occurs, co
      secretion of GHRH from the phaeochromocytoma or the presence of underlying
      genetic abnormalities must be considered.Acromegaly is due to ectopic GHRH
      secreting neuroendocrine tumours in <1% of cases, most commonly pancreatic or
      bronchial lesions.Co-secretion of GHRH from a phaeochromocytoma is extremely
      rare.In such cases, the pituitary gland may appear enlarged but pituitary surgery
      should be avoided and surgical treatment of the neuroendocrine tumour attempted.

PMID- 24897037
TI  - Soluble urokinase receptor is a biomarker of cardiovascular disease in chronic
      kidney disease.
AB  - Soluble urokinase-type plasminogen activator receptor (suPAR) accumulates in
      patients with chronic kidney disease (CKD). In various non-CKD populations, suPAR
      has been proposed as a prognostic marker for mortality and cardiovascular
      disease. However, it is not known whether suPAR holds prognostic information in
      patients with mild-to-moderate CKD. In a prospective observational study of 476
      patients with mild-to-moderate kidney disease, we examined multivariate
      associations between suPAR, overall mortality, and cardiovascular events. After a
      mean follow-up of 57 months, 52 patients died and 76 patients had at least one
      fatal or nonfatal cardiovascular event. Higher suPAR was directly and
      significantly associated with both overall mortality (univariate hazard ratio
      5.35) and cardiovascular events (univariate hazard ratio 5.06). In multivariate
      analysis, suPAR remained significantly associated with cardiovascular events
      (full model, hazard ratio 3.05). Thus, in patients with mild-to-moderate CKD,
      suPAR concentrations show a clear, direct, and graded association with a higher
      risk for new-onset cardiovascular disease. 

PMID- 24897041
TI  - HIV/AIDS knowledge among men who have sex with men: applying the item response
      theory.
AB  - OBJECTIVE: To evaluate the level of HIV/AIDS knowledge among men who have sex
      with men in Brazil using the latent trait model estimated by Item Response
      Theory. METHODS: Multicenter, cross-sectional study, carried out in ten Brazilian
      cities between 2008 and 2009. Adult men who have sex with men were recruited (n =
      3,746) through Respondent Driven Sampling. HIV/AIDS knowledge was ascertained
      through ten statements by face-to-face interview and latent scores were obtained
      through two-parameter logistic modeling (difficulty and discrimination) using
      Item Response Theory. Differential item functioning was used to examine each item
      characteristic curve by age and schooling. RESULTS: Overall, the HIV/AIDS
      knowledge scores using Item Response Theory did not exceed 6.0 (scale 0-10), with
      mean and median values of 5.0 (SD = 0.9) and 5.3, respectively, with 40.7% of the
      sample with knowledge levels below the average. Some beliefs still exist in this
      population regarding the transmission of the virus by insect bites, by using
      public restrooms, and by sharing utensils during meals. With regard to the
      difficulty and discrimination parameters, eight items were located below the mean
      of the scale and were considered very easy, and four items presented very low
      discrimination parameter (< 0.34). The absence of difficult items contributed to
      the inaccuracy of the measurement of knowledge among those with median level and
      above. CONCLUSIONS: Item Response Theory analysis, which focuses on the
      individual properties of each item, allows measures to be obtained that do not
      vary or depend on the questionnaire, which provides better ascertainment and
      accuracy of knowledge scores. Valid and reliable scales are essential for
      monitoring HIV/AIDS knowledge among the men who have sex with men population over
      time and in different geographic regions, and this psychometric model brings this
      advantage.

PMID- 24897042
TI  - Depressive symptoms in institutionalized older adults.
AB  - OBJECTIVE: To estimate the prevalence of depressive symptoms among
      institutionalized elderly individuals and to analyze factors associated with this
      condition. METHODS: This was a cross-sectional study involving 462 individuals
      aged 60 or older, residents in long stay institutions in four Brazilian
      municipalities. The dependent variable was assessed using the 15-item Geriatric
      Depression Scale. Poisson's regression was used to evaluate associations with co
      variables. We investigated which variables were most relevant in terms of
      presence of depressive symptoms within the studied context through factor
      analysis. RESULTS: Prevalence of depressive symptoms was 48.7%. The variables
      associated with depressive symptoms were: regular/bad/very bad self-rated health;
      comorbidities; hospitalizations; and lack of friends in the institution. Five
      components accounted for 49.2% of total variance of the sample: functioning,
      social support, sensory deficiency, institutionalization and health conditions.
      In the factor analysis, functionality and social support were the components
      which explained a large part of observed variance. CONCLUSIONS: A high prevalence
      of depressive symptoms, with significant variation in distribution, was observed.
      Such results emphasize the importance of health conditions and functioning for
      institutionalized older individuals developing depression. They also point to the
      importance of providing opportunities for interaction among institutionalized
      individuals.

PMID- 24897040
TI  - Towards a unified theory of health-disease: II. Holopathogenesis.
AB  - This article presents a systematic framework for modeling several classes of
      illness-sickness-disease named as Holopathogenesis. Holopathogenesis is defined
      as processes of over-determination of diseases and related conditions taken as a
      whole, comprising selected facets of the complex object Health. First, a
      conceptual background of Holopathogenesis is presented as a series of significant
      interfaces (biomolecular-immunological, physiopathological-clinical,
      epidemiological-ecosocial). Second, propositions derived from Holopathogenesis
      are introduced in order to allow drawing the disease-illness-sickness complex as
      a hierarchical network of networks. Third, a formalization of intra- and inter
      level correspondences, over-determination processes, effects and links of
      Holopathogenesis models is proposed. Finally, the Holopathogenesis frame is
      evaluated as a comprehensive theoretical pathology taken as a preliminary step
      towards a unified theory of health-disease. 

PMID- 24897043
TI  - The impact of stress on the health of sugar cane cutters.
AB  - OBJECTIVE: Evaluate the impact of stress on sugar cane cutters and the prevalence
      of physical and psychological symptoms before and after harvest. METHODS: We
      studied 114 sugarcane cutters and 109 urban workers in the pre-harvest and 102
      sugar cane cutters and 81 urban workers in the post-harvest period in the city of
      Mendonca, SP, Southeastern Brazil, in 2009. Data analysis was based on the
      frequency and percentage of the assessed symptoms of stress, using the Lipp-ISSL
      test (Symptoms of Stress for Adults). The data were analyzed using descriptive
      statistics. The Fisher Test was used to compare the variable of stress between
      pre- and post-harvest within the sugar cane cutter and urban worker groups. P
      values below 0.05 were considered significant. RESULTS: Stress in sugar cane
      cutters increased after harvesting (34.2% pre-harvest and 46.1% post-harvest); in
      urban workers, stress decreased from 44.0% pre-harvest to 42.0% post-harvest.
      There was prevalence of the phase of resistance to stress for both groups with
      signs more apparent from the near-exhaustion and exhaustion phases for sugar cane
      cutters. After harvest, there was a tendency for the number of sugar cane cutters
      with symptoms of near-exhaustion (6.4%) and exhaustion (10.6%) to increase. After
      harvest there was a trend for the number of sugar cane cutters with physical
      symptoms (pre-harvest = 20.5%, post-harvest = 25.5%) and psychological symptoms
      (pre-harvest = 64.1%; post-harvest = 70.2%) to increase. For both groups,
      predominantly psychological symptoms occurred in both phases (70.2% versus
      64.7%). CONCLUSIONS: The work process of cutting cane can cause stress.
      Individual factors such as cognitive perception of the experience, self-efficacy
      beliefs and expectations of the employee regarding their performance can
      influence the understanding of the reactions in their body in face of the work.

PMID- 24897044
TI  - Elaboration and validation of instrument to assess adherence to hypertension
      treatment.
AB  - OBJECTIVE: To elaborate and validate an instrument of adherence to treatment for
      systemic arterial hypertension, based on Item Response Theory. METHODS: The
      process of developing this instrument involved theoretical, empirical and
      analytical procedures. The theoretical procedures included defining the construct
      of adherence to systemic arterial hypertension treatment, identifying areas
      involved and preparing the instrument. The instrument underwent semantic and
      conceptual analysis by experts. The empirical procedure involved the application
      of the instrument to 1,000 users with systemic arterial hypertension treated at a
      referral center in Fortaleza, CE, Northeastern Brazil, in 2012.. The analytical
      phase validated the instrument through psychometric analysis and statistical
      procedures. The Item Response Theory model used in the analysis was the Samejima
      Gradual Response model. RESULTS: Twelve of the 23 items of the original
      instrument were calibrated and remained in the final version. Cronbach's alpha
      coefficient (alpha) was 0.81. Items related to the use of medication when
      presenting symptoms and the use of fat showed good performance as they were more
      capable of discriminating individuals who adhered to treatment. To ever stop
      taking the medication and the consumption of white meat showed less power of
      discrimination. Items related to physical exercise and routinely following the
      non-pharmacological treatment had most difficulty to respond. The instrument was
      more suitable for measuring low adherence to hypertension treatment than high.
      CONCLUSIONS: The instrument proved to be an adequate tool to assess adherence to
      treatment for systemic arterial hypertension since it manages to differentiate
      individuals with high from those with low adherence. Its use could facilitate the
      identification and verification of compliance to prescribed therapy, besides
      allowing the establishment of goals to be achieved.

PMID- 24897045
TI  - Integrality in cervical cancer care: evaluation of access.
AB  - OBJECTIVE: To evaluate integrity of access to uterine cervical cancer prevention,
      diagnosis and treatment services. METHODS: The tracer condition was analyzed
      using a mixed quantitative and qualitative approach. The quantitative approach
      was based on secondary data from the analysis of cytology and biopsy exams
      performed between 2008 and 2010 on 25 to 59 year-old women in a municipality with
      a large population and with the necessary technological resources. Data were
      obtained from the Health Information System and the Regional Cervical Cancer
      Information System. Statistical analysis was performed using PASW statistic 17.0
      software. The qualitative approach involved semi-structured interviews with
      service managers, health care professionals and users. NVivo 9.0 software was
      used for the content analysis of the primary data. RESULTS: Pap smear coverage
      was low, possible due to insufficient screening and the difficulty of making
      appointments in primary care. The numbers of biopsies conducted are similar to
      those of abnormal cytologies, reflecting easy access to the specialized services.
      There was higher coverage among younger women. More serious diagnoses, for both
      cytologies and biopsies, were more prevalent in older women. CONCLUSIONS:
      Insufficient coverage of cytologies, reported by the interviewees allows us to
      understand access difficulties in primary care, as well as the fragility of
      screening strategies.

PMID- 24897046
TI  - Neighborhood contextual characteristics and leisure-time physical activity: Pro
      Saude Study.
AB  - OBJECTIVE: To estimate the association between neighborhood contextual variables
      and leisure-time physical activity. METHODS: Data were analyzed for 2,674 adults
      from Rio de Janeiro, RJ, Southeastern Brazil, participating in the longitudinal
      study in 1999. Leisure-time physical activity in the two preceding weeks was
      assessed dichotomously. Sex, age, income, education and marital status were
      analyzed as individual variables. Neighborhood contextual characteristics were
      the social development index, the Theil index and the proportion of the area
      occupied by parks, squares and gardens, categorized in quintiles. The unadjusted
      and adjusted odds ratios and 95% confidence intervals were estimated using
      multilevel logistic regression. RESULTS: The prevalence of leisure-time physical
      activity was higher in residents in neighborhoods with higher indices of social
      development (between 32.3% and 53.1%) and a greater proportion of parks, squares
      and gardens (between 35.8% and 53.1%). Regarding the social development index,
      the adjusted odds ratios for physical activity were 1.22 (95%CI 0.93;1.61), 1.44
      (95%CI 1.09;1.89), 1.75 (95%CI 1.31;2.34) and 2.25 (95%CI 1.70;3.00) for
      residents in neighborhoods in the second, third, fourth and fifth quintiles,
      respectively, compared with residents in neighborhoods in the first quintile. The
      odds ratios for the proportion of parks, squares and gardens were 0.90 (95%CI
      0.69;1.19), 1.41 (95%CI 1.04;1.90), 1.63 (95%CI 1.24;2.14) and 1.05 (95%CI
      0.80;1.38) for residents in neighborhoods in the second, third, fourth and fifth
      quintiles. After adjusting for the other variables, only the social development
      index continued to be associated with leisure-time physical activity, with odds
      ratios of 1.41 (95%CI 1.02;1.95); 1.54 (95%CI 1.12;2.12); 1.65 (95%CI 1.14;2.39)
      and 2.13 (95%CI 1.40;3.25) for residents in neighborhoods in the second, third,
      fourth and fifth quintiles. CONCLUSIONS: Leisure-time physical activity was more
      common in residents in neighborhoods with higher social development indices. No
      association was observed between access to leisure areas and income inequality.

PMID- 24897047
TI  - Physical activity in climacteric women: comparison between self-reporting and
      pedometer.
AB  - OBJECTIVE: To compare two methods of assessing physical activity in pre-, peri-
      and postmenopausal women. METHODS: Cross-sectional study nested in a cohort of
      pre-, peri- and postmenopausal women in a city in Southern Brazil. The
      participants completed a questionnaire that included sociodemographic and
      clinical data. Physical activity was assessed using a digital pedometer and the
      International Physical Activity Questionnaire, short version. The participants
      were classified into strata of physical activity according to the instrument
      used. For statistical analysis, the Spearman correlation test, Kappa index,
      concordance coefficient and Bland-Altman plots were used. RESULTS: The
      concordance (k = 0110; p = 0.007) and the correlation (rho = 0.136, p = 0.02)
      between the International Physical Activity Questionnaire, short version, and
      pedometer were weak. In Bland-Altman plots, it was observed that differences
      deviate from zero value whether the physical activity is minimal or more intense.
      Comparing the two methods, the frequency of inactive women is higher when
      assessed by pedometer than by the International Physical Activity Questionnaire-
      short version, and the opposite occurs in active women. CONCLUSIONS: Agreement
      between the methods was weak. Although easy to use, Physical Activity
      Questionnaire--short version overestimates physical activity compared with
      assessment by pedometer.

PMID- 24897048
TI  - Prevalence and factors associated with sedentary behavior in adolescents.
AB  - OBJECTIVE: To analyze the prevalence of sedentary behavior and associated factors
      in adolescents. METHODS: A cross-sectional study with adolescents aged 10 to 17
      years, of both sexes, belonging to a 1994-1999 birth cohort in the city of
      Cuiaba, MT, Central Western Brazil. Data were collected using a questionnaire
      containing sociodemographic, economic, lifestyle and anthropometric variables.
      Sedentary behavior was determined as using television and/or computer/video games
      for a time greater than or equal to 4 hours/day. Associations with sedentary
      behavior were evaluated using body mass index in childhood and adolescence and
      sociodemographic and behavioral variables using hierarchical logistic regression.
      RESULTS: The overall prevalence of sedentary behavior was 58.1%. Of the 1,716
      adolescents evaluated, 50.7% (n = 870) were male. In multivariate analysis, after
      adjustment for confounding factors, the variables that remained associated with
      sedentary behavior were: age (14 and over) (OR = 3.51, 95%CI 2.19;5.60); higher
      socioeconomic class (OR = 3.83, 95%CI 2.10;7.01), higher level of maternal
      education (OR = 1.81, 95%CI 1.09;3.01); living in the country (OR = 0.49, 95%CI
      0.30;0.81); insufficient physical activity (OR = 1.25, 95%CI 1.02;1.53);
      experimentation with alcoholic beverages (OR = 1.34, 95%CI 1.08;1.66) and being
      overweight in adolescence (OR = 1.33, 95%CI 1.06;1.68). CONCLUSIONS: The high
      proportion of adolescents in sedentary activities and the lack of association
      with being overweight in childhood, indicates the need for educational
      initiatives to reduce multiple risk behaviors. Encouraging physical activity in
      young people as a way of reducing sedentary behavior and, consequently, being
      overweight is fundamental.

PMID- 24897049
TI  - The need to improve health care in prisons.
AB  - OBJECTIVE: To analyze physical structure, working conditions of health
      professionals and outline of the procedures established in prisons. METHODS: We
      analyzed 34 provisional detention centers and 69 male and six female prison units
      in the state of Sao Paulo, Southeastern Brazil, in 2009. A self-applied
      instrument was developed to collect quantitative data on the characteristics of
      health care structure, equipment and personnel in prisons. Analysis of variance
      (ANOVA) or equivalent non-parametric tests and Chi-square or Fisher's tests were
      used to compare categorical and continuous variables, respectively, between the
      groups. RESULTS: The main problems were delays in the results of laboratory tests
      and imaging. With respect to the teams, it was observed that a large majority
      were in conditions close to those proposed by the Bipartite Commission 2013 but
      without improvement being reflected in the indicators. With respect to the
      process, more than 60.0% of prisons located in small towns do not have the
      structural conditions to ensure secondary or tertiary health care for the
      continuity of treatment. CONCLUSIONS: This profile of prisons in the country can
      be used for planning and monitoring future actions for the continuous improvement
      of healthcare processes.

PMID- 24897050
TI  - Factors associated to persistence with hormonal therapy in women with breast
      cancer.
AB  - OBJECTIVE: To analyze factors associated with persistence to breast cancer
      hormone therapy in order to contribute to the quality of care improvement.
      METHODS: Retrospective longitudinal study, based on secondary data. A cohort of
      5,861 women with breast cancer registered in different datasets of the Brazilian
      National Cancer Institute and the Brazilian Unified Health System were analyzed.
      All women were treated at this hospital, which provides free medication, and the
      follow-up period was from January 2004 to October 2010. Sociodemographic,
      behavioral, and clinical variables, as well as aspects of lifestyle and health
      care, were considered in the explanation of variations in the persistence to
      hormone therapy, applying the Kaplan-Meier method and the Cox proportional hazard
      model. RESULTS: Overall persistence to hormone therapy was 79.0% at the end of
      the first year, and 31.0% in five years of treatment. The risk of discontinuing
      hormone therapy was higher among women under 35 years old, with more advanced
      disease (stages III and IV), alcohol drinkers, those undergoing chemotherapy, and
      for each additional hospitalization, exam performed, and month between diagnosis
      and beginning of treatment. In the opposite direction, the risk of discontinuity
      was lower among women who had at least finished high school, those with partner,
      with a family history of cancer, those who had undergone breast surgery, and who
      had outpatient visits to a Mastologist, and a Clinical Oncologist. CONCLUSIONS:
      The majority of the women with breast cancer (69.0%) do not persist with hormone
      treatment for the five years recommended, increasing the risk of inadequate
      clinical results. The results show aspects of care that can provide better
      results.

PMID- 24897051
TI  - Trypanosoma cruzi strains from triatomine collected in Bahia and Rio Grande do
      Sul, Brazil.
AB  - OBJECTIVE: Collection of triatomines in domestic, peridomestic and sylvatic
      environments in states of Bahia and Rio Grande do Sul, Northeastern and Southern
      Brazil respectively, and isolation of Trypanosoma cruzi strains. METHODS: First,
      the captured triatomines were identified using insect identification keys, then
      their intestinal content was examined by abdominal compression, and the samples
      containing trypanosomatid forms were inoculated in LIT medium and Swiss mice.
      RESULTS: Six triatomine species were collected in cities in Bahia, namely
      Panstrongylus geniculatus (01), Triatoma melanocephala (11), T. lenti (94), T.
      pseudomaculata (02), T. sherlocki (26) and T. sordida (460), and two in cities in
      Rio Grande do Sul, namely T. circummaculata (11) and T. rubrovaria (115). Out of
      the specimens examined, T. cruzi was isolated from 28 triatomine divided into
      four different species: T. melanocephala (one), T. lenti (one), T. rubrovaria
      (16) and T. sordida (10). Their index of natural infection by T. cruzi was 6.4%.
      CONCLUSIONS: The isolation of T. cruzi strains from triatomines found in domestic
      and peridomestic areas shows the potential risk of transmission of Chagas disease
      in the studied cities. The maintenance of those T. cruzi strains in laboratory is
      intended to promote studies that facilitate the understanding of the parasite
      vector-host relationship.

PMID- 24897052
TI  - Comparison of childbirth care models in public hospitals, Brazil.
AB  - OBJECTIVE: To compare collaborative and traditional childbirth care models.
      METHODS: Cross-sectional study with 655 primiparous women in four public health
      system hospitals in Belo Horizonte, MG, Southeastern Brazil, in 2011 (333 women
      for the collaborative model and 322 for the traditional model, including those
      with induced or premature labor). Data were collected using interviews and
      medical records. The Chi-square test was used to compare the outcomes and
      multivariate logistic regression to determine the association between the model
      and the interventions used. RESULTS: Paid work and schooling showed significant
      differences in distribution between the models. Oxytocin (50.2% collaborative
      model and 65.5% traditional model; p < 0.001), amniotomy (54.3% collaborative
      model and 65.9% traditional model; p = 0.012) and episiotomy (collaborative model
      16.1% and traditional model 85.2%; p < 0.001) were less used in the collaborative
      model with increased application of non-pharmacological pain relief (85.0%
      collaborative model and 78.9% traditional model; p = 0.042). The association
      between the collaborative model and the reduction in the use of oxytocin,
      artificial rupture of membranes and episiotomy remained after adjustment for
      confounding. The care model was not associated with complications in newborns or
      mothers neither with the use of spinal or epidural analgesia. CONCLUSIONS: The
      results suggest that collaborative model may reduce interventions performed in
      labor care with similar perinatal outcomes.

PMID- 24897053
TI  - Reasons for discharge delays in teaching hospitals.
AB  - OBJECTIVE: To analyze the causes of delay in hospital discharge of patients
      admitted to internal medicine wards. METHODS: We reviewed 395 medical records of
      consecutive patients admitted to internal medicine wards of two public teaching
      hospitals: Hospital das Clinicas of the Universidade Federal de Minas Gerais and
      Hospital Odilon Behrens. The Appropriateness Evaluation Protocol was used to
      define the moment at which notes in the medical records indicated hospital stay
      was no longer appropriate and patients could be discharged. The interval between
      this estimated time and actual discharge was defined as the total number of days
      of delay in hospital discharge. An instrument was used to systematically
      categorize reasons for delay in hospital discharge and frequencies were analyzed.
      RESULTS: Delays in discharge occurred in 60.0% of 207 hospital admissions in the
      Hospital das Clinicas and in 58.0% of 188 hospital admissions in the Hospital
      Odilon Behrens. Mean delay per patient was 4.5 days in the former and 4.1 days in
      the latter, corresponding to 23.0% and 28.0% of occupancy rates in each hospital,
      respectively. The main reasons for delay in the two hospitals were, respectively,
      waiting for complementary tests (30.6% versus 34.7%) or for results of performed
      tests to be released (22.4% versus 11.9%) and medical-related accountability
      (36.2% versus 26.1%) which comprised delays in discussing the clinical case and
      in clinical decision making and difficulties in providing specialized
      consultation (20.4% versus 9.1%). CONCLUSIONS: Both hospitals showed a high
      percentage of delay in hospital discharge. The delays were mainly related to
      processes that could be improved by interventions by care teams and managers. The
      impact on mean length of stay and hospital occupancy rates was significant and
      troubling in a scenario of relative shortage of beds and long waiting lists for
      hospital admission.

PMID- 24897054
TI  - Group A beta-hemolytic streptococcal pharyngotonsillitis outbreak.
AB  - The aim was to describe an outbreak of group A beta-hemolytic streptococcal
      pharyngotonsillitis in health care professionals. This is a cross-sectional
      descriptive study of 17 clients who dined at the same table in a restaurant in
      Barcelona in July 2012. The frequency, timing and severity of symptoms were
      analyzed, as were demographic variables and others concerning the food ingested.
      The attack rate was 58.8%. Six of the 10 clients were positive for group A beta
      hemolytic streptococcal. Six of the 13 individuals who handled the food involved
      in the dinner had symptoms. No association was identified with the food consumed.
      There is epidemiological evidence of foodborne group A beta-hemolytic
      streptococcal transmission, but respiratory transmission could not be ruled out. 

PMID- 24897055
TI  - Air pollution and respiratory allergic diseases in schoolchildren.
AB  - Study on the prevalence of allergic respiratory diseases in schoolchildren
      between six and seven years old, associated with indicators of air pollution. A
      questionnaire based on the International Study of Asthma and Allergies in
      Childhood was administered to parents of students from public schools, located in
      urban areas with differing vehicle flows. There was a positive correlation
      between monthly frequency of rhinitis and concentration of pollutants, and
      negative with relative air humidity. Even with levels of air pollutants below
      that allowed by law, the prevalence of asthma, rhinitis and associated symptoms
      tended to be higher in the central region school, where there is heavy vehicular
      traffic. 

PMID- 24897056
TI  - Body image in Brazil: recent advances in the state of knowledge and
      methodological issues.
AB  - OBJECTIVE: To analyze Brazilian literature on body image and the theoretical and
      methodological advances that have been made. METHODS: A detailed review was
      undertaken of the Brazilian literature on body image, selecting published
      articles, dissertations and theses from the SciELO, SCOPUS, LILACS and PubMed
      databases and the CAPES thesis database. Google Scholar was also used. There was
      no start date for the search, which used the following search terms: "body image"
      AND "Brazil" AND "scale(s)"; "body image" AND "Brazil" AND "questionnaire(s)";
      "body image" AND "Brazil" AND "instrument(s)"; "body image" limited to Brazil and
      "body image". RESULTS: The majority of measures available were intended to be
      used in college students, with half of them evaluating
      satisfaction/dissatisfaction with the body. Females and adolescents of both sexes
      were the most studied population. There has been a significant increase in the
      number of available instruments. Nevertheless, numerous published studies have
      used non-validated instruments, with much confusion in the use of the appropriate
      terms (e.g., perception, dissatisfaction, distortion). CONCLUSIONS: Much more is
      needed to understand body image within the Brazilian population, especially in
      terms of evaluating different age groups and diversifying the
      components/dimensions assessed. However, interest in this theme is increasing,
      and important steps have been taken in a short space of time.

PMID- 24897057
TI  - Proposal for a telehealth concept in the translational research model.
AB  - OBJECTIVE: To review the conceptual relationship between telehealth and
      translational research. METHODS: Bibliographical search on telehealth was
      conducted in the Scopus, Cochrane BVS, LILACS and MEDLINE databases to find
      experiences of telehealth in conjunction with discussion of translational
      research in health. The search retrieved eight studies based on analysis of
      models of the five stages of translational research and the multiple strands of
      public health policy in the context of telehealth in Brazil. The models were
      applied to telehealth activities concerning the Network of Human Milk Banks, in
      the Telemedicine University Network. RESULTS: The translational research cycle of
      human milk collected, stored and distributed presents several integrated
      telehealth initiatives, such as video conferencing, and software and portals for
      synthesizing knowledge, composing elements of an information ecosystem, mediated
      by information and communication technologies in the health system. CONCLUSIONS:
      Telehealth should be composed of a set of activities in a computer mediated
      network promoting the translation of knowledge between research and health
      services.

PMID- 24897060
TI  - Thermo-catalytic decomposition of formaldehyde: a novel approach to produce
      mesoporous ZnO for enhanced photocatalytic activities.
AB  - A novel method, thermo-catalytic decomposition of formaldehyde, is used to
      synthesize mesoporous ZnO crystals with enhanced photocatalytic activities. The
      mechanism of the mesoporous formation is investigated by synthesizing a series of
      samples at various systems and characterizing them with FT-IR, EDS, XRD, SEM, and
      TEM. The results show that formaldehyde can be adsorbed on the crystal planes of
      ZnO during the crystal growth and can then be catalytically decomposed into CO,
      CO2 and H2 during a sintering process. Because of the formation and the escape of
      these gases, which act as templates, the crystalline particles of ZnO are forced
      to rearrange consistently, and pores are formed in the internal crystal. Also,
      porous TiO2 crystals have been obtained via the same approach. Photocatalytic
      tests indicate that a porous ZnO crystal has higher activity than that of a
      nonporous one. 

PMID- 24897058
TI  - Integration and continuity of Care in health care network models for frail older
      adults.
AB  - A detailed review was conducted of the literature on models evaluating the
      effectiveness of integrated and coordinated care networks for the older
      population. The search made use of the following bibliographic databases: Pubmed,
      The Cochrane Library, LILACS, Web of Science, Scopus and SciELO. Twelve articles
      on five different models were included for discussion. Analysis of the literature
      showed that the services provided were based on primary care, including services
      within the home. Service users relied on the integration of primary and hospital
      care, day centers and in-home and social services. Care plans and case management
      were key elements in care continuity. This approach was shown to be effective in
      the studies, reducing the need for hospital care, which resulted in savings for
      the system. There was reduced prevalence of functional loss and improved
      satisfaction and quality of life on the part of service users and their families.
      The analysis reinforced the need for change in the approach to health care for
      older adults and the integration and coordination of services is an efficient way
      of initiating this change. 

PMID- 24897061
TI  - Evaluation of the neurobehavioral screening tool in children with fetal alcohol
      spectrum disorders (FASD).
AB  - BACKGROUND: There is a growing need for validated tools to screen children at
      risk of fetal alcohol spectrum disorders (FASD). The Neurobehavioral Screening
      Tool (NST) is one of several promising screening measures for FASD, though
      further evidence is needed to establish the tool's psychometric utility.
      OBJECTIVE: To assess the predictive accuracy of the NST among children with an
      FASD diagnosis, with prenatal alcohol exposure (PAE) but no FASD diagnosis, and
      typically developing controls. METHOD: The NST was completed by caregivers of
      children ages 6 to 17, including 48 with FASD, 22 with PAE, and 32 typically
      developing non-exposed controls. Predictive accuracy coefficients were calculated
      using Nash et al. (2006) criteria, and compared against controls. An alternative
      scoring scheme was also investigated to determine optimum referral thresholds
      using item-level total scores. RESULTS: The NST yielded 62.5% sensitivity for
      participants with FASD and 50% for PAE. Specificity values were 100% with no
      typically developing control scoring positive. Within the FASD group there was a
      trend for higher sensitivity among adolescents aged 12 to17 (70.8%) compared with
      children aged 6 to 11 years (54.2%), p = 0.23. CONCLUSION: The findings support a
      growing body of literature evidencing psychometric promise for the clinical
      utility of the NST as an FASD screening tool, though further research on possible
      age-effects is warranted. The availability of a validated clinical screening tool
      for FASD, such as the NST, would aid in accurately screening a large number of
      children and lead to a timelier diagnostic referral.

PMID- 24897062
TI  - Eyes on new product development.

PMID- 24897063
TI  - Expression of androgen receptor and its association with estrogen receptor and
      androgen receptor downstream proteins in normal/benign breast luminal epithelium.
AB  - The androgen receptor (AR) is strongly expressed in the majority of breast
      carcinomas, but its role in breast hormonal carcinogenesis is not clear. We
      believe a better knowledge of the biology of normal/benign breast tissue will be
      the key to understanding this process. Using standard immunohistochemical
      staining on consecutive sections and dual immunohistochemical labeling, we
      studied the expression pattern of AR and estrogen receptor (ER) in normal/benign
      breast luminal epithelial cells. We found that most of the AR-positive cells are
      also ER positive, about 10% of the cells are AR-positive only, whereas ER
      positive only cells are uncommon, a distribution pattern of hormone receptor
      expression similar to what was revealed in invasive breast carcinomas. Whereas
      the expression of AR downstream proteins, such as prostate-specific antigen and
      gross cystic disease fluid protein, was either negative or unrelated to the AR
      status. We conclude that AR and ER expression status in invasive breast
      carcinomas reflects that of their progenitor cells in terminal duct lobular
      units. Our study did not reveal the expression of AR downstream proteins in
      normal/benign luminal epithelial cells at the regular immunohistochemistry level.

PMID- 24897064
TI  - Automated in situ hybridization for human papilloma virus.
AB  - With the increased number of requests for high-risk human papilloma virus in situ
      hybridization (HPV ISH), not only for uterine cervical squamous cell carcinoma
      (SCC) but also for biopsies and resections of oropharyngeal SCC, and fine needle
      aspiration cell blocks of metastatic SCC in cervical lymph nodes, we optimized an
      automated method to replace the manual one we had used. The new technique used
      the Leica BOND-maX or III immunostainer, already in use for immunohistochemical
      analysis, with the Enzo HPV type 16/18 and 6/11 probes. We stained 55 surgical
      biopsies and 41 cell blocks of oropharyngeal SCC. Sensitivity was 90% and 73% for
      biopsies and cell blocks, respectively, with a specificity of 100% in both. Stain
      is strong and crisp with no background. Turnaround time is short as runs are
      performed daily, with up to 30 slides per run. Technologists become trained in a
      few days, and the repeat rate is low. The only disadvantage is that ISH and IHC
      cannot be performed simultaneously. We highly recommend this automated technique
      for high-risk and low-risk HPV ISH and probably with other probes. 

PMID- 24897065
TI  - Immunohistochemical Investigation of BRAF p.V600E mutations in thyroid carcinoma
      using 2 separate BRAF antibodies.
AB  - BACKGROUND: Approximately 45% of papillary thyroid carcinomas harbor BRAF p.V600E
      mutations and current practice algorithms endorse molecular testing for BRAF
      p.V600E. We assessed the utility of immunohistochemistry to detect BRAF p.V600E
      mutations in thyroid carcinomas using 2 separate BRAF monoclonal antibodies: one
      that detects both mutant and wild-type protein (pan-BRAF) and another that
      detects only the mutant protein (mut-BRAF). METHODS: We selected 41 formalin
      fixed paraffin-embedded thyroid carcinomas (29 papillary, 1 follicular, 7
      medullary, and 4 anaplastic) from 37 thyroidectomies and 4 fine-needle
      aspirations. Immunohistochemistry was performed using a pan-BRAF (clone EP152Y)
      or a mut-BRAF (clone VE1) monoclonal antibody. Tumors were considered positive if
      >10% of neoplastic cells showed moderate (2+) or strong (3+) cytoplasmic
      staining. BRAF p.V600E mutations were confirmed by molecular pyrosequencing, the
      gold standard for statistical analysis. RESULTS: pan-BRAF reactivity was observed
      in 80.5% (n=33) of cases: 34.1% (n=14) harbored BRAF p.V600E mutations and 46.3%
      (n=19) were wild type. mut-BRAF reactivity was observed in 46.3% (n=19) of cases:
      34.1% (n=14) harbored BRAF p.V600E mutations and 12.2% (n=5) were wild type. The
      pan-BRAF antibody detected 14 more false positives (specificity: 29.6%, PPV:
      42.4%) compared with the mut-BRAF antibody (specificity: 61.5%, PPV: 73.7%), but
      both antibodies detected the same 5 false positives. No false negatives were
      detected with either antibody (sensitivity and NPV 100.0% for both). CONCLUSIONS:
      The suboptimal specificity and PPV limits the diagnostic utility of both
      antibodies to reliably detect BRAF p.V600E mutations in thyroid carcinoma.
      However, both antibodies provide excellent sensitivity and NPV and either could
      be used to exclude BRAF wild-type thyroid carcinomas before molecular testing.

PMID- 24897066
TI  - Immunohistochemistry in the diagnosis of thymic epithelial neoplasms.
AB  - The diagnosis of thymic epithelial neoplasms is normally rendered after careful
      evaluation of their histologic features. In some cases, however, the
      morphological heterogeneity or overlap with neoplasms of other organ systems can
      lead to diagnostic uncertainty. On the basis of this, the use of
      immunohistochemical stains as a diagnostic adjunct has become a popular tool.
      Although undoubtedly, immunohistochemistry has its role in the diagnosis of
      difficult cases, to date there are no specific markers that would distinguish
      thymic epithelial neoplasms from other tumors and interpretation of
      immunohistochemical results should only ever be made in conjunction with accurate
      morphologic analysis and careful clinical evaluation. This article will review
      the current knowledge of the immunohistochemical phenotype of thymic epithelial
      neoplasms with particular emphasis on its use for diagnostic purposes and the
      latest advances in this field. 

PMID- 24897067
TI  - Deparaffinization with mineral oil: a simple procedure for extraction of high
      quality DNA from archival formalin-fixed paraffin-embedded samples.
AB  - Extracting DNA from formalin-fixed paraffin-embedded (FFPE) archival samples
      remains difficult. Successful polymerase chain reactions (PCR) with DNA extracted
      from FFPE samples is still very low. We extracted DNA from 12 recent and old
      archival FFPE bone marrow trephine biopsies by use of a simple protocol on the
      basis of deparaffinization with molecular biology-grade mineral oil followed by
      DNA extraction with the Qiagen FFPE kit. Comparison of this deparaffinization
      method with standard protocols, for example, xylene or Hemo-D with subsequent
      rehydration using graded ethanols, was investigated. The quality and quantity of
      extracted DNA were tested by a combination of ultraviolet spectroscopy, analysis
      on a Caliper LabChip GX, and real-time PCR combined with high-resolution melt
      analysis. Highest quality PCR-amplifiable DNA was obtained by deparaffinization
      with mineral oil, whereas more variable results were obtained for the other 2
      deparaffinization procedures. This result was confirmed by real-time PCR and high
      resolution melt analysis. Besides improvements in the quality of extracted DNA,
      use of mineral oil for deparaffinization has the added benefit of decreased time
      (20 vs. 75 min) and a significant reduction of hands-on labor (1 step vs.
      multiple hands-on centrifugation and decanting steps). 

PMID- 24897068
TI  - Digital pathology for the validation of tissue microarrays in peripheral T-cell
      lymphomas.
AB  - Systematic validation of construction and analysis parameters when using tissue
      microarray (TMA) in rare, morphologically heterogenous entities such as
      peripheral T-cell lymphoma (PTCL) is not reported. We describe a tissue-saving
      virtual TMA to predetermine the number of cores needed to represent whole tissue
      sections (WTS) from the same biopsies, using automated and traditional manual
      methods for the quantification of immunohistochemical stains. Whole paraffin
      hematoxylin and eosin- and immunohistochemical (CD2, CD30, and Ki-67)-stained
      sections from 30 PTCLs were digitalized. A virtual TMA with six 1-mm cores per
      slide was designed to compare agreements in the immunohistochemical scoring.
      Using digital image analysis and manual stereological counting,
      immunohistochemical positivity was quantified. Associations were analyzed using
      the Bland-Altman and correlation plots. In PTCL, we report that 4 cores are
      required to represent WTS results (ie, agreement within +/-10%). High concordance
      was demonstrated between digital results obtained with WTS compared with 4-core
      virtual TMA (correlation coefficients: 0.89-0.98), and in the comparative
      evaluation of 4-core virtual TMA by digital image analysis versus manual
      stereology (correlation coefficients: 0.91 to 0.99). Virtual TMAs provide an
      efficient tool for optimizing and validating TMA construction parameters when
      planning a study. The method can be applied to the same tissues used in a
      subsequent formal study, without wasting scarce tissue resources. In PTCL, TMAs
      constructed with four 1-mm cores are representative of WTS. In parallel tests
      using TMAs and WTS from PTCLs, there is a high level of agreement comparing
      automated digital with manual stereological methods for the quantification of
      immunohistochemical biomarker staining. 

PMID- 24897070
TI  - Immunohistochemical Ki-67/KL1 double stains increase accuracy of Ki-67 indices in
      breast cancer and simplify automated image analysis.
AB  - BACKGROUND: Ki-67 immunohistochemical expression is a prognostic and predictive
      marker in many breast cancer studies. Instead of the conventional time-consuming
      score of Ki-67 single stains associated with low reproducibility, Ki-67/KL1
      double stains may facilitate fast, repeatable quantification by digital image
      analysis. This study aims to detect the difference in accuracy and precision
      between manual indices of single and double stains, to develop an automated
      quantification of double stains, and to explore the relation between automated
      indices and tumor characteristics when quantified in different regions: hot
      spots, global tumor areas, and invasive fronts. MATERIALS AND METHODS: Paraffin
      embedded, formalin-fixed tissue from 100 consecutive patients with invasive
      breast cancer was immunohistochemically stained for Ki-67 and Ki-67/KL1. Ki-67
      was manually scored in different regions by 2 observers and automated image
      analysis. RESULTS: Indices were predominantly higher for single stains than
      double stains (P<=0.002), yet the difference between observers was statistically
      significant (P<0.001) for both stains. The Pearson correlation coefficient for
      manual and automated indices ranged from 0.69 to 0.85 (P<0.001). Hot spots were
      slightly superior to other regions when correlating automated indices with tumor
      characteristics, for example, tumor size (P<0.001), grade (P=0.009), and estrogen
      receptor status (P=0.04). CONCLUSIONS: Although precision was unsatisfactory for
      manual indices of both stains, Ki-67 should be quantified on double stains to
      reach a higher accuracy. Automated indices correlated well with manual estimates
      and tumor characteristics, and they are thus possibly valuable tools in future
      exploration of Ki-67 in breast cancer.

PMID- 24897069
TI  - Reactive lymphoid hyperplasia of the terminal ileum: a benign (lymphoma-like)
      condition that may harbor aberrant immunohistochemical patterns or clonal
      immunoglobulin heavy chain gene rearrangements.
AB  - Small endoscopic biopsies of the terminal ileum may be difficult to assess for
      early involvement by lymphoma. Immunophenotypic and genotypic analyses are often
      utilized, but the performance of these studies in this setting is not well
      defined. Terminal ileal biopsies from 66 patients with prominent lymphoid
      hyperplasia and abnormal "lymphoma-like" morphology were evaluated by
      immunohistochemistry (IHC) for CD3, CD5, CD43, CD20, CD21, and CD10 expression
      and for IGH@ gene rearrangement by polymerase chain reaction using BIOMED-2
      primers. Patients ranged in age from 3 to 80 years. Indications for endoscopy
      included inflammatory bowel disease (29), diarrhea and/or abdominal pain (28),
      history of lymphoma (13), and others (4). Four biopsies with abnormal morphology
      had abnormal IHC and a clonal IGH@ peak; all were obtained from patients with a
      history of lymphoma and determined to be recurrent lymphoma. Three biopsies with
      abnormal morphology and abnormal IHC but no clonal IGH@ peak were obtained from
      patients with a history of lymphoma (2) and chronic diarrhea (1); all showed
      symptom resolution or remission of disease (mean follow-up, 37 mo). Eight
      biopsies with abnormal morphology but no abnormal IHC expression also had
      abnormal IGH@ results (4 clonal and 4 borderline). IGH@ evaluation of follow-up
      biopsies for these cases were nonclonal (7) or clonal, but with a different clone
      from the prior biopsy (1); follow-up of the 8 patients showed no evidence of
      lymphoma (mean, 37.8 mo). Abnormal IHC expression pattern or clonal IGH@
      rearrangement in endoscopic biopsies of the lymphoid-rich terminal ileum do not
      necessarily warrant a diagnosis of lymphoma. To prevent misdiagnosis, B-cell
      clonality studies should only be performed when there is strong clinical
      suspicion for lymphoma and compelling IHC data; the absence of a reproducible
      clone in repeat biopsy specimens may be useful in patients that do not have other
      clinical evidence of lymphoma. 

PMID- 24897071
TI  - Vascular pattern in enchondroma and chondrosarcoma: clinical and immunohistologic
      study.
AB  - INTRODUCTION: Although cartilaginous tumors have low microvascular density,
      vessels are important for the provision of nutrition so that the tumor can grow
      and generate metastasis. The aim of this study was to assess the value of the
      vascular pattern classification as a prognostic tool in chondrosarcomas (CSs) and
      its relation with vascular endothelial growth factor (VEGF) expression. MATERIALS
      AND METHODS: This was a retrospective study of 21 enchondromas and 57
      conventional CSs. Clinical data and outcome were retrieved from medical files.
      CSs histologic grades (on a scale of 1 to 3) were determined according to the
      World Health Organization classification. The vascular pattern (on a scale of A
      to C) was assessed through CD34, according to Kalinski. CD105 and VEGF were also
      evaluated. RESULTS: Poor outcome was significantly associated with vascular
      pattern groups B and C. Higher vascular pattern were 6.5 times more frequent in
      moderate-grade and high-grade CSs than in grade 1 CS. On multivariate analysis, a
      clear correlation was found between VEGF overexpression and B/C vascular
      patterns. Only 18 (benign and malignant) tumors stained for CD105. DISCUSSION:
      The results point to the use of the vascular pattern classification as a
      prognostic tool in CSs and to differentiate low-grade from moderate-grade/high
      grade CSs. Vascular pattern might be also used to complement histologic grade,
      VEGF immunostaining, and microvascular density, for indicating a patient's
      prognosis. Low-grade CSs develop under low neoangiogenesis, which conforms to the
      slow growth rate of these tumors.

PMID- 24897072
TI  - What can be concluded from blocking peptide controls?

PMID- 24897073
TI  - Validation of EP1 antibody clone for estrogen receptor immunohistochemistry in
      breast cancer.
AB  - Estrogen receptor (ER) tumor's status is critical for breast cancer management. A
      new rabbit antibody clone, EP1, is now available for ER status determination. The
      objective was to validate the EP1 antibody clone for its use in breast cancer ER
      status determination in a clinical setting against the previous standard, SP1.
      EP1 clone was assessed in 130 consecutive cases, including 50 ER-negative (<1% ER
      expression), 13 ER-low-positive (1% to 9% ER expression), and 67 ER-positive
      (>=10% ER expression). Using EP1 versus SP1, positive agreement (sensibility) was
      92.5% and negative agreement (specificity) was 100%, leading to an overall
      agreement of 95.4%. All discordant cases (n=6) were ER-low-positive. SP1 was
      remeasured in 13 ER-low-positive and in 11 ER-negative cases. Overall agreement
      between SP1 initial tumor status and reassessment was 70.8% in those negative and
      low-positive cases. In conclusion, EP1 antibody has been validated for use in
      breast cancer with a positive agreement >=90% and a negative agreement >=95%, as
      recommended. Also, overall agreement between EP1 and SP1 was as good as between
      the SP1 initial status and SP1 reassessment. 

PMID- 24897075
TI  - C4d staining as immunohistochemical marker in inflammatory myopathies.
AB  - The diagnosis of an inflammatory myopathy is often established based on basic
      histologic studies. Additional immunohistochemical studies are sometimes required
      to support the diagnosis and the classification of inflammatory myopathies.
      Staining for major histocompatibility complex 1 (MHC1) often shows increased
      sarcolemmal labeling in inflammatory myopathies. Endomysial capillary staining
      C5b-9 (membrane attack complex) is a feature that is reported as frequently
      associated with dermatomyositis. Immunohistochemical staining for C4d is widely
      used for various applications including the assessment of antibody-mediated
      rejection after solid organ transplantation. In the context of dermatomyositis,
      C4d staining has been described in skin biopsies but not in muscle biopsies. A
      total of 32 muscle biopsy specimens were examined. The hematoxylin and eosin
      stained slides were reviewed, and immunohistochemical studies for MHC1, C5b-9,
      and C4d were conducted. The staining observed for C5b-9 and C4d was compared.
      Overall, the staining pattern for C4d mirrored the one observed for C5b-9 in the
      examined muscle biopsy specimens. There was high and statistically significant
      (P<0.0001) correlation between the staining seen with these 2 antibodies. Both
      antibodies labeled the cytoplasm of degenerating necrotic myofibers. In addition,
      both antibodies showed distinct endomysial capillary labeling in a subset of
      dermatomyositis. Areas with perifascicular atrophy often exhibited the most
      prominent vascular labeling for C4d and C5b-9. In conclusion, C4d and C5b-9 show
      similar expression patterns in muscle biopsies of patients with inflammatory
      myopathies and both highlight the presence of vascular labeling associated with
      dermatomyositis. C4d antibodies are widely used and may offer an alternative for
      C5b-9 staining. 

PMID- 24897074
TI  - Myelofibrotic transformations of polycythemia vera and essential thrombocythemia
      are morphologically, biologically, and prognostically indistinguishable from
      primary myelofibrosis.
AB  - A fraction of polycythemia vera (PV) and essential thrombocythemia (ET) cases
      will, in time, undergo myelofibrotic transformation. In such cases, fibrosis may
      mask the diagnostic histologic features of the original underlying
      myeloproliferative neoplasm. Thus, confidently differentiating postfibrotic PV/ET
      from primary myelofibrosis (PMF) histologically may not be possible. It is
      controversial whether post-PV/ET myelofibrosis (MF) differs clinicopathologically
      from PMF, or whether these entities are biologically, clinically, and
      prognostically indistinguishable. To answer this question, we compared multiple
      candidate biological, morphologic, and prognostic parameters between 19
      postfibrotic ET/PV individuals and 18 PMF individuals. The postfibrotic ET/PV and
      PMF cases did not differ with regard to clinical outcome, cytogenetic
      abnormalities, serum lactate dehydrogenase level, peripheral blast count, bone
      marrow morphology, or grade of reticulin fibrosis. Only JAK2 allele burden, which
      was higher in the postfibrotic PV/ET population (P=0.011), differed between the 2
      groups. Cardinal morphologic features of PMF (ie, marrow cellularity,
      intrasinusoidal hematopoiesis, osteosclerosis, etc.) were commonly observed in
      post-PV/ET MF marrow biopsies, and only a minority of post-PV/ET MF marrow
      biopsies the retained diagnostic features of the primary myeloproliferative
      neoplasm (panmyelosis in PV and megakaryocytic hyperplasia in ET). Our study
      indicates that PMF and post-PV/ET MF are clinically and biologically
      indistinguishable. 

PMID- 24897076
TI  - A review on color normalization and color deconvolution methods in
      histopathology.
AB  - The histopathologists get the benefits of wide range of colored dyes to have much
      useful information about the lesions and the tissue compositions. Despite its
      advantages, the staining process comes up with quite complex variations in
      staining concentrations and correlations, tissue fixation types, and fixation
      time periods. Together with the improvements in computing power and with the
      development of novel image analysis methods, these imperfections have led to the
      emerging of several color normalization algorithms. This article is a review of
      the currently available digital color normalization methods for the bright field
      histopathology. We describe the proposed color normalization methodologies in
      detail together with the lesion and tissue types used in the corresponding
      experiments. We also present the quantitative validation approaches for each of
      the proposed methodology where available. 

PMID- 24897077
TI  - A new coumarin from Calophyllum hosei.
AB  - A new coumarin, hoseimarin (1), together with four other xanthones,
      trapezifolizanthone (2), osajaxanthone (3), beta-mangostin (4) and caloxanthone A
      (5), were isolated from the stem bark of Calophyllum hosei. The structures of
      these compounds were established by using spectroscopic analysis which included
      (1)H NMR, (13)C NMR, COSY, DEPT, HMQC and HMBC experiments. 

PMID- 24897079
TI  - Learning from big health care data.

PMID- 24897078
TI  - Risky music listening, permanent tinnitus and depression, anxiety, thoughts about
      suicide and adverse general health.
AB  - OBJECTIVE: To estimate the extent to which exposure to music through earphones or
      headphones with MP3 players or at discotheques and pop/rock concerts exceeded
      current occupational safety standards for noise exposure, to examine the extent
      to which temporary and permanent hearing-related symptoms were reported, and to
      examine whether the experience of permanent symptoms was associated with adverse
      perceived general and mental health, symptoms of depression, and thoughts about
      suicide. METHODS: A total of 943 students in Dutch inner-city senior-secondary
      vocational schools completed questionnaires about their sociodemographics, music
      listening behaviors and health. Multiple logistic regression analyses were used
      to examine associations. RESULTS: About 60% exceeded safety standards for
      occupational noise exposure; about one third as a result of listening to MP3
      players. About 10% of the participants experienced permanent hearing-related
      symptoms. Temporary hearing symptoms that occurred after using an MP3 player or
      going to a discotheque or pop/rock concert were associated with exposure to high
      volume music. However, compared to participants not experiencing permanent
      hearing-related symptoms, those experiencing permanent symptoms were less often
      exposed to high volume music. Furthermore, they reported at least two times more
      often symptoms of depression, thoughts about suicide and adverse self-assessed
      general and mental health. CONCLUSIONS: Risky music-listening behaviors continue
      up to at least the age of 25 years. Permanent hearing-related symptoms are
      associated with people's health and wellbeing. Participants experiencing such
      symptoms appeared to have changed their behavior to be less risky. In order to
      induce behavior change before permanent and irreversible hearing-related symptoms
      occur, preventive measurements concerning hearing health are needed.

PMID- 24897080
TI  - Fostering responsible data sharing through standards.

PMID- 24897081
TI  - Mini-Sentinel and regulatory science--big data rendered fit and functional.

PMID- 24897082
TI  - Once-weekly dalbavancin versus daily conventional therapy for skin infection.
AB  - BACKGROUND: Dalbavancin, a lipoglycopeptide antibiotic agent that is active
      against gram-positive pathogens, has a long plasma half-life, allowing for once
      weekly dosing. DISCOVER 1 and DISCOVER 2 were identically designed noninferiority
      trials of dalbavancin for the treatment of acute bacterial skin and skin
      structure infection. METHODS: We randomly assigned patients to receive
      dalbavancin intravenously on days 1 and 8 or vancomycin intravenously for at
      least 3 days with the option to switch to oral linezolid to complete 10 to 14
      days of therapy. The primary end point, early clinical response, required the
      cessation of spread of infection-related erythema and the absence of fever at 48
      to 72 hours. Secondary end points at the end of therapy included clinical status
      and investigator's assessment of outcome. RESULTS: Analysis of the primary end
      point showed noninferiority of dalbavancin in both DISCOVER 1 and DISCOVER 2. In
      the pooled analysis, 525 of 659 patients (79.7%) in the dalbavancin group and 521
      of 653 (79.8%) in the vancomycin-linezolid group had an early clinical response
      indicating treatment success (weighted difference, -0.1 percentage point; 95%
      confidence interval, -4.5 to 4.2). The outcomes were similar in the analyses by
      study and the pooled analyses of clinical status at the end of therapy and the
      investigator's assessment of outcome. For patients infected with Staphylococcus
      aureus, including methicillin-resistant S. aureus, clinical success was seen in
      90.6% of the patients treated with dalbavancin and 93.8% of those treated with
      vancomycin-linezolid. Adverse events and study days with an adverse event were
      less frequent in the dalbavancin group than in the vancomycin-linezolid group.
      The most common treatment-related adverse events in either group were nausea,
      diarrhea, and pruritus. CONCLUSIONS: Once-weekly intravenous dalbavancin was not
      inferior to twice-daily intravenous vancomycin followed by oral linezolid for the
      treatment of acute bacterial skin and skin-structure infection. (Funded by Durata
      Therapeutics; DISCOVER 1 and DISCOVER 2 ClinicalTrials.gov numbers, NCT01339091
      and NCT01431339.).

PMID- 24897083
TI  - Single-dose oritavancin in the treatment of acute bacterial skin infections.
AB  - BACKGROUND: Oritavancin is a lipoglycopeptide with bactericidal activity against
      gram-positive bacteria. Its concentration-dependent activity and prolonged half
      life allow for single-dose treatment. METHODS: We conducted a randomized, double
      blind trial in which adults with acute bacterial skin and skin-structure
      infections received either a single intravenous dose of 1200 mg of oritavancin or
      a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy
      end points were tested for noninferiority. The primary composite end point was
      defined as cessation of spreading or reduction in lesion size, absence of fever,
      and no need for administration of a rescue antibiotic 48 to 72 hours after
      administration of oritavancin. Secondary end points were clinical cure 7 to 14
      days after the end of treatment, as determined by a study investigator, and a
      reduction in lesion size of 20% or more 48 to 72 hours after administration of
      oritavancin. RESULTS: The modified intention-to-treat population comprised 475
      patients who received oritavancin and 479 patients who received vancomycin. All
      three efficacy end points met the prespecified noninferiority margin of 10
      percentage points for oritavancin versus vancomycin: primary end point, 82.3%
      versus 78.9% (95% confidence interval [CI] for the difference, -1.6 to 8.4
      percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95%
      CI for the difference, -5.5 to 4.7 percentage points); and proportion of patients
      with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for
      the difference, -0.5 to 8.6 percentage points). Efficacy outcomes measured
      according to type of pathogen, including methicillin-resistant Staphylococcus
      aureus, were similar in the two treatment groups. The overall frequency of
      adverse events was also similar, although nausea was more common among those
      treated with oritavancin. CONCLUSIONS: A single dose of oritavancin was
      noninferior to twice-daily vancomycin administered for 7 to 10 days for the
      treatment of acute bacterial skin and skin-structure infections caused by gram
      positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov
      number, NCT01252719.).

PMID- 24897086
TI  - Images in clinical medicine. Linear IgA bullous disease.

PMID- 24897087
TI  - Clinical problem-solving. Spot diagnosis.

PMID- 24897085
TI  - Adverse health effects of marijuana use.

PMID- 24897088
TI  - Pharmacology and the treatment of complicated skin and skin-structure infections.

PMID- 24897084
TI  - Pregnancy and infection.

PMID- 24897089
TI  - Causes of fever in outpatient Tanzanian children.

PMID- 24897091
TI  - Causes of fever in outpatient Tanzanian children.

PMID- 24897090
TI  - Causes of fever in outpatient Tanzanian children.

PMID- 24897092
TI  - Causes of fever in outpatient Tanzanian children.

PMID- 24897093
TI  - Management of skin abscesses.

PMID- 24897094
TI  - Management of skin abscesses.

PMID- 24897095
TI  - Management of skin abscesses.

PMID- 24897096
TI  - Global supply of health professionals.

PMID- 24897097
TI  - Global supply of health professionals.

PMID- 24897098
TI  - Global supply of health professionals.

PMID- 24897099
TI  - Global supply of health professionals.

PMID- 24897100
TI  - 23andMe and the FDA.

PMID- 24897101
TI  - 23andMe and the FDA.

PMID- 24897105
TI  - Images in clinical medicine. Tattoos and sarcoidosis.

PMID- 24897106
TI  - A new alkaloid from the fruit of Nandina domestica Thunb.
AB  - A new steroidal alkaloid, (20S,22R,24R)-24-ethyl-3-oxocholest-4-en-22-amino,
      named as nandsterine (1), together with 10 known alkaloids, palmatine (2), O
      methylbulbocapnine (3), nantenine (4), dehydronantenine (5), glaucine (6),
      didehydroglaucine (7), dehydrocorydaline (8), jatrorrhizine (9), magnoflorine
      (10) and berberine (11), was isolated from the fruit of Nandina domestica Thunb.
      Their structures were elucidated by using spectroscopic methods as well as by
      comparing with the published data. Compound 1 was a new class of steroidal
      alkaloid isolated from the family Berberidaceae, meanwhile compounds 2, 3, 6-8
      and 10 were obtained from N. domestica for the first time. Compound 1 exhibited
      cytotoxicity against HL-60 cells (human leukaemia) with IC50 values of 52.1 MUM.

PMID- 24897107
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health.

PMID- 24897108
TI  - Integrative analysis of transcriptional regulatory network and copy number
      variation in intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: Transcriptional regulatory network (TRN) is used to study conditional
      regulatory relationships between transcriptional factors and genes. However few
      studies have tried to integrate genomic variation information such as copy number
      variation (CNV) with TRN to find causal disturbances in a network. Intrahepatic
      cholangiocarcinoma (ICC) is the second most common hepatic carcinoma with high
      malignancy and poor prognosis. Research about ICC is relatively limited comparing
      to hepatocellular carcinoma, and there are no approved gene therapeutic targets
      yet. METHOD: We first constructed TRN of ICC (ICC-TRN) using forward-and-reverse
      combined engineering method, and then integrated copy number variation
      information with ICC-TRN to select CNV-related modules and constructed CNV-ICC
      TRN. We also integrated CNV-ICC-TRN with KEGG signaling pathways to investigate
      how CNV genes disturb signaling pathways. At last, unsupervised clustering method
      was applied to classify samples into distinct classes. RESULT: We obtained CNV
      ICC-TRN containing 33 modules which were enriched in ICC-related signaling
      pathways. Integrated analysis of the regulatory network and signaling pathways
      illustrated that CNV might interrupt signaling through locating on either genomic
      sites of nodes or regulators of nodes in a signaling pathway. In the end,
      expression profiles of nodes in CNV-ICC-TRN were used to cluster the ICC patients
      into two robust groups with distinct biological function features. CONCLUSION:
      Our work represents a primary effort to construct TRN in ICC, also a primary
      effort to try to identify key transcriptional modules based on their involvement
      of genetic variations shown by gene copy number variations (CNV). This kind of
      approach may bring the traditional studies of TRN based only on expression data
      one step further to genetic disturbance. Such kind of approach can easily be
      extended to other disease samples with appropriate data.

PMID- 24897109
TI  - Declining incidence of hepatitis C virus infection among people who inject drugs
      in a Canadian setting, 1996-2012.
AB  - BACKGROUND: People who inject drugs (PWID) are at high risk of hepatitis C virus
      (HCV) infection. Trends in HCV incidence and associated risk factors among PWID
      recruited between 1996 and 2012 in Vancouver, Canada were evaluated. METHODS:
      Data were derived from a long-term cohort of PWID in Vancouver. Trends in HCV
      incidence were evaluated. Factors associated with time to HCV infection were
      assessed using Cox proportional hazards regression. RESULTS: Among 2,589, 82% (n
      = 2,121) were HCV antibody-positive at enrollment. Among 364 HCV antibody
      negative participants with recent (last 30 days) injecting at enrollment, 126 HCV
      seroconversions were observed [Overall HCV incidence density: 8.6 cases/100
      person-years (py); 95% confidence interval (95% CI): 7.2, 10.1; HCV incidence
      density among those with injecting during follow-up: 11.5 cases/100 py; 95% CI
      9.7, 13.6]. The overall HCV incidence density declined significantly from
      25.0/100 py (95% CI: 20.2, 30.3) in 1996-99, as compared to 6.0/100 py (95% CI:
      4.1, 8.5) in 2000-2005, and 3.1/100 py (95% CI: 2.0, 4.8) in 2006-2012. Among
      those with injecting during follow-up, the overall HCV incidence density declined
      significantly from 27.9/100 py (95% CI: 22.6, 33.6) in 1996-99, as compared to
      7.5/100 py (95% CI: 5.1, 10.6) in 2000-2005, and 4.9/100 py (95% CI: 3.1, 7.4) in
      2006-2012. Unstable housing, HIV infection, and injecting of cocaine, heroin and
      methamphetamine were independently associated with HCV seroconversion.
      CONCLUSIONS: HCV incidence has dramatically declined among PWID in this setting.
      However, improved public health strategies to prevent and treat HCV are urgently
      required to reduce HCV-associated morbidity and mortality.

PMID- 24897111
TI  - A novel cassette method for probe evaluation in the designed biochips.
AB  - A critical step in biochip design is the selection of probes with identical
      hybridisation characteristics. In this article we describe a novel method for
      evaluating DNA hybridisation probes, allowing the fine-tuning of biochips, that
      uses cassettes with multiple probes. Each cassette contains probes in equimolar
      proportions so that their hybridisation performance can be assessed in a single
      reaction. The model used to demonstrate this method was a series of probes
      developed to detect TORCH pathogens. DNA probes were designed for Toxoplasma
      gondii, Chlamidia trachomatis, Rubella, Cytomegalovirus, and Herpes virus and
      these were used to construct the DNA cassettes. Five cassettes were constructed
      to detect TORCH pathogens using a variety of genes coding for membrane proteins,
      viral matrix protein, an early expressed viral protein, viral DNA polymerase and
      the repetitive gene B1 of Toxoplasma gondii. All of these probes, except that for
      the B1 gene, exhibited similar profiles under the same hybridisation conditions.
      The failure of the B1 gene probe to hybridise was not due to a position effect,
      and this indicated that the probe was unsuitable for inclusion in the biochip.
      The redesigned probe for the B1 gene exhibited identical hybridisation properties
      to the other probes, suitable for inclusion in a biochip. 

PMID- 24897110
TI  - Impact of leisure-time physical activity on glycemic control and cardiovascular
      risk factors in Japanese patients with type 2 diabetes mellitus: the Fukuoka
      Diabetes Registry.
AB  - AIMS/HYPOTHESIS: The effects of leisure-time physical activity (LTPA) on glycemia
      and cardiovascular risk factors are not fully understood in Asian type 2 diabetic
      patients, who are typically non-obese. We studied associations between LTPA and
      glycemia and cardiovascular risk factors in Japanese type 2 diabetic patients.
      METHODS: A total of 4,870 Japanese type 2 diabetic patients aged >= 20 years were
      divided into eight groups according to their LTPA. We investigated associations
      between the amount and intensity levels of physical activity (PA) and glycemic
      control, insulin sensitivity, cardiovascular risk factors, and low-grade systemic
      inflammation in a cross-sectional study. RESULTS: LTPA was dose-dependently
      associated with body mass index (BMI), waist circumference, hemoglobin A1c
      (HbA1c), fasting plasma glucose, homeostasis model assessment of insulin
      resistance, triglyceride, high density lipoprotein cholesterol, high sensitivity
      C-reactive protein, and prevalence of metabolic syndrome, but not with blood
      pressure, low density lipoprotein cholesterol or adiponectin. The amount of PA
      required to lower HbA1c was greater than that required to improve cardiovascular
      risk factors. LTPA was inversely associated with HbA1c in non-obese participants
      but not in obese participants after multivariate adjustments for age, sex,
      duration of diabetes, current smoking, current drinking, energy intake,
      cardiovascular diseases, depressive symptoms, and treatment of diabetes. Higher
      intensity LTPA, not lower-intensity LTPA was associated with HbA1c after
      multivariate adjustments with further adjustment including BMI.
      CONCLUSIONS/INTERPRETATION: LTPA was dose-dependently associated with better
      glycemic control and amelioration of some cardiovascular risk factors in Japanese
      type 2 diabetic patients. In addition, increased higher-intensity LTPA may be
      appropriate for glycemic control.

PMID- 24897112
TI  - Learning curve and interobserver agreement of confocal laser endomicroscopy for
      detecting precancerous or early-stage esophageal squamous cancer.
AB  - BACKGROUND: Confocal laser endomicroscopy (CLE) can provide in vivo subcellular
      resolution images of esophageal lesions. However, the learning curve in
      interpreting CLE images of precancerous or early-stage esophageal squamous cancer
      is unknown. The goal of this study is to evaluate the diagnostic accuracy and
      inter-observer agreement for differentiating esophageal lesions in CLE images
      among experienced and inexperienced observers and to assess the learning curve.
      METHOD: After a short training, 8 experienced and 14 inexperienced endoscopists
      evaluated in sequence 4 sets of high-quality CLE images. Their diagnoses were
      corrected and discussed after each set. For each image, the diagnostic results,
      confidence in diagnosis, quality and time to evaluate were recorded. RESULTS:
      Overall, diagnostic accuracy was greater for the second, third, fourth set of
      images as compared with the initial set (odds ratio [OR] 2.01, 95% CI 1.22-3.31;
      7.95, 3.74-16.87; and 6.45, 3.14-13.27), respectively, with no difference between
      the third and fourth sets in accuracy (p = 0.67). Previous experience affected
      the diagnostic accuracy only in the first set of images (OR 3.70, 1.87-7.29,
      p<0.001). Inter-observer agreement was higher for experienced than inexperienced
      endoscopists (0.732 vs. 0.666, p<0.01). CONCLUSION: CLE is a promising technology
      that can be quickly learned after a short training period; previous experience is
      associated with diagnostic accuracy only at the initial stage of learning.

PMID- 24897113
TI  - Transcription factor Ets1 regulates expression of thioredoxin-interacting protein
      and inhibits insulin secretion in pancreatic beta-cells.
AB  - Long-term activation of extracellular-regulated kinase (ERK1/2) pathway has been
      shown to cause glucotoxicity and inhibit insulin gene expression in beta-cells.
      Transcription factor Ets1 is activated by ERK1/2-mediated phosphorylation at the
      Thr38 residue. We hypothesize that Ets1 plays an important role in mediating
      ERK1/2 induced glucotoxicity in beta-cells. We determined the role of Ets1 in
      Min6 cells and isolated mouse islets using overexpression and siRNA mediated
      knockdown of Ets1. The results show that Ets1 was localized in insulin-staining
      positive cells but not in glucagon-staining positive cells. Overexpression of
      Ets1 reduced glucose-stimulated insulin secretion in primary mouse islets.
      Overexpression of Ets1 in Min6 beta-cells and mouse islets increased expression
      of thioredoxin-interacting protein (TXNIP). Conversely, knockdown of Ets1 by
      siRNA reduced expression of TXNIP in Min6 cells. Ets1 was associated with the
      txnip promoter in min6 cells and transfection of 293 cells with Ets1 and p300
      synergistically increased txnip promoter reporter activity. Moreover,
      overexpression of Ets1 inhibited Min6 cell proliferation. Our results suggest
      that Ets1, by promoting TXNIP expression, negatively regulates beta-cell
      function. Thus, over-activation of Ets1 may contribute to diet-induced beta-cell
      dysfunction. 

PMID- 24897115
TI  - The seeding and cultivation of a tropical species of filamentous Ulva for algal
      biomass production.
AB  - Filamentous species of Ulva are ideal for cultivation because they are robust
      with high growth rates and maintained across a broad range of environments.
      Temperate species of filamentous Ulva are commercially cultivated on nets which
      can be artificially 'seeded' under controlled conditions allowing for a high
      level of control over seeding density and consequently biomass production. This
      study quantified for the first time the seeding and culture cycle of a tropical
      species of filamentous Ulva (Ulva sp. 3) and identified seeding density and
      nursery period as key factors affecting growth and biomass yield. A seeding
      density of 621,000 swarmers m(-1) rope in combination with a nursery period of
      five days resulted in the highest growth rate and correspondingly the highest
      biomass yield. A nursery period of five days was optimal with up to six times the
      biomass yield compared to ropes under either shorter or longer nursery periods.
      These combined parameters of seeding density and nursery period resulted in a
      specific growth rate of more than 65% day(-1) between 7 and 10 days of outdoor
      cultivation post-nursery. This was followed by a decrease in growth through to 25
      days. This study also demonstrated that the timing of harvest is critical as the
      maximum biomass yield of 23.0 +/- 8.8 g dry weight m(-1) (228.7 +/- 115.4 g fresh
      weight m(-1)) was achieved after 13 days of outdoor cultivation whereas biomass
      degraded to 15.5 +/- 7.3 g dry weight m(-1) (120.2 +/- 71.8 g fresh weight m(-1))
      over a longer outdoor cultivation period of 25 days. Artificially seeded ropes of
      Ulva with high biomass yields over short culture cycles may therefore be an
      alternative to unattached cultivation in integrated pond-based aquaculture
      systems.

PMID- 24897114
TI  - Immune responses and hypercoagulation in ERT for Pompe disease are mutation and
      rhGAA dose dependent.
AB  - Enzyme replacement therapy (ERT) with recombinant human acid-alpha-glucosidase
      (rhGAA) is the only FDA approved therapy for Pompe disease. Without ERT, severely
      affected individuals (early onset) succumb to the disease within 2 years of life.
      A spectrum of disease severity and progression exists depending upon the type of
      mutation in the GAA gene (GAA), which in turn determines the amount of defective
      protein produced and its enzymatic activity. A large percent of the early onset
      patients are also cross reactive immunological material negative (CRIM-) and
      develop high titer immune responses to ERT with rhGAA. New insights from our
      studies in pre-clinical murine models reveal that the type of Gaa mutation has a
      profound effect on the immune responses mounted against ERT and the associated
      toxicities, including activation of clotting factors and disseminated
      intravascular coagulation (DIC). Additionally, the mouse strain affects outcomes,
      suggesting the influence of additional genetic components or modifiers. High
      doses of rhGAA (20 mg/kg) are currently required to achieve therapeutic benefit.
      Our studies indicate that lower enzyme doses reduce the antibody responses to
      rhGAA, reduce the incidence of immune toxicity and avoid ERT-associated
      anaphylaxis. Therefore, development of rhGAA with increased efficacy is warranted
      to limit immunotoxicities. 

PMID- 24897116
TI  - Patterning of nanocrystalline cellulose gel phase by electrodissolution of a
      metallic electrode.
AB  - At high concentration or in the presence of electrolytes and organic solvents,
      solutions of cellulose nanocrystals (CNCs) can form gels exhibiting optical
      properties similar to the ones of liquid crystal phases. In an attempt to pattern
      such a gel phase, we have studied the electrodissolution of a metallic electrode
      in a water suspension of carboxylated CNCs (cCNCs). Depending on the metal used,
      the electrodissolution process was observed at a different positive potential. In
      the case of copper the minimum potential at which we could observe optically the
      growth of the gel phase was 200 mV. The growth rate was current limited
      indicating that the process was controlled by the electrodissolution of the
      copper electrode. This hypothesis was confirmed by using circular and square
      copper patterns as positive electrodes. In both cases, the consumption of the
      electrode material was observed optically and correlated with the growth of the
      gel phase. 

PMID- 24897117
TI  - Frizzled 7 expression is positively regulated by SIRT1 and beta-catenin in breast
      cancer cells.
AB  - The Wnt signaling pathway is often chronically activated in diverse human tumors,
      and the Frizzled (FZD) family of receptors for Wnt ligands, are central to
      propagating oncogenic signals in a beta-catenin-dependent and independent manner.
      SIRT1 is a class III histone deacetylase (HDAC) that deacetylates histone and non
      histone proteins to regulate gene transcription and protein function. We
      previously demonstrated that SIRT1 loss of function led to a significant decrease
      in the levels of Dishevelled (Dvl) proteins. To further explore this connection
      between the sirtuins and components of the Wnt pathway, we analyzed sirtuin
      mediated regulation of FZD proteins. Here we explore the contribution of sirtuin
      deacetylases in promoting constitutive Wnt pathway activation in breast cancer
      cells. We demonstrate that the use of small molecule inhibitors of SIRT1 and
      SIRT2, and siRNA specific to SIRT1, all reduce the levels of FZD7 mRNA. We
      further demonstrate that pharmacologic inhibition of SIRT1/2 causes a marked
      reduction in FZD7 protein levels. Additionally, we show that beta-catenin and c
      Jun occupy the 7 kb region upstream of the transcription start site of the FZD7
      gene, and SIRT1 inhibition leads to a reduction in the occupancy of both beta
      catenin and c-Jun at points along this region. This work uncovers a new mechanism
      for the regulation of FZD7 and provides a critical new link between the sirtuins
      and FZD7, one of the earliest nodal points from which oncogenic Wnt signaling
      emanates. This study shows that inhibition of specific sirtuins may provide a
      unique strategy for inhibiting the constitutively active Wnt pathway at the level
      of the receptor. 

PMID- 24897118
TI  - Spatiotemporal dynamics of DENV-2 Asian-American genotype lineages in the
      Americas.
AB  - The Asian/American (AS/AM) genotype of dengue virus type 2 (DENV-2) has been
      evolving in the Americas over the last 30 years, leading to several waves of
      dengue epidemics and to the emergence of different viral lineages in the region.
      In this study, we investigate the spatiotemporal dissemination pattern of the
      DENV-2 lineages at a regional level. We applied phylogenetic and phylogeographic
      analytical methods to a comprehensive data set of 582 DENV-2 E gene sequences of
      the AS/AM genotype isolated from 29 different American countries over a period of
      30 years (1983 to 2012). Our study reveals that genetic diversity of DENV-2 AS/AM
      genotype circulating in the Americas mainly resulted from one single founder
      event and can be organized in at least four major lineages (I to IV), which
      emerged in the Caribbean region at the early 1980s and then spread and die out
      with different dynamics. Lineages I and II dominate the epidemics in the
      Caribbean region during the 1980s and early 1990 s, lineage III becomes the
      prevalent DENV-2 one in the Caribbean and South America during the 1990 s,
      whereas lineage IV dominates the epidemics in South and Central America during
      the 2000s. Suriname and Guyana seem to represent important entry points for DENV
      2 from the Lesser Antilles to South America, whereas Venezuela, Brazil and
      Nicaragua were pointed as the main secondary hubs of dissemination to other
      mainland countries. Our study also indicates that DENV-2 AS/AM genotype was
      disseminated within South America following two main routes. The first route hits
      Venezuela and the western side of the Andes, while the second route mainly hits
      Brazil and the eastern side of the Andes. The phenomenon of DENV-2 lineage
      replacement across successive epidemic outbreaks was a common characteristic in
      all American countries, although the timing of lineage replacements greatly vary
      across locations.

PMID- 24897119
TI  - A MLVA genotyping scheme for global surveillance of the citrus pathogen
      Xanthomonas citri pv. citri suggests a worldwide geographical expansion of a
      single genetic lineage.
AB  - MultiLocus Variable number of tandem repeat Analysis (MLVA) has been extensively
      used to examine epidemiological and evolutionary issues on monomorphic human
      pathogenic bacteria, but not on bacterial plant pathogens of agricultural
      importance albeit such tools would improve our understanding of their
      epidemiology, as well as of the history of epidemics on a global scale.
      Xanthomonas citri pv. citri is a quarantine organism in several countries and a
      major threat for the citrus industry worldwide. We screened the genomes of
      Xanthomonas citri pv. citri strain IAPAR 306 and of phylogenetically related
      xanthomonads for tandem repeats. From these in silico data, an optimized MLVA
      scheme was developed to assess the global diversity of this monomorphic
      bacterium. Thirty-one minisatellite loci (MLVA-31) were selected to assess the
      genetic structure of 129 strains representative of the worldwide pathological and
      genetic diversity of X. citri pv. citri. Based on Discriminant Analysis of
      Principal Components (DAPC), four pathotype-specific clusters were defined. DAPC
      cluster 1 comprised strains that were implicated in the major geographical
      expansion of X. citri pv. citri during the 20th century. A subset of 12 loci
      (MLVA-12) resolved 89% of the total diversity and matched the genetic structure
      revealed by MLVA-31. MLVA-12 is proposed for routine epidemiological
      identification of X. citri pv. citri, whereas MLVA-31 is proposed for
      phylogenetic and population genetics studies. MLVA-31 represents an opportunity
      for international X. citri pv. citri genotyping and data sharing. The MLVA-31
      data generated in this study was deposited in the Xanthomonas citri genotyping
      database (http://www.biopred.net/MLVA/). 

PMID- 24897120
TI  - The carry-over effect of competition in task-sharing: evidence from the joint
      Simon task.
AB  - The Simon effect, that is the advantage of the spatial correspondence between
      stimulus and response locations when stimulus location is a task-irrelevant
      dimension, occurs even when the task is performed together by two participants,
      each performing a go/no-go task. Previous studies showed that this joint Simon
      effect, considered by some authors as a measure of self-other integration, does
      not emerge when during task performance co-actors are required to compete. The
      present study investigated whether and for how long competition experienced
      during joint performance of one task can affect performance in a following joint
      Simon task. In two experiments, we required pairs of participants to perform
      together a joint Simon task, before and after jointly performing together an
      unrelated non-spatial task (the Eriksen flanker task). In Experiment 1,
      participants always performed the joint Simon task under neutral instructions,
      before and after performing the joint flanker task in which they were explicitly
      required either to cooperate with (i.e., cooperative condition) or to compete
      against a co-actor (i.e., competitive condition). In Experiment 2, they were
      required to compete during the joint flanker task and to cooperate during the
      subsequent joint Simon task. Competition experienced in one task affected the way
      the subsequent joint task was performed, as revealed by the lack of the joint
      Simon effect, even though, during the Simon task participants were not required
      to compete (Experiment 1). However, prior competition no longer affected
      subsequent performance if a new goal that created positive interdependence
      between the two agents was introduced (Experiment 2). These results suggest that
      the emergence of the joint Simon effect is significantly influenced by how the
      goals of the co-acting individuals are related, with the effect of competition
      extending beyond the specific competitive setting and affecting subsequent
      interactions. 

PMID- 24897122
TI  - Kinetic validation of the models for P-glycoprotein ATP hydrolysis and vanadate
      induced trapping. Proposal for additional steps.
AB  - P-Glycoprotein, a member of the ATP-binding cassette (ABC) superfamily, is a
      multidrug transporter responsible for cellular efflux of hundreds of structurally
      unrelated compounds, including natural products, many clinically used drugs and
      anti-cancer agents. Expression of P-glycoprotein has been linked to multidrug
      resistance in human cancers. ABC transporters are driven by ATP hydrolysis at
      their two cytoplasmic nucleotide-binding domains, which interact to form a closed
      ATP-bound sandwich dimer. Intimate knowledge of the catalytic cycle of these
      proteins is clearly essential for understanding their mechanism of action. P
      Glycoprotein has been proposed to hydrolyse ATP by an alternating mechanism, for
      which there is substantial experimental evidence, including inhibition of
      catalytic activity by trapping of ortho-vanadate at one nucleotide-binding
      domain, and the observation of an asymmetric occluded state. Despite many studies
      of P-glycoprotein ATPase activity over the past 20 years, no comprehensive
      kinetic analysis has yet been carried out, and some puzzling features of its
      behaviour remain unexplained. In this work, we have built several progressively
      more complex kinetic models, and then carried out simulations and detailed
      analysis, to test the validity of the proposed reaction pathway employed by P
      glycoprotein for ATP hydrolysis. To establish kinetic parameters for the
      catalytic cycle, we made use of the large amount of published data on ATP
      hydrolysis by hamster P-glycoprotein, both purified and in membrane vesicles. The
      proposed kinetic scheme(s) include a high affinity priming reaction for binding
      of the first ATP molecule, and an independent pathway for ADP binding outside the
      main catalytic cycle. They can reproduce to varying degrees the observed behavior
      of the protein's ATPase activity and its inhibition by ortho-vanadate. The
      results provide new insights into the mode of action of P-glycoprotein, and some
      hypotheses about the nature of the occluded nucleotide-bound state. 

PMID- 24897125
TI  - Identifying and characterizing key nodes among communities based on electrical
      circuit networks.
AB  - Complex networks with community structures are ubiquitous in the real world.
      Despite many approaches developed for detecting communities, we continue to lack
      tools for identifying overlapping and bridging nodes that play crucial roles in
      the interactions and communications among communities in complex networks. Here
      we develop an algorithm based on the local flow conservation to effectively and
      efficiently identify and distinguish the two types of nodes. Our method is
      applicable in both undirected and directed networks without a priori knowledge of
      the community structure. Our method bypasses the extremely challenging problem of
      partitioning communities in the presence of overlapping nodes that may belong to
      multiple communities. Due to the fact that overlapping and bridging nodes are of
      paramount importance in maintaining the function of many social and biological
      networks, our tools open new avenues towards understanding and controlling real
      complex networks with communities accompanied with the key nodes. 

PMID- 24897124
TI  - Impact of transgenic wheat with wheat yellow mosaic virus resistance on microbial
      community diversity and enzyme activity in rhizosphere soil.
AB  - The transgenic wheat line N12-1 containing the WYMV-Nib8 gene was obtained
      previously through particle bombardment, and it can effectively control the wheat
      yellow mosaic virus (WYMV) disease transmitted by Polymyxa graminis at turngreen
      stage. Due to insertion of an exogenous gene, the transcriptome of wheat may be
      altered and affect root exudates. Thus, it is important to investigate the
      potential environmental risk of transgenic wheat before commercial release
      because of potential undesirable ecological side effects. Our 2-year study at two
      different experimental locations was performed to analyze the impact of
      transgenic wheat N12-1 on bacterial and fungal community diversity in rhizosphere
      soil using polymerase chain reaction-denaturing gel gradient electrophoresis (PCR
      DGGE) at four growth stages (seeding stage, turngreen stage, grain-filling stage,
      and maturing stage). We also explored the activities of urease, sucrase and
      dehydrogenase in rhizosphere soil. The results showed that there was little
      difference in bacterial and fungal community diversity in rhizosphere soil
      between N12-1 and its recipient Y158 by comparing Shannon's, Simpson's diversity
      index and evenness (except at one or two growth stages). Regarding enzyme
      activity, only one significant difference was found during the maturing stage at
      Xinxiang in 2011 for dehydrogenase. Significant growth stage variation was
      observed during 2 years at two experimental locations for both soil microbial
      community diversity and enzyme activity. Analysis of bands from the gel for
      fungal community diversity showed that the majority of fungi were uncultured. The
      results of this study suggested that virus-resistant transgenic wheat had no
      adverse impact on microbial community diversity and enzyme activity in
      rhizosphere soil during 2 continuous years at two different experimental
      locations. This study provides a theoretical basis for environmental impact
      monitoring of transgenic wheat when the introduced gene is derived from a virus. 

PMID- 24897126
TI  - RET variants and haplotype analysis in a cohort of Czech patients with
      Hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and
      submucosal plexuses in variable length of the intestine. This study investigated
      the influence and a possible modifying function of RET proto-oncogene's single
      nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype
      of the disease in Czech patients. Genotyping of 14 SNPs was performed using
      TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and
      generated haplotypes were statistically evaluated using chi-square test and the
      association with the risk of HSCR was estimated by odds ratio. SNP analysis
      revealed significant differences in frequencies of 11 polymorphic RET variants
      between 162 HSCR patients and 205 unaffected controls. Particularly variant
      alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2),
      rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with
      increased risk of HSCR (p<0.00000) and were over-represented in males vs.
      females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons
      7, 11, 15) had a protective role. The haploblock comprising variants in intron 1
      and exon 2 was constructed. It represented a high risk of HSCR, however, the
      influence of other variants was also found after pruning from effect of this
      haploblock. Clustering patients according to genotype status in haploblock
      revealed a strong co-segregation with several SNPs and pointed out the
      differences between long and short form of HSCR. This study involved a large
      number of SNPs along the entire RET proto-oncogene with demonstration of their
      risk/protective role also in haplotype and diplotype analysis in the Czech
      population. The influence of some variant alleles on the aggressiveness of the
      disease and their role in gender manifestation differences was found. These data
      contribute to worldwide knowledge of the genetics of HSCR. 

PMID- 24897127
TI  - Contextual determinants and alcohol control policies in the United Kingdom.
AB  - In the United Kingdom, between 1960 and the 2000s, there were many
      sociodemographic and economic factors that played a part in the changing picture
      of alcohol consumption and its related harm. This paper describes some of these
      variables along with the political measures that were identified as correlated
      with changes in consumption and harm. The resulting picture is unclear. No
      consistent pattern was identified among the variables analyzed. Beverage choice
      changed over time with a reduction in beer consumption and an increase in wines
      and spirits. Nevertheless, the overall picture showed an increase in total
      alcohol consumption and resulting harm. 

PMID- 24897128
TI  - Protecting athletes and ensuring sports--free of doping.

PMID- 24897129
TI  - Sensing mechanism for biothiols chemosensor DCO: roles of excited-state hydrogen
      bonding and intramolecular charge transfer.
AB  - The biothiols sensing mechanism of (E)-7-(diethylamino)-3-(2-nitrovinyl)-2H
      chromen-2-one (DCO) has been investigated using the density functional theory
      (DFT) and time-dependent DFT methods. The theoretical results indicate that the
      excited-state intermolecular hydrogen bonding (H-B) plays an important role for
      the biothiols sensing mechanism of the fluorescence sensor DCO. Multiple H-B
      interaction sites exist in DCO and in its Michael addition product DCOT, which
      then induce the formation of the H-B complexes with water molecules, DCOH2 and
      DCOTH4. In the first excited state, the intermolecular H-Bs between water
      molecule and DCO in DCOH2 are cooperatively and generally strengthened and thus
      induced the weak fluorescence emission of DCO, while the cooperative H-Bs between
      water molecule and DCOT in DCOTH4 are overall weakened and thus responsible for
      the enhanced fluorescence emission of DCOT. Moreover, the theoretical results
      suggest that the blue shift of the UV-Vis absorption spectrum of DCOT can be
      attributed to the relatively weak excited-state intramolecular charge transfer in
      DCOT compared to DCO. 

PMID- 24897130
TI  - Colloid mobilization and transport during capillary fringe fluctuations.
AB  - Capillary fringe fluctuations due to changing water tables lead to displacement
      of air-water interfaces in soils and sediments. These moving air-water interfaces
      can mobilize colloids. We visualized colloids interacting with moving air-water
      interfaces during capillary fringe fluctuations by confocal microscopy. We
      simulated capillary fringe fluctuations in a glass-bead-filled column. We studied
      four specific conditions: (1) colloids suspended in the aqueous phase, (2)
      colloids attached to the glass beads in an initially wet porous medium, (3)
      colloids attached to the glass beads in an initially dry porous medium, and (4)
      colloids suspended in the aqueous phase with the presence of a static air bubble.
      Confocal images confirmed that the capillary fringe fluctuations affect colloid
      transport behavior. Hydrophilic negatively charged colloids initially suspended
      in the aqueous phase were deposited at the solid-water interface after a drainage
      passage, but then were removed by subsequent capillary fringe fluctuations. The
      colloids that were initially attached to the wet or dry glass bead surface were
      detached by moving air-water interfaces in the capillary fringe. Hydrophilic
      negatively charged colloids did not attach to static air-bubbles, but hydrophobic
      negatively charged and hydrophilic positively charged colloids did. Our results
      demonstrate that capillary fringe fluctuations are an effective means for colloid
      mobilization. 

PMID- 24897132
TI  - New developments in comorbidities of atopic dermatitis.

PMID- 24897131
TI  - Chromogranin A as a biomarker of disease activity and biologic therapy in
      inflammatory bowel disease: a prospective observational study.
AB  - OBJECTIVE: To access the correlation of Chromogranin A (CgA) with inflammatory
      bowel disease (IBD) activity and responsiveness to medical therapy. MATERIAL AND
      METHODS: A prospective observational study was conducted in 56 patients with
      moderate ulcerative colitis (UC) or Crohn's disease (CD) (UC, n = 29, CD, n =
      27), 17 patients with irritable bowel syndrome and predominant diarrhea (IBS-D)
      and 40 healthy volunteers. IBD patients were treated by biologics (infliximab or
      adalimumab) or conventional agents (aminosalicylates, thiopurines or methotrexate
      and steroids) and were classified according to their treatment in two groups.
      Serum CgA was measured at baseline and 4-week posttreatment period. RESULTS:
      Serum CgA was significantly higher in IBD patients than in those with IBS-D or
      healthy volunteers (p < 0.01). Furthermore, serum CgA was markedly increased in
      CD patients than in UC patients (p < 0.01). CgA value was significantly reduced
      in 'biologic' group (24 IBD patients, UC, n = 15, CD, n = 9) at 4-week
      posttreatment period (p < 0.01), while 18/24 (72%) patients were already in
      remission during that time. In contrast, CgA value was significantly increased in
      the 'conventional' treatment group (32 IBD patients, UC, n = 14, CD, n = 18)
      between the two visits (p < 0.01), although 22/32 (69%) patients were in
      remission during the 4-week posttreatment period. CONCLUSION: CgA appears to be a
      reliable marker of disease activity in IBD patients and especially in those who
      received biologic therapy. IBS-D patients presented normal CgA values.

PMID- 24897133
TI  - ICD-10: do not be lulled by the postponement.

PMID- 24897134
TI  - Congenital candidiasis: an uncommon skin eruption presenting at birth.
AB  - We present the case of a preterm neonate who was born with respiratory distress
      and a papulovesicular rash that was diagnosed as congenital candidiasis (CC). The
      mother was asymptomatic. The cutaneous eruption and respiratory distress improved
      following treatment with systemic antifungals. Congenital candidiasis ranges in
      presentation from isolated cutaneous involvement to severe multisystem disease.
      Given its rarity among neonatal skin eruptions, heightened suspicion is required
      for prompt diagnosis and treatment. 

PMID- 24897135
TI  - Cutaneous alternariosis in a renal transplant recipient.
AB  - Alternariosis is a fungal infection that is usually described in
      immunocompromised patients. We report a case of cutaneous alternariosis in a
      renal transplant recipient caused by Alternaria tenuissima. The diagnosis was
      supported by histopathologic (ie, yeastlike cells, filamentous structures) and
      mycologic findings from a cutaneous biopsy. Cutaneous lesions regressed 1 month
      following a decrease in the dosage of immunosuppressive therapy. The patient also
      was treated with intravenous amphotericin B followed by oral fluconazole without
      improvement. Cryotherapy remarkably accelerated healing of the lesions. 

PMID- 24897136
TI  - Multicentric reticulohistiocytosis: contrasting presentations in 2 Hispanic
      patients.
AB  - Multicentric reticulohistiocytosis (MR) is a rare debilitating disease that
      involves the skin and joints. It most commonly affects white individuals but has
      been reported in other ethnic groups including black individuals, Native
      Americans, and Asians. The Hispanic population is largely underrepresented in the
      epidemiology of MR. We describe 2 Hispanic patients with contrasting
      presentations of MR. Prompt recognition of MR is essential to expedite treatment
      and prevent potentially disabling sequelae of undiagnosed disease; however,
      diagnosis can be challenging due to the wide range of clinical presentations of
      MR as well as variable laboratory findings, especially in patients with skin of
      color. Our case reports underscore this phenomenon and demonstrate the importance
      of considering MR in all ethnic groups, including Hispanic patients. 

PMID- 24897137
TI  - Chlorpromazine-induced skin pigmentation with corneal and lens opacities.
AB  - Chlorpromazine is known to cause abnormal oculocutaneous pigmentation in sun
      exposed areas. We present the case of a psychiatric patient who developed blue
      gray pigmentation of the skin as well as corneal and lens opacities following 7
      years of chlorpromazine treatment. Ten months after discontinuation of
      chlorpromazine, the skin discoloration and anterior lens deposits showed partial
      improvement, but the corneal deposits remained unchanged. A review of the
      literature on the reversibility of chlorpromazine-induced abnormal oculocutaneous
      pigmentation also is provided. 

PMID- 24897138
TI  - Medical emergencies in the dermatology office: incidence and options for crisis
      preparedness.
AB  - Medical emergencies may occur in any setting, including dermatology offices. We
      examined the incidence of medical emergencies in a survey of 34 dermatologists
      northeast Ohio. Fifty-five events occurred over 565 combined years of clinical
      practice, an incidence of 1 episode every 10.3 years. We also review options for
      better preparedness for medical emergencies in dermatology practices, ranging
      from an emergency action plan for emergency personnel, basic life support (BLS)
      certification, advanced cardiac life support (ACLS) certification, and on-site
      automatic electronic defibrillators (AEDs). 

PMID- 24897139
TI  - Orofacial and digital frostbite caused by inhalant abuse.
AB  - Inhalation of volatile substances is a cheap and accessible way for individuals,
      most commonly teenagers, to ingest mind-altering substances. The adverse effects
      of using inhalants, including cardiac dysrhythmia, respiratory tract injury, and
      asphyxiation, can be devastating. Detection often is difficult, but a high degree
      of suspicion with patterns of perioral, perinasal, and/or digital lesions can
      help identify use. We report an uncommon case of severe orofacial and digital
      frostbite initially mistaken for an allergic reaction in a 20-year-old man
      following intentional inhalation of a commercial air-dusting agent containing
      1,1,1,2-tetrafluoroethane (HFC-134a). 

PMID- 24897140
TI  - Pyoderma gangrenosum following gastric bypass surgery.
AB  - Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is a rare
      complication of surgery. Its diagnosis and treatment often are delayed in the
      postsurgical setting; by the time a dermatologist is consulted, lesions often are
      quite large and may be accompanied by systemic symptoms. Prompt treatment of
      severe PG with systemic therapy is warranted; however, in patients with
      contraindications to systemic immunosuppressive agents, treatment with
      superpotent topical corticosteroids may be considered. We present a case of PG
      following gastric bypass surgery along with a review of the literature on
      postsurgical PG. 

PMID- 24897141
TI  - Bullous pemphigoid treated with intravenous immunoglobulin.
AB  - Bullous pemphigoid (BP) is a blistering autoimmune disease that primarily affects
      elderly patients who commonly present with comorbidities. Side effects from long
      term treatment with conventional cytotoxic and immunosuppressive agents may
      increase morbidity and mortality in this patient population. We present a case of
      BP in a 78-year-old woman with an active pulmonary Mycobacterium avium
      intracellulare complex (MAC) infection that precluded the use of systemic
      corticosteroids or other immunosuppressants. Our patient was successfully treated
      with intravenous immunoglobulin (IVIG) monotherapy, which may provide an
      alternative treatment option for BP patients who are unable to tolerate cytotoxic
      or immunosuppressive therapies. 

PMID- 24897142
TI  - Solitary adult myofibroma.

PMID- 24897143
TI  - What is your diagnosis? The diagnosis: leukemia cutis.

PMID- 24897144
TI  - Lichenoid photosensitivity: an unusual reaction to doxycycline and an unusual
      response.

PMID- 24897145
TI  - Generalized yellow discoloration of the skin. The diagnosis: carotenemia.

PMID- 24897146
TI  - Alopecia areata universalis complicating daclizumab therapy for uveitis.
AB  - Alopecia areata (AA) is a complication of biologic therapy with several anti
      tumor necrosis factor (TNF) inhibitors and efalizumab for the treatment of
      various autoimmune diseases. We report the case of a 51-year-old woman who
      developed AA universalis while undergoing treatment with daclizumab, an
      immunosuppressive biologic therapy, administered for treatment of inflammatory
      ocular disease. Although immunomodulatory agents that function by interfering
      with T helper cell stimulation are expected to impede autoimmune-related
      processes, we believe that daclizumab may be causally related to the development
      of AA. 

PMID- 24897147
TI  - Midodrine-induced acute generalized exanthematous pustulosis.
AB  - Acute generalized exanthematous pustulosis (AGEP) is an acute sterile pustular
      eruption most commonly induced by medications. We present a case of AGEP with
      erythroderma following use of midodrine in a 58-year-old man. Although
      antibiotics are most commonly implicated in AGEP, we emphasize that nonantibiotic
      agents also may cause AGEP, which often manifests after a longer time interval
      compared to antibiotic-associated AGEP. 

PMID- 24897148
TI  - Biologics in dermatology beyond psoriasis.
AB  - Biologic agents, or protein-based drugs derived from living cells, are becoming
      commonplace in dermatology for the treatment of psoriasis, but their use spans
      many dermatologic conditions beyond psoriasis and psoriatic arthritis. In recent
      years, there has been considerable interest in their use for other inflammatory
      skin diseases. This article will review currently available data and reports on
      the off-label use of biologics in the treatment of cutaneous diseases other than
      psoriasis, including inflammatory dermal processes, autoimmune bullous skin
      diseases, connective-tissue diseases, and hidradenitis suppurativa (HS). 

PMID- 24897149
TI  - Acantholytic anaplastic Paget disease.

PMID- 24897150
TI  - Xanthoma striatum palmare associated with nonsyndromic paucity of the
      interlobular bile ducts.

PMID- 24897151
TI  - Pruritus and hyperpigmented streaks. The diagnosis: flagellate hyperpigmentation.

PMID- 24897153
TI  - Passage order through different pathways in groups of schooling fish, and the
      diversified leadership hypothesis.
AB  - The diversified leadership hypothesis proposes that different individuals within
      a school of fish act as leaders in different circumstances. This 'circumstantial
      leadership' results from inter-individual behavioral variability and a 'cohesion
      dispersion' tendency modulated by 'failure-success' contingencies. The hypothesis
      predicts that when offered different pathways to escape the restriction of their
      swimming space, individuals within a group of fish will show Using an avoidance
      paddle and three different groups of fish (Aphyocharax erithrurus) the results
      confirmed prediction. 

PMID- 24897152
TI  - Assessment of the metabolism of therapeutic proteins and antibodies.
AB  - INTRODUCTION: In the last decade, our increased knowledge of factors governing
      the pharmacokinetics and metabolism of biologics (recombinant therapeutic
      proteins) has driven, and will continue to support, biological engineering and
      the design of delivery systems for more efficient biologics. Further research in
      analytical methods for assessing their in vitro and/or in vivo metabolism will
      also support these developments. AREAS COVERED: In this review we will discuss
      the main components affecting the metabolism of biologics, and try to demonstrate
      how novel analytical evaluations will facilitate their future development. We
      will focus on the use of radiolabeled drugs, ligand-binding assays and mass
      spectrometry. EXPERT OPINION: Future marketed biologics will be complex
      structures, such as glycoengineered, fused, or chemically modified proteins.
      Their in vivo efficiencies will be strongly dependent on their metabolic
      stabilities. Similarly to small molecular drugs, for which in vitro and in vivo
      biochemical platforms and analytical techniques have helped to rationalize
      preclinical and clinical developments, we would expect this also to translate to
      effective approaches to study the metabolism of biologics in the near future.
      Mass spectrometry should emerge as a standard technique for in vivo
      characterization of the biotransformation products of biologics.

PMID- 24897154
TI  - A preliminary examination of some effects of cocaine on within-session patterns
      of responding.
AB  - Two experiments examined within-session changes in operant responding when
      cocaine or cocaine plus food served as the reinforcer. In Experiment 1, male rats
      self-administered intravenous cocaine according to several fixed interval
      schedules. The within-session patterns of responding differed for the different
      schedules early in the session, but they converged by 50 minutes into the
      session. Because this convergence occurred regardless of the amount of cocaine
      consumed, it questions the response-stereotypy and dopamine-loading explanations
      for within-session changes in responding for cocaine reinforcers. In Experiment
      2, rats responded for sweetened condensed milk during baseline sessions. During
      experimental sessions, responding produced cocaine in addition to the condensed
      milk. The addition of cocaine altered the pattern of responding during the early
      (first 15 minutes), but not the later (last 45 minutes), parts of the session.
      These results suggest that different factors produce the early-session increases
      and late-session decreases in responding. They are also consistent with the idea
      that the early-session changes in responding represent changes in'arousal'. 

PMID- 24897155
TI  - Area marking in the ant Pheidole pallidula (Myrmicinae).
AB  - The Mediterranean dimorphic ant Pheidole pallidula has a rapid, short-lasting and
      species-specific homerange area marking. It is performed by the minor workers,
      which are stimulated to mark by the major workers. The first few minors reaching
      a new area move on it very slowly and begin to mark it by depositing spots of
      their Dufour gland content. This secretion attracts other minors and a few
      majors, which come onto the area, then return to the nest, then come back to the
      area, inviting the minors to mark the area through tactile stimulations and
      emission of their own Dufour gland content. Contrary to the minors' Dufour gland
      content, the majors' one is non-attractive and does not allow marking. After
      about ten minutes, the ants' movements on the new area become the same as that
      occurring on their usual foraging area; if not walked on any further, the area
      loses its marking within about twenty minutes. These home-range marking
      characteristics may enable the ant P. pallidula to rapidly colonize new areas and
      keep them marked for only as long as they are useful to the society. 

PMID- 24897156
TI  - The effect of olfactory and auditory stimuli on drinking suppressed with a
      conditioned taste aversion.
AB  - Two studies were conducted to assess the effect of auditory and olfactory stimuli
      on drinking that had been suppressed with a conditioned taste aversion procedure.
      Each study used a different conditioned stimulus. The first used an 8% saccharin
      solution which was readily consumed by rats, while the second used a 1% anise
      solution that was not as readily consumed by rats. The use of a relatively
      palatable conditioned stimulus and an unpalatable conditioned stimulus allows for
      an examination of any effect amount of consumption prior to conditioning might
      have. The results indicated that the stimuli increased drinking suppressed with a
      conditioned taste aversion in both studies and drinking by control rats in
      Experiment 2. In Experiment 1 the stimuli either had no effect or suppressed
      drinking in the control rats. These results indicate that low levels of drinking
      can under some circumstances, be increased via the presentation of olfactory or
      auditory stimuli. They further suggest that deflation of drinking from a high to
      a low rate is not necessary to observe this effect. 

PMID- 24897157
TI  - Removal of the olfactory system modifies male bank vole behaviour in the presence
      of females.
AB  - The role of the olfactory and vomeronasal systems of male bank voles in
      behavioural interaction with females was investigated. Bulbectomy (OBX), but not
      vomeronasalectomy (VNX), resulted in a decrease of female-stimulated ultrasonic
      calling by males, manifested as longer latency to the first call and fewer calls
      by OBX males in comparison to VNX or sham-operated (SHAM) animals. OBX males
      showed significantly fewer non-aggressive approaches but more attacks toward
      females. Females were less aggressive toward OBX males than toward VNX or SHAM
      animals, manifested as longer latency to the first attack and fewer attacks
      toward OBX males during 10 min encounters. The report may be regarded as the
      first evidence that bulbectomy of the male can evoke a behavioural reaction which
      in turn alters the activity of a female partner. 

PMID- 24897158
TI  - Rhesus monkeys fail to use gaze direction as an experimenter-given cue in an
      object-choice task.
AB  - Experiments were run to assess whether adult female rhesus monkeys would
      spontaneously learn to choose the correct (i.e. baited) of two objects on the
      basis of explicit behavioural cues given by the experimenter. In the first part
      of the study the experimenter either stood up straight with his arms by his side
      and fixated centrally between the two objects while the subject responded, or he
      engaged in various combinations of looking and pointing at the correct object.
      None of the three subjects learned to use gaze alone as a discriminative cue, but
      two performed better with gestural cues. During subsequent sessions the
      experimenter's head and eyes were positioned much closer to the objects than in
      the first experiment, but this did not significantly improve performance. These
      results confirm and extend a 'negative' finding obtained with capuchin monkeys,
      namely that during object-choice tasks monkeys do not readily use visual co
      orientation or engage in perspective-taking to enhance their success. 

PMID- 24897159
TI  - Asymmetries in the visual processing of emotional cues during agonistic
      interactions by gelada baboons.
AB  - Orientational asymmetries of male gelada baboons were assessed to determine
      visual field preferences during agonistic and post-conflict behaviour using
      photographic sequences of aggressive interactions and records of facial injuries.
      Both opponents used their left visual field significantly more frequently than
      their right during fights, threats and approaches; the degree of left visual
      field preference varied with the level of negative emotion. During post-conflict
      behaviour, only the non-retreating animal showed a significant left visual field
      preference. The observed left visual field preferences appear to indicate a right
      hemisphere dominance in the processing of emotional information. Other possible
      causes of the baboons' observed visual field preference (including processing of
      auditory cues and visuospatial information, lateralised control of the brain over
      facial expression, and the asymmetrical signalling capacity of the face) are
      discussed. 

PMID- 24897160
TI  - Lateral asymmetries during responses to novel-coloured objects in the domestic
      chick: A developmental study.
AB  - Chicks were trained to peck on a small coloured (red or green) box for food
      reinforcement. They were then presented with one box identical to that used
      during training (familiar) and one of a different colour (unfamiliar). Food
      reinforcement was delivered for pecking either box, and the right-left position
      of the two boxes was alternated at random between trials. The number of times
      chicks pecked at the novel box when it was located on their right or on their
      left side was recorded. Chicks showed a general tendency to peck more frequently
      at the novel box when it was located on their right side. The lateral asymmetry
      was, however, age-dependent. Maximum lateral bias with both red and green novel
      boxes was observed at around day 4 and day 11 in both sexes, and minimum at
      around days 7 8 in males and days 8 9 in females. It is suggested that these
      lateral asymmetries can be accounted for in terms of a head-and-body turning bias
      associated to preferential use of the lateral field of vision of the left eye,
      which arises from specializations of the contralateral brain structures (i.e.
      right hemisphere involvement in response to novelty). The observed changes in
      lateral asymmetries during development appear, in fact, to fit very well with
      independent behavioural and pharmacological evidence for biases to left eye use
      on day 11, and right eye use on day 8. 

PMID- 24897161
TI  - Exposure to the social interaction test in rats induces changes in defensive
      burying.
AB  - To detect changes in experimental anxiety, defensive burying (DB) was studied in
      several groups of rats after being exposed to social interaction (SI). Animals
      were studied in the DB paradigm after being submitted to the following SI
      treatments: control (without SI exposure), and SI for 1.5, 5, 10 and 15 min
      respectively. A bimodal effect was found: facilitated DB response values in the
      group tested after a 1.5 min exposure to SI and a strong reduction of DB in the
      10 and 15 min groups. The inhibition in DB elicited by the 15 min exposure to SI
      revealed a slow recovery, returning to control levels after 30 min. The actions
      of novelty on defensive burying were assessed in a third experiment. Animals were
      tested for DB immediately after being placed for 1.5 or 15 min in the SI arena
      without a partner. DB levels increased in these animals. Another group was placed
      in the SI arena for 1.5 min and tested in the DB paradigm 13.5 min after being
      returned to the home cage. A return to the basal control DB levels was observed
      in this group. Data are discussed in terms of anxiety-like fluctuations and the
      adaptive functions underlying these. 

PMID- 24897162
TI  - Male reproductive success in the domestic cat (Felis catus L.): A case history.
AB  - The domestic cat shows a great variability in different life history traits like
      its social organization, ranging from a solitary life to living in large social
      groups depending on environmental conditions. Until now, the mating system has
      not been shown to vary between populations and was described as promiscuous. Here
      we present data on the reproductive success of a male, which clearly show that
      monopolization of females by males is possible in this species. 

PMID- 24897163
TI  - Protein-DNA chimeras for nano assembly.
AB  - In synthetic biology, "understanding by building" requires exquisite control of
      the molecular constituents and their spatial organization. Site-specific coupling
      of DNA to proteins allows arrangement of different protein functionalities with
      emergent properties by self-assembly on origami-like DNA scaffolds or by direct
      assembly via Single-Molecule Cut & Paste (SMC&P). Here, we employed the ybbR
      tag/Sfp system to covalently attach Coenzyme A-modified DNA to GFP and, as a
      proof of principle, arranged the chimera in different patterns by SMC&P.
      Fluorescence recordings of individual molecules proved that the proteins remained
      folded and fully functional throughout the assembly process. The high coupling
      efficiency and specificity as well as the negligible size (11 amino acids) of the
      ybbR-tag represent a mild, yet versatile, general and robust way of adding a
      freely programmable and highly selective attachment site to virtually any protein
      of interest. 

PMID- 24897165
TI  - Clinical and mucosal improvement with specific carbohydrate diet in pediatric
      Crohn disease.
AB  - OBJECTIVE: The aim of the study was to prospectively evaluate clinical and
      mucosal responses to the specific carbohydrate diet (SCD) in children with Crohn
      disease (CD). METHODS: Eligible patients with active CD (Pediatric Crohn's
      Disease Activity Index [PCDAI] >= 15) underwent a patency capsule and, if passed
      intact, capsule endoscopy (CE) was performed. Patients taking SCD were monitored
      for 52 weeks while maintaining all prescribed medications. Demographic, dietary,
      and clinical information, PCDAI, Harvey-Bradshaw Index (HBI), and Lewis score
      (LS) were collected at 0, 12, and 52 weeks. CEs were evaluated by an experienced
      reader blinded to patient clinical information and timing. RESULTS: Sixteen
      patients were screened; 10 enrolled; and 9 completed the initial 12-week trial
      receiving 85% of estimated caloric needs before, and 101% on the SCD. HB
      significantly decreased from 3.3 +/- 2.0 to 0.6 +/- 1.3 (P = 0.007) as did PCDAI
      (21.1 +/- 5.9 to 7.8 +/- 7.1, P = 0.011). LS declined significantly from 2153 +/-
      732 to 960  +/- 433 (P = 0.012). Seven patients continued the SCD up to 52 weeks;
      HB (0.1 +/- 0.4) and PCDAI (5.4 +/- 5.5) remained improved (P = 0.016 and 0.027
      compared to baseline), with mean LS at 1046 +/- 372 and 2 patients showed
      sustained mucosal healing. CONCLUSIONS: Clinical and mucosal improvements were
      seen in children with CD, who used SCD for 12 and 52 weeks. In addition, CE can
      monitor mucosal improvement in treatment trials for pediatric CD. Further studies
      are critically needed to understand the mechanisms underlying SCD's effectiveness
      in children with CD.

PMID- 24897164
TI  - Health-related quality of life over time in children with eosinophilic
      esophagitis and their families.
AB  - OBJECTIVES: Existing treatments for pediatric eosinophilic esophagitis (EoE)
      effectively reduce inflammation. The impact of treatment on health-related
      quality of life (HRQoL) over time for pediatric patients with EoE and their
      families, however, has not been systematically assessed. We hypothesized that
      individualized multidisciplinary treatment would improve both child and family
      HRQoL over time, with improvements associated with decreased symptom severity.
      METHODS: Children with EoE treated in 4 tertiary care centers were enrolled.
      Baseline assessments occurred at the time of patients' first evaluation; follow
      up assessments occurred at 2 and 6 months after baseline. Presence and severity
      of 8 EoE symptoms were measured. HRQoL was measured with the Pediatric Quality of
      Life Inventory parent proxy report, child self-report (CR), and Family Impact
      Module (FIM). Statistical analyses used mixed-effects modeling to test changes
      over time for child and family HRQoL. RESULTS: Ninety-seven children were
      enrolled (ages 2-18 years, mean age 7.7 years +/- 4.8, 78% boys, 80% white).
      Baseline mean symptom number was 3.5 (standard deviation 2.3), and symptom
      severity was 5.5 (standard deviation, 4.5). HRQoL scores were significantly
      related to symptom scores (P < 0.001). EoE symptom severity decreased during the
      study (P = 0.03). Pediatric Quality of Life Inventory parent proxy Total and FIM
      Total scores improved from baseline to 6 months (respectively, adjusted means
      78.4 vs 81.0, P = 0.0006; 68.9 vs 70.1, P = 0.03). Interactions with baseline
      symptom severity revealed that subjects with lowest symptom severity showed the
      most improved HRQoL scores (P = 0.0013). CONCLUSIONS: HRQoL improved during the
      course of evaluation and treatment, with positive changes being strongest for
      patients with less symptom severity at baseline.

PMID- 24897166
TI  - Markers of inflammation in the breath in paediatric inflammatory bowel disease.
AB  - OBJECTIVES: Breath analysis and exhaled breath condensate (EBC) collection are
      simple and noninvasive processes whereby inflammatory mediators and other
      biomarkers can be assessed in diseases that affect the lung. It was hypothesised
      that markers of epithelial dysfunction and secretion, such as a low pH, 8
      isoprostane, and release of epithelial factors such as trefoil factor 2 (TFF2)
      and mucin, would be elevated in the breath of those with inflammatory bowel
      disease (IBD). The aim was to compare the levels of these biomarkers in EBC and
      the fraction of expired nitric oxide (FENO) in children with Crohn disease (CD),
      in those with asthma, and in normal individuals in a pilot study. METHODS: EBC
      was collected from patients in the 3 groups mentioned above in a cross-sectional
      design. pH, 8-isoprostane, TFF2, and mucin levels were measured in the EBC.
      Spirometry was performed in asthmatic patients and patients with IBD, whereas
      FENO and skin prick tests were performed in patients with IBD. RESULTS: Breath
      samples including EBC were collected from 80 patients (30 CD, 30 asthma, 20
      controls). Compared with controls, EBC pH was lower in children with IBD (P <
      0.0001) or asthma (P = 0.0041). 8-Isoprostane levels differed between the 3
      groups (P < 0.05). EBC TFF2 was mainly less than the limit of detection, whereas
      mucin levels did not differ significantly between the 3 groups. FENO was
      measurable in children with IBD, but did not correlate with disease activity or
      serum markers of inflammation. CONCLUSIONS: A lower EBC pH may reflect
      inflammatory events either in the lung or systemically. 8-Isoprostane, FENO, and
      mucin were detected for the first time in the EBC of children with IBD. Further
      studies are required to assess the value of these assessments.

PMID- 24897167
TI  - Liver involvement in the Hispanic population of North America with cystic
      fibrosis.
AB  - OBJECTIVES: The aim of the present article was to determine the prevalence of
      liver involvement in Hispanic patients with cystic fibrosis (CF) and identify
      associations with age and severity of liver involvement. METHODS: We used 1994
      2005 Epidemiologic Study of CF data to compare abnormal liver findings between
      Hispanic and non-Hispanic white patients with CF. RESULTS: Of 30,727 patients
      with CF, 5015 had liver involvement. Of 1957 Hispanic patients, 20.8% had liver
      involvement compared with 16.0% of 28,770 non-Hispanic white patients (odds ratio
      [OR] 1.38, 95% confidence interval [CI] 1.23-1.54). This higher prevalence of
      liver involvement persisted after adjusting for demographics and meconium ileus
      and was especially high in the first year of life (adjusted OR 3.14, 95% CI 2.27
      4.35). Ten percent of infants with only elevated liver enzymes progressed to more
      severe liver disease. CONCLUSIONS: The Hispanic population with CF has more liver
      involvement (both elevated liver enzymes and clinical liver disease) than the non
      Hispanic white population with CF, especially during the first year of life.

PMID- 24897168
TI  - IBS and FAPS in children: a comparison of psychological and clinical
      characteristics.
AB  - OBJECTIVES: It has been suggested that different subcategories of childhood
      abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) are not
      separate clinical entities, but represent variable expressions of the same FGID.
      The aim of the present study was to compare clinical and psychological
      characteristics of children with irritable bowel syndrome (IBS), functional
      abdominal pain (FAP), and functional abdominal pain syndrome (FAPS). METHODS: A
      total of 259 children, ages 8 to 18 years, fulfilling Rome III criteria for IBS
      or FAPS were included in a randomized controlled trial evaluating the effect of
      hypnotherapy. At inclusion, questionnaires assessed demographics, clinical
      features, abdominal pain frequency and intensity, depression and anxiety,
      somatization, health-related quality of life, pain beliefs, and coping
      strategies. RESULTS: No differences were found between children with IBS and
      those with FAPS with respect to the main outcomes: frequency and intensity of
      abdominal pain, symptoms of depression and anxiety, somatization, health-related
      quality of life, pain beliefs, and coping strategies. A significantly higher
      percentage of patients with IBS had a positive family history for AP-FGIDs (56.8%
      vs 37.8%; P = 0.00). Characteristics of patients with IBS subtypes did not
      differ. Patients with FAP or FAPS differed only with respect to problem-focused
      coping strategy (2.21 +/- 0.61 vs 2.52 +/- 0.49; P = 0.00). CONCLUSIONS:
      Pediatric patients with IBS and those with FAPS have similar psychosocial
      profiles. These results may explain why treatment response of psychological
      therapies in these AP-FGIDs is similar. These results may indicate that pediatric
      IBS and FAPS are different expressions of 1 underlying functional disorder, but
      similarities in psychosocial characteristics do not exclude the possibility that
      these disorders are different entities, because these similarities can exist
      between disorders of various causes. Therefore, future research is required on
      the role of other (physiological) factors in pediatric IBS and FAPS.

PMID- 24897169
TI  - Bowel preparation for pediatric colonoscopy: report of the NASPGHAN endoscopy and
      procedures committee.
AB  - Pediatric bowel preparation protocols used before colonoscopy vary greatly, with
      no identified standard practice. The present clinical report reviews the evidence
      for several bowel preparations in children and reports on their use among North
      American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
      members. Publications in the pediatric literature for bowel preparation regimens
      are described, including mechanisms of action, efficacy and ease of use, and
      pediatric studies. A survey distributed to pediatric gastroenterology programs
      across the country reviews present national practice, and cleanout
      recommendations are provided. Finally, further areas for research are identified.

PMID- 24897170
TI  - Impact of snacking pattern on overweight and obesity risk in a cohort of 11- to
      13-year-old adolescents.
AB  - OBJECTIVES: The association between snacking habits and overweight in adolescents
      is unclear. We evaluated the relation between snacking patterns and
      overweight/obesity in a cohort of 11- to 13-year-old Italian adolescents.
      METHODS: The dietary habits of 400 randomly selected adolescents were evaluated;
      those with body mass index >= 85 th percentile were considered as
      overweight/obese. Participants were classified based on the percentage of caloric
      intake from snacks (<15%, 15%-20%, >20%), snacking frequency (1, 2, >= 3), and
      timing of consuming the most caloric snack (morning, afternoon, evening).
      RESULTS: A minority of participants (13/400, 3.3%) did not consume any snacks;
      5/13 (38.5) of them were overweight/obese. Among snackers (387/400),
      overweight/obesity prevalence was 10.4%, 14.4%, 20.5%, respectively, in those
      consuming <15%, 15% to 10%, and >20% of their energy intake from snacks. In a
      Poisson regression model, the overweight/obesity relative risks (RRs) were 1.35
      (95% confidence interval [CI] 0.58-3.15) and 2.32 (1.10-4.89) for 15% to 20% and
      >20% calories/day from snacks, respectively. Overweight/obesity prevalence (from
      9.6% to 22.6%) was correlated with snacking frequency (RR 2.20, 95% CI 0.92-5.27,
      and RR 4.17, 95% CI 1.60-10.9, for 2 and >= 3 snacks per day, respectively). The
      most caloric snacks were consumed in the morning (180/387) and afternoon
      (179/387); 28.6% of the predominantly evening snackers (28/387) were
      overweight/obese (RR 3.12, 95% CI 1.17-8.34). CONCLUSIONS: Increased snacking
      calories, frequency, and evening snacking are independently associated with
      overweight/obesity in Italian middle-school adolescents.

PMID- 24897171
TI  - Selenoprotein S is involved in maintenance and transport of multiprotein
      complexes.
AB  - SelS (Selenoprotein S) is a selenocysteine-containing protein with roles in ER
      (endoplasmic reticulum) function and inflammation. It has been implicated in ERAD
      (ER-associated protein degradation), and clinical studies revealed an association
      of its promoter polymorphism with cytokine levels and human diseases. However,
      the pathways and interacting proteins that could shed light on pathogenesis of
      SelS-associated diseases have not been studied systematically. We performed a
      large-scale affinity isolation of human SelS and its mutant forms and analysed
      the proteins that interact with them. All previously known SelS targets and
      nearly two hundred additional proteins were identified that were remarkably
      enriched for various multiprotein complexes. Subsequent chemical cross-linking
      experiments identified the specific interacting sites in SelS and its several
      targets. Most of these interactions involved coiled-coil domains. The data
      suggest that SelS participates in intracellular membrane transport and
      maintenance of protein complexes by anchoring them to the ER membrane. 

PMID- 24897172
TI  - Initiation of rod outer segment disc formation requires RDS.
AB  - Rod outer segment (OS) morphogenesis involves assembly of flattened discs
      circumscribed by a hairpin-like rim, however, the role of the rim and rim
      proteins such as retinal degeneration slow (RDS) and its homologue rod OS
      membrane protein-1 (ROM-1) in this process remains unclear. Here we show that
      without RDS, no disc/OS formation occurs, while without rhodopsin, small OS
      structures form containing aligned nascent discs. In the absence of both
      rhodopsin and RDS, RDS-associated degeneration is slowed, and ROM-1 is stabilized
      and trafficked to the OS. These animals (rho-/-/rds-/-) exhibit OSs slightly
      better than those lacking only RDS, but still without signs of disc formation.
      These results clearly demonstrate that OS morphogenesis is initiated by RDS
      mediated rim formation, a process ROM-1 cannot recapitulate, with subsequent disc
      growth mediated by rhodopsin. The critical role of RDS in this process helps
      explain why photoreceptors are so sensitive to varied RDS levels, and why
      mutations in RDS cause debilitating retinal disease. 

PMID- 24897173
TI  - Preventing infective complications following leech therapy: elimination of
      symbiotic Aeromonas spp. from the intestine of Hirudo verbana using antibiotic
      feeding.
AB  - BACKGROUND: Hirudotherapy is often used successfully in modern medicine,
      especially in plastic and reconstructive surgery. However, Aeromonas infections
      are the most common complications of post-operative leech application. Hence,
      prophylactic antibiotic administration is recommended before and during leech
      therapy. It has been confirmed that patient safety and achieving the desired
      therapeutic effect depend mainly on the microbiologic purity of the animals used.
      The aims of this study were to find a safe and practical way to eradicate
      symbiotic Aeromonas spp. occuring in the intestine of Hirudo verbana. METHODS:
      Leeches were fed artificially with 1.5 mL of sterile defibrinated sheep blood
      supplemented with ciprofloxacin (CIP) or cefotaxime (CTX), at bacteriostatic
      concentrations of 0.2 mcg/mL or 1.5 mcg/mL, and bactericidal concentrations of 20
      mcg/mL or 50 mcg/mL, respectively. Bacteria were isolated from the leech
      intestines before and after feeding at different time intervals: 1, 7, 14, 21,
      and 28 d. RESULTS: Biochemical identification of bacterial isolates from water
      samples and intestines of H. verbana using the API-NE20 test showed that A.
      veronii biovar sobria was predominant. Bacteria belonging to the genus Aeromonas
      were detected in all control leeches. The results showed that optimum eradication
      of bacteria from leech intestines was obtained using 20 mcg/mL of CIP and 50
      mcg/mL of CTX, which decreased the number of Aeromonas spp. to undetectable
      levels for two weeks after feeding in all treated leeches. A statistically
      significant reduction in the number of bacterial colonies (p<0.0001) was observed
      in leeches treated with bacteriostatic concentrations of CIP or CTX; no bacterial
      growth was found on the plates after only seven days of feeding with antibiotics.
      All water samples in which the leeches were kept before treatment were
      contaminated with Aeromonas spp., whereas these samples were negative after
      antibiotic feeding of animals. CONCLUSIONS: All leeches were ready to take a
      blood meal after treatment, suggesting the possibility of using ciprofloxacin
      treated or cefotaxime-treated leeches instead of chemoprophylaxis in patients
      undergoing hirudotherapy.

PMID- 24897175
TI  - Sleep postures and power spectrum analysis of the EEG of the rat.
AB  - An analysis of the relation between sleep postures and EEG power spectrum of
      young, adult and old male rats was performed. Three postures were distinguished:
      stretched, curved and curled up. A 5 minutes period of any posture was analyzed.
      The sleep data were gathered of the first two hours of the sleep period. The
      analysis revealed that the overall power of a curled up posture was less than
      that of two other sleep postures. Determination of a relation between an EEG
      measurement and sleep postures is promising. 

PMID- 24897174
TI  - Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and
      risk of childhood brain tumors.
AB  - Childhood brain tumors (CBT) are the second most common childhood cancers, yet
      their etiology is largely unknown. We investigated whether maternal gestational
      intake of folate and vitamins B6 and B12 was associated with CBT risk in a
      nationwide case-control study conducted 2005-2010. Case children 0-14 years were
      recruited from all 10 Australian pediatric oncology centers. Control children
      were recruited by national random digit dialing, frequency matched to cases on
      age, sex, and state of residence. Dietary intake was ascertained using food
      frequency questionnaires and adjusted for total energy intake. Data from 293 case
      and 726 control mothers were analyzed using unconditional logistic regression.
      The odds ratio (OR) for the highest versus lowest tertile of folate intake was
      0.70 [95% confidence interval (CI): 0.48, 1.02]. The ORs appeared lower in
      mothers who drank alcohol during pregnancy (OR = 0.45, 95% CI: 0.22, 0.93),
      mothers who took folic acid (OR = 0.67, 95% CI: 0.42, 1.06) or B6/B12 supplements
      (OR = 0.51, 95% CI: 0.25, 1.06) and in children younger than 5 years (OR = 0.50,
      95% CI: 0.27, 0.93). These findings are consistent with folate's crucial role in
      maintenance of genomic integrity and DNA methylation. Dietary intake of B6 and
      B12 was not associated with risk of CBT.

PMID- 24897176
TI  - The importance of the temporal pattern of syllables and the syllable structure of
      display calls for individual recognition in the genus aptenodytes.
AB  - Aptenodytes penguins have a recognition call consisting of a series of repeated
      syllables. Play-back experiments were conducted to determine the respective
      importance of the temporal pattern of syllables and the syllable structure. Two
      hybrid signals were created by switching the temporal pattern of the familiar
      call (partner or parent) with that of an alien call, then played back to relevant
      partners. The hybrid signal with the familiar temporal pattern of syllables and
      an alien syllable structure induced no response of individual recognition, while
      the hybrid signal with an alien temporal pattern of syllables and the familiar
      syllable structure elicited some positive responses. 

PMID- 24897177
TI  - [Not Available].
AB  - Visually guided orientation is studied during ontogeny in field crickets (Gryllus
      bimaculatus) bred into complete darkness from egg stage. It is compared to
      control animals bred in normal 12L 12D light cycle conditions. Control animals
      are strongly scototactic: whatever their age, 85% of them step towards low
      reflecting targets. On the contrary, for the experimental group (visually
      deprived), only 20% of the first larval instar crickets orientate towards
      vertical black stripes on a white background. A frame by frame analysis of video
      recordings allows to measure more accurate parameters of the orientation trails.
      Results show that experimental animals, already at the fifth larval instar, are
      able to orientate towards the targets as many as the control ones, nevertheless,
      they still present strong, permanent impairments of exploratory behaviour and
      visual fixation. 

PMID- 24897178
TI  - Within-session responding as a function of post-session feedings.
AB  - Ten rats pressed levers or keys for food reinforcers delivered by a multiple
      variable interval schedule. The delay between the end of the session and the
      delivery of a post-session feeding varied from 0 to 240 minutes. Contrary to the
      results reported by Bacotti (1976), response rates were not significantly higher
      when post-session feedings were delayed than when they were immediate. Response
      rates also increased and then decreased within the session, regardless of the
      delay to post-session feedings. These results suggest that subjects do not always
      integrate rewards across locations. Therefore, theories need not always include
      the temporal location of post-session feedings in the context of variables that
      determines responding within the session. Experiments must also take care to
      ensure that changes in response rates within the session do not confound the
      interpretation of their results. 

PMID- 24897179
TI  - Effects of changes in brood composition of the activities of three associated
      foundresses of the paper wasp Polistes dominulus (Christ).
AB  - In this study, the effects of changes in brood composition on the activities of
      the associated females are investigated in three-foundress nests during the pre
      emergence period. Partial correlation coefficients were computed between four
      variables describing the brood composition (number of eggs, small larvae, large
      larvae, and pupae) and the duration of nineteen behavioural items performed by
      the foundresses. Alpha females were found to frequent the face of the comb when
      there was a large number of eggs. Once the larvae had hatched, these females
      participated only in activities taking place on the nest. Apart from periods of
      cell initiation, Alpha females left the nest only in order to rest. Beta females
      were generally very active, and their activity level was not sensitive to changes
      in the brood composition. Gamma females showed a lower activity level which was
      easily stimulated by changes in the brood. These females seem to start working
      when Beta activity no longer suffices to meet the needs of the colony. 

PMID- 24897180
TI  - Rule induction from examples for expert systems in mouse behavior.
AB  - Quinlan's ID3 algorithm has been used to induce, from behavioral sequences
      observed on mice in day and night conditions, rules linking each activity to the
      three preceding ones in a given sequence. These rules were then input into two
      expert systems so that they might be validated on other behavioral sequences. It
      is shown that the succession of various activities exhibited by the mouse is by
      no means random, but rather displays a Markovian determinism of the first order
      during the night and of the second order during the day. Among the seven
      activities singled out in this study, the method applied here has proven very
      effective in predicting the occurence of rest, locomotion, and grooming in the
      nest. It is only moderately effective in the cases of feeding and nest-building
      and fails with respect to drinking and to grooming out of the nest. These results
      are discussed in the light of current knowledge about the physiological
      determinants of these various activities. Lastly, the method employed here is
      compared with other methods having similar uses. 

PMID- 24897181
TI  - Learning to gain access to a foraging and dustbathing substrate by domestic fowl:
      is 'out of sight out of mind'?
AB  - Domestic fowl were deprived of the opportunity to perform litter-related
      behaviour for three or four days and were tested in a Y-maze (which they had
      previously been trained to run) for their ability to associate a coloured cue
      with gaining access to peat. When the goal boxes were within sight of the choice
      point, most birds chose peat. However, when the birds had to rely solely on the
      coloured cue only one bird from 12 showed learning. However, the birds seemed to
      have some expectation of a reward, as they ran faster if, on the previous trial,
      they had chosen peat. The inability of the birds to learn the association may
      have been an artefact of the schedule of deprivation and testing, for when they
      were hungry and tested in the same way they were again unable to learn an
      association between the same coloured cue and food reward. The experiment with
      peat was repeated using "massed" trials (several trials in immediate succession)
      during training and testing and six from 15 birds showed learning. These results
      suggest that the initial failure to learn was probably due to the training and
      testing schedule, that access to peat appears to be rewarding and that hens can
      learn an association between an abstract cue and a rewarding consequence. This is
      consistent with the possibility that domestic fowls may have some cognitive
      representation of peat when it is out of sight. 

PMID- 24897182
TI  - Relationship between the sexual performance of bulls and their behavioral
      responses to non-sexual novel stimuli.
AB  - Individual differences in the sexual reaction times and ejaculation rates
      (serving capacity) of 14 beef bulls were compared with their behavioral responses
      to a novel arena and to novel non-sexual visual and auditory stimuli. Correlation
      coefficients for ejaculation rates were consistently low and nonsignificant, but
      bulls that were most inhibited by the novel environment/stimuli exhibited the
      longest latencies for first mount and ejaculation. The emotional reactivity of
      bulls may be more closely related to their sexual inhibitions than to measures of
      reproductive success. 

PMID- 24897183
TI  - An analysis of movements of the wood mouse Apodemus sylvaticus in its home range.
AB  - The aim of this study was to quantify the movements of the wood mouse Apodemus
      sylvaticus in its home range. The movements were recorded using a new tracking
      method: it consisted of tracking a visually tagged wood mouse by a telescope from
      an observation tower and automatically recording the successive positions of this
      telescope (corresponding to the successive positions of the wood mouse in the
      field). Statistical analysis of 51 recorded movements, involving 10 wood mice,
      was carried out. The characteristics of the general movement patterns fitted a
      first order correlated random walk model. Furthermore, the detailed structure of
      paths was quantified. An analysis of variance showed that an individual factor
      was involved in metric and temporal movement characteristics but not in the
      statistical structure of the paths. Lastly, examination of all the movements of 6
      wood mice, with for which at least 4 different paths were recorded, revealed
      their space use patterns within their home ranges. 

PMID- 24897184
TI  - Effect of earth as an additional stimulus on the behaviour of confined piglets.
AB  - Groups of 8 piglets were housed in flat-deck cages with slatted floors.
      Experimental cages were provided with a trough of sterilized earth, and the
      behaviour of focal individuals was recorded for comparison with controls. This
      replaced an earlier study, with which some of the results were combined. Records
      were analysed for frequencies and duration of certain activities, and first order
      sequence analysis was carried out. Experimental piglets rooted in earth for 4 to
      8% of observations and also fed for longer. They spent less time sitting or
      lying. Aggression was reduced and there was a trend for experimental piglets to
      chew each other less. These differences suggested conditions were more favourable
      in experimental pens than control pens. However, there were few differences in
      first order behavioural transitions. Use of earth was not involved in sequences
      with activities such as feeding, drinking or lying as expected. It seems likely
      that in these circumstances earth did not act as a stimulus relevant to
      behavioural organization, but in some other way, with interest declining over
      time. 

PMID- 24897185
TI  - An analysis of mother-young behaviour of fallow deer during lactation period.
AB  - In the Donana National Park (SW Spain) female fallow deer (Dama dama ) give birth
      during the first fortnight of June, the next breeding season starting at the
      beginning of October. Between these two events the most important part of
      lactation takes place. Daily observations were made during the summer of 1984 and
      1985. The population studied was made up of fourteen mother-young pairs that we
      were able to recognize individually. During each sampling period a pair of mother
      young was scanned. Activities were categorized as follows: feeding, walking,
      selfgrooming, vigilance, mother-young interactions, and social interactions. No
      differences were observed in the ontogeny of behaviour neither between male and
      female fawns nor between their mothers. However, analysing individual differences
      there appeared a variation between mothers in relation to the rate of
      interactions towards their fawns, which was in positive correlation with the
      fawn's weight in the case of males. Our results also suggest the possibility of
      higher investment in heavier female fawns. Furthermore, there is an annual
      variation in the maternal behaviour in relation to the availability of resources.

PMID- 24897186
TI  - Changes in cuticular hydrocarbon composition in relation to age and sexual
      behavior in the female Calliphora Vomitoria (Diptera).
AB  - Qualitative and quantitative changes in epicuticular hydrocarbon
      synthesis/release were observed during the first gonadotrophic cycle of
      Calliphora vomitoria. Up to 12 hours after eclosion, hydrocarbon
      synthesis/release is low, with little change in the relative proportions of the
      compounds detected. At 24 hours there is a marked increase in hydrocarbon
      synthesis/release, especially in the monomethylalkanes (both absolute and
      relative amounts). Between 48 and 72 hours, hydrocarbon synthesis stabilizes. At
      83 hours, two hydrocarbon patterns can be distinguished, depending on the state
      of receptiveness of the females. The results show for the first time that
      differences in age, sexual attractiveness and receptivity are accompanied by
      characteristic changes in cuticular n-alkanes and mono-methylalkanes. 

PMID- 24897187
TI  - Transformation of a waiting schedule into a temporal regulation schedule (DRRD)
      by addition of external stimuli in the dog.
AB  - Waiting schedules do not impose temporal regulation but condition the animal to
      give the operant response during a given time. At the end of the required delay,
      a positive discriminative stimulus is presented. The suspension of the response
      while the discriminative stimulus is being given suspension of the response while
      the discriminative stimulus is being given is accompanied by reinforcement. The
      transformation of a waiting schedule into a temporal regulation schedule is
      generally achieved by suppressing the external facilitating factors or by
      physically modifying them. Our study reveals that a similar transformation can be
      achieved in the dog by the addition of a further stimulus. This stimulus, which
      is physically exactly the same as the excitatory stimulus and which punctuates
      the waiting period, is randomly introduced into the temporal delay. The absence
      of reinforcement in response to the added stimulus should force the animal to
      regulate its behavior in time and the additional negative discriminative stimulus
      favours the expression of the active nature of the inhibation. The results show
      that subjects can differentiate their response durations according to stimuli
      that only differ according to temporal location. Thus this pattern resembles a
      DRRD schedule. The peak of responses at the time of the inhibition stimulus
      reveals considerable behavioral conflict : either the response must be maintained
      or the inhibition suppressed. The positive or negative resolution of this
      conflict reveals noteworthy aspects of the behavioural inhibition process. 

PMID- 24897188
TI  - Choice of perch by the water stick insect.
AB  - Several characteristics of an adequate perch site for the water stick insect,
      Ranatra linearis L. (Heteroptera: Nepidae) and variations of perch preference
      during post-embryonic development have been investigated. Under laboratory
      conditions adults preferred reeds (Calamagrostis epigeros and Phragmites communis
      ) to the other plant species presented and avoided rushes (Juncus sp.). These
      results confirmed Waitzbauer's (1976) observations that showed that Ranatra
      preferred Phragmites communis over Utricularia vulgaris in the field. During
      development, preference for one type of plant changed first from Lemna to Elodea
      , then after the 4th instar, from Elodea to reeds. Predator size in relation, to
      perch size did not appear to be the main factor influencing these changes of
      preference. Perch colour preference changed during development from green to
      brown. In addition, adults preferred vertical perches to horizontal ones, but
      approximately as many 1st and 2nd instar larvae were found on vertical perches as
      on horizontal ones. Renatra usually perched parallel to their support: in the
      majority of observations the longitudinal axis of the body formed an angle of
      between - 5 degrees  and + 15 degrees  with the vertical plane at all
      developmental stages. 

PMID- 24897189
TI  - Detection of low dose effects of psychopharmaca: Application of a semi-Marcov
      model to rhesus monkey behaviour.
AB  - Behavioural testing of psycho-active drugs at lower doses is needed for medical
      applications and for the study of pharmacological brain mechanisms. Sensitive
      methods to detect effects on the time structure of behaviour are lacking. We
      propose a procedure based on a description within the framework of continuous
      time Marcov chain models. This class of models is generalized to account for
      constraints on the organisation of a motor pattern including the speed at which
      it is terminated. This leads to semi-Marcov models with transition rates that
      quickly increase from zero to a constant level. We describe and compare several
      models. As an application we consider amphetamine effects on infant rhesus
      monkeys. One of the models is preferred since, besides giving a good fit, it
      demonstrates consistent amphetamine effects that can be interpreted as short-term
      effects on motor constraints. Amphitamine also induced more mother-directed
      behaviour. We give maximum likelihood procedures for behaviour analysis based on
      the preferred model. 

PMID- 24897190
TI  - Stimulus class formation and functional equivalence in moderately retarded
      individuals' conditional discrimination.
AB  - Three mentally retarded humans first acquired a simple discrimination:
      Simultaneously displayed visual stimuli A1 and A2 functioned as S+ and S-,
      respectively. The subjects also acquired a conditional discrimination, learning
      to select visual stimuli B1 and B2 conditionally upon A1 and A2, respectively.
      Then, B1 and B2 were displayed without A1 or A2. Subjects selected B1, an
      emergent discrimination that showed that B1 and B2 had become functionally
      equivalent to A1 and A2, respectively. Two subjects next learned to select C1 and
      C2 conditionally upon B1 and B2, respectively. They also learned to select B1 and
      B2 conditionally upon D1 and D2, respectively. Subsequent simple discrimination
      probe trials displayed (a) C1 and C2 and (b) D1 and D2. On the former, the
      subjects nearly always selected C1. On the latter, they initially selected D1 and
      D2 about equally often. Thus, the emergence of simple discrimination appears to
      depend on a specific experimental history. 

PMID- 24897191
TI  - A novel smart microsphere with magnetic core and ion-recognizable shell for Pb2+
      adsorption and separation.
AB  - Smart core-shell microspheres for selective Pb(2+) adsorption and separation have
      been developed. Each microsphere is composed of a Pb(2+) recognizable poly(N
      isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNB) shell and a magnetic
      Fe3O4 core. The magnetic PNB core-shell microspheres show excellent Pb(2+)
      adsorption selectivity among the coexisting Cd(2+), Co(2+), Cr(3+), Cu(2+),
      Ni(2+), Zn(2+), K(+), and Ca(2+) ions by forming stable B18C6Am/Pb(2+) host-guest
      complexes and exhibit an interesting temperature-dependent Pb(2+) adsorption. The
      inner independent magnetic Fe3O4 cores enable the Pb(2+)-adsorbed microspheres
      with a magnetically guided aggregation to be separated from the treated solution
      using a remotely controlled manner. The isothermal Pb(2+) adsorption result fits
      well with the Freundlich isotherm. The magnetic PNB core-shell microspheres show
      very fast adsorption of Pb(2+), and the adsorption process of Pb(2+) onto
      magnetic PNB core-shell microspheres fits well with the pseudo-second-order
      model. Moreover, Pb(2+)-adsorbed microspheres can be regenerated by simply
      increasing the operation temperature and washing with deionized water. The
      proposed magnetic PNB core-shell microspheres provide a promising candidate for
      Pb(2+) adsorbents with selectively separable and efficiently reusable abilities. 

PMID- 24897192
TI  - Second-order discrimination in humans: the roles of explicit instructions and
      constructed verbal responding.
AB  - In two experiments, university students were trained on a conditional
      discrimination task (second-order matching to sample) involving various types of
      stimulus presentations and experimenter-provided instructions. The students'
      acquisition of conceptual behavior was assessed during transfer tests defined at
      the intramodal, extramodal and extrarelational levels. On each transfer trial,
      subjects had to construct their own verbal description of the stimulus being
      chosen and of the stimulus relation controlling their current choice. The main
      finding was that conceptual behavior during test trials developed largely
      independently of the training conditions. The acquisition of conceptual behavior
      in these experiments may be attributed to the subjects' constructing their own
      verbal descriptions on each transfer trial. These findings are discussed in
      relation with the notions of problem solving, generalized responding, and rule
      governance. 

PMID- 24897194
TI  - Conditional discrimination: the role of CS-alone trials.
AB  - Two experiments examined the role of CS-alone trials in the acquisition of a
      serial feature positive and negative conditional discrimination. In Experiment 1
      the acquisition of an 'ambiguous target' discrimination in which a single target
      cue was reinforced on some trials and nonreinforced on others (P->T+; N->T-) was
      examined with various sorts of additional target alone training (T+; T-; T+T-;
      T0). Experiment 2 examined the effects of the same kinds of additional target
      training trials on the performance of discriminations in which different target
      cues were presented after the positive feature (P->W+, N->T- trials for group
      with T+ alone trials) and after negative feature (P->T+, N->W- trials for groups
      with T+T-; T- and T0 alone trials). The results do not demonstrate an essential
      role for CS-alone trials in serial conditional discrimination procedures.
      Implications of the target 'ambiguity' and of the proportions of reinforced and
      nonreinforced trials for the nature of learning in conditional discrimination are
      discussed. 

PMID- 24897195
TI  - Previous- and following-component contrast effects using a three-component
      multiple schedule.
AB  - Behavioral contrast can be defined as an inverse relation between the rate of
      behavior in one component of a multiple schedule of reinforcement and the
      conditions of reinforcement in another component. In the present experiment, four
      pigeons pecked a key for mixed-grain reinforcers delivered by a three-component
      multiple schedule. During baseline conditions, the same variable-interval
      schedule was in effect during each component. In contrast conditions, the rate of
      reinforcement in the second component was increased or decreased. Behavioral
      contrast was usually observed in both the first and third components. Across
      component contrast effects were neither larger nor more reliable when the change
      in reinforcement occurred in the following component than when it occurred in the
      previous component. Furthermore, in both the first and third components, the size
      of contrast was almost always largest early in the component and decreased as the
      component progressed. Both across- and within-component data were analyzed using
      the model proposed by Williams and Wixted (1986). The results question the
      adequacy of the model. The results also pose difficulties for several existing
      theories of contrast. 

PMID- 24897193
TI  - Marking of nest entrance vicinity in the ant Pheidole pallidula (Formicidae,
      Myrmicinae).
AB  - The present work demonstrates the marking of the immediate vicinity of the nest
      entrances in the ant Pheidole pallidula. These areas attract and arrest nestmates
      but deter alien ants; they are the nearest approached by nestmates, which ants
      walk also the more in their midst. On such areas, nestmates are quieter when
      alone and more aggressive in the close presence of an intruder than on virgin
      areas, whereas alien ants are more excited and less inclined to attack. The
      vicinity of the nest entrances is thus perceived as being territorially marked,
      according to Holldobler and Wilson's definition (1990), and the different
      agonistic behaviour of intruder and resident workers on such a marked area
      reflects what is known as a Bourgeois strategy. The colony-specific marking of
      the nest entrance vicinity is established slowly and is rather long-lasting: it
      becomes obvious after 12 h and persists for nearly the same time. The marking is
      produced by non-recruited minor workers leaving their nest and walking around the
      entrance before going any further. It is not due to the deposit of faecal
      material, nor of secretions from the poison or the Dufour glands. The legs,
      fragments of legs, thorax, third segment of thorax and metapleural glands of
      minor workers all present an ethological activity identical to that of a
      territorially marked area. An acetone extract of minors' metapleural glands is
      active. Therefore, it appears that the minors mark the immediate vicinity of the
      nest entrances by depositing by their legs the metapleural gland contents. 

PMID- 24897196
TI  - Prevention of stereotypic wire-gnawing in laboratory mice: Effects on behaviour
      and implications for stereotypy as a coping response.
AB  - Three groups of six pairs of adult male laboratory mice of the ICR-strain kept in
      standard laboratory cages were selectively prevented from stereotypic wire
      gnawing for 1, 5 or 10 days, respectively. Behaviour was observed throughout the
      12 h dark period one day prior to prevention, on day 1, 4 or 9 (depending on the
      group) during the period of prevention and on post-inhibitory day 1 and 3. Prior
      to prevention wire-gnawing was positively correlated (P<0.05) with total activity
      and climbing. During prevention all three groups showed a significant reduction
      in total activity (non-stationary; P<0.05) and climbing (P<0.001) and
      significantly enhanced inactivity (lying motionless; P<0.05). However, the
      decrease in total activity was positively correlated with base levels of wire
      gnawing only on day 1 (P<0.01) but not at later stages of prevention. Similarly,
      climbing during prevention was positively correlated (P<0.05) with base levels of
      wire-gnawing on day 1 and 4 but not on day 9 of prevention. These results
      indicate that the mice only gradually adapted to the new situation. On post
      inhibitory day 1 all three groups resumed wire-gnawing at pre-treatment base
      levels with performance following the same time course throughout the dark period
      but with significantly reduced peak performance (P<0.05). In the light of
      motivational theory these results shed doubt on the general validity of the
      coping hypothesis. Two alternative explanations are discussed. 

PMID- 24897197
TI  - Some empirical data concerning time of day effects on conditioned freezing in an
      aversive context-conditioning procedure.
AB  - The primary purpose of this article is to present some empirical data concerning
      three different potential time of day effects on conditioned freezing in a
      commonly-used aversive context-conditioning procedure with an unsignalled
      electric footshock as the unconditioned stimulus. In Experiment 1, rats were
      repeatedly placed in a conditioning box in which they received a shock. For one
      group of rats, these sessions consistently occurred in the morning; for another
      group in the afternoon. In Experiments 2 and 3, rats received two training
      sessions per day. One group was consistently shocked in a training box on morning
      sessions but not on afternoon or evening sessions, whereas another group received
      the reverse treatment. The pattern of freezing observed during repeated non-shock
      morning and afternoon/evening test sessions reflected an effect of time of shock
      delivery on the acquisition of a context-shock association in Experiments 1 and
      2, and a time of testing, or non-specific performance, effect in Experiments 1
      and 3. In none of the experiments was there an effect that would reflect
      differential retrieval of a context-shock association by time cues. These results
      were discussed in the light of data from previous experiments. 

PMID- 24897198
TI  - [Nutritional status of beneficiaries of the Bolsa Familia Program in Brazil - a
      systematic review].
AB  - Various programs to combat malnutrition have been implemented over the years in
      Brazil. Since 2001, it has been the responsibility of the Bolsa Familia Program
      (BFP). Despite the expansion of BFP, to date there has been little coverage
      charting the advances and challenges to be faced as well as the impacts on health
      and nutrition of the population. Although the monitoring of nutritional status is
      one of the conditions for continuing to receive the benefit, when searching for
      this data, there is great difficulty in obtaining them. The scope of this
      systematic review is to obtain information on the nutritional status of the
      beneficiaries of the PBF, to grasp the national reality with regard to this
      situation, and assess whether the program had an impact on the nutritional status
      of the population served. A search was conducted online via Medline, Bireme,
      SciELO, Lilacs, University Libraries System (ULS) and Google. The search includes
      original articles and theses from March 2002 through May 2012 and
      approximately100 works were located. After excluding the title there were 23
      articles, and after reading the abstracts, 13 articles remained. The studies
      reviewed suggest that the Program is not modifying the nutritional status of the
      beneficiaries. 

PMID- 24897199
TI  - [Evaluation of public policies and initiatives in food and nutrition security:
      dilemmas and methodological perspectives].
AB  - The scope of this article is to analyze the main challenges and perspectives
      linked to the evaluation of public policies in food and nutrition security. The
      conclusion reached is that considering the complexity of actions in this area, it
      is important to discuss the limits of traditional evaluation strategies and move
      forward with the creation of new theoretical and methodological alternatives. 

PMID- 24897200
TI  - [Bolsa Familia: food and nutrition insecurity of children under five years of
      age].
AB  - This is a descriptive cross-sectional study of the population base conducted in
      the town of Colombo in the state of Parana. The objectives were to identify the
      prevalence of food insecurity in families that are beneficiaries of the Bolsa
      Familia Program and the factors related to this condition, and describe the
      nutritional status of children under five years of age. Analyses of association
      were performed using Fisher's exact test. The sample included 442 families, of
      which 168 have children under five years of age. The Brazilian Food Insecurity
      Scale was applied to evaluate food insecurity and the nutritional status of the
      199 children evaluated was determined by the height-for-age, weight-for-age and
      body mass-for-age indices in accordance with the WHO reference values for 2006.
      The prevalence of food insecurity was 81.6%. Overweight and stunting among
      children coexisted. Food insecurity was found to be associated with the height
      for-age index among children under two years of age. The per capita income and
      food deficits influenced the situation of food insecurity significantly. 

PMID- 24897201
TI  - [Comparative study of the nutritional evolution of patients/candidates for
      bariatric surgery attended by the Unified Health System and the Supplemental
      Health Network].
AB  - A cross-sectional comparative study was conducted on the nutritional evolution of
      severely obese patients who are candidates for bariatric surgery attended by the
      Unified Health System (SUS) and the Supplemental Health Network (RS). The average
      preoperative follow-up period was 14.3 +/- 7.7 months in the SUS and 2.4 +/- 1.7
      months in the RS. There was a predominance of females among patients attended by
      the SUS (80.6%) and by the RS (75.7%). A significant reduction in weight, BMI and
      waist circumference (WC) and total cholesterol values of patients of both health
      networks was observed. Patients attended by the SUS showed no significant
      decrease in LDL, Triglycerides and Fasting Glycemia, while patients assisted by
      the RS showed a significant reduction of these values. The greater weight loss
      among SUS patients is explained by the fact that they had been monitored for a
      longer period. The insignificant reduction of most biochemical indicators of SUS
      patients can be justified by the fact that they had a more advanced degree of
      obesity. 

PMID- 24897202
TI  - [Factors associated with being overweight among adults using low-budget
      restaurants in Belo Horizonte, Brazil].
AB  - The scope of this article is to assess the nutritional status of users of low
      budget restaurants and soup kitchens in Belo Horizonte and to identify factors
      associated with being overweight. It involved a cross-sectional analytical study
      conducted among adults of both sexes in low-budget restaurants and soup kitchens
      in Belo Horizonte. Being overweight was the dependent variable and was defined as
      body mass index (BMI) >= 25 kg/m2. This was correlated with socio-demographic
      variables and the level of physical activity. The data were obtained directly
      through weight and height measurement and a semi-structured questionnaire. The
      study involved 1334 individuals, the majority being male. The prevalence of being
      overweight was 42.9% among the men and 45.8% among the women. The following
      factors were positively associated with being overweight: being older for both
      sexes; having a partner for the women; taking less physical exercise and higher
      socioeconomic level for the men. Detection of factors associated with being
      overweight reveals that there is a need to implement an effective systematic
      program of dietary and nutritional education in order to prevent and remedy this
      condition, so that low-budget restaurants fulfill their objective.

PMID- 24897203
TI  - [Utilization and coverage of a Food and Nutritional Surveillance System in Rio
      Grande do Sul state, Brazil].
AB  - This article seeks to describe the utilization and coverage percentage of the
      Nutritional and Food Surveillance System (SISVAN-Web) in the Regional Health
      Offices of Rio Grande do Sul in 2010 and to assess its correlation with socio
      economic, demographic and health system organization variables at the time. It is
      an ecological study that used secondary data from the SISVAN-Web, the Department
      of Primary Health Care, the IT Department of the Unified Health System and the
      Brazilian Institute of Geography and Statistics. The evaluation of utilization
      and coverage data was restricted to nutritional status. The percentage of
      utilization of SISVAN-Web refers to the number of cities that fed the system.
      Total coverage was defined as the percentage of individuals in all stages of the
      life cycle monitored by SISVAN-Web. It was found that 324 cities fed the
      application, corresponding to a utilization percentage of 65.3%. Greater system
      coverage was observed in all Regional Health Coordination (RHC) Units for ages 0
      to 5 years and 5-10 years. There was a significant association between the
      percentage of utilization of SISVAN-Web and Family Health Strategy coverage in
      each RHC Unit. The results of this study indicated low percentages of utilization
      and coverage of SISVAN-Web in Rio Grande do Sul. 

PMID- 24897204
TI  - [Are there irrationalities in the consumption of anti-obesity drugs in Brazil? A
      pharmaco-econometric analysis of panel datasets].
AB  - The scope of this study is to analyze the determinants of the use of appetite
      suppressants (amfepramone, femproporex, mazindol and sibutramine) through the
      estimation of a dynamic panel dataset model for the Brazilian state capitals and
      the Federal District (DF) in the period from 2009 to 2011. The results show that
      consumption of appetite suppressants did not follow the geographic distribution
      of overweight and obese individuals across the capitals and DF. There is a
      recurrent consumption of appetite inhibitors, in which 79% of the current
      consumption of these drugs is explained by past consumption. Among the variables
      that explain the use of inhibitors, the percentage of obese adults, the
      percentage of adults who habitually consume fruit and vegetables, and the
      coverage rate of health plans stand out. The pharmaco-econometric analysis
      suggests that there are problems in the rational use of appetite suppressants in
      the Brazilian state capitals and the Federal District with respect to both the
      combined consumption of these drugs with other medicines - deemed illegal by the
      Federal Council of Medicine and ANVISA - and in the therapeutic prescription of
      these products. 

PMID- 24897205
TI  - [Gestational weight gain and birth weight of the newborn: a cross-sectional study
      in Jundiai, Sao Paulo, Brazil].
AB  - The aim of this study was to determine the prevalence of overweight, pre
      pregnancy and gestational obesity and verify the association with the birth
      weight of the newborn. A descriptive cross-sectional study was conducted with 712
      pregnant women admitted for delivery at the School of Medicine of Jundiai
      hospital. The variables studied were socio-demographics, pregnancy, pre-pregnancy
      weight, prenatal care, total gestational weight gain and birth weight of the
      newborn. The majority (99.7%) had a pre-natal and 84.6% > 6 visits. The
      prevalence of pre-pregnancy overweight was 34.7%, and excessive total weight gain
      was 36.9%. A significant association was observed between the pregnant women's
      BMI classification and the newborn's weight (NB) classification and between total
      weight gain classification of the mother and the newborn's weight classification.
      In pregnant women with excessive weight a higher prevalence of newborns with
      appropriate weight was observed. In contrast, women with insufficient weight gain
      had 2.15 times higher risk of underweight newborns and 2.85 times higher risk of
      low weight newborns. Although a significant percentage of overweight pregnant
      women was observed, this influenced the insufficient weight of the pregnant woman
      though not the birth weight of the newborns. 

PMID- 24897206
TI  - [Risk of chronic non-communicable diseases in the population attended in the
      nutritional education program in Goiania in the state of Goias, Brazil].
AB  - The scope of this work was to evaluate the risk factors for chronic non
      communicable diseases (CNCDs) in subjects treated in the Nutrition Education
      Program of the School of Physical Education of the Federal University of Goias.
      The number of individuals evaluated was 79, namely 65 adults and 14 adolescents.
      Socio-economic data, lifestyle and previous diseases were recorded by using
      anamnesis, the feeding habits (FH) were assessed by a food frequency
      questionnaire and the anthropometric indexes used were body mass index (BMI) and
      waist circumference (WC). The prevalence of overweight and obesity in the
      population was 42.9% (n = 27) and the average WC of adults was 82.67 +/- 12.49,
      and 45.1% had increased or very increased risk of cardiovascular diseases. About
      88.6% of the population reported the existence of CNCDs in the family. Most of
      the people (75%) exercised regularly. Those who smoked also drank alcohol
      frequently, and those that did not smoke were the ones that exercised more. The
      intake of fruit and vegetables is practiced by 36.7% and 63.3% of participants at
      least once a day, respectively. The conclusion reached is that the population
      studied had a high prevalence of exposure to at least one risk factor for CNCDs. 

PMID- 24897207
TI  - [The socio-cultural and eating aspects of women experiencing risk pregnancies].
AB  - To promote a healthy diet, the dietary guidance should consider socio-cultural
      factors as they influence both the food standards and preferences of each
      population. The aim of this study was to describe the socio-cultural contexts of
      pregnancy and feeding in the domestic arena, using a qualitative approach. In
      depth interviews were conducted using the data saturation technique with six
      women experiencing high-risk pregnancy. The interviews were transcribed and
      analyzed in accordance with the Bardin method and the IT Atlas program. The
      following aspects were identified: uncertainty due to unplanned pregnancy and
      limited partner support; a few dietary changes to improve health; perception of
      bad and good feeding habits, although it did not comply with the characteristics
      of a good diet; omission of fruit and vegetable group from dinner. The people in
      charge of preparing and serving food were not always the pregnant woman; food
      products perceived as being harmful were consumed and beneficial products were
      rarely consumed. This highlighted the need to train professionals to consider the
      socio-cultural context when providing dietary guidance. 

PMID- 24897208
TI  - [Evaluation of the inclusion of organic food from family-based agriculture in
      school food in municipalities of rural territories of the state of Rio Grande do
      Sul, Brazil].
AB  - Organic food enables the promotion of Food and Nutritional Safety (FNS) and
      sustainable regional development. In this context, the National School Food
      Program (NSFD) seeks to comply with the requirements of FNS. This study evaluated
      the inclusion of organic food in school food in the municipalities of rural
      territories of the state of Rio Grande do Sul by means of interviews with local
      managers. Eight territories were visited, albeit of its 153 municipalities only
      102 comprised the sample for this study. Of these, 20.58% said they buy organic
      produce from family farms. The Center South Territory revealed the highest
      percentage of purchase, in which 40% of the municipalities visited purchased
      organic produce, followed by the Center Mountain Territory with 33.3%, while the
      lowest percentage was 7.1% in the Countryside Territory. The study identified the
      need for intersectoral action to develop organic production, as well as stimulate
      the consumption of these foods in the school environment, in order to meet the
      requirements of FNS. 

PMID- 24897209
TI  - [Evaluation of the usability of a mobile Digital Food Guide based on user
      perception].
AB  - The use of digital technology in the form of health care apps has been on the
      increase. In the nutrition area, apps are now available with a view to lead to
      behavior change, helping individuals to reflect on their food choices and
      identify weak points in their dietary routine. The article seeks to evaluate user
      perception regarding the usability of the Digital Food Guide (DFG), which is a
      mobile smartphone app with guidelines on healthy eating. A cross-sectional study
      evaluated the user perception of the app using the Likert scale, built with 24
      assertions organized in three dimensions of analysis: the DFG as an intuitive and
      self-explanatory tool; the DFG as a promoter of healthy food choices; and the DFG
      as a promoter of the transition to the appropriate weight. The instrument was
      assessed regarding its reliability through the split-half and validity method in
      two stages. The 22 assertions were validated; the reliability was 0.93; the
      average of the assertions in each dimension was 3.10; of the 80 respondents,
      58.75% considered the implementation of the DFG to be positive. The application
      has good usability as perceived by users, considering analysis of the dimensions
      relating to its performance. 

PMID- 24897210
TI  - [Dietary risk patterns for non-communicable chronic diseases and their
      association with body fat - a systematic review].
AB  - The article seeks to review studies on unhealthy eating patterns for chronic non
      communicable diseases (NCD) and its association with body fat in adults,
      published between 2005 and 2012. The articles were systematically reviewed by two
      independent researchers in Medline, Lilacs, and Scielo using the following key
      words: food consumption, chronic diseases, anthropometry, body fat, and adults.
      Eight studies met the inclusion criteria, all conducted on the Brazilian
      population. The prevalence of overweight and abdominal fat ranged from 38.6% to
      51.3% and 23.4% to 43.1%, respectively. In the majority of studies, fruit and
      vegetable consumption was below the recommended level. A significant association
      between food patterns and anthropometric profile was found in five studies. The
      variations in the prevalence and in the results of the studies indicate the need
      for standardization of data collection instruments and methods used, as well as
      conducting studies with a more appropriate design. The high prevalence of
      overweight and low consumption of food meeting healthy eating standards indicates
      the need for intervention measures. 

PMID- 24897211
TI  - [Matrix of food and nutrition actions in primary health care: a benchmark for
      training of nutritionists in the context of education by skillsets].
AB  - This study had two objectives, namely to conduct a critical review of studies
      that underpin the training and practice of nutritionists in the context of
      Primary Health Care (PHC) in the Unified Health System (SUS), and evaluate the
      contribution of the matrix of food and nutrition actions in primary health care
      in this discussion. A protocol was developed to conduct the review in a
      systematic way. For the selection of studies, major databases were consulted,
      i.e. those used in health facilities, using intersections of the key search
      words: Nutritionist, National Policy on Food and Nutrition; National Curriculum
      Guidelines on health, Skill-based education; PHC. The array of actions can
      contribute to the training of nutritionists in the context of skill-based
      education to serve as a benchmark for actions, skills and abilities to train
      individuals, such that they are better able to cope with the needs of the
      population with emphasis on the SUS. Using it as a benchmark for training can
      contribute to the improvement of the latter and governmental actions based on the
      adoption of action on food and nutrition in PHC, in an effort complementing
      actions of all the other health programs, in particular the Family Health
      Strategy. 

PMID- 24897212
TI  - [Food insecurity and anthropometric, dietary and social indicators in Brazilian
      studies: a systematic review].
AB  - The scope of this systematic review was to relate food insecurity, detected using
      the Brazilian Food Insecurity Scale (EBIA), with anthropometric, dietary and
      social indicators. The search was conducted in electronic databases (ScieLO,
      LILACS, MEDLINE), with a selection of studies by titles and abstracts, and later
      full reading. Studies identified in bibliographic references were included. Of
      the 215 reviewed, 15 fulfilled inclusion criteria (association between insecurity
      and anthropometric, dietary or social indicators, detected by the EBIA), whereby
      three had more than one variable of interest. A relationship was observed between
      food insecurity and height/age and weight/age of child indices, as well as
      obesity in women. Lower consumption of regulating, tissue-building food products
      and iron, and higher carbohydrate intake are associated with food insecurity.
      There was a relationship between social indicators, such as lower income and
      education, lack of employment and basic sanitation. The EBIA was associated in
      some studies with nutritional and social indicators, but should be used in
      conjunction with other tools in order to cover the multiple dimensions of food
      and nutrition security. 

PMID- 24897213
TI  - [Street food in the national agenda of food and nutrition security: an essay for
      sanitary qualification in Brazil].
AB  - In 2014, the World Cup will be staged in Brazil. Is Brazil able to ensure safe
      street food is on offer? This paper seeks to elicit reflection on some problems
      relating to the sale of street food, thereby contributing to highlight this theme
      in the food security agenda in Brazil. The scope of this study is exclusively
      street food. Care is taken not to reduce the broader concepts of food security
      and the importance of sanitary and hygienic handling is stressed as one of the
      core components of food and nutrition security. In this context the following
      aspects are discussed: the credibility of the official data on insanitary
      outbreaks related to street food; street food security compared to that in other
      eating environments; and the training of people to modify inadequate food
      handling practices. Thus, in the discussion about problems in the street food
      market it is essential to improve the quantity and quality of the training of
      food handlers in order to implement food and nutrition security as promoting the
      human right to adequate food and ensure that the topic is urgently included on
      the national calendar of public health debates. 

PMID- 24897214
TI  - [Risk factors of stunting in preschool children: a case-control study].
AB  - This article seeks to establish risk factors for mild and moderate stunting among
      preschool children attending public daycare centers. It involves a case-control
      study with 67 pairs of children. Cases defined as children with height/age
      between -1 and -2 Z-scores were paired with controls between -1 Z-score and the
      median, while cases with height/age < -2 Z-scores were paired with controls with
      height/age > median to +1 Z-score. The sex and age of the child was used for
      pairing purposes. The final model of hierarchical multivariate analysis indicated
      a greater chance of stunting in the following groups of preschoolers: family
      income < 1/2 Minimum Wage, squatted/courtesy house, number of individuals in the
      household >= 6, maternal age at child's birth < 20 years, low maternal stature,
      incomplete immunization program, low birth weight. Stunting is determined by
      adverse socioeconomic conditions and the characteristics of children reflecting
      health care (maternal height and child variables).

PMID- 24897215
TI  - [Factors associated with the addition of salt to prepared food].
AB  - The scope of this research was to investigate the potential differences between
      men and women in the addition of salt to prepared food. The study included 47,557
      individuals aged 18 to 64 participating in the Risk and Protection Factors for
      Chronic Disease Surveillance System by Telephone Interview carried out in 26
      Brazilian state capitals and the Federal District in 2006. Differences between
      men and women were tested by the chi-square test and the association magnitudes
      between the dependent and independent variables were estimated by the Odds Ratio
      obtained by Multiple Logistic Regression analysis. The prevalence of the addition
      of salt to prepared food was 8.3%, being higher among men (9,8% vs 6,9%, p <
      0.01). After adjustment, the addition of salt to prepared food was higher in
      individuals with self-rated fair to poor health, reporting cardiovascular disease
      and living in the North of Brazil. Hypertensive individuals reported addition of
      less salt to prepared food. Educational level was not associated with salt usage.
      Men add more salt than women. Public health policies aimed at reducing salt
      intake by the population should take into account the gender differences in salt
      intake and the factors that contribute to such differences. 

PMID- 24897216
TI  - [Factors associated with the consumption of high-fat foods among adults in a
      Southern Brazilian city].
AB  - The scope of this study was to describe the frequency of consumption of high-fat
      foods among adults aged 20 to 69 years and to identify associated factors. A
      population-based cross-sectional study was conducted with 972 adults in Pelotas,
      Southern Brazil. The consumption of high-fat foods in the previous twelve months
      was evaluated using the Block questionnaire comprising fifteen food items scored
      according to the frequency of consumption of high-fat foods. Approximately one in
      every three adults (32.7%) reported the regular consumption of high-fat diets.
      Among individuals of both sexes, the regular consumption of fat was associated
      with younger ages and the regular intake of non-diet soft drinks, and only for
      men, to the A/B economic levels. The conclusion reached is that the consumption
      of high-fat food among adults is above current Ministry of Health
      recommendations. Interventions aimed at stimulating healthy diets are urgently
      needed. 

PMID- 24897217
TI  - [The risks and the promotion of self-control on nutritional health: morality,
      biopolitics and parrhesiastic critique].
AB  - This paper deals with proposals for self-care by means of self-control in the
      promotion of nutritional health, especially in the quest to avoid weight gain and
      the consumption of food that does not meet 'healthy food' guidelines. These
      initiatives present themselves as self-care strategies that are legitimated and
      enshrined in the context of nutritional heath, linked with moralistic modes on
      the current ways of leading our lives. The study's critical standpoint adopts a
      biopolitical approach and 'cynical parrhesia' as an argumentative line of
      reasoning, which is in line with Cynicism as a philosophical doctrine,
      subsequently developed by Michel Foucault in his studies on care of the self. 

PMID- 24897218
TI  - [Prevalence and factors associated with food and nutrition insecurity in families
      in municipalities of the north of the State of Alagoas, Brazil, 2010].
AB  - The scope of this study was to identify the prevalence and factors associated
      with food insecurity (INSEC) in families of northern Alagoas. A cross-sectional
      study was conducted with a random sample of 1444 households classified in
      accordance with the Brazilian INSEC scale into the following categories: mild,
      moderate or severe. The prevalence ratio calculated by Poisson regression was
      used to investigate the association of moderate + severe INSEC with the
      independent variables in both crude and adjusted analysis. The variables that in
      the crude analysis reached p < 0.2 were included. INSEC was detected in 919
      families, of which, 23.3% and 14.2% were in the moderate or severe form,
      respectively. There was a higher proportion of food insecurity in the families
      with subjects < 18 years. The variables that remained independently associated to
      moderate + severe food insecurity were: rooms in the household <= 4, schooling of
      the household head <= 4 years, drinking water other than mineral, beneficiary of
      the Bolsa Familia Program, number of residents in the household > 4, head of
      household is female and schooling of the housewife <= 4 years. The conclusion was
      that the families studied showed a high prevalence of INSEC, especially those
      with individuals < 18 years.

PMID- 24897219
TI  - [Population coverage of the food and nutrition surveillance system in the state
      of Sao Paulo, Brazil].
AB  - This article sets out to estimate the population coverage of the Food and
      Nutrition Surveillance System (SISVAN) at different phases of life and to
      evaluate its operation in the state of Sao Paulo. The study included 65 cities
      divided in 14 state regions. The coverage of SISVAN was estimated using data from
      nutritional status monitoring available in public reports and on government
      websites, as well as the number of users attended by the public health services.
      Total users of public health services were obtained by the difference between the
      total number of inhabitants of 65 cities and the number of beneficiaries of
      private health plans. Most regions presented reduced population coverage (< 10%).
      Approximately 57% revealed population coverage of between 5 and 10%. There was a
      preponderance of records of the nutritional status of children for all regions of
      the state. A startling statistic was the low coverage for the elderly population,
      which was zero or near zero in most regions. Despite the efforts by the
      government to expand and enhance SISVAN, nutritional monitoring in Sao Paulo is
      still insufficient. This condition hinders the use of SISVAN to produce effective
      changes in food and nutrition policies. 

PMID- 24897220
TI  - [Profile of food handlers in the home].
AB  - This article seeks to diagnose the profile of food handlers in the households of
      the city of Santa Maria in the state of Rio Grande do Sul. By geographical
      division of the city, a sample of 15 households per neighborhood was chosen,
      totaling 615 households. For the diagnosis of the profile of handlers in the
      households, a questionnaire was prepared, containing 6 open questions and 13
      closed questions related to personal data including gender, marital status,
      education, occupation and monthly income. Issues such as the frequency with which
      people prepare meals in the households and satisfaction in preparing them, as
      well as participation in courses and the perception of food safety, were also
      addressed. It was found that 92.5% of the food handlers were female, 52.2% had
      complete or incomplete primary school and 35.4% had a monthly income of between 3
      and 9 minimum wages. Among those interviewed, 82.6% reported that they prepare
      meals every day of the week and 77.9% reported that they never had problems
      caused by the food produced at home. It is important to evaluate the profile of
      food handlers in the households, as this makes it possible to develop strategies
      to prevent or diminish foodborne diseases. 

PMID- 24897221
TI  - [Training for female shellfish gatherers on food safety and worker's health: an
      experience in the community of Ilha do Paty, Brazil].
AB  - This study describes an experience in the training of female shellfish gatherers
      in the fishing community in Ilha do Paty, Sao Francisco do Conde, within the
      context of actions to promote health and food safety. This is an intervention
      study with planning of activities by a multidisciplinary team. The activities
      were developed in five stages: survey of topics of interest; awareness; female
      shellfish gatherers' work routine; teaching of best practices in the processing
      of shellfish; and group conversation. The methodologies included exposure through
      dialogue, group dynamics, workshops, theater, work with images, directed
      activities and the distribution of educational materials. At the end, an
      evaluation by the participants regarding the different aspects was conducted.
      Overall there was satisfaction among the audience for most indicators, which may
      relate to both the use of audiovisual resources and strategies that permitted the
      exchange of experiences regarding the recognition of the importance of training
      by the target audience. The experiment demonstrates the potential of developing
      educational activities with the fishing communities, with results that contribute
      to the bolstering of the local supply chain, with the promotion of food safety
      and occupational health. 

PMID- 24897222
TI  - [Nutritional status of patients with breast cancer attended in the Mastology
      Service of Belo Horizonte's Hospital das Clinicas in the state of Minas Gerais,
      Brazil].
AB  - The scope of this article is to evaluate the nutritional status, body composition
      and tumor characteristics of 31 patients with breast cancer attended at the
      Mastology Service of Hospital das Clinicas of the Federal University of Minas
      Gerais. Dietary data were obtained from the 24-hour dietary recall in the pre
      operative state and analyzed by the DietWin Professional 2008 Nutrition Software.
      Body composition was assessed by bioelectrical impedance analysis. The tumor
      characterization data were collected from medical records. The mean age of
      patients was 50.75 +/- 14.34 years. Excess body weight was found in 58% and waist
      circumference greater than 80 cm in 64.5% of patients Excessive consumption of
      oils and sugars was observed in 90.3% and 83.8%, respectively. Most had low
      intakes of calcium and vitamins B6, B12 and A. The predominant diagnosis was type
      II histological grade invasive ductal carcinoma in stage II or III. The
      prevalence of overweight and inadequate dietary intake demonstrate the need for
      individualized nutritional guidance and monitoring to improve the prognosis and
      quality of the life of patients. 

PMID- 24897223
TI  - [Nutritional deficit in children in a major city of the interior of the state of
      Bahia, Brazil].
AB  - The study sought to analyze the nutritional deficit of children and associated
      environmental factors and maternal and infant characteristics in a major city in
      the interior of the state of Bahia. Information from mother/child-under-four duos
      of a birth cohort was assessed. Malnutrition was defined by the height-for-age
      (H/A) anthropometric index, at a cutoff of -1 z-score relative to the benchmark
      of the 2006 Multicentre Growth Reference Study. The variables studied were: the
      characteristics of children (birth weight and multiple births) and mothers (age
      at the time of birth, education level, parity and performing prenatal exams) and
      environmental factors (floor and roof material of residence, source of water
      consumed, indoor plumbing, water used for consumption and ownership of a
      refrigerator). Logistic regression was used to identify factors associated with
      nutritional deficit. Nutritional deficit occurred in 24.6% of children.
      Underweight at birth, inadequate prenatal care, precarious nature of the floor of
      the home and no indoor plumbing were predictors of malnutrition among children in
      the study. Factors associated with malnutrition confirm the contribution of
      social issues in the genesis of malnutrition. 

PMID- 24897224
TI  - [Frequency of adherence to the "10 Steps to Healthy Eating" among school-aged
      adolescents].
AB  - The scope of this study was to evaluate the frequency of adherence to "10 Steps
      to Healthy Eating" of the Ministry of Health in adolescents from high schools in
      Pelotas in the state of Rio Grande do Sul, Brazil. A school-based cross-sectional
      study was conducted, including 1233 adolescents (13-19 years of age). The
      frequency of each step was evaluated through a questionnaire on food frequency
      and other issues included in the "10 Steps." The average number of steps achieved
      was 1.8. It is noteworthy that none of the subjects achieved entirely all the
      recommended steps. The highest frequency of compliance was found in step 4,
      referring to the consumption of the rice and beans. Lower frequencies of
      adherence were found for step 7, related to consumption of soft drinks, processed
      juices, sweets and snacks, and also step 3 on the consumption of
      fruit/vegetables/greens. Adherence to the "10 steps to Healthy Eating" by
      adolescents was very low. Considering the importance of healthy eating in
      adolescence, greater investment in public policies in the area of food and
      nutrition is strongly recommended. 

PMID- 24897225
TI  - [Determinants of food and nutrition insecurity: a study conducted in Low-budget
      Restaurants in Belo Horizonte in the state of Minas Gerais, Brazil].
AB  - The scope of this study is to evaluate the condition of household food and
      nutrition (in)security (IAN) of the users of low-budget restaurants in Belo
      Horizonte (BH). This is an analytical cross-sectional study carried out on all
      low-budget restaurants and cafeteria in BH with a sample of 1613 users. The IAN
      was assessed using the Brazilian Food Insecurity Scale and cross-checked with the
      socioeconomic profile of the users. The Chisquare and Mann-Whitney tests were
      applied. All p-value < 0.25 variables were included in the multivariate analysis.
      The groups most exposed to IAN among users of low-budget restaurants are those
      with a lower socioeconomic level and per capita income class and those with a
      large number of residents in the household. Also affected are those who admit to
      having different kinds of wants and needs, and those for whom price and living
      alone are the main reasons for frequenting low-budget restaurants. The factors
      affecting the IAN are varied and multifactorial, thus representing a major
      challenge for public policy makers and for those who live directly with these
      dietary restrictions. The low-budget restaurants serve as a strategy for
      promoting healthy eating habits. 

PMID- 24897226
TI  - [Risk and protection food consumption factors for chronic non-communicable
      diseases and their association with body fat: a study of employees in the health
      area of a public university in Recife in the state of Pernambuco, Brazil].
AB  - This article seeks to assess the consumption of risk and protection foods for
      chronic non-communicable diseases and its association with body fat by health
      area workers in a public university in Recife in the state of Pernambuco. This
      cross-sectional study involved 267 adults. Two food groups were considered: risk
      and protection foods. Food consumption was assessed by a food frequency
      questionnaire with measurements converted to scores. The conceptual model
      considered socio-demographic, behavioral, and anthropometric variables. A high
      prevalence of overweight and low consumption of protection foods was detected.
      The average scores of risk and protection food consumption were similar in all
      variables analyzed, except for a higher consumption of protection foods observed
      in obese individuals (p = 0.000). The study highlights the complexity involved in
      the relation between food consumption, body fat, and chronic non-communicable
      diseases, indicating the need of future studies with more appropriate designs to
      provide input for future interventions in this population. 

PMID- 24897227
TI  - [Analysis of the nutritional composition of the Brazilian Staple Foods Basket].
AB  - This study sought to assess the nutritional status (energy, carbohydrates,
      proteins, lipids, calcium, iron, zinc, phosphorus, vitamin A and vitamin C) of
      the 13 items in the Brazilian staple foods basket and to verify whether they are
      suitable for the monthly subsistence of an adult. The values established by the
      Estimated Average Requirement were compared to those found in the study. It is a
      descriptive study that used information from a food composition table in order to
      analyze data regarding the Brazilian staple foods basket from the Inter-Union
      Department of Statistics and Socio-Economic Studies. Appropriate values were
      found for carbohydrates, proteins, iron, zinc, phosphorus. Total energy and
      lipids were above the recommended values, while calcium and vitamin A were below.
      Vitamin C had adequate values only for females. The Brazilian staple foods basket
      largely reflects the individual food intake. However, given the prevalence of
      obesity in the Brazilian population, some adjustments in this nutritional basis
      are required, so that it is rendered adequate in terms of macronutrient and
      micronutrient values. 

PMID- 24897229
TI  - Opioid modulation of socially transmitted and spontaneous food preferences in
      female mice.
AB  - The present experiments were conducted to investigate the possible role of
      endogenous opioid peptides in the social transmission of food preferences in
      female mice. In the first experiment, observer animals were injected with 0.5 mg
      kg(-1) naltrexone, a long-lasting opioid receptor antagonist, 30 min prior to a
      15-min period of social interaction with a familiar conspecific (demonstrator)
      fed either with a cocoa-flavoured or a plain diet. Afterwards, observers
      underwent a 30-min two-choice test between the cocoa and a more palatable,
      unfamiliar cinnamon diet. The results showed that opioid receptor blockade
      decreased the amount of cocoa diet consumed by the animals whose demonstrators
      ate cocoa diet. Experiment 2 showed that naltrexone, administered after the
      social interaction, strongly attenuated the expression of both a socially
      acquired preference for the cocoa diet and the spontaneous preference for the
      cinnamon diet. A third experiment was then conducted using the shorter-lasting
      opioid antagonist naloxone. Naloxone (0.5 mg kg(-1)) administered prior to the
      social interaction did not impair the acquisition of the food preference. Hence,
      results indicate that a blockade of opioid activity is sufficient to impair the
      expression of a socially acquired food preference but not its acquisition. 

PMID- 24897231
TI  - Luminance and chromatic discrimination in the horse (Equus caballus).
AB  - Equine colour vision was measured under conditions that minimised the possibility
      of animals using brightness cues to make chromatic discriminations. In a two
      stage study, we first obtained luminance discrimination functions for achromatic
      targets then tested for chromatic discrimination over a range of target
      luminances. Horses were trained on a two-choice discrimination task. The positive
      stimulus was varied in luminance and/or colour using neutral density and broad
      band colour filters. The negative stimulus appeared as a uniform grey. In the
      brightness discrimination task, the horses performed well at large luminance
      differences but their percentage of correct responses declined to near chance
      levels at differences of less than 0.2 log units. In addition, a decrement in
      performance was noted at luminance differences of less than 0.2 log units for
      green and yellow chromatic discrimination functions, suggesting that horses
      cannot easily discriminate yellow and green from grey. However, the chromatic
      discrimination functions for red and blue showed that animals performed very well
      across the full range of target luminances. These results suggest that horses are
      at least dichromats. 

PMID- 24897230
TI  - Rats are reluctant to use circadian timing in a daily time-place task.
AB  - On daily time-place learning tasks animals can work for food at different spatial
      locations during sessions at different times of the day. In previous experiments
      rats tracked this pattern of food availability with ordinal timing-they learned
      to respond at the locations in the correct order each day. In contrast, pigeons
      used circadian timing. In this experiment rats received a mixture of morning
      session only days, afternoon session only days, and morning and afternoon session
      days. Under these conditions ordinal timing had low predictive ability, but
      circadian timing was potentially perfectly predictive of the location of food
      availability. We thought this procedural change might encourage rats to use
      circadian timing. However, we found little evidence that rats can use time of day
      information to track this daily spatiotemporal pattern of food availability.
      These results are suggestive of differences in the use of circadian clock
      consultation by rats and pigeons. 

PMID- 24897232
TI  - Spatial generalization in honeybees confirms Shepard's law.
AB  - In stimulus generalization, a subject that has learned to respond to one target
      stimulus also responds to other similar stimuli. Shepard's law of generalization
      states that probability of responding decreases exponentially with psychological
      distance between test and target stimuli (Shepard, R.N., 1987. Toward a universal
      law of generalization for psychological science. Science 237, 1317-1323). In
      experiments on spatial generalization, honeybees were trained to find a target at
      a location near one principal landmark, and then tested with the target at
      different locations. A theoretical scale of positional mismatch between test and
      target locations was computed by a weighted sum of discrepancies between test and
      target locations in the compass direction (0.25 weight) and size (angle) of
      projected retinal height (0.375 weight) and width (0.375 weight) of the landmark,
      derived from the model of Cartwright and Collett (Cartwright, B.A., Collett,
      T.S., 1982. How honeybees use landmarks to guide their return to a food source.
      Nature 295, 560-564; Cartwright, B.A., Collett, T.S., 1983. Landmark learning in
      bees. J. Comp. Physiol. A 151, 521-543) of landmark use in honeybees. Based on
      the theoretical scale, but not on physical distance, Shepard's law fit data from
      four experiments, the first time it has been confirmed in an invertebrate. 

PMID- 24897233
TI  - Evidence for within-compound learning in an instrumental conditioning with rats.
AB  - Two groups of rats were trained with a multiple schedule of avoidance and
      punishment in a running wheel. During the punishment component, each of the
      subjects' running responses were punished. In contrast, they had to run during
      the avoidance component of Sidman avoidance schedule, in which the response-shock
      interval was 20 s and the shock-shock interval was 5 s. There was no nominal
      discriminative stimulus in the punishment component, whereas the avoidance
      component was signalled by a compound stimulus of tone and light (AX) in Stage 1
      for 6 days, by one of the element stimulus (A) of the previous compounds in Stage
      2 for 6 days and by another element stimulus (X) in Stage 3 for 2 days. The only
      difference between the two groups was that Group E experienced all three stages,
      while the subjects of Group C remained in their home cages during Stage 2. The
      avoidance performance were evaluated in Stage 3. Only Group E showed robust
      respondings to the stimulus (X) which was not reinforced by itself. These results
      were accounted by a within-compound association view. 

PMID- 24897234
TI  - Non-effects of mammillary body lesions on spontaneous alternation: pre and
      postoperative study.
AB  - This study was designed to investigate the potential effects of medial mammillary
      nucleus (MMn) lesions on spontaneous alternation behavior in rats. Behavioral
      measurements were made in a water T maze in which the side arms were not
      differentially reinforced. Spontaneous alternation was tested before and after
      surgery alone. In both experiments, volumetric estimates of the MMn lesion were
      made by stereologic calculations. The results obtained do not support the direct
      participation of the MMn in retrograde or anterograde memory processes related to
      spontaneous spatial alternation. 

PMID- 24897235
TI  - Pigeon homing: site simulation experiments with bird-borne direction recorders.
AB  - Previous experiments showed that pigeons allowed to smell olfactory cues at a
      'false' release site, and subsequently transported to and released from another
      unfamiliar locality, oriented according to the home direction at the false site
      but eventually homed despite their wrong initial orientation. In the above 'site
      simulation' experiments, data collection was restricted to the initial bearings
      and homing performance, and no information was obtained on the actual route flown
      by pigeons. Route correction in site simulation tests is now investigated by
      releasing pigeons equipped with bird-borne direction recorders to track their
      route. Our results show that the experimental birds can actually fly for a long
      time in wrong directions, related to the home direction at the false release
      site, before correcting their path to the true homeward direction. This
      correction occurs 2 h or more after release, when the birds are supposed to have
      recovered from the anaesthesia of their olfactory membranes which they had been
      subjected to just prior to release. This result confirms the basic role of the
      olfactory information, collected during the outward journey, in the pigeon's
      homing process. 

PMID- 24897236
TI  - The role of prior agonistic experience in dominance relationships in male
      crickets Gryllus bimaculatus (Orthoptera: Gryllidae).
AB  - Experiments were carried out to study the effect of social conditioning (prior
      experience of dominance and submission) in dominance relationships between adult
      male Gryllus bimaculatus. The dominance status of a male cricket appears to be
      directly linked to its immediate prior agonistic experience. An experience of
      dominance increases the probability of victory and one of submission decreases
      it. The effect is maximum when one opponent has experienced dominance and one
      subordination. The aggressive behavior of males is significantly influenced by
      prior agonistic experience for 6 h and the effect disappears entirely after 24 h.
      The cost and benefit of a conflict appears to be dependent on the motivational
      state of each opponent, in turn modulated by the outcome of prior agonistic
      interactions. 

PMID- 24897237
TI  - Interleukin-18 gene promoter--607 A/C polymorphism and the risk of immune
      thrombocytopenia.
AB  - Interleukin-18 (IL-18) is a T helper 1 cytokine, which is postulated to play a
      role in immune thrombocytopenia (ITP). The aim of this study was to determine
      whether IL-18 promoter gene -607 A/C polymorphism was associated with ITP. Three
      hundred and fifty-four Chinese ITP patients and 300 Chinese healthy individuals
      were enrolled. Genomic DNA was extracted from the peripheral blood. Polymerase
      chain reaction-restriction fragment length polymorphism (RFLP) was used to
      genotype the DNA samples for single nucleotide polymorphism (SNP)-607. Allelic
      and genotypic frequencies were compared between the case-control groups by the
      chi-square test. The results showed that the frequencies of the CC, CA and AA
      genotypes and C and A allele were 32.4, 47.8, 19.8, 56.4 and 43.6% in ITP
      patients and 32.3, 50.4, 17.3, 57.5 and 42.5% in the controls, respectively.
      There was no significant difference in either genotypes or allelic distribution
      between ITP patients and the controls. Furthermore, stratified analysis by the
      platelet count, age and disease course including ITP with severe thrombocytopenia
      (sITP), non-sITP, acute adult, chronic adult, acute childhood and chronic
      childhood revealed no significant difference in genotype and alleles
      distribution. In conclusion, this polymorphism was almost equally distributed
      between ITP patients and the controls. These data showed that this SNP may not be
      used as a stratification marker to predict the susceptibility to Chinese ITP.

PMID- 24897238
TI  - Intersubunit salt bridges with a sulfate anion control subunit dissociation and
      thermal stabilization of Bacillus sp. TB-90 urate oxidase.
AB  - The optimal activity of Bacillus sp. TB-90 urate oxidase (BTUO) is 45  degrees C,
      but this enzyme is one of the most thermostable urate oxidases. A marked increase
      (>10  degrees C) in its thermal stability is induced by high concentrations (0.8
      1.2 M) of sodium sulfate. Calorimetric measurements and size exclusion
      chromatographic analyses suggested that sulfate-induced thermal stabilization is
      related to the binding of a sulfate anion that repressed the dissociation of BTUO
      tetramers into dimers. To determine the sulfate binding site, the crystal
      structure was determined at 1.75 A resolution. The bound sulfate anion was found
      at the subunit interface of the symmetrical related subunits and formed a salt
      bridge with two Arg298 residues in the flexible loop that is involved in subunit
      assembly. Site-directed mutagenesis of Arg298 to Glu was used to extensively
      characterize the sulfate binding site at the subunit interface. The network of
      charged hydrogen bonds via the bound sulfate is suggested to contribute
      significantly to the thermal stabilization of both subunit dimers and the
      tetrameric assembly of BTUO. Knowledge of the mechanism of salt-induced
      stabilization will help to develop new strategies for enhancing protein thermal
      stabilization.

PMID- 24897239
TI  - Association of neuropeptide Y gene rs16147 polymorphism with metabolic syndrome
      in patients with documented coronary artery disease.
AB  - BACKGROUND AND AIMS: There have been few epidemiological studies that have
      investigated genetic susceptibility to cardiovascular risk associated with the
      prevalence of metabolic syndrome (MetS). Neuropeptide Y (NPY) is a strong
      candidate gene for coronary artery disease (CAD). Therefore, the aim of this
      study was to investigate the association between the NPY gene rs16147
      polymorphism and the presence of MetS in a well defined group of Iranian subjects
      with angiographically-defined CAD. METHODS: A cross-sectional study design was
      used in which a total of 364 patients were recruited; 143 patients with MetS and
      221 without MetS were genotyped using the ARMS-PCR technique. Logistic regression
      analyses were performed to determine the odds ratios (ORs) for the association of
      specific genotypes with the presence of MetS and related phenotypes. RESULTS: The
      frequency of the variant G allele of the NPY gene was significantly higher in CAD
      patients without MetS (p = 0.032). Compared to the AA genotype of the NPY gene,
      individuals carrying the GG genotype had a reduced risk of MetS (OR = 0.51, 95%
      CI = 0.27-0.95, p = 0.034). CONCLUSION: The rs16147 polymorphism may be
      associated with presence of MetS among subjects with documented CAD. Carriage of
      NPY A allele in patients with CAD is associated with a higher prevalence of MetS.

PMID- 24897242
TI  - Bayesian bivariate linear mixed-effects models with skew-normal/independent
      distributions, with application to AIDS clinical studies.
AB  - Bivariate correlated (clustered) data often encountered in epidemiological and
      clinical research are routinely analyzed under a linear mixed-effected (LME)
      model with normality assumptions for the random-effects and within-subject
      errors. However, those analyses might not provide robust inference when the
      normality assumptions are questionable if the data set particularly exhibits
      skewness and heavy tails. In this article, we develop a Bayesian approach to
      bivariate linear mixed-effects (BLME) models replacing the Gaussian assumptions
      for the random terms with skew-normal/independent (SNI) distributions. The SNI
      distribution is an attractive class of asymmetric heavy-tailed parametric
      structure which includes the skew-normal, skew-t, skew-slash, and skew
      contaminated normal distributions as special cases. We assume that the random
      effects and the within-subject (random) errors, respectively, follow multivariate
      SNI and normal/independent (NI) distributions, which provide an appealing robust
      alternative to the symmetric normal distribution in a BLME model framework. The
      method is exemplified through an application to an AIDS clinical data set to
      compare potential models with different distribution specifications, and
      clinically important findings are reported. 

PMID- 24897243
TI  - MALONEWS-gnawing at the roots of academic psychology.

PMID- 24897244
TI  - Female tamarins (Saguinus - Callitrichidae) feed more successfully than males in
      unfamiliar foraging tasks.
AB  - Fourteen adult male/female pairs of tamarins, 5 red-chested (Saguinus labiatus) 5
      saddle-back (S. fuscicollis) and 4 cotton-top (S. oedipus) were each given a
      series of foraging tasks in which the monkeys reached in to unfamiliar boxes to
      take food. Behaviour was recorded that related directly to the tasks. In
      addition, observations were made before each task presentation and compared with
      equivalent behaviour during the tasks. S. fuscicollis differed significantly from
      the other species in the baseline conditions and in the presence of the tasks,
      which they approached less frequently and for less time. Further, males and
      females across all species differed significantly in that females attempted the
      tasks more frequently, they spent longer periods attempting to solve them, and
      they removed food more often. These results were considered as evidence for male
      'deference' to a potentially reproductive female. 

PMID- 24897240
TI  - Allopurinol therapy in gout patients does not associate with beneficial
      cardiovascular outcomes: a population-based matched-cohort study.
AB  - INTRODUCTION: Previous studies have shown an association between gout and/or
      hyperuricemia and a subsequent increase in cardiovascular disease (CVD) outcomes.
      Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state,
      improves endothelial function, and prevents atherosclerosis progression.
      Accordingly, we tested the hypothesis that a positive association between
      allopurinol therapy in gout patients and future cardiovascular outcomes is
      present using a population-based matched-cohort study design. METHODS: Patients
      aged >=40 years with newly diagnosed gout having no pre-existing severe form of
      CVD were separated into allopurinol (n = 2483) and non-allopurinol (n = 2483)
      groups after matching for age, gender, index date, diabetes mellitus,
      hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also
      balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis,
      and Charlson comorbidity index. RESULTS: With a median follow-up time of 5.25
      years, the allopurinol group had a modest increase in cardiovascular risk
      [relative risk, 1.20; 95% confidence interval (CI), 1.08-1.34]. A Cox
      proportional hazard model adjusted for chronic kidney disease, uremia, and
      gastric ulcer gave a hazard ratio (HR) for cardiovascular outcomes of 1.25 (95%
      CI, 1.10-1.41) in gout patients receiving allopurinol compared with the non
      allopurinol group. In further analysis of patients receiving urate-lowering
      therapy, the uricosuric agent group (n = 1713) had an adjusted HR of 0.83 (0.73
      0.95) for cardiovascular events compared with the allopurinol group. CONCLUSIONS:
      The current population-based matched-cohort study did not support the association
      between allopurinol therapy in gout patients with normal risk for cardiovascular
      sequels and beneficial future cardiovascular outcomes. Several important risk
      factors for cardiovascular disease, such as smoking, alcohol consumption, body
      mass index, blood pressure were not obtainable in the current retrospective
      cohort study, thus could potentially bias the effect estimate.

PMID- 24897245
TI  - Species specificity of social reinstatement in Japanese quail Coturnix japonica
      genetically selected for high or low levels of social reinstatement behaviour.
AB  - Divergent lines of Japanese quail Coturnix japonica showing high (HSR) or low
      (LSR) levels of social reinstatement (SR) behaviour (as measured in a treadmill
      apparatus) have been developed. However, it was not known if selection had
      influenced social reinstatement tendencies in a general or a species-specific
      fashion. Therefore, the present study compared the SR behaviour of quail chicks
      of the HSR and LSR lines and of a Control line when the goal box of the treadmill
      was empty or when it contained small, same-species groups of either Japanese
      quail, domestic fowl or Guinea fowl chicks. The results clearly demonstrated that
      the SR behaviour of Japanese quail chicks is species-specific and that this
      specificity has not been influenced during genetic selection, over sixteen
      generations, of the HSR and LSR lines. The HSR chicks showed more locomotor
      activity in the treadmill than did those of the other lines regardless of the
      nature of the goal-box stimulus. The results are discussed in terms of general
      activity, underlying fearfulness and social motivation. 

PMID- 24897241
TI  - Phenotype standardization for statin-induced myotoxicity.
AB  - Statins are widely used lipid-lowering drugs that are effective in reducing
      cardiovascular disease risk. Although they are generally well tolerated, they can
      cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this
      area has been hampered to some extent by the lack of standardized nomenclature
      and phenotypic definitions. We have used numerical and descriptive
      classifications and developed an algorithm to define statin-related myotoxicity
      phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing
      autoimmune myopathy. 

PMID- 24897246
TI  - Experiential and genetic influences on learnt food aversions in Japanese quail
      selected for high or low levels of fearfulness.
AB  - Interactions between underlying fearfulness and social factors during the
      development of learnt food aversions was studied in two lines of Japanese quail
      selected for a long (LTI) or short (STI) duration of the tonic immobility
      response. Chicks of the LTI line have high inherent levels of fearfulness and
      chicks of the STI line have low levels of inherent fearfulness. Food aversions
      were conditioned by pairing blue coloration with the presence of Jackbean (which
      has mild post-ingestional toxic effects) in the animals feed. In each of 3
      training trials, chicks were exposed, either individually or in same line groups
      of four, to coloured or uncoloured diets containing toxic Jackbean or non-toxic
      Fieldbean. After training the preferences of chicks for coloured or uncoloured
      non-toxic diets were assessed in a choice test. Analysis of time spent feeding
      and amount of feed consumed in the choice tests suggested three levels of
      interaction between the fear state of the chicks and their reactions to
      unfamiliar and/or toxic feed. First, when fear levels are high (individually
      tested LTI line chicks), food which resembles a previously experienced toxic diet
      is rejected. Second, when fear levels are intermediate (individually tested STI
      line chicks), animals prefer food which resembles a previously experienced non
      toxic diet but do not totally reject food which resembles a previously
      experienced toxic diet. Third, when fear levels are low (group testing),
      previously experience of toxic or non-toxic diets has limited effects on food
      choice. Animals show a preference for diets with a form similar to that which
      they were fed during early life but this preference is to some degree modulated
      by more recent feeding experiences. 

PMID- 24897247
TI  - The opening of milk bottles by birds: Evidence for accelerating learning rates,
      but against the wave-of-advance model of cultural transmission.
AB  - One of the most widely cited cases of cultural transmission in animals is the
      opening of milk bottles by British birds. Bottle opening was first reported in
      Swaythling in 1921 and its spread from that date to 1947 was mapped by Fisher and
      Hinde (1949). Using data from Fisher and Hinde, this paper tests two quantitative
      models of cultural transmission: (1) the logistic model describing the cumulative
      number of bottle opening sites in the Belfast area and in the whole of the UK,
      and (2) the linear wave-of-advance model describing the progressive spread over
      time of bottle opening from its presumed single point of origin, Swaythling. For
      both the UK and Belfast, the logistic provides a poorer fit than alternative
      accelerating functions: the positive exponential and the reverse S-shaped
      hyperbolic sine respectively yield the best corrected fits to the Belfast and UK
      data. Neither functions have the terminal deceleration phase typical of the
      logistic, but both have an accelerating phase consistent with the cultural
      assumption of an auto-catalytic increase in the rate of spread over time. For
      both Belfast and the whole UK, the wave-of-advance model can clearly be rejected,
      even with the addition of a second source of innovation in County Durham. The
      results support the view that bottle opening originated from several independent
      sites, but spread through an accelerating process that could have included direct
      and/or indirect social influences. 

PMID- 24897248
TI  - Food preference behaviour of the five-striped squirrel, Funambulus pennanti
      Wroughton.
AB  - Food preference behaviour of Funambulus pennanti Wroughton was studied offering
      four different types of cereals, viz. wheat, millet, maize and rice in three
      textural forms, viz. whole dry, cracked and whole moist in no-choice, bi-choice
      and multiple-choice to the experimental squirrels. The mean daily intake of F.
      pennanti in no-choice has been recorded to be 3.53 to 11.70 g, which, however,
      increased to 6.31 to 14.19 g and 20.12 to 33.98 g in bi-choice and multiple
      choice experiments, respectively. The preference of squirrels in the no-choice
      feeding experiment was for cracked millet, whole moist wheat and whole dry wheat.
      In bi-choice feeding experiments, squirrels preferred cracked millet, whole moist
      millet and whole dry rice. In multiple-choice experiments, the squirrels showed a
      preference for cracked millet, whole moist and dry wheat and rice. On overall
      basis, cracked millet was highly preferred by the squirrels. In pen-feeding
      experiments where the squirrels were offered 12 different foods along with the
      different plant material including weeds, grasses, twigs of fruit trees, revealed
      the sustenance in preference of squirrels for cracked millet, whole moist millet,
      whole moist and dry wheat and whole dry rice in descending order. Squirrels
      neither formed any nest nor hoarded any food in the experimental pen. Squirrels
      did not reject any food during choice preference experiments and demonstrated
      optimal behaviour. Overall, squirrels exhibited a 'Generalist' feeding pattern.
      The present findings indicate that cracked millet should be used as a poison
      carrier for control of squirrels while other preferred cereals can also be used
      as a bait for mixing poison in the subsequent control operations. 

PMID- 24897249
TI  - Inter-individual associations and social structure of a mouflon population (Ovis
      orientalis musimon).
AB  - We analysed individual associations between mouflon (Ovis orientalis musimon)
      observed during one year in order to find ontogenetic patterns underlying the
      social structure of the population. A correspondence factorial analysis was
      performed on Simpson's coefficients to compare association profiles. No strong
      association was found between adults but some of the young adult females
      maintained a preferential bond with their mother until the age of three. Yearling
      males were firstly unstable in their social relations and subsequently developed
      a strong preference for peers (the preferred companion(s) of young adult males
      were always young adult males). Animals did not prefer to associate with other
      individuals of their own family (Wilcoxon test: n = 53; z = 0.463; a < 0.01).
      Localized abundant food sources caused large regroupings during spring. This was
      the only case where we noted a series of observations where the same unrelated
      animals were seen together. With the exception of the mother-offspring
      relationship, individual social preferences were based on the sex and age of the
      partner rather than on identity. The existence of social behaviour profiles
      dependent on sex and age is proposed to explain the above results. 

PMID- 24897250
TI  - Fear reactions of domestic sheep confronted with either a human or a human-like
      model.
AB  - Fear reactions of ewes towards a human, a human-like model or a control (plastic
      cylinder 1.95 m high) were studied using a test previously designed and
      validated, in which 16 behavioural parameters have been interpreted as indicators
      of fear (e.g. a relatively long time spent away from the stimulus) or absence of
      fear (e.g. a relatively long time spent eating near the stimulus). In a first
      experiment, 18 animals were individually confronted with each of the 3 stimuli
      for 4 min (in a counter-balanced order). The results indicated that both the
      human and the human-like model elicited greater fear reactions than did the
      control, and that the former two stimuli did not differ in their fear-eliciting
      properties. In a second experiment designed to determine if the animals become
      aware of a difference between the human and the model over time, 32 animals were
      confronted successively with each of the two stimuli for 8 min. Although there
      was some habituation towards both stimuli, there was no difference between them
      even at the end of the test period. These results suggest that a model could be
      appropriate in experiments involving human presence (at least for a short
      duration) and would allow for better standardization. It can also be hypothetized
      that exposing animals to a model would lead to familiarization which might in
      turn help reduce fear of human beings and thus improve ease of handling and
      welfare. 

PMID- 24897251
TI  - Predatory behaviour in females of two strains of mice selectively bred for
      isolation-induced intermale aggression.
AB  - The study sought to determine whether females of two strains of mice selectively
      bred for high (Turku Aggressive, TA) and low (Turku Non-Aggressive, TNA) levels
      of isolation-induced intermale aggression display differences in predatory
      behaviour. Additional subjects used in the study were females of the parental
      strain (Normal, N). Another aim of the present research was to investigate
      whether predatory aggression is associated with the postpartum period in the TA
      and TNA females. Testing consisted of dropping a live cricket into the home cage
      of the experimental females. The results showed that the predatory behaviour of
      individually housed TA and TNA females did not differ significantly. The only
      difference found between the two groups of females was in digging behaviour, the
      TA females showing more of this activity element on the first day of testing.
      Experience was found to affect the behaviour of the mice, attacking and consuming
      increased over trials whereas sniffing and the latency to attack decreased. In
      another experiment, TA and TNA females were tested for predatory aggression on
      the third day postpartum. The TA and TNA females were found to differ in all
      other observed behaviour variables but sniffing. The TA females spent more time
      chasing, tail-rattling, attacking, and consuming, as well as showing shorter
      latencies to the first attack. The TNA females spent more time digging, grooming,
      and nursing. The results suggest that the mechanisms determining the dispositions
      for predatory and maternal aggression in females and isolation induced intermale
      aggression and predatory aggression in males are not entirely different. 

PMID- 24897254
TI  - Statistical consideration and challenges in bridging study of personalized
      medicine.
AB  - Applications of personalized medicine are becoming increasingly prominent. A well
      characterized market-ready companion diagnostic assay (CDx) is often desired for
      patient enrollment in device-drug pivotal clinical trial(s) so that Food and Drug
      Administration can ensure that appropriate clinical and analytical validation
      studies are planned and carried out for CDx. However, such a requirement may be
      difficult or impractical to accomplish. A clinical trial assay (CTA) instead of
      CDx may be used for patient enrollment in the clinical trial. A concordance study
      (or bridging study) will be required to assess the agreement between CDx and CTA
      in order to bridge the clinical data (e.g. overall survival) from CTA to CDx and
      to evaluate the drug efficacy in CDx intended use population. In this article, we
      will discuss statistical challenges in study design and data analysis for
      bridging study. Particularly, we aimed to provide statistical methods on how to
      estimate the drug efficacy in CDx intended use population using results from
      bridging study and CTA-drug pivotal clinical trial. 

PMID- 24897255
TI  - Spatial organization of female groups in red deer (Cervus elaphus L.).
AB  - The spatial organization of female groups in red deer was studied in the periods
      before and after the rut, in a study area located in the central Sierra Morena
      (Cordoba, Spain). The study was carried out in terms of age-sex classes, and was
      based on direct observation and video recording. Movement order proved to be
      linear, and highlighted the role of the mature hind as group leader and potential
      group protector. Two tendencies were found in the calf: to place itself behind
      the adult female, and to take up a central position in the group. With regard to
      relationships of spatial proximity, the mature hind and the calf tended to keep
      separate from the rest of the group both in the period before and after the rut.
      The yearling male became progressively independent of the matriarchal group,
      tending in the second period of study to associate with individuals from its own
      age-sex class. 

PMID- 24897256
TI  - Responses to snake odors by laboratory mice.
AB  - Male and female laboratory mice (Mus musculus ; Harlan Sprague Dawley) were
      tested for reactions to snake odors. In the first experiment, mice were presented
      with untreated paper on the floor of one side of a test tank and snake-scented or
      control (water misted) paper on the other side. The scented papers were obtained
      from rough earth snakes (Virginia striatula ), which were fed earthworms, and a
      rat snake (Elaphe obsoleta ), which ate mice. Male mice exhibited no differences
      in response to the three conditions. Female mice showed no response to the
      control or earth snake odor, but they deposited significantly more fecal boli on
      the side of the tank with the rat snake odor than on the blank side. No
      significant differences in other behaviors, e.g. ambulation, were detected. In
      the second experiment, female mice were offered food pellets treated with the
      shed skin extract of the rat snake or with a solvent alone. Less material was bit
      off and consumed from the snake-scented pellets. The results of both experiments
      indicate that female mice detect the odors of rat snakes. 

PMID- 24897257
TI  - Instrumental performance following saccharin pre-feeding.
AB  - The effect of pre-feeding rats with a saccharin solution on instrumental
      performance, established with the same reinforcer, was studied in two
      experiments. Experiment 1 demonstrated that such pre-feeding depresses subsequent
      instrumental performance in an extinction test after training on a variable ratio
      schedule. In contrast, training on a variable interval schedule in Experiment 2
      rendered instrumental performance impervious to pre-feeding. The motivational
      effects of pre-feeding with a non-nutritive substance appear to act through an
      incentive rather than drive process. 

PMID- 24897258
TI  - The influence of cage size and environmental enrichment on the development of
      stereotypies in bank voles (Clethrionomys glareolus).
AB  - Bank voles were bred and lived in 4 different environments: small barren cages
      (SB), small enriched cages (SR), big barren cages (BB) and big enriched ones
      (BR). Ten different behaviours were recorded at the age of 30, 45, 60, 61, 75 and
      90 days. Between day 60 and 61, within each experimental environment, the group
      of voles performing stereotypies (ST) and the group of those which did not (NST)
      were each split in two, one part being transferred to a new environment, the
      other remaining in the same as control. For each of the 10 behaviours,
      differences between the 4 environments and therein differences between the ST and
      the NST animals and between the age groups were analysed with a split-plot ANOVA.
      The results indicated that enrichment is more determinant than cage size, as more
      voles developed stereotypies in SB and BB than in SR and BR. Improving the
      environment after day 60 inhibited the stereotypies in most ST animals, while
      smaller and/or barren environments elicited them in very few NST. ST voles
      performed significantly more rearing and walking-sniffing and showed
      significantly less immobility than NST ones. These differences remained linked to
      the ST/NST status when an animal reversed it after day 60. Within different
      environments, some individuals are more prone to react actively to frustration,
      including the development of stereotypies. The performance of stereotypies is
      associated with a more general behavioural activation. 

PMID- 24897259
TI  - Effect of conspecific urine odour on behaviour of soft-furred field-rat, Rattus
      meltada.
AB  - Given a choice to feed on millet in two separate food baskets placed on two sides
      of the cage, the soft-furred field-rat, Rattus meltada pallidior preferred millet
      in which 1% conspecific urine, either of male or female, was added indicating the
      conspecific urine or its odour functions as phagostimulant for this rodent.
      Evaluation of the responses of male and female metads towards the urine odour of
      the either sex revealed that they prefer uni-sex odour. Both the sexes of field
      rat stayed in the urine side of the cage for a longer duration (P < 0.001) and
      the males sebum-marked and the females urine-marked with a higher frequency in
      the urine environment as compared to the other side of the cage. 

PMID- 24897260
TI  - Developpement de la locomotion chez le mulot sylvestre (Apodemus sylvaticus L.).
AB  - This longitudinal study describes the functional development of locomotion in the
      woodmouse, Apodemus sylvaticus . It shows that postnatal day (PND) 11 is a
      critical age in the acquisition of independence. Locomotion develops in
      successive stages before reaching the adult pattern (walking) at PND 11.
      Intermediate patterns are determined by the degree of coordination between the
      different parts of the body. Some of these patterns overlap and do not
      necessarily appear in every individual in our experiments. The young woodmouse
      respond optimally in three sensorimotor tests on PND 10 (contact righting,
      negative geotaxis) and on PND 11 (cliff avoidance). Immature reflexes, which may
      have specific functions in a short period of the early development have then
      disappeared. Simultaneously, there is a transition from stereotyped to oriented
      reactions (exploration, flight, etc.) which depend more and more on nonspecific
      stimulations (manipulation, etc.) rather than on specific ones (slope, cliff).
      These decisive changes are accomplished two days before eye opening. We can
      parallel them to the drastic ones that we reported elsewhere in the production of
      ultrasonic vocalisations. These signals elicit the retrieval of the pups by the
      mother, thereby compensating for the incapacity of the pup to move in an
      organised way. This study gives a basis for comparisons with other Rodents. In
      general, the woodmouse matures earlier than the rat by about two days, but later
      than the housemouse by two days. However, this delay might vary according to the
      given task. We discuss our results from a methodological point of view, and
      underline the advantages of measuring a continuous variable against an arbitrary
      criterion. 

PMID- 24897261
TI  - Brain monoamines and sexual behavior in Japanese quail: Effects of castration and
      steroid replacement therapy.
AB  - In the male Japanese quail, testosterone is required for the activation of sexual
      behavior. This steroid dependent process may rely heavily on mediation via
      monoaminergic neurons. These experiments were conducted to study the relationship
      between reproductive state (hormonal and behavioral components) and levels of
      monoamines in selected areas of the brain in Japanese quail. In Experiment 1,
      monoamine levels in a number of brain areas were compared in castrates,
      testosterone-implanted castrates, and intact males. Monoamine levels were
      comparable to those previously measured in Japanese quail, and there were no
      significant differences due to treatment. Plasma luteinizing hormone (LH) levels
      and recovery of cloacal gland area in implanted castrates confirmed the afficacy
      of treatments. In Experiment 2, the disappearance of dopamine (DA) and
      norepinephrine (NE) following administration of a-methyl-para-tyrosine (aMPT) was
      used as an indicator of turnover rate. Male and female quail were gonadectomized
      at 3 weeks of age. At the age of five weeks, some gonadectomized males and
      females were given implants containing testosterone. Only intact males and
      testosterone-implanted castrated males showed reproductive behavior. Plasma
      gonadotropin levels were elevated in gonadectomized birds and reduced in steroid
      implanted gonadectomized birds. The aMPT treatment significantly reduced the
      levels of DA and NE in the telecephalon and the level of DA in the hypothalamus.
      After aMPT treatment, the disappearance of NE in the telecephalon and of DA in
      the hypothalamus were significantly different according to the sex or treatment
      of the birds or both. Significant interactions between these two factors were
      observed. Disappearance rate of NE in the telecephalon was decreased by
      castration of males and increased by ovariectomy of females. Both effects were
      counteracted by testosterone. Reverse effects were observed for DA disappearance
      in the hypothalamus (increase with castration in males and decrease with
      ovariectomy in females). These results give evidence for altered aminergic
      function in specific areas of the brain relative to altered reproductive state. 

PMID- 24897262
TI  - Temporal pattern of exploratory behavior during 24-hour sessions in a Japanese
      monkey (Macaca fuscata) troop.
AB  - The temporal pattern of exploratory behavior of a troop of Japanese monkeys to a
      novel apparatus introduced into their habitat was examined during four successive
      24-hour periods. An "exploratory behavior" was defined as a press to a
      transilluminated panel within the apparatus. These presses had no scheduled
      consequences. The results showed that: (1) there was no responding from 1900 to
      0600 hours; and (2) that day-time responding was bimodal, with activity peaking
      between 1000 and 1100, and 1600 and 1700 hours. These findings were discussed in
      terms of field studies and operant-based research which have studied diurnal
      processes in monkeys. 

PMID- 24897263
TI  - Influence of odours of male organ homogenates on maturation of young female
      meadow voles, Microtus pennsylvanicus.
AB  - Female meadow vole weanlings exposed to odours from homogenates of bladder and
      testis taken from sexually mature males showed more rapid maturation (earlier
      vaginal perforation, heavier uteri, adrenal glands, and ovaries with more and
      larger Graafian follicles, and cornified smears lacking mucus) than controls
      exposed to distilled water. Females exposed to kidney homogenates showed similar
      responses except that their time of vaginal perforation and adrenal weight did
      not differ from controls, and some had mucous smears. Seminal vesicle, preputial,
      and prostate homogenates produced only occasional effects on these indicators of
      reproductive maturation. The pheromone responsible for these effects, known to be
      present in urine, is deduced to enter the urine stream at the kidney rather than
      at the level of the sexual accessories. 

PMID- 24897278
TI  - Pharmacogenetics of smoking: how far to the clinic?

PMID- 24897276
TI  - Role of protease-activated receptor 2 in lung injury development during acute
      pancreatitis in rats.
AB  - OBJECTIVE: The objective of this study was to evaluate whether an uncontrolled
      activation of mast cells and macrophages through protease-activated receptor-2
      (PAR-2) during acute pancreatitis could develop lung injury. METHODS:
      Pancreatitis was induced in rats by intraductal infusion of sodium taurocholate.
      In a group of animals, PAR-2 antagonist or trypsin (TRP) inhibitor was
      intravenously administered before the pancreatitis induction. In additional
      groups, the animals were treated with PAR-2-activating peptide or pancreatic TRP.
      The myeloperoxidase (MPO) activity was measured to evaluate the progression of
      inflammation. RESULTS: Plasma from the animals with pancreatitis and pancreatic
      TRP induced the secretion of mast cells and alveolar macrophages as well as
      increased the density of PAR-2 in the plasma membrane. The treatment of alveolar
      macrophages with TRP, tryptase, as well as PAR-1- and PAR-2-activating peptide
      led to an increase in calcium-triggered exocytosis. Similar results were obtained
      in acinar cells. The intravenous injection of PAR-2-activating peptide and TRP
      induced an increase in MPO activity in the lung. The intravenous injection of PAR
      2 antagonist or TRP inhibitor before the pancreatitis induction could prevent the
      increase in MPO activity in the pancreas and the lung. CONCLUSIONS: The TRP
      generated during acute pancreatitis could be involved in the progression of lung
      injury through the activation of PAR-2 in alveolar macrophages.

PMID- 24897279
TI  - Cost-effectiveness of genotyping to guide treatment.

PMID- 24897277
TI  - Warfarin pharmacogenetic trials: is there a future for pharmacogenetic-guided
      dosing?

PMID- 24897280
TI  - Pharmacogenomics failing to reach developing countries.

PMID- 24897281
TI  - Research highlights: highlights from the latest articles on the pharmacogenomics
      of neuropsychiatric disorders.

PMID- 24897282
TI  - Conference scene: pharmacogenomics: from cell to clinic (part 2).
AB  - Second International ESPT Meeting Lisbon, Portugal, 26-28 September 2013 The
      second European Society of Pharmacogenomics and Theranostics (ESPT) conference
      was organized in Lisbon, Portugal, and attracted 250 participants from 37
      different countries. The participants could listen to 50 oral presentations,
      participate in five lunch symposia and were able to view 83 posters and an
      exhibition. Part 1 of this Conference Scene was presented in the previous issue
      of Pharmacogenomics. This second part will focus on: clinical implementation of
      pharmacogenomics tests; transporters and pharmacogenomics; stem cells and other
      new tools for pharmacogenomics and drug discovery; from system pharmacogenomics
      to personalized medicine; and, finally, we will discuss the Posters and Awards
      that were presented at the conference. 

PMID- 24897283
TI  - Interindividual variability in TPMT enzyme activity: 10 years of experience with
      thiopurine pharmacogenetics and therapeutic drug monitoring.
AB  - BACKGROUND & AIMS: TPMT activity and metabolite determination (6-thioguanine
      nucleotides [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) remain
      controversial during thiopurine management. This study assessed associations
      between patient characteristics and TPMT activity, and their impact on metabolite
      levels. PATIENTS & METHODS: A retrospective review of the laboratory database
      from a French university hospital identified 7360 patients referred for TPMT
      phenotype/genotype determination, and/or for 6-TGN/6-MMPN monitoring. RESULTS:
      Four TPMT phenotypes were identified according to TPMT activity distribution:
      low, intermediate, normal/high and very high. Based on 6775 assays, 6-TGN
      concentrations were 1.6-fold higher in TPMT-deficient patients compared with TPMT
      normal patients. Azathioprine dose and TPMT genotype were significant predictors
      of metabolite levels. Furthermore, 6-MMPN and 6-MMPN: 6-TGN ratios were,
      respectively, 1.6- and 2.2-fold higher in females than in males, despite similar
      TPMT, 6-TGN and azathioprine doses. An unfavorable ratio (>=20) was associated
      with a slightly higher TPMT activity. CONCLUSION: These results illustrate the
      usefulness of pharmacogenomics and metabolite measurement to improve the
      identification of noncompliance and patients at high risk for toxicity or
      therapeutic resistance. Original submitted 13 November 2013; Revision submitted
      30 January 2014.

PMID- 24897285
TI  - nNOS polymorphisms are associated with responsiveness to sildenafil in clinical
      and postoperative erectile dysfunction.
AB  - AIM: Sildenafil potentiates the nitric oxide (NO) signaling pathway. Since
      neuronal NOS is very important in the penis, we assessed whether NOS1
      polymorphisms are associated with altered responsiveness to sildenafil in
      erectile dysfunction (ED). MATERIALS & METHODS: Patients (n = 137) were divided
      as clinical ED or postoperative ED. They were subdivided as good responders or
      poor responders to sildenafil, and genotypes for rs41279104 and rs2682826 NOS1
      polymorphisms were determined. RESULTS: We found that the rs41279104 CT genotype
      was associated with good responders in postoperative ED patients, while rs2682826
      CT genotype was associated with good responders in postoperative ED, and the TT
      genotype associated with good responders in both groups. Finally, the CT
      haplotype was associated with good responders in postoperative ED. CONCLUSION:
      NOS1 polymorphisms are associated with responsiveness to sildenafil in ED.
      Original submitted 20 November 2013; Revision submitted 31 January 2014.

PMID- 24897286
TI  - Association analysis of UGT1A genotype and haplotype with SN-38 glucuronidation
      in human livers.
AB  - AIM: 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan,
      is mainly eliminated hepatically through glucuronidation by UGT1A1 and UGT1A9
      enzymes. This study comprehensively investigates the effects of UGT1A1 and UGT1A9
      genetic polymorphism on SN-38 glucuronidation activity. MATERIALS & METHODS:
      Genetic polymorphisms and combinational haplotypes of UGT1A1 and UGT1A9, SN-38
      glucuronidation activities, and protein levels of UGT1A1 and UGT1A9 were
      determined using a set of over 45 Chinese livers. RESULTS: UGT1A1 reduced
      function variants UGT1A1*6, *28, *60 and *1B exhibited additive effect. The
      number of UGT1A1 reduced function alleles was associated with decreased SN-38G
      formation rates and UGT1A protein levels. UGT1A9 I399C>T and UGT1A9*1b, which
      were highly linked, were associated with increased SN-38 glucuronidation activity
      and UGT1A protein levels. However, further analysis based on UGT1A9-1A1
      haplotypes confirmed that their increased effect was partly due to their close
      linkage with UGT1A1 reduced function alleles. CONCLUSION: UGT1A1 genetic
      polymorphisms have a more important function in human liver SN-38 glucuronidation
      activity than UGT1A9. Original submitted 7 November 2013; Revision submitted 30
      January 2014.

PMID- 24897284
TI  - Developmental and extracellular matrix-remodeling processes in rosiglitazone
      exposed neonatal rat cardiomyocytes.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of
      rosiglitazone (Avandia((r))) on gene expression in neonatal rat ventricular
      myocytes. MATERIALS & METHODS: Myocytes were exposed to rosiglitazone ex vivo.
      The two factors examined in the experiment were drug exposure (rosiglitazone and
      dimethyl sulfoxide vs dimethyl sulfoxide), and length of exposure to drug (1/2 h,
      1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h, 36 h and 48 h). RESULTS: Transcripts
      that were consistently expressed in response to the drug were identified.
      Cardiovascular system development, extracellular matrix and immune response are
      represented prominently among the significantly modified gene ontology terms.
      CONCLUSION: Hmgcs2, Angptl4, Cpt1a, Cyp1b1, Ech1 and Nqo1 mRNAs were strongly
      upregulated in cells exposed to rosiglitazone. Enrichment of transcripts involved
      in cardiac muscle cell differentiation and the extracellular matrix provides a
      panel of biomarkers for further analysis in the context of adverse cardiac
      outcomes in humans. Original submitted 15 November 2013; Revision submitted 14
      February 2014.

PMID- 24897287
TI  - Pharmacogenetic analysis of GLCCI1 in three north European pediatric asthma
      populations with a reported use of inhaled corticosteroids.
AB  - BACKGROUND: GLCCI1 rs37972 has previously been associated with decreased lung
      function improvement upon treatment with inhaled corticosteroids (ICS) in
      asthmatics. AIM: To assess whether variation in rs37972 is associated with
      altered ICS efficacy in north European asthmatic children and young adults with a
      reported use of ICS. PATIENTS & METHODS: rs37972 was genotyped in three cohort
      studies of asthmatic children with a reported use of ICS. As an indicator for
      asthma exacerbations, asthma-related hospital visits and oral corticosteroid use
      were studied. Asthma control was assessed using a questionnaire. RESULTS: rs37972
      T allele was not significantly associated with an increased risk of oral
      corticosteroid use (summary odds ratio: 1.20; 95% CI: 0.99-1.45), an increased
      risk of asthma-related hospital visits (summary odds ratio: 1.07; 95% CI: 0.89
      1.29), uncontrolled symptoms (summary odds ratio: 1.01; 95% CI: 0.75-1.36) or
      higher ICS dosages (summary beta: 0.01, 95% CI: -0.06-0.08). CONCLUSION:
      Variation in GLCCI1 rs37972 genotype does not seem to affect ICS efficacy in
      north European asthmatic children. Original submitted 26 November 2013; Revision
      submitted 13 February 2014.

PMID- 24897288
TI  - LRP5 polymorphisms and response to alendronate treatment in Chinese
      postmenopausal women with osteoporosis.
AB  - AIM: To investigate the association between LRP5 gene polymorphisms and response
      to alendronate in Chinese osteoporotic women. MATERIALS & METHODS: Six hundred
      and thirty nine Chinese postmenopausal women with osteopenia or osteoporosis were
      included and received alendronate treatment. The A1330V polymorphism of LRP5 was
      investigated. Bone mineral density (BMD) and bone turnover markers (ALP and beta
      isomerized carboxy-telopeptide of type I collagen [beta-CTX]) were measured
      before and after treatment. The correlation of LRP5 polymorphisms with changes in
      BMD and bone turnover biomarkers were analyzed after treatment. RESULTS: After 12
      months of treatment, participants with CC and CT genotypes had a larger increase
      in lumbar spine BMD and a larger decrease in serum beta-CTX and ALP levels than
      those with TT genotype (all p < 0.001). No significant genotype-treatment
      interaction was found in hip BMD. CONCLUSION: The A1330V polymorphism of LRP5 is
      possibly correlated with response to alendronate treatment in Chinese women with
      osteoporosis, and the TT genotype could possibly predict a weak response to
      alendronate.

PMID- 24897290
TI  - Pharmacogenovigilance: a pharmacogenomics pharmacovigilance program.
AB  - In this report, we review the importance of pharmacovigilance in detecting
      postmarketing adverse drug events and the potential for developing
      pharmacogenovigilance programs by integrating pharmacogenomics with
      pharmacovigilance. We propose to start developing such a program in primary
      healthcare systems that use basic features of electronic medical records and have
      access to large numbers of patients commonly prescribed drugs. Such programs, if
      carefully designed, may grow over time and hopefully enhance the collection and
      interpretation of useful data for the clinical applications of pharmacogenomics
      testing. 

PMID- 24897289
TI  - Evaluation of clinical and genetic indicators for the early response to
      intravitreal ranibizumab in exudative age-related macular degeneration.
AB  - AIM: This study was conducted to evaluate the possible clinical and genetic
      indicators for an early response to intravitreal ranibizumab (IVR) in exudative
      age-related macular degeneration (AMD). PATIENTS & METHODS: The records of 120
      eyes from 120 Japanese patients with treatment-naive exudative AMD were
      retrospectively reviewed. Three consecutive IVR treatments were performed every
      month. Achievement of anatomical resolution was evaluated by ophthalmoscopy and
      optical coherence tomography. Multivariable logistic regression analysis was
      conducted by analyzing SNPs in the ARMS2 locus (A69S) and in the CFH gene (I62V
      and Y402H), in addition to clinical factors. RESULTS: The mean central retinal
      thickness of overall patients was significantly decreased (-120.1 +/- 122.8 um, p
      = 2.7 * 10(-19)) at 3 months after the initial treatment. In the logistic
      regression analysis, the poor anatomical resolution of the lesion at 3 months was
      associated with the combination of CFH I62V + CFH Y402H variants (p = 0.0021),
      and the polypoidal choroidal vasculopathy lesions (p = 0.044). CONCLUSION: The
      CFH variants and the polypoidal choroidal vasculopathy lesion may influence the
      early anatomical resolution with IVR in exudative AMD.

PMID- 24897291
TI  - Pharmacogenetics of antiepileptic drug-induced hypersensitivity.
AB  - Antiepileptic drugs can induce potentially life-threatening hypersensitivity
      reactions such as Stevens-Johnson syndrome at a frequency of one in 10,000 to one
      in 1000 treated patients. There is a considerable cross-reactivity among
      different antiepileptic drugs but the mechanisms are not known. In this review we
      have summarized current evidence on antiepileptic drug-induced hypersensitivity
      reactions and performed meta-analyses of published case-control studies that
      investigated associations between HLA alleles and several antiepileptic drugs in
      diverse populations. As the heterogeneity between studies was high, we conducted
      subsequent subgroup analyses and showed that HLA-B*15:02 was associated with
      carbamazepine, lamotrigine and phenytoin-induced Stevens-Johnson syndrome in
      Asian populations indicating that pretreatment testing may prevent cross
      reactivity. Additionally, we explored the potential of new, high-throughput
      technologies that may help to understand the mechanisms and predict the risk of
      adverse drug reactions in the future. 

PMID- 24897292
TI  - Pharmacogenetics of second-generation antipsychotics.
AB  - This review considers pharmacogenetics of the so called 'second-generation'
      antipsychotics. Findings for polymorphisms replicating in more than one study are
      emphasized and compared and contrasted with larger-scale candidate gene studies
      and genome-wide association study analyses. Variants in three types of genes are
      discussed: pharmacokinetic genes associated with drug metabolism and disposition,
      pharmacodynamic genes encoding drug targets, and pharmacotypic genes impacting
      disease presentation and subtype. Among pharmacokinetic markers, CYP2D6
      metabolizer phenotype has clear clinical significance, as it impacts dosing
      considerations for aripiprazole, iloperidone and risperidone, and variants of the
      ABCB1 gene hold promise as biomarkers for dosing for olanzapine and clozapine.
      Among pharmacodynamic variants, the TaqIA1 allele of the DRD2 gene, the DRD3
      (Ser9Gly) polymorphism, and the HTR2C -759C/T polymorphism have emerged as
      potential biomarkers for response and/or side effects. However, large-scale
      candidate gene studies and genome-wide association studies indicate that
      pharmacotypic genes may ultimately prove to be the richest source of biomarkers
      for response and side effect profiles for second-generation antipsychotics. 

PMID- 24897293
TI  - Pharmacogenetics of ovarian response.
AB  - Effective controlled ovarian stimulation (COS) is crucial for IVF outcome.
      Ovarian response to follicle-stimulating hormone, however, varies widely among
      women undergoing ovarian stimulation. Advance identification of patients who will
      elicit a poor or high response to standard treatment would be of great clinical
      benefit for such patients. Application of pharmacogenetics to ovarian response
      may predict stimulation success but also help in the adjustment and design of
      doses prior to treatment. Different studies have examined the impact of
      variations in follicle-stimulating hormone receptor, biochemical pathways
      involved in estrogen production and action, folliculogenesis and other aspects.
      Recently, gene-association studies have tried to identify a number of genetic
      variations affecting interindividual variability in COS. 

PMID- 24897294
TI  - Catalytic asymmetric total synthesis of (+)-caprazol.
AB  - Catalytic asymmetric total synthesis of caprazol, a lipo-nucleoside antibiotic,
      has been accomplished employing two of the stereoselective C-C bond forming
      reactions as key transformations. The stereochemistries of the beta-hydroxy-alpha
      aminoester moiety at the juncture of the uridine part and diazepanone part, and
      of the beta-hydroxy-alpha-amino acid moiety embedded in the diazepanone system,
      were constructed using a diastereoselective isocyanoacetate aldol reaction (dr =
      88:12) and an enantioselective anti-nitroaldol reaction catalyzed by a Nd/Na
      chiral amide ligand (dr = 12:1, 95% ee), respectively. 

PMID- 24897295
TI  - Comprehensive secondary structure elucidation of four genera of the family
      Pospiviroidae.
AB  - Viroids are small, circular, single stranded RNA molecules that infect plants.
      Since they are non-coding, their structures play a critical role in their life
      cycles. To date, little effort has been spend on elucidating viroid structures in
      solution due to both the experimental difficulties and the time-consuming nature
      of the methodologies implicated. Recently, the technique of high-throughput
      selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) was adapted
      for the probing of the members of family Avsunviroidae, all of whom replicate in
      the chloroplast and demonstrate ribozyme activity. In the present work, twelve
      viroid species belonging to four different genera of the family Pospiviroidae,
      whose members are characterized by the presence of a central conserved region
      (CCR) and who replicate in nucleus of the host, were probed. Given that the
      structures of five distinct viroid species from the family Pospiviroidae have
      been previously reported, an overview of the different structural characteristics
      for all genera and the beginning of a manual classification of the different
      viroids based on their structural features are presented here. 

PMID- 24897297
TI  - In situ infrared study of the effect of amine density on the nature of adsorbed
      CO2 on amine-functionalized solid sorbents.
AB  - In situ Fourier transform infrared spectroscopy was used to determine the nature
      of adsorbed CO2 on class I (amine-impregnated) and class II (amine-grafted)
      sorbents with different amine densities. Adsorbed CO2 on amine sorbents exists in
      the form of carbamate-ammonium ion pairs, carbamate-ammonium zwitterions, and
      carbamic acid. The adsorbed CO2 on high-amine density sorbents showed that the
      formation of ammonium ions correlates with the suppression of CH stretching
      intensities. An HCl probing technique was used to resolve the characteristic
      infrared bands of ammonium ions, clarifying that the band observed around 1498
      cm(-1) is a combination of the deformation vibration of ammonium ion (NH3(+)) at
      1508 and 1469 cm(-1) and the deformation vibration of NH in carbamate (NHCOO(-))
      at 1480 cm(-1). Carbamate and carbamic acid on sorbents with low amine density
      desorbed at a rate faster than those on sorbents with high amine density after
      switching the flow from CO2 to Ar at 55  degrees C. Evaluation of the desorption
      temperature profiles showed that the temperature required to achieve the maximal
      desorption of CO2 (Tmax. des) increases with amine density. The adsorbed CO2 on
      sorbents with high amine density is stabilized via hydrogen bonding interactions
      with adjacent amine sites. These sorbents require higher temperature to desorb
      CO2 than those with low amine density. 

PMID- 24897296
TI  - Saccharin derivatives as inhibitors of interferon-mediated inflammation.
AB  - A series of novel, saccharin-based antagonists have been identified for the
      interferon signaling pathway. Through in vitro high-throughput screening with the
      Colorado Center for Drug Discovery (C2D2) Pilot Library, we identified hit
      compound 1, which was the basis for extensive structure-activity relationship
      studies. Our efforts produced a lead anti-inflammatory compound, tert-butyl N
      (furan-2-ylmethyl)-N-{4-[(1,1,3-trioxo-2,3-dihydro-1lambda(6),2-benzothiazol-2
      yl)methyl]benzoyl}carbamate CU-CPD103 (103), as a potent inhibitor using an
      established nitric oxide (NO) signaling assay. With further studies of its
      inhibitory mechanisms, we demonstrated that 103 carries out this inhibition
      through the JAK/STAT1 pathway, providing a drug-like small molecule inflammation
      suppressant for possible therapeutic uses.

PMID- 24897298
TI  - Edaravone protect against retinal damage in streptozotocin-induced diabetic mice.
AB  - Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is
      used for the clinical treatment of retinal injury. In this study, we investigated
      the protective effects of edaravone against diabetic retinal damage in the mouse.
      Diabetic retinopathy in the mouse was induced by injection of streptozotocin.
      Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose
      of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes.
      Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern
      electroretinogram (ERG). RGCs damage was also detected by Terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the
      levels of reactive oxygen species (ROS) were determined fluorometrically. The
      expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by
      Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved
      caspase-3 were significantly increased, whereas the expression of BDNF was
      significantly decreased in the retinas of diabetic mice, compared to nondiabetic
      mice. Administration of edaravone significantly attenuated diabetes induced RGCs
      death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and
      downregulation of BDNF. These findings suggest that oxidative stress plays a
      pivotal role in diabetic retinal damage and that systemic administration of
      edaravone may slow the progression of retinal neuropathy induced by diabetes. 

PMID- 24897300
TI  - Having a say matters: influence of decision-making power on contraceptive use
      among Nigerian women ages 35-49 years.
AB  - BACKGROUND: Research suggests that women of reproductive age who are involved in
      household decision-making are more likely than those who are not involved to be
      able to control their fertility. Little is known, however, about this
      relationship among women at the upper end of the reproductive spectrum. The aim
      of this study was to determine the association between household decision-making
      power and modern contraceptive use among Nigerian women ages 35-49 years.
      METHODS: A descriptive, cross-sectional study involving a secondary analysis of
      data from the Nigerian 2008 Demographic and Health Survey was conducted among
      women ages 35-49 years who were considered to be in need of contraception. The
      outcome was modern contraceptive use while the main independent variable was a
      woman's household decision-making power score, constructed using principal
      component analysis. Multivariate logistic regression was performed to determine
      whether the women's household decision-making power score, categorized into
      tertiles, was independently associated with modern contraceptive use. Data were
      weighted and adjusted for the complex survey design. RESULTS: Prevalence of
      modern contraceptive use among Nigerian women deemed to be in need of
      contraception in this study was 18.7%. Multivariate logistic regression showed
      that women's decision-making power remained statistically significantly
      associated with modern contraceptive use, even after adjusting for age,
      education, religion, polygyny, parity, wealth and domicile. Women who were in the
      highest decision-making power tertile had more than one and a half times the odds
      of using modern contraception compared with women in the lowest tertile [Adjusted
      Odds Ratio = 1.70; 95% Confidence Interval = 1.31-2.21, p<0.001]. SIGNIFICANCE:
      Older Nigerian women who are involved in making household decisions are also able
      to make decisions related to their fertility. Programs in Nigeria focused on
      increasing modern contraceptive use should include strategies to increase women's
      status through encouraging more visible involvement in decision-making across
      different spheres of their lives.

PMID- 24897299
TI  - Silver sucrose octasulfate (IASOSTM) as a valid active ingredient into a novel
      vaginal gel against human vaginal pathogens: in vitro antimicrobial activity
      assessment.
AB  - This in vitro study assessed the antimicrobial properties of a novel octasilver
      salt of Sucrose Octasulfate (IASOS) as well as of an innovative vaginal gel
      containing IASOS (SilSOS Femme), against bacterial and yeast pathogens isolated
      from human clinical cases of symptomatic vaginal infections. In BHI and LAPT
      culture media, different ionic silver concentrations and different pHs were
      tested. IASOS exerted a strong antimicrobial activity towards all the pathogens
      tested in both culture media. The results demonstrated that salts and organic
      compounds present in the culture media influenced IASOS efficacy only to a
      moderate extent. Whereas comparable MBCs (Minimal Bactericidal Concentrations)
      were observed for G. vaginalis (10 mg/L Ag+), E. coli and E. aerogenes (25 mg/L
      Ag+) in both media, higher MBCs were found for S. aureus and S. agalactiae in
      LAPT cultures (50 mg/L Ag+ versus 25 mg/L Ag+). No minimal concentration totally
      inhibiting the growth of C. albicans was found. Nevertheless, in both media at
      the highest ionic silver concentrations (50-200 mg/L Ag+), a significant 34-52%
      drop in Candida growth was observed. pH differently affected the antimicrobial
      properties of IASOS against bacteria or yeasts; however, a stronger antimicrobial
      activity at pH higher than the physiological pH was generally observed. It can be
      therefore concluded that IASOS exerts a bactericidal action against all the
      tested bacteria and a clear fungistatic action against C. albicans. The
      antimicrobial activity of the whole vaginal gel SilSOS Femme further confirmed
      the antimicrobial activity of IASOS. Overall, our findings support IASOS as a
      valid active ingredient into a vaginal gel. 

PMID- 24897302
TI  - Four-coordinate cobalt pincer complexes: electronic structure studies and ligand
      modification by homolytic and heterolytic pathways.
AB  - A family of cobalt chloride, methyl, acetylide and hydride complexes bearing both
      intact and modified tert-butyl substituted bis(phosphino)pyridine pincer ligands
      has been synthesized and structurally characterized and their electronic
      structures evaluated. Treatment of the unmodified compounds with the stable
      nitroxyl radical, TEMPO (2,2,6,6-tetramethylpiperidin-1-yloxidanyl) resulted in
      immediate H- atom abstraction from the benzylic position of the chelate yielding
      the corresponding modified pincer complexes, ((tBu)mPNP)CoX (X = H, CH3, Cl,
      CCPh). Thermolysis of the methyl and hydride derivatives, ((tBu)PNP)CoCH3 and
      ((tBu)PNP)CoH, at 110  degrees C also resulted in pincer modification by H atom
      loss while the chloride and acetylide derivatives proved inert. The relative
      ordering of benzylic C-H bond strengths was corroborated by H atom exchange
      experiments between appropriate intact and modified pincer complexes. The
      electronic structures of the modified compounds, ((tBu)mPNP)CoX were established
      by EPR spectroscopy and DFT computations and are best described as low spin
      Co(II) complexes with no evidence for ligand centered radicals. The electronic
      structures of the intact complexes, ((tBu)PNP)CoX were studied computationally
      and bond dissociation free energies of the benzylic C-H bonds were correlated to
      the identity of the X-type ligand on cobalt where pure sigma donors such as
      hydride and methyl produce the weakest C-H bonds. Comparison to a rhodium
      congener highlights the impact of the energetically accessible one-electron redox
      couple of the first row metal ion in generating weak C-H bonds in remote
      positions of the supporting pincer ligand. 

PMID- 24897301
TI  - CXCL16 and CXCR6 are coexpressed in human lung cancer in vivo and mediate the
      invasion of lung cancer cell lines in vitro.
AB  - Despite advances in early diagnosis and multimodality therapy for cancers, most
      of lung cancer patients have been locally advanced or metastatic at the time of
      diagnosis, suggesting the highly progressive characteristic of lung cancer cells.
      The mechanisms underling invasiveness and metastasis of lung cancer are yet to be
      elucidated. In the present study, immunohistochemistry was performed to detect
      the expression of CXCL16-CXCR6 in human lung cancer tissues. It was demonstrated
      that similar to CXCL12 and CXCR4, CXCL16 and CXCR6 were also coexpressed in human
      primary lung cancer tissues. After confirming the functional existence of CXCL16
      and CXCR6 protein in A549, 95D and H292 cells by ELSA and flow cytometry
      analysis, we further explored the significance of CXCL16-CXCR6 axis in the
      biological functions of lung cancer cell lines in vitro. It was found that CXCL16
      had no effects on the PCNA (proliferating cell nuclear antigen) expression of
      A549, 95D and H292 cells. However, both exogenous CXCL16 and CM (conditioned
      medium from A549, 95D or H292) significantly improved the in vitro viability and
      invasion of three lung cancer cell lines. The neutralizing antibody to CXCL16 or
      down-regulation of CXCR6 was able to inhibit the increased viability and
      invasiveness of A549, 95D and H292 cells stimulated by CXCL16 or CM. Our results
      imply that CXCL16-CXCR6 axis is involved in the regulation of viability and
      invasion rather than PCNA expression of lung caner cells, which opens the door
      for better understanding the mechanisms of lung tumor progression and metastasis.

PMID- 24897303
TI  - The basics and advances of immunomodulators and antigen presentation: a key to
      development of potent memory response against pathogens.
AB  - INTRODUCTION: Immunomodulators are agents, which can modulate the immune response
      to specific antigens, while causing least toxicity to the host system. Being part
      of the modern vaccine formulations, these compounds have contributed remarkably
      to the field of therapeutics. Despite the successful record maintained by these
      agents, the requirement of novel immunomodulators keeps increasing due to the
      increasing severity of diseases. Hence, research regarding the same holds great
      importance. AREAS COVERED: In this review, we discuss the role of
      immunomodulators in improving performance of various vaccines used for
      counteracting most threatening infectious diseases, mechanisms behind their
      action and criteria for development of novel immunomodulators. EXPERT OPINION:
      Understanding the molecular mechanisms underlying immune response is a
      prerequisite for development of effective therapeutics as these are often
      exploited by pathogens for their own propagation. Keeping this in mind, the
      present research in the field of immunotherapy focuses on developing
      immunomodulators that would not only enhance the protection against pathogen, but
      also generate a long-term memory response. With the introduction of advanced
      formulations including combination of different kinds of immunomodulators, one
      can expect tremendous success in near future.

PMID- 24897304
TI  - Enhancing the Biological Relevance of Secretome-Based Proteomics by Linking Tumor
      Cell Proliferation and Protein Secretion.
AB  - Secretome profiling has become a methodology of choice for the identification of
      tumor biomarkers. We hypothesized that due to the dynamic nature of secretomes
      cellular perturbations could affect their composition but also change the global
      amount of protein secreted per cell. We confirmed our hypothesis by measuring the
      levels of secreted proteins taking into account the amount of proteome produced
      per cell. Then, we established a correlation between cell proliferation and
      protein secretion that explained the observed changes in global protein
      secretion. Next, we implemented a normalization correcting the statistical
      results of secretome studies by the global protein secretion of cells into a
      generalized linear model (GLM). The application of the normalization to two
      biological perturbations on tumor cells resulted in drastic changes in the list
      of statistically significant proteins. Furthermore, we found that known
      epithelial-to-mesenchymal transition (EMT) effectors were only statistically
      significant when the normalization was applied. Therefore, the normalization
      proposed here increases the sensitivity of statistical tests by increasing the
      number of true-positives. From an oncology perspective, the correlation between
      protein secretion and cellular proliferation suggests that slow-growing tumors
      could have high-protein secretion rates and consequently contribute strongly to
      tumor paracrine signaling.

PMID- 24897305
TI  - Pre-task prefrontal activation during cognitive processes in aging: a near
      infrared spectroscopy study.
AB  - PURPOSE: Cognitive processing generally deteriorates as people age. Recent
      neuroimaging studies have shown that the prefrontal cortex (PFC) is involved in
      human-specific behavior, such as preparing for future actions and prospective
      memory; hence, the PFC may be voluntarily activated even during the "resting"
      condition that precedes task execution. The purpose of the present study was to
      investigate changes in voluntary pre-task activation as a result of aging using a
      paradigm that includes a longer intertrial interval (e.g., 30 sec) than has been
      used in previous studies. METHODS: A total of 120 cognitively normal adults
      (young: 60, old: 60) participated in this near-infrared spectroscopy (NIRS)
      study. All subjects performed 6 repetitions of the working memory task, which
      included a 30 sec resting period and a 28.8 sec task period. The resting period
      was divided into baseline and pre-task (preT) periods, and the task period was
      divided into early easy task (eT) and late difficult task (dT) periods. We then
      normalized the data, analyzed the magnitude of task-related NIRS responses in
      each period and compared the results between groups using an analysis of variance
      test. RESULTS: Statistical analyses revealed a significant interaction between
      group * optode location * period, in which hemodynamic responses in the PFC
      during the preT period were smaller in the elderly in than young adults. By
      contrast, during the task period, the hemodynamic responses were higher in the
      lateral PFC in the elderly than in young adults. Spearman's rank correlation
      analysis showed a positive correlation between hemodynamic changes during the
      preT period in the PFC and correct answer ratios in both groups. CONCLUSIONS:
      These findings suggest that more pre-task activation in the anterior PFC is
      related to better cognitive performance in humans. Thus, a reduction in this
      activation might partly explain cognitive decline in the elderly.

PMID- 24897307
TI  - Exposure-response modeling of clinical end points using latent variable indirect
      response models.
AB  - Exposure-response modeling facilitates effective dosing regimen selection in
      clinical drug development, where the end points are often disease scores and not
      physiological variables. Appropriate models need to be consistent with
      pharmacology and identifiable from the time courses of available data. This
      article describes a general framework of applying mechanism-based models to
      various types of clinical end points. Placebo and drug model parameterization,
      interpretation, and assessment are discussed with a focus on the indirect
      response models. 

PMID- 24897306
TI  - Inequalities in healthy life expectancy between ethnic groups in England and
      Wales in 2001.
AB  - OBJECTIVES: We aim to develop robust estimates of disability-free life expectancy
      (DFLE) and healthy life expectancy (HLE) for ethnic groups in England and Wales
      in 2001 and to examine observed variations across ethnic groups. DESIGN: DFLE and
      HLE by age and gender for five-year age groups were computed for 16 ethnic groups
      by combining the 2001 Census data on ethnicity, self-reported limiting long-term
      illness and self-rated health using mortality by ethnic group estimated by two
      methods: the Standardised Illness Ratio (SIR) method and the Geographically
      Weighted Method (GWM). RESULTS: The SIR and GWM methods differed somewhat in
      their estimates of life expectancy (LE) at birth but produced very similar
      estimates of DFLE and HLE by ethnic group. For the more conservative method
      (GWM), the range in DFLE at birth was 10.5 years for men and 11.9 years for
      women, double that in LE. DFLE at birth was highest for Chinese men (64.7 years,
      95% CI 64.0-65.3) and women (67.0 years, 95% CI 66.4-67.6). Over half of the
      ethnic minority groups (men: 10; women: 9) had significantly lower DFLE at birth
      than White British men (61.7 years, 95% CI 61.7-61.7) or women (64.1 years, 95%
      CI 64.1-64.2), mostly the Black, Asian and mixed ethnic groups. The lowest DFLE
      observed was for Bangladeshi men (54.3 years, 95% CI 53.7-54.8) and Pakistani
      women (55.1 years, 95% CI 54.8-55.4). Notable were Indian women whose LE was
      similar to White British women but who had 4.3 years less disability-free (95% CI
      4.0-4.6). CONCLUSIONS: Inequalities in DFLE between ethnic groups are large and
      exceed those in LE. Moreover, certain ethnic groups have a larger burden of
      disability that does not seem to be associated with shorter LE. With the
      increasing population of the non-White British community, it is essential to be
      able to identify the ethnic groups at higher risk of disability, in order to
      target appropriate interventions.

PMID- 24897309
TI  - Play fighting of juvenile golden hamsters (Mesocricetus auratus): effects of two
      types of social deprivation and days of testing.
AB  - The effects of social deprivation schedules and days of testing on the play
      fighting of juvenile golden hamsters were investigated. In Experiment 1, subjects
      totally (individually housed) or partially isolated (individually housed, but
      separated by a wire mesh 2 cm from another animal) for a period of 48 h spent
      significantly increased peer-peer bodily contact, play fighting, and play
      fighting relative time (% of bodily contact time spent in play fighting), but
      exhibited decreased locomotor activity on the 1st day of testing. In Experiment
      2, subjects reared since the 10th postnatal day with their mothers alone
      (chronically deprived of peer-peer social interactions) exhibited similar
      performances, except that locomotor activity was not affected. All dyads
      exhibited increased pinning turbulence (number of pinnings divided by time spent
      in play fighting) on the 1st day of testing, and the interactions between
      variables (deprivation schedules and days of testing) were statistically
      significant in most cases, suggesting that unfamiliarity between interactors also
      affect the performances of animals. We conclude that golden hamsters are
      sensitive to social deprivation, mothers do not substitute peer companions,
      animals reared in single-infant litters basically behave like socially-isolated
      animals, and the effects of induced social deprivation are reversible and
      disappear on days following testing. 

PMID- 24897308
TI  - Craniofacial anthropometry in newborns of Sikkimese origin.
AB  - BACKGROUND: Head and face dimensions vary according to race and geographical
      zone. Hereditary factors also greatly affect the size and shape of the head.
      There are important medical applications of craniofacial data specific to
      different racial and ethnic groups. METHODS: Various cranial and facial
      anthropometric parameters were assessed in singleton, healthy, full-term newborns
      of Sikkimese origin in a tertiary care hospital in Sikkim, India. The data were
      then analysed to determine statistically significant differences between sexes.
      RESULTS: Forty-five newborns were included in the study. Both male and female
      newborns were observed to be hyperbrachycephalic and hyperleptoprosopic. The only
      significant difference between the sexes was in commissural length, which was
      observed to be greater in male newborns. CONCLUSION: Craniofacial parameters in
      Sikkimese newborns vary in comparison with those of other newborns from around
      the world. Larger studies are needed in order to reveal sex-related variations.
      Similar studies on various racial groups in North-East India are needed to
      establish standards for populations with East Asian features.

PMID- 24897310
TI  - Serial feature negative training to a target unconditioned stimulus.
AB  - In serial feature-negative (SFN) training to a target unconditioned stimulus
      (US), eight rats received two types of intermingled trials: (1) trials in which a
      tone was followed by the delivery of a single food pellet US, and (2) trials in
      which the delivery of a single food pellet US was followed by three additional
      food pellets. Following SFN training, the tone showed little transfer to a
      partially reinforced light cue and the tone's negative modulation was eliminated
      after tone extinction. Implications for theories of occasion-setting are
      discussed. 

PMID- 24897311
TI  - Comparative study of emotional behaviour in three inbred strains of mice.
AB  - Anxious behaviour constitutes one of the markers that best differentiated the
      'non-emotional' C57BL/6 (C57) strain from the 'emotional' BALB/c (BALB) strain.
      Interestingly, C3H/He (C3H) mice, which possess a common genetic background to
      BALB, have also been found to be 'emotional' mice. The present study first
      illustrates that BALB and C3H mice exhibit a higher emotional level both in non
      constraining situation (free-exploratory paradigm) and in a stressful one
      (light/dark choice test). Second, the present results confirmed the hypothesis
      that trait anxiety, modelled neophobic reactions in the free-exploratory
      paradigm, is related to GABA-benzodiazepine system rather than to the
      serotoninergic one, in contrast to state anxiety, modelled by the light/dark
      choice test. Like in BALB mice, chlordiazepoxide was able to counteract the
      neophobic responses in C3H mice confronted with the free-exploratory paradigm, in
      contrast to 8-OH-DPAT which did not modify C3H behaviour in this test.
      Conversely, both chlordiazepoxide and 8-OH-DPAT reduced anxious reactions of BALB
      and C3H mice in the light/dark choice test, showing that BALB and C3H mice are
      sensitive to serotonin-interacting drugs only when confronted with a stressful
      situation. Furthermore, chlordiazepoxide and 8-OH-DPAT were found to be devoid of
      anxiolytic-like effect in C57 mice. The lack of anxiolytic-like activity of these
      compounds in C57 mice can be related to the low basal level of emotional
      reactions of this strain. Finally, the present results showed that chronic stress
      was able to blunt general emotional level of mice in both experimental situations
      and that both BALB and C3H mice were more sensitive to chronic stress than C57
      ones. In conclusion, BALB and C3H may be two strains of choice for testing
      potential anti-anxiety treatments which might be of great long-term benefit in
      the chronically anxious patients. Furthermore, these strains constitute
      interesting material for determining hereditary factors which presumably underlie
      the development of some chronic anxiety disorders. Finally, since C3H and BALB
      mice appeared particularly susceptible to chronic stress, it can be proposed that
      these strains may be a useful tool to examine the possible common origins of
      anxiety disorders and chronic stress-related disorders, such as certain forms of
      depression. 

PMID- 24897312
TI  - Extinction of the response to the female's urinary odour as a consequence of low
      dose X-irradiation in male hamster, occurs in conjunction with a marked
      suppression of aggressive behaviour.
AB  - In recent years concern over the biological effects of low-dose X-rays has been
      growing. I have noticed that fighting injuries usually observed among male Syrian
      hamsters tend to decrease in animals irradiated with low-dose X-rays. Therefore,
      quantitatively the effects of low-dose X-irradiation on aggressive behaviour were
      examined using a resident-intruder paradigm. Hamsters became gradually calm, and
      showed remarkably quiet behaviour 7-10 days following whole-body 5 or 15 cGy X
      irradiation. Only the anterior part of the head (olfactory system including
      orbits) exposure also induced the remarkable suppression of the aggressive
      behaviour. The calm behaviour induced by low-dose X-irradiation might be related
      to the changes in the olfactory function. In an additional experiment, the
      effects of low-dose X-irradiation on the olfactory system was examined using
      operant conditioning techniques, in which male hamsters were trained to
      discriminate between a conspecific female's urine and a water stimulus in return
      for a food reward. Following a 5 cGy dose of X-rays, the irradiated hamsters made
      slightly fewer correct discriminations relative to non-irradiated controls. A
      significant difference was found when the radiation dose was increased to 15 cGy.
      Similar results were obtained when the radiation exposure was restricted to the
      anterior portion of the head. Significant effects were not observed prior to the
      8th day post-exposure, and the effect was most pronounced 10 days after the
      exposure to X-rays. Possible relationships between the two effects are discussed.

PMID- 24897313
TI  - Sleep rhythmicity in infants: index of stress or maturation.
AB  - The rhythmicity of bouts of quiet sleep (QS) was assessed, starting immediately
      after the baby's birth. The subjects were 58 healthy fullterm, single-birth,
      newborn infants, 26 females and 32 males. Using a non-intrusive recording
      procedure, their sleep was monitored for 24-h periods on the 1st and 2nd
      postnatal days in the hospital, then for 2 days in the home at 6 months. The
      cyclicity index permitted determination of the degree of periodicity as well as
      whether the recurrence of QS bouts showed significant periodicity. The number of
      subjects with significant cyclicity increased from 34% of the group on postnatal
      day 1 to 73% at 6 months; cyclicity scores (CS) increased from 0.71 to 0.86; and
      mean cycle length increased from 51 to 57 min. Infants with significant cyclicity
      on day 1 had lower mental scores at 6 months; but infants with significant
      cyclicity at 6 months had higher mental scores at 1 year. In addition, the
      infants with significant cyclicity on day 1 had lower birth weights and were born
      to younger mothers; but these relationships were also reversed at 6 months.
      Finally, cyclicity scores at 6 months were significantly correlated with 1-year
      mental scores, but the function of this relationship was quadratic. Thus, while
      significant cyclicity was found from the first postnatal day, the results suggest
      that regularity in QS cycles in the newborn period has negative implications for
      development, while such regularity at 6 months has positive implications-although
      excessive rigidity in rhythms at the later age, in terms of extremely high
      cyclicity scores, was also an indicator of developmental compromise. 

PMID- 24897315
TI  - The acoustic behaviour of the bushcricket Tettigonia cantans I. Behavioural
      responses to sound and vibration.
AB  - The responses of Tettigonia cantans to species-specific song and substrate
      conducted vibration have been tested under three experimental regimes. When
      directional cues are adequate the sound source can be located by audition alone;
      where such cues fail to provide sufficient information then vibration signals
      become of value. In two-choice experiments vibrating substrates are preferred by
      both males and females moving towards the sound source. In multiple-choice
      experiments Tettigoniids may either detect and follow vibration gradients or the
      direction of the bending waves coming from the vibration source to orientate
      towards a conspecific. 

PMID- 24897314
TI  - Use of dens by radiotracked brown hares Lepus europaeus.

PMID- 24897316
TI  - The acoustic behaviour of the bushcricket Tettigonia cantans II. Transmission of
      airborne-sound and vibration signals in the biotope.
AB  - The airborne-sound and the vibratory signals produced by stridulating Tettigonia
      cantans males, and the transmission of these signals in the natural biotope were
      investigated. The song of T. cantans is composed of repeated uniform syllables
      with a rate of ca. 30/sec. Intensity approaches 100 dB SPL, 10 cm away from the
      animal. The spectrum shows three dominant frequency ranges around 8, 16 and 32
      kHz. Airborne transmission of the song in such vegetation layers as are found in
      the biotopes of T. cantans shows an excess attenuation which increases with
      frequency. The relative intensities of the frequency components of the song vary
      as a result of the kind of vegetation, the positions of emitter and receiver, and
      the separation distance. These relative differences in intensity may be useful
      during the phonotactic approach to conspecific partners, providing a measure of
      the distance from the sound source. Stridulating males also produce vibratory
      signals in the plants they sit on. The spectrum of these signals includes
      frequencies up to 8 kHz, the first dominant frequency of the song: low frequency
      components are induced in the plants via the legs and abdomen of the animal. The
      vibratory signals are transmitted mainly in the form of bending waves. Near the
      animal, amplitude modulation corresponds to that of the song. At greater
      distances, reflections and frequency-dependent propagation velocities, cause
      distortions of this time pattern. Transmission depends greatly on the mechanical
      properties of the particular plant, attenuation values of 20-50 dB/m being found.
      Nevertheless, in most cases, vibratory signals may be perceived up to 1.5 - 2
      metres away from a stridulating male. 

PMID- 24897317
TI  - Behavioural plasticity of lake charr (Salvelinus namaycush) x brook charr (S.
      fontinalis) F1 hybrids in response to varying social environment.
AB  - Lake x brook F1 hybrid charr were observed in heterogeneous groups with lake
      charr or brook charr to assess the effects of different species on hybrid social
      behaviour. Levels of behavioural plasticity were low in relation to the
      behavioural differences between the parental and hybrid types. Feeding behaviour
      showed the most dramatic change, with higher levels in the lake charr treatment
      and lower levels in the brook charr treatment than controls, suggesting social
      facilitation. Even though only two measures varied significantly between
      treatments, there was a tendency for the frequencies and durations of all
      agonistic measures to increase in the presence of lake charr and decrease with
      brook charr. A cost-benefit argument is presented to account for this trend. 

PMID- 24897318
TI  - Variability of response of the corn bunting, Emberiza calandra, to songs of
      different dialects.
AB  - Experiments on the corn bunting were carried out in two localities of different
      dialects. In the center of the territory of each bird, we played two natural
      songs: either one local song and one song of the foreign dialect or two local
      songs coming from a neighbor and from a non-neighboring individual. The following
      results were obtained: (1) The behavioral responses are always more intense to
      the local song than to the song of a foreign dialect. Thus, the behavior of the
      corn bunting is similar to that of species with dialects studied up to now. (2)
      Eighty percent of the birds tested with the song of the foreign dialect react
      weakly or not at all. This peculiarity, which is specific to the corn bunting,
      suggests limited possibilities of generalization in this species. (3) The
      behavioral responses to the songs of a neighbor and of a non-neighboring
      individual of the same locality, are aggressive and of the same intensity. This
      means that the song of a neighbor, emitted from a different place than usual, is
      perceived by the bird as a threat to its territory. 

PMID- 24897319
TI  - The systemic response of male mice to differential housing: A path-analytical
      approach.
AB  - Path analysis was used to examine the effects of grouping/individual housing,
      duration of differential housing (13 days or 10 weeks), and the age at which
      differential housing was initiated (at weaning or 4 months) on the physiology of
      male TT strain mice. Variables studied included body and relative ventral
      prostate, left testis and left adrenal gland weights, and plasma corticosterone
      level and (Na+) /(K+) ratio. Compared with grouped counterparts, individual
      housing produced lower adrenal weights and plasma corticosterone levels, but
      higher prostate weights. This housing condition also suppressed the plasma
      (Na+)/(K+) ratio, probably through an action on aldosterone secretion. The
      adrenal response to differential housing thus appears to be at a number of
      levels, involving at least two separate components. No evidence was found to
      support the notion that the gonadal response to grouping is mediated via the
      adrenal gland, although prolonged grouping does generate reduced testicular
      weights. 

PMID- 24897320
TI  - Sociality among captive hybrid macaques.
AB  - The social behavior of a group of twenty hybrid macaques and one M. fascicularis
      was investigated to determine the patterns of sociality and social integration
      within the group. Observation focused on the behavior categories of social
      affiliation and cohesion. Inter-animal proximity, social grooming, and inter
      animal contact were analyzed using a method of cliqual analysis. When compared to
      a group of M. nemestrina it was found that the hybrid females showed less
      proximity and contact and that the hybrid males received more noncontact
      aggression than their nemestrina counterparts. The results indicated that these
      hybrid macaques have formed an integrated social unit similar to that of a
      nonhybrid macaque group but without the female social nucleus. An hypothesis is
      put forward that groups of females put together may not form a social unit
      comparable to long term social groups. 

PMID- 24897321
TI  - The post-natal differentiation of sexual behaviour in the Japanese quail
      (Coturnix coturnix japonica).
AB  - An experiment was carried out to study the contribution of endogenous steroids
      during postnatal life to the sexual differentiation in Japanese quail. Male and
      female quail were gonadectomized at one week of age and when adult received
      testosterone silastic capsules. Seventy seven percent of these females showed
      male-type sexual behaviour and 46 percent even copulated. All males showed sexual
      behaviour including cloacal contact movements. Males and females grew cloacal
      glands of nearly identical sizes in response to the testosterone treatment. It is
      concluded that sexual differentiation in quail is at least in part a postnatal
      process and more research is needed to elucidate its exact mechanisms and time
      course. 

PMID- 24897322
TI  - Social play behaviours and insect predation in northern grasshopper mice
      (Onychomys leucogaster).
AB  - Play behaviours of northern grasshopper mice, Onychomys leucogaster , were
      observed from 27 to 61 days of age and after a brief period of social isolation.
      The mice were also observed during a simple test of cricket predation. With the
      exception of an active play-soliciting response, the play behaviours were quite
      similar to those described for other rodents. Play declined with increasing age
      and was strongly potentiated by social isolation. There was no discernable
      relationship between any of the play measures and efficiency of cricket
      predation. There were no detectable sex differences in either play or predation. 

PMID- 24897327
TI  - Stereotypies resulting from a deviation in the ontogenetic development of
      gerbils.
AB  - As a reaction to intensive housing conditions, Mongolian gerbils (Meriones
      unguiculatus) regularly develop stereotypic digging in early ontogeny. To
      determine how the development of stereotypic digging deviates from the
      development of digging in a natural setting, the development of digging in
      laboratory cages and an artifical burrow were compared. In the burrow treatment,
      young gerbils were raised inside the burrow and left it for the first time at a
      mean age of 21 days. They showed a strong tendency to retreat into the burrow and
      spent 91.6% of the time in it. Their digging consisted of short, non-stereotypic
      digging bouts. In contrast, digging of the young gerbils in the laboratory cages
      became increasingly longer and consisted of long-lasting, stereotypic digging
      bouts along with short, non-stereotypic bouts. This development deviated from the
      development in the burrow significantly from day 24. Stereotypic digging was
      interpreted as an intensification of digging due to a lack of retreating
      structures in the laboratory cages. Stereotypic digging was considered as an
      abnormal behavior because it failed to regulate retreating behavior. 

PMID- 24897328
TI  - Long-term retention of Pavlovian serial feature-positive and feature-negative
      discriminations.
AB  - Fifteen pigeons were concurrently trained with Pavlovian serial feature-positive
      (F-P) and feature-negative (F-N) discrimination tasks (A-, X->A+; B+, Y->B-), and
      retention of these discriminations was tested after a 2-week interval. The birds
      maintained the discriminations. After retraining of the original tasks, seven
      birds were tested with a one-month interval. Reliable deterioration was observed
      in the both discriminations due to increases in responding on the nonreinforced
      trials (A- for the F-P discrimination and Y->B- for the F-N discrimination). The
      remaining eight birds also were tested after a one-month interval, but they
      received 3-day retraining of the target stimuli (A- and B+) before the test.
      There was no loss of the discriminations in these birds, suggesting reactivation
      of discriminations by the target retraining. 

PMID- 24897329
TI  - Intraspecific identification and tolerance in the social-maternal behaviour of
      Coelotes terrestris (Araneae, Agelenidae).
AB  - In C. terrestris, we have shown that the reproductive state of the female exerts
      a major influence on its aptitude to tolerate the young and ensure maternal care.
      Thus, only pre-emergence females were found to be aggressive towards young
      homospecifics. The purpose of the present study is to show that female
      intolerance towards spiderlings during non-gregarious periods is not a
      manifestation of a predatory tendency. The experiments show: that C. terrestris
      females discriminate conspecific young from prey (i.e. cricket larvae) more of
      which they kill and ingest; that C. terrestris females also discriminate the
      young of their own species from alien ones; and that this discrimination is at
      least partially based on cuticular chemical stimuli during body contact. This
      information is relevant to the understanding of some aspects of social behaviour.

PMID- 24897330
TI  - Paw preferences in cats (Felis silvestris catus) living in a household
      environment.
AB  - Unrestrained, naive cats (Felis silvestris catus) (n=48: 28 males and 20
      females), living in a natural domestic environment, were studied for paw
      preferences using a food reaching test. A total of 46% were right-preferent, 44%
      were left-preferent and 10% were ambilateral. 60% of the cats in our sample used
      one paw 100% of the time. This preference was stable over time (10 weeks), and
      was not influenced by the presence of food residue on the cats' non-preferred
      paw. There was no difference between male and female cats in the proportions of
      left and right paw-preferent individuals. We have reviewed the literature
      reporting paw preferences in cats and conclude that in static food-reaching
      tests, domestic cats show a marked paw preference with an equal distribution of
      left- and right-preferent individuals. They do not, however, show a group or
      population bias toward the use of any one paw. There are no significant sex
      differences. In contrast, there is previously published evidence which appears to
      suggest that moving-target reaching tests uncover a left-sided behavioural
      asymmetry. 

PMID- 24897331
TI  - Habituation and memorization of spatial objects' configurations in mice from
      weaning to adulthood.
AB  - This experiment investigated the development of habituation and memorization
      capacities of C57BL/6 mice. After a first session on a classic open field, four
      groups of subjects (3, 4, 5 and 9 weeks of age) were exposed to objects arranged
      in a pre-defined spatial environment during three exploratory sessions.
      Subsequently, for the test session, half of the mice was exposed to the previous
      situation, while the other half was exposed to a novel situation with a different
      spatial configuration for testing animal's abilities to detect and react to a
      change in their environment. Analysis showed age-related differences in
      behavioural habituation patterns. Moreover, contrary to our expectancy based on
      previous studies, the youngest mice (3 week-old) didn't exhibit significant
      renewal of exploration of the displaced objects during the test session. This
      results indicated that the youngest mice react differently than the adult mice
      when they are confronted to a novel environment and especially seem enable to
      construct a long-lasting representation of their environment when this
      representation concerns proximal information. The results are discussed in
      relation to previous studies conducted on the radial maze and the Morris water
      maze and it seems that the abilities of the youngest mice to construct a
      representation of their environment are partially dependent upon the type of
      information available (i.e. proximal versus distal information). 

PMID- 24897332
TI  - An instance of viewpoint consistency in pigeon object recognition.
AB  - Pigeons were trained on a visual discrimination, a task using a TV monitor. Two
      different types of stimuli appeared as pictures on the TV screen, one was a
      feeder used in their home cages and the other a coffee mug. One group of the
      pigeons was trained to peck the screen when the feeder appeared on it, while the
      other group was trained to peck the screen when the mug appeared. The feeder was
      considered to be a 'familiar object' but the mug an 'unfamiliar object' for the
      subjects. After training, to peck the familiar object, the subjects showed
      generalization to unusual view pictures of the object, but they did not show such
      generalization after training to peck the unfamiliar object. These results
      suggest that view point consistency is limited to familiar objects in pigeons. 

PMID- 24897333
TI  - Working and scrounging by zebra finches in an operant task.
AB  - Groups of three zebra finches were housed in cages which could be adjoined to an
      operant chamber. Food was restricted and its availability was signalled by a red
      light projected behind an operant key (an autoshaping procedure). In addition to
      the shaping contingency, a single peck to the illuminated key, produced food
      immediately. Following the first peck to the illuminated key, by any subject in
      the group, the entire group was placed on a schedule of continuous reinforcement
      (CRF) wherein hopper operation was contingent upon a keypeck during the light.
      Comparison of individual's behavior revealed a differential pattern of operant
      working; one group member worked consistently, one worked periodically and one
      made few (if any) operant responses. All members consumed some reinforcers. The
      results suggest that zebra finches, under certain conditions, will form
      specialized labor roles. These data support similar demonstrations with primates
      (Chalmeau, R. and Galleau A., 1993. Behav. Processes, 28: 173-180), pigeons
      (Giraldeau, L. and Lefebvre L., 1987. Anim. Behav., 35: 387-394.) and rats
      (Thullier, F., Desor, D., Mos, J. and Krafft, B., 1992. Psychol. Behav., 53, 17
      20). 

PMID- 24897334
TI  - Ground-roosting in domestic fowl (Gallus gallus domesticus) in The Gambia: the
      anticipation of night.
AB  - The ground-roosting behaviour of a semi-feral population of domestic hens with
      broods of chicks was measured in The Gambia, West Africa. Although neither day
      length nor time of sunset changed significantly over the duration of the study
      (January-March 1995), mean daily light intensity showed a significant increase.
      This resulted in an increasingly rapid decline in light intensity at dusk as the
      season progressed. Hens went to roost significantly later in the day, and at
      lower light levels, over the course of the season. The results support a model
      suggesting that the cue to start roosting is a certain light level, constant over
      the season, but the 'settling period' required means that the hens finally roost
      at later times and at lower light levels as the season progresses. 

PMID- 24897335
TI  - Within-session patterns of responding with changes in the variability and
      probability of food delivery.
AB  - The present study was an attempt to determine the factors to which subjects
      sensitize and/or habituate within experimental sessions. Rats pressed a lever and
      pigeons pecked a key for food reinforcers delivered during a 60 min session. In
      experiment 1, subjects initially responded on a simple variable-interval 30 s
      schedule that consisted of 25 intervals. In subsequent conditions, the number of
      intervals in the series was decreased until subjects responded on a simple fixed
      interval 30 s schedule. In experiment 2, subjects always responded on a variable
      interval 15 s schedule that resulted in a stimulus change. The probability that a
      food reinforcer would accompany the stimulus change varied across conditions.
      Results showed that within-session patterns of responding did not change for
      either species with changes in the temporal pattern of reinforcer delivery
      (experiment 1). The within-session response patterns generally became flatter
      with decreases in the probability of food delivery for both species (experiment
      2). The present results indicate that subjects are sensitizing and/or habituating
      to the reinforcer itself and/or to some aspect of its delivery. They also help to
      highlight the strength of sensitization-habituation as an explanation for within
      session changes in responding. 

PMID- 24897336
TI  - Satellite tracking of a White Stork from Italy to Morocco.
AB  - Two young White Storks were tracked by satellite during a part of their first
      migratory journey from the nest colony (settled in Piedmont, NW Italy) to the
      wintering ground in Western Africa. Both birds left westward, but only one of the
      two birds provided reliable data which allowed the reconstruction of its
      migratory route along the coasts of France and Spain up to Morocco. A new aspect
      of the journey is that the bird did not pass from Europe to Africa at Gibraltar,
      the storks' known western route. Despite the storks' tendency to avoid flying
      over large stretches of sea, the tracked bird crossed the Alboran sea from De
      Gata Cape (Spain) to Tres Forcas Cape (Morocco), thus flying about 120 km over
      the open sea. 

PMID- 24897337
TI  - Effects of a brief sensorimotor training on the development of behavioral
      inhibition in the mouse.
AB  - In the young C57Bl6 mouse, the hyperexcitability phase ('pop-corn' stage) which
      normally occurs around the 16-18th postnatal day and lasts 3-6 days, was greatly
      shortened by an intensive sensorimotor training when the 'pop-corn' stage
      appeared. It was prevented when the animals were trained for 4 days before it
      appeared. This might suggest, at least in part, that an early short duration
      sensorimotor training increased the rate of maturation of the inhibitory systems
      that sustain the development of the motor behavior. 

PMID- 24897338
TI  - Categorisation of three-dimensional stimuli by humans and baboons: search for
      prototype effects.
AB  - A symbolic matching-to-sample procedure was adopted to investigate whether humans
      (n=2) and baboons (n=2) discriminate more accurately the prototypes of
      polymorphous categories than less typical exemplars. Subjects were initially
      trained to discriminate between two categories of stimuli defined by the
      possession of any two out of three possible binary features. In transfer,
      prototypes, which contained all the three feature values of their categories, and
      novel two-out-of-three feature exemplars were presented for discrimination.
      Humans solved the task in a propositional way, and showed no evidence for a
      better performance with the prototypes than with other exemplars. By contrast,
      monkeys classified the prototypes more accurately than the other exemplars. The
      analysis of training performance showed however, that their discriminations did
      not involve prototypical representations of the categories, but rather depended
      upon feature-and exemplar-response associations. It is argued that monkeys'
      better performance with the prototypes rested on peak shift and/or novelty
      effects. 

PMID- 24897339
TI  - Thermo-, pH-, and light-responsive poly(N-isopropylacrylamide-co-methacrylic
      acid)--Au hybrid microgels prepared by the in situ reduction method based on Au
      thiol chemistry.
AB  - In recent years, it has been an attractive challenge to fabricate multiple
      stimuli-responsive hybrid microgels composed of polymer microgel and gold
      nanoparticle (AuNP). Herein, we report on the detailed synthesis of poly(N
      isopropylacrylamide-co-methacrylic acid)--Au hybrid microgels by in situ
      reduction of gold precursor in the presence of thiol-functionalized poly(N
      isopropylacrylamide-co-methacrylic acid) microgels. The as-synthesized hybrid
      microgels showed well-defined swelling/deswelling transition in response to the
      surrounding temperature, pH, and light irradiation. The hybrid microgels had a
      unique microstructure where a large number of AuNP's distribute mainly in the
      interior of microgel with a fluff-like surface. The plasmonic property of the
      hybrid microgels can be modulated through the volume phase transition induced by
      the external triggers such as temperature and pH. In the reduction of 4
      nitrophenol catalyzed by the hybrid microgels, it was found that the reaction
      rate did not increase monotonously with temperature but greatly decreased in a
      certain temperature range, showing a tunable catalytic activity.

PMID- 24897340
TI  - A bryozoan species may offer novel antioxidants with anti-carbon-dioxide anion
      radical activity.
AB  - The antiradical activity of the freshwater bryozoan Hyalinella punctata water
      extracts (two samples, seasonal collection) was evaluated by using electron
      paramagnetic resonance spectroscopy against hydroxyl (?OH), superoxide anion
      (?O2(- )), methoxy (?CH2OH), carbon-dioxide anion (?CO2(- )), nitric-oxide (?NO)
      and 2,2-diphenyl-1-picrylhydrazyl (?DPPH) radicals. The extracts reduced the
      production of all tested radicals but to a varying degree. The better activity
      was observed against ?CO2(- ) and ?CH2OH radicals (54 +/- 5% and 44 +/- 4%, and
      58 +/- 6% and 22 +/- 2%, respectively) than towards ?DPPH, ?NO, ?OH and ?O2(- )
      radicals (59 +/- 6% and 1.0 +/- 0.1%, 46 +/- 5% and 14 +/- 1%, 7.0 +/- 0.5% and
      34 +/- 3%, and 33 +/- 3% and 0%, respectively). FTIR spectra of the both extracts
      indicate the presence of cyclic peptides and polypeptides which might be
      responsible for the observed activity. According to the experimental data
      obtained, H. punctata water extract may be considered as a novel promising
      resource of natural products with anti ?CO2(- ) radical activity. 

PMID- 24897341
TI  - Evidence of climate-induced range contractions in bull trout Salvelinus
      confluentus in a Rocky Mountain watershed, U.S.A.
AB  - Many freshwater fish species are considered vulnerable to stream temperature
      warming associated with climate change because they are ectothermic, yet there
      are surprisingly few studies documenting changes in distributions. Streams and
      rivers in the U.S. Rocky Mountains have been warming for several decades. At the
      same time these systems have been experiencing an increase in the severity and
      frequency of wildfires, which often results in habitat changes including
      increased water temperatures. We resampled 74 sites across a Rocky Mountain
      watershed 17 to 20 years after initial samples to determine whether there were
      trends in bull trout occurrence associated with temperature, wildfire, or other
      habitat variables. We found that site abandonment probabilities (0.36) were
      significantly higher than colonization probabilities (0.13), which indicated a
      reduction in the number of occupied sites. Site abandonment probabilities were
      greater at low elevations with warm temperatures. Other covariates, such as the
      presence of wildfire, nonnative brook trout, proximity to areas with many adults,
      and various stream habitat descriptors, were not associated with changes in
      probability of occupancy. Higher abandonment probabilities at low elevation for
      bull trout provide initial evidence validating the predictions made by
      bioclimatic models that bull trout populations will retreat to higher, cooler
      thermal refuges as water temperatures increase. The geographic breadth of these
      declines across the region is unknown but the approach of revisiting historical
      sites using an occupancy framework provides a useful template for additional
      assessments. 

PMID- 24897342
TI  - A meta-analysis of red yeast rice: an effective and relatively safe alternative
      approach for dyslipidemia.
AB  - OBJECTIVE: To explore whether red yeast rice is a safe and effective alternative
      approach for dyslipidemia. METHODS: Pubmed, the Cochrane Library, EBSCO host,
      Chinese VIP Information (VIP), China National Knowledge Infrastructure (CNKI),
      Wanfang Databases were searched for appropriate articles. Randomized trials of
      RYR (not including Xuezhikang and Zhibituo) and placebo as control in patients
      with dyslipidemia were considered. Two authors read all papers and independently
      extracted all relevant information. The primary outcomes were serum total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG),
      and high-density lipoprotein cholesterol (HDL-C). The secondary outcomes were
      increased levels of alanine transaminase, aspartate aminotransferase, creatine
      kinase, creatinine and fasting blood glucose. RESULTS: A total of 13 randomized,
      placebo-controlled trials containing 804 participants were analyzed. Red yeast
      rice exhibited significant lowering effects on serum TC [WMD = -0.97 (95% CI: 
      1.13, -0.80) mmol/L, P<0.001], TG [WMD = -0.23 (95% CI: -0.31, -0.14) mmol/L,
      P<0.001], and LDL-C [WMD = -0.87 (95% CI: -1.03, -0.71) mmol/L, P<0.001] but no
      significant increasing effect on HDL-C [WMD = 0.08 (95% CI: -0.02, 0.19) mmol/L,
      P = 0.11] compared with placebo. No serious side effects were reported in all
      trials. CONCLUSIONS: The meta-analysis suggests that red yeast rice is an
      effective and relatively safe approach for dyslipidemia. However, further long
      term, rigorously designed randomized controlled trials are still warranted before
      red yeast rice could be recommended to patients with dyslipidemia, especially as
      an alternative to statins.

PMID- 24897343
TI  - CloudDOE: a user-friendly tool for deploying Hadoop clouds and analyzing high
      throughput sequencing data with MapReduce.
AB  - BACKGROUND: Explosive growth of next-generation sequencing data has resulted in
      ultra-large-scale data sets and ensuing computational problems. Cloud computing
      provides an on-demand and scalable environment for large-scale data analysis.
      Using a MapReduce framework, data and workload can be distributed via a network
      to computers in the cloud to substantially reduce computational latency.
      Hadoop/MapReduce has been successfully adopted in bioinformatics for genome
      assembly, mapping reads to genomes, and finding single nucleotide polymorphisms.
      Major cloud providers offer Hadoop cloud services to their users. However, it
      remains technically challenging to deploy a Hadoop cloud for those who prefer to
      run MapReduce programs in a cluster without built-in Hadoop/MapReduce. RESULTS:
      We present CloudDOE, a platform-independent software package implemented in Java.
      CloudDOE encapsulates technical details behind a user-friendly graphical
      interface, thus liberating scientists from having to perform complicated
      operational procedures. Users are guided through the user interface to deploy a
      Hadoop cloud within in-house computing environments and to run applications
      specifically targeted for bioinformatics, including CloudBurst, CloudBrush, and
      CloudRS. One may also use CloudDOE on top of a public cloud. CloudDOE consists of
      three wizards, i.e., Deploy, Operate, and Extend wizards. Deploy wizard is
      designed to aid the system administrator to deploy a Hadoop cloud. It installs
      Java runtime environment version 1.6 and Hadoop version 0.20.203, and initiates
      the service automatically. Operate wizard allows the user to run a MapReduce
      application on the dashboard list. To extend the dashboard list, the
      administrator may install a new MapReduce application using Extend wizard.
      CONCLUSIONS: CloudDOE is a user-friendly tool for deploying a Hadoop cloud. Its
      smart wizards substantially reduce the complexity and costs of deployment,
      execution, enhancement, and management. Interested users may collaborate to
      improve the source code of CloudDOE to further incorporate more MapReduce
      bioinformatics tools into CloudDOE and support next-generation big data open
      source tools, e.g., Hadoop BigTop and Spark. AVAILABILITY: CloudDOE is
      distributed under Apache License 2.0 and is freely available at
      http://clouddoe.iis.sinica.edu.tw/.

PMID- 24897345
TI  - Molecular implications of drug-polymer solubility in understanding the
      destabilization of solid dispersions by milling.
AB  - The solubility of drugs in polymer matrixes has been recognized as one of the key
      factors governing the physical stability of solid dispersions. This study has
      explored the implications of drug solubility on the destabilization that occurs
      on milling, which is often used as an additional process for hot melt extruded
      (HME) solid dispersions. The theoretical drug solubility in the polymer was first
      predicted using various theoretical and experimental approaches. The
      destabilization effects of high-energy mechanical milling on the solid
      dispersions with drug loadings below and above the predicted solubility were then
      investigated using a range of thermal, microscopic, and spectroscopic techniques.
      Four model drug-polymer combinations were studied. The HME formulations with drug
      loading below the predicted solid solubility (undersaturated and true molecular
      dispersion) showed good stability against milling. In contrast, milling
      destabilized supersaturated HME dispersions via increasing molecular mobility and
      creating phase-separated, amorphous, drug-rich domains. However, these additional
      amorphous drug-rich domains created by milling show good stability under ambient
      conditions, though crystallization can be accelerated by additional heating.
      These results highlighted that the processing method used to prepare the solid
      dispersions may play a role in facilitating the stabilization of amorphous drug
      in supersaturated solid dispersions. The degree of supersaturation of the drug in
      the polymer showed significant impact on the destabilization behavior of milling
      on solid dispersions. An improved understanding of the destabilization behavior
      of solid dispersions upon milling can provide new insights into the processing
      related apparent solubility of drugs in polymers. 

PMID- 24897344
TI  - Protective role of glutathione peroxidase 4 in laser-induced choroidal
      neovascularization in mice.
AB  - PURPOSE: To evaluate the influence of glutathione peroxidase 4 (GPx4) expression
      in retinal pigment epithelium (RPE)/choroid tissue using a mouse model of laser
      induced choroidal neovascularization (CNV). METHODS: In this study, GPx4+/-,
      GPx4+/+, and GPx4-overexpressing transgenic mice were created for comparison. The
      mRNA and protein expression of vascular endothelial growth factor (VEGF)-A in
      RPE/choroid tissue were evaluated before and after CNV induction by laser.
      Moreover, we investigated the changes in the VEGF-A mRNA level in RPE/choroid
      tissue in the CNV model that have not been clearly shown previously. Lipid
      peroxidation in RPE/choroid tissue was evaluated by immunohistochemistry using
      antibody against 4-hydroxy-2-nonenal. To investigate the protective role of GPx4,
      the size of laser-induced CNV was compared on day 7 among the mice expressing
      different levels of GPx4. RESULTS: In the laser-induced CNV mouse model, laser
      treatment reduced the VEGF-A mRNA level in RPE/choroid tissue, while it increased
      the VEGF-A protein level. Evaluation of VEGF-A expression in RPE/choroid tissue
      of the GPx4+/-, GPx4+/+, and GPx4 transgenic mice revealed that GPx4 increased
      the VEGF-A protein level under physiological conditions (i.e., without laser
      treatment), while GPx4 suppressed the increase in the VEGF-A protein level under
      pathological conditions (i.e., after CNV induction by laser). In addition, GPx4
      reduced the CNV size in a dose-dependent manner in vivo. CONCLUSIONS: GPx4
      suppresses the increase in the VEGF-A protein level, which occurs during the
      development of pathological CNV, thus partly explaining the protective effect of
      GPx4 against CNV.

PMID- 24897347
TI  - Social preferences of domestic hens for domestic vs. red junglefowl males and
      females.
AB  - The striking dimorphism of male and female junglefowl may have evolved in large
      part due to female choice of mates. However, domestic fowl hens consistently
      chose domestic, not junglefowl, males as well as females in preference tests.
      Either genetic predisposition to favor junglefowl morphological features over
      those of the domestic types utilized in these tests was overridden by experience
      or such genetic predisposition does not exist in the breed we tested. 

PMID- 24897346
TI  - Pair comparison of durations.
AB  - Pigeons were trained on a pair comparison task where a red light of one duration
      was followed by a green light of a second duration. Following a duration pair two
      choice keys were lit and one choice was reinforced if the duration of red was
      longer than green, and the alternate choice was reinforced if green was longer
      than red. Duration pairs consisted of all possible combinations of the durations
      .5, 1, 2, and 4 sec in one condition, and 2, 4, 8, and 16 sec in a second
      condition. Generalization tests with novel duration pairs were given under both
      conditions. Under a final set of conditions, interstimulus intervals of 2, 5, 10,
      and 30 sec were interposed between the first (red) and second (green) durations.
      Pigeons responded appropriately in most cases, with accuracy a function of the
      relative temporal difference between the members of a duration pair. Accuracy on
      transfer problems was above 70% in most instances, but in some cases suggests
      factors apart from relative temporal differences influenced performance. Accuracy
      declined with increases in the interstimulus interval, but remained above chance
      levels even when the longest interstimulus interval was used. 

PMID- 24897348
TI  - Influence of resources on pig aggression and dominance.
AB  - Relationships between presence of feed and water and aggressive behaviour and
      correlations between dominance and use of these resources were investigated in 64
      five to eight week old pigs (Sus scrofa ). Pens of four randomly-selected pigs
      were established. Social dominance order was obtained largely within the first
      four hours but aggressive behaviour reached zero 19.4 hours after regrouping four
      pigs. Whether feed or water were present, pigs fought at similar levels. Pigs who
      were more aggressive did spend more time drinking water when resources were
      limited. Pigs that headed the aggressive dominance order did not gain preferred
      access to resources when they were in limited supply nor when they were abundant.

PMID- 24897349
TI  - Aggressive behaviour, sexual strategies and their relation to age in male Spanish
      ibex (Capra pyrenica ).
AB  - This study aimed to investigate the factors determining male reproductive success
      during the rutting season of the Spanish ibex. The rut lasts about seven weeks.
      At the begining of this period the old males engage in contests with each other,
      while the adult and subadult males spend more time courting the females. In the
      second half of this period, the old males court and gain reproductive acceptance
      while the adult and subadult males decrease their courtship activity. The old
      males also differ from the adult and subadults in the daily pattern of courtship
      activity. The old males test their relative strength and show agonistic displays
      as their most typical behaviour, while younger males tend towards more overt and
      primitive forms of fighting. Most contests involving males of all age classes
      occur between animals of similar age and these combats often end unresolved. The
      older of two combatants usually wins. Older males are preferred to younger ones
      by the females. The older the males, the more energy they expend in activities
      leading to mating and representing energy expenditure and the less time they use
      in those representing energy saving or recovery. 

PMID- 24897350
TI  - The effect of tied rank numbers on the linearity of dominance hierarchies.
AB  - The occurence of tied rank numbers in dominance hierarchies is discussed,
      especially its effect on the linearity of the hierarchy. This linearity is
      measured with Landau's index, that is calculated for several hierarchies with
      tied ranks on one, two of three levels. Linearity is mostly affected by ties in
      small groups with many ties. A distinction is made between a hierarchy of
      individuals and hierarchical levels. The phenomenon of despotism is called an
      extreme case of tied ranks. It is proposed to regard hierarchies with a linearity
      in a continuous scale. 

PMID- 24897351
TI  - Studies on the stridulation of Hylotrupes Bajulus (L.) (Cerambycidae,
      Coleoptera): Communication through support vibration - Morphology and mechanics
      of the signal.
AB  - The stridulation of Hylotrupes bajulus (L.) is examined with respect to ethology
      and functional morphology. The morphology outlines a defined species-specific
      structure. Biophysical aspects of sound emission are discussed. The sound pattern
      of stridulation is described. Its time structure is species-specific. Only the
      vibrational component of stridulation is an effective signal in the intraspecific
      communication of H. bajulus . It is a part of aggressive behaviour, where it
      constitutes menacing or impressing elememts. It is also found within the mating
      behaviour, where it forms a part of the tactile stimulation of the female by the
      male beetle. The 'open' organisation of the behaviour analysed is of interest.
      This open arrangement of the behaviour is somewhat surprising in view of the
      complex differentiation of the morphology. The specifity of the ethological
      structure is discussed. 

PMID- 24897352
TI  - The role of social experience in the development of sexual competence in Rattus
      norvegicus.
AB  - To clarify the hitherto ambiguous role of pubertal social experience in
      determining adult sexual competence in male Rattus norvegicus , the quality of
      the subjects' social interactions was manipulated. In Experiment 1, subjects were
      raised from weaning onwards in male-only groups, in groups with limited periods
      of social deprivation at various ages, or in total isolation. Only the latter
      showed a significant degree of sexual impairment. In Experiment 2, subjects were
      raised in mixed-sex groups, in total physical (but not visual or olfactory)
      isolation from a surrounding mixed-sex group, or in physical isolation except for
      one hour's social contact per day with a peer. All of these subjects were
      sexually competent as adults. It thus appears that, in the laboratory rat, social
      deprivation must consist of total physical and visual and/or olfactory isolation
      in order to produce a significant degree of sexual impairment. 

PMID- 24897353
TI  - Seasonal influences upon imprinting.

PMID- 24897359
TI  - Proceedings of the international congress on applied ethology in farm animals
      Kiel, 1984. Edited by J. Unshelm, G. Van Putten & K. Zeeb, 428pp.

PMID- 24897360
TI  - Avian archistriatal control of fear-motivated behavior and adrenocortical
      function.
AB  - Bilateral section of the efferent pathway (tractus occipitomesencephalicus) from
      the archistriatum of the duck depresses fear-motivated responses as measured by
      (a) latency to escape in a runway test; (b) latency to approach and drink in the
      experimenter's presence following water deprivation, and (c) number of agonistic
      responses directed to an object introduced into the home cage. Sectioning this
      pathway also raises plasma corticosteroid levels in both adult mallards and newly
      hatched chickens. Plasma corticosteroid levels were negatively correlated with
      latency to approach and drink in controls. Experimental reduction of the neutral
      output of the mallard archistriatum produces an animal that resembles the adult
      domesticated duck in its basal plasma corticosteroid level and in its avoidance
      behavior, suggesting that selection for reduced archistriatal activity occurs
      during domestication. 

PMID- 24897361
TI  - The effects of forebrain lesions on innate and imprinted colour, brightness and
      shape preferences in domestic chicks.
AB  - In previous reports we have found that lesions of the lateral forebrain of
      domestic chicks prevent or destroy imprinted preferential discrimination of
      objects differing in colour/ brightness and shape. However, there were non
      significant departures from random responding and it is possible that some
      residual learning was interacting with innate colour/ brightness preferences. An
      initial experiment in the present study showed that visually naive chicks had a
      significant blue and round shape preference when 1-2 days old. Visually
      experienced but non-imprinted chicks retained the round shape preference but
      showed weakened blue choice at 5-6 days of age. Chicks imprinted with a green
      slab showed a significant green preference at 5-6 days but chose slab and ball
      shapes equally. Taken together, these findings demonstrate imprinting for both
      colour and shape. Two further experiments tested lateral-, anterior-, and
      posterior-lesion and control chicks for retention of imprinted colour/brightness
      (mid-green) and shape (square) separately. Only the lateral- lesion group failed
      to choose the stimulus object with the familiar imprinted colour/brightness and
      instead chose the unfamiliar one (dark blue). No lesion group differed from the
      controls in the imprinted shape discriminations, all choosing the unfamiliar
      (round) as often as the familiar one. It appeared that the lateral-lesion chicks
      were like naive 1-day-olds in their colour/brightness preference but like
      imprinted birds in their shape preference. The final experiment tested the naive
      colour/brightness preferences of lateral- and anterior- lesion and control chicks
      using green and blue coloured discs in two tests with reversal of the brightness
      values. Both lesion groups behaved like controls in choosing dark blue in
      preference to light green. With reversed brightness values the controls showed a
      preference for the darker green discs, the anterior-lesion birds showed a slight
      tendency to choose the lighter blue disc, and the lateral-lesion birds reponded
      equally to the two colours. Thus, choices appeared to depend on brightness but in
      comparison with the controls there was some reduction in the brightness effect in
      the lateral-lesion birds and especially so in the anterior-lesion chicks. Since
      anterior lesions did not seriously impair the colour/brightness imprinted
      preference in the previous experiments, the reversal of the imprinted preference
      produced by lateral forebrain lesions is probably a true learning /memory loss
      and is not simply due to a colour or brightness sensory impairment. 

PMID- 24897362
TI  - [Not Available].
AB  - Adult male and female woodmice (Apodemus sylvaticus L.) were isolated for 4-6
      days in actographs. Time spent in the nest box, eating, drinking, locomotor
      activity in the enclosure ,and wheel-running were automatically recorded. The
      individual breeding cages were also equipped with a wheel. The immediate reaction
      following the introduction in an actograph, at about 11.00 a.m., lasted for 30
      120 min; locomotor activity and wheel-running was higher in the male than in the
      female group. During the first night, the mice were more active in the whole
      enclosure and ran less in the wheel than during the following nights. This was
      more evident in the female group, but both groups showed similar activity from
      the third day, and expressed more wheel-running than when in the breeding cage.
      When brought back into the breeding cage, the mice's wheel-running activity
      strongly decreased on the first night, and was even lower in the female group
      than before testing. In the actographs, increasing the accessible surface around
      the wheel led to a transitory drop in wheel-running for 1-2 days. Cleaning the
      breeding cage induced a similar but less pronounced change, On the whole, the
      novelty of a situation depressed wheel-running and increased locomotor activity
      for a few days. This reaction was more important in the female than in the male
      group, although the males showed a greater amount of activity as an immediate
      response to environmental changes. 

PMID- 24897363
TI  - Extinction of a newly acquired conditioned taste aversion: Effect of gustatory CS
      administered under anaesthesia.
AB  - Gustatory stimuli administered by intraperitoneal injection of concentrated
      flavour to anaesthetized rats cannot be associated with subsequent poisoning, but
      can extinguish an earlier established conditioned taste aversion (CTA). The
      differential sensitivity of CTA acquisition and extinction processes to
      anaesthesia was used to examine their interaction in the early stages of CTA
      learning. Male, hooded rats maintained on a 24-h water deprivation schedule were
      offered 15-min access to 0.1% saccharin (CS), were immediately afterwards
      anaesthetized with sodium pentobarbital and poisoned 30 min later by
      intraperitoneal injection of LiCl (US, 0.15 M, 2% body weight). Saccharin intake
      during a second presentation of the CS on the following day served as a measure
      of retention. Intraperitoneal injection of 2% saccharin (1% body weight) applied
      in the middle of the CS-US interval or 1 h after US administration did not
      decrease the CTA strength. Saccharin administered 2, 3, 4, and 5 h after US
      caused a gradually increasing CTA extinction which was almost complete with the 5
      h interval and slightly decreased with the 24-h delay. The failure of the
      saccharin injection applied 1 h after US to extinguish the newly acquired CTA is
      not due to coincidence of the gustatory stimulus with the continuing symptoms of
      poisoning, since LiCl administration preceding saccharin injection does not
      prevent CTA extinction in rats with well established CTA. It is concluded that
      the post-acquisition gradient of extinction reflects the decay of the short-term
      gustatory trace established during the initial saccharin drinking. 

PMID- 24897364
TI  - Time course and transition analysis of the behavioural effects of microinjection
      of pentobarbital and noradrenaline into the ventromedial hypothalamus of the rat.
AB  - Noradrenaline or the aspecific neural blocker pentobarbital were injected into
      the ventromedial hypothalamus (VMH) of male Wistar rats fed ad lib. Both drugs
      promptly induced eating behaviour which lasted for about 4-10 min. Feeding
      occurred equally well, either with food pellets scattered throughout the cage or
      when the pellets were concentrated in a small food cup. Compared with
      noradrenaline or with food deprivation, pentobarbital markedly depressed scanning
      for at least 12 min after injection, and decreased food-transport and undirected
      locomotion. When food pellets were scattered all over the floor, pentobarbital
      enhanced sniffing into the litter. This enhancement occurred just after the
      injection but before the break-through of feeding itself, and also after the fade
      out of feeding but before the recovery of scanning. As a rule, behaviour
      transitions leading to sniffing-litter were more preferred after pentobarbital
      than after either noradrenaline or food deprivation. Compared with pentobarbital
      and food deprivation, noradrenaline enhanced digging. With regard to the
      sequencing of behaviours, noradrenaline induced random chaining between
      behaviours, while pentobarbital yielded a most rigid chaining; food deprivation
      produced an intermediate result. The data are matched against expectations from
      Veening's funnel model of behaviour sequencing in VMH-blocked rats. The relation
      between the enhancement of sniffing-litter and of feeding after pentobarbital is
      discussed. 

PMID- 24897365
TI  - [Not Available].
AB  - The ontogenetic development of vocal communication was studied in 23 young red
      squirrels (Tamiasciurus hudsonicus) from four litters born in captivity. The age
      of appearance and sonogram analysis of the young's vocalizations are presented.
      In the newborn, discomfort and distress calls are the first vocalizations to
      appear. With the development of hearing, differentiation of distress and threat
      calls is noted and a contact call commences. Various alarm and threat calls occur
      when the young make their first appearance outside the nest. Territorial calls
      are heard for the first time around weaning. 

PMID- 24897366
TI  - Social play and rank order in rhesus monkeys (Macaca mulatta.
AB  - Social play is indispensable for adequate social development. Several authors
      have described a correlation between a mother's rank in the hierarchy and the
      rank of her infant. How the mother's rank is passed on to her infant was
      investigated. Social play in particular was studied. Social play among group
      members of rhesus monkeys (Macaca mulatta) was quantified in the laboratory. The
      group initially consisted of one adult male, six adult females and two infants.
      Four additional infants were born during the study period, all females. For each
      mother, social rank and order of giving birth was identical. There was a positive
      correlation between the social rank of the mother and the frequency of play. For
      the younger infants, this was not significantly due to age. Most play occured
      with the infant of the next (higher or lower) rank. The results suggest that both
      the amount of play and the partner's rank predispose the young monkey to assume
      its mother's rank. 

PMID- 24897372
TI  - WURCS: the Web3 unique representation of carbohydrate structures.
AB  - In recent years, the Semantic Web has become the focus of life science database
      development as a means to link life science data in an effective and efficient
      manner. In order for carbohydrate data to be applied to this new technology,
      there are two requirements for carbohydrate data representations: (1) a linear
      notation which can be used as a URI (Uniform Resource Identifier) if needed and
      (2) a unique notation such that any published glycan structure can be represented
      distinctively. This latter requirement includes the possible representation of
      nonstandard monosaccharide units as a part of the glycan structure, as well as
      compositions, repeating units, and ambiguous structures where linkages/linkage
      positions are unidentified. Therefore, we have developed the Web3 Unique
      Representation of Carbohydrate Structures (WURCS) as a new linear notation for
      representing carbohydrates for the Semantic Web. 

PMID- 24897370
TI  - Protein sub-nuclear localization prediction using SVM and Pfam domain
      information.
AB  - The nucleus is the largest and the highly organized organelle of eukaryotic
      cells. Within nucleus exist a number of pseudo-compartments, which are not
      separated by any membrane, yet each of them contains only a specific set of
      proteins. Understanding protein sub-nuclear localization can hence be an
      important step towards understanding biological functions of the nucleus. Here we
      have described a method, SubNucPred developed by us for predicting the sub
      nuclear localization of proteins. This method predicts protein localization for
      10 different sub-nuclear locations sequentially by combining presence or absence
      of unique Pfam domain and amino acid composition based SVM model. The prediction
      accuracy during leave-one-out cross-validation for centromeric proteins was
      85.05%, for chromosomal proteins 76.85%, for nuclear speckle proteins 81.27%, for
      nucleolar proteins 81.79%, for nuclear envelope proteins 79.37%, for nuclear
      matrix proteins 77.78%, for nucleoplasm proteins 76.98%, for nuclear pore complex
      proteins 88.89%, for PML body proteins 75.40% and for telomeric proteins it was
      83.33%. Comparison with other reported methods showed that SubNucPred performs
      better than existing methods. A web-server for predicting protein sub-nuclear
      localization named SubNucPred has been established at
      http://14.139.227.92/mkumar/subnucpred/. Standalone version of SubNucPred can
      also be downloaded from the web-server. 

PMID- 24897373
TI  - Genotype-phenotype correlations in a mountain population community with high
      prevalence of Wilson's disease: genetic and clinical homogeneity.
AB  - Wilson's disease is an autosomal recessive disorder caused by more than 500
      mutations in ATP7B gene presenting considerably clinical manifestations
      heterogeneity even in patients with a particular mutation. Previous findings
      suggested a potential role of additional genetic modifiers and environment
      factors on phenotypic expression among the affected patients. We conducted
      clinical and genetic investigations to perform genotype-phenotype correlation in
      two large families living in a socio-culturally isolated community with the
      highest prevalence of Wilson's disease ever reported of 1 ? 1130. Sequencing of
      ATP7B gene in seven affected individuals and 43 family members identified a
      common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and
      two asymptomatic patients and detected the presence of two out of seven
      identified single nucleotide polymorphisms in all affected patients. Symptomatic
      patients had similar clinical phenotype and age at onset (18 +/- 1 years) showing
      dysarthria and dysphagia as common clinical features at the time of diagnosis.
      Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of
      dystonia accompanied by unfavourable clinical outcomes. Our findings add value
      for understanding of genotype-phenotype correlations in Wilson's disease based on
      a multifamily study in an isolated population with high extent of genetic and
      environmental homogeneity as opposed to majority of reports. We observed an equal
      influence of presumed other genetic modifiers and environmental factors on
      clinical presentation and age at onset of Wilson's disease in patients with a
      particular genotype. These data provide valuable inferences that could be applied
      for predicting clinical management in asymptomatic patients in such communities.

PMID- 24897374
TI  - Tuberculosis management practices of private practitioners in Pune municipal
      corporation, India.
AB  - BACKGROUND: Private Practitioners (PP) are the primary source of health care for
      patients in India. Limited representative information is available on TB
      management practices of Indian PP or on the efficacy of India's Revised National
      Tuberculosis Control Programme (RNTCP) to improve the quality of TB management
      through training of PP. METHODS: We conducted a cross-sectional survey of a
      systematic random sample of PP in one urban area in Western India (Pune,
      Maharashtra). We presented sample clinical vignettes and determined the
      proportions of PPs who reported practices consistent with International Standards
      of TB Care (ISTC). We examined the association between RNTCP training and
      adherence to ISTC by calculating odds ratios and 95% confidence intervals.
      RESULTS: Of 3,391 PP practicing allopathic medicine, 249 were interviewed. Of
      these, 55% had been exposed to RNTCP. For new pulmonary TB patients, 63%
      (158/249) of provider responses were consistent with ISTC diagnostic practices,
      and 34% (84/249) of responses were consistent with ISTC treatment practices.
      However, 48% (120/249) PP also reported use of serological tests for TB
      diagnosis. In the new TB case vignette, 38% (94/249) PP reported use of at least
      one second line anti-TB drug in the treatment regimen. RNTCP training was not
      associated with diagnostic or treatment practices. CONCLUSION: In Pune, India,
      despite a decade of training activities by the RNTCP, high proportions of
      providers resorted to TB serology for diagnosis and second-line anti-TB drug use
      in new TB patients. Efforts to achieve universal access to quality TB management
      must account for the low quality of care by PP and the lack of demonstrated
      effect of current training efforts.

PMID- 24897376
TI  - Child road traffic crash injuries at the Red Cross War Memorial Children's
      Hospital in Cape Town, South Africa in 1992, 2002 and 2012.
AB  - Road traffic crashes are a significant cause of the disease burden among
      children, with the highest mortality in low- and middle-income countries. This
      observational study explores such injuries in Cape Town, South Africa through an
      analysis of data for cases in 1992, 2002 and 2012 at the Red Cross War Memorial
      Children's Hospital, a referral paediatric hospital for children younger than 13
      years. Descriptive and time trend analysis of demographic data as well as of the
      causes, severity and place of injury was conducted. Logistic regression and
      generalised linear models described factors influencing hospital admission. In
      the years 1992, 2002 and 2012, a total of 4690 patients presented with injuries
      sustained as a result of a road traffic crash. Nearly 50% (n = 2201) of them were
      between five and nine years of age, with 1.7 males for every female. Three
      quarters of those who got injured were pedestrians while the second most commonly
      injured ones were unrestrained passengers. The majority had minor injuries (58%),
      but with notably higher proportions with moderate to severe injuries in the years
      2002 and 2012. Forty per cent were admitted for inpatient treatment, with the
      highest proportion (50%) in 2002. Admission was related to mechanism and
      severity. The epidemiological factors assessed remain largely unchanged over the
      assessment points calling into question the impact of local safety strategies.

PMID- 24897378
TI  - Controlled localization of functionally active proteins to inclusion bodies using
      leucine zippers.
AB  - Inclusion bodies (IBs) are typically non-functional particles of aggregated
      proteins. However, some proteins in fusion with amyloid-like peptides, viral coat
      proteins, and cellulose binding domains (CBDs) generate IB particles retaining
      the original functions in cells. Here, we attempted to generate CBD IBs
      displaying functional leucine zipper proteins (LZs) as bait for localizing
      cytosolic proteins in E. coli. When a red fluorescent protein was tested as a
      target protein, microscopic observations showed that the IBs red-fluoresced
      strongly. When different LZ pairs with KDs of 8-1,000 uM were tested as the bait
      and prey, the localization of the red fluorescence appeared to change following
      the affinities between the LZs, as observed by fluorescence imaging and flow
      cytometry. This result proposed that LZ-tagged CBD IBs can be applied as an in
      vivo matrix to entrap cytosolic proteins in E. coli while maintaining their
      original activities. In addition, easy detection of localization to IBs provides
      a unique platform for the engineering and analyses of protein-protein
      interactions in E. coli. 

PMID- 24897375
TI  - Risk factors for recurrence, complications and mortality in Clostridium difficile
      infection: a systematic review.
AB  - BACKGROUND: Clostridium difficile infection (CDI) can lead to complications,
      recurrence, and death. Numerous studies have assessed risk factors for these
      unfavourable outcomes, but systematic reviews or meta-analyses published so far
      were limited in scope or in quality. METHODS: A systematic review was completed
      according to PRISMA guidelines. An electronic search in five databases was
      performed. Studies published until October 2013 were included if risk factors for
      at least one CDI outcome were assessed with multivariate analyses. RESULTS: 68
      studies were included: 24 assessed risk factors for recurrence, 18 for
      complicated CDI, 8 for treatment failure, and 30 for mortality. Most studies
      accounted for mortality in the definition of complicated CDI. Important variables
      were inconsistently reported, such as previous episodes and use of antibiotics.
      Substantial heterogeneity and methodological limitations were noted, mainly in
      the sample size, the definition of the outcomes and periods of follow-up,
      precluding a meta-analysis. Older age, use of antibiotics after diagnosis, use of
      proton pump inhibitors, and strain type were the most frequent risk factors for
      recurrence. Older age, leucocytosis, renal failure and co-morbidities were
      frequent risk factors for complicated CDI. When considered alone, mortality was
      associated with age, co-morbidities, hypo-albuminemia, leucocytosis, acute renal
      failure, and infection with ribotype 027. CONCLUSION: Laboratory parameters
      currently used in European and American guidelines to define patients at risk of
      a complicated CDI are adequate. Strategies for the management of CDI should be
      tailored according to the age of the patient, biological markers of severity, and
      underlying co-morbidities.

PMID- 24897380
TI  - Recovery of permittivity and depth from near-field data as a step toward infrared
      nanotomography.
AB  - The increasing complexity of composite materials structured on the nanometer
      scale requires highly sensitive analytical tools for nanoscale chemical
      identification, ideally in three dimensions. While infrared near-field microscopy
      provides high chemical sensitivity and nanoscopic spatial resolution in two
      dimensions, the quantitative extraction of material properties of three
      dimensionally structured samples has not been achieved yet. Here we introduce a
      method to perform rapid recovery of the thickness and permittivity of simple 3D
      structures (such as thin films and nanostructures) from near-field measurements,
      and provide its first experimental demonstration. This is accomplished via a
      novel nonlinear invertible model of the imaging process, taking advantage of the
      near-field data recorded at multiple harmonics of the oscillation frequency of
      the near-field probe. Our work enables quantitative nanoscale-resolved optical
      studies of thin films, coatings, and functionalization layers, as well as the
      structural analysis of multiphase materials, among others. It represents a major
      step toward the further goal of near-field nanotomography. 

PMID- 24897379
TI  - Fra2 is a co-regulator of Fep1 inhibition in response to iron starvation.
AB  - Iron is required for several metabolic functions involved in cellular growth.
      Although several players involved in iron transport have been identified, the
      mechanisms by which iron-responsive transcription factors are controlled are
      still poorly understood. In Schizosaccharomyces pombe, the Fep1 transcription
      factor represses genes involved in iron acquisition in response to high levels of
      iron. In contrast, when iron levels are low, Fep1 becomes inactive and loses its
      ability to associate with chromatin. Although the molecular basis by which Fep1
      is inactivated under iron starvation remains unknown, this process requires the
      monothiol glutaredoxin Grx4. Here, we demonstrate that Fra2 plays a role in the
      negative regulation of Fep1 activity. Disruption of fra2+ (fra2Delta) led to a
      constitutive repression of the fio1+ gene transcription. Fep1 was consistently
      active and constitutively bound to its target gene promoters in cells lacking
      fra2+. A constitutive activation of Fep1 was also observed in a php4Delta
      fra2Delta double mutant strain in which the behavior of Fep1 is freed of its
      transcriptional regulation by Php4. Microscopic analyses of cells expressing a
      functional Fra2-Myc13 protein revealed that Fra2 localized throughout the cells
      with a significant proportion of Fra2 being observed within the nuclei. Further
      analysis by coimmunoprecipitation showed that Fra2, Fep1 and Grx4 are associated
      in a heteroprotein complex. Bimolecular fluorescence complementation experiments
      brought further evidence that an interaction between Fep1 and Fra2 occurs in the
      nucleus. Taken together, results reported here revealed that Fra2 plays a role in
      the Grx4-mediated pathway that inactivates Fep1 in response to iron deficiency. 

PMID- 24897382
TI  - Oral anticoagulation in patients with cancer who have no therapeutic or
      prophylactic indication for anticoagulation.
AB  - BACKGROUND: Several basic research and clinical studies have led to the
      hypothesis that oral anticoagulants may improve the survival of patients with
      cancer through an antitumor effect in addition to their antithrombotic effect.
      OBJECTIVES: To evaluate the efficacy and safety of oral anticoagulants in
      patients with cancer with no therapeutic or prophylactic indication for
      anticoagulation. SEARCH METHODS: We performed a comprehensive search for studies
      of anticoagulation in patients with cancer including 1. a February 2013
      electronic search of the following databases: Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, and EMBASE; 2. a handsearch of the American
      Society of Clinical Oncology (starting with its first volume, 1982) and of the
      American Society of Hematology (starting with the 2003 issue); 3. checking of
      references of included studies; 4. use of the 'related citation' feature in
      PubMed; and 5. searching clinical trials.gov for ongoing studies. SELECTION
      CRITERIA: Randomized controlled trials (RCTs) comparing vitamin K antagonist or
      other oral anticoagulants with no intervention or placebo in patients with cancer
      without clinical evidence of venous thromboembolism. DATA COLLECTION AND
      ANALYSIS: Using a standardized data form, we extracted data on risk of bias,
      participants, interventions and outcomes of interest that included all-cause
      mortality, venous thromboembolism, major bleeding, and minor bleeding. MAIN
      RESULTS: Of 9559 identified citations, seven RCTs (eight reports) fulfilled the
      inclusion criteria. The oral anticoagulant was warfarin in six of these RCTs and
      apixaban in the seventh RCT. The comparator was either placebo or no
      intervention. The use of warfarin had no effect on mortality at six months (risk
      ratio (RR) 0.98; 95% confidence interval (CI) 0.82 to 1.22), one year (RR 0.97;
      95% CI 0.89 to 1.04), two years (RR 0.98; 95% CI 0.81 to 1.18), or five years (RR
      0.92; 95% CI 0.83 to 1.01). One study assessed the effect of warfarin on venous
      thromboembolism and did not show or exclude a beneficial or detrimental of effect
      (RR 0.15; 95% CI 0.02 to 1.20). Warfarin increased both major bleeding (RR 4.24;
      95% CI 1.86 to 9.65) and minor bleeding (RR 3.19; 95% CI 1.83 to 5.55). We judged
      the quality of evidence as moderate for all outcomes.The study assessing the
      effect of apixaban did not show or exclude a beneficial effect or detrimental of
      apixaban on mortality at six months (RR 0.16; 95% CI 0.01 to 1.66); major
      bleeding (RR 0.62; 95% CI 0.06 to 6.63); and minor bleeding (RR 2.87; 95% CI 0.16
      to 51.82). We judged the quality of evidence as low for all outcomes. AUTHORS'
      CONCLUSIONS: Existing evidence does not suggest a mortality benefit from oral
      anticoagulation in patients with cancer while the risk for bleeding is increased.

PMID- 24897383
TI  - An outbreak of Streptococcus pyogenes surgical site infections in a
      cardiovascular surgery department.
AB  - BACKGROUND: We report an outbreak of surgical site infections due to genetically
      related strains of Streptococcus pyogenes in a cardiovascular surgery department.
      METHODS: The practices that were possibly related to the outbreak were
      investigated through direct observation and interviews with staff by an infection
      control team. Surveillance sampling from patients, health-care workers, and
      environment were done for the investigation of the source. Pulsed-field gel
      electrophoresis was used to investigate a clonal relationship among the S.
      pyogenes isolates. RESULTS: Four patients operated on in the cardiovascular
      surgery department developed surgical site infection due to S. pyogenes.
      Molecular characterization of S. pyogenes done by pulsed-field gel
      electrophoresis revealed the same strain. CONCLUSIONS: Although a definite source
      for the outbreak could not be identified, probably lack of adherence to hand
      hygiene practices during surgical dressings, contamination, and cross
      contamination led to this outbreak.

PMID- 24897381
TI  - Dexamethasone-induced autophagy mediates muscle atrophy through mitochondrial
      clearance.
AB  - Glucocorticoids, such as dexamethasone, enhance protein breakdown via ubiquitin
      proteasome system. However, the role of autophagy in organelle and protein
      turnover in the glucocorticoid-dependent atrophy program remains unknown. Here,
      we show that dexamethasone stimulates an early activation of autophagy in L6
      myotubes depending on protein kinase, AMPK, and glucocorticoid receptor activity.
      Dexamethasone increases expression of several autophagy genes, including ATG5,
      LC3, BECN1, and SQSTM1 and triggers AMPK-dependent mitochondrial fragmentation
      associated with increased DNM1L protein levels. This process is required for
      mitophagy induced by dexamethasone. Inhibition of mitochondrial fragmentation by
      Mdivi-1 results in disrupted dexamethasone-induced autophagy/mitophagy.
      Furthermore, Mdivi-1 increases the expression of genes associated with the
      atrophy program, suggesting that mitophagy may serve as part of the quality
      control process in dexamethasone-treated L6 myotubes. Collectively, these data
      suggest a novel role for dexamethasone-induced autophagy/mitophagy in the
      regulation of the muscle atrophy program. 

PMID- 24897384
TI  - First total syntheses and antimicrobial evaluation of penicimonoterpene, a marine
      derived monoterpenoid, and its various derivatives.
AB  - The first total synthesis of marine-derived penicimonoterpene (+/-)-1 has been
      achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction
      as the key step to construct the basic carbon skeleton. A total of 24 new
      derivatives of 1 have also been designed and synthesized. Their structures were
      characterized by analysis of their 1H NMR, 13C NMR and HRESIMS data. Some of them
      showed significant antibacterial activity against Aeromonas hydrophila,
      Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum,
      V. harveyi and/or V. parahaemolyticus, and some showed activity against plant
      pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or
      Fusarium graminearum). Some of the derivatives exhibited antimicrobial MIC values
      ranging from 0.25 to 4 MUg/mL, which were stronger than those of the positive
      control. Notably, Compounds 3b and 10 showed extremely high selectively against
      plant-pathogenic fungus F. graminearum (MIC 0.25 MUg/mL) and pathogenic bacteria
      E. coli (MIC 1 MUg/mL), implying their potential as antimicrobial agents. SAR
      analysis of 1 and its derivatives indicated that modification of the carbon
      carbon double bond at C-6/7, of groups on the allylic methylene unit and of the
      carbonyl group at C-1, effectively enhanced the antimicrobial activity. 

PMID- 24897385
TI  - Numerosol A-D, new cembranoid diterpenes from the soft coral Sinularia numerosa.
AB  - Four new cembrane-type diterpenes; numerosol A-D (1-4); along with a known
      steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral
      Sinularia numerosa. The structures of these metabolites were determined by
      extensive analysis of spectroscopic data. Gibberoketosterol (5) exhibited
      cytotoxicity against P-388 (mouse lymphocytic leukemia) cell line with an ED50 of
      6.9 MUM. 

PMID- 24897387
TI  - PARP inhibitor activates the intrinsic pathway of apoptosis in primary lung
      cancer cells.
AB  - This investigation was aimed to see whether PJ34(TM), a PARP inhibitor, could
      exert cytotoxicity in six nonsmall cell lung cancer cell lines developed from
      surgically resected tissues. Using various biochemical assays, we have seen that
      PJ34(TM) effects are consistent between untreated and treated samples but still
      somewhat variable between each cell line. Changes in protein expression and
      mitochondrial membrane potential between treated and untreated cells were
      indicating the possibility of apoptosis induction through an intrinsic pathway
      which causes cytotoxicity. Present results open the possibility of elucidating a
      decisive mechanism and effectiveness of chemotherapeutics specific to a patient.

PMID- 24897388
TI  - Expression and proliferation-promoting role of lymphoid enhancer-binding factor 1
      in human clear cell renal carcinoma.
AB  - Lymphoid enhancer-binding factor 1 (LEF1) has been regarded as an important gene
      for carcinogenesis in many malignancies, however, the role of LEF1 in the
      progression of human renal cell carcinoma (RCC) has not been well studied. In
      this study, we investigated the expression of LEF1 in human RCC and the effect on
      proliferative ability of RCC cells. RCC samples from 138 patients who underwent
      radical nephrectomy were used in this study, the expression of LEF1 protein was
      determined by immunohistochemistry and Western blot, mRNA expression was analyzed
      by RT-PCR and real-time PCR. To investigate the effect of LEF1 on the
      proliferation of RCC cells, a LEF1 vector was transfected into RCC cells and LEF1
      expression was also decreased by using siRNA. Proliferative ability of RCC cells
      was examined by WST-1 assay and a xenograft study with BALB/C nude mice. Our
      results indicated that LEF1 expression was significantly increased in stage III,
      IV and grade 3 RCC than in normal kidney, however, decreased LEF1 expression was
      found in low-stage and grade RCC compared to that in normal kidney, the
      expression of LEF1 was correlated to tumor stages, histologic grade, and tumor
      sizes in RCC. The effect of LEF1 on the proliferation in RCC was also analyzed,
      our results suggested that RCC cells expressing high levels of LEF1 had
      significantly increased proliferative ability compared to control cell lines, in
      contrast, RCC cells with a low LEF1 expression had lower proliferative ability.
      Moreover, LEF1 promoted proliferation of RCC cells depending on suppressing G2/M
      cell-cycle arrest. Our study demonstrated that the expression of LEF1 is
      associated with the progression of RCC and that LEF1 maybe involved in the
      development of RCC, these suggested LEF1 play a key role and might serve as a
      therapeutic target in treating advanced RCC.

PMID- 24897389
TI  - Downregulation of CIC does not associate with overexpression of ETV1 or MAP
      kinase pathway activation in gastrointestinal stromal tumors.
AB  - ETV1 is a key factor in gastrointestinal stromal tumors (GIST), and is promoted
      by CIC downregulation in melanoma. We investigated CIC, ETV1, and the MAPK
      pathway in GIST. Downregulation of CIC protein levels as assessed by
      immunostaining was seen in 17/144 GIST, but was not associated with ETV1 or
      pMEK1/2 expression, KIT and PDGFRA mutations, copy number variations (CNV) of
      19q13, and clinical factors. However, the data indicate that the incidence of CIC
      downregulation may differ for GISTs in different locations in the
      gastrointestinal tract, and that CNV of 19q13 is associated with shorter disease
      free survival.

PMID- 24897390
TI  - Need for CT-based bone density modelling in finite element analysis of a shoulder
      arthroplasty revealed through a novel method for result analysis.
AB  - Treatment of common pathologies of the shoulder complex, such as rheumatoid
      arthritis and osteoporosis, is usually performed by total shoulder arthroplasty
      (TSA). Survival of the glenoid component is still a problem in TSA, whereas the
      humeral component is rarely subject to failure. To set up a finite element
      analysis (FEA) for simulation of a TSA in order to gain insight into the
      mechanical behaviour of a glenoid implant, the modelling procedure and the
      application of boundary conditions are of major importance because the computed
      result strongly depends upon the accuracy and sense of realism of the model. The
      goal of this study was to show the influence on glenoid stress distribution of a
      patient-specific bone density distribution compared with a homogenous bone
      density distribution for the purpose of generating a valid model in future FEA
      studies of the shoulder complex. Detailed information on the integration of bone
      density properties using existing numerical models as well as the applied
      boundary conditions is provided. A novel approach involving statistical analysis
      of values derived from an FEA is demonstrated using a cumulative distribution
      function. The results show well the mechanically superior behaviour of a
      realistic bone density distribution and therefore emphasise the necessity for
      patient-specific simulations in biomechanical and medical simulations.

PMID- 24897391
TI  - Postnatal kidney maturation regulates renal artery myogenic constriction.
AB  - AIM: Intravascular pressure-induced vasoconstriction (myogenic constriction) is
      central to renal blood flow autoregulation. At term, kidney maturation is
      functionally incomplete. Premature neonates are at risk of kidney dysfunction.
      However, it is unclear whether renal artery myogenic constriction is altered
      after preterm birth. Here, we compared renal artery myogenic constriction in full
      term and preterm pigs during the first week of life. METHODS: We investigated
      myogenic constriction in small interlobular arteries isolated from the kidneys of
      pigs delivered at term and at 91% of term (with and without 96 h of neonatal
      intensive care). RESULTS: Cross-sectional area, media/lumen ratio, and luminal
      diameter measured under passive conditions were similar in arteries from full
      term and preterm pig kidneys. An acute elevation in intravascular pressure from
      20 to 100 mm Hg increased arterial wall tension and induced steady-state
      constriction of the arteries. However, arteries isolated from newly born preterm
      pigs (within 24 h) developed greater myogenic tone and lower active wall tension
      compared with arteries from full-term and 4-day-old preterm neonates. Pressure
      induced elevation in intracellular Ca2+ was also larger in arteries from newly
      born preterm pigs compared with full-term and 4-day-old preterm pigs. CONCLUSION:
      Myogenic constriction is elevated in newly born preterm pigs. Our data also
      suggests that postnatal kidney maturation may modulate renal blood flow
      autoregulation.

PMID- 24897392
TI  - Variations of blood cells in prediction of gestational diabetes mellitus.
AB  - OBJECTIVE: This study aims to evaluate the value of increasing inflammation in
      predicting gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Subjects
      in this cross-sectional study included 302 GDM and 310 normal pregnancies before
      20 weeks. Sociodemographic and pregnancy characteristics as well as blood
      parameters were acquired by maternal health booklet, medical records and
      laboratory information systems. Blood cell parameters were compared between the
      two groups by independent sample t-tests. Multivariate logistic regression, chi2
      test, receiver operator characteristic curve (ROC), and Fisher's linear
      discriminant were performed to analyze the screening effects of variables in
      developing GDM. RESULTS: Women with GDM had significantly higher neutrophil
      (NEU), lymphocyte (LYM), platelet (PLT) and erythrocyte (RBC) counts, and were
      positively correlated with GDM. NEU (odds ratios, OR, 1.22) and LYM (OR, 2.01)
      were independently associated with the development of GDM (P<0.001). The OR of
      the mean platelet volume (MPV) and mean cell volume (MCV) were 0.84 and 0.92,
      respectively (P<0.01 for both). The efficiency of Fisher's equations in correctly
      classifying cases of GDM from 4 to 20 weeks of gestation was 70.06%. CONCLUSIONS:
      Maternal WBC, RBC, and PLT counts are important correlates of GDM. Increased
      volume of RBC and PLT might protect pregnant women from development of GDM.

PMID- 24897393
TI  - A cerclage is not a modified total cervical occlusion!

PMID- 24897394
TI  - The effect of the use of oxytocin on blood loss during different postpartum
      periods.
AB  - OBJECTIVE: Postpartum hemorrhage is the most important reason for maternal
      mortality. In developed countries, the reason of 13% of maternal deaths is
      postpartum hemorrhage while this percentage reaches more than 30% in other
      countries. In this study, the effect of oxytocin use in different times at the
      3rd stage of delivery on changes in the postpartum hemoglobin levels was
      compared. DESIGN AND SETTING: In the study, 89 pregnant women to whom oxytocin
      was administered after placenta separation were studied in Group 1, 89 pregnant
      women were included in Group 2, and oxytocin was administered after delivery of
      the shoulder. The levels of hemoglobin and hematocrit before and after delivery
      were quantified. RESULTS: The biochemical parameters were examined, there was no
      significant statistical differences in the levels of hemoglobin and hemotocrit
      before delivery between the two groups. When compared to Group 1, Delta
      hemoglobin (P=>0.001), Delta-hematocrit (P=>0.001), the change between the
      prepartum and postpartum hemoglobin percentage (P<=0.001), and change between the
      prepartum and postpartum hemotocrit percentage (P<=0.001) were statistically
      lower in Group 2. CONCLUSIONS: It was determined that the use of oxytocin after
      shoulder delivery has more effects on decreasing the amount of postpartum
      hemorrhage.

PMID- 24897396
TI  - The relaxant actions of ethanolic extract of Tridax procumbens (Linn.) on rat
      corpus cavernosum smooth muscle contraction.
AB  - BACKGROUND: The effect of Tridax procumbens aqueous ethanolic extract on the rat
      corpus cavernosum smooth muscles was evaluated in the present study. METHOD:
      Corpus cavernosum strips obtained from healthy, young, adult male Wistar albino
      rats (250-300 g) were precontracted with phenylephrine (10-7 M) or KCl (60 mM)
      and then treated with various concentrations of T. procumbens extract (0.15-1.05
      mg/mL). The change in corpus cavernosum strip tension was recorded. The
      interactions between T. procumbens extract with acetylcholine and with sodium
      nitroprusside were also evaluated. RESULTS: The results indicated that corpus
      cavernosum strips relaxation induced by T. procumbens extract was concentration
      dependent and this was significant (p<0.5). Pre-treatment with a nitric oxide
      synthase (NOS) inhibitor (N(1) nitro-L-arginine-methyl ester, l-NAME), did not
      completely inhibit the relaxation. However, T. procumbens extract (0.6 mg/mL)
      significantly (p<0.5) enhanced both acetylcholine- and sodium nitroprusside
      induced corpus cavernosum strips relaxation. CONCLUSIONS: RESULTS suggest that T.
      procumbens extract has a concentration-dependent relaxant effect on the isolated
      rat corpus cavernosum. The mechanism of action of T. procumbens extract is
      complex. A part of its relaxing effect is mediated directly by the release of NO
      from endothelium which may improve erectile dysfunction.

PMID- 24897397
TI  - Harmonization in hemolysis detection and prevention. A working group of the
      Catalonian Health Institute (ICS) experience.
AB  - BACKGROUND: Hemolysis is the main cause of non-quality samples in clinical
      laboratories, producing the highest percentage of rejections in the external
      assurance programs of preanalytical quality. The objective was to: 1) study the
      agreement between the detection methods and quantification of hemolysis; 2)
      establish comparable hemolysis interference limits for a series of tests and
      analytical methods; and 3) study the preanalytical variables which most influence
      hemolysis production. METHODS: Different hemoglobin concentration standards were
      prepared using the reference method. Agreement was studied between automated
      methods [hemolytic indexes (HI)] and reference method, as well as the
      interference according to hemolysis degree in various biochemical tests was
      measured. Preanalytical variables which could influence hemolysis production were
      studied: type of extraction, type of tubes, transport time, temperature and
      centrifugation conditions. RESULTS: Good agreement was obtained between
      hemoglobin concentrations measured using the reference method and HI, for the
      most of studied analyzers, particularly those giving quantitative HI. The
      hemolysis interference cut-off points obtained for the majority of tests studied
      (except LDH, K) are dependent on the method/analyzer utilized. Furthermore,
      discrepancies have been observed between interference limits recommended by the
      manufacturer. The preanalytical variables which produce a lower percentage of
      hemolysis rejections were: centrifugation at the extraction site, the use of
      lower volume tubes and a transport time under 15 min at room temperature.
      CONCLUSIONS: The setting of interference limits (cut-off) for each used
      test/method, and the study of preanalytical variability will assist to the
      results harmonization for this quality indicator.

PMID- 24897395
TI  - Are preterm newborns who have relative hyperthyrotropinemia at increased risk of
      brain damage?
AB  - BACKGROUND: We sought to disentangle the contributions of hyperthyrotropinemia
      (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained
      systemic inflammation (ISSI) to structural and functional indicators of brain
      damage. METHODS: We measured the concentrations of thyroid-stimulating hormone
      (TSH) on day 14 and of 25 inflammation-related proteins in blood collected during
      the first 2 postnatal weeks from 786 infants born before the 28th week of
      gestation who were not considered to have hypothyroidism. We defined
      hyperthyrotropinemia (HTT) as a TSH concentration in the highest quartile for
      gestational age on postnatal day 14 and ISSI was defined as a concentration in
      the top quartile for gestational age of a specific inflammation-related protein
      on 2 separate days a week apart during the first 2 postnatal weeks. We first
      assessed the risk of brain damage indicators by comparing 1) neonates who had HTT
      to those without (regardless of ISSI) and 2) neonates with HTT only, ISSI only,
      or HTT+ISSI to those who were exposed to neither HTT nor ISSI. RESULTS: In
      univariable models that compared those with HTT to those without, HTT was not
      significantly associated with any indicator of brain damage. In models that
      compared HTT only, ISSI only, and HTT+ISSI to those with neither, children with
      ISSI only or with HTT+ISSI were at significantly higher risk of ventriculomegaly
      [odds ratios (ORs) 2-6], whereas those with HTT only were at significantly
      reduced risk of a hypoechoic lesion (ORs 0.2-0.4). Children with HTT only had a
      higher risk of quadriparesis and those with ISSI alone had a higher risk of
      hemiparesis (ORs 1.6-2.4). Elevated risk of a very low mental development score
      was associated with both ISSI only and HTT+ISSI, whereas a very low motor
      development score and microcephaly were associated with HTT+ISSI. CONCLUSIONS:
      The association of HTT with increased or decreased risk of indicators of brain
      damage depends on the presence or absence of ISSI.

PMID- 24897398
TI  - Early indicators of severity and construction of a risk model for prognosis based
      upon laboratory parameters in patients with hemorrhagic fever with renal
      syndrome.
AB  - BACKGROUND: The objective of this study was to explore the role of laboratory
      parameters as early indicators of severity and as effective predictors of
      prognosis in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS:
      A total of 356 patients were enrolled in this study and were divided into mild,
      moderate, severe and critical types according to the clinical classification of
      HFRS. The levels of 12 routinely tested laboratory parameters during the acute
      stage among the four types were compared. The predictive values of the laboratory
      parameters for prognosis were analyzed, and a risk model for prognosis based upon
      the parameters was constructed. RESULTS: The levels of white blood counts (WBC),
      platelets (PLT), aspartate aminotransferase (AST), albumin (ALB), blood urea
      nitrogen (BUN), serum creatinine (Scr), prothrombin time (PT) and activated
      partial thromboplastin time (APTT) demonstrated significant differences among the
      four types (p<0.001); WBC, AST, PT and fibrinogen (Fib) were major independent
      risk factors for death; WBC, AST, PT and Fib used in combination were better for
      predicting prognosis than single parameters used alone (p<0.001). CONCLUSIONS:
      Some routinely tested laboratory parameters can be beneficial as early indicators
      of severity of HFRS. Using a combination of WBC, AST, PT and Fib to predict the
      outcome in patients with HFRS exhibited acceptable diagnostic capability.

PMID- 24897399
TI  - Adopting European Network for Health Technology Assessments (EunetHTA) core model
      for diagnostic technologies for improving the accuracy and appropriateness of
      blood gas analyzers' assessment.
AB  - BACKGROUND: Point-of-care testing (POCT) is a successful methodology for meeting
      clinical expectations of rapid and accurate results. Scientific literature has
      moreover highlighted and confirmed the necessity of individuating the best
      technological solution, in accordance with clinical requirements and
      contextualized to the whole health organization, where it will be implemented.
      Health Technology Assessment (HTA) can assist in reaching an appropriate and
      contextualized decision on a health technology. The aim of this study is to adapt
      a HTA core model for improving the evaluation of a POCT technology: blood gas
      analyzers. METHODS: The European Network for Health Technology Assessment
      (EUnetHTA) core model for diagnostic technologies was applied for evaluating
      globally marketed blood gas analyzers. Evaluation elements were defined according
      to available literature and validated using the Delphi method. RESULTS: A HTA
      model of 71 issues, subdivided into 26 topics and 10 domains, was obtained by
      interviewing 11 healthcare experts over two rounds of Delphi questionnaires. Ten
      context parameters were identified in order to define the initial scenario from
      which the technology assessment was to begin. CONCLUSIONS: The model presented
      offers a systematic and objective structure for the evaluation of blood gas
      analyzers, which may play a guidance role for healthcare operators approaching
      the evaluation of such technologies thus improving, in a contextualized fashion,
      the appropriateness of purchasing.

PMID- 24897400
TI  - European multicenter analytical evaluation of the Abbott ARCHITECT STAT high
      sensitive troponin I immunoassay.
AB  - BACKGROUND: International recommendations highlight the superior value of cardiac
      troponins (cTns) for early diagnosis of myocardial infarction along with
      analytical requirements of improved precision and detectability. In this
      multicenter study, we investigated the analytical performance of a new high
      sensitive cardiac troponin I (hs-cTnI) assay and its 99th percentile upper
      reference limit (URL). METHODS: Laboratories from nine European countries
      evaluated the ARCHITECT STAT high sensitive troponin I (hs-TnI) immunoassay on
      the ARCHITECT i2000SR/i1000SR immunoanalyzers. Imprecision, limit of blank (LoB),
      limit of detection (LoD), limit of quantitation (LoQ) linearity of dilution,
      interferences, sample type, method comparisons, and 99th percentile URLs were
      evaluated in this study. RESULTS: Total imprecision of 3.3%-8.9%, 2.0%-3.5% and
      1.5%-5.2% was determined for the low, medium and high controls, respectively. The
      lowest cTnI concentration corresponding to a total CV of 10% was 5.6 ng/L. Common
      interferences, sample dilution and carryover did not affect the hs-cTnI results.
      Slight, but statistically significant, differences with sample type were found.
      Concordance between the investigated hs-cTnI assay and contemporary cTnI assay at
      99th percentile cut-off was found to be 95%. TnI was detectable in 75% and 57% of
      the apparently healthy population using the lower (1.1 ng/L) and upper (1.9 ng/L)
      limit of the LoD range provided by the ARCHITECT STAT hs-TnI package insert,
      respectively. The 99th percentile values were gender dependent. CONCLUSIONS: The
      new ARCHITECT STAT hs-TnI assay with improved analytical features meets the
      criteria of high sensitive Tn test and will be a valuable diagnostic tool.

PMID- 24897401
TI  - Presepsin as a potential marker for bacterial infection relapse in critical care
      patients. A preliminary study.
AB  - BACKGROUND: Systemic bacterial infection carries a high risk of mortality in
      critical care patients. Improvements in diagnostic procedures are required for
      effective management of sepsis. Recently, the soluble CD14 subtype, or presepsin,
      has been suggested as a reliable marker of sepsis, and we set out to compare its
      diagnostic performance with that of procalcitonin (PCT). We focused on a cohort
      of septic patients who, during their hospitalization, relapsed after a period of
      clinical relief from symptoms. METHODS: In total 21 adult patients were studied
      during their hospitalization in the Critical Care Unit of Policlinico Umberto I
      hospital; 74 plasma samples were collected at multiple time points, and presepsin
      levels were measured using a PATHFAST analyzer. RESULTS: Presepsin and PCT were
      significantly lower in healthy controls than in sepsis or severe sepsis
      (p<0.001), both enabled a significant difference to be detected between systemic
      inflammatory response syndrome (SIRS) and severe sepsis (p<0.05). The area under
      the curve (AUC) calculated from the receiver operating characteristic (ROC) curve
      analysis was 0.888 for presepsin and 0.910 for PCT. In those patients in whom a
      clinical recurrence of sepsis was observed, while PCT levels normalized during
      the transient remission phase, presepsin levels (>1000 pg/mL) remained high.
      CONCLUSIONS: This study confirms the importance of monitoring a combination of
      several biomarkers in order to obtain a reliable diagnosis. Maximal presepsin
      levels could alert clinicians not to suspend antibiotic treatments and to
      carefully monitor septic patients' state of health, even after clinical symptoms
      have disappeared and PCT levels returned to normal.

PMID- 24897403
TI  - Role of presepsin for the evaluation of sepsis in the emergency department.
AB  - Sepsis, severe sepsis and septic shock are among the most common conditions
      handled in the emergency department (ED). According to new Sepsis Guidelines,
      early diagnosis and treatment are the keys to improve survival. Plasma C-reactive
      protein (CRP) and procalcitonin (PCT) levels, when associated with documented or
      suspected infection, are now part of the definitions of sepsis. Blood culture is
      the gold standard method for detecting microorganisms but it requires too much
      time for results to be known. Sensitive biomarkers are required for early
      diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase
      proteins synthesized by the liver: it has a great sensitivity but a very poor
      specificity for bacterial infections. Moreover, the evolution of sepsis does not
      correlate with CRP plasma changes. In recent years PCT has been widely used for
      sepsis differential diagnosis, because of its close correlation with infections,
      but it still retains some limitations and false positivity (such as in multiple
      trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a
      novel and promising biomarker that has been shown to increase significantly in
      patients with sepsis, in comparison to the healthy population. Studies pointed
      out the capability of this biomarker for diagnosing sepsis, assessing the
      severity of the disease and providing a prognostic evaluation of patient outcome.
      In this mini review we mainly focused on presepsin: we evaluate its diagnostic
      and prognostic roles in patients presenting to the ED with systemic inflammatory
      response syndrome (SIRS), suspected sepsis or septic shock.

PMID- 24897404
TI  - The future of the laboratory information system - what are the requirements for a
      powerful system for a laboratory data management?

PMID- 24897402
TI  - The relationship between the Spine Deformity Index, biochemical parameters of
      bone metabolism and vascular calcifications: results from the Epidemiological
      VERtebral FRACtures iTalian Study (EVERFRACT) in dialysis patients.
AB  - BACKGROUND: The Spine Deformity Index (SDI) is a measure of vertebral fractures
      (VFs), providing information on both their number and severity. METHODS: We
      evaluated the relationships between SDI and clinical, biochemical and arterial
      calcification parameters in 387 hemodialysis (HD) patients. VFs, assessed by
      quantitative vertebral morphometry, and vascular calcifications were identified
      in the same lateral spinal X-ray. To improve the detection of fracture severity,
      we created a corrected SDI (c-SDI), by dividing SDI for the number of VFs. We
      assessed routine biochemistry, bone-Gla-protein (BGP), undercaboxylated BGP
      (ucBGP), and matrix-Gla-protein (MGP). RESULTS: VFs prevalence was 55.3%. HD
      patients with a SDI >1 were more frequently males (p<0.05), and had lower BGP
      (p<0.01). Patients with a c-SDI >1 had higher LDL-cholesterol (p<0.05) and lower
      ucBGP (p<0.05) and MGP (p<0.05). Calcifications of the abdominal aorta (AAoC)
      were more frequent in patients with SDI >1 (p<0.05) and with c-SDI >1 (p<0.05).
      Multivariate logistic regression showed that male sex (OR 1.86, CI 1.20-2.91),
      age (OR 1.03, CI 1.01-1.05) and albumin >=3.5 g/dL (OR 0.54, CI 0.31-0.93) were
      predictors of a SDI >1. Age (OR 1.05, CI 1.03-1.07), LDL-cholesterol (OR 1.74, CI
      1.04-2.92) and ucBGP (OR 0.35, CI 0.18-0.70) were associated with c-SDI >1.
      CONCLUSIONS: We conclude that the severity of VFs was associated with age,
      atherogenic factors and bone metabolism markers.

PMID- 24897405
TI  - Red blood cell distribution width is significantly associated with aging and
      gender.

PMID- 24897406
TI  - Hypernatraemia in disguise.

PMID- 24897407
TI  - False-positive D-dimer result in a latex-enhanced immunoassay caused by
      interfering human anti-mouse antibodies.

PMID- 24897408
TI  - Colorectal cancer and screening programs: not only analytical issues.

PMID- 24897409
TI  - A multi-collaborative ambient assisted living service description tool.
AB  - Collaboration among different stakeholders is a key factor in the design of
      Ambient Assisted Living (AAL) environments and services. Throughout several AAL
      projects we have found repeated difficulties in this collaboration and have
      learned lessons by the experience of solving real situations. This paper
      highlights identified critical items for collaboration among technicians, users,
      company and institutional stakeholders and proposes as a communication tool for a
      project steering committee a service description tool which includes information
      from the different fields in comprehensible format for the others. It was first
      generated in the MonAMI project to promote understanding among different
      workgroups, proven useful there, and further tested later in some other smaller
      AAL projects. The concept of scalable service description has proven useful for
      understanding of different disciplines and for participatory decision making
      throughout the projects to adapt to singularities and partial successes or faults
      of each action. This paper introduces such tool, relates with existing
      methodologies in cooperation in AAL and describes it with a example to offer to
      AAL community. Further work on this tool will significantly improve results in
      user-centered design of sustainable services in AAL. 

PMID- 24897410
TI  - Finite-size effects and analytical modeling of electrostatic force microscopy
      applied to dielectric films.
AB  - A numerical analysis of the polarization force between a sharp conducting probe
      and a dielectric film of finite lateral dimensions on a metallic substrate is
      presented with the double objective of (i) determining the conditions under which
      the film can be approximated by a laterally infinite film and (ii) proposing an
      analytical model valid in this limit. We show that, for a given dielectric film,
      the critical diameter above which the film can be modeled as laterally infinite
      depends not only on the probe geometry, as expected, but mainly on the film
      thickness. In particular, for films with intermediate to large thicknesses (>100
      nm), the critical diameter is nearly independent from the probe geometry and
      essentially depends on the film thickness and dielectric constant following a
      relatively simple phenomenological expression. For films that can be considered
      as laterally infinite, we propose a generalized analytical model valid in the
      thin-ultrathin limit (<20-50 nm) that reproduces the numerical calculations and
      the experimental data. Present results provide a general framework under which
      accurate quantification of electrostatic force microscopy measurements on
      dielectric films on metallic substrates can be achieved. 

PMID- 24897411
TI  - Exercise-induced bone formation is poorly linked to local strain magnitude in the
      sheep tibia.
AB  - Functional interpretations of limb bone structure frequently assume that
      diaphyses adjust their shape by adding bone primarily across the plane in which
      they are habitually loaded in order to minimize loading-induced strains. Here, to
      test this hypothesis, we characterize the in vivo strain environment of the sheep
      tibial midshaft during treadmill exercise and examine whether this activity
      promotes bone formation disproportionately in the direction of loading in
      diaphyseal regions that experience the highest strains. It is shown that during
      treadmill exercise, sheep tibiae were bent in an anteroposterior direction,
      generating maximal tensile and compressive strains on the anterior and posterior
      shaft surfaces, respectively. Exercise led to significantly increased periosteal
      bone formation; however, rather than being biased toward areas of maximal strains
      across the anteroposterior axis, exercise-related osteogenesis occurred primarily
      around the medial half of the shaft circumference, in both high and low strain
      regions. Overall, the results of this study demonstrate that loading-induced bone
      growth is not closely linked to local strain magnitude in every instance.
      Therefore, caution is necessary when bone shaft shape is used to infer functional
      loading history in the absence of in vivo data on how bones are loaded and how
      they actually respond to loading. 

PMID- 24897412
TI  - A new naphthol from the twigs and leaves of Pterospermum yunnanense.
AB  - A new naphthol, 7-hydroxy-6-methyl-1-naphthoic acid methyl ester (1), together
      with eight known compounds, 6-hydroxy-7-(hydroxymethyl)-1-isopropyl-4-methyl
      naphthalene (2), alpha-hydroxyacetosyringone (3), hexadecyl ferulate (4),
      scoparone (5), (+)-syringaresinol (6), stigmast-1,5-dien-3beta-ol (7), beta
      sitosterol (8) and daucosterol (9), were isolated from the twigs and leaves of
      Pterospermum yunnanense Hsue. Their structures were elucidated by using
      spectroscopic analysis. All the compounds were isolated for the first time from
      P. yunnanense Hsue. Compound 1 was assessed for its cytotoxicity against five
      human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result
      showed that it has no activity. 

PMID- 24897413
TI  - Mimetic behavior of rats in flavor aversion learning.
AB  - Rats exposed to odor (almond), taste (saccharin) or an odor/taste-compound
      (almond/ saccharin) in a one-trial conditioning were subsequently poisoned with
      lithium chloride either 5 min (Ex) or 16 h (Co) after drinking. We measured
      various behavioral CRs elicited by these conditioned stimuli. All stimuli and
      compounds produced strong flavor aversions and elicited a pattern of agitated
      behavior characterized by increased general activity, rearing, and the specific
      mimetic response 'gaping' in the experimental groups. No comparable patterns were
      observed in the control groups. In the compound-experimental group an
      overshadowing effect for the odor component by the new taste was found. However,
      odor in this condition still elicited somewhat reduced drinking and the typical
      aversive reaction pattern. Behaviors induced by pairing odor with illness were
      more strongly controlled by the presence of the poisoned odor in the compound
      condition than in the odor condition. The compound experimental group
      discriminated more strongly, in general, behaviors and in their mimetic responses
      between the time when odor was presented or not in a test procedure, which
      alternated poisoned odor and air. 

PMID- 24897414
TI  - Defensive aspects of burrowing behavior in rats (Rattus Norvegicus): A
      descriptive and correlational study.
AB  - Several burrowing behavioral characteristics of five different, genetically
      biased, strains of rats (Rattus norvegicus), with each showing various defensive
      and open-field behaviors, were investigated to examine the defensive aspects of
      burrowing behavior. The strains used were the Tsukuba High- and Low-Emotional
      (THE and TLE), F344/DuCrj (F344), Long Evans (LE), and the Wistar-Imamichi/lar
      (WI). The THE and LE strains showed significantly shorter burrowing latency, more
      digging activity, and longer length burrows, with most rats escaping into their
      burrows at a loud crash sound. On the other hand, the TLE and WI stains displayed
      significantly longer burrowing latency, less digging activity, and shorter length
      burrows, with only a few rats escaping. These findings showed the consistency
      among the burrowing characteristics and a close relationship between burrowing
      and escape. The F344 strain, on the contrary, showed a shorter burrowing latency
      and more digging activity than the TLE and WI strains (although similar length
      burrows), yet few rats escaped. Digging, burying, open-field defecation, and re
      emergency latency after escape correlated highly with each other, possibly
      suggesting their defensive nature. In conclusion, it is possible that burrowing
      behavior is a species-specific defense reaction (SSDR), yet factors involved in
      burrowing seem to be complicated, with more extensive studies therefore required.

PMID- 24897415
TI  - Methodological improvements for the study of reconciliation.
AB  - The present paper suggests methodological improvements for the study of
      reconciliation, i.e. affiliative interactions between former opponents shortly
      after agonistic conflicts. Three methods have been suggested to determine whether
      post-conflict affiliation between former opponents is higher than what would be
      expected by chance. Two of these methods may fail to find this higher level when
      the analyses are based on long-lasting observations. The third method, however,
      solves this potential shortcoming by identifying the 'relevant' duration of the
      observations to be considered. We also emphasize the importance of distinguishing
      post-conflict affiliative interactions on the basis of their timing following a
      conflict in order to examine their conciliatory functions. Finally we suggest a
      correction of the conciliatory tendency, a measure used to compare the frequency
      of reconciliation between dyads of individuals that may have different baseline
      levels of affiliation. A comparison between the original measure and the
      corrected one shows that only the latter is independent of the baseline level of
      affiliation and is, therefore, more suitable for the study of intra- and inter
      specific differences in the frequency of reconciliation. 

PMID- 24897416
TI  - Properties of time-place learning by pigeons, Columba livia.
AB  - Pigeons received discrimination training in which food reinforcement for key
      pecking was conditional upon both spatial and temporal cues. In Experiment 1 food
      was available for periods of 15 min at each of four locations (pecking keys)
      during a 60-min trial. However, unlike the procedures used in a previous
      experiment (Wilkie and Willson, 1992, Experiment 2), food availability did not
      change over time from one location to the next in a simple monotonic (e.g.
      counterclockwise) manner. Despite making food available in a figure-eight
      pattern, pigeons' key pecking was still jointly controlled by the spatial and
      temporal cues. Experiment 2 sought evidence on the nature of the timing mechanism
      underlying this behavior. The results of manipulations such as turning all of the
      keys off, and removing and replacing the subjects, suggested that a stopwatch
      like mechanism with properties of stop/restart and reset underlies pigeons' time
      place learning, at least with the temporal parameters used in these experiments.
      This finding contrasts with others in the literature that suggests that a
      circadian mechanism controls birds visits to different spatial locations. It will
      be important in future research to determine the relations between the different
      timing systems involved in time-place learning by foragers. 

PMID- 24897417
TI  - Identifying location by dead reckoning and external cues.
AB  - Golden hamsters can orient towards specific points in their environment using
      location- based visual cues and/or dead reckoning based on vestibular and
      proprioceptive signals. The relative weight of these different kinds of
      information was investigated in an apparatus consisting of three identical,
      square compartments joined by tunnels, with the subject's own nest box at one
      end. Each compartment contained a feeding site and a weak light spot, the
      relation between the feeding site and the light spot being different in the three
      compartments. The animals were trained to hoard food in succession from the three
      feeding locations, in darkness. During test trials, the light spots were either
      suppressed or moved to new locations, thus being set in conflict with other kinds
      of spatial information. In the majority of trials, the subjects proceeded fairly
      directly to the feeding places, independently of the presence and position of the
      light spots. This performance may be explained through rote motor learning, which
      may be initiated with respect to tactile cues previously associated to the goal.
      However, more flexible, indirect trajectories towards the goal suggest that the
      subjects kept track of their location within the test space and therefore
      depended simultaneously on dead reckoning and a map. A control experiment in
      which the goals were moved along with the visual cues excluded the use of
      olfactory cues from the food source and confirmed the role of dead reckoning. 

PMID- 24897418
TI  - A method of modelling time dependent data: swimming in guppies (Poecilia
      Reticulata) under threat of a predator.
AB  - The use of statistics that assume independence between observations may not be an
      adequate tool in the analysis of how prey fish co-ordinate their swimming when
      inspecting piscine predators. This is mainly caused by the fact that continuity
      is an inevitable feature of locomotion. Thus, if one takes observations at close
      intervals, the assumption of independence will probably be violated, while
      observations taken too far apart may lose significant information of what goes on
      in between. In this paper we present one way of dealing with these problems and
      demonstrate what may come out when applied to empirical data of predator
      inspection in fish. The method models measurements taken at equispaced points in
      time as dynamic systems of simultaneous stochastic difference equations, and may
      well be applied in general to auto- and cross-correlated data. A full account of
      statistical procedures and how to estimate the order of difference presented in
      an appendix. Swimming trajectories, represented as successive distances to
      predators at intervals of 2 s, were obtained from paired male guppies inspecting
      piscine predators. Dynamic models of swimming were then estimated and used for
      quantifying causes of locomotion that relates to inertia of own swimming, to
      motion of co-inspectors, and to independent causes generated elsewhere. The
      derived models complied with second order systems in 9 out of the 10 fish that
      were investigated. Feed-back relations within co-inspectors varied between pairs,
      but none of the fish moved independently of its partner. All models may be
      interpreted in terms of interacting attracting/repelling 'forces' between each
      prey fish and the predator. The way swimming by a particular fish affected co
      inspectors was further analysed. Mean properties of this influence revealed that
      even when partners lagged behind inspecting individuals, they mostly behaved so
      as to make the leading fish approach the predators even further. This finding
      suggests other behavioural strategies to be involved than those assumed
      previously, and one alternative is discussed. 

PMID- 24897419
TI  - Responses of maternal and non-maternal ewes to social and mother-young
      separation.
AB  - The response to social deprivation in non-maternal non-pregnant ewes was compared
      with that in post-parturient ewes kept with their lamb. In addition, the response
      to separation from the lamb was investigated in lactating ewes at times ranging
      from 24 h to 2 months post partum. Ewes were observed for 5 min in a 2 * 4 m pen,
      either in the presence or in the absence of 4 adult conspecifics, after which
      lactating ewes were deprived of their lamb for a further 5 min. Results indicate
      that mothers of lambs did not react to isolation from adult conspecifics 24 h
      after parturition, in contrast to non-lactating females, which showed significant
      increases in high-pitch bleating, motor activity and eliminative behaviours (p <
      0.05 in all cases). On the other hand maternal females reacted very strongly to
      isolation from their lamb. For some behaviours (high-pitch bleats, nosings)
      response to separation remained quite high even in mothers of two-month-old
      lambs. However a clear decrease in responses was noted in most behaviours during
      the first month, and in some cases during the first week of lactation. Overall
      these results indicate that there is a dramatic decline in gregariousness during
      the peripartum period. The comparison of postpartum changes in maternal responses
      to lamb separation in isolated and grouped ewes suggests a combination of
      decreased maternal response to separation and recovery of usual social tendencies
      in the first weeks of lactation. Finally our results also indicate that the
      nosing of inanimate substrates such as ground and walls generally observed in
      open-field type tests may be related to social deprivation. 

PMID- 24897421
TI  - Bases neurologiques des comportements (Neurological bases of behaviours) M.
      Habib. 1993. 2nd edn. Editions Masson, Paris.

PMID- 24897420
TI  - Trail-laying and recruitment to sugary foods by foraging red wood-ants Formica
      aquilonia Yarrow (Hymenoptera: Formicidae).
AB  - The use of trail communication by red wood-ants, Formica aquilonia Yarrow,
      foraging to sugar baits, was investigated by providing a laboratory colony with
      aqueous sucrose at two novel feeding sites, with a third site, providing no food,
      as a control. During trials, the sites were connected to the nest by paper
      bridges which were replaced between treals. One of the sites providing food was
      reached by a two-way bridge, as was the control. The second baited site was
      reached by a one-way bridge: this site had a one-way exit from which returning
      foragers dropped to the nest. Hence, if returning foragers laid a trail from a
      bait, they would do so on the two-way bridge, but not on the one-way bridge by
      which foragers did not return, nor on the bridge to the unbaited site. This would
      lead to a greater increase in foraging traffic on the two-way bridge, relative to
      that on the other two bridges, during a given trial. Each trial was preceded by a
      30-min counting session with no baits present, to establish the mean number of
      ants arriving per minute on each bridge through random exploration. After
      provision of food, ants arriving on each bridge per minute were counted in four
      separate 30-min sessions: each count was then converted to a proportion of the
      original mean traffic on that bridge, and the change in traffic with time was
      compared between bridges using analysis of variance. The increase in traffic was
      significantly greater on the two-way bridge than on the control and one-way
      bridges, indicating that replete ants returning from the bait left a trail on the
      homeward route, which other ants subsequently followed. 

PMID- 24897422
TI  - Physiologie des regulations (Physiology of regulations) E. Schoffeniels and G.
      Moonen. 1993. 2nd edition (revised and updated). Collection enseignement des
      sciences de la vie Editions Masson, Paris.

PMID- 24897424
TI  - Multiported pulsed valve interface for a linear quadrupole ion trap mass
      spectrometer to enable rapid screening of multiple functional-group selective ion
      molecule reactions.
AB  - Ion-molecule reactions provide a powerful tool for structural elucidation of
      ionized pharmaceutical analytes in tandem mass spectrometry. However, all
      previous interfaces for the introduction of reagents for ion-molecule reactions
      have utilized a single reagent approach. In this study, a multiported pulsed
      valve system was designed and characterized for rapid introduction of three
      neutral reagents into a linear quadrupole ion trap. Additionally, automatic
      triggering was used to allow for the introduction of the reagents on a
      chromatographic time scale. This system enables automatic, high throughput
      screening of complex mixtures by using at least three different ion-molecule
      reactions. Further, rapid testing of new neutral reagents is also possible. 

PMID- 24897423
TI  - Catalytic activity of cGMP-dependent protein kinase type I in intact cells is
      independent of N-terminal autophosphorylation.
AB  - Although cGMP-dependent protein kinase type I (cGKI) is an important mediator of
      cGMP signaling and upcoming drug target, its in vivo-biochemistry is not well
      understood. Many studies showed that purified cGKI autophosphorylates multiple
      sites at its N-terminus. Autophosphorylation might be involved in kinase
      activation, but it is unclear whether this happens also in intact cells. To study
      cGKI autophosphorylation in vitro and in vivo, we have generated phospho-specific
      antisera against major in vitro-autophosphorylation sites of the cGKI isoforms,
      cGKIalpha and cGKIbeta. These antisera detected specifically and with high
      sensitivity phospho-cGKIalpha (Thr58), phospho-cGKIalpha (Thr84), or phospho
      cGKIbeta (Thr56/Ser63/Ser79). Using these antisera, we show that ATP-induced
      autophosphorylation of cGKI in purified preparations and cell extracts did
      neither require nor induce an enzyme conformation capable of substrate
      heterophosphorylation; it was even inhibited by pre-incubation with cGMP.
      Interestingly, phospho-cGKI species were not detectable in intact murine cells
      and tissues, both under basal conditions and after induction of cGKI catalytic
      activity. We conclude that N-terminal phosphorylation, although readily induced
      in vitro, is not required for the catalytic activity of cGKIalpha and cGKIbeta in
      vivo. These results will also inform screening strategies to identify novel cGKI
      modulators. 

PMID- 24897425
TI  - The importance of preventing work-related disability.

PMID- 24897426
TI  - An approach for Web service selection based on confidence level of decision
      maker.
AB  - Web services today are among the most widely used groups for Service Oriented
      Architecture (SOA). Service selection is one of the most significant current
      discussions in SOA, which evaluates discovered services and chooses the best
      candidate from them. Although a majority of service selection techniques apply
      Quality of Service (QoS), the behaviour of QoS-based service selection leads to
      service selection problems in Multi-Criteria Decision Making (MCDM). In the
      existing works, the confidence level of decision makers is neglected and does not
      consider their expertise in assessing Web services. In this paper, we employ the
      VIKOR (VIsekriterijumskoKOmpromisnoRangiranje) method, which is absent in the
      literature for service selection, but is well-known in other research. We propose
      a QoS-based approach that deals with service selection by applying VIKOR with
      improvement of features. This research determines the weights of criteria based
      on user preference and accounts for the confidence level of decision makers. The
      proposed approach is illustrated by an example in order to demonstrate and
      validate the model. The results of this research may facilitate service consumers
      to attain a more efficient decision when selecting the appropriate service. 

PMID- 24897427
TI  - CD8+ TCR transgenic strains expressing public versus private TCR targeting the
      respiratory syncytial virus K(d)M2(82-90) epitope demonstrate similar functional
      profiles.
AB  - Our previous work has characterized the functional and clonotypic features of two
      respiratory syncytial virus (RSV) epitope-specific T cell responses in mice.
      Following single-cell sequencing, we selected T cell receptor sequences to
      represent both a public and a private clone specific for the dominant K(d)M2(82
      90) epitope for the generation of T cell receptor transgenic (TCR Tg) mice. We
      evaluated cells from these TCR Tg strains for three major functions of CD8+ T
      cells: proliferation, cytokine production and cytolytic activity. In vitro
      comparisons of the functional characteristics of T cells from the newly-generated
      mice demonstrated many similarities in their responsiveness to cognate antigen
      stimulation. Cells from both TRBV13-1 (private) and TRBV13-2 (public) TCR Tg mice
      had similar affinity, and proliferated similarly in vitro in response to cognate
      antigen stimulation. When transferred to BALB/c mice, cells from both strains
      demonstrated extensive proliferation in mediastinal lymph nodes following RSV
      infection, with TRBV13-2 demonstrating better in vivo proliferation. Both strains
      similarly expressed cytokines and chemokines following stimulation, and had
      similar Granzyme B and perforin expression, however cells expressing TRBV13-1
      demonstrated better cytolytic activity than TRBV13-2 cells. These new, well
      characterized mouse strains provide new opportunities to study molecular
      mechanisms that control the phenotype and function of CD8+ T cell responses.

PMID- 24897432
TI  - VIS-UV ZnCdO/ZnO multiple quantum well nanowires and the quantification of Cd
      diffusion.
AB  - We report on the growth and microstructure analysis of high Cd content ZnCdO/ZnO
      multiple quantum wells (MQW) within a nanowire. Heterostructures consisting of
      ten wells with widths from 0.7 to 10 nm are demonstrated, and show
      photoluminescence emissions ranging from 3.03 to 1.97 eV. The wells with
      thicknesses ?2 nm have high radiative efficiencies compared to the thickest ones,
      consistent with the presence of quantum confinement. However, a nanometric
      analysis of the Cd profile along the heterostructures shows the presence of Cd
      diffusion from the ZnCdO well to the ZnO barrier. This phenomenon modifies the
      band structure and the optical properties of the heterostructure, and is
      considered in order to correctly identify quantum effects in the ZnCdO/ZnO MQWs. 

PMID- 24897430
TI  - Undesired small RNAs originate from an artificial microRNA precursor in
      transgenic petunia (Petunia hybrida).
AB  - Although artificial microRNA (amiRNA) technology has been used frequently in gene
      silencing in plants, little research has been devoted to investigating the
      accuracy of amiRNA precursor processing. In this work, amiRNAchs1 (amiRchs1),
      based on the Arabidopsis miR319a precursor, was expressed in order to suppress
      the expression of CHS genes in petunia. The transgenic plants showed the CHS gene
      silencing phenotype. A modified 5' RACE technique was used to map small-RNA
      directed cleavage sites and to detect processing intermediates of the amiRchs1
      precursor. The results showed that the target CHS mRNAs were cut at the expected
      sites and that the amiRchs1 precursor was processed from loop to base. The
      accumulation of small RNAs in amiRchs1 transgenic petunia petals was analyzed
      using the deep-sequencing technique. The results showed that, alongside the
      accumulation of the desired artificial microRNAs, additional small RNAs that
      originated from other regions of the amiRNA precursor were also accumulated at
      high frequency. Some of these had previously been found to be accumulated at low
      frequency in the products of ath-miR319a precursor processing and some of them
      were accompanied by 3'-tailing variant. Potential targets of the undesired small
      RNAs were discovered in petunia and other Solanaceae plants. The findings draw
      attention to the potential occurrence of undesired target silencing induced by
      such additional small RNAs when amiRNA technology is used. No appreciable
      production of secondary small RNAs occurred, despite the fact that amiRchs1 was
      designed to have perfect complementarity to its CHS-J target. This confirmed that
      perfect pairing between an amiRNA and its targets is not the trigger for
      secondary small RNA production. In conjunction with the observation that amiRNAs
      with perfect complementarity to their target genes show high efficiency and
      specificity in gene silencing, this finding has an important bearing on future
      applications of amiRNAs in gene silencing in plants. 

PMID- 24897435
TI  - Space use and foraging movements in the American red squirrel (Tamiasciurus
      hudsonicus).
AB  - This study deals with the movements of two American red squirrels (Tamiasciurus
      hudsonicus) in their home ranges from late spring to early autumn in a deciduous
      coniferous forest in Quebec. During 70 six-hour tracking sessions, the type of
      behaviour exhibited at any place, and its terrestrial or arboreal occurrence,
      were recorded. Spatio-temporal structure of the squirrels' home ranges were
      analysed in relation to vegetation type and food availability. Although American
      red squirrels are known to be mainly adapted to coniferous forests, they also
      exploit deciduous areas when these areas become productive. Half of the
      squirrels' activity time was devoted to feeding or to searching for food, and a
      third was devoted to moving about. Movements were performed mainly on the ground,
      with a rate of about 0.5 km per activity hour, and appeared to be mainly
      organized around the locations of food caches and food-providing sites. 

PMID- 24897431
TI  - Inhibitor ranking through QM based chelation calculations for virtual screening
      of HIV-1 RNase H inhibition.
AB  - Quantum mechanical (QM) calculations have been used to predict the binding
      affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM
      based chelation calculations show improved binding affinity prediction for the
      inhibitors compared to using an empirical scoring function. Furthermore, full
      protein fragment molecular orbital (FMO) calculations were conducted and
      subsequently analysed for individual residue stabilization/destabilization energy
      contributions to the overall binding affinity in order to better understand the
      true and false predictions. After a successful assessment of the methods based on
      the use of a training set of molecules, QM based chelation calculations were used
      as filter in virtual screening of compounds in the ZINC database. By this, we
      find, compared to regular docking, QM based chelation calculations to
      significantly reduce the large number of false positives. Thus, the computational
      models tested in this study could be useful as high throughput filters for
      searching HIV-1 RNase H active-site molecules in the virtual screening process. 

PMID- 24897436
TI  - Transfer of oddity-from-compound samples in the pigeon: Some assembly required.
AB  - Experiment 1 trained three pigeons on a six-key oddity-from-sample procedure. At
      trial onset, one of two compound color-form sample stimuli was presented (a white
      'X' on a red background or a white circle on a green background). Every second
      peck on the sample key lighted another comparison stimulus up to a maximum of
      four stimuli (red, green, circle and X). A peck on the two keys that presented
      non-matching color and form stimuli, relative to the compound sample, lighted a
      reinforcement key. A peck to this key produced grain. Errors darkened the
      comparison keys and repeated the trial. The birds learned to perform without
      error during 70-80% of the session trials, and showed transfer of oddity
      performance to eight novel compound samples. Experiment 2 presented the pigeons
      with novel combinations of familiar color and form stimuli. Each bird performed
      well above chance indicating that their behavior was under the control of an
      oddity concept. 

PMID- 24897438
TI  - Modelling timing performance on the peak procedure.
AB  - Computer simulations based on the Scalar Expectancy Theory (SET) and the
      connectionist model of Church and Broadbent (1990) were run to match data sets
      from the peak procedure. On the peak procedure, a light or tone usually signals a
      reward for a response after a fixed interval (FI), but occasionally, the signal
      is left on for a long time and reward is withheld. On such a test, a period of
      high rate of responding (run) is sandwiched between periods of low rates of
      responding. Models were run to match the means and standard deviations of the
      start, the end, the middle, and the duration of the run, as well as the
      correlations among them. On a trial, the models based on SET determined the start
      and the end of the run according to a memory of expected time of reward and one
      or two thresholds. Models sampling two thresholds, with both difference and ratio
      comparison rules, fit the data well. In the connectionist models the memory was a
      matrix of vector autocorrelations, with a vector representing a clock reading on
      a set of oscillators. The thresholds were each an angle between the clock vector
      and a comparison vector derived from memory. These models did not fare well. 

PMID- 24897437
TI  - A laboratory study of social behaviour of pairs of females during the
      reproductive season in Spermophilus spilosoma and Spermophilus mexicanus.
AB  - Spermophilus spilosoma and Spermophilus mexicanus are closely related species
      with a low degree of sociality. They are sympatric in the Bolson de Mapimi
      (Chihuahua Desert, Mexico), where they occupy similar ecological niches. In
      Sciurid rodents, advanced social structures may have evolved through the
      formation of sedentary female groups. The purpose of this study is to compare the
      ability of S. spilosoma and S. mexicanus females to cohabit with another
      conspecific female under space constraints during the mating period. The
      stability of the female relationships was tested by introducing a male of the
      same species. In both species, females managed to cohabit under space constraints
      with a low level of agonism. Nevertheless, an increase of defensive behaviour and
      a decrease of amicable behaviour were observed during female cohabitation in S.
      spilosoma. Moreover, female S. mexicanus had a higher tolerance index than S.
      spilosoma during this same period. The introduction of a male induced an increase
      of the level of agonism of S. mexicanus females while no reaction was detected in
      S. spilosoma. These differences were discussed in terms of mechanisms which could
      preclude the formation of sedentary social groups of females. 

PMID- 24897439
TI  - Effects of cue manipulation on performance by old and young rats in a test of non
      matching-to-sample.
AB  - In a study of the effects of age on cue utilization, groups of young and old rats
      were administered three versions of a non-matching-to-sample task that could be
      solved only by using spatial stimuli, local stimuli, or response cues
      respectively. The delay between sample and test runs was varied between 0 and 60
      s. The old rats were severely impaired in spatial and local stimulus versions but
      the performance of old and young groups was comparable in the response version of
      the task. In the Response-cue task, where the old rats displayed substantial
      learning, their performance deteriorated more than that of the young rats when
      the delay was increased from 0 to 60 s. 

PMID- 24897440
TI  - Differential inhibition using contextual stimuli.
AB  - The present experiments examined whether external contextual stimuli can acquire
      inhibitory properties through a simple differential context-reinforcement
      procedure. Rats first received discrimination training sessions in which an
      electric footshock was consistently delivered in one context, but not in a
      second, different context. In Experiments 1A and 1B, summation and retardation
      tests were subsequently performed using the non-reinforced context. Each of these
      tests failed to reveal contextual conditioned inhibition. In Experiment 2, a
      summation and retardation test were performed using a contextual stimulus that
      was unique to the non-reinforced context. Weak but significant contextual
      inhibition was found. It was suggested that contextual stimuli that are unique to
      the non-reinforced context did acquire inhibitory strength in each experiment,
      but that in Experiments 1A and 1B, expression of this inhibition during testing
      had been masked by the concurrent presence of excitation from elements that the
      non-reinforced context had in common with the reinforced context. 

PMID- 24897441
TI  - Transitive responding in pigeons: influences of stimulus frequency and
      reinforcement history.
AB  - Fersen et al. (1991) (J. Exp. Psychol.: Anim. Behav. Process., 17: 334-341)
      trained pigeons to discriminate four overlapping pairs of stimuli A + B -, B + C 
      , C + D - and D + E - (+ rewarded, - penalized). When subsequently tested with a
      pair BD the pigeons showed a strong preference for stimulus B. A special value
      transfer theory was offered as an explanation for this transitive responding. A
      simpler reinforcement ratio account based on certain inequalities factually
      affecting the accuracy performance on training pairs is proposed. To explore its
      implications an experiment employing a novel grit-grain conditioning method was
      carried out. The presentation frequencies of the training pairs were biased so
      that the choice accuracies obtained at the end of training were approximately
      equal for all pairs. Testing with pair BD still yielded high preference for B,
      documenting the robustness of the transitive responding phenomenon. When suitably
      adjusted to the training design the reinforcement ratio account was still viable.
      The transitive responding with the BD and other test pairs could also be
      simulated with a simple reinforcement based conditioning model. Some of the
      subjects were then retrained with modified presentation frequencies so that the
      subjects ended up with an even overall exposure to all training pairs. Test pairs
      continued to yield strong transitive responding. It is concluded that this
      behavioral effect is a robust phenomenon which is largely unaffected by training
      design modifications. 

PMID- 24897442
TI  - Auditory discrimination reversal learning and assessment of behavioral
      teratogenesis in rats.
AB  - Qualitative auditory discrimination procedures were used to evaluate
      discrimination acquisition and reversal learning in rats. Twelve adult rats
      prenatally exposed to ethanol (ETOH) and 12 unexposed isocaloric controls (CON)
      were given training with a positively reinforced successive discrimination
      procedure. Most ETOH subjects were impaired relative to CON subjects on accuracy
      during early training sessions and the number of sessions required to meet an 80%
      accuracy criterion. Some ETOH subjects were also impaired on the rate of learning
      over a series of repeated discrimination reversals. Individual differences in
      reversal learning rates varied more widely with ETOH subjects than with CON
      subjects. Our results indicate that the auditory discrimination procedures may
      find application in assessments of behavioral teratogenesis. 

PMID- 24897443
TI  - Differential effects of restraint and novelty on the social behaviour of female
      rats.
AB  - In a previous work, we have described an increase of agonistic behaviour 24 h
      after a single 30-min restraint (RT) in female rats. The present work was aimed
      at assessing whether this effect was actually due to physical immobilization or
      was a mere consequence of the exposure to a novel environment (the restraining
      box in the experimental room). Dioestrous females were either left undisturbed in
      their home cages (Control), restrained (RT), or subjected to the same
      experimental schedule as the restrained ones, but placed in a living cage instead
      of in the restraining device (Novelty). Twenty-four hours after treatment, the
      social behaviour of the experimental females was recorded during a 20-min
      encounter, in a neutral arena, with an unfamiliar conspecific female in the same
      oestrous cycle phase. Novelty did affect behaviour, but in a way completely
      different from RT: while RT increased the frequencies of agonism and other social
      behaviours, novelty caused a selective decrease of agonism. The effects of RT on
      the social behaviour of female rats appear therefore to be specific and
      independent of those caused by novelty. 

PMID- 24897444
TI  - Within-session responding as a function of force required for lever press.
AB  - Four male Sprague-Dawley rats pressed a lever for food reinforcers delivered by a
      multiple variable interval 1-min variable interval 1-min schedule. Components
      alternated every 5 min. The force required to move the lever was 0.25, 0.15,
      1.10, 0.75, and 0.50 N in different conditions. Changes in the force requirement
      did not alter the within-session pattern of responding. These results are
      consistent with other experiments suggesting that muscle warm-up and fatigue are
      not sufficient explanations for the within-session pattern of responding. 

PMID- 24897445
TI  - The behavioural priorities of laying hens: the effect of cost/no cost multi
      choice tests on time budgets.
AB  - A multi-choice situation offering a number of presumably significant
      environmental features may reveal an animal's immediate preferences concerning
      its environment and how it wants to distribute its time budget. In this study the
      time budgets of hens (Gallus gallus domesticus) were examined in a free access
      situation (no cost condition) and in a situation in which there was a cost for
      access (cost condition). The options consisted of six pens that could be entered
      from a middle pen which had no features except for space. The options were: (1)
      food and water; (2) woodchips; (3) grass (turf) or wheat seedlings; (4) a perch;
      (5) a nestbox; (6) a pen facing another pen with familiar hens. In the first
      experiment, hens were given a multi-choice test in a seven pen apparatus. The no
      cost condition gave free access to resources but in the cost condition hens had
      to squeeze through two dowels. The frequency of entering pens and initiating
      behaviours was greatly reduced in the cost condition. In the second experiment,
      hens were tested for their preferences after one of two treatments: (i) 'prior
      access' (and free access) to all pens for 22.5 h; (ii) 'no prior access' where
      hens were housed in a barren pen without food for 22.5 h. The duration of
      agonistic, pace/escape and stretch neck behaviours were greater in the 'no prior
      access' or cost condition. In both experiments, the amount of time pecking and
      scratching in litter did not differ between conditions. Thus, the imposition of a
      cost did not alter the amount of time spent pecking and scratching supporting the
      argument that this behaviour is an ethological need. 

PMID- 24897446
TI  - The behavioural priorities of laying hens: the effects of two methods of
      environment enrichment on time budgets.
AB  - In the first experiment, a comparison was made of the time budgets of laying hens
      (Gallus gallus domesticus) in an enriched condition, in which various objects
      were added to their pen, and an unenriched condition, the same pen but without
      these objects. Assuming a fixed time budget, greater choices in the enriched
      condition would increase some behaviours at the expense of others, providing a
      relative measure of importance. In a second experiment, one group had woodchips
      on the floor with food and the other had woodchips on the floor without food
      (available from a hopper). In the first experiment, frequency of dust-bathing
      decreased in the enriched condition. Hens in the unenriched condition spent more
      time preening, drinking, social pecking at others and being aggressive which also
      increased in the second experiment in the hopper food condition. In both
      experiments, there was no difference in the amount of time feeding and also
      pecking and scratching even though food was not available in the litter in the
      unenriched condition. The results of the second experiment show that feeding on
      the floor alone, i.e., not in combination with environmental enrichment, also
      reduces aggression, whereas it has no influence on social pecking. 

PMID- 24897449
TI  - Current Primatology, Volume I: Ecology and Evolution Edited by B. Thierry, J.R.
      Anderson, J.J. Roeder and N. Herrenschmidt. 398 pp. Universite Louis Pasteur,
      Strasbourg, 1994.

PMID- 24897450
TI  - Current Primatology, Volume II: Social Development, Learning and Behaviour Edited
      by J.J. Roeder, B. Thierry, J.R. Anderson and N. Herrenschmidt. 404 pp.
      Universite Louis Pasteur, Strasbourg, 1994.

PMID- 24897451
TI  - Current primatology, Volume III: Behavioural Neuroscience, Physiology and
      Reproduction Edited by J.R. Anderson, J.J. Roeder, B. Thierry and N.
      Herrenschmidt. 293 pp. Universite Louis Pasteur, Strasbourg, 1994.

PMID- 24897456
TI  - Categories as paradigms for comparative cognition.
AB  - Forming categories is a basic cognitive operation allowing animals to attain
      concepts, i.e. to represent various classes of objects, natural or artificial,
      physical or social. Categories can also be formed about the relations holding
      among these objects, notably similarity and identity. Some of the cognitive
      processes involved in categorisation will be enumerated. Also, special reference
      will be made to a much neglected area of research, that of social
      representations. Here, animals conceive the natural class of their conspecifics
      as well as the relationships established between them in groups. Two types of
      social categories were mentioned: (1) intraspecies recognition including
      recognition of individual conspecifics; and (2) representation of dominance
      hierarchies and of their transitivity in linear orders. 

PMID- 24897457
TI  - Figurative and spatial information and search behavior in dogs (Canis
      familiaris).
AB  - Domestic dogs (Canis familiaris) were administered a variant of the delayed
      matching-to-sample task in which they had to recover a hidden object and in which
      both spatial and figurative information were kept constant at the outset of each
      trial. Thereafter, either spatial (i.e. spatial condition) or figurative cues
      (i.e. figurative condition) became relevant to solve the task. The results
      revealed that dogs rapidly associated a spatial cue with the recovery of the
      object. The discussion emphasizes the role of cognitive and ecological
      constraints to account for the fact that figurative information was not readily
      used as a cue to guide search behavior. 

PMID- 24897458
TI  - Transitive responding in animals and humans: Exaptation rather than adaptation?
AB  - In order to survive and reproduce, individual animals need to navigate through a
      multidimensional utility landscape in a near-optimal way. There is little doubt
      that the behaviourally more advanced species can bring cognitive competencies to
      bear on this difficult task. Among the cognitive abilities that are helpful in
      this context is transitive inference. This is typically the competency to derive
      the conclusion B>D from the premises A>B, B>C, C>D and D>E that imply the series
      A>B>C>D>E. In transitive inference tests used with humans, the letters stand for
      verbal items and the inequality symbols stand for a relational expression. To
      investigate analogous competencies in non-human animals a non-verbal form of the
      task is used. The premise pairs are converted into a multiple instrumental
      discrimination task A+B-, B+C-, C+D- and D+E-, where the letters stand for non
      verbal stimuli and the plus and minus symbols indicate that choices of the
      corresponding stimuli either lead to a reward or to a penalty. When these
      training pairs are adequately discriminated, transitive responding is tested with
      intermittent presentations of the novel pair B?D?, where the circles indicate
      that responses to the stimuli are not reinforced. Using variants of this basic
      conditioning task it has been shown that pigeons, rats, squirrel-monkeys,
      macaques, chimpanzees, young children, older children and adult humans commonly
      reveal transitive preferences for B over D. Several theories have been proposed
      to explain this transitive behaviour. The evidence supporting these various
      models is reviewed. It is shown that the learning of the premises normally brings
      about a choice and reinforcement biasing and balancing process that can account
      for transitive responding. It is argued that a very simple algebraic learning
      model can satisfactorily simulate many of the results obtained in transitivity
      experiments, including some produced by human subjects who in principle, could
      have been applying rational logical rules. It is demonstrated that a value
      transfer mechanism also assumed to explain transitive responding, is in fact, a
      real phenomenon based on classical conditioning. However, it is argued that it
      mostly plays a minor role in transitive responding. It is shown that the
      algebraic learning model can be easily converted into a neural network model
      exhibiting an equivalent performance. The model can also be modified to cope with
      the surprising finding that a proportion of human individuals and a few animals
      subjects learn to discriminate the premise pairs, but nevertheless fail to
      respond transitively to the conclusion pair. This modification can simulate the
      results of experiments using non-linear, in particular circular, relational
      structures. The evolution of transitive responding is considered within the
      framework of ecosocial demands and neurobiological constraints. It is concluded
      that, in agreement with a preadaptation (exaptation) evolutionary origin, it
      seems to involve little beyond the capacity to learn multiple stimulus
      discriminations. 

PMID- 24897459
TI  - Allospecific vocal learning by Grey parrots (Psittacus erithacus): A failure of
      videotaped instruction under certain conditions.
AB  - Grey parrots (Psittacus erithacus) do not acquire referential English labels when
      tutored with videotapes in social isolation (Pepperberg, I.M., 1994. Auk 111, 300
      313) possibly because of (1) lack of social interaction to direct their attention
      appropriately or (2) absence of reward for an attempt at a targeted label. To
      test the first premise, two parrots watched videotapes with trainers who directed
      the birds' attention to the video monitor. Vocal praise rewarded attempts at a
      targeted label. To test the second premise, subjects watched videotapes in social
      isolation with a reward system that, in the absence of social interaction, could
      furnish the appropriate item after an attempt at the label. Subjects also
      received live interactive tutoring on a different set of object labels. Birds
      learned referential labels from live interactive tutors but not from videotapes.
      Specific aspects of live tutoring appear critical for the acquisition of
      referential English labels. 

PMID- 24897460
TI  - Social stimuli and social rewards in primate learning and cognition.
AB  - Many studies have suggested that non-human primates have good individual
      recognition abilities, that social stimuli can serve as discriminative stimuli in
      learning tests and that visual access to social objects or events can be a
      reinforcer for operant behaviour. Intensified research efforts comparing the
      effectiveness of social and non-social stimuli and rewards across a range of
      learning and other cognitive tasks would help clarify the extent to which monkeys
      and apes might be specially predisposed to process information in the social
      domain. In addition to identity, social interactions and relationships constitute
      raw material to be mentally represented and processed. Some studies have
      addressed the individual and evolutionary origins of mechanisms underlying the
      ability to attribute mental states and intentions to others, for example by
      looking at the understanding of another's gaze, imitation and the development of
      tactical deception. The results of some of this research suggest that only some
      species might be capable of higher-order attribution. Further progress in the
      study of primate social cognition will require continuing refinement of methods
      and the development of new techniques to compare primates as behaviourists and
      mentalists. 

PMID- 24897461
TI  - Interspecies object exchange: Bartering in apes?
AB  - Of 114 chimpanzees, 55 exchanged non-edible items for food items, indicating a
      proportion significantly greater than chance. In addition, those animals which
      did exchange were more likely to when encouraged by human solicitation. These
      behaviors suggest a social significance beyond simple behavioral economics in
      processing information about giving and getting. Further, these and several
      observed manipulations of reward-getting suggest that chimpanzees may also have a
      limited understanding of the expression and manipulation of the relative values
      of certain items. The behavioral foundations of and theoretical implications for
      primate social cognition and economic psychology are discussed. 

PMID- 24897462
TI  - Primate causal understanding in the physical and psychological domains.
AB  - Evidence for primates' understanding of causality is presented and discussed.
      Understanding causality requires the organism to understand not just that two
      events are associated with one another in space and time, but also that there is
      some 'mediating force' that binds the two events to one another which may be used
      to predict or control those events (e.g. a physical force such as gravity or a
      psychological force such as an intention). In the physical domain, studies of
      tool use indicate that capuchin monkeys do not have a causal understanding of the
      functioning of tools in terms of the physical forces involved, but rather they
      learn to associate aspects of their own behavior with the results it produces.
      Apes show some possible signs of understanding the causal relations involved in
      tool use in the sense that they may employ various forms of foresight in
      approaching novel tasks, perhaps involving an understanding of physical forces
      although not to the extent of human children. In the psychological domain,
      nonhuman primates understand conspecifics as animate beings that generate their
      own behavior and, thus, they appreciate that to manipulate conspecifics
      communicative signals, and not physical activities, are required. However, there
      is very little evidence that nonhuman primates of any species understand others
      as psychological beings with intentions and other psychological states that
      mediate their behavioral interactions with the world-as human children begin to
      do sometime during their second year of life. More research, using a wider range
      of problem-solving situations, is needed if we are to become more precise in our
      understanding of how primates understand the causal structure of the world around
      them. 

PMID- 24897463
TI  - Young and juvenile chimpanzees' (Pan troglodytes) reactions to intentional versus
      accidental and inadvertent actions.
AB  - Chimpanzees were tested for their ability to discriminate between
      accidental/inadvertent and intentional actions with equivalent adverse
      consequences. Subjects were first trained to 'point' to human trainers in order
      to receive food rewards. In Experiment 1, six 5-year-old subjects were
      alternately presented with two unfamiliar human actors. In condition 1, each
      actor either started to hand a cup of juice to the trainer but then pulled it
      back and intentionally poured it onto the floor, or accidentally spilled it while
      handing it to the trainer. In condition 2, the actors either accidentally spilled
      it as above, or aggressively threw the juice onto the floor. The subjects were
      then presented with both actors and were allowed to choose between them. In
      Experiment 2, seven 6-7-year-old chimpanzees were confronted with unfamiliar
      actors who either (a) intentionally withheld and consumed food intended for the
      subjects, (b) attempted to hand the intended food to the subjects but were
      victimized by a third party who consumed the food, or (c) always succeeded in
      delivering the food to the subjects. In general, the subjects showed little
      evidence of using the accidental/inadvertent versus intentional distinction in
      their choices between the actors, although they did display some evidence of
      favoring the actor involved in the most passive role in both conditions in
      Experiment 1. 

PMID- 24897464
TI  - The highs and lows of group homogeneity.
AB  - Two experiments yielded further evidence for the ingroup homogeneity effect
      (Kelly, C., 1989. Political identity and perceived intragroup homogeneity. Br. J.
      Soc. Psychol. 28, 239-250; Simon, B., 1992. The perception of ingroup and
      outgroup homogeneity: reintroducing the intergroup context. In: Stroebe, W.,
      Hewstone, M. (Eds.), Eur. Rev. Soc. Psychol. Vol. 3. Wiley, Chichester; Simon,
      B., Brown, R., 1987. Perceived intragroup homogeneity in minority-majority
      contexts. J. Personal. Soc. Psychol. 12, 463-468.). In the first experiment, with
      the aim of investigating the effect of the context of judgment, we asked
      psychology students to judge the variability of psychologists or of social
      workers (one-group conditions) or to judge both groups (two-group condition) on
      dimensions typical of psychologists and on dimensions typical of social workers.
      As predicted, whereas an ingroup homogeneity effect was found for the dimensions
      typical of the ingroup in the two-group condition, no asymmetry in perception of
      group variability emerged in the one-group conditions. In the second experiment,
      we examined the effect of ingroup identification in an explicit intergroup
      situation. In line with predictions, high identifiers perceived greater
      homogeneity in the ingroup than in the outgroup. In contrast, low identifiers
      displayed the opposite tendency. The impact of context and social identification
      on group entitativity is considered in its cognitive and motivational aspects. 

PMID- 24897465
TI  - Self-awareness and the evolution of social intelligence.
AB  - The use of one's own experience as a model to make inferences about the
      experiences of others is theorized to be the means by which a variety of
      introspectively based social strategies developed for both competing and
      cooperating with one another (e.g. gratitude, grudging, sympathy, empathy,
      deception, pretending and sorrow). The proposition that this ability is a
      byproduct of self-awareness is developed in some detail and the predictions which
      follow from this model of social intelligence are considered in light of the
      evidence. 

PMID- 24897466
TI  - [Experiences, perceptions and self-management of gestational diabetes in a group
      of overweight multiparous women].
AB  - Gestational diabetes mellitus (GDM) is a public health problem in Mexico and diet
      therapy is the main form of treatment. Self-management abilities are required to
      control the disease. Five women with GDM were studied to assess GDM risk
      perception and experiences related with self-management practices.
      Sociodemographic data were obtained and in-depth interviews were conducted and
      subsequently analyzed using Atlas ti V.5 software. The results revealed that
      women were conscious regarding the role of diet and physical activity in
      improving GDM control, and about the perinatal risks associated with the disease.
      Adherence to diet recommendations was partial, but gradual and positive lifestyle
      changes were observed. Emotionally, perception about having GDM was a key factor
      with respect to adhering to the diet. In conclusion, the medical and dietary
      treatment influences the cultural food behavior of women with GDM. Health
      professionals should consider sociocultural determinants when designing and
      implementing treatment strategies. 

PMID- 24897467
TI  - [Missed opportunity for timely diagnosis of diabetes mellitus in Afrodescendant
      communities in the southwest of the state of Bahia, Brazil].
AB  - The scope of this study was to estimate the prevalence and associated factors of
      missed opportunities for timely diagnosis of diabetes mellitus in Afrodescendant
      communities in Vitoria da Conquista in the state of Bahia. It involved a
      population-based cross-sectional study based on a probability sample (n=797),
      where 548 individuals were eligible for analysis considering the risk criteria:
      age of 45 years old and above, increased Body Mass Index and hypertension. The
      prevalence of diabetes mellitus was estimated at 42.6%. Logistic regression
      indicated the following statistically associated factors: self-assessed good/very
      good health conditions; not measuring blood pressure and not consulting with a
      physician in the past twelve months; and poor access to health services. The high
      prevalence was associated with factors related to low utilization and poor access
      to health services. Actions for the diagnosis and prevention of diabetes should
      prioritize populations at risk, including better education and training of family
      health care teams, and improvement of attendance at health care units. Enhanced
      integration between primary and secondary health care actions can positively
      impact early diagnosis, treatment and reduction of potential complications
      associated with diabetes in this population. 

PMID- 24897468
TI  - [Estimate of cost for diabetic foot treatment; how to prevent it and save funds].
AB  - In this work the cost of hospital treatment for diabetic foot wounds was
      estimated and the literature regarding prophylaxis for these lesions was
      examined. For this purpose, the records of all patients with diabetic foot
      symptoms submitted to surgical treatment over a period of 16 months in a public
      hospital were reviewed. There were 44 admissions with an average hospitalization
      period of 11.93 days, (+/- 6.34), 61 surgical procedures, with amputations in 65%
      of the cases. An average cost of R$ 4,367.05 (+/- 9249.01) and a total cost of R$
      192,150.40 was calculated for the hospital treatment involved. Treatment of
      diabetic foot symptoms had a high cost and required amputation in the majority of
      cases. A review of the literature revealed many possible models to be adopted for
      action in the prophylaxis of wounds associated with the diabetic foot, which can
      avoid amputations and save funds. 

PMID- 24897469
TI  - [Rational use of medicines by individuals with diabetes mellitus and arterial
      hypertension in the municipality of Rio de Janeiro, Brazil].
AB  - This study focuses on the rational use of medicines (RUM) by hypertensive and/or
      diabetic patients treated in primary health care units in the city of Rio de
      Janeiro. It involves a cross-sectional study conducted between January and
      February 2010. Indicators were created considering the following aspects:
      adherence to prescribed medicine, self-medication and how patients store
      medicines within their households. Univariate and multivariate data analysis was
      performed. Of the 547 patients studied, 77.5% reported that they usually take the
      entire course of medicines and 80.3% reported that they tend not to forget to
      take them. Almost all respondents reported that they only take medications
      prescribed by authorized health professionals. Half of the patients had no
      expired medicines or damaged medicine packages in the home. Statistical tests
      revealed that RUM is higher among hypertensive individuals who are married and
      working, who mention receiving medical guidance about diet and physical exercise,
      and who have not missed any scheduled medical appointments at the primary health
      care unit within the 6 months before this research was conducted. The findings
      emphasize the importance of primary health care in promoting the rational use of
      medicines. 

PMID- 24897470
TI  - [Accuracy of registration data for patients with arterial hypertension and
      diabetes mellitus recorded in the Hiperdia system in a state in the northeast of
      Brazil].
AB  - The scope of this study was to evaluate the accuracy of the data recorded in the
      Hiperdia system assessed by geographical area, type of field and information
      consistency between related variables. It involved an observational, descriptive
      and cross-sectional investigation. The sample of 287 registration forms was
      randomly and proportionally obtained from the five health regions. Variables
      relating to blocks of registration and attendance data were selected using the
      percentage of inaccuracy as an indicator and classification was then made using
      the Romero and Cunha score (2007). The percentages between the health macro
      regions was compared using the chi-square test and the completion consistency was
      assessed using the Kappa coefficient. Of the 32 variables studied, 68.7% revealed
      good to excellent accuracy. In 62.5% of the variables, the accuracy of the data
      of the 2nd health macroregion was marked. The percentages of inaccuracy of
      mandatory data were higher than those for non-mandatory data. Although most of
      the variables revealed good usage conditions, greater involvement of managers and
      health professionals in the information production process is required in order
      to generate more accurate and reliable data. 

PMID- 24897471
TI  - [Arterial hypertension among adolescents in Rio de Janeiro: prevalence and
      association with physical activity and obesity].
AB  - The scope of this study was to identify the prevalence of systemic arterial
      hypertension among adolescent students (aged 17-19 years) in the third and final
      year of high school in state schools in the municipality of Rio de Janeiro, and
      to investigate associations between systemic arterial hypertension and obesity
      and physical activity levels. Data on arterial pressure, body mass index and
      physical activity were gathered. The analysis included 854 individuals.
      Descriptive statistical analysis was applied to the sample, along with a Poisson
      regression model to determine the impact of the variables on the prevalence of
      systemic arterial hypertension. The prevalence of systemic arterial hypertension
      was 19.4%. Male sex, overweight and obesity presented significant positive
      associations with systemic arterial hypertension (p < 0.05), while physical
      activity was not shown to be significantly associated with systemic arterial
      hypertension (p > 0.05). The nature of these relationships should be interpreted
      in the light of reflection and not of passive labeling based on hegemonic
      concepts. 

PMID- 24897472
TI  - [Analysis of the relation between the spatial distribution of morbidities due to
      obesity and hypertension for the State of Sao Paulo, Brazil, from 2000 to 2010].
AB  - The increased prevalence of obesity in many countries in the last decade has
      resulted in increased morbidity and mortality from hypertension and associated
      complications. The objective of this work is to analyze the spatial distribution
      of obesity and hypertension in the state of Sao Paulo in the period from 2000 to
      2010, based on hospital records and admissions from the Hospital Information
      System of the Unified Health System (HIS - SUS). Coefficients were used for the
      prevalence of the disease in each municipality averaged out by the empirical
      Bayesian method, enabling visualization of the spatial pattern of these
      morbidities in the state. The spatial dependence of these standards was assessed
      by checking the autocorrelation between the indicators by calculating Moran's
      Index of Spatial Autocorrelation. Furthermore, the positive correlation (Pearson)
      between obesity and hypertension was investigated. Data and maps showed clusters
      of 87 municipalities where there are higher and lower prevalence of hypertension
      and obesity in the location with marked autocorrelation between neighboring
      municipalities. The Pearson correlation coefficient found for these
      municipalities was 0.404 and suggests an association between the morbidities. The
      spatial analysis techniques proved useful for planning public health actions. 

PMID- 24897473
TI  - [The other side of obesity: reflections for a sociocultural approach].
AB  - This paper addresses the proposition that even though there appears to be
      unanimity on the biomedical diagnosis of obesity, it is insufficient or not
      precise enough, since it is necessary to know more about the consequences of
      different lifestyles in ways of eating and the impact of lifestyles on the health
      of the population. Therefore, the paper reflects on how the biomedical ideation
      of obesity contributes to make body weight and food into what from a rather
      reductionist and controversial approach is defined as a "social problem." Lastly,
      the standardization of international strategies against obesity is considered,
      linked to its classification as a global epidemic, in order to reflect on the
      effects of dealing with a limited view of culture and food. The ideas articulated
      in this work are part of the theoretical problematization phase of the topic,
      prior to the implementation of the research project entitled a socio
      anthropological approach to childhood obesity in three case studies: Spain,
      Mexico and Cuba. 

PMID- 24897474
TI  - [Cardiovascular risk factors on the Framingham Risk Score among hypertensive
      patients attended by family health teams].
AB  - The Framingham Risk Score (FRS) is used to stratify cardiovascular risk. This
      study sought to identify the prevalence of risk factors used in the FRS and the
      use of drugs that reduce cardiovascular risk among hypertensive patients attended
      by the Family Health Strategy (FHS). It is cross-sectional study, which evaluated
      a random sample of hypertensive patients in the FHS in northern Minas Gerais.
      Data were collected through interviews and from medical records. 505 hypertensive
      patients were evaluated in 9 municipalities of the region, with a predominance of
      women; 325 (64.4%), mean age of 66.4 years. In 90% of hypertensive patients there
      was at least one associated risk factor. The grouping of three or more factors
      occurred in 79 (15.7%) patients. Dyslipidemia was found in 188 (37.2%), diabetes
      in 101 (20%) and smoking in 36 (7.1%). The use of anti-hypertensive drugs was
      observed in 481 (95.2%) patients. The use of other cardioprotective drugs was
      higher among patients with 3 or more risk factors: 45.6% used antiplatelet and
      27.8% used lipid-lowering drugs. The prevalence of risk factors from the FRS in
      the population studied was quite high and the use of cardioprotective drugs was
      seen to be restricted. Strategies to increase the use of FRS may improve the
      management of hypertension in the FHS. 

PMID- 24897475
TI  - [Abdominal obesity: a critical review of the measurement techniques and cutoff
      points of anthropometric indicators adopted in Brazil].
AB  - The scope of this article is to assess the suitability of the measurement
      techniques and the cutoff points of anthropometric indicators of abdominal
      obesity adopted in Brazil, and summarize the results. This involves a review of
      the literature published from 1990 to 2010 and indexed in the MEDLINE, LILACS and
      SciELO databases. The inclusion criteria for articles were: original research
      articles with abstracts available of experimental or observational design
      conducted in Brazil, in English, Spanish or Portuguese; articles about assessment
      of abdominal obesity with the use of anthropometric indicators of central
      distribution. Eighteen articles characterized according to author and publication
      year, study site, study type, sample size, age, sex, anthropometric indicators,
      measurement techniques, cutoff points and main results were selected. A
      divergence was found between studies in terms of standardized technical
      procedures and cutoff points. The results of this review recommend the
      standardized use of the validated measurement techniques and cutoff points in
      order to facilitate comparison of the results of the epidemiological studies into
      abdominal obesity and their adequate use in clinical practice. 

PMID- 24897476
TI  - [Obesity in adolescents and public policies on nutrition].
AB  - In recent years, obesity has become a major public health problem and its
      prevalence is increasing at an alarming pace. Moreover, this problem has affected
      children and adolescents in marked fashion. Considering this situation, public
      policies on nutrition were created as strategies to attempt to combat/control the
      high Brazilian obesity indices. The scope of this study was to conduct a
      historical analysis of the advances in Brazilian public policies related to
      nutrition/food and the practice of physical exercise to control obesity among
      adolescents. In this respect, a review was conducted of the literature in the
      PubMed and SciELO electronic databases that addresses Brazilian public policies
      on nutrition in the control of obesity. Official documents of the Ministry of
      Health, scientific articles, journals and the recommendations of the World Health
      Organization were also used in the research. The results revealed that public
      policies on nutrition practiced in Brazil have been implemented in an incipient
      manner when directed at adolescents with respect to the obesity factor.
      Therefore, a broader vision seeking policies that attempt to control obesity in
      adolescents is of paramount importance. 

PMID- 24897477
TI  - Obesity and periodontitis: systematic review and meta-analysis.
AB  - The scope of this study was to conduct a systematic review of the studies on the
      association between obesity and periodontitis. The methods applied included a
      literature search strategy and selection of studies using inclusion and exclusion
      in accordance with the criteria for characteristics of the studies and meta
      analysis. The research was conducted in the PubMed, Embase and Lilacs databases
      through 2010. Selected papers were on studies on humans investigating whether or
      not obesity is a risk factor for periodontitis. Of the 822 studies identified, 31
      studies met the inclusion criteria and were included in this meta-analysis. The
      risk of periodontitis was associated with obesity (or had a tendency for this) in
      25 studies, though it was not associated in 6 studies. The meta-analysis showed a
      significant association with obesity and periodontitis (OR = 1.30 [95% Confidence
      Interval (CI), 1.25 - 1.35]) and with mean Body Mass Index (BMI) and periodontal
      disease (mean difference = 2.75). Obesity was associated with periodontitis,
      however the risk factors that aggravate these diseases should be better clarified
      to elucidate the direction of this association. Working with paired samples and
      avoiding confusion factors may contribute to homogeneity between the studies. 

PMID- 24897478
TI  - [The role of religion in the promotion of health, in the prevention of violence
      and in the rehabilitation of individuals involved in criminal activity:
      literature review].
AB  - This is a review of the literature on the role of religion in the promotion of
      health, the prevention of violence and the rehabilitation of individuals involved
      in criminal activities. Research was conducted in the Medline through PubMed,
      Lilacs, Scopus, Social Index with full text, Sociological abstracts and Social
      services abstracts databases. Twenty-nine essays in Portuguese, English and
      Spanish were selected and analyzed between 1990 and 2011. The results indicate
      the function of the religious group and the role of religion in the
      rehabilitation of individuals, the prevention of criminal involvement, corrective
      orientations and in social iniquity environments. A debate is presented on the
      main themes revealed, highlighting the multiplicity of religious roles, their
      influence over prisoners, as a social control and support base and its influence
      on mental health promotion and quality of life. The relation between religion and
      the public sphere is discussed, emphasizing the role of religious groups and the
      fragility of the State in providing basic public policies. Despite revealing the
      successful role of religion in violence prevention and in rehabilitation, some
      studies question this relation and highlight the conflicts between the concepts
      employed and the final results. 

PMID- 24897479
TI  - [Body image of adolescents in rural cities].
AB  - The scope of this article is to evaluate the body image of adolescents from rural
      cities and its relationship with nutritional status, sex and the adolescent
      phase. Adolescents of both sexes participated in the cross-sectional study. Body
      image was evaluated through the Body Shape Questionnaire (BSQ) and the Figure
      Rating Scale (FRS) for adolescents. Weight and height were measured for the
      evaluation of body mass index (BMI). Stages of adolescence were classified by
      age. Descriptive and inferential statistical analyses were conducted. Four
      hundred and forty-five adolescents (190 boys and 255 girls), with a mean age of
      16.44 comprised the sample. Higher risk of body dissatisfaction was found among
      overweight and obese participants (BSQ: OR = 3.359 p < 0.001; ESA: OR = 1.572 p =
      0.387) and the female sex (BSQ: OR = 3.694 p < 0.001; ESA: OR = 0.922, p =
      0.840). Participants from the intermediary and final stages of adolescence
      revealed a lesser risk of dissatisfaction compared to those from the initial
      phase. Body dissatisfaction was related to overweight and obesity, to the female
      sex and to the initial period of adolescence. Intervention research is required
      to control the factors that influence excessive adolescent body dissatisfaction. 

PMID- 24897481
TI  - [Survival for ten years and prognostic factors for women with breast cancer in
      Joinville in the State of Santa Catarina, Brazil].
AB  - Breast cancer has the highest incidence among women, and reduces survival among
      female sufferers. This article aims to evaluate the survival and its prognostic
      factors in women with breast cancer, treated by public sector, in Joinville,
      Santa Catarina, Brazil. Retrospective cohort study nested in a case-control. The
      data has been obtained by a questionnaire, by the review of records and death
      certifications. In the analysis of survival it has been applied the Kaplan
      Meier's statistical method and the Cox's method. 170 women have been evaluated.
      The survival in ten years was 83.1% (95% CI 74.1 to 89.3%), and 21 (12.4%) deaths
      were identified at the time period. The probability of being alive was smaller
      for those in advanced stages of cancer; the risk of death was higher among those
      who had another kinds of cancer associated, and among those unsatisfied with
      life. The death's ratio was 17.1 times bigger among women diagnosed in advanced
      stages. The variable staging presented higher association with the survival in
      evaluated women. Detecting the disease early minimizes the mortality by breast
      cancer. 

PMID- 24897480
TI  - [Estimates of life expectancy for individuals with chronic spinal diseases in
      Brazil].
AB  - Chronic spinal diseases, including deformities and muscular pain, are significant
      causes of morbidity among adults and the elderly. The scope of this study is to
      assess the life expectancy of Brazilians with chronic spinal diseases by sex and
      age between 2003 and 2008. The Sullivan method was used, combining the
      mortality/actuarial table with the prevalence of chronic spinal diseases. The
      mortality/actuarial tables published by the Brazilian Institute of Geography and
      Statistics (IBGE) were used and the prevalence of chronic spinal diseases was
      taken from the Brazilian Household Sample Survey (PNAD) for the years under
      scrutiny. The main results indicate that a man born in Brazil in 2008 could
      expect to live for 69.1 years, of which 15% with chronic spinal diseases.
      However, women born in the same year had a life expectancy of 76.7 years and
      could expect to live a fifth of their lives with chronic spinal diseases. Over
      the period under analysis, concurrently with gains in life expectancy, there was
      an increase in healthy life expectancy, or length of life lived without chronic
      spinal diseases, both in absolute and relative terms. 

PMID- 24897482
TI  - [Antidepressants: use, adherence and awareness among medical students].
AB  - This study assessed the degree of adherence and drug-related awareness and
      opinions regarding the importance of guidance with respect to treatment among
      medical students who use antidepressants. It is a cross-sectional descriptive
      study, carried out in a public Medical School in the state of Sao Paulo, Brazil.
      Of the 289 students interviewed, 33 (11.4%) use or had already used
      antidepressants, with fluoxetine being the most prescribed. The nurse was not
      cited as being responsible for guidance on the antidepressant. Although most
      students had received guidance on antidepressants, they did not heed guidance and
      still had doubts regarding their use. There was a statistically significant
      association regarding the consumption of other drugs in addition to
      antidepressants and the existence of side effects, as well as regarding an
      increase of the dosage without medical consultation and the existence of such
      side effects. Actions are necessary to acknowledge the importance of the teaching
      of psychopharmacology in the training of the medical professional and for greater
      harmony between theory and practice. 

PMID- 24897483
TI  - [Health survey in Quilombola communities (descendants of Afro-Brazilian slaves
      who escaped from slave plantations that existed in Brazil until abolition in
      1888) in Vitoria da Conquista in the state of Bahia (COMQUISTA Project), Brazil:
      methodological aspects and descriptive analysis].
AB  - The scope of this article was to present the methodology, preliminary descriptive
      results and the reliability of the instruments used in the COMQUISTA Project. It
      involved a cross-sectional study with adults (>18 years) and children (up to 5
      years old) of Quilombola communities in Vitoria da Conquista, Bahia. Data
      collection consisted of individual and household interviews, anthropometric and
      blood pressure measurements. A semi-structured questionnaire adapted from the
      Brazilian National Health Survey (PNS) was used and the interviews were conducted
      using handheld computers. 397 housing units were visited and 797 adults and 130
      children were interviewed. The demographic profile of the Quilombolas was similar
      to the Brazilian population with respect to sex and age, however, they had
      precarious access to basic sanitation and a low socioeconomic status. The
      analysis of reliability revealed the adequacy of strategies adopted for quality
      assurance and control in the study. The methodology used was considered adequate
      to achieve the objectives and can be used in other populations. The results
      indicate the need for implementing strategies to improve the quality of life and
      reduce the degree of vulnerability of the Quilombolas. 

PMID- 24897484
TI  - [Adult tooth loss profile in accordance with social capital and demographic and
      socioeconomic characteristics].
AB  - Demographic and socioeconomic conditions play an important role in tooth loss in
      the population, however, there is little scientific evidence regarding the
      influence of social capital on this outcome. The scope of this study was to
      describe the tooth loss profile of adults aged 35-44, who are residents of the
      surrounding area of the city of Belo Horizonte in the state of Minas Gerais. This
      cross-sectional exploratory study comprised a sample of 1,013 adults. The
      dependent variable was tooth loss. Exploratory variables were social capital,
      demographic and socioeconomic characteristics. The Chi-squared Automatic
      Interaction Detector (CHAID) was used to map the adult tooth loss profile which
      was explained by low levels of social capital (47.0%; p < 0.001), more elderly
      adults (60.2%; p < 0.001), and low education levels (66.3%; p = 0.022). In the
      high social capital group, age was the determinant factor of tooth loss,
      irrespective of educational level or per capita income. The conclusion, at the
      individual level, is that social capital as well as demographic and socio
      economic characteristics explained the adult tooth loss profile. Individual
      social capital may have attenuated the negative influence of socioeconomic
      factors in the population under scrutiny. 

PMID- 24897485
TI  - [An overview of the variations surrounding the concept of medicalization between
      1950 and 2010].
AB  - This article examines the pertinence of the concept of medicalization for socio
      cultural analysis. The study is based on the criticism which emerged in the
      international literature between 2000 and 2010. The criticism stressed the
      excessive generality of the expression that encompasses different situations and
      thereby loses its analytical precision. The main meanings of the term
      medicalization are examined, namely 1) the major strategies of hygienization of
      the population; 2) the transformation of behavior considered deviant into
      disorders; 3) control strategies and the medical imperative; 4) the participation
      of non-medical actors. Based on the different meanings of the notion of
      medicalization, the transient nature of the concept needs to be stressed, i.e.
      the need to specify the different meanings attributed to the notion depending on
      the different contexts in which it is used. If this is not done, the concept will
      lose its theoretical accuracy and will possibly no longer be useful for social
      analysis. 

PMID- 24897486
TI  - [Intergenerational social mobility and health in Brazil: analyzing the "Social
      Dimensions of Inequalilies Survey (PDSD)," 2008].
AB  - Although most studies consider health to be the result of social and economic
      insertion of the individuals, health may be considered a determining factor of
      the social opportunities achieved, especially with respect to chances of social
      mobility. The scope of this article is to understand the magnitude of the
      concurrent associations that sociodemographic, health and quality of life
      conditions (SF-36) exercise on chances of intergenerational social mobility on a
      probability sample of Brazilian homes in 2008. Social mobility was determined by
      the transition between occupational groups, which were defined using the
      Ganzeboom scale. Sociodemographic, health and quality of life features were
      associated with upward social mobility through logistic regression. A high level
      of schooling was the main determinant of chances of intergenerational social
      mobility. Women and youngsters ascended more intergenerationally. A positive
      association was observed between self assessment of health, physical health
      scores and upward mobility. Social mobility has become established as a
      multideterminate event. Physical health and perceived health were capable of
      influencing social transitions. 

PMID- 24897487
TI  - Association between ongoing pain intensity, health-related quality of life,
      disability and quality of sleep in elderly people with total knee arthroplasty.
AB  - The scope of this paper was to study the relationship between pain intensity,
      health-related quality of life, disability, sleep quality and demographic data in
      elderly people with total knee arthroplasty (TKA). 24 subjects who had been
      subjected to TKA the previous month (4 females; 66 +/- 9years) and 21 comparable
      controls (8 male; 70 +/- 9years) participated in the study. Intensity of pain,
      and highest and lowest pain intensity experienced in the preceding week were
      collected. The Western Ontario and McMaster Universities index function, quality
      of life (Medical Outcomes Study Short Form 36), and Pittsburgh Sleep Quality
      Index were assessed. Age, gender, weight, height, body mass index were also
      collected. Individuals with TKA presented worse physical function (P < 0.01),
      social role (P = 0.01), physical performance (P < 0.01), pain (P = 0.04),
      disability (P = 0.04) and sleep quality (P = 0.03) than the controls. Higher
      intensity of pain was associated with lower physical function, social role,
      mental health, vitality and general health, and with higher disability and sleep
      quality. Disability and sleep quality were negatively associated with several
      quality of life domains. The associations between the intensity of pain,
      disability, quality of life and sleep reveal the multidimensional experience of
      TKA. 

PMID- 24897488
TI  - [The evolution of mortality by homicide in the State of Bahia in the period from
      1996 to 2010].
AB  - An ecological study was conducted, the objective of which was to describe the
      evolution of homicide rates for residents of the State of Bahia, Brazil, and its
      nine health macroregions (MRS) in the period from 1996 to 2010. Crude and
      adjusted data from the Mortality Information System (SIM) and X85-Y09 codes of
      the Tenth International Statistical Classification of Diseases and Related Health
      Problems (ICD-10) were analyzed. The number, proportion and homicide mortality
      rates (TMH) were analyzed. considering the characteristics of the victim and the
      event. The results revealed a profile of predominantly male mortality, Afro
      Brazilian race/ethnicity with little education. The public highways were the main
      location of occurrence of deaths. There was an increase in TMH in all age groups,
      though the highest rates were observed in the population of 15 to 39 years of
      age. The TMH age-standardized rates were higher in the Far South, East, North and
      South. The conclusion reached was that the killings can be addressed from the
      loation/regional realities through strategic and planning of intersectoral
      actions that take into account the socioeconomic and cultural characteristics. 

PMID- 24897489
TI  - [Translation, adaptation and validation of the Fantastic Lifestyle Assessment
      questionnaire with students in higher education].
AB  - The scope of this study was to make the translation, cultural adaptation and
      validation of the Fantastic Lifestyle Assessment questionnaire in a group of
      students in higher education in Portugal. The process of translation and
      validation consisted of translation, back translation, expert committee review,
      pre-testing and testing of the psychometric properties. The final version adapted
      with 30 questions was applied to a sample of 707 university students. The results
      showed that the instrument demonstrated good overall internal consistency for an
      instrument used to measure a latent variable. When the items were grouped into
      domains, it was found that they all contributed equally to the stability of the
      instrument. The reproducibility assessed by intraclass correlation was high.
      Construct validity tested by the classification capacity of the instrument in
      four, three and two categories was 67.6%, 67.6% and 100%, with a Kappa index of
      0.55, 0.55 and 1.00, respectively. The concurrent validity was also evaluated by
      correlating it with "My Lifestyle," namely another instrument measuring the same
      construct. The conclusion was that the Fantastic Lifestyle Assessment, is a
      reliable and valid instrument for lifestyle assessment in young adults. 

PMID- 24897490
TI  - [The limits of collective action in municipal health councils].
AB  - This article addresses the collective actions of participation in the municipal
      health councils. The underlying research sought to establish the performance of
      the councilors in the municipal health councils in the Metropolitan Region of
      Belem in the State of Para. A survey of documents for the 2005-2010 period,
      structured interviews and observations with counselors in sessions of meetings of
      the boards of three counties were analyzed. An indicator of three levels of
      participation centered on the legal functions of the health councils and based on
      the theory of social groups as its analytical principle was constructed. The
      results indicate that the activities of the councils are marked by the co-option
      of councilors and the definition of deliberative agendas on the part of
      representatives of management, in which individual interests predominate over the
      collective interests of the councilors in the deliberations. The conclusion is
      that such behavior is contrary to the principles of the Unified Health System -
      SUS and weakens the social image of the councils, in addition to opening up a new
      analytical perspective. 

PMID- 24897491
TI  - [Brazilian bibliographical output on public oral health in public health and
      dentistry journals].
AB  - The scope of this paper is to describe characteristics of the scientific output
      in the area of public oral health in journals on public health and dentistry
      nationwide. The Scopus database of abstracts and quotations was used and eight
      journals in public health, as well as ten in dentistry, dating from 1947 to 2011
      were selected. A research strategy using key words regarding oral health in
      public health and key words about public health in dentistry was used to locate
      articles. The themes selected were based on the frequency of key words. Of the
      total number of articles, 4.7% (n = 642) were found in oral health journals and
      6.8% (n = 245) in public health journals. Among the authors who published most,
      only 12% published in both fields. There was a percentile growth of public oral
      health publications in dentistry journals, though not in public health journals.
      In dentistry, only studies indexed as being on the topic of epidemiology showed
      an increase. In the area of public health, planning was predominant in all the
      phases studied. Research to evaluate the impact of research and postgraduate
      policies in scientific production is required. 

PMID- 24897492
TI  - [The use of metaphors to express toothache: a study in the field of the
      anthropology of health].
AB  - This research was conducted with patients who sought emergency care at a
      Comprehensive Primary Care Clinic (CIAP IV) at the Dental School of Minas Gerais
      Federal University and at the Dental Center of a medium-sized city in the state
      of Minas Gerais. The scope of this article is to identify how the social
      representations of this issue are generated through the metaphors used by
      patients to express toothache. A total of 35 individuals of both genders who
      sought emergency care for toothache participated in the study. Content theme
      analysis was used. Social representations of toothache are generated as people
      resort to their life experiences to find words to express the problem. Prior
      sensations and feelings, and even imaginary situations, generate metaphors to
      attempt to explain the suffering. Toothache is often compared with the worst
      feelings ever experienced by individuals. Toothache represents great suffering
      for people seeking emergency dental care. This fact may help to develop further
      public oral health policies, bearing in mind that a socially deprived population
      is more often afflicted by toothache. 

PMID- 24897493
TI  - [Association between social capital and oral health conditions and behavior].
AB  - The theory of social capital seeks to explain social inequality in health through
      the interaction of social, economic and environmental factors and has been
      associated with many health problems, though there is still little research in
      the area of oral health. The scope of this study was to evaluate the association
      between social capital and socio-demographic and behavioral factors related to
      oral health among schoolchildren aged from 15 to 19. A random sample of 1,417
      adolescents filled out a self-administered survey and the data were descriptively
      analyzed (simple frequencies, central tendency and variability measurement) and
      inferential statistics (Pearson's chi-square test). The results showed that the
      social capital which is more prevalent among adolescents was intermediate level,
      as well as between each of its dimensions, except for social action where the
      majority were classified as lower-leveled. Among the variables analyzed, social
      capital was statistically associated only with sex, with women being more likely
      to be classified under the 'low social capital' label. This area still needs
      considerable research to increase theoretical-conceptual and methodological
      maturity in order to better understand the social contexts that are essential for
      formulating effective public health policies. 

PMID- 24897494
TI  - [Perception of AIDS among health professionals who experienced the epidemic while
      caring for people with the disease in Florianopolis in the state of Santa
      Catarina, Brazil (1986-2006)].
AB  - The scope of this study is to ascertain how the health professionals of a
      Reference Hospital for Infectious diseases experienced the AIDS epidemic while
      caring for people with the disease between 1986 and 2006. It involved a
      qualitative study with a socio-historical approach that used oral history to
      collect data from twenty-three health professionals. The following categories
      emerged from the content analysis: a change in profile of the AIDS epidemic; the
      improvement of care for people with HIV/AIDS; and an improvement in working
      conditions. The health professionals who experienced the epidemic while caring
      for patients with the disease perceived how much public health policies on AIDS,
      with advances and research, led to the consolidation of many laws. It also led to
      the coordination of health programs aimed at the improvement of services,
      assistance to people with the disease and ensuring a safer and less tiring work
      environment. 

PMID- 24897495
TI  - [Social representation of sexual violence and its relationship with the adherence
      to the chemoprophylaxis protocol of HIV in young women and adolescents].
AB  - The scope of this study was to understand the social representations of sexual
      violence and its relationship with adherence to the chemoprophylaxis protocol of
      HIV in young women and adolescents. Qualitative research was conducted based on
      the theory of social representations through recorded interviews with 13 female
      subjects aged between 12 and 23. It was observed that the social representations
      about sexual violence exerted a considerable influence on adherence to
      chemoprophylaxis treatment in the group. The individuals surveyed elaborated
      images in which the concern caused to the family, discomfort caused by the
      effects of drugs, change of routine, fear of getting sick, being stigmatized,
      anxiety and anger, appeared as constant elements, which can lead to the
      abandonment of treatment. Considering the influence of these representations on
      treatment, there is a need for greater attention of the health services in
      relation to these possibilities, and for resources to ensure care based on these
      different needs. In addition to investing in research into new drugs, it is
      necessary to invest in qualitative research, providing input for more appropriate
      care for patients. 

PMID- 24897497
TI  - Temperature-dependent nonlinear phonon shifts in a supported MoS2 monolayer.
AB  - We report Raman spectra measurements on a MoS(2) monolayer supported on SiO(2) as
      a function of temperature. Unlike in previous studies, the positions of the two
      main Raman modes, E(2g)(1) and A(1g) exhibited nonlinear temperature dependence.
      Temperature dependence of phonon shifts and widths is explained by optical phonon
      decay process into two acoustic phonons. On the basis of Raman measurements,
      local temperature change under laser heating power at different global
      temperatures is derived. Obtained results contribute to our understanding of the
      thermal properties of two-dimensional atomic crystals and can help to solve the
      problem of heat dissipation, which is crucial for use in the next generation of
      nanoelectronic devices.

PMID- 24897498
TI  - Diet-induced obesity and insulin resistance spur tumor growth and cancer cachexia
      in rats bearing the Yoshida sarcoma.
AB  - Obesity and insulin resistance are associated with increased risk of cancer and
      cancer mortality. However, it is currently unknown whether they contribute to the
      development of cancer cachexia, a syndrome that contributes significantly to
      morbidity and mortality in individuals with cancer. The present experiment
      addresses the question of whether preexisting obesity and insulin resistance
      alter tumor growth and cancer cachexia symptoms in Yoshida sarcoma bearing male
      rats. Obesity and insulin resistance were induced through 5 weeks of high-fat
      (HF) diet feeding and insulin resistance was confirmed by intraperitoneal glucose
      tolerance testing. Chow-fed animals were used as a control group. Following the
      establishment of insulin resistance, HF- and chow-fed animals were implanted with
      fragments of the Yoshida sarcoma or received a sham surgery. Tumor growth rate
      was greater in HF-fed animals, resulting in larger tumors. In addition, cancer
      cachexia symptoms developed in HF-fed animals but not chow-fed animals during the
      18-day experiment. These results support a stimulatory effect of obesity and
      insulin resistance on tumor growth and cancer cachexia development in Yoshida
      sarcoma-bearing rats. Future research should investigate the relationship between
      obesity, insulin resistance, and cancer cachexia in human subjects. 

PMID- 24897499
TI  - Deep sequencing of cancer-related genes revealed GNAS mutations to be associated
      with intraductal papillary mucinous neoplasms and its main pancreatic duct
      dilation.
AB  - BACKGROUND: To clarify the genetic mutations associated with intraductal
      papillary mucinous neoplasms (IPMN) and IPMN-related pancreatic tumours, we
      conducted cancer-related gene profiling analyses using pure pancreatic juice and
      resected pancreatic tissues. METHODS: Pure pancreatic juice was collected from
      152 patients [nine with a normal pancreas, 22 with chronic pancreatitis (CP), 39
      with pancreatic ductal adenocarcinoma (PDAC), and 82 with IPMN], and resected
      tissues from the pancreas were collected from 48 patients (six IPMNs and 42
      PDACs). The extracted DNA was amplified by multiplexed polymerase chain reaction
      (PCR) targeting 46 cancer-related genes containing 739 mutational hotspots. The
      mutations were analysed using a semiconductor-based DNA sequencer. RESULTS: Among
      the 46 cancer-related genes, KRAS and GNAS mutations were most frequently
      detected in both PDAC and IPMN cases. In pure pancreatic juice, GNAS mutations
      were detected in 7.7% of PDAC cases and 41.5% of IPMN cases (p<0.001 vs. others).
      All PDAC cases with GNAS mutations (n = 3) were accompanied by IPMN. Multivariate
      analysis revealed that GNAS mutations in IPMN cases were associated with dilated
      main pancreatic ducts (MPD, p = 0.016), while no statistically independent
      associations with clinical variables were observed for KRAS mutations. In the
      resected pancreatic tissues, GNAS mutations were detected in 50% of PDAC cases
      concomitant with IPMN, 33.3% of PDAC cases derived from IPMN, and 66.7% of IPMN
      cases, while no GNAS mutations were detected in cases of PDAC without IPMN.
      CONCLUSIONS: The GNAS mutation was specifically found in the cases with IPMN and
      it was speculated that some PDACs might be influenced by the concomitant but
      separately-located IPMN in their pathogenic mechanism. Furthermore, the GNAS
      mutation was significantly associated with MPD dilatation in IPMN cases,
      suggesting its role in mucus hypersecretion.

PMID- 24897500
TI  - The CD200-CD200 receptor inhibitory axis controls arteriogenesis and local T
      lymphocyte influx.
AB  - The role of the CD200 ligand-CD200 receptor (CD200-CD200R) inhibitory axis is
      highly important in controlling myeloid cell function. Since the activation of
      myeloid cells is crucial in arteriogenesis, we hypothesized that disruption of
      the CD200-CD200R axis promotes arteriogenesis in a murine hindlimb ischemia
      model. Female Cd200-/- and wildtype (C57Bl/6J) mice underwent unilateral femoral
      artery ligation. Perfusion recovery was monitored over 7 days using Laser-Doppler
      analysis and was increased in Cd200-/- mice at day 3 and 7 after femoral artery
      ligation, compared to wildtype. Histology was performed on hindlimb muscles at
      baseline, day 3 and 7 to assess vessel geometry and number and inflammatory cell
      influx. Vessel geometry in non-ischemic muscles was larger, and vessel numbers in
      ischemic muscles were increased in Cd200-/- mice compared to wildtype.
      Furthermore, T lymphocyte influx was increased in Cd200-/- compared to wildtype.
      CD200R agonist treatment was performed in male C57Bl/6J mice to validate the role
      of the CD200-CD200R axis in arteriogenesis. CD200R agonist treatment after
      unilateral femoral artery ligation resulted in a significant decrease in vessel
      geometry, perfusion recovery and T lymphocyte influx at day 7 compared to isotype
      treatment. In this study, we show a causal role for the CD200-CD200R inhibitory
      axis in arteriogenesis in a murine hindlimb ischemia model. Lack of CD200R
      signaling is accompanied by increased T lymphocyte recruitment to the collateral
      vasculature and results in enlargement of preexisting collateral arteries. 

PMID- 24897501
TI  - Using a multi-trait approach to manipulate plant functional diversity in a
      biodiversity-ecosystem function experiment.
AB  - A frequent pattern emerging from biodiversity-ecosystem function studies is that
      functional group richness enhances ecosystem functions such as primary
      productivity. However, the manipulation of functional group richness goes along
      with major disadvantages like the transformation of functional trait data into
      categories or the exclusion of functional differences between organisms in the
      same group. In a mesocosm study we manipulated plant functional diversity based
      on the multi-trait Functional Diversity (FD)-approach of Petchey and Gaston by
      using database data of seven functional traits and information on the origin of
      the species in terms of being native or exotic. Along a gradient ranging from low
      to high FD we planted 40 randomly selected eight-species mixtures under
      controlled conditions. We found a significant positive linear correlation of FD
      with aboveground productivity and a negative correlation with invasibility of the
      plant communities. Based on community-weighted mean calculations for each
      functional trait, we figured out that the traits N-fixation and species origin,
      i.e. being native or exotic, played the most important role for community
      productivity. Our results suggest that the identification of the impact of
      functional trait diversity and the relative contributions of relevant traits is
      essential for a mechanistic understanding of the role of biodiversity for
      ecosystem functions such as aboveground biomass production and resistance against
      invasion. 

PMID- 24897502
TI  - Monitoring wildlife-vehicle collisions in the information age: how smartphones
      can improve data collection.
AB  - BACKGROUND: Currently there is a critical need for accurate and standardized
      wildlife-vehicle collision data, because it is the underpinning of mitigation
      projects that protect both drivers and wildlife. Gathering data can be
      challenging because wildlife-vehicle collisions occur over broad areas, during
      all seasons of the year, and in large numbers. Collecting data of this magnitude
      requires an efficient data collection system. Presently there is no widely
      adopted system that is both efficient and accurate. METHODOLOGY/PRINCIPAL
      FINDINGS: Our objective was to develop and test an integrated smartphone-based
      system for reporting wildlife-vehicle collision data. The WVC Reporter system we
      developed consisted of a mobile web application for data collection, a database
      for centralized storage of data, and a desktop web application for viewing data.
      The smartphones that we tested for use with the application produced accurate
      locations (median error = 4.6-5.2 m), and reduced location error 99% versus
      reporting only the highway/marker. Additionally, mean times for data entry using
      the mobile web application (22.0-26.5 s) were substantially shorter than using
      the pen/paper method (52 s). We also found the pen/paper method had a data entry
      error rate of 10% and those errors were virtually eliminated using the mobile web
      application. During the first year of use, 6,822 animal carcasses were reported
      using WVC Reporter. The desktop web application improved access to WVC data and
      allowed users to easily visualize wildlife-vehicle collision patterns at multiple
      scales. CONCLUSIONS/SIGNIFICANCE: The WVC Reporter integrated several modern
      technologies into a seamless method for collecting, managing, and using WVC data.
      As a result, the system increased efficiency in reporting, improved accuracy, and
      enhanced visualization of data. The development costs for the system were minor
      relative to the potential benefits of having spatially accurate and temporally
      current wildlife-vehicle collision data.

PMID- 24897503
TI  - Genotype characterization of commonly used Newcastle disease virus vaccine
      strains of India.
AB  - Newcastle disease is an avian pathogen causing severe economic losses to the
      Indian poultry industry due to recurring outbreaks in vaccinated and unvaccinated
      flocks. India being an endemic country, advocates vaccination against the virus
      using lentogenic and mesogenic strains. Two virus strains which are commonly used
      for vaccination are strain F (a lentogenic virus) and strain R2B (a mesogenic
      virus). Strain F is given to 0-7 days old chicks and R2B is given to older birds
      which are around 6-8 weeks old. To understand the genetic makeup of these two
      strains, a complete genome study and phylogenetic analysis of the F, HN genes of
      these vaccine strains were carried out. Both the viral strains had a genome
      length of 15,186 nucleotides and consisted of six genes with conserved
      complimentary 3' leader and 5' trailer regions. The fusion protein cleavage site
      of strain F is GGRQGRL and strain R2B is RRQKRF. Although both the viral strains
      had different virulence attributes, the length of the HN protein was similar with
      577 amino acids. Phylogenetic analysis of F, HN and complete genome sequences
      grouped these two strains in genotype II category which are considered as early
      genotypes and corroborated with their years of isolation. 

PMID- 24897504
TI  - Effects of prophylactic and therapeutic paracetamol treatment during vaccination
      on hepatitis B antibody levels in adults: two open-label, randomized controlled
      trials.
AB  - Worldwide, paracetamol is administered as a remedy for complaints that occur
      after vaccination. Recently published results indicate that paracetamol inhibits
      the vaccination response in infants when given prior to vaccination. The goal of
      this study was to establish whether paracetamol exerts similar effects in young
      adults. In addition, the effect of timing of paracetamol intake was investigated.
      In two randomized, controlled, open-label studies 496 healthy young adults were
      randomly assigned to three groups. The study groups received paracetamol for 24
      hours starting at the time of (prophylactic use) - or 6 hours after (therapeutic
      use) the primary (0 month) and first booster (1 month) hepatitis B vaccination.
      The control group received no paracetamol. None of the participants used
      paracetamol around the second booster (6 months) vaccination. Anti-HBs levels
      were measured prior to and one month after the second booster vaccination on
      ADVIA Centaur XP. One month after the second booster vaccination, the anti-HBs
      level in the prophylactic paracetamol group was significantly lower (p = 0.048)
      than the level in the control group (4257 mIU/mL vs. 5768 mIU/mL). The anti-HBs
      level in the therapeutic paracetamol group (4958 mIU/mL) was not different (p =
      0.34) from the level in the control group. Only prophylactic paracetamol
      treatment, and not therapeutic treatment, during vaccination has a negative
      influence on the antibody concentration after hepatitis B vaccination in adults.
      These findings prompt to consider therapeutic instead of prophylactic treatment
      to ensure maximal vaccination efficacy and retain the possibility to treat pain
      and fever after vaccination. TRIAL REGISTRATION: Controlled-Trials.com
      ISRCTN03576945.

PMID- 24897506
TI  - Bone marrow stromal cell-fueled multiple myeloma growth and osteoclastogenesis
      are sustained by protein kinase CK2.

PMID- 24897505
TI  - Evolutionary trajectories of hyperdiploid ALL in monozygotic twins.
AB  - Identical twins have provided unique insights on timing or sequence of genetic
      events in acute lymphoblastic leukaemia (ALL). To date, this has mainly focused
      on ALL with MLL or ETV6-RUNX1 fusions, with hyperdiploid ALL remaining less well
      characterised. We examined three pairs of monozygotic twins, two concordant and
      one discordant for hyperdiploid ALL, for single-nucleotide polymorphism (SNP)
      defined copy number alterations (CNAs), IGH/L plus TCR gene rearrangements and
      mutations in NRAS, KRAS, FLT3 and PTPN11 genes. We performed whole exome
      sequencing in one concordant twin pair. Potential 'driver' CNAs were low, 0-3 per
      case, and all were different within a pair. One patient had an NRAS mutation that
      was lacking from leukaemic cells of the twin sibling. By exome sequencing, there
      were 12 nonsynonymous mutations found in one twin and 5 in the other, one of
      which in SCL44A2 was shared or identical. Concordant pairs had some identical
      IGH/L and TCR rearrangements. In the twin pair with discordant hyperdiploid ALL,
      the healthy co-twin had persistent low level hyperdiploid CD19+ cells that lacked
      a CNA present in the ALL cells of her sibling. From these data, we propose that
      hyperdiploid ALL arises in a pre-B cell in utero and mutational changes necessary
      for clinical ALL accumulate subclonally and postnatally. 

PMID- 24897511
TI  - Mouse pups discriminate food gnawed by conspecifics.
AB  - Eighteen- and 24-day-old albino mice, the former experiencing their first direct
      contact with solid food, were offered a set of food pellets, some of which had
      been gnawed by adult conspecifics of various conditions. No adult was present
      during the test. The subjects of both ages clearly preferred intact pellets over
      pellets gnawed by mice, although familiarity with the donor of residual cues had
      a positive effect on Day 24 (Experiment 1). When pellets were treated with garlic
      extract, an initially aversive compound, the younger subjects showed initial
      preference for pellets gnawed by the dam over intact pellets, although avoidance
      of gnawed pellets was a main result again (Experiment 2). Tendency of the mouse
      to avoid crowding near a feeding point seems a likely explanation of this
      residual-cue avoidance, which also seems inversely related to neophobia. A
      behavioural difference from the rat is suggested. 

PMID- 24897507
TI  - Activating c-KIT mutations confer oncogenic cooperativity and rescue RUNX1/ETO
      induced DNA damage and apoptosis in human primary CD34+ hematopoietic
      progenitors.
AB  - The RUNX1/ETO (RE) fusion protein, which originates from the t(8;21) chromosomal
      rearrangement, is one of the most frequent translocation products found in de
      novo acute myeloid leukemia (AML). In RE leukemias, activated forms of the c-KIT
      tyrosine kinase receptor are frequently found, thereby suggesting oncogenic
      cooperativity between these oncoproteins in the development and maintenance of
      t(8;21) malignancies. In this report, we show that activated c-KIT cooperates
      with a C-terminal truncated variant of RE, REtr, to expand human CD34+
      hematopoietic progenitors ex vivo. CD34+ cells expressing both oncogenes resemble
      the AML-M2 myeloblastic cell phenotype, in contrast to REtr-expressing cells
      which largely undergo granulocytic differentiation. Oncogenic c-KIT amplifies
      REtr-depended clonogenic growth and protects cells from exhaustion. Activated c
      KIT reverts REtr-induced DNA damage and apoptosis. In the presence of activated c
      KIT, REtr-downregulated DNA-repair genes are re-expressed leading to an
      enhancement of DNA-repair efficiency via homologous recombination. Together, our
      results provide new mechanistic insight into REtr and c-KIT oncogenic
      cooperativity and suggest that augmented DNA repair accounts for the increased
      chemoresistance observed in t(8;21)-positive AML patients with activated c-KIT
      mutations. This cell-protective mechanism might represent a new therapeutic
      target, as REtr cells with activated c-KIT are highly sensitive to
      pharmacological inhibitors of DNA repair. 

PMID- 24897512
TI  - An investigation of the role of the hippocampus and the amygdala in the encoding
      of a serial pattern: Effects of a long inter-element interval.
AB  - Previous research has provided convincing evidence that rats can learn to
      anticipate each element of a stimulus series consisting of differing
      reinforcement quantities. The present experiment examined the effects of
      electrolytic lesions of the hippocampus, amygdala, or combined hippocampal and
      amygdala lesions on the acquisition of a 14-7-3-0 monotonic pattern with a 5 min
      inter-element interval. Anticipation was operationally defined as faster running
      on 14- than on 7-pellet elements, 7- than on 3-pellet elements, and 3- than 0
      pellet elements. Male Sprague-Dawley rats (sham and lesioned) received two trials
      a day for 30 days on the 14-7-3-0 pattern of food pellets. Anticipatory tracking
      developed rapidly in the control animals and not until the end of training in the
      hippocampus + amygdala-lesioned rats, while the rate of acquisition in the single
      lesion groups was intermediate between the two. The results are discussed in
      terms of temporal and working memory processes. Mediation of the temporal and
      affective attributes of memory are considered for each structure. The present
      experiment provided additional evidence for a hippocampal role in maintenance of
      a temporal record of the elements of the series, thus providing the rat with the
      ability to track which stimulus elements have been presented and to anticipate
      future elements. Finally, via a role in processing the affective and reinforcing
      properties of the task, the amygdala appears to play a role in mnemonic
      processes. 

PMID- 24897509
TI  - Oral medicines for children in the European paediatric investigation plans.
AB  - INTRODUCTION: Pharmaceutical industry is no longer allowed to develop new
      medicines for use in adults only, as the 2007 Paediatric Regulation requires
      children to be considered also. The plans for such paediatric development called
      Paediatric Investigation Plans (PIPs) are subject to agreement by the European
      Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study
      was to evaluate the key characteristics of oral paediatric medicines in the PIPs
      and the changes implemented as a result of the EMA/PDCO review. METHODS: All PIPs
      agreed by 31 December 2011 were identified through a proprietary EMA-database.
      PIPs were included if they contained an agreed proposal to develop an oral
      medicine for children 0 to 11 years. Information on the therapeutic area (EMA
      classification system); target age range (as defined by industry) and
      pharmaceutical characteristics (active substance, dosage form(s) as listed in the
      PIP, strength of each dosage form, excipients in each strength of each dosage
      form) was extracted from the EMA website or the EMA/PDCO assessment reports.
      RESULTS: A hundred and fifty PIPs were included corresponding to 16 therapeutic
      areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs
      (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a
      specific composition/strength that were stored as a solid but swallowed as a
      liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of
      13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms
      with a specific composition/strength. For many PIPs, the target age range was
      widened and the excipient composition and usability aspects modified. CONCLUSION:
      The EMA/PDCO review realized an increase in the number of requirements for the
      development of oral dosage forms and a larger increase in the number of dosage
      forms with a specific composition/strength, both targeting younger children.
      Changes to their pharmaceutical design were less profound.

PMID- 24897513
TI  - Rearing environment and radial maze exploration in mice.
AB  - The effect of an enriched rearing environment on exploration of 4- and 8-arm
      radial mazes was investigated in CD-1 mice. Subjects in enriched (EC) and
      standard (SC) environmental conditions were socially reared with the exception
      that various objects and a running wheel were added into the EC cages. Non
      deprived subjects were allowed to explore individually an appropriate maze for 10
      min periods on two successive days (Days 1 and 2 of the experiment). After the
      second exploration session subjects were deprived of water for 12 h before the
      test which was administered on Day 3 of the experiment. Subjects from both groups
      performed similarly in the 4-arm radial maze, finding the arm containing water
      with comparable latency and erroneous entries to other, not containing water,
      arms. However, the more complex, 8-arm radial maze significantly differentiated
      the behaviour of both groups. EC subjects showed faster habituation to the maze
      than SC subjects, decreasing significantly their locomotor behaviour during
      second exploratory session. During the test, EC subjects found and drank water
      within significantly shorter time, making fewer errors. It is suggested that
      subtle behavioural changes caused by different rearing environments might be more
      readily detectable in the early phases of solving more complex behavioural tasks
      by mildly motivated animals. 

PMID- 24897514
TI  - Within-session response patterns when rats press levers for water: Effects of
      component stimuli and experimental environment.
AB  - Rats pressed levers for water reinforcers delivered by multiple variable interval
      one-minute variable interval one-minute schedules. Experiment 1 manipulated the
      stimuli signalling the components of the multiple schedule. Experiment 2 varied
      the experimental environment. Responding changed significantly within the session
      during every condition of both experiments. Manipulating the component stimuli
      significantly altered the within-session pattern of responding; varying the
      environment did not. These results show within-session patterns of responding
      occur when subjects respond for water reinforcers. They also imply that
      contextually-based explanations for within-sessions patterns of responding are
      unlikely. 

PMID- 24897515
TI  - Lack of effect of prefeeding on food-reinforced temporal response differentiation
      and progressive ratio responding.
AB  - To investigate the effects of various prefeeding intervals on operant performance
      (time of partial satiation prior to assessment), adult male Sprague-Dawley rats
      were trained on two operant tasks: a temporal response differentiation (TRD) task
      thought to measure time discrimination and a progressive ratio (PR) task thought
      to measure motivation to work for food reinforcers. Endpoints included percent
      task completed, response rate, accuracy (TRD only) and breakpoint (PR only).
      During the two week baseline period, subjects were fed their daily allotment of
      food (9-12 g) 23 h prior to assessment. In subsequent weeks, subjects were
      partially satiated by prefeeding the daily allotment of food from 0.25 h to 6 h
      prior to operant assessment. Prefeeding had no significant effects on performance
      of either operant task. This study extends previous findings by demonstrating no
      effects of prefeeding interval on two dissimilar operant behaviors. Thus, the
      results do not support deprivation interval as a measure of hunger. A more
      accurate measure of hunger might be provided by the use of body weight or
      percentage thereof. 

PMID- 24897508
TI  - Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo
      expansion of regulatory T cells and permits peripheral blood stem cell
      transplantation from haploidentical donors.
AB  - Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)
      haploidentical family donors is a promising therapeutic option for high-risk
      hematologic malignancies. Here we explored in 121 patients, mostly with advanced
      stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of
      graft-versus-host disease (GvHD) to allow the infusion of unmanipulated
      peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors
      (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on
      treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin
      Fresenius (ATG-F), rituximab and oral administration of sirolimus and
      mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and
      19 days after HSCT, respectively, and full donor chimerism was documented in
      patients' bone marrow since the first post-transplant evaluation. T-cell immune
      reconstitution was rapid, and high frequencies of circulating functional T
      regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence
      of acute GvHD grade II-IV was 35%, and occurrence and severity correlated
      negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after
      HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall
      survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F
      rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing
      the infusion of unmanipulated haploidentical PBSC grafts. 

PMID- 24897516
TI  - Evolution of the optical releasers for aggressive behavior in cave-dwelling
      Astyanax fasciatus (Teleostei, Characidae).
AB  - Epigean and blind cave-dwelling populations of the characid Astyanax fasciatus
      differ in their agonistic behavior. Epigean specimens are characterized by
      intense aggressive behavior and territoriality in the laboratory, whereas the
      blind cave fishes are rarely aggressive and have totally lost the territorial
      behavior. These behavioral changes are genetically based. In the present study, a
      comparative analysis of the optical releasers for aggressive behavior has been
      performed in both epigean and cave-dwelling populations. It was expected that the
      regression of aggressive behavior should be accompanied by the regression of the
      genetically fixed optical releasers for aggression in the cave specimens. For the
      analysis of cave fishes, well-eyed F1-hybrids of cave and epigean specimens
      (Pachon * Teapao) as well as phylogenetically young cave specimens (Micos)
      selected for large eyes, have been used. In epigean specimens, aggression is most
      intensely released by a combination of the signals 'natural shape' and
      'locomotion'. The cave populations exhibit a partial regression of the releaser
      'natural shape'. 'Locomotion', however, has become a more effective releaser for
      aggression in cave fishes than it has in their epigean relatives. The results are
      discussed with respect to their evolutionary significance. 

PMID- 24897517
TI  - Responsiveness to a novel preening stimulus long after partial beak amputation
      (beak trimming) in laying hens.
AB  - Thirty beak-trimmed and thirty intact hens were reared in mixed groups and
      individually housed in battery cages; partial beak amputation took place 6 weeks
      after hatching. All hens were tested with a novel stimulus when they were 42
      weeks old: a small paper sticker (36 mm(2)) was attached to the distal parts of
      the feathers at the back of the hen. It took beak-trimmed hens on average 27
      seconds and the intact ones 8 s to start preening the sticker. This difference
      was statistically significant. Beak-trimmed hens tended to preen the sticker less
      than intact birds. Lighting conditions had no effect on the response latency,
      while the amount of eating and drinking did not differ between both groups,
      indicating that lack of light, anxiety or other types of disturbances did not
      affect the preening responses. It is concluded that beak trimming has long
      lasting consequences in reducing the responsiveness to a novel preening stimulus.
      This result is in agreement with the long term passivity in beak-trimmed hens
      found in other studies. The development of a reduced responsiveness as a result
      of beak trimming suggests poor animal welfare. 

PMID- 24897518
TI  - Spontaneous locomotor activity of Drosophila melanogaster flies at various
      gravity levels (0 g, 1 g, 1.8 g) during parabolic flights.
AB  - The spontaneous locomotor activity of young, middle-aged and old Drosophila
      melanogaster of both sexes has been videorecorded during three parabolic flights
      separated by one-day intervals. Fast shifts between 0 g, 1 g and 1.8 g phases are
      obtained during parabolic flights. Results showed that the activity scores were
      higher at 0 g during the first flight, but that this effect of microgravity was
      erased during the two next flights. It may be concluded that flies showed a
      transient form of reactivity to a new environment, i.e. to repeated rapid
      variations of gravity levels. 

PMID- 24897519
TI  - Effect of early trough familiarity on the creep feeding behaviour in suckling
      piglets and after weaning.
AB  - The incidence of an early contact with trough and/or feed on creep feeding
      behaviour was evaluated before and after weaning (day 28) using 28 litters Large
      White X Pietrain. During the second week of life, litters were allocated to one
      of the four treatments: empty trough (group T), trough supplied with feed (group
      TF), feed supplied on floor (group F), and nothing (group N). Between days 14 and
      28, all groups were supplied with trough and feed for 90 minutes per day.
      Behavioural recordings were carried out every two days during the feed supply.
      Over weeks 3 and 4, creep feed intake was highly variable between litters (range
      0-2382 g) and within litters (range 0-674 g/piglet). Feeding activity started
      around day 21, concerned a low number of littermates (< 50%), and was associated
      with a strong exploration and social behaviour around the trough. Females were
      more implicated than castrated males (P < 0.05) and tended to show higher
      estimated creep feed intake (P < 0.10). The number of feeding acts (10 vs. 5),
      the percentage of littermates engaged in feeding behaviour (20% vs. 10%) and the
      feed intake (300 g vs. 100 g) tended to be higher in the TF than in the other
      groups (P < 0.1). After weaning, treatment had no effect on the feed intake.
      However, females exhibited a higher feed intake (P < 0.05) during the first 4
      days following weaning (day 1: 20.5 g vs. 12 g; days 2-4: 254 g vs. 185 g), and
      less feed was ingested (P < 0.05) the first day in piglets exhibiting no creep
      feed behaviour during the behavioural recordings of the suckling period. Results
      suggest wide adaptive capacities of weaned piglets although an effect of learning
      cannot be eliminated. 

PMID- 24897520
TI  - The variable loop 3 in the envelope glycoprotein is critical for the atypical
      coreceptor usage of an HIV-1 strain.
AB  - The majority of HIV-1 strains enter CD4+ T cells using the CCR5 and/or CXCR4 co
      receptor. However, we recently identified a transmitted/founder (T/F) virus
      (ZP6248) that efficiently used an alternative coreceptor GPR15, rather than
      commonly used CXCR4 and CCR5, to establish clinical infection. To understand
      which regions in the env gene were critical for the atypical coreceptor usage, we
      generated a set of V3 mutants and determined their infectivity in GHOST cells
      that expressed different coreceptors. When the variable loop 3 (V3) in YU2 was
      replaced with the ZP6248 V3 (YU2.6248V3), the chimera YU2.6248V3 infected GPR15+
      cells but not CCR5+ cells. To determine which amino acids in V3 was responsible
      for this phenotype change, each of the eight amino acids that differed from the
      subtype B consensus V3 was substituted with alanine. The G306A and S322A
      mutations significantly reduced the replication capacity of YU2.6248V3 in GPR15+
      cells, while all other alanine substitutions at positions 307, 314, 315, 316, 317
      and 318 completely abrogated the infectivity of YU2.6248V3 in GPR15+ cells. The
      E314A mutation, as the E314G mutation reported before, also rendered the
      YU2.6248V3 infectious in CCR5+ cells, while none of other alanine mutants could
      infect CCR5+ cells. These results demonstrated that amino acids in ZP6248 V3
      might form a unique conformation that was critical for the interaction with GPR15
      while the amino acids at position 314 in the V3 crown of ZP6248 played a key role
      in interaction with both CCR5 and GPR15. The unique phenotypes of ZP6248 can
      serve as a model to understand how HIV-1 explores the diverse coreceptor
      reservoir through novel genetic variants to establish clinical infection.

PMID- 24897522
TI  - Biochar from sugarcane filtercake reduces soil CO2 emissions relative to raw
      residue and improves water retention and nutrient availability in a highly
      weathered tropical soil.
AB  - In Brazil, the degradation of nutrient-poor Ferralsols limits productivity and
      drives agricultural expansion into pristine areas. However, returning
      agricultural residues to the soil in a stabilized form may offer opportunities
      for maintaining or improving soil quality, even under conditions that typically
      promote carbon loss. We examined the use of biochar made from filtercake (a
      byproduct of sugarcane processing) on the physicochemical properties of a
      cultivated tropical soil. Filtercake was pyrolyzed at 575 degrees C for 3 h
      yielding a biochar with increased surface area and porosity compared to the raw
      filtercake. Filtercake biochar was primarily composed of aromatic carbon, with
      some residual cellulose and hemicellulose. In a three-week laboratory incubation,
      CO2 effluxes from a highly weathered Ferralsol soil amended with 5% biochar (dry
      weight, d.w.) were roughly four-fold higher than the soil-only control, but 23
      fold lower than CO2 effluxes from soil amended with 5% (d.w.) raw filtercake. We
      also applied vinasse, a carbon-rich liquid waste from bioethanol production
      typically utilized as a fertilizer on sugarcane soils, to filtercake- and biochar
      amended soils. Total CO2 efflux from the biochar-amended soil in response to
      vinasse application was only 5% of the efflux when vinasse was applied to soil
      amended with raw filtercake. Furthermore, mixtures of 5 or 10% biochar (d.w.) in
      this highly weathered tropical soil significantly increased water retention
      within the plant-available range and also improved nutrient availability.
      Accordingly, application of sugarcane filtercake as biochar, with or without
      vinasse application, may better satisfy soil management objectives than
      filtercake applied to soils in its raw form, and may help to build soil carbon
      stocks in sugarcane-cultivating regions. 

PMID- 24897524
TI  - "Beyond the fields we know...": exploring and developing scalar timing theory.
AB  - The article discusses three areas that appear neglected or underdeveloped in
      current treatments of scalar timing theory (SET). In particular, questions about
      where variance in the SET system comes from, and how memory and decision
      processes operate within SET are discussed. The article suggests a number of
      possible experiments with humans, some based on pilot work which is described,
      that may clarify all three areas to some degree. Methods derived from
      conventional studies of memory are suggested as providing techniques for
      investigating the operation of memory and decision processes within the SET
      model, both areas previously considered somewhat inaccessible. In general, the
      tripartite division of SET into clock, memory, and decision processes is
      advocated as a useful general framework for studying timing, including questions
      related to its neurobiological basis, whether or not data always conform to SET
      predictions, although more needs to be known about how all three parts of the SET
      system operate. 

PMID- 24897523
TI  - Self-reported adherence to medical treatment, breastfeeding behaviour, and
      disease activity during the postpartum period in women with Crohn's disease.
AB  - OBJECTIVES: Adherence to medical treatment among women with Crohn's disease (CD)
      in the postpartum period has never been examined. The impact of breast-feeding on
      disease activity remains controversial. We aimed to assess rates of non-adherence
      to medical treatment among women with CD in the postpartum period. Further, to
      assess breast-feeding rates and the impact of breast-feeding on the risk of
      relapse. METHODS: Within a population of 1.6 million, we identified 154 women
      with CD who had given birth within a 6-year period. We combined questionnaire
      data, data from medical records and public register data. We used logistic
      regression to estimate prevalence odds ratios (POR) for non-adherence, relapse
      and breast-feeding according to different predictors. RESULTS: Among 105 (80%)
      respondents, 59 (56%) reported taking medication. Of these, 66.1% reported to be
      adherent to medical treatment. Fear of medication transmission to the breast milk
      was stated as the reason for non-adherence in 60%. Those who received counselling
      regarding medical treatment were less likely to be non-adherent (POR 0.55, 95%
      confidence interval [CI] 0.1-2.5). In total, 87.6% were breast-feeding. Breast
      feeding rates did not vary by medical treatment. Predictors for relapse in CD
      were smoking (POR 1.85, 95% CI 0.62-5.54) and non-adherence among medical treated
      (POR 1.25, 95% CI 0.26-6.00). Breast-feeding seemed protective against relapse
      (POR 0.33, 95% CI 0.10-1.26). CONCLUSIONS: Adherence to medical treatment in the
      postpartum period was high, and counselling seemed to increase adherence. Relapse
      may be explained by non-adherence or smoking while breast-feeding seemed
      protective.

PMID- 24897521
TI  - Deep sequencing reveals new aspects of progesterone receptor signaling in breast
      cancer cells.
AB  - Despite the pleiotropic effects of the progesterone receptor in breast cancer,
      the molecular mechanisms in play remain largely unknown. To gain a global view of
      the PR-orchestrated networks, we used next-generation sequencing to determine the
      progestin-regulated transcriptome in T47D breast cancer cells. We identify a
      large number of PR target genes involved in critical cellular programs, such as
      regulation of transcription, apoptosis, cell motion and angiogenesis. Integration
      of the transcriptomic data with the PR-binding profiling of hormonally treated
      cells identifies numerous components of the small-GTPases signaling pathways as
      direct PR targets. Progestin-induced deregulation of the small GTPases may
      contribute to the PR's role in mammary tumorigenesis. Transcript expression
      analysis reveals significant expression changes of specific transcript variants
      in response to the extracellular hormonal stimulus. Using the NET1 gene as an
      example, we show that the PR can dictate alternative promoter usage leading to
      the upregulation of an isoform that may play a role in metastatic breast cancer.
      Future studies should aim to characterize these selectively regulated variants
      and evaluate their clinical utility in prognosis and targeted therapy of
      hormonally responsive breast tumors. 

PMID- 24897525
TI  - Gap timing and the spectral timing model.
AB  - A hypothesized mechanism underlying gap timing was implemented in the Spectral
      Timing Model [Grossberg, S., Schmajuk, N., 1989. Neural dynamics of adaptive
      timing and temporal discrimination during associative learning. Neural Netw. 2,
      79-102] , a neural network timing model. The activation of the network nodes was
      made to decay in the absence of the timed signal, causing the model to shift its
      peak response time in a fashion similar to that shown in animal subjects. The
      model was then able to accurately simulate a parametric study of gap timing
      [Cabeza de Vaca, S., Brown, B., Hemmes, N., 1994. Internal clock and memory
      processes in aminal timing. J. Exp. Psychol.: Anim. Behav. Process. 20 (2), 184
      198]. The addition of a memory decay process appears to produce the correct
      pattern of results in both Scalar Expectancy Theory models and in the Spectral
      Timing Model, and the fact that the same process should be effective in two such
      disparate models argues strongly that process reflects a true aspect of animal
      cognition. 

PMID- 24897526
TI  - Timing in simple conditioning and occasion setting: a neural network approach.
AB  - We present a neural network model of Pavlovian conditioning in which a timing
      mechanism, by which a CS can predict when the US is presented, activates an
      architecture in which a stimulus acts as a simple CS and/or as an occasion
      setter. In the model, stimuli evoke multiple traces of different duration and
      amplitude, peaking at different times after CS presentation [Grossberg and
      Schmajuk, 1989. Neural Netw. 2, 79-102]. These traces compete to become
      associated directly and indirectly (through hidden units) with the US [Schmajuk
      and DiCarlo, 1992. Psychol. Rev. 99, 268-305]. The output of the system predicts
      the value, moment, and duration of presentation of reinforcement. Importantly, in
      contrast to the model by Schmajuk and DiCarlo [Schmajuk and DiCarlo, 1992.
      Psychol. Rev. 99, 268-305], in the present model a stimulus may assume different
      roles (simple CS, occasion setter, or both) at different time moments. Moreover,
      while in the Schmajuk and DiCarlo model [Schmajuk and DiCarlo, 1992. Psychol.
      Rev. 99, 268-305], competition between CSs is purely associative, in the present
      model competition between CSs is both associative and temporal. CSs compete to
      predict not only the presence and the intensity of the US, but also its temporal
      characteristics: time of presentation and duration. The model is able to address
      both the temporal and associative properties of simple conditioning, compound
      conditioning, and occasion setting. 

PMID- 24897528
TI  - Multiple approaches to investigate the existence of an internal clock using
      attentional resources.
AB  - The attentional model of time estimation assumes that specific mechanisms are
      involved when subjects explicitly process temporal information. Temporal
      judgments would depend on the amount of attentional resources allocated to a
      temporal processor (also called timer). The present paper provides some evidence
      in favor of the existence of such a processor. The first part shows the
      importance of attention for an efficient functioning of the timer, based on a
      cumulative mechanism. The second part is centered on the slow brain potential
      changes recorded over the scalp when subjects focus their attention on the
      temporal parameters of a task. The main result is the existence of a relationship
      between the amplitude of the brain waves and the temporal performances. 

PMID- 24897527
TI  - What's an internal clock for? From temporal information processing to temporal
      processing of information.
AB  - The existence of an internal clock and its involvement in information processing
      has been investigated in humans using the experimental protocol of Treisman et
      al. (1990) [Treisman et al., 1990. Perception, 19, 705-743]. In this protocol, a
      periodical stimulation, which is assumed to drive an internal clock, is delivered
      during a reaction time (RT) task. The accelerating or slowing down effects of the
      periodical stimulation, according to its frequency, allowed an estimate to be
      made of a simple harmonic of the frequency of the internal clock. The estimate
      was close to 21 Hz. In the framework of the serial model of information
      processing, the present work investigates the involvement of the internal clock
      in the transmission of information between processing stages during RT. The data
      tend to support the idea that the internal clock allows the transfer of
      information from one stage to the next one at definite moments only, periodically
      distributed in time. According to our results, and recent data from the
      literature on electric cortical oscillations, we propose a model of an internal
      clock sending periodic inhibition, which would permit an increased signal/noise
      ratio in the processing and the transmission of information in the central
      nervous system. 

PMID- 24897529
TI  - Preference for sequences of rewards: further tests of a parallel discounting
      model.
AB  - Brunner and Gibbon [Brunner, D., Gibbon, J., 1995. Anim. Behav. 50, 1627-1634]
      studied rats' choices between sequences of equal numbers of rewards that differed
      in their temporal arrangement. Rats' preferences were well accounted for by a
      parallel discounting model of aggregate food value in which the sequence value is
      the simple sum of the hyperbolically discounted value of the individual rewards
      [Mazur, J.E., 1984. J. Exp. Anal. Behav. 46, 67-77]. Three experiments reported
      here extend their work to sequences of unequal number of rewards and test the
      specific prediction that rats prefer sequences that get worse with time over
      sequences that improve, given that the total reward rate is the same. Choice
      functions from this and other two experiments that offered choice between unequal
      reward numbers were S-shaped and supported a signal detection-like model in which
      the value of each option obeys the parallel discounting model. 

PMID- 24897530
TI  - Scheduling reinforcement about once a day.
AB  - A pigeon earned its daily food by pecking a key according to reinforcement
      schedules that produced food about once per day. Fixed-interval (FI), Fixed-time
      (FT), and various complex schedules were arranged to demonstrate the degree to
      which a scalloped pattern of responding remained. Pausing continued until about
      an hour before the reinforcer could be earned for FIs of 12, 24, and 48 h.
      Pausing was not as long for FIs of 18, 19, and 23 h. Pausing of about 24 h was
      seen for FI 36 h. FT 24 h produced continued responding but at a diminished
      frequency. The pattern of responding was strongly controlled by the schedule of
      reinforcement and seemed relatively independent of the cycle of human activity in
      the surrounding laboratory. Effects of added ratio contingencies and of signaling
      the availability of reinforcement in FT were also examined. Signaled FTs of 5 min
      3 h produced more responding during the signal (autoshaping) than did FTs of 19
      or 24 h. 

PMID- 24897531
TI  - Timing and choice in concurrent chains.
AB  - To investigate the role of timing processes in choice, we used a new procedure
      that provided simultaneous measures of ongoing choice and timing behavior.
      Pigeons responded in a peak procedure in which the delays to reinforcement
      signaled by red and green center-key stimuli were 10 and 20, or 20 and 40 s.
      After 25 sessions of training, the peak procedure was embedded within concurrent
      chains: The inter-trial interval was replaced by a choice phase in which the two
      side keys were illuminated white; responses to the left and right keys
      occasionally changed the center-key to red or green, respectively; and the
      terminal links signaled by the center-key stimuli were identical to the trials of
      the peak procedure. The temporal control of responding on no-food trials was the
      same regardless of whether the no-food trials occurred in the peak procedure or
      as the terminal links of concurrent chains. After an intervening condition with
      the peak procedure in which the delay for the 10 s stimulus was changed to 40 s
      (or vice versa), the pigeons were returned to concurrent chains. Choice
      responding did not reflect the changed delay, despite the fact that the pigeons
      timed the delays in both terminal links accurately as indexed by responding on no
      food trials. This result challenges current accounts of choice based on timing
      processes, such as scalar expectancy theory, which assume that choice responding
      is mediated by a representation of terminal link delays to reinforcement.
      Apparently, pigeons' choice and timing behavior in a single session can be
      controlled by temporal information from different temporal epochs. 

PMID- 24897532
TI  - A clock not wound runs down.
AB  - Seven pigeons were trained to respond on one key during the first half of a 60-s
      trial, and on another during the second half, to test the prediction that the
      rate of the internal pacemaker should slow in the absence of reward. The relative
      probability of responding was well-described by Erlang distributions, which
      yielded as parameters the period of the pacemaker and the criterial number of
      counts for switching to the second key. During a subsequent period of extinction
      the period increased linearly with time in extinction, and the criterial count
      decreased. This slowing of the pacemaker was predicted by the Behavioral Theory
      of timing, but not by other theories. 

PMID- 24897533
TI  - Attention and timing: dual-task performance in pigeons.
AB  - Pigeons were exposed to an analog of a 'dual-task' procedure used to test
      attentional models of timing in humans. After separate training on an auditory
      duration discrimination and on a variable ratio (VR) schedule, VR episodes
      lasting for 5 s were superimposed on the stimuli to be timed, either early (E) or
      late (L) during the trial. Trials with VR yielded underestimation of the target
      durations (increased % of 'short' choices), relative to trials without VR, and
      this effect was stronger under the L than under the E condition. Data were
      similar to those collected with humans and support attentional models of timing
      according to which the simultaneous non-timing task uses processing resources
      which are diverted from the timing mechanisms. 

PMID- 24897534
TI  - Reinforcement-induced within-trial resetting of an internal clock.
AB  - Rats were trained on a modified peak-interval timing procedure in which three
      response levers were individually associated with different criterion durations
      (10, 30 and 90 s) following the onset of a tone stimulus. Delivery of response
      dependent reinforcement for each duration was independent of both the responding
      and the delivery of reinforcement for the other durations, such that the tone
      stimulus stayed on during food delivery, and no change in the primed
      reinforcement times occurred. We report here that the delivery of reinforcement
      at an earlier criterion duration produces a rightward shift in the temporal
      response functions for later durations by the amount of time that has already
      elapsed in the trial. This reset in temporal accumulation produces large
      discrepancies between the programmed and expected (peak) times of reinforcement
      and suggests that rats are unable to make conditional reinforcement-based
      discriminations of interval duration. 

PMID- 24897535
TI  - Behavioral adjustment to modifications in the temporal parameters of the
      environment.
AB  - We study the dynamics of behavioral transitions when European starlings (Sturnus
      vulgaris) experience stepwise changes in the value of a meaningful time interval.
      Subjects were primed to respond at a certain time T1. After extensive training,
      the primed time changed to a new value T2. In Experiment 1 subjects were
      reinforced on 40% of the trials and they experienced a single transition which
      lasted until asymptotic behavior was reached. Starlings showed a progressive
      adjustment to T2, with no obvious discontinuities. In Experiment 2, probability
      of reinforcement was initially 20%, and the schedule switched to extinction after
      a varied number of trials were reinforced at the post-transition time. The number
      of post-transition reinforcements was used as independent variable. Behavior was
      examined in extinction to judge the state of temporal performance after a
      controlled amount of experience. Under these conditions, adjustment to T2 took
      place in two stages, and there was an intermediate phase when behavior changed
      little. These results are consistent with the hypotheses that animals
      continuously update the subjective probabilities that reinforcement comes at any
      given time and that responding occurs when the current estimate is above a
      certain threshold. We show that in spite of the continuous updating of time
      estimates, responding can show either continuous or discontinuous adjustments
      depending on the vicinity of the pre- and post-transition times and the
      probability of reinforcement. 

PMID- 24897536
TI  - Interval schedule performance in the goldfish Carassius auratus.
AB  - In experiment 1, five goldfish (Carassius auratus) paddle-pressed on fixed
      interval (FI) and variable-interval (VI) schedules for food pellet reinforcement.
      The order of conditions was FI 60 s, FI 240 s, FI 30 s, FI 60 s, and VI 60 s. FI
      responding showed a scalloped pattern and response-rate break points were
      proportional to interval duration. Post-food wait times varied with interval
      duration, but were not proportional. Response rate on VI was constant. Experiment
      2 studied the properties of food reinforcement as a time marker. The same five
      fish were presented an FI 60 s schedule of reinforcement with 25% of intervals
      ending in non-reinforcement (N). The fish responded faster and paused less
      following the omission stimulus (omission effect) and response rate was flat or
      declined through post-N intervals. 

PMID- 24897537
TI  - Effects of occasional short interfood intervals on temporal control in pigeons.
AB  - This study explored pigeon memory for short time intervals. Occasional (one per
      session) shorter-than-usual interfood intervals (IFIs) were interspersed in
      series of longer IFIs. In phase 1, the shorter IFIs were of a magnitude that
      varied from daily session to session. In phase 2, the shorter IFIs were of one
      magnitude for 20 consecutive daily sessions. Analysis of the results of both
      experiments showed that pigeons' memory for an IFI was not restricted to the
      immediately preceding interval but rather decayed exponentially with a half-life
      of around three intervals. This effect did not take time to develop and did not
      change over the course of training. These results have implications for the
      memory component of both clock and non-clock-based theories of animal timing. 

PMID- 24897540
TI  - CD86 +1057G/A polymorphism and risk of chronic immune thrombocytopenia.
AB  - The G to A transition at position +1057 single nucleotide polymorphism site in
      CD86 gene results in the alanine to threonine substitution, which further affects
      the antigen-presenting cells' signal transduction. Thus, the purpose of this
      study was to determine the association between CD86 +1057G/A polymorphism and the
      risk for chronic immune thrombocytopenia (cITP). The CD86 +1057G/A polymorphism
      in 158 cITP patients and 150 healthy controls were detected by polymerase chain
      reaction restriction fragment length polymorphism and then confirmed by DNA
      sequencing. In the patients with cITP, the frequencies of GG, AG and AA genotypes
      and G and A alleles were 18.4%, 58.8%, 22.8%, 47.8% and 52.2%, respectively. No
      difference in genotype and allele frequencies was detected in total cITP patients
      and normal controls (p = 0.913 and 0.845, respectively). Cases were subsequently
      classified by age at diagnosis, gender or clinical responses to glucocorticoids,
      and still no obvious discrepancy of genotype and allele frequencies was found
      between each of the groups and normal controls. In conclusion, this study
      suggests that CD86 +1057G/A polymorphism may be not associated with the genetic
      susceptibility to cITP in a Chinese population.

PMID- 24897538
TI  - Genes found essential in other mycoplasmas are dispensable in Mycoplasma bovis.
AB  - Mycoplasmas are regarded to be useful models for studying the minimum genetic
      complement required for independent survival of an organism. Mycoplasma bovis is
      a globally distributed pathogen causing pneumonia, mastitis, arthritis, otitis
      media and reproductive tract disease, and genome sequences of three strains, the
      type strain PG45 and two strains isolated in China, have been published. In this
      study, several Tn4001 based transposon constructs were generated and used to
      create a M. bovis PG45 insertional mutant library. Direct genome sequencing of
      319 independent insertions detected disruptions in 129 genes in M. bovis, 48 of
      which had homologues in Mycoplasma mycoides subspecies mycoides SC and 99 of
      which had homologues in Mycoplasma agalactiae. Sixteen genes found to be
      essential in previous studies on other mycoplasma species were found to be
      dispensable. Five of these genes have previously been predicted to be part of the
      core set of 153 essential genes in mycoplasmas. Thus this study has extended the
      list of non-essential genes of mycoplasmas from that previously generated by
      studies in other species. 

PMID- 24897542
TI  - TM4SF5 suppression disturbs integrin alpha5-related signalling and muscle
      development in zebrafish.
AB  - TM4SF5 (transmembrane 4 L six family member 5) is involved in EMT (epithelial
      mesenchymal transition) for liver fibrosis and cancer metastasis; however, the
      function(s) of TM4SF5 during embryogenesis remains unknown. In the present study
      the effects of TM4SF5 on embryogenesis of zebrafish were investigated. tm4sf5
      mRNA was expressed in the posterior somites during somitogenesis and in whole
      myotome 1 dpf (day post-fertilization). tm4sf5 suppression impaired development
      of the trunk with aberrant morphology of muscle fibres and altered expression of
      integrin alpha5. The arrangement and adhesion of muscle cells were abnormally
      disorganized in tm4sf5 morphants with reduced muscle fibre masses, where integrin
      alpha5-related signalling molecules, including fibronectin, FAK (focal adhesion
      kinase), vinculin and actin were aberrantly localized, compared with those in
      control fish. Aberrant muscle developments in tm4sf5 morphants were recovered by
      additional tm4sf5 or integrin alpha5 mRNA injection. Such a role for TM4SF5 was
      observed in the differentiation of C2C12 mouse myoblast cells to multinuclear
      muscle cells. Taken together, the results show that TM4SF5 controls muscle
      differentiation via co-operation with integrin alpha5-related signalling. 

PMID- 24897544
TI  - Scopolamine effects on juvenile conspecific recognition in rats: Possible
      interaction with olfactory sensitivity.
AB  - The social recognition of a juvenile conspecific by an adult male rat was
      evaluated as the decrease in investigation time when the same juvenile individual
      was reintroduced 30min after the first exposure period. The results showed that
      scopolamine impaired this transient individual recognition. A drop in
      investigation time was also observed in both tests (first and second exposure),
      with the same and with different juvenile individuals, in scopolamine treated
      animals. A second experiment showed that scopolamine disturbed the chemosensory
      preference for familiar odour observed in the control group. In the light of
      these two experiments, and according to the chemosensory mediation of social
      recognition in the rat, it is impossible to rule out a lack of odour
      discrimination in the absence of social recognition after scopolamine injection. 

PMID- 24897541
TI  - pSiM24 is a novel versatile gene expression vector for transient assays as well
      as stable expression of foreign genes in plants.
AB  - We have constructed a small and highly efficient binary Ti vector pSiM24 for
      plant transformation with maximum efficacy. In the pSiM24 vector, the size of the
      backbone of the early binary vector pKYLXM24 (GenBank Accession No. HM036220; a
      derivative of pKYLX71) was reduced from 12.8 kb to 7.1 kb. The binary vector
      pSiM24 is composed of the following genetic elements: left and right T-DNA
      borders, a modified full-length transcript promoter (M24) of Mirabilis mosaic
      virus with duplicated enhancer domains, three multiple cloning sites, a 3'rbcsE9
      terminator, replication functions for Escherichia coli (ColE1) and Agrobacterium
      tumefaciens (pRK2-OriV) and the replicase trfA gene, selectable marker genes for
      kanamycin resistance (nptII) and ampicillin resistance (bla). The pSiM24 plasmid
      offers a wide selection of cloning sites, high copy numbers in E. coli and a high
      cloning capacity for easily manipulating different genetic elements. It has been
      fully tested in transferring transgenes such as green fluorescent protein (GFP)
      and beta-glucuronidase (GUS) both transiently (agro-infiltration, protoplast
      electroporation and biolistic) and stably in plant systems (Arabidopsis and
      tobacco) using both agrobacterium-mediated transformation and biolistic
      procedures. Not only reporter genes, several other introduced genes were also
      effectively expressed using pSiM24 expression vector. Hence, the pSiM24 vector
      would be useful for various plant biotechnological applications. In addition, the
      pSiM24 plasmid can act as a platform for other applications, such as gene
      expression studies and different promoter expressional analyses. 

PMID- 24897543
TI  - High-density sodium and lithium ion battery anodes from banana peels.
AB  - Banana peel pseudographite (BPPG) offers superb dual functionality for sodium ion
      battery (NIB) and lithium ion battery (LIB) anodes. The materials possess low
      surface areas (19-217 m(2) g(-1)) and a relatively high electrode packing density
      (0.75 g cm(-3) vs ~1 g cm(-3) for graphite). Tested against Na, BPPG delivers a
      gravimetric (and volumetric) capacity of 355 mAh g(-1) (by active material ~700
      mAh cm(-3), by electrode volume ~270 mAh cm(-3)) after 10 cycles at 50 mA g(-1).
      A nearly flat ~200 mAh g(-1) plateau that is below 0.1 V and a minimal
      charge/discharge voltage hysteresis make BPPG a direct electrochemical analogue
      to graphite but with Na. A charge capacity of 221 mAh g(-1) at 500 mA g(-1) is
      degraded by 7% after 600 cycles, while a capacity of 336 mAh g(-1) at 100 mAg(-1)
      is degraded by 11% after 300 cycles, in both cases with ~100% cycling Coulombic
      efficiency. For LIB applications BPPG offers a gravimetric (volumetric) capacity
      of 1090 mAh g(-1) (by material ~2200 mAh cm(-3), by electrode ~900 mAh cm(-3)) at
      50 mA g(-1). The reason that BPPG works so well for both NIBs and LIBs is that it
      uniquely contains three essential features: (a) dilated intergraphene spacing for
      Na intercalation at low voltages; (b) highly accessible near-surface nanopores
      for Li metal filling at low voltages; and (c) substantial defect content in the
      graphene planes for Li adsorption at higher voltages. The <0.1 V charge storage
      mechanism is fundamentally different for Na versus for Li. A combination of XRD
      and XPS demonstrates highly reversible Na intercalation rather than metal
      underpotential deposition. By contrast, the same analysis proves the presence of
      metallic Li in the pores, with intercalation being much less pronounced. 

PMID- 24897545
TI  - Sex differences in food hoarding behaviour of Long Evans rats.
AB  - Food hoarding was examined in male and female Long Evans rats. During a three
      week period the animals were regularly submitted to the testing procedures, with
      food pellets in the home cage being either unrestricted (first week), or
      restricted (second and third week). When food pellets were present ad libitum,
      the hoarding scores were low, lower in females than in males. When food
      deprivation was imposed (second week), the animals responded by hoarding more
      pellets. This increase was more pronounced in males than in females. During the
      third week the hoarding scores became more or less stable, with males hoarding
      significantly more pellets than females. 

PMID- 24897546
TI  - Representation of conspecific song by chickadees: Comparisons among embedded 'fee
      bees'.
AB  - Captive black-capped chickadees (Parus atricapillus) were presented with normal
      (2-note) and lengthened (3-note) songs to investigate how note number and order
      are represented. Normal fee bee (FB) song was embedded in four different 3-note
      sequences containing an additional fee (F) or bee (B). Latency to vocalize after
      playback varied with the position, but not the type of added note, (i.e. slower
      responses to BFB and FFB than to FBF and FBB). Latency did not differ appreciably
      between normal (2-note) and these 3-note songs. The presence of normal 2-note
      song in each 3-note song may override note count. Our results provide further
      evidence that chickadees represent the absolute temporal location of the first,
      but not the last note of conspecific song. 

PMID- 24897547
TI  - Playful behaviour of piglets.
AB  - Domestic piglets living in multi-litter groups with their dams and other pigs in
      a large, socially and ecologically rich outdoor enclosure were observed, to
      obtain a quantitative description of the frequencies and sequences of behaviour
      patterns performed during play. Focal animal sampling was used to collect data on
      the playful behaviour of 14 male and 21 female piglets from birth to 14 weeks of
      age. The "play markers" hop, scamper, pivot, toss head, shake object and carry
      object were used to identify playful behaviour sequences. The variety of
      different behaviour patterns performed in first order transitions with play
      markers was highest in the first 6 weeks and declined thereafter with increasing
      age. Behaviour patterns occurring in transitions with play markers significantly
      more often than expected included stand, walk, trot, gallop, freeze, shove and
      circle. The overall frequency of play markers was significantly affected by age,
      with a peak frequency occurring between 2 and 6 weeks of age. Male and female
      piglets performed play markers at similar rates. Results are discussed with
      reference to the welfare of piglets kept in housing systems which limit playful
      behaviour. 

PMID- 24897548
TI  - Stress during mother-infant separation in ranch mink.
AB  - Effects of different mother-infant separation procedures on experienced stress by
      adults and young were studied using changes in circulating eosinophil levels as a
      stress indicator. It was found that (1) the amount of stress experienced by the
      mothers increases with the age of the pups at separation, when separation occurs
      as 6-week-, 8-week-, and 10-week-old pups, (2) eosinophil levels of mink pups
      show an ontogenetic development which complicates interpretations of the levels
      in terms of experienced stress, and (3) complete separation from 6-week-, 8-week
      , or 10-week-old pups reduces experienced stress of the mothers more radically
      than simple physical separation involving removal of the pups to adjoining cages.

PMID- 24897549
TI  - Effects of intertrial reinforcers on rats' timing behavior.
AB  - Two experiments were conducted to assess the effects of non-contingent intertrial
      interval (ITI) reinforcers on rats' discrimination of duration. In the first
      experiment, rats' discrimination of a 2 vs. 8 s of light was significantly
      disrupted when reinforcers were presented in the ITI. Disruption was not
      different on short (2 s) and long (8 s) trials. The second experiment showed that
      this disruptive effect was not specific to trials preceded by ITI reinforcers;
      responding on empty ITI trials run in the same session as ITI-reinforcer trials
      was also disrupted. This disruption however was not as great as on the ITI
      reinforcer trials. The results of these experiments show that ITI reinforcers
      affect timing discriminations in much the same way they affect classical
      conditioning and delayed matching to sample. However, detailed examination of the
      results suggests that the deleterious effects of ITI reinforcers in these
      different paradigms might be produced by different rather than the same
      mechanism. The results also support the conclusion that pre-trial reinforcement
      "priming" produces disruption rather than facilitation in complex tasks. 

PMID- 24897550
TI  - Massed and spaced stimulus sequences in dimensional discrimination.
AB  - In two experiments, pigeons' responding to a visual flicker-rate continuum was
      established by a maintained generalization procedure. For both experiments,
      variable-interval reinforcement was available for responses during stimuli from
      one half of the stimulus continuum while responses during other stimuli were
      extinguished. The first experiment compared gradients of dimensional stimulus
      control produced by randomly presented positive and negative stimuli with
      gradients produced by massed positive and negative stimuli. The second experiment
      alternated the order of massed stimulus sequences. In both cases, massing of
      stimulus sequences diminished positive dimensional contrast effects, without
      seriously disturbing discrimination between positive and negative stimuli. The
      results indicate that stimulus sequences can have an important role in the
      production of dimensional contrast effects. 

PMID- 24897552
TI  - Microwave-assisted preparation of inorganic nanostructures in liquid phase.

PMID- 24897551
TI  - Obstructive sleep apnea and incident diabetes. A historical cohort study.
AB  - RATIONALE: Despite emerging evidence that obstructive sleep apnea (OSA) may cause
      metabolic disturbances independently of other known risk factors, it remains
      unclear whether OSA is associated with incident diabetes. OBJECTIVES: To evaluate
      whether risk of incident diabetes was related to the severity and physiologic
      consequences of OSA. METHODS: A historical cohort study was conducted using
      clinical and provincial health administrative data. All adults without previous
      diabetes referred with suspected OSA who underwent a diagnostic sleep study at
      St. Michael's Hospital (Toronto, Canada) between 1994 and 2010 were followed
      through health administrative data until May 2011 to examine the occurrence of
      diabetes. All OSA-related variables collected from the sleep study were examined
      as predictors in Cox regression models, controlling for sex, age, body mass
      index, smoking status, comorbidities, and income. MEASUREMENTS AND MAIN RESULTS:
      Over a median follow-up of 67 months, 1,017 (11.7%) of 8,678 patients developed
      diabetes, giving a cumulative incidence at 5 years of 9.1% (95% confidence
      interval, 8.4-9.8%). In fully adjusted models, patients with apnea-hypopnea index
      (AHI) greater than 30 had a 30% higher hazard of developing diabetes than those
      with AHI less than 5. Among other OSA-related variables, AHI in rapid eye
      movement sleep and time spent with oxygen saturation less than 90% were
      associated with incident diabetes, as were heart rate, neck circumference, and
      sleep time. CONCLUSIONS: Among people with OSA, and controlling for multiple
      confounders, initial OSA severity and its physiologic consequences predicted
      subsequent risk for incident diabetes.

PMID- 24897553
TI  - Effect of cobalt substitution on Li(3-2x)Co(x)N local structure: a XAS
      investigation.
AB  - The influence of cobalt substitution on the local structural changes around Co
      atoms in the layered lithium nitridocobaltates Li(3-2x)Co(x)N for 0.05 <= x <=
      0.44 is investigated using Co K-edge X-ray absorption spectroscopy (EXAFS and
      XANES). The Co-N bond length in Li(3-2x)Co(x)N compounds is obtained vs x by
      performing EXAFS fitting and found to be shorter (1.80 A) than for x = 0 (Li3N),
      and its value does not change with x. A comparison of EXAFS data with XRD results
      is discussed. We show that the continuous decrease of interlayer distance versus
      Co content (x), described from XRD data, accounts for an average of the Co-N and
      Li-N distances, weighted by the number of these bond lengths. In addition, the
      present work supports the proposal that the Li1b-N bonds contract with x due to a
      significant increase of Coulombic attractive forces locally induced by the
      progressive Li(+)/Co(2+) substitution. XRD studies suggested that divalent Co
      ions bond to two nitrogen in Li(3-2x)Co(x)N. Although additional works are still
      needed to prove its valence, the present XAFS findings complements the local
      structure found by XRD, in good accord with the electrochemical properties
      previously reported.

PMID- 24897554
TI  - Critical analysis of endocrine disruptive activity of triclosan and its relevance
      to human exposure through the use of personal care products.
AB  - This review examines the mammalian and human literature pertaining to the
      potential endocrine disruptive effects of triclosan (TCS). Dietary exposure to
      TCS consistently produces a dose-dependent decrease in serum thyroxine (T4) in
      rats without any consistent change in TSH or triiodothyronine (T3). Human studies
      reveal no evidence that the TCS exposure through personal care product use
      affects the thyroid system. TCS binds to both androgen and estrogen receptors in
      vitro with low affinity and evokes diverse responses (e.g., agonist, antagonist,
      or none) in steroid receptor transfected cell-based reporter assays. Two of three
      studies in rats have failed to show that TCS exposure suppresses male
      reproductive function in vivo. Three of four studies have failed to show that TCS
      possesses estrogenic (or uterotrophic) activity in rats. However, two studies
      reported that, while TCS lacks estrogenic activity, it can amplify the action of
      estrogen in vivo. The in vitro, in vivo, and epidemiologic studies reviewed
      herein show little evidence that TCS adversely affects gestation or postpartum
      development of offspring. Furthermore, previously reported toxicity testing in a
      variety of mammalian species shows little evidence that TCS adversely affects
      thyroid function, male and female reproductive function, gestation, or postpartum
      development of offspring. Finally, doses of TCS reported to produce
      hypothyroxinemia, and occasional effects on male and female reproduction,
      gestation, and offspring in animal studies are several orders of magnitude
      greater than the estimated exposure levels of TCS in humans. Overall, little
      evidence exists that TCS exposure through personal care product use presents a
      risk of endocrine disruptive adverse health effects in humans.

PMID- 24897555
TI  - Liposomal bortezomib nanoparticles via boronic ester prodrug formulation for
      improved therapeutic efficacy in vivo.
AB  - In this study, we describe the development of liposomal bortezomib nanoparticles,
      which was accomplished by synthesizing bortezomib prodrugs with reversible
      boronic ester bonds and then incorporating the resulting prodrugs into the
      nanoparticles via surface conjugation. Initially, several prodrug candidates were
      screened based upon boronic ester stability using isobutylboronic acid as a model
      boronic acid compound. The two most stable candidates were then selected to
      create surface conjugated bortezomib prodrugs on the liposomes. Our strategy
      yielded stable liposomal bortezomib nanoparticles with a narrow size range of 100
      nm and with high reproducibility. These liposomal bortezomib nanoparticles
      demonstrated significant proteasome inhibition and cytotoxicity against multiple
      myeloma cell lines in vitro and remarkable tumor growth inhibition with reduced
      systemic toxicity compared to free bortezomib in vivo. Taken together, this study
      demonstrates the incorporation of bortezomib into liposomal nanoparticles via
      reversible boronic ester bond formation to enhance the therapeutic index for
      improved patient outcome. 

PMID- 24897556
TI  - Xanthohumol, a prenylated chalcone from beer hops, acts as an alpha-glucosidase
      inhibitor in vitro.
AB  - Xanthohumol (XN) is a unique prenylated flavonoid in hops (Humulus lupulus L.)
      and beer. XN alleviates hyperglycemia and has potential usage in the treatment of
      type 2 diabetes. In the present study, a series of in vitro experiments were
      performed to investigate whether XN was an effective inhibitor of alpha
      glucosidase. The results showed that XN inhibited alpha-glucosidase in a
      reversible and noncompetitive manner, with an IC50 value of 8.8 MUM and that XN
      inhibited the release of glucose from the maltose in the apical side of the Caco
      2 cell monolayer. Fluorescence and circular dichroism spectra results indicated
      that XN directly bound to alpha-glucosidase and induced minor conformational
      changes of the enzyme. These results demonstrated that XN is a promising alpha
      glucosidase inhibitor, which therefore could be used as functional food to
      alleviate postprandial hyperglycemia and as a potential candidate for the
      development of an antidiabetic agent. 

PMID- 24897557
TI  - Lysozyme-directed synthesis of platinum nanoclusters as a mimic oxidase.
AB  - We present a simple, one-pot approach for synthesizing ultrafine platinum (Pt)
      nanoclusters (NCs) under alkaline conditions using lysozyme (Lys) as a template.
      From the analysis of the nanoclusters by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, Lys VI-stabilized Pt NCs
      majorly consisted of Pt4 clusters. The formation of Pt NCs was confirmed using X
      ray photoelectron spectroscopy and Fourier-transformed infrared spectroscopy. The
      maximal fluorescence of Pt NCs appears at 434 nm with a quantum yield of 0.08, a
      fluorescence lifetime of 3.0 ns, and excitation-dependent emission wavelength
      behavior. Pt NCs exhibit an intrinsic oxidase-like activity because Pt NCs can
      catalyze O2 oxidation of organic substrates through a four-electron reduction
      process. Compared with larger Pt nanoparticles, the Pt NCs produce substantially
      greater catalytic activity in the O2-mediated oxidation of 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid), 3,3',5,5'-tetramethylbenzidine, and
      dopamine. 

PMID- 24897558
TI  - Processing of above/below categorical spatial relations by baboons (Papiopapio).
AB  - Three video-formatted experiments investigated the categorization of 'above' and
      'below' spatial relations in baboons (Papio papio). Using an identity matching-to
      sample task, six baboons correctly matched line-dot stimuli based on the 'above'
      or 'below' location of the dot relative to the line (Experiment 1). Positive
      transfer of performance was then observed when the line-dot distance depicted in
      the sample stimulus differed from that of the two comparison stimuli (Experiment
      2). Using a go/nogo procedure, two baboons were further trained to discriminate
      whether a 'B' character was displayed 'above' or 'below' a '3' character
      (Experiment 3). After training, a positive transfer of performance was observed
      with the same type of stimuli depicted in different type fonts. Altogether, these
      results suggest that baboons may form conceptual representations of 'above' and
      'below' spatial relations, and categorize visual forms on that basis. 

PMID- 24897559
TI  - Stimulus comparison and stimulus association processes in the perceptual learning
      effect.
AB  - In four experiments rats were given preexposure to two flavoured fluids,
      presented simultaneously in separate bottles. A conditioned aversion was then
      established to one flavour and the generalization of this aversion to the other
      was tested. Experiments 1a and 1b demonstrated that, in contrast to the effect
      obtained when the two flavours are presented at separate times during
      preexposure, such preexposure enhances generalization. Experiments 2a and 2b
      examined the hypothesis that this enhanced generalization was a consequence of
      the formation of an excitatory association between the two flavours during
      preexposure. In these experiments, the preexposure phase was followed by a phase
      of training (in which each flavour was presented alone on separate occasions)
      designed to extinguish the postulated association. It was found, however, that
      the enhancement of generalization survived the introduction of this procedure.
      Implications for the perceptual learning effect (the observation that certain
      forms of preexposure can restrict generalization between preexposed stimuli) are
      discussed. 

PMID- 24897560
TI  - A new version of the Monty Hall Dilemma with unequal probabilities.
AB  - In the Monty Hall Dilemma (MHD), a contestant makes a guess as to which door
      conceals a prize. The host then reveals the contents of an unchosen, incorrect
      door, and then gives the contestant a choice of sticking with the initial guess
      or switching to the remaining door. Given certain crucial assumptions, the
      rational solution is to switch. In the present study, subjects played 60 trials
      of either a standard four-door MHD or a new version of the MHD with unequal
      probabilities. Each has a counterintuitive solution. Subjects showed a strong
      tendency to stick when they should switch. Some learning took place, but
      switching in the standard condition reached a plateau. The results indicate that
      the equal probability condition is more suitable for studying satisficing, while
      the unequal probability condition is better for studying insightful learning. 

PMID- 24897561
TI  - Further evidence that rats use ordinal timing in a daily time-place learning
      task.
AB  - Rats received morning, midday, and afternoon sessions each day in a chamber
      located in a room containing distal spatial cues. A lever was mounted on each of
      the four walls. The rats could work for food on a different lever during each of
      the three sessions. The rats were able to learn the location of food availability
      during morning, midday, and afternoon sessions. Results obtained after skipped
      morning, midday, and afternoon sessions support our contention that rats solve
      this time-place task using ordinal timing, or knowledge of the daily
      spatiotemporal sequence of food availability. However, during probe sessions when
      the predicted location of food availability based on ordinal information
      conflicted with the predictions based on other types of information, behavioural
      compromise was evident. It appears that rats use multiple types of information,
      one of which is ordinal timing, to track the location of food availability in the
      daily time-place task. 

PMID- 24897562
TI  - Consistency of individual differences in behaviour of the lion-headed cichlid,
      Steatocranus casuarius.
AB  - The development of individual differences in behaviour in a novel environment, in
      the presence of a strange fish and during aggressive interactions with a mirror
      image was studied in the lion-headed cichlid (Steatocranus casuarius, Teleostei,
      Cichlidae). No consistency in behaviour was found at 4-5.5 months of age.
      However, behaviours scored in situations involving a discrete source of stress (a
      strange fish or conspecific) become significantly consistent at the age of 12
      months. At 4-5.5 but not 12 months of age, larger individuals approached and
      attacked the strange fish significantly more than smaller ones. These patterns
      may be associated with development and integration of motivational systems and
      alternative coping strategies. 

PMID- 24897563
TI  - The barrier choice paradigm: haloperidol reduces sensitivity to reinforcement.
AB  - The standard choice situation was modified by placing a 76 cm high barrier
      between two levers. To travel between levers, rats had to climb the barrier. Four
      doses of haloperidol were assessed for effects on motor and motivational systems.
      The drug impeded the rats' ability to climb the barrier. Residence and travel
      times increased, and changeover rates decreased. Pressing the levers was not
      entirely suppressed by haloperidol. The slope of the matching law decreased with
      increasing doses of haloperidol, showing reductions in the rats' sensitivity to
      reinforcement. The notion that neuroleptics impair the initiation or execution of
      complex motor acts and disrupt food-locomotion activity, is supported by these
      results. 

PMID- 24897564
TI  - Stimulus congruence affects perceptual processes in a novel Go/Nogo conflict
      paradigm in rats.
AB  - The performance of freely moving rats (n=18) in a decision-making reaction time
      task was analyzed to provide data that can be compared with noise-compatibility
      paradigms previously obtained in humans. Rats were first trained in an auditory
      pitch discrimination task involving a Go/Nogo response choice. In a subsequent
      phase, the two tones used in the previous phase were simultaneously presented in
      different combinations from two locations. Only the presence of the correct tone
      from the correct location was predictive of the reward. The observed behavioral
      strategies suggest a competition between two processes: one involving stimulus
      evaluation, response preparation and execution, the other involving recognition
      of the stimulus features associated with inhibition of the Go-response. The
      reaction times in the most adopted strategies towards the end of the experiment
      suggest an effect of stimulus congruence. Perceptual processes are affected by
      the congruence of 'pitch' and 'location' stimulus dimensions and the duration of
      the response may, but need not, be affected by overlapping dimensions. The
      analysis of error and aborted trials also suggest that subject's reaction and
      subsequent motor action may depend on whether stimulus identification processes
      can pass information to the response activation system prior to completion of
      sensory processing. The data are discussed in the framework of processing stages
      theory and dimensional overlap model. 

PMID- 24897565
TI  - The use of lectins as a non-invasive approach to the study of odour detection in
      mammals.
AB  - Olfaction is one of the most important sensory systems for many mammalian
      species. Yet, the extent to which olfactory stimuli control the behaviour of a
      specific species is difficult to establish. Traditionally, massive invasive
      techniques like destruction of the olfactory sensory epithelium or bulbectomy are
      applied to estimate the effect of olfactory stimuli. However, for behavioural
      research less invasive methods are required. Application of lectins to the
      olfactory epithelium seems to be a promising new approach to study the releasing
      effect of odours on behaviour. This new approach is demonstrated in 30 adult male
      Wistar rats for the lectins Concanavalin A, lotus tetragonolobus and wheat germ
      agglutinin. Rats were trained to detect low concentrations of ethyl acetate, 1
      methyl naphthalene or methacrylic acid. The lectins applied to the olfactory
      mucosa had selective inhibitory effects on odour detection; in each case
      detection inhibition was reversible within 4-48 h after lectin application. These
      results provide behavioural evidence for odour-specific inhibition without
      destruction to the animal. This new approach is discussed with the traditional
      invasive techniques use to inhibit odour detection. 

PMID- 24897566
TI  - Discriminative responsiveness by lambs to visual images of conspecifics.
AB  - A series of experiments was conducted to assess whether lambs are
      discriminatively responsive to visual images of conspecifics. Lambs (3-4-week
      old) consistently responded with more interest and less avoidance when exposed to
      a life-like image of an unfamiliar lamb, a ewe or the silhouette of a ewe, than
      to a meaningless mosaic of the same conspecific stimulus. In each instance, lambs
      preferentially sniffed the head region of the conspecific image. Slides of a ewe
      and a dog likewise elicited differential responses by lambs, but there were no
      clear differences in their attraction to, or avoidance of these two categories of
      stimuli. In contrast, adult ewes responded more negatively to the dog image than
      to the ewe slide. Overall, lambs appeared to respond to conspecific images as
      social stimuli, however, social discrimination by visual cues alone may improve
      with age and experience. 

PMID- 24897567
TI  - In silico veritas.
AB  - Innovations in computational nanoscience have traditionally come in conjunction
      with experimental innovations, but uncertainty often surrounds the
      trustworthiness of in silico studies. While the accuracy of simulations has been
      improving every year, considerably less attention has focused on dealing with
      increasing complexity, which may be the source of concern. Creating more
      realistic virtual experiments (without sacrificing theoretical and numerical
      accuracy) remains challenging, particularly when we are confronted with the
      polydispersivity characteristic of extra silico samples. Fortunately, there are
      various theoretical methods that can be used in conjunction with first-principles
      simulations, not the least of which are the statistical tools and techniques
      promised by the emerging fields of materials informatics and data-driven
      sciences.

PMID- 24897568
TI  - Improved catalytic activity and stability using mixed sulfonic acid- and hydroxy
      bearing polymer brushes in microreactors.
AB  - Sulfonic acid-bearing polymer brushes were grown on the inner walls of continuous
      flow glass microreactors and used in the acid-catalyzed hydrolysis of
      benzaldehyde dimethyl acetal as a test reaction. Randomly 1:1 mixed polymer
      brushes of poly-3-sulfopropyl methacrylate (PSPM) and poly-2-hydroxyethyl
      methacrylate (PHEMA) showed a 6-fold increase of the TOF value compared to the
      solely PSPM-containing microreactor. This remarkable improvement is attributed to
      the cooperative stabilizing effect of proximal OH groups on the active sulfonic
      acid moieties within the brush architecture. In fact, the rational mixing of SPM
      with methyl methacrylate (MMA) as an OH-free comonomer caused a drop in the
      activity of the resulting catalytic platform. A 5-fold increase of the TON of the
      1:1 PSPM-PHEMA versus the PSPM homopolymer brush systems additionally
      demonstrates the substantial increase in the stability of the mixed brushes
      catalytic platform, which could be continuously run over 7 days without
      significant loss of activity. The 1:1 PSPM-PHEMA mixed brush catalytic system
      also showed a good activity in the deprotection of 2-benzyl tetrahydropyranyl
      ether. 

PMID- 24897569
TI  - Open-field behaviour in chickens: A replication revisited.
AB  - In an attempt to show that the open field can still be used as a valid measure of
      fear, Jones (1983) has reported a failure to replicate some of our findings. The
      present studies show that this was due to procedural and methodological
      differences. For instance, we found that birds tested in a novel environment
      behaved quite differently from those, as in Jones' case, which were placed in one
      resembling the home cage. Moreover, birds housed in isolation for two days prior
      to testing reacted differently than those, as again in Jones' case, which were
      reared in isolation from hatching to the time of testing. The results were
      interpreted as being consistent with our view that open-field behaviour reflects
      a conflict between the need to reinstate contact with conspecifics on the one
      hand, and evade predation on the other. 

PMID- 24897570
TI  - Ethological analyses of the effects of naloxone and the opiate antagonist ICI
      154, 129 on social interactions in male house mice.
AB  - The influences of the mu blocker naloxone and the novel opioid delta receptor
      antagonist ICI, 154, 129 on videotaped encounters between individually-housed,
      male Swiss mice and anosmic male 'standard opponents' were assessed using a
      variety of ethological analyses. The effects of drugs were studied on individual
      elements and on the times allocated by subjects to broad categories of behaviour.
      Neither of the drugs significantly altered times allocated to broad categories of
      behaviour. Both doses of both compounds significantly increased the incidences of
      some 'fearful'/defensive postures. A more detailed analysis considered the
      effects of the drugs on the sequences of postures used in the resident's
      behaviour. This involved the generation of 'dendrograms' which provided support
      for the view that both naloxone and ICI 154, 129 altered the associations between
      behavioural elements seen in saline controls (especially at higher doses) and
      that the effects of these antagonists were qualitatively different. 

PMID- 24897571
TI  - The effect of food deprivation on self-control.
AB  - Two experiments examined the effect of food deprivation on choice in a discrete
      trials self-control paradigm, choice between a larger, more-delayed reinforcer
      and a smaller, less-delayed reinforcer. In Experiment 1, four pigeons were each
      deprived to 65%, 80%, and 90% of their free-feeding weights, and the delay to the
      smaller reinforcer was varied. Deprivation level did not affect choice, but the
      rate of ineffective key pecks made during the reinforcer delays increased as
      deprivation increased. In Experiment 2, four pigeons were exposed to conditions
      in which they were fed up to their 80% free-feeding weights following
      experimental sessions, and in which they were given no postsession feedings. Both
      the pigeons' weights and their latencies to insert their heads into the food
      hopper when food was available were lower when the pigeons were not fed following
      experimental sessions. Choice showed no change. Deprivation level affects
      response rate and eating behavior in these procedures, but not choice. 

PMID- 24897572
TI  - Directed song of male zebra finches as a predictor of subsequent intra- and
      interspecific social behaviour and pair formation.
AB  - Zebra finch males may, depending on early experience with con-specifics and/or
      with Bengalese finches, develop a preference for either conspecific or Bengalese
      finch females. This preference is usually measured in choice tests, using
      directed song of the males as a criterion. So far, experiments are lacking on
      whether preferences measured in this way are indicative of social and aggressive
      behaviour and pair formation when zebra finch males are given the opportunity to
      show these behaviour patterns. Therefore, the preference of 19 males was first
      measured in choice tests. Thereafter the males were placed individually in a cage
      with one zebra finch and one Bengalese finch female and observations on social
      behaviour were made (free choice experiments). There appeared to be a clear
      relationship between the preference as measured in the choice tests and both the
      later orientation of social behaviour to the two females, as well as pair
      formation shown in the free choice experiment. Directed song during choice tests
      therefore is a useful predictor of other social behaviour and of pair formation. 

PMID- 24897573
TI  - Ethological and physiological changes occuring in workers of Myrmica rubra L.
      maintained without queens.
AB  - Our research on queens of Myrmica rubra L. leads us to consider whether workers,
      having lived with their queens during the first months of their life, can
      remember the information acquired even if later deprived of queens or whether
      they need frequent contacts with their queens in order to remember those queens'
      characteristics. It appeared that workers one or two years old and maintained
      without queens during 2 to 5 months, always recognized those queens when newly
      encountering them. These experiments enabled us to reveal an unknown phenomenon.
      A few weeks after the queens were removed from experimental nests, the workers'
      aggregative reaction around those queens appeared to decrease, then, 2 to 4 weeks
      later, to reach again a normal level. These ethological variations occured
      together with physiological changes affecting the workers. At first, nearly all
      the workers presented an ovary development, then, a few which stayed inside the
      nest appeared to possess yet more developed ovaries, while the workers going
      readily out of the nest presented only weak or no ovary activity. This social
      regulation probably contributed to the survival of the society. 

PMID- 24897574
TI  - Functional hemidecortication by spreading depression or by focal epileptic
      discharge disrupts spatial memory in rats.
AB  - The importance of neocortex for the acquisition and retrieval of the water tank
      navigation task has been examined in 110 hooded rats. The animals were trained to
      swim to a small (10 cm in diameter) submersed platform 1 cm below the surface of
      a large pool (120 cm in diameter) of opaque water. In Experiment 1, naive rats
      with unilateral cortical spreading depression (SD) elicited by application of a
      filter paper soaked with 25% KC1 on one hemicortex were unable to find the
      platform during 1 min in about 50% of the 12 acquisition trials. The performance
      of functionally hemidecorticated rats did not improve after a single trial with
      the intact brain, but escape latencies were significantly shortened in rats given
      2,6 or 60 pretraining trials with intact brain. Even in the overtrained rats
      escape latencies under unilateral SD were significantly longer (14 sec) than in
      intact rats after 12 acquisition trials (5 sec). In Experiment 2, development of
      an epileptic focus established by local penicillin application onto the exposed
      cortical surface was electrophysiologically monitored. Regular interictal
      discharge (0.2 to 0.5 Hz) disrupted acquisition of the navigation task and
      interfered to a lesser degree with performance in rats given 12 and 36
      pretraining trials with the intact brain. The occipital foci were more disruptive
      than the frontoparietal ones. Performance recovered with cessation of the
      epileptic discharge. It is concluded that spatial memory mediating navigation in
      the water tank task requires coordinated activity of both cerebral hemispheres. 

PMID- 24897575
TI  - A further study of choice and percentage reinforcement.
AB  - In Experiment I four pigeons were trained in a concurrent chains procedure with
      fixed-ratio schedules (FR1) in the initial components and fixed-time schedules in
      the terminal components. Pecking one of the keys when both keys were white
      initiated a fixed time schedule on that key. A peck to the left key produced
      three stripes on the key. At the termination of the fixed-time component food
      always occurred. Pecking the other key produced either a circle or a triangle. If
      a circle appeared, reinforcement occurred. If a triangle appeared a brief timeout
      was given. Initially the stripes appeared on the left key and the circle and
      triangle on the left. This was reversed during the course of the experiment. In
      addition, sessions were conducted in which both circle and triangle sometimes
      preceded reinforcement and sometimes timeout. For most birds under most
      conditions there was a preference for the key that produced the circle and
      triangle. When these were uncorrelated with reinforcement and time out three of
      the birds preferred the key producing 100% reinforcement. In Experiment II three
      factors were varied and VI 20 sec schedules were used in the initial links
      instead of FR1. The results showed that pigeons preferred the 50% condition more
      1) the greater the duration of the terminal links, 2) the smaller the value on
      the initial link VI schedules and 3) the less the probability of food in the
      terminal link with stripes on the key. 

PMID- 24897576
TI  - Effects of social isolation on aggressiveness in fish with special reference to
      the swordtail (Xiphophorus helleri).
AB  - The attack readiness of socially isolated male swordtails (Xiphophorus helleri )
      was measured in two different aggression tests: (a) In the standard-opponent test
      the aggressive responses to a small, rather passive opponent swimming in a small
      adjacent compartment of the test aquarium were counted. (b) In the mirror test
      the subjects were confronted with their own mirror image. Social isolation for 4
      weeks resulted in a decrease of attack readiness in both test situations. It is
      concluded that -- similar to cichlids -- external stimuli from conspecifics are
      essential for maintaining the level of aggression readiness characteristic for
      socially living males. There are good reasons to propose that the effect of
      external stimuli is mediated by the pituitary-gonadal axis. On the other hand, it
      is well known from previous studies that, in escalated encounters between freely
      swimming males, isolated males fight longer and at higher intensities for rank
      order position than non-isolated males. The hypothesis is proposed that the high
      fighting intensity of previously isolated males could be due to an experience
      levelling effect of social isolation, i.e. the influence of different agonistic
      experience is reduced by isolation. A critical review of the literature on
      isolation-induced decremental and incremental effects on aggression in teleosts
      is presented. Often it is extremely difficult to compare the results of different
      authors because the methods of behavioural measurement differ to a large extent.
      However, it is a striking fact that social isolation of immature fish in all
      known cases has resulted in an increase of aggressiveness. Probably in mature
      males, depending on species and circumstances, either an incremental or a
      decremental effect of social isolation may be adaptive. On the one hand, a
      spontaneous increase of attack readiness may be advantageous for defence of a
      territory or a position in the social hierarchy and improves the ability of a
      single individual to join a group of strange conspecifics. On the other hand, it
      may be economic to lower the level of androgenic hormones to some extent in the
      absence of conspecifics, and this could lead to a reduction of the aggression
      level. 

PMID- 24897577
TI  - Naloxone does not affect tube restraint-induced target biting by male Swiss mice.
AB  - Opioid peptides have been implicated in the mediation of intermale conflict. The
      effect of naloxone upon tube restraint-induced target biting was investigated
      since a high correlation between bite scores and intermale aggression has been
      claimed. No significant modification of target biting behaviour by naloxone was
      produced, in mice either naive or habituated to the apparatus (high and low
      baselines of responding respectively) suggesting no involvement of opioid
      peptides in this paradigm. The results are discussed in terms of controllability
      of the presumably stressful situation and the relation of restraint-induced
      biting to conspecific aggression. 

PMID- 24897584
TI  - A facile BPO-mediated ortho-hydroxylation and benzoylation of N-alkyl anilines
      for synthesis of 2-benzamidophenols.
AB  - A facile benzoyl peroxide (BPO) mediated ortho-hydroxylation and benzoylation of
      N-alkyl anilines for the synthesis of 2-benzamidophenols has been developed. The
      reaction tolerates a wide range of functional groups and is a good method for the
      straightforward synthesis of valuable 2-benzamidophenols in good yields under
      mild conditions. 

PMID- 24897585
TI  - Learned orientation in landward swimming in the cricket Pteronemobius Lineolatus.
AB  - Pteronemobius lineolatus swims landward visually guided by terrestrial and, at
      times, associated celestial cues. Crickets irrespective of their previous visual
      experience swim towards artificial black horizontal landmarks. Non shore-dwelling
      crickets select random directions when released, under blue sky, for the first
      time on water surface in the absence of landmarks. If old enough to swim larvae
      and adult crickets learn a compass direction, during their first swim and each
      new directional landward swimming, if there are conspicuous terrestrial
      landmarks. There is forgetting and relearning of celestial compass orientation. 

PMID- 24897586
TI  - Grooming in the veery and the American robin: Evidence for a simple timing
      hierarchy.
AB  - Grooming behaviours in the veery (Catharus fuscescens ) and the American robin
      (Turdus migratorius ) cluster into four hierarchical groups based on function and
      anatomy: (1) non-preening, (2) upper body and wing preening, (3) lower body
      cleaning, and (4) tail preening in the veery; (1) non-preening, (2) body
      preening, (3) wing preening and (4) tail preening in the robin. The frequency
      distributions of the number of consecutive acts per cluster and the number of
      cluster visits per bout approximate geometric distributions in both species.
      These results provide evidence for the generality of the timing hierarchy model. 

PMID- 24897587
TI  - Postweaning environmental and social factors influencing the onset and expression
      of agonistic behavior in Norway rats.
AB  - Two studies were conducted to determine the importance of the postweaning
      environment and social milieu in regulating the expression of intraspecific
      aggression in Norway rats. In Experiment 1, male rats were housed either
      individually or in pairs at 21 days of age. In addition, one-half of the singly
      housed and paired animals were given experiences with intruders during
      maturation. At 85 days of age, all animals were given a brief intruder test and
      then removed from their postweaning environment and provided individually with
      homecages for a two week period until tested for aggression toward intruders.
      Results of intruder tests given during maturation indicated agonistic exchanges
      appeared earlier and more frequently in cages housing a single resident than
      cages with cohabiting males. However, agonistic exchanges between singly reared
      residents and intruders had detrimental consequences in adulthood especially
      under long-term combat situations. That is, although individually reared animals,
      with early fighting experiences, were capable of initiating intraspecific
      aggression, such individuals were unable to defend their homecage over a long
      period of time as evidenced by the high number of wounds and tendency to lose
      body weight during adult fighting. In Experiment 2, male Norway rats were reared
      in pairs from 21 days of age and identified as dominant or subordinate on the
      basis of intracolony social interactions shown during maturation. At 80 days of
      age, animals were paired with individually reared males in an unfamiliar cage for
      a 20 day period and examined for agonistic behavior toward intruders at 100 days
      of age. Group-reared subordinate males exhibited defensive behavior during
      confrontations with individually reared animals and incurred more wounds and lost
      more body weight than their cohabiting partner. In addition, subordinate males
      showed significantly fewer offensive postures toward intruders than individually
      reared cohabitants. In contrast, group-reared dominant animals did not differ
      from individually reared males in display of agonistic patterns, in number of
      wounds, and body weight changes during the period of cohabitation. These findings
      demonstrate that early rearing factors have pronounced effects on agonistic
      behavior. Animals experiencing defeat during development are more likely to lose
      agonistic confrontations in unfamiliar territory than either animals dominant in
      their early social interactions or animals without the experience of winning or
      losing agonistic encounters. These results have implications for the
      understanding of agonistic behavior and predicting outcomes of animal contests,
      and reveal important differences in agonistic experiences among animals reared in
      groups. 

PMID- 24897588
TI  - Responses of domestic chicks to novel food as a function of sex, strain and
      previous experience.
AB  - Food neophobia or a hesitancy to feed on unfamiliar food was examined in domestic
      chicks as a function of genetic and experiential factors associated with
      differential responsiveness to novelty. Chicks were presented with novel blue
      mash following a regime of food withdrawal and return. 'S' line chicks (light
      hybrid) fed significantly sooner, longer and more than did medium-hybrid 'T' line
      birds and females accepted novel food more readily than males. Food neophobia was
      significantly reduced by previous exposure to a variety of coloured foods and by
      enrichment of the home environment with assorted novel objects. The results are
      discussed in terms of the relationship between food neophobia, general
      responsiveness to novelty and underlying levels of fearfulness. 

PMID- 24897589
TI  - Simple and multiple schedule responding and behavioral contrast when pigeons
      press treadles.
AB  - Positive behavioral contrast has been observed when pigeons press treadles on
      multiple schedules for high rates of reinforcement, but not for low rates.
      Negative treadle-press contrast has been observed for low rates of reinforcement.
      Two experiments showed that differences between response rates emitted during
      simple and multiple schedules appear and fail to appear under similar conditions.
      The experiments showed that the rate of pressing during the less favorable
      component of a multiple schedule was less than the rate of pressing during a
      comparable simple schedule (negative contrast). The rate of treadle-pressing
      during the more favorable component was not greater than the rate of pressing
      during a comparable simple schedule, when the schedules provided a low rate of
      reinforcement (absence of positive contrast), but it was when the schedules
      provided a high rate of reinforcement (positive contrast). These results help to
      clarify the definition of behavioral contrast by showing that simple schedules
      may be appropriate baselines from which to define and measure contrast. 

PMID- 24897590
TI  - Some factors affecting pigeons' visual tracking behavior.
AB  - A novel delayed conditional discrimination procedure was used successfully to
      investigate some factors affecting pigeons' tracking of visual stimuli. Trials
      began with the brief illumination of one of the keys (randomly selected) from the
      left- or right-hand column of a three by three matrix of pecking keys. Then the
      next key in the same row was briefly lit. Finally, the remaining key in the row
      was lit along with one (randomly chosen) of the remaining five keys from the left
      or right-hand columns. A peck to the former but not the latter key was
      designated as correct and was rewarded. In Experiment 1 pigeons made correct
      choices on between 70 and 80 percent of trials, thereby demonstrating an ability
      to visually track objects. In Experiment 2 tracking accuracy was: a) reduced when
      either the first or second key in the sequence was omitted, b) improved when the
      sequence was repeated three times, c) reduced when duration of key illumination
      was reduced, and d) reduced by delays imposed between keys early but not late in
      the sequence. It was also found that tracking of vertical and horizontal
      sequences was approximately equal. 

PMID- 24897598
TI  - Identification and functional validation of RAD23B as a potential protein in
      human breast cancer progression.
AB  - Identification of protein targets that play a role in breast cancer invasion may
      help to understand the rapid progression of cancer and may lead to the
      development of new biomarkers for the disease. In this study, we compared two
      highly invasive and two poorly invasive breast cancer cell lines using
      comparative label-free LC-MS profiling in order to identify differentially
      expressed proteins that may be linked to the invasive phenotype in vitro. Forty
      five proteins were found to be upregulated, and 34 proteins, downregulated. UV
      excision repair protein RAD23 homologue B (RAD23B) was found among the
      downregulated proteins in highly invasive breast cancer cell lines. In poorly
      invasive breast cancer cell lines, siRNA-mediated downregulation of RAD23B
      subsequently led to an increase in invasion and adhesion in vitro.
      Immunohistochemistry analysis of 164 specimens of invasive breast cancer showed
      that having a high percentage (>80%) of RAD23B positive nuclei was significantly
      associated with histopathological grades 1 and 2 breast cancer and with low
      mitotic activity. In addition, a high staining intensity for RAD23B in the
      cytoplasm was significantly associated with histopathological grade 3 breast
      cancer. This study suggests a potential role of RAD23B in breast cancer
      progression and may further imply a tumor suppressor role of nuclear RAD23B in
      breast cancer. 

PMID- 24897600
TI  - Effects of aging on habituation in the nematode Caenorhabditis elegans.
AB  - The effects of aging on spontaneous locomotor behavior and habituation in a
      mechanosensory reflex were examined in the nematode Caenorhabditis elegans. Worms
      were tested at 4 days (at the peak of egg laying), at 7 days (when egg laying
      ends) and at 12 days post-hatching. Both spontaneous and reflexive movements were
      smaller in older worms than in younger worms. In addition the magnitude of these
      movements was related to life span; the shorter an animal's life span, the
      smaller its reversal movements while still young. Worms at all ages expressed
      habituation and dishabituation at a 10 s interstimulus interval (ISI); thus even
      aged worms were capable of non-associative learning. However, older worms showed
      greater habituation than did 4-day-old worms to stimuli delivered at a 60 s ISI.
      There was also an age-related change in the recovery from habituation. At days 4
      and 7, worms had recovered from habituation by 30 min after training; However,
      responses of day 12 worms were still significantly smaller than baseline at 30
      min after training. Further behavioral tests with normal and mutant worms may
      help elucidate the nature of the age-related changes in the learning and memory
      processes of C. elegans and the genetic mechanisms which underlie them. 

PMID- 24897599
TI  - Increased aggressiveness after brief social isolation of adult fish: a
      connectionist model which organizes this literature.
AB  - We examine the literature on fishes' aggressive behaviour after social isolation,
      in the light of a connectionist adaptive control system model for robot
      motivation and learning. If animals used the model's motivation modules, then
      social isolation would cause two simultaneous processes to occur-one
      progressively increasing motivation, the other decreasing display readiness. The
      readiness decrement would have the temporal flexibility typical of motivation
      changes, and would disappear soon after social stimuli reappeared. The
      incremental effect would be synaptic, and would be temporally more stable. Due to
      this stability difference, brief post-isolation aggression tests would tend to
      show that social isolates have depressed attack readiness, but longer tests would
      uncover the underlying increase in aggressiveness. In reviewing the literature,
      we find that this has been overwhelmingly the case. A new hypothesis about the
      adaptive value of the increase of aggression during isolation is outlined, which
      may help make the phenomenon more understandable. 

PMID- 24897597
TI  - Retinal function and morphology in the rabbit eye after intravitreal injection of
      the TNF alpha inhibitor adalimumab.
AB  - AIM: To study the effects of the tumor necrosis factor alpha inhibitor adalimumab
      on rabbit retina after injection into the vitreous body. METHODS: Forty-eight
      rabbits of mixed strain (9-12 months old, weighing ~ 3.5 kg) were randomized into
      four groups. Adalimumab was injected at one of two concentrations (1.25 mg or 2.5
      mg) into the eyes of two groups, and balanced salt solution into the eyes of the
      third group. The fourth group acted as controls. Full-field electroretinography
      (ffERG) was performed before injection and 1 and 6 weeks post-injection. At 6
      weeks post-injection the rabbits were euthanized and the sectioned retinas were
      studied. Retinal histology was studied with hematoxylin-eosin staining.
      Immunohistochemical analysis was performed on rods, cones, rod bipolar cells,
      horizontal cells, amacrine cells and Muller cells. RESULTS: No significant
      difference in ffERG amplitudes or implicit times was observed between the four
      groups at any time point. Histological and immunohistochemical findings were
      similar in all groups. CONCLUSIONS: Injection of adalimumab into the vitreous
      body of healthy rabbits, at doses up to 2.5 mg, does not appear to be toxic to
      the rabbit retina.

PMID- 24897601
TI  - Slides of conspecifics as representatives of real animals in laying hens (Gallus
      domesticus).
AB  - Four 18-week-old Ross Brown laying hens were trained to discriminate between
      slides of the heads of familiar or unfamiliar conspecifics. Those individuals
      trained to discriminate between slides of familiar conspecifics failed to show a
      better discrimination ability when presented with slides of novel views of these
      object birds, as compared with subjects trained to discriminate between slides of
      unfamiliar conspecifics and presented with similar corresponding novel views.
      There was also no evidence that subjects learnt to discriminate slides of
      familiar conspecifics more quickly than slides of unfamiliar conspecifics. It was
      concluded that there was no evidence that the hens perceived the slides presented
      as representations of their group members. 

PMID- 24897602
TI  - Social constraints determine what is learned in the chimpanzee.
AB  - A group of six chimpanzees was placed in a social learning situation, without
      training. The learning task was an operant conditioning situation; that is, a
      subject had to pull two handles simultaneously to cause a piece of fruit to fall
      into the cage. Only three individuals acquired the operant behaviour. For the
      operant individuals, social influences on the expression of the learning task
      were then examined; the dominant chimpanzee during feeding had an inhibiting
      effect when close to the operant subjects. Depending on the subject, social
      factors may influence not only the specific expression of what is learnt, but
      also the nature of what is learnt. Chimpanzees appear to experience situations
      differently: they develop an individual problem-solving strategy according to
      their social relationships even if the experimental procedure is the same for
      all. 

PMID- 24897603
TI  - Lateral forebrain lesions affect pecking accuracy in the pigeon.
AB  - Pigeons were trained to preferentially peck the centermost element of a
      concentric key array. When they had learned the task to a criterion the subjects
      received lesions of the lateral telencephalon. The ablation caused an unexpected
      performance improvement, proportionally more pecks being directed at the central
      key element. However, on closer analysis this result was interpreted as being the
      effect of a mandibular gape control loss rather than being due to an actual peck
      localization enhancement. 

PMID- 24897604
TI  - Foraging wood-ants Formica aquilonia yarrow (hymenoptera: formicidae) tend to
      adopt the ideal free distribution.
AB  - Three colonies of red wood-ants were established in the laboratory; each colony
      was provided with two feeding sites, each one metre from the nest. An aqueous
      solution of sucrose (7% w/v) was pumped at a defined rate to each site, where it
      dropped on filter paper for collection by foraging ants. The distribution of
      foragers between sites was compared daily with the distribution of delivery rates
      of sucrose between sites. Ratios of delivery rates between sites were 1:1, 2:1,
      or 3:1; each distribution was maintained for eight days, and in the 2:1 and 3:1
      conditions the delivery rates were exchanged between sites after eight days so
      that the richer of a pair of sites was impoverished and the poorer was enriched.
      Foragers came to approximate the ideal free distribution within two or three days
      of an exchange of delivery rates; their distribution then remained stable until
      the next exchange of rates. The adoption of the ideal free distribution suggests
      that individual ants used movement rules which maintained the maximum possible
      rate of feeding: this behaviour would ensure that the foraging population as a
      whole maintained the fastest rate of intake of food possible from a given
      environment. 

PMID- 24897605
TI  - Possible function for a previously discovered pheromone on the last sternite of
      the ant Tetramorium impurum mayr (hymenoptera, formicidae, myrmicinae).
AB  - Experimental results show that, if laid together with a poison gland extract on
      artificial trails, the ethological factor previously found on the last visible
      sternite of Tetramorium impurum incites ants to prefer these trails to poison
      gland ones, as well as newer trails to older ones. It is demonstrated that the
      foragers effectively deposit onto the ground some factor acting synergistically
      with poison gland secretions as a trail pheromone. This factor, which may be the
      one under study, may incite ants to follow preferentially the newest trails
      traced on their foraging area. 

PMID- 24897606
TI  - Influence of motivational state on choice of food or a dustbathing/foraging
      substrate by domestic hens.
AB  - Domestic hens were trained to run a Y-maze and make an association between
      differently coloured doorways and access to food pellets or sand. The hens were
      tested for their choice of doorway when the goals were not visible from the
      choice point and when they were food or sand deprived. Hens made the choice
      appropriate to their deprivation state (correct choice) significantly more often
      for food than sand and were faster at choosing and entering the goal box when
      food deprived. In a follow up experiment, the goals were visible from the choice
      point. Again the hens chose correctly significantly more often when food than
      sand deprived and made the choice and entered the goal box faster when food
      deprived. Thus, failure to choose sand in the first experiment was not due to an
      inability to learn the association, but appears to result from a strong
      motivation to feed in the Y-maze, even when not food deprived, and a weak
      motivation to dustbathe or forage, even when sand deprived. 

PMID- 24897608
TI  - Different aggressive behaviours are exaggerated by facing vs. broadside
      subliminal stimuli shown to socially isolated Siamese fighting fish, Betta
      splendens.
AB  - We report and analyse some features of a new phenomenon: socially isolated Betta
      splendens become extremely hyper-aggressive after seeing brief glimpses of fish
      models or mirrors. These brief glimpses are below the threshold for releasing
      aggressive display, so they are considered subliminal aggressive stimuli. The
      hyper-aggressiveness was observed to last for weeks. To confirm that hyper
      aggressiveness was dependent upon the aggressive significance of the subliminal
      stimuli, we presented socially isolated Betta splendens with subliminal models in
      either a 'facing' posture (used mainly in aggressive contexts), or a 'broadside'
      posture (used in many social contexts). The fish shown the aggressive 'facing'
      subliminal stimuli became more aggressive, while those shown 'broadside' stimuli
      performed more generalized advertisement behaviours. The display posture of the
      model, which may incorporate specific features relevant to aggression, therefore
      determined how the subliminal aggressive stimuli altered subsequent
      aggressiveness. This difference was also persistent. Subliminal stimuli may thus
      be implicated in the hyper-aggressiveness so often reported after social
      isolation. 

PMID- 24897607
TI  - Optimal estimation for regression models on tau-year survival probability.
AB  - A logistic regression method can be applied to regressing the [Formula: see text]
      year survival probability to covariates, if there are no censored observations
      before time [Formula: see text]. But if some observations are incomplete due to
      censoring before time [Formula: see text], then the logistic regression cannot be
      applied. Jung (1996) proposed to modify the score function for logistic
      regression to accommodate the right-censored observations. His modified score
      function, motivated for a consistent estimation of regression parameters, becomes
      a regular logistic score function if no observations are censored before time
      [Formula: see text]. In this article, we propose a modification of Jung's
      estimating function for an optimal estimation for the regression parameters in
      addition to consistency. We prove that the optimal estimator is more efficient
      than Jung's estimator. This theoretical comparison is illustrated with a real
      example data analysis and simulations. 

PMID- 24897609
TI  - Peck orders and group size in laying hens: 'futures contracts' for non
      aggression.
AB  - We analyse a simple model of the establishment and maintenance of dominance
      hierarchies in hens. To be beneficial, dominance relationships require that the
      probability of meeting the same individual repeatedly is high, otherwise costs of
      establishing the dominance relation are never recouped. Winners and losers
      benefit from dominance relationships, not necessarily from changing the rate at
      which they acquire resources but by avoiding costly contests over them in future
      encounters. We show that so-called 'loser effects', in which animals base their
      strategies for contesting resources solely upon their past experiences of winning
      or losing dominance fights and not upon who their opponent is, cannot work -
      these strategies ('pragmatists') must additionally involve either individual or
      status category recognition. As alternatives to dominance relationships, we show
      that signals of status or fighting ability that determine access to contested
      resources are expected to evolve in species with typically large groups because
      in such conditions the costs of establishing dominance relations are not
      recouped. Such signals do not depend upon recognizing others individually, but
      rather upon general category recognition. Status signals are not expected in
      small groups because dominance relationships are likely to be cheaper and just as
      effective. The results of the model have implications for the welfare of hens
      kept in large groups. 

PMID- 24897610
TI  - Stability of dyadic dominance status and recognition of the opponent in male
      crickets Gryllus bimaculatus (Orthoptera: Gryllidae).
AB  - In dyads of adult male Gryllus bimaculatus, a dominance relationship is
      established at the first agonistic interaction between the two insects. The
      comparison of the aggressive behaviour displayed by adult males shows that field
      crickets act in an identical manner when confronted with an unfamiliar opponent
      or with one already encountered in a different environment. In contrast, analysis
      of five successive conflicts in a given environment shows that the dynamics of
      the interactions varies according to whether the opponents are always the same or
      one is changed at each encounter. The conflicts are solved more rapidly when the
      interactions involve the same opponents. 

PMID- 24897611
TI  - Artificial neural networks as a classification method in the behavioural
      sciences.
AB  - The classification and recognition of individual characteristics and behaviours
      constitute a preliminary step and is an important objective in the behavioural
      sciences. Current statistical methods do not always give satisfactory results. To
      improve performance in this area, we present a methodology based on one of the
      principles of artificial neural networks: the backpropagation gradient. After
      summarizing the theoretical construction of the model, we describe how to
      parameterize a neural network using the example of the individual recognition of
      vocalizations of four fallow deer (Dama dama). With 100% recognition and 90%
      prediction success, the results are very promising. 

PMID- 24897612
TI  - Decrease of response to social separation in preparturient ewes.
AB  - The response to social isolation was compared in multiparous non-pregnant
      (controls) and periparturient (experimental) Rambouillet ewes over three tests
      performed at times corresponding to 111+/-31 h prepartum (148 days of pregnancy),
      3.1+/-1.2 h prepartum (after onset of labour) and 1.3+/-0.2 h postpartum for the
      experimental group. Twenty-four and 15 ewes (test 1), 16 and 12 (test 2) and 7
      and 10 (test 3) were tested in control and experimental groups respectively. Each
      test lasted 10 min (5 min in presence of conspecifics, 5 min in their absence).
      High-pitched bleats, locomotor activity, attempts at jumping out of the testing
      pen, eliminations and latency out of the pen were recorded. In both groups and in
      all tests there was a significant increase of agitation following removal of the
      conspecifics. Few differences were encountered between groups in the first test.
      On the other hand, in the second and third tests the agitation induced by social
      separation was significantly higher in dry ewes for the great majority of
      behaviours. We conclude that the reduction of response to social separation
      previously reported in postparturient ewes is not totally due to the maternal
      bonding to the neonate, but that before parturition, some physiological factors
      internal to the mother already reduce gregariousness. 

PMID- 24897613
TI  - Concurrent schedule control of human observing during auditory vigilance.
AB  - Six adult humans experienced a vigilance task which required them to detect
      auditory signals and report their occurrence by pressing a button. A subject sat
      on a chair with his or her head between two small panels. When the subjects
      pressed his or her head against one of the panels, white noise was presented from
      a speaker set behind the panel. Signals for the left speaker were presented
      according to a variable-interval schedule and those for the right speaker were
      presented according to another variable-interval schedule (concurrent variable
      interval variable-interval schedule). All subjects showed systematic variations
      of time allocation, although slopes of choice proportions showed severe
      undermatching according to the generalized matching law. The remaining three
      subjects, who were first exposed to some concurrent schedules, also showed such a
      tendency. Then, they experienced a training in which they were exposed to each
      variable-interval schedule successively before being exposed to them
      concurrently. This procedure reduced the amount of undermatching. These findings
      were in good agreement with previous studies reporting conformity of human
      observing responses to the generalized matching law. 

PMID- 24897614
TI  - Behavioral contrast with changes in duration and rate of reinforcement.
AB  - Behavioral contrast can be defined as an inverse relation between rate of
      responding in one component of a multiple schedule and conditions of
      reinforcement in the other components. The present study was an attempt to
      produce contrast with changes in duration of reinforcement. Pigeons pecked a key
      for mixed grain delivered by a multiple variable-interval variable-interval
      schedule. In Experiment 1, the reinforcer duration in the second component was
      decreased or increased, for different subjects, by a factor of two, four, and six
      from that delivered during baseline. These changes usually produced contrast. In
      Experiment 2, rate, duration, or rate and duration of reinforcement varied in the
      second component. Contrast was usually observed when only one variable was
      manipulated. When both variables were manipulated in the same condition, but in
      opposite directions, responding in the constant component usually changed
      inversely with the change in rate of reinforcement, not the change in reinforcer
      duration. The results demonstrate that changes in duration of reinforcement can
      produce contrast. They also increase the empirical base for which a successful
      theoretical account of contrast must encompass and the generality of contrast,
      which increases its potential practical implications. 

PMID- 24897615
TI  - Food recruitment as a component of the trunk-trail foraging behaviour of Lasius
      fuliginosus (Hymenoptera: Formicidae).
AB  - Field investigations showed that the ant Lasius fuliginosus combines stable
      foraging behaviour based on long-term memory and spatial specialization with more
      flexible actions, based on food recruitment. The use of food recruitment varies
      according to the season and the type of food. Baits of meat or large prey
      elicited recruitment during the major part of the year, except in the autumn,
      while baits of sugar elicited recruitment only in early spring, before the aphid
      colonies developed. A permanent trunk trail was established after a recruitment
      towards a newly discovered and stable source of carbohydrate food. This happened
      in early spring when the food sources were scarce or when spring migrating aphids
      were produced. 

PMID- 24897616
TI  - Socialization processes in primates: use of multivariate analyses II-Influence of
      sex on social development of captive rhesus monkeys.
AB  - In a previous study, we demonstrated the importance of social interactions in the
      development of non-human primate infants. These results confirmed the social
      network concept. According to this concept, it is assumed that socialization
      processes would differ in various social environments. However, much variability
      remained to be explained. In the present study we investigated especially the
      influence of infants' gender on socialization processes. In relation to the
      previous results, the influence was tested within groups having the same social
      structure. At the Wisconsin Regional Primate Research Center, four mother-peer
      groups of rhesus macaques (Macaca mulatta) were studied. Therefore no adult male
      model was available to infants. Twenty infants, including eight males, eight
      females and four prenatally DES-treated females, were the subjects of this study.
      We considered six comprehensive developmental parameters to account for the two
      main socialization processses, the acquisition of the social behavioral
      repertoire and the establishment of a network of social relationships. We
      analyzed the variability of these parameters using a new multivariate technique
      previously described in a companion paper. This new technique is derived from the
      Principal Components Analysis and Multivariate Analyses of Variance. The model
      used in this analysis included two intrinsic features of infants, sex and age and
      two variables related to the social organization of the groups, mother's rank and
      social group. This 4-variable-model significantly accounted for most of the
      variability of the developmental parameters. The results showed that the social
      group and the infant's sex were the most influential variables when infants
      initiated interactions: male and DES female infants displayed a greater
      behavioral diversity than non-treated female infants. When infants were
      recipients in interactions, social organization variables (social group and
      mother's rank, respectively) had the greatest influence on the socialization
      processes while infants' gender was less influential. In this case the effect of
      sex was confounded with the social group effect; male infants then differed from
      both kind of female infants in being looked at more frequently, in being
      contacted by a larger variety of partners and in receiving a greater variety of
      social behaviors. This new example of applying multivariate methods to the study
      of individual social development confirms the potential of this method to provide
      new insights into behavioral development. 

PMID- 24897617
TI  - Learning about the opponent during aggressive encounters in paradise fish
      (Macropodus opercularis L.): when it takes place?
AB  - Dyadic encounters between paradise fish (Macropodus opercularis L.) males were
      staged. In a first experiment, the duration of the dominance-submissive phase
      (cohabitation following the end of fighting) and the inter-encounter interval
      were manipulated. Measuring the duration both of threatening, fighting, mouthlock
      and head-tail display it was found that the memory of an aggressive encounter
      largely disappeared after 6 days and the duration of the dominance-submissive
      experience had no effect on the stability of memory formation in this species. In
      a second experiment, one group of fighting fish were separated just after the end
      of the fight, while concomitantly fish still fighting were also separated. On the
      next day, the aggressive behaviour of these two groups was compared and found
      that fighting decreased only in the group, of which the members had been able to
      finish the encounter. Our results show that: (1) post-contest harassment of the
      submissive has little if any impact on the behaviour changes that result; (2) an
      aggressive encounter affects the duration and patterns of a subsequent fight only
      if the fight is completed (i.e. dominance relationship develop); and (3)
      regardless, of the previous experience memory will fade after 6 days. In
      conclusion, the experience of winning or losing is the promoter of behavioural
      changes that result from aggressive experience. It is suggested that the social
      behaviour of the paradise fish determines the constraints of memory and learning
      in aggressive situations. 

PMID- 24897618
TI  - Bone marrow cell therapies in ischemic cardiomyopathy.
AB  - Decrements in ventricular function due to the permanent loss of contractile
      tissue remain problematic in patients with ischemic cardiomyopathy. For this
      reason, cell replacement therapy has received much popularity in recent years.
      Bone marrow is an abundant and accessible source of stem cells with regenerative
      potential. However, ischemic heart disease clinical trials based on bone marrow
      derived stem cell (BMC) infusion have yielded discrepant results and marginal
      therapeutic benefits, making this modality's future uncertain. Further
      investigation of molecular and cellular characteristics critical for therapeutic
      efficacy and defining the mechanism(s) of BMC-mediated cardiac repair will be
      paramount for harnessing their full therapeutic potential. 

PMID- 24897619
TI  - Atomic force microscopy characterization and lithography of Cu-ligated
      mercaptoalkanoic acid "molecular ruler" multilayers.
AB  - Hybrid chemical patterning strategies that combine the sophistication of
      lithography with the intrinsic precision of molecular self-assembly are of broad
      interest for applications including nanoelectronics and bioactive surfaces. This
      approach is exemplified by the molecular-ruler process where the sequential
      deposition of mercaptoalkanoic acid molecules and coordinated metal ions is
      integrated with conventional lithographic techniques to fabricate registered,
      nanometer-scale spacings. Herein, we illustrate the capabilities of atomic force
      microscopy characterization and lithography to investigate the morphology,
      quality, and local thickness of Cu-ligated mercaptohexadecanoic acid multilayers
      on Au{111} substrates. These multilayers are a key component utilized in the
      molecular-ruler process. The rich and varied topographic features of each layer
      are investigated via contact-mode atomic force microscopy. Using nanoshaving, an
      atomic force microscopy lithographic strategy that reveals the underlying Au{111}
      substrate via tip-induced desorption of a molecular film, the local thicknesses
      of these multilayers are ascertained; these thicknesses are consistent with the
      anticipated heights for Cu-ligated mercaptohexadecanoic acid multilayers as well
      as previous ensemble surface analytical measurements. By regulating the force set
      point utilized during nanoshaving, the upper layer of a Cu-ligated
      mercaptohexadecanoic acid bilayer is removed, revealing the carboxyl moiety of
      the lower mercaptohexadecanoic acid layer. This selective nanoshaving
      demonstrates a simple and practical means to generate three-dimensional
      multilayers and to reveal buried chemical functionalities within metal-ligated
      multilayers. 

PMID- 24897620
TI  - Detailed microscopic unfolding pathways of an alpha-helix and a beta-hairpin:
      direct observation and molecular dynamics.
AB  - We present a combined experimental and computational study of unfolding pathways
      of a model 21-residue alpha-helical heteropeptide (W1H5-21) and a 16-residue beta
      hairpin (GB41-56). Experimentally, we measured fluorescence energy transfer
      efficiency as a function of temperature, employing natural tryptophans as donors
      and dansylated lysines as acceptors. Secondary structural analysis was performed
      with circular dichroism and Fourier transform infrared spectroscopy. Our studies
      present markedly different unfolding pathways of the two elementary secondary
      structural elements. During thermal denaturation, the helical peptide exhibits an
      initial decrease in length, followed by an increase, while the hairpin undergoes
      a systematic increase in length. In the complementary computational part of the
      project, we performed microsecond length replica-exchange molecular dynamics
      simulations of the peptides in explicit solvent, yielding a detailed microscopic
      picture of the unfolding processes. For the alpha-helical peptide, we found a
      large heterogeneous population of intermediates that are primarily frayed single
      helices or helix-turn-helix motifs. Unfolding starts at the termini and proceeds
      through a stable helical region in the interior of the peptide but shifted off
      center toward the C-terminus. The simulations explain the experimentally observed
      non-monotonic variation of helix length with temperature as due primarily to the
      presence of frayed-end single-helix intermediate structures. For the beta-hairpin
      peptide, our simulations indicate that folding is initiated at the turn, followed
      by formation of the hairpin in zipper-like fashion, with Calpha...Calpha contacts
      propagating from the turn to termini and hairpin hydrogen bonds forming in
      parallel with these contacts. In the early stages of hairpin formation, the
      hydrophobic side-chain contacts are only partly populated. Intermediate
      structures with low numbers of beta-hairpin hydrogen bonds have very low
      populations. This is in accord with the "broken zipper" model of Scheraga. The
      monotonic increase in length with temperature may be explained by the zipper-like
      breaking of the hairpin hydrogen bonds and backbone contacts. 

PMID- 24897621
TI  - Structural similarity based kriging for quantitative structure activity and
      property relationship modeling.
AB  - Structurally similar molecules tend to have similar properties, i.e. closer
      molecules in the molecular space are more likely to yield similar property values
      while distant molecules are more likely to yield different values. Based on this
      principle, we propose the use of a new method that takes into account the high
      dimensionality of the molecular space, predicting chemical, physical, or
      biological properties based on the most similar compounds with measured
      properties. This methodology uses ordinary kriging coupled with three different
      molecular similarity approaches (based on molecular descriptors, fingerprints,
      and atom matching) which creates an interpolation map over the molecular space
      that is capable of predicting properties/activities for diverse chemical data
      sets. The proposed method was tested in two data sets of diverse chemical
      compounds collected from the literature and preprocessed. One of the data sets
      contained dihydrofolate reductase inhibition activity data, and the second
      molecules for which aqueous solubility was known. The overall predictive results
      using kriging for both data sets comply with the results obtained in the
      literature using typical QSPR/QSAR approaches. However, the procedure did not
      involve any type of descriptor selection or even minimal information about each
      problem, suggesting that this approach is directly applicable to a large spectrum
      of problems in QSAR/QSPR. Furthermore, the predictive results improve
      significantly with the similarity threshold between the training and testing
      compounds, allowing the definition of a confidence threshold of similarity and
      error estimation for each case inferred. The use of kriging for interpolation
      over the molecular metric space is independent of the training data set size, and
      no reparametrizations are necessary when more compounds are added or removed from
      the set, and increasing the size of the database will consequentially improve the
      quality of the estimations. Finally it is shown that this model can be used for
      checking the consistency of measured data and for guiding an extension of the
      training set by determining the regions of the molecular space for which new
      experimental measurements could be used to maximize the model's predictive
      performance. 

PMID- 24897622
TI  - MUHigh resolution-magic-angle spinning NMR spectroscopy for metabolic phenotyping
      of Caenorhabditis elegans.
AB  - Analysis of model organisms, such as the submillimeter-size Caenorhabditis
      elegans, plays a central role in understanding biological functions across
      species and in characterizing phenotypes associated with genetic mutations. In
      recent years, metabolic phenotyping studies of C. elegans based on (1)H high
      resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR)
      spectroscopy have relied on the observation of large populations of nematodes,
      requiring labor-intensive sample preparation that considerably limits high
      throughput characterization of C. elegans. In this work, we open new platforms
      for metabolic phenotyping of C. elegans mutants. We determine rich metabolic
      profiles (31 metabolites identified) from samples of 12 individuals using a (1)H
      NMR microprobe featuring high-resolution magic-angle coil spinning (HR-MACS), a
      simple conversion of a standard HR-MAS probe to MUHR-MAS. In addition, we
      characterize the metabolic variations between two different strains of C. elegans
      (wild-type vs slcf-1 mutant). We also acquire a NMR spectrum of a single C.
      elegans worm at 23.5 T. This study represents the first example of a metabolomic
      investigation carried out on a small number of submillimeter-size organisms,
      demonstrating the potential of NMR microtechnologies for metabolomics screening
      of small model organisms. 

PMID- 24897623
TI  - Streamlining bottom-up protein identification based on selective ultraviolet
      photodissociation (UVPD) of chromophore-tagged histidine- and tyrosine-containing
      peptides.
AB  - We report a fast and highly efficient diazonium reaction that couples a
      nitroazobenzene chromophore to tyrosine and histidine residues, thus endowing
      peptides with high photoabsorption cross sections at 351 nm in the gas phase.
      Only the tagged peptides undergo ultraviolet photodissociation (UVPD) at 351 nm,
      as demonstrated for several Tyr- and His-containing peptides from protein
      digests. Additional selectivity is achieved by the integration of the UVPD-MS
      method with an in silico database search restricted to Tyr- and His-containing
      peptides. A modified MassMatrix algorithm condenses analysis by filtering the
      input database file to include Tyr/His-containing peptides only, thus reducing
      the search space and increasing confidence. In summary, derivatization of
      specific amino acid residues in conjunction with selective activation of the
      derivatized peptides provides a streamlined approach to shotgun proteomics. 

PMID- 24897625
TI  - Simultaneous processing of short delays and higher order temporal intervals
      within a session by pigeons.
AB  - This study tests the ability of pigeons to process simultaneously two kinds of
      temporal intervals of the sort relevant in foraging problems: delays within
      trials on the order of seconds as well as 'higher order' intervals, on the order
      of minutes, within the session. Pigeons were given 20 min sessions of a chained
      VI 5 s-FI 10 s schedule reinforcement. A particularly large reinforcer was
      delivered either after 16 min or after 6 min, in a blocked design. In probe
      sessions no large reinforcer was given. The rate of responding in probe sessions
      following training with the early reinforcer showed a peak in rate of responding
      at about 6 min. In probe sessions following training with the late reinforcer,
      the rate of responding showed only a linear increase. In addition, empty trials
      using the peak procedure showed that the pigeons timed the FI 10 s within trials,
      as predicted by models of timing with two accumulators. Baseline sessions with no
      large reinforcer at the beginning of the experiment showed a bitonic function
      with slight changes in rates of responding. 

PMID- 24897624
TI  - Impact of Cardiovascular Risk Factors on Long-Term Mortality After Liver
      Transplantation.
AB  - Immunosuppression with calcineurin inhibitors has contributed to an increased
      prevalence of hypertension, diabetes, and hypercholesterolemia in patients
      receiving liver transplantation. This study evaluated the prevalence of
      cardiovascular risk factors, their management, and long-term mortality after
      liver transplantation. Medical records were reviewed in 333 adult patients who
      underwent orthotopic liver transplantation. Data were collected on medical
      diagnoses before and after transplantation, medication use, and on long-term
      mortality. The 333 patients in the study included 223 men and 110 women, mean age
      59 +/- 10 years. The mean follow-up was 50 +/- 28 months. After transplantation,
      there was a high prevalence of hypertension (67%), hypercholesterolemia (46%),
      diabetes mellitus (42%), and chronic kidney disease (45%). Out of 333 patients in
      the study, 96 patients (29%) died during follow-up. Stepwise logistic regression
      was performed to identify the risk factors that might influence long-term
      mortality outcomes. Based on pretransplant characteristics, positive independent
      risk factors that increased mortality were age at transplant and hepatitis C.
      After transplantation, positive predictive factors were diabetes mellitus and
      cancer. A negative predictive risk factor for mortality was hypercholesterolemia.
      Analysis of medication after transplantation showed that positive predictive
      factors were the use of insulin, steroids, and antibiotics. Negative predictors
      for mortality were tacrolimus and mycophenolate. Our data suggest that diabetes
      mellitus and hepatitis C play an important role in worsening posttransplant
      mortality. 

PMID- 24897626
TI  - Choosing an appropriate sample interval for instantaneous sampling.
AB  - When using instantaneous sampling for collecting data, the interval between two
      succeeding scans is crucial. Utilising either too short or too long time
      intervals may produce erroneous results. A three-step procedure for graphically
      determining optimal sample interval for a behaviour pattern of an individual is
      presented. Two examples, data of a computer simulation and a living antelope
      illustrate the procedure. Finally, some general recommendations for an
      application of the procedure are given. 

PMID- 24897627
TI  - Are faces special for sheep? Evidence from facial and object discrimination
      learning tests showing effects of inversion and social familiarity.
AB  - We have previously shown that sheep, like monkeys, have neural circuits within
      the temporal lobe that respond preferentially to faces. They can also
      discriminate between sheep, humans and other animals on the basis of facial cues
      using an enclosed Y-maze. In the present study we investigated the speed with
      which Clun Forest sheep learn to discriminate between familiar and unfamiliar
      faces, as opposed to symbols, in order to gain a food reward using the same Y
      maze apparatus. Animals (n = 10) received 1 day of training where projected
      images of the pairs of faces or symbols were paired for 20 trials with a picture
      of either an empty or full bucket of food (which indicated which choice of face
      or symbol would result in the animal receiving a food reward) and on the next 4
      days they were given a further 20 trials a day with the faces or symbols alone.
      Results showed that sheep learned significantly faster (by day 1 or 2 post
      training) to recognise sheep faces of a familiar breed compared to geometrical
      symbols (3-4 days post training). Learning using faces of animals of another
      unfamiliar breed was also significantly better than for symbols but was
      significantly worse than that seen using faces of a familiar breed. Inverting the
      faces significantly reduced learning speed for faces of a familiar breed but not
      for that of an unfamiliar one. Inverting familiar objects, food buckets, also did
      not impair discriminatory performance. In a further set of trials where
      discrimination learning was made more difficult by excluding cued trials and
      reducing the number of daily trials to eight, social familiarity was found to
      further improve the animal's ability to learn to discriminate between the faces
      of a familiar breed. Finally, while discriminatory performance for adult sheep
      faces was very good, that for young lamb faces was poor, with only one animal
      learning to choose the face associated with food. It was confirmed in maternal
      ewes that they were also slow to learn to recognise the faces of their lambs (2-3
      weeks). Overall these results show that sheep can learn to distinguish between
      individual adult sheep faces but that breed and social familiarity influence the
      level of performance. Further, discrimination learning of familiar and unfamiliar
      facial stimuli is better than between simple geometrical symbols, indicating that
      faces may be preferentially processed by the brain compared to other objects
      suggesting that faces are indeed special in this species as has been claimed for
      human and non-human primates. 

PMID- 24897628
TI  - Influence of a conspecific image of own vs. different breed on fear reactions of
      ewes.
AB  - We observed the influence of slide images of conspecifics on fear reactions of 12
      Romanov and 12 Ile-de-France ewes. Each ewe was individually tested twice in
      isolation: once in the presence of the projected image of an unfamiliar ewe of
      its own breed, and once when exposed to an image of a ewe of a different breed.
      Ewes' responses to a slide of an individual of their own breed differed
      consistently from their responses to a slide of the other breed (i.e., they
      displayed lower fear reactions to their own breed). There was also a significant
      main effect for breed of subject, which reflects breed differences in activity
      level and/or fearfulness. Differential responses to two-dimensional images of
      unfamiliar animals of own versus other breed suggest that the ewes recognized the
      characteristics of their breed. Moreover, the manner in which ewes responded to
      the slide projections indicates that those images were perceived as social
      stimuli. 

PMID- 24897629
TI  - Depressive illness and behavioral modifications in children. The study of head
      and trunk mobility.
AB  - The study of behavioral activity in depressed adults has given rise to many
      publications. On the other hand, there is currently no published research on
      behavioral modifications in child depression. This work uses the 'Berner system'
      to quantify the head and trunk mobility of children aged 7-13 years, hospitalized
      for a major depressive episode, during a standardized interview recorded on
      video. An analysis compares the results obtained on DA (day admission, before
      treatment) and DD (day discharge, after clinical improvement), and for a control
      sample. Contrary to rotational and lateral movements, the frequencies of sagittal
      movements varied between the two phases of the illness for both the head and
      trunk. However, the position of the head turned downwards was not characteristic
      of the depressed state. 

PMID- 24897630
TI  - Familiarity interferes with filial imprinting.
AB  - The present study was performed to investigate whether and how pre-exposure to an
      object affects subsequent filial imprinting to that object. In Experiment 1
      junglefowl chicks (Gallus gallus spadiceus) were first exposed to either a red
      object alone (control group), or a red and a yellow object simultaneously
      (experimental group; phase 1). Subsequently, all chicks were exposed to the
      yellow object in the presence of a black and blue one (phase 2). At the end of
      phase 1, most experimental chicks had developed a preference for the red object
      over the yellow one. At the end of phase 2, preferences of experimental chicks
      were shifted away from the yellow object towards the novel black and blue object,
      relative to preferences of control chicks. This shows that pre-exposure may
      interfere with imprinting. Experiment 2 revealed that when control chicks were
      tested with the yellow object at the end of phase 1, filial responses were as
      strong as in experimental chicks. This shows that the yellow object had not
      acquired control over filial behaviour during phase 1, and also that the
      relatively impaired imprinting on that object in phase 2 was not due to reduced
      generalization from the red object. One possible explanation why pre-exposure may
      interfere with imprinting is that familiarity alters the level of attention
      attracted by an object, a mechanism suggested to underlie 'latent inhibition' in
      conditioning. 

PMID- 24897631
TI  - Some characteristics of spatial associative memory in the pigeon, Columba livia.
AB  - Willson and Wilkie (1993) developed a novel procedure to assess pigeons' memory
      for the spatial location of food. Only one of four locations provided food each
      daily session. Each location consisted of an illuminated pecking key and grain
      feeder. Over different days different locations, randomly selected, provided food
      during a 16-min session. The pigeons tended to revisit the location at which food
      was found on the previous day thereby demonstrating memory for food-spatial
      location associations over 24 h. Three experiments were conducted to further
      investigate this phenomenon. In Experiment 1 the session duration was varied
      between 4 and 32 min. Longer sessions had no detectable effect on their ability
      to remember the rewarded location 24 h later, a result that suggests that only
      brief encounters with food at a particular location are necessary for recall. In
      Experiment 2 the necessity of an active search for the day's rewarded location
      was removed; a 5-min period in which only the rewarded key was lit preceded the
      regular 16-min session. Pecks to the lit key in this 5-min period produced grain
      on the standard schedule. This manipulation facilitated the pigeons' discovery of
      food but did not affect their ability to remember the rewarded location,
      suggesting that the process of search and discovery is not essential to the
      associative memory process. In Experiment 3, food was available during the
      complete session (non-depleting condition) or was available only during the first
      half of the session (depleting condition). No detectable differences in the
      birds' memory of yesterday's profitable location were found. This suggests that
      non-depletion of food is not a necessary condition for day-to-day recall of food
      location. Taken together these findings enlarge our understanding of the spatial
      associative memory process. 

PMID- 24897632
TI  - Field observations of time-place behaviour in scavenging birds.
AB  - Encoding the spatial location and the time at which significant biological events
      occur is thought to be a fundamental way in which one form of memory is organized
      in animals (Gallistel, 1990, The Organization of Learning. MIT Press, Cambridge,
      MA). If this is true, one would expect to find evidence of this process in a wide
      variety of animals and in a wide number of situations. We report field
      observations of scavenging birds at two outdoor locations at which people tend to
      congregate and eat food, primarily around midday. Scavenging birds appeared to
      anticipate this peak in food availability and arrived at these locations before
      the number of people was at a maximum; time of day, not the absolute number of
      people, was the best predictor of the number of birds at both sites. At a third
      location where food is not consumed this relationship was not observed. Taken
      together these observations support the notion that animals represent the spatial
      and temporal characteristics of biologically important events and use this
      knowledge to forage efficiently. 

PMID- 24897633
TI  - Within-session patterns of responding when rats run in a T-maze.
AB  - Free-operant responding changes systematically within experimental sessions,
      usually increasing and then decreasing, even when the contingencies of
      reinforcement remain constant within the session. The present study extended this
      finding to running times in a T-maze. In Experiment 1, running times changed
      significantly within the session. Furthermore, the within-session pattern of
      running times changed with changes in the amount or rate of reinforcement. In
      Experiment 2, the within-session change in running times was found to be
      independent of the accuracy of responding. In Experiment 3, manipulating whether
      responding and/or reinforcement occurred early in the session did not affect the
      pattern of running times later in the session. The present results increase the
      generality of within-session changes in responding to a discrete-trials
      procedure. Furthermore, within-session patterns of running times usually changed
      in a similar manner as within-session patterns of free-operant responding when
      similar factors were manipulated. Thus, the same factors may be producing the
      changes in both situations. 

PMID- 24897635
TI  - Delayed matching in pigeons: can apparent memory loss be attributed to the delay
      of reinforcement of sample-orienting behavior?
AB  - In earlier research using constant-delay matching with pigeons, there is evidence
      that delay of reinforcement of sample-orienting behavior may contribute to the
      decline in matching accuracy with increasing delay between sample and comparison
      stimuli. In the present research using this procedure, we found that a
      significant decline in matching accuracy between the first and second session can
      occur when delays are relatively long. This effect cannot be accounted for in
      terms of either additional memory loss or surprise (generalization decrement)
      associated with the increase in delay. Furthermore, the decline in matching
      accuracy occurred regardless of whether the delay was inserted between samples
      and comparisons (where it would be expected to affect the use of sample memory in
      making the comparison choice response) or between comparisons and reinforcement
      (where it would not be expected to affect the use of sample memory in making the
      comparison choice response). Thus, the decrease in matching accuracy between
      Session 1 and 2 following an increase in delay appears to be unrelated to sample
      memory at the time of choice. Instead, the results suggest that delay of
      reinforcement of sample-orienting behavior may play an important role in the
      negative slope of the retention functions obtained when constant- or mixed-delay
      matching procedures are used to assess animal memory. 

PMID- 24897636
TI  - The influence of current-visit experience within a prey patch on patch
      persistence.
AB  - A critical component of efficient foraging behavior is leaving a feeding site
      when prey density in that site declines. If ''real time'' hypotheses are to
      explain patch-leaving mechanisms, we will need to examine the influence that
      moment-to-moment experience within a current prey patch has on persistence in
      that patch. We used linear regression to investigate how current experience of
      patch quality influenced homing pigeons' patch persistence. We did this by
      examining the amount of variance in persistence that was accounted for by
      different measures of within-session patch quality. The importance of several
      measures of the precise sequence of events in individual sessions were assessed
      with selected averaging algorithms. Mean inter-capture interval and mean number
      of inter-capture pecks accounted for a significant amount of the variance in
      giving-up time in three of four, and four of four birds, respectively.
      Conversely, only one rate measure in one bird showed an influence on patch
      persistence. In three birds, recent information had a strong influence on giving
      up time. Current-visit experience did influence the patch persistence of the
      pigeons, but the birds' behavior indicated that different individuals used
      different measures of patch quality, different mechanisms of assessing those
      measures, and different patch-exit mechanisms. 

PMID- 24897637
TI  - Wether ewe know me or not: the discrimination of individual humans by sheep.
AB  - A growing literature suggests that animals of various species can discriminate
      between individual humans. In the present study, 15 experimentally naive sheep
      were rewarded for making a nosepress response in the presence of one handler (S+)
      and non-reinforced for this behavior in the presence of a second person (S-). All
      animals responded significantly more to the S+ handler (P<0.001) during non
      reinforced test trials. Furthermore, sheep engaged in clearly different behavior
      during a 10-s pre-trial period, depending on which handler was present. Control
      conditions preclude discrimination based on order effects, temporal cues, or a
      win-stay/lose-shift learning set. The ability to differentiate between individual
      humans, regardless of its sensory basis, suggests that animals can use humans to
      predict the delivery of hedonic events that routinely occur in research settings.
      The resultant human-based operant and Pavlovian conditioning has implications for
      the design of research protocols and the interpretation of results. 

PMID- 24897638
TI  - Development of feeding selectivity in roe deer.
AB  - The development of feeding behaviour in European roe deer (Capreolus capreolus)
      was studied using nine fawns, from birth to 1.5 months. They were offered
      individually, seven plant species in random order, one at a time, and their
      feeding behaviour recorded. The results were compared to the behaviour of eight
      adults offered the same plants, which were chosen to cover the whole range from
      preferred to strongly avoided plants. Fawns displayed selectivity towards the
      different plants from their first contact, and they appeared to respond initially
      to buccal, but not olfactory, stimuli. Thereafter consumption of the two
      preferred species increased, while use of the others remained at a very low
      level. For the two plant types most strongly avoided (and perhaps the most
      toxic), learning allowed the deer to distinguish and avoid the plants using
      olfactory (and perhaps also visual) stimuli. For the other three species, fawns
      continued to ingest small quantities which may have allowed them to learn to
      avoid these plants, using the association between taste and negative post
      ingestive consequences. This process may also have been involved in the increases
      in the consumption of the two preferred species. The animals were able to
      discriminate to almost the same extent as adults by the time they were about 1
      month old. These results underline the importance of learning, and identify some
      of the stimuli involved in the development and maintenance of the highly
      selective and flexible feeding behaviour of this herbivore. 

PMID- 24897639
TI  - An investigation into the occurrence of spontaneous alternation behaviour in the
      domestic hen.
AB  - Spontaneous alternation behaviour (SAB) refers to the tendency for animals to
      alternate their choice of arms in successive runs of a T- or Y-maze. Despite the
      apparent reliability of the phenomemon in the laboratory rat, there has been
      little examination of SAB in other species. Previous studies in domestic fowl
      have shown no evidence of SAB, although it was inferred that regular handling
      might reduce alternation behaviour. The present experiment used two groups of six
      adult hens, with one group receiving a handling treatment prior to the maze
      trials. The hens were given six runs per day for 9 days in a T-maze in which one
      arm was red and the other green, with colour balanced for treatment. It was shown
      that the number of 'looks' made down the arms of the maze was positively
      correlated with alternation rate, indicating that decision-making processes may
      be involved in alternation behaviour. Generally, low levels of alternation were
      shown, but two hens performed above chance levels of alternation and three hens
      performed below this level. There was no effect of handling treatment on
      alternation rate. It is suggested that species differences in the level of
      alternation performed may reflect the primary exploratory modality of the animal
      concerned. 

PMID- 24897640
TI  - Effect of group size on tonic immobility in laying hens.
AB  - It has been shown that duration of tonic immobility (TI) reflects predation risk
      and levels of fearfulness. Since the chances of escaping predation are higher in
      larger groups, birds from these groups should have shorter TI duration. On the
      other hand, increased competition between birds in larger groups might lead to
      greater fearfulness and longer TI in larger groups. The aim of this study was to
      test these two hypotheses. Laying hens raised in floor pens in group sizes of 15,
      30, 60 and 120, each with four replicates, were used. Tonic immobility tests were
      performed on adult birds, either directly 'in' their home pen or 'out' in a
      separate room. In the test 'in', duration of TI increased with group size, with a
      significant difference between group sizes 15 and 120 (P=0.012). In the test
      performed 'out', there was a trend for TI to be longer in larger groups. The
      duration of TI in groups tested 'in', was significantly shorter than in groups
      tested 'out' (P<0.00l). The results of this study suggest that although the
      ultimate function of TI is to reduce predation, the social environment is a
      proximate factor affecting TI duration in domestic hens. 

PMID- 24897641
TI  - Physical condition at weaning affects exploratory behaviour and stereotypy
      development in laboratory mice.
AB  - Laboratory mice of the ICR strain develop two morphologically distinct forms of
      stereotypy in the post-weaning period when kept under standard housing
      conditions. Wire-gnawing develops from single bites at the cage-lid during
      exploratory climbing whereas jumping originates from exploratory rearing at the
      cage wall. In a recent study nude mutants of ICR that were physically retarded
      around the age of stereotypy development performed more rearing but less climbing
      just after weaning and subsequently developed more jumping but less wire-gnawing
      than ICR mice (Wurbel, H., Stauffacher, M. and von Holst, D. 1996. Ethology 102:
      371-385). The two source behaviour patterns, climbing and rearing, could
      represent alternative strategies serving the same goal (e.g. exploration of
      external stimuli, escape). Since the ability to climb may depend on physical
      strength, preference for either of these two patterns may be determined by
      physical condition to some extent. As a consequence, the prefered pattern may
      determine the later form of stereotypy. To test these two hypotheses, 48 male ICR
      mice were assigned to three groups of 16 each. One group was prematurely weaned
      at day 17 to mimic physical retardation, the others were weaned at the standard
      weaning age of 20 days and divided into two groups of high and low weaning
      weight. Premature weaning was associated with a shift in the relative proportions
      of climbing and rearing towards rearing. Although heavy males showed most
      climbing and least rearing, weaning weight did not significantly affect
      performance of these two patterns. Subsequently, all mice developed stereotypic
      wire-gnawing but none of them showed stereotypic jumping. Although weaning age
      affected the performance of the two source behaviour patterns in the predicted
      way, the differences may not have been large enough to cause different forms of
      stereotypy. However, both, premature weaning and low weaning weight resulted in
      higher stereotypy performance when adult. 

PMID- 24897642
TI  - Side-to-side head movements to obtain motion depth cues: A short review of
      research on the praying mantis.
AB  - In the case of a visual field comprised of stationary objects, retinal image
      motion and motion parallax initiated by the observer can be used to determine the
      absolute and relative distance of objects. The principle is simple: when the
      observer moves, the retinal images of objects close to the eye are displaced more
      quickly-and through a larger angle-than are the retinal images of more distant
      objects. It is remarkable that not only in humans, but throughout the animal
      kingdom, from primates down to insects, retinal image motion and motion parallax
      generated with the aid of head movements is used as a means of distance
      estimation. In the case of praying mantids, translatory side-to-side movements of
      the head in a horizontal plane are performed to determine the jump distance to
      stationary objects. The relevant parameter for determining the distance to the
      object is the speed of retinal image motion. The motion of the head must,
      however, also be monitored. This requires a multisensory regulatory circuit.
      Motion parallax information seems to be mediated by a movement-detecting neuronal
      mechanism which is sensitive to the speed of horizontal image motion,
      irrespective of its spatial structure or direction. 

PMID- 24897643
TI  - Female prairie voles (Microtus ochrogaster) fail to form a new pair after loss of
      mate.
AB  - We tested experimentally the hypothesis that failure to acquire a new mate by
      monogamously paired female Microtus ochrogaster that lose their mate represents
      pair-bonding behavior, not a lack of available males. Males were removed from
      reproductive male-female pairs and the females provided an opportunity to pair
      with unfamiliar sexually inexperienced or experienced males in a semi-natural
      arena. Only three of 22 (13.6%) females formed a new pair, two with inexperienced
      males and one with an experienced male. Three other females spent more time with
      an experienced male than with the inexperienced male, but did not form a pair or
      co-nest with that male. The results confirm field observations that availability
      of males is not a factor in the failure of female prairie voles to form a new
      pair following loss of their mate. This study concludes failure to form a new
      pair is associated with pair-bonding behavior. 

PMID- 24897644
TI  - Face recognition in primates: a cross-species study.
AB  - Recognition for human faces, monkey faces, and objects was assessed in both adult
      humans (Homo sapiens) and monkeys (Macaca mulatta) with a visual paired
      comparison task. The results demonstrated that while both species showed strong
      novelty preference for objects, human participants showed novelty preference for
      human faces but not for monkey faces, and vice versa for the monkeys. This
      'species-specific effect' in face recognition is discussed in relation with data
      on both the 'other-race effect' observed in humans and the effects of experience
      or training on face recognition processes in primates. 

PMID- 24897646
TI  - Editorial.

PMID- 24897645
TI  - Acquisition, extinction, and reacquisition of responding with delayed and
      immediate reinforcement.
AB  - The present study investigated acquisition, extinction, and reacquisition of free
      operant responding when rats' lever presses produced water after a resetting
      delay of 0, 10, 20, or 30 s. Results indicated that: (1) responding was acquired
      rapidly at all delays without shaping or autoshaping; (2) resistance to
      extinction was directly related to delay length and inversely related to
      intermittency of reinforcement; (3) responding acquired with delayed
      reinforcement recovered less rapidly from extinction, and was less efficient,
      than responding acquired with immediate reinforcement. Comparing these results
      with those of studies using discrete-trials and free-operant procedures with no
      reinforcement delay suggest that the specific conditions under which behavior is
      maintained determines, in part, the behavioral effects of delay and intermittency
      of reinforcement. 

PMID- 24897647
TI  - Distinctive trends in fundamental and applied ethology: Some general indications
      from the contents of two Elsevier journals in animal behaviour.

PMID- 24897648
TI  - An informational analysis of antennal communication during trophallaxis in the
      ant Myrmica Rubra L.
AB  - Trophallaxis by ants is accompanied by antennal movements which have an
      informational value. The succession of contacts permits the transmission of
      information for triggering, maintaining or stopping the exchange. The use of
      information theory indicates that antennal contacts during trophallaxis
      quantitatively transmit much less information than some other systems used by
      social insects (i.e. the dance of the bees or trails of Solenopsis). The
      information transferred by the signal is never more than 20%; the system is not
      appropriate to conduct important messages but belongs to a modulatory
      communication system. 

PMID- 24897649
TI  - Vocal response of male European water frogs (Rana Esculenta complex) to mating
      and territorial calls.
AB  - The responses of male European water frogs (the two species Rana lessonae and
      Rana ridibunda and their hybrid, Rana esculenta) to playback of their mating and
      territorial calls were studied during the mating season. In order to select
      biologically relevant intensities for the presentation of the recorded calls, the
      sound pressure of the calls produced by the frogs themselves was established
      prior to the experiment. At a distance of 1 m the most intense calls were those
      of R. ridibunda, with a sound pressure of 110 dB (peak SPL). The smaller males of
      R. esculenta gave calls about 5 dB lower in intensity. The calls of R. lessonae,
      the smallest phenotype, were still less intense, 10 dB lower than those of R.
      ridibunda. The territorial calls of all three phenotypes elicited territorial
      calls in all of the males tested, as a rule accompanied by approach to the sound
      source. The sound pressure required to elicit a vocal response was nearly the
      same for each of the three different territorial calls. Sometimes encounter calls
      and warning calls were given in addition to territorial calls. When the mating
      calls were presented at low intensity, in some cases the males responded with
      their own mating calls. Mating calls at higher intensity elicited the same
      behavior that appeared following presentation of territorial calls, but
      significantly higher sound pressures were required to elicit such a response to
      mating calls than to territorial calls. The males of R. lessonae and R. esculenta
      did not respond to the mating calls of R. ridibunda, and each of them had
      significantly lower thresholds to the mating call of its own phenotype than to
      that of the other. The males of R. ridibunda responded only to conspecific mating
      calls. The vocal-response thresholds are compared with those of the electrodermal
      response reacting to the same stimuli. The significance of the different calls of
      the European water frogs is discussed. 

PMID- 24897650
TI  - Attack and defense in laboratory and wild Norway and black rats.
AB  - Intra- and interspecific agonistic encounters in Long-Evans and field-trapped
      Rattus norvegicus and Rattus rattus showed a consistency in the form and
      character of attack and defensive behaviors. Colony alpha males exhibited high
      levels of lateral attack, on-top, and chasing behaviors which resulted in a high
      percentage of bites on the intruder's back. Bites directed to the back were
      countered by intruders through the utilization of boxing, on-back, and flight
      defense. These findings indicate that agonistic interactions in Rattus are
      underlined by back-attack and back-defense strategies. A sex difference in biting
      was also consistent across strains: males bit the back and flanks and females the
      head of an anesthetized stranger which suggest differences in the motivation of
      male and female attack. 

PMID- 24897651
TI  - Capacity of working memory in rats as determined by performance on a radial maze.
AB  - Capacity of the working memory was tested in 12 rats highly overtrained in the 12
      and 24-arm radial mazes. Asymptotic performance levels were characterized by
      1.01 and 2.78 errors/trial in the 12- and 24-arm mazes, respectively. The
      incidence of errors increased from 31% on the last choice in the 12-arm maze to
      51% on choices 23 and 24 in the 24-arm maze, but remained significantly below the
      expected error probability of about 85%. Linear extrapolation of the above trend
      to mazes with more arms suggests working memory capacity of 40 to 50 items. When
      two trials in a 12-arm maze were repeated in immediate succession, error
      incidence increased from 1.17 in the first trial to 2.13 in the second trial. The
      tendency to avoid choice repetition could be observed in any string of 12
      continuous choices, but was weakest in segments divided by trial boundary (2.48
      errors in choices 7 to 18). With a different trial separation (choices 1-6 and 19
      24 in maze A, choices 7-18 in an adjacent maze B) errors dropped to 1.09 in B but
      increased to 2.30 in A. It is concluded that radial maze performance reflects
      avoidance of choice repetition which is improved by recognition of trial
      boundaries and is adversely influenced by forgetting and interference. 

PMID- 24897652
TI  - Seasonal changes in retinal function of the frog Rana Ridibunda.
AB  - The electroretinogram (ERG) of Rana ridibunda was recorded at different times of
      the year. The frogs exhibited distinct seasonal changes in various parameters of
      the ERG. The amplitudes of both the a- and the b-waves were greater in summer
      than in winter. With a luminance of 3000 cd/m(2) the mean amplitude of the a-wave
      ranged from minimal 30 MU V (February) to maximal 60 MU V (July), and that of the
      b-wave from 190 MU V (February) to maximal 550 MU V (June). Average latency was
      about 28 ms in winter and 14 ms in summer. The greatest difference was found in
      flicker-fusion frequency which averaged 29 Hz in July and 9 Hz in January. There
      was also a significant change in the average threshold for response to white
      light (0.011 cd/m(2) in March). 

PMID- 24897653
TI  - Object permanence in cats: Analysis in locomotor space.
AB  - Stages IV and V object permanence were studied with 38-40-week-old cats. A
      constraining apparatus preventing animals from pursuing the bowl containing meat
      before it was concealed was used. Either the bowl was seen moving and disappeared
      from view behind a screen (stage IV trials), or after this sequence, it
      reappeared from behind the first screen and disappeared behind a second screen
      (stage V trials). In both situations cats performed significantly above chance
      but the paths taken to reach the food were different according to the stage. In
      stage V trials, cats expressed a preference for the path leading to the end of
      the second screen where the food was last seen disappearing. 

PMID- 24897654
TI  - Effects of previous familiarization on novelty reactions in mice (Mus musculus).
AB  - Mice were at first familiarized with a large novel cage during either 0, 15 min,
      1 h, 12 h, 24 h or 48 h. On the following day, they were observed for a 5-min
      period after having freely entered the previously explored cage. Forty five
      behavioural items were recorded as well as entrance latency, total time spent in
      the large cage and transitions between the cage and the nest. Results allowed us
      to distinguish three groups: the most familiarized mice (24 and 48 h), the less
      familiarized ones (naive and 15 min) and the intermediate group (1 and 12 h). It
      appears that, for the most familiarized mice, there was a topographic continuity
      between the familiar and the novel environment. 

PMID- 24897655
TI  - The meaning of the 'variations' in the babbler 'shout': A musical-ethological
      approach.
AB  - This study is focused on the shout of the babbler Turdoides squamiceps, as a
      model for interpreting the meaning of the variations in animal vocal expressions,
      using a 'musical-ethological approach'. Vocalizations were recorded in nature,
      where all babblers were individually marked. The field events were classified
      into different communicative categories, and the recordings of 170 shouts of the
      eight most intensively studied babblers, were analyzed with respect to the 'basic
      rules' observed in music. Visually defined 'variation types' and mathematically
      defined musical variables of the variations were related to the birds' field
      behaviour in order to determine the correlations between the variations and the
      different categories. The results indicate the existence of variations in the
      babbler shout that may be important for communication. Border situations were
      accompanied by longer 'syllable variations' and by an increase in the musical
      variables, which were defined according to the 'basic rules' observed in music.
      Other, more subtle variations of the intensity curves could be related to
      motivations such as joining the group members or searching for affiliation. An
      increase in the distance between communicating babblers was accompanied by an
      increase in the number of syllables per shout. It is suggested that this is
      because the variations in the tempo and staccato are better identified in long
      shouts with many syllables. It is suggested that variations in vocal expressions
      play a role in animal communication. The resemblance of the 'basic musical
      factors' of the variations in the babbler shout to the basic rules observed in
      human speech intonation and in music suggests that the same set of rules may be
      found in many other animals. Thus, it is appropriate to apply certain musical
      terms to animal communication. 

PMID- 24897656
TI  - Performance of domestic hens under progressive-ratio schedules of food delivery.
AB  - Domestic hens were exposed to progressive-ratio 2 and progressive-ratio 10
      schedules of food delivery with different initial ratios (2, 10, 20, 30, and 40).
      Breaking points, defined as the largest ratios completed before responding ceased
      for 600 consecutive seconds, were recorded under all conditions. In general,
      breaking points were higher under the PR 10 schedule than under the PR 2
      schedule, and the value of the initial ratio did not systematically affect the
      breaking point. The former finding suggests that relative satiation affected
      breaking points in the present study, but the latter finding suggests that the
      primary determinant was the 'price' of the reinforcer, defined in terms of the
      number of responses required to produce it. Breaking points were similar under
      conditions where initial ratios changed from session to session and under more
      conventional conditions, where initial ratios remained unchanged over several
      sessions. 

PMID- 24897657
TI  - Regurgitation behaviour of the Lasius flavus worker (Formicidae) towards the
      myrmecophilous beetle Claviger testaceus (Pselaphidae) and other recipients.
AB  - The regurgitation behaviour of the Lasius flavus worker towards the
      myrmecophilous beetle Claviger testaceus and other recipients is compared.
      Examination of the antennal and mandibular positions and of the dynamics of the
      functioning of the cephalic alimentary pump shows that the workers regurgitate
      their crop contents on the Claviger in the same manner as they do on insect
      cadavers, which are in a state to be given as solid food to the larvae. The
      workers regurgitate differently to ant larvae and, especially, to other workers,
      gynes and males. Concerning regurgitation, the workers thus handle the guest
      beetle as an insect cadaver. As they regurgitate in response to particular
      secretions of the Claviger, it may be inferred that the regurgitating allomone
      emitted by the beetle mimics the action of a substance produced by decaying
      insect corpses. The observation of the functioning of the cephalic alimentary
      pump shows that, in L. flavus, 'regurgitation' of ingluvial liquid on the
      Claviger or a cadaver comprises a few disgorging movements followed by numerous
      reingesting movements. When the receiver is an ant imago, regurgitation is more
      complex and characterized by rapid alternations of food fluxes and refluxes in
      the donor worker, during which process the ant constantly maintains a typically
      external donor posture. The function of the workers' regurgitation upon insect
      cadavers is discussed. It is hypothesized that this behaviour is instrumental in
      ensuring the extraoral enzymatic digestion of solid meaty food given to larvae or
      in providing them with a more balanced diet. Cannibalism in L. flavus is also
      discussed. 

PMID- 24897658
TI  - Signal intensity and duration estimation in rats.
AB  - Rats were trained on a short (2-second) versus long (10-second) duration
      discrimination. The duration of an overhead light signaled which of two lever
      press responses, left or right, would produce food reinforcement. After the rats
      had acquired the discrimination, probe tests were presented in which the light
      varied in intensity (bright or dim) and duration (values between 2 and 10
      seconds). The results indicated that rats judged a bright light to be longer than
      a dim light of equal duration. Signal intensity has been shown to affect timing
      in humans and pigeons. The present results therefore extend the comparative
      generality of the effect to include rats as well. 

PMID- 24897659
TI  - Developmental analysis of habituation of the acoustic startle response in the
      preweanling and adult rats.
AB  - Our experiments assessed the build-up of short-term and long-term habituation of
      the acoustic startle response in preweanling and adult rats. Results showed that
      the adult rats demonstrated both short-term and long-term habituation of the
      acoustic startle response (ASR). In contrast, the decreased responsiveness to the
      auditory stimulations was revealed in the preweanling rats only 2 hours after the
      training session, whilst 24 hours and 48 hours after learning no significant
      change of the startle amplitude in the rat pups was detected. The data are
      discussed with respect to maturational interpretations of age-related differences
      in learning and retrieval processes. 

PMID- 24897660
TI  - Are socially acquired behaviours irreversible?
AB  - Norway rat subjects were exposed for either 3 or 10 days to conspecific
      demonstrators eating a cinnamon-flavoured, protein-deficient diet. While in
      contact with their demonstrators, and for several days thereafter, subjects were
      offered a choice between the cinnamon-flavoured, protein-deficient diet that
      their demonstrators were eating and a less palatable, nutmeg-flavoured, protein
      rich diet. While subjects were in contact with their respective demonstrators
      they ate little protein-rich diet; during the 7 days immediately following
      removal of demonstrators from the experiment, subjects learned to eat sufficient
      amounts of protein-rich diet to permit normal growth. The results indicate that
      effects of social influence on food choice are transitory. They suggest that the
      time scale on which animals learn individually to modify socially acquired
      behaviour is considerably shorter than usually considered in discussions of
      quantitative models of the evolution of social learning processes. 

PMID- 24897661
TI  - Within-session changes in responding when rate and duration of reinforcement
      vary.
AB  - Three pigeons responded on variable interval 60-second and variable interval 30
      second schedules. The duration of access to mixed grain was varied from 2-to 20
      seconds per reinforcer in different conditions. Within-session patterns of
      responding did not differ when subjects received 2- versus 20-seconds access to
      the reinforcer for the schedule providing the lower rate of reinforcement.
      However, the within-session decreases in responding were steeper when reinforcers
      were 20-seconds than when they were 2-seconds for the schedule providing the
      higher rate of reinforcement. These results indicate that satiation is not
      necessary to produce within-session changes in responding, but it may contribute
      to those changes at high rates of reinforcement. 

PMID- 24897662
TI  - The effect of prior victory or defeat in the same site as that of subsequent
      encounter on the determination of dyadic dominance in the domestic hen.
AB  - We examined the effect of prior victory or defeat in the same site as that of a
      subsequent encounter on the outcome of dyadic encounter of domestic hens by
      placing them in two situations. In the first set of dyads, two unacquainted hens
      having experienced prior victory were introduced in the site where one had
      experienced victory. In the second set, two unacquainted hens having experienced
      defeat were introduced in the site where one had recently lost. Results indicate
      that victories are equally shared between individuals with prior victory
      experiences, while familiarity with the meeting site did not give any advantage.
      However, hens having previously lost were disadvantaged when the encounter
      occurred in the same site as that of their prior defeat. This demonstrates that
      previous social experience in a site is more important on the outcome of
      subsequent encounters for losers than winners. Losers seem to associate the site
      with the stressful effect of losing or being more easily dominated. 

PMID- 24897663
TI  - Predator-prey interactions, reosurce depression and patch revisitation.
AB  - Generalist predators may be confronted by different types of prey in different
      patches: sedentary and conspicuous, cryptic (with or without refugia),
      conspicuous and nonsocial, or conspicuous and social. I argue that, where
      encounter rates with prey are of most importance, patch revisitation should be a
      profitable tactic where prey have short "recovery" times (conspicuous, nonsocial
      prey), or where anti-predator response (e.g. shoaling) may increase
      conspicuousness. Predictions are made for how temporal changes in prey encounter
      rates should affect revisit schedules and feeding rates for the 4 different prey
      types. 

PMID- 24897664
TI  - Behavioural correlates of extrinsically reinforced video game play.
AB  - Three experiments which investigate human observers' conceptions of the nature of
      extrinsic reinforcement correlated behaviour (ERCB) are reported. in the first
      two experiments, observers viewed players at a video game under conditions of
      extrinsic and no extrinsic reinforcement. Observers' tasks were to identify the
      extrinsic reinforcement periods and to provide evidence for these by referring to
      any player behaviour. The observer statements were submitted to content analyses
      from which emerged a number of ERCB categories, the most frequently reported ones
      being 'control grip', 'time taken between games', 'movements' and
      'smiling/grinning'. In the third experiment the 'smiling/grinning' cue was
      manipulated by instruction to an actor in order to simulate extrinsic and no
      extrinsic reinforcement conditions. Observers were able reliably to identify
      simulated extrinsic reinforcement conditions particularly whenthey reported (and
      presumably had attended to) the changes in the 'smiling/grinning' cue. Various
      implications arising from the suggested existence of ERCB are discussed including
      its place in motivational effects on developmental changes, socialisation
      processes and cross-cultural differences. 

PMID- 24897665
TI  - Social environmental factors influencing mutual recognition of inviduals in the
      ant Leptothorax Lichtensteini bondr. (Hymenoptera: Formicidae).
AB  - In the framework of a study of the mechanisms underlying mutual recognition
      phenomena between members of a Lepthothorax lichtensteini ant colony, we
      conducted two series of experiments, designed to investigate the effects of an
      experimental separation of individuals from their colony upon being reintroduced.
      Two parameters were examined: the length of the separation period and the social
      experience lived by these individuals during their separation. Workers living in
      groups of 5 individuals from the same colony or in an alien colony where they had
      been previously adopted were rejected by their own sisters when they were
      reintroduced into their colony, after a 70- and a 45-day period of separation
      respectively. We moreover investigated the effects on group cohesion of
      separating one colony into two halves, depending on whether of not the queen was
      present. After a 120-day separation, the 2 halves of a colony did not merge
      rapidly and without aggressivity, unless the single reproductive female was
      transferred from the one nest to the other every 15 days during the separation
      period. In the light of the results obtained, we conclude that: 

PMID- 24897666
TI  - Effects of fluprazine hydrochloride on maternal behaviour in mice.
AB  - Fluprazine hydrochloride treatment disrupted both retrieval and nursing
      components of maternal behaviour when dam and pups were separated for a 30 min
      post-infection interval. Subsequent experiments revealed that pup contact during
      this interval, even when restricted to visual/auditory stimulation, abolished the
      drug's effect on nursing but not retrieval. Fluprazine appears to strongly and
      consistently disrupt retrieval while its effects on nursing appear more
      indirectly mediated. The data clearly reveal that the drug's effects extend to
      maternal behaviour as well as aggression, male copulation, play and various fear
      motivated behaviours. This range of behavioural effects may limit its usefulness
      in the reduction of aggression. 

PMID- 24897667
TI  - Social attraction and the feeding behaviour of domestic hens.
AB  - Traditional models of the feeding behaviour of domestic hens (Gallus gallus
      domesticus) predict that dominant birds will attempt to monopolise access tote
      fob-resources and will be intolerant of subordinate birds fending in their.
      proximity. Furthermore, when food is available at a number of different
      (spatially separated sites), birds should disperse when feeding. The results of
      the present study indicated that, at least in small groups of birds, these
      predictions do not hold true. When hens, kept in pens in groups of three, were
      offered the possibility of feeding under various degrees of physical and/or
      visual isolation from one another, (i.e. at a circular feeder quadratically
      partitioned with wood, glass or nominal divisions), they chose to feed in
      proximity to one another (i.e. in the same or adjacent quadrants of the feeder)
      significantly more than expected by chance, irrespective of the degree of
      physical isolation between feeding sites. In a second experiment, one birds of a
      group of three was prevented from feeding with her two pen mates and could only
      feed at a site distal from them. Lader such conditions the "isolated" bird spent
      significantly less time feeding than when it was able to feed with the other two
      birds and presented behaviour (significantly increased levels of locomotor
      activity and preening) possibly symptomatic of frustration. It is suggested that
      feeding birds are strongly attracted to one another and that, at least in the
      strains and group sizes considered, social attraction and available feeding space
      are important influences on the manner in which hens space themselves when
      feeding. 

PMID- 24897668
TI  - Concurrent Schedules: Effects of Blackout during the Changeover Delay.
AB  - Four homing pigeons were exposed to concurrent variable-interval 40-s variable
      interval 120-s schedules of reinforcement with changeover delays of five
      durations (0, 1, 2, 4, and 8 s). The changeover delays of non-zero durations were
      presented with and without blackout of the experimental chamber in different
      conditions. Blackout eliminated or strongly reduced responding during the
      changeover delay. It decreased the run length of responding after the changeover
      delay in the variable-interval 120-s component, but it had no systematic effects
      on the run length after the changeover delay in the variable-interval 40-s
      component. In both components, the run lengths after the changeover delay
      increased with the duration of the delay. Blackout increased deviations from
      response matching, computed from measures of responding after the changeover
      delay. The deviations increased with the duration of the changeover delay. The
      reults suggest that the finding of overmatching with procedures other than the
      changeover delay does not depend exclusively on the absence of responding in the
      interval that elapses between initiation of the change to an alternative and the
      first response eligible for reinforcement. 

PMID- 24897669
TI  - Self and Social Grooming in Stump-Tailed Macaques: Effects of Kin Presence or
      Absence within the Group.
AB  - The relation between individual self and social-grooming scores, asaessingthe
      effects of having or lacking relatives within the group, was studied in a colony
      of stump-tailed macaques (Macacaarctoides). As it has been shown by other
      authors, kinship favoured grooming interactions, so animals lacking relatives wen
      seldom mom as groomees. Conversely, these subjects accounted for the major mounts
      of self-grooming, as if they were surmounting the social grooming deficit. This
      negative relationship between self and social grooming suggests a common
      functional relationship between both forms of behavior, most likely as a reducing
      tension activity. 

PMID- 24897671
TI  - Behavioural validation of a light/dark choice procedure for testing anti-anxiety
      agents.
AB  - In order to teat the behavioural value of a two-chambered light/dark choice
      procedure used for pharmacological studies, we investigated the effects of
      several internal and external factors on two variables: the time spent by mice in
      the lit box (TLB) and the number of transitions between the lit box and the dark
      one. The present results indicate that this procedure can be considered as an
      unconditioned conflict paradigm based at once on the innate tendency of mice to
      seek refuge in a dark box and their propensity to escape novel places into which
      they have been forced. It is suggested that this test is particularly well
      adopted to measuring the antiaversive properties of the so called "anxiolytic"
      drugs. 

PMID- 24897670
TI  - Les Sequences De Remplacement Chez Ctenodactylus gundi: Competition Ou
      Cooperation?
AB  - Ctenodactylus gundi, a colonial rodent inhabiting saharian Atlas, is often seen
      standing at the top of the rocks. At more or less regular intervals, another
      conspecific is taking the place of the "resident" animal. This relief impues only
      amicable reliationships and is to be considered as a kind of cooperation. The
      function of the resident, as a specific element against predation, is discussed. 

PMID- 24897672
TI  - Bisexuality in the prepubertal male pig.
AB  - Intact and castrated male pigs were given weekly tests between the ages of 3 and
      5.5 months with either an adult male or an adult oestrous female partner. All
      intact male subjects mounted, and mounting occurred an early as 3 months of age.
      When mounted by males, 86% of the intact males displayed the female receptive
      posture (immobilization) at least once, and average receptivity scores were high.
      Thus prepubertal male pigs are behaviourally bisexual. Both mounting and
      immobilization were much less frequent in the castrated males; their occurrence
      in intact males is due to testicular hormones. In the intact males, receptivity
      did not decrease during the 30 week testing period, in contrast to evidence from
      previous studies, using adult tests, for progressive defeminization during the
      prepubertal period. 

PMID- 24897673
TI  - Learning and the role of cue reinforcement in the shell cracking behaviour of the
      shore crab: carcinus maenas (L).
AB  - The shell-cracking behaviour of Carcinus maenas as it fed on Littorina littorea
      has been described. Of the various behavioural tactics employed, sawing,
      drilling/prizing, cutting/crushing and poking were found to be most frequently
      used. The establishment of a puncture or crack on the winkle shell while
      harvesting the prey served as an additional cue landing to (1) higher shell
      cracking activity per unit time and (2) more frequent and directional inter
      change or behavioural tactics. Analyses of activity bouts; both on long duration
      basis (> 10s) and acts transition analyses showed that C. maenas shell-cracking
      behaviour is basically repetitive, with the effects of learning showing in the
      efficient utilisation of encounter time rather than in the development of new
      techniques. 

PMID- 24897674
TI  - Influence of experience and visual stimulation in Japanese quail laying site
      selection under experimental condition.
AB  - We raised female Japanese quail until their post juvenile moult in "neutral" or
      simplified environments chosen according to features representative of natural
      habitats. At laying, we placed female quail individually in a choice situation
      with regard to environmental patterns. 9fiey took account of the visual factors
      of. their environment in selecting laying site. We found that female Japanese
      quail preferred a structured achromatic environment over a uniform achromatic
      environment. They showed a preference for vertical grey stripes over horizontal
      stripes and a clear preference for green over ochre. Green vertical and
      horizontal striping proved highly attractive but there was no preference for one
      or another. Juvenile experience does not affect laying site selection but it
      certainly does emphasize preference for green. Individual choice proved to be
      stable but, on the contrary, we found strong interin dividual variability within
      each one of the groups. The results taken as a whole are relevant to the choices
      faced by female quails seeking nest sites in their natural habitat. 

PMID- 24897675
TI  - Age-related changes in aggression in ant cataglyphis cursor (hymenoptera,
      formicidae): influence on intercolonial relationships.
AB  - Cataglyphis cursor forms monogynous societies which may however accept some
      foreign viduals. The factors influencing the degree of aggressiveness of the
      workers have been studied as follows. We have shown that the aggressive behaviour
      is expressed mainly by the foragers, the nurses are very little. aggressive. We
      observe therefore an evolution in the reactivity of the workers to a foreign
      odour in terms of age-related changes. However the closing of the society still
      depends on the behaviour of the foragers. Among the socia insects young workers
      are generally adopted by foreign colonies even if these colonies are completely
      closed to any other adult ants. Experiments allowed us to specify that young
      workers are recognized- as foreigners by another colony after the 4th day of age.
      Afterwards the adopted young ants were put back at different ages into their
      original colony, where they were recognized and accepted ty their sisters. The
      discussion is based on the origin of the colony odour. If this odour is formed
      from cuticular substances, in C. cursor their origin is probably endogenous, and
      predominant in comparison with the odours ac4uired from the environment
      (including that of the adoptive colony). Such an individualistic recognition
      system is known in only one other social insect species, the sweat bee. 

PMID- 24897677
TI  - Probing the sensory property of perylenediimide derivatives in hydrazine gas:
      core-substituted aromatic group effect.
AB  - In this contribution, four perylenediimide derivatives (PTCDIs) with different
      core-substituted aromatic groups were prepared. Studies on their sensing
      properties in hydrazine vapor (10 ppm)  suggested ~5 orders of the magnitude in
      increased current for core-phenyl-substituted DEY was achieved and this value is
      9, 9, and 24 times higher than that of core-pyridyl-substituted DSPY, DFPY, and
      DTPY, respectively. The differential response to the hydrazine vapor is less
      dependent on their surface area and morphologies. The lower LUMO energy and
      activation energy with smaller interplanar spacing allows DEY highly efficient
      sensing performance. A similar face-face packing mode and LUMO energy of DSPY and
      DFPY lead to both of them exhibiting the same sensing performance, while higher
      LUMO energy and head-to-tail packing modes with a greater interplanar spacing
      induce the less-efficient sensing performance of DTPY sensors. Discussions for
      structure-function relationships suggested that aromatic groups in the bay region
      have significant impact on PTCDI sensing performance by modulating energy level,
      interplanar spacing, and stacking modes. 

PMID- 24897678
TI  - Fear responses in domestic chicks as a function of the social environment.
AB  - The open field or novel environment has been used to assess fear in many species
      but its validity for the domestic fowl has recently been questioned. Based
      primarily on experiments which involved manipulation of the social environment
      Gallup and Suarez proposed that, contrary to an emotionality or fear
      interpretation, "open-field behaviour in chickens represents a compromise between
      opposing tendencies to reinstate contact with conspecifics and to minimize
      detection in the face of possible predation". Predictions which can be made from
      the Gallup and Suarez model and from the fear hypothesis were tested by examining
      the effects of manipulating the social environment, during rearing and testing,
      on the open-field, hole-in-the-wall box and tonic immobility responses of
      domestic chicks. The results were inconsistent with predictions made from the
      Gallup and Suarez model but they conformed to the fear hypothesis. Furthermore,
      they were consistent with the majority of findings reported in the literature.
      Thus, while the opposing tendencies of reinstatement and predator evasion are,
      almost undoubtedly, important in many situations there remains considerable
      evidence for the role of fear in regulating the responses of domestic chicks to
      novel environments such as the open field. The two interpretations should not be
      considered mutually incompatible. 

PMID- 24897679
TI  - Behavioural responses to human intruders of herring gulls (Larus Argentatus ) and
      great black-backed gulls (L. Marinus ) with varying exposure to human
      disturbance.
AB  - This study examined differences in response to humans approaching the nest for
      incubating herring and great black-backed gulls with varying amounts of prior
      exposure to humans. Gulls nesting in frequently disturbed areas sat more
      tenaciously, responded more slowly, and returned to the nest more quickly
      following the intruder's retreat, than birds nesting in less disturbed areas. The
      species differed in their responses in different areas. Stage of incubation had
      little effect, except that late in incubation herring gulls returned to the nest
      more quickly. Weather variables affected responses of great black-backed gulls.
      For both species the behaviours we scored when the experimenter approached the
      nest were correlated, as were those following departure, but there was no
      correlation between these two sets of responses. Our study provides evidence on
      the relationships among components of an alarm and escape response, and provides
      a measure of influence of human disturbance for two species of gulls. 

PMID- 24897680
TI  - Repeated post trial administration of vasopressin impairs subsequent Differential
      Reinforcement of Low rates (DRL) performance.
AB  - Twenty-six male rats, maintained on a 23-h food deprivation regime, were trained
      on a DRL learning schedule. During pretraining (CRF) rats were placed in two
      groups according to speed in obtaining the criterion (good and poor learners).
      The performance of good and poor learners, injected with lysine vasopressin (LVP)
      immediately after each training session, was compared with that of control good
      and poor learners injected with saline. During the first DRL 20 stage, injected
      rats had fewer reinforcements than control rats. Fifty-five days later, during
      reacquisition of DRL 20, LVP rats again had fewer reinforcements, especially
      those which were formerly good learners in the CRF stage. Nonetheless, treated
      rats were able to shift their rate of responding from high to low frequency. A
      reduction of the minimal interresponse time to 16 s showed that LVP rats were
      able to adapt to this condition and that, in a further DRL 20 stage, the
      difference between the two groups was no longer significant. The results are
      discussed in terms of a modification of the behavioral expression of a learned
      response, without a specific action on memory processes. 

PMID- 24897681
TI  - Inhibition training in wolves and dogs.
AB  - A theoretical model previously proposed by the first author hypothesizes that
      dogs (C. familiaris) should perform better than wolves (C. lupus) on training
      tasks in which (1) cues are arbitrarily selected by the experimenter, (2)
      reinforcement is administered by the experimenter, and (3) the to-be-learned
      behavior has no perceptible, functional connection with the reinforcement. To
      test this hypothesis, four Eastern wolf pups (C. l. lycaon) and four Alaskan
      Malamute pups (C. familiaris) were administered a passive inhibition task at
      seven weeks of age and an active inhibition test (leash training) at 11 weeks of
      age. Significant differences in the predicted direction were obtained for all
      task variables. 

PMID- 24897682
TI  - Ontogenetic changes and the stability of rhesus monkey dominance relationships.
AB  - Dominance relationships were studied in a rhesus monkey group during five
      consecutive years. The group consisted of eight stable matriarchies and an adult
      male class which was replaced at the start, and again at the midpoint, of the
      study. Immature males were selectively harvested to maintain a sex ratio typical
      of natural troops. Maximum group size during the study was 77 animals. Dominance
      relationships were remarkably stable, with only 4.4% of dyads failing to show
      unidirectional relationships. Despite this stability, a linear ranking of all
      group members was not possible. Male dominance relationships with other males
      were among the most stable, following the fighting which ensued on male
      introductions. Male introductions did not disrupt female dominance relationships.
      Adult female dominance relationships were also quite stable, but immature females
      slowly achieved dominance over older sisters and females subordinate to their
      mothers. Such reversals were the result of processes lasting over many months.
      Many dominance assertions occurred prior to puberty but a significant number
      occurred following sexual maturity. Maturing females did not reverse dominance
      relationships according to any particular hierarchial order and, as a
      consequence, many were subordinate to animals that were dominated by others that
      they dominated. Although there was an alpha male that was dominant to all animals
      in the group, adult females dominated most adult males. Adult males, however,
      often reciprocated aggression directed at them. They almost invariably threatened
      or countercharged aggressive immature animals regardless of matriarchial
      membership. Adult males dominated some adult and most young females, even in
      families containing matriarchs and adult females to which the adult males always
      submitted. The dominance relationships of young males were similar to those of
      their sisters, until puberty. Young males did not necessarily bypass adult males
      that their mothers outranked, and often failed to win against adult females that
      their mothers dominated. Adolescent female aggression against females is seldom
      interfered with by adult males, and females may actively aid one another against
      males. In contrast, the aggression of young males often elicits interference by
      adult males, and young males often become the targets of redirected aggression in
      the group. As a consequence, whereas young females rise in rank to positions
      adjacent to their mothers, adolescent males often suffer losses to animals that
      they had dominated as juveniles. 

PMID- 24897692
TI  - Effects of test age, line and sex on tonic immobility responses and social
      reinstatement behaviour in Japanese quail Coturnix japonica.
AB  - The tonic immobility (TI) response and social reinstatement (SR) behaviour (as
      assessed in a treadmill test) were measured in 1, 2, 4, 6 and 10 week old
      Japanese quail of lines selected for long (LTI) and short (STI) duration of TI
      weighted for independence from SR behaviour or high (HSR) and low (LSR) levels of
      SR behaviour weighted for independence from durations of TI. Irrespective of age,
      LTI line birds had the longest and STI line birds the shortest duration of TI.
      The duration of TI did not differ between the HSR and LSR lines. Levels of SR
      behaviour were always higher in HSR line birds than in birds of the LSR line. SR
      behaviour did differ significantly between the LTI and STI lines and was shown at
      levels intermediate between those of the HSR and LSR lines although pairwise
      comparisons of line differences were not necessarily significant. The age and sex
      of the birds did not influence the duration of TI but levels of SR behaviour were
      lower at 2 and 4 weeks than at other ages and males showed more SR behaviour than
      females. 

PMID- 24897693
TI  - Agressivite et competition entre deux femelles d'especes differentes, en presence
      d'un male conspecifique de l'une d'elles, chez des coleopteres Bathysciinae
      souterrains.

PMID- 24897694
TI  - The effect of scents on the territorial and aggressive behaviour of laboratory
      rats.
AB  - The majority of works found in the literature mention odours as an important
      factor in the development of social lines and the unleashing of aggressive
      behaviour, but very few authors have studied more deeply the role that these
      odours play, how they influence behaviour and what importance the variations of
      these marks of identity may have. In the present work we analyse social relations
      presented by laboratory rats (Rattus norvegicus, Wistar breed) in seminatural
      conditions, with special reference to behaviours of dominance, territorialism and
      aggressiveness, and the importance that these marks of odour play on these
      behaviours. For this purpose, different individuals (from the established
      colonies as well as intruders, both males and females and pups) were impregnated
      with the urine of other individuals and then observed to see whether differences
      existed in the aggressive behaviour shown towards the intruders by the alpha male
      of the colony. 

PMID- 24897695
TI  - Some critical determinants of the behaviour of rats in the elevated plus-maze.
AB  - The effects of daytime testing periods, repeated test exposures, and level of
      illumination were tested on the behavior of rats in an elevated plus-maze
      consisting of two open and two enclosed arms. Rats made significantly more
      entries into the open arms and spent significantly more time in the open arms
      when testing was carried out between 8 h and 12 h than when performed between 14
      h and 17 h. Repeated exposure to the test apparatus tended to reduce time spent
      by rats in the open arms, number of entries into the open arms and total
      locomotor activity. Finally, it was found that an increase of the level of
      illuminance was followed by a decrease of all behavioural parameters. Since
      conflicting results have been reported for drug treatments evaluated in the
      elevated plus-maze (e.g., for compounds acting at the 5-HT1A receptor), the
      present results, based on the experimental conditions used, provide one possible
      explanation for these discrepancies. 

PMID- 24897696
TI  - On the dynamics of behavior allocation between simultaneously and successively
      available reinforcer sources.
AB  - The assumption of constant rates of extraneous reinforcement during changes in
      explicit reinforcer rates made by Herrnstein (1970) must logically be incorrect.
      An alternative theory that suggests constant extraneous-schedule values, rather
      than reinforcer rates, is suggested. In a test of this theory, six pigeons were
      trained on multiple variable-interval schedules with either no alternative
      reinforcers available, or with various variable-ratio or variable-interval
      schedules of reinforcement arranged concurrently, in 26 experimental conditions.
      A modification of McLean and White's (1983) multiple-schedule model that assumed
      a constant extraneous variable-ratio schedule fitted the obtained data, and those
      from two previous experiments, well. However, the model is dynamic, and allows
      the subject a range of adaptations to variations in arranged reinforcer rates. It
      is argued that this range of adaptations is both appropriate and necessary. 

PMID- 24897697
TI  - Diet selection by common shrews Sorex araneus in a depleting environment.
AB  - Common shrews (Sorex araneus L.) were presented with two prey types at various
      densities in a depleting environment. Observed diet choice was compared to
      predictions of the classical optimal diet model and of "shrew-specific"
      simulations incorporating patch depletion. Two strategies were simulated:
      expansion of the diet from taking only profitable prey to taking both types, and
      fixed partial preference. The simulations predict partial preference over a
      narrow range of initial densities of profitable prey. However, within this range,
      energetic benefits are relatively insensitive to diet composition. Shrews
      preferred more profitable prey and were more selective when encounter rate with
      profitable prey was higher, broadly as predicted by all the models. Partial
      preference was observed, but neither of the mechanisms simulated was strongly
      supported by results for the shrews. Univariate and multivariate analyses were
      used to identify cues involved in selecting prey. Instantaneous measures of
      encounter rates and encounters per unit search distance were the best predictors
      of subsequent prey choice, but decisions appear to have been made on a
      probabilistic basis. 

PMID- 24897698
TI  - Les modalites de communication dans le comportement sexual de Calliphora
      vomitoria (Diptera: Calliphoridae): vers une interpretation de la parade.
AB  - During sexual behaviour, the body and the behaviour of the partner provide a
      pattern of distant or contact signals. In order to evaluate in which respect
      courtship behaviour and its success depend on the comparison between the male's
      expectancy (template) and its actual perception, we have presented to male flies
      partner bodies with modified odours or shapes or both from different sexes and
      ages. Our data demonstrated the simultaneous use of different sensory channels.
      They suggest two different processes which might be involved in the construction
      of the template. Firstly, it could result from sensory reafferences, with a
      shuttle between stimuli and responses. In that case, the mismatch between
      expectancy and actual perception might induce disturbances in the courtship
      behaviour. If the differences are too high, it could stop the courtship sequence
      which resumes at its beginning. Secondly, the template could result from a
      process of representation. Then, when expectancy does not fit the perceived
      image, courtship would not be disturbed and the male could extract a new
      significance from the network of stimuli provided by the partner's body. 

PMID- 24897699
TI  - Foraging behaviour in guinea pigs: further tests of the marginal value theorem.
AB  - We studied the foraging behaviour of guinea pigs (Cavia porcellus) in laboratory
      environments with a single patch type. Six experiments were designed to test
      predictions of the marginal value theorem (MVT) for various foraging problems in
      a constant physical setting. In Part one (experiments I, I', and II) we used
      patches with resource depression. In experiment I there were two treatments,
      which differed in the function relating cumulative food gain to time in the
      patch. Experiment I' was a replicate of experiment I with greater differences in
      patch quality between treatments. In experiment II the treatments differed in the
      travel requirement between patches, while the patch gain function remained the
      same throughout. In experiments III, IV and V (Part two) there were patches with
      linear gain function and sudden exhaustion, and two treatments in each
      experiment. The treatments differed in prey encounter rate, maximal number of
      prey per patch, and travel time, respectively. In the six experiments the MVT
      predictions for prey per patch visit were qualitatively supported by the
      experimental results, and in most cases the quantitative fit was also good.
      Giving up times were longer than predicted. We conclude that the hypothesis of
      rate maximization, in spite of failing to predict some aspects of the results,
      provides a suitable framework for examining the foraging behaviour of this
      species. 

PMID- 24897706
TI  - Circadian rhythm of self-exposure to light in the golden hamster.
AB  - Golden hamsters were maintained in constant darkness with free access to a
      running wheel and to a lever that they could press to turn on the lights. The
      animals exhibited a circadian rhythm of lever pressing (and, therefore, of self
      exposure to light) in synchrony with the rhythm of running-wheel activity.
      Although most light exposure occurred during early subjective night (when single
      light pulses are known to cause phase delays of circadian rhythms), there was no
      significant difference between the circadian periods before and after the animals
      were allowed to self-stimulate. It is suggested that the conservation of
      circadian period was due to a reduction in photic sensitivity caused by the
      observed pattern of light exposure (multiple brief pulses rather than single long
      pulses). 

PMID- 24897707
TI  - Kinetic dialogs in predator-prey recognition.
AB  - Kinetic dialogs are presented in this paper, which may help to decipher ambiguous
      stimuli during interactions of individuals that possess extremely antagonistic
      interests, such as predators and prey. Predators and prey tend not to be
      perceived by one another because natural selection penalizes any signal that
      announces their presence. Therefore, available signals for making adequate
      decisions may be scarce. I propose that within this impoverished signalization
      system the way each party reacts to a sudden movement of the other, strongly
      depends upon its own ongoing condition of motion immediately before the movement
      is perceived. The proposed signalization system is based on the temporal
      correlation of movements of the parties (contingency) and on sign (approach
      withdrawal). If, after the animal moves, an object approaches, it should flee.
      But if the object withdraws, it should attack. I studied the behaviour of a fish
      (Brachydanio rerio) in response to a simple stimulus that approached or withdrew
      contingently with the fish movements. This was accomplished by means of a closed
      loop system in which the movements of the fish swimming in a glass tank were
      detected by a high-speed video camera connected to a computer. A real-time
      operating algorithm kept track of the movements of the fish. When movement was
      detected, a 4 mm clay ball was directed towards (predator program), or withdrawn
      from (prey program), the fish. Two different measurements of the 'antipredator'
      behaviour tested (i.e., frequency of turns after the stimulus and number of halts
      per stimulus) showed significantly higher values under the approaching condition
      than under the withdrawing condition. This differential reaction of the fish to
      two different values of the predator/prey variable suggests that specific
      predator/prey channels of communication are being manipulated with this method. 

PMID- 24897708
TI  - Hippocampal electrical activity in rabbits during exploration of a semi-natural
      environment.
AB  - The hippocampal EEG shows characteristic profiles during different behavioural
      items. A class of hippocampal neurones is active when the animal is in specific
      places of an environment (place units). However, there are only a few neurones
      and the role of the hippocampal EEG in spatial information processing remains to
      be explained. In the present experiment we studied the exploratory behaviour of
      rabbits (implanted with chronic electrodes in the hippocampus) in an open-air,
      semi-natural environment. Hippocampal EEG was recorded by telemetry and related
      to exploratory behaviour by superimposition onto video. Six rabbits were
      introduced singly to the semi-natural environment and each remained there for 3
      days. Their behaviour and EEG was analysed for three 30 min sessions (at 0, 6 and
      56 h). Exploration was the main behaviour in the first observation and decreased
      progressively in the following sessions. The environment was divided into three
      zones which were explored differently through time. The hippocampal EEG, recorded
      during exploration, presented an increase of frequency from the first to the
      second observation. However, since EEG frequency increased when the animal
      explored the central area of the enclosure, a response in the place domain cannot
      be excluded. 

PMID- 24897709
TI  - Unexpressed morphine conditioned salt aversion: procedural variants and
      hypertonicity of salt.
AB  - Previous work has demonstrated that rats that received a sodium chloride (salt)
      solution paired with a high dose of morphine do not directly express a
      conditioned salt aversion (decreased intake) in a one-bottle test. Importantly,
      lithium conditioned salt aversions and morphine conditioned saccharin aversions
      are readily expressed. The present study examined two possible accounts of the
      failure for morphine conditioned salt aversion to be directly expressed.
      Experiment 1 eliminated an account based on procedural variations that were
      uncontrolled in the original salt and saccharin conditioning protocols (Bevins et
      al., 1996). Experiment 2 eliminated a hypertonic account that argues that the
      high concentrations of salt in the previous work (1% and greater) interfered with
      direct expression of salt aversion by inducing continual drinking. Rats given a
      non-hypertonic salt solution (0.3%) paired with morphine still did not express a
      salt aversion in a one-bottle test. A two-bottle testing procedure, however,
      revealed a robust salt aversion with the non-hypertonic solution. 

PMID- 24897710
TI  - Choice of timeout from fixed-time schedules: Comparison of two procedures.
AB  - Four rats obtained food on fixed-time (FT) 1-, 4-, and 16-min schedules. During
      FT schedules, a lever press produced a timeout period during which food could not
      be delivered. When timeout was in effect, a lever press ended the timeout period
      and reinstated the FT schedule. In different conditions, the timing of the FT
      interval either stopped for the duration of the timeout period (Stop condition)
      or the timing of the FT interval continued during timeout (No Stop condition).
      The percentage of session time spent in timeout periods increased as the time
      between food deliveries increased regardless of whether or not timing of the FT
      interval stopped during timeout. The timeout percentage was larger on Stop than
      No Stop conditions if the obtained interfood interval was also longer. The rate
      of initiation of timeout periods tended to increase from FT 1-min to FT 4-min
      schedules, and then not increase further or decrease on FT 16-min. The mean time
      per timeout period tended to be similar on FT 1- and FT 4-min schedules and then
      increase on FT 16-min. A given percentage of session time spent in timeout
      periods appears to be due to interactions between rate of timeout, duration of
      timeout periods and interfood interval. The data are not consistent with the
      suggestion that timeout initiation represents escape from aversive aspects of
      intermittent reinforcement. Instead, choice of timeout shares some of the
      properties of facultative behaviors. 

PMID- 24897711
TI  - On systems of reference involved in spatial memory.
AB  - The system of reference used by an animal for memorizing the location of a hidden
      place to which it is liable to return (the goal) can be theoretically defined as
      being 'self-centred', 'local', or 'overall'. According to the system of
      reference, the goal location is memorized by means of: (1) an egocentric coding
      that specifies the direction and distance to the goal with respect to the
      animal's current position; (2) an exocentric coding that specifies the apparent
      configuration of nearby landmarks as perceived from the goal; or (3) an
      exocentric coding based on a global representation of space over the whole range
      of movement, respectively. A compass provides useful directional information (to
      the species capable of deriving it) that may be used in the framework of any of
      the three systems of reference. A goal location may be memorized concurrently in
      the three systems of reference which are complementary rather than mutually
      exclusive. In particular, the joint use of the self-centred and local systems of
      reference has been demonstrated in animals of numerous species that are able to
      shift from the former to the latter while approaching a goal. In contrast, there
      is no clear evidence supporting that an animal is able to rely on a global
      representation of space. 

PMID- 24897712
TI  - Conditional time-place learning.
AB  - Encoding the spatial location and the time at which significant biological events
      occur is thought to be a fundamental way in which memory is organized in animals.
      Some field data on gulls' foraging behavior suggests that time-place behavior may
      consist of a conditional discrimination. In this study gulls flew at sunrise to
      locations containing earth worms, but only after rainfall. The purpose of the
      present research was to attempt to demonstrate conditional time-place learning in
      the laboratory. Pigeons were trained to visit three sites successively in two
      different orders that were signaled by room and test chamber cues. The pigeons
      successfully learned the task, supporting the notion that time-place foraging
      behavior can be modulated by other environmental regularities. 

PMID- 24897713
TI  - Male rank and female choice in the bank vole, Clethrionomys glareolus.
AB  - This study aims to determine whether bank vole females selectively prefer the
      odour of a dominant male over that of a subordinate. The dominance rank of males
      was established by their aggression. The males that were considered dominants had
      higher aggression scores, measured as the sum of the number of attacks and
      pursuits. Dominants had sex accessory glands weighing significantly more than
      those of the subordinates, as a consequence of their higher plasma testosterone
      levels. In a two-choice test, naive females were more attracted to dominant males
      than to subordinates as manifested by the females' higher level of activity, more
      sniffs, and more time spent sniffing males of high rank. The same pattern of
      differences was noted when urine of dominant and subordinate males was used. The
      study provides some information about the female role in mate selection. 

PMID- 24897714
TI  - Progressive ratio performance varies with body weight in rats.
AB  - The progressive ratio (PR) performance of male rats was assessed under varying
      states of food restriction (75-100% of free-feeding body weight). Because
      performance of this task requires subjects to increase, within each session, the
      amount of effort (lever presses) expended for subsequent food reinforcers, it is
      thought that measures of performance in this task provide an index of
      'motivation' to work for food. In earlier studies, subjects were 'prefed' their
      daily food allotments at a variety of intervals (0.25-6 h) prior to PR testing.
      In those studies, it was determined that such feeding episodes did not
      significantly affect PR performance and thus, motivation to work for food. The
      present studies demonstrate that PR behavior varies significantly as a function
      of body weight. Thus, in the rat, body weight per se has a greater influence over
      food-related satiety than does the recent ingestion of a meal. 

PMID- 24897715
TI  - Bubbleblow in beluga whales (Delphinapterus leucas): a play activity?
AB  - In Odontocetes, bubbleblow is reported in several ethograms but its function is
      poorly understood. For the five captive beluga whales (Delphinapterus leucas) of
      the Vancouver Public Aquarium, we recorded the occurrence of this behaviour, its
      diurnal pattern and individual variability. We suggest that bubbleblow can be
      considered as a solitary play activity. 

PMID- 24897716
TI  - Development of early social behaviour of rainbow trout, Salmo Gairdneri (Pisces,
      Salmonidae).
AB  - Young rainbow trout do not begin agonistic behaviour until they are free
      swimming. Agonistic behaviour initially consists mostly of simple,
      straightforward attacks. More complex threat patterns are added with increasing
      age. Increased water flow rate promotes station-holding and apparently
      territorial behaviour, especially at low fish densities. High fish densities lead
      to an increase in agonistic interactions, especially in fast flowing water. The
      interplay of these factors with the developmental processes of social behaviour
      is discussed. 

PMID- 24897717
TI  - Quantitative studies on the elicitation of the electrodermal response by calls
      and synthetic acoustical stimuli in Rana Lessonae camerano, Rana R. Ridibunda
      pallas and the hybrid Rana "Esculenta" L. (Anura, Amphibia).
AB  - The thresholds of the electrodermal response (EDR) were determined for the
      European water frogs Rana lessonae, Rana ridibunda ridibunda, and their hybrid,
      Rana "esculenta". Both males and females were tested, during and outside the
      calling period. The stimuli used were the mating, territorial and release calls
      of all three phenotypes, as well as synthetic acoustical stimuli having the same
      impulse pattern but differing in frequency. The EDR could be elicited by all the
      calls tested, and by the synthetic acoustical stimuli at frequencies between 100
      and 4000 Hz. Below ca. 1000 Hz the thresholds of the smaller Rana lessonae were
      higher than those of the bigger Rana ridibunda, while the relations were reversed
      above 1000 Hz. During the calling period the highest thresholds, in all three
      phenotypes, were those to the conspecific mating call. The synthetic stimulus at
      the dominant frequency of the mating call elicited the EDR only at sound
      pressures considerably higher than those of an effective synthetic stimulus at
      the dominant frequency of the territorial call. The thresholds to the territorial
      and release calls during the calling period were only slightly different from
      those at other times. Those to the mating call and to the synthetic stimulus at
      the dominant frequency of the mating call, however, were significantly lower than
      during the calling period. For each phenotype, the stimulus exhibiting the
      greatest seasonal fluctuation in threshold was the conspecific mating call. 

PMID- 24897718
TI  - Mating call discrimination by females of the treefrog Hyla Meridionalis on
      Tenerife.
AB  - Mating behavior of Hyla meridionalis was observed at an artificial reservoir in
      Punta del Hidalgo, Tenerife. Playback experiments were conducted in the field
      near the reservoir. The density of calling males was extremely high, and
      individuals sometimes called within 5 cm of each other. Males often changed
      calling positions and successfully attempted to clasp one another. Gravid females
      were common and most often found in amplexus. In three of four observations, the
      male initiated amplexus from a distance of 5 to 10 cm. Only 11 of 107 gravid
      females responded in two-choice playback experiments. Ten chose the calls of a
      conspecific male recorded at Punta del Hidalgo, and one female chose the calls of
      a male of H. a. arborea recorded in Germany. Our observations and experimental
      results are compared with those of similar studies of North American hylids. 

PMID- 24897719
TI  - The effects of wulst lesions on simple visual discrimination performance in the
      pigeon.
AB  - Pigeons with lesions involving the hyperstriatum accessorium, hyperstriatum
      intercalatus superior and hyperstriatum dorsale were compared with sham operated
      controls on acquisition of a simple colour/brightness discrimination. Correct and
      incorrect choices together with choice latencies were recorded. The lesioned
      birds' performance on the discrimination aspects of the task was not inferior to
      controls. However, the choice times of the lesioned group were significantly
      longer than controls. The within session pattern of choice latencies was also
      significantly different, with the lesioned birds beginning each session with
      longer latencies than controls but ending the session with choice latencies
      equivalent to controls. The lesion effect is attributed to damage to a mechanism
      concerned with arousal or response facilitation within the anterior Wulst. 

PMID- 24897720
TI  - Responses of male and female domestic chicks to a startling stimulus and the
      effects of a tranquilliser.
AB  - The present study examined sex differences in the responses of domestic chicks to
      novelty and exposure to a startling stimulus. In the first experiment, 7-day-old
      male and female chicks were placed individually in a novel environment for 10-min
      periods. After 5 min, half of the chicks were exposed to a loud bell. Males
      showed more passive behaviour such as freezing, sitting and eye-closure and were
      less active and less vocal than females, both before and after exposure to the
      bell. Ringing the bell increased immobility and reduced activity and vocalisation
      in both sexes thus confirming its effectiveness as a fear-elicitor. The second
      experiment involved injecting males and females with either a tranquilliser
      (Pacitran) or water. Immobility decreased whereas peeping and walking increased
      in the Pacitran-injected groups both before and after the bell was rung. The
      behaviour of untranquillised, water-injected females was comparable to that of
      Pacitran- treated males. These results may reflect sex differences in either the
      form of fear responding or the underlying levels of fearfulness; the latter seems
      more likely. 

PMID- 24897721
TI  - Feeding behaviour of domestic chicks in a novel environment: Effects of food
      deprivation and sex.
AB  - Sex differences in responses to novelty with particular reference to feeding
      activity were examined in the present study. Male and female domestic chicks (7-
      and 8-days-old) were observed in a modified home cage and in an open field or
      novel environment after experiencing either deprivation of food or continuous
      access to food. Previous reports that females show more activity and vocalisation
      and less sitting and eye-closure than males in fearful situations were confirmed
      in the tests with no deprivation but these sex differences were distorted in the
      deprivation tests by high feeding actibity. Following deprivation of food,
      females fed sooner and fed more than males both in the home cage and the open
      field. These results provide further evidemce that the female chick is less
      fearful than the male. The relevance of the hypothesis that behavioural
      persistence is increased by testosterone and its theoretical implications
      regarding normal sex differences in behaviour are questioned because, in fact,
      females showed longer feeding bouts than males. It is suggested that persistence,
      of feeding at least, in young chicks is not influenced by natural levels of
      androgens. 

PMID- 24897722
TI  - The behaviour of adult male Long-Evans rats Rattus norvegicus toward pups of
      different ages.
AB  - Adult male Long-Evans rats were presented with 1-7 or 14-21 day old pups for 20
      days. Pups were changed every 12 h and each male received pups from three
      litters, with litters changed every week. Pup-related activities were observed
      for two 15-min periods each day. Males with young pups had a shorter latency to
      crouch over and carry pups while males with older pups showed a shorter latency
      to lick pups. Males with young pups had higher nest ratings, and engaged in more
      nest building, crouching over and carrying pups than males with older pups, while
      males with older pups spent more time touching, sniffing, and licking pups. Both
      groups of males showed an increase in pup-related behaviour over the first 8-10
      days of pup exposure and a decrease in pup-related behaviour when the litters
      were changed. These results indicate that pup age is an important factor in
      determining male behaviour. Males direct parental behaviour toward neonatal pups
      and affiliative behaviour toward older pups. The importance of affiliative
      behaviour with adult males in the social development of juvenile rats is
      discussed. 

PMID- 24897723
TI  - Why do distress calls evoke interspecific responses? An experimental study
      applied to some species of birds.
AB  - Distress calls of birds are well-known to elicit interspecific responses when
      they are broadcast to different species. We suggest that the interspecificity
      phenomenon results from the use of similar laws of decoding by all species. To
      support this hypothesis, we broadcast a simplified synthetic call to five species
      of birds (Larus argentatus, L. ridibundus, Vanellus vanellus, Corvus frugilegus
      and Sturnus vulgaris). This synthetic call was built by keeping all the
      parameters involved in the process of recognition and common to the different
      species and by removing species specific markers. No significant differences were
      found between this signal and specific control signals (one for each species).
      These results support the hypothesis that the interspecificity of responses is
      linked to similarities in the process of identification of the distress message.
      In addition, the decoding law of such calls appears to conform to selection
      pressures imposed by physical laws of sound transmission at long range. 

PMID- 24897724
TI  - The agonistic behaviour of Pimelodella kronei, a troglobitic catfish from
      Southeastern Brazil (Siluriformes, Pimelodidae).
AB  - Blind pimelodid catfishes Pimelodella kronei from a karstic area in Southeastern
      Brazil, were paired in the laboratory to study the agonistic behaviour. P.
      kronei, a recent troglobite, displays an intense and complex aggressive
      behaviour, presenting dominance based primarily on size. This dominance is
      established after bouts of duration inversely proportional to the size difference
      between the opponents. The aggressive repertoire of these pimelodids is similar
      to that of other studied siluriforms, and consists of varied and articulate
      components that include oscillations, shoves and bites. Once dominance is
      established, the subordinates recognize and avoid immediately the dominants after
      body contact or close proximity. High level of aggressivity in the blind
      catfishes may be related to competition for food in the cave habitat, where
      agonistic interactions were frequently observed. 

PMID- 24897725
TI  - Acoustic behaviour of Ephippiger ephippiger fiebig (Orthoptera, Tettigoniidae)
      within a habitat of Southern France.
AB  - Field studies on the bushcricket Ephippiger ephippiger reveal that the males are
      highly mobile during their daily activity period. The distribution pattern of
      males is affected by the vegetation of the habitat. Males are clumped in areas
      with Sarothamnus scoparius (broom). The distribution implies the state of a fluid
      balance within the population. In the habitat the stridulatory period of males is
      influenced by climatic conditions. Singing is completely inhibited at a
      temperature below 17 degrees  C, during strong wind and rain. Thus, mating
      success and frequency is strongly affected by these biotic factors.
      Investigations in the laboratory show that constant ambient temperatures do not
      influence the daily stridulatory period; acoustically isolated females show a
      daily period of high locomotory activity nearly synchrone to the male
      stridulatory period. 

PMID- 24897726
TI  - Positional choices and visual discrimination in non-delayed appetitive
      discrimination tasks in mice.
AB  - Mice were submitted to visual discrimination learning using a large choice
      compartment positioned in front of two adjacent runways, black and white, one of
      which was baited. Rate of acquisition, expressed by the mean number of sessions
      to criterion did not differ between the initial task and two reversals. However,
      the number of correct choices before criterion was significantly lower on both
      reversals compared to original learning. Position habit rates did not vary
      significantly between acquisitions, and they were negatively correlated with
      visual discrimination rates in the three learning phases. This observation, and
      the fact that on each phase, position habits were largely absent on initial
      sessions and only developed gradually, suggest that position habits may occur
      when animals do not grasp the solution to the visual task. 

PMID- 24897727
TI  - Effect of post-weaning social experience with normal females on the behaviour of
      adult male staggerer mice interacting with normal females.
AB  - Adult male staggerer mice reared under standard conditions display no sexual
      behaviour. When maintained for a time with normal female mice however 5% of the
      mutant males were able to copulate. We hypothesized that the effects of such
      social experience would be revealed most clearly by changes in the pattern of
      male behaviour. Two groups of mutant males were subjected to different social
      experience after weaning. One group was maintained with normal female mice and
      the other with staggerer mutant females. There were differences between the two
      groups in the frequency, duration and temporal organization of interactions
      between mutant males and normal females. Social experience with normal females
      modified male behaviour, producing greater synchrony with female behaviour and a
      reduction in stereotypic behaviours such as scratching. 

PMID- 24897734
TI  - 125 Years and Counting.

PMID- 24897735
TI  - Surgical Site Infections in Orthopaedic Surgery Demonstrate Clones Similar to
      Those in Orthopaedic Staphylococcus aureus Nasal Carriers.
AB  - BACKGROUND: Staphylococcus aureus is the main microbial pathogen in orthopaedic
      infections, and it adds considerable extra costs to the national health-care
      system each year. Nasal carriers of Staphylococcus aureus have an increased risk
      of invasive disease, including surgical site infection. The purpose of the
      present study was to investigate whether the Staphylococcus aureus carrier clones
      found in patients undergoing elective orthopaedic surgery were the same as the
      clones found in isolates from orthopaedic patients with Staphylococcus aureus
      surgical site infections. METHODS: Patients admitted for elective orthopaedic
      surgery underwent nasal cultures for Staphylococcus aureus. Further, orthopaedic
      patients with a deep surgical site infection caused by Staphylococcus aureus were
      characterized using the same genotyping methods: multilocus sequence typing and
      staphylococcal protein A typing. RESULTS: Multilocus sequence typing revealed a
      large number of genotypes in the two populations. However, 85% of nasal carriers
      and 90% of surgical site infection isolates could be classified into the same
      four multilocus sequence typing clonal complexes. The risk of Staphylococcus
      aureus surgical site infection in nasal carriers compared with non-carriers was
      5.8 times higher (95% confidence interval, 1.5 to 23.1 times). Of the nasal
      carriers, 6.3% (95% confidence interval, 1.7% to 10.9% [seven of 111 patients])
      developed a deep Staphylococcus aureus surgical site infection, and all but one
      patient had identical genotypes in the nasal and surgical site infection
      isolates. CONCLUSIONS: Staphylococcus aureus isolates from nasal carriers and
      patients with surgical site infection clustered into the same few multilocus
      sequence typing clonal complexes. This finding confirms the existence of some
      commonly occurring Staphylococcus aureus clones in different population groups
      within a geographically restricted area. The almost complete individual
      concordance between Staphylococcus aureus genotypes in carriers who developed a
      deep surgical site infection strongly supports transmission from the nose, skin
      surfaces, and other endogenous body regions as a possible route. CLINICAL
      RELEVANCE: Surgical site infections might be more frequently caused by endogenous
      transmission than was previously assumed. Perioperative preventive efforts must
      focus more on this route to further decrease the risk of postoperative
      orthopaedic infections.

PMID- 24897736
TI  - Simultaneous Bilateral or Unilateral Carpal Tunnel Release? A Prospective Cohort
      Study of Early Outcomes and Limitations.
AB  - BACKGROUND: Over 60% of patients with carpal tunnel syndrome present with
      symptoms and findings of nerve compression in both hands. Our goal was to compare
      patient-rated difficulties in performing activities of daily living in the early
      postoperative period between those undergoing bilateral carpal tunnel release and
      those undergoing unilateral carpal tunnel release. METHODS: This prospective
      cohort study enrolled consecutive patients with bilateral carpal tunnel syndrome
      undergoing bilateral carpal tunnel release (n = 47) or unilateral carpal tunnel
      release (n = 41). Patient function and disease severity were measured by an
      abbreviated form of the Disabilities of the Arm, Shoulder and Hand questionnaire,
      QuickDASH, and the Boston Carpal Tunnel Questionnaire at baseline, at
      postoperative visit 1 at a mean time (and standard deviation) of 10 +/- 3 days,
      and at postoperative visit 2 at a mean time (and standard deviation) of 30 +/- 6
      days. Patients rated their difficulty in completing fifteen activities of daily
      living each day for the first postoperative week. Patients reported the factors
      that influenced their choice of surgery. RESULTS: There was no difference in
      baseline function or disease severity between the two groups with regard to
      QuickDASH and the Boston Carpal Tunnel Questionnaire. Patients in both groups
      improved after carpal tunnel release with no difference between groups either at
      postoperative visit 1 for QuickDASH (p = 0.97) and the Boston Carpal Tunnel
      Questionnaire (p = 0.86) or at postoperative visit 2 for QuickDASH (p = 0.43) and
      the Boston Carpal Tunnel Questionnaire (p = 0.34). Patients undergoing bilateral
      carpal tunnel release had more difficulty only during postoperative days 1 to 2
      in opening jars (p = 0.03), cooking (p = 0.008), and doing household chores (p =
      0.02). Patients in the two groups did not differ (p > 0.05) in their abilities to
      perform activities of daily living necessary for personal hygiene or independence
      on any day during the first seven days following surgery with regard to using the
      bathroom, bathing, dressing, or eating. Although the most common reason why
      patients chose bilateral carpal tunnel release was to avoid two surgical
      procedures (42%), the most common reason why patients chose unilateral carpal
      tunnel release was concern for self-care (36%). CONCLUSIONS: Patients with
      bilateral carpal tunnel syndrome can anticipate more severe functional impairment
      during the first few postoperative days with bilateral carpal tunnel release
      compared with unilateral carpal tunnel release, but limitations beyond
      postoperative day 2 or 3 are similar for bilateral and unilateral carpal tunnel
      release. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 24897737
TI  - Early Surgical Decompression Restores Neurovascular Blood Flow and Ischemic
      Parameters in an in Vivo Animal Model of Nerve Compression Injury.
AB  - BACKGROUND: Chronic nerve compression neuropathies result in decreased blood flow
      at the site of compression. Surgical decompression of the nerve often has
      variable postoperative results. The current study examines whether the timing of
      surgical intervention is an important variable in reversing the compression
      induced ischemia and associated changes in biochemical markers. METHODS: An
      established model of chronic nerve compression injury was created in 100 C57BL/6
      mice, and serial electrophysiological examinations were used to confirm the
      creation of a chronic nerve compression injury. Laser speckle imaging was used to
      measure neural blood flow. Nerves in the animals that did not undergo
      decompression were harvested at two, four, and six weeks after injury and
      analyzed for hypoxia-inducible factor 1alpha (HIF1alpha), catalase, superoxide
      dismutase (SOD), and matrix metalloproteinases (MMPs) 2 and 9. Surgical
      decompression in other animals was performed at either an early (two-week) or
      late (six-week) time point after injury, with specimens harvested at multiple
      time points after decompression. One-way analysis of variance with Bonferroni
      correction was performed. RESULTS: Chronic nerve compression injury initially
      induced hyperemia (1.37 +/- 0.50 times that in the contralateral, uninjured
      nerve) followed by a decline in neural blood flow by four weeks (0.66 +/- 0.14, p
      = 0.0313). In parallel, HIF1alpha, catalase, and SOD were elevated early after
      compression, whereas extracellular matrix-altering proteins were elevated later
      in the disease. Although early decompression yielded a return of blood flow to a
      hyperemic state (1.35 +/- 0.16, p = 0.0057), late decompression did not result in
      reversal of the abnormal neurovascular flow. With late decompression, an MMP9
      mediated structural alteration of the extracellular matrix was seen, producing
      irreversible changes in blood flow parameters. Although nerve conduction velocity
      measurements returned to normal two weeks after decompression irrespective of the
      timing of the surgical intervention, distal latency returned to normal only after
      early decompression (0.97 +/- 0.06 msec compared with 1.22 +/- 0.06 msec for late
      decompression, p = 0.009). CONCLUSIONS: Chronic nerve compression injuries
      decreased neurovascular flow and induced ischemia by upregulating HIF1alpha,
      catalase, and MMP9. Early surgical intervention offered better return to normal
      electrophysiological parameters compared with late intervention. CLINICAL
      RELEVANCE: These data present a clinical correlate to the variable functional
      outcomes seen following surgical release of chronic nerve compression injuries
      and provide early support for using distal latency as a predictor of outcomes
      following surgical release.

PMID- 24897738
TI  - Early Patient Outcomes After Primary Total Knee Arthroplasty with Quadriceps
      Sparing Subvastus and Medial Parapatellar Techniques: A Randomized, Double-Blind
      Clinical Trial.
AB  - BACKGROUND: Techniques that reduce injury to the knee extensor mechanism may
      cause less pain and allow faster recovery of knee function after primary total
      knee arthroplasty. A quadriceps-sparing (QS) subvastus technique of total knee
      arthroplasty was compared with medial parapatellar arthrotomy (MPPA) to determine
      which surgical technique led to better patient-reported function and less
      postoperative pain and opioid utilization. METHODS: In this prospective, double
      blind study, 129 patients undergoing total knee arthroplasty were randomized to
      the QS or the MPPA group after skin incision. All surgical procedures utilized
      minimally invasive surgery principles and standardized anesthesia, implants,
      analgesia, and rehabilitation. The Knee Society Score (KSS) was obtained at
      baseline and one and three months after surgery. Weekly telephone interviews were
      used to collect patient-reported outcomes including ambulatory device use, the
      UCLA (University of California Los Angeles) activity score, performance of daily
      living activities, and opioid utilization. RESULTS: No differences between groups
      were seen in opioid utilization, either during the acute hospitalization or in
      the eight weeks after surgery. The QS group reported significantly less pain at
      rest on postoperative day one and with activity on day three (p = 0.04 for each).
      Compared with baseline, both groups showed significant improvements in the KSS at
      one month (MPPA, p = 0.0278; QS, p = 0.0021) and three months (p < 0.0001 for
      each) as well as week-to-week gains in walking independence through five weeks
      after surgery. Independence from ambulatory devices outside the home lagged
      behind independence indoors by about two weeks in both groups. CONCLUSIONS: When
      primary total knee arthroplasty was performed with contemporary minimally
      invasive surgery principles and standardized implants, anesthesia, and
      postoperative pathways, the QS technique yielded no significant early functional
      advantages or differences in opioid utilization compared with the MPPA technique.
      However, the mean pain scores reported by patients in the QS group were slightly
      lower at rest on postoperative day one and during activity on day three. LEVEL OF
      EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24897739
TI  - Routine Examination of Pathology Specimens Following Knee Arthroscopy: A Cost
      Effectiveness Analysis.
AB  - BACKGROUND: While the clinical value of routine pathologic examination of tissues
      removed during orthopaedic procedures has not been determined, limited cost
      effectiveness and a low prevalence of findings that alter patient management have
      been previously demonstrated with arthroscopy. The purpose of this study was to
      examine the clinical value and cost-effectiveness of routine histological
      examination of knee arthroscopy specimens. METHODS: Retrospective chart analysis
      of 3797 consecutive knee arthroscopies by two surgeons from 2004 to 2013 at three
      affiliated hospitals within one health-care system was undertaken. Pathology
      reports regarding tissue removed during partial meniscectomies and anterior
      cruciate ligament reconstructions were reviewed to determine if the results
      altered patient care. The total costs of histological examination were estimated
      in 2012-adjusted U.S. dollars. The cost per health effect was determined by
      calculating the cost per discrepant and discordant diagnosis. RESULTS: The
      prevalence of concordant diagnoses was 99.3% (3769 of 3797), the prevalence of
      discrepant diagnoses was 0.7% (twenty-seven of 3797), and the prevalence of
      discordant diagnoses was 0.026% (one of 3797). The total cost of histological
      examinations was estimated to be $371,810. The total cost of the pathology cost
      per discrepant diagnosis was $13,771, and the cost per discordant diagnosis was
      $371,810. CONCLUSIONS: Routine pathological examination of surgical specimens
      from patients undergoing knee arthroscopy had limited cost-effectiveness because
      of the low prevalence of findings that altered patient management. Histological
      examination of surgical specimens from arthroscopic knee surgery did not alter
      patient care and increased costs. We suggest that gross and histological
      examination of tissue removed during knee arthroscopy should be done at the
      discretion of the orthopaedic surgeon rather than being mandatory.

PMID- 24897740
TI  - The Role of Overweight and Obesity in Relation to the More Rapid Growth of Total
      Knee Arthroplasty Volume Compared with Total Hip Arthroplasty Volume.
AB  - BACKGROUND: The volume of primary joint replacements performed in the United
      States increased rapidly over the past twenty years, but the growth rate of total
      knee arthroplasties exceeded that of total hip arthroplasties. The aim of this
      study was to identify the key contributing factors behind this differential
      growth rate. METHODS: We compiled longitudinal data on total hip arthroplasty and
      total knee arthroplasty volume, length of hospital stay, and in-hospital
      mortality from the Nationwide Inpatient Sample; we calculated reimbursement using
      information available in the Federal Register and Centers for Medicare & Medicaid
      Services databases; we determined trends in body mass index from Behavioral Risk
      Factor Surveillance System findings; and we estimated the size of the surgical
      workforce based on membership data from the American Academy of Orthopaedic
      Surgeons. These sources each contained at least ten years of data, ending in
      2009. Data sources were analyzed and were compared to identify supply-side and
      demand-side factors contributing to the more rapid growth observed in total knee
      arthroplasty. RESULTS: Of the factors examined, body mass index played the most
      substantial role in increasing demand for total knee arthroplasty above that of
      total hip arthroplasty, with younger individuals affected to a greater degree.
      More rapid growth in utilization of total knee arthroplasty over total hip
      arthroplasty in individuals with a body mass index of >=25 kg/m2 was responsible
      for 95% of the differential increase in total knee arthroplasty over total hip
      arthroplasty volumes. Hospital and physician reimbursement, length of stay, and
      in-hospital mortality did not improve more for total knee arthroplasty than total
      hip arthroplasty. The surgical community responded to additional demand primarily
      by increasing per-physician output. CONCLUSIONS: Growth in total knee
      arthroplasty volume has far outpaced that of total hip arthroplasty among those
      with a body mass index of >=25 kg/m2 but not for those with a body mass index of
      <25 kg/m2. The magnitude of this effect will continue to expand if the proportion
      of Americans with a body mass index of >=25 kg/m2 continues to increase. Changes
      in hospital and physician reimbursement, length of stay, and in-hospital
      mortality did not contribute to this differential growth rate.

PMID- 24897741
TI  - Informed Decision-Making Regarding Amputation for Complex Regional Pain Syndrome
      Type I.
AB  - BACKGROUND: Literature on complex regional pain syndrome type I (CRPS-I)
      discussing the decision to amputate or not, the level of amputation, or the
      timing of the amputation is scarce. We evaluated informed decision-making
      regarding amputation for CRPS-I. METHODS: We describe our findings in a
      retrospective study of the decision-making process of thirty-six patients who
      underwent amputation for CRPS-I at our university medical center from 2000 to
      2012. Additionally, we present the incidents preceding the CRPS-I, the reasons
      for and the levels of the amputation, and the outcomes after the amputations.
      RESULTS: Team members and the patient decided together whether or not to amputate
      and the level of amputation. Issues such as level of pain or allodynia,
      infection, desired length of the residual limb, joint range of motion, strength
      of all extremities, ability to use walking aids, and psychological "green,
      yellow, and red flags" were weighed in this process. There were no complications
      during the amputation surgery, a 22% rate of complications (infection in all but
      one patient) immediately postoperatively (reamputation not required), a 72% rate
      of phantom pain immediately after or within the first three months after the
      amputation, and a 77% rate of phantom pain more than one year after the
      amputation. CONCLUSIONS: Informed decision-making regarding amputation for CRPS-I
      remains a complex process for which little evidence is available to support
      patient choices; patient-specific outcomes are not predictable. However,
      amputation should not be ignored as a treatment option for long-standing therapy
      resistant CRPS-I. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 24897742
TI  - Venous Thromboembolic Events After Spinal Fusion: Which Patients Are at High
      Risk?
AB  - BACKGROUND: Postoperative venous thromboembolic events (VTEs), which include
      pulmonary emboli and deep venous thromboses, are potentially preventable causes
      of death. The aim of this study was to investigate the patient and procedure
      related risk factors for the occurrence of VTEs in patients undergoing spinal
      fusion. METHODS: We used ICD-9-CM (International Classification of Diseases, 9th
      Revision, Clinical Modification) procedure codes to identify patients in the
      Nationwide Inpatient Sample (NIS) database for 2001 through 2010 who were treated
      with spinal fusion. The occurrence of a symptomatic VTE was identified with use
      of ICD-9-CM diagnosis codes. Patient demographics, hospital characteristics, and
      comorbidities in the VTE and non-VTE groups were analyzed, and independent risk
      factors for VTE were identified. RESULTS: A total of 710,154 spinal fusion
      procedures were identified in the NIS from 2001 to 2010, and 3525 (0.50%) of
      these patients were recorded as having 3777 VTEs, consisting of 2038 deep venous
      thromboses (0.29%) and 1739 pulmonary emboli (0.24%). Patients with a VTE were
      older on average (57.63 years compared with 52.88 years for patients without a
      VTE) and more often male (VTE incidence, 0.58% compared with 0.42% for female)
      and black (VTE incidence, 0.78% compared with 0.47% for white). Postoperative VTE
      occurrence was associated with a longer hospital stay (18.0 compared with 3.94
      days) and higher total hospital charges ($207,253 compared with $66,823). A
      number of comorbidities and procedure-related factors were identified as
      independent risk factors for VTE. CONCLUSIONS: We present a VTE Risk Index, based
      on the independent risk factors identified in this study, for the VTE following
      spinal fusion. In conjunction with current guidelines, this risk index can be
      used to guide clinical decision-making regarding VTE prophylaxis in patients
      undergoing spinal fusion. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24897743
TI  - Lack of Benefit of Physical Therapy on Function Following Supracondylar Humeral
      Fracture: A Randomized Controlled Trial.
AB  - BACKGROUND: The goal of the study was to evaluate the efficacy of physical
      therapy in restoring function and mobility after a pediatric supracondylar
      humeral fracture. METHODS: The study included sixty-one patients from five to
      twelve years of age with a supracondylar humeral fracture that was treated with
      casting or with closed reduction and pinning followed by casting. Patients were
      randomized to receive either no further treatment (no-PT group) or six sessions
      of a standardized hospital-based physical therapy program (PT group). The ASK-p
      (Activities Scale for Kids-performance version) and self-assessments of activity
      were used to assess function at one, nine, fifteen, and twenty-seven weeks after
      injury. Motion was measured at nine and fifteen weeks after injury by a blinded
      therapist. Anxiety was measured at one and nine weeks after injury with a self
      assessment. Differences in ASK-p scores and anxiety level were analyzed with use
      of multivariate generalized estimating equations. RESULTS: ASK-p scores were
      significantly better in the no-PT group at nine and fifteen weeks after injury (p
      = 0.02 and 0.01, respectively) but the difference at twenty-seven weeks was not
      significant. There were no differences between groups with respect to performance
      of activities of daily living or time to return to sports. Anxiety at nine weeks
      was associated with worse ASK-p scores at nine and fifteen weeks in the PT group
      and with better ASK-p scores in the no-PT group at these time points (p = 0.01
      and 0.02, respectively). There were no differences between the groups with
      respect to elbow motion in the injured arm at any time. Severity of injury had no
      impact on function or elbow motion in either the PT or the no-PT group.
      CONCLUSIONS: Children undergoing closed treatment of a supracondylar humeral
      fracture that was limited to approximately three weeks of cast immobilization
      received no benefit involving either return of function or elbow motion from a
      short course of physical therapy. LEVEL OF EVIDENCE: Therapeutic Level I. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24897744
TI  - Does CT Angiography Matter for Patients with Cervical Spine Injuries?
AB  - BACKGROUND: Cervical injury can be associated with vertebral artery injury. This
      study was performed to determine the impact of computed tomography (CT)
      angiography of the head and neck on planning treatment of cervical spine
      fracture, if these tests were ordered appropriately, and to estimate cost and
      associated exposure to radiation and contrast medium. METHODS: This retrospective
      review included all patients who underwent CT of the cervical spine and CT
      angiography of the head and neck from January 2010 to August 2011 at one
      institution. Patients were divided into those with and those without cervical
      spine fracture seen on CT of the cervical spine. We determined if the CT
      angiography of the head and neck was positive for vascular injury in the patients
      with a cervical fracture. Vascular injury treatment and alterations in surgical
      fracture treatment due to positive CT angiography of the head and neck were
      recorded. A scan was deemed appropriate if it had been ordered per established
      institutional protocol. RESULTS: Of the 381 patients who underwent CT angiography
      of the head and neck, 126 had a cervical injury. Sixteen of the CT angiography
      studies were appropriately ordered for non-spinal indications, and twenty-three
      were inappropriately ordered. The CT angiography was positive for one patient for
      whom the imaging was off protocol and one for whom the indication was non-spinal.
      Nineteen patients had positive CT angiography of the head and neck; no patient
      underwent surgical intervention for a vascular lesion. Eleven patients underwent
      surgical intervention for a cervical fracture; the operative plan was changed
      because of vascular injury in one case. The CT angiography was positive for
      eleven of forty-eight patients who had sustained a C2 fracture; this group
      accounted for eleven of the nineteen positive CT angiography studies.
      Noncontiguous injuries occurred in nineteen patients; three had positive CT
      angiography of the head and neck. The approximate charge for the CT angiography
      was $3925, radiation exposure was approximately 4000 mGy/cm, and contrast-medium
      load was approximately 100 mL. CONCLUSIONS: Positive CT angiography of the head
      and neck rarely altered surgical treatment of cervical spine injuries. This study
      supports the findings in the literature that C1-C3 spine injuries have an
      increased association with vertebral artery injury. CT angiography of the head
      and neck ordered off protocol had a low likelihood of being positive. Strict
      adherence to protocols for CT angiography of the head and neck can reduce costs
      and decrease unnecessary exposure to radiation and contrast medium. LEVEL OF
      EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24897745
TI  - Diagnosis and Management of Periprosthetic Shoulder Infections.
AB  - ? The unique bacterial flora of the shoulder present diagnostic and treatment
      challenges that are distinct from those seen with failed hip and knee
      arthroplasties.? The presentation, diagnosis, and management of suppurative
      periprosthetic joint infections of the shoulder are similar to those of the hip
      and the knee.? Failed arthroplasties with positive cultures (FAPCs) are poorly
      performing shoulder reconstructions associated with low-virulence microorganisms
      that do not evoke a suppurative inflammatory response. Propionibacterium acnes is
      the predominant bacterium isolated from these cases.? With improved surgeon
      awareness and the addition of longer tissue-culture incubation times, detection
      of FAPCs has become more common. However, management is hampered by the lack of
      reliable, timely tests that can determine the presence of less virulent organisms
      in the preoperative or intraoperative settings.? The implications of positive
      culture results in FAPCs are unclear. Key test characteristics such as the false
      positive rate and the prevalence of positive cultures in well-performing
      shoulders are unknown as there is no useful confirmatory test to validate the
      culture data and no reliable way to detect the presence of less virulent
      microorganisms without reoperation.? Soft-tissue and osseous deficits are
      frequently encountered when revising previously infected shoulders. The rate of
      complications in these scenarios is high, and the outcomes are the least
      favorable compared with revisions for any other indication.? The development of a
      consensus definition of a periprosthetic shoulder infection is critical to future
      investigations of these devastating complications.

PMID- 24897746
TI  - Preoperative Opioid Use as a Predictor of Adverse Postoperative Self-Reported
      Outcomes in Patients Undergoing Spine Surgery.
AB  - BACKGROUND: Opioids are commonly used for preoperative pain management in
      patients undergoing spine surgery. The objective of this investigation was to
      assess whether preoperative opioid use predicts worse self-reported outcomes in
      patients undergoing spine surgery. METHODS: Five hundred and eighty-three
      patients undergoing lumbar, thoracolumbar, or cervical spine surgery to treat a
      structural lesion were included in this prospective cohort study. Self-reported
      preoperative opioid consumption data were obtained at the preoperative visit and
      were converted to the corresponding daily morphine equivalent amount. Patient
      reported outcome measures were assessed at three and twelve months
      postoperatively via the 12-Item Short-Form Health Survey and the EuroQol-5D
      questionnaire, as well as, when appropriate, the Oswestry Disability Index and
      the Neck Disability Index. Separate multivariable linear regression analyses were
      then performed. RESULTS: At the preoperative evaluation, of the 583 patients, 56%
      (326 patients) reported some degree of opioid use. Multivariable analyses
      controlling for age, sex, diabetes, smoking, surgery invasiveness, revision
      surgery, preoperative Modified Somatic Perception Questionnaire score,
      preoperative Zung Depression Scale score, and baseline outcome score found that
      increased preoperative opioid use was a significant predictor (p < 0.05) of
      decreased 12-Item Short-Form Health Survey and EuroQol-5D scores, as well as of
      increased Oswestry Disability Index and Neck Disability Index scores at three and
      twelve months postoperatively. Every 10-mg increase in daily morphine equivalent
      amount taken preoperatively was associated with a 0.03 decrease in the 12-Item
      Short-Form Health Survey physical component summary and mental component summary
      scores, a 0.01 decrease in the EuroQol-5D score, and a 0.5 increase in the
      Oswestry Disability Index and Neck Disability Index score at twelve months
      postoperatively. Higher preoperative Modified Somatic Perception Questionnaire
      and Zung Depression Scale scores were also significant negative predictors (p <
      0.05). CONCLUSIONS: Increased preoperative opioid consumption, Modified Somatic
      Perception Questionnaire score, and Zung Depression Scale score prior to
      undergoing spine surgery predicted worse patient-reported outcomes. This suggests
      the potential benefit of psychological and opioid screening with a
      multidisciplinary approach that includes weaning of opioid use in the
      preoperative period and close opioid monitoring postoperatively. LEVEL OF
      EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24897747
TI  - Assessing the Effects of Teriparatide Treatment on Bone Mineral Density, Bone
      Microarchitecture, and Bone Strength.
AB  - BACKGROUND: To gain insight into how teriparatide affects various bone health
      parameters, we assessed the effects of teriparatide treatment with use of
      standard DXA (dual x-ray absorptiometry) technology and two newer technologies,
      high-resolution MRI (magnetic resonance imaging) and finite element analysis of
      quantitative CT (computed tomography) scans. METHODS: In this phase-4, open-label
      study, postmenopausal women with severe osteoporosis received 20 MUg/day of
      teriparatide. Assessments included (1) changes in areal BMD (bone mineral
      density) (in g/cm2) at the radius, spine, and hip on DXA, (2) changes in
      volumetric BMD (in mg/cm3) at the spine and hip on quantitative CT scans, (3)
      changes in bone microarchitecture at the radius on high-resolution MRI, (4)
      estimated changes in spine and hip strength according to finite element analysis
      of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6)
      safety. RESULTS: Thirty-five subjects were enrolled; thirty completed eighteen
      months and twenty-five completed an optional six-month extension. No significant
      changes were observed for the primary outcome, high-resolution MRI at the distal
      aspect of the radius. At month eighteen, the least-squares mean percentage change
      from baseline in total volumetric BMD at the spine was 10.05% (95% confidence
      interval [CI], 6.83% to 13.26%; p < 0.001), and estimated spine strength
      increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at
      the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip
      strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased
      at the lumbar spine and femoral neck, was unchanged for the total hip and at the
      distalmost aspect of the radius, and decreased at a point one-third of the
      distance between the wrist and elbow. Bone turnover markers increased at months
      three, six, and twenty-four (all p < 0.05). No unexpected adverse events were
      observed. CONCLUSIONS: High-resolution MRI failed to identify changes in bone
      microarchitecture at the distal aspect of the radius, a non-weight-bearing site
      that may not be suitable for assessing effects of an osteoanabolic agent.
      Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD
      at the spine and hip. Estimated vertebral and femoral strength also increased.
      These findings and increases in bone turnover markers through month twenty-four
      are consistent with the known osteoanabolic effect of teriparatide. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24897748
TI  - Primary Arthrodesis of the Tibiotalar Joint in Severely Comminuted High-Energy
      Pilon Fractures.
AB  - BACKGROUND: The treatment of highly comminuted tibial pilon fractures is
      controversial. The aim of this study was to determine the effectiveness and
      outcomes of primary arthrodesis following highly comminuted tibial plafond
      fractures. METHODS: A database search was performed to identify all patients who
      underwent blade plate arthrodesis at our institution over a sixteen-year period.
      Inclusion criteria included patients with an Arbeitsgemeinschaft fur
      Osteosynthesefragen/Orthopaedic Trauma Association type-C2 or type-C3 pilon
      fracture that was deemed to be non-reconstructable by the treating surgeon.
      Outcomes were measured using the Short-Form 36-Item Health Survey, time to
      independent walking, time to consolidation of the arthrodesis, and wound-healing
      complications. RESULTS: A total of twenty patients were included in this study,
      and seventeen patients (85%) were available for follow-up at a minimum of two
      years after their surgery. Wound infections or wound dehiscence did not occur in
      this series. All patients were walking without crutches or a walker at their
      latest follow-up. One patient developed an aseptic nonunion and healed
      successfully after revision surgery. CONCLUSIONS: Blade plate ankle fusion using
      a posterior approach is a reliable method for the treatment of a small subset of
      patients with severely comminuted, non-reconstructable pilon fractures. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24897749
TI  - Prevalence, Distribution, and Surgical Relevance of Abnormal Pedicles in Spines
      with Adolescent Idiopathic Scoliosis vs. No Deformity: A CT-Based Study.
AB  - BACKGROUND: A thorough understanding of pedicle morphology is necessary for
      pedicle screw placement. Previous studies classifying pedicle morphology, to our
      knowledge, have neither discussed the range of abnormal morphology nor correlated
      patient or curve characteristics with abnormal morphology to identify at-risk
      pedicles. METHODS: With the use of computed tomography (CT) images, we analyzed a
      total of 6116 pedicles from ninety-five patients without spinal deformity (forty
      two females and fifty-three males) and ninety-one patients with adolescent
      idiopathic scoliosis (AIS) (sixty-eight females and twenty-three males). Pedicle
      morphology was classified as: Type A, a cancellous channel of >4 mm; Type B, a
      cancellous channel of 2 to 4 mm; Type C, a cortical channel of >=2 mm; or Type D,
      a cortical or cancellous channel of <2 mm. Types B, C, and D were defined as
      abnormal. Patient demographic data and pedicle distribution were assessed for
      prevalence and likelihood of abnormal pedicle morphology. Postoperative CT images
      from fifty-nine patients with AIS were used to assess screw placement. RESULTS:
      There was a significantly higher rate of abnormal pedicles in patients with AIS
      (p = 0.001). More abnormal pedicles were located in the thoracic spine compared
      with the lumbar spine both in patients without deformity (13.3% versus 2.0%) and
      patients with AIS (31.9% versus 2.4%). Significantly more abnormal pedicles were
      located on the concavity (p < 0.001), within the periapical region (p = 0.02),
      and on the apex of the curve (p = 0.03). Three times as many pedicle screws were
      misplaced in abnormal pedicles compared with normal pedicles (21% versus 7%).
      CONCLUSIONS: Our study found a significantly higher prevalence of abnormal
      pedicles in the patients with AIS. Of the abnormal pedicles in these patients,
      most were in the thoracic spine, on the concave side, and in the periapical and
      apical regions. CLINICAL RELEVANCE: Knowledge of abnormal pedicles may enable
      surgeons to anticipate and plan for difficult screw placement and further
      decrease risk to the patient.

PMID- 24897750
TI  - Key Issues and Opportunities in the Evolving Health-Care Marketplace: AOA
      Critical Issues.

PMID- 24897751
TI  - ACGME Accreditation of Orthopaedic Surgery Subspecialty Fellowship Training
      Programs.
AB  - BACKGROUND: Orthopaedic surgery training in the United States consists of a five
      year-minimum orthopaedic surgery residency program, followed by optional
      subspecialty fellowship training. There is an increasing trend for trainees to
      complete at least one fellowship program following residency training, with
      approximately 90% of current trainees planning to complete a fellowship. The
      purpose of this investigation was to assess the overall variability of
      orthopaedic subspecialty fellowships in terms of characteristics, match process,
      and the tendency to be accredited by the Accreditation Council for Graduate
      Medical Education. METHODS: Nine orthopaedic surgery subspecialties were assessed
      for their fellowship match program, their number of fellowship programs and
      positions in the match, and the number of programs and positions accredited by
      the Accreditation Council for Graduate Medical Education. Programs with a
      Subspecialty Certificate offered by the American Board of Orthopaedic Surgery
      were compared with programs without a Subspecialty Certificate. Comparative
      statistics utilizing an unpaired t test with a statistical cutoff of p < 0.05
      were performed. RESULTS: Three separate matching programs are used by the nine
      subspecialties. Hand surgery utilizes the National Residents Matching Program,
      shoulder and elbow surgery utilizes the American Shoulder and Elbow Surgeons
      Fellowship Match, and the other seven subspecialties utilize the San Francisco
      Matching Program. In total, 478 fellowship programs were identified, representing
      897 fellowship positions. The highest percentage of fellowship programs that are
      accredited by the Accreditation Council for Graduate Medical Education was in
      orthopaedic sports medicine (93.1%), compared with the lowest percentage in foot
      and ankle orthopaedics (16.3%). A significantly higher percentage (p < 0.05) of
      fellowship programs accredited by the Accreditation Council for Graduate Medical
      Education were found for subspecialties with American Board of Orthopaedic
      Surgery Subspecialty Certificates (hand and sports) (87.9%) compared with
      subspecialties without Subspecialty Certificates (34.3%). CONCLUSIONS: There are
      more orthopaedic subspecialty fellowship positions available annually than there
      are graduating orthopaedic surgery residents. Three independent matching programs
      are currently being used by the nine orthopaedic subspecialties. Subspecialties
      vary in the proportion of programs with Accreditation Council for Graduate
      Medical Education accreditation. Subspecialties with American Board of
      Orthopaedic Surgery Subspecialty Certificates have a significantly greater
      proportion of fellowship programs accredited by the Accreditation Council for
      Graduate Medical Education compared with those without Subspecialty Certificates.
      CLINICAL RELEVANCE: Orthopaedic subspecialty fellowship programs are rapidly
      becoming a perceived necessity as part of orthopaedic surgery training.
      Fellowships continue to vary in matching system and their accreditation
      characteristics.

PMID- 24897752
TI  - MRSA Clone Wars: Defeating the Epidemic: Commentary on an article by Inge Skramm,
      MD, PhD, et al.: "Surgical Site Infections in Orthopaedic Surgery Demonstrate
      Clones Similar to Those in Orthopaedic Staphylococcus aureus Nasal Carriers".

PMID- 24897753
TI  - Just Because We Can Cut, Should We? Commentary on an article by Daniel A. Osei,
      MD, et al.: "Simultaneous Bilateral or Unilateral Carpal Tunnel Release? A
      Prospective Cohort Study of Early Outcomes and Limitations".

PMID- 24897754
TI  - Early Surgical Decompression: Too Early or Too Late? Commentary on an article by
      James Jung, BS, et al.: "Early Surgical Decompression Restores Neurovascular
      Blood Flow and Ischemic Parameters in an in Vivo Animal Model of Nerve
      Compression Injury".

PMID- 24897755
TI  - Metabolic power demands of rugby league match play.
AB  - PURPOSE: To describe the metabolic demands of rugby league match play for
      positional groups and compare match distances obtained from high-speed-running
      classifications with those derived from high metabolic power. METHODS: Global
      positioning system (GPS) data were collected from 25 players from a team
      competing in the National Rugby League competition over 39 matches. Players were
      classified into positional groups (adjustables, outside backs, hit-up forwards,
      and wide-running forwards). The GPS devices provided instantaneous raw velocity
      data at 5 Hz, which were exported to a customized spreadsheet. The spreadsheet
      provided calculations for speed-based distances (eg, total distance; high-speed
      running, >14.4 km/h; and very-high-speed running, >18.1 km/h) and metabolic-power
      variables (eg, energy expenditure; average metabolic power; and high-power
      distance, >20 W/kg). RESULTS: The data show that speed-based distances and
      metabolic power varied between positional groups, although this was largely
      related to differences in time spent on field. The distance covered at high
      running speed was lower than that obtained from high-power thresholds for all
      positional groups; however, the difference between the 2 methods was greatest for
      hit-up forwards and adjustables. CONCLUSIONS: Positional differences existed for
      all metabolic parameters, although these are at least partially related to time
      spent on the field. Higher-speed running may underestimate the demands of match
      play when compared with high-power distance-although the degree of difference
      between the measures varied by position. The analysis of metabolic power may
      complement traditional speed-based classifications and improve our understanding
      of the demands of rugby league match play.

PMID- 24897756
TI  - Authors' reply.

PMID- 24897757
TI  - Authors' reply.

PMID- 24897758
TI  - [A consultation day for physicians in clinics and hospitals].

PMID- 24897759
TI  - Evidence-based review and discussion points.

PMID- 24897760
TI  - Retromolar mass. Mucoepidermoid carcinoma.

PMID- 24897761
TI  - Medicine: the science and art of compassionate care.

PMID- 24897762
TI  - Physicians and new care models.

PMID- 24897763
TI  - Physician burnout: health care systems seek wellness solutions.

PMID- 24897764
TI  - Engaging physician leaders for improved outcomes.

PMID- 24897766
TI  - Integrating mission into physician practices.

PMID- 24897765
TI  - The role of the hospitalist.

PMID- 24897767
TI  - Correctional health care: a forgotten ministry of the church.

PMID- 24897768
TI  - Matrix connects Catholic principles to patient experience.

PMID- 24897769
TI  - Preparing medical students for an ever-changing world.

PMID- 24897770
TI  - Early pregnancy complications and the Ethical and Religious Directives.

PMID- 24897771
TI  - A hospital rises in Haiti.

PMID- 24897772
TI  - More than old wine in new wineskins: reform means transformation.

PMID- 24897773
TI  - Inflammatory myofibroblastic tumour: a rare entity with wide differential
      diagnosis.
AB  - Inflammatory myofibroblastic tumour (IMT) is a rare, distinctive mesenchymal
      neoplasm. Grossly, it appears as a circumscribed mass with a rubbery to firm cut
      surface. Microscopically, it is characterized by a spindle cell proliferation
      within a myxoid stroma with admixed plasma cells, lymphocytes and eosinophils.
      Immunohistochemical staining is usually positive for vimentin, smooth muscle
      actin (SMA) and anaplastic lymphoma kinase (ALK). ALK gene rearrangement is
      present in approximately 50-70% IMTs. The standard treatment is surgical
      resection, and it is essential to differentiate IMT from benign and malignant
      mimickers so that appropriate therapy may be provided. Clinical and radiological
      follow-up is required to detect recurrence.

PMID- 24897774
TI  - Combined hepato-cholangiocarcinoma arising in a gallbladder intracystic papillary
      neoplasm. A new view on so-called "hepatoid adenocarcinoma of the gallbladder".
AB  - A 62-year-old female presented with abdominal pain, weight loss of 20 kg in the
      prior 6 months, and a palpable mass in the right upper quadrant during physical
      exam. Standard liver tests, including screening for hepatitis B and C and alpha
      fetoprotein were negative or within normal limits. Computerized tomography
      depicted a transmural gallbladder tumor infiltrating into the adjacent liver with
      an irregular ill-defined mass occupying segments IV-V-VI, measuring 13.0 x 9.2 x
      8.5 cm, with a solid-cystic component and heterogeneous captation of endovenous
      contrast media. Complete surgical resection of the neoplasm was achieved through
      an extended cholecystectomy and excision of hepatic segments IV, V and VI, with
      an uneventful follow-up 29 months until now. Morphological and
      immunohistochemical assessment favored a diagnosis of combined hepatocellular
      cholangiocarcinoma arising in a gallbladder intracystic papillary neoplasm with
      invasive carcinoma. This case raises the hypothesis that the so-called "hepatoid
      adenocarcinoma of the gallbladder" may presently be better understood as a
      neoplasm derived from hepatobiliary stem/progenitor cells. Such cells have been
      recognized in the canals of Hering, in peribiliary glands within the liver and in
      the extrahepatic biliary tree, and in gallbladder mucosa.

PMID- 24897775
TI  - A rare case of transmural endometriosis in primary adenocarcinoma of the rectum.
AB  - Intestinal endometriosis of the rectum and sigmoid colon, occurring in up to 34%
      of pelvic endometriosis, mimics a wide number of conditions that are difficult to
      differentiate from inflammatory or malignant diseases. Herein we report the first
      case of transmural endometriosis concomitant with advanced primary rectal
      adenocarcinoma, presenting with obstructive symptoms. Correct diagnosis based on
      morphological identification and immunohistochemical characterization of the two
      entities is crucial for treatment.

PMID- 24897776
TI  - Collision tumour of the breast composed of Merkel cell carcinoma and invasive
      ductal carcinoma: a case report.
AB  - We report a case of a 71-year-old female with a palpable breast mass. Pathologic
      evaluation of the breast mass showed a unique collision tumour with a high-grade
      invasive and in-situ ductal carcinoma component and a high-grade neuroendocrine
      carcinoma component. The neuroendocrine component turned out to be Merkel cell
      carcinoma (MCC), with immunohistochemical confirmation. To the best of our
      knowledge, this is the first case report of a collision tumour with ordinary
      ductal carcinoma and MCC in the breast.

PMID- 24897777
TI  - Intestinal tuberculosis: a diagnostically-challenging case misdiagnosed as
      Crohn's disease at colorectal biopsy.
AB  - The clinical presentation of two different digestive diseases such as Crohn's
      disease and intestinal tuberculosis may be so similar to induce a delay in
      correct diagnosis and appropriate treatment (immune suppression versus antibiotic
      therapy). Herein, we describe the case of a young man from Eastern Europe who
      came to our observation complaining of clinical symptoms initially misdiagnosed
      as an inflammatory bowel disease. It is important to keep in mind the possibility
      of an active tubercular disease, particularly in patients coming from countries
      endemic for the disease. Morphological findings of sarcoid-like granulomas at
      biopsy is not enough for a conclusive diagnosis of Crohn's disease, and
      tuberculosis should be ruled out on the basis of clinical information, laboratory
      tests and radiological imaging.

PMID- 24897778
TI  - Primary tumour of the round ligament of the liver: a case presentation.
AB  - A 40-year-old Caucasian female patient presented to the outpatient General
      Surgery ward in "V. I. Lenin" Teaching Hospital complaining of a recurrent
      mesogastric pain that had lasted for 3 months. Physical examination showed a
      palpable mass confined to that area. She was then admitted with diagnosis of an
      abdominal tumour. Diagnostic work-up revealed that the process involved the round
      ligament of the liver, which is an exceptional localization, which motivated us
      to publish this case after surgical treatment by excision, having also taken into
      account the results of histopathology which revealed a PEComa, confirmed by
      inmunohistochemistry. After reviewing the available literature, the low incidence
      of these lesions, as well as the unusual histological variety, makes the present
      case one of interest.

PMID- 24897779
TI  - Metastasizing pleomorphic adenoma of the submandibular gland: a case report.
AB  - Pleomorphic adenoma (PA), originally called mixed tumour, is the most common
      neoplasm of the salivary glands. It is usually a benign, slow-growing and well
      circumscribed tumour. However, PA may occasionally give rise to metastases that
      usually occur after a previous recurrence. These tumours display benign
      histological features in both primary tumours and metastases. Such tumours have
      been termed metastatic PA or metastatic mixed tumours. We report a case of
      metastatic PA of the submandibular gland with metastasis to the cervical lymph
      nodes.

PMID- 24897780
TI  - Fibroadenoma in an ectopic vulvar breast gland: a common neoplasm in an uncommon
      site.
AB  - Ectopic breast tissue is defined as glands located outside of the breast. It can
      be found anywhere along the milk line extending from the axilla to the groin, and
      can occur in the vulva. Ectopic breast tissue should be excised because it may
      develop benign or malignant pathologic processes. Less than 40 cases of
      fibroadenoma in the vulva have been reported in the literature. We report a case
      of a 37-year-old woman presenting a solitary vulvar mass. The mass was excised
      completely, and histology demonstrated an ectopic breast fibroadenoma. This is
      one of the few reports on the benign pathologies of vulvar mammary glands.

PMID- 24897781
TI  - New guidelines for geriatric EDs: guidance focused on boosting environment, care
      processes.
AB  - A cadre of prominent medical groups, including the ACEP, ENA, AGS, and SAEM, has
      unveiled a comprehensive set of Geriatric Emergency Department Guidelines to aid
      hospitals that are either in the process of opening senior-focused EDs or
      revamping their policies and procedures to better meet the needs of an aging
      population. The guidelines offer recommendations related to staffing,
      infrastructure, education, and transition-of-care strategies. In addition, they
      outline a host of screenings that studies have shown are beneficial for older
      adults. Experts note that hospital systems around the country have already opened
      50 geriatric EDs, with many more facilities in development. Guideline authors
      state that the guidelines take an evidence-based approach to managing senior
      patients. While more cost and outcomes data are needed, experts say that senior
      focused improvements to emergency care can reduce admissions and return visits to
      the ED while also boosting patient satisfaction. Future efforts will focus on
      prioritizing the guideline recommendations so that ED administrators concerned
      with improving senior care will tackle the most important changes first.

PMID- 24897782
TI  - Care transitions: geriatric medicine offers a roadmap to follow.

PMID- 24897783
TI  - Emergency providers see big potential for Google Glass.
AB  - Emergency providers are among the first in health care to experiment with Google
      Glass, a computer that is worn like a traditional set of glasses, enabling
      clinicians to pull up critical information from a patient's electronic medical
      record (EMR) or call for assistance without looking away from the patient.
      Special applications of the device can also be used to facilitate telemedicine
      consults with specialists while patients are still in the ED. According to early
      users, protecting patient privacy has not been a problem in early applications of
      the device. However, state-level laws remain a barrier to large-scale
      implementation of the technology in some regions. Emergency providers at Beth
      Israel Deaconess Medical Center in Boston, MA, see Google Glass as another
      platform for their ED information system. The approach is being used to
      facilitate hands-free communications and to expedite workflow. At Rhode Island
      Hospital in Providence, RI, emergency providers are testing a telemedicine
      application for Glass that enables providers to connect patients with off-site
      dermatologists while they are still in the ED, eliminating the need for
      additional specialty appointments. Early users believe that Glass and similar
      innovations will eventually play a strong role in preventing readmissions by
      providing remote care to patients--especially in the first few days following
      discharge from the hospital or ED.

PMID- 24897785
TI  - Wonder world of phages: potential biocontrol agents safeguarding biosphere and
      health of animals and humans- current scenario and perspectives.
AB  - Darwin's theory of natural selection and concept of survival of fittest of
      Wallace is a universal truth which derives the force of life among all live
      entities on this biosphere. Issues regarding food safety along with increased
      drug resistance and emerging zoonotic infections have proved that
      multidisciplinary efforts are in demand for human and animal welfare. This has
      led to development of various novel therapies the list of which remains
      incomplete without mentioning about phages. Homologous and non-homologous
      recombination along with point mutation and addition of new genes play role in
      their evolution. The rapid emergence of the antibiotic resistant strains of
      bacteria have created keen interest in finding necessary alternatives to check
      microbial infections and there comes the importance of phages. Phages kill the
      bacteria either by lysis or by releasing holins. Bacteriophages; the viruses that
      live on bacteria are nowadays considered as the best biocontrol agents. They are
      used as replacers of antibiotics; food industry promoter; guard of aquatic life
      as well as of plants; pre-slaughter treatment agents; Generally Recognized As
      Safe (GRAS) food additives; Typing agent of bacteria; active tool of super bug
      therapy; in post harvest crops and food and during post infection and also to
      combat intracellular pathogens viz. Mycobacteria and Mycoplasma.
      Cyanophages/phycophages are particularly useful in controlling blooms produced by
      various genera of algae and cyanobacteria. By performing centrifugation studies
      and based on electron microscopy certain virus like particles containing ds RNA
      have been confirmed as mycophages. They are well proven as threat to pathogenic
      fungi (both fungal hyphae and yeast). Those that infect yeasts are called
      zymophages. Virophages have exquisite specificity for their viral host, hence can
      extensively be used for genetic studies and can also act as evolutionary link.
      After the discovery of very first virophage till now, a total of 3 virophages
      have been discovered including the Sputnik virophages that are used to study
      genetic recombination. Virophages also find their application in antiviral
      therapy; as engineer of ecological system etc. In brief, present review deals
      with various dimensions of these beneficial viruses that are being used and can
      be successfully used in future for safeguarding biosphere including animal and
      human health.

PMID- 24897784
TI  - Bacteriophage therapy for safeguarding animal and human health: a review.
AB  - Since the discovery of bacteriophages at the beginning of the 19th century their
      contribution to bacterial evolution and ecology and use in a variety of
      applications in biotechnology and medicine has been recognized and understood.
      Bacteriophages are natural bacterial killers, proven as best biocontrol agents
      due to their ability to lyse host bacterial cells specifically thereby helping in
      disease prevention and control. The requirement of such therapeutic approach is
      straight away required in view of the global emergence of Multidrug Resistant
      (MDR) strains of bacteria and rapidly developing resistance to antibiotics in
      both animals and humans along with increasing food safety concerns including of
      residual antibiotic toxicities. Phage typing is a popular tool to differentiate
      bacterial isolates and to identify and characterize outbreak-associated strains
      of Salmonella, Campylobacter, Escherichia and Listeria. Numerous methods viz.
      plaque morphology, ultracentrifugation in the density gradient of CsCl2, and
      random amplified polymorphic DNA (RAPD) have been found to be effective in
      detection of various phages. Bacteriophages have been isolated and recovered from
      samples of animal waste products of different livestock farms. High titer
      cocktails of broad spectrum lytic bacteriophages are usually used for clinical
      trial for assessing their therapeutic efficacy against antibiotic unresponsive
      infections in different animals. Bacteriophage therapy also helps to fight
      various bacterial infections of poultry viz. colibacillosis, salmonellosis and
      listeriosis. Moreover, the utility of phages concerning biosafety has raised the
      importance to explore and popularize the therapeutic dimension of this promising
      novel therapy which forms the topic of discussion of the present review.

PMID- 24897786
TI  - Nutrigenomics and its role in male puberty of cattle: a mini review.
AB  - Nutrigenomics a novel era in genomics research is based on puzzling issue on how
      nutrition and genes re-interacts. Perusal of literature reveals that very few
      information are available in this field and especially when it is associated with
      puberty in cattle which is a multigenic trait of great economic importance. Thus
      it opens a new area of research interest. Various markers like-gonadotropin
      releasing hormone/GNRH (responsible for sexual differentiation and reproduction),
      interstitial growth regulating factor/IGF1 (having signal controlling
      reproduction function linked to somatic growth); circulating metabolic hormones
      viz., leptin apart from GnRH and IGF1 (having impact on testicular development in
      peripubertal bull) are proved to be associated with male puberty in cattle.
      Various minerals (copper, selenium, manganese, zinc, chromium, iron and
      molybdenum) and vitamins (Vit. A, D, E and C) are directly or indirectly linked
      to male puberty. But no research till today initiated how the nutrients effect on
      the transcriptome/proteome/metabolome level of marker genes associated with male
      puberty in cattle. Application of nanotechnology to make food safer for promotion
      of good health has created much excitement and nanoparticles has been developed
      against infectious diseases (e.g., Campylobacteriosis) affecting puberty along
      with certain nanocarriers that can facilitate the uptake of essential nutrients
      associated with puberty. Much of nutrigenomics research is however in infancy and
      hence the present mini-review will allow building the concept among researchers
      and scientists to initiate research in this interesting area.

PMID- 24897787
TI  - Support vector machines for microscopic medical images compression.
AB  - This study presents the compression of microscopic medical images by Support
      Vector Machines using machine learning. The visual cortex is the largest system
      in the human brain and is responsible for image processing such as compression,
      because the eye does not necessarily perceive all the details of an image.
      Medical images are a valuable means of decision support. However, they provide a
      large number of images per examination that can be transmitted over a network or
      stored for several years under the law imposed by the country. To apply the
      reasoning of biological intelligence, this study uses Support Vector Machines for
      compression to reduce the pixels of medical images in order to transmit data in
      less time and store information in less space. The results found by using this
      method are satisfactory for compression though the time must be improved.

PMID- 24897788
TI  - Evaluation of antihyperlipidemic potency of a polyherbomineral formulation (AF
      LIP) in experimental animal models.
AB  - There is a growing interest in the screening of antihyperlipidemic activity and
      the present study deals with the screening of a polyherbomineral formulation (AF
      LIP) which possess many important ingredients reported to have antihyperlipidemic
      potency. Acute antihyperlipidemic activity was evaluated by using Triton WR-1339
      (100 mg kg(-1)) and chronic, induced by high fat diet. Total Cholesterol (TC),
      triglycerides (TG), Low Density Lipoproteins (LDL), High Density Lipoproteins
      (HDL) and Very Low Density Lipoproteins (VLDL) were examined in addition to HMG
      CoA reductase enzyme activity and fecal cholesterol excretion. In Triton WR-1339
      (acute model) at the dose of 400 mg kg(-1), AF-LIP significantly lowered TC, TG,
      very Low Density Lipoproteins Cholesterol (VLDL-C), Low Density Lipoproteins
      Cholesterol (LDL-C) levels with simultaneous increase in High Density
      Lipoproteins Cholesterol (HDL-C) levels (p < 0.01) at 6 and 24 h. Also there was
      significant reduction in TC and LDL-C levels at 48 h at the dose of 400 mg kg(
      1). In chronic model also at the dose of 100, 200 and 400 mg kg(-1), AF-LIP
      significantly reduced (p < 0.001) TC and LDL-C levels with increase in HDL-C
      levels. TG and VLDL-C levels were also not much affected. HMG-CoA reductase
      enzyme activity when estimated was not much decreased. Also AF-LIP showed
      significant reduction in atherogenic index (p < 0.01) with significant increase
      in HDL/TC ratio (p < 0.01). Fecal cholesterol excretion was significantly
      enhanced (p < 0.01) in all the test doses of AF-LIP. AF-LIP may be beneficial for
      the treatment of atherosclerosis, since atherosclerosis is one of the secondary
      complications of hyperlipidemia.

PMID- 24897790
TI  - Dieback and sooty canker of Ficus trees in Egypt and its control.
AB  - This study was designed to throw lights on dieback and canker disease on urban
      trees of Ficus sp. in Egypt, its causal pathogens and disease control. Diseased
      samples were collected from five locations. Pathogenicity test was done on one
      year old of three different healthy seedlings of Ficus trees (Ficus benghalensis,
      Ficu snitida and Ficus hawaii). Lasiodiplodia theobromae and Phomopsis sp. were
      consistently isolated from infected tissues and were pathogenic. The fungicides
      Antracol Combi and Topsin M 70 provided effective control of the infection.
      Accordingly, protecting ficus trees from diseases threating is considered a major
      goal to attain their benefits.

PMID- 24897789
TI  - Commercial herbal slimming products: concern for the presence of heavy metals and
      bacteria.
AB  - The increment of rate in obesity, the phenomenon of fat phobia as well as the
      increased use of herbal medicine had lead to the emergence of herbal slimming
      products. However, numerous bacteria and heavy metal contaminations are often
      found in herbal products due to irregular handling practices. Ten different
      brands of products (labeled as A-J) were investigated. Seven heavy metals content
      such as As, Cd, Pb, Co, Cr, Cu and Zn were analyzed using Inductively Coupled
      Plasma-Mass Spectrometry (ICP-MS) and bacterial presence was determined by
      counting the total aerobic count. The identification of isolates was carried out
      by macroscopic and microscopic observation, biochemical tests and confirmation
      using commercial kits of Microgen GN-ID A+B and API 20 E. The heavy metal
      contents in the samples were below the limit of the standard limitation by WHO
      and Health Canada. However, sample A contained the highest total daily intake of
      heavy metals. Total aerobic count was highest in sample H followed by G, A, B, C,
      F, D, E, I and J in which G and H exceeded the standard total aerobic count
      (10(5) CFU g(-1)) as given by WHO. A total of nine isolates of Bacillus spp. and
      ten gram-negative bacteria were isolated in which Bacillus cereus and Pseudomonas
      aeruginosa were found in samples C and F, respectively. Considering the fact that
      the herbal sliming products contained low concentration of heavy metals and
      bacteria count, it should be consumed with caution.

PMID- 24897791
TI  - Phenol content, antioxidant capacity and antibacterial activity of methanolic
      extracts derived from four Jordanian medicinal plants.
AB  - This study was performed to assess the antioxidant and antibacterial properties
      of methanolic extracts derived from aerial parts of four Jordanian medicinal
      plants (Artemisia sieberi, Peganum harmala, Rosmarinus officinalis (Green
      Flowered) and Sarcopterium spinosium). The possible relationship between these
      biological properties and the total phenolic concentrations of these extracts
      were also be determined. The antioxidant capacity and total phenolic
      concentrations were assessed by the ABTS method and Folin-Ciocalteu method,
      respectively. The amount of the extract required to scavenge 50% of ABTS (IC50)
      was also measured. Broth dilution and disc diffusion assays were performed to
      measure the antibacterial activity of these extracts against available bacterial
      strains. Variations were observed among the examined plants in antioxidant and
      antibacterial activities as well as in their phenol contents. According to ABTS
      assay and IC50 value, the highest free radical scavenging potential was found in
      Sarcopterium spinosium, followed by Rosmarinus officinalis, Peganum harmala and
      Artemisia sieberi, respectively. Similarly, the results of antibacterial assays
      showed that Sarcopterium spinosium exhibited the highest antibacterial activity
      against all tested bacterial strains as compared to Rosmarinus officinalis,
      Peganum harmala and Artemisia sieberi. Moreover, Sarcopterium spinosium contained
      the highest amount of phenolic compounds followed by, Rosmarinus officinalis,
      Artemisia sieberi and Peganum harmala, respectively. In conclusion, these plants
      are not only interesting sources for antimicrobial agents but also have a
      considerable amount of antioxidants. In addition, these findings revealed that
      the antioxidant capacity and antibacterial activity of these plant extracts do
      not necessary be attributed to their total phenolic concentrations.

PMID- 24897793
TI  - Pentachlorophenol remediation by Enterobacter sp. SG1 isolated from industrial
      dump site.
AB  - Chlorophenols contamination is serious concern to the environment due toxicity to
      all forms of life. Among all the chlorophenols, pentachlorophenol (PCP) is more
      detrimental to the environment. Pentachlorophenol used as pesticide, herbicide,
      antifungal agent and wood preservative which causes environmental pollution. In
      the present research a PCP degrading bacterium was isolated and characterized
      from industrial dump site. This isolate used PCP as its sole source of carbon and
      energy and was capable of degrading this compound, as indicated by stoichiometric
      release of chloride, ring cleavage activity and biomass formation. Based on
      morphological, biochemical and 16S rRNA gene sequence analysis this strain was
      identified as Enterobacter sp. SG1. Gas Chromatography (GC) analysis revealed
      that this strain was able to degrade PCP up to a concentration of 2 mM. This
      study showed that the removal efficiency of PCP by SG1 was found to be very
      effective and can be used in degradation of PCP contaminated site or waste in the
      environment.

PMID- 24897792
TI  - Antioxidant activity of gilan Mentha pulegium during growth.
AB  - Antioxidant activity and total phenolic contents of methanolic and hydroalcoholic
      acetone extracts of Iranian Mentha pulegium in two stages of maturity were
      investigated. The aim was to investigate the most suitable solvent for extraction
      of antioxidants and to find the correlation existed between plant growth stage
      and its antioxidant capacity. In vitro antioxidant properties of the extracts
      were examined by 1, 1 diphenyl-2-picrylhydrazyl (DPPH) and Ferric
      Reducing/Antioxidant Power (FRAP) methods. Moreover, total phenolic contents were
      determined by the Folin-Ciocalteu method. On the other hand, the phenolic
      compounds were analyzed by chromatographic methods, TLC and SPE-reversed phase
      HPLC. The results revealed that the antioxidant capacities and total phenol
      contents of the extracts in flowering season were higher than pre-flowering
      season. A positive relationship was found between the results obtained from three
      different assay methods used, i.e. FRAP, DPPH and phenol contents. The TLC
      chromatogram of the two extracts showed differences in the number of separated
      compounds of extracts. HPLC results indicated that the fraction collected with
      washing buffer (pH = 6) had highest antioxidant activity.

PMID- 24897794
TI  - Wood specific gravity variation among five important hardwood species of Kashmir
      Himalaya.
AB  - Wood Specific Gravity (SG) is a measure of the amount of structural material a
      tree species allocates to support and strength. In the present study, specific
      gravity varied among the five different woods at three different sites from 0.40
      in Populus nigra at site III (Shopian) to 0.80 in Parrotiopsis jacquemontiana at
      site II (Surasyar). Among the three different sites, specific gravity varied from
      0.73 to 0.80 in Parroptiosis jacquemontiana; in Robinia pseudoacacia it varied
      from 0.71 to 0.79; in Salix alba, it varied from 0.42 to 0.48; In Populus nigra
      it varied from 0.40 to 0.48 and in Juglans regia it varied from 0.59 to 0.66. On
      the basis of the specific gravity variation patterns these woods were categorized
      as light (Salix alba, Populus nigra) moderately heavy (Juglans regia) and
      moderately heavy to heavy (Robinia pseudoacacia, Parrotiopsis jacquemontiana)
      which predicts their properties like strength, dimensional stability with
      moisture content change, ability to retain paint, fiber yield per unit volume,
      suitability for making particleboard and related wood composite materials and
      suitability as a raw material for making paper.

PMID- 24897795
TI  - In vitro antioxidant properties of fucoidan fractions from Sargassum tenerrimum.
AB  - The aim of the present study is conducted to evaluate the antioxidant potential
      and toxicity effect of polysaccharide-fucoidan from the brown seaweed Sargassum
      tenerrimum. Fucoidan-a sulphated polysaccharide contains fucose and sulphate as
      major compounds. Interestingly, various studies reported that the presence of
      sulphate content of the sample plays a significant role in pharmacological
      activities. In this study, fucoidan was fractionated by Ion exchange
      chromatography method and it major chemical constituent sulphate and fucose was
      determined by the biochemical methods. The toxicity effect of fucoidan was
      analyzed by the brine shrimp toxicity assay. Three fucoidan fractions (F1, F2 and
      F3) were obtained from Intact Fucoidan (IF) through anion-exchange column
      chromatography. In vitro antioxidant capability was analyzed by 1, 1-diphenyl-2
      picrylhydrazyl (DPPH), superoxide radical scavenging and total antioxidant assays
      and intact fucoidan showed the maximum activity 83.66 +/- 0.35, 81.73 +/- 0.35%
      and 41.6 +/- 0.43 mg g(-1), respectively. The finding of the present study was
      confirmed that the antioxidant property of fucoidan was depending upon the
      sulphate content of the fraction and these studies proved that fucoidan have non
      toxicity effect. Hence, fucoidan have the scope of being used as natural
      antioxidants in treating many human diseases.

PMID- 24897796
TI  - Flower synchrony, growth and yield enhancement of small type bitter gourd
      (Momordica charantia L.) through plant growth regulators and NPK fertilization.
AB  - Assessment of growth regulator and NPK fertilization effects are important tools
      for flower stimulation and yield improvement in cucurbits. This investigation
      demonstrates the comparative male-female flower induction and fruit yield of
      small sized bitter gourd treated with NPK fertilizers and plant growth
      regulators. Namely, two experiments having three replicates were conducted in a
      Randomized Complete Block Design (RCBD) with NPK fertilization and plant growth
      regulators-GA3, NAA and Ethophon application on small sized bitter gourd-genotype
      BG5 at the research field of the Bangabandhu Sheikh Mujibur Rahman Agricultural
      University (BSMRAU). In experiment 1, different doses of NPK fertilizers
      comprised of 10 treatments and in that of experiment 2, different levels of plant
      growth regulators indicated 10 treatments. The results indicated that application
      of different doses of NPK fertilizer and plant growth regulators significantly (<
      or = 0.05) influenced over the flower initiation and fruit setting. The
      application of N90-P45-K60 fertilizer along with Ethophon spraying resulted in
      the better yield of small sized bitter gourd.

PMID- 24897797
TI  - Antihyperglycaemic activity of the stem-bark extract of Tamarindus indica L. on
      experimentally induced hyperglycaemic and normoglycaemic Wistar rats.
AB  - Diabetes is the most common endocrine disease and its prevalence is reaching
      epidemic proportion worldwide. In 2002, WHO Expert Committee on diabetes mellitus
      recommended an urgent and further evaluation of the folkloric methods of managing
      the disease. In response to this recommendation, several medicinal plants are
      currently being investigated for their hypoglycaemic activity and one of such
      plants is Tamarindus indica. Tamarindus indica is a slow growing tree that is
      resistant to strong winds and perennial. The stem-bark extract of the plant is
      used locally for the management of diabetes. The stem-bark extract of Tamarindus
      indica L. was investigated for its hypoglycemic action on experimentally induced
      hyperglycaemic Wistar rats using a single dose of alloxan monohydrate (150 mg kg(
      1) IP). The oral LD50 of the extract was found to be greater than 5,000 mg kg(
      1). Phytochemical screening revealed the presence of carbohydrates, glycosides,
      saponins, flavonoids, cardiac glycosides, tannins, alkaloids and triterpenes. The
      1000 mg kg(-1) dose of the extract lowered the blood glucose level significantly
      (p < 0.05) at the 4th, 8th and 16th h. The 500 mg kg(-1) lowered the BGL
      significantly (p < 0.05) throughout the study. In the oral glucose load method
      the 1000 mg kg(-1) dose of the extract significantly (p < 0.05) lowered elevated
      blood glucose at the 3rd and 5th. The 500 mg kg(-1) lowered the blood glucose
      from the 1st to the 5th, while the 250 mg kg(-1) also lowered the blood glucose
      level but only significantly at the 5th h. The extract is practically non toxic
      when administered orally. The stem-bark extract of Tamarindus indica Linn
      significantly lowered elevated Blood Glucose concentration (BGL) in the
      experimental animal models, while the crude extract was able to prevent an
      elevation in BGL when used in the oral glucose load model.

PMID- 24897798
TI  - Silicosis and its progress influenced by genetic variation on TNF-alpha locus-
      308, TNF-alpha and IL-10 cytokine on cement factory workers in Indonesia.
AB  - This study aimed to assess the association of Tumor Necrosis Factor (TNF-alpha)
      Locus-308 variant, TNF-alpha and Interleukin (IL-10) Cytokine with the risk of
      silicosis and its progress in Indonesian cement factory workers, There is an
      urgent need to explore the determining factors other than exposure since
      silicosis is chronic progressive and life threatening but remains found, though
      much industrial hygiene effort has been made. This study population was 6,069
      workers registered during 31 December 1990 to 31 December 2003. First,
      prospective study with Nested Case Control design was conducted on 336 workers in
      2003, ten years later the progression of silicosis was assessed in 2013. The
      result showed proportion of the genetic variation on TNF-alpha on Locus -308 in
      Indonesia was significantly (p = 0.02) higher on silicosis (13.45%) than
      nonsilicosis (5.45%) but lower than silicosis in Africa and US miners, since
      susceptibility loci might vary in different ethnic groups. The sign and symptoms
      remained as simple silicosis after ten years; The TNF-alpha:IL-10 ratio > 1 was a
      risk factor in silicosis; the ratio of TNF-alpha:IL-10 > 1 caused a rapid decline
      of lung function compare to ratio < 1, the decline was chronic progressive during
      ten years yet not causing significant dyspnea among the cases. Further studies
      with enlarged sample size are needed. The study concluded, the genetic variation
      on TNF-alpha gene locus -308 was a risk factor of silicosis in Indonesia cement
      factory. Its role is indirect, but through mechanism of controlling the blood
      Cytokine level ratio of TNF-alpha toward IL-10.

PMID- 24897799
TI  - Soaking salted eggs in gambier liquid waste inhibit bacterial growth.
AB  - Gambier liquid waste containing tannin compounds were quite high and serves as an
      antimicrobial agent that will tanning salted eggs so that closed the pores of the
      egg shell and egg to be durable. This study aims to see the effect of soaking
      salted eggs in gambier liquid waste remaining effective in improving the quality
      of salted eggs. This study used a randomized block design with three replicates
      and ten treatments. The treatment were, A: control (no soaking), B: Immersion 49
      h with a gambier liquid waste : distilled water (1:2), C: 25 h (1:2), D: 1 h
      (1:2), E: 49 h (1:1), F:25 h (1:1), G: 1 h (1:1), H: 49 h (1:0), I: 25 h (1:0),
      J: 1 h (1:0). The variables used were water content, bacterial colony forming and
      shelf life. Results of this study showed a significant (p < 0.05) on water
      content, bacterial colony forming and shelf life. The best treatment inhibiting
      bacterial growth for longer was salted eggs soaking in gambier liquid waste :
      water (1:0) 1 h and 25 h with a water content of 62.67%, bacterial colony forming
      0.99 x 1 (0)5 CFU (g-1) and a shelf life 63 days.

PMID- 24897800
TI  - Development and validation of dissolution study of sustained release
      dextromethorphan hydrobromide tablets.
AB  - This study describes the development and validation of dissolution tests for
      sustained release Dextromethorphan hydrobromide tablets using an HPLC method.
      Chromatographic separation was achieved on a C18 column utilizing 0.5%
      triethylamine (pH 7.5) and acetonitrile in the ratio of 50:50. The detection
      wavelength was 280 nm. The method was validated and response was found to be
      linear in the drug concentration range of 10-80 microg mL(-1). The suitable
      conditions were clearly decided after testing sink conditions, dissolution medium
      and agitation intensity. The most excellent dissolution conditions tested, for
      the Dextromethorphan hydrobromide was applied to appraise the dissolution
      profiles. The method was validated and response was found to be linear in the
      drug concentration range of 10-80 microg mL(-1). The method was established to
      have sufficient intermediate precision as similar separation was achieved on
      another instrument handled by different operators. Mean Recovery was 101.82%.
      Intra precisions for three different concentrations were 1.23, 1.10 0.72 and
      1.57, 1.69, 0.95 and inter run precisions were % RSD 0.83, 1.36 and 1.57%,
      respectively. The method was successfully applied for dissolution study of the
      developed Dextromethorphan hydrobromide tablets.

PMID- 24897801
TI  - Bacterial study of fin rot in brown trout by API20E.
AB  - In order to study caudal fin rot with emphasis on Aeromonas sp. and Pseudomonas
      sp. in Salmo trutta caspius from the salmonids propagation and breeding center of
      Shahid Bahonar of kelardasht region, One hundred and eighty brood stocks having
      fin damage symptoms were chosen. Two bacterial samples from each fish were
      cultured on Aeromonas and Pseudomonas specific media. To identify isolated
      bacterial colonies by API20E diagnostic system, samples obtained from bacterial
      cultures 18 to 24 h were prepared and were inoculated into the cupules of test
      strips. At the end of incubation, after addition of reagents if they are
      necessary, the results recorded on the results sheets and were analyzed by Apiwe
      software. The results of API20E diagnostic systems showed that Aeromonas genus
      bacteria including Aeromonas hydrophila with 100% frequency while the bacterial
      genus of Pseudomonas including Pseudomonas fluorescens, Pseudomonas aeruginosa
      and Pseudomonas putida with 36. 84, 31.57 and 21.05% frequency, respectively.
      Also 10.25% of Pseudomonas samples were unidentified.

PMID- 24897802
TI  - In vivo sedative and cytotoxic activities of methanol extract of leaves of
      Crataeva nurvala Buch-Ham.
AB  - The present study was designed to investigate the sedative and cytotoxic
      activities of a crude methanol extract of leaves of Crataeva nurvala Buch-Ham.
      Sedative activity was evaluated by using hole cross, open field and Elevated-Plus
      Maze (EPM) tests at 400 mg kg(-1) body weight. The crude extract decreased the
      locomotor activity of mice in hole cross, open field and EPM tests. The cytotoxic
      activity of this extract was determined by brine shrimp lethality bioassay where
      the LC50 value was found to be 55.46 microg mL(-1) as compared to that of 0.451
      microg mL(-1) exhibited by standard vincristine sulphate. The result shows that
      the crude extract of the leaves of C. nurvala have significant (* p < 0.05)
      sedative and cytotoxic activities.

PMID- 24897803
TI  - Point prevalence of Cryptosporidium oocyst in calves grazing along River Rima
      bank in Sokoto, Nigeria.
AB  - The present study was conducted to investigate the point prevalence of
      Cryptosporidium oocysts infection in calves grazing along the bank of Rima River
      Sokoto in October 2011. The river bank is a converging zone for domestic animals
      reared in different quarters of the town and the surrounding settlements. A total
      number of 2,959 cattle were enumerated out of which 147 (4.97%) were calves.
      Faecal samples were collected from 100 (68.02%) calves by convenient sampling
      technique. Formol-Ether sedimentation and modified Ziehl-Neelsen staining
      techniques were used to identify the Cryptosporidium oocysts in the faecal
      samples. Faecal consistency was also used to identify diarrhoeic and non
      diarrhoeic calves. Cryptosporidium oocysts were identified in 33 (33.0%) of the
      calves examined. The detection rate was higher among the male calves (38.46%)
      than females while the Rahaji breed had the highest prevalence of 62.5%. A total
      of 6 (18.18%) among the positive cases were diarrhoeic. The differences in
      prevalence based on sex, breeds and presence of diarrhoea were not statistically
      significant. Calves may become sources of Cryptosporidia infection to man and
      other animals in the study area through unrestricted movements and interactions
      with the environment.

PMID- 24897804
TI  - Variation of lipid and carbohydrate content in Schizothorax esocinus from Dal
      Lake of Kashmir Valley.
AB  - The present study was designed to measure the monthly and seasonal variation in
      the lipid and carbohydrate content of Schizothorax esocinus. Total lipid content
      of the fish was measured by Folch's method and the carbohydrate content was
      evaluated by Dubois method. The lipid content of Schizothorax esocinus varied
      seasonally, with maxima and minima in a year. The highest lipid content (0.45 g
      g(-1)) was measured in the July and the lowest lipid content (0.25 g g(-1)) in
      November. Evaluating the proximate composition of fish is important aspect in
      fish nutrition. The carbohydrate does not vary so much with a slight increase in
      spring (0.18%) and a slight decrease in autumn season (0.10%) with an average
      value of 0.14%. Total protein profile was also carried out in different organs of
      the fish by using SDS PAGE. The fish is a good source of lipid, carbohydrate and
      proteins, required for the balanced diet of human consumption.

PMID- 24897805
TI  - Patient autonomy or patient confusion?

PMID- 24897806
TI  - African mass circumcision programmes: a dangerous distraction.

PMID- 24897807
TI  - Reducing the surgical complications of smoking by cotinine testing.

PMID- 24897808
TI  - A path to full-service contracting with general practitioners under National
      Health Insurance.

PMID- 24897809
TI  - Primary prevention of rheumatic fever in children: key factors to consider.

PMID- 24897811
TI  - A balanced approach to interpreting the WHIRCDMT.

PMID- 24897812
TI  - From coal-face clinicians to change agents--igniting healthcare innovation.

PMID- 24897810
TI  - Irlam et al. respond.

PMID- 24897813
TI  - Annually, 1% of gold miners die--4% sent home sick.

PMID- 24897814
TI  - Clinical access to Bedaquiline Programme for the treatment of drug-resistant
      tuberculosis.
AB  - While clinical disease caused by drug-sensitive Mycobacterium tuberculosis (MTB)
      can usually be treated successfully, clinical disease caused by drug-insensitive
      MTB is associated with a poorer prognosis. In December 2012, a new drug,
      bedaquiline, was approved by the US Food and Drug Administration. This article
      documents the process whereby the National Department of Health, Right to Care
      and Medecins Sans Frontieres obtained access to this medication for South
      Africans who might benefit from subsequent implementation of the Clinical Access
      to Bedaquiline Programme.

PMID- 24897815
TI  - Recommendations pertaining to the use of viral vaccines: influenza 2014.
AB  - Here we provide recommendations for the use of viral vaccines in anticipation of
      the 2014 southern hemisphere influenza season. For a review of the 2013 influenza
      season, please refer to the National Institute for Communicable Diseases,
      National Health Laboratory Service website (http://www.nicd.ac.za).

PMID- 24897816
TI  - Cardiovascular prevention: lifestyle and statins--competitors or companions?
AB  - Favourable lifestyles promote cardiovascular protection. Exercise can induce
      beneficial changes in the genome that decrease low-density lipoprotein
      cholesterol (LDL-C) and increase anti-inflammatory markers. The Mediterranean
      dietary pattern, fortified by nuts, while not reducing weight, reduces mortality.
      Lifestyle changes combined with statin therapy provide potent protection against
      coronary heart disease, especially when used for secondary prevention after
      cardiovascular events. Decisions regarding the initiation of statin therapy for
      primary prevention are more difficult, requiring consideration of both the LDL-C
      level and the degree of cardiovascular risk for dyslipidaemic patients. Combining
      intensive exercise and statin therapy substantially reduces the mortality risk,
      and thus is potentially the ideal risk-reducing combination.

PMID- 24897818
TI  - The research ethics evolution: from Nuremberg to Helsinki.
AB  - Health research sets out to acquire not only theoretical knowledge but also
      benefits for many people and often society as a whole, and is therefore
      justified. The quandary, though, is how such an important, shared purpose can be
      pursued with full protection of individuals and communities, in particular those
      with vulnerabilities. Abuses in the field surfaced in the early 1800s, and by the
      1890s, anti-vivisectionists were calling for laws to protect children because of
      the increasing numbers of institutionalised children being subjected to unethical
      research. When read together, the Nuremberg Code and the Universal Declaration of
      Human Rights can be interpreted as establishing a basis for underpinning the
      principles of free and informed consent and avoiding harms and exploitation in
      scientific experiments involving human participants. The Declaration of Helsinki
      has been recognised as one of the most authoritative statements on ethical
      standards for human research in the world.

PMID- 24897817
TI  - Isoniazid preventive therapy for tuberculosis in South Africa: an assessment of
      the local evidence base.
AB  - Worldwide, South Africa (SA) has the worst tuberculosis (TB) epidemic. In SA,
      there are > 6.1 million people living with HIV (PLWH) and the country now has the
      largest antiretroviral treatment programme with > 2 million people receiving
      combination therapy. While there has been a marked recent decline in HIV
      associated deaths, > 50% of TB cases still continue to be diagnosed in PWLH. The
      current TB control strategy based on passive case finding, chemotherapy of
      childhood TB contacts and directly observed therapy has clearly failed to control
      endemic TB in SA. Two recent meta-analyses have shown a > 60% reduction in TB in
      HIV-infected adults after isoniazid preventive therapy (IPT). SA has implemented
      the World Health Organization policy and IPT is now recommended for HIV-positive
      people for up to 36 months. Originally, there was only one SA study included in
      the evidence base supporting this policy, but subsequently four randomised
      controlled trials have been conducted in SA populations. These studies, together
      with local observational studies, are the subject of this local, evidence-based
      review.

PMID- 24897819
TI  - New imaging approaches for improving diagnosis of childhood tuberculosis.

PMID- 24897820
TI  - Systematic review of the evidence for rational dosing of colistin.
AB  - BACKGROUND: There is an alarming global increase in the incidence of nosocomial
      infections with multidrug-resistant Gram-negative bacteria, which are often only
      susceptible to colistin. Colistin was developed prior to current methods of
      establishing dosing using pharmacokinetic-pharmacodynamic relationships. Dosing
      regimens differ in package inserts from different manufacturers and in different
      guidelines. It is imperative to avoid under-dosing with colistin in order to
      limit the development of resistance, as it is the last line of defence. METHODS:
      We conducted a systematic review of the literature to develop guidelines for
      rational dosing of intravenous colistin, with a particular focus on critically
      ill patients. RESULTS: Colistin is administered as the inactive pro-drug
      colistimethate sodium. Colistin demonstrates concentration-dependent bacterial
      killing, suggesting that higher doses should be administered less frequently to
      achieve higher peak concentrations. Dose-related nephrotoxicity occurs, making it
      impossible to safely achieve concentrations that prevent the selection of
      resistant mutants or the effective eradication of bacteria with higher minimum
      inhibitory concentrations. Theoretically, combination therapy should be used to
      reduce the risk of selection of resistant bacteria. In critically ill patients, a
      loading dose should be given to rapidly achieve therapeutic concentrations,
      followed by maintenance doses of 4.5 MU 12-hourly. Maintenance dose adjustment is
      necessary with renal impairment. CONCLUSION: Easier access to colistin is needed
      in South Africa, where it is not a registered medicine. Further research is
      needed to better characterise colistin's pharmacokinetic-pharmacodynamic
      relationships in humans and to establish whether combinations of colistin with
      other antimicrobials result in improved clinical outcomes or a reduction in
      selection of resistant bacteria.

PMID- 24897821
TI  - Determinants, outcomes and costs of ceftriaxone v. amoxicillin-clavulanate in the
      treatment of community-acquired pneumonia at Witbank Hospital.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of death and
      morbidity worldwide. Treatment is centred on antibiotics with ceftriaxone and
      amoxicillin-clavulanate being some of the most commonly prescribed agents.
      OBJECTIVE: To compare treatment outcomes and costs in patients receiving either
      of these two antibiotics at Witbank Hospital (WH). METHODS: A total of 200
      randomly selected adult patient files (100 receiving ceftriaxone and 100
      amoxicillin-clavulanate) recording a diagnosis of CAP were studied to determine
      the length of hospital stay, comorbid conditions and treatment outcomes. A
      descriptive and comparable analysis was performed. RESULTS: Male gender, higher
      CURB-65 scores and death were associated with the use of ceftriaxone. Severity of
      disease and previous antibiotic exposure influenced the duration of hospital
      admission. CONCLUSION: Gender and severity of disease (based on the CURB-65
      score) were the determinants of antibiotic choice at WH. Male gender increased
      the likelihood of being treated with ceftriaxone, as did a CURB-65 score of > 2.
      There were no differences in the outcomes of CAP patients treated with
      ceftriaxone compared with those treated with amoxicillin-clavulanate.
      Irrespective of antibiotic used, gender and severity of disease influenced
      treatment outcomes. Male gender was associated with a higher mortality and longer
      hospital stay. The average duration of stay for both antibiotics was not
      significantly different. Thus, only level 1 and 2 costs need to be considered
      when comparing the two regimens. On this basis, ceftriaxone was cheaper than
      amoxicillin-clavulanate.

PMID- 24897822
TI  - The impact of chronic pseudomonal infection on pulmonary function testing in
      individuals with cystic fibrosis in Pretoria, South Africa.
AB  - BACKGROUND: Colonisation of the airway by Pseudomonas spp. in cystic fibrosis has
      been reported to be an important determinant of decline in pulmonary function.
      OBJECTIVE: To assess pulmonary function decline and the presence of bacterial
      colonisation in patients with cystic fibrosis (CF) attending a CF clinic in a
      developing country. METHODS: A retrospective audit of patients attending the CF
      clinic at Steve Biko Academic Hospital, Pretoria, South Africa, was performed.
      The data included spirometric indices and organisms routinely cultured from
      airway secretions (Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA)).
      RESULTS: There were 29 study subjects. Analysis of variance for ranks (after
      determining that baseline pulmonary function, age, gender and period of follow-up
      were not contributing to pulmonary function decline) revealed a median decline in
      forced expiratory volume in 1 second, forced vital capacity and forced expiratory
      flow over 25 - 75% expiration of 12%, 6% and 3%, respectively, for individuals
      colonised by PA. There was no pulmonary function decline in individuals not
      colonised by PA, or in individuals colonised by SA. CONCLUSION: Pulmonary
      function decline in this South African centre is significantly influenced by
      chronic pseudomonal infection. Other influences on this phenomenon should be
      explored.

PMID- 24897823
TI  - Cardiometabolic markers to identify cardiovascular disease risk in HIV-infected
      black South Africans.
AB  - BACKGROUND: The prevalence of HIV is the highest in sub-Saharan Africa; South
      Africa (SA) is one of the most affected countries with the highest number of
      adults living with HIV infection in the world. Besides the traditional risk
      factors for cardiovascular disease (CVD) in the general population, in people
      living with HIV there are specific factors - chronic inflammation, metabolic
      changes associated with the infection, therapy, and lipodystrophy - that
      potentially increase the risk for developing CVD. OBJECTIVE: This study proposes
      a screening discriminant model to identify the most important risk factors for
      the development of CVD in a cohort of 140 HIV-infected black Africans from the
      North West Province, SA. METHODS: Anthropometric measures, systolic blood
      pressure, diastolic blood pressure and the carotid-dorsalis pedis pulse wave
      velocity were determined. Blood was analysed to determine the levels of total
      cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol, triglycerides (TGs) and glucose. Partial least squares
      discriminant analysis was performed as a supervised pattern recognition method.
      Independent Student's t-tests were further employed to compare the means of risk
      factors on interval scales; for comparison of categorical risk factors between
      groups, chi2 tests were used. RESULTS: A TG:HDL-C ratio > or = 1.49, TC:HDL-C
      ratio > or = 5.4 and an HDL-C level < or = 0.76 mmol/l indicated CVD risk in this
      cohort of patients living with HIV. CONCLUSION: The results have important health
      implications for black Africans living with HIV as these lipid levels may be a
      useful indicator of the risk for CVD.

PMID- 24897824
TI  - High pleural fluid adenosine deaminase levels: a valuable tool for rapid
      diagnosis of pleural TB in a middle-income country with a high TB/HIV burden.
AB  - BACKGROUND: South Africa has the highest burden of tuberculosis (TB) in the World
      Health Organization (WHO) African region. Using traditional TB diagnostic tools,
      the diagnosis of pleural TB (PTB) is highly unrewarding. Elevated levels of
      pleural fluid adenosine deaminase (FADA) have been shown to be useful in the
      diagnosis of PTB; however, similar levels may be found in some other medical
      conditions leading to misdiagnosis. Following queries from clinicians concerning
      the likely high false-positive (FP) rate of FADA from our laboratory, we
      performed a retrospective audit of all high FADA results generated over a 12
      month period. OBJECTIVES: To determine the positive predictive value (PPV) of
      FADA, the frequent causes of FPs in our laboratory and the demographic
      characteristics of tuberculous pleural effusions (TPEs) and non-tuberculous
      pleural effusions (NTPEs). METHODS: High FADA results generated in the past year
      were extracted with corresponding TB culture results, fluid cell count, cytology/
      histology results, radiology reports and HIV results. Hospital records were
      reviewed for the final diagnosis in each case. Diagnosis of PTB was based on the
      WHO case definition of TB. RESULTS: A total of 159 results were reviewed: 133
      (83.6%) were TPE, hence FADA had a PPV of 83.6%. Neoplasm was the most common
      cause of an FP in 13/26 (50%) NTPEs. While TPE was more common than NTPE in
      younger people, both groups had an equal gender distribution. CONCLUSION: FADA
      had a high PPV for PTB in our laboratory. We recommend its continued use as a
      rapid and reliable diagnostic tool for PTB.

PMID- 24897825
TI  - Integration of TB and ART services fails to improve TB treatment outcomes:
      comparison of ART/TB primary healthcare services in Cape Town, South Africa.
AB  - BACKGROUND: The combined tuberculosis (TB) and HIV epidemics in South Africa (SA)
      have created enormous operational challenges for a health service that has
      traditionally run vertical programmes for TB treatment and antiretroviral therapy
      (ART) in separate facilities. This is particularly problematic for TB/HIV co
      infected patients who need to access both services. OBJECTIVE: To determine
      whether integrated TB facilities had better TB treatment outcomes than single
      service facilities in Cape Town, SA. METHODS: TB treatment outcomes were
      determined for newly registered, adult TB patients (aged > or = 18 years) at 13
      integrated ART/TB primary healthcare (PHC) facilities and four single-service PHC
      facilities from 1 January 2009 to 30 June 2010. A chi2 test adjusted for a
      cluster sample design was used to compare outcomes by type of facility. RESULTS:
      Of 13,542 newly registered patients, 10,030 received TB treatment in integrated
      facilities and 3,512 in single-service facilities. There was no difference in
      baseline characteristics between the two groups with HIV status determined for
      9,351 (93.2%) and 3,227 (91.9%) patients, of whom 6 649 (66.3%) and 2,213 (63%)
      were HIV-positive in integrated facilities and single-service facilities,
      respectively. The median CD4+ count of HIV-positive patients was 152 cells/microl
      (interquartile range (IQR) 71-277) for integrated facilities and 148 cells/microl
      (IQR 67-260) for single-service facilities. There was no statistical difference
      in the TB treatment outcome profile between integrated and single-service
      facilities for all TB patients (p = 0.56) or for the sub-set of HIV-positive TB
      patients (p = 0.58) CONCLUSION: This study did not demonstrate improved TB
      treatment outcomes in integrated PHC facilities and showed that the provision of
      ART in the same facility as TB services was not associated with lower TB death
      and default rates.

PMID- 24897827
TI  - Spina bifida: a few simple facts about a complex condition.

PMID- 24897826
TI  - Tuberculosis incidence in Cameroonian prisons: a 1-year prospective study.
AB  - BACKGROUND: Rates of tuberculosis (TB) transmission in prisons are reported to be
      high worldwide. However, a recent systematic review identified only 19 published
      studies reporting TB incidence in prisons, most of them from the last century and
      only one from sub-Saharan Africa. OBJECTIVES: To assess the persisting risk of
      smear-positive pulmonary tuberculosis (PTB) among prison populations benefiting
      from a comprehensive TB/HIV control programme in Cameroon, compared with that in
      the community. METHODS: This descriptive and prospective study evaluated PTB
      incidence rates over a 1-year period. The study population was inmates of 10
      major prisons, sampled by convenience, comprising about 45% of the country's
      prison population. As PTB incident cases, all prisoners with incident PTB after a
      prison stay of > or = 90 days were considered. The prison TB incidence rate was
      compared with that of the corresponding male population in the community.
      RESULTS: The mean annual PTB incidence in Cameroonian prisons in this study was 1
      700 cases in 100 000 person-years at risk, the incidence rate ratio being 9.4
      (95% confidence interval 8.1-10.9). CONCLUSION: Findings suggest that
      internationally recommended prison TB control measures alone may not help protect
      prisoners from within-prison spread of TB. Imprisonment policies and conditions
      therefore require fundamental changes.

PMID- 24897828
TI  - Spina bifida: a multidisciplinary perspective on a many-faceted condition.
AB  - Open spina bifida or myelomeningocele (SBM) is the most common birth defect
      involving the central nervous system, second only in incidence to congenital
      cardiac disease. Outcomes in this disorder were poor until the mid-20th century,
      when modern neurosurgical techniques (closing the lesion and treating
      hydrocephalus) and treatment for the neuropathic bladder addressed the major
      causes of mortality, although SBM may still be poorly treated in the developing
      world. Initial management - or mismanagement - has a profound impact on survival
      and long-term quality of life.

PMID- 24897830
TI  - Talking about tobacco.

PMID- 24897829
TI  - The 2014 Retirement Confidence Survey: confidence rebounds--for those with
      retirement plans.

PMID- 24897831
TI  - Individualisation of care and the obesity paradox.
AB  - The obesity 'paradox' has recently been discussed based upon the observation that
      although obesity may be a major causative factor in certain conditions, its
      presence appears to be protective once that condition occurs. There is a growing
      body of persuasive evidence to support the obesity paradox in diseases including
      renal failure and heart failure. Recent evidence is reliable, adjusting more
      effectively for confounders such as smoking and intercurrent illness, which make
      lower weight an unhealthy state. The existence of the paradox highlights the fact
      that approaches to weight management are not as simple as inducing the loss of a
      few kilograms in overweight and obese individuals, and emphasises the importance
      of individualisation of care in obesity management taking into account age,
      ethnicity and comorbid illness. This article explores the individualisation of
      care in obesity, drawing attention to the obesity paradox in particular.

PMID- 24897832
TI  - Capturing district nursing through a knowledge-based electronic caseload analysis
      tool (eCAT).
AB  - The Electronic Caseload Analysis Tool (eCAT) is a knowledge-based software tool
      to assist the caseload analysis process. The tool provides a wide range of
      graphical reports, along with an integrated clinical advisor, to assist district
      nurses, team leaders, operational and strategic managers with caseload analysis
      by describing, comparing and benchmarking district nursing practice in the
      context of population need, staff resources, and service structure. District
      nurses and clinical lead nurses in Northern Ireland developed the tool, along
      with academic colleagues from the University of Ulster, working in partnership
      with a leading software company. The aim was to use the eCAT tool to identify the
      nursing need of local populations, along with the variances in district nursing
      practice, and match the workforce accordingly. This article reviews the
      literature, describes the eCAT solution and discusses the impact of eCAT on
      nursing practice, staff allocation, service delivery and workforce planning,
      using fictitious exemplars and a post-implementation evaluation from the trusts.

PMID- 24897833
TI  - Social isolation and loneliness in the elderly: an exploration of some of the
      issues.
AB  - Older people are more vulnerable to loneliness and social isolation, and are more
      at risk of a range of health and social issues which can be directly linked to
      loneliness. However, there are often complex problems which are unique to the
      older age group which can have a profound effect on the provision and budgets of
      both health and social care. Various schemes have been put in place across the
      country to try to reduce the effects of loneliness and there is some evidence to
      support the mentoring and befriending models, although more research would
      provide clarity regarding their effectiveness.

PMID- 24897834
TI  - A practice-based survey of patients dying in hospital: can we do more to support
      end-of-life care at home?
AB  - An analysis of patients dying in hospital was carried out in a practice. The
      research showed that patients with non-malignant disease are overrepresented.
      Despite good district nurse support, identifying those likely to die and
      predicting death is more difficult than with cancer. There is a high rate of
      admission from nursing homes, and a reluctance by patients and relatives to
      discuss likely death is mirrored by uncertainty among clinicians.

PMID- 24897835
TI  - Disrupted social connectedness in people with Parkinson's disease.
AB  - A study was conducted to explore the effects of Parkinson's disease on people's
      social interactions. An exploratory qualitative design was used. Participants
      were a purposive sample of 10 people with Parkinson's disease who were attending
      a hospital outpatients' neurology clinic. Data were collected by semi-structured
      in-depth interviews. All interviews were transcribed and analysed by using
      conventional content analysis to explore the participants' experiences and
      perceptions on social interactions, using the central question 'what effect does
      Parkinson's disease have on people's social interactions?' Analysis revealed that
      Parkinson's disease affected social interactions by disrupting social
      connectedness. Social connectedness was disrupted by a number of factors,
      including 'progressive physical disability, mood disturbances, shrinking of
      social activities and secluding oneself. Older adults with Parkinson's disease
      therefore face a number of challenges to remaining socially connected. It appears
      that disrupted social connectedness is one of the negative consequences of living
      with Parkinson's.

PMID- 24897836
TI  - Community nurses supporting carers: a new online resource from the Queen's
      Nursing Institute.

PMID- 24897837
TI  - Disclosing personal health information relating to adults who lack capacity.
AB  - The need to share information about patients is vital to effective care and
      protection, especially where it relates to adults who lack decision-making
      capacity but it has to be balanced against the right to confidentiality. Like
      other health professionals, district nurses have a duty to maintain the
      confidentiality of patient information, and incapable adults have the right to
      expect their personal health information to be kept private. This right is
      guaranteed by the common-law duty of confidence, the Data Protection Act 1998 and
      the NHS Care Record Guarantee and confidentiality policy. This article discusses
      the district nurse's legal obligations when considering sharing information in
      relation to an incapable adult

PMID- 24897838
TI  - Sexuality in palliative care: more than sex.

PMID- 24897839
TI  - Continuing to learn from Francis.

PMID- 24897840
TI  - To the editor: Misstatements concerning forensic entomology practice in recent
      publications.

PMID- 24897841
TI  - Reply: A correspondence from a maturing discipline.

PMID- 24897842
TI  - Reply: Commentary on letter to the editor from Jeffrey Wells.

PMID- 24897843
TI  - Reply: On throwing out the baby with the bathwater: a reply to Wells.

PMID- 24897844
TI  - The impact of temperature on the bionomics of Aedes (Stegomyia) aegypti, with
      special reference to the cool geographic range margins.
AB  - The mosquito Aedes (Stegomyia) aegypti (L.), which occurs widely in the
      subtropics and tropics, is the primary urban vector of dengue and yellow fever
      viruses, and an important vector of chikungunya virus. There is substantial
      interest in how climate change may impact the bionomics and pathogen transmission
      potential of this mosquito. This Forum article focuses specifically on the
      effects of temperature on the bionomics of Ae. aegypti, with special emphasis on
      the cool geographic range margins where future rising temperatures could
      facilitate population growth. Key aims are to: 1) broadly define intra-annual
      (seasonal) patterns of occurrence and abundance of Ae. aegypti, and their
      relation to climate conditions; 2) synthesize the existing quantitative knowledge
      of how temperature impacts the bionomics of different life stages of Ae. aegypti;
      3) better define the temperature ranges for which existing population dynamics
      models for Ae. aegypti are likely to produce robust predictions; 4) explore
      potential impacts of climate warming on human risk for exposure to Ae. aegypti at
      its cool range margins; and 5) identify knowledge or data gaps that hinder our
      ability to predict risk of human exposure to Ae. aegypti at the cool margins of
      its geographic range now and in the future. We first outline basic scenarios for
      intra-annual occurrence and abundance patterns for Ae. aegypti, and then show
      that these scenarios segregate with regard to climate conditions in selected
      cities where they occur. We then review how near-constant and intentionally
      fluctuating temperatures impact development times and survival of eggs and
      immatures. A subset of data, generated in controlled experimental studies, from
      the published literature is used to plot development rates and survival of eggs,
      larvae, and pupae in relation to water temperature. The general shape of the
      relationship between water temperature and development rate is similar for eggs,
      larvae, and pupae. Once the lower developmental zero temperature (10-14 degrees
      C) is exceeded, there is a near-linear relationship up to 30 degrees C. Above
      this temperature, the development rate is relatively stable or even decreases
      slightly before falling dramatically near the upper developmental zero
      temperature, which occurs at -38-42 degrees C. Based on life stage-specific
      linear relationships between water temperature and development rate in the 15-28
      degrees C range, the lower developmental zero temperature is estimated to be 14.0
      degrees C for eggs, 11.8 degrees C for larvae, and 10.3 degrees C for pupae. We
      further conclude that available population dynamics models for Ae. aegypti, such
      as CIMSiM and Skeeter Buster, likely produce robust predictions based on water
      temperatures in the 16-35 degrees C range, which includes the geographic areas
      where Ae. aegypti and its associated pathogens present the greatest threat to
      human health, but that they may be less reliable in cool range margins where
      water temperatures regularly fall below 15 degrees C. Finally, we identify
      knowledge or data gaps that hinder our ability to predict risk of human exposure
      to Ae. aegypti at the cool margins of its range, now and in the future, based on
      impacts on mosquito population dynamics of temperature and other important
      factors, such as water nutrient content, larval density, presence of biological
      competitors, and human behavior.

PMID- 24897845
TI  - A new species of Simulium (Gomphostilbia) (Diptera: Simuliidae) from Malaysia,
      with keys to 32 species of the Simulium ceylonicum species-group.
AB  - Simulium (Gomphostilbia) leparense sp. nov. is described from females, males, and
      pupae collected from Peninsular Malaysia. This new species is assigned to the
      ceylonicum species-group of the subgenus Gomphostilbia, and is characterized by
      the female and male scuta covered with dark-brown short hairs, smaller number of
      male upper-eye facets, presence of shiny paired spots on the male abdominal
      segments 2-8, and absence of grapnel-shaped hooklets on the pupal abdominal
      segment 9. The male and pupa of S. capillatum Takaoka, which was originally
      described from larvae collected from Sarawak and Sabah, are described for the
      first time. Keys to identify all 32 species of the Simulium ceylonicum species
      group including 27 species from other countries are provided for females, males,
      pupae, and mature larvae.

PMID- 24897846
TI  - New species of the feather mite family Proctophyllodidae (Acariformes: Astigmata)
      from two species of mockingbirds (Passeriformes: Mimidae) in eastern North
      America.
AB  - Four new species of the feather mite family Proctophyllodidae are described from
      two species of the family Mimidae (Passeriformes): Proctophyllodes apanaskevichi
      sp. n. (Proctophyllodinae) and Amerodectes dumetellae sp. n. (Pterodectinae) from
      the Gray Catbird, Dumetella carolinensis (L., 1766), and Proctophyllodes
      gallowayi sp. n. (Proctophyllodinae) and Metapterodectes toxostomae sp. n.
      (Pterodectinae) from the Brown Thrasher, Toxostoma rufum (L., 1758). A.
      dumetellae and M. toxostomae represent the first records of mites of the
      subfamily Pterodectinae on mockingbirds.

PMID- 24897847
TI  - Do agonistic interactions underlie the segregation and relative abundances
      between two Loxosceles species (Araneae: Sicariidae)?
AB  - The medically important spiders Loxosceles intermedia Mello-Leitao and Loxosceles
      laeta (Nicolet) are segregated in Curitiba, southern Brazil, where L. intermedia
      is more abundant and widespread than L. laeta. Because they share similar
      microhabitat preferences and wander in search of web sites, agonistic encounters
      are likely to occur. The purposes of this study were to describe agonistic
      interactions and interpret their consequences for the relative abundances and
      spatial segregation of L. intermedia and L. laeta. Experimental contests were
      performed between residents and intruders. Asymmetries between contestants
      included sex, age, species, weight, and residence status. Nine behavioral
      categories were defined. Through discriminant analyses, it was possible to
      differentiate spider sex, species, and residence based on their agonistic
      behaviors. Intruders, juveniles, and L. intermedia individuals were better
      characterized by exploratory behaviors, whereas L. laeta females were
      differentiated by aggressiveness. By performing a multiple logistic regression,
      with winning or defeat as a dependent variable of sex, age, species, size,
      weight, and residence, it was possible to say that residents and L. intermedia
      individuals had the highest winning odds in contests, whereas juveniles had lower
      winning odds than adults. Advantages of the prior residence may help to explain
      the predominance of L. laeta in old colonization sites, whereas the higher
      winning odds of L. intermedia and less aggressive behavior toward conspecifics
      may lead to a successful establishment of dense populations in new sites. A
      better understanding of agonistic interactions as a mechanism of spacing,
      segregation, and species replacement among spiders may be helpful for control
      purposes.

PMID- 24897848
TI  - Distribution of Culicoides sonorensis (Diptera: Ceratopogonidae) in Alberta,
      Canada.
AB  - The distribution of Culicoides sonorensis Wirth and Jones was examined in
      Alberta, Canada. Sampling was conducted weekly using blacklight traps at eight
      locations in 2009, and 10 locations during 2010-2012. Nine supplemental sites
      were sampled twice annually during both 2011 and 2012. Abundance of C. sonorensis
      was consistently greatest at a site near the U.S. border, and declined in a
      northerly direction. Mean annual abundance at this site ranged from 6.4- to >
      1,000-fold greater across positive sites. Data from a less extensive survey
      conducted during 2002-2006 were included in the remaining analyses. C. sonorensis
      was distributed below a diagonal spanning 49 degrees 30' N, 113 degrees 0' W to
      51 degrees 21' N, 110 degrees 40' W. The relationship between the proportion of
      weekly samples positive and mean annual abundance at a site was determined and
      indicated that the proportion of positive samples could be used as a surrogate
      measure of abundance to overcome issues associated with the extreme variation in
      abundance. A series of logistic regression models were developed and evaluated to
      determine the effects of spatial (latitude and longitude), climatic (historic
      temperature and precipitation during the warmest quarter), and weather
      (temperature during the sample interval and spring precipitation) on abundance as
      measured by the proportion of positive samples. Spatial and climatic variables
      set the overall level of abundance, while weather variables added seasonal
      fluctuations within years, and also fluctuations between years. These data will
      be useful for long-term monitoring of C. sonorensis and as a baseline for
      detecting shifts in abundance that might occur because of climate change.

PMID- 24897849
TI  - Impact of climate change on the distribution of Aedes albopictus (Diptera:
      Culicidae) in northern Japan: retrospective analyses.
AB  - The impact of climate change on the distribution of Aedes albopictus (Skuse) was
      analyzed in northern Japan, where chronological distribution records are
      incomplete. We analyzed local climate data using linear regression of the thermal
      suitability index (TSI) for the mosquito and mean annual temperature as functions
      of time. In northern Japan, thermal conditions since the early 20th century have
      become increasingly suitable for Ae. albopictus, more as a result of decreasing
      coldness in the overwintering season than increasing warmth in the reproductive
      season. Based on recent discovery records of Ae. albopictus in the northern
      border range, we determined thermal criteria for estimating when its persistent
      establishment became thermally possible. Retrospective analyses indicated that
      those criteria were reached in most coastal lowlands of northern Honshu before
      the accelerated temperature increase after the mid-1980s and the first records of
      this species after 1990; at some sites, temperature criteria were reached during
      or before the early 20th century. Expansion of the thermally suitable range after
      1990 was supported only for inland areas and the northernmost Pacific coast. The
      estimated expansion rate was approximately 26 km per decade. Our analyses also
      demonstrated the importance of local climate heterogeneity (apart from north
      south or altitudinal temperature gradients) in determining the expansion pattern.

PMID- 24897850
TI  - Delayed egg hatching of Anopheles gambiae (Diptera: Culicidae) pending water
      agitation.
AB  - Mosquito eggs laid on water surfaces typically hatch spontaneously soon after the
      embryos within them become fully formed first-instar larvae. However, we have
      found that Anopheles gambiae Giles, an important vector of malaria in Africa,
      exhibits delayed hatching until the water surface is agitated, a feature
      overlooked in most laboratory colonies. Agitation within 24 h postoviposition,
      before embryonation was complete, failed to stimulate delayed postembryonic
      hatching of isolated eggs on the following day (day 2), when < 1% had hatched
      spontaneously. However, 5 min of water agitation of these dormant pharate first
      instar larvae on day 2 resulted in an almost immediate hatch of 63.3 versus 0% of
      nonagitated controls, plus another 3.9 versus 0.3%, respectively, during the
      following 24 h. With daily agitation, installment hatching occurred mainly during
      2-6 d postoviposition. The mean cumulative hatch after 7 d of daily agitation was
      83.1 versus 1.1% of nonagitated eggs. Experiments with eggs in groups
      demonstrated that egg density and activity of already-hatched larvae had no
      stimulatory effect. Eggs stored 1-4 wk at 25.5 or at 15.5 degrees C, and then
      agitated daily for 6 d at 25.5 degrees C, showed a gradual decline in viability.
      Viability was sustained longer at the lower temperature. Implications of
      agitation-induced egg hatching for rainy-season and dry-season ecology of An.
      gambiae are discussed. Suspended hatching and cool storage already are proving
      convenient for efficient mass rearing and accurate modeling of weather-based
      population dynamics.

PMID- 24897851
TI  - Volatiles from waste larval rearing media attract gravid screwworm flies
      (Diptera: Calliphoridae) to oviposit.
AB  - Gravid screwworm flies, Cochliomyia hominivorax (Coquerel), are attracted to the
      volatiles from waste larval rearing media to deposit eggs. Studies were conducted
      to identify volatile chemicals from the waste larval media and determine their
      effectiveness to attract gravid flies to oviposit. Volatiles were collected using
      solid-phase microextraction method, and five active chemicals, namely, dimethyl
      disulfide, dimethyl trisulfide, phenol, p-cresol, and indole, were identified
      using gas chromatography-mass spectrometry. In electroantennography studies,
      antennae ofgravid screwworm flies, Cochliomyia macellaria (F.), responded
      positively to each of the identified compounds. A synthetic blend of these five
      compounds in the ratio of 335:200:57:1:12 was prepared and tested for its
      effectiveness to attract both C. hominivorax and C. macellaria using laboratory
      bioassay methods. Significantly more gravid C. macellaria were attracted to and
      landed on substrates treated with 10-fold diluted blends compared with those
      landed on substrates treated with ethanol only (as control). Only a few young
      females and young and old males were attracted to the substrates treated with the
      synthetic blend. The C. hominivorax females laid significantly more eggs on
      substrates treated with waste media, 10-fold diluted blend, and 100-fold diluted
      blend than on substrates with undiluted blend or ethanol. Similarly, C.
      macellaria deposited significantly more eggs on substrates treated with waste
      media, 10-fold diluted blend, and 100-fold diluted blend compared with substrates
      with undiluted blend or ethanol. C. macellaria females deposited significantly
      less amount of eggs than did C. hominivorax females. These results indicate that
      the synthetic blend of five compounds identified may serve as an oviposition
      attractant for C. hominivorax as well as for C. macellaria.

PMID- 24897852
TI  - Microhabitat partitioning of Aedes simpsoni (Diptera: Culicidae).
AB  - Yellow fever virus is a reemerging infection responsible for widespread, sporadic
      outbreaks across Africa. Although Aedes aegypti (L.) is the most important vector
      globally, in East Africa, epidemics may be vectored by Aedes bromeliae
      (Theobald), a member of the Aedes simpsoni (Theobald) species complex. The Ae.
      simpsoni complex contains 10 subspecies, of which Ae. bromeliae alone has been
      incriminated as a vector of yellow fever virus. However, morphological markers
      cannot distinguish Ae. bromeliae from conspecifics, including the sympatric and
      non-anthropophilic Aedes lilii (Theobald). Here, we used three sequenced nuclear
      markers to examine the population structure of Ae. simpsoni complex mosquitoes
      collected from diverse habitats in Rabai, Kenya. Gene trees consistently show
      strong support for the existence of two clades in Rabai, with segregation by
      habitat. Domestic mosquitoes segregate separately from forest-collected
      mosquitoes, providing evidence of habitat partitioning on a small spatial scale
      (< 5 km). Although speculative, these likely represent what have been described
      as Ae. bromeliae and Ae. lilii, respectively. The observation of high levels of
      diversity within Rabai indicates that this species complex may exhibit
      significant genetic differentiation across East Africa. The genetic structure,
      ecology, and range of this important disease vector are surprisingly understudied
      and need to be further characterized.

PMID- 24897853
TI  - Transcriptional analysis of four family 4 P450s in a Puerto Rico strain of Aedes
      aegypti (Diptera: Culicidae) compared with an Orlando strain and their possible
      functional roles in permethrin resistance.
AB  - A field strain of Aedes aegypti (L.) was collected from Puerto Rico in October
      2008. Based on LD50 values by topical application, the Puerto Rico strain was 73
      fold resistant to permethrin compared with a susceptible Orlando strain. In the
      presence of piperonyl butoxide, the resistance of Puerto Rico strain of Ae.
      aegypti was reduced to 15-fold, suggesting that cytochrome P450-mediated
      detoxification is involved in the resistance of the Puerto Rico strain to
      permethrin. To determine the cytochrome P450s that might play a role in the
      resistance to permethrin, the transcriptional levels of 164 cytochrome P450 genes
      in the Puerto Rico strain were compared with that in the Orlando strain. Of the
      164 cytochrome P450s, 33 were significantly (P < 0.05) up-regulated, including
      cytochrome P450s in families four, six, and nine. Multiple studies have
      investigated the functionality of family six and nine cytochrome P450s,
      therefore, we focused on the up-regulated family 4 cytochrome P450s. To determine
      whether up-regulation of the four cytochrome P450s had any functional role in
      permethrin resistance, transgenic Drosophila melanogaster Meigen lines
      overexpressing the four family 4 P450 genes were generated, and their ability to
      survive exposure to permethrin was evaluated. When exposed to 5 microg per vial
      permethrin, transgenic D. melanogaster expressing CYP4D24, CYP4H29, CYP4J15v1,
      and CYP4H33 had a survival rate of 60.0 +/- 6.7, 29.0 +/- 4.4, 64.4 +/- 9.7, and
      11.0 +/- 4.4%, respectively. However, none of the control flies survived the
      permethrin exposure at the same concentration. Similarly, none of the transgenic
      D. melanogaster expressing CYP4J15v1 or CYP4H33 ?5 survived when they were
      exposed to permethrin at 10 microg per vial. However, transgenic D. melanogaster
      expressing CYP4D24 and CYP4H29 had a survival rate of 37.8 +/- 4.4 and 2.2 +/-
      2.2%, respectively. Taken together, our results suggest that CYP4D24 might play
      an important role in cytochrome P450-mediated resistance to permethrin.

PMID- 24897855
TI  - Solvent, drying time, and substrate affect the responses of lone star ticks
      (Acari: Ixodidae) to the repellents deet and picaridin.
AB  - Behavioral bioassays remain a standard tool in the discovery, development, and
      registration of arthropod repellents. Tick repellent bioassays are generally
      uncomplicated, but their results can be affected by basic variables (e.g.,
      dimensions of testing materials, substrate, timing, temperature) of the assay.
      Using lone star tick, Amblyomma americanum (L.), nymphs in climbing bioassays, we
      tested for the effects of substrate, solvent, and drying time on tick responses.
      In dose-response tests, the widely used repellents N,N-diethyl-3-methyl benzamide
      (deet) and 1-methyl-propyl-2-(hydroxyethyl)-1-piperidinecarboxylate (picaridin)
      were applied to filter paper strips and challenged by ticks at 10, 20, 30, 40,
      and 120 min after application. At 10-min drying time, repellency at the
      intermediate concentration 500 nmol repellent/cm2 filter paper was significantly
      lower for ethanol solutions of deet and picaridin (0 and 10% ticks repelled,
      respectively) than for solutions of deet and picaridin in acetone (96.7 and 76.7%
      ticks repelled, respectively). Repellency was greatest for both the acetone and
      ethanol solutions of deet and picaridin when challenged 120 min after
      application, and at shorter drying times at the highest concentration tested
      (2,000 nmol compound/ cm2). The repellency of picaridin relative to deet differed
      at some combinations of solvent and drying time but not others. In dose-response
      tests using different paper substrates and a drying time of 10 min, both ethanol
      and acetone solutions of deet differed in repellency, depending on both the paper
      substrate and the solvent. However, there were no differences in repellency
      between ethanol and acetone solutions of deet applied to nylon organdy in an in
      vitro and in an in vivo (fingertip) bioassay. When deet in solution with various
      proportions of ethanol:water was applied at 2,000 nmol deet/cm2 filter paper, the
      proportion of ticks repelled decreased as the proportion of water in the test
      solutions increased. Somewhat similar results were seen for solutions of deet in
      an acetone solvent. Water absorbed from the atmosphere may affect the efficacy of
      repellents in solution with anhydrous ethanol. Overall, results obtained from
      bioassays that differ in seemingly minor ways can be surprisingly different,
      diminishing the value of comparing studies that used similar, but not identical,
      methods. Nylon organdy or another similar thin cloth may be preferable to filter
      papers and copier paper for minimizing solvent-related differences. When a paper
      substrate is used, acetone may be the more suitable solvent if the solubility of
      the test compound and other factors allow.

PMID- 24897856
TI  - Susceptibility of cat fleas (Siphonaptera: Pulicidae) to fipronil and
      imidacloprid using adult and larval bioassays.
AB  - The monitoring of the susceptibility offleas to insecticides has typically been
      conducted by exposing adults on treated surfaces. Other methods such as topical
      applications of insecticides to adults and larval bioassays on treated rearing
      media have been developed. Unfortunately, baseline responses of susceptible
      strains of cat flea, Ctenocephalides felis (Bouche), except for imidacloprid,
      have not been determined for all on-animal therapies and new classes of chemistry
      now being used. However, the relationship between adult and larval bioassays of
      fleas has not been previously investigated. The adult and larval bioassays of
      fipronil and imidacloprid were compared for both field-collected isolates and
      laboratory strains. Adult topical bioassays of fipronil and imidacloprid to
      laboratory strains and field-collected isolates demonstrated that LD50s of
      fipronil and imidacloprid ranged from 0.11 to 0.40 nanograms per flea and 0.02 to
      0.18 nanograms per flea, respectively. Resistance ratios for fipronil and
      imidacloprid ranged from 0.11 to 2.21. Based on the larval bioassay published for
      imidacloprid, a larval bioassay was established for fipronil and reported in this
      article. The ranges of the LC50s of fipronil and imidacloprid in the larval
      rearing media were 0.07-0.16 and 0.11-0.21 ppm, respectively. Resistance ratios
      for adult and larval bioassays ranged from 0.11 to 2.2 and 0.58 to 1.75,
      respectively. Both adult and larval bioassays provided similar patterns for
      fipronil and imidacloprid. Although the adult bioassays permitted a more precise
      dosage applied, the larval bioassays allowed for testing isolates without the
      need to maintain on synthetic or natural hosts.

PMID- 24897857
TI  - Susceptibility to chlorpyrifos in pyrethroid-resistant populations of Aedes
      aegypti (Diptera: Culicidae) from Mexico.
AB  - Resistance to the organophosphate insecticide chlorpyrifos was evaluated in
      females from six strains of Aedes aegypti (L.) that expressed high levels of
      cross-resistance to eight pyrethroid insecticides. Relative to LC50 and LC90 at
      24 h of a susceptible New Orleans (NO) strain, three strains were highly
      resistant to chlorpyrifos (Coatzacoalcos, resistance ratio [RRLC90 = 11.97;
      Pozarica, RRLC90 = 12.98; and Cosoleacaque, RRLC50 = 13.94 and RRLC90 = 17.57),
      one strain was moderately resistant (Veracruz, RRLC90 = 5.92), and two strains
      were susceptible (Tantoyuca and Martinez de la Torre, RRLC50 and RRLC90 < 5) in
      bottle bioassays according to Centers for Disease Control and Prevention.
      Furthermore, high levels of alpha- or beta-esterase activity in the sample
      populations were correlated with resistance, suggesting that esterase activity
      may be a mechanism causing the development of organophosphate resistance in these
      populations. Overall, the populations in this study were less resistant to
      chlorpyrifos than to pyrethroids. Rotation of insecticides used in control
      activities is recommended to delay or minimize the occurrence of high levels of
      resistance to chlorpyrifos among local populations of Ae. aegypti. The diagnostic
      dose and diagnostic time for chlorpyrifos resistance monitoring was determined to
      be 85 microg per bottle and 30 min, respectively, using the susceptible NO
      strain.

PMID- 24897858
TI  - Toxicity of basil oil constituents and related compounds and the efficacy of
      spray formulations to Dermatophagoides farinae (Acari: Pyroglyphidae).
AB  - Pyroglyphid house dust mites are the most common cause of allergic symptoms in
      humans. An assessment was made of the toxicity of basil, Ocimum basilicum L,
      essential oil, 11 basil oil constituents, seven structurally related compounds,
      and another 22 previously known basil oil constituents to adult American house
      dust mites, Dermatophagoides farinae Hughes. The efficacy of four experimental
      spray formulations containing basil oil (1, 2, 3, and 4% sprays) was also
      assessed. Results were compared with those of two conventional acaricides benzyl
      benzoate and N,N-diethyl-3-methylbenzamide. The active principles of basil oil
      were determined to be citral, alpha-terpineol, and linalool. Citral (24 h LC50,
      1.13 microg/cm2) and menthol (1.69 microg/cm2) were the most toxic compounds,
      followed by methyl eugenol (5.78 microg/cm2). These compounds exhibited toxicity
      greater than benzyl benzoate (LC50, 8.41 microg/cm2) and N,N-diethyl-3
      methylbenzamide (37.67 microg/cm2). Potent toxicity was also observed with
      eugenol, menthone, spathulenol, alpha-terpineol, nerolidol, zerumbone, and nerol
      (LC50, 12.52-21.44 microg/cm2). Interestingly, the sesquiterpenoid alpha
      humulene, lacking only the carbonyl group present in zerumbone, was significantly
      less effective than zerumbone, indicating that the alpha,beta-unsaturated
      carbonyl group of zerumbone is a prerequisite component for toxicity. These
      compounds were consistently more toxic in closed versus open containers,
      indicating that their mode of delivery was largely a result of vapor action.
      Basil oil applied as 3 and 4% sprays provided 97 and 100% mortality against the
      mites, respectively, whereas permethrin (cis:trans, 25:75) 2.5 g/liter spray
      treatment resulted in 17% mortality. Our results indicate that practical dust
      mite control in indoor environments can be achieved by basil oil spray
      formulations (3 and 4% sprays) as potential contact-action fumigants.

PMID- 24897859
TI  - Establishment of Orientia tsutsugamushi Lc-1 (Rickettsiales: Rickettsiaceae)
      infection in ICR outbred mice (Rodentia: Muridae) by needle challenge.
AB  - Orientia tsutsugamushi is a pathogen transmitted by Leptotrombidium that causes
      scrub typhus. To develop an infection mouse model, a mite-derived isolate of O.
      tsutsugamushi was established from a laboratory-maintained colony of
      Leptotrombidium chiangraiensis (O. tsutsugamushi Lc-1). This Lc-1 isolate was
      initially presented to ICR (CD-1) mice by feeding an infected Lc chigger on the
      ear of a mouse. Once the Lc-1 was adapted to the ICR mice, quantitative real-time
      polymerase chain reaction was used to investigate O. tsutsugamushi genomic
      equivalent copies in tissues and sera. Furthermore, times to onset of the signs
      of infection are reported in this study. This study provides information useful
      for future research on this host-pathogen interaction and the associated vaccine
      efficacy trials.

PMID- 24897860
TI  - Aedes albopictus (Diptera: Culicidae) as a potential vector of endemic and exotic
      arboviruses in Australia.
AB  - In 2005, established populations of Aedes albopictus (Skuse) were discovered in
      the Torres Strait, the region that separates Papua New Guinea from northern
      Australia. This increased the potential for this species to be introduced to
      mainland Australia. Because it is an arbovirus vector elsewhere, we undertook
      laboratory-based infection and transmission experiments to determine the
      potential for Ae. albopictus from the Torres Strait to become infected with and
      transmit the four major Australian endemic arboviruses--Murray Valley
      encephalitis virus, West Nile virus Kunjin strain (WNV(KUN)), Ross River virus
      (RRV), and Barmah Forest virus--as well as the exotic Japanese encephalitis
      virus. Ae. albopictus is susceptible to infection with all viruses, with
      infection rates ranging between 8% for WNV(KUN) and 71% for RRV. Transmission
      rates of approximately 25% were observed for RRV and Barmah Forest virus, but
      these were < 17% for Murray Valley encephalitis virus, WNV(KUN), and Japanese
      encephalitis virus. Given its relative vector competence for alphaviruses, we
      also examined the replication kinetics and extrinsic incubation periods required
      for transmission of RRV and chikungunya virus. Despite lower body titers, more
      mosquitoes reared and maintained at 28 degrees C became infected with and
      transmitted the virus than those reared and maintained at 22 degrees C. The
      minimum time between Ae. albopictus consuming an infected bloodmeal and
      transmitting chikungunya virus was 2 d at 28 degrees C and 4 d at 22 degrees C,
      and for RRV, it was 4 d, irrespective of the temperature. Given its opportunistic
      feeding habits and aggressive biting behavior, the establishment of Ae.
      albopictus on the Australian mainland could have a considerable impact on
      alphavirus transmission.

PMID- 24897861
TI  - The effects of temperature and innate immunity on transmission of Campylobacter
      jejuni (Campylobacterales: Campylobacteraceae) between life stages of Musca
      domestica (Diptera: Muscidae).
AB  - The house fly (Musca domestica L.) is a well-established vector of human
      pathogens, including Campylobacter spp., which can cause infection of broiler
      chicken flocks, and through contaminated broiler meat can cause outbreaks of
      campylobacteriosis in humans. We investigated whether Campylobacter jejuni
      (Jones) could be transferred between life stages of M. domestica (larvae-pupae
      adults) and determined bacterial counts of C. jejuni at different time points
      after bacterial exposure. C. jejuni was transmitted from infected larvae to
      pupae, but not to the adult stage. Infected larvae maintained at 25 degrees C had
      mean bacterial numbers of 6.5 +/- 0.2 SE log10 (colony forming units [CFU]/g)
      that subsequently dropped to 3.6 +/- 0.3 SE log10 (CFU/g) 8 h after infection.
      Pupae originating from infected larvae contained mean bacterial numbers of 5.3 +/
      0.1 SE log10 (CFU/g), and these numbers dropped to 4.8 +/- 0.1 SE log10 (CFU/g)
      24 h after pupation. The decline in C. jejuni numbers during pupal development
      coincided with increased expression of antimicrobial peptides, including
      cecropin, diptericin, attacin, and defensin, in the larva-pupa transition stage
      and a later second peak in older pupae (4 or 48 h). Conversely, there was a
      reduced expression of the digestive enzyme, lysozyme, in pupae and adults
      compared with larvae.

PMID- 24897862
TI  - Molecular identification of bloodmeals from sand flies and mosquitoes collected
      in Israel.
AB  - In Israel, sand flies are the vectors of Leishmania Ross and mosquitoes are the
      vectors of West Nile Virus. In the Judean Desert and Tiberias, the sand fly
      Phlebotomus sergenti Parrot is the vector of Leishmania tropica (Wright) and the
      rock hyrax (Procavia capensis Pallas) is considered the main reservoir animal.
      The main vectors of West Nile Virus are Culex pipiens L. and Culex perexiguus
      Theobald. Bloodmeals of engorged field-caught female sand flies and mosquitoes
      are an important source for defining host preferences. Recent progress in DNA
      molecular techniques has enabled the accurate identification of blood sources
      within the arthropod gut. In this study, we applied molecular approach for
      species-specific identification based on polymerase chain reaction and nucleotide
      sequence analysis of polymorphic regions along two mitochondrial genes, 12S and
      16S rRNA. The research was carried out on 261 engorged female sand flies
      collected in the Judean Desert and Tiberias and 50 engorged female mosquitoes
      collected in Tel-Aviv and Arava. Species identification of bloodmeals was
      successful in 92% of the samples. Rock hyrax was the most abundant host in
      bloodmeals of P. sergenti, while human blood was found in only seven (3%)
      females. L. tropica DNA was detected in three P. sergenti females from Tiberias
      that contained rock hyrax blood. Avian sequences were detected in 67% (10 of 15)
      of the identified bloodmeals from Cx. perexiguus and in 10% (3 of 29) of the
      identified meals from Cx. pipiens. Human sequences were found in 14% of the
      identified bloodmeals from Cx. pipiens. The successful analysis of the majority
      of the bloodmeals performed on wild sand flies and mosquitoes suggests that
      bloodmeal identification can be applied as one of the routine procedures in
      vector surveillance programs.

PMID- 24897864
TI  - Prevalence of Borrelia burgdorferi and Anaplasma phagocytophilum in Ixodes
      scapularis (Acari: Ixodidae) nymphs collected in managed red pine forests in
      Wisconsin.
AB  - Changes in the structure of managed red pine forests in Wisconsin caused by
      interacting root- and stem-colonizing insects are associated with increased
      abundance of the blacklegged tick, Ixodes scapularis Say, in comparison with
      nonimpacted stands. However, the frequency and variability of the occurrence of
      tick-borne pathogens in this coniferous forest type across Wisconsin is unknown.
      Red pine forests were surveyed from 2009 to 2013 to determine the prevalence of
      Borrelia burgdorferi and Anaplasma phagocytophilum in questing I. scapularis
      nymphs. Polymerase chain reaction analysis revealed geographical differences in
      the nymphal infection prevalence (NIP) of these pathogens in red pine forests. In
      the Kettle Moraine State Forest (KMSF) in southeastern Wisconsin, NIP of B.
      burgdorferi across all years was 35% (range of 14.5-53.0%). At the Black River
      State Forest (BRSF) in western Wisconsin, NIP of B. burgdorferi across all years
      was 26% (range of 10.9-35.5%). Differences in NIP of B. burgdorferi between KMSF
      and BRSF were statistically significant for 2010 and 2011 and for all years
      combined (P < 0.05). NIP ofA. phagocytophilum (human agent) averaged 9% (range of
      4.6-15.8%) at KMSF and 3% (range of 0-6.4%) at BRSF, and was significantly
      different between the sites for all years combined (P < 0.05). Differences in
      coinfection of B. burgdorferi and A. phagocytophilum were not statistically
      significant between KMSF and BRSF, with an average of 3.4% (range of 1.7-10.5%)
      and 2.5% (range of 0-5.5%), respectively. In 2013, the density of infected nymphs
      in KMSF and BRSF was 14 and 30 per 1000m2, respectively, among the highest ever
      recorded for the state. Differences in the density of nymphs and NIP among sites
      were neither correlated with environmental factors nor time since tick
      colonization. These results document significant unexplained variation in tick
      borne pathogens between coniferous forests in Wisconsin that warrants further
      study.

PMID- 24897865
TI  - Environmental factors affecting early carcass attendance by four species of blow
      flies (Diptera: Calliphoridae) in Texas.
AB  - As the most common primary colonizer of carrion, adult blow flies (Diptera:
      Calliphoridae) play an important role in initiating arthropod-mediated breakdown
      of soft tissue; however, their timing is highly variable. This variability
      complicates the estimation of precolonization intervals or periods of insect
      activity by forensic entomologists. In this study, the size of the adult blow fly
      on swine carcasses was compared with various environmental conditions including
      time of day, temperature, wind speed, and light levels. Four trials were
      conducted: two in August and September 2008, one in January 2009, and one in
      February-March 2010. Of the measured variables, time of day was the only
      consistent factor explaining the population size of blow fly on a carcass,
      although precipitation and high winds affected winter-active Calliphora vicina
      Robineau-Desvoidy. Male flies were also collected, suggesting that carcasses may
      play additional roles in adult blow fly ecology beyond that of a simple
      oviposition site. For both sexes of flies, a strong diel pattern of behavior
      emerged, which could be useful in estimating precolonization intervals by
      considering the environmental conditions at a scene, and thus forensic
      entomologists may be better able to estimate the likelihood of adult activity at
      a carcass.

PMID- 24897863
TI  - Survey of Trypanosoma and Leishmania in wild and domestic animals in an Atlantic
      rainforest fragment and surroundings in the state of Espirito Santo, Brazil.
AB  - Trypanosoma and Leishmania infections affect wild and domestic animals and human
      populations. The growing process of deforestation and urbanization of Atlantic
      Rainforest areas has given rise to introduction of humans and domestic animals to
      the sylvatic cycles of Trypanosoma and Leishmania species. Serological,
      parasitological, and molecular surveys among wild and domestic animals in the
      Corrego do Veado Biological Reserve, which is an Atlantic Rainforest fragment in
      the state of Espirito Santo, southeastern Brazil, were evaluated. In total, 154
      wild animals of 25 species and 67 domestic animals (47 dogs and 20 horses) were
      sampled. All the domestic animals were serologically negative for anti-Leishmania
      infantum chagasi antibodies and negative in parasitological approaches. Only the
      Order Chiroptera presented positive blood cultures and cryopreserved isolates.
      The phylogenetic trees based on SSU rDNA and gGAPDH genes confirmed the
      occurrence of Trypanosoma dionisii and provided the first record of Trypanosoma
      cruzi marinkellei in southeastern Brazil. The studies conducted in Atlantic
      Rainforest remaining trees provide the knowledge of parasite diversity or detect
      parasites that can accelerate the loss of hosts diversity.

PMID- 24897866
TI  - Suppression of Amblyomma americanum (Ixodida: Ixodidae) for short-term field
      operations utilizing cypermethrin and lambda-cyhalothrin.
AB  - Tick-borne diseases pose significant risks to U.S. military personnel who conduct
      operations, both domestic and abroad. To determine the feasibility of protecting
      personnel from tick vectors during short-term field deployments, acaricides
      cypermethrin (Demon WP, Syngenta, Greensboro, NC) and lambda-cyhalothrin
      (Surrender Pestabs, CSI, Pasadena, TX) were applied to plots within two separate
      field sites on Camp Blanding Joint Training Center in Starke, FL, from May to
      June 2011. We analyzed their effectiveness in reducing tick counts for 6 wk after
      application. In total, 8,193 ticks were identified and counted, of which > 99%
      were a mix of nymphs and adult-stage Amblyomma americanum (L.). Our results
      indicate that both cypermethrin and lambda-cyhalothrin were effective in
      significantly reducing tick numbers and preventing entry into treated plots for 6
      wk after application. Thus, these two acaracides can be used to effectively
      suppress tick populations and provide residual protection in small geographic
      areas of recreation or public health significance.

PMID- 24897867
TI  - A fresh liver agar substrate for rearing small numbers of forensically important
      blow flies (Diptera: Calliphoridae).
AB  - Forensically important calliphorids can be reared on a mixture of beef liver and
      agar. Small pieces of meat, especially fresh or frozen beef liver, will desiccate
      in 2-6 h, but this simple-to-make feeding substrate remains moist for at least 12
      h at 25 and 30 degrees C without desiccation, even in small (5 g) amounts. We
      determined the survivorship of small numbers of Chrysomya megacephala (F.) (first
      instar larvae to adult eclosion) raised on 5 g of liver agar and fresh beef
      liver. We found that all larvae raised on 5 g of liver died due to desiccation,
      but survivorship on 5 g of liver agar was equivalent to that on larger (50 g)
      pieces of either liver agar or beef liver.

PMID- 24897854
TI  - Genetic variability and geographical diversity of the main Chagas' disease vector
      Panstrongylus megistus (Hemiptera: Triatominae) in Brazil based on ribosomal DNA
      intergenic sequences.
AB  - Studies were made on the ribosomal DNA intergenic region, comprising complete
      internal transcribed spacer (ITS)-1, 5.8S, and ITS-2 sequences, of populations of
      the triatomine Panstrongylus megistus, the most important vector of Chagas'
      disease in Brazil since Triatoma infestans eradication. Specimens were from 26
      localities of Rio Grande do Sul, Santa Catarina, Parana, Sao Paulo, Minas Gerais,
      Bahia, and Sergipe states. In total, 21 ITS-1 and 12 ITS-2 haplotypes were found.
      Nucleotide differences were higher in ITS-1 (3.00%) than in ITS-2 (1.33%). The
      intergenic region was 1,513-1,522-bp-long (mean 1,516.9 bp), providing 26
      combined haplotypes. The combination of microsatellites found in both ITSs may be
      of applied usefulness, to assess interpopulation specimen exchange and potential
      recolonizations after vector elimination by control implementation. Network
      results suggest that Sao Paulo may be considered one of the spreading centers of
      this species. Molecular clock datation suggests that P. megistus populations are
      diversifying at least since 4.54 million years ago, with diversification still
      ongoing today by geographical isolation of populations. Evidence is provided
      about the relationship of genetic diversity with geographical spread that
      characterizes a major vector and explains its ability to colonize distant areas
      and different ecotopes, including human habitats, and consequently its importance
      in Chagas' disease epidemiology.

PMID- 24897868
TI  - Human wound colonization by Lucilia eximia and Chrysomya rufifacies (Diptera:
      Calliphoridae): myiasis, perimortem, or postmortem colonization?
AB  - The infestation of human or animal tissues by fly larvae has been given
      distinctive terminology depending on the timing and location of colonization.
      Wounds and orifices colonized by Diptera in a living human or animal are
      typically referred to as myiasis. When the colonization occurs after death, it is
      referred to as postmortem colonization and can be used to estimate the minimum
      postmortem interval. What happens when the human, as in the case presented here,
      has a necrotic limb while the human remains alive, at least for a short period of
      time? The case presented here documents perimortem wound colonization by Lucilia
      eximia (Wiedemann) and Chrysomya rufifacies (Macquart) and the considerations for
      approximating development temperatures and estimating the time of colonization
      (TOC). This represents the first record of L. eximia in human myiasis in the
      United States and the first record of the co-occurrence of L. eximia and C.
      rufifacies in human myiasis in the United States. The TOC was estimated using
      both ambient and body temperature. Insect colonization before death complicates
      the estimation of TOC and minimum postmortem interval and illustrates the problem
      of temperature approximation in forensic entomology casework.

PMID- 24897869
TI  - Nontarget effects of aerial mosquito adulticiding with water-based unsynergized
      pyrethroids on honey bees and other beneficial insects in an agricultural
      ecosystem of north Greece.
AB  - We assessed the nontarget effects of ultra-low-volume (ULV) aerial adulticiding
      with two new water-based, unsynergized pyrethroid formulations, Aqua-K-Othrine
      (FFAST antievaporant technology, 2% deltamethrin) and Pesguard S102 (10% d
      phenothrin). A helicopter with GPS navigation technology was used. One
      application rate was tested per formulation that corresponded to 1.00 g (AI)/ha
      of deltamethrin and 7.50 g (AI)/ha of d-phenothrin. Three beneficial nontarget
      organisms were used: honey bees (domesticated hives), family Apidae (Apis
      mellifera L.); mealybug destroyers, family Coccinellidae (Cryptolaemus
      montrouzieri Mulsant); and green lacewings, family Chrysopidae (Chrysoperla
      carnea (Stephens)). No significant nontarget mortalities were observed. No bees
      exhibited signs of sublethal exposure to insecticides. Beehives exposed to the
      insecticidal applications remained healthy and productive, performed as well as
      the control hives and increased in weight (25-30%), in adult bee population (14
      18%), and in brood population (15-19%).

PMID- 24897870
TI  - The path to expertise in youth sport: using a retrospective interview in three
      different competitive contexts.
AB  - The goal of this study was to identify contextual factors in the path to
      excellence in youth sport. 48 male athletes under 17 years of age (M = 15.7 yr.,
      SD = 1.0) from a soccer academy (n = 20), a volleyball club (n = 14), and an
      elite volleyball center (n = 14) participated in the study. A standardized,
      retrospective interview was administered. Demographic information, training
      loads, and incidence of injuries were also collected. Male soccer players had
      more years of practice in sport than their male volleyball peers, but elite male
      volleyball players practiced more hours per week than the other athletes. The
      perception of intensity of training, physical effort, and concentration in male
      soccer players was higher than in male volleyball players. The high demands of
      expertise in professional soccer leads young athletes to begin training at early
      ages. The results showed that the environment specificity shapes the way young
      male athletes perceive their participation and commitment in sport.

PMID- 24897871
TI  - Effect of treadmill versus overground running on the structure of variability of
      stride timing.
AB  - Gait timing dynamics of treadmill and overground running were compared. Nine
      trained runners ran treadmill and track trials at 80, 100, and 120% of preferred
      pace for 8 min. each. Stride time series were generated for each trial. To each
      series, detrended fluctuation analysis (DFA), power spectral density (PSD), and
      multiscale entropy (MSE) analysis were applied to infer the regime of control
      along the randomness-regularity axis. Compared to overground running, treadmill
      running exhibited a higher DFA and PSD scaling exponent, as well as lower entropy
      at non-preferred speeds. This indicates a more ordered control for treadmill
      running, especially at non-preferred speeds. The results suggest that the
      treadmill itself brings about greater constraints and requires increased
      voluntary control. Thus, the quantification of treadmill running gait dynamics
      does not necessarily reflect movement in overground settings.

PMID- 24897872
TI  - Performance indicators analysis at Brazilian and Italian women's volleyball
      leagues according to game location, game outcome, and set number.
AB  - This study was done to investigate the advantage of playing at home in elite
      women's volleyball leagues and the influence of performance indicators in the
      game score according to set number. The sample consisted of 240 games of the
      Brazilian Volleyball League (n = 132 games) and the Italian Volleyball League (n
      = 108 games) from the 2011-2012 season. The relationship of performance
      indicators (including serve, attack, block, and opponents' errors) with the game
      outcome (win or lose) was assessed. The results showed that there was a home
      advantage effect in women's volleyball leagues, with a higher prevalence of
      victory for the home teams in Brazilian and Italian leagues (58 and 56%,
      respectively). When related to the performance indicators and among the aspects
      that were most highly correlated with victory, the attack was the technical
      indicator that explained most of the results of volleyball games.

PMID- 24897873
TI  - Adolescents' physical activities and peer norms: the mediating role of self
      efficacy.
AB  - The purpose of the present study was to examine the relations among adolescents'
      self-efficacy and social norms, and physical activity and whether self-efficacy
      mediated the relationship between social norms and physical activity. 400 junior
      high school students (202 boys, 198 girls, 2 not identified; M age = 15.3yr., SD
      = 0.6) completed a demographic questionnaire, the International Physical Activity
      Questionnaire (IPAQ), the Perceived Self-Efficacy in Physical Activity Scale, and
      the Physical Activity Social Norms Scale. Regression analyses indicated that both
      self-efficacy and social norms predicted physical activity. Self-efficacy fully
      mediated the relationship between peer norms and physical activity for boys but
      partially mediated the relationship for girls. An application of the results may
      be to foster self-efficacy and peer norms as a motivational strategy for
      supporting increased physical activity.

PMID- 24897874
TI  - Trait anxiety and goal difficulty on learning to climb the Bachman ladder.
AB  - This study examined the effects of trait anxiety and goal setting on learning of
      the Bachman ladder. It was hypothesized that easy goals would increase learning
      for individuals with high trait anxiety while hard goals would increase learning
      for individuals with low trait anxiety. 80 high school students (40 boys, 40
      girls; M age = 15 yr., SD = 1.0) filled out the Brazilian State-Trait Anxiety
      Inventory (STAI) for trait anxiety. The experiment was divided into four phases:
      acquisition, immediate transfer (after 5 min.), delayed transfer, and retention
      (after 24 hr.). On the transfer phases, the participants started climbing the
      ladder with the foot opposite of that used in acquisition. Participants were
      assigned to one of four experimental groups combining high and low anxiety traits
      and hard and easy goals. Variances were analyzed with repeated measurements on
      the last factor of all phases. The results showed the performance increased
      during the acquisition phase and no effects were observed in any phases.

PMID- 24897875
TI  - Learning of a golf putting task with varying contextual interference levels
      induced by feedback schedule in novices and experts.
AB  - Switching between tasks during practice can affect motor learning. This study
      tested whether switching feedback content has any effects on learning to perform
      golf putts without full visibility. 60 participants (44 men, 16 women; M age =
      26.3 yr., SD = 6.6) practiced golf putts without seeing the ball movement. 30 of
      the participants were golfers with moderate expertise, and 30 were novices. They
      received feedback regarding their putts, either on the angle or on the distance
      in one of three feedback schedules: blocked, serial-blocked, or serial.
      Independent of the expertise level, learning was not affected by the feedback
      schedule. The strong linkage between the two components--direction and distance-
      may have prevented a sufficient level of contextual interference.

PMID- 24897876
TI  - Bilateral transfer for learning to control timing but not for learning to control
      fine force.
AB  - This study examined the characteristics of bilateral transfer of learning to
      control timing and fine force from a dominant limb to a nondominant limb. 20
      right-handed college students (12 women, 8 men; M age = 21.5 yr., SD = 2.3)
      learned a sequential task consisting of timing and force control. Each
      participant completed a pre-test of the task with both hands and then performed
      100 practice trials with the dominant hand. A post-test was conducted 1 hr.
      later. The results showed that after training, participants learned to control
      the timing and force. Nevertheless, only the time-control learning was
      transferred to the untrained hand, whereas the force-control learning did not
      transfer to the untrained hand.

PMID- 24897877
TI  - Word and pseudoword superiority effects in a shallow orthography language: the
      role of hemispheric lateralization.
AB  - The word superiority effect (WSE) has made it possible to demonstrate the
      automatic activation of lexical-orthographic entries in reading. The observation
      of this effect is important since it led to experimental support of the main
      cognitive reading models. These models were mostly developed on English data,
      hence the verification in different orthography systems is relevant. The present
      study tested WSE in Italian, a language in which this effect was predicted to be
      less constant given the highly consistent correspondence between orthography and
      phonology. Moreover, the presentation of the items in a lateralized visual field
      condition allowed testing of assumptions about the roles of the right and left
      hemispheres in written word recognition and, in particular, on the hemispheric
      lateralization of lexical processing. Two experiments were conducted with
      undergraduate students who had to recognize a target letter within a word,
      pseudoword, or nonword. In Experiment 1, prime and probe letters were in the same
      letter case, while in Experiment 2 they were in different letter cases. Error
      rates and reaction times were analyzed with mixed models. The results showed a
      superiority of pseudowords (pseudoword superiority effect; PSE) over illegal
      strings with no evidence of a clear superiority of words over pseudowords for
      both left and right visual field presentations. This suggests that in Italian,
      the sub-lexical route could play a major role in reading and that this route
      relies on a visual-perceptual orthographic coding concerning familiarity of
      letter combinations, which is also available to the right hemisphere.

PMID- 24897878
TI  - Cognitive and emotional reactions to questions in the Comparison Question Test.
AB  - The effect of situational factors on perceptions of items on the polygraph
      Comparison Question Test (CQT) was assessed. In an initial experiment, 86
      students (30 men, 56 women; M age = 20.3 yr., SD = 4.0) imagined one of eight
      scenarios that varied by guilt or innocence, the commission of a real crime or
      mock crime, and interrogation by a police officer or a professor. They then rated
      generic CQT questions for importance and emotional concern. All participants
      rated crime-relevant questions as being more important than past-crime comparison
      questions. "Guilty" participants also rated these questions as being more
      emotionally concerning, but "innocent" participants showed no differences in
      their ratings of concern for the two question types. Interrogator or crime type
      did not affect the general pattern of responding. A second experiment involving
      80 students (21 men, 58 women, 1 non-specified; M age = 22.5 yr., SD = 7.3)
      replaced the generic CQT questions with content-specific questions developed by
      the participant. Those imagining guilt showed no differencesin their ratings of
      relevant and comparison questions, whereas those imagining innocence rated
      comparison questions as more concerning. Again, interrogator type and crime type
      had little effect on results. Overall these findings indicated distinctions in
      cognitive and emotional appraisal for CQT questions, with the nature of emotional
      concern dependent on guilt/innocence status and the personal relevance of
      comparison questions. Evidence suggests that the CQT is robust to other
      situational factors, such as crime type and interrogator type.

PMID- 24897879
TI  - Predicting agility performance with other performance variables in pubescent
      boys: a multiple-regression approach.
AB  - The goal was to investigate the influence of balance, jumping power, reactive
      strength, speed, and morphological variables on five different agility
      performances in early pubescent boys (N = 71). The predictors included body
      height and mass, countermovement and broad jumps, overall stability index, 5 m
      sprint, and bilateral side jumps test of reactive strength. Forward stepwise
      regressions calculated on 36 randomly selected participants explained 47% of the
      variance in performance of the forward-backward running test, 50% of the 180
      degrees turn test, 55% of the 20 yd. shuttle test, 62% of the T-shaped course
      test, and 44% of the zig-zag test, with the bilateral side jumps as the single
      best predictor. Regression models were cross-validated using the second half of
      the sample (n = 35). Correlation between predicted and achieved scores did not
      provide statistically significant validation statistics for the continuous
      movement zig-zag test. Further study is needed to assess other predictors of
      agility in early pubescent boys.

PMID- 24897880
TI  - Bandwidth knowledge of results on the learning of the saloon dart throwing task.
AB  - The effects of two different bandwidths of information of Knowledge of Results
      (KR) were investigated. 54 university students participated. The experiment
      consisted of an acquisition phase with practice of throwing a saloon dart as
      accurately as possible at a target lying on the floor 2.5 meters away until a
      specific area of the target was hit three trials in a row. Narrow bandwidth and
      Wide bandwidth groups received KR when performance was outside the bandwidth. A
      Control group received KR after every trial. A transfer test was run 10 min.
      later with 10 more trials and the target 3.0 m away, with no KR. Analyses showed
      that narrow KR bandwidth was associated with better learning of real world tasks.

PMID- 24897881
TI  - Perception threshold of locomotor symmetry while walking on a split-belt
      treadmill in healthy elderly individuals.
AB  - Some hemiparetic patients walk asymmetrically. To better understand the
      mechanisms of this deficiency, the perception of locomotor symmetry was
      investigated in healthy elderly individuals. 16 participants (6 women, 10 men; M
      age = 70.9 yr., SD = 4.1) walked on a split-belt treadmill either at a self
      selected or imposed gait speed. The speed of the two belts was initially similar
      (or different) and then gradually differed (or matched), so participants had to
      detect the point of perceived asymmetry (or symmetry). The results revealed that
      thresholds occurred when the belt speed ratios were .88 and .85. Initial gait
      speed did not affect the threshold. The parameter that correlated the most with
      belt speed asymmetry was stance time of the parameters measured. Future studies
      will investigate whether stroke affects gait symmetry judgments.

PMID- 24897882
TI  - Effects of repetitive transcranial magnetic stimulation on the somatosensory
      cortex during prism adaptation.
AB  - Although the behavioral characteristics and the neural correlates of prism
      adaptation processes have been studied extensively, the underlying mechanism is
      yet to be investigated. Recently, somatosensory suppression was heralded as a
      mechanism for the sensory re-alignment process accompanying the adaptation.
      Somatosensory suppression should facilitate the re-alignment process in the
      proprioceptive system. The shift in the proprioceptive system takes place mostly
      during a concurrent visual feedback (CVF) condition; during a terminal visual
      feedback (TVF) condition, the visual system experiences significant adaptation
      (visual shift), so somatosensory suppression should have minimal functional
      consequences under TVF. To test this hypothesis, a repetitive transcranial
      magnetic stimulation (rTMS) was applied to the primary somatosensory cortex as an
      artificial somatosensory suppression right after the reaching initiation in CVF
      and TVF conditions, and changes in adaptation were observed. Because
      somatosensory suppression is already in effect during CVF, rTMS would cause no
      significant changes. During TVF with rTMS, however, significantly different
      patterns of adaptation could be expected when compared to a sham rTMS condition.
      Young adults (N = 12) participated in 4 sessions (CVF/ TVF, real/sham rTMS);
      visual proprioceptive, and total shifts were measured. Movement time and
      curvature of the reaching movement were measured during the adaptation phase.
      Results showed that while the total shift was unchanged, the proprioceptive shift
      increased and the visual shift decreased in the TVF condition when rTMS was
      delivered. However, the total, proprioceptive, and visual shifts were not
      influenced by rTMS in the CVF condition. Suppression of proprioception induced by
      the rTMS could be one of the requisites for successful proprioceptive shift
      during prism adaptation.

PMID- 24897883
TI  - RPE-derived work rates can be accurately produced without external feedback or
      reference to the RPE Scale.
AB  - Ratings of perceived exertion (RPE) are used to prescribe exercise intensity.
      This study assessed whether the accurate production of exercise intensity is
      affected when the rater cannot see the RPE scale. After completing a graded
      exercise test, 15 active, male participants (M age = 34, SD = 6.7 yr.; M mass =
      73.9, SD = 14.8kg, M height = 1.74, SD = 0.08m) completed 3 x 4 min. cycling
      trials at four randomised RPE-based intensities (RPEs 11, 13, 15, and 17).
      Participants were allocated to a Full feedback group or a No feedback group (RPEs
      not in view). On the third trial, No feedback conditions were imposed on the Full
      feedback group. No statistically significant differences between groups' mean
      work rates were observed. Changing from Full feedback to No feedback conditions
      led to a significant overestimation between the trials for power output at RPE
      11. Intra-class correlations were significant at RPEs 11, 13, and 17 between all
      trials for both conditions. Provided adequate familiarisation, active
      participants can accurately produce RPE derived work rates, even when RPE is not
      in view.

PMID- 24897884
TI  - The spiral aftereffect technique (SAT) can differentiate between depressive and
      somatoform disorder patients.
AB  - This study examined how differences in visuo-perceptual patterns are related to
      psychopathology. Fifty-six patients (37 women, 19 men; M age = 43.8 yr., SD =
      13.4) with a main diagnosis of unipolar depression and 42 patients (22 women, 20
      men; M age = 42.0 yr., SD = 11.1) with a main diagnosis of somatoform disorder
      were compared. The duration and trend of a visual motion aftereffect were
      measured with the Spiral Aftereffect Technique (SAT). The results indicated that
      successively increasing aftereffect durations characterized the depressive
      patients, whereas patterns of very short or short final aftereffect preceded by
      successively decreasing aftereffect durations characterized the patients with a
      somatoform disorder. The SAT is thus a valuable tool for linking objectively
      measured perceptual-personality characteristics with some mental disorders.

PMID- 24897885
TI  - Co-witness auditory memory conformity following discussion: a misinformation
      paradigm.
AB  - Twenty-four Japanese undergraduate pairs (12 male and 12 female pairs)
      participated as witnesses to a simulated criminal event. Although the witness
      pairs watched the same video together, through wireless headphones they
      experienced two different auditory versions with four differing items without
      being aware of the discrepancies. After the presentation, the witnesses were led
      to discuss six items, including two critical ones they had heard differently and
      another four they had heard in common. Witness memory performance was assessed
      individually with multiple-choice questionnaires in three sessions: before the
      discussion, after the discussion, and 1 week later. The results showed that
      participants tended to conform to their co-witness more often on the discussed
      items than on the not-discussed items. Source monitoring analyses on the four
      critical items revealed that even those participants who conformed were mostly
      cognizant of the source of their information just after the discussion, but they
      were prone to source-monitoring errors a week later.

PMID- 24897886
TI  - Brazilian adolescents' body weight misperception and the Human Development Index
      of the cities where they live.
AB  - This study investigated the relationship between adolescents' body weight
      misperception and the Human Development Index (HDI) of the cities in which they
      live in Brazil. Data from a large national survey that included 60,973 boys and
      girls between 13 and 15 yr. (M = 14.2, SD = 1.1; 47.5% boys, 52.5% girls) were
      analyzed. Regression analyses were adjusted for potential confounding factors
      such as population density, income inequality, nutritional status (BMI), and
      mothers' education. In both sexes, the relationship between perceived underweight
      showed an inverse relationship with HDI. The highest prevalences of participants
      who perceived themselves as overweight for girls were found in cities with high
      HDI.

PMID- 24897887
TI  - Test-retest reliability of the Bod Pod: the effect of multiple assessments.
AB  - The Bod Pod uses air-displacement plethysmography to estimate body fat percentage
      (BF%). This study was designed to assess the test-retest reliability of the Bod
      Pod. The study included 283 women (M age = 41.0 yr., SD = 3.0). Each participant
      was tested at least twice in the Bod Pod. Results showed no significant mean
      difference between the test and the retest. The intraclass correlation
      coefficient (ICC) was .991. However, the absolute value of the initial trial
      differences (absolute mean difference) was .96 (SD = .90). A third assessment of
      BF% was taken when the initial trial difference was greater than 1 percentage
      point, and the two closest values were compared. This strategy resulted in a
      significant decrease in the absolute mean difference, from .96 to .55 percentage
      point, and ICC increased to .998. The Bod Pod appears to measure body fat
      percentage reliably; however, findings suggest that multiple trials may be
      necessary to detect small treatment effects.

PMID- 24897888
TI  - Prevalence and correlates of insomnia and excessive sleepiness in adults with
      obstructive sleep apnea symptoms.
AB  - This study investigated the prevalence and correlates of insomnia and excessive
      sleepiness in adults presenting symptoms of obstructive sleep apnea (OSA) in the
      general population. Randomly selected participants (N = 1,502; 50.7% men, 49.3%
      women), ages 40 to 70 yr. (M = 53.6, SD = 8.5) were interviewed over the
      telephone. Insomnia and excessive sleepiness (hypersomnia) were assessed with the
      Bergen Insomnia Scale and the Epworth Sleepiness Scale, respectively. OSA
      symptoms were identified by self- or spouse reports on snoring, breathing
      cessations during sleep, and being tired or sleepy. The prevalence of OSA was
      6.2%. Among these participants with OSA, 57.6% reported insomnia and 30.1%
      reported excessive sleepiness. Furthermore, OSA symptoms were associated with
      self-reported obesity, hypertension, diabetes, and depression, but only in
      participants with comorbid insomnia or excessive sleepiness.

PMID- 24897889
TI  - Representation of haptic objects during mental rotation in congenital blindness.
AB  - The representation of haptic objects by three groups of participants (sighted,
      blindfolded, and congenitally blind) was studied in a mental-rotation task. Three
      models were tested. The participants explored a standard object continuously with
      the left hand and tried to find the mirror object among two alternatives explored
      sequentially with the right hand. Sighted participants were tested in the visual
      version of the task. The accuracy of judgments was very high (> 95%) for all
      groups, and the blind group had the highest identification times. Correlation
      analyses were performed between (both single-trial and average) identification
      times and angular differences. The identification times of the sighted and
      blindfolded groups increased as linear functions of the angular difference
      between the mirror and the standard stimuli, supporting the classical model. The
      identification times of the blind group changed non-monotonically and were
      consistent with an antiparallel image (180 degrees rotation superimposed) in the
      mental representation. The dual code model did not fit the data well for any
      participant group. The performance differences between the blindfolded and blind
      groups may be attributed to a modified mapping function from the object
      properties-processing sub-system to the visual buffer, which was conjectured to
      be available also to the blind group while processing haptic objects.

PMID- 24897890
TI  - Comparing technical proficiency of elite table tennis players with intellectual
      disability: simulation testing versus game play.
AB  - Technical skill proficiency among elite table tennis players with intellectual
      disabilities (ID) was investigated in this study using two approaches: an off
      court simulation testing protocol and an on-court, standardized observational
      framework during game play. Participants included 24 players with ID (M age = 25
      yr., SD = 6; M IQ = 61, SD = 9), the top 16 performers, 13 men and 11 women, at
      the International Federation for sport for para-athletes with an intellectual
      disability (Inas) World Championships. Self-reported table tennis training
      experience of the players was 13 +/- 5 yr. In the Simulation Testing condition,
      players were instructed to play five sets of basic and five sets of advanced
      skills, which were subsequently assessed by experts using a standardized and
      validated observational protocol. The same protocol was used to assess the same
      skills during Game Play. Ratings of overall technical proficiency were not
      significantly different between Simulation Testing and Game Play conditions.
      There was a strong positive correlation between technical proficiency measured
      during Game Play vs Simulation Testing for the variables flick, topspin forehand,
      and topspin backhand. No correlations were found for the variables contra, block,
      and push. Insight into this relationship is important for future development of
      classification systems for ID athletes in the Paralympic Games, because comparing
      competition observation with the athlete's potential shown during the
      classification session is essential information for classifiers to confirm the
      athlete's competition class.

PMID- 24897891
TI  - Labial vibrotactile somatosensory perception: a pilot study in healthy aging
      versus young adult participants.
AB  - The purpose of this pilot study was to begin characterizing changes in labial
      vibrotactile somatosensation in healthy older adults as a foundational step in
      determining how changes in orofacial sensation can affect functional behaviors,
      such as speech and feeding. Labial vibrotactile perception capacity of healthy
      older adults (n = 15) was compared to a cohort of healthy young adults (n = 5).
      Vibrotactile inputs were delivered to the glabrous surface of the left lower lip
      at 5, 10, 50, and 150 Hz. A modified von Bekesy (staircase) method was used to
      identify participants' thresholds and response standard deviations for each test
      frequency. Consistent with findings in other body regions, a decrease in labial
      vibrotactile detection sensitivity was expected in healthy older adults. The
      threshold values for the 5 and 10 Hz test frequencies were higher in the older
      group and the differences in response standard deviations at these frequencies
      were statistically significant. This pilot study identified changes in labial
      perception among healthy older adults.

PMID- 24897892
TI  - Persian adaptation of Foreign Language Reading Anxiety Scale: a psychometric
      analysis.
AB  - The validity and psychometric properties of a new Persian adaptation of the
      Foreign Language Reading Anxiety Scale were investigated. The scale was
      translated into Persian and administered to 160 undergraduate students (131
      women, 29 men; M age = 23.4 yr., SD = 4.3). Rasch model analysis on the scale's
      original 20 items revealed that the data do not fit the partial credit model.
      Principal components analysis identified three factors: one related to feelings
      of anxiety about reading, the second reflected the reverse-worded items, and the
      third related to general ideas about reading in a foreign language. In a re
      analysis, the 12 items that loaded on the first factor showed a good fit with the
      partial credit model.

PMID- 24897893
TI  - Evaluations of the psychometric properties of the Recovery-Stress Questionnaire
      for Athletes among a sample of young French table tennis players.
AB  - This study used confirmatory factor analyses (CFAs) among a sample of young
      French table tennis players to test: (a) original 19-factor structure, (b) 14
      factor structure recently suggested in literature, and (c) hierarchical factor
      structure of the Recovery-Stress Questionnaire for Athletes (RESTQ-Sport). 148
      table tennis players completed the RESTQ-Sport and other self-report
      questionnaires between one to five occasions with a delay of 1 mo. between each
      completion. Results of CFAs showed: (a) evidence for relative superiority of the
      original model in comparison to an alternative model recently proposed in
      literature, (b) a good fit of the data for the 67-item 17-factor model of the
      RESTQ-Sport, and (c) an acceptable fit of the data for the hierarchical model of
      the RESTQ-Sport. Correlations between RESTQ-Sport subscales and burnout and
      motivation subscales also provided evidence for criterion-related validity of the
      RESTQ-Sport. This study provided support for reliability and validity of the
      RESTQ-Sport.

PMID- 24897895
TI  - Construct and incremental validity of the Rotter Incomplete Sentences Blank in
      adult psychiatric outpatients.
AB  - The expression of positive vs negative attitudes in response to the 40 stems of
      the Rotter Incomplete Sentences Blank (RISB) can be scored and summed to an
      Overall Adjustment Score (OAS). By extending the validation of the OAS to adult
      psychiatric outpatients, this study demonstrates for the first time the
      incremental validity of a personality test over a simple self-rating. The RISB
      and six tests of adjustment were administered to 41 recent admissions to
      psychotherapy in two rural clinics. The tests of adjustment were selected to
      cover the two domains of symptoms vs function and the three methods of interview
      schedule vs objective inventory vs therapist ratings. Their scores were combined
      into an adjustment composite. The OAS related strongly to the composite in
      univariate regression, and moderately in hierarchical regression after covarying
      demographics, intelligence, social desirability, and self-ratings of adjustment.
      Construct validity was good, and incremental validity at least fair.

PMID- 24897894
TI  - Relation between emotion regulation and mental health: a meta-analysis review.
AB  - This meta-analysis examined the relationship between emotion regulation
      strategies (cognitive reappraisal, expressive suppression) and mental health
      (measured by life-satisfaction, positive affect, depression, anxiety, and
      negative affect). 48 studies, which included 51 independent samples, 157 effect
      sizes, and 21,150 participants, met the inclusion criteria. The results showed
      that cognitive reappraisal was correlated significantly and positively with
      positive indicators of mental health (r = .26) and negatively with negative
      indicators of mental health (r = -.20). Expressive suppression was correlated
      negatively with positive indicators of mental health (r = -.12), and positively
      with negative indicators of mental health (r =.15). Expressive suppression was
      correlated positively with positive indicators of mental health within the
      category of samples with Western cultural values (r = -.11) but not the category
      with Eastern cultural values. Moreover, the correlation of expressive suppression
      and negative indicators of mental health was stronger in the Western cultural
      values category (r = .19) than in the Eastern cultural values category (r = .06).
      Therefore, it is necessary for follow-up studies about emotion regulation and
      mental health to consider some moderator variable like the culture.

PMID- 24897896
TI  - Work-related psychosocial stress as a risk factor for asthma, allergy, and
      respiratory infections in the Swedish workforce.
AB  - This study examined the association between work-related psychosocial stress and
      asthma, atopy, and respiratory infections. 532 randomly selected occupationally
      active people (272 men, 260 women; M age = 41 yr., SD = 13) in Sweden
      participated. Information on history of asthma, atopy, and respiratory infections
      was collected by a postal self-report questionnaire. Work stress was assessed
      based on the demands-control-support model. Current asthma and respiratory
      infections were associated with work-related psychosocial stress. When stratified
      for sex, these associations were only found in men. Associations between low
      control, low support, and current asthma were found among young participants (<
      40 years), whereas among older participants (> 40 years) low supervisor support
      was associated with frequent respiratory infections.

PMID- 24897897
TI  - Factors associated with coping mechanisms among Egyptian patients with end stage
      renal disease and on haemodialysis.
AB  - This study intends to identify factors that influence coping with physical and
      emotional impacts of haemodialysis on patients in Egypt. A questionnaire was
      administrated to a random sample of 162 participants, 87 men and 75 women, who
      had received outpatient treatment in health care clinics in seven Egyptian
      cities. A regression model was used with four independent variables (view of
      medical treatment, effect of pain, adjustment to treatment, and satisfaction with
      life) to explain variance in satisfaction with self and coping. Results show
      about half the variance in the patients' ability to cope and express satisfaction
      with the self was explained by the independent variables (R2 = -.55, R2 = .45).
      Implications contributing to adjustment and coping are presented, showing the
      need to advance medical service and enhance patients' ability to develop
      effective strategies.

PMID- 24897898
TI  - Sex differences and the interaction of age and sleep issues in neuropsychological
      testing performance across the lifespan in an ADD/ADHD sample from the years 1989
      to 2009.
AB  - Chart review of population (9 to 80 years) neuropsychological test battery for
      ADHD diagnosis, questionnaires with multiple responders were evaluated in
      outpatient setting from 1989-2009. The focus was gender differences across age,
      diagnostic group (ADHD-Inattentive/ADHD plus), neuropsychological test
      performance, and reported sleep symptoms over the lifespan. Individuals were
      assigned to ADHD-I group or ADHD plus group (based upon secondary diagnosis of
      sleep, behavioral, emotional disturbance); ADHD not primary was excluded (brain
      insult, psychosis). Among these were 1,828 children (ages 9 to 14), adolescents
      (ages 15 to 17), and adults (ages 18 and above); 446 children (312 diagnosed ADHD
      I), 218 adolescents (163 diagnosed ADHD-I), and 1,163 adults (877 ADHD-I). Sleep
      was problematic regardless of age, ADHD subtype, and gender. The type and number
      of sleep problems and fatigue were age dependent. ADHD subtype, gender, fatigue,
      age, and sleep (sleep onset, unrefreshing sleep, sleep maintenance) were
      significant variables affecting neuropsychological test performance (sequencing,
      cognitive flexibility, slow- and fast-paced input, divided attention, whole brain
      functioning). Findings suggest that ADHD involves numerous factors and symptoms
      beyond attention, such as sleep which interacts differently dependent upon age.

PMID- 24897899
TI  - Taking pleasure at another's misfortune: the implicit Schadenfreude of disaster
      spectators.
AB  - Implicit Schadenfreude of disaster spectators, with augmentation of implicit self
      esteem and higher reward responsiveness as indicators, and the influence of
      insecurity and masculinity was explored in two studies. Both studies were
      conducted under conditions without any clearly legitimizing factors. Experimental
      (priming with disaster video) and control (priming with neutral video) groups
      were compared using the Implicit Association Test in Study 1, the results of
      which showed augmentation of implicit self-esteem in the experimental group. In
      Study 2, participants who read and believed a fabricated news report of fire
      disaster via a local area network website showed higher reward responsiveness in
      a reward-based signal-detection task. Other results showed that insecurity
      negatively predicted the augmentation of implicit self-esteem and reward
      responsiveness, while masculinity only negatively predicted the augmentation of
      implicit self-esteem.

PMID- 24897900
TI  - Framing unauthorized immigrants: the effects of labels on evaluations.
AB  - In the U.S. media, unauthorized immigrants are often interchangeably referred to
      as "illegal aliens," "illegal immigrants," and undocumented immigrants." In spite
      of formal equivalence, these terms carry different connotations, but the effects
      of these labels on people's attitudes toward immigrants are not well documented.
      In this replication study, 274 undergraduate students in psychology responded to
      one of three randomly distributed versions of a 20-item scale measuring attitudes
      toward unauthorized immigration. The items in the three scale versions varyingly
      referred to immigrants using the three terms. Results showed differences in
      attitudes toward unauthorized immigration between all experimental conditions.
      The label "illegal immigrants" yielded significantly less positive attitudes
      compared to the label "undocumented immigrants," and respondents exposed to the
      label "illegal aliens" showed the most positive attitudes. Furthermore, the
      effects of the experimental conditions were not moderated by the respondents'
      patriotism, sex, or own immigrant background.

PMID- 24897901
TI  - Measuring the differences in pairs' marital forgiveness scores: construct
      validity and links with relationship satisfaction.
AB  - This study examined the reliability and validity of a Turkish version for the
      Marital Dispositional Forgiveness Scale (MDFS). 104 married couples (M age = 36.6
      yr., SD = 9.4) living in Turkey completed the Turkish versions of the MDFS and
      the Relationship Assessment Scale (RAS). Cronbach's coefficients a for negative
      dimension (wives = .82, husbands = .80) and positive dimension (wives = .80,
      husbands = .79) were adequate. A correlation between the MDFS and RAS scores
      indicated significant associations, stronger for the positive dimension than the
      negative dimension, supporting the external validity of the MDFS.

PMID- 24897902
TI  - Effect of hair ornamentation on helping.
AB  - Previous research has found that restaurant waitresses wearing flowers in their
      hair received higher tips. Here, the effect of hair ornamentation on responses to
      an explicit request for help was assessed. Two female confederates wearing a
      barrette with or without a flower asked 240 passersby (120 men, 120 women;
      apparently 30 to 40 years of age) in the street for bus fare change. The uccess
      rate was 76.7% when they wore the ornamentation and only 50.8% without the
      ornamentation. Both men and women more readily helped those with the hair
      ornamentation.

PMID- 24897904
TI  - The priming effect of military service on creativity performance.
AB  - This study investigated the service priming effect on creativity performance. In
      three experiments, the service priming was manipulated in three ways (Army
      priming, Air Force priming, and a Neutral condition). Participants' performances
      on the Chinese Remote Associates Test (CRAT), insight problems, and critical
      thinking problems were accordingly measured in each experiment. Results showed
      that the Air Force priming improved creativity and the Army priming enhanced
      critical thinking. The results suggest that the constructions and processes of
      these two manipulations are different. In addition, results also suggested that
      the branch of military service moderates the relationship between the service
      priming and the performance of creativity.

PMID- 24897903
TI  - Emotional engagement and school adjustment in late childhood: the relationship
      between school liking and school belonging in Japan.
AB  - This study examined the relationship between school adjustment and emotional
      engagement in late childhood. Participants were Grade 5 and 6 Japanese children
      (N = 304; 164 boys, 200 girls). The School Liking and Avoidance Questionnaire
      (SLAQ) was used to measure children's emotional adjustment to school. The School
      Adjustment Scale, which was used to assess emotional engagement, consists of four
      factors: "friendships," "school work," "teacher-child relationships," and "school
      in general." The last factor was used to measure school belonging.

PMID- 24897905
TI  - Personality variables as predictors of Facebook usage.
AB  - This study investigates the role of personality factors as predictors of Facebook
      usage. Data concerning Facebook usage and personality factors from 654 Facebook
      users were gathered using a web survey. Using path analysis, the results showed
      Openness was a predictor of Facebook early adoption, Conscientiousness with
      sparing use, Extraversion with long sessions and abundant friendships, and
      Neuroticism with high frequency of sessions. The possible role of Agreeableness
      in predicting low session frequency and friendships needs further validation.

PMID- 24897906
TI  - Facilitating role of 3D multimodal visualization and learning rehearsal in memory
      recall.
AB  - The present study investigated the influence of 3D multimodal visualization and
      learning rehearsal on memory recall. Participants (N = 175 college students
      ranging from 21 to 25 years) were assigned to different training conditions and
      rehearsal processes to learn a list of 14 terms associated with construction of a
      wood-frame house. They then completed a memory test determining their cognitive
      ability to free recall the definitions of the 14 studied terms immediately after
      training and rehearsal. The audiovisual modality training condition was
      associated with the highest accuracy, and the visual- and auditory-modality
      conditions with lower accuracy rates. The no-training condition indicated little
      learning acquisition. A statistically significant increase in performance
      accuracy for the audiovisual condition as a function of rehearsal suggested the
      relative importance of rehearsal strategies in 3D observational learning.
      Findings revealed the potential application of integrating virtual reality and
      cognitive sciences to enhance learning and teaching effectiveness.

PMID- 24897907
TI  - Forming impressions: effects of facial expression and gender stereotypes.
AB  - The present study of 138 participants explored how facial expressions and gender
      stereotypes influence impressions. It was predicted that images of smiling women
      would be evaluated more favorably on traits reflecting warmth, and that images of
      non-smiling men would be evaluated more favorably on traits reflecting
      competence. As predicted, smiling female faces were rated as more warm; however,
      contrary to prediction, perceived competence of male faces was not affected by
      facial expression. Participants' female stereotype endorsement was a significant
      predictor for evaluations of female faces; those who ascribed more strongly to
      traditional female stereotypes reported the most positive impressions of female
      faces displaying a smiling expression. However, a similar effect was not found
      for images of men; endorsement of traditional male stereotypes did not predict
      participants' impressions of male faces.

PMID- 24897908
TI  - Sport fans: evaluating the consistency between implicit and explicit attitudes
      toward favorite and rival teams.
AB  - Sport fans often foster very positive attitudes for their favorite teams and less
      favorable attitudes for opponents. The current research was designed to evaluate
      the consistency that might exist between implicit and explicit measures of those
      attitudes. College students (24 women, 16 men) performed a version of the
      Implicit Association Test related to their favorite and rival teams. Participants
      also reported their attitudes for these teams explicitly, via self-report
      instruments. When responding to the IAT, participants' responses were faster when
      they paired positive words with concepts related to favorite teams and negative
      words with rival teams, indicating implicit favorability for favorite teams and
      implicit negativity for rival teams. This pattern of implicit favorability and
      negativity was consistent with what participants reported explicitly via self
      report. The importance of evaluating implicit attitudes and the corresponding
      consistency with explicit attitudes are discussed.

PMID- 24897909
TI  - Body-tanning attitudes among female college students.
AB  - This study investigated the attitudes of body-tanning behaviors: suntanning,
      tanning bed, tanning spray, and sunless tanning product use. Data collected from
      208 female college students (M age = 19.8 yr., SD = 2.0; M weight = 63.3 kg, SD =
      2.0; M height = 165.9 cm, SD = 8.1) online. The questionnaire comprised four
      constructs: appearance-based, health-based, and emotion-based tanning attitudes,
      and body-tanning behaviors. Both appearance-based and emotion-based pro-tanning
      attitudes were associated with significantly higher body-tanning behaviors.
      However, health-based pro-tanning attitudes did not significantly affect body
      tanning behaviors. The results from both UV- and non-UV exposure-related tanning
      behaviors provide future intervention strategies, such as establishing a positive
      body image without a tan and identifying negative emotional consequences as a
      result of tanning.

PMID- 24897911
TI  - The role of brand trust in male customers' relationship to luxury brands.
AB  - This study examined the role of brand trust in customers' luxury brand
      consumption behavior. Perceived value and brand satisfaction were presented
      within a framework as antecedents of brand trust, while brand loyalty and brand
      risk were presented as consequences. A face-to-face survey was administered to a
      sample (N = 400) of men between 25 and 54 years of age who had purchased luxury
      brand and non-luxury brand suits within the previous three months. The results
      showed the greater the hedonic value on brand satisfaction, the greater the
      influence of brand satisfaction on brand trust, and the greater was the effect of
      brand trust on brand loyalty for luxury brands as compared with non-luxury
      brands. Similar patterns are identified between luxury and non-luxury brands for
      the positive relationship between utilitarian value and brand satisfaction and
      the negative relationship between brand trust and brand risk.

PMID- 24897910
TI  - Attentional switching in intellectually gifted and average children: effects on
      performance and ERP.
AB  - The study compared the performance and brain activity of children who were
      intellectually gifted or of average intelligence. 13 intellectually gifted (4
      girls, 9 boys; M age = 12.0 yr., SD = 0.2) and 13 average children (5 girls, 8
      boys; M age = 11.9 yr., SD = 0.3) participated in a task-switching experiment.
      The children performed a task repeatedly (single-trial blocks) or switched
      between two different tasks (mixed-trial blocks). Intellectually gifted children
      performed quicker than the average group for both mixed and single-trial blocks.
      The electroencephalography P300 amplitude was larger in the mixed compared to the
      single-trial condition, but this effect was observed only in the gifted children.
      The results support the notion that gifted children are characterized by a faster
      maturation that leads to an 'adult-like' brain activity.

PMID- 24897912
TI  - Role of career decision-making self-efficacy and risk of career options on career
      decision-making of Chinese graduates.
AB  - This study investigated the influence of Chinese graduates' career decision
      making self-efficacy (CDMSE) and the moderating effect of career options on
      career decisions. Graduates (92 men, 119 women, 5 unreported gender; M age = 223
      yr., SD = 1.2) from four different types of universities in Zhejiang Province
      participated in the study. CDMSE was measured with the CDMSE Scale for University
      Students, and participants rated their choices on 3 career options with different
      levels of risk. The results showed that participants were more likely to choose a
      high-risk option, and that career options moderated the relation between
      graduates' CDMSE and career decision. Graduate career counseling programs should
      encourage students to develop more reasonable career goals that match their
      skills.

PMID- 24897913
TI  - Stress appraisal, coping, and work engagement among police recruits: an
      exploratory study.
AB  - This study investigated the influence of stress appraisal and coping on work
      engagement levels (Absorption, Vigour, and Dedication) of police recruits.
      Participants were 387 men, ages 20 to 33 yr. (M = 24.1, SD = 2.4), in their last
      month of academy training before becoming police officers. Partially in support
      of predictions, work engagement was associated with Stressor control perceived,
      but not Stress intensity experienced over a self-selected stressor. Although the
      three dimensions of work engagement were explained by Stressor control and
      coping, Absorption was the dimension better explained by these variables. Police
      recruits reporting higher Absorption, Vigour, and Dedication reported using more
      Active coping and less Behavioural disengagement. Results showed that stress
      appraisal and coping are important variables influencing work engagement among
      police recruits. Findings suggested that future applied interventions fostering
      work engagement among police recruits should reinforce perceptions of control
      over a stressor as well as Active coping strategies.

PMID- 24897914
TI  - Emotion dysregulation, problem-solving, and hopelessness.
AB  - A sample of 87 Turkish undergraduate students was administered scales to measure
      hopelessness, problem-solving skills, emotion dysregulation, and psychiatric
      symptoms. All of the scores from these scales were strongly associated. In a
      multiple regression, hopelessness scores were predicted by poor problem-solving
      skills and emotion dysregulation.

PMID- 24897915
TI  - Measured anatomical distributions of solar UVR on strawberry production workers
      in Italy.
AB  - The exposure of outdoor workers to solar ultraviolet radiation (UVR) has been
      known for some time. Measurements of erythemally weighted UVR are usually related
      to days of exposure and to the anatomical distribution of UVR on the human body.
      The aim of this research is to describe the UVR exposure of workers during a
      strawberry production cycle in order to assess the UVR hazard and to identify the
      highest exposure in the anatomical distribution of UVR on the body during an
      entire agricultural production cycle. This research was carried out on the
      experimental farm (Azienda Agraria Didattico-Sperimentale) of Universita
      Politecnica delle Marche in Agugliano, Italy. A spectrometer was used to measure
      UVR, and electronic dosimeters were used to record UVR exposure. The measurements
      were carried out on all working days of the strawberry production cycle in 2012
      during daily peak UVR levels. The daily UVR exposure geometric mean and the
      percentage ambient UVR in the strawberry production cycle were calculated and
      analyzed to assess the hazard for workers during the entire production cycle. The
      nape of the neck was the anatomical site most exposed to UVR. The mean daily UVR
      exposure on the nape of the neck was higher than 1.50 SED, the minimum value
      required to produce perceptible erythema in unacclimatized white skin, and a
      maximum value of 2.29 SED was measured. Real-time exposure data suggest that it
      may be useful to remind workers of the risks associated with UVR exposure.

PMID- 24897916
TI  - Region of birth, sex, and agricultural work of immigrant Latino farm workers: the
      MICASA study.
AB  - Agricultural work is hazardous, and immigrant workers perform the majority of
      production tasks, yet there are few data describing agricultural work and use of
      protective measures by demographic characteristics. We examined cross-sectionally
      the influence of region of birth (Mexico vs. Central America) and sex on
      agricultural work and use of protective measures in the MICASA cohort of
      immigrant Latino farm workers in Mendota, California. Of 445 participants, 293
      (65.8%) were born in Mexico (163 men, 130 women) and 152 (34.2%) were born in
      Central America (80 men, 72 women). Men worked on average 74.4 more days than
      women (95% CI 62.0, 86.9) and were more likely to perform tasks requiring high
      levels of training or strength, such as machine operation, pruning, picking,
      planting, and irrigation; more likely to work in dusty conditions; and more
      likely to work directly with pesticides. Women predominated in packing.
      Respondents from Mexico were more likely to work with tomatoes and less likely to
      work with melon and lettuce. Central America-born respondents were less likely to
      engage in planting, irrigation, and pesticide use. Use of task-appropriate
      personal protective measures on at least a half-time basis was rare, with the
      exception of persons working with pesticides (a group limited to men) and for
      facial scarves among Central American women. Further work should focus on
      identifying barriers to use of preventive measures and programs to further their
      use. Educational models accounting for cultural factors and driving social norm
      change, employer engagement, and use of community health workers (promotores) may
      be helpful in promoting use of preventive measures.

PMID- 24897917
TI  - Development of a safety decision-making scenario to measure worker safety in
      agriculture.
AB  - Human factors play an important role in the management of occupational safety,
      especially in high-hazard workplaces such as commercial grain-handling
      facilities. Employee decision-making patterns represent an essential component of
      the safety system within a work environment. This research describes the process
      used to create a safety decision-making scenario to measure the process that
      grain-handling employees used to make choices in a safety-related work task. A
      sample of 160 employees completed safety decision-making simulations based on a
      hypothetical but realistic scenario in a grain-handling environment. Their
      choices and the information they used to make their choices were recorded.
      Although the employees emphasized safety information in their decision-making
      process, not all of their choices were safe choices. Factors influencing their
      choices are discussed, and implications for industry, management, and workers are
      shared.

PMID- 24897918
TI  - Estimating the effect of selected predictors on agricultural confined-space
      hazard perceptions of Utah farm owner/operators.
AB  - The purpose of this study was to assess how selected variables affect the
      confined-space hazard perceptions of farmers in Utah. A confined space was
      defined as "any space found in an agricultural workplace that was not designed or
      intended as a regular workstation, has limited or restricted means of entry or
      exit, and contains potential physical and toxic hazards to workers who
      intentionally or unintentionally enter the space" (proposed by NCERA-197, 18 May
      2011, draft copy). A total of 303 out of 327 farm owner/operators provided
      complete surveys that were used in the analysis. The state of Utah was grouped
      into five regions in this study: central, east, northeast, northwest, and
      southwest. Grain and dairy production comprised 48.7% of the operations
      responding to the survey. The general linear modeling (GLM) procedure in SAS 9.3
      was used to select the models on hazard perception scores for the five studied
      regions. Interested predictors included response type, production type, safety
      planning, and injury concerns. Animal production operations had the highest
      average number of confined spaces (micro = 4, SD = 2.7). Regionally, the
      northwest region had the highest average number of confined spaces (micro = 4, SD
      = 2.5). The variables contributing most to confined-space hazard perceptions were
      injury and death concerns while working alone in confined spaces. Three factors
      were generated using principle factor analysis (PFA) with orthogonal varimax
      rotation. Results suggested that factors affect hazard perceptions differently by
      region. We conclude that outreach and educational efforts to change safety
      behaviors regarding confined-space hazards should be strategically targeted for
      each region based on predicting factors. The result can assist agricultural
      safety and health professionals in targeting agricultural producers' social
      networks to address human factors such as worker attitudes and/or lack of skills
      or knowledge that effect hazard perceptions of confined spaces in agriculture.

PMID- 24897919
TI  - Isolated benign primary cutaneous plasmacytosis.

PMID- 24897920
TI  - Dimer adsorption on a (100) nanotube of arbitrary diameter, with first- and
      second-neighbor interactions.
AB  - Dimer adsorption on an infinitely long (100) or square lattice nanotube of fixed
      lattice constant and arbitrary number M of sites in its normal cross section is
      considered with first- and second-neighbor interaction energies, V and W,
      respectively. An increase in M keeping the lattice constant fixed corresponds to
      a nanotube with increasing diameter. The system is at thermodynamic equilibrium
      and relatively low temperature in order to determine all of the possible
      crystallization patterns or phases that may exist. Under these conditions, the
      energy phase space diagram is two-dimensional, and the dimensionless parameters
      are u = W/|V| and v = MU/|V|, where MU is the sum of the chemical potential
      energy, MU', of a dimer and the dimer-substrate interaction energy V0. The low
      temperature energy phase diagram is numerically generated using a transfer matrix
      method adapted to the present problem. For both attractive and repulsive first
      neighbors, it is M-independent for M even, and its M-dependence when M is odd is
      established. As a consistency check, the infinite odd-M limit matches exactly the
      M-independent phase diagram for even M. The knowledge of the boundaries of the
      regions in the phase diagram where these phases occur and the knowledge of their
      respective occupational configurations are particularly useful information when
      experimental data on dimer adsorption on square nanotubes become available. 

PMID- 24897921
TI  - Early postpartum breast-feeding outcomes and breast-feeding self-efficacy in
      Turkish mothers undergoing vaginal birth or cesarean birth with different types
      of anesthesia.
AB  - PURPOSE: To compare the breast-feeding outcomes and breast-feeding self-efficacy,
      in the first 24 postpartum hours, of mothers who underwent vaginal birth,
      cesarean birth with epidural anesthesia, and cesarean birth with general
      anesthesia. METHODS: A comparative study was conducted in Turkey. A total of 334
      mothers participated. Data were evaluated through descriptive data form, breast
      feeding outcomes form, and the Breastfeeding Self-Efficacy Scale. FINDINGS: It
      was observed that the mothers who had cesarean birth with general anesthesia
      experienced more breast-feeding problems. With regard to breast-feeding self
      efficacy, all the groups were similar. CONCLUSION: For reducing breast-feeding
      problems, nurses should provide more care and support to mothers undergoing
      cesarean birth. Therefore, the fact that the breast-feeding self-efficacy was
      similar among the groups might be related to culture.

PMID- 24897922
TI  - Glossal pigmentation caused by the simultaneous uptake of iron and tea.

PMID- 24897923
TI  - EXAFS study into the speciation of metal salts dissolved in ionic liquids and
      deep eutectic solvents.
AB  - The speciation of metals in solution controls their reactivity, and this is
      extremely pertinent in the area of metal salts dissolved in ionic liquids. In the
      current study, the speciation of 25 metal salts is investigated in four deep
      eutectic solvents (DESs) and five imidazolium-based ionic liquids using extended
      X-ray absorption fine structure. It is shown that in diol-based DESs M(I) ions
      form [MCl2](-) and [MCl3](2-) complexes, while all M(II) ions form [MCl4](2-)
      complexes, with the exception of Ni(II), which exhibits a very unusual
      coordination by glycol molecules. This was also found in the X-ray crystal
      structure of the compound [Ni(phen)2(eg)]Cl2.2eg (eg = ethylene glycol). In a
      urea-based DES, either pure chloro or chloro-oxo coordination is observed. In
      [C6mim][Cl] pure chloro complexation is also observed, but coordination numbers
      are smaller (typically 3), which can be explained by the long alkyl chain of the
      cation. In [C2mim][SCN] metal ions are entirely coordinated by thiocyanate,
      either through the N or the S atom, depending on the hardness of the metal ion
      according to the hard-soft acid-base principle. With weaker coordinating anions,
      mixed coordination between solvent and solute anions is observed. The effect of
      hydrate or added water on speciation is insignificant for the diol-based DESs and
      small in other liquids with intermediate or strong ligands. One of the main
      findings of this study is that, with respect to metal speciation, there is no
      fundamental difference between deep eutectic solvents and classic ionic liquids. 

PMID- 24897924
TI  - Wound healing in US medical school curricula.
AB  - Approximately 6.5 million Americans suffer from nonhealing wounds. As physicians
      are increasingly expected to manage chronic wounds, the degree to which
      formalized wound care education exists as a clinical rotation is unclear. For the
      first time, the prevalence and characteristics of formal wound electives offered
      by US medical schools are documented. Online surveys were distributed to 134 US
      medical schools and to the 74 medical students who completed the wound healing
      elective at the University of Miami regarding their experiences. School response
      rate was 41% (n = 55). We found that out of 55 schools, only 7 schools offered a
      formal wound healing elective. The University of Miami was the only school to
      include a surgical component. Students' response rate was 39% (n = 29). After
      completing the elective, 20 students (69%) felt confident in their knowledge of
      surgical and medical wound management. A majority of students (76%, n = 22) felt
      that the elective was an important part of the medical school curriculum. In
      conclusion, we found very few schools offer a formal wound elective and recommend
      medical schools in formalizing this education through clinical electives.
      Education should be team-based and multidisciplinary; evidence exists that this
      is the best approach to managing chronic wounds. Basic tenets of wound care, both
      medical and surgical, should be emphasized.

PMID- 24897925
TI  - Stress response or beneficial temperature acclimation: transcriptomic signatures
      in Antarctic fish (Pachycara brachycephalum).
AB  - Research on the thermal biology of Antarctic marine organisms has increased
      awareness of their vulnerability to climate change, as a flipside of their
      adaptation to life in the permanent cold and their limited capacity to acclimate
      to variable temperatures. Here, we employed a species-specific microarray of the
      Antarctic eelpout, Pachycara brachycephalum, to identify long-term shifts in gene
      expression after 2 months of acclimation to six temperatures between -1 and 9 
      degrees C. Changes in cellular processes comprised signalling, post-translational
      modification, cytoskeleton remodelling, metabolic shifts and alterations in the
      transcription as well as translation machinery. The magnitude of transcriptomic
      responses paralleled the change in whole animal performance. Optimal growth at 3 
      degrees C occurred at a minimum in gene expression changes indicative of a
      balanced steady state. The up-regulation of ribosomal transcripts at 5  degrees C
      and above was accompanied by the transcriptomic activation of differential
      protein degradation pathways, from proteasome-based degradation in the cold
      towards lysosomal protein degradation in the warmth. From 7  degrees C upwards,
      increasing transcript levels representing heat-shock proteins and an acute
      inflammatory response indicate cellular stress. Such patterns may contribute to a
      warm-induced energy deficit and a strong weight loss at temperatures above 6 
      degrees C. Together, cold or warm acclimation led to specific cellular
      rearrangements and the progressive development of functional imbalances beyond
      the optimum temperature. The observed temperature-specific expression profiles
      reveal the molecular basis of thermal plasticity and refine present understanding
      of the shape and positioning of the thermal performance curve of ectotherms on
      the temperature scale. 

PMID- 24897926
TI  - Androgen deficiency as a biological determinant of frailty: hope or hype?
AB  - The role of androgen deficiency as a biological determinant of frailty has
      received considerable attention. Cross-sectional studies have shown that low
      bioavailable testosterone (BT) is associated with prevalent frailty. High levels
      of luteinizing hormone and sex hormone binding globulin are also associated with
      prevalent frailty. Longitudinal studies have had mixed results, suggesting, for
      the most part, that a decline in BT over time is associated with progression of
      frailty. A number of potential biases were found in the current body of evidence,
      including misclassification bias (due to testosterone assays that were
      insensitive in lower ranges), selection bias (due to preferential inclusion of
      healthier individuals), and residual confounding (due to correlation of low
      testosterone with several disease states and adverse health characteristics).
      Consideration of these biases is vital to ensure that future epidemiological
      studies and interventional trials generate valid conclusions. 

PMID- 24897927
TI  - Parental attachment style: examination of links with parent secure base provision
      and adolescent secure base use.
AB  - The secure base construct represents one of attachment theory's most important
      contributions to our understanding of parent-child relationships and child
      development. The present study represents the first examination of how parents'
      self-reported attachment styles relate to parental secure base provision and
      adolescent (mean age = 16.6 years, SE = .59) secure base use during an observed
      parent-adolescent interaction. Further, the present study is the first to examine
      how fathers', as well as mothers', attachment styles relate to observed behavior
      in a parent-child interaction. At the bivariate level, maternal avoidance, but
      not anxiety, was negatively associated with observed adolescent secure base use.
      In addition, path analysis revealed that maternal avoidance was indirectly
      related to less adolescent secure base use through mothers' self-reported hostile
      behavior toward their adolescents and through adolescents' less positive
      perceptions of their mothers. Further, paternal anxiety, but not avoidance, was
      indirectly related to less adolescent secure base use through fathers' self
      reported hostile behavior toward their adolescents. No significant findings
      emerged in relation to parental secure base provision. We discuss these results
      in the context of attachment theory and suggest directions for future research.

PMID- 24897930
TI  - Encapsulating MWNTs into hollow porous carbon nanotubes: a tube-in-tube carbon
      nanostructure for high-performance lithium-sulfur batteries.
AB  - A tube-in-tube carbon nanostructure (TTCN) with multi-walled carbon nanotubes
      (MWNTs) confined within hollow porous carbon nanotubes is synthesized for Li-S
      batteries. The structure is designed to enhance the electrical conductivity,
      hamper the dissolution of lithium polysulfide, and provide large pore volume for
      sulfur impregnation. As a cathode material for Li-S batteries, the S-TTCN
      composite with 71 wt% sulfur content delivers high reversible capacity, good
      cycling performance as well as excellent rate capabilities. 

PMID- 24897928
TI  - The impact of HAART initiation timing on HIV-TB co-infected patients, a
      retrospective cohort study.
AB  - BACKGROUND: Optimal timing for initiating highly active antiretroviral therapy
      (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to
      evaluate the impact of different timing of HAART initiation on TB outcome of HIV
      infected adults in Taiwan. METHODS: A population-based retrospective cohort study
      was conducted through linking the HIV and TB registries of Taiwan Centers for
      Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected
      patients, including the presence of immune reconstitution inflammatory syndrome
      (IRIS), was collected through medical records review. The outcome of interest was
      all-cause mortality within 1 year following TB diagnosis. The Cox proportional
      hazard model was used to explore the probability of death and IRIS after TB
      diagnosis by adjusting for confounding factors and factors of interest. The
      probability of survival and TB IRIS were calculated by the Kaplan-Meier method
      and compared between different HAART initiation timing groups by the log-rank
      test. RESULTS: There were 229 HIV-TB co-infected patients included for analysis
      and 60 cases (26.2%) died within one year. Besides decreasing age and increasing
      CD4 lymphocyte count, having started HAART during TB treatment was significantly
      associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06
      0.21). As to the timing of HAART initiation, there was only non-significant
      benefit on survival among cases initiating HAART within 15 days, at 16-30 days
      and at 31-60 days of TB treatment than initiating after 60 days. Cases with HAART
      initiated after 30 days had lower risk in developing IRIS than cases with HAART
      initiated earlier. Cases with IRIS had significantly higher rate of re
      hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days
      vs. 18.5 days, p < 0.01). CONCLUSION: The present study found that starting HAART
      during TB treatment is associated with better one-year survival, although earlier
      initiation within 60 days of TB treatment did not show statistical differences in
      survival than later initiation. Initiation of HAART within 30 days appeared to
      increase the risk of IRIS. Deferring HAART to 31-60 days of TB treatment might be
      optimal after considering the risks and benefits.

PMID- 24897929
TI  - Genome-wide analysis of alternative splicing of pre-mRNA under salt stress in
      Arabidopsis.
AB  - BACKGROUND: Alternative splicing (AS) of precursor mRNA (pre-mRNA) is an
      important gene regulation process that potentially regulates many physiological
      processes in plants, including the response to abiotic stresses such as salt
      stress. RESULTS: To analyze global changes in AS under salt stress, we obtained
      high-coverage (~200 times) RNA sequencing data from Arabidopsis thaliana
      seedlings that were treated with different concentrations of NaCl. We detected
      that ~49% of all intron-containing genes were alternatively spliced under salt
      stress, 10% of which experienced significant differential alternative splicing
      (DAS). Furthermore, AS increased significantly under salt stress compared with
      under unstressed conditions. We demonstrated that most DAS genes were not
      differentially regulated by salt stress, suggesting that AS may represent an
      independent layer of gene regulation in response to stress. Our analysis of
      functional categories suggested that DAS genes were associated with specific
      functional pathways, such as the pathways for the responses to stresses and RNA
      splicing. We revealed that serine/arginine-rich (SR) splicing factors were
      frequently and specifically regulated in AS under salt stresses, suggesting a
      complex loop in AS regulation for stress adaptation. We also showed that
      alternative splicing site selection (SS) occurred most frequently at 4
      nucleotides upstream or downstream of the dominant sites and that exon skipping
      tended to link with alternative SS. CONCLUSIONS: Our study provided a
      comprehensive view of AS under salt stress and revealed novel insights into the
      potential roles of AS in plant response to salt stress.

PMID- 24897931
TI  - PI3K/AKT signaling pathway and cancer: an updated review.
AB  - Despite development of novel agents targeting oncogenic pathways, matching
      targeted therapies to the genetic status of individual tumors is proving to be a
      daunting task for clinicians. To improve the clinical efficacy and to reduce the
      toxic side effects of treatments, a deep characterization of genetic alterations
      in different tumors is required. The mutational profile often evidences a gain of
      function or hyperactivity of phosphoinositide 3-kinases (PI3Ks) in tumors. These
      enzymes are activated downstream tyrosine kinase receptors (RTKs) and/or G
      proteins coupled receptors (GPCRs) and, via AKT, are able to induce mammalian
      target of rapamycin (mTOR) stimulation. Here, we elucidate the impact of class I
      (p110alpha, beta, gamma, and delta) catalytic subunit mutations on AKT-mediated
      cellular processes that control crucial mechanisms in tumor development.
      Moreover, the interrelation of PI3K signaling with mTOR, ERK, and RAS pathways
      will be discussed, exploiting the potential benefits of PI3K signaling inhibitors
      in clinical use.

PMID- 24897932
TI  - Analysis and pharmacokinetic study of polyphyllin H in beagle dog plasma after
      oral administration of Rhizoma Paridis extracts by LC-MS/MS.
AB  - A highly sensitive, rapid assay method has been developed and validated for the
      analysis of polyphyllin H in beagle dog plasma with liquid chromatography coupled
      to tandem mass spectrometry with electrospray ionization in the positive-ion
      mode. The assay procedure involves extraction of polyphyllin H and ginsenoside Re
      (IS) from beagle dog plasma. Chromatographic separation was carried out on an
      Agilent Zorbax XDB-C18 (100 * 2.1 mm, 1.8MUm) column by isocratic elution with
      acetonitrile and water (50:50, v/v) at a flow rate of 0.25 mL/min with a total
      run time of 2.5 min. The MS/MS ion transitions monitored were m/z 869.60 ->
      869.60 for polyphyllin H and m/z 969.60 -> 969.60 for IS. [corrected] Linear
      responses were obtained for polyphyllin H ranging from 1 to 50 ng/mL. The intra
      and inter-day precisions (RSDs) <1.77 and 3.39% and the extraction recovery
      ranged from 91.89 to 93.33% with RSD <2.68%. Stability studies showed that
      polyphyllin H was stable in the preparation and analytical process. The results
      indicated that the validated method was successfully used to determine the
      concentration-time profiles of polyphyllin H.

PMID- 24897934
TI  - Uncovering the life and work of Louis Tribondeau: a pioneer in dermatology and
      biochemistry.

PMID- 24897933
TI  - Early social isolation provokes electrophysiological and structural changes in
      cutaneous sensory nerves of adult male rats.
AB  - Sensory and social deprivation from the mother and littermates during early life
      disturbs the development of the central nervous system, but little is known about
      its effect on the development of the peripheral nervous system. To assess
      peripheral effects of early isolation, male rat pups were reared artificially in
      complete social isolation (AR); reared artificially with two same-age
      conspecifics (AR-Social); or reared by their mothers and with littermates (MR).
      As adults, the electrophysiological properties of the sensory sural (SU) nerve
      were recorded. We found that the amplitude and normalized area (with respect to
      body weight) of the compound action potential (CAP) response provoked by single
      electrical pulses of graded intensity in the SU nerves of AR animals were shorter
      than the CAP recorded in SU nerves from MR and AR-Social animals. The slope of
      the stimulus-response curve of AR SU nerves was smaller than that of the other
      nerves. The histological characterization of axons in the SU nerves was made and
      showed that the myelin thickness of axons in AR SU nerves was significant lower
      (2-7um) than that of the axons in the other nerves. Furthermore, the area and
      axon diameter of SU nerves of both AR and AR-Social animals were significant
      lower than in MR animals. This is the first report to show that maternal and
      littermate deprivation by AR disturbs the development of the myelination and
      electrophysiological properties of axons in the SU nerve; the replacement of
      social cues prevents most of the effects.

PMID- 24897935
TI  - Targeted highly sensitive detection/eradication of multi-drug resistant
      Salmonella DT104 through gold nanoparticle-SWCNT bioconjugated nanohybrids.
AB  - Monoclonal antibody-conjugated sphere-shaped gold nanoparticles were combined
      with single-walled carbon nanotubes (SWCNTs) to create a nanohybrid system to
      selectively detect and eradicate multiple drug resistant Salmonella (MDRS)
      typhimurium DT104 bacteria. The Raman signal intensity from Rhodamine 6G (Rh6G)
      modified monoclonal AC04 antibody SWCNTs-gold nanoparticle (SWCNT-GNPs) hybrid
      provided a SERS enhancement by several orders of magnitude to detect the MDRS
      bacteria over the GNP system. A targeted photothermolysis experiment using 670 nm
      light at 2 W cm(-2) for 15 min, resulted in selective and irreparable damage to
      more than 99% Salmonella DT104 at the concentration of 10(5) CFU mL(-1). In
      comparison to solely SWCNTs or GNPs, our SWCNT-GNPs nanohybrids have also shown a
      better photothermal efficiency. 

PMID- 24897936
TI  - Fluid-structure interaction analysis of the left coronary artery with variable
      angulation.
AB  - The aim of this study is to elucidate the correlation between coronary artery
      branch angulation, local mechanical and haemodynamic forces at the vicinity of
      bifurcation. Using a coupled fluid-structure interaction (FSI) modelling
      approach, five idealized left coronary artery models with various angles ranging
      from 70 degrees  to 110 degrees  were developed to investigate the influence of
      branch angulations. In addition, one CT image-based model was reconstructed to
      further demonstrate the medical application potential of the proposed FSI
      coupling method. The results show that the angulation strongly alters its
      mechanical stress distribution, and the instantaneous wall shear stress
      distributions are substantially moderated by the arterial wall compliance. As
      high tensile stress is hypothesized to cause stenosis, the left circumflex side
      bifurcation shoulder is indicated to induce atherosclerotic changes with a high
      tendency for wide-angled models. 

PMID- 24897937
TI  - Gremlin-2 is a BMP antagonist that is regulated by the circadian clock.
AB  - Tendons are prominent members of the family of fibrous connective tissues (FCTs),
      which collectively are the most abundant tissues in vertebrates and have crucial
      roles in transmitting mechanical force and linking organs. Tendon diseases are
      among the most common arthropathy disorders; thus knowledge of tendon gene
      regulation is essential for a complete understanding of FCT biology. Here we show
      autonomous circadian rhythms in mouse tendon and primary human tenocytes,
      controlled by an intrinsic molecular circadian clock. Time-series microarrays
      identified the first circadian transcriptome of murine tendon, revealing that
      4.6% of the transcripts (745 genes) are expressed in a circadian manner. One of
      these genes was Grem2, which oscillated in antiphase to BMP signaling. Moreover,
      recombinant human Gremlin-2 blocked BMP2-induced phosphorylation of Smad1/5 and
      osteogenic differentiation of human tenocytes in vitro. We observed dampened
      Grem2 expression, deregulated BMP signaling, and spontaneously calcifying tendons
      in young CLOCKDelta19 arrhythmic mice and aged wild-type mice. Thus, disruption
      of circadian control, through mutations or aging, of Grem2/BMP signaling becomes
      a new focus for the study of calcific tendinopathy, which affects 1-in-5 people
      over the age of 50 years. 

PMID- 24897939
TI  - Inferior vena cava diameter change after intravenous furosemide in patients
      diagnosed with acute decompensated heart failure.
AB  - PURPOSE: Measurement of the inferior vena cava (IVC) diameters may improve
      decision-making for patients hospitalized with acute decompensated heart failure.
      Nevertheless, little is known about how the IVC is affected by loop diuretics. We
      sought to determine if bolus infusions of intravenous furosemide affect IVC
      diameters measured by hand-carried ultrasonography. METHODS: We conducted a
      prospective cohort study at a public teaching hospital from September 2009
      through June 2010. Physician investigators performed IVC ultrasonography on a
      convenience sample of 70 hospitalized adults who were prescribed intravenous
      furosemide for the diagnosis of acute decompensated heart failure. RESULTS:
      Participants' median baseline IVC diameter was 2.38 cm (interquartile range, 1.91
      2.55 cm). At 1-2 hours after furosemide, IVC diameters decreased an average of
      0.21 cm (95% CI, 0.13-0.29 cm) and remained significantly below baseline at 2-3
      hours after furosemide by an average of 0.15 cm (95% CI, 0.07-0.22 cm).
      CONCLUSIONS: IVC diameters of adults diagnosed with acute decompensated heart
      failure become measurably smaller after single doses of intravenous furosemide.
      Whether this represents a true change in volume status has not been studied.

PMID- 24897938
TI  - S-acylation anchors remorin proteins to the plasma membrane but does not
      primarily determine their localization in membrane microdomains.
AB  - Remorins are well-established marker proteins for plasma membrane microdomains.
      They specifically localize to the inner membrane leaflet despite an overall
      hydrophilic amino acid composition. Here, we determined amino acids and post
      translational lipidations that are required for membrane association of remorin
      proteins. We used a combination of cell biological and biochemical approaches to
      localize remorin proteins and truncated variants of those in living cells and
      determined S-acylation on defined residues in these proteins. S-acylation of
      cysteine residues in a C-terminal hydrophobic core contributes to membrane
      association of most remorin proteins. While S-acylation patterns differ between
      members of this multi-gene family, initial membrane association is mediated by
      protein-protein or protein-lipid interactions. However, S-acylation is not a key
      determinant for the localization of remorins in membrane microdomains. Although
      remorins bind via a conserved mechanism to the plasma membrane, other membrane
      resident proteins may be involved in the recruitment of remorins into membrane
      domains. S-acylation probably occurs after an initial targeting of the proteins
      to the plasma membrane and locks remorins in this compartment. As S-acylation is
      a reversible post-translational modification, stimulus-dependent intracellular
      trafficking of these proteins can be envisioned. 

PMID- 24897940
TI  - Near-infrared spectroscopy for examination of prefrontal activation during
      cognitive tasks in patients with major depressive disorder: a meta-analysis of
      observational studies.
AB  - AIMS: Near-infrared spectroscopy has the potential for aiding the diagnosis of
      major depressive disorder. The purpose of this study was to systematically review
      the evidence from observational studies regarding the use of near-infrared
      spectroscopy in patients with major depressive disorder and to identify the
      characteristic pattern of prefrontal lobe activity in major depressive disorder.
      METHODS: medline, PubMed, Cochrane Library and Web of Science databases were
      searched in December 2013. All case-control studies were included. The quality of
      evidence was examined using the Newcastle-Ottawa Quality Assessment Scale. The
      primary outcome measures were the mean oxygenated and deoxygenated hemoglobin
      alterations of the cerebral cortex during cognitive activation periods. The
      standard mean difference for the overall pooled effects across the included
      studies was estimated using random or fixed effect models. The primary outcome
      measures were included in the meta-analysis. RESULTS: Fourteen studies met the
      inclusion criteria. Six studies (n = 692 participants) were included in the
      analysis of the mean oxygenated hemoglobin alterations; the pooled mean
      standardized difference was -0.74 (95% confidence interval, -0.97 to -0.52),
      indicating that patients with major depressive disorder were associated with
      attenuated increase in oxygenated hemoglobin during cognitive activation in the
      prefrontal regions compared to healthy controls. Five studies (n = 668
      participants) were included in the analysis of mean deoxygenated-hemoglobin
      changes; the pooled standardized mean difference was 0.18 (95% confidence
      interval, -0.20 to 0.56). CONCLUSIONS: Using near-infrared spectroscopy
      measurements, we observed that compared to healthy subjects, patients with major
      depressive disorder had significantly lower prefrontal activation during
      cognitive tasks.

PMID- 24897941
TI  - Canine intrahepatic vasculature: is a functional anatomic model relevant to the
      dog?
AB  - OBJECTIVE: To clarify canine intrahepatic portal and hepatic venous system
      anatomy using corrosion casting and advanced imaging and to devise a novel
      functional anatomic model of the canine liver to investigate whether this could
      help guide the planning and surgical procedure of partial hepatic lobectomy and
      interventional radiological procedures. STUDY DESIGN: Prospective experimental
      study. ANIMALS: Adult Greyhound cadavers (n = 8). METHODS: Portal and hepatic
      vein corrosion casts of healthy livers were assessed using computed tomography
      (CT). RESULTS: The hepatic lobes have a consistent hilar hepatic and portal vein
      supply with some variation in the number of intrahepatic branches. For all
      specimens, 3 surgically resectable areas were identified in the left lateral lobe
      and 2 surgically resectable areas were identified in the right medial lobe as
      defined by a functional anatomic model. CONCLUSIONS: CT of detailed acrylic casts
      allowed complex intrahepatic vascular relationships to be investigated and
      compared with previous studies. Improving understanding of the intrahepatic
      vascular supply facilitates interpretation of advanced images in clinical
      patients, the planning and performance of surgical procedures, and may facilitate
      interventional vascular procedures, such as intravenous embolization of
      portosystemic shunts. Functional division of the canine liver similar to human
      models is possible. The left lateral and right medial lobes can be consistently
      divided into surgically resectable functional areas and partial lobectomies can
      be performed following a functional model; further study in clinically affected
      animals would be required to investigate the relevance of this functional model
      in the dog.

PMID- 24897942
TI  - Use of continuous-infusion loop diuretics in critically ill children.
AB  - Loop diuretics are commonly used in critically ill children to achieve
      appropriate fluid balance. They are often administered as a continuous
      intravenous infusion (CI) in hemodynamically unstable children because of fewer
      alterations in central venous pressure, oxygen saturation, and heart rate
      compared with scheduled intermittent dosing. During the past few years, however,
      drug shortages have been reported for bumetanide, torsemide, and furosemide.
      Therefore, to explore the use of alternative agents for CI, we performed a
      literature search to identify articles evaluating the use of furosemide,
      bumetanide, ethacrynic acid, and torsemide CI in critically ill children. The
      search was limited to English-language articles in the MEDLINE (1946-December
      2013), EMBASE (1980-December 2013), and International Pharmaceutical Abstracts
      (1970-December 2013) databases and the Cochrane Database of Systematic Reviews
      (2005-December 2013). Reference citations from relevant articles were also
      reviewed. A total of 10 reports representing 173 pediatric patients were included
      in the analysis. Most of the reports provided evidence for furosemide, and no
      reports with torsemide were identified. Wide variability in CI dosing was
      reported in these studies. When selecting the loop diuretic CI for critically ill
      patients, clinicians should consider their adverse-event profiles, compatibility
      with other concomitant intravenous infusions, and pharmacoeconomics. Fluid
      balance and urine output should be monitored routinely to ensure appropriate
      response. The lowest initial dose should be used to achieve an appropriate fluid
      balance and target urine output of 1-3 ml/kg/hour while limiting the likelihood
      of toxicity. 

PMID- 24897943
TI  - Medical characteristics of the oldest old: retrospective chart review of patients
      aged 85+ in an academic primary care centre.
AB  - BACKGROUND: The population aged 85 + - the "oldest old" - is now the fastest
      growing age segment in Canada. Although existing research demonstrates high
      health services utilization and medication burden in this population, little
      clinically derived evidence is available to guide care. This is a descriptive
      study in a primary care context seeking to describe the most common health
      conditions and medications used in the "oldest old". METHODS: We conducted a
      retrospective chart review of all family practice patients aged 85+ (N = 564; 209
      males, 355 females) at Sunnybrook Health Sciences Centre in Toronto, Canada.
      Electronic medical records were reviewed for all current chronic conditions and
      medication prescriptions, and then stratified by sex and age subgroup (85-89, 90
      94, 95+) for descriptive analysis. RESULTS: On average, patients experienced 6.4
      concurrent chronic conditions and took 6.8 medications. Most conditions were
      related to cardiovascular (79%) and bone health (65%). Hypertension (65%) was the
      most common condition. Bone-related conditions (e.g. osteoarthritis,
      osteoporosis) and hypothyroidism predominantly affected women, while coronary
      artery disease and type 2 diabetes were more prevalent in men. The top two
      prescribed medications were atorvastatin (33%) and aspirin 81 mg (33%). Males
      were more likely to be prescribed lipid-lowering medications, while females were
      more likely to receive osteoporosis therapy. Patients received less lipid
      lowering therapy with increasing age. CONCLUSIONS: Multimorbidity and
      polypharmacy are highly prevalent in patients in the 85+ age group. The most
      common clinical conditions are related to cardiovascular and bone health, and the
      most commonly prescribed medications are directed towards risk factors for these
      illnesses. In the absence of data to guide clinical decision-making, this study
      provides a first look at the common health concerns and medication profiles in
      this population and reveals trends that give rise to reflections on how clinical
      care for these patients can be improved.

PMID- 24897944
TI  - Copper-mediated pyrazole synthesis from 2,3-allenoates or 2-alkynoates, amines
      and nitriles.
AB  - An efficient copper-mediated three-component reaction of 2,3-allenoates or 2
      alkynoates, amines, and nitriles affording fully substituted pyrazoles with a
      very nice diversity has been developed. A tandem conjugate addition, 1,2
      addition, and N-N bond formation mechanism has been proposed for this diverse
      synthesis of pyrazoles based on mechanistic studies. 

PMID- 24897945
TI  - Beyond 30-day mortality: aligning surgical quality with outcomes that patients
      value.

PMID- 24897946
TI  - Conditioned pain modulation in temporomandibular disorders (TMD) pain patients.
AB  - The aims were to investigate (1) if temporomandibular disorders (TMD) patients
      with temporomandibular joint (TMJ) pain had different conditioned pain modulation
      (CPM) compared with healthy subjects and, (2) if clinical pain characteristics
      influenced CPM. Sixteen TMD pain patients and 16 age-matched healthy subjects
      were participated. A mechanical conditioning stimulus (CS) was applied to
      pericranial muscles provoking a pain intensity of 5/10 on a visual analogue
      scale. Pressure pain thresholds (PPT) and pressure pain tolerance thresholds
      (PPTol) were assessed at masseter, forearm and painful TMJ (only PPT) before,
      during, and 20 min after CS. Data were analyzed with ANOVAs. The correlations
      between CPM effect and ratings of TMD pain intensity on a numerical rating scale
      (NRS) or the pain duration were calculated (correlation coefficient; R). The
      relative PPT and PPTol increases (mean for the three assessment sites) during CS
      were significantly higher than baseline in healthy subjects (43.0 +/- 3.6, 33.0
      +/- 4.0 %; P < 0.001, P < 0.001) but not in the TMD pain patients (4.9 +/- 2.7, 
      1.4 +/- 4.1 %; P = 0.492, P = 1.000) with significant differences between groups
      (P < 0.001). In the patients, the relative PPT changes during CS were not
      significantly higher than baseline at TMJ (5.3 +/- 3.8 %, P = 0.981) and masseter
      (-2.8 +/- 4.8 %, P = 1.000) but significantly higher at forearm (12.3 +/- 4.7 %,
      P = 0.039). No correlation was detected between TMD pain intensity and CPM effect
      (R = -0.261; P = 0.337) or between pain duration and CPM effect (R = -0.423; P =
      0.103) at painful TMJ. These findings indicate that CPM is impaired in TMD pain
      patients especially at sites with chronic pain but not at pain-free sites and
      that the clinical pain characteristics do not influence CPM.

PMID- 24897947
TI  - Mixed observation favors motor learning through better estimation of the model's
      performance.
AB  - Observation contributes to motor learning. It was recently demonstrated that the
      observation of both a novice and an expert model (mixed observation) resulted in
      better learning of a complex spatio-temporal task than the observation of either
      a novice or an expert model alone. In the present study, we sought to determine
      whether the advantage of mixed observation resulted from the development of a
      better error detection mechanism. The results revealed that mixed observation
      resulted in a better estimation of the model's performance than that with other
      regimens of observation. The results also suggest that observational learning is
      improved when observation with knowledge of the results (KR) is followed by an
      observation phase without KR.

PMID- 24897948
TI  - Scabies and bedbugs in hospital outbreaks.
AB  - Scabies and bedbugs are two emerging ectoparasitic infections reported in crowded
      areas, including hospitals. Skin involvement is the main presenting initial
      manifestation for both infections, and the diagnosis is yet challenging for both.
      Topical permethrin is considered the first-line therapy for scabies except for
      crusted scabies which is mainly treated with oral ivermectin. To the contrary,
      treatment of bedbugs is mainly symptomatic. Avoiding close contact, early
      diagnosis and treatment of infected persons as well as decontamination of the
      involved environment play an essential role in controlling outbreaks in
      healthcare settings. 

PMID- 24897949
TI  - Ulcerative colitis: current pharmacotherapy and future directions.
AB  - INTRODUCTION: Ulcerative colitis (UC) is a chronic relapsing disease,
      characterised by alternating of acute and remission phases. Although the
      aetiology is unknown, in recent years, there has progressively been greater
      knowledge of the various pathogenetic mechanisms underlying the disease itself.
      Thus, from therapy based on generically anti-inflammatory or immunosuppressive
      agents, treatment is gradually moving towards drugs that selectively block
      specific inflammatory mediators, such as TNF-alpha. AREAS COVERED: This review
      provides the most significant data about the therapeutic role of different drugs
      currently available for the treatment of UC. In addition, the critical
      therapeutic areas on which research could focus in the near future are discussed.
      EXPERT OPINION: UC is a disease affecting young patients, whose quality of life
      may be strongly compromised by the progression of disease. Over time, the disease
      may lead to an impairment of the normal anatomy and physiology of the colon, and
      the cumulative incidence of dysplasia and colorectal cancer increases with the
      time. Thus, the main aims of the near future should be both a better definition
      of patients at risk for a poor clinical course and progression of disease, and
      the development of a much more aggressive treatment for patients with a poor
      prognosis.

PMID- 24897951
TI  - Mechanics and spiral formation in the rat cornea.
AB  - During the maturation of some mammals such as mice and rats, corneal epithelial
      cells tend to develop into patterns such as spirals over time. A better
      understanding of these patterns can help to understand how the organ develops and
      may give insight into some of the diseases affecting corneal development. In this
      paper, a framework for explaining the development of the epithelial cells forming
      spiral patterns due to the effect of tensile and shear strains is proposed. Using
      chimeric animals, made by combining embryonic cells from genetically
      distinguishable strains, we can observe the development of patterns in the
      cornea. Aggregates of cell progeny from one strain or the other called patches
      form as organs and tissue develop. The boundaries of these patches are fitted
      with logarithmic spirals on confocal images of adult rat corneas. To compare with
      observed patterns, we develop a three-dimensional large strain finite element
      model for the rat cornea under intraocular pressure to examine the strain
      distribution on the cornea surface. The model includes the effects of oriented
      and dispersed fibrils families throughout the cornea and a nearly incompressible
      matrix. Tracing the directions of critical strain vectors on the cornea surface
      leads to spiral-like curves that are compared to the observed logarithmic
      spirals. Good agreement between the observed and numerical curves supports the
      proposed assumption that shear and tensile strains facilitate sliding of
      epithelial cells to develop spiral patterns. 

PMID- 24897952
TI  - Case series of elective instrumented posterior lumbar spinal fusions
      demonstrating a low incidence of venous thromboembolism.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a significant cause of morbidity and
      mortality in orthopaedic surgery. While specific guidelines exist for hip and
      knee arthroplasty, there is wide variation in VTE prophylaxis in complex spinal
      surgery. This study sought to determine the incidence of VTE, and risk factors
      associated with VTE, in patients undergoing elective instrumented posterior
      lumbar spinal fusion. METHODS: In a single-centre case series study, 107
      consecutive patients undergoing elective lumbar spinal fusion were evaluated for
      VTE by lower limb duplex ultrasonography and/or clinical observation, and where
      indicated, computed tomography pulmonary angiogram. The Caprini model for
      thrombosis risk factor assessment was retrospectively applied to grade levels of
      VTE risk, which were compared with overall VTE incidence. RESULTS: All patients
      were operated on a spinal frame and received mechanical prophylaxis
      (thromboembolic deterrent stockings and sequential calf-compression devices).
      Thirty-seven per cent also received chemoprophylaxis with low-molecular-weight
      heparin (LMWH). There was no significant relationship between LMWH use and
      protection from VTE. Risk scores >=3 (high/highest risk categories) were observed
      in 96.2% of patients. Four (3.7%) patients encountered a VTE complication (all
      with no chemoprophylaxis), either deep vein thrombosis (1.9%) or pulmonary
      embolism (1.9%). No patients sustained an epidural haematoma. CONCLUSION:
      Although patients undergoing elective instrumental posterior lumbar spinal fusion
      are at high risk of developing VTE, the actual incidence of VTE in these patients
      is low. Our data support the use of mechanical prophylaxis with thromboembolic
      deterrent stockings and sequential calf-compression devices to prevent VTE in
      these patients.

PMID- 24897953
TI  - Decomposition of educational differences in life expectancy by age and causes of
      death among South Korean adults.
AB  - BACKGROUND: Decomposition of socioeconomic inequalities in life expectancy by
      ages and causes allow us to better understand the nature of socioeconomic
      mortality inequalities and to suggest priority areas for policy and intervention.
      This study aimed to quantify age- and cause-specific contributions to
      socioeconomic differences in life expectancy at age 25 by educational level among
      South Korean adult men and women. METHODS: We used National Death Registration
      records in 2005 (129,940 men and 106,188 women) and national census data in 2005
      (15, 215, 523 men and 16,077,137 women aged 25 and over). Educational attainment
      as the indicator of socioeconomic position was categorized into elementary school
      graduation or less, middle or high school graduation, and college graduation or
      higher. Differences in life expectancy at age 25 by educational level were
      estimated by age- and cause-specific mortality differences using Arriaga's
      decomposition method. RESULTS: Differences in life expectancy at age 25 between
      college or higher education and elementary or less education were 16.23 years in
      men and 7.69 years in women. Young adult groups aged 35-49 in men and aged 25-39
      in women contributed substantially to the differences between college or higher
      education and elementary or less education in life expectancy. Suicide and liver
      disease were the most important causes of death contributing to the differences
      in life expectancy in young adult groups. For older age groups, cerebrovascular
      disease and lung cancer were important to explain educational differential in
      life expectancy at 25-29 between college or higher education and middle or higher
      education. CONCLUSIONS: The contribution of the causes of death to socioeconomic
      inequality in life expectancy at age 25 in South Korea varied by age groups and
      differed by educational comparisons. The age specific contributions for different
      causes of death to life expectancy inequalities by educational attainment should
      be taken into account in establishing effective policy strategies to reduce
      socioeconomic inequalities in life expectancy.

PMID- 24897954
TI  - Tumour budding in head and neck squamous cell carcinoma - a systematic review.
AB  - Tumour budding is a specific type of invasive growth in carcinomas characterized
      by invading single tumour cells or small clusters of tumour cells (<5 cells) at
      the invasive front (IF). It has been documented in numerous publications during
      the past few decades, but its value as a prognostic marker in head and neck
      squamous cell carcinoma (HNSCC) has been analysed only recently. In this review
      we aimed to address the question of whether or not tumour budding has an impact
      upon the progression and prognosis of HNSCC. We systematically reviewed the
      databases of PubMed, Scopus and Web of Science for articles that studied tumour
      budding in squamous cell carcinoma of the head and neck region. The search was
      limited to articles published in the English literature before March 2014. A
      total of 122 hits were retrieved; however, only five reports met the inclusion
      criteria. The findings of these reports suggested a strong association between
      tumour budding and tumour progression, in addition to strong correlation with
      patient prognosis. Standardization of the scoring method and the risk
      stratification cut-off point is necessary before the inclusion of tumour budding
      in pathological reports during daily practice. 

PMID- 24897955
TI  - Emotion-induced blindness reflects competition at early and late processing
      stages: an ERP study.
AB  - Emotion-induced blindness (EIB) refers to impaired awareness of items appearing
      soon after an irrelevant, emotionally arousing stimulus. Superficially, EIB
      appears to be similar to the attentional blink (AB), a failure to report a target
      that closely follows another relevant target. Previous studies of AB using event
      related potentials suggest that the AB results from interference with selection
      (N2 component) and consolidation (P3b component) of the second target into
      working memory. The present study applied a similar analysis to EIB and,
      similarly, found that an irrelevant emotional distractor suppressed the N2 and
      P3b components associated with the following target at short lags. Emotional
      distractors also elicited a positive deflection that appeared to be similar to
      the PD component, which has been associated with attempts to suppress salient,
      irrelevant distractors (Kiss, Grubert, Petersen, & Eimer, 2012; Sawaki, Geng, &
      Luck, 2012; Sawaki & Luck, 2010). These results suggest that irrelevant emotional
      pictures gain access to working memory, even when observers are attempting to
      ignore them and, like the AB, prevent access of a closely following target.

PMID- 24897956
TI  - In vitro thrombolytic activity of purified streptokinase extracted from
      Streptococcus equinus VIT_VB2 isolated from bovine milk.
AB  - Streptokinase (SK) is an extracellular enzyme secreted by various strains of beta
      hemolytic Streptococci. The main focus of the current study is to evaluate the in
      vitro thrombolytic activity of purified SK extracted from Streptococcus equinus
      VIT_VB2 (Accession no. JX406835) isolated from milk sample. The growth rate of S.
      equinus VIT_VB2 strain was studied with pH and biomass content which has positive
      significant effect on enzyme yield. A temperature of 10  degrees C and pH of 6
      was found to be optimum for maximum SK activity. The specific activity of the
      purified SK produced by VIT_VB2 strain was found to be 6,585 IU mg(-1). The
      molecular mass of the enzyme was determined as 47 kDa by SDS-PAGE. In vitro
      thrombolytic activity of purified SK was determined using synthetic chromogenic
      substrate S-2251, the activity of the purified enzyme was found to be 6,330 +/-
      2.2 IU. The purity of SK was compared with standard SK by HPLC. This is the first
      report which reveals the SK activity of S. equinus isolated from milk sample. 

PMID- 24897958
TI  - Micro-effects of smoking in cardiovascular disease aetiology.

PMID- 24897957
TI  - Cannabinoids prevent the effects of a footshock followed by situational reminders
      on emotional processing.
AB  - Posttraumatic stress disorder (PTSD) can develop following exposure to a
      traumatic event. Hence, what we do in the first few hours after trauma exposure
      may alter the trajectory of PTSD. We examined whether cannabinoids can prevent
      the effects of a single footshock followed by situational reminders (SRs) on
      emotional processing. Rats were exposed to a footshock (1.5 mA, 10 s) on day 1
      followed by exposure to SRs of the shock on days 3 and 5. The CB1/2 receptor
      agonist WIN55,212-2 or vehicle were injected intraperitoneally 2 h after the
      shock. After 1 week, PTSD-like symptoms were examined. Exposure to SRs
      exacerbated the effects of the shock as rats exposed to shock and SRs, but not
      shock alone, showed impaired extinction of the traumatic event, impaired
      plasticity in the hippocmapal-accumbens pathway, enhanced latency to startle, and
      altered expression of CB1 receptors (CB1r) and glucocorticoid receptors (GRs) in
      the CA1, basolateral amygdala (BLA) and prefrontal cortex (PFC). WIN55,212-2
      prevented the effects of the shock and SRs on extinction, plasticity, and startle
      response. WIN55,212-2 normalized the shock/SR-induced upregulation in CB1r in the
      PFC, and CA1 and GRs in the CA1, with no effect on BLA downregulation of CB1r and
      GRs. Shock and SRs caused lasting (1 week) alterations in emotional processing
      associated with changes in GR and CB1r expression in brain areas related to PTSD.
      WIN55,212-2 administered after trauma exposure prevented these alterations via
      PFC- and CA1-CB1r and CA1-GRs. 

PMID- 24897959
TI  - Characterization of SET/I2PP2A isoforms in dogs.
AB  - SET is an endogenous protein phosphatase 2A (PP2A) inhibitor and is associated
      with a poor prognosis in human leukemia. Previously, we reported increased SET
      protein levels in canine lymphoma cell lines and the potential therapeutic
      application of SET antagonists in canine lymphoma. Here, we found that canine
      cells express several isoforms of the SET protein. We cloned 4 isoforms of SET,
      named SETalpha, beta, gamma and delta. Genomic BLAST showed that the SET genes
      are located on chromosomes X, 7, 1 and 8, respectively. An immunofluorescent
      study showed nuclear localization of SETalpha and beta, and nuclear and cytosolic
      localization of SETgamma and delta. We confirmed that SETalpha and beta possess
      the ability to associate with PP2A. Our data reveal the existence of unique SET
      isoforms that should be taken into account in SET-targeting drug development
      studies in dogs. 

PMID- 24897961
TI  - Dis/Assembling Schizophrenia on YouTube: Theorizing an Analog Body in a Virtual
      Sphere.
AB  - As visual technologies become increasingly networked online, websites like
      YouTube provide a space to share vlogs (video blogs) online, suggest related
      content for viewers, and help in/form virtual communities, including those of
      mental illness. Within this space, vlogs of schizophrenia and comments generated
      about them by other users can represent transitional, dialogical states of
      illness that speak back to the analog body and affect a body's way of being in
      the world. Moreover, as vlogs create resistance against static definitions of
      schizophrenia, they may foster a creativity, experimentation, and inventiveness
      that transforms understandings of schizophrenia within the sciences and
      humanities. 

PMID- 24897960
TI  - Evaluation of microRNA-10b prognostic significance in a prospective cohort of
      breast cancer patients.
AB  - BACKGROUND: MicroRNA-10b (miR-10b) has a prominent role in regulating tumor
      invasion and metastasis by targeting the HOXD10 transcriptional repressor and has
      been found up-regulated in several tumor types. METHODS: We evaluated the
      expression of miR-10b in paired tumor and normal specimens obtained from a
      prospective cohort of breast cancer patients with at least 36 months follow-up
      enrolled according to the REMARK guidelines (n = 150). RNA quality was measured
      and only samples with RNA Integrity Number (RIN) >=7.0 were analyzed. RESULTS:
      The relative expression of miR-10b in tumor as compared to its normal counterpart
      (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of
      patients with synchronous metastases (n = 11, Median 0.25; IQR 0.11-1.02) as
      compared with patients without metastases (n = 90, Median 0.09; IQR 0.04-0.29) (p
      = 0.028). In the subgroup of patients without synchronous metastases (n = 90),
      higher miR-10b RERs were associated with increased risk of disease progression
      and death in both univariable (HR 1.16, p = 0.021 and HR 1.20, p = 0.015
      respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable
      (HR1.30, p < 0.001, and HR 1.31, p = 0.003 respectively for 0.10 unitary increase
      of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to
      the Nottingham Prognostic Index (NPI) provided an improvement in discrimination
      power and risk reclassification abilities for the clinical outcomes at 36 months.
      Survival C-indices significantly increased from 0.849 to 0.889 (p = 0.009) for OS
      and from 0.735 to 0.767 (p = 0.050) for DFS. CONCLUSIONS: Our results provide
      evidences that the addition of miR-10b RERs to the prognostic factors used in
      clinical routine could improve the prediction abilities for both overall
      mortality and disease progression in breast cancer patients.

PMID- 24897962
TI  - Coping with oral cancer: the impact of health and disease-related personality
      traits.
AB  - PURPOSE: Oral tumours lead to critical reductions in quality of life and well
      being. Coping with illness is a multidimensional construct that is affected by
      various factors, including social structure, social support, locus of control and
      religious considerations. However, the effect of personality on coping with
      illness has hardly been studied. In this context, just one personality model has
      been developed, but this defines personality in very wide dimensions. Therefore,
      this study considered the personality factors related to health and disease and
      aimed to identify potential clinical applications in patients with oral cancer.
      METHODS: We enrolled 104 patients suffering from oral cancer. Participants were
      asked about their personality and illness coping styles using the Freiburg
      Personality Inventory and the Freiburg Questionnaire of Coping with Illness,
      respectively. RESULTS: Regression analyses revealed that specific personality
      structures of the patients determine their way of coping. Patients primarily used
      active and problem-oriented coping styles; spirituality, depressive coping and
      minimization were used less frequently. CONCLUSIONS: The results demonstrate that
      personality affects coping behaviour. When treating patients, both situational
      factors and personality traits affect how patients cope with their disease. We
      note that it is important to give particular attention to patients who use
      depressive coping styles, as these patients are often incapable of coping with
      their diseases without external support.

PMID- 24897964
TI  - Ear, nose and throat manifestations of mucocutaneous Leishmaniasis: a literature
      review.
AB  - Leishmaniasis comprises a group of diseases caused by a protozoan parasite
      belonging to the genus Leishmania and transmitted by the bite of infected female
      sand flies. Leishmaniasis is endemic in 88 countries and causes significant
      morbidity and mortality worldwide. Phenomena such as globalization and human
      migration, as well as the increased volume of international travel have extended
      its prevalence in developed countries. In addition, the incidence of
      leishmaniasis as an opportunistic disease has increased in recent years because
      of the growing number of patients with immune depression secondary to chronic
      illness, neoplasm, transplant and HIV infection, thereby constituting a public
      health problem. In humans, there are three possible clinical syndromes of
      leishmaniasis: cutaneous, mucocutaneous and visceral. Mucocutaneous disease is
      due to extension of local skin disease into the mucosal tissue via direct
      extension, bloodstream or lymphatics. Lesions interest mainly the oral and nasal
      mucosa and occasionally the laryngeal and pharyngeal mucosa. If not recognized
      and adequately treated, MCL may disfigure the patient because of the chronic
      local destruction of tissue of the nose, pharynx and palate. Because of the
      invariable involvement of the areas pertaining otorhinolaryngologists, it is
      important for ENT specialists and family physicians to have awareness of this
      condition and its clinical manifestations, particularly in presence of a history
      positive for travel to endemic areas. If mucocutaneous leishmaniasis is
      suspected, otorhinolaryngologic examination is very helpful in establishing a
      correct diagnosis, preventing inappropriate treatment.

PMID- 24897965
TI  - Contribution to the validation of Italian version of Fear-Avoidance Beliefs
      Questionnaire.
AB  - BACKGROUND AIM: Propose further evidence for reliability and validity of Italian
      translation and adaptation of Fear Avoidance Beliefs Questionnaire, (FABQ)
      originally built-up by Waddel et al. (1993) METHODS: 250 participants, inpatient
      and outpatient, suffering from acute or chronic back-pain have been consecutively
      recruited from various Italian physiotherapy and functional rehabilitation
      centres. All participants were administered FABQ and QUALEFFO, to evaluate if
      avoiding behaviors can provoke disability independently from experimented pain.
      RESULTS: Varimax rotation, point out a 4 factor structure: "Prognosis", "Work as
      cause", "Damage Expectancy", "Physical activity as cause". Statistical analysis
      underlined a good internal consistency. A good criterion validity resulted from
      correlation between FABQ scoring and QUALEFFO. The sample was splitted in
      "avoiders" (A) and "confronters" (C). Group A had no significant correlation
      between FABQ-W score and pain episode lasting, remission interval lasting, back
      pain sick leave; no significant correlation emerged between beliefs and perceived
      pain. In group C a direct relation emerged between duration of sick leave, FABQ-W
      scores and FABQTOT scores, and an association between FABQ scores and reported
      pain. CONCLUSION: Pain-related fear and fear-avoidance beliefs are specific index
      which have to be considered in the first assessment phases, to prevent their
      effect on global functioning and on patients' quality of life. FABQ pointed out
      good reliability and validity propriety in Italian version. FABQ seems to be a
      brilliant instrument for multidisciplinary clinical practice in pain problem
      approach.

PMID- 24897963
TI  - Evaluation of multiplex PCR in first episodes of febrile neutropenia as a tool to
      improve early yeast diagnosis in leukemic/preleukemic patients.
AB  - In febrile neutropenic onco-hematological patients, delayed microbiological
      diagnosis leads to an increase in morbidity and mortality. Identification of the
      microorganism changes antibiotic therapy in more than half of cases; however, in
      only 20-30 % of such cases pathogen isolation is achieved. This study evaluates
      the frequency of fungus infection and its etiology in onco-hematological patients
      with febrile neutropenia utilizing blood cultures and non-commercial multiplex
      polymerase chain reaction (MT-PCR) primers. Fifty-three febrile neutropenia
      episodes in 35 onco-hematological patients were observed, and the results for the
      first unique 30 episodes are presented. Blood cultures were positive for Candida
      tropicalis (one case), gram-positive bacteria (two cases), and gram-negative
      bacteria (four cases), showing a 23.3 % microbiological isolation rate. Multiplex
      PCR pan-fungal sequence was positive in 18 cases (60 %), and further sequencing
      identified fugal pathogens in 11 cases (Candida glabrata and Candida parapsilosis
      being the most common). MT-PCR pan-fungal sequence amplification was detected in
      13 of 16 patients that later received antifungal treatment for clinical reasons
      only, while positivity was found in 5 out of 14 patients that did not receive
      antifungal treatment (p = 0.02). These results show that performing in-house non
      commercial MT-PCR is feasible and may provide additional information about fungal
      infection without the need to wait for culture results. Further research is
      necessary to incorporate this technology into the decision-making process.

PMID- 24897966
TI  - Brittle diabetes: psychopathological aspects.
AB  - BACKGROUND: The term "brittle" is used to described an uncommon subgroup of type
      I diabetics whose lives are disrupted by severe glycaemic instability with
      repeated and prolonged hospitalization. Psychosocial problems are the major
      perceived underlying causes of brittle behaviour. Aim of this study is a
      systematic psychopathological assessment of brittleness using specific parameters
      of general psychopathology and personality traits following the multiaxial format
      (axis I and II) of the current DSM-IV-TR diagnostic criteria for mental
      disorders. METHODS: Patients comprised 21 brittle type I diabetics and a case
      control group of 21 stable diabetics, matched for age, gender, years of
      education, and diabetes duration. General psychopathology and the DSM-IV-TR
      personality traits/disorders were assessed using the Syptom Checklist-90-R (SCL
      90-R) and the Millon Clinical Multiaxial Inventory-III (MCMI-III). RESULTS: The
      comparison for SCL-90-R parameters exclusively revealed higher scores in "Phobic
      Anxiety" subscale in brittle diabetics. No differences in all the other SCL-90-R
      primary symptom dimensions and in the three SCL-90-R global distress indices were
      observed between the two diabetic groups, as well as in the all MCMI-III clinical
      syndrome categories corresponding to DSM-IV-TR specific psychiatric disorders.
      However, brittle patients presented lower scores in MCMI-III compulsive
      personality traits and higher scores in paranoid, schizoid, schizotypal,
      antisocial, borderline, narcissistic, avoidant, dependent, depressive, and
      passive-aggressive personality traits. CONCLUSIONS: In this study, brittle
      diabetics show no differencies in terms of global severity of psychopathological
      distress and axis I specific DSM-IV-TR diagnoses in comparison with non-brittle
      subjects (except for phobic anxiety). Differently, brittle diabetics are
      characterized from less functional and maladaptive personality features and
      suffer more frequently and intensively from specific pathological personality
      traits of all DSM-IV-TR clusters.

PMID- 24897967
TI  - Cochlear effects of intraoperative use of Mesna in cholesteatoma surgery.
AB  - BACKGROUND AND AIM OF THE WORK: Mesna is thiol compound proposed as chemical
      dissector in otolaryngologic surgery. The aim of this study was to address the
      issue of possible ototoxicity from topical administration of MESNA into the
      middle ear during otologic surgery. METHODS: Audiological findings of patients
      (n=55) who underwent canal wall up tympanomastoidectomy with the ancillary use of
      Mesna in 1-year period were retrospectively reviewed. We identified another set
      of 51 patients who had undergone otologic surgery without the use of Mesna to
      serve as a control group. Preoperative and postoperative mean bone conduction
      thresholds were calculated and compared between the two groups for the
      frequencies of 500,1000,2000, and 3000; 4000 and 8000 Hz were further analyzed to
      search for high-frequency sensorineural hearing loss. RESULTS: Fifty-five
      patients were operated on with the ancillary use of Mesna and 51 underwent
      surgery with traditional mechanical dissection alone. When mean preoperative bone
      conduction values were compared with postoperative values, no significant
      differences were found for any of the frequencies tested in both groups.
      Analyzing changes in bone conduction at 4000 and 8000 Hz a slight worsening was
      observed in both groups. CONCLUSIONS: We found no difference in hearing
      thresholds between the treatment and control groups. Thus, the results of this
      study confirmed data obtained in laboratory animal models demonstrating that
      intraoperative use of Mesna in middle ear surgery is safe and does not lead to
      ototoxic effects.

PMID- 24897968
TI  - Periprosthetic fractures of the femur: our experience.
AB  - A frequent problem in Orthopedic surgery is represented by periprosthetic
      fractures in Total Hip Arthroplasty (THA). The incidence of this pathology has
      interested 1,5% in primary THA and till 6-8% in revision prosthesis during last
      10 years. About this contest, the authors performed a study on 24 patients (6
      males; 18 females) surgically treated for periprosthetic femoral fracture at the
      Orthopedic and Traumatologic Clinic, University of Trieste, Italy, in the period
      from January 2006 to December 2011. Periprosthetic fractures were classified
      following guide-lines of the Vancouver Classification System. Even the choice of
      treatment was based on Vancouver Classification System, on patient clinical
      conditions and patients age.

PMID- 24897969
TI  - In vitro protective effect of Celergen, a bioactive marine compound, on
      interleukin-6-related invasiveness of pancreatic cancer.
AB  - The purpose of this study was to assess the effect of Celergen, a marine
      nutraceutical, against tumor cell invasion in human pancreatic cancer cell line
      (PSN-I). High invasive clone (HI) and low invasive clone (LI) were established
      from wild type PSN-l cell line after a repeated invasion assay test. The invasive
      ability of HI cells and the level of IL-6 in the conditioned medium of HI cells
      was significantly higher than that one of LI cells but both these parameters were
      significantly reduced by the addition of Celergen (p<0.01). Exogenous IL-6
      administration induced a dose dependent enhancement of invasive ability in both
      cell populations. Moreover, IL-6 receptor expression was detected in 72% of HI
      cells whereas this occurred only in 37% of LI cells. When co-cultured with
      Celergen this parameter was significantly downregulated in both cellular subsets
      (p<0.05). The addition of conditioned medium derived from HI cells (HCM) and LI
      cells(LCM) enhanced the invasive ability in both cell populations without
      affecting cell proliferation. The effect of HCM on the invasive ability of HI
      cells was partially inhibited by the addition of Celergen (p<0.01). In summary,
      overexpression of IL-6 and its receptor may be one relevant factor contributing
      to the highly invasive characteristic of the pancreatic cancer cell line we used
      while a significantly beneficial modulation was obtained by applying this novel
      marine nutraceutical. This advices to further explore the possibility of marine
      compounds regulation of IL-6 ligand/receptor and other possible invasive factor
      interaction in the therapy of this malignancy while further studies are awaited
      in this setting.

PMID- 24897970
TI  - Necrotizing fasciitis of the neck: considerations about two cases.
AB  - BACKGROUND AND AIM OF THE WORK: Necrotizing fasciitis is a rapidly progressing
      life-threatening infection of the deep fat and fascial layers, which rarely
      occurs in the neck. The aim of the paper is to report the management of this rare
      condition, pointing out the role of multimodality in achieving the cure of the
      patient. METHODS: We report our experience regarding the management of two cases
      of necrotizing fasciitis of the neck successfully treated with surgical and
      medical treatment. DISCUSSION: Early diagnosis of necrotizing fasciitis of the
      neck plays a central role in preventing progression of the disease. Multimodal
      treatment should be mandatory. CONCLUSIONS: Securing of the airway, immediate
      aggressive surgical debridement, and antibacterial agents administration
      represent the effective treatment in preventing progression of the disease.
      Intensive care support should be considered as an integral part of treatment.

PMID- 24897971
TI  - Thirty-year patency of a coronary sequential venous bypass graft.
AB  - BACKGROUND: The optimal conduit of second choice in surgical coronary
      revascularization remains a matter of debate. Radial artery grafts are believed
      to have a better patency rate than the saphenous vein grafts, although no
      conclusive results have been reported. This report describes the late result of a
      coronary revascularization with sequential venous bypass performed 30 years
      earlier. METHODS: An 80-year-old woman was admitted for dyspnoea on exertion and
      recent-onset angina due to severe aortic valve stenosis. Thirty years earlier,
      the patient had undergone revascularization with coronary bypass grafting
      performed using a sequential saphenous vein graft anastomosed on first diagonal
      branch and on left anterior descending coronary artery. Coronary angiography
      showed the occlusion of the native left anterior descending artery and the good
      patency of the previous described sequential vein graft. RESULTS: Surgical
      inspection confirmed the patency and the soft pliability of the venous graft and
      the surgeon decided to do not replace the previous graft with a pedicled LIMA
      (Left Internal Mammary Artery) graft. The patient underwent 21-mm biological
      Edwards Perimount Magna Ease prosthesis implantation. Postoperative course was
      uneventful and the patient was discharged on the seventh day after surgery.
      CONCLUSIONS: This case report demonstrated the potential extreme long-term
      patency of a sequential saphenous vein graft in coronary bypass surgery, raising
      the question if vein grafts should be really considered the conduits of last
      resort for coronary artery bypass surgery. Long-term follow-up of randomized
      trials comparing radial artery versus saphenous vein grafts are warranted in
      order to give conclusive answers to this ongoing debate.

PMID- 24897972
TI  - Pigmented epithelioid melanocytoma: report of a case with favourable outcome
      after a 4-year follow-up period.
AB  - BACKGROUND: Pigmented epitheliod melanocytoma (PEM) is a uncommon melanocytoma
      with unique histopathological features and possibly with a favourable prognosis,
      because, although sentinel lymph-node metastases may occur, in the great majority
      of cases described up to now there is no spread beyond regional lymph-nodes. The
      nature of PEM, its biologic behaviour and its relationships to naevi and
      melanoma, however, remain to be clearly established, and several Authors suggest
      that further cases of PEM with long follow-up should be published, in order to
      better assess the biologic/prognostic characteristics of PEM. METHODS AND
      RESULTS: We report a new case of PEM, dealing with an oval, regularly marginated,
      darkly pigmented, asymptomatic nodule. The dermoscopic pattern showed a
      homogeneous blue-black pigmentation, without any other dermoscopic sign. The
      histopathologic analysis showed both isolated and nested oval melanocytes at the
      junctional level, and a mixture of epitheliod and spindle melanocytes, heavily
      pigmented, together with numerous melanophages in the dermis, with tendency to
      periadnexal distribution; cellular atypia was pronounced, but only occasional
      mitoses were identified in the superficial dermis. After a 4-year follow-up
      period after excision, no persistent lesion or metastases occurred. CONCLUSIONS:
      The present case suggests that PEM has a distinct histopathologic/diagnostic
      identity among melanocytic tumours. Although the up-to-now favourable outcome,
      however, our patient needs a large period of observation, and further studies
      with long follow-up are needed to better define the biologic/prognostic identity
      of PEM.

PMID- 24897973
TI  - Hypereosinophilia in a boy with asthma and Varicella Zoster Virus infection.
AB  - Hypereosinophilia is a rare pediatric condition that could be secondary to
      infections, allergens, immunologic disorders or may be expression of a clonal
      proliferation. We report the case of an asthmatic boy aged 9 years who presented
      hypereosinophilia with spontaneous resolution. He had positive serum IgM
      antibodies to Varicella Zoster Virus while other tests, including genetic ones,
      gave negative results. Our findings suggest that in children with unexplained
      hypereosinophilia Varicella Zoster Virus infection should be investigated. 

PMID- 24897974
TI  - Pulmonary arterial hypertension in childhood: an unsual presentation with
      fibrosing mediastinitis.
AB  - Acquired stenosis of normally connected pulmonary veins is a rare condition in
      children, usually associated with mediastinal processes. It may present later
      with a less specific clinical picture, symptoms and signs mimicking chronic lung
      disease. Fibrosing mediastinitis is a rarer disorder of unknown etiology,
      although several suspected causes such as granulomatous diseases, characterized
      by fibrous tissue proliferation within the mediastinum, leading to respiratory
      and cardiac failure by bronchial obstruction or pulmonary hypertension. 

PMID- 24897975
TI  - Dizziness and syncope in young people: keep your mind open! Case report of the
      challenging differentiation between arrhythmogenic right ventricular
      cardiomyopathy/dysplasia (ARVC/D) and catecholaminergic polymorphic ventricular
      tachycardia (CPVT).
AB  - A paradigmatic case of aborted sudden cardiac death (SCD) in a young man is
      discussed, mirroring the challenge of diagnosing the various conditions
      potentially underlying this dramatic condition. Based on the clinical
      characteristics of our case, presenting some overlapping clinical features common
      to both the diseases, the discussion will be focused on Catecholaminergic
      Polymorphic Ventricular Tachycardia (CPVT) and Arrhythmogenic Right Ventricular
      Cardiomyopathy/Dysplasia (ARVC/D). Epidemiological, genetic, diagnostic and
      therapeutic aspect will be discussed. 

PMID- 24897976
TI  - Dermatologic manifestations and neuropathic symptoms in women with Fabry disease.
AB  - Fabry disease (angiokeratoma corporis diffusum universale) is a rare,
      progressive, X-linked lysosomal storage disease. Deficiency of the alpha
      galactosidase A (alpha-gal A) enzyme leads to accumulation of neutral
      glycosphingolipids within vascular endothelial lysosomes of various organs,
      including skin, kidneys, heart, and brain (1). We herein describe the case of a
      30-year-old female presenting two classic signs of Fabry disease, angiokeratomas
      and episodic acroparesthesias, in the absence of other clinical manifestations.
      An haplotype corresponding to the combination of three different nucleotide
      polymorphic variants (g. 7192-7198del5+ g. 10115A>G + g. 10956 C>T) at the
      heterozygous state, was identified (2).

PMID- 24897977
TI  - A wide skull ostelytic metastasis in advanced breast cancer.
AB  - BACKGROUND: We present a case report of a large and deep osteolytic metastasis
      radiological documented involving the skull in a woman affected by advanced
      breast cancer during endocrine therapy.

PMID- 24897978
TI  - [Rendiconto del Consiglio della Societa di Medicina e Scienze naturali della
      Facolta di Medicina e Chirurgia dell'Universita degli studi di Parma (24 Febbraio
      2014)].

PMID- 24897979
TI  - Antero-posterior lingual sliding retraction system for orthodontic correction of
      hyperdivergent Class II protrusion.
AB  - BACKGROUND: This report introduces a lingual bonded retraction system (Kinematics
      of Lingual Bar on Non-Paralleling Technique, KILBON) for efficient sliding
      mechanics combined with vertical control of the anterior and posterior teeth,
      which is suitable for Class II hyperdivergent patients. METHODS: Design and
      biomechanics of the KILBON System were described. Two adults with hyperdivergent
      class II malocclusion were treated with the KILBON system and temporary skeletal
      anchorage devices (TSADs) on the palate. The first patient was treated with
      conventional KILBON system on the upper arch and detailed with lingual
      appliances. The second patient showed the modified design of the KILBON when
      applied to a low palatal vault. RESULTS: A large amount of intrusion and
      retraction of the anterior teeth and simultaneous intrusion of the posterior
      segment were achieved in short treatment time. Concomitant counterclockwise
      rotation of the mandible improved the esthetic profile. Periodontal support
      without dehiscence or bone loss was confirmed on anterior region in spite of
      large amount of retraction. CONCLUSIONS: This report presented a lingual
      retraction system that provides simple and effective vertical and sagittal
      control of both anterior and posterior teeth. The biomechanics are dependable for
      correcting a dentoalveolar protrusion in a patient with Class II hyperdivergent
      skeletal pattern.

PMID- 24897980
TI  - Characterization of macrophage polarizing cytokines in the aseptic loosening of
      total hip replacements.
AB  - Aseptic loosening of hip replacements is driven by the macrophage reaction to
      wear particles. The extent of particle-induced macrophage activation is dependent
      on the state of macrophage polarization, which is dictated by the local cytokine
      microenvironment. The aim of the study was to characterize cytokine
      microenvironment surrounding failed, loose hip replacements with an emphasis on
      identification of cytokines that regulate macrophage polarization. Using qRT-PCR,
      the expression of interferon gamma (IFN-gamma), interleukin-4 (IL-4), granulocyte
      macrophage colony-stimulating factor (GM-CSF), IL-13, and IL-17A was low and
      similar to the expression in control synovial tissues of patients undergoing
      primary hip replacement. Using immunostaining, no definite source of IFN-gamma or
      IL-4 could be identified. IL-17A positive cells, identified as mast cells by
      double staining, were detected but their number was significantly reduced in
      interface tissues compared to the controls. Significant up-regulation of IL-10, M
      CSF, IL-8, CCL2-4, CXCL9-10, CCL22, TRAP, cathepsin K, and down regulation of OPG
      was seen in the interface tissues, while expression of TNF-alpha, IL-1beta, and
      CD206 were similar between the conditions. It is concluded that at the time of
      the revision surgery the peri-implant macrophage phenotype has both M1 and M2
      characteristics and that the phenotype is regulated by other local and systemic
      factors than traditional macrophage polarizing cytokines.

PMID- 24897981
TI  - Tobacco smoking.
AB  - Worldwide, 22% of adults aged >=15 years currently smoke tobacco. Up to half of
      current smokers will eventually die of a tobacco-related disease, and smoking is
      the leading cause of ill health, drug-related death and hospital separations in
      Australia. 

PMID- 24897982
TI  - Tobacco smoking: options for helping smokers to quit.
AB  - BACKGROUND: Although great progress has been made on tobacco control, smoking
      remains one of the most important causes of preventable disease and death in the
      Australian population. The general practice team has much to offer in helping
      smokers to quit. OBJECTIVE: This article provides practical advice on structuring
      smoking cessation support in primary care using the 5As (Ask, Assess, Advise,
      Assist and Arrange follow-up) framework. Up-to-date information on
      pharmacotherapy and issues for special groups are also covered. DISCUSSION: The
      chances of successful quitting are maximised if the patient receives behavioural
      support combined with drug treatment, if nicotine-dependent. Special groups
      needing support include Aboriginal and Torres Strait Islander peoples, people
      with mental illness and pregnant women.

PMID- 24897983
TI  - Alcohol: prevention, policy and primary care responses.
AB  - BACKGROUND: Alcohol is Australia's most socially acceptable legal drug; however
      alcohol-related harms have increased significantly over time. Encouraging safer
      levels of alcohol consumption should be a national health priority and a key
      focus for health practitioners. OBJECTIVE: The purpose of this paper is to
      discuss some of the reasons that alcohol is such a popular and valued commodity
      in Australia, as well as some of the common problems caused by alcohol. We
      outline the most effective policy and treatment approaches to reduce alcohol
      consumption and related harms. DISCUSSION: Research evidence suggests that the
      most effective policies for reducing alcohol consumption and related harms are
      those focused on restricting its availability and accessibility; however, such
      strategies are often not implemented or enforced for political and economic
      reasons. Undertaking screening and brief intervention are effective ways of
      addressing problematic alcohol consumption within primary care and can be further
      supported through promoting community-organised periods of abstinence.

PMID- 24897984
TI  - Problem gambling.
AB  - BACKGROUND: Problem gambling is an increasingly common problem in Australia.
      General practitioners (GPs) have an important role in ensuring that problem
      gambling is detected and treated. OBJECTIVE: We review the clinical issues
      associated with the detection and treatment of problem gambling. DISCUSSION: At
      any one time 1% of the adult Australian population satisfy the clinical criteria
      for problem gambling; a further 4% are at a significant risk. Problem gambling
      frequently presents with other serious mental health conditions. There are
      several guidelines from the National Health and Medical Research Council and
      Australian Medical Association that recommend GP involvement in screening for
      problem gambling. Simple one-item tools are available for that purpose. GP
      screening and referral for problem gambling addresses the currently very low
      rates of treatment. Effective and durable psychological treatments are available
      for the treatment of problem gambling including cognitive behaviour therapy and
      motivational interviewing.

PMID- 24897985
TI  - Risk assessment and initial management of suicidal adolescents.
AB  - BACKGROUND: Adolescents at risk of suicide present a particularly difficult
      management challenge for all clinicians involved in their care. Adolescents have
      more suicidal thoughts and behaviours than adults. Management of adolescents at
      risk of suicide has specific challenges, which are different from those for
      suicidal adults. OBJECTIVE: To provide a review of the relevant clinical factors
      in the assessment of a suicidal adolescent. To provide the general practitioner
      with practical advice for the assessment of a suicidal adolescent, based on the
      international literature. DISCUSSION: This article summarises the demographic,
      clinical, family and environmental and psychological factors associated with
      adolescent suicide risk. Steps towards the management of suicidal adolescents are
      presented and include risk assessment and safety planning.

PMID- 24897986
TI  - Polymyalgia rheumatica: clinical update.
AB  - BACKGROUND: Polymyalgia rheumatica is a relatively common inflammatory rheumatic
      disease. There are no validated international guidelines available for the
      diagnosis and treatment of PMR; however, diagnostic and classification criteria
      are currently being developed. OBJECTIVE: The aim of this article is to summarise
      the main management options suggested by American College of Rheumatology and
      discusses the role of the general practitioner in the diagnosis and early
      management of PMR. DISCUSSION: Diagnosis is made on the basis of a combination of
      clinical and laboratory findings. Patients typically present with shoulder and
      hip girdle pain with pronounced stiffness. Inflammatory markers are usually
      elevated and an ultrasound and MRI of the shoulder and hip can be done to
      localise inflamed tissues. Response to steroids should not be used as a defining
      feature of PMR but treatment with low dose prednisone should be considered. PMR
      has an excellent prognosis if diagnosis is prompt and therapy adequate.

PMID- 24897987
TI  - Are we there yet? Travel vaccinations for Australian children.
AB  - BACKGROUND: Australians travel overseas frequently and general practitioners
      (GPs) are often asked to provide detailed advice on travel vaccinations for
      children. Planning a safe and effective vaccination schedule is dependent on the
      context: where and when the family is travelling, the individual child's medical
      needs and past vaccination history, and if they are visiting family and friends.
      OBJECTIVE: In this paper we provide an overview of the issues to consider when
      vaccinating Australian children for overseas travel. We also list the suite of
      common travel vaccinations and discuss some clinical scenarios that are likely to
      present in Australian general practice. DISCUSSION: Australians love to travel
      overseas and, increasingly, GPs are asked by patients to provide detailed advice
      on travel vaccinations for their children. Decisions regarding vaccinations for
      travelling children can be complex and the advice often differs from that
      provided for adults. Children differ from adults in their vulnerability to
      illnesses and side effects of medications. These differences, as well as their
      status regarding routine childhood vaccinations, all need to be taken into
      account. As with adults, it is important to consider the location and duration of
      travel and time until departure. The age of the child is also important and there
      may be a case for accelerating the routine childhood vaccinations in some
      children. The aim of this paper is to provide a clear and simple outline of the
      vaccination recommendations for children travelling overseas from Australia.

PMID- 24897988
TI  - Allergic dermatitis - Black henna (para-phenylenediamine) use among the East
      African patient population in a general practice setting.
AB  - The use of henna has become a global phenomenon for skin adornment in arms and
      legs. The practice is old and common among communities of East African origin.
      Traditionally, natural henna is used during Eid celebrations, marriage ceremonies
      and other social occasions. However, black henna type with para-phenylenediamine
      (PPD) additive is gaining favour over the natural one due to its effect and ease
      in achieving the desired intensity, longevity and ease of drying. The natural
      henna stains the skin orange to brown and takes an hour to dry while black henna
      is intensely black and dries in minutes. This article describes a case of
      allergic dermatitis due to a black henna use seen in a general practice clinic
      setting and highlights the role of education and counselling of a particular
      community. 

PMID- 24897989
TI  - A masquerade presenting with diplopia.
AB  - BACKGROUND: Diplopia can often be a diagnostic challenge in the general practice
      setting. Differentials broadly include orbital pathology and neuromuscular
      aetiologies. Familiarity with the causes and subsequent investigations can help
      deliver efficient and effective patient care. OBJECTIVE: This article presents a
      unique case to illustrate the diagnostic approach to diplopia and highlights a
      commonly encountered yet often overlooked condition as a differential to diplopia
      in general practice. DISCUSSION: John Murtagh's manual identifies seven
      'masquerades' as diagnoses that are commonly missed in general practice. The
      Murtagh model can be appropriately applied to diplopia in reminding practitioners
      of differentials that can easily slip from one's mind, yet can be diagnosed
      promptly with simple investigations. Atypical presentations of common disease
      processes should always be considered within the diagnostic framework for
      practitioners.

PMID- 24897990
TI  - When lab tests lie ... heterophile antibodies.
AB  - BACKGROUND: Health professionals rely on the accuracy and validity of laboratory
      investigations in managing patients. Occasionally the results of laboratory
      investigations do not correlate with the clinical scenario. Incorrect pathology
      results may lead to unnecessary further investigation, inappropriate therapeutic
      interventions, and considerable anxiety for the patient and doctor. Heterophile
      antibodies are endogenous antibodies in human serum/plasma that may interfere
      with immunoassays resulting in false elevation, or rarely false depression of
      measured values. OBJECTIVE: To alert health professionals to clinical situations
      in which heterophile antibodies may result in misleading results and potentially
      compromise patient care. DISCUSSION: Heterophile antibodies may interfere with a
      number of immunoassays commonly used in clinical practice. Awareness of the
      possibility of interference by heterophile antibodies is important to prevent
      inappropriate management on the basis of erroneous laboratory results.

PMID- 24897991
TI  - 'BeAWARE': supporting non-clinical staff within general practice to promptly
      identify patients presenting with warning signs of heart attack or stroke.
AB  - BACKGROUND: General practice requires systems to deal with patients presenting
      with urgent needs. BeAWARE was developed to support non-clinical staff to
      promptly identify patients with symptoms of heart attack or stroke. METHODS: Data
      were collected from May 2012 to December 2012 on participants completing the
      BeAWARE learning module, including pre- and post-assessments on knowledge,
      confidence and intended action. RESULTS: From May 2012 to December 2012, 1865
      participants completed the module. There were significant increases in recall of
      heart attack and stroke symptoms among non-clinical participants, including chest
      tightness (23.4-48.7%, P DISCUSSION: BeAWARE fulfils a practice gap in patient
      safety by improving non-clinical staff's knowledge, confidence and intended
      action in response to patients presenting with heart attack or stroke warning
      signs.

PMID- 24897992
TI  - How do GPs want to learn in the digital era?
AB  - BACKGROUND: Various continuing medical education (CME) options are available for
      general practitioners (GPs). These options differ in their clinical effectiveness
      and GPs' preferences for learning format. We report on a national survey,
      conducted by NPS MedicineWise, identifying Australian GPs' preferences for CME.
      METHODS: A stratified random sample of 2500 GPs in Australia participated in the
      survey in 2012. Reponses to the questions on GPs' preferences for CME activities
      and motivation for choice were analysed. RESULTS: Most GPs (95%) preferred
      learning in a group rather than on their own. Specifically, 83% preferred face-to
      face lecture-based formats; 70% preferred interactive group discussions; 66%
      preferred one-to-one learning with an expert; and 55% preferred online self
      education. Relevance to clinical practice was the key motivation for
      participation (80%). DISCUSSION: Although GPs are increasingly using online
      learning, conventional face-to-face activities with peers and experts remain
      popular. Lecture-based CME continues to be preferred, despite evidence suggesting
      other modalities may be more effective. CME activities delivered through a
      combination of methods are likely to appeal to the wide range of GP preferences
      while optimising clinical outcomes.

PMID- 24897993
TI  - 'Your lack of organisation doesn't constitute our emergency' - repeat
      prescription management in general practice.
AB  - BACKGROUND: The importance of quality and safety in repeat prescribing is well
      documented, but few studies have examined how practices manage urgent requests
      for repeat prescriptions and why patients require them urgently. METHODS: Twenty
      practice staff (receptionists, practice managers, general practitioners, practice
      nurse) from 10 general practices participated in semi-structured interviews,
      which were audio-recorded, transcribed and analysed thematically. RESULTS:
      Requests for same-day appointments for patients needing repeat prescriptions
      emerged as problematic for most clinics in our study. Reasons included
      convenience, lost prescriptions and running out of medication. Clinics gave
      patients appointments, left prescriptions for collection at reception or ran
      prescription clinics. A need emerged for GPs to support individual clinic policy
      on repeat prescriptions. DISCUSSION: Many urgent requests for repeat
      prescriptions are avoidable. Improvements are needed in the way repeat
      prescriptions are managed, pointing to a closer examination of general practice
      systems, the role of practice staff, pharmacists and patients.

PMID- 24897994
TI  - Reduced lifespan and increased ageing driven by genetic drift in small
      populations.
AB  - Explaining the strong variation in lifespan among organisms remains a major
      challenge in evolutionary biology. Whereas previous work has concentrated mainly
      on differences in selection regimes and selection pressures, we hypothesize that
      differences in genetic drift may explain some of this variation. We develop a
      model to formalize this idea and show that the strong positive relationship
      between lifespan and genetic diversity predicted by this model indeed exists
      among populations of Daphnia magna, and that ageing is accelerated in small
      populations. Additional results suggest that this is due to increased drift in
      small populations rather than adaptation to environments favoring faster life
      histories. First, the correlation between genetic diversity and lifespan remains
      significant after statistical correction for potential environmental covariates.
      Second, no trade-offs are observed; rather, all investigated traits show clear
      signs of increased genetic load in the small populations. Third, hybrid vigor
      with respect to lifespan is observed in crosses between small but not between
      large populations. Together, these results suggest that the evolution of lifespan
      and ageing can be strongly affected by genetic drift, especially in small
      populations, and that variation in lifespan and ageing may often be nonadaptive,
      due to a strong contribution from mutation accumulation.

PMID- 24897995
TI  - The clinical management of hepatocellular carcinoma in the United States, Europe,
      and Asia: a comprehensive and evidence-based comparison and review.
AB  - Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver,
      represents 1 of the leading causes of cancer deaths in the world with an
      estimated 21,670 deaths in the United States in 2013. In contrast to other
      malignancies, there is an array of treatment options for HCC involving several
      specialties in the multidisciplinary care of the patient. Consequently, vast
      heterogeneity in management tendencies has been observed. The objective of this
      report was to review and compare guidelines on the management of HCC from the
      United States (National Comprehensive Cancer Network), Europe (European
      Association for the Study of the Liver-European Organization for Research and
      Treatment of Cancer), and Asia (consensus statement from the 2009 Asian Oncology
      Summit). By and large, all 3 guidelines are similar, with some variance in
      surveillance and treatment allocation recommendations because of regional
      differences in disease and other variables (diagnosis, staging systems) secondary
      to the lack of a concrete, high level of evidence. In contrast to other cancers,
      the geographic differences in tumor biology and resources make it impractical to
      have a globally universal guideline for all patients with HCC. Recommendations
      from the 3 groups are influenced by geographic differences in the prevalence and
      biology of the disease (ie, areas of increased hepatitis B prevalence) and
      available resources (organ availability for transplantation, finances, and
      accessibility to treatment). It is important for both physicians and policy
      makers to include these considerations when treating patients with HCC as well
      when structuring policies and guidelines.

PMID- 24897996
TI  - Structure-properties relationship of carbazole and fluorene hybrid trimers:
      experimental and theoretical approaches.
AB  - Synthesis and properties of fluorene and carbazole derivatives having three
      electrophores per molecule with different architectures are reported. The
      synthesized compounds possess high thermal stabilities with 5% weight loss
      temperatures exceeding 350  degrees C. They form glasses with glass transition
      temperatures ranging from 60 to 68  degrees C. Cyclovoltammetric experiments
      revealed the high electrochemical stability of the fluorene trimer. In contrast,
      2- and 2,7-fluorenyl substituted carbazole derivatives show irreversible
      oxidation in the CV experiments. The electron photoemission spectra of the films
      of the synthesized compounds revealed ionization potentials of 5.65-5.89 eV. Hole
      drift mobilities in the amorphous layers of the synthesized compounds reach 10(
      2) cm(2) V(-1) s(-1) at high electric fields, as established by a xerographic
      time-of-flight technique. DFT calculations show that HOMO and LUMO orbitals of
      the compounds are very similar in energy and shape. The similar hole mobilities
      observed for the three compounds are discussed in the frame of the Marcus theory.
      An important influence of the alkyl groups on the ionization potentials and on
      the hole mobilities was also observed and its origin is discussed. 

PMID- 24897997
TI  - Transient transfection of CHO cells using linear polyethylenimine is a simple and
      effective means of producing rainbow trout recombinant IFN-gamma protein.
AB  - A practical method was developed for the transient transfection of Chinese
      hamster ovary (CHO) cells with 25 kDa linear polyethylenimine (PEI) then optimal
      culture conditions determined for the production of rainbow trout (Oncorhynchus
      mykiss) IFN-gamma recombinant protein. We found that culture temperature had a
      significant impact upon recombinant protein yield, with best results being
      obtained at 32  degrees C. However the amount of serum added to the culture
      medium had no effect upon recombinant IFN-gamma (rIFN-gamma) production. In this
      study maximal rIFN-gamma yields and minimal PEI toxicity were achieved using a
      DNA/PEI ratio of 1:8, where the amount of PEI did not exceed 10 ug per 5 ml of
      RPMI1640 culture medium, with cells subsequently cultured at 32  degrees C for 7
      days. Thus, linear PEI is a technically simple and cost-efficient method for the
      transient transfection of CHO cells and is compatible with serum-free operations.

PMID- 24897998
TI  - Recombinant IFN-alpha2a-NGR exhibits higher inhibitory function on tumor
      neovessels formation compared with IFN-alpha2a in vivo and in vitro.
AB  - We previously reported that NGR-fused IFN-alpha2a (IFN-alpha2a-NGR) exhibited
      similar biological activities with native IFN-alpha2a and was well-tolerated in
      mice, rats and monkeys. In the current study, we evaluated the mechanisms of this
      fusion protein on angiogenesis and tumor formation. Our data indicated that IFN
      alpha2a-NGR has the ability to target tumor blood vessels while preserving the
      original function of native IFN-alpha2a. IFN-alpha2a-NGR was found to be
      concentrated in the tumor tissues, particularly around the vessel areas. In
      contrast to IFN-alpha2a, IFN-alpha2a-NGR significantly decreased microvessel
      density and increased the apoptosis of vascular endothelial cells. IFN-alpha2a
      NGR also decreased the expression of VEGF and bFGF in tumor cells. Significant
      inhibition of invasion, migration, tube formation and induction of apoptosis of
      endothelial cells were observed in IFN-alpha2a-NGR-treated group. In conclusion,
      results from in vitro and in vivo experiments indicate that IFN-alpha2a-NGR is a
      promising anti-angiogenic agent with greater therapeutic efficacy than IFN
      alpha2a. 

PMID- 24897999
TI  - Plastic induction of CD133AC133-positive cells in the microenvironment of
      glioblastoma spheroids.
AB  - Recent studies showed that the stemness of cancer stem cells is maintained under
      a hypoxic microenvironment. However, the relationship of the hypoxic
      microenvironment in a three-dimensional cell mass and the induction of cancer
      stem cell-like phenotype is not well known. We examined the relationship between
      CD133 expression and the hypoxic microenvironment using glioblastoma spheroids
      formed with the T98G cell line. CD133(AC133)- and HIF-1alpha-positive cells were
      observed in the marginal region of the central hypoxic area positive for HIF
      1alpha 10 days after plating T98G cells. CD133(AC133)-positive cells were
      positive for nestin. Quantitative PCR analysis showed that the CD133 expression
      level is not different in spheroids during the tested period after spheroid
      formation, indicating that post-translational regulation of the CD133 protein
      mediates positivity to CD133(AC133). When spheroids were trypsinized and the
      dissociated cells were cultured under the adherent monolayer conditions, the
      CD133(AC133)-positive cells gradually disappeared. These results show that
      CD133(AC133)-positive cells, which may incline toward undifferentiated cells
      because of nestin positivity, are plastically induced under the different culture
      conditions, spheroid and monolayer. In this plasticity, HIF-1alpha is involved in
      the induction and maintenance of CD133(AC133)-positive cells. Spheroids as an in
      vitro tumor model are useful to study the dynamic changes in the tumor cell
      phenotype in the different cell microenvironments.

PMID- 24898001
TI  - Studying the Therapeutic Process by Observing Clinicians' In-Session Behaviour.
AB  - This paper presents a further step in the use and validation of a systematic,
      functional-analytic method of describing psychologists' verbal behaviour during
      therapy. We observed recordings from 92 clinical sessions of 19 adults (14 women
      and 5 men of Caucasian origin, with ages ranging from 19 to 51 years) treated by
      nine cognitive-behavioural therapists (eight women and one man, Caucasian as
      well, with ages ranging from 25 to 48 years). The therapists' verbal behaviour
      was codified and then classified according to its possible functionality. A
      cluster analysis of the data, followed by a discriminant analysis, showed that
      the therapists' verbal behaviour tended to aggregate around four types of session
      differentiated by their clinical objective (assessment, explanation, treatment
      and consolidation). These results confirm the validity of our method and enable
      us to further describe clinical phenomena by distinguishing psychologists'
      classes of clinically relevant activities. Specific learning mechanisms may be
      responsible for clinical change within each class. These issues should be
      analysed more closely when explaining therapeutic phenomena and when developing
      more effective forms of clinical intervention. KEY PRACTITIONER MESSAGE: We
      described therapists' verbal behaviour in a focused fashion so as to develop new
      research methods that evaluate psychological work moment by moment. We performed
      a cluster analysis in order to evaluate how the therapists' verbal behaviour was
      distributed throughout the intervention. A discriminant analysis gave us further
      information about the statistical significance and possible nature of the
      clusters we observed. The therapists' verbal behaviour depended on current
      clinical objectives and could be classified into four classes of clinically
      relevant activities: evaluation, explanation, treatment and consolidation. Some
      of the therapist's verbalizations were more important than others when carrying
      out these clinically relevant activities. The distribution of the therapists'
      verbal behaviour across classes may provide us with clues regarding the
      functionality of their in-session verbal behaviour.

PMID- 24898000
TI  - Hybrid multiphoton volumetric functional imaging of large-scale bioengineered
      neuronal networks.
AB  - Planar neural networks and interfaces serve as versatile in vitro models of
      central nervous system physiology, but adaptations of related methods to three
      dimensions (3D) have met with limited success. Here, we demonstrate for the first
      time volumetric functional imaging in a bioengineered neural tissue growing in a
      transparent hydrogel with cortical cellular and synaptic densities, by
      introducing complementary new developments in nonlinear microscopy and neural
      tissue engineering. Our system uses a novel hybrid multiphoton microscope design
      combining a 3D scanning-line temporal-focusing subsystem and a conventional laser
      scanning multiphoton microscope to provide functional and structural volumetric
      imaging capabilities: dense microscopic 3D sampling at tens of volumes per second
      of structures with mm-scale dimensions containing a network of over 1,000
      developing cells with complex spontaneous activity patterns. These developments
      open new opportunities for large-scale neuronal interfacing and for applications
      of 3D engineered networks ranging from basic neuroscience to the screening of
      neuroactive substances. 

PMID- 24898002
TI  - Nuclear expression of p53 in mature tumor endothelium of retinoblastoma.
AB  - The present study aimed to investigate the p53 expression pattern in tumor cells
      and in mature tumor vascular endothelium of retinoblastoma. Nuclear p53
      accumulation was observed in most of the tumor cells in both the human and
      orthotopic retinoblastoma animal models using SNUOT-Rb1 and Y79 cells. In the
      orthotopic animal model, some of the tumor vascular endothelium also demonstrated
      nuclear p53 immunoreactivity, and the ratio of p53 positivity among the total
      mature tumor vascular endothelium was slightly higher in the Y79 cell model when
      compared with the SNUOT-Rb1 cell model. In addition, in the human retinoblastoma
      specimens, 32.9% of the tumor vascular endothelium showed p53 nuclear staining.
      In conclusion, some of the mature tumor vascular endothelium in both the human
      and orthotopic models of retinoblastoma share the same cytogenetic abnormality
      (an abnormal nuclear accumulation of p53) with retinoblastoma cells.

PMID- 24898003
TI  - Prevalence of food allergen-free diets in school canteens in Hortaleza district,
      Madrid.

PMID- 24898005
TI  - Sufficiency of diffusion tensor in characterizing the diffusion MRI signal to
      leading order in diffusion weighting.

PMID- 24898004
TI  - Gating-pore currents demonstrate selective and specific modulation of individual
      sodium channel voltage-sensors by biological toxins.
AB  - Voltage-gated sodium channels are critical determinants of nerve and muscle
      excitability. Although numerous toxins and small molecules target sodium
      channels, identifying the mechanisms of action is challenging. Here we used
      gating-pore currents selectively generated in each of the voltage-sensors from
      the four alpha-subunit domains (DI-DIV) to monitor the activity of individual
      voltage-sensors and to investigate the molecular determinants of sodium channel
      pharmacology. The tarantula toxin huwentoxin-IV (HWTX-IV), which inhibits sodium
      channel current, exclusively enhanced inward gating-pore currents through the DII
      voltage-sensor. By contrast, the tarantula toxin ProTx-II, which also inhibits
      sodium channel currents, altered the gating-pore currents in multiple voltage
      sensors in a complex manner. Thus, whereas HWTX-IV inhibits central-pore currents
      by selectively trapping the DII voltage-sensor in the resting configuration,
      ProTx-II seems to inhibit central-pore currents by differentially altering the
      configuration of multiple voltage-sensors. The sea anemone toxin anthopleurin B,
      which impairs open-channel inactivation, exclusively enhanced inward gating-pore
      currents through the DIV voltage-sensor. This indicates that trapping the DIV
      voltage-sensor in the resting configuration selectively impairs open-channel
      inactivation. Furthermore, these data indicate that although activation of all
      four voltage-sensors is not required for central-pore current generation,
      activation of the DII voltage-sensor is crucial. Overall, our data demonstrate
      that gating-pore currents can determine the mechanism of action for sodium
      channel gating modifiers with high precision. We propose this approach could be
      adapted to identify the molecular mechanisms of action for gating modifiers of
      various voltage-gated ion channels. 

PMID- 24898007
TI  - Group-effort applied research: expanding opportunities for undergraduate research
      through original, class-based research projects.
AB  - Undergraduate research clearly enriches the educational development of
      participating students, but these experiences are limited by the inherent
      inefficiency of the standard one student-one mentor model for undergraduate
      research. Group-effort applied research (GEAR) was developed as a strategy to
      provide substantial numbers of undergraduates with meaningful research
      experiences. The GEAR curriculum delivers concept-driven lecture material and
      provides hands-on training in the context of an active research project from the
      instructor's laboratory. Because GEAR is structured as a class, participating
      students benefit from intensive, supervised research training that involves a
      built-in network of peer support and abundant contact with faculty mentors. The
      class format also ensures a relatively standardized and consistent research
      experience. Furthermore, meaningful progress toward a research objective can be
      achieved more readily with GEAR than with the traditional one student-one mentor
      model of undergraduate research because sporadic mistakes by individuals in the
      class are overshadowed by the successes of the group as a whole. Three separate
      GEAR classes involving three distinct research projects have been offered to
      date. In this article, we provide an overview of the GEAR format and review some
      of the recurring themes for GEAR instruction. We propose GEAR can serve as a
      template to expand student opportunities for life science research without
      sacrificing the quality of the mentored research experience.

PMID- 24898006
TI  - Cilia and polycystic kidney disease, kith and kin.
AB  - In the past decade, cilia have been found to play important roles in renal
      cystogenesis. Many genes, such as PKD1 and PKD2 which, when mutated, cause
      autosomal dominant polycystic kidney disease (ADPKD), have been found to localize
      to primary cilia. The cilium functions as a sensor to transmit extracellular
      signals into the cell. Abnormal cilia structure and function are associated with
      the development of polyscystic kidney disease (PKD). Cilia assembly includes
      centriole migration to the apical surface of the cell, ciliary vesicle docking
      and fusion with the cell membrane at the intended site of cilium outgrowth, and
      microtubule growth from the basal body. This review summarizes the most recent
      advances in cilia and PKD research, with special emphasis on the mechanisms of
      cytoplasmic and intraciliary protein transport during ciliogenesis.

PMID- 24898008
TI  - Limited-angle tomography for analyzer-based phase-contrast x-ray imaging.
AB  - Multiple-image radiography (MIR) is an analyzer-based phase-contrast x-ray
      imaging method, which is emerging as a potential alternative to conventional
      radiography. MIR simultaneously generates three planar parametric images
      containing information about scattering, refraction and attenuation properties of
      the object. The MIR planar images are linear tomographic projections of the
      corresponding object properties, which allows reconstruction of volumetric images
      using computed tomography (CT) methods. However, when acquiring a full range of
      linear projections around the tissue of interest is not feasible or the scanning
      time is limited, limited-angle tomography techniques can be used to reconstruct
      these volumetric images near the central plane, which is the plane that contains
      the pivot point of the tomographic movement. In this work, we use computer
      simulations to explore the applicability of limited-angle tomography to MIR. We
      also investigate the accuracy of reconstructions as a function of number of
      tomographic angles for a fixed total radiation exposure. We use this function to
      find an optimal range of angles over which data should be acquired for limited
      angle tomography MIR (LAT-MIR). Next, we apply the LAT-MIR technique to
      experimentally acquired MIR projections obtained in a cadaveric human thumb
      study. We compare the reconstructed slices near the central plane to the same
      slices reconstructed by CT-MIR using the full angular view around the object.
      Finally, we perform a task-based evaluation of LAT-MIR performance for different
      numbers of angular views, and use template matching to detect cartilage in the
      refraction image near the central plane. We use the signal-to-noise ratio of this
      test as the detectability metric to investigate an optimum range of tomographic
      angles for detecting soft tissues in LAT-MIR. Both results show that there is an
      optimum range of angular view for data acquisition where LAT-MIR yields the best
      performance, comparable to CT-MIR only if one considers volumetric images near
      the central plane and not the whole volume. 

PMID- 24898009
TI  - Iron oxide superparamagnetic nanoparticles conjugated with a conformationally
      blocked alpha-Tn antigen mimetic for macrophage activation.
AB  - Among new therapies to fight tumors, immunotherapy is still one of the most
      promising and intriguing. Thanks to the ongoing structural elucidation of several
      tumor antigens and the development of innovative antigen carriers, immunotherapy
      is in constant evolution and it is largely used either alone or in synergy with
      chemotherapy/radiotherapy. With the aim to develop fully synthetic
      immunostimulants we have recently developed a mimetic of the alpha-Tn mucin
      antigen, a relevant tumor antigen. The (4)C1 blocked mimetic 1, unique example of
      an alpha-Tn mimetic antigen, was functionalized with an omega-phosphonate linker
      and used to decorate iron oxide superparamagnetic nanoparticles (MNPs), employed
      as multivalent carriers. MNPs, largely exploited for supporting and carrying
      biomolecules, like antibodies, drugs or antigens, consent to combine in the same
      nanometric system the main features of an inorganic magnetic core with a
      bioactive organic coating. The superparamagnetic glyconanoparticles obtained,
      named GMNPs, are indeed biocompatible and immunoactive, and they preserve
      suitable characteristics for use as heat mediators in the magnetic fluid
      hyperthermia (MFH) treatment of tumors. All together these properties make GMNPs
      attracting devices for innovative tumor treatment.

PMID- 24898010
TI  - Photodynamic therapy for recurrent respiratory papillomatosis.
AB  - BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a benign condition of
      the mucosa of the upper aerodigestive tract. It is characterised by recurrent
      papillomatous lesions and is associated with human papillomavirus (HPV). Frequent
      recurrence and rapid papilloma growth are common and in part responsible for the
      onset of potentially life-threatening symptoms. Most patients afflicted by the
      condition will require repeated surgical treatments to maintain their airway, and
      these may result in scarring and voice problems. Photodynamic therapy introduces
      a light-sensitising agent, which is administered either orally or by injection.
      This substance (called a photo-sensitiser) is selectively retained in
      hyperplastic and neoplastic tissue, including papilloma. It is then activated by
      light of a specific wavelength and may be used as a sole or adjuvant treatment
      for RRP. OBJECTIVES: To assess the effects of photodynamic therapy in the
      management of recurrent respiratory papillomatosis (RRP) in children and adults.
      SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group
      Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL);
      PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and
      additional sources for published and unpublished trials. The date of the search
      was 27 January 2014. SELECTION CRITERIA: Randomised controlled trials utilising
      photodynamic therapy as sole or adjuvant therapy in participants of any age with
      proven RRP versus control intervention. Primary outcome measures were symptom
      improvement (respiratory distress/dyspnoea and voice quality), quality of life
      improvement and recurrence-free interval. Secondary outcomes included reduction
      in the frequency of surgical intervention, reduction in disease volume and
      adverse effects of treatment.   DATA COLLECTION AND ANALYSIS: We used the
      standard methodological procedures expected by The Cochrane Collaboration. Meta
      analysis was not possible and results are presented descriptively. MAIN RESULTS:
      We included one trial with a total of 23 participants. This study was at high
      risk of bias. None of our primary outcomes and only one of our secondary outcomes
      (reduction in volume of disease, assessed endoscopically) was measured in the
      study. There was no significant difference between the groups (very low-quality
      evidence). Adverse effects reported included airway swelling requiring intubation
      in a child with severe RRP a few hours after photodynamic therapy. AUTHORS'
      CONCLUSIONS: There is insufficient evidence from high-quality randomised
      controlled trials to determine whether photodynamic therapy alters the course of
      disease or provides an added benefit to surgery in patients with recurrent
      respiratory papillomatosis. Multicentre randomised controlled trials with
      appropriate sample sizes and long-term follow-up are required to evaluate whether
      photodynamic therapy is of benefit. Outcomes such as improvement in symptoms
      (respiratory function and voice quality) and quality of life should be measured
      in future trials.

PMID- 24898011
TI  - Ultrastructural changes associated with the induction of premature chromosome
      condensation in Vicia faba root meristem cells.
AB  - KEY MESSAGE: PCC induction is regulated by several signaling pathways, and all
      observed effects associated with PCC induction are strongly dependent on the
      mechanism of action of each PCC inducer used. Electron microscopic observations
      of cells with symptoms of premature chromosome condensation (PCC) showed that the
      interphase chromatin and mitotic chromosomes differed with respect to a chemical
      compound inducing PCC. Induction of this process under the influence of
      hydroxyurea and caffeine as well as hydroxyurea and sodium metavanadate led to a
      slight decrease in interphase chromatin condensation and the formation of
      chromosomes with a considerably loosened structure in comparison with the
      control. Incubation in the mixture of hydroxyurea and 2-aminopurine brought about
      clear chromatin dispersion in interphase and very strong mitotic chromosome
      condensation. Electron microscopic examinations also revealed the characteristic
      features of the structural organization of cytoplasm of Vicia faba root
      meristems, which seemed to be dependent on the type of the PCC inducer used. The
      presence of the following was observed: (i) large plastids filled with starch
      grains (caffeine), (ii) mitochondria and plastids of electron dense matrix with
      dilated invaginations of their internal membranes (2-aminopurine), and (iii)
      large mitochondria of electron clear matrix and plastids containing protein
      crystals in their interior (sodium metavanadate). Moreover, since caffeine causes
      either the most effective loosening of chromatin fibrils (within the prematurely
      condensed chromosomes) or induction of starch formation (in the plastids
      surrounding the nuclei), this may be a proof that demonstrates the existence of a
      link between physical accessibility to chromatin and the effectiveness of
      cellular signaling (e.g., phosphothreonine-connected).

PMID- 24898012
TI  - Effect of solubilizing agents on mupirocin loading into and release from
      PEGylated nanoliposomes.
AB  - Mupirocin was identified by quantitative structure property relationship models
      as a good candidate for remote liposomal loading. Mupirocin is an antibiotic that
      is currently restricted to topical administration because of rapid hydrolysis in
      vivo to its inactive metabolite. Formulating mupirocin in PEGylated nanoliposomes
      may potentially expand its use to parenteral administration by protecting it from
      degradation in the circulation and target it (by the enhanced permeability
      effect) to the infected tissue. Mupirocin is slightly soluble in aqueous medium
      and its solubility can be increased using solubilizing agents. The effect of the
      solubilizing agents on mupirocin remote loading was studied when the solubilizing
      agents were added to the drug loading solution. Propylene glycol was found to
      increase mupirocin loading, whereas polyethylene glycol 400 showed no effect.
      Hydroxypropyl-beta-cyclodextrin (HPCD) showed a concentration-dependent effect on
      mupirocin loading; using the optimal HPCD concentration increased loading, but
      higher concentrations inhibited it. The inclusion of HPCD in the liposome aqueous
      phase while forming the liposomes resulted in increased drug loading and
      substantially inhibited drug release in serum.

PMID- 24898013
TI  - Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome: a case with a novel
      p63 mutation associated with abnormal keratohyalin granules.

PMID- 24898015
TI  - Humidifiers: the use of biocides and lung disease.

PMID- 24898014
TI  - Transcriptomics of cryophilic Saccharomyces kudriavzevii reveals the key role of
      gene translation efficiency in cold stress adaptations.
AB  - BACKGROUND: Comparative transcriptomics and functional studies of different
      Saccharomyces species have opened up the possibility of studying and
      understanding new yeast abilities. This is the case of yeast adaptation to
      stress, in particular the cold stress response, which is especially relevant for
      the food industry. Since the species Saccharomyces kudriavzevii is adapted to
      grow at low temperatures, it has been suggested that it contains physiological
      adaptations that allow it to rapidly and efficiently acclimatise after cold
      shock. RESULTS: In this work, we aimed to provide new insights into the molecular
      basis determining this better cold adaptation of S. kudriavzevii strains. To this
      end, we have compared S. cerevisiae and S. kudriavzevii transcriptome after yeast
      adapted to cold shock. The results showed that both yeast mainly activated the
      genes related to translation machinery by comparing 12 degrees C with 28 degrees
      C, but the S. kudriavzevii response was stronger, showing an increased expression
      of dozens of genes involved in protein synthesis. This suggested enhanced
      translation efficiency at low temperatures, which was confirmed when we observed
      increased resistance to translation inhibitor paromomycin. Finally, 35S
      methionine incorporation assays confirmed the increased S. kudriavzevii
      translation rate after cold shock. CONCLUSIONS: This work confirms that S.
      kudriavzevii is able to grow at low temperatures, an interesting ability for
      different industrial applications. We propose that this adaptation is based on
      its enhanced ability to initiate a quick, efficient translation of crucial genes
      in cold adaptation among others, a mechanism that has been suggested for other
      microorganisms.

PMID- 24898016
TI  - Airborne dissemination of transmissible bacterial species in cystic fibrosis.

PMID- 24898017
TI  - Identification of congenital rubella syndrome in Sudan.
AB  - BACKGROUND: Epidemiological data about congenital rubella syndrome (CRS) are
      scarce and rubella vaccine is not yet included in the childhood immunization
      schedule in Sudan. This study aimed to identify and describe CRS cases among
      Sudanese infants with congenital eye or heart defects. METHODS: Between February
      and September 2010, paired oral fluid and dried blood spot samples were collected
      from 98 infants aged up to 12 months. These infants were enrolled during their
      visits to five hospitals in Khartoum, Sudan. Clinical samples were screened for
      rubella IgM and for >= 6 months old infants also for IgG antibodies by ELISA. The
      oral fluid of IgM and/or IgG positive patients was tested for rubella RNA by
      reverse transcriptase PCR. RESULTS: Our findings revealed that two children
      (2.0%) were IgM positive and another five children (5.1%) were positive for IgG
      antibodies. None of the five infants of which enough oral fluid was available for
      RNA investigation was PCR positive. CONCLUSIONS: This study documented the
      presence of CRS in Sudan and highlighted the importance of rubella vaccine
      introduction for preventing future CRS cases in the country.

PMID- 24898018
TI  - Measurement units for antibiotic consumption in outpatients.

PMID- 24898019
TI  - Impact of a computerized decision support system on compliance with guidelines on
      antibiotics prescribed for urinary tract infections in emergency departments: a
      multicentre prospective before-and-after controlled interventional study.
AB  - OBJECTIVES: Urinary tract infections (UTIs) are one of the leading reasons for
      antibiotic prescriptions in emergency departments (EDs), with half of these
      antibiotics being inappropriately prescribed. Our objective was to assess the
      impact of a computerized decision support system (CDSS) on compliance with
      guidelines on empirical antibiotic prescriptions (antibiotic and duration) for
      UTIs in EDs. METHODS: A multicentre prospective before-and-after controlled
      interventional study was conducted from 19 March to 28 October 2012. All adults
      diagnosed with community-acquired UTIs (cystitis, pyelonephritis or prostatitis)
      at three French EDs were included. The antibiotic therapy was considered
      compliant with guidelines if the antibiotic and the duration prescribed were in
      accordance with the national guidelines. Data were collected using electronic
      medical records. Paired tests were used when comparing periods within each ED and
      global analyses used multivariate logistic mixed models. RESULTS: Nine hundred
      and twelve patients were included during the 30 week study period. The CDSS was
      used in 59% of cases (182/307). The CDSS intervention improved the compliance of
      antibiotic prescriptions in only one ED in a bivariate analysis (absolute
      increase +20%, P = 0.007). The choice of the antibiotic was improved in
      multivariate analyses but only when the CDSS was used [OR = 1.94 (95% CI 1.13
      3.32)]. The CDSS also changed the initial diagnosis in 23% of cases, in all three
      EDs. CONCLUSIONS: The CDSS only partially improved compliance with guidelines on
      antibiotic prescriptions in UTIs.

PMID- 24898020
TI  - Isolation of ciprofloxacin-resistant Legionella pneumophila in a patient with
      severe pneumonia.

PMID- 24898021
TI  - Identification of functional parameters for the classification of older female
      fallers and prediction of 'first-time' fallers.
AB  - Falls remain a challenge for ageing societies. Strong evidence indicates that a
      previous fall is the strongest single screening indicator for a subsequent fall
      and the need for assessing fall risk without accounting for fall history is
      therefore imperative. Testing in three functional domains (using a total 92
      measures) were completed in 84 older women (60-85 years of age), including
      muscular control, standing balance, and mean and variability of gait.
      Participants were retrospectively classified as fallers (n = 38) or non-fallers
      (n = 42) and additionally in a prospective manner to identify first-time fallers
      (FTFs) (n = 6) within a 12-month follow-up period. Principal component analysis
      revealed that seven components derived from the 92 functional measures are
      sufficient to depict the spectrum of functional performance. Inclusion of only
      three components, related to mean and temporal variability of walking, allowed
      classification of fallers and non-fallers with a sensitivity and specificity of
      74% and 76%, respectively. Furthermore, the results indicate that FTFs show a
      tendency towards the performance of fallers, even before their first fall occurs.
      This study suggests that temporal variability and mean spatial parameters of gait
      are the only functional components among the 92 measures tested that
      differentiate fallers from non-fallers, and could therefore show efficacy in
      clinical screening programmes for assessing risk of first-time falling. 

PMID- 24898022
TI  - See-saw rocking: an in vitro model for mechanotransduction research.
AB  - In vitro mechanotransduction studies, uncovering the basic science of the
      response of cells to mechanical forces, are essential for progress in tissue
      engineering and its clinical application. Many varying investigations have
      described a multitude of cell responses; however, as the precise nature and
      magnitude of the stresses applied are infrequently reported and rarely validated,
      the experiments are often not comparable, limiting research progress. This paper
      provides physical and biological validation of a widely available fluid
      stimulation device, a see-saw rocker, as an in vitro model for cyclic fluid shear
      stress mechanotransduction. This allows linkage between precisely characterized
      stimuli and cell monolayer response in a convenient six-well plate format. Models
      of one well were discretized and analysed extensively using computational fluid
      dynamics to generate convergent, stable and consistent predictions of the cyclic
      fluid velocity vectors at a rocking frequency of 0.5 Hz, accounting for the free
      surface. Validation was provided by comparison with flow velocities measured
      experimentally using particle image velocimetry. Qualitative flow behaviour was
      matched and quantitative analysis showed agreement at representative locations
      and time points. Maximum shear stress of 0.22 Pa was estimated near the well
      edge, and time-average shear stress ranged between 0.029 and 0.068 Pa. Human
      tenocytes stimulated using the system showed significant increases in collagen
      and GAG secretion at 2 and 7 day time points. This in vitro model for
      mechanotransduction provides a versatile, flexible and inexpensive method for the
      fluid shear stress impact on biological cells to be studied. 

PMID- 24898024
TI  - Reply: Pretreatment Dosimetry in HCC Radioembolization with (90)Y Glass
      Microspheres Cannot Be Invalidated with a Bare Visual Evaluation of (99m)Tc-MAA
      Uptake of Colorectal Metastases Treated with Resin Microspheres.

PMID- 24898023
TI  - Detection of an en masse and reversible B- to A-DNA conformational transition in
      prokaryotes in response to desiccation.
AB  - The role that DNA conformation plays in the biochemistry of cells has been the
      subject of intensive research since DNA polymorphism was discovered. B-DNA has
      long been considered the native form of DNA in cells although alternative
      conformations of DNA are thought to occur transiently and along short tracts.
      Here, we report the first direct observation of a fully reversible en masse
      conformational transition between B- and A-DNA within live bacterial cells using
      Fourier transform infrared (FTIR) spectroscopy. This biospectroscopic technique
      allows for non-invasive and reagent-free examination of the holistic biochemistry
      of samples. For this reason, we have been able to observe the previously unknown
      conformational transition in all four species of bacteria investigated. Detection
      of this transition is evidence of a previously unexplored biological significance
      for A-DNA and highlights the need for new research into the role that A-DNA plays
      as a cellular defence mechanism and in stabilizing the DNA conformation. Such
      studies are pivotal in understanding the role of A-DNA in the evolutionary
      pathway of nucleic acids. Furthermore, this discovery demonstrates the exquisite
      capabilities of FTIR spectroscopy and opens the door for further investigations
      of cell biochemistry with this under-used technique. 

PMID- 24898025
TI  - In vivo assessment and dosimetry of 2 novel PDE10A PET radiotracers in humans:
      18F-MNI-659 and 18F-MNI-654.
AB  - Phosphodiesterase (PDE) 10A is an enzyme involved in the regulation of cyclic
      adenosine monophosphate and cyclic guanosine monophosphate and is highly
      expressed in medium-sized spiny neurons of the striatum, making it an attractive
      target for novel therapies for a variety of neurologic and psychiatric disorders
      that involve striatal function. Potential ligands for PET imaging of PDE10A have
      been reported. Here, we report the first-in-human characterization of 2 new
      PDE10A radioligands, 2-(2-(3-(1-(2-fluoroethyl)-1H-indazol-6-yl)-7-methyl-4-oxo
      3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI
      654) and 2-(2-(3-(4-(2-fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin
      2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI-659), with the goal of
      selecting the best one for use in future studies interrogating pathophysiologic
      changes in neuropsychiatric disorders and aiding pharmaceutical development
      targeting PDE10A. METHODS: Eleven healthy volunteers participated in this study
      ((18)F-MNI-654 test-retest, 2 men; (18)F-MNI-659 test-retest, 4 men and 1 woman;
      (18)F-MNI-659 dosimetry, 2 men and 2 women). Brain PET images were acquired over
      5.5 h for (18)F-MNI-654 and over 3.5 h for (18)F-MNI-659, and pharmacokinetic
      modeling with plasma- and reference-region (cerebellar cortex)-based methods was
      performed. Whole-body PET images were acquired over 6 h for (18)F-MNI-659 and
      radiation dosimetry estimated with OLINDA. RESULTS: Both radiotracers were
      similarly metabolized, with about 20% of intact parent remaining at 120 min after
      injection. PET time-activity data demonstrated that (18)F-MNI-654 kinetics were
      much slower than (18)F-MNI-659 kinetics. For (18)F-MNI-659, there was good
      agreement between the Logan and simplified reference tissue models for
      nondisplaceable binding potential (BPND), supporting noninvasive quantification,
      with test-retest variability less than 10% and intraclass correlation greater
      than 0.9. The (18)F-MNI-659 effective dose was estimated at 0.024 mSv/MBq.
      CONCLUSION: PET imaging in the human brain with 2 novel PDE10A (18)F tracers is
      being reported. Noninvasive quantification of (18)F-MNI-659 with the simplified
      reference tissue model using the cerebellum as a reference is possible. In
      addition, (18)F-MNI-659 kinetics are fast enough for a good estimate of BPND with
      90 min of data, with values around 3.0 in the basal ganglia. Finally, (18)F-MNI
      659 dosimetry is favorable and consistent with values reported for other PET
      radiotracers currently used in humans.

PMID- 24898026
TI  - Comparison of simplified parametric methods for visual interpretation of 11C
      Pittsburgh compound-B PET images.
AB  - This study compared several parametric imaging methods to determine the optimal
      approach for visual assessment of parametric Pittsburgh compound-B ((11)C-PIB)
      PET images to detect cortical amyloid deposition in different memory clinic
      patient groups. METHODS: Dynamic (11)C-PIB scanning of 120 memory clinic patients
      was performed. Parametric nondisplaceable binding potential (BPND) images were
      compared with standardized uptake value (SUV) and SUV ratio images. Images were
      visually assessed by 3 independent readers, and both interreader and intermethod
      agreement was determined. RESULTS: Both 90-min (Fleiss kappa = 0.88) and 60-min
      (Fleiss kappa = 0.89) BPND images showed excellent interreader agreement, whereas
      agreement was good to moderate for SUV ratio images (Fleiss kappa = 0.68) and SUV
      images (Fleiss kappa = 0.59). Intermethod agreement varied substantially between
      readers, although BPND images consistently showed the best performance.
      CONCLUSION: The use of BPND images provided the highest interreader and
      intermethod agreement and is therefore the method of choice for optimal visual
      interpretation of (11)C-PIB PET scans.

PMID- 24898027
TI  - Pretreatment Dosimetry in HCC Radioembolization with (90)Y Glass Microspheres
      Cannot Be Invalidated with a Bare Visual Evaluation of (99m)Tc-MAA Uptake of
      Colorectal Metastases Treated with Resin Microspheres.

PMID- 24898028
TI  - The effect of lifetime cumulative adversity and depressive symptoms on functional
      status.
AB  - OBJECTIVES: The study aimed to examine whether lifetime cumulative adversity
      (LCA) and depressive symptoms moderate time-related trajectories of functional
      status. METHOD: A total of 15,073 older adults (mean age = 63.91 at Wave 1) who
      participated in the first four waves of the Survey of Health, Ageing and
      Retirement in Europe reported on exposure to negative life events, depressive
      symptoms and three measures of functional status-difficulty in performing daily
      and instrumental activities, and functional limitation. RESULTS: Growth-curve
      models showed that time-related increase in disability and functional limitation
      was steeper among those exposed to higher levels of lifetime adversity. Moreover,
      a three-way interaction between time, lifetime adversity, and depressive symptoms
      emerged across measures of functional status, so that when exposure to lifetime
      adversity was accompanied by high level of depressive symptoms, the time-related
      increase in disability and functional limitation was the steepest. DISCUSSION:
      LCA is associated with a hastening of the disablement process, especially under
      conditions of high distress. Although the overall modest effects imply that
      resilience to lifetime adversity is widespread among older adults, prevention and
      intervention programs should consider that distressed older adults previously
      exposed to high levels of lifetime adversity are at risk for more rapid
      impairment in functional status.

PMID- 24898030
TI  - Perceived Age Discrimination as a Mediator of the Association Between Income
      Inequality and Older People's Self-Rated Health in the European Region.
AB  - OBJECTIVES: The relative income hypothesis predicts poorer health in societies
      with greater income inequality. This article examines whether the psychosocial
      factors of perceived age discrimination and (lack of) social capital may help
      explain the adverse effect of inequality on older people's health. METHODS: Self
      rated health, perceived age discrimination, and social capital were assessed in
      the 2008/9 European Social Survey (European Social Survey Round 4 Data, 2008).
      The Gini coefficient was used to represent national inequalities in income in
      each of the 28 European Social Survey countries. Mediation analyses (within a
      multilevel structural equation modeling paradigm) on a subsample of respondents
      over 70 years of age (N = 7,819) were used to examine whether perceived age
      discrimination mediates the negative effect of income inequality on older
      people's self-rated health. RESULTS: Perceived age discrimination fully mediated
      the associations between income inequality and self-rated health. When social
      capital was included into the model, only age discrimination remained a
      significant mediator and predictor of self-rated health. DISCUSSION: Concrete
      instances of age discrimination in unequal societies are an important
      psychosocial stressor for older people. Awareness that the perception of ageism
      can be an important stressor and affect older patient's self-reported health has
      important implications for the way health practitioners understand and treat the
      sources of patient's health problems in later life.

PMID- 24898029
TI  - Changes in support networks in late middle age: the extension of gender and
      educational differences.
AB  - OBJECTIVES: This paper tests whether differences by gender and by educational
      attainment in contact with friends and family and in support expected from
      friends and family narrow or widen in late middle age. METHODS: The data are
      drawn from about 4,800 members of the Wisconsin Longitudinal Survey who answered
      questions about their frequency of contact with social ties and expectations of 3
      kinds of help in both 1993, when they were in their early 50s, and again in 2004.
      RESULTS: Using lagged dependent variable models, we find that between their 50s
      and 60s women's network advantages over men and college graduates' network
      advantages over high school graduates in frequency of social contact widened. The
      same was roughly true as well for expectations of social support, although here
      the divergences depended partly on the type of the support: Women gained relative
      to men in "talk" support and in help from nonkin if ill, but lost ground in
      financial support. The college-educated gained ground in all sorts of support
      from nonkin. DISCUSSION: These results reinforce concern that late middle age is
      a period when men and the less educated become yet more disadvantaged in social
      support, making attention to connectedness yet more critical.

PMID- 24898031
TI  - Psychological Resilience and the Onset of Activity of Daily Living Disability
      Among Older Adults in China: A Nationwide Longitudinal Analysis.
AB  - OBJECTIVES: This study explores the influence of psychological resilience on the
      onset of activities of daily living (ADL) disability among Chinese older adults
      and examines whether this association varies by age. METHOD: Using a sample of
      11,112 older adults from 2 waves of the Chinese Longitudinal Healthy Longevity
      Survey, collected in 2002 and 2005, this study examines whether higher levels of
      psychological resilience (measured by a 5-item scale) predict lower risk of ADL
      incidence during a 3-year follow-up and whether this effect varies by age.
      RESULTS: Higher levels of resilience at the baseline are significantly associated
      with reduced risk of becoming ADL disabled during the 3-year follow-up period,
      independent of baseline sociodemographic characteristics, family support, and
      health. Moreover, resilience by age interaction is detected. Higher levels of
      resilience are more protective against the onset of disability for the younger
      old (aged 65-84) than the oldest old (aged 85 and older). DISCUSSION: Among older
      adults in China, psychological resilience is a protective factor against ADL
      disability, and the benefits are particularly significant for older adults
      younger than 85 years.

PMID- 24898032
TI  - Spatial distribution and environmental factors associated to phlebotomine fauna
      in a border area of transmission of visceral leishmaniasis in Mato Grosso do Sul,
      Brazil.
AB  - BACKGROUND: Mato Grosso do Sul has been undergoing a process of urbanization
      which results in loss of native vegetation. This withdrawal makes vectors of man
      and domestic animals closer, causing changes in the epidemiology of diseases such
      as American Visceral Leishmaniasis. The aim of the study was to evaluate the
      phlebotomine fauna and environmental issues related to the transmission of AVL in
      Ponta Pora, Mato Grosso do Sul, between 2009 and 2010. METHODS: Vegetation of the
      urban area was evaluated by Normalized Difference Vegetation Index (NDVI),
      Normalized Difference Water Index (NDWI) and Soil Adjusted Vegetation Index
      (SAVI). RESULTS: The results showed that the phlebotomine fauna of the city
      consists of five species, especially Lutzomyia longipalpis (Lutz and Neiva,
      1912), the vector of Leishmania (Leishmania) infantum. Predominance of males was
      observed. The insects were captured in greater quantity in the intradomicile. Lu.
      longipalpis was the most frequent and abundant species, present throughout the
      year, with a peak population after the rainy season. Vectors can be found in high
      amounts in forest and disturbed environments. CONCLUSIONS: The finding of Lu.
      longipalpis in regions with little vegetation and humidity suggests that the
      species is adapted to different sorts of environmental conditions, demonstrating
      its close association with man and the environment it inhabits. The tourist
      feature of Ponta Pora reinforces its epidemiological importance as a vulnerable
      city. The geographical location, bordering Paraguay through dry border, makes
      possible the existence of a corridor of vectors and infected dogs between the two
      countries.

PMID- 24898034
TI  - Synthesis, crystal structure, and magnetic properties of novel intermetallic
      compounds R2Co2SiC (R = Pr, Nd).
AB  - The intermetallic compounds R2Co2SiC (R = Pr, Nd) were prepared from the reaction
      of silicon and carbon in either Pr/Co or Nd/Co eutectic flux. These phases
      crystallize with a new stuffed variant of the W2CoB2 structure type in
      orthorhombic space group Immm with unit cell parameters a = 3.978(4) A, b =
      6.094(5) A, c = 8.903(8) A (Z = 2; R1 = 0.0302) for Nd2Co2SiC. Silicon, cobalt,
      and carbon atoms form two-dimensional flat sheets, which are separated by
      puckered layers of rare-earth cations. Magnetic susceptibility measurements
      indicate that the rare earth cations in both analogues order ferromagnetically at
      low temperature (TC ~ 12 K for Nd2Co2SiC and TC ~ 20 K for Pr2Co2SiC). Single
      crystal neutron diffraction data for Nd2Co2SiC indicate that Nd moments initially
      align ferromagnetically along the c axis around ~12 K, but below 11 K, they tilt
      slightly away from the c axis, in the ac plane. Electronic structure calculations
      confirm the lack of spin polarization for Co 3d moments. 

PMID- 24898033
TI  - B and N isolate-doped graphitic carbon nanosheets from nitrogen-containing ion
      exchanged resins for enhanced oxygen reduction.
AB  - B,N-codoped carbon nanostructures (BNCS) can serve as alternative low-cost metal
      free electrocatalysts for oxygen reduction reactions (ORR). However, the
      compensation effect between the p- (B atoms) and n-type (N atoms) dopants would
      make the covalent boron-nitride (BN) easily formed during the synthesis of BNCS,
      leading to a unsatisfactory ORR activity. Therefore, it has been challenging to
      develop facile and rapid synthetic strategies for highly active BNCS without
      forming the direct covalent BN. Here, a facile method is developed to prepare B
      and N isolate-doped graphitic nanosheets (BNGS) by using iron species for saving
      N element and simultaneous doping the B element from nitrogen-containing ion
      exchanged resins (NR). The resulting BNGS exhibits much more onset potential
      (Eonset) compared with the B-doped graphitic carbon nanosheets (BGS), N-doped
      graphitic carbon nanosheets (NGS), as well as B,N-codoped disorder carbon (BNC).
      Moreover, the BNGS shows well methanol tolerance propery and excellent stability
      (a minimal loss of activity after 5,000 potential cycles) compared to that of
      commercial Pt/C catalyst. The goog performance for BNGS towards ORR is attributed
      to the synergistic effect between B and N, and the well electrons transport
      property of graphitic carbon in BNGS. 

PMID- 24898035
TI  - Acrylate-induced nail contact allergy.

PMID- 24898036
TI  - Continuity of care during end of life: an evolutionary concept analysis.
AB  - PURPOSE: The purpose of this study was to clarify the concept of continuity of
      care during the end of life with a focus on the patient's perspective. METHODS:
      Rodgers' method of evolutionary concept analysis was used. The analysis was based
      on literature published in English in the databases Cumulative Index for Nursing
      and Allied Health Literature, Medline, and PsycINFO. FINDINGS: Analysis revealed
      that the continuity at life's end is a dynamic process that depends on the
      interaction among patients, families, and providers, and is strictly interwoven
      with the patient's time perception. CONCLUSION: This analysis showed the
      complexities surrounding the patient's experience of continuity at life's end.
      IMPLICATION FOR NURSING: Nurses can benefit from a deeper understanding of the
      patient's experience, both theoretically and in practice.

PMID- 24898037
TI  - Phenotypic outcomes of imprinted gene models in mice: elucidation of pre- and
      postnatal functions of imprinted genes.
AB  - Genomic imprinting is an epigenetic process causing expression of a subset of
      genes in a parent-of-origin-specific manner. Among vertebrates, only therian
      mammals have been demonstrated to imprint, indicating that placentation and
      imprinting arose at similar time points in evolution and that imprinting may be
      involved in key mammal-specific processes. However, although several theories
      have been posited to explain the evolution of imprinting, each has shortcomings
      and none fully explains the wide variety of genes regulated by imprinting. In
      this review, we catalog the phenotypes associated with genetic mutation and
      overexpression at particular imprinted loci in order to consider the wide impact
      of imprinted genes on development. In addition to the well-described roles of
      imprinted genes in prenatal growth and placentation, more recent data emphasize
      that imprinted genes are critical for specific aspects of postnatal mammalian
      development involving adaptive processes, metabolism, and behavior. 

PMID- 24898038
TI  - The evolutionary origin of the vertebrate body plan: the problem of head
      segmentation.
AB  - The basic body plan of vertebrates, as typified by the complex head structure,
      evolved from the last common ancestor approximately 530 Mya. In this review, we
      present a brief overview of historical discussions to disentangle the various
      concepts and arguments regarding the evolutionary development of the vertebrate
      body plan. We then explain the historical transition of the arguments about the
      vertebrate body plan from merely epistemological comparative morphology to
      comparative embryology as a scientific treatment on this topic. Finally, we
      review the current progress of molecular evidence regarding the basic vertebrate
      body plan, focusing on the link between the basic vertebrate body plan and the
      evolutionarily conserved developmental stages (phylotypic stages). 

PMID- 24898039
TI  - The pivotal regulatory landscape of RNA modifications.
AB  - Posttranscriptionally modified nucleosides in RNA play integral roles in the
      cellular control of biological information that is encoded in DNA. The
      modifications of RNA span all three phylogenetic domains (Archaea, Bacteria, and
      Eukarya) and are pervasive across RNA types, including messenger RNA (mRNA),
      transfer RNA (tRNA), ribosomal RNA (rRNA), and (less frequently) small nuclear
      RNA (snRNA) and microRNA (miRNA). Nucleotide modifications are also one of the
      most evolutionarily conserved properties of RNAs, and the sites of modification
      are under strong selective pressure. However, many of these modifications, as
      well as their prevalence and impact, have only recently been discovered. Here, we
      examine both labile and permanent modifications, from simple methylation to
      complex transcript alteration (RNA editing and intron retention); detail the
      models for their processing; and highlight remaining questions in the field of
      the epitranscriptome. 

PMID- 24898040
TI  - Personalized pharmacogenomics: predicting efficacy and adverse drug reactions.
AB  - Drug response varies between individuals owing to disease heterogeneity,
      environmental factors, and genetic factors. Genetic factors can affect both the
      pharmacokinetics and pharmacodynamics of a drug, leading to changes in local and
      systemic drug exposure and/or changes in the function of the drug target,
      altering drug response. Several pharmacogenetic biomarkers are already utilized
      in clinical practice and have been shown to improve clinical outcomes. However, a
      large number of other biomarkers have never made it beyond the discovery stage.
      Concerted effort is needed to improve the translation of pharmacogenetic
      biomarkers into clinical practice, and this will involve the use of standardized
      phenotyping and genotyping strategies, collaborative work, multidisciplinary
      approaches to identifying and replicating associations, and cooperation with
      industry to facilitate translation and commercialization. Acceptance of these
      approaches by clinicians, regulators, patients, and the public will be important
      in determining future success. 

PMID- 24898041
TI  - The genetics of skin fragility.
AB  - Genetic skin fragility manifests with diminished resistance of the skin and
      mucous membranes to external mechanical forces and with skin blistering,
      erosions, and painful wounds as clinical features. Skin fragility disorders,
      collectively called epidermolysis bullosa, are caused by mutations in 18 distinct
      genes that encode proteins involved in epidermal integrity and dermal-epidermal
      adhesion. The genetic spectrum, along with environmental and genetic modifiers,
      creates a large number of clinical phenotypes, spanning from minor localized
      lesions to severe generalized blistering, secondary skin cancer, or early demise
      resulting from extensive loss of the epidermis. Laboratory investigations of skin
      fragility have greatly augmented our understanding of genotype-phenotype
      correlations in epidermolysis bullosa and have also advanced skin biology in
      general. Current translational research concentrates on the development of
      biologically valid treatments with therapeutic genes, cells, proteins, or small
      molecule compounds in preclinical settings or human pilot trials. 

PMID- 24898042
TI  - The evolutionary genomics of cichlid fishes: explosive speciation and adaptation
      in the postgenomic era.
AB  - With more than 1,500 species, cichlid fishes provide textbook examples of recent
      and diverse adaptive radiations, rapid rates of speciation, and the parallel
      evolution of adaptive phenotypes among both recently and distantly related
      lineages. This extraordinary diversity has attracted considerable interest from
      researchers across several biological disciplines. Their broad phenotypic
      variation coupled with recent divergence makes cichlids an ideal model system for
      understanding speciation, adaptation, and phenotypic diversification. Genetic
      mapping, genome-wide analyses, and genome projects have flourished in the past
      decade and have added new insights on the question of why there are so many
      cichlids. These recent findings also show that the sharing of older DNA
      polymorphisms is extensive and suggest that linage sorting is incomplete and that
      adaptive introgression played a role in the African radiation. Here, we review
      the results of genetic and genomic research on cichlids in the past decade and
      suggest some potential avenues to further exploit the potential of the cichlid
      model system to provide a better understanding of the genomics of adaptation and
      speciation. 

PMID- 24898043
TI  - The impact of chronic conditions of care recipients on the labour force
      participation of informal carers in Australia: which conditions are associated
      with higher rates of non-participation in the labour force?
AB  - BACKGROUND: Little is known about the effects of personal and other
      characteristics of care recipients on the behaviour of carers. The aim of this
      study is to examine the association between the main chronic (disabling)
      condition of care recipients and the likelihood of their (matched) primary carers
      aged 15-64 years being out of the labour force. METHODS: We conducted a
      retrospective analysis of cross-sectional data from the Australian Bureau of
      Statistics 2009 Survey of Disability, Ageing and Carers (SDAC) for people aged 15
      64 years. We estimated the rates of exit from the labour force for primary carers
      and non-carers; rates of chronic disease occurrence for care recipients living
      with their main carers; odds ratios of primary carers being out of the labour
      force associated with the main chronic condition of their care recipient who
      lives with them. RESULTS: From the 2009 SDAC, we identified 1,268 out of 37,186
      eligible participants who were primary carers of a care recipient who lived with
      them. Of these, 628 (49.5%) were out of the labour force. Most common diseases of
      care recipients were: back problems (12%); arthritis and related disorders (10%);
      diseases of the nervous system (such as multiple sclerosis, epilepsy, cerebral
      palsy) (7.4%); and conditions originating in the perinatal period or congenital
      malformations, deformations and chromosomal abnormalities (5.1%). When adjusted
      for age, sex, education and whether have a long term chronic condition of
      informal carers, the five conditions of care recipients associated with the
      highest odds of their carers being out of the labour force were: head
      injury/acquired brain damage; neoplasms, blood diseases, disorders of the immune
      system; leg/knee/foot/hip damage from injury/accident; dementia, Parkinson's
      disease, Alzheimer's disease; and diseases of the musculoskeletal system and
      connective tissue (osteoporosis). CONCLUSIONS: This study identifies the type of
      conditions that have the greatest impact on the labour force participation of
      informal carers - previously unavailable information for Australia. Australia,
      like most developed countries, is facing several skills shortages and an ageing
      population. These governments will need to adopt novel and more wholistic
      approaches to increase the labour force participation of diverse groups. Informal
      carers are one such group.

PMID- 24898044
TI  - Predictors of voluntary HIV counselling and testing services utilization among
      people with disabilities in Addis Ababa, Ethiopia.
AB  - The study investigated HIV testing prevalence and factors associated with the
      utilization of voluntary HIV counselling and testing (VCT) services among
      individuals with disabilities in Addis Ababa. The analysis was based on a survey
      of 209 men and 203 women with disabilities, aged 15-49, who had ever heard about
      HIV and AIDS in four sub-cities in Addis Ababa. HIV testing prevalence was 53.2%,
      with no significant difference between males and females. Comprehensive HIV
      knowledge, living with spouse, and religious affiliations positively predicted
      utilization of VCT services among participants. Living with both parents and
      having physical or mental/intellectual disabilities were negative predictors of
      VCT services utilization. More research on the predictors of utilization of VCT
      services by gender and urban/rural divides are needed among people with
      disabilities. 

PMID- 24898045
TI  - IL36RN mutation causing generalized pustular psoriasis in a Palestinian patient.
AB  - Deficiency of interleukin-36 (IL-36) receptor antagonist (DITRA; OMIM 614204) is
      a rare autoinflammatory disorder characterized by periodic fever associated with
      a generalized erythematous and pustular skin rash. A 6-year-old Arab-Palestinian
      boy presented with a history of periodic fever and unremitting, erythematous,
      scaly skin rash accompanied by widespread pustules that had been present since
      the age of one month. The patient's skin lesions were compatible with generalized
      pustular psoriasis. Sequence analysis revealed a homozygous nonsense mutation,
      c.28C>T (p.Arg10X) in the IL36RN gene. The patient improved with oral
      methotrexate in combination with oral and topical corticosteroids. The molecular
      basis for DITRA has only recently been identified, and the mutation spectrum for
      this disorder in many populations is still obscure. This paper reports the
      presence of the c.28C>T mutation in an Arab-Palestinian patient and thus
      represents the first description of this mutation in a non-Japanese subject. 

PMID- 24898046
TI  - Comparison of characteristics of international and national databases for
      rheumatoid arthritis: a systematic literature review.
AB  - OBJECTIVES: To evaluate current (inter)national registers and observational
      cohorts in Europe, and to compare inclusion criteria, aims, collected data, and
      participation in the European League Against Rheumatism (EULAR) repository.
      METHOD: We performed a systematic search strategy in six literature databases for
      rheumatoid arthritis (RA). Publications reporting European (inter)national
      prospective registers/cohorts including > 200 RA patients with at least half a
      year of follow-up were selected. RESULTS: In total, 417 articles and abstracts
      were included from four international databases and 39 national
      databases/cohorts. International databases were of similar design, frequency of
      data collection and selection criteria and are mostly initiated to monitor and
      compare clinical patient care among countries. National databases/cohorts vary in
      aims and inclusion criteria. Half of the national registers are connected to the
      EULAR repository of databases. CONCLUSIONS: Our findings indicate that, among
      researchers, there is little awareness of guidelines to set up registers or
      cohorts and of the existence of the database collaboration network of EULAR.

PMID- 24898047
TI  - The Endurant stent graft for endovascular aneurysm repair.
AB  - Endovascular aneurysm repair (EVAR) has become an established therapy for many
      patients with abdominal aortic aneurysms. This minimally invasive procedure has
      lower operative mortality and similar long-term survival rates compared to open
      surgical treatment. However, several patients are still unsuitable for EVAR
      because of their aneurysm neck or iliac artery anatomy, and secondly, re
      intervention rates are higher after EVAR than after open aneurysm exclusion.
      Current challenges in the development of new stent grafts are to make more
      patients eligible for EVAR, including patients with challenging anatomy, and to
      decrease re-intervention rates. A range of different stent grafts now exist, and
      in the search for a device with the widest applicability and the least
      complications, the Endurant stent graft is a recent addition. This device offers
      wider inclusion criteria. Despite this, first results show comparable
      complication rates compared to other stent grafts, and long-term follow-up
      studies are underway. 

PMID- 24898048
TI  - A biotin-guided fluorescent-peptide drug delivery system for cancer treatment.
AB  - Herein, we present a fluorescent-peptide drug delivery system composed of biotin
      naphthalimide-HJ inhibitor peptide2, prodrug 1. Treatment of 1 to biotin receptor
      positive HepG2 cells, which are resistant to high concentrations of the HJ
      inhibitor peptide2, decreased cell viability and increased intracellular
      fluorescence. 

PMID- 24898049
TI  - Colonic perforation in a neonate with an anorectal malformation.

PMID- 24898051
TI  - The Sixth International Meeting on Synthetic Biology (SB6.0) special issue
      editorial.

PMID- 24898050
TI  - Dysregulation of collagen production in diabetes following recurrent skin injury:
      contribution to the development of a chronic wound.
AB  - Recurrent injury has been implicated in the development of chronic diabetic
      wounds. We have developed a chronic diabetic wound model based upon recurrent
      injury in diabetic mice. We hypothesized that dysregulation of collagen
      production at both the mRNA and microRNA levels contributes to the development of
      chronic diabetic wounds. To test this, both diabetic and nondiabetic mice were
      made to undergo recurrent injury. Real-time PCR for TGF-beta1, SMAD-3,
      Col1alpha1, Col3alpha1, microRNA-25, and microRNA-29a and Western blot for
      collagen I and III were performed 7 days following each injury. Diabetic wounds
      displayed decreased collagen at all time points. This was associated with
      dysregulated collagen production at both the gene and microRNA levels at all time
      points. Following the final injury, however, diabetic collagen production
      significantly improved. This appeared to be due to a substantial decrease in both
      microRNAs as well as an increase in the expression of collagen pathway genes.
      That dysregulated collagen production progressed throughout the course of
      wounding suggests that this is one factor contributing to the development of
      chronic diabetic wounds. Future studies using this model will allow for the
      determination of other factors that may also contribute to the development and/or
      persistence of chronic diabetic wounds. 

PMID- 24898054
TI  - Rewiring the wax ester production pathway of Acinetobacter baylyi ADP1.
AB  - Wax esters are industrially relevant high-value molecules. For sustainable
      production of wax esters, bacterial cell factories are suggested to replace the
      chemical processes exploiting expensive starting materials. However, it is well
      recognized that new sophisticated solutions employing synthetic biology toolbox
      are required to improve and tune the cellular production platform to meet the
      product requirements. For example, saturated wax esters with alkanol chain
      lengths C12 or C14 that are convenient for industrial uses are rare among
      bacteria. Acinetobacter baylyi ADP1, a natural producer of wax esters, is a
      convenient model organism for studying the potentiality and modifiability of wax
      esters in a natural host by means of synthetic biology. In order to establish a
      controllable production platform exploiting well-characterized biocomponents, and
      to modify the wax ester synthesis pathway of A. baylyi ADP1 in terms product
      quality, a fatty acid reductase complex LuxCDE with an inducible arabinose
      promoter was employed to replace the natural fatty acyl-CoA reductase acr1 in
      ADP1. The engineered strain was able to produce wax esters by the introduced
      synthetic pathway. Moreover, the fatty alkanol chain length profile of wax esters
      was found to shift toward shorter and more saturated carbon chains, C16:0
      accounting for most of the alkanols. The study demonstrates the potentiality of
      recircuiting a biosynthesis pathway in a natural producer, enabling a regulated
      production of a customized bioproduct. Furthermore, the LuxCDE complex can be
      potentially used as a well-characterized biopart in a variety of synthetic
      biology applications involving the production of long-chain hydrocarbons. 

PMID- 24898055
TI  - "Is there a gun in the home?" Assessing the risks of gun ownership in older
      adults.
AB  - An important ethical and safety concern that geriatricians, primary care
      providers, and home health professionals need to address is gun ownership by
      elderly adults. Those aged 65 and older now have the highest rate of gun
      ownership in America, and they also have a high prevalence of depression and
      suicide. Dementia can add additional layers of risk. Even older gun owners who
      are otherwise intellectually intact may benefit from information about gun safety
      with the increasing numbers of children being cared for by grandparents. Health
      professionals should ask patients, "Is there a gun in the home?" in the clinic
      and during home visits. Healthcare professionals must have knowledge and skills
      to address safe gun ownership in elderly adults. The 5 L's (Locked, Loaded,
      Little children, feeling Low, Learned owner) will assist professionals in
      addressing all aspects of safe ownership. 

PMID- 24898056
TI  - The correlation between endoscopic and histopathological measurements in
      colorectal polyps.
AB  - AIMS: Colorectal adenomas measuring 10 mm or more are at increased neoplastic
      risk and therefore undergo more rigorous follow-up. Currently there is no
      standardized method of assessing polyp size. We aimed to examine the correlation
      between endoscopic and histopathological measurements to determine the most
      appropriate method for clinical use. METHODS AND RESULTS: Colorectal polyps
      removed between November 2008 and January 2009 were identified. Routine
      endoscopic and histopathological measurements were determined retrospectively
      from the reports. Glass slide measurements using a ruler and magnified graticule
      were performed prospectively on all cases. Fifty cases also underwent high
      resolution digital scanning and tissue morphometry. After exclusions, 352 polyps
      from 210 patients were identified, including 235 adenomas, 107 hyperplastic
      polyps and 10 other lesions. Only 89% of adenomas had a documented endoscopic
      measurement and 22% a histopathological measurement. The median endoscopic
      measurement was significantly greater, resulting in 13% of patients being
      misclassified as high or low risk. CONCLUSIONS: There are significant differences
      between endoscopic and histopathological measurement, and currently
      histopathologists frequently fail to accurately measure adenomas.
      Histopathological measurement should still be considered as the gold standard;
      however, there must be a hierarchy of measurements to take account of the
      practical limitations of sample fragmentation.

PMID- 24898057
TI  - Signalling: FOXM1 and CENPF: co-pilots driving prostate cancer.

PMID- 24898059
TI  - Glioblastoma: Cancer stem cell knockout.

PMID- 24898060
TI  - Microenvironment: An exercise in restraint.

PMID- 24898061
TI  - The effectiveness of a 0.05 blood alcohol concentration (BAC) limit for driving
      in the United States.
AB  - The National Transportation Safety Board recently recommended that states
      establish a per se blood alcohol concentration (BAC) limit of 0.05 or lower for
      all drivers who are not already required to adhere to lower BAC limits in a
      national effort to reduce alcohol-impaired driving. There is strong evidence for
      adopting this recommendation. A comprehensive review of the literature on BAC
      limits was conducted. The research indicates that virtually all drivers are
      impaired regarding at least some driving performance measures at a 0.05 BAC. The
      risk of being involved in a crash increases significantly at 0.05 BAC and above.
      The relative risk of being killed in a single-vehicle crash with BACs of 0.05
      0.079 is 7-21 times higher than for drivers at 0.00 BAC. Lowering the BAC limit
      from 0.08 to 0.05 has been a proven effective countermeasure in numerous
      countries around the world. Most Americans do not believe a person should drive
      after having two or three drinks in 2 hours. It takes at least four drinks for
      the average 170-pound male to exceed 0.05 BAC in 2 hours (three drinks for the
      137-pound female). Most industrialized nations have established a 0.05 BAC limit
      or lower for driving. Progress in reducing the proportion of drivers in fatal
      crashes with illegal BACs has stalled over the past 15 years. Lowering the BAC
      limit for driving from the current 0.08 to 0.05 has substantial potential to
      reduce the number of people who drink and drive in the United States and get
      involved in fatal crashes. 

PMID- 24898062
TI  - Coping with low pH: molecular strategies in neutralophilic bacteria.
AB  - As part of their life cycle, neutralophilic bacteria are often exposed to varying
      environmental stresses, among which fluctuations in pH are the most frequent. In
      particular, acid environments can be encountered in many situations from
      fermented food to the gastric compartment of the animal host. Herein, we review
      the current knowledge of the molecular mechanisms adopted by a range of Gram
      positive and Gram-negative bacteria, mostly those affecting human health, for
      coping with acid stress. Because organic and inorganic acids have deleterious
      effects on the activity of the biological macromolecules to the point of
      significantly reducing growth and even threatening their viability, it is not
      unexpected that neutralophilic bacteria have evolved a number of different
      protective mechanisms, which provide them with an advantage in otherwise life
      threatening conditions. The overall logic of these is to protect the cell from
      the deleterious effects of a harmful level of protons. Among the most favoured
      mechanisms are the pumping out of protons, production of ammonia and proton
      consuming decarboxylation reactions, as well as modifications of the lipid
      content in the membrane. Several examples are provided to describe mechanisms
      adopted to sense the external acidic pH. Particular attention is paid to
      Escherichia coli extreme acid resistance mechanisms, the activity of which ensure
      survival and may be directly linked to virulence. 

PMID- 24898058
TI  - New PARP targets for cancer therapy.
AB  - Poly(ADP-ribose) polymerases (PARPs) modify target proteins post-translationally
      with poly(ADP-ribose) (PAR) or mono(ADP-ribose) (MAR) using NAD(+) as substrate.
      The best-studied PARPs generate PAR modifications and include PARP1 and the
      tankyrase PARP5A, both of which are targets for cancer therapy with inhibitors in
      either clinical trials or preclinical development. There are 15 additional PARPs,
      most of which modify proteins with MAR, and their biology is less well
      understood. Recent data identify potentially cancer-relevant functions for these
      PARPs, which indicates that we need to understand more about these PARPs to
      effectively target them.

PMID- 24898063
TI  - Self-assembled nanoparticles as multifunctional drugs for anti-microbial
      therapies.
AB  - A self-assembled nanoparticle containing a photosensitizer and a Trojan-horse
      moiety (cholesterol), binds an anti-TB pro-drug and increases 1000-fold its
      activity against mycobacteria. These minimalist constructs will allow development
      of economically viable, efficient drug preparations for the treatment of drug
      resistant TB infections. 

PMID- 24898064
TI  - Stay-green alleles individually enhance grain yield in sorghum under drought by
      modifying canopy development and water uptake patterns.
AB  - Stay-green is an integrated drought adaptation trait characterized by a distinct
      green leaf phenotype during grain filling under terminal drought. We used sorghum
      (Sorghum bicolor), a repository of drought adaptation mechanisms, to elucidate
      the physiological and genetic mechanisms underpinning stay-green. Near-isogenic
      sorghum lines (cv RTx7000) were characterized in a series of field and managed
      environment trials (seven experiments and 14 environments) to determine the
      influence of four individual stay-green (Stg1-4) quantitative trait loci (QTLs)
      on canopy development, water use and grain yield under post-anthesis drought. The
      Stg QTL decreased tillering and the size of upper leaves, which reduced canopy
      size at anthesis. This reduction in transpirational leaf area conserved soil
      water before anthesis for use during grain filling. Increased water uptake during
      grain filling of Stg near-isogenic lines (NILs) relative to RTx7000 resulted in
      higher post-anthesis biomass production, grain number and yield. Importantly,
      there was no consistent yield penalty associated with the Stg QTL in the
      irrigated control. These results establish a link between the role of the Stg QTL
      in modifying canopy development and the subsequent impact on crop water use
      patterns and grain yield under terminal drought. 

PMID- 24898065
TI  - Estradiol modulation of monoamine metabolism: one possible mechanism underlying
      sex differences in risk for depression and dementia.

PMID- 24898066
TI  - Phyllobilins--the abundant bilin-type tetrapyrrolic catabolites of the green
      plant pigment chlorophyll.
AB  - The seasonal disappearance of the green plant pigment chlorophyll in the leaves
      of deciduous trees has long been a fascinating biological puzzle. In the course
      of the last two and a half decades, important aspects of the previously enigmatic
      breakdown of chlorophyll in higher plants were elucidated. Crucial advances in
      this field were achieved by the discovery and structure elucidation of
      tetrapyrrolic chlorophyll catabolites, as well as by complementary biochemical
      and plant biological studies. Phyllobilins, tetrapyrrolic, bilin-type chlorophyll
      degradation products, are abundant chlorophyll catabolites, which occur in fall
      leaves and in ripe fruit. This tutorial review outlines 'how' chlorophyll is
      degraded in higher plants, and gives suggestions as to 'why' the plants dispose
      of their valuable green pigments during senescence and ripening. Insights into
      chlorophyll breakdown help satisfy basic human curiosity and enlighten school
      teaching. They contribute to fundamental questions in plant biology and may have
      practical consequences in agriculture and horticulture. 

PMID- 24898067
TI  - Trastuzumab emtansine is active on HER-2 overexpressing NSCLC cell lines and
      overcomes gefitinib resistance.
AB  - BACKGROUND: HER-2 represents a relatively new therapeutic target for non small
      cell lung cancer (NSCLC) patients. The incidence for reported HER-2
      overexpression/amplification/mutations ranges from 2 to 20% in NSCLC. Moreover,
      HER-2 amplification is a potential mechanism of resistance to tyrosine kinase
      inhibitors of the epidermal growth factor receptor (EGFR-TKI) (about 10% of
      cases). T-DM1, trastuzumab emtansine is an antibody-drug conjugate composed by
      the monoclonal antibody trastuzumab and the microtubule polymerization inhibitor
      DM1. The activity of T-DM1 has been studied in breast cancer but the role of T
      DM1 in lung cancer remains unexplored. METHODS: Antiproliferative and
      proapoptotic effects of T-DM1 have been investigated in different NSCLC cell
      lines by MTT, crystal violet staining, morphological study and Western blotting.
      HER-2 expression and cell cycle were evaluated by flow cytometry and Western
      blotting. Antibody dependent cell cytotoxicity (ADCC) was measured with a CytoTox
      assay. Xenografted mice model has been generated using a NSCLC cell line to
      evaluate the effect of T-DM1 on tumor growth. Moreover, a morphometric and
      immunohistochemical analysis of tumor xenografts was conducted. RESULTS: In this
      study we investigated the effect of T-DM1 in a panel of NSCLC cell lines with
      different HER-2 expression levels, in H1781 cell line carrying HER-2 mutation and
      in gefitinib resistant HER-2 overexpressing PC9/HER2cl1 cell clone. T-DM1
      efficiently inhibited proliferation with arrest in G2-M phase and induced cell
      death by apoptosis in cells with a significant level of surface expression of HER
      2. Antibody-dependent cytotoxicity assay documented that T-DM1 maintained the
      same activity of trastuzumab. Our data also suggest that targeting HER-2 with T
      DM1 potentially overcomes gefitinib resistance. In addition a correlation between
      cell density/tumor size with both HER-2 expression and T-DM1 activity was
      established in vitro and in an in vivo xenograft model. CONCLUSIONS: Our results
      indicate that targeting HER-2 with T-DM1 may offer a new therapeutic approach in
      HER-2 over-expressing lung cancers including those resistant to EGFR TKIs.

PMID- 24898070
TI  - Acute mastoiditis in children with cochlear implants: is explantation required?
AB  - OBJECTIVE: Acute mastoiditis is an uncommon but challenging condition when it
      occurs in children with cochlear implant. The literature is scarce as to the
      management of this condition with regards to explantation. The objective of the
      study is to determine the need for explantation in patients with cochlear
      implants who suffer from acute mastoiditis. DATA SOURCES: Online medical
      databases-PubMed, Ovid Medline, Ovid Medline in process, Embase, Cochrane
      Library, CINAHL, Biosis, Google Scholar, and Scopus. REVIEW METHODS: A systematic
      review of all publications addressing the treatment of mastoiditis in cochlear
      implant children prior to November 2013 was conducted. Data were collected from
      online medical databases-PubMed, Ovid Medline, Ovid Medline in process, Embase,
      Cochrane Library, CINAHL, Biosis, Google Scholar, and Scopus. The review was
      performed in 3 phases; an initial screening review of abstracts was performed,
      followed by a detailed review of full articles based on inclusion and exclusion
      criteria, and lastly a final review to extract data from selected articles.
      RESULTS: Twelve articles were found eligible for this systematic review including
      a total of 43 patients. Subperiosteal abscess was present in 14.3%. All patients
      received intravenous antibiotics as an initial treatment, and if needed, surgical
      intervention was performed. Only 1 patient required explantation (2.3%).
      CONCLUSION: Prompt, aggressive medical and if needed surgical therapy can help in
      saving the implant and result in a favorable outcome.

PMID- 24898068
TI  - Isocitrate dehydrogenase mutation is frequently observed in giant cell tumor of
      bone.
AB  - Giant cell tumors of bone (GCTB) are benign and locally destructive tumors that
      include osteoclast-type multinuclear giant cells. No available treatment is
      definitively effective in curing GCTB, especially in surgically unresectable
      cases. Isocitrate dehydrogenase (IDH) mutations have been reported not only in
      gliomas and acute myeloid leukemias, but also in cartilaginous tumors and
      osteosarcomas. However, IDH mutations in GCTB have not been investigated. The IDH
      mutations are remarkably specific to arginine 132 (R132) in IDH1 and arginine 172
      (R172) or arginine 140 (R140) in IDH2; IDH1/2 mutations are known to convert
      alpha-ketoglutarate to oncometabolite R(-)-2-hydroxyglutarate. We recently
      reported that the most frequent IDH mutation in osteosarcomas is IDH2-R172S,
      which was detected by MsMab-1, a multispecific anti-IDH1/2 mAb. Herein, we newly
      report the IDH mutations in GCTB, which were stained by MsMab-1 in
      immunohistochemistry. DNA direct sequencing and subcloning identified IDH
      mutations of GCTB as IDH2-R172S (16 of 20; 80%). This is the first report to
      describe IDH mutations in GCTB, and MsMab-1 can be anticipated for use in
      immunohistochemical determination of IDH1/2 mutation-bearing GCTB. 

PMID- 24898071
TI  - Effect of strong fragrance on olfactory detection threshold.
AB  - OBJECTIVE: To assess the olfactory threshold of healthy volunteers at the
      University College Hospital, Ibadan and to investigate the effect of perfume on
      their olfactory detection thresholds. STUDY DESIGN: A quasi-experimental study on
      olfactory detection thresholds of healthy volunteers from September 2013 to
      November 2013. SETTING: Tertiary health institution. SUBJECTS AND METHODS: A
      structured questionniare was administered to the participants in order to obtain
      information on sociodemographics, occupation, ability to perceive smell, use of
      perfume, effects of perfume on appetite and self-confidence, history of allergy,
      and previous nasal surgery. Participants subjectively rated their olfactory
      performance. Subsequently, they had olfactory detection threshold testing done at
      baseline and after exposure to perfume with varied concentrations of n-butanol in
      a forced triple response and staircase fashion. RESULTS: Healthy volunteers, 37
      males and 63 females, were evaluated. Their ages ranged from 19 to 59 years with
      a mean of 31 years +/- 8. Subjectively, 94% of the participants had excellent
      olfactory function. In the pre-exposure forced triple response, 88% were able to
      detect the odor at <=.25 mmol/l concentration while in the post-exposure forced
      triple response, only 66% were able to detect the odor at <=.25 mmol/l
      concentration. There is also a statistical significant difference in the
      olfactory detection threshold score between the pre-exposure and post-exposure
      period in the participants (P < .05). CONCLUSION: Use of strong fragrances
      affects the olfactory detection threshold. Therefore patients and clinicians
      should be aware of this and its effects on the outcome of test of olfaction.

PMID- 24898073
TI  - Balloon dilation of the eustachian tube is indeed a "gizmo" until future research
      proves safety and efficacy.
AB  - In the April 2014 issue of this journal, Richard M. Rosenfeld, MD, MPH, wrote an
      editorial in which he recommends distinguishing "fanciful gizmos from truly
      useful technology," provides 5 criteria to evaluate a gizmo, and includes as one
      of the current ones balloons to "open clogged ears." The implication is that
      balloon dilation for suspected eustachian tube dysfunction-middle ear disease is
      an unproven procedure. Coincidentally, on April 1, the National Institutes of
      Health (NIH) awarded an Exploratory/Development grant to the University of
      Pittsburgh to evaluate this new treatment, which affirms that the NIH agrees that
      this procedure is of uncertain efficacy.

PMID- 24898074
TI  - Contemporary changes with the use of facial nerve monitoring in chronic ear
      surgery.
AB  - OBJECTIVE: There is a growing trend for the routine use of the facial nerve
      monitor (FNM) in chronic ear surgery. We aimed to examine current patterns in the
      use of FNMs in chronic ear surgery. STUDY DESIGN: Descriptive design (survey).
      SETTING: Academic health center. METHODS: A 10-question survey was designed to
      identify level of training, scope of practice, specific otologic surgeries where
      monitoring was most used, and the opinion of respondents regarding the use of
      FNMs as standard of care for chronic and/or middle ear surgery. A randomized list
      of 2000 board-certified members of the American Academy of Otolaryngology-Head
      and Neck Surgery was generated. One thousand subjects received a mailed survey
      with a self-addressed return envelope and 1000 subjects received an emailed
      survey through Surveymonkey.com. RESULTS: There were 359 (36%) surveys returned
      by mail and 258 (26%) surveys returned electronically. Forty-three percent of
      respondents were in private practice, and 31% were fellowship trained in
      otology/neurotology. Sixty-five percent used a FNM in their training and 95% had
      regular access to a FNM. Revision mastoid surgery, cholesteatoma, canal wall down
      mastoidectomy, and facial recess approach were the settings where a FNM was most
      used. Forty-nine percent of respondents felt that a FNM should be used as the
      standard of care in chronic ear surgery; this represents an increase from 32% in
      a similar study done approximately 10 years ago. CONCLUSION: There is a growing
      trend for routine facial nerve monitoring in the setting of chronic ear surgery.

PMID- 24898072
TI  - Electronic nicotine delivery systems ("e-cigarettes"): review of safety and
      smoking cessation efficacy.
AB  - BACKGROUND AND OBJECTIVES: Cigarette smoking is common among cancer patients and
      is associated with negative outcomes. Electronic nicotine delivery systems ("e
      cigarettes") are rapidly growing in popularity and use, but there is limited
      information on their safety or effectiveness in helping individuals quit smoking.
      DATA SOURCES: The authors searched PubMed, Web of Science, and additional sources
      for published empirical data on safety and use of electronic cigarettes as an aid
      to quit smoking. REVIEW METHODS: We conducted a structured search of the current
      literature up to and including November 2013. RESULTS: E-cigarettes currently
      vary widely in their contents and are sometimes inconsistent with labeling.
      Compared to tobacco cigarettes, available evidence suggests that e-cigarettes are
      often substantially lower in toxic content, cytotoxicity, associated adverse
      effects, and secondhand toxicity exposure. Data on the use of e-cigarettes for
      quitting smoking are suggestive but ultimately inconclusive. CONCLUSIONS:
      Clinicians are advised to be aware that the use of e-cigarettes, especially among
      cigarette smokers, is growing rapidly. These devices are unregulated, of unknown
      safety, and of uncertain benefit in quitting smoking. IMPLICATIONS FOR PRACTICE:
      In the absence of further data or regulation, oncologists are advised to discuss
      the known and unknown safety and efficacy information on e-cigarettes with
      interested patients and to encourage patients to first try FDA-approved
      pharmacotherapies for smoking cessation.

PMID- 24898075
TI  - Risk factors for cerebrospinal leak after endoscopic skull base reconstruction
      with nasoseptal flap.
AB  - OBJECTIVE: The use of expanded endonasal surgery (EES) in the treatment of skull
      base neoplasms has increased significantly in recent years. Since 2006, the
      nasoseptal flap (NSF) has become the workhorse for the closure of skull base
      defects involving the anterior and central skull base. We hypothesized that
      defect site impacts the rate of cerebrospinal fluid (CSF) leak following EES.
      STUDY DESIGN: Retrospective cohort study. SETTING/SUBJECTS/METHODS: Patients who
      underwent skull base defect repair using a NSF at the University of California at
      San Francisco (UCSF) minimally invasive skull base center were retrospectively
      reviewed. Patient demographics, disease, and defect location and size were
      recorded along with the presence of a postoperative CSF leak. Data were analyzed
      using Fisher's exact test. RESULTS: One hundred and twenty-one patients met
      inclusion criteria. Ten patients had a NSF failure with CSF leakage, 2 in the
      anterior skull base (frontal sinus, ethmoid, cribriform, planum), and 8 in the
      central skull base (sella, clivus) (P = .047). Dural defect size >=2.0 cm(2) in
      the central skull base strongly correlated with the risk of flap failure (P =
      .034). CONCLUSIONS: This study of endoscopic closure of skull base defects using
      a NSF demonstrates there is an association between both surgical site and dural
      defect size with NSF failure. Expanded defects of the sella and clivus have an
      increased risk of failure and may warrant augmented techniques.

PMID- 24898076
TI  - Patient with Gorlin syndrome and metastatic basal cell carcinoma refractory to
      smoothened inhibitors.
AB  - IMPORTANCE: Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have
      been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel
      targeted therapy against the Hedgehog pathway, because of characteristic
      mutations in these patients. A few cases of disease refractory to oral therapy
      with SMO inhibitors have been reported in patients with Gorlin syndrome and
      nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not
      been documented in this high-risk group. OBSERVATIONS: A man with Gorlin syndrome
      and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs.
      After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his
      lung metastases did not. These lung metastases remained refractory to treatment
      despite institution of a second SMO inhibitor. CONCLUSIONS AND RELEVANCE: We
      report a case of Gorlin syndrome in a patient with metastatic BCC refractory to
      SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous
      tumors did not parallel the responses in the distant site. However, serial
      imaging after diagnosis of metastatic disease can be critical to monitor for
      response to therapy.

PMID- 24898078
TI  - Aerobic fitness and skewness of frequency distribution of continuously measured
      heart rate in adults with brain injury.
AB  - BACKGROUND: Determinant factors of aerobic fitness have not been clearly
      demonstrated in individuals with brain injury. AIM: To investigate the
      relationship between aerobic fitness and gender, age, intensity and total
      duration of aerobic physical activity, and skewness of the frequency distribution
      of 6-h continuous heart rate values in a larger sample of adults with brain
      injury. DESIGN: Cross-sectional and correlative study. SETTING: Research
      laboratory setting. POPULATION: Thirteen adult women and 20 adult men with
      cerebral palsy or stroke participated in this study. METHOD: VO2max was estimated
      using the multistage submaximal cycle ergometer test. Heart rate was recorded
      continuously for 6 h on a weekday. Relationships between predicted VO2max and
      gender, age, intensity and total duration of aerobic physical activity, skewness
      of frequency distribution, and average heart rate over 6 h were determined.
      RESULTS: Significant differences were seen in predicted VO2max between genders (P
      < 0.05). Predicted VO2max correlated significantly only with the skewness of the
      frequency distribution of values for continuous heart rate (r = -0.53, P < 0.01).
      CONCLUSION AND CLINICAL REHABILITATION IMPACT: The results suggest that brief and
      frequent physical activity may also improve aerobic fitness in adults with brain
      injury.

PMID- 24898077
TI  - Construction of an expression system for bioactive IL-18 and generation of
      recombinant canine distemper virus expressing IL-18.
AB  - Interleukin 18 (IL-18) plays an important role in the T-helper-cell type 1 immune
      response against intracellular parasites, bacteria and viral infections. It has
      been widely used as an adjuvant for vaccines and as an anticancer agent. However,
      IL-18 protein lacks a typical signal sequence and requires cleavage into its
      mature active form by caspase 1. In this study, we constructed mammalian
      expression vectors carrying cDNA encoding mature canine IL-18 (cIL-18) or mouse
      IL-18 (mIL-18) fused to the human IL-2 (hIL-2) signal sequence. The expressed
      proIL-18 proteins were processed to their mature forms in the cells. The
      supernatants of cells transfected with these plasmids induced high interferon
      gamma production in canine peripheral blood mononuclear cells or mouse
      splenocytes, respectively, indicating the secretion of bioactive IL-18. Using
      reverse genetics, we also generated a recombinant canine distemper virus that
      expresses cIL-18 or mIL-18 fused to the hIL-2 signal sequence. As expected, both
      recombinant viruses produced mature IL-18 in the infected cells, which secreted
      bioactive IL-18. These results indicate that the signal sequence from hIL-2 is
      suitable for the secretion of mature IL-18. These recombinant viruses can also
      potentially be used as immunoadjuvants and agents for anticancer therapies in
      vivo. 

PMID- 24898079
TI  - Use and management of traditional medicinal plants by Maale and Ari ethnic
      communities in southern Ethiopia.
AB  - BACKGROUND: Around 80% of the people of Ethiopia are estimated to be relying on
      medicinal plants for the treatment of different types of human health problems.
      The purpose of this study was to describe and analyse the use and management of
      medicinal plants used for the treatment of human health problems by the Maale and
      Ari communities in southern Ethiopia. METHODS: Quantitative and qualitative
      ethnobotanical field inquiries and analytical methods including individual and
      focus group discussions (18), observations, individual interviews (n = 74),
      preference ranking and paired comparison were used. Data were collected in three
      study sites and from two markets; the latter surveyed every 15 days from February
      2011 to February 2012. RESULTS: A total of 128 medicinal plant species, belonging
      to 111 genera and 49 families, used as herbal medicine by Maale and Ari
      communities were documented. Predominantly harvested plant parts were leaves,
      which are known to have relatively low impact on medicinal plant resources.
      Species with high familiarity indices included Solanum dasyphyllum, Indigofera
      spicata, Ruta chalepensis, Plumbago zeylanica and Meyna tetraphylla. Low Jaccards
      similarity indices (<= 0.33) indicated little correspondence in medicinal plant
      use among sites and between ethnic communities. The dominant ways of medicinal
      plant knowledge acquisition and transfer is vertical: from parents to children
      through oral means. Gender and site significantly influenced the number of human
      medicinal plants known currently in the study sites. Age was only a factor of
      significance in Maale. Marketing of medicinal plants harvested from wild and semi
      wild stands is not common. Expansion of agricultural land and lack of cultivation
      efforts by local communities are mentioned by locals to affect the availability
      of medicinal plant resources. CONCLUSION: S. dasyphyllum, I. spicata, P.
      zeylanica, M. tetraphylla, and Oxalis radicosa need to be considered for
      phytochemical and pharmacological testing to verify their efficacy and determine
      their dosages. Land use planning and development initiatives in the area and
      beyond need to sharply focus on strategies that could alleviate the major threats
      affecting medicinal plant resources in the landscape and encourage their
      cultivation to enhance their availability and complement ex-and in-situ
      conservation.

PMID- 24898081
TI  - All-printable band-edge modulated ZnO nanowire photodetectors with ultra-high
      detectivity.
AB  - High-performance photodetectors are critical for high-speed optical communication
      and environmental sensing, and flexible photodetectors can be used for a wide
      range of portable or wearable applications. Here we demonstrate the all-printable
      fabrication of polycrystalline nanowire-based high-performance photodetectors on
      flexible substrates. Systematic investigations have shown their ultra-high
      photoconductive gain, responsivity and detectivity up to 3.3 * 10(17) Jones.
      Further analysis shows that their high performance originates from the unique
      band-edge modulation along the nanowire axial direction, where the existence of
      Schottky barriers in series leads to highly suppressed dark current of the device
      and also gives rise to fast photoelectric response to low-intensity optical
      signal owing to barrier height modulation. The discovered rationale in this work
      can be utilized as guideline to design high-performance photodetectors with other
      nanomaterial systems. The developed fabrication scheme opens up possibility for
      future flexible and high-performance integrated optoelectronic sensor circuitry. 

PMID- 24898080
TI  - Fisher's geometric model with a moving optimum.
AB  - Fisher's geometric model has been widely used to study the effects of pleiotropy
      and organismic complexity on phenotypic adaptation. Here, we study a version of
      Fisher's model in which a population adapts to a gradually moving optimum. Key
      parameters are the rate of environmental change, the dimensionality of phenotype
      space, and the patterns of mutational and selectional correlations. We focus on
      the distribution of adaptive substitutions, that is, the multivariate
      distribution of the phenotypic effects of fixed beneficial mutations. Our main
      results are based on an "adaptive-walk approximation," which is checked against
      individual-based simulations. We find that (1) the distribution of adaptive
      substitutions is strongly affected by the ecological dynamics and largely depends
      on a single composite parameter gamma, which scales the rate of environmental
      change by the "adaptive potential" of the population; (2) the distribution of
      adaptive substitution reflects the shape of the fitness landscape if the
      environment changes slowly, whereas it mirrors the distribution of new mutations
      if the environment changes fast; (3) in contrast to classical models of
      adaptation assuming a constant optimum, with a moving optimum, more complex
      organisms evolve via larger adaptive steps.

PMID- 24898082
TI  - Differentially expressed proteins in human breast cancer cells sensitive and
      resistant to paclitaxel.
AB  - The resistance of cancer cells to chemotherapeutic drugs represents a major
      problem in cancer treatment. Despite all efforts, mechanisms of resistance have
      not yet been elucidated. To reveal proteins that could be involved in resistance
      to taxanes, we compared protein expression in whole cell lysates of SK-BR-3
      breast cancer cells sensitive to paclitaxel and in lysates of the same line with
      acquired resistance to paclitaxel. The resistant SK-BR-3 cell line was
      established in our lab. Protein separation was achieved using high-resolution 2D
      electrophoresis, computer analysis and mass spectro-metry. With these techniques
      we identified four proteins with different expression in resistant SK-BR-3 cells,
      i.e., serpin B3, serpin B4, heat shock protein 27 (all three upregulated) and
      cytokeratin 18 (downregulated). Observed changes were confirmed using western
      blot analysis. This study suggests new directions worthy of further study in the
      effort to reveal the mechanism of resistance to paclitaxel in breast cancer
      cells.

PMID- 24898084
TI  - Changes in addressing inequalities in access to hospital care in Andhra Pradesh
      and Maharashtra states of India: a difference-in-differences study using repeated
      cross-sectional surveys.
AB  - OBJECTIVES: To compare the effects of the Rajiv Aarogyasri Health Insurance
      Scheme of Andhra Pradesh (AP) with health financing innovations including the
      Rashtriya Swasthya Bima Yojana (RSBY) in Maharashtra (MH) over time on access to
      and out-of-pocket expenditure (OOPE) on hospital inpatient care. STUDY DESIGN: A
      difference-in-differences (DID) study using repeated cross-sectional surveys with
      parallel control. SETTING: National Sample Survey Organisation of India (NSSO)
      urban and rural 'first stratum units', 863 in AP and 1008 in MH. METHODS: We used
      two cross-sectional surveys: as a baseline, the data from the NSSO 2004 survey
      collected before the Aarogyasri and RSBY schemes were launched; and as
      postintervention, a survey using the same methodology conducted in 2012.
      PARTICIPANTS: 8623 households in AP and 10 073 in MH. MAIN OUTCOME MEASURES:
      Average OOPE, large OOPE and large borrowing per household per year for inpatient
      care, hospitalisation rate per 1000 population per year. RESULTS: Average
      expenditure, large expenditures and large borrowings on inpatient care had
      increased in MH and AP, but the increase was smaller in AP across these three
      measures. DIDs for average expenditure and large borrowings were significant and
      in favour of AP for the rural and the poorest households. Hospitalisation rates
      also increased in both states but more so in AP, although the DID was not
      significant and the subgroup analysis presented a mixed picture. CONCLUSIONS:
      Health innovations in AP had a greater beneficial effect on inpatient care
      related expenditures than innovations in MH. The Aarogyasri scheme is likely to
      have contributed to these impacts in AP, at least in part. However, OOPE
      increased in both states over time. Schemes such as the Aarogyasri and RSBY may
      result in some positive outcomes, but additional interventions may be required to
      improve access to care for the most vulnerable sections of the population.

PMID- 24898085
TI  - Parental marital status and childhood overweight and obesity in Norway: a
      nationally representative cross-sectional study.
AB  - OBJECTIVE: Sociodemographic changes in Norway and other western industrialised
      countries, including family structure and an increasing proportion of cohabiting
      and divorced parents, might affect the prevalence of childhood overweight and
      obesity issues. We aimed to examine whether parental marital status was
      associated with general and abdominal obesity among children. We also sought to
      explore whether the associations differed by gender. DESIGN: Cross-sectional.
      SETTING: 127 primary schools across Norway. PARTICIPANT: 3166 third graders (mean
      age 8.3 years) participating in the nationally representative Norwegian Child
      Growth Study in 2010. MEASUREMENTS: Height, weight and waist circumference were
      objectively measured. The main outcome measures were general overweight
      (including obesity; body mass index >=25 kg/m(2)) using International Obesity
      Task Force (IOTF) cut-offs and abdominal obesity (waist-to-height ratio >=0.5) by
      gender and parental marital status. Prevalence ratios, adjusted for possible
      confounders, were calculated by log-binomial regression. RESULTS: General
      overweight (including obesity) was 1.54 (95% CI 1.21 to 1.95) times more
      prevalent among children of divorced parents compared with children of married
      parents, and the corresponding prevalence ratio for abdominal obesity was 1.89
      (95% CI 1.35 to 2.65). Formal tests of the interaction term parental marital
      status by gender were not statistically significant. However, in gender-specific
      analyses the association between parental marital status and adiposity measures
      was only statistically significant in boys (p=0.04 for general overweight
      (including obesity) and p=0.01 for abdominal obesity). The estimates were robust
      against adjustment for maternal education, family country background and current
      area of residence. CONCLUSIONS: General and abdominal obesities were more
      prevalent among children of divorced parents. This study provides valuable
      information by focusing on societal changes in order to identify vulnerable
      groups.

PMID- 24898086
TI  - Can you refuse these discounts? An evaluation of the use and price discount
      impact of price-related promotions among US adult smokers by cigarette
      manufacturers.
AB  - OBJECTIVES: The raising unit price of cigarette has been shown to be one of the
      most effective ways of reducing cigarette consumption and increasing rates of
      successful quitting. However, researchers have shown that price-sensitive smokers
      have used a variety of strategies to mitigate the effect of the rising price of
      cigarettes on their smoking habits. In particular, 23-34% of adult smokers in the
      US use cheaper brands, and 18-55% use coupons or promotions. Little is known
      about the discount use by type of brands. As such, the main purpose of this
      analysis is to evaluate the uses and price discount effects of these price
      related discounts by manufacturers and major brands. SETTING: An analysis based
      on the cross-sectional 2009-2010 National Adult Tobacco Survey (NATS).
      PARTICIPANTS: 11 766 current smokers aged 18 or above in the USA. PRIMARY OUTCOME
      MEASURES: Price-related discount was defined as smokers who used coupons,
      rebates, buy-one-get-one-free, two-for-one or any other special promotions for
      their last cigarettes purchase. RESULTS: The use of price-related discounts and
      associated price impact vary widely by cigarette manufacturer and brand.
      Approximately one of three Camel, one of four Marlboro and one of eight Newport
      smokers used price-related discounts on their latest cigarette purchases. The
      average price reductions of discounts offered by Philip Morris (PM) or R.J.
      Reynolds (RJR) were around 29 cents per pack while that of Lorillard (Newport
      only) was 24 cents per pack. Cigarette brands that provided significant per pack
      price reductions include: PM Marlboro (28 cents), RJR brand Camel (41 cents),
      Doral (50 cents), Kool (73 cents) and Salem (80 cents), and Lorillard Newport (24
      cents). CONCLUSIONS: Policies that decrease price-minimisation strategies will
      benefit public health.

PMID- 24898083
TI  - Histone deacetylase inhibitors and cell death.
AB  - Histone deacetylases (HDACs) are a vast family of enzymes involved in chromatin
      remodeling and have crucial roles in numerous biological processes, largely
      through their repressive influence on transcription. In addition to modifying
      histones, HDACs also target many other non-histone protein substrates to regulate
      gene expression. Recently, HDACs have gained growing attention as HDAC-inhibiting
      compounds are being developed as promising cancer therapeutics. Histone
      deacetylase inhibitors (HDACi) have been shown to induce differentiation, cell
      cycle arrest, apoptosis, autophagy and necrosis in a variety of transformed cell
      lines. In this review, we mainly discuss how HDACi may elicit a therapeutic
      response to human cancers through different cell death pathways, in particular,
      apoptosis and autophagy. 

PMID- 24898088
TI  - Knee moments of anterior cruciate ligament reconstructed and control participants
      during normal and inclined walking.
AB  - OBJECTIVES: Prior injury to the knee, particularly anterior cruciate ligament
      (ACL) injury, is known to predispose one to premature osteoarthritis (OA). The
      study sought to explore if there was a biomechanical rationale for this process
      by investigating changes in external knee moments between people with a history
      of ACL injury and uninjured participants during walking: (1) on different surface
      inclines and (2) at different speeds. In addition we assessed functional
      differences between the groups. PARTICIPANTS: 12 participants who had undergone
      ACL reconstruction (ACLR) and 12 volunteers with no history of knee trauma or
      injury were recruited into this study. Peak knee flexion and adduction moments
      were assessed during flat (normal and slow speed), uphill and downhill walking
      using an inclined walkway with an embedded Kistler Force plate, and a ten-camera
      Vicon motion capture system. Knee injury and Osteoarthritis Outcome Score (KOOS)
      was used to assess function. Multivariate analysis of variance (MANOVA) was used
      to examine statistical differences in gait and KOOS outcomes. RESULTS: No
      significant difference was observed in the peak knee adduction moment between
      ACLR and control participants, however, in further analysis, MANOVA revealed that
      ACLR participants with an additional meniscal tear or collateral ligament damage
      (7 participants) had a significantly higher adduction moment (0.33+/-0.12 Nm/kg
      m) when compared with those with isolated ACLR (5 participants, 0.1+/-0.057 Nm/kg
      m) during gait at their normal speed (p<0.05). A similar (non-significant) trend
      was seen during slow, uphill and downhill gait. CONCLUSIONS: Participants with an
      isolated ACLR had a reduced adductor moment rather an increased moment, thus
      questioning prior theories on OA development. In contrast, those participants who
      had sustained associated trauma to other key knee structures were observed to
      have an increased adduction moment. Additional injury concurrent with an ACL
      rupture may lead to a higher predisposition to osteoarthritis than isolated ACL
      deficiency alone.

PMID- 24898087
TI  - Failure to address potential bias in non-randomised controlled clinical trials
      may cause lack of evidence on patient-reported outcomes: a method study.
AB  - OBJECTIVES: We conducted a workup of a previously published systematic review and
      aimed to analyse why most of the identified non-randomised controlled clinical
      trials with patient-reported outcomes did not match a set of basic quality
      criteria. SETTING: There were no limits on the level of care and the geographical
      location. PARTICIPANTS: The review evaluated permanent interstitial low-dose rate
      brachytherapy in patients with localised prostate cancer and compared that
      intervention with alternative procedures such as external beam radiotherapy,
      radical prostatectomy and no primary therapy. PRIMARY OUTCOME MEASURE: Fulfilment
      of basic inclusion criteria according to a Participants, Interventions,
      Comparisons, Outcomes (PICO) framework and accomplishment of requirements to
      contain superimposed risk of bias. RESULTS: We found that 21 of 50 excluded non
      randomised controlled trials did not meet the PICO inclusion criteria. The
      remaining 29 studies showed a lack in the quality of reporting. The resulting
      flaws included attrition bias due to loss of follow-up, lack of reporting
      baseline data, potential confounding due to unadjusted data and lack of
      statistical comparison between groups. CONCLUSIONS: With respect to the reporting
      of patient-reported outcomes, active efforts are required to improve the quality
      of reporting in non-randomised controlled trials concerning permanent
      interstitial low-dose rate brachytherapy in patients with localised prostate
      cancer.

PMID- 24898089
TI  - START (STrAtegies for RelaTives) coping strategy for family carers of adults with
      dementia: qualitative study of participants' views about the intervention.
AB  - OBJECTIVES: To analyse the experience of individual family carers of people with
      dementia who received a manual-based coping strategy programme (STrAtegies for
      RelaTives, START), demonstrated in a randomised-controlled trial to reduce
      affective symptoms. DESIGN: A qualitative study using self-completed
      questionnaires exploring the experience of the START intervention. Two
      researchers transcribed, coded and analysed completed questionnaires
      thematically. SETTING: Three mental health and one neurology dementia clinic in
      South East England. PARTICIPANTS: Participants were primary family carers of a
      patient diagnosed with dementia who provided support at least weekly to their
      relative. We invited those in the treatment group remaining in the START study at
      2 years postrandomisation (n=132) to participate. 75 people, comprising a maximum
      variation sample, responded. PRIMARY AND SECONDARY OUTCOME MEASURES: (1)
      Important aspects of the therapy. (2) Continued use of the intervention after the
      end of the therapy. (3) Unhelpful aspects of the therapy and suggestions for
      improvement. (4) Appropriate time for intervention delivery. RESULTS: Carers
      identified several different components as important: relaxation techniques,
      education about dementia, strategies to help manage the behaviour of the person
      with dementia, contact with the therapist and changing unhelpful thoughts. Two
      thirds of the participants reported that they continue to use the intervention's
      techniques at 2-year follow up. Few participants suggested changes to the
      intervention content, but some wanted more sessions and others wanted the
      involvement of more family members. Most were happy with receiving the
      intervention shortly after diagnosis, although some relatives of people with
      moderate dementia thought it should have been delivered at an earlier stage.
      CONCLUSIONS: Participants' varied responses about which aspects of START were
      helpful suggest that a multicomponent intervention is suited to the differing
      circumstances of dementia carers, providing a range of potentially helpful
      strategies. The continued use of the strategies 2 years after receiving the
      intervention could be a mechanism for the intervention remaining effective.

PMID- 24898090
TI  - Environments, risk and health harms: a qualitative investigation into the illicit
      use of anabolic steroids among people using harm reduction services in the UK.
AB  - OBJECTIVES: The illicit use of anabolic steroids among the gym population
      continues to rise, along with the number of steroid using clients attending harm
      reduction services in the UK. This presents serious challenges to public health.
      Study objectives were to account for the experiences of anabolic steroid users
      and investigate how 'risk environments' produce harm. METHODS: Qualitative face
      to-face interviews with 24 users of anabolic steroids engaged with harm reduction
      services in the UK. RESULTS: Body satisfaction was an important factor when
      deciding to start the use of anabolic steroids. Many users were unaware of the
      potential dangers of using drugs from the illicit market, whereas some had
      adopted a range of strategies to negotiate the hazards relating to the use of
      adulterated products, including self-experimentation to gauge the perceived
      efficacy and unwanted effects of these drugs. Viewpoints, first-hand anecdotes,
      norms and practices among groups of steroid users created boundaries of
      'sensible' drug use, but also promoted practices that may increase the chance of
      harms occurring. Established users encouraged young users to go to harm reduction
      services but, at the same time, promoted risky injecting practices in the belief
      that this would enhance the efficacy of anabolic steroids. CONCLUSIONS: Current
      steroid-related viewpoints and practices contribute to the risk environment
      surrounding the use of these drugs and may undermine the goal of current public
      health strategies including harm reduction interventions. The level of harms
      among anabolic steroid users are determined by multiple and intertwining factors,
      in addition to the harms caused by the pharmacological action or injury and
      illness associated with incorrect injecting techniques.

PMID- 24898091
TI  - Rationale and study design of the Adaptive study of IL-2 dose on regulatory T
      cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose
      finding trial.
AB  - INTRODUCTION: CD4 T regulatory cells (Tregs) are crucial for the maintenance of
      self-tolerance and are deficient in many common autoimmune diseases such as type
      1 diabetes (T1D). Interleukin 2 (IL-2) plays a major role in the activation and
      function of Tregs and treatment with ultra-low dose (ULD) IL-2 could increase
      Treg function to potentially halt disease progression in T1D. However, prior to
      embarking on large phase II/III clinical trials it is critical to develop new
      strategies for determining the mechanism of action of ULD IL-2 in participants
      with T1D. In this mechanistic study we will combine a novel trial design with a
      clinical grade Treg assay to identify the best doses of ULD IL-2 to induce
      targeted increases in Tregs. METHOD AND ANALYSIS: Adaptive study of IL-2 dose on
      regulatory T cells in type 1 diabetes (DILT1D) is a single centre non-randomised,
      single dose, open label, adaptive dose-finding trial. The primary objective of
      DILT1D is to identify the best doses of IL-2 to achieve a minimal or maximal Treg
      increase in participants with T1D (N=40). The design has an initial learning
      phase where pairs of participants are assigned to five preassigned doses followed
      by an interim analysis to determine the two Treg targets for the reminder of the
      trial. This will then be followed by an adaptive phase which is fully sequential
      with an interim analysis after each participant is observed to determine the
      choice of dose based on the optimality criterion to minimise the determinant of
      covariance of the estimated target doses. A dose determining committee will
      review all data available at the interim(s) and then provide decisions regarding
      the choice of dose to administer to subsequent participants. ETHICS AND
      DISSEMINATION: Ethical approval for the study was granted on 18 February 2013.
      RESULTS: The results of this study will be reported through peer-reviewed
      journals, conference presentations and an internal organisational report. TRIAL
      REGISTRATION NUMBERS: NCT01827735, ISRCTN27852285, DRN767.

PMID- 24898092
TI  - Effect of disulfide crosslinking on thermal transitions and chaperone-like
      activity of human small heat shock protein HspB1.
AB  - Temperature-induced conformational changes of reduced and oxidized HspB1
      crosslinked by disulfide bond between single Cys137 of neighboring monomers were
      analyzed by means of different techniques. Heating of reduced HspB1 was
      accompanied by irreversible changes of Trp fluorescence, whereas oxidized HspB1
      underwent completely reversible changes of fluorescence. Increase of the
      temperature in the range of 20-70  degrees C was accompanied by self-association
      of both reduced and oxidized protein. Further increase of the temperature led to
      formation of heterogeneous mixture of large self-associated complexes of reduced
      HspB1 and to formation of smaller and less heterogeneous complexes of oxidized
      HspB1. Heat-induced changes of oligomeric state of reduced HspB1 were only
      partially reversible, whereas the corresponding changes of oligomeric state of
      oxidized HspB1 were almost completely reversible. Oxidation resulted in decrease
      of chaperone-like activity of HspB1. It is concluded that oxidative stress,
      inducing formation of disulfide bond, can affect stability and conformational
      mobility of human HspB1.

PMID- 24898094
TI  - In vivo characterization of the biodistribution profile of amphipol A8-35.
AB  - Amphipols (APols) are polymeric surfactants that keep membrane proteins (MPs)
      water-soluble in the absence of detergent, while stabilizing them. They can be
      used to deliver MPs and other hydrophobic molecules in vivo for therapeutic
      purposes, e.g., vaccination or targeted delivery of drugs. The biodistribution
      and elimination of the best characterized APol, a polyacrylate derivative called
      A8-35, have been examined in mice, using two fluorescent APols, grafted with
      either Alexa Fluor 647 or rhodamine. Three of the most common injection routes
      have been used, intravenous (IV), intraperitoneal (IP), and subcutaneous (SC).
      The biodistribution has been studied by in vivo fluorescence imaging and by
      determining the concentration of fluorophore in the main organs. Free rhodamine
      was used as a control. Upon IV injection, A8-35 distributes rapidly throughout
      the organism and is found in most organs but the brain and spleen, before being
      slowly eliminated (10-20 days). A similar pattern is observed after IP injection,
      following a brief latency period during which the polymer remains confined to the
      peritoneal cavity. Upon SC injection, A8-35 remains essentially confined to the
      point of injection, from which it is only slowly released. An interesting
      observation is that A8-35 tends to accumulate in fat pads, suggesting that it
      could be used to deliver anti-obesity drugs.

PMID- 24898095
TI  - The effect of fibre source on the numbers of some fibre-degrading bacteria of
      Arabian camel's (Camelus dromedarius) foregut origin.
AB  - The total bacterial community of Fibrobacter succinogenes and Ruminococcus
      flavefaciens in fibre-enriched culture of the foregut contents of 12 adult feral
      camels (Camelus dromedaries) fed on native vegetation in Australia was
      investigated using quantitative PCR. Foregut contents were collected postmortem,
      pooled and filtered before divided into two fractions. One fraction was used for
      extraction of DNA, while the other fraction was inoculated straight away into BM
      10 contained filter paper (FP), cotton thread (CT) or neutral detergent fibre
      (NDF) as the sole carbohydrate sources in Hungate tubes. The tubes were incubated
      anaerobically at 39  degrees C for 1 week. After a near complete degradation of
      the FP and CT and extensive turbidity in the NDF, media subculturing was carried
      out into fresh media tubes. This was repeated twice before genomic DNA was
      extracted and used for quantification of bacteria. Using an absolute
      quantification method, the numbers of cells in 1 ml of each sample ranged from
      4.07 * 10(6) to 2.73 * 10(9) for total bacteria, 1.34 * 10(3) to 2.17 * 10(5) for
      F. succinogenes and 5.78 * 10(1) to 3.53 * 10(4) for R. flavefaciens. The mean
      cell number of F. succinogenes was highest in the FP enrichment medium at
      approximately 107-fold, whereas for the R. flavefaciens targeted primer, the NDF
      enrichment media had the highest mean cell number at approximately 4-fold when
      compared to the rumen content. The data presented here provide evidence of fibre
      type preference by the two main fibre-degrading bacteria and would help us
      understand the interaction between fibre type and fibre-degrading microorganisms,
      which has ramification on camel nutrition at different seasons and environments.

PMID- 24898093
TI  - Factors associated with high burden in caregivers of older adults with cancer.
AB  - BACKGROUND: Older adults with cancer are vulnerable to functional decline, which
      places greater onus on caregivers. Few studies have prospectively examined burden
      in caregivers of older cancer patients. The objective of this study was to
      determine the factors associated with high caregiver burden. METHODS: In total,
      100 caregivers of patients aged >=65 years with cancer, who were recruited at a
      single institution, completed questionnaires gauging their perception of the
      patient's physical, emotional, and social health. The association between these
      items, cancer-related factors, sociodemographic factors, and caregiver burden
      (measured using the Caregiver Strain Index [CSI]) was determined through
      multivariate analysis. RESULTS: The median patient age was 70 years (range, 65-91
      years), 70% of patients had advanced disease, and 98% were receiving treatment.
      Caregivers were mostly women (73%), spouses (68%), and lived with the patient
      (79%). The median amount of care provided was 10 hours per week. The mean CSI
      score (+/- standard deviation) was 3.1 +/- 3.2. Most caregivers (75%) reported
      some burden, with 15% reporting high caregiver burden (CSI score, >=7). In
      multivariate analysis, employed caregivers (odds ratio, 4.5; 95% confidence
      interval, 1.1-18.4; P = .04) and those caring for patients who required more help
      with instrumental activities of daily living (Older Americans Resources and
      Services-Instrumental Activities of Daily Living score, <12 of a possible 14;
      odds ratio, 12.4; 95% confidence interval, 2.4-62.5; P < .001) were more likely
      to experience high caregiver burden (CSI score, >=7). CONCLUSIONS: Caregiver
      burden is common in those who care for older cancer patients. High burden is more
      likely in employed caregivers and in those who care for patients who require
      increased functional assistance. Further studies are needed to determine the
      unique challenges experienced by caregivers of older adults with cancer and
      potential interventions to alleviate burden in these caregivers.

PMID- 24898096
TI  - Value of gadofosveset-enhanced MRI and multiplanar reformatting for selecting
      good responders after chemoradiation for rectal cancer.
AB  - OBJECTIVES: Our primary objective was to evaluate diagnostic performance of
      gadofosveset T1-weighted magnetic resonance imaging (T1W MRI) for discriminating
      between ypT0-2 and ypT3-4 tumours after chemoradiation therapy (CRT) for rectal
      cancer compared with T2W MRI for a general and expert reader. Second objectives
      included assessing the value of multiplanar reformatting (MPR) and interobserver
      agreement. METHODS: A general and expert reader evaluated 49 patients for
      likelihood of ypT0-2 tumour after CRT on T2W, gadofosveset T1W MRI, and
      gadofosveset T1W MRI + T2W MRI. The general reader scored with and without MPR.
      Confidence level scores were used to construct receiver-operating characteristic
      (ROC) curves. Area under the curve (AUC) values and diagnostic parameters were
      calculated and compared. RESULTS: Gadofosveset T1W MRI + T2W MRI showed slightly
      superior sensitivity than T2W MRI for the general but not the expert reader.
      Specificity was higher for the expert on gadofosveset T1W MRI only compared with
      T2W MRI only (100% vs. 82%). MPR did not increase diagnostic performance.
      Interobserver agreement was highest for the combination of gadofosveset-enhanced
      T1W imaging plus T2W MRI. CONCLUSIONS: The sole use or addition of gadofosveset
      enhanced T1W MRI to T2W MRI did not increase significantly diagnostic performance
      for assessing ypT0-2 tumours. Adding gadofosveset-enhanced T1W MRI slightly
      increased sensitivity for the general reader and specificity for the expert
      reader, but this increase was not significant for more accurate clinical decision
      making. MPR did not improve diagnostic performance. KEY POINTS: * ycT restaging
      with MRI in rectal cancer is challenging. * Gadofosveset-enhanced T1W MRI has
      shown promise for nodal restaging. * Gadofosveset-enhanced T1W MRI did not
      significantly increase diagnostic performance for assessing ypT0-2-tumours. *
      Addition of the gadofosveset sequence to T2W MRI slightly increased sensitivity
      for the general reader. * MPR did not improve diagnostic performance of ycT
      staging.

PMID- 24898098
TI  - Simultaneous analysis of seven 2-hydroxy fatty acids as tert-butyldimethylsilyl
      derivatives in plasma by gas chromatography-mass spectrometry.
AB  - An efficient method for the simultaneous analysis of seven 2-hydroxy fatty acids
      (2-HFAs) as tert-butyldimethylsilyl (TBDMS) derivative was developed by gas
      chromatography-mass spectrometry in selected ion monitoring mode. New mass
      spectral data on 2-hydroxycapric, 2-hydroxypalmitic, 2-hydroxystearic and 2
      hydroxybehenic acids as di-TBDMS derivatives for hydroxyl and carboxyl groups
      were built. Under the optimal conditions, the present method showed a good
      correlation coefficient (r >= 0.999) in the range of 0.01-0.5 ug. The precision
      showed low relative standard deviation of <10%, and the accuracy (percentage
      relative error) varied from -5.2 to 0.3 for the seven 2-HFAs studied. Recovery
      rates of all 2-HFAs were  >= 93.2% with good precision. When applied to normal
      human plasma, seven 2-HFAs were positively identified. Therefore, the present
      efficient method will be useful for simultaneous analysis of 2-HFAs in plasma.

PMID- 24898097
TI  - Diffusion-weighted magnetic resonance imaging of breast lesions: the influence of
      different fat-suppression techniques on quantitative measurements and their
      reproducibility.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of different fat
      suppression techniques on quantitative measurements and their reproducibility
      when applied to diffusion-weighted imaging (DWI) of breast lesions. METHODS:
      Twenty-five patients with different types of breast lesions were examined on a
      clinical 1.5-T magnetic resonance imaging (MRI) system. Two diffusion-weighted
      sequences with different fat-suppression methods were applied: one with spectral
      presaturation by inversion recovery (SPIR), and one with short-TI inversion
      recovery (STIR). The acquisition of both sequence variants was repeated with
      modified shim volume. Lesion-to-background contrast (LBC), apparent diffusion
      coefficients (ADC) ADC(0,1000) and ADC(50,1000), and their coefficients of
      variation (CV) were determined. RESULTS: In four patients, the image quality of
      DWI with SPIR was insufficient. In the other 21 patients, 46 regions of interest
      (ROI), including 11 malignant and 35 benign lesions, were analysed. The LBC,
      ADC(0,1000) and ADC(50,1000) values, which did not differ between initial and
      repeated measurements, were significantly higher for STIR than for SPIR. The mean
      CV improved from 10.8 % to 4.0 % (P = 0.0047) for LBC, from 6.3 % to 2.9 % (P =
      0.0041) for ADC(0,1000), and from 6.3 % to 2.6 % (P = 0.0049) for ADC(50,1000).
      CONCLUSION: For STIR compared to SPIR fat suppression, improved lesion
      conspicuity, higher ADC values, and better measurement reproducibility were found
      in breast DWI. KEY POINTS: * Quality of fat suppression influences quantitative
      DWI breast lesion measurements. * In breast DWI, STIR fat suppression worked more
      reliably than SPIR. * Lesion-to-background contrast and its reproducibility were
      significantly higher with STIR fat suppression. * Lesional ADCs and their
      reproducibility were significantly higher with STIR fat suppression.

PMID- 24898099
TI  - Effect of biliary cirrhosis on neurogenic relaxation of rat gastric fundus and
      anococcygeus muscle: role of nitric oxide pathway.
AB  - BACKGROUND: Cirrhosis, associated with a host of hemodynamic abnormalities, could
      affect the gastrointestinal (GI) tract motility. On the other hand, the
      nonadrenergic noncholinergic (NANC) neurotransmission has been shown to play a
      pivotal role in GI tract motility and has been linked with release of nitric
      oxide (NO) on electrical stimulation. In this study, we investigated the effect
      of biliary cirrhosis on the neurogenic relaxation of rat gastric fundus and
      anococcygeus muscle and also the possible role of nitric oxide system in this
      manner. METHODS: Isolated gastric fundus and anococcygeus strips of sham-operated
      and biliary cirrhotic (4 weeks after bile duct ligation) rats were mounted under
      tension in a standard organ bath. Electrical stimulation was applied to obtain
      NANC-mediated relaxations in precontracted gastric fundus and anococcygeus
      muscle. The neurogenic relaxations were examined in the presence of different
      doses of NO synthase inhibitor, N (w)-Nitro-L-Arginine Methyl Ester (L-NAME). The
      concentration-dependent relaxant responses to the NO donor sodium nitroprusside
      were also evaluated. RESULTS: The neurogenic relaxation of both gastric fundus
      and anococcygeus muscle was significantly (P < 0.001) increased in cirrhotic
      animals. L-NAME (0.03-1,000 uM) inhibited relaxations in both groups in a dose
      dependent manner (P < 0.001), but cirrhotic groups were more resistant to the
      inhibitory effects of L-NAME (P < 0.01). Sodium nitroprusside-mediated
      relaxations were similar in two groups. CONCLUSIONS: This study for the first
      time demonstrated that cirrhosis increases the NO-mediated neurogenic relaxation
      of both rat gastric fundus and anococcygeus muscle, suggesting a crucial role for
      the neurogenic NO in the pathophysiology of disturbed GI motility in cirrhosis.

PMID- 24898100
TI  - Use of tenofovir disoproxil fumarate in highly viremic, hepatitis B mono-infected
      pregnant women.
AB  - BACKGROUND: Antiviral therapy in addition to immunoprophylaxis at birth has been
      shown to further reduce perinatal transmission of hepatitis B virus (HBV) in
      highly viremic women. AIMS: The aim of this study was to describe the use of
      tenofovir disoproxil fumarate (TDF) prophylaxis to reduce maternal HBV DNA levels
      and potentially vertical transmission in highly viremic women. METHODS: After
      receiving IRB approval, we performed a retrospective chart review of mothers
      positive for hepatitis B surface antigen (HBsAg) who delivered between 2009 and
      2012. We identified women with HBV DNA levels >=6 log copies/mL who were treated
      with TDF in pregnancy. RESULTS: There were 22 women identified. The majority were
      of Micronesian ethnicity. All were negative for hepatitis C antibody and HIV
      infection. The median gestational age of TDF initiation was 31 weeks with a
      median duration of treatment of 45 days. There was a reduction in median HBV DNA
      levels from baseline 9.0 +/- 2.0 to 5.4 +/- 1.1 log copies/mL after treatment.
      There were five (22.7 %) preterm deliveries and five (22.7 %) cesarean
      deliveries. All infants received immunoprophylaxis at birth. Postnatal HBsAg
      testing at 9-12 months was available for 13 infants, 12 of which were negative.
      There was one case of perinatal transmission. CONCLUSIONS: This is the second
      published case series to date on the use of TDF prophylaxis in HBV mono-infected,
      highly viremic mothers. This series suggests the use of TDF in pregnancy reduces
      maternal HBV DNA levels and is well tolerated.

PMID- 24898101
TI  - Early oral antibiotic switch compared with conventional intravenous antibiotic
      therapy for acute cholangitis with bacteremia.
AB  - BACKGROUND: Biliary decompression with antibiotic therapy is the mainstay
      treatment for acute cholangitis with bacteremia. A few studies have been
      conducted to investigate the optimal duration and route of antibiotic therapy in
      biliary tract infection with bacteremia. METHODS: Patients with acute cholangitis
      with bacteremia who achieved successful biliary drainage were randomly assigned
      to an early oral antibiotic switch group (group A, n = 29) and a conventional
      intravenous antibiotics group (group B, n = 30). Patients were discharged when
      they were afebrile over 2 days after oral antibiotic switch and showed
      consecutive improvement in the laboratory index. They were followed up and
      assessed at 30 days after diagnosis to evaluate the eradication of bacteria,
      recurrence of acute cholangitis, and 30-day mortality rate. RESULTS: There were
      no statistically significant differences between the two groups in baseline
      characteristics, clinical and laboratory index, severity of acute cholangitis,
      bacteria isolated from blood cultures, and clinical outcomes. The rate of
      eradication of bacteria was 93.1 % in group A and 93.3 % in group B, respectively
      (p = 0.97). Using non-inferiority tests, the rate of eradication of bacteria in
      group A was not inferior to that in group B (95 % CI -0.13 to 0.14, p = 0.97).
      There was no statistically significant difference in the recurrence of acute
      cholangitis and a 30-day mortality rate between the two groups. CONCLUSIONS:
      Early switch to oral antibiotic therapy following adequate biliary drainage for
      treatment of acute cholangitis with bacteremia was not inferior to conventional
      10-day intravenous antibiotic therapy.

PMID- 24898102
TI  - The interpretive power of infraorbital foramen area in making dietary inferences
      in extant apes.
AB  - The infraorbital foramen (IOF) is located below the orbit and transmits the
      sensory infraorbital nerve (ION) to mechanoreceptors located throughout the
      maxillary region. The size of the IOF correlates with the size of the ION; thus,
      the IOF appears to indicate relative touch sensitivity of maxillary region. In
      primates, IOF size correlates well with diet. Frugivores have relatively larger
      IOFs than folivores or insectivores because fruit handling/processing requires
      increased touch sensitivity. However, it is unknown if the IOF can be used to
      detect subtle dietary differences among closely related hominoid species.
      Hominoids are traditionally grouped into broad dietary categories, despite the
      fact that hominoid diets are remarkably diverse. This study examines whether
      relative IOF size is capable of differentiating among the dietary preferences of
      closely related species with overlapping, yet divergent diets. We measured IOF
      area in Hylobates lar, Symphalangus syndactulus, Pongo pygmaeus spp., Pan
      troglodytes, Gorilla gorilla, Gorilla beringei graueri, and Gorilla beringei
      beringei. We classified each species as a dedicated folivore, mixed
      folivore/frugivore, soft object frugivore, or hard object frugivore. The IOF is
      documented to be larger in more frugivorous species and smaller in more
      folivorous taxa. Interestingly, G.b. beringei, had the largest relative IOF of
      any gorilla, despite being a dedicated folivore. G.b. beringei does have unique
      food processing behavior that relies heavily on maxillary mechanoreception, thus
      this finding is not entirely unsupported behaviorally. The results of this study
      provide evidence that the IOF is an informative feature in interpretations of
      fossil apes.

PMID- 24898103
TI  - Economic analysis of use of pessary to prevent preterm birth in women with
      multiple pregnancy (ProTWIN trial).
AB  - OBJECTIVE: To assess the cost-effectiveness of a cervical pessary to prevent
      preterm delivery in women with a multiple pregnancy. METHODS: The study design
      comprised an economic analysis of data from a randomized clinical trial
      evaluating cervical pessaries (ProTWIN). Women with a multiple pregnancy were
      included and an economic evaluation was performed from a societal perspective.
      Costs were estimated between the time of randomization and 6 weeks postpartum.
      The prespecified subgroup of women with a cervical length (CL) < 25(th) centile
      (< 38 mm) was analyzed separately. The primary endpoint was poor perinatal
      outcome occurring up to 6 weeks postpartum. Direct medical costs and health
      outcomes were estimated and incremental cost-effectiveness ratios for costs to
      prevent one poor outcome were calculated. RESULTS: Mean costs in the pessary
      group (n = 401) were ? 21,783 vs ? 21,877 in the group in which no pessary was
      used (n = 407) (difference, -? 94; 95% CI, -? 5975 to ? 5609). In the
      prespecified subgroup of women with a CL < 38 mm we demonstrated a significant
      reduction in poor perinatal outcome (12% vs 29%; RR, 0.40; 95% CI, 0.19-0.83).
      Mean costs in the pessary group (n = 78) were ? 25,141 vs ? 30,577 in the no
      pessary group (n = 55) (difference, -? 5436 (95% CI, -? 11,001 to ? 1456). In
      women with a CL < 38 mm, pessary treatment was the dominant strategy (more
      effective and less costly) with a probability of 94%. CONCLUSION: Cervical
      pessaries in women with a multiple pregnancy involve costs comparable to those in
      women without pessary treatment. However, in women with a CL < 38 mm, treatment
      with a cervical pessary appears to be highly cost-effective.

PMID- 24898104
TI  - The effect of cardiovascular credentialed pharmacists on process measures and
      outcomes in myocardial infarction and heart failure.
AB  - OBJECTIVE: The purpose of this study was to determine if institutions with
      inpatient cardiovascular credentialed pharmacists exhibit improved quality
      measures for acute myocardial infarction (AMI) and heart failure (HF) care
      compared with institutions without inpatient cardiovascular credentialed
      pharmacists. METHODS: We conducted a multicenter, retrospective, cross-sectional,
      matched case-control study. Hospitals with at least one Added Qualification in
      Cardiology (AQCV) inpatient pharmacist were included in the case group. Each case
      group hospital was matched to hospitals without an AQCV pharmacist by region,
      number of cardiovascular discharges, and teaching hospital designation in a 1:3
      ratio (case:control). The 34 AQCV hospitals were matched to 102 non-AQCV
      hospitals. The proportions of discharges meeting HF and AMI process of care
      measures and 30-day outcomes (readmission and mortality) for each hospital were
      determined from public data and compared between the case and control groups.
      RESULTS: Hospitals with AQCV pharmacists performed better on process of care
      measures than hospitals without AQCV pharmacists (odds ratio 1.41, 95% confidence
      interval 1.25-1.58, p<0.0001, p<0.001 for heterogeneity), which was mainly driven
      by the aspirin on discharge for AMI and angiotensin-converting enzyme inhibitor
      or angiotensin receptor blocker on discharge for HF measures. No differences were
      observed between the groups for either readmission or mortality at 30 days.
      CONCLUSIONS: Hospitals that used inpatient AQCV pharmacists performed better on
      process of care measures than hospitals that do not use inpatient AQCV
      pharmacists. However, improvements in process of care performance measures
      observed in AQCV hospitals did not translate into improved 30-day clinical
      outcomes.

PMID- 24898105
TI  - The therapeutic effect of UDCA is a factor in determining the prognosis of
      primary biliary cirrhosis.

PMID- 24898107
TI  - Comparative human and rat "neurosphere assay" for developmental neurotoxicity
      testing.
AB  - The developing nervous system is highly vulnerable to the adverse effects of
      chemical agents. Currently, there is an increasing need for testing and
      regulating chemical compounds in general use and, due to the lack of available
      data, to identify those which are developmental neurotoxicants. In this context,
      alternative testing strategies are needed in order to allow fast and cost
      efficient screening and to reduce the number of animal experiments usually
      required. In this unit we present an in vitro three-dimensional model for
      developmental neurotoxicity screening based on human and rat neural progenitor
      cells. This model enables the detection of disturbances in basic processes of
      brain development, such as proliferation, migration, differentiation and
      apoptosis, and allows the distinction of these specific disturbances from general
      cytotoxicity. Furthermore, the comparison of human and rat data provides useful
      insights into species differences for toxicodynamics of compounds contributing to
      human risk assessment of developmental neurotoxicants.

PMID- 24898106
TI  - Medication overuse in children and adolescents.
AB  - Medication overuse is not uncommon among children and adolescents with primary
      headache disorders. Medication overuse in adults is associated with increased
      headache frequency and reduced effectiveness of acute and preventive medications.
      These issues probably exist in children. While withdrawal of overused medications
      is generally recommended, it may not result in improved headache frequency in all
      patients. This review summarizes what is known about predicting the response to
      medication withdrawal. Strategies for managing children and adolescents with
      medication overuse are also offered.

PMID- 24898109
TI  - Asymmetric cascade reaction to allylic sulfonamides from allylic alcohols by
      palladium(II)/base-catalyzed rearrangement of allylic carbamates.
AB  - A regio- and enantioselective tandem reaction is reported capable of directly
      transforming readily accessible achiral allylic alcohols into chiral sulfonyl
      protected allylic amines. The reaction is catalyzed by the cooperative action of
      a chiral ferrocene palladacycle and a tertiary amine base and combines high step
      economy with operational simplicity (e.g. no need for inert-gas atmosphere or
      catalyst activation). Mechanistic studies support a Pd(II)-catalyzed [3,3]
      rearrangement of allylic carbamates--generated in situ from the allylic alcohol
      and an isocyanate--as the key step, which is followed by a decarboxylation.

PMID- 24898108
TI  - Bosentan as rescue treatment in refractory hypoxemia and pulmonary hypertension
      in a patient with ARDS and H7N9 influenza virus infection.

PMID- 24898110
TI  - Optimising expression of the recombinant fusion protein biopesticide omega
      hexatoxin-Hv1a/GNA in Pichia pastoris: sequence modifications and a simple method
      for the generation of multi-copy strains.
AB  - Production of recombinant protein bio-insecticides on a commercial scale can only
      be cost effective if host strains with very high expression levels are available.
      A recombinant fusion protein containing an arthropod toxin, omega-hexatoxin-Hv1a,
      (from funnel web spider Hadronyche versuta) linked to snowdrop lectin (Galanthus
      nivalis agglutinin; GNA) is an effective oral insecticide and candidate
      biopesticide. However, the fusion protein was vulnerable to proteolysis during
      production in the yeast Pichia pastoris. To prevent proteolysis, the Hv1a/GNA
      fusion expression construct was modified by site-directed mutagenesis to remove a
      potential Kex2 cleavage site at the C-terminus of the Hv1a peptide. To obtain a
      high expressing clone of P. pastoris to produce recombinant Hv1a/GNA, a
      straightforward method was used to produce multi-copy expression plasmids, which
      does not require multiple integrations to give clones of P. pastoris containing
      high copy numbers of the introduced gene. Removal of the Kex2 site resulted in
      increased levels of intact fusion protein expressed in wild-type P. pastoris
      strains, improving levels of intact recombinant protein recoverable.
      Incorporation of a C-terminal (His)6 tag enabled single step purification of the
      fusion protein. These modifications did not affect the insecticidal activity of
      the recombinant toxin towards lepidopteran larvae. Introduction of multiple
      expression cassettes increased the amount of secreted recombinant fusion protein
      in a laboratory scale fermentation by almost tenfold on a per litre of culture
      basis. Simple modifications in the expression construct can be advantageous for
      the generation of high expressing P. pastoris strains for production of a
      recombinant protein, without altering its functional properties.

PMID- 24898112
TI  - Asymmetrically-gated graphene self-switching diodes as negative differential
      resistance devices.
AB  - We present an asymmetrically-gated Graphene Self-Switching Diode (G-SSD) as a new
      negative differential resistance (NDR) device, and study its transport properties
      using nonequilibrium Green's function (NEGF) formalism and the Extended Huckel
      (EH) method. The device exhibits a new NDR mechanism, in which a very small
      quantum tunnelling current is used to control a much-larger channel conduction
      current, resulting in a very pronounced NDR effect. This NDR effect occurs at low
      bias voltages, below 1 V, and results in a very high current peak in the MUA
      range and a high peak-to-valley current ratio (PVCR) of 40. The device has an
      atomically-thin structure with sub-10 nm dimensions, and does not require any
      doping or external gating. These results suggest that the device has promising
      potential in applications such as high frequency oscillators, memory devices, and
      fast switches. 

PMID- 24898111
TI  - Maternal exposure to methotrexate and birth defects: a population-based study.
AB  - Methotrexate is an anti-folate medication that is associated with increased risk
      of multiple birth defects. Using data from the National Birth Defects Prevention
      Study, a case-control study of major birth defects in the United States, we
      examined mothers exposed to methotrexate. The study population included mothers
      of live-born infants without major birth defects (controls) and mothers of
      fetuses or infants with a major birth defect (cases), with expected dates of
      delivery between October 1997 and December 2009. Mothers of cases and controls
      were asked detailed questions concerning pregnancy history, demographic
      information, and exposures in a telephone interview. Approximately 0.06% (n =
      16/27,623) of case and 0.04% (n = 4/10,113) of control mothers reported exposure
      to methotrexate between 3 months prior to conception through the end of
      pregnancy. Of the 16 case infants, 11 (68.8%) had a congenital heart defect
      (CHD). The observed CHDs included atrial septal defects, tetralogy of Fallot,
      valvar pulmonary stenosis, ventricular septal defects (VSDs), and total anomalous
      pulmonary venous return. One case infant had microtia in addition to a VSD and
      another had VACTER association. Exposed cases without a CHD had one of the
      following birth defects: cleft palate, hypospadias, congenital diaphragmatic
      hernia, or craniosynostosis. Based on a limited number of methotrexate-exposed
      mothers, our findings support recent case reports suggesting an association
      between early pregnancy exposure to methotrexate and CHDs. Because of the rarity
      of maternal periconceptional exposure to methotrexate, long-term, population
      based case-control studies are needed to confirm these findings and better
      evaluate the association between methotrexate and birth defects.

PMID- 24898113
TI  - Using analogy role-play activity in an undergraduate biology classroom to show
      central dogma revision.
AB  - For the study of biology in an undergraduate classroom, a classroom exercise was
      developed: an analogy role-play to learn mechanisms of gene transcription and
      protein translation (central dogma). To develop the central dogma role-play
      exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress
      hanger, and amino acids using Lego(r) blocks (Lego System A/S, Denmark). Students
      were studying in the course of mathematics, physics, or chemistry, so biology was
      not among their usual studies. In this exercise, students perform the central
      dogma role-play and respectively act out nuclear matrix proteins, a transcription
      factor, an RNA polymerase II, an mRNA transport protein, nuclear pore proteins, a
      large ribosomal subunit, a small ribosomal subunit, and several amino-acyl tRNA
      synthetases. Questionnaire results obtained after the activity show that this
      central dogma role-play analogy holds student interest in the practical molecular
      biological processes of transcription and translation.

PMID- 24898114
TI  - Monte Carlo simulation of novel breast imaging modalities based on coherent x-ray
      scattering.
AB  - We present upgraded versions of MC-GPU and penEasy_Imaging, two open-source Monte
      Carlo codes for the simulation of radiographic projections and CT, that have been
      extended and validated to account for the effect of molecular interference in the
      coherent x-ray scatter. The codes were first validation by comparison between
      simulated and measured energy dispersive x-ray diffraction (EDXRD) spectra. A
      second validation was by evaluation of the rejection factor of a focused anti
      scatter grid. To exemplify the capabilities of the new codes, the modified MC-GPU
      code was used to examine the possibility of characterizing breast tissue
      composition and microcalcifications in a volume of interest inside a whole breast
      phantom using EDXRD and to simulate a coherent scatter computed tomography (CSCT)
      system based on first generation CT acquisition geometry. It was confirmed that
      EDXRD and CSCT have the potential to characterize tissue composition inside a
      whole breast. The GPU-accelerated code was able to simulate, in just a few hours,
      a complete CSCT acquisition composed of 9758 independent pencil-beam projections.
      In summary, it has been shown that the presented software can be used for fast
      and accurate simulation of novel breast imaging modalities relying on scattering
      measurements and therefore can assist in the characterization and optimization of
      promising modalities currently under development. 

PMID- 24898115
TI  - Design and development of a mobile-based system for supporting emergency triage
      decision making.
AB  - Emergency care for mass casualty incidents is a sophisticated multi-participant
      process. To manage this process effectively, many information systems have been
      proposed. However, their performance in improving the efficiency and accuracy of
      patient triage is not satisfactory. This paper is concerned with the development
      of a mobile-based system for supporting emergency triage in the emergency care
      process for mass casualty incidents. This system collects the patient's emergency
      data throughout the whole emergency care process through a mobile application and
      data transfer mechanism. Using a Cox proportional hazard model, the system has
      the capacity to present the survival curve to the triage officer, helping him/her
      to make triage and transportation decisions. This system offers an alternative
      injury assessment tool based on the vital signs data of the injury patient. With
      the help of this system, the triage officer can more directly and comprehensively
      learn about each patient's situation and deterioration without additional
      operations at the incident site. 

PMID- 24898117
TI  - Doppler evaluation of ocular vessels in patients with primary open angle
      glaucoma.
AB  - PURPOSE: To assess ocular blood flow in patients with primary open angle glaucoma
      (POAG) with or without progressive visual field loss in comparison with controls.
      METHODS: Color Doppler imaging was performed on 78 eyes with established POAG (25
      with progressive visual field loss and 53 with stable visual field) and 78
      control eyes. Peak systolic velocity, end diastolic velocity (EDV), and
      resistance index (RI) were measured in the ophthalmic (OA), central-retinal, and
      medial and lateral posterior ciliary arteries. RESULTS: Peak systolic velocity
      and EDV were lower and RI was higher in the ocular vessels of eyes with POAG (p <
      .01). The OA and medial posterior ciliary arteries RI was higher, and the OA EDV
      was lower in glaucomatous eyes with progressive than with stable visual field
      loss. The receiver operating characteristic curve showed the optimal cutoff RI to
      be 0.847. CONCLUSIONS: Ocular blood flow appears compromised in eyes with POAG,
      particularly in those with progressive visual field loss.

PMID- 24898118
TI  - The roles of associative and executive processes in creative cognition.
AB  - How does the mind produce creative ideas? Past research has pointed to important
      roles of both executive and associative processes in creative cognition. But such
      work has largely focused on the influence of one ability or the other-executive
      or associative-so the extent to which both abilities may jointly affect creative
      thought remains unclear. Using multivariate structural equation modeling, we
      conducted two studies to determine the relative influences of executive and
      associative processes in domain-general creative cognition (i.e., divergent
      thinking). Participants completed a series of verbal fluency tasks, and their
      responses were analyzed by means of latent semantic analysis (LSA) and scored for
      semantic distance as a measure of associative ability. Participants also
      completed several measures of executive function-including broad retrieval
      ability (Gr) and fluid intelligence (Gf). Across both studies, we found
      substantial effects of both associative and executive abilities: As the average
      semantic distance between verbal fluency responses and cues increased, so did the
      creative quality of divergent-thinking responses (Study 1 and Study 2). Moreover,
      the creative quality of divergent-thinking responses was predicted by the
      executive variables-Gr (Study 1) and Gf (Study 2). Importantly, the effects of
      semantic distance and the executive function variables remained robust in the
      same structural equation model predicting divergent thinking, suggesting unique
      contributions of both constructs. The present research extends recent
      applications of LSA in creativity research and provides support for the notion
      that both associative and executive processes underlie the production of novel
      ideas. 

PMID- 24898119
TI  - People use the memory for past-test heuristic as an explicit cue for judgments of
      learning.
AB  - When people estimate their memory for to-be-learned material over multiple study
      test trials, they tend to base their judgments of learning (JOLs) on their test
      performance for those materials on the previous trial. Their use of this
      information-known as the memory for past-test (MPT) heuristic-is believed to be
      responsible for improvements in the relative accuracy (resolution) of people's
      JOLs across learning trials. Although participants seem to use past-test
      information as a major basis for their JOLs, little is known about how learners
      translate this information into a judgment of learning. Toward this end, in two
      experiments, we examined whether participants factored past-test performance into
      their JOLs in either an explicit, theory-based way or an implicit way. To do so,
      we had one group of participants (learners) study paired associates, make JOLs,
      and take a test on two study-test trials. Other participants (observers) viewed
      learners' protocols and made JOLs for the learners. Presumably, observers could
      only use theory-based information to make JOLs for the learners, which allowed us
      to estimate the contribution of explicit and implicit information to learners'
      JOLs. Our analyses suggest that all participants factored simple past-test
      performance into their JOLs in an explicit, theory-based way but that this
      information made limited contributions to improvements in relative accuracy
      across trials. In contrast, learners also used other privileged, implicit
      information about their learning to inform their judgments (that observers had no
      access to) that allowed them to achieve further improvements in relative accuracy
      across trials.

PMID- 24898120
TI  - Human papillomavirus-related cell cycle markers can predict survival outcomes
      following a transoral lateral oropharyngectomy for tonsillar squamous cell
      carcinoma.
AB  - OBJECTIVES: To identify the prognostic implications of human papillomavirus (HPV)
      related cell cycle marker profiles in patients who have received a transoral
      lateral oropharyngectomy (TLO) as a primary treatment for tonsillar squamous cell
      carcinoma (TSCC). PATIENTS AND METHODS: Immunohistochemical profiles of HPV
      related cell cycle markers, including p16, pRb, cyclin D1, p53, and the HPV DNA
      status of 42 consecutive TSCC patients who underwent TLO-based treatments were
      analyzed. The prognostic value of each marker was evaluated. RESULTS: Univariate
      analysis indicated that high p16, low pRb, and low p53 expression levels are
      significantly associated with a good disease-free and overall survival outcome.
      Clinicopathological parameters and the HPV DNA status did not show prognostic
      significance. When adjusted for age, overall stage and treatment strategy, a high
      p16 and low pRb level remained an effective prognostic marker for good survival
      outcomes. A high p16/low pRb combination showed superior survival prediction
      ability over high p16 or low pRb alone. CONCLUSION: HPV-related cell cycle
      markers may also be good indicators for predicting survival after TLO for TSCC.
      The de-escalation TLO surgery approach would be more effective if performed under
      the stringent guidance of these markers.

PMID- 24898121
TI  - Mucosal dominant-type pemphigus vulgaris associated with gastrointestinal stromal
      tumor.

PMID- 24898124
TI  - Chinese tobacco companies' social media marketing strategies.

PMID- 24898122
TI  - An ultra-high density bin-map for rapid QTL mapping for tassel and ear
      architecture in a large F2 maize population.
AB  - BACKGROUND: Understanding genetic control of tassel and ear architecture in maize
      (Zea mays L. ssp. mays) is important due to their relationship with grain yield.
      High resolution QTL mapping is critical for understanding the underlying
      molecular basis of phenotypic variation. Advanced populations, such as
      recombinant inbred lines, have been broadly adopted for QTL mapping; however,
      construction of large advanced generation crop populations is time-consuming and
      costly. The rapidly declining cost of genotyping due to recent advances in next
      generation sequencing technologies has generated new possibilities for QTL
      mapping using large early generation populations. RESULTS: A set of 708 F2
      progeny derived from inbreds Chang7-2 and 787 were generated and genotyped by
      whole genome low-coverage genotyping-by-sequencing method (average 0.04*). A
      genetic map containing 6,533 bin-markers was constructed based on the parental
      SNPs and a sliding-window method, spanning a total genetic distance of 1,396 cM.
      The high quality and accuracy of this map was validated by the identification of
      two well-studied genes, r1, a qualitative trait locus for color of silk
      (chromosome 10) and ba1 for tassel branch number (chromosome 3). Three traits of
      tassel and ear architecture were evaluated in this population, a total of 10 QTL
      were detected using a permutation-based-significance threshold, seven of which
      overlapped with reported QTL. Three genes (GRMZM2G316366, GRMZM2G492156 and
      GRMZM5G805008) encoding MADS-box domain proteins and a BTB/POZ domain protein
      were located in the small intervals of qTBN5 and qTBN7 (~800 Kb and 1.6 Mb in
      length, respectively) and may be involved in patterning of tassel architecture.
      The small physical intervals of most QTL indicate high-resolution mapping is
      obtainable with this method. CONCLUSIONS: We constructed an ultra-high-dentisy
      linkage map for the large early generation population in maize. Our study
      provides an efficient approach for fast detection of quantitative loci
      responsible for complex trait variation with high accuracy, thus helping to
      dissect the underlying molecular basis of phenotypic variation and accelerate
      improvement of crop breeding in a cost-effective fashion.

PMID- 24898125
TI  - Diversity of Cercopithifilaria species in dogs from Portugal.
AB  - BACKGROUND: Filarioids belonging to the genus Cercopithifilaria (Spirurida:
      Onchocercidae) have been described in dogs in association with Rhipicephalus
      sanguineus group ticks, which act as their biological vectors. This study
      represents the first investigation on Cercopithifilaria spp. in dogs from
      Portugal. FINDINGS: Dogs (n=102) from the Algarve region (south of Portugal) were
      sampled by skin snip collection and tissues were left to soak overnight in saline
      solution. Sediments were observed under a light microscope and the detected
      microfilariae identified according to their morphology. Twenty-four dogs (23.5%)
      were found infected with at least one species of Cercopithifilaria, namely C.
      bainae (9.8%), C. grassii (3.9%) and Cercopithifilaria sp. II sensu Otranto et
      al., 2013 (13.7%). Results were confirmed by molecular amplification of partial
      cytochrome c oxidase subunit I and 12S rRNA genes and sequence analysis. Co
      infections with more than one Cercopithifilaria species were detected in 3.9% of
      the animals. CONCLUSIONS: This is the first report of Cercopithifilaria spp. in
      dogs from Portugal. The estimated level of infection with C. bainae, C. grassii
      and Cercopithifilaria sp. II suggests that these filarioids are prevalent in the
      canine population of southern Portugal.

PMID- 24898123
TI  - Risk factors for recurrent Clostridium difficile infection (CDI) hospitalization
      among hospitalized patients with an initial CDI episode: a retrospective cohort
      study.
AB  - BACKGROUND: Recurrent Clostridium difficile infection (rCDI) is observed in up to
      25% of patients with an initial CDI episode (iCDI). We assessed risk factors for
      rCDI among patients hospitalized with iCDI. METHODS: We performed a retrospective
      cohort study at Barnes-Jewish Hospital from 1/1/03 to 12/31/09. iCDI was defined
      as a positive toxin assay for C. difficile with no CDI in previous 60 days, and
      rCDI as a repeat positive toxin <=42 days of stopping iCDI treatment. Three
      demographic, 13 chronic and 12 acute disease characteristics, and 21 processes of
      care were assessed for association with rCDI. Cox modeling identified independent
      risk factors for rCDI. RESULTS: 425 (10.1%) of 4,200 patients enrolled developed
      rCDI. Of the eight risk factors for rCDI on multivariate analyses, the strongest
      three were 1) high-risk antimicrobials following completion of iCDI treatment (HR
      2.95, 95% CI 2.25-3.86), 2) community-onset healthcare-associated iCDI (HR 1.80,
      95% CI 1.41-2.29) and 3) fluoroquinolones after completion of iCDI treatment (HR
      1.56, 95% CI 1.63-2.08). Other risk factors included gastric acid suppression,
      >=2 hospitalizations within prior 60 days, age, and IV vancomycin after iCDI
      treatment ended. CONCLUSIONS: The rCDI rate was 10.1%. Recognizing such
      modifiable risk factors as certain antimicrobial treatments and gastric acid
      suppression may help optimize prevention efforts.

PMID- 24898126
TI  - Regulation of age-related structural integrity in neurons by protein with tau
      like repeats (PTL-1) is cell autonomous.
AB  - PTL-1 is the sole homolog of the MAP2/MAP4/tau family in Caenorhabditis elegans.
      Accumulation of tau is a pathological hallmark of neurodegenerative diseases such
      as Alzheimer's disease. Therefore, reducing tau levels has been suggested as a
      therapeutic strategy. We previously showed that PTL-1 maintains age-related
      structural integrity in neurons, implying that excessive reduction in the levels
      of a tau-like protein is detrimental. Here, we demonstrate that the regulation of
      neuronal ageing by PTL-1 occurs via a cell-autonomous mechanism. We re-expressed
      PTL-1 in a null mutant background using a pan-neuronal promoter to show that PTL
      1 functions in neurons to maintain structural integrity. We next expressed PTL-1
      only in touch neurons and showed rescue of the neuronal ageing phenotype of ptl-1
      mutant animals in these neurons but not in another neuronal subset, the ventral
      nerve cord GABAergic neurons. Knockdown of PTL-1 in touch neurons also resulted
      in premature neuronal ageing in these neurons but not in GABAergic neurons.
      Additionally, expression of PTL-1 in touch neurons alone was unable to rescue the
      shortened lifespan observed in ptl-1 mutants, but pan-neuronal re-expression
      restored wild-type longevity, indicating that, at least for a specific group of
      mechanosensory neurons, premature neuronal ageing and organismal ageing can be
      decoupled. 

PMID- 24898128
TI  - Functional PEG-PAMAM-tetraphosphonate capped NaLnF4 nanoparticles and their
      colloidal stability in phosphate buffer.
AB  - Developing surface coatings for NaLnF4 nanoparticles (NPs) that provide long-term
      stability in solutions containing competitive ions such as phosphate remains
      challenging. An amine-functional polyamidoamine tetraphosphonate (NH2-PAMAM-4P)
      as a multidentate ligand for these NPs has been synthesized and characterized as
      a ligand for the surface of NaGdF4 and NaTbF4 nanoparticles. A two-step ligand
      exchange protocol was developed for introduction of the NH2-PAMAM-4P ligand on
      oleate-capped NaLnF4 NPs. The NPs were first treated with methoxy-poly(ethylene
      glycol)-monophosphoric acid (M(n) = 750) in tetrahydrofuran. The mPEG750-OPO3
      capped NPs were stable colloidal solutions in water, where they could be ligand
      exchanged with NH2-PAMAM-4P. The surface amine groups on the NPs were available
      for derivatization to attach methoxy-PEG (M(n) = 2000) and biotin-terminated PEG
      (M(n) = 2000) chains. The surface coverage of ligands on the NPs was examined by
      thermal gravimetric analysis, and by a HABA analysis for biotin-containing NPs.
      Colloidal stability of the NPs was examined by dynamic light scattering. NaGdF4
      and NaTbF4 NPs capped with mPEG2000-PAMAM-4P showed colloidal stability in DI
      water and in phosphate buffer (10 mM, pH 7.4). A direct comparison with NaTbF4
      NPs capped with a mPEG2000-lysine-based tetradentate ligand that we reported
      previously (Langmuir 2012, 28, 12861-12870) showed that both ligands provided
      long-term stability in phosphate buffer, but that the lysine-based ligand
      provided better stability in phosphate-buffered saline.

PMID- 24898127
TI  - Anorexia nervosa and bone.
AB  - Anorexia nervosa (AN) is a condition of severe low weight that is associated with
      low bone mass, impaired bone structure, and reduced bone strength, all of which
      contribute to increased fracture risk. Adolescents with AN have decreased rates
      of bone accrual compared with normal-weight controls, raising additional concerns
      of suboptimal peak bone mass and future bone health in this age group. Changes in
      lean mass and compartmental fat depots, and hormonal alterations secondary to
      nutritional factors contribute to impaired bone metabolism in AN. The best
      strategy to improve bone density is to regain weight and menstrual function. Oral
      estrogen-progesterone combinations are not effective in increasing bone density
      in adults or adolescents with AN, and transdermal testosterone replacement is not
      effective in increasing bone density in adult women with AN. However,
      physiological estrogen replacement as transdermal estradiol with cyclic
      progesterone does increase bone accrual rates in adolescents with AN to
      approximate that in normal-weight controls, leading to a maintenance of bone
      density Z-scores. A recent study has shown that risedronate increases bone
      density at the spine and hip in adult women with AN. However, bisphosphonates
      should be used with great caution in women of reproductive age, given their long
      half-life and potential for teratogenicity, and should be considered only in
      patients with low bone density and clinically significant fractures when non
      pharmacological therapies for weight gain are ineffective. Further studies are
      necessary to determine the best therapeutic strategies for low bone density in
      AN. 

PMID- 24898129
TI  - Nationwide trends in pneumonia hospitalization rates and mortality, Denmark 1997
      2011.
AB  - OBJECTIVE: To provide up-to-date population-based data on nationwide trends in
      pneumonia hospitalization rates and associated 30-day mortality. METHODS: Using
      medical databases we identified all in-hospital episodes of pneumonia between
      1997 and 2011. We computed age- and sex-standardized hospitalization rates of
      total and first-time pneumonia-related hospitalization and adjusted 30-day
      mortality rates by calendar year. RESULTS: Among 552,528 pneumonia-related
      hospitalizations in Denmark between 1997 and 2011, 385,985 (69.9%) were first
      time events. Total pneumonia hospitalizations increased by 63%, from 4.96 per
      1000 population in 1997 to 8.09 in 2011. Rates of first-time pneumonia per 1000
      population increased by 33%, from 3.99 in 1997 to 5.31 in 2011. Pneumonia rates
      stabilized in the mid-00s but primary pneumonia rates increased 16% from 2008 to
      2011, most notably among children and young adults. In patients aged >=80 years
      the rate of hospitalizations with secondary pneumonia more than doubled during
      the study period. Average 30-day mortality remained stable at 13%, but increased
      slightly over time in patients aged >=80 years. CONCLUSIONS: In an era of smoking
      cessation and vaccination efforts, pneumonia hospitalization rates are
      continuously increasing, largely driven by secondary diagnoses and recurrent
      pneumonia episodes in elderly patients. Thirty-day mortality remains persistently
      high.

PMID- 24898130
TI  - Vaccination scar, skin lesion, and tattoo design.

PMID- 24898132
TI  - Anti-Mullerian hormone and insulin resistance in polycystic ovary syndrome.
AB  - INTRODUCTION: Polycystic ovary syndrome (PCOS) is a prevalent disease affecting
      women of reproductive age. It may be associated with metabolic disorders such as
      insulin resistance (IR) and obesity. The anti-Mullerian hormone (AMH) levels seem
      to be higher in patients with PCOS. OBJECTIVE: The present study was designed to
      evaluate the association between AMH and insulin in women with PCOS with and
      without IR. METHODS: Cross-sectional study, including 86 patients, selected and
      divided into three groups: Group A: 26 women with PCOS and IR; Group B: 30 women
      with PCOS and without IR; and Group C: 30 controls without PCOS. RESULTS: We
      found significant difference between serum AMH levels in the group of women with
      PCOS and without IR when compared to the control group, thus showing that PCOS
      and IR play an important role in elevating the levels of this hormone. When the
      groups were compared with each other following adjustment for BMI, serum AMH
      levels were significantly higher in the group of women with PCOS and IR.
      CONCLUSION: AMH levels are significantly higher in patients with PCOS,
      particularly in those women with PCOS and IR. Nevertheless, larger samples are
      required to confirm these findings.

PMID- 24898131
TI  - Single nucleotide polymorphism and haplotype effects associated with somatic cell
      score in German Holstein cattle.
AB  - BACKGROUND: To better understand the genetic determination of udder health, we
      performed a genome-wide association study (GWAS) on a population of 2354 German
      Holstein bulls for which daughter yield deviations (DYD) for somatic cell score
      (SCS) were available. For this study, we used genetic information of 44 576
      informative single nucleotide polymorphisms (SNPs) and 11 725 inferred haplotype
      blocks. RESULTS: When accounting for the sub-structure of the analyzed
      population, 16 SNPs and 10 haplotypes in six genomic regions were significant at
      the Bonferroni threshold of P <= 1.14 * 10-6. The size of the identified regions
      ranged from 0.05 to 5.62 Mb. Genomic regions on chromosomes 5, 6, 18 and 19
      coincided with known QTL affecting SCS, while additional genomic regions were
      found on chromosomes 13 and X. Of particular interest is the region on chromosome
      6 between 85 and 88 Mb, where QTL for mastitis traits and significant SNPs for
      SCS in different Holstein populations coincide with our results. In all
      identified regions, except for the region on chromosome X, significant SNPs were
      present in significant haplotypes. The minor alleles of identified SNPs on
      chromosomes 18 and 19, and the major alleles of SNPs on chromosomes 6 and X were
      favorable for a lower SCS. Differences in somatic cell count (SCC) between
      alternative SNP alleles reached 14 000 cells/mL. CONCLUSIONS: The results support
      the polygenic nature of the genetic determination of SCS, confirm the importance
      of previously reported QTL, and provide evidence for the segregation of
      additional QTL for SCS in Holstein cattle. The small size of the regions
      identified here will facilitate the search for causal genetic variations that
      affect gene functions.

PMID- 24898134
TI  - Elevated mean platelet volume is associated with gestational diabetes mellitus.
AB  - The mean platelet volume (MPV) is an indicator of the average size and activity
      of platelets. Elevated MPV values are associated with larger and more active
      platelets and perceived as a new independent cardiovascular risk factor. The aim
      of this study was to determine the MPV in women with gestational diabetes
      mellitus (GDM) and to determine the correlation of MPV with metabolic parameters
      in GDM. We retrospectively analyzed 30 women with GDM and 38 body mass index
      matched women with healthy pregnancies as controls. MPV and platelet counts were
      recorded in the third trimester and at postpartum 6-12 months for GDM group and
      in the third trimester for control group. Third-trimester MPV was significantly
      higher in GDM group compared to control group (8.8 +/- 1.0 versus 8.1 +/- 0.7 fl,
      p = 0.002). In women with GDM, there was a significant decrease in MPV in the
      postpartum period (8.8 +/- 1.0 versus 8.1 +/- 0.8 fl, p < 0.001). Fasting plasma
      glucose levels and glucose area under the curve were positively correlated with
      third trimester MPV (r = 0.346, p = 0.007 and r = 0.346, p = 0.02, respectively).
      Our results indicate that MPV is increased in GDM. Monitoring MPV, which is
      widely available in clinical practice, may potentially identify women who will
      develop gestational diabetes during pregnancy.

PMID- 24898133
TI  - Regular menstrual cycles do not rule out ovarian damage in adult women with
      systemic lupus erythematosus.
AB  - The aim of this study was to evaluate ovarian reserve markers in women with
      systemic lupus erythematosus (SLE) and regular menstrual cycles, and explore the
      relationship of such markers with clinical and treatment features. This was a
      case-control study including 27 women with SLE and 27 controls. All participants
      were aged 18-40 years, were eumenorrheic and had not used hormone therapy or
      hormone contraceptives in the past six months. Clinical manifestations of SLE,
      past and current use of immunosuppressive therapy and organ damage index were
      assessed at a regular follow-up visit, while antral follicle count (AFC), serum
      anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH) were assessed
      at early follicular phase of menstrual cycle. AFC was significantly reduced in
      SLE women [median (interquartile interval) 7 (5-11) versus 11 (7-12), p = 0.029].
      AMH levels were more heterogeneous in SLE patients compared to the control group
      [1.23 (0.24-4.63) ng/ml versus 1.52 (1.33-1.88) ng/ml]. The SLE and control
      groups had similar serum FSH levels [6.44 (4.19-7.69) versus 7.5 (6.03-8.09)
      IU/L, p = 0.135]. AFC was inversely correlated with organ damage index (p =
      0.046) and cumulative dose of cyclophosphamide (p = 0.028), while AMH levels were
      negatively correlated with the maximal dose of corticosteroid ever used (p =
      0.003). These findings suggest that ovarian reserve may be decreased in women
      with SLE despite regular menstrual cycles.

PMID- 24898135
TI  - Metabolic disorder and obesity in 5027 Brazilian postmenopausal women.
AB  - OBJECTIVES: To evaluate the frequency of obesity in postmenopausal women and
      assess the potential effects of increased body mass index (BMI) on lipoprotein
      profile and on risk factors for arterial hypertension and diabetes. DESIGN: A
      cross-sectional study was conducted with 5027 postmenopausal Brazilian women.
      Analyses were performed of BMI and cardiovascular factors (systemic blood
      pressure [BP], total cholesterol, low-density lipoprotein, high-density
      lipoprotein [HDL-C], triglyceride, and fast glucose). The statistical analysis
      included the chi-square and Mann-Whitney tests. The significance level was set at
      5%. RESULTS: Obesity (BMI >30) in our study characterized approximately 30% of
      the 5027 postmenopausal women. The comparison of patients with normal BMI and
      those with high BMI showed that high BMI had a significant negative effect on BP,
      as evidenced by the increased frequency of hypertension in overweight and obese
      patients (>25) (p < 0.001), that it also negatively and significantly affected
      triglyceride (p < 0.001) and fast glucose levels (p < 0.001), and that it was
      linked significantly to low levels of HDL-C. CONCLUSION: Our data showed the high
      frequency of obesity in our population and of the cardiovascular risks (glucose,
      systemic arterial hypertension, and low HDL-C) associated with high BMI.

PMID- 24898137
TI  - Visual impairment and depression among socially vulnerable older adults in
      Armenia.
AB  - OBJECTIVES: Visual impairment in older adults is a major public health problem.
      Untreated visual impairment might negatively impact physical and psychological
      health. This study assessed the association between visual impairment and
      depression among socially vulnerable older adults (those aged 50 and above) in
      Armenia. METHOD: The survey and eye screenings were carried out among 339
      participants who were the residents of retirement homes and single older adults
      in the households. The study team used Golovin-Sivtsev chart and cycloplegic
      skiascopy to measure visual impairment and Center for Epidemiologic Studies
      Depression scale to measure depression. RESULTS: The prevalence of visual
      impairment in the sample was 13.3%. Almost 24.0% of participants reported
      depression symptoms. Participants living in the retirement homes had
      substantially higher rates of visual impairment (21.5%) and depression (28.0%)
      than those living in households (9.3% and 15.0%, respectively). The odds of
      having depression were higher among those with visual impairment compared to
      those without after adjusting for confounders (OR = 2.75; 95% CI: 1.29-5.87).
      Having at least one non-communicable disease was associated with depression (OR =
      2.47; 95% CI: 1.28-4.75). Living in the retirement home was marginally
      significantly associated with having depression. Other confounders included age,
      gender, education, physical activity, and smoking. CONCLUSION: Visual impairment
      was significantly associated with depression in socially vulnerable older adults
      in Armenia. Timely eye screenings in similar population groups could lead to
      early detection of visual impairment and prevention of visual loss and associated
      mental health problems.

PMID- 24898136
TI  - Cerebrovascular responses to submaximal exercise in women with COPD.
AB  - BACKGROUND: COPD patients have decreased physical fitness, and have an increased
      risk of vascular disease. In the general population, fitness is positively
      associated with resting cerebral blood flow velocity, however, little is known
      about the cerebrovascular response during exercise particularly in COPD patients.
      We hypothesized that COPD patients would have lower cerebral blood flow during
      exercise secondary to decreased physical fitness and underlying vascular disease.
      METHODS: Cardiopulmonary exercise testing was conducted in 11 women with GOLD
      stage I-II COPD, and 11 healthy controls to assess fitness. Cerebro- and cardio
      vascular responses were compared between groups during two steady-state exercise
      tests (50% peak O2 consumption and 30 W). The main outcome variable was peak
      middle cerebral artery blood flow velocity (VP) during exercise using
      transcranial Doppler ultrasonography. RESULTS: Physical fitness was decreased in
      COPD patients. VP was comparable between COPD and controls (25 +/- 22% versus 15
      +/- 13%, respectively; P > 0.05) when exercising at the same relative intensity,
      despite patients having higher blood pressure and greater arterial desaturation.
      However, VP was elevated in COPD (31 +/- 26% versus 13 +/- 10%; P <= 0.05) when
      exercising at the same workload as controls. CONCLUSIONS: Our results are
      contradictory to our a-priori hypothesis, suggesting that during matched
      intensity exercise, cerebral blood flow velocity is similar between COPD and
      controls. However, exercise at a modestly greater workload imposes a large
      physical demand to COPD patients, resulting in increased CBF compared to
      controls. Normal activities of daily living may therefore impose a large
      cerebrovascular demand in COPD patients, consequently reducing their
      cerebrovascular reserve capacity.

PMID- 24898138
TI  - Nevus depigmentosus and nevus of Ito: pigmentary twin spotting.

PMID- 24898139
TI  - TAO1 kinase maintains chromosomal stability by facilitating proper congression of
      chromosomes.
AB  - Chromosomal instability can arise from defects in chromosome-microtubule
      attachment. Using a variety of drug treatments, we show that TAO1 kinase is
      required for ensuring the normal congression of chromosomes. Depletion of TAO1
      reduces the density of growing interphase and mitotic microtubules in human
      cells, showing TAO1's role in controlling microtubule dynamics. We demonstrate
      the aneugenic nature of chromosome-microtubule attachment defects in TAO1
      depleted cells using an error-correction assay. Our model further strengthens the
      emerging paradigm that microtubule regulatory pathways are important for
      resolving erroneous kinetochore-microtubule attachments and maintaining the
      integrity of the genome, regardless of the spindle checkpoint status. 

PMID- 24898140
TI  - Mutational analysis of dimeric linkers in peri- and cytoplasmic domains of
      histidine kinase DctB reveals their functional roles in signal transduction.
AB  - Membrane-associated histidine kinases (HKs) in two-component systems respond to
      environmental stimuli by autophosphorylation and phospho-transfer. HK typically
      contains a periplasmic sensor domain that regulates the cytoplasmic kinase domain
      through a conserved cytoplasmic linker. How signal is transduced from the ligand
      binding site across the membrane barrier remains unclear. Here, we analyse two
      linker regions of a typical HK, DctB. One region connects the first transmembrane
      helix with the periplasmic Per-ARNT-Sim domains, while the other one connects the
      second transmembrane helix with the cytoplasmic kinase domains. We identify a
      leucine residue in the first linker region to be essential for the signal
      transduction and for maintaining the delicate balance of the dimeric interface,
      which is key to its activities. We also show that the other linker, belonging to
      the S-helix coiled-coil family, plays essential roles in signal transduction
      inside the cell. Furthermore, by combining mutations with opposing activities in
      the two regions, we show that these two signalling transduction elements are
      integrated to produce a combined effect on the final activity of DctB. 

PMID- 24898141
TI  - Autophagy and apoptosis: parent-of-origin genome-dependent mechanisms of cellular
      self-destruction.
AB  - Functional genomic imprinting is necessary for the transfer of maternal resources
      to mammalian embryos. Imprint-free embryos are unable to establish a viable
      placental vascular network necessary for the transfer of resources such as
      nutrients and oxygen. How the parental origin of inherited genes influences
      cellular response to resource limitation is currently not well understood.
      Because such limitations are initially realized by the placenta, we studied how
      maternal and paternal genomes influence the cellular self-destruction responses
      of this organ specifically. Here, we show that cellular autophagy is prevalent in
      androgenetic (i.e. having only a paternal genome) placentae, while apoptosis is
      prevalent in parthenogenetic (i.e. having only a maternal genome) placentae. Our
      findings indicate that the parental origin of inherited genes determines the
      placenta's cellular death pathway: autophagy for androgenotes and apoptosis for
      parthenogenotes. The difference in time of arrest between androgenotes and
      parthenogenotes can be attributed, at least in part, to their placentae's
      selective use of these two cell death pathways. We anticipate our findings to be
      a starting point for general studies on the parent-of-origin regulation of
      autophagy. Furthermore, our work opens the door to new studies on the involvement
      of autophagy in pathologies of pregnancy in which the restricted transfer of
      maternal resources is diagnosed. 

PMID- 24898143
TI  - Hypothalamic neurogenesis is not required for the improved insulin sensitivity
      following exercise training.
AB  - Neurons within the hypothalamic arcuate nucleus (ARC) are important regulators of
      energy balance. Recent studies suggest that neurogenesis in the ARC is an
      important regulator of body mass in response to pharmacological stressors.
      Regular exercise training improves insulin action, and is a primary treatment
      modality for obesity and type 2 diabetes. We examined whether exercise training
      causes hypothalamic neurogenesis and whether this contributes to exercise-induced
      improvements in insulin action. Short-term exercise in adult mice induced a
      proneurogenic transcriptional program involving growth factors, cell
      proliferation, and neurogenic regulators in the hypothalamus. Daily exercise
      training for 7 days increased hypothalamic cell proliferation 3.5-fold above that
      of sedentary mice, and exercise-induced cell proliferation was maintained in diet
      induced obese mice. Colocalization studies indicated negligible neurogenesis in
      the ARC of sedentary or exercise-trained mice. Blocking cell proliferation via
      administration of the mitotic blocker arabinosylcytosine (AraC) did not affect
      food intake or body mass in obese mice. While 4 weeks of exercise training
      improved whole-body insulin sensitivity compared with sedentary mice, insulin
      action was not affected by AraC administration. These data suggest that regular
      exercise training induces significant non-neuronal cell proliferation in the
      hypothalamus of obese mice, but this proliferation is not required for enhanced
      insulin action. 

PMID- 24898142
TI  - Fat mass and obesity-associated gene (FTO) is linked to higher plasma levels of
      the hunger hormone ghrelin and lower serum levels of the satiety hormone leptin
      in older adults.
AB  - The mechanisms through which common polymorphisms in the fat mass and obesity
      associated gene (FTO) drive the development of obesity in humans are poorly
      understood. Using cross-sectional data from 985 older people (50% females) who
      participated at age 70 years in the Prospective Investigation of the Vasculature
      in Uppsala Seniors (PIVUS), circulating levels of ghrelin and leptin were
      measured after an overnight fast. In addition, subjects were genotyped for FTO
      rs17817449 (AA, n = 345 [35%]; AC/CA, n = 481 [48.8%]; CC, n = 159 [16.1%]).
      Linear regression analyses controlling for sex, self-reported physical activity
      level, fasting plasma glucose, and BMI were used. A positive relationship between
      the number of FTO C risk alleles and plasma ghrelin levels was found (P = 0.005;
      relative plasma ghrelin difference between CC and AA carriers = ~ 9%). In
      contrast, serum levels of the satiety-enhancing hormone leptin were inversely
      linked to the number of FTO C risk alleles (P = 0.001; relative serum leptin
      difference between CC and AA carriers = ~ 11%). These associations were also
      found when controlling for waist circumference. The present findings suggest that
      FTO may facilitate weight gain in humans by shifting the endocrine balance from
      the satiety hormone leptin toward the hunger-promoting hormone ghrelin.

PMID- 24898144
TI  - Effect of guanylate cyclase-C activity on energy and glucose homeostasis.
AB  - Uroguanylin is a gastrointestinal hormone primarily involved in fluid and
      electrolyte handling. It has recently been reported that prouroguanylin, secreted
      postprandially, is converted to uroguanylin in the brain and activates the
      receptor guanylate cyclase-C (GC-C) to reduce food intake and prevent obesity. We
      tested central nervous system administration of two GC-C agonists and found no
      significant reduction of food intake. We also carefully phenotyped mice lacking
      the GC-C receptor and found them to have normal body weight, adiposity, and
      glucose tolerance. Interestingly, uroguanylin knockout mice had a small but
      significant increase in body weight and adiposity that was accompanied by glucose
      intolerance. Our data indicate that the modest effects of uroguanylin on energy
      and glucose homeostasis are not mediated by central GC-C receptors. 

PMID- 24898147
TI  - Preparation and photoelectrochemical behavior of 1,4,6,8,11,13-hexazapentacene
      (HAP).
AB  - Photoelectrochemical studies demonstrated that 1,4,6,8,11,13-hexazapentacene
      (HAP) exhibited active n-type semiconductor behavior under visible light (lambda
      > 400 nm) illumination.

PMID- 24898148
TI  - Synthesis of metal-organic-framework related core-shell heterostructures and
      their application to ion enrichment in aqueous conditions.
AB  - We show a step-by-step strategy to fabricate MOF related core-shell
      heterostructures and successfully obtain SiO2@HKUST-1 core-shell nanospheres,
      which display the distinct ion separation ability of valving the sorption
      desorption of fluoride ions by controlling the pH. 

PMID- 24898145
TI  - SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo.
AB  - Cyclic AMP promotes chronic expression of target genes mainly by protein kinase A
      dependent activation of CREB transcription factor machineries in the metabolic
      tissues. Here, we wanted to elaborate whether CREB-regulated transcription factor
      (CRTC)2 and its negative regulator salt-inducible kinase (SIK)2 are involved in
      the transcriptional control of the metabolic pathway in adipocytes. SIK2 knockout
      (SIK2 KO) mice exhibited higher blood glucose levels that were associated with
      impaired glucose and insulin tolerance. Hypertriglyceridemia was apparent in SIK2
      KO mice, mainly due to the increased lipolysis from white adipocytes and the
      decreased fatty acid uptake in the peripheral tissues. Investigation of white
      adipocytes revealed the increases in fat cell size and macrophage infiltration,
      which could be linked to the metabolic anomaly that is associated in these mice.
      Interestingly, SIK2 KO promoted the enhancement in the CRTC2-CREB transcriptional
      pathway in white adipocytes. SIK2 KO mice displayed increased expression of
      activating transcription factor (ATF)3 and subsequent downregulation of GLUT4
      expression and reduction in high-molecular weight adiponectin levels in the
      plasma, leading to the reduced glucose uptake in the muscle and white adipocytes.
      The effect of SIK2-dependent regulation of adipocyte metabolism was further
      confirmed by in vitro cell cultures of 3T3 L1 adipocytes and the differentiated
      preadipocytes from the SIK2 or CRTC2 KO mice. Collectively, these data suggest
      that SIK2 is critical in regulating whole-body glucose metabolism primarily by
      controlling the CRTC2-CREB function of the white adipocytes. 

PMID- 24898149
TI  - Decreased tumour necrosis factor-alpha production by monocytes of granulomatosis
      with polyangiitis.
AB  - OBJECTIVES: We hypothesized that monocytes in patients with granulomatosis with
      polyangiitis (GPA) are polarized towards alternative activation with decreased
      tumour necrosis factor (TNF)-alpha production and that tissue-infiltrating
      monocytes/macrophages in granulomatous GPA lesions express CD163, a marker of
      alternative macrophage activation. METHOD: CD16+ monocytes in peripheral blood
      mononuclear cells (PBMCs) were quantified by flow cytometry. Monocytes were
      stimulated with increasing concentrations of lipopolysaccharide (LPS), and TNF
      alpha production was measured at 4 and 24 h. CD163 expression in lung biopsies of
      patients with GPA was detected by immunohistochemistry. RESULTS: Circulating
      CD16+ monocytes were more frequent in GPA patients compared to controls (4.7 +/-
      2.8% vs. 1.9 +/- 1.2%, p < 0.001). Upon activation with LPS, TNF-alpha production
      did not differ between CD16+ and CD16- monocytes. Stimulated monocytes from GPA
      patients produced significantly less TNF-alpha compared with monocytes from
      healthy controls (2903 +/- 1320 pg/mL vs. 8335 +/- 4569 pg/mL, p < 0.001).
      Macrophages expressing CD163 were enriched in granulomatous lung lesions of GPA
      patients. CONCLUSIONS: Decreased TNF-alpha production by circulating monocytes
      and CD163 overexpression by tissue monocytes/macrophages in granulomatous
      pulmonary lesions may suggest that monocytes/macrophages are alternatively
      activated in GPA.

PMID- 24898146
TI  - Trends in incidence of type 1 diabetes among non-Hispanic white youth in the
      U.S., 2002-2009.
AB  - The SEARCH for Diabetes in Youth Study prospectively identified youth aged <20
      years with physician-diagnosed diabetes. Annual type 1 diabetes (T1D) incidence
      per 100,000 person-years (95% CI) overall, by age-group, and by sex were
      calculated for at-risk non-Hispanic white (NHW) youth from 2002 through 2009.
      Joinpoint and Poisson regression models were used to test for temporal trends.
      The age- and sex-adjusted incidence of T1D increased from 24.4/100,000 (95% CI
      23.9-24.8) in 2002 to 27.4/100,000 (26.9-27.9) in 2009 (P for trend = 0.0008).
      The relative annual increase in T1D incidence was 2.72% (1.18-4.28) per year;
      2.84% (1.12-4.58) per year for males and 2.57% (0.68-4.51) per year for females.
      After adjustment for sex, significant increases were found for youth aged 5-9
      years (P = 0.0023), 10-14 years (P = 0.0008), and 15-19 years (P = 0.004) but not
      among 0-4-year-olds (P = 0.1862). Mean age at diagnosis did not change. The
      SEARCH study demonstrated a significant increase in the incidence of T1D among
      NHW youth from 2002 through 2009 overall and in all but the youngest age-group.
      Continued surveillance of T1D in U.S. youth to identify future trends in T1D
      incidence and to plan for health care delivery is warranted. 

PMID- 24898151
TI  - 130- versus 135-degree sliding hip screws and failure in pertrochanteric hip
      fractures.
AB  - BACKGROUND: The fixed-angle sliding hip screw has become a popular method of
      fixation for pertrochanteric hip fractures. The tip-to-apex distance (TAD)
      concept was introduced by Baumgaertner et al. in 1995 and has subsequently become
      a decisive predictor of the successfulness of fixation. The 135-degree plate has
      become the most popular plate used for fracture fixation, although this has not
      been compared with lower angled plates (130 degree) in relation to TAD. METHOD:
      We analysed 567 consecutive cases of dynamic hip screw (DePuy-Synthes) fixation
      to compare TAD in various angled plates and rate of failure. RESULTS: The 130
      degree plate has significantly lower mean TAD 19.3 mm versus 20.8 mm (P = 0.016).
      There were nine failures because of superior screw cut-out in the 135-degree
      plates and 0 failures in the 130-degree plates. CONCLUSION: We believe the
      improved trajectory for lag screw placement using 130-degree angled plates leads
      to a lower TAD and improved fixation in pertrochanteric fractures.

PMID- 24898150
TI  - Discovery of hapten-specific scFv from a phage display library and applications
      for HER2-positive tumor imaging.
AB  - In this study, an anti-hapten antibody (single chain Fv, scFv) against a hapten
      probe was developed as a unique reporter system for molecular imaging or therapy.
      The hapten peptide (histamine-succinyl-GSYK, Him) was synthesized for phage
      displayed scFv affinity selection and for conjugation with cypate (Cy-Him) for in
      vivo near-infrared (NIR) optical imaging. Hapten-specific scFvs were affinity
      selected from the human single fold phage display scFv libraries (Tomlinson I +
      J) with high specificity and affinity. Utilizing HER2 targeting as a model
      system, the highest affinity scFv (clone J42) was recombinantly fused to an anti
      HER2 affibody (scFv-L-Aff) with no loss of affinity of either protein. The
      functionality of the hapten-scFv reporter system was tested in vitro with a HER2
      positive human breast cancer cell line, SK-BR3, and in vivo with SK-BR3
      xenografts. ScFv-L-Aff mediated the binding of the hapten to HER2 on SK-BR3 cells
      and from tissue from the SK-BR3 xenograft; however, scFv-L-Aff did not mediate
      uptake of the hapten in the SK-BR3 xenografted tumors, presumably due to rapid
      internalization of the HER2/scFv-L-Aff complex. Our results suggest that this
      hapten-peptide and anti-hapten scFv can be a universal reporter system in a wide
      range of imaging and therapeutic applications. 

PMID- 24898152
TI  - Positive parenting.
AB  - AIM: While parenting has been researched and explored in both the professional
      and public realms, elements of the current key constructs involving the positive
      parenting of a child are still missing. The aim of this article is to define the
      concept of positive or "good" parenting to further extend research toward child
      health promotion knowledge across disciplines. METHODS: The Walker and Avant's
      concept analysis method was applied to this analysis. SOURCES: Published
      literature and Google search on the worldwide web. CONCLUSION: This analysis
      provides a definition of positive parenting. The key constructs found within this
      definition build a foundation for further research to develop measurable outcomes
      for positive parenting skills. These variables can also assist with research aims
      geared toward interventions to promote positive parenting.

PMID- 24898153
TI  - Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic
      ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders
      affecting women of reproductive age. It is characterized by chronic anovulation,
      hyperandrogenism, and insulin resistance. It is the main cause of infertility due
      to the menstrual dysfunction and metabolic disorders. Women with PCOS also have
      an increased cardiovascular risk because of dyslipidemia and insulin resistance.
      So far, we have a lot of information about the etiology of PCOS, and many steps
      forward have been made about the diagnosis of this syndrome, but there is still
      no certainty about the therapy. Myo-inositol (MI) and D-chiro-inositol, two
      inositol stereoisomers, have been proven to be effective in PCOS treatment.
      However, only MI has been shown to have beneficial effects on reproductive
      function, whereas the administration of MI/D-chiro-inositol, in the physiological
      plasma ratio (i.e., 40:1) ensures better clinical results, such as the reduction
      of insulin resistance, androgens' blood levels, cardiovascular risk and
      regularization of menstrual cycle with spontaneous ovulation. 

PMID- 24898154
TI  - Centrifugation versus PureGraft for fatgrafting to the breast after breast
      conserving therapy.
AB  - BACKGROUND: Breast-conserving treatment (BCT) leads to a progressive and
      deteriorating breast deformity. Fatgrafting is ideal for breast reconstruction
      after BCT. The most frequently utilized technique for fat processing is
      centrifugation. The PureGraft device (Cytori Therapeutics, San Diego, CA, USA) is
      a new method that involves washing and filtering the fat to prepare the graft. We
      compared the subjective and objective outcomes of two fat-processing methods,
      centrifugation and PureGraft filtration. METHODS: Thirty patients underwent
      breast reconstruction performed by a single surgeon (OM) after BCT in our
      department between April 2011 and September 2012. The patients were
      preoperatively divided into two groups randomly: 15 received fatgrafts processed
      by centrifugation, and 15 received fatgrafts processed by washing in PureGraft
      bags. The patients were followed up for 12 to 30 months. To measure the
      subjective outcome, we distributed the BREAST-Q questionnaire to all the patients
      both preoperatively and 1 year postoperatively. The BCCT.core software evaluated
      the objective outcome of breast reconstruction by fatgrafting. RESULTS: The
      Breast-Q results indicated a tremendous improvement in the modules "Satisfaction
      with Breast" and "Psychosocial Well-being". The "Sexual Well-being" scale also
      improved. Only the module "Satisfaction with Breasts" significantly differed
      between groups; patients treated with the PureGraft fat exhibited better
      outcomes. The BCCT.core results did not significantly differ between the groups.
      CONCLUSION: One year postoperatively, the outcomes of the use of PureGraft bags
      or centrifugation to process fat for breast reconstruction after BCT did not
      differ. The unpredictability of the results following fatgrafting procedures is
      likely due to interindividual differences with yet-undisclosed causes.

PMID- 24898157
TI  - Chronic wound care: a systematized review of Internet resources available to
      patients.

PMID- 24898156
TI  - The role of bile acids in functional GI disorders.
AB  - BACKGROUND: Bile acids are increasingly implicated in the pathogenesis of
      functional GI disorders. New mechanisms have recently been described in the
      irritable bowel syndrome, chronic diarrhea and chronic idiopathic constipation.
      Identification of bile acid signaling through farnesoid X receptor (FXR),
      transmembrane G-coupled receptor 5 (TGR5) and fibroblast growth factor 19 (FGF19)
      has led to the development of new, directly acting therapeutic agents. Despite
      these advances primary bile acid diarrhea remains under-recognized partly because
      of the lack of a widely available diagnostic test. PURPOSE: In this review we
      will summarize the effects of bile acids on bowel function throughout the
      gastrointestinal tract and their roles in the pathogenesis of functional
      diseases. We will review established diagnostic tests and therapies for
      functional heartburn, dyspepsia and bile acid diarrhea. There will be a
      particular emphasis on recent trial data for emerging therapies such as
      Elobixibat and Obeticholic acid and novel diagnostic tests for bile acid diarrhea
      such as 7alpha-Hydroxy-4-cholesten-3-one (C4) and FGF19. Finally we will discuss
      future directions for research in this rapidly evolving field, such as bacterial
      bile acid modification and identification of genetic anomalies associated with
      functional disorders.

PMID- 24898158
TI  - Preparation and characterisation of high-density ionic liquids incorporating
      halobismuthate anions.
AB  - A range of ionic liquids containing dialkylimidazolium cations and halobismuthate
      anions ([BiBr(x)Cl(y)I(z)](-) and [Bi2Br(x)Cl(y)I(z)](-)) were synthesised by
      combining dialkylimidazolium halide ionic liquids with bismuth(III) halide salts.
      The majority were room temperature liquids, all with very high densities. The
      neat ionic liquids and their mixtures with 1-butyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide were characterised using Densitometry,
      Viscometry, NMR Spectroscopy, Electrospray Ionisation Mass Spectrometry (ESI),
      Liquid Secondary Ion Mass Spectrometry (LSIMS), Matrix-assisted Laser
      Desorption/Ionization Mass Spectrometry (MALDI), X-Ray Photoelectron Spectroscopy
      (XPS) and Thermogravimetric Analysis (TGA), to establish their speciation and
      suitability for high-temperature applications.

PMID- 24898155
TI  - Greater monoamine oxidase a binding in perimenopausal age as measured with carbon
      11-labeled harmine positron emission tomography.
AB  - IMPORTANCE: Perimenopause is a period of high risk for mood disorders, and it has
      been proposed that perimenopause is also a window of risk for processes linked to
      later dementia. However, in human perimenopause, the neurobiological changes
      implicated in the genesis of mood disorders or dementia have not been identified.
      Monoamine oxidase A (MAO-A) is an important brain enzyme that creates oxidative
      stress, influences apoptosis, and metabolizes monoamines. After declines in
      estrogen level, MAO-A density may be elevated for a month or longer, and repeated
      declines in estrogen level occur with greater magnitude during perimenopause.
      OBJECTIVE: To investigate whether MAO-A total distribution volume (VT), an index
      of MAO-A density, is elevated in women of perimenopausal age (41-51 years).
      DESIGN, SETTING, AND PARTICIPANTS: In a cross-sectional study at a tertiary care
      psychiatric hospital, 58 women underwent carbon 11-labeled harmine positron
      emission tomography. These included 19 young women of reproductive age (mean
      [SD], 28.26 [5.05] years), 27 women of perimenopausal age (mean [SD] age, 45.21
      [3.41] years; including 14 women with change in menstrual cycle length with a
      mean [SD] age of 45.50 [4.00] years and 13 women with no change in menstrual
      cycle length with a mean [SD] age of 44.92 [2.81] years), and 12 women in
      menopause (mean [SD] age, 56.25 [3.19] years). MAIN OUTCOMES AND MEASURES: Values
      of MAO-A VT in the prefrontal cortex, anterior cingulate cortex, dorsal striatum,
      ventral striatum, thalamus, hippocampus, and midbrain. RESULTS: On average, MAO-A
      VT in perimenopausal age was elevated by 34% compared with reproductive age and
      by 16% compared with menopause (multivariate analysis of variance, group effect,
      F16,94 = 3.03; P < .001). Within the perimenopausal age group, meeting Stages of
      Reproductive Aging Workshop criteria for perimenopause, which is mainly based on
      menstrual cycle length, was not associated with MAO-A VT (F8,18 = 0.548; P = .81)
      but tendency to cry was positively correlated with MAO-A VT in the prefrontal
      cortex (r = 0.54; P = .008). CONCLUSIONS AND RELEVANCE: To our knowledge, this is
      the first report of a change in a central biomarker during perimenopausal age
      that is also present during major depressive episodes and high-risk states for
      major depressive episodes. The functions of MAO-A influence oxidative stress and
      apoptosis, 2 processes implicated as excessive in both mood disorders and
      dementia. Hence, greater MAO-A VT during perimenopause may represent a new target
      for assessing novel interventions to prevent mood disorders and reduce longer
      term risk of neurodegenerative disease.

PMID- 24898159
TI  - Fibroblast growth factor receptor (FGFR) gene amplifications are rare events in
      bladder cancer.
AB  - AIMS: Activating point mutations and protein overexpression of fibroblast growth
      factor receptors (FGFRs), especially FGFR3, are frequent events in bladder
      cancer. Little is known about gene amplifications, therefore we characterized
      amplification of FGFR1-3 by fluorescence in-situ hybridization (FISH). METHODS
      AND RESULTS: Tumours of 153 patients (n = 65 pTa low-grade, n = 15 pTa high
      grade, n = 37 pT1, n = 20 pT2, n = 10 pT3, n = 6 pT4) were analysed by FISH for
      FGFR1-3 copy numbers and screened for FGFR3 mutations and immunohistochemical
      protein expression. Amplifications of FGFR1 were found in 1.6% (two of 122),
      FGFR2 in 0.8% (one of 121) and FGFR3 in 3.4% (five of 145). All amplifications
      were high-level amplifications, not overlapping with polysomy. Amplifications
      were found in papillary/papillary-invasive tumour parts, and predominantly in
      tumours with enhanced Ki67 index (>10%), aberrant CK20 expression, and low p53
      expression. All FGFR3-amplified samples showed concomitant FGFR3 mutations and
      FGFR3 protein overexpression. FGFR amplifications were not associated
      significantly with gender, age, grade or stage in statistical analyses.
      CONCLUSIONS: FGFR amplifications are rare events in bladder cancer, with FGFR3
      amplification being the most prevalent (3.4% of cases). Concomitant FGFR3
      mutations and protein overexpression indicate that FGFR3-mediated signalling in
      these tumours would probably be highly active. This patient subgroup may be
      particularly suited to FGFR-targeted pharmacotherapy.

PMID- 24898160
TI  - A patient-centered network approach to multidisciplinary-guideline development: a
      process evaluation.
AB  - BACKGROUND: Guideline development and uptake are still suboptimal; they focus on
      clinical aspects of diseases rather than on improving the integration of care. We
      used a patient-centered network approach to develop five harmonized guidelines
      (one multidisciplinary and four monodisciplinary) around clinical pathways in
      fertility care. We assessed the feasibility of this approach with a detailed
      process evaluation of the guideline development, professionals' experiences, and
      time invested. METHODS: The network structure comprised the centrally located
      patients and the steering committee; a multidisciplinary guideline development
      group (gynecologists, physicians, urologists, clinical embryologists, clinical
      chemists, a medical psychologist, an occupational physician, and two patient
      representatives); and four monodisciplinary guideline development groups. The
      guideline development addressed patient-centered, organizational, and medical
      technical key questions derived from interviews with patients and professionals.
      These questions were elaborated and distributed among the groups. We evaluated
      the project performance, participants' perceptions of the approach, and the time
      needed, including time for analysis of secondary sources, interviews with eight
      key figures, and a written questionnaire survey among 35 participants. RESULTS:
      Within 20 months, this approach helped us develop a multidisciplinary guideline
      for treating infertility and four related monodisciplinary guidelines for general
      infertility, unexplained infertility, male infertility, and semen analysis. The
      multidisciplinary guideline included recommendations for the main medical
      technical matters and for organizational and patient-centered issues in clinical
      care pathways. The project was carried out as planned except for minor
      modifications and three extra consensus meetings. The participants were
      enthusiastic about the approach, the respect for autonomy, the project
      coordinator's role, and patient involvement. Suggestions for improvement included
      timely communication about guideline formats, the timeline, participants'
      responsibilities, and employing a librarian and more support staff. The 35
      participants spent 4497 hours in total on this project. CONCLUSIONS: The novel
      patient-centered network approach is feasible for simultaneously and
      collaboratively developing a harmonized set of multidisciplinary and
      monodisciplinary guidelines around clinical care pathways for patients with
      fertility problems. Further research is needed to compare the efficacy of this
      approach with more traditional approaches.

PMID- 24898161
TI  - Primary systemic (amyloid light-chain) amyloidosis masquerading as pseudoxanthoma
      elasticum: recognizing a novel clinicopathological pattern.
AB  - IMPORTANCE: Primary systemic (amyloid light-chain [AL]) amyloidosis has a variety
      of cutaneous manifestations. In this case, we present a novel clinicopathological
      pattern of AL amyloidosis. OBSERVATIONS: A woman in her 50s with a history of AL
      amyloidosis manifesting as macroglossia and bilateral carpal tunnel syndrome
      presented with skin-colored to yellow cobblestoned plaques to the neck and
      bilateral antecubital fossa. Although clinical similar to pseudoxanthoma
      elasticum (PXE), the skin changes were found to be due to amyloid deposition
      primarily around the pilosebaceous unit but also within the papillary and
      reticular dermis. Previous reports of PXE-like plaques in AL amyloidosis have
      been reported as part of a very rare entity termed amyloid elastosis. However,
      our case demonstrates several important clinical and pathological differences
      from this entity. Most notably, there was no dermal elastic fiber involvement,
      limited cutaneous and systemic involvement, and a fairly indolent course with
      better response to treatment. CONCLUSIONS AND RELEVANCE: Identification of this
      atypical presentation of AL amyloidosis has important implications for early
      detection and rapid treatment. The lack of elastic fiber involvement establishes
      the uniqueness of this case, and further study may be required to determine if
      this histological finding has prognostic significance.

PMID- 24898163
TI  - T7 bacteriophage induced changes of gold nanoparticle morphology: biopolymer
      capped gold nanoparticles as versatile probes for sensitive plasmonic biosensors.
AB  - The morphological changes of gold nanoparticles induced by T7 virus
      (bacteriophage) and the determination of its femtomolar concentration by a
      plasmonic method are presented. Carboxymethyl chitosan capped gold nanoparticles
      (CMC-AuNPs) are used as plasmonic probes and are synthesized by a simple one pot
      wet chemical method. HR-TEM images show that the spherical structure of the CMC
      AuNPs is changed into chain-like nanostructures after the addition of T7 virus
      due to the strong coordination of CMC-AuNPs with T7. Since T7 capsids comprise a
      repeating motif of capsomers built from proteins that bind to the acid groups of
      chitosan, the conjugation of carboxymethyl chitosan-linked AuNPs with T7 virions
      enables colorimetric biosensing detection. The absorbance intensity (~610 nm)
      increases in the concentration range of T7 from 2 * 10(-15) M to 2 * 10(-13) M
      and the detection limit is found to be 2 * 10(-15) M (2 fM). The present work
      demonstrates eco-friendly biopolymer stabilized AuNPs as potential nanomaterials
      for biosensing of viruses. Our method is very simple, low cost, selective and
      highly sensitive, and provides new insight into virus induced chain-like
      morphology of AuNPs. 

PMID- 24898162
TI  - US-like strain of porcine epidemic diarrhea virus outbreaks in Taiwan, 2013-2014.
AB  - Since late 2013, several outbreaks of porcine epidemic diarrhea virus (PEDV)
      infection have emerged in Taiwan. Suckling piglets under 2 weeks of age showed
      severe vomiting and watery yellowish diarrhea with morbidity and mortality
      ranging from 80 to 100% and 90 to 100%, respectively. A total of 68 samples from
      25 pig farms were confirmed as positive for PEDV and negative for rotavirus and
      transmissible gastroenteritis virus by reverse transcription PCR, and the partial
      S gene of PEDV was analyzed. Phylogenetic analysis places all 18 Taiwanese PEDV
      isolates collected during this outbreak in the same clade as the US strains of
      PEDV. This novel PEDV is prevailing and currently causing severe outbreaks in
      Taiwan. 

PMID- 24898164
TI  - Smokeless tobacco use among working adults - United States, 2005 and 2010.
AB  - Smokeless tobacco causes cancers of the oral cavity, esophagus, and pancreas. CDC
      analyzed National Health Interview Survey (NHIS) data to estimate the proportion
      of U.S. working adults who used smokeless tobacco in 2005 and 2010, by industry
      and occupation. This report describes the results of that analysis, which showed
      no statistically significant change in the prevalence of smokeless tobacco use
      among workers from 2005 (2.7%) to 2010 (3.0%). In 2010, smokeless tobacco use was
      highest among adults aged 25-44 years (3.9%), males (5.6%), non-Hispanic whites
      (4.0%), those with no more than a high school education (3.9%), and those living
      in the South (3.9%). By industry, the prevalence of smokeless tobacco use ranged
      from 1.5% in education services to 18.8% in mining industries, and by occupation
      from 1.3% in office and administrative support to 10.8% in construction and
      extraction. These findings highlight opportunities for reducing the health and
      economic burdens of tobacco use among U.S. workers, especially those in certain
      industries (e.g., mining) and occupations (e.g., construction and extraction)
      where use of smokeless tobacco is especially common. CDC recommends best
      practices for comprehensive tobacco control programs, including effective
      employer interventions, such as providing employee health insurance coverage for
      proven cessation treatments, offering easily accessible help for those who want
      to quit, and establishing and enforcing tobacco-free workplace policies. 

PMID- 24898165
TI  - Influenza activity - United States, 2013-14 season and composition of the 2014-15
      influenza vaccines.
AB  - During the 2013-14 influenza season in the United States, influenza activity
      increased through November and December before peaking in late December.
      Influenza A (H1N1)pdm09 (pH1N1) viruses predominated overall, but influenza B
      viruses and, to a lesser extent, influenza A (H3N2) viruses also were reported in
      the United States. This influenza season was the first since the 2009 pH1N1
      pandemic in which pH1N1 viruses predominated and was characterized overall by
      lower levels of outpatient illness and mortality than influenza A (H3N2)
      predominant seasons, but higher rates of hospitalization among adults aged 50-64
      years compared with recent years. This report summarizes influenza activity in
      the United States for the 2013-14 influenza season (September 29, 2013-May 17,
      2014?) and reports recommendations for the components of the 2014-15 Northern
      Hemisphere influenza vaccines. 

PMID- 24898166
TI  - Vital signs: foodborne norovirus outbreaks - United States, 2009-2012.
AB  - INTRODUCTION: Norovirus is the leading cause of acute gastroenteritis and
      foodborne disease in the United States, causing an estimated one in 15 U.S.
      residents to become ill each year as well as 56,000-71,000 hospitalizations and
      570-800 deaths, predominantly among young children and the elderly. Whereas
      noroviruses often spread through person-to-person contact, foodborne transmission
      can cause widespread exposures and presents important prevention opportunities.
      METHODS: CDC analyzed 2009-2012 data on suspected and confirmed norovirus
      outbreaks reported by state, local, and territorial health departments through
      the National Outbreak Reporting System (NORS) to characterize the epidemiology of
      foodborne norovirus outbreaks. RESULTS: During 2009-2012, a total of 1,008
      foodborne norovirus outbreaks were reported to NORS, constituting 48% of all
      foodborne outbreaks with a single known cause. Outbreaks were reported by 43
      states and occurred year round. Restaurants were the most common setting (64%) of
      food preparation reported in outbreaks. Of 520 outbreaks with factors
      contributing to contamination reported, food workers were implicated as the
      source in 70%. Of 324 outbreaks with an implicated food, most resulted from food
      contaminated during preparation (92%) and food consumed raw (75%). Specific food
      categories were implicated in only 67 outbreaks; the most frequently named were
      vegetable row crops (e.g., leafy vegetables) (30%), fruits (21%), and mollusks
      (19%). CONCLUSIONS: Noroviruses are the leading cause of reported foodborne
      disease outbreaks and most often associated with contamination of food in
      restaurants during preparation by infected food workers. IMPLICATIONS FOR PUBLIC
      HEALTH PRACTICE: Improved adherence to appropriate hand hygiene, excluding ill
      staff members from working until >=48 hours after symptom resolution, and
      supervision by certified kitchen managers are all recommended to reduce the
      incidence of foodborne norovirus disease.

PMID- 24898167
TI  - Measles - United States, January 1-May 23, 2014.
AB  - Measles is a highly contagious, acute viral illness that can lead to serious
      complications and death. Although measles elimination (i.e., interruption of year
      round endemic transmission) was declared in the United States in 2000,
      importations of measles cases from endemic areas of the world continue to occur,
      leading to secondary measles cases and outbreaks in the United States, primarily
      among unvaccinated persons. To update national measles data in the United States,
      CDC evaluated cases reported by states from January 1 through May 23, 2014. A
      total of 288 confirmed measles cases have been reported to CDC, surpassing the
      highest reported yearly total of measles cases since elimination (220 cases
      reported in 2011). Fifteen outbreaks accounted for 79% of cases reported,
      including the largest outbreak reported in the United States since elimination
      (138 cases and ongoing). The large number of cases this year emphasizes the need
      for health-care providers to have a heightened awareness of the potential for
      measles in their communities and the importance of vaccination to prevent
      measles. 

PMID- 24898168
TI  - Notes from the field: chikungunya virus spreads in the Americas - Caribbean and
      South America, 2013-2014.
AB  - In December 2013, the World Health Organization reported the first local
      transmission of chikungunya virus in the Western Hemisphere, with autochthonous
      cases identified in Saint Martin. Since then, local transmission has been
      identified in 17 countries or territories in the Caribbean or South America
      (Anguilla, Antigua and Barbuda, British Virgin Islands, Dominica, Dominican
      Republic, French Guiana, Guadeloupe, Guyana, Haiti, Martinique, Puerto Rico,
      Saint Barthelemy, Saint Kitts and Nevis, Saint Lucia, Saint Martin, Saint Vincent
      and the Grenadines, and Sint Maarten). As of May 30, 2014, a total of 103,018
      suspected and 4,406 laboratory-confirmed chikungunya cases had been reported from
      these areas. The number of reported cases nearly doubled during the previous 2
      weeks. More than 95% of the cases have been reported from five jurisdictions:
      Dominican Republic (38,656 cases), Martinique (30,715), Guadeloupe (24,428),
      Haiti (6,318), and Saint Martin (4,113). The highest incidences have been
      reported from Saint Martin (115 cases per 1,000 population), Martinique (76 per
      1,000), Saint Barthelemy (74 per 1,000), and Guadeloupe (52 per 1,000). Further
      expansion of these outbreaks and spread to other countries in the region is
      likely. 

PMID- 24898169
TI  - Detecting well casing leaks in Bangladesh using a salt spiking method.
AB  - We apply fluid-replacement logging in arsenic-contaminated regions of Bangladesh
      using a low-cost, down-well fluid conductivity logging tool to detect leaks in
      the cased section of wells. The fluid-conductivity tool is designed for the
      developing world: it is lightweight and easily transportable, operable by one
      person, and can be built for minimal cost. The fluid-replacement test identifies
      leaking casing by comparison of fluid conductivity logs collected before and
      after spiking the wellbore with a sodium chloride tracer. Here, we present
      results of fluid-replacement logging tests from both leaking and non-leaking
      casing from wells in Araihazar and Munshiganj, Bangladesh, and demonstrate that
      the low-cost tool produces measurements comparable to those obtained with a
      standard geophysical logging tool. Finally, we suggest well testing procedures
      and approaches for preventing casing leaks in Bangladesh and other developing
      countries. 

PMID- 24898170
TI  - Outcomes of tracheostomy following congenital heart surgery: a contemporary
      experience.
AB  - INTRODUCTION: Following congenital heart surgery, pediatric patients may
      experience persistent respiratory failure that requires tracheostomy placement.
      Currently, definitive knowledge of the optimal timing for tracheostomy placement
      in this patient population is lacking. METHODS: An 8-year retrospective review of
      17 pediatric patients who underwent congenital heart surgery and subsequently
      required tracheostomy placement was performed. Patients were evaluated with
      regard to the timing of tracheostomy and mortality. RESULTS: The overall study
      mortality was 24%. The median duration of intubation prior to tracheostomy was 60
      days (interquartile range: 19-90 days); there was no difference in the average
      time between intubation and tracheostomy for survivors compared with nonsurvivors
      (51 vs. 73 days, P = .37). No difference was observed in the overall duration of
      positive pressure ventilation when tracheostomy was performed within 30 days of
      intubation compared with greater than 30 days following intubation (481 vs. 451
      days, P = .88). Overall, 18% of patients were successfully weaned from the
      ventilator after a median duration of positive pressure ventilation of 212 days.
      CONCLUSION: The timing of tracheostomy placement may be an important factor in
      clinical outcomes for pediatric patients with persistent dependence on mechanical
      ventilatory support following congenital heart surgery. A larger, multi
      institution study may help further elucidate our observed clinical findings in
      this patient population.

PMID- 24898171
TI  - HOXB13 regulates the prostate-derived Ets factor: implications for prostate
      cancer cell invasion.
AB  - HOXB13 has been shown to enhance the invasive potential of breast and endometrial
      tumors. HOXB13 is also abundant in castration-resistant prostate tumors. To
      determine the invasive potential of HOXB13 in prostate tumors, highly metastatic
      PC3 prostate cancer cells were manipulated to express HOXB13 and/or the prostate
      derived Ets factor (PDEF). The PDEF is believed to reduce the invasive potential
      of various tumors, including prostate tumors. To further demonstrate the
      functional correlation between HOXB13 and PDEF, transwell invasion and gelatin
      zymography assays were performed. In addition, the western blot analysis was used
      to demonstrate the expression of PDEF target proteins involved in cancer cell
      migration and invasion, MMP-9 and survivin. According to the results, HOXB13
      promoted PC3 cell migration and invasion. The DNA microarray analysis
      demonstrated that HOXB13 significantly suppressed the expression of the PDEF.
      Accordingly, the expression of MMP-9 and survivin was regulated by HOXB13. In
      addition, HOXB13 promoted the invasive potential of PC3 cells while inhibiting
      the PDEF. The coexpression of HOXB13 and the PDEF led to moderate retardation of
      the number of invasive cells, indicating that HOXB13 functionally counteracted
      cell invasion by reducing PDEF expression. The western blot analysis demonstrated
      that HOXB13 counteracted the PDEF-mediated inhibition of the expression of PDEF
      target proteins such as MMP-9 and survivin. The results suggest that the HOXB13
      mediated promotion of tumor cell invasion is accomplished mainly through the
      downregulation of PDEF expression. 

PMID- 24898172
TI  - Design amphiphilic dipolar pi-systems for stimuli-responsive luminescent
      materials using metastable states.
AB  - pi-Conjugated compounds that exhibit tunable luminescence in the solid state
      under external mechanical stimuli have potential applications in sensors and
      imaging devices. However, no rational designs have been proposed that impart
      these mechano-responsive luminescent properties to pi-conjugated compounds. Here
      we demonstrate a strategy for mechano-responsive luminescent materials by
      imparting amphiphilic and dipolar characteristics to a luminescent pi-conjugated
      system. The oligo(p-phenylenevinylene) luminophore with a didodecylamino group at
      one end and a tri(ethylene glycol) ester group at the other end yields segregated
      solid structures by separately aggregating its hydrophobic and hydrophilic
      moieties. The segregated structures force the molecules to align in the same
      direction, thereby generating a conflict between the side-chain aggregation and
      dipolar stabilization of the pi-system. Consequently, these metastable solid
      structures can be transformed through mechanical stimulation to a more stable
      structure, from a pi-pi stacked aggregate to a liquid crystal and further to a
      crystalline phase with variable luminescence. 

PMID- 24898173
TI  - The impact of conditional cash transfers on child health in low- and middle
      income countries: a systematic review.
AB  - OBJECTIVES: The review aimed to assess the effectiveness of conditional cash
      transfers (CCTs) in improving child health in low- and middle-income countries.
      METHODS: Seven electronic databases were searched for papers: MEDLINE, EMBASE,
      PubMed, PsychINFO, BIOSIS Previews, Academic Search Complete, and CSA
      Sociological Abstracts. The included studies comprised of randomised controlled
      trials and controlled before-and-after studies evaluating the impact of CCTs on
      child health. Due to the substantial heterogeneity of the studies, a narrative
      synthesis was conducted on the extracted data. RESULTS: Sixteen studies
      predominantly from Latin American countries met the inclusion criteria. The
      outcomes reported by the studies in relation to CCTs' effectiveness in improving
      child health were reduction in morbidity risk, improvement in nutritional
      outcomes, health services utilisation, and immunisation coverage. CONCLUSIONS:
      The review suggests that to a large extent, CCTs are effective in improving child
      health by addressing child health determinants such as access to health care,
      child and maternal nutrition, morbidity risk, immunisation coverage, and
      household poverty in developing countries particularly middle-income countries.
      Of importance to both policy and practice, it appears that CCTs require effective
      functioning of health care systems to effectively promote child health.

PMID- 24898174
TI  - Killer behavior within the Candida parapsilosis complex.
AB  - A group of 29 isolates of Candida parapsilosis sensu stricto, 29 of Candida
      orthopsilosis, and 4 of Candida metapsilosis were assayed for the presence of
      killer activity using Saccharomyces cerevisiae ATCC 26609 as a sensitive strain.
      All C. metapsilosis isolates showed killer activity at 25  degrees C while
      strains of C. parapsilosis sensu stricto or C. orthopsilosis did not exhibit this
      activity. Sensitivity to killer toxins was evaluated using a set of previously
      reported killer strains of clinical origin. Only 11 isolates of the C.
      parapsilosis complex were inhibited by at least one killer isolate without
      resulting in any clear pattern, except for C. parapsilosis sensu stricto ATCC
      22019, which was inhibited by every killer strain with the exception of C.
      parapsilosis and Candida utilis. The lack of sensitivity to killer activity among
      isolates of the genus Candida suggests that their toxins belong to the same
      killer type. Differentiation of species within the C. parapsilosis complex using
      the killer system may be feasible if a more taxonomically diverse panel of killer
      strains is employed. 

PMID- 24898175
TI  - Associations of objectively assessed physical activity and sedentary time with
      health-related quality of life among colon cancer survivors.
AB  - BACKGROUND: The primary purpose of this study was to determine associations of
      accelerometer-assessed moderate- to vigorous-intensity physical activity (MVPA)
      and sedentary time with health-related quality of life (HRQoL) and physical
      function and well-being in colon cancer survivors. METHODS: Colon cancer
      survivors (N = 178) from Alberta, Canada (n = 92) and Western Australia (n = 86)
      completed a mailed survey that assessed HRQoL (Functional Assessment of Cancer
      Therapy-Colorectal), physical function and well-being (Trial Outcome Index
      Colorectal), and relevant covariates. MVPA and sedentary time were assessed using
      the Actigraph GT3X+ accelerometer (60-second epochs) via a 7-day monitoring
      protocol. Average daily MVPA and sedentary time was corrected for wear time and
      then examined as quartiles. RESULTS: Adjusting for relevant demographic,
      behavioral, and clinical covariates, a significant difference in HRQoL scores
      emerged between quartile 1 (Q1) and Q4 (M(diff) = 11.5, P = .038). For physical
      function and well-being, a significant difference emerged between Q1 and Q4
      (M(diff) = 9.1, P = .009). For fatigue, a significant difference emerged between
      Q1 and Q4 (M(diff) = 7.1, P = .05). Significant differences were also observed
      for between Q1 and Q3 (M(diff) = 2.4, P = .041), and Q1 and Q4 (M(diff) = 3.5, P
      = .002) for colorectal cancer-specific symptoms. There were no statistically
      significant associations of sedentary time with HRQoL, physical function and well
      being, fatigue, or colorectal cancer-specific symptoms. CONCLUSIONS: Objectively
      measured MVPA, but not sedentary time, was associated with better HRQoL, physical
      function and well-being, and colorectal cancer-specific symptoms in colon cancer
      survivors. For MVPA, differences met or exceeded contemporary cutpoints for
      determining clinically important differences.

PMID- 24898176
TI  - Effects of bisphenol A and fadrozole exposures on cyp19a1 expression in the
      Murray rainbowfish, Melanotaenia fluviatilis.
AB  - Several endocrine-disrupting chemicals (EDCs) have been attributed to the
      alteration of reproduction in fish through disrupting endogenous sex
      steroidogenic pathways including aromatisation of androgens to oestrogen by CYP19
      aromatase. Here we investigate this hypothesis in adult male and female
      Melanotaenia fluviatilis by examining the mRNA expression of cyp19a1 isoforms
      after exposure for <=96 h to two EDCs with contrasting modes of action: one a
      weak oestrogen mimic, bisphenol A [BPA (100 or 500 MUg/L)], and the other a
      nonsteroidal aromatase inhibitor, fadrozole [FAD (10 or 50 ug/L)]. The results
      suggest that BPA did not affect cyp19a1a expression significantly at both
      concentrations, whereas 50 ug/L of FAD significantly upregulated its expression
      in ovary. In contrast, BPA exposures increased expression of cyp19a1b in brain of
      both males and females, whilst FAD had contrasting effects in brain: It increased
      in males but decreased in females. Similar contrasting responses of cyp19a1b were
      induced by BPA in gonads: upregulation in ovary and downregulation in testis. FAD
      did not have a significant effect on gonadal expression of cyp19a1b.
      Collectively, the results suggest that BPA and FAD can disrupt cyp19a1b activity
      more readily than can cyp19a1a, albeit with contrasting effects in either a
      tissue- or sex-specific context that is conceivably consistent with their (BPA
      and FAD) opposing modes of action. Enhanced spatial and temporal sensitivity of
      cyp19a1b compared with cyp19a1a suggests that brain sex of fish is more
      susceptible to disruption by environmental pollutants such as BPA and FAD.
      Therefore, we propose that the response of cyp19a1b in brain tissue of M.
      fluviatilis is a more suitable indicator of oestrogenic pollution in the aquatic
      environment.

PMID- 24898177
TI  - Separation and purification of bioactive botrallin and TMC-264 by a combination
      of HSCCC and semi-preparative HPLC from endophytic fungus Hyalodendriella sp.
      Ponipodef12.
AB  - Two dibenzo-alpha-pyrones, botrallin (1) and TMC-264 (2) were preparatively
      separated from crude ethyl acetate extract of the endophytic fungus
      Hyalodendriella sp. Ponipodef12, which was isolated from the hybrid 'Neva' of
      Populus deltoides Marsh * P. nigra L. using a combination of high-speed counter
      current chromatography (HSCCC) and semi-preparative HPLC. Botrallin (1) with
      74.73% of purity and TMC-264 (2) with 82.29% of purity were obtained through
      HSCCC by employing a solvent system containing n-hexane-ethyl acetate-methanol
      water at a volume ratio of 1.2:1.0:0.9:1.0. It was the first time for TMC-264 (2)
      to be isolated from this fungus. TMC-264 (2) showed strong antimicrobial and
      antinematodal activity, and botrallin (1) exhibited moderate inhibitory activity
      on acetylcholinesterase.

PMID- 24898180
TI  - Multi-stimuli-responsive organometallic gels based on ferrocene-linked poly(aryl
      ether) dendrons: reversible redox switching and Pb2+-ion sensing.
AB  - We describe the design, synthesis, and "stimuli-responsive" study of ferrocene
      linked Frechet-type [poly(aryl ether)]-dendron-based organometallic gels, in
      which the ferrocene moiety is attached to the dendron framework through an acyl
      hydrazone linkage. The low-molecular-weight gelators (LMWGs) form robust gels in
      both polar and non-polar solvent/solvent mixtures. The organometallic gels
      undergo stimuli-responsive behavior through 1) thermal, 2) chemical, and 3)
      electrochemical methods. Among them, conditions 1 and 3 lead to seamlessly
      reversible with repeated cycles of identical efficiency. Results indicate that
      the flexible nature of the poly(aryl ether) dendron framework plays a key role in
      retaining the reversible electrochemical behavior of ferrocene moiety in the
      LMWGs. Further, the organometallic gelators have exhibited unique selectivity
      towards Pb(2+) ions (detection limit ~10(-8)  M). The metal ion-sensing results
      in a gel-sol phase transition associated with a color change visible to the naked
      eye. Most importantly, decomplexing the metal ion from the system leads to the
      regeneration of the initial gel morphology, indicating the restoring ability of
      the organometallic gel. The metal-ligand binding nature has been analyzed by
      using (1)H NMR spectroscopy, mass spectrometry, and DFT calculations.

PMID- 24898178
TI  - 16S rRNA gene phylogeny and tfdA gene analysis of 2,4-D-degrading bacteria
      isolated in China.
AB  - Twenty-two 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacterial isolates
      were collected from agricultural soils at three sites in China. Sequence analysis
      of the 16S rRNA genes indicated that the isolates were phylogenetically grouped
      into four categories: Ochrobactrum anthropi, in the Alpha- class of the phylum
      Proteobacteria (3 out of 22 isolates), Cupriavidus sp., of the Betaproteobacteria
      (3 out of 22), Pseudomonas sp. and Stenotrophomonas sp., which are
      Gammaproteobacteria (7 out of 22), and Bacillus sp., of the phylum Firmicutes (9
      out of 22). Primers were designed to amplify the conserved domain of tfdA, which
      is known to be involved in the degradation of 2,4-D. Results showed that the tfdA
      genes of all 22 strains were most similar to that of Cupriavidus necator JMP134,
      which belongs to the 2,4-D/alpha-ketoglutarate dioxygenase TfdA protein family,
      indicating that the JMP134-type tfdA gene is likely to be almost universal among
      the 2,4-D-degrading bacteria isolated from China. Degradation abilities of these
      22 strains were investigated in assays using 2,4-D as the sole source of carbon
      and energy. Thirteen strains degraded >60 % of the available 2,4-D (500 mg l(-1))
      over a 1-week incubation period, while a further nine Bacillus sp. strains
      degraded 50-81 % of the available 2,4-D. None of these nine strains degraded
      other selected herbicides, such as mecoprop, 2-methyl-4-chlorophenoxyacetic acid,
      quizalofop, and fluroxypyr. This is the first report of 2,4-D-degradation by
      Bacilli.

PMID- 24898179
TI  - Effect of earlier unfolded protein response and efficient protein disposal system
      on cellulase production in Rut C30.
AB  - Trichoderma reesei (T. reesei) has been widely used in production of cellulolytic
      enzymes and heterologous proteins because of its high secretion capacity. The
      lack of knowledge on protein secretion mechanisms, however, still hinders
      rational improvement on cellulase production. The transcript levels of cellulases
      and components involved in post-transcriptional procedures were compared in this
      study between two mutants, QM9414 and Rut C30 for evaluating the effects of
      modification and secretion upon cellulase production. The results showed that
      cellulase induction by cellulose drastically up-regulated expressions of the
      sensor of unfolded protein, chaperone and folding-assisted enzymes in endoplasmic
      reticulum and resulted in unfolded protein response (UPR) and low-grade increase
      in secretory transporters' expression similar to that of chemical treatment. Rut
      C30 demonstrated earlier and more sustainable expressions of elements involved in
      UPR and lower amount of cellular retained cellulase compared to QM9414,
      indicating that Rut C30 had hypercellulolytic property partially for its earlier
      and enhanced UPR to more efficiently dispose of protein. Modifying post
      translational peptides and enhancing protein flux to avoid protein accumulation
      during cellulase production may be a feasible approach for strain improvement.

PMID- 24898181
TI  - Simultaneous determination of cinnamaldehyde and its metabolite in rat tissues by
      gas chromatography-mass spectrometry.
AB  - Cinnamaldehyde (CA), an active ingredient isolated from the traditional Chinese
      medicine Cortex Cinnamomi, has a wide range of bioactivities. To clarify the
      distribution characteristics of CA, a selective and sensitive method utilizing
      gas chromatography-mass spetrometry was initially developed for simultaneously
      determining the concentration of CA and its metabolite cinnamyl alcohol in rat
      tissues. Selected ion masses of m/z 131, 105 and 92 were chosen, and separation
      of the analytes was performed on a DB-5 ms (30 m * 0.25 mm, 0.25 um, thickness)
      capillary column by gas chromatography-mass spectrometry. The calibration curves
      demonstrated good linearity and reproducibility over the range of 20-2000 and 20
      4000 ng/mL for various tissue samples. Recoveries ranged from 86.8 to 107.5%,
      while intra- and interday relative standard deviations were all <11.3%. The
      analysis method was successfully applied in tissue distribution studies for CA
      and cinnamyl alcohol. As CA and cinnamyl alcohol may inter-convert to one
      another, simultaneous determination of both analytes provides a comparative and
      accurate data for tissue study. The concentrations of CA and cinnamyl alcohol
      remaining in spleen were the highest among the main organs, including heart,
      liver, spleen, lung, kidney and brain. In addition, there was no long-term
      accumulation of CA in rat tissues.

PMID- 24898182
TI  - Molecular aspects of adipoepithelial transdifferentiation in mouse mammary gland.
AB  - The circular, reversible conversion of the mammary gland during pregnancy and
      involution is a paradigm of physiological tissue plasticity. The two most
      prominent cell types in mammary gland, adipocytes and epithelial cells, interact
      in an orchestrated way to coordinate this process. Previously, we showed that
      this conversion is at least partly achieved by reciprocal transdifferentiation
      between mammary adipocytes and lobulo-alveolar epithelial cells. Here, we aim to
      shed more light on the regulators of mammary transdifferentiation. Using
      immunohistochemistry with cell type-specific lipid droplet-coating markers
      (Perilipin1 and 2), we show that cells with an intermediate adipoepithelial
      phenotype exist during and after pregnancy. Nuclei of cells with similar
      transitional structural characteristics are highly positive for Elf5, a master
      regulator of alveologenesis. In cultured adipocytes, we could show that transient
      and stable ectopic expression of Elf5 induces expression of the milk component
      whey acidic protein, although the general adipocyte phenotype is not affected
      suggesting that additional pioneering factors are necessary. Furthermore, the
      lack of transdifferentiation of adipocytes during pregnancy after clearing of the
      epithelial compartment indicates that transdifferentiation signals must emanate
      from the epithelial part. To explore candidate genes potentially involved in the
      transdifferentiation process, we devised a high-throughput gene expression study
      to compare cleared mammary fat pads with developing, contralateral controls at
      several time points during pregnancy. Incorporation of bioinformatic predictions
      of secretory proteins provides new insights into possible paracrine signaling
      pathways and downstream transdifferentiation factors. We discuss a potential role
      for osteopontin (secreted phosphoprotein 1 [Spp1]) signaling through integrins to
      induce adipoepithelial transdifferentiation.

PMID- 24898183
TI  - Studies on drug metabolism by fungi colonizing decomposing human cadavers. Part
      II: biotransformation of five model drugs by fungi isolated from post-mortem
      material.
AB  - The present study investigated the in vitro metabolic capacity of 28 fungal
      strains isolated from post-mortem material towards five model drugs:
      amitriptyline, metoprolol, mirtazapine, promethazine, and zolpidem. Each fungal
      strain was incubated at 25  degrees C for up to 120 h with each of the five
      models drugs. Cunninghamella elegans was used as positive control. Aliquots of
      the incubation mixture were centrifuged and 50 MUL of the supernatants were
      diluted and directly analyzed by liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) with product ion scanning. The remaining mixture was analyzed by full
      scan gas chromatography-mass spectrometry (GC-MS) after liquid-liquid extraction
      and acetylation. The metabolic activity was evaluated through the total number of
      detected metabolites (NDM) produced in each model and fungal strains and the
      percentage of parent drug remaining (%RPD) after up to five days of incubation.
      All the tested fungal strains were capable of forming mammalian phase I
      metabolites. Fungi from the normal fungal flora of the human body such as Candida
      sp., Geotrichum candidum, and Trichosporon asahii) formed up to seven metabolites
      at %RPD values greater than 52% but no new fungal metabolites (NFM). In contrast,
      some airborne fungal strains like Bjerkandera adusta, Chaetomium sp, Coriolopsis
      sp., Fusarium solani and Mucor plumbeus showed NDM values exceeding those of the
      positive control, complete metabolism of the parent drug in some models and
      formation of NFM. NFM (numbers in brackets) were detected in four of the five
      model drugs: amitriptyline (18), metoprolol (4), mirtazapine (8), and zolpidem
      (2). The latter NFM are potential candidates for marker substances indicating
      post-mortem fungal metabolism.

PMID- 24898184
TI  - Multifocal electroretinogram responses in Nepalese diabetic patients without
      retinopathy.
AB  - PURPOSE: To determine neuroretinal function with multifocal electroretinogram
      (mfERG) in diabetic subjects without retinopathy. METHODS: Multifocal
      electroretinogram (mfERG) was performed in 18 eyes of 18 diabetic subjects
      without retinopathy and 17 eyes of 17 age and gender-matched healthy control
      participants. Among 18 diabetic subjects, two had type 1 and 16 had type 2
      diabetes. MfERG responses were averaged by the retinal areas of six concentric
      rings and four quadrants, and 103 retinal locations; N1-P1 amplitude and P1
      implicit time were analysed. RESULTS: Average mfERG N1-P1 amplitude (in
      nv/deg(2)) of 103 retinal locations was 56.3 +/- 17.2 (mean +/- SD) in type 1
      diabetic subjects, 47.2 +/- 9.3 in type 2 diabetic subjects and 71.5 +/- 12.7 in
      controls. Average P1-implicit time (in ms) was 43.0 +/- 1.3 in type 1 diabetic
      subjects, 43.9 +/- 2.3 in type 2 diabetic subjects and 41.9 +/- 2.1 in controls.
      There was significant reduction in average N1-P1 amplitude and delay in P1
      implicit time in type 2 diabetic subjects in comparison to controls. mfERG
      amplitude did not show any significant correlation with diabetes duration and
      blood sugar level. However, implicit time showed a positive correlation with
      diabetes duration in type 2 diabetic subjects with diabetes duration >=5 years.
      CONCLUSIONS: This is the first study in a Nepalese population with diabetes using
      multifocal electroretinography. We present novel findings that mfERG N1-P1
      amplitude is markedly reduced along with delay in P1-implicit time in type 2
      diabetic subjects without retinopathy. These findings indicate that there might
      be significant dysfunction of inner retina before the development of diabetic
      retinopathy in the study population, which have higher prevalence of diabetes
      than the global estimate and uncontrolled blood sugar level.

PMID- 24898185
TI  - Acute coronary syndrome antiplatelet alternatives in clopidogrel allergy.
AB  - No published information exists to support the safe use of ticagrelor in patients
      with a clopidogrel allergy. This study involved an institutional review board
      approved retrospective review of patients with a documented clopidogrel allergy
      who subsequently received ticagrelor between July 2011 and February 2014. We
      report the cases of two patients with a history of hypersensitivity to
      clopidogrel in whom ticagrelor was used successfully without documented incident.
      In addition, principles suggesting a lack of cross-sensitivity between ticagrelor
      and clopidogrel are reviewed. These cases combined with theoretical evidence
      support the use of ticagrelor in patients with hypersensitivity to clopidogrel. 

PMID- 24898186
TI  - Continuous transversus abdominis plane block catheter analgesia for postoperative
      pain control in renal transplant.
AB  - PURPOSE: Continuous transversus abdominis plane (TAP) block using a catheter has
      proven its usefulness in reducing opioid requirements and pain scores after lower
      abdominal surgery. However, there are no reports of its successful use after
      renal transplant. We tested the hypothesis that continuous TAP block would
      retrospectively reduce opioid requirement, nausea score and hospital stay after
      renal transplant surgery. METHODS: In a retrospective study, we reviewed the data
      from 63 adult renal transplant recipients-31 with patient-controlled TAP
      analgesia with standing orders for intravenous as well as oral opioids as needed
      and 32 with intravenous patient-controlled analgesia. The TAP catheter was
      inserted preoperatively using an ultrasound-guided technique. Infusion of
      ropivacaine 0.2 % at 8 ml basal, 12 ml bolus and a lockout interval of 60 min
      were maintained for 48 h postoperatively. The primary outcome was total morphine
      equivalent dose during the 48-h postoperative period. Secondary outcomes were
      pain and nausea scores for the 48-h postoperative period. RESULTS: The mean 48-h
      postoperative morphine-equivalent doses [95 % confidence interval] for patient
      controlled intravenous analgesia and TAP catheter were 197 [111, 349] and 50 [28,
      90], respectively, which were significantly different (P = 0.002). The mean 48-h
      average verbal response pain scores were 2.94 [2.39, 3.50] and 2.49 [1.93, 3.06],
      respectively, which were not significantly different (P = 0.26). The mean nausea
      scores were 0.66 [0.46, 0.87] and 0.60 [0.40, 0.81], respectively, which were not
      significantly different (P = 0.69). There was no difference regarding hospital
      stay. CONCLUSION: The use of continuous TAP analgesia for postoperative analgesia
      after renal transplant was effective in reducing the morphine-equivalent
      requirements.

PMID- 24898188
TI  - Biomimetic polymers responsive to a biological signaling molecule: nitric oxide
      triggered reversible self-assembly of single macromolecular chains into
      nanoparticles.
AB  - Novel nitric oxide (NO) responsive monomers (NAPMA and APUEMA) containing o
      phenylenediamine functional groups have been polymerized to form NO-responsive
      macromolecular chains as truly biomimetic polymers. Upon exposure to NO--a
      ubiquitous cellular signaling molecule--the NAPMA- and APUEMA-labeled
      thermoresponsive copolymers exhibited substantial changes in solubility, clearly
      characterized by tuneable LCST behavior, thereby inducing self-assembly into
      nanoparticulate structures. Moreover, the NO-triggered self-assembly process in
      combination with environmentally sensitive fluorescence dyes could be employed to
      detect and image endogenous NO.

PMID- 24898187
TI  - Current role of PCNL in pediatric urolithiasis.
AB  - The incidence of pediatric stone disease has been increasing. Though there are
      geographical variations, there remains a common theme in that this is a high-risk
      population with regard to stone formation and recurrence. Consequently, it is
      important to keep the number of procedures performed to a minimum and to save the
      developing kidney from the deleterious effects of intervention. Of the number of
      available treatment options, Percutaneous Nephrolithotomy (PCNL) offers a number
      of distinct advantages albeit with its own set of concerns. In the present
      article, the current literature on PCNL in pediatric urolithiasis was reviewed by
      a MEDLINE/PubMed search that was limited to literature in the English language,
      with emphasis on the current state of art in PCNL. Within the last few years,
      there have been improvements in radiological techniques, particularly computed
      tomography (CT), with dedicated reconstructions and development of scoring
      systems leading to better preoperative planning. Also, there has been
      miniaturization of instruments, particularly smaller nephroscopes, innovative
      sheaths and the potential to use lasers as well as smaller pneumatic and
      ultrasound probes. The combination of these has led to various modifications,
      such as miniperc, microperc and ultra-mini perc techniques. These modifications
      have been shown to be associated with a decrease in morbidity and high clearance
      rates. In this article, we analyze the current role of PCNL and its
      modifications, in terms of the indications, techniques, results, and
      complications in management of pediatric urolithiasis.

PMID- 24898189
TI  - Changes in dietary practices and social organization during the pivotal late iron
      age period in Norway (AD 550-1030): isotope analyses of Merovingian and Viking
      Age human remains.
AB  - Human remains representing 33 individuals buried along the coast in northern
      Norway were analyzed for diet composition using collagen stable carbon and
      nitrogen isotope analysis. Where possible, both teeth and bone were included to
      investigate whether there were dietary changes from childhood to adulthood. A
      general shift was documented from the Merovingian Age 550-800 AD to the Viking
      Age AD 800-1050 (VA), with a heavier reliance on marine diet in the VA. Dietary
      life history data show that 15 individuals changed their diets through life with
      11 of these having consumed more marine foods in the later years of life. In
      combination with (87) Sr/(86) Sr data, it is argued that at least six individuals
      possibly originated from inland areas and then moved to the coastal region where
      they were eventually interred. The trend is considered in relation to the
      increasing expansion of the marine fishing industry at this time, and it is
      suggested that results from isotope analyses reflect the expanding production and
      export of stockfish in this region.

PMID- 24898191
TI  - Generation of plasmonic Au nanostructures in the visible wavelength using two
      dimensional parallel dip-pen nanolithography.
AB  - The fabrication and characterization of over millimeter (mm)-scale Au plasmonic
      structures are reported. Fishnet structures of Au are fabricated by the "bottom
      up (direct deposition of alkanethiol)" and "top-down (wet-etching of Au)"
      combined approach using massively parallel dip-pen nanolithography (DPN). An
      array of two-dimensional (2D) parallel 55,000 pens was used for the DPN writing
      of 1-octadecanethiol (ODT) on an Au film in an area of 10 mm * 10 mm. The
      plasmonic resonance of the over millimeter-scale Au fishnet structures is shown
      at the visible region around 500 nm, which is measured by ellipsometrical
      experiments and theoretical finite-difference time-domain (FDTD) calculation. It
      was demonstrated that massive metal plasmonic structures can be conveniently
      obtained by using DPN, complementary with both e-beam lithography and nanoimprint
      lithography.

PMID- 24898190
TI  - Can the Greulich and Pyle method be used on French contemporary individuals?
AB  - Forensic age estimation of living individuals has become increasingly important
      in forensic practice with the constant increase of migration movements to
      developed countries. The method of Greulich and Pyle is one of the most
      frequently used methods for age determination. The aim of our study was to verify
      the reliability of this method on a French contemporary population. We
      retrospectively analyzed 190 frontal hand and wrist radiographs of living
      subjects aged between 10 and 19 years (100 males and 90 females) performed in the
      Radiology Department of the University Hospital of Tours. These radiographs were
      compared with the Greulich and Pyle atlas to determine the skeletal age (SA) and
      to compare it to the chronological age (CA). We calculated the coefficient of
      correlation and the coefficient of determination for each sex group. The SA of
      our subjects was also inserted in the graphs provided by Greulich and Pyle in
      their atlas. Intra- and inter-observer variabilities were good, demonstrating the
      reproducibility and repeatability of the method. The correlation coefficients
      were high (0.98 for males and 0.93 for females) and comparable with published
      data. The mean difference between CA and SA was -2.29 months for males and -6.44
      months for females, showing an overestimation of CA for both sexes. No
      statistical difference was found between CA and SA for both male and female
      samples. We concluded that the method of Greulich and Pyle can be used on a
      contemporary French population but not without caution because of a tendency for
      this method to overestimate age. A fully developed hand and wrist does not allow
      to state that the 18th year of life is completed beyond a reasonable doubt. We
      recommend using it in association with other methods.

PMID- 24898193
TI  - The current and future use of imaging in urological robotic surgery: a survey of
      the European Association of Robotic Urological Surgeons.
AB  - BACKGROUND: With the development of novel augmented reality operating platforms
      the way surgeons utilise imaging as a real-time adjunct to surgical technique is
      changing. METHODS: A questionnaire was distributed via the European Robotic
      Urological Society mailing list. The questionnaire had three themes: surgeon
      demographics, current use of imaging and potential uses of an augmented reality
      operating environment in robotic urological surgery. RESULTS: 117 of the 239
      respondents (48.9%) were independently practising robotic surgeons. 74% of
      surgeons reported having imaging available in theatre for prostatectomy 97% for
      robotic partial nephrectomy and 95% cystectomy. 87% felt there was a role for
      augmented reality as a navigation tool in robotic surgery. CONCLUSIONS: This
      survey has revealed the contemporary robotic surgeon to be comfortable in the use
      of imaging for intraoperative planning it also suggests that there is a desire
      for augmented reality platforms within the urological community.

PMID- 24898192
TI  - A prospective study on self-assessed mental well-being and work capacity as
      determinants of all-cause sickness absence.
AB  - PURPOSE: The aim of the present study was to estimate whether self-assessed
      mental well-being and work capacity determines future sickness absence (SA).
      METHODS: A questionnaire was sent to employed individuals (n = 6,140), aged 19-64
      years, who were registered as sick-listed with a new sick-leave spell in 2008.
      The response rate was 54 %. In this study we included individuals with a single
      sick-leave spell in 2008 (n = 2,502). The WHO (Ten) Well-Being Index and four
      dimensions of self-assessed work capacity (knowledge, mental, collaborative,
      physical) were used as determinants. Future sickness absence was identified
      through national register in 2009. Outcome was defined as no sickness benefit
      compensated days (no SBCD) and at least one sickness benefit compensated day
      (SBCD). Logistic regression analyses were used to estimate odds ratios (OR) with
      95 % confidence intervals (CI) for the likelihood of SBCD. RESULTS: In 2009, 28 %
      of the women and 22 % of the men had SBCD; the median was 59 and 66 benefit days,
      respectively. Individuals with low mental well-being had higher odds for SBCD
      with OR 1.29 (95 % CI 1.01-1.65) in the fully adjusted model. Participants
      reporting low work capacity in relation to knowledge (OR 1.55, 95 % CI 1.13
      2.13), collaborative (OR 1.36, 95 % CI 1.03-1.79) and physical (OR 1.50, 95 % CI
      1.22-1.86) demands at work had higher odds for SBCD after adjustments for all
      covariates; no relation was demonstrated with mental work capacity (OR 0.99, 95 %
      CI 0.76-1.27). CONCLUSION: Mental well-being and work capacity emerged as
      determinants of future SA. Screening in health care could facilitate early
      identification of persons in need of interventions to prevent future SA.

PMID- 24898194
TI  - Donor splice-site mutation in CUL4B is likely cause of X-linked intellectual
      disability.
AB  - X-linked intellectual disability is the most common form of cognitive disability
      in males. Syndromic intellectual disability encompasses cognitive deficits with
      other medical and behavioral manifestations. Recently, a large family with a
      novel form of syndromic X-linked intellectual disability was characterized. Eight
      of 24 members of the family are male and had cognitive dysfunction, short
      stature, aphasia, skeletal abnormalities, and minor anomalies. To identify the
      causative gene(s), we performed exome sequencing in three affected boys, both
      parents, and an unaffected sister. We identified a haplotype consisting of eight
      variants located in cis within the linkage region that segregated with affected
      members in the family. Of these variants, two were novel. The first was at the
      splice-donor site of intron 7 (c.974+1G>T) in the cullin-RING ubiquitin ligase
      (E3) gene, CUL4B. This variant is predicted to result in failure to splice and
      remove intron 7 from the primary transcript. The second variant mapped to the 3'
      UTR region of the KAISO gene (c.1127T>G). Sanger sequencing validated the
      variants in these relatives as well as in three affected males and five carriers.
      The KAISO gene variant was predicted to create a binding site for the microRNAs
      miR-4999 and miR-4774; however, luciferase expression assays failed to validate
      increased targeting of these miRNAs to the variant 3'-UTR. This SNP may affect 3'
      UTR structure leading to decreased mRNA stability. Our results suggest that the
      intellectual disability phenotype in this family is caused by aberrant splicing
      and removal of intron 7 from CUL4B gene primary transcript.

PMID- 24898195
TI  - [The Clavien-Dindo classification of complications used for radical
      prostatectomy].
AB  - The objective of the present study was to evaluate perioperative complications
      between retropubic, endoscopic and robot-assisted radical prostatectomy on basis
      of a prospective maintained database using the Clavien-Dindo classification of
      complications. According to our results, implementation of the radical robot
      assisted laparoscopic prostatectomy shows a trend to a decrease of minor
      complications compared to retropubic and endoscopic radical prostatectomy. Major
      complications are comparable between all three procedures.

PMID- 24898199
TI  - Multiple parenchymal leiomyomas of the breast in a Sudanese female.
AB  - Leiomyomas are benign smooth muscle neoplasm. They can occur in any organ, but
      the most common forms occur in the uterus, small bowel and the esophagus.
      Leiomyomas of breast are rare benign non epithelial tumor. Only 21 cases of
      solitary parenchymal leiomyoma of the breast have been reported. This is the
      first case of multiple breast leiomyomas being reported in the literature. Here
      we report a case of a 38-year-old woman who presented to us with a painless right
      sided breast swelling. Histopathology revealed a growth pattern of interlacing
      fascicles of smooth-muscle cells consistent with leiomyoma of breast. To the best
      of our knowledge, this is the first case of multiple intraparenchymal leiomyomas
      of the breast reported in the literature. 

PMID- 24898198
TI  - Usefulness of intracardiac echocardiography with a mechanical probe for catheter
      based interventions: a 10-year prospective registry.
AB  - BACKGROUND: The clinical outcome benefit of intracardiac echocardiography (ICE)
      with a mechanical probe during congenital heart disease interventions has not
      been fully investigated. We reported the long-term results of a prospective
      registry of interatrial shunt closure guided by mechanical ICE. METHODS: We
      enrolled 537 patients (mean age 48 +/- 19.0 years, 378 females) submitted to ICE
      aided procedures in a prospective registry over a 10-year period (September 2003
      September 2013). All patients underwent transesophageal echocardiography (TEE)
      before the planned procedure. We evaluated (1) structure identification
      capability, (2) fossa ovale and interatrial septum component measurement, (3)
      procedure monitoring capability, (4) procedural and fluoroscopy times, and
      radiograph dose, (5) probe-related complications. RESULTS: ICE was successfully
      performed and was able to correctly identify the structures previously assessed
      by TEE in all patients. In 24 patients (4.5%), ICE allowed better anatomy
      definition than TEE. In 35 other patients (6.5%), ICE identified structures not
      observed by TEE, which led to change indications to interventions or the
      operative technique to be used. In 131 patients (24.4%), ICE evaluation led to
      change the planned device to be implanted. There was only one probe-related
      complication (0.2%). CONCLUSIONS: Mechanical ICE may offer a valid alternative to
      conventional TEE in guiding congenital heart disease interventional procedures.

PMID- 24898200
TI  - Intra-operative ultrasound versus wire-guided localization in the surgical
      management of non-palpable breast cancer.
AB  - BACKGROUND: Non-palpable breast lesions require some method of localization when
      performing breast conserving surgery (BCS). Despite the advent of newer
      techniques, ultrasound (US) and wire-guided localization (WGL) remain the most
      popular approaches. OBJECTIVE: We aim to compare the positive margin rate of US
      versus WGL in the excision of breast lesions. METHODS: Data were collected from
      the Clinical Access Portal. All patients who underwent US or WGL BCS were
      identified and consecutive data collected. Positive margins were evaluated using
      histopathology reports. Baseline demographics and specimen size data were also
      collected. RESULTS: A total of 198 patients were included in total over a three
      year period. There was some evidence of an association of type of surgery with
      positive margin (OR=2.11, p=0.075) where a 2.11 fold increase in the odds of a
      positive margin was estimated for the US method relative to WGL, but this was not
      statistically significant at the 5% level. This effect decreased after adjusting
      for potential confounders (OR=1.81, p=0.34). CONCLUSIONS: This retrospective
      study of US versus WGL in BCS demonstrated no significant difference in the
      positive margin rate, although a trend was observed in favor of the WGL group. We
      have provided further evidence for the debate on the accuracy of US and WGL for
      non-palpable breast lesions. Available data remains sparse, and our results
      contradict the findings of other comparative studies.

PMID- 24898196
TI  - Pyoderma gangrenosum: pathogenetic oriented treatment approaches.
AB  - Pyoderma gangrenosum (PG) shows features of autoimmune and autoinflammatory
      disorders. Genetic defects which affect the inflammasome, and in particular the
      NLRP3 zone, can cause an abnormal secretion of interleukin 1 (IL-1). IL-1 may be
      involved in clinical manifestation of certain (genetic) forms of PG. IL-1
      receptor antagonists reduce the activity of IL-1alpha and IL-1beta. Mutations in
      the PSTPIP1 gene have been identified in patients with pyogenic arthritis,
      pyoderma gangrenosum and acne syndrome. In patients with a pyoderma gangrenosum,
      acne, and suppurative hidradenitis syndrome these mutations cannot be found and
      the effect of IL-1 inhibition is questionable. Another upcoming opportunity is
      targeted therapy by tumor necrosis factor-alfa inhibitors in steroid-resistant
      patients. This review has been focused on (1) the modern pathogenetic concepts,
      (2) the currently accepted criteria for differentiating the disease, (3) the
      target therapy and (4) valuable advice to the clinicians regarding a number of
      medicaments capable of aggravating or inducing the PG.

PMID- 24898201
TI  - Robotic thyroidectomy using bilateral axillo-breast approach: Comparison of
      surgical results with open conventional thyroidectomy.
AB  - BACKGROUND: The aim of the present study was to compare the surgical outcomes of
      robotic thyroidectomy using the bilateral axillo-breast approach (BABA) with open
      conventional thyroidectomy. METHODS: Database of patients who underwent
      thyroidectomy with cervical lymph node dissection after diagnosed as papillary
      thyroid carcinoma between July 2008 and February 2013 were examined.
      Clinicopathologic characteristics, surgical outcomes, and postoperative
      morbidities of robot group and open group were investigated. RESULTS: The
      dominant tumor size (P=0.974), body mass index (BMI) (P=0.426), and the mean
      number of metastatic lymph nodes in central compartment neck dissection (P=0.269)
      were comparable between the two groups. The mean number of retrieved central
      lymph nodes was higher in the open group than in the robot group (P=0.001).
      Postoperative complications were comparable: hypoparathyroidism in 2 weeks
      (P=0.296) and 3 months (P=0.446) after the surgery; vocal cord palsy in 2 weeks
      (P=0.363) and 3 months (P=0.312); hematoma (P=0.162); and wound infection
      (P=0.421). CONCLUSIONS: Robotic thyroidectomy using BABA may be a technically
      feasible and safe procedure comparable to conventional open surgery especially in
      node-negative patients.

PMID- 24898202
TI  - Sequential sampling and paradoxes of risky choice.
AB  - The common-ratio, common-consequence, reflection, and event-splitting effects are
      some of the best-known findings in decision-making research. They represent
      robust violations of expected utility theory, and together form a benchmark
      against which descriptive theories of risky choice are tested. These effects are
      not currently predicted by sequential sampling models of risky choice, such as
      decision field theory (Busemeyer & Townsend 1993). This paper, however, shows
      that a minor extension to decision field theory, which allows for stochastic
      error in event sampling, can provide a parsimonious, cognitively plausible
      explanation for these effects. Moreover, these effects are guaranteed to emerge
      for a large range of parameter values, including best-fit parameters obtained
      from preexisting choice data. 

PMID- 24898203
TI  - Phenotypic consequences of LYS4 gene disruption in Candida albicans.
AB  - A BLAST search of the Candida Genome Database with the Saccharomyces cerevisiae
      LYS4 sequence known to encode homoaconitase (HA) revealed ORFs 19.3846 and
      19.11327. Both alleles of the LYS4 gene were sequentially disrupted in Candida
      albicans BWP17 cells using PCR-based methodology. The null lys4Delta mutant
      exhibited lysine auxotrophy in minimal medium but was able to grow in the
      presence of l-Lys and alpha-aminoadipate, an intermediate of the alpha
      aminoadipate pathway, at millimolar concentrations. The presence of d-Lys and
      pipecolic acid did not trigger lys4Delta growth. The C. albicans lys4Delta mutant
      cells demonstrated diminished germination ability. However, their virulence in
      vivo in a murine model of disseminated neonatal candidiasis appeared identical to
      that of the wild-type strain. Moreover, there was no statistically significant
      difference in fungal burden of infected tissues between the strains.

PMID- 24898204
TI  - Familial Kaposi's Sarcoma in HHV8 infected subjects presenting the G-174C allele
      of the IL-6 promoter: a possible role for EBV?

PMID- 24898205
TI  - Otolaryngologist-performed head and neck ultrasound: outcomes and challenges in
      learning the technique.
AB  - OBJECTIVE: To assess the feasibility and accuracy of otolaryngologist-performed
      ultrasound in evaluating head and neck pathology. METHOD: An ENT trainee, who had
      undergone basic training in neck ultrasonography, performed this on patients
      referred with suspected neck pathology. The trainee recorded the presence and
      nature of any abnormality. Findings were compared with those from a repeated scan
      performed by an experienced head and neck radiologist. RESULTS: The study
      included 250 patients. The absence or presence of lesion as reported by the
      trainee correlated with the radiologist's findings in 207 cases (83 per cent).
      There were 144 true positives, 63 true negatives, 32 false negatives and 11 false
      positives, yielding a sensitivity of 82 per cent, specificity of 85 per cent and
      accuracy of 83 per cent. Of the 144 true positive lesions, 81 per cent were
      interpreted concordantly with the radiologist. CONCLUSION: Neck ultrasonography
      performed by an otolaryngologist is less accurate than that performed by an
      experienced radiologist, but is still a useful adjunct to clinical assessment,
      facilitating assessment in a 'one-stop' clinical setting.

PMID- 24898206
TI  - Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)
      infected cynomolgus macaques.
AB  - BACKGROUND: Prion diseases are fatal neurodegenerative disorders whose
      pathogenesis mechanisms are not fully understood. In this context, the analysis
      of gene expression alterations occurring in prion-infected animals represents a
      powerful tool that may contribute to unravel the molecular basis of prion
      diseases and therefore discover novel potential targets for diagnosis and
      therapeutics. Here we present the first large-scale transcriptional profiling of
      brains from BSE-infected cynomolgus macaques, which are an excellent model for
      human prion disorders. RESULTS: The study was conducted using the GeneChip(r)
      Rhesus Macaque Genome Array and revealed 300 transcripts with expression changes
      greater than twofold. Among these, the bioinformatics analysis identified 86
      genes with known functions, most of which are involved in cellular development,
      cell death and survival, lipid homeostasis, and acute phase response signaling.
      RT-qPCR was performed on selected gene transcripts in order to validate the
      differential expression in infected animals versus controls. The results obtained
      with the microarray technology were confirmed and a gene signature was
      identified. In brief, HBB and HBA2 were down-regulated in infected macaques,
      whereas TTR, APOC1 and SERPINA3 were up-regulated. CONCLUSIONS: Some genes
      involved in oxygen or lipid transport and in innate immunity were found to be
      dysregulated in prion infected macaques. These genes are known to be involved in
      other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.
      Our results may facilitate the identification of potential disease biomarkers for
      many neurodegenerative diseases.

PMID- 24898207
TI  - Structural variation and missense mutation in SBDS associated with Shwachman
      Diamond syndrome.
AB  - BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive
      ribosomopathy caused mainly by compound heterozygous mutations in SBDS.
      Structural variation (SV) involving the SBDS locus has been rarely reported in
      association with the disease. We aimed to determine whether an SV contributed to
      the pathogenesis of a case lacking biallelic SBDS point mutations. CASE
      PRESENTATION: Whole exome sequencing was performed in a patient with SDS lacking
      biallelic SBDS point mutations. Array comparative genomic hybridization and
      Southern blotting were used to seek SVs across the SBDS locus. Locus-specific
      polymerase chain reaction (PCR) encompassing flanking intronic sequence was also
      performed to investigate mutation within the locus. RNA expression and Western
      blotting were performed to analyze allele and protein expression. We found the
      child harbored a single missense mutation in SBDS (c.98A > C; p.K33T), inherited
      from the mother, and an SV in the SBDS locus, inherited from the father. The
      missense allele and SV segregated in accordance with Mendelian expectations for
      autosomal recessive SDS. Complementary DNA and western blotting analysis and
      locus specific PCR support the contention that the SV perturbed SBDS protein
      expression in the father and child. CONCLUSION: Our findings implicate genomic
      rearrangements in the pathogenesis of some cases of SDS and support patients
      lacking biallelic SBDS point mutations be tested for SV within the SBDS locus.

PMID- 24898209
TI  - Pediatric Outpatient Feeding Clinic: If You Build It, Who Will Come?
AB  - BACKGROUND: Feeding disorders occur commonly in the pediatric population and vary
      in severity from picky eating to extreme food selectivity. The fifth edition of
      the Diagnostic and Statistical Manual of Mental Disorders and the International
      Classification of Diseases, 10th Revision provide more inclusive diagnostic
      criteria for feeding disorders, but little is known about the actual referral
      population to an outpatient feeding clinic. In this investigation, the nutrition
      status, reason for referral, and related exploratory questions of outpatient
      referrals are detailed. MATERIALS AND METHODS: Children aged 1-18 years were
      eligible for enrollment. Survey data collected included demographics, prior
      diagnoses, parental/caretaker complaint, mealtime duration, referral source, and
      food repertoire. Exploratory questions examined the impact of the feeding
      disorder on immediate family. RESULTS: Ten percent of participants had a weight
      for-height z score or body mass index score of <=-2. The most common
      parental/caretaker chief complaint were poor nutrition, food refusals, and poor
      weight gain. The food repertoire included 15 or fewer items (7%), between 15 and
      25 items (18%), or greater than 25 items (75%). The most positive responses to
      exploratory questions were mealtime frustration, lack of understanding by other
      family members, lack of access to appropriate treatment in a timely fashion, and
      inability to meet the child's feeding needs. CONCLUSION: Most referred infants
      and children were not undernourished. Despite this finding, most
      parents/caretakers were concerned about inadequate nutrition status and poor
      weight gain. Feeding disorders have an adverse effect on immediately family
      members. Revised diagnostic criteria should facilitate better identification of
      the broad spectrum of feeding disorders.

PMID- 24898208
TI  - Utility of Electronic Medical Records to Assess the Relationship Between
      Parenteral Nutrition and Central Line-Associated Bloodstream Infections in Adult
      Hospitalized Patients.
AB  - BACKGROUND: Parenteral nutrition is associated with increased central line
      associated bloodstream infections (CLABSIs). Electronic databases are important
      for identifying independent risk factors for prevention strategies. Our aims were
      to evaluate the utility of using electronic data sources to identify risk factors
      for CLABSIs, including parenteral nutrition (PN), and to assess the association
      between CLABSI and PN administration. METHODS: Data were obtained for all
      discharges of adult patients in whom a central line was inserted between
      September 1, 2007, and December 31, 2008, in a large, academically affiliated
      hospital in New York City. CLABSI was defined electronically using a modified
      definition from the Centers for Disease Control and Prevention. A manual chart
      review was also undertaken to assess validity/reliability of the electronic
      database and gather additional information. Risk factors for CLABSI were examined
      using logistic regression. RESULTS: Among 4840 patients, there were 220 CLABSIs,
      an incidence of 5.4 CLABSIs per 1000 central line days. Risk factors included PN
      (odds ratio [OR], 4.33; 95% confidence interval [CI], 2.50-7.48), intensive care
      unit stay (OR, 2.26; 95% CI, 1.58-3.23), renal disease (OR, 2.79; 95% CI, 2.00
      3.88), and immunodeficiency (OR, 2.26; 95% CI, 1.70-3.00). Diabetes mellitus was
      associated with reduced CLABSI rates (OR, 0.63; 95% CI, 0.45-0.88). CONCLUSIONS:
      The utility of electronic medical records for determining risk factors is limited
      by such things as free-text data entry. Using a hybrid between fully electronic
      and manual chart review, reliable data were obtained. PN is associated with a
      high risk for CLABSI in a population highly selected for indications for PN.

PMID- 24898210
TI  - Impact of Preoperative Prealbumin on Outcomes After Cardiac Surgery.
AB  - BACKGROUND: Preoperative malnutrition is increasingly prevalent in patients
      undergoing cardiac surgery. Although prealbumin is a widely used indicator of
      nutrition status, its use in the preoperative assessment of patients undergoing
      cardiac surgery is not well defined. The purpose of this study is to determine
      the impact of preoperative prealbumin levels on outcomes after cardiac surgery.
      MATERIALS AND METHODS: Data were prospectively gathered from February 2013 to
      July 2013 on 69 patients undergoing cardiac surgery. Prealbumin levels were
      obtained within 24 hours of surgery. Patients were divided into 2 groups based on
      a prealbumin cutoff value of 20 mg/dL. RESULTS: Of the 69 patients, 32 (46.4%)
      had a preoperative prealbumin <= 20 mg/dL. There was no correlation between
      prealbumin levels and body mass index (r = -0.13, P = .28). Likewise, there was
      no correlation between preoperative albumin and prealbumin levels (r = 0.09, P =
      .44). Nine of 32 (28.1%) patients with low preoperative prealbumin levels had
      postoperative infections compared with 2 of 37 (5.4%) patients with high
      prealbumin levels (P = .010). Patients with low prealbumin levels also had
      increased risk of postoperative intubation for > 12 hours (P = .010).
      CONCLUSIONS: Patients undergoing cardiac surgery with preoperative prealbumin
      levels of <= 20 mg/dL have an increased risk for postoperative infections and the
      need for longer mechanical ventilation. If feasible, nutrition optimization of
      such patients may be considered prior to cardiac surgery.

PMID- 24898212
TI  - Assessment of the physicochemical stability of all-in-one parenteral emulsions
      for neonates according to USP specifications, Athanasiou et al.

PMID- 24898211
TI  - Increased Anti-Flagellin and Anti-Lipopolysaccharide Immunoglobulins in Pediatric
      Intestinal Failure: Associations With Fever and Central Line-Associated
      Bloodstream Infections.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) pose a
      significant challenge in the lives of patients with intestinal failure (IF). We
      hypothesized that plasma immunoglobulins against flagellin (FLiC) and
      lipopolysaccharide (LPS) would be able to differentiate CLABSIs from nonbacterial
      febrile episodes and that levels would increase with infection and decline
      following appropriate antibiotic treatment. MATERIALS AND METHODS: Patients with
      IF, due to short bowel syndrome, between the ages of 3 months and 4 years of age,
      were recruited at Cincinnati Children's Hospital Medical Center. Anti-FLiC and
      anti-LPS plasma antibody levels were measured in 13 children with IF at baseline,
      during febrile events, and also following treatment with antibiotics. These were
      also measured in 11 healthy children without IF who were recruited as controls.
      RESULTS: Plasma anti-FLiC IgA levels increased during febrile episodes in all
      patients with IF (baseline mean of 1.10 vs febrile episode mean of 1.32 optical
      density units, respectively; P = .046). Neither plasma anti-FLiC nor anti-LPS IgA
      or IgG levels distinguished CLABSI from nonbacterial febrile episodes compared
      with baseline levels. Compared with controls, patients with IF had significantly
      higher plasma levels of anti-FLiC and anti-LPS IgA at baseline. CONCLUSION:
      Plasma anti-FLiC IgA antibody levels rise during febrile episodes but do not
      differentiate between nonbacterial febrile illnesses and CLABSIs in pediatric IF.
      However, the upregulation of these antibodies in IF suggests the baseline
      systemic presence of Gram-negative bacterial products.

PMID- 24898213
TI  - Fabrication of single-crystalline microspheres with high sphericity from
      anisotropic materials.
AB  - Microspheres with high sphericity exhibit unique functionalities. In particular,
      their high symmetry makes them excellent omnidirectional optical resonators. As
      such perfect micrometre-sized spheres are known to be formed by surface tension,
      melt cooling is a popular method for fabricating microspheres. However, it is
      extremely difficult to produce crystalline microspheres using this method because
      their surfaces are normally faceted. Only microspheres of polymers, glass, or
      ceramics have been available, while single-crystalline microspheres, which should
      be useful in optical applications, have been awaiting successful production. Here
      we report the fabrication of single-crystalline semiconductor microspheres that
      have surfaces with atomic-level smoothness. These microspheres were formed by
      performing laser ablation in superfluid helium to create and moderately cool a
      melt of the anisotropic semiconductor material. This novel method provides
      cooling conditions that are exceptionally suited for the fabrication of single
      crystalline microspheres. This finding opens a pathway for studying the hidden
      mechanism of anisotropy-free crystal growth and its applications. 

PMID- 24898214
TI  - Estimates of missing heritability for complex traits in Brown Swiss cattle.
AB  - BACKGROUND: Genomic selection estimates genetic merit based on dense SNP (single
      nucleotide polymorphism) genotypes and phenotypes. This requires that SNPs
      explain a large fraction of the genetic variance. The objectives of this work
      were: (1) to estimate the fraction of genetic variance explained by dense genome
      wide markers using 54 K SNP chip genotyping, and (2) to evaluate the effect of
      alternative marker-based relationship matrices and corrections for the base
      population on the fraction of the genetic variance explained by markers. METHODS:
      Two alternative marker-based relationship matrices were estimated using 35 706
      SNPs on 1086 dairy bulls. Both pedigree- and marker-based relationship matrices
      were fitted simultaneously or separately in an animal model to estimate the
      fraction of variance not explained by the markers, i.e. the fraction explained by
      the pedigree. The phenotypes considered in the analysis were the deregressed
      estimated breeding values (dEBV) for milk, fat and protein yield and for somatic
      cell score (SCS). RESULTS: When dEBV were not sufficiently accurate (50 or 70%),
      the estimated fraction of the genetic variance explained by the markers was
      around 65% for yield traits and 45% for SCS. Scaling marker genotypes with locus
      specific frequencies of heterozygotes slightly increased the variance explained
      by markers, compared with scaling with the average frequency of heterozygotes
      across loci. The estimated fraction of the genetic variance explained by the
      markers using separately both relationships matrices followed the same trends but
      the results were underestimated. With less accurate dEBV estimates, the fraction
      of the genetic variance explained by markers was underestimated, which is
      probably an artifact due to the dEBV being estimated by a pedigree-based animal
      model. CONCLUSIONS: When using only highly accurate dEBV, the proportion of the
      genetic variance explained by the Illumina 54 K SNP chip was approximately 80%
      for Brown Swiss cattle. These results depend on the SNP chip used and the family
      structure of the population, i.e. more dense SNPs and closer family relationships
      are expected to result in a higher fraction of the variance explained by the
      SNPs.

PMID- 24898215
TI  - Inter-professional agreement of ultrasound-based diagnoses in patients with
      shoulder pain between physical therapists and radiologists in the Netherlands.
AB  - STUDY DESIGN: Reliability study. OBJECTIVES: The aim of this study was to
      evaluate the interrater-reliability of the interpretation of diagnostic
      ultrasound in patients with shoulder pain between physical therapists and
      radiologists. BACKGROUND: Although physical therapists in The Netherlands
      increasingly use diagnostic ultrasound in clinical practice, there is no evidence
      available on its reliability. METHODS: A cohort study included patients with
      shoulder pain from primary care physiotherapy. Patients followed the usual
      diagnostic pathway of which diagnostic ultrasound could be a part. Patients that
      received diagnostic ultrasound also visited a radiologist within one week for a
      second one. Patients and radiologists were blinded for the diagnostic ultrasound
      diagnosis of the physical therapists. Agreement was assessed using Cohen's kappa
      statistics. Subgroup analysis was performed on education and experience. RESULTS:
      A total of 65 patients were enrolled and 13 physical therapists and 9
      radiologists performed diagnostic ultrasound. We found substantial agreement
      (0.63 K) between physical therapists and radiologists on the assessment of full
      thickness tears. The overall kappa of all four diagnostic categories was 0.36,
      indicating fair agreement. The more experienced and highly trained physical
      therapists showed moderate agreement (0.43 K) compared to only slight agreement
      (0.17 and 0.09 K) from the less experienced and trained physical therapists with
      radiologists. CONCLUSION: The reliability between physical therapists and
      radiologist on diagnostic ultrasound of shoulder patients in primary care is
      borderline substantial (Kappa = 0.63) for full thickness tears only. This level
      of reliability is relatively low when compared with the high reliability between
      radiologists. More experience and training of physical therapists may increase
      the reliability of diagnostic ultrasound.

PMID- 24898216
TI  - Blue rubber bleb nevus syndrome: late onset in a patient with cutaneous,
      neurological, and gastrointestinal involvement.

PMID- 24898218
TI  - Post-traumatic stress disorder in older adults: a systematic review of the
      psychotherapy treatment literature.
AB  - OBJECTIVES: Older adults represent the fastest growing segment of the US and
      industrialized populations. However, older adults have generally not been
      included in randomized clinical trials of psychotherapy for post-traumatic stress
      disorder (PTSD). This review examined reports of psychological treatment for
      trauma-related problems, primarily PTSD, in studies with samples of at least 50%
      adults aged 55 and older using standardized measures. METHODS: A systematic
      review of the literature was conducted on psychotherapy for PTSD with older
      adults using PubMed, Medline, PsychInfo, CINAHL, PILOTS, and Google Scholar.
      RESULTS: A total of 42 studies were retrieved for full review; 22 were excluded
      because they did not provide at least one outcome measure or results were not
      reported by age in the case of mixed-age samples. Of the 20 studies that met
      review criteria, there were: 13 case studies or series, three uncontrolled pilot
      studies, two randomized clinical trials, one non-randomized concurrent control
      study and one post hoc effectiveness study. Significant methodological
      limitations in the current older adult PTSD treatment outcome literature were
      found reducing its internal validity and generalizability, including non
      randomized research designs, lack of comparison conditions and small sample
      sizes. CONCLUSION: Select evidence-based interventions validated in younger and
      middle-aged populations appear acceptable and efficacious with older adults.
      There are few treatment studies on subsets of the older adult population
      including cultural and ethnic minorities, women, the oldest old (over 85), and
      those who are cognitively impaired. Implications for clinical practice and future
      research directions are discussed.

PMID- 24898219
TI  - Tree age-dependent changes in photosynthetic and respiratory CO2 exchange in
      leaves of micropropagated diploid, triploid and hybrid aspen.
AB  - The growth rate of triploid European aspen (Populus tremula L.) and hybrid aspen
      (P. tremula * Populus tremuloides Michx.) significantly exceeds that of diploid
      aspen, but the underlying physiological controls of the superior growth rates of
      these genotypes are not known. We tested the hypothesis that the superior growth
      rate of triploid and hybrid aspen reflects their greater net photosynthesis rate.
      Micropropagated clonal plants varying in age from 2.5 to 19 months were used to
      investigate the ploidy and plant age interaction. The quantum yield of net CO2
      fixation (Phi) in leaves of young 2.5-month-old hybrid aspen was lower than that
      of diploid and triploid trees. However, Phi in 19-month-old hybrid aspen was
      equal to that in triploid aspen and higher than that in diploid aspen. Phi and
      the rate of light-saturated net photosynthesis (ANS) increased with plant age,
      largely due to higher leaf dry mass per unit area in older plants. ANS in leaves
      of 19-month-old trees was highest in hybrid, medium in triploid and lowest in
      diploid aspen. Light-saturated photosynthesis had a broad temperature optimum
      between 20 and 35  degrees C. Rate of respiration in the dark (RDS) did not vary
      among the genotypes in 2.5-month-old plants, and the shape of the temperature
      response was also similar. RDS increased with plant age, but RDS was still not
      significantly different among the leaves of 19-month-old diploid and triploid
      aspen, but it was significantly lower in leaves of 19-month-old hybrid plants.
      The initial differences in the growth of plants with different ploidy were minor
      up to the age of 19 months, but during the next 2 years, the growth rate of
      hybrid aspen exceeded that of triploid plants by 2.7 times and of diploid plants
      by five times, in line with differences in ANS of 19-month-old plants of these
      species. It is suggested that differences in photosynthesis and growth became
      more pronounced with tree aging, indicating that ontogeny plays a key role in the
      expression of superior traits determining the productivity of given genotypes. 

PMID- 24898217
TI  - An efficient method for stable protein targeting in grasses (Poaceae): a case
      study in Puccinellia tenuiflora.
AB  - BACKGROUND: An efficient transformation method is lacking for most non-model
      plant species to test gene function. Therefore, subcellular localization of
      proteins of interest from non-model plants is mainly carried out through
      transient transformation in homologous cells or in heterologous cells from model
      species such as Arabidopsis. Although analysis of expression patterns in model
      organisms like yeast and Arabidopsis can provide important clues about protein
      localization, these heterologous systems may not always faithfully reflect the
      native subcellular distribution in other species. On the other hand, transient
      expression in protoplasts from species of interest has limited ability for
      detailed sub-cellular localization analysis (e.g., those involving subcellular
      fractionation or sectioning and immunodetection), as it results in heterogeneous
      populations comprised of both transformed and untransformed cells. RESULTS: We
      have developed a simple and reliable method for stable transformation of plant
      cell suspensions that are suitable for protein subcellular localization analyses
      in the non-model monocotyledonous plant Puccinellia tenuiflora. Optimization of
      protocols for obtaining suspension-cultured cells followed by Agrobacterium
      mediated genetic transformation allowed us to establish stably transformed cell
      lines, which could be maintained indefinitely in axenic culture supplied with the
      proper antibiotic. As a case study, protoplasts of transgenic cell lines stably
      transformed with an ammonium transporter-green fluorescent protein (PutAMT1;1
      GFP) fusion were successfully used for subcellular localization analyses in P.
      tenuiflora. CONCLUSIONS: We present a reliable method for the generation of
      stably transformed P. tenuiflora cell lines, which, being available in virtually
      unlimited amounts, can be conveniently used for any type of protein subcellular
      localization analysis required. Given its simplicity, the method can be used as
      reference for other non-model plant species lacking efficient regeneration
      protocols.

PMID- 24898220
TI  - Hydraulic architecture and photoinhibition influence spatial distribution of the
      arborescent palm Euterpe edulis in subtropical forests.
AB  - Physiological characteristics of saplings can be considered one of the most basic
      constraints on species distribution. The shade-tolerant arborescent palm Euterpe
      edulis Mart. is endemic to the Atlantic Forest of Argentina, Brazil and Paraguay.
      At a local scale, saplings of this species growing in native forests are absent
      in gaps. We tested the hypothesis whether sensitivity to photoinhibition or
      hydraulic architecture constrains the distribution of E. edulis saplings in sun
      exposed forest environments. Using shade houses and field studies, we evaluated
      growth, survival, hydraulic traits and the susceptibility of Photosystem II to
      photoinhibition in E. edulis saplings under different growth irradiances.
      Survival rates in exposed sites in the field were very low (a median of 7%). All
      saplings exhibited photoinhibition when exposed to high radiation levels, but
      acclimation to a high radiation environment increased the rate of recovery.
      Petiole hydraulic conductivity was similar across treatments regardless of
      whether it was expressed per petiole cross-sectional area or per leaf area. At
      the plant level, investment in conductive tissues relative to leaf area (Huber
      values) increased with increasing irradiance. Under high irradiance conditions,
      plants experienced leaf water potentials close to the turgor-loss point, and leaf
      hydraulic conductance decreased by 79% relative to its maximum value. Euterpe
      edulis saplings were able to adjust their photosynthetic traits to different
      irradiance conditions, whereas hydraulic characteristics at the leaf level did
      not change across irradiance treatments. Our results indicate that uncoupling
      between water demand and supply to leaves apparently associated with high
      resistances to water flow at leaf insertion points, in addition to small stems
      with low water storage capacity, weak stomatal control and high vulnerability of
      leaves to hydraulic dysfunction, are the main ecophysiological constraints that
      prevent the growth and survival of E. edulis saplings in gaps in the native
      forest where native lianas and bamboos show aggressive growth. 

PMID- 24898222
TI  - Sustainability of plant-based diets: back to the future.
AB  - Plant-based diets in comparison to diets rich in animal products are more
      sustainable because they use many fewer natural resources and are less taxing on
      the environment. Given the global population explosion and increase in wealth,
      there is an increased demand for foods of animal origin. Environmental data are
      rapidly accumulating on the unsustainability of current worldwide food
      consumption practices that are high in meat and dairy products. Natural
      nonrenewable resources are becoming scarce, and environmental degradation is
      rapidly increasing. At the current trends of food consumption and environmental
      changes, food security and food sustainability are on a collision course.
      Changing course (to avoid the collision) will require extreme downward shifts in
      meat and dairy consumption by large segments of the world's population. Other
      approaches such as food waste reduction and precision agriculture and/or other
      technological advances have to be simultaneously pursued; however, they are
      insufficient to make the global food system sustainable. For millennia, meatless
      diets have been advocated on the basis of values, and large segments of the world
      population have thrived on plant-based diets. "Going back" to plant-based diets
      worldwide seems to be a reasonable alternative for a sustainable future. Policies
      in favor of the global adoption of plant-based diets will simultaneously optimize
      the food supply, health, environmental, and social justice outcomes for the
      world's population. Implementing such nutrition policy is perhaps one of the most
      rational and moral paths for a sustainable future of the human race and other
      living creatures of the biosphere that we share. 

PMID- 24898221
TI  - Effect of bleaching on mercury release from amalgam fillings and antioxidant
      enzyme activities: a pilot study.
AB  - OBJECTIVE: The aim of this pilot clinical study was to determine the mercury
      release from amalgam fillings and antioxidant enzyme activities (Superoxide
      Dismutase [SOD] and Catalase[CAT] ) in body fluids after exposure to two
      different vital tooth bleaching systems. MATERIAL AND METHODS: Twenty eight
      subjects with an average age of 25.6 years (18-41) having at least two but not
      more than four Class II amalgam fillings on each quadrant arch in the mouth
      participated in the study. Baseline concentrations of mercury levels in whole
      blood, urine, and saliva were measured by a Vapor Generation Accessory connected
      to an Atomic Absorption Spectrometer. Erythrocyte enzymes, SOD, and CAT
      activities in blood were determined kinetically. Subjects were randomly assigned
      to two groups of 14 volunteers. Group 1 was treated with an at-home bleaching
      system (Opalescence PF 35% Carbamide Peroxide, Ultradent), and Group 2 was
      treated with a chemically activated office bleaching system (Opalescence Xtra
      Boost 38% Hydrogen Peroxide, Ultradent) according to the manufacturer's
      recommendations. Twenty-four hours after bleaching treatments, concentrations of
      mercury and enzymes were remeasured. RESULTS: There were no significant
      differences on mercury levels in blood, urine, and saliva before and after
      bleaching treatments (p > 0.05). No differences were also found in the level of
      antioxidant enzyme activities (SOD and CAT) before and after treatments (p >
      0.05). Mercury release did not affect the enzyme activities (p > 0.05).
      CONCLUSION: Bleaching treatments either office or home did not affect the amount
      of mercury released from amalgam fillings in blood, urine, and saliva and the
      antioxidant-enzyme activities in blood. CLINICAL SIGNIFICANCE: Bleaching
      treatments with the systems tested in this pilot study have no deleterious effect
      on the mercury release from amalgam fillings and antioxidant enzymes in body
      fluids.

PMID- 24898224
TI  - Soy foods, isoflavones, and the health of postmenopausal women.
AB  - Over the past 2 decades, soy foods have been the subject of a vast amount of
      research, primarily because they are uniquely rich sources of isoflavones.
      Isoflavones are classified as both phytoestrogens and selective estrogen receptor
      modulators. The phytoestrogenic effects of isoflavones have led some to view soy
      foods and isoflavone supplements as alternatives to conventional hormone therapy.
      However, clinical research shows that isoflavones and estrogen exert differing
      effects on a variety of health outcomes. Nevertheless, there is substantial
      evidence that soy foods have the potential to address several conditions and
      diseases associated with the menopausal transition. For example, data suggest
      that soy foods can potentially reduce ischemic heart disease through multiple
      mechanisms. Soy protein directly lowers blood low-density lipoprotein-cholesterol
      concentrations, and the soybean is low in saturated fat and a source of both
      essential fatty acids, the omega-6 fatty acid linoleic acid and the omega-3 fatty
      acid alpha-linolenic acid. In addition, soflavones improve endothelial function
      and possibly slow the progression of subclinical atherosclerosis. Isoflavone
      supplements also consistently alleviate menopausal hot flashes provided they
      contain sufficient amounts of the predominant soybean isoflavone genistein. In
      contrast, the evidence that isoflavones reduce bone loss in postmenopausal women
      is unimpressive. Whether adult soy food intake reduces breast cancer risk is
      unclear. Considerable evidence suggests that for soy to reduce risk, consumption
      during childhood and/or adolescence is required. Although concerns have been
      raised that soy food consumption may be harmful to breast cancer patients, an
      analysis in 9514 breast cancer survivors who were followed for 7.4 y found that
      higher postdiagnosis soy intake was associated with a significant 25% reduction
      in tumor recurrence. In summary, the clinical and epidemiologic data indicate
      that adding soy foods to the diet can contribute to the health of postmenopausal
      women. 

PMID- 24898223
TI  - Vegetarian diets in the Adventist Health Study 2: a review of initial published
      findings.
AB  - The Adventist Health Study 2 is a large cohort that is well suited to the study
      of the relation of vegetarian dietary patterns to health and disease risk. Here
      we review initial published findings with regard to vegetarian diets and several
      health outcomes. Vegetarian dietary patterns were associated with lower body mass
      index, lower prevalence and incidence of diabetes mellitus, lower prevalence of
      the metabolic syndrome and its component factors, lower prevalence of
      hypertension, lower all-cause mortality, and in some instances, lower risk of
      cancer. Findings with regard to factors related to vegetarian diets and bone
      health are also reviewed. These initial results show important links between
      vegetarian dietary patterns and improved health. 

PMID- 24898225
TI  - Gut microbiota and cardiometabolic outcomes: influence of dietary patterns and
      their associated components.
AB  - Many dietary patterns have been associated with cardiometabolic risk reduction. A
      commonality between these dietary patterns is the emphasis on plant-based foods.
      Studies in individuals who consume vegetarian and vegan diets have shown a
      reduced risk of cardiovascular events and incidence of diabetes. Plant-based
      dietary patterns may promote a more favorable gut microbial profile. Such diets
      are high in dietary fiber and fermentable substrate (ie, nondigestible or
      undigested carbohydrates), which are sources of metabolic fuel for gut microbial
      fermentation and, in turn, result in end products that may be used by the host
      (eg, short-chain fatty acids). These end products may have direct or indirect
      effects on modulating the health of their host. Modulation of the gut microbiota
      is an area of growing interest, and it has been suggested to have the potential
      to reduce risk factors associated with chronic diseases. Examples of dietary
      components that alter the gut microbial composition include prebiotics and
      resistant starches. Emerging evidence also suggests a potential link between
      interindividual differences in the gut microbiota and variations in physiology or
      predisposition to certain chronic disease risk factors. Alterations in the gut
      microbiota may also stimulate certain populations and may assist in
      biotransformation of bioactive components found in plant foods. Strategies to
      modify microbial communities may therefore provide a novel approach in the
      treatment and management of chronic diseases. 

PMID- 24898226
TI  - Vegetarian nutrition: past, present, future.
AB  - Early human food cultures were plant-based. Major religions such as Hinduism and
      Buddhism have recommended a vegetarian way of life since their conception. The
      recorded history of vegetarian nutrition started in the sixth century bc by
      followers of the Orphic mysteries. The Greek philosopher Pythagoras is considered
      the father of ethical vegetarianism. The Pythagorean way of life was followed by
      a number of important personalities and influenced vegetarian nutrition until the
      19th century. In Europe, vegetarian nutrition more or less disappeared during the
      Middle Ages. In the Renaissance era and in the Age of Enlightenment, various
      personalities practiced vegetarianism. The first vegetarian society was started
      in England in 1847. The International Vegetarian Society was founded in 1908 and
      the first vegan society began in 1944. Prominent vegetarians during this time
      included Sylvester Graham, John Harvey Kellogg, and Maximilian Bircher-Benner. A
      paradigm shift occurred at the turn of the 21st century. The former prejudices
      that vegetarianism leads to malnutrition were replaced by scientific evidence
      showing that vegetarian nutrition reduces the risk of most contemporary diseases.
      Today, vegetarian nutrition has a growing international following and is
      increasingly accepted. The main reasons for this trend are health concerns and
      ethical, ecologic, and social issues. The future of vegetarian nutrition is
      promising because sustainable nutrition is crucial for the well-being of
      humankind. An increasing number of people do not want animals to suffer nor do
      they want climate change; they want to avoid preventable diseases and to secure a
      livable future for generations to come. 

PMID- 24898227
TI  - Nuts in the prevention and treatment of metabolic syndrome.
AB  - Nuts are rich in many bioactive compounds that can exert beneficial effects on
      cardiovascular health. We reviewed the evidence relating nut consumption and the
      metabolic syndrome (MetS) and its components. Nuts reduce the postprandial
      glycemic response; however, long-term trials of nuts on insulin resistance and
      glycemic control in diabetic individuals are inconsistent. Epidemiologic studies
      have shown that nuts may lower the risk of diabetes incidence in women. Few
      studies have assessed the association between nuts and abdominal obesity,
      although an inverse association with body mass index and general obesity has been
      observed. Limited evidence suggests that nuts have a protective effect on blood
      pressure and endothelial function. Nuts have a cholesterol-lowering effect, but
      the relation between nuts and hypertriglyceridemia and high-density lipoprotein
      cholesterol is not well established. A recent pooled analysis of clinical trials
      showed that nuts are inversely related to triglyceride concentrations only in
      subjects with hypertriglyceridemia. An inverse association was found between the
      frequency of nut consumption and the prevalence and the incidence of MetS.
      Several trials evaluated the effect of nuts on subjects with MetS and found that
      they may have benefits in some components. Compared with a low-fat diet, a
      Mediterranean diet enriched with nuts could be beneficial for MetS management.
      The protective effects on metabolism could be explained by the modulation of
      inflammation and oxidation. Further trials are needed to clarify the role of nuts
      in MetS prevention and treatment. 

PMID- 24898228
TI  - Health benefits of plant-derived alpha-linolenic acid.
AB  - alpha-Linolenic acid (ALA) is an n-3 (omega-3) fatty acid found mostly in plant
      foods such as flaxseed, walnuts, and vegetable oils, including canola and soybean
      oils. Most of the health benefits observed for n-3 fatty acids have been
      attributed to the marine-derived long-chain n-3 fatty acids eicosapentaenoic acid
      (EPA) and docosahexaenoic acid, because of the strength of evidence from both
      epidemiologic studies and randomized controlled trials. Furthermore, the observed
      cardioprotective and other health effects of ALA have been credited to its
      precursor role in converting to EPA in the body. The promotion of fatty fish
      consumption for its documented health benefits may not be practical for those who
      are concerned with the unsustainability of marine sources or who avoid eating
      fish for a variety of reasons. ALA-rich plant sources are more abundant and may
      serve as a suitable alternate. It is therefore worthwhile to consider the
      evidence for the health benefits of ALA. The purpose of this review is to present
      the evidence from recent studies on the association between ALA and
      cardiovascular disease, type 2 diabetes, and fracture risk. The potential
      mechanisms that explain these associations will also be briefly discussed. 

PMID- 24898229
TI  - Long-term associations of nut consumption with body weight and obesity.
AB  - There is some concern that the high-fat, energy-dense content of nuts may promote
      weight gain. Nuts, however, are rich in protein and dietary fiber, which are
      associated with increased satiety. They also contain high amounts of vitamins,
      minerals, antioxidants, and phytoesterols that may confer health benefits for
      cardiovascular disease and type 2 diabetes delay and prevention. Therefore, it is
      important to determine the association between nut consumption and long-term
      weight change and disease risk to reach scientific consensus and to make evidence
      based public health recommendations. Several cross-sectional analyses have shown
      an inverse association between higher nut consumption and lower body weight. In
      addition, several independent prospective studies found that increasing nut
      consumption was associated with lower weight gain over relatively long periods of
      time. Moreover, high consumption of nuts (especially walnuts) has been associated
      with lower diabetes risk. Therefore, regular consumption (approximately one
      handful daily) of nuts over the long term, as a replacement to less healthful
      foods, can be incorporated as a component of a healthy diet for the prevention of
      obesity and type 2 diabetes. 

PMID- 24898230
TI  - Climate change mitigation and health effects of varied dietary patterns in real
      life settings throughout North America.
AB  - BACKGROUND: Greenhouse gas emissions (GHGEs) are a major consequence of our
      dietary choices. Assessments of plant-based compared with meat-based diets are
      emerging at the intersection of public health, environment, and nutrition.
      OBJECTIVES: The objective was to compare the GHGEs associated with dietary
      patterns consumed in a large population across North America and to independently
      assess mortality according to dietary patterns in the same population. DESIGN:
      Data from the Adventist Health Study 2 (AHS-2) were used to characterize the
      differential environmental and health impacts of the following 3 dietary
      patterns, which varied in the quantity of animal and plant foods: vegetarian,
      semivegetarian, and nonvegetarian. The GHGE intensities of 210 foods were
      calculated through life-cycle assessments and by using published data. The all
      cause mortality rates and all-cause mortality HRs for the AHS-2 subjects were
      adjusted for a range of lifestyle and sociodemographic factors and estimated
      according to dietary pattern. RESULTS: With the use of the nonvegetarian diet as
      a reference, the mean reductions in GHGEs for semivegetarian and vegetarian diets
      were 22% and 29%, respectively. The mortality rates for nonvegetarians,
      semivegetarians, and vegetarians were 6.66, 5.53, and 5.56 deaths per 1000 person
      years, respectively. The differences were significant. Compared with
      nonvegetarians, mortality HRs were lower for semivegetarians (0.86) and
      vegetarians (0.91). CONCLUSIONS: Moderate differences in the caloric intake of
      meat products provided nontrivial reductions in GHGEs and improved health
      outcomes, as shown through the mortality analyses. However, this does not mean
      that diets lower in GHGEs are healthy.

PMID- 24898231
TI  - Bone nutrients for vegetarians.
AB  - The process of bone mineralization and resorption is complex and is affected by
      numerous factors, including dietary constituents. Although some dietary factors
      involved in bone health, such as calcium and vitamin D, are typically associated
      with dairy products, plant-based sources of these nutrients also supply other key
      nutrients involved in bone maintenance. Some research suggests that vegetarian
      diets, especially vegan diets, are associated with lower bone mineral density
      (BMD), but this does not appear to be clinically significant. Vegan diets are not
      associated with an increased fracture risk if calcium intake is adequate. Dietary
      factors in plant-based diets that support the development and maintenance of bone
      mass include calcium, vitamin D, protein, potassium, and soy isoflavones. Other
      factors present in plant-based diets such as oxalic acid and phytic acid can
      potentially interfere with absorption and retention of calcium and thereby have a
      negative effect on BMD. Impaired vitamin B-12 status also negatively affects BMD.
      The role of protein in calcium balance is multifaceted. Overall, calcium and
      protein intakes in accord with Dietary Reference Intakes are recommended for
      vegetarians, including vegans. Fortified foods are often helpful in meeting
      recommendations for calcium and vitamin D. Plant-based diets can provide adequate
      amounts of key nutrients for bone health. 

PMID- 24898232
TI  - The road between early growth and obesity: new twists and turns.

PMID- 24898234
TI  - Plant compared with marine n-3 fatty acid effects on cardiovascular risk factors
      and outcomes: what is the verdict?
AB  - Plants provide alpha-linolenic acid [ALA; 18:3n-3 (18:3omega-3)], which can be
      converted via eicosapentaenoic acid (EPA; 20:5n-3) to docosahexaenoic acid (DHA;
      22:6n-3), which is required for normal visual and cognitive function. Dietary ALA
      is provided mainly by vegetable oils, especially soybean and rapeseed oils, but
      is destroyed by partial hydrogenation; it is also present in high amounts in
      walnuts and flaxseed. Dietary EPA and DHA are provided mainly by fish and so are
      absent from vegan diets and only present in trace amounts in vegetarian diets.
      Vegetarians and vegans have lower proportions of DHA in blood and tissue lipids
      compared with omnivores. High intakes of EPA and DHA (typically in the range of 3
      5 g/d) but not ALA have favorable effects on several cardiovascular disease (CVD)
      risk factors and have been postulated to delay arterial aging and cardiovascular
      mortality, but these intakes are beyond the range of normal dietary intake.
      Arterial stiffness, which is a measure of arterial aging, appears to be lower in
      vegans than in omnivores; and risk of CVD in vegetarians and vegans is
      approximately one-third that in omnivores. Prospective cohort studies showed
      higher intakes of EPA+DHA, and less consistently ALA, to be associated with a
      lower risk of CVD, especially fatal coronary heart disease, but meta-analyses of
      randomized controlled trials of supplementation of EPA+DHA or ALA in secondary
      prevention of CVD showed no clear benefit. Current evidence is insufficient to
      warrant advising vegans and vegetarians to supplement their diets with EPA or DHA
      for CVD prevention. 

PMID- 24898233
TI  - The causal role of breakfast in energy balance and health: a randomized
      controlled trial in lean adults.
AB  - BACKGROUND: Popular beliefs that breakfast is the most important meal of the day
      are grounded in cross-sectional observations that link breakfast to health, the
      causal nature of which remains to be explored under real-life conditions.
      OBJECTIVE: The aim was to conduct a randomized controlled trial examining causal
      links between breakfast habits and all components of energy balance in free
      living humans. DESIGN: The Bath Breakfast Project is a randomized controlled
      trial with repeated-measures at baseline and follow-up in a cohort in southwest
      England aged 21-60 y with dual-energy X-ray absorptiometry-derived fat mass
      indexes <=11 kg/m2 in women (n = 21) and <=7.5 kg/m2 in men (n = 12). Components
      of energy balance (resting metabolic rate, physical activity thermogenesis,
      energy intake) and 24-h glycemic responses were measured under free-living
      conditions with random allocation to daily breakfast (>=700 kcal before 1100) or
      extended fasting (0 kcal until 1200) for 6 wk, with baseline and follow-up
      measures of health markers (eg, hematology/biopsies). RESULTS: Contrary to
      popular belief, there was no metabolic adaptation to breakfast (eg, resting
      metabolic rate stable within 11 kcal/d), with limited subsequent suppression of
      appetite (energy intake remained 539 kcal/d greater than after fasting; 95% CI:
      157, 920 kcal/d). Rather, physical activity thermogenesis was markedly higher
      with breakfast than with fasting (442 kcal/d; 95% CI: 34, 851 kcal/d). Body mass
      and adiposity did not differ between treatments at baseline or follow-up and
      neither did adipose tissue glucose uptake or systemic indexes of cardiovascular
      health. Continuously measured glycemia was more variable during the afternoon and
      evening with fasting than with breakfast by the final week of the intervention
      (CV: 3.9%; 95% CI: 0.1%, 7.8%). CONCLUSIONS: Daily breakfast is causally linked
      to higher physical activity thermogenesis in lean adults, with greater overall
      dietary energy intake but no change in resting metabolism. Cardiovascular health
      indexes were unaffected by either of the treatments, but breakfast maintained
      more stable afternoon and evening glycemia than did fasting.

PMID- 24898235
TI  - Cancer in British vegetarians: updated analyses of 4998 incident cancers in a
      cohort of 32,491 meat eaters, 8612 fish eaters, 18,298 vegetarians, and 2246
      vegans.
AB  - BACKGROUND: Vegetarian diets might affect the risk of cancer. OBJECTIVE: The
      objective was to describe cancer incidence in vegetarians and nonvegetarians in a
      large sample in the United Kingdom. DESIGN: This was a pooled analysis of 2
      prospective studies including 61,647 British men and women comprising 32,491 meat
      eaters, 8612 fish eaters, and 20,544 vegetarians (including 2246 vegans). Cancer
      incidence was followed through nationwide cancer registries. Cancer risk by
      vegetarian status was estimated by using multivariate Cox proportional hazards
      models. RESULTS: After an average follow-up of 14.9 y, there were 4998 incident
      cancers: 3275 in meat eaters (10.1%), 520 in fish eaters (6.0%), and 1203 in
      vegetarians (5.9%). There was significant heterogeneity between dietary groups in
      risks of the following cancers: stomach cancer [RRs (95% CIs) compared with meat
      eaters: 0.62 (0.27, 1.43) in fish eaters and 0.37 (0.19, 0.69) in vegetarians; P
      heterogeneity = 0.006], colorectal cancer [RRs (95% CIs): 0.66 (0.48, 0.92) in
      fish eaters and 1.03 (0.84, 1.26) in vegetarians; P-heterogeneity = 0.033],
      cancers of the lymphatic and hematopoietic tissue [RRs (95% CIs): 0.96 (0.70,
      1.32) in fish eaters and 0.64 (0.49, 0.84) in vegetarians; P-heterogeneity =
      0.005], multiple myeloma [RRs (95% CIs): 0.77 (0.34, 1.76) in fish eaters and
      0.23 (0.09, 0.59) in vegetarians; P-heterogeneity = 0.010], and all sites
      combined [RRs (95% CIs): 0.88 (0.80, 0.97) in fish eaters and 0.88 (0.82, 0.95)
      in vegetarians; P-heterogeneity = 0.0007]. CONCLUSION: In this British
      population, the risk of some cancers is lower in fish eaters and vegetarians than
      in meat eaters.

PMID- 24898237
TI  - Vegetarian diets and bone status.
AB  - Osteoporosis is a common chronic condition associated with progressive loss of
      bone mineral density (BMD) and compromised bone strength, with increasing risk of
      fracture over time. Vegetarian diets have been shown to contain lower amounts of
      calcium, vitamin D, vitamin B-12, protein, and n-3 (omega-3) fatty acids, all of
      which have important roles in maintaining bone health. Although zinc intakes are
      not necessarily lower quantitatively, they are considerably less bioavailable in
      vegetarian diets, which suggests the need for even higher intakes to maintain
      adequate status. At the same time, healthy vegetarian diets tend to contain more
      of several protective nutrients, including magnesium, potassium, vitamin K, and
      antioxidant and anti-inflammatory phytonutrients. On balance, there is evidence
      that vegetarians, and particularly vegans, may be at greater risk of lower BMD
      and fracture. Attention to potential shortfall nutrients through the careful
      selection of foods or fortified foods or the use of supplements can help ensure
      healthy bone status to reduce fracture risk in individuals who adhere to
      vegetarian diets. 

PMID- 24898238
TI  - Glycemic index and metabolic risks: how strong is the evidence?

PMID- 24898236
TI  - The effectiveness of breakfast recommendations on weight loss: a randomized
      controlled trial.
AB  - BACKGROUND: Breakfast is associated with lower body weight in observational
      studies. Public health authorities commonly recommend breakfast consumption to
      reduce obesity, but the effectiveness of adopting these recommendations for
      reducing body weight is unknown. OBJECTIVE: We tested the relative effectiveness
      of a recommendation to eat or skip breakfast on weight loss in adults trying to
      lose weight in a free-living setting. DESIGN: We conducted a multisite, 16-wk, 3
      parallel-arm randomized controlled trial in otherwise healthy overweight and
      obese adults [body mass index (in kg/m2) between 25 and 40] aged 20-65 y. Our
      primary outcome was weight change. We compared weight change in a control group
      with weight loss in experimental groups told to eat breakfast or to skip
      breakfast [no breakfast (NB)]. Randomization was stratified by prerandomization
      breakfast eating habits. A total of 309 participants were randomly assigned.
      RESULTS: A total of 283 of the 309 participants who were randomly assigned
      completed the intervention. Treatment assignment did not have a significant
      effect on weight loss, and there was no interaction between initial breakfast
      eating status and treatment. Among skippers, mean (+/-SD) baseline weight-, age-,
      sex-, site-, and race-adjusted weight changes were -0.71 +/- 1.16, -0.76 +/-
      1.26, and -0.61 +/- 1.18 kg for the control, breakfast, and NB groups,
      respectively. Among breakfast consumers, mean (+/-SD) baseline weight-, age-, sex
      , site-, and race-adjusted weight changes were -0.53 +/- 1.16, -0.59 +/- 1.06,
      and -0.71 +/- 1.17 kg for the control, breakfast, and NB groups, respectively.
      Self-reported compliance with the recommendation was 93.6% for the breakfast
      group and 92.4% for the NB group. CONCLUSIONS: A recommendation to eat or skip
      breakfast for weight loss was effective at changing self-reported breakfast
      eating habits, but contrary to widely espoused views this had no discernable
      effect on weight loss in free-living adults who were attempting to lose weight.

PMID- 24898239
TI  - Achieving optimal n-3 fatty acid status: the vegetarian's challenge... or not.
AB  - The long chain n-3 (omega-3) fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), although originally synthesized by microorganisms in
      the oceans, are primarily obtained from the consumption of fish. Vegetarians, by
      definition, do not eat fish and thus consume virtually no EPA and DHA. Because
      conversion of the plant-derived n-3 fatty acid alpha-linolenic acid (ALA) to EPA
      and DHA is very low, n-3 tissue concentrations in vegetarians are lower than in
      omnivores. This review asks 2 questions: what is the evidence that increased n-3
      concentrations reduce the risk of cardiovascular disease in vegetarians, and, if
      it does, how can vegetarians increase their blood and tissue concentrations of
      these animal-derived fatty acids? At present, both cardiovascular risk markers
      and cardiovascular events appear to be significantly reduced in vegetarians
      compared with those in omnivores. If so, and in the absence of data to show that
      risk in vegetarians could be even lower with higher n-3 concentrations, then the
      second question becomes moot. However, the absence of evidence is not evidence of
      absence; therefore, at our present state of knowledge, increasing n-3
      concentrations is not an unreasonable goal for vegetarians. This can be
      accomplished by a variety of approaches, including increased intakes of ALA,
      consumption of stearidonic acid-enriched soybean oil (if and when it comes to the
      market), and the use of supplements containing EPA, DHA, or both derived from
      nonanimal sources (microalgae, biotech yeast, and, in the future, biotech plant
      oils). 

PMID- 24898242
TI  - A rare case of subcutaneous phaeohyphomycosis caused by a Rhytidhysteron species:
      a clinico-therapeutic experience.
AB  - BACKGROUND: Subcutaneous phaeohyphomycosis usually results from traumatic
      inoculation with the fungus and generally occurs in immunosuppressed men.
      Cladosporium, Exophiala, and Alternaria spp. are commonly implicated pathogens.
      OBJECTIVES: We present a case of subcutaneous phaeohyphomycosis caused by
      Rhytidhysteron sp. that was refractory to conventional antifungal therapy. CASE
      REPORT: A 72-year-old man with hypertension and diabetes presented with a
      multiloculated, large cystic swelling over the right dorsal foot. Laboratory
      findings and x-rays of the chest and left foot were normal. RESULTS: Adequate
      control of the patient's diabetes was achieved, and the swelling was excised
      under itraconazole/terbinafine coverage. Histology showed multiple areas of
      neutrophilic abscess, epithelioid cells, foreign body giant cells, and multiple
      septate hyphae and yeast-like cells. Dematiaceous fungus was cultured but failed
      to produce spores. Sequencing of the isolate showed a match of > 99% with
      Rhytidhysteron rufulum. The patient demonstrated no response after one year of
      therapy with itraconazole/terbinafine. Weekly infiltration of the lesion with
      liposomal amphotericin B resulted in its complete resolution within 15 weeks.
      CONCLUSIONS: Lesions of phaeohyphomycosis appear morphologically similar
      regardless of the organism implicated. Hence, their diagnosis rests entirely on
      the clinicopathological and microbiological presentation. Molecular studies may
      be required to identify a fungus if attempts to grow it in artificial culture
      media fail. Rhytidhysteron spp. are not known as pathogens in humans, and no
      treatment protocol exists. Intralesional amphotericin was highly effective in our
      patient and caused no systemic adverse effects. Voriconazole and posaconazole are
      effective against disseminated/visceral phaeohyphomycotic infections, but their
      efficacy against Rhytidhysteron spp. remains unstudied.

PMID- 24898240
TI  - Effect of moderate-dose vitamin D supplementation on insulin sensitivity in
      vitamin D-deficient non-Western immigrants in the Netherlands: a randomized
      placebo-controlled trial.
AB  - BACKGROUND: Low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been
      associated with insulin resistance, the metabolic syndrome, and type 2 diabetes.
      Because many non-Western immigrants in the Netherlands are vitamin D deficient,
      obese, and at high risk of diabetes, vitamin D supplementation may contribute to
      prevent diabetes and insulin resistance. OBJECTIVE: We examined the effect of
      vitamin D supplementation on insulin sensitivity and beta cell function in
      overweight, vitamin D-deficient, non-Western immigrants at high risk of diabetes.
      DESIGN: The study was a 16-wk, randomized, placebo-controlled trial. A total of
      130 non-Western immigrants with prediabetes (fasting glucose concentration >5.5
      mmol/L or random glucose concentration from 7.8 to 11.1 mmol/L) and vitamin D
      deficiency (serum 25[OH]D concentration <50 nmol/L) were randomly assigned after
      stratification by sex to receive either cholecalciferol (1200 IU/d) or a placebo
      for 16 wk. All participants received 500 mg Ca/d as calcium carbonate. The
      primary outcome was the difference in the area under the curve of insulin and
      glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment.
      Secondary outcomes were insulin-sensitivity variables, beta cell-function
      variables, and metabolic syndrome. RESULTS: Mean serum 25(OH)D concentrations
      increased significantly in the vitamin D compared with placebo groups. After 4 mo
      of therapy, the mean between-group difference was 38 nmol/L (95% CI: 32.1, 43.9
      nmol/L; P < 0.001). There was no significant effect on insulin sensitivity and
      beta cell function. In a post hoc analysis, when patients with diabetes at
      baseline were excluded, a significant increase in the insulinogenic index was
      observed in participants who obtained a 25(OH)D concentration >=60 nmol/L (P =
      0.040). CONCLUSIONS: Vitamin D supplementation in non-Western vitamin D-deficient
      immigrants with prediabetes did not improve insulin sensitivity or beta cell
      function or change the incidence of metabolic syndrome. However, after the
      exclusion of diabetic subjects, an improvement in the insulinogenic index was
      observed in participants who obtained a 25(OH)D concentration >=60 nmol/L. This
      trial was registered at trialregister.nl as NTR1827.

PMID- 24898241
TI  - Consumption of nuts and legumes and risk of incident ischemic heart disease,
      stroke, and diabetes: a systematic review and meta-analysis.
AB  - BACKGROUND: Relations between the consumption of nuts and legumes and risk of
      ischemic heart disease (IHD), stroke, and diabetes have not been well
      established. OBJECTIVE: We systematically investigated and quantified
      associations of nut and legume consumption with incident IHD, stroke, and
      diabetes. DESIGN: We systematically searched multiple databases to identify
      randomized controlled trials or observational studies that examined the
      relations. Studies were excluded if they reported only intermediate physiologic
      measures, soft cardiovascular outcomes, or crude risk estimates. Data were
      extracted independently and in duplicate. We assessed pooled dose-response
      relations by using a generalized least-squares trend estimation, and prespecified
      sources of heterogeneity were assessed by using metaregression. The potential for
      publication bias was explored by using funnel plots, Begg's and Egger's tests,
      and Duval and Tweedie trim-and-fill methods. RESULTS: Of 3851 abstracts, 25
      observational studies (23 prospective and 2 retrospective studies) and 2 trial
      reports met inclusion criteria and comprised 501,791 unique individuals and
      11,869 IHD, 8244 stroke, and 14,449 diabetes events. The consumption of nuts was
      inversely associated with fatal IHD (6 studies; 6749 events; RR per 4 weekly 28.4
      g servings: 0.76; 95% CI: 0.69, 0.84; I(2) = 28%), nonfatal IHD (4 studies; 2101
      events; RR: 0.78; 0.67, 0.92; I(2) = 0%), and diabetes (6 studies; 13,308 events;
      RR: 0.87; 0.81,0.94; I(2) = 22%) but not stroke (4 studies; 5544 events). Legume
      consumption was inversely associated with total IHD (5 studies; 6514 events; RR
      per 4 weekly 100-g servings: 0.86; 0.78, 0.94; I(2) = 0%) but not significantly
      associated with stroke (6 studies; 6690 events) or diabetes (2 studies; 2746
      events). A meta-regression did not identify the effect modification by age,
      duration of follow-up, study location, or study quality. Mixed evidence was seen
      for publication bias, but analyses by using the Duval and Tweedie trim-and-fill
      method did not appreciably alter results. CONCLUSION: This systematic review
      supports inverse associations between eating nuts and incident IHD and diabetes
      and eating legumes and incident IHD.

PMID- 24898243
TI  - CEPH accreditation of stand-alone baccalaureate programs: a preliminary mapping
      exercise.
AB  - The purpose of this article is to provide a brief background of quality assurance
      efforts in health education, provide a brief overview of the new Council on
      Education for Public Health (CEPH) accreditation process for stand-alone
      baccalaureate public health programs that prepare health education specialists,
      and describe the experience of two academic programs in reviewing their curricula
      for coverage of the newly approved CEPH requirements. The University of Alabama
      and the University of North Carolina Wilmington undertook a curriculum mapping
      exercise identifying which courses in their programs Introduced, Reinforced,
      and/or Covered each of the Critical Components Elements identified by CEPH. The
      mapping process is described, and recommendations for other programs considering
      accreditation under the newly adopted CEPH standards are provided. 

PMID- 24898244
TI  - Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with
      cyclical vomiting syndrome.
AB  - BACKGROUND: Aprepitant (Emend, Merck Sharp & Dohme Ltd, Haarlem, the
      Netherlands), a neurokinin-1 receptor antagonist, prevents vomiting in a range of
      conditions. No data are available on its use in children with cyclical vomiting
      syndrome (CVS). AIM: We investigated the efficacy of aprepitant as prophylactic
      treatment or acute intervention in CVS children refractory to conventional
      therapies. METHODS: Forty-one children (median age: 8 years) fulfilling NASPGHAN
      criteria treated acutely (RegA) or prophylactically (RegP) with aprepitant were
      retrospectively reviewed. Primary outcome was the clinical response (decrease in
      frequency and intensity of CVS episodes). Secondary outcomes were: number of CVS
      episodes/year, number of hospital admissions/year, CVS episode duration, number
      of vomits/h, symptom-free interval length (days), and school attendance
      percentage. The follow-up period was 18-60 months. RESULTS: Sixteen children
      received RegP and 25 RegA. One child on RegP stopped treatment due to severe
      migraine. At 12-months on intention-to-treat analysis, 13 children on RegP (81%)
      achieved either complete (3/16, 19%) or partial (10/16, 62%) clinical response.
      On RegA, 19 children (76%) had either complete (3/25, 12%) or partial (16/25,
      64%) response (P = 0.8 vs. RegP). In both RegP and RegA, there was a significant
      decrease in CVS episodes/year, hospital admission number/year, CVS episode
      length, number of vomits/h, as well as an increase in symptom-free interval
      duration and school attendance percentage. Side effects were reported only in
      RegP (5/16, 31%) including hiccough (3/16, 19%), asthenia/fatigue (2/16, 12.5%),
      increased appetite (2/16, 12.5%), mild headache (1/16, 6%) and severe migraine
      (1/16, 6%). CONCLUSION: Aprepitant appears effective for both acute and
      prophylactic management of paediatric cyclical vomiting syndrome refractory to
      conventional therapies.

PMID- 24898245
TI  - Anti-HER2 cancer therapy and cardiotoxicity.
AB  - A significant milestone in the treatment of breast cancer is the identification
      of the HER2 receptor as a drug target for cancer therapies. Trastuzumab
      (Herceptin), a monoclonal antibody that blocks the HER2 receptor, is among the
      first of such drugs approved by the US Food and Drug Administration for targeted
      cancer therapy. Clinical studies have shown that Trastuzumab significantly
      improves the overall survival of breast cancer patients. However, an unforeseen
      significant side-effect of cardiotoxicity manifested as left ventricular
      dysfunction and heart failure. Concurrent studies have demonstrated the essential
      role of the HER2 receptor in cardiac development and maintaining the
      physiological function of an adult heart. The HER2 receptor, therefore, has
      become a critical link between the oncology and cardiology fields. In addition to
      Trastuzumab, new drugs targeting the HER2 receptor, such as Lapatinib, Pertuzumab
      and Afatinib, are either approved or being evaluated in clinical trials for
      cancer therapy. With the concern of cardiotoxicity caused by HER2 inhibition, it
      becomes clear that new therapeutic strategies for preventing such cardiac side
      effects need to be developed. It is the intent of this paper to review the
      potential cardiac impact of anti-HER2 cancer therapy. 

PMID- 24898246
TI  - Endocytotic routes of cobra cardiotoxins depend on spatial distribution of
      positively charged and hydrophobic domains to target distinct types of sulfated
      glycoconjugates on cell surface.
AB  - Cobra cardiotoxins (CTX) are a family of three-fingered basic polypeptides known
      to interact with diverse targets such as heparan sulfates, sulfatides, and
      integrins on cell surfaces. After CTX bind to the membrane surface, they are
      internalized to intracellular space and exert their cytotoxicity via an unknown
      mechanism. By the combined in vitro kinetic binding, three-dimensional x-ray
      structure determination, and cell biology studies on the naturally abundant CTX
      homologues from the Taiwanese cobra, we showed that slight variations on the
      spatial distribution of positively charged or hydrophobic domains among CTX A2,
      A3, and A4 could lead to significant changes in their endocytotic pathways and
      action mechanisms via distinct sulfated glycoconjugate-mediated processes. The
      intracellular locations of these structurally similar CTX after internalization
      are shown to vary between the mitochondria and lysosomes via either dynamin2
      dependent or -independent processes with distinct membrane cholesterol
      sensitivity. Evidence is presented to suggest that the shifting between the
      sulfated glycoconjugates as distinct targets of CTX A2, A3, and A4 might play
      roles in the co-evolutionary arms race between venomous snake toxins to cope with
      different membrane repair mechanisms at the cellular levels. The sensitivity of
      endocytotic routes to the spatial distribution of positively charged or
      hydrophobic domains may provide an explanation for the diverse endocytosis
      pathways of other cell-penetrating basic polypeptides. 

PMID- 24898247
TI  - Mechanisms of toxin inhibition and transcriptional repression by Escherichia coli
      DinJ-YafQ.
AB  - Bacteria encounter environmental stresses that regulate a gene expression program
      required for adaptation and survival. Here, we report the 1.8-A crystal structure
      of the Escherichia coli toxin-antitoxin complex YafQ-(DinJ)2-YafQ, a key
      component of the stress response. The antitoxin DinJ dimer adopts a ribbon-helix
      helix motif required for transcriptional autorepression, and toxin YafQ contains
      a microbial RNase fold whose proposed active site is concealed by DinJ binding.
      Contrary to previous reports, our studies indicate that equivalent levels of
      transcriptional repression occur by direct interaction of either YafQ-(DinJ)2
      YafQ or a DinJ dimer at a single inverted repeat of its recognition sequence that
      overlaps with the -10 promoter region. Surprisingly, multiple YafQ-(DinJ)2-YafQ
      complexes binding to the operator region do not appear to amplify the extent of
      repression. Our results suggest an alternative model for transcriptional
      autorepression that may be novel to DinJ-YafQ. 

PMID- 24898248
TI  - NCLX protein, but not LETM1, mediates mitochondrial Ca2+ extrusion, thereby
      limiting Ca2+-induced NAD(P)H production and modulating matrix redox state.
AB  - Mitochondria capture and subsequently release Ca(2+) ions, thereby sensing and
      shaping cellular Ca(2+) signals. The Ca(2+) uniporter MCU mediates Ca(2+) uptake,
      whereas NCLX (mitochondrial Na/Ca exchanger) and LETM1 (leucine zipper-EF-hand
      containing transmembrane protein 1) were proposed to exchange Ca(2+) against
      Na(+) or H(+), respectively. Here we study the role of these ion exchangers in
      mitochondrial Ca(2+) extrusion and in Ca(2+)-metabolic coupling. Both NCLX and
      LETM1 proteins were expressed in HeLa cells mitochondria. The rate of
      mitochondrial Ca(2+) efflux, measured with a genetically encoded indicator during
      agonist stimulations, increased with the amplitude of mitochondrial Ca(2+)
      ([Ca(2+)]mt) elevations. NCLX overexpression enhanced the rates of Ca(2+) efflux,
      whereas increasing LETM1 levels had no impact on Ca(2+) extrusion. The
      fluorescence of the redox-sensitive probe roGFP increased during [Ca(2+)]mt
      elevations, indicating a net reduction of the matrix. This redox response was
      abolished by NCLX overexpression and restored by the Na(+)/Ca(2+) exchanger
      inhibitor CGP37157. The [Ca(2+)]mt elevations were associated with increases in
      the autofluorescence of NAD(P)H, whose amplitude was strongly reduced by NCLX
      overexpression, an effect reverted by Na(+)/Ca(2+) exchange inhibition. We
      conclude that NCLX, but not LETM1, mediates Ca(2+) extrusion from mitochondria.
      By controlling the duration of matrix Ca(2+) elevations, NCLX contributes to the
      regulation of NAD(P)H production and to the conversion of Ca(2+) signals into
      redox changes. 

PMID- 24898249
TI  - Stress-induced start codon fidelity regulates arsenite-inducible regulatory
      particle-associated protein (AIRAP) translation.
AB  - Initial steps in protein synthesis are highly regulated processes as they define
      the reading frame of the translation machinery. Eukaryotic translation initiation
      is a process facilitated by numerous factors (eIFs), aimed to form a "scanning"
      mechanism toward the initiation codon. Translation initiation of the main open
      reading frame (ORF) in an mRNA transcript has been reported to be regulated by
      upstream open reading frames (uORFs) in a manner of re-initiation. This mode of
      regulation is governed by the phosphorylation status of eIF2alpha and controlled
      by cellular stresses. Another mode of translational initiation regulation is
      leaky scanning, and this regulatory process has not been extensively studied. We
      have identified arsenite- inducible regulatory particle-associated protein
      (AIRAP) transcript to be translationally induced during arsenite stress
      conditions. AIRAP transcript contains a single uORF in a poor-kozak context.
      AIRAP translation induction is governed by means of leaky scanning and not re
      initiation. This induction of AIRAP is solely dependent on eIF1 and the uORF
      kozak context. We show that eIF1 is phosphorylated under specific conditions that
      induce protein misfolding and have biochemically characterized this site of
      phosphorylation. Our data indicate that leaky scanning like re-initiation is
      responsive to stress conditions and that leaky scanning can induce ORF
      translation by bypassing poor kozak context of a single uORF transcript.

PMID- 24898251
TI  - The mRNA of human cytoplasmic arginyl-tRNA synthetase recruits prokaryotic
      ribosomes independently.
AB  - There are two isoforms of cytoplasmic arginyl-tRNA synthetase (hcArgRS) in human
      cells. The long form is a component of the multiple aminoacyl-tRNA synthetase
      complex, and the other is an N-terminal truncated form (NhcArgRS), free in the
      cytoplasm. It has been shown that the two forms of ArgRS arise from alternative
      translational initiation in a single mRNA. The short form is produced from the
      initiation at a downstream, in-frame AUG start codon. Interestingly, our data
      suggest that the alternative translational initiation of hcArgRS mRNA also takes
      place in Escherichia coli transformants. When the gene encoding full-length
      hcArgRS was overexpressed in E. coli, two forms of hcArgRS were observed. The N
      terminal sequencing experiment identified that the short form was identical to
      the NhcArgRS in human cytoplasm. By constructing a bicistronic system, our data
      support that the mRNA encoding the N-terminal extension of hcArgRS has the
      capacity of independently recruiting E. coli ribosomes. Furthermore, two critical
      elements for recruiting prokaryotic ribosomes were identified, the "AGGA" core of
      the Shine-Dalgarno sequence and the "A-rich" sequence located just proximal to
      the alternative in-frame initiation site. Although the mechanisms of prokaryotic
      and eukaryotic translational initiation are distinct, they share some common
      features. The ability of the hcArgRS mRNA to recruit the prokaryotic ribosome may
      provide clues for shedding light on the mechanism of alternative translational
      initiation of hcArgRS mRNA in eukaryotic cells.

PMID- 24898250
TI  - Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for
      autoantibodies in inflammatory myositis.
AB  - Inflammatory and debilitating myositis and interstitial lung disease are commonly
      associated with autoantibodies (anti-Jo-1 antibodies) to cytoplasmic histidyl
      tRNA synthetase (HisRS). Anti-Jo-1 antibodies from different disease-afflicted
      patients react mostly with spatially separated epitopes in the three-dimensional
      structure of human HisRS. We noted that two HisRS splice variants (SVs) include
      these spatially separated regions, but each SV lacks the HisRS catalytic domain.
      Despite the large deletions, the two SVs cross-react with a substantial
      population of anti-Jo-l antibodies from myositis patients. Moreover, expression
      of at least one of the SVs is up-regulated in dermatomyositis patients, and cell
      based experiments show that both SVs and HisRS can be secreted. We suggest that,
      in patients with inflammatory myositis, anti-Jo-1 antibodies may have
      extracellular activity. 

PMID- 24898253
TI  - Mice deficient in the putative phospholipid flippase ATP11C exhibit altered
      erythrocyte shape, anemia, and reduced erythrocyte life span.
AB  - Transmembrane lipid transporters are believed to establish and maintain
      phospholipid asymmetry in biological membranes; however, little is known about
      the in vivo function of the specific transporters involved. Here, we report that
      developing erythrocytes from mice lacking the putative phosphatidylserine
      flippase ATP11C showed a lower rate of PS translocation in vitro compared with
      erythrocytes from wild-type littermates. Furthermore, the mutant mice had an
      elevated percentage of phosphatidylserine-exposing mature erythrocytes in the
      periphery. Although erythrocyte development in ATP11C-deficient mice was normal,
      the mature erythrocytes had an abnormal shape (stomatocytosis), and the life span
      of mature erythrocytes was shortened relative to that in control littermates,
      resulting in anemia in the mutant mice. Thus, our findings uncover an essential
      role for ATP11C in erythrocyte morphology and survival and provide a new
      candidate for the rare inherited blood disorder stomatocytosis with uncompensated
      anemia. 

PMID- 24898252
TI  - Cocrystal structures of glycyl-tRNA synthetase in complex with tRNA suggest
      multiple conformational states in glycylation.
AB  - Aminoacyl-tRNA synthetases are an ancient enzyme family that specifically charges
      tRNA molecules with cognate amino acids for protein synthesis. Glycyl-tRNA
      synthetase (GlyRS) is one of the most intriguing aminoacyl-tRNA synthetases due
      to its divergent quaternary structure and abnormal charging properties. In the
      past decade, mutations of human GlyRS (hGlyRS) were also found to be associated
      with Charcot-Marie-Tooth disease. However, the mechanisms of traditional and
      alternative functions of hGlyRS are poorly understood due to a lack of studies at
      the molecular basis. In this study we report crystal structures of wild type and
      mutant hGlyRS in complex with tRNA and with small substrates and describe the
      molecular details of enzymatic recognition of the key tRNA identity elements in
      the acceptor stem and the anticodon loop. The cocrystal structures suggest that
      insertions 1 and 3 work together with the active site in a cooperative manner to
      facilitate efficient substrate binding. Both the enzyme and tRNA molecules
      undergo significant conformational changes during glycylation. A working model of
      multiple conformations for hGlyRS catalysis is proposed based on the
      crystallographic and biochemical studies. This study provides insights into the
      catalytic pathway of hGlyRS and may also contribute to our understanding of
      Charcot-Marie-Tooth disease. 

PMID- 24898254
TI  - The retinal pigment epithelium utilizes fatty acids for ketogenesis.
AB  - Every day, shortly after light onset, photoreceptor cells shed approximately a
      tenth of their outer segment. The adjacent retinal pigment epithelial (RPE) cells
      phagocytize and digest shed photoreceptor outer segment, which provides a rich
      source of fatty acids that could be utilized as an energy substrate. From a
      microarray analysis, we found that RPE cells express particularly high levels of
      the mitochondrial HMG-CoA synthase 2 (Hmgcs2) compared with all other tissues
      (except the liver and colon), leading to the hypothesis that RPE cells, like
      hepatocytes, can produce beta-hydroxybutyrate (beta-HB) from fatty acids. Using
      primary human fetal RPE (hfRPE) cells cultured on Transwell filters with separate
      apical and basal chambers, we demonstrate that hfRPE cells can metabolize
      palmitate, a saturated fatty acid that constitutes .15% of all lipids in the
      photoreceptor outer segment, to produce beta-HB. Importantly, we found that hfRPE
      cells preferentially release beta-HB into the apical chamber and that this
      process is mediated primarily by monocarboxylate transporter isoform 1 (MCT1).
      Using a GC-MS analysis of (13)C-labeled metabolites, we showed that retinal cells
      can take up and metabolize (13)C-labeled beta-HB into various TCA cycle
      intermediates and amino acids. Collectively, our data support a novel mechanism
      of RPE-retina metabolic coupling in which RPE cells metabolize fatty acids to
      produce beta-HB, which is transported to the retina for use as a metabolic
      substrate.

PMID- 24898255
TI  - Endothelin-converting enzyme 1 and beta-arrestins exert spatiotemporal control of
      substance P-induced inflammatory signals.
AB  - Although the intracellular trafficking of G protein-coupled receptors controls
      specific signaling events, it is unclear how the spatiotemporal control of
      signaling contributes to complex pathophysiological processes such as
      inflammation. By using bioluminescence resonance energy transfer and
      superresolution microscopy, we found that substance P (SP) induces the
      association of the neurokinin 1 receptor (NK1R) with two classes of proteins that
      regulate SP signaling from plasma and endosomal membranes: the scaffolding
      proteins beta-arrestin (betaARRs) 1 and 2 and the transmembrane metallopeptidases
      ECE-1c and ECE-1d. In HEK293 cells and non-transformed human colonocytes, we
      observed that G protein-coupled receptor kinase 2 and betaARR1/2 terminate plasma
      membrane Ca(2+) signaling and initiate receptor trafficking to endosomes that is
      necessary for sustained activation of ERKs in the nucleus. betaARRs deliver the
      SP-NK1R endosomes, where ECE-1 associates with the complex, degrades SP, and
      allows the NK1R, freed from betaARRs, to recycle. Thus, both ECE-1 and betaARRs
      mediate the resensitization of NK1R Ca(2+) signaling at the plasma membrane.
      Sustained exposure of colonocytes to SP activates NF-kappaB and stimulates IL-8
      secretion. This proinflammatory signaling is unaffected by inhibition of the
      endosomal ERK pathway but is suppressed by ECE-1 inhibition or betaARR2
      knockdown. Inhibition of protein phosphatase 2A, which also contributes to
      sustained NK1R signaling at the plasma membrane, similarly attenuates IL-8
      secretion. Thus, the primary function of betaARRs and ECE-1 in SP-dependent
      inflammatory signaling is to promote resensitization, which allows the sustained
      NK1R signaling from the plasma membrane that drives inflammation. 

PMID- 24898256
TI  - Amyloid precursor protein (APP)/APP-like protein 2 (APLP2) expression is required
      to initiate endosome-nucleus-autophagosome trafficking of glypican-1-derived
      heparan sulfate.
AB  - Anhydromannose (anMan)-containing heparan sulfate (HS) derived from the
      proteoglycan glypican-1 is generated in endosomes by an endogenously or ascorbate
      induced S-nitrosothiolcatalyzed reaction. Processing of the amyloid precursor
      protein (APP) and APP-like protein 2 (APLP2) by beta- and gamma-secretases into
      amyloid beta(A) and Abeta-like peptides also takes place in these compartments.
      Moreover, anMan-containing HS suppresses the formation of toxic Abeta assemblies
      in vitro. We showed by using deconvolution immunofluorescence microscopy with an
      anMan-specific monoclonal antibody as well as (35)S labeling experiments that
      expression of APP/APLP2 is required for ascorbate-induced transport of HS from
      endosomes to the nucleus. Nuclear translocation was observed in wild-type mouse
      embryonic fibroblasts (WT MEFs), Tg2576 MEFs, and N2a neuroblastoma cells but not
      in APP(-/-) and APLP2(-/-) MEFs. Transfection of APP(-/-) cells with a vector
      encoding APP restored nuclear import of anMan-containing HS. In WT MEFs and N2a
      neuroblastoma cells exposed to beta- or gamma-secretase inhibitors, nuclear
      translocation was greatly impeded, suggesting involvement of APP/APLP2
      degradation products. In Tg2576 MEFs, the beta-inhibitor blocked transport, but
      the gamma-inhibitor did not. During chase in ascorbate- free medium, anMan
      containing HS disappeared from the nuclei of WT MEFs. Confocal immunofluorescence
      microscopy showed that they appeared in acidic, LC3-positive vesicles in keeping
      with an autophagosomal location. There was increased accumulation of anMan
      containing HS in nuclei and cytosolic vesicles upon treatment with chloroquine,
      indicating that HS was degraded in lysosomes. Manipulations of APP expression and
      processing may have deleterious effects upon HS function in the nucleus.

PMID- 24898258
TI  - Three-dimensional characterization of electrodeposited lithium microstructures
      using synchrotron X-ray phase contrast imaging.
AB  - The electrodeposition of metallic lithium is a major cause of failure in lithium
      batteries. The 3D microstructure of electrodeposited lithium 'moss' in liquid
      electrolytes has been characterised at sub-micron resolution for the first time.
      Using synchrotron X-ray phase contrast imaging we distinguish mossy metallic
      lithium microstructures from high surface area lithium salt formations by their
      contrasting X-ray attenuation. 

PMID- 24898259
TI  - Retrospective evaluation of continuation rates following a switch to subcutaneous
      methotrexate in rheumatoid arthritis patients failing to respond to or tolerate
      oral methotrexate: the MENTOR study.
AB  - OBJECTIVES: To retrospectively evaluate continuation rates in patients with
      rheumatoid arthritis (RA) who failed to respond to or tolerate oral methotrexate
      (MTX) and were subsequently switched to subcutaneous MTX (SC MTX) in routine
      clinical practice. METHOD: We conducted a retrospective review of all patients
      with RA who had been prescribed SC MTX following oral MTX at the Norfolk and
      Norwich University Hospital and had been captured on the hospital pharmacy
      database of MTX use between 17 May 2011 and 20 March 2012. Only patients for whom
      complete records were available before and for at least 6 months after the switch
      were included. RESULTS: A total of 196 patients were included in the analysis
      (75.5% women; mean age at diagnosis 47.4 years; mean duration of oral MTX therapy
      6.6 years). Patients were changed from oral to SC MTX because of lack of efficacy
      (50.5%), adverse events (43.9%), or other/unknown reasons (5.6%). High
      continuation rates were seen, with 83.0% of patients analysed still on SC MTX at
      1 year, 75.2% at 2 years, and 47.0% at 5 years. Following the switch to SC MTX, <
      10% of patients were prescribed additional biologic therapy during the first and
      second year because of an insufficient response. CONCLUSIONS: Treatment with SC
      MTX results in high continuation rates in patients who fail to respond to or
      tolerate oral MTX. Consequently, management guidelines should be adapted to
      include advice that SC MTX should be used before biologic therapy and that MTX
      failure is defined as failure only when use of SC MTX has failed.

PMID- 24898260
TI  - Lived-experience participation in nurse education: reducing stigma and enhancing
      popularity.
AB  - Mental health nursing consistently emerges as less popular than other
      specialties, and both service users and mental health practitioners are affected
      by negative attitudes. Education is fundamental to attracting students to the
      field of mental health nursing. The aim of this study was to determine the impact
      of undergraduate mental health curricula on student attitudes to people with
      mental illness, and career interest in mental health nursing. A traditional
      mental health course was compared to a course delivered by a person with lived
      experience of mental illness (and mental health service use) for its impact on
      student attitudes and career intentions in mental health nursing (cohort 1: n =
      70, cohort 2: n = 131, respectively). In both cohorts, attitudes were measured
      via self-report, before and after the course, and changes were investigated
      through within-subjects t-tests. The lived experience-led course demonstrated
      statistically-significant positive changes in intentions to pursue mental health
      nursing and a decrease in negative stereotypes, which were not observed in the
      traditional course. The valuable contribution of mental health nursing emerged in
      the traditional, but not lived-experience-led, programmes. These findings support
      the value of an academic with lived experience of mental health challenges in
      promoting attraction to mental health nursing as a career option.

PMID- 24898257
TI  - The nuclear receptor peroxisome proliferator-activated receptor-beta/delta
      (PPARbeta/delta) promotes oncogene-induced cellular senescence through repression
      of endoplasmic reticulum stress.
AB  - Endoplasmic reticulum (ER) stress and ER stress-associated unfolded protein
      response (UPR) can promote cancer cell survival, but it remains unclear whether
      they can influence oncogene-induced senescence. The present study examined the
      role of ER stress in senescence using oncogene-dependent models. Increased ER
      stress attenuated senescence in part by up-regulating phosphorylated protein
      kinase B (p-AKT) and decreasing phosphorylated extracellular signal-regulated
      kinase (p-ERK). A positive feed forward loop between p-AKT, ER stress, and UPR
      was discovered whereby a transient increase of ER stress caused reduced
      senescence and promotion of tumorigenesis. Decreased ER stress was further
      correlated with increased senescence in both mouse and human tumors.
      Interestingly, H-RAS-expressing Pparbeta/delta null cells and tumors having
      increased cell proliferation exhibited enhanced ER stress, decreased cellular
      senescence, and/or enhanced tumorigenicity. Collectively, these results
      demonstrate a new role for ER stress and UPR that attenuates H-RAS-induced
      senescence and suggest that PPARbeta/delta can repress this oncogene-induced ER
      stress to promote senescence in accordance with its role as a tumor modifier that
      suppresses carcinogenesis. 

PMID- 24898261
TI  - Ultrasensitive detection of ATP based on ATP regeneration amplification and its
      application in cell homogenate and human serum.
AB  - A conformation-switching aptamer molecule that could be circularized without
      ligation DNA was designed. Pyrophosphate (PPi) was converted to ATP, resulting in
      higher signals for ATP detection. Meanwhile, the method has significant
      implications for real applications. 

PMID- 24898262
TI  - Full nursing potential: a concept clarification.
AB  - AIM: Report a clarification of the concept of full nursing potential. BACKGROUND:
      The Institute of Medicine and World Health Organization have called for the
      removal of barriers to allow nurses to practice to the fullest extent of their
      education and experience. Terms analogous to full nursing potential are prominent
      in the nursing literature. However, to date, there has been no clear definition
      of full nursing potential. DESIGN: Concept clarification. DATA SOURCES: PubMed,
      Cumulative Index to Nursing and Allied Health Literature, Google Scholar, and
      Ovid were searched for terms analogous to full nursing potential (nursing
      utilization, scope of practice, roles, and actualization). METHODS: Norris'
      concept clarification method was used to clarify the concept of full nursing
      potential. Following repeated observation and description, the concept was
      systematized, and a model and an operational definition were developed. RESULTS:
      Systemization of the concept led to the proposal of the following definition:
      Full nursing potential is a dynamic state in which government regulations,
      institutional policies, adequate education, personal experience, environmental
      factors, and personal traits culminate to foster the essence of nursing, enabling
      nurses to deliver high-quality, patient-centered care and promote equitable
      social systems. CONCLUSION: Realization of full nursing potential can help foster
      patient-centered care while combating social injustice.

PMID- 24898263
TI  - Ablation of typical atrial flutter using the novel MediGuide 3D catheter tracking
      system: a review of the literature.
AB  - The MediGuideTM system is a novel technology for non-fluoroscopic 3D catheter
      tracking during cardiovascular electrophysiological procedures. The system allows
      for precise catheter visualization on pre-recorded conventional fluoroscopy
      images, with significant reduction of fluoroscopy exposure. This might translate
      into improved safety for both patients and operators, without affecting the
      procedural efficacy. Preliminary data suggest that the MediGuide technology is at
      least as safe and effective as conventional systems for mapping and catheter
      ablation of a variety of supraventricular arrhythmias, with a significantly
      reduced fluoroscopy exposure. In this review, the authors summarize data from the
      available literature data on catheter ablation of typical atrial flutter using
      the novel MediGuide technology. 

PMID- 24898264
TI  - The implications of the feminization of the primary care physician workforce on
      service supply: a systematic review.
AB  - There is a widespread perception that the increasing proportion of female
      physicians in most developed countries is contributing to a primary care service
      shortage because females work less and provide less patient care compared with
      their male counterparts. There has, however, been no comprehensive investigation
      of the effects of primary care physician (PCP) workforce feminization on service
      supply. We undertook a systematic review to examine the current evidence that
      quantifies the effect of feminization on time spent working, intensity and scope
      of work, and practice characteristics. We searched Medline, Embase, and Web of
      Science from 1991 to 2013 using variations of the terms 'primary care', 'women',
      'manpower', and 'supply and distribution'; screened the abstracts of all
      articles; and entered those meeting our inclusion criteria into a data
      abstraction tool. Original research comparing male to female PCPs on measures of
      years of practice, time spent working, intensity of work, scope of work, or
      practice characteristics was included. We screened 1,271 unique abstracts and
      selected 74 studies for full-text review. Of these, 34 met the inclusion
      criteria. Years of practice, hours of work, intensity of work, scope of work, and
      practice characteristics featured in 12%, 53%, 42%, 50%, and 21% of studies
      respectively. Female PCPs self-report fewer hours of work than male PCPs, have
      fewer patient encounters, and deliver fewer services, but spend longer with their
      patients during a contact and deal with more separate presenting problems in one
      visit. They write fewer prescriptions but refer to diagnostic services and
      specialist physicians more often. The studies included in this review suggest
      that the feminization of the workforce is likely to have a small negative impact
      on the availability of primary health care services, and that the drivers of
      observed differences between male and female PCPs are complex and nuanced. The
      true scale of the impact of these findings on future effective physician supply
      is difficult to determine with currently available evidence, given that few
      studies looked at trends over time, and results from those that did are
      inconsistent. Additional research examining gender differences in practice
      patterns and scope of work is warranted. 

PMID- 24898265
TI  - Maternal-fetal disposition of glyburide in pregnant mice is dependent on
      gestational age.
AB  - Gestational diabetes mellitus is a major complication of human pregnancy. The
      oral clearance (CL) of glyburide, an oral antidiabetic drug, increases 2-fold in
      pregnant women during late gestation versus nonpregnant controls. In this study,
      we examined gestational age-dependent changes in maternal-fetal pharmacokinetics
      (PK) of glyburide and metabolites in a pregnant mouse model. Nonpregnant and
      pregnant FVB mice were given glyburide by retro-orbital injection. Maternal
      plasma was collected over 240 minutes on gestation days (gd) 0, 7.5, 10, 15, and
      19; fetuses were collected on gd 15 and 19. Glyburide and metabolites were
      quantified using high-performance liquid chromatography-mass spectrometry, and PK
      analyses were performed using a pooled data bootstrap approach. Maternal CL of
      glyburide increased approximately 2-fold on gd 10, 15, and 19 compared with
      nonpregnant controls. Intrinsic CL of glyburide in maternal liver microsomes also
      increased as gestation progressed. Maternal metabolite/glyburide area under the
      curve ratios were generally unchanged or slightly decreased throughout gestation.
      Total fetal exposure to glyburide was <5% of maternal plasma exposure, and was
      doubled on gd 19 versus gd 15. Fetal metabolite concentrations were below the
      limit of assay detection. This is the first evidence of gestational age-dependent
      changes in glyburide PK. Increased maternal glyburide clearance during gestation
      is attributable to increased hepatic metabolism. Metabolite elimination may also
      increase during pregnancy. In the mouse model, fetal exposure to glyburide is
      gestational age-dependent and low compared with maternal plasma exposure. These
      results indicate that maternal glyburide therapeutic strategies may require
      adjustments in a gestational age-dependent manner if these same changes occur in
      humans. 

PMID- 24898267
TI  - The [18F]FDG MUPET readout of a brain activation model to evaluate the
      metabotropic glutamate receptor 2 positive allosteric modulator JNJ-42153605.
AB  - Using [(18)F]fluorodeoxyglucose MU-positron emission tomography ([(18)F]FDG
      MUPET), we compared subanesthetic doses of memantine and ketamine on their
      potential to induce increases in brain activation. We also studied the reversal
      effect of the well-known metabotropic glutamate receptor (mGluR)-2/3 agonist
      LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6
      dicarboxylic acid] and the novel mGluR2 positive allosteric modulator (PAM) JNJ
      42153605 [3-cylcopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl
      [1,2,4] triazolo[4,3-a]pyridine]. First, rats (n = 12) were subjected to LY404039
      (10 mg/kg s.c.) or vehicle, 30 minutes prior to saline, ketamine (30 mg/kg i.p.),
      or memantine (20 mg/kg i.p.). Second, rats (n = 12) were subjected to 2.5 mg/kg
      or 10 mg/kg mGluR2 PAM JNJ-42153605 or vehicle (s.c.), 30 minutes prior to
      memantine (20 mg/kg i.p.) or saline. Fifteen minutes later, [(18)F]FDG was
      injected (37 MBq i.v.) followed by a MUPET/computed tomography scan. The increase
      due to memantine is significant for all relevant brain areas, whereas for
      ketamine this is not the case. Standard uptake values (SUVs) of the LY404039
      pretreated and memantine-challenged group display a full reversal. Pretreatment
      with JNJ-42153605 also dose-dependently decreases SUV with a full reversal as
      well (for 10 mg/kg). Moreover, specificity of JNJ-42153605 is reached at this
      dose. In conclusion, this MUPET experiment clearly indicates that subanesthetic
      doses of memantine induce significant increases of [(18)F]FDG SUVs in discrete
      brain areas and that the novel mGluR2 PAM has the capacity to dose-dependently
      and specifically reverse memantine-induced brain activation. 

PMID- 24898266
TI  - Casein kinase II regulates N-methyl-D-aspartate receptor activity in spinal cords
      and pain hypersensitivity induced by nerve injury.
AB  - Increased N-methyl-d-aspartate receptor (NMDAR) activity and phosphorylation in
      the spinal cord are critically involved in the synaptic plasticity and central
      sensitization associated with neuropathic pain. However, the mechanisms
      underlying increased NMDAR activity in neuropathic pain conditions remain poorly
      understood. Here we show that peripheral nerve injury induces a large GluN2A
      mediated increase in NMDAR activity in spinal lamina II, but not lamina I,
      neurons. However, NMDAR currents in spinal dorsal horn neurons are not
      significantly altered in rat models of diabetic neuropathic pain and
      resiniferatoxin-induced painful neuropathy (postherpedic neuralgia). Inhibition
      of protein tyrosine kinases or protein kinase C has little effect on NMDAR
      currents potentiated by nerve injury. Strikingly, casein kinase II (CK2)
      inhibitors normalize increased NMDAR currents of dorsal horn neurons in nerve
      injured rats. In addition, inhibition of calcineurin, but not protein phosphatase
      1/2A, augments NMDAR currents only in control rats. CK2 inhibition blocks the
      increase in spinal NMDAR activity by the calcineurin inhibitor in control rats.
      Furthermore, nerve injury significantly increases CK2alpha and CK2beta protein
      levels in the spinal cord. In addition, inhibition of CK2 or CK2beta knockdown at
      the spinal level substantially reverses pain hypersensitivity induced by nerve
      injury. Our study indicates that neuropathic pain conditions with different
      etiologies do not share the same mechanisms, and increased spinal NMDAR activity
      is distinctly associated with traumatic nerve injury. CK2 plays a prominent role
      in the potentiation of NMDAR activity in the spinal dorsal horn and may represent
      a new target for treatments of chronic pain caused by nerve injury. 

PMID- 24898269
TI  - Ultrabright continuously tunable terahertz-wave generation at room temperature.
AB  - The hottest frequency region in terms of research currently lies in the
      'frequency gap' region between microwaves and infrared: terahertz waves. Although
      new methods for generating terahertz radiation have been developed, most sources
      cannot generate high-brightness terahertz beams. Here we demonstrate the
      generation of ultrabright terahertz waves (brightness ~0.2 GW/sr.cm(2),
      brightness temperature of ~10(18) K, peak power of >50 kW) using parametric
      wavelength conversion in a nonlinear crystal; this is brighter than many
      specialized sources such as far-infrared free-electron lasers (~10(16) K, ~2 kW).
      We revealed novel parametric wavelength conversion using stimulated Raman
      scattering in LiNbO3 without stimulated Brillouin scattering using recently
      developed microchip laser. Furthermore, nonlinear up-conversion techniques allow
      the intense terahertz waves to be visualized and their frequency determined.
      These results are very promising for extending applied research into the
      terahertz region, and we expect that this source will open up new research fields
      such as nonlinear optics in the terahertz region. 

PMID- 24898268
TI  - 3,3'-diindolylmethane ameliorates experimental autoimmune encephalomyelitis by
      promoting cell cycle arrest and apoptosis in activated T cells through microRNA
      signaling pathways.
AB  - 3,3'-Diindolylmethane (DIM) is a naturally derived indole found in cruciferous
      vegetables that has great potential as a novel and effective therapeutic agent.
      In the current study, we investigated the effects of DIM post-treatment on the
      regulation of activated T cells during the development of experimental autoimmune
      encephalomyelitis (EAE), a murine model of multiple sclerosis. We demonstrated
      that the administration of DIM 10 days after EAE induction was effective at
      ameliorating disease parameters, including inflammation and central nervous
      system cellular infiltration. MicroRNA (miRNA) microarray analysis revealed an
      altered miRNA profile in brain infiltrating CD4(+) T cells following DIM post
      treatment of EAE mice. Additionally, bioinformatics analysis suggested the
      involvement of DIM-induced miRNAs in pathways and processes that halt cell cycle
      progression and promote apoptosis. Additional studies confirmed that DIM impacted
      these cellular processes in activated T cells. Further evidence indicated that
      DIM treatment significantly upregulated several miRNAs (miR-200c, miR-146a, miR
      16, miR-93, and miR-22) in brain CD4(+) T cells during EAE while suppressing
      their associated target genes. Similarly, we found that overexpression of miR-16
      in primary CD4(+) T cells led to significant downregulation of both mRNA and
      protein levels of cyclin E1 and B-cell lymphoma-2, which play important roles in
      regulating cell cycle progression and apoptosis. Collectively, these studies
      demonstrate that DIM post-treatment leads to the amelioration of EAE development
      by suppressing T-cell responses through the induction of select miRNAs that
      control cell cycle progression and mediate apoptosis. 

PMID- 24898270
TI  - Depression with atypical features and increase in obesity, body mass index, waist
      circumference, and fat mass: a prospective, population-based study.
AB  - IMPORTANCE: Depression and obesity are 2 prevalent disorders that have been
      repeatedly shown to be associated. However, the mechanisms and temporal sequence
      underlying this association are poorly understood. OBJECTIVE: To determine
      whether the subtypes of major depressive disorder (MDD; melancholic, atypical,
      combined, or unspecified) are predictive of adiposity in terms of the incidence
      of obesity and changes in body mass index (calculated as weight in kilograms
      divided by height in meters squared), waist circumference, and fat mass. DESIGN,
      SETTING, AND PARTICIPANTS: This prospective population-based cohort study, CoLaus
      (Cohorte Lausannoise)/PsyCoLaus (Psychiatric arm of the CoLaus Study), with 5.5
      years of follow-up included 3054 randomly selected residents (mean age, 49.7
      years; 53.1% were women) of the city of Lausanne, Switzerland (according to the
      civil register), aged 35 to 66 years in 2003, who accepted the physical and
      psychiatric baseline and physical follow-up evaluations. EXPOSURES: Depression
      subtypes according to the DSM-IV. Diagnostic criteria at baseline and follow-up,
      as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use
      and physical activity), and medication, were elicited using the semistructured
      Diagnostic Interview for Genetic Studies. MAIN OUTCOMES AND MEASURES: Changes in
      body mass index, waist circumference, and fat mass during the follow-up period,
      in percentage of the baseline value, and the incidence of obesity during the
      follow-up period among nonobese participants at baseline. Weight, height, waist
      circumference, and body fat (bioimpedance) were measured at baseline and follow
      up by trained field interviewers. RESULTS: Only participants with the atypical
      subtype of MDD at baseline revealed a higher increase in adiposity during follow
      up than participants without MDD. The associations between this MDD subtype and
      body mass index (beta = 3.19; 95% CI, 1.50-4.88), incidence of obesity (odds
      ratio, 3.75; 95% CI, 1.24-11.35), waist circumference in both sexes (beta = 2.44;
      95% CI, 0.21-4.66), and fat mass in men (beta = 16.36; 95% CI, 4.81-27.92)
      remained significant after adjustments for a wide range of possible cofounding.
      CONCLUSIONS AND RELEVANCE: The atypical subtype of MDD is a strong predictor of
      obesity. This emphasizes the need to identify individuals with this subtype of
      MDD in both clinical and research settings. Therapeutic measures to diminish the
      consequences of increased appetite during depressive episodes with atypical
      features are advocated.

PMID- 24898271
TI  - Evidence for sex-specific selection in brain: a case study of the nine-spined
      stickleback.
AB  - Theory predicts that the sex making greater investments into reproductive
      behaviours demands higher cognitive ability, and as a consequence, larger brains
      or brain parts. Further, the resulting sexual dimorphism can differ between
      populations adapted to different environments, or among individuals developing
      under different environmental conditions. In the nine-spine stickleback
      (Pungitius pungitius), males perform nest building, courtship, territory defence
      and parental care, whereas females perform mate choice and produce eggs. Also,
      predation-adapted marine and competition-adapted pond populations have diverged
      in a series of ecologically relevant traits, including the level of phenotypic
      plasticity. Here, we studied sexual dimorphism in brain size and architecture in
      nine-spined stickleback from marine and pond populations reared in a factorial
      experiment with predation and food treatments in a common garden experiment.
      Males had relatively larger brains, larger telencephala, cerebella and
      hypothalami (6-16% divergence) than females, irrespective of habitat. Females
      tended to have larger bulbi olfactorii than males (13%) in the high food
      treatment, whereas no such difference was found in the low food treatment. The
      strong sexual dimorphism in brain architecture implies that the different
      reproductive allocation strategies (behaviour vs. egg production) select for
      different investments into the costly brains between males and females. The lack
      of habitat dependence in brain sexual dimorphism suggests that the sex-specific
      selection forces on brains differ only negligibly between habitats. Although
      significance of the observed sex-specific brain plasticity in the size of bulbus
      olfactorius remains unclear, it demonstrates the potential for sex-specific
      neural plasticity. 

PMID- 24898272
TI  - Four-year retention and risk factors for attrition among members of community ART
      groups in Tete, Mozambique.
AB  - OBJECTIVE: Community ART groups (CAG), peer support groups involved in community
      ART distribution and mutual psychosocial support, were piloted to respond to
      staggering antiretroviral treatment (ART) attrition in Mozambique. To understand
      the impact of CAG on long-term retention, we estimated mortality and lost-to
      follow-up (LTFU) rates and assessed predictors for attrition. METHODS:
      Retrospective cohort study. Kaplan-Meier techniques were used to estimate
      mortality and LTFU in CAG. Individual- and CAG-level predictors of attrition were
      assessed using a multivariable Cox proportional hazards model, adjusted for site
      level clustering. RESULTS: Mortality and LTFU rates among 5729 CAG members were,
      respectively, 2.1 and 0.1 per 100 person-years. Retention was 97.7% at 12 months,
      96.0% at 24 months, 93.4% at 36 months and 91.8% at 48 months. At individual
      level, attrition in CAG was significantly associated with immunosuppression when
      joining a CAG, and being male. At CAG level, attrition was associated with lack
      of rotational representation at the clinic, lack of a regular CD4 count among
      fellow members and linkage to a rural or district clinic compared with linkage to
      a peri-urban clinic. CONCLUSIONS: Long-term retention in this community-based ART
      model compares favourably with published data on stable ART patients.
      Nevertheless, to reduce attrition, further efforts need to be made to enroll
      patients earlier on ART, promote health-seeking behaviour, especially for men,
      promote a strong peer dynamic to assure rotational representation at the clinic
      and regular CD4 follow-up and reinforce referral of sick patients.

PMID- 24898273
TI  - Reduced prevalence of Giardia duodenalis in iron-deficient Rwandan children.
AB  - OBJECTIVE: Acute symptomatic infection with Giardia duodenalis impairs iron
      absorption, but iron deficiency may protect against infections caused by various
      micro-organisms including parasites. We therefore examined the association of G.
      duodenalis infection and iron deficiency in 575 Rwandan children under 5 years of
      age. METHODS: Giardia duodenalis infection was diagnosed by triplicate microscopy
      and PCR assays, and iron deficiency was defined as a ferritin concentration <12
      ng/ml. RESULTS: Largely asymptomatic G. duodenalis infection was seen in 65.3% of
      the children and iron deficiency in 17.4%. G. duodenalis infection was less
      common in iron-deficient children (51%) than in non-deficient children (68%, P =
      0.002). In multivariate analysis, the odds of G. duodenalis infection were almost
      halved in iron-deficient children (adjusted odds ratio, 0.54; 95% confidence
      interval, 0.33-0.86). CONCLUSION: In this highly endemic setting, there was no
      evidence that Giardia infection impairs iron status. Rather, iron deficiency
      appeared to protect against infection with this parasite.

PMID- 24898276
TI  - An unusual chiral 3D inorganic connectivity featuring a {Pb18} wheel: rapid and
      highly selective and sensitive sensing of Co(II).
AB  - A pair of enantiomorphic frameworks featuring rare chiral 3D inorganic
      connectivity and a {Pb18} wheel, has been obtained via spontaneous resolution.
      They exhibit rapid and highly selective and sensitive sensing of Co(2+) ions. 

PMID- 24898275
TI  - Future burn care: balancing the relationship between cost and quality.

PMID- 24898274
TI  - Vector competence of Culex pipiens quinquefasciatus (Diptera: Culicidae) for West
      Nile virus isolates from Florida.
AB  - OBJECTIVES: To assess vector competence (infection, dissemination and
      transmission) of Culex pipiens quinquefasciatus for Florida (FL) West Nile virus
      (WNV) isolates. METHODS: West Nile virus isolates (WN-FL-03: NY99 genotype; WN-FL
      05-558, WN-FL-05-2186, WN-FL-05-510: WN02 genotype) collected from different
      regions of FL were used for vector competence experiments in Cx. p.
      quinquefasciatus from Alachua County and Indian River County in FL. Mosquitoes
      from both colonies were fed blood containing 7.9 +/- 0.2 log10 plaque-forming
      units WNV/ml +/- SE and incubated at 28  degrees C for 14 days. Vector
      competence, including rates of infection, dissemination, and transmission, was
      compared between colonies for WN-FL-03 using chi-squared. Virus titres in bodies,
      legs and saliva were compared using anova. Daily measurements of in vitro
      replication of WNV isolates were evaluated in Vero cells so that a standardised
      virus dose for each isolate could be delivered to mosquitoes. RESULTS: Infection
      and dissemination rates were high (>= 95%) and not affected by isolate or colony
      (infection, P = 0.679; dissemination, P = 0.799). Transmission rates were low (<=
      20%), detected in one colony and affected by isolate (P = 0.008). Body and leg
      titres differed between isolates (body titre, P = 0.031; leg titre, P = 0.044)
      and colonies (body titre, P = 0.001; leg titre, P = 0.013) while saliva titre did
      not differ between isolates (P = 0.462). CONCLUSIONS: Variation in vector
      competence of mosquito populations may be attributed, in part, to exposures to
      WNV with genetic differences leading to different rates of replication in
      mosquitoes. Evaluation of vector competence for different WNV isolates may help
      us understand vector-virus interactions and, hence, the role of vectors in
      complex virus transmission cycles in nature.

PMID- 24898278
TI  - Chronic lymphedema in renal transplant recipients under immunosuppression with
      sirolimus: presentation of 2 cases.

PMID- 24898277
TI  - The preferences of users of electronic medical records in hospitals: quantifying
      the relative importance of barriers and facilitators of an innovation.
AB  - BACKGROUND: Currently electronic medical records (EMRs) are implemented in
      hospitals, because of expected benefits for quality and safety of care. However
      the implementation processes are not unproblematic and are slower than needed.
      Many of the barriers and facilitators of the adoption of EMRs are identified, but
      the relative importance of these factors is still undetermined. This paper
      quantifies the relative importance of known barriers and facilitators of EMR,
      experienced by the users (i.e., nurses and physicians in hospitals). METHODS: A
      discrete choice experiment (DCE) was conducted among physicians and nurses.
      Participants answered ten choice sets containing two scenarios. Each scenario
      included attributes that were based on previously identified barriers in the
      literature: data entry hardware, technical support, attitude head of department,
      performance feedback, flexibility of interface, and decision support. Mixed
      Multinomial Logit analysis was used to determine the relative importance of the
      attributes. RESULTS: Data on 148 nurses and 150 physicians showed that high
      flexibility of the interface was the factor with highest relative importance in
      their preference to use an EMR. For nurses this attribute was followed by support
      from the head of department, presence of performance feedback from the EMR and
      presence of decisions support. While for physicians this ordering was different:
      presence of decision support was relatively more important than performance
      feedback and support from the head of department. CONCLUSION: Considering the
      prominent wish of all the intended users for a flexible interface, currently used
      EMRs only partially comply with the needs of the users, indicating the need for
      closer incorporation of user needs during development stages of EMRs. The
      differences in priorities amongst nurses and physicians show that different users
      have different needs during the implementation of innovations. Hospital
      management may use this information to design implementation trajectories to fit
      the needs of various user groups.

PMID- 24898279
TI  - Expression of the glucose-sensing receptor T1R3 in pancreatic islet: changes in
      the expression levels in various nutritional and metabolic states.
AB  - We reported recently that the taste type 1 receptor 3 (T1R3), a subunit of the
      sweet taste receptor, functions as a cell-surface glucose-sensing receptor in
      pancreatic beta-cells. In the present study, we investigated the expression of
      T1R3 in pancreatic islets. mRNA for T1R2 and T1R3 was detected in mouse
      pancreatic islets. Quantitatively, the mRNA expression level of T1R2 was less
      than 1% of that of T1R3. Immunohistochemically, T1R3 was abundantly expressed in
      mouse islets whereas T1R2 was barely detected. Most immunoreactive T1R3 was
      colocalized with insulin and almost all beta-cells were positive for T1R3. In
      addition, T1R3 was expressed in some portion of alpha-cells. Immunoreactivity of
      T1R3 in beta-cells was markedly reduced in fed mice compared to those in fasting
      mice. In contrast, mRNA for T1R3 was not different in islets of fasting and fed
      mice. Glucose-induced insulin-secretion was higher in islets obtained from
      fasting mice compared to those from fed mice. The expression of T1R3 was markedly
      reduced in islets of ob/ob mice compared to those of control mice. Similarly, the
      expression of T1R3 was reduced in islet of db/db mice. In addition, the
      expression of T1R3 was markedly reduced in beta-cells of fatty diabetic rats and
      GK rats, models of obese and non-obese type 2 diabetes, respectively. These
      results indicate that T1R3 is expressed mainly in beta-cells and the expression
      levels are different depending upon the nutritional and metabolic conditions. 

PMID- 24898280
TI  - Tensor hydraulic conductivity estimation for heterogeneous aquifers under unknown
      boundary conditions.
AB  - A physically based inverse method is developed using hybrid formulation and
      coordinate transform to simultaneously estimate hydraulic conductivity tensors,
      steady-state flow field, and boundary conditions for a confined aquifer under
      ambient flow or pumping condition. Unlike existing indirect inversion techniques,
      the physically based method does not require forward simulations to assess model
      data misfits. It imposes continuity of hydraulic head and Darcy fluxes in the
      model domain while incorporating observations (hydraulic heads, Darcy fluxes, or
      well rates) at measurement locations. Given sufficient measurements, it yields a
      well-posed inverse system of equations that can be solved efficiently with coarse
      grids and nonlinear optimization. When pumping and injection are active, well
      rates are used as measurements and flux sampling is not needed. The method is
      successfully tested on synthetic aquifer problems with regular and irregular
      geometries, different hydrofacies and flow patterns, and increasing conductivity
      anisotropy ratios. All problems yield stable inverse solutions under increasing
      head measurement errors. For a given set of observations, inversion accuracy is
      strongly affected by the conductivity anisotropy ratio. Conductivity estimation
      is also affected by flow pattern: within a hydrofacies, when Darcy flux component
      is very small, the corresponding directional conductivity perpendicular to
      streamlines becomes less identifiable. Finally, inversion is successful even if
      the location of aquifer boundaries is unknown. In this case, the inversion domain
      is defined by the location of the measurements. 

PMID- 24898281
TI  - Leadership in medicine: do we need a new approach?
AB  - All of us who practice medicine are called upon to exercise leadership in a
      variety of roles; in some instances, a position of leadership will be enshrined
      in a title, whereas in others the role will be less outwardly apparent but no
      less critical. Fundamental to success in leadership in modern medicine is the
      recognition that we now work in teams whose members are interdependent; leaders
      must learn the skills necessary to motivate, guide, and develop teams and team
      members. Communication is a key skill for the leader of today; effective
      communication, its various methodologies and styles, can be learned and improved
      upon. 

PMID- 24898282
TI  - Differences in lipid profiles in two Hispanic ischemic stroke populations.
AB  - BACKGROUND AND PURPOSE: The study aims to compare lipid profiles among ischemic
      stroke patients in a predominantly Caribbean-Hispanic population in Miami and a
      Mestizo Hispanic population in Mexico City. METHODS: We analyzed ischemic stroke
      Hispanic patients with complete baseline fasting lipid profile enrolled
      contemporaneously in the prospective registries of two tertiary care teaching
      hospitals in Mexico City and Miami. Demographic characteristics, risk factors,
      medications, ischemic stroke subtype, and first fasting lipid profile were
      compared. Vascular risk factor definitions were standardized. Multiple linear
      regression analysis was performed to compare lipid fractions. RESULTS: A total of
      324 patients from Mexico and 236 from Miami were analyzed. Mexicans were
      significantly younger (58 . 1 vs. 67 . 4 years), had a lower frequency of
      hypertension (53 . 4% vs. 79 . 7%), and lower body mass index (27 vs. 28 . 5).
      There was a trend toward greater prevalence of diabetes in Mexicans (31 . 5 vs.
      24 . 6%, P = 0 . 07). Statin use at the time of ischemic stroke was more common
      in Miami Hispanics (18 . 6 vs. 9 . 4%). Mexicans had lower total cholesterol
      levels (169 . 9 +/- 46 . 1 vs. 179 . 9 +/- 48 . 4 mg/dl), lower low-density
      lipoprotein (92 . 3 +/- 37 . 1 vs. 108 . 2 +/- 40 . 8 mg/dl), and higher
      triglyceride levels (166 . 9 +/- 123 . 9 vs. 149 . 2 +/- 115 . 2 mg/dl). These
      differences remained significant after adjusting for age, gender, hypertension,
      diabetes, body mass index, smoking, ischemic stroke subtype, and statin use.
      CONCLUSION: We found significant differences in lipid fractions in Hispanic
      ischemic stroke patients, with lower total cholesterol and low-density
      lipoprotein, and higher triglyceride levels in Mexicans. These findings highlight
      the heterogeneity of dyslipidemia among the Hispanic race-ethnic group and may
      lead to different secondary prevention strategies.

PMID- 24898283
TI  - Chlamydia pneumoniae disrupts lipid metabolism in human umbilical vein
      endothelial cells.
AB  - Atherosclerosis is well established as a chronic inflammatory disorder, and
      Chlamydia pneumoniae is considered to be a risk factor for atherosclerotic
      development. Endothelial dysfunction, caused by oxidized low-density lipoprotein
      (ox-LDL) is an early atherosclerotic marker. However, the effect of C. pneumoniae
      on lipid metabolism in vascular endothelial cells is yet to be elucidated. The
      aim of the present study was to investigate the effects of C. pneumoniae on lipid
      metabolism in human umbilical vein endothelial cells (HUVECs). In the present
      study, LDL oxidation was found to be significantly induced in the supernatant,
      but not the cell lysates, of C. pneumoniae-infected HUVECs. Furthermore, C.
      pneumoniae infection was observed to increase the levels of total cholesterol and
      cholesteryl esters in LDL-treated HUVECs. In addition, C. pneumoniae was found to
      upregulate the expression of scavenger receptor A, cluster of differentiation 36
      and acyl-coenzyme A: cholesterol acyltransferase 1 mRNA and protein. C.
      pneumoniae was also observed to downregulate the mRNA and protein expression of
      ATP binding cassette transporter (ABC) A1 and ABCGl in LDL-treated HUVECs. These
      results show that C. pneumoniae disrupts lipid metabolism in HUVECs. 

PMID- 24898284
TI  - The PH gene determines fruit acidity and contributes to the evolution of sweet
      melons.
AB  - Taste has been the subject of human selection in the evolution of agricultural
      crops, and acidity is one of the three major components of fleshy fruit taste,
      together with sugars and volatile flavour compounds. We identify a family of
      plant-specific genes with a major effect on fruit acidity by map-based cloning of
      C. melo PH gene (CmPH) from melon, Cucumis melo taking advantage of the novel
      natural genetic variation for both high and low fruit acidity in this species.
      Functional silencing of orthologous PH genes in two distantly related plant
      families, cucumber and tomato, produced low-acid, bland tasting fruit, showing
      that PH genes control fruit acidity across plant families. A four amino-acid
      duplication in CmPH distinguishes between primitive acidic varieties and modern
      dessert melons. This fortuitous mutation served as a preadaptive antecedent to
      the development of sweet melon cultigens in Central Asia over 1,000 years ago. 

PMID- 24898285
TI  - Pathologic assessment of response to chemotherapy in colorectal cancer liver
      metastases after hepatic resection: which method to use?
AB  - BACKGROUND: Patients with metastatic colorectal cancer receive chemotherapy prior
      liver resection more and more frequently. Histopathologic assessment methods of
      the resected specimen could evaluate the response to chemotherapy. In this study
      it is analyzed if these histopathologic changes are specific to preoperative
      chemotherapy and if these methods have correlation with survival. METHODS: Sixty
      three patients with available pathology slides, resected for colorectal cancer
      liver metastases were enrolled in this study. 46 patients (73%) received
      neoadjuvant chemotherapy. Five pathological evaluation methods were compared
      according to the literature: [1] residual tumor cell ratio, [2] tumor regression
      grade (TRG) scoring system, [3] modified tumor regression grade (mTRG) scoring
      system with the type of necrosis, [4] pattern of tumor regression and [5] the
      tumor thickness at the tumor-normal interface (TNI). RESULTS: Analyzing the
      pathological methods between the chemotherapy (CTX) and the non-chemotherapy
      group (NC), we found that that four evaluation methods showed significant and one
      showed strong correlation with the use of chemotherapy. (Residual tumor cell
      ratio: p = 0.08; TRG: p <0.01; mTRG: p = 0.03; pattern of tumor regression: p
      <0.01; TNI: p = 0.02). In the chemotherapy group none of the analyzed
      pathological methods showed significant correlation with progression free
      survival (PFS) or with overall survival (OS). Residual tumor cell ratio, TRG and
      the pattern of tumor cells showed positive but not significant correlation with
      OS and PFS and a slight difference in the group of patients with TNI <2 mm could
      be documented. CONCLUSIONS: Tumor regression grade (TRG) and tumor thickness at
      the tumor-normal interface (TNI) were the most useful methods for pathological
      response evaluation and these methods had some correlation with survival.
      According to these data, authors concluded, that a reproducible and well defined
      scoring system, based on different histopathological evaluation methods should be
      developed to predict more accurately the effect of neoadjuvant chemotherapy in
      CRCLM patients.

PMID- 24898286
TI  - Frameshift mutations of cadherin genes DCHS2, CDH10 and CDH24 genes in gastric
      and colorectal cancers with high microsatellite instability.
AB  - Cadherins (CDHs) are important in maintenance of cell adhesion and polarity,
      alterations of which contribute to tumorigenesis. Alterations of E-cadherin, a
      prototype CDH, have been reported in many cancers. However, alterations of
      unconventional CDHs, including CDH10, CDH24 and DCHS2 are largely unknown in
      cancers. Aim of this study was to explore whether CDH10, CDH24 and DCHS2 genes
      are mutated in gastric (GC) and colorectal cancers (CRC). In a public database,
      we found that CDH10, CDH24 and DCHS2 genes had mononucleotide repeats in the
      coding sequences that might be mutation targets in the cancers with
      microsatellite instability (MSI). We analyzed the mutations in 89 GC and 131 CRC
      (high MSI (MSI-H) or stable MSI/low MSI (MSS/MSI-L)) by single-strand
      conformation polymorphism analysis and DNA sequencing. We found six DCHS2, one
      CDH10 and one CDH24 frameshift mutations in them. All of the mutations were
      detected in cancers with MSI-H and there was a statistical difference in the
      frameshift mutation frequencies between the cancers with MSI-H (8/105) and
      MSS/MSI-L (0/115). The DCHS2 frameshift mutations were found in 8.8% and 4.2% of
      GC and CRC with MSI-H respectively. Our results show that unconventional CDH10,
      CDH24 and DCHS2 genes harbored frameshift mutations. These mutations might
      inactivate the cell adhesion-related functions and could be a feature of GC and
      CRC with MSI-H.

PMID- 24898287
TI  - [Dizziness and syncope : clinical case examples].
AB  - Syncope is defined as a transient, self-limiting loss of consciousness and
      postural tone due to transient global cerebral hypoperfusion. After syncope the
      following questions have to be answered: was it a syncopal episode, has the
      etiological diagnosis been determined, are there data suggestive of a high risk
      of cardiovascular events or death and what are the therapeutic options?
      Therefore, a standardized diagnostic work-up is necessary. This diagnostic work
      up with differential diagnostic considerations is given for three clinical cases:
      a 52-year-old man experienced syncope while driving a car and on the morning of
      the same day syncope had previously occurred while in a standing position. The
      initial cardiological and neurological evaluation revealed no pathological
      findings but after implantation of a loop recorder a further syncope with a sinus
      arrest of 17 s occurred 1 year later. The patient received a single chamber
      pacemaker. The second case is a 79-year-old female with Parkinson's disease for
      many years and a primary autonomic dysfunction leading to dizziness and syncope
      due to pronounced blood pressure fluctuations with hypertensive and hypotensive
      phases. The last patient is a 22-year-old female with postural orthostatic
      tachycardia syndrome and recurrent syncope. The diagnostic evaluation and
      treatment proved to be difficult. 

PMID- 24898288
TI  - Comparative analysis of GATA3 mutation profiles between Asian and Western
      patients with breast cancer. Is there really a difference?

PMID- 24898289
TI  - The binding force of the staphylococcal adhesin SdrG is remarkably strong.
AB  - SdrG is a cell surface adhesin from Staphylococcus epidermidis which binds to the
      blood plasma protein fibrinogen (Fg). Ligand binding follows a 'dock, lock and
      latch' model involving dynamic conformational changes of the adhesin that result
      in a greatly stabilized adhesin-ligand complex. To date, the force and dynamics
      of this multistep interaction are poorly understood. Here we use atomic force
      microscopy (AFM) to unravel the binding strength and cell surface localization of
      SdrG at molecular resolution. Single-cell force spectroscopy shows that SdrG
      mediates time-dependent attachment to Fg-coated surfaces. Single-molecule force
      spectroscopy with Fg-coated AFM tips demonstrates that the adhesin forms
      nanoscale domains on the cell surface, which we believe contribute to strengthen
      cell adhesion. Notably, we find that the rupture force of single SdrG-Fg bonds is
      very large, ~ 2 nN, equivalent to the strength of a covalent bond, and shows a
      low dissociation rate, suggesting that the bond is very stable. The strong
      binding force, slow dissociation and clustering of SdrG provide a molecular
      foundation for the ability of S. epidermidis to colonize implanted biomaterials
      and to withstand physiological shear forces. 

PMID- 24898290
TI  - Tuning the halogen/hydrogen bond competition: a spectroscopic and conceptual DFT
      study of some model complexes involving CHF2I.
AB  - Insight into the key factors driving the competition of halogen and hydrogen
      bonds is obtained by studying the affinity of the Lewis bases trimethylamine
      (TMA), dimethyl ether (DME), and methyl fluoride (MF) towards difluoroiodomethane
      (CHF(2) I). Analysis of the infrared and Raman spectra of solutions in liquid
      krypton containing mixtures of TMA and CHF(2) I and of DME and CHF(2) I reveals
      that for these Lewis bases hydrogen and halogen-bonded complexes appear
      simultaneously. In contrast, only a hydrogen-bonded complex is formed for the
      mixtures of CHF(2) I and MF. The complexation enthalpies for the C-H???Y hydrogen
      bonded complexes with TMA, DME, and MF are determined to be -14.7(2), -10.5(5)
      and -5.1(6) kJ mol(-1), respectively. The values for the C-I???Y halogen-bonded
      isomers are -19.0(3) kJ mol(-1) for TMA and -9.9(8) kJ mol(-1) for DME.
      Generalization of the observed trends suggests that, at least for the bases
      studied here, softer Lewis bases such as TMA favor halogen bonding, whereas
      harder bases such as MF show a substantial preference for hydrogen bonding.

PMID- 24898291
TI  - Anomalous left coronary artery connected to the pulmonary artery associated with
      other cardiac defects: a difficult joint diagnosis.
AB  - Anomalous left coronary artery connected to the pulmonary artery (ALCAPA) can be
      associated rarely with other congenital heart defects. The preoperative joint
      diagnosis is challenging. From 1987 to 2012, a retrospective bicentric assessment
      of 12 patients with ALCAPA related to other cardiac defects focused on the
      associated heart defect, the moment of complete diagnosis related to surgery, and
      outcome. Coarctation was the most frequently associated heart defect (n = 5)
      followed by tetralogy of Fallot with or without pulmonary atresia (n = 3). The
      study group comprised one case of hypoplastic left heart syndrome, one right
      aortic arch, one congenital mitral malformation, and one infant with divided left
      atrium and anomalous pulmonary venous return. Only four patients had a complete
      diagnosis of both the cardiac defect and the coronary abnormality before surgery.
      In two cases, the coronary anomaly was discovered during surgery performed for
      another cardiac defect and treated at the same time. The diagnosis of the six
      remaining patients was determined after cardiac repair. Of the 12 patients, 7 (58
      %) died after surgery. Half of these patients died within the first 30 days after
      repair. At this writing, the remaining patients are in good health after a median
      follow-up period of 5.4 years (range, 2.1-8.5 years). This study confirmed that
      ALCAPA associated with other cardiac defects often is misdiagnosed before
      surgery, mostly due to specific hemodynamics masking myocardial ischemia
      preoperatively. Survival was compromised due to the unrecognized diagnosis of an
      associated coronary abnormality but also because of midterm complications related
      to the other cardiac defects.

PMID- 24898292
TI  - Blood pressure screening for critical congenital heart disease in neonates.
AB  - Pulse oximetry (POx) screening for critical congenital heart disease (CCHD) in
      neonates is less effective in identifying aortic arch obstruction than in
      detecting other forms of CCHD. This study was performed to assess the use of
      neonatal blood pressure (BP) screening to detect CCHD. A retrospective review of
      BP and POx measurements performed at the age of 24 h or before discharge in
      asymptomatic term neonates was undertaken. The charts of infants readmitted
      younger than 30 days with a diagnosis of CCHD also were reviewed to identify
      infants with a missed diagnosis. The screening process was completed for 10,012
      of 10,436 infants. Because of an abnormal initial result, 164 neonates required a
      repeat screening (139 due to abnormal BP). A total of 12 infants failed the BP
      screening component, and 1 infant failed both the BP and Pox components. The
      average final right arm-to-leg BP gradient was 25 mmHg in these 13 babies. For
      nine infants, CCHD was excluded by echocardiography. Three patients were normal
      at their 1-year well-child exam, and one patient was lost to follow-up
      evaluation. No infants were identified who had been discharged home with a missed
      diagnosis of CCHD. Neonatal BP screening to detect CCHD was responsible for more
      inappropriately performed screenings, repeated screenings, and screening failures
      than the POx component of the screening protocol and had a highest possible
      positive predictive value of 1 in 13. These data suggests that BP screening at
      the time of routine newborn hospital discharge is of limited value in the
      detection of unrecognized CCHD.

PMID- 24898293
TI  - Facile LC-UV methods for simultaneous monitoring of ciprofloxacin and
      rosuvastatin in API, formulations and human serum.
AB  - An efficient, selective and cost-effective liquid chromatographic assay was
      developed and validated for the simultaneous quantification of ciprofloxacin and
      rosuvastatin in Active Pharmaceutical Ingredients (API), pharmaceutical
      formulations and in human serum. The chromatographic system consisted of mobile
      phase methanol-water, 90:10 v/v at pH 3.0 adjusted with o-phosphoric acid, pumped
      at 1.0 mL/min through a prepacked Purospher Star C18 (5 um, 25 * 0.46 cm) column
      and effluent was monitored at the isosbestic point (255 nm) as well as at the
      lambdamax of individual drugs (243 and 271 nm). The method was validated over a
      linear concentration range of 0.25-15 ug/mL for ciprofloxacin and 0.33-20 ug/mL
      for rosuvastatin (r(2)  >= 0.999). The ranges of reliable response (limits of
      detection and quantitation) for ciprofloxacin were 3-15 and 9-45 ng/mL and 17-29
      and 52-88 ng/mL, respectively, for rosuvastatin in all API, pharmaceutical
      formulations and human serum. Analytical recovery from human serum was >98% and
      relative standard deviation (RSD) was <2. The accuracies were 97.13-102.55 and
      97.41-101.31% and precisions in RSD were 0.04-1.90 and 0.02-1.23% for
      ciprofloxacin and rosuvastatin, respectively. No matrix interferences, ion
      suppression/enhancement and carry-over were detected. The total assay run time
      was less than 5 min. In another study, for optimum performance the detector was
      programmed for multiwavelength scanning at the absorption maxima of each
      component. Consequently, the linearity range was improved and limit of detection
      and quantitation values were down to 1-4 and 4-12 ng/mL for ciprofloxacin and 3-5
      and 9-15 ng/mL for rosuvastatin, respectively. The validation parameters fitted
      ICH guidelines through the isosbestic and individual lambdamax approach. The
      small sample volume and simplicity of preparation make this method suitable for
      use in human serum samples, pharmaceutical formulations, quality control, drug
      drug interaction studies, clinical laboratories, drug research centers and
      forensic medical centers.

PMID- 24898295
TI  - Influence of aqueous environment on agglomeration and dissolution of thiol
      functionalised mesoporous silica-coated magnetite nanoparticles.
AB  - The purpose of the present research work is to investigate the stability and
      dissolution of magnetite (Fe3O4) nanoparticles (NPs) and thiol-functionalised
      mesoporous silica-coated magnetite NPs (TF-SCMNPs). The state of NPs in an
      aqueous environment was investigated under different pH conditions. Changes in
      the NPs' mean diameter due to aggregation were measured over a specific time. The
      effects of contact time and pH on the dissolution of NPs were also investigated.
      In order to avoid possible aggregation, Fe3O4 NPs were coated with silica and
      functionalised further with thiol organic groups. These methods imparted
      excellent stability to magnetite NPs in an aqueous medium over a wide range of pH
      values with reasonable hydrodynamic size. The organic group bound magnetite NPs
      allowed these particles to circulate over a long time in the aqueous system, and
      particle aggregation and sedimentation did not occur. The trend of decreasing
      zeta potential was observed after grafting thiol onto the surface of the SCMNPs.
      The results also revealed that silica exhibited a noteworthy efficient in
      eliminating the pH dependence and enhancing the NP stability of SCMNPs and SH
      SCMNPs in aqueous medium. On the other hand, the dissolution of Fe3O4 NPs was
      found to be detrimental at pH 2.0 and 4.0 or had a long contact time.

PMID- 24898294
TI  - Behavior of sartans (antihypertensive drugs) in wastewater treatment plants,
      their occurrence and risk for the aquatic environment.
AB  - Pharmaceuticals and other anthropogenic trace contaminants reach wastewaters and
      are often not satisfactorily eliminated in sewage treatment plants. These
      contaminants and/or their degradation products may reach surface waters, thus
      influencing aquatic life. In this study, the behavior of five different
      antihypertonic pharmaceuticals from the sartan group (candesartan, eprosartan,
      irbesartan, olmesartan and valsartan) is investigated in lab-scale sewage plants.
      The elimination of the substances with related structures varied broadly from 17
      % for olmesartan up to 96 % for valsartan. Monitoring data for these drugs in
      wastewater effluents of six different sewage treatment plants (STPs) in Bavaria,
      and at eight rivers, showed median concentrations for, e.g. valsartan of 1.1 and
      0.13 MUg L(-1), respectively. Predicted environmental concentrations (PEC) were
      calculated and are mostly consistent with the measured environmental
      concentrations (MEC). The selected sartans and the mixture of the five sartans
      showed no ecotoxic effects on aquatic organisms in relevant concentrations.
      Nevertheless, the occurrence of pharmaceuticals in the environment should be
      reduced to minimize the risk of their distribution in surface waters, ground
      waters and bank filtrates used for drinking water.

PMID- 24898296
TI  - The relationship between air pollution, fossil fuel energy consumption, and water
      resources in the panel of selected Asia-Pacific countries.
AB  - The objective of the study is to examine the relationship between air pollution,
      fossil fuel energy consumption, water resources, and natural resource rents in
      the panel of selected Asia-Pacific countries, over a period of 1975-2012. The
      study includes number of variables in the model for robust analysis. The results
      of cross-sectional analysis show that there is a significant relationship between
      air pollution, energy consumption, and water productivity in the individual
      countries of Asia-Pacific. However, the results of each country vary according to
      the time invariant shocks. For this purpose, the study employed the panel least
      square technique which includes the panel least square regression, panel fixed
      effect regression, and panel two-stage least square regression. In general, all
      the panel tests indicate that there is a significant and positive relationship
      between air pollution, energy consumption, and water resources in the region. The
      fossil fuel energy consumption has a major dominating impact on the changes in
      the air pollution in the region. 

PMID- 24898298
TI  - Neural stem cells differentiated from iPS cells spontaneously regain
      pluripotency.
AB  - Differentiated somatic cells can be reprogrammed into pluripotent stem cells by
      transduction of exogenous reprogramming factors. After induced pluripotent stem
      (iPS) cells are established, exogenous genes are silenced. In the pluripotent
      state, retroviral genes integrated in the host genome are kept inactive through
      epigenetic transcriptional regulation. In this study, we tried to determine
      whether exogenous genes remain silenced or are reactivated upon loss of
      pluripotency or on differentiation using an in vitro system. We induced
      differentiation of iPS cells into neural stem cells (NSCs) in vitro; the NSCs
      appeared morphologically indistinguishable from brain-derived NSCs and stained
      positive for the NSC markers Nestin and Sox2. These iPS cell-derived NSCs (iPS
      NSCs) were also capable of differentiating into all three neural subtypes.
      Interestingly, iPS-NSCs spontaneously formed aggregates on long-term culture and
      showed reactivation of the Oct4-GFP marker, which was followed by the formation
      of embryonic stem cell-like colonies. The spontaneously reverted green
      fluorescent protein (GFP)-positive (iPS-NSC-GFP(+) ) cells expressed high levels
      of pluripotency markers (Oct4 and Nanog) and formed germline chimeras, indicating
      that iPS-NSC-GFP(+) cells had the same pluripotency as the original iPS cells.
      The reactivation of silenced exogenous genes was tightly correlated with the
      downregulation of DNA methyltransferases (Dnmts) during differentiation of iPS
      cells. This phenomenon was not observed in doxycycline-inducible iPS cells, where
      the reactivation of exogenous genes could be induced only by doxycycline
      treatment. These results indicate that pluripotency can be regained through
      reactivation of exogenous genes, which is associated with dynamic change of Dnmt
      levels during differentiation of iPS cells.

PMID- 24898297
TI  - The mitochondrial unfolded protein response in mammalian physiology.
AB  - Mitochondria, the main site of cellular energy harvesting, are derived from
      proteobacteria that evolved within our cells in endosymbiosis. Mitochondria
      retained vestiges of their proteobacterial genome, the circular mitochondrial
      DNA, which encodes 13 subunits of the oxidative phosphorylation multiprotein
      complexes in the electron transport chain (ETC), while the remaining ~80 ETC
      components are encoded in the nuclear DNA (nDNA). A further ~1,400 proteins,
      which are essential for mitochondrial function are also encoded in nDNA. Thus, a
      majority of mitochondrial proteins are translated in the cytoplasm, then
      imported, processed, and assembled in the mitochondria. An intricate protein
      quality control (PQC) network, constituted of chaperones and proteases that
      refold or degrade defective proteins, maintains mitochondrial proteostasis and
      ensures the cell and organism health. The mitochondrial unfolded protein response
      is a relatively recently discovered PQC pathway, which senses the proteostatic
      disturbances specifically in the mitochondria and resolves the stress by
      retrograde signaling to the nucleus and consequent transcriptional activation of
      protective genes. This PQC system does not only transiently resolve the local
      stress but also can have long-lasting effects on whole body metabolism, fitness,
      and longevity. A delicate tuning of its activation levels might constitute a
      treatment of various diseases, such as metabolic diseases, cancer, and
      neurodegenerative disorders. 

PMID- 24898299
TI  - Synergism between circulating tumor necrosis factor receptor 2 and HbA(1c) in
      determining renal decline during 5-18 years of follow-up in patients with type 1
      diabetes and proteinuria.
AB  - OBJECTIVE: We studied the serum concentration of tumor necrosis factor receptor 2
      (TNFR2) and the rate of renal decline, a measure of the intensity of the disease
      process leading to end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: A
      cohort of 349 type 1 diabetic patients with proteinuria was followed for 5-18
      years. Serum TNFR2, glycated hemoglobin A1c (HbA1c), and other characteristics
      were measured at enrollment. We used a novel analytic approach, a joint
      longitudinal-survival model, fitted to serial estimates of glomerular filtration
      rate (eGFR) based on serum creatinine (median seven per patient) and time to
      onset of ESRD (112 patients) to estimate the rate of renal decline (eGFR loss).
      RESULTS: At enrollment, all patients had chronic kidney disease stage 1-3. The
      mean (+/-SD) rate of eGFR loss during 5-18 years of follow-up was -5.2 (+/-4.9)
      mL/min/1.73 m(2)/year. Serum TNFR2 was the strongest determinant of renal decline
      and ESRD risk (C-index 0.79). The rate of eGFR loss became steeper with rising
      concentration of TNFR2, and elevated HbA1c augmented the strength of this
      association (P = 0.030 for interaction). In patients with HbA1c >=10.1% (87
      mmol/mol), the difference in the rate of eGFR loss between the first and fourth
      quartiles of TNFR2 was 5.4 mL/min/1.73 m(2)/year, whereas it was only 1.9 in
      those with HbA1c <7.9% (63 mmol/mol). CONCLUSIONS: Circulating TNFR2 is a major
      determinant of renal decline in patients with type 1 diabetes and proteinuria.
      Elevated HbA1c magnifies its effect. Although the mechanisms of this synergism
      are unknown, our findings allow us to stratify patients according to risk of
      ESRD.

PMID- 24898300
TI  - Advancing basal insulin replacement in type 2 diabetes inadequately controlled
      with insulin glargine plus oral agents: a comparison of adding albiglutide, a
      weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro.
AB  - OBJECTIVE: GLP-1 receptor agonists may provide an alternative to prandial insulin
      for advancing basal insulin therapy. Harmony 6 was a randomized, open-label,
      active-controlled trial testing once-weekly albiglutide vs. thrice-daily prandial
      insulin lispro as an add-on to titrated once-daily insulin glargine. RESEARCH
      DESIGN AND METHODS: Patients taking basal insulin (with or without oral agents)
      with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period,
      followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently
      uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281)
      while continuing metformin and/or pioglitazone. Glargine was titrated to fasting
      plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose
      monitoring. The primary end point was the difference in the HbA1c change from
      baseline at week 26. RESULTS: At week 26, HbA1c decreased from baseline by -0.82
      +/- SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 +/- 0.06% (7.2 mmol/mol)
      with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P
      < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased
      with albiglutide but increased with lispro (-0.73 +/- 0.19 kg vs. +0.81 +/- 0.19
      kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44
      to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe
      hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs.
      29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site
      reactions (9.5% vs. 5.3%). CONCLUSIONS: Weekly albiglutide is a simpler
      therapeutic option than thrice-daily lispro for advancing basal insulin glargine
      therapy, resulting in comparable HbA1c reduction with weight loss and lower
      hypoglycemia risk.

PMID- 24898301
TI  - Individual mindfulness-based cognitive therapy and cognitive behavior therapy for
      treating depressive symptoms in patients with diabetes: results of a randomized
      controlled trial.
AB  - OBJECTIVE: Depression is a common comorbidity of diabetes, undesirably affecting
      patients' physical and mental functioning. Psychological interventions are
      effective treatments for depression in the general population as well as in
      patients with a chronic disease. The aim of this study was to assess the efficacy
      of individual mindfulness-based cognitive therapy (MBCT) and individual cognitive
      behavior therapy (CBT) in comparison with a waiting-list control condition for
      treating depressive symptoms in adults with type 1 or type 2 diabetes. RESEARCH
      DESIGN AND METHODS: In this randomized controlled trial, 94 outpatients with
      diabetes and comorbid depressive symptoms (i.e., Beck Depression Inventory-II
      [BDI-II] >=14) were randomized to MBCT (n = 31), CBT (n = 32), or waiting list (n
      = 31). All participants completed written questionnaires and interviews at pre-
      and postmeasurement (3 months later). Primary outcome measure was severity of
      depressive symptoms (BDI-II and Toronto Hamilton Depression Rating Scale).
      Anxiety (Generalized Anxiety Disorder 7), well-being (Well-Being Index), diabetes
      related distress (Problem Areas In Diabetes), and HbA1c levels were assessed as
      secondary outcomes. RESULTS: Results showed that participants receiving MBCT and
      CBT reported significantly greater reductions in depressive symptoms compared
      with patients in the waiting-list control condition (respectively, P = 0.004 and
      P < 0.001; d = 0.80 and 1.00; clinically relevant improvement 26% and 29% vs.
      4%). Both interventions also had significant positive effects on anxiety, well
      being, and diabetes-related distress. No significant effect was found on HbA1c
      values. CONCLUSIONS: Both individual MBCT and CBT are effective in improving a
      range of psychological symptoms in individuals with type 1 and type 2 diabetes.

PMID- 24898302
TI  - Brachial-ankle pulse wave velocity predicts all-cause mortality and
      cardiovascular events in patients with diabetes: the Kyushu Prevention Study of
      Atherosclerosis.
AB  - OBJECTIVE: Whether brachial-ankle pulse wave velocity (baPWV), a noninvasive
      marker for arterial stiffness, is a useful predictive maker for cardiovascular
      events in subjects with diabetes is not established. In the present cohort study,
      we evaluated the benefit of baPWV for the prediction of cardiovascular morbidity
      and mortality in subjects with diabetes. RESEARCH DESIGN AND METHODS: A total of
      4,272 outpatients with diabetes were enrolled in the Kyushu Prevention Study of
      Atherosclerosis. Of these, 3,628 subjects, excluding those with an ankle-brachial
      index of <0.9, were prospectively followed for 3.2 +/- 2.2 years. The baPWV at
      baseline was classified by recursive partitioning (RP) for each end point. We
      plotted the Kaplan-Meier curves for high- and low-baPWV groups, which were
      designated based on the cutoff points, and calculated Cox proportional hazards
      models. RESULTS: The elevation of baPWV quartiles was significantly correlated to
      the incidence of coronary artery events, cerebrovascular events, and all-cause
      mortality. RP revealed baPWVs of 14 and 24 m/s as statistically adequate cutoff
      points for cardiovascular events and mortality, respectively. High-baPWV classes
      showed significantly low event-free ratios in Kaplan-Meier curves for all end
      points and remained independent risks for all-cause mortality and cerebrovascular
      events, but not for coronary artery events after adjustments for age, sex, BMI,
      hypertension, hyperlipidemia, smoking, and hemoglobin A1c by Cox proportional
      hazards models. CONCLUSIONS: This large-scale cohort study provided evidence that
      high baPWV is a useful independent predictor of mortality and cardiovascular
      morbidity in subjects with diabetes.

PMID- 24898303
TI  - Metformin does not affect cancer risk: a cohort study in the U.K. Clinical
      Practice Research Datalink analyzed like an intention-to-treat trial.
AB  - OBJECTIVE: Meta-analyses of epidemiologic studies have suggested that metformin
      may reduce cancer incidence, but randomized controlled trials did not support
      this hypothesis. RESEARCH DESIGN AND METHODS: A retrospective cohort study,
      Clinical Practice Research Datalink, was designed to investigate the association
      between use of metformin compared with other antidiabetes medications and cancer
      risk by emulating an intention-to-treat analysis as in a trial. A total of 95,820
      participants with type 2 diabetes who started taking metformin and other oral
      antidiabetes medications within 12 months of their diagnosis (initiators) were
      followed up for first incident cancer diagnosis without regard to any subsequent
      changes in pharmacotherapy. Cox proportional hazards models were used to estimate
      multivariable-adjusted hazard ratios (HR) and 95% CI. RESULTS: A total of 51,484
      individuals (54%) were metformin initiators and 18,264 (19%) were sulfonylurea
      initiators, and 3,805 first incident cancers were diagnosed during a median
      follow-up time of 5.1 years. Compared with initiators of sulfonylurea, initiators
      of metformin had a similar incidence of total cancer (HR 0.96; 95% CI 0.89-1.04)
      and colorectal (HR 0.92; 95% CI 0.76-1.13), prostate (HR 1.02; 95% CI 0.83-1.25),
      lung (HR 0.85; 95% CI 0.68-1.07), or postmenopausal breast (HR 1.03; 95% CI 0.82
      1.31) cancer or any other cancer. CONCLUSIONS: In this large study, individuals
      with diabetes who used metformin had a similar risk of developing cancer compared
      with those who used sulfonylureas.

PMID- 24898304
TI  - HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled
      trial assessing the efficacy and safety of albiglutide compared with placebo,
      sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin.
AB  - OBJECTIVE: To compare the efficacy and safety of weekly albiglutide with daily
      sitagliptin, daily glimepiride, and placebo. RESEARCH DESIGN AND METHODS:
      Patients with type 2 diabetes receiving metformin were randomized to albiglutide
      (30 mg), sitagliptin (100 mg), glimepiride (2 mg), or placebo. Blinded dose
      titration for albiglutide (to 50 mg) and glimepiride (to 4 mg) was based on
      predefined hyperglycemia criteria. The primary end point was change in HbA1c from
      baseline at week 104. Secondary end points included fasting plasma glucose (FPG),
      weight, and time to hyperglycemic rescue. RESULTS: Baseline characteristics were
      similar among the albiglutide (n = 302), glimepiride (n = 307), sitagliptin (n =
      302), and placebo (n = 101) groups. Baseline HbA1c was 8.1% (65.0 mmol/mol); mean
      age was 54.5 years. The mean doses for albiglutide and glimepiride at week 104
      were 40.5 and 3.1 mg, respectively. At week 104, albiglutide significantly
      reduced HbA1c compared with placebo (-0.9% [-9.8 mmol/mol]; P < 0.0001),
      sitagliptin (-0.4% [-4.4 mmol/mol]; P = 0.0001), and glimepiride (-0.3% [-3.3
      mmol/mol]; P = 0.0033). Outcomes for FPG and HbA1c were similar. Weight change
      from baseline for each were as follows: albiglutide -1.21 kg (95% CI -1.68 to 
      0.74), placebo -1.00 kg (95% CI -1.81 to -0.20), sitagliptin -0.86 kg (95% CI 
      1.32 to -0.39), glimepiride 1.17 kg (95% CI 0.70-1.63). The difference between
      albiglutide and glimepiride was statistically significant (P < 0.0001).
      Hyperglycemic rescue rate at week 104 was 25.8% for albiglutide compared with
      59.2% (P < 0.0001), 36.4% (P = 0.0118), and 32.7% (P = 0.1504) for placebo,
      sitagliptin, and glimepiride, respectively. Rates of serious adverse events in
      the albiglutide group were similar to comparison groups. Diarrhea (albiglutide
      12.9%, other groups 8.6-10.9%) and nausea (albiglutide 10.3%, other groups 6.2
      10.9%) were generally the most frequently reported gastrointestinal events.
      CONCLUSIONS: Added to metformin, albiglutide was well tolerated; produced
      superior reductions in HbA1c and FPG at week 104 compared with placebo,
      sitagliptin, and glimepiride; and resulted in weight loss compared with
      glimepiride.

PMID- 24898305
TI  - Phase I clinical and pharmacokinetic study of ombrabulin (AVE8062) combined with
      cisplatin/docetaxel or carboplatin/paclitaxel in patients with advanced solid
      tumors.
AB  - PURPOSE: Preclinical evidence supports synergy between the vascular disrupting
      agent ombrabulin and various chemotherapy agents. Ombrabulin was combined with
      two standard taxane/platinum doublets in a phase I study to determine the
      recommended combination doses. METHODS: Ombrabulin (30-min infusion, day 1 every
      3 weeks) was escalated from 15.5 to 35 mg/m(2) with two chemotherapy doublets;
      OCD, 75 mg/m(2) cisplatin (C), day 1 (cohort 1) or day 2 (cohort 2) with 60/75
      mg/m(2) docetaxel (D), day 2; and OCP, AUC5/6 carboplatin (C) and paclitaxel (P)
      175 mg/m(2) (cohort 3) or 200 mg/m(2) (cohort 4), day 2. Safety,
      pharmacokinetics, and tumor response were evaluated. RESULTS: Sixty-nine patients
      were treated (32 OCD, 37 OCP). Four had DLTs in cycle 1, two in cohort 1 (grade 4
      febrile neutropenia, grade 4 pulmonary embolism) and one each in cohorts 2 (grade
      3 ALT elevation) and 4 (grade 3 peripheral ischemia). Ombrabulin escalation in
      cohorts 2, 3 and 4 was halted at the highest planned dose (35 mg/m(2)). Asthenia,
      nausea, paresthesia, alopecia, vomiting, and stomatitis were common, as was grade
      3-4 neutropenia. Ombrabulin clearance was high with a short terminal half-life
      and a medium volume of distribution. Pharmacokinetic analysis showed no
      clinically relevant drug interactions between the taxane-platinum doublet and
      ombrabulin or its active metabolite RPR258063, however docetaxel and carboplatin
      pharmacokinetics were slightly altered. One complete and 15 partial responses (10
      OCD, 5 OCP; median duration 5.5 and 4.4 months, respectively) were reported.
      CONCLUSIONS: The addition of ombrabulin to standard doses of cisplatin/docetaxel
      or carboplatin/paclitaxel proved feasible with manageable overlapping toxicities
      but appears to have limited impact on the efficacy of these doublets. Recommended
      combination doses are 35 mg/m(2) ombrabulin with 75 mg/m(2) cisplatin/75 mg/m(2)
      docetaxel or 200 mg/m(2) paclitaxel/AUC6 carboplatin, every 3 weeks.

PMID- 24898308
TI  - Endovascular management of proximal lower limb deep venous thrombosis - A
      prospective study with six-month follow-up.
AB  - BACKGROUND: Catheter-directed thrombolysis with assisted mechanical thrombolysis
      is the standard of medical care for proximal deep vein thrombosis. We studied the
      immediate and intermediate (six months) safety and effectiveness of catheter
      directed thrombolysis in patients with proximal lower limb deep vein thrombosis.
      METHODOLOGY: Thirty consecutive patients aged between 20 and 70 years with
      proximal lower limb deep vein thrombosis formed the study group. Catheter
      directed thrombolysis was done with streptokinase infuse through a catheter kept
      in the ipsilateral popliteal vein. Unfractionated heparin was given along with
      streptokinase. Mechanical thromboaspiration using guiding catheter was performed
      in addition to thrombolytic therapy. After six months, post-thrombotic syndrome
      and deep venous patency were assessed by using Villalta scale and duplex
      ultrasound, respectively. RESULTS: Thirty patients with proximal lower limb deep
      vein thrombosis were treated with catheter-directed thrombolysis. Mean age of the
      study patients was 41.7 +/- 15 years. Mean duration of illness was 13.3 +/- 12
      days. The mean duration of thrombolysis was 4.5 +/- 1.3 days. Grade III
      (complete) lysis was achieved in 10 (33%) and Grade II (50-90%) lysis in 20 (67%)
      of patients. Patients with significant residual lesion in Grade II lysis
      following catheter-directed thrombolysis underwent percutaneous transluminal
      angioplasty alone (12/20) or venous stenting (8/20). All patients improved
      clinically following catheter-directed thrombolysis or assisted catheter-directed
      thrombolysis. Four patients (13%) developed pulmonary embolism during course of
      hospital stay and among them two (6.5%) patients died. Eleven patients (37%) had
      minor bleeding or hematoma at local site, and seven (23%) developed anemia
      requiring blood transfusion and four (13%) patients had thrombocytopenia. After
      six months, iliofemoral patency was found in 20 (72%) and post-thrombotic
      syndrome was seen in six (21%) patients. Two (6.5%) patients died during follow
      up due to nephrotic syndrome and carcinoma breast. CONCLUSION: Catheter-directed
      thrombolysis and conventional manual aspiration thrombectomy are an effective
      treatment for proximal lower extremity deep vein thrombosis with good short and
      intermediate outcome.

PMID- 24898309
TI  - Public and private health service in Norway: a comparison of patient
      characteristics and surgery criteria for patients with nerve root affections due
      to discus herniation.
AB  - PURPOSE: To compare sociodemographic, life style and clinical characteristics in
      patients operated for lumbar disc herniation in public and private clinics in
      Norway, and evaluate whether selection for surgery and surgical treatment were
      different across the two settings. METHODS: A cross-sectional multicenter study
      of patients who underwent elective surgeries for lumbar disc herniation at 41 (31
      public and 10 private) hospitals. Data were included in the Norwegian Registry
      for Spine Surgery. RESULTS: Of the 5,308 elective surgical procedures, 3,628 were
      performed at public hospitals and 1,680 at private clinics. Patients in the
      private clinics were slightly younger, more likely to be man, have higher level
      of education, and more likely to be employed. Disability and retirement pensions
      were more than double in the public as compared to the private clinics. Mean
      duration of sick leave was 24 weeks (SD 36.4) in the public and 15 weeks (20.7)
      in the private clinics. There were minor differences in pain, disability and
      quality-of life, number of verified disc herniations and radiological findings.
      Number of days at hospital, total operation time and proportion of complications
      were significantly higher in the public than in the private clinics. CONCLUSION:
      Patients having elective surgery due to lumbar disc herniation in public and
      private clinics were different with respect to many sociodemographic and life
      style variables. There were minor differences with respect to clinical variables
      and selection of patients for surgery, but substantial differences related to
      aspects of the surgical treatment.

PMID- 24898306
TI  - The impact of dietary isoflavonoids on malignant brain tumors.
AB  - Poor prognosis and limited therapeutic options render malignant brain tumors one
      of the most devastating diseases in clinical medicine. Current treatment
      strategies attempt to expand the therapeutic repertoire through the use of
      multimodal treatment regimens. It is here that dietary fibers have been recently
      recognized as a supportive natural therapy in augmenting the body's response to
      tumor growth. Here, we investigated the impact of isoflavonoids on primary brain
      tumor cells. First, we treated glioma cell lines and primary astrocytes with
      various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent
      manner was measured for biochanin A (BCA), genistein (GST), and
      secoisolariciresinol diglucoside (SDG). Dose-response action for the different
      isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic
      for normal differentiated brain tissues. We further investigated BCA in ex vivo
      and in vivo experimentations. Organotypic brain slice cultures were performed and
      treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in
      tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by
      magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain
      slice cultures (VOGIM) we found that BCA operates antiangiogenic and
      neuroprotective. In vivo MRI scans demonstrated that administered BCA as a
      monotherapy was effective in reducing significantly tumor-induced brain edema and
      showed a trend for prolonged survival. Our results revealed that dietary
      isoflavonoids, in particular BCA, execute toxicity toward glioma cells,
      antiangiogenic, and coevally neuroprotective properties, and therefore augment
      the range of state-of-the-art multimodal treatment approach. 

PMID- 24898310
TI  - Determinants of evolution of endplate and disc degeneration in the lumbar spine:
      a multifactorial perspective.
AB  - PURPOSE: Evolution and progression of disc and endplate bone marrow degeneration
      of the lumbar spine are thought to be multifactorial, yet, their influence and
      interactions are not understood. The aim of this study was to find association of
      potential predictors of evolution of degeneration of the lumbar spine. METHODS:
      Patients (n = 90) who underwent two lumbar magnetic resonance imaging (MRI) exams
      with an interval of at least 4 years and without any spinal surgery were included
      into the longitudinal cohort study with nested case-control analysis. Disc
      degeneration (DD) was scored according to the Pfirrmann classification and
      endplate bone marrow changes (EC) according to Modic in 450 levels on both MRIs.
      Potential variables for degeneration such as age, gender, BMI, scoliosis and
      sagittal parameters were compared between patients with and without evolution or
      progression of degenerative changes in their lumbar spine. A multivariate
      analysis aimed to identify the most important variables for progression of disc
      and endplate degeneration, respectively. RESULTS: While neither age, gender, BMI,
      sacral slope or the presence of scoliosis could be identified as progression
      factor for DD, a higher lordosis was observed in subjects with no progression (49
      degrees  +/- 11 degrees  vs 43 degrees  +/- 12 degrees ; p = 0.017). Progression
      or evolution of EC was only associated with a slightly higher degree of scoliosis
      (10 degrees  +/- 10 degrees  vs 6 degrees  +/- 9 degrees ; p = 0.04) and not to
      any of the other variables. CONCLUSION: While a coronal deformity of the lumbar
      spine seems associated with evolution or progression of EC, a higher lumbar
      lordosis is protective for radiographic progression of DD. This implies that
      scoliotic deformity and lesser lumbar lordosis are associated with higher overall
      degeneration of the lumbar spine.

PMID- 24898311
TI  - Electrophysiologic deterioration in surgery for thoracic disc herniation: impact
      of mean arterial pressures on surgical outcome.
AB  - OBJECTIVE: Severe thoracic disc herniation leads to increased pressure in
      adjacent neural structures, which in turn can require an increase in mean
      arterial pressure (MAP) to maintain adequate spinal cord perfusion. We report a
      case series of three patients with severe thoracic disc herniation that
      experienced deteriorations in motor-evoked potentials (MEPs) and somatosensory
      evoked potentials (SSEPs) following induction of general anesthesia, but prior to
      decompression of the neural elements. METHODS: In-depth chart reviews were
      completed for each patient from their initial presentation to long-term post
      operative course. Careful attention was taken with regards to MAP at induction of
      each operative case. RESULTS: The origin of the decreased signals in all patients
      was thought to relate to inadequate cord perfusion pressures. Two of the patients
      recovered pre-operative neurologic function while the third was left with mild
      post-operative paraparesis. Mean arterial pressures at time of deterioration were
      noted to be 58, 80, and 60 mmHg. These measurements represented MAPs
      approximately 65, 92, and 60 % those of baseline values, respectively.
      CONCLUSION: Based on these experiences, the authors' institution has adopted new
      guidelines in the setting of thoracic disc herniations that includes pre
      operative optimization of volume status, placement of an awake arterial line
      prior to induction of anesthesia, use of MEP and SSEP electrophysiologic
      monitoring, careful selection of anesthetic, and aggressive maintenance of MAPs
      >110 % of preoperative values at all times prior to decompression of the spinal
      cord.

PMID- 24898312
TI  - The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related
      behavior in a rat model of neuropathic pain.
AB  - INTRODUCTION: Some antidepressants are effective for treating neuropathic pain
      independent of any effect on depression. Selective serotonin reuptake inhibitors
      (SSRIs) are one of the potential agents to treat neuropathic pain. The aims of
      this study were to compare the effects of SSRI and non-steroidal anti
      inflammatory drugs (NSAIDs) on pain-related behavior and expression of cytokines
      in a rat model of neuropathic pain. MATERIALS AND METHODS: Spinal surgery was
      performed to apply nucleus pulposus (NP) to the dorsal root ganglion (DRG). NP
      animals were treated with saline (NP + S), meloxicam (NP + M), or low-dose or
      high-dose paroxetine (NP + PL and NP + PH), respectively. Behavioral testing was
      performed to investigate the mechanical withdrawal thresholds. The numbers of TNF
      immunoreactive (IR) neurons in the DRG and of Iba1-IR microglia in the spinal
      cord (SC) were evaluated using immunohistochemistry. Expression of TNF in the DRG
      was examined using Western blots. RESULTS: The thresholds on days 14, 21, and 28
      were higher in the drug-treated animals than in the NP + S group (p < 0.05). The
      number of TNF-IR neurons in DRGs from the NP + M group increased on day 2 and
      decreased on day 7, and TNF expression in DRGs was significantly higher in the NP
      + S group than in the NP + M group on days 7, 14. The number of Iba1-IR microglia
      in the SC was significantly higher in the NP + S group than in the NP + M, NP +
      PL, and NP + PH groups on days 7 and 14. CONCLUSION: An antidepressant might be a
      potential agent to treat lumbar disc herniation as well as NSAIDs.

PMID- 24898313
TI  - Pelvic retroversion is the key protective mechanism of L4-5 degenerative
      spondylolisthesis.
AB  - PURPOSE: To explore the role of spinopelvic sagittal alignment in the
      pathological mechanism of degenerative spondlylolisthesis (DS) development.
      METHOD: A total of 52 asymptomatic volunteers, 32 single segment L4-5 DS and 29
      lumbar spinal stenosis (LSS) without spondylolisthesis patients were enrolled.
      All subjects had standard lumbar spine X-ray films with standard position along
      with lumbar spine magnetic resonance image. Comparative analysis of sagittal
      parameters and disc degeneration grades among asymptomatic volunteers and
      patients with the two disorders were performed. RESULTS: Compared to normal
      population (NP) and LSS, DS showed significantly greater pelvic incidence (PI),
      sacral slope (SS) and lumbar lordosis (LL), while LSS showed significantly
      smaller PT and PT/SS. DS showed significantly greater L5 slope than NP and LSS.
      In both Great-PI group and Small-PI group, all above differences between DS and
      LSS remained. LSS showed significantly higher degenerative grade of each adjacent
      disc than DS. Population with adjacent segment degeneration showed higher
      incidence of pelvic retroversion (PT/SS >=1), and LSS showed greater proportion
      of adjacent segment degeneration than DS. CONCLUSIONS: Lumbar spine morphology of
      great LL determined by great PI is a risk factor of L4-5 DS. L5 slope is a
      parameter that can be used to predict the risk of L4-5 DS. Pelvic retroversion is
      the key protective mechanism from DS. Adjacent segment degeneration is a driving
      factor of pelvic retroversion for compensation of lumbar sagittal malalignment.

PMID- 24898314
TI  - Early life histories of the London poor using delta13C and delta15N stable
      isotope incremental dentine sampling.
AB  - High resolution incremental isotopic analysis of the dentine from early forming
      teeth, especially first molars (M1s), provides a means to assess the effects of
      poor childhood nutrition and healthcare on individuals in an assemblage where
      there are no infants to study. This approach is applied to an 18th and 19th
      century cemetery population associated with St Saviour's Almshouse burial ground
      in Southwark, London, to assess whether, or how, early dietary history, including
      weaning age, influenced health and nutritional status. The results show a general
      pattern in which non-breast milk foods were introduced before or by 6 months of
      age, as indicated by elevated delta(15) N during this period. Almost all
      individuals for which we also have second molar (M2) records, showed lower
      delta(15) N values from a very young age (>1 year) until approximately 8-10
      years, compared to adult values. The overall results show a significant
      difference in delta(1) (3) C (p = 0 to 4sf, F = 17.327) and a weaker statistical
      difference in delta(15) N between males and females (p = 0.019, F = 5.581). One
      possible cause of this is a difference in the diet of males and females early in
      life, or alternatively, a greater susceptibility of males to nutritional
      deprivation compared to females. The latter argument is strengthened by a
      significant difference in the incidence of enamel hypoplasia between the males
      and females, with 7.7% of male teeth showing defects, compared to 3.9% of
      females.

PMID- 24898315
TI  - Mesenchymal stem cell therapy for cardiac repair.
AB  - OPINION STATEMENT: Owing to the prevalence of heart disease and the lack of
      effective long-term solutions for managing cardiac injury, research has turned to
      cell therapy as a potential mechanism for myocardial repair. Mesenchymal stem
      cells (MSC) in particular have become popular because their differentiative
      ability and their angiogenic and immunomodulatory properties make them attractive
      candidates for transplantation. However, there is still debate regarding the
      optimal strategy for the delivery of these cells. Recent clinical studies have
      isolated MSCs from a variety of tissue origins and have also tested the benefits
      of pretreatment with cardiogenic growth factors. Meanwhile, a newer school of
      thought instead supports the utilization of cardiomyocytes generated from MSC
      derived induced pluripotent stem cells. This review will examine the promise of
      MSC therapy, discuss the results of past work, and propose steps that must be
      taken in the future.

PMID- 24898316
TI  - Strategies to reduce bleeding risk in acute coronary syndromes and percutaneous
      coronary intervention: new and emerging pharmacotherapeutic considerations.
AB  - Bleeding is a well-recognized complication among patients who undergo
      percutaneous coronary intervention for acute coronary syndromes. Patients who
      bleed in this setting have higher morbidity, mortality, and resource use. Several
      bleeding avoidance strategies have been identified including the use of certain
      pharmacologic interventions; however, the antithrombotic landscape for this
      patient population is evolving rapidly. Numerous practical issues are related to
      the appropriate selection and dosing of antiplatelets and anticoagulants, as well
      as their combinations, that may have an impact on bleeding. Thus we reviewed the
      recent evidence that describes the use of these agents and provide
      recommendations on the appropriate use of antiplatelets and anticoagulants in the
      context of current practice and guideline recommendations. Opportunities exist to
      reduce bleeding complications through the adoption of bleeding avoidance
      strategies and appropriate use of antiplatelets and anticoagulants. Pharmacist
      expertise is critical in the appropriate selection, dosing, and monitoring of
      these medications to improve patient safety as it relates to bleeding potential.
      Clinical outcomes evaluating combinations of antiplatelets and anticoagulants,
      particularly with novel anticoagulants, are ongoing as are studies that
      incorporate use of genotype and phenotype into antithrombotic decision making. 

PMID- 24898318
TI  - Improving adolescent social competence and behavior: a randomized trial of an 11
      week equine facilitated learning prevention program.
AB  - There is growing evidence that promoting social competence in youth is an
      effective strategy to prevent mental, emotional, and behavioral disorders in
      adulthood. Research suggests that programs delivered in collaboration with
      schools are particularly effective when they target social and emotional skill
      building, utilize an interactive instructional style, provide opportunities for
      youth participation and self-direction, and include explicit attempts to enhance
      youth social competence. A relatively new but popular approach that incorporates
      these characteristics is human animal interaction, which can be implemented in
      educational settings. We report the results from a randomized clinical trial
      examining the effects of an 11-week equine facilitated learning (EFL) program on
      the social competence and behavior of 5th-8th grade children. Children (N = 131)
      were recruited through referral by school counselors and school-based recruitment
      and then screened for low social competence. Researchers randomly assigned
      children to an experimental (n = 53) or waitlisted control group (n = 60).
      Children in the experimental group participated in an 11-week EFL program
      consisting of once-weekly, 90-min sessions of individual and team-focused
      activities, whereas children in the control group served as a wait-listed control
      and participated 16 weeks later. Parents of children in both groups rated child
      social competence at pretest and posttest. Three independent raters observed and
      reported children's positive and negative behavior using a validated checklist
      during each weekly session. Results indicated that program participation had a
      moderate treatment effect (d = .55) on social competence (p = .02) that was
      independent of pretest levels, age, gender, and referral status. Results showed
      that higher levels of program attendance predicted children's trajectories of
      observed positive (beta = .500; p = .003) and negative behavior (beta = -.062; p
      < .001) over the 11-week program.

PMID- 24898319
TI  - No evidence of aquatic priming effects in hyporheic zone microcosms.
AB  - The priming effect refers to quantitative changes in microbial decomposition of
      recalcitrant organic matter upon addition of labile organic matter and is a
      phenomenon that mainly has been reported and debated in soil science. Recently,
      priming effects have been indicated in aquatic ecosystems and have received
      attention due to the potential significance for ecosystem carbon budgets.
      Headwater stream biofilms, which are important degraders of both allochthonous,
      presumably recalcitrant, organic matter and labile autochthonous organic matter,
      may be sites where priming effects are important in aquatic environments. We have
      experimentally tested for priming effects in stream biofilms within microcosms
      mimicking the stream hyporheic zone. A (13)C labeled model allochthonous carbon
      source was used in combination with different carbon sources simulating
      autochthonous inputs. We did not detect changes in respiration, removal or
      incorporation of allochthonous organic matter in response to autochthonous
      treatments, thus not supporting the occurrence of priming effects under the
      experimental conditions. This study is the first to address priming effects in
      the hyporheic zone, and one of very few studies quantitatively assessing aquatic
      priming effects. The results contrast with existing studies, which highlights the
      need for quantitative approaches to determine the importance of priming effects
      in aquatic environments. 

PMID- 24898317
TI  - Dynamic imbalance between cancer cell subpopulations induced by transforming
      growth factor beta (TGF-beta) is associated with a DNA methylome switch.
AB  - BACKGROUND: Distinct subpopulations of neoplastic cells within tumors, including
      hepatocellular carcinoma (HCC), display pronounced ability to initiate new tumors
      and induce metastasis. Recent evidence suggests that signals from transforming
      growth factor beta (TGF-beta) may increase the survival of these so called tumor
      initiating cells leading to poor HCC prognosis. However, how TGF-beta establishes
      and modifies the key features of these cell subpopulations is not fully
      understood. RESULTS: In the present report we describe the differential DNA
      methylome of CD133-negative and CD133-expressing liver cancer cells. Next, we
      show that TGF-beta is able to increase the proportion of CD133+ cells in liver
      cancer cell lines in a way that is stable and persistent across cell division.
      This process is associated with stable genome-wide changes in DNA methylation
      that persist through cell division. Differential methylation in response to TGF
      beta is under-represented at promoter CpG islands and enriched at gene bodies,
      including a locus in the body of the de novo DNA methyl-transferase DNMT3B gene.
      Moreover, phenotypic changes induced by TGF-beta, including the induction of
      CD133, are impaired by siRNA silencing of de novo DNA methyl-transferases.
      CONCLUSIONS: Our study reveals a self-perpetuating crosstalk between TGF-beta
      signaling and the DNA methylation machinery, which can be relevant in the
      establishment of cellular phenotypes. This is the first indication of the ability
      of TGF-beta to induce genome-wide changes in DNA methylation, resulting in a
      stable change in the proportion of liver cancer cell subpopulations.

PMID- 24898320
TI  - Activation of aryl hydrocarbon receptor signaling by extracts of teak and other
      wood dusts.
AB  - Wood dusts, as a group, are categorized as known human carcinogens, but the risks
      of exposure to specific types of wood dusts and the carcinogenic chemicals they
      contain are not well studied. Aryl hydrocarbon receptor (AhR) is a ligand
      activated transcription factor that is linked to the carcinogenic action of
      specific classes of chemicals. Here we examined whether chemicals in various wood
      dusts had the potential to activate AhR signaling as a potential toxic mechanism
      of action. We found that methanol extracts of teak, walnut, mahogany, and poplar
      dusts contained a wide range of AhR ligand activity, whereas extracts of oak,
      pine, and other softwoods did not contain appreciable activity. Teak dust
      extract, being particularly potent, was subjected to chemical analysis. The 2
      methylanthraquinone (2-MAQ) accounted for the AhR ligand activity and was present
      at an average concentration of 0.27 parts per hundred in teak dust. Pure 2-MAQ
      potently induced AhR signaling (EC50 115 nM), confirming that this was the active
      ligand. Aqueous extracts of teak dust made using yeast or mammalian cell culture
      medium also contained robust AhR activity, suggesting the 2-MAQ ligand is soluble
      at bioactive concentrations in physiologically relevant fluids. The high
      concentration and potency of 2-MAQ in teak wood suggest it may mediate toxic
      effects through activation of AhR signaling in exposed wood workers.

PMID- 24898321
TI  - Prediction of polycystic ovarian syndrome based on ultrasound findings and
      clinical parameters.
AB  - OBJECTIVE: To determine the accuracy of sonographic-diagnosed polycystic ovaries
      and clinical parameters in predicting polycystic ovarian syndrome. METHODS:
      Medical records and ultrasounds of 151 women with sonographically diagnosed
      polycystic ovaries were reviewed. Sonographic criteria for polycystic ovaries
      were based on 2003 Rotterdam European Society of Human Reproduction and
      Embryology/American Society for Reproductive Medicine guidelines: at least one
      ovary with 12 or more follicles measuring 2-9 mm and/or increased ovarian volume
      >10 cm(3) . Clinical variables of age, gravidity, ethnicity, body mass index, and
      sonographic indication were collected. One hundred thirty-five patients had final
      outcomes (presence/absence of polycystic ovarian syndrome). Polycystic ovarian
      syndrome was diagnosed if a patient had at least one other of the following two
      criteria: oligo/chronic anovulation and/or clinical/biochemical hyperandrogenism.
      A logistic regression model was constructed using stepwise selection to identify
      variables significantly associated with polycystic ovarian syndrome (p < .05).
      The validity of the model was assessed using receiver operating characteristics
      and Hosmer-Lemeshow chi(2) analyses. RESULTS: One hundred twenty-eight patients
      met official sonographic criteria for polycystic ovaries and 115 (89.8%) had
      polycystic ovarian syndrome (p = .009). Lower gravidity, abnormal bleeding, and
      body mass index >33 were significant in predicting polycystic ovarian syndrome
      (receiver operating characteristics curve, c = 0.86). Pain decreased the
      likelihood of polycystic ovarian syndrome. CONCLUSIONS: Polycystic ovaries on
      ultrasound were sensitive in predicting polycystic ovarian syndrome. Ultrasound,
      combined with clinical parameters, can be used to generate a predictive index for
      polycystic ovarian syndrome.

PMID- 24898322
TI  - Infrared photodissociation spectroscopy of oxygen-rich Fe(O2)n(+) (n = 3-5)
      cation complexes.
AB  - Infrared spectra of mass-selected oxygen-rich iron dioxygen complexes Fe(O2)n(+)
      with n = 3-5 are measured via infrared photodissociation spectroscopy in the gas
      phase. These cation complexes are produced via a laser vaporization supersonic
      ion source. The structures are established by comparison of the experimental
      spectra with the simulated spectra derived from density functional calculations.
      All of the Fe(O2)n(+) complexes studied have a single IR-active band in the 1050
      1100 cm(-1) region, arising from the O-O stretching vibration of the superoxo
      ligand(s). These complexes are determined to have structures with a chemically
      bound Fe(O2)2(+) core ion that is weakly coordinated by neutral O2 molecules. The
      Fe(O2)2(+) core ion has a planar D2h symmetry with two equivalent side-on
      superoxo ligands bound to an Fe(3+) cation center. 

PMID- 24898324
TI  - Versatile preparation of nonspherical multiple hydrogel core PAM/PEG emulsions
      and hierarchical hydrogel microarchitectures.
AB  - The preparation of nonspherical materials composed of separated multicomponents
      by droplet-based microfluidics remains a challenge. Based on polymerization
      induced phase separation and droplet coalescence in microfluidics, we prepared
      emulsions of variously shaped PAM/PEG core/shell droplets and hydrogels composed
      of two separated components, which show flexible and transformable hierarchical
      structures and microarchitectures. We find that AM/PEG aqueous droplets form a
      core/shell structure after polymerization resulting from phase separation. Thus
      multicore/shell droplets are easily produced by coalescence of core/shell
      structures. By changing the polymerization temperature and the flow rate, the
      morphology of the multicore droplets and the hydrogel can be easily adjusted. The
      hydrogels exhibit apparent anisotropy and different protein release rates
      depending on their structures. The preparation technique is simple and versatile
      and the resulting hydrogels have potential applications in many fields. 

PMID- 24898323
TI  - Effects of neonatal enzyme replacement therapy and simvastatin treatment on
      cervical spine disease in mucopolysaccharidosis I dogs.
AB  - Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by
      deficient alpha-L-iduronidase activity, leading to the accumulation of poorly
      degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of
      spine disease, including accelerated disc degeneration and vertebral dysplasia,
      which in turn lead to spinal cord compression and kyphoscoliosis. In this study
      we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone
      or in combination with oral simvastatin (ERT + SIM) for attenuating cervical
      spine disease progression in MPS I, using a canine model. Four groups were
      studied: normal controls; MPS I untreated; MPS I ERT-treated; and MPS I ERT + SIM
      treated. Animals were euthanized at age 1 year. Intervertebral disc condition and
      spinal cord compression were evaluated from magnetic resonance imaging (MRI)
      images and plain radiographs, vertebral bone condition and odontoid hypoplasia
      were evaluated using micro-computed tomography (uCT), and epiphyseal cartilage to
      bone conversion was evaluated histologically. Untreated MPS I animals exhibited
      more advanced disc degeneration and more severe spinal cord compression than
      normal animals. Both treatment groups resulted in partial preservation of disc
      condition and cord compression, with ERT + SIM not significantly better than ERT
      alone. Untreated MPS I animals had significantly lower vertebral trabecular bone
      volume and mineral density, whereas ERT treatment resulted in partial
      preservation of these properties. ERT + SIM treatment demonstrated similar, but
      not greater, efficacy. Both treatment groups partially normalized endochondral
      ossification in the vertebral epiphyses (as indicated by absence of persistent
      growth plate cartilage), and odontoid process size and morphology. These results
      indicate that ERT begun from a very early age attenuates the severity of cervical
      spine disease in MPS I, particularly for the vertebral bone and odontoid process,
      and that additional treatment with simvastatin does not provide a significant
      additional benefit over ERT alone.

PMID- 24898325
TI  - Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines
      against B. ovis infection.
AB  - Brucella ovis causes ram contagious epididymitis, a disease for which a specific
      vaccine is lacking. Attenuated Brucella melitensis Rev 1, used as vaccine against
      ovine and caprine brucellosis caused by B. melitensis, is also considered the
      best vaccine available for the prophylaxis of B. ovis infection, but its use for
      this purpose has serious drawbacks. In this work, two previously characterized B.
      ovis attenuated mutants (Deltaomp25d and Deltaomp22) were evaluated in mice, in
      comparison with B. melitensis Rev 1, as vaccines against B. ovis. Similarities,
      but also significant differences, were found regarding the immune response
      induced by the three vaccines. Mice vaccinated with the B. ovis mutants developed
      anti-B. ovis antibodies in serum of the IgG1, IgG2a and IgG2b subclasses and
      their levels were higher than those observed in Rev 1-vaccinated mice. After an
      antigen stimulus with B. ovis cells, splenocytes obtained from all vaccinated
      mice secreted similar levels of TNF-alpha and IL12(p40) and remarkably high
      amounts of IFN-gamma, a crucial cytokine in protective immunity against other
      Brucella species. By contrast, IL-1alpha -an enhancer of T cell responses to
      antigen- was present at higher levels in mice vaccinated with the B. ovis
      mutants, while IL-10, an anti-inflammatory cytokine, was significantly more
      abundant in Rev 1-vaccinated mice. Additionally, the B. ovis mutants showed
      appropriate persistence, limited splenomegaly and protective efficacy against B.
      ovis similar to that observed with B. melitensis Rev 1. These characteristics
      encourage their evaluation in the natural host as homologous vaccines for the
      specific prophylaxis of B. ovis infection.

PMID- 24898327
TI  - Attitudes towards seeking mental health services among older adults: personal and
      contextual correlates.
AB  - OBJECTIVES: Especially older adults underutilize professional mental health
      services. However, little is known about the factors associated with older
      adults' attitudes towards seeking mental health services (ATSMHS). We therefore
      investigated a wide range of contextual (e.g. physical access, residence) and
      personal (e.g. perceived social support, life satisfaction, openness to
      experience) predictors of ATSMHS in a sample of older community-dwelling adults
      in Germany. We predicted that representations of old age as well as perceptions
      of (younger) psychotherapists would be uniquely important for determining ATSMHS.
      METHOD: A diverse sample of N = 156 older adults (Mage = 71.5 years, SD = 6.4,
      range: 60-92) completed questionnaire measures. We used hierarchical linear
      regression analyses to identify predictors of ATSMHS. RESULTS: In the final
      saturated model, female gender, urban residence, personal and vicarious
      experience with psychotherapy, and higher perceived social support were each
      associated with more positive ATSMHS. In addition, more positive representations
      of old age and less negative perceptions of (younger) psychotherapists explained
      unique variance in ATSMHS over and above the other predictors. The overall model
      was significant and explained 49% of the variance in ATSMHS. CONCLUSION: Our
      findings can be used to inform interventions to improve older adults' ATSMHS.
      Interventions that seek to improve older adults' representations of their own
      aging as well as of psychotherapists may be useful for reducing the treatment
      gap.

PMID- 24898326
TI  - Mutagenicity and antimutagenicity of six Brazilian Byrsonima species assessed by
      the Ames test.
AB  - BACKGROUND: In various regions of Brazil, several species of the genus Byrsonima
      (Malpighiaceae) are widely used to treat gastrointestinal complications. This
      genus has about 150 species of shrubs and trees distributed over the entire
      Neotropical region. Various biological activities have been identified in these
      plants, especially antioxidant, antimicrobial and topical and systemic anti
      inflammatory activities. The aim of this study was to investigate the
      mutagenicity and antimutagenicity of hydroalcoholic leaf extracts of six species
      of Byrsonima: B. verbascifolia, B. correifolia, B. coccolobifolia, B.
      ligustrifolia, B. fagifolia and B. intermedia by the Salmonella microsome assay
      (Ames test). METHODS: Mutagenic and antimutagenic activity was assessed by the
      Ames test, with the Salmonella typhimurium tester strains TA100, TA98, TA97a and
      TA102, with (+S9) and without (-S9) metabolization, by the preincubation method.
      RESULTS: Only B. coccolobifolia and B. ligustrifolia showed mutagenic activity.
      However, the extracts of B. verbascifolia, B. correifolia, B. fagifolia and B.
      intermedia were found to be strongly antimutagenic against at least one of the
      mutagens tested. CONCLUSIONS: These results contribute to valuable data on the
      safe use of medicinal plants and their potential chemopreventive effects.
      Considering the excellent antimutagenic activities extracted from B.
      verbascifolia, B. correifolia, B. fagifolia and B. intermedia, these extracts are
      good candidate sources of chemopreventive agents. However, B. coccolobifolia and
      B. ligustrifolia showed mutagenic activity, suggesting caution in their use.

PMID- 24898328
TI  - Pitted keratolysis in an adolescent, diagnosed using conventional and molecular
      microbiology and successfully treated with fusidic acid.

PMID- 24898329
TI  - Physicians' attitudes toward medical and ethical challenges for patients in the
      vegetative state: comparing Canadian and German perspectives in a vignette
      survey.
AB  - BACKGROUND: Physicians treating patients in the vegetative state (VS) must deal
      with uncertainty in diagnosis and prognosis, as well as ethical issues. We
      examined whether physicians' attitudes toward medical and ethical challenges vary
      across two national medical practice settings. METHODS: A comparative survey was
      conducted among German and Canadian specialty physicians, based on a case
      vignette about the VS. Similarities and differences of participants' attitudes
      toward medical and ethical challenges between the two samples were analyzed with
      non-parametric tests (Mann-Whitney-U-Test). RESULTS: The overall response rate
      was 13.4%. Eighty percent of all participants correctly applied the diagnostic
      category of VS with no significant differences between countries. Many of the
      participants who chose the correct diagnosis of VS attributed capabilities to the
      patient, particularly the ability to feel pain (70%), touch (51%) and to
      experience hunger and thirst (35%). A large majority of participants (94%)
      considered the limitation of life-sustaining treatment (LST) under certain
      circumstances, but more Canadian participants were in favor of always limiting
      LST (32% vs. 12%; Chi-square: p < 0.001). Finding long-term care placement was
      considered more challenging by Canadian participants whereas discontinuing LST
      was much more challenging for German participants. CONCLUSIONS: Differences were
      found between two national medical practice settings with respect to physicians'
      experiences and attitudes about treatment limitation about VS in spite of
      comparable diagnostic knowledge.

PMID- 24898333
TI  - Rapid on-chip recalcification and drug dosing of citrated whole blood using
      microfluidic buffer sheath flow.
AB  - Millions of clotting tests each year require recalcification of blood treated
      with sodium citrate, a calcium chelator that prevents prothrombinase assembly. We
      validated a converging trifurcated microfluidic device to measure platelet and
      fibrin accumulation following on-chip recalcification of citrated whole blood.
      Recalcification was accomplished by sheathing the blood with Ca2+ buffer.
      Fluorescein rapidly diffused across the buffer-blood interface (achieving 62.5%
      of maximum centerline concentration within ~4 cm of flow), while albumin remained
      relatively unchanged in blood due to its lower diffusivity (<20% decrease). Since
      Ca2+ diffuses faster than fluorescein, full recalcification of whole blood was
      achieved within ~1 cm of flow prior to encountering a collagen/tissue surface.
      Platelet and fibrin were reduced by 87.3% and 99.0%, respectively, when the
      sheath buffer was Ca2+-free. A 30-min preincubation of citrated whole blood prior
      to on-chip recalcification increased platelet (159%) and fibrin (86.6%)
      deposition, compared to 5-min preincubation, likely due to factor XIIa generation
      in citrated blood. The P2Y1 inhibitor, MRS-2179, was delivered by diffusion into
      flowing blood and inhibited platelet deposition on collagen with a calculated
      IC50 of 0.155 MUM. On-chip recalcification and drug dosing of citrated blood
      allows for assays of platelet function in a whole blood milieu under flow. 

PMID- 24898331
TI  - Cytogenomic delineation and clinical follow-up of two siblings with an 8.5 Mb
      6q24.2-q25.2 deletion inherited from a paternal insertion.
AB  - The chromosomal segment 6q24-q25 comprises a contiguous gene microdeletion
      syndrome characterized by intrauterine growth retardation, growth delay,
      intellectual disability, cardiac anomalies, and a dysmorphic facial phenotype. We
      describe here a 10-year follow-up with detailed clinical, neuropsychological, and
      cytomolecular data of two siblings, male and female, who presented with
      developmental delay, microcephaly, short stature, characteristic facial
      dysmorphisms, multiple organ anomalies, and intellectual disability. Microarray
      analysis showed an 8.5 Mb 6q24.2-q25.2 interstitial deletion. Fluorescence in
      situ hybridization analyses confirmed the deletions and identified an insertion
      of 6q into 8q13 in their father, resulting in a high recurrence risk. This is the
      first report in sibs with distinct neuropsychological involvement, one of them
      with stenosis of the descending branch of the aorta.

PMID- 24898334
TI  - Shear sensitive microRNAs and atherosclerosis.
AB  - Atherosclerosis, the leading cause of morbidity and mortality in developed
      nations, is a chronic inflammatory disease of arteries. In large and medium-sized
      vessels, the atherosclerotic burden is focal and non-random, despite the systemic
      nature of risk factors. This observation has prompted numerous studies over the
      past two decades that have evaluated the relationship between blood flow,
      endothelial function and plaque localization. The recent discovery of microRNAs
      (miRNAs) that are sensitive to distinct flow conditions has added a new layer of
      complexity to the pathophysiology of atherosclerosis, but may ultimately help us
      better understand the disease process. In this manuscript we will briefly review
      the most commonly used in vitro and in vivo model systems developed to study the
      relationship between flow, endothelial function and plaque development. We will
      also provide a brief summary of shear sensitive miRNAs that have been shown to
      modulate inflammatory signaling pathways and atherosclerotic burden through
      changes in the endothelial gene expression. 

PMID- 24898335
TI  - Gender differences in hemorheological parameters and in in vitro platelet
      aggregation in acetylsalicylic acid and clopidogrel treated vascular patients.
AB  - BACKGROUND: Sex-specific response to antiplatelet medications have been reported
      in several previous studies. OBJECTIVE: We investigated a possible connection
      between gender differences in hemorheological parameters and in vitro platelet
      aggregation in vascular patients treated with widely used antiplatelet agents.
      METHODS: In vitro platelet aggregation was assessed in 2687 patients treated with
      100 mg acetylsalicylic acid (ASA), 1047 patients treated with 75 mg clopidogrel
      and 311 patients on dual antiplatelet therapy (100 mg aspirin and 75 mg
      clopidogrel) according to the method of Born. In subgroups of patients fibrinogen
      concentration, whole blood and plasma viscosity, red blood cell aggregation and
      hematocrit were simultaneously measured. The subjects were divided into groups
      according to their gender. RESULTS: ADP induced platelet aggregation was
      significantly higher in women in the case of ASA treatment (p<0.001). No gender
      differences could be observed in platelet function in patients treated with
      clopidogrel or on dual antiplatelet therapy. Hematocrit and whole blood viscosity
      were significantly higher in men in all groups (p<0.001), while no significant
      gender differences were observed in red blood cell aggregation indices in either
      group. Fibrinogen concentration was significantly higher in women than in men
      among patients treated with 100 mg ASA (p<0.05), but not in the other groups.
      CONCLUSIONS: Significantly higher fibrinogen concentration found in aspirin
      treated women than men may play a role in higher ADP induced platelet
      aggregation. Gender differences in response to monotherapy suggest that benefits
      from combination therapy may be greater in females. The clinical relevance of
      higher ADP induced platelet aggregation in women treated with ASA needs further
      investigation.

PMID- 24898337
TI  - Effect of clinical and RBC hemorheological parameters on myocardial perfusion in
      patients with type 2 diabetes mellitus.
AB  - Myocardial ischemia may be present even when there is no significant stenosis of
      the epicardial coronary artery, or after coronary angioplasty for significant
      coronary artery disease. This phenomenon is related to disturbance of the
      coronary microcirculation or vasomotor tone. The aim of this study was to
      determine the influence of clinical and RBC hemorheological factors, such as RBC
      deformability and aggregation, on myocardial perfusion in patients with type 2
      diabetes mellitus (DM) when compared to patients without DM, presenting with
      stable angina or acute coronary syndrome. Myocardial perfusion was graded using
      the myocardial blush grade (MBG) which describes the relative "blush" or
      intensity of the radio-opacity of myocardial tissue observed after an epicardial
      coronary injection of contrast medium during coronary angiography. MBG was
      counted before any medical or mechanical intervention, and in the myocardial
      territory without anatomical flow limitation (<50% of luminal narrowing on
      coronary angiogram), in order to remove the direct influence of anatomical
      stenosis. Myocardial perfusion in this region was associated with diabetes, renal
      function, LV diastolic function, inflammatory biomarkers such as hs-CRP,
      fibrinogen and ESR, but not with the clinical presentation. Among the
      hemorheological parameters, reduced myocardial perfusion was linked to increased
      RBC aggregation, but not to variation in RBC deformability. In conclusion,
      myocardial perfusion was affected by diabetes, left ventricular diastolic
      function, and inflammatory activity indicated by clinical parameters, and by the
      hemorheological factor RBC aggregation. 

PMID- 24898336
TI  - Deformability analysis of sickle blood using ektacytometry.
AB  - Sickle cell disease (SCD) is characterized by decreased erythrocyte
      deformability, microvessel occlusion and severe painful infarctions of different
      organs. Ektacytometry of SCD red blood cells (RBC) is made difficult by the
      presence of rigid, poorly-deformable irreversibly sickled cells (ISC) that do not
      align with the fluid shear field and distort the elliptical diffraction pattern
      seen with normal RBC. In operation, the computer software fits an outline to the
      diffraction pattern, then reports an elongation index (EI) at each shear stress
      based on the length and width of the fitted ellipse: EI=(length
      width)/(length+width). Using a commercial ektacytometer (LORCA, Mechatronics
      Instruments, The Netherlands) we have approached the problem of ellipse fitting
      in two ways: (1) altering the height of the diffraction image on a computer
      monitor using an aperture within the camera lens; (2) altering the light
      intensity level (gray level) used by the software to fit the image to an
      elliptical shape. Neither of these methods affected deformability results
      (elongation index-shear stress relations) for normal RBC but did markedly affect
      results for SCD erythrocytes: (1) decreasing image height by 15% and 30%
      increased EI at moderate to high stresses; (2) progressively increasing the light
      level increased EI over a wide range of stresses. Fitting data obtained at
      different image heights using the Lineweaver-Burke routine yielded percentage ISC
      results in good agreement with microscopic cell counting. We suggest that these
      two relatively simple approaches allow minimizing artifacts due to the presence
      of rigid discs or ISC and also suggest the need for additional studies to
      evaluate the physiological relevance of deformability data obtained via these
      methods. 

PMID- 24898338
TI  - The effect of pulsed IR-light on the rheological parameters of blood in vitro.
AB  - In this study we attempted to assess the effect of light of 855 nm wavelength (IR
      light) on the rheological parameters of blood in vitro. As an anticoagulant,
      heparin was used. The source of IR-light was an applicator connected to the
      special generator--Viofor JPS(r). The blood samples were irradiated for 30 min.
      During the irradiation the energy density was growing at twelve-second intervals
      starting from 1.06 J/cm2 to 8.46 J/cm2, then the energy density dropped to the
      initial value; the process was repeated cyclically. The study of blood viscosity
      was carried out with a Contraves LS40 oscillatory-rotational rheometer, with a
      decreasing shearing rate from 100 to 0.01 s-1 over 5 min (flow curve) and
      applying constant frequency oscillations f=0.5 Hz with decreasing shear amplitude
      gamma0 (viscoelasticity measurements). The analysis of the results of rotational
      measurements was based on the assessment of hematocrit, plasma viscosity, whole
      blood viscosity at four selected shear rates and on the basis of the numerical
      values of parameters from Quemada's rheological model: k0 (indicating red cell
      aggregability), kinfinity (indicating red cell rigidity) and gammac (the value of
      the shear rate for which the rouleaux formation begins). In oscillatory
      experiments we estimated viscous and elastic components of the complex blood
      viscosity in the same groups of patients. We observed a decrease of the viscous
      component of complex viscosity (eta') at gamma0=0.2 s-1, while other rheological
      parameters, k0, kinfinity, and relative blood viscosity at selected shear rates
      showed only a weak tendency towards smaller values after irradiation. The IR
      light effect on the rheological properties of blood in vitro turned out to be
      rather neutral in the studied group of patients.

PMID- 24898339
TI  - Evaluating interactive computer-based scenarios designed for learning medical
      technology.
AB  - The use of medical equipment is growing in healthcare, resulting in an increased
      need for resources to educate users in how to manage the various devices.
      Learning the practical operation of a device is one thing, but learning how to
      work with the device in the actual clinical context is more challenging. This
      paper presents a computer-based simulation prototype for learning medical
      technology in the context of critical care. Properties from simulation and
      computer games have been adopted to create a visualization-based, interactive and
      contextually bound tool for learning. A participatory design process, including
      three researchers and three practitioners from a clinic for infectious diseases,
      was adopted to adjust the form and content of the prototype to the needs of the
      clinical practice and to create a situated learning experience. An evaluation
      with 18 practitioners showed that practitioners were positive to this type of
      tool for learning and that it served as a good platform for eliciting and sharing
      knowledge. Our conclusion is that this type of tools can be a complement to
      traditional learning resources to situate the learning in a context without
      requiring advanced technology or being resource-demanding. 

PMID- 24898340
TI  - On the persuadability of memory: Is changing people's memories no more than
      changing their minds?
AB  - The observation of parallels between the memory distortion and persuasion
      literatures leads, quite logically, to the appealing notion that people can be
      'persuaded' to change their memories. Indeed, numerous studies show that memory
      can be influenced and distorted by a variety of persuasive tactics, and the
      theoretical accounts commonly used by researchers to explain episodic and
      autobiographical memory distortion phenomena can generally predict and explain
      these persuasion effects. Yet, despite these empirical and theoretical overlaps,
      explicit reference to persuasion and attitude-change research in the memory
      distortion literature is surprisingly rare. In this paper, we argue that stronger
      theoretical foundations are needed to draw the memory distortion and persuasion
      literatures together in a productive direction. We reason that theoretical
      approaches to remembering that distinguish (false) beliefs in the occurrence of
      events from (false) memories of those events - compatible with a source
      monitoring approach - would be beneficial to this end. Such approaches, we argue,
      would provide a stronger platform to use persuasion findings to enhance the
      psychological understanding of memory distortion.

PMID- 24898341
TI  - Smart pH- and reduction-dual-responsive folate-PEG-coated polymeric lipid
      vesicles for tumor-triggered targeted drug delivery.
AB  - To improve their therapeutic index, designed nanocarriers should preferentially
      accumulate in tumor tissues and then rapidly enter tumor cells to release the
      encapsulated drugs in a triggered manner. In this article, a new kind of a smart
      pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated
      polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was
      designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds,
      stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate
      were connected to a dextran main chain. The newly developed FPPLVs had a nano
      sized structure (~50 nm) with a PEG coating. The in vitro DOX release profiles
      showed that the FPPLVs achieved a triggered drug release in response to acidic pH
      and reducing environments due to the cleavage of hydrazone bonds and disulfide
      bonds. It has also been demonstrated by an in vitro cellular uptake study that
      the FPPLVs lose their PEG coating as well as expose the folate in acidic
      conditions, which allows them to efficiently enter tumor cells through ligand
      receptor interactions. In vitro cytotoxicity measurements also confirmed that
      FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results
      suggest that FPPLVs are promising carriers for smart antitumor drug delivery
      applications. 

PMID- 24898343
TI  - Early indicators of cervical insufficiency assessed using magnetic resonance
      imaging of the cervix during pregnancy.
AB  - OBJECTIVE: To establish the main characteristics of the cervix in pregnant women
      with cervical insufficiency, by means of magnetic resonance imaging (MRI).
      METHODS: A prospective observational case-control study was conducted among 59
      pregnant women with cervical insufficiency and 10 normal pregnant women, between
      their 10th and 28th weeks. The parameters analyzed in the MRI examinations were:
      precise identification of the cervix; presence of hyposignal at the internal
      orifice of the cervix; loss of definition of the periendocervical stromal zone
      (PESZ); presence of hyposignal content inside the amniotic sac (sludge sign) and
      anatomical and functional biometry of the cervix. RESULTS: Peripheral hyposignal
      was found in 41 (85.4%) and loss of definition of the PESZ was observed in 36
      pregnant women (73.5%) with cervical insufficiency. Sludge was observed in 46
      pregnant women with cervical insufficiency, and this was seen on MRI in 27 cases
      (58.7%). The mean anatomical and functional lengths of the cervix on MRI in the
      pregnant women with cervical insufficiency were 3.5 +/- 0.8 cm (0.8-4.9 cm) and
      28.7 +/- 6.3 mm (9-41 mm). None of the normal pregnant women presented hyposignal
      loss of the PESZ and the sludge sign. CONCLUSION: MRI may be useful for
      evaluating the cervix and for early identification of signs of cervical
      insufficiency during pregnancy.

PMID- 24898342
TI  - Intensive care unit admission in chronic obstructive pulmonary disease: patient
      information and the physician's decision-making process.
AB  - INTRODUCTION: ICU admission is required in more than 25% of patients with chronic
      obstructive pulmonary disease (COPD) at some time during the course of the
      disease. However, only limited information is available on how physicians
      communicate with COPD patients about ICU admission. METHODS: COPD patients and
      relatives from 19 French ICUs were interviewed at ICU discharge about their
      knowledge of COPD. French pulmonologists self-reported their practices for
      informing and discussing intensive care treatment preferences with COPD patients.
      Finally, pulmonologists and ICU physicians reported barriers and facilitators for
      transfer of COPD patients to the ICU and to propose invasive mechanical
      ventilation. RESULTS: Self-report questionnaires were filled in by 126 COPD
      patients and 102 relatives, and 173 pulmonologists and 135 ICU physicians were
      interviewed. For 41% (n = 39) of patients and 54% (n = 51) of relatives, ICU
      admission had never been expected prior to admission. One half of patients were
      not routinely informed by their pulmonologist about possible ICU admission at
      some time during the course of COPD. Moreover, treatment options (that is, non
      invasive ventilation, intubation and mechanical ventilation or tracheotomy) were
      not explained to COPD patients during regular pulmonologist visits.
      Pulmonologists and ICU physician have different perceptions of the decision
      making process pertaining to ICU admission and intubation. CONCLUSIONS: The
      information provided by pulmonologists to patients and families concerning the
      prognosis of COPD, the risks of ICU admission and specific care could be improved
      in order to deliver ICU care in accordance with the patient's personal values and
      preferences. Given the discrepancies in the decision-making process between
      pulmonologists and intensivists, a more collaborative approach should probably be
      discussed.

PMID- 24898344
TI  - Demodex folliculorum: its association with oily skin surface rather than rosacea
      lesions.
AB  - BACKGROUND: Despite the predilection of Demodex folliculorum (DF) for human
      sebum, observational studies addressing a relationship between this agent and
      rosacea paid no attention to the effect of a potentially acting confounder, the
      oily nature of the skin. OBJECTIVES: To analyze whether a relationship exists
      between the presence of the mite in rosacea and oily cutis. MATERIALS AND
      METHODS: An observational study on 63 rosacea cases and 61 healthy controls, both
      discriminated according to their predominance of oily or dry cutis, was carried
      out to investigate demodectic density by the skin surface biopsy. RESULTS: While
      comparisons on the density of DF revealed no differences between patients and
      controls (Mann-Whitney U-test, P = 0.35), persons with an oily cutis had
      increased amounts of this mite on the skin surface (Mann-Whitney U-test, P <
      0.05), irrespective of whether they had rosacea or not. CONCLUSIONS: The
      association between DF and oily skin rather than rosacea lesions gives no support
      for this agent being implied in disease pathogenesis.

PMID- 24898345
TI  - Ultrasound-modulated bubble propulsion of chemically powered microengines.
AB  - The use of an ultrasound (US) field for rapid and reversible control of the
      movement of bubble-propelled chemically powered PEDOT/Ni/Pt microengines is
      demonstrated. Such operation reflects the US-induced disruption of normal bubble
      evolution and ejection, essential for efficient propulsion of catalytic
      microtubular engines. It offers precise speed control, with sharp increases and
      decreases of the speed at low and high US powers, respectively. A wide range of
      speeds can thus be generated by tuning the US power. Extremely fast changes in
      the motor speed (<0.1 s) and reproducible "On/Off" activations are observed,
      indicating distinct advantages compared to motion control methods based on other
      external stimuli. Such effective control of the propulsion of chemically powered
      microengines, including remarkable "braking" ability, holds considerable promise
      for diverse applications. 

PMID- 24898346
TI  - Follicular mucinosis associated with pregnancy.

PMID- 24898347
TI  - High prevalence of inappropriate urine drug tests in a pain clinic for patients
      with HIV.

PMID- 24898349
TI  - (Electro)catalytic C-C bond formation reaction with a redox-active cobalt
      complex.
AB  - Cooperativity between cobalt and non-innocent ligands in electron transfer
      processes has been utilized for (electro)catalytic C-C bond formation reactions. 

PMID- 24898348
TI  - Comparison of the vector potential of different mosquito species for the
      transmission of heartworm, Dirofilaria immitis, in rural and urban areas in and
      surrounding Stillwater, Oklahoma, U.S.A.
AB  - Dirofilaria immitis Leidy (Spirurida: Onchocercidae), or heartworm, is a mosquito
      borne nematode that causes a fatal disease in carnivores. Although infection is
      preventable through prophylactic drugs, compliance and the spectre of resistance
      suggest vector control is a viable alternative. There were two main objectives in
      this study: (a) to evaluate the relationships between landscape and social
      factors and the number and species of heartworm-positive mosquitoes, with a
      specific focus on the importance of the invasive Asian tiger mosquito, Aedes
      albopictus (Skuse) (Stegomyia albopicta) (Diptera: Culicidae), and (b) to test
      the hypothesis that dog heartworm is more prevalent in suburban than in rural
      areas. To achieve these objectives, mosquitoes were collected from May to
      November 2010 at 16 rural and 16 urban locations in Payne County, Oklahoma,
      U.S.A. using three trapping methods that utilized, respectively, resting boxes,
      carbon dioxide traps and BG Sentinel traps. Urban areas showed greater numbers of
      Ae. albopictus and a higher overall likelihood of infection with D. immitis.
      Because many species of mosquito are responsible for heartworm transmission,
      current prophylactic treatment remains the best method of controlling this
      parasite. 

PMID- 24898350
TI  - Preparation of uniform particle-stabilized emulsions using SPG membrane
      emulsification.
AB  - Various aspects of particle-stabilized emulsions (or so-called Pickering
      emulsions) have been extensively investigated during the last two decades, but
      the preparation of uniform Pickering emulsion droplets via a simple and scalable
      method has been sparingly realized. We report the preparation of uniform
      Pickering emulsions by Shirasu porous glass (SPG) membrane emulsification. The
      size of the emulsion droplets ranging from 10-50 MUm can be precisely controlled
      by the size of the membrane pore. The emulsion droplets have a high
      monodispersity with coefficients of variation (CV) lower than 15% in all of the
      investigated systems. We further demonstrate the feasibility of locking the
      assembled particles at the interface, and emulsion droplets have been shown to be
      excellent templates for the preparation of monodisperse colloidosomes that are
      necessary in drug-delivery systems. 

PMID- 24898353
TI  - The Lived Experience of Female Veterans Deployed to the Gulf War II.
AB  - PURPOSE: The purpose of this inquiry is to discover the experiences of female
      veterans in order to understand the impacts of combat on their physical and
      mental health, and to shed light on directions for future research. The research
      question for this inquiry is: What is the lived experience of female combat
      veterans who deployed to Iraq and Afghanistan from 2001 through 2013? METHODS:
      The methodology used in this qualitative inquiry is a descriptive
      phenomenological approach using Husserl's philosophical framework. Colaizzi's
      method was used for data analysis. FINDINGS: Analysis revealed seven themes:
      living in constant fear while deployed, combat has different meanings, bringing
      the war home, fear of being forever changed, disrespect from fellow military
      members, physical health-for better or worse, and combat has rewarding
      experiences. CONCLUSION: Early detection and assessment is crucial to providing
      interventions to military veterans to reduce the invisible wound of war,
      posttraumatic stress disorder, and ultimately increase the quality of life.

PMID- 24898352
TI  - The feature of metabolic syndrome is a risk factor for biochemical recurrence
      after radical prostatectomy.
AB  - BACKGROUND AND OBJECTIVE: To examine the association between the features of
      metabolic syndrome (MetS) (obesity, hypertension, diabetes mellitus, and
      dyslipidemia) and the risk of biochemical recurrence (BCR) after radical
      prostatectomy in patients with prostate cancer. METHODS: This study included 283
      Japanese patients with localized prostate cancer who were treated with radical
      prostatectomy between 2008 and 2012. Their oncological outcomes and the
      prognostic significance of several clinicopathological factors, as well as the
      features of MetS, were analyzed. RESULTS: Of 283 men who underwent radical
      prostatectomy, 49 (17.2%) subsequently developed BCR with a median postoperative
      follow-up of 14.8 months. Among the clinicopathological factors, prostate
      specific antigen (PSA) level at diagnosis, pathological stage, pathological
      Gleason score, and lymph-node involvement were independent risk factors for BCR
      in multivariate analysis. In addition, the number of metabolic risk factors was
      also an independent risk factor for BCR. CONCLUSIONS: The features of MetS were
      linked with poorer outcome after radical prostatectomy among Japanese men.
      Further investigations are needed to determine the effect of improving MetS on
      prostate cancer prognosis.

PMID- 24898354
TI  - Relationship between arterial stiffening and skeletal muscle atrophy in
      hemodialysis patients: a gender comparative study.

PMID- 24898355
TI  - Left ventricular mass correlates with lean body mass in patients with disease
      associated wasting.

PMID- 24898356
TI  - Erratum to: Assessing sarcopenic prevalence and risk factors in residential aged
      care: methodology and feasibility.

PMID- 24898351
TI  - Endoplasmic reticulum stress in spinal and bulbar muscular atrophy: a potential
      target for therapy.
AB  - Spinal and bulbar muscular atrophy is an X-linked degenerative motor neuron
      disease caused by an abnormal expansion in the polyglutamine encoding CAG repeat
      of the androgen receptor gene. There is evidence implicating endoplasmic
      reticulum stress in the development and progression of neurodegenerative disease,
      including polyglutamine disorders such as Huntington's disease and in motor
      neuron disease, where cellular stress disrupts functioning of the endoplasmic
      reticulum, leading to induction of the unfolded protein response. We examined
      whether endoplasmic reticulum stress is also involved in the pathogenesis of
      spinal and bulbar muscular atrophy. Spinal and bulbar muscular atrophy mice that
      carry 100 pathogenic polyglutamine repeats in the androgen receptor, and develop
      a late-onset neuromuscular phenotype with motor neuron degeneration, were
      studied. We observed a disturbance in endoplasmic reticulum-associated calcium
      homeostasis in cultured embryonic motor neurons from spinal and bulbar muscular
      atrophy mice, which was accompanied by increased endoplasmic reticulum stress.
      Furthermore, pharmacological inhibition of endoplasmic reticulum stress reduced
      the endoplasmic reticulum-associated cell death pathway. Examination of spinal
      cord motor neurons of pathogenic mice at different disease stages revealed
      elevated expression of markers for endoplasmic reticulum stress, confirming an
      increase in this stress response in vivo. Importantly, the most significant
      increase was detected presymptomatically, suggesting that endoplasmic reticulum
      stress may play an early and possibly causal role in disease pathogenesis. Our
      results therefore indicate that the endoplasmic reticulum stress pathway could
      potentially be a therapeutic target for spinal and bulbar muscular atrophy and
      related polyglutamine diseases. 

PMID- 24898357
TI  - Porous molecular networks formed by the self-assembly of positively-charged
      trigonal building blocks at the liquid/solid interfaces.
AB  - Tris-(2-hydroxybenzylidene)triaminoguanidinium salts having six alkyl chains with
      proper spacing served as new molecular building blocks for the formation of
      porous honeycomb networks by van der Waals interaction between interdigitated
      alkyl chains at the liquid/graphite interfaces. 

PMID- 24898358
TI  - Nuclear Localization Signal-Enhanced Polyurethane-Short Branch Polyethylenimine
      Mediated Delivery of Let-7a Inhibited Cancer Stem-Like Properties by Targeting
      the 3'-UTR of HMGA2 in Anaplastic Astrocytoma.
AB  - Anaplastic astrocytoma (AA) is a grade III glioma that often occurs in middle
      aged patients and presents a uniformly poor prognosis. A small subpopulation of
      cancer stem cells (CSCs) possessing a self-renewing capacity is reported to be
      responsible for tumor recurrence and therapeutic resistance. An accumulating
      amount of microRNAs (miRNA) were found aberrantly expressed in human cancers and
      regulate CSCs. Efforts have been made to couple miRNAs with nonviral gene
      delivery approaches to target specific genes in cancer cells. However, the
      efficiency of delivery of miRNAs to AA-derived CSCs is still an applicability
      hurdle. The present study aimed to investigate the effectiveness and
      applicability of nonviral vector-mediated delivery of Let-7a with regard to
      eradication of AA and AA-derived CSC cells. Herein, our miRNA/mRNA microarray and
      RT-PCR analysis showed that the expression of Let-7a, a tumor-suppressive miRNA,
      is inversely correlated with the levels of HMGA2 and Sox2 in the AA side
      population (SP(+)) cells. Luciferase reporter assay showed that Let-7a directly
      targets the 3'-UTRs of HMGA2 in AA-SP(+) cells. Knockdown of HMGA2 significantly
      suppressed the protein expression of Sox2 in AA-SP(+) cells, whereas
      overexpression of HMGA2 upregulated Sox2 expression in AA-SP(-). Nuclear
      localization signal (NLS) peptides can facilitate nuclear targeting of DNA and
      are used to improve gene delivery. Using polyurethane-short branch
      polyethylenimine (PU-PEI) as a therapeutic delivery vehicle, we conjugated NLS
      with Let-7 and successfully delivered it to AA-SP(+) cells, resulting in
      significantly suppressed expression of HMGA2 and Sox2, tumorigenicity, and CSC
      like abilities. This treatment facilitated the differentiation of AA-SP(+) cells
      into non-SP CSCs. Furthermore, PU-PEI-mediated delivery of NLS-conjugated Let-7a
      in AA-SP(+) cells suppressed the expression of drug-resistant and antiapoptotic
      genes, and increased cell sensitivity to radiation. Finally, the in vivo delivery
      of PU-PEI-NLS-Let-7a significantly suppressed the tumorigenesis of AA-SP(+) cells
      and synergistically improved the survival rate of orthotopically AA-SP(+)
      transplanted immunocompromised mice when combined with radiotherapy. Therefore,
      PU-PEI-NLS-Let-7a is a potential novel therapeutic approach for AA. 

PMID- 24898359
TI  - The role of a proliferation-inducing ligand (APRIL) in the pathogenesis of
      rheumatoid arthritis.
AB  - OBJECTIVES: To determine the differences in a proliferation-inducing ligand
      (APRIL) between seropositive and seronegative rheumatoid arthritis (RA) patients
      and further investigate the possible pathogenesis of the two subtypes of RA.
      METHOD: Concentrations of APRIL in sera (18 seropositive RA patients, 16
      seronegative RA patients, and 10 healthy controls) and synovial fluid (SF) (eight
      seropositive RA patients, two seronegative RA patients, and 10 controls) were
      detected by enzyme-linked immunosorbent assay (ELISA). Infiltration of plasma
      cells, macrophages, and APRIL-positive cells in the synovium [14 seropositives,
      eight seronegatives, and 10 osteoarthritis (OA) controls] was detected by
      immunohistochemistry. Correlations between serum C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28),
      and sera/SF levels of APRIL and synovial cell infiltration were analysed.
      RESULTS: The mean serum APRIL level of seropositive RA patients was significantly
      higher than that of seronegative patients (26.1 +/- 31.2 vs. 8.0 +/- 10.2 ng/mL,
      p = 0.03). The level of APRIL in the SF of seropositive RA patients was
      comparable to that of seronegative patients [47.9 +/- 54.4 vs. 32.82 (6.52-59.12)
      ng/mL, p > 0.05]. The SF APRIL level of RA patients was higher than that of
      patients with other inflammatory arthritis. Dramatically increased infiltration
      of APRIL-positive cells in the RA synovium was observed compared with the OA
      group (seropositive RA vs. OA, p < 0.001; seronegative RA vs. OA, p = 0.001). The
      infiltration of both plasma cells and macrophages was more in seropositive RA
      than in OA (p = 0.013 and p = 0.003, respectively). CONCLUSIONS: The serum APRIL
      levels of seropositive RA patients are significantly higher than those of
      seronegative RA patients. APRIL may participate in the formation of seropositive
      RA.

PMID- 24898360
TI  - Risk of stroke in patients with rheumatism: a nationwide longitudinal population
      based study.
AB  - The aim of this study was to investigate rheumatoid arthritis (RA), and systemic
      lupus erythematous (SLE) as risk factors for stroke. The study was analyzed by
      Using the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005), this
      cohort study investigated patients with a recorded diagnosis of RA (N = 6114),
      and SLE (N = 621) between January 1, 2004, and December 31, 2007, with age
      matched controls (1:4) (for RA, N = 24456; SLE, N = 2484). We used Cox
      proportional-hazard regressions to evaluate the hazard ratios (HRs) after
      adjusting confounding factors. Our study found 383 of 6114 RA patients,
      experienced stroke during the 20267 person-year follow-up period. The adjusted HR
      of stroke for RA patients was 1.24 (95% CI, 1.11 to 1.39), and for SLE patients
      was 1.88 (95% CI, 1.08 to 3.27). When steroid was added as additional confounding
      factor, the adjusted HR of ischemic stroke for RA patients was 1.32 (95% CI, 1.15
      to 1.50), and for SLE patients was 1.31 (95% CI, 0.51 to 3.34). In conclusion,
      the rheumatic diseases of RA, and SLE are all risk factors for stroke. After
      controlled the effect of steroid prescription, RA is risk factor for ischemic
      stroke. 

PMID- 24898362
TI  - Misregulation of spermatogenesis genes in Drosophila hybrids is lineage-specific
      and driven by the combined effects of sterility and fast male regulatory
      divergence.
AB  - Hybrid male sterility is a common outcome of crosses between different species.
      Gene expression studies have found that a number of spermatogenesis genes are
      differentially expressed in sterile hybrid males, compared with parental species.
      Late-stage sperm development genes are particularly likely to be misexpressed,
      with fewer early-stage genes affected. Thus, a link has been posited between
      misexpression and sterility. A more recent alternative explanation for hybrid
      gene misexpression has been that it is independent of sterility and driven by
      divergent evolution of male-specific regulatory elements between species (faster
      male hypothesis). The faster male hypothesis predicts that misregulation of
      spermatogenesis genes should be independent of sterility and approximately the
      same in both hybrids, whereas sterility should only affect gene expression in
      sterile hybrids. To test the faster male hypothesis vs. the effect of sterility
      on gene misexpression, we analyse spermatogenesis gene expression in different
      species pairs of the Drosophila phylogeny, where hybrid male sterility occurs in
      only one direction of the interspecies cross (i.e. unidirectional sterility). We
      find significant differences among genes in misexpression with effects that are
      lineage-specific and caused by sterility or fast male regulatory divergence.

PMID- 24898361
TI  - Evidence-based feeding strategies before and after the development of necrotizing
      enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a devastating disease of premature infants and
      is associated with significant morbidity and mortality. While the pathogenesis of
      NEC remains incompletely understood, it is well established that the risk of
      disease is increased by the administration of infant formula and decreased by the
      administration of breast milk. This review will focus on the mechanisms by which
      breast milk may serve to protect against NEC, and will review the evidence
      regarding various feeding strategies that may be utilized before and after an
      episode of NEC.

PMID- 24898363
TI  - An electronic health records study of long-term weight gain following
      antidepressant use.
AB  - IMPORTANCE: Short-term studies suggest antidepressants are associated with modest
      weight gain but little is known about longer-term effects and differences between
      individual medications in general clinical populations. OBJECTIVE: To estimate
      weight gain associated with specific antidepressants over the 12 months following
      initial prescription in a large and diverse clinical population. DESIGN, SETTING,
      AND PARTICIPANTS: We identified 22,610 adult patients who began receiving a
      medication of interest with available weight data in a large New England health
      care system, including 2 academic medical centers and affiliated outpatient
      primary and specialty care clinics. We used electronic health records to extract
      prescribing data and recorded weights for any patient with an index
      antidepressant prescription including amitriptyline hydrochloride, bupropion
      hydrochloride, citalopram hydrobromide, duloxetine hydrochloride, escitalopram
      oxalate, fluoxetine hydrochloride, mirtazapine, nortriptyline hydrochloride,
      paroxetine hydrochloride, venlafaxine hydrochloride, and sertraline
      hydrochloride. As measures of assay sensitivity, additional index prescriptions
      examined included the antiasthma medication albuterol sulfate and the antiobesity
      medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride.
      Mixed-effects models were used to estimate rate of weight change over 12 months
      in comparison with the reference antidepressant, citalopram. MAIN OUTCOME AND
      MEASURE: Clinician-recorded weight at 3-month intervals up to 12 months. RESULTS:
      Compared with citalopram, in models adjusted for sociodemographic and clinical
      features, significantly decreased rate of weight gain was observed among
      individuals treated with bupropion (beta [SE]: -0.063 [0.027]; P = .02),
      amitriptyline (beta [SE]: -0.081 [0.025]; P = .001), and nortriptyline (beta
      [SE]: -0.147 [0.034]; P < .001). As anticipated, differences were less pronounced
      among individuals discontinuing treatment prior to 12 months. CONCLUSIONS AND
      RELEVANCE: Antidepressants differ modestly in their propensity to contribute to
      weight gain. Short-term investigations may be insufficient to characterize and
      differentiate this risk.

PMID- 24898364
TI  - The feeding practices and structure questionnaire: construction and initial
      validation in a sample of Australian first-time mothers and their 2-year olds.
AB  - BACKGROUND: Early feeding practices lay the foundation for children's eating
      habits and weight gain. Questionnaires are available to assess parental feeding
      but overlapping and inconsistent items, subscales and terminology limit
      conceptual clarity and between study comparisons. Our aim was to consolidate a
      range of existing items into a parsimonious and conceptually robust questionnaire
      for assessing feeding practices with very young children (<3 years). METHODS:
      Data were from 462 mothers and children (age 21-27 months) from the NOURISH
      trial. Items from five questionnaires and two study-specific items were submitted
      to a priori item selection, allocation and verification, before theoretically
      derived factors were tested using Confirmatory Factor Analysis. Construct
      validity of the new factors was examined by correlating these with child eating
      behaviours and weight. RESULTS: Following expert review 10 factors were
      specified. Of these, 9 factors (40 items) showed acceptable model fit and
      internal reliability (Cronbach's alpha: 0.61-0.89). Four factors reflected non
      responsive feeding practices: 'Distrust in Appetite', 'Reward for Behaviour',
      'Reward for Eating', and 'Persuasive Feeding'. Five factors reflected structure
      of the meal environment and limits: 'Structured Meal Setting', 'Structured Meal
      Timing', 'Family Meal Setting', 'Overt Restriction' and 'Covert Restriction'.
      Feeding practices generally showed the expected pattern of associations with
      child eating behaviours but none with weight. CONCLUSION: The Feeding Practices
      and Structure Questionnaire (FPSQ) provides a new reliable and valid measure of
      parental feeding practices, specifically maternal responsiveness to children's
      hunger/satiety signals facilitated by routine and structure in feeding. Further
      validation in more diverse samples is required.

PMID- 24898366
TI  - Patient self-assessment of chronic wounds.

PMID- 24898365
TI  - Therapeutic management of anal eczema: an evidence-based review.
AB  - AIM: To conduct a systematic review of treatments for anal eczema (AE). METHODS:
      We conducted a Medline search for clinical trial data for the treatment of
      perianal diseases including AE, including papers not published in the English
      language. We assessed the study reports using the system recommended by the
      Oxford Centre for Evidence-based Medicine. No meta-analysis was attempted.
      RESULTS: The evidence base for topical treatments used to treat AE is very poor:
      there are very few studies and many of those that exist are of poor quality. The
      best evidence was found for medications that are yet to be licensed for AE. Among
      products with existing licences for the treatment of eczema, our assessment found
      some evidence to support the continued use of mild-to-moderate corticosteroids
      first line in most patients. DISCUSSION: Features of the perianal region, and the
      fact that it is almost always occluded, mean that not all medications recommended
      in the general treatment guidelines for eczema are appropriate for AE. However,
      there are no specific treatment guidelines for these patients. This may in part
      be because of the lack of high-quality evidence-based medicine in this therapy
      area. Many frequently prescribed medications were developed and licensed many
      years ago, in an era when clinical trial design was not expected to be as
      rigorous as it is today. CONCLUSION: This review highlights the need to conduct
      more high-quality clinical trials in patients with AE in order that specific
      guidelines for the management of this difficult proctological condition can be
      prepared.

PMID- 24898367
TI  - Syntheses, structures and flexible coordination of sterically demanding di- and
      "tri"-lithiated methandiides.
AB  - Lithiation of the sterically demanding bis(iminophosphoranyl)methane
      H2C{Ph2P(=NDip)}2 (Dip = 2,6-iPr2C6H3), H2L, with alkyllithium reagents afforded
      the methandiide complexes [(LLi2)2] 2, [LLi2(OEt2)2] 4, [LLi2(THF)3] 5,
      [LLi2(THF)2] 6, and [LLi2(PMDTA)] 7 (PMDTA = N,N,N',N'',N''
      pentamethyldiethylenetriamine), from various solvents or after the addition of
      donor molecules. The complex [HC(Ph2PNDip)(Ph2P)Li(THF)2] 3 was further
      identified as a by-product under certain conditions. Further lithiation of the
      methandiide in ortho-position of one P-bound phenyl group affords complexes of
      the trianionic ligand L'(3-), and the complexes [(L'Li3)2] 8 and [L'Li3(THF)4] 9
      were obtained. Different isomeric forms for the methandiide units investigated in
      solution and in the solid state are described, and the crystal structures of
      complexes 2, 3, and 5-9 are reported.

PMID- 24898368
TI  - The false classification of extinction risk in noisy environments.
AB  - Abundance trends are the basis for many classifications of threat and recovery
      status, but they can be a challenge to interpret because of observation error,
      stochastic variation in abundance (process noise) and temporal autocorrelation in
      that process noise. To measure the frequency of incorrectly detecting a decline
      (false-positive or false alarm) and failing to detect a true decline (false
      negative), we simulated stable and declining abundance time series across several
      magnitudes of observation error and autocorrelated process noise. We then
      empirically estimated the magnitude of observation error and autocorrelated
      process noise across a broad range of taxa and mapped these estimates onto the
      simulated parameter space. Based on the taxa we examined, at low classification
      thresholds (30% decline in abundance) and short observation windows (10 years),
      false alarms would be expected to occur, on average, about 40% of the time
      assuming density-independent dynamics, whereas false-negatives would be expected
      to occur about 60% of the time. However, false alarms and failures to detect true
      declines were reduced at higher classification thresholds (50% or 80% declines),
      longer observation windows (20, 40, 60 years), and assuming density-dependent
      dynamics. The lowest false-positive and false-negative rates are likely to occur
      for large-bodied, long-lived animal species. 

PMID- 24898370
TI  - Global late Quaternary megafauna extinctions linked to humans, not climate
      change.
AB  - The late Quaternary megafauna extinction was a severe global-scale event. Two
      factors, climate change and modern humans, have received broad support as the
      primary drivers, but their absolute and relative importance remains
      controversial. To date, focus has been on the extinction chronology of individual
      or small groups of species, specific geographical regions or macroscale studies
      at very coarse geographical and taxonomic resolution, limiting the possibility of
      adequately testing the proposed hypotheses. We present, to our knowledge, the
      first global analysis of this extinction based on comprehensive country-level
      data on the geographical distribution of all large mammal species (more than or
      equal to 10 kg) that have gone globally or continentally extinct between the
      beginning of the Last Interglacial at 132,000 years BP and the late Holocene 1000
      years BP, testing the relative roles played by glacial-interglacial climate
      change and humans. We show that the severity of extinction is strongly tied to
      hominin palaeobiogeography, with at most a weak, Eurasia-specific link to climate
      change. This first species-level macroscale analysis at relatively high
      geographical resolution provides strong support for modern humans as the primary
      driver of the worldwide megafauna losses during the late Quaternary.

PMID- 24898369
TI  - Trade-offs between and within scales: environmental persistence and within-host
      fitness of avian influenza viruses.
AB  - Trade-offs between different components of a pathogen's replication and
      transmission cycle are thought to be common. A number of studies have identified
      trade-offs that emerge across scales, reflecting the tension between strategies
      that optimize within-host proliferation and large-scale population spread. Most
      of these studies are theoretical in nature, with direct experimental tests of
      such cross-scale trade-offs still rare. Here, we report an analysis of avian
      influenza A viruses across scales, focusing on the phenotype of temperature
      dependent viral persistence. Taking advantage of a unique dataset that reports
      both environmental virus decay rates and strain-specific viral kinetics from duck
      challenge experiments, we show that the temperature-dependent environmental decay
      rate of a strain does not impact within-host virus load. Hence, for this
      phenotype, the scales of within-host infection dynamics and between-host
      environmental persistence do not seem to interact: viral fitness may be optimized
      on each scale without cross-scale trade-offs. Instead, we confirm the existence
      of a temperature-dependent persistence trade-off on a single scale, with some
      strains favouring environmental persistence in water at low temperatures while
      others reduce sensitivity to increasing temperatures. We show that this
      temperature-dependent trade-off is a robust phenomenon and does not depend on the
      details of data analysis. Our findings suggest that viruses might employ
      different environmental persistence strategies, which facilitates the coexistence
      of diverse strains in ecological niches. We conclude that a better understanding
      of the transmission and evolutionary dynamics of influenza A viruses probably
      requires empirical information regarding both within-host dynamics and
      environmental traits, integrated within a combined ecological and within-host
      framework. 

PMID- 24898371
TI  - Background level of risk determines how prey categorize predators and non
      predators.
AB  - Much of the plasticity that prey exhibit in response to predators is linked to
      the prey's immediate background level of risk. However, we know almost nothing of
      how background risk influences how prey learn to categorize predators and non
      predators. Learning non-predators probably represents one of the most
      underappreciated aspects of anti-predator decision-making. Here, we provide
      larval damselfish (Pomacentrus chrysurus) with a high or low background risk and
      then try to teach them to recognize a cue as non-threatening through the process
      of latent inhibition. Prey from the low-risk background that were pre-exposed to
      the novel odour cues in the absence of negative reinforcement for 3 days, and
      then provided the opportunity to learn to recognize the odour as threatening,
      failed to subsequently respond to the odour as a threat. Fish from the high-risk
      background showed a much different response. These fish did not learn the odour
      as non-threatening, probably because the cost of falsely learning an odour as non
      threatening is higher when the background level of risk is higher. Our work
      highlights that background level of risk appears to drive plasticity in cognition
      of prey animals learning to discriminate threats in their environment. 

PMID- 24898372
TI  - Novel biopesticide based on a spider venom peptide shows no adverse effects on
      honeybees.
AB  - Evidence is accumulating that commonly used pesticides are linked to decline of
      pollinator populations; adverse effects of three neonicotinoids on bees have led
      to bans on their use across the European Union. Developing insecticides that pose
      negligible risks to beneficial organisms such as honeybees is desirable and
      timely. One strategy is to use recombinant fusion proteins containing neuroactive
      peptides/proteins linked to a 'carrier' protein that confers oral toxicity.
      Hv1a/GNA (Galanthus nivalis agglutinin), containing an insect-specific spider
      venom calcium channel blocker (omega-hexatoxin-Hv1a) linked to snowdrop lectin
      (GNA) as a 'carrier', is an effective oral biopesticide towards various insect
      pests. Effects of Hv1a/GNA towards a non-target species, Apis mellifera, were
      assessed through a thorough early-tier risk assessment. Following feeding,
      honeybees internalized Hv1a/GNA, which reached the brain within 1 h after
      exposure. However, survival was only slightly affected by ingestion (LD50>100 ug
      bee(-1)) or injection of fusion protein. Bees fed acute (100 ug bee(-1)) or
      chronic (0.35 mg ml(-1)) doses of Hv1a/GNA and trained in an olfactory learning
      task had similar rates of learning and memory to no-pesticide controls. Larvae
      were unaffected, being able to degrade Hv1a/GNA. These tests suggest that
      Hv1a/GNA is unlikely to cause detrimental effects on honeybees, indicating that
      atracotoxins targeting calcium channels are potential alternatives to
      conventional pesticides.

PMID- 24898373
TI  - Trophic interactions of fish communities at midwater depths enhance long-term
      carbon storage and benthic production on continental slopes.
AB  - Biological transfer of nutrients and materials between linked ecosystems
      influences global carbon budgets and ecosystem structure and function.
      Identifying the organisms or functional groups that are responsible for nutrient
      transfer, and quantifying their influence on ecosystem structure and carbon
      capture is an essential step for informed management of ecosystems in physically
      distant, but ecologically linked areas. Here, we combine natural abundance stable
      isotope tracers and survey data to show that mid-water and bentho-pelagic-feeding
      demersal fishes play an important role in the ocean carbon cycle, bypassing the
      detrital particle flux and transferring carbon to deep long-term storage. Global
      peaks in biomass and diversity of fishes at mid-slope depths are explained by
      competitive release of the demersal fish predators of mid-water organisms, which
      in turn support benthic fish production. Over 50% of the biomass of the demersal
      fish community at depths between 500 and 1800 m is supported by biological rather
      than detrital nutrient flux processes, and we estimate that bentho-pelagic fishes
      from the UK-Irish continental slope capture and store a volume of carbon
      equivalent to over 1 million tonnes of CO2 every year.

PMID- 24898375
TI  - Do avian cooperative breeders live longer?
AB  - Cooperative breeding is not common in birds but intriguingly over-represented in
      several families, suggesting that predisposing factors, similar ecological
      constraints or a combination of the two facilitate the evolution of this breeding
      strategy. The life-history hypothesis proposes that cooperative breeding is
      facilitated by high annual survival, which increases the local population and
      leads to a shortage of breeding opportunities. Clutch size in cooperative
      breeders is also expected to be smaller. An earlier comparative analysis in a
      small sample of birds supported the hypothesis but this conclusion has been
      controversial. Here, I extend the analysis to a larger, worldwide sample and take
      into account potential confounding factors that may affect estimates of a slow
      pace of life and clutch size. In a sample of 81 species pairs consisting of
      closely related cooperative and non-cooperative breeders, I did not find an
      association between maximum longevity and cooperative breeding, controlling for
      diet, body mass and sampling effort. However, in a smaller sample of 37 pairs,
      adult annual survival was indeed higher in the cooperative breeders, controlling
      for body mass. There was no association between clutch size and cooperative
      breeding in a sample of 93 pairs. The results support the facilitating effect of
      high annual survival on the evolution of cooperative breeding in birds but the
      effect on clutch size remains elusive. 

PMID- 24898374
TI  - Untangling interactions: do temperature and habitat fragmentation gradients
      simultaneously impact biotic relationships?
AB  - Gaining insight into the impact of anthropogenic change on ecosystems requires
      investigation into interdependencies between multiple drivers of ecological
      change and multiple biotic responses. Global environmental change drivers can act
      simultaneously to impact the abundance and diversity of biota, but few studies
      have also measured the impact across trophic levels. We firstly investigated
      whether climate (using temperature differences across a latitudinal gradient as a
      surrogate) interacts with habitat fragmentation (measured according to fragment
      area and distance to habitat edges) to impact a New Zealand tri-trophic food
      chain (plant, herbivore and natural enemy). Secondly, we examined how these
      interactions might differentially impact both the density and biotic processes of
      species at each of the three trophic levels. We found evidence to suggest that
      these drivers act non-additively across trophic levels. The nature of these
      interactions however varied: location synergistically interacted with
      fragmentation measures to exacerbate the detrimental effects on consumer density;
      and antagonistically interacted to ameliorate the impact on plant density and on
      the interactions between trophic levels (herbivory and parasitoid attack rate).
      Our findings indicate that the ecological consequences of multiple global change
      drivers are strongly interactive and vary according to the trophic level studied
      and whether density or ecological processes are investigated.

PMID- 24898376
TI  - Social evolution of toxic metal bioremediation in Pseudomonas aeruginosa.
AB  - Bacteria are often iron-limited, and hence produce extracellular iron-scavenging
      siderophores. A crucial feature of siderophore production is that it can be an
      altruistic behaviour (individually costly but benefitting neighbouring cells),
      thus siderophore producers can be invaded by non-producing social 'cheats'.
      Recent studies have shown that siderophores can also bind other heavy metals
      (such as Cu and Zn), but in this case siderophore chelation actually reduces
      metal uptake by bacteria. These complexes reduce heavy metal toxicity, hence
      siderophore production may contribute to toxic metal bioremediation. Here, we
      show that siderophore production in the context of bioremediation is also an
      altruistic trait and can be exploited by cheating phenotypes in the opportunistic
      pathogen Pseudomonas aeruginosa. Specifically, we show that in toxic copper
      concentrations (i) siderophore non-producers evolve de novo and reach high
      frequencies, and (ii) producing strains are fitter than isogenic non-producing
      strains in monoculture, and vice versa in co-culture. Moreover, we show that the
      evolutionary effect copper has on reducing siderophore production is greater than
      the reduction observed under iron-limited conditions. We discuss the relevance of
      these results to the evolution of siderophore production in natural communities
      and heavy metal bioremediation. 

PMID- 24898377
TI  - MRI analysis of the ISOBAR TTL internal fixation system for the dynamic fixation
      of intervertebral discs: a comparison with rigid internal fixation.
AB  - OBJECTIVES: Using magnetic resonance imaging (MRI), we analyzed the efficacy of
      the posterior approach lumbar ISOBAR TTL internal fixation system for the dynamic
      fixation of intervertebral discs, with particular emphasis on its effects on
      degenerative intervertebral disc disease. METHODS: We retrospectively compared
      the MRIs of 54 patients who had previously undergone either rigid internal
      fixation of the lumbar spine or ISOBAR TTL dynamic fixation for the treatment of
      lumbar spondylolisthesis. All patients had received preoperative and 6-, 12-, and
      24-month postoperative MRI scans of the lumbar spine with acquisition of both
      routine and diffusion-weighted images (DWI). The upper-segment discs of the
      fusion were subjected to Pfirrmann grading, and the lumbar intervertebral discs
      in the DWI sagittal plane were manually drawn; the apparent diffusion coefficient
      (ADC) value was measured. RESULTS: ADC values in the ISOBAR TTL dynamic fixation
      group measured at the 6-, 12-, and 24-month postoperative MRI studies were
      increased compared to the preoperative ADC values. The ADC values in the ISOBAR
      TTL dynamic fixation group at 24 months postoperatively were significantly
      different from the preoperative values (P < 0.05). At 24 months, the
      postoperative ADC values were significantly different between the rigid fixation
      group and the ISOBAR TTL dynamic fixation group (P < 0.05). CONCLUSION: MRI
      imaging findings indicated that the posterior approach lumbar ISOBAR TTL internal
      fixation system can prevent or delay the degeneration of intervertebral discs.

PMID- 24898378
TI  - Are middle-age blood pressure levels related to color vision impairment? The
      Okubo Color Study.
AB  - BACKGROUND: We sought to investigate the association between blood pressure
      levels and prevalence of acquired color vision impairment in middle-aged Japanese
      men. METHODS: Participants underwent color vision testing, ophthalmological
      examination, standardized interview, physical record examination, and venous
      blood examination. Cardiovascular disease risk factors were determined based on
      blood and physical examination results and the interview. Logistic regression
      analysis was performed after adjusting for body mass index, systemic
      dyslipidemia, diabetes, cataract, glaucoma, smoking status, and drinking status.
      RESULTS: Of 1,042 men, 872 were eligible for the study, 130 failed the Lanthony
      15-hue desaturated panel (D-15 DS) diagnosed as acquired color vision impairment
      15-hue, and 31 failed the Farnsworth-Munsell 100-hue test diagnosed as acquired
      color vision impairment 100-hue. Diastolic blood pressure was significantly
      correlated with both acquired color vision impairment in 100-hue patients
      (adjusted odds ratio (OR) for 10-mm Hg increases = 1.42; 95% confidence interval
      (CI) = 1.00-2.02) and acquired color vision impairment in 15-hue patients
      (adjusted OR for 10-mm Hg increases = 1.25; 95% CI = 1.04-1.51). The multiple
      adjusted ORs for acquired color vision impairment 100-hue patients and acquired
      color vision impairment 15-hue patients were 7.13 (95% CI = 1.72-27.88) and 4.37
      (95% CI = 1.69-11.03), respectively, for the highest blood pressure category
      (systolic blood pressure >= 160 and diastolic blood pressure >= 100 mm Hg)
      compared with those for the lowest blood pressure category (systolic blood
      pressure <120 and diastolic blood pressure <80 mm Hg). Tests for trends were
      significant (P < 0.05) in both analyses. CONCLUSIONS: Hypertension in middle-aged
      men may negatively modify vision-associated neuronal function.

PMID- 24898379
TI  - Levels of office blood pressure and their operating characteristics for detecting
      masked hypertension based on ambulatory blood pressure monitoring.
AB  - BACKGROUND: Masked hypertension (MH)--nonelevated office blood pressure (BP) with
      elevated out-of-office BP average--conveys cardiovascular risk similar to or
      approaching sustained hypertension, making its detection of potential clinical
      importance. However, it may not be feasible or cost-effective to perform
      ambulatory BP monitoring (ABPM) on all patients with a nonelevated office BP.
      There likely exists a level of office BP below which ABPM is not warranted
      because the probability of MH is low. METHODS: We analyzed data from 294 adults
      aged >= 30 years not on BP-lowering medication with office BP <140/90 mm Hg, all
      of whom underwent 24-hour ABPM. We calculated sensitivity, false-positive rate,
      and likelihood ratios (LRs) for the range of office BP cutoffs from 110 to 138 mm
      Hg systolic and from 68 to 88 mm Hg diastolic for detecting MH. RESULTS: The
      systolic BP cutoff with the highest +LR for detecting MH (1.8) was 120 mm Hg, and
      the diastolic cutoff with the highest +LR (2.4) was 82 mm Hg. However, the
      systolic level of 120 mm Hg had a false-positive rate of 42%, and the diastolic
      level of 82 mm Hg had a sensitivity of only 39%. CONCLUSIONS: The cutoff of
      office BP with the best overall operating characteristics for diagnosing MH is
      approximately 120/82 mm Hg. However, this cutoff may have an unacceptably high
      false-positive rate. Clinical risk tools to identify patients with nonelevated
      office BP for whom ABPM should be considered will likely need to include factors
      in addition to office BP.

PMID- 24898380
TI  - A rabbit model of spontaneous thrombosis induced by lipopolysaccharide.
AB  - AIM: Inflammation plays a critical role in the development of atherosclerotic
      plaque, and lipopolysaccharide (LPS) is a potentially important source of
      inflammation. The aim of this study was to develop a rabbit model of spontaneous
      thrombosis mimicking the pathophysiological and morphological characteristics of
      atherosclerotic plaque in humans. METHODS: The rabbits were randomized into four
      groups: group A (n=10) received a normal diet; group B (n=10) received a regular
      diet and weekly LPS injections (1 MUg/kg, Escherichia coli); group C (n=15)
      received a cholesterol-enriched diet before and after sustaining a balloon injury
      to the right common carotid artery; and group D (n=15) was treated the same as
      group C in addition to receiving LPS injections. The morphological
      characteristics of the resulting lesions were evaluated using optical coherence
      tomography (OCT) and histology. RESULTS: No significant atherosclerotic plaque
      was observed in groups A or B. Group D exhibited a higher incidence of
      spontaneous luminal thrombi than group C or B (60% vs. 20% vs. 10%, p<0.05). All
      of the thrombi detected with OCT were confirmed on histology. A good correlation
      between the fibrous cap thickness and thrombus arc was obtained on OCT and the
      histological evaluations. CONCLUSIONS: A rabbit model of LPS-induced spontaneous
      thrombosis was developed in which OCT was used to follow changes in plaque
      morphology.

PMID- 24898381
TI  - A low serum free triiodothyronine level is associated with epicardial adipose
      tissue in peritoneal dialysis patients.
AB  - AIM: Cardiovascular disease is a major cause of mortality in dialysis patients.
      Epicardial adipose tissue (EAT) has been proposed as a cardiovascular risk marker
      in this population. Subclinical hypothyroidism and low free triiodothyronine
      (fT3) levels are associated with EAT in patients without chronic renal failure.
      The aim of this study was to investigate the relationship between EAT and low
      free T3 levels in peritoneal dialysis (PD) patients. METHODS: A total of 125
      prevalent PD patients were enrolled in this cross-sectional study. The epicardial
      fat thickness (EFT) was measured by echocardiography, and the endothelial
      function was assessed by flow mediated dilatation (FMD). Thyroid function tests
      were performed by an enzyme immunoassay. RESULTS: The mean age of the patients
      was 51 +/- 13, and the time on PD was 36 months. The mean EFT was 6.7 +/- 2.9 mm.
      The EFT correlated positively with the patient age, systolic blood pressure (BP),
      mean BP, high sensitivity C-reactive protein (hs-CRP) level and body mass index
      (BMI), and negatively with the fT3 level and FMD. The median fT3 value was 2.53,
      and patients were divided according to their serum fT3 values (within the normal
      range and below the reference level). Compared with patients in the low fT3
      group, the subjects in the normal fT3 group had higher serum albumin levels and
      FMD, but a lower BMI, plasma fasting glucose level, EFT, TSH level, hs-CRP level,
      low density lipoprotein (LDL) cholesterol level and mean BP in office
      measurements, and both the diastolic BP and mean BP by ambulatory blood pressure
      measurement. A multivariate linear regression analysis showed that the EFT was
      predicted by the hs-CRP and fT3 levels. CONCLUSION: Low free T3 levels are
      associated with the epicardial fat thickness in PD patients. Further studies are
      needed to evaluate the pathogenesis and to support these findings.

PMID- 24898382
TI  - An unusual follicular eruption in a young adult with new-onset type I diabetes
      mellitus.

PMID- 24898383
TI  - Theory of non-equilibrium critical phenomena in three-dimensional condensed
      systems of charged mobile nanoparticles.
AB  - A study of 3d electrostatic self-assembly (SA) in systems of charged
      nanoparticles (NPs) is one of the most difficult theoretical problems. In
      particular, the limiting case of negligible or very low polar media (e.g. salt)
      concentration, where the long-range NP interactions cannot be reduced to commonly
      used effective short-range (Yukawa) potentials, remains unstudied. Moreover, the
      present study has demonstrated that unlike the Debye-Huckel theory, a complete
      screening of the charges in SA kinetics (dynamic SA) is not always possible.
      Generally speaking, one has to take into account implicitly how each NP interacts
      with all other NPs (the true long-range interactions). Traditional theoretical
      methods allow us to monitor such electrostatic 3d system kinetics only for very
      short times, which is far from sufficient for understanding the dynamic SA. In
      this paper, combining an integrated analytical approach (the non-linear integro
      differential kinetic equation for correlation functions) and reverse Monte Carlo
      in the 3d case, we have obtained a self-consistent solution of this challenging
      problem. We demonstrate, in particular, the existence of critical points and
      critical phenomena in the non-equilibrium kinetics in a 3d system of oppositely
      charged mobile NPs. 

PMID- 24898385
TI  - Microbial dynamics during and after in situ chemical oxidation of chlorinated
      solvents.
AB  - In situ chemical oxidation (ISCO) followed by a bioremediation step is
      increasingly being considered as an effective biphasic technology. Information on
      the impact of chemical oxidants on organohalide respiring bacteria (OHRB),
      however, is largely lacking. Therefore, we used quantitative PCR (qPCR) to
      monitor the abundance of OHRB (Dehalococcoides mccartyi, Dehalobacter, Geobacter,
      and Desulfitobacterium) and reductive dehalogenase genes (rdh; tceA, vcrA, and
      bvcA) at a field location contaminated with chlorinated solvents prior to and
      following treatment with sodium persulfate. Natural attenuation of the
      contaminants tetrachloroethene (PCE) and trichloroethene (TCE) observed prior to
      ISCO was confirmed by the distribution of OHRB and rdh genes. In wells impacted
      by persulfate treatment, a 1 to 3 order of magnitude reduction in the abundances
      of OHRB and complete absence of rdh genes was observed 21 days after ISCO.
      Groundwater acidification (pH<3) and increase in the oxidation reduction
      potential (>500 mV) due to persulfate treatment were significant and contributed
      to disruption of the microbial community. In wells only mildly impacted by
      persulfate, a slight stimulation of the microbial community was observed, with
      more than 1 order of magnitude increase in the abundance of Geobacter and
      Desulfitobacterium 36 days after ISCO. After six months, regeneration of the OHRB
      community occurred, however, neither D. mccartyi nor any rdh genes were observed,
      indicating extended disruption of biological natural attenuation (NA) capacity
      following persulfate treatment. For full restoration of biological NA activity,
      additional time may prove sufficient; otherwise addition electron donor amendment
      or bioaugmentation may be required. 

PMID- 24898386
TI  - Enhanced LPS-induced peritonitis in mice deficiency of cullin 4B in macrophages.
AB  - Cullin 4B (CUL4B), a member of the cullin protein family, is a scaffold protein
      of the CUL4B-RING-E3 ligase complex that ubiquitinates intracellular
      proteins.CUL4B's targets include cell cycle-regulated proteins and DNA
      replication-related molecules. In this study, we generated myeloid-specific Cul4b
      deficient mice (Cul4b(f/y);LysM-Cre(KI/KI)) to investigate the influence of Cul4b
      deficiency on innate immunity, especially on the function of macrophages. Our
      results show that an intraperitoneal injection of lipopolysaccharide (LPS) led to
      a significant decrease in body weights and increased leukocyte infiltrates with
      increased chemokines in the peritoneal cavity of Cul4b(f/y);LysM-Cre(KI/KI) mice.
      However, the proinflammatory cytokines, IL-6 and TNF-alpha did not increase in
      LPS-injected Cul4b(f/y);LysM-Cre(KI/KI) mice. Furthermore, bone marrow-derived
      macrophages from Cul4b(f/y);LysM-Cre(KI/KI) mice secreted higher levels of
      chemokines but lower levels of TNF-alpha and IL-6 upon LPS stimulation. Of note,
      increased proliferation of Cul4b-deficient macrophages was also observed. These
      results show that myeloid-specific Cul4b deficiency worsens LPS-induced
      peritonitis. In addition, Cul4b deficiency leads to enhanced DNA replication and
      proliferation, increased production of chemokines but a decreased production of
      proinflammatory cytokines of macrophages. Our data highlight a new role of cullin
      family, CUL4B, in the immune system. 

PMID- 24898387
TI  - Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and
      pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia.
AB  - We analyzed two West African samples (Guinea-Bissau: n=289 cases and 322
      controls; The Gambia: n=240 cases and 248 controls) to evaluate single-nucleotide
      polymorphisms (SNPs) in Epiregulin (EREG) and V-ATPase (T-cell immune regulator 1
      (TCIRG1)) using single and multilocus analyses to determine whether previously
      described associations with pulmonary tuberculosis (PTB) in Vietnamese and
      Italians would replicate in African populations. We did not detect any
      significant single locus or haplotype associations in either sample. We also
      performed exploratory pairwise interaction analyses using Visualization of
      Statistical Epistasis Networks (ViSEN), a novel method to detect only
      interactions among multiple variables, to elucidate possible interaction effects
      between SNPs and demographic factors. Although we found no strong evidence of
      marginal effects, there were several significant pairwise interactions that were
      identified in either the Guinea-Bissau or the Gambian samples, two of which
      replicated across populations. Our results indicate that the effects of EREG and
      TCIRG1 variants on PTB susceptibility, to the extent that they exist, are
      dependent on gene-gene interactions in West African populations as detected with
      ViSEN. In addition, epistatic effects are likely to be influenced by inter- and
      intra-population differences in genetic or environmental context and/or the
      mycobacterial lineages causing disease. 

PMID- 24898388
TI  - Genotype CC of rs12979860 is providing protection against infection rather than
      assisting in treatment response for HCV genotype 3a infection.
AB  - Recent discovery of single-nucleotide polymorphisms located in the upstream
      region of interleukin-28B (IL28B) has shown association with interferon (IFN)
      treatment response especially in hepatitis C virus (HCV) genotype 1-infected
      patients. Pakistan, being the country with second highest prevalence of HCV with
      predominantly 3a genotype infection, bears a significant disease burden. The
      present study was conducted to evaluate the effect of rs12979860 genotypes on
      treatment response in HCV-3a-infected patients. This study shows that the CC
      genotype is providing protection against infection to HCV. But once infected, the
      CC genotype patients show viral persistence following IFN therapy. The TT
      genotype is assisting the 3a patients in viral clearance after IFN treatment. To
      our knowledge, this is the first study showing rs12979860 genotype association
      with IFN response in Pakistani HCV-3a-infected patients. 

PMID- 24898390
TI  - Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by
      microglia.
AB  - The removal of dying neurons by microglia has a key role during both development
      and in several diseases. To date, little is known about the cellular and
      molecular processes underlying neuronal engulfment in the brain. Here we took a
      live imaging approach to quantify neuronal cell death progression in embryonic
      zebrafish brains and studied the response of microglia. We show that microglia
      engulf dying neurons by extending cellular branches that form phagosomes at their
      tips. At the molecular level we found that microglia lacking the
      phosphatidylserine receptors BAI1 and TIM-4, are able to recognize the apoptotic
      targets but display distinct clearance defects. Indeed, BAI1 controls the
      formation of phagosomes around dying neurons and cargo transport, whereas TIM-4
      is required for phagosome stabilization. Using this single-cell resolution
      approach we established that it is the combined activity of BAI1 and TIM-4 that
      allows microglia to remove dying neurons. 

PMID- 24898389
TI  - IL-12 is required for mTOR regulation of memory CTLs during viral infection.
AB  - The induction of functional memory cytotoxic T lymphocytes (CTLs) is a major goal
      of vaccination against intracellular pathogens. Interleukin (IL)-12 is critical
      for the generation of memory CTLs, and inhibition of mammalian target of
      rapamycin (mTOR) by rapamycin can effectively enhance the memory CTL response.
      Yet, the role of IL-12 in mTOR's regulation of memory CTL is unknown. Here we
      hypothesized that the immunostimulatory effects of mTOR on memory CTLs requires
      IL-12 signaling. Our results revealed that rapamycin increased the generation of
      memory CTLs in vaccinia virus infection, and this enhancement was dependent upon
      the IL-12 signal. Furthermore, IL-12 receptor deficiency diminished the secondary
      expansion of rapamycin-regulated memory and resultant secondary memory CTLs were
      abolished. Rapamycin enhanced IL-12 signaling by upregulating IL-12 receptor
      beta2 expression and signal transducer and activator of transcription factor 4
      phosphorylation in CTLs during early infection. In addition, rapamycin
      continually suppressed T-bet expression in both wild-type and IL-12 receptor
      knockout CTLs. These results indicate an essential role for IL-12 in the
      regulation of memory CTLs by mTOR and highlight the importance of considering the
      interplay between cytokines and adjuvants during vaccine design. 

PMID- 24898392
TI  - The complex Chiari malformation: an evolution of understanding.

PMID- 24898391
TI  - Reconstruction of focal cartilage defects in the talus with miniarthrotomy and
      collagen matrix.
AB  - SURGICAL PRINCIPAL AND OBJECTIVE: Treatment of focal cartilage defects (traumatic
      or osteochondrosis dissecans) of the talus using a collagen matrix. The goal is
      to stabilize the superclot formed after microfracturing to accommodate cartilage
      repair. The procedure can be carried out via miniarthrotomy, without medial
      malleolus osteotomy. INDICATIONS: International Cartilage Repair Society (ICRS)
      grade III and IV focal cartilage defects of the talus > 1.5 cm(2).
      CONTRAINDICATIONS: Generalized osteoarthritis, inflammatory joint disease, gout,
      neuroarthropathy. SURGICAL TECHNIQUE: Miniarthrotomy to open the ankle joint.
      Debridement of unstable cartilage and necrotic bone, curettage of cysts. Filling
      of the bone defects with autologous cancellous bone. Sealing of reconstructed
      bone with fibrin glue and attachment of a collagen matrix shaped to precisely fit
      the defect. POSTOPERATIVE REGIMEN: Immobilization for 48 h. Partial weight
      bearing of 10 kg for 6 weeks, with continuous passive motion. Increasing weight
      bearing from 7 weeks onwards. RESULTS: Follow-up of at least 30 months in 14
      patients showed improvement in the Score of the American Orthopedic Foot and
      Ankle Society (AOFAS) from 50 to 89 points, with equal mobility on both sides of
      the upper ankle joint.

PMID- 24898393
TI  - Magnetic resonance imaging features of complex Chiari malformation variant of
      Chiari 1 malformation.
AB  - BACKGROUND: Complex Chiari malformation is a subgroup of Chiari 1 malformation
      with distinct imaging features. Children with complex Chiari malformation are
      reported to have a more severe clinical phenotype and sometimes require more
      extensive surgical treatment than those with uncomplicated Chiari 1 malformation.
      OBJECTIVE: We describe reported MR imaging features of complex Chiari
      malformation and evaluate the utility of craniometric parameters and qualitative
      anatomical observations for distinguishing complex Chiari malformation from
      uncomplicated Chiari 1 malformation. MATERIALS AND METHODS: We conducted a
      retrospective search of the institutional imaging database using the keywords
      "Chiari" and "Chiari 1" to identify children imaged during the 2006-2011 time
      period. Children with Chiari 2 malformation were excluded after imaging review.
      We used the first available diagnostic brain or cervical spine MR study for data
      measurement. Standard measurements and observations were made of obex level (mm),
      cerebellar tonsillar descent (mm), perpendicular distance to basion-C2 line (pB
      C2, mm), craniocervical angle (degrees), clivus length, and presence or absence
      of syringohydromyelia, basilar invagination and congenital craniovertebral
      junction osseous anomalies. After imaging review, we accessed the institutional
      health care clinical database to determine whether each subject clinically met
      criteria for Chiari 1 malformation or complex Chiari malformation. RESULTS: Obex
      level and craniocervical angle measurements showed statistically significant
      differences between the populations with complex Chiari malformation and
      uncomplicated Chiari 1 malformation. Cerebellar tonsillar descent and
      perpendicular distance to basion-C2 line measurements trended toward but did not
      meet statistical significance. Odontoid retroflexion, craniovertebral junction
      osseous anomalies, and syringohydromyelia were all observed proportionally more
      often in children with complex Chiari malformation than in those with Chiari 1
      malformation. CONCLUSION: Characteristic imaging features of complex Chiari
      malformation, especially obex level, permit its distinction from the more common
      uncomplicated Chiari 1 malformation.

PMID- 24898395
TI  - The metaphyseal collar is also present until later childhood and at birth.

PMID- 24898394
TI  - Imaging of pediatric pathology during the Iraq and Afghanistan conflicts.
AB  - United States Armed Forces radiologists deployed to Afghanistan and Iraq in
      modern military conflicts may encounter pediatric patients as a casualty of war
      or when providing humanitarian assistance to the indigenous population. Pediatric
      patients account for 4-7% of admissions at U.S. military hospitals during the
      Iraq and Afghanistan conflicts. It is pertinent for radiologists in the
      humanitarian care team to be familiar with imaging pediatric trauma patients, the
      pathology endemic to the local population, and delayed presentations of
      congenital and developmental disorders to adequately care for these patients. The
      radiological manifestations of various pediatric disorders seen in the setting of
      the Iraq and Afghanistan conflicts will be explored. 

PMID- 24898396
TI  - Reply to Dr. Oestreich's letter regarding the metaphyseal collar.

PMID- 24898397
TI  - Effect of autophagy inhibition on cell viability and cell cycle progression in
      MDA-MB-231 human breast cancer cells.
AB  - Atg7 is an autophagy-related gene, and is involved in two ubiquitin-like
      conjugation systems in the process of autophagy. It is well established that 3
      methyladenine (3Ma) is an autophagy inhibitor. The present study aimed to
      investigate the effect of autophagy inhibition on the cell viability and cell
      cycle progression of human breast cancer cells. MDA-MB-231 human breast cancer
      cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with high
      glucose, then divided into six groups. The six groups included the three
      fundamental groups as follows: The control group (untreated); the starvation
      group (high-glucose DMEM replaced with glucose-free minimal essential medium);
      and the starvation 3Ma group (maintained in glucose-free culture medium and
      treated with the autophagy inhibitor 3Ma). The three fundamental groups were
      further divided into Atg7 siRNA-transfected and non-transfected groups. The cell
      viability and apoptosis of each group was determined by MTT assay and flow
      cytometry. The results of the current study demonstrated that Atg7 deficiency
      alone had no statically significant effect on the cell viability of MDA-MB-231
      human breast cancer cells, while 3Ma reduced the cell viability and its effect
      was potentiated by Atg7 deficiency. Atg7 deficiency was more intense than 3Ma in
      the promotion of apoptosis and cell arrest in G0/G1-phase in the absence of
      glucose and its effect was reduced by 3Ma. In conclusion, 3Ma and Atg7 may be
      involved in different pathways in the process of autophagy. Inhibition of
      autophagy may influence the cell viability and cell cycle through different
      pathways in MDA-MB-231 human breast cancer cells. 

PMID- 24898398
TI  - Photoplethysmographic signals to predict the success of lumbar sympathetic
      blockade for lower extremity pain.
AB  - OBJECTIVE: A prospective, observational study to investigate how
      photoplethysmography (PPG) signals change during lumbar sympathetic blockade
      (LSB), and whether these changes can predict sympathetically mediated pain (SMP).
      METHODS: Patients with unilateral lower extremity pain and self-reported cold
      hyperalgesia underwent LSB. Bilateral temperature and PPG signals (AC and DC)
      were recorded. Power spectrum analysis (PSA) was performed. RESULTS: Of the total
      patient cohort (n = 38), eight patients (22.1%) had excellent pain-relief after
      LSB and were determined to have SMP. In all patients, the PPG AC signal changed
      immediately after drug administration, before any temperature change. DC signals
      decreased slowly in a linear fashion. PSA of DC signals showed significantly
      lower low-frequency/high-frequency (LF/HF) ratios in the SMP group than the
      sympathetically independent pain group, both before and after LSB. A cut-off
      value of 2.92 for LF/HF resulted in sensitivity, specificity and positive
      predictive values for SMP of 75.0%, 76.7% and 3.21 [1.5, 6.9], respectively.
      CONCLUSIONS: PPG may be used as an early indicator of a successful LSB and could
      also be helpful in diagnosing SMP.

PMID- 24898399
TI  - Resting-state brain activation correlates with short-time antidepressant
      treatment outcome in drug-naive patients with major depressive disorder.
AB  - OBJECTIVE: A resting-state functional magnetic resonance imaging study (fMRI) to
      investigate pretreatment regional differences in brain function, in patients with
      early treatment responsive (ERD) and early treatment nonresponsive (END) major
      depressive disorder (MDD). METHODS: Patients with MDD and healthy control
      subjects underwent fMRI. Intrinsic neural activity at baseline was evaluated via
      amplitude of low-frequency fluctuations (ALFF). Antidepressant treatment was
      initiated after MRI. All patients received selective serotonin reuptake inhibitor
      type antidepressants at the minimum effective dose. RESULTS: There were
      significant differences in brain activity between patients (n = 56) and control
      subjects (n = 33). Brain activity in patients with ERD (n = 26) differed from
      those with END (n = 30) in the lingual gyrus and cerebellum. There was a
      significantly correlation between activity in these regions and disease duration
      in patients with ERD, and with amelioration of depressive symptoms in patients
      with END. CONCLUSIONS: Brain regions related to the neural mechanism of MDD early
      treatment outcome were identified. These regions may have important implications
      for the treatment of MDD.

PMID- 24898400
TI  - Irradiation enhances expression of cxcr4 in murine glioma cells via HIF-1alpha
      independent pathway.
AB  - OBJECTIVE: To investigate levels of chemokine (C-X-C motif) receptor 4 (cxcr4)
      mRNA and protein in X-irradiated glioma cells. METHODS: Murine malignant glioma
      GL261 cells transfected with hypoxia-inducible factor (HIF)-1alpha miRNA or
      control miRNA were irradiated with X-radiation. Cxcr4 mRNA and protein were
      analysed using real-time reverse transcription-polymerase chain reaction and
      Western blot, respectively. RESULTS: Levels of cxcr4 protein in GL261 cells
      increased in a radiation dose-dependent manner 48 h after 0, 5, 10 and 15 Gy X
      irradiation. Irradiation of both HIF-1alpha knockdown cells and control cells
      resulted in a significant increase in cxcr4 mRNA levels, compared with
      nonirradiated cells, at 24 h after 5 Gy X-irradiation. CONCLUSION: Irradiation
      enhances expression of cxcr4 in glioma cells via a HIF-1alpha-independent
      pathway.

PMID- 24898401
TI  - Reply to: Comparative analysis of GATA3 mutation profiles between Asian and
      Western patients with breast cancer. Is there really a difference?

PMID- 24898403
TI  - Dietitians' perceptions of communicating with preadolescent, overweight children
      in the consultation setting: the potential for e-resources.
AB  - BACKGROUND: There are calls to enhance existing child weight management
      interventions and to develop new treatment approaches. The potential for
      interactive electronic resources (e-resources) to support child-dietitian
      communication has yet to be explored. Towards developing such a tool, the present
      study aimed to understand dietetic attitudes and approaches to communicating with
      preadolescent overweight children in individual consultations to support
      behaviour change. METHODS: A purposive sample of 18 dietitians, providing weight
      management advice to overweight 7-11-year-old children, took part in the study.
      Individual semi-structured telephone interviews were conducted. Data were
      transcribed and then analysed using inductive thematic analysis. Content analysis
      was used to interpret dietetic attitude towards e-resources. RESULTS: Six
      overarching themes were identified describing dietitians' views: the complexity
      of treating childhood obesity, the strategic balance of dietetic communication
      focus between child and parent, the child's capacity to communicate affecting
      their contribution, dietetic approaches to verbal child communication and the
      features of resources that can support them, as well as dietetic expectations for
      resources. Independent inter-rater agreement for the themes was 76.9% and 73.1%,
      respectively. The majority of dietitians (n = 13) supported the concept of
      introducing an interactive multimedia e-resource into child weight management
      consultations. CONCLUSIONS: Most dietitians sought to engage the preadolescent
      child in the consultation, using dietetic visual aids to complement verbal
      strategies and to serve as scaffolding for the conversation. There is scope for
      interactive e-resources to enhance communication, provided that they are flexibly
      tailored to meet the needs of the dietitian and the overweight child.

PMID- 24898402
TI  - Orexin A attenuates the sleep-promoting effect of adenosine in the lateral
      hypothalamus of rats.
AB  - Orexin neurons within the lateral hypothalamus play a crucial role in the
      promotion and maintenance of arousal. Studies have strongly suggested that orexin
      neurons are an important target in endogenous adenosine-regulated sleep
      homeostasis. Orexin A induces a robust increase in the firing activity of orexin
      neurons, while adenosine has an inhibitory effect. Whether the excitatory action
      of orexins in the lateral hypothalamus actually promotes wakefulness and reverses
      the sleep-producing effect of adenosine in vivo is less clear. In this study,
      electroencephalographic and electromyographic recordings were used to investigate
      the effects of orexin A and adenosine on sleep and wakefulness in rats. We found
      that microinjection of orexin A into the lateral hypothalamus increased
      wakefulness with a concomitant reduction of sleep during the first 3 h of post
      injection recording, and this was completely blocked by a selective antagonist
      for orexin receptor 1, SB 334867. The enhancement of wakefulness also occurred
      after application of the excitatory neurotransmitter glutamate in the first 3 h
      post-injection. However, in the presence of the NMDA receptor antagonist APV,
      orexin A did not induce any change of sleep and wakefulness in the first 3 h.
      Further, exogenous application of adenosine into the lateral hypothalamus induced
      a marked increase of sleep in the first 3-h post-injection. No significant change
      in sleep and wakefulness was detected after adenosine application followed by
      orexin A administration into the same brain area. These findings suggest that the
      sleep-promoting action of adenosine can be reversed by orexin A applied to the
      lateral hypothalamus, perhaps by exciting glutamatergic input to orexin neurons
      via the action of orexin receptor 1.

PMID- 24898404
TI  - Thermotropic luminescent clustomesogen showing a nematic phase: a combination of
      experimental and molecular simulation studies.
AB  - Octahedral Mo6 nanoclusters are functionalized with two organic ligands
      containing cyanobiphenyl (CB) units, giving luminescent hybrid liquid crystals
      (LC). Although the mesogenic density around the bulky inorganic core is constant,
      the two hybrids show different LC properties. Interestingly, one of them shows a
      nematic phase, which is particularly rare for this kind of supermolecular system.
      This surprising result is explained by using large-scale molecular dynamic
      simulations. 

PMID- 24898405
TI  - Simultaneous determination and pharmacokinetic study of three isoflavones from
      Trifolium pratense extract in rat plasma by LC-MS/MS.
AB  - A highly selective and sensitive liquid chromatography-tandem mass spectrometry
      has been developed and validated for simultaneous determination of three
      isoflavones - ononin, formononetin and biochanin A - in rat plasma using
      lysionotin as internal standard (IS). The plasma samples were pretreated and
      extracted by liquid-liquid extraction. Chromatographic separation was
      accomplished on a C18 column with the column temperature of 30  degrees C and a
      mobile phase of methanol-0.1% formic acid (75:25, v/v). The detection was
      accomplished by multiple-reaction monitoring scanning with positive/negative ion
      switching electrospray ionization mode. The optimized mass transition ion pairs
      (m/z) for quantitation were 431.3/269.1 for ononin, 267.1/252.2 for formononetin,
      283.2/268.2 for biochanin A and 343.2/313.3 for IS. The total run time was 8.0
      min. Full validation of the assay was implemented, including selectivity,
      sensitivity, linearity, precision, accuracy, recovery, matrix effect and
      stability. This is the first report on simultaneous determination of the three
      major isoflavones in rat plasma after intragastric administration of Trifolium
      pratense extract. The results provided a significant basis for the clinical
      application of this herb Trifolium pratense.

PMID- 24898406
TI  - Optical coordinate tracking system using afocal optics for image-guided surgery.
AB  - PURPOSE: Image-guided surgery using medical robots supports surgeons by providing
      critical real-time feedback information, such as surgical instrument tracking,
      patient-specific models, and the use of surgery robots. An image-guided surgery
      system based on afocal optics was developed to overcome the problems associated
      with conventional optical tracking systems. METHOD: An optical tracking system
      was developed that utilizes afocal optics. Instead of using geometrically
      specified marker spheres as tracking targets, the proposed system uses a marker
      with a lens and a micro-engraved data-coded pattern. A position and orientation
      tracking algorithm was developed to utilize the observed afocal images of the
      marker patterns. The marker used in this tracking system can be manufactured in a
      smaller size than traditional optical tracker markers, and the accuracy of the
      proposed tracking system has significant potential for improvement due to its
      focused and highly magnified image. The system was tested in vitro on an optical
      bench with position and orientation measurement experiments using a commercial
      optical tracker, Polaris Vicra (NDI Corp.) for comparison. RESULTS: The afocal
      optical system provided accuracy in position and orientation that was equal or
      better than a commercial optical tracker system, and provided a high degree of
      consistency during in vitro testing. The position error was 21MU m, and the
      orientation error was 0.093 degrees . CONCLUSION: An afocal optical tracker is
      feasible and potentially advantageous for surgical navigation, as it is expected
      to have fewer occlusions and provide greater efficiency for coordinate matching
      and tracking of patient-specific models, surgical instruments, and surgery
      robots. This promising new system requires in vivo testing.

PMID- 24898408
TI  - Diffuse large B cell lymphoma presenting as a peri-anal abscess.
AB  - A non-healing peri-anal abscess can be difficult to manage and is often
      attributed to chronic disease. This case documents a male in his seventh decade
      who presented with multiple peri-anal collections. The abscess cavity had caused
      necrosis of the internal sphincter muscles resulting in faecal incontinence.
      Biopsies were conclusive for diffuse large B-cell lymphoma. A de-functioning
      colostomy was performed and the patient was initiated on CHOP-R chemotherapy.
      Anal lymphoma masquerading as a peri-anal abscess is rare. A high degree of
      suspicion must be maintained for an anal abscess which does not resolve with
      conservative management. 

PMID- 24898409
TI  - Epithelioid hemangioendothelioma encasing the left brachiocephalic vein.
AB  - Epithelioid hemangioendotheliomas are rare vascular tumors, often arising from
      medium to large veins in the extremities. Symptoms of these tumors vary depending
      upon location. Rarely, tumors may arise in chest and involve large vessels in the
      mediastinum. We present a case of a 17-year-old male presenting with compressive
      symptoms of the left upper extremity who was found to have a large epithelioid
      hemangioendothelioma encasing the left brachiocephalic vein. 

PMID- 24898407
TI  - Humid heat exposure induced oxidative stress and apoptosis in cardiomyocytes
      through the angiotensin II signaling pathway.
AB  - Exposure to humid heat stress leads to the initiation of serious physiological
      dysfunction that may result in heat-related diseases, including heat stroke, heat
      cramp, heat exhaustion, and even death. Increasing evidences have shown that the
      humid heat stress-induced dysfunction of the cardiovascular system was
      accompanied with severe cardiomyocyte injury; however, the precise mechanism of
      heat stress-induced injury of cardiomyocyte remains unknown. In the present
      study, we hypothesized that humid heat stress promoted oxidative stress through
      the activation of angiotensin II (Ang II) in cardiomyocytes. To test our
      hypothesis, we established mouse models of humid heat stress. Using the animal
      models, we found that Ang II levels in serum were significantly up-regulated and
      that the Ang II receptor AT1 was increased in cardiomyocytes. The antioxidant
      ability in plasma and heart tissues which was detected by the ferric
      reducing/antioxidant power assay was also decreased with the increased ROS
      production under humid heat stress, as was the expression of antioxidant genes
      (SOD2, HO-1, GPx). Furthermore, we demonstrated that the Ang II receptor
      antagonist, valsartan, effectively relieved oxidative stress, blocked Ang II
      signaling pathway and suppressed cardiomyocyte apoptosis induced by humid heat
      stress. In addition, overexpression of antioxidant genes reversed cardiomyocyte
      apoptosis induced by Ang II. Overall, these results implied that humid heat
      stress increased oxidative stress and caused apoptosis of cardiomyocytes through
      the Ang II signaling pathway. Thus, targeting the Ang II signaling pathway may
      provide a promising approach for the prevention and treatment of cardiovascular
      diseases caused by humid heat stress. 

PMID- 24898410
TI  - True idiopathic saccular aneurysm of the radial artery.
AB  - True aneurysms of hand arteries are rare. I present a case of a true saccular
      aneurysm of the distal radial artery in a 65-year-old woman with no history of
      trauma. The CT angiography, intraoperative features, operative procedure,
      histopathological examination and literature review are presented and discussed. 

PMID- 24898411
TI  - The regulatory landscape of osteogenic differentiation.
AB  - Differentiation of osteoblasts from mesenchymal stem cells (MSCs) is an integral
      part of bone development and homeostasis, and may when improperly regulated cause
      disease such as bone cancer or osteoporosis. Using unbiased high-throughput
      methods we here characterize the landscape of global changes in gene expression,
      histone modifications, and DNA methylation upon differentiation of human MSCs to
      the osteogenic lineage. Furthermore, we provide a first genome-wide
      characterization of DNA binding sites of the bone master regulatory transcription
      factor Runt-related transcription factor 2 (RUNX2) in human osteoblasts,
      revealing target genes associated with regulation of proliferation, migration,
      apoptosis, and with a significant overlap with p53 regulated genes. These
      findings expand on emerging evidence of a role for RUNX2 in cancer, including
      bone metastases, and the p53 regulatory network. We further demonstrate that
      RUNX2 binds to distant regulatory elements, promoters, and with high frequency to
      gene 3' ends. Finally, we identify TEAD2 and GTF2I as novel regulators of
      osteogenesis.

PMID- 24898412
TI  - Active avoidance from a crude oil soluble fraction by an Andean paramo copepod.
AB  - Several oil spills due to ruptures in the pipeline oil systems have occurred at
      the Andean paramo. A sample of this crude oil was mixed with water from a nearby
      Andean lagoon and the toxicity of the soluble fraction was assessed through
      lethal and avoidance assays with a locally occurring copepod (Boeckella
      occidentalis intermedia). The integration of mortality and avoidance aimed at
      predicting the immediate decline of copepod populations facing an oil leakage.
      The 24-h median lethal PAH concentration was 42.7 (26.4-91.6) ug L(-1). In the 12
      h avoidance assay, 30% avoidance was recorded at the highest PAH concentration
      (19.4 ug L(-1)). The mortality at this PAH concentration would be of 25% and,
      thus, the population immediate decline would be of 55%. The inclusion of non
      forced exposure testing with the quantification of the avoidance response in
      environmental risk assessments is, therefore, supported due to underestimation of
      the lethal assays.

PMID- 24898413
TI  - Nanobiotechnology promotes noninvasive high-intensity focused ultrasound cancer
      surgery.
AB  - The successful cancer eradication in a noninvasive manner is the ultimate
      objective in the fight against cancer. As a "bloodless scalpel," high-intensity
      focused ultrasound (HIFU) is regarded as one of the most promising and
      representative noninvasive therapeutic modalities for cancer surgery. However,
      large-scale clinical applications of HIFU are still in their infancy because of
      critical efficiency and safety issues which remain to be solved. Fortunately,
      recently developed nanobiotechnology provides an alternative efficient approach
      to improve such important issues in HIFU, especially for cancer therapy. This
      Research News presents the very recent exciting progresses on the elaborate
      design and fabrication of organic, inorganic, and organic/inorganic hybrid
      nanoparticles for enhancing the HIFU ablation efficiency against tumor tissues.
      It is highly expected that this Research News can arouse more extensive research
      enthusiasm on the development of functional nanomaterials for highly efficient
      HIFU-based synergistic therapy, which will give a promising noninvasive
      therapeutic modality for the successful cancer therapy with minimal damage to
      surrounding normal tissues, due to the noninvasive and site-specific therapeutic
      features of HIFU. 

PMID- 24898415
TI  - Structure and optical properties of (CdSxSe(1-x))42 nanoclusters.
AB  - The structures of the (CdS)42, (CdSe)42, Cd42Se32S10, Cd42Se22S20, and
      Cd42Se10S32 clusters have been determined using the simulated annealing method.
      Factors influencing the band gap value have been analysed. We show that the gap
      is most significantly reduced when strongly under coordinated atoms are present
      on the surface of the nanoclusters. In addition, the band gap depends on the S
      concentration as well as on the distribution of the S and Se atoms in the
      clusters. We present the optical absorption spectra calculated with BSE and RPA
      methods based on the GW corrected quasiparticle energies. Strong electron-hole
      coupling is observed for all the clusters, shifting the calculated RPA onset of
      optical absorption to lower energies. The absorption edge is shifted to higher
      photon energies as S concentration increases. The calculated energy separation of
      the first bright exciton and first dark exciton increases with S concentration. 

PMID- 24898414
TI  - Preterm delivery as a predictor of diurnal cortisol profiles in adulthood:
      evidence from Cebu, Philippines.
AB  - OBJECTIVES: Fetal exposure to elevated maternal cortisol can permanently modify
      hypothalamic-pituitary-adrenal (HPA) axis function, and thereby have long-term
      health impacts. Maternal cortisol steadily increases throughout normal pregnancy,
      but is abnormally high in preterm deliveries (<37 weeks). Prematurity remains a
      widespread public health problem, yet little is known about its potential long
      term effects on adult HPA function. Here we test the hypothesis that diurnal
      cortisol profiles measured in young adulthood will vary based upon an
      individual's preterm status. METHODS: Diurnal salivary cortisol profiles, a
      marker of HPA-axis function, were measured in 1,403 young adults (ages 21-23
      years) participating in the Cebu Longitudinal Health and Nutrition Survey,
      located in Metropolitan Cebu City, Philippines. RESULTS: Males who had been born
      preterm exhibited lower morning cortisol and non-significantly elevated evening
      cortisol, resulting in a more adverse, flatter rate of decline across the day. In
      contrast, there were no significant differences by preterm status in cortisol
      measured at any time of day in females. CONCLUSIONS: These findings point to
      potential long-term effects of having been born preterm on adult HPA-axis
      function, and add to evidence from this and other populations for sex differences
      in the biological and health impacts of prenatal stress exposure.

PMID- 24898416
TI  - Arthroscopic treatment in split depression-type tibial pilon fracture.
AB  - Treatment of tibial pilon fractures is complicated and often very invasive.
      Partial fractures with a depressed component raise the question of the choice of
      surgical technique. Minimally invasive surgical reduction under arthroscopic
      guidance appears to be a promising alternative in this type of fracture. We
      describe a technique for arthroscopically assisted treatment of a split
      depression tibial pilon fracture. 

PMID- 24898417
TI  - Stable isotopes complement focal individual observations and confirm dietary
      variability in reddish-gray mouse lemurs (Microcebus griseorufus) from
      southwestern Madagascar.
AB  - We examine the ecology of reddish-gray mouse lemurs from three habitats at Beza
      Mahafaly Special Reserve using focal follows and stable carbon and nitrogen
      isotope data. Focal observations indicate dietary differences among habitats as
      well as sexes and seasons. Both sexes consume more arthropods during the rainy
      season but overall, females consume more sugar-rich exudates and fruit than
      males, and individuals from riparian forest consume fewer arthropods and more
      fruit than those in xeric or dry forest. We ask whether these observations are
      isotopically detectable. Isotope data support differences between seasons and
      sexes. Nitrogen isotope values are higher during the rainy season when lemurs
      consume more arthropods, and higher in males than females, particularly during
      the dry season. However, differences among populations inferred from focal
      observations are not fully supported. Lemurs from riparian forest have lower
      isotope values than those in xeric scrub, but isotope data suggest that lemurs
      from the dry forest eat the least animal matter and that focal observations
      overestimated dry forest arthropod consumption. Overall, our results suggest that
      observational and isotopic data are complementary. Isotope data can be obtained
      from a larger number of individuals and can quantify ingestion of animal matter,
      but they apparently cannot quantify the relative consumption of different sugar
      rich foods. Combined focal and isotope data provide valuable insight into the
      dietary constraints of reddish-grey mouse lemurs, with implications for their
      vulnerability to future habitat change.

PMID- 24898418
TI  - Comparison of clinical outcomes in nonintubated patients with severe alcohol
      withdrawal syndrome treated with continuous-infusion sedatives: dexmedetomidine
      versus benzodiazepines.
AB  - STUDY OBJECTIVE: To compare efficacy and safety outcomes in nonintubated patients
      with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion
      of a benzodiazepine or dexmedetomidine in addition to standard medical therapy
      for AWS. DESIGN: Retrospective cohort study. SETTING: Two hospitals within the
      same network that used different treatment strategies for AWS. PATIENTS: A total
      of 61 nonintubated adults who received a continuous infusion of either a
      benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine
      (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012,
      as well as standard medical therapy for AWS. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was a composite end point including rates of respiratory distress
      requiring endotracheal intubation or occurrence of alcohol withdrawal seizures.
      No significant differences in the composite end point were noted between the BZD
      and DEX groups (9.1% and 7.1%, respectively, p>0.99) or its individual components
      of respiratory distress (9.1% and 7.1%, respectively, p>0.99) or alcohol
      withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a
      lower median total dose of lorazepam equivalents after initiation of the study
      drug (median [interquartile range] 105 [60-199.5] mg in the BZD group vs 3.5 [0
      12] mg in the DEX group), but this did not translate into a reduced requirement
      for endotracheal intubation or decreased length of stay. DEX was associated with
      more adverse drug events including hypotension and bradycardia. Of concern, DEX
      may impair the ability to assess symptoms appropriately and administer BZDs in a
      symptom-triggered fashion. Although the total cost of hospitalization was similar
      between groups, DEX was associated with a higher study drug cost per patient.
      CONCLUSION: DEX demonstrated a BZD-sparing effect in the treatment of AWS;
      however, this surrogate end point should be interpreted with caution. Although
      this study cannot disprove the possibility of a protective effect of DEX in
      preventing the requirement for endotracheal intubation in patients with AWS, an
      increased rate of adverse drug events and increased study drug costs were
      observed. If DEX is used in clinical practice, it should only be used as
      adjunctive therapy with BZDs that have a proven benefit in AWS.

PMID- 24898419
TI  - Defined alpha-synuclein prion-like molecular assemblies spreading in cell
      culture.
AB  - BACKGROUND: alpha-Synuclein (alpha-syn) plays a central role in the pathogenesis
      of synucleinopathies, a group of neurodegenerative disorders that includes
      Parkinson disease, dementia with Lewy bodies and multiple system atrophy. Several
      findings from cell culture and mouse experiments suggest intercellular alpha-syn
      transfer. RESULTS: Through a methodology used to obtain synthetic mammalian
      prions, we tested whether recombinant human alpha-syn amyloids can promote prion
      like accumulation in neuronal cell lines in vitro. A single exposure to amyloid
      fibrils of human alpha-syn was sufficient to induce aggregation of endogenous
      alpha-syn in human neuroblastoma SH-SY5Y cells. Remarkably, endogenous wild-type
      alpha-syn was sufficient for the formation of these aggregates, and
      overexpression of the protein was not required. CONCLUSIONS: Our results provide
      compelling evidence that endogenous alpha-syn can accumulate in cell culture
      after a single exposure to exogenous alpha-syn short amyloid fibrils.
      Importantly, using alpha-syn short amyloid fibrils as seed, endogenous alpha-syn
      aggregates and accumulates over several passages in cell culture, providing an
      excellent tool for potential therapeutic screening of pathogenic alpha-syn
      aggregates.

PMID- 24898420
TI  - Performance and Maqasid al-Shari'ah's Pentagon-Shaped Ethical Measurement.
AB  - Business performance is traditionally viewed from the one-dimensional financial
      angle. This paper develops a new approach that links performance to the ethical
      vision of Islam based on maqasid al-shari'ah (i.e., the objectives of Islamic
      law). The approach involves a Pentagon-shaped performance scheme structure via
      five pillars, namely wealth, posterity, intellect, faith, and human self. Such a
      scheme ensures that any firm or organization can ethically contribute to the
      promotion of human welfare, prevent corruption, and enhance social and economic
      stability and not merely maximize its own performance in terms of its financial
      return. A quantitative measure of ethical performance is developed. It
      surprisingly shows that a firm or organization following only the financial
      aspect at the expense of the others performs poorly. This paper discusses further
      the practical instances of the quantitative measurement of the ethical aspects of
      the system taken at an aggregate level. 

PMID- 24898421
TI  - Lexical Retrieval of Nouns and Verbs in a Sentence Completion Task.
AB  - This study explored noun and verb retrieval using a sentence completion task to
      expand upon previous findings from picture naming tasks. Participants completed
      sentences missing either a target noun or verb in the final position. Non-target
      responses were coded for substitution type, imageability and frequency. Like
      picture naming, nouns and verbs differed in non-target substitution type-within
      category substitutions were primarily nouns and out-of-category substitutions
      were primarily verbs. Imageability predicted multiple substitution types for both
      word classes, whereas frequency predicted noun substitution types but not verbs.
      Findings support theories of noun and verb differences in semantic retrieval,
      showing the robustness of this effect across methodologies, and shed new light on
      the influence of imageability and frequency during semantic retrieval. 

PMID- 24898422
TI  - Rewiring mesenchymal stem cell lineage specification by switching the biophysical
      microenvironment.
AB  - The propensity of stem cells to specify and commit to a particular lineage
      program is guided by dynamic biophysical and biochemical signals that are
      temporally regulated. However, most in vitro studies rely on "snapshots" of cell
      state under static conditions. Here we asked whether changing the biophysical
      aspects of the substrate could modulate the degree of mesenchymal stem cell (MSC)
      lineage specification. We chose to explore two diverse differentiation outcomes:
      MSC osteogenesis and trans-differentiation to neuron-like cells. MSCs were
      cultured on soft (~0.5 kPa) or stiff (~40 kPa) hydrogels followed by transfer to
      gels of the opposite stiffness. MSCs on soft gels express elevated neurogenesis
      markers while MSCs on stiff substrates express elevated osteogenesis markers.
      Transfer of MSCs from soft to stiff or stiff to soft substrates led to a switch
      in lineage specification. However, MSCs transferred from stiff to soft substrates
      maintained elevated osteogenesis markers, suggesting a degree of irreversible
      activation. Transferring MSCs to micropatterned substrates reveal geometric cues
      that further modulate lineage reversal. Taken together, this study demonstrates
      that MSCs remain susceptible to the biophysical properties of the extracellular
      matrix--even after several weeks of culture--and can redirect lineage
      specification in response to changes in the microenvironment.

PMID- 24898423
TI  - Effect of diabetes mellitus on periprocedural myocardial infarction in patients
      undergoing coronary stent implantation.
AB  - BACKGROUND: Diabetic patients undergoing percutaneous coronary interventions are
      still regarded as a very high risk category because of an increased platelet
      reactivity and risk of complications, especially in patients with inadequate
      glycaemic control. However, although its prognostic effect on long-term outcome
      is well-defined, still unclear is the effect of diabetes on the risk of
      periprocedural myocardial infarction in patients undergoing percutaneous coronary
      interventions, which was therefore the aim of our study. METHODS: Myonecrosis
      biomarkers were dosed at intervals from 6 to 48 h after nonemergent percutaneous
      coronary interventions. Periprocedural myocardial infarction was defined as
      creatine kinase-MB increase by three times the upper limit normal or by 50% of an
      elevated baseline value, whereas periprocedural myonecrosis as troponin I
      increase by three times the upper limit normal or 50% of baseline. RESULTS: Of
      1311 patients, diabetes mellitus was found in 458 patients (34.9%) and associated
      with age (p = 0.03), hypertension (p < 0.001), renal failure (p = 0.01), previous
      MI (p = 0.03), previous coronary revascularization (p < 0.001), higher fasting
      glycaemia and lower haemoglobin (p < 0.001), more severe coronary disease (p <
      0.001), multivessel percutaneous coronary interventions (p = 0.03), coronary
      calcification (p = 0.003) and in-stent restenosis (p < 0.001) but lower presence
      of thrombus (p = 0.03). Diabetic patients were receiving significantly more
      frequent specific pharmacological treatment at admission. Diabetic status did not
      influence the risk of periprocedural myocardial infarction or periprocedural
      myonecrosis [adjusted OR(95%CI) = 0.90(0.64-1.27), p = 0.57 and adjusted
      OR(95%CI) = 0.92(0.70-1.21), p = 0.55]. Amongst diabetic patients, we did not
      observe any effect of chronic glycaemic control on periprocedural myocardial
      infarction. CONCLUSIONS: Diabetic status, independent of chronic glycaemic
      control, is not associated with increased risk of periprocedural myocardial
      infarction and myonecrosis in patients undergoing percutaneous coronary
      interventions.

PMID- 24898424
TI  - Prediction of the extent and variation of grapefruit juice-drug interactions from
      the pharmacokinetic profile in the absence of grapefruit juice.
AB  - The aim of this study was to develop a method for predicting the extent of
      grapefruit juice (GFJ)-drug interactions and their interindividual variations
      from the pharmacokinetic profile in the absence of GFJ. The pharmacokinetic
      profiles of 13 drugs after intravenous and oral administration were used to
      develop and validate the method. For each drug, the proportion absorbed into the
      intestine and the intestinal availability (Fg ) were calculated from clinical
      data taken from the literature. Then, the AUC ratio (the ratio of the AUC with
      GFJ to that without GFJ) was predicted by assuming that Fg was 1.0 when GFJ was
      concomitantly ingested. According to the developed method, the AUC ratio of
      felodipine was 2.50 and its coefficient of variation (CV) was 45%, which agreed
      well with the observed AUC ratio of 2.48 and CV of 51%. Although the developed
      method overestimated the AUC ratios of some drugs such as nisoldipine, no
      underestimation occurred. The predicted CV values were consistent with those
      observed. The developed method might be useful to predict the AUC ratio, along
      with its interindividual variation, from the pharmacokinetic profile in the
      absence of grapefruit juice.

PMID- 24898425
TI  - Chromosomal instability associated with global DNA hypomethylation is associated
      with the initiation and progression of esophageal squamous cell carcinoma.
AB  - BACKGROUND: Global DNA hypomethylation is associated with increased chromosomal
      instability and plays an important role in tumorigenesis. The methylation status
      of the long interspersed nuclear element-1 (LINE-1) element is a useful surrogate
      marker for global DNA methylation. Although LINE-1 hypomethylation is recognized
      as a poor prognostic marker, the correlation of LINE-1 methylation level with
      tumor suppressor gene mutation, chromosomal instability, and clinical
      significance in esophageal squamous cell carcinoma (ESCC) remains unclear.
      METHODS: Using resected tumor tissues and the corresponding normal esophageal
      mucosa from 105 patients with ESCC, bisulfite pyrosequencing analysis was
      performed to quantify the LINE-1 methylation levels. p53 mutations in exons two
      to ten were detected by polymerase chain reaction direct sequencing. Chromosomal
      instability was assessed by single nucleotide polymorphism array comparative
      genomic hybridization analysis. RESULTS: The LINE-1 methylation level of ESCC was
      significantly lower than matched normal mucosa. LINE-1 methylation levels of
      normal mucosa from the esophagus had a significant inverse correlation with both
      cigarette smoking and alcohol consumption of the study subjects. LINE-1
      hypomethylation of ESCC was significantly associated with lymph node metastasis,
      lymphovascular invasion, the frequency of p53 mutation and poor survivability.
      The LINE-1 methylation levels in ESCC had a significant inverse association with
      the percentage of copy number alterations in the whole genome, mirroring
      chromosomal instability. CONCLUSIONS: Our results suggested that whole genome
      hypomethylation caused by chronic inflammation could initiate carcinogenesis of
      esophageal squamous cells through chromosomal instability. In addition,
      chromosomal instability associated with the global hypomethylation might
      correlate highly with the progression of ESCC.

PMID- 24898426
TI  - Prediction of incident hip fracture with the estimated femoral strength by finite
      element analysis of DXA Scans in the study of osteoporotic fractures.
AB  - A bone fractures only when loaded beyond its strength. The purpose of this study
      was to determine the association of femoral strength, as estimated by finite
      element (FE) analysis of dual-energy X-ray absorptiometry (DXA) scans, with
      incident hip fracture in comparison to hip bone mineral density (BMD), Fracture
      Risk Assessment Tool (FRAX), and hip structure analysis (HSA) variables. This
      prospective case-cohort study included a random sample of 1941 women and 668
      incident hip fracture cases (295 in the random sample) during a mean +/- SD
      follow-up of 12.8 +/- 5.7 years from the Study of Osteoporotic Fractures (n =
      7860 community-dwelling women >=67 years of age). We analyzed the baseline DXA
      scans (Hologic 1000) of the hip using a validated plane-stress, linear-elastic
      finite element (FE) model of the proximal femur and estimated the femoral
      strength during a simulated sideways fall. Cox regression accounting for the case
      cohort design assessed the association of estimated femoral strength with hip
      fracture. The age-body mass index (BMI)-adjusted hazard ratio (HR) per SD
      decrease for estimated strength (2.21; 95% CI, 1.95-2.50) was greater than that
      for total hip (TH) BMD (1.86; 95% CI, 1.67-2.08; p < 0.05), FN BMD (2.04; 95% CI,
      1.79-2.32; p > 0.05), FRAX scores (range, 1.32-1.68; p < 0.0005), and many HSA
      variables (range, 1.13-2.43; p < 0.005), and the association was still
      significant (p < 0.05) after further adjustment for hip BMD or FRAX scores. The
      association of estimated strength with incident hip fracture was strong
      (Harrell's C index 0.770), significantly better than TH BMD (0.759; p < 0.05) and
      FRAX scores (0.711-0.743; p < 0.0001), but not FN BMD (0.762; p > 0.05). Similar
      findings were obtained for intracapsular and extracapsular fractures. In
      conclusion, the estimated femoral strength from FE analysis of DXA scans is an
      independent predictor and performs at least as well as FN BMD in predicting
      incident hip fracture in postmenopausal women.

PMID- 24898427
TI  - In vitro extraction of intra-corneal iron using reverse iontophoresis and vitamin
      C.
AB  - PURPOSE: The aim of this study was to optimize reverse iontophoretic (RI)
      extraction of ferric/ferrous ions from the cornea. METHODS: Group I consisted of
      the right eye corneas from 20 normal rabbits. Corneal blood staining was induced
      in 60 right eyes. The corneal depths from the endothelium to the epithelium
      layers were divided into three groups by slit-lamp examination: Group II, one
      third corneal thickness; Group III, one-half corneal thickness; Group IV, full
      corneal thickness. RI was performed using vertical diffusion cells. The lower
      chamber was loaded with glutathione bicarbonate Ringer's buffer (GBR; pH 7.0) or
      vitamin C (12.5 mg/mL) and GBR (pH 7.0), while the upper chamber was filled with
      1 mL GBR. Progress of corneal blood staining removal was evaluated. RESULTS:
      Application of 1.5 mA to the cornea increased flux by 1.72- and 2.19-fold in
      Groups III and IV, respectively, but not in Groups I or II, compared to the
      control. When vitamin C was included, we observed significant flux increases in
      the controls (1.5-, 2.06-, 2.60-, and 4.59-fold) for Groups I, II, III, and IV,
      and under RI conditions for Groups III and IV. Following RI, the corneal
      endothelia appeared similar to corneas from untreated control rabbits, while
      Draize scores were zero. CONCLUSIONS: These results suggested that extracellular
      ferric/ferrous ions could be extracted from the cornea in vitro by RI, and that
      vitamin C reduced Fe(3+) to Fe(2+) in the cornea and altered its permselectivity,
      thus increasing the RI contribution to iron extraction.

PMID- 24898429
TI  - The molecular basis of conjugated polyyne biosynthesis in phytopathogenic
      bacteria.
AB  - Polyynes (polyacetylenes), which are produced by a variety of organisms, play
      important roles in ecology. Whereas alkyne biosynthesis in plants, fungi, and
      insects has been studied, the biogenetic origin of highly unstable bacterial
      polyynes has remained a riddle. Transposon mutagenesis and genome sequencing
      unveiled the caryoynencin (cay) biosynthesis gene cluster in the plant pathogen
      B. caryophylli, and homologous gene clusters were found in various other bacteria
      by comparative genomics. Gene inactivation and phylogenetic analyses revealed
      that novel desaturase/acetylenase genes mediate bacterial polyyne assembly. A
      cytochrome P450 monooxygenase is involved in the formation of the allylic alcohol
      moiety, as evidenced by analysis of a fragile intermediate, which was stabilized
      by an in situ click reaction. This work not only grants first insight into
      bacterial polyyne biosynthesis but also demonstrates that the click reaction can
      be employed to trap fragile polyynes from crude mixtures. 

PMID- 24898428
TI  - Microaneurysm count as a predictor of long-term progression in diabetic
      retinopathy in young patients with type 1 diabetes: the Danish Cohort of
      Pediatric Diabetes 1987 (DCPD1987).
AB  - PURPOSE: To investigate microaneurysm (MA) count as a predictor of long-term
      progression of diabetic retinopathy (DR) in young patients with type 1 diabetes
      mellitus (T1DM). METHODS: We examined 185 patients with T1DM at baseline (1995)
      and at follow-up (2011). At baseline, mean age and duration of diabetes were 20.6
      and 12.9 years, respectively. Two-field (1995) and seven-field (2011) fundus
      photographs were taken in accordance with the European Diabetes Study Group
      (EURODIAB) and the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol,
      respectively. DR was graded in accordance to the ETDRS protocol, allowing for non
      standard photography at baseline. Baseline MAs were counted; patients without DR
      and those with MAs only were included. Multivariable logistic regressions were
      performed to investigate MA-count as a predictor of two-step progression,
      progression to proliferative DR (PDR), and incident diabetic macula edema (DME).
      RESULTS: We included 138 patients (138 eyes). Of these, 58 had no retinopathy and
      80 had MAs only. At follow-up, rates of two-step progression of DR, progression
      to PDR and incident DME were 52.9, 21.7, and 10.1 %, respectively. In logistic
      regression models, MA count was able to predict progression to PDR (OR: 1.51 per
      MA; 95 % CI: [1.04-2.20]) and DME (OR: 1.69 per MA; 95 % CI: [1.05-2.77]), but
      not two-step progression (OR 0.91 per MA, 95 % CI: [0.64-1.31]). CONCLUSIONS: In
      younger patients with T1DM, MA count predicts long-term incidence of PDR and DME.
      This demonstrates that early DR is a warning sign of late retinopathy
      complications and that the number of MAs is an important factor for long-term
      outcome.

PMID- 24898431
TI  - Developments in spiritual care education in German--speaking countries.
AB  - BACKGROUND: This article examines spiritual care training provided to healthcare
      professionals in Germany, Austria and Switzerland. The paper reveals the current
      extent of available training while defining the target group(s) and teaching
      aims. In addition to those, we will provide an analysis of delivered
      competencies, applied teaching and performance assessment methods. METHODS: In
      2013, an anonymous online survey was conducted among the members of the
      International Society for Health and Spiritual Care. The survey consisted of 10
      questions and an open field for best practice advice. SPSS21 was used for
      statistical data analysis and the MAXQDA2007 for thematic content analysis.
      RESULTS: 33 participants participated in the survey. The main providers of
      spiritual care training are hospitals (36%, n = 18). 57% (n = 17) of spiritual
      care training forms part of palliative care education. 43% (n = 13) of spiritual
      care education is primarily bound to the Christian tradition. 36% (n = 11) of
      provided trainings have no direct association with any religious conviction. 64%
      (n = 19) of respondents admitted that they do not use any specific definition for
      spiritual care. 22% (n = 14) of available spiritual care education leads to some
      academic degree. 30% (n = 19) of training form part of an education programme
      leading to a formal qualification. Content analysis revealed that spiritual
      training for medical students, physicians in paediatrics, and chaplains take
      place only in the context of palliative care education. Courses provided for
      multidisciplinary team education may be part of palliative care training. Other
      themes, such as deep listening, compassionate presence, bedside spirituality or
      biographical work on the basis of logo-therapy, are discussed within the
      framework of spiritual care. CONCLUSIONS: Spiritual care is often approached as
      an integral part of grief management, communication/interaction training,
      palliative care, (medical) ethics, psychological or religious counselling or
      cultural competencies. Respondents point out the importance of competency based
      spiritual care education, practical training and maintaining the link between
      spiritual care education and clinical practice. Further elaboration on the
      specifics of spiritual care core competencies, teaching and performance
      assessment methods is needed.

PMID- 24898432
TI  - 'The land is now not fertile': social landscapes of hunger in south-eastern
      coastal Tanzania.
AB  - Based on ethnographic fieldwork in a coastal village in south-eastern Tanzania,
      this paper examines how social inequalities and social suffering become embodied
      in the lived experiences of hunger. The paper explores local meanings of food,
      fertility and hunger and how these concepts interconnect and materialize on a
      landscape impacted by two large-scale conservation and development projects, the
      Mtwara Development Corridor and the Mnazi Bay Ruvuma Estuary Marine Park.
      Fourteen in-depth interviews Sinde villagers were conducted to elicit narratives
      about their food experiences in addition to 24 hour food recall and pile sort to
      explore local taxonomies of food. One focus group discussion with six women was
      also conducted. The study finds displacement from resources by the conservation
      and development projects has exacerbated existing food security issues of
      irregular rains, increasing food prices and malnourished bodies. The downward
      cycle of food insecurity has local villagers worried about the viability of their
      community's future, embodied in the health of local children and their
      performance in school. Increasing food insecurity is internalized within the
      community as infertility where the health of the landscape is connected to the
      health of society.

PMID- 24898430
TI  - Induction of protective immune response against both PPRV and FMDV by a novel
      recombinant PPRV expressing FMDV VP1.
AB  - Peste des petits ruminants (PPR) and foot-and-mouth disease (FMD) are both highly
      contagious diseases of small domestic and wild ruminants caused by the PPR virus
      (PPRV) and the FMD virus (FMDV). In this study, a recombinant PPRV expressing the
      FMDV VP1 gene (rPPRV/VP1) was generated and FMDV VP1 expression did not impair
      replication of the recombinant virus in vitro and immunogenicity in inducing
      neutralizing antibody against PPR in goats. Vaccination with one dose of
      rPPRV/VP1 induced FMDV neutralizing antibody in goats and protected them from
      challenge with virulent FMDV. Our results suggest that the recombinant PPRV
      expressing the FMDV VP1 protein is a potential dual live vectored vaccine against
      PPRV and FMDV.

PMID- 24898433
TI  - [Anesthesia for upper limb surgery in a developing country: experience of
      infraclavicular and axillary blocks under neurostimulation].
AB  - ABSTRACT: Despite advances in regional anesthesia under ultrasound guidance,
      neurostimulation remains the primary technique in underequipped locations.
      MATERIAL AND METHODS: We conducted a prospective descriptive study from January
      to December 2010 and June 2011 to May 2012 with as our main objective the
      assessment of the practices of infraclavicular and axillary nerve blocks (ICB and
      AXB, respectively) at Sylvanus Olympio University Hospital. RESULTS: 105 patients
      (11.8%) received ICB) and 75 patients (8.5%) axillary blocks (AXB). The average
      minimum intensity of neurostimulation was 0.4 mA (range: 0.25-0.45 mA. The mean
      volume of 0.5% bupivacaine used was 30 +/- 10 mL. The mean onset time of the
      block was 15 +/- 10 min, and the mean duration of action 6 +/- 4 hours.
      Postoperative pain was significantly worse in patients who received ICB compared
      to AXB [chi(2) = 19.034, p = 0.00001<0.05]. The cost of either type of
      locoregional anesthesia under neurostimulation compared with general anesthesia
      was 44 euros versus 105 euros. CONCLUSION: Peripheral nerve block by ICB and AXB
      under neurostimulation showed significant difference in terms of postoperative
      analgesia efficiency. Locoregional anesthesia remains too rarely practiced in
      underequipped countries despite its benefits and although it is particularly
      appropriate for these countries.

PMID- 24898434
TI  - Diagnosis of hyperfunctional thyroid nodules: impact of US-elastography.
AB  - AIM: Several studies described the ultrasound based real-time elastography (USE)
      having a high sensitivity, specificity and negative predictive value in the
      diagnosis of suspicious thyroid nodules. Recently published studies called these
      results into question. Until now the usefulness of USE in the diagnosis of
      scintigraphically hyperfunctional thyroid nodules is not examined. PATIENTS,
      METHODS: This study included 135 hyperfunctional thyroid nodules of 102
      consecutive patients. The following attributes of the nodules were analyzed:
      stiffness with the USE using scores of Rago or Asteria and ultrasound criteria
      using TIRADS. RESULTS: 94 of the examined thyroid nodules (70%) were rated as
      hard (suspicious for malignancy) and 41 nodules (30%) as soft (not suspicious)
      with a specificity of 30%. The scoring systems of Rago and Asteria showed no
      significant difference. Applying the TIRADS criteria 44 nodules (33%) have a
      higher risk for malignancy (33 nodules TIRADS 4a, 11 nodules TIRADS 4b).
      Combining USE and TIRADS 32 nodules (24%) are categorized as suspicious
      (intersection of hard nodules that are categorized as TIRADS 4a or 4b).
      CONCLUSION: Ultrasound based real-time elastography cannot identify
      scintigraphically hyperfunctional thyroid nodules as benign nodules reliably. Its
      accuracy in the assessment of at least "hot" thyroid nodules is to be questioned.

PMID- 24898435
TI  - Development and characterization of elastic nanocomposites for craniofacial
      contraction osteogenesis.
AB  - Development of resorbable elastic composites as an alternative means to apply
      contractive forces for manipulating craniofacial bones is described herein.
      Composites made from the biodegradable elastomer, poly (1,8-octanediol co-citric
      acid) (POC), and hydroxyapatite (nHA) with a 200 nm diameter (0-20% loadings)
      were created to develop a material capable of applying continuous contractive
      forces. The composites were evaluated for variation in their mechanical
      properties, rate of degradation, and interaction of the hydroxyapatite
      nanoparticles with the polymer chains. First, an ex vivo porcine model of cleft
      palate was used to determine the rate of cleft closure with applied force. The
      closure rate was found to be 0.505 mm N(-1) . From this approximation, the ideal
      maximum load was calculated to be 19.82 N, and the elastic modulus calculated to
      be 1.98 MPa. The addition of nHA strengthens POC, but also reduces the
      degradation time by 45%, for 3% nHA loading, compared to POC without nHA. X-ray
      diffraction data indicates that the addition of nHA to amorphous POC results in
      the formation of a semicrystalline phase of the POC adjacent to the nHA crystals.
      Based on the data, we conclude that amongst the 0-20% nHA loadings, a 3% loading
      of nHA in POC may be an ideal material (1.21 MPa elastic modulus and 13.17 N
      maximum load) to induce contraction forces capable of facilitating osteogenesis
      and craniofacial bone repair.

PMID- 24898436
TI  - The influence of women's preferences and actual mode of delivery on post
      traumatic stress symptoms following childbirth: a population-based, longitudinal
      study.
AB  - BACKGROUND: This study aimed to examine whether a mismatch between a woman's
      preferred and actual mode of delivery increases the risk of post-traumatic stress
      symptoms after childbirth. METHODS: The study sample consisted of 1,700 women
      scheduled to give birth between 2009 and 2010 at Akershus University Hospital,
      Norway. Questionnaire data from pregnancy weeks 17 and 32 and from 8 weeks
      postpartum were used along with data obtained from hospital birth records. Post
      traumatic stress symptoms were measured with the Impact of Event Scale. Based on
      the women's preferred and actual mode of delivery, four groups were established:
      Match 1 (no preference for cesarean section, no elective cesarean section, N =
      1,493); Match 2 (preference for cesarean section, elective cesarean section, N =
      53); Mismatch 1 (no preference for cesarean section, elective cesarean section, N
      = 42); and Mismatch 2 (preference for cesarean section, no elective cesarean
      section, N = 112). Analysis of variance (ANOVA) and analysis of covariance
      (ANCOVA) were conducted to examine whether the level of post-traumatic stress
      symptoms differed significantly among these four groups. RESULTS: Examining
      differences for all four groups, ANOVA yielded significant overall group
      differences (F = 11.96, p < 0.001). However, Bonferroni post-hoc tests found
      significantly higher levels of post-traumatic stress symptoms only in Mismatch 2
      compared to Match 1. This difference could be partly explained by a number of
      risk factors, particularly psychological risk factors such as fear of childbirth,
      depression, and anxiety. CONCLUSIONS: The results suggest increased post
      traumatic stress symptoms in women who preferred delivery by cesarean section but
      delivered vaginally compared to women who both preferred vaginal delivery and
      delivered vaginally. In psychologically vulnerable women, such mismatch may
      threaten their physical integrity and, in turn, result in post-traumatic stress
      symptoms. These women, who often fear childbirth, may prefer a cesarean section
      even though vaginal delivery is usually the best option in the absence of medical
      indications. To avoid potential trauma, fear of childbirth and maternal requests
      for a cesarean section should be taken seriously and responded to adequately.

PMID- 24898437
TI  - Emergency contraception.
AB  - This review summarises the development of emergency contraception (EC) methods,
      and provides an overview on the currently available options of EC which are
      effective and safe back-up methods in case of non-use or failure of the regular
      contraception. The copper intrauterine contraceptive device is currently the most
      effective method. In most countries, a single dose of levonorgestrel 1.5 mg is
      the first-line hormonal EC given within 72 h of unprotected intercourse. The oral
      anti-progestogens such as mifepristone and ulipristal acetate are promising
      alternatives with better efficacies and a wider treatment window of up to 120 h
      post coitus, probably resulting from more diverse ancillary mechanisms of
      actions. Education on EC should be part of any contraceptive counselling.
      Improving access to EC by providing it over the counter or in advance would not
      promote its abuse nor encourage risky sexual behaviours, but may further
      facilitate the timely use so as to achieve the best efficacy.

PMID- 24898438
TI  - Trunk muscle activity with different sitting postures and pelvic inclination.
AB  - BACKGROUND AND OBJECTIVE: Sitting posture may often place large burden on trunk
      muscles, while trunk muscle activities in the sitting posture have not been well
      clarified. In this study, a difference in trunk muscle activity between two kinds
      of sitting postures was evaluated, focusing on low back pain induced by posture
      holding. MATERIAL AND METHODS: An experiment was conducted on the subjects
      sitting on a stable-seat and on an unstable-seat, with the pelvis inclined
      forward, backward, rightward, and leftward. RESULTS: With the pelvis inclined
      forward, rightward and leftward, muscle activities were significantly increased
      in a stable-seat sitting posture. In contrast, no significant increase in muscle
      activity was observed with the pelvis inclined in every direction in an unstable
      seat sitting posture. CONCLUSIONS: With the pelvis inclined in the stable-seat
      sitting posture, muscle activities were imbalanced, while with the pelvis
      inclined in the unstable-seat sitting posture, muscle activities were not
      imbalanced. Thus, it is suggested that with the pelvis inclined to the maximum
      extent in the stable-seat sitting posture, low back pain may be induced by
      imbalanced muscle activities.

PMID- 24898439
TI  - Autosomal Dominant Osteopetrosis Type II.
AB  - Osteopetrosis is a rare genetic disorder caused by osteoclast failure. Dominant
      negative mutations of the ClCN7 gene cause the so-called, autosomal dominant
      osteopetrosis type II, which represents the most frequent and heterogeneous form
      of osteopetrosis, ranging from asymptomatic to intermediate-severe, thus
      suggesting additional genetic and environmental determinants affecting
      penetrance. Here, we present a case a 46 year-old woman complained low back pain
      for 15 years. The patient lacked any history of direct trauma and her pain was
      radiating to her left leg, increasing with physical activity, she had no pain at
      nights. The patient was diagnosed with autosomal dominant osteopetrosis on the
      basis of the presence of typical radiological appearance. Were present a case
      report of osteopetrosis type II (an autosomal dominantly inherited disease) as a
      cause for low back pain without any familial penetrance of the disease.

PMID- 24898440
TI  - Scheuermann's disease: current diagnosis and treatment approach.
AB  - OBJECTIVES: To summarize the current knowledge relating to diagnosing and
      treating Scheuermann's disease. Scheuermann's disease is the most common cause of
      structural kyphosis in adolescence. METHODS: A literature-based narrative review
      of English language medical literature. RESULTS AND CONCLUSIONS: Recent studies
      have revealed a major genetic contribution (a dominant autosomal inheritance
      pattern with high penetrance and variable expressivity) to the etiology of
      Scheuermann kyphosis with a smaller environmental component (most probably
      mechanical factors). The natural history of Scheuermann kyphosis remains
      controversial, with conflicting reports as to the severity of pain and physical
      disability. Since we cannot predict which kyphotic curves will progress, we are
      unable to determine effectiveness of brace treatment. Physical therapy is
      scarcely mentioned in the literature as an effective treatment for Scheuermann
      kyphosis. Although there is little evidence that physical therapy alone can alter
      the natural history of Scheuermann's disease, it is often used as the first
      choice of treatment. Brace treatment appears to be more effective if an early
      diagnosis is made, prior to the curvature angle exceeding 50 degrees  in patients
      continuing to grow. Surgical treatment is rarely indicated for severe kyphosis
      (>75 degrees ) with curve progression, refractory pain, or a neurologic deficit.
      Rigorous methodology clinical trials are essential to evaluate the efficacy of
      conservative interventions, especially different exercises and manual therapies
      and their combinations with braces.

PMID- 24898441
TI  - Enhanced extraordinary optical transmission (EOT) through arrays of bridged
      nanohole pairs and their sensing applications.
AB  - Extraordinary optical transmission (EOT) through arrays of gold nanoholes was
      studied with light across the visible to the near-infrared spectrum. The EOT
      effect was found to be improved by bridging pairs of nanoholes due to the
      concentration of the electromagnetic field in the slit between the holes. The
      geometrical shape and separation of the holes in these pairs of nanoholes
      affected the intensity of the transmission and the wavelength of resonance.
      Changing the geometrical shapes of these nanohole pairs from triangles to circles
      to squares leads to increased transmission intensity as well as red-shifting
      resonance wavelengths. The performance of bridged nanohole pairs as a plasmonic
      sensor was investigated. The bridged nanohole pairs were able to distinguish
      methanol, olive oil and microscope immersion oil for the different surface
      plasmon resonance in transmission spectra. Numerical simulation results were in
      agreement with experimental observations. 

PMID- 24898442
TI  - Scrotal bullous pemphigoid in an elderly patient.

PMID- 24898444
TI  - The influence of nominal stress on wear factors of carbon fibre-reinforced
      polyetheretherketone (PEEK-OPTIMA(r) Wear Performance) against zirconia toughened
      alumina (Biolox(r) delta ceramic).
AB  - Carbon fibre-reinforced polyetheretherketone is an attractive alternative to
      ultra-high-molecular-weight polyethylene in artificial joints, but little has
      been published on the influence of stress on the wear factor. We know that in
      ultra-high-molecular-weight polyethylene, the wear factor reduces as the normal
      stress increases, which is counter-intuitive but very helpful in the case of non
      conforming contacts. In this study, carbon fibre-reinforced polyetheretherketone
      (PEEK-OPTIMA(r) Wear Performance) has been investigated in a pin-on-plate machine
      under steady loads and under stresses typical of hip and knee joints. At stresses
      below about 6 MPa, wear factors are between 10 and a 100 times lower than for
      ultra-high-molecular-weight polyethylene but at higher stresses the wear factors
      increase substantially.

PMID- 24898443
TI  - Biphasic investigation of contact mechanics in natural human hips during
      activities.
AB  - The aim of this study was to determine the cartilage contact mechanics and the
      associated fluid pressurisation of the hip joint under eight daily activities,
      using a three-dimensional finite element hip model with biphasic cartilage layers
      and generic geometries. Loads with spatial and temporal variations were applied
      over time and the time-dependent performance of the hip cartilage during walking
      was also evaluated. It was found that the fluid support ratio was over 90% during
      the majority of the cycles for all the eight activities. A reduced fluid support
      ratio was observed for the time at which the contact region slid towards the
      interior edge of the acetabular cartilage, but these occurred when the absolute
      level of the peak contact stress was minimal. Over 10 cycles of gait, the peak
      contact stress and peak fluid pressure remained constant, but a faster process of
      fluid exudation was observed for the interior edge region of the acetabular
      cartilage. The results demonstrate the excellent function of the hip cartilage
      within which the solid matrix is prevented from high levels of stress during
      activities owing to the load shared by fluid pressurisation. The findings are
      important in gaining a better understanding of the hip function during daily
      activities, as well as the pathology of hip degeneration and potential for future
      interventions. They provide a basis for future subject-specific biphasic
      investigations of hip performance during activities.

PMID- 24898445
TI  - Design and testing of a cyclic stretch and flexure bioreactor for evaluating
      engineered heart valve tissues based on poly(glycerol sebacate) scaffolds.
AB  - Cyclic flexure and stretch are essential to the function of semilunar heart
      valves and have demonstrated utility in mechanically conditioning tissue
      engineered heart valves. In this study, a cyclic stretch and flexure bioreactor
      was designed and tested in the context of the bioresorbable elastomer
      poly(glycerol sebacate). Solid poly(glycerol sebacate) membranes were subjected
      to cyclic stretch, and micromolded poly(glycerol sebacate) scaffolds seeded with
      porcine aortic valvular interstitial cells were subjected to cyclic stretch and
      flexure. The results demonstrated significant effects of cyclic stretch on
      poly(glycerol sebacate) mechanical properties, including significant decreases in
      effective stiffness versus controls. In valvular interstitial cell-seeded
      scaffolds, cyclic stretch elicited significant increases in DNA and collagen
      content that paralleled maintenance of effective stiffness. This work provides a
      basis for investigating the roles of mechanical loading in the formation of
      tissue-engineered heart valves based on elastomeric scaffolds.

PMID- 24898446
TI  - MDR1 C3435T polymorphism associated with the development of clinical features in
      Behcet's disease in Iranian Azeri Turkish patients.
AB  - BACKGROUND: Behcet's disease (BD) is a systemic vasculitis of unknown cause with
      a higher prevalence along the ancient Silk Road. Behcet's occasional familial
      aggregation and its close association with genes of major histocompatibility
      complexes justify that genetic factors play an important role in the development
      of the disease. In this study, we evaluated the association of multidrug
      resistance (MDR1) C3435T polymorphism with the severity of BD. METHOD: We
      investigated the distribution of MDR1 C3435T polymorphism in 69 patients from the
      Iranian Azeri Turks group with BD and 92 ethnically sex-matched healthy controls,
      via the polymerase chain reaction-restriction fragment length polymorphism
      technique. RESULT: Although there was no significant association of MDR1 C3435T
      polymorphism between two groups of patients and healthy controls, our data showed
      a substantial association of CC genotype with the development of several clinical
      features, including erythema nodosum (P = 0.001, OR = 2.686, 95%),
      pseudofolliculitis (P = 0.002, OR = 2.812, 95%), and skin lesions (P = 0.040, OR
      = 1.934, 95%). CONCLUSION: These results suggest that CC genotype is a risk
      factor for the development of some clinical features of BD in patients from the
      Iranian Azeri Turk ethnic group.

PMID- 24898448
TI  - Synthesis and spectroscopic properties of chiral binaphthyl-linked
      subphthalocyanines.
AB  - Chiral binaphthyl-linked subphthalocyanines (SubPcs) (1) have been prepared by
      the cyclotrimerization reaction of a phthalonitrile linked with (R)- and (S)-2,2'
      binaphthyl in the presence of BCl3, and characterized by various spectroscopies
      including NMR, electronic absorption, CD, and MCD, as well as electrochemistry.

PMID- 24898449
TI  - Defining a pro-inflammatory neutrophil phenotype in response to schistosome eggs.
AB  - Neutrophils contribute to the pathological processes of a number of inflammatory
      disorders, including rheumatoid arthritis, sepsis and cystic fibrosis.
      Neutrophils also play prominent roles in schistosomiasis japonica liver fibrosis,
      being central mediators of inflammation following granuloma formation. In this
      study, we investigated the interaction between Schistosoma japonicum eggs and
      neutrophils, and the effect of eggs on the inflammatory phenotype of neutrophils.
      Our results showed significant upregulated expression of pro-inflammatory
      cytokines (IL-1alpha, IL-1beta and IL-8) and chemokines (CCL3, CCL4 and CXCL2) in
      neutrophils after 4 h in vitro stimulation with S. japonicum eggs. Furthermore,
      mitochondrial DNA was released by stimulated neutrophils, and induced the
      production of matrix metalloproteinase 9 (MMP-9), a protease involved in
      inflammation and associated tissue destruction. We also found that intact live
      eggs and isolated soluble egg antigen (SEA) triggered the release of neutrophil
      extracellular traps (NETs), but, unlike those reported in bacterial or fungal
      infection, NETs did not kill schistosome eggs in vitro. Together these show that
      S. japonicum eggs can induce the inflammatory phenotype of neutrophils, and
      further our understanding of the host-parasite interplay that takes place within
      the in vivo microenvironment of schistosome-induced granuloma. These findings
      represent novel findings in a metazoan parasite, and confirm characteristics of
      NETs that have until now, only been observed in response to protozoan pathogens. 

PMID- 24898450
TI  - Micrometer-size vesicle formation triggered by UV light.
AB  - Vesicle formation is a fundamental kinetic process related to the vesicle budding
      and endocytosis in a cell. In the vesicle formation by artificial means,
      transformation of lamellar lipid aggregates into spherical architectures is a key
      process and known to be prompted by e.g. heat, infrared irradiation, and
      alternating electric field induction. Here we report UV-light-driven formation of
      vesicles from particles consisting of crumpled phospholipid multilayer membranes
      involving a photoactive amphiphilic compound composed of 1,4-bis(4
      phenylethynyl)benzene (BPEB) units. The particles can readily be prepared from a
      mixture of these components, which is casted on the glass surface followed by
      addition of water under ultrasonic radiation. Interestingly, upon irradiation
      with UV light, micrometer-size vesicles were generated from the particles.
      Neither infrared light irradiation nor heating prompted the vesicle formation.
      Taking advantage of the benefits of light, we successfully demonstrated
      micrometer-scale spatiotemporal control of single vesicle formation. It is also
      revealed that the BPEB units in the amphiphile are essential for this phenomenon.

PMID- 24898451
TI  - Evaluation of a new staging classification and a Peritoneal Surface Disease
      Severity Score (PSDSS) in 229 patients with mucinous appendiceal neoplasms with
      or without peritoneal dissemination.
AB  - INTRODUCTION: Most classifications of mucinous appendiceal neoplasms (MAN) do not
      take into consideration the type of primary tumor or the burden of peritoneal
      disease. MATERIALS AND METHODS: We conducted a retrospective evaluation of 229
      patients with MAN. The severity of their disease was analyzed with the Peritoneal
      Surface Disease Severity Score (PSDSS) on a five-point scale that included: (1)
      the primary appendiceal tumor, (2) the type of peritoneal dissemination, and (3)
      the burden of disease. Overall survival was analyzed according to five tiers of
      estimated disease severity based on the above parameters. RESULTS: There were 19,
      67, 59, 43, and 41 patients with PSDSS 0, I, II, III, and IV, respectively. One
      hundred seventy-three patients underwent cytoreductive surgery (CRS) and
      hyperthermic intraperitoneal chemotherapy (HIPEC). Overall survival was 80.0
      months in this group with 5-year survival of 100%, 79.2%, 23.3%, and 6.9% in
      patients with PSDSS I, II, III, and IV, respectively (P < 0.001). On multivariate
      analysis, sex and PSDSS stage were identified as independent predictors of
      survival. CONCLUSIONS: The PSDSS appears to be an important prognostic indicator
      in patients with MANs with or without peritoneal dissemination and may improve
      selection of patients for appropriate therapy from the time of diagnosis.

PMID- 24898452
TI  - Total nucleated cells as a sole predictor of distinct targets of hematopoietic
      potential (CD34+ cells) in cord blood units: the results of a large series
      analysis in autologous cord blood units.
AB  - BACKGROUND: Rapid identification of eligible cord blood units (CBUs) for banking
      is an important issue in hematopoietic stem cell procurement. Distinct contents
      of CD34+ cells in CBU can contribute to identify grafts that may be banked also
      for unrelated transplants or limited to family-directed or autologous use. STUDY
      DESIGN AND METHODS: Considering thresholds of CD34+ cell content of 3 * 10(6) , 2
      * 10(6) , and 1 * 10(6) CD34+ cells, we analyzed a consecutive series of 1309
      CBUs. CBUs were collected for autologous banking without any volume-based
      preselection criteria. Predictors of distinct content of CD34+ cells have been
      assessed by receiver operating characteristic (ROC) curve analysis. RESULTS:
      Median total nucleated cell (TNC) and CD34+ cell counts of the series were 6.97 *
      10(8) (range, 0.36 * 10(8) -34.9 * 10(8) ) and 1.47 * 10(6) (0-20.56 * 10(6) ).
      Volumes ranged from 21 to 163 mL, with a median of 73.8 mL. For the CD34+ target
      of 1 * 10(6) , the best predictor was TNC count with a threshold of 6.63 * 10(8)
      ; volume results were less predictive with a value of 68.1 mL. For CD34+ targets
      of 2 * 10(6) and 3 * 10(6) , ROC curves confirmed a stronger predictive power of
      TNC, above the collected volume, with thresholds of 7.55 * 10(8) and 8.98 * 10(8)
      . ROC analysis by combining all predictors (TNC, volume, TNC(2) , volume(2) , age
      of mothers, types of delivery, birthweight) gave worse results than TNC count
      alone. CONCLUSIONS: This analysis, carried out on a large, unrestricted CBU
      series, shows that TNC alone is the best predictor of distinct targets of
      hematopoietic potential with the chance to predict CBU potentially useful for
      unrelated recipients or limited for family-directed or autologous use.

PMID- 24898453
TI  - Allogeneic peripheral blood stem cell transplantation using reduced-intensity
      conditioning in an outpatient setting in ABO-incompatible patients: are survival
      and graft-versus-host disease different?
AB  - BACKGROUND: Graft-versus-host disease (GVHD) is a major cause of morbimortality
      after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Minor ABO
      incompatibility has been associated with an increased risk of GVHD. We analyzed
      the impact of ABO matching on patient outcome after peripheral blood, reduced
      intensity allo-HSCT in an outpatient setting, and its relationship with GVHD.
      STUDY DESIGN AND METHODS: Data of 121 patients were included. All patients
      received allo-HSCT from HLA-identical siblings as outpatients using a reduced
      intensity conditioning regimen. Influence of ABO matching as a risk factor for
      the development of GVHD and survival was analyzed using logistic regression and
      Cox proportional hazards regression, respectively. RESULTS: Median age was 36
      years (range, 1-71 years); 88 patients were ABO identical: 13 presented major
      mismatch and 20 minor mismatch, with an ABO incompatibility rate of 27.3%. The
      median follow-up period was 54 months (range, 0.3-120 months). Minor ABO
      incompatibility patients presented the highest rate of acute GVHD (aGVHD; 25%),
      in comparison with ABO-identical (20.5%) and major ABO incompatibility patients
      (15.4%; p = 0.79). The highest incidence of chronic GVHD (cGVHD) occurred in the
      context of minor ABO incompatibility (35%), in contrast to ABO-identical (30.8%)
      and major ABO incompatibility (15.4%). Survival was higher for patients in the
      minor ABO mismatch group; however, there was no significant correlation between
      ABO matching status and survival (p = 0.45). CONCLUSION: Using this type of
      peripheral blood stem cell transplantation, minor ABO-mismatched allo-HSCT was
      associated with a higher incidence of aGVHD and cGVHD and with increased
      survival, albeit with no significance.

PMID- 24898454
TI  - Defining a reference range for cold agglutinin titers.
AB  - BACKGROUND: The cold agglutinin (CAGG) titer is offered at our institution to aid
      in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally
      adjusted reference range using prospective samples and compare it to a reference
      range generated retrospectively. STUDY DESIGN AND METHODS: Prospective CAGG titer
      testing was performed on healthy blood donors. Retrospective electronic analysis
      was performed on patients in two groups defined by current and historical testing
      methods. Blood donor testing was performed in January and July to determine if
      seasonal variation existed. Retrospective patients with conditions associated
      with CAD were excluded from analysis. Additional prospective CAGG testing using
      reference range program volunteers was performed to verify blood donor and
      patient result differences. RESULTS: Titers from the blood donor and patient
      cohorts had no age association (p > 0.44). Titers from those same cohorts did not
      show winter/summer variation (p > 0.11). No sex association was found with titer
      reference ranges in the blood donor and historical patient cohort. A sex
      association was found with titers in the current method patient cohort (male 64
      to 512 and female <=64; p < 0.0001). Blood donor CAGG titer lower 95% reference
      range was not more than 4 while historical and current patient cohorts ranges
      were not more than 32 and not more than 64, respectively. Reference range
      volunteers confirmed the narrow reference range in healthy individuals when
      compared to patients and blood donors. CONCLUSION: Prospective blood donor CAGG
      titers were lower than retrospective patient cohorts. This may be due to blood
      donors representing a healthier population than the patient cohorts.

PMID- 24898455
TI  - The p.R168Q mutation is associated with the Bw phenotype and a predicted decrease
      in the stability of the resulting ABO glycosyltransferase.
AB  - BACKGROUND: Mutation of ABO glycosyltransferase (GT) can cause protein stability
      changes that can result in a weak ABO phenotype. To explain the Bw phenotype of a
      novel ABO*Bw allele, a protein stability of the mutant GT, which enhances the
      information of the three-dimensional (3D) structural analysis, was calculated.
      STUDY DESIGN AND METHODS: ABO serology and genotyping were performed on a neonate
      and her five family members. A 3D structural analysis of the wild-type GTB and
      enzymes with a variety of mutations at Residue 168, along with predicted protein
      stability changes (DeltaDeltaG) and flow cytometric analysis of ABO antigen
      expression on HeLa cells transfected with plasmids containing R168Q, R168L, and
      R168P mutants was also performed. RESULTS: A novel ABO*Bw allele (c.503G>A,
      p.R168Q) was discovered. The structural analysis of 3D homology modeling
      predicted reduced protein stability of the mutant GTB, and the DeltaDeltaG
      values, which inversely correlated with the mean relative fluorescence intensity
      of ABO antigen expression, quantitatively explained the reduced ABO antigen
      expression. CONCLUSIONS: The predicted protein stability change of a mutant GT
      enzyme might be a useful and convenient approach to objectively and
      quantitatively explain the reduced ABO antigen expression.

PMID- 24898456
TI  - Reduced use of allogeneic platelets through high-yield perioperative autologous
      plateletpheresis and reinfusion.
AB  - BACKGROUND: Intraoperative autologous platelet (PLT) collection as part of a
      multimodal blood conservation program carries a Class IIa recommendation from the
      Societies of Thoracic Surgeons and Cardiovascular Anesthesiologists, but
      achieving a suitable PLT yield limits its application. A novel, autologous,
      intraoperative, high-yield plateletpheresis collection program was established
      and retrospectively analyzed to identify potential improvements over previously
      reported plateletpheresis protocols. STUDY DESIGN AND M-ETHODS: Targeting complex
      cardiothoracic surgery patients without recent anti-PLT agents, thrombocytopenia,
      or severe anemia, the program aimed to achieve a PLT yield of at least one
      standard apheresis unit (3.0 * 10(11) ) within 60 to 90 minutes and using an
      automated plateletpheresis device (Trima, Terumo BCT). Anesthetized and
      invasively monitored patients underwent plateletpheresis via a large-bore,
      indwelling central line placed for the surgery. Collection-related data for
      quality control purposes and subsequent PLT transfusion requirements were
      analyzed and reported. RESULTS: Forty-two patients donated autologous PLTs
      between 2011 and 2012. PLT yield was 4.5 (3.9-5.0) * 10(11) , which significantly
      exceeds previously reported yields, and procedure duration was 53.2 (48.4-57.9)
      minutes. As anticipated, postcollection PLT count decreased from 268 (242-293) *
      10(9) to 182 (163-201) * 10(9) /L; hypocalcemia was minimized by infusion of 1 g
      of CaCl2 . Autologous PLT yield was inversely correlated with allogeneic PLT use,
      and avoidance of allogeneic PLT transfusion was increased when the autologous
      yield was the equivalent of 2 or more apheresis units. CONCLUSION: High-yield,
      intraoperative autologous PLT collection is achievable using an automated
      plateletpheresis device. Initial experience shows a reduction in reliance on
      allogeneic PLTs for complex cardiothoracic surgery.

PMID- 24898457
TI  - Neonatal blood transfusion as transmission route in chronic hepatitis C.
AB  - BACKGROUND: The aim of this study was to investigate if neonatal transfusions
      could underlie chronic hepatitis C in adults for whom the disease transmission
      route was previously unknown. STUDY DESIGN AND METHODS: Questionnaires were sent
      to 255 patients with chronic hepatitis C born in Sweden in 1960 to 1975. The
      medical records of 230 of the patients, of whom 98 (43%) had unknown transmission
      route, were studied regarding the occurrence of neonatal blood transfusions. The
      clinical, virologic, and histopathologic characteristics of those found to have
      received transfusions as neonates were also studied. RESULTS: Four of 230 (1.7%;
      95% confidence interval, 0.5%-4.4%) patients with hepatitis C had received blood
      products as neonates. Three of them had reported unknown transmission route. One
      had cirrhosis, while two had mild histopathologic findings on liver biopsy. Three
      out of four patients in the transfused group, including the patient with liver
      cirrhosis, had undergone treatment for hepatitis C, all of them with a sustained
      viral response. CONCLUSION: Previously unidentified neonatal blood transfusions
      explain only a small fraction of chronic hepatitis C cases with unknown
      transmission route. Individual patients infected early in life can develop
      progressive liver damage as young adults and may benefit from antiviral
      treatment. The finding suggests that efforts are needed to actively trace and
      test adults who have been subjected to neonatal blood product transfusion before
      1992.

PMID- 24898458
TI  - Mesenchymal stem or stromal cells: a review of clinical applications and
      manufacturing practices.
AB  - Mesenchymal stem cells (MSCs) have recently generated great interest in the
      fields of regenerative medicine and immunotherapy due to their unique biologic
      properties. In this review we attempt to provide an overview of the current
      clinical status of MSC therapy, primarily focusing on immunomodulatory and
      regenerative or tissue repair applications of MSCs. In addition, current
      manufacturing is reviewed with attention to variation in practices (e.g.,
      starting material, approach to culture and product testing). There is
      considerable variation among the 218 clinical trials assessed here; variations
      include proposed mechanisms of action, optimal dosing strategy, and route of
      administration. To ensure the greatest likelihood of success in clinical trials
      as the field progresses, attention must be given to the optimization of MSC
      culture. 

PMID- 24898466
TI  - [Religious/spiritual well-being in mentally ill persons III: first results of a
      body-centered awareness meditation for in-patient rehabilitation].
AB  - OBJECTIVE: In recent years, positive effects of religiosity and spirituality on
      mental health can be found as well documented in the literature. However, very
      few studies have examined the effects of a spiritually based therapeutic
      intervention among psychiatric patients. METHOD: For this reason, in this pilot
      study we examined the effectiveness of a morning body-centered meditation in
      comparison to a conventional morning walk in regards to subjective well-being and
      stress coping styles in 44 (26 females) randomly assigned psychiatric in-patients
      (according to ICD 10). The patients' amount of subjective well-being as well as
      their coping ability was assessed at the beginning and at the end of a 6 weeks
      therapy. RESULTS: Thereby we found a significant increase in Religious/Spiritual
      Well-Being, Awareness and more adequate Coping strategies. This was paralleled by
      a decrease of psychiatric symptoms. Overall the general assumption of a positive
      association between spirituality and mental health was affirmed. However, we did
      not find any differences between the two treatment methods (meditation vs.
      morning walk). CONCLUSIONS: Both interventions showed the same positive efficacy.
      Based on these initial results, possibilities and boundaries for the integration
      of religious/spiritual issues into the treatment of psychiatric patients are
      discussed.

PMID- 24898467
TI  - Association of vitamin D receptor Fok1 (rs2228570), TaqI (rs731236) and ApaI
      (rs7975232) gene polymorphism with the risk of chronic kidney disease.
AB  - Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of
      chronic kidney disease (CKD) from the published reports are still conflicting.
      This study was conducted to evaluate the relationship between VDR Fok1
      (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk
      of CKD using meta-analysis method. The association studies were identified from
      PubMed and Cochrane Library on 1 March 2014, and eligible investigations were
      included and synthesized using meta-analysis method. Five reports were recruited
      into this meta-analysis for the association of VDR Fok1, TaqI and ApaI gene
      polymorphism with CKD susceptibility. In this meta-analysis, VDR Fok1, TaqI and
      ApaI gene polymorphism were not associated with CKD susceptibility for overall
      populations and in Caucasians. However, the Fok1 f allele, ff genotype and FF
      genotype were associated with the risk of CKD in Asians. In conclusion, VDR Fok1,
      TaqI and ApaI gene polymorphism were not associated with CKD risk in overall
      populations and in Caucasians. But, the Fok1 gene polymorphism was associated
      with the risk of CKD in Asians. However, more studies should be conducted to
      confirm it. 

PMID- 24898468
TI  - Electrochemical discrimination of phthalic acid among three phthalic acid isomers
      based on an N-butylaminomethyl-ferrocene derivative.
AB  - A chemosensor compound (1) consisting of a central ferrocene with two
      butylaminomethyl arms showed unexpected facile electrochemical oxidation of the
      secondary amines in proximity to the ferrocene, which was utilized for
      electrochemical discrimination of phthalic acid selectively over two other
      isomers, isophthalic acid and terephthalic acid.

PMID- 24898469
TI  - Detection of anti-cytokine antibodies and their clinical relevance.
AB  - Cytokines regulate many aspects of cell growth and differentiation and play
      pivotal roles in the orchestration of immune defence against invading pathogens.
      Though 'self' proteins, they are potentially immunogenic and can give rise to
      anti-cytokine autoantibodies (aCA). The main foci of the article are a critical
      summary of the various methodologies applied for detecting and measuring aCA and
      a broad review of studies of the occurrence, characterization and clinical
      relevance of aCA in normal healthy individuals, patients with autoimmune diseases
      or microbial infections and aCA in patients whose disease is treated with
      recombinant cytokine products. The need for technical and methodological
      improvement of assays, including validation and standardization, together with
      approaches to harmonize calculation and reporting of results is also discussed. 

PMID- 24898472
TI  - Asynchronous hatching in the burying beetle, Nicrophorus quadripunctatus,
      maxmizes parental fitness.
AB  - Life history theory predicts that natural selection favours parents who balance
      investment across offspring to maximize fitness. Theoretical studies have shown
      that the optimal level of parental investment from the offspring's perspective
      exceeds that of its parents, and the disparity between the two generates
      evolutionary conflict for the allocation of parental investment. In various
      species, the offspring hatch asynchronously. The age hierarchy of the offspring
      usually establishes competitive asymmetries within the brood and determines the
      allocation of parental investment among offspring. However, it is not clear
      whether the allocation of parental investment determined by hatching pattern is
      optimal for parent or offspring. Here, we manipulated the hatching pattern of the
      burying beetle Nicrophorus quadripunctatus to demonstrate the influence of
      hatching pattern on the allocation of parental investment. We found that the
      total weight of a brood was largest in the group that mimicked the natural
      hatching pattern, with the offspring skewed towards early hatchers. This
      increases parental fitness. However, hatching patterns with more later hatchers
      had heavier individual offspring weights, which increases offspring fitness, but
      this hatching pattern is not observed in the wild. Thus, our study suggests that
      the natural hatching pattern optimizes parental fitness, rather than offspring
      fitness.

PMID- 24898473
TI  - Guidelines, online training aim to teach physicians to weigh costs of care,
      become better stewards of medical resources.

PMID- 24898470
TI  - Reassignment of scattered emission photons in multifocal multiphoton microscopy.
AB  - Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously
      scanning multiple foci across different regions of specimen. The use of imaging
      detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to
      noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly
      recovered using multianode photomultiplier tubes (MAPMT). In this design,
      however, emission photons scattered to neighbor anodes are encoded by the foci
      scan location resulting in ghost images. The crosstalk between different anodes
      is currently measured a priori, which is cumbersome as it depends specimen
      properties. Here, we present the photon reassignment method for MMM, established
      based on the maximum likelihood (ML) estimation, for quantification of crosstalk
      between the anodes of MAPMT without a priori measurement. The method provides the
      reassignment of the photons generated by the ghost images to the original spatial
      location thus increases the SNR of the final reconstructed image. 

PMID- 24898471
TI  - Efficacy and safety of fesoterodine 8 mg in subjects with overactive bladder
      after a suboptimal response to tolterodine ER.
AB  - AIMS: To assess fesoterodine 8 mg efficacy over time and vs. placebo in subjects
      with overactive bladder (OAB) who responded suboptimally to tolterodine extended
      release (ER) 4 mg. METHODS: In a 12-week, double-blind trial, subjects with self
      reported OAB symptoms for >= 6 months, mean of >= 8 micturitions and >= 2 to < 15
      urgency urinary incontinence (UUI) episodes/24 h, and suboptimal response to
      tolterodine ER 4 mg (defined as <= 50% reduction in UUI episodes during 2-week
      run-in) were randomised to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks) or
      placebo once daily. Change from baseline to week 12 in UUI episodes (primary end
      point) was analysed in step-wise fashion: first, baseline vs. week 12 for
      fesoterodine; if significant, then change from baseline to week 12 for
      fesoterodine vs. placebo. RESULTS: By week 12, subjects receiving fesoterodine 8
      mg had significantly greater improvement from baseline vs. placebo in UUI
      episodes, urgency episodes and scores on the Patient Perception of Bladder
      Control, Urgency Perception Scale and OAB Questionnaire Symptom Bother and Health
      Related Quality of Life scales and domains (all p < 0.05). 50% and 70% UUI
      responder rates were also significantly higher with fesoterodine 8 mg vs. placebo
      at week 12 (p < 0.05). Dry mouth (placebo, 4%, 12/301; fesoterodine, 16.6%,
      51/308) and constipation (placebo, 1.3%, 4/301; fesoterodine, 3.9%, 12/308) were
      the most frequent adverse events. CONCLUSIONS: Subjects who responded
      suboptimally to tolterodine ER 4 mg showed significant improvements in UUI and
      other OAB symptoms and patient-reported outcomes, with good tolerability, during
      treatment with fesoterodine 8 mg vs. placebo.

PMID- 24898474
TI  - Role of IL-17 and TGF-beta in peritoneal adhesion formation after surgical
      trauma.
AB  - Peritoneal adhesions are fibrous tissues formed after surgery. Both cytokines and
      transforming growth factors (TGFs) are involved in this process. The objective of
      this study was to investigate the cross talk between these entities. Peritoneal
      drainage fluid after surgery from patients and rodent models was examined by
      enzyme-linked immunosorbent assay and fluorescence-activated cell sorter. Data
      showed that the concentrations of interferon (IFN)-gamma and interleukin (IL)-17
      reached their peaks 6-12 hours after surgery, whereas TGF-beta1 concentrations
      showed two postoperative peak time points at 2 and 72-96 hours. By neutralizing
      IFN-gamma, IL-17 6-12 hours, and TGF-beta1 72-96 hours after surgery, the degree
      of adhesion reduced significantly. However, neutralizing TGF-beta1 2 hours after
      surgery did not affect adhesion formation. Furthermore, in vitro studies showed
      that compared with the fibroblasts that were directly stimulated with TGF-beta1,
      the prestimulation of IL-17 promoted plasminogen activator inhibitor-1 production
      while inhibiting tissue-type plasminogen activator production. Moreover,
      additional stimulation with IFN-gamma enhanced this effect. Together, these data
      indicate that IL-17 may promote adhesion formation by increasing the reaction of
      fibroblasts against TGF-beta1. Blocking IL-17 might have a therapeutic potential
      in preventing adhesion formation after surgery. 

PMID- 24898475
TI  - Involvement of Caveolin-1 in CD83 Internalization in Mouse Dendritic Cells.
AB  - To become potent T-cell stimulators, DCs need to mature. Treatment with soluble
      CD83 (sCD83) induces immune tolerance and protects against transplant rejection
      by maintaining dendritic cells in an immature, tolerogenic state. Until now, the
      mechanism through which sCD83 keeps DCs immature has not been investigated. The
      internalizing pathway of CD83 was screened by Western blot, and the direct
      interactions between internalized proteins were verified through
      coimmunoprecipitation (co-IP) and transmission electron microscopy (TEM). CD83
      plasma membrane levels were detected by Western blot using a plasma membrane
      protein extraction protocol. The changes in CD83 surface levels in DCs were
      detected by flow cytometry. Caveolin-1 function was detected in a kidney
      transplant model. In this study, we demonstrated that caveolin-1 could affect
      CD83 level during endocytosis in mouse DCs. Caveolin-1 coprecipitates with CD83,
      as demonstrated by co-IP analysis. TEM morphometric analysis of the entire CD83
      distribution associated with internalized caveolin-1 demonstrated a significant
      interaction in cellular vesicles. sCD83 reduces endogenous CD83 plasma membrane
      levels, and caveolin-1 knockdown reverts CD83 levels in plasma membrane. sCD83
      treatment decreases CD83 surface levels in DCs. siRNA to caveolin-1 in DCs
      inhibits this effect of sCD83. The effects of sCD83-treated DCs were proved in
      CD1 mice. Knocking down caveolin-1 in DCs obstructs the effects of sCD83 on
      kidney transplant. In conclusion, our data indicated that a caveolin-dependent
      endocytic pathway is involved in CD83 internalization in DCs and that caveolin-1
      is involved in the activity of DCs. 

PMID- 24898476
TI  - Harnessing mechanobiology of human pluripotent stem cells for regenerative
      medicine.
AB  - Recent advances in human pluripotent stem cells (hPSCs) open new doors for
      therapeutics of motor neuron (MN)-associated neurodegenerative diseases. However,
      the MN differentiation process is not yet completely understood. In this
      Viewpoint, we stress the concept of designing synthetic cell culture surfaces
      with precisely controlled mechanical properties (such as rigidity) to improve the
      efficiency of MN differentiation from hPSCs. Emerging evidence strongly supports
      the potent role of mechanobiology in controlling stem cell fate. Leveraging the
      intrinsic mechanosensitive properties of hPSCs in conjunction with a synthetic
      elastomeric micropost array system, we have recently demonstrated significantly
      improved MN differentiation from hPSCs. Mechanotransduction mechanisms of hPSCs
      are an unexplored territory and likely involve coordination and cross-regulations
      of multiple targets and pathways including cell surface receptors, signaling
      transduction molecules, and nuclear proteins. We envision that research in hPSCs
      for MN degenerative diseases will benefit from accumulating knowledge of
      mechanobiology of hPSCs. 

PMID- 24898477
TI  - An automated minimum retest interval rejection rule reduces repeat CRP workload
      and expenditure, and influences clinician-requesting behaviour.
AB  - AIMS: Repeat serum C-reactive protein (CRP) measurements on the same day or on
      consecutive days are of limited clinical value. Minimum retesting intervals are
      recommended for managing unnecessary repeat testing. As not previously reported,
      we studied the effect of minimum retesting interval test rejection on laboratory
      workload and expenditure and on clinician-requesting behaviour. METHODS: In a
      prospective study, we evaluated the effect of an automated 48 h CRP minimum
      retesting interval rule on inpatient and outpatient CRP workload and costs.
      Control data on inpatient and outpatient serum urea and electrolytes (UE)
      workload were collected during the study. RESULTS: Over 1 year, there was a 7.0%
      and 12.3% decrease in CRP requests and CRP tests analysed, respectively,
      following the introduction of the minimum retesting interval rule when compared
      to the 1 year baseline period. This equated to an estimated annual reduction in
      revenue costs of L10 500, but cash savings in consumable costs of L3000. There
      was no significant change in UE requests. CONCLUSIONS: We report, for the first
      time, that automated minimum retesting interval rejection rules as a stand-alone
      strategy are a cheap and sustainable method for reducing unnecessary repeat CRP
      tests, resulting in small laboratory cash savings, more efficient use of
      laboratory resources and standardisation of patient care pathways. The minimum
      retesting interval rejection rule also altered clinician test-requesting
      behaviour towards more appropriate requesting.

PMID- 24898478
TI  - Probing molecular interaction in ionic liquids by low frequency spectroscopy:
      Coulomb energy, hydrogen bonding and dispersion forces.
AB  - Ionic liquids are defined as salts composed solely of ions with melting points
      below 100  degrees C. These remarkable liquids have unique and fascinating
      properties and offer new opportunities for science and technology. New
      combinations of ions provide changing physical properties and thus novel
      potential applications for this class of liquid materials. To a large extent, the
      structure and properties of ionic liquids are determined by the intermolecular
      interaction between anions and cations. In this perspective we show that far
      infrared and terahertz spectroscopy are suitable methods for studying the cation
      anion interaction in these Coulomb fluids. The interpretation of the measured low
      frequency spectra is supported by density functional theory calculations and
      molecular dynamics simulations. We present results for selected aprotic and
      protic ionic liquids and their mixtures with molecular solvents. In particular,
      we focus on the strength and type of intermolecular interaction and how both
      parameters are influenced by the character of the ions and their combinations. We
      show that the total interaction between cations and anions is a result of a
      subtle balance between Coulomb forces, hydrogen bonds and dispersion forces. For
      protic ionic liquids we could measure distinct vibrational modes in the low
      frequency spectra indicating clearly the cation-anion interaction characterized
      by linear and medium to strong hydrogen bonds. Using isotopic substitution we
      have been able to dissect frequency shifts related to pure interaction strength
      between cations and anions and to different reduced masses only. In this context
      we also show how these different types of interaction may influence the physical
      properties of ionic liquids such as the melting point, viscosity or enthalpy of
      vaporization. Furthermore we demonstrate that low frequency spectroscopy can also
      be used for studying ion speciation. Low vibrational features can be assigned to
      contact ion pairs and solvent separated ion pairs. In conclusion we showed how
      detailed knowledge of the low frequency spectra can be used to understand the
      change in interaction strength and structure by variation of temperature, solvent
      polarity and solvent concentration in ionic liquids and their mixtures with
      molecular solvents. In principle the used combination of methods is suitable for
      studying intermolecular interaction in pure molecular liquids and their solutions
      including additive materials such as nanoparticles. 

PMID- 24898480
TI  - Molecular structures of tris(2-mercapto-1-tert-butylimidazolyl)hydroborato and
      tris(2-mercapto-1-adamantylimidazolyl)hydroborato sodium complexes: analysis of
      [Tm(R)] ligand coordination modes and conformations.
AB  - The tris(mercaptoimidazolyl)hydroborato complexes, [kappa(3)-S2H
      Tm(Bu(t))]Na(THF)3 and [kappa(3)-S2H-Tm(Ad)]Na(THF)3, which feature t-butyl and
      adamantyl substituents, have been synthesized via the reactions of the respective
      1-R-1,3-dihydro-2H-imidazole-2-thiones with NaBH4 in THF (R = Bu(t), 1-Ad). X-ray
      diffraction studies indicate that the compounds are monomeric and that the
      [Tm(R)] ligands coordinate to the metal in a kappa(3)-S2H manner via two of the
      sulfur donors and the hydrogen attached to boron, a combination that is
      unprecedented for sodium derivatives. Analysis of the
      tris(mercaptoimidazolyl)hydroborato compounds that are listed in the Cambridge
      Structural Database has allowed for the formulation of a set of criteria that
      enables kappa(x)-S(x) and kappa(x+1)-S(x)H coordination modes to be identified.
      Furthermore, the various kappa(x)-S(x) and kappa(x+1)-S(x)H coordination modes
      have also been analyzed with respect to the conformations of the [Tm(R)] ligands,
      which differ by rotation of the imidazolethione moieties about the B-N bond.

PMID- 24898479
TI  - Expression of p53, Ki67, EcPV2- and EcPV3 DNA, and viral genes in relation to
      metastasis and outcome in equine penile and preputial squamous cell carcinoma.
AB  - REASONS FOR PERFORMING STUDY: Equine penile and preputial squamous cell carcinoma
      (SCC) is a potentially lethal disease of which little is known regarding the
      relationship between tumour characteristics and prognosis. OBJECTIVES: To assess
      the relationship between tumour differentiation grade (tumour subtype), presence
      of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53
      and Ki67 and metastasis in equine penile and preputial SCC and to assess the
      relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67
      with survival. STUDY DESIGN: Retrospective case-control study using archived
      material. METHODS: Samples (n = 103) from 87 horses with penile and/or preputial
      intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files
      were evaluated. Tumours were graded microscopically and p53 and Ki67 expression
      evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA
      was detected by conventional PCR. Real-time PCR was used for quantification of
      E2, E6 and L1 mRNA. RESULTS: Equine papillomavirus type 2 DNA was detected in
      89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of
      E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and
      occurrence of metastasis were positively correlated to a less differentiated
      subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences
      in survival between subtypes were significant (log Rank P<0.001); horses with
      less differentiated tumours were more likely to die of the disease (papilloma
      8.3%; G1 26.1%; G2 26.3%; G3 63.3%). CONCLUSIONS: In equine penile and preputial
      SCC, tumour grading is an important prognosticator for survival and a predictor
      for presence of metastases. Expression of p53 and Ki67 and presence or expression
      of EcPV2 and EcPV3 do not appear to be important prognosticators.

PMID- 24898481
TI  - A prospective study of midfoot osteotomy combined with adjacent joint sparing
      internal fixation in treatment of rigid pes cavus deformity.
AB  - BACKGROUND: Midfoot osteotomy has been previously confirmed to be a good method
      to correct pes cavus. How to fix the osteotomy and which point to choose for the
      procedure has been a focus for most surgeons. The aim of this study was to
      analyse the outcomes of a series of patients who had been treated for pes cavus
      deformity using midfoot osteotomy combined with adjacent joint sparing internal
      fixation. MATERIALS AND METHODS: Between 2008 and 2012, 17 patients with a mean
      age of 16.8 years (12-36 years) were tracked after treatment by midfoot osteotomy
      combined with adjacent joint sparing internal fixation with three cannulated
      screws between the Lisfranc line and Cyma line. Clinical outcomes were assessed
      by measuring improvements of appearance and function, American Orthopedic Foot
      and Ankle Society (AOFAS) scores, and radiographic changes. RESULTS: The mean
      follow-up time was 25.3 months (range, 10-50). The mean healing time from the
      osteotomy was 7.8 weeks (range, 6-12). The appearance and weight-bearing function
      were significantly improved in all patients. At a final follow-up, the mean AOFAS
      score was 75.8/100 points (range, 63-90). The mean Meary's angle, calcaneal pitch
      angle, tibiotalar angle, and Hibb's angle values improved from 26.3 to 5.5, 44.5
      to 28.3, 133.1 to 100.8 and 66.9 to 41.1, respectively. Adjacent joints presented
      no obviously arthritic degeneration at the follow-up. Subjectively, 94.1% of
      patients were very satisfied or satisfied with minor reservations. Objective
      outcomes were excellent or good in 88.2% of feet. CONCLUSION: For the treatment
      of rigid pes cavus deformity, extra-articular midfoot osteotomy combined with
      adjacent joint sparing internal fixation is effective and safe. This surgical
      technique is especially effective with low rates of arthritic degeneration and
      joint stiffness in the adjacent joints and little reduction of ankle and foot
      flexibility.

PMID- 24898483
TI  - [Present states and prospects of functional dyspepsia].

PMID- 24898484
TI  - [Recent mechanistic insights into the pathogenesis of functional dyspepsia:
      focusing on interoceptive system].

PMID- 24898482
TI  - Curricular factors associated with medical students' practice of the skin cancer
      examination: an educational enhancement initiative by the integrated skin exam
      consortium.
AB  - IMPORTANCE: As medical school curricula become progressively integrated, a need
      exists to optimize education related to the skin cancer examination (SCE) for
      melanoma, a relevant competency gap that influences secondary prevention efforts.
      OBJECTIVES: To identify curricular factors associated with medical students'
      confidence, intent, and performance regarding the SCE. DESIGN, SETTING, AND
      PARTICIPANTS: Survey-based cross-sectional study from the Integrated Skin Exam
      Consortium at accredited US medical schools among a volunteer sample of second
      year students representing 8 geographically varied public and private
      institutions. Students were administered a questionnaire to assess
      characteristics, curricular exposures, and educational and practical experiences
      related to skin cancer, as well as knowledge of melanoma risk and a detection
      method. MAIN OUTCOMES AND MEASURES: Primary outcomes were confidence in
      performing the SCE, intent to perform an integrated skin examination, and actual
      performance of the SCE. RESULTS: Physical diagnosis session and clinical
      encounter were most predictive of confidence in performance of the SCE (odds
      ratios [ORs], 15.35 and 11.48, respectively). Other curricular factors associated
      with confidence included instruction time of at least 60 minutes on skin cancer
      (OR, 6.35), lecture on the SCE (OR, 7.54), knowledge of melanoma risk (OR, 3.71),
      and at least 1 opportunity to observe the SCE (OR, 2.70). Physical diagnosis
      session and at least 4 opportunities to observe the SCE were most predictive of
      intent to perform an integrated skin examination (ORs, 4.84 and 4.72,
      respectively). Other curricular factors associated with intent included knowledge
      of melanoma risk (OR, 1.83), clinical encounter (OR, 2.39), and at least 1
      opportunity to observe the SCE (OR, 1.95). Clinical encounter, physical diagnosis
      session, and at least 1 opportunity to observe the SCE were most predictive of
      performance of the SCE (ORs, 21.67, 15.48, and 9.92, respectively). Other
      curricular factors associated with performance included instruction time of at
      least 60 minutes on skin cancer (OR, 2.42) and lecture on the SCE (OR, 5.04).
      CONCLUSIONS AND RELEVANCE: To augment the practice of the SCE among medical
      students, course directors may design an integrated curriculum that includes at
      least 60 minutes of instruction related to melanoma and the SCE, a description of
      the integrated skin examination as part of the physical diagnosis course, and
      education on high-risk demographic groups and anatomic sites specific to men and
      women and on the ABCDEs of melanoma, and at least 1 opportunity to observe the
      SCE.

PMID- 24898485
TI  - [Gastrointestinal motility disorders of functional dyspepsia].

PMID- 24898486
TI  - [Rome III classification and characteristics of Japanese patients with functional
      dyspepsia].

PMID- 24898487
TI  - [Association between functional and Helicobacter pylori-related dyspepsia].

PMID- 24898488
TI  - [Two cases of dabigatran-induced esophageal ulcer indicating the usefulness of
      drug administration guidance].
AB  - Here we report two cases of dabigatran-induced esophageal ulcer. Case 1 was a 67
      year-old man who presented with heartburn that developed a month after dabigatran
      administration. Case 2 was an 81-year-old woman who presented with epigastralgia
      that developed within a few days of dabigatran administration. Endoscopic
      findings were similar in both cases, including shallow esophageal ulcers covered
      with a thin whitish membrane. The patients were advised to consume the drug with
      plenty of water during meals and to remain in a sitting position for 30 min after
      consumption. This method successfully decreased their symptoms and ulcers,
      indicating that drug administration guidance is extremely effective in managing
      dabigatran-induced esophageal injury.

PMID- 24898489
TI  - [A case of superficial esophageal basaloid squamous cell carcinoma resected by
      endoscopic submucosal dissection].
AB  - A woman in her 70s visited our hospital to undergo endoscopy.
      Esophagogastroduodenoscopy showed a white submucosal tumor-like lesion in the
      upper esophagus. Analysis of a biopsy specimen revealed that the tumor was a
      basaloid squamous cell carcinoma. A superficial squamous cell carcinoma was also
      revealed near the basaloid squamous cell carcinoma before endoscopic submucosal
      dissection. Curative en bloc resection was successfully performed.
      Histopathological examination revealed that the basaloid and superficial squamous
      cell carcinomas had invaded the lamina propria (pT1a-LPM) and epithelium (pT1a
      EP), respectively. In addition, the basaloid squamous cell carcinoma had two
      different components in terms of malignancy and differentiation. Here we report a
      rare case of esophageal basaloid squamous cell carcinoma resected by endoscopic
      submucosal dissection. 

PMID- 24898490
TI  - [A case of advanced gastric cancer with an invasive micropapillary carcinoma
      component].
AB  - A 62-year-old man was admitted for the evaluation of epigastric pain. Upper
      gastrointestinal endoscopy revealed a type 3 circumferential carcinoma in the
      gastric antrum. Distal gastrectomy was performed, and the lesion was
      histopathologically diagnosed as gastric cancer with an invasive micropapillary
      carcinoma component. Chemotherapy was administered after surgery; however, he
      died with multiple liver metastases after 39 months. Micropapillary carcinoma is
      a rare, high-grade, malignant histological subtype of gastric cancer that has not
      been described in detail till date. Here we describe this rare lesion and present
      a review of the relevant literature. 

PMID- 24898491
TI  - [A case of intraventricular dissemination arising from hepatocelullar carcinoma
      effectively treated with intrathecal administration of methotrexate].
AB  - A 78-year-old man with hepatocellular carcinoma was admitted to our hospital for
      vertigo after transcatheter arterial chemoembolization. Contrast-enhanced
      magnetic resonance imaging revealed metastasis in the cerebellar vermis. Although
      the cerebellar metastasis decreased in size after cyberknife radiotherapy,
      multiple enhancing nodules appeared in the cerebral ventricles. A diagnosis of
      intraventricular dissemination from the cerebellar metastatic lesion originating
      from the hepatocellular carcinoma was made. Six intrathecal administrations of 20
      mg of methotrexate through lumbar puncture resulted in a dramatic decrease in the
      intraventricular dissemination. Although intraventricular dissemination recurred
      4 months later, these lesions disappeared after an additional 8 administrations
      of intrathecal methotrexate. Intraventricular dissemination arising from
      hepatocellular carcinoma is rare. Here we report a case that was successfully
      treated by intrathecal chemotherapy with methotrexate. 

PMID- 24898492
TI  - [A case of hepatocellular carcinoma complicated by pleural effusion mixed with
      bile after radiofrequency ablation].
AB  - An 84-year-old Japanese man was admitted with hepatocellular carcinoma (HCC). He
      underwent transcatheter arterial chemoembolization and percutaneous
      radiofrequency ablation (RFA). Three weeks later, he developed sudden-onset right
      pleural effusion mixed with bile. Drip infusion cholangiography-computed
      tomography revealed leakage of the contrast agent, which passed from the HCC to
      the pleural cavity through a perforation in the diaphragm. The patient's
      condition improved after thoracic and endoscopic nasobiliary drainage. The
      occurrence of pleural effusion mixed with bile is a rare complication of RFA.
      This case provides important information about the morbidity, prevention, and
      treatment of this complication. 

PMID- 24898493
TI  - [Submucosal bacterial abscesses of the ascending colon and liver associated with
      portal and superior mesenteric vein thrombosis due to Enterococcus faecalis
      infection: a case report].
AB  - A 72-year-old woman with diabetes mellitus was admitted with fever and general
      fatigue. Blood biochemistry showed elevated hepatic and biliary enzyme levels,
      abdominal computed tomography showed multiple liver abscesses with portal and
      superior mesenteric vein thrombosis, and total colonoscopy revealed a submucosal
      bacterial abscess in the ascending colon. The abscesses were determined to be
      associated with Enterococcus faecalis infection. The patient was treated
      conservatively with antibiotics (meropenem) and anticoagulants (warfarin), which
      led to a gradual amelioration of symptoms and resolution of thrombosis. 

PMID- 24898494
TI  - [Acute hepatitis C infection with prolonged intrahepatic cholestasis and
      remarkable progression of fibrosis mimicking fibrosing cholestatic hepatitis].
AB  - We report the case of a 71-year-old woman with acute hepatitis C infection and
      persistent viremia since 2 years. Her clinical course was characterized by
      general fatigue and prolonged jaundice with unusually high serum bilirubin
      levels. Liver histology showed lymphocyte infiltration, marked fibrosis, and
      severe cholestasis in the periportal zone, findings mimicking fibrosing
      cholestatic hepatitis (FCH). Fibrosing cholestatic hepatitis is a life
      threatening form of recurrent hepatitis C infection that typically occurs in
      immunosuppressed patients. Here we report the rare case of an immunocompetent
      patient who developed this condition. 

PMID- 24898495
TI  - [Liver injury and hepatic encephalopathy induced by the herbal medicine
      Hochuekkito].
AB  - A 57-year-old man was admitted with pruritus and jaundice following treatment for
      fatigue with the herbal medicine Hochuekkito. The patient was prescribed
      prednisolone and ursodeoxycholic acid, but he developed progressive cholestasis
      that required intravenous methylprednisolone pulse therapy. After treatment with
      plasma exchange for prolonged prothrombin time, the patient recovered; however,
      his liver function deteriorated because of liver injury induced by trimethoprim
      sulfamethoxazole for pneumocystis pneumonia. After reduction of trimethoprim
      sulfamethoxazole, his liver function almost returned to normal by day 130 of
      admission. It has remained normal for 10 months since then. Therefore, when
      prescribing Hochuekkito, the possibility of drug-induced liver injury should be
      taken in account. 

PMID- 24898496
TI  - The role of site-directed point mutations in protein misfolding.
AB  - A self-consistent mean-field based model is presented to explore the role of site
      directed point mutations in designing folded and/or misfolded sequences with a
      reduced hydrophobic-polar (HP) patterning of amino acids. This site-directed
      point mutation procedure is developed and applied to both real and lattice
      proteins to generate a diverse set of sequences. The respective roles of core and
      surface residues are analyzed with respect to the optimum hydrophobicity required
      for the structural stability of the protein. The core sites are found to have a
      critical number of hydrophobic residues, below which a protein may misfold, while
      the surface sites show a clear preference for the polar residues with the ability
      to tolerate some hydrophobic residues. Although core sites play an important role
      in the structural stability of proteins, some specific surface sites are also
      found to be equally important. A clash and match calculation procedure is
      proposed, which may be used to predict the number of residue pairs in a sequence
      with unfavorable and favorable interactions, respectively, due to site-directed
      point mutations. The number of clashing and matching residue pairs may indicate
      whether the mutated sequence would be folded or misfolded. The results are
      independent of the secondary structure topology of the protein. This model may
      provide new insights into the effect of point mutations on protein stability and
      may introduce a new method to predict the outcome of a mutation in terms of its
      probability to fold or misfold. 

PMID- 24898497
TI  - Groundwater app to determine flow direction and gradient.
AB  - A computational program, called the groundwater flow calculator, was created to
      quickly and easily determine the hydraulic gradient and direction of groundwater
      flow. The groundwater flow calculator automates the hand-drawn process by Ralph
      Heath in the U.S. Geological Survey (USGS) Water Supply Paper 2220. In addition,
      a mobile app was developed to allow this procedure to run on a smart phone for
      use in the field. 

PMID- 24898499
TI  - ADAM metalloproteases promote a developmental switch in responsiveness to the
      axonal repellant Sema3A.
AB  - During embryonic development, axons can gain and lose sensitivity to guidance
      cues, and this flexibility is essential for the correct wiring of the nervous
      system. Yet, the underlying molecular mechanisms are largely unknown. Here we
      show that receptor cleavage by ADAM (A Disintegrin And Metalloprotease)
      metalloproteases promotes murine sensory axons loss of responsiveness to the
      chemorepellant Sema3A. Genetic ablation of ADAM10 and ADAM17 disrupts the
      developmental downregulation of Neuropilin-1 (Nrp1), the receptor for Sema3A, in
      sensory axons. Moreover, this is correlated with gain of repulsive response to
      Sema3A. Overexpression of Nrp1 in neurons reverses axonal desensitization to
      Sema3A, but this is hampered in a mutant Nrp1 with high susceptibility to
      cleavage. Lastly, we detect guidance errors of proprioceptive axons in ADAM
      knockouts that are consistent with enhanced response to Sema3A. Our results
      provide the first evidence for involvement of ADAMs in regulating developmental
      switch in responsiveness to axonal guidance cues. 

PMID- 24898501
TI  - Substituted diphenyl butadiynes: a computational study of geometries and
      electronic transitions using DFT/TD-DFT.
AB  - This work is aimed at theoretical understanding of electronic absorption and
      emission energies of a series of substituted diphenyl butadiynes through an
      assessment of several TDDFT functionals and a detailed study of solvent effects
      on their ground and excited state structures and properties. Out of a series of
      functionals examined, the coulomb attenuated DFT functional CAM-B3LYP is found to
      be most successful in predicting charge transfer absorption and emission energies
      of such derivatives. However, TDDFT potential energy surfaces obtained from
      hybrid functionals such as B3LYP and PBE0 are found to give a good description of
      the stability of locally excited (LE) and intramolecular charge transfer (ICT)
      states as a function of torsional angle, for the butadiynyl fluorophores.
      Interesting structural variations are observed in the ground and excited state
      optimized geometries of the fluorophores. The ICT emission of the butadiynyl
      fluorophores is observed to originate from the twisted state where the two phenyl
      rings in the diphenyl butadiyne get twisted around the butadiyne moiety. A
      bending of the butadiyne moiety is noted for some of the butadiynyl derivatives
      in the ICT emissive state. In addition, the direction of absorption and emission
      transition dipole moment vectors of the butadiynyl fluorophores is found to
      depend on the nature of substituents present at the periphery of the diphenyl
      butadiyne moiety. 

PMID- 24898502
TI  - [Rare diseases are common].

PMID- 24898500
TI  - Biotechnological strategies to improve production of microbial poly-(3
      hydroxybutyrate): a review of recent research work.
AB  - Poly-(3-hydroxybutyrate) [P(3HB)] is a polyester synthesized as a carbon and
      energy reserve material by a wide number of bacteria. This polymer is
      characterized by its thermo-plastic properties similar to plastics derived from
      petrochemical industry, such as polyethylene and polypropylene. Furthermore,
      P(3HB) is an inert, biocompatible and biodegradable material which has been
      proposed for several uses in medical and biomedical areas. Currently, only few
      bacterial species such as Cupriavidus necator, Azohydromonas lata and recombinant
      Escherichia coli have been successfully used for P(3HB) production at industrial
      level. Nevertheless, in recent years, several fermentation strategies using other
      microbial models such as Azotobacter vinelandii, A. chroococcum, as well as some
      methane-utilizing species, have been developed in order to improve the P(3HB)
      production and also its mean molecular weight. 

PMID- 24898503
TI  - [The many facets of inherited skin fragility].
AB  - The inherited skin fragility encompasses a heterogeneous group of disorders,
      collectively designated as epidermolysis bullosa, characterized by recurrent
      mechanically induced blisters, erosions or wounds. The spectrum of clinical
      manifestations is broad, as well as the molecular background. Besides the skin,
      mucosal membranes and other organs can be affected. In real-world practice,
      patients with mild genetic skin fragility usually do not require medical care and
      often remain underdiagnosed. In contrast, the well-defined severe EB subtypes are
      recognized based on typical clinical features. The molecular diagnostics is
      usually performed in order to allow genetic counselling and prenatal diagnosis.
      Besides wound care and careful management of the disease complications, new
      experimental targeted therapies are being developed. New very rare forms of
      inherited skin fragility have been identified with modern sequencing methods. 

PMID- 24898505
TI  - [Alterations in nails and teeth as a clue for genodermatoses].
AB  - BACKGROUND: There are about 10,000 monogenic diseases and around 30% demonstrate
      alterations in the skin and its appendages. As there are so many genetic
      different skin diseases, clear diagnosis is often very difficult. AIM: The goal
      of this review is to give the clinicians some key features on nails and teeth
      which might help to identify rare genodermatoses. DISCUSSION: In the daily work
      genodermatoses manifest more commonly as incomplete or oligosymptomatic syndromes
      than as complete symptom complexes. To diagnose a rare disorder in such
      situations, a knowledge of key features which are characteristic for a
      genodermatoses is essential, so that a diagnosis can be advanced and the
      underlying gene defect identified. Changes in nails and teeth sometimes may be
      useful as diagnostic key features. Both structures originate from ectoderm and
      therefore they often appear in combination in diseases with major ectodermal
      malformations. Enamel defects resembling the lines of Blaschko are highly
      suggestive for focal dermal hypoplasia, even if other important signs and
      symptoms are missing. Enamel defects combined with gingival fibromas are highly
      suggestive for tuberous sclerosis. On the other side, triangular lunulae with
      malformation and dystrophy of the nail plate suggests nail-patella syndrome.

PMID- 24898504
TI  - [Palmoplantar dermatoses: when should genes be considered?].
AB  - BACKGROUND: Palmoplantar dermatoses are common. They can be both functionally
      debilitating and markedly stigmatize the patient because they are so visible.
      Dermatoses on the hands and feet often go along with palmoplantar hyperkeratosis.
      Such palmoplantar keratoses (PPK) can be classified into acquired (non
      hereditary) and hereditary (monogenetic) PPK. OBJECTIVES: A considerable
      proportion of PPK develop on the grounds of gene defects. As these diseases
      constitute a heterogeneous group of quite uncommon single entities, the treating
      physician must know when to entertain the diagnosis of a hereditary PPK and which
      causative genes should be considered. METHODS: We summarize the common causes of
      acquired and hereditary PPK based on a review of the latest literature. RESULTS:
      The most common causes of acquired PPK are inflammatory dermatoses like
      psoriasis, lichen planus, or hand and feet eczema. Also irritative-toxic (arsenic
      poisoning, polycyclic aromatic hydrocarbons) and infectious causes of PPK (human
      papilloma viruses, syphilis, scabies, tuberculosis, mycoses) are not uncommon.
      Genetically caused PPK may occur isolated, within syndromes or as a
      paraneoplastic marker. The clinical/histological classification discerns diffuse,
      focal, or punctuate forms of PPK with and without epidermolysis. A new
      classification based on the causative gene defect is starting to replace the
      traditional clinical classification. CONCLUSIONS: Knowledge about the large, but
      heterogeneous group of hereditary PPK is important to adequately counsel and
      treat patients and their families.

PMID- 24898506
TI  - [Alopecia and hypotrichosis in childhood: clinical features and diagnosis].
AB  - The monogenic inherited isolated alopecias comprise a group of clinically and
      genetically heterogeneous disorders with decreased or absent hair. Clinical
      classification of the isolated alopecias is based upon the onset of the disorder,
      the regions affected, and the structure of the hair shaft. Men and women are
      equally affected, and the mode of inheritance is autosomal dominant or autosomal
      recessive. Therapy does not exist for these rare forms of alopecia. However,
      molecular genetic diagnosis is possible for the identification of the genetic
      causes and for the specification of the recurrence risk. Since the identification
      of the keratin gene KRT86 as a cause of the so called monilethrix in 1997,
      mutations in eleven other genes have been identified for various isolated
      alopecias. These include other keratin genes for monilethrix, the HR gene for
      atrichia congenita, the genes CDSN, APCDD1 and SNRPE for the autosomal dominant
      form of hypotrichosis simplex, and the genes DSG4, LIPH and LPAR6 for the
      autosomal recessive forms of hypotrichosis as well as U2HR for hypotrichosis type
      Marie Unna. Molecular genetic and pathophysiological studies of these rare
      disorders of hair development have significantly contributed to our understanding
      of the basic mechanisms of hair loss as well as the physiological mechanisms of
      hair growth.

PMID- 24898507
TI  - [Genodermatoses with malignant skin tumors].
AB  - Cutaneous malignancies can manifest as isolated and sporadic tumors as well as
      multiple and disseminated tumors. In the latter case they often point to a
      genetic disease, which either can be restricted to the skin exclusively or also
      involve extracutaneous organs in the context of a hereditary tumor syndrome. Such
      hereditary tumor syndromes are clinically and genetically very heterogeneous.
      Therefore, the prevailing specific skin tumors play an important diagnostic role
      in the case of complex symptom constellations. Elucidation of the genetic basis
      of rare monogenetically inherited disorders and syndromes can contribute to a
      better understanding of the pathogenesis of frequently occurring cutaneous
      malignancies because the mutated genes often encode proteins, which have a key
      position in metabolic signaling pathways that are of high significance for the
      development of targeted therapies. Here we provide an overview of genodermatoses,
      which are associated with basal cell carcinomas, sebaceous carcinomas,
      keratoacanthomas, squamous cell carcinomas and malignant melanomas. 

PMID- 24898508
TI  - [How frequently does genetic mosaicism occur in the skin?].
AB  - BACKGROUND: Until recently, cutaneous mosaicism was considered a rare phenomenon.
      Its practical significance was considered minimal. OBJECTIVES: The following
      questions will be considered: How often are mosaic skin disorders seen in
      dermatological practice? In which ways can special dermatological competence
      contribute to assure an appropriate genetic counseling? METHODS: This review is
      based on the analysis of recent research articles and on the author's book
      "Mosaicism in Human Skin" (Berlin, Springer 2014). RESULTS: The following
      categories can be distinguished: punctual versus disseminated mosaicism;
      segmental manifestation of lethal autosomal mutations; type 1 versus type 2
      segmental involvement in autosomal dominant skin disorders; isolated versus
      superimposed manifestation of polygenic skin disorders; twin spotting; epigenetic
      mosaicism; revertant mosaicism. CONCLUSIONS: Cutaneous mosaicism occurs so
      frequently that dermatologists can note it every day in their practice, usually
      in the form of punctual mosaicism. In the group of autosomal dominant
      genodermatoses, the type 1 segmental manifestation implies a slightly increased
      risk that the disorder will affect the patient's offspring in a diffuse form,
      whereas in cases of type 2 segmental involvement this risk is 50%. In the group
      of common skin disorders with a polygenic background, cellular analysis of a
      superimposed segmental manifestation may contribute to elucidate the genetic
      basis of such diseases. In the group of epigenetically controlled functional
      mosaics of the skin, we discriminate between X-linked and autosomal forms that
      are always inheritable. From the concept of revertant mosaicism, a new approach
      to treat severe genodermatoses can perhaps be developed.

PMID- 24898509
TI  - [Multiple blue nodules].

PMID- 24898510
TI  - [Debating histamine intolerance: are adverse reactions to histamine-containing
      foods fact or fiction?].
AB  - Low-histamine diets are very popular and often self-imposed among people
      suspecting histamine intolerance. Most of these diets avoid a huge variety of
      foods containing more or less histamine, which has a considerable impact on their
      quality of life, but in most cases no long-term benefit. Underlying a diminished
      capacity for histamine degradation, the lack of partial or complete symptom
      improvement might be due to the fact that endogenous histamine release could also
      be responsible for symptoms. The role of ingested histamine-below the level for
      intoxication-is discussed controversially. However, it is obvious that the
      histamine content of a certain food alone is not enough to predict its tolerance.
      If histamine intolerance is suspected, an individual diagnostic and therapeutic
      procedure is mandatory in order to minimize avoidance and to preserve a high
      quality of life. Ideally this is done in a close cooperation between allergists
      and nutritionists. 

PMID- 24898511
TI  - Expression of obesity-related miR-1908 in human adipocytes is regulated by
      adipokines, free fatty acids and hormones.
AB  - White adipose tissue mass is governed by competing processes that control lipid
      synthesis and storage, as well as the development of new adipocytes, and also
      trigger metabolic and inflammatory changes. microRNAs (miRNAs) have been
      suggested to act as negative regulators controlling varied biological processes
      at the level of post-transcriptional repression. The present study focused on
      investigating the expression of miR-1908 in mature human adipocytes and its
      responses to adipokines [tumor necrosis factor alpha (TNF-alpha), interleukin 6
      (IL-6), leptin and resistin), free fatty acids (FFAs), growth hormone (GH) and
      dexamethasone (DEX). miR-1908 was highly expressed in mature human adipocytes.
      The mature human adipocytes responded to proinflammatory cytokines (TNF-alpha and
      IL-6) by markedly increasing the expression of miR-1908 at 4 h of incubation.
      Adipokines (resistin and leptin) and FFAs were shown to downregulate the
      expression of miR-1908 in human adipocytes. Furthermore, the expression of miR
      1908 was decreased 4 h after treatment with GH; however, DEX treatment of human
      adipocytes did not affect the expression of miR-1908 during the 24-h experimental
      period. In conclusion, the present study showed that the expression of miR-1908
      is affected by a variety of factors that are associated with obesity and insulin
      sensitivity. miR-1908 may be an important mediator in the development of obesity
      related complications. 

PMID- 24898513
TI  - TERT promoter mutation as an early genetic event activating telomerase in
      follicular thyroid adenoma (FTA) and atypical FTA.
AB  - BACKGROUND: The telomerase reverse transcriptase (TERT) promoter mutations C228T
      and C250T have been found in many malignancies, including in thyroid carcinomas.
      However, it is unclear how early these mutations occur in thyroid tumorigenesis.
      METHODS: The study included primary tumors from 58 patients initially diagnosed
      with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA
      (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid
      carcinoma (FTC). Sanger sequencing was used to investigate the mutational status
      of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression
      were determined using quantitative polymerase chain reaction (PCR). Telomerase
      activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay
      kit. RESULTS: The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18
      AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase
      activity, whereas the majority of C228T-negative adenomas lacked TERT expression
      (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS
      gene mutations (P = .016). The patient with C228T-mutated FTA later developed a
      scar recurrence and died of FTC, whereas none of the remaining 57 patients with
      FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried
      C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%)
      exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of
      the mutation was associated with shorter patient survival. CONCLUSIONS: TERT
      promoter mutations may occur as an early genetic event in thyroid follicular
      tumors that have not developed malignant features on routine histopathological
      workup.

PMID- 24898514
TI  - Bis- and tris(pyrazolyl)borate/methane-stabilized P(III) -centered cations.
AB  - We report the synthesis of [H2 B(pz)2 PR](+) , [H2 C(pz)2 PR](+2) , [HB(pz)3
      P](+2) , and [HC(pz)3 P](+3) (H2 B(pz)2 =bis(pyrazolyl)borate; H2 C(pz)2
      =bis(pyrazolyl)methane; HB(pz)3 =tris(pyrazolyl)borate; HC(pz)3 =tris(pyrazolyl)
      methane; R=Ph, Cy or Et2 N) by reaction of the corresponding neutral or anionic
      ligands with chlorophosphines in the presence of TMSOTf. The structures of these
      compounds were determined by X-ray crystallographic analysis and the nature of
      their bonding was examined using density functional theory. 

PMID- 24898512
TI  - A prominent role for invariant T cells in the amphibian Xenopus laevis tadpoles.
AB  - Invariant T (iT) cells expressing an invariant or semi-invariant T cell receptor
      (TCR) repertoire have gained attention in recent years because of their potential
      as specialized regulators of immune function. These iT cells are typically
      restricted by nonclassical MHC class I molecules (e.g., CD1d and MR1) and undergo
      differentiation pathways distinct from conventional T cells. While the benefit of
      a limited TCR repertoire may appear counterintuitive in regard to the advantage
      of the diversified repertoire of conventional T cells allowing for exquisite
      specificity to antigens, the full biological importance and evolutionary
      conservation of iT cells are just starting to emerge. It is generally considered
      that iT cells are specialized to recognize conserved antigens equivalent to
      pathogen-associated molecular pattern. Until recently, little was known about the
      evolution of iT cells. The identification of class Ib and class I-like genes in
      nonmammalian vertebrates, despite the heterogeneity and variable numbers of these
      genes among species, suggests that iT cells are also present in ectothermic
      vertebrates. Indeed, recent studies in the amphibian Xenopus have revealed a
      drastic overrepresentation of several invariant TCRs in tadpoles and identified a
      prominent nonclassical MHC class I-restricted iT cell subset critical for tadpole
      antiviral immunity. This suggests an important and perhaps even dominant role of
      multiple nonclassical MHC class I-restricted iT cell populations in tadpoles and,
      by extension, other aquatic vertebrates with rapid external development that are
      under pressure to produce a functional lymphocyte repertoire with small numbers
      of cells. 

PMID- 24898515
TI  - Laparoscopic Morgagni hernia repair: how I do it.
AB  - Surgical repair of Morgagni hernias is recommended given their historically high
      risk of incarceration. Traditionally, such repair has been undertaken via
      laparotomy or thoracotomy or more recently, thoracoscopically or laparoscopically
      using mesh. Here, we describe a laparoscopic approach to the management of
      Morgagni hernias achieving a primary tissue repair without mesh implantation.
      This technique allows for the general benefits of minimally invasive surgery,
      such as less postoperative pain, reduced wound complications, decreased duration
      of the hospital stay, as well as offering an alternative to mesh implantation and
      its associated potential complications. 

PMID- 24898516
TI  - Perioperative outcome after pancreatic head resection: a 10-year series of a
      specialized surgeon in a university hospital and a community hospital.
AB  - INTRODUCTION: Hospital and surgeon volume are potential factors influencing
      postoperative mortality and morbidity after pancreatic resection. Data on
      perioperative outcome of individual surgeons in different institutions, however,
      are scarce. We evaluated the perioperative outcome after pancreatic head
      resections (PHR) performed by a high-volume pancreatic surgeon in a high-volume
      university department and (later) in a community hospital with low prior
      experience in major pancreatic surgery. METHODS: We compared the results after
      PHR were performed by a single experienced surgeon between 2001 and October 2006
      in a specialized unit of a German university hospital (n = 83; group A) with the
      results after PHR were performed in a community hospital between November 2006
      and 2011 (n = 145; group B). Before the study period (-2001), the surgeon already
      had a personal caseload of >200 PHR. In addition to the 228 PHR analyzed here,
      the surgeon also had taught further >150 PHR to residents and consulting
      surgeons. Comparable surgical and perioperative techniques were applied in both
      series (e.g., types of resection and reconstruction, abdominal drains, early
      enteral feeding). The data of both series were prospectively recorded in SPSS
      databases. RESULTS: The median age of the patients was lower in group A (58 vs.
      66 years in B; p < 0.01). Indications for PHR were pancreatic cancer (A 39 % vs.
      B 45 %), other periampullary cancer (A 18 % vs. B 12 %), chronic pancreatitis (A
      33 % vs. B 28 %), and others (A 10 % vs. B 15 %). Most PHR were pylorus
      preserving (64 vs. 75 %), with oncologically indicated portal vein resections in
      24 % (A) or 33 % (B). The percentage of duodenum-preserving PHR was lower in
      group B (14 vs. 26 % in A). Mortality of PHR was 3.6 % in group A and 2.8 % in B
      (p = 0.72). Overall morbidity rate was 49 % (A) or 57 % (B; p = 0.25). Using the
      expanded Accordion classification, complications classified as grade 4 or higher
      occurred in 9 % (A) and 11 % (B; p = 0.74). Postoperative pancreatic leak (any
      grade) was documented in 26 % (A) and 25 % (B; p = 0.87). CONCLUSIONS: Surgeon
      volume and a high individual experience, respectively, contribute to acceptable
      complication rates and low mortality rates after pancreatic head resection. An
      experienced surgeon can provide a good perioperative outcome after pancreatic
      resection even after a change of hospital or medical staff.

PMID- 24898517
TI  - Syringobulbia associated with posterior fossa meningioma: a review of the
      literature.
AB  - PURPOSE: Syringomyelia can be defined as a degenerative, progressive and chronic
      spinal cord disease. Its association with tumors of the posterior cranial fossa
      (PCF) is a rare condition. METHODS: The authors report a rare case of
      syringobulbia consequent to a meningioma originating from PCF in a 17-year-old
      female, discussing the pathogenetic mechanism of development and the resolution
      of the syrinx cavity after surgical procedure. RESULTS: The postoperative period
      was uneventful without complications. At 6-month follow-up, MRI revealed complete
      tumor removal with resolution of the syrinx cavity. CONCLUSIONS: In cases of
      syringomyelia and tonsillar herniation associated with PCF meningioma, the tumor
      resection allows to eliminate the mass effect and increases the size of the
      posterior fossa with the progressive ascent of the cerebellar tonsils and the
      consequent reduction of their downward movement with systolic pulsation. The re
      establishment of a normal anatomical condition led to the gradual disappearance
      of syrinx and hydrocephalus.

PMID- 24898519
TI  - Comparison of elemental and black carbon measurements during normal and heavy
      haze periods: implications for research.
AB  - Studies specifically addressing the elemental carbon (EC)/black carbon (BC)
      relationship during the transition from clean-normal (CN) air quality to heavy
      haze (HH) are rare but have important health and climate implications. The
      present study, in which EC levels are measured using a thermal-optical method and
      BC levels are measured using an optical method (aethalometer), provides a
      preliminary insight into this issue. The average daily EC concentration was 3.08
      +/- 1.10 MUg/m(3) during the CN stage but climbed to 11.77 +/- 2.01 MUg/m(3)
      during the HH stage. More importantly, the BC/EC ratio averaged 0.92 +/- 0.14
      during the CN state and increased to 1.88 +/- 0.30 during the HH state. This
      significant increase in BC/EC ratio has been confirmed to result partially from
      an increase in the in situ light absorption efficiency (sigmaap) due to an
      enhanced internal mixing of the EC with other species. However, the exact
      enhancement of sigmaap was unavailable because our monitoring scheme could not
      acquire the in situ absorption (bap) essential for sigmaap calculation. This
      reveals a need to perform simultaneous measurement of EC and bap over a time
      period that includes both the CN and HH stages. In addition, the sensitivity of
      EC to both anthropogenic emissions and HH conditions implies a need to
      systematically study how to include EC complex (EC concentration, OC/EC ratio,
      and sigmaap) as an indicator in air quality observations, in alert systems that
      assess air quality, and in the governance of emissions and human behaviors.

PMID- 24898520
TI  - Evaluating environmental performance using new process capability indices for
      autocorrelated data.
AB  - Traditionally, the process capability index is developed by assuming that the
      process output data are independent and follow normal distribution. However, in
      most environmental cases, the process data are autocorrelated. The autocorrelated
      process, if unrecognized as an independent process, can lead to erroneous
      decision making and unnecessary quality loss. In this paper, three new capability
      indices with unbiased estimators are proposed to relieve the independence
      assumption for the-nominal-the-best and the-smaller-the-better cases.
      Furthermore, we use mean squared error (MSE) and mean absolute percent error
      (MAPE) to compare the accuracy of our proposed indices to previous autocorrelated
      indices. The results show that our proposed capability indices outperform the
      predecessors. 

PMID- 24898522
TI  - Age and size at maturity in Indonesian women: a norm of reaction?
AB  - OBJECTIVES: We test (McIntyre and Kacerosky's [2011]: Am J Hum Biol 23:305-312)
      prediction that the relationship between age at menarche and height switches from
      negative to positive, in a unidirectional and smooth manner, as the society
      industrializes. According to this prediction, a mid-level industrial country
      should exhibit a weak relationship between the two variables. METHODS: The 8,013
      observations are extracted from the Indonesian Family Life Survey, a nationally
      representative survey. Indonesia is an intermediate case that exists between the
      small-scale agrarian societies and industrialized societies examined by McIntyre
      and Kacerosky. While age at menarche is a recalled and self-reported variable,
      height is a measured one. The relationship is informally provided in a figure and
      formally estimated using ordinary least squares (OLS). RESULTS: The informal
      finding clearly shows no relationship between age at menarche and height. The OLS
      results also agree that the relationship is very weak. Specifically, despite the
      large sample size, the relationship is not statistically significant in a linear
      manner, regardless of whether the outlier group (age at menarche 10) is included
      or excluded. Various robustness checks are performed to confirm this finding.
      CONCLUSIONS: Our results lend support to McIntyre and Kacerosky's explanation as
      to why the relationship between age at menarche and height switches from negative
      to positive as the society industrializes. Furthermore, our results imply that
      the model (the Day and Rowe model) and theory (life history theory) on which this
      explanation is based are plausible.

PMID- 24898518
TI  - Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor
      cells in a viral model of multiple sclerosis.
AB  - Transplantation of major histocompatibility complex-mismatched mouse neural
      precursor cells (NPCs) into mice persistently infected with the neurotropic JHM
      strain of mouse hepatitis virus (JHMV) results in rapid rejection that is
      mediated, in part, by T cells. However, the contribution of the innate immune
      response to allograft rejection in a model of viral-induced neurological disease
      has not been well defined. Herein, we demonstrate that the natural killer (NK)
      cell-expressing-activating receptor NKG2D participates in transplanted allogeneic
      NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from
      C57BL/6 (H-2(b) ) mice express the NKG2D ligand retinoic acid early precursor
      transcript (RAE)-1 but expression was dramatically reduced upon differentiation
      into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated
      killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of
      C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d) ) mice resulted in
      infiltration of NKG2D(+) CD49b(+) NK cells and treatment with blocking antibody
      specific for NKG2D increased survival of allogeneic NPCs. Furthermore,
      transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected
      BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D/RAE
      1 signaling axis in allograft rejection. We also demonstrate that transplantation
      of allogeneic NPCs into JHMV-infected mice resulted in infection of the
      transplanted cells suggesting that these cells may be targets for infection.
      Viral infection of cultured cells increased RAE-1 expression, resulting in
      enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these
      results show that in a viral-induced demyelination model, NK cells contribute to
      rejection of allogeneic NPCs through an NKG2D signaling pathway.

PMID- 24898521
TI  - Glacier moraine formation-mimicking colloidal particle assembly in
      microchanneled, bioactive hydrogel for guided vascular network construction.
AB  - This study demonstrates that a new method to align microparticles releasing
      bioactive molecules in microchannels of a hydrogel allows the guiding of growth
      direction and spacing of vascular networks. 

PMID- 24898523
TI  - 'This doctor, I not trust him, I'm not safe': the perceptions of mental health
      and services by unaccompanied refugee adolescents.
AB  - BACKGROUND: Unaccompanied refugee adolescents are a small but clinically
      significant group. This group is vulnerable with physical and psychiatric needs
      which are often not met. There are several barriers to providing care for this
      group, originating with the refugees but also due to service provision. AIMS: The
      aim of this research is to appreciate the views and perceptions that
      unaccompanied minors hold about mental health and services. METHOD: Fifteen
      unaccompanied adolescents engaged with mental health services were interviewed,
      and thematic analysis was employed to explore relevant issues. DISCUSSION: Their
      views reflected a range of opinions on mental health and the treatments they
      received, but many held negative attitudes toward mental health and had a lack of
      trust in services. This could be explained by their descriptions of their
      experiences within their home country of psychiatric care, their experiences of
      being a refugee/asylum-seeker or cultural differences. CONCLUSION: We argue it is
      important to engage this group in the development of policy and practice in child
      mental health, and in developing services.

PMID- 24898524
TI  - Oxidative stress predicts progression of peripheral and cardiac autonomic nerve
      dysfunction over 6 years in diabetic patients.
AB  - Oxidative stress is implicated in the pathogenesis of experimental diabetic
      neuropathy, but prospective studies in diabetic patients are lacking. We aimed to
      evaluate whether the plasma levels of various biomarkers of oxidative stress
      predict the progression of diabetic neuropathy and mortality over 6 years. We
      followed 89 diabetic patients aged 54 +/- 14 years (59 % with polyneuropathy), 72
      of whom underwent nerve function reassessment after 6.2 +/- 0.8 years, whereas 17
      died after 4.2 +/- 1.0 years. Plasma markers of oxidative stress at baseline
      included superoxide anion, hypochlorous acid, peroxynitrite, 8-iso-prostaglandin
      F2alpha, vitamin E/lipid ratio, and vitamin C. Neuropathy was assessed by
      symptoms and deficits, motor and sensory nerve conduction velocity (MNCV, SNCV),
      vibration perception thresholds (VPT), thermal detection thresholds, and heart
      rate variability (HRV). Despite a reduction in HbA1c by 1.4 +/- 1.6 % (p <
      0.001), median SNCV, sural SNCV, peroneal MNCV, malleolar VPT, and warm TDT
      deteriorated after 6 years (all p < 0.05). In multivariate models, increased
      superoxide generation was associated with a decline in median SNCV (beta = 
      0.997; p = 0.036) and deterioration in HRV at rest (OR 1.63 [95 % CI 1.09-2.44];
      p = 0.017) over 6 years. Low vitamin E/lipid ratio tended to predict a decrease
      in peroneal MNCV (beta = 0.781; p = 0.057) and an increase in malleolar VPT (beta
      = -0.725; p = 0.077). Plasma superoxide generation was associated with an
      increased risk of mortality (HR 23.2 [95 % CI 1.05-513]; p = 0.047). In
      conclusion, increased plasma superoxide generation predicted the decline in
      sensory and cardiac autonomic nerve function and mortality over 6 years in
      diabetic patients, but larger studies are required for confirmation.

PMID- 24898525
TI  - An antimicrobial stewardship program's real-world experience with fidaxomicin for
      treatment of Clostridium difficile infection: a case series.
AB  - STUDY OBJECTIVE: To evaluate real-world clinical and economic outcomes in
      patients with Clostridium difficile infection (CDI) treated with fidaxomicin.
      DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: A
      total of 61 patients with CDI who were treated with fidaxomicin monotherapy or
      combination therapy from September 2011 to December 2012. MEASUREMENTS AND MAIN
      RESULTS: Data on demographics, infection characteristics, and clinical and
      economic outcomes were evaluated. Clinical cure was defined as resolution of
      diarrhea (less than or equal to three unformed stools for at least 2 consecutive
      days) maintained for the duration of therapy with no further requirement for CDI
      therapy and was achieved in 44 (72.1%) patients. Clinical cure was significantly
      higher for patients receiving fidaxomicin monotherapy compared with fidaxomicin
      combination therapy (25/29 [86.2%] patients vs 19/32 [59.4%] patients, p=0.04).
      Clinical cure was similar in patients with a first or prior CDI episode (65.5% vs
      78.1%, p=0.27) and in patients with severe versus nonsevere disease (68.4% vs
      73.8%, p=0.66). Recurrence occurred in 6 (13.6%) of the 44 patients who achieved
      clinical cure. Mortality attributable to CDI was 11.5%, and 30-day readmission
      rate was 4.9%. Median cost accrued during CDI was $19,483/patient. CONCLUSION:
      Our real-world experience with fidaxomicin significantly differs from the
      findings of phase III clinical trials. Fidaxomicin is also associated with
      substantial costs. Multicenter studies are needed to determine the optimal role
      of fidaxomicin in the treatment of CDI.

PMID- 24898526
TI  - Axonal and dendritic localization of mRNAs for glycogen-metabolizing enzymes in
      cultured rodent neurons.
AB  - BACKGROUND: Localization of mRNAs encoding cytoskeletal or signaling proteins to
      neuronal processes is known to contribute to axon growth, synaptic
      differentiation and plasticity. In addition, a still increasing spectrum of mRNAs
      has been demonstrated to be localized under different conditions and developing
      stages thus reflecting a highly regulated mechanism and a role of mRNA
      localization in a broad range of cellular processes. RESULTS: Applying
      fluorescence in-situ-hybridization with specific riboprobes on cultured neurons
      and nervous tissue sections, we investigated whether the mRNAs for two metabolic
      enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key
      enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it
      were so, this might contribute to clarify the so far enigmatic role of neuronal
      glycogen. We found that the mRNAs for both enzymes are localized to axonal and
      dendritic processes in cultured lumbar spinal motoneurons, but not in cultured
      trigeminal neurons. In cultured cortical neurons which do not store glycogen but
      nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and
      dendritic localization. In spinal motoneurons and trigeminal neurons in situ,
      however, the mRNAs could only be demonstrated in the neuronal somata but not in
      the nerves. CONCLUSIONS: We could demonstrate that the mRNAs for major enzymes of
      neural energy metabolism can be localized to neuronal processes. The
      heterogeneous pattern of mRNA localization in different culture types and
      developmental stages stresses that mRNA localization is a versatile mechanism for
      the fine-tuning of cellular events. Our findings suggest that mRNA localization
      for enzymes of glycogen metabolism could allow adaptation to spatial and temporal
      energy demands in neuronal events like growth, repair and synaptic transmission.

PMID- 24898527
TI  - What factors influence applicants' rankings of orthopaedic surgery residency
      programs in the National Resident Matching Program?
AB  - BACKGROUND: In accordance with the American Academy of Orthopaedic Surgeons'
      strategic goal of enriching our field by building a more diverse orthopaedic
      workforce, the specialty needs further information delineating the factors
      important to the applicant pool as a whole and more specifically to women and
      other underrepresented minority groups. QUESTIONS/PURPOSES: This study aims to
      identify (1) factors important to residency applicants selecting an orthopaedic
      residency program; (2) differences in factor importance for men, women, and
      minorities, and (3) the importance of different information sources used when
      making his or her rank list. METHODS: All 742 applicants who applied to the
      authors' orthopaedic surgery residency program in the 2013 National Resident
      Matching Program were queried. The response rate was 28% (207 of 742).
      Respondents were asked to rank, on a 5-point Likert scale, 37 factors that may
      have affected their rank lists to differing degrees. Respondents also identified
      the importance of sources of information used to make their rank lists, factors
      that residency programs considered important when ranking applicants, and their
      level of agreement with various sex- and racial-specific statements regarding
      orthopaedic training. RESULTS: The most important factors affecting rank lists
      were perceived happiness/quality of life of current residents, resident
      camaraderie, and impression after an away rotation. Women weighed their personal
      interactions and a program's proximity to family and friends more heavily when
      determining a rank list. Sixty-eight percent of women eliminated residency
      programs from their options based on perceived sex biases versus less than 1% of
      men. Applicants valued information obtained from away rotations at an institution
      and in talking with current residents most when determining his or her rank list.
      CONCLUSIONS: Programs should consider interpersonal factors, like quality of life
      and resident camaraderie as factors in attracting applicants. They also should
      minimize perceived biases and emphasize interactions with current residents
      during the application process to meet their goals of attracting an exceptional
      and more diverse orthopaedic workforce.

PMID- 24898528
TI  - Long-term followup of surgically treated knee dislocations: stability restored,
      but arthritis is common.
AB  - BACKGROUND: Surgical treatment of knee dislocations is intended to correct the
      anatomic injury and restore knee stability and patient function. Several studies
      have shown successful results with surgical treatment of knee dislocations with
      up to 10 years of followup, but longer-term studies are uncommon.
      QUESTIONS/PURPOSES: We evaluated patients treated surgically for knee
      dislocations at 10-year followup to assess (1) knee stability; (2) return to
      preinjury level of function; (3) development of arthrosis; and (4) range of
      motion (ROM) loss. METHODS: This study was a retrospective review of 127 combined
      PCL, ACL, and medial and/or lateral side reconstructions performed by a single
      surgeon (GCF) between 1990 and 2008. Of these, 44 were available for clinical and
      functional evaluation (35%) at a minimum 5-year followup. Inclusion criteria were
      combined PCL/ACL plus medial and/or lateral side reconstruction. Evaluation
      methods included arthrometer measurements, stress radiography, knee ligament
      rating and activity scales (Lysholm and Tegner), plain radiographs with
      osteoarthritic assessment, and physical examination. RESULTS: Of the 44 patients,
      there were nine ACL/PCL medial, 22 ACL/PCL lateral, and 13 ACL/PCL mediolateral
      reconstructions. Followup was at a minimum of 5 years (mean, 10 years; range, 5
      22 years). The mean age at the time of injury was 31 years with a range of 13 to
      65 years. The mean arthrometer-measured side-to-side differences were as follows:
      PCL screen, 1.9 mm; corrected posterior, 2.4 mm; corrected anterior, 0.8 mm; and
      anterior displacement at 30 degrees  of knee flexion, 1.7 mm. Stress radiographic
      measurements at 90 degrees  of knee flexion revealed a mean side-to-side
      difference of 1.9 mm. Mean Lysholm, and Tegner scores were 84 of 100 and 4.1 of
      9, respectively. Ninety-three percent (41 of 44) of patients returned to their
      preinjury level of activity or one Tegner grade lower. Ten of the 44 knees (23%)
      developed degenerative joint disease. The mean flexion loss was 12.5 degrees ,
      and flexion contractures were not seen in any of the patients. CONCLUSIONS: We
      found that a high proportion of patients treated for these severe injuries
      achieved static and functional stability, allowing the return to physically
      demanding work and recreational activities, but that nearly one-fourth of them
      will develop arthritis at a mean of 10 years. We cannot extrapolate our results
      to an elite athlete population, but our results probably apply well to working
      class populations. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 24898529
TI  - Reply to the letter to the editor: is stability of the proximal tibiofibular
      joint important in the multiligament-injured knee?

PMID- 24898530
TI  - The risk of revision after TKA is affected by previous HTO or UKA.
AB  - BACKGROUND: High tibial osteotomy (HTO) and unicompartmental arthroplasty (UKA)
      are reconstructive surgeries advocated for younger patients. In case of failure
      or progression of osteoarthritis, they can both be converted to a total knee
      arthroplasty (TKA). QUESTIONS/PURPOSES: We used registry data to answer if the
      risks of revision for TKAs after previous HTOs and UKAs differ and how these
      compare with that of de novo TKAs. Furthermore, we wanted to examine the extent
      of stemmed/revision implants being used for the conversions. METHODS: We
      identified HTOs performed during 1998 to 2007 with the help of the inpatient and
      outpatient care registries of the Swedish National Board of Health and Welfare
      and gathered relevant information from hospital records. The Swedish Knee
      Arthroplasty Register was then examined to find all de novo TKAs, TKAs performed
      after HTO, and TKAs performed after UKA through the end of 2012. RESULTS: For 920
      TKAs after previous UKA and 356 TKAs after previous closed-wedge HTOs, we found
      the risk of revision significantly higher than for the 118,229 de novo TKAs (risk
      ratio, 2.8; confidence interval [CI], 2.2-3.5; p<0.001, and 1.7 CI, 1.1-2.6;
      p<0.001, respectively), whereas for the 482 open-wedge osteotomies, the
      difference was not significant (risk ratio, 1.2; CI, 0.8-1.8; p=0.44). Stemmed
      implants were used in 663 of the 117,566 primary de novo TKAs (0.6%), in 22 of
      the 809 HTO conversions (4%) and in 136 of the 920 UKA conversions (17%).
      CONCLUSIONS: TKAs after previous reconstructive surgery carry an increased risk
      for revision. However, our findings do not mitigate against the use of UKA and
      HTO in selected cases. LEVEL OF EVIDENCE: Level III, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 24898532
TI  - Species delimitation in Trametes: a comparison of ITS, RPB1, RPB2 and TEF1 gene
      phylogenies.
AB  - Trametes is a cosmopolitan genus of white rot polypores, including the "turkey
      tail" fungus, T. versicolor. Although Trametes is one of the most familiar genera
      of polypores, its species-level taxonomy is unsettled. The ITS region is the most
      commonly used molecular marker for species delimitation in fungi, but it has been
      shown to have a low molecular variation in Trametes resulting in poorly resolved
      phylogenies and unclear species boundaries, especially in the T. versicolor
      species complex (T. versicolor sensu stricto, T. ochracea, T. pubescens, T.
      ectypa). Here we evaluate the performance of three protein-coding genes (TEF1,
      RPB1, RPB2) for species delimitation and phylogenetic reconstruction in Trametes.
      We obtained 59 TEF1, 34 RPB1 and 55 RPB2 sequences from 69 individuals, focusing
      on the T. versicolor complex and performed phylogenetic analyses with maximum
      likelihood and parsimony methods. All three protein-coding genes outperformed ITS
      for separating species in the T. versicolor complex. The multigene phylogenetic
      analysis shows the highest amount of resolution and supported nodes separating T.
      ectypa, T. ochracea, T. pubescens and T. versicolor with strong support. In
      addition three slineages are resolved in the species complex of T. elegans. The
      T. elegans complex includes three species: T. elegans (based on material from
      Puerto Rico, Belize, the Philippines), T. aesculi (from North America) and T.
      repanda (from Papua New Guinea, the Philippines, Venezuela). The utility of gene
      markers varies, with TEF1 having the highest PCR and sequencing success rate and
      RPB1 offering the best backbone resolution for the genus. 

PMID- 24898531
TI  - Serenomyces associated with palms in southeastern USA: isolation, culture storage
      and genetic variation.
AB  - Serenomyces is a genus belonging to the family Phaeochoraceae, which is known to
      occur only in association with the plant family Arecaceae (palms). It is presumed
      to be one of the causes of a leaf disease referred to as either rachis blight or
      petiole blight, depending on the palm species affected. The fungus is not readily
      observed, with few reports in the literature; it cannot be readily isolated from
      tissue, with only one known instance of it being cultured on artificial media and
      has no DNA sequences deposited in GenBank. Over an 8 y period, leaves symptomatic
      for rachis or petiole blight were obtained from Florida and South Carolina, USA.
      The fungus was induced to produce ascospores, and single-spore isolates were
      obtained in culture and, in some instances, induced to produce ascospores in
      culture. Based on ascospores size and ITS sequencing, Serenomyces from Phoenix
      canariensis and P. dactylifera form one group, Serenomyces from Thrinax radiata
      form a second group and Serenomyces from Sabal palmetto form a third. All three
      groups are most similar morphologically to Serenomyces phoenicis. Due to the
      observed instability of Serenomyces in culture, we have suggestions regarding the
      storage of this fungus. 

PMID- 24898533
TI  - Genetic analysis of post-pandemic 2010-2011 influenza A(H1N1)pdm09 hemagglutinin
      virus variants that caused mild, severe, and fatal infections in Northern Greece.
AB  - Since its appearance, influenza A(H1N1)pdm09 caused considerable morbidity and
      mortality in Northern Greece. Genetic analysis of post-pandemic circulating
      strains scoped to investigate any correlation between genetic variations that
      emerged during viral evolution and severity of infection. Pharyngeal
      swabs/aspirates (n = 1,870) were examined with real-time reverse transcription
      polymerase chain reaction. Hemagglutinin sequences were analyzed on 110 strains
      (37 fatal/73 non-fatal cases), followed by statistical and phylogenetic analysis.
      Influenza A(H1N1)pdm09 was detected in 848 samples. Coexistence of clusters 3, 4,
      5, 6, and 7 indicated co-circulation of lineages in Northern Greece. Genetic
      analysis showed that HA sequences had 96-99% sequence similarity with the vaccine
      strain and that there was no association between any co-circulating lineage and
      severity. Several viruses accumulated variations in HA antigenic sites. D222G was
      significantly associated with fatal infections, supporting its association with
      increased viral pathogenesis. On the other hand, four variations were associated
      with milder disease outcomes. Certain signature amino acid changes persisted
      during and/or after the pandemic, indicating their offer of selective advantages
      to the virus. Negative selection was observed in 70% of pandemic variations as
      they probably did not contribute to the virus fitness. It is of interest that
      persistent variations were highly identified in the vicinity of antigenic or
      receptor-binding sites. Of those, K171R was associated only with fatal
      infections. Also of interest, only strains that were isolated from fatal
      infections had variations that altered both their acid-base and polarity
      properties. Genetic changes that may alter the antigenicity, pathogenicity and
      transmissibility of circulating virus variants need to be determined and closely
      monitored.

PMID- 24898534
TI  - Metabolic engineering of lactate dehydrogenase rescues mice from acidosis.
AB  - Acidosis causes millions of deaths each year and strategies for normalizing the
      blood pH in acidosis patients are greatly needed. The lactate dehydrogenase (LDH)
      pathway has great potential for treating acidosis due to its ability to convert
      protons and pyruvate into lactate and thereby raise blood pH, but has been
      challenging to develop into a therapy because there are no pharmaceutical-based
      approaches for engineering metabolic pathways in vivo. In this report we
      demonstrate that the metabolic flux of the LDH pathway can be engineered with the
      compound 5-amino-2-hydroxymethylphenyl boronic acid (ABA), which binds lactate
      and accelerates the consumption of protons by converting pyruvate to lactate and
      increasing the NAD(+)/NADH ratio. We demonstrate here that ABA can rescue mice
      from metformin induced acidosis, by binding lactate, and increasing the blood pH
      from 6.7 to 7.2 and the blood NAD(+)/NADH ratio by 5 fold. ABA is the first class
      of molecule that can metabolically engineer the LDH pathway and has the potential
      to have a significant impact on medicine, given the large number of patients that
      suffer from acidosis. 

PMID- 24898537
TI  - Odanacatib treatment affects trabecular and cortical bone in the femur of
      postmenopausal women: results of a two-year placebo-controlled trial.
AB  - Odanacatib, a selective cathepsin K inhibitor, increases areal bone mineral
      density (aBMD) at the spine and hip of postmenopausal women. To gain additional
      insight into the effects on trabecular and cortical bone, we analyzed
      quantitative computed tomography (QCT) data of postmenopausal women treated with
      odanacatib using Medical Image Analysis Framework (MIAF; Institute of Medical
      Physics, University of Erlangen, Erlangen, Germany). This international,
      randomized, double-blind, placebo-controlled, 2-year, phase 3 trial enrolled 214
      postmenopausal women (mean age 64 years) with low aBMD. Subjects were randomized
      to odanacatib 50 mg weekly (ODN) or placebo (PBO); all participants received
      calcium and vitamin D. Hip QCT scans at 24 months were available for 158 women
      (ODN: n = 78 women; PBO: n = 80 women). There were consistent and significant
      differential treatment effects (ODN-PBO) for total hip integral (5.4%),
      trabecular volumetric BMD (vBMD) (12.2%), and cortical vBMD (2.5%) at 24 months.
      There was no significant differential treatment effect on integral bone volume.
      Results for bone mineral content (BMC) closely matched those for vBMD for
      integral and trabecular compartments. However, with small but mostly significant
      differential increases in cortical volume (1.0% to 1.3%) and thickness (1.4% to
      1.9%), the percentage cortical BMC increases were numerically larger than those
      of vBMD. With a total hip BMC differential treatment effect (ODN-PBO) of nearly
      1000 mg, the proportions of BMC attributed to cortical gain were 45%, 44%, 52%,
      and 40% for the total, neck, trochanter, and intertrochanter subregions,
      respectively. In postmenopausal women treated for 2 years, odanacatib improved
      integral, trabecular, and cortical vBMD and BMC at all femur regions relative to
      placebo when assessed by MIAF. Cortical volume and thickness increased
      significantly in all regions except the femoral neck. The increase in cortical
      volume and BMC paralleled the increase in cortical vBMD, demonstrating a
      consistent effect of ODN on cortical bone. Approximately one-half of the absolute
      BMC gain occurred in cortical bone.

PMID- 24898539
TI  - Identification of chromosome instability in Japanese quail (Coturnix japonica).
AB  - 1. A study of the incidence of chromosome instability in the Japanese quail as
      assessed by sister chromatid exchange (SCE) and fragile site identification in
      chromosomes was conducted in two parent breeds and their F1 and F2 generations.
      2. The mean incidence of SCEs was 6.02 +/- 0.45 and the frequency of fragile
      sites was 1.17 +/- 0.79. 3. There were moderately negative correlations of 0.51
      0.64 between chromosome instability and fertility in the F1 and 0.10-0.23 in the
      F2. The hatch of fertilised eggs was negatively correlated with the number of SCE
      in male (0.31) and female (0.33) F1 and was lower in P (0.18 and 0.19,
      respectively), whereas the correlations were similar for the number of fragile
      sites in both generations (0.51-0.62).

PMID- 24898538
TI  - Automated comparison of last hospital main diagnosis and underlying cause of
      death ICD10 codes, France, 2008-2009.
AB  - BACKGROUND: In the age of big data in healthcare, automated comparison of medical
      diagnoses in large scale databases is a key issue. Our objectives were: 1) to
      formally define and identify cases of independence between last hospitalization
      main diagnosis (MD) and death registry underlying cause of death (UCD) for
      deceased subjects hospitalized in their last year of life; 2) to study their
      distribution according to socio-demographic and medico-administrative variables;
      3) to discuss the interest of this method in the specific context of hospital
      quality of care assessment. METHODS: 1) Elaboration of an algorithm comparing MD
      and UCD, relying on Iris, a coding system based on international standards. 2)
      Application to 421,460 beneficiaries of the general health insurance regime
      (which covers 70% of French population) hospitalized and deceased in 2008-2009.
      RESULTS: 1) Independence, was defined as MD and UCD belonging to different trains
      of events leading to death 2) Among the deaths analyzed automatically (91.7%),
      8.5% of in-hospital deaths and 19.5% of out-of-hospital deaths were classified as
      independent. Independence was more frequent in elder patients, as well as when
      the discharge-death time interval grew (14.3% when death occurred within 30 days
      after discharge and 27.7% within 6 to 12 months) and for UCDs other than
      neoplasms. CONCLUSION: Our algorithm can identify cases where death can be
      considered independent from the pathology treated in hospital. Excluding these
      deaths from the ones allocated to the hospitalization process could contribute to
      improve post-hospital mortality indicators. More generally, this method has the
      potential of being developed and used for other diagnoses comparisons across time
      periods or databases.

PMID- 24898540
TI  - The evolutionary origin of the turtle shell and its dependence on the axial
      arrest of the embryonic rib cage.
AB  - Turtles are characterized by their possession of a shell with dorsal and ventral
      moieties: the carapace and the plastron, respectively. In this review, we try to
      provide answers to the question of the evolutionary origin of the carapace, by
      revising morphological, developmental, and paleontological comparative analyses.
      The turtle carapace is formed through modification of the thoracic ribs and
      vertebrae, which undergo extensive ossification to form a solid bony structure.
      Except for peripheral dermal elements, there are no signs of exoskeletal
      components ontogenetically added to the costal and neural bones, and thus the
      carapace is predominantly of endoskeletal nature. Due to the axial arrest of
      turtle rib growth, the axial part of the embryo expands laterally and the
      shoulder girdle becomes encapsulated in the rib cage, together with the inward
      folding of the lateral body wall in the late phase of embryogenesis. Along the
      line of this folding develops a ridge called the carapacial ridge (CR), a turtle
      specific embryonic structure. The CR functions in the marginal growth of the
      carapacial primordium, in which Wnt signaling pathway might play a crucial role.
      Both paleontological and genomic evidence suggest that the axial arrest is the
      first step toward acquisition of the turtle body plan, which is estimated to have
      taken place after the divergence of a clade including turtles from archosaurs.
      The developmental relationship between the CR and the axial arrest remains a
      central issue to be solved in future.

PMID- 24898542
TI  - Multidimensional Approach Toward Spiritual Coping: Construction and Validation of
      the Spiritual Coping Questionnaire (SCQ).
AB  - The aim of the research was to construct the Spiritual Coping Questionnaire
      (SCQ). Two studies have been carried out: the first on the sample of 1,296
      persons facing stressful situations, and the second, on 352 persons undergoing
      alcohol addiction therapy. The first study provided data for PCA and CFA,
      calculation of internal consistency, test-retest reliability and descriptive
      statistics of the questionnaire. The second study allowed the author to verify
      the construct and criterion validity of the tool. The final version of the SCQ is
      composed of 32 items constituting two scales: positive and negative spiritual
      coping. The scale of positive spiritual coping includes four subscales-domains
      (personal, social, environmental and religious), and the scale of negative
      spiritual coping, three subscales (personal, social and religious). The validity
      and reliability of the tool are satisfactory. The questionnaire can be used to
      measure spiritual coping, both among religious and non-religious people. 

PMID- 24898541
TI  - Looking for new treatments of Infantile Colic.
AB  - Infantile colic is a common disturbance occurring in the first three months of
      life. It is a benign condition and one of the main causes of pediatric
      consultation in the early part of life because of its great impact on family
      life. Some pediatricians are prone to undervalue this issue mainly because of the
      lack of evidence based medicine guidelines. Up to now, there is no consensus
      concerning management and treatment. Literature reports growing evidence about
      the effectiveness of dietary, pharmacological, complementary and behavioral
      therapies as options for the management of infantile colic. Dietary approach,
      usually based on the avoidance of cow's milk proteins in breast-feeding mothers
      and bottle-fed infants, more recently has seen the rise of new special formulas,
      such as partially hydrolyzed proteins and low lactose added with prebiotics or
      probiotics: their efficacy needs to be further documented. Investigated
      pharmacological agents are Simethicone and Cimetropium Bromide: the first is able
      to reduce bloating while the second could reduce fussing crying, but it has been
      tested only for severe infantile colic. No other pain relieving agents have been
      proposed until now, but some clinical trials are ongoing for new drugs.There is
      limited evidence supporting the use of complementary and alternative treatments
      (herbal supplements, manipulative approach and acupuncture) or behavioral
      interventions.Recent studies have focused the role of microbiota in the
      pathogenesis of this disturb and so new treatments, such as probiotics, have been
      proposed, but only few strains have been tested.Further investigations are needed
      in order to provide evidence-based guidelines. 

PMID- 24898544
TI  - In this special issue.

PMID- 24898543
TI  - [Prevalence and risk factors of hepatitis C virus infection in patients on
      hemodialysis: results of a Moroccan study].
AB  - INTRODUCTION: Infection with the hepatitis C virus (HCV) is the leading cause of
      chronic hepatitis in patients on hemodialysis. The objective of this study was to
      determine the prevalence of infection with this virus and its main risk factors
      among chronic hemodialysis patients treated at the Mohammed V military teaching
      hospital in Rabat, Morocco. PATIENTS AND METHODS: Retrospective study of 141
      patients with chronic end-stage kidney disease receiving hemodialysis between
      April 2010 and September 2012, including testing for anti-HCV antibodies and HCV
      RNA. RESULTS: The prevalence of HCV assessed by PCR in chronic hemodialysis
      patients treated at our hospital was 12.1%. Risk factors associated with this
      prevalence included duration of hemodialysis and transfusions. CONCLUSION: The
      prevalence of HCV among patients receiving hemodialysis in Morocco is gradually
      declining and the most important risk factors (transfusions and duration of
      hemodialysis) are becoming progressively less important.

PMID- 24898545
TI  - Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary
      embolism. Prevalence of CTEPH after pulmonary embolism.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) has been estimated to occur
      in 0.1-0.5% of patients who survive a pulmonary embolism (PE), but more recent
      prospective studies suggest that its incidence may be much higher. The absence of
      initial haemodynamic evaluation at the time of PE should explain this
      discrepancy. We performed a prospective multicentre study including patients with
      PE in order to assess the prevalence and to describe risk factors of CTEPH.
      Follow-up every year included an evaluation of dyspnea and echocardiography using
      a predefined algorithm. In case of suspected CTEPH, the diagnosis was confirmed
      using right heart catheterisation (RHC). Signs of CTEPH were searched on the
      multidetector computed tomography (CT) and echocardiography performed at the time
      of PE. Of the 146 patients analysed, eight patients (5.4%) had suspected CTEPH
      during a median follow-up of 26 months. CTEPH was confirmed using RHC in seven
      cases (4.8%; 95%CI, 2.3 - 9.6) and ruled-out in one. Patients with CTEPH were
      older, had more frequently previous venous thromboembolic events and more
      proximal PE than those without CTEPH. At the time of PE diagnosis, patients with
      CTEPH had a higher systolic pulmonary artery pressure and at least two signs of
      CTEPH on the initial CT. After acute PE, the prevalence of CTEPH appears high.
      However, initial echocardiography and CT data at the time of the index PE suggest
      that a majority of patients with CTEPH had previously unknown pulmonary
      hypertension, indicating that a first clinical presentation of CTEPH may mimic
      acute PE. 

PMID- 24898547
TI  - Mapping multivalency and differential affinities within large intrinsically
      disordered protein complexes with segmental motion analysis.
AB  - Intrinsically disordered proteins (IDPs) can bind to multiple interaction
      partners. Numerous binding regions in the IDP that act in concert through complex
      cooperative effects facilitate such interactions, but complicate studying IDP
      complexes. To address this challenge we developed a combined fluorescence
      correlation and time-resolved polarization spectroscopy approach to study the
      binding properties of the IDP nucleoporin153 (Nup153) to nuclear transport
      receptors (NTRs). The detection of segmental backbone mobility of Nup153 within
      the unperturbed complex provided a readout of local, region-specific binding
      properties that are usually masked in measurements of the whole IDP. The binding
      affinities of functionally and structurally diverse NTRs to distinct regions of
      Nup153 can differ by orders of magnitudes-a result with implications for the
      diversity of transport routes in nucleocytoplasmic transport. 

PMID- 24898546
TI  - Structural and functional characterization of MERS coronavirus papain-like
      protease.
AB  - BACKGROUNDS: A new highly pathogenic human coronavirus (CoV), Middle East
      respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi
      Arabia and quickly spread to some European countries since September 2012. Until
      15 May 2014, it has infected at least 572 people with a fatality rate of about
      30% globally. Studies to understand the virus and to develop antiviral drugs or
      therapy are necessary and urgent. In the present study, MERS-CoV papain-like
      protease (PLpro) is expressed, and its structural and functional consequences are
      elucidated. RESULTS: Circular dichroism and Tyr/Trp fluorescence analyses
      indicated that the secondary and tertiary structure of MERS-CoV PLpro is well
      organized and folded. Analytical ultracentrifugation analyses demonstrated that
      MERS-CoV PLpro is a monomer in solution. The steady-state kinetic and
      deubiquitination activity assays indicated that MERS-CoV PLpro exhibits potent
      deubiquitination activity but lower proteolytic activity, compared with SARS-CoV
      PLpro. A natural mutation, Leu105, is the major reason for this difference.
      CONCLUSIONS: Overall, MERS-CoV PLpro bound by an endogenous metal ion shows a
      folded structure and potent proteolytic and deubiquitination activity. These
      findings provide important insights into the structural and functional properties
      of coronaviral PLpro family, which is applicable to develop strategies inhibiting
      PLpro against highly pathogenic coronaviruses.

PMID- 24898548
TI  - Study protocol: PoPE-Prediction of Preterm delivery by Electrohysterography.
AB  - BACKGROUND: Traditional methods used for prediction of preterm delivery are
      subjective and inaccurate. The Electrohysterogram (EHG) and in particular the
      estimation of the EHG conduction velocity, is a relatively new promising method
      for detecting imminent preterm delivery. To date the analysis of the conduction
      velocity has relied on visual inspection of the signals. As a next step towards
      the introduction of EHG analysis as a clinical tool, we propose an automated
      method for EHG conduction velocity estimation for both the speed and direction of
      single spike propagation. METHODS/DESIGN: The study design will be an
      observational cohort study. 100 pregnant women, gestational age between 23 + 5
      and 34 weeks, admitted for threatening preterm labor or preterm prelabor rupture
      of membranes, will be included. The length of the cervical canal will be measured
      by transvaginal ultrasound. The EHG will be recorded using 4 electrodes in a
      fixed configuration. Contractions will be detected by analysis of the EHG and
      using an estimation of the intra uterine pressure. In the selected contractions,
      the delays between channels will be estimated by cross-correlation, and
      subsequently, the average EHG conduction velocity will be derived. Patients will
      be classified as labor group and non-labor group based on the time between
      measurement and delivery. The average conduction velocity and cervical length
      will be compared between the groups. The main study endpoints will be
      sensitivity, specificity, and area under the ROC curve for delivery within
      1,2,4,7, and 14 days from the measurement. DISCUSSION: In this study, the
      diagnostic accuracy of EHG conduction velocity analysis will be evaluated for
      detecting preterm labor. Visual and automatic detection of contractions will be
      compared. Planar wave propagation will be assumed for the calculation of the CV
      vector. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07603227.

PMID- 24898550
TI  - Cyclooxygenase-2 polymorphism: another piece in the cardiovascular puzzle.

PMID- 24898549
TI  - Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a
      strategy for cancer therapy.
AB  - Macrophage infiltration has been identified as an independent poor prognostic
      factor in several cancer types. The major survival factor for these macrophages
      is macrophage colony-stimulating factor 1 (CSF-1). We generated a monoclonal
      antibody (RG7155) that inhibits CSF-1 receptor (CSF-1R) activation. In vitro
      RG7155 treatment results in cell death of CSF-1-differentiated macrophages. In
      animal models, CSF-1R inhibition strongly reduces F4/80(+) tumor-associated
      macrophages accompanied by an increase of the CD8(+)/CD4(+) T cell ratio.
      Administration of RG7155 to patients led to striking reductions of CSF
      1R(+)CD163(+) macrophages in tumor tissues, which translated into clinical
      objective responses in diffuse-type giant cell tumor (Dt-GCT) patients.

PMID- 24898551
TI  - Towards better clinical prediction models: seven steps for development and an
      ABCD for validation.
AB  - Clinical prediction models provide risk estimates for the presence of disease
      (diagnosis) or an event in the future course of disease (prognosis) for
      individual patients. Although publications that present and evaluate such models
      are becoming more frequent, the methodology is often suboptimal. We propose that
      seven steps should be considered in developing prediction models: (i)
      consideration of the research question and initial data inspection; (ii) coding
      of predictors; (iii) model specification; (iv) model estimation; (v) evaluation
      of model performance; (vi) internal validation; and (vii) model presentation. The
      validity of a prediction model is ideally assessed in fully independent data,
      where we propose four key measures to evaluate model performance: calibration-in
      the-large, or the model intercept (A); calibration slope (B); discrimination,
      with a concordance statistic (C); and clinical usefulness, with decision-curve
      analysis (D). As an application, we develop and validate prediction models for 30
      day mortality in patients with an acute myocardial infarction. This illustrates
      the usefulness of the proposed framework to strengthen the methodological rigour
      and quality for prediction models in cardiovascular research. 

PMID- 24898553
TI  - Heart failure with preserved ejection fraction: a forest of a variety of trees.

PMID- 24898552
TI  - Catheter-based renal denervation for treatment of patients with treatment
      resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized
      clinical trial.
AB  - AIM: The aim of this study was to determine long-term results of renal artery
      denervation for treatment of treatment-resistant hypertension in the SYMPLICITY
      HTN-2 study. METHODS: SYMPLICITY HTN-2 randomized 106 subjects with treatment
      resistant hypertension to renal denervation or medical therapy alone. At 6
      months, 37 control subjects crossed over to renal denervation. Office blood
      pressure measurements, antihypertensive medication use, and safety events were
      followed every 6 months through 3 years. RESULTS: Follow-up was available at 36
      months in 40 of 52 subjects in the initial renal denervation group and at 30
      months in 30 of 37 subjects who crossed over and received renal denervation at 6
      months. Baseline blood pressure was 184 +/- 19/99 +/- 16 mmHg in all treated
      subjects. At 30-month post-procedure, systolic blood pressure decreased 34 mmHg
      (95% CI: -40, -27, P < 0.01) and diastolic blood pressure decreased 13 mmHg (95%
      CI: -16, -10, P < 0.01). The systolic and diastolic blood pressure reduction at
      36 months for the initial renal denervation group was -33 mmHg (95% CI: -40, -25,
      P < 0.01) and -14 mmHg (95% CI: -17, -10, P < 0.01), respectively. Procedural
      complications included one haematoma, and one renal artery dissection before
      energy delivery that was treated successfully. Later complications included two
      cases of acute renal failure, which fully resolved, 15 hypertensive events
      requiring hospitalization, and three deaths. CONCLUSION: Renal denervation
      resulted in sustained lowering of blood pressure at 3 years in a selected
      population of subjects with severe, treatment-resistant hypertension without
      serious safety concerns. CLINICAL TRIAL REGISTRATION: NCT00888433.

PMID- 24898554
TI  - Research progress in signalling pathway in diabetic nephropathy.
AB  - Diabetic nephropathy, a lethal diabetic complication, is a leading cause of end
      stage renal disease, which is pathologically characterized by thickened tubular
      basal and glomerular membranes, accumulated extracellular matrix, and progressive
      mesangial hypertrophy. Growing evidence indicates that diabetic nephropathy is
      induced by multiple conditions, such as glucose metabolism disorder, oxidative
      stress, numerous inflammatory factors and cytokines, and haemodynamic changes
      that lead to the occurrence and development of diabetic nephropathy based on
      genetic susceptibility. A variety of abnormalities in the signalling pathway may
      interact to produce these pathologic processes. Research has aimed to highlight
      the signalling pathway mechanisms that lead to diabetic nephropathy so that
      preventative strategies and effective therapies might be developed. In this
      review, important pathways that appear to be involved in driving these processes
      are discussed.

PMID- 24898555
TI  - An engineering-based approach for design and fabrication of a customized nasal
      prosthesis.
AB  - BACKGROUND AND AIM: Facial defects (from neoplasms, trauma, etc.) can be
      functionally and emotionally devastating. A non-invasive treatment for these
      defects is the application of external prostheses. Conventionally, these
      prostheses are fabricated by an anaplastologist through a manual procedure, which
      is an expensive and time-consuming approach. Current advances in computational
      and engineering tools report an improvement in design and manufacturing of
      silicone prostheses. This demand motivated this study that aims to develop a
      methodology for fabricating customized nasal prostheses. TECHNIQUE: In this
      study, an 80-year-old woman with a total defect of the nose is considered as case
      study. The proposed methodology entails six tasks: (a) data acquisition, (b)
      three-dimensional reconstruction, (c) prosthesis design, (d) moulds fabrication,
      (e) prosthesis manufacturing and (f) final fittings. DISCUSSION: The presented
      approach showed encouraging outcomes since it saves time, reduces costs and
      allows the achievement of prosthesis with the minimum contact and discomfort to
      the patient, disclosing excellent aesthetic and functional results. CLINICAL
      RELEVANCE: Custom-made nasal prostheses with minimum contact and discomfort for
      the patient can be achieved using an engineering approach based on digital
      technologies and additive manufacturing that is cost-effective and less time
      consuming than the manual procedure.

PMID- 24898556
TI  - Inhibition of soleus Hoffmann reflex by ankle-foot orthosis application in
      healthy volunteers.
AB  - BACKGROUND: An ankle-foot orthosis is suggested to actively assist dorsiflexion
      of the foot by induction of a positive proprioceptive impact to ankle dorsiflexor
      muscles. However, an objective proof is missing. OBJECTIVES: To assess the
      proprioceptive impact of an ankle-foot orthosis application by Hoffmann reflex
      recordings of the soleus muscle under static conditions. It was hypothesized that
      the use of an ankle-foot orthosis facilitated dorsiflexor motor function and thus
      a decreased the soleus Hoffmann reflex. STUDY DESIGN: Experimental study in
      healthy volunteers, pre-post test design. METHODS: In all, 20 healthy volunteers
      were enrolled in order to assess the proprioceptive impact of orthosis
      application. The Hoffmann reflex was recorded before, during, and after orthosis
      application. RESULTS: Under orthosis application, the Hoffmann reflex
      significantly decreased as compared to before (p < 0.05) and after application (p
      < 0.05). CONCLUSIONS: Findings indicate an inhibition of plantarflexors probably
      induced by facilitation of ankle dorsiflexors under static conditions. At first
      glance, it seems that foot orthoses primarily have a stabilizing effect on ankle
      joints in terms of simple mechanical bandages. However, the present results
      suggest an additional active impact on proprioceptive control. CLINICAL
      RELEVANCE: The putative neuromodulatory effect on motor control may support the
      application of such ankle-foot orthoses in, for example, drop foot. Furthermore,
      the objective assessment of a neurophysiological mode of action of orthoses by
      Hoffmann reflex recordings might be an appropriate primary outcome parameter in
      clinical trials.

PMID- 24898557
TI  - Dentist-specific effects on the longevity of dental restorations.
AB  - BACKGROUND: Numerous studies have been carried out on the longevity of
      restorations. The focus in these studies has been to explain differences in
      longevity according to characteristics of the patient and type of restoration. No
      attempts have been made to estimate dentist-specific effects, that is, how much
      of the variation in longevity can be explained by dentist variation compared with
      patient variation. If dentist-specific variation is large, this may indicate a
      need to reassess the way dentists are taught restorative dentistry, or it may
      indicate a need for further education of qualified dentists. OBJECTIVES: To
      estimate dentist-specific variation in the longevity of restorations in the first
      permanent molars for children aged 6-18 years in Norway. METHODS: The data set
      encompassed all children born in 1993 who received one or more restorations in
      their first permanent molars. This encompassed 72 573 restorations for 64,728
      children who were treated by 2473 public dental officers. The data were analysed
      using two multilevel models--mixed-effects logistic regression and mixed-effects
      linear regression. RESULTS: The dentist-specific variation was low. The
      intraclass correlation coefficient varied from 0.03 to 0.09 in different
      specifications. CONCLUSIONS: Public dental officers in Norway show a high degree
      of homogeneity with regard to longevity of restorations. Further improvements in
      the longevity of restorations can most likely be achieved by preventing secondary
      caries and by improving the physical properties of materials.

PMID- 24898558
TI  - Recharging or Retiring Older Workers? Uncovering the Age-Based Strategies of
      European Employers.
AB  - PURPOSE OF THE STUDY: We offer an empirically based taxonomy of the human
      resource policies of European employers in relation to older workers. In
      particular, 3 age-based strategies are discussed and analyzed in a simultaneous
      fashion: a focus on exit through retirement, workplace accommodation measures,
      and employee development measures. DESIGN AND METHODS: A sample of 3,638
      organizations in 6 European countries (Denmark, Germany, Italy, The Netherlands,
      Poland, and Sweden) is analyzed to discover which of the 7 antecedents
      investigated herein are associated with the implementation of these human
      resource strategies. The key predictors are the proportion of older workers (aged
      50 or older), organization size, seniority-based compensation, labor union
      involvement, training requirement, recruitment problems, and knowledge intensity.
      Structural equation modeling is used to assess whether these predictors are
      associated with the 3 latent factors. RESULTS: The 7 key predictors of the 3
      strategies show that these strategies are used simultaneously, but that the
      employers clearly use exit policies more intensively than they use development
      measures. Organizations thus use a dual approach to managing the employment of
      older workers. They may sort older workers either upwards (e.g., by encouraging
      career development and training) or outwards (by promoting early retirement). The
      same division can be detected when examining the effects of labor union
      involvement and seniority-based wages. When recruitment problems are encountered,
      more effort is directed toward accommodation and investment. IMPLICATIONS:
      Despite the warnings of policymakers about the possible consequences of an aging
      population, European employers are not yet formulating strategies that promote
      active aging, often still opting for the easy way out, via exit strategies.

PMID- 24898559
TI  - Effect of dutasteride 0.5 mg/d in men with androgenetic alopecia recalcitrant to
      finasteride.
AB  - BACKGROUND: Finasteride at a dose of 1 mg/d has been reported to show no
      significant improvement in 30-50% of patients with androgenetic alopecia (AGA).
      Dutasteride, a dual inhibitor of both type I and type II 5 alpha-reductase,
      inhibits the conversion of testosterone to dihydrotestosterone, which is the key
      contributor of AGA. MATERIALS AND METHODS: Our aim is to evaluate clinical
      efficacy and tolerability of dutasteride in men with AGA who do not show clinical
      improvement to the conventional finasteride treatment. A total of 35 Korean men
      with AGA who had not shown significant clinical improvement when treated with
      finasteride 1 mg/d for at least six months received dutasteride at a dose of 0.5
      mg/d for six months. Efficacy was evaluated by global photograph assessment and
      phototrichogram. Safety assessment was performed through physical examination and
      adverse event report. RESULTS: Of the 31 patients who completed the treatment, 24
      patients (77.4%) were improved by the global photography (17 were slightly, six
      moderately, and one markedly improved) compared with the post-finasteride
      treatment. There was no significant change in seven patients (22.6%), and
      aggravation was not reported. Hair density and thickness significantly increased
      by 10.3% (87 +/- 12-96 +/- 12/cm(2)) and 18.9% (0.053 +/- 0.012-0.063 +/- 0.011
      mm), respectively, in phototrichogram assessment. Side effects included transient
      sexual dysfunction in six patients (17.1%). CONCLUSIONS: Dutasteride is
      suggestive to be an alternative treatment option to patients with AGA who do not
      clinically respond to finasteride in six months.

PMID- 24898560
TI  - Multiple clear cell acanthoma associated with multiple Bowen's disease.

PMID- 24898562
TI  - Preoperative differentiation of thyroid adenomas and thyroid carcinomas using
      high resolution contrast-enhanced ultrasound (CEUS).
AB  - BACKGROUND: To evaluate the impact of high-resolution contrast-enhanced
      ultrasound (CEUS) in combination with Color Coded and Power Doppler Sonography
      (CCDS/PD) in the preoperative differentiation of thyroid adenomas and thyroid
      carcinomas. METHODS: A total of 101 patients (55 female, median age 54 years)
      underwent surgery for thyroid adenoma and thyroid carcinoma. CCDS/PD and CEUS
      were performed in all patients by an experienced examiner using a multifrequency
      linear transducer (6-9 or 6-15 MHz) and were digitally stored. Reading of the
      ultrasound images was performed by two experienced radiologists in consensus. A
      histopathological evaluation was obtained as standard of reference in all
      patients. RESULTS: Altogether, 75 thyroid adenomas and 26 thyroid carcinomas were
      detected. Mean diameter of thyroid adenomas and thyroid carcinomas was 27 mm and
      32 mm, respectively. The differences in microcirculation of thyroid adenomas and
      thyroid carcinomas were statistically highly significant (p <  0.01).
      Representative features for thyroid adenomas were either no wash-out or wash-out
      with persisting edge in late phase, for thyroid carcinomas a complete wash-out in
      late phase. Thus, a calculation of sensitivity, specificity, positive and
      negative predictive value of 81% , 92% , 97% and 63%, respectively, for the
      differentiation of benignity and malignancy was possible. CONCLUSIONS: Dynamic
      evaluation of microcirculation using CEUS and CCDS/PD enables a more reliable
      preoperative discrimination between thyroid adenomas and thyroid carcinomas.

PMID- 24898563
TI  - Separating proteins with activated carbon.
AB  - Activated carbon is applied to separate proteins based on differences in their
      size and effective charge. Three guidelines are suggested for the efficient
      separation of proteins with activated carbon. (1) Activated carbon can be used to
      efficiently remove smaller proteinaceous impurities from larger proteins. (2)
      Smaller proteinaceous impurities are most efficiently removed at a solution pH
      close to the impurity's isoelectric point, where they have a minimal effective
      charge. (3) The most efficient recovery of a small protein from activated carbon
      occurs at a solution pH further away from the protein's isoelectric point, where
      it is strongly charged. Studies measuring the binding capacities of individual
      polymers and proteins were used to develop these three guidelines, and they were
      then applied to the separation of several different protein mixtures. The ability
      of activated carbon to separate proteins was demonstrated to be broadly
      applicable with three different types of activated carbon by both static
      treatment and by flowing through a packed column of activated carbon. 

PMID- 24898564
TI  - Lateralized enhancement of auditory cortex activity and increased sensitivity to
      self-generated sounds.
AB  - Performing actions with auditory consequences modulates the response in auditory
      cortex to otherwise identical stimuli passively heard. Such modulation has been
      suggested to occur through a corollary discharge sent from the motor cortex
      during voluntary actions. However, the relationship between the effector used to
      generate the sound, type of modulation and changes in perceptual sensitivity are
      unclear. Here we use functional magnetic resonance imaging on healthy subjects
      and demonstrate bilateral enhancement in the auditory cortex to self-generated
      versus externally generated sounds. Furthermore, we find that this enhancement is
      stronger when the sound-producing hand is contralateral to the auditory cortex.
      At the behavioural level, binaural hearing thresholds are lower for self
      generated sounds and monaural thresholds are lower for sounds triggered by the
      hand ipsilateral to the stimulated ear. Together with functional connectivity
      analysis, our results suggest that a corollary discharge sent from active motor
      cortex enhances activity in the auditory cortex and increases perceptual
      sensitivity in a lateralized manner. 

PMID- 24898561
TI  - Increased erythrocyte adhesion to VCAM-1 during pulsatile flow: Application of a
      microfluidic flow adhesion bioassay.
AB  - Sickle cell disease (SCD) is characterized by microvascular occlusion mediated by
      adhesive interactions of sickle erythrocytes (SSRBCs) to the endothelium. Most in
      vitro flow adhesion assays measure SSRBC adhesion during continuous flow,
      although in vivo SSRBC adhesive interactions occur during pulsatile flow. Using a
      well-plate microfluidic flow adhesion system, we demonstrate that isolated SSRBCs
      adhere to vascular cell adhesion molecule (VCAM-1) at greater levels during
      pulsatile versus continuous flow. A significant increase in adhesive interactions
      was observed between all pulse frequencies 1 Hz to 2 Hz (60-120 beats/min) when
      compared to non-pulsatile flow. Adhesion of isolated SSRBCs and whole blood
      during pulsatile flow was unaffected by protein kinase A (PKA) inhibition, and
      exposure of SSRBCs to pulsatile flow did not affect the intrinsic adhesive
      properties of SSRBCs. The cell type responsible for increased adhesion of whole
      blood varied from patient to patient. We conclude that low flow periods of the
      pulse cycle allow more adhesive interactions between sickle erythrocytes and VCAM
      1, and sickle erythrocyte adhesion in the context of whole blood may better
      reflect physiologic cellular interactions. The microfluidic flow adhesion
      bioassay used in this study may have applications for clinical assessment of
      sickle erythrocyte adhesion during pulsatile flow. 

PMID- 24898565
TI  - The riddle of the springs of Dilmun--does the Gilgamesh epic tell the truth?

PMID- 24898567
TI  - Biotin-decorated silica coated PbS nanocrystals emitting in the second biological
      near infrared window for bioimaging.
AB  - Nanoparticles (NPs) emitting in the second biological near infrared (NIR) window
      of the electromagnetic spectrum have been successfully synthesized by growing a
      silica shell on the hydrophobic surface of OLEA/TOP PbS nanocrystals (NCs), by
      means of a reverse microemulsion approach, and subsequently decorated with biotin
      molecules. The fabrication of very uniform and monodisperse NPs, formed of SiO2
      shell coated single core PbS NCs, has been demonstrated by means of a set of
      complementary optical and structural techniques (Vis-NIR absorption and
      photoluminescence spectroscopy, transmission electron microscopy) that have
      highlighted how experimental parameters, such as PbS NC and silica precursor
      concentration, are crucial to direct the morphology and optical properties of
      silica coated PbS NPs. Subsequently, the silica surface of the core-shell NPs has
      been grafted with amino groups, in order to achieve covalent binding of biotin to
      NIR emitting silica coated NPs. Finally the successful reaction with a green
      fluorescent labelled streptavidin has verified the molecular recognition response
      of the biotin molecules decorating the PbS@SiO2 NP surface. Dynamic light
      scattering (DLS) and zeta-potential techniques have been used to monitor the
      hydrodynamic diameter and colloidal stability of both PbS@SiO2 and biotin
      decorated NPs, showing their high colloidal stability in physiological media, as
      needed for biomedical applications. Remarkably the obtained biotinylated PbS@SiO2
      NPs have been found to retain emission properties in the 'second optical window'
      of the NIR region of the electromagnetic spectrum, thus representing attractive
      receptor-targeted NIR fluorescent probes for in vivo tumour imaging.

PMID- 24898566
TI  - Human cellular differences in cAMP--CREB signaling correlate with light-dependent
      melatonin suppression and bipolar disorder.
AB  - Various lines of evidence suggest a mechanistic role for altered cAMP-CREB (cAMP
      response element - binding protein) signaling in depressive and affective
      disorders. However, the establishment and validation of human inter-individual
      differences in this and other major signaling pathways has proven difficult.
      Here, we describe a novel lentiviral methodology to investigate signaling
      variation over long periods of time directly in human primary fibroblasts. On a
      cellular level, this method showed surprisingly large inter-individual
      differences in three major signaling pathways in human subjects that nevertheless
      correlated with cellular measures of genome-wide transcription and drug toxicity.
      We next validated this method by establishing a likely role for cAMP-mediated
      signaling in a human neuroendocrine response to light - the light-dependent
      suppression of the circadian hormone melatonin - that shows wide inter-individual
      differences of unknown origin in vivo. Finally, we show an overall greater
      magnitude of cellular CREB signaling in individuals with bipolar disorder,
      suggesting a possible role for this signaling pathway in susceptibility to mental
      disease. Overall, our results suggest that genetic differences in major signaling
      pathways can be reliably detected with sensitive viral-based reporter profiling,
      and that these differences can be conserved across tissues and be predictive of
      physiology and disease susceptibility.

PMID- 24898568
TI  - Transfusion-related acute lung injury after transfusion of pooled immune
      globulin: a case report.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is a severe transfusion
      reaction that manifests as acute respiratory compromise within 6 hours of the
      infusion of blood products. Intravenous immune globulin (IVIG) is prepared from
      large pools of human plasma and is commonly administered in the outpatient
      setting for the treatment of a wide range of diseases. As a plasma-derived blood
      product, IVIG may also cause TRALI, although reports of this are exceedingly
      rare. CASE REPORT: A 77-year-old female with common variable immune deficiency
      had been receiving IVIG since 1996 for infection prophylaxis. During a scheduled
      infusion, the patient developed hypertension and dyspnea, requiring increasing
      oxygen supplementation and subsequent intubation. Radiographic studies
      demonstrated the bilateral chest infiltrates, with no evidence of infection or
      circulatory overload. The patient was extubated after 24 hours and discharged
      several days later. The patient had not previously received this lot of IVIG and
      has since received further transfusions with different lot numbers of the same
      product without incident. CONCLUSION: This case report documents a case of TRALI
      after IVIG transfusion. While a very rare cause, this case furthers evidence that
      TRALI can occur after IVIG transfusion.

PMID- 24898569
TI  - High density GaN/AlN quantum dots for deep UV LED with high quantum efficiency
      and temperature stability.
AB  - High internal efficiency and high temperature stability ultraviolet (UV) light
      emitting diodes (LEDs) at 308 nm were achieved using high density (2.5 * 10(9)
      cm(-2)) GaN/AlN quantum dots (QDs) grown by MOVPE. Photoluminescence shows the
      characteristic behaviors of QDs: nearly constant linewidth and emission energy,
      and linear dependence of the intensity with varying excitation power. More
      significantly, the radiative recombination was found to dominant from 15 to 300
      K, with a high internal quantum efficiency of 62% even at room temperature. 

PMID- 24898570
TI  - L-arginine and tetrahydrobiopterin, but not sodium nitrite partially restored
      erectile dysfunction in aged rats.
AB  - Aging is associated with erectile dysfunction (ED), in which nitric oxide
      synthase (NOS) activity and NO bioavailability are reduced due to deficiencies of
      NOS cofactor (tetrahydrobiopterin, BH(4)) and substrate (L-arginine). We
      determined whether the prolonged treatment with sodium nitrite (NaNO(2)) as a
      storage form of NO ameliorates ED in aged rats. Male Sprague-Dawley rats were
      divided: younger, aged and NaNO(2)-treated (20 mg/kg per day) aged groups. The
      erectile (intracavernosal pressure [ICP]/mean arterial pressure [MAP]) and corpus
      cavernous (CC) responses were evaluated after 12 weeks. The ICP/MAP in aged rats
      was lower than in young controls, which was not improved by the NaNO(2)
      treatment. Immunohistochemical (IHC) staining for endothelial NOS and collagen
      deposition was performed. We assayed NO indirectly by measuring the level of its
      stable end products, nitrite/nitrate, using the Griess reagent. The relaxations
      to ACh and EFS in the aged group were considerably less than in the younger
      group, which were normalized by acute incubations of l-arginine or BH(4) of aged
      CC. In conclusion, NaNO(2) treatment did not restore erectile response while
      nitrate levels were enhanced in aged penis. The cofactor or substrate
      administrations, but not chronic exogenous modulation of NO system may be
      beneficial in aged men with ED.

PMID- 24898572
TI  - Editorial.

PMID- 24898571
TI  - Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional
      study in a tertiary emergency department.
AB  - BACKGROUND: To date, the use of proton pump inhibitors (PPIs) has been associated
      with a low risk of hypomagnesaemia and associated adverse outcomes. We
      hypothesised that a better risk estimate could be derived from a large cohort of
      outpatients admitted to a tertiary emergency department (ED). METHODS: A cross
      sectional study was performed in 5118 patients who had measurements of serum
      magnesium taken on admission to a large tertiary care ED between January 2009 and
      December 2010. Hypomagnesaemia was defined as a serum magnesium concentration <
      0.75 mmol/l. Demographical data, serum electrolyte values, data on medication,
      comorbidities and outcome with regard to length of hospital stay and mortality
      were analysed. RESULTS: Serum magnesium was normally distributed where upon 1246
      patients (24%) were hypomagnesaemic. These patients had a higher prevalence of
      out-of-hospital PPI use and diuretic use when compared with patients with
      magnesium levels > 0.75 mmol/l (both p < 0.0001). In multivariable regression
      analyses adjusted for PPIs, diuretics, renal function and the Charlson
      comorbidity index score, the association between use of PPIs and risk for
      hypomagnesaemia remained significant (OR = 2.1; 95% CI: 1.54-2.85). While
      mortality was not directly related to low magnesium levels (p = 0.67), the length
      of hospitalisation was prolonged in these patients even after adjustment for
      underlying comorbid conditions (p < 0.0001). CONCLUSION: Use of PPIs predisposes
      patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of
      the underlying morbidity, posing a critical concern.

PMID- 24898573
TI  - Lichen planopilaris following whole brain irradiation.

PMID- 24898575
TI  - Comparison of clinical characteristics of chronic cough due to non-acid and acid
      gastroesophageal reflux.
AB  - BACKGROUND AND OBJECTIVE: Little is known about non-acid gastroesophageal reflux
      induced chronic cough (GERC). The purpose of the study is to explore the clinical
      characteristics of non-acid GERC. METHODS: Clinical symptoms, cough symptom
      score, capsaicin cough sensitivity, gastroesophageal reflux diagnostic
      questionnaire (GerdQ) score, findings of multichannel intraluminal impedance-pH
      monitoring (MII-pH) and response to pharmacological anti-reflux therapy were
      retrospectively reviewed in 38 patients with non-acid GERC and compared with
      those of 49 patients with acid GERC. RESULTS: Non-acid GERC had the similar cough
      character, cough symptom score, and capsaicin cough sensitivity to acid GERC.
      However, non-acid GERC had less frequent regurgitation (15.8% vs 57.1%, chi(2)  =
      13.346, P = 0.000) and heartburn (7.9% vs 32.7%, chi(2)  = 7.686, P  = 0.006),
      and lower GerdQ score (7.4 +/- 1.4 vs 10.6 +/- 2.1, t = -6.700, P = 0.003) than
      acid GERC. Moreover, MII-pH revealed more weakly acidic reflux episodes, gas
      reflux episodes and a higher symptom association probability (SAP) for non-acid
      reflux but lower DeMeester score, acidic reflux episodes and SAP for acid reflux
      in non-acid GERC than in acid GERC. Non-acid GERC usually responded to the
      standard anti-reflux therapy but with delayed cough resolution or attenuation
      when compared with acid GERC. Fewer patients with non-acid GERC needed an
      augmented acid suppressive therapy or treatment with baclofen. CONCLUSIONS: There
      are some differences in the clinical manifestations between non-acid and acid
      GERC, but MII-pH is essential to diagnose non-acid GERC.

PMID- 24898574
TI  - Changes in motor cortex excitability associated with temporal repetitive
      transcranial magnetic stimulation in tinnitus: hints for cross-modal plasticity?
AB  - BACKGROUND: Motor cortex excitability was found to be changed after repetitive
      transcranial magnetic stimulation (rTMS) of the temporal cortex highlighting the
      occurrence of cross-modal plasticity in non-invasive brain stimulation. Here, we
      investigated the effects of temporal low-frequency rTMS on motor cortex
      plasticity in a large sample of tinnitus patients. In 116 patients with chronic
      tinnitus different parameters of cortical excitability were assessed before and
      after ten rTMS treatment sessions. Patients received one of three different
      protocols all including 1 Hz rTMS over the left temporal cortex. Treatment
      response was defined as improvement by at least five points in the tinnitus
      questionnaire (TQ). Variables of interest were resting motor threshold (RMT),
      short-interval intra-cortical inhibition (SICI), intracortical facilitation
      (ICF), and cortical silent period (CSP). RESULTS: After rTMS treatment RMT was
      decreased by about 1% of stimulator output near-significantly in the whole group
      of patients. SICI was associated with significant changes with respect to
      treatment response. The group of treatment responders showed a decrease of SICI
      over the course of treatment, the group of non-responders the reverse pattern.
      CONCLUSIONS: Minor RMT changes during rTMS treatment do not necessarily suggest
      the need for systematic re-examination of the RMT for safety and efficacy issues.
      Treatment response to rTMS was shown to be related to changes in SICI that might
      reflect modulation of GABAergic mechanisms directly or indirectly related to rTMS
      treatment effects.

PMID- 24898576
TI  - Anti-inflammatory effects of Perilla frutescens leaf extract on
      lipopolysaccharide-stimulated RAW264.7 cells.
AB  - Perilla leaves are widely used in Chinese herbal medicine and in Japanese herbal
      agents used to treat respiratory diseases. This study aimed to investigate the
      anti-inflammatory effects and the underlying mechanisms of Perilla frutescens
      leaf extract (PLE). Murine macrophage RAW264.7 cells were used as a model. Cell
      viability and morphological changes were studied by the MTT assay and microscopy.
      mRNA expression of pro-inflammatory mediators was assessed by both semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) and
      quantitative (q) RT-PCR. Nitric oxide (NO) and prostaglandin E2 (PGE2) production
      were analyzed by the Griess test and sandwich enzyme-linked immunosorbent assay
      (ELISA), respectively. The activation of kinase cascades was studied by
      immunoblotting. Our findings showed that PLE slightly affects cell viability, but
      alleviates LPS-induced activation of RAW264.7 cells. Furthermore, PLE
      significantly reduced the LPS-induced mRNA expression of the interleukin (IL)-6,
      IL-8, tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and
      inducible nitric oxide synthase (iNOS), genes in a dose-dependent manner. In
      addition, PLE reduced NO production and PGE2 secretion induced by LPS. PLE also
      inhibited activation of mitogen-activated protein kinases (MAPKs), increased the
      cytosolic IkappaBalpha level, and reduced the level of nuclear factor (NF)
      kappaB. Taken together, these findings indicate that PLE significantly decreases
      the mRNA expression and protein production of pro-inflammatory mediators, via the
      inhibition of extracellular-signal-regulated kinase (ERK)1/2, c-Jun N-terminal
      kinase (JNK), p38, as well as NF-kappaB signaling in RAW264.7 cells stimulated
      with LPS. 

PMID- 24898577
TI  - Immunotherapy of type-1 allergies with virus-like particles and CpG-motifs.
AB  - Immunotherapy of type-I-allergies is regarded as the most efficient treatment
      option besides allergen avoidance. Different forms of allergen preparations are
      used as well as different routes of application. Virus-like particles represent a
      potent vaccine platform with proven immunogenicity and clinical efficacy. The
      addition of toll-like receptor ligands and/or depot-forming adjuvants further
      enhances immune cell activation. This article will focus on the function of virus
      like particles loaded with DNA rich in CpG-motifs and discuss clinical experience
      in treatment of allergic rhinitis. Evidence will be presented that clinically
      effective treatment can be obtained even in the absence of allergens. Results
      encourage further investigation of virus-like particles and CpG-motifs in
      immunotherapy, either as a stand alone product, or as adjuvants for allergen
      specific immunotherapy. 

PMID- 24898578
TI  - Attitudinal factors protective against youth smoking: an integrative review.
AB  - PURPOSE: This review examines recent literature with the purpose of uncovering
      associations between attitudinal factors and smoking among youth populations.
      ORGANIZING CONSTRUCT AND METHODS: Researchers conducted an integrative review of
      the literature in late 2012 and early 2013. As inclusion criteria, potential
      articles were measured against the following statement: "There is valid evidence
      of (an) attitudinal factor(s) potentially associated with smoking among youth."
      FINDINGS: Researchers employed the salutogenic model as a theoretical framework
      to analyze search results. The narrative synthesis indicates that primary
      attitudinal factors protective against smoking among youth include the following:
      (a) a perception that there is little benefit to smoking, (b) a belief that
      smoking is likely harmful and addictive in the short term, and (c) a denial that
      smoking provides stress abatement, makes one look cool or more grown-up, or is
      common and accepted. Moreover, research signals that youth who smoke often
      demonstrate essentially the opposite beliefs and attitudes. CONCLUSIONS: Findings
      suggest attitudinal factors play a role in protection against youth smoking.
      Those youth who assign realistic values to smoking risks and benefits are more
      equipped to engage in the health-protective behavior of not smoking. Youth,
      adolescents, and young adults appear vulnerable to inappropriate designation of
      risk and benefit values of smoking. Theoretical interpretation suggests that
      bolstering attitudinal factors during youth might counteract immature risk
      assessment. These findings justify further research related to protective
      mechanisms against youth smoking and youth-based smoking prevention
      interventions. CLINICAL RELEVANCE: The establishment of associations between
      attitudinal factors and protection against smoking can help determine
      interventions effective in reducing smoking among youth.

PMID- 24898579
TI  - Early postoperative treatment of thyroidectomy scars using botulinum toxin: a
      split-scar, double-blind randomized controlled trial.
AB  - Operational scars, especially those located on the exposed parts of the body, can
      be distressing. Despite high demand for an early intervention to minimize
      surgical scars, there is yet no universal consensus on optimal treatment. A split
      scar, double-blind randomized controlled trial was held to assess the safety and
      efficacy of early postoperative botulinum toxin type A (BTA) injection in
      surgical scars. A single session of treatment was performed where BTA was
      allocated to one half of the scar and 0.9% saline to the control half. Scars were
      assessed using the modified Stony Brook Scar Evaluation Scale (SBSES) with
      standardized photographs. Fifteen patients completed the study, and their data
      were analyzed. At 6 months' follow-up, a significant improvement in SBSES score
      was noted for the BTA-treated halves of the scars (p < 0.001), with minimal
      change on the saline-treated side (p = 0.785). The mean calculated difference in
      SBSES scores (final/initial) between the BTA-treated side and the saline-treated
      side was also significant (p < 0.001). Early postoperative BTA injection was safe
      and effective in modulating thyroidectomy scars and may be a promising option for
      scar prevention. 

PMID- 24898580
TI  - ABO-incompatible heart transplants.
AB  - A month-old baby girl with blood type O positive received a donor heart organ
      from a donor with blood type B. This was the first institutional ABO-incompatible
      heart transplant. Infants listed for transplantation may be considered for an ABO
      incompatible heart transplant based on their antibody levels and age. The United
      Network of Organ Sharing (UNOS) protocol is infants under 24 months with titers
      less than or equal to 1:4.(1) This recipient's anti-A and anti-B antibodies were
      monitored with titer assays to determine their levels; antibody levels less than
      1:4 are acceptable pre-transplant in order to proceed with donor and transplant
      arrangements.1 Immediately prior to initiating cardiopulmonary bypass (CPB), a
      complete whole body exchange transfusion of at least two-times the patient's
      circulating blood volume was performed with packed red blood cells (pRBC), fresh
      frozen plasma (FFP) and 25% albumin. Titer assays were sent two minutes after
      initiation of full CPB and then hourly until the cross-clamp was removed.
      Institutionally, reperfusion of the donor heart is not restored until the
      antibody level from the titer assay is known and reported as less than 1:4;
      failing to achieve an immulogically tolerant recipient will provide conditions
      for hyperacute rejection. The blood collected during the transfusion exchange was
      immediately processed through a cell saver so the pRBC's could be re-infused to
      the patient during CPB, as necessary. The remainder of the transplant was
      performed in the same fashion as an ABO-compatible heart transplant. The patient
      has shown no signs of rejection following transplantation.

PMID- 24898581
TI  - Inhibition of Wnt/beta-catenin signaling promotes epithelial differentiation of
      mesenchymal stem cells and repairs bleomycin-induced lung injury.
AB  - Idiopathic pulmonary fibrosis is a progressive lung disorder of unknown etiology.
      Previous studies have shown that aberrant activation of the Wnt/beta-catenin
      signaling cascade occurs in lungs of patients with idiopathic pulmonary fibrosis.
      Given the important roles of the Wnt/beta-catenin signaling pathway in the
      development of pulmonary fibrosis, we targeted this pathway for the intervention
      of pulmonary fibrosis with XAV939, a small molecule that specifically inhibits
      Tankyrase 1/2, eventually leading to the degradation of beta-catenin and
      suppression of the Wnt/beta-catenin signaling pathway. Our results demonstrated
      that XAV939 significantly inhibited the activation of Wnt/beta-catenin signaling
      and attenuated bleomycin-induced lung fibrosis in mice, and thus improved the
      survival of mice with lung injury. Interestingly, previous investigations have
      confirmed that endogenous and exogenous mesenchymal stem cells could be recruited
      to the injured lung, although the exact effects of these cells are debatable. To
      determine the effect of Wnt/beta-catenin signaling in the epithelial
      differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs), we
      established a coculture system that contains BM-MSCs and alveolar type II
      epithelial cells. The in vitro experiments demonstrated that XAV939 could promote
      the differentiation of BM-MSCs into an epithelium-like phenotype in the coculture
      system. We also found that XAV939 could inhibit the proliferation and
      myofibroblast differentiation of NIH/3T3 fibroblasts. This work supports that
      inhibition of the Wnt/beta-catenin signaling pathway may be exploited for the
      treatment of idiopathic pulmonary fibrosis for which effective treatment
      strategies are still lacking.

PMID- 24898582
TI  - A two-pronged weapon in the fight against fibrosis. Focus on "Inhibition of
      Wnt/beta-catenin signaling promotes epithelial differentiation of mesenchymal
      stem cells and repairs bleomycin-induced lung injury".

PMID- 24898583
TI  - Role of anion exchangers in Cl- and HCO3- secretion by the human airway
      epithelial cell line Calu-3.
AB  - Despite the importance of airway surface liquid pH in the lung's defenses against
      infection, the mechanism of airway HCO3- secretion remains unclear. Our aim was
      to assess the contribution of apical and basolateral Cl-/HCO3- exchangers to Cl-
      and HCO3- transport in the Calu-3 cell line, derived from human airway submucosal
      glands. Changes in intracellular pH (pHi) were measured following substitution of
      Cl- with gluconate. Apical Cl- substitution led to an alkalinization in forskolin
      stimulated cells, indicative of Cl-/HCO3- exchange. This was unaffected by the
      anion exchange inhibitor DIDS but inhibited by the CFTR blocker CFTRinh-172,
      suggesting that the HCO3- influx might occur via CFTR, rather than a solute
      carrier family 26 (SLC26) exchanger, as recently proposed. The anion selectivity
      of the recovery process more closely resembled that of CFTR than an SLC26
      exchanger, and quantitative RT-PCR showed only low levels of SLC26 exchanger
      transcripts relative to CFTR and anion exchanger 2 (AE2). For pHi to rise to
      observed values (~7.8) through HCO3- entry via CFTR, the apical membrane
      potential must reverse to at least +20 mV following Cl- substitution; this was
      confirmed by perforated-patch recordings. Substitution of basolateral Cl- evoked
      a DIDS-sensitive alkalinization, attributed to Cl-/HCO3- exchange via AE2. This
      appeared to be abolished in forskolin-stimulated cells but was unmasked by
      blocking apical efflux of HCO3- via CFTR. We conclude that Calu-3 cells secrete
      HCO3- predominantly via CFTR, and, contrary to previous reports, the basolateral
      anion exchanger AE2 remains active during stimulation, providing an important
      pathway for basolateral Cl- uptake.

PMID- 24898584
TI  - Cystic fibrosis transmembrane conductance regulator dysfunction in VIP knockout
      mice.
AB  - Vasoactive intestinal peptide (VIP), a neuropeptide, controls multiple functions
      in exocrine tissues, including inflammation, and relaxation of airway and
      vascular smooth muscles, and regulates CFTR-dependent secretion, which
      contributes to mucus hydration and local innate defense of the lung. We had
      previously reported that VIP stimulates the VPAC1 receptor, PKCepsilon signaling
      cascade, and increases CFTR stability and function at the apical membrane of
      airway epithelial cells by reducing its internalization rate. Moreover, prolonged
      VIP stimulation corrects the molecular defects associated with F508del, the most
      common CFTR mutation responsible for the genetic disease cystic fibrosis. In the
      present study, we have examined the impact of the absence of VIP on CFTR
      maturation, cellular localization, and function in vivo using VIP knockout mice.
      We have conducted pathological assessments and detected signs of lung and
      intestinal disease. Immunodetection methods have shown that the absence of VIP
      results in CFTR intracellular retention despite normal expression and maturation
      levels. A subsequent loss of CFTR-dependent chloride current was measured in
      functional assays with Ussing chamber analysis of the small intestine ex vivo,
      creating a cystic fibrosis-like condition. Interestingly, intraperitoneal
      administration of VIP corrected tissue abnormalities, close to the wild-type
      phenotype, as well as associated defects in the vital CFTR protein. The results
      show in vivo a primary role for VIP chronic exposure in CFTR membrane stability
      and function and confirm in vitro data. 

PMID- 24898585
TI  - A dominantly negative mutation in cardiac troponin I at the interface with
      troponin T causes early remodeling in ventricular cardiomyocytes.
AB  - We previously reported a point mutation substituting Cys for Arg(111) in the
      highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI)
      in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825-13832, 2004).
      This dominantly negative TnI-TnT interface mutation decreases the binding
      affinity of cTnI for TnT, impairs diastolic function, and blunts the beta
      adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806-27816,
      2010). Here we further investigate cellular phenotypes of transgenic mouse
      cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies
      were performed on single adult cardiomyocytes after recovery in short-term
      culture from isolation stress. The amplitude of contraction and the velocities of
      shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild
      type controls. The intracellular Ca(2+) transient was slower in cTnI-K118C
      cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a
      weaker beta-adrenergic response. The resting length of cTnI-K118C cardiomyocytes
      was significantly greater than that of age-matched wild-type cells, with no
      difference in cell width. The resting sarcomere was not longer, but slightly
      shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating
      longitudinal addition of sarcomeres. More tri- and quadrinuclei cardiomyocytes
      were found in TnI-K118C than wild-type hearts, suggesting increased nuclear
      divisions. Whole-genome mRNA array and Western blots detected an increased
      expression of leukemia inhibitory factor receptor-beta in the hearts of 2-mo-old
      cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect
      of cTnI-K118C mutation on early remodeling in cardiomyocytes. 

PMID- 24898586
TI  - Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an
      integrative model.
AB  - The uptake of glucose and the nutrient coupled transcellular sodium traffic
      across epithelial cells in the small intestine has been an ongoing topic in
      physiological research for over half a century. Driving the uptake of nutrients
      like glucose, enterocytes must have regulatory mechanisms that respond to the
      considerable changes in the inflow of sodium during absorption. The Na-K-ATPase
      membrane protein plays a major role in this regulation. We propose the hypothesis
      that the amount of active Na-K-ATPase in enterocytes is directly regulated by the
      concentration of intracellular Na(+) and that this regulation together with a
      regulation of basolateral K permeability by intracellular ATP gives the
      enterocyte the ability to maintain ionic Na(+)/K(+) homeostasis. To explore these
      regulatory mechanisms, we present a mathematical model of the sodium coupled
      uptake of glucose in epithelial enterocytes. Our model integrates knowledge about
      individual transporter proteins including apical SGLT1, basolateral Na-K-ATPase,
      and GLUT2, together with diffusion and membrane potentials. The intracellular
      concentrations of glucose, sodium, potassium, and chloride are modeled by
      nonlinear differential equations, and molecular flows are calculated based on
      experimental kinetic data from the literature, including substrate saturation,
      product inhibition, and modulation by membrane potential. Simulation results of
      the model without the addition of regulatory mechanisms fit well with published
      short-term observations, including cell depolarization and increased
      concentration of intracellular glucose and sodium during increased concentration
      of luminal glucose/sodium. Adding regulatory mechanisms for regulation of Na-K
      ATPase and K permeability to the model show that our hypothesis predicts observed
      long-term ionic homeostasis. 

PMID- 24898590
TI  - Improving outcomes from ischaemic colitis: more questions than answers.

PMID- 24898589
TI  - Acid-sensing ion channels are involved in epithelial Na+ uptake in the rainbow
      trout Oncorhynchus mykiss.
AB  - A role for acid-sensing ion channels (ASICs) to serve as epithelial channels for
      Na(+) uptake by the gill of freshwater rainbow trout was investigated. We found
      that the ASIC inhibitors 4',6-diamidino-2-phenylindole and diminazene decreased
      Na(+) uptake in adult rainbow trout in a dose-dependent manner, with IC50 values
      of 0.12 and 0.96 MUM, respectively. Furthermore, we cloned the trout ASIC1 and
      ASIC4 homologs and demonstrated that they are expressed differentially in the
      tissues of the rainbow trout, including gills and isolated mitochondrion-rich
      cells. Immunohistochemical analysis using custom-made anti-zASIC4.2 antibody and
      the Na(+)-K(+)-ATPase (alpha5-subunit) antibody demonstrated that the trout ASIC
      localizes to Na(+)/K(+)-ATPase-rich cells in the gill. Moreover, three
      dimensional rendering of confocal micrographs demonstrated that ASIC is found in
      the apical region of mitochondrion-rich cells. We present a revised model whereby
      ASIC4 is proposed as one mechanism for Na(+) uptake from dilute freshwater in the
      gill of rainbow trout.

PMID- 24898587
TI  - Chronic opioids regulate KATP channel subunit Kir6.2 and carbonic anhydrase I and
      II expression in rat adrenal chromaffin cells via HIF-2alpha and protein kinase
      A.
AB  - At birth, asphyxial stressors such as hypoxia and hypercapnia are important
      physiological stimuli for adrenal catecholamine release that is critical for the
      proper transition to extrauterine life. We recently showed that chronic opioids
      blunt chemosensitivity of neonatal rat adrenomedullary chromaffin cells (AMCs) to
      hypoxia and hypercapnia. This blunting was attributable to increased ATP
      sensitive K(+) (KATP) channel and decreased carbonic anhydrase (CA) I and II
      expression, respectively, and involved MU- and delta-opioid receptor signaling
      pathways. To address underlying molecular mechanisms, we first exposed an O2- and
      CO2-sensitive, immortalized rat chromaffin cell line (MAH cells) to combined MU
      {[d-Arg(2),Ly(4)]dermorphin-(1-4)-amide}- and delta ([d-Pen(2),5,P-Cl
      Phe(4)]enkephalin)-opioid agonists (2 MUM) for ~7 days. Western blot and
      quantitative real-time PCR analysis revealed that chronic opioids increased KATP
      channel subunit Kir6.2 and decreased CAII expression; both effects were blocked
      by naloxone and were absent in hypoxia-inducible factor (HIF)-2alpha-deficient
      MAH cells. Chronic opioids also stimulated HIF-2alpha accumulation along a time
      course similar to Kir6.2. Chromatin immunoprecipitation assays on opioid-treated
      cells revealed the binding of HIF-2alpha to a hypoxia response element in the
      promoter region of the Kir6.2 gene. The opioid-induced regulation of Kir6.2 and
      CAII was dependent on protein kinase A, but not protein kinase C or calmodulin
      kinase, activity. Interestingly, a similar pattern of HIF-2alpha, Kir6.2, and
      CAII regulation (including downregulation of CAI) was replicated in chromaffin
      tissue obtained from rat pups born to dams exposed to morphine throughout
      gestation. Collectively, these data reveal novel mechanisms by which chronic
      opioids blunt asphyxial chemosensitivity in AMCs, thereby contributing to
      abnormal arousal responses in the offspring of opiate-addicted mothers.

PMID- 24898591
TI  - Drug-induced colonic Kaposi's sarcoma in a HIV-negative patient with ulcerative
      colitis: a case report and review of the literature.

PMID- 24898592
TI  - [Delirium].
AB  - Delirium in older patients is also associated with persistent functional and
      cognitive impairment. Nevertheless, it frequently remains unrecognized or
      misinterpreted by treating physicians and this is particularly true in cases of
      hypoactive delirium. Screening and assessment instruments are helpful in the
      identification of patients with delirium. A multifactorial model of a combination
      of predisposing and precipitating factors best explains the etiology of delirium
      and avoidance is crucial for its prevention. Whenever delirium is suspected,
      immediate diagnosis and therapy of the precipitating condition are of primary
      importance. Non-pharmacological interventions, for example environmental
      modifications, play an important role in managing behavioral symptoms of
      delirium. Pharmacological interventions are merely symptomatic and should be
      limited to patients with severe symptoms when non-pharmacological means fail. 

PMID- 24898593
TI  - Monitoring chronic diseases in Canada: the Chronic Disease Indicator Framework.
AB  - INTRODUCTION: The Public Health Agency of Canada developed the Chronic Disease
      Indicator Framework (the Framework) with the goal of systematizing and enhancing
      chronic disease surveillance in Canada by providing the basis for consistent and
      reliable information on chronic diseases and their determinants. METHODS:
      Available national and international health indicators, frameworks and national
      health databases were reviewed to identify potential indicators. To make sure
      that a comprehensive and balanced set of indicators relevant to chronic disease
      prevention was included, a conceptual model with "core domains" for grouping
      eligible indicators was developed. Specific selection criteria were applied to
      identify key measures. Extensive consultations with a broad range of government
      partners, non-governmental organizations and public health practitioners were
      conducted to reach consensus and refine and validate the Framework. RESULTS: The
      Framework contains 41 indicators organized in a model comprised of 6 core
      domains: social and environmental determinants, early life / childhood risk and
      protective factors, behavioural risk and protective factors, risk conditions,
      disease prevention practices, and health outcomes/status. Also planned is an
      annual release of updated data on the proposed set of indicators, including
      national estimates, breakdowns by demographic and socioeconomic variables, and
      time trends. CONCLUSIONS: Understanding the evidence related to chronic diseases
      and theirdeterminants is key to interpreting trends and crucial to the
      development of public health interventions. The Framework and its related
      products have the potential of becoming an indispensable tool for evidence
      informed decision making in Canada.

PMID- 24898588
TI  - MMP-14 is necessary but not sufficient for invasion of three-dimensional collagen
      by human muscle satellite cells.
AB  - The twenty-five known matrix metalloproteases (MMPs) and their endogenous
      inhibitors, tissue inhibitors of metalloproteases (TIMPs), mediate cell invasion
      through the extracellular matrix (ECM). In a comparative three-dimensional assay,
      we analyzed human and mouse satellite cells' competence to invade an artificial
      ECM (collagen I). We identified a single MMP that 1) is expressed by human muscle
      satellite cells; 2) is induced at the mRNA/protein level by adhesion to collagen
      I; and 3) is necessary for invasion into a collagen I matrix. Interestingly,
      murine satellite cells neither express this MMP, nor invade the collagen matrix.
      However, exogenous human MMP-14 is not sufficient to induce invasion of a
      collagen matrix by murine cells, emphasizing species differences. 

PMID- 24898595
TI  - The difference of predictors for recurrence after catheter ablation of non
      paroxysmal atrial fibrillation according to follow-up period.
AB  - The aim of this study was to assess the clinical and echocardiographic predictors
      for the recurrence of persistent atrial fibrillation (AF) after ablation during a
      long-term period.A total of 130 patients with persistent AF who had undergone
      radiofrequency catheter ablation (RFCA) were enrolled. We analyzed the relation
      between clinical parameters, echocardiographic parameters, and AF recurrences at
      6 months, 1 year, and 2 years after ablation.During the 2-year follow-up, AF
      recurred in 61 patients (46.6%). In the 6 month follow-up, AF recurrence was
      associated only with total ablation time only. However, during the 1-year and 2
      year follow-up periods, the presence of hypertension, impaired left atrial (LA)
      emptying fraction (eF) (<= 20%), decreased LA appendage (LAA) emptying velocity
      (<= 20 cm/sec), and LAAeF (<= 20%) were correlated with AF recurrence (odds ratio
      [OR] = 1.87, 2.45, 1.93, and 2.15 respectively, P = 0.016, 0.004, 0.029, and
      0.004 respectively). Among these factors, impaired LAeF was the only independent
      predictor of AF recurrence in multivariate analysis (OR = 2.81, P = 0.012).In
      patients with persistent AF who had undergone RFCA, the best predictor of AF
      recurrence after ablation varied according to the follow-up period. Diminished LA
      function was the only predictor of recurrence in the 2-year follow-up. Pre
      procedural assessment of LA function might be helpful in selecting those patients
      who would benefit from RFCA. 

PMID- 24898596
TI  - Six-minute walk distance is an independent predictor of hospital readmission in
      patients with chronic heart failure.
AB  - Patients with chronic heart failure (CHF) are frequently readmitted to the
      hospital due to disease progression. Although a shorter 6-minute walk distance
      (6MWD) is correlated with poor prognosis, 6MWD is not considered a clinical
      indicator for predicting hospital readmission.We investigated whether 6MWD
      measured at the time of hospital discharge predicted readmission due to heart
      failure in CHF patients.Patients admitted to the hospital for the first time due
      to heart failure were enrolled. After 6MWD was measured at discharge, patients
      were followed-up for 3 years. Clinical characteristics, 6MWD and readmission due
      to heart failure were evaluated in 252 patients (68.5 +/- 11.8 years old, 162
      males). Significant factors that affected readmission were extracted and cut-off
      values were determined using multivariate logistic regression analysis and
      receiver operating characteristic curves.Of 252 CHF patients, 103 were readmitted
      within 3 years. 6MWD at the time of discharge was significantly shorter in
      readmitted patients than non-readmitted patients (P < 0.001) and was a
      significant predictor of readmission (P < 0.001). The odds ratio for readmission
      was 1.22 (P < 0.001) with each 10-meter decrease in 6MWD. The 6MWD cut-off value
      was determined to be 390 meters, with a sensitivity of 0.75 and a specificity of
      0.77.6MWD measured at the time of discharge is an independent predictor of
      hospital readmission in CHF patients, with a cut-off value of 390 meters. 

PMID- 24898594
TI  - Optimisation of omalizumab dosage in patients with severe persistent allergic
      asthma using recoveryELISA.
AB  - BACKGROUND: The objective of this study was to investigate the suitability of
      recoveryELISA as a method to monitor treatment with therapeutic antibodies using
      the example of omalizumab. METHODS: The recoveryELISA is a newly developed
      immunoassay technology that measures three parameters in one test: the free level
      of antigen, the level of therapeutic antibody and the specific dose-response
      interaction which represents the actual activity of the drug. A retrospective and
      observational analysis was performed on 197 serum samples from 17 patients (13 +/
      4 years of age) with severe persistent allergic asthma who received add-on
      treatment with omalizumab. RESULTS: The mean omalizumab serum level during
      antibody therapy was 59 +/- 45 ug/mL; the kit's upper detection limit of 140
      ug/mL was exceeded in 27 samples. Antibody concentrations between 50 and 140
      ug/mL were found in 64 samples. Independent of the omalizumab dosage, nearly all
      measurements were in a range of absolute saturation as regards the IgE binding
      rate. Almost complete binding of IgE with a recovery of added labelled IgE of <1%
      was reached within a maximum of 11 days. CONCLUSIONS: The biochemical activity of
      therapeutic antibodies can be examined by recoveryELISA and their residual
      activity can be determined. Thus, further individualisation of therapy with
      biologics is possible using this test which seems to be suitable to diminish side
      effects and reduce costs.

PMID- 24898597
TI  - Arrhythmogenic right ventricular cardiomyopathy in pregnancy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly a
      genetically determined heart muscle disorder that is characterized by fibro-fatty
      replacement of the right ventricular (RV) myocardium.(1)) The clinical spectrum
      of ARVC may represent from asymptomatic premature ventricular complexes to
      ventricular tachycardia (VT) and sudden cardiac death (SCD). It is a well-known
      leading cause of SCD in young adults.(2,3))There is no general consensus on the
      management of ARVC in pregnancy, and the preferred mode of delivery is uncertain.
      Herein, we report a case of ARVC diagnosed at 20 weeks of gestation following a
      sustained VT and treated with an implantable cardiac defibrillator (ICD). We also
      reviewed the current knowledge and approach to ARVC in pregnancy since the
      literature on this condition is based on case reports. 

PMID- 24898599
TI  - IgG4-related cardiovascular disorders.
AB  - Immunoglobulin4 (IgG4)-related disease is a systemic inflammatory disease
      characterized by elevation of serum IgG4. It involves various organs such as the
      pancreas (autoimmune pancreatitis), lacrimal gland (Mikulicz's disease),
      retroperitoneum (retroperitoneal fibrosis), aorta (aortic aneurysm and aortitis),
      heart (constrictive pericarditis), and pseudotumors around the coronary arteries.
      These disorders often coexist in accordance with progression of the disease.
      Because IgG4-related cardiovascular disorder affects the patient's prognosis,
      early detection and treatment is important. Coronary CT imaging and
      echocardiography accidentally detect IgG4-related disorders and (18)FDG-PET
      imaging can identify active inflammation in the lesions. Measurement of serum
      IgG4 levels and tissue biopsy are necessary for diagnosis. Minor salivary gland
      biopsy is recommended even though (18)FDG uptake is not detected when it is
      difficult to obtain a biopsy specimen from IgG4-related cardiovascular lesions.
      The first-line treatment is high-dose corticosteroid therapy, however, relapse is
      often reported. Corticosteroids suppress the development of active inflammatory
      diseases such as aortitis, pericarditis, and pseudotumors, but already-developed
      lesions do not respond. A large developed aneurysm can rupture even during or
      after corticosteroid therapy, therefore, additional surgical treatment may be
      needed. Treatment of IgG4-related cardiovascular disorders might require higher
      doses of corticosteroids than IgG4-related extracardiovascular disorders. The
      adequate dose of corticosteroid, type and dose of immunosuppressant, and surgical
      intervention should be carefully considered on a case-by-case basis. 

PMID- 24898598
TI  - Validation of automated quantification of myocardial perfusion single-photon
      emission computed tomography using Heart Score View in patients with known or
      suspected coronary artery disease.
AB  - Heart Score View (HSV) is a free software package for automated quantification of
      myocardial single photon emission computed tomography (SPECT) imaging using a
      standard Windows computer. We compared scoring results of myocardial perfusion
      among visual analysis, Quantitative Perfusion SPECT (QPS), and HSV in patients
      with known or suspected coronary artery disease.This study included 75
      consecutive patients with known or suspected coronary artery disease who
      underwent adenosive stress-rest Tl-201 SPECT. Analysis of myocardial perfusion
      SPECT was performed on a standard 17-segment model visually and using QPS and
      HSV.There were 54 male and 21 female patients with a mean age of 70.5 +/- 10.7
      years. Thirteen patients (17%) had prior myocardial infarction. Summed stress
      score (SSS) and summed rest score (SRS) in the mid and basal areas were
      significantly higher on HSV than visual analysis or QPS. There was no significant
      difference in SDS in the whole area among the 3 methods. Similar results were
      found even in patients without prior myocardial infarction. Manual setting of the
      left ventricular cavity improved the correlations of SSS, SRS and SDS between HSV
      and the other methods.Our data suggested that HSV was comparable with visual
      analysis or QPS in scoring myocardial perfusion when manual setting of the left
      ventricular cavity is applied. 

PMID- 24898600
TI  - Sarpogrelate hydrochloride decreases cardio-ankle vascular index accompanied by
      increased serum lipoprotein lipase mass in type 2 diabetic patients.
AB  - The 5-hydroxytryptamine2A receptor antagonist sarpogrelate hydrochloride exerts
      its effect not only by inhibition of platelet aggregation, but also by some
      pleiotropic effects. We have reported that a low serum lipoprotein lipase (LPL)
      mass level reflects insulin resistance and may be a risk factor for
      atherosclerotic diseases. The aim of this prospective study was to clarify the
      effect of sarpogrelate on serum LPL mass and cardio-ankle vascular index (CAVI)
      as a marker related to arterial stiffness.Thirty-five type 2 diabetic patients
      (21 males and 14 females) with ankle brachial indices higher than 0.90 received
      sarpogrelate hydrochloride 300 mg/day for 6 months. Serum LPL mass and CAVI were
      measured during the study.After 6 months of sarpogrelate hydrochloride treatment,
      CAVI decreased significantly (10.11 +/- 0.92 to 9.87 +/- 0.97, P < 0.05) and
      serum LPL mass increased significantly (58.2 +/- 17.5 to 63.5 +/- 21.4, P <
      0.05). A negative correlation between change in CAVI and change in serum LPL mass
      was observed (r = -0.34, P < 0.05). Multiple regression analysis identified a
      change in serum LPL mass as a significant independent predictor for change in
      CAVI.We demonstrated that sarpogrelate hydrochloride decreased CAVI accompanied
      by increased serum LPL mass in type 2 diabetic patients. This result suggests
      that sarpogrelate hydrochloride improves arterial stiffness and is a potential
      treatment for diabetic angiopathy. 

PMID- 24898601
TI  - Comparison of medium-term results of transcatheter correction versus surgical
      treatment for secundum type atrial septal defect combined with pulmonary valve
      stenosis.
AB  - This study was undertaken to compare the clinical results of traditional surgery
      and a percutaneous procedure for secundum type atrial septal defect (ASD)
      combined with pulmonary valve stenosis (PS). A total of 78 consecutive patients
      were identified between March 2004 and July 2012 in our institution. Thirty-five
      patients (44.9%) underwent percutaneous correction and the remaining 43 patients
      (55.1%) were treated surgically. All patients had simultaneous complete
      correction in both groups and no serious complications occurred. The surgical
      group was significantly younger (13.9 +/- 13.0 versus 31.0 +/- 17.5 years, P <
      0.001) and had a longer mean hospital stay (12.6 +/- 4.7 versus 5.3 +/- 1.5 days,
      P < 0.001). There were no significant differences in defect size (18.0 +/- 7.9
      versus 16.9 +/- 8.4 mm, P = 0.553) and transvalvular gradient detected by
      transthoracic echocardiography (TTE) (74.7 +/- 28.3 versus 87.6 +/- 37.8 mmHg, P
      = 0.089) between the two groups. Significant tricuspid regurgitation (TR)
      decreased from 66% to 14% in the transcatheter group and from 40% to 9% in the
      surgical group. Mild pulmonary regurgitation was detected in 8 patients in the
      transcatheter cohort and in 6 patients in the surgical cohort after the
      procedure. At last follow-up, 83% and 93% of the patients in the transcatheter
      and surgical groups, respectively, were free of any symptoms, and a significant
      improvement from preprocedure was observed in the transcatheter group but not in
      the surgical group (P = 0.005 and P = 0.062). In conclusion, transcatheter
      correction is a valuable alternative to surgery and allows more patients to be
      effectively treated in China. 

PMID- 24898602
TI  - MiR-30b is involved in methylglyoxal-induced epithelial-mesenchymal transition of
      peritoneal mesothelial cells in rats.
AB  - Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMC) is
      a major contributor to the pathogenesis of peritoneal fibrosis. EMT is at least
      in part caused by repeated exposure to glucose degradation products (GDPs), such
      as methylglyoxal (MGO). MiRNA contributes greatly to the EMT of PMCs. In this
      study, we tried to profile whether differences exist between the peritoneal
      membrane (PM) miRNA expression seen in control rats and that seen in rats
      injected intraperitoneally with MGO. We assessed whether miR-30b has a possible
      role in MGO-induced EMT of PMCs in rats. Comparative miRNA expression array and
      real-time PCR analyses were conducted for the control group at the start of the
      experiment and for the MGO group after 1 and 2 weeks. During the second week, the
      MGO rats were treated with: a chemically modified antisense RNA oligonucleotide
      (ASO) complementary to the mature miR-30b (ASO group); an miR-30b mismatch
      control sequence (MIS group); or a citrate buffer (EMT group). Bioinformatic
      analyses indicated that the 3' untranslated region (3'-UTR) of bone morphogenetic
      protein 7 (BMP7) mRNA did contain a putative binding site for miR-30b. We also
      tried to investigate whether miR-30b targeted BMP7 in vitro by transfection. Of
      the upregulated miRNAs, miR-30b expression demonstrated the greatest increase.
      The administration of miR-30b ASO for two weeks significantly reduced alpha-SMA
      excretion and upregulated E-cadherin and BMP-7 expression. Our in vitro study
      showed that miR-30b directly targeted and inhibited BMP7 by binding to its 3'
      UTR. Our results revealed that miR-30b is involved in MGO-induced EMT of PMCs in
      rats.

PMID- 24898603
TI  - Estimation of skin optical parameters for real-time hyperspectral imaging
      applications.
AB  - Hyperspectral imaging combines high spectral and spatial resolution in one
      modality. This imaging technique is a promising tool for objective medical
      diagnostics. However, to be attractive in a clinical setting, the technique needs
      to be fast and accurate. Hyperspectral imaging can be used to analyze tissue
      properties using spectroscopic methods, and is thus useful as a general purpose
      diagnostic tool. We combine an analytic diffusion model for photon transport with
      real-time analysis of the hyperspectral images. This is achieved by parallelizing
      the inverse photon transport model on a graphics processing unit to yield optical
      parameters from diffuse reflectance spectra. The validity of this approach was
      verified by Monte Carlo simulations. Hyperspectral images of human skin in the
      wavelength range 400-1000 nm, with a spectral resolution of 3.6 nm and 1600
      pixels across the field of view (Hyspex VNIR-1600), were used to develop the
      presented approach. The implemented algorithm was found to output optical
      properties at a speed of 3.5 ms per line of image data. The presented method is
      thus capable of meeting the defined real-time requirement, which was 30 ms per
      line of data.The algorithm is a proof of principle, which will be further
      developed.

PMID- 24898605
TI  - Noninvasive and label-free determination of virus infected cells by Raman
      spectroscopy.
AB  - The present study demonstrates that Raman spectroscopy is a powerful tool for the
      detection of virus-infected cells. Adenovirus infection of human embryonic kidney
      293 cells was successfully detected at 12, 24, and 48 h after initiating the
      infection. The score plot of principal component analysis discriminated the
      spectra of the infected cells from those of the control cells. The viral
      infection was confirmed by the conventional immunostaining method performed 24 h
      after the infection. The newly developed method provides a fast and label-free
      means for the detection of virus-infected cells.

PMID- 24898604
TI  - Rotational multispectral fluorescence lifetime imaging and intravascular
      ultrasound: bimodal system for intravascular applications.
AB  - We report the development and validation of a hybrid intravascular diagnostic
      system combining multispectral fluorescence lifetime imaging (FLIm) and
      intravascular ultrasound (IVUS) for cardiovascular imaging applications. A
      prototype FLIm system based on fluorescence pulse sampling technique providing
      information on artery biochemical composition was integrated with a commercial
      IVUS system providing information on artery morphology. A customized 3-Fr bimodal
      catheter combining a rotational side-view fiberoptic and a 40-MHz IVUS transducer
      was constructed for sequential helical scanning (rotation and pullback) of
      tubular structures. Validation of this bimodal approach was conducted in pig
      heart coronary arteries. Spatial resolution, fluorescence detection efficiency,
      pulse broadening effect, and lifetime measurement variability of the FLIm system
      were systematically evaluated. Current results show that this system is capable
      of temporarily resolving the fluorescence emission simultaneously in multiple
      spectral channels in a single pullback sequence. Accurate measurements of
      fluorescence decay characteristics from arterial segments can be obtained rapidly
      (e.g., 20 mm in 5 s), and accurate co-registration of fluorescence and ultrasound
      features can be achieved. The current finding demonstrates the compatibility of
      FLIm instrumentation with in vivo clinical investigations and its potential to
      complement conventional IVUS during catheterization procedures.

PMID- 24898606
TI  - An organocatalytic one-pot cascade incorporating the Achmatowicz reaction
      affording 3-pyrone derivatives.
AB  - The development of an organocatalytic one-pot cascade for the annulation of
      simple starting materials: alpha,beta-unsaturated aldehydes, hydrogen peroxide,
      beta-carbonyl compounds and NBS to furnish optically active 3-pyrones in good
      yield and with excellent enantioselectivity is presented. Further diversification
      of the obtained products is demonstrated by selective reductive transformations. 

PMID- 24898607
TI  - Application of a sensitive and specific LC-MS/MS method for determination of
      eriodictyol-8-C-beta-d-glucopyranoside in rat plasma for a bioavailability study.
AB  - This study is the first to detail the development and validation of a rapid,
      sensitive and specific LC-ESI-MS/MS method for the determination of eriodictyol-8
      C-beta-d-glucopyranoside (EG) in rat plasma. A simple protein precipitation
      method was used for plasma sample preparation. Chromatographic separation was
      successfully achieved on an Agilent Zorbax XDB C18 column (2.1 * 50 mm, 3.5 um)
      using a step gradient program with the mobile phase of 0.1% formic acid aqueous
      solution and acetonitrile with 0.1% formic acid. EG and the internal standard
      (IS) were detected using an electrospray negative ionization mass spectrometry in
      the multiple reaction monitoring mode. This method demonstrated good linearity
      and did not show any endogenous interference with the active compound and IS
      peaks. The lower limit of quantification of EG was 0.20 ng/mL in 50 MUL rat
      plasma. The average recoveries of EG and IS from rat plasma were both above 80%.
      The inter-day precisions (relative standard deviation) of EG determined over 5
      days were all within 15%. The present method was successfully applied to a
      quantification and bioavailability study of EG in rats after intravenous and oral
      administration. The oral absolute bioavailability of EG in rats was estimated to
      be 7.71 +/- 1.52%.

PMID- 24898608
TI  - Multimodal nanoprobes evaluating physiological pore size of brain vasculatures in
      ischemic stroke models.
AB  - Ischemic stroke accounts for 80% strokes and originates from a reduction of
      cerebral blood flow (CBF) after vascular occlusion. For treatment, the first
      action is to restore CBF by thrombolytic agent recombinant tissue-type
      plasminogen activator (rt-PA). Although rt-PA benefits clinical outcome, its
      application is limited by short therapeutic time window and risk of brain
      hemorrhage. Different to thrombolytic agents, neuroprotectants reduce
      neurological injuries by blocking ischemic cascade events such as excitotoxicity
      and oxidative stress. Nano-neuroprotectants demonstrate higher therapeutic effect
      than small molecular analogues due to their prolonged circulation lifetime and
      disrupted blood-brain barrier (BBB) in ischemic region. Even enhanced BBB
      permeability in ischemic territories is verified, the pore size of ischemic
      vasculatures determining how large and how efficient the therapeutics can pass is
      barely studied. In this work, nanoprobes (NPs) with different diameters are
      developed. In vivo multimodal imaging indicates that NP uptakes in ischemic
      region depended on their diameters and the pore size upper limit of ischemic
      vasculatures is determined as 10-11 nm. Additionally, penumbra defined as
      salvageable ischemic tissues performed a higher BBB permeability than infarct
      core. This work provides a guideline for developing nano-neuroprotectants by
      taking advantage of the locally enhanced BBB permeability in ischemic brain
      tissues. 

PMID- 24898609
TI  - Aortic root replacement with a valve-sparing technique for quadricuspid aortic
      valve.
AB  - A 67-year old man with ascending aortic aneurysm was referred because of a
      quadricuspid aortic valve. He underwent aortic root replacement with a valve
      sparing technique. Under deep hypothermic circulatory arrest, replacement of the
      ascending aorta was successfully performed. The postoperative course was
      uneventful without recurrence of aortic regurgitation. 

PMID- 24898610
TI  - Paracetamol and ibuprofen block hydrothorax absorption in mice.
AB  - OBJECTIVES: Non-steroidal anti-inflammatory agents (NSAIDs) and paracetamol alter
      pleural permeability, hindering pleural fluid recycling. The aim of this study
      was to investigate the effect of different analgesic and anti-inflammatory agents
      on fluid recycling in an induced hydrothorax model in mice. METHODS: Hydrothorax
      was induced in C57BL/6 mice by injecting 500 MUl phosphate-buffered saline-bovine
      serum albumin 1% isosmotic in the right hemithorax. Paracetamol (1 g/kg),
      ibuprofen (250 mg/kg) and parecoxib (2 mg/kg) were administered systematically by
      intraperitoneal injections. Each drug group included eight mice, which were
      sacrificed at 2 h and 4 h, respectively, after injections. The remaining
      hydrothorax volume and total cells contained were determined. RESULTS: Regarding
      the paracetamol and ibuprofen groups, the remaining hydrothorax volume was
      greater than in the control group (350 +/- 61, 348 +/- 62 and 270 +/- 51 MUl,
      respectively, P = 0.042) when mice were sacrificed within 2 h. Similar
      observations were made in groups sacrificed after 4 h (202 +/- 45 and 198 +/- 44
      vs 107 +/- 56 MUl, respectively, P = 0.002). In the parecoxib group, the
      remaining hydrothorax volume was 122 +/- 53 MUl (P = 0.038 versus paracetamol and
      ibuprofen, P > 0.05 versus control group). At the same time, the absorption rate
      in the paracetamol and ibuprofen groups was lower than in the parecoxib and
      control groups (P = 0.033). In the parecoxib group, the absorption rate was lower
      than that in the control group after 2 h (P = 0.042). In the paracetamol and
      ibuprofen groups, the total cell count and the macrophage and the neutrophils
      counts were increased, compared with the control and parecoxib groups (P = 0.025,
      0.028 and 0.032, respectively). CONCLUSIONS: Paracetamol and ibuprofen acutely
      hinder pleural fluid recycling by lowering the fluid absorption rate (higher
      remaining hydrothorax volume), while they increased total white cell counts. COX
      2s presented lower remaining hydrothorax volume without acutely increasing the
      absorption rate. These findings could present some relevance to the
      administration of painkillers in patients with pleural effusion after
      thoracotomy.

PMID- 24898613
TI  - Mental health care among low-income pregnant women with depressive symptoms:
      facilitators and barriers to care access and the effectiveness of financial
      incentives for increasing care.
AB  - Access to mental health care is suboptimal for low-income pregnant women. Using
      in-depth interviews, we examined barriers and facilitators to accessing care
      among 42 low income pregnant women with depressive symptoms. To pilot whether
      financial incentives would increase utilization during pregnancy, half the women
      were randomized to receive $10 gift cards after mental health visits. Women
      reported external and internal barriers to accessing mental health care, and
      internal and interpersonal facilitators. Financial incentives did not impact how
      often the women visited mental health providers, suggesting that small incentives
      are not sufficient to catalyze mental health care use for this population. 

PMID- 24898612
TI  - Referral to Inpatient Treatment Does not Necessarily Imply a Need for Inpatient
      Treatment.
AB  - We analyzed the dispositional decisions taken in a unit for clinical decision
      making (UCDM) which was set up to examine all emergency inpatient referrals to a
      psychiatric hospital. Hospitalization proved unnecessary for at least 17 % of the
      N = 2,026 inpatient referrals over a one year period. Instead, these patients
      were admitted to day-hospitals or outpatient treatments, resulting in annual cost
      savings of approximately <euro>3.3 million. Merely 8 % of those non-admitted
      patients had to be hospitalized within 28 days of the decision for non-admission
      being taken. Thus, a specialized UCDM run by clinical experts can help identify
      cost-effective alternatives to hospitalization.

PMID- 24898611
TI  - Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse
      ESC differentiation without affecting naive to primed cell transition.
AB  - The differentiation of mouse embryonic stem cells (ESCs) is controlled by the
      interaction of multiple signaling pathways, typically mediated by post
      translational protein modifications. The addition of O-linked N-acetylglucosamine
      (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins
      is one such modification (O-GlcNAcylation), whose function in ESCs is only now
      beginning to be elucidated. Here, we demonstrate that the specific inhibition of
      O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and
      impairs differentiation of mouse ESCs both in serum-free monolayer and in
      embryoid bodies (EBs). Use of reporter cell lines demonstrates that Oga
      inhibition leads to a reduction in the number of Sox1-expressing neural
      progenitors generated following induction of neural differentiation as well as
      maintained expression of the ESC marker Oct4 (Pou5f1). In EBs, expression of
      mesodermal and endodermal markers is also delayed. However, the transition of
      naive cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and
      Dppa3 downregulation and Fgf5 upregulation remains unchanged. Finally, we
      demonstrate that increased O-GlcNAcylation results in upregulation of genes
      normally epigenetically silenced in ESCs, supporting the emerging role for this
      protein modification in the regulation of histone modifications and DNA
      methylation.

PMID- 24898614
TI  - Correlation of histologic regression in primary melanoma with sentinel node
      status.
AB  - IMPORTANCE: The influence of regression on the status of the sentinel node (SN)
      is controversial. In many centers, the presence of regression in thin melanomas
      supports the performance of an SN biopsy. OBJECTIVE: To identify whether
      regression in primary melanoma has any influence on SN involvement. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective study of melanomas with a Breslow
      thickness greater than 0.75 mm and undergoing SN biopsy from January 1, 2003,
      through December 31, 2010, at Instituto Valenciano de Oncologia, which receives
      melanoma patients from regional hospitals and dermatology practices. Only cases
      with paraffin blocks or histologic slides representative of the primary tumor and
      available for review were included in the study. Melanomas from 201 patients met
      these criteria and constitute the core of this study. EXPOSURES: Sentinel node
      biopsy in melanoma. MAIN OUTCOMES AND MEASURES: Presence or absence of regression
      in the primary melanoma, type (early vs late), and extension were correlated with
      the presence or absence of metastasis in the SNs. In addition, the main clinical
      and histologic characteristics of the primary melanoma were correlated with the
      status of SN and the regression features. RESULTS: Regression was found in 52
      melanomas (25.9%). Regression did not show a statistically significant
      association with SN status. When melanomas were subdivided by Breslow thickness
      into 4 groups, those with regression had a lower frequency of positive SNs in 3
      of the 4 groups (<=1.00, 1.01-2.00, and >4.00 mm), although differences did not
      reach statistical significance in any group. We found no influence by type of
      regression or its extension on the SN status. Regression was found more
      frequently in thin melanomas (<=1.00 mm), melanomas located on an axial site, and
      superficial spreading or lentigo maligna melanoma types (P = .02, P < .001, and P
      = .03, respectively). CONCLUSIONS AND RELEVANCE: Regression of the primary
      melanoma is not associated with a higher proportion of positive SNs. These data
      do not support the practice of performing SN biopsy in thin melanomas with
      regression in the absence of additional adverse prognostic characteristics.

PMID- 24898615
TI  - Sphingosine-1-phosphate promotes the differentiation of adipose-derived stem
      cells into endothelial nitric oxide synthase (eNOS) expressing endothelial-like
      cells.
AB  - BACKGROUND: Adipose tissue provides a readily available source of autologous stem
      cells. Adipose-derived stem cells (ASCs) have been proposed as a source for
      endothelial cell substitutes for lining the luminal surface of tissue engineered
      bypass grafts. Endothelial nitric oxide synthase (eNOS) is a key protein in
      endothelial cell function. Currently, endothelial differentiation from ASCs is
      limited by poor eNOS expression. The goal of this study was to investigate the
      role of three molecules, sphingosine-1-phosphate (S1P), bradykinin, and
      prostaglandin-E1 (PGE1) in ASC endothelial differentiation. Endothelial
      differentiation markers (CD31, vWF and eNOS) were used to evaluate the level of
      ASCs differentiation capability. RESULTS: ASCs demonstrated differentiation
      capability toward to adipose, osteocyte and endothelial like cell phenotypes.
      Bradykinin, S1P and PGE were used to promote differentiation of ASCs to an
      endothelial phenotype. Real-time PCR showed that all three molecules induced
      significantly greater expression of endothelial differentiation markers CD31, vWF
      and eNOS than untreated cells. Among the three molecules, S1P showed the highest
      up-regulation on endothelial differentiation markers. Immunostaining confirmed
      presence of more eNOS in cells treated with S1P than the other groups. Cell
      growth measurements by MTT assay, cell counting and EdU DNA incorporation suggest
      that S1P promotes cell growth during ASCs endothelial differentiation. The S1P1
      receptor was expressed in ASC-differentiated endothelial cells and S1P induced up
      regulation of PI3K. CONCLUSIONS: S1P up-regulates endothelial cell markers
      including eNOS in ASCs differentiated to endothelial like cells. This up
      regulation appears to be mediated by the up-regulation of PI3K via S1P1 receptor.
      ASCs treated with S1P offer promising use as endothelial cell substitutes for
      tissue engineered vascular grafts and vascular networks.

PMID- 24898616
TI  - Pyknotic cell death induced by Clostridium difficile TcdB: chromatin condensation
      and nuclear blister are induced independently of the glucosyltransferase
      activity.
AB  - TcdA and TcdB are the main pathogenicity factors of Clostridium difficile
      associated diseases. Both toxins inhibit Rho GTPases, and consequently, apoptosis
      is induced in the affected cells. We found that TcdB at higher concentrations
      exhibits cytotoxic effects that are independent on Rho glucosylation. TcdB and
      the glucosyltransferase-deficient mutant TcdB D286/288N induced pyknotic cell
      death which was associated with chromatin condensation and reduced H3
      phosphorylation. Affected cells showed ballooning of the nuclear envelope and
      loss of the integrity of the plasma membrane. Furthermore, pyknotic cells were
      positively stained with dihydroethidium indicating production of reactive oxygen
      species. In line with this, pyknosis was reduced by apocynin, an inhibitor of the
      NADPH oxidase. Bafilomycin A1 prevented cytotoxic effects showing that the newly
      observed pyknosis depends on intracellular action of TcdB rather than on a
      receptor-mediated effect. Blister formation and chromatin condensation was
      specifically induced by the glucosyltransferase domain of TcdB from strain
      VPI10473 since neither TcdBF from cdi1470 nor the chimera of TcdB harbouring the
      glucosyltransferase domain of TcdBF was able to induce these effects. In summary,
      TcdB induces two different and independent phenotypes: (i) cell rounding due to
      glucosylation of Rho GTPases and (ii) shrinkage of cells and nuclear blister
      induced by the high concentrations of TcdB independent of Rho glucosylation. 

PMID- 24898618
TI  - A facile approach for the preparation of tunable acid nano-catalysts with a
      hierarchically mesoporous structure.
AB  - A facile and efficient approach to prepare hierarchically and radially mesoporous
      nano-catalysts with tunable acidic properties has been successfully developed.
      The nanospheres show excellent catalytic performance for the acid catalysed
      reactions, i.e. cracking of 1,3,5-triisopropylbenzene and hydrolysis of sucrose. 

PMID- 24898617
TI  - Stilbenes and resveratrol metabolites improve mitochondrial fatty acid oxidation
      defects in human fibroblasts.
AB  - BACKGROUND: Inborn enzyme defects of mitochondrial fatty acid beta-oxidation
      (FAO) form a large group of genetic disorders associated to variable clinical
      presentations ranging from life-threatening pediatric manifestations up to milder
      late onset phenotypes, including myopathy. Very few candidate drugs have been
      identified in this group of disorders. Resveratrol (RSV) is a natural polyphenol
      with anti-oxidant and anti-inflammatory effects, recently shown to have
      beneficial metabolic properties in mice models. Our study explores its possible
      effects on FAO and mitochondrial energy metabolism in human cells, which are
      still very little documented. METHODS: Using cells from controls and from
      patients with Carnitine Palmitoyl Transferase 2 (CPT2) or Very Long Chain AcylCoA
      Dehydrogenase (VLCAD) deficiency we characterized the metabolic effects of RSV,
      RSV metabolites, and other stilbenes. We also focused on analysis of RSV uptake,
      and on the effects of low RSV concentrations, considering the limited
      bioavailability of RSV in vivo. RESULTS: Time course of RSV accumulation in
      fibroblasts over 48 h of treatment were consistent with the resulting stimulation
      or correction of FAO capacities. At 48 h, half maximal and maximal FAO
      stimulations were respectively achieved for 37,5 microM (EC50) and 75 microM RSV,
      but we found that serum content of culture medium negatively modulated RSV uptake
      and FAO induction. Indeed, decreasing serum from 12% to 3% led to shift EC50 from
      37,5 to 13 microM, and a 2.6-3.6-fold FAO stimulation was reached with 20 microM
      RSV at 3% serum, that was absent at 12% serum. Two other stilbenes often found
      associated with RSV, i.e. cis- RSV and piceid, also triggered significant FAO up
      regulation. Resveratrol glucuro- or sulfo- conjugates had modest or no effects.
      In contrast, dihydro-RSV, one of the most abundant circulating RSV metabolites in
      human significantly stimulated FAO (1.3-2.3-fold). CONCLUSIONS: This study
      provides the first compared data on mitochondrial effects of resveratrol, its
      metabolites, and other natural compounds of the stilbene family in human cells.
      The results clearly indicate that several of these compounds can improve
      mitochondrial FAO capacities in human FAO-deficient cells.

PMID- 24898620
TI  - Geriatric dentistry in the USA: looking back 30 years.

PMID- 24898619
TI  - ISWI remodels nucleosomes through a random walk.
AB  - The chromatin remodeler ISWI is capable of repositioning clusters of nucleosomes
      to create well-ordered arrays or moving single nucleosomes from the center of DNA
      fragments toward the ends without disrupting their integrity. Using standard
      electrophoresis assays, we have monitored the ISWI-catalyzed repositioning of
      different nucleosome samples each containing a different length of DNA
      symmetrically flanking the initially centrally positioned histone octamer. We
      find that ISWI moves the histone octamer between distinct and thermodynamically
      stable positions on the DNA according to a random walk mechanism. Through the
      application of a spectrophotometric assay for nucleosome repositioning, we
      further characterized the repositioning activity of ISWI using short nucleosome
      substrates and were able to determine the macroscopic rate of nucleosome
      repositioning by ISWI. Additionally, quantitative analysis of repositioning
      experiments performed at various ISWI concentrations revealed that a monomeric
      ISWI is sufficient to obtain the observed repositioning activity as the presence
      of a second ISWI bound had no effect on the rate of nucleosome repositioning. We
      also found that ATP hydrolysis is poorly coupled to nucleosome repositioning,
      suggesting that DNA translocation by ISWI is not energetically rate-limiting for
      the repositioning reaction. This is the first calculation of a microscopic ATPase
      coupling efficiency for nucleosome repositioning and also further supports our
      conclusion that a second bound ISWI does not contribute to the repositioning
      reaction. 

PMID- 24898621
TI  - Outcome in squamous cell carcinoma of the nasal vestibule: a single center
      experience.
AB  - BACKGROUND: The purpose of this study was to analyze the outcome of squamous cell
      carcinomas (SCCs) of the nasal vestibule and to identify factors predicting
      recurrence. METHODS: All patients treated between 1995 and 2012 were included in
      this study. Outcome was analyzed with respect to modality of therapy, age, sex,
      tobacco consumption, staging, surgical margins, and histological differentiation
      pattern. RESULTS: Thirty patients were included. Fourteen patients (47%) were
      found with T4, 1 patient (3%) with T3, 7 patients (23%) with T2, and 8 patients
      (27%) with T1 disease. Twenty-one patients (70%) were treated surgically. Six
      patients (29%) needed postoperative radiation because of insufficient surgical
      margins. Radiation was the first-line treatment in 9 patients (30%). Surgically
      treated patients with surgical margins <3 mm had significantly more locoregional
      recurrence compared to those with sufficient resections. CONCLUSION: Advanced T4
      carcinomas show a high recurrence rate. Insufficient surgical margins are the
      main predictor for a locoregional recurrence and should be avoided.

PMID- 24898622
TI  - Topical ivermectin versus crotamiton cream 10% for the treatment of scabies.
AB  - Scabies, known colloquially as the 7-year itch, is a contagious skin infection
      that occurs among humans and other animals. The treatment of choice is still
      controversial. The aim of this study was to compare the efficacy and safety of
      topical ivermectin vs. crotamiton cream 10% for the treatment of scabies. In
      total, 340 patients with scabies were enrolled, and randomized into two groups.
      The first group received 1% ivermectin applied topically to the affected skin.
      The dose employed was 400 MUg/kg, repeated once the following week, and the
      second group received crotamiton 10% cream and were told to apply this twice
      daily for five consecutive days. Treatment was evaluated at intervals of two and
      four weeks, and if there was treatment failure at the 2-week follow-up, treatment
      was repeated. Two applications of topical ivermectin provided a cure rate of
      64.7% at the 2-week follow-up, which increased to 82.3% at the 4-week follow-up
      after repeating the treatment. Treatment with single applications of crotamiton
      cream 10% was effective in 41.2% of patients at the 2-week follow-up, which
      increased to 64.7% at the 4-week follow-up after this treatment was repeated.
      Ivermectin was quite safe in our cases. Two applications of ivermectin were as
      effective as single applications of crotamiton 10% cream at the 2-week follow-up.
      After repeating the treatment, ivermectin was superior to crotamiton cream 10% at
      the 4-week follow-up. 

PMID- 24898623
TI  - Migraine-like headache with autonomic symptoms in midbrain malformation.
AB  - We report a case of midbrain malformation characterized by right deviation of the
      medulla oblongata associated with elongation and ectasia of the basilar and left
      vertebral arteries in a patient with a long history of migraine-like headache
      with autonomic symptoms. 

PMID- 24898626
TI  - Generation of proton aurora by magnetosonic waves.
AB  - Earth's proton aurora occurs over a broad MLT region and is produced by the
      precipitation of low-energy (2-10 keV) plasmasheet protons. Proton precipitation
      can alter chemical compositions of the atmosphere, linking solar activity with
      global climate variability. Previous studies proposed that electromagnetic ion
      cyclotron waves can resonate with protons, producing proton scattering
      precipitation. A long-outstanding question still remains whether there is another
      mechanism responsible for the proton aurora. Here, by performing satellite data
      analysis and diffusion equation calculations, we show that fast magnetosonic
      waves can produce trapped proton scattering that yields proton aurora. This
      provides a new insight into the mechanism of proton aurora. Furthermore, a ray
      tracing study demonstrates that magnetosonic wave propagates over a broad MLT
      region, consistent with the global distribution of proton aurora. 

PMID- 24898624
TI  - The prevalence of familial hemiplegic migraine with cerebellar ataxia and
      spinocerebellar ataxia type 6 in Portugal.
AB  - BACKGROUND: CACNA1A gene disorders present a variable familial phenotype of
      ataxia, migraine with aura, and/or hemiplegic migraine. Prevalence data for these
      conditions are scarce. OBJECTIVE: The aim of this study is to report a minimal
      prevalence estimate for familial hemiplegic migraine with cerebellar ataxia and
      spinocerebellar ataxia type 6 in Portugal. METHODS: This is a multisource
      population-based prevalence study. Patients and families with spinocerebellar
      ataxia type 6 and familial hemiplegic migraine and cerebellar ataxia identified
      through the Portuguese survey of hereditary ataxias and spastic paraplegias were
      re-evaluated. Prevalent patients were confirmed to be alive and affected at the
      1st of January 2013. RESULTS: One family with spinocerebellar ataxia type 6 and 2
      families with other CACNA1A gene mutations were identified. From these families,
      23 patients were alive and living in Portugal in the prevalence day, for an
      estimated national prevalence per 100,000 inhabitants of 0.21 for familial
      hemiplegic migraine with cerebellar ataxia and of 0.01 for spinocerebellar ataxia
      type 6. CONCLUSION: The prevalence of familial hemiplegic migraine with
      cerebellar ataxia and spinocerebellar ataxia type 6 are both probably low in
      Portugal.

PMID- 24898625
TI  - Nanostructured manganese oxide/carbon nanotubes, graphene and graphene oxide as
      water-oxidizing composites in artificial photosynthesis.
AB  - Herein, we report on nano-sized Mn oxide/carbon nanotubes, graphene and graphene
      oxide as water-oxidizing compounds in artificial photosynthesis. The composites
      are synthesized by different and simple procedures and characterized by a number
      of methods. The water-oxidizing activities of these composites are also
      considered in the presence of cerium(IV) ammonium nitrate. Some composites are
      efficient Mn-based catalysts with TOF (mmol O2 per mol Mn per second) ~ 2.6.

PMID- 24898627
TI  - Ophthalmic plastic and orbital surgery in Taiwan.
AB  - We describe in this paper the current status of ophthalmic plastic and orbital
      surgery in Taiwan. Data were collected from the Bureau of National Health
      Insurance of Taiwan, the Bulletin of the Taiwan Ophthalmic Plastic and
      Reconstructive Society, and the Statistics Yearbook of Practicing Physicians and
      Health Care Organizations in Taiwan by the Taiwan Medical Association. We
      ascertained that 94 ophthalmologists were oculoplastic surgeons and accounted for
      5.8% of 1621 ophthalmologists in Taiwan. They had their fellowship training
      abroad (most ophthalmologists trained in the United States of America) or in
      Taiwan. All ophthalmologists were well trained and capable of performing major
      oculoplastic surgeries. The payment rates by our National Health Insurance for
      oculoplastic and orbital surgeries are relatively low, compared to Medicare
      payments in the United States. Ophthalmologists should promote the concept that
      oculoplastic surgeons specialize in periorbital plastic and aesthetic surgeries.
      However, general ophthalmologists should receive more educational courses on
      oculoplastic and cosmetic surgery.

PMID- 24898628
TI  - Clinicopathological features, postoperative survival and prognostic variables for
      cancer-related survival in patients with mucinous colorectal carcinoma.
AB  - PURPOSE: To investigate the clinicopathological features and postoperative
      survival of patients with mucinous colorectal carcinoma (MC) and to identify the
      factors related to long-term survival. METHODS: Twenty-three patients who had
      undergone resection for MC at Miyazaki University Hospital from 1991 to 2006 were
      followed up for at least 5 years or until death. The effects of the
      clinicopathological variables on the 5-year cancer-specific survival were
      assessed by the univariate analyses. These patients' clinicopathological data
      were compared with those of 403 non-mucinous carcinoma (NMC) patients (102 well
      differentiated adenocarcinomas, 301 moderately differentiated adenocarcinomas).
      RESULTS: The 5-year cancer-specific survival rate was significantly worse in MC
      (56.2 %) than in NMC (73.8 %; p = 0.008) cases. Univariate analyses showed the T
      factor, lymph node metastases, liver metastases, metastases to the distant
      peritoneum, remote metastases and curative resection to be significant factors
      predicting the survival. However, there were no significant differences in the
      postoperative survival in patients with stage II-IV disease. The rates of
      metastases to the distant peritoneum, M1, T4, a tumor size >=5 cm and non
      curative resection were higher in MC than in NMC patients. CONCLUSIONS: Patients
      with MC had advanced stage cancer, especially with metastases to the distant
      peritoneum, more frequently than did the patients with NMC. To improve the
      survival of these patients, it is therefore important to detect MC at an early
      stage and to perform curative resection.

PMID- 24898630
TI  - Conformationally constrained cyclic peptides: powerful scaffolds for asymmetric
      catalysis.
AB  - Cyclic peptides containing a disulfide bridge were identified as a simple and
      versatile coordination sphere for asymmetric catalysis. Upon complexation with
      Cu(2+) ions they catalyze Diels-Alder and Friedel-Crafts reactions with high
      enantioselectivities of up to 99% ee and 86% ee, respectively. Moreover, the
      peptides ligands were systematically optimized with the assistance of "Alanine
      Scanning". This biomolecular design could greatly expand the choice of peptide
      scaffolds for artificial metallopeptide catalysts.

PMID- 24898629
TI  - Clinical application of navigation surgery using augmented reality in the
      abdominal field.
AB  - This article presents general principles and recent advancements in the clinical
      application of augmented reality-based navigation surgery (AR based NS) for
      abdominal procedures and includes a description of our clinical trial and
      subsequent outcomes. Moreover, current problems and future aspects are discussed.
      The development of AR-based NS in the abdomen is delayed compared with another
      field because of the problem of intraoperative organ deformations or the
      existence of established modalities. Although there are a few reports on the
      clinical use of AR-based NS for digestive surgery, sophisticated technologies in
      urology have often been reported. However, the rapid widespread use of video- or
      robot assisted surgeries requires this technology. We have worked to develop a
      system of AR-based NS for hepatobiliary and pancreatic surgery. Then we developed
      a short rigid scope that enables surgeons to obtain 3D view. We recently focused
      on pancreatic surgery, because intraoperative organ shifting is minimal. The
      position of each organ in overlaid image almost corresponded with that of the
      actual organ with about 5 mm of mean registration errors. Intraoperative
      information generated from this system provided us with useful navigation.
      However, AR-based NS has several problems to overcome such as organ deformity,
      evaluation of utility, portability or cost. 

PMID- 24898631
TI  - Behavioral medicine in China.

PMID- 24898632
TI  - Characterisation of a novel endo-xyloglucanase (XcXGHA) from Xanthomonas that
      accommodates a xylosyl-substituted glucose at subsite -1.
AB  - A xyloglucan-specific endo-1,4beta-glucanase (XcXGHA) from Xanthomonas citri pv.
      mangiferaeindicae has been cloned, expressed in Escherichia coli, purified and
      characterised. The XcXGHA enzyme belongs to CAZy family GH74 and has catalytic
      site residues conserved with other xyloglucanases in this family. At its optimal
      reaction conditions, pH 7.0 and 40  degrees C, the enzyme has a k cat/K M value
      of 2.2 * 10(7) min(-1) M(-1) on a tamarind seed xyloglucan substrate. XcXGHA is
      relatively stable within a broad pH range (pH 4-9) and up to 50  degrees C (t
      1/2, 50  degrees C of 74 min). XcXGHA is proven to be xyloglucan-specific, and a
      glycan microarray study verifies that XcXGHA catalyses cleavage of xyloglucan
      extracted from both monocot and dicot plant species. The enzyme catalyses
      hydrolysis of tamarind xyloglucan in a unique way by cleaving XXXG into XX and XG
      (X is xylosyl-substituted glucose; G is unsubstituted glucose), is able to
      degrade more complex xyloglucans and notably is able to cleave near more
      substituted xyloglucan motifs such as L [i.e. alpha-L-Fucp-(1 -> 2)-beta-D-Galp
      (1 -> 2)-alpha-D-Xylp-(1 -> 6)-beta-D-Glcp]. LC-MS/MS analysis of product
      profiles of tamarind xyloglucan which had been catalytically degraded by XcXGHA
      revealed that XcXGHA has specificity for X in subsite -1. The 3D model suggests
      that XcXGHA consists of two seven-bladed beta-propeller domains with the
      catalytic center formed by the interface of these two domains, which is conserved
      in xyloglucanases in the GH74 family. However, the XcXGHA has two amino acids
      (D264 and R472) that differ from the conserved residues of other GH74
      xyloglucanases. These two amino acids were predicted to be located on the
      opposite side of the active site pocket, facing each other and forming a closing
      surface above the active site pocket. These two amino acids may contribute to the
      unique substrate specificity of the XcXGHA enzyme.

PMID- 24898633
TI  - Surface analysis reveals biogenic oxidation of sub-bituminous coal by Pseudomonas
      fluorescens.
AB  - Direct analysis of the colonised surface on coal using attenuated total
      reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) revealed the
      nature of bacteria-mediated oxidation at the coal surface. Unique oxidation peaks
      generated by the presence of Pseudomonas fluorescens on coal was shown through
      ATR-FTIR measurements, and ATR-FTIR imaging illustrated that this peak was only
      observed within the region of coal colonised by bacteria. Contact angle
      measurements and surface free energy of adhesion calculations showed that the
      adhesion between P. fluorescens and coal was thermodynamically favourable, and
      scanning electron microscopy (SEM) exhibited individual cell or monolayer cluster
      attachment on coal. Furthermore, Gaussian peak fitting of peroxidase-treated coal
      ATR-FTIR spectra revealed that peroxidase or related enzymes produced by P.
      fluorescens may be responsible for coal oxidation. This study demonstrated the
      usefulness and practicality of ATR-FTIR for analysing coal oxidation by P.
      fluorescens and may well be applied to other microbe-driven modifications of coal
      for its rapidity and reliability. 

PMID- 24898634
TI  - Potentialities of coupling biological processes (biotrickler/biofilter) for the
      degradation of a mixture of sulphur compounds.
AB  - This study deals with the potential of biological processes combining a
      biotrickler and a biofilter to treat a mixture of sulphur-reduced compounds
      including dimethyl sulphide (DMS), dimethyl disulphide (DMDS) and hydrogen
      sulphide (H2S). As a reference, duplicated biofilters were implemented, and
      operating conditions were similar for all bioprocesses. The first step of this
      work was to determine the efficiency removal level achieved for each compound of
      the mixture and in a second step, to assess the longitudinal distribution of
      biodegradation activities and evaluate the total bacteria, Hyphomicrobium sp. and
      Thiobacillus thioparus densities along the bed height. A complete removal of
      hydrogen sulphide is reached at the start of the experiment within the first
      stage (biotrickler) of the coupling. This study highlighted that the coupling of
      a biotrickling filter and a biofilter is an interesting way to improve both
      removal efficiency levels (15-20% more) and kinetics of recalcitrant sulphur
      compounds such as DMS and DMDS. The total cell densities remained similar (around
      1 * 10(10) 16S recombinant DNA (rDNA) copies g dry packing material) for
      duplicated biofilters and the biofilter below the biotrickling filter. The
      relative abundances of Hyphomicrobium sp. and T. thioparus have been estimated to
      an average of 10 +/- 7.0 and 0.23 +/- 0.07%, respectively, for all biofilters.
      Further investigation should allow achieving complete removal of DMS by starting
      the organic sulphur compound degradation within the first stage and surveying
      microbial community structure colonizing this complex system.

PMID- 24898635
TI  - Regional fluorodeoxyglucose metabolism and instrumental activities of daily
      living across the Alzheimer's disease spectrum.
AB  - BACKGROUND: Impairment in instrumental activities of daily living (IADL) begins
      as individuals with amnestic mild cognitive impairment (MCI) transition to
      Alzheimer's disease (AD) dementia. IADL impairment in AD dementia has been
      associated with inferior parietal, inferior temporal, and superior occipital
      hypometabolism using 18F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET). OBJECTIVE: To investigate the relationship between regional FDG metabolism
      and IADL in clinically normal (CN) elderly, MCI, and mild AD dementia subjects
      cross-sectionally and longitudinally. METHODS: One hundred and four CN, 203 MCI,
      and 95 AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative
      underwent clinical assessments every 6 to 12 months for up to three years and
      baseline FDG PET. The subjective, informant-based Functional Activities
      Questionnaire was used to assess IADL. General linear models and mixed effects
      models were used, covarying for demographics, cognition, and behavior. RESULTS:
      The cross-sectional analysis revealed middle frontal and orbitofrontal
      hypometabolism were significantly associated with greater IADL impairment.
      Additionally, the interaction of diagnosis with posterior cingulate and with
      parahippocampal hypometabolism showed a greater decline in IADL performance as
      metabolism decreased for the AD dementia relative to the MCI group, and the MCI
      group relative to the CN group. The longitudinal analysis showed that baseline
      middle frontal and posterior cingulate hypometabolism were significantly
      associated with greater rate of increase in IADL impairment over time.
      CONCLUSION: These results suggest that regional synaptic dysfunction, including
      the Alzheimer-typical medial parietal and less typical frontal regions, relates
      to daily functioning decline at baseline and over time across the early AD
      spectrum.

PMID- 24898636
TI  - Bombycis excrementum reduces amyloid-beta oligomer-induced memory impairments,
      neurodegeneration, and neuroinflammation in mice.
AB  - Alzheimer's disease (AD) is the most common cause of progressive dementia and is
      characterized by memory impairments, neuronal death, and neuroinflammation. AD
      related pathophysiology is caused primarily by the presence of amyloid-beta
      oligomers (AbetaO). Recently, an increased focus has been directed toward natural
      compounds or medicinal extracts for the treatment of AD. Extracts from Bombycis
      excrementum (BE), which is composed of various bioactive constituents and
      mulberry leaves (the preferred food of silkworms), have been shown to possess
      anti-inflammatory, anti-diabetic, and anti-oxidative effects. Additionally,
      mulberry leaves exert anti-amyloidogenic action and neuroprotective effects
      against Abeta peptides but it is unknown whether BE has a therapeutic effect on
      AD-related pathologies. Therefore, the present study examined whether BE inhibits
      AbetaO-induced memory loss, neuronal death, and inflammation. Behavioral tests
      revealed that BE significantly ameliorated AbetaO-induced memory impairments and
      inhibited AbetaO-induced neuronal loss in cultured cells and the brains of mice.
      BE also significantly inhibited microgliosis and astrogliosis following intra
      hippocampal AbetaO injections in mice. Furthermore, BE significantly attenuated
      the release of nitric oxide from microglia and reduced AbetaO-induced S100-beta
      cytokine release from activated astrocytes. These results suggest that BE may be
      a candidate agent for the treatment of AD. 

PMID- 24898637
TI  - Motor effects of radio electric asymmetric conveyer in Alzheimer's disease:
      results from a cross-over trial.
AB  - We conducted a randomized, cross-over trial to investigate the feasibility,
      safety, and motor effects of brain stimulation with radio electric asymmetric
      conveyer (REAC) technique in patients with Alzheimer's disease (AD).
      Neuropostural optimization (NPO) and sham protocol were administered to 60
      patients from the nursing home and day care units of the Alzheimer Center Reina
      Sofia Foundation. The mean age was 84.1 (SD 7.9) years and 86.7% of the subjects
      were female. Motor measures were collected at baseline (T1), immediately (T2),
      seven (T3), and 11 days (T4) after treatment and, following cross-over,
      immediately (T5), seven (T6), and 11 (T7) days after treatment. Close safety
      surveillance was conducted from seven days before T1 to the end of the study
      (T7), with total study duration of 35 days. Wilcoxon test was utilized in the
      efficacy analysis, considering T1 and T5 as independent baseline assessments and
      using a threshold of p < 0.05 (corrected) for statistical significance. The NPO
      protocol was easily administered and well accepted by the participants. Axial
      movements improved at T3 and T4 after NPO and at T2 after sham NPO, but no
      significant effects were observed in axial movements in the second phase of the
      trial. The effects of NPO in gait performance were not consistent. There were six
      falls between T2 and T7, but only two of them occurred in patients who had
      received NPO. In light of safety and feasibility of REAC, a trial with the more
      intense neuropsycho-physical optimization protocol is warranted. 

PMID- 24898638
TI  - Metabolomic signatures in peripheral blood associated with Alzheimer's disease
      amyloid-beta-induced neuroinflammation.
AB  - Discovery of biomarkers in peripheral blood is a crucial step toward the early
      diagnosis and repetitive monitoring of treatment response for Alzheimer's disease
      (AD). Metabolomics is a promising technology that can identify unbiased
      biomarkers. To explore potential blood biomarkers for AD via metabolic profiling
      with high-resolution magic angle spinning nuclear magnetic resonance techniques,
      we identified changes in peripheral blood metabolomic profiles in response to
      amyloid-beta (Abeta)-induced neuroinflammation and co-treatment with gallate, a
      phytochemical known to have anti-neuroinflammatory properties. Alzheimer's-like
      (AL) model mice were produced by intracerebroventricular infusion of Abeta and
      compared with normal control mice with infusion of vehicle. AL mice were treated
      with either gallate (treated AL mice) or vehicle (untreated AL mice). Metabolomic
      analyses of both whole blood and plasma showed a clear separation between
      untreated AL mice and the other two groups, with levels of several metabolites
      involved in energy metabolism, including pyruvate and creatine, being
      significantly reduced in untreated AL mice compared with control and treated AL
      mice. Gallate treatment suppressed Abeta-induced overproduction of the
      inflammatory cytokine tumor necrosis factor-alpha in the hippocampus and
      normalized plasma levels of the affected metabolites. These results suggest that
      plasma levels of several metabolites could be indicative of both brain pathology
      and therapeutic responses, supporting the possibility of a close relationship
      between central neuroinflammation and systemic metabolic disturbance. These
      findings also suggest the potential of NMR-based metabolomics as a method to
      identify novel plasma biomarkers for AD, which could be confirmed by future
      translational research with human patients. 

PMID- 24898639
TI  - Does preoperative mild cognitive impairment predict postoperative cognitive
      dysfunction after on-pump coronary bypass surgery?
AB  - BACKGROUND: Mild cognitive impairment (MCI) may contribute to the development of
      postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting
      (CABG). OBJECTIVE: The aim of this study was to investigate the incidence of
      early and long-term POCD after CABG in coronary heart disease patients with and
      without preoperative MCI. METHODS: The study enrolled two groups of males with
      coronary heart disease: 51 without MCI (mean age 56.0 +/- 6.42 years) and 50 with
      MCI (mean age 56.4 +/- 5.55 years). Baseline clinical characteristics as well as
      durations of cardiopulmonary bypass and aortic cross-clamping were similar
      between the two groups. MCI was defined as a Mini-Mental State Examination score
      of less than 28. All patients underwent detailed neuropsychological examinations
      (12 tests) before and 7-10 days and 1 year after surgery. The incidence of early
      and long-term POCD was estimated on the basis of criteria defined as a 20%
      decline on 20% of the tests. RESULTS: Early POCD was diagnosed in 72% of cases in
      patients with MCI and in 79% of those without MCI (p = 0.5; odds ratio [OR] =
      0.68; 95% confidence interval [CI] 0.2-2.2). Long-term POCD was diagnosed in 72%
      of MCI patients and in 70% of non-MCI patients (p = 0.8); OR = 1.08 (95% CI 0.4
      2.9). CONCLUSIONS: Our results show that the presence of MCI is not the leading
      cause of either early or long-term POCD in patients undergoing CABG. Further
      research should focus on the contribution of important clinical factors,
      including progression of atherosclerosis and adherence, to post-CABG POCD.

PMID- 24898640
TI  - Rates of formal diagnosis in people screened positive for dementia in primary
      care: results of the DelpHi-Trial.
AB  - BACKGROUND: Primary data about rates of formal diagnosis of dementia in the
      German primary care sector are widely lacking. OBJECTIVES: Main objectives are to
      analyze the rate of syndrome diagnosis in primary care patients who screened
      positive for dementia, the distribution of differential diagnoses, and factors
      associated with undiagnosed dementia. METHODS: DelpHi-MV (Dementia: life- and
      person-centered help in Mecklenburg-Western Pomerania) is an ongoing general
      practitioner (GP)-based, randomized, controlled intervention trial. A total of
      4,064 patients (>=70 years, living at home) recruited from 108 participating GP
      practices were screened for dementia (DemTect < 9). Of 692 eligible patients
      (17%), a total of 406 subjects (59%) provided informed consent. Present analyses
      are based on the data of 243 patients with complete baseline assessment on
      January 1, 2014 (preliminary data). Formal diagnoses were retrieved from the
      medical records of the treating GPs. A conditional fixed effect regression
      analysis was performed to analyze factors associated with undiagnosed dementia.
      RESULTS: A total of 40% of patients who screened positive for dementia had been
      formally diagnosed with dementia. Unspecified dementia was diagnosed in 53%,
      vascular dementia in 24%, and Alzheimer's disease in 19% of these patients.
      Undiagnosed dementia was significantly associated with a higher mean score in the
      Mini-Mental State Examination (odds ratio, 1.11; p < 0.01, 95% confidence
      interval 1.04-1.18). CONCLUSIONS: The diagnosis rate of dementia in German
      primary care (40%) is well within the range of the international data (20-50%).
      The results emphasize the need for action to enhance recognition and differential
      diagnosis of dementia.

PMID- 24898641
TI  - Baseline predictors of cognitive decline in patients with cerebral small vessel
      disease.
AB  - INTRODUCTION: Cerebral small vessel disease (SVD) is a common cause of cognitive
      impairment and vascular dementia. OBJECTIVE: We aimed to investigate predictors
      of cognitive decline in patients with SVD who initially presented with first-ever
      small subcortical stroke of lacunar type but had normal cognitive status.
      METHODS: A total of 294 patients with SVD were evaluated 3-5 years after initial
      presentation. We analyzed baseline demographic data, vascular risk factors,
      functional status expressed as score on modified Rankin Scale, total number of
      lacunar infarcts, and severity of white matter hyperintensities (WMH) on magnetic
      resonance imaging with Age-Related White Matter Changes scale total score
      (tARWMC) and Fazekas scale periventricular and deep subcortical scores. RESULTS:
      At follow-up, vascular cognitive impairment (VCI) on any type was detected in 188
      (63.9%) of SVD patients, with 65 (22.1%) meeting criteria for vascular dementia
      and 123 (41.8%) presenting with cognitive impairment not dementia. Patients with
      VCI were older (64.4 +/- 10.3 in VCI versus 58.6 +/- 10.5 years in non-VCI; p <
      0.0001) at the time of initial clinical presentation and more frequently male
      (57.9% VCI versus 46.2% non-VCI; p = 0.052). No difference was noted in frequency
      of vascular risk factors in VCI versus non-VCI cases. Multivariate logistic
      regression analysis adjusted by age and gender identified overall severity of WMH
      (tARWMC HR 1.42, 95% CI 1.01-2.00; p0.043) and total number of lacunar infarcts
      (HR 3.06, 95% CI 1.71-5.50, p < 0.001) as independent predictors of cognitive
      decline. CONCLUSION: In patients with SVD, independent predictors of VCI were
      baseline severity of WMH and total number of lacunar infarcts.

PMID- 24898642
TI  - Cholinesterase inhibition in Alzheimer's disease: is specificity the answer?
AB  - Cholinesterase inhibitors are the standard of care for Alzheimer's disease (AD).
      Acetylcholinesterase (AChE) catalyzes the hydrolysis of the cholinergic
      neurotransmitter acetylcholine. However, the related enzyme butyrylcholinesterase
      (BuChE) also breaks down acetylcholine and is likewise targeted by the same
      clinical cholinesterase inhibitors. The lack of clinical efficacy for the highly
      specific and potent AChE inhibitor, (-) huperzine A, is intriguing, given the
      known cholinergic deficit in AD. Based on the proven efficacy of inhibitors
      affecting both cholinesterases and the apparent failure of specific AChE
      inhibition, focused BuChE inhibition seems important for more effective treatment
      of AD. Therefore, BuChE-selective inhibitors provide promise for improved
      benefit. 

PMID- 24898643
TI  - The ASCOMALVA (Association between the Cholinesterase Inhibitor Donepezil and the
      Cholinergic Precursor Choline Alphoscerate in Alzheimer's Disease) Trial: interim
      results after two years of treatment.
AB  - Cholinesterase inhibitors (ChE-Is) are used for symptomatic treatment of mild-to
      moderate Alzheimer's disease (AD), but long-term effects of these compounds are
      mild and not always obvious. Preclinical studies have shown that combination of
      ChE-Is and the cholinergic precursor choline alphoscerate increases brain
      acetylcholine levels more effectively than single compounds alone. ASCOMALVA
      (Effect of association between a ChE-I and choline alphoscerate on cognitive
      deficits in AD associated with cerebrovascular injury) is a double-blind trial
      investigating if the ChE-I donepezil and choline alphoscerate in combination are
      more effective that donepezil alone. The trial has recruited AD patients
      suffering from ischemic brain damage documented by neuroimaging and has completed
      2 years of observation in 113 patients of the 210 planned. Patients were randomly
      allotted to an active treatment group (donepezil + choline alphoscerate) or to a
      reference group (donepezil + placebo). Cognitive functions were assessed by the
      Mini-Mental State Evaluation and Alzheimer's Disease Assessment Scale Cognitive
      subscale. Daily activity was evaluated by the basic and instrumental activities
      of daily living tests. Behavioral symptoms were assessed by the Neuropsychiatric
      Inventory. Over the 24-month observation period, patients of the reference group
      showed a moderate time-dependent worsening in all the parameters investigated.
      Treatment with donepezil plus choline alphoscerate significantly slowed changes
      of the different items analyzed. These findings suggest that the combination of
      choline alphoscerate with a ChE-I may prolong/increase the effectiveness of
      cholinergic therapies in AD with concomitant ischemic cerebrovascular injury. 

PMID- 24898644
TI  - Impact of N-Acetylcysteine on cerebral amyloid-beta plaques and kidney damage in
      spontaneously hypertensive stroke-prone rats.
AB  - BACKGROUND: Cerebral small vessel disease (CSVD) in spontaneously hypertensive
      stroke prone rats (SHRSP) is accompanied by parenchymal amyloid-beta (Abeta)
      deposition in the brain and by hypertensive nephropathy with tubulointerstitial
      damage. N-acetylcysteine (NAC) promotes blood-brain barrier (BBB) breakdown in
      SHRSP and may thus accelerate the failure of vascular and perivascular clearance
      of Abeta. OBJECTIVE: In this study, we test the hypothesis that treatment with
      NAC increases the cerebral Abeta load and improves renal damage in the SHRSP
      model. METHODS: A total of 46 SHRSP (ages 18-44 weeks) were treated daily with
      NAC (12 mg/kg body weight) and 74 no-treated age-matched SHRSP served as
      controls. The prevalence of parenchymal Abeta load, IgG positive small vessels,
      and small perivascular bleeds was assessed in different brain regions.
      Tubulointerstitial kidney damage was assessed through a) the presence of
      erythrocytes in peritubular capillaries and b) tubular protein cylinders.
      RESULTS: SHRSP treated with NAC had an age-dependent increase of BBB breakdown
      (assessed by the presence of IgG positive small vessels) and small perivascular
      bleeds, mainly in the cortex. NAC significantly increased the Abeta plaque load
      in the cortex while the number of parenchymal amyloid deposits in the remaining
      brain areas including basal ganglia, hippocampus, thalamus, and corpus callosum
      were unchanged. There were no significant treatment effects on tubulointerstitial
      kidney damage. CONCLUSION: The impact of NAC on cerebral cortical plaque load
      increase may result from the vascular pathology of SHRSP that accompanies BBB
      breakdown, leading to the failure of amyloid clearance mechanisms. It remains to
      be seen whether in humans chronic NAC intake may increase amyloid load in the
      aging human brain and dementia.

PMID- 24898645
TI  - Vitamin D is not associated with cognitive status in a cohort of very old
      hospitalized patients.
AB  - BACKGROUND/OBJECTIVE: The association between vitamin D levels and cognitive
      function remains a controversial issue especially in the very old, highly
      comorbid patients. We address the relative contribution of vitamin D when taking
      into account potential confounders well known to be involved in cognitive
      decline. METHODS: We investigated, in a prospective study of 428 very old
      inpatients from the Geneva geriatric hospital (mean age 85.2 y +/- 6.8; 74.1%
      women), the association between 25-hydroxyvitamin D (25(OH)D) levels with
      dementia and mild cognitive impairment (MCI), taking into account comorbid
      conditions, functionality, malnutrition, ApoE genotype, vitamin B12, calcium, and
      albumin as independent variables. RESULTS: 25(OH)D level was not different
      between the cognitively normal (n = 200), MCI (n = 46), and demented (n = 182)
      patients nor between the different etiologies of dementia. In polytomous logistic
      regression, the 25(OH)D level neither as a continuous variable nor as a
      categorical variable increased the risk to be MCI or demented. The 25(OH)D level
      did not predict conversion from normal or MCI to dementia in the 315 subjects who
      completed the 2 years follow-up. No changes were observed in the full adjusted
      model after taking into account the independent variables. Similarly, considering
      only the group of cognitively normal subjects, the 25(OH)D level was not
      associated with impairment of specific cognitive domain. CONCLUSION: In this
      cohort of old hospitalized patients with a high burden of comorbidities, the
      25(OH)D level alone or adjusted for confounders is not associated with cognitive
      status and did not predict conversion to dementia.

PMID- 24898646
TI  - The influence of co-morbidity and frailty on the clinical manifestation of
      patients with Alzheimer's disease.
AB  - Co-morbidity and frailty are common in Alzheimer's disease (AD) and may
      contribute to the heterogeneity in clinical manifestations of the disease. We
      cross-sectionally investigated whether co-morbidity and frailty were
      independently associated with the clinical manifestation of AD in the 4C-Dementia
      study; a multicenter, longitudinal study in newly diagnosed AD patients. Clinical
      manifestation was operationalized using a composite of cognitive performance
      (neuropsychological assessment), activities of daily living (Disability
      Assessment for Dementia; DAD) and neuropsychiatric symptoms (Neuropsychiatric
      Inventory). As predictors of prime interest, co-morbidity was determined using
      the Cumulative Illness Rating Scale (CIRS-G) and frailty by the Fried criteria.
      In total, 213 AD patients participated (mean age 75 +/- 10 years; 58% females).
      In linear regression models adjusted for age, gender, education, and disease
      duration, CIRS-G (beta = -0.21, p < 0.01) and frailty (beta = -0.34, p < 0.001)
      were separately associated with clinical AD manifestation. However, CIRS-G (beta
      = -0.12, p = 0.12) lost statistical significance when both were combined
      (frailty: beta = -0.31, p < 0.001). Models with the individual components of
      clinical AD manifestation as dependent variables show significant associations
      between cognitive performance and CIRS-G (beta = -0.22, p = 0.01), and between
      DAD and frailty (beta = -0.37, p < 0.001). Our findings indicate that physical
      health and clinical AD manifestation are associated. This association may be
      responsible for part of the heterogeneity in the presentation of AD. This
      emphasizes the importance of adequate assessment of co-morbid medical conditions
      and frailty in patients with AD. 

PMID- 24898647
TI  - A case of logopenic primary progressive aphasia with C9ORF72 expansion and
      cortical florbetapir binding.
AB  - We report the case of a 65-year-old woman, clinically diagnosed with the
      logopenic variant of primary progressive aphasia (PPA), and carrier of C9ORF72
      expansion, despite cerebrospinal fluid biomarkers suggesting Alzheimer's disease
      (AD). She underwent structural MRI, metabolic PET, and amyloid PET imaging using
      florbetapir. Comparison with healthy controls revealed widespread hypometabolism,
      left sided cortical atrophy, and an increased cortical amyloid load. No
      difference in amyloid binding was found between the patient and predemential AD
      patients. This case provides evidence of amyloidopathy in a carrier of C9ORF72
      expansion exhibiting a clinical profile of the logopenic variant of PPA. 

PMID- 24898648
TI  - Alzheimer's disease-like pattern of (18)F-FDG uptake during a hyperglycemic state
      and negative (11)C-PiB binding in a patient with mild cognitive impairment.
AB  - Increased plasma glucose levels can cause the regional reduction of fluorine-18
      labeled fluorodeoxyglucose (18F-FDG) uptake in the posterior cingulate,
      precuneus, and/or temporoparietal cortices as an Alzheimer's disease (AD)-like
      pattern. However, the association of such an AD-like pattern of cerebral 18F-FDG
      uptake with AD pathophysiology is unknown. We report a case of a 70-year-old
      patient with mild cognitive impairment, and show that the AD-like pattern of
      cerebral 18F-FDG uptake during a hyperglycemic state could be reversible and is
      not associated with amyloid-beta accumulation. Our case concludes that the AD
      like pattern is dependent on the plasma glucose level and independent of AD
      pathophysiology. 

PMID- 24898649
TI  - Autonomic dysfunction in Alzheimer's disease: tools for assessment and review of
      the literature.
AB  - Autonomic dysfunction is very common in patients with dementia, and its presence
      might also help in differential diagnosis among dementia subtypes. Various
      central nervous system structures affected in Alzheimer's disease are also
      implicated in autonomic nervous system regulation, and it has been hypothesized
      that the deficit in central cholinergic function observed in Alzheimer's disease
      could likely lead to autonomic dysfunction. Several feasible tests can be used in
      clinical practice for the assessment of parasympathetic and sympathetic
      functions, especially in terms of cardiovascular autonomic modulation. In this
      review, we describe the different tests available and the evidence from the
      literature which indicate a definite presence of autonomic dysfunction in
      dementia at various degrees. Importantly, the recognition of dysautonomia,
      besides possibly being an early marker of dementia, would help prevent the
      disabling complications which increase the risk of morbidity,
      institutionalization, and mortality in these individuals. 

PMID- 24898650
TI  - Modulation of amyloid-beta protein precursor expression by HspB1.
AB  - Upregulation of heat shock proteins, such as Hsp70 and HspB1/Hsp27, have been
      associated with an amelioration of the deficits in animal models of Alzheimer's
      disease (AD). HspB1 is reported to be increased in AD brains and to accumulate in
      plaques, but whether this localization is an attempt by HspB1 to ameliorate the
      detrimental effects of amyloid-beta (Abeta) on cells or part of the disease
      process is unknown. Here we explore the potential effects of the HspB1 on amyloid
      beta protein precursor (AbetaPP) processing and distribution within HEK293 stable
      cell lines expressing either AbetaPPwt or AbetaPPsw. We compare AbetaPP
      production, distribution, and release of proteolytic products (including Abeta40
      and Abeta42) to determine possible modifications in the presence of HspB1. We
      also investigate whether HspB1 interacts with Abeta or its precursor, AbetaPP,
      and whether, through this interaction, it is able to alter AbetaPP processing or
      release of Abeta peptide. Coexpression of HspB1 resulted in increased cellular
      holoAbetaPP as well as C-terminal fragments. Further, expression of HspB1
      attenuated the release of Abeta42 from the AbetaPPsw cells. In summary, we have
      shown that expression of HspB1 alters AbetaPP expression and processing in cell
      lines expressing AbetaPPwt and AbetaPPsw. Furthermore, the presence of HspB1
      decreased the amount of Abeta42 released by the cell lines. Thus in addition to
      its effects on protecting cells from the potentially toxic effects of Abeta,
      HspB1 also appears to be involved in modulating cellular levels of AbetaPP,
      although an understanding of the underlying mechanisms requires further
      investigation. 

PMID- 24898651
TI  - Psychosis in frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is a neurodegenerative disorder, associated with a
      progressive decline in behavior caused by focal degeneration of the frontal
      lobes. Psychosis was an underestimated symptom of FTD, however, recent genetic
      research has revealed a high prevalence of psychosis in certain genetic groups.
      The primary objective of this work is to review the literature on psychosis in
      FTD and to propose directions for future research, with reference to findings on
      psychosis in schizophrenia. A search was performed using PubMed, MEDLINE, and
      EMBASE. Search terms included "frontotemporal dementia", "psychosis",
      "schizophreni*", "psychotic symptoms", "hallucinations", and "delusions", and it
      identified 122 articles. Results revealed: 1) prevalence is approximately 10%, 2)
      TDP-43 type B and FUS pathologies might have relatively high frequency of
      psychosis, 3) psychosis in FTD is higher with genetic mutations of C9ORF72 and
      GRN, 4) imaging researches did not achieve conclusive results, and 5) no
      treatment for psychosis in FTD is currently available. A limitation of this
      systematic review is that it includes a small number of studies specifically
      examining psychosis in FTD. It is suggested that a possible overlap exists
      between FTD and schizophrenia. This potential overlap indicates a vulnerability
      to psychosis due to brain systems and pathways shared by these disorders. 

PMID- 24898652
TI  - Cognitive enhancers (Nootropics). Part 1: drugs interacting with receptors.
      Update 2014.
AB  - Scientists working in the fields of Alzheimer's disease and, in particular,
      cognitive enhancers are very productive. The review "Cognitive enhancers
      (nootropics): drugs interacting with receptors" was accepted for publication in
      July 2012. Since then, new targets for the potential treatment of Alzheimer's
      disease were identified. This update describes drugs interacting with 42
      receptors versus 32 receptors in the first paper. Some compounds progressed in
      their development, while many others were discontinued. The present review covers
      the evolution of research in this field through March 2014. 

PMID- 24898653
TI  - A nutritional approach to ameliorate altered phospholipid metabolism in
      Alzheimer's disease.
AB  - Recently, a biomarker panel of 10 plasma lipids, including 8 phosphatidylcholine
      species, was identified that could predict phenoconversion from cognitive normal
      aged adults to amnestic mild cognitive impairment or Alzheimer's disease (AD)
      within 2-3 years with >90% accuracy. The reduced levels of these plasma
      phospholipids could reflect altered phospholipid metabolism in the brain and
      periphery. We show that a 24-week nutritional intervention in drug-naive patients
      with very mild to mild AD significantly increased 5 of the 7 measured biomarker
      phosphatidylcholine species. By providing nutrients which normally rate-limit
      phospholipid synthesis, this nutritional intervention could be useful in
      asymptomatic subjects with a plasma lipid biomarker profile prognostic of AD. 

PMID- 24898654
TI  - The probable auto-antigenic role of lipids (anti-ganglioside antibodies) in the
      pathogenesis of Alzheimer's disease.
AB  - We examined the sera of 103 demented patients of a mean age of 75 years and 60
      age-matched healthy individuals, using ELISA, to investigate the levels of IgM
      antibodies against GM1, GD1b, and GQ1b gangliosides and their possible
      correlation with clinical parameters (age, severity, and type of dementia). All
      the individuals that demonstrated positive titers of anti-ganglioside antibodies
      were demented patients whereas normal controls showed borderline or negative
      values. Significant correlation was revealed between IgM anti-GM1 and both the
      age of the patients and the severity of dementia. Most of the patients with
      increased IgM anti-GD1b titers suffered from AD. 

PMID- 24898655
TI  - Oophorectomy and hysterectomy may increase dementia risk but only when performed
      prematurely.

PMID- 24898656
TI  - Oophorectomy, hysterectomy, and risk of Alzheimer's disease: a nationwide case
      control study.
AB  - BACKGROUND: Association between oophorectomy and/or hysterectomy and dementia in
      context of hormone therapy (HT) use is ambiguous. OBJECTIVE: To assess whether
      oophorectomy, hysterectomy, and hysterectomy with bilateral oophorectomy are
      related to risk of Alzheimer's disease (AD), whether the possible indication for
      surgery plays a role, and if the associations are modified by HT. METHODS: Our
      nationwide register based case-control (1 : 1) study included all women with
      clinically-verified AD diagnoses, residing in Finland on December 31, 2005 (n of
      cases = 19,043, n of controls = 19,043). AD cases, diagnosed according to NINCS
      ADRDA and the DSM-IV criteria, were identified from Special Reimbursement
      Register. Information on HT use was collected from national prescription
      register, and data on surgery and uterine/ovarian/cervical cancer were obtained
      from the hospital discharge register. Most of the women (91.8%) were over 51
      years of age when the surgery was performed. RESULTS: Oophorectomy, hysterectomy,
      and hysterectomy with bilateral oophorectomy were associated with lower risk of
      AD (OR/95% CI: 0.85/0.75-0.97, 0.89/0.81-0.97 and 0.85/0.75-0.98, respectively)
      among women without the history of uterine/ovarian/cervical cancer, although the
      absolute risk difference was small. The association was not evident in women with
      uterine/ovarian/cervical cancer history (3.00/0.20-44.87 for all surgeries). The
      associations were not modified by HT use, which was independently associated with
      AD risk, with longer use showing protective association. CONCLUSION: Our findings
      indicate that oophorectomy with or without hysterectomy after commencement of
      natural menopause is not an important determinant of AD risk in older age and
      support the critical window hypothesis for HT use.

PMID- 24898657
TI  - Is there more to subjective cognitive impairment than meets the eye? A
      perspective.
AB  - Multi-disciplinary research has revealed evidence of significant abnormality in a
      much wider range and level of information processing than that currently
      definitive for amnestic mild cognitive impairment (MCI). This raises the
      possibility that the contemporary approach to MCI is inappropriately delimited,
      and the true nature and extent of brain dysfunction and thus disease burden,
      underestimated. It follows therefore that the closely related concept of
      subjective cognitive impairment (SCI) may be similarly constrained. Although
      research into the wider range of potential brain dysfunction in MCI and SCI is in
      its infancy, as yet precluding systematic reviews, we present here findings to
      prompt debate about SCI with respect to its clinical assessment and its personal
      and societal burden. 

PMID- 24898658
TI  - Decreased expression of cathepsin D in monocytes is related to the defective
      degradation of amyloid-beta in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative dementia
      characterized by pathological senile plaques composed of amyloid-beta (Abeta) in
      the cerebral cortex and hippocampus. Bone marrow-derived monocytes of patients
      with AD migrate across the blood-brain barrier into the brain, but are defective
      at clearing Abeta in the neuritic plaques. However, the underlying mechanisms
      remain unclear. Here, in patients with AD, we found that cathepsin D, a major
      lysosomal aspartic protease, was underexpressed in monocytes, resulting in the
      defective degradation of Abeta by monocytes/macrophages. Further, downregulation
      of cathepsin D in THP-1 cells significantly reduced the clearance of amyloid
      plaques in the brain sections of AbetaPP/PS1 mice. The clearance ability was
      recovered by the overexpression of cathepsin D in AD monocytes. These results
      suggest that decreased expression of cathepsin D in the peripheral monocytes is a
      potential signature of AD, and that this decreased expression is involved in
      Abeta degradation and AD pathogenesis. 

PMID- 24898659
TI  - Positive association between plasma amylin and cognition in a homebound elderly
      population.
AB  - Our recent study reported that amylin, a pancreatic peptide that readily crosses
      the blood-brain barrier, improves learning and memory in Alzheimer's disease
      mouse models. However, the relationship between peripheral amylin and cognition
      in humans is unknown. In this follow-up study, using a cross-sectional, homebound
      elderly population, improvement in cognitive function with increasing quartiles
      of plasma amylin was suggested by positive association with verbal memory (p =
      0.0002) and visuoconstruction tasks (p = 0.004), and inverse association with
      timed measures of attention (p < 0.0001) and executive function (p = 0.04). After
      adjusting for demographic information, apolipoprotein E4 allele, diabetes,
      stroke, kidney function, and lipid profile, log10 of plasma amylin remained
      associated with these cognitive domains. In contrast, plasma amyloid-beta peptide
      was not associated with these specific cognitive domains. Our study suggests that
      peripheral amylin may be protective for cognitive decline, especially in the
      domains affected by Alzheimer's disease. 

PMID- 24898661
TI  - A cell model for the initial phase of sporadic Alzheimer's disease.
AB  - Recent data suggest that the combined effect of oxidative stress due to aging and
      slightly elevated amyloid-beta (Abeta) levels initiate Alzheimer's disease (AD)
      long before the clinical onset. Investigations of this early phase are hampered
      by the lack of cellular or animal models reflecting this scenario. We used SH
      SY5Y cells stably transfected with an additional copy of the human AbetaPP gene
      and artificial aging by complex I inhibition. These cells show slightly elevated
      Abeta levels, moderately decreased ATP levels, impaired mitochondrial membrane
      potential, and decreased mitochondrial respiration. Assessing mitochondrial
      dynamics with three different methods reveals a distinct shift toward
      mitochondrial fission and fragmentation in SH-SY5Y AbetaPPwt cells. We also
      performed electron cryo-tomography of isolated mitochondria to reveal that there
      were no major differences between SH-SY5Y control and SH-SY5Y AbetaPPwt
      mitochondria with respect to swelling or loss of cristae. Dystrophic neurites are
      an early pathological feature of AD. Interestingly, SH-SY5Y AbetaPPwt cells
      exhibit significantly longer neurites, likely due to substantially elevated
      levels of sAbetaPPalpha. Complex I inhibition also shows substantial effects on
      mitochondrial dynamics, impairs neuritogenesis, and elevates Abeta levels in both
      cell types. In SH-SY5Y AbetaPPwt cells, these defects were more pronounced due to
      a relatively elevated Abeta and a reduced sAbetaPPalpha production. Our findings
      suggest that the progression from low Abeta levels to the beginning of AD takes
      place in the presence of oxidative stress during normal aging. This mechanism not
      only results from additive effects of both mechanisms on mitochondrial function
      but might also be additionally aggravated by altered amyloidogenic processing. 

PMID- 24898662
TI  - A DFT and ONIOM study of C-H hydroxylation catalyzed by nitrobenzene 1,2
      dioxygenase.
AB  - A detailed description of the mechanism of C-H hydroxylation by Rieske non-heme
      iron dioxygenases remains elusive, as the nature of the oxidizing species is not
      definitively known. DFT calculations on cluster models of nitrobenzene 1,2
      dioxygenase were done to explore possible mechanisms arising from oxidation by
      either the experimentally observed Fe(III)-OOH complex or the putative high
      valent HO-Fe(V)=O intermediate formed through a heterolytic O-O bond cleavage.
      Hydrogen abstraction by HO-Fe(V)=O, followed by oxygen rebound, was found to be
      consistent with experimental studies. The findings from the quantum mechanical
      cluster approach were verified by accounting for the effect of the protein
      environment on transition state geometries and reaction barriers through ONIOM
      calculations.

PMID- 24898663
TI  - The solution structure of bis(phenazine-1-carboxamide)-DNA complexes: MLN 944
      binding corrected and extended.
AB  - MLN 944 is a bisintercalating DNA-binding antitumor agent known to be a template
      inhibitor of transcription. Previous (1) H NMR studies of its d(ATGCAT)2 complex
      concluded that its phenazine chromophores are protonated. However, we find that
      this is not so, which has important consequences for the charged state of the
      ligand, for the orientation of its 1-carboxamide group in the complex, and for
      the details of the interaction of its protonated interchromophore linker with the
      DNA base pairs. Here, we report a corrected solution structure of the MLN 944
      d(ATGCAT)2 complex, and extend the study to complexes with d(TATGCATA)2 , and
      d(TACGCGTA)2 , using a variety of (1) H and (31) P NMR methods and molecular
      dynamics simulations employing the AMBER 12 force field. We find that for all
      three complexes MLN 944 binds as a dication, in which the chromophores are
      uncharged, in the DNA major groove spanning the central 2 GC base pairs in a
      manner that maintains the dyad symmetry of the DNA. The carboxamide group lies in
      the plane of the chromophore, its NH making hydrogen bonding interactions with
      the phenazine N10 nitrogen, and the protonated linkers form hydrogen bonds with
      the O6 atom of guanine. The dynamics simulations reveal extensive solvent
      interactions involving the linker amines, the carboxamide group, and the DNA
      bases.

PMID- 24898664
TI  - The significance of single nucleotide polymorphism rs2070770 in CD20 gene in
      Chinese patients with diffuse large B-cell lymphoma.
AB  - The purpose of this study was to investigate the significance of polymorphisms in
      the CD20 gene in patients with diffuse large B-cell lymphoma (DLBCL). We
      sequenced exons 3-8 in 160 patients with de novo DLBCL and detected the
      expression of CD20 via immunohistochemistry. We found two single nucleotide
      polymorphisms (SNPs): rs17155019 in the 5' untranslated region and rs2070770
      (ILE72/ILE72) in exon 4. There was no significant difference in genotype
      frequencies of SNPs between patients and controls (p = 0.855 and 0.251,
      respectively). In patients who received rituximab-containing chemotherapies, the
      T allele of rs2070770 was significantly associated with superior overall survival
      (OS) (p = 0.029) and progression-free survival (p = 0.045). Analogously, in
      patients who did not receive rituximab, the T allele of rs2070770 (p = 0.047) was
      also significantly associated with longer OS. In conclusion, SNPs of CD20 were
      not high risk factors of DLBCL, but the T allele of rs2070770 was a potential
      indicator of superior survival. 

PMID- 24898660
TI  - Small molecule p75NTR ligands reduce pathological phosphorylation and misfolding
      of tau, inflammatory changes, cholinergic degeneration, and cognitive deficits in
      AbetaPP(L/S) transgenic mice.
AB  - The p75 neurotrophin receptor (p75NTR) is involved in degenerative mechanisms
      related to Alzheimer's disease (AD). In addition, p75NTR levels are increased in
      AD and the receptor is expressed by neurons that are particularly vulnerable in
      the disease. Therefore, modulating p75NTR function may be a significant disease
      modifying treatment approach. Prior studies indicated that the non-peptide, small
      molecule p75NTR ligands LM11A-31, and chemically unrelated LM11A-24, could block
      amyloid-beta-induced deleterious signaling and neurodegeneration in vitro, and
      LM11A-31 was found to mitigate neuritic degeneration and behavioral deficits in a
      mouse model of AD. In this study, we determined whether these in vivo findings
      represent class effects of p75NTR ligands by examining LM11A-24 effects. In
      addition, the range of compound effects was further examined by evaluating tau
      pathology and neuroinflammation. Following oral administration, both ligands
      reached brain concentrations known to provide neuroprotection in vitro. Compound
      induction of p75NTR cleavage provided evidence for CNS target engagement. LM11A
      31 and LM11A-24 reduced excessive phosphorylation of tau, and LM11A-31 also
      inhibited its aberrant folding. Both ligands decreased activation of microglia,
      while LM11A-31 attenuated reactive astrocytes. Along with decreased inflammatory
      responses, both ligands reduced cholinergic neurite degeneration. In addition to
      the amelioration of neuropathology in AD model mice, LM11A-31, but not LM11A-24,
      prevented impairments in water maze performance, while both ligands prevented
      deficits in fear conditioning. These findings support a role for p75NTR ligands
      in preventing fundamental tau-related pathologic mechanisms in AD, and further
      validate the development of these small molecules as a new class of therapeutic
      compounds. 

PMID- 24898665
TI  - Patients with relapsed follicular lymphoma treated with rituximab versus
      tositumomab and iodine I-131 tositumomab.

PMID- 24898666
TI  - Src family kinases and their role in hematological malignancies.
AB  - The Src family protein tyrosine kinases (SFKs) are non-receptor intracellular
      kinases that have important roles in both hematopoiesis and leukemogenesis. The
      derangement of their expression or activation has been demonstrated to contribute
      to hematological malignancies. This review first examines the mechanisms of SFK
      overexpression and hyperactivation, emphasizing the dysregulation of the upstream
      modulators. Subsequently, the role of SFK up-regulation in the initiation,
      progression and therapy resistance of many hematological malignancies is also
      analyzed. The presented evidence endeavors to highlight the influence of SFK up
      regulation on an extensive number of hematological malignancies and the need to
      consider them as candidates in targeted anticancer therapy. 

PMID- 24898667
TI  - Is there a role for omacetaxine in the management of chronic myelogenous leukemia
      in the era of the tyrosine kinase inhibitors?

PMID- 24898668
TI  - Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage.
AB  - The tumor suppressor p53 is often mutated in human cancers. Restoring its
      antitumor activity has been shown to be a promising therapeutic approach for
      cancer treatment. Here we analyzed the activity and mechanism of a p53
      reactivator, ellipticine, in a cellular model of cutaneous T-cell lymphoma
      (CTCL), a disease that is progressive, chemoresistant and refractory to
      treatment. We tested the effect of ellipticine in three cell lines with different
      p53 status: MyLa2000 (p53(wt/wt)), SeAx ((G245S)p53) and Hut-78 ((R196Stop)p53).
      Ellipticine caused apoptosis in MyLa2000 and SeAx and restored the
      transcriptional activity of (G245S)p53 in SeAx. However, p53 siRNA knockdown
      experiments revealed that p53 was not required for ellipticine-induced apoptosis
      in CTCL. The lipophilic antioxidant alpha-tocopherol inhibited ellipticine
      dependent apoptosis and we linked the apoptotic response to the oxidative DNA
      damage. Our results provide evidence that ellipticine-induced apoptosis is
      exerted through DNA damage and does not require p53 activation in T-cell
      lymphoma. 

PMID- 24898669
TI  - New anti-CD20 monoclonal antibodies: which is the best?

PMID- 24898670
TI  - Sensitization enhancement of europium in ZnSe/ZnS core/shell quantum dots induced
      by efficient energy transfer.
AB  - Eu-doped ZnSe:/ZnS quantum dots (formed as ZnSe:Eu/ZnS QDs) were successfully
      synthesized by a two-step wet chemical method: nucleation doping and epitaxial
      shell growing. The sensitization characteristics of Eu-doped ZnSe and ZnSe/ZnS
      core/shell QD are studied in detail using photoluminescence (PL), PL excitation
      spectra (PLE) and time-resolved PL spectroscopy. The emission intensity of Eu
      ions is enhanced and that of ZnSe QDs is decreased, implying that energy was
      transferred from the excited ZnSe host materials (the donor) to the doped Eu ions
      (the acceptor). PLE reveals that the ZnSe QDs act as an antenna for the
      sensitization of Eu ions through an energy transfer process. The dynamics of
      ZnSe:Eu/ZnS core/shell quantum dots with different shell thicknesses and doping
      concentrations are studied via PL spectra and fluorescence lifetime spectra. The
      maximum phosphorescence efficiency is obtained when the doping concentration of
      Eu is approximately 6% and the sample showed strong white light under ultraviolet
      lamp illumination. By surface modification with ZnS shell layer, the intensity of
      Eu-related PL emission is increased approximately three times compared with that
      of pure ZnSe:Eu QDs. The emission intensity and wavelength of ZnSe:Eu/ZnS
      core/shell quantum dots can be modulated by different shell thickness and doping
      concentration. The results provide a valuable insight into the doping control for
      practical applications in laser, light-emitting diodes and in the field of
      biotechnology.

PMID- 24898671
TI  - Contrasting levels of connectivity and localised persistence characterise the
      latitudinal distribution of a wind-dispersed rainforest canopy tree.
AB  - Contrasting signals of genetic divergence due to historic and contemporary gene
      flow were inferred for Coachwood, Ceratopetalum apetalum (Cunoniaceae), a wind
      dispersed canopy tree endemic to eastern Australian warm temperate rainforest.
      Analysis of nine nuclear microsatellites across 22 localities revealed two
      clusters between northern and southern regions and with vicariance centred on the
      wide Hunter River Valley. Within populations diversity was high indicating a
      relatively high level of pollen dispersal among populations. Genetic variation
      was correlated to differences in regional biogeography and ecology corresponding
      to IBRA regions, primary factors being soil type and rainfall. Eleven haplotypes
      were identified by chloroplast microsatellite analysis from the same 22
      localities. A lack of chloroplast diversity within sites demonstrates limited
      gene flow via seed dispersal. Network representation indicated regional sharing
      of haplotypes indicative of multiple Pleistocene refugia as well as deep
      divergences between regional elements of present populations. Chloroplast
      differentiation between sites in the upper and lower sections of the northern
      population is reflective of historic vicariance at the Clarence River Corridor.
      There was no simple vicariance explanation for the distribution of the divergent
      southern chlorotype, but its distribution may be explained by the effects of
      drift from a larger initial gene pool. Both the Hunter and Clarence River Valleys
      represent significant dry breaks within the species range, consistent with this
      species being rainfall dependent rather than cold-adapted.

PMID- 24898673
TI  - Hydroalumination of a chlorotrialkynylsilane: spontaneous stepwise 1,3-dyotropic
      rearrangement via an intermediate silyl cation.
AB  - A new functionalised alkynylsilane, Cl-Si(C?C-CMe3 )3 (3), was obtained by a
      facile multistep synthesis. Treatment of 3 with equimolar quantities of the
      hydrides H-M(CMe3 )2 (M=Al, Ga) gave the mixed alkenyl-di(alkynyl)silanes, in
      which the chlorine atom adopts a bridging position between the aluminium and
      silicon atoms. Dual hydrogallation of 3 resulted in the formation of a
      di(alkenyl)-alkynylsilane containing two gallium atoms, one of which is
      coordinated to the chlorine atom, and the second is bonded to the alpha-carbon
      atom of the remaining alkynyl group. A tert-butylsilane was unexpectedly formed
      by a unique 1,3-dyotropic chlorine-tert-butyl exchange for the corresponding
      dialuminium compound. One aluminium atom is bonded to a tert-butyl group, a
      terminal chlorine atom and the alpha-carbon atom of the ethynyl moiety; the
      second is coordinatively unsaturated, with two terminal tert-butyl substituents.
      High-level quantum-chemical calculations favour a stepwise dyotropic
      rearrangement with an intermediate cationic silicon species over a simultaneous
      tert-butyl-chlorine migration via a five-coordinate silicon atom in the
      transition state. 

PMID- 24898674
TI  - Secondary gastrectomy for stage IV gastroesophageal adenocarcinoma after
      induction-chemotherapy.
AB  - PURPOSE: With improved chemotherapeutic regimens, metastasized gastric cancer may
      show a good response rendering an initially unresectable tumor resectable. We
      performed a retrospective analysis on the outcome of stage IV gastric cancer
      patients treated by chemotherapy followed by oncologic resection in a western
      institution. METHODS: From August 1988 to December 2010, a total number of 1,817
      patients underwent surgery for gastric cancer at the Department of Surgery,
      Technical University of Munich. A retrospective analysis of our prospective
      gastric cancer database identified 58 patients with stage IV gastric cancer
      having undergone induction chemotherapy followed by surgery in an individualized
      treatment concept. After induction chemotherapy usually consisting of 2 cycles of
      PLF (cisplatin, 5-fluorouracil, leucovorin), resection was performed with or
      without removal of metastases in patients without disease progression. Patients
      were followed up until death or loss to follow up. RESULTS: The three most common
      metastatic locations were liver (27.6 %), distant lymph nodes (22.4 %), and
      peritoneum (19.0 %). Of patients, 13.8 % had metastases in more than one
      location. Thirty-day mortality was 5.2 %, 90-day mortality was 13.8 %, while
      overall postoperative morbidity accounted for 24 %. In 19 (32.8 %) patients, a
      complete resection without any macroscopic tumor residues was achieved. In 39
      (67.2 %) patients, tumors could not be completely removed with either local
      residual disease or residual disease at distant sites. Overall median survival
      was 20 months, while patients without residual tumor survived significantly
      longer (72 months) than patients with residual disease (12 months, p = 0.001).
      CONCLUSION: Secondary surgery of metastasized gastric cancer may be justified in
      selected cases without progression under induction chemotherapy. An achievable
      complete removal of the primary tumor and metastases appears the main selection
      criterion for patients benefitting from this approach.

PMID- 24898672
TI  - Management of the lymph node-positive neck in the patient with human
      papillomavirus-associated oropharyngeal cancer.
AB  - BACKGROUND: The goal of the current study was to assess the rates of recurrence
      in the neck for patients with lymph node-positive human papillomavirus-associated
      cancer of the oropharynx who were treated with definitive radiotherapy (with or
      without chemotherapy). METHODS: This is a single-institution retrospective study.
      Methodology included database search, and statistical testing including frequency
      analysis, Kaplan-Meier tests, and comparative tests including chi-square,
      logistic regression, and log-rank. RESULTS: The cohort consisted of 401 patients
      with lymph node-positive disease who underwent radiotherapy between January 2006
      and June 2012. A total of 388 patients had computed tomography restaging, and 251
      had positron emission tomography and/or ultrasound as a component of their
      postradiation staging. Eighty patients (20%) underwent neck dissection, and 21
      patients (26%) had a positive specimen. The rate of neck dissection increased
      with increasing lymph node stage, and was lower in patients who had positron
      emission tomography scans or ultrasound in addition to computed tomography
      restaging. The median follow-up was 30 months. The 2-year actuarial neck
      recurrence rate was 7% and 5%, respectively, in all patients and those with local
      control. Lymph node recurrence rates were greater in current smokers (P = .008).
      There was no difference in lymph node recurrence rates noted between patients who
      did and those who did not undergo a neck dissection (P = .4) CONCLUSIONS: A
      treatment strategy of (chemo)radiation with neck dissection performed based on
      response resulted in high rates of regional disease control in patients with
      human papillomavirus-associated oropharyngeal cancer.

PMID- 24898675
TI  - Atopic dermatitis, STAT3- and DOCK8-hyper-IgE syndromes differ in IgE-based
      sensitization pattern.
AB  - BACKGROUND: Increased serum IgE levels are characteristic but not specific for
      allergic diseases. Particularly, severe atopic dermatitis (AD) overlaps with
      hyper-IgE syndromes (HIES) regarding eczema, eosinophilia, and increased serum
      IgE levels. HIES are primary immunodeficiencies due to monogenetic defects such
      as in the genes DOCK8 and STAT3. As it is not known to date why allergic
      manifestations are not present in all HIES entities, we assessed the specificity
      of serum IgE of AD and HIES patients in the context of clinical and immunological
      findings. METHODS: Clinical data, skin prick tests, specific IgE to aero- and
      food allergens, and T helper (Th) subpopulations were compared in AD and
      molecularly defined HIES patients. RESULTS: Total serum IgE levels were similarly
      increased in STAT3-HIES, DOCK8-HIES, and AD patients. The ratio of aeroallergen
      specific IgE to total IgE was highest in AD, whereas DOCK8-HIES patients showed
      the highest specific serum IgE against food allergens. Overall, clinical allergy
      and skin prick test results complied with the specific IgE results. Th2-cell
      numbers were significantly increased in DOCK8-HIES and AD patients compared to
      STAT3-HIES patients and controls. AD patients showed significantly higher nTreg
      cell counts compared to STAT3-HIES and control individuals. High Th17-cell counts
      were associated with asthma. Specific IgE values, skin prick test, and T-cell
      subsets of STAT3-HIES patients were comparable with those of healthy individuals
      except decreased Th17-cell counts. CONCLUSION: Hyper-IgE syndromes and atopic
      dermatitis patients showed different sensitization pattern of serum IgE
      corresponding to the allergic disease manifestations and Th-cell subset data,
      suggesting a key role of DOCK8 in the development of food allergy.

PMID- 24898676
TI  - The accuracy of allergometric test for diagnosis of food allergy.

PMID- 24898677
TI  - Primary prevention of food allergy in children and adults.

PMID- 24898678
TI  - Methods report on the development of the 2013 revision and update of the
      EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis,
      and management of urticaria.
AB  - This methods report describes the process of guideline development in detail. It
      is the result of a systematic literature review using the 'Grading of
      Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a
      structured consensus conference held on 28 and 29 November 2012, in Berlin. It is
      a joint initiative of the Dermatology Section of the European Academy of Allergy
      and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global
      Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum
      (EDF), and the World Allergy Organization (WAO) with the participation of
      delegates of 21 national and international societies. This guideline covers the
      definition and classification of urticaria, taking into account the recent
      progress in identifying its causes, eliciting factors and pathomechanisms. In
      addition, it outlines evidence-based diagnostic and therapeutic approaches for
      the different subtypes of urticaria. This guideline was acknowledged and accepted
      by the European Union of Medical Specialists (UEMS) and is published in Allergy
      2014; 69:868-887. 

PMID- 24898679
TI  - Inflammation and peripheral venous disease. The San Diego Population Study.
AB  - The inflammatory response to healing in venous thrombosis might cause vein damage
      and post-thrombotic syndrome. Inflammation may also be involved in venous
      insufficiency apart from deep-vein thrombosis. We studied the association of
      inflammation markers with venous insufficiency in a general population sample. We
      characterised 2,404 men and women in a general population cohort for peripheral
      venous disease and its severity using physical exam, symptom assessment, and
      venous ultrasound. Inflammation markers, C-reactive protein (CRP), fibrinogen,
      interleukin 1-beta (IL-1-beta), IL-8, IL-10, intercellular adhesion molecule-1
      (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte
      chemoattractant-1 (MCP-1) and vascular endothelial cell growth factor (VEGF) were
      compared in 352 case participants with peripheral venous disease and 352 controls
      with no venous abnormalities frequency matched to cases by age, sex and race.
      Associations were also evaluated including a subset of 108 cases of severe venous
      disease, as previously defined. Odds ratios (95% CI), for peripheral venous
      disease for biomarkers in the top quartile (adjusting for age, race, sex, body
      mass index and history of venous thrombosis) were 1.8 (1.1-3.0), 1.6 (1.0-2.5)
      and 1.5 (0.9-2.3) for CRP, fibrinogen and IL-10, respectively. Associations were
      larger considering cases of severe venous disease, with odds ratios for these
      three analytes of 2.6 (1.2-5.9), 3.1 (1.3-7.3) and 2.2 (1.1-4.4), and for IL-8:
      2.4 (1.1-5.2). There was no association of IL-1-beta, ICAM-1, VCAM-1, E-selectin,
      MCP-1 or VEGF with overall cases or severe venous disease. In conclusion, a
      subset of inflammation markers were associated with increased risk of peripheral
      venous disease, suggesting potential therapeutic targets for treatment. 

PMID- 24898680
TI  - Perioperative rehabilitation in operation for lung cancer (PROLUCA) - rationale
      and design.
AB  - BACKGROUND: The purpose of the PROLUCA study is to investigate the efficacy of
      preoperative and early postoperative rehabilitation in a non-hospital setting in
      patients with operable lung cancer with special focus on exercise. METHODS: Using
      a 2 x 2 factorial design with continuous effect endpoint (Maximal Oxygen Uptake
      (VO2peak)), 380 patients with non-small cell lung cancer (NSCLC) stage I-IIIa
      referred for surgical resection will be randomly assigned to one of four groups:
      (1) preoperative and early postoperative rehabilitation (starting two weeks after
      surgery); (2) preoperative and late postoperative rehabilitation (starting six
      weeks after surgery); (3) early postoperative rehabilitation alone; (4) today's
      standard care which is postoperative rehabilitation initiated six weeks after
      surgery. The preoperative rehabilitation program consists of an individually
      designed, 30-minute home-based exercise program performed daily. The
      postoperative rehabilitation program consists of a supervised group exercise
      program comprising cardiovascular and resistance training two-hour weekly for 12
      weeks combined with individual counseling. The primary study endpoint is VO2peak
      and secondary endpoints include: Six-minute walk distance (6MWD), one-repetition
      maximum (1RM), pulmonary function, patient-reported outcomes (PROs) on health
      related quality of life (HRQoL), symptoms and side effects of the cancer disease
      and the treatment of the disease, anxiety, depression, wellbeing, lifestyle,
      hospitalization time, sick leave, work status, postoperative complications (up to
      30 days after surgery) and survival. Endpoints will be assessed at baseline, the
      day before surgery, pre-intervention, post-intervention, six months after surgery
      and one year after surgery. DISCUSSION: The results of the PROLUCA study may
      potentially contribute to the identification of the optimal perioperative
      rehabilitation for operable lung cancer patients focusing on exercise initiated
      immediately after diagnosis and rehabilitation shortly after surgery. TRIAL
      REGISTRATION: NCT01893580.

PMID- 24898681
TI  - Factors affecting sperm fertilizing capacity in men infected with HIV.
AB  - Studies on the sperm-fertilizing capacity of HIV-seropositive men show
      conflicting results for reasons that are not yet clear. The aim of this study was
      to investigate the effects and relationships of some factors such as patient age,
      CD4(+) cells count, fathering offspring, concomitant sexually transmitted
      diseases (STD), and receipt of highly active anti-retroviral therapy (HAART) on
      sperm fertilizing capacity. Semen samples were collected from 33 HIV-seropositive
      men. Data on the above factors were acquired from a self-designed questionnaire.
      Computer-assisted sperm analysis, a hypo-osmotic swelling, and zona-free hamster
      oocyte penetration tests were performed according to criteria of the World Health
      Organization. CD4(+) cells in peripheral blood were examined using a flow
      cytometric (FCM) analyzer. Sperm vitality, sperm motility (grades a + b), total
      sperm motility, and sperm penetration rates were significantly higher in patients
      whose CD4(+) counts were ?350/ul than in those whose CD4(+) counts were <350/ul
      (P < 0.05), and the parameters mentioned above were also significantly correlated
      with CD4(+) cell number (all P < 0.05). Significant differences in total sperm
      count and sperm tail swelling rate between patients co-infected with STD and
      without STD were observed (P < 0.05). Sperm penetration rate in patients
      receiving HAART was significantly higher than in those not receiving HAART (P <
      0.05). Blood CD4(+) cell counts are an important indicator for evaluating sperm
      fertilizing capacity of HIV-seropositive men. After receiving HAART, the sperm
      penetration rate of HIV-seropositive men can be improved.

PMID- 24898682
TI  - Single-shot three-dimensional structure determination of nanocrystals with
      femtosecond X-ray free-electron laser pulses.
AB  - Conventional three-dimensional (3D) structure determination methods require
      either multiple measurements at different sample orientations or a collection of
      serial sections through a sample. Here we report the experimental demonstration
      of single-shot 3D structure determination of an object; in this case, individual
      gold nanocrystals at ~5.5 nm resolution using ~10 fs X-ray free-electron laser
      pulses. Coherent diffraction patterns are collected from high-index-faceted
      nanocrystals, each struck by an X-ray free-electron laser pulse. Taking advantage
      of the symmetry of the nanocrystal and the curvature of the Ewald sphere, we
      reconstruct the 3D structure of each nanocrystal from a single-shot diffraction
      pattern. By averaging a sufficient number of identical nanocrystals, this method
      may be used to determine the 3D structure of nanocrystals at atomic resolution.
      As symmetry exists in many virus particles, this method may also be applied to 3D
      structure studies of such particles at nanometer resolution on femtosecond time
      scales.

PMID- 24898683
TI  - Reproducibility of a quantitative cutaneous cytological technique.
AB  - BACKGROUND: Cutaneous cytology is a valuable tool for diagnosis of canine
      superficial pyoderma. Current published reproducible techniques are
      semiquantitative. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate
      the reproducibility of a quantitative method for skin surface cytology in dogs
      with superficial pyoderma. ANIMALS: Impression smears were collected from five
      normal dogs and 20 dogs with clinical and cytological evidence of superficial
      pyoderma. METHODS: Four investigators evaluated 10 oil immersion fields (OIF) on
      25 slides, selecting fields with inflammatory cells, nuclear streaming and or
      keratinocytes under *10 magnification. Investigators repeated blinded evaluations
      of all slides at least twice. For each OIF, polymorphonuclear leukocytes (PMNs),
      intracellular (IC) cocci, extracellular (EC) cocci, IC rods, EC rods and yeast
      were quantified. Nuclear streaming was scored as present or absent. For each
      parameter, within-reader and between-reader agreements were expressed by the
      intraclass correlation (ICC) value (<=0.20 poor, 0.21-0.40 fair, 0.41-0.60
      moderate, 0.61-0.80 good and 0.81-1.00 excellent) or kappa statistic (kappa).
      RESULTS: Reproducible parameters included: PMNs (ICC = 0.58), nuclear streaming
      (ICC = 0.68), EC cocci (ICC = 0.64) and IC cocci (ICC = 0.32). When qualified as
      present or absent, within-reader kappa for IC cocci was 0.71. The method
      demonstrated 93% sensitivity in identifying dogs with superficial pyoderma and
      51% specificity in identifying normal dogs according to established criteria.
      However, if criteria for normal dogs were limited to the absence of PMNs and IC
      bacteria, sensitivity of 64% and specificity of 98% were demonstrated.
      CONCLUSIONS AND CLINICAL IMPORTANCE: For several parameters, including PMNs,
      nuclear streaming, EC cocci and IC cocci, a reproducible, quantitative
      cytological technique was identified.

PMID- 24898684
TI  - Microbial bioproducts from cheese whey through fermentation with wastewater
      sludge Clostridium isolates.
AB  - We demonstrated the production of hydrogen, ethanol, and a variety of acids by
      several Clostridium species using cheese whey as substrate. These species were
      isolated from the anaerobic sediments of a municipal wastewater stabilization
      pond. Eight isolates were obtained and all were classified taxonomically as
      Clostridium spp. based on 16S rRNA sequencing. Sludge isolates showed maximum
      bioproduct production yields and productivities after approximately 24 h of batch
      cultivation with 6% (m/v) cheese whey. Fermentation byproducts measured included
      hydrogen, ethanol, acetic acid, butyric acid, and lactic acid. The maximum yields
      of bioproducts were 0.59 mol H(2)/mol lactose, 0.071 g ethanol/g, 0.204 g acetic
      acid/g, 0.218 g butyric acid/g, and 0.144 g lactic acid/g. The production of
      these high value biofuels and biofuel intermediates from cheese whey could have
      significant implications for conversion of waste to high value bioproducts to
      enhance domestic energy economies.

PMID- 24898685
TI  - Squamous cell carcinomas in situ arising in seborrheic keratoses: an association
      with concomitant immunosuppression?
AB  - BACKGROUND: Seborrheic keratoses (SK) are the most common cutaneous neoplasm in
      humans. Given their numbers, a squamous cell carcinoma in situ (SCCIS) arising
      from an SK would not be unexpected, although this occurrence has not been widely
      reported. OBJECTIVE: This study compares the immune status of patients with a
      SCCIS arising contiguously from SK (SK/SCCIS) and the number of daily medications
      taken by these patients. The biopsy tissue was evaluated for the presence of
      human papillomavirus DNA. METHODS: Over a 5-year period at our institution, 13
      cases of SK/SCCIS were diagnosed. For each case, age- and sex-matched control
      patients with a histologically diagnosed unremarkable SK were randomly selected.
      The number of patients taking immunosuppressing medications was determined from
      each group and compared statistically. In addition, polymerase chain reaction
      analysis of the 13 SK/SCCIS biopsies was performed. RESULTS: Five of the 13 study
      patients took immunosuppressive medications compared to none of the 39 control
      patients (P = 0.0005). None of the biopsies demonstrated the presence of human
      papillomavirus DNA by polymerase chain reaction. CONCLUSIONS: Immunocompromised
      patients with SKs appear to carry a greater risk of these otherwise innocuous
      lesions developing an SCCIS, although given the small number of patients
      evaluated, further research into this possible association is warranted.

PMID- 24898686
TI  - Circumscribed plantar hypokeratosis.

PMID- 24898688
TI  - Polarization-dependent enhanced photoluminescence and polarization-independent
      emission rate of quantum dots on gold elliptical nanodisc arrays.
AB  - We have fabricated gold (Au) elliptical nanodisc (ND) arrays via three-beam
      interference lithography and electron beam deposition of gold. The enhanced
      photoluminescence intensity and emission rate of quantum dots (QDs) near to the
      Au elliptical NDs have been studied by tuning the nearest distance between
      quantum dots and Au elliptical NDs. We found that the photoluminescence intensity
      is polarization-dependent with the degree of polarization being equal to that of
      the light extinction of the Au elliptical NDs, while the emission rate is
      polarization-independent. This is resulted from the plasmon-coupled emission via
      the coupling between the QD dipole and the plasmon nano-antenna. Our experiments
      fully confirm the evidence of the plasmophore concept proposed recently in the
      interaction of the QDs with metal nanoparticles. 

PMID- 24898687
TI  - Prevention of inpatient hypoglycemia with a real-time informatics alert.
AB  - BACKGROUND: Severe hypoglycemia (SH), defined as a blood glucose (BG) <40 mg/dL,
      is associated with an increased risk of adverse clinical outcomes in inpatients.
      OBJECTIVE: To determine whether a predictive informatics hypoglycemia risk-alert
      supported by trained nurse responders would reduce the incidence of SH in our
      hospital. DESIGN: A 5-month prospective cohort intervention study. SETTING: Acute
      care medical floors in a tertiary care academic hospital in St. Louis, Missouri.
      PATIENTS: From 655 inpatients on designated medical floors with a BG of <90
      mg/dL, 390 were identified as high risk for hypoglycemia by the alert system.
      MEASUREMENTS: The primary outcome was the incidence of SH occurring in high-risk
      intervention versus high-risk control patients. Secondary outcomes included:
      number of episodes of SH in all study patients, incidence of BG < 60 mg/dL and
      severe hyperglycemia with a BG >299 mg/dL, length of stay, transfer to a higher
      level of care, the frequency that high-risk patient's orders were changed in
      response to the alert-intervention process, and mortality. RESULTS: The alert
      process, when augmented by nurse-physician collaboration, resulted in a
      significant decrease by 68% in the rate of SH in alerted high-risk patients
      versus nonalerted high-risk patients (3.1% vs 9.7%, P = 0.012). Rates of
      hyperglycemia were similar on intervention and control floors at 28% each. There
      was no difference in mortality, length of stay, or patients requiring transfer to
      a higher level of care. CONCLUSION: A real-time predictive informatics-generated
      alert, when supported by trained nurse responders, significantly reduced
      inpatient SH.

PMID- 24898689
TI  - Effect of halide salts on development of surface browning on fresh-cut 'Granny
      Smith' (Malus * domestica Borkh) apple slices during storage at low temperature.
AB  - BACKGROUND: The postharvest life of fresh-cut apple slices is limited by browning
      on cut surfaces. Dipping in halide salt solutions was examined for their
      inhibition of surface browning on 'Granny Smith' apple slices and the effects on
      biochemical factors associated with browning. RESULTS: Delay in browning by salts
      was greatest with chloride = phosphate > sulfate > nitrate with no difference
      between sodium, potassium and calcium ions. The effectiveness of sodium halides
      on browning was fluoride > chloride = bromide > iodide = control. Polyphenol
      oxidase (PPO) activity of tissue extracted from chloride- and fluoride-treated
      slices was not different to control but when added into the assay solution, NaF >
      NaCl both showed lower PPO activity at pH 3-5 compared to control buffer. The
      level of polyphenols in treated slices was NaF > NaCl > control. Addition of
      chlorogenic acid to slices enhanced browning but NaCl and NaF counteracted this
      effect. There was no effect of either halide salt on respiration, ethylene
      production, ion leakage, and antioxidant activity. CONCLUSION: Dipping apple
      slices in NaCl is a low cost treatment with few impediments to commercial use and
      could be a replacement for other anti-browning additives. The mode of action of
      NaCl and NaF is through decreasing PPO activity resulting in reduced oxidation of
      polyphenols.

PMID- 24898690
TI  - Comprehensive review of sleep-related sudden unexpected infant deaths and their
      investigations: Florida 2008.
AB  - To describe 2008 Florida sleep-related sudden unexpected infant deaths (SUIDs) by
      describing (a) percentage distribution of medical examiner (ME) cause-of-death
      determinations; (b) mortality rates by maternal and infant characteristics; (c)
      prevalence of selected suffocation or sudden infant death syndrome (SIDS) risk
      and protective factors; (d) frequency of selected scene investigation and autopsy
      components (including extent of missing data); and (e) percentage with public
      health program contact. In this population-based study, we identified sleep
      related SUIDs occurring among Florida residents from the 2008-linked Florida
      infant death and birth certificates. Information about the circumstances of death
      was abstracted from ME, law enforcement, and hospital records. We used
      frequencies and percentages to describe characteristics of sleep-related SUID
      cases. Of 215 sleep-related SUID cases, MEs identified 47.9% as accidental
      suffocation and strangulation in bed, 35.4% as unknown or undetermined cause, and
      16.7% as SIDS. Sleep-related SUID most frequently occurred in an adult bed (n =
      108; 50.2%). At death, 82.4% of sleep-related SUIDs had >=1 suffocation or SIDS
      risk factor with 54.4% infants sharing a sleep surface, 38.1% placed nonsupine,
      24.2% placed on a pillow, and 10.2% having head covering. Missing data frequently
      resulted from incomplete scene investigation and autopsy components. SUID
      contributed to >=1 in seven Florida infant deaths in 2008. Approximately 80% of
      sleep-related SUIDs were reported among infants placed in unsafe sleeping
      environments. Effective interventions are needed to promote safe sleep among
      caregivers of Florida infants. These interventions must reach infant caregivers
      at highest risk and change unsafe sleep practices. The substantial percentage of
      missing investigation data reinforces the need for standardized reporting.

PMID- 24898691
TI  - The relationship between race, inflammation and psychosocial factors among
      pregnant women.
AB  - African American women have higher rates of preterm birth (PTB) than women from
      other racial or ethnic backgrounds. We explored the possibility that African
      American women experience higher anxiety/lower optimism levels, leading to excess
      inflammation, a possible pathway leading to PTB. In a cohort of 434 nulliparous
      women (African American, n = 119; Caucasian, n = 315), standardized measures of
      anxiety and optimism were completed at 20 weeks' gestation. C-reactive protein
      (CRP) was measured in serum collected at the same time, and interleukin-6 (IL-6)
      was additionally measured in African American women. African American women
      tended to have higher rates of anxiety (>75th percentile) compared to Caucasian
      women (27.3 vs. 19.2%, p = 0.08), but rates of low optimism (<25th percentile)
      did not vary by race. Contrary to our hypothesis, higher concentrations of CRP
      among African American women were associated with lower risk of anxiety in the
      highest quartile, adjusted for covariates (OR 0.65, 95% CI 0.44, 0.98). Low
      optimism in African American women was also associated with lower IL-6, but
      results were only marginally significant (OR 0.43, 95% CI 0.17, 1.10). CRP,
      anxiety, and optimism were not correlated among Caucasian women. African American
      women with high anxiety or low optimism had lower concentrations of pro
      inflammatory markers at mid-gestation compared to those without these
      characteristics. Our results suggest that chronic anxiety among African American
      women may contribute to intractable race disparities in pregnancy outcomes via an
      impaired inflammatory response.

PMID- 24898693
TI  - Medication complexity and affordability in use of time release antidepressants.
AB  - While time-release (TR) formulations reduce medication complexity, their
      increased costs may compromise medication affordability. This study examined how
      medication complexity and affordability affect the extent of access to TR
      formulations among adult patients with depression. Study subjects consisted of
      adults (>= 24 years old) with reported diagnoses of depression from the 2010
      Medical Expenditure Panel Survey (MEPS). Antidepressants that offer choices
      between TR vs. IR (immediate release) were selected. Factors related to
      medication complexity and affordability were identifi ed based on the Anderson?fs
      model of health services utilization. A multivariate logistic regression was used
      to examine the study hypotheses while controlling for complex survey sampling in
      MEPS. A total of 625 working adults with depression had fi lled prescriptions
      with TR formulations about 60% of the time. Factors related to medication
      affordability and complexity were signifi cantly associated with the extent of
      access to TR antidepressant formulations. Identifi cation of those factors
      associated with the use of TR formulations would contribute to improving access
      as well as adherence to antidepressant drug therapy.

PMID- 24898692
TI  - ATP binding turns plant cryptochrome into an efficient natural photoswitch.
AB  - Cryptochromes are flavoproteins that drive diverse developmental light-responses
      in plants and participate in the circadian clock in animals. Plant cryptochromes
      have found application as photoswitches in optogenetics. We have studied effects
      of pH and ATP on the functionally relevant photoreduction of the oxidized FAD
      cofactor to the semi-reduced FADH(.) radical in isolated Arabidopsis cryptochrome
      1 by transient absorption spectroscopy on nanosecond to millisecond timescales.
      In the absence of ATP, the yield of light-induced radicals strongly decreased
      with increasing pH from 6.5 to 8.5. With ATP present, these yields were
      significantly higher and virtually pH-independent up to pH 9. Analysis of our
      data in light of the crystallographic structure suggests that ATP-binding shifts
      the pKa of aspartic acid D396, the putative proton donor to FAD.(-), from ~7.4 to
      >9, and favours a reaction pathway yielding long-lived aspartate D396(-). Its
      negative charge could trigger conformational changes necessary for signal
      transduction. 

PMID- 24898694
TI  - Participatory eHealth development to support nurses in antimicrobial stewardship.
AB  - BACKGROUND: Antimicrobial resistance poses a threat to patient safety worldwide.
      To stop antimicrobial resistance, Antimicrobial Stewardship Programs (ASPs;
      programs for optimizing antimicrobial use), need to be implemented. Within these
      programs, nurses are important actors, as they put antimicrobial treatment into
      effect. To optimally support nurses in ASPs, they should have access to
      information that supports them in their preparation, administration and
      monitoring tasks. In addition, it should help them to detect possible risks or
      adverse events associated with antimicrobial therapy. In this formative study, we
      investigate how nurses' can be supported in ASPs by means of an eHealth
      intervention that targets their information needs. METHODS: We applied a
      participatory development approach that involves iterative cycles in which health
      care workers, mostly nurses, participate. Focus groups, observations, prototype
      evaluations (via a card sort task and a scenario-based information searching
      task) and interviews are done with stakeholders (nurses, managers, pharmacist,
      and microbiologist) on two pulmonary wards of a 1000-bed teaching hospital.
      RESULTS: To perform the complex antimicrobial-related tasks well, nurses need to
      consult various information sources on a myriad of occasions. In addition, the
      current information infrastructure is unsupportive of ASP-related tasks, mainly
      because information is not structured to match nurse tasks, is hard to find, out
      of date, and insufficiently supportive of awareness. Based our findings, we
      created a concept for a nurse information application. We attuned the
      application's functionality, content, and structure to nurse work practice and
      tasks. CONCLUSIONS: By applying a participatory development approach, we showed
      that task support is a basic need for nurses. Participatory development proved
      useful regarding several aspects. First, it allows for combining bottom-up needs
      (nurses') and top-down legislations (medical protocols). Second, it enabled us to
      fragmentise and analyse tasks and to reduce and translate extensive information
      into task-oriented content. Third, this facilitated a tailored application to
      support awareness and enhance patient safety. Finally, the involvement of
      stakeholders created commitment and ownership, and helped to weigh needs from
      multiple perspectives.

PMID- 24898695
TI  - Adverse cardiovascular outcomes in relation to suboptimal antithrombotic therapy
      use in patients undergoing peripheral artery disease angioplasty: lost
      opportunities?
AB  - INTRODUCTION: Current guidelines recommend antithrombotic therapy with either
      aspirin or clopidogrel for all patients with peripheral arterial disease (PAD).
      Nevertheless, cardiovascular comorbidities and perceived bleeding risk complicate
      antithrombotic management of PAD patients. We studied the proportion of patients
      receiving optimal (guideline-recommended) antithrombotic therapy, and second,
      assessed the impact of suboptimal antithrombotic therapy use to long-term
      outcomes of PAD patients. METHODS: We performed a single centre retrospective
      analysis of patients with significant PAD, requiring percutaneous intervention.
      All patients coded as undergoing peripheral artery percutaneous transluminal
      angioplasty (PTA) between January 2007 and December 2011 were reviewed.
      Antithrombotic medication on discharge postprocedure was recorded. RESULTS:
      Across the study period, 473 patients were coded as having received a PTA, but
      yet only 336 (71%) had data available for review: 218 (35.2%) male, mean age 73
      +/- 11 years. Of the whole cohort, 236 (70.2%) were discharged on optimal
      (guideline-recommended) antithrombotic therapy, 30 (8.9%) were considered
      'overtreated' and 70 (20.8%) were undertreated. On multivariate analysis,
      patients with heart failure were more likely to be undertreated (OR 2.38, 95% CI:
      1.15-5.00, p = 0.02) while patient with coronary artery disease were more likely
      to be overtreated (OR 4.00, 95% CI: 1.61-10.00, p = 0.03). Undertreated patients
      had an increased risk for all-cause mortality [hazard ratio (HR) 2.96, 95% CI
      1.81-4.82: p = 0.00001] and cardiovascular mortality (HR 3.16, 95% CI: 1.49-6.68,
      p = 0.003). CONCLUSION: In this single centre cohort of patients undergoing PTA,
      suboptimal antithrombotic therapy was not uncommon and had a major impact on long
      term outcomes, resulting in increased all cause and cardiovascular mortality.

PMID- 24898696
TI  - Wnt5a promotes vasculogenic mimicry and epithelial-mesenchymal transition via
      protein kinase Calpha in epithelial ovarian cancer.
AB  - Epithelial ovarian cancer is one of the most common causes of cancer-related
      death in women. The majority of epithelial ovarian cancer patients present with
      metastasis at the time of initial diagnosis. Studies have demonstrated that
      vasculogenic mimicry (VM) is highly correlated with metastasis and invasiveness,
      and epithelial-mesenchymal transition (EMT) is pivotal in VM formation. Wnt5a, a
      member of the Wnt protein family, can activate the non-canonical Wnt signaling
      pathway mediating cancer initiation and progression. Thus, the present study
      aimed to investigate the relationship between Wnt5a and VM and its mechanism in
      epithelial ovarian cancer. The present results showed that Wnt5a staining was
      significantly correlated with metastasis in epithelial ovarian cancer. The
      correlation between the expression of Wnt5a and VM or protein kinase Calpha
      (PKCalpha) indicated that Wnt5a was associated with VM and may be linked to the
      PKC pathway. In vitro experiments revealed that Wnt5a enhanced the vasculogenic
      capacity, motility and invasiveness of ovarian cancer cells; however, the
      PKCalpha inhibitor blocked these effects. Western blot analysis showed that
      changes in Wnt5a expression coincided with changes in PKC expression and that
      PI3K and Snail expression increased along with Wnt5a upregulation. However, no
      change was observed in beta-catenin levels, indicating that Wnt5a may mediate EMT
      and VM in ovarian cancer cells via the PKCalpha pathway.

PMID- 24898697
TI  - Characterization of a degradable polar hydrophobic ionic polyurethane with
      circulating angiogenic cells in vitro.
AB  - This study investigated the interaction of human circulating angiogenic cells
      (CACs) with a degradable polar hydrophobic ionic polyurethane (D-PHI) which has
      been previously shown to exhibit anti-inflammatory character and favorable
      interactions with human endothelial cells (ECs). Given the implication of the
      CACs in microvessel development it was of intrinsic interest to expand our
      knowledge of D-PHI biocompatibility with this relevant primary cell involved in
      angiogenesis. The findings will be compared to a well-established benchmark
      substrate for CACs, fibronectin-coated tissue culture polystyrene (TCPS).
      Immunoblotting analysis showed that CACs were a heterogeneous population of cells
      composed mostly of monocytic cells expressing the CD14 marker. Assessment of the
      cytokine release profile, using ELISA, showed that D-PHI supported a higher
      concentration of interleukin-10 (IL-10) when compared to the concentration of
      tumor necrosis factor alpha, which is indicative of an anti-inflammatory
      phenotype, and was different from the response with TCPS. It was found that the
      CACs were attached to D-PHI and remained viable and functional (nitric oxide
      production) during the seven days of culture. However, there did not appear to be
      any significant proliferation on D-PHI, contrary to the CAC growth on fibronectin
      coated TCPS. It was concluded that D-PHI displayed some of the qualities suitable
      to enable the retention of CACs onto this substrate, as well as maintaining an
      anti-inflammatory phenotype, characteristics which have been reported to be
      important for angiogenesis in vivo.

PMID- 24898699
TI  - Immunomodulatory adjuvant therapy in severe community-acquired pneumonia.
AB  - Severe pneumonia has a high mortality (38.2%) despite evidence-based therapy.
      Rising rates of antimicrobial resistance increase the urgency to develop new
      treatment strategies. Multiple adjuvant therapies for pneumonia have been
      investigated but none are currently licensed. Profound immune dysregulation
      occurs in patients with severe infection. An initial hyper-inflammatory response
      is followed by a secondary hypo-inflammatory response with 'immune-paralysis'.
      There is focus on the development of immunostimulatory agents to improve host
      ability to combat primary infection and reduce secondary infections. Successful
      treatments must be targeted to immune response; promising biomarkers exist but
      have not yet reached common bedside practice. We explore evidence for adjuvant
      therapies in community-acquired pneumonia. We highlight novel potential treatment
      strategies using a broad-based search strategy to include publications in
      pneumonia and severe sepsis. We explore reasons for the failure to develop
      effective adjuvant therapies and highlight the need for targeted therapy specific
      to immune activity. 

PMID- 24898698
TI  - Progression of intestinal permeability changes and alpha-synuclein expression in
      a mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a multifocal degenerative disorder for which there is
      no cure. The majority of cases are sporadic with unknown etiology. Recent data
      indicate that untreated patients with de novo PD have increased colonic
      permeability and that both de novo and premotor patients have pathological
      expression of alpha-synuclein (alpha-syn) in their colon. Both endpoints
      potentially can serve as disease biomarkers and even may initiate PD events
      through gut-derived, lipopolysaccharide (LPS)-induced neuronal injury. Animal
      models could be ideal for interrogating the potential role of the intestines in
      the pathogenesis of PD; however, few current animal models of PD encompass these
      nonmotor features. We sought to establish a progressive model of PD that includes
      the gastrointestinal (GI) dysfunction present in human patients. C57/BL6 mice
      were systemically administered one dose of either LPS (2.5 mg/kg) or saline and
      were sacrificed in monthly intervals (n = 5 mice for 5 months) to create a time
      course. Small and large intestinal permeability was assessed by analyzing the
      urinary output of orally ingested sugar probes through capillary column gas
      chromatography. alpha-Syn expression was assessed by counting the number of
      mildly, moderately, and severely affected myenteric ganglia neurons throughout
      the GI tract, and the counts were validated by quantitative optical density
      measurements. Nigrostriatal integrity was assessed by tyrosine hydroxylase
      immunohistochemistry stereology and densitometry. LPS caused an immediate and
      progressive increase in alpha-syn expression in the large intestine but not in
      the small intestine. Intestinal permeability of the whole gut (large and small
      intestines) progressively increased between months 2 and 4 after LPS
      administration but returned to baseline levels at month 5. Selective measurements
      demonstrated that intestinal permeability in the small intestine remained largely
      intact, suggesting that gut leakiness was predominately in the large intestine.
      Phosphorylated serine 129-alpha-syn was identified in a subset of colonic
      myenteric neurons at months 4 and 5. Although these changes were observed in the
      absence of nigrostriatal degeneration, an abrupt but insignificant increase in
      brainstem alpha-syn was observed that paralleled the restoration of permeability.
      No changes were observed over time in controls. LPS, an endotoxin used to model
      PD, causes sequential increases in alpha-syn immunoreactivity, intestinal
      permeability, and pathological alpha-syn accumulation in the colon in a manner
      similar to that observed in patients with PD. These features are observed without
      nigrostriatal degeneration and incorporate PD features before the motor syndrome.
      This allows for the potential use of this model in testing neuroprotective and
      disease-modifying therapies, including intestinal-directed therapies to fortify
      intestinal barrier integrity.

PMID- 24898700
TI  - Tumour necrosis factor-alpha promotes liver ischaemia-reperfusion injury through
      the PGC-1alpha/Mfn2 pathway.
AB  - Tumour necrosis factor (TNF)-alpha has been considered to induce ischaemia
      reperfusion injury (IRI) of liver which is characterized by energy dysmetabolism.
      Peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1alpha and
      mitofusion2 (Mfn2) are reported to be involved in the regulation of mitochondrial
      function. However, whether PGC-1alpha and Mfn2 form a pathway that mediates liver
      IRI, and if so, what the underlying involvement is in that pathway remain
      unclear. In this study, L02 cells administered recombinant human TNF-alpha had
      increased TNF-alpha levels and resulted in down-regulation of PGC-1alpha and Mfn2
      in a rat liver IRI model. This was associated with hepatic mitochondrial
      swelling, decreased adenosine triphosphate (ATP) production, and increased levels
      of reactive oxygen species (ROS) and alanine aminotransferase (ALT) activity as
      well as cell apoptosis. Inhibition of TNF-alpha by neutralizing antibody reversed
      PGC-1alpha and Mfn2 expression, and decreased hepatic injury and cell apoptosis
      both in cell culture and in animals. Treatment by rosiglitazone sustained PGC
      1alpha and Mfn2 expression both in IR livers, and L02 cells treated with TNF
      alpha as indicated by increased hepatic mitochondrial integrity and ATP
      production, reduced ROS and ALT activity as well as decreased cell apoptosis.
      Overexpression of Mfn2 by lentiviral-Mfn2 transfection decreased hepatic injury
      in IR livers and L02 cells treated with TNF-alpha. However, there was no up
      regulation of PGC-1alpha. These findings suggest that PGC-1alpha and Mfn2
      constitute a regulatory pathway, and play a critical role in TNF-alpha-induced
      hepatic IRI. Inhibition of the TNF-alpha or PGC-1alpha/Mfn2 pathways may
      represent novel therapeutic interventions for hepatic IRI. 

PMID- 24898701
TI  - Functional polymorphisms of interleukin-18 gene and risk of breast cancer in a
      Brazilian population.
AB  - Interleukin-18 (IL-18) is a key cytokine responsible for immune response and
      involved in the process of cancer development. In this case-control study, we
      tested whether IL-18 promoter polymorphism contributes to breast cancer
      susceptibility in Brazilian patients. The two groups studied were 154 patients
      with breast cancer and 118 healthy individuals. The frequency of IL-18 promoter
      single nucleotide polymorphisms (SNPs) at positions -607 (C/A) (rs1946518) and 
      137 (G/C) (rs187238) was determined by polymerase chain reaction analyses. The
      polymorphisms genotyped in this study showed a significant association with
      breast cancer under different genetic models. Both SNPs showed a positive
      association. For the IL18-607 polymorphism the best model was the codominant
      genetic model [CC vs AA, P = 0.004, odds ratio (OR) = 2.782, 95% confidence
      interval (CI) 1.385-5.589]. For IL18-137 statistical significance was found using
      the recessive genetic model (P = 0.008, OR = 3.896, 95% CI 1.427-10.639). The
      association between the haplotypes of the IL18 gene and breast cancer was further
      confirmed. Our results suggest that IL18-607 and IL18-137 polymorphism
      contributes to increase the breast cancer risk. To our knowledge, this is the
      first report regarding Brazilian breast cancer patients and IL18 promoter
      polymorphisms. 

PMID- 24898703
TI  - Photobiological characteristics of chlorophyll a derivatives as microbial PDT
      agents.
AB  - Chlorin-e6 (chl-e6) and a hydrogenated derivative (chl-e6H) were semi
      synthesized, and their photophysical properties and photodynamic activity against
      Escherichia coli, Staphylococcus aureus and Candida albicans evaluated. Methyl
      pheophorbide-a (Mepheo-a) was obtained from S. maxima using methanolic extraction
      with acid catalysis (CH3OH-H2SO4). Chlorin-e6 was prepared from Mepheo-a by basic
      hydrolysis with H2O-acetone and NaOH. Hydrogenated Chlorin-e6 was synthesized by
      a similar procedure starting from the hydrogenated methyl pheophorbide-a (Mepheo
      aH). Photophysical studies were performed in order to determine the singlet
      oxygen quantum yield of chl-e6H which is higher than that of chl-e6. The
      microorganism inactivation of chl-e6 and chl-e6H was investigated at two
      concentrations and three fluence levels. Both chl-e6 and chl-e6H showed
      microorganism inactivation against Gram-positive bacteria and a fungus.

PMID- 24898702
TI  - Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling.
AB  - BACKGROUND: Reactive oxygen species (ROS) are used by plants as signaling
      molecules during stress and development. Given the amount of possible challenges
      a plant face from their environment, plants need to activate and prioritize
      between potentially conflicting defense signaling pathways. Until recently, most
      studies on signal interactions have focused on phytohormone interaction, such as
      the antagonistic relationship between salicylic acid (SA)-jasmonic acid and
      cytokinin-auxin. RESULTS: In this study, we report an antagonistic interaction
      between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3)
      leads to a ROS burst in the apoplast and induces extensive changes in gene
      expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1
      (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1
      mutant displayed constitutive expression of defense genes and spontaneous cell
      death. To determine the exact process which blocks the apoplastic ROS signaling,
      double and triple mutants involved in various signaling pathway were generated in
      dnd1 background. Simultaneous elimination of SA-dependent and SA-independent
      signaling components from dnd1 restored its responsiveness to O3. Conversely, pre
      treatment of plants with SA or using mutants that constitutively activate SA
      signaling led to an attenuation of changes in gene expression elicited by O3.
      CONCLUSIONS: Based upon these findings, we conclude that plants are able to
      prioritize the response between ROS and SA via an antagonistic action of SA and
      SA signaling on apoplastic ROS signaling.

PMID- 24898704
TI  - Impact of rapid ventricular pacing during TAVI on microvascular tissue perfusion.
AB  - BACKGROUND: Rapid ventricular pacing (RVP) is an established technique to
      temporarily reduce left ventricular output during transcatheter aortic valve
      implantation (TAVI). The purpose of this study was to evaluate the impact of RVP
      on microvascular tissue perfusion (MTP) in patients undergoing TAVI. METHODS AND
      RESULTS: We studied 42 patients (mean age 81.8 +/- 6.9 years, n = 18 females.
      EuroSCORE 33 +/- 12 %) during TAVI. MTP was analyzed using Sidestream-Darkfield
      imaging, of the sublingual microvasculature. Microvascular flow index (MFI) was
      continuously measured in small (10-25 MUm)- and medium (26-50 MUm)-sized vessels,
      starting 10 s before and ending 12 s after RVP. Further, perfused capillary
      density, total vessel density and the proportion of perfused vessels were
      assessed. After a mean RVP duration of 14.3 s (range 6-29), mean arterial
      pressure decreased from 68 +/- 05 to 40 +/- 7 mmHg (p < 0.001). This was
      associated with a significant decrease of MFI in small- and medium-sized vessels
      from 2.29 +/- 0.64 and 2.36 +/- 0.6 to 0.87 +/- 0.66 (p < 0.001) and 1.0 +/- 0.83
      (p < 0.001), respectively. MFI remained significantly below baseline values
      (small: 1.75 +/- 0.8, p = 0.001 vs. baseline; medium: 1.77 +/- 0.85; p = 0.005
      vs. baseline) at 12 s after end of RVP. CONCLUSIONS: The study demonstrates a
      time-dependent effect of RVP on microflow, leading to 50 and 25 % of baseline at
      8 and 18 s of RVP, respectively. In a substantial proportion of patients, RVP is
      associated with microcirculatory arrest and a delayed recovery of microflow.
      Although the impact of these findings on outcome is yet unclear, TAVI operators
      should be aware of the potentially adverse effects of even short periods of RVP.

PMID- 24898706
TI  - Development and growth in synanthropic species: plasticity and constraints.
AB  - Urbanization poses serious extinction risks, yet some species thrive in urban
      environments. This may be due to a pronounced developmental plasticity in these
      taxa, since phenotypically, plastic organisms may better adjust to unpredictable
      urban food resources. We studied phenotypic plasticity in Nuctenea umbratica, a
      common European forest and urban vegetation spider. We subjected spiderlings to
      low (LF), medium (MF) and high (HF) food treatments and documented their growth
      and developmental trajectories into adulthood. Spiders from the three treatments
      had comparable numbers of instars and growth ratios, but differed in
      developmental periods. Longest developing LF spiders (? = 390, ? = 320 days) had
      the smallest adults, but MF (? = 300, ? = 240 days) and HF (? = 240, ? = 210
      days) spiders reached comparable adult sizes through shorter development. While
      males and females had comparable instar numbers, females had longer development,
      higher growth ratios, adult sizes and mass; and while males adjusted their
      moulting to food availability, female moulting depended on specific mass, not
      food treatment. We discussed the patterns of Nuctenea sex-specific development
      and compared our results with published data on two other Holarctic urban
      colonizers (Larinioides sclopetarius, Zygiella x-notata) exhibiting high
      plasticity and fast generation turn-over. We conclude that despite relatively
      unconstrained developmental time in the laboratory enabling Nuctenea to achieve
      maximal mass and size-main female fitness proxies-their relatively fixed growth
      ratio and long generation turn-over may explain their lower success in urban
      environments. 

PMID- 24898705
TI  - A process for assessing the feasibility of a network meta-analysis: a case study
      of everolimus in combination with hormonal therapy versus chemotherapy for
      advanced breast cancer.
AB  - BACKGROUND: The aim of this study is to outline a general process for assessing
      the feasibility of performing a valid network meta-analysis (NMA) of randomized
      controlled trials (RCTs) to synthesize direct and indirect evidence for
      alternative treatments for a specific disease population. METHODS: Several steps
      to assess the feasibility of an NMA are proposed based on existing
      recommendations. Next, a case study is used to illustrate this NMA feasibility
      assessment process in order to compare everolimus in combination with hormonal
      therapy to alternative chemotherapies in terms of progression-free survival for
      women with advanced breast cancer. RESULTS: A general process for assessing the
      feasibility of an NMA is outlined that incorporates explicit steps to visualize
      the heterogeneity in terms of treatment and outcome characteristics (Part A) as
      well as the study and patient characteristics (Part B). Additionally, steps are
      performed to illustrate differences within and across different types of direct
      comparisons in terms of baseline risk (Part C) and observed treatment effects
      (Part D) since there is a risk that the treatment effect modifiers identified may
      not explain the observed heterogeneity or inconsistency in the results due to
      unexpected, unreported or unmeasured differences. Depending on the data
      available, alternative approaches are suggested: list assumptions, perform a meta
      regression analysis, subgroup analysis, sensitivity analyses, or summarize why an
      NMA is not feasible. CONCLUSIONS: The process outlined to assess the feasibility
      of an NMA provides a stepwise framework that will help to ensure that the
      underlying assumptions are systematically explored and that the risks (and
      benefits) of pooling and indirectly comparing treatment effects from RCTs for a
      particular research question are transparent.

PMID- 24898707
TI  - Insight into genomic changes accompanying divergence: genetic linkage maps and
      synteny of Lucania goodei and L. parva reveal a Robertsonian fusion.
AB  - Linkage maps are important tools in evolutionary genetics and in studies of
      speciation. We performed a karyotyping study and constructed high-density linkage
      maps for two closely related killifish species, Lucania parva and L. goodei, that
      differ in salinity tolerance and still hybridize in their contact zone in
      Florida. Using SNPs from orthologous EST contigs, we compared synteny between the
      two species to determine how genomic architecture has shifted with divergence.
      Karyotyping revealed that L. goodei possesses 24 acrocentric chromosomes (1N)
      whereas L. parva possesses 23 chromosomes (1N), one of which is a large
      metacentric chromosome. Likewise, high-density single-nucleotide polymorphism
      based linkage maps indicated 24 linkage groups for L. goodei and 23 linkage
      groups for L. parva. Synteny mapping revealed two linkage groups in L. goodei
      that were highly syntenic with the largest linkage group in L. parva. Together,
      this evidence points to the largest linkage group in L. parva being the result of
      a chromosomal fusion. We further compared synteny between Lucania with the genome
      of a more distant teleost relative medaka (Oryzias latipes) and found good
      conservation of synteny at the chromosomal level. Each Lucania LG had a single
      best match with each medaka chromosome. These results provide the groundwork for
      future studies on the genetic architecture of reproductive isolation and salinity
      tolerance in Lucania and other Fundulidae.

PMID- 24898708
TI  - BZcon1, a SANT/Myb-type gene involved in the conidiation of Cochliobolus
      carbonum.
AB  - The fungal pathogen Cochliobolus carbonum (anamorph, Bipolaris zeicola) causes
      Northern Leaf Spot, leading to a ubiquitous and devastating foliar disease of
      corn in Yunnan Province, China. Asexual spores (conidia) play a major role in
      both epidemics and pathogenesis of Northern Leaf Spot, but the molecular
      mechanism of conidiation in C. carbonum has remained elusive. Here, using a map
      based cloning strategy, we cloned a single dominant gene, designated as BZcon1
      (for Bipolaris zeicola conidiation), which encodes a predicted unknown protein
      containing 402 amino acids, with two common conserved SANT/Myb domains in N
      terminal. The BZcon1 knockout mutant completely lost the capability to produce
      conidiophores and conidia but displayed no effect on hyphal growth and sexual
      reproduction. The introduced BZcon1 gene fully complemented the BZcon1 null
      mutation, restoring the capability for sporulation. These data suggested that the
      BZcon1 gene is essential for the conidiation of C. carbonum. 

PMID- 24898710
TI  - A note regarding 'random effects'.

PMID- 24898711
TI  - Authors' reply to comments on 'Sample size calculation for comparing two negative
      binomial rates'.

PMID- 24898714
TI  - Perspectives in endocrine toxicity of heavy metals--a review.
AB  - An attempt has been made to review the endocrine/hormonal implications of a few
      environmentally significant metals, viz, lead, mercury, cadmium, copper, arsenic
      and nickel, in man and animals. Special emphasis has been given to the adrenals,
      thyroid, testis, ovary and pancreas. Toxic metals can cause structural and
      functional changes in the adrenal glands. Their effects on steroidogenesis have
      been reviewed. It has been reported that thyroid hormone kinetics are affected by
      a number of metallic compounds. Occupational exposure to a few of these metals
      can cause testicular injury and sex hormone disturbances. Protective effects of a
      few antioxidants on their reproductive toxicity have also been discussed.
      Information gathered on female reproductive toxicity of heavy metals shows that
      exposure to these metals can lead to disturbances in reproductive performance in
      exposed subjects. Certain metals can cause injury to the endocrine pancreas.
      Exposure to them can cause diabetes mellitus and disturb insulin homeostasis. The
      need to develop molecular markers of endocrine toxicity of heavy metals has been
      suggested. Overall information described in this review is expected to be helpful
      in planning future studies on endocrine toxicity of heavy metals. 

PMID- 24898715
TI  - Reprint: 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular
      Risk.

PMID- 24898712
TI  - Prevalence of hepatitis B virus infection in patients with rheumatic diseases in
      Tohoku area: a retrospective multicenter survey.
AB  - Hepatitis B virus (HBV) reactivation has been increasingly recognized in patients
      receiving chemotherapy and immunosuppressive therapy; however, the prevalence of
      HBV infection and rate of HBV screening in patients with rheumatic diseases
      remains unclear. In this study, we aimed to assess the prevalence of HBV
      infection and fulminant HBV hepatitis in patients with rheumatic diseases. We
      also investigated the rate of HBV screening before immunosuppressive therapy in
      patients with rheumatic diseases. A retrospective questionnaire survey was
      conducted in the North-east area (Tohoku) of Japan. Questionnaires, comprising 6
      questions, were sent to 318 rheumatologists in May 2010, and responses were
      gathered until June 2011. In total, 71 rheumatologists (22.3%) responded to the
      survey. We enrolled 7,650 patients with rheumatoid arthritis (RA) and 1,031
      patients with systemic lupus erythematosus (SLE). When limited to institutes at
      which almost all (>= 90%) patients were tested for HBV serology, 1.1% (40/3,580)
      patients with RA and 0.3% (3/1,128) patients with SLE were positive for hepatitis
      B surface antigen (HBsAg), and 25.2% (177/703) patients with RA and 13.7%
      (34/248) patients with SLE were positive for hepatitis B core antibody (HBcAb).
      About one-third of rheumatologists did not check HBsAg and more than half did not
      check hepatitis B surface antibody (HBsAb) or HBcAb at all before therapy.
      Fulminant HBV hepatitis was observed in 1 RA patient who was current HBV carrier.
      In conclusion, the prevalence of HBV infection is high in patients with RA and
      SLE. HBV screening before immunosuppressive therapy should be strictly performed.

PMID- 24898716
TI  - Reprint: 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity
      in Adults.

PMID- 24898717
TI  - Comparison between paediatric and adult suspected adverse drug reactions reported
      to the European medicines agency: implications for pharmacovigilance.
AB  - BACKGROUND: Databases systematically collecting reports of suspected adverse drug
      reactions (ADRs) are a cornerstone of pharmacovigilance in that they provide on
      going large-scale surveillance in the 'real-world' setting. Several studies have
      provided data on ADRs in children reported to national databases. EudraVigilance
      (EV) is the European Medicines Agency's (EMA) web-based system for reporting and
      evaluating suspected ADRs. Due to requirements on pharmaceutical companies to
      report ADRs that originate both inside and outside Europe, the data in
      EudraVigilance are global in nature. As such, it is potentially a rich source of
      information for paediatric pharmacovigilance. AIM: The present study sought to
      provide a descriptive overview comparing ADRs involving children and adolescents
      aged less than 18 years with those involving adults reported to EudraVigilance
      across national boundaries. The results will serve as a baseline to explore
      whether lessons can be learned for paediatric pharmacovigilance. METHODS: All ADR
      reports received in EudraVigilance up to 13 June 2013 were analysed for overall
      numbers, age, gender, and geographic origin. Accurate age was determined when
      reported in valid format or calculated from the interval between date of birth
      and the reaction start date. The nature of the ADRs and the most frequently
      reported drug substances and drug event combinations were evaluated using Medical
      Dictionary for Regulatory Activities (MedDRA) 'preferred terms' (PTs) and 'system
      organ classes' (SOCs). The distribution over time of reported paediatric ADRs was
      also analysed. RESULTS: As of 13 June 2013, EudraVigilance contained 3,291,593
      spontaneous reports, for 75.9 % of which accurate age was determined; 11.2 % of
      these were paediatric reports. Paediatric ADRs were more common than those in
      adults under the MedDRA SOCs 'general and administration site', 'nervous system',
      'skin and subcutaneous' and 'infections and infestations'. For children, the
      three most frequently reported MedDRA PTs, i.e. pyrexia, vomiting and convulsion
      (13, 6 and 4 % of reports, respectively), accounted for a greater proportion of
      reports than the corresponding top three in adults, i.e. nausea, dyspnoea and
      pyrexia (4, 4 and 3 % of reports, respectively). The 20 most reported active
      substances (12 of which are vaccines) together accounted for 52 % of paediatric
      reports as compared with 28 % of adult reports. CONCLUSIONS: The present study
      applied a first-time approach to one of the largest databases worldwide of
      reported ADRs. It confirmed that reports of reactions in children were different
      to those in adults, not only in terms of reactions and drugs involved but also
      more concentrated around limited sets of reaction types and drugs. The possible
      causal association between a medicine or vaccine and the suspected ADR was not
      formally assessed in this study since the study analysed the characteristics of
      reported ADRs that were suspected and therefore not proven. However, the findings
      may help to identify pharmacovigilance activities that should be strengthened to
      reduce the burden of ADRs in children.

PMID- 24898719
TI  - Endoscopic Internal Drainage with Enteral Nutrition (EDEN) for treatment of leaks
      following sleeve gastrectomy.
AB  - BACKGROUND: Endoscopic treatment of gastric leaks (GL) following sleeve
      gastrectomy (SG) involves different techniques; however, standard management is
      not yet established. We report our experience about endoscopic internal drainage
      of leaks using pigtail stents coupled with enteral nutrition (EDEN) for 4 to 6
      weeks until healing is achieved. METHODS: In 21 pts (18 F, 41 years), one or two
      plastic pigtail stents were delivered across the leak 25.6 days (4-98) post
      surgery. In all patients, nasojejunal tube was inserted. Check endoscopy was done
      at 4 to 6 weeks with either restenting if persistent leak, or removal if no
      extravasation of contrast in peritoneal cavity, or closure with an Over-the-Scope
      Clip(r) (OTSC(r)) if contrast opacifying the crossing stent without concomitant
      peritoneal extravasation. RESULTS: Twenty-one out of 21 (100 %) patients
      underwent check endoscopy at average of 30.15 days (26-45) from stenting. In 7/21
      (33.3 %) patients leak sealed, 2/7 needed OTSC(r). Second check endoscopy, 26.7
      days (25-42) later, showed sealed leak in 10 out 14; 6/10 had OTSC(r). Four
      required restenting. One patient, 28 days later, needed OTSC(r). One healed at
      135 days and another 180 days after four and seven changes, respectively. One
      patient is currently under treatment. In 20/21 (95.2 %), GL have healed with EID
      treatment of 55.5 days (26- 180); all are asymptomatic on a normal diet at
      average follow-up of 150.3 days (20-276). CONCLUSIONS: EDEN is a promising
      therapeutic approach for treating leaks following SG. Multiple endoscopic
      sessions may be required.

PMID- 24898721
TI  - Effect of a post-operative structured exercise programme on short-term weight
      loss after obesity surgery using adjustable gastric bands.
AB  - BACKGROUND: Exercise has been recommended as an adjunct to diet control to
      achieve weight loss. No previous studies in the area had formal exercise
      guidelines or education [1, 2]. Unique to our practice is Bandfit, a personal
      trainer-led exercise programme for patients following bariatric surgery. METHODS:
      We analysed the effect of Bandfit on short-term weight loss. A retrospective
      review of a prospectively collected database of consecutive patients between 2007
      and 2008 was undertaken. Patients were educated about appropriate exercises for
      obese people with active participation. Percentage excess weight loss was
      calculated at 12 and 36 months. Weights were accepted +/-3 months following the
      gastric banding. Patients were divided into subgroups based on zero, one or
      greater than one session attended. Patients without available records, 12-month
      data or a rural address were excluded. Data were statistically analysed utilising
      a two-sample t test and an analysis of variance (ANOVA) calculation. RESULTS: One
      hundred sixty-three patients were eligible for inclusion with 26 excluded as
      described in the methods. In the remaining 137 patients, 49 (36 %) did not attend
      any sessions, 28 (20 %) attended one, and 60 (44 %) attended more than one
      session. CONCLUSIONS: Analysis of the %EWL and sessions attended demonstrated a
      significant difference between those who attended more than one Bandfit session
      (p < 0.03), compared to those who did not attend any. However, this effect was
      not seen at 36 months. Attendance at a dedicated educational exercise programme
      significantly enhances short-term weight loss, but the effect is not seen at 36
      months.

PMID- 24898720
TI  - Duodenal-jejunal bypass surgery suppresses hepatic de novo lipogenesis and
      alleviates liver fat accumulation in a diabetic rat model.
AB  - BACKGROUND: Duodenal-jejunal bypass (DJB) surgery can induce rapid and durable
      remission of type 2 diabetes mellitus (T2DM), but the intrinsic mechanisms remain
      to be elucidated. Recent studies indicated that improved hepatic insulin
      resistance and insulin signaling transduction might contribute to the diabetic
      control after DJB. Given the important role of liver adiposity in hepatic insulin
      resistance, this study was aimed at investigating the effects of DJB on glucose
      homeostasis and liver fat accumulation in a T2DM rat model induced by high-fat
      diet (HFD) and small dose of streptozotocin (STZ). METHODS: Forty adult male
      diabetic rats induced by HFD and small dose of STZ were randomly assigned to sham
      and DJB groups. Body weight, calorie intake, hormone levels, glucose, and lipid
      parameters were measured at indicated time points. Subsequently, hepatic
      triglycerides (TG) content and the protein levels of sterol regulatory element
      binding protein-1 (SREBP-1), carbohydrate response element binding protein
      (ChREBP), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were
      evaluated at 2 and 8 weeks postoperatively. RESULTS: Compared with sham group,
      DJB induced rapid and significant improvements in glucose homeostasis and insulin
      sensitivity independently of weight loss and calorie restriction. The DJB
      operated rats exhibited lower liver TG content and decreased hepatic SREBP-1,
      ChREBP, ACC, and FAS at 8 weeks postoperatively. CONCLUSIONS: DJB alleviated
      hepatic fat accumulation and downregulated the key transcriptional regulators and
      enzymes involved in hepatic de novo lipogenesis, which might contribute to
      improved hepatic insulin sensitivity and glucose homeostasis after DJB.

PMID- 24898722
TI  - Reversible bilio-pancreatic diversion with explorable excluded stomach-the
      Messina technique.
AB  - The authors propose a reversible bilio-pancreatic diversion with access to the
      bypassed stomach. In the Messina technique, bilio-pancreatic diversion is
      accomplished by transecting the stomach without gastric resection, as already
      described by Resa et al. In addition, a temporary gastrostomy is performed on the
      excluded stomach and allows direct postoperative exploration of the duodenum and
      the biliary tree. The Messina bilio-pancreatic diversion technique (MBPDT) seems
      to be safe and effective. The authors propose the MBPDT in a morbidly obese
      patient undergoing bariatric surgery when a malabsorptive operation is required,
      as it makes the original Scopinaro operation reversible, the bilio-pancreatic
      area explorable postoperatively, the operation shorter, and does not cause any
      significant increase in the postoperative complication rate. Larger numbers and
      longer follow-up, however, are needed to further confirm our data. 

PMID- 24898709
TI  - Population dynamics and evolutionary history of the weedy vine Ipomoea hederacea
      in North America.
AB  - Disentangling the historical evolutionary processes that contribute to patterns
      of phenotypic and genetic variation is important for understanding contemporary
      patterns of both traits of interest and genetic diversity of a species. Ipomoea
      hederacea is a self-compatible species whose geographic origin is contested, and
      previous work suggests that although there are signals of adaptation (significant
      leaf shape and flowering time clines), no population structure or neutral genetic
      differentiation of I. hederacea populations was detected. Here, we use DNA
      sequence data to characterize patterns of genetic variation to establish a more
      detailed understanding of the current and historical processes that may have
      generated the patterns of genetic variation in this species. We resequenced ca.
      5000 bp across 7 genes for 192 individuals taken from 24 populations in North
      America. Our results indicate that North American I. hederacea populations are
      ubiquitously genetically depauperate, and patterns of nucleotide diversity are
      consistent with population expansion. Contrary to previous findings, we
      discovered significant population subdivision and isolation-by-distance, but
      genetic structure was spatially discontinuous, potentially implicating long
      distance dispersal. We further found significant genetic differentiation at
      sequenced loci but nearly fourfold stronger differentiation at the leaf shape
      locus, strengthening evidence that the leaf shape locus is under divergent
      selection. We propose that North American I. hederacea has experienced a recent
      founder event, and/or population dynamics are best described by a metapopulation
      model (high turnover and dispersal), leading to low genetic diversity and a
      patchy genetic distribution. 

PMID- 24898718
TI  - The pharmacologic management of delirium in children and adolescents.
AB  - Delirium is a serious and common problem in severely medically ill patients of
      all ages. It has been less addressed in children and adolescents. Treatment of
      delirium is predicated on addressing its underlying cause. The management of its
      symptoms depends on the off-label use of antipsychotics, while avoiding agents
      that precipitate or worsen delirium. Olanzapine, quetiapine, and risperidone are
      presently considered first-line drugs, usually replacing haloperidol. Other
      agents have shown promise, including melatonin to address the sleep disturbance
      characteristic of delirium, and dexmedetomidine, an alpha2-agonist, that may
      facilitate lower doses of benzodiazepines and opioids that may worsen delirium. 

PMID- 24898723
TI  - HILIC-MS-based shotgun metabolomic profiling of maternal urine at 9-23 weeks of
      gestation - establishing the baseline changes in the maternal metabolome.
AB  - In this data-rich age it is no longer necessary to methodically isolate,
      characterize and measure specific molecules. What is important is to identify
      which of the hundreds or thousands of resolved and measured 'unknown' molecules
      are potentially associated with the pathophysiology of interest. We have taken LC
      MS data from pregnancy urine and applied SIMCA P+ data analysis software in
      shotgun metabolomics to search the large amount of data for significant
      metabolite changes that occur in the transition from the first to early second
      trimester of pregnancy. Seventy-two individual urine samples were examined
      spanning 9-23 weeks of gestation. Three-hundred and eighty-three ions were
      identified and variations were mapped between profiles of different gestational
      age and the significance quantified. In urine collected during pregnancy, the
      transition from first to early second trimester revealed a relatively steady
      pattern of metabolites except for four that showed a dramatic fall in abundance
      as pregnancy progressed from the first to second trimester. The pattern of
      changes in urinary metabolites identified by Zwitterionic Hydrophilic Liquid
      Interaction Chromatography (ZIC-HILIC) coupled to mass spectrometry was evaluated
      and we established a baseline of changes from which a search for metabolomic
      markers associated with clinical pathologies of pregnancy can be made as a part
      of wider ultraomics study.

PMID- 24898724
TI  - Application of liquid-based transepithelial flexible brush cytology in the
      detection of high-grade laryngeal mucosal lesions.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of liquid
      based transepithelial flexible brush cytology (LBTFBC) in the detection of high
      grade laryngeal mucosal lesions. METHODS: Diagnostic accuracies of LBTFBC and
      flexible biopsy (FB) were compared with the gold standard of biopsy under general
      anaesthesia (BUA) in 49 and 46 patients, respectively. Using a flexible
      laryngoscope, transepithelial cytology and biopsy specimens were obtained with
      the aid of flexible brushes and biopsy forceps. Cytology specimens were graded
      and scored using a recently proposed oral cytologic grading and scoring system.
      RESULTS: Cytology showed 97, 29% sensitivity, 100% specificity, 97.9% accuracy,
      and FB disclosed 77.1% sensitivity, 100% specificity, and 82.2% accuracy when
      compared with BUA. The best cutoff value for discriminating reactive/mildly
      dysplastic lesions from high-grade dysplasias/invasive squamous cell carcinomas
      (SCCs) was determined as a cytologic score of 3, with sensitivity and specificity
      of 100%. CONCLUSION: LBTFBC is a simple office-based procedure, which in
      combination with the newly proposed classification scheme appears to be an
      accurate technique in the detection of high-grade laryngeal mucosal lesions.
      LBTFBC is more effective than FB owing to the enhanced range of sampling and ease
      of application. It effectively eliminates the need for general anaesthesia, and
      thus reducing theatre costs and the number of hospital admissions. LBTFBC is
      ideal for patients who require regular clinical examinations, where repeated
      biopsies may lead to significant vocal morbidity.

PMID- 24898725
TI  - Young children make their gestural communication systems more language-like:
      segmentation and linearization of semantic elements in motion events.
AB  - Research on Nicaraguan Sign Language, created by deaf children, has suggested
      that young children use gestures to segment the semantic elements of events and
      linearize them in ways similar to those used in signed and spoken languages.
      However, it is unclear whether this is due to children's learning processes or to
      a more general effect of iterative learning. We investigated whether typically
      developing children, without iterative learning, segment and linearize
      information. Gestures produced in the absence of speech to express a motion event
      were examined in 4-year-olds, 12-year-olds, and adults (all native English
      speakers). We compared the proportions of gestural expressions that segmented
      semantic elements into linear sequences and that encoded them simultaneously.
      Compared with adolescents and adults, children reshaped the holistic stimuli by
      segmenting and recombining their semantic features into linearized sequences. A
      control task on recognition memory ruled out the possibility that this was due to
      different event perception or memory. Young children spontaneously bring
      fundamental properties of language into their communication system. 

PMID- 24898726
TI  - The commitment function of angry facial expressions.
AB  - What function do facial expressions have? We tested the hypothesis that some
      expressions serve as honest signals of subjective commitments-in particular, that
      angry faces increase the effectiveness of threats. In an ultimatum game,
      proposers decided how much money to offer a responder while seeing a film clip
      depicting an angry or a neutral facial expression, together with a written threat
      that was either inherently credible (a 50-50 split) or less credible (a demand
      for 70% of the money). Proposers offered greater amounts in response to the less
      credible threat when it was accompanied by an angry expression than when it was
      accompanied by a neutral expression, but were unaffected by the expression when
      dealing with the credible threat. This finding supports the hypothesis that angry
      expressions are honest signals that enhance the credibility of threats. 

PMID- 24898728
TI  - Mites (Acari, Mesostigmata) in boreal Scots pine forest floors: effect of
      distance to stumps.
AB  - Coarse woody debris (CWD) is a basic component of forest ecosystems and it plays
      a crucial role in species-poor boreal forests. Generally, previous studies have
      focused on differences between the forest floor and decaying logs of various tree
      species. The impact of distance to CWD has been investigated mainly for forest
      floor snails and some groups of macrofauna, but not yet for mesostigmatid mites
      communities. We hypothesized that the effect of CWD decreases with increasing
      distance from CWD. To test this hypothesis we conducted a study in relatively
      species-poor Finnish boreal forest (at ca. 100 km northwest of Helsinki). In
      total, 81 samples were collected in 2007 from nine Scots pine (Pinus sylvestris)
      stumps, three microhabitats (CWD, soil/litter at 0.5 m from a stump and
      soil/litter at 1.5 m from a stump) and in three main directions (9 stumps * 3
      microhabitats * 3 directions). Overall, 1965 mesostigmatid mites were collected
      representing 24 species. The mean number of mite species collected was
      significantly different between decaying stumps and forest litter; however, there
      was no significant difference between the litter samples at 0.5 and 1.5 m
      distance. The evenness index was significantly lower for samples collected from
      stumps than for litter in close (0.5 m) or far (1.5 m) distance. The most
      frequently encountered mite species were Veigaia nemorensis, Parazercon radiatus
      and Zercon zelawaiensis. 

PMID- 24898727
TI  - B-cell receptor-associated protein 31 regulates human embryonic stem cell
      adhesion, stemness, and survival via control of epithelial cell adhesion
      molecule.
AB  - B-Cell receptor-associated protein 31 (BAP31) regulates the export of secreted
      membrane proteins from the endoplasmic reticulum (ER) to the downstream secretory
      pathway. Previously, we generated a monoclonal antibody 297-D4 against the
      surface molecule on undifferentiated human embryonic stem cells (hESCs). Here, we
      found that 297-D4 antigen was localized to pluripotent hESCs and downregulated
      during early differentiation of hESCs and identified that the antigen target of
      297-D4 was BAP31 on the hESC-surface. To investigate the functional role of BAP31
      in hESCs, BAP31 expression was knocked down by small interfering RNA. BAP31
      depletion impaired hESC self-renewal and pluripotency and drove hESC
      differentiation into multicell lineages. BAP31 depletion hindered hESC
      proliferation by arresting cell cycle at G0/G1 phase and inducing caspase
      independent cell death. Interestingly, BAP31 depletion reduced hESC adhesion to
      extracellular matrix (ECM). Analysis of cell surface molecules showed decreased
      expression of epithelial cell adhesion molecule (EpCAM) in BAP31-depleted hESCs,
      while ectopic expression of BAP31 elevated the expression of EpCAM. EpCAM
      depletion also reduced hESC adhesion to ECM, arrested cell cycle at G0/G1 phase
      and induced cell death, producing similar effects to those of BAP31 depletion.
      BAP31 and EpCAM were physically associated and colocalized at the ER and cell
      surface. Both BAP31 and EpCAM depletion decreased cyclin D1 and E expression and
      suppressed PI3K/Akt signaling, suggesting that BAP31 regulates hESC stemness and
      survival via control of EpCAM expression. These findings provide, for the first
      time, mechanistic insights into how BAP31 regulates hESC stemness and survival
      via control of EpCAM expression.

PMID- 24898730
TI  - Assessing medication adherence using indirect self-report.

PMID- 24898729
TI  - Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates
      viral replication by disrupting NS4B self-interaction.
AB  - The non-structural protein 4B (NS4B) of the hepatitis C virus (HCV) is an
      endoplasmic reticulum (ER) membrane protein comprising two consecutive
      amphipathic alpha-helical domains (AH1 and AH2). Its self-oligomerization via the
      AH2 domain is required for the formation of the membranous web that is necessary
      for viral replication. Previously, we reported that the host-encoded ER
      associated reticulon 3 (RTN3) protein is involved in the formation of the
      replication-associated membranes of (+)RNA enteroviruses during viral
      replication. In this study, we demonstrated that the second transmembrane region
      of RTN3 competed for, and bound to, the AH2 domain of NS4B, thus abolishing NS4B
      self-interaction and leading to the downregulation of viral replication. This
      interaction was mediated by two crucial residues, lysine 52 and tyrosine 63, of
      AH2, and was regulated by the AH1 domain. The silencing of RTN3 in Huh7 and AVA5
      cells harbouring an HCV replicon enhanced the replication of HCV, which was
      counteracted by the overexpression of recombinant RTN3. The synthesis of viral
      RNA was also increased in siRNA-transfected human primary hepatocytes infected
      with HCV derived from cell culture. Our results demonstrated that RTN3 acted as a
      restriction factor to limit the replication of HCV. 

PMID- 24898732
TI  - Infertility caused by intrauterine fetal bone retention: a case report.
AB  - INTRODUCTION: Intrauterine fetal bone retention is a rare complication and the
      bony fragments probably work like an intrauterine contraceptive device resulting
      in secondary infertility. Among the scarcely reported cases in the literature,
      there was no report described the retention of a large number of fetal bones with
      nearly intact morphology. CASE PRESENTATION: The present report described an
      unusual case of fetal bone retention in a 30-year-old infertile Chinese woman who
      had a surgical termination of a 15-week pregnancy 9 years ago. The routine B
      ultrasound diagnosed intrauterine foreign bodies. A hysteroscopy was performed
      which showed a large number of intrauterine bony fragments, with clear fetal
      skeletal outline and intact morphology. The detected residual fetal bones were
      removed under hysteroscopy, assisted by B-ultrasound scanning. The patient was
      pregnant 5 months later. The present case confirms the importance of routine
      examination of the intactness of the fetus after abortion, particularly when it
      happens in pregnancies of more than 12 weeks. Once diagnosed, the detected
      residual fetal bones should be removed by surgery, mainly under hysteroscopy.
      CONCLUSIONS: The retention of fetal bone may cause infertility, and removal of
      the residual bone may restore fertility. The improvement in hysteroscopy made it
      feasible to diagnose and remove the bones. The present case highlights the
      importance of examining the intactness of the removed fetus.

PMID- 24898731
TI  - A recently transferred cluster of bacterial genes in Trichomonas vaginalis-
      lateral gene transfer and the fate of acquired genes.
AB  - BACKGROUND: Lateral Gene Transfer (LGT) has recently gained recognition as an
      important contributor to some eukaryote proteomes, but the mechanisms of
      acquisition and fixation in eukaryotic genomes are still uncertain. A previously
      defined norm for LGTs in microbial eukaryotes states that the majority are genes
      involved in metabolism, the LGTs are typically localized one by one, surrounded
      by vertically inherited genes on the chromosome, and phylogenetics shows that a
      broad collection of bacterial lineages have contributed to the transferome.
      RESULTS: A unique 34 kbp long fragment with 27 clustered genes (TvLF) of
      prokaryote origin was identified in the sequenced genome of the protozoan
      parasite Trichomonas vaginalis. Using a PCR based approach we confirmed the
      presence of the orthologous fragment in four additional T. vaginalis strains.
      Detailed sequence analyses unambiguously suggest that TvLF is the result of one
      single, recent LGT event. The proposed donor is a close relative to the firmicute
      bacterium Peptoniphilus harei. High nucleotide sequence similarity between T.
      vaginalis strains, as well as to P. harei, and the absence of homologs in other
      Trichomonas species, suggests that the transfer event took place after the
      radiation of the genus Trichomonas. Some genes have undergone pseudogenization
      and degradation, indicating that they may not be retained in the future.
      Functional annotations reveal that genes involved in informational processes are
      particularly prone to degradation. CONCLUSIONS: We conclude that, although the
      majority of eukaryote LGTs are single gene occurrences, they may be acquired in
      clusters of several genes that are subsequently cleansed of evolutionarily less
      advantageous genes.

PMID- 24898733
TI  - Three-dimensional graphene oxide: a promising green and sustainable catalyst for
      oxidation reactions at room temperature.
AB  - Three-dimensional graphene oxide foam (3DGO) was found to be a highly efficient
      and recyclable catalyst for the oxidation of thioanisole. We found that 3DGO is
      more efficient than 2DGO, and that the efficiency increases with the number of
      cycles for 3DGO, in contrast to the 2D counterpart. 

PMID- 24898735
TI  - An update to the Raymond-Roy Occlusion Classification of intracranial aneurysms
      treated with coil embolization.
AB  - BACKGROUND: The Raymond-Roy Occlusion Classification (RROC) is the standard for
      evaluating coiled aneurysms (Class I: complete obliteration; Class II: residual
      neck; Class III: residual aneurysm), but not all Class III aneurysms behave the
      same over time. METHODS: This is a retrospective review of 370 patients with 390
      intracranial aneurysms treated with coil embolization. A Modified Raymond-Roy
      Classification (MRRC), in which Class IIIa designates contrast within the coil
      interstices and Class IIIb contrast along the aneurysm wall, was applied
      retrospectively. RESULTS: Class IIIa aneurysms were more likely to improve to
      Class I or II than Class IIIb aneurysms (83.34% vs 14.89%, p<0.001) and were also
      more likely than Class II to improve to Class I (52.78% vs 16.90%, p<0.001).
      Class IIIb aneurysms were more likely to remain incompletely occluded than Class
      IIIa aneurysms (85.11% vs 16.67%, p<0.001). Class IIIb aneurysms were larger with
      wider necks while Class IIIa aneurysms had higher packing density. Class IIIb
      aneurysms had a higher retreatment rate (33.87% vs 6.54%, p<0.001) and a trend
      toward higher subsequent rupture rate (3.23% vs 0.00%, p=0.068). CONCLUSIONS: We
      propose the MRRC to further differentiate Class III aneurysms into those likely
      to progress to complete occlusion and those likely to remain incompletely
      occluded or to worsen. The MRRC has the potential to expand the definition of
      adequate coil embolization, possibly decrease procedural risk, and help
      endovascular neurosurgeons predict which patients need closer angiographic follow
      up. These findings need to be validated in a prospective study with independent
      blinded angiographic grading.

PMID- 24898736
TI  - Deep MicroRNA sequencing reveals downregulation of miR-29a in neuroblastoma
      central nervous system metastasis.
AB  - Central nervous system (CNS) is an increasingly common site of isolated
      metastasis for patients with Stage 4 neuroblastoma. To explore the microRNA
      (miRNA) profile of this metastatic process, miRNA sequencing was performed to
      identify miRNA sequence families with differential expression between tumor pairs
      (pre-CNS primary and CNS metastasis) from 13 patients with Stage 4 neuroblastoma.
      Seven miRNA sequence families had distinct expression in CNS metastases when
      compared with their corresponding pre-CNS primaries. MiR-7 was upregulated (3.75
      fold), and miR-21, miR-22, miR-29a, miR-143, miR-199a-1-3p, and miR-199a-1-5p
      were downregulated (3.5-6.1-fold), all confirmed by quantitative reverse
      transcription-PCR. MiR-29a, previously shown to be downregulated in a broad
      spectrum of solid tumors including neuroblastoma, had the most significant
      decrease in all 13 CNS metastases (P = 0.001). Its known onco-targets CDC6, CDK6,
      and DNMT3A, as well as B7-H3, an inhibitory ligand for T cells, and natural
      killer cells, were found to have higher differential expression in these 13 CNS
      metastases when compared with their paired primaries. Additionally, miR-29a
      expression in primary tumors was significantly lower among patients who
      eventually relapsed in the CNS. Irrespective of the amplification status of MYCN,
      which is known to be associated with metastasis, pre-CNS primaries, and CNS
      metastases had significantly lower miR-29a expression than non-CNS primary
      tumors. Among MYCN amplified cell lines, those from CNS relapse also had lower
      miR-29a expression than non-CNS relapse. These findings raised the hypothesis
      that miR-29a could be a biomarker for neuroblastoma CNS metastasis, and its
      downregulation may play a pivotal role in CNS progression.

PMID- 24898734
TI  - Quantitative determination of binding of ISWI to nucleosomes and DNA shows
      allosteric regulation of DNA binding by nucleotides.
AB  - The regulation of chromatin structure is controlled by a family of molecular
      motors called chromatin remodelers. The ability of these enzymes to remodel
      chromatin structure is dependent on their ability to couple ATP binding and
      hydrolysis into the mechanical work that drives nucleosome repositioning. The
      necessary first step in determining how these essential enzymes perform this
      function is to characterize both how they bind nucleosomes and how this
      interaction is regulated by ATP binding and hydrolysis. With this goal in mind,
      we monitored the interaction of the chromatin remodeler ISWI with fluorophore
      labeled nucleosomes and DNA through associated changes in fluorescence anisotropy
      of the fluorophore upon binding of ISWI to these substrates. We determined that
      one ISWI molecule binds to a 20 bp double-stranded DNA substrate with an affinity
      of 18 +/- 2 nM. In contrast, two ISWI molecules can bind to the core nucleosome
      with short linker DNA with stoichiometric macroscopic equilibrium constants:
      1/beta1 = 1.3 +/- 0.6 nM, and 1/beta2 = 13 +/- 7 nM(2). Furthermore, to improve
      our understanding of the mechanism of DNA translocation by ISWI, and hence
      nucleosome repositioning, we determined the effect of nucleotide analogues on
      substrate binding by ISWI. While the affinity of ISWI for the nucleosome
      substrate with short lengths of flanking DNA was not affected by the presence of
      nucleotides, the affinity of ISWI for the DNA substrate is weakened in the
      presence of nonhydrolyzable ATP analogues but not by ADP. 

PMID- 24898737
TI  - Supporting Pakistani and Chinese families with young children: perspectives of
      mothers and health visitors.
AB  - BACKGROUND: In the UK, public health nurses (health visitors) provide support and
      advice to families with young children, including those from minority ethnic
      communities. While the need for cultural sensitivity is being increasingly
      recognized, the factors which contribute to this sensitivity are poorly
      understood. The Pakistani and Chinese communities constitute the two largest
      minority ethnic groups in Scotland. This study explored Pakistani and Chinese
      women's experience of motherhood and of the health visiting service and public
      health nurses' experiences of working with Chinese and Pakistani mothers.
      METHODS: Semi-structured individual interviews were carried out with 16 Pakistani
      and 15 Chinese mothers. Eight health visitors took part in two focus groups. The
      study was undertaken in an urban area of Scotland. Data were analysed
      thematically. FINDINGS: Chinese and Pakistani mothers negotiate complex processes
      in order to ensure that their children maintain their own ethnic identity while
      fitting in with their peers in their adopted country. Health visitors were seen
      as supportive, although sometimes advice and information given was culturally
      inappropriate, and their role was often poorly understood. Health visitors were
      anxious to be sensitive to families' religious and cultural beliefs. CONCLUSIONS:
      Cultural sensitivity is an important factor in providing appropriate advice and
      help to Pakistani and Chinese families, and involves health visitors in
      considering views and practices on parenting which may differ across cultures,
      including their own. Family characteristics need to be understood on an
      individual basis, rather than making assumptions about clients' cultural norms
      and lifestyles. This is best achieved by exploring with mothers if they
      understand the advice and information they are being offered and also if it is
      appropriate to their cultural and religious beliefs.

PMID- 24898738
TI  - Uremic pruritus is improved by gabapentin.

PMID- 24898739
TI  - Headaches, quality of life, and academic performance in schoolchildren and
      adolescents.
AB  - BACKGROUND: Just a few studies to date have focused on headaches, quality of
      life, and academic performance in children. OBJECTIVE: Determine the effect of
      headaches on the life of schoolchildren and the association between headaches and
      academic performance. METHODS: We conducted a cross-sectional study. One hundred
      and ninety-five students from an elementary school were randomly selected out of
      355 students aged from 10 to 15 years old. Semi-structured interview, the
      Pediatric Quality of Life Inventory Version 4.0, the Children's Depression
      Inventory, and the State-Trait Anxiety Inventory were used. The variables
      relating to academic performance were obtained by consulting the academic
      records. RESULTS: Prevalence of headaches: headache: 97.3% (179/184); migraine:
      51% (94/184); tension-type headache: 33% (61/184); primary stabbing headache:
      7.6% (14/184); unclassified headaches: 5.4% (10/184). Migraine (relative risk:
      3.11; 95% confidence interval: 1.54-6.30) and more severe headaches (relative
      risk: 7.93; 95% confidence interval: 2.65-23.7) were associated with lower
      quality of life (P < .01; multivariate logistic regression). More severe
      headaches were associated with lower grades in school (P < .01; multiple linear
      regression). Variables relating to headaches were not associated with "failing
      the school year" (P > .05; chi-square test and Fisher's exact test). CONCLUSION:
      Headaches were found to be associated with lower quality of life and poor
      academic performance.

PMID- 24898740
TI  - A review of available analytical technologies for qualitative and quantitative
      determination of nitramines.
AB  - This review aims to summarize the available analytical methods in the open
      literature for the determination of some aliphatic and cyclic nitramines.
      Nitramines covered in this review are the ones that can be formed from the use of
      amines in post-combustion CO2 capture (PCC) plants and end up in the environment.
      Since the literature is quite scarce regarding the determination of nitramines in
      aqueous and soil samples, methods for determination of nitramines in other
      matrices have also been included. Since the nitramines are found in complex
      matrices and/or in very low concentration, an extraction step is often necessary
      before their determination. Liquid-liquid extraction (LLE) using dichloromethane
      and solid phase extraction (SPE) with an activated carbon based material have
      been the two most common extraction methods. Gas chromatography (GC) or reversed
      phase liquid chromatography (RPLC) has been used often combined with mass
      spectrometry (MS) in the final determination step. Presently there is no
      comprehensive method available that can be used for determination of all
      nitramines included in this review. The lowest concentration limit of
      quantification (cLOQ) is in the ng L(-1) range, however, most methods appear to
      have a cLOQ in the MUg L(-1) range, if the cLOQ has been given.

PMID- 24898741
TI  - Cardiovascular genetics: paying individual dividends.

PMID- 24898742
TI  - Endothelial insights: the Florian dialectic.
AB  - In heart healing, engineering technology has driven translation by bridging
      biology and medicine. 

PMID- 24898743
TI  - Atherosclerosis--multiple pathways to lesional macrophages.
AB  - Atherosclerosis is a chronic inflammatory disease that manifests in multiple
      vascular beds and frequently culminates in ischemic events, including myocardial
      infarction. Blood monocytes that are recruited to the inflamed vascular wall
      develop into inflammatory macrophages and foam cells, which contribute to
      pathogenesis at many stages of this disease and, therefore, represent a target
      for therapeutic interventions. Recently, alternate sources of macrophages have
      been identified. Here, we discuss the origin and molecular regulation of
      macrophages and highlight recent conceptual changes that may shape the
      development of effective treatments.

PMID- 24898745
TI  - New therapies for coronary artery disease: genetics provides a blueprint.
AB  - The development of new therapies for coronary artery disease (CAD) poses a
      substantial challenge, and several recent approaches have failed for lack of
      efficacy. Human genetics has the potential to identify new targets for which the
      likelihood of therapeutic success is considerably greater. The intense focus on
      the genetics of CAD will revitalize the field and lead to future therapies for
      this common disease.

PMID- 24898744
TI  - MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease.
AB  - MicroRNAs play central roles in cardiovascular disease, and their therapeutic
      manipulation raises exciting opportunities as well as challenges in the path
      toward clinical development.

PMID- 24898746
TI  - Common therapeutic targets in cardiometabolic disease.
AB  - The interactions between cardiovascular disease (CVD) and insulin resistance
      syndromes suggest the possibility of joint targets for cardiometabolic research.
      The best drugs would go beyond minimizing adverse effects and have protective
      actions against both metabolic disease and CVD. In this perspective, we will
      outline a few examples in which a deep mechanistic understanding of the many
      cellular pathways that contribute to type 2 diabetes and CVD, regardless of cell
      type, have resulted in common upstream pathogenic pathways that can be
      therapeutically targeted.

PMID- 24898747
TI  - Human stem cells for modeling heart disease and for drug discovery.
AB  - A major research focus in the field of cardiovascular medicine is the prospect of
      using stem cells and progenitor cells for cardiac regeneration. With the advent
      of induced pluripotent stem cell (iPSC) technology, major efforts are also
      underway to use iPSCs to model heart disease, to screen for new drugs, and to
      test candidate drugs for cardiotoxicity. Here, we discuss recent advances in the
      exciting fields of stem cells and cardiovascular disease.

PMID- 24898748
TI  - Strategies for cardiac regeneration and repair.
AB  - Heart failure is a growing epidemic caused by cardiomyocyte depletion. Current
      therapies prolong survival by protecting remaining cardiomyocytes but are unable
      to overcome the fundamental problem of regenerating lost cardiomyocytes. Several
      strategies for promoting heart regeneration have emerged from decades of
      intensive study. Although some of these strategies remain confined to basic
      research, others are beginning to be tested in humans. We review strategies for
      cardiac regeneration and summarize progress of related clinical trials.

PMID- 24898750
TI  - Chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating
      and life-threatening complication of acute pulmonary embolism. CTEPH results from
      persistent obstruction of pulmonary arteries and progressive vascular
      remodelling. Not all patients presenting with CTEPH have a history of clinically
      overt pulmonary embolism. The diagnostic work-up to detect or rule out CTEPH
      should include ventilation-perfusion scintigraphy, which has high sensitivity and
      a negative predictive value of nearly 100%. CT angiography usually reveals
      typical features of CTEPH, including mosaic perfusion, part or complete occlusion
      of pulmonary arteries, and intraluminal bands and webs. Patients with suspected
      CTEPH should be referred to a specialist centre for right-heart catheterisation
      and pulmonary angiography. Surgical pulmonary endarterectomy remains the
      treatment of choice for CTEPH and is associated with excellent long-term results
      and a high probability of cure. For patients with inoperable CTEPH, various
      medical and interventional therapies are being developed. 

PMID- 24898751
TI  - Colorimetric detection of Shewanella oneidensis based on immunomagnetic capture
      and bacterial intrinsic peroxidase activity.
AB  - Rapid detection and enumeration of target microorganisms is considered as a
      powerful tool for monitoring bioremediation process that typically involves
      cleaning up polluted environments with functional microbes. A novel colorimetric
      assay is presented based on immunomagnetic capture and bacterial intrinsic
      peroxidase activity for rapidly detecting Shewanella oneidensis, an important
      model organism for environmental bioremediation because of its remarkably diverse
      respiratory abilities. Analyte bacteria captured on the immunomagnetic beads
      provided a bacterial out-membrane peroxidase-amplified colorimetric readout of
      the immunorecognition event by oxidizing 3, 3', 5, 5'-tetramethylbenzidine (TMB)
      in the present of hydrogen peroxide. The high-efficiency of immunomagnetic
      capture and signal amplification of peroxidase activity offers an excellent
      detection performance with a wide dynamic range between 5.0 * 10(3) and 5.0 *
      10(6) CFU/mL toward target cells. Furthermore, this method was demonstrated to be
      feasible in detecting S. oneidensis cells spiked in environmental samples. The
      proposed colorimetric assay shows promising environmental applications for rapid
      detection of target microorganisms. 

PMID- 24898752
TI  - Multiple hereditary exostoses and ischiofemoral impingement: a case-control
      study.
AB  - OBJECTIVE: To assess whether there is a significant difference in the
      ischiofemoral space in patients with multiple hereditary exostoses affecting the
      proximal femora compared to normal patients. INTRODUCTION: Ischiofemoral
      impingement is an increasingly recognized cause of hip and buttock pain. This
      causes narrowing of the ischiofemoral space resulting in an abnormal quadratus
      femoris muscle. MATERIALS AND METHODS: We performed a retrospective search for
      individuals with MHE with proximal femoral involvement on pelvic MRI over a 7
      year period (2006-2013). Suitable patients were age- and sex-matched with a
      control group. The minimum ischiofemoral space (MIFS) was recorded in each hip,
      as was the presence of edema and atrophy of quadratus femoris and concomitant hip
      osteoarthrosis. MRI features suggestive of ischiofemoral impingement were defined
      as MIFS less than 10 mm or an abnormal quadratus femoris muscle. RESULTS: Twenty
      one hips in 11 individuals with MHE were included in the study. A total of 42
      hips were analyzed. The mean age was 37 years (range, 13-72 years) and 55% were
      male. There was a significant difference (p < 0.05) in the MIHS in individuals
      with MHE (mean, 10.7 mm, range, 0-21 mm) compared to a control group (mean, 18.1
      mm, range, 10.5-26.5 mm). MRI features suggestive of ischiofemoral impingement
      were seen in 13/21 (62%) hips in the MHE group and 0/21 (0%) in the control
      group. CONCLUSIONS: The reduced ischiofemoral space and associated quadratus
      femoris abnormalities in patients with MHE involving the proximal femora may
      account for hip/buttock symptoms in the absence of significant degenerative
      change.

PMID- 24898749
TI  - Imaging and nanomedicine in inflammatory atherosclerosis.
AB  - Bioengineering provides unique opportunities to better understand and manage
      atherosclerotic disease. The field is entering a new era that merges the latest
      biological insights into inflammatory disease processes with targeted imaging and
      nanomedicine. Preclinical cardiovascular molecular imaging allows the in vivo
      study of targeted nanotherapeutics specifically directed toward immune system
      components that drive atherosclerotic plaque development and complication. The
      first multicenter trials highlight the potential contribution of multimodality
      imaging to more efficient drug development. This review describes how the
      integration of engineering, nanotechnology, and cardiovascular immunology may
      yield precision diagnostics and efficient therapeutics for atherosclerosis and
      its ischemic complications.

PMID- 24898753
TI  - Mof-associated complexes have overlapping and unique roles in regulating
      pluripotency in embryonic stem cells and during differentiation.
AB  - The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem
      cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of
      two different HAT complexes, MSL and NSL. The individual contribution of MSL and
      NSL to transcription regulation in mESCs is not well understood. Our genome-wide
      analysis show that i) MSL and NSL bind to specific and common sets of expressed
      genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene
      bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is
      the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and
      bivalent genes. MSL is important to keep a subset of bivalent genes silent in
      mESCs, while developmental genes require MSL for expression during
      differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific
      sets of expressed genes in mESCs and during differentiation. 

PMID- 24898755
TI  - A user-friendly, open-source tool to project impact and cost of diagnostic tests
      for tuberculosis.
AB  - Most models of infectious diseases, including tuberculosis (TB), do not provide
      results customized to local conditions. We created a dynamic transmission model
      to project TB incidence, TB mortality, multidrug-resistant (MDR) TB prevalence,
      and incremental costs over 5 years after scale-up of nine alternative diagnostic
      strategies. A corresponding web-based interface allows users to specify local
      costs and epidemiology. In settings with little capacity for up-front investment,
      same-day microscopy had the greatest impact on TB incidence and became cost
      saving within 5 years if delivered at $10/test. With greater initial investment,
      population-level scale-up of Xpert MTB/RIF or microcolony-based culture often
      averted 10 times more TB cases than narrowly-targeted strategies, at minimal
      incremental long-term cost. Xpert for smear-positive TB had reasonable impact on
      MDR-TB incidence, but at substantial price and little impact on overall TB
      incidence and mortality. This user-friendly modeling framework improves decision
      makers' ability to evaluate the local impact of TB diagnostic strategies. 

PMID- 24898754
TI  - High-resolution mapping reveals hundreds of genetic incompatibilities in
      hybridizing fish species.
AB  - Hybridization is increasingly being recognized as a common process in both animal
      and plant species. Negative epistatic interactions between genes from different
      parental genomes decrease the fitness of hybrids and can limit gene flow between
      species. However, little is known about the number and genome-wide distribution
      of genetic incompatibilities separating species. To detect interacting genes, we
      perform a high-resolution genome scan for linkage disequilibrium between unlinked
      genomic regions in naturally occurring hybrid populations of swordtail fish. We
      estimate that hundreds of pairs of genomic regions contribute to reproductive
      isolation between these species, despite them being recently diverged. Many of
      these incompatibilities are likely the result of natural or sexual selection on
      hybrids, since intrinsic isolation is known to be weak. Patterns of genomic
      divergence at these regions imply that genetic incompatibilities play a
      significant role in limiting gene flow even in young species. 

PMID- 24898757
TI  - 18pi-Electron tautomeric benziphthalocyanine: a functional near-infrared dye with
      tunable aromaticity.
AB  - Dihydroxybenziphthalocyanine 1, with bulky aryloxy groups, has been synthesized
      and characterized by X-ray crystallography, NMR and UV/Vis-NIR spectroscopy, and
      theoretical calculations. Macrocycle 1 is the first example of an aromatic
      benziphthalocyanine with an 18pi-electron structure, and was found to exist as an
      equilibrium mixture of weakly aromatic and strongly aromatic tautomers. The
      aromaticity and near-IR absorption can be controlled by chemical modification at
      the reactive resorcinol moiety and by variation of the solvent. 

PMID- 24898759
TI  - Unexpected outcome of pallidal deep brain stimulation in a patient with Tourette
      syndrome.
AB  - A 30-year-old man underwent bilateral GPi DBS for refractory TS. His tics and
      obsessive-compulsive symptoms were significantly improved after chronic
      stimulation. At 22 months postoperatively, the implantable pulse generator had to
      be removed because of an infection in the infraclavicular pouch. However, we
      observed an unexpected effectiveness at follow-up more than 4 years after
      stopping the stimulation. This is the first case report of TS that showed a
      favorable long-term outcome after cessation of chronic GPi DBS.

PMID- 24898756
TI  - Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable
      metastatic traits in breast cancer.
AB  - The mechanisms through which cancer cells lock in altered transcriptional
      programs in support of metastasis remain largely unknown. Through integrative
      analysis of clinical breast cancer gene expression datasets, cell line models of
      breast cancer progression, and mutation data from cancer genome resequencing
      studies, we identified RNA binding motif protein 47 (RBM47) as a suppressor of
      breast cancer progression and metastasis. RBM47 inhibited breast cancer re
      initiation and growth in experimental models. Transcriptome-wide HITS-CLIP
      analysis revealed widespread RBM47 binding to mRNAs, most prominently in introns
      and 3'UTRs. RBM47 altered splicing and abundance of a subset of its target mRNAs.
      Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling
      pathway inhibitor 1, inhibit tumor progression downstream of RBM47. Our work
      identifies RBM47 as an RNA-binding protein that can suppress breast cancer
      progression and demonstrates how the inactivation of a broadly targeted RNA
      chaperone enables selection of a pro-metastatic state. 

PMID- 24898758
TI  - C-OnSite (r) for intraoperative 3D control of pedicular screw positions.
AB  - BACKGROUND: Two-dimensional image guidance and navigation can help to reduce the
      number of misplaced pedicle screws, but do not completely prevent misplacement.
      This experimental, retrospective, non-inferiority study was designed to evaluate
      and compare the efficacy of a novel 3D imaging technique versus conventional
      postoperative CT-scan, for intra-operative determination of pedicle screw
      position accuracy. METHODS: The capacity of C-OnSite(r) to intraoperatively
      assess screw placement was evaluated in 28 clinical cases and 23 deliberately
      misplaced screws in a cadaver model, and compared to placement accuracy
      determined by standard CT. The position of each implant, as viewed by both
      modalities, was graded by three neurosurgeons, one orthopaedic-surgeon and one
      radiologist. The intermodal variance determined the difference between CT- and C
      OnSite(r) results for each observer, while the inter-observer variance measured
      the difference between ratings of the same modality by different observers.
      RESULTS: C-OnSite(r) successfully assessed 120/138 screws (25/28 cases). Mean
      procedural fluoroscopy time was 132 +/- 51 s, and 40 +/- 16s per C-OnSite(r)
      scan. The average inter-modality variance was ,15 % with mismatches >1 degrees 
      between C-OnSite(r) and the gold-standard imaging technique in only 2 % of the
      comparisons. Average inter-observer variances were about similar (12 % for CT and
      18 % for C-OnSite(r)), with deviations of >1 degrees  reaching 1 % for CT and 3 %
      for C-OnSite(r). Individual variances between experienced only observers differed
      even less. CONCLUSIONS: C-OnSite(r) is a feasible, reliable and intuitive means
      of intraoperatively visualizing pedicle screw positions and might render the
      majority of postoperative CTs superfluous. C-OnSite(r) might help avoid re
      operations for screw re-positioning.

PMID- 24898760
TI  - Clinical aspects of ballistic peripheral nerve injury: shrapnel versus gunshot.
AB  - OBJECTIVES: Ballistic injuries to peripheral nerves pose special challenges in
      terms of indications, timing and type of surgical intervention. The aim of the
      present work was to analyze our experience in the surgical treatment of
      peripheral nerve ballistic injuries with respect to the mechanism of injury
      (gunshot versus shrapnel), and identify common and dissimilar prognostic factors
      in both types of injury. METHODS: This study was conducted on 42 patients
      totaling 58 nerves. Twenty-two patients (32 nerves) were injured by gunshot and
      20 patients (26 nerves) by shrapnel. Median postoperative follow-up was 33 months
      (range 12 months to 14 years). RESULTS: Overall postoperative outcome appears to
      be more favorable for gunshot-wound (GSW) patients than shrapnel-injured
      patients, especially in terms of neuropathic pain relief (75 % vs. 58 %
      respectively, p < 0.05). Presence of foreign particles in shrapnel injured
      patients has a negative impact on the surgical outcome in terms of rate of pain
      improvement (28 % compared to 67 % in patients with and without foreign
      particles, respectively). Nerve graft reconstruction, rather than neurolysis,
      seems to be the more beneficial treatment for shrapnel-induced neuropathic pain
      (100 % vs. 47 % in improvement rate, respectively). Early surgical intervention
      (median 2 months after injury) significantly relieved neuropathic pain in 83 % of
      shrapnel-injured patients compared to 58 % in patients operated later.
      CONCLUSIONS: This study suggests that shrapnel injury is more destructive for
      nerve tissue than gunshot injury. Our impression is that early surgical
      intervention in shrapnel injuries and split nerve grafting (especially when small
      fragments are recognized in the nerve) significantly improve the patient's
      functional activity and quality of life.

PMID- 24898761
TI  - Frameless image-guided stereotactic brain biopsies: emphasis on diagnostic yield.
AB  - BACKGROUND: Studies regarding frameless stereotactic brain biopsy mainly report
      high diagnostic yield (DY) as opposed to relatively low diagnostic accuracy. This
      discrepancy raises the question of the certainty and precision of obtained
      diagnoses. This article proposes a DY definition encompassing diagnostic
      certainty and precision according to the World Health Organization (WHO) central
      nervous system (CNS) tumour classification system. Furthermore, our eight-year
      experience with this procedure is reviewed and evaluated. METHODS: A consecutive
      series of 235 frameless biopsy procedures was reviewed. Criteria were set up for
      categorising obtained diagnoses. All cases were included in a predictive factor
      analysis of inconclusive biopsy and postoperative complications. RESULTS:
      According to our predefined DY criteria, the DY was 72.8 %. The inconclusive
      biopsy outcome measured 21.7 %; the non-diagnostic biopsy outcome was 5.5 %. The
      only predictive factor found for inconclusive biopsy procedures was age under 30.
      Predictive factors for postoperative complications, which were found
      statistically significant after multivariable analysis, were glucose level and
      intra-operative haemorrhage. The total morbidity rate was 8.5 %, including a
      mortality rate of 0.9 %. CONCLUSIONS: Although frameless stereotactic brain
      biopsy procedures are considered to be relatively safe, the true DY is
      significantly less than previously reported, most probably due to the lack of
      standardised DY criteria. Based on our DY definition and subsequent DY findings,
      standardisation of DY criteria and definition is paramount for biopsy diagnosis
      interpretation.

PMID- 24898762
TI  - A normative study of the Children's Color Trails Test (CCTT) in the Cypriot
      population.
AB  - BACKGROUND: The Children's Color Trails Test (CCTT) is a neuropsychological test
      that measures attention, divided attention, and speed of mental processing. It
      has been increasingly used in the assessment of children in cross-cultural
      environments for neurological and psychiatric disorders such as seizures and
      closed head injuries, learning and/or language disabilities, attention
      deficit/hyperactivity disorder, children with manganese exposure, and children
      diagnosed with HIV virus. However, there is a paucity of studies presenting
      normative data. The aim of the present study was to provide normative data for
      the CCTT in the Cypriot population. METHODS: A total of 709 native Cypriot
      children aged 7-16 years, recruited from various public schools across the
      island, took part in the study. Exclusion criteria involved the existence of
      neurological, psychiatric, cardiological, and metabolic diseases, premature
      birth, history of maternal alcohol and drug abuse during pregnancy, low birth
      weight, hearing loss, visual problems, native language other than Greek, and
      abnormality in fine-motor movements. RESULTS: Age and gender were found to be
      important factors for the interpretation of scores in all CCTT variables. Older
      children required less time and exhibited fewer errors, near misses, and prompts
      compared to younger children. There was a consistent pattern of a 3-4 seconds
      improvement (less time in seconds) in the CCTT completion time as age increased.
      CONCLUSIONS: CCTT is a promising tool for the measurement of attention in the
      native Cypriot population. Further research is needed in children diagnosed with
      various neurological and psychiatric diseases in order to estimate validity of
      the CCTT in clinical populations.

PMID- 24898763
TI  - Nanoparticle impacts reveal magnetic field induced agglomeration and reduced
      dissolution rates.
AB  - Superparamagnetic nanoparticles (NPs) are used in a variety of magnetic field
      assisted chemical and medical applications, yet little of their fate during
      magnetic field interrogation is known. Here, fundamental and new insights in this
      are gained by cathodic particle coulometry. This methodology is used to study
      individual Fe3O4 NPs in the presence and absence of a magnetic field. It is first
      noticed that no major NP agglomeration occurs in the absence of a magnetic field
      even in a suspension of high ionic strength. In contrast, a significant magnetic
      field-induced agglomeration of NPs is observed in a magnetic field. A second new
      finding is that the dissolution of Fe3O4 NPs is strongly inhibited in a magnetic
      field. This is explained as a result of the magnetic field gradient force
      trapping the released Fe(2+) ions near the surface of a magnetized Fe3O4 NP and
      thus hindering the mass-transport controlled NP dissolution. Consequently,
      fundamental magnetic field effects are measured and quantified on both the single
      NP scale and in suspension and two novel effects are discovered. 

PMID- 24898764
TI  - mRNA sequencing of novel cell lines from human papillomavirus type-16 related
      vulval intraepithelial neoplasia: consequences of expression of HPV16 E4 and E5.
AB  - Vulval intraepithelial neoplasia is a precursor of vulval cancer and is commonly
      caused by infection with Human Papillomavirus (HPV). Development of topical
      treatments for vulval intraepithelial neoplasia requires appropriate in vitro
      models. This study evaluated the feasibility of primary culture of vulval
      intraepithelial neoplasia biopsy tissue to produce cell lines for use as in vitro
      models. A potentially immortal cell line was produced which gave rise to three
      monoclonal lines. These lines were characterized for HPV genomic integration and
      for viral gene expression using ligation-mediated PCR and quantitative PCR.
      Distinct patterns of viral integration and gene expression were observed among
      the three lines. Integration and expression data were validated using deep
      sequencing of mRNA. Gene ontology analyses of these data also demonstrated that
      expression of the HPV16 E4 and E5 proteins resulted in substantial changes in the
      composition of the cell membrane and extracellular space, associated with
      alterations in cell adhesion and differentiation. These data illustrate the
      diverse patterns of HPV gene expression potentially present within a single
      lesion. The derived cell lines provide useful models to investigate the biology
      of vulval intraepithelial neoplasia and the interactions between different HPV
      gene products and potential therapeutic agents.

PMID- 24898765
TI  - Informed consent for anesthesia: a review of practice and strategies for
      optimizing the consent process.
AB  - PURPOSE: Patients must receive information in a manner that promotes
      understanding so they can make informed decisions about anesthesia and other
      medical interventions. Unfortunately, history is replete with examples of the
      negative consequences of inadequate disclosure of information and lack of patient
      understanding. While obtaining consent for anesthesia poses unique challenges,
      the ability of the anesthesiologist to engage the patient in meaningful
      discussion is critical as a means to ensure that the patient is truly informed.
      This narrative review aims to: 1) discuss the process of informed consent as it
      applies to anesthesia practice; 2) describe the salient issues related to patient
      capacity, disclosure, understanding, decision-making, and documentation of the
      informed consent process; and 3) discuss current strategies to improve the
      presentation and understanding of consent information. SOURCE: Review of the
      extant literature, including the authors' own research. PRINCIPAL FINDINGS:
      Despite the ethical imperative of informed consent, many decision-makers have
      limited understanding of medical information. The reasons for this are
      multifactorial but often result from incomplete disclosure and presentation of
      generic information that does not take into account differences in information
      needs, values, and preferences of individual patients. Several simple strategies
      are available, however, that can enhance decision-makers' understanding of both
      written and verbal information. CONCLUSIONS: Despite the unique challenges of
      obtaining consent for anesthesia on the day of surgery, attention to the manner
      in which information for anesthesia care is provided and adoption of simple
      strategies to enhance understanding can go a long way to ensure that decision
      makers are appropriately informed.

PMID- 24898766
TI  - Overproduction of stomatal lineage cells in Arabidopsis mutants defective in
      active DNA demethylation.
AB  - DNA methylation is a reversible epigenetic mark regulating genome stability and
      function in many eukaryotes. In Arabidopsis, active DNA demethylation depends on
      the function of the ROS1 subfamily of genes that encode 5-methylcytosine DNA
      glycosylases/lyases. ROS1-mediated DNA demethylation plays a critical role in the
      regulation of transgenes, transposable elements and some endogenous genes;
      however, there have been no reports of clear developmental phenotypes in ros1
      mutant plants. Here we report that, in the ros1 mutant, the promoter region of
      the peptide ligand gene EPF2 is hypermethylated, which greatly reduces EPF2
      expression and thereby leads to a phenotype of overproduction of stomatal lineage
      cells. EPF2 gene expression in ros1 is restored and the defective epidermal cell
      patterning is suppressed by mutations in genes in the RNA-directed DNA
      methylation pathway. Our results show that active DNA demethylation combats the
      activity of RNA-directed DNA methylation to influence the initiation of stomatal
      lineage cells. 

PMID- 24898770
TI  - Design of leaving groups in radical C-C fragmentations: through-bond 2c-3e
      interactions in self-terminating radical cascades.
AB  - Radical cascades terminated by beta-scission of exocyclic C?C bonds allow for the
      formation of aromatic products. Whereas beta-scission is common for weaker bonds,
      achieving this reactivity for carbon-carbon bonds requires careful design of
      radical leaving groups. It has now been found that the energetic penalty for
      breaking a strong sigma-bond can be compensated by the gain of aromaticity in the
      product and by the stabilizing two-center, three-electron "half-bond" present in
      the radical fragment. Furthermore, through-bond communication of a radical and a
      lone pair accelerates the fragmentation by selectively stabilizing the transition
      state. The stereoelectronic design of radical leaving groups leads to a new,
      convenient route to Sn-functionalized aromatics. 

PMID- 24898769
TI  - B cells facilitate platelet production mediated by cytokines in patients with
      essential thrombocythaemia.
AB  - We investigated the role of activated B cells in thrombopoiesis through the
      production of interleukin (IL)-1beta and IL-6 in patients with essential
      thrombocythaemia. The number of B cells did not differ between essential
      thrombocythaemia patients, irrespective of the presence of Janus activated kinase
      2 V617F mutation or wild type, and age-matched healthy adults. However, the
      number of IL-1beta/IL-6-producing B cells was significantly higher in essential
      thrombocythaemia patients than that in healthy controls. The relatively high
      level of IL-1beta/IL-6 production by B cells was associated with serum B cell
      activating factor and expression of Toll-like receptor 4 on B cells. A high level
      of B cell-activating factor was present in essential thrombocythaemia patients
      with both Janus activated kinase-2 genotypes. Incubation with B cell-activating
      factor enhanced the expression of Toll-like receptor 4 on B cells. IL-1beta and
      IL-6 production was not stimulated by B cell-activating factor alone; Toll-like
      receptor 4 was activated by lipopolysaccharide or patients' sera to produce IL
      1beta and IL-6 in B cells. Moreover, essential thrombocythaemia patient B cells
      facilitated megakaryocyte differentiation when co-cultured with CD34+
      haematopoietic stem cells. Antibody neutralisation of IL-1beta and IL-6
      attenuated megakaryocyte differentiation. These data suggest that B cells play a
      crucial role in thrombopoiesis in essential thrombocythaemia patients. 

PMID- 24898768
TI  - Exploring health-related quality of life in eating disorders by a cross-sectional
      study and a comprehensive review.
AB  - BACKGROUND: People with eating disorders (ED) often report poor health-related
      quality of life (HRQoL), which is explicitly correlated to illness' severity and
      its effects on cognitive performance. We aimed to analyze health-related quality
      of life (HRQoL) in subgroups of eating disorder (ED) patients by using the brief
      version of WHOQoL questionnaire (WHOQoL-BREF) before treatment administration.
      Moreover, in order to compare our findings with other published data, we carried
      out a comprehensive review of the literature on HRQoL in ED patients. METHODS:
      Our review was carried out by means of an accurate data mining of PsychInfo and
      Medline databases and other available sources. In our cross-sectional study,
      eighty female ED patients (26 with bulimia nervosa, 33 with anorexia nervosa, 7
      with binge eating disorder and 14 with ED not otherwise specified) completed the
      WHOQoL-BREF. HRQoL scores were compared among ED subgroups and clinical
      information (presence of previous contacts, length of illness, psychiatric
      comorbidity) was considered in the analysis. RESULTS: Our review shows that with
      few exceptions ED patients have a poorer HRQoL than the healthy population of
      control and sometimes the mental component of HRQoL is the most involved
      dimension. Moreover, there are no differences in the HRQoL among ED groups, even
      if AN patients in some studies have a lower HRQoL scores. Furthermore, BED
      patients have a poorer HRQoL than obese patients who do not have binge episodes.
      Finally, all treatments were positively correlated with an improvement on general
      and specific QoL dimensions. In our sample, ED subgroups differed only for
      Psychological Health HRQoL scores (F = 4.072, df = 3; p = 0.01). No differences
      were found between inpatients and outpatients, treatment naive and previously
      treated patients and patients with or without psychiatric comorbidity. Moreover,
      HRQoL scores were not correlated to length of illness within each ED subgroup.
      CONCLUSIONS: The analysis of the literature adds some relevant information on
      HRQoL in ED and may address the future research toward the exploration of
      specific questions. One of these may be the prominent role of Psychological
      Health domain in HRQoL, since our study confirms that this component is able to
      differentiate eating disorders.

PMID- 24898771
TI  - Mediating effects of forgiveness and emotion-focused coping on post-traumatic
      stress disorder symptoms caused by physical injury and perceived threat.
AB  - INTRODUCTION: The purpose of this study was to develop and test a model
      (including cognitive appraisal, coping strategy, and forgiveness variables)
      predicting post-traumatic stress disorder (PTSD) in 127 adults who were involved
      in traffic accidents. METHODS: Participants were recruited from the inpatient and
      outpatient departments of three urban hospitals in South Korea. We utilized the
      path analysis to identify the best fitting model to our data. RESULTS: Path
      analysis showed that the baseline model compared with an alternative model was
      more appropriate for our data. Our results indicated that the severity of
      physical injury was directly related to the participants' perceived threat. The
      perceived threat had direct and indirect effects on PTSD symptoms through
      forgiveness and emotion-focused coping strategies. One of the significant
      findings was that victims' forgiveness of the person at fault for the accident
      reduced their PTSD symptoms. The severity of physical injury was not related
      directly to PTSD symptoms. DISCUSSION: Our study demonstrates that victim's
      forgiveness of the person at fault in a traumatic situation can be useful in
      helping their recovery after trauma and the forgiveness process may be applied to
      traffic accident situations as well as other types of interpersonal trauma.

PMID- 24898773
TI  - Comparative analysis of fresh and dry preserved amniotic membrane transplantation
      in partial limbal stem cell deficiency.
AB  - To compare the role of fresh and dry preserved amniotic membrane transplantation
      (AMT) in partial limbal stem cell deficiency (LSCD). 30 Patients of partial LSCD
      involving <180 degrees  of cornea of different age group were divided into 2
      groups; group A and B. Clinical diagnosis was made on the basis of presence of
      conjunctival pannus over cornea and loss of limbal palisades of Vogt. After
      taking impression cytology from the corneal surface, group A patients underwent
      conjunctival pannus resection followed by fresh AMT while group B patients
      underwent dry preserved AMT after resection of pannus. Resected specimens were
      sent for histopathological confirmation of the conjunctival tissue. Serial follow
      ups were done at 1, 2, 4, 8, 12 and 24 weeks interval post-operatively. Pre
      operative impression cytology revealed goblet cells in 40 and 53.33 % cases of
      group A and group B respectively. However, histopathological examination
      confirmed the presence of conjunctival tissue in all cases. All cases in both the
      groups maintained stable corneal epithelial surface with amelioration of clinical
      symptoms except for 1 case in group A. At the end of 24 weeks improvement in
      visual acuity was observed in 40 % cases in both the groups which was not more
      than 2 Snellen's line in any case. Complete regression of superficial
      vascularisation was observed in 60 and 53.33 % cases in group A and B
      respectively while deep vascularisation persisted in all at the end of study
      period. Recurrence of conjunctival pannus at the same site was observed in 13.33
      % in both the groups. One patient (6.66 %) developed post-operative infectious
      keratitis in group A while no major complications were observed in group B. Both
      fresh and dry AMT is equally effective in the treatment of partial LSCD. However,
      the utility of AMT is limited in corneas with long standing tissue scarring and
      vascularisation secondary to partial LSCD.

PMID- 24898772
TI  - Effects of shear stress pattern and magnitude on mesenchymal transformation and
      invasion of aortic valve endothelial cells.
AB  - Understanding the role of mechanical forces on cell behavior is critical for
      tissue engineering, regenerative medicine, and disease initiation studies.
      Current hemodynamic bioreactors are largely limited to 2D substrates or the
      application of general flow conditions at a tissue level, which eliminates the
      investigation of some essential physiological and pathological responses. One
      example is the mesenchymal transformation of endothelial cells in response to
      shear stress. Endothelial to mesenchymal transformation (EndMT) is a valve
      morphogenic mechanism associated with aortic valve disease initiation. The aortic
      valve experiences oscillatory shear on the disease-susceptible fibrosa, and the
      role of hemodynamics on adult EndMT is unknown. The goal of this work was to
      develop and characterize a microfluidic bioreactor that applies physiologically
      relevant laminar or oscillatory shear stresses to endothelial cells and permits
      the quantitative analysis of 3D cell-extracellular matrix (ECM) interactions. In
      this study, porcine aortic valve endothelial cells were seeded onto 3D collagen I
      gels and exposed to different magnitudes of steady or oscillatory shear stress
      for 48 h. Cells elongated and aligned perpendicular to laminar, but not
      oscillatory shear. Low steady shear stress (2 dyne/cm(2) ) and oscillatory shear
      stress upregulated EndMT (ACTA2, Snail, TGFB1) and inflammation (ICAM1, NFKB1)
      related gene expression, EndMT-related (alphaSMA) protein expression, and matrix
      invasion when compared with static controls or cells exposed to high steady shear
      (10 and 20 dyne/cm(2) ). Our system enables direct testing of the role of shear
      stress on endothelial cell mesenchymal transformation in a dynamic, 3D
      environment and shows that hemodynamics regulate EndMT in adult valve endothelial
      cells.

PMID- 24898775
TI  - Pyoderma gangrenosum: a possible cutaneous complication of levamisole-tainted
      cocaine abuse.

PMID- 24898774
TI  - Incidence and risk factors for retinopathy of prematurity in extreme low birth
      weight Chinese infants.
AB  - The objective of this study is to determine the incidence and risk factors of
      retinopathy of prematurity (ROP) in extremely low birth weight (ELBW) Chinese
      infants. A retrospective medical record review of all ELBW (<=1,000 g) neonates
      screened for ROP from 2007 to 2012 was performed in Hong Kong. ROP screening was
      conducted at 2 neonatal intensive care units by 3 pediatric ophthalmologists
      using the Royal College of Ophthalmologists ROP guideline and the International
      Classification of ROP. Maternal and neonatal covariates were analyzed using
      univariate and multivariate regression analyses for both ROP and Type 1 ROP. In
      131 ELBW Chinese infants, the mean gestational age (GA) and birth weight (BW)
      were 27.3 +/- 3.3 weeks and 806.9 +/- 133.7 g, respectively. The incidence of ROP
      and Type 1 ROP was 53.4 and 14.5 %, respectively. For ROP, a lighter BW, smaller
      GA, vaginal delivery, postnatal hypotension, inotrope use, bronchopulmonary
      dysplasia, surfactant use, invasive mechanical ventilation, and supplementary
      oxygen were independent risk factors for ROP, while PET was protective (P <=
      0.02). On multivariate analysis, a smaller GA was a risk factor, while PET and
      congenital heart disease were protective for ROP development (P <= 0.01). For
      Type 1 ROP, a lighter BW, smaller GA, surfactant use, and invasive mechanical
      ventilation were independent risk factors for ROP, while PET was protective (P <=
      0.02). There were no significant covariates on multivariate analysis for Type 1
      ROP. In ELBW, preterm Chinese infants, a smaller GA was a risk factor for ROP,
      while PET and congenital heart disease were protective for ROP development in
      multivariate analysis.

PMID- 24898776
TI  - Facile synthesis of Au-Pd core-shell nanocrystals with systematic shape evolution
      and tunable size for plasmonic property examination.
AB  - A facile synthetic method has been developed for the formation of Au-Pd core
      shell nanocrystals in aqueous solution in just 0.5-2 h at 50  degrees C with
      systematic shape evolution from cubic to truncated cubic, cuboctahedral,
      truncated octahedral, and octahedral structures using octahedral gold cores. By
      adjusting the amounts of H2PdCl4, ascorbic acid, and sometimes surfactants and
      gold cores added, the particle morphology can be finely tuned, and Pd shells with
      ultrathin thicknesses have been achieved. Gold cores of three different sizes
      (35, 45, and 74 nm in opposite corner distance) were used to obtain a full range
      of particle sizes and shapes for a most complete examination of their plasmonic
      properties. Visual observations made during particle synthesis reveal that Au-Pd
      cubes are formed at a faster rate than that for the growth of octahedra. For the
      smaller cubes, cuboctahedra, and truncated octahedra prepared using 35 and 45 nm
      gold cores, the surface plasmon resonance (SPR) absorption band from the gold
      cores can be seen only when the Pd shell thickness is just 1 nm at the thinnest
      points of the particles. For small-sized Au-Pd octahedra, this band is observable
      at a Pd shell thickness of around 5 nm. For larger Au-Pd nanocrystals synthesized
      from 74 nm gold cores, the Au SPR band is more recognizable for all particle
      shapes, although octahedra still exhibit the most obvious band. The band shifts
      slightly to the red going from cubes to octahedra. Simulation spectra have been
      performed, and they roughly match with the experimental spectra. Au-Pd octahedra
      with two different core sizes and shell thicknesses have been used for hydrogen
      sensing by comparing their UV-vis spectra before and after hydrogen incorporation
      forming PdH. The results show that the shell thickness is more important in
      producing a larger spectral red-shift after hydrogen absorption. 

PMID- 24898777
TI  - Lung function of preterm infants before and after viral infections.
AB  - Our aim was to determine whether viral lower respiratory tract infections (LRTIs)
      adversely affect prematurely born infants' lung function at follow up. Seventy
      infants, median gestational age 34 (range, 24-35) weeks were prospectively
      followed; 32 had an RSV (n = 14) or another respiratory viral (n = 18) LRTI
      (viral LRTI group) and 38 had no LRTI (no LRTI group). Six of the viral LRTI and
      five of the no LRTI group had been hospitalised. Nasopharyngeal aspirates (NPAs)
      obtained whenever the infants had an LRTI. Lung function (functional residual
      capacity [FRCHe], compliance [Crs] and resistance [Rrs] of the respiratory
      system) was measured at 36 weeks postmenstrual age (PMA) and 1 year corrected. At
      1 year, lung volume (FRCpleth) and airways resistance (Raw) were also assessed.
      There were no significant differences in the lung function of the two groups at
      36 weeks PMA but at 1 year, the viral LRTI compared to the no LRTI group had a
      higher mean Raw (23 versus 17 cm H2O/l/s, p = 0.0068), the differences remained
      significant after adjustment. CONCLUSION: These results suggest viral LRTIs,
      regardless of whether hospitalisation is required, adversely affect prematurely
      born infants' airway resistance at follow up.

PMID- 24898778
TI  - Serial N-terminal pro-brain natriuretic peptide measurement as a predictor of
      significant patent ductus arteriosus in preterm infants beyond the first week of
      life.
AB  - The aim of the study was to assess the role of plasma N-terminal pro-brain
      natriuretic peptide (NT-proBNP) concentration as a predictor of patent ductus
      arteriosus (PDA) in very low birth weight infants beyond the first week of life.
      This was a prospective observational study; newborns with a birth weight < 1500 g
      were eligible for enrolment. Enrolled infants were screened by echocardiography
      on day seven of life for the presence of a PDA. This was paired with a blood
      sample for NT-proBNP level. Echocardiography and NT-proBNP levels were repeated
      at weekly intervals. The primary outcome was correlation between PDA and NT
      proBNP level and between measurements of PDA significance and NT-proBNP. Sixty
      nine neonates were enrolled following parental consent. The mean birth weight was
      1119 +/- 257 g and mean gestational age was 28.6 +/- 2.6 weeks. Median NT-proBNP
      level on day seven was 11469 ng/l in infants with a PDA vs. 898 ng/l in infants
      without a PDA (p < 0.0001). There was a statistically significant correlation
      between PDA diameter and NT-proBNP level on day seven, day 14 and day 21.
      CONCLUSION: NT-proBNP concentration is significantly increased in infants with a
      PDA and correlates well with PDA diameter in the first three weeks of life.

PMID- 24898779
TI  - Atypical eruption but still Still's: case report and review of the literature.

PMID- 24898780
TI  - Anethole prevents hydrogen peroxide-induced apoptosis and collagen metabolism
      alterations in human skin fibroblasts.
AB  - The collagen metabolism alterations triggered by reactive oxygen species are
      involved in the development of various connective tissue diseases and skin aging.
      This study was designed to examine whether (E)-anethole possesses a protective
      effect on H2O2-induced alterations in collagen metabolism as well as whether it
      can prevent apoptosis in human skin fibroblasts. In cells treated with 300 uM
      H2O2, a decrease in collagen biosynthesis of 54% was observed. Pretreatment of
      cells with 0.5 uM anethole for 1 h completely prevented this alteration. Changes
      at the protein level positively correlated with alterations of type I collagen
      mRNA expression. We have shown that H2O2 caused increase in the activity of MMP-2
      and MMP-9 as well as that an increase in MMP-2 activity can contribute to the 8%
      decrease in the amount of collagen secreted into the medium. The most efficient
      suppression of these changes was observed in the presence of 0.5 uM of anethole.
      At 10 uM, in addition to suppression, an inhibitory effect of anethole on MMP-9
      activity was documented. Additionally, the 60% H2O2-induced decrease in cell
      viability was suppressed by 1 uM of anethole and a 4-fold increase in cell
      apoptosis was suppressed by 0.5 uM of anethole. Our results suggest that
      anethole, which is a small lipophilic and non-toxic molecule with the ability to
      prevent H2O2-induced collagen metabolism alterations and apoptosis in human skin
      fibroblasts, would prove useful in the development of effective agents in
      pharmacotherapy of oxidative stress-related skin diseases.

PMID- 24898781
TI  - Carnitine/acylcarnitine translocase and carnitine palmitoyltransferase 2 form a
      complex in the inner mitochondrial membrane.
AB  - Carnitine/acylcarnitine translocase and carnitine palmitoyltransferase 2 are
      members of the carnitine system, which are responsible of the regulation of the
      mitochondrial CoA/acyl-CoA ratio and of supplying substrates for the beta
      oxidation to mitochondria. This study, using cross-Linking reagent, Blue native
      electrophoresis and immunoprecipitation followed by detection with
      immunoblotting, shows conclusive evidence about the interaction between carnitine
      palmitoyltransferase 2 and carnitine/acylcarnitine translocase supporting the
      channeling of acylcarnitines and carnitine at level of the inner mitochondrial
      membrane. 

PMID- 24898783
TI  - Treating advanced hepatocellular carcinoma: How to get out of first gear.
AB  - Hepatocellular carcinoma is a common malignancy with a poor prognosis. Sorafenib
      is the only systemic therapy known to improve the overall survival of patients
      with advanced disease. The clinical benefit of sorafenib is modest and the
      mechanistic basis for its activity is unknown. Four phase 3 clinical trials have
      failed to improve on sorafenib in the frontline setting and no agent has been
      shown to impact outcomes after sorafenib failure. Several factors have
      contributed to this recent stall in drug development but new approaches hold
      promise and currently are being investigated. This review will focus on the
      current pipeline of experimental therapeutics for patients with advanced
      hepatocellular carcinoma and shed a light on scientific limitations that hamper
      the advancement of new therapies for this disease, and ways around it.

PMID- 24898782
TI  - The lipophilic vitamin C derivative, 6-o-palmitoylascorbate, protects human
      lymphocytes, preferentially over ascorbate, against X-ray-induced DNA damage,
      lipid peroxidation, and protein carbonylation.
AB  - The aim of this study was to investigate protective effects of the lipophilic
      vitamin C derivative, 6-o-palmitoylascorbate (PlmtVC), against X-ray radiation
      induced damages including cell death, DNA double-strand breaks (DSBs), lipid
      peroxidation, and protein carbonylation in human lymphocytes HEV0082, and the
      stability of PlmtVC under cell-cultured or cell-free condition. Irradiation with
      X-ray (1.5 Gy) diminished the cell viability and induced apoptosis, both of which
      were protected by pre-irradiational administration with PlmtVC. Gamma-H2A.X foci
      as a hallmark of DSBs were markedly enhanced in the irradiated cells. PlmtVC
      prevented X-ray-induced DSBs more appreciably than L-ascorbic acid (L-AA).
      Intracellular ROS production, lipid peroxidation, and protein carbonylation in
      HEV0082 cells were increased by X-ray at 1.5 Gy, all of which were significantly
      repressed by PlmtVC. PlmtVC also elevated endogenous reduced glutathione (GSH) in
      HEV0082 cells, and prevented X-ray-induced GSH depletion that are more
      appreciably over L-AA. Thus, PlmtVC prevents X-ray-induced cell death through its
      antioxidative activity. Stability tests showed that after being kept under
      physiological conditions (pH 7.4, 37  degrees C) for 14 days, vitamin C residual
      rates in PlmtVC solutions (62.2-82.0 %) were significantly higher than those in L
      AA solutions (20.5-28.7 %). When PlmtVC or L-AA was added to HEV0082 lymphocytes,
      intracellular vitamin C in L-AA-treated cells was not detectable after 24 h,
      whereas PlmtVC-treated cells could keep a high level of intracellular vitamin C,
      suggesting an excellent stability of PlmtVC. Thus, X-ray-induced diverse harmful
      effects could be prevented by PlmtVC, which was suggested to ensue intrinsically
      from the persistent enrichment of intracellular vitamin C, resulting in relief to
      X-ray-caused oxidative stress.

PMID- 24898784
TI  - Arbuscular mycorrhizal fungi and vermicompost to maximize the production of
      foliar biomolecules in Passiflora alata Curtis seedlings.
AB  - BACKGROUND: Arbuscular mycorrhizal fungi (AMF) are soil organisms that associate
      with plant roots and promote plant growth, increasing the concentration of
      secondary metabolites, which are molecules of interest to the pharmaceutical
      industry. Passiflora alata is a Brazilian medicinal plant that is used as a raw
      material for anxiolytic phytotherapeutic agents. The anxiolytic properties are
      related to the presence of biomolecules in the plant material, principally
      flavonoids. The objective of this study was to evaluate the effect of inoculation
      with AMF and organic fertilization on the production of soluble carbohydrates and
      total foliar proteins, phenols and flavonoids in P. alata seedlings. RESULTS:
      There was an effect of the tested treatments on the analyzed variables. Seedlings
      inoculated and cultivated in soil to which 0.15 kg vermicompost kg(-1) had been
      added showed increased growth and production of primary and secondary metabolites
      compared with treatments with lower levels of manure, which did not differ from
      those cultivated in soil with 0.2 kg vermicompost kg(-1). CONCLUSION: The
      inoculation of P. alata seedlings with Gigaspora albida is an alternative to
      maximize the production of pharmacologically important foliar biomolecules,
      especially flavonoids, with benefits that vary in accordance with the fertility
      of the soil.

PMID- 24898785
TI  - In vivo assessment of the vascular disrupting effect of M410 by DCE-MRI biomarker
      in a rabbit model of liver tumor.
AB  - The present study aimed to prospectively monitor the vascular disrupting effect
      of M410 by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in
      rabbits with VX2 liver tumors. Twenty-eight rabbits bearing VX2 tumors in the
      left lobe of the liver were established and randomly divided into treatment and
      control groups, intravenously injected with 25 mg/kg M410 or sterile saline,
      respectively. Conventional and DCE-MRI data were acquired on a 3.0-T MR unit at
      pretreatment, 4 h, 1, 4, 7 and 14 days post-treatment. Histopathological
      examinations [hematoxylin and eosin (H&E) and CD34 immunohistochemisty staining]
      were performed at each time point. The dynamic changes in tumor volume, kinetic
      DCE-MRI parameter [volume transfer constant (Ktrans)] and histological data were
      evaluated. Tumors grew slower in the M410 group 4-14 days following treatment,
      compared with rapidly growing tumors in the control group (P<0.05). At 4 h, 1 and
      4 days, Ktrans significantly decreased in the M410 group compared with that in
      the control group (P<0.05). However, Ktrans values were similar in the two groups
      for the other time points studied. The changes in DCE-MRI parameters were
      consistent with the results obtained from H&E and CD34 staining of the tumor
      tissues. DCE-MRI parameter Ktrans may be used as a non-invasive imaging biomarker
      to monitor the dynamic histological changes in tumors following treatment with
      the vascular targeting agent M410.

PMID- 24898787
TI  - The institute for clinical and translational science at UC Irvine: building an
      inquisitive environment where everything is questioned and there is no status
      quo.

PMID- 24898786
TI  - Comparison of investigation methods of heat injury in grapevine (Vitis) and
      assessment to heat tolerance in different cultivars and species.
AB  - BACKGROUND: In the context of global climate change, heat stress is becoming an
      increasingly important constraint on grapevine growth and berry quality. There is
      a need to breed new grape cultivars with heat tolerance and to design effective
      physiological defenses against heat stress. The investigation of heat injury to
      plants or tissues under high temperature is an important step in achieving these
      goals. At present, evaluation methods for heat injury include the gas exchange
      parameters of photosynthesis, membrane thermostability, chlorophyll content etc.;
      however, these methods have obvious disadvantages, such as insensitivity,
      inconvenience and delayed information. An effective and convenient method for
      investigating the heat injury of grapevine must be developed. RESULTS: In this
      study, an investigation protocol for a critical temperature (47 degrees C) and
      heat treatment time (40 min) was developed in detached grape leaves. Based on the
      results, we found that the OJIP test was superior to measuring electrolyte
      leakage or photosynthetic O2 evolution for investigating the heat injury of three
      cultivars of grapevine. Heat tolerance of 47 grape species and cultivars was
      evaluated through investigating heat injury using the OJIP test. Moreover, the
      electron transport chain (donor side, acceptor side and reaction center) of PSII
      in photosynthesis was further investigated. CONCLUSIONS: The OJIP test was a
      rapid, sensitive and convenient method for investigating heat injury in
      grapevine. An analysis of PSII function using this method indicated that the
      acceptor side was less sensitive to heat than was the donor side or the reaction
      center in grape leaves. Among the 47 taxa evaluated (cultivars, hybrids, and wild
      species), heat tolerance varied largely in each genotype group: most wild species
      and hybrids between V. labrusca and V. vinifera had relatively strong heat
      tolerance, but most cultivars from V. vinifera had relatively weak heat
      tolerance.

PMID- 24898789
TI  - Critical review of the epidemiologic literature regarding the association between
      congenital heart defects and exposure to trichloroethylene.
AB  - The most recent Integrated Risk Information System review of trichloroethylene
      (TCE; CAS# 79-01-6) has suggested that congenital heart defects (CHD) are a
      critical endpoint associated with exposure to this solvent. This conclusion was
      drawn, at least partly, from epidemiologic data, including several relatively
      recent studies. The current article critically reviews this epidemiologic
      literature, focusing on study quality and consistency. Literature searches
      uncovered approximately a dozen studies that specifically addressed associations
      between TCE and congenital malformations in eight populations. Four of these
      reported positive associations between TCE and heart defects, with significant
      relative risks as high as 5-6 in some subgroups. However, each of the positive
      studies had substantial design or analytical flaws that could easily explain the
      results, thereby limiting the conclusions that can be drawn. Five studies found
      no positive association with TCE, and several of these reported substantially
      fewer cases than expected despite similar/higher exposures compared to positive
      studies, further detracting from causal conclusions. Overall, this epidemiologic
      literature provides no substantive or consistent evidence linking TCE to CHD.

PMID- 24898788
TI  - Biomarker-driven EGFR therapy improves outcomes in patients with metastatic
      colorectal cancer.
AB  - As new data from randomized studies comparing EGFR-targeting therapies with VEGF
      inhibitors emerge, the treatment landscape for metastatic colorectal cancer is
      expected to change. Although both the VEGF inhibitor bevacizumab and the anti
      EGFR antibody cetuximab are approved in the first-line setting, they have not
      until recently been compared directly in randomized studies. Unlike targeted
      therapy in the EGFR pathway, there are no biomarkers guiding VEGF treatment.
      Recent data, discussed in this review, demonstrate that patients with KRAS/NRAS
      wild-type tumors benefit from anti-EGFR therapy in the first-line setting and
      that anti-EGFR therapy may be superior when compared with anti-VEGF approaches.
      This review focuses on the clinical utility of targeting EGFR by revisiting the
      biologic rationale for EGFR inhibition in metastatic colorectal cancer and
      providing new insight on the advancements in biomarker analyses with the
      potential to change practice. 

PMID- 24898791
TI  - Identification of a novel HLA-B*51 variant allele, B*51:59, in a Chinese Han
      individual.
AB  - HLA-B*51 differs from the closest allele B*51:06:01 by nt 956 C > T (codon 171
      CAC>TAC) missense mutation in exon 3.

PMID- 24898790
TI  - Aortic valve disease.
AB  - Aortic valve disease is common and has significant impact on prognosis and
      quality of life. In this educational review, we cover the pathophysiology,
      presentation and assessment of aortic stenosis (AS) and aortic regurgitation
      (AR), including the role of imaging modalities beyond echocardiography. We review
      current treatment strategies and emphasise the use and indications for
      transcatheter aortic valve implantation (TAVI) in view of recent data
      highlighting its emergence as a novel treatment option for patients with AS, who
      are unsuitable for conventional aortic valve replacement (AVR). We also describe
      novel surgical approaches for AR and potential future strategies for percutaneous
      intervention. 

PMID- 24898792
TI  - Unoxidized graphene/alumina nanocomposite: fracture- and wear-resistance effects
      of graphene on alumina matrix.
AB  - It is of critical importance to improve toughness, strength, and wear-resistance
      together for the development of advanced structural materials. Herein, we report
      on the synthesis of unoxidized graphene/alumina composite materials having
      enhanced toughness, strength, and wear-resistance by a low-cost and
      environmentally benign pressure-less-sintering process. The wear resistance of
      the composites was increased by one order of magnitude even under high normal
      load condition (25 N) as a result of a tribological effect of graphene along with
      enhanced fracture toughness (KIC) and flexural strength (sigmaf) of the
      composites by ~75% (5.60 MPa.m(1/2)) and ~25% (430 MPa), respectively, compared
      with those of pure Al2O3. Furthermore, we found that only a small fraction of
      ultra-thin graphene (0.25-0.5 vol%, platelet thickness of 2-5 nm) was enough to
      reinforce the composite. In contrast to unoxidized graphene, graphene oxide (G-O)
      and reduced graphene oxide (rG-O) showed little or less enhancement of fracture
      toughness due to the degraded mechanical strength of rG-O and the structural
      defects of the G-O composites. 

PMID- 24898793
TI  - Mechanisms underlying the beneficial effect of soy protein in improving the
      metabolic abnormalities in the liver and skeletal muscle of dyslipemic insulin
      resistant rats.
AB  - PURPOSE: The present study analyzes the effect of the replacement of dietary
      casein by soy protein on the mechanisms underlying dyslipidemia, liver steatosis
      and altered glucose and lipid metabolism in the skeletal muscle which developed
      in rats fed long-term a sucrose-rich diet (SRD). METHODS: Wistar rats were fed a
      SRD for 4 months. From months 4 to 8, half the animals continued with the SRD,
      and the other half were fed a SRD in which the source of protein casein was
      replaced by soy. The control group received a diet with cornstarch as source of
      carbohydrate. RESULTS: Compared to SRD-fed animals, the rats fed soy showed: A-
      in the liver: reduction of triglyceride and cholesterol storage and decreased
      steatosis; normalization of mature forms of the protein mass levels of SREBP-1
      and the activities of lipogenic enzymes, while the protein mass level of PPAR
      alpha and fatty acid oxidase activity increased. B-in the gastrocnemius muscle:
      normalization of the enhanced lipid storage and the altered glucose oxidation,
      improving glucose phosphorylation; decreasing protein mass level of nPKCtheta in
      the membrane fraction; reversion of the impaired insulin-stimulated glucose
      transporter Glut-4, and glucose-6-phosphate and glycogen concentrations. Besides,
      dyslipidemia and glucose homeostasis returned to control values. CONCLUSIONS:
      This study provides new information concerning some key mechanisms related to the
      effect of dietary soy on hepatic lipid metabolism and insulin action in the
      skeletal muscle in the presence of pre-existing dyslipidemia and insulin
      resistance induced by a SRD.

PMID- 24898794
TI  - Acetate supplementation modulates brain adenosine metabolizing enzymes and
      adenosine A2A receptor levels in rats subjected to neuroinflammation.
AB  - BACKGROUND: Acetate supplementation reduces neuroglia activation and pro
      inflammatory cytokine expression in rat models of neuroinflammation and Lyme
      neuroborreliosis. Because single-dose glyceryl triacetate (GTA) treatment
      increases brain phosphocreatine and reduces brain AMP levels, we postulate that
      GTA modulates adenosine metabolizing enzymes and receptors, which may be a
      possible mechanism to reduce neuroinflammation. METHODS: To test this hypothesis,
      we quantified the ability of GTA to alter brain levels of ecto-5'-nucleotidase
      (CD73), adenosine kinase (AK), and adenosine A2A receptor using western blot
      analysis and CD73 activity by measuring the rate of AMP hydrolysis.
      Neuroinflammation was induced by continuous bacterial lipopolysaccharide (LPS)
      infusion in the fourth ventricle of the brain for 14 and 28 days. Three treatment
      strategies were employed, one and two where rats received prophylactic GTA
      through oral gavage with LPS infusion for 14 or 28 days. In the third treatment
      regimen, an interventional strategy was used where rats were subjected to 28 days
      of neuroinflammation, and GTA treatment was started on day 14 following the start
      of the LPS infusion. RESULTS: We found that rats subjected to neuroinflammation
      for 28 days had a 28% reduction in CD73 levels and a 43% increase in AK levels
      that was reversed with prophylactic acetate supplementation. CD73 activity in
      these rats was increased by 46% with the 28-day GTA treatment compared to the
      water-treated rats. Rats subjected to neuroinflammation for 14 days showed a 50%
      increase in levels of the adenosine A2A receptor, which was prevented with
      prophylactic acetate supplementation. Interventional GTA therapy, beginning on
      day 14 following the induction of neuroinflammation, resulted in a 67% increase
      in CD73 levels and a 155% increase in adenosine A2A receptor levels. CONCLUSION:
      These results support the hypothesis that acetate supplementation can modulate
      brain CD73, AK and adenosine A2A receptor levels, and possibly influence
      purinergic signaling.

PMID- 24898797
TI  - Fundamental challenges in packing problems: from spherical to non-spherical
      particles.
AB  - Random packings of objects of a particular shape are ubiquitous in science and
      engineering. However, such jammed matter states have eluded any systematic
      theoretical treatment due to the strong positional and orientational correlations
      involved. In recent years progress on a fundamental description of jammed matter
      could be made by starting from a constant volume ensemble in the spirit of
      conventional statistical mechanics. Recent work has shown that this approach,
      first introduced by S. F. Edwards more than two decades ago, can be cast into a
      predictive framework to calculate the packing fractions of both spherical and non
      spherical particles. 

PMID- 24898795
TI  - Relationship between multiple water swallows and gastroesophageal reflux in
      patients with normal esophageal motility.
AB  - Multiple water swallows (MWS) stimulates neural inhibition, resulting in
      abolition of contractions in the esophageal body and complete lower esophageal
      sphincter relaxation, which is followed by peristalsis and the lower esophageal
      sphincter contraction. We assessed the relationship between MWS and
      gastroesophageal reflux in patients with esophageal symptoms and with normal
      findings by high-resolution manometry (HRM). We retrospectively reviewed the
      clinical records of patients who underwent HRM and a 24-hour ambulatory impedance
      pH study. Correlation between the findings of the impedance-pH study and abnormal
      MWS responses without motility disorders was evaluated. Independent t-tests were
      used for statistical analysis. Of 28 patients, 20 (71%) had abnormal MWS
      responses: four (20%) had abnormal responses during MWS, six (30%) had abnormal
      responses after MWS, and 10 (50%) had abnormal responses both during and after
      MWS. Total acid exposure times were significantly longer in patients with
      abnormal MWS responses than in patients with normal MWS responses. In particular,
      upright acid exposure time and all reflux percent times were significantly longer
      in patients with abnormal MWS responses. However, bolus clearance time and
      longest reflux episode were not different between the two groups. Abnormal MWS
      responses predicted increased acid exposure times in patients with normal
      findings of HRM by the Chicago classification. 

PMID- 24898798
TI  - Soil heavy metal contamination and risk assessment around the Fenhe Reservoir,
      China.
AB  - Heavy metal contamination in the soil around a water source is a particularly
      serious issue, because these heavy metals can be transferred into the water
      source and can pose significant human health risks through the contamination of
      drinking water or farmland irrigation water. In this paper, we collected surface
      soil samples from the area surrounding the Fenhe Reservoir. The concentrations of
      As, Cd, Cr, Cu, Hg, Ni, and Zn were determined and the potential ecological risks
      posed by the heavy metals were quantitatively evaluated. The primary inputs for
      As, Ni, and Zn were natural sources, whereas the other elements were derived from
      mainly anthropogenic sources. Hg displays more serious environmental impacts than
      the other heavy metals. The upper reaches of the reservoir, located in the
      northwest, display a higher potential ecological risk. 

PMID- 24898796
TI  - Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface
      display on Salmonella.
AB  - BACKGROUND: Autotransporter proteins represent a treasure trove for molecular
      engineers who modify Gram-negative bacteria for the export or secretion of
      foreign proteins across two membrane barriers. A particularly promising direction
      is the development of autotransporters as antigen display or secretion systems.
      Immunologists have been using ovalbumin as a reporter antigen for years and have
      developed sophisticated tools to detect specific T cells that respond to
      ovalbumin. Although ovalbumin-expressing bacteria are being used to trace T cell
      responses to colonizing or invading pathogens, current constructs for ovalbumin
      presentation have not been optimized. RESULTS: The activation of T helper cells
      in response to ovalbumin was improved by displaying the OVA-CD4 reporter epitope
      as a multimer on the surface of Salmonella and fused to the autotransporter MisL.
      Expression was optimized by including tandem in vivo promoters and two post
      segregational killing systems for plasmid stabilization. CONCLUSIONS: The use of
      an autotransporter protein to present relevant epitope repeats on the surface of
      bacteria, combined with additional techniques favoring stable and efficient in
      vivo transcription, optimizes antigen presentation to T cells. The technique of
      multimeric epitope surface display should also benefit the development of new
      Salmonella or other enterobacterial vaccines.

PMID- 24898799
TI  - Aerobic transformation of BDE-47 by a Pseudomonas putida sp. strain TZ-1 isolated
      from PBDEs-contaminated sediment.
AB  - A bacterial isolate, TZ-1, was isolated from contaminated sediment near
      electronic waste dismantling workshops, Taizhou, China that degraded 2,2',4,4'
      tetrabrominated diphenyl ether (BDE-47). The isolate was identified as
      Pseudomonas putida sp. with respect to its morphology, biochemical
      characteristics and 16SrDNA sequence analysis. TZ-1 can use BDE-47 as the sole
      carbon and energy source for growth in mineral salt medium. The isolate degraded
      BDE-47 up to 49.96 % of the initially applied concentration of 50 MUg L(-1) after
      7 days of incubation at 150 rpm, 30 degrees C. Static conditions with pH 6.5 and
      temperature 30 degrees C were considered to be optimum for BDE-47 biodegradation.
      Addition of co-substrates promoted cell growth, but decreased the degradation
      rate for BDE-47.

PMID- 24898800
TI  - Combined effects of Iranian heavy crude oil and bacterial challenge
      (Streptococcus iniae) on biotransformation and innate immune responses in
      rockfish (Sebastes schlegeli).
AB  - To clarify the effects of spilled crude oil on fish bacterial disease resistance,
      rockfish (Sebastes schlegeli) were exposed to Iranian Heavy crude oil (IHCO) and
      Streptomyces iniae in combination. Hepatic biotransformation enzymes
      (ethoxyresorufin O-de-ethylase, glutathione-S-transferase) and plasma biochemical
      parameters (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and
      glucose) in fish exposed to IHCO were not significantly different from those in
      unexposed fish. The level of biliary 1-OH-pyrene and cytochrome P4501A mRNA
      expression increased in a dose-dependent manner with IHCO exposure. The
      interferon stimulated gene 15, interleukin-1beta and cathepsin L were increased
      significantly in the liver in IHCO-exposed fish, but not dose-dependently, but
      the granulocyte colony stimulating factor was not related to IHCO exposure. The
      percentage mortality in fish following a single exposure to S. iniae was
      positively correlated with IHCO exposure concentration. We concluded that IHCO
      exposure exacerbates fish mortality following environmental bacterial infection. 

PMID- 24898802
TI  - Evaluating the prevention of premature cessation of exclusive breastfeeding in
      the general practice setting during the scheduled child immunisation
      consultation: a pilot study.
AB  - The purpose of this study was to test and evaluate the feasibility and clinical
      acceptability of the use of an infant feeding data collection tool during the
      scheduled childhood immunisation consultation, and to explore the appropriateness
      of this consultation as a site for a future intervention aiming to increase
      exclusive breastfeeding through the provision of advice and support to mothers.
      This descriptive exploratory (quantitative and qualitative) study used purposeful
      sampling to enrol five general practices in Hobart, Tasmania. General
      practitioners (GPs) and practice nurses (PNs) trialled and evaluated a paper
      based data collection tool over a 6-week period from May through to June 2011.
      Twenty-two (13 GPs; 2 GP registrars and 7 PNs) participants trialled and
      evaluated the data collection tool (n = 54). From the evaluation questionnaire,
      field notes and informal interviews (n = 7), six conceptual headings emerged:
      setting; time pressures; resources and collaboration; mothers need to talk;
      professional exclusion; and lack of collaboration. The scheduled childhood
      immunisation consultation provides an opportunity for mothers and primary health
      practitioners to talk briefly about infant feeding and for the collection of
      infant feeding data. However, the immunisation consultation is not well suited to
      a breastfeeding support intervention as it is already very busy focusing on
      immunisation issues. Consideration should be given to the evaluation of a
      dedicated general practice/primary health 'infant feeding' consultation.

PMID- 24898801
TI  - Sorafenib is tolerable and improves clinical outcomes in patients with FLT3-ITD
      acute myeloid leukemia prior to stem cell transplant and after relapse post
      transplant.

PMID- 24898803
TI  - 17beta-estradiol induces the proliferation of hematopoietic stem cells by
      promoting the osteogenic differentiation of mesenchymal stem cells.
AB  - The process of hematopoiesis is associated with hematopoietic stem cells (HSCs)
      and the hematopoietic microenvironment. Osteoblasts, derived from mesenchymal
      stem cells (MSCs), are one of the most important components in the hematopoietic
      microenvironment. Osteoblasts secrete a variety of cytokines including
      interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM
      CSF), thereby regulating the biological activities of HSCs. It has been shown
      that hematopoiesis dysfunction can be induced by estrogen-deficiency through the
      exhaustion of HSCs. However, the effect of estrogen on the proliferation of HSCs
      is not fully understood. The aim of this study was to investigate the role of
      estradiol in the process of hematopoiesis, especially regarding the proliferation
      of HSCs in vitro. Bone marrow-derived MSCs and HSCs were isolated from 3-month
      old female Sprague-Dawley rats. Mineralization ability and osteocalcin assays
      demonstrated that treatment with 17beta-estradiol (E2) significantly enhanced the
      osteogenic differentiation of MSCs. HSCs and MSCs were then cocultured with or
      without E2 treatment. Colony forming assays demonstrated that E2 increased the
      number of colony forming units-granulocyte/macrophage in a dose-dependent manner
      when HSCs were co-cultured with MSCs in Osteogenic Medium that is suitable for
      the in vitro osteogenic differentiation. Further, increased concentrations of GM
      CSF and IL-6 were detected by enzyme linked immunosorbent assay (ELISA). These
      results indicate that E2 induces the proliferation of HSCs, which depends on the
      promotion of osteogenic differentiation of MSCs, and that process is mediated by
      both GM-CSF and IL-6. 

PMID- 24898804
TI  - The anti-inflammatory impact of omega-3 polyunsaturated Fatty acids during the
      establishment of endometriosis-like lesions.
AB  - PROBLEM: The anti-inflammatory impact of three polyunsaturated fatty acids (3
      PUFA) in endometriosis is incompletely understood. The effect of 3-PUFA on
      endometriosis-like lesions is evaluated as a potential anti-inflammatory
      treatment target. METHOD OF STUDY: Wild Type (WT) and transgenic Fat-1 mice (high
      levels of endogenous 3-PUFA) were utilized in a uterine tissue transplant
      endometriosis model. Experimental donor*host pairs included: WT*WT (WW), WT*Fat-1
      (WF), and Fat-1*Fat-1 (FF). Cytokine content (IL-1beta, IL-2, IL-4, IL-6, IL-10,
      IL-12, IL-17A, IFN-gamma, TNF-gamma, MCP-1 and RANTES) and immunocellular
      composition in lesions was determined. RESULTS: Intralesion IL-6 in WF hosts was
      99-fold lower than WW hosts (P=0.03). Compared to WW host lesions, Cox-2 levels
      were decreased in WF [1.5-fold (P=0.02)] and FF [1.2-fold (P=0.01)] host lesions,
      respectively, and intralesion VEGF expression was increased [1.8-fold; P=0.02
      (WF) and 1.5-fold; P=0.01 (FF)]. Lesions in FF hosts demonstrated reduced
      phosphohistone 3 expression (70%; P=0.03) compared to WW control hosts.
      CONCLUSIONS: Systemic host 3-PUFA levels influence immune, angiogenic, and
      proliferative factors implicated in the early establishment of endometriosis.

PMID- 24898805
TI  - Effect of recombinant hPTEN gene expression on PDGF induced VSMC proliferation.
AB  - Human phosphatase and tensin homolog (hPTEN) gene was expressed in vascular
      smooth muscle cells (VSMCs) to study its effect on VSMC proliferation induced in
      platelet-derived growth factor (PDGF) conditioned medium. After G418 selection,
      MTT assay was conducted to examine transfected VSMC proliferation induced in
      human PDGF conditioned medium. We successfully constructed eukaryotic expression
      vector pcDNA4/myc-His-PTEN and transferred into VSMC cells. We report that in
      vitro proliferation of VSMC was inhibited in PTEN transfected VSMCs induced in
      PDGF conditioned medium. RT-PCR and Western blot results indicated significantly
      high levels of protein kinase B-PKB and nuclear factor kappa B mRNA and protein,
      respectively, in PDGF group as compared with the control group. 

PMID- 24898806
TI  - An association study of histological types of gastric carcinoma with Helicobacter
      pylori infection.
AB  - The aim of this study was to study the relation between histopathological
      classification of gastric carcinoma and Helicobacter pylori (H. pylori)
      infection. 200 patients with confirmed gastric carcinoma between January 2010 and
      January 2012 from our hospital were included. All these patients went through
      endoscopy and histological examinations for gastric carcinoma and immunological
      test for H. pylori infection. Patients were grouped according to the histological
      classification, and the infection rates of H. pylori in different groups were
      compared. Types of gastric cancer that was closely related to H. pylori infection
      were identified. Infection rate in patients with the intestinal type of gastric
      cancer was significantly higher compared to those with the diffuse type. For
      tubular type of carcinoma, the well to medium-differentiated group had a
      significantly higher infection rate than the poorly differentiated group.
      Helicobacter pylori infection and histological types were relevant. The effect of
      H. pylori infection on the intestinal type was more significant than that on the
      diffuse type. The infection rate of well-differentiated group was higher than
      that of the poorly differentiated group, which suggested an association between
      H. pylori infection and the degree of differentiation of tubular cancerous
      tissue. 

PMID- 24898807
TI  - Overexpression of microRNA-122 re-sensitizes 5-FU-resistant colon cancer cells to
      5-FU through the inhibition of PKM2 in vitro and in vivo.
AB  - 5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in the
      treatment of colon cancer. However, acquired chemoresistance is becoming one of
      the major challenges for patients with advanced stages of colon cancer.
      Currently, the mechanisms underlying cancer cell resistance to 5-FU are not fully
      understood. MicroRNAs (miRNA) have been suggested to play important roles in
      tumorigenesis and drug resistance in colon cancer. In this study, we generated 5
      FU-resistant colon cancer cell lines from which we found that miR-122 was
      downregulated in 5-FU-resistant cells compared with sensitive cells. Meanwhile,
      the glucose metabolism is significantly upregulated in 5-FU-resistant cells. We
      report that PKM2 is a direct target of miR-122 in colon cancer cell. Importantly,
      overexpression of miR-122 in 5-FU-resistant cells resensitizes 5-FU resistance
      through the inhibition of PKM2 both in vitro and in vivo. In summary, these
      findings reveal that the dysregulated glucose metabolism contributes to 5-FU
      resistance, and glycolysis inhibition by miR-122 might be a promising therapeutic
      strategy to overcome 5-FU resistance. 

PMID- 24898810
TI  - The head of Medusa: Peter Paul Rubens and Frans Snyders.

PMID- 24898811
TI  - Was risk of suicide underestimated?

PMID- 24898812
TI  - Selected pregnancy and delivery outcomes after exposure to antidepressant
      medication.

PMID- 24898813
TI  - Physical literacy: importance, assessment and future directions.
AB  - Physical literacy (PL) has become a major focus of physical education, physical
      activity and sports promotion worldwide. PL is a multifaceted conceptualisation
      of the skills required to fully realise potentials through embodied experience.
      Substantial financial investments in PL education by governments are underpinned
      by a wide range of anticipated benefits, including expectations of significant
      future savings to healthcare, improved physical and psychological well-being of
      the population, increased work-force productivity and raised levels of expertise
      in sport and exercise participation. However, disappointingly, scientific
      evidence showing the efficacy of PL interventions to successfully meet such high
      expectation is limited. We suggest that contradictions in research findings are
      due largely to limitations in movement assessment batteries and consequent
      discrepancies between measurements used to assess the immediate outcomes of PL
      programmes. Notably, there is no robust empirical tool for evidencing skill
      learning in the physical movement component of PL, education and this presents a
      serious limitation to the design of, and claims that can be made for, such
      interventions. Considering the parameters of proficient PL skills and the
      limitations of current evaluation instruments, possible future directions for
      developing empirical measures of PL movement skills are presented. 

PMID- 24898815
TI  - Diet-induced hypoxia responsive element demethylation increases CEACAM6
      expression, favouring Crohn's disease-associated Escherichia coli colonisation.
AB  - OBJECTIVE: Adherent-invasive Escherichia coli (AIEC) are abnormally predominant
      on Crohn's disease (CD) ileal mucosa. AIEC strains adhere to enterocytes via
      interaction between type 1 pili and CEACAM6 receptors abnormally expressed on CD
      ileal mucosa, leading to gut inflammation. We analysed whether epigenetic
      mechanisms are involved in the upregulation of CEACAM6 expression in intestinal
      epithelial cells (IECs). DESIGN: Methylation of CEACAM6 promoter was analysed
      using bisulfite sequencing and site-specific methylation by SnapShot. pCpGfree
      reporter system was used to analyse CEACAM6 promoter activity. Transgenic mice
      expressing human CEACAM6 fed either standard food or a low-methyl diet (LMD) were
      orally challenged with 10(9) AIEC LF82. After 3 days, gut-associated AIEC and
      proinflammatory cytokines were quantified. RESULTS: Analysis of CEACAM6 gene
      promoter revealed potentially methylated dinucleotide CpGs within HIF-1
      responsive elements (HREs). Methylation levels of CpG within CEACAM6 promoter
      were inversely correlated with CEACAM6 expression in IEC expressing various
      levels of CEACAM6. We show the critical role of HRE methylation and transcription
      factor HIF-1 in the regulation of CEACAM6 gene in IEC. This was confirmed in
      transgenic mice expressing human CEACAM6 fed a LMD. LMD-dependent HRE
      demethylation led to abnormal gut expression of CEACAM6, favouring AIEC
      colonisation and subsequent inflammation. CONCLUSIONS: HRE hypomethylation in
      CEACAM6 promoter correlates with high expression in IEC. Our findings suggest
      that abnormal DNA methylation leading to CEACAM6 increased expression and AIEC
      mediated gut inflammation can be related to changes in nutritional habits, such
      as low intake in methyl donor molecules, leading to abnormal epigenetic marks in
      mouse model mimicking CD susceptibility.

PMID- 24898817
TI  - Experimental and theoretical studies of H2O oxidation by neutral Ti2O4,5 clusters
      under visible light irradiation.
AB  - A new photo excitation fast flow reactor system is constructed and used to
      investigate reactions of neutral TimOn clusters with H2O under visible (532 nm)
      light irradiation. Single photon ionization at 118 nm (10.5 eV) is used to detect
      neutral cluster distributions through time of flight mass spectrometry. TimOn
      clusters are generated through laser ablation of a titanium target in the
      presence of 4% O2/He carrier gas. Association products Ti2O4(H2O) and Ti2O5(H2O)
      are observed for reactions of H2O and TimOn clusters without irradiation. Under
      532 nm visible light irradiation of the fast flow reactor, only the Ti2O5(H2O)
      feature disappears. This light activated reaction suggests that visible radiation
      can induce chemistry for Ti2O5(H2O), but not for Ti2O4(H2O). Density functional
      theory (DFT) and time-dependent (TD) DFT calculations are performed to explore
      the ground and first excited state potential energy surfaces (PES) for the
      reaction Ti2O5 + H2O -> Ti2O4 + H2O2. A high barrier (1.33 eV) and a
      thermodynamically unfavorable (1.14 eV) pathway are obtained on the ground state
      PES for the Ti2O5 + H2O reaction; the reaction is also thermodynamically
      unfavorable (1.54 eV) on the first singlet excited state PES. The reaction is
      proposed to occur on the ground state PES through a conical intersection
      ((S1/S0)CI), and to generate products Ti2O4 and H2O2 on the ground state PES.
      This mechanism is substantiated by a multi-reference ab initio calculation at the
      complete active space self-consistent field (CASSCF) level. The S0-S1 vertical
      excitation energy of Ti2O4 (3.66 eV) is much higher than the 532 nm photon energy
      (2.33 eV), suggesting this visible light driven reaction is unfavorable for the
      Ti2O4 cluster. The TDDFT calculated optical absorption spectra of Ti2O4 and Ti2O5
      further indicate that Ti2O5 like structures on a titanium oxide surface are the
      active catalytic sites for visible light photo-catalytic oxidation of water. 

PMID- 24898814
TI  - Achilles tendon injury risk factors associated with running.
AB  - BACKGROUND: Research into the nature of overuse Achilles tendon injuries is
      extensive, yet uncertainty remains around how to identify athletes susceptible to
      Achilles tendon injury. OBJECTIVE: To identify the strength of evidence for
      biomechanical risk factors associated with Achilles tendon injuries. RESEARCH
      METHODS: SPORTDiscus, CINAHL, Web of Science and PubMed were searched for
      Achilles tendon injury risk factors and biomechanical measures which are altered
      in runners with Achilles tendon injuries, excluding ruptures. Fifteen articles
      were included in the analysis. RESULTS: Two variables, high vertical forces and
      high arch, showed strong evidence for reduced injury risk. High propulsive forces
      and running on stiffer surfaces may also be protective. Only one biomechanical
      variable, high braking force, showed clear evidence for increasing Achilles
      injury risk. DISCUSSION: Gait retraining to direct the centre of mass further
      forward to reduce high braking force could be useful in decreasing the risk of
      Achilles injury. The majority of biomechanical risk factors examined showed
      unclear results, which is likely due to the multifactorial nature of Achilles
      overuse injuries. Many risk factors are related to how the athlete's body
      interacts with the environment during gait, including ground reaction forces,
      muscle activity both prior to landing and immediately post ground contact, and
      joint motion throughout stance. CONCLUSION: Multiple risk factors have been
      associated with the development of Achilles tendon injuries in running athletes
      but most effects remain unclear. Advice for athletes recovering from Achilles
      tendon injuries could include avoiding soft surfaces and reducing the pace of
      recovery runs. Orthotic intervention could assist athletes with low arches but
      modification of pronation should be viewed with caution. Strength training and
      gait retraining could be beneficial for reducing injury risk.

PMID- 24898816
TI  - The upper respiratory pyramid: early factors and later treatment utilization in
      World Trade Center exposed firefighters.
AB  - BACKGROUND: We investigated early post 9/11 factors that could predict
      rhinosinusitis healthcare utilization costs up to 11 years later in 8,079 World
      Trade Center-exposed rescue/recovery workers. METHODS: We used bivariate and
      multivariate analytic techniques to investigate utilization outcomes; we also
      used a pyramid framework to describe rhinosinusitis healthcare groups at early
      (by 9/11/2005) and late (by 9/11/2012) time points. RESULTS: Multivariate models
      showed that pre-9/11/2005 chronic rhinosinusitis diagnoses and nasal symptoms
      predicted final year healthcare utilization outcomes more than a decade after WTC
      exposure. The relative proportion of workers on each pyramid level changed
      significantly during the study period. CONCLUSIONS: Diagnoses of chronic
      rhinosinusitis within 4 years of a major inhalation event only partially explain
      future healthcare utilization. Exposure intensity, early symptoms and other
      factors must also be considered when anticipating future healthcare needs.

PMID- 24898818
TI  - Association analysis of IGF2BP2, KCNJ11, and CDKAL1 polymorphisms with type 2
      diabetes mellitus in a Moroccan population: a case-control study and meta
      analysis.
AB  - Associations with type 2 diabetes mellitus have been identified for variants
      CDKAL1 rs7756992, KCNJ11 rs5219, and IGF2BP2 rs4402960 in different populations.
      In a case-control study of 250 unrelated Moroccan diabetic patients and 250
      healthy controls, we used TaqMan allelic discrimination assays to genotype the
      three SNPs and meta-analysis to investigate the association between the
      polymorphisms and diabetes in Arab populations. The results showed a significant
      diabetes association only with the variant rs4402960 of the IGF2BP2 gene under
      additive 2 (GG vs. TT; p = 0.009) and recessive (TT vs. GG+GT; p = 0.003) models.
      Meta-analysis indicated significant association between the IGF2BP2 rs4402960 and
      CDKAL1 rs7756992 polymorphisms and increased risk of diabetes in Arab
      populations. According to our results, the case-control study and meta-analysis
      revealed a significant association between the IGF2BP2 rs4402960 variant and type
      2 diabetes in Moroccan and Arab populations.

PMID- 24898819
TI  - Notch1 stimulation induces a vascularization switch with pericyte-like cell
      differentiation of glioblastoma stem cells.
AB  - Glioblastoma multiforms (GBMs) are highly vascularized brain tumors containing a
      subpopulation of multipotent cancer stem cells. These cells closely interact with
      endothelial cells in neurovascular niches. In this study, we have uncovered a
      close link between the Notch1 pathway and the tumoral vascularization process of
      GBM stem cells. We observed that although the Notch1 receptor was activated, the
      typical target proteins (HES5, HEY1, and HEY2) were not or barely expressed in
      two explored GBM stem cell cultures. Notch1 signaling activation by expression of
      the intracellular form (NICD) in these cells was found to reduce their growth
      rate and migration, which was accompanied by the sharp reduction in neural stem
      cell transcription factor expression (ASCL1, OLIG2, and SOX2), while HEY1/2,
      KLF9, and SNAI2 transcription factors were upregulated. Expression of OLIG2 and
      growth were restored after termination of Notch1 stimulation. Remarkably, NICD
      expression induced the expression of pericyte cell markers (NG2, PDGFRbeta, and
      alpha-smooth muscle actin [alphaSMA]) in GBM stem cells. This was paralleled with
      the induction of several angiogenesis-related factors most notably cytokines
      (heparin binding epidermal growth factor [HB-EGF], IL8, and PLGF), matrix
      metalloproteinases (MMP9), and adhesion proteins (vascular cell adhesion molecule
      1 [VCAM1], intercellular adhesion molecule 1 [ICAM1], and integrin alpha 9
      [ITGA9]). In xenotransplantation experiments, contrasting with the infiltrative
      and poorly vascularized tumors obtained with control GBM stem cells, Notch1
      stimulation resulted in poorly disseminating but highly vascularized grafts
      containing large vessels with lumen. Notch1-stimulated GBM cells expressed
      pericyte cell markers and closely associated with endothelial cells. These
      results reveal an important role for the Notch1 pathway in regulating GBM stem
      cell plasticity and angiogenic properties.

PMID- 24898822
TI  - Retinal detachment associated with posterior chamber phakic intraocular lens
      implantation.

PMID- 24898821
TI  - Enterohaemorrhagic Escherichia coli inhibits recycling endosome function and
      trafficking of surface receptors.
AB  - Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC/EHEC) manipulate
      many cell processes by injecting effector proteins from the bacteria into the
      host cell via a Type III secretion system. In this paper we report that the
      effector protein EspG disrupts recycling endosome function. In particular, we
      found that following transferrin binding and endocytosis EspG reduces recycling
      of the transferrin receptor (TfR), the prototypical recycling protein, from an
      intracellular location to the cell surface, resulting in an accumulation of TfR
      within the cell. The surface levels of three receptors [TfR, epidermal growth
      factor receptor (EGFR) and beta1 integrin] were tested and found to be reduced
      dependent on EspG translocation. Furthermore, disruption of recycling endosome
      function and the reduced surface presentation of receptors was dependent on the
      previously reported RabGAP activity and ARF binding ability of EspG. This paper
      therefore supports the previous hypothesis that EspG acts as an enzyme scaffold
      perturbing cell signalling events, in this case altering recycling endosome
      function and cell surface receptor levels during infection. 

PMID- 24898820
TI  - Microcephaly genes evolved adaptively throughout the evolution of eutherian
      mammals.
AB  - BACKGROUND: Genes associated with the neurodevelopmental disorder microcephaly
      display a strong signature of adaptive evolution in primates. Comparative data
      suggest a link between selection on some of these loci and the evolution of
      primate brain size. Whether or not either positive selection or this phenotypic
      association are unique to primates is unclear, but recent studies in cetaceans
      suggest at least two microcephaly genes evolved adaptively in other large brained
      mammalian clades. RESULTS: Here we analyse the evolution of seven microcephaly
      loci, including three recently identified loci, across 33 eutherian mammals. We
      find extensive evidence for positive selection having acted on the majority of
      these loci not just in primates but also across non-primate mammals. Furthermore,
      the patterns of selection in major mammalian clades are not significantly
      different. Using phylogenetically corrected comparative analyses, we find that
      the evolution of two microcephaly loci, ASPM and CDK5RAP2, are correlated with
      neonatal brain size in Glires and Euungulata, the two most densely sampled non
      primate clades. CONCLUSIONS: Together with previous results, this suggests that
      ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size
      in mammals. Nevertheless, several limitations of currently available data and
      gene-phenotype tests are discussed, including sparse sampling across large
      evolutionary distances, averaging gene-wide rates of evolution, potential
      phenotypic variation and evolutionary reversals. We discuss the implications of
      our results for studies of the genetic basis of brain evolution, and explicit
      tests of gene-phenotype hypotheses.

PMID- 24898824
TI  - Carbon nanoparticle-protected aptamers for highly sensitive and selective
      detection of biomolecules based on nuclease-assisted target recycling signal
      amplification.
AB  - Based on the protective properties of carbon nanoparticles for aptamers against
      the digestion of nuclease, we have developed a nuclease-assisted target recycling
      signal amplification method for highly sensitive detection of biomolecules, such
      as ATP and kanamycin. The high binding specificity between aptamers and targets
      leads to excellent selectivity of the assay. 

PMID- 24898823
TI  - Lessons from McCune-Albright syndrome-associated intraductal papillary mucinous
      neoplasms: : GNAS-activating mutations in pancreatic carcinogenesis.
AB  - GNAS-activating mutations are reported in intraductal papillary mucinous
      neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous
      dysplasia, precocious puberty, and cafe au lait spots. Recently, IPMNs have been
      described as a McCune-Albright syndrome-associated tumor, present in about 15% of
      patients. The aim of the present work was to assess the prevalence of polyostotic
      fibrous dysplasia and McCune-Albright syndrome among patients operated on for
      presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1,
      2007, and December 31, 2012, with available imaging were retrospectively screened
      for polyostotic fibrous dysplasia based on their preoperative abdominal or
      thoracoabdominal spiral computed tomography images. Systematic screening of 272
      patients operated on for IPMNs revealed 1 patient with axial and peripheral
      polyostotic fibrous dysplasia and cafe au lait spots on clinical examination
      suggestive of McCune-Albright syndrome. This patient had been operated on for an
      unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an
      intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy
      with gemcitabine for 6 months and was alive without recurrence 6 years later.
      Besides providing additional evidence of a syndromic IPMN as a feature of McCune
      Albright syndrome, this observation is further evidence of the functional
      oncogenic consequences of GNAS mutations in the pancreas. 

PMID- 24898825
TI  - 'They're not witches. ...' Young children and their parents' perceptions and
      experiences of Child and Adolescent Mental Health Services.
AB  - BACKGROUND: Recent initiatives have emphasized the ongoing need to include
      children in healthcare research, which is relevant to the development of both
      paediatric and mental healthcare services. Our aim was to contribute children and
      their parents' perceptions and experiences of Child and Adolescent Mental Health
      Services (CAMHS), with the objective of providing guidance for those wishing to
      improve inclusivity and empowerment. METHOD: We performed a thematic analysis of
      interview data taken from 11 children (9 boys, 2 girls, aged 8-12) and their
      parents (12 mothers, 2 fathers), who had recently been referred to CAMHS for
      mental health and educational problems. RESULTS: Three core themes emerged from
      the data. Fear of the unknown refers to emotional apprehension due to uncertainty
      of what happens in CAMHS. However children also provided useful reassurances for
      future service users. Therapeutic engagement refers to the importance of being
      listened to and building up good relationships with professionals. Finally making
      services acceptable was discussed in terms of issues of accessibility, session
      tolerances and suggestions for the development of child-centred services.
      CONCLUSIONS: Children were able to provide potentially useful opinions of CAMHS.
      In a time of limited resources it is imperative that the voices of children and
      their parents are acknowledged in order to improve accessibility and experiences
      within CAMHS.

PMID- 24898826
TI  - TET2 mutations in cytogenetically normal acute myeloid leukemia: clinical
      implications and evolutionary patterns.
AB  - Mutations of the Ten-Eleven-Translocation 2 (TET2) gene have been identified in
      patients with various myeloid neoplasms, but the clinical relevance of these
      mutations and their timing during disease development in cytogenetically normal
      acute myeloid leukemia (CN-AML) remain unclear. The total coding region of TET2
      was analyzed by direct sequencing in 215 CN-AML patients younger than 60 years
      from multicenter treatment trials AML-SHG 0199 (ClinicalTrials Identifier
      NCT00209833) and 0295. Associations were analyzed in the context of other
      molecular markers, such as CEBPA, DNMT3A, NMP1, FLT3, IDH1/2, RAS, and WT1. To
      investigate the order of appearance of TET2 and concomitant mutations, targeted
      deep resequencing was performed in six patients. At least one sequence variation
      with impact on TET2 protein sequence was found in 13 of the 215 CN-AML patients
      (6%). Patients with TET2 mutations tended to be older (P = 0.078) and had higher
      platelet counts (P = 0.041). TET2-mutated patients were more likely to have
      concomitant NPM1 (11 of 13; P = 0.047) and DNMT3A (10 of 13; P = 0.001) mutations
      but were mutually exclusive to partial tandem duplication of the MLL gene (MLL
      PTD) and IDH1/2 mutations. TET2 mutations were identified as subclones in four of
      the six investigated patients by deep sequencing. Progenitor-derived colony
      assays suggest a stepwise acquisition of mutations during disease development,
      TET2 mutation being later than NPM1 and DNMT3A. The TET2 mutation status did not
      influence overall or relapse-free survival.

PMID- 24898827
TI  - Extramarginal excision is preferable for hypertrophic scars.
AB  - BACKGROUND: Recently, higher proliferative activity and collagen production in
      the peripheral parts of keloids have been reported. Therefore, we hypothesized
      that insufficient removal of active proliferating and collagen-producing
      fibroblasts at the scar margin might cause a high recurrence rate of hypertrophic
      scars and keloids. To address this hypothesis, we evaluated the influence of
      surgical margins on the recurrence of hypertrophic scars and compared the
      recurrence rates between intramarginal excision and extramarginal excision.
      METHODS: A retrospective review was performed of patients with car tire injury
      induced hypertrophic scars treated by surgical excision from 2004 to 2010. To
      evaluate the influence of surgical margins on the recurrence of hypertrophic
      scars, we divided these patients into two groups, the intramarginal excision
      group and the extramarginal excision group, and compared the recurrence rate.
      RESULTS: A total of 15 patients with car tire injury-induced hypertrophic scars
      were treated with surgical excision and skin grafting. The recurrence rate in
      those with intramarginal excision was significantly higher than in those with
      extramarginal excision. All patients treated with intramarginal excision
      experienced hypertrophic scar recurrence within six months. Three of nine
      patients exhibited recurrence when the hypertrophic scars were excised with a 3-5
      mm margin. CONCLUSION: Extramarginal excision with complete removal of the
      abnormal collagen bundles followed by skin grafting is a viable alternative to
      reconstruction of the foot after hypertrophic scar excision, and this treatment
      can effectively decrease issues related to recurrence.

PMID- 24898828
TI  - No association between typical European mitochondrial variation and prostate
      cancer risk in a Spanish cohort.
AB  - Mitochondrial common variants (mtSNPs) and the haplogroups defined by them have
      been inconsistently correlated with increased prostate cancer risk. Here we aimed
      to investigate the influence of the mitochondrial genetic background on prostate
      cancer. A total of 15 single-nucleotide polymorphisms (SNPs) representing the
      common European branches of the mtDNA phylogeny were analyzed in a cohort of 620
      Spanish prostate cancer patients and 616 matched population-based controls.
      Association tests were computed on mtSNPs and haplogroups. None of the evaluated
      mtSNPs or haplogroups were statistically associated with prostate cancer risk in
      our Spanish cohort. We show that previous association findings do not rest on
      solid grounds given that all of them (i) were based on underpowered studies, (ii)
      did not control for population stratification, (iii) lacked
      replication/confirmation cohorts, and (iv) and did not control for multiple test
      corrections. Taken together, a critical reassessment of the previous literature
      and the results obtained in the present study suggest that mtDNA common European
      variants are not correlated with increases in the risk for prostate cancer. 

PMID- 24898830
TI  - Migraine headaches and mood/anxiety disorders in the ELSA Brazil.
AB  - OBJECTIVE: To describe the relationship between mood/anxiety disorders and
      migraine headaches emphasizing the frequency of episodes based in a cross
      sectional analysis in the Brazilian Longitudinal Study of Adult Health.
      BACKGROUND: It has been suggested that frequency of migraine headaches can be
      directly associated with the presence of psychiatric disorders. METHODS: Migraine
      headaches (International Headache Society criteria) was classified as <1*/month,
      1*/month-1*/week, 2-6*/week, and daily. Psychiatric disorders using the Clinical
      Interview Schedule - Revised were classified in 6 categories: common mental
      (CMD), major depressive (MDD), generalized anxiety (GAD), panic, obsessive
      compulsive (OCD), and mixed anxiety and depressive (MADD) disorders. We performed
      multivariate logistic models adjusted for age, race, education, marital status,
      income, and use of selective serotonin reuptake inhibitors. RESULTS: In our
      sample, 1261 presented definite migraine and 10,531 without migraine headaches
      (reference). Our main result was an increase in the strength of association
      between migraine and MDD as frequency of migraine increased for all sample: odds
      ratio of 2.14 (95% confidence interval [CI] 1.33-3.43) for <1 episode of
      migraine/month to 6.94 (95% CI 4.20-11.49) for daily headaches for all sample.
      Significant associations with migraine were also found for GAD, OCD, MADD, and
      CMD for total sample: MDD, GAD, OCD, MADD, and CMD for women, and MADD and CMD
      for men. Among men with daily migraine complaint, we found a significant
      association between migraine and OCD after correction for multiple comparisons
      (odds ratio 29.86 [95% CI 4.66-191.43]). Analyzing probable and definite migraine
      cases together, we replicated the findings in a lower magnitude. CONCLUSIONS: The
      increase in migraine frequency was associated with progressively higher
      frequencies of having mood/anxiety disorders in all samples suggesting for some
      psychiatric disorders a likely dose-response effect especially for women.

PMID- 24898831
TI  - Evaluation of bioaugmentation and biostimulation effects on the treatment of
      refinery oily sludge using 2(n) full factorial design.
AB  - Bioremediation approaches for the treatment of oily sludge from a refinery were
      evaluated using a 2(3) factorial design. The three strategies tested were
      bioaugmentation with indigenous microbial consortia (MO) isolated from oily
      sludge, biostimulation with nutrients (NP) and biostimulation with the surfactant
      Triton X-100 (TX). Eight experimental runs were conducted in triplicate with
      factor settings +/- (high/low) as per the 2(3) design. The main effects and the
      effects of various interactions of the factors on oil degradation and microbial
      growth in suspension were evaluated during a 30 day study. Multifactor ANOVA
      could reveal the significant effects while the normal order score approach failed
      in this scenario. The main effect of biostimulation with nutrients in the form of
      nitrate and phosphate, as well as biostimulation with Triton X-100, was positive
      and significant when both oil degradation and microbial growth in suspension were
      chosen as the response variables. However, the main effect of bioaugmentation was
      only significant for oil degradation but was insignificant for microbial growth
      at a 90% confidence level. The MO-NP binary interaction and the MO-NP-TX ternary
      interactions were positive and significant, indicating the synergistic effect of
      these strategies on oil degradation and microbial growth. All other binary
      interactions were found to be insignificant.

PMID- 24898829
TI  - A case report of two brothers with ATR-X syndrome due to low maternal frequency
      of somatic mosaicism for an intragenic deletion in the ATRX.
AB  - In clinical practice, it is important to diagnose the carrier state of female
      patients with X-linked diseases for genetic counseling to calculate the recurrent
      risk of offspring. Because some X-linked diseases show high rates of gonadal
      mosaicism, this diagnosis is sometimes difficult, when there are few offspring in
      a family and no mutation is detected in the maternal genomic DNA. Here, we report
      two male siblings with ATR-X syndrome carrying an intragenic deletion of 78.6 kb
      involving exons 2-5 out of the 35 exons in the ATRX, as revealed by PCR
      amplification of these exons. The mother was expected to be an obligate carrier,
      but we could not confirm her as a mutation carrier by quantitative PCR (qPCR) for
      the exons. However, we identified the breakpoint of ATRX, and qPCR with
      breakpoint-specific primers revealed gonosomal mosaicism, with a relative
      frequency of the mutation of <1% in genomic DNA of her peripheral blood. For
      these obligate carriers of X-linked disease, we should aggressively investigate
      the maternal genomic status, not only because her genetic condition is important
      for estimating the recurrent risk of her offspring but also because a diagnosis
      of her gonosomal mosaicism can render negligible the possibility that her female
      siblings are carriers. We should reconfirm that a female who has a risk of being
      a carrier has a gonosomal or somatic mutation, even if she is an obligate carrier
      or apparently harbors a mutation. 

PMID- 24898832
TI  - Cognitive impairment in ORIGIN: timing is everything.

PMID- 24898833
TI  - Treatment of hypopituitarism in patients receiving antiepileptic drugs.
AB  - Evidence suggests that there may be drug interactions between antiepileptic drugs
      and hormonal therapies, which can present a challenge to endocrinologists dealing
      with patients who have both hypopituitarism and neurological diseases. Data are
      scarce for this subgroup of patients; however, data for the interaction of
      antiepileptic drugs with the pituitary axis have shown that chronic use of many
      antiepileptic drugs, such as carbamazepine, oxcarbazepine, and topiramate,
      enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum
      concentrations of sex hormones. Other antiepileptic drugs increase sex hormone
      binding globulin, which reduces the bioactivity of testosterone and estradiol.
      Additionally, the combined oestrogen-progestagen contraceptive pill might
      decrease lamotrigine concentrations, which could worsen seizure control.
      Moreover, sex hormones and their metabolites can directly act on neuronal
      excitability, acting as neurosteroids. Because carbamazepine and oxcarbazepine
      can enhance the sensitivity of renal tubules, a reduction in desmopressin dose
      might be necessary in patients with central diabetes insipidus. Although the
      effects of antiepileptic drugs in central hypothyroidism have not yet been
      studied, substantial evidence indicates that several antiepileptic drugs can
      increase thyroid hormone metabolism. However, although it is reasonable to expect
      a need for a thyroxine dose increase with some antiepileptic drugs, the effect of
      excessive thyroxine in lowering seizure threshold should also be considered.
      There are no reports of significant interactions between antiepileptic drugs and
      the efficacy of human growth hormone therapy, and few data are available for the
      effects of second-generation antiepileptic drugs on hypopituitarism treatment. 

PMID- 24898835
TI  - Advanced radioiodine-refractory differentiated thyroid cancer: the sodium iodide
      symporter and other emerging therapeutic targets.
AB  - Approximately 30% of patients with advanced, metastatic differentiated thyroid
      cancer have radioiodine-refractory disease, based on decreased expression of the
      sodium iodide symporter SLC5A5 (NIS), diminished membrane targeting of NIS, or
      both. Patients with radioiodine-refractory disease, therefore, are not amenable
      to (131)I therapy, which is the initial systemic treatment of choice for non
      refractory metastatic thyroid cancer. Patients with radioiodine-refractory cancer
      have historically had poor outcomes, partly because these cancers often respond
      poorly to cytotoxic chemotherapy. In the past decade, however, considerable
      progress has been made in delineating the molecular pathogenesis of radioiodine
      refractory thyroid cancer. As a result of the identification of key genetic and
      epigenetic alterations and dysregulated signalling pathways, multiple
      biologically targeted drugs, in particular tyrosine-kinase inhibitors, have been
      evaluated in clinical trials with promising results and have begun to
      meaningfully impact clinical practice. In this Review, we summarise the current
      knowledge of the molecular pathogenesis of advanced differentiated thyroid cancer
      and discuss findings from clinical trials of targeted drugs in patients with
      radioiodine-refractory disease. Additionally, we focus on the molecular basis of
      loss of NIS expression, function, or both in refractory disease, and discuss
      preclinical and clinical data on restoration of radioiodine uptake. 

PMID- 24898834
TI  - Effects of basal insulin glargine and omega-3 fatty acid on cognitive decline and
      probable cognitive impairment in people with dysglycaemia: a substudy of the
      ORIGIN trial.
AB  - BACKGROUND: Diabetes and non-diabetic dysglycaemia are risk factors for
      accelerated cognitive decline. In this planned substudy of the Outcome Reduction
      with Initial Glargine Intervention (ORIGIN) trial, we assessed whether
      normalising glucose with insulin glargine or administering omega-3 fatty acids in
      this population may slow this process or affect the development of cognitive
      impairment. METHODS: The ORIGIN trial recruited participants older than 50 years
      with dysglycaemia who were taking either no or one oral glucose-lowering drug,
      who had additional risk factors for cardiovascular events, whose HbA1c was less
      than 9%, and who were not taking insulin. Participants were recruited from 573
      sites in 40 countries. Participants were randomly assigned to either titrated
      basal insulin glargine targeting a fasting plasma glucose concentration of 5.3
      mmol/L or lower or standard care and to either omega-3 fatty acid (1 g) or
      placebo by a factorial design. Outcome adjudicators and data analysts were masked
      to treatment allocation. Cognitive function was assessed by the Mini-Mental State
      Examination (MMS) and Digit Symbol Substitution (DSS). The effect of insulin
      glargine or omega-3 fatty * acid on cognitive function over time, the annualised
      change in test scores, and the development of probable cognitive impairment were
      measured. All analyses were restricted to those participants who had a cognitive
      measurement at both baseline and at least one follow-up visit. The ORIGIN trial
      is registered with ClinicalTrials.gov, NCT00069784. FINDINGS: Participants were
      randomly assigned between Sept 1, 2003, and Dec 15, 2005. MMSE and DSS were
      assessed in 11,685 and 3392 ORIGIN participants (mean age 63.4 years [SD 7.7]),
      who were followed up for a median of 6.2 years (IQR 5.8-6.7). There was no
      difference in the rate of change of cognitive test scores between the insulin
      glargine and standard care groups (for the MMSE 0.0046, 95% CI -0.0132 to 0.0224,
      p=0.39; and for the DSS -0.0362, -0.2180 to 0.1455, p=0.34) or between the omega
      3 fatty acid and placebo groups (for the MMSE 0.0013, 95% CI -0.0165 to 0.0191,
      p=0.21; and for the DSS -0.0605, -0.2422 to 0.1212, p=0.72). Similarly, the
      incidence of probable cognitive impairment did not differ between the insulin
      glargine and standard care groups (p=0.065) or the omega-3 fatty acid and placebo
      groups (p=0.070). In a subgroup analysis, allocation to insulin glargine versus
      standard care seemed to reduce the decline in the MMSE (but not the DSS) in
      participants with dysglycaemia but without evidence of diabetes
      (pinteraction=0.024). INTERPRETATION: In this relatively young cohort of people
      with dysglycaemia, insulin mediated normoglycaemia and omega-3 fatty acid for
      over 6 years had a neutral effect on the rate of cognitive decline and on
      incident cognitive impairment. Future studies should assess the effect of these
      interventions in an older cohort or the effect of other glucometabolic
      interventions on cognitive decline. FUNDING: Sanofi.

PMID- 24898837
TI  - Hepatic FGF21 production is increased in late pregnancy in the mouse.
AB  - Female mammals call on hormonally driven metabolic adaptations to meet the energy
      demand of late pregnancy and lactation. These maternal adaptations preserve
      limiting nutrients and promote their transfer to the uterus during pregnancy or
      mammary gland during lactation. The novel metabolic hormone fibroblast growth
      factor-21 (FGF21) was recently shown to increase suddenly at the onset of
      lactation in dairy cows, but whether FGF21 is induced during the reproductive
      cycle of other mammals is unknown. To start addressing this question, we studied
      subsets of mice when virgin (V), on day 18 of pregnancy (P18) and on lactation
      day 1 (L1), L5 and L14. Plasma FGF21 increased from nearly undetectable levels to
      over 8 ng/ml between V and P18 and returned to V levels by L1. Gene expression
      studies showed that liver was the major source of plasma FGF21 at P18 with little
      or no contribution from other known expressing tissues or from the developing
      placenta and mammary epithelial cells. The increased FGF21 production at P18 was
      dissociated from plasma nonesterified fatty acids and liver lipids, unlike that
      seen in fasted V mice. Changes in FGF21 signaling components in target tissues
      were modest except for reduced beta-Klotho and FGFR1c expression in P18 adipose
      tissue. The placenta expressed both beta-Klotho and FGFR1c, raising the
      possibility that it responds to FGF21. In conclusion, maternal FGF21 is increased
      when products of conception account for ~ 40% of maternal weight, suggesting that
      FGF21 orchestrates some of the adaptations needed to meet the energy demand of
      late pregnancy.

PMID- 24898836
TI  - Negative regulation of HIF in skeletal muscle of elite endurance athletes: a
      tentative mechanism promoting oxidative metabolism.
AB  - The transcription factor hypoxia-inducible factor (HIF) has been suggested as a
      candidate for mediating training adaptation in skeletal muscle. However, recent
      evidence rather associates HIF attenuation with a trained phenotype. For example,
      a muscle-specific HIF deletion increases endurance performance, partly through
      decreased levels of pyruvate dehydrogenase kinase 1 (PDK-1). HIF activity is
      regulated on multiple levels: modulation of protein stability, transactivation
      capacity, and target gene availability. Prolyl hydroxylases (PHD1-3) induces HIF
      degradation, whereas factor-inhibiting HIF (FIH) and the histone deacetylase
      sirtuin-6 (SIRT6) repress its transcriptional activity. Together, these negative
      regulators introduce a mechanism for moderating HIF activity in vivo. We
      hypothesized that long-term training induces their expression. Negative
      regulators of HIF were explored by comparing skeletal muscle tissue from
      moderately active individuals (MA) with elite athletes (EA). In elite athletes,
      expression of the negative regulators PHD2 (MA 73.54 +/- 9.54, EA 98.03 +/-
      6.58), FIH (MA 4.31 +/- 0.25, EA 30.96 +/- 7.99) and SIRT6 (MA 0.24 +/- 0.07, EA
      11.42 +/- 2.22) were all significantly higher, whereas the response gene, PDK-1
      was lower (MA 0.12 +/- 0.03, EA 0.04 +/- 0.01). Similar results were observed in
      a separate 6-wk training study. In vitro, activation of HIF in human primary
      muscle cell culture by PHD inactivation strongly induced PDK-1 (0.84 +/- 0.12 vs
      4.70 +/- 0.63), providing evidence of a regulatory link between PHD activity and
      PDK-1 levels in a relevant model system. Citrate synthase activity, closely
      associated with aerobic exercise adaptation, increased upon PDK-1 silencing. We
      suggest that training-induced negative regulation of HIF mediates the attenuation
      of PDK-1 and contributes to skeletal muscle adaptation to exercise. 

PMID- 24898839
TI  - Food intake and energy expenditure are increased in high-fat-sensitive but not in
      high-carbohydrate-sensitive obesity-prone rats.
AB  - Obesity-prone (OP) rodents are used as models of human obesity predisposition.
      The goal of the present study was to identify preexisting defects in energy
      expenditure components in OP rats. Two studies were performed. In the first one,
      male Wistar rats (n = 48) were fed a high-carbohydrate diet (HCD) for 3 wk and
      then a high-fat diet (HFD) for the next 3 wk. This study showed that adiposity
      gain under HCD was 2.9-fold larger in carbohydrate-sensitive (CS) than in
      carbohydrate-resistant (CR) rats, confirming the concept of "carbohydrate
      sensitive" rats. Energy expenditure (EE), respiratory quotient (RQ), caloric
      intake (CI), and locomotor activity measured during HFD identified no differences
      in EE and RQ between fat-resistant (FR) and fat-sensitive (FS) rats, and
      indicated that obesity developed in FS rats only as the result of a larger CI not
      fully compensated by a parallel increase in EE. A specific pattern of spontaneous
      activity, characterized by reduced activity burst intensity, was identified in FS
      rats but not in CS ones. This mirrors a previous observation that under HCD, CS
      but not FS rats, exhibited bursts of activity of reduced intensity. In a second
      study, rats were fed a HFD for 3 wk, and the components of energy expenditure
      were examined by indirect calorimetry in 10 FR and 10 FS rats. This study
      confirmed that a low basal EE, reduced thermic effect of feeding, defective
      postprandial energy partitioning, or a defective substrate utilization by the
      working muscle are not involved in the FS phenotype. 

PMID- 24898838
TI  - A bioinformatic and computational study of myosin phosphatase subunit diversity.
AB  - Variability in myosin phosphatase (MP) subunits may provide specificity in
      signaling pathways that regulate muscle tone. We utilized public databases and
      computational algorithms to investigate the phylogenetic diversity of MP
      regulatory (PPP1R12A-C) and inhibitory (PPP1R14A-D) subunits. The comparison of
      exonic coding sequences and expression data confirmed or refuted the existence of
      isoforms and their tissue-specific expression in different model organisms. The
      comparison of intronic and exonic sequences identified potential expressional
      regulatory elements. As examples, smooth muscle MP regulatory subunit (PPP1R12A)
      is highly conserved through evolution. Its alternative exon E24 is present in
      fish through mammals with two invariant features: 1) a reading frame shift
      generating a premature termination codon and 2) a hexanucleotide sequence
      adjacent to the 3' splice site hypothesized to be a novel suppressor of exon
      splicing. A characteristic of the striated muscle MP regulatory subunit
      (PPP1R12B) locus is numerous and phylogenetically variable transcriptional start
      sites. In fish this locus only codes for the small (M21) subunit, suggesting the
      primordial function of this gene. Inhibitory subunits show little intragenic
      variability; their diversity is thought to have arisen by expansion and tissue
      specific expression of different gene family members. We demonstrate differences
      in the regulatory landscape between smooth muscle enriched (PPP1R14A) and more
      ubiquitously expressed (PPP1R14B) family members and identify deeply conserved
      intronic sequence and predicted transcriptional cis-regulatory elements. This
      bioinformatic and computational study has uncovered a number of attributes of MP
      subunits that supports selection of ideal model organisms and testing of
      hypotheses regarding their physiological significance and regulated expression. 

PMID- 24898841
TI  - Prostaglandin E2 regulation of amnion cell vascular endothelial growth factor
      expression: relationship with intramembranous absorption rate in fetal sheep.
AB  - We hypothesized that prostaglandin E2 (PGE2) stimulates amniotic fluid transport
      across the amnion by upregulating vascular endothelial growth factor (VEGF)
      expression in amnion cells and that amniotic PGE2 concentration correlates
      positively with intramembranous (IM) absorption rate in fetal sheep. The effects
      of PGE2 at a range of concentrations on VEGF 164 and caveolin-1 gene expressions
      were analyzed in cultured ovine amnion cells. IM absorption rate, amniotic fluid
      (AF) volume, and PGE2 concentration in AF were determined in late-gestation fetal
      sheep during control conditions, isovolumic fetal urine replacement (low IM
      absorption rate), or intra-amniotic fluid infusion (high IM absorption rate). In
      ovine amnion cells, PGE2 induced dose- and time-dependent increases in VEGF 164
      mRNA levels and reduced caveolin-1 mRNA and protein levels. VEGF receptor
      blockade abolished the caveolin-1 response, while minimally affecting the VEGF
      response to PGE2. In sheep fetuses, urine replacement reduced amniotic PGE2
      concentration by 58%, decreased IM absorption rate by half, and doubled AF volume
      (P < 0.01). Intra-amniotic fluid infusion increased IM absorption rate and AF
      volume (P < 0.01), while amniotic PGE2 concentration was unchanged. Neither IM
      absorption rate nor AF volume correlated with amniotic PGE2 concentration under
      each experimental condition. Although PGE2 at micromolar concentrations induced
      dose-dependent responses in VEGF and caveolin-1 gene expression in cultured
      amnion cells consistent with a role of PGE2 in activating VEGF to mediate AF
      transport across the amnion, amniotic PGE2 at physiological nanomolar
      concentrations does not appear to regulate IM absorption rate or AF volume.

PMID- 24898840
TI  - The heme oxygenases: important regulators of pregnancy and preeclampsia.
AB  - The heme oxygenase system has long been believed to act largely as a housekeeping
      unit, converting prooxidant free heme from heme protein degradation into the
      benign bilirubin for conjugation and safe excretion. In recent decades, however,
      heme oxygenases have emerged as important regulators of cardiovascular function,
      largely through the production of their biologically active metabolites: carbon
      monoxide, bilirubin, and elemental iron. Even more recently, a number of separate
      lines of evidence have demonstrated an important role for the heme oxygenases in
      the establishment and maintenance of pregnancy. Early preclinical and clinical
      studies have associated defects in the heme oxygenase with the obstetrical
      complication preeclampsia, as well as failure to establish adequate placental
      blood flow, an underlying mechanism of the disorder. Several recent preclinical
      studies have suggested, however, that the heme oxygenase system could serve as a
      valuable therapeutic tool for the management of preeclampsia, which currently has
      few pharmacological options. This review will summarize the role of heme
      oxygenases in pregnancy and highlight their potential in advancing the management
      of patients with preeclampsia. 

PMID- 24898842
TI  - Adrenocortical sensitivity to ACTH in neonatal rats: correlation of
      corticosterone responses and adrenal cAMP content.
AB  - A coordinated hypothalamic-pituitary-adrenal axis response is important for the
      survival of newborns during stress. We have previously shown that prior to
      postnatal day (PD) 5, neonatal rats exposed to hypoxia (one of the most common
      stressors effecting premature neonates) exhibit a large corticosterone response
      with a minimal increase in immunoassayable plasma ACTH and without a detectable
      increase in adrenal cAMP content (the critical second messenger). To explore the
      phenomenon of ACTH-stimulated steroidogenesis in the neonate, we investigated the
      adrenal response to exogenous ACTH in the normoxic neonatal rat. Rat pups at PD2
      and PD8 were injected intraperitoneally with porcine ACTH at low, moderate, or
      high doses (1, 4, or 20 MUg/kg body wt). Trunk blood and whole adrenal glands
      were collected at baseline (before injection) and 15, 30, or 60 min after the
      injection. ACTH stimulated corticosterone release in PD2 and PD8 pups. In PD2
      pups, plasma corticosterone at baseline and during the response to ACTH injection
      was greater than values measured in PD8 pups, despite lower adrenal cAMP content
      in PD2 pups. Specifically, the low and moderate physiological ACTH doses produced
      a large corticosterone response in PD2 pups without a change in adrenal cAMP
      content. At extremely high, pharmacological levels of plasma ACTH in PD2 pups
      (exceeding 3,000 pg/ml), an increase in adrenal cAMP was measured. We conclude
      that physiological increases in plasma ACTH may stimulate adrenal steroidogenesis
      in PD2 pups through a non-cAMP-mediated pathway. 

PMID- 24898843
TI  - Leucine acts in the brain to suppress food intake but does not function as a
      physiological signal of low dietary protein.
AB  - Intracerebroventricular injections of leucine are sufficient to suppress food
      intake, but it remains unclear whether brain leucine signaling represents a
      physiological signal of protein balance. We tested whether variations in dietary
      and circulating levels of leucine, or all three branched-chain amino acids
      (BCAAs), contribute to the detection of reduced dietary protein. Of the essential
      amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10
      MUg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy;
      LP) or normal- (18% protein energy) protein diets induced a divergence in food
      intake, with an increased consumption of LP beginning on day 2 and persisting
      throughout the study (P < 0.05). Circulating BCAA levels were reduced the day
      after LP diet exposure, but levels subsequently increased and normalized by day
      4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis
      on day 2 of diet exposure were reduced in LP rats, but this effect was most
      prominent postprandially. Despite these diet-induced changes in BCAA levels,
      reducing dietary leucine or total BCAAs independently from total protein was
      neither necessary nor sufficient to induce hyperphagia, while chronic infusion of
      EAAs into the brain of LP rats failed to consistently block LP-induced
      hyperphagia. Collectively, these data suggest that circulating BCAAs are
      transiently reduced by dietary protein restriction, but variations in dietary or
      brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet. 

PMID- 24898845
TI  - Quantum resources for purification and cooling: fundamental limits and
      opportunities.
AB  - Preparing a quantum system in a pure state is ultimately limited by the nature of
      the system's evolution in the presence of its environment and by the initial
      state of the environment itself. We show that, when the system and environment
      are initially uncorrelated and arbitrary joint unitary dynamics is allowed, the
      system may be purified up to a certain (possibly arbitrarily small) threshold if
      and only if its environment, either natural or engineered, contains a "virtual
      subsystem" which has the same dimension and is in a state with the desired
      purity. Beside providing a unified understanding of quantum purification dynamics
      in terms of a "generalized swap process," our results shed light on the
      significance of a no-go theorem for exact ground-state cooling, as well as on the
      quantum resources needed for achieving an intended purification task. 

PMID- 24898844
TI  - Roux-en-Y gastric bypass does not affect daily water intake or the drinking
      response to dipsogenic stimuli in rats.
AB  - Bariatric surgery is currently the most effective treatment for severe obesity,
      and Roux-en-Y gastric bypass (RYGB) is the most common approach in the United
      States and worldwide. Many studies have documented the changes in body weight,
      food intake, and glycemic control associated with the procedure. Although
      dehydration is commonly listed as a postoperative complication, little focus has
      been directed to testing the response to dipsogenic treatments after RYGB.
      Accordingly, we used a rat model of RYGB to test for procedure-induced changes in
      daily water intake and in the response to three dipsogenic treatments: central
      administration of ANG II, peripheral injection of hypertonic saline, and
      overnight water deprivation. We did not find any systematic differences in daily
      water intake of sham-operated and RYGB rats, nor did we find any differences in
      the response to the dipsogenic treatments. The results of these experiments
      suggest that RYGB does not impair thirst responses and does not enhance any
      satiating effect of water intake. Furthermore, these data support the current
      view that feedback from the stomach is unnecessary for the termination of
      drinking behavior and are consistent with a role of orosensory or postgastric
      feedback.

PMID- 24898846
TI  - Prognostic value of tumour blood flow, [18F]EF5 and [18F]FDG PET/CT imaging in
      patients with head and neck cancer treated with radiochemotherapy.
AB  - PURPOSE: In order to improve the treatment of squamous cell carcinoma of the head
      and neck, precise information on the treated tumour's biology is required and the
      prognostic importance of different biological parameters needs to be determined.
      The aim of our study was to determine the predictive value of pretreatment PET/CT
      imaging using [(18)F]FDG, a new hypoxia tracer [(18)F]EF5 and the perfusion
      tracer [(15)O]H2O in patients with squamous cell cancer of the head and neck
      treated with radiochemotherapy. METHODS: The study group comprised 22 patients
      with confirmed squamous cell carcinoma of the head and neck who underwent a
      PET/CT scan using the above tracers before any treatment. Patients were later
      treated with a combination of radiochemotherapy and surgery. Parametric blood
      flow was calculated from dynamic [(15)O]H2O PET images using a one-tissue
      compartment model. [(18)F]FDG images were analysed by calculating standardized
      uptake values (SUV) and metabolically active tumour volumes (MATV). [(18)F]EF5
      images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A
      T/M ratio of 1.5 was considered a significant threshold and used to determine
      tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were
      finally correlated with the pretreatment clinical findings (overall stage and TNM
      stage) as well as the outcome following radiochemotherapy in terms of local
      control and overall patient survival. RESULTS: Tumour stage and T-classification
      did not show any significant differences in comparison to the patients' metabolic
      and functional characteristics measured on PET. Using the Cox proportional
      hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR
      = 1.108), maximum [(18)F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p
      = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on
      patient survival in the log-rank test, although [(18)F]EF5 maximum T/M ratio was
      the closest (p = 0.109). By contrast, tumour blood flow was not correlated with
      any of the clinical endpoints. There were no statistically significant
      correlations among [(18)F]FDG SUVmax, [(18)F]EF5 T/M ratio and blood flow.
      CONCLUSION: Our study in a limited number of patients confirmed the importance of
      MATV in the prognosis of locally advanced squamous cell carcinoma of the head and
      neck. It is of interest that high uptake of the hypoxia tracer [(18)F]EF5 showed
      a stronger correlation with a poor clinical outcome than [(18)F]FDG uptake. This
      confirms the importance of hypoxia in treatment outcome and suggests that
      [(18)F]EF5 may act as a surrogate marker of radioresistance.

PMID- 24898847
TI  - MRI and 18F-FDG PET/CT in monitoring the response to neoadjuvant chemotherapy: is
      it necessary to appropriately select the patients?

PMID- 24898849
TI  - Functional Living in Older Adults With Type 2 Diabetes: Executive Functioning,
      Dual Task Performance, and the Impact on Postural Stability and Motor Control.
AB  - OBJECTIVE: Older adults with type 2 diabetes mellitus (DM2) experience
      accelerated age-related decline in some domains of cognition. The present study
      sought to investigate executive functioning and dual tasking capacities in this
      group. METHOD: Older adults with DM2 and age-matched controls completed self
      report measures assessing everyday activities, a comprehensive cognitive battery
      and more specific tasks assessing executive functioning, dual tasking, postural
      stability, and motor control. RESULTS: Executive abilities were particularly
      compromised in the participants with DM2. Furthermore, the DM2 group exhibited
      reduced postural stability under dual task conditions. DISCUSSION: These findings
      suggest that deficits in more complex cognitive activities underlie the decline
      in everyday function in DM2.

PMID- 24898848
TI  - Photoinduced symmetry-breaking intramolecular charge transfer in a quadrupolar
      pyridinium derivative.
AB  - We report here a joint experimental and theoretical study of a quadrupolar, two
      branched pyridinium derivative of interest as a potential non-linear optical
      material. The spectral and photophysical behaviour of this symmetric system is
      greatly affected by the polarity of the medium. A very efficient photoinduced
      intramolecular charge transfer, surprisingly more efficient than in the dipolar
      asymmetric analogue, is found to occur by femtosecond resolved transient
      absorption spectroscopy. TD-DFT calculations are in excellent agreement with
      these experimental findings and predict large charge displacements in the
      molecular orbitals describing the ground state and the lowest excited singlet
      state. The theoretical study also revealed that in highly polar media the
      symmetry of the excited state is broken giving a possible explanation to the
      fluorescence and transient absorption spectra resembling those of the one
      branched analogous compound in the same solvents. The present study may give an
      important insight into the excited state deactivation mechanism of cationic
      (donor-pi-acceptor-pi-donor)(+) quadrupolar compounds characterised by negative
      solvatochromism, which are expected to show significant two-photon absorption
      (TPA). Moreover, the water solubility of the investigated quadrupolar system may
      represent an added value in view of the most promising applications of TPA
      materials in biology and medicine. 

PMID- 24898850
TI  - Formal (4+1) cycloaddition of methylenecyclopropanes with 7-aryl-1,3,5
      cycloheptatrienes by triple gold(I) catalysis.
AB  - 7-Aryl-1,3,5-cycloheptatrienes react intermolecularly with methylenecyclopropanes
      in a triple gold(I)-catalyzed reaction to form cyclopentenes. The same formal
      (4+1) cycloaddition occurs with cyclobutenes. Other precursors of gold(I)
      carbenes can also be used as the C1 component of the cycloaddition. 

PMID- 24898852
TI  - Functional neuroimaging of working memory in survivors of childhood brain tumors
      and healthy children: Associations with coping and psychosocial outcomes.
AB  - PURPOSE: Pediatric brain tumors are the second most common cancer diagnosis in
      individuals under age 20 and research has documented significant neurocognitive,
      psychosocial, and emotional late effects. Associations among these deficits have
      not been adequately considered and the role of survivors' coping with stress in
      relation to deficits is unknown. Further, research has yet to examine
      neurobiological processes related to neurocognitive, psychosocial, and emotional
      difficulties in survivors through the use of functional neuroimaging. METHOD:
      Questionnaire measures and functional neuroimaging were used to examine the
      neurocognitive, psychosocial, and emotional functioning and coping responses of
      survivors of pediatric brain tumors (N = 17; age 8-16) and healthy children (N =
      15). RESULTS: Survivors experienced elevated levels of psychosocial and
      behavioral/emotional difficulties relative to healthy controls and normative
      data. Increases in brain activation in prefrontal and other anterior regions in
      response to a working memory task were associated with better psychosocial
      functioning, use of engagement coping strategies, and less use of disengagement
      coping strategies. Regression analyses suggest coping accounts for a significant
      portion of the association between brain activation and behavioral/emotional
      functioning. CONCLUSIONS: This study extends late-effects research by examining
      neurobiological processes associated with psychosocial and emotional
      difficulties. These findings contribute to our understanding of difficulties in
      survivors and provide a foundation for research exploring these associations and
      mediators of deficits in future longitudinal studies.

PMID- 24898853
TI  - Pyrazolone as a recognition site: Rhodamine 6G-based fluorescent probe for the
      selective recognition of Fe3+ in acetonitrile-aqueous solution.
AB  - Two novel Rhodamine-pyrazolone-based colorimetric off-on fluorescent chemosensors
      for Fe(3+) ions were designed and synthesized using pyrazolone as the recognition
      moiety and Rhodamine 6G as the signalling moiety. The photophysical properties
      and Fe(3+) -binding properties of sensors L(1) and L(2) in acetonitrile-aqueous
      solution were also investigated. Both sensors successfully exhibit a remarkably
      'turn-on' response, toward Fe(3+) , which was attributed to 1: 2 complex
      formation between Fe(3+) and L(1) /L(2) . The fluorescent and colorimetric
      response to Fe(3+) can be detected by the naked eye, which provides a facile
      method for the visual detection of Fe(3+) .

PMID- 24898851
TI  - Internal focus of attention in anxiety-sensitive females up-regulates amygdale
      activity: an fMRI study.
AB  - Cognitive behavioral models of panic disorder (PD) stress the importance of an
      increased attentional focus towards bodily symptoms in the onset and maintenance
      of this debilitating anxiety disorder. In this fMRI mental tracking paradigm, we
      looked at the effects of focusing one's attention internally (interoception) vs.
      externally (exteroception) in a well-studied group at risk for PD-that is anxiety
      sensitive females (AS-high). We hypothesized that AS-high subjects compared to
      control subjects will present higher arousal and decreased valence scores during
      interoception and parallel higher activity in brain areas which are associated
      with fear and interoception. 24 healthy female students with high levels of
      anxiety sensitivity and 24 healthy female students with normal levels of anxiety
      sensitivity serving as control group were investigated by 3 T fMRI. Subjects
      either focused their attention on their heartbeats (internal condition) or on
      neutral tones (external condition). Task performance was monitored by reporting
      the number of heartbeats or tones after each block. State of arousal and
      emotional valence were also assessed. The high anxiety-sensitive group reported
      higher arousal scores compared to controls during the course of the experiment.
      Simultaneously, fMRI results indicated higher activation in anxiety-sensitive
      participants than in controls during interoception in a network of cortical and
      subcortical brain regions (thalamus, amygdala, parahippocampus) that overlaps
      with known fear circuitry structures. In particular, the activity of the right
      amygdala was up-regulated. Future prospective-longitudinal studies are needed to
      validate the role of the amygdala for transition to disorder. Attention to
      internal body functions up-regulates the activity of interoceptive and fear
      relevant brain regions in anxiety-sensitive females, a high-risk group for the
      development of anxiety disorders. 

PMID- 24898854
TI  - Photothermally controlled structural switching in fluorinated polyene-graphene
      hybrids.
AB  - Fluorination of graphene enables tuning of its electronic properties, provided
      that control of the fluorination degree and of modification of graphene structure
      can be achieved. In this work we demonstrate that SF6 modulated plasma
      fluorination of monolayer graphene yields polyene-graphene hybrids. The extent of
      fluorination is determined by the plasma exposure time and controlled in real
      time by monitoring the change in the optical response by spectroscopic
      ellipsometry. Raman spectroscopy reveals the formation of polyenes in partially
      fluorinated graphene (F/C < 0.25), which are responsible for changes in
      conductivity and for opening a transport gap of ~25 meV. We demonstrate that the
      cis- and trans-isomers of the polyenes in graphene are tunable using the
      photothermal switching. Specifically, the room temperature fluorination results
      in the cis-isomer that can be converted to the trans-isomer by annealing at T >
      150  degrees C, whereas photoirradiation activates the trans-to-cis
      isomerization. The two isomers give to the polyene-graphene hybrids different
      optical and conductivity properties providing a way to engineer electrical
      response of graphene. 

PMID- 24898858
TI  - Reduction of condom use errors from a brief, clinic-based intervention: a
      secondary analysis of data from a randomised, controlled trial of young black
      males.
AB  - OBJECTIVE: To test the hypothesis that a brief, clinic-based, single-session
      programme will reduce the rate of 10 selected condom use errors in a clinical
      sample of young black men (YBM) ages 15 through 23 years. METHODS: Data were
      collected in clinics treating patients with sexually transmitted infections (STI)
      in three southern US cities. Males 15-23 years of age who identified as
      black/African-American, and reported recent (past 2 months) condom use were
      eligible. Only those also reporting condom use in the 2 months prior to a 6-month
      follow-up assessment (n=311) were included in this secondary analysis of data
      from a randomised, controlled trial. Difference scores were used to capture a
      Group*Time effect. RESULTS: YBM reported 2232 condom use events in the 2 months
      preceding study enrolment and 2042 in the 2 months preceding the follow-up
      assessment. Mean baseline error rates were 1.32 and 1.13 for young men randomised
      to the intervention and control conditions, respectively. Follow-up rates were
      1.11 and 3.59 for young men randomised to the intervention and control
      conditions, respectively. Controlled findings yielded a significant effect for
      the influence of group assignment on the difference score (baseline to follow-up)
      in the condom use error rate (beta=0.13; p=0.02). CONCLUSIONS: A brief, clinic
      based counselling programme produced modest reductions in condom use errors among
      YBM attending STI clinics in the southern USA Intensified clinic-based
      intervention that helps YBM improve the quality of their condom use behaviours is
      warranted. TRIAL REGISTRATION NUMBER: NCT00849823.

PMID- 24898855
TI  - MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and
      compensates for loss of PINK1/parkin.
AB  - Parkinson's disease (PD) genes PINK1 and parkin act in a common pathway that
      regulates mitochondrial integrity and quality. Identifying new suppressors of the
      pathway is important for finding new therapeutic strategies. In this study, we
      show that MUL1 suppresses PINK1 or parkin mutant phenotypes in Drosophila. The
      suppression is achieved through the ubiquitin-dependent degradation of Mitofusin,
      which itself causes PINK1/parkin mutant-like toxicity when overexpressed. We
      further show that removing MUL1 in PINK1 or parkin loss-of-function mutant
      aggravates phenotypes caused by loss of either gene alone, leading to lethality
      in flies and degeneration in mouse cortical neurons. Together, these observations
      show that MUL1 acts in parallel to the PINK1/parkin pathway on a shared target
      mitofusin to maintain mitochondrial integrity. The MUL1 pathway compensates for
      loss of PINK1/parkin in both Drosophila and mammals and is a promising
      therapeutic target for PD.DOI: http://dx.doi.org/10.7554/eLife.01958.001. 

PMID- 24898861
TI  - Evaluation of active video games intensity: comparison between accelerometer
      based predictions and indirect calorimetric measurements.
AB  - BACKGROUND: Several active video game (AVG) intervention studies failed in
      showing an increase in physical activity by using accelerometry measurements.
      OBJECTIVE: To test the validity of accelerometry for monitoring AVG playing
      intensity. METHOD: Twenty-two adults performed 80 activities included in the Wii
      Sports and Wii Fit Plus series. The energy expenditure (EE) and subsequent MET
      values were measured by indirect calorimetry using metabolic chambers. Subjects
      wore an accelerometer-based monitor displaying MET values. For each activity,
      METs values obtained from indirect calorimetry and accelerometry were compared.
      Each activity was classified as light or moderate to vigorous physical activity
      (LPA: < 3METs or MVPA: ? 3METs) for the two methods. RESULTS: AVG intensities
      have been slightly but significantly underestimated by the acceleromater-based
      monitor compared to the indirect calorimetry (2.5 +/- 1.0 instead of 2.7 +/- 0.9
      METs). Fourty percent of activities have been significantly misestimated, and 20%
      have been misclassified. CONCLUSION: Those results point out the potential bias
      of accelerometry measurements for evaluating AVG intensities. Because average AVG
      intensity lays at the boundary between LPA and MVPA classes, misclassifications
      can frequently occur. Accelerometry data should be interpreted with caution in
      intervention studies using AVG.

PMID- 24898863
TI  - Detection of premature ventricular contractions using the RR-interval signal: a
      simple algorithm for mobile devices.
AB  - BACKGROUND: Premature ventricular contractions (PVCs) are cardiac abnormalities
      that may occur in subjects with/without cardiovascular disorder. Detection is
      usually performed from electrocardiograms (ECGs); heart activity for a long
      period of time must be recorded at hospital or with ambulatory
      electrocardiography. An alternative with a common mobile device would be very
      interesting, because a simple heart rate sensor should be sufficient. OBJECTIVE:
      To develop an algorithm to detect PVCs using the RR-interval (distance between
      consecutive beats) extracted from ECGs or from the heart rate signal captured by
      mobile devices. METHODS: Feature extraction and classification techniques were
      included: 1) two timing interval features (prematurity and compensatory pause)
      were extracted. 2) A linear classifier was applied. To validate the method, the
      MIT-BIH Arrhythmia Database was used. Considering the existence of unbalanced
      classes (normal beats and PVCs) at different decision costs, validation was
      performed with receiver operating characteristic (ROC) analysis. RESULTS: A
      sensitivity of 90.13% and a specificity percentage of 82.52% were achieved. The
      area under the ROC curve (AUC) was 0.928. CONCLUSIONS: The method is advantageous
      since it only uses the RR-interval signal for PVC detection, and results compare
      well with more complex methods that use ECG recording.

PMID- 24898857
TI  - HPTN 035 phase II/IIb randomised safety and effectiveness study of the vaginal
      microbicides BufferGel and 0.5% PRO 2000 for the prevention of sexually
      transmitted infections in women.
AB  - OBJECTIVES: To estimate the effectiveness of candidate microbicides BufferGel and
      0.5% PRO 2000 Gel (P) (PRO 2000) for prevention of non-ulcerative sexually
      transmitted infections (STIs). METHODS: Between 2005 and 2007, 3099 women were
      enrolled in HIV Prevention Trials Network (HPTN) protocol 035, a phase II/IIb
      evaluation of the safety and effectiveness of BufferGel and PRO 2000 for
      prevention of STIs, including Neisseria gonorrhoeae (NG), Chlamydia trachomatis
      (CT) and Trichomonas vaginalis (TV). Incidences of STIs were determined by study
      arm, and HRs of BufferGel and PRO 2000 versus placebo gel or no gel control
      groups were computed using discrete time Andersen-Gill proportional hazards
      model. RESULTS: The overall incidence rates were 1.6/100 person-years at risk
      (PYAR) for NG, 3.9/100 PYAR for CT and 15.3/100 PYAR for TV. For BufferGel versus
      placebo gel, HRs were 0.99 (95% CI 0.49 to 2.00), 1.00 (95% CI 0.64 to 1.57) and
      0.95 (95% CI 0.71 to 1.25) for prevention of NG, CT and TV, respectively. For PRO
      2000, HRs were 1.66 (95% CI 0.90 to 3.06), 1.16 (95% CI 0.76 to 1.79) and 1.18
      (95% CI 0.90 to 1.53) for prevention of NG, CT and TV, respectively. CONCLUSIONS:
      The incidence of STIs was high during HIV Prevention Trials Network 035 despite
      provision of free condoms and comprehensive risk-reduction counselling,
      highlighting the need for effective STI prevention programmes in this population.
      Unfortunately, candidate microbicides BufferGel and PRO2000 had no protective
      effect against gonorrhoea, chlamydia or trichomoniasis. TRIAL REGISTRATION
      NUMBER: NCT00074425.

PMID- 24898862
TI  - Seminal quality prediction using data mining methods.
AB  - BACKGROUND: Now-a-days, some new classes of diseases have come into existences
      which are known as lifestyle diseases. The main reasons behind these diseases are
      changes in the lifestyle of people such as alcohol drinking, smoking, food habits
      etc. After going through the various lifestyle diseases, it has been found that
      the fertility rates (sperm quantity) in men has considerably been decreasing in
      last two decades. Lifestyle factors as well as environmental factors are mainly
      responsible for the change in the semen quality. OBJECTIVE: The objective of this
      paper is to identify the lifestyle and environmental features that affects the
      seminal quality and also fertility rate in man using data mining methods. METHOD:
      The five artificial intelligence techniques such as Multilayer perceptron (MLP),
      Decision Tree (DT), Navie Bayes (Kernel), Support vector machine+Particle swarm
      optimization (SVM+PSO) and Support vector machine (SVM) have been applied on
      fertility dataset to evaluate the seminal quality and also to predict the person
      is either normal or having altered fertility rate. While the eight feature
      selection techniques such as support vector machine (SVM), neural network (NN),
      evolutionary logistic regression (LR), support vector machine plus particle swarm
      optimization (SVM+PSO), principle component analysis (PCA), chi-square test,
      correlation and T-test methods have been used to identify more relevant features
      which affect the seminal quality. These techniques are applied on fertility
      dataset which contains 100 instances with nine attribute with two classes.
      RESULTS: The experimental result shows that SVM+PSO provides higher accuracy and
      area under curve (AUC) rate (94% & 0.932) among multi-layer perceptron (MLP) (92%
      & 0.728), Support Vector Machines (91% & 0.758), Navie Bayes (Kernel) (89% &
      0.850) and Decision Tree (89% & 0.735) for some of the seminal parameters. This
      paper also focuses on the feature selection process i.e. how to select the
      features which are more important for prediction of fertility rate. In this
      paper, eight feature selection methods are applied on fertility dataset to find
      out a set of good features. The investigational results shows that childish
      diseases (0.079) and high fever features (0.057) has less impact on fertility
      rate while age (0.8685), season (0.843), surgical intervention (0.7683), alcohol
      consumption (0.5992), smoking habit (0.575), number of hours spent on setting
      (0.4366) and accident (0.5973) features have more impact. It is also observed
      that feature selection methods increase the accuracy of above mentioned
      techniques (multilayer perceptron 92%, support vector machine 91%, SVM+PSO 94%,
      Navie Bayes (Kernel) 89% and decision tree 89%) as compared to without feature
      selection methods (multilayer perceptron 86%, support vector machine 86%, SVM+PSO
      85%, Navie Bayes (Kernel) 83% and decision tree 84%) which shows the
      applicability of feature selection methods in prediction. CONCLUSION: This paper
      lightens the application of artificial techniques in medical domain. From this
      paper, it can be concluded that data mining methods can be used to predict a
      person with or without disease based on environmental and lifestyle
      parameters/features rather than undergoing various medical test. In this paper,
      five data mining techniques are used to predict the fertility rate and among
      which SVM+PSO provide more accurate results than support vector machine and
      decision tree.

PMID- 24898864
TI  - Outcomes with cementless total hip resurfacing: 5 year follow-up.
AB  - BACKGROUND: Resurfacing Arthroplasty (RA) of the hip has undergone resurgence
      with initially mainly good clinical results in young patients. It was mainly
      performed in younger more active patients with severe symptomatic arthritis of
      the hip including pelvic deformity. Furthermore the proximal femoral anatomy was
      preserved for surgical procedures in the future. OBJECTIVE: The aim of the study
      was to perform a prospective review of the very first 85 hips that had
      implantation of one cementless resurfacing system and a mean follow up of 5
      years. METHODS: 85 cementless Total Hip Resurfacing devices have been performed
      in 75 patients in our orthopaedic department. The mean age of the study group was
      49.8 years. Harries Hip Score, clinical examination data and radiographic
      parameters including the neck shaft angle (NSA), stem shaft angle (SSA) and
      detection of radiolucencies were analyzed. RESULTS: Estimated implant survival at
      five years of follow-up was 88.2% at 5 years follow-up using revision for all
      causes as the end point. Mean HHS was 92.5 (range 80-100) five years after
      Resurfacing Arthroplasty. CONCLUSIONS: In conclusion we have to admit, that there
      was a high proportion of failed hip resurfacings but in the proportion that
      succeeded we saw good clinical results.

PMID- 24898859
TI  - Intramuscular adipogenesis is inhibited by myo-endothelial progenitors with
      functioning Bmpr1a signalling.
AB  - Developing human muscle contains inter-myofibre progenitors expressing Bmp
      receptor 1a (Bmpr1a) and Myf5 that respond to stimulation with Bmp4. Here we
      ablate Bmpr1a in Myf5- and MyoD-expressing cells in vivo. Mutant mice reveal
      increased intramuscular fat and reduced myofibre size in selected muscles, or
      following muscle injury. Myo-endothelial progenitors are the most affected cell
      type: clonal studies demonstrate that ablation of Bmpr1a in myo-endothelial cells
      results in decreased myogenic activity, while adipogenic differentiation is
      significantly increased. Downstream phospho-Smad 1, 5, 8 signalling is also
      severely decreased in mutant myo-endothelial cells. Lineage tracing of
      endothelial cells using VE-cadherin(Cre) driver failed to reveal a significant
      contribution of these cells to developing or injured skeletal muscle. Thus, myo
      endothelial progenitors with functioning Bmpr1a signalling demonstrate myogenic
      potential, but their main function in vivo is to inhibit intramuscular
      adipogenesis, both through a cell-autonomous and a cell-cell interaction
      mechanism. 

PMID- 24898865
TI  - Methodology of developing a smartphone application for crisis research and its
      clinical application.
AB  - BACKGROUND: Recent advancement in Internet based technologies have resulted in
      the growth of a sub-specialized field, termed as "Infodemiology" and
      "Infoveillance". Infoveillence refers to the collation of infodemiology measures
      for the purpose of surveillance and trending. Previous research has only
      demonstrated the research potential of Web 2.0 medium in collation of data in
      crisis situation. OBJECTIVES: The objectives for the current study are to
      demonstrate the methodology of implementation of a smartphone-based application
      for dissemination and collation of information during a crisis situation.
      METHODS: The Haze Smartphone application was developed using an online
      application builder and using HTML5 as the core programming language. A five
      phase developmental method including a) formulation of user requirements, b)
      system design, c) system development, d) system evaluation and finally e) system
      application and implementation were adopted. The smartphone application was
      deployed during a one-week period via a self-sponsored Facebook post and via
      direct dissemination of the web-links by emails. RESULTS: A total of 298
      respondents took part in the survey within the application. Most of them were
      between the ages of 20- to 29-years old and had a university education. More
      individuals preferred the option of accessing and providing feedback to a survey
      on physical and psychological wellbeing via direct access to a Web-based
      questionnaire. In addition, the participants reported a mean number of 4.03
      physical symptoms (SD 2.6). The total Impact of Event Scale-Revised (IES-R) score
      was 18.47 (SD 11.69), which indicated that the study population did experience
      psychological stress but not posttraumatic stress disorder. The perceived
      dangerous Pollutant Standards Index (PSI) level and the number of physical
      symptoms were associated with higher IES-R Score (P<0.05). CONCLUSIONS: This
      study demonstrates how a smartphone application could potentially be used to
      acquire research data in a crisis situation. However, it is crucial for future
      research to further evaluate its effectiveness in a crisis situation.

PMID- 24898866
TI  - Range of motion assessment of the shoulder and elbow joints using a motion
      sensing input device: a pilot study.
AB  - BACKGROUND: Motion sensing input devices could provide a practical and low-cost
      alternative method for repeated range of motion measurements. This study aimed to
      assess the reliability, accuracy and time requirements of a motion sensing input
      device (Microsoft Kinect) for ROM measurements comparing it with goniometer based
      measurements and subjective estimation. MATERIAL AND METHODS: Full ROM was
      measured in 14 shoulder and elbow joints using the different methods. The order
      was randomly selected and each movement was measured twice. The results were
      recorded in degrees and the time measured in seconds. RESULTS: In general, there
      was a poor to moderate agreement between the Kinect system compared to the
      goniometer. There was a good agreement between the goniometer-based and the
      subjective technique. The Kinect-based technique showed excellent test-retest
      reliability. CONCLUSION: The Kinect system showed good test-retest reliability,
      but lower accuracy compared to goniometer-based measurements. Improvements in
      patient positioning and measurement protocol standardization must be made before
      its implementation in clinical practice.

PMID- 24898867
TI  - LWAs computational platform for e-consultation using mobile devices: cases from
      developing nations.
AB  - BACKGROUND: Mobile devices have been impacting on human standard of living by
      providing timely and accurate information anywhere and anytime through wireless
      media in developing nations. Shortage of experts in medical fields is very
      obvious throughout the whole world but more pronounced in developing nations.
      OBJECTIVE: Thus, this study proposes a telemedicine platform for the vulnerable
      areas of developing nations. The vulnerable area are the interior with little or
      no medical facilities, hence the dwellers are very susceptible to sicknesses and
      diseases. METHODS: The framework uses mobile devices that can run LightWeight
      Agents (LWAs) to send consultation requests to a remote medical expert in urban
      city from the vulnerable interiors. The feedback is conveyed to the requester
      through the same medium. The system architecture which contained AgenRoller,
      LWAs, The front-end (mobile devices) and back-end (the medical server) is
      presented. The algorithm for the software component of the architecture
      (AgenRoller) is also presented. The system is modeled as M/M/1/c queuing system,
      and simulated using Simevents from MATLAB Simulink environment. RESULT: The
      simulation result presented show the average queue length, the number of entities
      in the queue and the number of entities departure from the system. These together
      present the rate of information processing in the system. CONCLUSION: A full
      scale development of this system with proper implementation will help extend the
      few medical facilities available in the urban cities in developing nations to the
      interiors thereby reducing the number of casualties in the vulnerable areas of
      the developing world especially in Sub Saharan Africa.

PMID- 24898868
TI  - Design and evaluation of a prototype gait orthosis for early rehabilitation of
      walking.
AB  - BACKGROUND: Rehabilitation of walking should start early after injury to maximise
      the beneficial effects of gait restoration. Most current gait robotic systems are
      not suitable for patients who cannot maintain an upright position. OBJECTIVE:
      This study aimed to develop a prototype to test a supine-stepping system for
      early rehabilitation of walking. METHODS: Based on the pendulum model of walking,
      a supine-stepping system was designed through control of the toe and the ankle
      trajectories. This study implemented the pendulum concept of walking in a
      functional prototype including a bar-cam mechanism and a foot platform that makes
      it possible to perform stepping while lying in a supine position. The kinematics
      of supine stepping produced by the bar-cam prototype were firstly simulated by a
      corresponding bar-cam model in Matlab/Simmechanics, then investigated through a
      preliminary test using an empty leg frame, and lastly by tests on three able
      bodied subjects. The experimental results from the bar-cam prototype were
      compared with the computer simulation results. Furthermore, supine stepping of
      one subject was compared with his performance during overground walking. RESULTS:
      The lower extremity kinematics produced while performing stepping using the
      prototype matched the corresponding simulation results as well as the performance
      during overground walking. CONCLUSIONS: This study demonstrated the technical
      feasibility of implementing the pendulum concept in a gait orthosis for early
      rehabilitation of walking.

PMID- 24898869
TI  - Effect of parent artery expansion by stent placement in cerebral aneurysms.
AB  - BACKGROUND: Stent placement for cerebral aneurysms leads to a decrease in blood
      flow. This occurs not only through the direct obstruction of flow but also by the
      expansion of the parent artery. The latter has been observed in several clinical
      studies. OBJECTIVE: The goal of this study was to clarify the effects of parent
      artery expansion after stent treatment on the following: 1) decrease in blood
      flow to an aneurysm, 2) wall shear stress (WSS), and 3) oscillatory shear index
      (OSI). METHODS: The parent artery geometry constructed U-shape. The aneurysm
      location with respect to the U-shaped parent artery was determined according to
      previous clinical data. We performed calculations in unsteady-state situations
      using constructed models. RESULTS: Parent artery expansion with stent reduces
      blood inflow to an aneurysm and WSS of the aneurysm wall, in addition to
      increasing OSI. The aneurysm position affects the decrease of the inflow rate and
      WSS ratio and increases the OSI ratio. Expansion causes the majority of effects
      on flow reduction inside an aneurysm model. Thus, the expansion effects of all
      samples should not be neglected. CONCLUSION: These data suggest that parent
      artery expansion and its effect should be measured and included in the total
      decrease in blood flow. Parent artery expansion may induce intimal hyperplasia,
      thus increasing the thickness of the aneurysm wall.

PMID- 24898870
TI  - RNA interference technology for anti-VEGF treatment.
AB  - INTRODUCTION: Overexpression of VEGF has been identified to be associated with
      many pathologic processes such as tumors and retinopathy. Inhibiting uncontrolled
      growth of VEGF is a promising strategy to treat these diseases. Currently small
      molecule inhibitors and monoclonal antibodies are the primary treatment. However,
      complex development, short half-life, limited effectiveness and potential
      systemic side effects limited their applications. Highly effective and safe
      therapeutic technologies are highly desirable to meet the growing clinical needs.
      RNA interference (RNAi) technology, inhibits special gene activity at the post
      transcriptional level and reduces the expression of relevant proteins, holding
      great potential due to its easy design and high efficacy. Some molecules based on
      RNAi have been investigating in different clinical trials. AREAS COVERED: In this
      article, we review and consider current advances in the application of RNAi
      technology and potential future clinical strategies. EXPERT OPINION: RNAi
      technology has a promising future in anti-VEGF treatment, most of the
      investigations are encouraging and exciting. More anti-VEGF candidates will enter
      clinical trials and may be a novel therapeutic strategy.

PMID- 24898871
TI  - Single molecule conformational memory extraction: p5ab RNA hairpin.
AB  - Extracting kinetic models from single molecule data is an important route to
      mechanistic insight in biophysics, chemistry, and biology. Data collected from
      force spectroscopy can probe discrete hops of a single molecule between different
      conformational states. Model extraction from such data is a challenging inverse
      problem because single molecule data are noisy and rich in structure. Standard
      modeling methods normally assume (i) a prespecified number of discrete states and
      (ii) that transitions between states are Markovian. The data set is then fit to
      this predetermined model to find a handful of rates describing the transitions
      between states. We show that it is unnecessary to assume either (i) or (ii) and
      focus our analysis on the zipping/unzipping transitions of an RNA hairpin. The
      key is in starting with a very broad class of non-Markov models in order to let
      the data guide us toward the best model from this very broad class. Our method
      suggests that there exists a folding intermediate for the P5ab RNA hairpin whose
      zipping/unzipping is monitored by force spectroscopy experiments. This
      intermediate would not have been resolved if a Markov model had been assumed from
      the onset. We compare the merits of our method with those of others. 

PMID- 24898873
TI  - Gastrointestinal angiodysplasia and bleeding in von Willebrand disease.
AB  - Von Willebrand disease (VWD), the most common genetic bleeding disorder, is
      characterised by a quantitative or qualitative defect of von Willebrand factor
      (VWF). Patients with VWD suffer from mucocutaneous bleeding, of severity usually
      proportional to the degree of VWF defect. In particular, gastrointestinal
      bleeding associated with angiodysplasia is often a severe symptom of difficult
      management. This review focuses on the pathophysiology, diagnosis and treatment
      of VWD-associated gastrointestinal angiodysplasia and related bleeding. 

PMID- 24898872
TI  - Spatial analysis of factors associated with HIV infection among young people in
      Uganda, 2011.
AB  - BACKGROUND: The HIV epidemic in East Africa is of public health importance with
      an increasing number of young people getting infected. This study sought to
      identify spatial clusters and examine the geographical variation of HIV infection
      at a regional level while accounting for risk factors associated with HIV/AIDS
      among young people in Uganda. METHODS: A secondary data analysis was conducted on
      a survey cross-sectional design whose data were obtained from the 2011 Uganda
      Demographic and Health Survey (DHS) and AIDS Indicator Survey (AIS) for 7 518
      young people aged 15-24 years. The analysis was performed in three stages while
      incorporating population survey sampling weights. Maximum likelihood-based
      logistic regression models were used to explore the non-spatially adjusted
      factors associated with HIV infection. Spatial scan statistic was used to
      identify geographical clusters of elevated HIV infections which justified
      modelling using a spatial random effects model by Bayesian-based logistic
      regression models. RESULTS: In this study, 309/533 HIV sero-positive female
      participants were selected with majority residing in the rural areas [386(72%)].
      Compared to singles, those currently [Adjusted Odds Ratio (AOR) =3.64; (95% CI;
      1.25-10.27)] and previously married [AOR = 5.62; (95% CI: 1.52-20.75)]
      participants had significantly higher likelihood of HIV infections. Sexually
      Transmitted Infections [AOR = 2.21; (95% CI: 1.35-3.60)] were more than twice
      likely associated with HIV infection. One significant (p < 0.05) primary cluster
      of HIV prevalence around central Uganda emerged from the SaTScan cluster
      analysis. Spatial analysis disclosed behavioural factors associated with greater
      odds of HIV infection such as; alcohol use before sexual intercourse [Posterior
      Odds Ratio (POR) =1.32; 95% (BCI: 1.11-1.63)]. Condom use [POR = 0.54; (95% BCI:
      0.41-0.69)] and circumcision [POR = 0.66; (95% BCI: 0.45-0.99)] provided a
      protective effect against HIV. CONCLUSIONS: The study revealed associations
      between high-risk sexual behaviour and HIV infection. Behavioural change
      interventions should therefore be pertinent to the prevention of HIV. Spatial
      analysis further revealed a significant HIV cluster towards the Central and
      Eastern areas of Uganda. We propose that interventions targeting young people
      should initially focus on these regions and subsequently spread out across
      Uganda.

PMID- 24898874
TI  - The mixed gold-palladium polyoxo-noble-metalate [NaAu(III)4Pd(II)8O8(AsO4)8](11
      ).
AB  - The first fully inorganic, discrete gold-palladium-oxo complex [NaAu(III) 4
      Pd(II) 8 O8 (AsO4 )8 ](11-) has been synthesized in aqueous medium. The
      combination of single-crystal XRD, elemental analysis, mass spectrometry, and DFT
      calculations allowed establishing the structure and composition of the novel
      polyanion, and UV/Vis studies suggest that it is stable in neutral aqueous media.

PMID- 24898875
TI  - Electrospun meshes possessing region-wise differences in fiber orientation,
      diameter, chemistry and mechanical properties for engineering bone-ligament-bone
      tissues.
AB  - Although bone-patellar tendon-bone (B-PT-B) autografts are the gold standard for
      repair of anterior cruciate ligament ruptures, they suffer from drawbacks such as
      donor site morbidity and limited supply. Engineered tissues modeled after B-PT-B
      autografts are promising alternatives because they have the potential to
      regenerate connective tissue and facilitate osseointegration. Towards the long
      term goal of regenerating ligaments and their bony insertions, the objective of
      this study was to construct 2D meshes and 3D cylindrical composite scaffolds -
      possessing simultaneous region-wise differences in fiber orientation, diameter,
      chemistry and mechanical properties - by electrospinning two different polymers
      from off-set spinnerets. Using a dual drum collector, 2D meshes consisting of an
      aligned polycaprolactone (PCL) fiber region, randomly oriented poly(lactide-co
      glycolide) (PLGA) fiber region and a transition region (comprised of both PCL and
      PLGA fibers) were prepared, and region-wise differences were confirmed by
      microscopy and tensile testing. Bone marrow stromal cells (BMSCs) cultured on
      these meshes exhibited random orientations and low aspect ratios on the random
      PLGA regions, and high aspect ratios and alignment on the aligned PCL regions.
      Next, meshes containing an aligned PCL region flanked by two transition regions
      and two randomly oriented PLGA regions were prepared and processed into 3D
      cylindrical composite scaffolds using an interpenetrating photo-crosslinkable
      polyethylene glycol diacrylate hydrogel to recapitulate the shape of B-PT-B
      autografts. Tensile testing indicated that cylindrical composites were
      mechanically robust, and eventually failed due to stress concentration in the
      aligned PCL region. In summary, this study demonstrates a process to fabricate
      electrospun meshes possessing region-wise differences in properties that can
      elicit region-dependent cell responses, and be readily processed into scaffolds
      with the shape of B-PT-B autografts.

PMID- 24898876
TI  - Are anthropomorphic persuasive appeals effective? The role of the recipient's
      motivations.
AB  - Anthropomorphic persuasive appeals are prevalent. However, their effectiveness
      has not been well studied. The present research addresses this issue with two
      experiments in the context of environmental persuasion. It shows that
      anthropomorphic messages, relative to non-anthropomorphic ones, appear to
      motivate more conservation behaviour and elicit more favourable message responses
      only among recipients who have a strong need for effectance or social connection.
      Among recipients whose such need is weak, anthropomorphic appeals seem to
      backfire. These findings extend the research on motivation and persuasion and add
      evidence to the motivational bases of anthropomorphism. In addition, joining some
      recent studies, the present research highlights the implications of
      anthropomorphism of nature for environmental conservation efforts, and offers
      some practical suggestions for environmental persuasion. 

PMID- 24898877
TI  - High-yield fabrication of nm-size gaps in monolayer CVD graphene.
AB  - Herein we demonstrate the controlled and reproducible fabrication of sub-5 nm
      wide gaps in single-layer graphene electrodes. The process is implemented for
      graphene grown via chemical vapor deposition using an electroburning process at
      room temperature and in vacuum. A yield of over 95% for the gap formation is
      obtained. This approach allows producing single-layer graphene electrodes for
      molecular electronics at a large scale. Additionally, from Raman spectroscopy and
      electroburning carried out simultaneously, we can follow the heating process and
      infer the temperature at which the gap formation happens. 

PMID- 24898879
TI  - An asymptomatic papulopustular eruption in an immunosuppressed patient.

PMID- 24898878
TI  - MiR-23a-mediated migration/invasion is rescued by its target, IRS-1, in non-small
      cell lung cancer cells.
AB  - PURPOSE: To determine the interaction between insulin receptor substrate-1 (IRS
      1) and miR-23a on the migration and invasion of non-small cell lung cancer
      (NSCLC) cells, and to examine IRS-1 expression in NSCLC tissues and its
      correlation with clinicopathologic characteristics. METHODS: The migration and
      invasion of A549 cells were measured using transwell assay. miR-23a levels were
      examined by quantitative reverse transcription-PCR and IRS-1 expression by
      Western blotting. The interaction between miR-23a and IRS-1 was examined by
      luciferase reporter assay. IRS-1 expression in 105 NSCLC specimens was determined
      by immunohistochemistry and its correlation with patient clinicopathologic
      characteristics was evaluated. RESULTS: Transwell assay revealed that miR-23a
      significantly promoted the migration and invasion of A549 cells with a 44.0 and
      44.6 % increase in the number of migrated and invading cells, respectively.
      Luciferase assay showed that miR-23a markedly reduced luciferase activities of
      A549 cells co-transfected with plasmids overexpressing the 3' UTR of IRS-1 mRNA
      (P < 0.05). Co-transfection of A549 cells with miR-23a and plasmids
      overexpressing IRS-1 significantly reduced the increase in the number of migrated
      and invading cells mediated by miR-23a. Immunohistochemistry showed low IRS-1
      expression in 26.7 % and high IRS-1 expression in 73.3 % of the NSCLC specimens.
      Kaplan-Meier analysis revealed that the overall survival and disease-free
      survival of NSCLC were markedly longer in patients with high IRS-1 expression
      than those with low IRS-1 expression (P = 0.002). Multivariate Cox regression
      analysis showed that IRS-1 was an independent prognostic factor for the overall
      survival of NSCLC patients (RR 0.413 CI 0.238-0.718, P = 0.002). CONCLUSIONS:
      There is an interaction between miR-23a and IRS-1 in the modulation of the
      migration and invasion of NSCLC cells. IRS-1 is variably expressed in NSCLC
      patients and correlates with NSCLC patient survival.

PMID- 24898880
TI  - Methylenetetrahydrofolate reductase gene C677T, A1298C polymorphisms and pre
      eclampsia risk: a meta-analysis.
AB  - To determine whether methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C
      polymorphisms are associated with pre-eclampsia susceptibility. Literature
      searches of the Pubmed, Embase, BIOSIS Previews and Web of Science were conducted
      to identify all eligible articles up to January 18th, 2013. The pooled odds
      ratios (ORs) with 95% confidence intervals (CIs) of five genetic models were
      calculated by fixed-effects or random-effects model. Publication bias, subgroup
      analysis, meta-regression and sensitivity analysis were also performed. A number
      of 49 studies including 51 samples consisted of 18,009 subjects (6,238 patients
      and 11,771 controls) were finally included. MTHFR C677T allele (TT or CT)
      carriers were 1.12 times more likely to develop pre-eclampsia (95% CI 1.04-1.21)
      compared with 677CC homozygous individuals. Similar results were obtained under
      other genetic models. Restricted to severe pre-eclampsia, there was an increased
      risk for 677TT homozygotes compared with 677CC homozygotes (OR 1.43; 95% CI 1.12
      1.83). Subgroup analysis revealed a significant positive association between the
      C677T polymorphism (TT or CT) and pre-eclampsia in Asians (OR 1.41; 95% CI 1.11
      1.79) and white population (OR 1.14; 95% CI 1.03-1.25). Meta-regression showed
      that study population, blinded genotyping, matching of cases and controls were
      not substantial sources of heterogeneity. For the MTHFR A1298C, ORs for all
      genetic models yielded a null association. This meta-analysis suggests that the
      MTHFR 677T allele might be associated with increased pre-eclampsia risk in Asian
      and white ethnicity and the subgroup of severe pre-eclampsia, while no
      association is observed between the MTHFR A1298C polymorphism and pre-eclampsia.

PMID- 24898881
TI  - Fatty acid profiles and antioxidants of organic and conventional milk from low-
      and high-input systems during outdoor period.
AB  - BACKGROUND: Intensification of organic dairy production leads to the question of
      whether the implementation of intensive feeding incorporating maize silage and
      concentrates is altering milk quality. Therefore the fatty acid (FA) and
      antioxidant (AO) profiles of milk on 24 farms divided into four system groups in
      three replications (n = 71) during the outdoor period were analyzed. In this
      system comparison, a differentiation of the system groups and the effects of the
      main system factors 'intensification level' (high-input versus low-input) and
      'origin' (organic versus conventional) were evaluated in a multivariate
      statistical approach. RESULTS: Consistent differentiation of milk from the system
      groups due to feeding-related impacts was possible in general and on the basis of
      15 markers. The prediction of the main system factors was based on four or five
      markers. The prediction of 'intensification level' was based mainly on CLA c9,t11
      and C18:1 t11, whereas that of 'origin' was based on n-3 PUFA. CONCLUSION: It was
      possible to demonstrate consistent differences in the FA and AO profiles of
      organic and standard conventional milk samples. Highest concentrations of
      nutritionally beneficial compounds were found in the low-input organic system.
      Adapted grass-based feeding strategies including pasture offer the potential to
      produce a distinguishable organic milk product quality.

PMID- 24898883
TI  - Cytogenetic biomonitoring in oral leukoplakia patients with mild dysplasia.
AB  - OBJECTIVE: A study is made of DNA damage and apoptosis in a group of patients
      with oral leukoplakia (OL) with mild dysplasia. MATERIALS AND METHODS: The study
      comprised 30 patients with a clinicopathological diagnosis of OL with mild
      dysplasia and 30 controls. Both samples were similar in terms of age and gender
      distribution. Brush samples of lesion epithelial cells were collected, followed
      by cell centrifugation, preparation of the slides, fixation and staining, and
      analysis under the fluorescent light microscope. The exfoliated cells were
      examined to detect micronuclei (MN), nuclear buds, binucleated cells, condensed
      chromatin, pyknosis, and cells with karyorrhexis and karyolysis. RESULTS: The
      patients with OL with mild dysplasia showed a greater frequency of MN (P <
      0.001), nuclear buds (P = 0.018), and binucleated cells (P = 0.008). CONCLUSIONS:
      Cytogenetic biomonitoring is a simple and scantly invasive technique allowing
      clinicians to assess DNA damage and apoptosis in patients with OL. CLINICAL
      RELEVANCE: Oral cancer should be detected and controlled in its precancerous
      stages in order to increase survival rates. Leukoplakia lesions must be
      biomonitorized periodically. Biomonitorization offers sensibility, no morbidity,
      speed, and low cost.

PMID- 24898882
TI  - Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates
      with human oesophageal squamous cell carcinoma.
AB  - The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear
      translocation of proteins and certain RNAs from the nucleus to the cytoplasm and
      is thus crucial for the correct localisation of cellular components. Crm1 has
      recently been reported to be highly expressed in certain types of cancers, yet
      its expression in oesophageal cancer has not been investigated to date. We
      investigated the expression of Crm1 in normal and tumour tissues derived from 56
      patients with human oesophageal squamous cell carcinoma and its functional
      significance in oesophageal cancer cell line models. Immunohistochemistry
      revealed that Crm1 expression was significantly elevated in oesophageal tumour
      tissues compared to normal tissues and its localisation shifted from
      predominantly nuclear to nuclear and cytoplasmic. Real-time RT-PCR revealed that
      Crm1 expression was elevated at the mRNA level. To determine the functional
      significance of elevated Crm1 expression in oesophageal cancer, its expression
      was inhibited using siRNA, and a significant decrease in cell proliferation was
      observed associated with G1 cell cycle arrest and the induction of apoptosis.
      Similarly, leptomycin B (LMB) treatment resulted in the effective killing of
      oesophageal cancer cells at nanomolar concentrations. Normal oesophageal
      epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA
      and LMB. Together, this study reveals that Crm1 expression is increased in
      oesophageal cancer and is required for the proliferation and survival of
      oesophageal cancer cells.

PMID- 24898884
TI  - Cardiac tamponade and para-aortic hematoma post elective surgical myocardial
      revascularization on a beating heart - a possible complication of the Lima-stitch
      and sequential venous anastomosis.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery can be associated
      with some intrinsic, but relatively rare complications. A pericardial effusion is
      a common finding after cardiac surgeries, but the prevalence of a cardiac
      tamponade does not exceed 2% and is less frequent after myocardial
      revascularization.Authors believe that in our patient an injury of a nutritional
      pericardial or descending aorta vessel caused by the Lima stitch resulted in
      oozing bleeding, which gradually leaded to cardiac tamponade. The bleeding
      increased after introduction of double antiplatelet therapy and caused life
      threatening hemodynamic destabilization. According to our knowledge it is the
      first report of such a complication after OPCAB. CASE PRESENTATION: We present a
      case of a 61-year old man, who underwent elective surgical myocardial
      revascularization on a beating heart. On the 11th postoperative day the patient
      was readmitted emergently to the intensive care unit for severe chest pain,
      dyspnoea and hypotension. Coronary angiographic control showed a patency of the
      bypass grafts and significant narrowing of circumflex artery, treated with
      angioplasty and stenting. The symptoms and hemodynamic instability exacerbated. A
      suspicion of dissection of the ascending aorta and para-aortic hematoma was
      stated on 16-slice cardiac computed tomography. The patient was referred to the
      Cardiovascular Surgery Clinic. Transthoracic echocardiography revealed cardiac
      tamponade. On transesophageal echocardiography there were no signs of the
      ascending aorta dissection, but a possible lesion of the descending aorta with
      para-aortic hematoma was visualized. Emergent rethoracotomy and cardiac tamponade
      decompression were performed. 12 days after intervention the control 64-slice
      computed tomography showed no lesions of the ascending or descending aorta. On
      one-year follow-up patient is in a good condition, the left ventricular function
      is preserved and there is no pathology in thoracic aorta on echocardiography.
      CONCLUSIONS: Mechanical complications of surgical myocardial revascularization on
      a beating heart should be considered as a cause of the clinical and hemodynamic
      instability relatively early in the postoperative period. Echocardiographic
      examination must be the first step in diagnostics process in a patient after
      cardiac surgery.

PMID- 24898885
TI  - A novel treatment option for MRSA pneumonia: ceftaroline fosamil-yielding new
      hope in the fight against a persistent infection.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired pneumonia
      (HAP) and healthcare-associated pneumonia (HCAP) patients treated with current
      antibiotic therapies have exhibited poor outcomes, increased hospital length of
      stay, and higher costs of care. The optimal management of these infections is
      undetermined; thus, it is critical to look at ways to improve outcomes in these
      patients. There is insufficient data on clinical efficacy in patients with MRSA
      HAP or HCAP infection treated with ceftaroline-fosamil. In a recent pilot study,
      nearly 90% of patients treated with ceftaroline-fosamil survived, despite the
      difficulties associated with administrating bactericidal antimicrobial therapy
      for this increasingly resistant pathogen. These data suggest a possible benefit
      in the use of ceftaroline-fosamil for MRSA pneumonia. Presently, we have
      identified cases over a two-year period treated with ceftaroline-fosamil, and
      will conduct a comparative analysis to controls (those treated with vancomycin
      and/or cefepime, and linezolid) to determine optimal therapeutic agents; these
      findings will have important implications for control of further spread of
      infection, recurrence, readmission, and mortality attributable to MRSA HAP and
      HCAP. 

PMID- 24898886
TI  - Comparison of multiple DNA vaccines for protection against cytomegalovirus
      infection in BALB/c mice.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) causes serious HCMV-related diseases in
      immunocompromised people. Vaccination is the most effective measure to control
      infection with the pathogen, yet no vaccine has been licensed till now. We
      performed a head-to-head comparison of the protective abilities of multiple DNA
      vaccines in murine model of murine cytomegalovirus (MCMV) infection. METHODS:
      Five DNA vaccines were constructed. Four encoding MCMV proteins gp34 (m04), p65
      (M84), DNA helicase (M105), and immediate-early 1 protein pp89 (IE-1) ,
      respectively, which were reported to induce CD8+ T cell responses, were compared
      with the one expressing gB (M55), the neutralizing antibody target antigen, for
      immune protection in BALB/c mice. Mice were immunized with these DNA vaccines 1
      to 4 times via intramuscular injection followed by electroporation, and were
      subsequently infected with a lethal dose (3 * LD50) of highly virulent SG-MCMV.
      Specific antibodies and IFN-gamma secreting splenocytes were detected by
      immunoblotting and ELISPOT, respectively. Protective abilities in mice provided
      by the vaccines were evaluated by residual virus titers in organs, survival rate
      and weight loss. RESULTS: These DNA vaccines, especially m04, M84 and IE-1, could
      effectively reduce the virus loads in salivary glands and spleens of mice, but
      they couldn't completely clear the residual virus. Survival rates of 100% in mice
      after a lethal dose of MCMV infection could be reached by more than one dose of
      M84 vaccine or two doses of m04 or IE-1 vaccine. Immunization with M55 or M105
      DNA at four doses offered mice only 62.5% survival rate after the lethal
      challenge. CONCLUSIONS: The study demonstrated that DNA vaccines could
      effectively afford mice protection against infection with a highly virulent MCMV
      and that the protection offered by induced CD8+ T cell immunity might be superior
      to that by gB-specific antibodies. These results are valuable references for
      development and application of HCMV vaccines.

PMID- 24898888
TI  - Procalcitonin fails to predict bacteremia in SIRS patients: a cohort study.
AB  - BACKGROUND: Procalcitonin (PCT) has previously been proposed as useful marker to
      rule out bloodstream-infection (BSI). The objective of this study was to evaluate
      the sensitivity of different PCT cut-offs for prediction of BSI in patients with
      community (CA)- and hospital-acquired (HA)-BSI. METHODS: A total of 898 patients
      fulfilling systemic-inflammatory-response-syndrome (SIRS) criteria were enrolled
      in this prospective cohort study at the Medical University of Graz, Austria. Of
      those 666 patients had positive blood cultures (282 CA-BSI, 384 HA-BSI, enrolled
      between January 2011 and December 2012) and 232 negative blood cultures (enrolled
      between January 2011 and July 2011 at the emergency department). Blood samples
      for determination of laboratory infection markers (e.g. PCT) were collected
      simultaneously with blood cultures. RESULTS: Procalcitonin was significantly (p <
      0.001) higher in SIRS patients with bacteremia/fungemia than in those without.
      Receiver operating characteristic curve analysis revealed an area under the curve
      (AUC) value of 0.675 for PCT (95% CI 0.636-0.714) for differentiating patients
      with BSI from those without. AUC for IL-6 was 0.558 (95% CI 0.515-0.600).
      However, even at the lowest cut-off evaluated (i.e. 0.1 ng/ml) PCT failed to
      predict BSI in 7% (n = 46) of patients. In the group of patients with SIRS and
      negative blood culture 79% (n = 185) had PCT levels > 0.1. CONCLUSION:
      Procalcitonin was significantly higher in patients with BSI than in those without
      and superior to IL-6 and CRP. The clinical importance of this is questionable,
      because a suitable PCT threshold for excluding BSI was not established. An
      approach where blood cultures are guided by PCT only can therefore not be
      recommended.

PMID- 24898889
TI  - Characterization of a novel HLA-A*33 allele, A*33:47, using next-generation
      sequencing.
AB  - HLA-A*33:47 has a single nucleotide difference to A*33:03:01 at position 181, G >
      C, in exon 2.

PMID- 24898887
TI  - Interleukin-37 mediates the antitumor activity in hepatocellular carcinoma: role
      for CD57+ NK cells.
AB  - The biological role of interleukin-37 (IL-37) in cancer is large unknown. Through
      immunohistochemical detection using 163 primary hepatocellular carcinoma (HCC)
      clinical specimens, we found the expression of IL-37 was decreased in tumor
      tissues, and the expression level was negatively correlated with tumor size. High
      expression of IL-37 in HCC tumor tissues was associated with better overall
      survival (OS) and disease-free survival (DFS). IL-37 expression in tumor tissues
      was positively associated with the density of tumor-infiltrating CD57+ natural
      killer (NK) cells, but not with the CD3+ and CD8+ T cells. Consistently, in vitro
      chemotaxis analysis showed that IL-37- overexpressing HCC cells could recruit
      more NK cells. The in vivo mouse model experiments also revealed that
      overexpression IL-37 in HCC cells significantly delayed tumor growth and
      recruited more NK cells into tumors tissues. Our finding suggested that IL-37
      might play an important role for the prognosis of HCC patients via regulating
      innate immune-action. 

PMID- 24898890
TI  - Liver metastases from esophageal carcinoma: is there a role for surgical
      resection?
AB  - Esophageal cancer recurrence rates after esophagectomy are high, and locally
      recurrent or distant metastatic disease has poor prognosis. Management is limited
      to palliative chemotherapy and symptomatic interventions. We report our
      experience of four patients who have undergone successful liver resection for
      metastases from esophageal cancer. All underwent esophagectomy and were referred
      to our unit with metastatic recurrent liver disease, two with solitary metastases
      and two with multi-focal disease. The patients underwent multidisciplinary
      assessment and proceeded to a course of neoadjuvant chemotherapy followed by open
      or laparoscopic liver resection. Three patients were male, and the mean age was
      57.5 (range 44-71) years. Response to chemotherapy ranged from partial to
      complete response. Following liver resection, two patients developed recurrent
      disease at 5 and 15 months, and both had disease-specific mortality at 10 and 21
      months, respectively. The other two patients remain disease free at 22 and 92
      months. Recurrent metastatic esophageal cancer continues to have a poor
      prognosis, and the majority of patients with liver involvement will not be
      candidates for hepatic resection. However, this series suggests that in selected
      patients, liver resection of metastases from esophageal cancer combined with
      neoadjuvant and adjuvant chemotherapy is feasible, but further research is
      required to determine whether this can offer a survival advantage. 

PMID- 24898891
TI  - Effect of malarial infection on haematological parameters in population near
      Thailand-Myanmar border.
AB  - BACKGROUND: Malaria is a major mosquito-borne public health problem in Thailand
      with varied haematological consequences. The study sought to elucidate the
      haematological changes in people who suspected malaria infection and their
      possible predictive values of malaria infection. METHODS: Haematological
      parameters of 4,985 patients, including 703 malaria-infected and 4,282 non
      malaria infected, who admitted at Phop Phra Hospital, Tak Province, an area of
      malaria endemic transmission in Thailand during 2009 were evaluated. RESULTS: The
      following parameters were significantly lower in malaria-infected patients; red
      blood cells (RBCs) count, haemoglobin (Hb), platelets count, white blood cells
      (WBCs) count, neutrophil, monocyte, lymphocyte and eosinophil counts, while mean
      corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), Mean corpuscular
      haemoglobin concentration (MCHC), neutrophil-lymphocyte ratio (NLR), and monocyte
      lymphocyte ratio (MLR) were higher in comparison to non-malaria infected
      patients. Patients with platelet counts < 150,000/uL were 31.8 times (odds ratio)
      more likely to have a malaria infection. Thrombocytopenia was present in 84.9% of
      malaria-infected patients and was independent of age, gender and nationality (P
      value < 0.0001). CONCLUSION: Patients infected with malaria exhibited important
      changes in most of haematological parameters with low platelet, WBCs, and
      lymphocyte counts being the most important predictors of malaria infection. When
      used in combination with other clinical and microscopy methods, these parameters
      could improve malaria diagnosis and treatment.

PMID- 24898892
TI  - MDM2-MOF-H4K16ac axis contributes to tumorigenesis induced by Notch.
AB  - Identification of the epigenetic mechanisms involved in the transmission of Notch
      signaling is useful for personalized medicine. We observed that aberrantly high
      levels of Notch activity resulted in H4K16ac downregulation in hepatocellular
      carcinoma and breast cancer cell lines and tissues. This downregulated
      acetylation was a consequence of increased male on the first degradation
      following the upregulation of full-length murine double minute 2 in different
      cancer types. We observed that increases in male on the first could attenuate
      heterogeneity induced by aberrantly high levels of Notch activity. Our results
      provide new insights into the analysis and treatment of Notch-induced
      hepatocellular carcinoma and breast cancer. 

PMID- 24898894
TI  - From three sides now: reflections on an ICU journey as patient, parent, and
      researcher.

PMID- 24898893
TI  - Half of the family members of critically ill patients experience excessive
      daytime sleepiness.
AB  - BACKGROUND: Sleepiness and fatigue are commonly reported by family members of
      intensive care unit (ICU) patients. Sleep deprivation may result in cognitive
      deficits. Sleep deprivation and cognitive blunting have not been quantitatively
      assessed in this population. We sought to determine the proportion of family
      members of ICU patients that experience excessive daytime sleepiness, sleep
      associated functional impairment, and cognitive blunting. METHODS: Multicenter,
      cross-sectional survey of family members of patients admitted to ICUs at the
      University of Maryland Medical Center, Johns Hopkins University Hospital, and
      Christiana Hospital. Family members of ICU patients were evaluated using the
      Epworth Sleepiness Scale, a validated survey assessing sleepiness in everyday
      situations (normal, less than 10); the Functional Outcomes of Sleep Questionnaire
      10 (FOSQ-10), a questionnaire quantifying the impact of sleepiness on daily
      activities (normal, at least 17.9); and psychomotor vigilance testing, a test of
      cognitive function, in relation to sleep deprivation (normal mean reaction time
      less than 500 ms). RESULTS: A total of 225 family members were assessed. Of
      these, 50.2 % (113/225) had Epworth scores consistent with excessive daytime
      sleepiness. Those with sleepiness experienced greater impairment in performing
      daily activities by FOSQ-10 (15.6 +/- 3.0 vs 17.4 +/- 2.2, p < 0.001). Cognitive
      blunting was found in 13.3 % (30/225) of family members and 15.1 % (14/93) of
      surrogate decision-makers. Similar rates of cognitive blunting as reported by
      mean reaction time of at least 500 ms were found among family members whether or
      not they reported sleepiness (15.0 % (17/113) vs. 11.6 % (13/112), p = 0.45).
      CONCLUSIONS: Half of the family members of ICU patients suffer from excessive
      daytime sleepiness. This sleepiness is associated with functional impairment, but
      not cognitive blunting.

PMID- 24898895
TI  - Acute respiratory distress syndrome in patients with malignancies.
AB  - PURPOSE: Little attention has been given to ARDS in cancer patients, despite
      their high risk for pulmonary complications. We sought to describe outcomes in
      cancer patients with ARDS meeting the Berlin definition. METHODS: Data from a
      cohort of patients admitted to 14 ICUs between 1990 and 2011 were used for a
      multivariable analysis of risk factors for hospital mortality. RESULTS: Of 1,004
      included patients (86 % with hematological malignancies and 14 % with solid
      tumors), 444 (44.2 %) had neutropenia. Admission SOFA score was 12 (10-13).
      Etiological categories were primary infection-related ARDS (n = 662, 65.9 %; 385
      bacterial infections, 213 invasive aspergillosis, 64 Pneumocystis pneumonia);
      extrapulmonary septic shock-related ARDS (n = 225, 22.4 %; 33 % candidemia);
      noninfectious ARDS (n = 76, 7.6 %); and undetermined cause (n = 41, 4.1 %). Of
      387 (38.6 %) patients given noninvasive ventilation (NIV), 276 (71 %)
      subsequently required endotracheal ventilation. Hospital mortality was 64 %
      overall. According to the Berlin definition, 252 (25.1 %) patients had mild, 426
      (42.4 %) moderate and 326 (32.5 %) severe ARDS; mortality was 59, 63 and 68.5 %,
      respectively (p = 0.06). Mortality dropped from 89 % in 1990-1995 to 52 % in 2006
      2011 (p < 0.0001). Solid tumors, primary ARDS, and later admission period were
      associated with lower mortality. Risk factors for higher mortality were
      allogeneic bone-marrow transplantation, modified SOFA, NIV failure, severe ARDS,
      and invasive fungal infection. CONCLUSIONS: In cancer patients, 90 % of ARDS
      cases are infection-related, including one-third due to invasive fungal
      infections. Mortality has decreased over time. NIV failure is associated with
      increased mortality. The high mortality associated with invasive fungal
      infections warrants specific studies of early treatment strategies.

PMID- 24898896
TI  - Innovations that could improve early recognition of ventilator-associated
      pneumonia.

PMID- 24898897
TI  - What's new in paediatric extracorporeal membrane oxygenation?

PMID- 24898898
TI  - The upper cretaceous snake Dinilysia patagonica Smith-Woodward, 1901, and the
      crista circumfenestralis of snakes.
AB  - Studies on the phylogenetic relationships of snakes and lizards are plagued by
      problematic characterizations of anatomy that are then used to define characters
      and states in taxon-character matrices. State assignments and character
      descriptions must be clear characterizations of observable anatomy and
      topological relationships if homologies are to be hypothesized. A supposed
      homology among snakes, not observed in lizards, is the presence of a crista
      circumfenestralis (CCF), a system of bony crests surrounding the fenestra ovalis
      and lateral aperture of the recessus scalae tympani. We note that there are some
      fossil and extant snakes that lack a CCF, and some extant lizards that possess a
      morphological equivalent. The phylogenetically important upper Cretaceous fossil
      snake Dinilysia patagonica has been interpreted by different authors as either
      having or lacking a CCF. These conflicting results for Dinilysia were tested by
      re-examining the morphology of the otic region in a large sample of snakes and
      lizards. An unambiguous criterion arising from the test of topology is used to
      define the presence of a CCF: the enclosure of the ventral margin of the
      juxtastapedial recess by flanges of the otoccipital (crista tuberalis and crista
      interfenestralis) that extend forward to contact the posterior margin of the
      prootic. According to this criterion D. patagonica does not possess a CCF,
      therefore, this anatomical feature must have arisen later during the evolution of
      snakes.

PMID- 24898899
TI  - Influence of UGT1A1 6, 27, and 28 polymorphisms on nilotinib-induced
      hyperbilirubinemia in Japanese patients with chronic myeloid leukemia.
AB  - Nilotinib potently inhibits human uridine diphosphate-glucuronosyltransferase
      (UGT1A1) activity, causing hyperbilirubinemia. We investigated the influence of
      UGT1A1 polymorphisms and nilotinib plasma trough concentrations (C0) on nilotinib
      induced hyperbilirubinemia in 34 Japanese patients with chronic myeloid leukemia
      (CML). The proportion of patients with hyperbilirubinemia was significantly
      higher among patients with the UGT1A1*6/*6 and *6/*28 genotypes (poor
      metabolizers) than among those with other genotypes (p = 0.004). The median time
      to elevation of bilirubin levels in UGT1A1 poor metabolizers was 2.0 weeks
      (hazard ratio, 6.11). The median time to reduction in nilotinib dose in UGT1A1
      poor metabolizers was 4.0 weeks (hazard ratio, 7.52; p = 0.002). Consequently, in
      the maintenance phase 3 months following the initiation of nilotinib therapy, the
      median daily dose and C0 of nilotinib were 350 mg/day and 372 ng/mL,
      respectively, in UGT1A1 poor metabolizers, and 600 mg/day and 804 ng/mL,
      respectively, in the other patients. Patients at increased hyperbilirubinemia
      risk could be identified by prospective UGT1A1 genotyping prior to nilotinib
      therapy. To avoid an interruption of CML treatment due to nilotinib-induced
      hyperbilirubinemia, it may be beneficial to reduce the initial nilotinib dose to
      300-400 mg/day for UGT1A1 poor metabolizers. 

PMID- 24898900
TI  - Comprehensive endometrial immunoglobulin subclass analysis in infertile women
      suffering from repeated implantation failure with or without chronic
      endometritis.
AB  - PROBLEM: Chronic endometritis (CE) is a local inflammatory condition with unusual
      plasmacyte infiltration in the endometrial stromal area. CE is frequently found
      in infertile women with repeated implantation failure (RIF). In this study, we
      comprehensively investigated the endometrial immunoglobulin (Ig) subclass
      expression in infertile women suffering from RIF with versus without CE. METHOD
      OF STUDY: Endometrial biopsy specimens obtained from 28 infertile women with RIF
      and CE (the RIF-CE group), 23 infertile women with RIF but without CE (the RIF
      non-CE group), and 22 proven fertile women undergoing hysterectomy for benign
      endometrial pathology (the control group) were immunostained for Ig subclass
      expression. RESULTS: The density of IgM+, IgA1+, IgA2+, IgG1+, and IgG2+ stromal
      cells were significantly higher in the RIF-CE group than that in the RIF-non-CE
      and control group. The density of IgG2+ stromal cells was significantly higher
      than that of any other Ig subclass-positive cells (P<0.045) in the RIF-CE group.
      In serial section staining, the immunoreactivity for CD138 and Ig subclasses in
      the endometrial stroma was detectable in adjacent cells of some specimens in the
      RIF-CE group. CONCLUSIONS: The endometrium of infertile women with RIF-CE was
      characterized by increase in IgM, IgA, and IgG expression and predominance of
      IgG2 over other Ig subclasses.

PMID- 24898902
TI  - Neck thermography in the differentiation between diffuse toxic goiter during
      methimazole treatment and normal thyroid.

PMID- 24898904
TI  - In memoriam: Hitoshi Shirotani (1927-2014).

PMID- 24898903
TI  - Alpha-tubulin nuclear overexpression is an indicator of poor prognosis in
      patients with non-Hodgkin's lymphoma.
AB  - In the present study, the newly established mouse monoclonal antibody, Y-49,
      binding to a specific epitope of alpha-tubulin, was used to examine
      immunohistochemical reactivity in 116 patients with non-Hodgkin's lymphoma (NHL).
      The protein was detected at elevated levels in the nuclei of human proliferating
      cells by western blot analysis, flow cytometry and immunohistochemical analysis.
      The relatively weak binding in the cytoplasm was evident in almost all cases. The
      investigation of the correlation between immuno-histochemical positivity and
      clinicopathological variables revealed links with the MIB-1 proliferation index
      and poor survival. Nuclear positivity with Y-49 was more frequent in older-aged
      patients, those with nodal NHL and in those who harbored the diffuse large B-cell
      histological subtype, and was strongly associated with high MIB-1 labeling
      indices (LIs). Survival analysis by the Kaplan-Meier method revealed
      statistically significant differences between patients with high and low Y-49 LIs
      (p=0.0181), even in the group with advanced (stage III/IV) disease (p=0.0327).
      Multivariate analysis revealed that overexpression of alpha-tubulin is an
      independent prognostic factor in NHL with a relative risk of 2.786.

PMID- 24898905
TI  - Supervision and responses of psychiatry residents to adverse patient events.
AB  - OBJECTIVE: Throughout training, psychiatry residents may experience adverse
      patient outcomes. The purpose of this study was to explore whether residents'
      perceptions of the quality of their supervision impacts their emotional reactions
      to adverse events. METHODS: All psychiatry residents from a training program at
      an academic medical center who were in their PGY2-4 years, as well as those in
      their first year out of training, were recruited to participate. Those who self
      identified as having experienced an adverse event participated in a semi
      structured interview. For the purpose of the study, "adverse event" was defined
      as follows: patient suicide, patient homicide or homicide attempt outside the
      hospital, patient violence inside the hospital, life-threatening reaction to
      psychotropic medication, and physical assault of a resident by a patient.
      RESULTS: In this sample, 22 of the 64 residents (34 %) reported experiencing an
      adverse event. Of these, 21/22 (95 %) participated in the interview. Two
      residents reported experiencing two adverse events; the total number of adverse
      events analyzed was 23. For 21/23 (91 %) of these events, respondents felt that
      the quality of the supervision they received impacted their emotional reactions
      to the event. CONCLUSION: The supervisory relationship appears to play a
      significant role in how residents experience, and potentially learn from, adverse
      events; this has practical implications for educators and leaders.

PMID- 24898907
TI  - Rapid progression of pleural disease due to exposure to Libby amphibole: "Not
      your grandfather's asbestos related disease".
AB  - BACKGROUND: Residents and mine employees from Libby, Montana, have been exposed
      to asbestiform amphiboles from the vermiculite mine that operated in this
      location from the mid-1920s until 1990. Clinical observations show a different
      form of asbestos-related toxicity than other forms of asbestos. METHODS: Five
      illustrative cases from the Center for Asbestos-Related Diseases in Libby were
      selected. All had clear exposure histories, multiple follow-up visits,
      illustrative chest radiographic studies, serial pulmonary function tests, and
      sufficient length of follow-up to characterize disease progression. RESULTS:
      These cases developed increasing symptoms of dyspnea and chest pain, progressive
      radiological changes that were predominantly pleural, and a restrictive pattern
      of impaired spirometry that rapidly progressed with significant loss of pulmonary
      function. CONCLUSIONS: LA exposure can cause a non-malignant pleural disease that
      is more rapidly progressive and more severe than the usual asbestos-related
      disease.

PMID- 24898908
TI  - Visual search and emotion: how children with autism spectrum disorders scan
      emotional scenes.
AB  - This study assessed visual search abilities, tested through the flicker task, in
      children diagnosed with autism spectrum disorders (ASDs). Twenty-two children
      diagnosed with ASD and 22 matched typically developing (TD) children were told to
      detect changes in objects of central interest or objects of marginal interest
      (MI) embedded in either emotion-laden (positive or negative) or neutral real
      world pictures. The results showed that emotion-laden pictures equally interfered
      with performance of both ASD and TD children, slowing down reaction times
      compared with neutral pictures. Children with ASD were faster than TD children,
      particularly in detecting changes in MI objects, the most difficult condition.
      However, their performance was less accurate than performance of TD children just
      when the pictures were negative. These findings suggest that children with ASD
      have better visual search abilities than TD children only when the search is
      particularly difficult and requires strong serial search strategies. The
      emotional-social impairment that is usually considered as a typical feature of
      ASD seems to be limited to processing of negative emotional information. 

PMID- 24898909
TI  - Differences in the efficiency of pattern encoding in relation to autistic-like
      traits: an event-related potential study.
AB  - We examined the effects of complexity on the efficiency of pattern encoding in
      the general population differing on autism-spectrum quotient (AQ) scores. We
      compared brain activity (electroencephalography) during a same-different task for
      High and Low AQ groups. The task was composed of identical comparison and
      categorical comparison (CC) conditions that presented simple or complex patterns.
      In the CC condition, the Low AQ showed large P3b amplitudes with simple patterns
      than with complex patterns, whereas the High AQ showed the same amplitude levels
      for these patterns. These indicate that, similar to simple patterns, complex
      patterns are efficiently encoded in the High AQ. Moreover, the High AQ had no
      impairment in the global pattern encoding compared with the Low AQ. 

PMID- 24898910
TI  - Brief Report: A Pilot Summer Robotics Camp to Reduce Social Anxiety and Improve
      Social/Vocational Skills in Adolescents with ASD.
AB  - This pilot study evaluated a novel intervention designed to reduce social anxiety
      and improve social/vocational skills for adolescents with autism spectrum
      disorder (ASD). The intervention utilized a shared interest in robotics among
      participants to facilitate natural social interaction between individuals with
      ASD and typically developing (TD) peers. Eight individuals with ASD and eight TD
      peers ages 12-17 participated in a weeklong robotics camp, during which they
      learned robotic facts, actively programmed an interactive robot, and learned
      "career" skills. The ASD group showed a significant decrease in social anxiety
      and both groups showed an increase in robotics knowledge, although neither group
      showed a significant increase in social skills. These initial findings suggest
      that this approach is promising and warrants further study. 

PMID- 24898911
TI  - Are we under-estimating the association between autism symptoms?: The importance
      of considering simultaneous selection when using samples of individuals who meet
      diagnostic criteria for an autism spectrum disorder.
AB  - The magnitude of symptom inter-correlations in diagnosed individuals has
      contributed to the evidence that autism spectrum disorders (ASD) is a
      fractionable disorder. Such correlations may substantially under-estimate the
      population correlations among symptoms due to simultaneous selection on the areas
      of deficit required for diagnosis. Using statistical simulations of this
      selection mechanism, we provide estimates of the extent of this bias, given
      different levels of population correlation between symptoms. We then use real
      data to compare domain inter-correlations in the Autism Spectrum Quotient, in
      those with ASD versus a combined ASD and non-ASD sample. Results from both
      studies indicate that samples restricted to individuals with a diagnosis of ASD
      potentially substantially under-estimate the magnitude of association between
      features of ASD. 

PMID- 24898912
TI  - Electrical cell counting process characterization in a microfluidic impedance
      cytometer.
AB  - Particle counting in microfluidic devices with coulter principle finds many
      applications in health and medicine. Cell enumeration using microfluidic particle
      counters is fast and requires small volumes of sample, and is being used for
      disease diagnostics in humans and animals. A complete characterization of the
      cell counting process is critical for accurate cell counting especially in
      complex systems with samples of heterogeneous population interacting with
      different reagents in a microfluidic device. In this paper, we have characterized
      the electrical cell counting process using a microfluidic impedance cytometer.
      Erythrocytes were lysed on-chip from whole blood and the lysing was quenched to
      preserve leukocytes which subsequently pass through a 15 MUm * 15 MUm measurement
      channel used to electrically count the cells. We show that cell counting over
      time is a non-homogeneous Poisson process and that the electrical cell counts
      over time show the log-normal distribution, whose skewness can be attributed to
      diffusion of cells in the buffer that is used to meter the blood. We further
      found that the heterogeneous cell population (i.e. different cell types) shows
      different diffusion characteristics based on the cell size. Lymphocytes spatially
      diffuse more as compared to granulocytes and monocytes. The time difference
      between the cell occurrences follows an exponential distribution and when plotted
      over time verifies the cell diffusion characteristics. We also characterized the
      probability of occurrence of more than one cell at the counter within specified
      time intervals using Poisson counting statistics. For high cell concentration
      samples, we also derived the required sample dilution based on our particle
      counting characterization. Buffer characterization by considering the size based
      particle diffusion and estimating the required dilution are critical parameters
      for accurate counting results. 

PMID- 24898913
TI  - Spatial and temporal patterns in concentrations of perfluorinated compounds in
      bald eagle nestlings in the upper Midwestern United States.
AB  - Perfluorinated chemicals (PFCs) are of concern due to their widespread use,
      persistence in the environment, tendency to accumulate in animal tissues, and
      growing evidence of toxicity. Between 2006 and 2011 we collected blood plasma
      from 261 bald eagle nestlings in six study areas from the upper Midwestern United
      States. Samples were assessed for levels of 16 different PFCs. We used regression
      analysis in a Bayesian framework to evaluate spatial and temporal trends for
      these analytes. We found levels as high as 7370 ng/mL for the sum of all 16 PFCs
      (?PFCs). Perfluorooctanesulfonate (PFOS) and perfluorodecanesulfonate (PFDS) were
      the most abundant analytes, making up 67% and 23% of the PFC burden,
      respectively. Levels of ?PFC, PFOS, and PFDS were highest in more urban and
      industrial areas, moderate on Lake Superior, and low on the remote upper St.
      Croix River watershed. We found evidence of declines in ?PFCs and seven analytes,
      including PFOS, PFDS, and perfluorooctanoic acid (PFOA); no trend in two
      analytes; and increases in two analytes. We argue that PFDS, a long-chained PFC
      with potential for high bioaccumulation and toxicity, should be considered for
      future animal and human studies. 

PMID- 24898914
TI  - Genomic characterization of Salmonella Cerro ST367, an emerging Salmonella
      subtype in cattle in the United States.
AB  - BACKGROUND: Within the last decade, Salmonella enterica subsp. enterica serovar
      Cerro (S. Cerro) has become one of the most common serovars isolated from cattle
      and dairy farm environments in the northeastern US. The fact that this serovar is
      commonly isolated from subclinically infected cattle and is rarely associated
      with human disease, despite its frequent isolation from cattle, has led to the
      hypothesis that this emerging serovar may be characterized by reduced virulence.
      We applied comparative and population genomic approaches to (i) characterize the
      evolution of this recently emerged serovar and to (ii) gain a better
      understanding of genomic features that could explain some of the unique
      epidemiological features associated with this serovar. RESULTS: In addition to
      generating a de novo draft genome for one Salmonella Cerro strain, we also
      generated whole genome sequence data for 26 additional S. Cerro isolates,
      including 16 from cattle operations in New York (NY) state, 2 from human clinical
      cases from NY in 2008, and 8 from diverse animal sources (7 from Washington state
      and 1 from Florida). All isolates sequenced in this study represent sequence type
      ST367. Population genomic analysis showed that isolates from the NY cattle
      operations form a well-supported clade within S. Cerro ST367 (designated here "NY
      bovine clade"), distinct from isolates from Washington state, Florida and the
      human clinical cases. A molecular clock analysis indicates that the most recent
      common ancestor of the NY bovine clade dates back to 1998, supporting the recent
      emergence of this clone.Comparative genomic analyses revealed several relevant
      genomic features of S. Cerro ST367, that may be responsible for reduced virulence
      of S. Cerro, including an insertion creating a premature stop codon in sopA. In
      addition, patterns of gene deletion in S. Cerro ST367 further support adaptation
      of this clone to a unique ecological or host related niche. CONCLUSIONS: Our
      results indicate that the increase in prevalence of S. Cerro ST367 is caused by a
      highly clonal subpopulation and that S. Cerro ST367 is characterized by unique
      genomic deletions that may indicate adaptation to specific ecological niches and
      possibly reduced virulence in some hosts.

PMID- 24898916
TI  - Abdominal wall mass. Fungal mycetoma.

PMID- 24898917
TI  - Hepatocellular carcinoma with steatohepatitic features: a clinicopathological
      study of Japanese patients.
AB  - AIMS: The aim of this study was to investigate the clinicopathological
      significance of steatohepatitic features in hepatocellular carcinomas (HCCs)
      using a large-scale analysis. METHODS AND RESULTS: Retrospective
      clinicopathological analysis was performed on HCCs treated surgically at the
      University of Tokyo Hospital between 2005 and 2010. The diagnosis of HCC with
      steatohepatitic features (SH-HCC) was made if the tumour fulfilled four of the
      following five criteria: steatosis (>5% tumour cells), ballooning or Mallory-Denk
      body formation, interstitial fibrosis and inflammatory infiltrates. There were
      120 HCCs (31.4%) from 106 patients (36.3%) that met the criteria of SH-HCC.
      Patients with SH-HCC were characterized by a higher frequency of diabetes
      mellitus and hypertension, along with higher serum levels of cholesterol and
      triglycerides, than those with conventional HCC (P < 0.01). The background liver
      of SH-HCC patients showed steatosis and steatohepatitis more frequently (P <
      0.01). SH-HCCs were smaller, relatively more differentiated and had a higher
      frequency of bile duct invasion (P < 0.05). Multivariate analysis failed to show
      prognostic significance of steatohepatitic features in HCCs. CONCLUSIONS: SH-HCC
      is a subcategory of HCC associated with the patient's metabolic condition and the
      presence of steatosis or steatohepatitis in the background liver. Steatohepatitic
      features were not a significant prognostic factor for HCCs.

PMID- 24898915
TI  - Direct prediction of profiles of sequences compatible with a protein structure by
      neural networks with fragment-based local and energy-based nonlocal profiles.
AB  - Locating sequences compatible with a protein structural fold is the well-known
      inverse protein-folding problem. While significant progress has been made, the
      success rate of protein design remains low. As a result, a library of designed
      sequences or profile of sequences is currently employed for guiding experimental
      screening or directed evolution. Sequence profiles can be computationally
      predicted by iterative mutations of a random sequence to produce energy-optimized
      sequences, or by combining sequences of structurally similar fragments in a
      template library. The latter approach is computationally more efficient but
      yields less accurate profiles than the former because of lacking tertiary
      structural information. Here we present a method called SPIN that predicts
      Sequence Profiles by Integrated Neural network based on fragment-derived sequence
      profiles and structure-derived energy profiles. SPIN improves over the fragment
      derived profile by 6.7% (from 23.6 to 30.3%) in sequence identity between
      predicted and wild-type sequences. The method also reduces the number of residues
      in low complex regions by 15.7% and has a significantly better balance of
      hydrophilic and hydrophobic residues at protein surface. The accuracy of sequence
      profiles obtained is comparable to those generated from the protein design
      program RosettaDesign 3.5. This highly efficient method for predicting sequence
      profiles from structures will be useful as a single-body scoring term for
      improving scoring functions used in protein design and fold recognition. It also
      complements protein design programs in guiding experimental design of the
      sequence library for screening and directed evolution of designed sequences. The
      SPIN server is available at http://sparks-lab.org.

PMID- 24898919
TI  - Low free testosterone levels predict disease reclassification in men with
      prostate cancer undergoing active surveillance.
AB  - OBJECTIVE: To determine whether total testosterone and free testosterone levels
      predict disease reclassification in a cohort of men with prostate cancer (PCa) on
      active surveillance (AS). PATIENTS AND METHODS: Total testosterone and free
      testosterone concentrations were determined at the time the men began the AS
      protocol. Statistical analysis was performed using Student's t-test and a chi
      squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were obtained using univariate logistic regression. Receiver-operator
      characteristic curves were generated to determine the investigated testosterone
      thresholds. Kaplan-Meier curves were used to estimate time to disease
      reclassification. A Cox proportional hazard regression model was used for
      multivariate analysis. RESULTS: A total of 154 men were included in the AS
      cohort, of whom 54 (35%) progressed to active treatment. Men who had disease
      reclassification had significantly lower free testosterone levels than those who
      were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone
      levels <0.45 ng/dL had a higher rate of disease reclassification than patients
      with free testosterone levels >=0.45 (P = 0.032). Free testosterone levels <0.45
      ng/dL were associated with a several-fold increase in the risk of disease
      reclassification (OR 4.3, 95% CI 1.25-14.73). Multivariate analysis showed that
      free testosterone and family history of PCa were independent predictors of
      disease reclassification. CONCLUSIONS: Free testosterone levels were lower in men
      with PCa who had reclassification during AS. Men with moderately severe
      reductions in free testosterone level are at increased risk of disease
      reclassification.

PMID- 24898920
TI  - Complex thermal expansion properties in a molecular honeycomb lattice.
AB  - [FeL3][BF4]2.xH2O (L = 3-(pyrazinyl)-1H-pyrazole) shows negative thermal
      expansion between 150-240 K but positive thermal expansion at 240-300 K, linked
      to rearrangement of anions and water molecules within pores in the lattice. 

PMID- 24898918
TI  - Ewing sarcoma of the small bowel: a study of seven cases, including one with the
      uncommonly reported EWSR1-FEV translocation.
AB  - AIMS: Primary Ewing sarcoma of the ileum has rarely been documented. Little is
      known about its pathogenesis and clinical implications, and it would be helpful
      to identify novel molecular markers. EWSR1-FEV translocation is exceedingly rare
      in Ewing sarcoma, as FEV expression is restricted to prostate, brain and
      serotonin neuroendocrine cells (NE) and related tumours. METHODS AND RESULTS:
      Paraffin sections or snap-frozen material were used in this investigation.
      Tumours were investigated by means of immunohistochemistry, RT-PCR (EWSR1-FLI1,
      EWSR1-ERG and EWSR1-FEV transcripts), FISH analysis (EWSR1 break-apart and
      specific EWSR1-FEV translocation) and spectral karyotyping (SKY). Ten ileal
      neuroendocrine tumours (INET) made up the control group for EWSR1-FEV
      translocation. Among 445 Ewing sarcomas cases spanning a period of 20 years,
      seven (1.6%) arose in the ileum. All tumours were immunoreactive for
      synaptophysin, CD99, FLI1 and vimentin. FISH identified EWSR1 rearrangement in
      all cases, with EWSR1-FLI1 transcripts being detected in all but one tumour
      showing the uncommon EWSR1-FEV rearrangement, with SKY, RT-PCR and FISH
      confirmation. The mean survival of EWSR1-FLI1 patients was 14 months, whereas the
      EWSR1-FEV patient was alive after 15 years despite several recurrences controlled
      by surgery alone. No INET showed EWSR1 translocation. CONCLUSIONS: Most primary
      Ewing sarcomas of the ileum show the common EWSR1-FLI1 translocation, but EWSR1
      FEV could be specific for tumours arising in the ileum and showing better
      prognosis.

PMID- 24898922
TI  - Clinical significance of miR-126 in colorectal cancer.

PMID- 24898921
TI  - Attenuated brain-derived neurotrophic factor and hypertrophic remodelling: the
      SABPA study.
AB  - Brain-derived neurotrophic factor (BDNF) has been linked to neurological
      pathologies, but its role in cardiometabolic disturbances is limited. We aimed to
      assess the association between serum BDNF levels and structural endothelial
      dysfunction (ED) as determined by cross-sectional wall area (CSWA) and
      albumin/creatinine ratio (ACR) in black Africans. Ambulatory blood pressure (BP)
      and ultrasound CSWA values were obtained from 82 males and 90 females. Fasting
      blood and 8 h overnight urine samples were collected to determine serum BDNF and
      cardiometabolic risk markers, that is, glycated haemoglobin (HbA1c), lipids,
      inflammation and ACR. BDNF median split * gender interaction effects for
      structural ED justified stratification of BDNF into low and high (?/>1.37 ng ml(
      1)) gender groups. BDNF values (0.86-1.98 ng ml(-1)) were substantially lower
      than reference ranges (6.97-42.6 ng ml(-1)) in the African gender cohort,
      independent of age and body mass index. No relationship was revealed between BDNF
      and renal function and was opposed by an inverse relationship between BDNF and
      CSWA (r=-0.17; P=0.03) in the African cohort. Linear regression analyses revealed
      a positive relationship between systolic BP and structural remodelling in the
      total cohort and low-BDNF gender groups. In the high-BDNF females, HbA1C was
      associated with structural remodelling. Attenuated or possible downregulated BDNF
      levels were associated with hypertrophic remodelling, and may be a compensatory
      mechanism for the higher BP in Africans. In addition, metabolic risk and
      hypertrophic remodelling in women with high BDNF underpin different underlying
      mechanisms for impaired neurotrophin homeostasis in men and women. 

PMID- 24898923
TI  - Automated detection of cortical dysplasia type II in MRI-negative epilepsy.
AB  - OBJECTIVE: To detect automatically focal cortical dysplasia (FCD) type II in
      patients with extratemporal epilepsy initially diagnosed as MRI-negative on
      routine inspection of 1.5 and 3.0T scans. METHODS: We implemented an automated
      classifier relying on surface-based features of FCD morphology and intensity,
      taking advantage of their covariance. The method was tested on 19 patients (15
      with histologically confirmed FCD) scanned at 3.0T, and cross-validated using a
      leave-one-out strategy. We assessed specificity in 24 healthy controls and 11
      disease controls with temporal lobe epilepsy. Cross-dataset classification
      performance was evaluated in 20 healthy controls and 14 patients with
      histologically verified FCD examined at 1.5T. RESULTS: Sensitivity was 74%, with
      100% specificity (i.e., no lesions detected in healthy or disease controls). In
      50% of cases, a single cluster colocalized with the FCD lesion, while in the
      remaining cases a median of 1 extralesional cluster was found. Applying the
      classifier (trained on 3.0T data) to the 1.5T dataset yielded comparable
      performance (sensitivity 71%, specificity 95%). CONCLUSION: In patients initially
      diagnosed as MRI-negative, our fully automated multivariate approach offered a
      substantial gain in sensitivity over standard radiologic assessment. The proposed
      method showed generalizability across cohorts, scanners, and field strengths.
      Machine learning may assist presurgical decision-making by facilitating
      hypothesis formulation about the epileptogenic zone. CLASSIFICATION OF EVIDENCE:
      This study provides Class II evidence that automated machine learning of MRI
      patterns accurately identifies FCD among patients with extratemporal epilepsy
      initially diagnosed as MRI-negative.

PMID- 24898924
TI  - Frontal cortex BOLD signal changes in premanifest Huntington disease: a possible
      fMRI biomarker.
AB  - OBJECTIVE: To identify a possible functional imaging biomarker sensitive to the
      earliest neural changes in premanifest Huntington disease (preHD), allowing early
      therapeutic approaches aimed at preventing or delaying clinical onset. METHODS:
      Sixteen preHD and 18 healthy participants were submitted to anatomical
      acquisitions and functional MRI (fMRI) acquisitions during the execution of the
      exogenous covert orienting of attention task. Due to strong a priori hypothesis,
      all fMRI correlation analyses were restricted to the following: (1) the frontal
      oculomotor cortex identified by the means of a prosaccadic task, comprising
      frontal eye fields and supplementary frontal eye fields; and (2) the data
      collected during inhibition of return, a phenomenon occurring during the executed
      task. In preHD, multiple regression analysis was performed between fMRI data and
      the probability to develop the disease in the next 5 years (p5HD). Moreover, mean
      blood oxygen level-dependent (BOLD) signal changes in the frontal oculomotor
      cortex and striatal volumes were linearly correlated with p5HD. RESULTS: In
      preHD, multiple regression analysis showed that clusters of activity strongly
      correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean
      BOLD signal changes of this region correlated with p5HD (r(2) = 0.52). Among the
      considered striatal volumes, a modest correlation (r(2) = 0.29) was observed in
      the right putamen and p5HD. CONCLUSION: fMRI activations in the right-frontal
      oculomotor cortex during inhibition of return can be considered a possible
      functional imaging biomarker in preHD.

PMID- 24898926
TI  - Comment: has automated detection of cortical dysplasias come of age?

PMID- 24898925
TI  - Long-term safety and effectiveness of natalizumab redosing and treatment in the
      STRATA MS Study.
AB  - OBJECTIVES: Report long-term safety and effectiveness of natalizumab over 240
      weeks in the prospective, observational, open-label Safety of TYSABRI Re-dosing
      and Treatment (STRATA) Study. METHODS: Patients (N = 1,094) previously enrolled
      in natalizumab multiple sclerosis clinical trials received natalizumab 300 mg IV
      every 4 weeks, up to 240 weeks. Serious adverse events, Expanded Disability
      Status Scale (EDSS) scores, and annualized relapse rates were analyzed. RESULTS:
      At data cutoff (February 9, 2012), natalizumab exposure was 3,460 patient-years;
      a median of 56 (range 1-70) infusions were received. Serious adverse events,
      including progressive multifocal leukoencephalopathy, were consistent with
      natalizumab's known profile. Upon natalizumab re-exposure, rates of anti
      natalizumab antibodies and hypersensitivity reactions were 3% and 5% overall, and
      40% and 24% among patients with 1 to 2 prior natalizumab doses. Patients
      originally randomized to placebo/another disease-modifying therapy vs natalizumab
      in previous studies had significantly higher EDSS scores at STRATA baseline; this
      difference persisted over 240 weeks. EDSS scores generally remained stable.
      Patients initially randomized to natalizumab had lower annualized relapse rates
      over 240 weeks. CONCLUSIONS: Serious adverse events were consistent with
      natalizumab's known safety profile; short exposure with a gap before redosing was
      associated with higher incidences of anti-natalizumab antibodies and
      hypersensitivity reactions. Stability of EDSS scores and consistently low relapse
      rates over 5 years of natalizumab treatment are consistent with its known
      efficacy profile. CLASSIFICATION OF EVIDENCE: This study provides Class III
      evidence that in patients with relapsing-remitting multiple sclerosis,
      natalizumab stabilizes EDSS scores, decreases relapse rates, and is associated
      with an increased risk of progressive multifocal leukoencephalopathy.

PMID- 24898927
TI  - Comment: fMRI biomarker for premanifest HD?

PMID- 24898929
TI  - Disseminated giant porokeratosis and porokeratosis of Mibelli in Bankura and
      Bardhaman districts, West Bengal, India.
AB  - Porokeratosis of Mibelli (PM) is a rare genodermatosis. It is caused by
      proliferation of abnormal clones of epidermal cells in response to several
      stimuli, the most important of which is sunlight. Giant porokeratosis is thought
      to be a variant of PM. We report two cases of disseminated PM and one case of
      disseminated giant porokeratosis from the Bankura and Bardhaman districts of West
      Bengal in India; presenting to a single observer in the summer of 2012.
      Interestingly we have noted that the majority of cases of porokeratosis in India
      have been reported from West Bengal. Few patients with a single lesion of giant
      porokeratosis have been reported in world literature. As far as we know, this is
      the first case report of disseminated giant porokeratosis in world literature. 

PMID- 24898931
TI  - From basic to applied research to improve outcomes for individuals who require
      augmentative and alternative communication: potential contributions of eye
      tracking research methods.
AB  - In order to improve outcomes for individuals who require AAC, there is an urgent
      need for research across the full spectrum--from basic research to investigate
      fundamental language and communication processes, to applied clinical research to
      test applications of this new knowledge in the real world. To date, there has
      been a notable lack of basic research in the AAC field to investigate the
      underlying cognitive, sensory perceptual, linguistic, and motor processes of
      individuals with complex communication needs. Eye tracking research technology
      provides a promising method for researchers to investigate some of the visual
      cognitive processes that underlie interaction via AAC. The eye tracking research
      technology automatically records the latency, duration, and sequence of visual
      fixations, providing key information on what elements attract the individual's
      attention (and which ones do not), for how long, and in what sequence. As
      illustrated by the papers in this special issue, this information can be used to
      improve the design of AAC systems, assessments, and interventions to better meet
      the needs of individuals with developmental and acquired disabilities who require
      AAC (e.g., individuals with autism spectrum disorders, Down syndrome,
      intellectual disabilities of unknown origin, aphasia).

PMID- 24898928
TI  - Joint effect of mid- and late-life blood pressure on the brain: the AGES
      Reykjavik study.
AB  - OBJECTIVE: We hypothesized that in participants with a history of hypertension,
      lower late-life blood pressure (BP) will be associated with more brain pathology.
      METHODS: Participants are 4,057 older men and women without dementia with midlife
      (mean age 50 +/- 6 years) and late-life (mean age 76 +/- 5 years) vascular
      screening, cognitive function, and brain structures on MRI ascertained as part of
      the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. RESULTS: The
      association of late-life BP to brain measures depended on midlife hypertension
      history. Higher late-life systolic and diastolic BP (DBP) was associated with an
      increased risk of white matter lesions and cerebral microbleeds, and this was
      most pronounced in participants without a history of midlife hypertension. In
      contrast, in participants with a history of midlife hypertension, lower late-life
      DBP was associated with smaller total brain and gray matter volumes. This finding
      was reflected back in cognitive performance; in participants with midlife
      hypertension, lower DBP was associated with lower memory scores. CONCLUSION: In
      this large population-based cohort, late-life BP differentially affects brain
      pathology and cognitive performance, depending on the history of midlife
      hypertension. Our study suggests history of hypertension is critical to
      understand how late-life BP affects brain structure and function.

PMID- 24898930
TI  - Evaluation and treatment of migraine in the emergency department: a review.
AB  - Head pain is the fifth most common reason for emergency department (ED) visits.
      It is second only to focal weakness as the most common reason for neurological
      consultation in the ED. This manuscript reviews how patients with migraine, the
      most common primary headache disorder for which patients seek medical treatment,
      are managed in the ED. We discuss existing guidelines for head imaging in
      patients with migraine, recommended pharmacologic treatments, and current
      treatment trends. We also review studies evaluating the discharge care of
      migraine patients in the ED. With the goal of standardizing, streamlining, and
      optimizing ED-based migraine care, we offer ideas for future research to improve
      the evaluation, treatment, and discharge care of patients who present to an ED
      with acute migraine. 

PMID- 24898933
TI  - Deformability-based microfluidic cell pairing and fusion.
AB  - We present a microfluidic cell pairing device capable of sequential trapping and
      pairing of hundreds of cells using passive hydrodynamics and flow-induced
      deformation. We describe the design and operation principles of our device and
      show its applicability for cell fusion. Using our device, we achieved both
      homotypic and heterotypic cell pairing, demonstrating efficiencies up to 80%. The
      platform is compatible with fusion protocols based on biological, chemical and
      physical stimuli with fusion yields up to 95%. Our device further permits its
      disconnection from the fluidic hardware enabling its transportation for imaging
      and culture while maintaining cell registration on chip. Our design principles
      and cell trapping technique can readily be applied for different cell types and
      can be extended to trap and fuse multiple (>2) cell partners as demonstrated by
      our preliminary experiments. 

PMID- 24898934
TI  - [Should cases of hepatocellular carcinoma be discussed by non-specialized
      multidisciplinary team meetings?].
AB  - The treatment of hepatocellular carcinoma (HCC) is difficult due to the
      underlying cirrhosis which has its own influence on therapeutic issues. An
      inquiry was performed in centres with specialized multidisciplinary team meetings
      dedicated to HCC (HCC-MTM) or in centres with non-specialized (digestive oncology
      or general oncology) multidisciplinary team meetings (NS-MTM). The number of
      cases of HCCs taken in charge yearly was significantly higher in HCC-MTM than in
      NS-MTM (p=0,0014). Interventional radiologists and transplant surgeons were more
      frequently implied in HCC-MTM than in NS-MTM (respectively p=0,009 and p=0,02).
      On site availability of every treatment of HCC was higher in RCP-MTM than in NS
      MTM (p=0,015). There were no inclusion in clinical trials in 40.5 % of NS-MTM
      versus only 17.6 % of HCC-MTM (p=0,0086). In three clinical cases out of seven
      there were discrepancies between the therapeutic options of HCC-MTM and NS-MTM.
      In all three cases, the treatment offered to the patient by HCC-MTM was more
      consistent with clinical standards. These results prompt to perform more studies
      on the quality of management of patients with HCCs by MTMs.

PMID- 24898935
TI  - Quantitative scoring of differential drug sensitivity for individually optimized
      anticancer therapies.
AB  - We developed a systematic algorithmic solution for quantitative drug sensitivity
      scoring (DSS), based on continuous modeling and integration of multiple dose
      response relationships in high-throughput compound testing studies. Mathematical
      model estimation and continuous interpolation makes the scoring approach robust
      against sources of technical variability and widely applicable to various
      experimental settings, both in cancer cell line models and primary patient
      derived cells. Here, we demonstrate its improved performance over other response
      parameters especially in a leukemia patient case study, where differential DSS
      between patient and control cells enabled identification of both cancer-selective
      drugs and drug-sensitive patient sub-groups, as well as dynamic monitoring of the
      response patterns and oncogenic driver signals during cancer progression and
      relapse in individual patient cells ex vivo. An open-source and easily extendable
      implementation of the DSS calculation is made freely available to support its
      tailored application to translating drug sensitivity testing results into
      clinically actionable treatment options. 

PMID- 24898936
TI  - First 100 laparoscopic surgeries in a predominantly rural Nigerian population: a
      template for future growth.
AB  - BACKGROUND: Minimal access surgery has revolutionized surgery practice. Its
      proven advantages, such as reduced postoperative pain, early return to
      unrestricted activities, and better cosmesis, have become important drivers for
      its rapid development. In sub-Saharan Africa this development has been slow. The
      aim of the current study was to describe the challenges and outcomes of
      laparoscopic procedures in a public hospital that caters to a predominantly rural
      population. MATERIAL AND METHODS: The first 100 patients who underwent
      laparoscopic procedure in the Department of Surgery at Federal Medical Centre,
      Owerri, Nigeria were retrospectively analyzed. Data were retrieved from the
      medical records department as well as the surgical theater procedure register.
      The focus of the study was on patient demographics, indication for surgery,
      procedure performed, length of hospital stay, and morbidity and mortality data.
      Staff training was done locally and abroad. RESULTS: Altogether, 100 patients had
      laparoscopic surgery in our general surgery unit from September 2007 through July
      2013. The ages of the patients was 5-75 years (median 36.5 years). The three main
      procedures were cholecystectomy (36 %), diagnostic laparoscopy (29 %), and
      appendectomy (21 %). The other operations performed included liver abscess
      drainage (7 %), adhesiolysis (3 %), hernia repair (1 %), and Heller's myotomy (1
      %). Four cases were converted to open surgery. There were no deaths. There were
      14 grades I and II postoperative complications in nine patients. CONCLUSIONS: Our
      study suggests that basic laparoscopic procedures could be offered safely to our
      resource-poor rural population. It is a platform on which we can hopefully
      introduce advanced laparoscopic surgical operations.

PMID- 24898937
TI  - Lanthanide-based functional misfit-layered nanotubes.
AB  - The synthesis of nanotubes from layered compounds has generated substantial
      scientific interest. "Misfit" layered compounds (MLCs) of the general formula
      [(MX)(1+x)](m)[TX2]n, where M can include Pb, Sb, rare earths; T=Cr, Nb, and X=S,
      Se can form layered structures, even though each sub-system alone is not
      necessarily a layered or a stable compound. A simple chemical method is used to
      synthesize these complex nanotubes from lanthanide-based misfit compounds.
      Quaternary nanotubular structures formed by partial substitution of the
      lanthanide atom in nanotubes by other elements are also confirmed. The driving
      force and mechanism of formation of these nanotubes is investigated by systematic
      temperature and time-dependent studies. A stress-inducement mechanism is proposed
      to explain the formation of the nanotubes. The resulting materials may find
      applications in fields that include thermoelectrics, light emitters, and
      catalysis and address fundamental physical issues in low dimensions.

PMID- 24898938
TI  - Atom-based 3D-QSAR, molecular docking and molecular dynamics simulation
      assessment of inhibitors for thyroid hormone receptor alpha and beta.
AB  - The three-dimensional quantitative structure-activity relationship (3D-QSAR) for
      inhibitors of thyroid hormone receptors (TR) alpha and (TR) beta was studied. The
      training set of the TRalpha model generated a correlation coefficient (R(2)) = 
      0.9535, with standard deviation (SD) =  0.3016. From the test set of the TRalpha
      model, a Q(2) value for the predicted activities (= 0.4303), squared correlation
      (random selection R(2)-CV  =  0.6929), Pearson-R (= 0.7294) and root mean square
      error (RMSE  =  0.6342) were calculated. The P-value for TRalpha (= 1.411e-96)
      and TRbeta (= 2.108e-165) models indicate a high degree of self-reliance. For the
      TRbeta model, the training set yielded R(2) = 0.9424 with SD = 0.3719. From the
      test set of TRbeta, Q(2) value (= 0.5336), the squared correlation (R(2)-CV  = 
      0.7201), the Pearson-R (= 0.7852) and RMSE for test set predictions (= 0.8630)
      all strengthen the good predictive competence of the QSAR model derived.
      Examination of internal as well as external validation supports the rationality
      and good predictive ability of the best model. Molecular docking explained the
      conformations of molecules and important amino acid residues at the docking
      pocket, and a molecular dynamics simulation study further uncovered the binding
      process and validated the rationality of docking results. The findings not only
      lead to a better understanding of interactions between these antagonists and
      thyroid hormone receptors alpha and beta, but also provide valuable information
      about the impact of structure on activity that will be very beneficial in the
      design of novel antagonists with preferred activity.

PMID- 24898940
TI  - Theoretical study of CO oxidation on cationic, neutral, and anionic AuM dimers (M
      = Pd and Ag).
AB  - The CO and O2 adsorption as well as CO oxidation on cationic, neutral, and
      anionic AuM dimers (M = Pd, Ag) are studied by density functional calculations.
      Our results show that CO and O2 are adsorbed more stably on AuPd dimers than on
      AuAg dimers with corresponding charge state. O2 is favorable to be adsorbed on Pd
      atom in AuPd(+), AuPd and AuPd(-) dimers. CO is adsorbed on Pd in AuPd and AuPd(
      ), while it is favorable to be adsorbed on Au in AuPd(+). For AuAg dimers, O2 is
      adsorbed on Ag in AuAg and AuAg(-), and it is adsorbed on Au in AuAg(+). CO is
      adsorbed on Ag in AuPd(-), while it is adsorbed on Au in AuAg and AuAg(+). The CO
      oxidation reaction is explored along two possible pathways: path-1 involves CO
      attacking the initial complexes of AuM dimers and O2, and path-2 is related to O2
      interacting with the complexes of AuM dimers and CO. The charge state of AuM
      dimers has a substantial effect on CO oxidation. The reaction on AuPd(-) prefers
      path-1, and AuPd(+) mediated reaction proceeds along path-2, while CO oxidation
      on AuPd is difficult along both paths. For AuAg, both pathways are viable for
      AuAg(-) mediated reactions, while AuAg and AuAg(+) mediated reactions prefer path
      2. Moreover, the energy barriers of CO oxidation on neutral AuAg is comparable
      with those on AuPd in all charge states while the energy barriers for AuAg(-) and
      AuAg(+) are considerably lower than those for all AuPd dimmers, indicating the
      impurity atom also plays a significant role in the catalytic activity.
      Furthermore, AuAg(-) is proposed to be the most active species due to the lowest
      barrier involved in the reaction. 

PMID- 24898941
TI  - Anarchic hand with abnormal agency following right inferior parietal lobe damage:
      a case report.
AB  - Anarchic hand syndrome (AHS) is characterized by goal-directed movements
      performed without volitional control (agency). Different AHS subtypes have been
      identified; however, few studies have examined the posterior subtype. We report a
      case of AHS following right-hemisphere parietal damage, with left-sided
      somatosensory and proprioceptive impairment. Agency was examined for nonanarchic
      (volitional) movements performed using the anarchic hand. The patient experienced
      abnormal agency for movements whether motor intention and visual feedback were
      congruent or incongruent, but not when intention was absent (passive movement).
      Findings suggest a general disturbance of veridical motor awareness and agency in
      this case of parietal AHS. 

PMID- 24898939
TI  - Structures of TraI in solution.
AB  - Bacterial conjugation, a DNA transfer mechanism involving transport of one
      plasmid strand from donor to recipient, is driven by plasmid-encoded proteins.
      The F TraI protein nicks one F plasmid strand, separates cut and uncut strands,
      and pilots the cut strand through a secretion pore into the recipient. TraI is a
      modular protein with identifiable nickase, ssDNA-binding, helicase and protein
      protein interaction domains. While domain structures corresponding to roughly 1/3
      of TraI have been determined, there has been no comprehensive structural study of
      the entire TraI molecule, nor an examination of structural changes to TraI upon
      binding DNA. Here, we combine solution studies using small-angle scattering and
      circular dichroism spectroscopy with molecular Monte Carlo and molecular dynamics
      simulations to assess solution behavior of individual and groups of domains.
      Despite having several long (>100 residues) apparently disordered or highly
      dynamic regions, TraI folds into a compact molecule. Based on the biophysical
      characterization, we have generated models of intact TraI. These data and the
      resulting models have provided clues to the regulation of TraI function. 

PMID- 24898942
TI  - Promotora Outreach, Education and Navigation Support for HPV Vaccination to
      Hispanic Women with Unvaccinated Daughters.
AB  - Cervical cancer disparities persist in the predominantly Hispanic population of
      South Texas, and Hispanic girls are less likely to initiate and complete the
      three-dose human papillomavirus (HPV) vaccine series. Culturally relevant
      interventions are needed to eliminate these disparities and improve HPV vaccine
      initiation and completion. We enrolled 372 Hispanic women from South Texas'
      Cameron and Hidalgo counties with a daughter, aged 11-17, who had not received
      HPV vaccine. All participants received an HPV vaccine educational brochure in
      their preferred language (English or Spanish) and were invited to participate in
      the Entre Madre e Hija (EMH) program, a culturally relevant cervical cancer
      prevention program. EMH participants (n = 257) received group health education,
      referral and navigation support from a promotora (a trained, culturally competent
      community health worker). Those who declined participation in EMH received the
      brochure only (n = 115). Eighty-four percent of enrolled participants initiated
      the HPV vaccine, and no differences were observed between EMH program and
      brochure-only participants. Compared to brochure-only participants, EMH
      participants were more likely to complete the vaccine series [adjusted odds ratio
      (adj. OR) = 2.24, 95% CI (1.25, 4.02)]. In addition, participants who were
      employed and insured had lower odds of completing the vaccine series [adj. OR =
      0.45, 95% CI (0.21-0.96); adj. OR = 0.36, 95% CI (0.13-0.98), respectively]. All
      enrolled participants had high vaccine initiation rates (>80%); however, EMH
      program participants were more likely to complete the vaccine series. HPV vaccine
      promotion efforts that include referral and navigation support in addition to
      education show promise.

PMID- 24898943
TI  - Mapping polarization induced surface band bending on the Rashba semiconductor
      BiTeI.
AB  - Surfaces of semiconductors with strong spin-orbit coupling are of great interest
      for use in spintronic devices exploiting the Rashba effect. BiTeI features large
      Rashba-type spin splitting in both valence and conduction bands. Either can be
      shifted towards the Fermi level by surface band bending induced by the two
      possible polar terminations, making Rashba spin-split electron or hole bands
      electronically accessible. Here we demonstrate the first real-space microscopic
      identification of each termination with a multi-technique experimental approach.
      Using spatially resolved tunnelling spectroscopy across the lateral boundary
      between the two terminations, a previously speculated on p-n junction-like
      discontinuity in electronic structure at the lateral boundary is confirmed
      experimentally. These findings realize an important step towards the exploitation
      of the unique behaviour of the Rashba semiconductor BiTeI for new device concepts
      in spintronics. 

PMID- 24898947
TI  - Getting into the colon: approaches to target colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most common cancer in the world and the
      second most common cause of cancer related deaths. Conventional treatment of CRC
      is comprised of drug (chemotherapeutic agents) administration by parenteral
      route, which delivers the drug to both normal as well as cancerous tissues, thus
      leading to numerous undesirable effects. Enormous research is going on worldwide
      for designing an alternative route of administration, among which oral colon
      targeted drug delivery systems have gained immense attention amongst scientific
      community. Direct delivery of drugs at the site of action leads to an increase in
      the availability of drugs at the targeted region. This causes a reduction in the
      amount of drug required to exert same therapeutic effect, thus reducing the
      incidents of adverse effects. Various maneuvers (pH-dependent, time-dependent and
      microflora-activated systems) have been attempted by researchers for targeting
      drugs successfully to the colonic region by circumventing the upper part of
      gastrointestinal tract. This Editorial article aims to put forth an overview of
      the formulation technologies that have been developed for attaining colon
      specific drug delivery for the treatment of CRC. 

PMID- 24898948
TI  - Epigenetic alterations in endocrine-related cancer.
AB  - Aberrant epigenetics is a hallmark of cancer, and endocrine-related tumors are no
      exception. Recent research has been identifying an ever-growing number of
      epigenetic alterations in both genomic DNA methylation and histone post
      translational modification in tumors of the endocrine system. Novel microarray
      and ultra-deep sequencing technologies have allowed the identification of genome
      wide epigenetic patterns in some tumor types such as adrenocortical, parathyroid,
      and breast carcinomas. However, in other cancer types, such as the multiple
      endocrine neoplasia syndromes and thyroid cancer, tumor information is limited to
      candidate genes alone. Future research should fill this gap and deepen our
      understanding of the functional role of these alterations in cancer, as well as
      defining their possible clinical uses.

PMID- 24898946
TI  - Filifactor alocis: The Newly Discovered Kid on the Block with Special Talents.
AB  - Infection-induced periodontal disease has been primarily focused on a small group
      of periodontal pathogens. A paradigm shift, based on data emerging from the oral
      microbiome project, now suggests the involvement of as-yet-unculturable and
      fastidious organisms. Collectively, these studies have demonstrated that there
      are changes in the periodontal status associated with shifts in the composition
      of the bacterial community in the periodontal pocket. In addition, it is likely
      that the emerging new pathogens may play a more significant role in the disease.
      One of the organisms previously unrecognized is Filifactor alocis. While this
      Gram-positive anaerobic rod has been identified in peri-implantitis, in
      endodontic infections, and in patients with localized aggressive periodontitis,
      its presence is now observed at significantly higher levels in patients with
      adult periodontitis or refractory periodontitis. Its colonization properties and
      its potential virulence attributes support the proposal that F. alocis should be
      included as a diagnostic indicator of periodontal disease. Moreover, these
      emerging characteristics would be consistent with the polymicrobial synergy and
      dysbiosis (PSD) periodontal pathogenesis model. Here, unique characteristics of
      F. alocis are discussed. F. alocis has specific factors that can modulate
      multiple changes in the microbial community and host cell proteome. It is likely
      that such variations at the molecular level are responsible for the functional
      changes required to mediate the pathogenic process. 

PMID- 24898949
TI  - Leadership and teamwork in medical emergencies: performance of nursing students
      and registered nurses in simulated patient scenarios.
AB  - AIMS AND OBJECTIVES: To examine nursing students' and registered nurses' teamwork
      skills whilst managing simulated deteriorating patients. BACKGROUND: Studies
      continue to show the lack of timely recognition of patient deterioration.
      Management of deteriorating patients can be influenced by education and
      experience. DESIGN: Mixed methods study conducted in two universities and a rural
      hospital in Victoria, and one university in Queensland, Australia. METHODS: Three
      simulation scenarios (chest pain, hypovolaemic shock and respiratory distress)
      were completed in teams of three by 97 nursing students and 44 registered nurses,
      equating to a total of 32 student and 15 registered nurse teams. Data were
      obtained from (1) Objective Structured Clinical Examination rating to assess
      performance; (2) Team Emergency Assessment Measure scores to assess teamwork; (3)
      simulation video footage; (4) reflective interview during participants' review of
      video footage. Qualitative thematic analysis of video and interview data was
      undertaken. RESULTS: Objective structured clinical examination performance was
      similar across registered nurses and students (mean 54% and 49%); however, Team
      Emergency Assessment Measure scores differed significantly between the two groups
      (57% vs 38%, t = 6.841, p < 0.01). In both groups, there was a correlation
      between technical (Objective Structured Clinical Examination) and nontechnical
      (Team Emergency Assessment Measure) scores for the respiratory distress scenario
      (student teams: r = 0.530, p = 0.004, registered nurse teams r = 0.903, p < 0.01)
      and hypovolaemia scenario (student teams: r = 0.534, p = 0.02, registered nurse
      teams: r = 0.535, p = 0.049). Themes generated from the analysis of the combined
      quantitative and qualitative data were as follows: (1) leadership and
      followership behaviours; (2) help-seeking behaviours; (3) reliance on previous
      experience; (4) fixation on a single detail; and (5) team support. CONCLUSIONS:
      There is scope to improve leadership, team work and task management skills for
      registered nurses and nursing students. Simulation appears to be beneficial in
      enabling less experienced staff to assess their teamwork skills. RELEVANCE TO
      CLINICAL PRACTICE: There is a need to encourage less experienced staff to become
      leaders and for all staff to develop improved teamwork skills for medical
      emergencies.

PMID- 24898951
TI  - Two Fe3(MU3-S)2(CO)8 clusters with terminal N-heterocyclic carbenes.
AB  - The title compounds with terminal N-heterocyclic carbenes, namely
      octacarbonyl(imidazolidinylidene-kappaC(2))di-MU3-sulfido-triiron(II)(2 Fe-Fe),
      [Fe3(C3H6N2)(MU3-S)2(CO)8], (I), and octacarbonyl(1-methylimidazo[1,5-a]pyridin-3
      ylidene-kappaC(3))di-MU3-sulfido-triiron(II)(2 Fe-Fe), [Fe3(C8H8N2)(MU3
      S)2(CO)8], (II), have been synthesized. Each compound contains two Fe-Fe bonds
      and two S atoms above and below a triiron triangle. One of the eight carbonyl
      ligands deviates significantly from linearity. In (I), dimers generated by an N
      H...S hydrogen bond are linked into [001] double chains by a second N-H...S
      hydrogen bond. These chains are packed by a C-H...O hydrogen bond to yield [101]
      sheets. In (II), dimers generated by an N-H...S hydrogen bond are linked by C
      H...O hydrogen bonds to form [111] double chains.

PMID- 24898950
TI  - Qualitative study of the feasibility of HPV vaccine delivery to young adolescent
      girls in Vietnam: evidence from a government-implemented demonstration program.
AB  - BACKGROUND: Introduction of human papillomavirus (HPV) vaccine in national
      programs has proceeded apace since 2006, mostly in high-income countries.
      Recently concluded pilots of HPV vaccination in low-income countries have
      provided important lessons learned for these settings; however, rigorous
      evaluations of the feasibility of these delivery strategies that effectively
      reach young adolescents have been few. This paper presents results from a
      qualitative evaluation of a demonstration program which implemented school-based
      and health center-based HPV vaccinations to all girls in grade 6, or 11 years of
      age, for two years in four districts of Vietnam. METHODS: Using semi-structured
      interviews of 131 health and education staff from local, district, province, and
      national levels and 26 focus-group discussions with local project implementers (n
      = 153), we conducted a qualitative two-year evaluation to measure the impact of
      HPV vaccinations on the health and education systems. RESULTS: HPV vaccine
      delivery at schools or health centers was made feasible by: a. close
      collaboration between the health and education sectors, b. detailed planning for
      implementation, c. clearly defined roles and responsibilities for project
      implementers, d. effective management and supervision of vaccinations during
      delivery, and e. engagement with community organizations for support. Both the
      health and education systems were temporarily challenged with the extra workload,
      but the disruptions were short-lived (a few days for each of three doses) and
      perceived as worth the longer-term benefit of cervical cancer prevention.
      CONCLUSION: The learning from Vietnam has identified critical elements for
      successful vaccine delivery that can provide a model for other countries to
      consider during their planning of national rollout of HPV vaccine.

PMID- 24898952
TI  - Redetermination of NaGdS2, NaLuS2 and NaYS2.
AB  - The title structures NaGdS2 (sodium gadolinium sulfide), NaLuS2 (sodium lutetium
      sulfide) and NaYS2 (sodium yttrium sulfide) were redetermined in order to improve
      the structural information available for the family of group 1 and thallium rare
      earth sulfides, which are isostructural with the rhombohedral alpha-NaFeO2
      structure type. In particular, the present investigation has been directed at the
      rhombohedral sodium rare earth sulfides. The observed dependence of the
      fractional coordinate z(S(2-)) on the identity of the rare earth element in the
      newly determined structures is in agreement with the known structures of the
      potassium and rubidium analogues. Crystals of NaGdS2 and NaLuS2 display obverse
      reverse twinning. 

PMID- 24898954
TI  - Two nickel(II) bis[(pyridin-2-yl)methyl]amine complexes with homophthalic and
      benzene-1,2,4,5-tetracarboxylic acids.
AB  - Two new Ni(II) complexes involving the ancillary ligand bis[(pyridin-2
      yl)methyl]amine (bpma) and two different carboxylate ligands, i.e. homophthalate
      [hph; systematic name: 2-(2-carboxylatophenyl)acetate] and benzene-1,2,4,5
      tetracarboxylate (btc), namely catena-poly[[aqua{bis[(pyridin-2-yl)methyl]amine
      kappa(3)N,N',N''}nickel(II)]-MU-2-(2-carboxylatophenyl)aceteto-kappa(2)O:O'],
      [Ni(C9H6O4)(C12H13N3)(H2O)]n, and (MU-benzene-1,2,4,5-tetracarboxylato
      kappa(4)O(1),O(2):O(4),O(5))bis(aqua{bis[(pyridin-2-yl)methyl]amine
      kappa(3)N,N',N''}nickel(II)) bis(triaqua{bis[(pyridin-2-yl)methyl]amine
      kappa(3)N,N',N''}nickel(II)) benzene-1,2,4,5-tetracarboxylate hexahydrate,
      [Ni2(C10H2O8)(C12H13N3)2(H2O)2].[Ni(C12H13N3)(H2O)3]2(C10H2O8).6H2O, (II), are
      presented. Compound (I) is a one-dimensional polymer with hph acting as a
      bridging ligand and with the chains linked by weak C-H...O interactions. The
      structure of compound (II) is much more complex, with two independent Ni(II)
      centres having different environments, one of them as part of centrosymmetric
      [Ni(bpma)(H2O)]2(btc) dinuclear complexes and the other in mononuclear
      [Ni(bpma)(H2O)3](2+) cations which (in a 2:1 ratio) provide charge balance for
      btc(4-) anions. A profuse hydrogen-bonding scheme, where both coordinated and
      crystal water molecules play a crucial role, provides the supramolecular linkage
      of the different groups.

PMID- 24898953
TI  - (8RS)-4-Amino-6-(4-chlorophenyl)-8-(2,4-dichlorothiazol-5-yl)-8,9-dihydro-7H
      pyrimido[4,5-b][1,4]diazepine N,N-dimethylformamide monosolvate: sheets built
      from N-H...N and C-H...O hydrogen bonds.
AB  - In the title compound, C16H11Cl3N6S.C3H7NO, the seven-membered ring adopts a
      conformation which is close to the twist-boat form. The molecular components are
      linked into sheets by a combination of two N-H...N hydrogen bonds and two C-H...O
      hydrogen bonds. Comparisons are made with other aminopyrimidine derivatives.

PMID- 24898955
TI  - 2,2'-Bi[benzo[b]thiophene]: an unexpected isolation of the benzo[b]thiophene
      dimer.
AB  - The crystal structure of 2,2'-bi[benzo[b]thiophene], C16H10S2, at 173 K has
      triclinic (P1) symmetry. It is of interest with respect to its apparent mode of
      synthesis, as it is a by-product of a Stille cross-coupling reaction in which it
      was not explictly detected by spectroscopic methods. It was upon crystal
      structure analysis of a specimen isolated from the mother liquor that this
      reaction was determined to give rise to the title compound, which is a dimer
      arising from the starting material. Two independent half-molecules of this dimer
      comprise the asymmetric unit, and the full molecules are generated via inversion
      centers. Both molecules in the unit cell exhibit ring disorder, and they are
      essentially identical because of their rigidity and planarity.

PMID- 24898956
TI  - A new semiconducting quaternary mixed halogenide: pentathallium dimercury
      pentabromide tetraiodide, Tl5Hg2Br5I4.
AB  - A novel quaternary mixed halogenide, Tl5Hg2Br5I4, was synthesized by fusion of
      thallium bromide and mercury iodide in a 5:2 molar ratio. The crystal structure
      of Tl5Hg2Br5I4 represents a new series of composite structures described by the
      general formula nTlBr*mTl2[HgBr2I2]; in this case, n = 4 and m = 8. Electronic
      structure calculations indicate that the title compound is a semiconductor. 

PMID- 24898957
TI  - Folded conformations due to arene interactions in dissymmetric and symmetric
      butylidene-linker models based on pyrazolo[3,4-d]pyrimidine, purine and 7
      deazapurine.
AB  - The butylidene-linker models 1-[2-(2,6-dimethylsulfanyl-9H-purin-9-yl)-2
      methylidenepropyl]-4,6-bis(methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine,
      C18H20N8S4, (XI), 7,7'-(2-methylidenepropane-1,3-diyl)bis[3-methyl-2
      methylsulfanyl-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one], C20H22N6O2S2, (XIV), and 7
      [2-(4,6-dimethylsulfanyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylidenepropyl]-3
      methyl-2-methylsulfanyl-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one, C19H21N7OS3, (XV),
      show folded conformations in solution, as shown by (1)H NMR analysis. This
      folding carries over to the crystalline state. Intramolecular pi-pi interactions
      are observed in all three compounds, but only (XIV) shows additional
      intramolecular C-H...pi interactions in the solid state. As far as can be
      established, this is the first report incorporating the pyrrolo[2,3-d]pyrimidine
      nucleus for such a study. In addition to the pi-pi interactions, the crystal
      structures are also stabilized by other weak intermolecular C-H...S/N/O and/or
      S...N/S interactions.

PMID- 24898958
TI  - A novel dinuclear bismuth(III) coordination compound: bis(MU-pyridine-2,6
      dicarboxylato)-kappa4O2,N,O6:O6';kappa4O2:O2',N,O6-bis[(azido-kappaN)(1,10
      phenanthroline-kappa2N,N')bismuth(III)] tetrahydrate.
AB  - A novel dinuclear bismuth(III) coordination compound,
      [Bi2(C7H3NO4)2(N3)2(C12H8N2)2].4H2O, has been synthesized by an ionothermal
      method and characterized by elemental analysis, energy-dispersive X-ray
      spectroscopy, IR, X-ray photoelectron spectroscopy and single-crystal X-ray
      diffraction. The molecular structure consists of one centrosymmetric dinuclear
      neutral fragment and four water molecules. Within the dinuclear fragment, each
      Bi(III) centre is seven-coordinated by three O atoms and four N atoms. The
      coordination geometry of each Bi(III) atom is distorted pentagonal-bipyramidal
      (BiO3N4), with one azide N atom and one bridging carboxylate O atom located in
      axial positions. The carboxylate O atoms and water molecules are assembled via O
      H...O hydrogen bonds, resulting in the formation of a three-dimensional
      supramolecular structure. Two types of pi-pi stacking interactions are found,
      with centroid-to-centroid distances of 3.461 (4) and 3.641 (4) A.

PMID- 24898959
TI  - Molecular and supramolecular ionic aggregates H(x)O(y)(z) in organic and
      organometallic crystalline hydrates.
AB  - Ionic aggregates of the form H(x)O(y)(z) (z ? 0) have been characterized during
      an analysis of 245 crystal structures extracted from the Cambridge Structural
      Database [Allen (2002). Acta Cryst. B58, 380-388]. A systematic nomenclature is
      proposed for these species. Three modes of hydrogen bonding are described,
      characterized in part by the distance between contiguous O atoms: normal (NHB;
      O...O = 2.6-3.0 A), charge assisted (CAHB; O...O = 2.5 A) and molecular (MHB;
      O...O = 2.4 A). The three modes are consistent with previous reports, our
      experimental results, and quantum-chemical-optimized geometries and energetics.
      No evidence is presented concerning the possible existence or stability of these
      aggregates in solution. Rather, emphasis is placed on the necessity in crystal
      structure analysis to develop thoroughly existing hydrogen-bonded networks,
      ignorance of which can lead to erroneous crystal structure models and other
      physico-chemical data associated with composition and charge balance.

PMID- 24898961
TI  - Hydrogen ADPs with Cu Kalpha data? Invariom and Hirshfeld atom modelling of
      fluconazole.
AB  - For the structure of fluconazole [systematic name: 2-(2,4-difluorophenyl)-1,3
      bis(1H-1,2,4-triazol-1-yl)propan-2-ol] monohydrate, C13H12F2N6O.H2O, a case study
      on different model refinements is reported, based on single-crystal X-ray
      diffraction data measured at 100 K with Cu Kalpha radiation to a resolution of
      sin theta/lambda of 0.6 A(-1). The structure, anisotropic displacement parameters
      (ADPs) and figures of merit from the independent atom model are compared to
      'invariom' and 'Hirshfeld atom' refinements. Changing from a spherical to an
      aspherical atom model lowers the figures of merit and improves both the accuracy
      and the precision of the geometrical parameters. Differences between results from
      the two aspherical-atom refinements are small. However, a refinement of ADPs for
      H atoms is only possible with the Hirshfeld atom density model. It gives
      meaningful results even at a resolution of 0.6 A(-1), but requires good low-order
      data. 

PMID- 24898960
TI  - Substituent effects in trans-p,p'-disubstituted azobenzenes: X-ray structures at
      100 K and DFT-calculated structures.
AB  - The crystal and molecular structures of two para-substituted azobenzenes with pi
      electron-donating -NEt2 and pi-electron-withdrawing -COOEt groups are reported,
      along with the effects of the substituents on the aromaticity of the benzene
      ring. The deformation of the aromatic ring around the -NEt2 group in N,N,N',N'
      tetraethyl-4,4'-(diazenediyl)dianiline, C20H28N4, (I), may be caused by steric
      hindrance and the pi-electron-donating effects of the amine group. In this
      structure, one of the amine N atoms demonstrates clear sp(2)-hybridization and
      the other is slightly shifted from the plane of the surrounding atoms. The
      molecule of the second azobenzene, diethyl 4,4'-(diazenediyl)dibenzoate,
      C18H18N2O4, (II), lies on a crystallographic inversion centre. Its geometry is
      normal and comparable with homologous compounds. Density functional theory (DFT)
      calculations were performed to analyse the changes in the geometry of the studied
      compounds in the crystalline state and for the isolated molecules. The most
      significant changes are observed in the values of the N=N-C-C torsion angles,
      which for the isolated molecules are close to 0.0 degrees . The HOMA (harmonic
      oscillator model of aromaticity) index, calculated for the benzene ring,
      demonstrates a slight decrease of the aromaticity in (I) and no substantial
      changes in (II). 

PMID- 24898962
TI  - A novel alkaline earth strontium(II) coordination polymer:
      poly[hexaaquatetrakis(MU5-pyridine-2,6-dicarboxylato)bis(MU4-pyridine-2,6
      dicarboxylato)(MU7-sulfato)heptastrontium(II)].
AB  - The title compound, [Sr7(C7H3NO4)6(SO4)(H2O)6]n, has been synthesized by an
      ionothermal method using the ionic liquid 1-ethyl-3-methylimidazolium ([Emim]Br)
      as solvent, and characterized by elemental analysis, energy-dispersive X-ray
      spectroscopy, IR and single-crystal X-ray diffraction. The structure of the
      compound can be viewed as a three-dimensional coordination polymer composed of
      Sr(2+) cations, pyridine-2,6-dicarboxylate anions, sulfate anions and water
      molecules. The compound not only exhibits a three-dimensional structure with a
      unique coordination mode of the sulfate anion, but also features the first
      example of a heptanuclear strontium(II) coordination polymer. The structure is
      further stabilized by O-H...O hydrogen bonds and pi-pi stacking interactions.

PMID- 24898963
TI  - Preparation and X-ray analysis of potassium (2,3-dichlorophenyl)glucosinolate.
AB  - There has been much interest in obtaining crystals for crystallographic analysis
      of biologically active glucosinolates. Crystals of potassium (2,3
      dichlorophenyl)glucosinolate were obtained as a dual solvate, containing one
      methanol and one ethanol molecule of crystallization, K(+).C13H14Cl2NO9S2(
      ).CH3OH.C2H5OH. The three-dimensional polymeric network consists of chains
      containing the potassium ions coordinated and bridged by sugar O atoms, which run
      parallel to the a axis and are further crosslinked through the sugar molecules.
      The channels of this network are occupied by the dichlorophenyl substituents and
      the ethanol and methanol solvent molecules. The structure of the S-(2,3,4,6-tetra
      O-acetyl-beta-D-glucopyranosyl)-2,3-dichlorophenylacetothiohydroxymate,
      C21H23Cl2NO10S, precursor has also been determined and the beta-configuration and
      Z isomer of the thiohydroximate substituent is confirmed. 

PMID- 24898964
TI  - Fe(III) in a low-spin state in caesium bis[3-ethoxysalicylaldehyde 4
      methylthiosemicarbazonato(2-)-kappa3O2,N1,S]ferrate(III) methanol monosolvate.
AB  - The synthesis and crystal structure (at 100 K) of the title compound,
      Cs[Fe(C11H13N3O2S2)2].CH3OH, is reported. The asymmetric unit consists of an
      octahedral [Fe(III)(L)2](-) fragment, where L(2-) is 3-ethoxysalicylaldehyde 4
      methylthiosemicarbazonate(2-) {systematic name: [2-(3-ethoxy-2
      oxidobenzylidene)hydrazin-1-ylidene](methylamino)methanethiolate}, a caesium
      cation and a methanol solvent molecule. Each L(2-) ligand binds through the
      thiolate S, the imine N and the phenolate O atoms as donors, resulting in an
      Fe(III)S2N2O2 chromophore. The O,N,S-coordinating ligands are orientated in two
      perpendicular planes, with the O and S atoms in cis positions and the N atoms in
      trans positions. The Fe(III) cation is in the low-spin state at 100 K. 

PMID- 24898965
TI  - A copper(I) coordination polymer incorporation the corrosion inhibitor 1H
      benzotriazole: poly[MU3-benzotriazolato-kappa(3)N(1):N(2):N(3)-copper(I)].
AB  - The title complex, [Cu(C6H4N3)]n, was synthesized by the reaction of cupric
      nitrate, 1H-benzotriazole (BTAH) and aqueous ammonia under hydrothermal
      conditions. The asymmetric unit contains three crystallographically independent
      Cu(I) cations and two 1H-benzotriazolate ligands. Two of the Cu(I) cations, one
      with a linear two-coordinated geometry and one with a four-coordinated
      tetrahedral geometry, are located on sites with crystallographically imposed
      twofold symmetry. The third Cu(I) cation, with a planar three-coordinated
      geometry, is on a general position. Two Cu(I) cations are doubly bridged by two
      BTA(-) ligands to afford a noncentrosymmetric planar [Cu2(BTA)2] subunit, and two
      [Cu2(BTA)2] subunits are arranged in an antiparallel manner to form a
      centrosymmetric [Cu2(BTA)2]2 secondary building unit (SBU). The SBUs are
      connected in a crosswise manner via the sharing of four-coordinated Cu(I)
      cations, Cu-N bonding and bridging by two-coordinate Cu(I) cations, resulting in
      a one-dimensional chain along the c axis. These one-dimensional chains are
      further linked by C-H...pi and weak van der Waals interactions to form a three
      dimensional supramolecular architecture.

PMID- 24898967
TI  - Two-dimensional coordination polymeric structures in caesium complexes with ring
      substituted phenoxyacetic acids.
AB  - The two-dimensional polymeric structures of the caesium complexes with the
      phenoxyacetic acid analogues (4-fluorophenoxy)acetic acid, (3-chloro-2
      methylphenoxy)acetic acid and the herbicidally active (2,4-dichlorophenoxy)acetic
      acid (2,4-D), namely poly[[MU5-(4-fluorophenoxy)acetato][MU4-(4
      fluorophenoxy)acetato]dicaesium], [Cs2(C8H6FO3)2]n, (I), poly[aqua[MU5-(3-chloro
      2-methylphenoxy)acetato]caesium], [Cs(C9H8ClO3)(H2O)]n, (II), and poly[[MU7-(2,4
      dichlorophenoxy)acetato][(2,4-dichlorphenoxy)acetic acid]caesium],
      [Cs(C8H5Cl2O3)(C8H6Cl2O3)]n, (III), are described. In (I), the Cs(+) cations of
      the two individual irregular coordination polyhedra in the asymmetric unit (one
      CsO7 and the other CsO8) are linked by bridging carboxylate O-atom donors from
      the two ligand molecules, both of which are involved in bidentate chelate
      Ocarboxy,Ophenoxy interactions, while only one has a bidentate carboxylate O,O'
      chelate interaction. Polymeric extension is achieved through a number of
      carboxylate O-atom bridges, with a minimum Cs...Cs separation of 4.3231 (9) A,
      giving layers which lie parallel to (001). In hydrated complex (II), the
      irregular nine-coordination about the Cs(+) cation comprises a single monodentate
      water molecule, a bidentate Ocarboxy,Ophenoxy chelate interaction and six
      bridging carboxylate O-atom bonding interactions, giving a Cs...Cs separation of
      4.2473 (3) A. The water molecule forms intralayer hydrogen bonds within the two
      dimensional layers, which lie parallel to (100). In complex (III), the irregular
      centrosymmetric CsO6Cl2 coordination environment comprises two O-atom donors and
      two ring-substituted Cl-atom donors from two hydrogen bis[(2,4
      dichlorophenoxy)acetate] ligand species in a bidentate chelate mode, and four O
      atom donors from bridging carboxyl groups. The duplex ligand species lie across
      crystallographic inversion centres, linked through a short O-H...O hydrogen bond
      involving the single acid H atom. Structure extension gives layers which lie
      parallel to (001). The present set of structures of Cs salts of phenoxyacetic
      acids show previously demonstrated trends among the alkali metal salts of simple
      benzoic acids with no stereochemically favourable interactive substituent groups
      for formation of two-dimensional coordination polymers.

PMID- 24898966
TI  - An organic-inorganic hybrid compound containing imidazolium cations and a one
      dimensional lithium hexacyanidocobaltate-based anionic framework.
AB  - An organic-inorganic hybrid compound, catena-poly[bis(3H-imidazol-1-ium)
      [[tetracyanido-kappa(4)C-cobalt(III)]-MU-cyanido-kappa(2)C:N-[diaqualithium(I)]
      MU-cyanido-kappa(2)N:C]], {(C3H5N2)2[CoLi(CN)6(H2O)2]}n, was synthesized by the
      reaction of Li3[Co(CN)6] with imidazolium chloride in aqueous solution. The
      compound crystallizes in the monoclinic space group C2/c (data collected at 273
      K). In the crystal structure, neighbouring [Co(CN)6](3-) anionic units are linked
      by Li(+) cations through the cyanide groups in a trans mode, forming a one
      dimensional zigzag chain structure extending along the c axis. A three
      dimensional supramolecular network is formed through hydrogen-bonding
      interactions and is further stabilized by weak CN...pi interactions between the
      cyanide groups and the imidazolium cations.

PMID- 24898968
TI  - A new three-dimensional coordination polymer of Sr(II) based on dipicolinic acid,
      with different coordination environments for Sr(II).
AB  - A three-dimensional coordination polymer of Sr(II) based on dipicolinic acid
      (pydcH2) has been synthesized and characterized, namely poly[[diaquabis(MU3-6
      carboxypyridine-2-carboxylato)bis(MU4-pyridine-2,6
      dicarboxylato)tristrontium(II)] dihydrate],
      {[Sr3(C7H3NO4)2(C7H4NO4)2(H2O)2].2H2O}n. The asymmetric unit consists of two
      unique Sr(II) centres (one of them situated on an inversion centre), two
      independent pydc(2-) ligands, and one coordinated and one uncoordinated water
      molecule. The two independent Sr(II) cations are surrounded by water and
      dipicolinate molecules in distorted square-antiprism and distorted tricapped
      trigonal prismatic geometries. The dipicolinate ligands adopt MU3- and MU4
      bridging modes, linking the alkaline earth metal centres into a three-dimensional
      coordination framework. One dipicolinate ligand is doubly deprotonated, while the
      other is singly deprotonated. 

PMID- 24898969
TI  - Octyl 1-(5-tert-butyl-1H-pyrazol-3-yl)-2-(4-chlorophenyl)-1H-benzimidazole-5
      carboxylate: complex sheets built from N-H...N, C-H...N and C-H...O hydrogen
      bonds.
AB  - In the title compound, C29H35ClN4O2, the bond lengths provide evidence for
      aromatic delocalization in the pyrazole ring but bond fixation in the fused
      imidazole ring, and the octyl chain is folded, rather than adopting an all-trans
      chain-extended conformation. A combination of N-H...N, C-H...N and C-H...O
      hydrogen bonds links the molecules into sheets, in which the hydrogen bonds
      occupy the central layer with the tert-butyl and octyl groups arranged on either
      side, such that the closest contacts between adjacent sheets involve only the
      octyl groups. Comparisons are made with the supramolecular assembly in some
      simpler analogues.

PMID- 24898970
TI  - The Ce2Li0.39Ni1.61Si2 structure as a new derivative of the AlB2 family.
AB  - A new quaternary dicerium lithium/nickel disilicide, Ce2Li0.39Ni1.61Si2,
      crystallizes as a new structure type of intermetallic compounds closely related
      to the AlB2 family. The crystal-chemical interrelationships between parent AlB2
      type, BaLiSi, ZrBeSi and the title compound are discussed using the Barnighausen
      formalism. Two Ce atoms occupy sites of 3m. symmetry. The remainder, i.e. Ni,
      mixed Ni/Li and Si atoms, occupy sites of -6m2 symmetry. The environment of the
      Ce atom is an 18-vertex polyhedron and the Ni, Ni/Li and Si atoms are enclosed in
      tricapped trigonal prisms. The title structure can be assigned to class No. 10
      (trigonal prism and its derivatives) according to the Krypyakevich classification
      scheme [Krypyakevich (1977). In Structure Types of Intermetallic Compounds.
      Moscow: Nauka]. The electronic structure of the title compound was calculated
      using the tight-binding linear muffin-tin orbital method in the atomic spheres
      approximation (TB-LMTO-ASA). Metallic bonding is dominant in this compound. The
      strongest interactions are Ni-Si and Ce-Si. 

PMID- 24898971
TI  - An ethanol-solvated centrosymmetric dimer of bismuth(III) and thiosaccharinate
      resulting from 'semicoordination' contacts.
AB  - In the title compound, bis(MU-1,1-dioxo-1,2-benzothiazole-3-thiolato)
      kappa(3)N,S:S;kappa(3)S:N,S-bis[(1,1-dioxo-1,2-benzothiazole-3-thiolato
      kappa(2)N,S)(ethanol-kappaO)bismuth(III)] ethanol hemisolvate,
      [Bi2(C7H4NO2S2)6(C2H5OH)2].0.5C2H5OH, three independent thiosaccharinate (tsac)
      anions chelate the metal centre through the endocyclic N and exocyclic S atoms.
      The complex also presnts two 'semicoordination' contacts, one from a pendant
      ethanol solvent molecule and a second one from an S atom of a centrosymmetrically
      related molecule. This latter interaction complements two pi-pi interactions
      between tsac rings to form a dimeric entity which is the elemental unit that
      builds up the crystal structure. These dinuclear units are connected to each
      other via a second type of pi-pi interaction, generating chains along [111]. Two
      ethanol molecules, one of them of full occupancy at a general position and
      semicoordinated to the central cation, and a second one depleted and disordered
      around a symmetry centre, stabilize the structure. The complex was studied
      theoretically and the vibrational assignations were confirmed by employing
      theoretical density functional theory (DFT) methods.

PMID- 24898972
TI  - Formation of lithium, sodium and potassium complexes with 1,3,5-triamino-1,3,5
      trideoxy-cis-inositol (taci).
AB  - Single crystals of (1,3-diamino-5-azaniumyl-1,3,5-trideoxy-cis-inositol
      kappa(3)O(2),O(4),O(6))(1,3,5-triamino-1,3,5-trideoxy-cis-inositol
      kappa(3)O(2),O(4),O(6))lithium(I) diiodide dihydrate,
      [Li(C6H16N3O3)(C6H15N3O3)]I2.2H2O or [Li(Htaci)(taci)]I2.2H2O (taci is 1,3,5
      triamino-1,3,5-trideoxy-cis-inositol), (I), bis(1,3,5-triamino-1,3,5-trideoxy-cis
      inositol-kappa(3)O(2),O(4),O(6))sodium(I) iodide, [Na(C6H15N3O3)2]I or
      [Na(taci)2]I, (II), and bis(1,3,5-triamino-1,3,5-trideoxy-cis-inositol
      kappa(3)O(2),O(4),O(6))potassium(I) iodide, [K(C6H15N3O3)2]I or [K(taci)2]I,
      (III), were grown by diffusion of MeOH into aqueous solutions of the complexes.
      The structures of the Na and K complexes are isotypic. In all three complexes,
      the taci ligands adopt a chair conformation with axial hydroxy groups, and the
      metal cations exhibit exclusive O-atom coordination. The six O atoms of the
      resulting MO6 unit define a centrosymmetric trigonal antiprism with approximate
      D3d symmetry. The interligand O...O distances increase significantly in the order
      Li < Na < K. The structure of (I) exhibits a complex three-dimensional network of
      R-NH2-H...NH2-R, R-O-H...NH2-R and R-O-H...O(H)-H...NH2-R hydrogen bonds. The
      structures of the Na and K complexes consist of a stack of layers, in which each
      taci ligand is bonded to three neighbours via pairwise O-H...NH2 interactions
      between vicinal HO-CH-CH-NH2 groups.

PMID- 24898973
TI  - Effects of impaired renal function on levels and performance of D-dimer in
      patients with suspected pulmonary embolism.
AB  - Clinical probability and D-dimer measurement play an essential role in the non
      invasive diagnostic strategies for pulmonary embolism (PE). PE can be ruled out
      without further imaging in patients with non-high clinical probability and
      negative D-dimer. D-dimer level is increased in patients with renal impairment.
      Whether its diagnostic usefulness is maintained in these patients is not well
      determined. We aimed to evaluate the effects of renal impairment on diagnostic
      performances of D-dimer in patients with suspected PE. A retrospective analysis
      of 1,625 patients with suspected PE included in a multicentre prospective study
      was performed. D-dimer levels and percentages of patients with a negative D-dimer
      were compared between three subgroups according to glomerular filtration rate
      (GFR) estimated by the MDRD formula: >=90 ml/min (normal renal function), 60-89
      ml/min (mild renal impairment), 30-59 ml/min (moderate renal impairment). D-dimer
      levels increased and the proportion of negative D-dimer decreased significantly
      according to renal status: 46% negative D-dimer in patients with normal GFR, 31%
      in patients with mild renal impairment, 11% in those with moderate renal
      impairment, corresponding to number of patients needed to test to obtain one
      negative test of 2.2, 3.2 and 9, respectively. In conclusion, the clinical
      usefulness of D-dimer decreases with renal impairment. However, PE can still be
      ruled out by negative D-dimer in a substantial proportion of patients with non
      high clinical probability, avoiding exposure to contrast media. 

PMID- 24898975
TI  - Calixarene-based chemosensors by means of click chemistry.
AB  - Click chemistry, a new strategy for organic chemistry, has been widely used in
      the chemical modification of calixarenes because of its reliability, specificity,
      biocompatibility, and efficiency. Click-derived triazoles also play a critical
      role in sensing ions and molecules. This in-depth review provides an overview of
      calixarene-based chemosensors that incorporate click-derived triazoles, and their
      three characteristics (chromogenic, fluorescence, and wettability) are reviewed. 

PMID- 24898976
TI  - Phase transition of a perovskite strongly coupled to the vacuum field.
AB  - The hysteresis and dynamics of the phase transition of the perovskite salt
      [Pb(II)I4(2-),(C12H25NH3(+))2] is shown to be significantly modified when
      strongly coupled to the vacuum field inside a micro-cavity. The transition
      barrier is increased and the hysteresis loop is enlarged, demonstrating the
      potential of controlling the electromagnetic environment of a material.

PMID- 24898978
TI  - Latent tuberculosis infection in psoriasis and other dermatological
      immunomediated diseases: a combined approach by QuantiFERON-TB Gold and
      tuberculin skin tests.

PMID- 24898977
TI  - A single codon insertion in PICALM is associated with development of familial
      subvalvular aortic stenosis in Newfoundland dogs.
AB  - Familial subvalvular aortic stenosis (SAS) is one of the most common congenital
      heart defects in dogs and is an inherited defect of Newfoundlands, golden
      retrievers and human children. Although SAS is known to be inherited, specific
      genes involved in Newfoundlands with SAS have not been defined. We hypothesized
      that SAS in Newfoundlands is inherited in an autosomal dominant pattern and
      caused by a single genetic variant. We studied 93 prospectively recruited
      Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac
      screening evaluations for Newfoundlands we conducted a pedigree evaluation,
      genome-wide association study and RNA sequence analysis to identify a proposed
      pattern of inheritance and genetic loci associated with the development of SAS.
      We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding
      clathrin assembly protein (PICALM) that is associated with the development of SAS
      in Newfoundlands. Pedigree evaluation best supported an autosomal dominant
      pattern of inheritance and provided evidence that equivocally affected
      individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated
      the presence of PICALM in the canine myocardium and area of the subvalvular
      ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis
      resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus
      laevis embryos. The ability to test for presence of this PICALM insertion may
      impact dog-breeding decisions and facilitate reduction of SAS disease prevalence
      in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid
      in future molecular and genetic investigations into other congenital heart
      defects of various species. 

PMID- 24898979
TI  - MiR-5000-3p, miR-5009-3P and miR-552: potential microRNA biomarkers of side
      population cells in colon cancer.
AB  - Colon cancer is one of the most common cancers in the world. Multidrug resistance
      is related to poor prognosis of advanced colon cancer. The side population plays
      an important role in multiple drug resistance (MDR) of colon cancer. MicroRNA
      biomarkers of the side population of colon cancer is still unknown. In the
      present study, we aimed to explore miRNA markers of side population (SP) cells of
      colon cancer. The side population was sorted by flow cytometry. Cell viability
      was measured using an MTT assay. MicroRNA profiling analysis was performed to
      compare microRNA expression levels in the SP cells of colon cancer with levels in
      the non-SP cells of colon cancer. RT-PCR was applied to verify the result
      obtained from the microRNA profiling analysis. miR-5000-3p, miR-5009-3P and miR
      552 were all found to be upregulated in SP cells of the colon cancer cell lines
      HCT-15, HT-29 and LoVo. RT-PCR confirmed the result from the microRNA profiling
      analysis. This implied that miR-5000-3p, miR-5009-3P and miR-552 may be potential
      microRNA biomarkers of the side population in colon cancer, which may provide new
      specific targets of the side population for the reversal of MDR of colon cancer. 

PMID- 24898980
TI  - Tinea nigra presenting speckled or "salt and pepper" pattern.
AB  - A 7-year-old Caucasian female resident of the southern coast of Brazil presented
      dark spots on the left palm that converged to a unique macule with speckled
      pattern at about 1 month. The mycological exam and the fungi culture were typical
      of Hortaea werneckii, the agent of the superficial mycosis Tinea nigra. The
      patient received butenafine hydrochloride 1% for 30 days, resulting in a complete
      remission of the lesion. At a follow-up visit 12 months after treatment, there
      was no lesion recurrence. We describe a form of rare geographical Tinea nigra
      with a speckled pattern. The "salt and pepper" aspect should be taken into
      consideration when the mycosis was suspected. 

PMID- 24898981
TI  - Topical paromomycin and gentamicin for new world cutaneous leishmaniasis in
      Panama.

PMID- 24898982
TI  - In response.

PMID- 24898983
TI  - Unilateral clubbing as a clinical manifestation of lower limb venous
      malformation.

PMID- 24898984
TI  - Ultra-high-pressure homogenization (UHPH) system for producing high-quality
      vegetable-based beverages: physicochemical, microbiological, nutritional and
      toxicological characteristics.
AB  - BACKGROUND: A relatively new technology based on a continuous system of ultra
      high-pressure homogenization (UHPH) was used for producing high-quality soy and
      almond beverages as an alternative to conventional heat treatments
      (pasteurization and UHT). The aim of this study was to compare those treatments
      by analyzing the most relevant quality parameters with a broad vision from the
      production to the potential toxicological changes, passing through the main
      nutritional characteristics. RESULTS: UHPH treatment at 200 MPa, 55  degrees C
      T(in) produced a higher reduction of microorganisms than pasteurization. UHPH
      treatment at 300 MPa, 75  degrees C T(in) led to complete inactivation of
      microorganisms, similar to UHT treatment. A much better colloidal stability was
      observed in both UHPH-treated almond and soy beverages compared with those
      processed by conventional heat treatments. UHPH treatments led to the same
      increase in digestibility as heat treatments and did not produce a reduction in
      the availability of lysine. In addition, UHPH samples of soy beverage seem to be
      less allergenic based on their lower gut immune response in comparison with heat
      treated samples. CONCLUSION: UHPH treatments could be used to produce high
      quality commercial vegetable beverages with different quality standards (fresh or
      long-life storage) according to consumer preference.

PMID- 24898985
TI  - Anticancer patent landscape and technology assessment of Indian public-funded
      research institutes and organizations.
AB  - INTRODUCTION: This review discusses the various drug therapeutic targets and
      latest technologies of anticancer patents from 10 Indian public-funded research
      organizations covering more than 150 esteemed institutes. We have identified and
      reported the leading assignee and inventors along with their collaboration
      network and, thereby, have analyzed the various patent trends, geographical
      distributions, citation maps, Derwent World Patents Index, international patent
      classification analysis and the like. AREAS COVERED: This article provides the
      insights of 1905 patent documents from 191 families and discusses in-depth
      anticancer technology through categorization studies at the level of drug
      discovery, drug development and treatment and diagnosis. In addition, various
      cancer targets were correlated with recent technologies so as to identify the
      white spaces for upcoming technologies. EXPERT OPINION: Over a period of 13 years
      (1990 - 2013) the main focus of Indian cancer research was in the field of
      synthetic chemistry and natural extracts followed by the pharmaceutical
      compositions and combinations, whereas, the white spaces for future cancer remedy
      were identified from research in the areas of cancer stem cell lines, vaccines,
      gene therapy, nano formulations with targeted drug delivery systems as core and
      latest technologies.

PMID- 24898986
TI  - Comorbidity profiles and inpatient outcomes during hospitalization for heart
      failure: an analysis of the U.S. Nationwide inpatient sample.
AB  - BACKGROUND: Treatment of heart failure (HF) is particularly complex in the
      presence of comorbidities. We sought to identify and associate comorbidity
      profiles with inpatient outcomes during HF hospitalizations. METHODS: Latent
      mixture modeling was used to identify common profiles of comorbidities during
      adult hospitalizations for HF from the 2009 Nationwide Inpatient Sample (n =
      192,327). RESULTS: Most discharges were characterized by "common" comorbidities.
      A "lifestyle" profile was characterized by a high prevalence of uncomplicated
      diabetes, hypertension, chronic pulmonary disorders and obesity. A "renal"
      profile had the highest prevalence of renal disease, complicated diabetes, and
      fluid and electrolyte imbalances. A "neurovascular" profile represented the
      highest prevalence of cerebrovascular disease, paralysis, myocardial infarction
      and peripheral vascular disease. Relative to the common profile, the lifestyle
      profile was associated with a 15% longer length of stay (LOS) and 12% greater
      cost, the renal profile was associated with a 30% higher risk of death, 27%
      longer LOS and 24% greater cost, and the neurovascular profile was associated
      with a 45% higher risk of death, 34% longer LOS and 37% greater cost (all p <
      0.001). CONCLUSIONS: Comorbidity profiles are helpful in identifying adults at
      higher risk of death, longer length of stay, and accumulating greater costs
      during hospitalizations for HF.

PMID- 24898988
TI  - Partial-slip frictional response of rough surfaces.
AB  - If two elastic bodies with rough surfaces are first pressed against each other
      and then loaded tangentially, sliding will occur at the boundary of the contact
      area while the inner parts may still stick. With increasing tangential force, the
      sliding parts will expand while the sticking parts shrink and finally vanish. In
      this paper, we study the fractions of the contact area, tangential force and
      tangential stiffness, associated with the sticking portion of the contact area,
      as a function of the total applied tangential force up to the onset of full
      sliding. For the numerical analysis randomly rough, fractal surfaces are used,
      with the Hurst exponent H ranging from 0.1 to 0.9. Numerical simulations by
      boundary element method are compared with an analytical analysis in the framework
      of the Greenwood and Williamson (GW) model. In both cases, a universal linear
      dependency between the real contact area fraction in stick condition and the
      applied tangential force is found, regardless of the Hurst exponent of the rough
      surfaces. Regarding the dependence of the differential tangential stiffness on
      the tangential force, a linear relation is found in the GW case. For randomly
      rough surfaces, a nonlinear relation depending on H is derived. 

PMID- 24898989
TI  - Full-length coding sequences of two MICA alleles, MICA*002:01 and MICA*012:01,
      identified by sequence-based typing in Chinese individuals.
AB  - Full-length coding sequences of MICA*002:01 and MICA*012:01, were identified by
      sequence-based typing in Chinese individuals. 

PMID- 24898987
TI  - Trial to re-evaluate ultrasound in the treatment of tibial fractures (TRUST): a
      multicenter randomized pilot study.
AB  - BACKGROUND: The role of low-intensity pulsed ultrasound (LIPUS) in the management
      of fractures remains controversial. The purpose of this study was to assess the
      feasibility of a definitive trial to determine the effect of LIPUS on functional
      and clinical outcomes in tibial fractures managed operatively. METHODS: We
      conducted a multicenter, concealed, blinded randomized trial of 51 skeletally
      mature adults with operatively managed tibial fractures who were treated with
      either LIPUS or a sham device. All participating centers were located in Canada
      and site investigators were orthopedic surgeons specializing in trauma surgery.
      The goals of our pilot study were to determine recruitment rates in individual
      centers, investigators' ability to adhere to study protocol and data collection
      procedures, our ability to achieve close to 100% follow-up rates, and the degree
      to which patients were compliant with treatment. Patients were followed for one
      year and a committee (blinded to allocation) adjudicated all outcomes. The
      committee adjudicators were experienced (10 or more years in practice) orthopedic
      surgeons with formal research training, specializing in trauma surgery. RESULTS:
      Our overall rate of recruitment was approximately 0.8 patients per center per
      month and site investigators successfully adhered to the study protocol and
      procedures. Our rate of follow-up at one year was 84%. Patient compliance,
      measured by an internal timer in the study devices, revealed that 39 (76%) of the
      patients were fully compliant and 12 (24%) demonstrated a greater than 50%
      compliance. Based on patient feedback regarding excessive questionnaire burden,
      we conducted an analysis using data from another tibial fracture trial that
      revealed the Short Musculoskeletal Function Assessment (SMFA) dysfunction index
      offered no important advantages over the SF-36 Physical Component Summary (PCS)
      score. No device-related adverse events were reported. CONCLUSIONS: Our pilot
      study identified key issues that might have rendered a definitive trial
      unfeasible. By modifying our protocol to address these challenges we have
      enhanced the feasibility of a definitive trial to explore the effect of LIPUS on
      tibial fracture healing. TRIAL REGISTRATION: The TRUST definitive trial was
      registered at ClinicalTrials.gov on 21 April 2008 (identifier: NCT00667849).

PMID- 24898991
TI  - [Catheter ablation for the treatment of electrical storm: methods and outcome].
AB  - Electrical storm imposes a negative effect on quality of life and increases
      patient mortality. Once antiarrhythmic drug therapy proves ineffective, catheter
      ablation becomes the therapy of choice. The preferred procedural endpoint
      following catheter ablation of ES is defined as lack of inducibility of any
      clinical or non-clinical ventricular arrhythmia. If successful, catheter ablation
      of ES can significantly lower patient mortality. 

PMID- 24898992
TI  - Eating seeds from the 'be still' tree, yet having lucky nut poisoning: a case of
      acute yellow oleander poisoning.
AB  - A 25-year-old woman was evaluated and treated for ingestion of Thevetia peruviana
      seeds and flower petals-a natural digoxin cross reacting cardinolide-with intent
      to cause self-harm. The following case report provides the clinical presentation,
      treatment and management of acute yellow oleander poisoning. 

PMID- 24898990
TI  - [Electrical storm in the emergency room: clinical pathways].
AB  - In patients with structural heart disease, occurrence of an electrical storm (ES)
      is associated with increased mortality acutely and during medium term follow-up.
      Depending on the underlying heart disease and baseline type of arrhythmia,
      different clinical pathways have to be followed to reach sustained freedom from
      ventricular arrhythmia recurrences. Trigger elimination, sympathetic blockade
      (initially using betablockers and sedation), antiarrhythmic therapy with
      amiodarone and catheter ablation, treatment of heart failure and invasive
      hemodynamic support are cornerstones of the treatment. We present an algorithm
      which may help to organize an optimized treatment for each ES patient,
      implementing invasive treatment options like coronary angioplasty, catheter
      ablation and invasive circulatory support. Further studies are necessary to
      evaluate medium term outcome of such a structured therapy.

PMID- 24898993
TI  - Miracle baby: managing extremely preterm birth in rural Uganda.
AB  - Preterm birth is an important cause of neonatal morbidity and mortality globally.
      Uganda has one of the highest rates of preterm birth in East Africa but few
      resources to care for these infants. This case highlights the clinical course of
      an extremely premature infant born at 26 weeks gestation to a nulliparous 24-year
      old woman. Her mother was involved in her care and taught the principles of
      kangaroo mother care. After initial problems establishing feeds she progressed
      well and was discharged in the fifth week of life. The case describes some of the
      low technology conservative and medical measures which can be used to care for
      neonates, such as antenatal steroids and kangaroo care. The use of antibiotics
      and aminophylline are also discussed. The approach to the common challenges faced
      by premature infants such as respiratory disease, sepsis and necrotising
      enterocolitis in a resource-poor environment are discussed. 

PMID- 24898994
TI  - Primary uterine osteosarcoma presenting synchronously with bilateral breast
      carcinomas.
AB  - Primary uterine sarcomas are infrequent neoplasms and most commonly
      leiomyosarcomas or endometrial stromal sarcomas. We report a rare case of primary
      uterine osteosarcoma discovered in a woman in her 60s following staging CT
      imaging for bilateral breast carcinomas. Examination of the subsequent
      hysterectomy specimen showed a tumour composed of malignant spindle cells and
      osteoclast-like giant cells associated with osteoid and neoplastic bone, in
      keeping with primary uterine osteosarcoma. Distinction of osteosarcoma from the
      more common carcinosarcoma is important due to the worse prognosis impacting on
      treatment decisions. In addition, synchronous presentation of this unusual tumour
      with bilateral breast carcinomas raises the possibility of a mutual genetic
      pathogenesis. 

PMID- 24898995
TI  - Chiari type 1 malformation in a pseudotumour cerebri patient: is it an acquired
      or congenital Chiari malformation?
AB  - Chiari malformation type 1 (CM1) is a developmental abnormality of the cerebellar
      tonsils. Patients with CM1 commonly present with headache. Papilloedema is rarely
      seen in CM1. However, a 52-year-old woman presented to the hospital with a
      headache and her ophthalmological examination revealed bilateral papilloedema.
      Her cranial MRI was compatible with borderline CM1. Bilateral papilloedema and
      headache suggested idiopathic intracranial hypertension (IIH) as the preliminary
      diagnosis. IIH is a rare case in CM1. This article argues about this association
      and discusses as to whether it is an acquired or congenital Chiari malformation. 

PMID- 24898996
TI  - Cognitive behavioural therapy for depression in multiple endocrine neoplasia type
      IIB: a 1-year follow-up.
AB  - This case report describes a 24-year-old man diagnosed with multiple endocrine
      neoplasia type IIB and major depression. Because cognitive behavioural therapy
      (CBT) has proven effective in the treatment of major depression in the general
      population and patients with cancer, we decided to adapt and use this therapy and
      evaluate its impact on major depression and the patient's quality of life. The
      therapy was conducted individually in 15 sessions that were given over a span of
      25 weeks. The data show that therapy was a useful treatment that reduced
      depression according to the Diagnostic and Statistical Manual of Mental Disorders
      (DSM)-IV criteria and self-report instruments. CBT also helped improve the
      patient's quality of life, and it was considered to be an acceptable intervention
      for the patient, with ongoing positive results 1 year after the last
      psychotherapy session. CBT is a potential option for treating depression in this
      population but further research is needed.

PMID- 24898997
TI  - Spontaneous haemorrhage in a healthy newborn.

PMID- 24898998
TI  - Adult-onset Still's disease presenting as myopericarditis.
AB  - A 24-year-old man presented to the emergency department with fever, maculopapular
      rash, myalgia and polyarthralgia, thoracic pain and dry cough, which had been
      present for 24 h. At the time of observation he had high fever (39 degrees C),
      maculopapular rash on the torso, arms and legs proximally, axillary adenopathies
      and pharyngitis. Laboratorial data showed elevated inflammation markers
      (leukocytosis, C reactive protein of 44 mg/dL, erythrocyte sedimentation rate of
      120 mm), elevated transaminases, lactate dehydrogenase, ferritin levels (>2000
      ng/mL) and rising troponin. ECG had sinus rhythm and ST elevation in leads V1-V5.
      Thoracic radiography revealed bilateral interstitial infiltrate confirmed by CT
      scan. Echocardiographic findings included diffuse hypokinesia of the left
      ventricle and impaired systolic function. After the investigation of an
      infectious or autoimmune aetiology was negative, the diagnosis of adult-onset
      Still's disease was considered. The patient was put on a 60 mg/day prednisolone
      regimen with remission of symptoms and normalisation of systolic function and
      ECG.

PMID- 24898999
TI  - Acute psychosis with attention-deficit/hyperactivity disorder and oppositional
      defiant disorder comorbidities.
AB  - This is a case of an 18-year-old boy who presented with his mother in the
      emergency room with a 1-week history of paranoia and bizarre behaviour. His
      comorbidities included attention-deficit/hyperactivity disorder, oppositional
      defiant disorder and mild intellectual delay. At the emergency room he was
      incoherent, agitated and uncooperative. He was admitted to the psychiatric
      inpatient unit and treated with low-dose risperidone. The patient's symptoms
      improved markedly over a few days, although he remained restless and had episodes
      of agitation. Nursing staff was concerned about his behaviour and found him
      difficult to manage. However, after speaking to the patient's family, this was
      felt to be his baseline. After 11 days the patient was discharged home in stable
      state. 

PMID- 24899000
TI  - Cluster-like headache responsive to phlebotomy.
AB  - We report the first case of cluster-like headache secondary to polycythaemia vera
      (PV) that responded to phlebotomy as part of PV treatment. 

PMID- 24899001
TI  - Metastatic human epidermal growth factor 2 (HER2/neu) amplified breast cancer
      with acute fulminant hepatitis responding to trastuzumab, pertuzumab and
      carboplatin.
AB  - A 30-year-old woman presented to an outside hospital with pain in the right upper
      abdomen. Imaging revealed over 100 liver lesions, the largest measuring 74 mm*71
      mm, and multiple lytic bone lesions. An outpatient liver biopsy showed a poorly
      differentiated adenocarcinoma favouring a breast primary. The tumour was
      oestrogen and progesterone receptor negative, but human epidermal growth factor 2
      (HER2/neu) amplified. In her second clinic visit she had decompensated liver
      failure manifested by new-onset ascites and jaundice. Initially, the chemotherapy
      plan was for docetaxel, pertuzumab and trastuzumab, but given her severe liver
      dysfunction we used a combination of carboplatin, pertuzumab and trastuzumab as
      an inpatient. She was hospitalised for 14 days and eventually discharged with a
      marked improvement of her symptoms and liver tests. She subsequently completed
      five outpatient chemotherapy cycles. We showed that carboplatin is a possible
      alternative to docetaxel when severe liver dysfunction precludes docetaxel's use
      in combination with pertuzumab and trastuzumab. 

PMID- 24899003
TI  - Self-mutilation of teeth due to peer pressure: an aspect of child psychology.

PMID- 24899002
TI  - An important case of misdiagnosis: keloid scar or high-grade soft-tissue sarcoma?

PMID- 24899004
TI  - Abdominal wall disruption with evisceration after blunt trauma.
AB  - Abdominal evisceration after blunt trauma is rare. We report a case in a 65-year
      old man who was crushed by a lorry. Management of this uncommon condition is
      reviewed. 

PMID- 24899005
TI  - Acute hepatitis E complicated by acute pancreatitis and multiorgan dysfunction.
AB  - We report this rare case of a 27-year-old man who presented with acute hepatitis
      E and went on to develop acute epigastric pain. He was diagnosed to have acute
      severe pancreatitis with shock and acute renal failure due to hepatitis E. Such a
      phenomenon has rarely been reported in the literature, with patients following a
      benign course and complete recovery after conservative management and analgesia.
      Awareness of this potentially life-threatening complication, especially in young
      men from endemic areas with acute hepatitis E presenting with abdomen pain has
      been highlighted. 

PMID- 24899007
TI  - Cutis marmorata marbling in an individual with decompression illness following
      repetitive SCUBA diving.

PMID- 24899006
TI  - Autism: a rare presentation of Bardet-Biedl syndrome.
AB  - Although mental retardation is generally associated with Bardet-Biedl (BBS)
      syndrome, a rare autosomal recessive disorder with multisystem involvement,
      autism is an unusual comorbidity. An 8-year-old boy presented to our psychiatry
      department with poor social skills and night blindness. On further assessment
      autism, mild mental retardation, retinitis pigmentosa, polydactyly and
      syndactyly, obesity, micropenis, maldescended testis, hypodontia and high-arched
      palate were noted and subsequently a diagnosis of BBS was made. To the best of
      our knowledge, this is the first reported case of BBS with autism from eastern
      India; it also emphasises the importance of thorough physical examination even in
      a patient presenting with pure psychiatric symptoms. 

PMID- 24899009
TI  - Evaluation of mild encephalitis/encephalopathy with a reversible splenial lesion
      (MERS) by diffusion-weighted and diffusion tensor imaging.
AB  - Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a
      clinicoradiological entity with varied aetiologies and having a typical course of
      evolution. We present a case of MERS evaluated with diffusion-weighted and
      diffusion tensor imaging along with various conventional sequences of MRI. At the
      time of presentation, the lesions in the splenium of corpus callosum and
      bilateral cerebral white matter showed diffusion restriction with reduced
      apparent diffusion coefficient and no reduction in fractional anisotropy (FA)
      values on diffusion tensor imaging; on follow-up diffusion restriction completely
      resolved with normalisation of the apparent diffusion coefficient. The normal to
      slightly increased FA values in the lesions may indicate that MERS is a non
      degenerative disorder. 

PMID- 24899008
TI  - Acute peripheral polyneuropathy with multiorgan failure: a diagnostic dilemma.
AB  - We describe the case of a young man who presented with abdominal pain, vomiting
      and acute symmetric peripheral polyneuropathy. He was noted to have high anion
      gap metabolic acidosis with high lactate levels and persistently high arterial
      and venous pO2 values. The cerebrospinal fluid was acellular with a high protein
      and the nerve conduction study was consistent with axonal sensorimotor
      neuropathy. His clinical condition deteriorated rapidly despite full supportive
      care and he subsequently died of multiorgan failure. An extensive workup for
      various infectious, autoimmune and other possible aetiologies was carried out to
      identify the underlying cause for his fulminant illness. All diagnostic workup
      was non-conclusive except for a significantly elevated serum aluminium level. We
      have discussed the possibility of aluminium phosphide poisoning in view of the
      clinical presentation. 

PMID- 24899010
TI  - Kikuchi-Fujimoto disease and acute appendicitis.
AB  - A 29-year-old Japanese man developed fever, nausea, vomiting, diarrhoea, right
      lower quadrant abdominal pain and rebound tenderness. With the clinical suspicion
      of appendicitis, an abdominal CT scan was performed, which revealed mesenteric
      lymphadenitis. The patient was hospitalised and treated with antibiotics, but was
      ultimately found to have Kikuchi-Fujimoto disease (KFD). This diagnosis was
      facilitated by the use of positron emission tomography scan that identified an
      accessible inguinal lymph node for biopsy and histopathological evaluation.
      Invasive abdominal surgery was thereby averted and the patient made a complete
      recovery on subsequent follow-up. Review of the published literature reveals that
      pseudoappendicitis due to KFD is a rare occurrence that has generally required
      abdominal surgery to establish the diagnosis, thus supporting the potential value
      of the approach taken here. 

PMID- 24899011
TI  - Haemolytic anaemia--PNH type II cells presenting a diagnostic dilemma.
AB  - A 28-year-old man presented with a history of intermittent haematuria over the
      past 10 years usually following fever episodes and requiring blood transfusions
      during the episodes. History of any thrombotic complications, chest pain or
      erectile dysfunction was not forthcoming. Examination revealed severe pallor with
      mild icterus and mild splenomegaly. His blood picture showed pancytopenia with
      elevated reticulocytes and indirect hyperbilirubinaemia. Indirect Coombs test was
      positive but direct was negative, serum lactate dehydrogenase was elevated and
      agglutinins were found to be of IgG type. Bone marrow showed a hypercellular
      marrow with myeloid and megakaryocytes suppressed. Donath-Landsteiner antibodies
      were found to be negative ruling out paroxysmal cold haemoglobinuria. Flow
      cytometry was performed with a suspicion of paroxysmal nocturnal haemoglobinuria
      (PNH) and was shown to be partially negative for CD59 but positive for CD55, a
      pattern consistent with type II PNH.

PMID- 24899012
TI  - Fishbone perforation of the gastrointestinal tract in patients with acute
      abdominal pain: diagnosis using plain film radiography.

PMID- 24899014
TI  - Opioid-induced hyperalgesia: when pain killers make pain worse.
AB  - A 44-year-old woman had a temporal glioma and was admitted to the hospice with
      pain that was not controlled despite escalating opioids. Her pain levels rose
      after every dose increase resulting now in continuous pain, making her very low
      in mood. Her short-term memory had also declined in a stepwise fashion with each
      increase in opioids. Additionally, her poor health had had a detrimental effect
      on family life. Physical examination was difficult due to allodynia but no major
      abnormality was found. The team suspected opioid-induced hyperalgesia and decided
      to cut the patient's opioids by one-third initially. This immediately improved
      the overall pain. The opioids continued to be decreased incrementally every 1-2
      days until the pain had disappeared completely. She was stabilised on a dose
      almost one-seventh of her original regime. Mood and memory also improved as
      opioids decreased and she was discharged home after 8 days.

PMID- 24899013
TI  - Unreported neurological complications of Gemella bergeriae infective
      endocarditis.
AB  - We report the first case of native aortic and mitral valve endocarditis due to
      Gemella bergeriae from the Middle East in a young patient with rheumatic heart
      disease. Our case illustrates a fulminant course of infection with G. bergeriae
      endocarditis that was complicated by embolic stroke, as well as intracerebral and
      subarachnoid haemorrhage secondary to rupture of a mycotic aneurysm in the right
      middle cerebral artery. This case highlights the dire, unreported neurological
      complications of infective endocarditis due to a rare causative organism-G.
      bergeriae. 

PMID- 24899015
TI  - Verrucous haemangioma: a diagnosis to consider.

PMID- 24899016
TI  - Management of pregnancy in woman with suspected malignant deep infiltrating
      endometriosis fistulised to the uterine cervix.
AB  - Deep infiltrating endometriosis (DIE) is a well-known cause of pelvic pain and
      infertility. Malignant transformation of DIE is rare but can be suggested by MRI.
      We report a case of a spontaneous pregnancy in a woman with suspicion of
      malignant transformation of DIE with fistulisation to the posterior uterine
      isthmus through to the cervical canal. The pregnancy was closely monitored and an
      uneventful caesarian section was performed at 34 weeks of gestation. This case
      raises the issue of the relevance of imaging techniques and management of
      pregnancy. 

PMID- 24899017
TI  - Multidermatomal herpes zoster.

PMID- 24899018
TI  - Diagnostic accuracy of a molecular drug susceptibility testing method for the
      antituberculosis drug ethambutol: a systematic review and meta-analysis.
AB  - Ethambutol (EMB) is a first-line antituberculosis drug; however, drug resistance
      to EMB has been increasing. Molecular drug susceptibility testing (DST), based on
      the embB gene, has recently been used for rapid identification of EMB resistance.
      The aim of this meta-analysis was to establish the accuracy of molecular assay
      for detecting drug resistance to EMB. PubMed, Embase, and Web of Science were
      searched according to a written protocol and explicit study selection criteria.
      Measures of diagnostic accuracy were pooled using a random effects model. A total
      of 34 studies were included in the meta-analysis. The respective pooled
      sensitivities and specificities were 0.57 and 0.93 for PCR-DNA sequencing that
      targeted the embB 306 codon, 0.76 and 0.89 for PCR-DNA sequencing that targeted
      the embB 306, 406, and 497 codons, 0.64 and 0.70 for detecting Mycobacterium
      tuberculosis isolates, 0.55 and 0.78 for detecting M. tuberculosis sputum
      specimens using the GenoType MTBDRsl test, 0.57 and 0.87 for pyrosequencing, and
      0.35 and 0.98 for PCR-restriction fragment length polymorphism. The respective
      pooled sensitivities and specificities were 0.55 and 0.92 when using a lower EMB
      concentration as the reference standard, 0.67 and 0.73 when using a higher EMB
      concentration as the reference standard, and 0.60 and 1.0 when using multiple
      reference standards. PCR-DNA sequencing using multiple sites of the embB gene as
      detection targets, including embB 306, 406, and 497, can be a rapid method for
      preliminarily screening for EMB resistance, but it does not fully replace
      phenotypic DST. Of the reference DST methods examined, the agreement rates were
      the best using MGIT 960 for molecular DST and using the proportion method on
      Middlebrook 7H10 media. 

PMID- 24899020
TI  - Cervical and vaginal flora specimens are highly concordant with respect to
      bacterial vaginosis-associated organisms and commensal Lactobacillus species in
      women of reproductive age.
AB  - Matched vaginal and cervical specimens from 96 subjects were analyzed by
      quantitative PCR for the presence and concentration of bacterial vaginosis
      associated microbes and commensal Lactobacillus spp. Detection of these microbes
      was 92% concordant, indicating that microbial floras at these body sites are
      generally similar. 

PMID- 24899019
TI  - Multilocus sequence typing scheme versus pulsed-field gel electrophoresis for
      typing Mycobacterium abscessus isolates.
AB  - Outbreaks of infections by rapidly growing mycobacteria following invasive
      procedures, such as ophthalmological, laparoscopic, arthroscopic, plastic, and
      cardiac surgeries, mesotherapy, and vaccination, have been detected in Brazil
      since 1998. Members of the Mycobacterium chelonae-Mycobacterium abscessus group
      have caused most of these outbreaks. As part of an epidemiological investigation,
      the isolates were typed by pulsed-field gel electrophoresis (PFGE). In this
      project, we performed a large-scale comparison of PFGE profiles with the results
      of a recently developed multilocus sequence typing (MLST) scheme for M.
      abscessus. Ninety-three isolates were analyzed, with 40 M. abscessus subsp.
      abscessus isolates, 47 M. abscessus subsp. bolletii isolates, and six isolates
      with no assigned subspecies. Forty-five isolates were obtained during five
      outbreaks, and 48 were sporadic isolates that were not associated with outbreaks.
      For MLST, seven housekeeping genes (argH, cya, glpK, gnd, murC, pta, and purH)
      were sequenced, and each isolate was assigned a sequence type (ST) from the
      combination of obtained alleles. The PFGE patterns of DraI-digested DNA were
      compared with the MLST results. All isolates were analyzable by both methods.
      Isolates from monoclonal outbreaks showed unique STs and indistinguishable or
      very similar PFGE patterns. Thirty-three STs and 49 unique PFGE patterns were
      identified among the 93 isolates. The Simpson's index of diversity values for
      MLST and PFGE were 0.69 and 0.93, respectively, for M. abscessus subsp. abscessus
      and 0.96 and 0.97, respectively, for M. abscessus subsp. bolletii. In conclusion,
      the MLST scheme showed 100% typeability and grouped monoclonal outbreak isolates
      in agreement with PFGE, but it was less discriminative than PFGE for M.
      abscessus. 

PMID- 24899021
TI  - GyrB polymorphisms accurately assign invasive viridans group streptococcal
      species.
AB  - Viridans group streptococci (VGS) are a heterogeneous group of medically
      important bacteria that cannot be accurately assigned to a particular species
      using conventional phenotypic methods. Although multilocus sequence analysis
      (MLSA) is considered the gold standard for VGS species-level identification, MLSA
      is not yet feasible in the clinical setting. Conversely, molecular methods, such
      as sodA and 16S rRNA gene sequencing, are clinically practical but not
      sufficiently accurate for VGS species-level identification. Here, we present data
      regarding the use of an ~ 400-nucleotide internal fragment of the gene encoding
      DNA gyrase subunit B (GyrB) for VGS species-level identification. MLSA, internal
      gyrB, sodA, full-length, and 5' 16S gene sequences were used to characterize 102
      unique VGS blood isolates collected from 2011 to 2012. When using the MLSA
      species assignment as a reference, full-length and 5' partial 16S gene and sodA
      sequence analyses failed to correctly assign all strains to a species. Precise
      species determination was particularly problematic for Streptococcus mitis and
      Streptococcus oralis isolates. However, the internal gyrB fragment allowed for
      accurate species designations for all 102 strains. We validated these findings
      using 54 VGS strains for which MLSA, 16S gene, sodA, and gyrB data are available
      at the NCBI, showing that gyrB is superior to 16S gene and sodA sequence analyses
      for VGS species identification. We also observed that specific polymorphisms in
      the 133-amino acid sequence of the internal GyrB fragment can be used to identify
      invasive VGS species. Thus, the GyrB amino acid sequence may offer a more
      practical and accurate method for classifying invasive VGS strains to the species
      level.

PMID- 24899023
TI  - Asymptomatic "Candidatus Neoehrlichia mikurensis" infections in immunocompetent
      humans.
AB  - In Europe, human infections with "Candidatus Neoehrlichia mikurensis" have mainly
      been restricted to immunocompromised patients. We report here the first cases of
      asymptomatic "Ca. Neoehrlichia mikurensis" infection in immunocompetent humans
      (5/316 [1.6%] were infected). Due to the potential threats of infections with
      "Ca. Neoehrlichia mikurensis" in healthy persons to the safety of the blood
      supply, further study of this phenomenon is required. 

PMID- 24899022
TI  - Development of a rapid microarray-based DNA subtyping assay for the alleles of
      Shiga toxins 1 and 2 of Escherichia coli.
AB  - In this study, we developed a new rapid, economic, and automated microarray-based
      genotyping test for the standardized subtyping of Shiga toxins 1 and 2 of
      Escherichia coli. The microarrays from Alere Technologies can be used in two
      different formats, the ArrayTube and the ArrayStrip (which enables high
      throughput testing in a 96-well format). One microarray chip harbors all the gene
      sequences necessary to distinguish between all Stx subtypes, facilitating the
      identification of single and multiple subtypes within a single isolate in one
      experiment. Specific software was developed to automatically analyze all data
      obtained from the microarray. The assay was validated with 21 Shiga toxin
      producing E. coli (STEC) reference strains that were previously tested by the
      complete set of conventional subtyping PCRs. The microarray results showed 100%
      concordance with the PCR results. Essentially identical results were detected
      when the standard DNA extraction method was replaced by a time-saving heat lysis
      protocol. For further validation of the microarray, we identified the Stx
      subtypes or combinations of the subtypes in 446 STEC field isolates of human and
      animal origin. In summary, this oligonucleotide array represents an excellent
      diagnostic tool that provides some advantages over standard PCR-based subtyping.
      The number of the spotted probes on the microarrays can be increased by
      additional probes, such as for novel alleles, species markers, or resistance
      genes, should the need arise. 

PMID- 24899024
TI  - Sensitivity of real-time PCR performed on dried sera spotted on filter paper for
      diagnosis of leptospirosis.
AB  - In remote countries, leptospirosis confirmation is difficult because it requires
      the shipment of frozen samples to reference laboratories. The sensitivity of
      leptospirosis real-time PCR performed on filter paper-dried serum samples stored
      at ambient temperature was evaluated at 2 * 10(2) equivalent leptospires/ml
      (eqLeptospires/ml). This easy alternative procedure can be used to enhance the
      surveillance of leptospirosis. 

PMID- 24899026
TI  - Performance of the Verigene Gram-negative blood culture assay for rapid detection
      of bacteria and resistance determinants.
AB  - Nonduplicate blood cultures that were positive for Gram-negative bacilli (n =
      125) were tested by the Verigene Gram-negative blood culture (BC-GN) assay; 117
      (90.7%) isolates were members of the panel. For identification and resistance
      markers, the agreements with routine methods were 97.4% (114/117) and 92.3%
      (12/13). The BC-GN assay is a rapid and accurate tool for the detection of
      pathogens from blood cultures and could be integrated alongside conventional
      systems to enable faster patient management, but the clinical benefits should be
      further evaluated. 

PMID- 24899025
TI  - Analytic and clinical performance of cobas HPV testing in anal specimens from HIV
      positive men who have sex with men.
AB  - Anal human papillomavirus (HPV) infections are common, and the incidence of anal
      cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the
      performance of HPV assays in anal samples, we compared the cobas HPV test (cobas)
      to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected
      MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We
      calculated agreement between the HPV assays and the clinical performance of HPV
      testing and HPV genotyping alone and in combination with anal cytology. We
      observed high agreement between cobas and LA, with cobas more likely than LA to
      show positive results for HPV16, HPV18, and other carcinogenic types. Specimens
      testing positive in cobas but not in LA were more likely to be positive for other
      markers of HPV-related disease compared to those testing negative in both assays,
      suggesting that at least some of these were true positives for HPV. cobas and LA
      showed high sensitivities but low specificities for the detection of anal
      intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity
      and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for
      LA). A combination of anal cytology and HPV genotyping provided the highest
      accuracy for detecting anal precancer. A higher HPV load was associated with a
      higher risk of AIN2/3 with HPV16 (P(trend) < 0.001), HPV18 (P(trend) = 0.07), and
      other carcinogenic types (P(trend) < 0.001). We demonstrate that cobas can be
      used for HPV detection in anal cytology specimens. Additional tests are necessary
      to identify men at the highest risk of anal cancer among those infected with high
      risk HPV.

PMID- 24899028
TI  - Probiotic-associated aspiration pneumonia due to Lactobacillus rhamnosus.
AB  - Lactobacilli are low-virulence, commensal organisms of the gastrointestinal and
      genitourinary tracts and are commonly used as "probiotic supplements." Herein, we
      describe an episode of respiratory syncytial virus (RSV) bronchiolitis with
      bacterial superinfection secondary to administration of Lactobacillus rhamnosus
      in an 11-month-old female with trisomy 21. 

PMID- 24899027
TI  - Time to positivity and detection of growth in anaerobic blood culture vials
      predict the presence of Candida glabrata in candidemia: a two-center European
      cohort study.
AB  - This study shows the accuracy of exclusive or earlier growth in anaerobic vials
      to predict Candida glabrata in a large series of candidemic patients from two
      European hospitals using the Bactec 9240 system. Alternatively, C. glabrata can
      be predicted by a time to positivity cutoff value, which should be determined for
      each setting. 

PMID- 24899029
TI  - Detection of hepatitis B virus genotypic resistance mutations by coamplification
      at lower denaturation temperature-PCR coupled with sanger sequencing.
AB  - Mutations in the reverse transcriptase (rt) region of the DNA polymerase gene are
      the primary cause of hepatitis B virus (HBV) drug resistance. In this study, we
      established a novel method that couples coamplification at lower denaturation
      temperature (COLD)-PCR and Sanger sequencing, and we applied it to the detection
      of known and unknown HBV mutations. Primers were designed based on the common
      mutations in the HBV rt sequence at positions 180 to 215. The critical
      denaturation temperature (Tc) was established as a denaturing temperature for
      both fast and full COLD-PCR procedures. For single mutations, when a melting
      temperature (Tm)-reducing mutation occurred (e.g., C-G -> T-A), the sensitivities
      of fast and full COLD-PCR for mutant detection were 1% and 2%, respectively; when
      the mutation caused no change in Tm (e.g., C-G -> G-C) or raised Tm (e.g., T-A ->
      C-G), only full COLD-PCR improved the sensitivity for mutant detection (2%). For
      combination mutations, the sensitivities of both full and fast COLD-PCR were
      increased to 0.5%. The limits of detection for fast and full COLD-PCR were 50
      IU/ml and 100 IU/ml, respectively. In 30 chronic hepatitis B (CHB) cases, no
      mutations were detected by conventional PCR, whereas 18 mutations were
      successfully detected by COLD-PCR, including low-prevalence mutations (<10%), as
      confirmed by ultradeep pyrosequencing. In conclusion, COLD-PCR provides a highly
      sensitive, simple, inexpensive, and practical tool for significantly improving
      amplification efficacy and detecting low-level mutations in clinical CHB cases.

PMID- 24899030
TI  - Competency assessment of microbiology medical laboratory technologists in
      Ontario, Canada.
AB  - Accreditation in Ontario, Canada, requires that licensed clinical laboratories
      participate in external quality assessment (also known as proficiency testing)
      and perform competency evaluation of their staff. To assess the extent of ongoing
      competency assessment practices, the Quality Management Program--Laboratory
      Services (QMP-LS) Microbiology Committee surveyed all 112 licensed Ontario
      microbiology laboratories. The questionnaire consisted of a total of 21 questions
      that included yes/no, multiple-choice, and short-answer formats. Participants
      were asked to provide information about existing programs, the frequency of
      testing, what areas are evaluated, and how results are communicated to the staff.
      Of the 111 responding laboratories, 6 indicated they did not have a formal
      evaluation program since they perform only limited bacteriology testing. Of the
      remaining 105 respondents, 87% perform evaluations at least annually or every 2
      years, and 61% include any test or task performed, whereas 16% and 10% focus only
      on problem areas and high-volume complex tasks, respectively. The most common
      methods of evaluation were review of external quality assessment (EQA)
      challenges, direct observation, and worksheet review. With the exception of one
      participant, all communicate results to staff, and most take remedial action to
      correct the deficiencies. Although most accredited laboratories have a program to
      assess the ongoing competency of their staff, the methods used are not
      standardized or consistently applied, indicating that there is room for
      improvement. The survey successfully highlighted potential areas for improvement
      and allowed the QMP-LS Microbiology Committee to provide guidance to Ontario
      laboratories for establishing or improving existing microbiology-specific
      competency assessment programs.

PMID- 24899031
TI  - New PCR-based open reading frame typing method for easy, rapid, and reliable
      identification of Acinetobacter baumannii international epidemic clones without
      performing multilocus sequence typing.
AB  - Antimicrobial resistance issues have become a global health concern. The rapid
      identification of multidrug-resistant microbes, which depends on microbial
      genomic information, is essential for overcoming growing antimicrobial resistance
      challenges. However, genotyping methods, such as multilocus sequence typing
      (MLST), for identifying international epidemic clones of Acinetobacter baumannii
      are not easily performed as routine tests in ordinary clinical laboratories. In
      this study, we aimed to develop a novel genotyping method that can be performed
      in ordinary microbiology laboratories. Several open reading frames (ORFs)
      specific to certain bacterial genetic lineages or species, together with their
      unique distribution patterns on the chromosomes showing a good correlation with
      the results of MLST, were selected in A. baumannii and other Acinetobacter spp.
      by comparing their genomic data. The distribution patterns of the ORFs were
      visualized by agarose gel electrophoresis after multiplex PCR amplification and
      digitized. A. baumannii sequence types (STs) corresponding to international
      clones I and II were successfully discriminated from other STs and Acinetobacter
      species by detecting the distribution patterns of their ORFs using the multiplex
      PCR developed here. Since bacterial STs can be easily expressed as digitized
      numeric data with plus (+) expressed as 1 and minus (-) expressed as 0, the
      results of the method can be easily compared with those obtained by different
      tests or laboratories. This PCR-based ORF typing (POT) method can easily and
      rapidly identify international epidemic clones of A. baumannii and differentiate
      this microbe from other Acinetobacter spp. Since this POT method is easy enough
      to be performed even in ordinary clinical laboratories, it would also contribute
      to daily infection control measures and surveillance. 

PMID- 24899032
TI  - Site-specific clinical evaluation of the Luminex xTAG gastrointestinal pathogen
      panel for detection of infectious gastroenteritis in fecal specimens.
AB  - We evaluate the clinical performance of the Luminex xTAG gastrointestinal (GI)
      pathogen in vitro diagnostic (IVD) assay in a comparison between clinical and
      public health laboratories. The site reproducibility study showed 98.7%
      sensitivity with high positive and negative agreement values (96.2% and 99.8%,
      respectively), while assay performance against confirmatory methods resulted in
      96.4% sensitivity with similar positive and negative agreement values (90.1% and
      99.5%, respectively). High-throughput detection of multiple GI pathogens improved
      turnaround time, consolidated laboratory workflow, and simplified stool culture
      practices, thus reducing the overall cost and number of specimens processed. 

PMID- 24899033
TI  - Molecular characterization of methicillin-resistant Staphylococcus aureus
      clinical isolates obtained from the Rikers Island Jail System from 2009 to 2013.
AB  - Inmates of Rikers Island jail potentially introduce Staphylococcus aureus into
      New York State prisons upon transfer. In this study, methicillin-resistant
      Staphylococcus aureus isolates (n = 452), collected from infected inmates (2009
      to 2013), were characterized. spa type t008 was the predominant clone identified,
      accounting for 82.3% of the isolates, with no evidence of mupirocin or
      chlorhexidine resistance. 

PMID- 24899034
TI  - Zoonotic anatrichosomiasis in a mother and daughter.
AB  - Zoonotic anatrichosomiasis in a mother and daughter is reported. Both presented
      with a 10-week history of multiple painful oral ulcers. Biopsy specimens revealed
      the presence of small, coiled trichuroid nematodes with distinctive morphological
      features, including stichocytes and paired bacillary bands. This represents an
      unusual infection by a zoonotic Anatrichosoma species. 

PMID- 24899035
TI  - Unexpected Blastomyces dermatitidis etiology of fungal sinusitis and erosive
      palatal infection in a diabetic patient.
AB  - We present what is believed to be the initial report of hard-palate infection
      caused by Blastomyces dermatitidis. The organism was cultivated from biopsy
      material obtained from a diabetic patient presenting with complaints of headache
      and malaise. Radiologic findings revealed a malignant-appearing soft-tissue mass
      with paranasal sinus base destruction. 

PMID- 24899037
TI  - Prevalence of recovirus-neutralizing antibodies in human serum samples.
AB  - To investigate recovirus infections and their association with zoonosis, the
      prevalence of the virus-neutralizing antibody against three recovirus serotypes
      was tested in the general population and in zookeepers. Neutralizing antibodies
      were detected in a significantly higher number of zookeepers than in the general
      population but with significantly lower titers than in macaques. 

PMID- 24899036
TI  - Evaluation of a new protocol for retrospective diagnosis of congenital
      toxoplasmosis by use of Guthrie cards.
AB  - The aim of this study was to assess the diagnostic value of IgM Western blotting
      (WB), IgA enzyme immunoassay (EIA), and DNA amplification by real-time PCR on
      Guthrie cards to retrospectively establish the diagnosis of congenital
      toxoplasmosis (CT). To this purpose, Guthrie cards were collected from 18 infants
      born to mothers with primary Toxoplasma gondii infection during pregnancy.
      Moreover, the analytical sensitivity of T. gondii PCR was assessed by testing
      mock dried blood specimens set up with several known DNA dilutions. IgM WB was
      demonstrated to be the most sensitive method. When the results of T. gondii DNA
      detection and specific IgM recovery were combined, retrospective CT diagnosis by
      using Guthrie cards was established in 3 out of 6 infected infants (sensitivity,
      50%; 95% confidence interval, 26.8% to 73.2%). No positive PCR or serologic
      results were found in the group of 12 uninfected infants, demonstrating the
      excellent specificity of the three methods (95% confidence interval, 78.1% to
      99.5%). The findings of the present study suggest that, in cases of missed
      diagnosis of CT at birth, analysis of Guthrie cards for children with compatible
      clinical findings after the perinatal period, in particular the combination of
      recovery of specific IgM antibodies and T. gondii DNA amplification, could be
      helpful. Nevertheless, since suboptimal conditions of storage of dried blood
      specimens can seriously affect sensitivity, negative results cannot rule out CT
      diagnosis. In contrast, because of the excellent specificity shown by IgM
      serologic testing and T. gondii DNA amplification on Guthrie cards, positive
      results obtained by either of the two methods should be considered diagnostic. 

PMID- 24899038
TI  - Evaluation of the Bruker Biotyper matrix-assisted laser desorption ionization
      time of flight mass spectrometry system for identification of blood isolates of
      Acinetobacter species.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) (Bruker Biotyper) was able to accurately identify 98.6% (142/144)
      of Acinetobacter baumannii isolates, 72.4% (63/87) of A. nosocomialis isolates,
      and 97.6% (41/42) of A. pittii isolates. All Acinetobacter junii, A. ursingii, A.
      johnsonii, and A. radioresistens isolates (n = 28) could also be identified
      correctly by Bruker Biotyper. 

PMID- 24899040
TI  - New clustered regularly interspaced short palindromic repeat locus spacer pair
      typing method based on the newly incorporated spacer for Salmonella enterica.
AB  - A clustered regularly interspaced short palindromic repeat (CRISPR) typing method
      has recently been developed and used for typing and subtyping of Salmonella spp.,
      but it is complicated and labor intensive because it has to analyze all spacers
      in two CRISPR loci. Here, we developed a more convenient and efficient method,
      namely, CRISPR locus spacer pair typing (CLSPT), which only needs to analyze the
      two newly incorporated spacers adjoining the leader array in the two CRISPR loci.
      We analyzed a CRISPR array of 82 strains belonging to 21 Salmonella serovars
      isolated from humans in different areas of China by using this new method. We
      also retrieved the newly incorporated spacers in each CRISPR locus of 537
      Salmonella isolates which have definite serotypes in the Pasteur Institute's
      CRISPR Database to evaluate this method. Our findings showed that this new CLSPT
      method presents a high level of consistency (kappa = 0.9872, Matthew's
      correlation coefficient = 0.9712) with the results of traditional serotyping, and
      thus, it can also be used to predict serotypes of Salmonella spp. Moreover, this
      new method has a considerable discriminatory power (discriminatory index [DI] =
      0.8145), comparable to those of multilocus sequence typing (DI = 0.8088) and
      conventional CRISPR typing (DI = 0.8684). Because CLSPT only costs about $5 to
      $10 per isolate, it is a much cheaper and more attractive method for subtyping of
      Salmonella isolates. In conclusion, this new method will provide considerable
      advantages over other molecular subtyping methods, and it may become a valuable
      epidemiologic tool for the surveillance of Salmonella infections. 

PMID- 24899039
TI  - Mucosal disease-like syndrome in a calf persistently infected by Hobi-like
      pestivirus.
AB  - A calf persistently infected with Hobi-like pestivirus displayed severe clinical
      signs and subsequently died. Gross lesions and histopathological changes were
      suggestive of hemorrhagic and necrotic inflammation involving several tissues. A
      Hobi-like pestivirus pair was isolated from the dead calf, i.e., cytopathogenic
      (CP) and noncytopathogenic (NCP) strains strictly related to each other and to
      Italian prototype isolates at the genetic level. Two biotype-specific real-time
      reverse transcription-PCR assays determined the time of the emergence of the CP
      virus as 1 month before the calf's death. This highest RNA titers were reached in
      lymphoid and nervous system tissues, whereas only traces of CP viral RNA were
      found in blood. In contrast, great NCP virus loads were present in all tissues
      and biological fluids. The present report provides new insights into the
      pathogenesis and molecular mechanisms of this emerging group of pestiviruses. 

PMID- 24899041
TI  - Characteristics of acute nongonococcal urethritis in men differ by sexual
      preference.
AB  - Nongonococcal urethritis (NGU) is a common clinical syndrome, but no etiological
      agent is identified in a significant proportion of cases. Whether the spectrum of
      pathogens differs between heterosexual men (MSW) and men who have sex with men
      (MSM) is largely unstudied but of considerable clinical relevance. A
      retrospective review was done using the electronic medical record database of
      Melbourne Sexual Health Centre, Australia. Cases were first presentations of
      symptomatic acute NGU with >= 5 polymorphonuclear leukocytes (PMNL)/high-powered
      field (HPF) on urethral Gram stain between January 2006 and December 2011. First
      stream urine was tested for Chlamydia trachomatis and Mycoplasma genitalium by
      PCR. Demographic, laboratory, and behavioral characteristics of cases were
      examined by univariate and multivariable analyses. Of 1,295 first presentations
      of acute NGU, 401 (32%; 95% confidence interval [CI] of 29 to 34%) had C.
      trachomatis and 134 (11%; 95% CI of 9 to 13%) had M. genitalium detected. MSM
      with acute NGU were less likely to have C. trachomatis (adjusted odds ratio [AOR]
      = 0.4; 95% CI of 0.3 to 0.6) or M. genitalium (AOR = 0.5; 95% CI of 0.3 to 0.8)
      and more likely to have idiopathic NGU (AOR = 2.4; 95% CI of 1.8 to 3.3), to
      report 100% condom use for anal/vaginal sex (AOR = 3.6; 95% CI of 2.7 to 5.0), or
      to have engaged in sexual activities other than anal/vaginal sex (AOR = 8.0; 95%
      CI of 3.6 to 17.8). Even when C. trachomatis or M. genitalium was detected, MSM
      were more likely than MSW to report consistent condom use (OR = 4.7; 95% CI of
      2.6 to 8.3). MSM with acute NGU are less likely to have the established bacterial
      sexually transmitted infections (STIs) and more likely to report protected anal
      sex or sexual activity other than anal sex prior to symptom onset than MSW. These
      data suggest that the etiologic spectrum of pathogens differs between MSM and MSW
      in acute NGU and that relatively low-risk practices are capable of inducing acute
      NGU.

PMID- 24899042
TI  - Physiological benefits of exercise in pre-dialysis chronic kidney disease.
AB  - Chronic kidney disease (CKD) is strongly associated with cardiovascular disease
      and muscle wasting, arising from numerous factors associated with declining renal
      function and lifestyle factors. Exercise has the ability to impact beneficially
      on the comorbidities associated with CKD and is accepted as an important
      intervention in the treatment, prevention and rehabilitation of other chronic
      diseases, however, the role of exercise in CKD is overlooked, with the provision
      of rehabilitation programmes well behind those of cardiology and respiratory
      services. Whilst there is now a large evidence base demonstrating the efficacy
      and safety of exercise training interventions in patients receiving dialysis, and
      this is now becoming incorporated into clinical guidelines for treatment of
      dialysis patients, there is a paucity of research evaluating the effectiveness of
      exercise in patients with CKD who are not on dialysis. Despite this, existing
      studies indicate that exercise can improve physical functioning and impact
      positively on the mediators of co-morbid diseases and upstream factors associated
      with progression of renal disease. Although preliminary evidence appears
      positive, more research is required to identify the best modes, frequency and
      intensities of exercise in order to optimise exercise prescription in pre
      dialysis CKD patients. This review summarizes what is known about the main
      effects of exercise in pre-dialysis CKD patients, discusses the potential of
      exercise in the rehabilitation and treatment of disease and highlights the need
      for further research. 

PMID- 24899043
TI  - Sarcoidosis or acute coronary syndrome: Easily distinguishable?
AB  - Sinus of Valsalva aneurysm is a rare presenting feature of ST-elevation
      myocardial infarction. We describe such a case which resolved with thrombolysis,
      and on further investigation, the patient was found to have a large sinus of
      Valsalva aneurysm. Abnormal gross pathology at the time of surgery was suspected
      to be aortitis which was only confirmed on postmortem examination 6 months later.
      We highlight the importance of working closely with a pathologist when aortitis
      is suspected, because failure to treat it medically results in a poor outcome. 

PMID- 24899044
TI  - Delayed presentation of aortoesophageal fistula after endovascular repair.
AB  - The incidence of aortoesophageal fistula after thoracic endovascular aortic
      repair has increased following an increase in thoracic endovascular aortic
      procedures. A 68-year-old man was diagnosed with aortoesophageal fistula 6 years
      after thoracic endovascular aortic repair of a descending aortic aneurysm. Due to
      massive hematemesis and instability, he underwent a left thoracotomy, graft
      repair of the aorta with stent removal, gastrostomy, and proximal esophagostomy.
      Unfortunately, he died 1 week later due to sepsis. Aortoesophageal fistula may
      present long after thoracic endovascular aortic repair, and clinicians treating
      such cases should always be aware of this complication. 

PMID- 24899045
TI  - A selection of cases of direct cannulation in surgery for type A dissection.

PMID- 24899046
TI  - A selection of cases of direct cannulation in surgery for type A dissection.

PMID- 24899047
TI  - Coding variants in TREM2 increase risk for Alzheimer's disease.
AB  - The triggering receptor expressed on myeloid 2 (TREM2) is an immune phagocytic
      receptor expressed on brain microglia known to trigger phagocytosis and regulate
      the inflammatory response. Homozygous mutations in TREM2 cause Nasu-Hakola
      disease, a rare recessive form of dementia. A heterozygous TREM2 variant, p.R47H,
      was recently shown to increase Alzheimer''s disease (AD) risk. We hypothesized
      that if TREM2 is truly an AD risk gene, there would be additional rare variants
      in TREM2 that substantially affect AD risk. To test this hypothesis, we performed
      pooled sequencing of TREM2 coding regions in 2082 AD cases and 1648 cognitively
      normal elderly controls of European American descent. We identified 16 non
      synonymous variants, six of which were not identified in previous AD studies. Two
      variants, p.R47H [P = 9.17 * 10(-4), odds ratio (OR) = 2.63 (1.44-4.81)] and
      p.R62H [P = 2.36 * 10(-4), OR = 2.36 (1.47-3.80)] were significantly associated
      with disease risk in single-variant analyses. Gene-based tests demonstrate
      variants in TREM2 are genome-wide significantly associated with AD [PSKAT-O =
      5.37 * 10(-7); OR = 2.55 (1.80-3.67)]. The association of TREM2 variants with AD
      is still highly significant after excluding p.R47H [PSKAT-O = 7.72 * 10(-5); OR =
      2.47 (1.62-3.87)], indicating that additional TREM2 variants affect AD risk.
      Genotyping in available family members of probands suggested that p.R47H (P =
      4.65 * 10(-2)) and p.R62H (P = 6.87 * 10(-3)) were more frequently seen in AD
      cases versus controls within these families. Gel electrophoresis analysis
      confirms that at least three TREM2 transcripts are expressed in human brains,
      including one encoding a soluble form of TREM2. 

PMID- 24899049
TI  - Tougu Xiaotong capsule promotes chondrocyte autophagy by regulating the Atg12/LC3
      conjugation systems.
AB  - We have previously reported that Tougu Xiaotong capsule (TXC) inhibits tidemark
      replication and cartilage degradation by regulating chondrocyte autophagy in
      vivo. Autophagy, a cell protective mechanism for maintaining cellular
      homeostasis, has been shown to be a constitutively active and protective process
      for chondrocyte survival. However, it remains unclear whether TXC promotes
      chondrocyte autophagy by regulating the autophagy-related (Atg)12/microtubule
      associated protein 1 light chain 3 (LC3) conjugation systems. Thus, in the
      present study, we investigated the effects of TXC on primary chondrocytes treated
      with cobalt chloride (CoCl2). We found that CoCl2 induced a decrease in
      chondrocyte viability and the autophagosome formation of chondrocytes, indicating
      that CoCl2 induced autophagic death in a dose- and time-dependent manner. To
      determine the effects of TXC on CoCl2-exposed chondrocytes, we assessed cell
      viability by MTT assay. Our results revealed that TXC enhanced the viability of
      CoCl2-exposed chondrocytes. To gain insight into the mechanisms responsible for
      the enhancing effects of TXC on CoCl2-exposed chondrocytes, the expression of Atg
      genes was assessed in chondrocytes exposed to CoCl2 and treated with or without
      TXC. The results revealed that the expression of beclin 1, Atg3, Atg5, Atg7,
      Atg10, Atg12 and LC3 II/LC3 I in the chondrocytes treated with TXC increased,
      compared to that in the untreated chondrocytes. In addition, ultrastructural
      analysis indicated that treated chondrocytes contained more autophagosomes than
      the untreated cells, suggesting that TXC increased the formation of
      autophagosomes in the chondrocytes to clear the CoCl2-induced autophagic death.
      Therefore, these data suggest that TXC is a potential therapeutic agent for the
      reduction of cartilage degradation that occurs in osteoarthritis.

PMID- 24899050
TI  - Use of a coccygeal axial pattern flap for reconstruction following tumour
      excision in a cat.
AB  - A 6-year-old male castrated Chartreux cat was referred for recurrence of an
      injection site sarcoma at the base of the tail 7 months after the initial
      surgery. Upon presentation, the physical examination was unremarkable except for
      a non-painful, subcutaneous mass, 2 cm in diameter, firmly attached to the
      underlying tissue on the left lateral side of the tail base. Complete blood
      count, biochemistry and urinalysis were within normal limits; thoracic
      radiographs and abdominal ultrasound showed no evidence of metastatic disease.
      After removing the mass with 3 cm margins laterally and two deep fascial planes,
      the defect was reconstructed after tail amputation using a coccygeal axial
      pattern flap based on the lateral coccygeal arteries and veins. There were no
      complications with wound healing and the only visible change was a difference in
      hair coat direction at the 1 month re-check. This is the first report to describe
      the utility and feasibility of the coccygeal axial pattern flap to reconstruct a
      large cutaneous defect over the caudodorsal pelvic region in a cat. 

PMID- 24899051
TI  - Metaphyseal osteopathy in a British Shorthair cat.
AB  - Metaphyseal osteopathy, otherwise known as hypertrophic osteodystrophy, is a
      disease that causes pyrexia and lethargy accompanied by pain in the thoracic and
      pelvic limbs of rapidly growing large-breed dogs. While metaphyseal osteopathy
      has been descibed in association with slipped capital femoral epiphysis in cats,
      it has not previously been reported as a cause of limb pain and pyrexia in this
      species. A 7-month-old British Shorthair cat presented with a 1 month history of
      pyrexia, lethargy and pain in all limbs. Investigation included radiographs of
      the limbs and chest, abdominal ultrasound, serum biochemical analysis,
      haematology, bone biopsy, joint fluid aspiration and cytology. Findings were
      consistent with a diagnosis of metaphyseal osteopathy. The cat's clinical signs
      resolved following the administration of prednisolone. Symptoms recurred 1 month
      after the cessation of prednisolone therapy, but resolved when administration was
      resumed. 

PMID- 24899053
TI  - The "Wound-QoL": a short questionnaire measuring quality of life in patients with
      chronic wounds based on three established disease-specific instruments.
AB  - The aim of this study was to develop a short questionnaire measuring health
      related quality of life (HRQoL) in chronic wounds. Three validated instruments
      assessing HRQoL in chronic wounds-the Freiburg Life Quality Assessment for
      wounds, the Cardiff Wound Impact Schedule, and the Wurzburg Wound Score-were
      completed by 154 German leg ulcer patients in a longitudinal study. For
      implementation in the new, shorter questionnaire Wound-QoL, all of those 92 items
      that covered the core content of the three questionnaires and showed good
      psychometric properties were selected. Internal consistency, convergent validity,
      and responsiveness were analyzed using the study data on the selected items (a
      new approach called virtual validation). Subscales were determined with factor
      analysis. Item, instruction, and response scale wording were harmonized.
      Seventeen items were included in the Wound-QoL, which could be attributed to
      three subscales on everyday life, body, and psyche. Both global score and
      subscale scores were internally consistent with Cronbach's alpha between 0.71 and
      0.91. The global score showed significant convergent validity (r = 0.48 to 0.69)
      and responsiveness (r = 0.18 to 0.52); the same was true for the subscale scores.
      The Wound-QoL for measurement of HRQoL in chronic wounds proved to be internally
      consistent, valid, and responsive in German leg ulcer patients. The findings of
      this virtual validation study need to be confirmed in a longitudinal validation
      study on the final Wound-QoL, which is currently being conducted. 

PMID- 24899052
TI  - Managing palliation in the neonatal unit.

PMID- 24899048
TI  - Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are
      associated with macular degeneration.
AB  - Neurodegenerative diseases affecting the macula constitute a major cause of
      incurable vision loss and exhibit considerable clinical and genetic
      heterogeneity, from early-onset monogenic disease to multifactorial late-onset
      age-related macular degeneration (AMD). As part of our continued efforts to
      define genetic causes of macular degeneration, we performed whole exome
      sequencing in four individuals of a two-generation family with autosomal dominant
      maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a
      glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing
      validated the segregation of this variant in the complete pedigree, including two
      additional affected and one unaffected individual. Sequencing of 192 maculopathy
      patients revealed additional rare variants, predicted to disrupt FBN2 function.
      We then undertook additional studies to explore the relationship of FBN2 to
      macular disease. We show that FBN2 localizes to Bruch's membrane and its
      expression appears to be reduced in aging and AMD eyes, prompting us to examine
      its relationship with AMD. We detect suggestive association of a common FBN2 non
      synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174
      controls (OR = 1.10; P-value = 3.79 * 10(-5)). Thus, it appears that rare and
      common variants in a single gene--FBN2--can contribute to Mendelian and complex
      forms of macular degeneration. Our studies provide genetic evidence for a key
      role of elastin microfibers and Bruch's membrane in maintaining blood-retina
      homeostasis and establish the importance of studying orphan diseases for
      understanding more common clinical phenotypes.

PMID- 24899054
TI  - Impact of renal medullary three-dimensional architecture on oxygen transport.
AB  - We have developed a highly detailed mathematical model of solute transport in the
      renal medulla of the rat kidney to study the impact of the structured
      organization of nephrons and vessels revealed in anatomic studies. The model
      represents the arrangement of tubules around a vascular bundle in the outer
      medulla and around a collecting duct cluster in the upper inner medulla. Model
      simulations yield marked gradients in intrabundle and interbundle interstitial
      fluid oxygen tension (PO2), NaCl concentration, and osmolality in the outer
      medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending
      limbs. In the inner medulla, where the thin ascending limbs do not mediate
      significant active NaCl transport, interstitial fluid composition becomes much
      more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a
      substantial PO2 gradient remains, owing to the relatively high oxygen demand of
      the inner medullary collecting ducts. Perhaps more importantly, the model
      predicts that in the absence of the three-dimensional medullary architecture,
      oxygen delivery to the inner medulla would drastically decrease, with the
      terminal inner medulla nearly completely deprived of oxygen. Thus model results
      suggest that the functional role of the three-dimensional medullary architecture
      may be to preserve oxygen delivery to the papilla. Additionally, a simulation
      that represents low medullary blood flow suggests that the separation of thick
      limbs from the vascular bundles substantially increases the risk of the segments
      to hypoxic injury. When nephrons and vessels are more homogeneously distributed,
      luminal PO2 in the thick ascending limb of superficial nephrons increases by 66%
      in the inner stripe. Furthermore, simulations predict that owing to the Bohr
      effect, the presumed greater acidity of blood in the interbundle regions, where
      thick ascending limbs are located, relative to that in the vascular bundles,
      facilitates the delivery of O2 to support the high metabolic requirements of the
      thick limbs and raises NaCl reabsorption.

PMID- 24899055
TI  - Gp130-dependent signaling in the podocyte.
AB  - Renal inflammation, in particular glomerular, is often characterized by increased
      IL-6 levels. The in vivo relevance of IL-6 signaling in glomerular podocytes,
      which play central roles in most glomerular diseases, is unknown. Here, we show
      that in normal mice, podocytes express gp130, the common signal-transducing
      receptor subunit of the IL-6 family of cytokines. Following systemic IL-6 or LPS
      injection in mice, podocyte IL-6 signaling was evidenced by downstream STAT3
      phosphorylation. Next, we generated mice deficient for gp130 in podocytes.
      Expectedly, these mice exhibited abrogated IL-6 downstream signaling in
      podocytes. At the age of 40 wk, they did not show spontaneous renal pathology or
      abnormal renal function. The mice were then challenged using two LPS injury
      models as well as nephrotoxic serum to induce crescentic nephritis. Under all
      conditions, circulating IL-6 levels increased markedly and the mice developed the
      pathological hallmarks of the corresponding injury models such as proteinuria and
      development of glomerular crescents, respectively. However, despite the capacity
      of normal podocytes to transduce IL-6 family signals downstream, there were no
      significant differences between mice bearing the podocyte-specific gp130 deletion
      and their control littermates in any of these models. In conclusion, under the
      different conditions tested, gp130 signaling was not a critical component of the
      (patho-)biology of the podocyte in vivo. 

PMID- 24899056
TI  - Chronic bilateral renal denervation attenuates renal injury in a transgenic rat
      model of diabetic nephropathy.
AB  - Bilateral renal denervation (BRD) has been shown to reduce hypertension and
      improve renal function in both human and experimental studies. We hypothesized
      that chronic intervention with BRD may also attenuate renal injury and fibrosis
      in diabetic nephropathy. This hypothesis was examined in a female streptozotocin
      induced diabetic (mRen-2)27 rat (TGR) shown to capture the cardinal features of
      human diabetic nephropathy. Following diabetic induction, BRD/sham surgeries were
      conducted repeatedly (at the week 3, 6, and 9 following induction) in both
      diabetic and normoglycemic animals. Renal denervation resulted in a progressive
      decrease in systolic blood pressure from first denervation to termination (at 12
      wk post-diabetic induction) in both normoglycemic and diabetic rats. Renal
      norepinephrine content was significantly raised following diabetic induction and
      ablated in denervated normoglycemic and diabetic groups. A significant increase
      in glomerular basement membrane thickening and mesangial expansion was seen in
      the diabetic kidneys; this morphological appearance was markedly reduced by BRD.
      Immunohistochemistry and protein densitometric analysis of diabetic innervated
      kidneys confirmed the presence of significantly increased levels of collagens I
      and IV, alpha-smooth muscle actin, the ANG II type 1 receptor, and transforming
      growth factor-beta. Renal denervation significantly reduced protein expression of
      these fibrotic markers. Furthermore, BRD attenuated albuminuria and prevented the
      loss of glomerular podocin expression in these diabetic animals. In conclusion,
      BRD decreases systolic blood pressure and reduces the development of renal
      fibrosis, glomerulosclerosis, and albuminuria in this model of diabetic
      nephropathy. The evidence presented strongly suggests that renal denervation may
      serve as a therapeutic intervention to attenuate the progression of renal injury
      in diabetic nephropathy. 

PMID- 24899057
TI  - Tissue-specific regulation of the mouse Pkhd1 (ARPKD) gene promoter.
AB  - Autosomal recessive polycystic kidney disease, an inherited disorder
      characterized by the formation of cysts in renal collecting ducts and biliary
      dysgenesis, is caused by mutations of the polycystic kidney and hepatic disease 1
      (PKHD1) gene. Expression of PKHD1 is tissue specific and developmentally
      regulated. Here, we show that a 2.0-kb genomic fragment containing the proximal
      promoter of mouse Pkhd1 directs tissue-specific expression of a lacZ reporter
      gene in transgenic mice. LacZ is expressed in renal collecting ducts beginning
      during embryonic development but is not expressed in extrarenal tissues. The
      Pkhd1 promoter contains a binding site for the transcription factor hepatocyte
      nuclear factor (HNF)-1beta, which is required for activity in transfected cells.
      Mutation of the HNF-1beta-binding site abolishes the expression of the lacZ
      reporter gene in renal collecting ducts. Transgenes containing the 2.0-kb
      promoter and 2.7 kb of additional genomic sequence extending downstream to the
      second exon are expressed in the kidney, intrahepatic bile ducts, and male
      reproductive tract. This pattern overlaps with the endogenous expression of Pkhd1
      and coincides with sites of expression of HNF-1beta. We conclude that the
      proximal 2.0-kb promoter is sufficient for tissue-specific expression of Pkhd1 in
      renal collecting ducts in vivo and that HNF-1beta is required for Pkhd1 promoter
      activity in collecting ducts. Additional genomic sequences located from exons 1-2
      or elsewhere in the gene locus are required for expression in extrarenal tissues.

PMID- 24899060
TI  - Assessment of renal functional maturation and injury in preterm neonates during
      the first month of life.
AB  - Worldwide, approximately 10% of neonates are born preterm. The majority of
      preterm neonates are born when the kidneys are still developing; therefore,
      during the early postnatal period renal function is likely reflective of renal
      immaturity and/or injury. This study evaluated glomerular and tubular function
      and urinary neutrophil gelatinase-associated lipocalin (NGAL; a marker of renal
      injury) in preterm neonates during the first month of life. Preterm and term
      infants were recruited from Monash Newborn (neonatal intensive care unit at
      Monash Medical Centre) and Jesse McPherson Private Hospital, respectively.
      Infants were grouped according to gestational age at birth: <=28 wk (n = 33), 29
      31 wk (n = 44), 32-36 wk (n = 32), and term (>=37 wk (n = 22)). Measures of
      glomerular and tubular function were assessed on postnatal days 3-7, 14, 21, and
      28. Glomerular and tubular function was significantly affected by gestational age
      at birth, as well as by postnatal age. By postnatal day 28, creatinine clearance
      remained significantly lower among preterm neonates compared with term infants;
      however, sodium excretion was not significantly different. Pathological
      proteinuria and high urinary NGAL levels were observed in a number of neonates,
      which may be indicative of renal injury; however, there was no correlation
      between the two markers. Findings suggest that neonatal renal function is
      predominantly influenced by renal maturity, and there was high capacity for
      postnatal tubular maturation among preterm neonates. There is insufficient
      evidence to suggest that urinary NGAL is a useful marker of renal injury in the
      preterm neonate. 

PMID- 24899061
TI  - Macroscopic electrical propagation in the guinea pig urinary bladder.
AB  - There is little knowledge about macroscopic electrical propagation in the wall of
      the urinary bladder. Recording simultaneously from a large number of
      extracellular electrodes is one technology that could be used to study the
      patterns of macroscopic electrical propagations. The urinary bladders from 14
      guinea pigs were isolated and placed in an organ bath. A 16 * 4-electrode array
      was positioned at various sites on the serosal bladder surface, and recordings
      were performed at different intravesical volumes. In four experiments, carbachol
      (CCH; 10(-6) M), nifedipine (10 mM), or tetrodotoxin (TTX; 10(-6) M) was added to
      the superfusing fluid. After the experiments, the extracellular signals were
      analyzed and propagation maps were constructed. Electrical waves were detected at
      all sites on the bladder surface and propagated for a limited distance before
      terminating spontaneously. The majority of waves (>90%) propagated in the axial
      direction (i.e., from dome to base or vice versa). An increase in vesicle volume
      significantly decreased the conduction velocity (from 4.9 +/- 1.5 to 2.7 +/- 0.7
      cm/s; P < 0.05). CCH increased, nifedipine decreased, while TTX had little effect
      on electrical activities. In addition, a new electrical phenomenon, termed a
      "patch," was discovered whereby a simultaneous electrical deflection was detected
      across an area of the bladder surface. Two types of electrical activities were
      detected on the bladder surface: 1) electrical waves propagating preferentially
      in the axial direction and 2) electrical patches. The propagating electrical
      waves could form the basis for local spontaneous contractions in the bladder
      during the filling phase. 

PMID- 24899059
TI  - ADAM17 promotes proliferation of collecting duct kidney epithelial cells through
      ERK activation and increased glycolysis in polycystic kidney disease.
AB  - Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst
      formation in the kidneys and other organs that ultimately results in kidney
      failure and death. Currently, there is no therapy for slowing down or stopping
      the progression of PKD. In this study, we identified the disintegrin
      metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney
      tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial
      cells from Ift88 degrees (rpk) mice, animal models of autosomal recessive
      polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity
      assay, and a growth factor-shedding assay in the presence or absence of the
      specific ADAM17 inhibitor TMI-005, we show that increased expression and
      activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells
      originating from the Ift88 degrees (rpk) mice (designated as PKD cells) lead to
      constitutive shedding of several growth factors, including heparin-binding EGF
      like growth factor (HB-EGF), amphiregulin, and transforming growth factor-alpha
      (TGF-alpha). Increased growth factor shedding induces activation of the
      EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells
      compared with control cells. PKD cells also displayed increased lactate formation
      and extracellular acidification indicative of aerobic glycolysis (Warburg
      effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key
      promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis
      and a proproliferative glycolytic phenotype. 

PMID- 24899063
TI  - The 13(th) meeting of the International Pituitary Pathology Society.

PMID- 24899062
TI  - Blunted renal autoregulation during high salt intake: advantageous or
      deleterious?

PMID- 24899058
TI  - APOL1 risk variants enhance podocyte necrosis through compromising lysosomal
      membrane permeability.
AB  - Development of higher rates of nondiabetic glomerulosclerosis (GS) in African
      Americans has been attributed to two coding sequence variants (G1 and G2) in the
      APOL1 gene. To date, the cellular function and the role of APOL1 variants (Vs) in
      GS are still unknown. In this study, we examined the effects of overexpressing
      wild-type (G0) and kidney disease risk variants (G1 and G2) of APOL1 in human
      podocytes using a lentivirus expression system. Interestingly, G0 inflicted
      podocyte injury only at a higher concentration; however, G1 and G2 promoted
      moderate podocyte injury at lower and higher concentrations. APOL1Vs expressing
      podocytes displayed diffuse distribution of both Lucifer yellow dye and cathepsin
      L as manifestations of enhanced lysosomal membrane permeability (LMP).
      Chloroquine attenuated the APOL1Vs-induced increase in podocyte injury,
      consistent with targeting lysosomes. The chloride channel blocker DIDS prevented
      APOL1Vs- induced injury, indicating a role for chloride influx in osmotic
      swelling of lysosomes. Direct exposure of noninfected podocytes with conditioned
      media from G1- and G2-expressing podocytes also induced injury, suggesting a
      contributory role of the secreted component of G1 and G2 as well. Adverse host
      factors (AHFs) such as hydrogen peroxide, hypoxia, TNF-alpha, and puromycin
      aminonucleoside augmented APOL1- and APOL1Vs-induced podocyte injury, while the
      effect of human immunodeficiency virus (HIV) on podocyte injury was overwhelming
      under conditions of APOLVs expression. We conclude that G0 and G1 and G2 APOL1
      variants have the potential to induce podocyte injury in a manner which is
      further augmented by AHFs, with HIV infection being especially prominent. 

PMID- 24899064
TI  - Running wheel exercise before a binge regimen of methamphetamine does not protect
      against striatal dopaminergic damage.
AB  - Repeated administration of methamphetamine (mAMPH) to rodents in a single-day
      "binge" dosing regimen produces long-lasting damage to forebrain dopaminergic
      nerve terminals as measured by decreases in tissue dopamine (DA) content and
      levels of the plasmalemmal DA transporter (DAT). However, the midbrain cell
      bodies from which the DA terminals arise survive, and previous reports show that
      striatal DA markers return to control levels by 12 months post-mAMPH, suggesting
      long-term repair or regrowth of damaged DA terminals. We previously showed that
      when rats engaged in voluntary aerobic exercise for 3 weeks before and 3 weeks
      after a binge regimen of mAMPH, exercise significantly ameliorated mAMPH-induced
      decreases in striatal DAT. However, these data left unresolved the question of
      whether exercise protected against the initial neurotoxicity from the mAMPH binge
      or accelerated the repair of the damaged DA terminals. The present experiments
      were designed to test whether exercise protects against the mAMPH-induced injury.
      Adult male Sprague-Dawley rats were allowed to run in wheels for 3 weeks before
      an acute binge regimen of mAMPH or saline, then placed into nonwheel cages for an
      additional week before autoradiographic determination of striatal DAT binding.
      The autoradiographic findings showed that prior exercise provided no protection
      against mAMPH-induced damage to striatal DA terminals. These results, together
      with analyses from our previous experiments, suggest that voluntary exercise may
      accelerate the repair of mAMPH-damaged DA terminals and that voluntary exercise
      may be useful as therapeutic adjunct in the treatment mAMPH addicts.

PMID- 24899066
TI  - Five cases of consecutive posterior (caudal) presentation of the fetus in two
      mares.

PMID- 24899065
TI  - Antibiotics used most commonly to treat animals in Europe.
AB  - The Heads of Medicines Agencies and the Federation of Veterinarians of Europe
      undertook a survey to gain an insight into European prescribing of antibiotics
      for animals, in particular to highlight the diseases for which antibiotics are
      most commonly said to be prescribed and which different classes, including human
      critically important antibiotics (CIAs). The survey was completed by 3004
      practitioners from 25 European countries. Many older antibiotics (eg,
      penicillins, tetracyclines) are cited most frequently as the prescribed classes
      to treat the main food producing species. The frequency of citation of non-CIAs
      predominates. CIAs are mostly frequently cited to be prescribed for: urinary
      diseases in cats (62 per cent), respiratory diseases in cattle (45 per cent),
      diarrhoea in cattle and pigs (respectively 29 per cent and 34 per cent),
      locomotion disorders in cattle (31 per cent), postpartum dysgalactia syndrome
      complex in pigs (31 per cent) and dental disease in dogs (36 per cent). Clear
      'preferences' between countries can be observed between antibiotic classes. The
      use of national formularies and guidance helps to drive responsible use of
      antibiotics and can significantly reduce the extent of use of CIAs. A more
      widespread introduction of veterinary practice antibiotic prescribing policies
      and monitoring obedience to these should ensure more widespread compliance with
      responsible use guidelines. 

PMID- 24899067
TI  - Dielectric properties of liquid phase molecular clusters using the external field
      method: molecular dynamics study.
AB  - We analyzed the dielectric properties of molecular liquids using the external
      field method with reaction field approximations. The applicability of this method
      to determine the dielectric properties of molecules with zero (1,4-dioxane) and
      non-zero (water and bio-molecular aqueous solutions) permanent dipole moment was
      studied. The relative static dielectric constant obtained using the external
      field method for polar and non-polar molecular liquids, including molecules with
      zero permanent dipole moment, agreed well with the experimental values presented
      in the literature. Our results indicate that the Debye relaxation time constants
      estimated from the non-equilibrium simulations using the external field method
      were accurate for molecules whose permanent dipole moments were less than 12 D. 

PMID- 24899068
TI  - Adverse drug reactions as a cause of admission to a Dublin-based university
      teaching hospital.
AB  - BACKGROUND: A meta-analysis of 25 international studies suggests that 4.2-6.0% of
      medical admissions are the result of an adverse drug reaction (ADR). One Irish
      study has found that 8.8% of admissions to a university teaching hospital were
      attributable to ADRs. AIM: To develop and evaluate a process to detect ADR
      related medical admissions to a university teaching hospital in North Dublin.
      METHODS: A screening process was developed to detect ADR-related admissions based
      on a previous Scottish study. Having evaluated the accuracy of the screening
      process in a large Dublin-based university teaching hospital, the same
      methodology was then applied to medical admissions occurring over a 9-day period.
      RESULTS: The sensitivity and specificity of the screening process were 100 and
      97%, respectively. The incidence of ADR-related hospitalization from 137
      admissions was 5.1% (95% CI 1.4-8.8%). Of the ADRs, six were type A (predictable
      and preventable) and one was a type B (uncommon ADRs) reaction. Of the seven
      ADRs, two were considered to be unavoidable while five were potentially
      avoidable. High-risk medications namely anticoagulants, antiplatelets and
      antihypertensives were identified as causative medications. CONCLUSIONS: This
      study outlines the feasibility of screening for ADR-related admission in the
      hospital setting. ADRs constitute an important and avoidable cause of hospital
      admission.

PMID- 24899071
TI  - Rapid selective electrocatalytic reduction of carbon dioxide to formate by an
      iridium pincer catalyst immobilized on carbon nanotube electrodes.
AB  - An iridium pincer dihydride catalyst was immobilized on carbon nanotube-coated
      gas diffusion electrodes (GDEs) by using a non-covalent binding strategy. The as
      prepared GDEs are efficient, selective, durable, gas permeable electrodes for
      electrocatalytic reduction of CO2 to formate. High turnover numbers (ca. 54,000)
      and turnover frequencies (ca. 15 s(-1)) were enabled by the novel electrode
      architecture in aqueous solutions saturated in CO2 with added HCO3(-).

PMID- 24899072
TI  - [Impact of chemotherapies on immunosuppression and discovery of new therapeutic
      targets].
AB  - MDSC (myeloid derived suppressor cells) are immature cells from myeloid origin
      that accumulate in spleen and tumor bed during tumor growth and that can suppress
      anti-tumor immunity by various ways. Two chemotherapeutic agents, 5-fluorouracil
      and gemcitabin, that are commonly used in the treatment of colon cancer and
      pancreatic cancer, can selectively kill MDSC. Beneficial effects of 5
      Fluorouracil and gemcitabin are however temporary. After treatment with those
      chemotherapies, an activation of the NLRP3 inflammasome is observed in MDSC, due
      to an interaction between cathepsin B and NLRP3, which leads to the production of
      IL-1beta thus increasing pro-tumor immune responses. IL-1beta enhances the
      production of IL-17 by CD4 T cells which in turn favors angiogenesis and tumor
      growth. 

PMID- 24899069
TI  - Genome-wide analysis of regulatory proteases sequences identified through
      bioinformatics data mining in Taenia solium.
AB  - BACKGROUND: Cysticercosis remains a major neglected tropical disease of humanity
      in many regions, especially in sub-Saharan Africa, Central America and elsewhere.
      Owing to the emerging drug resistance and the inability of current drugs to
      prevent re-infection, identification of novel vaccines and chemotherapeutic
      agents against Taenia solium and related helminth pathogens is a public health
      priority. The T. solium genome and the predicted proteome were reported recently,
      providing a wealth of information from which new interventional targets might be
      identified. In order to characterize and classify the entire repertoire of
      protease-encoding genes of T. solium, which act fundamental biological roles in
      all life processes, we analyzed the predicted proteins of this cestode through a
      combination of bioinformatics tools. Functional annotation was performed to yield
      insights into the signaling processes relevant to the complex developmental cycle
      of this tapeworm and to highlight a suite of the proteases as potential
      intervention targets. RESULTS: Within the genome of this helminth parasite, we
      identified 200 open reading frames encoding proteases from five clans, which
      correspond to 1.68% of the 11,902 protein-encoding genes predicted to be present
      in its genome. These proteases include calpains, cytosolic, mitochondrial signal
      peptidases, ubiquitylation related proteins, and others. Many not only show
      significant similarity to proteases in the Conserved Domain Database but have
      conserved active sites and catalytic domains. KEGG Automatic Annotation Server
      (KAAS) analysis indicated that ~60% of these proteases share strong sequence
      identities with proteins of the KEGG database, which are involved in human
      disease, metabolic pathways, genetic information processes, cellular processes,
      environmental information processes and organismal systems. Also, we identified
      signal peptides and transmembrane helices through comparative analysis with
      classes of important regulatory proteases. Phylogenetic analysis using Bayes
      approach provided support for inferring functional divergence among regulatory
      cysteine and serine proteases. CONCLUSION: Numerous putative proteases were
      identified for the first time in T. solium, and important regulatory proteases
      have been predicted. This comprehensive analysis not only complements the growing
      knowledge base of proteolytic enzymes, but also provides a platform from which to
      expand knowledge of cestode proteases and to explore their biochemistry and
      potential as intervention targets.

PMID- 24899073
TI  - Comparative genomic analysis reveals multiple long terminal repeats, lineage
      specific amplification, and frequent interelement recombination for Cassandra
      retrotransposon in pear (Pyrus bretschneideri Rehd.).
AB  - Cassandra transposable elements belong to a specific group of terminal-repeat
      retrotransposons in miniature (TRIM). Although Cassandra TRIM elements have been
      found in almost all vascular plants, detailed investigations on the nature,
      abundance, amplification timeframe, and evolution have not been performed in an
      individual genome. We therefore conducted a comprehensive analysis of Cassandra
      retrotransposons using the newly sequenced pear genome along with four other
      Rosaceae species, including apple, peach, mei, and woodland strawberry. Our data
      reveal several interesting findings for this particular retrotransposon family:
      1) A large number of the intact copies contain three, four, or five long terminal
      repeats (LTRs) (~20% in pear); 2) intact copies and solo LTRs with or without
      target site duplications are both common (~80% vs. 20%) in each genome; 3) the
      elements exhibit an overall unbiased distribution among the chromosomes; 4) the
      elements are most successfully amplified in pear (5,032 copies); and 5) the
      evolutionary relationships of these elements vary among different lineages,
      species, and evolutionary time. These results indicate that Cassandra
      retrotransposons contain more complex structures (elements with multiple LTRs)
      than what we have known previously, and that frequent interelement unequal
      recombination followed by transposition may play a critical role in shaping and
      reshaping host genomes. Thus this study provides insights into the property,
      propensity, and molecular mechanisms governing the formation and amplification of
      Cassandra retrotransposons, and enhances our understanding of the structural
      variation, evolutionary history, and transposition process of LTR
      retrotransposons in plants. 

PMID- 24899074
TI  - Simple objective detection of human lyme disease infection using immuno-PCR and a
      single recombinant hybrid antigen.
AB  - A serology-based tiered approach has, to date, provided the most effective means
      of laboratory confirmation of clinically suspected cases of Lyme disease, but it
      lacks sensitivity in the early stages of disease and is often dependent on
      subjectively scored immunoblots. We recently demonstrated the use of immuno-PCR
      (iPCR) for detecting Borrelia burgdorferi antibodies in patient serum samples
      that were positive for Lyme disease. To better understand the performance of the
      Lyme disease iPCR assay, the repeatability and variability of the background of
      the assay across samples from a healthy population (n = 36) were analyzed. Both
      of these parameters were found to have coefficients of variation of <3%. Using
      eight antigen-specific iPCR assays and positive call thresholds established for
      each assay, iPCR IgM and/or IgG diagnosis from Lyme disease patient serum samples
      (n = 12) demonstrated a strong correlation with that of 2-tier testing.
      Furthermore, a simplified iPCR approach using a single hybrid antigen and
      detecting only IgG antibodies confirmed the 2-tier diagnosis in the Lyme disease
      patient serum samples (n = 12). Validation of the hybrid antigen IgG iPCR assay
      using a blinded panel of Lyme disease and non-Lyme disease patient serum samples
      (n = 92) resulted in a sensitivity of 69% (95% confidence interval [CI], 50% to
      84%), compared to that of the 2-tier analysis at 59% (95% CI, 41% to 76%), and a
      specificity of 98% (95% CI, 91% to 100%) compared to that of the 2-tier analysis
      at 97% (95% CI, 88% to 100%). A single-tier hybrid antigen iPCR assay has the
      potential to be an improved method for detecting host-generated antibodies
      against B. burgdorferi. 

PMID- 24899075
TI  - Immunogenicity of peanut proteins containing poly(anhydride) nanoparticles.
AB  - In the last decade, peanut allergy has increased substantially. Significant
      differences in the prevalence among different countries are attributed to the
      type of thermal processing. In spite of the high prevalence and the severe
      reaction induced by peanuts, there is no immunotherapy available. The aim of this
      work was to evaluate the potential application of poly(anhydride) nanoparticles
      (NPs) as immunoadjuvants for peanut oral immunotherapy. NPs loaded with raw or
      roasted peanut proteins were prepared by a solvent displacement method and dried
      by either lyophilization or spray-drying. After physicochemical characterization,
      their adjuvant capacity was evaluated after oral immunization of C57BL/6 mice.
      All nanoparticle formulations induced a balanced T(H)1 and T(H)2 antibody
      response, accompanied by low specific IgE induction. In addition, oral
      immunization with spray-dried NPs loaded with peanut proteins was associated with
      a significant decrease in splenic T(H)2 cytokines (interleukin 4 [IL-4], IL-5,
      and IL-6) and enhancement of both T(H)1 (gamma interferon [IFN-gamma]) and
      regulatory (IL-10) cytokines. In conclusion, oral immunization with
      poly(anhydride) NPs, particularly spray-dried formulations, led to a pro-T(H)1
      immune response.

PMID- 24899076
TI  - Effectiveness of nurse-practitioner-delivered brief motivational intervention for
      young adult alcohol and drug use in primary care in South Africa: a randomized
      clinical trial.
AB  - AIMS: To assess the effectiveness of brief motivational intervention for alcohol
      and drug use in young adult primary care patients in a low-income population and
      country. METHODS: A randomized controlled trial in a public-sector clinic in
      Delft, a township in the Western Cape, South Africa recruited 403 patients who
      were randomized to either single-session, nurse practitioner-delivered Brief
      Motivational Intervention plus referral list or usual care plus referral list,
      and followed up at 3 months. RESULTS: Although rates of at-risk alcohol use and
      drug use did not differ by treatment arm at follow-up, patients assigned to the
      Brief Motivational Intervention had significantly reduced scores on ASSIST
      (Alcohol, Smoking and Substance Involvement Screening Test) for alcohol-the most
      prevalent substance. CONCLUSION: Brief Motivational Intervention may be effective
      at reducing at-risk alcohol use in the short term among low-income young adult
      primary care patients; additional research is needed to examine long-term
      outcomes.

PMID- 24899078
TI  - Identification of 32 major histocompatibility complex class I alleles in African
      green monkeys.
AB  - The African green monkey may be an ideal replacement for the rhesus monkey in
      biomedical research, but relatively little is known about the genetic background
      of major histocompatibility complex (MHC) class I molecules. In analysis of 12
      African green monkeys, 13 Chae-A and 19 Chae-B alleles were identified. Among
      these alleles, 12 Chae-A and 9 Chae-B were new lineages. The full amino acid
      length deduced for Chae-A genes is 365 amino acids, but for Chae-B genes, the
      lengths are 365, 362, 361, and 359 amino acids, respectively. There were 1-3 Chae
      A alleles and 2-5 Chae-B alleles in each animal. In African green monkeys, rhesus
      monkeys, and cynomolgus monkeys, the MHC-A and MHC-B alleles display trans
      species polymorphism, rather than being clustered in a species-specific fashion. 

PMID- 24899079
TI  - GlasgowComa Scale 40 years later: in need of recalibration?

PMID- 24899077
TI  - H2O2 mediates the crosstalk of brassinosteroid and abscisic acid in tomato
      responses to heat and oxidative stresses.
AB  - The production of H2O2 is critical for brassinosteroid (BR)- and abscisic acid
      (ABA)-induced stress tolerance in plants. In this study, the relationship between
      BR and ABA in the induction of H2O2 production and their roles in response to
      heat and paraquat (PQ) oxidative stresses were studied in tomato. Both BR and ABA
      induced increases in RBOH1 gene expression, NADPH oxidase activity, apoplastic
      H2O2 accumulation, and heat and PQ stress tolerance in wild-type plants. BR could
      only induced transient increases in these responses in the ABA biosynthetic
      mutant notabilis (not), whereas ABA induced strong and prolonged increases in
      these responses in the BR biosynthetic mutant d (^im) compared with wild-type
      plants. ABA levels were reduced in the BR biosynthetic mutant but could be
      elevated by exogenous BR. Silencing of RBOH1 compromised BR-induced apoplastic
      H2O2 production, ABA accumulation, and PQ stress responses; however, ABA-induced
      PQ stress responses were largely unchanged in the RBOH1-silenced plants. BR
      induces stress tolerance involving a positive feedback mechanism in which BR
      induces a rapid and transient H2O2 production by NADPH oxidase. The process in
      turn triggers increased ABA biosynthesis, leading to further increases in H2O2
      production and prolonged stress tolerance. ABA induces H2O2 production in both
      the apoplastic and chloroplastic compartments. 

PMID- 24899081
TI  - Identification of interspecific differences in phase II reactions: determination
      of metabolites in the urine of 16 mammalian species exposed to environmental
      pyrene.
AB  - Interspecific differences in xenobiotic metabolism are a key to determining
      relative sensitivities of animals to xenobiotics. However, information on
      domesticated livestock, companion animals, and captive and free-ranging wildlife
      is incomplete. The present study evaluated interspecific differences in phase II
      conjugation using pyrene as a nondestructive biomarker of polycyclic aromatic
      hydrocarbon (PAH) exposure. Polycyclic aromatic hydrocarbons and their
      metabolites have carcinogenic and endocrine-disrupting effects in humans and
      wildlife and can have serious consequences. The authors collected urine from 16
      mammalian species and analyzed pyrene metabolites. Interspecific differences in
      urinary pyrene metabolites, especially in the concentration and composition of
      phase II conjugated metabolites, were apparent. Glucuronide conjugates are
      dominant metabolites in the urine of many species, including deer, cattle, pigs,
      horses, and humans. However, they could not be detected in ferret urine even
      though the gene for ferret Uridine 5'-diphospho-glucuronosyltransferase (UDP
      glucuronosyltransferase, UGT) 1A6 is not a pseudogene. Sulfate conjugates were
      detected mainly in the urine of cats, ferrets, and rabbits. Interestingly,
      sulfate conjugates were detected in pig urine. Although pigs are known to have
      limited aryl sulfotransferase activity, the present study demonstrated that pig
      liver was active in 1-hydroxypyrene sulfation. The findings have some application
      for biomonitoring environmental pollution.

PMID- 24899082
TI  - Polymorphisms in cyclooxygenase-2 gene and risk of developing coal workers'
      pneumoconiosis: a case-control study.
AB  - BACKGROUND: Coal workers' pneumoconiosis (CWP) is characterized by progressive
      pulmonary fibrosis. Inflammation is crucial in the host response to silica and it
      contributes to pulmonary fibrosis. Cyclooxygenase-2 is involved in this process.
      The association between single-nucleotide polymorphisms in cyclooxygenase-2 gene
      with pneumoconiosis risk was investigated. METHODS: An association study was
      conducted by analyzing two single-nucleotide polymorphisms of cyclooxygenase-2
      (rs689466 and rs20417) in a case-control study involving 90 patients and 90
      healthy individuals (controls). Genotyping was performed by the TaqMan method.
      RESULTS: The rs689466 AG and GG and rs689466 GC polymorphisms were significantly
      less frequent in patients than in controls. Cyclooxygenase-2 rs689466 and rs20417
      variant genotypes exhibited 21% and 12% decreased CWP risk, respectively.
      CONCLUSION: Cyclooxygenase-2 rs689466 and rs20417 polymorphisms were associated
      with CWP risk.

PMID- 24899080
TI  - Nutritional profile of Indian vegetarian diets--the Indian Migration Study (IMS).
AB  - BACKGROUND: The cardiovascular and other health benefits and potential harms of
      protein and micronutrient deficiency of vegetarian diets continue to be debated.
      METHODS: Study participants included urban migrants, their rural siblings and
      urban residents (n = 6555, mean age - 40.9 yrs) of the Indian Migration Study
      from Lucknow, Nagpur, Hyderabad and Bangalore. Information on diet (validated
      interviewer-administered semi-quantitative food frequency questionnaire),
      tobacco, alcohol, physical activity, medical histories, as well as blood
      pressure, fasting blood and anthropometric measurements were collected. Nutrient
      databases were used to calculate nutrient content of regional recipes.
      Vegetarians ate no eggs, fish, poultry and meat. Using multivariate linear
      regression with robust standard error model, we compared the macro- and micro
      nutrient profile of vegetarian and non-vegetarian diets. RESULTS: Vegetarians,
      (32.8% of the population), consumed greater amounts of legumes, vegetables, roots
      and tubers, dairy and sugar, while non-vegetarians had a greater intake of
      cereals, fruits, spices, salt (p < 0.01), fats and oils. Vegetarians had a higher
      socioeconomic status, and were less likely to smoke, drink alcohol (p < 0.0001)
      and engage in less physical activity (p = 0.04). On multivariate analysis,
      vegetarians consumed more carbohydrates (beta = 7.0 g/day (95% CI: 9.9 to 4.0), p
      < 0.0001), vitamin C (beta = 8.7 mg/day (95% CI: 4.3 to13.0), p < 0.0001) and
      folate (beta = 8.0 mcg/day (95% CI: 3.3 to 12.7), p = 0.001) and lower levels of
      fat (beta = -1.6 g/day (95% CI: -0.62 to -2.7), p = 0.002), protein (beta = -6.4
      g/day (95% CI: -5.8 to -7.0), p < 0.0001), vitamin B12 (beta = -1.4 mcg/day (95%
      CI: -1.2 to -1.5), p < 0.0001) and zinc (beta = -0.6 mg/day (95% CI: -0.4 to 
      0.7), p < 0.0001). CONCLUSION: Overall, Indian vegetarian diets were found to be
      adequate to sustain nutritional demands according to recommended dietary
      allowances with less fat. Lower vitamin B12 bio-availability remains a concern
      and requires exploration of acceptable dietary sources for vegetarians.

PMID- 24899083
TI  - The influence of diabetes severity on receipt of guideline-concordant treatment
      for breast cancer.
AB  - Diabetes severity may influence breast cancer treatment choices. We examined
      whether receipt of guideline-concordant breast cancer treatment varied with
      diabetes severity. Cancer registry data from seven states regarding 6,912 stage I
      III breast cancers were supplemented by medical record abstraction and physician
      verification. We used logistic regression models to examine associations of
      diabetes severity with guideline-concordant locoregional treatment, adjuvant
      chemotherapy, and hormonal therapy adjusted for sociodemographics, comorbidity,
      and tumor characteristics. We defined guideline concordance using National
      Comprehensive Cancer Network guidelines, and diabetes and comorbidities using the
      Adult Comorbidity Evaluation-27 index. After adjustment, there was significant
      interaction of diabetes severity with age for locoregional treatment (p = 0.001),
      with many diabetic women under age 70 less frequently receiving guideline
      concordant treatment than non-diabetic women. Among similarly aged women,
      guideline concordance was lower for women with mild diabetes in their late
      fifties through mid-sixties, and with moderate/severe diabetes in their late
      forties to early sixties. Among women in their mid-seventies to early eighties,
      moderate/severe diabetes was associated with increased guideline concordance. For
      adjuvant chemotherapy, moderate/severe diabetes was less frequently associated
      with guideline concordance than no diabetes [OR 0.58 (95 % CI 0.36-0.94)].
      Diabetes was not associated with guideline-concordant hormonal treatment (p =
      0.929). Some diabetic women were less likely to receive guideline-concordant
      treatment for stage I-III breast cancer than non-diabetic women. Diabetes
      severity was associated with lower guideline concordance for locoregional
      treatment among middle-aged women, and lower guideline concordance for adjuvant
      chemotherapy. Differences were not explained by comorbidity and may contribute to
      potentially worse breast cancer outcomes. 

PMID- 24899084
TI  - A retrospective study evaluating a fixed low dose capecitabine monotherapy in
      women with HER-2 negative metastatic breast cancer.
AB  - To determine if a low fixed dosing strategy of capecitabine would produce
      comparable clinical activity with less adverse toxicities compared to published
      data with higher doses in the setting of metastatic breast cancer (mBC). We
      retrospectively analyzed patients treated with a low fixed dose of capecitabine
      (CAPE-L) at 1,000 mg twice daily for 14 days every 21 days. Outcomes included
      clinical benefit rate (CBR), overall response rates (ORR), time to progression
      (TTP), and overall survival (OS). A historical comparison group of mBC patients
      treated on 12 prior trials at the package-insert dose of capecitabine (n = 1,949)
      was utilized. Eighty-six patients were analyzed in our cohort. Positive hormone
      receptor status (79.1 vs. 50.6 %), and capecitabine as first-line chemotherapy
      (44.2 vs. 16.5 %) were more frequent in our cohort relative to the historical
      comparison. The median starting dose in our cohort was 633.5 mg/m(2). The CBR was
      similar between the CAPE-L and the standard dose cohorts (55.8 vs. 49.5 %), as
      was ORR (24.3 vs. 24 %), and median TTP (7 mo, 95 % CI 5.5-8.5 vs. 5.1 mo, 95 %
      CI 4.5-5.7). Median OS was longer in our cohort (24 mo, 95 % CI 16.8-31.2) than
      the historic standard dose cohort (12.1 mo, 95 % CI 9.6-14.4), a difference that
      was likely explained by the higher proportion of patients in the CAPE-L cohort
      who received capecitabine as first-line chemotherapy and who had hormone receptor
      positive disease. As expected, adverse events were less frequent with CAPE-L. We
      found that CAPE-L, which translates into a dose of 600-650 mg/m(2), appeared to
      have good clinical efficacy and acceptable toxicity. 

PMID- 24899085
TI  - Poor responders and androgen adjuvant treatment: "Still haven't found what I'm
      looking for...".

PMID- 24899087
TI  - Editor's comment on 'Response: The timing of monozygotic twinning: a pro-life
      challenge to conventional scientific wisdom'.

PMID- 24899086
TI  - Response: The timing of monozygotic twinning: a pro-life challenge to
      conventional scientific wisdom.

PMID- 24899088
TI  - No Increase in Female Breast Size or Fat Redistribution to the Upper Body After
      Liposuction: A Prospective Controlled Photometric Study.
AB  - BACKGROUND: Some studies have indicated that liposuction may cause breast
      enlargement. Fat redistribution to the upper body as a compensatory mechanism
      after liposuction has also been reported. OBJECTIVES: To evaluate the possibility
      of secondary breast hypertrophy and fat redistribution after liposuction, breast
      size and upper body measurements were obtained and compared for women who did not
      gain weight postoperatively. METHODS: Eighty-two women who underwent cosmetic
      surgery, not including breast surgery, were enrolled in this prospective
      controlled study. Participants represented 1 of 3 procedure groups: cosmetic
      surgery not including liposuction (n = 24), liposuction (n = 41), and liposuction
      combined with abdominoplasty (n = 17). Breast measurements were obtained from
      standardized lateral photographs matched for size and orientation. Results were
      compared among the study groups. RESULTS: Postoperatively, there were no
      significant changes in mean body weight among the study groups. No significant
      increases in upper pole projection, breast projection, or breast area were found
      in patients treated with liposuction alone and those who received liposuction
      plus abdominoplasty. Upper body dimensions were unchanged except for a
      significant (P < .01) decrease in upper abdominal width in women treated with
      liposuction plus abdominoplasty. The findings were the same for a subset of 17
      women with liposuction aspirate volumes >1500 mL. CONCLUSIONS: Results indicate
      that neither liposuction nor abdominoplasty produces secondary breast
      enlargement. Upper body dimensions are unchanged, consistent with findings of a
      previous study and contrary to the theory of fat redistribution. LEVEL OF
      EVIDENCE: 2.

PMID- 24899090
TI  - Response to letter to the editor on skin manifestations of celiac disease: not
      always dermatitis herpetiformis.

PMID- 24899091
TI  - Prevention of pacemaker-associated contact dermatitis by polytetrafluoroethylene
      sheet and conduit coating of the pacemaker system.
AB  - A 73-year-old female with sick sinus syndrome and atrial fibrillation was
      implanted with a ventricular demand inhibit pacemaker. She subsequently developed
      multiple episodes of skin irritation and necrosis. Skin patch testing revealed
      sensitivity to almost every component of the pacemaker system. The pacemaker was
      removed and replaced with a new pacemaker in which the generator was covered with
      a polytetrafluoroethylene (PTFE) sheet and the lead was covered with PTFE
      conduit. The patient suffered no further episodes of pacemaker-associated contact
      dermatitis. 

PMID- 24899093
TI  - The cardiovascular effects of insulin.
AB  - INTRODUCTION: Cardiovascular disease remains one of the leading causes of
      morbidity and mortality in diabetes mellitus. A causal link between insulin,
      atherosclerosis and cardiovascular risk has been investigated at the basic
      science level and studied in large clinical trials. AREAS COVERED: The
      cardiovascular actions of insulin and its role at the level of the endothelium
      will be reviewed. Cardiovascular outcomes in several large diabetes trials where
      insulin management was prominent will be summarized. EXPERT OPINION: The vascular
      actions of insulin are complex and mediated primarily via nitric oxide and
      endothelin-1. It appears that insulin resistance, rather than hyperinsulinemia
      itself, increases cardiovascular risk. In fact, hyperinsulinemia in the setting
      of normal beta cell function protects obese and insulin-resistant individuals
      from type 2 diabetes. Large clinical trials have supported that insulin
      management is not associated with increased adverse outcomes. A multifactorial
      approach targeting modifiable risk factors, including smoking cessation, blood
      pressure and lipid management, reduces cardiovascular risk. Therapy goals should
      be individualized and hypoglycemia, especially in individuals receiving insulin
      management, should be strictly avoided.

PMID- 24899092
TI  - Poor predictive value of contemporary bleeding risk scores during long-term
      treatment of venous thromboembolism. A multicentre retrospective cohort study.
AB  - Bleeding is a common and feared complication of oral anticoagulant therapy.
      Several prediction models have been recently developed, but there is a lack of
      evidence in patients with venous thromboembolism (VTE). The aim of this study was
      to validate currently available bleeding risk scores during long-term oral
      anticoagulation for VTE. We retrospectively included adult patients on vitamin K
      antagonists for VTE secondary prevention, followed by five Italian
      Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between
      January 2010 and August 2012. All bleeding events were classified as major
      bleeding (MB) or clinically-relevant-non-major-bleeding (CRNMB). A total of 681
      patients were included (median age 63 years; 52.0% female). During a mean follow
      up of 8.82 (+/- 3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB),
      for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding
      was higher in the first three months of treatment (15.86/100 patient-years) than
      afterwards (7.13/100 patient-years). The HAS-BLED showed the best predictive
      value for bleeding complications during the first three months of treatment (area
      under the curve [AUC] 0.68, 95% confidence interval [CI] 0.59-0.78), while only
      the ACCP score showed a modest predictive value after the initial three months
      (AUC 0.61, 95%CI 0.51-0.72). These two scores had also the highest sensitivity
      and the highest negative predictive value. None of the scores predicted MB better
      than chance. Currently available bleeding risk scores had only a modest
      predictive value for patients with VTE. Future studies should aim at the creation
      of a new prediction rule, in order to better define the risk of bleeding of VTE
      patients. 

PMID- 24899096
TI  - Reply: To PMID 24383670.

PMID- 24899095
TI  - Synergic effect of exercise and lipoic acid on protection against kainic acid
      induced seizure activity and oxidative stress in mice.
AB  - Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred
      to as thioctic acid with antioxidant activity, were investigated using chemical
      induced seizure model. We investigated the synergic effect of physical exercise
      and LA on kainic acid-induced seizure activity caused by oxidative stress. After
      8 weeks of swimming training, body weight decreased and endurance capacity
      increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.)
      evoked seizure activity 5 min after injection, and seizure activity peaked
      approximately 80 min after kainic acid treatment. Median seizure activity score
      in KA only treated group was 4.55 (range 0.5-5), 3.45 for "LA + KA" group (range
      0.5-4.3), 3.12 for "EX + KA" group (range 0.05-3.4, p < 0.05 vs. "KA only"
      group), 2.13 for "EX + LA + KA" group (range 0.5-3.0, p < 0.05 vs. "EX + KA"
      group). Also, there was a synergic cooperation of exercise and LA in lowering the
      mortality in kainic acid treated mice (chi2 = 5.45, p = 0.031; "EX + KA" group
      vs. "LA + EX + KA" group). In addition, the synergic effect of exercise and LA
      was found in PGx activity compared to separated treatment ("LA + EX + KA": 37.3
      +/- 1.36; p < 0.05 vs. "LA + KA" and "EX + KA" group). These results indicate
      that physical exercise along with LA could be a more efficient method for
      modulating seizure activity and oxidative stress.

PMID- 24899094
TI  - Neurotrophic factors, clinical features and gender differences in depression.
AB  - Recent studies have evaluated the role of brain-derived neurotrophic factor
      (BDNF) in mood disorders; however, little is known about alterations in nerve
      growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). The
      aim of this study was to evaluate differences among serum neurotrophic factors
      (BDNF, NGF and GDNF) in depressed patients and healthy controls and to verify the
      association between serum neurotrophic levels and clinical characteristics in a
      young, depressed population stratified by gender. This is a cross-sectional study
      with depressed patients and population controls 18-29 years of age. The
      concentrations of neurotrophic factors were determined by the ELISA method. The
      diagnosis of depression and the duration of the disease were assessed by the
      Structured Clinical Interview according to the diagnostic and statistical manual
      of mental disorders. Depression severity was measured with the 17-item Hamilton
      Rating Scale for Depression, and the severity of anxiety symptoms was measured
      using the Hamilton Anxiety Rating Scale. Serum BDNF and GDNF were lower in major
      depressive disorder (MDD) patients compared to controls (p <= 0.001). Serum NGF
      levels were higher in MDD patients versus controls (p <= 0.001). BDNF was
      associated with the duration of disease only in women (p = 0.005). GDNF was not
      associated with clinical characteristics in either gender. In women, NGF was
      associated with the severity of depressive symptoms (p = 0.009), anxiety (p =
      0.011) and disease duration (p = 0.005). NGF was associated with disease duration
      in men (p = 0.026). Our results demonstrated that significant neurochemical
      differences in NGF and BDNF, but not in GDNF, were associated with the clinical
      features of MDD when patients were stratified by gender. 

PMID- 24899097
TI  - Chromogranins can be measured in samples from cats and dogs.
AB  - BACKGROUND: Methods for objective evaluation of stress in animals are important,
      but clinically difficult. An alternative method to study the sympathetic activity
      may be to investigate Chromogranin A (CGA), Chromogranin B (CGB) and
      Secretogranin II (SG2). The aim of this study was to investigate the cross
      reactivity of CGA, CGB and SG2 between man, cat and dog and to explore
      possibilities to measure these proteins in samples from cats and dogs. RESULTS:
      Adrenal gland extracts from feline and canine species were measured by region
      specific radioimmunoassays in different dilution steps to explore possible inter
      species cross reactivity. High cross reactivity was found for cats in the CGA17
      38, CGA324-337, CGA361-372, CGB and SG2 assays. High cross reactivity was found
      for dogs in the CGA17-38, CGA361-372, CGB and SN assays. The method measuring the
      intact CGA was not useful for measurements in cats and dogs. CONCLUSIONS: Region
      specific assays measuring defined parts of CGA, CGB and SG2 can be used for
      measurements in samples from cats and dogs. These results are promising and will
      allow for further studies of these proteins as possible clinical biomarkers in
      cats and dogs.

PMID- 24899098
TI  - Bax inhibitor-1-mediated inhibition of mitochondrial Ca2+ intake regulates
      mitochondrial permeability transition pore opening and cell death.
AB  - A recently studied endoplasmic reticulum (ER) stress regulator, Bax inhibitor-1
      (BI-1) plays a regulatory role in mitochondrial Ca(2+) levels. In this study, we
      identified ER-resident and mitochondria-associated ER membrane (MAM)-resident
      populations of BI-1. ER stress increased mitochondrial Ca(2+) to a lesser extent
      in BI-1-overexpressing cells (HT1080/BI-1) than in control cells, most likely as
      a result of impaired mitochondrial Ca(2+) intake ability and lower basal levels
      of intra-ER Ca(2+). Moreover, opening of the Ca(2+)-induced mitochondrial
      permeability transition pore (PTP) and cytochrome c release were regulated by BI
      1. In HT1080/BI-1, the basal mitochondrial membrane potential was low and also
      resistant to Ca(2+) compared with control cells. The activity of the
      mitochondrial membrane potential-dependent mitochondrial Ca(2+) intake pore, the
      Ca(2+) uniporter, was reduced in the presence of BI-1. This study also showed
      that instead of Ca(2+), other cations including K(+) enter the mitochondria of
      HT1080/BI-1 through mitochondrial Ca(2+)-dependent ion channels, providing a
      possible mechanism by which mitochondrial Ca(2+) intake is reduced, leading to
      cell protection. We propose a model in which BI-1-mediated sequential regulation
      of the mitochondrial Ca(2+) uniporter and Ca(2+)-dependent K(+) channel opening
      inhibits mitochondrial Ca(2+) intake, thereby inhibiting PTP function and leading
      to cell protection. 

PMID- 24899099
TI  - The effects of calcitonin on the development of and Ca2+ levels in heat-shocked
      bovine preimplantation embryos in vitro.
AB  - Intracellular calcium homeostasis is essential for proper cell function. We
      investigated the effects of heat shock on the development of and the
      intracellular Ca2+ levels in bovine preimplantation embryos in vitro and the
      effects of calcitonin (CT), a receptor-mediated Ca2+ regulator, on heat shock
      induced events. Heat shock (40.5 C for 10 h between 20 and 30 h postinsemination)
      of in vitro-produced bovine embryos did not affect the cleavage rate; however, it
      significantly decreased the rates of development to the 5- to 8-cell and
      blastocyst stages as compared with those of the control cultured for the entire
      period at 38.5 C (P < 0.05). The relative intracellular Ca2+ levels at the 1-cell
      stage (5 h after the start of heat shock), as assessed by Fluo-8 AM, a
      fluorescent probe for Ca2+, indicated that heat shock significantly lowered the
      Ca2+ level as compared with the control level. Semiquantitative reverse
      transcription PCR and western blot analyses revealed the expression of CT
      receptor in bovine preimplantation embryos. The addition of CT (10 nM) to the
      culture medium ameliorated the heat shock-induced impairment of embryonic
      development beyond the 5- to 8-cell stage. The Ca2+ level in the heat-shocked
      embryos cultured with CT was similar to that of the control embryos, suggesting
      that heat shock lowers the Ca2+ level in fertilized embryos in vitro and that a
      lower Ca2+ level is implicated in heat shock-induced impairment of embryonic
      development. Intracellular Ca2+ -mobilizing agents, e.g., CT, may effectively
      circumvent the detrimental effects of heat shock on early embryonic development.

PMID- 24899101
TI  - Osteoporosis treatment disparities: a 6-year aggregate analysis from national
      survey data.
AB  - We studied factors to determine the receipt of osteoporosis treatment in
      individuals with osteoporosis. Treatment was associated with age, gender, race,
      body mass index (BMI), family history, arthritis and thyroid problems, daily
      glucocorticoid use, number of prescriptions and healthcare visits, and insurance
      type. INTRODUCTION: Osteoporosis is underrecognized and undertreated. Few studies
      have examined factors associated with osteoporosis treatment in a large, national
      sample of men and women. METHODS: We aggregated National Health and Nutrition
      Examination Survey (NHANES) data from 2005 to 2010 and created a subsample which
      included individuals 50 years or older who were identified to have osteoporosis
      either by self-report data or by bone density measurements. The primary outcome
      was the receipt of osteoporosis treatment either from self-report or from
      prescription records. Covariates included sociodemographics, clinical
      characteristics, and access to healthcare variables. Logistic regression analyses
      were performed to determine factors that associate with osteoporosis treatment.
      RESULTS: From a sample of 31,0134 participants, 1,133 subjects (3.65 %) met the
      study criteria. Treatment was associated with age (odds ratio (OR) = 1.14),
      gender (OR = 13.25), race (OR = 2.23, White vs. Black; OR = 1.76, other vs.
      Black), BMI (OR = 1.67, normal vs. obese; OR = 2.68, overweight vs. obese),
      family history of osteoporosis (OR = 1.94), arthritis (OR = 1.43), daily
      glucocorticoid use (OR = 1.43), number of prescriptions (OR = 1.01), and number
      of healthcare visits in the past year (OR = 1.44, 4-9 vs. 0-3 visits). All odds
      ratios were statistically significant. CONCLUSION: A large number of individuals
      diagnosed with osteoporosis above the age of 50 remain untreated. It is important
      for healthcare providers to better assess older adults with osteoporosis,
      including individuals who frequently receive medical care.

PMID- 24899100
TI  - Plasmid-based Stat3-specific siRNA and GRIM-19 inhibit the growth of thyroid
      cancer cells in vitro and in vivo.
AB  - It has been shown that overexpression of signal transducer and activator of
      transcription 3 (Stat3) contribute to the progression and metastasis of various
      solid tumors and that silencing Stat3 inhibits tumor growth in several types of
      cancer. Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), a Stat3
      inhibitory protein, was identified as a potential tumor suppressor associated
      with growth inhibition and cell apoptosis by targeting the transcription factor
      Stat3 for inhibition. However, little is known about Stat3 and GRIM-19 roles in
      the tumor growth of thyroid carcinoma cells. In the present study, we developed a
      dual expression plasmid that co-expressed Stat3-specific siRNA and GRIM-19 (pSi
      Stat3-GRIM-19) and transfected it into SW579 cells (thyroid carcinoma cell line)
      to evaluate its effects on cell proliferation, cell apoptosis, cell migration and
      cell invasion in vitro and tumor growth in vivo. Simultaneous expression of pSi
      Stat3-GRIM-19 in SW579 cancer cells was found to significantly suppress the
      proliferation, migration and invasion in vitro and tumor growth in vivo, when
      compared to the controls either Stat3-specific siRNA or GRIM-19 alone. In
      conclusion, our data demonstrated that a combined strategy of co-expressed Stat3
      specific siRNA and GRIM19 synergistically and more effectively suppressed thyroid
      tumor growth, and have therapeutic potential for the treatment of thyroid cancer.

PMID- 24899102
TI  - Efficacy of zoledronic acid treatment in Paget disease of bone.
AB  - Clinical trials have shown that zoledronic acid was more effective than other
      bisphosphonates in the treatment of Paget disease. We retrospectively reviewed
      remission and relapse statuses of 12 patients with Paget disease. Remission was
      achieved in all patients after treatment. We recommend zoledronic acid in the
      first-line treatment of Paget disease. INTRODUCTION: Paget disease is a disease
      of bone of unknown etiology with increased bone turnover that results in
      defective bone microarchitecture and bone deformity. Bisphosphonates are used in
      symptomatic Paget disease of bone. Clinical trials have shown that zoledronic
      acid was more effective than other bisphosphonates in the treatment of Paget
      disease. METHODS: In this study, we retrospectively reviewed the remission and
      relapse statuses of 12 patients with Paget disease of bone who were seen as
      outpatients between October 2011 and October 2013.We evaluated alkaline
      phosphates, osteocalcin, and deoxypyridinoline levels measured before and at 6th,
      12th, and 18th months of treatment. RESULTS: Pretreatment and posttreatment
      values for alkaline phosphates, deoxypyridinoline, and osteocalcin were as
      follows: 473 +/- 256 U/L, 14.99 +/- 7.63 mmol/L, 21.09 +/- 3.18 ng/ml, and 82 +/-
      13 U/L, 5.14 +/- 1.11 mmol/L, and 8.57 +/- 4.31 ng/ml. Remission was achieved in
      all patients after treatment. The levels indicated that remission continued at
      12th and 18th months of treatment. There was statistically significant difference
      between pretreatment and posttreatment values. No statistically significant
      difference between the levels measured at 6th, 12th, and 18th months of treatment
      was detected. CONCLUSION: We recommend zoledronic acid in the first-line
      treatment of Paget disease of bone in achieving and maintaining remission.

PMID- 24899106
TI  - Extreme surface propensity of halide ions in water.
AB  - Water possesses an extremely high polarity, making it a unique solvent for salts.
      Indeed, aqueous electrolyte solutions are ubiquitous in the atmosphere, biology,
      energy applications and industrial processes. For many processes, chemical
      reactions at the water surface are rate determining, and the nature and
      concentration of the surface-bound electrolytes are of paramount importance, as
      they determine the water structure and thereby surface reactivity. Here we
      investigate the dynamics of water molecules at the surface of sodium chloride and
      sodium iodide solutions, using surface-specific femtosecond vibrational
      spectroscopy. We quantify the interfacial ion density through the reduced energy
      transfer rates between water molecules resulting from the lowered effective
      interfacial density of water molecules, as water is displaced by surface active
      ions. Our results reveal remarkably high surface propensities for halogenic
      anions, higher for iodide than for chloride ions, corresponding to surface ion
      concentrations several times that of the bulk. 

PMID- 24899103
TI  - Clinical efficacy and treatment persistence of monthly minodronate for
      osteoporotic patients unsatisfied with, and shifted from, daily or weekly
      bisphosphonates: the BP-MUSASHI study.
AB  - This multi-center, prospective, open-label, observational study evaluated the
      effects of once-monthly minodronate (50 mg) on treatment persistence, bone
      turnover markers, bone mineral density, low back pain, and upper gastrointestinal
      symptoms in outpatients with osteoporosis previously treated with daily or weekly
      bisphosphonate products. INTRODUCTION: The purposes of this study were to
      investigate the effects of once-monthly oral minodronate (MIN 50 mg) on bone
      turnover markers and bone mineral density, low back pain, and upper
      gastrointestinal symptoms, as well as preference for and treatment persistence of
      MIN 50 mg among Japanese osteoporosis patients currently treated with daily or
      weekly bisphosphonates. METHODS: Study patients were allocated based on their
      preference to either the Switch group (patients willing to switch over to MIN 50
      mg) or the Continue group (patients wanting to continue their current therapies).
      Patients' treatment persistence and satisfaction levels with the therapies were
      assessed using a self-administered questionnaire. The study endpoints were serum
      TRACP-5b, serum P1NP, bone mineral density, upper gastrointestinal symptoms, and
      low back pain. RESULTS: In total, 264 and 133 patients were allocated into the
      Switch and Continue groups, respectively. Approximately, 65 % of patients were
      willing to switch to MIN 50 mg, with the predominant reason being "less frequent
      dosing more convenient." Treatment persistence was significantly higher in the
      Switch group (MIN 50 mg) than the Continue group. Almost all patients with
      abnormal bone metabolism markers demonstrated normalization after switchover. MIN
      50 mg alleviated low back pain and upper gastrointestinal symptoms induced by
      prior bisphosphonate use. CONCLUSIONS: MIN 50 mg alleviates low back pain,
      reduces bone turnover markers and increases bone density, and induces fewer upper
      gastrointestinal symptoms after switchover from prior bisphosphonate products,
      and therefore, it may provide patients with a more convenient treatment option
      and enhance long-term treatment persistence.

PMID- 24899104
TI  - Patterns of treatment among a cohort of older low-income adults starting new
      medications for osteoporosis.
AB  - Among 125,954 new users of osteoporosis (OP) medications, 77 % of subjects
      stopped OP medications, and 23 % of subjects added or started a new OP medication
      during follow-up, with the first addition or start of a new OP medication
      occurring in a mean of 739 days after original OP treatment. INTRODUCTION: We
      described patterns and predictors of OP medication use, focusing on treatment
      changes over time. METHODS: We analyzed health and pharmacy insurance claims for
      a large cohort of low-income Medicare beneficiaries with a drug benefit for the
      years 1998-2008. Study subjects had documented Medicare claims and no receipt of
      OP medications (i.e., bisphosphonate, raloxifene, calcitonin, teriparatide, or
      hormonal therapy) during a baseline of 180 days. Subjects were then required to
      start an OP medication. Baseline patient and prescriber characteristics were
      assessed in multivariable Cox regression models to identify correlates of adding
      or starting a new OP medication. Fractures, bone mineral density testing, and
      visits with endocrinologists or rheumatologists occurring after baseline were
      also examined as correlates. RESULTS: We included 125,954 new users of OP
      medications with a mean age of 78 years, 97 % female, and 92 % white. OP
      medication prescribers included specialists (i.e., endocrinologists or
      rheumatologists) (6.2 %), orthopedic surgeons (1.0 %), primary care providers
      (64.9 %), other physicians (3.7 %), and missing (24.1 %). Seventy-seven percent
      of subjects stopped OP medications, and 23 % of subjects added or started a new
      OP medication during follow-up, with the first addition or start of a new OP
      medication occurring in a mean of 739 days after original OP treatment; 4 % added
      or started a new OP medication more than once. In fully adjusted models, many
      baseline variables correlated with starting a second OP medication. Post-baseline
      fractures [hazard ratio (HR) 1.76, 95 % confidence interval (CI) 1.71-1.82] and
      bone mineral density testing (HR 2.94, 95 % CI 2.86-3.03) were strong predictors.
      CONCLUSION: Approximately one quarter of patients starting an OP medication added
      or started a new OP medication during follow-up. Long-term sequential treatment
      strategy trials would inform optimal medication treatment for OP.

PMID- 24899107
TI  - Generalized phase behavior of cluster formation in colloidal dispersions with
      competing interactions.
AB  - Colloidal liquids interacting with short range attraction and long range
      repulsion, such as proposed for some protein solutions, have been found to
      exhibit novel states consisting of equilibrium particle clusters. Monte Carlo
      simulations are performed for two physically meaningful inter-particle potentials
      across a broad range of interaction parameters, temperatures and volume fractions
      to locate the conditions where clustered states are found. A corresponding states
      phase behavior is identified when normalized by the critical point of an
      appropriately selected reference attractive fluid. Clustered fluid states and
      cluster percolated states are found exclusively within the two phase region of
      the state diagram for a reference attractive fluid, confirming the underlying
      intrinsic relation between clustered states and bulk phase separation. Clustered
      and cluster percolated states consistently exhibit an intermediate range order
      peak in their structure factors with a magnitude above 2.7, leading to a semi
      empirical rule for identifying clustered fluids in scattering experiments. 

PMID- 24899108
TI  - The effect of heart failure nurse consultations on heart failure patients'
      illness beliefs, mood and quality of life over a six-month period.
AB  - AIMS AND OBJECTIVES: To explore the effect contact with a heart failure nurse can
      have on patients' illness beliefs, mood and quality of life. BACKGROUND: There is
      growing interest in patients' illness beliefs and the part they play in a
      patients understanding of chronic disease. DESIGN: Secondary analysis on two
      independent datasets. Patients were recruited from five UK hospitals, four in
      London and one in Sussex. Patients were recruited from an inpatient and
      outpatient setting. The first dataset recruited 174 patients with newly diagnosed
      heart failure, whilst the second dataset recruited 88 patients with an existing
      diagnosis of heart failure. METHODS: Patients completed the Minnesota Living with
      Heart Failure Questionnaire, Hospital Anxiety and Depression Scale, Illness
      Perception Questionnaire and the Treatment Representations Inventory at baseline
      and six months. We used a linear regression model to assess the association that
      contact with a heart failure nurse had on mood, illness beliefs and quality of
      life over a six-month period. RESULTS: Patients who had contact with a heart
      failure nurse were more satisfied with their treatment and more likely to believe
      that their heart failure was treatable. Contact with a heart failure nurse did
      not make a statistically significant difference to mood or quality of life.
      CONCLUSIONS: This study has shown that contact with a heart failure nurse can
      improve patient satisfaction with treatment decisions but has less influence on a
      patient's beliefs about their personal control, treatment control and treatment
      concerns. With appropriate support, skills and training, heart failure nurses
      could play an important role in addressing individual patient's beliefs. There is
      a need to further investigate this. RELEVANCE TO CLINICAL PRACTICE: Exploring
      patients' illness beliefs and mood could help to enhance person-centred care.
      Heart failure nurses would need additional training in the techniques used.

PMID- 24899109
TI  - Confidence limits, error bars and method comparison in molecular modeling. Part
      1: the calculation of confidence intervals.
AB  - Computational chemistry is a largely empirical field that makes predictions with
      substantial uncertainty. And yet the use of standard statistical methods to
      quantify this uncertainty is often absent from published reports. This article
      covers the basics of confidence interval estimation for molecular modeling using
      classical statistics. Alternate approaches such as non-parametric statistics and
      bootstrapping are discussed. 

PMID- 24899112
TI  - Silavinylidene stabilized by an N-heterocyclic carbene: a theoretically predicted
      stable molecule.
AB  - Quantum chemical calculations show that the N-heterocyclic carbene (NHC)
      stabilized silavinylidene, NHC(tBu)->C=SiR2 is a strongly bonded complex, which
      has a linear arrangement of the donor and acceptor moieties. The molecule is the
      energetically lowest lying isomer of the NHC-stabilized R2CSi isomers and it is
      stable towards dimerization when R is a bulky substituent. The silavinylidene
      complex is the only species of the silylidene homologues NHC(tBu)->E=E'R2 (E, E'
      = C-Pb) which possesses a linear arrangement. The unusual bonding situation is
      explained in terms of donor-acceptor interactions between NHC(tBu) as sigma donor
      and C=SiR2 in the doubly excited singlet state 3a1=>2b2 which leads to a
      significantly shorter C-SiR2 bond compared with free C=SiR2 .

PMID- 24899110
TI  - Ligand efficiency metrics considered harmful.
AB  - Ligand efficiency metrics are used in drug discovery to normalize biological
      activity or affinity with respect to physicochemical properties such as
      lipophilicity and molecular size. This Perspective provides an overview of ligand
      efficiency metrics and summarizes thermodynamics of protein-ligand binding.
      Different classes of ligand efficiency metric are critically examined and the
      study concludes with suggestions for alternative ways to account for
      physicochemical properties when prioritizing and optimizing leads. 

PMID- 24899111
TI  - Annual decline in estimated glomerular filtration rate is a risk factor for
      cardiovascular events independent of proteinuria.
AB  - AIMS: Chronic kidney disease is a risk factor of the development of
      cardiovascular disease (CVD). However, it is not clear whether decline of
      glomerular filtration rate (GFR), not reduced GFR, is a risk factor for the
      incidence of CVD independent of proteinuria. METHODS: By using a population-based
      521 123 person-years longitudinal cohort receiving annual health checkups from
      2008 to 2010, we examined whether the annual decline of estimated GFR is a risk
      factor for CVD development independent of proteinuria. RESULTS: During the follow
      up period, there were 12 041 newly developed CVD events, comprising 4426 stroke
      events and/or 8298 cardiac events. As expected, both reduced estimated GFR and
      proteinuria were risk factors for the development of CVD in our study population.
      Moreover, annual decline of estimated GFR was a significant and independent risk
      factor for the incidence of CVD (HR [95% CI], 1.23 [1.18-1.28] in males or 1.14
      [1.10-1.18] in females for -10% per year) with covariant adjustment for
      proteinuria and reduced estimated GFR. CONCLUSION: Annual decline of GFR is an
      independent risk factor for CVD. Serial measurement of both creatinine and
      proteinuria would be better to predict the incidence of CVD in the general
      population.

PMID- 24899113
TI  - Milrinone via lumbar subarachnoid catheter for vasospasm after aneurysmal
      subarachnoid hemorrhage.
AB  - INTRODUCTION: Delayed ischemic neurological deficit (DIND) due to symptomatic
      vasospasm is a major cause of morbidity and mortality after aneurysmal
      subarachnoid hemorrhage (aSAH). The aim of this study was to elucidate the safety
      and feasibility of intrathecal milrinone infusion via lumber subarachnoid
      catheter for prevention of DIND after aSAH. METHODS: We diagnosed 425 consecutive
      patients with aSAH who received clipping or coil embolization within 48 h after
      arrival. Patients with the evidence of vasospasm on CT angiography (CTA) received
      the milrinone therapy via lumbar subarachnoid catheter. DIND, delayed cerebral
      infarction (DCI), and modified Rankin scale at 3 months after SAH were used for
      the assessment of outcome. RESULTS: Of 425 patients, 170 patients (40.0 %) with
      CTA-proven vasospasm received the milrinone therapy. DIND was observed in 68
      patients (16.0 %), DCI in 30 patients (7.1 %), and the overall mortality was 7.2
      %. In patients with WFNS grade IV and V aSAH, 26 out of 145 patients (17.9 %)
      were presented with DIND, 12 (8.3 %) with DCI, and the mortality was 16.0 %. No
      major complication related to the milrinone injection was observed. CONCLUSION:
      Intrathecal milrinone injection via lumbar catheter was safe and feasible, and
      further randomized prospective studies are needed to confirm the effectiveness of
      this regimen in the patients with SAH.

PMID- 24899114
TI  - Population management of rock hyraxes (Procavia capensis) in residential areas.
AB  - BACKGROUND: Frequent reports of rock hyrax (Procavia capensis) invasions in
      residential areas prompted an investigation of this problem in order to identify
      possible solutions. From these reports, problem areas in South Africa were
      identified, and sites within the Free State Province were selected for this
      study. At these sites, rock hyrax populations demonstrate an unusual annual
      increase. This increase has led to a food and habitat shortage, forcing
      individuals into residential areas in search of additional refuges and food
      sources. In order to manage populations, several preventive as well as control
      methods have been assessed and implemented. Population densities were determined
      using the Lincoln index and the Robson-Whitlock technique. Wild populations were
      included in the study for comparison purposes. RESULTS: Additional resources
      within residential areas have facilitated populations to grow much larger, in
      some instances exceeding the natural limits (30-40 individuals) by 470%. This
      influx contributes to human-wildlife conflict. With the use of relocation,
      populations were reduced within 3 months. DISCUSSION: Preventive methods have
      shown various levels of success. Specific combinations of these methods have
      proved to be more effective than others. The strategy of capture and relocation
      of individuals for rapid reduction in the population has been successful.
      Preliminary results show that the establishment of relocated populations is not
      successful owing to high predation rates. The reintroduction of natural predators
      for rock hyrax population control appears to have positive results, but this will
      have to be monitored on a regular basis.

PMID- 24899115
TI  - The impact of biopreservatives and storage temperature in the quality and safety
      of minimally processed mixed vegetables for soup.
AB  - BACKGROUND: The combined effects of bioactive agents (tea tree essential oil,
      propolis extract and gallic acid) and storage temperature on the microbiological
      and sensory quality of fresh-cut mixed vegetables for soup (celery, leek and
      butternut squash) were studied with the objective of preserving its quality and
      safety. RESULTS: Refrigeration temperature was confirmed as the main factor to
      limit the growth of spoilage and pathogenic microorganisms. Biopreservatives
      applied on mixed vegetables were effective only when combined with optimal
      refrigeration temperature (5  degrees C). Bioactive compounds showed slight
      effectiveness in controlling the microbiota present in mixed vegetables, although
      coliforms were greatly reduced by gallic acid and propolis treatments, achieving
      0.5-2 log unit reductions during storage. Also, these agents showed antimicrobial
      activity against endogenous Escherichia coli and inoculated E. coli O157:H7,
      exerting a bacteriostatic effect and reducing population counts by 0.9-1.2 log
      CFU g(-1) at 10 days of refrigerated storage. The combination of propolis
      treatment with refrigerated storage conditions effectively preserved the sensory
      quality and prolonged the sensory shelf life of fresh-cut mixed vegetables by 3
      days. CONCLUSION: The use of natural agents such as propolis extract to preserve
      the quality and safety of mixed vegetables for soup might be an interesting
      option to address the concerns of the consumer about the use of synthetic
      chemical antimicrobials potentially harmful to health.

PMID- 24899116
TI  - An investigation into the MMP1 gene promoter region polymorphism--1607 2G with
      recessive dystrophic epidermolysis bullosa disease severity in northeastern
      Mexican patients.
AB  - BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic
      skin blistering disorder caused by mutations in the gene COL7A1 encoding type VII
      collagen. Most of the patients' clinical severity depends in part on the nature
      and location of the mutations, ranging from the mild form described as RDEBother
      generalized (RDEB-O) to the more aggressive phenotype described as RDEBsevere
      generalized (RDEB-sev gen). However, interfamilial and interindividual
      differences in subjects with identical COL7A1 mutations suggest the presence of
      modifier elements, which may influence severity. There is a single nucleotide
      polymorphism (SNP) at the promoter of the MMP1 gene-encoding matrix
      metalloproteinase type 1, which has been studied as a genetic disease modifier in
      different patient cohorts with different findings. METHODS: We tested the SNP in
      30 patients with RDEB and 130 controls whose four grandparents were born in
      northeastern Mexico. Patients were clinically classified as RDEB-sev gen and RDEB
      O by three dermatologists. The SNPStats, RXC, and SPSS software were used to
      perform statistical testing. RESULTS: The allele frequencies for 2G were 0.607,
      0.562, and 0.642 for RDEB-O, RDEB-sev gen, and the control group, respectively.
      When the genotype frequencies were compared, there was no significant difference
      between RDEB-sev gen (OR = 0.38, CI 95% 0.12-1.21), RDEB-O (OR = 1.03, CI 95%
      0.21-4.96), and the control group. CONCLUSION: We found no significant
      association in relation to the severity of the study subjects and the SNP at the
      promoter of the MMP1 gene.

PMID- 24899117
TI  - Attentional capture by signals of threat.
AB  - Attention can be captured automatically by events that are physically salient.
      Similarly, emotional stimuli are known to be prioritised by the visual system
      because of their behavioural significance. The present study investigated whether
      a neutral stimulus which became associated with fear captured attention in visual
      search. Using a fear-conditioning procedure, one stimulus was repeatedly combined
      with an electrical shock (CS+), whereas another stimulus with identical physical
      features was never combined with a shock (CS-). Following conditioning,
      participants had to search for a target; while on some trials, either an
      irrelevant CS+ or CS- stimulus was present. The results show that the presence of
      an irrelevant distractor that was previously associated with fear slowed a search
      more than a distractor without fear association. The current results indicate
      that learned fear associations have the ability to capture our attention even if
      we try to ignore them. 

PMID- 24899118
TI  - A reliable aerosol-spray-assisted approach to produce and optimize amorphous
      metal oxide catalysts for electrochemical water splitting.
AB  - An aerosol-spray-assisted approach (ASAA) is proposed and confirmed as a
      precisely controllable and continuous method to fabricate amorphous mixed metal
      oxides for electrochemical water splitting. The proportion of metal elements can
      be accurately controlled to within (5+/-5) %. The products can be sustainably
      obtained, which is highly suitable for industrial applications. ASAA was used to
      show that Fe6Ni10O(x) is the best catalyst among the investigated Fe-Ni-O(x)
      series with an overpotential of as low as 0.286 V (10 mA cm(-2)) and a Tafel
      slope of 48 mV/decade for the electrochemical oxygen evolution reaction.
      Therefore, this work contributes a versatile, continuous, and reliable way to
      produce and optimize amorphous metal oxide catalysts.

PMID- 24899119
TI  - Using data from patient interactions in primary care for population level chronic
      disease surveillance: The Sentinel Practices Data Sourcing (SPDS) project.
AB  - BACKGROUND: Population health planning within a health district requires current
      information on health profiles of the target population. Information obtained
      during primary care interactions may provide a valuable surveillance system for
      chronic disease burden. The Sentinel Practices Data Sourcing project aimed to
      establish a sentinel site surveillance system to obtain a region-specific
      estimate of the prevalence of chronic diseases and mental health disorders within
      the Illawarra-Shoalhaven region of New South Wales, Australia. METHODS: In
      September 2013, de-identified information for all patient interactions within the
      preceding 24 months was extracted and collated using a computerised chronic
      disease management program that has been designed for desktop application (Pen
      Computer Systems Clinical Audit Tool: TM (PCS CAT)). Collated patient data
      included information on all diagnosed pathologies and mental health indicators,
      clinical variables such as anthropometric measures, and patient demographic
      variables such as age, sex, geographical location of residence and indigenous
      status. Age-standardised prevalence of selected health conditions was calculated.
      RESULTS: Of the 52 general practices within the 6 major Statistical Local Areas
      (SLAs) of the health district that met the inclusion criteria, 17 consented to
      participate in the study, yielding data on n = 152,767 patients, and representing
      39.7% of the regional population. Higher than national average estimates were
      found for the age-adjusted prevalence of chronic diseases such as
      obesity/overweight (65.9% vs 63.4%), hypertension (11.9% vs 10.4%) and anxiety
      disorders (5.0% vs 3.8%), but a lower than national average age-adjusted
      prevalence of asthma (8.0% vs 10.2%) was also identified. CONCLUSIONS: This proof
      of-concept study has demonstrated that the scope of data collected during patient
      visits to their general practitioners (GPs), facilitated through the Medicare
      funded primary health care system in Australia, provides an opportunity for
      monitoring of chronic disease prevalence and its associated risk factors at the
      local level. Selection of sentinel sites that are representative of the
      population being served will facilitate an accurate and region-specific system
      for the purpose of population health planning at the primary care level.

PMID- 24899120
TI  - The provision of assistive devices and home adaptations to patients with ALS in
      the Netherlands: patients' perspectives.
AB  - The timely provision of assistive devices and home adaptations (ADHA) is crucial
      in the management of patients with amyotrophic lateral sclerosis (ALS) in order
      to maintain their independence and relieve their caregivers. Our objective was to
      study the experiences of patients with ALS during the process of procuring ADHA.
      We sent a cross-sectional questionnaire survey addressing issues concerning the
      application for and provision process of ADHA to 239 patients with ALS registered
      at one of the three tertiary academic diagnostic centres within the Netherlands
      ALS Centre. One hundred and fifty-nine (89%) of the 179 responding patients
      (response rate 75%) had experience with the procurement process and 93 (58%) of
      them indicated problems in obtaining ADHA. The most reported problems were delay
      (42%) and the authorities' lack of disease knowledge (24%). Patients viewed these
      issues as the most prominent requiring improvement. In conclusion, the main
      problems perceived by patients indicate that increasing awareness of ALS and
      promoting a proactive attitude among ALS care professionals towards the
      application for ADHA may contribute positively to the quality of ALS care.

PMID- 24899121
TI  - A trinuclear Zn3(OAc)4-3,3'-bis(aminoimino)binaphthoxide complex for highly
      efficient catalytic asymmetric iodolactonization.
AB  - A 3,3'-bis(aminoimino)BINOL ligand was newly designed and synthesized for the
      formation of a trinuclear Zn complex upon reaction with Zn(OAc)2. Using the
      harmony of the tri-zinc atoms, 1 mol% Zn3(OAc)4-3,3'-bis(aminoimino)binaphthoxide
      catalyzed asymmetric iodolactonization in up to 99.9% ee. 

PMID- 24899122
TI  - SIX1 gene: absence of mutations in children with isolated congenital anomalies of
      kidney and urinary tract.
AB  - BACKGROUND: Mutations in human SIX1 gene cause branchiootorenal or branchiootic
      syndrome. Six1 deficient mice exhibit uni- or bilateral renal hypoplasia or
      kidney agenesis. Furthermore a lack of Six1 gene in the ureter leads to
      hydroureter and hydronephrosis. These murine malformations resemble human kidney
      and urinary tract congenital anomalies (CAKUT), a group of diseases with a
      diverse anatomical spectrum which includes duplex collecting system as much as
      urethra kidney and ureteropelvic anomalies. Our study focuses on whether
      mutations or deletion of this gene may be associated with nonsyndromic CAKUT.
      METHODS: Fifty unrelated patients (13-21 years) with nonsyndromic CAKUT were
      retrospectively recruited for SIX1 sequence variations analysis, and compared to
      three subjects without malformative nephrouropathies (controls). SIX1 coding
      sequence was screened by high resolution melt analysis (HRMA) and by Sanger
      direct sequencing. A quantitative comparative real-time polymerase chain reaction
      (PCR) was later performed in order to detect the presence of SIX1 gene deletion.
      RESULTS: We did not find significant differences in the HRMA melting curves for
      each of the SIX1 coding exons between patients and controls, as also confirmed by
      Sanger direct sequencing. Moreover quantitative comparative real-time PCR for
      SIX1 and data normalization excluded total SIX1 gene deletion in our patients.
      CONCLUSIONS: We did not find sequence variations in SIX1 coding regions or
      complete gene deletion in our CAKUT population. These results suggest that
      alterations in these sequences are unlikely to be a major cause of nonsyndromic
      CAKUT. Nevertheless, further studies are necessary to understand if altered SIX1
      expression may play a role in human development of kidney and urinary tract
      congenital anomalies.

PMID- 24899123
TI  - Urine interleukin-18 in prediction of acute kidney injury: a systemic review and
      meta-analysis.
AB  - BACKGROUND: Interleukin-18 (IL-18) mediates ischemic acute tubular necrosis; it
      has been proved as a rapid, reliable, and affordable test marker for the early
      detection of acute kidney injury (AKI), but its predictive accuracy varies
      greatly. METHODS: MEDLINE and EMBASE, Cochrane Library, Ovid, and Springerlink
      (from inception to November 15, 2013) were searched for relevant studies (in
      English) investigating diagnostic accuracy of urine IL-18 to predict AKI in
      various clinical settings. The text index was increasing or increased urine IL-18
      level and the main outcome was the development of AKI, which was primarily based
      on serum creatinine level [using risk, injury, failure, loss and end-stage renal
      disease (RIFLE), acute kidney injury network, or modified pediatric RIFLE
      criteria in pediatric patients]. Pooled estimates of diagnostic odds ratio (OR),
      sensitivity and specificity were calculated. Summary receiver operating
      characteristic curves were used to calculate the measures of accuracy and Q point
      value (Q*). Remarkable heterogeneity was explored further by subgroup analysis
      based on the different clinical settings. RESULTS: We analyzed data from 11
      studies of 3 countries covering 2,796 patients. These studies were marked by
      limitations of threshold and non-threshold effect heterogeneity. Across all
      settings, the diagnostic OR for urine IL-18 level to predict AKI was 5.11 [95%
      confidence interval (CI) 3.22-8.12], with sensitivity and specificity
      respectively at 0.51 and 0.79. The area under the ROC curve of urine IL-18 level
      to predict AKI was 0.77 (95% CI 0.71-0.83). Subgroup analysis showed that urine
      IL-18 level in pediatric patients (<18 years) and early AKI predictive time (<12
      h) were more effective in predicting AKI, with diagnostic ORs of 7.51 (2.99
      18.88), 8.18 (2.19-30.51), respectively. CONCLUSION: Urine IL-18 holds promise as
      a biomarker in the prediction of AKI but has only moderate diagnostic value.

PMID- 24899125
TI  - Longitudinal changes in objectively measured sedentary behaviour and their
      relationship with adiposity in children and adolescents: systematic review and
      evidence appraisal.
AB  - This review aimed to determine longitudinal changes in objectively measured
      overall sedentary behaviour, and to examine their associations with adiposity in
      children and adolescents. A search for longitudinal studies was performed using
      several electronic databases. Of 161 potentially eligible papers, 10 for change
      in sedentary behaviour and 3 for longitudinal associations with change in
      adiposity were included. Weighted mean increase in daily sedentary behaviour per
      year was 5.7% for boys and 5.8% for girls. Only one paper included preschool
      children, and it showed a decrease in sedentary behaviour. Nine studies were from
      Western countries. Null associations were reported between sedentary behaviour
      and adiposity in two studies, the other found that increases in sedentary
      behaviour were associated with increases in adiposity, but only in those with
      body mass index above the 50th percentile. There was consistent evidence that
      sedentary behaviour increases with age in school-age children and adolescents, by
      approximately 30 min extra daily sedentary behaviour per year. There was little
      evidence on the influence of changes in sedentary behaviour on changes in
      adiposity. There is a need for more longitudinal research, for more evidence from
      outside the Western world, and for more studies that examine 'dose-response'
      associations between changes in sedentary behaviour and changes in adiposity. 

PMID- 24899124
TI  - Associations of dietary macronutrients with glomerular filtration rate and kidney
      dysfunction: Tehran lipid and glucose study.
AB  - BACKGROUND: Although dietary components may play a role in the development of
      chronic kidney disease (CKD), data on this topic are scarce. The objective of
      this study was to investigate the association between macronutrient intakes and
      CKD in a large non-diabetic adult population-based study. METHODS: This cross
      sectional study recruited 5,316 participants aged >=27 years without diabetes
      within the framework of the Tehran lipid and glucose study. Dietary intake was
      collected using a validated food-frequency questionnaire. Macronutrients intake
      including total-, animal-, and plant-protein, carbohydrate, simple sugar,
      fructose, total fat, saturated fatty acids, poly- and monounsaturated-fatty acids
      (PUFA and MUFA), and n-3 and n-6 fatty acids was categorized into quartiles.
      Anthropometrics, blood pressure, serum creatinine, and fasting plasma glucose and
      lipids were measured. Estimated glomerular filtration rate (eGFR) was calculated
      using the Modification of Diet in Renal Disease Study equation. CKD was defined
      as eGFR <60 ml/min/1.73 m(2). RESULT: Mean age of participants was 45.0 +/- 12.2
      years. Mean eGFR was 71.9 +/- 11.1 ml/min/1.73 m(2), and 13% had CKD. After
      adjustment for serum triglycerides and cholesterol, body mass index, and
      hypertension, the risk of CKD decreased in the highest quartile compared to
      lowest quartile of plant protein (OR, 95% CI) (0.70, 0.51-0.97), PUFA (0.73, 0.55
      0.99), and n-6 fatty acids (0.75, 0.57-0.97). However, the risk of CKD increased
      in the highest quartile of animal protein (1.37, 1.05-1.79) compared to the
      lowest. CONCLUSION: Plant protein, PUFA, and n-6 fatty acids are associated with
      a lower risk of CKD, independently of hypertension and diabetic mellitus, while
      animal protein may be a risk factor for CKD in adults.

PMID- 24899126
TI  - Identification of genes required for the survival of B. fragilis using massive
      parallel sequencing of a saturated transposon mutant library.
AB  - BACKGROUND: Bacteroides fragilis is a Gram-negative anaerobe that is normally a
      human gut commensal; it comprises a small percentage of the gut Bacteroides but
      is the most frequently isolated Bacteroides from human infections. Identification
      of the essential genes necessary for the survival of B. fragilis provides novel
      information which can be exploited for the treatment of bacterial infections.
      RESULTS: Massive parallel sequencing of saturated transposon mutant libraries
      (two mutant pools of approximately 50,000 mutants each) was used to determine the
      essential genes for the growth of B. fragilis 638R on nutrient rich medium. Among
      the 4326 protein coding genes, 550 genes (12.7%) were found to be essential for
      the survival of B. fragilis 638R. Of the 550 essential genes, only 367 genes were
      assigned to a Cluster of Orthologous Genes, and about 290 genes had Kyoto
      Encyclopedia of Genes and Genomes orthologous members. Interestingly, genes with
      hypothetical functions accounted for 41.3% of essential genes (227 genes),
      indicating that the functions of a significant percentage of the genes used by B.
      fragilis 638R are still unknown. Global transcriptome analysis using RNA-Seq
      indicated that most of the essential genes (92%) are, in fact, transcribed in B.
      fragilis 638R including most of those coding for hypothetical proteins. Three
      hundred fifty of the 550 essential genes of B. fragilis 638R are present in
      Database of Essential Genes. 10.02 and 31% of those are genes included as
      essential genes for nine species (including Gram-positive pathogenic bacteria).
      CONCLUSIONS: The essential gene data described in this investigation provides a
      valuable resource to study gene function and pathways involved in B. fragilis
      survival. Thorough examination of the B. fragilis-specific essential genes and
      genes that are shared between divergent organisms opens new research avenues that
      will lead to enhanced understanding of survival strategies used by bacteria in
      different microniches and under different stress situations.

PMID- 24899127
TI  - Functional characterization of the S41Y (C2755A) polymorphism of tryptophan
      hydroxylase 2.
AB  - Human TPH2 (hTPH2) catalyzes the rate-limiting step in CNS serotonin
      biosynthesis. We characterized a single-nucleotide polymorphism (C2755A) in the
      hTPH2 gene that substitutes tyrosine for serine at position 41 in the regulatory
      domain of the enzyme. This polymorphism is associated with bipolar disorder and
      peripartum depression in a Chinese population. Recombinant h TPH2 human proteins
      were expressed in bacteria and also stably expressed in PC12 cells. Following
      bacterial expression and purification, the tyrosine for serine substitution at
      position 41 (S41Y) polymorphic enzyme displayed increased Vmax with unchanged Km
      values. By contrast, enzyme stability was decreased in vitro from 32 min to 4 min
      (37  degrees C) for the S41Y enzyme (as compared to the wild-type enzyme). The
      S41Y polymorphism decreased cyclic AMP-dependent protein kinase A-mediated
      phosphorylation ~ 50% relative to wild-type hTPH2, suggesting that the S41Y
      mutation may disrupt the post-translational regulation of this enzyme.
      Transfected PC12 cells expressed hTPH2 mRNA, active protein, and synthesized and
      released serotonin. Paradoxically, while S41Y-transfected PC12 cells expressed
      higher levels of hTPH2 than wild type, they synthesized less serotonin. These
      findings suggest a modified regulation of the S41Y gene variant leading to
      altered regulation and reduced neurotransmitter synthesis that may contribute to
      association of the polymorphism with bipolar disorder and depression. We report
      the functional implications of a polymorphic human tryptophan hydroxylase-2 gene
      associated with depression and bipolar disorder. The polymorphic enzyme (serine
      41 converted to tyrosine) has increased activity, but decreased enzyme stability
      and serotonin production. Moreover, cyclic AMP-dependent protein kinase (PKA)
      mediated phosphorylation of the mutant enzyme is decreased suggesting modified
      regulation of the S41Y variant leading to altered serotonin.

PMID- 24899129
TI  - Valproic acid, an anti-epileptic drug and a histone deacetylase inhibitor, in
      combination with proteasome inhibitors exerts antiproliferative, pro-apoptotic
      and chemosensitizing effects in human colorectal cancer cells: underlying
      molecular mechanisms.
AB  - Although the therapeutic efficacy of valproic acid (VPA) has been observed in
      patients with solid tumors, the very high concentration required to induce
      antitumor activity limits its clinical utility. The present study focused on the
      development of combined molecular targeted therapies using VPA and proteasome
      inhibitors (PIs: MG132, PI-1 and PR-39) to determine whether this combination of
      treatments has synergistic anticancer and chemosensitizing effects against
      colorectal cancer. Furthermore, the potential molecular mechanisms of action of
      the VPA/PI combinations were evaluated. The effects of VPA in combination with
      PIs on the growth of colorectal cancer cells were assessed with regard to
      proliferation, cell cycle, apoptosis, reactive oxygen species (ROS) generation
      and the expression of genes that control the cell cycle, apoptosis and pro
      survival/stress-related pathways. Treatment with combinations of VPA and PIs
      resulted in an additive/synergistic decrease in colorectal cancer cell
      proliferation compared to treatment with VPA or PIs alone. The combination
      treatment was associated with a synergistic increase in apoptosis and in the
      number of cells arrested in the S phase of the cell cycle. These events were
      associated with increased ROS generation, pro-apoptotic gene expression and
      stress-related gene expression. These events were also associated with the
      decreased expression of anti-apoptotic genes and pro-survival genes. The
      combination of VPA with MG132 or PI-1 enhanced the chemosensitivity of the SW1116
      (29-185-fold) and SW837 (50-620-fold) colorectal cancer cells. By contrast, the
      combination of VPA/PR-39 induced a pronounced increase in the chemosensitivity of
      the SW837 (16-54-fold) colorectal cancer cells. These data provide a rational
      basis for the clinical use of this combination therapy for the treatment of
      colorectal cancer.

PMID- 24899128
TI  - Modifiable and non-modifiable risk factors for poor sperm morphology.
AB  - STUDY QUESTION: Are common lifestyle factors associated with poor sperm
      morphology? SUMMARY ANSWER: Common lifestyle choices make little contribution to
      the risk of poor sperm morphology. WHAT IS KNOWN ALREADY: Although many studies
      have claimed that men's lifestyle can affect sperm morphology, the evidence is
      weak with studies often underpowered and poorly controlled. STUDY DESIGN, SIZE,
      DURATION: Unmatched case-referent study with 318 cases and 1652 referents. Cases
      had poor sperm morphology (<4% normal forms based on 200 sperm assessed).
      Exposures included self-reported exposures to alcohol, tobacco, recreational
      drugs as well as occupational and other factors. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Eligible men, aged 18 years or above, were part of a couple who had been
      attempting conception without success following at least 12 months of unprotected
      intercourse and also had no knowledge of any semen analysis before being
      enrolled. They were recruited from 14 fertility clinics across the UK during a 37
      month period from 1 January 1999. MAIN RESULTS AND THE ROLE OF CHANCE: Risk
      factors for poor sperm morphology, after adjustment for centre and other risk
      factors, included: (i) sample production in summer [odds ratio (OR) = 1.99, 95%
      confidence interval (CI) 1.43-2.72]; and (ii) use of cannabis in the 3 months
      prior to sample collection in men aged <=30 years (OR = 1.94, 95% CI 1.05-3.60).
      Men who produced a sample after 6 days abstinence were less likely to be a case
      (OR = 0.64, 95% CI 0.43-0.95). No significant association was found with body
      mass index, type of underwear, smoking or alcohol consumption or having a history
      of mumps. This suggests that an individual's lifestyle has very little impact on
      sperm morphology and that delaying assisted conception to make changes to
      lifestyle is unlikely to enhance conception. LIMITATIONS, REASONS FOR CAUTION:
      Data were collected blind to outcome and so exposure information should not have
      been subject to reporting bias. Less than half the men attending the various
      clinics met the study eligibility criteria and among those who did, two out of
      five did not participate. It is not known whether any of those who refused to
      take part did so because they had a lifestyle which they did not want subjected
      to investigation. Although the power of the study was sufficient to draw
      conclusions about common lifestyle choices, this is not the case for exposures
      that were rare or poorly reported. WIDER IMPLICATIONS OF THE FINDINGS: All
      participating clinics saw patients at no cost (under the UK National Health
      Service) and the study population may differ from those in countries without such
      provision. Even within the UK, low-income couples may choose not to undertake any
      investigation believing that they would subsequently be unable to afford
      treatment. Since a computer performed the measurements of sperm morphology, these
      results may not be comparable with studies where sperm morphology was assessed by
      other methods. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the UK
      Health and Safety Executive, the UK Department of Environment, Transport and the
      Regions, the UK Department of Health (Grant Code DoH 1216760) and the European
      Chemical Industry Council (grant code EMSG19). No competing interests declared.

PMID- 24899131
TI  - Ecological drivers of guanaco recruitment: variable carrying capacity and density
      dependence.
AB  - Ungulates living in predator-free reserves offer the opportunity to study the
      influence of food limitation on population dynamics without the potentially
      confounding effects of top-down regulation or livestock competition. We assessed
      the influence of relative forage availability and population density on guanaco
      recruitment in two predator-free reserves in eastern Patagonia, with contrasting
      scenarios of population density. We also explored the relative contribution of
      the observed recruitment to population growth using a deterministic linear model
      to test the assumption that the studied populations were closed units. The
      observed densities increased twice as fast as our theoretical populations,
      indicating that marked immigration has taken place during the recovery phase
      experienced by both populations, thus we rejected the closed-population
      assumption. Regarding the factors driving variation in recruitment, in the low-
      to medium-density setting, we found a positive linear relationship between
      recruitment and surrogates of annual primary production, whereas no density
      dependence was detected. In contrast, in the high-density scenario, both annual
      primary production and population density showed marked effects, indicating a
      positive relationship between recruitment and per capita food availability above
      a food-limitation threshold. Our results support the idea that environmental
      carrying capacity fluctuates in response to climatic variation, and that these
      fluctuations have relevant consequences for herbivore dynamics, such as
      amplifying density dependence in drier years. We conclude that including the
      coupling between environmental variability in resources and density dependence is
      crucial to model ungulate population dynamics; to overlook temporal changes in
      carrying capacity may even mask density dependence as well as other important
      processes. 

PMID- 24899130
TI  - A new, bioactive, antibacterial-eluting, composite graft for infection-free wound
      healing.
AB  - The current work focuses on the in vivo performance of a newly developed
      injectable composite graft in infected full-thickness wounds. The composite graft
      was composed of bioactive porous Poly dl-lactide-co-glycolide scaffolds,
      antibiotic gentamicin, and crosslinked gelatin as carrier gel. Treated infected
      wounds exhibited a faster wound closure, rapid weight gain, lower neutrophil
      count, higher breaking strength, and 100 times lesser microbial count (10(2)
      colony forming units/g in infected treated vs. 10(4)  colony forming units/g in
      infected control group) in comparison with infected control group 28 days post
      treatment. During healing, collagen production was more in the treated groups at
      day 7 than controls and thereafter gradually reduced to normal levels. Histology
      revealed a mature scar tissue formation, fibroblast proliferation, epidermal
      resurfacing, and collagen deposition in reticular alignment similar to normal
      healthy skin in treated wounds. Further, the plasma concentration of gentamicin
      was 35-45 MUg/mL during the initial 12 hours and reduced to 1 MUg/mL in 24 hours,
      which indicated safe levels of the antibiotic drug during healing. These results
      clearly indicate a faster, infection-free, and safe after treatment with the
      developed graft.

PMID- 24899133
TI  - Multiphase optofluidics on an electro-microfluidic platform powered by
      electrowetting and dielectrophoresis.
AB  - For diverse material phases used on an electro-microfluidic (EMF) platform,
      exploiting the electro-optical properties of matter in varied phases is essential
      to reap the benefits of the optofluidic capabilities of that platform. Materials
      in the four fundamental phases--solid-phase dielectric layer, liquid-phase
      droplet, gas-phase bubble, and plasma-phase bubble microplasma--have been
      investigated to offer electrically tunable optical characteristics for the
      manipulation of fluids on an EMF platform. Here we present an overview of the
      basic driving mechanisms for electrowetting and dielectrophoresis on the EMF
      platform. Three optofluidic examples occurring in multiple phases are described:
      solid optofluidics--liquid and light regulation by electrowetting on a solid
      polymer dispersed liquid crystal (PDLC) dielectric layer; liquid optofluidics-
      transmittance and reflectance modulation with formation of particle chains in a
      liquid droplet; and gas and plasma optofluidics--ignition and manipulation of a
      bubble microplasma by liquid dielectrophoresis. By combining the various
      materials possessing diverse electro-optical characteristics in separate phases,
      the EMF platform becomes an ideal platform for integrated optofluidics.

PMID- 24899132
TI  - The importance of developing modeling frameworks to inform conservation
      decisions: a response to Lonergan.

PMID- 24899135
TI  - Long-term results of open stent-grafting using a Matsui-Kitamura stent to treat
      thoracic aortic aneurysm.
AB  - PURPOSE: We describe a retrospective study of initial and long-term outcomes with
      an open stent grafting (OSG) with a Matsui-Kitamura stent for treating thoracic
      aortic aneurysm. METHODS: Between August 2005 and September 2013, 50 patients
      with aortic arch disease extending to the descending aorta underwent OSG.
      Circulatory arrest with total cardiopulmonary bypass and selective cerebral
      perfusion were used, and the aorta was transected between the brachiocephalic and
      left subclavian artery. The stent-graft was inserted, sutured to a transected
      aortic edge, and anastomosed to a four-branched arch graft. Preoperative,
      operative, and short- and long-term postoperative data were obtained from the
      patients' medical records. RESULTS: The perioperative (within 30 days) mortality
      rate was 8%. Two patients (4%) had a stroke and 5 patients (10%) had a spinal
      cord injury resulting in paraplegia or paraparesis (1 patient each) or transient
      paraplegia (3 patients). Actuarial survival rates at 1, 3, 5, and 7 years
      postoperatively were 87.8%, 78.3%, 70.7%, and 65.3%, respectively; the rates of
      freedom from an aortic event were 100%, 89.1%, 82.2%, and 74.7%. There were no
      complications related to use of the stent-graft. CONCLUSION: Our OSG method
      provided durable results in patients treated for thoracic aortic aneurysm, with
      few adverse events.

PMID- 24899134
TI  - Aneuploidy in pluripotent stem cells and implications for cancerous
      transformation.
AB  - Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have
      emerged as a promising cell source for regenerative medicine, disease modeling
      and drug discovery. Assurance of genetic stability over long term maintenance of
      hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by
      acquiring non-random genetic changes that render them more robust and easier to
      grow. In separate studies between 12.5% and 34% of hPSC lines were found to
      acquire chromosome abnormalities over time, with the incidence increasing with
      passage number. The predominant genetic changes found in hPSC lines involve
      changes in chromosome number and structure (particularly of chromosomes 1, 12, 17
      and 20), reminiscent of the changes observed in cancer cells. In this review, we
      summarize current knowledge on the causes and consequences of aneuploidy in hPSCs
      and highlight the potential links with genetic changes observed in human cancers
      and early embryos. We point to the need for comprehensive characterization of
      mechanisms underpinning both the acquisition of chromosomal abnormalities and
      selection pressures, which allow mutations to persist in hPSC cultures.
      Elucidation of these mechanisms will help to design culture conditions that
      minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may
      provide a unique platform to analyse the driving forces behind the genome
      evolution that may eventually lead to cancerous transformation. 

PMID- 24899136
TI  - Imaging Characteristics in ALK Fusion-Positive Lung Adenocarcinomas by Using
      HRCT.
AB  - OBJECTIVES: We aimed to identify high-resolution computed tomography (HRCT)
      features useful to distinguish the anaplastic lymphoma kinase gene (ALK) fusion
      positive and negative lung adenocarcinomas. METHODS: We included 236 surgically
      resected adenocarcinoma lesions, which included 27 consecutive ALK fusion
      positive (AP) lesions, 115 epidermal growth factor receptor mutation-positive
      lesions, and 94 double-negative lesions. HRCT parameters including size, air
      bronchograms, pleural indentation, spiculation, and tumor disappearance rate
      (TDR) were compared. In addition, prevalence of small lesions (<=20 mm) and solid
      lesions (TDR <=20%) were compared. RESULTS: AP lesions were significantly smaller
      and had lower TDR (%) than ALK fusion-negative (AN) lesions (tumor diameter: 20.7
      mm +/- 14.1 mm vs. 27.4 mm +/- 13.8 mm, respectively, p <0.01; TDR: 22.8% +/-
      24.8% vs. 44.8% +/- 33.2%, respectively, p <0.01). All AP lesions >20 mm (n = 7,
      25.9%) showed a solid pattern. Among all small lesions, AP lesions had lower TDR
      and more frequent spiculation than AN lesions (p <0.01). Among solid lesions, AP
      lesions were smaller than AN lesions (p = 0.01). CONCLUSION: AP lung lesions were
      significantly smaller and had a lower TDR than AN lesions. Spiculation was more
      frequent in small lesions. Non-solid >20 mm lesions may be ALK fusion-negative.

PMID- 24899138
TI  - Retraction: Synthetic N-acetyl-D-glucosamine based fully branched
      tetrasaccharide, a mimetic of the endogenous ligand for CD69, activates CD69+
      killer lymphocytes upon dimerization via a hydrophilic flexible linker. Journal
      of Medicinal Chemistry 2010, 53, 4050-65.

PMID- 24899139
TI  - Visualizing the structural evolution of LSM/xYSZ composite cathodes for SOFC by
      in-situ neutron diffraction.
AB  - Thermal stability of composite cathodes for solid oxide fuel cells, the mixtures
      of (La0.8Sr0.2)0.95MnO(3-delta) (LSM) and (Y2O3)(x)(ZrO2)(1-x) (xYSZ, x = 3, 6, 8
      and 10), is determined using in-situ neutron diffraction. Thanks to the most
      advanced high flux neutron source, our work highlights the visualization of the
      phase evolutions in heterogeneous material systems at high temperatures, along
      with the analysis of the diffusion activities of transition metal ions that
      reveal the reaction mechanism and kinetics. It is found that the tetragonal-to
      cubic phase transition in YSZ at T > 900 degrees C leads to a heterogeneous
      redistribution of Mn ions. The subsequent reaction of LSM and YSZ occurring at T
      > 1100 degrees C is revealed as a three-stage kinetic process, yielding La2Zr2O7,
      SrZrO3 and MnO. The diffusion activities of Y, Mn and La ions in the
      heterogeneous systems at elevated temperatures are derived by the structural
      analysis, and the three-stage reaction of YSZ and LSM is found strongly
      correlated to ions' behaviors as functions of temperature.

PMID- 24899137
TI  - METFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and
      long-term use in obese children and adolescents - study protocol of a randomized
      controlled study.
AB  - BACKGROUND: The prevalence of childhood obesity and insulin resistance is rising,
      increasing the risk of diabetes mellitus type 2. To prevent these complications,
      lifestyle intervention is the corner stone in treatment. However, long-term
      efficacy of lifestyle intervention is questionable. In addition to lifestyle
      intervention, pharmacological treatments have been explored. Metformin has been
      shown to be moderately effective to reduce BMI in obese adolescents with
      hyperinsulinemia. However, data on pharmacokinetics and long-term efficacy and
      safety are lacking as well as an evidence-based dosing regimen for this age
      group. The primary objective of the METFORMIN study is to determine the effect of
      adding metformin treatment to lifestyle intervention in reducing BMI in obese
      adolescents with insulin resistance. In addition, the pharmacokinetics of
      metformin in obese adolescents will be studied. METHODS/DESIGN: The METFORMIN
      study is a multi-centre prospective study that consists of two 18-month phases: a
      double-blind randomized placebo-controlled trial (part 1) and an open-label
      follow-up study (part 2). During part 1, the participants will be given metformin
      1,000 mg or placebo twice daily and will be offered a lifestyle intervention
      programme; 144 participants will be included, 72 in each arm. Primary endpoints
      are reduction in body mass index, insulin resistance, and percentage body fat.
      DISCUSSION: This study will provide data on short- and long-term efficacy and
      safety of metformin and on the pharmacokinetics of metformin in obese
      adolescents. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01487993; EudraCT
      nr. 2010-023980-17. Registration date: 06-01-2011.

PMID- 24899141
TI  - Differential clinicopathologic and genetic features of late-onset amnestic
      dementias.
AB  - Hippocampal sclerosis of the elderly (HpScl) and Alzheimer's disease (AD),
      especially the limbic-predominant subtype (LP-AD), are amnestic syndromes that
      can be difficult to distinguish. To complicate matters, a subset has concomitant
      HpScl and AD (HpScl-AD). We examined a large cohort of autopsy-confirmed cases of
      HpScl, HpScl-AD, LP-AD, and typical AD to identify distinct clinical, genetic,
      and pathologic characteristics. HpScl cases were significantly older at death and
      had a substantially slower rate of cognitive decline than the AD subtypes.
      Genetic analysis revealed that the AD groups (AD, LP-AD, and HpScl-AD) were more
      likely to be APOE epsilon4 carriers. In contrast, the HpScl groups (HpScl and
      HpScl-AD) were more likely to exhibit genetic variants in GRN and TMEM106B that
      are associated with frontotemporal lobar degeneration. The HpScl groups had a
      high frequency of TDP-43 pathology that was most often Type A morphology and
      distribution, while typical AD and LP-AD had a significantly lower frequency of
      TDP-43 pathology that was most often Type B. These results suggest that HpScl and
      AD are pathologically and genetically distinct and non-synergistic
      neurodegenerative processes that present with amnestic dementia. Pure HpScl and
      HpScl with concomitant AD occur most often in elderly individuals. 

PMID- 24899142
TI  - Cell fusion in the brain: two cells forward, one cell back.
AB  - Adult stem cell populations, notably those which reside in the bone marrow, have
      been shown to contribute to several neuronal cell types in the rodent and human
      brain. The observation that circulating bone marrow cells can migrate into the
      central nervous system and fuse with, in particular, cerebellar Purkinje cells
      has suggested, at least in part, a potential mechanism behind this process.
      Experimentally, the incidence of cell fusion in the brain is enhanced with age,
      radiation exposure, inflammation, chemotherapeutic drugs and even selective
      damage to the neurons themselves. The presence of cell fusion, shown by detection
      of increased bi-nucleated neurons, has also been described in a variety of human
      central nervous system diseases, including both multiple sclerosis and
      Alzheimer's disease. Accumulating evidence is therefore raising new questions
      into the biological significance of cell fusion, with the possibility that it
      represents an important means of cell-mediated neuroprotection or rescue of
      highly complex neurons that cannot be replaced in adult life. Here, we discuss
      the evidence behind this phenomenon in the rodent and human brain, with a focus
      on the subsequent research investigating the physiological mechanisms of cell
      fusion underlying this process. We also highlight how these studies offer new
      insights into endogenous neuronal repair, opening new exciting avenues for
      potential therapeutic interventions against neurodegeneration and brain injury. 

PMID- 24899143
TI  - Identification of immunogenic proteins of the bacterium Acinetobacter baumannii
      using a proteomic approach.
AB  - PURPOSE: Acinetobacter baumannii is an important opportunistic pathogen that
      causes pneumoniae, urinary tract infections, and/or septicemia in
      immunocompromised patients. This pathogen is frequently associated with
      nosocomial outbreaks worldwide and has become particularly problematic because of
      its prevalence and resistance patterns to several antibiotics. In the present
      study, we used an immunoproteome-based approach to identify immunogenic proteins
      located on the surface of A. baumannii for the development of a possible
      immunotherapy against this devastating bacterial infection. EXPERIMENTAL DESIGN:
      Sera from patients with A. baumannii infections (n = 50) and from a control group
      of healthy individuals (n = 3) were analyzed for reactivity against A. baumannii
      outer membrane proteins (OMPs) using Western blot analysis. To identify potential
      immunogenic proteins in A. baumannii, OMPs were separated by 2DE, and reactive
      sera from infected patients were randomly selected and divided into two different
      pools, each containing 15 sera. Finally, MALDI-TOF/TOF mass spectrometric
      analysis was employed to identify the corresponding proteins. RESULTS: This
      analysis identified six immunoreactive proteins: OmpA, Omp34kDa, OprC, OprB-like,
      OXA-23, and ferric siderophore receptor protein. Notably, these proteins are
      highly abundant on the bacterial surface and involved in virulence, antibiotic
      resistance, and growth. CONCLUSIONS AND CLINICAL RELEVANCE: Our results support
      the notion that the proteins identified in the present immunoproteome study could
      serve as antigen candidates for the development of vaccines and passive
      immunotherapies against A. baumannii infections.

PMID- 24899140
TI  - Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar
      degeneration.
AB  - Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically
      associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In
      the present study, we analyzed the SQSTM1 coding sequence for mutations in an
      extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD),
      ascertained within the European Early-Onset Dementia consortium. As control
      dataset, we sequenced 1,625 European control individuals and analyzed whole-exome
      sequence data of 2,274 German individuals (total n = 3,899). Association of rare
      SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240
      control alleles. We identified 25 coding variants in FTLD patients of which 10
      have not been described. Fifteen mutations were absent in the control individuals
      (carrier frequency <0.00026) whilst the others were rare in both patients and
      control individuals. When pooling all variants with a minor allele frequency
      <0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant
      association analysis between patients and controls showed no difference over the
      whole protein, but suggested that rare mutations clustering in the UBA domain of
      SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR =
      2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology
      demonstrated that mutations in SQSTM1 associate with widespread neuronal and
      glial phospho-TDP-43 pathology. With this study, we provide further evidence for
      a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and
      showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated
      with TDP-43 pathology. 

PMID- 24899144
TI  - Confinement effects on the dynamic behavior of poly(D,L-lactic acid) upon
      incorporation in alpha-cyclodextrin.
AB  - Inclusion complexes (ICs) composed of alpha-cyclodextrin (alpha-CD) and poly(D,L
      lactic acid) (PDLLA), with 10/24 (IC1) and 15/46 (IC2) (% w/w) of PDLLA
      incorporated/initial PDLLA weight percentage, were prepared and characterized
      mainly by dielectric relaxation spectroscopy (DRS). Bulk PDLLA was also analyzed
      for comparison. DRS was revealed to be a suitable tool to distinguish the
      dynamical response of the PDLLA regions constrained in between alpha-CD channels
      from the fraction incorporated inside channels. While the cooperative alpha
      process undergoes a dramatic depletion shifting to higher temperatures (~4.5 
      degrees C) for the PDLLA interchannels portion, it is suppressed for PDLLA chains
      inside pores. It was demonstrated that the broad secondary relaxation of bulk
      PDLLA is the Johari-Goldstein process (betaJG-process). The detection of its
      analogue in the ICs at higher frequencies, to a greater extent in IC1, is
      interpreted as a true confinement effect where the dimensions of the alpha-CD
      channels interfere with the length scale of the betaJG-process. The limit
      predicted in the framework of the coupling model, where the alpha-relaxation
      transforms in the betaJG-process, seems to be reached in the ICs. Furthermore, it
      was found that the length scale of the additional gamma process only detected in
      the ICs is inferior to inter- or intrachannel dimensions.

PMID- 24899145
TI  - The effect of age on Glasgow Coma Scale score in patients with traumatic brain
      injury.
AB  - IMPORTANCE: The Glasgow Coma Scale (GCS) is used frequently to define the extent
      of neurologic injury in patients with a traumatic brain injury (TBI). Whether age
      affects the predictive ability of the GCS for severity of TBI (determined by the
      Abbreviated Injury Scale [AIS] score) remains unknown. OBJECTIVE: To investigate
      the effect of age on the association between the GCS and anatomic TBI severity.
      DESIGN, SETTING, AND PARTICIPANTS: We examined all patients with a TBI, defined
      by diagnostic codes 850 to 854 from the International Classification of Diseases,
      Ninth Revision, Clinical Modification, who were admitted to 2 level I trauma
      centers from January 1, 2008, through December 31, 2012. EXPOSURES: We compared
      elderly (>=65 years) and younger (18-64 years) adults with TBI. MAIN OUTCOMES AND
      MEASURES: We examined differences by age in GCS category (defined by emergency
      department GCS as severe [3-8], moderate [9-12], or mild [13-15]) at each level
      of TBI severity (head AIS score, 1 [minor] to 5 [critical]). Cochran-Armitage
      chi2 trend tests and stepwise multivariate linear and logistic regression models
      were used. RESULTS: During the study period, 6710 patients had a TBI (aged <65
      years, 73.17%). Significant differences in GCS category by age occurred at each
      AIS score (P <= .01 for all). In particular, among patients with an AIS score of
      5, most of the elderly patients (56.33%) had a mild neurologic deficit (GCS
      score, 13-15), whereas most of the younger patients (63.28%) had a severe
      neurologic deficit (GCS score, 3-8). After adjustment, the younger adults had
      increased odds of presenting with a severe neurologic deficit (GCS score, 3-8) at
      each of the following AIS scores: 1, 4.2 (95% CI, 1.0-17.6; P = .05); 2, 2.0 (1.0
      3.7; P = .04); 3, 2.0 (1.2-3.5; P = .01); 4, 4.6 (2.8-7.5; P < .001); and 5, 3.1
      (2.1-4.6; P < .001). The interaction between age and GCS for anatomic TBI
      severity remained significant after adjustment (estimate, -0.11; P = .005).
      CONCLUSIONS AND RELEVANCE: Age affects the relationship between the GCS score and
      anatomic TBI severity. Elderly TBI patients have better GCS scores than younger
      TBI patients with similar TBI severity. These findings have implications for TBI
      outcomes research and for protocols and research selection criteria that use the
      GCS.

PMID- 24899146
TI  - Clinical application of noninvasive prenatal testing for the detection of
      trisomies 21, 18, and 13: a hospital experience.
AB  - OBJECTIVE: The aim of this study is to report the clinical application of
      noninvasive prenatal testing (NIPT) to detect chromosomal aneuploidies,
      especially trisomies 21, 18, and 13 in Chinese singleton pregnancies. METHODS:
      Pilot validation between NIPT with full karyotyping was conducted blindly on 306
      cases. Subsequently, 7705 pregnancies were offered with NIPT. Follow-up data was
      obtained in all cases. RESULTS: In the validation stage, a total of five NIPT
      positive cases were observed for trisomies 21 and 18, and results were confirmed
      by karyotyping; there were no cases of trisomy 13. Thus, the overall sensitivity
      and specificity in the validation stage was 100%. In 7705 cases, NIPT results
      were obtained in 7701 cases; 66 cases were classified as positive, including 48
      cases of trisomy 21, 14 cases of trisomy 18, and 4 cases of trisomy 13.
      Subsequent karyotyping documented two false positive diagnoses for trisomies 21,
      18, and 13, respectively. Sensitivity and specificity for detection of trisomies
      21 and 18 and 13 were 100% and 99.9%, respectively. Additionally, prenatal
      chromosomal detection for pregnancies with NIPT has shown a gradual increase
      since its implementation. CONCLUSION: Noninvasive prenatal testing allows a more
      suitable and efficient workflow for our patients' needs, together with invasive
      procedures allows a higher prenatal detection of chromosomal aneuploidies.

PMID- 24899147
TI  - Persistent primitive trigeminal artery: analysis of anatomical characteristics
      and clinical significances.
AB  - PURPOSE: The purpose of this study was to evaluate the classification of
      persistent primitive trigeminal artery (PPTA) based on computed tomography (CT)
      angiography, magnetic resonance (MR) angiography, and cerebral angiography and to
      review the clinical significance. MATERIALS AND METHODS: Images obtained by CT
      angiography performed between January 2011 and August 2013, MR angiography
      between January 2005 and January 2013, and cerebral angiography between January
      2003 and November 2012 were analyzed for the presence of a PPTA. The diagnostic
      criterion for a PPTA was an artery that arises from the cavernous internal
      carotid artery and then joins the basilar artery (BA). We classified each PPTA by
      two different methods. First, the PPTA was classified as type 1, 2, 3, or 4
      according to Weon et al.'s classification. Second, the classification of the PPTA
      was also made according to Salas et al.'s proposal, as a medial or lateral type.
      RESULTS: Eighteen of 8,900 patients (0.2%) had a PPTA. Of all 18 patients with a
      PPTA, nine were classified as type 1, two as type 2, six as type 3, and one as
      type 4. Seventeen PPTAs were a lateral type, and one was a medial type. Regarding
      the degree of BA hypoplasia, no hypoplasia was seen in six cases, moderate
      hypoplasia was identified in six cases, and severe hypoplasia was seen in six
      cases. CONCLUSIONS: This study revealed four types of PPTA according to Weon et
      al.'s classification. The presence of a PPTA should be considered by both the
      clinician and the radiologist who interprets the CT angiography, MR angiography,
      and conventional angiograms.

PMID- 24899149
TI  - Osteopontin as a therapeutic target for cancer.
AB  - INTRODUCTION: Cancer is a complex pathological disorder, established as a result
      of accumulation of genetic and epigenetic changes, which lead to adverse
      alterations in the cellular phenotype. Tumor progression involves intricate
      signaling mediated through crosstalk between various growth factors, cytokines
      and chemokines. Osteopontin (OPN), a chemokine-like protein, is involved in
      promotion of neoplastic cancer into higher grade malignancies by regulating
      various facets of tumor progression such as cell proliferation, angiogenesis and
      metastasis. AREAS COVERED: Tumors as well as stroma-derived OPN play key roles in
      various signaling pathways involved in tumor growth, angiogenesis and metastasis.
      OPN derived from tumor-activated macrophages modulates the tumor microenvironment
      and thereby regulate melanoma growth and angiogenesis. OPN also regulates hypoxia
      inducible factor-1alpha-dependent VEGF expression leading to breast tumor growth
      and angiogenesis in response to hypoxia. Thus, a clear understanding of the
      molecular mechanism underlying OPN-mediated regulation will shed light on
      exciting avenues for further investigation of targeted therapies. Silencing of
      OPN using RNAi technology, blocking OPN activity using specific antibodies and
      small-molecule inhibitors might provide novel strategies, which would aid in
      developing effective therapeutics for the treatment of various types of cancer.
      EXPERT OPINION: This review focuses on new possibilities to exploit OPN as a
      tumor and stroma-derived therapeutic target to combat cancer.

PMID- 24899148
TI  - Phase angle for prognostication of survival in patients with advanced cancer:
      preliminary findings.
AB  - BACKGROUND: Accurate survival prediction is essential for decision-making in
      cancer therapies and care planning. Objective physiologic measures may improve
      the accuracy of prognostication. In this prospective study, the authors
      determined the association of phase angle, handgrip strength, and maximal
      inspiratory pressure with overall survival in patients with advanced cancer.
      METHODS: Hospitalized patients with advanced cancer who were seen by palliative
      care specialists for consultation were enrolled. Information regarding phase
      angle, handgrip strength, maximal inspiratory pressure, and known prognostic
      factors including the Palliative Prognostic Score, Palliative Prognostic Index,
      serum albumin, and body composition was collected. Univariate and multivariate
      survival analysis were performed, and the correlation between phase angle and
      other prognostic variables was examined. RESULTS: A total of 222 patients were
      enrolled. The average age of the patients was 55 years (range, 22 years-79
      years); 59% of the patients were female, with a mean Karnofsky performance status
      of 55 and a median overall survival of 106 days (95% confidence interval [95%
      CI], 71 days-128 days). The median survival for patients with phase angle 2 to
      2.9 degrees , 3 to 3.9 degrees , 4 to 4.9 degrees , 5 to 5.9 degrees  and >= 6
      degrees  was 35 days, 54 days, 112 days, 134 days, and 220 days, respectively (P
      = .001). On multivariate analysis, phase angle (hazards ratio [HR], 0.86-per
      degree increase; 95% CI, 0.74-0.99 increase [P = .04]), Palliative Prognostic
      Score (HR, 1.07; 95% CI, 1.02-1.13 [P = .008]), serum albumin (HR, 0.67; 95% CI,
      0.50-0.91 [P = .009]), and fat-free mass (HR, 0.98; 95% CI, 0.96-0.99 [P = .02])
      were found to be significantly associated with survival. Phase angle was found to
      be only weakly (gamma < 0.4) associated with other prognostic variables.
      CONCLUSIONS: Phase angle was found to be a novel predictor of poor survival,
      independent of established prognostic factors, in the advanced cancer setting.
      This objective and noninvasive tool may be useful for bedside prognostication.

PMID- 24899150
TI  - Prosopis: a global assessment of the biogeography, benefits, impacts and
      management of one of the world's worst woody invasive plant taxa.
AB  - Invasive species cause ecological, economic and social impacts and are key
      drivers of global change. This is the case for the genus Prosopis (mesquite;
      Fabaceae) where several taxa are among the world's most damaging invasive
      species. Many contentious issues ('conflicts of interest') surround these taxa,
      and management interventions have not yet sustainably reduced the negative
      impacts. There is an urgent need to better understand the factors that drive
      invasions and shape management actions, and to compare the effectiveness of
      different management approaches. This paper presents a global review of Prosopis,
      focusing on its distribution, impacts, benefits and approaches to management.
      Prosopis was found to occur in a 129 countries globally and many more countries
      are climatically suitable. All areas with naturalized or invasive Prosopis
      species at present are suitable for more taxa and many Asian and Mediterranean
      countries with no records of Prosopis are bioclimatically suitable. Several
      Prosopis species have substantial impacts on biodiversity, ecosystem services,
      and local and regional economies in their native and even more so in their
      invasive ranges; others provide multiple benefits to local communities.
      Management efforts are underway in only a small part of the invaded range.
      Countries where more research has been done are more likely to implement formal
      management than those where little published research is available. Management
      strategies differ among countries; developed nations use mainly mechanical and
      chemical control whereas developing nations tend to apply control through
      utilization approaches. A range of countries are also using biological control.
      Key gaps in knowledge and promising options for management are highlighted. 

PMID- 24899151
TI  - Assessment of prescription opioid intentional exposures across the rural-urban
      continuum in the United States using both population and drug availability rates.
AB  - PURPOSE: Prescription opioid abuse and misuse are a serious problem in the U.S.
      today. Several studies have shown that the epidemic disproportionately affects
      rural areas. This paper uses three different rates to gain a more complete
      picture of opioid abuse in rural areas. METHODS: This study examines prescription
      opioid intentional exposures using opioid classes tracked in the RADARS((r))
      System Poison Center Program. Intentional exposure rates were calculated
      adjusting for population and unique recipients of dispensed drug (URDD). These
      rates were analyzed using time (quarter) and the proportion of a three-digit zip
      code residing in a rural area as covariates. Additionally, the URDD per
      population rate was calculated to examine the proportion of the population
      filling prescriptions for opioids. RESULTS: After adjusting for population,
      intentional exposure cases significantly increased as the proportion of the
      population residing in a rural area increased. However, when adjusting for URDD,
      intentional exposure cases decreased with increasing rural population. The URDD
      per population increased as the proportion of people residing in a rural area
      increased. CONCLUSIONS: Using both population and URDD adjusted intentional
      exposure rates gives a more complete picture of opioid abuse in rural areas.
      Considering product availability can be used to develop opioid abuse prevention
      strategies and further the education of physicians serving rural areas about this
      epidemic.

PMID- 24899152
TI  - Facial paraffinoma treated with a bipolar radiofrequency device.

PMID- 24899153
TI  - Newly isolated mAbs broaden the neutralizing epitope in murine norovirus.
AB  - Here, we report the isolation and functional characterization of mAbs against two
      murine norovirus (MNV) strains, MNV-1 and WU20, which were isolated following
      oral infection of mice. The mAbs were screened for reactivity against the
      respective homologous and heterologous MNV strain by ELISA. Selected mAbs were of
      IgA, IgG1, IgG2a or IgG2b isotype and showed a range of Western blot reactivities
      from non-binding to strong binding, suggesting recognition of conformational and
      linear epitopes. Some of the anti-MNV-1 antibodies neutralized both MNV-1 and
      WU20 infections in culture and in mice, but none of the anti-WU20 mAbs
      neutralized either virus. The non-neutralizing anti-MNV-1 IgG2b antibody 5C4.10
      was mapped to the S domain of the MNV-1 capsid, whilst the epitopes of the
      neutralizing anti-MNV-1 IgA antibodies 2D3.7 and 4F9.4 were mapped to the P
      domain. Generation of neutralization escape viruses showed that two mutations
      (V339I and D348E) in the C'D' loop of the MNV-1 P domain mediated escape from mAb
      2D3.7 and 4F9.4 neutralization. These findings broaden the known neutralizing
      epitopes of MNV to the main surface-exposed loops of the P domain. In addition,
      the current panel of antibodies provides valuable reagents for studying norovirus
      biology and development of diagnostic tools.

PMID- 24899154
TI  - Genetic diversity of circulating Saffold viruses in Pakistan and Afghanistan.
AB  - Human cardioviruses or Saffold viruses (SAFVs) of the family Picornaviridae are
      newly emerging viruses whose genetic and phenotypic diversity are poorly
      understood. We report here the full genome sequence of 11 SAFV genotypes from
      Pakistan and Afghanistan, along with a re-evaluation of their genetic diversity
      and recombination. We detected 88 SAFV from stool samples of 943 acute flaccid
      paralysis cases using reverse transcriptase-PCR targeting the 5' untranslated
      region (UTR). Further characterization based on complete VP1 analysis revealed 71
      SAFVs belonging to 11 genotypes, including three previously unidentified
      genotypes. SAFV showed high genetic diversity and recombination based on
      phylogenetic, pairwise distance distributions and recombination mapping analyses
      performed herein. Phylogenies based on non-structural and UTRs were highly
      incongruent indicating frequent recombination events among SAFVs. We improved the
      SAFV genotyping classification criteria by determining new VP1 thresholds based
      on the principles used for the classification of enteroviruses. For genotype
      assignment, we propose a threshold of 23 and 10 % divergence for VP1 nucleotide
      and amino acid sequences, respectively. Other members of the species Theilovirus,
      such as Thera virus and Theiler's murine encephalomyelitis virus, are difficult
      to classify in the same species as SAFV, because they are genetically distinct
      from SAFV, with 41-56 % aa pairwise distances. The new genetic information
      obtained in this study will improve our understanding of the evolution and
      classification of SAFV.

PMID- 24899155
TI  - Serum lipid responses to weight loss differ between overweight adults with
      familial hypercholesterolemia and those with familial combined hyperlipidemia.
AB  - The effect of weight loss on lipids differs among individuals, although whether
      it can modify the management of hereditary hyperlipidemias has not yet been
      explored. The objective of this study was to examine the effect of weight loss on
      cholesterol metabolism, assessed by circulating noncholesterol sterols, in
      overweight adults with familial hypercholesterolemia (FH) and familial combined
      hyperlipidemia (FCHL). We conducted a 6-mo weight loss intervention in untreated
      individuals (FH: n = 28; FCHL: n = 50) with a body mass index of >25 kg/m(2) and
      mean age of 46.9 +/- 11.3 y, of whom 53.8% were men. A hypocaloric diet was
      implemented and serum lipid analyses, including noncholesterol sterols, were
      assessed. Global significant mean weight losses of 5.7 kg (-6.6%) and 6.6 kg (
      7.6%) were achieved after 3 and 6 mo, respectively. Mean non-HDL cholesterol and
      triglyceride (TG) changes at 3 and 6 mo compared with baseline were -5.8% (P =
      0.004) and -7.1% (P = 0.014), and -30.1% (P < 0.001) and -31.4% (P < 0.001),
      respectively. Among participants who lost >=5% body weight, only significant
      changes in TGs and non-HDL cholesterol were observed in FCHL participants. Sterol
      precursors of cholesterol synthesis decreased significantly by 10.4% at 6 mo in
      FCHL participants, mostly because of a 23.9% lathosterol reduction. Baseline
      synthesis precursors were associated with TG reduction in FCHL participants (P =
      0.039; R(2) = 0.20), and intestinally derived sterols were inversely associated
      with non-HDL cholesterol changes in FH participants (P = 0.036; R(2) = 0.21).
      Thus, FCHL participants had a better lipid-lowering response to weight loss than
      did FH participants. This response was positively associated with baseline
      cholesterol synthesis, which was reduced by weight loss. Our results confirm the
      cholesterol overproduction mechanism of FCHL and its interaction with fat mass,
      while also supporting the differential management of familial hyperlipidemias if
      obesity coexists. This trial was registered at clinicaltrials.gov as NCT01995149.

PMID- 24899157
TI  - Deep RNA sequencing reveals that microRNAs play a key role in lactation in rats.
AB  - Understanding the regulatory contribution of maternal physiology to difficulties
      with lactation is beneficial to both mother and infant. MicroRNAs (miRNAs), a
      type of noncoding RNA, may be involved in the regulation of mammary gland
      development and function. In the present study, a deep RNA sequencing (RNA-seq)
      technique was used to compare the expression profile of miRNAs and mRNAs of 2
      pooled RNA samples from day 1 and day 7 postpartum (n = 1/d) rat (Rattus
      norvegicus) mammary glands to identify key miRNAs and their target genes that may
      control the rate-limiting steps of lactation. A total of 395 and 400 known miRNAs
      were identified in days 1 and 7 postpartum rat mammary samples, respectively.
      Compared with day 1 postpartum, 27 miRNAs were differentially expressed at day 7
      postpartum. The expression differences between lactation periods were further
      analyzed by real-time quantitative polymerase chain reaction (qPCR) (n = 5). The
      DeltaDeltaCt values of rno-miR-30, rno-miR-1, rno-miR-145-3p, rno-miR-142, rno
      miR-7a-5p, rno-miR-3571, rno-miR-224-5p, rno-miR-362-5p, rno-miR-342-3p, rno-miR
      322-3p, rno-miR-18a-5p, and rno-miR-202-5p between the 2 libraries varied from
      0.64 to 9.44; the DeltaDeltaCt values of rno-miR-133, rno-miR-190a-5p, rno-miR
      27a-5p, rno-miR-451-5p, rno-miR-3120, rno-miR-23a-5p, rno-miR-20a-3p, rno-miR-92a
      1-5p, and rno-miR-134-5p between the 2 libraries varied from -1.02 to -4.37 (P <
      0.05). The intersection of the expressed mRNA genes from RNA-seq and putative
      target genes of differentially expressed miRNAs, termed mammary gland target
      genes (MTGs), was analyzed. The results indicated that 1259 MTGs overlapped
      between the 2 gene sets. The expression of 14 randomly selected genes of the MTGs
      was further confirmed by real-time qPCR (R(2) = 0.86, P < 0.01). The
      downregulated MTGs were enriched for the pathways involved in lipid biosynthesis.
      This gene cluster included 24 lipid metabolic process-related genes, which were
      putative targets of 10 differentially expressed miRNAs. These results will be
      helpful in discovering the biologic underpinnings of poor lactation performance
      in women attempting to breastfeed. 

PMID- 24899156
TI  - Avocado consumption enhances human postprandial provitamin A absorption and
      conversion from a novel high-beta-carotene tomato sauce and from carrots.
AB  - Dietary lipids have been shown to increase bioavailability of provitamin A
      carotenoids from a single meal, but the effects of dietary lipids on conversion
      to vitamin A during absorption are essentially unknown. Based on previous animal
      studies, we hypothesized that the consumption of provitamin A carotenoids with
      dietary lipid would enhance conversion to vitamin A during absorption compared
      with the consumption of provitamin A carotenoids alone. Two separate sets of 12
      healthy men and women were recruited for 2 randomized, 2-way crossover studies.
      One meal was served with fresh avocado (Persea americana Mill), cultivated
      variety Hass (delivering 23 g of lipid), and a second meal was served without
      avocado. In study 1, the source of provitamin A carotenoids was a tomato sauce
      made from a novel, high-beta-carotene variety of tomatoes (delivering 33.7 mg of
      beta-carotene). In study 2, the source of provitamin A carotenoids was raw
      carrots (delivering 27.3 mg of beta-carotene and 18.7 mg of alpha-carotene).
      Postprandial blood samples were taken over 12 h, and provitamin A carotenoids and
      vitamin A were quantified in triglyceride-rich lipoprotein fractions to determine
      baseline-corrected area under the concentration-vs.-time curve. Consumption of
      lipid-rich avocado enhanced the absorption of beta-carotene from study 1 by 2.4
      fold (P < 0.0001). In study 2, the absorption of beta-carotene and alpha-carotene
      increased by 6.6- and 4.8-fold, respectively (P < 0.0001 for both). Most notably,
      consumption of avocado enhanced the efficiency of conversion to vitamin A (as
      measured by retinyl esters) by 4.6-fold in study 1 (P < 0.0001) and 12.6-fold in
      study 2 (P = 0.0013). These observations highlight the importance of provitamin A
      carotenoid consumption with a lipid-rich food such as avocado for maximum
      absorption and conversion to vitamin A, especially in populations in which
      vitamin A deficiency is prevalent. This trial was registered at
      clinicaltrials.gov as NCT01432210. 

PMID- 24899158
TI  - Increasing protein intake modulates lipid metabolism in healthy young men and
      women consuming a high-fat hypercaloric diet.
AB  - The objective of this study was to evaluate the effect of increasing protein
      intake, at the expense of carbohydrates, on intrahepatic lipids (IHLs),
      circulating triglycerides (TGs), and body composition in healthy humans consuming
      a high-fat, hypercaloric diet. A crossover randomized trial with a parallel
      control group was performed. After a 2-wk run-in period, participants were
      assigned to either the control diet [n = 10; 27.8 energy percent (en%) fat, 16.9
      en% protein, 55.3 en% carbohydrates] for 4 wk or a high-fat, hypercaloric diet (n
      = 17; >2 MJ/d) crossover trial with 2 periods of 2 wk, with either high-protein
      (HP) (37.7 en% fat, 25.7 en% protein, 36.6 en% carbohydrates) or normal-protein
      (NP) (39.4 en% fat, 15.4 en% protein, 45.2 en% carbohydrates) content.
      Measurements were performed after 2 wk of run-in (baseline), 2 wk of intervention
      (period 1), and 4 wk of intervention (period 2). A trend toward lower IHL and
      plasma TG concentrations during the HP condition compared with the NP condition
      was observed (IHL: 0.35 +/- 0.04% vs. 0.51 +/- 0.08%, P = 0.08; TG: 0.65 +/- 0.03
      vs. 0.77 +/- 0.05 mmol/L, P = 0.07, for HP and NP, respectively). Fat mass was
      significantly lower (10.6 +/- 1.72 vs. 10.9 +/- 1.73 kg; P = 0.02) with the HP
      diet than with the NP diet, whereas fat-free mass was higher (55.7 +/- 2.79 vs.
      55.2 +/- 2.80 kg; P = 0.003). This study indicated that an HP, high-fat,
      hypercaloric diet affects lipid metabolism. It tends to lower the IHL and
      circulating TG concentrations and significantly lowers fat mass and increases fat
      free mass compared with an NP, high-fat, hypercaloric diet. This trail was
      registered at www.clinicaltrials.gov as NCT01354626.

PMID- 24899159
TI  - Curcumin attenuates D-galactosamine/lipopolysaccharide-induced liver injury and
      mitochondrial dysfunction in mice.
AB  - Curcumin, a naturally occurring antioxidant, has various beneficial effects in
      the treatment of human diseases. However, little information regarding the
      protection it provides against acute liver injury is available. The present study
      investigated the protective effects of curcumin against D-galactosamine (D
      GalN)/lipopolysaccharide (LPS)-induced acute liver injury in mice. A total of 40
      male Kunming mice were randomly assigned to 5 groups: 1) mice administered saline
      vehicle injection (control), 2) mice administered 200 mg/kg body weight (BW)
      curcumin by i.p. injection (CUR), 3) mice administered D-GalN/LPS (700 mg and 5
      MUg/kg BW) via i.p. injection (GL), 4) mice administered 200 mg/kg BW curcumin
      i.p. 1 h before D-GalN/LPS injection (CUR-GL), and 5) mice administered 200 mg/kg
      BW curcumin i.p. 1 h after D-GalN/LPS injection (GL-CUR). Twenty h after D
      GalN/LPS injection, serum alanine aminotransferase activities were 18.5% and
      13.5% lower (P < 0.05) and aspartate aminotransferase (AST) activities were 26.6%
      and 9.6% lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in
      the GL group. The CUR-GL and GL-CUR groups had 64.4% and 15.0% higher (P < 0.05)
      mitochondrial membrane potentials, respectively, and the CUR-GL group had a 44.7%
      lower reactive oxygen species concentration than the GL group (P < 0.05).
      Mitochondrial manganese superoxide dismutase activities were 111% and 77.9%
      higher (P < 0.05) and the percentages of necrotic cells were 47.0% and 32.4%
      lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in the GL
      group. Liver mRNA levels of sirtuin 1 (Sirt1) were 56.4% lower (P < 0.05) in the
      CUR-GL group than in the GL group. Moreover, compared with the GL-CUR group, the
      CUR-GL group had an 18.7% lower serum AST activity, a 31.7% lower mitochondrial
      malondialdehyde concentration, a 36.0% lower hepatic reactive oxygen species
      concentration, and a 43.0% higher mitochondrial membrane potential. These results
      suggested that curcumin protects against D-GalN/LPS-induced liver damage by the
      enhancing antioxidant defense system, attenuating mitochondrial dysfunction and
      inhibiting apoptosis. This was especially true for curcumin pretreatment, which
      highlighted its promise as a preventive treatment for acute liver injury in
      clinical settings.

PMID- 24899160
TI  - Lutein supplementation increases breast milk and plasma lutein concentrations in
      lactating women and infant plasma concentrations but does not affect other
      carotenoids.
AB  - Lutein is a carotenoid that varies in breast milk depending on maternal intake.
      Data are lacking with regard to the effect of dietary lutein supplementation on
      breast milk lutein concentration during lactation and subsequent plasma lutein
      concentration in breast-fed infants. This study was conducted to determine the
      impact of lutein supplementation in the breast milk and plasma of lactating women
      and in the plasma of breast-fed infants 2-3 mo postpartum. Lutein is the dominant
      carotenoid in the infant brain and the major carotenoid found in the retina of
      the eye. Eighty-nine lactating women 4-6 wk postpartum were randomly assigned to
      be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose),
      or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while
      mothers followed their usual diets. Breast milk carotenoids were measured weekly
      by HPLC, and maternal plasma carotenoid concentrations were measured at the
      beginning and end of the study. Infant plasma carotenoid concentrations were
      assessed at the end of the study. No significant differences were found between
      dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk
      and plasma or body mass index at baseline. Total lutein + zeaxanthin
      concentrations were greater in the low- and high-dose-supplemented groups than in
      the placebo group in breast milk (140% and 250%, respectively; P < 0.0001),
      maternal plasma (170% and 250%, respectively; P < 0.0001), and infant plasma
      (180% and 330%, respectively; P < 0.05). Lutein supplementation did not affect
      other carotenoids in lactating women or their infants. Lactating women are highly
      responsive to lutein supplementation, which affects plasma lutein concentrations
      in the infant. This trial was registered at clinicaltrials.gov as NCT01747668. 

PMID- 24899163
TI  - Solution processed, white emitting tandem organic light-emitting diodes with
      inverted device architecture.
AB  - Fully solution processed monochromatic and white-light emitting tandem or multi
      photon polymer OLEDs with an inverted device architecture have been realized by
      employing WO3 /PEDOT:PSS/ZnO/PEI charge carrier generation layers. The luminance
      of the sub-OLEDs adds up in the stacked device indicating multi-photon emission.
      The white OLEDs exhibit a CRI of 75. 

PMID- 24899164
TI  - A new HLA-A*24 allele, HLA-A*24:02:87, identified by sequencing-based typing in a
      Chinese volunteer bone marrow donor.
AB  - Novel allele HLA-A*24:02:87 has one nucleotide change with A*24:02:01:01 in exon
      3 at position 594 C>T. 

PMID- 24899165
TI  - [eHealth and mHealth: current developments in 2014 and perspectives in oncology].
AB  - New information technologies and communication in health or "eHealth" is a way of
      improvement for management of chronic diseases. EHealth can improve patient care
      and care coordination especially in cancer patients who require a
      multidisciplinary approach. Treatments in oncology are complex and can result in
      new toxicities. Information of patients and of caregivers is a crucial issue. The
      patients require to be monitored and the caregivers need up-to-date information.
      The mobile component of eHealth: the mobile health or "mHealth" could provide to
      this need. This paper proposes to expose the principles of eHealth and its mobile
      component mHealth then to discuss their place in the management of cancer, for
      patients and caregivers. 

PMID- 24899162
TI  - Pleiotropy can be effectively estimated without counting phenotypes through the
      rank of a genotype-phenotype map.
AB  - Although pleiotropy, the capability of a gene to affect multiple phenotypes, has
      been well known as one of the common gene properties, a quantitative estimation
      remains a great challenge, simply because of the phenotype complexity. Not
      surprisingly, it is hard for general readers to understand how, without counting
      phenotypes, gene pleiotropy can be effectively estimated from the genetics data.
      In this article we extensively discuss the Gu-2007 method that estimated
      pleiotropy from the protein sequence analysis. We show that this method is
      actually to estimate the rank (K) of genotype-phenotype mapping that can be
      concisely written as K = min(r, Pmin), where Pmin is the minimum pleiotropy among
      all legitimate measures including the fitness components, and r is the rank of
      mutational effects of an amino acid site. Together, the effective gene pleiotropy
      (Ke) estimated by the Gu-2007 method has the following meanings: (i) Ke is an
      estimate of K = min(r, Pmin), the rank of a genotype-phenotype map; (ii) Ke is an
      estimate for the minimum pleiotropy Pmin only if Pmin < r; (iii) the Gu-2007
      method attempted to estimate the pleiotropy of amino acid sites, a conserved
      proxy to the true gene pleiotropy; (iv) with a sufficiently large phylogeny such
      that the rank of mutational effects at an amino acid site is r -> 19, one can
      estimate Pmin between 1 and 19; and (v) Ke is a conserved estimate of K because
      those slightly affected components in fitness have been effectively removed by
      the estimation procedure. In addition, we conclude that mutational pleiotropy
      (number of traits affected by a single mutation) cannot be estimated without
      knowing the phenotypes. 

PMID- 24899166
TI  - Synthesis of DIBAC analogues with excellent SPAAC rate constants.
AB  - In search for increased reactivity in strain-promoted azide alkyne cycloadditions
      (SPAAC), the synthesis of new and more reactive cyclooctynes is of pivotal
      importance. To identify cyclooctynes with enhanced reactivity, without loss of
      stability, the synthesis and kinetic analysis of new dibenzoazacyclooctyne
      (DIBAC) analogues were conducted. Starting from iodobenzyl alcohol analogues and
      ortho-ethynylaniline various substituted dihydrodibenzo[b,f]azocines were
      produced. Subsequent bromination and elimination proved to be difficult depending
      on the aromatic substitution pattern, yielding chloro-, bromo-, and methoxy
      substituted DIBACs in moderate yield. In the elimination reaction towards nitro-
      and Br,Cl-DIBAC, the corresponding cyclooctene was obtained instead of the
      cyclooctyne. Additionally, a dimethoxy-substituted DIBAC analogue was prepared
      following an alternative route involving light-induced deprotection of a
      cyclopropenone derivative. In total, four DIBAC analogues were successfully
      prepared showing excellent rate constants in the SPAAC reaction ranging from 0.45
      to 0.9 M(-1) s(-1), which makes them comparable to the fastest cyclooctynes
      currently known. 

PMID- 24899161
TI  - Apical accumulation of the Sevenless receptor tyrosine kinase during Drosophila
      eye development is promoted by the small GTPase Rap1.
AB  - The Ras/MAPK-signaling pathway plays pivotal roles during development of
      metazoans by controlling cell proliferation and cell differentiation elicited, in
      several instances, by receptor tyrosine kinases (RTKs). While the internal
      mechanism of RTK-driven Ras/MAPK signaling is well understood, far less is known
      regarding its interplay with other co-required signaling events involved in
      developmental decisions. In a genetic screen designed to identify new regulators
      of RTK/Ras/MAPK signaling during Drosophila eye development, we identified the
      small GTPase Rap1, PDZ-GEF, and Canoe as components contributing to Ras/MAPK
      mediated R7 cell differentiation. Rap1 signaling has recently been found to
      participate in assembling cadherin-based adherens junctions in various fly
      epithelial tissues. Here, we show that Rap1 activity is required for the
      integrity of the apical domains of developing photoreceptor cells and that
      reduced Rap1 signaling hampers the apical accumulation of the Sevenless RTK in
      presumptive R7 cells. It thus appears that, in addition to its role in cell-cell
      adhesion, Rap1 signaling controls the partitioning of the epithelial cell
      membrane, which in turn influences signaling events that rely on apico-basal cell
      polarity.

PMID- 24899167
TI  - System and measurement method for binocular pupillometry to study pupil size
      variability.
AB  - BACKGROUND: An objective and noninvasive examination of pupil size variability
      can be used to assess the activity of the autonomous nervous system. We designed
      a system that enables binocular, fast, and accurate recordings of different types
      of pupil variabilities, which are synchronous with other biosignals. This type of
      measurement system is needed to extend the scope of pupillometry applications.
      METHODS: In the proposed system, the left and right eyes are independently and
      interchangeably illuminated to generate alternating images, which are
      successively acquired by a single camera. The system is composed of four
      functional modules: the image acquisition module, the image processing unit, the
      light stimulator, and the controller. The proposed image processing algorithm
      approximates the shape of the pupil using the best-fit ellipse. The user control
      panel (controller) precisely sets the stimuli parameters and controls the entire
      measurement procedure. RESULTS: The computer-based binocular system records the
      pupil size during the pupil light reflexes (direct and indirect) and spontaneous
      pupil size fluctuations, at a sampling rate up to 75 Hz, with a resolution better
      than 0.02 mm. Our initial laboratory tests confirmed that the new system is fast
      and precise (system accuracy better than 0.5% and repeatability better than 4%).
      CONCLUSIONS: The proposed system's unique geometry and construction, and the
      method it uses to detect images from each eye, allows us to monitor the right and
      left eyes using a single camera with no overlap between the images. The system
      does not require a very experienced operator, because it is relatively simple and
      easy to use. Importantly, it is comfortable for the subjects. Additionally, the
      presented system can operate with other bio-measurement systems using a
      synchronous signal. These system capabilities can expand the scope of
      pupillometry research applications.

PMID- 24899168
TI  - Increased expression of vascular endothelial growth factor in a case of protein
      losing enteropathy with undifferentiated connective tissue disease.

PMID- 24899169
TI  - The direct and indirect effects of a glyphosate-based herbicide and nutrients on
      Chironomidae (Diptera) emerging from small wetlands.
AB  - Laboratory and mesocosm experiments have demonstrated that some glyphosate-based
      herbicides can have negative effects on benthic invertebrate species. Although
      these herbicides are among the most widely used in agriculture, there have been
      few multiple-stressor, natural system-based investigations of the impacts of
      glyphosate-based herbicides in combination with fertilizers on the emergence
      patterns of chironomids from wetlands. Using a replicated, split-wetland
      experiment, the authors examined the effects of 2 nominal concentrations (2.88 mg
      acid equivalents/L and 0.21 mg acid equivalents/L) of the glyphosate herbicide
      Roundup WeatherMax, alone or in combination with nutrient additions, on the
      emergence of Chironomidae (Diptera) before and after herbicide-induced damage to
      macrophytes. There were no direct effects of treatment on the structure of the
      Chironomidae community or on the overall emergence rates. However, after
      macrophyte cover declined as a result of herbicide application, there were
      statistically significant increases in emergence in all but the highest herbicide
      treatment, which had also received no nutrients. There was a negative
      relationship between chironomid abundance and macrophyte cover on the treated
      sides of wetlands. Fertilizer application did not appear to compound the effects
      of the herbicide treatments. Although direct toxicity of Roundup WeatherMax was
      not apparent, the authors observed longer-term impacts, suggesting that the
      indirect effects of this herbicide deserve more consideration when assessing the
      ecological risk of using herbicides in proximity to wetlands.

PMID- 24899170
TI  - Prelinguistic infants are sensitive to space-pitch associations found across
      cultures.
AB  - People often talk about musical pitch using spatial metaphors. In English, for
      instance, pitches can be "high" or "low" (i.e., height-pitch association),
      whereas in other languages, pitches are described as "thin" or "thick" (i.e.,
      thickness-pitch association). According to results from psychophysical studies,
      metaphors in language can shape people's nonlinguistic space-pitch
      representations. But does language establish mappings between space and pitch in
      the first place, or does it only modify preexisting associations? To find out, we
      tested 4-month-old Dutch infants' sensitivity to height-pitch and thickness-pitch
      mappings using a preferential-looking paradigm. The infants looked significantly
      longer at cross-modally congruent stimuli for both space-pitch mappings, which
      indicates that infants are sensitive to these associations before language
      acquisition. The early presence of space-pitch mappings means that these
      associations do not originate from language. Instead, language builds on
      preexisting mappings, changing them gradually via competitive associative
      learning. Space-pitch mappings that are language-specific in adults develop from
      mappings that may be universal in infants. 

PMID- 24899171
TI  - Serum magnesium concentration is inversely associated with fibroblast growth
      factor 23 in haemodialysis patients.
AB  - AIM: Fibroblast growth factor 23 is reported to be a pivotal regulator for the
      chronic kidney disease-mineral bone disorders, working in coordinated ways with
      phosphate, calcium, and parathyroid hormone. However, whether there is a
      relationship between fibroblast growth factor 23 and magnesium is currently
      unclear. To address this, we performed a cross-sectional observational study in
      haemodialysis patients. METHODS: We measured the serum levels of fibroblast
      growth factor 23, magnesium and other factors that are implicated in chronic
      kidney disease-mineral bone disorders in 225 haemodialysis patients. RESULTS:
      Simple correlation analysis showed that fibroblast growth factor 23 was not
      correlated with magnesium. However, upon multiple regression analysis, a
      significant negative correlation was found between fibroblast growth factor 23
      and magunesium (b = -0.164, P = 0.0020). Moreover, the levels of fibroblast
      growth factor 23 in patients treated with magnesium oxide had significantly lower
      levels than those without magnesium oxide. CONCLUSION: We speculate that the
      magnesium is a potential regulator of fibroblast growth factor 23 levels in
      haemodialysis patients. Our data suggest that follow-up studies to elucidate the
      molecular mechanisms that underlie this relationship are warranted.

PMID- 24899172
TI  - Modification of the hepatitis B virus envelope protein glycosylation pattern
      interferes with secretion of viral particles, infectivity, and susceptibility to
      neutralizing antibodies.
AB  - The envelope proteins of hepatitis B virus (HBV) bear an N-linked glycosylation
      site at N146 within the immunodominant a-determinant in the antigenic loop (AGL)
      region. This glycosylation site is never fully functional, leading to a nearly
      1/1 ratio of glycosylated/nonglycosylated isoforms in the viral envelope. Here we
      investigated the requirement for a precise positioning of N-linked glycan at
      amino acid 146 and the functions associated with the glycosylated and
      nonglycosylated isoforms. We observed that the removal of the N146 glycosylation
      site by mutagenesis was permissive to envelope protein synthesis and stability
      and to secretion of subviral particles (SVPs) and hepatitis delta virus (HDV)
      virions, but it was detrimental to HBV virion production. Several positions in
      the AGL could substitute for position 146 as the glycosylation acceptor site. At
      position 146, neither a glycan chain nor asparagine was absolutely required for
      infectivity, but there was a preference for a polar residue. Envelope proteins
      bearing 5 AGL glycosylation sites became hyperglycosylated, leading to an
      increased capacity for SVP secretion at the expense of HBV and HDV virion
      secretion. Infectivity-compatible N-glycosylation sites could be inserted at 3
      positions (positions 115, 129, and 136), but when all three positions were
      glycosylated, the hyperglycosylated mutant was substantially attenuated at viral
      entry, while it acquired resistance to neutralizing antibodies. Taken together,
      these findings suggest that the nonglycosylated N146 is essential for
      infectivity, while the glycosylated form, in addition to its importance for HBV
      virion secretion, is instrumental in shielding the a-determinant from
      neutralizing antibodies. IMPORTANCE: At the surface of HBV particles, the
      immunodominant a-determinant is the main target of neutralizing antibodies and an
      essential determinant of infectivity. It contains an N-glycosylation site at
      position 146, which is functional on only half of the envelope proteins. Our data
      suggest that the coexistence of nonglycosylated and glycosylated N146 at the
      surface of HBV reflects the dual function of this determinant in infectivity and
      immune escape. Hence, a modification of the HBV glycosylation pattern affects not
      only virion assembly and infectivity but also immune escape.

PMID- 24899173
TI  - MicroRNA miR-BART20-5p stabilizes Epstein-Barr virus latency by directly
      targeting BZLF1 and BRLF1.
AB  - Epstein-Barr virus (EBV) is a human herpesvirus associated with various tumors.
      Rather than going through the lytic cycle, EBV maintains latency by limiting the
      expression of viral genes in tumors. Viral microRNAs (miRNAs) of some
      herpesviruses have been reported to directly target immediate early genes and
      suppress lytic induction. In this study, we investigated whether BamHI-A
      rightward transcript (BART) miRNAs targeted two EBV immediate early genes, BZLF1
      and BRLF1. Bioinformatic analysis predicted that 12 different BART miRNAs would
      target BRLF1. Of these, the results of a luciferase reporter assay indicated that
      only one interacted with the 3' untranslated region (UTR) of BRLF1: miR-BART20
      5p. miR-BART20-5p's effect on gene expression involved two putative seed match
      sites in the BRLF1 3' UTR, but a mutant version of the miRNA, miR-BART20-5pm, had
      no effect on expression. As expected from the fact that the entire 3' UTR of
      BZLF1 resides within the 3' UTR of BRLF1, miR-BART20-5p interacted with the 3'
      UTR of BZLF1 as well. BZLF1 and BRLF1 mRNA and protein expression was suppressed
      in cells of an AGS cell line infected with the recombinant Akata strain of EBV
      (AGS-EBV) transfected with a miR-BART20-5p mimic. The expression of various EBV
      early proteins was also suppressed by the miR-BART20-5p mimic. In contrast, BZLF1
      and BRLF1 expression in AGS-EBV cells transfected with a miR-BART20-5p inhibitor
      was enhanced. Furthermore, progeny virus production was suppressed by the miR
      BART20-5p mimic and enhanced by the miR-BART20-5p inhibitor in AGS-EBV cells
      induced for the lytic cycle. Our data suggest that miR-BART20-5p plays a key role
      in latency maintenance in EBV-associated tumors by directly targeting immediate
      early genes. IMPORTANCE: Herpesviruses maintain latency using various mechanisms
      and establish lifelong infection in the host. From time to time, herpesviruses
      are reactivated and express immediate early genes which trigger a lytic cascade,
      leading to the production of progeny viruses. Recently, some herpesviruses have
      been shown to use their own microRNAs (miRNAs) to downregulate immediate early
      genes to inhibit the lytic cycle. This study presents evidence that EBV also
      downregulates two immediate early genes by miR-BART20-5p to suppress the lytic
      cycle and progeny virus production. Overall, this is the first study to report
      the direct regulation of EBV immediate early genes by an EBV miRNA, implying its
      likely importance in latency maintenance in EBV-associated tumors.

PMID- 24899174
TI  - Quantitative proteomic analysis of the influenza A virus nonstructural proteins
      NS1 and NS2 during natural cell infection identifies PACT as an NS1 target
      protein and antiviral host factor.
AB  - Influenza A virus (IAV) replication depends on the interaction of virus proteins
      with host factors. The viral nonstructural protein 1 (NS1) is essential in this
      process by targeting diverse cellular functions, including mRNA splicing and
      translation, cell survival, and immune defense, in particular the type I
      interferon (IFN-I) response. In order to identify host proteins targeted by NS1,
      we established a replication-competent recombinant IAV that expresses epitope
      tagged forms of NS1 and NS2, which are encoded by the same gene segment, allowing
      purification of NS proteins during natural cell infection and analysis of
      interacting proteins by quantitative mass spectrometry. We identified known NS1-
      and NS2-interacting proteins but also uncharacterized proteins, including PACT,
      an important cofactor for the IFN-I response triggered by the viral RNA-sensor
      RIG-I. We show here that NS1 binds PACT during virus replication and blocks
      PACT/RIG-I-mediated activation of IFN-I, which represents a critical event for
      the host defense. Protein interaction and interference with IFN-I activation
      depended on the functional integrity of the highly conserved RNA binding domain
      of NS1. A mutant virus with deletion of NS1 induced high levels of IFN-I in
      control cells, as expected; in contrast, shRNA-mediated knockdown of PACT
      compromised IFN-I activation by the mutant virus, but not wild-type virus, a
      finding consistent with the interpretation that PACT (i) is essential for IAV
      recognition and (ii) is functionally compromised by NS1. Together, our data
      describe a novel approach to identify virus-host protein interactions and
      demonstrate that NS1 interferes with PACT, whose function is critical for robust
      IFN-I production. IMPORTANCE: Influenza A virus (IAV) is an important human
      pathogen that is responsible for annual epidemics and occasional devastating
      pandemics. Viral replication and pathogenicity depends on the interference of
      viral factors with components of the host defense system, particularly the type I
      interferon (IFN-I) response. The viral NS1 protein is known to counteract virus
      recognition and IFN-I production, but the molecular mechanism is only partially
      defined. We used a novel proteomic approach to identify host proteins that are
      bound by NS1 during virus replication and identified the protein PACT, which had
      previously been shown to be involved in virus-mediated IFN-I activation. We find
      that NS1 prevents PACT from interacting with an essential component of the virus
      recognition pathway, RIG-I, thereby disabling efficient IFN-I production. These
      observations provide an important piece of information on how IAV efficiently
      counteracts the host immune defense.

PMID- 24899175
TI  - Absence of genetic differences among G10P[11] rotaviruses associated with
      asymptomatic and symptomatic neonatal infections in Vellore, India.
AB  - Rotaviruses (RVs) are leading causes of severe diarrhea and vomiting in infants
      and young children. RVs with G10P[11] genotype specificity have been associated
      with symptomatic and asymptomatic neonatal infections in Vellore, India. To
      identify possible viral genetic determinants responsible for differences in
      symptomology, the genome sequences of G10P[11] RVs in stool samples of 19
      neonates with symptomatic infections and 20 neonates with asymptomatic infections
      were determined by Sanger and next-generation sequencing. The data showed that
      all 39 viruses had identical genotype constellations (G10-P[11]-I2-R2-C2-M2-A1-N1
      T1-E2-H3), the same as those of the previously characterized symptomatic N155
      Vellore isolate. The data also showed that the RNA and deduced protein sequences
      of all the Vellore G10P[11] viruses were nearly identical; no nucleotide or amino
      acid differences were found that correlated with symptomatic versus asymptomatic
      infection. Next-generation sequencing data revealed that some stool samples, both
      from neonates with symptomatic infections and from neonates with asymptomatic
      infections, also contained one or more positive-strand RNA viruses (Aichi virus,
      astrovirus, or salivirus/klassevirus) suspected of being potential causes of
      pediatric gastroenteritis. However, none of the positive-strand RNA viruses could
      be causally associated with the development of symptoms. These results indicate
      that the diversity of clinical symptoms in Vellore neonates does not result from
      genetic differences among G10P[11] RVs; instead, other undefined factors appear
      to influence whether neonates develop gastrointestinal disease symptoms.
      IMPORTANCE: Rotavirus (RV) strains have been identified that preferentially
      replicate in neonates, in some cases, without causing gastrointestinal disease.
      Surveillance studies have established that G10P[11] RVs are a major cause of
      neonatal infection in Vellore, India, with half of infected neonates exhibiting
      symptoms. We used Sanger and next-generation sequencing technologies to contrast
      G10P[11] RVs recovered from symptomatic and asymptomatic neonates. Remarkably,
      the data showed that the RNA genomes of the viruses were virtually
      indistinguishable and lacked any differences that could explain the diversity of
      clinical outcomes among infected Vellore neonates. The sequencing results also
      indicated that some symptomatic and some asymptomatic Vellore neonates were
      infected with other enteric viruses (Aichi virus, astrovirus,
      salvirus/klassevirus); however, none could be correlated with the presence of
      symptoms in neonates. Together, our findings suggest that other poorly defined
      factors, not connected to the genetic makeup of the Vellore G10P[11] viruses,
      influence whether neonates develop gastrointestinal disease symptoms.

PMID- 24899176
TI  - Predicted structure and domain organization of rotavirus capping enzyme and
      innate immune antagonist VP3.
AB  - Rotaviruses and orbiviruses are nonturreted Reoviridae members. The rotavirus VP3
      protein is a multifunctional capping enzyme and antagonist of the interferon
      induced cellular oligoadenylate synthetase-RNase L pathway. Despite mediating
      important processes, VP3 is the sole protein component of the rotavirus virion
      whose structure remains unknown. In the current study, we used sequence alignment
      and homology modeling to identify features common to nonturreted Reoviridae
      capping enzymes and to predict the domain organization, structure, and active
      sites of rotavirus VP3. Our results suggest that orbivirus and rotavirus capping
      enzymes share a domain arrangement similar to that of the bluetongue virus
      capping enzyme. Sequence alignments revealed conserved motifs and suggested that
      rotavirus and orbivirus capping enzymes contain a variable N-terminal domain, a
      central guanine-N7-methyltransferase domain that contains an additional inserted
      domain, and a C-terminal guanylyltransferase and RNA 5'-triphosphatase domain.
      Sequence conservation and homology modeling suggested that the insertion in the
      guanine-N7-methyltransferase domain is a ribose-2'-O-methyltransferase domain for
      most rotavirus species. Our analyses permitted putative identification of
      rotavirus VP3 active-site residues, including those that form the ribose-2'-O
      methyltransferase catalytic tetrad, interact with S-adenosyl-l-methionine, and
      contribute to autoguanylation. Previous reports have indicated that group A
      rotavirus VP3 contains a C-terminal 2H-phosphodiesterase domain that can cleave
      2'-5' oligoadenylates, thereby preventing RNase L activation. Our results suggest
      that a C-terminal phosphodiesterase domain is present in the capping enzymes from
      two additional rotavirus species. Together, these findings provide insight into a
      poorly understood area of rotavirus biology and are a springboard for future
      biochemical and structural studies of VP3. IMPORTANCE: Rotaviruses are an
      important cause of severe diarrheal disease. The rotavirus VP3 protein caps viral
      mRNAs and helps combat cellular innate antiviral defenses, but little is known
      about its structure or enzymatic mechanisms. In this study, we used sequence- and
      structure-based alignments with related proteins to predict the structure of VP3
      and identify enzymatic domains and active sites therein. This work provides
      insight into the mechanisms of rotavirus transcription and evasion of host innate
      immune defenses. An improved understanding of these processes may aid our ability
      to develop rotavirus vaccines and therapeutics.

PMID- 24899177
TI  - Transfer of the amino-terminal nuclear envelope targeting domain of human MX2
      converts MX1 into an HIV-1 resistance factor.
AB  - The myxovirus resistance 2 (MX2) protein of humans has been identified recently
      as an interferon (IFN)-inducible inhibitor of human immunodeficiency virus type 1
      (HIV-1) that acts at a late postentry step of infection to prevent the nuclear
      accumulation of viral cDNA (C. Goujon et al., Nature 502:559-562, 2013,
      http://dx.doi.org/10.1038/nature12542; M. Kane et al., Nature 502:563-566, 2013,
      http://dx.doi.org/10.1038/nature12653; Z. Liu et al., Cell Host Microbe 14:398
      410, 2013, http://dx.doi.org/10.1016/j.chom.2013.08.015). In contrast, the
      closely related human MX1 protein, which suppresses infection by a range of RNA
      and DNA viruses (such as influenza A virus [FluAV]), is ineffective against HIV
      1. Using a panel of engineered chimeric MX1/2 proteins, we demonstrate that the
      amino-terminal 91-amino-acid domain of MX2 confers full anti-HIV-1 function when
      transferred to the amino terminus of MX1, and that this fusion protein retains
      full anti-FluAV activity. Confocal microscopy experiments further show that this
      MX1/2 fusion, similar to MX2 but not MX1, can localize to the nuclear envelope
      (NE), linking HIV-1 inhibition with MX accumulation at the NE. MX proteins are
      dynamin-like GTPases, and while MX1 antiviral function requires GTPase activity,
      neither MX2 nor MX1/2 chimeras require this attribute to inhibit HIV-1. This key
      discrepancy between the characteristics of MX1- and MX2-mediated viral
      resistance, together with previous observations showing that the L4 loop of the
      stalk domain of MX1 is a critical determinant of viral substrate specificity,
      presumably reflect fundamental differences in the mechanisms of antiviral
      suppression. Accordingly, we propose that further comparative studies of MX
      proteins will help illuminate the molecular basis and subcellular localization
      requirements for implementing the noted diversity of virus inhibition by MX
      proteins. IMPORTANCE: Interferon (IFN) elicits an antiviral state in cells
      through the induction of hundreds of IFN-stimulated genes (ISGs). The human MX2
      protein has been identified as a key effector in the suppression of HIV-1
      infection by IFN. Here, we describe a molecular genetic approach, using a
      collection of chimeric MX proteins, to identify protein domains of MX2 that
      specify HIV-1 inhibition. The amino-terminal 91-amino-acid domain of human MX2
      confers HIV-1 suppressor capabilities upon human and mouse MX proteins and also
      promotes protein accumulation at the nuclear envelope. Therefore, these studies
      correlate the cellular location of MX proteins with anti-HIV-1 function and help
      establish a framework for future mechanistic analyses of MX-mediated virus
      control.

PMID- 24899178
TI  - Extraribosomal l13a is a specific innate immune factor for antiviral defense.
AB  - We report a novel extraribosomal innate immune function of mammalian ribosomal
      protein L13a, whereby it acts as an antiviral agent. We found that L13a is
      released from the 60S ribosomal subunit in response to infection by respiratory
      syncytial virus (RSV), an RNA virus of the Pneumovirus genus and a serious lung
      pathogen. Unexpectedly, the growth of RSV was highly enhanced in L13a-knocked
      down cells of various lineages as well as in L13a knockout macrophages from mice.
      In all L13a-deficient cells tested, translation of RSV matrix (M) protein was
      specifically stimulated, as judged by a greater abundance of M protein and
      greater association of the M mRNA with polyribosomes, while general translation
      was unaffected. In silico RNA folding analysis and translational reporter assays
      revealed a putative hairpin in the 3'untranslated region (UTR) of M mRNA with
      significant structural similarity to the cellular GAIT (gamma-activated inhibitor
      of translation) RNA hairpin, previously shown to be responsible for assembling a
      large, L13a-containing ribonucleoprotein complex that promoted translational
      silencing in gamma interferon (IFN-gamma)-activated myeloid cells. However, RNA
      protein interaction studies revealed that this complex, which we named VAIT
      (respiratory syncytial virus-activated inhibitor of translation) is functionally
      different from the GAIT complex. VAIT is the first report of an extraribosomal
      L13a-mediated, IFN-gamma-independent innate antiviral complex triggered in
      response to virus infection. We provide a model in which the VAIT complex
      strongly hinders RSV replication by inhibiting the translation of the rate
      limiting viral M protein, which is a new paradigm in antiviral defense.
      IMPORTANCE: The innate immune mechanisms of host cells are diverse in nature and
      act as a broad-spectrum cellular defense against viruses. Here, we report a novel
      innate immune mechanism functioning against respiratory syncytial virus (RSV), in
      which the cellular ribosomal protein L13a is released from the large ribosomal
      subunit soon after infection and inhibits the translation of a specific viral
      mRNA, namely, that of the matrix protein M. Regarding its mechanism, we show that
      the recognition of a specific secondary structure in the 3' untranslated region
      of the M mRNA leads to translational arrest of the mRNA. We also show that the
      level of M protein in the infected cell is rate limiting for viral morphogenesis,
      providing a rationale for L13a to target the M mRNA for suppression of RSV
      growth. Translational silencing of a viral mRNA by a deployed ribosomal protein
      is a new paradigm in innate immunity.

PMID- 24899180
TI  - Structure of influenza virus N7: the last piece of the neuraminidase "jigsaw"
      puzzle.
AB  - There are nine subtypes of influenza A virus neuraminidase (NA), N1 to N9. In
      addition, influenza B virus also contains NA, and there are two influenza virus
      NA-like molecules, N10 and N11, which were recently identified from bats. Crystal
      structures for all of these proteins have been solved, with the exception of N7,
      and there is no published report of N6, although a structure has been deposited
      in the Protein Data Bank. Here, we present the N7 and N6 structures at 2.1 A and
      1.8 A, respectively. Structural comparison of all NA subtypes shows that both N7
      and N6 highly resemble typical group 2 NA structures with some special
      characteristics, including an additional cavity adjacent to their active sites
      formed by novel 340-loop conformations. Comparative analysis also revealed new
      structural insights into the N-glycosylation, calcium binding, and second sialic
      acid binding site of influenza virus NA. This comprehensive study is critical for
      understanding the complexity of the most successful influenza drug target and for
      the structure-based design of novel influenza inhibitors. IMPORTANCE: Influenza
      viruses impose a great burden on society, by the human-adapted seasonal types as
      well as by variants that occasionally jump from the avian reservoir to infect
      humans. The surface glycoprotein neuraminidase (NA) is essential for the
      propagation of the virus and currently the most successfully drug-targeted
      molecule. Therefore, the structural and functional analysis of NA is critical for
      the prevention and control of influenza infections. There are nine subtypes of
      influenza A virus NA (N1 to N9). In addition, influenza B virus also contains NA,
      and there are two influenza NA-like molecules, N10 and N11, which were recently
      identified in bats. Crystal structures for all of these proteins have been solved
      and reported with the exception of N7 and N6. The structural analysis of
      influenza virus N7 and N6 presented in this study therefore completes the puzzle
      and adds to a comprehensive understanding of influenza virus NA.

PMID- 24899179
TI  - The gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and murine
      gammaherpesvirus 68 modulate the Toll-like receptor-induced proinflammatory
      cytokine response.
AB  - The human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), the
      etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and
      multicentric Castleman's disease, establishes lifelong latency upon infection.
      Murine gammaherpesvirus 68 (MHV68) is a well-established model for KSHV. Toll
      like receptors (TLRs) play a crucial role for the innate immune response to
      pathogens. Although KSHV and MHV68 are detected by TLRs, studies suggest they
      modulate TLR4 and TLR9 signaling, respectively. In this study, we show that in
      bone marrow-derived macrophages (BMDMs), MHV68 did not induce a detectable
      proinflammatory cytokine response. Furthermore, MHV68 abrogated the response to
      TLR2, -4, -7, and -9 agonists in BMDMs. Similarly to observations with MHV68,
      infection with KSHV efficiently inhibited TLR2 signaling in THP-1 monocytes.
      Using a KSHV open reading frame (ORF) library, we found that K4.2, ORF21, ORF31,
      and the replication and transcription activator protein (RTA)/ORF50 inhibited
      TLR2-dependent nuclear factor kappa B (NF-kappaB) activation in HEK293 TLR2
      yellow fluorescent protein (YFP)- and Flag-TLR2-transfected HEK293T cells. Of the
      identified ORFs, RTA/ORF50 strongly downregulated TLR2 and TLR4 signaling by
      reducing TLR2 and TLR4 protein expression. Confocal microscopy revealed that TLR2
      and TLR4 were no longer localized to the plasma membrane in cells expressing
      RTA/ORF50. In this study, we have shown that the gammaherpesviruses MHV68 and
      KSHV efficiently downmodulate TLR signaling in macrophages and have identified a
      novel function of RTA/ORF50 in modulation of the innate immune response.
      IMPORTANCE: The Toll-like receptors (TLRs) are an important class of pattern
      recognition receptors of the innate immune system. They induce a potent
      proinflammatory cytokine response upon detection of a variety of pathogens. In
      this study, we found that the gammaherpesviruses murine gammaherpesvirus 68
      (MHV68) and Kaposi's sarcoma-associated herpesvirus (KSHV) efficiently inhibit
      the TLR-mediated innate immune response. We further identified the KSHV-encoded
      replication and transcription activator protein (RTA) as a novel modulator of TLR
      signaling. Our data suggest that the gammaherpesviruses MHV68 and KSHV prevent
      activation of the innate immune response by targeting TLR signaling.

PMID- 24899181
TI  - Binding of the Kaposi's sarcoma-associated herpesvirus to the ephrin binding
      surface of the EphA2 receptor and its inhibition by a small molecule.
AB  - The ephrin receptor tyrosine kinase A2 (EphA2) is an entry receptor for Kaposi's
      sarcoma-associated herpesvirus (KSHV) that is engaged by the virus through its
      gH/gL glycoprotein complex. We describe here that natural ephrin ligands inhibit
      the gH/gL-EphA2 interaction. The effects of point mutations within EphA2
      demonstrated that KSHV gH/gL interacts with EphA2 through a restricted set of the
      same residues that mediate binding of A-type ephrins. Two previously described
      inhibitors of the EphA2 interaction with ephrin A5 also inhibited binding of KSHV
      gH/gL to EphA2. The more potent of the two compounds inhibited KSHV infection of
      blood vessel and lymphatic endothelial cells in the micromolar concentration
      range. Our results demonstrate that interaction of KSHV with EphA2 occurs in a
      fashion similar to that of the natural ephrin ligands. Our data further indicate
      a new avenue for drug development against KSHV. IMPORTANCE: Our study reports two
      important findings. First, we show that KSHV engages its receptor, the receptor
      tyrosine kinase EphA2, at a site that overlaps the binding site of the natural
      ephrin ligands. Second, we demonstrate that KSHV infection of target cells can be
      blocked by a small-molecule inhibitor of the viral glycoprotein-EphA2
      interaction. These findings represent a novel avenue for the development of
      strategies to treat KSHV-associated diseases.

PMID- 24899184
TI  - Functional analyses of the three simian hemorrhagic fever virus nonstructural
      protein 1 papain-like proteases.
AB  - The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural
      polyprotein 1a is predicted to encode three papain-like proteases (PLP1alpha,
      PLP1beta, and PLP1gamma). Catalytic residues and cleavage sites for each of the
      SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with
      each other as well as with those of other arteriviruses, and the predicted
      catalytic residues were shown to be proximal by homology modeling of the SHFV
      nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal
      structures. The functionality of the predicted catalytic Cys residues and
      cleavage sites was tested by analysis of the autoproteolytic products generated
      in in vitro transcription/translation reactions done with wild-type or mutant
      SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy
      analysis of selected immunoprecipitated cleavage products. The data showed that
      each of the three SHFV PLP1s is an active protease. Cys63 was identified as the
      catalytic Cys of SHFV PLP1alpha and is adjacent to an Ala instead of the
      canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1gamma is able to
      cleave at both downstream and upstream nsp1 junction sites. Although intermediate
      precursor polyproteins as well as alternative products generated by each of the
      SHFV PLP1s cleaving at sites within the N-terminal region of nsp1beta were
      produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell
      lysates with SHFV nsp1 protein-specific antibodies detected only the three mature
      nsp1 proteins. IMPORTANCE: SHFV is unique among arteriviruses in having three N
      terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or
      two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis
      of the products of in vitro autoprocessing of an N-terminal SHFV nonstructural 1a
      polypeptide fragment showed that each of the three SHFV PLP1s is active, and the
      predicted catalytic Cys residues and cleavage sites for each PLP1 were confirmed
      by testing mutant constructs. Several unique features of the SHFV PLP1s were
      discovered. The SHFV PLP1alpha catalytic Cys63 is unique among arterivirus PLP1s
      in being adjacent to an Ala instead of a Trp. Other arterivirus PLP1s cleave only
      in cis at a single downstream site, but SHFV PLP1gamma can cleave at both the
      downstream nsp1gamma-nsp2 and upstream nsp1beta-nsp1gamma junctions. The three
      mature nsp1 proteins were produced both in the in vitro reactions and in infected
      cells.

PMID- 24899182
TI  - Crucial roles of interleukin-7 in the development of T follicular helper cells
      and in the induction of humoral immunity.
AB  - T follicular helper (Tfh) cells are specialized providers of cognate B cell help,
      which is important in promoting the induction of high-affinity antibody
      production in germinal centers (GCs). Interleukin-6 (IL-6) and IL-21 have been
      known to play important roles in Tfh cell differentiation. Here, we demonstrate
      that IL-7 plays a pivotal role in Tfh generation and GC formation in vivo, as
      treatment with anti-IL-7 neutralizing antibody markedly impaired the development
      of Tfh cells and IgG responses. Moreover, codelivery of mouse Fc-fused IL-7 (IL-7
      mFc) with a vaccine enhanced the generation of GC B cells as well as Tfh cells
      but not other lineages of T helper cells, including Th1, Th2, and Th17 cells.
      Interestingly, a 6-fold-lower dose of an influenza virus vaccine codelivered with
      Fc-fused IL-7 induced higher antigen-specific and cross-reactive IgG titers than
      the vaccine alone in both mice and monkeys and led to markedly enhanced
      protection against heterologous influenza virus challenge in mice. Enhanced
      generation of Tfh cells by IL-7-mFc treatment was not significantly affected by
      the neutralization of IL-6 and IL-21, indicating an independent role of IL-7 on
      Tfh differentiation. Thus, IL-7 holds promise as a critical cytokine for
      selectively inducing Tfh cell generation and enhancing protective IgG responses.
      IMPORTANCE: Here, we demonstrate for the first time that codelivery of Fc-fused
      IL-7 significantly increased influenza virus vaccine-induced antibody responses,
      accompanied by robust expansion of Tfh cells and GC B cells as well as enhanced
      GC formation. Furthermore, IL-7-mFc induced earlier and cross-reactive IgG
      responses, leading to striking protection against heterologous influenza virus
      challenge. These results suggest that Fc-fused IL-7 could be used for inducing
      strong and cross-protective humoral immunity against highly mutable viruses, such
      as HIV and hepatitis C virus, as well as influenza viruses.

PMID- 24899185
TI  - Host species restriction of Middle East respiratory syndrome coronavirus through
      its receptor, dipeptidyl peptidase 4.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012.
      Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and
      the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike
      protein and DPP4 was determined by crystallography. Animal studies identified
      rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS
      CoV. Here, we investigated the role of DPP4 in this observed species tropism.
      Cell lines of human and nonhuman primate origin were permissive of MERS-CoV,
      whereas hamster, ferret, or mouse cell lines were not, despite the presence of
      DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled
      MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not.
      Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human
      (susceptible) or hamster (nonsusceptible) identified five amino acid residues
      involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the
      five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas
      expression of human DPP4 containing the five hamster DPP4 amino acids did not.
      Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common
      Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD
      interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat,
      cow, and sheep. Expression of the DPP4s of these species on BHK cells supported
      MERS-CoV replication. This suggests, together with the abundant DPP4 presence in
      the respiratory tract, that these species might be able to function as a MERS-CoV
      intermediate reservoir. IMPORTANCE: The ongoing outbreak of Middle East
      respiratory syndrome coronavirus (MERS-CoV) has caused 701 laboratory-confirmed
      cases to date, with 249 fatalities. Although bats and dromedary camels have been
      identified as potential MERS-CoV hosts, the virus has so far not been isolated
      from any species other than humans. The inability of MERS-CoV to infect commonly
      used animal models, such as hamster, mice, and ferrets, indicates the presence of
      a species barrier. We show that the MERS-CoV receptor DPP4 plays a pivotal role
      in the observed species tropism of MERS-CoV and subsequently identified the amino
      acids in DPP4 responsible for this restriction. Using a combined modeling and
      experimental approach, we predict that, based on the ability of MERS-CoV to
      utilize the DPP4 of common Middle East livestock species, such as camels, goats,
      sheep, and cows, these form a potential MERS-CoV intermediate host reservoir
      species.

PMID- 24899183
TI  - Maturation and vesicle-mediated egress of primate gammaherpesvirus rhesus monkey
      rhadinovirus require inner tegument protein ORF52.
AB  - The tegument layer of herpesviruses comprises a collection of proteins that is
      unique to each viral species. In rhesus monkey rhadinovirus (RRV), a close
      relative of the human oncogenic pathogen Kaposi's sarcoma-associated herpesvirus,
      ORF52 is a highly abundant tegument protein tightly associated with the capsid.
      We now report that ORF52 knockdown during RRV infection of rhesus fibroblasts led
      to a greater than 300-fold reduction in the viral titer by 48 h but had little
      effect on the number of released particles and caused only modest reductions in
      the levels of intracellular viral genomic DNA and no appreciable change in viral
      DNA packaging into capsids. These data suggested that the lack of ORF52 resulted
      in the production and release of defective particles. In support of this
      interpretation, transmission electron microscopy (TEM) revealed that without
      ORF52, capsid-like particles accumulated in the cytoplasm and were unable to
      enter egress vesicles, where final tegumentation and envelopment normally occur.
      TEM also demonstrated defective particles in the medium that closely resembled
      the accumulating intracellular particles, having neither a full tegument nor an
      envelope. The disruption in tegument formation from ORF52 suppression, therefore,
      prevented the incorporation of ORF45, restricting its subcellular localization to
      the nucleus and appearing, by confocal microscopy, to inhibit particle transport
      toward the periphery. Ectopic expression of small interfering RNA (siRNA)
      resistant ORF52 was able to partially rescue all of these phenotypic changes. In
      sum, our results indicate that efficient egress of maturing virions and, in
      agreement with studies on murine gammaherpesvirus 68 (MHV-68), complete
      tegumentation and secondary envelopment are dependent on intact ORF52.
      IMPORTANCE: The tegument, or middle layer, of herpesviruses comprises both viral
      and cellular proteins that play key roles in the viral life cycle. A subset of
      these proteins is present only within members of one of the three subfamilies
      (alphaherpesviruses, betaherpesviruses, or gammaherpesviruses) of Herpesviridae.
      In this report, we show that the gammaherpesvirus-specific tegument protein ORF52
      is critical for maturation of RRV, the closest relative of Kaposi's sarcoma
      associated herpesvirus (KSHV) (a human cancer-causing pathogen) that has
      undergone this type of analysis. Without ORF52, the nascent subviral particles
      are essentially stuck in maturation limbo, unable to acquire the tegument or
      outer (envelope) layers. This greatly attenuates infectivity. Our data, together
      with earlier work on a murine homolog, as well as a more distantly related human
      homolog, provide a more complete understanding of how early protein interactions
      involving virus-encoded tegument proteins are critical for virus assembly and are
      also, therefore, potentially attractive therapeutic targets.

PMID- 24899186
TI  - Infection and pathogenesis of canine, equine, and human influenza viruses in
      canine tracheas.
AB  - Influenza A viruses (IAVs) can jump species barriers and occasionally cause
      epidemics, epizootics, pandemics, and panzootics. Characterizing the infection
      dynamics at the target tissues of natural hosts is central to understanding the
      mechanisms that control host range, tropism, and virulence. Canine influenza
      virus (CIV; H3N8) originated after the transfer of an equine influenza virus
      (EIV) into dogs. Thus, comparing CIV and EIV isolates provides an opportunity to
      study the determinants of influenza virus emergence. Here we characterize the
      replication of canine, equine, and human IAVs in the trachea of the dog, a
      species to which humans are heavily exposed. We define a phenotype of infection
      for CIV, which is characterized by high levels of virus replication and extensive
      tissue damage. CIV was compared to evolutionarily distinct EIVs, and the early
      EIV isolates showed an impaired ability to infect dog tracheas, while EIVs that
      circulated near the time of CIV emergence exhibited a CIV-like infection
      phenotype. Inoculating dog tracheas with various human IAVs (hIAVs) showed that
      they infected the tracheal epithelium with various efficiencies depending on the
      virus tested. Finally, we show that reassortant viruses carrying gene segments of
      CIV and hIAV are viable and that addition of the hemagglutinin (HA) and
      neuraminidase (NA) of CIV to the 2009 human pandemic virus results in a virus
      that replicates at high levels and causes significant lesions. This provides
      important insights into the role of evolution on viral emergence and on the role
      of HA and NA as determinants of pathogenicity. IMPORTANCE: Influenza A viruses
      (IAVs) have entered new host species in recent history, sometimes with
      devastating consequences. Canine influenza virus (CIV) H3N8 originated from a
      direct transfer of an equine influenza virus (EIV) in the early 2000s. We studied
      the infection patterns of IAVs that circulate in dogs or to which dogs are
      commonly exposed and showed that CIV emergence was likely caused by an adaptive
      driver, as evolutionarily distinct EIVs display distinct infection phenotypes. We
      also showed that many human viruses can infect dog tracheas and that reassortment
      with CIV results in viable viruses. Finally, we showed that the hemagglutinin and
      neuraminidase of CIV act as virulence factors. Our findings have significant
      implications because they show that dogs might act as "mixing vessels" in which
      novel viruses with pandemic potential could emerge and also provide experimental
      evidence supporting the role of viral evolution in influenza virus emergence.

PMID- 24899187
TI  - The pulmonary localization of virus-specific T lymphocytes is governed by the
      tissue tropism of infection.
AB  - The migration of pathogen-specific T cells into nonlymphoid tissues, such as the
      lung, is critical to control peripheral infections. Use of in vivo intravascular
      labeling of leukocytes has allowed for improved discrimination between cells
      located in the blood from cells present within peripheral tissues, such as the
      lung. This is particularly important in the lung, which is comprised of an
      intricate network of blood vessels that harbors a large proportion of the total
      blood volume at any given time. Recent work has demonstrated that >80% of antigen
      specific effector CD8 T cells remain in the pulmonary vasculature following an
      intratracheal infection with a systemic viral pathogen. However, it remains
      unclear what proportion of effector CD8 T cells are located within lung tissue
      following a localized respiratory viral infection. We confirm that most effector
      and memory CD8 T cells are found in the vasculature after an intranasal infection
      with the systemic pathogens lymphocytic choriomeningitis virus (LCMV) or vaccinia
      virus (VACV). In contrast, following pulmonary viral infections with either
      respiratory syncytial virus (RSV) or influenza A virus (IAV), 80 to 90% of the
      antigen-specific effector CD8 T cells were located within lung tissue. Similarly,
      the majority of antigen-specific CD4 T cells were present within lung tissue
      during a pulmonary viral infection. Furthermore, a greater proportion of gamma
      interferon-positive (IFN-gamma(+)) effector CD8 and CD4 T cells were located
      within lung tissue following a localized respiratory viral infection. Our results
      indicate that T cells exhibit significantly altered distribution patterns
      dependent upon the tissue tropism of the infection. IMPORTANCE: The migration of
      T cells to nonlymphoid sites, such as the lung, is critical to mediate clearance
      of viral infections. The highly vascularized lung holds up to 40% of blood, and
      thus, the T cell response may be a reflection of lymphocytes localized to the
      pulmonary vasculature instead of lung tissue. We examined the localization of T
      cell responses within the lung following either a localized or systemic viral
      infection. We demonstrate that following intranasal infection with a systemic
      pathogen, most T cells are localized to the pulmonary vasculature. In contrast, T
      cells are primarily localized to lung tissue following a respiratory viral
      infection. Our results demonstrate vast differences in the localization of T cell
      responses within the lung parenchyma between pathogens that can replicate locally
      versus systemically and that intravascular antibody labeling can be utilized to
      assess the localization patterns of T cell responses in nonlymphoid organs.

PMID- 24899188
TI  - Disease severity is associated with differential gene expression at the early and
      late phases of infection in nonhuman primates infected with different H5N1 highly
      pathogenic avian influenza viruses.
AB  - Occasional transmission of highly pathogenic avian H5N1 influenza viruses to
      humans causes severe pneumonia with high mortality. To better understand the
      mechanisms via which H5N1 viruses induce severe disease in humans, we infected
      cynomolgus macaques with six different H5N1 strains isolated from human patients
      and compared their pathogenicity and the global host responses to the virus
      infection. Although all H5N1 viruses replicated in the respiratory tract, there
      was substantial heterogeneity in their replicative ability and in the disease
      severity induced, which ranged from asymptomatic to fatal. A comparison of global
      gene expression between severe and mild disease cases indicated that interferon
      induced upregulation of genes related to innate immunity, apoptosis, and antigen
      processing/presentation in the early phase of infection was limited in severe
      disease cases, although interferon expression was upregulated in both severe and
      mild cases. Furthermore, coexpression analysis of microarray data, which reveals
      the dynamics of host responses during the infection, demonstrated that the
      limited expression of these genes early in infection led to a failure to suppress
      virus replication and to the hyperinduction of genes related to immunity,
      inflammation, coagulation, and homeostasis in the late phase of infection,
      resulting in a more severe disease. Our data suggest that the attenuated
      interferon-induced activation of innate immunity, apoptosis, and antigen
      presentation in the early phase of H5N1 virus infection leads to subsequent
      severe disease outcome. IMPORTANCE: Highly pathogenic avian H5N1 influenza
      viruses sometimes transmit to humans and cause severe pneumonia with ca. 60%
      lethality. The continued circulation of these viruses poses a pandemic threat;
      however, their pathogenesis in mammals is not fully understood. We, therefore,
      investigated the pathogenicity of six H5N1 viruses and compared the host
      responses of cynomolgus macaques to the virus infection. We identified
      differences in the viral replicative ability of and in disease severity caused by
      these H5N1 viruses. A comparison of global host responses between severe and mild
      disease cases identified the limited upregulation of interferon-stimulated genes
      early in infection in severe cases. The dynamics of the host responses indicated
      that the limited response early in infection failed to suppress virus replication
      and led to hyperinduction of pathological condition-related genes late in
      infection. These findings provide insight into the pathogenesis of H5N1 viruses
      in mammals.

PMID- 24899189
TI  - Identification of human cytomegalovirus genes important for biogenesis of the
      cytoplasmic virion assembly complex.
AB  - Human cytomegalovirus (HCMV) has many effects on cells, including remodeling the
      cytoplasm to form the cytoplasmic virion assembly complex (cVAC), the site of
      final virion assembly. Viral tegument, envelope, and some nonstructural proteins
      localize to the cVAC, and cytoskeletal filaments radiate from a microtubule
      organizing center in the cVAC. The endoplasmic reticulum (ER)-to-Golgi
      intermediate compartment, Golgi apparatus, and trans-Golgi network form a ring
      that outlines the cVAC. The center of the cVAC ring is occupied by numerous
      vesicles that share properties with recycling endosomes. In prior studies, we
      described the three-dimensional structure and the extensive remodeling of the
      cytoplasm and shifts in organelle identity that occur during development of the
      cVAC. The objective of this work was to identify HCMV proteins that regulate cVAC
      biogenesis. Because the cVAC does not form in the absence of viral DNA synthesis,
      we employed HCMV-infected cells transfected with synthetic small interfering RNAs
      (siRNAs) that targeted 26 candidate early-late and late protein-coding genes
      required for efficient virus replication. We identified three HCMV genes (UL48,
      UL94, and UL103) whose silencing had major effects on cVAC development, including
      failure to form the Golgi ring and dispersal of markers of early and recycling
      endosomes. To confirm and extend the siRNA results, we constructed recombinant
      viruses in which pUL48 and pUL103 are fused with a regulatable protein
      destabilization domain (dd-FKBP). In the presence of a stabilizing ligand (Shield
      1), the cVAC appeared to develop normally. In its absence, cVAC development was
      abrogated, verifying roles for pUL48 and pUL103 in cVAC biogenesis. IMPORTANCE:
      Human cytomegalovirus (HCMV) is an important human pathogen that causes disease
      and disability in immunocompromised individuals and in children infected before
      birth. Few drugs are available for treatment of HCMV infections. HCMV remodels
      the interior of infected cells to build a factory for assembling new infectious
      particles (virions), the cytoplasmic virion assembly complex (cVAC). Here, we
      identified three HCMV genes (UL48, UL94, and UL103) as important contributors to
      cVAC development. In addition, we found that mutant viruses that express an
      unstable form of the UL103 protein have defects in cVAC development and
      production of infectious virions and produce small plaques and intracellular
      virions with aberrant appearances. Of these, only the reduced production of
      infectious virions is not eliminated by chemically stabilizing the protein. In
      addition to identifying new functions for these HCMV genes, this work is a
      necessary prelude to developing novel antivirals that would block cVAC
      development.

PMID- 24899190
TI  - Defining the chemokine basis for leukocyte recruitment during viral encephalitis.
AB  - The encephalitic response to viral infection requires local chemokine production
      and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly,
      chemokine receptors present themselves as plausible therapeutic targets for drugs
      aimed at limiting encephalitic responses. However, it remains unclear which
      chemokines are central to this process and whether leukocyte recruitment is
      important for limiting viral proliferation and survival in the brain or whether
      it is predominantly a driver of coincident inflammatory pathogenesis. Here we
      examine chemokine expression and leukocyte recruitment in the context of
      avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus
      infection and demonstrate rapid and robust expression of a variety of
      inflammatory CC and CXC chemokines in all models. On this basis, we define a
      chemokine axis involved in leukocyte recruitment to the encephalitic brain during
      SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and
      CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition
      of each of these receptors individually and the resulting suppression of
      leukocyte recruitment to the infected brain have no effect on viral titer or
      survival following infection with a virulent SFV strain. In contrast,
      simultaneous blockade of CXCR3 and CCR2 results in significantly reduced
      mortality in response to virulent SFV infection. In summary, therefore, our data
      provide an unprecedented level of insight into chemokine orchestration of
      leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and
      CCR2 as possible therapeutic targets for limiting inflammatory damage in response
      to viral infection of the brain. IMPORTANCE: Brain inflammation (encephalitis) in
      response to viral infection can lead to severe illness and even death. This
      therefore represents an important clinical problem and one that requires the
      development of new therapeutic approaches. Central to the pathogenesis of
      encephalitis is the recruitment of inflammatory leukocytes to the infected brain,
      a process driven by members of the chemokine family. Here we provide an in-depth
      analysis of the chemokines involved in leukocyte recruitment to the virally
      infected brain and demonstrate that simultaneous blockade of two of these
      receptors, namely, CXCR3 and CCR2, does not alter viral titers within the brain
      but markedly reduces inflammatory leukocyte recruitment and enhances survival in
      a murine model of lethal viral encephalitis. Our results therefore highlight
      chemokine receptors as plausible therapeutic targets in treating viral
      encephalitis.

PMID- 24899192
TI  - Western equine encephalitis virus: evolutionary analysis of a declining
      alphavirus based on complete genome sequences.
AB  - Western equine encephalitis virus (WEEV) is an arbovirus from the genus
      Alphavirus, family Togaviridae, which circulates in North America between birds
      and mosquitoes, occasionally causing disease in humans and equids. In recent
      decades, human infection has decreased dramatically; the last documented human
      case in North America occurred in 1994, and the virus has not been detected in
      mosquito pools since 2008. Because limited information exists regarding the
      evolution of WEEV, we analyzed the genomic sequences of 33 low-passage-number
      strains with diverse geographic and temporal distributions and performed
      comprehensive phylogenetic analyses. Our results indicated that WEEV is a highly
      conserved alphavirus with only approximately 5% divergence in its most variable
      genes. We confirmed the presence of the previously determined group A and B
      lineages and further resolved group B into three sublineages. We also observed an
      increase in relative genetic diversity during the mid-20th century, which
      correlates with the emergence and cocirculation of several group B sublineages.
      The estimated WEEV population size dropped in the 1990s, with only the group B3
      lineage being sampled in the past 20 years. Structural mapping showed that the
      majority of substitutions in the envelope glycoproteins occurred at the E2-E2
      interface. We hypothesize that an event occurred in the mid-20th century that
      resulted in the increased genetic diversity of WEEV in North America, followed by
      genetic constriction due to either competitive displacement by the B3 sublineage
      or stochastic events resulting from a population decline. IMPORTANCE: Western
      equine encephalitis virus (WEEV) has caused several epidemics that resulted in
      the deaths of thousands of humans and hundreds of thousands of equids during the
      past century. During recent decades, human infection decreased drastically and
      the virus has not been found in mosquito pools since 2008. Because limited
      information exists regarding the evolution of WEEV, we analyzed 33 complete
      genome sequences and conducted comprehensive phylogenetic analyses. We confirmed
      the presence of two major lineages, one of which diverged into three sublineages.
      Currently, only one of those sublineages is found circulating in nature.
      Understanding the evolution of WEEV over the past century provides a unique
      opportunity to observe an arbovirus that is in decline and to better understand
      what factors can cause said decline.

PMID- 24899191
TI  - HIV-1 Vpr redirects host ubiquitination pathway.
AB  - HIV-1 modulates key host cellular pathways for successful replication and
      pathogenesis through viral proteins. By evaluating the hijacking of the host
      ubiquitination pathway by HIV-1 at the whole-cell level, we now show major
      perturbations in the ubiquitinated pool of the host proteins post-HIV-1
      infection. Our overexpression- and infection-based studies of T cells with wild
      type and mutant HIV-1 proviral constructs showed that Vpr is necessary and
      sufficient for reducing whole-cell ubiquitination. Mutagenic analysis revealed
      that the three leucine-rich helical regions of Vpr are critical for this novel
      function of Vpr, which was independent of its other known cellular functions. We
      also validated that this effect of Vpr was conserved among different subtypes
      (subtypes B and C) and circulating recombinants from Northern India. Finally, we
      establish that this phenomenon is involved in HIV-1-mediated diversion of host
      ubiquitination machinery specifically toward the degradation of various
      restriction factors during viral pathogenesis. IMPORTANCE: HIV-1 is known to rely
      heavily on modulation of the host ubiquitin pathway, particularly for
      counteraction of antiretroviral restriction factors, i.e., APOBEC3G, UNG2, and
      BST-2, etc.; viral assembly; and release. Reports to date have focused on the
      molecular hijacking of the ubiquitin machinery by HIV-1 at the level of E3
      ligases. Interaction of a viral protein with an E3 ligase alters its specificity
      to bring about selective protein ubiquitination. However, in the case of
      infection, multiple viral proteins can interact with this multienzyme pathway at
      various levels, making it much more complicated. Here, we have addressed the
      manipulation of ubiquitination at the whole-cell level post-HIV-1 infection. Our
      results show that HIV-1 Vpr is necessary and sufficient to bring about the
      redirection of the host ubiquitin pathway toward HIV-1-specific outcomes. We also
      show that the three leucine-rich helical regions of Vpr are critical for this
      effect and that this ability of Vpr is conserved across circulating recombinants.
      Our work, the first of its kind, provides novel insight into the regulation of
      the ubiquitin system at the whole-cell level by HIV-1.

PMID- 24899194
TI  - Avian influenza H7N9/13 and H7N7/13: a comparative virulence study in chickens,
      pigeons, and ferrets.
AB  - Human influenza cases caused by a novel avian H7N9 virus in China emphasize the
      zoonotic potential of that subtype. We compared the infectivity and pathogenicity
      of the novel H7N9 virus with those of a recent European avian H7N7 strain in
      chickens, pigeons, and ferrets. Neither virus induced signs of disease despite
      substantial replication in inoculated chickens and rapid transmission to contact
      chickens. Evidence of the replication of both viruses in pigeons, albeit at lower
      levels of RNA excretion, was also detected. No clear-cut differences between the
      two H7 isolates emerged regarding replication and antibody development in avian
      hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than
      of the H7N7 strain was observed with significant differences in viral presence,
      e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses
      showed the potential to spread to the mammal brain. We conclude that efficient
      asymptomatic viral replication and shedding, as shown in chickens, facilitate the
      spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are
      required for the handling of poultry infected with avian influenza viruses of the
      H7 subtype, independently of their pathogenicity for gallinaceous poultry.
      IMPORTANCE: This study is important to the field since it provides data about the
      behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and
      ferrets in comparison with that of a recent low-pathogenicity H7N7 strain
      isolated from poultry. We clearly show that chickens, but not pigeons, are highly
      permissive hosts of both H7 viruses, allowing high-titer replication and virus
      shedding without any relevant clinical signs. In the ferret model, the potential
      of both viruses to infect mammals could be demonstrated, including infection of
      the brain. However, the replication efficiency of the H7N9 virus in ferrets was
      higher than that of the H7N7 strain. In conclusion, valuable data for the risk
      analysis of low-pathogenicity avian influenza viruses of the H7 subtype are
      provided that could also be used for the risk assessment of zoonotic potentials
      and necessary biosafety measures.

PMID- 24899195
TI  - An alphavirus-based adjuvant enhances serum and mucosal antibodies, T cells, and
      protective immunity to influenza virus in neonatal mice.
AB  - Neonatal immune responses to infection and vaccination are biased toward TH2 at
      the cost of proinflammatory TH1 responses needed to combat intracellular
      pathogens. However, upon appropriate stimulation, the neonatal immune system can
      induce adult-like TH1 responses. Here we report that a new class of vaccine
      adjuvant is especially well suited to enhance early life immunity. The GVI3000
      adjuvant is a safe, nonpropagating, truncated derivative of Venezuelan equine
      encephalitis virus that targets dendritic cells (DCs) in the draining lymph node
      (DLN) and produces intracellular viral RNA without propagating to other cells.
      RNA synthesis strongly activates the innate immune response so that in adult
      animals, codelivery of soluble protein antigens induces robust humoral, cellular,
      and mucosal responses. The adjuvant properties of GVI3000 were tested in a
      neonatal BALB/c mouse model using inactivated influenza virus (iFlu). After a
      single immunization, mice immunized with iFlu with the GVI3000 adjuvant (GVI3000
      adjuvanted iFlu) had significantly higher and sustained influenza virus-specific
      IgG antibodies, mainly IgG2a (TH1), compared to the mice immunized with antigen
      only. GVI3000 significantly increased antigen-specific CD4(+) and CD8(+) T cells,
      primed mucosal immune responses, and enhanced protection from lethal challenge.
      As seen in adult mice, the GVI3000 adjuvant increased the DC population in the
      DLNs, caused activation and maturation of DCs, and induced proinflammatory
      cytokines and chemokines in the DLNs soon after immunization, including gamma
      interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), granulocyte
      colony-stimulating factor (G-CSF), and interleukin 6 (IL-6). In summary, the
      GVI3000 adjuvant induced an adult-like adjuvant effect with an influenza vaccine
      and has the potential to improve the immunogenicity and protective efficacy of
      new and existing neonatal vaccines. IMPORTANCE: The suboptimal immune responses
      in early life constitute a significant challenge for vaccine design. Here we
      report that a new class of adjuvant is safe and effective for early life
      immunization and demonstrate its ability to significantly improve the protective
      efficacy of an inactivated influenza virus vaccine in a neonatal mouse model. The
      GVI3000 adjuvant delivers a truncated, self-replicating viral RNA into dendritic
      cells in the draining lymph node. Intracellular RNA replication activates a
      strong innate immune response that significantly enhances adaptive antibody and
      cellular immune responses to codelivered antigens. A significant increase in
      protection results from a single immunization. Importantly, this adjuvant also
      primed a mucosal IgA response, which is likely to be critical for protection
      during many early life infections.

PMID- 24899193
TI  - Transcriptional and posttranscriptional regulation of cytokine gene expression in
      HIV-1 antigen-specific CD8+ T cells that mediate virus inhibition.
AB  - The ability of CD8+ T cells to effectively limit HIV-1 replication and block HIV
      1 acquisition is determined by the capacity to rapidly respond to HIV-1 antigens.
      Understanding both the functional properties and regulation of an effective CD8+
      response would enable better evaluation of T cell-directed vaccine strategies and
      may inform the design of new therapies. We assessed the antigen specificity,
      cytokine signature, and mechanisms that regulate antiviral gene expression in
      CD8+ T cells from a cohort of HIV-1-infected virus controllers (VCs) (<5,000 HIV
      1 RNA copies/ml and CD4+ lymphocyte counts of >400 cells/MUl) capable of soluble
      inhibition of HIV-1. Gag p24 and Nef CD8+ T cell-specific soluble virus
      inhibition was common among the VCs and correlated with substantial increases in
      the abundance of mRNAs encoding the antiviral cytokines macrophage inflammatory
      proteins MIP-1alpha, MIP-1alphaP (CCL3L1), and MIP-1beta; granulocyte-macrophage
      colony-stimulating factor (GM-CSF); lymphotactin (XCL1); tumor necrosis factor
      receptor superfamily member 9 (TNFRSF9); and gamma interferon (IFN-gamma). The
      induction of several of these mRNAs was driven through a coordinated response of
      both increased transcription and stabilization of mRNA, which together accounted
      for the observed increase in mRNA abundance. This coordinated response allows
      rapid and robust induction of mRNA messages that can enhance the CD8+ T cells'
      ability to inhibit virus upon antigen encounter. IMPORTANCE: We show that mRNA
      stability, in addition to transcription, is key in regulating the direct anti-HIV
      1 function of antigen-specific memory CD8+ T cells. Regulation at the level of
      RNA helps enable rapid recall of memory CD8+ T cell effector functions for HIV-1
      inhibition. By uncovering and understanding the mechanisms employed by CD8+ T
      cell subsets with antigen-specific anti-HIV-1 activity, we can identify new
      strategies for comprehensive identification of other important antiviral genes.
      This will, in turn, enhance our ability to inhibit virus replication by informing
      both cure strategies and HIV-1 vaccine designs that aim to reduce transmission
      and can aid in blocking HIV-1 acquisition.

PMID- 24899196
TI  - Hepatitis C virus entry is impaired by claudin-1 downregulation in diacylglycerol
      acyltransferase-1-deficient cells.
AB  - Diacylglycerol acyltransferase-1 (DGAT1) is involved in the assembly of hepatitis
      C virus (HCV) by facilitating the trafficking of the HCV core protein to the
      lipid droplet. Here, we abrogated DGAT1 expression in Huh-7.5 cells by using
      either the transcription activator-like effector nuclease (TALEN) or lentivirus
      vector short hairpin RNA (shRNA) and achieved complete long-term silencing of
      DGAT1. HCV entry was severely impaired in DGAT1-silenced Huh-7.5 cell lines,
      which showed markedly diminished claudin-1 (CLDN1) expression. In DGAT1-silenced
      cell lines, the forced expression of CLDN1 restored HCV entry, implying that the
      downregulation of CLDN1 is a critical factor underlying defective HCV entry. The
      expression of the gene coding for hepatocyte nuclear factor 4alpha (HNF4alpha)
      and other hepatocyte-specific genes was also reduced in DGAT1-silenced cell
      lines. After DGAT1 gene rescue, CLDN1 expression was preserved, and HCV entry was
      restored. Strikingly, after DGAT1 silencing, CLDN1 expression and HCV entry were
      also restored by low-dose palmitic acid treatment, indicating that the
      downregulation of CLDN1 was associated with altered fatty acid homeostasis in the
      absence of DGAT1. Our findings provide novel insight into the role of DGAT1 in
      the life cycle of HCV. IMPORTANCE: In this study, we report the novel effect of
      complete silencing of DGAT1 on the entry of HCV. DGAT1 was recently reported as a
      host factor of HCV, involved in the assembly of HCV by facilitating the
      trafficking of the HCV core protein to lipid droplets. We achieved complete and
      long-term silencing of DGAT1 by either TALEN or repeated transduction of
      lentivirus shRNA. We found that HCV entry was severely impaired in DGAT1-silenced
      cell lines. The impairment of HCV entry was caused by CLDN1 downregulation, and
      the expression of HNF4alpha and other hepatocyte-specific genes was also
      downregulated in DGAT1-silenced cell lines. Our results suggest new roles of
      DGAT1 in human liver-derived cells: maintaining intracellular lipid homeostasis
      and affecting HCV entry by modulating CLDN1 expression.

PMID- 24899197
TI  - Asthma increases susceptibility to heterologous but not homologous secondary
      influenza.
AB  - Asthma was the most common comorbidity observed among patients hospitalized with
      influenza A virus during the 2009 pandemic. However, little remains known about
      how the asthmatic phenotype influences protective immune responses against
      respiratory viral pathogens. Using the ovalbumin-induced allergic lung
      inflammation model, we found that asthmatic mice, unlike nonasthmatic mice, were
      highly susceptible to secondary heterologous virus challenge. While primary virus
      infection generated protective memory immune responses against homologous
      secondary virus challenge in both asthmatic and nonasthmatic mice, full
      protection against heterologous A/California/04/2009 (CA04) viral infection was
      observed only in nonasthmatic mice. Significant reductions in CA04-specific IgA,
      IgG, and IgM levels and in CA04-neutralizing activity of bronchoalveolar lavage
      fluid (BALF) was observed following secondary CA04 challenge of PR8-immunized
      asthmatic mice. Furthermore, transfer of immune BALF obtained from nonasthmatic,
      but not asthmatic, donors following secondary viral infection generated
      protection against CA04 in naive recipients. Nonspecific B-cell activation by CpG
      inoculation restored protection in PR8-immunized, CA04-challenged asthmatic mice.
      These results demonstrate a causal link between defective mucosal antibody
      responses and the heightened susceptibility of asthmatic mice to influenza
      infection and provide a mechanistic explanation for the observation that asthma
      was a major risk factor during the 2009 influenza pandemic. IMPORTANCE: The
      prevalence of asthma worldwide is increasing each year. Unfortunately, there is
      no cure for asthma. Asthmatic individuals not only suffer from consistent
      wheezing and coughing but are also believed to be more prone to serious lung
      infections that result in bronchitis and pneumonia. However, little is known
      about the influence of asthma on host mucosal immunity. Here we show that
      antibody responses during secondary heterologous influenza infections are
      suboptimal and that this is responsible for the increased mortality in asthmatic
      mice from viral infections. Understanding the mechanism of increased
      susceptibility will aid in developing new antiviral therapies for asthmatic
      patients.

PMID- 24899198
TI  - ISG15 functions as an interferon-mediated antiviral effector early in the murine
      norovirus life cycle.
AB  - Human noroviruses (HuNoV) are the leading cause of nonbacterial gastroenteritis
      worldwide. Similar to HuNoV, murine noroviruses (MNV) are enteric pathogens
      spread via the fecal-oral route and have been isolated from numerous mouse
      facilities worldwide. Type I and type II interferons (IFN) restrict MNV-1
      replication; however, the antiviral effectors impacting MNV-1 downstream of IFN
      signaling are largely unknown. Studies using dendritic cells, macrophages, and
      mice deficient in free and conjugated forms of interferon-stimulated gene 15
      (ISG15) revealed that ISG15 conjugation contributes to protection against MNV-1
      both in vitro and in vivo. ISG15 inhibited a step early in the viral life cycle
      upstream of viral genome transcription. Directly transfecting MNV-1 RNA into IFN
      stimulated mouse embryonic fibroblasts (MEFs) and bone marrow-derived dendritic
      cells (BMDC) lacking ISG15 conjugates bypassed the antiviral activity of ISG15,
      further suggesting that ISG15 conjugates restrict the MNV-1 life cycle at the
      viral entry/uncoating step. These results identify ISG15 as the first type I IFN
      effector regulating MNV-1 infection both in vitro and in vivo and for the first
      time implicate the ISG15 pathway in the regulation of early stages of MNV-1
      replication. IMPORTANCE: Type I IFNs are important in controlling murine
      norovirus 1 (MNV-1) infections; however, the proteins induced by IFNs that
      restrict viral growth are largely unknown. This report reveals that interferon
      stimulated gene 15 (ISG15) mitigates MNV-1 replication both in vitro and in vivo.
      In addition, it shows that ISG15 inhibits MNV-1 replication by targeting an early
      step in the viral life cycle, MNV-1 entry and/or uncoating. These results
      identify ISG15 as the first type I IFN effector regulating MNV-1 infection both
      in vitro and in vivo and for the first time implicate the ISG15 pathway in the
      regulation of viral entry/uncoating.

PMID- 24899199
TI  - Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that
      confer resistance to nonnucleoside reverse transcriptase and integrase strand
      transfer inhibitors.
AB  - Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) and integrase (IN)
      strand transfer inhibitors (INSTI) are key components of antiretroviral regimens.
      To explore potential interactions between NNRTI and INSTI resistance mutations,
      we investigated the combined effects of these mutations on drug susceptibility
      and fitness of human immunodeficiency virus type 1 (HIV-1). In the absence of
      drug, single-mutant viruses were less fit than the wild type; viruses carrying
      multiple mutations were less fit than single-mutant viruses. These findings were
      explained in part by the observation that mutant viruses carrying NNRTI plus
      INSTI resistance mutations had reduced amounts of virion-associated RT and/or IN
      protein. In the presence of efavirenz (EFV), a virus carrying RT-K103N together
      with IN-G140S and IN-Q148H (here termed IN-G140S/Q148H) mutations was fitter than
      a virus with a RT-K103N mutation alone. Similarly, in the presence of EFV, the RT
      E138K plus IN-G140S/Q148H mutant virus was fitter than one with the RT-E138K
      mutation alone. No effect of INSTI resistance mutations on the fitness of RT
      Y181C mutant viruses was observed. Conversely, RT-E138K and -Y181C mutations
      improved the fitness of the IN-G140S/Q148H mutant virus in the presence of
      raltegravir (RAL); the RT-K103N mutation had no effect. The NNRTI resistance
      mutations had no effect on RAL susceptibility. Likewise, the IN-G140S/Q148H
      mutations had no effect on EFV or RPV susceptibility. However, both the RT-K103N
      plus IN-G140S/Q148H and the RT-E138K plus IN-G140S/Q148H mutant viruses had
      significantly greater fold increases in 50% inhibitory concentration (IC50) of
      EFV than viruses carrying a single NNRTI mutation. Likewise, the RT-E138K plus IN
      G140S/Q148H mutant virus had significantly greater fold increases in RAL IC50
      than that of the IN-G140S/Q148H mutant virus. These results suggest that
      interactions between RT and IN mutations are important for NNRTI and INSTI
      resistance and viral fitness. IMPORTANCE: Nonnucleoside reverse transcriptase
      inhibitors and integrase inhibitors are used to treat infection with HIV-1.
      Mutations that confer resistance to these drugs reduce the ability of HIV-1 to
      reproduce (that is, they decrease viral fitness). It is known that reverse
      transcriptase and integrase interact and that some mutations can disrupt their
      interaction, which is necessary for proper functioning of these two enzymes. To
      determine whether resistance mutations in these enzymes interact, we investigated
      their effects on drug sensitivity and viral fitness. Although individual drug
      resistance mutations usually reduced viral fitness, certain combinations of
      mutations increased fitness. When present in certain combinations, some integrase
      inhibitor resistance mutations increased resistance to nonnucleoside reverse
      transcriptase inhibitors and vice versa. Because these drugs are sometimes used
      together in the treatment of HIV-1 infection, these interactions could make
      viruses more resistant to both drugs, further limiting their clinical benefit.

PMID- 24899200
TI  - Isolation and characterization of the DNA and protein binding activities of
      adenovirus core protein V.
AB  - The structure of adenovirus outer capsid was revealed recently at 3- to 4-A
      resolution (V. Reddy, S. Natchiar, P. Stewart, and G. Nemerow, Science 329:1071
      1075, 2010, http://dx.doi.org/10.1126/science.1187292); however, precise details
      on the function and biochemical and structural features for the inner core still
      are lacking. Protein V is one the most important components of the adenovirus
      core, as it links the outer capsid via association with protein VI with the inner
      DNA core. Protein V is a highly basic protein that strongly binds to DNA in a
      nonspecific manner. We report the expression of a soluble protein V that exists
      in monomer-dimer equilibrium. Using reversible cross-linking affinity
      purification in combination with mass spectrometry, we found that protein V
      contains multiple DNA binding sites. The binding sites from protein V mediate
      heat-stable nucleic acid associations, with some of the binding sites possibly
      masked in the virus by other core proteins. We also demonstrate direct
      interaction between soluble proteins V and VI, thereby revealing the bridging of
      the inner DNA core with the outer capsid proteins. These findings are consistent
      with a model of nucleosome-like structures proposed for the adenovirus core and
      encapsidated DNA. They also suggest an additional role for protein V in linking
      the inner nucleic acid core with protein VI on the inner capsid shell.
      IMPORTANCE: Scant knowledge exists of how the inner core of adenovirus containing
      its double-stranded DNA (dsDNA) genome and associated proteins is organized.
      Here, we report a purification scheme for a recombinant form of protein V that
      allowed analysis of its interactions with the nucleic acid core region. We
      demonstrate that protein V exhibits stable associations with dsDNA due to the
      presence of multiple nucleic acid binding sites identified both in the isolated
      recombinant protein and in virus particles. As protein V also binds to the
      membrane lytic protein VI molecules, this core protein may serve as a bridge from
      the inner dsDNA core to the inner capsid shell.

PMID- 24899201
TI  - Oncolytic activity of avian influenza virus in human pancreatic ductal
      adenocarcinoma cell lines.
AB  - Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer,
      with dismal survival rates due to late-stage diagnoses and a lack of efficacious
      therapies. Building on the observation that avian influenza A viruses (IAVs) have
      a tropism for the pancreas in vivo, the present study was aimed at testing the
      efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor
      characterization confirmed that human PDA cell lines express the alpha-2,3- and
      the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA
      cell lines were sensitive to infection by human and avian IAV isolates, which is
      consistent with this finding. Growth kinetic experiments showed preferential
      virus replication in PDA cells over that in a nontransformed pancreatic ductal
      cell line. Finally, at early time points posttreatment, infection with IAVs
      caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin,
      which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell
      line, apoptosis resulted from the engagement of the intrinsic mitochondrial
      pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic
      ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a
      xenograft in SCID mice, we also show that a slightly pathogenic avian IAV
      significantly inhibited tumor growth following intratumoral injection. Taken
      together, these results are the first to suggest that IAVs may hold promise as
      future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas.
      IMPORTANCE: Despite intensive studies aimed at designing new therapeutic
      approaches, PDA still retains the most dismal prognosis among human cancers. In
      the present study, we provide the first evidence indicating that avian IAVs of
      low pathogenicity display a tropism for human PDA cells, resulting in viral RNA
      replication and a potent induction of apoptosis in vitro and antitumor effects in
      vivo. These results suggest that slightly pathogenic IAVs may prove to be
      effective for oncolytic virotherapy of PDA and provide grounds for further
      studies to develop specific and targeted viruses, with the aim of testing their
      efficacy in clinical contexts.

PMID- 24899203
TI  - PB2 mutations D701N and S714R promote adaptation of an influenza H5N1 virus to a
      mammalian host.
AB  - Mutation D701N in the PB2 protein is known to play a prominent role in the
      adaptation of avian influenza A viruses to mammalian hosts. In contrast, little
      is known about the nearby mutations S714I and S714R, which have been observed in
      some avian influenza viruses highly pathogenic for mammals. We have generated
      recombinant H5N1 viruses with PB2 displaying the avian signature 701D or the
      mammalian signature 701N and serine, isoleucine, and arginine at position 714 and
      compared them for polymerase activity and virus growth in avian and mammalian
      cells, as well as for pathogenicity in mice. Mutation D701N led to an increase in
      polymerase activity and replication efficiency in mammalian cells and in mouse
      pathogenicity, and this increase was significantly enhanced when mutation D701N
      was combined with mutation S714R. Stimulation by mutation S714I was less
      distinct. These observations indicate that PB2 mutation S714R, in combination
      with the mammalian signature at position 701, has the potential to promote the
      adaptation of an H5N1 virus to a mammalian host. IMPORTANCE: Influenza A/H5N1
      viruses are avian pathogens that have pandemic potential, since they are spread
      over large parts of Asia, Africa, and Europe and are occasionally transmitted to
      humans. It is therefore of high scientific interest to understand the mechanisms
      that determine the host specificity and pathogenicity of these viruses. It is
      well known that the PB2 subunit of the viral polymerase is an important host
      range determinant and that PB2 mutation D701N plays an important role in virus
      adaptation to mammalian cells. In the present study, we show that mutation S714R
      is also involved in adaptation and that it cooperates with D701N in exposing a
      nuclear localization signal that mediates importin-alpha binding and entry of PB2
      into the nucleus, where virus replication and transcription take place.

PMID- 24899202
TI  - Identification of B cells as a major site for cyprinid herpesvirus 3 latency.
AB  - Cyprinid herpesvirus 3 (CyHV-3), commonly known as koi herpesvirus (KHV), is a
      member of the Alloherpesviridae, and is a recently discovered emerging
      herpesvirus that is highly pathogenic for koi and common carp. Our previous study
      demonstrated that CyHV-3 becomes latent in peripheral white blood cells (WBC). In
      this study, CyHV-3 latency was further investigated in IgM(+) WBC. The presence
      of the CyHV-3 genome in IgM(+) WBC was about 20-fold greater than in IgM(-) WBC.
      To determine whether CyHV-3 expressed genes during latency, transcription from
      all eight open reading frames (ORFs) in the terminal repeat was investigated in
      IgM(+) WBC from koi with latent CyHV-3 infection. Only a spliced ORF6 transcript
      was found to be abundantly expressed in IgM(+) WBC from CyHV-3 latently infected
      koi. The spliced ORF6 transcript was also detected in vitro during productive
      infection as early as 1 day postinfection. The ORF6 transcript from in vitro
      infection begins at -127 bp upstream of the ATG codon and ends +188 bp downstream
      of the stop codon, +20 bp downstream of the polyadenylation signal. The
      hypothetical protein of ORF6 contains a consensus sequence with homology to a
      conserved domain of EBNA-3B and ICP4 from Epstein-Barr virus and herpes simplex
      virus 1, respectively, both members of the Herpesviridae. This is the first
      report of latent CyHV-3 in B cells and identification of gene transcription
      during latency for a member of the Alloherpesviridae. IMPORTANCE: This is the
      first demonstration that a member of the Alloherpesviridae, cyprinid herpesvirus
      3 (CyHV-3), establishes a latent infection in the B cells of its host, Cyprinus
      carpio. In addition, this is the first report of identification of gene
      transcription during latency for a member of Herpesvirales outside Herpesviridae.
      This is also the first report that the hypothetical protein of latent transcript
      of CyHV-3 contains a consensus sequence with homology to a conserved domain of
      EBNA-3B from Epstein-Barr virus and ICP4 from herpes simplex virus 1, which are
      genes important for latency. These strongly suggest that latency is evolutionally
      conserved across vertebrates.

PMID- 24899206
TI  - Epithelial immunization induces polyfunctional CD8+ T cells and optimal mousepox
      protection.
AB  - We assessed several routes of immunization with vaccinia virus (VACV) in
      protecting mice against ectromelia virus (ECTV). By a wide margin, skin
      scarification provided the greatest protection. Humoral immunity and resident
      memory T cells notwithstanding, several approaches revealed that circulating,
      memory CD8(+) T cells primed via scarification were functionally superior and
      conferred enhanced virus control. Immunization via the epithelial route warrants
      further investigation, as it may also provide enhanced defense against other
      infectious agents. 

PMID- 24899207
TI  - Significant improvements in CO2 capture by pyridine-containing anion
      functionalized ionic liquids through multiple-site cooperative interactions.
AB  - A strategy for improving CO2 capture by new anion-functionalized ionic liquids
      (ILs) making use of multiple site cooperative interactions is reported. An
      extremely high capacity of up to 1.60 mol CO2 per mol IL and excellent
      reversibility were achieved by introducing a nitrogen-based interacting site on
      the phenolate and imidazolate anion. Quantum-chemical calculations, spectroscopic
      investigations, and calorimetric data demonstrated that multiple-site cooperative
      interactions between two kinds of interacting sites in the anion and CO2 resulted
      in superior CO2 capacities, which originated from the pi-electron delocalization
      in the pyridine ring. 

PMID- 24899204
TI  - Limited dissemination and shedding of the UL128 complex-intact, UL/b'-defective
      rhesus cytomegalovirus strain 180.92.
AB  - The UL128 complex of human cytomegalovirus (CMV) is a major determinant of viral
      entry into epithelial and endothelial cells and a target for vaccine development.
      The UL/b' region of rhesus CMV contains several open reading frames, including
      orthologs of the UL128 complex. We recently showed that the coding content of the
      rhesus CMV (RhCMV) UL/b' region predicts acute endothelial tropism and long-term
      shedding in vivo in the rhesus macaque model of CMV infection. The laboratory
      passaged RhCMV 180.92 strain has a truncated UL/b' region but an intact UL128
      complex. To investigate whether the presence of the UL128 complex alone was
      sufficient to confer endothelial and epithelial tropism in vivo, we investigated
      tissue dissemination and viral excretion following experimental RhCMV 180.92
      inoculation of RhCMV-seronegative rhesus macaques. We show the presence of at
      least two virus variants in the RhCMV 180.92 infectious virus stock. A rare
      variant noted for a nontruncated wild-type-virus-like UL/b' region, rapidly
      emerged during in vivo replication and showed high-level replication in blood and
      tissues and excretion in urine and saliva, features similar to those previously
      reported in naturally occurring wild-type RhCMV infection. In contrast, the
      predominant truncated version of RhCMV 180.92 showed significantly lower plasma
      DNAemia and limited tissue dissemination and viral shedding. These data
      demonstrate that the truncated RhCMV 180.92 variant is attenuated in vivo and
      suggest that additional UL/b' genes, besides the UL128 complex, are required for
      optimal in vivo CMV replication and dissemination. IMPORTANCE: An effective
      vaccine against human CMV infection will need to target genes that are essential
      for virus propagation and transmission. The human CMV UL128 complex represents
      one such candidate antigen since it is essential for endothelial and epithelial
      cell tropism, and is a target for neutralizing antibodies in CMV-infected
      individuals. In this study, we used the rhesus macaque animal model of CMV
      infection to investigate the in vivo function of the UL128 complex. Using
      experimental infection of rhesus macaques with a rhesus CMV virus variant that
      contained an intact UL128 complex but was missing several other genes, we show
      that the presence of the UL128 complex alone is not sufficient for widespread
      tissue dissemination and virus excretion. These data highlight the importance of
      in vivo studies in evaluating human CMV gene function and suggest that additional
      UL/b' genes are required for optimal CMV dissemination and transmission.

PMID- 24899209
TI  - The churn.

PMID- 24899208
TI  - Five reasons radiologists should embrace clinical decision support for diagnostic
      imaging.

PMID- 24899205
TI  - Kaposi's sarcoma-associated herpesvirus K3 and K5 ubiquitin E3 ligases have stage
      specific immune evasion roles during lytic replication.
AB  - The downregulation of immune synapse components such as major histocompatibility
      complex class I (MHC-I) and ICAM-1 is a common viral immune evasion strategy that
      protects infected cells from targeted elimination by cytolytic effector functions
      of the immune system. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two
      membrane-bound ubiquitin E3 ligases, called K3 and K5, which share the ability to
      induce internalization and degradation of MHC-I molecules. Although individual
      functions of K3 and K5 outside the viral genome are well characterized, their
      roles during the KSHV life cycle are still unclear. In this study, we
      individually introduced the amino acid-coding sequences of K3 or K5 into a
      DeltaK3 DeltaK5 recombinant virus, at either original or interchanged genomic
      positions. Recombinants harboring coding sequences within the K5 locus showed
      higher K3 and K5 protein expression levels and more rapid surface receptor
      downregulation than cognate recombinants in which coding sequences were
      introduced into the K3 locus. To identify infected cells undergoing K3-mediated
      downregulation of MHC-I, we employed a novel reporter virus, called red-green
      blue-BAC16 (RGB-BAC16), which was engineered to harbor three fluorescent protein
      expression cassettes: EF1alpha-monomeric red fluorescent protein 1 (mRFP1),
      polyadenylated nuclear RNA promoter (pPAN)-enhanced green fluorescent protein
      (EGFP), and pK8.1-monomeric blue fluorescent protein (tagBFP), marking latent,
      immediate early, and late viral gene expression, respectively. Analysis of RGB
      derived K3 and K5 deletion mutants showed that while the K5-mediated
      downregulation of MHC-I was concomitant with pPAN induction, the reduction of MHC
      I surface expression by K3 was evident in cells that were enriched for pPAN
      driven EGFP(high) and pK8.1-driven blue fluorescent protein-positive (BFP(+))
      populations. These data support the notion that immunoreceptor downregulation
      occurs by a sequential process wherein K5 is critical during the immediately
      early phase and K3 plays a significant role during later stages. IMPORTANCE:
      Although the roles of K3 and K5 outside the viral genome are well characterized,
      the function of these proteins in the context of the KSHV life cycle has remained
      unclear, particularly in the case of K3. This study examined the relative
      contributions of K3 and K5 to the downregulation of MHC-I during the lytic
      replication of KSHV. We show that while K5 acts immediately upon entry into the
      lytic phase, K3-mediated downregulation of MHC-I was evident during later stages
      of lytic replication. The identification of distinctly timed K3 and K5 activities
      significantly advances our understanding of KSHV-mediated immune evasion. Crucial
      to this study was the development of a novel recombinant KSHV, called RGB-BAC16,
      which facilitated the delineation of stage-specific phenotypes.

PMID- 24899210
TI  - Basics of finance and accounting.

PMID- 24899211
TI  - Emergency department imaging: uncompensated services rendered by radiologists
      nationwide.
AB  - PURPOSE: The aim of this study was to examine characteristics of uncompensated
      services rendered by radiologists to emergency department (ED) patients. METHODS:
      Using deidentified billing claims for 2,935 radiologists from 40 states from 2009
      through 2012, 18,475,491 services rendered to ED patients were identified.
      Analysis focused on the 133 of 830 procedure codes that comprised 99.0%
      (18,296,734) of all rendered services. The frequency, magnitude, and other
      characteristics of uncompensated (defined as zero payment) radiologist services
      were analyzed. National 2012 Medicare Physician Fee Schedule amounts were used to
      estimate service dollar values. RESULTS: Of 2,935 radiologists, 2,835 (96.6%)
      provided uncompensated care to ED patients, averaging $2,584 in professional
      services per physician per service month. Radiologists received no compensation
      at all for 28.4% of services (5,194,732 of 18,296,734). Just 8 procedure codes
      describing various chest, foot, and ankle radiographic and brain, abdominal and
      pelvic, and cervical spine CT examinations accounted for 51.0% of all imaging
      services rendered to ED patients. CT represented 31.2% of all services but
      accounted for 64.8% of uncompensated dollars. Although the uninsured received
      only 15.8% of all services, they accounted for 52.3% of all uncompensated
      services (2,714,506). CONCLUSION: More than 28% of services rendered by
      radiologists to ED patients are uncompensated, corresponding to $2,584 per month
      per physician. That frequency and magnitude could have patient access
      implications.

PMID- 24899212
TI  - A national drug related problems database: evaluation of use in practice,
      reliability and reproducibility.
AB  - BACKGROUND: A drug related problems database (DRP-database) was developed on
      request by clinical pharmacists. The information from the DRP-database has only
      been used locally e.g. to identify focus areas and to communicate identified DRPs
      to the hospital wards. Hence the quality of the data at the national level is
      unknown, which may compromise national analyses for benchmarking and
      identification of national focus areas. OBJECTIVE: The aim of the study was to
      evaluate the use in practice, reliability and reproducibility of the DRPs
      documented in the Danish drug related problems database. SETTING: Danish hospital
      pharmacies. METHODS: Practice use of the DRP-database was explored by an
      electronic questionnaire distributed to hospital pharmacies, and consisted of
      questions regarding current and previous use of the DRP-database. The reliability
      was evaluated by comparing the categorization of 24 cases by clinical pharmacists
      with categorization performed by the project group. Reproducibility was explored
      by re-categorization of a sample of existing records in the DRP-database by two
      project group members individually. MAIN OUTCOME MEASURES: Observed proportion of
      agreement and Fleiss' kappa as measures of inter-rater reliability and
      reproducibility. RESULTS: The practice use study of 12 hospital pharmacy
      locations revealed that when implementing the DRP-database, the majority of
      identified DRPs are documented in the DRP-database, however, some variations
      throughout the country exist. The interrater reliability study of 34 clinical
      pharmacists showed high inter-rater reliability with the project group (Fleiss'
      kappa = 0.79 with 95 % CI (0.70; 0.88)), and the reproducibility study also
      documented high inter-rater reliability of a sample of 379 records from the DRP
      database re-categorized by two project group members (Fleiss' kappa = 0.81 with
      95 % CI (0.78; 0.85)). CONCLUSION: The study showed high reliability and
      reproducibility of the DRP-database, however, some local variation in the use of
      the DRP-database throughout the country existed affecting the overall quality.
      These findings indicate that data in the DRP-database may be pooled, and national
      analyses may be conducted to explore development areas for common interest.

PMID- 24899213
TI  - A qualitative study of pharmacists' perceptions of, and recommendations for
      improvement of antibiotic use in Qatar.
AB  - BACKGROUND: Use of antibiotics has been correlated with increasing rates of
      resistance. Pharmacists are ideally positioned as front line health care
      providers to limit indiscriminate antibiotic use and promote the safe and
      effective administration of these medications. OBJECTIVE: The aim of this project
      was to assess pharmacists' opinions relating to antibiotic utilization in the
      community setting. SETTING: Doha, Qatar. METHOD: Community and primary care
      pharmacists were invited to participate in one of three focus groups or a semi
      structured interview at Qatar University or at their site of employment. A total
      of 22 community and primary care pharmacists participated in this study.
      Interviews were facilitated using a focus group guide, were recorded, and later
      transcribed. Transcripts were reviewed for recurring themes and coded using Nvivo
      software for qualitative research. MAIN OUTCOME MEASURE: Pharmacists'
      perceptions. RESULTS: Five major themes emerged from a series of focus groups and
      interviews. Themes which recurred across interview groups included:
      misconceptions and inappropriate practices by patients and healthcare providers,
      currently implemented strategies, perceived barriers, ways to overcome perceived
      barriers, and targets for improvement of antibiotic use in Qatar. The greatest
      need, as identified by pharmacists in this study was increased knowledge of the
      general population about appropriate antibiotic use through various educational
      interventions. CONCLUSION: Pharmacists report a number of misconceptions and
      inappropriate practices relating to antibiotic use in Qatar by patients and
      healthcare providers. Education to improve knowledge of appropriate antibiotic
      use is needed. Despite recognition of these issues, barriers are preventing
      pharmacists from implementing strategies to improve antibiotic use in Qatar.

PMID- 24899214
TI  - Joint spatial modeling to identify shared patterns among chronic related
      potentially preventable hospitalizations.
AB  - BACKGROUND: Rates of Potentially Preventable Hospitalizations (PPH) are used to
      evaluate access of territorially delimited populations to high quality ambulatory
      care. A common geographic pattern of several PPH would reflect the performance of
      healthcare providers. This study is aimed at modeling jointly the geographical
      variation in six chronic PPH conditions in one Spanish Autonomous Community for
      describing common and discrepant patterns, and to assess the relative weight of
      the common pattern on each condition. METHODS: Data on the 39,970 PPH hospital
      admissions for diabetes short term complications, chronic obstructive pulmonary
      disease (COPD), congestive heart failure, dehydration, angina admission and adult
      asthma, between 2007 and 2009 were extracted from the Hospital Discharge
      Administrative Databases and assigned to one of the 240 Basic Health Zones. Rates
      and Standardized Hospitalization Ratios per geographic unit were estimated. The
      spatial analysis was carried out jointly for PPH conditions using Shared
      Component Models (SCM). RESULTS: The component shared by the six PPH conditions
      explained about the 36% of the variability of each PPH condition, ranging from
      the 25.9 for dehydration to 58.7 for COPD. The geographical pattern found in the
      latent common component identifies territorial clusters with particularly high
      risk. The specific risk pattern that each isolated PPH does not share with the
      common pattern for all six conditions show many non-significant areas for most
      PPH, but with some exceptions. CONCLUSIONS: The geographical distribution of the
      risk of the PPH conditions is captured in a 36% by a unique latent pattern. The
      SCM modeling may be useful to evaluate healthcare system performance.

PMID- 24899215
TI  - Self-focused attention in anorexia nervosa.
AB  - OBJECTIVE: The clinical presentation of anorexia nervosa (AN) is characterized by
      preoccupation with body experience, intrusive concerns regarding shape, and
      pathological fears of weight gain. These symptoms are suggestive of unrelenting
      self-focused attention. No research to date has characterized self-focused
      attention (SFA) in AN nor examined neurocognitive features that may facilitate an
      excessive, rigid, or sustained focus on one's appearance. METHOD: This study
      examined SFA, body image disturbance, and executive functioning in women with
      current anorexia nervosa (AN-C; n = 24), a history of AN who were weight-restored
      at the time of the study (WR; n = 19), and healthy controls (n = 24). RESULTS:
      Private and public SFA were highest among WR and lowest among AN-C. Shape
      concerns were negatively correlated with SFA, especially among AN-C, after
      controlling for depression and social anxiety symptoms. DISCUSSION: Lower levels
      of SFA among AN-C were unexpected and suggest the acute state of AN may lessen
      pathological self-focus, negatively reinforcing symptoms. In addition, body image
      concerns may distract from general SFA. Deficits in executive attention may
      explain these findings, as each one unit increase in perseverative errors among
      AN-C participants was associated with an almost one-half unit decrease in public
      SFA.

PMID- 24899216
TI  - Rapid amplification/detection of nucleic acid targets utilizing a HDA/thin film
      biosensor.
AB  - Thin film biosensors exploit a flat, optically coated silicon-based surface
      whereupon formation of nucleic acid hybrids are enzymatically transduced in a
      molecular thin film that can be detected by the unaided human eye under white
      light. While the limit of sensitivity for detection of nucleic acid targets is at
      sub-attomole levels (60 000 copies) many clinical specimens containing bacterial
      pathogens have much lower levels of analyte present. Herein, we describe a
      platform, termed HDA/thin film biosensor, which performs helicase-dependant
      nucleic acid amplification on a thin film biosensor surface to improve the limit
      of sensitivity to 10 copies of the mecA gene present in methicillin-resistant
      strains of Staphylococcus. As double-stranded DNA is unwound by helicase it was
      either bound by solution-phase DNA primers to be copied by DNA polymerase or
      hybridized to surface immobilized probe on the thin film biosensor surface to be
      detected. Herein, we show that amplification reactions on the thin film biosensor
      are equivalent to in standard thin wall tubes, with detection at the limit of
      sensitivity of the assay occurring after 30 minutes of incubation time. Further
      we validate the approach by detecting the presence of the mecA gene in
      methicillin-resistant Staphylococcus aureus (MRSA) from positive blood culture
      aliquots with high specificity (signal/noise ratio of 105). 

PMID- 24899220
TI  - Trileaflet aortic valve commissural fusion: a rare cause of aortic valve disease
      and systolic ejection sounds.

PMID- 24899217
TI  - Adolescent seasonal allergic rhinitis and the impact of health-care professional
      training: cluster randomised controlled trial of a complex intervention in
      primary care.
AB  - BACKGROUND: Seasonal allergic rhinitis is typically poorly managed, particularly
      in adolescents, in whom it is responsible for considerable morbidity. Our
      previous work has demonstrated that if poorly controlled this can impair
      educational performance. AIM: The primary aim of this trial was to assess the
      impact of a primary care-based professional training intervention on clinical
      outcomes in adolescents with seasonal allergic rhinitis. METHODS: Cluster trial
      in which UK general practice staff were randomised to a short, intensive workshop
      on the evidence-based management of seasonal allergic rhinitis. The primary
      outcome measure was the change in the validated Rhinoconjunctivitis Quality of
      Life Questionnaire with Standardized Activities (RQLQ(S)) score between baseline
      and 6 weeks post intervention (minimal clinically important difference=0.5).
      Secondary outcome measures of interest included health-care professionals'
      knowledge and confidence in managing seasonal allergic rhinitis, number of
      seasonal allergic rhinitis-related consultations, relevant treatments prescribed
      and symptom scores. RESULTS: Thirty-eight general practices were randomised (20
      in the intervention arm) and 246 patients (50.2% males, mean age 15 years) were
      included in the primary outcome analysis. Health-care professionals' knowledge
      and confidence of the clinical management of seasonal allergic rhinitis improved.
      This did not, however, result in clinically or statistically significant
      improvements in RQLQ(S): -0.15, (95% confidence interval, -0.5 to +0.2). There
      were no differences in consultation frequency, treatments issued for seasonal
      allergic rhinitis or symptom scores. CONCLUSIONS: Although associated with
      increases in professionals' self-assessed confidence and understanding of
      seasonal allergic rhinitis management, this intensive training workshop did not
      translate into improvements in adolescents' disease-specific quality of life or a
      reduction in rhinitis symptoms.

PMID- 24899219
TI  - Computational modeling of Fontan physiology: at the crossroads of pediatric
      cardiology and biomedical engineering.
AB  - The Fontan operation has evolved over the last four and a half decades and is now
      widely applied to patients with various forms of "single ventricle" congenital
      heart disease. Survival has greatly improved since the early years, but long-term
      morbidity and mortality continue to occur. Modeling of Fontan geometries, both in
      vitro and using computational fluid dynamics, has been instrumental in designing
      novel changes to Fontan's operation, including the application of staged surgical
      procedures leading to a total cavopulmonary anastomosis, lateral tunnel,
      extracardiac conduit, and most recently bifurcated Y-graft modifications. In this
      review, the history of modeling of Fontan physiologies, current state-of-the-art
      methodologies, and future directions are explored. The application of these
      techniques to cardiac magnetic resonance imaging to construct patient specific
      anatomies offers the possibility of individualized surgical planning to optimize
      hemodynamics, including minimizing power loss, balancing hepatic factor
      distribution, and ultimately improving patient outcomes. 

PMID- 24899222
TI  - Human exposure to airborne aniline and formation of methemoglobin: a contribution
      to occupational exposure limits.
AB  - Aniline is an important starting material in the manufacture of polyurethane
      based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well
      described in exposed workers although information on the dose-response
      association is limited. We used an experimental design to study the association
      between aniline in air with the formation of Met-Hb in blood and the elimination
      of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers
      resulted in a time-dependent increase in Met-Hb in blood and aniline in urine.
      The maximum Met-Hb level in blood (mean 1.21 +/- 0.29 %, range 0.80-2.07 %) and
      aniline excretion in urine (mean 168.0 +/- 51.8 ug/L, range 79.5-418.3 ug/L) were
      observed at the end of exposure, with both parameters rapidly decreasing after
      the end of exposure. After 24 h, the mean level of Met-Hb (0.65 +/- 0.18 %)
      returned to the basal level observed prior to the exposure (0.72 +/- 0.19 %);
      whereas, slightly elevated levels of aniline were still present in urine (means
      17.0 +/- 17.1 vs. 5.7 +/- 3.8 ug/L). No differences between males and females as
      well as between slow and fast acetylators were found. The results obtained after
      6-h exposure were also comparable to those observed in four non-smoking
      volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were
      1.57 % and 305.6 ug/L, respectively. Overall, our results contribute to the risk
      assessment of aniline and as a result, the protection of workers from aniline
      derived adverse health effects at the workplace.

PMID- 24899221
TI  - Evaluation of global circumferential strain as prognostic marker after
      administration of beta-blockers for dilated cardiomyopathy.
AB  - The use of beta-blockers has improved the prognosis of dilated cardiomyopathy
      (DCM) and the appearance of left ventricular (LV) reverse remodeling is generally
      thought to result in a more favorable prognosis. While there are many prognostic
      predictors, not all of them are applicable to individual patients. Global
      circumferential strain (GCS) was identified as a powerful prognostic marker,
      which appears to be a better parameter than LV global function for patients with
      depressed left ventricular (LV) ejection fraction. Seventy consecutive patients
      with newly-diagnosed DCM with LVEF of 28 +/- 8 % (all <45 %) were retrospectively
      recruited. Either carvedilol or bisoprolol was titrated to a dose that was
      tolerable for each of the patients. GCS was determined as the peak global speckle
      tracking circumferential strain from the mid-LV short-axis view. LV reverse
      remodeling was defined as an absolute increase in LVEF of at least 10 % during
      8.1 +/- 5.2-month follow-up after initiation of the maintenance dose of beta
      blockers. GCS >= 5.4 % was identified as the best predictor of LV reverse
      remodeling with 91 % sensitivity and 82 % specificity, and an area under the
      curve of 0.896 (p < 0.0001). An important finding of multivariate logistic
      regression analysis was that GCS was the best independent predictor of LV reverse
      remodeling (OR 7.692; 95 % CI 2.292-25.82; p = 0.001). It should be noted that
      only 1.3 +/- 0.4 min per patient was needed to analyze GCS. In conclusions, GCS
      could result in further improvements in predicting LV reverse remodeling after
      beta-blocker administration, and have clinical implications for better management
      in daily clinical practice.

PMID- 24899224
TI  - Ataxia of cortical origin via crossed cerebellar diaschisis.

PMID- 24899225
TI  - Phase II drugs that target cholinergic receptors for the treatment of overactive
      bladder.
AB  - INTRODUCTION: Overactive bladder (OAB) is a term used to describe the symptom
      syndrome of urgency, with or without urgency incontinence, usually associated
      with frequency and nocturia. Antimuscarinics are the most widely prescribed class
      of drugs for OAB, although their systemic adverse effects limit their use in
      clinical practice as compliance. This has led to developments in the field. AREAS
      COVERED: In this review, the authors describe Phase II drugs that target
      cholinergic receptors. First, the authors present the new antimuscarinics
      (tarafenacin and afacifenacin). This is followed by reports on a combination drug
      (tolenix) containing a muscarinic antagonist (tolterodine) associated with a
      muscarinic agonist (pilocarpine). Further, the authors discuss the trials of well
      known drugs in either new combination therapy (solifenacin and mirabegron) or
      with new routes of delivery (oxybutynin vaginal ring). Finally, the authors
      examine the option of targeting nicotinic acetylcholine receptors
      (dexmecamylamine). EXPERT OPINION: Different strategies have been adopted to
      improve the efficacy and tolerability of therapeutics for OAB. Nicotinic
      receptors represent a novel therapeutic target; however, it is unlikely that
      antimuscarinic agents will be replaced as standard first-line therapy in the near
      future.

PMID- 24899223
TI  - Mutation analysis of genes in the EGFR pathway in Head and Neck cancer patients:
      implications for anti-EGFR treatment response.
AB  - BACKGROUND: Targeted therapy against the Epidermal Growth Factor Receptor (EGFR)
      is among the most promising molecular therapeutics for Head and Neck Squamous
      Cell Carcinoma (HNSCC). However, drug resistance limits the clinical efficacy of
      anti-EGFR monoclonal antibodies and no predictive biomarker has entered the
      clinic yet. METHODS: A retrospective clinical study was performed utilizing
      pathological specimens from 52 newly diagnosed HNSCC patients. These patients
      were screened for mutations in EGFR and KRAS. Tyrosine kinase mutations in EGFR
      and KRAS mutations were evaluated by high resolution melting analysis (HRMA),
      whereas EGFRvIII was determined using one-step real-time PCR. Finally, patient
      samples were screened for HPV-DNA by GP5+/6+ PCR. Survival analysis was performed
      using Kaplan-Meier analysis and significance was calculated using log-rank
      statistic. RESULTS: In our study population no EGFRvIII mutations were present.
      However, two silent mutations were found; T785T in exon 20 and R836R in exon 21
      of the EGFR gene. Additionally, HRMA revealed an abnormal KRAS melting pattern in
      7.0% of the samples. However, the KRAS StripAssay could confirm only one sample
      with a G12S mutation and none of these samples could be confirmed by direct
      sequencing. HPV DNA was present in 3/25 larynx and 9/27 oropharynx tumors.
      CONCLUSION: The low rate of EGFR and KRAS mutations in this Belgian HNSCC
      population suggests that these genes will probably not play a major role in
      predicting response to anti-EGFR therapy in HNSCC. Hence, other predictive
      markers need to be discovered in order to optimize EGFR targeting therapy.

PMID- 24899226
TI  - Immunogenetic investigation in vernal keratoconjunctivitis.

PMID- 24899227
TI  - Enhanced factor VIIIa stability of A2 domain interface variants results from an
      increased apparent affinity for the A2 subunit. Results from an increased
      apparent affinity for the A2 subunit.
AB  - Factor (F)VIIIa, a heterotrimer comprised of A1, A2, and A3C1C2 subunits, is
      labile due to the tendency of the A2 subunit to dissociate from the A1/A3C1C2
      dimer. As dissociation of the A2 subunit inactivates FVIIIa activity, retention
      of A2 defines FVIIIa stability and thus, FXase activity. Earlier results showed
      that replacing residues D519, E665, and E1984 at the A2 domain interface with Ala
      or Val reduced rates of FVIIIa decay, increasing FXa and thrombin generation. We
      now show the enhanced FVIIIa stability of these variants results from increases
      in inter-A2 subunit affinity. Using a FVIIIa reconstitution assay to monitor
      inter-subunit affinity by activity regeneration, the apparent Kd value for the
      interaction of wild-type (WT) A2 subunit with WT A1/A3C1C2 dimer (43 +/- 2 nM)
      was significantly higher than values observed for the A2 point mutants D519A/V,
      E665A/V, and E1984A/V which ranged from ~5 to ~19 nM. Val was determined to be
      the optimal hydrophobic residue at position 665 (apparent Kd = 5.1 +/- 0.7 nM) as
      substitutions with Ile or Leu at this position increased the apparent Kd value by
      ~3- and ~7-fold, respectively. Furthermore, the double mutant (D519V/E665V)
      showed an ~47-fold lower apparent Kd value (0.9 +/- 0.6 nM) than WT. Thus these
      hydrophobic mutations at the A2 subunit interfaces result in high binding
      affinities for the A2 subunit and correlate well with previously observed
      reductions in rates in FVIIIa decay. 

PMID- 24899228
TI  - Prognostic factors in Epstein-Barr virus-associated stage I-III gastric
      carcinoma: implications for a unique type of carcinogenesis.
AB  - Epstein-Barr virus-associated gastric carcinoma (EBVaGC) has distinct
      clinicopathological features. However, the prognostic factors remain unclear,
      particularly in UICC/AJCC stage I-III cancer. We retrospectively enrolled 1,020
      patients with stage I-III gastric cancer that received radical gastrectomy with
      lymphadenectomy. Formalin-fixed, paraffin-embedded surgical specimens were
      retrieved to construct tissue microarrays. EBV positivity was identified by in
      situ hybridization with EBV-encoded small RNA, and the histological
      classification was reviewed. Fifty-two cases of EBVaGC were identified,
      exhibiting a male predominance (p=0.003), a higher prevalence in stump cancer
      (p<0.001), and poorly differentiated carcinoma (p=0.010) compared with the
      controls. The survival analysis revealed no difference in survival between the
      EBVaGC cases and the EBV-negative cases (p=0.977). The multivariate analysis
      showed that EBVaGC cases with a tumor size >5 cm, non-lymphoepithelioma-like
      carcinoma (LELC), or a lymph node ratio >0.15 had a worse overall survival
      (hazard ratio 2.884, 12.178 and 19.352; p=0.027, 0.005 and <0.0001,
      respectively). The depth of tumor invasion and the number of lymph node
      metastases did not reach statistical significance (p=0.834 and 0.833,
      respectively). These prognostic factors, tumor size, LELC classification and
      lymph node ratio, may reflect a unique type of carcinogenesis of EBVaGC and may
      be considered when selecting high-risk patients for adjuvant treatment.

PMID- 24899230
TI  - A composite multivariate polygenic and neuroimaging score for prediction of
      conversion to Alzheimer's disease.
AB  - Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) are characterized by
      widespread pathological changes in the brain. At the same time, Alzheimer's
      disease is heritable with complex genetic underpinnings that may influence the
      timing of the related pathological changes in the brain and can affect the
      progression from MCI to AD. In this paper, we present a multivariate imaging
      genetics approach for prediction of conversion to Alzheimer's disease in patients
      with mild cognitive impairment. We employ multivariate pattern recognition
      approaches to obtain neuroimaging and polygenic discriminators between the
      healthy individuals and AD patients. We then design, in a linear manner, a
      composite imaging-genetic score for prediction of conversion to Alzheimer's
      disease in patients with mild cognitive impairment. We apply our approach within
      the Alzheimer's Disease Neuroimaging Initiative and show that the integration of
      polygenic and neuroimaging information improves prediction of conversion to AD.

PMID- 24899229
TI  - An update on surgical and non-surgical treatments for vaginal hypoplasia.
AB  - BACKGROUND: In women with vaginal hypoplasia, such as in Mayer-Rokitansky-Kuster
      Hauser syndrome (MRKH) and in Complete Androgen Insensitivity Syndrome (CAIS),
      surgical vaginoplasty and non-surgical self-dilation treatments are available to
      lengthen the vagina and facilitate sexual intercourse, but the best treatment
      remains controversial. Vaginal dilation has been recommended as a first-line
      treatment, because of its less invasive character and high success rate. However,
      the exploration of factors associated with compliance and long-term outcome is
      incomplete, including whether psychological counselling needs to be embedded in
      treatment to maximize efficacy. It is not known if failed vaginal dilation
      therapy jeopardizes further surgical success outcomes, especially because in a
      number of these procedures ongoing vaginal dilation is required. In addition, if
      surgery is needed, there is a lack of evidence to inform physicians regarding the
      optimum surgical technique to use. Also, it is unclear whether maintenance
      dilation therapy in case of sexual inactivity is crucial to ensure functional
      success. METHODS: In view of this ongoing debate, we performed a search of all
      published literature (English language only) restricted to the management of
      vaginal hypoplasia in patients with MRKH or CAIS from 1898 to March 2013 using
      Pubmed, Cochrane Library and Web of Science. Of the 6700 articles initially
      identified, a total of 190 studies are analysed. More specifically, by
      establishing the risk/efficacy profile (vaginal capacity, complications and long
      term durability in terms of sexual function) of the different surgical and non
      surgical reconstruction techniques, we evaluate if vaginal dilation proposed as
      the first-line technique is justified based on the evidence. RESULTS: When
      anatomical success was defined as a length of >=7 cm and functional success as
      coitus, all vaginoplasty techniques yielded significantly higher success rates
      (>90 versus 75% after vaginal dilation), irrespective of underlying diagnosis or
      start vaginal length. When functional success was defined as 'satisfaction with
      sex', including non-genital sex, differences disappeared. Failed dilation therapy
      does not preclude anatomical (nor functional) success if vaginoplasty afterwards
      is necessary. Traction vaginoplasty seems to have the highest anatomical (99%)
      and functional success rates (96%), whereas both split- and full-thickness skin
      graft procedures and intestinal procedures have the lowest successful outcomes
      (83-95%). Overall, complication rates were significantly lower within the vaginal
      dilation groups when compared with the different vaginoplasty techniques.
      Although no randomized control data exist regarding maintenance dilation, the
      available evidence suggests that continued dilation is needed to maintain patency
      in periods of coital inactivity. Despite the expectancy that the probability of
      further positive outcomes is maximized with psychological counselling, this could
      not be confirmed. CONCLUSIONS: As the medical literature lacks high-quality
      comparative outcome studies and prospective, longitudinal studies are scarce, no
      evidence-based treatment guidelines can be provided. However, because of the
      physically low complication rate and an overall success chance of 75%, vaginal
      dilation as first choice treatment seems to be justified. Overall, the
      laparoscopic Vecchietti procedure, becoming more and more available in
      specialized centres, is considered an appropriate surgical option in patients who
      are poorly compliant and failed dilation therapy, or for those who do not want to
      start with vaginal dilation therapy. Future approaches need to raise a wider
      range of psychosexually oriented questions, elucidate the relationship between
      vaginal depth and satisfactory outcomes and gain additional experience concerning
      the format of acceptable and efficient psychological care.

PMID- 24899231
TI  - Conditional disruption of interactions between Galphai2 and regulator of G
      protein signaling (RGS) proteins protects the heart from ischemic injury.
AB  - BACKGROUND: Regulator of G protein signaling (RGS) proteins suppress G protein
      coupled receptor signaling by catalyzing the hydrolysis of Galpha-bound guanine
      nucleotide triphosphate. Transgenic mice in which RGS-mediated regulation of
      Galphai2 is lost (RGS insensitive Galphai2G184S) exhibit beneficial (protection
      against ischemic injury) and detrimental (enhanced fibrosis) cardiac phenotypes.
      This mouse model has revealed the physiological significance of RGS/Galphai2
      interactions. Previous studies of the Galphai2G184S mutation used mice that
      express this mutant protein throughout their lives. Thus, it is unclear whether
      these phenotypes result from chronic or acute Galphai2G184S expression. We
      addressed this issue by developing mice that conditionally express Galphai2G184S.
      METHODS: Mice that conditionally express RGS insensitive Galphai2G184S were
      generated using a floxed minigene strategy. Conditional expression of
      Galphai2G184S was characterized by reverse transcription polymerase chain
      reaction and by enhancement of agonist-induced inhibition of cAMP production in
      isolated cardiac fibroblasts. The impact of conditional RGS insensitive
      Galphai2G184S expression on ischemic injury was assessed by measuring contractile
      recovery and infarct sizes in isolated hearts subjected to 30 min ischemia and 2
      hours reperfusion. RESULTS: We demonstrate tamoxifen-dependent expression of
      Galphai2G184S, enhanced inhibition of cAMP production, and cardioprotection from
      ischemic injury in hearts conditionally expressing Galphai2G184S. Thus the
      cardioprotective phenotype previously reported in mice expressing Galphai2G184S
      does not require embryonic or chronic Galphai2G184S expression. Rather,
      cardioprotection occurs following acute (days rather than months) expression of
      Galphai2G184S. CONCLUSIONS: These data suggest that RGS proteins might provide
      new therapeutic targets to protect the heart from ischemic injury. We anticipate
      that this model will be valuable for understanding the time course (chronic
      versus acute) and mechanisms of other phenotypic changes that occur following
      disruption of interactions between Galphai2 and RGS proteins.

PMID- 24899232
TI  - Stiffness of left ventricular cardiac fibroblasts is associated with ventricular
      dilation in patients with recent-onset nonischemic and nonvalvular
      cardiomyopathy.
AB  - BACKGROUND: Ventricular dilation is known as a pivotal predictor in recent-onset
      cardiomyopathy (ROCM), but its pathophysiology is not fully understood. In the
      present study we investigated whether single-cell stiffness of right and left
      ventricular-derived fibroblasts has an effect on cardiac phenotype in patients
      with ROCM. METHODS AND RESULTS: Patients with endomyocardial biopsy-proven ROCM
      were included (n=10). Primary cardiac fibroblasts (CFBs) were cultured from left
      and right ventricular endomyocardial biopsies and their single-cell stiffness was
      analyzed by quantification of Young's modulus using colloidal probe atomic force
      microscopy. Cardiac fibrosis was analyzed by Masson's trichrome staining. CFBs
      from the left ventricle showed significantly decreased stiffness when compared
      with CFBs from the right ventricle, indexed by decreased stiffness (Young's
      modulus 3,374+/-389 vs. 4,837+/-690 Pa; P<0.05). Young's modulus of CFBs derived
      from the left ventricle correlated negatively with the left ventricular end
      diastolic dimension derived from 2-dimensional echocardiography (R(2)=0.77;
      P<0.01). Neither left nor right ventricular fibrosis correlated with the
      respective ventricular dimensions. CONCLUSIONS: Our data suggest that a decrease
      in single-cell stiffness of left ventricular fibroblasts could trigger left
      ventricular dilation in patients with ROCM. This implies a new potential
      mechanism for the ventricular dilation with this disease.

PMID- 24899233
TI  - Nobori biolimus-eluting stent vs. permanent polymer drug-eluting stents in
      patients undergoing percutaneous coronary intervention.
AB  - BACKGROUND: Permanent polymer coatings on drug-eluting stents (DES) surface have
      been identified as triggers of adverse events following percutaneous coronary
      intervention (PCI). However, efficacy and safety data for the Nobori biolimus
      eluting stent (BES), a biodegradable polymer DES, are limited, so the aim of this
      study was to evaluate clinical outcomes associated with the Nobori BES compared
      with permanent polymer DES in patients undergoing PCI. METHODS AND RESULTS:
      Randomized trials comparing Nobori BES vs. other DES were included in the meta
      analysis. The 12-month clinical endpoints were: target lesion revascularization
      (TLR), all-cause mortality, myocardial infarction (MI) and stent thrombosis (ST).
      Seven trials totaling 12,090 PCI patients met the inclusion criteria. Nobori BES
      vs. other DES had a comparable risk of TLR (odds ratio [OR] 0.94; 95% confidence
      interval [CI], 0.66-1.34; P=0.74), mortality (OR 1.00; 95% CI, 0.78-1.28;
      P=0.98), MI (OR 1.10; 95% CI, 0.87-1.40; P=0.42) and definite/probable ST (OR
      1.01; 95% CI, 0.45-2.25; P=0.99). Despite Nobori BES showing similar clinical
      results to sirolimus-, everolimus- and zotarolimus-eluting stents, it was
      superior to paclitaxel-eluting stents in reducing the risk of TLR (OR 0.31; 95%
      CI, 0.10-0.90; P=0.03)CONCLUSIONS:Nobori BES use is associated with a similar
      safety and efficacy as permanent polymer DES at 1-year follow-up, albeit it is
      superior to paclitaxel-eluting stents in terms of TLR. Long-term follow-up data
      are needed in order to establish whether polymer degradation related to Nobori
      BES implantation improves clinical outcomes.

PMID- 24899234
TI  - Residual problems with repaired tetralogy of fallot.

PMID- 24899235
TI  - Inferring cellular regulatory networks with Bayesian model averaging for linear
      regression (BMALR).
AB  - Bayesian network and linear regression methods have been widely applied to
      reconstruct cellular regulatory networks. In this work, we propose a Bayesian
      model averaging for linear regression (BMALR) method to infer molecular
      interactions in biological systems. This method uses a new closed form solution
      to compute the posterior probabilities of the edges from regulators to the target
      gene within a hybrid framework of Bayesian model averaging and linear regression
      methods. We have assessed the performance of BMALR by benchmarking on both in
      silico DREAM datasets and real experimental datasets. The results show that BMALR
      achieves both high prediction accuracy and high computational efficiency across
      different benchmarks. A pre-processing of the datasets with the log
      transformation can further improve the performance of BMALR, leading to a new top
      overall performance. In addition, BMALR can achieve robust high performance in
      community predictions when it is combined with other competing methods. The
      proposed method BMALR is competitive compared to the existing network inference
      methods. Therefore, BMALR will be useful to infer regulatory interactions in
      biological networks. A free open source software tool for the BMALR algorithm is
      available at https://sites.google.com/site/bmalr4netinfer/.

PMID- 24899236
TI  - Inward-rectifying potassium channelopathies: new insights into disorders of
      sodium and potassium homeostasis.
AB  - Inward-rectifying potassium (Kir) channels allow more inward than outward
      potassium flux when channels are open in mammalian cells. At physiological
      resting membrane potentials, however, they predominantly mediate outward
      potassium flux and play important roles in regulating the resting membrane
      potential in diverse cell types and potassium secretion in the kidneys. Mutations
      of Kir channels cause human hereditary diseases collectively called Kir
      channelopathies, many of which are characterized by disorders of sodium and
      potassium homeostasis. Studies on these genetic Kir channelopathies have shed
      light on novel pathophysiological mechanisms, including renal sodium and
      potassium handling, potassium shifting in skeletal muscles, and aldosterone
      production in the adrenal glands. Here, we review several recent advances in Kir
      channels and their clinical implications in sodium and potassium homeostasis. 

PMID- 24899237
TI  - Prevalence of herpesviruses at onset of idiopathic nephrotic syndrome.
AB  - BACKGROUND: Idiopathic nephrotic syndrome (INS) is likely a primary immune
      disorder, but viruses might also be involved in the mechanisms of the disease.
      Here, we investigate the link between herpesvirus infection and the first
      manifestation of INS in children. METHODS: A prospective, multicentre, and
      population-based case-control study called NEPHROVIR included 164 patients, aged
      6 months to 15 years old, newly diagnosed with INS, and 233 controls matched for
      gender, age, and period of sample. The analysis was done on 124 patients and 196
      controls. Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6
      (HHV-6), and human herpesvirus-7 (HHV-7) DNA prevalence at diagnosis were
      assessed from whole peripheral blood samples, as well as EBV and CMV viral load
      and seroprevalence. RESULTS: EBV DNA was significantly more prevalent in cases
      than in controls (50.8 vs 29.1 %; OR = 2.6; p = 0.0002), with no difference in
      viral load. A significant difference was also found for CMV (11.3 vs 3.6 %; p =
      0.02) and HHV-7 (83 vs 72 %; p = 0.02) DNA prevalence between cases and controls.
      There were significantly more EBV and CMV recent infections or reactivations
      based on VCA-IgM and CMV IgM in cases than controls, while there were no
      differences in IgG seroprevalence. CONCLUSION: The prevalence of positive EBV DNA
      detection and recent infection or reactivation is higher in children at onset of
      INS compared to a population matched for age, gender, and time of sampling.

PMID- 24899238
TI  - A voxel-based morphometry study of regional gray and white matter correlate of
      self-disclosure.
AB  - Self-disclosure is an important performance in human social communication.
      Generally, an individual is likely to have a good physical and mental health if
      he is prone to self-disclosure under stressful life events. However, as for now,
      little is known about the neural structure associated with self-disclosure.
      Therefore, in this study, we used voxel-based morphometry to explore regional
      gray matter volume (rGMV) and white matter volume (rWMV) associated with self
      disclosure measured by the Jourard Self-disclosure Questionnaire in a large
      sample of college students. Results showed that individual self-disclosure was
      significantly and positively associated with rGMV of the left postcentral gyrus,
      which might be related to strengthen individual's ability of body feeling; while
      self-disclosure was significantly and negatively associated with rGMV of the
      right orbitofrontal cortex (OFC), which might be involved in increased positive
      emotion experience seeking (intrinsically rewarding). In addition, individual
      self-disclosure was also associated with smaller rWMV in the right inferior
      parietal lobule (IPL). These findings suggested a biological basis for individual
      self-disclosure, distributed across different gray and white matter areas of the
      brain. 

PMID- 24899239
TI  - Surveillance of healthcare-associated infections in Piemonte, Italy: results from
      a second regional prevalence study.
AB  - BACKGROUND: A prevalence survey of healthcare-associated infections (HAIs) was
      previously performed in the Piemonte region in 2000. In the decade following the
      survey, many studies were performed at both the regional and hospital levels, and
      training courses were developed to address issues highlighted by the survey. In
      2010, a second regional prevalence study was performed. The aim of this paper is
      to present the results of the second prevalence study and discuss them within the
      context of the HAI prevention and control programmes that have been implemented
      in the decade since the original survey was conducted. METHODS: The study
      involved all public hospitals in the Piemonte region. Uni- and multivariate
      analyses were performed to assess the main risk factors associated with HAIs,
      including both overall and site-specific infections. RESULTS: A total of 7841
      patients were enrolled: 6.8% were affected by at least one HAI. The highest
      prevalence of HAIs was found in intensive care units (18.0%, 95% CI 14.0-22.6),
      while UTIs presented the highest relative frequency (26.7%), followed by
      respiratory tract infections (21.9%). The age of the patient, hospital size and
      urinary and central venous catheter status were significantly associated with
      HAIs. CONCLUSIONS: The study results showed an increase in HAI prevalence,
      despite prevention and control efforts, as well as training implemented after the
      first regional survey. Nevertheless, these data are consistent with the current
      literature. Furthermore, despite its limits, the prevalence approach remains an
      important means for involving healthcare workers, emphasising HAIs and revealing
      critical problems that need be addressed.

PMID- 24899240
TI  - Synthesis of cyclic alkenylsiloxanes by semihydrogenation: a stereospecific route
      to (Z)-alkenyl polyenes.
AB  - Cyclic alkenylsiloxanes were synthesized by semihydrogenation of alkynylsilanes-a
      reaction previously plagued by poor stereoselectivity. The silanes, which can be
      synthesized on multigram scale, undergo Hiyama-Denmark coupling to give (Z)
      alkenyl polyene motifs found in bioactive natural products. The ring size of the
      silane is crucial: five-membered cyclic siloxanes also couple under fluoride-free
      conditions, whilst their six-membered homologues do not, enabling orthogonality
      within this structural motif. 

PMID- 24899241
TI  - Effect of virtual reality distraction on pain among patients with hand injury
      undergoing dressing change.
AB  - AIMS AND OBJECTIVES: To assess the effect of virtual reality distraction on pain
      among patients with a hand injury undergoing a dressing change. BACKGROUND:
      Virtual reality distraction can effectively alleviate pain among patients
      undergoing a dressing change. Clinical research has not addressed pain control
      during a dressing change. DESIGN: A randomised controlled trial was performed.
      METHODS: In the first dressing change sequence, 98 patients were randomly divided
      into an experimental group and a control group, with 49 cases in each group. Pain
      levels were compared between the two groups before and after the dressing change
      using a visual analog scale. The sense of involvement in virtual environments was
      measured using the Pearson correlation coefficient analysis, which determined the
      relationship between the sense of involvement and pain level. RESULTS: The
      difference in visual analog scale scores between the two groups before the
      dressing change was not statistically significant (t = 0.196, p > 0.05), but the
      scores became statistically significant after the dressing change (t = -30.792, p
      < 0.01). The correlation between the sense of involvement in a virtual
      environment and pain level during the dressing was statistically significant
      (R(2) = 0.5538, p < 0.05). CONCLUSION: Virtual reality distraction can
      effectively alleviate pain among patients with a hand injury undergoing a
      dressing change. Better results can be obtained by increasing the sense of
      involvement in a virtual environment. RELEVANCE TO CLINICAL PRACTICE: Virtual
      reality distraction can effectively relieve pain without side effects and is not
      reliant on a doctor's prescription. This tool is convenient for nurses to use,
      especially when analgesics are unavailable.

PMID- 24899242
TI  - The effect of mindfulness training prior to total joint arthroplasty on post
      operative pain and physical function: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Osteoarthritis is a leading cause of disability in developed nations.
      In Australia it afflicts 16.5% of the adult population. Total joint arthroplasty
      is considered the treatment of choice for end stage osteoarthritis. The number of
      total joint arthroplasties undertaken in Australia has doubled over the last
      decade (more than 80,000 procedures in 2011). The incidence of pre-operative
      psychological distress in this group of patients is reported between 30% and 60%
      and pre-operative psychological distress is associated with poorer pain and
      functional outcomes after surgery. This study will use a mindfulness-based
      psychological intervention to enhance outcomes in people undergoing total joint
      arthroplasty and, in addition, will test hypotheses about coping with chronic
      illness in an aged population. This study is the first of its kind and will
      provide a greater understanding of the role of a mental health enhancement
      program on the physical recovery of total joint arthroplasty patients.
      METHODS/DESIGN: One hundred and fifty people with end-stage arthritis on the
      waiting list for total hip or knee arthroplasty will be recruited and randomly
      allocated to one of two groups using computer-generated block randomisation. A
      randomised controlled trial adhering to CONSORT guidelines will evaluate the
      efficacy of a mindfulness training program (weekly group-based classes in
      mindfulness practice, 2 1/2 hours, for 8 weeks plus a 7-hour Saturday session in
      Week 6) prior to total joint arthroplasty, compared to a "standard care" group
      who will undergo routine total joint arthroplasty. Primary outcomes will be
      evaluated by a blinded examiner at baseline, 3 and 12 months post-surgery, using
      a validated self-reported pain and physical function scale. Secondary outcomes
      will include i) a range of validated measures of psychological wellbeing and ii)
      health economic analysis. All analyses will be conducted on an intention to treat
      basis using linear regression models. Health economic modelling will be applied
      to estimate the potential cost-effectiveness of mindfulness training and total
      joint arthroplasty. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry (ANZCTRN12611001184965). Date of registration; 15th November 2011.

PMID- 24899244
TI  - Freshness maintenance of cherries ready for consumption using convenient,
      microperforated, bio-based packaging.
AB  - BACKGROUND: Current consumer demand for high-quality ready-to-eat fresh fruit in
      convenient bio-based packaging was met utilizing sanitized stem-free sweet
      cherries and a polylactic acid (PLA) cup with a PLA peelable microperforated lid.
      The newly developed packaging system was compared with the petroleum-based
      macroperforated bag currently used for retail. RESULTS: After 27 days of storage
      at 1  degrees C, the PLA package maintained the cherry firmness, compared with a
      50% reduction of the controls. No fungal decay was detected in the cherries
      stored in PLA, while the controls were non-marketable after 21 days. The PLA
      package allowed minimal weight loss (0.8%), compared with a weight loss of
      approximately 16% in the controls. Differences in the cherry aroma, color,
      acidity, soluble solids content, pH and quality index were also caused by the
      packaging type. A consumer sensory evaluation showed that cherries stored in PLA
      packages were more acceptable than those of the controls for appearance, texture,
      flavor and overall acceptability. CONCLUSION: The new package matched both the
      consumer demand for high-quality fresh fruit ready for consumption in convenient
      bio-based packaging and the extended fruit marketability and consumer
      satisfaction desired by industry.

PMID- 24899245
TI  - Impact of obstetric history on the risk of spontaneous preterm birth in singleton
      and multiple pregnancies: a systematic review.
AB  - BACKGROUND: Information about the recurrence of spontaneous preterm birth in
      subsequent twin/singleton pregnancies is scattered. OBJECTIVES: To quantify the
      risk of recurrence of spontaneous preterm birth in different subtypes of
      subsequent pregnancies. SEARCH STRATEGY: An electronic literature search in OVID
      MEDLINE and EMBASE, complemented by PubMed, to find recent studies. SELECTION
      CRITERIA: Studies comparing the risk of spontaneous preterm birth after a
      previous preterm and previous term pregnancy. DATA COLLECTION AND ANALYSIS: The
      absolute risk of recurrence with a 95% confidence interval and the absolute risk
      of preterm birth after a term delivery were calculated. Data from studies were
      pooled using the Mantel-Haenszel method. MAIN RESULTS: We detected 13 relevant
      studies. The risk of recurrence of preterm birth was significantly increased in
      all preterm pregnancy subtypes, compared with their term counterparts. Women
      pregnant with twins after a previous preterm singleton had the highest absolute
      risk of recurrence (57.0%, 95% CI 51.9-61.9%), and after a previous term
      singleton their absolute risk was 25% (95% CI 24.3-26.5%). Women pregnant with a
      singleton after a previous preterm twin pregnancy have an absolute recurrence
      risk of 10% (95% CI 8.2-12.3%), whereas a singleton pregnancy after delivering a
      previous twin up to term yields a low absolute risk of only 1.3% (95% CI 0.8
      2.2). Women pregnant with a singleton after a previous preterm singleton have an
      absolute recurrence risk of 20% (95% CI 19.9-20.6). AUTHOR'S CONCLUSIONS: The
      risk of recurrence of preterm birth is influenced by the singleton/twin order in
      both pregnancies, and varies between 10% for a singleton after previous preterm
      twins to 57% for twins after a previous preterm singleton.

PMID- 24899243
TI  - Locally optimal extracellular stimulation for chaotic desynchronization of neural
      populations.
AB  - We use optimal control theory to design a methodology to find locally optimal
      stimuli for desynchronization of a model of neurons with extracellular
      stimulation. This methodology yields stimuli which lead to positive Lyapunov
      exponents, and hence desynchronizes a neural population. We analyze this
      methodology in the presence of interneuron coupling to make predictions about the
      strength of stimulation required to overcome synchronizing effects of coupling.
      This methodology suggests a powerful alternative to pulsatile stimuli for deep
      brain stimulation as it uses less energy than pulsatile stimuli, and could
      eliminate the time consuming tuning process. 

PMID- 24899246
TI  - A case of seborrheic keratosis with clear cell change.

PMID- 24899247
TI  - Patient with a history of indurated plaques and renal disease.

PMID- 24899248
TI  - Potential prognostic and diagnostic application of a novel monoclonal antibody
      against keratinocyte growth factor receptor.
AB  - KGFR is involved in the pathogenesis of several human cancers. In this study, we
      generated and characterized a monoclonal antibody specific to KGFR (SC-101 mAb)
      and evaluated its potential use in basic research and as a diagnostic and
      prognostic tool. The specificity and biological activity of the SC-101 mAb were
      evaluated by Western blotting, immunofluorescence, and immunoprecipitation
      analyses on various cell lines. KGFR expression in breast, pancreatic, and
      thyroid carcinoma was assessed by immunohistochemistry (IHC) with SC-101 mAb.
      KGFR expression levels revealed by SC-101 mAb resulted to increase proportionally
      with tumor grade in breast and pancreatic cancer. In addition, SC-101 mAb was
      able to detect KGFR down-modulation in thyroid cancer. SC-101 mAb might represent
      a useful tool for basic research applications, and it could also contribute to
      improve the accuracy of diagnosis and prognosis of epithelial tumors. 

PMID- 24899249
TI  - Association of purine asymmetry, strand-biased gene distribution and PolC within
      Firmicutes and beyond: a new appraisal.
AB  - BACKGROUND: The Firmicutes often possess three conspicuous genome features:
      marked Purine Asymmetry (PAS) across two strands of replication, Strand-biased
      Gene Distribution (SGD) and presence of two isoforms of DNA polymerase III alpha
      subunit, PolC and DnaE. Despite considerable research efforts, it is not clear
      whether the co-existence of PAS, PolC and/or SGD is an essential and exclusive
      characteristic of the Firmicutes. The nature of correlations, if any, between
      these three features within and beyond the lineages of Firmicutes has also
      remained elusive. The present study has been designed to address these issues.
      RESULTS: A large-scale analysis of diverse bacterial genomes indicates that PAS,
      PolC and SGD are neither essential nor exclusive features of the Firmicutes. PolC
      prevails in four bacterial phyla: Firmicutes, Fusobacteria, Tenericutes and
      Thermotogae, while PAS occurs only in subsets of Firmicutes, Fusobacteria and
      Tenericutes. There are five major compositional trends in Firmicutes: (I) an
      explicit PAS or G + A-dominance along the entire leading strand (II) only G
      dominance in the leading strand, (III) alternate stretches of purine-rich and
      pyrimidine-rich sequences, (IV) G + T dominance along the leading strand, and (V)
      no identifiable patterns in base usage. Presence of strong SGD has been observed
      not only in genomes having PAS, but also in genomes with G-dominance along their
      leading strands - an observation that defies the notion of co-occurrence of PAS
      and SGD in Firmicutes. The PolC-containing non-Firmicutes organisms often have
      alternate stretches of R-dominant and Y-dominant sequences along their genomes
      and most of them show relatively weak, but significant SGD. Firmicutes having G +
      A-dominance or G-dominance along LeS usually show distinct base usage patterns in
      three codon sites of genes. Probable molecular mechanisms that might have
      incurred such usage patterns have been proposed. CONCLUSION: Co-occurrence of
      PAS, strong SGD and PolC should not be regarded as a genome signature of the
      Firmicutes. Presence of PAS in a species may warrant PolC and strong SGD, but
      PolC and/or SGD not necessarily implies PAS.

PMID- 24899250
TI  - Emerging targeted therapies for melanoma treatment (review).
AB  - Cutaneous melanoma is an aggressive cancer with a poor prognosis for patients
      with advanced disease. The identification of several key molecular pathways
      implicated in the pathogenesis of melanoma has led to the development of novel
      therapies for this devastating disease. In melanoma, both the Ras/Raf/MEK/ERK
      (MAPK) and the PI3K/AKT (AKT) signalling pathways are constitutively activated
      through multiple mechanisms. Targeting various effectors of these pathways with
      pharmacologic inhibitors may inhibit melanoma cell growth and angiogenesis.
      Ongoing clinical trials provide hope to improve progression-free survival of
      patients with advanced melanoma. This review summarizes the most relevant studies
      focused on the specific action of these new molecular targeted agents. Mechanisms
      of resistance to therapy are also discussed. 

PMID- 24899251
TI  - Nonsilver treatment vs. silver sulfadiazine in treatment of partial-thickness
      burn wounds in children: a systematic review and meta-analysis.
AB  - The evidence for application of silver-containing dressings and topicals in the
      treatment of partial-thickness burns in pediatric patients is largely based on
      clinical trials involving adult patients despite the important differences
      between the skin of children and adults. A systematic review and meta-analysis
      was performed of all randomized controlled trials comparing nonsilver treatment
      with silver-containing dressings and silver topical agents in children with
      partial-thickness burns in the acute stage. Endpoints were wound healing,
      grafting, infection, pain, number of dressing changes, length of hospital stay,
      and scarring. Seven randomized controlled trials were included involving 473
      participants. All trials used silver sulfadiazine as control in comparison with
      five different nonsilver treatments. Most trials were of moderate quality with
      high risk of bias. Use of nonsilver treatment led to shorter wound healing time
      (weighted mean difference: -3.43 days, 95% confidence interval: -4.78, -2.07),
      less dressing changes (weighted mean difference: -19.89 dressing changes, 95%
      confidence interval: -38.12, -1.66), and shorter length of hospital stay
      (weighted mean difference: -2.07 days, 95% confidence interval: -2.63, -1.50)
      compared with silver sulfadiazine treatment, but no difference in the incidence
      of wound infection or grafting was found. In conclusion, nonsilver treatment may
      be preferred over silver sulfadiazine, but high-quality randomized controlled
      trials are needed to validly confirm the effectiveness of silver containing
      preparations, in particular silver-containing dressings, above nonsilver
      treatments. 

PMID- 24899252
TI  - Restoration of joint congruency and the glenoidal labrum after arthroscopic
      revision Bankart repair: a MRI match-paired analysis comparing primary Bankart
      repair and the uninjured labrum.
AB  - PURPOSE: The restoration of joint congruency and labrum slope and height after
      arthroscopic revision Bankart repair (RB) compared to the primary arthroscopic
      Bankart repair (PB) remain unclear. METHODS: Twenty-three consecutive patients
      after RB with minor glenoid deficits were matched to 23 patients after PB and
      retrospectively followed by a score system and native 1.5 T magnetic resonance
      imaging (MRI) assessment. Bankart repair surgeries were performed using double
      loaded knotless suture anchors. The glenoidal (GAA) and labral articulation arc
      (LAA), labrum slope, height index and morphology were assessed separately for the
      anterior and inferior glenoid and compared to 23 healthy volunteers [radiologic
      control group (RC)]. RESULTS: Arthroscopic revision Bankart repair showed 28.0
      months post-operative equivalent anterior labral congruency (LAA, 9.3 degrees /PB
      9.9 degrees /RC 10.1 degrees ) and inferior (LAA 9.9 degrees /PB 9.6 degrees /RC
      10.5 degrees ). The anterior GAA remain decreased (54.6 degrees /PB 55.7 degrees
      /RC 58.0 degrees ) with an original inferior GAA (85.1 degrees /PB 83.2 degrees
      /RC 83.8 degrees ). The RB labrum was slightly decreased anteriorly (slope 22.9
      degrees /PB 23.9 degrees /RC 24.6 degrees ; height index 2.4/PB 3.0/RC 3.2). The
      inferior portion had an equivalent labrum slope (23.8 degrees /PB 24.7 degrees
      /RC 25.1 degrees ), but a decreased height index (2.1/PB 2.2/RC 2.3). Morphologic
      labrum analysis revealed significant changes between all three groups. The
      clinical outcome after revision surgery was good-to-excellent, but inferior to
      the primary stabilization and without influence of joint congruency and labrum
      morphology to the clinical outcome. CONCLUSION: A properly applied arthroscopic
      revision of a Bankart repair generates sufficient restoration of the
      anteroinferior labral joint congruency and good clinical results. STUDY DESIGN:
      Case series.

PMID- 24899253
TI  - Degradation of poly-D-L-lactide (PDLLA) interference screws (Megafix (r)).
AB  - INTRODUCTION: Interference screw fixation is a standard procedure in anterior
      cruciate ligament (ACL) replacement. Aim of this study was to evaluate the
      degradation process of Poly-D-L-lactide (PDLLA) interference screws used for
      tibial ACL graft fixation. MATERIALS AND METHODS: We evaluated magnetic resonance
      imaging (MRI) scans of 18 patients who underwent ACL revision surgery at
      different time points after anatomic ACL reconstruction. At primary surgery, a
      tibial hybrid fixation was performed with a degradable interference (IF) screw
      made of PDLLA (Megafix((r))) and a button. RESULTS: MRI revealed three different
      phases of degradation of the PDLLA screw. 6-8 months after surgery the IF screw
      was clearly visible as a well-defined structure on MRI and CT scan. After 12-16
      months, the screws appeared less defined with central ingrowths' of connective
      tissue. In some cases only fragmented screw material was visible. At these time
      points, there was a slight edema surrounding the tunnel visible on MRI. After 22
      months and later, the mean screw site densities were comparable with the
      surrounding bone density. There was no edema or signs of inflammation around the
      bone tunnels visible. Presence of cystic or osteolytic changes was not detected.
      CONCLUSION: After 22 months, a PDLLA screw may not interfere with ACL revision
      surgery. Regarding the degradation process of PDLLA screws, we noted three
      different phases. Furthermore, the degradation process observed by MRI resembles
      to that described by animal studies. The PDLLA screws fully absorb and are
      partially replaced by bone. The degradation process in humans seems to be longer
      than that described in animals.

PMID- 24899254
TI  - The shortcoming and deficiency in "Risk factors for complications and in-hospital
      mortality following hip fractures: a study using the National Trauma Data Bank".

PMID- 24899255
TI  - Copper, nickel and zinc speciation in a biosolid-amended soil: pH adsorption
      edge, MU-XRF and MU-XANES investigations.
AB  - Metal solid phase speciation plays an important role in the control of the long
      term stability of metals in biosolid-amended soils. The present work used pH
      adsorption edge experiments and synchrotron-based spectroscopy techniques to
      understand the solid phase speciation of copper, nickel and zinc in a biosolid
      amended soil. Comparison of metal adsorption edges on the biosolid-amended soil
      and the soil sample showed that Cu, Ni, and Zn can be retained by both soil and
      biosolid components such as amorphous iron phases, organic matter and clay
      minerals. These data are combined with microscopic results to obtain structural
      information about the surface complexes formed. Linear combination fitting of K
      edge XANES spectra of metal hot-spots indicated consistent differences in metal
      speciation between metals. While organic matter plays a dominant role in Ni
      binding in the biosolid-amended soil, it was of lesser importance for Cu and Zn.
      This study suggests that even if the metals can be associated with soil
      components (clay minerals and organic matter), biosolid application will increase
      metals retention in the biosolid-amended soil by providing reactive organic
      matter and iron oxide fractions. Among the studied metals, the long-term mobility
      of Ni could be affected by organic matter degradation while Cu and Zn are
      strongly associated with iron oxides. 

PMID- 24899256
TI  - Enantioselective bioaccumulation and toxic effects of fipronil in the earthworm
      Eisenia foetida following soil exposure.
AB  - BACKGROUND: Enantiomers of chiral pesticides often have different bioactivity,
      toxicity and environmental behaviours. Fipronil has been used in racemate for
      agricultural purposes against soil insects, leading to increased inputs into soil
      environments and complex biota exposures. To understand the potential risk
      associated with fipronil enantiomer exposure, subchronic toxicity and
      bioaccumulation tests with earthworms (Eisenia foetida) in fipronil-spiked soils
      were evaluated under laboratory conditions. RESULTS: Enantioselective toxicity
      was measured in E. foetida biomass after 28 days of subchronic exposure, with
      increased toxicity from racemate and S-fipronil compared with R-fipronil. The
      bioaccumulation of fipronil in earthworm tissues was also enantioselective, with
      a preferential accumulation of S-fipronil, and the enantiomer fraction was
      approximately 0.56-0.60. During soil exposure, fipronil was transformed primarily
      into fipronil sulfide, sulfone and amide, and E. foetida rapidly accumulated
      fipronil and sulfone. CONCLUSION: This work demonstrates the enantioselective
      subchronic toxicity and bioaccumulation of enantiomers of fipronil in E. foetida.
      The earthworm tissues exhibited a relative enrichment of fipronil and fipronil
      sulfone, and these compounds might biomagnify (with a biota-to-soil accumulation
      factor of >=1.0 kgOCkglip-1), allowing for the possible trophic transfer and/or
      bioaccumulation of all these chemicals if earthworms were consumed by predator
      organisms.

PMID- 24899257
TI  - Novel pyridyl- or isoquinolinyl-substituted indolines and indoles as potent and
      selective aldosterone synthase inhibitors.
AB  - Pathologically, high levels of aldosterone are associated with severe
      cardiovascular diseases such as congestive heart failure, hypertension, and
      myocardial fibrosis. The inhibition of aldosterone synthase (CYP11B2) to reduce
      aldosterone levels has been proposed as a promising treatment for diseases
      related to CYP11B2 because it is the crucial enzyme in the biosynthesis of
      aldosterone. A series of novel pyridyl- or isoquinolinyl-substituted indolines
      and indoles was designed via a ligand-based approach. The synthesized compounds
      were tested and found to be strong CYP11B2 inhibitors. The most potent ones
      showed IC50 values of less than 3 nM, being similarly potent as fadrozole and
      LCI699. Among them, compounds 14 and 23 showed good selectivity over the highly
      homologous CYP11B1, with selectivity factors (SF = IC50 CYP11B1/IC50 CYP11B2)
      around 170; thus, they are superior to fadrozole and LCI699 (SFs < 15). These
      potent CYP11B2 inhibitors exhibited no inhibition (IC50 > 50 MUM) of a panel of
      hepatic CYP enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 and the
      crucial steroidogenic enzymes, CYP17 and CYP19. Because of these advantageous
      profiles, compounds 14 and 23 are considered to be candidates for further in vivo
      evaluation.

PMID- 24899258
TI  - Global Policy Review of Recommendations on Cotrimoxazole Prophylaxis among People
      Living with HIV.
AB  - The Joint United Nations Programme on HIV/AIDS (UNAIDS) Treatment 2015 calls for
      expanded access to HIV care and treatment, including cotrimoxazole preventive
      therapy (CPT), for prevention of HIV-related morbidity and mortality. We review
      115 national guidelines from 92 countries for recommendations on CPT for adults
      and adolescents and determine the level of consistency with the World Health
      Organization (WHO) guidelines. Of the 66 countries with recommendations, 5 (8%)
      countries recommend lifelong CPT for people living with HIV; 19 (29%) countries
      recommend a CD4 count threshold of <=350 cells/mm(3) or WHO clinical stages III
      and IV or II, III, and IV; and 19 (29%) countries recommend a CD4 count threshold
      of <=200 cells/mm(3). Of the 48 countries with recommendations on discontinuing
      CPT, 25 (52%) countries recommend discontinuation of cotrimoxazole when the CD4
      count is >200 cells/mm(3). World Health Organization guidelines offer countries
      flexibility on the use of CPT, and countries are recommending a wide range of CD4
      counts and WHO clinical stage criteria for prophylaxis initiation and
      discontinuation.

PMID- 24899259
TI  - Medical risks and benefits of newborn male circumcision in the United States:
      physician perspectives.
AB  - INTRODUCTION: In 2012, the American Academy of Pediatrics (AAP) and the American
      Congress of Obstetricians and Gynecologists (ACOG) published recommendations that
      physicians should discuss with parents the benefits and risks of newborn male
      circumcision. Our objective was to assess physicians' perspectives of newborn
      male circumcision. METHODS: A self-administered, cross-sectional electronic
      survey of US physicians was conducted in 2008 (N = 1500). RESULTS: Approximately
      one-third (33.2%) of the respondents reported that their current perspective was
      that the medical benefits outweigh the risks associated with newborn male
      circumcision and less than one-third (31.1%) reported they would recommend the
      procedure when counseling parents. CONCLUSIONS: In 2008, only about one-third of
      the physicians surveyed thought that the benefits of male circumcision outweighed
      the risks and recommended it to parents of newborn sons. These attitudes may be
      relevant to the declining circumcision rates in the United States. Repeat surveys
      may be useful, given the new AAP and ACOG recommendations.

PMID- 24899260
TI  - Viral loads among young HIV-infected men with early syphilis.
AB  - High rates of HIV coinfection among men with syphilis suggest HIV transmission
      opportunities due to biologic and behavioral risk synergy. We abstracted HIV
      viral loads for HIV-infected males aged 24 years or younger with a diagnosis of
      early syphilis (ES) in Maricopa County, Arizona, in order to evaluate HIV
      infectivity. During 2009 to 2012, there were 56 HIV-infected, ES cases meeting
      the age criteria, of whom 32 (57%) had a detectable viral load performed within 1
      year of syphilis diagnosis (median 21 000 copies/mL, range 130-302 844
      copies/mL). Only 4 (7%) of the 56 patients had an undetectable viral load (<100
      copies/mL) reported within a year of syphilis diagnosis. Twenty (36%) had no
      reported viral load or a viral load collected after 1 year of syphilis diagnosis.
      Among this group of young men coinfected with HIV and ES, many had detectable
      viral loads collected near the time of syphilis diagnosis, suggesting the
      potential for HIV transmission. 

PMID- 24899261
TI  - Gender Differences in Severity and Correlates of Depression Symptoms in People
      Living with HIV in Ontario, Canada.
AB  - This study investigates the differences in severity and correlates of depression
      symptoms among 1069 men and 267 women living with HIV in Ontario, Canada, who
      completed the 20-item Center for Epidemiologic Studies Depression Scale (CES-D).
      Women had higher CES-D scores than that of men (median [interquartile range]: 13
      [5-26] versus 9 [3-20], P=.0004). More women had total CES-D scores>15 (mild
      moderate depression; 44% versus 33%, P=.002) and >21 (severe depression; 31%
      versus 23%, P=.003). Unlike men, at age 40, women's scores increased yearly (0.4
      per increased year, P=.005). The distribution of scores differed by gender: There
      was no difference in the 10th percentile of depression scores, 0 (95% confidence
      interval [CI]: 1.0-1.0) but the 75th percentile of depression scores for women
      was 6 (95% CI: 2.0-10.0) points higher than that of men. Important gender
      differences exist in depression symptoms and in correlates of symptoms in people
      living with HIV.

PMID- 24899262
TI  - Autosomal dominant inheritance of rapidly progressive amyotrophic lateral
      sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene.
AB  - Mutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS)
      account for 4 - 5% of familial cases of amyotrophic lateral sclerosis (ALS). We
      describe the identification and in vitro cellular characterization of a genetic
      mutation in a family in which the index case, and subsequently her two children,
      each developed rapidly progressive ALS at a young age and died within a year of
      onset. Exome capture and sequencing revealed a mutation in the FUS gene
      consisting of a 2-bp deletion, c.1509_1510delAG, resulting in a predicted
      truncated protein, p.G504Wfs * 12, lacking the nuclear localization signal.
      Expression of this mutation in HEK293 and NSC-34 cells demonstrated severe
      cytoplasmic mislocalization of mutant FUS, and colocalization with stress
      granules when compared to wild-type, R521C and P525L mutant FUS. This study
      provides further evidence of a broad correlation between clinical severity of FUS
      related ALS and mislocalization of the protein to the cytoplasm.

PMID- 24899263
TI  - Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in
      EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.
AB  - For patients with advanced non-small cell lung adenocarcinoma that fail to
      respond to first-line chemotherapy and that do not involve epidermal growth
      factor receptor (EGFR) mutations, previous empirical analysis showed that a
      single second-line chemotherapy agent may be inadequate for the control of
      further tumor development. This study examines the combination of S-1 drugs and
      nedaplatin that has no cross-resistance to first-line treatments; 179 cases of
      IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first
      line chemotherapy were included, and these subjects did not have mutated EGFRs.
      In the present study, S-1 plus nedaplatin chemotherapy was better than standard
      second-line chemotherapy options in the treatment of advanced lung adenocarcinoma
      that did not involve EGFR mutations and that failed to respond to first-line
      chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be
      well tolerated, making this chemotherapy technique a potentially strong candidate
      for the treatment of advanced non-small-cell lung adenocarcinoma. 

PMID- 24899265
TI  - The emerging role of aquaporin 5 (AQP5) expression in systemic malignancies.

PMID- 24899264
TI  - Effect of c-erbB2 overexpression on prognosis in osteosarcoma: evidence from
      eight studies.
AB  - C-erbB2 (HER-2/neu) plays an important role in the progression of several types
      of cancer by increasing tumor growth, migration, invasion, and metastasis and is
      associated with poor disease prognosis. Numerous studies examining the
      relationship between c-erbB2 expression and prognostic impact in patients with
      osteosarcoma have yielded inconclusive results. We therefore conducted a meta
      analysis to provide a comprehensive evaluation of the prognostic role of c-erbB2
      expression on 5-year survival, which compared the positive and negative
      expression of c-erbB2 in patients of the available studies. A detailed search was
      made in PubMed for relevant original articles published in English. Finally, a
      total of eight studies with 411 osteosarcoma patients were involved to estimate
      the relationship between c-erbB2 expression and 5-year overall survival. Positive
      expressions of c-erbB2 predicted poorer survival in osteosarcoma with the pooled
      RR of 1.53 (95 % CI 1.20-1.94, P = 0.0006). In conclusion, the findings from this
      present meta-analysis suggest that c-erbB2 overexpression is related to poor
      prognostic of osteosarcoma and can be a useful clinical prognostic factor for
      those patients.

PMID- 24899266
TI  - PLCgamma1-PKCgamma signaling-mediated Hsp90alpha plasma membrane translocation
      facilitates tumor metastasis.
AB  - The 90-kDa heat shock protein (Hsp90alpha) has been identified on the surface of
      cancer cells, and is implicated in tumor invasion and metastasis, suggesting that
      it is a potentially important target for tumor therapy. However, the regulatory
      mechanism of Hsp90alpha plasma membrane translocation during tumor invasion
      remains poorly understood. Here, we show that Hsp90alpha plasma membrane
      expression is selectively upregulated upon epidermal growth factor (EGF)
      stimulation, which is a process independent of the extracellular matrix.
      Abrogation of EGF-mediated activation of phospholipase (PLCgamma1) by its siRNA
      or inhibitor prevents the accumulation of Hsp90alpha at cell protrusions.
      Inhibition of the downstream effectors of PLCgamma1, including Ca(2+) and protein
      kinase C (PKCgamma), also blocks the membrane translocation of Hsp90alpha, while
      activation of PKCgamma leads to increased levels of cell-surface Hsp90alpha.
      Moreover, overexpression of PKCgamma increases extracellular vesicle release, on
      which Hsp90alpha is present. Furthermore, activation or overexpression of
      PKCgamma promotes tumor cell motility in vitro and tumor metastasis in vivo,
      whereas a specific neutralizing monoclonal antibody against Hsp90alpha inhibits
      such effects, demonstrating that PKCgamma-induced Hsp90alpha translocation is
      required for tumor metastasis. Taken together, our study provides a mechanistic
      basis for the role for the PLCgamma1-PKCgamma pathway in regulating Hsp90alpha
      plasma membrane translocation, which facilitates tumor cell motility and promotes
      tumor metastasis.

PMID- 24899267
TI  - In vitro mechanical testing of braided polyurethane elastic fiber and braided
      polyester for equine laryngoplasty.
AB  - OBJECTIVES: In vitro comparison of the mechanical properties of braided
      polyurethane elastomer (Lycra(r)) and braided polyester (EthibondTM) (1) when
      inserted into the muscular process of the arytenoid cartilage and (2) as suture
      loops. STUDY DESIGN: Experimental. ANIMALS: Equine cadaver larynges (n = 15).
      METHODS: The muscular processes (n = 30) of the arytenoid cartilages were
      dissected from each larynx and embedded in a resin base. Lycra(r) and EthibondTM
      prostheses were randomly allocated to the left or right muscular process and each
      underwent cyclic fatigue (25-50 N) followed by load-to-failure testing. Isolated
      suture loops of Lycra(r) (n = 25) and EthibondTM (n = 25) also underwent the same
      cyclic fatigue followed by load-to-failure testing (n = 20) or a creep testing
      protocol (25 N for 10 min; n = 5). RESULTS: Lycra(r) prostheses pulled through
      the cartilage in a significantly greater proportion of cyclic tests (P = .015)
      and at lower mean (+/-SD) loads, (95.9 +/- 23.4 N) during load-to-failure testing
      than EthibondTM prostheses (155.2 +/- 24.4 N; P = .0041). Lycra(r) had a
      significantly greater displacement with and without a cartilage interface when
      compared to EthibondTM (P < .001, P < .002). The Lycra(r) isolated suture loops
      failed at significantly greater loads (233.0 +/- 38.7 N) during load-to-failure
      testing than EthibondTM loops (201.6 +/- 47.4 N; P = .042). CONCLUSIONS: Lycra(r)
      prostheses embedded in laryngeal cartilage pulled through the cartilage at lower
      loads than EthibondTM prostheses. Lycra(r) suture loops were stronger than
      EthibondTM suture loops. Lycra(r) had greater displacement than EthibondTM in all
      tests as suture loops or when embedded in cartilage.

PMID- 24899268
TI  - Surgical vs medical treatments for type 2 diabetes mellitus: a randomized
      clinical trial.
AB  - IMPORTANCE: Many questions remain unanswered about the role of bariatric surgery
      for people with type 2 diabetes mellitus (T2DM). OBJECTIVE: To determine
      feasibility of a randomized clinical trial (RCT) and compare initial outcomes of
      bariatric surgery and a structured weight loss program for treating T2DM in
      participants with grades I and II obesity. DESIGN, SETTING, AND PARTICIPANTS: A
      12-month, 3-arm RCT at a single center including 69 participants aged 25 to 55
      years with a body mass index (calculated as weight in kilograms divided by height
      in meters squared) of 30 to 40 and T2DM. INTERVENTIONS: Roux-en-Y gastric bypass
      (RYGB), laparoscopic adjustable gastric banding (LAGB), and an intensive
      lifestyle weight loss intervention (LWLI). MAIN OUTCOMES AND MEASURES: Primary
      outcomes in the intention-to-treat cohort were feasibility and effectiveness
      measured by weight loss and improvements in glycemic control. RESULTS: Of 667
      potential participants who underwent screening, 69 (10.3%) were randomized. Among
      the randomized participants, 30 (43%) had grade I obesity, and 56 (81%) were
      women. Mean (SD) age was 47.3 (6.4) years and hemoglobin A1c level, 7.9% (2.0%).
      After randomization, 7 participants (10%) refused to undergo their allocated
      intervention (3 RYGB, 1 LAGB, and 3 LWLI), and 1 RYGB participant was excluded
      for current smoking. Twenty participants underwent RYGB; 21, LAGB; and 20, LWLI,
      with 12-month retention rates of 90%, 86%, and 70%, respectively. In the
      intention-to-treat cohort with multiple imputation for missing data, RYGB
      participants had the greatest mean weight loss from baseline (27.0%; 95% CI, 30.8
      23.3) compared with LAGB (17.3%; 95% CI, 21.1-13.5) and LWLI (10.2%; 95% CI, 14.8
      5.61) (P < .001). Partial and complete remission of T2DM were 50% and 17%,
      respectively, in the RYGB group and 27% and 23%, respectively, in the LAGB group
      (P < .001 and P = .047 between groups for partial and complete remission), with
      no remission in the LWLI group. Significant reductions in use of antidiabetics
      occurred in both surgical groups. No deaths were noted. The 3 serious adverse
      events included 1 ulcer treated medically in the RYGB group and 2
      rehospitalizations for dehydration in the LAGB group. CONCLUSIONS AND RELEVANCE:
      This study highlights several potential challenges to successful completion of a
      larger RCT for treatment of T2DM and obesity in patients with a body mass index
      of 30 to 40, including the difficulties associated with recruiting and
      randomizing patients to surgical vs nonsurgical interventions. Preliminary
      results show that RYGB was the most effective treatment, followed by LAGB for
      weight loss and T2DM outcomes at 1 year. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01047735.

PMID- 24899270
TI  - Big Bang blunder bursts the multiverse bubble.

PMID- 24899269
TI  - Duplication in the microtubule-actin cross-linking factor 1 gene causes a novel
      neuromuscular condition.
AB  - Spectrins and plakins are important communicators linking cytoskeletal components
      to each other and to cellular junctions. Microtubule-actin cross-linking factor 1
      (MACF1) belongs to the spectraplakin family and is involved in control of
      microtubule dynamics. Complete knock out of MACF1 in mice is associated with
      developmental retardation and embryonic lethality. Here we present a family with
      a novel neuromuscular condition. Genetic analyses show a heterozygous duplication
      resulting in reduced MACF1 gene product. The functional consequence is affected
      motility observed as periodic hypotonia, lax muscles and diminished motor skills,
      with heterogeneous presentation among the affected family members. To corroborate
      these findings we used RNA interference to knock down the VAB-10 locus containing
      the MACF1 homologue in C. elegans, and we could show that this also causes
      movement disturbances. These findings suggest that changes in the MACF1 gene is
      implicated in this neuromuscular condition, which is an important observation
      since MACF1 has not previously been associated with any human disease and thus
      presents a key to understanding the essential nature of this gene. 

PMID- 24899282
TI  - Phage therapy gets revitalized.

PMID- 24899283
TI  - Land models put to climate test.

PMID- 24899284
TI  - Funding windfall rescues abandoned stem-cell trial.

PMID- 24899285
TI  - Federal boost for German science.

PMID- 24899286
TI  - Big Bang finding challenged.

PMID- 24899288
TI  - Solar energy: Springtime for the artificial leaf.

PMID- 24899289
TI  - Alzheimer's disease: The forgetting gene.

PMID- 24899293
TI  - Biodiversity data: Mine centuries-old citizen science.

PMID- 24899294
TI  - History: Moon mapped by an artist's impression.

PMID- 24899295
TI  - Preclinical research: Design animal studies better.

PMID- 24899297
TI  - Laboratory training: Experimentation needs theory, too.

PMID- 24899296
TI  - Technology: Investment suggests RNAi is on the up.

PMID- 24899298
TI  - Gerald Guralnik (1936-2014).

PMID- 24899300
TI  - Astrophysics: The MAD world of black holes.

PMID- 24899299
TI  - Cell biology: Short RNAs and shortness of breath.

PMID- 24899301
TI  - Hepatitis C: Treatment triumphs.

PMID- 24899302
TI  - Neurological disorders: Quality-control pathway unlocked.

PMID- 24899303
TI  - Lipids in health and disease.

PMID- 24899304
TI  - Lipid landscapes and pipelines in membrane homeostasis.
AB  - The lipid composition of cellular organelles is tailored to suit their
      specialized tasks. A fundamental transition in the lipid landscape divides the
      secretory pathway in early and late membrane territories, allowing an adaptation
      from biogenic to barrier functions. Defending the contrasting features of these
      territories against erosion by vesicular traffic poses a major logistical
      problem. To this end, cells evolved a network of lipid composition sensors and
      pipelines along which lipids are moved by non-vesicular mechanisms. We review
      recent insights into the molecular basis of this regulatory network and consider
      examples in which malfunction of its components leads to system failure and
      disease. 

PMID- 24899305
TI  - Sphingolipid metabolites in inflammatory disease.
AB  - Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes.
      Progress in our understanding of sphingolipid metabolism, state-of-the-art
      sphingolipidomic approaches and animal models have generated a large body of
      evidence demonstrating that sphingolipid metabolites, particularly ceramide and
      sphingosine-1-phosphate, are signalling molecules that regulate a diverse range
      of cellular processes that are important in immunity, inflammation and
      inflammatory disorders. Recent insights into the molecular mechanisms of action
      of sphingolipid metabolites and new perspectives on their roles in regulating
      chronic inflammation have been reported. The knowledge gained in this emerging
      field will aid in the development of new therapeutic options for inflammatory
      disorders. 

PMID- 24899306
TI  - Sphingolipid lysosomal storage disorders.
AB  - Lysosomal storage diseases are inborn errors of metabolism, the hallmark of which
      is the accumulation, or storage, of macromolecules in the late endocytic system.
      They are monogenic disorders that occur at a collective frequency of 1 in 5,000
      live births and are caused by inherited defects in genes that mainly encode
      lysosomal proteins, most commonly lysosomal enzymes. A subgroup of these diseases
      involves the lysosomal storage of glycosphingolipids. Through our understanding
      of the genetics, biochemistry and, more recently, cellular aspects of
      sphingolipid storage disorders, we have gained insights into fundamental aspects
      of cell biology that would otherwise have remained opaque. In addition, study of
      these disorders has led to significant progress in the development of therapies,
      several of which are now in routine clinical use. Emerging mechanistic links with
      more common diseases suggest we need to rethink our current concept of disease
      boundaries. 

PMID- 24899307
TI  - The different shades of fat.
AB  - Our understanding of adipose tissue biology has progressed rapidly since the turn
      of the century. White adipose tissue has emerged as a key determinant of healthy
      metabolism and metabolic dysfunction. This realization is paralleled only by the
      confirmation that adult humans have heat-dissipating brown adipose tissue, an
      important contributor to energy balance and a possible therapeutic target for the
      treatment of metabolic disease. We propose that the development of successful
      strategies to target brown and white adipose tissues will depend on
      investigations that elucidate their developmental origins and cell-type-specific
      functional regulators. 

PMID- 24899308
TI  - The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes.
AB  - Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin
      resistance and type 2 diabetes, are rapidly growing epidemics, which lead to
      increased morbidity and mortality rates, and soaring health-care costs.
      Developing interventions requires a comprehensive understanding of the mechanisms
      by which excess hepatic lipid develops and causes hepatic insulin resistance and
      type 2 diabetes. Proposed mechanisms implicate various lipid species,
      inflammatory signalling and other cellular modifications. Studies in mice and
      humans have elucidated a key role for hepatic diacylglycerol activation of
      protein kinase Cepsilon in triggering hepatic insulin resistance. Therapeutic
      approaches based on this mechanism could alleviate the related epidemics of non
      alcoholic fatty liver disease and type 2 diabetes. 

PMID- 24899311
TI  - Dynamically important magnetic fields near accreting supermassive black holes.
AB  - Accreting supermassive black holes at the centres of active galaxies often
      produce 'jets'--collimated bipolar outflows of relativistic particles. Magnetic
      fields probably play a critical role in jet formation and in accretion disk
      physics. A dynamically important magnetic field was recently found near the
      Galactic Centre black hole. If this is common and if the field continues to near
      the black hole event horizon, disk structures will be affected, invalidating
      assumptions made in standard models. Here we report that jet magnetic field and
      accretion disk luminosity are tightly correlated over seven orders of magnitude
      for a sample of 76 radio-loud active galaxies. We conclude that the jet-launching
      regions of these radio-loud galaxies are threaded by dynamically important
      fields, which will affect the disk properties. These fields obstruct gas infall,
      compress the accretion disk vertically, slow down the disk rotation by carrying
      away its angular momentum in an outflow and determine the directionality of jets.

PMID- 24899315
TI  - A new 3D concentration gradient maker and its application in building hydrogels
      with a 3D stiffness gradient.
AB  - For a deeper knowledge of phenomena at cell and tissue level, for understanding
      the role on bimolecular signalling and for the development of new drugs it is
      important to recreate in vitro environments that mimic the physiological one.
      Spatial gradients of soluble species guide the cells' morphogenesis, and they
      range in a three-dimensional (3D) environment. Gradients of mechanical
      properties, which have a 3D pattern, could lead cell migration and
      differentiation. In this work, a new 3D Concentration Gradient Maker able to
      generate 3D concentration gradients of soluble species was developed, which could
      be used for differential perfusion of scaffolds. The same device can be applied
      to build hydrogel matrixes with a 3D gradient of mechanical properties.
      Computational dynamic fluid analysis was used to develop the gradient generator;
      the validation of the 3D gradient of stiffness was carried out using finite
      elements analysis and experimental studies. The device and its application could
      bring improvements in studying phenomena related to cell chemotaxis and
      mechanotaxis, but also to differentiation in the simultaneous presence of
      gradients in both soluble chemical species and substrate stiffness. Copyright (c)
      2014 John Wiley & Sons, Ltd.

PMID- 24899310
TI  - miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110.
AB  - The mir-34/449 family consists of six homologous miRNAs at three genomic loci.
      Redundancy of miR-34/449 miRNAs and their dominant expression in multiciliated
      epithelia suggest a functional significance in ciliogenesis. Here we report that
      mice deficient for all miR-34/449 miRNAs exhibited postnatal mortality,
      infertility and strong respiratory dysfunction caused by defective mucociliary
      clearance. In both mouse and Xenopus, miR-34/449-deficient multiciliated cells
      (MCCs) exhibited a significant decrease in cilia length and number, due to
      defective basal body maturation and apical docking. The effect of miR-34/449 on
      ciliogenesis was mediated, at least in part, by post-transcriptional repression
      of Cp110, a centriolar protein suppressing cilia assembly. Consistent with this,
      cp110 knockdown in miR-34/449-deficient MCCs restored ciliogenesis by rescuing
      basal body maturation and docking. Altogether, our findings elucidate conserved
      cellular and molecular mechanisms through which miR-34/449 regulate motile
      ciliogenesis. 

PMID- 24899309
TI  - Pro-resolving lipid mediators are leads for resolution physiology.
AB  - Advances in our understanding of the mechanisms that bring about the resolution
      of acute inflammation have uncovered a new genus of pro-resolving lipid mediators
      that include the lipoxin, resolvin, protectin and maresin families, collectively
      called specialized pro-resolving mediators. Synthetic versions of these mediators
      have potent bioactions when administered in vivo. In animal experiments, the
      mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance
      microbial clearance. Although they have been identified in inflammation
      resolution, specialized pro-resolving mediators are conserved structures that
      also function in host defence, pain, organ protection and tissue remodelling.
      This Review covers the mechanisms of specialized pro-resolving mediators and
      omega-3 essential fatty acid pathways that could help us to understand their
      physiological functions. 

PMID- 24899312
TI  - Membrane proteins bind lipids selectively to modulate their structure and
      function.
AB  - Previous studies have established that the folding, structure and function of
      membrane proteins are influenced by their lipid environments and that lipids can
      bind to specific sites, for example, in potassium channels. Fundamental questions
      remain however regarding the extent of membrane protein selectivity towards
      lipids. Here we report a mass spectrometry approach designed to determine the
      selectivity of lipid binding to membrane protein complexes. We investigate the
      mechanosensitive channel of large conductance (MscL) from Mycobacterium
      tuberculosis and aquaporin Z (AqpZ) and the ammonia channel (AmtB) from
      Escherichia coli, using ion mobility mass spectrometry (IM-MS), which reports gas
      phase collision cross-sections. We demonstrate that folded conformations of
      membrane protein complexes can exist in the gas phase. By resolving lipid-bound
      states, we then rank bound lipids on the basis of their ability to resist gas
      phase unfolding and thereby stabilize membrane protein structure. Lipids bind non
      selectively and with high avidity to MscL, all imparting comparable stability;
      however, the highest-ranking lipid is phosphatidylinositol phosphate, in line
      with its proposed functional role in mechanosensation. AqpZ is also stabilized by
      many lipids, with cardiolipin imparting the most significant resistance to
      unfolding. Subsequently, through functional assays we show that cardiolipin
      modulates AqpZ function. Similar experiments identify AmtB as being highly
      selective for phosphatidylglycerol, prompting us to obtain an X-ray structure in
      this lipid membrane-like environment. The 2.3 A resolution structure, when
      compared with others obtained without lipid bound, reveals distinct
      conformational changes that re-position AmtB residues to interact with the lipid
      bilayer. Our results demonstrate that resistance to unfolding correlates with
      specific lipid-binding events, enabling a distinction to be made between lipids
      that merely bind from those that modulate membrane protein structure and/or
      function. We anticipate that these findings will be important not only for
      defining the selectivity of membrane proteins towards lipids, but also for
      understanding the role of lipids in modulating protein function or drug binding. 

PMID- 24899317
TI  - Potential of global health education in low-income settings.

PMID- 24899316
TI  - Induction of serpinb1a by PACAP or NGF is required for PC12 cells survival after
      serum withdrawal.
AB  - PC12 cells are used to study the signaling mechanisms underlying the neurotrophic
      and neuroprotective activities of pituitary adenylate cyclase-activating
      polypeptide (PACAP) and nerve growth factor (NGF). Previous microarray
      experiments indicated that serpinb1a was the most induced gene after 6 h of
      treatment with PACAP or NGF. This study confirmed that serpinb1a is strongly
      activated by PACAP and NGF in a time-dependent manner with a maximum induction (~
      50-fold over control) observed after 6 h of treatment. Co-incubation with PACAP
      and NGF resulted in a synergistic up-regulation of serpinb1a expression (200-fold
      over control), suggesting that PACAP and NGF act through complementary
      mechanisms. Consistently, PACAP-induced serpinb1a expression was not blocked by
      TrkA receptor inhibition. Nevertheless, the stimulation of serpinb1a expression
      by PACAP and NGF was significantly reduced in the presence of extracellular
      signal-regulated kinase, calcineurin, protein kinase A, p38, and PI3K inhibitors,
      indicating that the two trophic factors share some common pathways in the
      regulation of serpinb1a. Finally, functional investigations conducted with siRNA
      revealed that serpinb1a is not involved in the effects of PACAP and NGF on PC12
      cell neuritogenesis, proliferation or body cell volume but mediates their ability
      to block caspases 3/7 activity and to promote PC12 cell survival.

PMID- 24899318
TI  - Prevalence and correlates of cervico-vaginal clinical syndromes among women
      attending a health camp in Lalitpur district of Nepal.
AB  - BACKGROUND: Sexual and reproductive health of women is a major public health
      problem in Nepal. Screening of cervico-vaginal clinical syndromes could
      potentially provide insights to the prevalence of sexually transmitted infections
      (STIs), which is not known. OBJECTIVE: To investigate the prevalence and factors
      associated with cervico-vaginal clinical syndromes in the socio-behavioral,
      medical, and public health context of Nepal. METHODS: Married women attending a
      clinical health camp held by the Nepal Fertility Care Centerin Khokana of
      Lalitpur district were recruited to the study. Seventy-three participants
      completed face-to-face questionnaires on basic socio-demographic, behavioral and
      reproductive health factors and underwent pelvic screening including clinical
      diagnosis of cervicitis and vaginitis. An univariate analysis was performed to
      determine if any of the self-reported variables were associated with abnormal
      pelvic examination (cervicitis and/or vaginitis). RESULTS: Vaginitis was
      diagnosed in three (4.4%) participants, while cervicitis was detected in 16
      (23.5%) women. None of the participants reported any high risk sexual behavior.
      However, 28% of the participants reported having had STI diagnosis in the past
      and was associated (P<0.008) with abnormal pelvic results. Additionally, women
      with lower education were associated (p<0.02) with abnormal pelvic results.
      CONCLUSIONS: The high occurrence of cervicitis in our exploratory could indicate
      the high prevalence of STIs. However, while there could potentially be an unknown
      epidemic of STIs related to the clinical syndromes, point of care testing
      practice might help to understand the true prevalence of STIs in Nepali women and
      also reduce the health burden and consequences of over treatment based on the
      current symptomatic diagnosis.

PMID- 24899319
TI  - Evaluation of matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of
      metalloproteinases-2 (TIMP-2) in oral submucous fibrosis and their correlation
      with disease severity.
AB  - BACKGROUND: Oral submucous fibrosis (OSF), a potentially malignant oral lesion,
      is a form of pathological fibrosis affecting the oral mucosa. It results from an
      imbalance in equilibrium of the normal process of synthesis and degradation of
      extra cellular matrix. Matrix metalloproteinases and its inhibitors play
      important role in remodeling of the extra cellular matrix which are important in
      progression and pathogenesis of potentially malignant lesions to malignancy.
      OBJECTIVES: To evaluate the expression and distribution of Matrix
      metalloproteinases-2 (MMP- 2) and Tissue inhibitor of metalloproteinases-2 (TIMP
      2) in different grades of Oral Submucous Fibrosis(OSF). METHOD:
      Immunohistochemical analysis for MMP-2 and its TIMP-2 was performed in 30
      histopathologically confirmed, formalin fixed, paraffin embedded specimens of
      OSF. A semi-quantitative analysis was done to assess the expression, distribution
      and comparison of these in various stages of this disease. RESULT: All moderately
      advanced cases and 64.2% for MMP-2 and 78.5% for TIMP-2 of early stage cases
      showed positivity. Between two stages of OSF, statistically significant
      differences were noted in expression of TIMP-2 in lamina propria, deep connective
      tissue and supra basal layers (p<0.05) and basal and supra basal layers for MMP-2
      (p<0.05). CONCLUSION: The simultaneous increase in expression of MMP-2 and TIMP-2
      with advancing stages of OSF can provide a basis for considering the proteases as
      important mediators in the pathogenesis and progression of OSF which could aid in
      identifying the aggressiveness of the condition and elucidate its role in its
      malignant transformation.

PMID- 24899320
TI  - Nuchal translucency in normal fetus and its variation with increasing crown rump
      length (CRL) and gestational age.
AB  - BACKGROUND: Nuchal translucency (NT) is the fluid collection behind the fetal
      neck which can be measured by ultrasound at 11-14 weeks of gestation. Increase in
      the nuchal translucency thickness is associated with various congenital
      anomalies. OBJECTIVE: To study the relationship between nuchal translucency
      thickness, crown rump length and gestational age in normal fetus. METHODS:
      Prospective analytical study conducted on 211 pregnant women from March 2011 to
      August 2012. Measurement of Nuchal translucency thickness and crown rump length
      was performed by ultrasound at 11-14 weeks of gestation. The relationship between
      nuchal translucency thickness, crown rump length and gestational age was studied
      by using linear regression analysis. RESULTS: The mean CRL was 63.67+13.48mm
      (range 41.2-88mm) and mean NT thickness was 1.55+0.35mm (range 0.8-2.7mm),
      respectively. The median gestational age was 12.9 weeks. The regression equation
      which shows relation between median NT thickness and CRL was described as
      follows: expected NT thickness = 0.013CRL+0.725, (R2 = 0.258, p <0.001). There
      was increase in the incidence of NT thickness more than or equal to 2.5mm; 1.7%
      in fetus between 12-12.9 weeks of gestation to 15.1% in fetus between 14.0-14.9
      weeks. CONCLUSION: Our study offers normative data of NT thickness in normal
      fetus, which can be used as reference to screen various chromosomal and
      congenital abnormalities between 11- 14 weeks of gestation. NT thickness
      increased with increasing CRL and a false positive rate increases with increasing
      gestational age.

PMID- 24899321
TI  - Comparative study of hyperbaric bupivacaine plus ketamine vs bupivacaine plus
      fentanyl for spinal anaesthesia during caeserean section.
AB  - BACKGROUND: Spinal anesthesia is widely used for caesarean section due to its
      rapid onset, low failure rate, complete analgesia. Addition of intrathecal
      ketamine and opioids to local anaesthetics seems to improve the quality of block
      and prolong the duration of analgesia. OBJECTIVES: The purpose of this study was
      to compare the effect of intrathecal ketamine mixed with hyperbaric bupivacaine
      to intrathecal fentanyl mixed with hyperbaric bupivacaine. METHODS: One hundred
      parturients ASA Grade I scheduled for elective or semiurgent caesarean section
      under spinal anaesthesia were randomly divided into two groups. Group A received
      2ml (10 mg) hyperbaric bupivacaine 0.5% plus 25 mg preservative free ketamine.
      Group B received 2ml (10mg) hyperbaric bupivacaine 0.5% plus 25MUg fentanyl. The
      patients were observed intraoperatively for the onset of sensory block, degree of
      motor block and total duration of analgesia. RESULTS: The time to achieve Bromage
      scale 3 motor blockade was shorter in Group A than in Group B.(p= 0.445) whereas
      time to achieve highest dermatomal level of sensory block was shorter in Group A
      than in Group B (p= 0.143). The duration of spinal analgesia was longer in Group
      B than in Group A (p= 0.730). The frequency of side effect such as sedation score
      was higher in Group A compared to Group B (p= 0.048). The incidence of pruritus
      was significantly higher in Group B compared to Group A (p = 0.000). CONCLUSION:
      Addition of preservative free ketamine lead to faster onset of sensory and motor
      blockade, although it did not prolong the duration of spinal analgesia compared
      to addition of fentanyl in parturients undergoing caesarean section with spinal
      anaesthesia.

PMID- 24899323
TI  - The correlation between fine needle aspiration cytology and histopathology of
      head and neck lesions in Kathmandu University Hospital.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) with it's minimally
      invasiveness has been a well accepted procedure in the initial diagnosis of
      various swellings. With time and experience high sensitivity and specificity of
      FNAC over conventional open biopsy has lead to the wide acceptance of this
      procedure. OBJECTIVE: To evaluate the utility of aspiration cytology as a first
      line diagnostic tool in palpable head and neck masses and correlate with
      histologic results for evaluating diagnostic accuracy. METHODS: A hospital based
      prospective, comparative study was conducted among patients with various
      swellings at Head and Neck regions in the Department of Pathology, Dhulikhel
      Hospital between July 2011 to June 2012. FNAC were done from the palpable masses
      of head and neck regions and were compared with biopsy findings of the same
      lesions. Data entry and analysis performed using SPSS version 16. The
      sensitivity, specificity and accuracy rates were calculated. RESULTS: A total 64
      patients were subjected to both FNAC and histopathological examination (HPE).
      Total 39 (61 %) were females and 25 (39 %) were males with M: F ratio of 1:1.6.
      The age group ranged from 9 to 80 years. Twenty five percent of patients were in
      the age group below 20 years. The highest number of cases included lymph nodes 29
      (45%) followed by thyroid 24(37.5 %), salivary glands 10(16%) and 1 case (1.6%)
      was a soft tissue swelling over the occipital region. Highest sensitivity,
      specificity and accuracy rate for diagnosis by FNAC were observed in thyroid. The
      overall sensitivity and specificity of FNAC were 86% and 97% respectively in
      determining the various pathologies. The overall accuracy of FNAC in present
      study was 87.4%. CONCLUSION: FNAC is a minimally invasive first line
      investigation with a high sensitivity and specificity for the diagnosis of
      various head and neck lesions.

PMID- 24899322
TI  - Urinary bladder carcinoma: impact of smoking, age and its clinico-pathological
      spectrum.
AB  - BACKGROUND: Urinary bladder carcinoma is common urological malignancy. Although
      epidemiological evidence favors role of occupational exposure to chemical
      carcinogen as the aetiological factor of bladder carcinoma, many cases arise with
      no obvious occupational exposure to chemical carcinogen. Tobacco and cigarette
      smoking is common in both rural and urban areas of Nepal. OBJECTIVE: The
      objective of this study was to determine the impact of smoking and age in urinary
      bladder carcinoma with related clinicopathological correlations. METHOD: A total
      of 56 (44 males and 12 females) cases of urinary bladder cancer treated at
      Dhulikhel Hospital, Kathmandu University Teaching Hospital during time period of
      January 2004 to December 2013 were included in the study. Data of patients with
      Urinary bladder cancer were obtained from hospital records and evaluated for age,
      sex, history of smoking, clinical presentations, cystoscopic findings and
      histopathological characteristics. RESULTS: Out of 56 cases, 51 (91.1%) of the
      patients had hematuria. History of smoking was found in 44 patients. Smoking was
      found much higher in males (88%) than females (41.66%). Transitional cell
      carcinoma (TCC) was the most common histological variety, which was seen in 51
      (91.07%) patients. The significant impact of smoking was found in terms of grade
      of TCC. CONCLUSION: The incidence of bladder carcinoma is higher in male and TCC
      is the most common variety of Urinary bladder malignancy. History of smoking
      correlated with grade.

PMID- 24899324
TI  - The predictive value of pre-operative symptoms including upper gastrointestinal
      endoscopy before laparoscopic cholecystectomy for elective symptomatic
      cholecystolithiasis.
AB  - BACKGROUND: It has always been a challenge to distinguish between upper
      gastrointestinal symptoms due to gall stones or any other causes. The persistence
      of abdominal symptoms even after cholecystectomy is highly discouraging for
      surgeons. OBJECTIVE: To evaluate the value of preoperative (UGE) as a routine
      investigative tool in patients with gall stone disease and to assess the outcome
      of cholecystectomy in patients with gallstones on preoperative abdominal
      symptoms. METHODS: This is a prospective study conducted on 96 cases at the
      Department of Surgery, Dhulikhel Hospital among ultrasonographically proven gall
      bladder stones irrespective of age and sex. After the examination, all the
      patients were subjected to UGE, and biopsy were obtained for histopathology if
      required. The statistical analysis were performed using spss version 16. RESULTS:
      Out of total patients, 84(87.5%) were females and 12(12.5%) were males with a M:
      F ratio of 1:7. Both the sexes were comparable in age groups. Out of total 96
      patients, 53(55.2%) presented with typical pain and 43(44.8%) presented with
      atypical pain. All the patients were subjected to upper gastrointestinal
      endoscopy (UGE) and 53(55.2%) had normal findings and 43(44.8%) had various
      lesions. Patients with typical pattern of pain had normal endoscopic findings and
      those with atypical pain had pathology in upper gastroendoscopy (p<0.001).
      Serious pathology resulting to change of the planned treatment was found in three
      cases (3.12%). Among them two had gastric carcinoma and one had active peptic
      ulcer disease. The relief rate after the cholecystectomy was significant in
      patients with typical pain than among those with atypical pain (p<0.001). The
      commenest post cholecystectomy symptoms were heart burn (10%), abdominal
      discomfort (9%) and dyspepsia (7%). CONCLUSION: Presence of atypical pain in
      patients with gall stones is highly likely to have other coexisting upper
      gastrointestinal pathologies. Hence, upper gastrointestinal endoscopy prior to
      elective cholecystectomy in patients with gall stones can be clinically helpful.

PMID- 24899325
TI  - Clinicoradiologic evaluation of Eagle's syndrome and its management.
AB  - BACKGROUND: Eagle's syndrome (Elongated styloid process) is often misdiagnosed
      due to its vague symptomatology. The diagnosis relies on detail history taking,
      palpation of styloid process in tonsillar fossa and imaging modalities.
      OBJECTIVE: To assess the length and medial angulation of elongated styloid
      process with the help of three dimensional computed tomography (3D CT) scan and
      to describe our clinical and surgical experience with patients suffering from
      Eagle's syndrome. METHOD: Prospective, analytical study conducted from August
      2011 to August 2012 among 39 patients with Eagle's syndrome. Detailed history
      taking, clinical examination and 3D CT scan was performed. Length and medial
      angulation was calculated. Patients with styloid process length longer than 2.50
      cm underwent surgical excision via intraoral approach. Medial angulation of
      styloid process on both sides was correlated with each other using rank
      correlation coefficient. Wilcoxon Signed Rank test was applied to test
      significant difference between pre-operative and postoperative symptoms scores.
      RESULT: Significant positive correlation was found between the medial angulation
      of styloid process on right side and left side (? =0.81, p<0.001). Significant
      difference was also observed between pre and post-operative symptoms scores (z=
      5.16, p<0.001) . CONCLUSION: Possibility of Eagle's syndrome should always be
      considered while examining patients with vague neck pain. 3D CT reconstruction is
      a gold standard investigation which helps in studying the relation of styloid
      process with surrounding structures along with accurate measurement of its length
      and medial angulation.

PMID- 24899326
TI  - Comparision of clinical and laboratory parameters in culture proven and unproven
      early onset sepsis in NICU.
AB  - BACKGROUND: Early onset sepsis remains a major cause for neonatal morbidity and
      mortality. OBJECTIVES: The aim of this study was to describe and compare the
      clinical and laboratory characteristics of neonates in neonatal intensive care
      unit with culture positive and negative early onset sepsis and verify if there
      were any differences between the groups. METHODS: A one year comparative
      prospective study was conducted from January 2011 to January 2012 in neonatal
      intensive care unit (NICU), Dhulikhel Hospital, Kathmandu University Hospital
      (KUH). RESULTS: Out of 215 cases of suspected neonatal sepsis, 192 (89.30%) cases
      of early onset sepsis were admitted in neonatal intensive care unit. Out of which
      82 cases (42.7%) had blood culture positive and 110( 57.3%) had culture negative
      but compatible with features of clinical sepsis. There were no cases of culture
      proven meningitis and urinary tract infections. The clinical characteristic did
      not show any statistical differences between the study groups except for seizure
      which was found to be high in culture positive cases (p= 0.041). The hospital
      stay in neonatal intensive care unit was significantly longer (p=0.02) in culture
      positive cases. As for the laboratory test there were no differences found
      between the two study groups except cases of meningitis was more in culture
      proven early onset sepsis (p=0.00). The overall mortality in early onset sepsis
      was 36.95%. The higher mortality of 64.7% was seen in culture positive cases but
      statistically not significant. CONCLUSION: Clinical manifestation and laboratory
      test were insufficient to distinguish between neonatal infection with blood
      culture positive and negative sepsis, hence both culture positive and negative
      cases should be treated promptly and equally.

PMID- 24899327
TI  - Variation of carrying angle with age, sex, height and special reference to side.
AB  - BACKGROUND: The carrying angle is defined as the acute angle made by the median
      axis of arm and median axis of forearm in full extension and supination. This
      angle permits the forearms to clear the hips in swinging movements during walking
      and is important when carrying objects. OBJECTIVE: The purpose of this study was
      to determine the values of carrying angle in both the sexes according to the age
      group in relation with height and special reference to side. METHODS: To evaluate
      the elbow carrying angle in normal children between 5-15 years by a manual
      goniometer, measurements were performed in 532 children (Male- 335, Female- 197),
      with the elbow in full extension and forearm in supination. Carrying angle was
      measured on right and left upper limbs to find out the difference on both the
      limbs. Their height, ages and sexes are also recorded. Bicipital groove, biceps
      brachii tendon at its insertion and palmaris longus tendon at the wrist were
      palpated and marked as anatomical landmarks to demarcate the median axes of arm
      and forearm respectively. RESULTS: The mean carrying angle of male on the left
      limb was 7.0359 degrees  and the female was 7.8030 degrees  and the mean carrying
      angle of male on the right limb was 4.5509 degrees  and the female was 4.9545
      degrees . We observed the greater carrying angle in non-dominant limb than the
      dominant limbs. There was significant positive correlation between height of
      students and carrying angle left (r =0.0866, p= 0.048<0.05), negative correlation
      between height and carrying angle right (r= -0.082, p= 0.058 >0.05). CONCLUSION:
      The present study showed that the carrying angle was greater in female than in
      male and was greater in non-dominant arm than in dominant arm and the carrying
      angle was not inversely related to the height of the person.

PMID- 24899328
TI  - Clinical profile and antibiotics sensitivity in childhood urinary tract infection
      at Dhulikhel Hospital.
AB  - BACKGROUND: Urinary Tract Infection implies presence of actively multiplying
      organisms in the urinary tract. Although it is infrequently associated with
      mortality, it is still a significant cause of morbidity. Early diagnosis is
      critical to preserve renal function of growing kidney. OBJECTIVE: Our purpose was
      to determine the clinical, microbiologic profile and antibiotic sensitivity of
      such infections in pediatric Urinary Tract Infection (UTI) patients at Dhulikhel
      Hospital. METHODS: A hospital based prospective descriptive study of 135 children
      from 2 months to 16 years, with clinical diagnosis of urinary tract infection who
      visited the pediatric department of Dhulikhel Hospital over the period of 15
      months were enrolled in the study. All patients underwent routine urine analysis
      and culture. Children with recurrent UTI underwent micturating cystourethrogram
      (MCUG). Children with recurrent UTI of more than two years and with feature of
      pyelonephritis underwent USG abdomen as well. Complications and response of the
      treatment was observed in all cases of UTI. All data were entered in Epidata and
      data analysis was done using spss 16 version. RESULTS: Among 135 children, 32.5%
      were male and 67.4% were female. Fever was the most common presenting symptom in
      74.80% of patients followed by dysuria in 54.1%. Among these children 95.6% had
      significant pyuria and 45% had culture positive infection. Children who showed
      positive for bacteriuria, Escherichia coli (78.7%) was the most common organism
      and are more than 80% sensitive to Amikacin, Gentamicin, Ceftriaxone, Ofloxacin,
      Nalidixic acid, Imipenem and Vancomycin. Co-trimoxazole was the most common drug
      used for treatment with a mean drug respond time of (mean+/-S.D) of 2.21+/-.78
      days. 2+/-. Children who had recurrent UTI were more prone to develop culture
      positive UTI (p=0.0001). CONCLUSION: Urinary Tract Infection in female was almost
      twice more common than in male. Cotrimoxazole was the most common drug used for
      treatment, sensitivity of this drug was less than 50% for all organisms.

PMID- 24899329
TI  - A study of assessment of partial edentulous patients based on Kennedy's
      classification at Dhulikhel Hospital Kathmandu University Hospital.
AB  - BACKGROUND: Oral health contributes significantly towards quality of life(QOL).
      Edentulousness falls in a special category among the various conditions of dental
      origin. Dietary intake and nutritional status is affected by poor oral health and
      loss of teeth. This will ultimately compromise general health. OBJECTIVE: To
      identify the frequency of Kennedy's classification among partial edentulous
      patients and to compare occurrence among gender and between upper and lower
      arches and also to compare edentulousness among employed and unemployed
      population. METHODS: This study was carried out at Dhulikhel Hospital Dental
      Department. The study was conducted randomly among 194 patients in dental OPD who
      were partially edentulous. A structured pro forma was used to find out the
      edentulousness based on Kennedy,s classification. RESULTS: Among the Kennedy's
      classification ClassIII was found to be most common. Among them females and
      unemployed group were found to have more edentulousness and upper arch was more
      common. It was also found that females were more conscious and get the
      replacement of missing teeth among which those having Class IV missing were
      replaced most often. CONCLUSION: The Kennedy Class III partial edentulousness
      type is most commonly found in this study.

PMID- 24899330
TI  - Custom milled zirconia implant supporting an ceramic zirconia restoration: a
      clinical report.
AB  - Dental implants constitute a well-established approach for replacement of lost
      teeth with titanium being the most favored material for implantation. However,
      titanium has its limitations in esthetically demanding cases and neither the form
      nor material of such implants has changed much over the past 40 years. Today,
      there is scientific evidence that zirconia dental implants osseointegrate well
      and offer many advantages over titanium implants. This report demonstrates the
      successful clinical use of a custom milled root analogue zirconia implant for
      single tooth replacement. A left maxillary first molar was removed, allowed to
      heal for four months and a custom-made, root-analogue, roughened zirconia was
      fabricated and placed. Subsequently it was restored with zirconia all ceramic
      crown. No complications occurred during the healing period. This successful case
      warrants further clinical research on zirconia custom milled implants in well
      controlled trials. 

PMID- 24899331
TI  - An interesting case of post traumatic tibialis anterior muscle herniation.
AB  - A muscle hernia is defined as a protrusion of the muscle belly through an
      acquired or congenital fascial defect. Muscle herniation through fascia is a
      relatively rare entity. Though predominantly asymptomatic, rarely they can be
      cause of vague pain in the leg, aggravated by exercises. Various conservative
      measures have been described for asymptomatic hernias, but treatment of
      symptomatic cases remains controversial. Here we present a case of symptomatic
      post traumatic tibialis anterior muscle herniation which was treated successfully
      with autologous fascia lata graft in Yenepoya Medical College, Mangalore in the
      month of January 2013. Muscle hernias should be kept in mind as a rare
      differential diagnosis whenever patients present with persisting vague leg pain
      with or without swelling. If conservative treatment fails, we recommend closure
      with autologous graft or fasciotomy to relieve the symptoms. 

PMID- 24899332
TI  - Pregnancy with hypertrophic cardiomyopathy--a potential risk factor for maternal
      mortality.
AB  - We report a case of a 21 year old married woman diagnosed to have severe
      hypertrophic cardiomyopathy at 12 weeks of gestation by echocardiograph at Lata
      Mangeshkar Hospital, Nagpur on 12th June, 2012. Her mother's and maternal uncle's
      sudden death at young age along with severe form of disease brought a lot of
      apprehension in the beginning considering the possible catastrophic effect of
      hemodynamic changes associated with pregnancy and labor. She was asymptomatic
      before pregnancy but developed dyspnoea on exertion during pregnancy and hence
      was started on calcium channel blocker verapamil. She remained asymptomatic
      throughout pregnancy and later underwent elective caesarean section at term under
      epidural anaesthesia for major cephalopelvic disproportion with uneventful
      postoperative course. Current data on pregnancy outcome in Hypertrophic
      cardiomyopathy are limited in Southasian countries despite its high prevalence in
      general population. This case report illustrates that with favourable clinical
      profile and specialist multidisciplinary team management women with hypertrophic
      cardiomyopathy tolerate pregnancy well with good outcome. 

PMID- 24899333
TI  - Endodontic management of radix paramolaris with six canals: a clinical case
      report.
AB  - Endodontic therapy of mandibular molars is a challenging task due to its varied
      root canal morphology. A mandibular first molar with additional buccal root
      (Radix paramolaris) and additional distolingual root (Radix Entomolaris) is an
      example of its varied anatomy. A successful management of atypical root canal
      configurations is an important aspect in determining the success rate of root
      canal therapy. The detail knowledge of the root morphology and canal anatomy
      allows the clinician for accurate location of the extra roots and canals and
      accordingly the refinement of the access cavity for the stress free entry of
      complex anatomy. Hence, for a successful root canal therapy, clinician must be
      aware of the external and internal anatomic variations .The aim of this clinical
      case report is to present and describe the unusual presence of two separate
      mesial roots and six root canals in mandibular first molar, detected during
      routine endodontic therapy. 

PMID- 24899334
TI  - Vertical gaze palsy with skew deviation.
AB  - With the advancement of neuroradiology, clinical localization followed by
      radiology, had made neurology more interesting. Vertical gage palsy as
      presentation cerebrovascular disease is not so common. Vertical gaze palsy
      usually localizes the lesion to dorsal mid brain. A 56 years male patient
      presented with sudden onset vertigo, diplopia, transient loss of consciousness
      and sways toward right side while walking. Clinical examination showed vertical
      gaze palsy with skew deviation along with swaying towards rt. during walk. MRI
      brain showed - infarct involving dorsal midbrain at superior colliculus level and
      medial thalamus. 

PMID- 24899335
TI  - Esthetics in removable partial denture--a review.
AB  - Removable partial denture is a repulsive modality of treatment that we still must
      rely upon for certain cases and is a part of the practice. But these patients
      expect it to look as esthetic as any other contemporary modality of treatment.
      This article thus focuses on the esthetic aspects that a clinician must place
      emphasis upon during the designing and fabrication of prosthesis to provide the
      desirable outcome. 

PMID- 24899336
TI  - Review of cesarean section on maternal request in a tertiary care institute;
      scenario in developing country.
AB  - Mother requesting of caesarean reflects a belief among society that elective
      caesarean safer than vaginal delivery in term of fetus and mother. Although the
      study data neglecting the facts other skewed part in this issue is consideration
      of resources, as in developing countries, where maternal mortality is still high
      due to lack of adequate resources. Mother coming to obstetrician with mother's
      request should individualize in every case considering mother's argument, society
      and evidence base guideline. 

PMID- 24899337
TI  - Blood transfusion in obstetrics.
AB  - Transfusion of blood and blood components is a common practice in obstetric wards
      but it is not without risk. The incidence of transfusion reactions varies from 4
      in every hundred transfusions for non-haemolytic reactions to one in every 40,000
      for haemolytic transfusion reactions. The physiological basis of blood
      transfusion is outlined in this article. Most of the donated blood is processed
      into components: packed red cells (PRBCs), platelets, and fresh frozen plasma
      (FFP) or cryoprecipitate. Various alternatives to blood transfusion exist and
      include autotransfusion, pre-autologous blood storage, use of oxygen carrying
      blood substitutes and intraoperative cell salvage. Despite the risks associated
      with transfusions, obstetricians are frequently too aggressive in transfusing
      blood and blood products to their patients. Acute blood loss in obstetrics is
      usually due to placenta praevia, postpartum blood loss and surgery related. An
      early involvement of a consultant obstetrician, anaesthetist, haematologist and
      the blood bank is essential. There are no established criteria for initiating red
      cell transfusions and the decision is purely based on clinical and haematological
      parameters, which have been discussed along with the general principles of blood
      transfusion in obstetrics and some practical guidelines. 

PMID- 24899338
TI  - Joint effusions and purpura in multiply-transfused adult beta-thalassemia-
      clinical pointers to diagnosis of scurvy.
AB  - Periodic transfusions and effective chelation have ensured that thalassemics
      survive in to adulthood but their life is punctuated by peculiar problems in
      adulthood. Three cases of scurvy are being reported presenting uniquely as
      purpura, right hip joint effusion and right knee joint effusion with haemorrhage
      in prepatellar and retropatellar bursae, respectively over an 18 month period
      (2009-2010). The first two cases did give a history of gum bleed. None had any
      coagulation disturbance or transfusion-transmitted infections or connective
      tissue disorder. All the three cases responded dramatically to vitamin C
      supplementation. It is imperative to keep in mind that recurrent blood
      transfusions are associated with a state of subclinical vitamin C deficiency and
      overt scurvy may manifest as cumulative number of transfusions increase, as in
      adult thalassemics. 

PMID- 24899339
TI  - Effectiveness of interventions to reduce flour dust exposures in supermarket
      bakeries in South Africa.
AB  - RATIONALE: A recent study of supermarket bakery workers in South Africa
      demonstrated that 25% of workers were sensitised to flour allergens and 13% had
      baker's asthma. Evidence on exposure reduction strategies using specifically
      designed interventions aimed at reducing the risk of baker's asthma is scarce.
      OBJECTIVES: The aim of this study was to evaluate the effectiveness of different
      control measures to reduce airborne flour dust exposure using a randomised
      design. METHODS: A group-randomised study design was used to assign 30 bakeries
      of a large supermarket chain store to two intervention groups and a control
      group, of which 15 bakeries were studied. Full-shift environmental personal
      samples were used to characterise exposure to flour dust and wheat and rye
      allergens levels pre-intervention (n=176) and post-intervention (n=208). RESULTS:
      The overall intervention effect revealed a 50% decrease in mean flour dust, wheat
      and rye allergen exposure. The reduction in exposure was highest for managers
      (67%) and bakers (47%), and lowest for counterhands (23%). For bakers, the
      greatest reduction in flour dust was associated with control measures such as the
      use of the mixer lid (67%), divider oil (63%) or focused training (54%). However,
      the greatest reduction (80%) was observed when using a combination of all control
      measures. CONCLUSIONS: A specially designed intervention strategy reduced both
      flour dust and allergen levels. Best results were observed when combining both
      engineering controls and training. Further studies will investigate the long-term
      health impact of these interventions on reducing the disease burden among this
      group of bakers.

PMID- 24899340
TI  - Outcomes Associated With Prothrombin Complex Concentrate for International
      Normalized Ratio Reversal in Patients on Oral Anticoagulants With Acute Bleeding.
AB  - BACKGROUND: Management of bleeding in patients on oral anticoagulants (OACs) is
      crucial in optimizing outcomes. No large studies examine 3-factor prothrombin
      complex concentrate (PCC) for OAC reversal. OBJECTIVE: To assess outcomes after
      administration of 3-factor PCC for reversal of international normalized ratio
      (INR). METHOD: We conducted an institutional review board-approved retrospective
      cohort study in all patients admitted to our level II trauma center over a 5-year
      period from 2007 to 2012 who received PCC for INR reversal and bleeding
      management. The primary outcome was assessment of efficacy as measured by
      achievement of INR < 1.5. Secondary objectives were to evaluate: factors
      associated with achievement of target INR, cessation of bleeding, mortality,
      outcome differences with or without fresh frozen plasma (FFP) or protocol
      utilization, safety, and cost. RESULT: A total of 403 patients were evaluated.
      Target INR was achieved in 88.8% of patients and was influenced by baseline INR.
      Associated factors were younger age (P = 0.02), utilization of the institution's
      protocol (P < 0.01), and concomitant administration of vitamin K (P < 0.01).
      Concomitant FFP did not affect achievement. Bleeding cessation occurred in 333
      (82.6%) patients, and 68 (16.9%) patients died. Patients who achieved target INR
      were more likely to have bleeding cessation (P < 0.01). The odds of survival for
      those who reached target INR was 3.8 times greater (P < 0.01). The incidence of
      thromboembolism was 3.7%. CONCLUSION: Three-factor PCC administration with IV
      vitamin K was effective for INR reversal and bleeding cessation and should
      continue to be a mainstay of therapy pending head-to-head outcome and cost
      comparisons with 4-factor products.

PMID- 24899343
TI  - An HLA-A*11 variant, A*11:166, revealed in a Taiwanese unrelated bone marrow
      hematopoietic stem cell donor.
AB  - One nucleotide replacement in codon 35 of the human leukocyte antigen HLA
      A*11:01:01 results in a new allele, HLA-A*11:166. 

PMID- 24899341
TI  - Global analysis of muscle-specific kinase signaling by quantitative
      phosphoproteomics.
AB  - The development of the neuromuscular synapse depends on signaling processes that
      involve protein phosphorylation as a crucial regulatory event. Muscle-specific
      kinase (MuSK) is the key signaling molecule at the neuromuscular synapse whose
      activity is required for the formation of a mature and functional synapse.
      However, the signaling cascade downstream of MuSK and the regulation of the
      different components are still poorly understood. In this study we used a
      quantitative phosphoproteomics approach to study the phosphorylation events and
      their temporal regulation downstream of MuSK. We identified a total of 10,183
      phosphopeptides, of which 203 were significantly up- or down-regulated. Regulated
      phosphopeptides were classified into four different clusters according to their
      temporal profiles. Within these clusters we found an overrepresentation of
      specific protein classes associated with different cellular functions. In
      particular, we found an enrichment of regulated phosphoproteins involved in
      posttranscriptional mechanisms and in cytoskeletal organization. These findings
      provide novel insights into the complex signaling network downstream of MuSK and
      form the basis for future mechanistic studies. 

PMID- 24899342
TI  - A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification
      from next-generation sequencing of clinical samples.
AB  - Unbiased next-generation sequencing (NGS) approaches enable comprehensive
      pathogen detection in the clinical microbiology laboratory and have numerous
      applications for public health surveillance, outbreak investigation, and the
      diagnosis of infectious diseases. However, practical deployment of the technology
      is hindered by the bioinformatics challenge of analyzing results accurately and
      in a clinically relevant timeframe. Here we describe SURPI ("sequence-based
      ultrarapid pathogen identification"), a computational pipeline for pathogen
      identification from complex metagenomic NGS data generated from clinical samples,
      and demonstrate use of the pipeline in the analysis of 237 clinical samples
      comprising more than 1.1 billion sequences. Deployable on both cloud-based and
      standalone servers, SURPI leverages two state-of-the-art aligners for accelerated
      analyses, SNAP and RAPSearch, which are as accurate as existing bioinformatics
      tools but orders of magnitude faster in performance. In fast mode, SURPI detects
      viruses and bacteria by scanning data sets of 7-500 million reads in 11 min to 5
      h, while in comprehensive mode, all known microorganisms are identified, followed
      by de novo assembly and protein homology searches for divergent viruses in 50 min
      to 16 h. SURPI has also directly contributed to real-time microbial diagnosis in
      acutely ill patients, underscoring its potential key role in the development of
      unbiased NGS-based clinical assays in infectious diseases that demand rapid
      turnaround times. 

PMID- 24899345
TI  - [What mirror neurons have revealed: revisited].
AB  - The first paper on mirror neurons was published in 1992. In the span of over two
      decades since then, much knowledge about the relationship between social
      cognitive function and the motor control system has been accumulated. Direct
      matching of visual actions and their corresponding motor representations is the
      most important functional property of mirror neuron. Many studies have emphasized
      intrinsic simulation as a core concept for mirror neurons. Mirror neurons are
      thought to play a role in social cognitive function. However, the function of
      mirror neurons in the macaque remains unclear, because such cognitive functions
      are limited or lacking in macaque monkeys. It is therefore important to discuss
      these neurons in the context of motor function. Rizzolatti and colleagues have
      stressed that the most important function of mirror neurons in macaques is
      recognition of actions performed by other individuals. I suggest that mirror
      neurons in the Macaque inferior pariental lobule might be correlated with body
      schema. In the parieto-premotor network, matching of corollary discharge and
      actual sensory feedback is an essential neuronal operation. Recently, neurons
      showing mirror properties were found in some cortical areas outside the mirror
      neuron system. The current work would revisit the outcomes of mirror neuron
      studies to discuss the function of mirror neurons in the monkey.

PMID- 24899344
TI  - Investigating the association between obesity and asthma in 6- to 8-year-old
      Saudi children: a matched case-control study.
AB  - BACKGROUND: Previous studies have demonstrated an association between obesity and
      asthma, but there remains considerable uncertainty about whether this reflects an
      underlying causal relationship. AIMS: To investigate the association between
      obesity and asthma in pre-pubertal children and to investigate the roles of
      airway obstruction and atopy as possible causal mechanisms. METHODS: We conducted
      an age- and sex-matched case-control study of 1,264 6- to 8-year-old
      schoolchildren with and without asthma recruited from 37 randomly selected
      schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference
      and skin fold thickness of the 632 children with asthma were compared with those
      of the 632 control children without asthma. Associations between obesity and
      asthma, adjusted for other potential risk factors, were assessed separately in
      boys and girls using conditional logistic regression analysis. The possible
      mediating roles of atopy and airway obstruction were studied by investigating the
      impact of incorporating data on sensitisation to common aeroallergens and
      measurements of lung function. RESULTS: BMI was associated with asthma in boys
      (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08-1.20; adjusted OR=1.11,
      95% CI, 1.03-1.19) and girls (OR=1.37, 95% CI, 1.26-1.50; adjusted OR=1.38, 95%
      CI, 1.23-1.56). Adjusting for forced expiratory volume in 1 s had a negligible
      impact on these associations, but these were attenuated following adjustment for
      allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96-1.60;
      boys: OR=1.09, 95% CI, 0.99-1.19). CONCLUSIONS: BMI is associated with asthma in
      pre-pubertal Saudi boys and girls; this effect does not appear to be mediated
      through respiratory obstruction, but in girls this may at least partially be
      mediated through increased risk of allergic sensitisation.

PMID- 24899346
TI  - [Human mirror neuron system].
AB  - In this paper, we introduced the temporal and information representation
      properties of the human mirror neuron system (MNS) that have been revealed by
      using noninvasive imaging techniques (magnetic resonance imaging (MRI), positron
      emission tomography (PET), and noninvasive brain stimulation such as transcranial
      magnetic stimulation (TMS) or electrical stimulation). Next, we discussed the
      neural networks involved in action understanding and affordance. In this paper,
      we especially emphasized the role of MNS in prediction and action recognition,
      and introduced recent brain theories and a neural network model, based on several
      MNS properties, including the prediction function, the free energy principle, and
      the minimization of prediction error.

PMID- 24899347
TI  - [The mirror neuron system in motor and sensory rehabilitation].
AB  - The discovery of the mirror neuron system has dramatically changed the study of
      motor control in neuroscience. The mirror neuron system provides a conceptual
      framework covering the aspects of motor as well as sensory functions in motor
      control. Previous studies of motor control can be classified as studies of motor
      or sensory functions, and these two classes of studies appear to have advanced
      independently. In rehabilitation requiring motor learning, such as relearning
      movement after limb paresis, however, sensory information of feedback for motor
      output as well as motor command are essential. During rehabilitation from chronic
      pain, motor exercise is one of the most effective treatments for pain caused by
      dysfunction in the sensory system. In rehabilitation where total intervention
      unifying the motor and sensory aspects of motor control is important, learning
      through imitation, which is associated with the mirror neuron system can be
      effective and suitable. In this paper, we introduce the clinical applications of
      imitated movement in rehabilitation from motor impairment after brain damage and
      phantom limb pain after limb amputation.

PMID- 24899348
TI  - [Mirror neuron system dysfunction in schizophrenia and its clinical implication].
AB  - Since the discovery of mirror neuron system, several neurophysiological and
      neuroimaging studies showed that the mirror neuron system might have a role in
      understanding other people's actions and intentions with automatic simulation of
      their actions. Moreover, some studies suggested that mirror neurons have a
      broader role in social cognition including understanding others' emotions and
      empathy. It has not been proved, however, whether the mirror neuron system is
      necessarily involved in empathy processes. In the domain of social cognition
      deficits, it is important to investigate the involvement of mirror neuron system
      dysfunction in psychosis such as schizophrenia. Using magnetoencephalography, we
      examined whether antipsychotic-free schizophrenia patients displayed mirror
      neuron system dysfunction during observation of biological motion (jaw movement).
      Compared with normal controls, the patients with schizophrenia had fewer
      components of both the waveform and equivalent current dipole, suggesting
      aberrant brain activity resulting from dysfunction of the right inferior parietal
      cortex. They also lacked the changes of alpha band and gamma band oscillation
      seen in normal controls, and had weaker phase locking factors and gamma
      synchronization predominantly in right parietal cortex. This finding demonstrated
      that untreated patients with schizophrenia exhibited aberrant mirror neuron
      system function based on the right inferior parietal cortex, which is
      characterized by dysfunction of gamma-synchronization.

PMID- 24899349
TI  - [The ontogeny of the mirror neuron system].
AB  - Abstract Humans utilize the mirror neuron system to understand and predict
      others' actions. However, the ontogeny of the mirror neuron system remains
      unknown. Whether mirror neuron function is an innate trait or whether mirror
      neurons acquire their sensorimotor matching properties ontogenetically remains to
      be clarified. In this paper, I review the ontogenetic theory of the mirror neuron
      system. I then discuss the functioning of the mirror neuron system in the context
      of social cognitive abilities, which are unique to humans. Recently, some
      researchers argue that it is too early to interpret the function of mirror
      neurons as an understanding of the underlying psychological states of others.
      They imply that such functioning would require inferential cognitive processes
      that are known to involve areas outside the mirror neuron system. Filling in this
      missing link may be the key to elucidating the unique ability of humans to
      understand others' actions. 

PMID- 24899350
TI  - [Multilayered control of the Mammalian circadian system].
AB  - All mammals show daily rhythms in their physiological activity, for example,
      sleep-wake cycles. This rhythmicity is endogenously generated by a system called
      the circadian clock, and is composed of reactions occurring in several
      neural/cellular layers of multicellular organisms. Inter-cellular and inter-organ
      communication is important for the synchronous action of circadian rhythmicity
      across the whole body. The heart of the circadian system lies in the rhythmic
      neuronal activity of the suprachiasmatic nuclei (SCN) in the brain. The
      oscillation emerges as cell-autonomous rhythmic gene expression observed in
      individual SCN neurons. Inter-neuronal communication synchronizes the circadian
      phase of each neuron within the SCN. The integrated rhythmic SCN activity works
      as a pacemaker for the circadian clocks of non-SCN cells, each of which also
      rhythmically express clock genes. The -24-h period length of the circadian rhythm
      is predominantly determined by reactions at the molecular level. Cell-autonomous
      circadian oscillation is driven by a negative feedback loop of transcription
      regulation, where CRY/PER heterodimers act as the transcriptional repressors of
      their own genes. One of the rate limiting steps of circadian cycling is a
      phosphorylation of CRY and PER proteins followed by proteasome-mediated
      degradation of those proteins. Pharmacological and genetic perturbation of the
      phosphorylation or degradation pathways alters the circadian period length. This
      review provides a hierarchical view of the circadian system, which is important
      to uncover the different effects of medical or social perturbations on circadian
      regulation of inter-cellular synchronization, or cell-autonomous oscillation.

PMID- 24899351
TI  - [Alzheimer's Disease Cooperative Study (ADCS)].
AB  - The Alzheimer's Disease Cooperative Study (ADCS) started in 1991 as part of an
      agreement between the National Institute on Aging (NIA) and the University of
      California, San Diego, is a major clinical activity for treating Alzheimer's
      disease (AD). As part of the NIA Division, the ADCS supports all activities for
      AD treatment, including the discovery and evaluation of new diagnostic methods,
      drugs, and devices for patients with AD, as well as the prevention of AD.

PMID- 24899352
TI  - [The utility of voxel-based morphometry in the diagnosis of spinocerebellar
      degeneration].
AB  - We evaluated atrophic sites in the brainstem and cerebellum in the patients with
      spinocerebellar degeneration by using voxel-based morphometry (VBM). Gray matter
      atrophy was found extensively in both the cerebellar hemispheres and vermis of
      subjects presenting the cerebellar variant of multiple system atrophy (MSA-C;
      n=9). In addition, remarkable white matter atrophy was observed in the middle
      cerebellar peduncle, brainstem, and cerebellar hemispheres. In contrast, gray
      matter atrophy was not apparent in the cerebellar hemispheres or vermis of
      subjects in the SCA3 group (n=6), whereas intense white matter atrophy was
      visible in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres.
      White matter atrophy was also observed in the brainstem and surrounding the
      dentate nucleus in both cases of dentatorubral-pallidoluysian atrophy (DRPLA)
      (n=2), whereas gray matter atrophy of the cerebellum was not remarkable. In both
      the SCA6 group (n=3) and the SCA31 group (n=2), gray matter atrophy was prominent
      in the cerebellar hemispheres and vermis; however, white matter atrophy was not
      found in the middle cerebellar peduncle and brainstem, whereas symmetric atrophy
      of white matter was found in the vicinity of the dentate nucleus. In each of
      these diseases, VBM findings were consistent with the pathological findings;
      therefore, VBM can be considered a useful tool for the diagnosis of
      spinocerebellar degeneration.

PMID- 24899353
TI  - [A case of a venous angioma with CT findings similar to those of striatocapsular
      infarction].

PMID- 24899354
TI  - Spectrum of renal disease in diabetes.
AB  - The spectrum of renal disease in patients with diabetes encompasses both diabetic
      kidney disease (including albuminuric and non-albuminuric phenotypes) and non
      diabetic kidney disease. Diabetic kidney disease can manifest as varying degrees
      of renal insufficiency and albuminuria, with heterogeneity in histology reported
      on renal biopsy. For patients with diabetes and proteinuria, the finding of non
      diabetic kidney disease alone or superimposed on the changes of diabetic
      nephropathy is increasingly reported. It is important to identify non-diabetic
      kidney disease as some forms are treatable, sometimes leading to remission.
      Clinical indications for a heightened suspicion of non-diabetic kidney disease
      and hence consideration for renal biopsy in patients with diabetes and
      nephropathy include absence of diabetic retinopathy, short duration of diabetes,
      atypical chronology, presence of haematuria or other systemic disease, and the
      nephrotic syndrome. 

PMID- 24899355
TI  - Do patients with advanced cancer value the physical examination?

PMID- 24899357
TI  - Clot properties and cardiovascular disease.
AB  - Fibrinogen is cleaved by thrombin to fibrin, which provides the blood clot with
      its essential structural backbone. As an acute phase protein, the plasma levels
      of fibrinogen are increased in response to inflammatory conditions. In addition
      to fibrinogen levels, fibrin clot structure is altered by a number of factors.
      These include thrombin levels, treatment with common cardiovascular medications,
      such as aspirin, anticoagulants, statins and fibrates, as well as metabolic
      disease states such as diabetes mellitus and hyperhomocysteinaemia. In vitro
      studies of fibrin clot structure can provide information regarding fibre density,
      clot porosity, the mechanical strength of fibres and fibrinolysis. A change in
      fibrin clot structure, to a denser clot with smaller pores which is more
      resistant to lysis, is strongly associated with cardiovascular disease. This
      pathological change is present in patients with arterial as well as venous
      diseases, and is also found in a moderate form in relatives of patients with
      cardiovascular disease. Pharmacological therapies, aimed at both the treatment
      and prophylaxis of cardiovascular disease, appear to result in positive changes
      to the fibrin clot structure. As such, therapies aimed at 'normalising' fibrin
      clot structure may be of benefit in the prevention and treatment of
      cardiovascular disease. 

PMID- 24899356
TI  - The Structured Clinical Interview for DSM-IV Childhood Diagnoses (Kid-SCID):
      first psychometric evaluation in a Dutch sample of clinically referred youths.
AB  - The Structured Clinical Interview for DSM-IV Childhood Disorders (Kid-SCID) is a
      semi-structured interview for the classification of psychiatric disorders in
      children and adolescents. This study presents a first evaluation of the
      psychometric properties of the Kid-SCID in a Dutch sample of children and
      adolescents who had been referred to an outpatient treatment centre for mental
      health problems. Results indicated that the inter-rater reliability of the Kid
      SCID classifications and the internal consistency of various (dimensional)
      criteria of the diagnoses were moderate to good. Further, for most Kid-SCID
      diagnoses, reasonable agreement between children and parents was found. Finally,
      the correspondence between the Kid-SCID and the final clinical diagnosis as
      established after the full intake procedure, which included the information as
      provided by the Kid-SCID, ranged from poor to good. Results are discussed in the
      light of methodological issues pertaining to the assessment of psychiatric
      disorders in youths. The Kid-SCID can generally be seen as a reliable and useful
      tool that can assist clinicians in carrying out clinical evaluations of children
      and adolescents. 

PMID- 24899359
TI  - Childhood loss of control eating over five-year follow-up.
AB  - OBJECTIVE: Emerging prospective evidence from mixed samples, mostly covering
      short-term follow-up periods, suggests that childhood loss of control (LOC)
      eating predicts significant impairment in mental and physical health. This study
      sought to investigate the natural course of childhood LOC eating over the long
      term and in relation to binge-eating disorder (BED) diagnosis, psychopathology,
      and body weight trajectory in the community. METHOD: A total of 60 children (8-13
      years) with LOC eating within the past 3 months and 60 demographically matched
      children without LOC history were assessed with the Eating Disorder Examination
      adapted for Children and self-report questionnaires over a 5.5 year follow-up
      period. Missing data were imputed. RESULTS: Over follow-up, 38.3% of children
      showed persistent LOC eating, and 28.3% revealed an onset of LOC eating.
      Persistent LOC eating significantly predicted onset of partial-/full-syndrome BED
      at follow-up. Negative prognostic effects on eating disorder psychopathology,
      depressive symptoms, and body mass index were nonsignificant. DISCUSSION: The
      results indicate a moderate stability of LOC eating over the long term. LOC
      eating, especially if stable, was suggested as a variable risk factor of
      clinically relevant eating disturbances. In contrast, a prognostic value for
      psychopathology and body mass index was not confirmed.

PMID- 24899358
TI  - Design, synthesis, conformational analysis and application of indolizidin-2-one
      dipeptide mimics.
AB  - Growth in the field of peptide mimicry over the past few decades has resulted in
      the synthesis of many new compounds and the investigation of novel
      pharmacological agents. Azabicyclo[X.Y.0]alkanone amino acids are among the
      attractive classes of constrained mimics, because they can create rigid peptide
      structures for probing the conformation and roles of natural motifs in
      recognition events important for biological activity. Herein, we review the last
      ten years of the synthesis, conformational analysis and activity of analogs of
      the azabicyclo[4.3.0]alkan-2-one amino acid subclass, so-called indolizidin-2-one
      amino acids, with particular attention on their employment as inputs for
      biological applications. 

PMID- 24899361
TI  - Elastic and wearable wire-shaped lithium-ion battery with high electrochemical
      performance.
AB  - A stretchable wire-shaped lithium-ion battery is produced from two aligned multi
      walled carbon nanotube/lithium oxide composite yarns as the anode and cathode
      without extra current collectors and binders. The two composite yarns can be well
      paired to obtain a safe battery with superior electrochemical properties, such as
      energy densities of 27 Wh kg(-1) or 17.7 mWh cm(-3) and power densities of 880 W
      kg(-1) or 0.56 W cm(-3), which are an order of magnitude higher than the
      densities reported for lithium thin-film batteries. These wire-shaped batteries
      are flexible and light, and 97 % of their capacity was maintained after 1000
      bending cycles. They are also very elastic as they are based on a modified spring
      structure, and 84 % of the capacity was maintained after stretching for 200
      cycles at a strain of 100 %. Furthermore, these novel wire-shaped batteries have
      been woven into lightweight, flexible, and stretchable battery textiles, which
      reveals possible large-scale applications.

PMID- 24899360
TI  - A rapid, simple questionnaire to assess gastrointestinal symptoms after oral
      ferrous sulphate supplementation.
AB  - BACKGROUND: Oral iron supplementation is often associated with rapid onset of
      gastrointestinal side-effects. The aim of this study was to develop and trial a
      short, simple questionnaire to capture these early side-effects and to determine
      which symptoms are more discriminating. METHODS: The study was a double-blind
      placebo-controlled randomized parallel trial with one week treatment followed by
      one week wash-out. Subjects were randomized into two treatment groups (n =
      10/group) to receive either ferrous sulphate (200 mg capsules containing 65 mg of
      iron) or placebo, both to be taken at mealtimes twice daily during the treatment
      period. Subjects completed the questionnaires daily for 14 days. The
      questionnaire included gastrointestinal symptoms commonly reported to be
      associated with the oral intake of ferrous iron salts (i.e. nausea, vomiting,
      heartburn, abdominal pain, diarrhoea, and constipation). RESULTS: Seventy five
      per cent of participants reporting the presence of one or more symptoms in the
      first week of the study were in the ferrous sulphate group. In the second week of
      the study (i.e. wash-out), 67% of the participants reporting one or more
      symptom(s) were in the ferrous sulphate group. In the first week of the study
      (treatment) the number of symptoms reported by participants in the ferrous
      sulphate group (mean +/- SEM = 6.7 +/- 1.7) was significantly higher than that
      for participants in the placebo group (1.2 +/- 0.5) (p = 0.01). In the second
      week of the study (wash-out) the number of symptoms reported by participants in
      the ferrous sulphate group (4.6 +/- 2.0) appeared higher than for participants in
      the placebo group (1.0 +/- 0.7) although this did not reach significance (p =
      0.12). Events for which the gastrointestinal symptom questionnaire was most
      discriminatory between ferrous sulphate and placebo groups were: heartburn,
      abdominal pain and the presence of black stools (all p <= 0.03). CONCLUSIONS: A
      tool for the detection of commonly-occurring side effects should not require
      large study numbers to be effective. With just 10 subjects per group (iron or
      placebo), this simple questionnaire measures gastrointestinal side-effects
      associated with oral iron (ferrous sulphate) supplementation, and would be
      appropriate for use in intervention studies or clinical trials. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT02146053 (21/05/2014).

PMID- 24899363
TI  - Alkaloids from the hook-bearing branch of Uncariarhynchophylla and their
      neuroprotective effects against glutamate-induced HT22 cell death.
AB  - One new alkaloid, 4-geissoschizine N-oxide methyl ether (1), was isolated from
      the EtOH extract of the hook-bearing branch of Uncariarhynchophylla, together
      with 10 known alkaloids, 3-epi-geissoschizine methyl ether (2) isolated from
      U.rhynchophylla for the first time, geissoschizine methyl ether (3), 4-hirsuteine
      N-oxide (4), hirsuteine (5), hirsutine (6), 3alpha-dihydro-cadambine (7), 3beta
      isodihydro-cadambine (8), cadambine (9), strictosamide (10), and akuammigine
      (11). The structures were elucidated by spectroscopic methods including UV, ESI
      QTOF MS, NMR, and circular dichroism experiments. Neuroprotective effects of 1-9
      were investigated against 3 mM glutamate-induced HT22 cell death. The activity
      assay showed that 2, 3, 5, and 6 exhibited potent neuroprotective effects against
      glutamate-induced HT22 cell death. However, only weak neuroprotective activities
      were observed for 1, 4, 7, 8, and 9. 

PMID- 24899362
TI  - Site-specific labeling of proteins and peptides with trans-cyclooctene containing
      handles capable of tetrazine ligation.
AB  - There is a growing library of functionalized non-natural substrates for the
      enzyme protein farnesyltransferase (PFTase). PFTase covalently attaches these
      functionalized non-natural substrates to proteins ending in the sequence CAAX,
      where C is a cysteine that becomes alkylated, A represents an aliphatic amino
      acid, and X is Ser, Met, Ala, or Gln. Reported substrates include a variety of
      functionalities that allow modified proteins to undergo subsequent bioconjugation
      reactions. To date the most common strategy used in this approach has been copper
      catalyzed azide-alkyne cycloaddition (CuAAC). While being fast and bioorthogonal
      CuAAC has limited use in live cell experiments due to copper's toxicity.(1) Here,
      we report the synthesis of trans-cyclooctene geranyl diphosphate. This substrate
      can be synthesized from geraniol in six steps and be enzymatically transferred to
      peptides and proteins that end in a CAAX sequence. Proteins and peptides site
      specially modified with trans-cyclooctene geranyl diphosphate were subsequently
      targeted for further modification via tetrazine ligation. As tetrazine ligation
      is bioorthogonal, fast, and is contingent on ring strain rather than the addition
      of a copper catalyst, this labeling strategy should prove useful for labeling
      proteins where the presence of copper may hinder solubility or biological
      reactivity. 

PMID- 24899364
TI  - A cascade amplification strategy based on rolling circle amplification and
      hydroxylamine amplified gold nanoparticles enables chemiluminescence detection of
      adenosine triphosphate.
AB  - A highly sensitive and selective chemiluminescent (CL) biosensor for adenosine
      triphosphate (ATP) was developed by taking advantage of the ATP-dependent
      enzymatic reaction (ATP-DER), the powerful signal amplification capability of
      rolling circle amplification (RCA), and hydroxylamine-amplified gold
      nanoparticles (Au NPs). The strategy relies on the ability of ATP, a cofactor of
      T4 DNA ligase, to trigger the ligation-RCA reaction. In the presence of ATP, the
      T4 DNA ligase catalyzes the ligation reaction between the two ends of the padlock
      probe, producing a closed circular DNA template that initiates the RCA reaction
      with phi29 DNA polymerase and dNTP. Therein, many complementary copies of the
      circular template can be generated. The ATP-DER is eventually converted into a
      detectable CL signal after a series of processes, including gold probe
      hybridization, hydroxylamine amplification, and oxidative gold metal dissolution
      coupled with a simple and sensitive luminol CL reaction. The CL signal is
      directly proportional to the ATP level. The results showed that the detection
      limit of the assay is 100 pM of ATP, which compares favorably with those of other
      ATP detection techniques. In addition, by taking advantage of ATP-DER, the
      proposed CL sensing system exhibits extraordinary specificity towards ATP and
      could distinguish the target molecule ATP from its analogues. The proposed method
      provides a new and versatile platform for the design of novel DNA ligation
      reaction-based CL sensing systems for other cofactors. This novel ATP-DER based
      CL sensing system may find wide applications in clinical diagnosis as well as in
      environmental and biomedical fields. 

PMID- 24899365
TI  - A molecular signaling approach to linking intraspecific variation and macro
      evolutionary patterns.
AB  - Macro-evolutionary comparisons are a valued tool in evolutionary biology.
      Nevertheless, our understanding of how systems involved in molecular signaling
      change in concert with phenotypic diversification has lagged. We argue that
      integrating our understanding of the evolution of molecular signaling systems
      with phylogenetic comparative methods is an important step toward understanding
      the processes linking variation among individuals with variation among species.
      Focusing mostly on the endocrine system, we discuss how the complexity and
      mechanistic nature of molecular signaling systems may influence the application
      and interpretation of macro-evolutionary comparisons. We also detail five
      hypotheses concerning the role that physiological mechanisms can play in shaping
      macro-evolutionary patterns, and discuss ways in which these hypotheses could
      influence phenotypic diversification. Finally, we review a series of tools able
      to analyze the complexity of physiological systems and the way they change in
      concert with the phenotypes for which they coordinate development. 

PMID- 24899367
TI  - Evidence-based review of photodynamic therapy in the treatment of acne.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been used for acne, however, the
      efficacy and safety need to be determined. OBJECTIVE: To assess the effects and
      safety of PDT for acne using an evidence-based approach. METHODS: Randomized
      controlled trials (RCTs) on the treatment of acne with PDT were identified by
      searching PubMed, CNKI and the Cochrane Library. RESULTS: A total of 14 RCTs
      involving 492 patients were included. Photosensitizers included aminolevulinic
      acid (ALA), methylaminolevulinate (MAL), and indole-3-acetic acid (IAA). Light
      sources included red light, pulsed dye laser (PDL), intense pulsed light (IPL),
      long-pulsed dye laser (LPDL) and green light. The PDT protocols, including ALA +
      red light, ALA + PDL, ALA + IPL, MAL + red light, and MAL + LPDL, all showed
      great efficacy on inflammatory lesions. ALA + red light also had effects on non
      inflammatory lesions and sebum secretion. ALA + IPL and IAA + green light
      significantly decreased sebum secretion. Triple treatment protocols showed great
      improvement on inflammatory and non-inflammatory lesions. Increasing ALA
      concentration, ALA incubation time, PDT sessions, dose of light source or using
      occlusion for photosensitizers, or a combination of other treatments with PDT may
      achieve greater efficacy. The common side effects of PDT were tolerable and
      transient. CONCLUSION: Limited evidence indicates that PDT shows good efficacy in
      the treatment of acne with acceptable side effects. ALA + red light was shown to
      be the optimal choice. However, more RCTs are needed to determine the types and
      concentrations of photosensitizers and light sources, and the duration of light
      activation and incubation.

PMID- 24899368
TI  - Vertebrate neurogenic placode development: historical highlights that have shaped
      our current understanding.
AB  - With the flood of published research encountered today, it is important to
      occasionally reflect upon how we arrived at our current understanding in a
      particular scientific discipline, thereby positioning new discoveries into proper
      context with long-established models. This historical review highlights some of
      the important scientific contributions in the field of neurogenic placode
      development. By viewing cumulatively the rich historical data, we can more fully
      appreciate and apply what has been accomplished. Early descriptive work in fish
      and experimental approaches in amphibians and chick yielded important conceptual
      models of placode induction and cellular differentiation. Current efforts to
      discover genes and their molecular functions continue to expand our understanding
      of the placodes. Carefully considering the body of work may improve current
      models and help focus modern experimental design.

PMID- 24899369
TI  - Clinical Sentinel Surveillance of Equine West Nile Fever, Spain.
AB  - West Nile fever (WNF) is a viral zoonotic infection caused by a mosquito-borne
      flavivirus of the Flaviviridae family. According to a comparative study, the
      passive surveillance of horses by equine veterinarians appeared to be the most
      cost-effective system in the European context of WNF. Clinical data issued from a
      passive epidemiosurveillance network from September 2010 to December 2011 on
      horses in Spain were statistically compared and used to develop a predictive
      diagnostic decision tree, both with the aim to improve the early clinical
      detection of WNF in horses. Although clinical signs were variable in horses
      affected by WNF, four clinical signs and the month of occurrence were identified
      as useful indicators to distinguish between WNF-related and WNF-unrelated cases.
      The signs that pointed out a presumptive diagnosis of WNF in horses were cranial
      nerves deficits, limb paralysis, photophobia and nasal discharge. Clinical
      examination of horses with neurological signs that are not vaccinated against WNV
      could provide important clues for the early clinical detection of WNF and
      therefore serve as an alert for possible human viral infections. The study of the
      clinical pattern of WNF in horses is of importance to enhance awareness and
      better understanding and to optimize surveillance designs for clinical detection
      of WNF in horses in advance of epidemic activity affecting humans. 

PMID- 24899370
TI  - Unlocking the quiet zone: the small airway asthma phenotype.
AB  - The small airways in the distal lung have been called the quiet zone because they
      are difficult to assess and treat in patients with asthma who have
      disproportionate impairment of small airway function. Evidence is accumulating to
      support a distinct clinical phenotype for patients with asthma who have impaired
      small airway function. The small airway asthma phenotype, which is prevalent in
      patients at all steps of management guidelines, seems to be associated with poor
      disease control. Alternatively, small airway dysfunction might be a sensitive
      indicator of early disease rather than a phenotype. Conventional coarse-particle
      inhalers, which emit particles larger than 2 MUm, might not address persistent
      small airway dysfunction in patients with asthma. To target the entire lung with
      extra-fine particle formulations (smaller than 2 MUm) of inhaled corticosteroids
      alone or in combination with long-acting beta-agonists might result in improved
      long-term asthma control along with a commensurate improvement in small airway
      function. Prospective randomised controlled trials with extra-fine-particle
      inhaled drugs are now needed for patients with the small airway asthma phenotype.

PMID- 24899371
TI  - Further evidence for the effectiveness of PCV10 against Streptococcus pneumoniae
      serotype 19A.

PMID- 24899372
TI  - Development and psychometric evaluation of scales to measure professional
      confidence in manual medicine: a Rasch measurement approach.
AB  - BACKGROUND: Health professionals in athletic training, chiropractic, osteopathy,
      and physiotherapy fields, require high-level knowledge and skills in their
      assessment and management of patients. This is important when communicating with
      patients and applying a range of manual procedures. Prior to embarking on
      professional practice, it is imperative to acquire optimal situation-specific
      levels of self-confidence for a beginner practitioner in these areas. In order to
      foster this professional self-confidence within the higher education context, it
      is necessary to have valid and reliable scales that can measure and track levels
      and how they change. This study reports on the development and psychometric
      analysis of two new scales, Patient Communication Confidence Scale (PCCS) and the
      Clinical Skills Confidence Scale (CSCS), to measure confidence in these two areas
      for students in manual medicine programs. The Rasch measurement model was used to
      guide the development of the scales and establish their psychometric properties.
      METHODS: The responses to 269 returned questionnaires over two occasions were
      submitted to psychometric analysis, with various aspects of the scales examined
      including: item thresholds; item fit; Differential Item Functioning; targeting;
      item locations; item dependencies; and reliability. To provide further evidence
      of validity, scores were correlated with two existing valid scales. RESULTS:
      Analyses showed that the scales provided valid and reliable measures of
      confidence for this sample of persons. High Person Separation Indices (0.96 for
      PCCS; 0.93 for SCSC) provided statistical evidence of reliability, meaning the
      scales are able to discriminate amongst persons with different levels of
      confidence. For the PCCS, item categories were operating as required, and for the
      CSCS only two items' thresholds were slightly disordered. Three tests of fit
      revealed good fit to the model (indicating the internal consistency of both
      scales) and results of the correlations with two existing valid scales were
      consistent with expectations. CONCLUSIONS: The importance of confidence cannot be
      overlooked in health education because students learning new information and
      skills, and dealing with challenging situations can be negatively impacted by a
      lack of confidence which can result in students disengaging from placements or
      leaving a program. Valid and reliable instruments are essential in tracking
      change in levels of confidence in specific skills over time and the examination
      of the degree of congruence between confidence and competence. Analysis of
      responses to the two confidence scales established that they are valid and
      reliable instruments.

PMID- 24899373
TI  - Intravascular molecular imaging for atherosclerosis: a fledgling but realistic
      world with lights and ultrasounds.

PMID- 24899374
TI  - Stem cells bond our organs/tissues and engineering products.

PMID- 24899375
TI  - How should we apply the CHA2DS2-VASc score to non-valvular atrial fibrillation
      patients in Japan?

PMID- 24899376
TI  - Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate
      derivatives.
AB  - The present study reported the synthesis of tetrahydrocarbazoles hybridized with
      dithioate derivatives. Three series were synthesized namely alkyl
      dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl
      dithiocarbamate (7). The synthesized compounds were tested in vitro on human
      breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line
      (HCT116). Most of the synthesized compounds exploited potent antitumor activity,
      especially compound 6f [4-chlorophenylpiperazine derivative], which showed
      cytotoxic activity against MCF7 superior to doxorubicin with IC50 value of 7.24
      nM/mL. 

PMID- 24899377
TI  - Inhibition of human pyridoxal kinase by 2-acetyl-4-((1R,2S,3R)-1,2,3,4
      tetrahydroxybutyl)imidazole (THI).
AB  - 2-Acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI) is observed as a
      minor contaminant in caramel food colourings (E 150c). Feeding experiments with
      rodents have revealed a significant lymphopenic effect that has been linked to
      the presence of THI in these food colourings. Pyridoxal kinase inhibition by THI
      has been suggested, but not demonstrated, as a mode of action as it leads to
      lowered levels of pyridoxal-5'-phosphate, which are known to cause lymphopenia.
      Recently, THI was also shown to inhibit sphingosine-1-phosphate lyase causing
      comparable immunosuppressive effects and derivatives of THI are being developed
      for the treatment of rheumatoid arthritis in humans. Interestingly, sphingosine-1
      phosphate lyase activity depends on pyridoxal-5'-phosphate, which in turn is
      provided by pyridoxal kinase. This report shows that THI does inhibit pyridoxal
      kinase with competitive and mixed-type non-competitive behaviour towards its two
      substrates, pyridoxal and ATP, respectively. The corresponding inhibition
      constants are in the low millimolar range. 

PMID- 24899379
TI  - Effects of noise reduction on AM perception for hearing-impaired listeners.
AB  - Noise reduction (NR) systems are commonplace in modern digital hearing aids.
      Though not improving speech intelligibility, NR helps the hearing-aid user in
      terms of lowering noise annoyance, reducing cognitive load and improving ease of
      listening. Previous psychophysical work has shown that NR does in fact improve
      the ability of normal-hearing (NH) listeners to discriminate the slow amplitude
      modulation (AM) cues representative of those found in speech. The goal of this
      study was to assess whether this improvement of AM discrimination with NR can
      also be observed for hearing-impaired (HI) listeners. AM discrimination was
      measured at two audio frequencies of 500 Hz and 2 kHz in a background noise with
      a signal-to-noise ratio of 12 dB. Discrimination was measured for ten HI and ten
      NH listeners with and without NR processing. The HI listeners had a moderate
      sensorineural hearing loss of about 50 dB HL at 2 kHz and normal hearing (<= 20
      dB HL) at 500 Hz. The results showed that most of the HI listeners tended to
      benefit from NR at 500 Hz but not at 2 kHz. However, statistical analyses showed
      that HI listeners did not benefit significantly from NR at any frequency region.
      In comparison, the NH listeners showed a significant benefit from NR at both
      frequencies. For each condition, the fidelity of AM transmission was quantified
      by a computational model of early auditory processing. The parameters of the
      model were adjusted separately for the two groups (NH and HI) of listeners. The
      AM discrimination performance of the HI group (with and without NR) was best
      captured by a model simulating the loss of the fast-acting amplitude compression
      applied by the normal cochlea. This suggests that the lack of benefit from NR for
      HI listeners results from loudness recruitment.

PMID- 24899378
TI  - Cigarette smoking, passive smoking, alcohol consumption, and hearing loss.
AB  - The objective of this large population-based cross-sectional study was to
      evaluate the association between smoking, passive smoking, alcohol consumption,
      and hearing loss. The study sample was a subset of the UK Biobank Resource,
      164,770 adults aged between 40 and 69 years who completed a speech-in-noise
      hearing test (the Digit Triplet Test). Hearing loss was defined as speech
      recognition in noise in the better ear poorer than 2 standard deviations below
      the mean with reference to young normally hearing listeners. In multiple logistic
      regression controlling for potential confounders, current smokers were more
      likely to have a hearing loss than non-smokers (odds ratio (OR) 1.15, 95 %
      confidence interval (CI) 1.09-1.21). Among non-smokers, those who reported
      passive exposure to tobacco smoke were more likely to have a hearing loss (OR
      1.28, 95 %CI 1.21-1.35). For both smoking and passive smoking, there was evidence
      of a dose-response effect. Those who consume alcohol were less likely to have a
      hearing loss than lifetime teetotalers. The association was similar across three
      levels of consumption by volume of alcohol (lightest 25 %, OR 0.61, 95 %CI 0.57
      0.65; middle 50 % OR 0.62, 95 %CI 0.58-0.66; heaviest 25 % OR 0.65, 95 %CI 0.61
      0.70). The results suggest that lifestyle factors may moderate the risk of
      hearing loss. Alcohol consumption was associated with a protective effect.
      Quitting or reducing smoking and avoiding passive exposure to tobacco smoke may
      also help prevent or moderate age-related hearing loss. 

PMID- 24899381
TI  - The top clinical trial opportunities in therapeutic apheresis and neurology.
AB  - OBJECTIVE: The National Heart, Lung, and Blood Institute, of The National
      Institutes of Health, convened the 2012 State-of-the-Science Symposium in
      therapeutic apheresis (TA) with the goals of identifying and prioritizing future
      research concept proposals to optimize the use of TA over the next decade.
      METHODS: Six subcommittees, including neurology, were formed based on organ
      system, pathophysiology, and technology/special considerations. The subcommittees
      consisted of physicians, clinical subject matter experts, and basic scientists.
      Each subcommittee developed concept proposals that were presented, evaluated, and
      prioritized based on scientific importance, clinical significance, and
      feasibility. RESULTS: The neurology subcommittee developed eight concept
      proposals. The proposals include therapeutic plasma exchange (TPE) in
      neuromyelitis optica; TPE versus intravenous immunoglobulin (IVIG) in anti-muscle
      specific kinase associated myasthenia gravis, severe acute disseminated
      encephalomyelitis, and anti-NMDA encephalitis; extracorporeal photopheresis in
      relapsing remitting multiple sclerosis and polymyositis; fibrinogen/low-density
      lipoprotein apheresis in idiopathic sudden sensorineural hearing loss; and
      creation of a rare neurologic disease registry and biorepository. CONCLUSIONS:
      Key clinical research priorities to evaluate and optimize the use of TA on
      selected neurologic disorders exist. The research opportunities if addressed
      would provide evidence-based data to inform the care of patients with these
      selected neurologic diseases.

PMID- 24899380
TI  - Detection of modulated tones in modulated noise by non-human primates.
AB  - In natural environments, many sounds are amplitude-modulated. Amplitude
      modulation is thought to be a signal that aids auditory object formation. A
      previous study of the detection of signals in noise found that when tones or
      noise were amplitude-modulated, the noise was a less effective masker, and
      detection thresholds for tones in noise were lowered. These results suggest that
      the detection of modulated signals in modulated noise would be enhanced. This
      paper describes the results of experiments investigating how detection is
      modified when both signal and noise were amplitude-modulated. Two monkeys (Macaca
      mulatta) were trained to detect amplitude-modulated tones in continuous,
      amplitude-modulated broadband noise. When the phase difference of otherwise
      similarly amplitude-modulated tones and noise were varied, detection thresholds
      were highest when the modulations were in phase and lowest when the modulations
      were anti-phase. When the depth of the modulation of tones or noise was varied,
      detection thresholds decreased if the modulations were anti-phase. When the
      modulations were in phase, increasing the depth of tone modulation caused an
      increase in tone detection thresholds, but increasing depth of noise modulations
      did not affect tone detection thresholds. Changing the modulation frequency of
      tone or noise caused changes in threshold that saturated at modulation
      frequencies higher than 20 Hz; thresholds decreased when the tone and noise
      modulations were in phase and decreased when they were anti-phase. The
      relationship between reaction times and tone level were not modified by
      manipulations to the nature of temporal variations in the signal or noise. The
      changes in behavioral threshold were consistent with a model where the brain
      subtracted noise from signal. These results suggest that the parameters of the
      modulation of signals and maskers heavily influence detection in very predictable
      ways. These results are consistent with some results in humans and avians and
      form the baseline for neurophysiological studies of mechanisms of detection in
      noise.

PMID- 24899382
TI  - High-density soft-matter electronics with micron-scale line width.
AB  - A method to produce soft and stretchable microelectronics composed of a liquid
      phase Gallium-Indium alloy with micron-scale circuit features is introduced.
      Microchannels are molded onto the surface of a poly(dimethylsiloxane) (PDMS)
      elastomer and filled with EGaIn using a micro-transfer deposition step that
      exploits the unique wetting properties of EGaIn in air. The liquid-filled
      channels function as stretchable circuit wires or capacitor electrodes with a 2
      MUm linewidth and 1 MUm spacing. 

PMID- 24899383
TI  - Association of placenta organotin concentrations with growth and ponderal index
      in 110 newborn boys from Finland during the first 18 months of life: a cohort
      study.
AB  - BACKGROUND: Humans are exposed to tributyltin (TBT), previously used as an
      antifouling paint in ships, mainly through fish consumption. As TBT is a known
      obesogen, we studied the association of placenta TBT and other organotin
      compounds (OTCs) with ponderal index (PI) and growth during the first 18 months
      of life in boys. METHODS: In a prospective Finnish study, 110 placenta samples
      were collected from mothers of boys born in 1997-1999 with (n = 55) and without
      (n = 55) cryptorchidism. To account for the original study design, linear
      regression, weighted for sampling fractions of boys with (121/55) and without
      (5677/55) cryptorchidism from the total cohort, was used to study the association
      between placenta OTCs and children's weight, length, growth rates and PI up to 18
      months of age. RESULTS: Placenta TBT concentrations were above the limit of
      quantification (LOQ) in 99% of the samples. However, monobutyltin (MBT),
      dibutyltin (DBT) and triphenyltin (TPhT) concentrations were below LOQ in 90%,
      35% and 57% of samples, respectively. Placenta TBT was positively associated (p =
      0.024) with weight gain during the first three months of life, but no other
      significant associations were observed for weight or length gain. Also, no
      significant associations between placenta OTC concentrations and child length,
      weight or PI at any time point were found. CONCLUSIONS: We observed a trend
      towards higher weight gain from birth to 3 months of age with increasing placenta
      TBT concentration. These results should be interpreted with caution because
      obesogenic effects in animal experiments were seen after in-utero TBT exposures
      to doses that were orders of magnitude higher. Also the number of study subjects
      included in this study was limited.

PMID- 24899386
TI  - Remarkable selective constraints on exonic dinucleotide repeats.
AB  - Long dinucleotide repeats found in exons present a substantial mutational hazard:
      mutations at these loci occur often and generate frameshifts. Here, we provide
      clear and compelling evidence that exonic dinucleotides experience strong
      selective constraint. In humans, only 18 exonic dinucleotides have repeat lengths
      greater than six, which contrasts sharply with the genome-wide distribution of
      dinucleotides. We genotyped each of these dinucleotides in 200 humans from eight
      1000 Genomes Project populations and found a near-absence of polymorphism. More
      remarkably, divergence data demonstrate that repeat lengths have been conserved
      across the primate phylogeny in spite of what is likely considerable mutational
      pressure. Coalescent simulations show that even a very low mutation rate at these
      loci fails to explain the anomalous patterns of polymorphism and divergence. Our
      data support two related selective constraints on the evolution of exonic
      dinucleotides: a short-term intolerance for any change to repeat length and a
      long-term prevention of increases to repeat length. In general, our results
      implicate purifying selection as the force that eliminates new, deleterious
      mutants at exonic dinucleotides. We briefly discuss the evolution of the longest
      exonic dinucleotide in the human genome--a 10 x CA repeat in fibroblast growth
      factor receptor-like 1 (FGFRL1)--that should possess a considerably greater
      mutation rate than any other exonic dinucleotide and therefore generate a large
      number of deleterious variants.

PMID- 24899384
TI  - Oral administration of quercetin is unable to protect against isoproterenol
      cardiotoxicity.
AB  - Catecholamines are endogenous amines that participate in the maintenance of
      cardiovascular system homeostasis. However, excessive release or exogenous
      administration of catecholamines is cardiotoxic. The synthetic catecholamine,
      isoprenaline (isoproterenol, ISO), with non-selective beta-agonistic activity has
      been used as a viable model of acute myocardial toxicity for many years. Since
      the pathophysiology of ISO-cardiotoxicity is complex, the aim of this study was
      to elucidate the effect of oral quercetin pretreatment on myocardial ISO
      toxicity. Wistar-Han rats were randomly divided into four groups: solvent or
      quercetin administered orally by gavage in a dose of 10 mg kg(-1) daily for 7
      days were followed by s.c. water for injection or ISO in a dose of 100 mg kg(-1).
      Haemodynamic, ECG and biochemical parameters were measured; effects on blood
      vessels and myocardial histology were assessed, and accompanying pharmacokinetic
      analysis was performed. Quercetin was unable to protect the cardiovascular system
      against acute ISO cardiotoxicity (stroke volume decrease, cardiac troponin T
      release, QRS-T junction elevation and histological impairment). The sole positive
      effect of quercetin on catecholamine-induced cardiotoxicity was the normalization
      of increased left ventricular end-diastolic pressure caused by ISO. Quercetin did
      not reverse the increased responsiveness of rat aorta to vasoconstriction in ISO
      treated animals, but it decreased the same parameter in the control animals.
      Accompanying pharmacokinetic analysis showed absorption of quercetin and its
      metabolite 3-hydroxyphenylacetic acid formed by bacterial microflora. In
      conclusion, a daily oral dose of 10 mg kg(-1) of quercetin for 7 days did not
      ameliorate acute ISO-cardiovascular toxicity in rats despite minor positive
      cardiovascular effects. 

PMID- 24899385
TI  - Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms
      in rats.
AB  - Long-term exposure to opiates induces tolerance to the analgesic effect and
      dependence. The purpose of the present study is to investigate the effects of
      pioglitazone, a peroxisome proliferator-activated receptors gamma (PPAR-gamma)
      agonist, on the morphine-induced tolerance and dependence. Groups of rats
      received morphine in combination with a vehicle or pioglitazone (5, 10, 20, and
      40 mg/kg) daily. Thirty minutes before pioglitazone (40 mg/kg), GW-9662, a
      selective PPAR-gamma antagonist, (2 mg/kg) was administrated in order to evaluate
      the possible role of the PPAR-gamma. Nociception was assessed by a tail flick
      apparatus, and the percentage of the maximal possible effect was calculated as
      well. For 9 days, rats received additive doses of morphine to induce dependence.
      Naloxone was administrated 2 h after the morphine last dose, and withdrawal
      symptoms were recorded for 45 min. Morphine administration to rats over a
      duration of 17 days resulted in the development of tolerance, whereas
      pioglitazone (40 mg/kg) delayed the day of the established tolerance for 15 days.
      Administration of pioglitazone also prevented morphine-induced 50 % effective
      dose (ED50) shift to the right in the dose-response curve and increased the
      global analgesic effect of morphine. In addition, pioglitazone decreased the
      total withdrawal score significantly, whereas GW-9662 significantly reversed the
      pioglitazone effects on the morphine tolerance and dependence. The prevention of
      the morphine-induced glia activation and the proinflammatory responses were the
      possible mechanisms for pioglitazone effect on delaying the morphine tolerance
      and attenuating the dependence. 

PMID- 24899387
TI  - Is there sufficient enhancement of the reduction in CVD rates after a decade of
      statin therapy to justify continuation?
AB  - Randomized, controlled clinical trials have shown significant benefits of statin
      therapy in patients with or at risk for atherosclerotic cardiovascular disease
      (ASCVD). But these trials typically enroll patients for only 5 years or so,
      prompting some clinicians to ask what the longer term follow-up of these patients
      will show. While most trials have a duration of only approximately 5 years, four
      large trials report extended post-trial follow-up to 10 years, and these trials,
      as well as multiple large cohort studies, suggest an expected benefit of statins'
      effects beyond 10 years. In this review we will summarize the current state of
      the literature, the benefits noted to date, and the potentially accumulating,
      adverse effects of long-term statin use. 

PMID- 24899389
TI  - The first thousand days - intestinal microbiology of early life: establishing a
      symbiosis.
AB  - The development of the intestinal microbiota in the first years of life is a
      dynamic process significantly influenced by early-life nutrition. Pioneer
      bacteria colonizing the infant intestinal tract and the gradual diversification
      to a stable climax ecosystem plays a crucial role in establishing host-microbe
      interactions essential for optimal symbiosis. This colonization process and
      establishment of symbiosis may profoundly influence health throughout life.
      Recent developments in microbiologic cultivation-independent methods allow a
      detailed view of the key players and factors involved in this process and may
      further elucidate their roles in a healthy gut and immune maturation. Aberrant
      patterns may lead to identifying key microbial signatures involved in developing
      immunologic diseases into adulthood, such as asthma and atopic diseases. The
      central role of early-life nutrition in the developmental human microbiota,
      immunity, and metabolism offers promising strategies for prevention and treatment
      of such diseases. This review provides an overview of the development of the
      intestinal microbiota, its bidirectional relationship with the immune system, and
      its role in impacting health and disease, with emphasis on allergy, in early
      life. 

PMID- 24899388
TI  - Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251
      cells.
AB  - Glioblastoma is one of the most aggressive brain tumors with high morbidity and
      mortality. Hypoxia is often the common characteristic of tumor microenvironment,
      and hypoxia-inducible factor-1alpha (HIF-1alpha) is an essential factor
      regulating the migratory activity of cancer cells including glioblastoma.
      Recently, mitochondrial dynamics was found to be involved in the aggression of
      cancer cells. However, whether dynamin-related protein 1 (Drp1) contributes to
      the migration of human glioblastoma cells under hypoxia remains unknown. In the
      present study, hypoxia was found to upregulate the transcription and expression
      of Drp1, and stimulated mitochondrial fission in glioblastoma U251 cells.
      Inhibition of HIF-1alpha with echinomycin blocked hypoxia-induced expression of
      Drp1. Notably, Drp1 inhibitor Mdivi-1 efficiently attenuated hypoxia-induced
      mitochondrial fission and migration of U251 cells. In addition, three U251 stable
      cell lines expressing GFP, GFP-Drp1 and dominant negative GFP-Drp1-K38A were
      established to examine the direct role of Drp1 in hypoxia-induced migration. MTT
      assay showed that there was no significant difference in proliferation of three
      cell lines. Compared with the GFP cell line, exogenously expressed GFP-Drp1-K38A
      inhibited hypoxia-induced migration of U251 cells, while stable expression of GFP
      Drp1 enhanced the migration of U251 cells under hypoxia. Therefore, this study
      indicates the involvement of Drp1 in hypoxia-induced migration of human
      glioblastoma U251 cells, and suggests Drp1 to be a potential therapeutic target
      to suppress the aggression of glioblastoma in the future.

PMID- 24899390
TI  - The efficiency of compounds with alpha-amino-beta-mercapto-ethane group in
      protection of human serum albumin carbonylation and cross-linking with
      methylglyoxal.
AB  - alpha-Oxoaldehydes, which are produced in higher quantities in diabetes, uremia,
      oxidative stress, inflammation and aging, react with the amino, guanidine and
      thiol groups of proteins and cause the formation of advanced glycated end
      products and protein cross-linking. To prevent these reactions, the efficiency of
      low molecular mass thiols with an alpha-amino-beta-mercapto-ethane group (Cys,
      penicillamine and N-acetylcysteine (NAcCys, with a blocked amino group)) as
      scavengers of methylglyoxal, compared with glutathione (GSH) and the biguanidine
      derivative metformin, was investigated. The time courses of the reactions of the
      aforementioned compounds with methylglyoxal were assayed. The reactivity of their
      thiol and amino groups decreased in the order of Cys > penicillamine > GSH >
      NAcCys and penicillamine > Cys > GSH, respectively. Human serum albumin (HSA)
      carbonylation in the absence or presence of methylglyoxal scavengers were
      monitored by the determination of the amino, guanidine and thiol groups'
      contents, as well as by spectrofluorimetry, CD and native and SDS PAGE. Cys and
      penicillamine were highly efficient in the prevention of the carbonylation of the
      HSA-amino (for 80%) and guanidine (for 84% and 55%, respectively) groups and the
      formation of fluorescent AGEs. GSH and metformin exhibited medium efficiency
      (reduction of amino group's carbonylation for 60% and guanidine for about 30%);
      the least efficient was NAcCys. The presence of Cys, penicillamine and NAcCys led
      to an almost complete protection of the HSA-thiol group's carbonylation, whereas
      metformin was inefficient. The efficiency in the prevention of protein cross
      linking increased in the order of metformin, NAcCys < GSH < penicillamine < Cys.
      Thus, the substances with an alpha-amino-beta-mercapto-ethane group as a
      pharmacophore exhibit great potential as an efficient methylglyoxal scavengers,
      and are thus promising compounds for medicinal chemistry. In addition, they
      protect the HSA-SH group and preserve its antioxidative potential, which is very
      important for the HSA's function in vivo. 

PMID- 24899391
TI  - Effects of 21-kHz intermediate frequency magnetic fields on blood properties and
      immune systems of juvenile rats.
AB  - PURPOSE: Due to a lack of science-based evidence, we explored the effects of
      exposure to intermediate frequency magnetic fields (IF-MF) on experimental
      animals. We assessed several immunological parameters to determine the effect of
      exposure of the whole body to IF-MF. MATERIALS AND METHODS: Male Sprague-Dawley
      rats (4-5 weeks old) were divided into three groups: Cage-control, sham, and 3.8
      mT (rms) exposure groups. The animals were exposed to IF-MF at 21 kHz under fixed
      conditions in an acrylic holder. Exposure was performed for 1 h/day for 14
      consecutive days. On the 15th day following the exposure, biochemical and
      hematological parameters in blood were analyzed. The effects of the exposure on
      immunological functions such as the cytotoxic activity of lymphocytes,
      chemotactic and phagocytic activity of granulocytes, and T (cluster of
      differentiation 4 [CD4] and cluster of differentiation 8 [CD8])-cell frequency
      were also examined. RESULTS: Hematological parameters were not affected by IF-MF
      exposure. Other immune functions such as the cytotoxic activity and phagocytic
      activity were not affected. Populations of T cells after exposure also did not
      show any significant differences. In blood biochemistry, there was significant
      difference in inorganic phosphorus level between sham and exposure group.
      However, this will not induce any pathophysiological status, because they were
      still within physiological range. Overall, no significant effect by exposure of
      IF-MF was observed under our experimental conditions. CONCLUSIONS: Our results
      suggest that exposure to 21-kHz sinusoidal IF-MF at 3.8 mT for 1 h/day for 14
      days did not affect immune function in juvenile rats.

PMID- 24899392
TI  - Effect of ionizing radiation on liver protein oxidation and metabolic function in
      C57BL/6J mice.
AB  - PURPOSE: Protein oxidation in response to radiation results in DNA damage,
      endoplasmic reticulum stress/unfolded protein response, cell cycle arrest, cell
      death and senescence. The liver, a relatively radiosensitive organ, undergoes
      measurable alterations in metabolic functions following irradiation. Accordingly,
      we investigated radiation-induced changes in liver metabolism and alterations in
      protein oxidation. MATERIALS AND METHODS: C57BL/6 mice were sham irradiated or
      exposed to 8.5 Gy (60)Co (0.6 Gy/min) total body irradiation. Metabolites and
      metabolic enzymes in the blood and liver tissue were analyzed. Two-dimensional
      gel electrophoresis and OxyBlotTM were used to detect carbonylated proteins that
      were then identified by peptide mass fingerprinting. RESULTS: Analysis of serum
      metabolites revealed elevated glucose, bilirubin, lactate dehydrogenase (LDH),
      high-density lipoprotein, and aspartate aminotransferase within 24-72 h post
      irradiation. Liver tissue LDH and alkaline phosphatase activities were elevated
      24-72 h post irradiation. OxyBlotting revealed that the hepatic proteome contains
      baseline protein carbonylation. Radiation exposure increased carbonylation of
      specific liver proteins including carbonic anhydrase 1, alpha-enolase, and
      regucalcin. CONCLUSIONS: 8.5 Gy irradiation resulted in distinct metabolic
      alterations in hepatic functions. Coincident with these changes, radiation
      induced the carbonylation of specific liver enzymes. The oxidation of liver
      enzymes may underlie some radiation-induced alterations in hepatic function.

PMID- 24899393
TI  - Vitamins and glucose metabolism: The role of static magnetic fields.
AB  - PURPOSE: This review focuses on our own data and other data from the literature
      of static magnetic fields (SMF) bioeffects and vitamins and glucose metabolism.
      Three main areas of investigation have been covered: Static magnetic field and
      glucose metabolism, static magnetic field and vitamins and the role of vitamins
      on glucose metabolism. CONCLUSION: Considering these articles comprehensively,
      the conclusions are as follows: The primary cause of changes in cells after
      incubation in external SMF is disruption of free radical metabolism and elevation
      of their concentration. Such disruption causes oxidative stress leading to an
      unsteadiness of glucose level and insulin release. Moreover, based on available
      data, it was concluded that exposure to SMF alters plasma levels of vitamin A, C,
      D and E; these parameters can take part in disorder of glucose homeostasis and
      insulin release.

PMID- 24899394
TI  - Bilateral ovarian metastatic squamous cell carcinoma arising from the uterine
      cervix and eluding the Mullerian mucosa.
AB  - Bilateral ovarian metastasis from invasive squamous cell carcinoma of the cervix
      is a rare phenomenon with very few clinically significant cases described in the
      literature. Ovarian metastases when present are usually seen in association with
      bulky, advanced cervical squamous cell carcinomas with extensive involvement of
      the uterus.We describe a 48 year old woman with clinically normal cervix whose
      hysterectomy and bilateral salpingo-oophorectomy performed for abnormal uterine
      bleeding, demonstrated high grade squamous intraepithelial lesion, moderately
      differentiated squamous cell carcinoma involving the deeper stroma of the uterus
      and bilateral ovarian metastases. Gross examination of the cervical canal and the
      uterine cavity did not show tumor while well circumscribed pearly white
      metastatic deposits were distinguished within the parenchyma of both the ovaries.
      Microscopy ascertained high grade squamous intraepithelial lesion with malignant
      cells invading the deeper cervical stroma and disseminating further as
      lymphovascular tumor emboli within the myometrium of the corpus uteri without
      involving the endometrium. Both the fallopian tubes exhibited lymphovascular
      tumor emboli without epithelial involvement while the parenchyma of both the
      ovaries showed metastatic deposits.Although an isolated case of endophytic
      squamous cell carcinoma of the cervix with extensive lymphovascular invasion of
      the corpus uteri, both the fallopian tubes and bilateral ovarian deposits without
      involving either the endometrium or the tubal mucosa does not form a paradigm,
      this case brings to light the capricious behavior of cervical squamous cell
      carcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/1214687069122755.

PMID- 24899395
TI  - Footprint methods to separate N2O emission rates from adjacent paddock areas.
AB  - Using micrometeorological techniques to measure greenhouse gas emissions from
      differently treated adjacent plots is a promising avenue to verify the effect of
      mitigation strategies at the field scale. In pursuing such an approach, it is
      crucial to accurately characterize the source area of the fluxes measured at each
      sampling point. Hence, a comprehensive footprint analysis method is required so
      that emission rates can be obtained for a specific field within a biochemically
      heterogeneous area. In this study, a footprint analysis method is developed to
      estimate the emission for an experiment where the flux of N2O is measured from
      several control and treated plots. The emission rate of an individual plot is
      estimated using an inverse footprint fraction approach where the footprint
      fractions are obtained from an analytical footprint model. A numerical solution
      for obtaining the background flux for such a multiplot measurement system is also
      provided. Results of the footprint analysis method are assessed, first, by
      comparing footprint fractions obtained from both an analytical footprint model
      and a "forward" simulation of a backward Lagrangian stochastic (bLs) model; and
      second, by comparing the emission rates of a control plot obtained from the
      footprint analysis method and from the "backward" simulation of the bLs model. It
      is found that the analytical footprint fractions compare well with the values
      obtained from the bLs model (correlation coefficient of 0.58 and 0.66 within p
      value <0.001). An average of 4.3 % of the measured fluxes is found to be
      contributed by sources outside the measured area and, excluding this outside area
      contribution to the measured flux, footprint corrected emission rates within the
      defined domain are found to increase by 2.1 to 5.8 % of the measured flux. Also,
      the proposed method of emission rate estimation is found to work well under a
      wide range of atmospheric stability. 

PMID- 24899396
TI  - Climate, water and tourism: causes and effects of droughts associated with urban
      development and tourism in Benidorm (Spain).
AB  - In this paper, we analyse the relationship between climate, tourism and water in
      Benidorm (Spain), an international icon of Fordist tourism (mass tourism). In
      particular, we have studied the causes and effects of the water supply droughts
      Benidorm has suffered since becoming a major holiday destination. For this
      purpose, we consulted the local press in Benidorm over the period 1969-2003.
      Using qualitative and quantitative geographical techniques, we found that the
      water supply in the area has managed to keep up with rapidly increasing demand,
      with only occasional imbalances and periods of crisis. We focused in particular
      on the causes and effects of the water supply crisis of 1978, a moment of great
      uncertainty in the history of Benidorm as a holiday resort. We also examined the
      influence of atmospheric conditions on precipitation levels and how these
      precipitation levels affect the water supply. Our results highlight the
      importance of intense rainfall episodes associated with easterly winds, which
      provided large inputs for Benidorm's water supply system (Marina Baja Water
      Consortium). We also found that the water supply crisis of 1978 resulted in
      serious economic losses for Benidorm and damaged its image as a holiday
      destination and that the city is now less vulnerable to variations in the
      climate, as a result of its search for new water resources (both surface and
      ground water resources and from other nonconventional sources).

PMID- 24899397
TI  - Cherry blossom phenological data since the seventeenth century for Edo (Tokyo),
      Japan, and their application to estimation of March temperatures.
AB  - The changes in March mean temperatures in Edo (Tokyo), Japan, since the
      seventeenth century, were reconstructed using phenological data for the cherry
      blossoms of Prunus jamasakura deduced from old diaries and chronicles. The
      observations of the time of full blossoming and of cherry blossom viewing parties
      were acquired and used to construct a full-blossoming phenological data series
      for P. jamasakura. Phenological data from 207 of the years from 1601 to 1905 were
      used for this study. The reconstructed temperatures suggested the existence of
      two cold periods (the second half of the seventeenth century and the beginning of
      the nineteenth century), during which times the estimated March mean temperatures
      were about 4  degrees C and 5  degrees C, respectively. These two cold periods at
      Edo coincided with those reconstructed at Kyoto in previous studies. These cold
      periods coincided with two less extreme periods, the Maunder and Dalton minima,
      in the long-term solar variation cycle. 

PMID- 24899398
TI  - Nurses' stories of a 'Fairy Garden' healing haven for sick children.
AB  - AIMS AND OBJECTIVES: To report on the stories of registered nurses and nurse
      administrators in a Thai hospital that recently constructed a healing haven
      environment called a 'Fairy Garden' to support the formal and informal activities
      of sick children. BACKGROUND: While there has been some research into healing
      environments in health for adults, there has been no qualitative research into
      healing environments such as natural gardens for children. DESIGN: Narrative
      inquiry was selected to capture the holistic notion of the participant's
      experience. Clandinin's narrative inquiry framework involving three dimensions
      sociality, space and temporality was used to analyse the data. METHODS: Eight
      nurses (including two head nurses, three ward nurses and three nurse
      administrators) were interviewed in three separate focus groups between November
      2011-June 2012. RESULTS: Findings included storylines/threads of happiness,
      relaxation and calmness, imagination, spirituality and cooperation in reporting
      observed responses of sick children to the 'Fairy Garden'. Importantly, play was
      seen as a distractor from the children's pain and illness, with the children's
      ward no longer viewed as simply a clinical hospital site. Rather the
      opportunities that were afforded to children to interact with the 'Fairy Garden'
      environment expanded their hospital experience to include play, social
      interaction and educational activities. CONCLUSION: The Nurses' stories capture
      numerous storylines and threads in which the 'Fairy Garden' becomes an
      environment beyond the constraints of the hospital ward. Storylines indicate
      increased acceptance and adherence to treatment as the 'Fairy Garden' opens up
      alternatives for children, especially those children long term in the hospital.
      Children exhibit behaviours that suggest the 'Fairy Garden' supports psycho
      social and physical benefits that improve their hospital stay and provide
      potential for improved clinical outcomes. RELEVANCE TO CLINICAL PRACTICE:
      Designed hospital environments need to consider the addition of natural and
      activity spaces to support sick children and their families. Reports from nurses
      caring for children indicate benefits of the natural environment outside the
      clinical area.

PMID- 24899401
TI  - The obstetric history: personal and family.

PMID- 24899400
TI  - Strategy for automated NMR resonance assignment of RNA: application to 48
      nucleotide K10.
AB  - A procedure is presented for automated sequence-specific assignment of NMR
      resonances of uniformly [(13)C, (15)N]-labeled RNA. The method is based on a
      suite of four through-bond and two through-space high-dimensional automated
      projection spectroscopy (APSY) experiments. The approach is exemplified with a
      0.3 mM sample of an RNA stem-loop with 48 nucleotides, K10, which is responsible
      for dynein-mediated localization of Drosophila fs(1)K10 mRNA transcripts. The
      automated analysis of the APSY data led to highly accurate and precise 3- to 4
      dimensional peak lists. They provided a reliable basis for the subsequent
      sequence-specific resonance assignment with the algorithm FLYA and resulted in
      the fully automated resonance assignment of more than 80 % of the resonances of
      the (13)C-(1)H moieties at the 1', 2', 5, 6, and 8 positions in the nucleotides.
      The procedure was robust with respect to numerous impurity peaks, low
      concentration of this for NMR comparably large RNA, and structural features such
      as a loop, single-nucleotide bulges and a non-Watson-Crick wobble base pairs.
      Currently, there is no precise chemical shift statistics (as used by FLYA) for
      RNA regions which deviate from the regular A-form helical structure. Reliable and
      precise peak lists are thus required for automated sequence-specific assignment,
      as provided by APSY. 

PMID- 24899399
TI  - Smoking in cars in England: a study of school students in an English city.
AB  - BACKGROUND: Exposure to secondhand smoke is associated with an increased risk of
      adverse health effects among children. Although smoking in the home is an
      established major source of exposure, less is known about rules on smoking in
      cars. METHODS: In a survey including a sample of secondary school students in
      Nottingham (UK) in 2012, participants were asked whether smoking was allowed in
      the family car, and how often the respondent travelled in a car in which smoking
      was allowed. Rules on smoking in cars were investigated in relation to socio
      demographic variables and whether children had ever smoked themselves using
      logistic regression. RESULTS: Of 4,190 students aged 11-16 who provided data,
      approximately 12% reported that smoking was allowed in their family car and 35%
      that they travelled in a car where smoking was allowed at least sometimes.
      Absence of smoke free rules in the family car was more likely to be reported by
      children from more disadvantaged families, if parents and friends were smokers
      and if smoking was allowed in the main home. These factors, and having a sibling
      who smokes, were also independently associated with an increased risk of
      travelling in a car in which smoking was allowed at least sometimes. Respondents
      who were not protected from secondhand smoke in the car were also more likely to
      have ever smoked (adjusted odds ratio 1.59, 95% CI 1.18-2.14). CONCLUSIONS:
      Absence of smoke free rules in a family car and travelling in a car where smoking
      was allowed was relatively common among secondary school students, was strongly
      related to social disadvantage and a higher risk of smoking experimentation.
      Measures to prevent such exposure are therefore indicated.

PMID- 24899402
TI  - On the hydrostannylation of aryl propargylic alcohols and their derivatives:
      remarkable differences in both regio- and stereoselectivity in radical- and
      nonradical-mediated transformations.
AB  - Herein, we describe a highly regio- and stereoselective radical-mediated and
      molecular-oxygen (O2 )-dependent hydrostannylation of phenyl propargylic alcohols
      and their derivatives. There is a significant steric effect on the
      stereoselectivity of the tin-radical addition. Further, the uncatalyzed regio-
      and stereoselective hydrostannylation of aryl propargylic alcohols with nBu3 SnH
      and Ph3 SnH is also described and occurs with near titration kinetics. Although
      the uncatalyzed addition with nBu3 SnH gave a remarkable gamma-regioselectivity
      irrespective of the electronic nature of the aryl moiety, addition with Ph3 SnH
      appears to be driven by the electronic nature of the aryl alkynes. 

PMID- 24899404
TI  - Acute rash and ankle pain in a young woman.

PMID- 24899403
TI  - Diverse roles of PtrDUF579 proteins in Populus and PtrDUF579-1 function in
      vascular cambium proliferation during secondary growth.
AB  - DUF579 (domain of unknown function 579) family proteins contain a DUF579 domain
      structure but vary greatly in their overall sequence similarity. Several DUF579
      proteins have been found to play a role in cell wall biosynthesis in Arabidopsis,
      while DUF579 family genes have not yet been systematically investigated in
      Populus. In this study, the Populus DUF579 family proteins were found to be
      localized in different cell types and subcellular locations. The diverse
      expression patterns of the proteins indicate that they may perform different
      functions in Populus. Among the DUF579 family members, PtrDUF579-1 is found to be
      specifically expressed in vascular cambium zone cells where it is localized in
      the Golgi apparatus. Suppression of PtrDUF579-1 expression reduced plant height
      and stem diameter size. Cambium cell division and xylem tissue growth was
      inhibited while secondary cell wall formation was unchanged in PtrDUF579-1
      suppressed plants. Cell walls analysis showed that the composition of the pectin
      fraction of the cambium cell wall was altered while other polysaccharides were
      not affected in PtrDUF579-1 suppressed plants. This observation suggest cambium
      expressed PtrDUF579-1 may affect cell wall biosynthesis and be involved in
      cambium cell proliferation in Populus. Overall, DUF579 family proteins play a
      diverse set of roles in Populus. 

PMID- 24899405
TI  - A recurrent p.M157R mutation of keratin 9 gene in a Chinese family with
      epidermolytic palmoplantar keratoderma and literature review.

PMID- 24899406
TI  - Congenital hypothyroidism associated with congenital diaphragmatic hernia.

PMID- 24899407
TI  - Upregulation of the putative oncogene COTE1 contributes to human
      hepatocarcinogenesis through modulation of WWOX signaling.
AB  - Family with sequence similarity 189, also known as COTE1, has been found to be
      significantly upregulated in hepatocellular carcinoma (HCC) specimens and cell
      lines and is associated with tumor size and differentiation. Furthermore, COTE1
      contributes to hepatocellular carcinogenesis. The overexpression of COTE1
      enhanced in vitro cell viability and colony formation in soft agar, and in vivo
      tumorigenicity of HCC-derived Focus and Huh7 cells. In contrast, COTE1 knockdown
      via RNAi markedly suppressed these phenotypes in YY-8103 and WRL-68 HCC cell
      lines. Mechanistic analyses indicated that COTE1 physically associated with WW
      domain-containing oxidoreductase (WWOX) and modulated WWOX tyrosine
      phosphorylation. The ectopic overexpression of COTE1 inhibited the WWOX-p53
      signaling pathway by reducing the phosphorylation of WWOX at the Tyr33 residue in
      Focus cells. Conversely, COTE1 silencing activated tyrosine 33 phosphorylation of
      WWOX and induced WWOX-p53 mediated mitochondrial apoptosis in WRL-68 cells. In
      addition, COTE1 upregulation in Huh7 cells blocked the WWOX-cyclin D1 pathway via
      dephosphorylation of WWOX Tyr287, stimulating cell cycle progression whereas
      phosphorylation of Tyr287 of WWOX induced by COTE1 silencing resulted in
      activation of WWOX-cyclin D1 signaling, leading to cell cycle arrest in YY-8103
      cells. Together, our findings suggest that the cytoplasmic protein COTE1
      contributes to HCC tumorigenesis by regulating cell proliferation through the
      modulation of WWOX signaling. 

PMID- 24899409
TI  - The link between hypertension and pathological scarring: does hypertension cause
      or promote keloid and hypertrophic scar pathogenesis?
AB  - Pathological scars, namely, keloids and hypertrophic scars (HSs), are caused by
      excessive cutaneous wound healing that is characterized by histological
      extracellular matrix (ECM) accumulation, clinically relevant irritating symptoms,
      and frequent recurrence after surgical excision. To date, there are few effective
      and specific treatments. This partly reflects the poor understanding of the
      etiology of these scars and the lack of a suitable animal model. Systemic
      hypertension has been suggested to participate in pathological scarring. The
      evidence that supports this hypothesis is reviewed here. Thus, hypertension
      associates with changes that resemble the aberrant cutaneous wound-healing phases
      that characterize pathological scar development. It also associates with
      profibrotic functional changes in the cells that constitute keloids and HSs
      (endothelial cells, pericytes/myofibroblasts, dermal fibroblasts, and mast cells)
      and profibrotic ECM remodeling. These hypertension-associated changes are
      mediated to some extent by inflammation, hypoxia, and the angiotensin/renin
      angiotensin-aldosterone system. Thus, hypertension may be an aggravating/risk
      factor for keloids and HSs. This will help to identify patients who are prone to
      heavy scars after surgery or postsurgical recurrence. Moreover, pharmacological
      agents for the prophylaxis and treatment of hypertension-induced fibrosis in
      other organs may also be useful for keloids/HSs. 

PMID- 24899408
TI  - The self-sorting behavior of circular helicates and molecular knots and links.
AB  - We report on multicomponent self-sorting to form open circular helicates of
      different sizes from a primary monoamine, Fe(II) ions, and dialdehyde ligand
      strands that differ in length and structure by only two oxygen atoms. The
      corresponding closed circular helicates that are formed from a diamine--a
      molecular Solomon link and a pentafoil knot--also self-sort, but up to two of the
      Solomon-link-forming ligand strands can be accommodated within the pentafoil knot
      structure and are either incorporated or omitted depending on the stage that the
      components are mixed.

PMID- 24899410
TI  - Assessment of quality-of-life outcomes after surgery for nasal polyposis with the
      DyNaChron questionnaire.
AB  - This prospective study assesses outcomes at 6 weeks and 7 months after radical
      ethmoid surgery in 65 patients with nasal polyposis using a new and detailed
      instrument, the DyNaChron questionnaire, which was filled in the day prior to
      surgery and at 6 weeks and 7 months after surgery at follow-up visits. Before
      surgery, the leading bothersome symptoms were olfactory disturbances (7.74 +/-
      2.81) and nasal obstruction (6.66 +/- 2.28). After surgery (6th week and 7th
      month), there was a clear improvement of all symptoms including nasal
      obstruction, olfactory disturbances, anterior rhinorrhea, postnasal discharge,
      facial pain/headache and cough in comparison to baseline (p < 0.0001). Nasal
      obstruction was the most improved symptom (effect size of 2.24). At 7th post
      operative month, the sense of smell continued to improve slightly. By contrast,
      the postnasal discharge score that was significantly improved at 6th post
      operative week tended to worsen at 7 months (p = 0.0045). Before surgery, strong
      psychosocial impacts were observed in association with nasal obstruction and
      anterior rhinorrhea. The physical impacts of each symptom were proportionally
      correlated to the symptom score before and after surgery. The quality of life
      (QOL) related to each symptom was clearly better at 6 weeks and remained steady
      at 7 months after surgery. In conclusion, olfactory disorders and postnasal
      rhinorrhea were the main remaining symptoms after sinus surgery despite a global
      improvement of symptoms and quality of life. The earlier time point to stabilize
      QOL outcomes of endoscopic sinus surgery could be suggested at 6 weeks after
      surgery.

PMID- 24899411
TI  - Labyrinthine fenestration for stapes fixation in chronic ear disease others than
      otosclerosis.
AB  - The objective of this study is to assess the results of labyrinthine fenestration
      for fixed stapes in chronic ear disease. Using a prospective database, pre- and
      postoperative audiometric data from patients undergoing labyrinthine fenestration
      for fixation of the stapes in chronic ear disease others than otosclerosis
      between 2002 and 2012 were evaluated. Twenty-three labyrinthine fenestrations in
      chronic ear disease were performed (17 malleo-stapedotomies, 4 incus
      stapedotomies, 1 neo-malleus-stapedotomy, 1 TORP-stapedotomy). Overall, the mean
      short-term (2 months) and long-term (42 months) postoperative air-bone gap (0.5-3
      kHz) were 17.5 and 16.5 dB, respectively; long-term air-bone gap of <20 dB was
      obtained in 73 % of patients. There was no significant difference in air-bone gap
      closure between tympanosclerotic and post inflammatory osteogenic fixation of the
      stapes (p = 0.267). Hearing benefit success using the 'Belfast rule of the thumb'
      was achieved in 48 %. Normal bilateral hearing was achieved in 17 % and bilateral
      symmetric hearing impairment in 26 %. Only in 4 %, bone conduction worsened by
      more than 5 dB. Labyrinthine fenestration is an option in selected cases of
      stapes fixation in chronic ear disease and provides hearing gain without
      significant risk for sensorineural hearing loss. In those already selected cases,
      hearing benefit success 'Belfast rule of the thumb' is achieved only in half of
      the cases. This and the possible alternatives, should therefore be discussed
      preoperatively.

PMID- 24899412
TI  - Disposable electrochemical sensor to evaluate the phytoremediation of the aquatic
      plant Lemna minor L. toward Pb(2+) and/or Cd(2+).
AB  - In this work a miniaturized and disposable electrochemical sensor was developed
      to evaluate the cadmium and lead ion phytoremediation potential by the floating
      aquatic macrophyte Lemna minor L. The sensor is based on a screen-printed
      electrode modified "in-situ" with bismuth film, which is more environmentally
      friendly than the mercury-based sensor usually adopted for lead and cadmium ion
      detection. The sensor was coupled with a portable potentiostat for the
      simultaneous measurement of cadmium and lead ions by stripping analysis. The
      optimized analytical system allows the simultaneous detection of both heavy
      metals at the ppb level (LOD equal to 0.3 and 2 ppb for lead and cadmium ions,
      respectively) with the advantage of using a miniaturized and cost-effective
      system. The sensor was then applied for the evaluation of Pb(2+) or/and Cd(2+)
      uptake by measuring the amount of the heavy metals both in growth medium and in
      plant tissues during 1 week experiments. In this way, the use of Lemna minor
      coupled with a portable electrochemical sensor allows the set up of a model
      system able both to remove the heavy metals and to measure "in-situ" the
      magnitude of heavy metal removal. 

PMID- 24899413
TI  - Polyenylcyclopropane carboxylic esters with high insecticidal activity.
AB  - BACKGROUND: Pyrethroids are synthetic derivatives of naturally occurring
      pyrethrum. These molecules are widely used in agriculture for ant, fly and
      mosquito control and for lawn and garden care. Pyrethroids are the optically
      active esters of 2,2-dimethyl-3-(2-methylpropenyl)-cyclopropane carboxylic acid,
      also known as chrysanthemic acid. However, their intense use has resulted in the
      development of resistance in many insect species. Herein, specific structural
      modifications of the pyrethroid scaffold and their effect on insecticidal
      activity, especially on resistant pests strains, are reported. RESULTS: The
      exposure to (1R)-trans-(E/Z)-2,3,5,6-tetrafluorobenzyl-3-(buta-1,3-dienyl)-2,2
      dimethyl cyclopropanecarboxylate and its diastereomers produced 100% mortality in
      yellow fever mosquitoes (Aedes aegypti), house mosquitoes (Culex
      quinquefasciatus) and houseflies (Musca domestica). Moreover, this compound
      provided complete knockdown within 15 min of exposure against cockroaches
      (Blattella germanica) and maintained an excellent knockdown activity at 10 days
      after treatment. CONCLUSION: Novel pyrethroid derivatives obtained from 2,2
      dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylic acid are described. These
      derivatives display high insecticidal activity, a wide spectrum of action and no
      toxicity towards mammalians. The proposed synthetic procedures are highly
      efficient and inexpensive, and therefore suitable for industrial scale-up.

PMID- 24899414
TI  - p40 immunoperoxidase staining of anorectal carcinomas.

PMID- 24899415
TI  - Hemagglutination assay for influenza virus.
AB  - The hemagglutination assay (HA) is a tool used to screen cell culture isolates or
      amnioallantoic fluid harvested from embryonated chicken eggs for hemagglutinating
      agents, such as type A influenza. The HA assay is not an identification assay, as
      other agents also have hemagglutinating properties. Live and inactivated viruses
      are detected by the HA test. Amplification by virus isolation in embryonated
      chicken eggs or cell culture is typically required before HA activity can be
      detected from a clinical sample. The test is, to some extent, quantitative as 1
      hemagglutinating unit (HAU) is equal to approximately 5-6 logs of virus. It is
      inexpensive and relatively simple to conduct. Several factors (quality of chicken
      erythrocytes, laboratory temperature, laboratory equipment, technical expertise
      of the user) may contribute to slight differences in the interpretation of the
      test each time it is run. This chapter describes the methods validated and used
      by the US National Veterinary Services Laboratories for screening and
      identification of hemagglutinating viruses. 

PMID- 24899416
TI  - Hemagglutination-inhibition assay for influenza virus subtype identification and
      the detection and quantitation of serum antibodies to influenza virus.
AB  - Hemagglutination-inhibition (HI) assay is a classical laboratory procedure for
      the classification or subtyping of hemagglutinating viruses. For influenza virus,
      HI assay is used to identify the hemagglutinin (HA) subtype of an unknown isolate
      or the HA subtype specificity of antibodies to influenza virus. Since the HI
      assay is quantitative it is frequently applied to evaluate the antigenic
      relationships between different influenza virus isolates of the same subtype. The
      basis of the HI test is inhibition of hemagglutination with subtype-specific
      antibodies. The HI assay is a relatively inexpensive procedure utilizing standard
      laboratory equipment, is less technical than molecular tests, and is easily
      completed within several hours. However when working with uncharacterized viruses
      or antibody subtypes the library of reference reagents required for identifying
      antigenically distinct influenza viruses and or antibody specificities from
      multiple lineages of a single hemagglutinin subtype requires extensive laboratory
      support for the production and optimization of reagents. 

PMID- 24899417
TI  - Neuraminidase-inhibition assay for the identification of influenza A virus
      neuraminidase virus subtype or neuraminidase antibody specificity.
AB  - The neuraminidase-inhibition (NI) assay is a laboratory procedure for the
      identification of the neuraminidase (NA) glycoprotein subtype in influenza
      viruses or the NA subtype specificity of antibodies to influenza virus. A
      serological procedure for subtyping the NA glycoprotein is critical for the
      identification and classification of avian influenza (AI) viruses. The
      macroprocedure was first described in 1961 by Aminoff and was later modified to a
      microtiter plate procedure (micro-NI) by Van Deusen et al. (Avian Dis 27:745-750,
      1983). The micro-NI procedure reduces the quantity of reagents required, permits
      the antigenic classification of many isolates simultaneously, and eliminates
      spectrophotometric interpretation of results. Although, the macro-NI has been
      shown to be more sensitive than the micro-NI, the micro-NI test is very suitable
      for testing sera for the presence of NA antibodies and has proven to be a
      practical and rapid method for virus classification. This chapter provides an
      overview of the USDA validated micro-NI procedure for the identification of
      subtype-specific NA in AIV and antibodies. 

PMID- 24899418
TI  - Reverse genetics of influenza virus.
AB  - Reverse genetics is the creation of a virus from a full-length cDNA copy of the
      viral genome, referred to as an "infectious clone," and is one of the most
      powerful genetic tools in modern virology. Since its development in 1999, plasmid
      based reverse genetics has been effectively applied to numerous aspects of
      influenza studies which include revolutionizing the production of seasonal and
      pandemic influenza vaccine seed strains. Although continual improvement in
      reverse genetics system is being made in different laboratories for the efficient
      rescue of the influenza virus, the basic concept of synthesizing viral RNA using
      RNA polymerase I remains the same. Coupled with in vitro mutagenesis, reverse
      genetics can be applied widely to accelerate progress in understanding the
      influenza virus life cycle, the generation of customized vaccine seed strains,
      development of live-attenuated vaccines, and the use of influenza virus as
      vaccine and gene delivery vectors. 

PMID- 24899419
TI  - Immunohistochemical staining of influenza virus in tissues.
AB  - Immunohistochemical methods are commonly used for studying the pathogenesis of
      influenza A virus by allowing the identification of sites of replication of the
      virus in infected tissues and the correlation with the histopathological changes
      observed. In this chapter, the materials and methods for performing
      immunohistochemical detection of influenza virus antigens in tissues are
      provided. The technique involves the following steps: heat-induced antigen
      retrieval; binding of a primary antibody to the virus antigen; antibody-antigen
      complex binding by a biotinylated secondary antibody; and binding of an enzyme
      streptavidin conjugate. The enzyme is then visualized by application of the
      substrate chromogen solution to produce a colorimetric end product. Visualization
      of influenza virus antigen in tissues is based on chromogen deposition in the
      nucleus and cytoplasm of infected cells. 

PMID- 24899420
TI  - A brief introduction to avian influenza virus.
AB  - Avian influenza virus (AIV) causes a disease of high economic importance for
      poultry production worldwide. The earliest recorded cases of probable high
      pathogenicity AIV in poultry were reported in Italy in the 1870s, and avian
      influenza has been recognized in domestic poultry through the modern era of
      poultry production. Approaches to control vary widely, but elimination of the
      disease in poultry is a common goal. The basics of AIV biology, clinical disease,
      molecular aspects, and AIV detection are briefly reviewed. 

PMID- 24899421
TI  - Wild bird surveillance for avian influenza virus.
AB  - Avian influenza (AI) viruses have been isolated from a wide-diversity of free
      living avian species representing several taxonomic orders. Isolations are most
      frequently reported from aquatic birds in the Orders Anseriformes and
      Charadriiformes, which are believed to be the primordial reservoirs for all AI
      viruses. Since first recognized in the late 1800s, AI viruses have been an
      important agent of disease in poultry and, occasionally, of non-gallinaceous
      birds and mammals. However, recent infections of humans with AI viruses,
      including highly pathogenic avian influenza (HPAI) H5N1 virus and low
      pathogenicity H7N9 AI virus in China during 2013, have increased the awareness of
      their potential to impact agricultural, wildlife, and public health. This chapter
      is intended to give general concepts and guidelines for planning and implementing
      surveillance programs for AI virus in wild birds. 

PMID- 24899422
TI  - Avian influenza virus sample types, collection, and handling.
AB  - Successful detection of avian influenza (AI) virus, viral antigen, nucleic acid,
      or antibody is dependent upon the collection of the appropriate sample type, the
      quality of the sample, and the proper storage and handling of the sample. The
      diagnostic tests to be performed should be considered prior to sample collection.
      Sera are acceptable samples for ELISA or agar gel precipitin tests, but not for
      real-time RT-PCR. Likewise, swabs and/or tissues are acceptable for real-time RT
      PCR and virus isolation. The sample type will also depend on the type of birds
      that are being tested; although it is optimal to collect both oropharyngeal and
      cloacal swabs, oropharyngeal swabs should be collected from gallinaceous poultry
      and cloacal swabs should be collected from waterfowl. In addition to collecting
      the appropriate sample for the tests to be performed, selecting the right
      materials for sample collection (i.e., type of swab) is very important. This
      chapter outlines the collection of different specimen types and procedures for
      proper specimen handling. 

PMID- 24899423
TI  - Avian influenza virus RNA extraction.
AB  - The efficient extraction and purification of viral RNA is critical for down
      stream molecular applications whether it is the sensitive and specific detection
      of virus in clinical samples, virus gene cloning and expression, or
      quantification of avian influenza (AI) virus by molecular methods from
      experimentally infected birds. Samples can generally be divided into two types;
      enriched (e.g. virus stocks) and clinical. Clinical type samples, which may be
      tissues or swab material, are the most difficult to process due to the complex
      sample composition and possibly low virus titers. In this chapter two well
      established procedures for the isolation of AI virus RNA from common clinical
      specimen types and enriched virus stocks for further molecular applications will
      be presented. 

PMID- 24899424
TI  - Avian influenza virus detection and quantitation by real-time RT-PCR.
AB  - Real-time RT-PCR (rRT-PCR) has been used for avian influenza virus (AIV)
      detection since the early 2000s for routine surveillance, outbreak assessment and
      for research. Some of the advantages of rRT-PCR are: high sensitivity, high
      specificity, rapid time-to-result, scalability, cost, and its inherently
      quantitative nature. Furthermore, rRT-PCR can be used with numerous sample types,
      is less expensive than virus isolation in chicken embryos, and since infectious
      virus is inactivated early during processing, biosafety and bio-security are also
      easier to maintain. However, the high genetic variability of AIV may decrease
      sensitivity and increases the chances of a false negative result. This chapter
      provides an overview of the USDA validated rRT-PCR procedure for the detection of
      type A influenza. 

PMID- 24899425
TI  - Influenza subtype identification with molecular methods.
AB  - Gene sequencing and RT-PCR based methods are the molecular alternative to
      serology for the identification of influenza virus hemagglutinin and
      neuraminidase antigenic subtypes. Compared to serology both RT-PCR and sequencing
      are preferred subtyping methods because of the number of reference reagents which
      need to be prepared for serological methods and results of molecular methods are
      often easier to interpret. The best method to utilize will depend on the goals of
      the work being conducted and the resources available. The salient features and
      basic outline of workflow for subtype identification by molecular methods will be
      discussed. 

PMID- 24899426
TI  - Avian influenza virus isolation, propagation, and titration in embryonated
      chicken eggs.
AB  - Avian influenza virus and some mammalian influenza A viruses are usually
      isolated, propagated, and titrated in embryonated chicken eggs (ECE). Most any
      sample type can be accommodated for culture with appropriate processing.
      Isolation may also be accomplished in cell culture particularly if mammalian
      lineage isolates are suspected, for example, swine influenza in turkey specimens.
      Culture is highly sensitive, but is not specific for influenza A, which may be an
      advantage because a sample may be screened for several agents at once. Once an
      agent is isolated in culture, the presence of influenza viruses is confirmed with
      any of several assays. The methods for propagating virus isolates in ECE are
      described. 

PMID- 24899427
TI  - Agar gel immunodiffusion assay to detect antibodies to Type A influenza virus.
AB  - The agar gel immunodiffusion (AGID) test is used to detect antibodies to Type A
      influenza group-specific antigens, i.e., the ribonucleoprotein (RNP) and matrix
      (M) proteins. Therefore, this test will detect antibodies to all influenza A
      virus subtypes. AGID is commonly used to screen poultry flocks for avian
      influenza virus infection. The AGID is a simple and economical serological test.
      All serological testing has its advantages and disadvantages which should be
      considered before choosing the optimal test for the laboratory needs. Each
      laboratory must evaluate the laboratory's resources, the volume of testing, the
      goal of testing, how the test results are used and what types of samples are
      being tested in order to select the optimal test. 

PMID- 24899428
TI  - Detection of influenza A antibodies in avian serum samples by ELISA.
AB  - ELISA assays are a fast and relatively inexpensive way to screen sera for
      antibodies to avian influenza virus. Commercial ELISA kits are available, and
      although they are more expensive, they provide a ready-to-use assay with good
      quality control. Various sample types can be processed for ELISA: serum, plasma,
      egg yolk, blood collected on filter paper. Quality samples are critical to
      accurate results. The basics of AIV antibody ELISA, sample processing, results
      interpretation, and troubleshooting are discussed. 

PMID- 24899429
TI  - Conducting influenza virus pathogenesis studies in avian species.
AB  - Avian infection studies with influenza A virus are an important means of
      assessing host susceptibility, viral pathogenesis, host responses to infection,
      mechanisms of transmission, and viral pathotype. Complex systems and natural
      settings may also be explored with carefully designed infection studies. In this
      chapter, we explore the elements of infection studies, general guidelines for
      choosing a virus to use, host selection, and many aspects of study design. 

PMID- 24899430
TI  - Laboratory methods for assessing and licensing influenza vaccines for poultry.
AB  - Avian influenza vaccines for poultry are based on hemagglutinin proteins, and
      protection is specific to the vaccine subtype. Over 113 billion doses have been
      used between 2002 and 2010 for high pathogenicity avian influenza control. No
      universal vaccines are currently available. The majority of avian influenza
      vaccines are inactivated whole influenza viruses that are grown in embryonating
      eggs, inactivated, emulsified in oil adjuvant systems, and injected into
      chickens. Live virus-vectored vaccines such as recombinant viruses of fowl pox,
      Newcastle disease, herpesvirus of turkeys and duck enteritis containing inserts
      of avian influenza virus hemagglutinin genes have been used on a more limited
      basis. In studies to evaluate vaccine efficacy and potency, the protocol design
      and its implementation should address the biosafety level needed for the work,
      provide information required for approval by Institutional Biosafety and Animal
      Care Committees, contain information on seed strain selection, provide needed
      information on animal subjects and their relevant parameters, and address the
      selection and use of challenge viruses. Various metrics have been used to
      directly measure vaccine induced protection. These include prevention of death,
      clinical signs, and lesions; prevention of decreases in egg production and
      alterations in egg quality; quantification of the reduction in virus replication
      and shedding from the respiratory tract and gastrointestinal tracts; and
      prevention of contact transmission in in vivo poultry experiments. In addition,
      indirect measures of vaccine potency and protection can be developed and
      validated against the direct measures and include serological assays in
      vaccinated poultry and assessment of the content of hemagglutinin antigen in the
      vaccine. These indirect assessments of protection are useful in determining if
      vaccine batches have a consistent ability to protect. For adequate potency,
      vaccines should contain 50 mean protective doses of antigen, which corresponds to
      0.3-7.8 MUg of hemagglutinin protein, depending on immunogenicity of individual
      seed strains. 

PMID- 24899431
TI  - Detection of cell-mediated immune response to avian influenza viruses.
AB  - The measurement of cell-mediated immunity (CMI) is critical to understanding the
      role and regulation of avian lymphocytes following avian influenza virus (AIV)
      infection. While these different cell types have distinctly different modes of
      action in terms of contributions to protection, they account for the majority of
      adaptive immunity induced following infection or vaccination. Although the
      ability to measure CMI has steadily improved over the last few years, few studies
      have examined its role in protection of birds against AIV. The increasing
      availability of monoclonal antibodies recognizing various avian cell-associated
      antigens has made this technique more specific and informative. 

PMID- 24899432
TI  - Characterization of cytokine expression induced by avian influenza virus
      infection with real-time RT-PCR.
AB  - Knowledge of how birds react to infection from avian influenza virus is critical
      to understanding disease pathogenesis and host response. The use of real-time (R)
      RT-PCR to measure innate immunity, including cytokine and interferon gene
      expression, has become a standard technique employed by avian immunologists
      interested in examining these responses. This technique utilizes nucleotide
      primers and fluorescent reporter molecules to measure amplification of the gene
      of interest. The use of RRT-PCR negates the need for northern blot analysis or
      DNA sequencing. It is simple, specific and sensitive for the gene of interest.
      However, it is dependent on knowing the target sequence prior to testing so that
      the optimal primers can be designed. The recent publication of genomic sequences
      of Gallus gallus, Meleagris gallopavo, and Anas platyrhynchos species makes it
      possible to measure cytokine expression in chicken, turkey, and duck species,
      respectively. Although these tests do not measure functionally expressed protein,
      the lack of antibodies to identify and quantify avian cytokines from different
      avian species makes this technique critical to any characterization of innate
      immune responses through cytokine and interferon activation or repression. 

PMID- 24899433
TI  - Newcastle disease virus detection and differentiation from avian influenza.
AB  - Newcastle disease (ND) is a contagious and often fatal disease that affects over
      250 bird species worldwide, and is caused by infection with virulent strains of
      avian paramyxovirus-1 (APMV-1) of the family Paramyxoviridae, genus Avulavirus.
      Infections of poultry with virulent strains of APMV-1 (Newcastle disease virus)
      are reportable to the World Organization for Animal Health (OIE). Vaccination of
      poultry species is a key measure in the control of ND. Other APMV-1 viruses of
      low virulence, which are not used as vaccines, are also often isolated from wild
      bird species. The APMV-1 virus, like avian influenza virus (AIV), is a
      hemagglutinating virus (HA) and able to agglutinate chicken red blood cells
      (RBC). Because the clinical presentation of ND can be difficult to distinguish
      from disease caused by AIV, techniques for differential diagnosis are essential,
      as well as the ability to detect mixed infections. When an HA positive virus is
      detected from virus isolation, additional assays can be performed to determine
      which virus is present. Both antigenic and molecular methods are necessary as
      some virulent ND viruses from cormorants in the USA after 2002 have lost their
      ability to hemagglutinate chicken RBC and molecular methods are needed for
      identification. 

PMID- 24899434
TI  - A brief introduction to influenza A virus in swine.
AB  - Influenza A viruses (IAV) of the Orthomyxoviridae virus family cause one of the
      most important respiratory diseases in pigs as well as humans. Repeated outbreaks
      and rapid spread of genetically and antigenically distinct IAVs represent a
      considerable challenge for animal production and public health. This overlap
      between human and animal health is a prime example of the "One Health" concept.
      Although only subtypes of H1N1, H1N2, and H3N2 are endemic in swine around the
      world, considerable diversity can be found not only in the hemagglutinin (HA) and
      neuraminidase (NA) genes, but in the other 6 genes as well. Human and swine IAV
      have demonstrated a particular propensity for interspecies transmission in the
      past century, leading to regular and sometimes sustained, incursions from man to
      pig and vice versa. The diversity of IAV in swine remains one of the critical
      challenges in diagnosis and control of this important pathogen for swine health,
      and in turn contributes to a significant public health risk. 

PMID- 24899435
TI  - Sample types, collection, and transport for influenza A viruses of swine.
AB  - Detection of influenza A virus (IAV), viral antigen, nucleic acid, or antibodies
      in swine is dependent upon the collection of the appropriate sample type, the
      quality of the sample, and the proper storage and handling of the sample. The
      diagnostic tests to be performed should be considered prior to sample collection.
      Sera are acceptable samples for ELISA or hemagglutination inhibition tests, but
      not for real-time RT-PCR. Likewise, swabs and/or tissues are acceptable for real
      time RT-PCR and virus isolation. The sample type will also depend on the age of
      swine that are being tested; oral fluids can be successfully collected from
      weaned pigs usually greater than 3 weeks of age, whereas nasal swabs should be
      collected from suckling pigs in the first weeks of life. This chapter outlines
      the collection of different specimen types and procedures for proper specimen
      handling. 

PMID- 24899436
TI  - Isolation of swine influenza virus in cell cultures and embryonated chicken eggs.
AB  - Influenza virus isolation is a procedure to obtain a live and infectious virus
      that can be used for antigenic characterization, pathogenesis investigation, and
      vaccine production. Embryonated chicken egg inoculation is traditionally
      considered the "gold standard" method for influenza virus isolation and
      propagation. However, many primary cells and continuous cell lines have also been
      examined or developed for influenza virus isolation and replication.
      Specifically, swine influenza virus (SIV) isolation and propagation have been
      attempted and compared in embryonated chicken eggs, some primary porcine cells,
      and a number of continuous cell lines. Currently Madin-Darby canine kidney (MDCK)
      cells remain the most commonly used cell line for isolation, propagation, and
      titration of SIV. Virus isolation in embryonated chicken eggs or in different
      cell lines offers alternative approaches when SIV isolation in MDCK cells is
      unsuccessful. Nasal swabs, lung tissues, and oral fluids are three major specimen
      types for SIV isolation. In this chapter, we describe the procedures of sample
      processing, SIV isolation in MDCK cells and in embryonated chicken eggs, as well
      as methods used for confirming the virus isolation results. 

PMID- 24899437
TI  - RNA extraction from swine samples and detection of influenza A virus in swine by
      real-time RT-PCR.
AB  - Real-time RT-PCR (rRT-PCR) assays are currently the method of choice in many
      laboratories for the detection and subtyping of influenza A virus (IAV) in swine.
      Traditionally, nasal swabs and lung tissues (sometimes broncho-alveolar lavage
      and tracheal tissues) are the primary specimens for IAV testing. However, oral
      fluids are becoming more common for IAV prognostic profiling. In this chapter, we
      describe (1) procedures of RNA extraction from the common clinical specimens, (2)
      two rRT-PCR assays for detection of IAV in swine, and (3) an rRT-PCR assay for
      subtyping swine IAV. RNA extraction procedures include a magnetic bead method
      optimized for extraction from nasal swabs and tissue homogenates and a magnetic
      bead method optimized for extraction from oral fluids. Two rRT-PCR assays for
      detection of swine IAV include a USDA-validated IAV rRT-PCR targeting the matrix
      gene and the USDA-licensed VetMAXTM-Gold Swine Influenza Virus Detection rRT-PCR
      kit (Life Technologies) targeting the nucleoprotein and matrix genes. The swine
      IAV subtyping assays described here are multiplex SIV HA (H1 and H3) and NA (N1
      and N2) subtyping rRT-PCR reagents from Life Technologies. 

PMID- 24899438
TI  - Hemagglutinin inhibition assay with swine sera.
AB  - Hemagglutination is based on the ability of viruses such as influenza A virus to
      agglutinate red blood cells (RBCs) of specific animal species by formation of
      cross-linking lattices between RBCs. Antibodies that have the ability to inhibit
      the hemagglutination property of influenza A viruses are correlated with
      protection from infection. The hemagglutination inhibition (HI) test is a
      serological assay that measures the titer of specific antibodies in the sera and
      is the most common serological assay used to detect anti-influenza antibodies in
      swine sera. 

PMID- 24899439
TI  - Enzyme-linked immunosorbent assay for detection of serum or mucosal isotype
      specific IgG and IgA whole-virus antibody to influenza A virus in swine.
AB  - Enzyme-linked immunosorbent assays can be used to detect isotype-specific anti
      influenza antibodies in biological samples to characterize the porcine immune
      response to influenza A virus. The isotype antibody assay is based on an indirect
      ELISA using whole influenza virus as antigen and detection antibodies directed
      against porcine IgG and IgA. Samples such as serum, nasal wash, and
      bronchoalveolar lavage fluid allow for evaluation of systemic, upper, and lower
      respiratory tract mucosal antibody responses, respectively. The isotype ELISA
      assay is performed in a 96-well format using anti-swine detection antibodies
      conjugated to an enzyme that catalyze a color change reaction. The optical
      density of the sample is measured using an automated plate reader. The assay is
      useful to characterize the IgG or the IgA response to challenge or vaccination
      against specific influenza virus isolates in different compartments of the immune
      system. 

PMID- 24899440
TI  - Serum virus neutralization assay for detection and quantitation of serum
      neutralizing antibodies to influenza A virus in swine.
AB  - The serum virus neutralization (SVN) assay is a serological test to detect the
      presence and magnitude of functional systemic antibodies that prevent infectivity
      of a virus. The SVN assay is a highly sensitive and specific test that may be
      applied to influenza A viruses in swine to measure the titer of neutralizing
      antibodies post-infection or after vaccination. Conventional SVN methods
      performed in vitro are based on inhibition of virus infectivity in cell culture
      in the presence of neutralizing antibodies. Titer determination may be based on
      the presence or the absence of cytopathic effect or the evidence of viral
      infection using an immunoreactive technique. The SVN assay is relatively
      inexpensive using standard laboratory equipment although it requires cell
      culture, more time and labor, and technical skill to conduct the assay compared
      to other serological methods. The SVN test is useful to evaluate the level of
      serological cross-reactivity between vaccine antisera and variant influenza
      viruses that may correlate with cross-protection in the host. 

PMID- 24899441
TI  - Microneutralization assay for swine influenza virus in swine serum.
AB  - The microneutralization (MN) assay is a modification of the serum virus
      neutralization assay and is a serological test to detect the presence of
      functional systemic antibodies that prevent infectivity of virus. When infectious
      virus is mixed with serum antibody, the virus infectivity can be "neutralized" if
      the antibodies bind to blocking epitopes on the virus. The neutralization effect
      can be demonstrated by inoculation of susceptible cells or organisms with the
      antibody-virus mixture, such as cells in culture, embryonated eggs, or
      susceptible hosts. The results of the MN assay described here are measured based
      on cell culture in a microtiter plate format and a color change detected by an
      automated plate reader. The test is performed with a constant amount of virus and
      serial dilutions of serum samples to an end point where virus neutralization is
      no longer detected. The neutralizing antibody titer is thus the reciprocal number
      of the last dilution of serum with neutralizing activity. The MN assay can be
      used to detect antibody from pigs with natural exposure or vaccination and can
      potentially be used to predict cross-protection between strains of influenza A
      virus. 

PMID- 24899442
TI  - Analyzing swine sera for functional antibody titers against influenza A
      neuraminidase proteins using an enzyme-linked lectin assay (ELLA).
AB  - Neuraminidase (NA) is an envelope glycoprotein of influenza viruses, including
      swine-lineage influenza A viruses. NA possesses sialidase activity, which is
      functionally important at multiple points in viral replication, counter-balancing
      the sialic acid receptor binding activity of the hemagglutinin (HA), the other
      major envelope glycoprotein. The NA proteins of influenza A viruses have been
      classified into nine serological subtypes, and they undergo antigenic drift
      variation similar to that of HA. Antibodies to NA are analyzed much less often
      than antibodies to HA. The conventional assay for NA inhibition (NI) antibody
      titration, established decades ago, is widely considered unwieldy and inefficient
      for routine use. In recent years, a few new formats have been developed which
      still measure inhibition of NA enzymatic function, but more efficiently and with
      less chemical waste produced. Described here is the enzyme-linked lectin assay
      (ELLA), which is performed in 96-well plates and analyzed on a spectrophotometric
      plate reader. An important factor in adoption of the ELLA technique for animal
      studies, such as swine, is the choice of NA antigen, which may be purified
      protein or whole virus containing an antigenically irrelevant HA protein. This NI
      assay, in conjunction with the hemagglutination inhibiting (HI) antibody assay,
      offers a practical way to characterize viral isolates more fully and to quantify
      antibodies induced by infection or vaccination. 

PMID- 24899443
TI  - Antibody secreting cell assay for influenza A virus in swine.
AB  - An ELISPOT assay to enumerate B-cells producing antibodies specific to a given
      antigen, also known as an antibody secreting cell (ASC) assay, was adapted to
      detect B-cells specific for influenza A virus (IAV). The assay is performed ex
      vivo and enumerates ASC at a single cell level. A simple ASC detection method is
      based on a solid phase immunoenzymatic principle. The ELISPOT plate is coated
      with IAV prior to incubation with cell samples. The spot-forming cells are
      detected by enzyme labeled antibodies directed to the swine immunoglobulin (Ig)
      class of interest and visualized with the addition of substrate. 

PMID- 24899444
TI  - In vivo models for pathotyping and vaccine efficacy for swine influenza.
AB  - Swine influenza is a disease of the respiratory tract caused by influenza A virus
      (IAV). Experimental inoculation of pigs involves either aerosolization and
      inhalation of virus or the direct introduction of virus into the upper or lower
      respiratory tract. This chapter covers methods for experimental IAV infection of
      pigs and collection of specific samples to study the pathogenesis of swine
      influenza and vaccine efficacy. 

PMID- 24899445
TI  - A brief introduction to equine influenza and equine influenza viruses.
AB  - Equine influenza virus (EIV) is a common respiratory pathogen of horses and other
      equids in most parts of the world. EIV are Type A influenza viruses and two
      subtypes are known: H3N8 and H7N7. Both are believed to have evolved from avian
      influenza virus ancestors. The H3N8 subtype circulates widely, but the H7N7
      subtype is thought to be extinct. The clinical disease in horses, caused by
      either subtype, is an upper respiratory infection of varying severity depending
      upon the immune status of the individual animal. It is not normally life
      threatening in itself except in very young foals; however it predisposes infected
      equids to secondary infections capable of producing life-threatening pneumonias.
      Vaccines are available and widely used in some horse populations, but their
      effectiveness is limited by antigenic drift and other factors, and vaccinated
      animals with subclinical infections have been responsible for introduction of EIV
      into susceptible populations. EIV has spread into canines. 

PMID- 24899446
TI  - Equine influenza diagnosis: sample collection and transport.
AB  - In horses, presumptive diagnosis of equine influenza is commonly made on the
      basis of clinical signs. This alone is insufficient for confirmation of equine
      influenza, because other equine infectious respiratory diseases can in some
      degree have similar clinical presentations. Surveillance and control of equine
      influenza also necessitate detection of subclinical cases. Effective diagnosis of
      equine influenza virus infection is critically dependent on obtaining adequate
      specimens of virus-containing respiratory secretions for testing. These specimens
      are also valuable as sources for isolation of virus strains for antigenic
      characterization and potential inclusion in vaccines. Both nasal swabs and
      nasopharyngeal swabs are employed in horses. These differ little in their
      invasiveness, but nasopharyngeal swabs typically yield more virus than nasal
      swabs and are superior diagnostic specimens. Methods for obtaining nasopharyngeal
      swab specimens are described. 

PMID- 24899448
TI  - Type A influenza virus detection from horses by real-time RT-PCR and insulated
      isothermal RT-PCR.
AB  - Equine influenza (EI) is a highly contagious disease of horses caused by the
      equine influenza virus (EIV) H3N8 subtype. EI is the most important respiratory
      virus infection of horses and can disrupt major equestrian events and cause
      significant economic losses to the equine industry worldwide. Influenza H3N8
      virus spreads rapidly in susceptible horses and can result in very high morbidity
      within 24-48 h after exposure to the virus. Therefore, rapid and accurate
      diagnosis of EI is critical for implementation of prevention and control measures
      to avoid the spread of EIV and to reduce the economic impact of the disease. The
      probe-based real-time reverse transcriptase polymerase chain reaction (rRT-PCR)
      assays targeting various EIV genes are reported to be highly sensitive and
      specific compared to the Directigen Flu A((r)) test and virus isolation in
      embryonated hens' eggs. Recently, a TaqMan((r)) probe-based insulated isothermal
      RT-PCR (iiRT-PCR) assay for the detection of EIV H3N8 subtype has been described.
      These molecular based diagnostic assays provide a fast and reliable means of EIV
      detection and disease surveillance. 

PMID- 24899447
TI  - RNA extraction from equine samples for equine influenza virus.
AB  - The primary goals of this chapter are to discuss common viral RNA isolation and
      purification methods that are routinely used by various diagnostic laboratories,
      to highlight the advantages and drawbacks of each method, and to identify the
      most suitable and reliable method to increase the sensitivity and specificity of
      RT-PCR assays for the detection of equine influenza virus (EIV) in clinical
      specimens. Our experiences and review of literature show that magnetic bead-based
      nucleic extraction methods (manual and automatic) work well for isolation and
      purification of EIV RNA from nasal swab specimens. Furthermore, most of the
      information presented in this chapter could be directly applicable to isolation
      and purification of nucleic acids (both DNA and RNA) from other equine clinical
      samples. 

PMID- 24899449
TI  - Equine influenza culture methods.
AB  - Equine influenza viruses are cultured in embryonated hen eggs, or in mammalian
      cells, generally Madin-Darby canine kidney (MDCK) cells, using methods much the
      same as for other influenza A viruses. Mutations associated with host adaptation
      occur in both eggs and MDCK cells, but the latter show greater heterogeneity and
      eggs are the generally preferred host. Both equine-1 H7N7 and equine-2 H3N8
      viruses replicate efficiently in 11-day-old eggs, but we find that equine-1
      viruses kill the embryos whereas equine-2 viruses do not. 

PMID- 24899450
TI  - Equine influenza serological methods.
AB  - Serologic tests for equine influenza virus (EIV) antibodies are used for many
      purposes, including retrospective diagnosis, subtyping of virus isolates,
      antigenic comparison of different virus strains, and measurement of immune
      responses to EIV vaccines. The hemagglutination-inhibition (HI), single radial
      hemolysis (SRH), and serum micro-neutralization tests are the most widely used
      for these purposes and are described here. The presence of inhibitors of
      hemagglutination in equine serum complicates interpretation of HI assay results,
      and there are alternative protocols (receptor-destroying enzyme, periodate,
      trypsin-periodate) for their removal. With the EIV H3N8 strains in particular,
      equine antibody titers may be magnified by pretreating the HI test antigen with
      Tween-80 and ether. The SRH assay offers stronger correlations between serum
      antibody titers and protection from disease. Other tests are sometimes used for
      specialized purposes such as the neuraminidase-inhibition assay for subtyping, or
      ELISA for measuring different specific antibody isotypes, and are not described
      here. 

PMID- 24899451
TI  - Values and pragmatism.

PMID- 24899453
TI  - Expanding access to Spanish-speaking communities: a critical partnership.

PMID- 24899455
TI  - Increasing children's physical activity during school recess periods.
AB  - OBJECTIVES: We examined whether schools' participation in the Recess Enhancement
      Program (REP) in the spring of 2011 was associated with higher rates of
      children's vigorous physical activity. METHODS: In REP, a coach guides children
      through age-appropriate games aimed at increasing their physical activity. During
      recess at 25 New York City public elementary schools (15 REP, 10 non-REP),
      researchers visually scanned predetermined areas (n = 1339 scans), recording the
      number of sedentary, walking, and very active children. RESULTS: Multivariate
      statistical analysis found that participation in REP was a significant predictor
      (P = .027) of the rate of vigorous physical activity (percentage very active in
      scan area) whose least-squares means were 41% in REP schools and 27% in non-REP
      schools. A significantly higher rate in REP schools persisted when the coach was
      not in the scan area, suggesting a change in the recess culture of REP schools.
      CONCLUSIONS: The rate of vigorous physical activity in REP schools was 14
      percentage points, or 52%, higher than the rate in non-REP schools. This low-cost
      intervention might be a valuable addition to the tools for combating childhood
      obesity and worth replicating elsewhere.

PMID- 24899457
TI  - Eliminating tuberculosis one neighborhood at a time.
AB  - OBJECTIVES: We evaluated a strategy for preventing tuberculosis (TB) in
      communities most affected by it. METHODS: In 1996, we mapped reported TB cases
      (1985-1995) and positive tuberculin skin test (TST) reactors (1993-1995) in Smith
      County, Texas. We delineated the 2 largest, densest clusters, identifying 2
      highest-incidence neighborhoods (180 square blocks, 3153 residents). After
      extensive community preparation, trained health care workers went door-to-door
      offering TST to all residents unless contraindicated. TST-positive individuals
      were escorted to a mobile clinic for radiography, clinical evaluation, and
      isoniazid preventive treatment (IPT) as indicated. To assess long-term impact, we
      mapped all TB cases in Smith County during the equivalent time period after the
      project. RESULTS: Of 2258 eligible individuals, 1291 (57.1%) were tested, 229
      (17.7%) were TST positive, and 147 were treated. From 1996 to 2006, there were no
      TB cases in either project neighborhood, in contrast with the preintervention
      decade and the continued occurrence of TB in the rest of Smith County.
      CONCLUSIONS: Targeting high-incidence neighborhoods for active, community-based
      screening and IPT may hasten TB elimination in the United States.

PMID- 24899461
TI  - Ti(OiPr)4/nBuLi: an attractive reagent system for [2+2+2] cyclotrimerisation
      reactions.
AB  - A convenient method for the [2+2+2] cyclotrimerisation of alkynes using
      Ti(OiPr)4/nBuLi is presented. Homotrimerisation of arylacetylenes proceeds within
      minutes with excellent regioselectivity. Moreover, the intermolecular
      construction of ABB heterotrimers can be achieved selectively from two different
      alkynes with similar electronic properties. The method is also suitable for the
      synthesis of pyridines. 

PMID- 24899459
TI  - Immigrant generation and diabetes risk among Mexican Americans: the Sacramento
      area Latino study on aging.
AB  - OBJECTIVES: We examined whether acculturation and immigrant generation, a marker
      for assimilation, are associated with diabetes risk in an aging Mexican-origin
      population. METHODS: We analyzed data on 1789 adults aged 60 to 101 years from
      the Sacramento Area Latino Study on Aging. We ascertained type 2 diabetes on the
      basis of diabetic medication use, self-report of physician diagnosis, or a
      fasting glucose of 126 milligrams/deciliter or greater. Logistic regression
      modeled prevalent diabetes. RESULTS: Adjusting for age and gender, we observed
      significant but divergent associations between immigrant generation,
      acculturation, and diabetes risk. Relative to first-generation adults, second
      generation adults had an odds ratio (OR) of 1.8 (95% confidence interval [CI] =
      1.4, 2.4) and third-generation adults had an OR of 2.1 (95% CI = 1.4, 3.1) of
      having diabetes. Greater US acculturation, however, was associated with a
      slightly decreased diabetes rate. In the full model adjusting for socioeconomic
      and lifestyle factors, the association between generation (but not acculturation)
      and diabetes remained significant. CONCLUSIONS: Our study lends support to the
      previously contested notion that assimilation is associated with an increased
      diabetes risk in Mexican immigrants. Researchers should examine the presence of a
      causal link between assimilation and health more closely.

PMID- 24899460
TI  - Age-related changes in mRNA levels of hepatic transporters, cytochrome P450 and
      UDP-glucuronosyltransferase in female rats.
AB  - Hepatic transporters and metabolic enzymes affect drug pharmacokinetics. Limited
      information exists on the alteration in mRNA levels of hepatic transporters and
      metabolic enzymes with aging. We examined the effects of aging on the mRNA levels
      of representative hepatic drug transporters and metabolic enzymes by analyzing
      their levels in 10-, 30- and 50-week-old male and female rats. Levels of mRNA of
      drug transporters including multidrug resistance protein (Mdr)1a, multidrug
      resistance-associated protein (Mrp)2, breast cancer resistance protein (Bcrp) and
      organic anion-transporting polypeptide (Oatp)1a1, and the metabolic enzymes
      cytochrome P450 (CYP)3A1, CYP3A2 and UDP-glucuronosyltransferase (UGT)1A1 were
      analyzed using real-time reverse transcriptase polymerase chain reaction. The
      mRNA levels of transporters in male rats did not decrease with age, while the
      mRNA levels of Bcrp and Oatp1a1 in female rats decreased with age. The mRNA
      levels of CYP3A1 and CYP3A2 in male rats were higher than those in female rats.
      The mRNA levels of metabolic enzymes decreased with age in female but not male
      rats. In particular, the mRNA levels of UGT1A1 in 10-week-old female rats were
      higher than those in male rats. mRNA expression of hepatic transporters and
      metabolic enzymes are more susceptible to aging in female than male rats. The age
      related decreases in the mRNA levels of Bcrp, Oatp1a1, CYP3A1 and CYP3A2 in
      female rats may affect the metabolism and transport of substrates. This study
      showed that aging affected the mRNA expression of hepatic transporters and
      metabolic enzymes in rats. 

PMID- 24899462
TI  - Laparoscopic Extirpation of the Medial Iliac Lymph Nodes in Normal Dogs.
AB  - OBJECTIVE: To describe a surgical technique for laparoscopic medial iliac lymph
      node (MILN) extirpation, and to describe the quality of biopsy specimens
      obtained. DESIGN: Experimental study. ANIMALS: Purpose-bred male hound-mix
      research dogs (n = 8). METHODS: Dogs were randomized to groups of left or right
      sided laparoscopic surgical approaches. Three transperitoneal portals were
      established with the dogs in lateral recumbency, and ipsilateral MILN dissection
      was achieved under CO2 pneumoperitoneum using a vessel-sealing device. RESULTS:
      MILN ipsilateral to the approach were successfully identified and removed
      laparoscopically in 8 dogs. Observed complications included mild to moderate
      hemorrhage that was controlled laparoscopically in 4 dogs, and tearing of the
      MILN capsule during retraction and dissection in 3 dogs. No other major
      complications occurred and all dogs recovered uneventfully. Areas of either minor
      peripheral (9/9) or central (4/9) pinch artifact affected a median percentage of
      5% of surface area (range, 5-30%) of bisected lymph nodes. CONCLUSIONS:
      Laparoscopic MILN extirpation is feasible in dogs with normal MILN and may serve
      as a minimally invasive approach for excisional biopsy in the diagnostic staging
      of canine onocologic patients with normal-sized MILN. This lateral laparoscopic
      approach allows dissection of the ipsilateral MILN but precludes removal of the
      contralateral MILN. Minimal handling of the lymph node during dissection and
      removal is required to reduce the risk of capsular tear, or introduction of
      possible histologic artifact by tissue crush that may impact diagnosis.

PMID- 24899463
TI  - Intraoperative sentinel lymph node assessment in breast cancer: a comparison of
      rapid diagnostic method based on CK19 mRNA expression and imprint cytology.
AB  - BACKGROUND: Sentinel lymph node biopsy in breast cancer is a routine technique
      for staging the axilla. The two most common methods of intraoperative
      histopathological assessment, imprint cytology and frozen section, are hampered
      by poor sensitivity and lack standardized methodology. The one-step nuclei acid
      amplification (OSNA) assay is a rapid quantification of cytokeratin 19 mRNA. This
      prospective study compared an existing intraoperative imprint cytology protocol
      with the OSNA system. METHODS: Of the 110 prospectively recruited patients, 98
      met the inclusion criteria with a total of 170 lymph nodes. Intraoperative
      sentinel nodes were serially sectioned and imprints made of each cut surface for
      cytological assessment. Alternate slices were submitted for OSNA while the
      remaining slices were for final histopathological evaluation with six hematoxylin
      and eosin levels and one AE1/AE3 immunoperoxidase stain of each slice. RESULTS:
      On histopathological analysis, 24.5% of patients (16.5% of nodes) had sentinel
      node metastases and 3.1% (2.4%) had isolated tumour cells. With isolated tumour
      cells cases taken as negative, the sensitivity of imprint cytology and OSNA
      compared with histopathology were 66.7% on patient basis (71.4% on per-node
      basis) and 95.8% (89.3%), respectively. One of 22 patients with macrometastases
      and two of three micrometastases were designated negative while five false
      positive nodes were identified with OSNA, likely due to tissue allocation bias.
      CONCLUSION: The OSNA assay is highly sensitive in comparison with imprint
      cytology and may be used effectively in the intraoperative setting. Clinical
      follow-up studies are warranted to further assess its use in routine practice.

PMID- 24899465
TI  - Ftx is dispensable for imprinted X-chromosome inactivation in preimplantation
      mouse embryos.
AB  - X-chromosome inactivation (XCI) equalizes gene expression between the sexes by
      inactivating one of the two X chromosomes in female mammals. Xist has been
      considered as a major cis-acting factor that inactivates the paternally derived X
      chromosome (Xp) in preimplantation mouse embryos (imprinted XCI). Ftx has been
      proposed as a positive regulator of Xist. However, the physiological role of Ftx
      in female animals has never been studied. We recently reported that Ftx is
      located in the cis-acting regulatory region of the imprinted XCI and expressed
      from the inactive Xp, suggesting a role in the imprinted XCI mechanism. Here we
      examined the effects on imprinted XCI using targeted deletion of Ftx. Disruption
      of Ftx did not affect the survival of female embryos or expression of Xist and
      other X-linked genes in the preimplantation female embryos. Our results indicate
      that Ftx is dispensable for imprinted XCI in preimplantation embryos. 

PMID- 24899464
TI  - Roux-en-Y gastric bypass surgery or lifestyle with intensive medical management
      in patients with type 2 diabetes: feasibility and 1-year results of a randomized
      clinical trial.
AB  - IMPORTANCE: Emerging data support bariatric surgery as a therapeutic strategy for
      management of type 2 diabetes mellitus. OBJECTIVE: To test the feasibility of
      methods to conduct a larger multisite trial to determine the long-term effect of
      Roux-en-Y gastric bypass (RYGB) surgery compared with an intensive diabetes
      medical and weight management (Weight Achievement and Intensive Treatment [Why
      WAIT]) program for type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A 1-year
      pragmatic randomized clinical trial was conducted in an academic medical
      institution. Participants included persons aged 21 to 65 years with type 2
      diabetes diagnosed more than 1 year before the study; their body mass index was
      30 to 42 (calculated as weight in kilograms divided by height in meters squared)
      and hemoglobin A1c (HbA1c) was greater than or equal to 6.5%. All participants
      were receiving antihyperglycemic medications. INTERVENTIONS: RYGB (n = 19) or Why
      WAIT (n = 19) including 12 weekly multidisciplinary group lifestyle, medical, and
      educational sessions with monthly follow-up thereafter. MAIN OUTCOMES AND
      MEASURES: Proportion of patients with fasting plasma glucose levels less than 126
      mg/dL and HbA1c less than 6.5%, measures of cardiometabolic health, and patient
      reported outcomes. RESULTS: At 1 year, the proportion of patients achieving HbA1c
      below 6.5% and fasting glucose below 126 mg/dL was higher following RYGB than Why
      WAIT (58% vs 16%, respectively; P = .03). Other outcomes, including HbA1c,
      weight, waist circumference, fat mass, lean mass, blood pressure, and
      triglyceride levels, decreased and high-density lipoprotein cholesterol increased
      more after RYGB compared with Why WAIT. Improvement in cardiovascular risk scores
      was greater in the surgical group. At baseline the participants exhibited
      moderately low self-reported quality-of-life scores reflected by Short Form-36
      total, physical health, and mental health, as well as high Impact of Weight on
      Quality of Life-Lite and Problem Areas in Diabetes health status scores. At 1
      year, improvements in Short Form-36 physical and mental health scores and Problem
      Areas in Diabetes scores did not differ significantly between groups. The Impact
      of Weight on Quality of Life-Lite score improved more with RYGB and correlated
      with greater weight loss compared with Why WAIT. CONCLUSIONS AND RELEVANCE: In
      obese patients with type 2 diabetes, RYGB produces greater weight loss and
      sustained improvements in HbA1c and cardiometabolic risk factors compared with
      medical management, with emergent differences over 1 year. Both treatments
      improve general quality-of-life measures, but RYGB provides greater improvement
      in the effect of weight on quality of life. These differences may help inform
      therapeutic decisions for diabetes and weight loss strategies in obese patients
      with type 2 diabetes until larger randomized trials are performed. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01073020.

PMID- 24899466
TI  - Cortical representations of confidence in a visual perceptual decision.
AB  - To date the exact neuronal implementation of decision confidence has been subject
      to little research. Here we explore electroencephalographic correlates of human
      choice certainty in a visual motion discrimination task for either spatial
      attention or motor effector cue instructions. We demonstrate electrophysiological
      correlates of choice certainty that evolve as early as 300 ms after stimulus
      onset and resemble the primary visual motion representations in early visual
      cortex. These correlates do not emerge unless or until the subject unambiguously
      knows which of the competing visual stimuli is actually relevant to behaviour.
      They extend beyond stimulus presentation up to the motor response but are
      independent of the motor effector. Our findings suggest that perceptual
      confidence evolves in parallel with representations of stimulus properties and is
      dedicated to one specific aspect of the visual world. Its electroencephalographic
      correlates can be disentangled from representations of sensory evidence,
      objective discrimination performance and overt motor behaviour.

PMID- 24899467
TI  - In vitro comparison of output fluid temperatures for room temperature and
      prewarmed fluids.
AB  - OBJECTIVE: To determine if prewarmed intravenous fluids produce superior fluid
      output temperatures compared with room temperature fluids at common anaesthetic
      fluid rates for small animal patients. METHODS: A prospective, randomised, in
      vitro fluid line test-vein study was performed. Nine flow rates were analysed
      (10, 20, 60, 100, 140, 180, 220, 260 and 300 mL/hour) for room temperature fluids
      (21 degrees C) and for five prewarmed fluids (40, 45, 50, 55 and 60 degrees C).
      RESULTS: For each flow rate tested, room temperature fluids never exceeded 25
      degrees C at any time point for each trial (range 18 to 25 degrees C). For each
      flow rate tested, prewarmed fluids never exceeded 25 . 5 degrees C at any time
      point for each trial (range 18 to 25 . 5 degrees C). The mean output fluid
      temperature of prewarmed fluids was significantly warmer than room temperature
      fluids only at 300 mL/hour for 40 degrees C (P = 0 . 0012), 45 degrees C (P = 0 .
      004), 50 degrees C (P = 0 . 0002), 55 degrees C (P = 0 . 0001) and 60 degrees C
      (P < 0 . 0001). CLINICAL SIGNIFICANCE: There was no thermodynamic benefit to
      utilising prewarmed intravenous fluids (up to 60 degrees C) compared with room
      temperature intravenous fluids at common anaesthetic fluid rates for small
      animals.

PMID- 24899468
TI  - 2-methoxyestradiol plasma levels are associated with clinical severity indices
      and biomarkers of preeclampsia.
AB  - We investigated whether clinical severity indices and biomarkers for preeclampsia
      (PE) are associated with low plasmatic 2-methoxyestradiol (2ME) in the third
      trimester of gestation. Blood was collected from 53 women with PE and 73 control
      pregnant women before parturition. The concentration of 2ME was significantly
      higher in controls than in patients with PE (2906.43 +/- 200.69 pg/mL vs 1818.41
      +/- 189.25 pg/mL). The risk of PE decreased as 2ME levels increased. The 2ME
      values were negatively correlated with systolic peak arterial pressure and
      proteinuria in PE. Additionally, those women with PE with lower 2ME had a more
      serious clinical situation and needed a more aggressive therapy. Finally, 2ME
      levels (in patients with PE and total population) were significantly correlated
      with concentrations of soluble fms-like tyrosine kinase 1 and placental growth
      factor . Summarizing, patients with PE had lower 2ME levels that were correlated
      with different clinical indices and biomarkers of severity, indicating that 2ME
      could be taken into account for the clinical management of this syndrome. 

PMID- 24899471
TI  - Molecular signature in human cumulus cells related to embryonic developmental
      potential.
AB  - Identification of criteria for embryo quality is required to improve the clinical
      outcome of in vitro fertilization. The aim of this study was to determine the
      gene expression profile of cumulus cells (CC) surrounding the oocyte as
      biomarkers for embryonic developmental potential. CCs from single oocytes were
      analysed using DNA microarrays. Gene expression profiles of CC surrounding the
      oocyte associated with good embryonic quality were analyzed. We observed that CCs
      issued from oocytes that developed into embryos with a good morphology had
      significantly different gene expression profile from those with bad morphology.
      These results were confirmed by quantitative RT-PCR. The gene expression
      profiling of human CC correlates with embryo potential. Our findings suggest anon
      invasive approach, offering a new potential strategy for competent embryo
      selection. 

PMID- 24899470
TI  - Systemic and placental leptin and its receptors in pregnancies associated with
      obesity.
AB  - This study aimed to gain new insights into both systemic and placental leptin and
      its receptors, with reference to the maternal prepregnancy body mass index (BMI).
      Thus, 84 women (29 lean, 24 overweight, and 31 obese) were recruited and
      maternal, cord blood, and placental tissues collected prior to term labor. Plasma
      levels were measured by enzyme-linked immunosorbent assay and for placenta,
      immunohistochemistry and messenger RNAs (mRNAs) were quantitated. We confirmed
      that maternal leptin increased linearly as the soluble receptor decreased with
      BMI (P = .001). Fetal leptin increased with maternal BMI (P = .02) and birth
      weight (P = .006) and was higher in female infants (P < .001). Placental mRNA
      levels of leptin and its receptors showed no change in BMI. However, we show a
      significant (P = .043) linear increase in leptin in the placental vascular
      endothelial cells with maternal obesity, while leptin in syncytiotrophoblast
      showed no statistical change. Leptin receptors localized to syncytiotrophoblast
      and intravillous macrophages and were unchanged with BMI. 

PMID- 24899472
TI  - Mid-trimester maternal ADAM12 levels differ according to fetal gender in
      pregnancies complicated by preeclampsia.
AB  - An overrepresentation of adverse pregnancy outcomes has been observed in
      pregnancies associated with a male fetus. We investigated the association between
      fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified
      in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy
      Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In
      contrast to placental growth factor, soluble endoglin, and insulin-like growth
      factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20
      weeks were dependent on fetal gender in pregnancies complicated by preeclampsia,
      for male (n = 73) fetuses the multiples of the median (MoM; interquartile range
      [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0
      1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for
      pregnancies associated with a male fetus (area under receiver-operator curve
      [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus
      (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary
      hypothesis that there is a difference between the genders in response to an
      adverse maternal environment and suggest that an alteration in ADAM12 may reflect
      an altered placental response in pregnancies subsequently complicated by
      preeclampsia. 

PMID- 24899469
TI  - Influenza, immune system, and pregnancy.
AB  - Influenza is a major health problem worldwide. Both seasonal influenza and
      pandemics take a major toll on the health and economy of our country. The present
      review focuses on the virology and complex immunology of this RNA virus in
      general and in relation to pregnancy. The goal is to attempt to explain the
      increased morbidity and mortality seen in infection during pregnancy. We discuss
      elements of innate and adaptive immunity as well as placental cellular responses
      to infection. In addition, we delineate findings in animal models as well as
      human disease. Increased knowledge of maternal and fetal immunologic responses to
      influenza is needed. However, enhanced understanding of nonimmune, pregnancy
      specific factors influencing direct interaction of the virus with host cells is
      also important for the development of more effective prevention and treatment
      options in the future. 

PMID- 24899475
TI  - Angiographic scoring systems in patients with acute myocardial infarction.

PMID- 24899474
TI  - A simple angiographic index to predict adverse clinical outcome associated with
      acute myocardial infarction.
AB  - OBJECTIVES: The major determinant of final infarct size for a given coronary
      occlusion is the size of the myocardial area-at-risk. We propose herein a new
      index 'Relative Importance Index (RII)' to predict area-at-risk in patients with
      anterior myocardial infarction (MI). The aim of the study was to assess the
      predictive value of RII in left ventricle (LV) systolic function reduction and
      its relation to adverse clinical outcome. STUDY DESIGN: One hundred twenty-three
      acute anterior MI patients with their first acute coronary syndrome incident were
      consecutively and prospectively enrolled in to the study. RII was calculated by
      dividing the culprit segment diameter by the sum of diameters of the left
      anterior descending, circumflex, and right coronary arteries at their proximal
      segments. We evaluated the one-month follow-up rates of major clinical endpoints,
      which were defined as death, non-fatal MI, stroke, and new congestive heart
      failure (CHF). RESULTS: RII was significantly and negatively correlated with left
      ventricular ejection fraction (LVEF) (r=-0.65, p<0.001). Likewise, RII was
      significantly correlated with 72 hour troponin I (TnI) (r=0.48, p<0.001).
      Patients were dichotomized according to the median value of RII (median RII:
      0.30). Supra-median RII was associated with lower EF (32.8+/-8.6 vs. 42.8+/-9.4,
      p<0.001) and higher incidence of composite major adverse cardiac events (33.9%
      vs. 13.1%, p=0.01). The mortality, non-fatal MI and new CHF rates in the supra
      median RII group trended higher but they did not reach statistical significance.
      An RII >0.30 had an 88% sensitivity and 60% specificity (ROC area: 0.82, p<0.001,
      CI: 0.73-0.90) for predicting severe LV dysfunction (LVEF<30%). CONCLUSION: A
      simple index derived from coronary angiography at the time of primary
      percutaneous coronary intervention can predict LV systolic function loss and
      adverse clinical outcome in patients with acute anterior MI.

PMID- 24899473
TI  - Increased progesterone production in cumulus-oocyte complexes of female mice
      sired by males with the Y-chromosome long arm deletion and its potential
      influence on fertilization efficiency.
AB  - It was revealed previously that B10.BR(Y(del)) females sired by males with the Y
      chromosome long arm deletion differ from genetically identical B10.BR females
      sired by males with the intact Y chromosome. This is interpreted as a result of
      different epigenetic information which females of both groups inherit from their
      fathers. In the following study, we show that cumulus-oocyte complexes ovulated
      by B10.BR(Y(del)) females synthesize increased amounts of progesterone, which is
      important sperm stimulator. Because their extracellular matrix is excessively
      firm, the increased progesterone secretion belongs presumably to factors that
      compensate this feature enabling unchanged fertilization ratios. Described
      compensatory mechanism can act only on sperm of high quality, presenting proper
      receptors. Indeed, low proportion of sperm of Y(del) males that poorly fertilize
      B10.BR(Y(del)) oocytes demonstrates positive staining of membrane progesterone
      receptors. This proportion is significantly higher for sperm of control males
      that fertilize B10.BR(Y(del)) and B10.BR oocytes with the same efficiency. 

PMID- 24899476
TI  - [Prevalence and clinical features of microfistulas between the coronary artery
      and left ventricle: single-center experience].
AB  - OBJECTIVES: Coronary artery fistula is an infrequent malformation, and the
      prevalence was reported as approximately 0.1-0.4% in previous studies. However,
      the number of studies about microfistulas from coronary arteries to the left
      ventricle is inadequate, especially in the Turkish population. The purpose of
      this study was to evaluate the prevalence and clinical features of microfistulas
      in subjects undergoing coronary angiography for the assessment of coronary artery
      disease. STUDY DESIGN: In this retrospective study, we researched the cardiac
      catheterization laboratory database between January 2008 and July 2013. The
      presence of microfistulas was established according to the following criteria: 1)
      direct filling of the heart cavity during selective coronary injection without
      interposing "capillary" phase or venous filling, and 2) visualization of small
      vessels interposed between the epicardial coronary vessels and the heart cavity
      and emptying into the heart. RESULTS: Microfistulas were found in 12 (0.11%) of
      the 11403 coronary angiographies. There were 7 (58.3%) female patients (mean age,
      70.2+/-10.8 years), and contemporary severe coronary artery stenosis was noted in
      2 (16.7%) patients. Chest pain was the most frequently encountered complaint,
      followed by dyspnea. Microfistulas originated from the left anterior descending
      artery (100%), circumflex artery (66.7%), and right coronary artery (58.3%). In
      addition, multiple microfistulas were seen in 6 (50%) patients, bilateral
      microfistulas in 3 (25%) patients and unilateral microfistula in 3 (25%)
      patients, and all of them terminated in the left ventricle. CONCLUSION: Our study
      found an overall incidence of microfistulas of 0.11%. Microfistula is a rare
      cardiac anomaly that sometimes causes cardiac symptoms; otherwise, it is detected
      during routine coronary angiography.

PMID- 24899477
TI  - Efficacy and safety of valsartan/amlodipine single-pill combination in patients
      with essential hypertension (PEAK LOW).
AB  - OBJECTIVES: This study evaluated the efficacy as well as the safety and
      tolerability profile of low-dose valsartan/amlodipine (Val/Amlo) single-pill
      combination (SPC) (160/5 mg) in patients with essential hypertension in Turkey.
      STUDY DESIGN: Adult patients with essential hypertension [systolic blood pressure
      (SBP)>140 mmHg and/or diastolic blood pressure (DBP)>90 mmHg], who were on low
      dose Val/Amlo (160/5 mg) SPC before enrollment and gave informed consent, were
      accepted for this multi-centric observational study performed at 30 sites. The
      absolute changes in SBP and DBP from baseline were the primary efficacy outcomes.
      Safety assessments consisted of recording all adverse events. RESULTS: Of 381
      patients enrolled, 327 completed the study; 39% were females. The mean age was
      57.3+/-11.8 years. Median duration of hypertension was 38 months. Both SBP and
      DBP values showed reductions from 162.6+/-16.6 mmHg and 94.0+/-13.2 mmHg to
      137.6+/-14.2 mmHg and 81.9+/-9.0 mmHg at 4th week and to 131.6+/-11.5 mmHg and
      79.7+/-7.6 mmHg at 12th week, respectively. The control and response rates at the
      end of the study were 82.0% and 92.6%, respectively. Twelve patients (3.2%)
      experienced a total of 12 adverse events; there were no serious adverse events.
      The most common adverse event was edema (1.3%). Patient compliance was
      approximately 99%. CONCLUSION: Low-dose (160/5 mg) Val/Amlo SPC is efficacous and
      has a good tolerability and safety profile for the management of essential
      hypertension in Turkey.

PMID- 24899478
TI  - Comparison of gated myocardial perfusion SPECT, echocardiography and equilibrium
      radionuclide ventriculography in the evaluation of left ventricle contractility.
AB  - OBJECTIVES: In this study, we investigated the reliability of gated myocardial
      perfusion single-photon emission computerized tomography (GSPECT) for the
      evaluation of left ventricle (LV) function. We compared left ventricle ejection
      fraction (LVEF) calculated with GSPECT with the values derived from planar
      equilibrium-gated radionuclide ventriculography (ERVG) and echocardiography
      (ECHO). STUDY DESIGN: Forty-eight patients with suspected coronary artery disease
      (CAD), who were referred for evaluation of myocardial perfusion and LV function
      and underwent two-day 99mTc-MIBI protocol GSPECT and ERVG, were examined
      retrospectively. LVEF was calculated with GSPECT Myometrix software, and wall
      motion and thickness were calculated with QGS analysis program. In the ERVG
      study, LVEF values were calculated using left anterior oblique images. In the
      GSPECT and ERVG study, wall motion was evaluated visually and scored. LVEF values
      and wall motion data measured with ECHO were noted. RESULTS: For all cases, there
      was a significant correlation between LVEF values calculated by GSPECT and ERVG.
      Numerical LVEF values of 30 patients measured with ECHO showed no significant
      difference from the values measured with GSPECT. When 240 segments obtained from
      48 patients were examined, the correlation between GSPECT and ERVG was 77.5% and
      between GSPECT and ECHO was 75.4% by visual wall motion analysis. Quantitatively
      calculated wall motion and thickness scores of segments visually defined as
      normokinetic were significantly higher than segments visually defined as having
      contraction defect. CONCLUSION: GSPECT can be used safely in clinical practice
      for the evaluation of LV function. Quantitatively calculated wall motion and
      thickness scores are promising methods to verify the visual evaluation.

PMID- 24899479
TI  - [Relation between epicardial adipose tissue thickness and blood pressure levels
      in prehypertension].
AB  - OBJECTIVES: Increased epicardial adipose tissue (EAT) thickness is a risk factor
      for cardiovascular diseases. Previous studies have demonstrated that EAT
      thickness is increased in patients with hypertension compared with normotensive
      individuals. In the current study, we aimed to evaluate whether
      echocardiographically measured EAT thickness differs among patients with
      normotension, prehypertension, hypertension, and the relation between EAT
      thickness and blood pressure levels in prehypertensives. STUDY DESIGN: Patients
      with prehypertension (n=50) and hypertension (n=50) and normotensive healthy
      subjects (n=50) according to the American Hypertension Guidelines (Joint National
      Committee 7) were enrolled in the study. All participants underwent transthoracic
      echocardiographic examination. EAT thickness was measured from the parasternal
      long-axis view at end-systole. RESULTS: Compared with normotensives, EAT
      thickness was significantly increased in subjects with prehypertension and
      hypertension (4.1+/-1.1 mm, 5.4+/-1.3 mm and 6.6+/-1.5 mm, respectively,
      p<0.001). After adjustment for confounding factors like age, gender, high-density
      lipoprotein, waist circumference, and body mass index, EAT thickness in the
      normotensive, prehypertensive and hypertensive groups was measured as 4.3+/-1.2
      mm, 5.3+/-1.2 mm and 6.4+/-1.4 mm, respectively (p=0.001). In the prehypertensive
      group, multivariable linear regression analysis showed that EAT thickness was
      positively correlated with both systolic (r=0.305, p=0.001) and diastolic
      (r=0.297, p=0.001) blood pressures, independent of other risk factors.
      CONCLUSION: In addition to hypertensive subjects, echocardiographically measured
      EAT thickness is increased in prehypertensive patients when compared with
      normotensive subjects, independent of other factors. Additionally, increased EAT
      thickness is significantly correlated with systolic and diastolic blood pressure
      levels in patients with prehypertension.

PMID- 24899480
TI  - [Association between prehypertension and epicardial adipose tissue thickness].

PMID- 24899481
TI  - Prevalence of severe carotid artery stenosis and its association with
      echocardiographic parameters in maintenance hemodialysis patients.
AB  - OBJECTIVES: We aimed to determine the prevalence of significant carotid stenosis
      in maintenance hemodialysis patients and to identify biochemical and
      echocardiographic predictors of significant carotid stenosis in those patients.
      STUDY DESIGN: One hundred and seventeen maintenance hemodialysis patients were
      included in this study. Echocardiography biochemical tests and carotid artery
      Doppler ultrasonography were performed in all patients. Data obtained from
      patients without severe carotid stenosis were compared with those obtained from
      patients with severe carotid stenosis. RESULTS: The mean age of the patients was
      56.9+/-12.2 years. Eleven patients had carotid artery stenosis (9.4%). While
      there was a trend of higher left ventricle end diastolic diameter in severe
      carotid artery stenosis (p=0.06), no statistically significant biochemical or
      echocardiographic differences were noted between the patients. CONCLUSION: This
      study demonstrated that the prevalence of carotid artery stenosis is 5-10- fold
      higher than in the general population. All patients in a chronic hemodialysis
      program should be screened for carotid artery stenosis for prevention of
      cerebrovascular diseases.

PMID- 24899482
TI  - Cardiac tamponade as the first clinical sign of gastric adenocarcinoma: a rare
      condition.
AB  - Cardiac tamponade originating from a primary gastric cancer (GC) is a rare
      condition. Patients are generally asymptomatic until the disease is advanced. We
      report a rare patient with cardiac tamponade as the first manifestation of
      primary GC. A 46-year-old male was admitted with progressive dyspnea. Cardiac
      tamponade was diagnosed on two-dimensional ultrasonographic echocardiography.
      Pericardiocentesis yielded 1500 ml of bloody fluid. Pericardial cytologic
      examination was positive for malignant cells. The patient underwent abdominal
      computed tomography scan, which showed thickening of the gastric wall and several
      mesenteric lymph nodes. Endoscopic examination of the stomach disclosed malignant
      ulcer along the lesser curvature, and the biopsy showed diffuse type
      adenocarcinoma. Chemotherapy was initiated by the Oncology Department, and he had
      no pericardial effusion after six courses of systemic chemotherapy. In
      conclusion, this is a rare condition and difficult to diagnosis early. Thus,
      physicians should be aware of malignancy of the stomach when patients present
      with unexplained cardiac manifestations. 

PMID- 24899483
TI  - Rapid retraction of a post-infarction intramyocardial dissecting hematoma.
AB  - A 60-year-old male with a recent anterior myocardial infarction (MI) was referred
      to our hospital for implantable cardioverter defibrillator (ICD) implantation. He
      was on the 42nd day of MI and clinically stable on admission. Electrocardiography
      showed right bundle branch block with QS pattern on anterior leads. Transthoracic
      echocardiographic examination revealed an ejection fraction of 25% with akinesis
      of the apex and mid-apical segments of anterior and septal walls. In the apical
      septal region, a pulsatile cavity with systolic expansion surrounded by a thin
      endomyocardial border was visualized. Color-Doppler interrogation did not
      demonstrate any flow within that structure. These findings suggested an
      intramyocardial dissecting hemorrhage formed after MI. Cardiac magnetic resonance
      imaging also confirmed an intramyocardial hematoma in the mid-apical anteroseptal
      region. A conservative approach was assumed as the patient was hemodynamically
      stable. The planned ICD implantation was postponed due to the high risk of
      perforation. Subsequently, oral anticoagulant therapy with warfarin was initiated
      against risk of intracardiac thrombus formation. The existing dual antiplatelet
      therapy was also continued. One week after hospital discharge, he was
      rehospitalized due to a very high INR of 6.3. The repeated transthoracic
      echocardiography revealed an almost complete resolution of the intramyocardial
      dissecting hematoma and adhesion of the surrounding myocardial layers. Oral
      anticoagulant therapy was discontinued. Echocardiographic examinations showed no
      change compared to the last examination during hospitalization. This case
      illustrates a conservatively managed intramyocardial dissecting hematoma case, in
      which anticoagulant and antiaggregant therapy yielded a rapid retraction without
      any complication. 

PMID- 24899485
TI  - [A rare cause of pulmonary hypertension: bilateral pulmonary artery involvement
      and stent restenosis due to Takayasu arteritis].
AB  - A 53-year-old female patient was admitted with dyspnea and fatigue. On
      transthoracic echocardiography, systolic pulmonary artery pressure (PAP) was
      measured as 90 mmHg, and right heart catheterization revealed pulmonary arterial
      hypertension. Pulmonary angiography demonstrated bilateral pulmonary artery
      stenosis, and the diagnosis was determined as Takayasu arteritis. Balloon
      angioplasty was performed under corticosteroid and immunosuppressive treatment.
      In this case report, we describe a patient in whom bilateral pulmonary artery
      stenosis developed due to Takayasu arteritis, and we discuss the patient in light
      of the current literature. 

PMID- 24899484
TI  - [Subclavian steal-carotid recovery phenomenon due to innominate artery occlusion:
      Doppler ultrasound and digital subtraction angiography findings and endovascular
      treatment].
AB  - Innominate artery occlusion is a rare condition that can cause symptoms in the
      anterior cerebral circulation, vertebrobasilar system and upper extremity, while
      it can also be asymptomatic. We report the Doppler ultrasound and digital
      subtraction angiography (DSA) findings of the right subclavian artery and right
      common carotid artery flow by retrograde flow from the ipsilateral vertebral
      artery due to innominate artery occlusion. We aimed to discuss the results of
      primary stenting together with the technical and clinical success. 

PMID- 24899486
TI  - Disappearance of myocardial bridging of the left anterior descending coronary
      artery after inferior myocardial infarction.
AB  - Myocardial bridging (MB) is defined as the intramural course of a major
      epicardial coronary artery, and is mostly confined to the left ventricle and the
      left anterior descending coronary artery (LAD). MB is a common congenital
      abnormality of a coronary artery, and is usually thought to be a benign
      anatomical variant. Although rare, previous studies have reported that patients
      with MB may suffer from myocardial ischemia, myocardial infarction (MI),
      arrhythmias, and even sudden death. Therefore, the diagnosis and treatment of MB
      are both important. Since MB is congenital, its disappearance is unlikely. We
      here report a very rare case of disappearance of MB after inferior MI. 

PMID- 24899487
TI  - Unilateral absence of the left pulmonary artery with patent ductus arteriosus and
      interrupted inferior vena cava.
AB  - Unilateral absence of the pulmonary artery and interrupted inferior vena cava are
      rare congenital disorders. The clinical presentation is variable, and many
      patients can be asymptomatic for many years and even throughout their lives. We
      report the case of a 44-year-old female patient with a history of hemoptysis. She
      was referred to our clinic with a diagnosis of pulmonary artery agenesis.
      Computed tomography revealed absence of the left main pulmonary artery and long
      tract patent ductus arteriosus (PDA). Blood supply to the left lung was provided
      by major aortopulmonary collateral arteries (MAPCAs). Right heart catheterization
      through the right femoral vein was problematic, as the catheter could not be
      negotiated from the inferior vena cava to the right atrium. We revealed the
      interrupted inferior vena cava, which continued as a dilated azygos vein to the
      superior vena cava. The magnitude of the shunt flow from the PDA was too small,
      and the calculated shunt fraction was not significant. Hemoptysis was possibly
      due to MAPCAs. However, as the patient had no active bleeding when she was
      referred, the exact source of the hemoptysis could not be identified. 

PMID- 24899488
TI  - [Cardiovascular publications in 2013 in Turkey advanced in quantity alone].
AB  - Turkey's institutions in cardiovascular medicine were evaluated regarding
      publication output in 2013 based on data available in the Web of Science. Only
      articles in full-text and reviews appearing in source publications covered by the
      Science Citation Index proper were included. A fractional count system was used
      for items published jointly with a foreign or a non-cardiological Turkish
      institution. Turkey's publications increased numerically to 268, and its global
      share from 4.3 to 6.0 per mille, yet only to the level of 2001. Articles
      originating from adult cardiology numbered 188 (70%), while cardiovascular
      surgery and pediatric cardiology contributed 15% each. Three hospitals affiliated
      with the Ministry of Health (Kartal Kosuyolu, M. Akif Ersoy and Turkiye Yuksek
      Ihtisas Hastanesi) and the cardiology departments of the medical faculties of
      Baskent, Hacettepe and Ege Universities ranked highest, each generating 7-15
      papers. The median impact factor remained similar to the preceding year, at 1.52
      (interquartile range 1.20-2.31). The undertaking of promotional and supportive
      measures by the central authorities regarding the conspicuous decline in Turkey's
      medical research output is long overdue.

PMID- 24899489
TI  - Case images: PR interval prolongation induced by ventricular extrasystole: an
      interesting electrocardiogram.

PMID- 24899490
TI  - Case images: A case with prolapse of all four cardiac valves: a rare condition in
      myxomatous degeneration.

PMID- 24899491
TI  - Case images: Stabilization of a slipping balloon during the treatment of in-stent
      severe restenosis--anchoring the balloon shaft in the guiding catheter.

PMID- 24899492
TI  - Case images: Isolated thrombus-like mass in a patient with multiple myeloma.

PMID- 24899493
TI  - Case images: Cardiogenic shock caused by huge para-aortic hematoma and
      pseudoaneurysm after Bentall operation.

PMID- 24899494
TI  - [Neutrophil to lymphocyte ratio is associated with more extensive, severe and
      complex coronary artery disease and impaired myocardial perfusion].

PMID- 24899495
TI  - [ Authors' reply].

PMID- 24899496
TI  - [New FIGO classification of ovarian, fallopian tube and primary peritoneal
      cancer].
AB  - During recent years paramount changes have occurred in the pathogenesis of
      ovarian cancer and recent clinical studies identified new prognostic factors.
      Consequently, the FIGO has established a new staging system collectively covering
      carcinomas derived from the ovaries, the fallopian tubes and primary peritoneal
      cancers as well as malignant ovarian germ cell and sex-cord stromal tumors. The
      new staging system started on 01 January 2014. Major changes occurred in the FIGO
      IC/T1c stage with surgical spill (FIGO IC1/T1c1) versus capsule ruptured before
      surgery or tumor on ovarian or fallopian tube surface (FIGO IC2/T1c2) versus
      malignant cells in the ascites or peritoneal washings (FIGO IC3/T1c3). The
      regional lymph node metastases were subcategorised using a cut-off value of 10 mm
      as the largest dimension of the metastatic deposits. Distant metastases
      (excluding peritoneal metastases) were substaged as FIGO IVA/M1a in cases of
      cytologically or histologically proven pleural involvement and as FIGO IVB/M1b in
      cases of parenchymal metastases and metastases in extra-abdominal organs
      (including lymph nodes outside the peritoneal cavity and the inguinal lymph
      nodes). 

PMID- 24899497
TI  - Cutting edge: Dexamethasone potentiates the responses of both regulatory T cells
      and B-1 cells to antigen immunization in the ApoE(-/-) mouse model of
      atherosclerosis.
AB  - The immunosuppressant dexamethasone was shown to preferentially deplete CD4+
      effector T cells while sparing regulatory T cells (Tregs) in vivo. In the current
      study, we show that it also preferentially depletes B-2 cells while sparing B-1
      cells. In the ApoE(-/-) mouse model of atherosclerosis, in which both Tregs and B
      1 cells are thought to play an atheroprotective role, we show that HSP60-targeted
      immunization in the presence of dexamethasone raises Ag-reactive Tregs and B-1
      cells concomitantly and reduces the severity of atherosclerosis. These results
      indicate that dexamethasone is an adjuvant that potentiates both the Treg and B-1
      responses to immunogens. This study shows that B-1 cells with a specificity for a
      disease-relevant Ag can be raised in vivo by immunization.

PMID- 24899498
TI  - Superimposed epitopes restricted by the same HLA molecule drive distinct HIV
      specific CD8+ T cell repertoires.
AB  - Superimposed epitopes, in which a shorter epitope is embedded within a longer
      one, can be presented by the same HLA class I molecule. CD8(+) CTL responses
      against such epitopes and the contribution of this phenomenon to immune control
      are poorly characterized. In this study, we examined HLA-A*24:02-restricted CTLs
      specific for the superimposed HIV Nef epitopes RYPLTFGWCF (RF10) and RYPLTFGW
      (RW8). Unexpectedly, RF10-specific and RW8-specific CTLs from HIV-1-infected HLA
      A*24:02+ individuals had no overlapping Ag reactivity or clonotypic compositions.
      Single-cell TCR sequence analyses demonstrated that RF10-specific T cells had a
      more diverse TCR repertoire than did RW8-specific T cells. Furthermore, RF10
      specific CTLs presented a higher Ag sensitivity and HIV suppressive capacity
      compared with RW8-specific CTLs. Crystallographic analyses revealed important
      structural differences between RF10- and RW8-HLA-A*24:02 complexes as well, with
      featured and featureless conformations, respectively, providing an explanation
      for the induction of distinct T cell responses against these epitopes. The
      present study shows that a single viral sequence containing superimposed epitopes
      restricted by the same HLA molecule could elicit distinct CD8+ T cell responses,
      therefore enhancing the control of HIV replication. This study also showed that a
      featured epitope (e.g., RF10) could drive the induction of T cells with high TCR
      diversity and affinity.

PMID- 24899499
TI  - Porcine cathelicidins efficiently complex and deliver nucleic acids to
      plasmacytoid dendritic cells and can thereby mediate bacteria-induced IFN-alpha
      responses.
AB  - Cathelicidins constitute potent antimicrobial peptides characterized by a high
      cationic charge that enables strong interactions with nucleic acids. In fact, the
      only human cathelicidin LL-37 triggers rapid sensing of nucleic acids by
      plasmacytoid dendritic cells (pDC). Among the porcine cathelicidins, phylogenetic
      analysis of the C-terminal mature peptide showed that porcine myeloid
      antimicrobial peptide (PMAP)-36 was the most closely related of the 11 porcine
      cathelicidins to human LL-37. Despite several investigations evaluating potent
      antimicrobial functions of porcine cathelicidins, nothing is known about their
      ability to promote pDC activation. We therefore investigated the capacity of the
      proline-arginine-rich 39-aa peptide, PMAP-23, PMAP-36, and protegrin-1 to complex
      with bacterial DNA or synthetic RNA molecules and facilitate pDC activation. We
      demonstrate that these peptides mediate a rapid and efficient uptake of nucleic
      acids within minutes, followed by robust IFN-alpha responses. The highest
      positively charged cathelicidin, PMAP-36, was found to be the most potent peptide
      tested for this effect. The peptide-DNA complexes were internalized and also
      found to associate with the cell membranes of pDC. The amphipathic conformation
      typical of PMAP-36 was not required for IFN-alpha induction in pDC. We also
      demonstrate that PMAP-36 can mediate IFN-alpha induction in pDC stimulated by
      Escherichia coli, which alone fail to activate pDC. This response was weaker with
      a scrambled PMAP-36, relating to its lower antimicrobial activity. Collectively,
      our data suggest that the antimicrobial and nucleic acid-complexing properties of
      cathelicidins can mediate pDC activation-promoting adaptive immune responses
      against microbial infections. 

PMID- 24899500
TI  - T cell-intrinsic function of the noncanonical NF-kappaB pathway in the regulation
      of GM-CSF expression and experimental autoimmune encephalomyelitis pathogenesis.
AB  - The noncanonical NF-kappaB pathway induces processing of the NF-kappaB2 precursor
      protein p100, and thereby mediates activation of p52-containing NF-kappaB
      complexes. This pathway is crucial for B cell maturation and humoral immunity,
      but its role in regulating T cell function is less clear. Using mutant mice that
      express a nonprocessible p100, NF-kappaB2(lym1), we show that the noncanonical NF
      kappaB pathway has a T cell-intrinsic role in regulating the pathogenesis of a T
      cell-mediated autoimmunity, experimental autoimmune encephalomyelitis (EAE).
      Although the lym1 mutation does not interfere with naive T cell activation, it
      renders the Th17 cells defective in the production of inflammatory effector
      molecules, particularly the cytokine GM-CSF. We provide evidence that p52 binds
      to the promoter of the GM-CSF-encoding gene (Csf2) and cooperates with c-Rel in
      the transactivation of this target gene. Introduction of exogenous p52 or GM-CSF
      to the NF-kappaB2(lym1) mutant T cells partially restores their ability to induce
      EAE. These results suggest that the noncanonical NF-kappaB pathway mediates
      induction of EAE by regulating the effector function of inflammatory T cells. 

PMID- 24899501
TI  - Membrane association of the CD3epsilon signaling domain is required for optimal T
      cell development and function.
AB  - The TCR:CD3 complex transduces signals that are critical for optimal T cell
      development and adaptive immunity. In resting T cells, the CD3epsilon cytoplasmic
      tail associates with the plasma membrane via a proximal basic-rich stretch (BRS).
      In this study, we show that mice lacking a functional CD3epsilon-BRS exhibited
      substantial reductions in thymic cellularity and limited CD4- CD8- double
      negative (DN) 3 to DN4 thymocyte transition, because of enhanced DN4 TCR
      signaling resulting in increased cell death and TCR downregulation in all
      subsequent populations. Furthermore, positive, but not negative, T cell selection
      was affected in mice lacking a functional CD3epsilon-BRS, which led to limited
      peripheral T cell function and substantially reduced responsiveness to influenza
      infection. Collectively, these results indicate that membrane association of the
      CD3epsilon signaling domain is required for optimal thymocyte development and
      peripheral T cell function.

PMID- 24899503
TI  - NK cell responses to simian immunodeficiency virus vaginal exposure in naive and
      vaccinated rhesus macaques.
AB  - NK cell responses to HIV/SIV infection have been well studied in acute and
      chronic infected patients/monkeys, but little is known about NK cells during
      viral transmission, particularly in mucosal tissues. In this article, we report a
      systematic study of NK cell responses to high-dose vaginal exposure to SIVmac251
      in the rhesus macaque female reproductive tract (FRT). Small numbers of NK cells
      were recruited into the FRT mucosa following vaginal inoculation. The influx of
      mucosal NK cells preceded local virus replication and peaked at 1 wk and, thus,
      was in an appropriate time frame to control an expanding population of infected
      cells at the portal of entry. However, NK cells were greatly outnumbered by
      recruited target cells that fuel local virus expansion and were spatially
      dissociated from SIV RNA+ cells at the major site of expansion of infected
      founder populations in the transition zone and adjoining endocervix. The number
      of NK cells in the FRT mucosa decreased rapidly in the second week, while the
      number of SIV RNA+ cells in the FRT reached its peak. Mucosal NK cells produced
      IFN-gamma and MIP-1alpha/CCL3 but lacked several markers of activation and
      cytotoxicity, and this was correlated with inoculum-induced upregulation of the
      inhibitory ligand HLA-E and downregulation of the activating receptor CD122/IL
      2Rbeta. Examination of SIVDeltanef-vaccinated monkeys suggested that recruitment
      of NK cells to the genital mucosa was not involved in vaccine-induced protection
      from vaginal challenge. In summary, our results suggest that NK cells play, at
      most, a limited role in defenses in the FRT against vaginal challenge.

PMID- 24899502
TI  - Coordinated histone H3 methylation and acetylation regulate physiologic and
      pathologic fas ligand gene expression in human CD4+ T cells.
AB  - Activation-induced Fas ligand (FasL) mRNA expression in CD4+ T cells is mainly
      controlled at transcriptional initiation. To elucidate the epigenetic mechanisms
      regulating physiologic and pathologic FasL transcription, TCR stimulation
      responsive promoter histone modifications in normal and alcohol-exposed primary
      human CD4+ T cells were examined. TCR stimulation of normal and alcohol-exposed
      cells led to discernible changes in promoter histone H3 lysine trimethylation, as
      documented by an increase in the levels of transcriptionally permissive histone 3
      lysine 4 trimethylation and a concomitant decrease in the repressive histone 3
      lysine 9 trimethylation. Moreover, acetylation of histone 3 lysine 9 (H3K9), a
      critical feature of the active promoter state that is opposed by histone 3 lysine
      9 trimethylation, was significantly increased and was essentially mediated by the
      p300-histone acetyltransferase. Notably, the degree of these coordinated histone
      modifications and subsequent recruitment of transcription factors and RNA
      polymerase II were significantly enhanced in alcohol-exposed CD4+ T cells and
      were commensurate with the pathologic increase in the levels of FasL mRNA. The
      clinical relevance of these findings is further supported by CD4+ T cells
      obtained from individuals with a history of heavy alcohol consumption, which
      demonstrate significantly greater p300-dependent H3K9 acetylation and FasL
      expression. Overall, these data show that, in human CD4+ T cells, TCR stimulation
      induces a distinct promoter histone profile involving a coordinated cross-talk
      between histone 3 lysine 4 and H3K9 methylation and acetylation that dictates the
      transcriptional activation of FasL under physiologic, as well as pathologic,
      conditions of alcohol exposure.

PMID- 24899504
TI  - Cutting edge: Vitamin D regulates lipid metabolism in Mycobacterium tuberculosis
      infection.
AB  - Vitamin D has long been linked to resistance to tuberculosis, an infectious
      respiratory disease that is increasingly hard to treat because of multidrug
      resistance. Previous work established that vitamin D induces macrophage
      antimicrobial functions against Mycobacterium tuberculosis. In this article, we
      report a novel, metabolic role for vitamin D in tuberculosis identified through
      integrated transcriptome and mechanistic studies. Transcriptome analysis revealed
      an association between vitamin D receptor (VDR) and lipid metabolism in human
      tuberculosis and infected macrophages. Vitamin D treatment of infected
      macrophages abrogated infection-induced accumulation of lipid droplets, which are
      required for intracellular M. tuberculosis growth. Additional transcriptomics
      results showed that vitamin D downregulates the proadipogenic peroxisome
      proliferator-activated receptor gamma (PPARgamma) in infected macrophages.
      PPARgamma agonists reversed the antiadipogenic and the antimicrobial effects of
      VDR, indicating a link between VDR and PPARgamma signaling in regulating both
      vitamin D functions. These findings suggest the potential for host-based, adjunct
      antituberculosis therapy targeting lipid metabolism. 

PMID- 24899506
TI  - Inhibition of bone remodeling in young mice by bisphosphonate displaces the
      plasma cell niche into the spleen.
AB  - The bone marrow provides niches for early B cell differentiation and long-lived
      plasma cells. Therefore, it has been hypothesized that perturbing bone
      homeostasis might impact B cell function and Ab production. This hypothesis is
      highly relevant for patients receiving long-term treatment with antiresorptive
      drugs. We therefore analyzed the humoral immune response of mice chronically
      treated with ibandronate, a commonly used bisphosphonate. We confirmed the
      increased bone mass caused by inhibition of osteoclast activity and also the
      strongly reduced bone formation because of decreased osteoblast numbers in
      response to ibandronate. Thus, bisphosphonate drastically inhibited bone
      remodeling. When ibandronate was injected into mice after a primary immunization
      to mimic common antiosteoporotic treatments, the generation of the various B cell
      populations, the response to booster immunization, and the generation of plasma
      cells were surprisingly normal. Mice also responded normally to immunization when
      ibandronate was applied to naive mice. However, there, ibandronate shunted the
      homing of bone marrow plasma cells. Interestingly, ibandronate reduced the
      numbers of megakaryocytes, a known component of the bone marrow plasma cell
      niche. In line with normal Ab responses, increased plasma cell populations
      associated with increased megakaryocyte numbers were then observed in the spleens
      of the ibandronate-treated mice. Thus, although inhibition of bone remodeling
      disturbed the bone marrow plasma cell niche, a compensatory niche may have been
      created by relocating the megakaryocytes into the spleen, thereby allowing normal
      B cell responses. Therefore, megakaryocytes may act as a key regulator of plasma
      cell niche plasticity. 

PMID- 24899505
TI  - Specific microbiota-induced intestinal Th17 differentiation requires MHC class II
      but not GALT and mesenteric lymph nodes.
AB  - IL-17-expressing CD4+ T lymphocytes (Th17 cells) naturally reside in the
      intestine where specific cytokines and microbiota, such as segmented filamentous
      bacteria (SFB), promote their differentiation. Intestinal Th17 cells are thought
      to initially differentiate in the GALT and/or mesenteric lymph nodes upon Ag
      encounter and subsequently home to the lamina propria (LP) where they mediate
      effector functions. However, whether GALT and/or mesenteric lymph nodes are
      required for intestinal Th17 differentiation as well as how microbiota containing
      SFB regulate Ag-specific intestinal Th17 cells remain poorly defined. In this
      study, we observed that naive CD4+ T cells were abundant in the intestinal LP
      prior to weaning and that the accumulation of Th17 cells in response to
      microbiota containing SFB occurred in the absence of lymphotoxin-dependent
      lymphoid structures and the spleen. Furthermore, the differentiation of
      intestinal Th17 cells in the presence of microbiota containing SFB was dependent
      on MHC class II expression by CD11c+ cells. Lastly, the differentiation of Ag
      specific Th17 cells required both the presence of cognate Ag and microbiota
      containing SFB. These findings suggest that microbiota containing SFB create an
      intestinal milieu that may induce Ag-specific Th17 differentiation against food
      and/or bacterial Ags directly in the intestinal LP.

PMID- 24899507
TI  - Modeling the clinical phenotype of BTK inhibition in the mature murine immune
      system.
AB  - Inhibitors of Bruton's tyrosine kinase (BTK) possess much promise for the
      treatment of oncologic and autoimmune indications. However, our current knowledge
      of the role of BTK in immune competence has been gathered in the context of
      genetic inactivation of btk in both mice and man. Using the novel BTK inhibitor
      PF-303, we model the clinical phenotype of BTK inhibition by systematically
      examining the impact of PF-303 on the mature immune system in mice. We implicate
      BTK in tonic BCR signaling, demonstrate dependence of the T3 B cell subset and
      IgM surface expression on BTK activity, and find that B1 cells survive and
      function independently of BTK. Although BTK inhibition does not impact humoral
      memory survival, Ag-driven clonal expansion of memory B cells and Ab-secreting
      cell generation are inhibited. These data define the role of BTK in the mature
      immune system and mechanistically predict the clinical phenotype of chronic BTK
      inhibition. 

PMID- 24899508
TI  - The role of the Syk/Shp-1 kinase-phosphatase equilibrium in B cell development
      and signaling.
AB  - Signal transduction from the BCR is regulated by the equilibrium between kinases
      (e.g., spleen tyrosine kinase [Syk]) and phosphatases (e.g., Shp-1). Previous
      studies showed that Syk-deficient B cells have a developmental block at the
      pro/pre-B cell stage, whereas a B cell-specific Shp-1 deficiency promoted B-1a
      cell development and led to autoimmunity. We generated B cell-specific Shp-1 and
      Syk double-knockout (DKO) mice and compared them to the single-knockout mice
      deficient for either Syk or Shp-1. Unlike Syk-deficient mice, the DKO mice can
      generate mature B cells, albeit at >20-fold reduced B cell numbers. The DKO B-2
      cells are all Syk-negative, whereas the peritoneal B1 cells of the DKO mice still
      express Syk, indicating that they require this kinase for their proper
      development. The DKO B-2 cells cannot be stimulated via the BCR, whereas they are
      efficiently activated via TLR or CD40. We also found that in DKO pre-B cells, the
      kinase Zap70 is associated with the pre-BCR, suggesting that Zap70 is important
      to promote B cell maturation in the absence of Syk and SHP-1. Together, our data
      show that a properly balanced kinase/phosphatase equilibrium is crucial for
      normal B cell development and function. 

PMID- 24899510
TI  - When the mandatory second opinion fails to approve compulsory treatment.
AB  - OBJECTIVES: To examine situations in which compulsory treatment was not approved
      by the second opinion required under New Zealand's Mental Health Act. METHODS:
      Qualitative and quantitative analysis of 11 index cases where full approval of
      treatment was not given and of 33 matched controls. RESULTS: The reasons for non
      approval of treatment were diverse. Following non-approval, intensive
      consultation occurred, reflecting significant disagreement between clinicians.
      The process of resolution included discharge from the Act, patients consenting to
      treatment and alternative treatment plans. Compared with controls, index cases
      had significantly lower rates of being mentally well in the community over the
      subsequent year. CONCLUSIONS: Non-approval marks a group of patients with very
      poor clinical outcome. Explicit processes are needed to manage non-approval of
      compulsory treatment plans.

PMID- 24899509
TI  - Nuclear retention of Fbw7 by specific inhibitors of nuclear export leads to
      Notch1 degradation in pancreatic cancer.
AB  - Chromosome maintenance region 1 (CRM1) also called Exportin 1 (Xpo1), a protein
      found elevated in pancreatic ductal adenocarcinoma (PDAC), blocks tumor
      suppressor protein (TSP) function through constant nuclear export. Earlier we had
      shown that targeting CRM1 by our newly developed specific inhibitors of nuclear
      export (SINE) leads to inhibition of pancreatic cancer cell proliferation and
      tumor growth arrest. In this paper we define the mechanism of SINE action. Our
      lead SINE KPT-185 inhibits PDAC cell growth, cell migration, tumor invasion and
      induces apoptosis and G2-M cell cycle arrest in low nano molar range (IC50s~150
      nM). Mechanistically we demonstrate that the activity of KPT-185 is associated
      with nuclear retention of Fbw7; which degrades nuclear Notch-1 leading to
      decreased tumor promoting markers such as C-Myc, Cyclin-D1, Hes1 and VEGF. The
      orally bioavailable SINE (KPT-251) showed potent anti-tumor activity in a Colo
      357 PDAC xenografts model; residual tumor analysis showed activation of Fbw7
      concomitant with attenuation of Notch1 and its downstream genes. These results
      suggest that the antitumor activity of KPT-185 is in part due to nuclear
      retention of Fbw7 and consequent Notch1 degradation. The new CRM1 inhibitors,
      therefore, hold strong potential and warrant further clinical investigations for
      PDAC. 

PMID- 24899512
TI  - Diving to the foot of an iceberg: the SEARCH for undiagnosed atrial fibrillation.

PMID- 24899511
TI  - Cancer patients' perceptions regarding the value of the physical examination: a
      survey study.
AB  - BACKGROUND: Despite its clinical utility, progressive reliance on technology can
      lead to devaluing the physical examination in patients with advanced cancer. The
      primary objective of this study was to determine whether these patients have a
      positive or negative perception of the physical examination. A secondary
      objective was to determine whether these perceptions are related to
      interpersonal/relational values (symbolic) or diagnostic/objective values
      (pragmatic). METHODS: One hundred fifty patients with cancer who were receiving
      concurrent oncology and palliative care were administered a 26-item survey
      regarding their overall perception of the physical examination. The primary
      outcome-patient responses to "In the last 3 months, I believe my experience while
      being examined has been overall: very negative (a score of -5) to very positive
      (a score of +5),"-was analyzed using the Sign test. Other items were predefined
      as either symbolic or pragmatic statements, and patient responses from strongly
      disagree (a score of 1) to strongly agree (a score of 5) were further analyzed.
      Multivariable logistic regression was used to test for associations between
      baseline characteristics and the primary outcome. RESULTS: Most patients (83%)
      indicated that the overall experience of being examined was highly positive
      (median score, 4; interquartile range [IQR], 2-5; P <= .0001). Patients valued
      both the pragmatic aspects (median score, 5; IQR, 4-5) and symbolic aspects
      (median score, 4; IQR, 4-5) of the physical examination. Increasing age was
      independently associated with a more positive perception of the physical
      examination (odds ratio, 1.07 per year; 95% confidence interval, 1.02-1.12 per
      year; P = .01). CONCLUSIONS: Patients with advanced cancer indicate that the
      physical examination is a highly positive aspect of their care. These benefits
      are perceived as having both symbolic and pragmatic value. The physical
      examination should remain a cornerstone of clinical encounters.

PMID- 24899513
TI  - Evaluation of the effect of fluorination on the property of monofluorinated
      dimyristoylphosphatidylcholines.
AB  - The synthesis of three monofluorinated dimyristoylphosphatidylcholines (F
      DMPC's), with the fluorine atom located at the extremities of the acyl chain in
      position 2 of the glycerol (sn-2), is described. The synthetic strategy relies on
      the coupling of 1-myristoyl-2-hydroxy-sn-glycero-3-phosphocholine (14:0 lyso-PC)
      and three different fluorinated fatty acids. FTIR results suggest that the
      presence of the fluorine atom does not significantly perturb the lipid phase
      transition temperature and conformational order even though a small increase in
      the phase transition temperature is observed for the 14F derivative. Overall,
      comparison with previously reported F-DMPC's where the fluorine atom is located
      in the middle or close from either side supports the fact that monofluorination
      of the acyl chain in sn-2 brings minimal perturbation to the lipid bilayer. F
      DMPC's could therefore potentially be used as NMR probes for the investigation at
      the molecular level of the interaction between drugs or peptides and lipid
      membranes and for the study of membrane topology. 

PMID- 24899514
TI  - Novel treatments for familial hypercholesterolemia: pharmacogenetics at work.
AB  - The familial hypercholesterolemias (FHs) are inherited disorders of lipoprotein
      metabolism that are among the most prevalent genetically inherited disorders.
      Various genetic mutations ultimately lead to greatly increased low-density
      lipoprotein-cholesterol (LDL-C) levels over a lifetime. Consequently, patients
      with FH develop coronary artery disease at significantly earlier ages and at a
      greater frequency than the general population. Current therapies revolve around
      aggressive lifestyle modifications, cholesterol-lowering medications, and in some
      cases LDL apheresis. Despite maximal medical therapy, LDL-C is not sufficiently
      reduced in some patients, and they remain at a substantially increased risk of
      coronary heart disease. Recent advances in genetic-based pharmacology have
      enabled the development of three novel classes of medications for FH. Two of
      those compounds, mipomersen and lomitapide, result in decreased LDL-C production
      and were approved by the Food and Drug Administration in the past 18 months for
      treatment of homozygous FH. Mipomersen is an antisense oligonucleotide that
      inhibits the translation of apolipoprotein B-100, and lomitapide is an inhibitor
      of the microsomal triglyceride transfer protein, which prevents the incorporation
      of triglycerides into lipoproteins. A third class of drugs, the proprotein
      convertase subtilisin/kexin type 9 inhibitors, is still in development, although
      studies in patients with heterozygous or receptor-defective homozygous FH have
      demonstrated substantial reductions in LDL-C by decreasing the degradation of LDL
      receptors. Development of these novel treatments for hypercholesterolemia
      resulted from the application of known genetic mutations and is the focus of this
      review.

PMID- 24899515
TI  - Masculinity in adolescent males' early romantic and sexual heterosexual
      relationships.
AB  - There is a need to understand better the complex interrelationship between the
      adoption of masculinity during adolescence and the development of early romantic
      and sexual relationships. The purpose of this study was to describe features of
      adolescent masculinity and how it is expressed in the contexts of early to middle
      adolescent males' romantic and sexual relationships. Thirty-three 14- to 16-year
      old males were recruited from an adolescent clinic serving a community with high
      sexually transmitted infection rates and were asked open-ended questions about
      their relationships-how they developed, progressed, and ended. Participants
      described a high degree of relationally oriented beliefs and behaviors related to
      romantic and sexual relationships, such as a desire for intimacy and trust. The
      males also described a more limited degree of conventionally masculine beliefs
      and behaviors. These beliefs and behaviors often coexisted or overlapped.
      Implications for the clinical care of similar groups of adolescents are
      described.

PMID- 24899516
TI  - Unemployment and health: experiences narrated by young Finnish men.
AB  - Studies have shown that the experiences and consequences of unemployment can
      affect people differently depending on, for example, age and gender. The purpose
      of the present study was to describe young Finnish men's experiences of being
      unemployed as well as how their experiences of health emerged. Fifteen young
      unemployed Finnish men in the age range 18 to 27 years were interviewed face to
      face. Purposive sampling was used to increase the variation among informants. The
      interview texts were analyzed using both manifest and latent qualitative content
      analysis. The present results showed that the young men were strongly negatively
      affected by being unemployed. They described how they had slowly lost their
      foothold. They also described feelings of shame and guilt as well as a flight
      from reality. The present results show that even young men who have only
      experienced shorter periods of unemployment, in this study periods between 2 and
      6 months, are negatively affected, for example, with regard to their identity and
      emotional life. Further research is needed to describe and elucidate in more
      detail the effects of unemployment on men of different ages and living in
      different contexts. 

PMID- 24899517
TI  - Body-related self-conscious emotions relate to physical activity motivation and
      behavior in men.
AB  - The aim of this study was to examine the associations between the body-related
      self-conscious emotions of shame, guilt, and pride and physical activity
      motivation and behavior among adult males. Specifically, motivation regulations
      (external, introjected, indentified, intrinsic) were examined as possible
      mediators between each of the body-related self-conscious emotions and physical
      activity behavior. A cross-sectional study was conducted with adult men (N = 152;
      Mage = 23.72, SD = 10.92 years). Participants completed a questionnaire assessing
      body-related shame, guilt, authentic pride, hubristic pride, motivational
      regulations, and leisure-time physical activity. In separate multiple mediation
      models, body-related shame was positively associated with external and
      introjected regulations and negatively correlated with intrinsic regulation.
      Guilt was positively linked to external, introjected, and identified regulations.
      Authentic pride was negatively related to external regulation and positively
      correlated with both identified and intrinsic regulations and directly associated
      with physical activity behavior. Hubristic pride was positively associated with
      intrinsic regulation. Overall, there were both direct and indirect effects via
      motivation regulations between body-related self-conscious emotions and physical
      activity (R(2) shame = .15, guilt = .16, authentic pride = .18, hubristic pride =
      .16). These findings highlight the importance of targeting and understanding self
      conscious emotions contextualized to the body and links to motivation and
      positive health behavior among men.

PMID- 24899519
TI  - Concise stereoselective total synthesis of (+)-muricatacin and (+)-epi
      muricatacin.
AB  - Efficient stereoselective total synthesis of (+)-muricatacin (1) and (+)-epi
      muricatacin (8) was accomplished from commercially available chemical pent-4
      ynoic acid via Shi's asymmetric epoxidation and Mitsunobu reaction as the key
      steps in 17.8% and 26.9% overall yields, respectively. 

PMID- 24899518
TI  - Complex reconfiguration of DNA nanostructures.
AB  - Nucleic acids have been used to create diverse synthetic structural and dynamic
      systems. Toehold-mediated strand displacement has enabled the construction of
      sophisticated circuits, motors, and molecular computers. Yet it remains
      challenging to demonstrate complex structural reconfiguration in which a
      structure changes from a starting shape to another arbitrarily prescribed shape.
      To address this challenge, we have developed a general structural-reconfiguration
      method that utilizes the modularly interconnected architecture of single-stranded
      DNA tile and brick structures. The removal of one component strand reveals a
      newly exposed toehold on a neighboring strand, thus enabling us to remove regions
      of connected component strands without the need to modify the strands with
      predesigned external toeholds. By using this method, we reconfigured a two
      dimensional rectangular DNA canvas into diverse prescribed shapes. We also used
      this method to reconfigure a three-dimensional DNA cuboid. 

PMID- 24899520
TI  - Sensitive skin in Brazil and Russia: an epidemiological and comparative approach.
AB  - BACKGROUND: Sensitive skin is characterized by the occurrence of sensations of
      tingling, prickling, heat, burning, pain or itching and, on occasion, erythema,
      in response to multiple physical, chemical or hormonal factors that do not have
      irritant properties by themselves. OBJECTIVE: We chose here to evaluate sensitive
      skin in two countries with very different populations, climates and lifestyles:
      Russia and Brazil. METHOD: Representative nationwide samples of the Russian and
      Brazilian populations aged 15 and over were selected. The same methodology was
      used: the individuals were questioned by telephone and selected as per the quotas
      method (sex, age, householder profession, rural/urban location and region).
      RESULTS: In the Brazilian population, 22.3% versus 45.7%, in favour of women,
      reported having a "sensitive" skin. Significant differences were only observed by
      geographic residence. In the Russian population, 25.4% versus 50.1%, in favour of
      women, reported having a "sensitive" skin. Significant differences were observed
      in skin sensitivity according to social-professional categories, region of
      residence and subject age. The same results were found in both populations for
      sensitivity to cosmetics and food intake. CONCLUSION: Respondents with rather
      sensitive or very sensitive skin are 2 or 3 times more reactive to climatic,
      environmental factors, cosmetics and food intake.

PMID- 24899521
TI  - The Metacognitions about Symptoms Control Scale: Development and Concurrent
      Validity.
AB  - OBJECTIVE: This paper presents the development and preliminary validation of a
      self-report instrument designed to measure metacognitions pertaining to symptoms
      control in the form of the following: (1) symptoms focusing and (2) symptoms
      conceptual thinking. METHODS: A total of 124 patients (95 female and 29 male)
      presenting with chronic fatigue syndrome (CFS) contributed data to the study to
      test the structure and psychometric properties of the Metacognitions about
      Symptoms Control Scale (MaSCS). RESULTS: A principal components factor analysis
      indicated that a two-factor solution best fitted the data. The factors were
      labelled positive and negative metacognitions about symptoms control. Further
      analyses revealed that both factors had good internal consistency. Correlation
      analyses established preliminary concurrent validity, indicating that both
      positive and negative metacognitions about symptoms control were significantly
      associated with levels of fatigue in CFS. Regression analysis revealed that
      positive and negative metacognitions about symptoms control significantly
      predicted fatigue severity when controlling for anxiety and depression.
      CONCLUSIONS: The newly developed instrument may help future research that
      examines the role of metacognitions in CFS, as well as aiding clinical assessment
      and case formulation. KEY PRACTITIONER MESSAGE: The MaSCS is a useful first
      instrument to assess metacognitions in CFS. The MaSCS may help to deepen our
      understanding of symptoms control (symptoms focusing and conceptual thinking
      about symptoms) in the experience of CFS symptoms. Assessing and conceptualizing
      symptoms control through the MaSCS may aid treatment of CFS.

PMID- 24899522
TI  - The transplantation of solid organs from HIV-positive donors to HIV-negative
      recipients: ethical implications.
AB  - HIV-positive individuals have traditionally been barred from donating organs due
      to transmission concerns, but this barrier may soon be lifted in the USA in
      limited settings when recipients are also infected with HIV. Recipients of livers
      and kidneys with well-controlled HIV infection have been shown to have similar
      outcomes to those without HIV, erasing ethical concerns about poorly chosen
      beneficiaries of precious organs. But the question of whether HIV-negative
      patients should be disallowed from receiving an organ from an HIV-positive donor
      has not been adequately explored. In this essay, we will discuss the background
      to this scenario and the ethical implications of its adoption from the
      perspectives of autonomy, beneficence/non-maleficence and justice. 

PMID- 24899523
TI  - Maternal transmission of HIV infection: a crime against my child?
AB  - This paper considers whether section 20 of the Offences Against the Person Act
      1861, which has been used to prosecute those who transmit the HIV virus in sexual
      relationships (eg, R v Konzani), could be used to prosecute women (in England and
      Wales) who transmit the virus to their child during pregnancy, delivery or via
      breast feeding. The discussion concludes that prosecution for transmission in
      pregnancy/delivery is unlikely. However, it is argued that there might be scope
      to prosecute the transmission of the virus via breast feeding in the event that
      there was sufficient evidence. However, this would also be subject to the Crown
      Prosecution Service deeming such a prosecution to be in the public interest. The
      paper does not seek to examine the ethical issues involved. However, it
      acknowledges that this issue is part of a broader debate as to whether, and if
      so, when, it is appropriate to criminalise the transmission of disease. 

PMID- 24899524
TI  - Disruption of heterotypic community development by Porphyromonas gingivalis with
      small molecule inhibitors.
AB  - Porphyromonas gingivalis is one of the main etiological organisms in periodontal
      disease. On oral surfaces P. gingivalis is a component of multispecies biofilm
      communities and can modify the pathogenic potential of the community as a whole.
      Accumulation of P. gingivalis in communities is facilitated by interspecies
      binding and communication with the antecedent colonizer Streptococcus gordonii.
      In this study we screened a library of small molecules to identify structures
      that could serve as lead compounds for the development of inhibitors of P.
      gingivalis community development. Three small molecules were identified that
      effectively inhibited accumulation of P. gingivalis on a substratum of S.
      gordonii. The structures of the small molecules are derived from the marine
      alkaloids oroidin and bromoageliferin and contain a 2-aminoimidazole or 2
      aminobenzimidazole moiety. The most active compounds reduced expression of mfa1
      and fimA in P. gingivalis, genes encoding the minor and major fimbrial subunits,
      respectively. These fimbrial adhesins are necessary for P. gingivalis co-adhesion
      with S. gordonii. These results demonstrate the potential for a small molecular
      inhibitor-based approach to the prevention of diseases associated with P.
      gingivalis.

PMID- 24899525
TI  - Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis.
AB  - BACKGROUND: Type 2 diabetes (T2D) has been shown to increase dementia risk, but
      few studies evaluated the relationship between antidiabetic treatment and
      dementia. METHODS: We followed up 67,731 participants who were nondemented,
      nondiabetic, aged 65 or over at baseline from January 2004 to December 2009, to
      observe the onset of T2D (median follow-up 2.4 years), and to compare the risk of
      the development of dementia associated with particular types of antidiabetic
      medication among participants with T2D who had solely one type of antidiabetic
      agents throughout the follow-up period (median follow-up for participants with
      T2D 3.1 years). RESULTS: The hazard ratio for dementia diagnosis in the new-onset
      T2D participants compared with the non-T2D participants was 1.56 (95%CI: 1.39
      2.18). The relative rate of dementia was 5.31 (95% CI: 1.89-14.96) for
      participants taking thiazolidinediones (n = 28) and 1.22 (95% CI: 0.78-1.91) for
      those taking sulfonylureas (n = 796) compared to those taking metformin (n =
      1,033). The risk of dementia was higher in ever (n = 841) versus never users (n =
      4,579) of thiazolidinediones: 1.44 (95% CI: 1.12-1.86). CONCLUSIONS: Diabetes is
      associated with an increased risk of dementia. The risk effect becomes weaker
      provided that participants take sulfonylureas or metformin rather than
      thiazolidinediones for a longer period.

PMID- 24899527
TI  - Hydrogen-bonded and reduction-responsive micelles loading atorvastatin for
      therapy of breast cancer metastasis.
AB  - Metastasis is one of the major obstacles for the successful therapy of breast
      cancer. Although increased candidate drugs targeting cancer metastasis are
      tested, their clinical translation is limited by either serve toxicity or low
      efficacy. In present work, a nano-drug delivery system loading atorvastatin
      calcium (Ator) was developed for the efficient suppression of the metastasis of
      breast cancer. The nano-drug delivery system was constructed by a amphiphilic
      copolymer of methoxy polyethylene glycol-s-s-vitamin E succinate (mPEG-s-s-VES,
      PSV), which was consisted of a hydrophilic mPEG1k segment and a hydrophobic VES
      head, which were conjugated with a linker bearing amide and disulfide groups
      simultaneously. Self-assembly of PSV and Ator formed Ator-loaded PSV micelles
      (ASM) with good colloidal stability, high drug loading content (up to 50%) and
      great encapsulation efficiency (99.09 +/- 0.28%). In cellular level, it was found
      that the ASM could efficiently release the Ator payload into cytosol due to
      detachment of PEG shell at high intracellular glutathione condition. ASM could
      significantly inhibit the migration and invasion of 4T1 breast cancer cells with
      inhibitory rates of 79.2% and 88.5%, respectively. In a 4T1 orthotropic mammary
      tumor metastatic cancer model, it was demonstrated that ASM could completely
      blocked the lung and liver metastasis of breast cancer with minimal toxicity
      owing to enhanced Ator accumulation in tumor and lung as compared with that of
      free Ator. The down-regulations of metastasis-promoting MMP-9, Twist and uPA
      proteins were demonstrated as the main underlying mechanism. As a result, ASM
      could be a promising drug delivery system for the efficient therapy of breast
      cancer metastasis. 

PMID- 24899526
TI  - Serum 25-hydroxyvitamin d and the onset of late-life depressive mood in older men
      and women: the Pro.V.A. study.
AB  - INTRODUCTION: Biological evidence suggests that vitamin D might be involved in
      regulating mood. The relationship between 25-hydroxyvitamin D (25OHD) and the
      onset of depressive symptoms was examined over a 4.4-year follow-up in a sample
      of older adults. METHODS: This research was part of the Progetto Veneto Anziani
      (Pro.V.A.), an Italian population-based cohort study on a total of 1,039 women
      and 636 men aged 65 and older. Serum 25OHD levels were measured at baseline.
      Depressive symptoms were assessed with the Geriatric Depression Scale (GDS) at
      the baseline and during the follow-up. Analyses were adjusted for relevant
      confounders, including health and performance status. RESULTS: 25OHD levels
      correlated inversely with baseline GDS scores, but only in women. After
      controlling for confounders, women deficient in vitamin D (25OHD < 50 nmol/L) had
      higher GDS scores than those who were replete (25OHD > 75 nmol/L), with mean [SE]
      GDS scores: 9.57 [0.37] vs 8.31 [0.31], respectively, p = .02. In men, the
      relationship between 25OHD levels and baseline GDS scores was no longer
      significant after controlling for covariates. Adjusted hazard ratios and 95%
      confidence intervals for incident depression in participants who were vitamin D
      deficient vs replete were not statistically significant (hazard ratio: 0.74, 95%
      confidence interval [0.47-1.16] in women; hazard ratio: 0.96 95% confidence
      interval [0.45-2.06] in men). CONCLUSION: Although an independent inverse
      association between 25OHD levels and GDS scores emerged for women on cross
      sectional analysis, vitamin D deficiency showed no direct effect on the onset of
      late-life depressive symptoms in our prospectively studied population. Further
      studies are warranted to clarify the potential influence of vitamin D on
      psychological health.

PMID- 24899529
TI  - Impact of the adjusted dosing regimen of prasugrel for Japanese patients with
      acute coronary syndrome undergoing percutaneous coronary intervention.

PMID- 24899528
TI  - Metabolic syndrome improvement in depression six months after prescribing simple
      hygienic-dietary recommendations.
AB  - BACKGROUND: Changes in diet and exercise have been separately demonstrated to
      improve Depression, although scientific evidence available is scarce. In a
      previously published controlled study, just recommending these and other
      lifestyle measures (sleep restriction and sunlight exposure) in combination once,
      patients experienced improvements in their depressive symptoms six months later.
      In this sample, one in three depressive patients had metabolic syndrome (MetS) at
      baseline. First line treatment of MetS condition is hygienic-dietetic, being
      Mediterranean diet and exercise especially important. Therefore we analyzed if
      lifestyle recommendations also improved their metabolic profile. FINDINGS: During
      the sixth month evaluation, a smaller number of patients from the group receiving
      hygienic-dietary recommendations met MetS criteria comparing with the control
      group. CONCLUSIONS: This study suggests that costless lifestyle recommendations,
      such as exercise and Mediterranean diet, have the capacity to promote both mental
      and physical health in a significant proportion of depressive patients. Further
      research is needed to confirm or discard these preliminary findings.

PMID- 24899530
TI  - Exercise-based cardiac rehabilitation is safe, yet underused in Japan.

PMID- 24899532
TI  - Fellatio in captive brown bears: evidence of long-term effects of suckling
      deprivation?
AB  - Sexually stimulating behaviors that are not linked to reproduction are rare among
      non-human (especially non-primate) mammals. Such behaviors may have a function in
      the hierarchy of social species. In solitary species, such behaviors are more
      enigmatic, and possibly indicative of something abnormal. Here, we report on a
      case of two male brown bears, raised in captivity since being orphaned as cubs,
      which engaged in recurrent fellatio multiple times per day until at least 10
      years old. The roles of provider and receiver in the act remained unchanged, and
      the behavior itself became highly ritualized. The provider always initiated the
      contact involving vigorous penile sucking that appeared to result in ejaculation.
      We suggest that the behavior began as a result of early deprivation of maternal
      suckling, and persisted through life, possibly because it remained satisfying for
      both individuals. This constitutes the first descriptive report of fellatio in
      bears, and suggests that some bears may suffer lifelong behavioral consequences
      from being orphaned at an early age.

PMID- 24899533
TI  - All solution-processed, hybrid light emitting field-effect transistors.
AB  - All solution-processed, high performance hybrid light emitting transistors
      (HLETs) are realized. Using a novel combination of device architecture and
      materials a bilayer device comprised of an inorganic and organic semiconducting
      layer is fabricated and the optoelectronic properties are presented. 

PMID- 24899531
TI  - Troponin I-interacting protein kinase: a novel cardiac-specific kinase, emerging
      as a molecular target for the treatment of cardiac disease.
AB  - Coronary artery disease is the leading cause of death and disability worldwide.
      In patients with acute coronary syndromes, timely and effective myocardial
      reperfusion by percutaneous coronary intervention is the primary treatment of
      choice to minimize the ischemic injury and limit the size of the myocardial
      infarction (MI). However, reperfusion can itself promote cardiomyocyte death,
      which leads to cardiac dysfunction via reperfusion injury. The molecular
      mechanisms of ischemia-reperfusion (IR) injury are not completely understood and
      new drug targets are needed. Recently, we reported that cardiac troponin I
      interacting protein kinase (TNNI3K), a cardiomyocyte-specific kinase, promotes IR
      injury via profound oxidative stress, thereby promoting cardiomyocyte death. By
      using novel genetic animal models and newly developed small-molecule TNNI3K
      inhibitors, we demonstrated that TNNI3K-mediated IR injury occurs through
      impaired mitochondrial function and is in part dependent on p38 MAPK. Here we
      discuss the emerging role of TNNI3K as a promising new drug target to limit IR
      induced myocardial injury. We will also examine the underlying mechanisms that
      drive the profoundly reduced infarct size in mice in whichTNNI3Kis specifically
      deleted in cardiomyocytes. Because TNNI3K is a cardiac-specific kinase, it could
      be an ideal molecular target, as inhibiting it would have little or no effect on
      other organ systems, a serious problem associated with the use of kinase
      inhibitors targeting kinases that are more widely expressed.

PMID- 24899535
TI  - Shock initiated thermal and chemical responses of HMX crystal from ReaxFF
      molecular dynamics simulation.
AB  - To gain an atomistic-level understanding of the thermal and chemical responses of
      condensed energetic materials under thermal shock, we developed a thermal shock
      reactive dynamics (TS-RD) computational protocol using molecular dynamics
      simulation coupled with ReaxFF force field. beta-Octahydro-1,3,5,7-tetranitro
      1,3,5,7-tetrazocane (HMX) was selected as a a target explosive due to its wide
      usage in the military and industry. The results show that a thermal shock
      initiated by a large temperature gradient between the "hot" region and the "cold"
      region results in thermal expansion of the particles and induces a thermal
      mechanical wave propagating back and forth in the system with an averaged
      velocity of 3.32 km s(-1). Heat propagating along the direction of thermal shock
      leads to a temperature increment of the system and thus chemical reaction
      initiation. Applying a continuum reactive heat conduction model combined with the
      temperature distribution obtained from the RD simulation, a heat conduction
      coefficient is derived as 0.80 W m(-1) K(-1). The chemical reaction mechanisms
      during thermal shock were analyzed, showing that the reaction is triggered by N
      NO2 bond breaking followed by HONO elimination and ring fission. The propagation
      rates of the reaction front and reaction center are obtained to be 0.069 and
      0.038 km s(-1), based on the time and spatial distribution of NO2. The pressure
      effect on the thermal shock was also investigated by employing uniaxial
      compression before the thermal shock. We find that compression significantly
      accelerates thermal-mechanical wave propagation and heat conduction, resulting in
      higher temperature and more excited molecules and thus earlier initiation and
      faster propagation of chemical reactions. 

PMID- 24899534
TI  - Genetic characteristics and antimicrobial resistance of Staphylococcus
      epidermidis isolates from patients with catheter-related bloodstream infections
      and from colonized healthcare workers in a Belgian hospital.
AB  - BACKGROUND: Staphylococcus epidermidis is a pathogen that is frequently
      encountered in the hospital environment. Healthcare workers (HCWs) can serve as a
      reservoir for the transmission of S. epidermidis to patients. METHODS: The aim of
      this study was to compare and identify differences between S. epidermidis
      isolated from 20 patients with catheter-related bloodstream infections (CRBSIs)
      and from the hands of 42 HCWs in the same hospital in terms of antimicrobial
      resistance, biofilm production, presence of the intercellular adhesion (ica)
      operon and genetic diversity (pulsed field gel electrophoresis (PFGE), multilocus
      sequence typing (MLST) and staphylococcal cassette chromosome (SCC) mec typing).
      RESULTS: S. epidermidis isolates that caused CRBSI were resistant to
      significantly more non-betalactam drugs than were isolates collected from HCWs.
      Among the 43 mecA positive isolates (26 from HCWs), the most frequent SCCmec type
      was type IV (44%). The ica operon was significantly more prevalent in CRBSI
      isolates than in HCWs (P < 0.05). Weak in vitro biofilm production seemed to
      correlate with the absence of the ica operon regardless of the commensal or
      pathogenic origin of the isolate. The 62 isolates showed high diversity in their
      PFGE patterns divided into 37 different types: 19 harbored only by the CRBSI
      isolates and 6 shared by the clinical and HCW isolates. MLST revealed a total of
      ten different sequence types (ST). ST2 was limited to CRBSI-specific PFGE types
      while the "mixed" PFGE types were ST5, ST16, ST88 and ST153. CONCLUSION: One
      third of CRBSI episodes were due to isolates belonging to PFGE types that were
      also found on the hands of HCWs, suggesting that HCW serve as a reservoir for
      oxacillin resistance and transmission to patients. However, S. epidermidis ST2,
      mecA-positive and icaA-positive isolates, which caused the majority of clinically
      severe CRBSI, were not recovered from the HCW's hands.

PMID- 24899536
TI  - A method for assessing phylogenetic least squares models for shape and other high
      dimensional multivariate data.
AB  - Studies of evolutionary correlations commonly use phylogenetic regression (i.e.,
      independent contrasts and phylogenetic generalized least squares) to assess trait
      covariation in a phylogenetic context. However, while this approach is
      appropriate for evaluating trends in one or a few traits, it is incapable of
      assessing patterns in highly multivariate data, as the large number of variables
      relative to sample size prohibits parametric test statistics from being computed.
      This poses serious limitations for comparative biologists, who must either
      simplify how they quantify phenotypic traits, or alter the biological hypotheses
      they wish to examine. In this article, I propose a new statistical procedure for
      performing ANOVA and regression models in a phylogenetic context that can
      accommodate high-dimensional datasets. The approach is derived from the
      statistical equivalency between parametric methods using covariance matrices and
      methods based on distance matrices. Using simulations under Brownian motion, I
      show that the method displays appropriate Type I error rates and statistical
      power, whereas standard parametric procedures have decreasing power as data
      dimensionality increases. As such, the new procedure provides a useful means of
      assessing trait covariation across a set of taxa related by a phylogeny, enabling
      macroevolutionary biologists to test hypotheses of adaptation, and phenotypic
      change in high-dimensional datasets.

PMID- 24899537
TI  - Intermolecular vibrational energy transfers in liquids and solids.
AB  - Resonant and nonresonant intermolecular vibrational energy transfers in
      KSCN/KSC(13)N/KS(13)C(15)N aqueous and DMF solutions and crystals are studied.
      Both energy-gap and temperature dependent measurements reveal some surprising
      results, e.g. inverted energy-gap dependent energy transfer rates and opposite
      temperature dependences of resonant and nonresonant energy transfer rates. Two
      competing mechanisms are proposed to be responsible for the experimental
      observations. The first one is the dephasing mechanism in which the measured
      energy transfer rate originates from the dephasing of the energy donor-acceptor
      coherence, and the second one is the phonon-compensation mechanism derived from
      the second order perturbation. It is found that both the nonresonant energy
      transfers in the liquids and resonant energy transfers in both liquids and solids
      can be well described by the first mechanism. The second mechanism explains the
      nonresonant energy transfers in one series of the solid samples very well. 

PMID- 24899539
TI  - Profound T-cell defects in Dubowitz syndrome.

PMID- 24899538
TI  - Baroreflex activation: from mechanisms to therapy for cardiovascular disease.
AB  - Recent technical advances have led to the development of a medical device that
      can reliably activate the carotid baroreflex with an acceptable degree of safety.
      Because activation of the sympathetic nervous system plays an important role in
      the pathogenesis of hypertension and heart failure, the unique ability of this
      device to chronically suppress central sympathetic outflow in a controlled manner
      suggests potential value in the treatment of these conditions. This notion is
      supported by both clinical and experimental animal studies, and the major aim of
      this article is to elucidate the physiological mechanisms that account for the
      favorable effects of baroreflex activation therapy in patients with resistant
      hypertension and heart failure. Illumination of the neurohormonal, renal, and
      cardiac actions of baroreflex activation is likely to provide the means for
      better identification of those patients that are most likely to respond favorably
      to this device-based therapy. 

PMID- 24899540
TI  - A simple way to prepare Au@polypyrrole/Fe3O4 hollow capsules with high stability
      and their application in catalytic reduction of methylene blue dye.
AB  - Metal nanoparticles are promising catalysts for dye degradation in treating
      wastewater despite the challenges of recycling and stability. In this study, we
      have introduced a simple way to prepare Au@polypyrrole (PPy)/Fe3O4 catalysts with
      Au nanoparticles embedded in a PPy/Fe3O4 capsule shell. The PPy/Fe3O4 capsule
      shell used as a support was constructed in one-step, which not only dramatically
      simplified the preparation process, but also easily controlled the magnetic
      properties of the catalysts through adjusting the dosage of FeCl2.4H2O. The
      component Au nanoparticles could catalyze the reduction of methylene blue dye
      with NaBH4 as a reducing agent and the reaction rate constant was calculated
      through the pseudo-first-order reaction equation. The Fe3O4 nanoparticles
      permitted quick recycling of the catalysts with a magnet due to their room
      temperature superparamagnetic properties; therefore, the catalysts exhibited good
      reusability. In addition to catalytic activity and reusability, stability is also
      an important property for catalysts. Because both Au and Fe3O4 nanoparticles were
      wrapped in the PPy shell, compared with precursor polystyrene/Au composites and
      bare Fe3O4 nanoparticles, the stability of Au@PPy/Fe3O4 hollow capsules was
      greatly enhanced. Since the current method is simple and flexible to create
      recyclable catalysts with high stability, it would promote the practicability of
      metal nanoparticle catalysts in industrial polluted water treatment. 

PMID- 24899541
TI  - Dornase alpha inhalations as a treatment option for recurrent lower respiratory
      tract infections in a child with Sotos syndrome.
AB  - Recurrent episodes of lower respiratory tract infections (LRTIs) are a rare
      complication of muscular hypotonia in patients with Sotos syndrome. We report on
      a male child suffering from repeated LRTIs including bronchitis, pneumonia, and
      atelectasis during infancy despite inhalations with salbutamol and fluticasone
      combined with manual chest percussion therapy. After initiation of dornase alpha
      inhalations in addition to the current treatment, we observed an improvement in
      the respiratory symptoms as well as a reduction in the rate of hospitalizations
      and in the occurrence of LRTIs. We assume that dornase alpha inhalations, in
      combination with airway clearance techniques, reduced the viscosity of airway
      secretions and by this improved mucociliary clearance and coughing efficiency.

PMID- 24899543
TI  - In vivo protective effects of dietary curcumin and capsaicin against alcohol
      induced oxidative stress.
AB  - BALB/c mice were exposed to chronic alcohol-induced oxidative stress by
      intragastric administration of excessive ethanol (5 g/kg body weight) during the
      24-week period. Curcumin (0.016%) or capsaicin (0.014%) containing diets were fed
      with or without ethanol treatment in four groups. There was no statistically
      significant difference in the behavioral test between all groups during the
      experimental period. Only one alcohol-treated mouse fed a normal diet showed a
      behavioral disorder and died before the raising period was completed. There were
      no effects on the activity of catalase and superoxide dismutase in the brain.
      However, curcumin or capsaicin treatment prevented alcohol-induced decline in
      brain weight. Furthermore, the levels of malondialdehyde and phosphatidylcholine
      hydroperoxide were significantly reduced in the brain tissue extract. The
      findings of this study demonstrated and confirmed the antioxidant effect of
      curcumin and capsaicin against alcohol-induced oxidative stress, and they suggest
      a direction for further studies.

PMID- 24899544
TI  - Plasma matrix metalloproteinase-9 activity in cats with lymphoma.
AB  - In this study, plasma MMP-9 activity was evaluated in cats with lymphoma. Plasma
      samples were obtained from 26 cats with lymphoma before treatment. From 13 of the
      included 26 cats, plasma samples were obtained 4 weeks after the initiation of
      treatment. Plasma samples were also obtained from 10 healthy cats as a control.
      Plasma MMP-9 activity was examined by gelatin zymography and semi-quantitative
      value (arbitrary unit; a.u.) for each sample was calculated. Relatively high
      levels of MMP-9 were observed in cats with lymphoma compared with those in
      healthy control cats. MMP-9 quantification through zymography showed
      significantly higher activity in cats with lymphoma (median, 0.63 a.u.; range,
      0.23-3.24 a.u.) than in healthy controls (0.22 a.u.; 0.12-0.46 a.u.; P < 0.01).
      MMP-9 activities were significantly different before (0.73 a.u.; 0.30-3.24 a.u.)
      and after treatment (0.50 a.u.; 0.14-1.32 a.u.; P = 0.017). Measuring plasma MMP
      9 activity in cats with lymphoma may become an appropriate monitoring tool for
      feline lymphoma.

PMID- 24899545
TI  - Free-floating thrombus in stroke patients with nonstenotic internal carotid
      artery-an ultrasonographic study.
AB  - BACKGROUND: There are multiple causes of free-floating thrombus (FFT) formation
      in carotid arteries. The purpose of this study was to evaluate the incidence and
      natural history of FFT in nonstenotic internal carotid arteries of patients with
      acute ischemic stroke. METHODS: During a 50-month period, 3,200 consecutive
      patients with acute ischemic stroke were evaluated for internal carotid artery
      stenosis and the presence of FFT by color-coded duplex ultrasonography.
      Diagnostic workup included brain CT, transthoracic echocardiography, Holter
      electrocardiogram, and hypercoagulability state evaluation. RESULTS: We found an
      FFT in 5 (0.18%) of 2,757 patients with acute stroke and nonstenotic internal
      carotid artery (mean age 44 years). The underlying pathology was hypercoagulable
      state in active pulmonary tuberculosis (n = 1), essential thrombocythemia (n =
      1), thrombotic complications of nonstenotic plaques (n = 1), unknown (n = 2). All
      patients clinically improved under antiplatelet therapy. Follow-up color-coded
      duplex ultrasonography showed complete dissolution of FFT in all cases. There was
      no stroke recurrence. CONCLUSIONS: Internal carotid artery FFT could be found in
      young stroke patients without identifiable arterial disease and could be resolved
      with antithrombotic treatment.

PMID- 24899546
TI  - Minimal evidence of response shift in the absence of a catalyst.
AB  - BACKGROUND: Individuals with chronic conditions experience fluctuations in health
      status and thus may experience response shift. We sought to test the hypothesis
      that response shift effects would be non-significant among individuals with
      chronic disease who experienced relatively small changes in their health status
      over a 1-year period. METHODS: This secondary analysis utilized longitudinal
      cohort data on a community-based sample (n = 776) representing four chronic
      diseases (arthritis, heart failure, diabetes, or chronic obstructive pulmonary
      disease). Information on health-care utilization was obtained from the provincial
      health insurance database. Participants completed the SF-36 twice annually.
      Parameter invariance over 1 year in a second-order SF-36 factor structure was
      evaluated by adapting Oort's approach by fitting a second-order measurement
      structure with first-order factors for the SF-36 subscales and second-order
      factors for physical and mental health status while accommodating ordinal data.
      RESULTS: Over 80 % of participants had no hospitalizations or emergency room
      visits over follow-up. The model had an acceptable fit when all measurement model
      parameters were constrained at both time points (RMSEA = .035, CFI = .97). There
      was no substantial difference in fit when measurement model parameters (item
      thresholds, first-order factor intercepts, and factor loadings) were allowed to
      vary over time. CONCLUSION: Among chronically ill individuals with stable health,
      substantial response shift effects were not detected. These results support the
      theoretical proposition that response shift is not expected to occur in patients
      with relatively stable conditions.

PMID- 24899547
TI  - Cancer-related fatigue in breast cancer patients: factor mixture models with
      continuous non-normal distributions.
AB  - OBJECTIVE: Fatigue is one of the most prevalent and significant symptoms
      experienced by breast cancer patients. This study aimed to investigate potential
      population heterogeneity in fatigue symptoms of the patients using the innovative
      non-normal mixture modeling. METHODS: A sample of 197 breast cancer patients
      completed the brief fatigue inventory and other measures on cancer symptoms. Non
      normal factor mixture models were analyzed and compared using the normal, t, skew
      normal, and skew-t distributions. Selection of the number of latent classes was
      based on the Bayesian information criterion (BIC). The identified classes were
      validated by comparing their demographic profiles, clinical characteristics, and
      cancer symptoms using a stepwise distal outcome approach. RESULTS: The observed
      fatigue items displayed slight skewness but evident negative kurtosis. Factor
      mixture models using the normal distribution pointed to a 3-class solution. The t
      distribution mixture models showed the lowest BIC for the 2-class model. The
      restored class (52.5 %) exhibited moderate severity (item mean = 2.8-3.2) and low
      interference (item mean = 1.1-1.9). The exhausted class (47.5 %) displayed high
      levels of fatigue severity and interference (item mean = 5.8-6.6). Compared to
      the restored class, the exhausted class reported significantly higher perceived
      stress, anxiety, depression, pain, sleep disturbance, and lower quality of life.
      CONCLUSIONS: The non-normal factor mixture models suggest two distinct subgroups
      of patients on their fatigue symptoms. The presence of the exhausted class with
      exacerbated symptoms calls for a proactive assessment of the symptoms and
      development of tailored interventions for this subgroup.

PMID- 24899548
TI  - Amorfrutins: A promising class of natural products that are beneficial to health.
AB  - The incidence of complex noncommunicable diseases has strongly increased over the
      last several decades in the US, Europe and other parts of the world that have
      adopted a western lifestyle (M. Ezzati, E. Riboli, Science- 2012, 337, 1482-1487;
      S. Smyth, A. Heron, Nat. Med.- 2006, 12, 75). Despite considerable investment in
      the development of new types of drugs, options for the treatment of many common
      diseases remain inadequate. If current trends prevail, the rising incidence of
      disorders such as obesity and type 2 diabetes mellitus (T2DM) will soon result in
      an unsustainable burden on society (World Health Organization Technical Report
      Series- 2000, 894, i-xii, 1-253). Given the difficulty of treating fully
      developed complex disorders, new strategies for early intervention and prevention
      of common diseases are of great interest. Dietary natural products with
      beneficial effects, such as the recently described antidiabetic and lipid
      lowering amorfrutins, could pave the way for efficiently treating and preventing
      metabolic and other complex diseases (C. Weidner, et al. Proc. Natl. Acad. Sci.
      USA- 2012, 109, 7257-7262).

PMID- 24899549
TI  - Triboluminescence and vapor-induced phase transitions in the solids of
      methyltriphenylphosphonium tetrahalomanganate(II) complexes.
AB  - Triboluminescence (TL) of the methyltriphenylphosphonium tetrahalomanganate(II)
      complexes such as bis(methyltriphenylphosphonium) tetrabromomanganate (PMBB) and
      bis(methyltriphenylphosphonium) dibromodichloromanganate (PMBC) was switched ON
      and OFF reversibly by vapors of aprotic and protic solvents, respectively, for
      the first time. Detailed analyses indicate that solids of the PMBB and the PMBC
      undergo phase transitions depending on the environment, which regulate the TL
      activity of these compounds. The combined results of luminescence, powder X-ray
      diffraction, differential scanning calorimetry, and electron paramagnetic
      resonance were used to demonstrate crystal dynamism as well as the TL emission of
      PMBB and PMBC. 

PMID- 24899550
TI  - Late-stage formation of carbon-fluorine bonds.
AB  - In this account, we review work from our lab on the development of methods for
      carbon-fluorine bond formation, with an emphasis on late-stage fluorination of
      functionalized small molecules and synthesis of (18) F-labeled molecules for
      potential use as tracers in positron emission tomography (PET). We attempt to
      highlight reactions that we feel are of particular practical relevance, as well
      as areas of research where there is still significant room for advancement. 

PMID- 24899551
TI  - Earliest colonization events of Rhizophagus irregularis in rice roots occur
      preferentially in previously uncolonized cells.
AB  - Arbuscular mycorrhizal (AM) fungi form a symbiotic association with several plant
      species. An arbuscule, a finely branched structure of AM fungi, is formed in root
      cells and plays essential roles in resource exchange. Because arbuscules are
      ephemeral, host cells containing collapsed arbuscules can be recolonized, and a
      wide region of roots can be continuously colonized by AM fungi, suggesting that
      repetitive recolonization in root cells is required for continuous
      mycorrhization. However, recolonization frequency has not been quantified because
      of the lack of appropriate markers for visualization of the cellular processes
      after arbuscule collapse; therefore, the nature of the colonization sequence
      remains uncertain. Here we observed that a green fluorescent protein (GFP)-tagged
      secretory carrier membrane protein (SCAMP) of rice was expressed even in cells
      with collapsed arbuscules, allowing live imaging coupled with GFP-SCAMP to
      evaluate the colonization and recolonization sequences. The average lifetime of
      intact arbuscules was 1-2 d. Cells with collapsed arbuscules were rarely
      recolonized and formed a new arbuscule during the observation period of 5 d,
      whereas de novo colonization occurred even in close proximity to cells containing
      collapsed arbuscules and contributed to the expansion of the colonized region.
      Colonization spread into an uncolonized region of roots but sparsely into a
      previously colonized region having no metabolically active arbuscule but several
      intercellular hyphae. Therefore, we propose that a previously colonized region
      tends to be intolerant to new colonization in rice roots. Our observations
      highlight the overlooked negative impact of the degeneration stage of arbuscules
      in the colonization sequence. 

PMID- 24899552
TI  - Ectopic expression of RESISTANCE TO POWDERY MILDEW8.1 confers resistance to
      fungal and oomycete pathogens in Arabidopsis.
AB  - Broad-spectrum disease resistance is a highly valuable trait in plant breeding
      and attracts special attention in research. The Arabidopsis gene locus RESISTANCE
      TO POWDERY MILDEW 8 (RPW8) contains two adjacent homologous genes, RPW8.1 and
      RPW8.2, and confers broad-spectrum resistance to powdery mildew. Remarkably, the
      RPW8.2 protein is specifically localized to the extrahaustorial membrane (EHM)
      encasing the feeding structure of powdery mildew whereby RPW8.2 activates
      haustorium-targeted defenses. Here, we show that ectopic expression of the yellow
      fluorescent protein (YFP)-tagged RPW8.1 from the native promoter leads to unique
      cell death lesions and enhances resistance to virulent fungal and oomycete
      pathogens that cause powdery mildew and downy mildew diseases, respectively. In
      powdery mildew-infected plants, RPW8.1-YFP accumulates at higher levels in the
      mesophyll cells underneath the infected epidermal cells where RPW8.2-YFP is
      mainly expressed. This cell type-preferential protein accumulation pattern
      largely correlates with that of H(2)O(2) accumulation, suggesting that RPW8.1 may
      spatially collaborate with RPW8.2 in activation of resistance to powdery mildew.
      Interestingly, when ectopically expressed from the RPW8.2 promoter, RPW8.1-YFP is
      also targeted to the EHM of powdery mildew and the transgenic plants display
      resistance to both powdery mildew and downy mildew. Using YFP as a reporter, we
      further reveal that the RPW8.1 promoter is constitutively active but induced to
      higher levels in cells at the infection site, whereas the RPW8.2 promoter is
      activated specifically in cells at the infection site. Taken together, our
      results suggest that RPW8.1 (and its promoter) is functionally distinct from
      RPW8.2 and may have a higher potential in engineering broad-spectrum resistance
      in plants.

PMID- 24899553
TI  - [Role and function of public health nurses in Taiwan: review of current status
      and future perspectives].
AB  - Public health nursing is a core practice of primary health care. Public health
      nurses (PHNs) in Taiwan act both as individual/family-based primary care
      providers and as population-based community care providers. Previous studies in
      Western countries have shown the role preference of PHNs to be highly influenced
      by the structure of the healthcare system, policies and major programs, and
      health insurance reimbursement mechanisms. Thus, the impact of the health
      transition and related changes in the abovementioned systems should be taken into
      consideration when adjusting the roles and functions of PHNs. The rising
      prevalence of chronic diseases and the multiple burdens caused by diseases is
      making healthcare delivery increasingly complicated. With PHNs no longer able to
      provide "catch-all" services due to manpower shortages, several potential
      specialty areas have opened up to participation and development by community
      nursing. These include psychiatric care, long-term care and palliative care,
      school/workplace health promotion, and disease management in hospitals. It will
      be essential that community nurses bridge the gap in service left by PHNs so that
      PHNs may refocus their job role on the health needs of the community as a whole.
      PHNs should continue to build partnerships with primary care settings and perform
      the key functions of demonstration, support, collaboration, service, and
      surveillance in the community.

PMID- 24899554
TI  - [Health for all--the development of community health nursing and public health
      nursing from the perspective of education].
AB  - The purpose of this article was to examine the development of community health
      nursing and public health nursing in Taiwan from an educational perspective. Key
      issues addressed include: teaching strategies and scopes of practice used in
      community health nursing in Taiwan between 1910 and the 1950s; the philosophical
      foundations for the concepts of "health for all" and "social justice" in Taiwan's
      community health nursing; the five "P"s of community health nursing teaching and
      practice (population, prevention, promotion, policy, and partnership); the core
      competencies and scope of practice of community health nursing proposed by the
      TWNA Community Health Nursing Committee; and the core competencies and the tiers
      of classification proposed by the Quad Council of Public Health Nursing
      Organizations. This article helps to elucidate the inseparable relationship
      between community health nursing education and practice at both the micro and
      macro level and examines possible future directions for community health nursing
      in Taiwan. The author proposes the following recommendations for future community
      health nursing education development in Taiwan: 1) implement competence
      classifications appropriate to each nursing education preparation level, 2)
      promote multidisciplinary cooperation among education, practice, and policy, and
      3) promote collaboration and consensus among community health nursing and public
      health related associations.

PMID- 24899555
TI  - [Reflections on the development of maternal and child health in public health
      nursing in Taiwan].
AB  - Continued global economic difficulties and Taiwan's health insurance scheme have
      focused the domestic healthcare system excessively on medical treatments and made
      this system overly market-oriented. The NHI (national health insurance)
      Reimbursement Policy lacks adequate flexibility to adjust to current health
      needs. The situation constrains the medical service budget and causes nursing
      shortages in hospitals, which in turn marginalizes the public health nurses
      working at health centers. It is important for the government and professional
      associations to establish a public healthcare model that adequately meets the
      needs of the community. In addition to strengthening the role and function of
      public health nurses, a service model must be developed and piloted. This paper
      analyzes the situation and problem of maternal and child healthcare in Taiwan,
      studies the successful experiences of maternal and child healthcare from other
      counties, and then provides recommendations for the future development of public
      health nursing in Taiwan.

PMID- 24899556
TI  - [Taiwan occupational health nursing: practices, policies and future trends].
AB  - The steady evolution of domestic industries and the continued expansion of the
      workforce have outdated Taiwan's traditional model of occupational health
      nursing, which focuses on preventing work-related diseases and ensuring workplace
      safety. Professional-competency evaluations, now widely used within the medical
      and other professional communities to confirm that individuals have mastered
      relevant knowledge and skills, are a fixture in service quality management and
      related strategies. Occupational health nurses have a critical role in promoting
      and ensuring the quality of occupational-health related services. A multifaceted
      strategy is needed to update the domestic model of occupational health nursing.
      This strategy should include: 1) Set professional standards and create standard
      teaching materials for national occupational health nurses; 2) Enhance the
      professional efficacy of nurses in this field; 3) Survey the relevant role
      functions and education/training needs of occupational health nurses; 4) Develop
      relevant elective courses; and 5) Format courses/curricula for e-learning and for
      multimedia platforms. Furthermore, after implementation of this strategy, the
      model should be evaluated in terms of the knowledge and skills acquired by
      occupational health nurses. It is hoped that by reflecting local needs and
      experiences this new model will update the field of occupational health nursing
      to meet the needs of the current and future workplace in Taiwan and increase
      nursing knowledge and skills in order to foster and sustain healthy workplace
      environments.

PMID- 24899557
TI  - [Exploring the effectiveness of a health education program on the stimuli frame
      and on uncertainty in patients with sudden hearing loss].
AB  - BACKGROUND: Uncertainty may limit communication and affect the ability of
      patients to adapt to their illness. A high level of uncertainty in patients
      concurrent with sudden hearing loss has been related to poor comprehension of
      communications and poor illness understanding. Currently, there is no any certain
      standard information sheet in the clinical setting. PURPOSE: This study evaluates
      the effect of a one-to-one oral instruction strategy combined with an information
      sheet firstly on the stimuli frame and then on uncertainty in patients suffering
      from idiopathic sudden sensorineural hearing loss. METHODS: An experimental
      design was employed and 60 patients were randomly assigned to either the
      experimental group (n=28) or the control group (n=32). A structured questionnaire
      that included the stimuli frame of uncertainty and the Mishel uncertainty illness
      scale was used to collect data. All samples received regular care following
      admission to the hospital and received the pretest within 24 hours after
      admission. The experimental group received the one-to-one oral instruction
      strategy combined with an information sheet immediately after the pretest. All
      participants completed the posttest three days later. RESULTS: The health
      education program increased perceived understanding of illness in patients with
      the sudden hearing loss, and reduced their illness uncertainty. Perceived
      understanding of illness was negatively related to the level of illness
      uncertainty. The stimuli frame of uncertainty acted as a mediator between the
      intervention and the uncertainty. The intervention increased the level of
      cognition of the stimuli frame of uncertainty and then indirectly lowered the
      uncertainty level. CONCLUSIONS/IMPLICATIONS: These findings support the
      effectiveness of the individual health education strategy with the information
      sheet in delivering to patients critical information about their condition and
      treatment. Moreover, this intervention may effectively increase illness cognition
      and reduce uncertainty in patients with sudden hearing loss. Clinical nurse
      staffs may use the findings of this study to improve their health education
      efficacy.

PMID- 24899558
TI  - [The use of OSCE to evaluate the competency of discharge nurses].
AB  - BACKGROUND: Clear directions and explanations from nurses related to health
      behaviors and discharge procedures have been shown to effectively reduce the risk
      of patient readmission. Nurses thus need to develop good communication skills in
      order to ensure that their communications help patients become better-informed
      and less anxious about discharge procedures. PURPOSE: This research evaluates the
      communication skills of nurses following two different education interventions.
      METHODS: Experimental design principles for education interventions were followed
      in this research. Medical nurses certified at the N to N2 level in a municipal
      hospital in Taipei City were enrolled as participants (N=78) and divided into an
      experimental group and control group using stratified purposive randomization.
      The experimental group received clinical scenario-based simulation education for
      communication. The control group received standard class-based education for
      communication. Both groups received a pre-test evaluation and an OSCE post-test
      evaluation. Results were analyzed using SPSS 17.0 software. RESULTS: Independent
      t-test results revealed significant increases in communication skills (t=3.406,
      p<.05) in both groups, with the increase in the experimental group (M=5.00,
      SD=0.82) significantly greater than the increase in the control group (M=4.11,
      SD=1.41). However, the mean scores from the post-test standardized patient survey
      found no significant differences between the two groups in terms of communication
      skills. CONCLUSIONS: The results indicate that the clinical scenario-based
      simulation education intervention is more effective than traditional class-based
      education in enhancing the communication skills of nurses.

PMID- 24899559
TI  - [Nursing workplace bullying and turnover intention: an exploration of associated
      factors at a medical center in Southern Taiwan].
AB  - BACKGROUND: The chronic shortage of nursing staffs in hospitals continues to
      increasingly and negatively impact the ability of medical care systems to deliver
      effective care and ensure the safety of patients. Bullying is one factor known to
      exacerbate turnover in the nursing workplace. PURPOSE: This study explores
      workplace bullying and turnover intention among nurses working at a medical
      center in Southern Taiwan. METHODS: A cross-sectional and correlation research
      design was conducted using the Negative Acts Questionnaire-Revised (NAQ-R) and
      the Turnover Intention Questionnaire. A convenience, purposive sample of 708
      nurses was recruited. Inclusion criteria included: holding an RN license, able to
      communicate in both Mandarin and Hokkienese, >6 months of clinical experience,
      and an NAQ-R score higher than 23. Data were analyzed using SPSS19.0 software.
      RESULTS: Approximately 85% of participants had experienced some degree of
      workplace bullying during the previous 6-month period. The trend of the turnover
      intention tended to the right at a high degree. A moderate, positive, and
      significant correlation was found between turnover intention and bullying total
      scores (r=.39, p<.05). Multiple regression showed bullying as the most important
      predicator of turnover intention (15.10%). CONCLUSIONS/IMPLICATIONS FOR PRACTICE:
      Based on our findings, we suggest that nurses should enhance their awareness of
      the negative consequences of workplace bullying. Furthermore, hospitals should
      implement appropriate mechanisms to decrease the phenomenon of inter-staff
      bullying, improve the nursing workplace environment, and reduce the rate of
      turnover intention.

PMID- 24899560
TI  - [The impact of nurse-led case management on the quality of HIV care].
AB  - BACKGROUND: Monitoring the quality of human immunodeficiency virus (HIV) care and
      evaluating the effectiveness of HIV case management programs (CMPs) as approaches
      to raising the rate of HIV care retention and to improving the efficacy of viral
      suppression after the initiation of highly active antiretroviral therapy (HAART)
      are important focuses of research worldwide. PURPOSE: This study describes the
      trends and evaluates the influence of CMPs on retention in care and viral
      suppression among patients in Taiwan diagnosed with HIV from 2008 to 2010.
      METHODS: This retrospective study enrolled 1,302 HIV-positive individuals who had
      visited at least one outpatient clinic between 2008 and 2012. Of these patients,
      715 (54.9%) were enrolled in an HIV CMP. Trend analysis and logistic regression
      were applied to investigate longitudinal trends and the impact of CMPs on the
      quality of HIV care. RESULTS: Retention in care improved substantially from 44.5%
      in 2008 to 57.3% in 2012. The percentage of viral suppression within 12 months of
      the initiation of HAART increased from 88.4% in 2008 to 93.5% in 2012. Of the
      patients who were in HIV CMPs, 73.6% were retained in care, which was
      significantly higher than the 31.7% among those who were not enrolled in CMPs
      (p<.001). Among the patients who received HAART for more than 180 days, those who
      achieved viral suppression within 12 months were significantly more likely to be
      retained in care (adjusted odds ratio=5.36, 95% CI=2.6-10.9, p<.001). CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: Nurse-led case management programs play a role in
      improving HIV-related health outcomes. HIV CMPs are beneficial to HIV-infected
      patients by improving retention in care and are indirectly associated with
      successful viral suppression.

PMID- 24899561
TI  - [A project to improve the completion rate of discharge-planning services for
      organ-transplant patients].
AB  - BACKGROUND & PROBLEMS: The average score for satisfaction with self-care
      instructions among transplant patients was 84 out of 100 in a 2010 survey of
      patient satisfaction with discharge-planning services. This score was
      significantly below the hospital average of 90. In addition, discharged patients
      made more frequent telephone inquiries to healthcare providers to ask questions
      about post-organ-transplantation self-care. A follow-up study targeted a sample
      of 30 discharged transplantation patients using hospital medical record reviews
      and telephone inquiries. This survey found a transplant instruction completion
      rate of 75% during discharge preparation and 69% accuracy among participants in
      answering self-care knowledge questions. Both figures were lower than expected.
      PURPOSE: The goal of this project was to increase the instruction completion rate
      from 75% to 100% and the percentage of correct answers to self-care knowledge
      questions self-care knowledge from 69% to 95%. RESOLUTIONS: This study integrated
      all relevant nursing information into a standardized discharge-planning service
      booklet that was given to inpatients for reference. Furthermore, a self-care
      checklist was developed and introduced. Finally, a standard procedure for
      delivering nursing instructions and a regular audit and follow-up monitoring
      system were established. RESULTS: The nurses' instruction completion rate rose to
      100% and the percentage of questions on self-care knowledge correctly answered by
      patients increased to 98%. CONCLUSIONS: Adopting a patient-centered philosophy of
      care and a model of interdisciplinary collaboration effectively integrated
      resources and promotes nursing quality and quality of life for transplant
      patients. The project effectively improved the completing rate for post
      transplant discharge-planning service instructions and enhanced the self-care
      knowledge of transplant patients.

PMID- 24899562
TI  - [The effect of bundle care on central line associated bloodstream infection in a
      medical intensive care unit].
AB  - BACKGROUND & PROBLEMS: While the central line catheter is a common device used in
      intensive medical care, it is a frequent source of nosocomial infection. The
      central line associated bloodstream infection (CLABSI) rate at our medical ICU
      had increased steadily, with an average rate between January and May 2011 of
      .47%. We used a cross-team approach to implement bundle care as a strategy to
      reduce the CLABSI rate. PURPOSE: We designed a project to reduce the CLABSI rate
      below .3% in our ICU. RESOLUTION: This project was conducted between June 2011
      and May 2012. Our strategy included providing a sterile towel, implementing
      maximal barrier precautions (head to toe), designing an illustration explaining
      how to use 2% CHG, establishing a procedures and care checklist, implementing
      quality assurance for procedures and care, and providing education on bundle
      care. RESULTS: The CLABSI rate reduced to .24% after project implementation. This
      result was below the target of .30%. CONCLUSIONS: We want to share this
      experience to help other hospitals and units improve critical care quality and to
      continue working to achieve a zero-tolerance infection rate.

PMID- 24899563
TI  - [Polypharmacy issues in older adults].
AB  - Polypharmacy is a major concern in the care of older adults. People over 65 years
      of age frequently have multiple medical conditions and may have cancer, which
      requires multiple medications for treatment. The use of multiple medications
      increases the risk of drug-drug interactions, non-adherence, and adverse drug
      reactions. Polypharmacy is a term that refers to a high number of prescribed
      medications, usually five and above, or the use of more medications than is
      clinically justified. Although medications are an important factor in improving
      and maintaining the quality of life of older adults, polypharmacy increases the
      risks of morbidity and mortality, loss of functional independence, and a
      multiplicity of cognitive and physical problems in this population. This article
      examines issues related to polypharmacy in older adults and identifies nursing
      strategies and interventions to detect and prevent polypharmacy. Nursing
      strategies discussed include: (1) increasing patient knowledge of pharmacological
      issues, (2) increasing patient medication management competency, (3) promoting
      safe patient medication practices, and (4) enhancing patient education. Nurses
      must be familiar with medicine regimens, understand the primary factors that
      affect adherence, and participate in continuing education to enhance their
      ability to safeguard older adult patients. 

PMID- 24899564
TI  - [A comparison of convenience sampling and purposive sampling].
AB  - Convenience sampling and purposive sampling are two different sampling methods.
      This article first explains sampling terms such as target population, accessible
      population, simple random sampling, intended sample, actual sample, and
      statistical power analysis. These terms are then used to explain the difference
      between "convenience sampling" and purposive sampling." Convenience sampling is a
      non-probabilistic sampling technique applicable to qualitative or quantitative
      studies, although it is most frequently used in quantitative studies. In
      convenience samples, subjects more readily accessible to the researcher are more
      likely to be included. Thus, in quantitative studies, opportunity to participate
      is not equal for all qualified individuals in the target population and study
      results are not necessarily generalizable to this population. As in all
      quantitative studies, increasing the sample size increases the statistical power
      of the convenience sample. In contrast, purposive sampling is typically used in
      qualitative studies. Researchers who use this technique carefully select subjects
      based on study purpose with the expectation that each participant will provide
      unique and rich information of value to the study. As a result, members of the
      accessible population are not interchangeable and sample size is determined by
      data saturation not by statistical power analysis.

PMID- 24899565
TI  - [Concept analysis of medication adherence in patients with chronic disease].
AB  - Pharmacotherapy plays an important role in the management of chronic diseases.
      However, many patients with chronic disease do not adhere to their medication
      regimen. This results in worsening symptoms and frequent re-hospitalizations. As
      a result, healthcare providers may view these patients as bad. Medication
      adherence is a complex concept. Analyzing this concept may assist nurses to
      improve patient-centered care. This paper uses Walker & Avant's method to conduct
      a concept analysis of medication adherence. Results show the defining attributes
      of medication adherence as: (1) knowing and agreeing to the medication; (2)
      communicating and negotiating the regimen; and (3) active, continuous involvement
      in and appraisal of the treatment effect. Identified antecedents of medication
      adherence included the patient having: (1) a prescribed medication regimen; (2)
      cognitive and action abilities in her / his role as a patient; and (3) level of
      preparation for medication treatment. Identified consequences of medication
      adherence include: (1) improving symptom control; (2) decreasing re
      hospitalizations and mortality; (3) reducing medical care costs; (4) restoring
      self-esteem; and (5) diminishing depression. It is hoped that this concept
      analysis provides a reference for nurses to achieve a better understanding of
      medication adherence and further improve nursing practice. 

PMID- 24899567
TI  - On-surface Ullmann polymerization via intermediate organometallic networks on
      Ag(111).
AB  - The role of organometallic intermediates during on-surface polymerization via
      Ullmann coupling was studied on Ag(111). The polymerization progress was
      monitored by X-ray photoelectron spectroscopy (XPS). Scanning Tunneling
      Microscopy (STM) was used to characterize organometallic and covalent networks
      and to identify the temperature regimes for organometallic and covalent bond
      formation. 

PMID- 24899566
TI  - Morphological, genetic and molecular characteristics of barley root hair mutants.
AB  - Root hairs are tubular outgrowths of specialized epidermal cells called
      trichoblasts. They affect anchoring plants in soil, the uptake of water and
      nutrients and are the sites of the interaction between plants and microorganisms.
      Nineteen root hair mutants of barley representing different stages of root hair
      development were subjected to detailed morphological and genetic analyses. Each
      mutant was monogenic and recessive. An allelism test revealed that nine loci were
      responsible for the mutated root hair phenotypes in the collection and 1-4
      mutated allelic forms were identified at each locus. Genetic relationships
      between the genes responsible for different stages of root hair formation were
      established. The linkage groups of four loci rhl1, rhp1, rhi1 and rhs1, which had
      previously been mapped on chromosomes 7H, 1H, 6H and 5H, respectively, were
      enriched with new markers that flank the genes at a distance of 0.16 cM to 4.6
      cM. The chromosomal position of three new genes - two that are responsible for
      the development of short root hairs (rhs2 and rhs3) and the gene that controls an
      irregular root hair pattern (rhi2) - were mapped on chromosomes 6H, 2H and 1H,
      respectively. A comparative analysis of the agrobotanical parameters between some
      mutants and their respective parental lines showed that mutations in genes
      responsible for root hair development had no effect on the agrobotanical
      performance of plants that were grown under controlled conditions. The presented
      mutant collection is a valuable tool for further identification of genes
      controlling root hair development in barley.

PMID- 24899569
TI  - Identification of the metabolites of gigantol in rat urine by ultra-performance
      liquid chromatography combined with electrospray ionization quadrupole time-of
      flight tandem mass spectrometry.
AB  - Gigantol is a typical bibenzyl compound isolated from Dendrobii Caulis that has
      been widely used as a medicinal herb in China for the treatment of diabetic
      cataract, cancer and arteriosclerosis obliterans and as a tonic for stomach
      nourishment, saliva secretion promotion and fever reduction. However, few studies
      have been carried out on its in vivo metabolism. In the present study, a rapid
      and sensitive method based on ultra-performance liquid
      chromatography/electrospray ionization quadrupole time-of-flight tandem mass
      spectrometry (UPLC-Q/TOF-MS) in positive ion mode was developed and applied to
      identify the metabolites of gigantol in rat urine after a single oral dose (100
      mg/kg). Chromatographic separation was performed on an Acquity UPLC HSS T3 column
      (100 * 2.1 mm i. d., 1.8 um) using acetonitrile and 0.1% aqueous formic acid as
      mobile phases. A total of 11 metabolites were detected and identified as all
      phase II metabolites. The structures of the metabolites were identified based on
      the characteristics of their MS, MS(2) data and chromatographic retention times.
      The results showed that glucuronidation is the principal metabolic pathway of
      gigantol in rats. The newly identified metabolites are useful to understand the
      mechanism of elimination of gigantol and, in turn, its effectiveness and
      toxicity. As far as we know, this is the first attempt to investigate the
      metabolic fate of gigantol in vivo.

PMID- 24899568
TI  - Genomic mapping of phosphorothioates reveals partial modification of short
      consensus sequences.
AB  - Bacterial phosphorothioate (PT) DNA modifications are incorporated by Dnd
      proteins A-E and often function with DndF-H as a restriction-modification (R-M)
      system, as in Escherichia coli B7A. However, bacteria such as Vibrio
      cyclitrophicus FF75 lack dndF-H, which points to other PT functions. Here we
      report two novel, orthogonal technologies to map PTs across the genomes of B7A
      and FF75 with >90% agreement: single molecule, real-time sequencing and deep
      sequencing of iodine-induced cleavage at PT (ICDS). In B7A, we detect PT on both
      strands of GpsAAC/GpsTTC motifs, but with only 12% of 40,701 possible sites
      modified. In contrast, PT in FF75 occurs as a single-strand modification at
      CpsCA, again with only 14% of 160,541 sites modified. Single-molecule analysis
      indicates that modification could be partial at any particular genomic site even
      with active restriction by DndF-H, with direct interaction of modification
      proteins with GAAC/GTTC sites demonstrated with oligonucleotides. These results
      point to highly unusual target selection by PT-modification proteins and rule out
      known R-M mechanisms. 

PMID- 24899570
TI  - The effects of an oral preparation containing hyaluronic acid (Oralvisc(r)) on
      obese knee osteoarthritis patients determined by pain, function, bradykinin,
      leptin, inflammatory cytokines, and heavy water analyses.
AB  - The purpose of this study was to determine the effects of an oral preparation
      containing hyaluronic acid on osteoarthritic knee joint pain and function as well
      as changes in inflammatory cytokines, bradykinin, and leptin. We also used heavy
      water to determine the turnover rates of glycosaminoglycans in synovial fluid.
      This was a double-blind, randomized, placebo-controlled study of 40 subjects over
      a period of 3 months. Visual analog scale, Western Ontario McMaster pain, and
      WOMAC function scores were recorded. Serum and synovial fluid were measured by
      enzyme-linked immunosorbent assays for inflammatory cytokines, bradykinin, and
      leptin. In 20 subjects, terminal heavy water ingestion was used for spectral
      analyses of serum and joint fluid samples. There were statistically significant
      improvements in pain and function. Both serum and synovial fluid samples showed
      significant decreases for a majority of inflammatory cytokines, leptin, and
      bradykinin in the oral hyaluronic acid preparation group. Heavy water analyses
      revealed a significant decrease in hyaluronic acid turnover in the synovial fluid
      of the treatment group. A preparation containing hyaluronic acid and other
      glycosaminoglycans holds promise for a safe and effective agent for the treatment
      for patients with knee osteoarthritis and who are overweight. Further studies
      will be required to see whether this is a disease-modifying agent.

PMID- 24899571
TI  - Identification of lymphoma predictors in patients with primary Sjogren's
      syndrome: a systematic literature review and meta-analysis.
AB  - To identify risk and predictors of lymphoma or lymphoproliferative disease in
      patients with primary Sjogren syndrome. Articles were identified through a
      comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies
      had to investigate primary Sjogren syndrome patients, 18 years of age or older,
      with the goal of examining potential clinical, immunological and hematological
      risk factors for lymphoma or lymphoproliferative disease. The quality of the
      studies was graded using the Oxford Levels of Evidence Scale. Whenever possible,
      the authors created evidence tables and performed meta-analysis. Of 900 studies
      identified, 18 were selected for inclusion. These studies provided data from over
      15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement,
      palpable purpura, low C4 serum levels and cryoglobulins were the most consistent
      non-Hodgkin's lymphoma/lymphoproliferative disease predictors. Additionally, some
      of the studies identified splenomegaly, low C3 serum levels, lymphopenia and
      neutropenia as significant prognostic factors. The detection of germinal center
      like lesions in primary Sjogren Syndrome diagnostic salivary biopsies was also
      proposed as highly predictive of non-Hodgkin's lymphoma. In contrast, anemia,
      anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and
      hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative
      disease. Patients with primary Sjogren syndrome have an increased risk of
      lymphoma or lymphoproliferative disease compared to the general population.
      Ascertaining relevant and reliable predictors in this patient population would
      greatly facilitate the identification of patients at elevated risk for closer
      monitoring in the context of limited resources.

PMID- 24899572
TI  - New elements in the C-type natriuretic peptide signaling pathway inhibiting swine
      in vitro oocyte meiotic resumption.
AB  - C-type natriuretic peptide (CNP) and its cognate receptor, natriuretic peptide
      receptor (NPR) B, have been shown to promote cGMP production in granulosa/cumulus
      cells. Once transferred to the oocyte through the gap junctions, the cGMP
      inhibits oocyte meiotic resumption. CNP has been shown to bind another
      natriuretic receptor, NPR-C. NPR-C is known to interact with and degrade bound
      CNP, and has been reported to possess signaling functions. Therefore, NPR-C could
      participate in the control of oocyte maturation during swine in vitro maturation
      (IVM). Here, we examine the effect of CNP signaling on meiotic resumption, the
      amount of cGMP and gap junctional communication (GJC) regulation during swine
      IVM. The results show an inhibitory effect of CNP in inhibiting oocyte meiotic
      resumption in follicle-stimulating hormone (FSH)-stimulated IVM. We also found
      that an NPR-C-specific agonist (cANP([4-23])) is likely to play a role in
      maintaining meiotic arrest during porcine IVM when in the presence of a
      suboptimal dose of CNP. Moreover, we show that, even if CNP can increase
      intracellular concentration of cGMP in cumulus-oocyte complexes, cANP((4-23)) had
      no impact on cGMP concentration, suggesting a potential cGMP-independent
      signaling pathway related to NPR-C activation. These data support a potential
      involvement of cANP((4-23)) through NPR-C in inhibiting oocyte meiotic resumption
      while in the presence of a suboptimal dose of CNP. The regulation of GJC was not
      altered by CNP, cANP((4-23)), or the combination of CNP and cANP((4-23)),
      supporting their potential contribution in sending signals to the oocytes. These
      findings offer promising insights in to new elements of the signaling pathways
      that may be involved in inhibiting resumption of meiosis during FSH-stimulated
      swine IVM. 

PMID- 24899574
TI  - Scaffold subunit Aalpha of PP2A is essential for female meiosis and fertility in
      mice.
AB  - Ppp2r1a encodes the scaffold subunit Aalpha of protein phosphatase 2A (PP2A),
      which is an important and ubiquitously expressed serine threonine phosphatase
      family and plays a critical role in many fundamental cellular processes. To
      identify the physiological role of PP2A in female germ cell meiosis, we
      selectively disrupted Ppp2r1a expression in oocytes by using the Cre-Loxp
      conditional knockout system. Here we report for the first time that oocyte
      specific deletion of Ppp2r1a led to severe female subfertility without affecting
      follicle survival, growth, and ovulation. PP2A-Aalpha was essential for
      regulating oocyte meiotic maturation because depletion of PP2A-Aalpha facilitated
      germinal vesicle breakdown, causing elongation of the MII spindle and precocious
      separation of sister chromatids. The resulting eggs had high risk of aneuploidy,
      though they could be fertilized, leading to defective embryonic development and
      thus subfertility. Our findings provide strong evidence that PP2A-Aalpha within
      the oocyte plays an indispensable role in oocyte meiotic maturation, though it is
      dispensable for folliculogenesis in the mouse ovary. 

PMID- 24899573
TI  - Simultaneous gene deletion of gata4 and gata6 leads to early disruption of
      follicular development and germ cell loss in the murine ovary.
AB  - Granulosa cell formation and subsequent follicular assembly are important for
      ovarian development and function. Two members of the GATA family of transcription
      factors, GATA4 and GATA6, are expressed in ovarian somatic cells early in
      development, and their importance in adult ovarian function has been recently
      highlighted. In this study, we demonstrated that the embryonic loss of Gata4 and
      Gata6 expression within the ovary results in a strong down-regulation of genes
      involved in the ovarian developmental pathway (Fst and Irx3) as well as
      diminished expression of the pregranulosa and granulosa cell markers SPRR2 and
      FOXL2, respectively. Postnatal ovaries deficient in both Gata genes show impaired
      somatic cell proliferation and arrested follicular development at the primordial
      stage, where oocytes are either enclosed by one layer of squamous granulosa cells
      or remain in germ cell nests/clusters. Furthermore, germ cell nests and
      primordial follicles are predominantly localized to the central region of the
      Sf1Cre; Gata4(flox/flox) Gata6(flox/flox) ovaries, where the boundary between the
      medulla and cortex is almost nonexistent. Lastly, most of the oocytes are lost
      early in development in conditional double mutant ovaries, which confirms the
      importance of normally differentiated granulosa cells as supporting cells for
      oocyte survival. Thus, both GATA4 and GATA6 proteins are fundamental regulators
      of granulosa cell differentiation and proliferation, and consequently of proper
      follicular assembly during normal ovarian development and function. 

PMID- 24899575
TI  - Physical and mental development of children after levonorgestrel emergency
      contraception exposure: a follow-up prospective cohort study.
AB  - Levonorgestrel (LNG), a dedicated emergency contraception (EC) product, has been
      available over-the-counter in China for more than 14 yr. Although LNG-EC is
      considered to have no effects on the developing fetus if the contraceptive fails
      and pregnancy occurs, there have been a few studies specifically examining this
      issue. The purpose of this study was to compare the physical and mental
      development of children born after LNG-EC failure with that of a cohort of
      children born to mothers with no history of exposure to LNG or any teratogenic
      substances. A group of 195 children who were exposed to LNG-EC during their
      mothers' conception cycle (study group) were matched to a group of 214 children
      without exposure to LNG (control group). The physical and mental development of
      the children were evaluated and compared over a 2-yr period. There were four
      congenital malformations in the study group and three in the control group (2.1%
      vs. 1.4%, respectively, P > 0.05). Over the 2-yr follow-up period, there were no
      statistically significant differences between the two groups with respect to
      children's weight, height, head circumference, and intelligence scores, and the
      values of all parameters of both groups were similar to those of the national
      standards. In summary, LNG-EC has no effect on the physical growth, mental
      development, or occurrence of birth defects in children born from pregnancies in
      which EC failed. 

PMID- 24899577
TI  - Adrenomedullin increases the short-circuit current in the mouse seminal vesicle:
      actions on chloride secretion.
AB  - Adrenomedullin (ADM) may regulate seminal vesicle fluid secretion, and this may
      affect sperm quality. In this study, we investigated the effect of ADM on
      chloride secretion in the mouse seminal vesicle. The presence of ADM in mouse
      seminal vesicle was confirmed using immunostaining, and the molecular species was
      determined using gel filtration chromatography coupled with enzyme-linked assay
      for ADM. The effects of ADM on chloride secretion were studied by short-circuit
      current technique in a whole-mount preparation of mouse seminal vesicle in an
      Ussing chamber. The effects of specific ADM and calcitonin gene-related peptide
      (CGRP) receptor antagonists were investigated. Whether the ADM effect depended on
      the cAMP- and/or calcium-activated chloride channel was also studied using
      specific chloride channel blockers. The results showed that ADM was present in
      seminal vesicle epithelial cells. The major molecular species was precursor in
      the mouse seminal vesicle. ADM increased short-circuit current through the
      calcium-activated chloride channel in mouse seminal vesicle, and CGRP receptor
      was involved. We conclude that ADM may regulate chloride and fluid secretion from
      the seminal vesicle, which may affect the composition of the seminal plasma
      bathing the sperm and, hence, fertility. 

PMID- 24899578
TI  - The nuclear receptor NR2F2 activates star expression and steroidogenesis in mouse
      MA-10 and MLTC-1 Leydig cells.
AB  - Testosterone production is dependent on cholesterol transport within the
      mitochondrial matrix, an essential step mediated by a protein complex containing
      the steroidogenic acute regulatory (STAR) protein. In steroidogenic Leydig cells,
      Star expression is hormonally regulated and involves several transcription
      factors. NR2F2 (COUP-TFII) is an orphan nuclear receptor that plays critical
      roles in cell differentiation and lineage determination. Conditional NR2F2
      knockout prior to puberty leads to male infertility due to insufficient
      testosterone production, suggesting that NR2F2 could positively regulate
      steroidogenesis and Star expression. In this study we found that NR2F2 is
      expressed in the nucleus of some peritubular myoid cells and in interstitial
      cells, mainly in steroidogenically active adult Leydig cells. In MA-10 and MLTC-1
      Leydig cells, small interfering RNA (siRNA)-mediated NR2F2 knockdown reduces
      basal steroid production without affecting hormone responsiveness. Consistent
      with this, we found that STAR mRNA and protein levels were reduced in NR2F2
      depleted MA-10 and MLTC-1 cells. Transient transfections of Leydig cells revealed
      that a -986 bp mouse Star promoter construct was activated 3-fold by NR2F2. Using
      5' progressive deletion constructs, we mapped the NR2F2-responsive element
      between -131 and -95 bp. This proximal promoter region contains a previously
      uncharacterized direct repeat 1 (DR1)-like element to which NR2F2 is recruited
      and directly binds. Mutations in the DR1-like element that prevent NR2F2 binding
      severely blunted NR2F2-mediated Star promoter activation. These data identify an
      essential role for the nuclear receptor NR2F2 as a direct activator of Star gene
      expression in Leydig cells, and thus in the control of steroid hormone
      biosynthesis. 

PMID- 24899576
TI  - Engineered nanomaterials: an emerging class of novel endocrine disruptors.
AB  - Over the past decade, engineered nanomaterials (ENMs) have garnered great
      attention for their potentially beneficial applications in medicine, industry,
      and consumer products due to their advantageous physicochemical properties and
      inherent size. However, studies have shown that these sophisticated molecules can
      initiate toxicity at the subcellular, cellular, and/or tissue/organ level in
      diverse experimental models. Investigators have also demonstrated that, upon
      exposure to ENMs, the physicochemical properties that are exploited for public
      benefit may mediate adverse endocrine-disrupting effects on several endpoints of
      mammalian reproductive physiology (e.g., steroidogenesis, spermatogenesis,
      pregnancy). Elucidating these complex interactions within reproductive cells and
      tissues will significantly advance our understanding of ENMs as an emerging class
      of novel endocrine disruptors and reproductive toxicants. Herein we reviewed the
      recent developments in reproductive nanotoxicology and identified the gaps in our
      knowledge that may serve as future research directions to foster continued
      advancement in this evolving field of study. 

PMID- 24899579
TI  - Optimal ablation volumes are achieved at submaximal power settings in a 2.45-GHz
      microwave ablation system.
AB  - INTRODUCTION: Local ablative therapies, including microwave ablation (MWA), are
      common treatment modalities for in situ tumor destruction. Currently, 2.45-GHz
      ablation systems are gaining prominence because of the shorter application times
      required. The aims of this study were to determine optimal power and time to
      ablation volume (AbV) ratios for a new 1.8-mm-2.45-GHz antenna using ex vivo
      tissue models. METHODS: The 1.8-mm-2.45-GHz Accu2i MWA system was employed to
      perform ablations in bovine liver, porcine muscle, and porcine kidney ex vivo.
      Whole tissues were prewarmed (35 degrees C) and multiple ablations performed at
      power settings of 60 to 180 W for 2- to 6-minute time intervals. Postablation,
      tissues were dissected, AbVs calculated, and correlations to power and time
      settings made. RESULTS: Significant increases in AbV were measured between each
      of the time points for a constant power setting in all 3 tissues. Increasing
      power settings led to significant increases in AbV at power settings <=140 W.
      However, no significant increase in AbV was obtained at power settings >140 W.
      CONCLUSIONS: Optimal efficiency for MWA using a new 1.8-mm-2.45-GHz system is
      achieved at settings of <=140 W for 6 minutes in a range of ex vivo tissue and no
      additional benefit occurs by increasing the power setting to 180 W in these
      tissues.

PMID- 24899580
TI  - Young and uninsured: Insurance patterns of recently diagnosed adolescent and
      young adult cancer survivors in the AYA HOPE study.
AB  - BACKGROUND: Young adults have historically been the least likely to have health
      insurance in the United States. Previous studies of survivors of childhood cancer
      found lower rates of insurance and less access to medical care compared with
      siblings; however, to the authors' knowledge, no studies to date have examined
      continuity of insurance after a cancer diagnosis in adolescents and young adults
      (AYAs). METHODS: Using the AYA Health Outcomes and Patient Experience study, a
      cohort of 465 individuals aged 15 to 39 years from participating Surveillance,
      Epidemiology, and End Results registries, we evaluated changes in and sponsors of
      health insurance coverage after diagnosis, coverage of physician-recommended
      tests, and factors associated with lack of insurance after a cancer diagnosis
      using chi-square tests and multivariable logistic regression. RESULTS: Greater
      than 25% of AYA survivors of cancer (118 survivors) experienced some period
      without insurance up to 35 months after diagnosis. Insurance rates were high in
      the initial year after diagnosis (6 months-14 months; 93.3%) but decreased
      substantially at follow-up (15 months-35 months; 85.2%). The most common sponsor
      of health insurance was employer/school coverage (43.7%). Multivariable analysis
      indicated that older survivors (those aged 25-39 years vs 15-19 years; odds
      ratio, 3.35 [P < .01]) and those with less education (high school or less vs
      college graduate; odds ratio, 2.80 [P < .01]) were more likely to experience a
      period without insurance after diagnosis. Furthermore, > 20% of survivors
      indicated there were physician-recommended tests/treatments that were not covered
      by insurance, but > 80% received them regardless of coverage. CONCLUSIONS:
      Insurance rates appear to decrease with time since diagnosis in AYA survivors of
      cancer. Future studies should examine how new policies under the Patient
      Protection and Affordable Care Act extend access and insurance coverage beyond
      initial treatment.

PMID- 24899582
TI  - Disclosure Suspicion Bias and Abuse Disclosure: Comparisons Between Sexual and
      Physical Abuse.
AB  - Prior research has found that children disclosing physical abuse appear more
      reticent and less consistent than children disclosing sexual abuse. Although this
      has been attributed to differences in reluctance, it may also be due to
      differences in the process by which abuse is suspected and investigated.
      Disclosure may play a larger role in arousing suspicions of sexual abuse, while
      other evidence may play a larger role in arousing suspicions of physical abuse.
      As a result, children who disclose physical abuse in formal investigations may be
      doing so for the first time, and they may be more reluctant to provide details of
      the abuse. We examined abuse disclosure and evidence in comparable samples of
      court-substantiated physical (n = 33) and sexual (n = 28) abuse. Consistent with
      predictions, the likelihood that the child had disclosed abuse before an
      investigation began was lower in physical (27%) than that in sexual (67%) abuse
      cases, and there was more nondisclosure evidence of abuse in physical abuse
      cases. These findings have implications for understanding the dynamics and
      meaning of disclosure in cases involving different types of abuse.

PMID- 24899583
TI  - [2]Pseudorotaxane formation between rigid Y-shaped 2,4,5-triphenylimidazolium
      axles and [24]crown-8 ether wheels.
AB  - A new templating motif for the formation of [2]pseudorotaxanes is described in
      which rigid, Y-shaped axles with an imidazolium core and aromatic substituents at
      the 2-, 4- and 5-positions interact with [24]crown-8 ether wheels ([24]crown-8
      and dibenzo[24]crown-8). The Y-shape of the axle significantly enhances the
      association between axle and wheel when compared to simple imidazolium cations. 

PMID- 24899584
TI  - Comparative electrostatic force microscopy of tetra- and intra-molecular G4-DNA.
AB  - Two forms of G4-DNA, with parallel and pairwise anti-parallel strands, are
      studied using atomic force microscopy. The directionality of the strands affects
      the molecules' structural properties (different height and length) and their
      electrical polarizability. Parallel G4-DNA is twice as polarizable as anti
      parallel G4-DNA, suggesting it is a better electrical wire for bio
      nanoelectronics. 

PMID- 24899585
TI  - Carnelley's rule and the prediction of melting point.
AB  - Carnelley (1882) made some important and useful observations on the relationship
      between the arrangement of the atoms in a molecule and its melting point.
      According to Brown and Brown (2000. J Chem Ed 77:724-731), Carnelley's rule
      states "of two or more isometric compounds, those whose atoms are the more
      symmetrically and the more compactly arranged melt higher than those in which the
      atomic arrangement is asymmetrical or in the form of long chains." Carnelley's
      rule can best be understood and quantitated from the dependence of the entropy of
      melting upon molecular geometry.

PMID- 24899586
TI  - A Systematic Review of Post-traumatic Stress Disorder and Depression Amongst
      Iraqi Refugees Located in Western Countries.
AB  - A systematic review of literature reporting prevalence rates of posttraumatic
      stress disorder (PTSD) and depression amongst community samples of resettled
      Iraqi refugees was undertaken. A search of the electronic databases of Medline,
      PsychINFO, CINAHL, PILOTS, Scopus, and Cochrane, up to November 2013 was
      conducted. Following the application of the inclusion and exclusion criteria,
      eight empirical papers were included in the review and analysis. Specifically,
      six studies reported on PTSD prevalence (total n = 1,912), which ranged from 8 to
      37.2 % and seven studies reported on rates of depression (total n = 1,647) noted
      to be 28.3 to 75 %. The overall interobserver agreement for the methodological
      quality assessment was good to excellent with a Kappa coefficient of 0.64. Iraqi
      refugees continue to represent one of the largest groups being resettled
      worldwide. This systematic review indicates that prevalence of PTSD and
      depression is high and should be taken into consideration when developing mental
      health early intervention and treatment services. 

PMID- 24899581
TI  - Aberrant regulation of FBW7 in cancer.
AB  - FBW7 (F-box and WD repeat domain-containing 7) or Fbxw7 is a tumor suppressor,
      which promotes the ubiquitination and subsequent degradation of numerous
      oncoproteins including Mcl-1, Cyclin E, Notch, c- Jun, and c-Myc. In turn, FBW7
      is regulated by multiple upstream factors including p53, C/EBP-delta, EBP2, Pin1,
      Hes-5 and Numb4 as well as by microRNAs such as miR-223, miR-27a, miR-25, and miR
      129-5p. Given that the Fbw7 tumor suppressor is frequently inactivated or deleted
      in various human cancers, targeting FBW7 regulators is a promising anti-cancer
      therapeutic strategy. 

PMID- 24899587
TI  - Technical advance: live-imaging analysis of human dendritic cell migrating
      behavior under the influence of immune-stimulating reagents in an organotypic
      model of lung.
AB  - This manuscript describes technical advances allowing manipulation and
      quantitative analyses of human DC migratory behavior in lung epithelial tissue.
      DCs are hematopoietic cells essential for the maintenance of tissue homeostasis
      and the induction of tissue-specific immune responses. Important functions
      include cytokine production and migration in response to infection for the
      induction of proper immune responses. To design appropriate strategies to exploit
      human DC functional properties in lung tissue for the purpose of clinical
      evaluation, e.g., candidate vaccination and immunotherapy strategies, we have
      developed a live-imaging assay based on our previously described organotypic
      model of the human lung. This assay allows provocations and subsequent
      quantitative investigations of DC functional properties under conditions
      mimicking morphological and functional features of the in vivo parental tissue.
      We present protocols to set up and prepare tissue models for 4D (x, y, z, time)
      fluorescence-imaging analysis that allow spatial and temporal studies of human
      DCs in live epithelial tissue, followed by flow cytometry analysis of DCs
      retrieved from digested tissue models. This model system can be useful for
      elucidating incompletely defined pathways controlling DC functional responses to
      infection and inflammation in lung epithelial tissue, as well as the efficacy of
      locally administered candidate interventions. 

PMID- 24899589
TI  - Sub-xyphoid pleural drain as a determinant of functional capacity and clinical
      results after off-pump coronary artery bypass surgery: a randomized clinical
      trial.
AB  - OBJECTIVES: The aim of this trial was to compare functional capacity, pulmonary
      shunt fraction and clinical outcomes between patients undergoing pleurotomy with
      a pleural drain inserted in the sub-xyphoid position and patients with a pleural
      drain placed in the intercostal position after off-pump coronary artery bypass
      surgery. METHODS: Patients were randomized into two groups according to the
      pleural drain site: Group II (n = 33 intercostal pleural drain); and Group SI (n
      = 35 sub-xyphoid pleural drain). Functional capacity was assessed by the distance
      covered on the 6-min walking test performed preoperatively and on postoperative
      day (POD) 5; in addition, pulmonary function test was determined preoperatively
      and on POD 1 and 5. Pulmonary shunt fraction was evaluated preoperatively and on
      POD 1, and clinical outcomes were recorded throughout the study. RESULTS: Group
      SI had better preservation of lung volumes and capacities in POD compared with
      Group II (P <0.05). Pulmonary shunt fraction increased in both groups
      postoperatively; however, Group SI showed a smaller pulmonary shunt fraction
      (0.26 +/- 0.04 vs 0.21 +/- 0.04%; P = 0.0014). Functional capacity was
      significantly reduced in both groups on POD 5; however, Group SI showed better
      preservation of functional capacity (P = 0.0001). Group SI had better
      postoperative clinical results, with lower incidence of atelectasis and pleural
      effusion (P <0.05), lower pain scores (P <0.0001), and shorter orotracheal
      intubation and hospitalization lengths (P <0.001). CONCLUSIONS: Sub-xyphoid
      pleural drain determined better functional capacity and exercise tolerance with a
      smaller pulmonary shunt fraction and improved clinical outcomes compared with
      intercostal pleural drainage after off-pump coronary artery bypass surgery.

PMID- 24899590
TI  - Is it possible to predict the risk of ischaemic bowel after cardiac surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'Is it possible to predict the risk of
      ischaemic bowel after cardiac surgery?' Altogether 80 papers were found as a
      result of the reported search, of which 7 represented the best evidence to answer
      the clinical question. The authors, journal, date and country of publication,
      patient group studied, study type, relevant outcomes and results of these papers
      are tabulated. This best evidence topic presents 68 214 cardiac surgical patients
      from seven major cardiothoracic centres dated from 1980 to 2011. The incidence
      and mortality rates of bowel ischaemia after cardiac surgery range from 0.07-0.5
      and 59-64%, respectively. Advanced age and peripheral vascular disease are the
      common preoperative risk factors, which were reported by 3 papers each. The most
      common intraoperative risk factors were prolonged cross-clamp and cardiopulmonary
      bypass time, which were reported by 3 papers each. Five of 7 papers reported that
      the use of intra-aortic balloon pump was a significant risk factor. The use of
      inotropes, postoperative blood loss and postoperative renal failure were reported
      by 3 of 7 papers, each to be a significant risk factor for postoperative bowel
      ischaemia in cardiac surgery patients. We, therefore, conclude that these are
      probably the most significant and useful predictive risk factors for bowel
      ischaemia after cardiac surgery. Thus, careful intraoperative management to
      minimize cardiopulmonary bypass and cross-clamp time and optimal care of
      patients' postoperative haemodynamic status, particularly in elderly patients
      with severe atherosclerotic disease, are useful in preventing this rare but
      lethal postoperative complication. Besides that, a heightened clinical suspicion
      in patients with these risk factors may lead to prompt diagnosis of bowel
      ischaemia, allowing intervention to prevent mortality. The variability of the
      study design and risk factors studied in each paper impose limitation to
      summarize the predicting risk factors. 

PMID- 24899591
TI  - Restoration of optimal left ventricular apical geometry and rotation following
      surgical ventricular restoration using rectangular patch plasty technique: a
      pilot study using cardiac magnetic resonance.
AB  - OBJECTIVES: Clinical outcomes of surgical ventricular restoration (SVR) have been
      confirmed by Registry data. Accurate assessment of left ventricular (LV)
      morphology and function can help optimize these outcomes. METHODS: LV remodelling
      in 7 patients (NYHA class 3 +/- 1.2) with post-myocardial infarction LV aneurysms
      was characterized by the regional LV volume (RLVV) computed by dividing the LV in
      cine steady-state free precession cardiac magnetic resonance imaging (CMR) at
      each slice level into six radial segments. Rotation of the LV apex and base was
      analysed using tagged CMR. The apical conicity ratio was used to characterize the
      restored apical geometry. RESULTS: The mean end-diastolic volume (EDV) was 174.8
      +/- 100.3 ml and the mean ejection fraction (EF) was 18.8 +/- 7.8%. Following
      SVR, all patients had significant clinical improvements (NYHA Class I), and
      significant increases in the left ventricular ejection fraction (LVEF) to 38.8 +/
      4.4%. The LV volumes and regional volumes at the base and apex decreased with a
      trend towards significance. The mean preoperative apical conicity ratio (ACR) was
      1.90 +/- 0.43 and, following SVR by endoventricular linear patch plasty (EVLPP),
      was 1.35 +/- 0.3 (P = 0.02). The percent decrease in the ACR following SVR from
      baseline was 28.68 +/- 10.98%. The apical EF increased from 1.19 +/- 13.9 to 15.8
      +/- 8.2% (P = 0.028). The basal rotations improved from 3.13 +/- 2.1 to 4.69 +/-
      2.94 degrees  (P = 0.04). The apical rotations also improved significantly from
      2.48 +/- 1.23 to 3.93 +/- 2.45 degrees  (P = 0.05) and reversed to the normal
      anticlockwise direction. CONCLUSIONS: SVR by geometric repair using a rectangular
      intracavitary patch helps restoration of a physiological apex with normalization
      of apical rotation reflecting a near-physiological LV function.

PMID- 24899588
TI  - Intracellular immunity: finding the enemy within--how cells recognize and respond
      to intracellular pathogens.
AB  - Historically, once a cell became infected, it was considered to be beyond all
      help. By this stage, the invading pathogen had breached the innate defenses and
      was beyond the reach of the humoral arm of the adaptive immune response. The
      pathogen could still be removed by cell-mediated immunity (e.g., by NK cells or
      cytotoxic T lymphocytes), but these mechanisms necessitated the destruction of
      the infected cell. However, in recent years, it has become increasingly clear
      that many cells possess sensor and effector mechanisms for dealing with
      intracellular pathogens. Most of these mechanisms are not restricted to
      professional immune cells nor do they all necessitate the destruction of the
      host. In this review, we examine the strategies that cells use to detect and
      destroy pathogens once the cell membrane has been penetrated. 

PMID- 24899592
TI  - Successful Bentall procedure in a patient with a Fontan circulation.
AB  - A 33-year old male patient with absent left atrioventricular connection and
      double outlet left ventricle developed severe aortic root dilatation and aortic
      regurgitation. He had undergone initial banding of the pulmonary trunk and atrial
      septectomy, eventually followed by the bidirectional Glenn procedure. At the time
      of the total cavopulmonary connection (at 27 years of age), his ascending aorta
      was plicated and wrapped. Subsequently, the aortic root below the wrapped
      ascending aorta showed further dilatation. The Bentall procedure was successfully
      carried out. 

PMID- 24899593
TI  - Successful operative rib fixation of traumatic flail chest in a patient with
      osteogenesis imperfecta.
AB  - Increasing attention has been directed towards operative rib fixation of
      traumatic flail chest; reported benefits include more rapid weaning from the
      ventilator, decreased intensive care unit stays, decreased complications and
      improved functional results. The outcomes of this surgical intervention in
      patients with osteogenesis imperfecta, a rare condition characterized by low bone
      density and bone fragility, are unknown. This case demonstrates that, in the
      management of traumatic flail chest in a patient with osteogenesis imperfecta,
      surgical fixation can be successful and should be considered early. 

PMID- 24899594
TI  - Lower limb overflow syndrome in extracorporeal membrane oxygenation.
AB  - Peripheral extracorporeal membrane oxygenation (ECMO) is associated with a not
      negligible rate of vascular morbidity. Most vascular complications are related to
      limb ischaemia mainly due to insufficient limb perfusion or embolic events. To
      the best of our knowledge, this is the first report of a severe epidermolysis and
      overflow syndrome as a result of an overperfusion phenomenon through an unknown
      femoral arterio-venous fistula in a patient requiring ECMO support. 

PMID- 24899595
TI  - Thoracoscopic lobectomy after bilateral lung transplantation.
AB  - A 61-year-old female patient with a coin lesion in the right upper lobe was
      referred for surgery. Six years previously she had undergone bilateral lung
      transplantation through bilateral anterior thoracotomies. Computed tomography and
      positron emission tomography of the thorax revealed a 19-mm hypermetabolic lesion
      in the right upper lobe, but no other locoregional or distant disorder. The
      patient underwent wedge resection by video-assisted thoracic surgery (VATS).
      Frozen section revealed a large-cell carcinoma. Subsequently, a VATS right upper
      lobectomy with mediastinal lymph node dissection was performed. Final pathology
      demonstrated a pT1bN0M0 non-small-cell lung cancer of the right upper lobe. One
      year after the operation, the patient was alive and disease free. This case
      report and video illustrate the feasibility of a VATS anatomical resection after
      lung transplantation. 

PMID- 24899596
TI  - Effects of omega-3 fatty acids on tobacco craving in cigarette smokers: A double
      blind, randomized, placebo-controlled pilot study.
AB  - Cigarette smoke induces oxidative stress with subsequent polyunsaturated fatty
      acids (PUFAs) peroxidation. Low concentrations of omega-3 PUFAs can affect
      neurotransmission, resulting in hypofunctioning of the mesocortical systems
      associated with reward and dependence mechanisms and thus may increase cigarette
      craving, hampering smoking cessation efforts. PUFA deficiency, in particular
      eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3),
      has also been linked to reduced psychological health and ability to cope with
      stress. Although stress is well linked to smoking urges and behavior, no research
      to date has examined the effects of PUFA supplementation on tobacco craving. In
      this double-blind, randomized, placebo-controlled pilot study, performed in
      regular cigarette smokers (n=48), administration of 2710 mg EPA/day and 2040 mg
      DHA/day for one month was accompanied by a significant decrease in reported daily
      smoking and in tobacco craving following cigarette cue exposure. Craving did not
      return to baseline values in the month that followed treatment discontinuation.
      This is the first study demonstrating that omega-3 PUFA supplementation reduces
      tobacco craving in regular smokers, compared to placebo treatment. Thus, omega-3
      PUFAs may be of benefit in managing tobacco consumption. Further studies are
      needed on larger samples to explore the possible therapeutic implications for
      heavy cigarette smokers. 

PMID- 24899598
TI  - Role of special pathogenicity versus prevalence theory in pathogenesis of acute
      cystitis caused by Escherichia coli.
AB  - Escherichia coli is the most common pathogen causing acute cystitis in sexually
      active women. Human faeces are generally considered the primary reservoir for
      infection and the faecal-perineal-urethral pathway is the accepted route of
      infection. Two theories have been proposed for the pathogenesis of acute
      cystitis: (1) special pathogenicity, where uropathogenic E. coli (UPEC) encoding
      special virulence factors causes infection; and (2) prevalence, wherein ordinary
      faecal E. coli causes infection by simple mass action. The aim of this study was
      to compare concurrent urinary E. coli isolates from women with acute cystitis
      with their own dominant faecal, vaginal E. coli isolates; thus, these patients
      served as their own control. E. coli isolates from 80 women were analysed by
      phylotyping, virulence profiling (for 15 putative virulence genes) and
      enterobacterial repetitive intergenic consensus (ERIC) PCR. A virulence score was
      calculated for each isolate based on the number of virulence genes detected. Four
      host ecological groups of E. coli were created on the basis of ERIC PCR: group
      UVF, where vaginal and faecal isolates yielded the infecting urine clone; group
      UV, where only vaginal isolates yielded the infecting urine clone; group UF,
      where faecal isolates yielded the infecting urine clone; and group U, where the
      infecting urine clone was distinct. In the majority of cases the infecting E.
      coli clone from urine was also the dominant faecal clone (56.3%; groups UVF and
      UF possessing high virulence scores of 4.6 and 3.9, respectively), indicating
      that both mechanisms play a role in pathogenesis. Non-dominant yet virulent
      faecal clones or an external source of E. coli seems a possibility in the UV
      group (13.7%, VF score 4.8). In 30% of patients (U group) the infecting urine
      clone was non-dominant and possessed a low virulence score (2.7); suggesting a
      possible role for host factors in establishing infection.

PMID- 24899599
TI  - D-Zone test for detection of inducible clindamycin resistance using SirScan paper
      disks and Rosco Neo-Sensitabs at 25 and 15 mm distances.
AB  - Clindamycin is a possible antibiotic treatment of infections by Gram-positive
      cocci. However, its use can be limited by inducible clindamycin resistance. To
      screen for the presence of this type of resistance, the D-zone test is used. The
      aim of this study was to compare the performance of SirScan paper disks with that
      of Rosco Neo-Sensitabs for the D-zone test at distances according to dispensers
      provided by the manufacturers (25 mm) and when the disks are placed at a distance
      of 15 mm. We studied 364 Gram-stain-positive cocci representing clinical isolates
      that were resistant to erythromycin and susceptible to clindamycin. Out of these
      isolates, 207 (57%) gave a positive D-zone test result at 25 mm distance using
      SirScan paper disks. When the test was repeated with the same disks placed 15 mm
      from the 157 (43%) isolates that had previously given a negative result, 58
      (36.9%) gave a positive D-zone test result. The same isolates were also found to
      test positive when Rosco Neo-Sensitabs were used. Placing the disks at a distance
      of 15 mm instead of 25 mm led to an 84.3% increase in positive D-tests among
      Staphylococcus aureus, 43.8% among group B streptococci (GBS) and 6.4% among
      coagulase-negative staphylococci (CNS). In conclusion, the SirScan paper disks
      are equivalent to Rosco Neo-Sensitabs in screening for inducible resistance to
      clindamycin. The D-test needs to be performed at a shorter distance (15 mm) to
      prevent false-negative reporting.

PMID- 24899597
TI  - Defensive eye-blink startle responses in a human experimental model of anxiety.
AB  - Inhalation of low concentrations of carbon dioxide (CO2) triggers anxious
      behaviours in rodents via chemosensors in the amygdala, and increases anxiety,
      autonomic arousal and hypervigilance in healthy humans. However, it is not known
      whether CO2 inhalation modulates defensive behaviours coordinated by this network
      in humans. We examined the effect of 7.5% CO2 challenge on the defensive eye
      blink startle response. A total of 27 healthy volunteers completed an affective
      startle task during inhalation of 7.5% CO2 and air. The magnitude and latency of
      startle eye-blinks were recorded whilst participants viewed aversive and neutral
      pictures. We found that 7.5% CO2 increased state anxiety and raised concurrent
      measures of skin conductance and heart rate (HR). CO2 challenge did not increase
      startle magnitude, but slowed the onset of startle eye-blinks. The effect of CO2
      challenge on HR covaried with its effects on both subjective anxiety and startle
      latency. Our findings are discussed with reference to startle profiles during
      conditions of interoceptive threat, increased cognitive load and in populations
      characterised by anxiety, compared with acute fear and panic. 

PMID- 24899600
TI  - Pharmacokinetic of four probe drugs in adriamycin-induced nephropathy rat.
AB  - BACKGROUND AND AIM: Probe drugs have been widely used to assess the activities of
      various CYP450 (cytochromes P450) isoenzymes in many fields of drug metabolism
      and pharmacogenetics. The nephrotic syndrome characterized by massive proteinuria
      and hypoproteinemia, whether that would influence the pharmacokinetics of probe
      drugs or not is still unclear. The purpose of the study was to investigate the
      pharmacokinetic of four probe drugs in adriamycin (ADR)-induced nephropathy rat.
      MATERIALS AND METHODS: The rats were randomly divided into Control-group (n = 10)
      and ADR-group (n = 10). Nephrotic syndrome was established by weekly injections
      of ADR for 2 weeks. After dynamic monitoring of 24-h total urinary protein for 4
      weeks, we confirmed that nephrotic syndrome had developed. The rats were
      administered intragastrically with phenacetin, tolbutamide, omeprazole and
      bupropion (15, 5, 15, and 15 mg/kg, respectively). The blood samples were
      determined by LC-MS (Liquid Chromatography-Mass Spectrometry) method. RESULTS:
      The pharmacokinetics parameter of tolbutamide in ADR-group and Control-group were
      AUC(0-t) 15.371 +/- 4.107, 6.901 +/- 5.738 (mg/L*h), MRT(0-t) 8.751 +/- 0.754,
      6.032 +/- 0.63 (h), t1/2 3.88 +/- 0.423, 3.602 +/- 0.693 (h), Tmax 6.2 +/- 3.768,
      1.95 +/- 0.798 (h), CL/F 0.038 +/- 0.005, 0.107 +/- 0.037 (L/h/kg), V/F 0.212 +/-
      0.043, 0.567 +/- 0.258 (L/kg), Cmax 1.853 +/- 0.384, 1.422 +/- 1.312 (mg/L).
      There was statistical difference in AUC, MRT, CL, V and Tmax of tolbutamide
      between two groups (p < 0.05), but no pharmacokinetics difference for phenacetin,
      bupropion and omeprazole. CONCLUSIONS: The pharmacokinetics of tolbutamide was
      changed in ADR-induced nephropathy rat. It is not suitable for tolbutamide to
      evaluate the activity of CYP450 in nephrotic syndrome.

PMID- 24899601
TI  - Preparation and properties of antibacterial polyvinyl chloride.
AB  - BACKGROUND: Plastic products improve people's daily life, but microorganisms
      attaching to plastic product surfaces present health hazards. AIM: Our study
      aimed to design a new kind of antibacterial plastic products to promote a higher
      quality of life. MATERIALS AND METHODS: Antibacterial polyvinyl chloride (PVC)
      composites were prepared using melt-blending. The antibacterial properties,
      mechanical properties, and optical transparencies of the PVC composites
      containing either silver-doped glass or silver-doped zirconium phosphate were
      studied, and the dispersal of these antibacterial agents throughout the PVC was
      also observed using scanning electron microscopy. RESULTS: The results showed
      that the antibacterial agents were well-dispersed throughout the PVC matrix and
      that the antibacterial ratio of PVC-G against Escherichia coli and Staphylococcus
      aureus was over 99.0%, which was better than that of PVC-P. The antibacterial
      agents had little effect on the mechanical properties of the PVC; however, they
      decreased the optical transparency of PVC, and the transmittance of PVC-P was
      decreased by 28.3%. CONCLUSIONS: Our results indicate that such kinds of
      antibacterial PVC composites have great potential in a wide variety of safer
      plastic applications.

PMID- 24899602
TI  - Urethane suppresses renal sympathetic nerve activity in Wistar rats.
AB  - AIM: To investigate the effects of urethane on renal sympathetic nerve activity
      (RSNA) in Wistar rats. MATERIALSAND METHODS: 46 rats were randomly allocated in
      two groups: group A in which rats were injected with urethane; group B in which
      barbital sodium was used as a control. The changes of RSNA, blood pressure (BP)
      and heart rate (HR) of each group were evaluated and analyzed. RESULTS: Compared
      to the control group, the value of RSNA, BP and HR were all significant decreased
      in rats of group A after urethane injection (p < 0.05). CONCLUSIONS: These
      results suggest that urethane could affect RSNA through somatosensory system.

PMID- 24899603
TI  - Effect of exposure to cement dust on Fractional Exhaled Nitric Oxide (FeNO) in
      non-smoking cement mill workers.
AB  - OBJECTIVES: This cross-sectional study aimed to determine the effects of exposure
      to cement dust on Fractional Exhaled Nitric Oxide (FeNO) in non-smoking cement
      mill workers. SUBJECTS AND METHODS: We recruited 121 apparently healthy male
      volunteers, 90 of them were non-smoking cement mill workers and 31 non-smoking un
      exposed subjects served as control. The mean age of cement mill workers was 36.62
      +/- 1.03 years and 36.65 +/- 2.28 years of control subjects. Based on the
      duration of exposure, cement mill workers were divided into four groups, less
      than 5, 5-10, 10-15 and more than 15 years. All subjects were individually
      matched for age, ethnicity and socioeconomic status. Fractional Exhaled Nitric
      Oxide test was performed by using Niox Mino. RESULTS: Significant increased level
      of Fractional Exhaled Nitric Oxide was observed in cement mill workers (31.71 +/-
      2.963 ppb) compared to their non-exposed counterparts (25.39 +/- 2.46 ppb). The
      significance difference was further increased with long-term working exposure in
      cement industry. CONCLUSIONS: Fractional Exhaled Nitric Oxide is significantly
      increased in cement mill workers and associated with duration of exposure to
      cement dust. The findings also show that cement mill workers have higher
      pulmonary inflammation.

PMID- 24899604
TI  - Molecular mechanisms of converting K562/DNR cellular drug-resistance by
      bortezomib.
AB  - OBJECTIVES: The aim of this study was to observe the effects of bortezomib
      (PS341) on the expression of NF-kappaB (nuclear factor-kappa B), IkappaB
      (inhibitor kB) and P-gp (P-glycoprotein) of K562 cells induced by daunorubicin
      (K562/DNR). MATERIALS AND METHODS: MTT method was used to determine the drug
      resistance of K562 cells and the cellular toxicity of bortezomib. Detect the
      expression of NF-kappaB, IkappaB and P-gp of K562/DNR 36 hours after receiving
      the treatment of 100 ug/ml DNR only or added with 0.4 ug/L, 4 ug/L and 40 ug/L
      bortezomib, and 12 hours and 24 hours after receiving the treatment of 100 ug/ml
      DNR only or added with 4 ug/L bortezomib by Western blot. Detect the apoptosis
      rate in each group by flow cytometry respectively and the activity of NF-kappaB
      was detected by ELISA method. RESULTS: Compared with the control group, the
      expressions of NF-kappaB and P-gp in K562/DNR could be induced by DNR. When
      K562/DNR were cultured with bortezomib, the expressions of NF-kappaB and P-gp
      induced by DNR were significantly suppressed and this effcet increased with the
      increase of the concentration or the action time of bortezomib. CONCLUSIONS:
      Proteasome inhibitor bortezomib could convert the cellular drug resistance to
      promote cell apoptosis, and this effect showed the characteristic of
      concentration-dependent and time-dependent pattern.

PMID- 24899605
TI  - Head and neck cancer survivors patients and late effects related to oncologic
      treatment: update of literature.
AB  - Cancer survivorship represents a new challenge in the third Millennium. In Europe
      the number of cancer survivors was estimated to be 17,8 million in 2008 and this
      number is growing. Recent improvements in cancer survival are largely due to
      earlier diagnosis and advancements in treatment. Despite having favorable effects
      on cancer survival, radiation therapy, surgery treatment and combination
      chemotherapy regimens can also cause long-term organ damage and functional
      disabilities. In this paper we review the most important aspects of long-term
      toxicities in otolaryngology cancer survivors patients. 

PMID- 24899606
TI  - Different risk factors of recurrent pulmonary tuberculosis between Tibetan and
      Han populations in Southwest China.
AB  - OBJECTIVE: The geographical environment and living habits are different between
      Tibetan and Han populations. The present study aimed to investigate the risk
      factors of recurrent pulmonary tuberculosis (TB), and analyze the differences
      between the two populations. PATIENTS AND METHODS: A total of 480 TB patients,
      including 80 Tibetan and 80 Han patients with recurrent pulmonary TB, and 320
      patients without recurrent pulmonary TB, were included in present study. All
      patients with pulmonary TB were diagnosed between 2000 and 2001 and followed
      until December 2012. Multivariate logistic regression was used for the
      statistical analysis. RESULTS: Among all patients, the independent risk factors
      associated with recurrent pulmonary TB were no use of directly observed therapy,
      short course (DOTS) (HR 5.867, 95% CI 2.557-13.461), diabetes (HR 3.288, 95% CI
      1.301-8.312), smoking (HR 2.387, 95% CI 1.328-4.291) and malnutrition (HR 1.910,
      95% CI 1.110-3.285). The independent risk factors of recurrent pulmonary TB for
      the Tibetan patients included no use of DOTS and malnutrition, while the
      independent risk factors for the Han patients were diabetes and smoking.
      CONCLUSIONS: The risk factors of pulmonary TB recurrence were different between
      Tibetan and Han patients. To reduce the recurrent rate of pulmonary TB,
      especially for Tibetan populations, pursuing high-quality DOTS is essential.

PMID- 24899607
TI  - The visual diagnosis of tuberculous pleuritis under medical thoracoscopy: a
      retrospective series of 91 cases.
AB  - BACKGROUND: Despite progress of medical, the fast and accurate diagnosis of
      tuberculous pleuritis (TP) continues to be a challenge, mainly because of the
      lack of specific clinical features and the difficulty in isolating the
      Mycobacterium tuberculosis. OBJECTIVES: To investigate the role of medical
      thoracoscopy in definite diagnosis of tuberculous pleuritis, especially the
      feature of visual diagnosis in tuberculous pleuritis via medical thoracoscopy. We
      performed a retrospective review of the utility of medical thoracoscopy in
      tuberculous pleuritis. PATIENTS AND METHODS: A retrospective chart review was
      performed of 91 patients who had medical thoracoscopy for suspected TP at the
      Second Xiangya Hospital from October 1, 2006 to July 30, 2012. RESULTS: In ninety
      one cases, 76 patients were diagnosed with TP by pathologic diagnosis. The visual
      findings via thoracoscopy of 76 TP patients included the following: (1) necrosis
      (76.32%, n=58), (2) diffuse miliary nodules (64.67%, n=49), (3) single or
      multiple pleural nodules (14.47%, n=11), (4) hyperemic, edematous and thickened
      pleura (56.58%, n=43), and (5) pleural adhesions or fibrotic septa (78.95%,
      n=60), and all of these samples had hydrothorax or loculated effusion. The
      diagnostic efficiency of visual diagnosis via medical thoracoscopy about
      tuberculous pleuritis was 93.41%. In the non-invasive test, ADA > 40 u/l with LDH
      > 200 u/l for TP showed relatively high sensitivity and specificity (73.68%,
      80.00%, respectively). CONCLUSIONS: TP presents a variety of scopic phenotypes
      under medical thoracoscopy. The experienced pulmonologists visually diagnose TP
      efficiently and directly via medical thoracoscopy. Medical thoracoscopy with
      combined biopsy is an accurate and safe method for diagnosing TP.

PMID- 24899608
TI  - Relationship between adiposity, adipokines, inflammatory markers and lipid
      profile in hemodialysis patients.
AB  - OBJECTIVES: Our aim is to study the correlations of leptin and adiponectin with
      inflammation markers, body composition and lipid profile in end stage renal
      disease (ESRD) patients. PATIENTS AND METHODS: Phase angle values and fat mass as
      calculated using BIA, Malnutrition-Inflammation Score (MIS), leptin, adiponectin,
      IL-6, IL-8 triglycerides, cholesterol and other common serum markers'
      concentrations were analyzed using simple and multiple linear regression models
      in 47 hemodialysis patients. RESULTS: In contrast to leptin, adiponectin is
      inversely correlated to BMI and fat mass in hemodialysis patients. Triglycerides
      were the only parameter that retained its statistical correlation significance
      with adiponectin in the multiple regression model. CONCLUSIONS: Fat mass is of
      important consideration when calculating adipokines levels and their possible
      correlations with other variables. The inverse correlation of adiponectin with
      triglycerides levels should be further delineated due to the important role of
      vascular diseases in total mortality and morbidity of ESRD patients.

PMID- 24899609
TI  - Regional differences in diabetic patients' pharmacotherapy in Bulgaria.
AB  - BACKGROUND: The regional analyses play an important role in understanding a state
      of diabetes mellitus management and to support informed policy options. They need
      to be explored in more details in order to ensure an equal patients' access to
      health care services of the same value and quality. AIM: The aim of this study is
      to analyze regional differences in a cost of diabetes therapy for insulin users
      in Bulgaria. MATERIALS AND METHODS: It is a combined prospective and
      retrospective observational study with duration of 6 months. Diabetic patients on
      insulin therapy were recruited by 35 endocrinologists. Information about the
      health care resources used was collected within 3-prospective and 3 retrospective
      months in 2010 and 2011. The regional cost of illness analysis was performed by
      calculating the average cost attributable to each individual patient despite the
      fact that some might not use a particular health care resource. Subgroup analysis
      was performed for hospitalized patients. RESULTS: A detailed analysis revealed
      cost differences in the regions, especially with more vulnerable population like
      Burgas and Pleven regions. Another reason for the cost differences is the type of
      insulin or type of therapy. Our study confirms the fact that the hospitalizations
      are the major cost driver. Rising diabetes prevalence and associated costs,
      including hospitalizations and management of diabetes complications, are a
      growing concern. The last possible reason for regional differences is the
      patients' characteristics and therapy differences. We add evidence demonstrating
      that the patients on insulin and OAD consume more resources including
      hospitalizations and suffer from more complications of diabetes. CONCLUSIONS:
      Reasons for regional differences might have different origin as there are various
      population characteristics, type of therapy, socio economic status and others.

PMID- 24899610
TI  - Gastrointestinal tract duplications in children.
AB  - AIM: Gastrointestinal tract duplications (GTD) are rare congenital abnormalities
      that can occur anywhere along the gastrointestinal tract. These anomalies may
      present as a single, multiple, or a vague pathologies. Diagnosing and treating
      these diseases may be difficult in some patients. We aimed to present 32 patients
      who were followed and treated in our clinic. PATIENTS AND METHODS: This study
      included the patients between 2000 and 2013. Evaluations included clinical
      presentations, diagnostic strategies and algorithms, surgical procedures and
      associated anomalies, and presence of ectopic tissue, complications, and
      prognosis. RESULTS: Common clinical presentations included vomiting (n=8; 25%),
      palpable abdominal mass (n=4; 13%). Twenty-eight patients (2 of them antenatally)
      were diagnosed preoperatively while four of them were diagnosed at surgery. Ileal
      duplications constituted the most common type (34%) while the least common ones
      were located in appendix, thoracoabdomen and rectum. One of our patients was
      present with a gastric duplication which was closely interconnected to a tubular
      duplication of esophagus, which had never been encountered in the literature
      before. CONCLUSIONS: It is crucial to note that duplications are likely to occur
      in various types and numbers and also may accompany other anomalies. Computed
      Tomography (CT) remains the method of choice since Magnetic Resonance (MR) is
      likely to cause the use of sedation and analgesia at very young ages and it may
      also be relatively costly despite being more sensitive in soft tissues. Mucosal
      stripping is an ideal method for the patients requiring restricted surgery. The
      antenatal asymptomatic cases can be operated after their 6th months of age.

PMID- 24899611
TI  - Diagnostic value of analysis of H-FABP, NT-proBNP, and cTnI in heart function in
      children with congenital heart disease and pneumonia.
AB  - AIM: To analyze the expression of heart-fatty acid-binding protein (H-FABP), N
      terminal pro-brain natriuretic peptide (NT-proBNP), and cTnI in children with
      congenital heart disease (CHD) and pneumonia, and evaluate its diagnostic value
      in heart failure (HF). PATIENTS AND METHODS: The levels of serum H-FABP, NT
      proBNP, and cardiac troponin 1 (cTnI) were measured by immunoassays in 22
      children with CHD, pneumonia, and HF (group I), 25 children with CHD and
      pneumonia (group II), and 25 healthy children without CHD or pneumonia (control
      group). RESULTS: The concentration and positive rate of serum H-FABP, NT-proBNP,
      and cTnI were significantly higher in group I than those in group II. Compared to
      control group, these indexes were increased in both group I and group II. There
      were statistical significant differences in the positive rate of NT-proBNP and
      cTnI but not H-FABP between groups of patients with different classes of heart
      function. CONCLUSIONS: The levels of H-FABP, NT-proBNP, and cTnI were correlated
      with heart function, and can be used for the diagnosis of early-stage HF in
      children with CHD.

PMID- 24899612
TI  - Propofol protects against hydrogen peroxide-induced apoptosis in cardiac H9c2
      cells is associated with the NF-kappaB activation and PUMA expression.
AB  - BACKGROUND AND AIMS: Treatment with propofol has been found to attenuate
      oxidative stress injury in rat cardiac cells through the inhibition of programmed
      cell death. However, the underlying mechanism of this beneficial effect is not
      clear. Previous studies showed NF-kappaB (NF-kappaB) could be activated after
      oxidative stress in cardiac cells, and p53 up-regulated modulator of apoptosis
      (PUMA) is a direct target of NF-kappaB and mediates oxidative stress -induced
      apoptosis. Here, we report that propofol protects cardiac H9c2 cells from
      hydrogen peroxide (H2O2)-induced apoptosis by preventing the activation of NF
      kappaB and PUMA upregulation. MATERIALS AND METHODS: We first determined NF
      kappaB activity, PUMA expression, proliferation and apoptosis after hydrogen
      peroxide treatment of the H9c2 cell line using electrophoretic mobility shift
      assay (EMSA), western blot assay, MTT and annexin V/PI assay. We, then, examined
      the effect of inhibition of NF-kappaB activity on the PUMA expression and
      hydrogen peroxide (H2O2)-induced apoptosis.We next examined the effect of
      inhibition of PUMA on hydrogen peroxide (H2O2)-induced apoptosis. In the end, we
      examined the effect of propofol pretreatment on NF-kappaB activity, PUMA
      expression and hydrogen peroxide (H2O2)-induced apoptosis. RESULTS: We show that
      H2O2 treatment led to increases in NF-kappaB activity, PUMA protein levels in
      cardiac H9c2 cells. The induction of PUMA was mediated by the p65 component of NF
      kappaB. The apoptotic effect of PUMA induction by H2O2 was in an NF-kappaB
      dependent manner. We, further, demonstrate that pretreatment with propofol
      significantly decreased H2O2-induced apoptosis. Furthermore, propofol inhibits
      H2O2 induced NF-kappaB activity and subsequent PUMA expression. CONCLUSIONS: our
      results reveal a new mechanism by which propofol inhibits H2O2-induced injury in
      cardiac H9c2 cells via decreasing NF-kappaB activation and PUMA expression. This
      inhibition improves cell survival, which provides a novel explanation for the
      pleiotropic effects of propofol that benefit the cardiac cells.

PMID- 24899613
TI  - Elevated plasma levels and monocyte-associated expression of CD137 ligand in
      patients with acute atherothrombotic stroke.
AB  - BACKGROUND: CD137 ligand (CD137L) is expressed by various immune cells and exists
      in membrane-bound and soluble forms. Recently, CD137L was found to be localized
      to macrophages in human atherosclerotic lesions and CD137L levels were much
      higher in atherosclerotic lesions than in normal arteries. However, the role of
      CD137L with different forms in atherothrombotic stroke remains unclear. PATIENTS
      AND METHODS: The soluble CD137L (sCD137L) protein and CD137L expression on
      monocytes were analyzed by an enzyme-linked immunosorbent assay and flow
      cytometry in peripheral blood of patients with acute ischemic atherosclerotic
      stroke, atherosclerosis controls and normal controls. RESULTS: During the initial
      24h after onset, the stroke patients had elevated plasma sCD137L levels (133.2
      pg/ml) and CD137L expression on monocytes [7.9 +/- 4.1%, 7.0 +/- 4.0 mean
      fluorescence intensity (MFI)] as compared with normal controls (75 pg/ml, p <
      0.05; 4.6 +/- 2.4%, 4.1 +/- 2.7 MFI, p < 0.05). CONCLUSIONS: The dysregulation of
      CD137L expression may reflect a persistent chronic inflammatory response that may
      have been induced during early stages of the disease. Our results strongly
      suggest that the abnormal expression of CD137L on monocytes may lead to
      dyregulated CD137L/CD137 signaling and consequently form part of a positive
      feedback, inflammation-promoting circuit in stroke, while the elevated sCD137L
      protein levels may function as a self-regulatory mechanism of CD137/CD137L
      interaction and costimulation.

PMID- 24899614
TI  - Deafness in Italy: an epidemiological and socio-demographic study.
AB  - OBJECTIVES: Hearing loss is very common in our society, but epidemiological data
      on deafness in Italy is lacking. A.I.R.S. onlus (Italian Association for Research
      on Deafness) yearly launches the National Day for the Fight Against Deafness
      (NDFAD). During this events, that are held every year, it is possible to perform
      a free hearing test in all the facilities that have joined the initiative
      throughout Italy (240 hospitals joined in 2011). AIM: to report data collected
      throughout the "A.I.R.S. National Day for the Fight against Deafness" of the last
      years, focusing in particular but not only on audiometric outcomes. METHODS:
      demographic and social data, as well as audiometric outcomes, was collected on
      forms that have been subsequently stored in a on-line database and analyzed with
      MySQL and Microsoft Excel. CONCLUSIONS: This data are important in order to
      describe the "hearing health" of the Italian population, and is a first step
      towards creating a database with epidemiological and preventive aims, a strongly
      felt need both at national and at regional level.

PMID- 24899615
TI  - Detection of common deafness mutation by maternal plasma cell-free DNA.
AB  - OBJECTIVES: The aim is to investigate the use of the ligase detection reaction
      (LDR) microarray to examine the difference of the single nucleotide between the
      pregnant woman and the fetus by cell-free DNA in the maternal plasma in
      congenital deafness. MATERIALS AND METHODS: The proband and the couples' venous
      blood samples and the amniotic fluid/ chorionic villi collected from seven
      deafness families for prenatal diagnosis were analyzed. The cell-free DNA from
      maternal plasma was examined to determine if they carried the mutations of GJB2
      235delC. RESULTS: Three samples were found to carry the mutation of GJB2 235delC.
      It is in agreement with the sequencing results. The affected fetuses were
      suggested to take invasive procedure for confirmation. CONCLUSIONS: The chip may
      be a potential method to screen for congenital deafness based on maternal plasma
      DNA.

PMID- 24899617
TI  - Plasma levels of growth arrest specific protein 6 are increased in idiopathic
      recurrent pregnancy loss.
AB  - AIM: The aim of this study was to determine plasma Growth Arrest Specific Protein
      6 (GAS6) protein levels in patients with unexplained recurrent pregnancy loss
      (RPL) and compare them to those of pregnant and to healthy non-pregnant women
      with a history of at least one live delivery. PATIENTS AND METHODS: A total of
      205 women were included in the study. Of these, 68 were diagnosed with
      unexplained RPL and were not pregnant at the time of the study. The second group
      consisted of 67 pregnant women in the third trimester of pregnancy. The third
      group constituted the control group of 70 healthy non-pregnant women who had at
      least one live birth. Plasma levels of GAS6 protein were measured by ELISA.
      RESULTS: Mean plasma GAS6 levels were found to be different between RPL group and
      healthy non-pregnant women (12.17 +/- 4.39 ug/L  and 9.18 +/- 4.65, respectively,
      p = 0.0013). Although it was not statistically significant, plasma levels of GAS6
      in the third trimester pregnant group (10.65 +/- 3.74 ug/L) were found to be
      slightly higher than non-pregnant controls, and slightly lower than RPL group. In
      comparison of those with 2 or more than 2 pregnancy losses in the RPL group,
      there was no difference between these two subgroups in terms of GAS6 levels
      (12.39 +/- 4.27 ug/L and 11.83 +/- 4.63 ug/L, respectively, p = 0.62).
      CONCLUSIONS: Our findings revealed that plasma GAS6 levels were increased in
      patients with RPL. The prothombotic and proinflammatory nature of the GAS 6
      protein makes it a likely culprit involved in the pathologic process in patients
      with RPL. Further studies are warranted to determine the possible role of GAS6
      protein in the pathophysiology of idiopathic RPL.

PMID- 24899616
TI  - Evaluation of preoperative and postoperative S-100B levels in children with
      chronic adenotonsillar hypertrophy: preliminary results.
AB  - OBJECTIVES: Upper air obstruction leads hypoxia, it is also known that S-100B
      levels increase by glial activations indicate cerebral hypoxic injury. This study
      aimed to evaluate the preoperative and postoperative S-100B levels in children
      with chronic adenotonsillar hypertrophy. PATIENTS AND METHODS: The study
      comprised 40 patients with indications for tonsillectomy and/or adenoidectomy
      following a diagnosis of chronic adenotonsillar hypertrophy and 40 age-gender
      matched control patients. Blood samples were taken from the patients
      preoperatively and at four weeks postoperatively. Preoperative and postoperative
      serum S-100B levels were analyzed. RESULTS: The serum S-100B levels in the
      preoperative period were found to be significantly higher compared to those of
      the control group (p < 0.05). The S-100B levels were significantly decreased in
      the postoperative period (p < 0.05). CONCLUSIONS: The development of chronic
      adenotonsillar hypertrophy would play a role in increased S-100B levels. This
      indicates that neuronal damage would exists in patients with chronic
      adenotonsillar hypertrophy.

PMID- 24899619
TI  - iPhone-responsive functional gait disorder.

PMID- 24899618
TI  - Protective effect of ischaemic preconditioning in total knee arthroplasty.
AB  - OBJECTIVE: To investigate the genomic response induced by ischaemic
      preconditioning (IPC) in muscle biopsies taken from the operative leg of total
      knee arthroplasty patients. MATERIALS AND METHODS: The gene expression profile
      GSE21164 was extracted from Gene Expression Omnibus (GEO) database. Patients
      undergoing primary knee arthroplasty were randomized to control and treatment
      (IPC) groups. Muscle biopsies were taken from the quadriceps muscle of the
      operative knee at the immediate onset of surgery (T0) and at 1 hour into surgery
      (T1). Limma package of R language was used to identify the differentially
      expressed genes (DEGs) between control and treatment group. To find out specific
      genes, DEGs at T0 were compared with DEGs at T1. Scansite was used to find out
      the binding domain for specific DEGs. Functional enrichment analysis was done by
      DAVID. RESULTS: Of the genes queried on the Affymetrix Human Genome U133 Plus 2.0
      microarray, we identified 263 (T0) and 266 (T1) DEGs compared to the control
      group. Down-regulation of DEGs related with regulation neuron apoptosis was
      observed at T1. The most significant function of DEGs at T0 was related with
      neurological system process. The most specific DEG was FAM125B at T0 and T1 time
      points. Its common binding domain was SH3. CONCLUSIONS: The protective effect of
      IPC was associated with altered expression of genes involved in neurological
      system process and regulation of neuron apoptosis. The dynamic expression of
      FAM125B can be a supervised marker during the surgery. IPC may be of potential
      benefit in this and other musculoskeletal conditions.

PMID- 24899620
TI  - Optical conductivity of iron-based superconductors.
AB  - The new family of unconventional iron-based superconductors discovered in 2006
      immediately relieved their copper-based high-temperature predecessors as the most
      actively studied superconducting compounds in the world. The experimental and
      theoretical effort made in order to unravel the mechanism of superconductivity in
      these materials has been overwhelming. Although our understanding of their
      microscopic properties has been improving steadily, the pairing mechanism giving
      rise to superconducting transition temperatures up to 55 K remains elusive. And
      yet the hope is strong that these materials, which possess a drastically
      different electronic structure but similarly high transition temperatures
      compared to the copper-based compounds, will shed essential new light onto the
      several-decade-old problem of unconventional superconductivity. In this work we
      review the current understanding of the itinerant-charge-carrier dynamics in the
      iron-based superconductors and parent compounds largely based on the optical
      conductivity data the community has gleaned over the past seven years using such
      experimental techniques as reflectivity, ellipsometry, and terahertz transmission
      measurements and analyze the implications of these studies for the microscopic
      properties of the iron-based materials as well as the mechanism of
      superconductivity therein.

PMID- 24899622
TI  - Low-frequency anomalies in dynamic localization.
AB  - Quantum mechanical spreading of a particle hopping on tight binding lattices can
      be suppressed by the application of an external ac force, leading to periodic
      wave packet reconstruction. Such a phenomenon, referred to as dynamic
      localization (DL), occurs for certain 'magic' values of the ratio Gamma =
      F0/omega between the amplitude F0 and frequency omega of the ac force. It is
      generally believed that in the low-frequency limit (omega -> 0) DL can be
      achieved for an infinitesimally small value of the force F0, i.e. at finite
      values of Gamma. Such normal behavior is found in homogeneous lattices as well as
      in inhomogeneous lattices of the Glauber-Fock (GF) type. Here we introduce a
      tight-binding lattice model with inhomogeneous hopping rates, referred to as a
      pseudo-GF lattice, which shows DL but fails to reproduce the normal low-frequency
      behavior of homogeneous and GF lattices. In pseudo-GF lattices, DL can be exactly
      realized; however, at the DL condition the force amplitude F0 remains finite as
      omega -> 0. Such an anomalous behavior is explained in terms of a PT symmetry
      breaking transition of an associated two-level non-Hermitian Hamiltonian that
      effectively describes the dynamics of the Hermitian lattice model.

PMID- 24899621
TI  - Methods comparison.
AB  - The current report discusses the process in which a methods comparison study in
      the National Animal Health Laboratory Network is performed. Specific details are
      provided for designing and analyzing studies intended to evaluate analytical
      sensitivity, efficiency, analytical specificity, cross-contamination,
      repeatability, operator variability, and to compare the performance of methods
      using diagnostic samples. As an example, a case study is presented comparing the
      performance of a candidate reverse transcription polymerase chain reaction (RT
      PCR) chemistry to the current RT-PCR chemistry in use when the assay was
      originally validated. The present study revealed that, for all of the validation
      factors evaluated, the candidate method performed at least as well and generally
      better than the current method. The candidate method was, therefore, deemed fit
      for the original intended purpose of the current method and rendered acceptable
      for use. A discussion of the case study is intended to further motivate
      consideration of the study designs chosen.

PMID- 24899623
TI  - A motif in LILRB2 critical for Angptl2 binding and activation.
AB  - A better understanding of the interaction between extrinsic factors and surface
      receptors on stem cells will greatly benefit stem cell research and applications.
      Recently, we showed that several angiopoietin-like proteins (Angptls) bind and
      activate the immune inhibitory receptor human leukocyte immunoglobulin (Ig)-like
      receptor B2 (LILRB2) to support ex vivo expansion of hematopoietic stem cells
      (HSCs) and leukemia development. However, the molecular basis for the interaction
      between Angptls and LILRB2 was unclear. Here, we demonstrate that Angptl2
      expressed in mammalian cells forms high-molecular-weight species and that ligand
      multimerization is required for activation of LILRB2 for downstream signaling. A
      novel motif in the first and fourth Ig domains of LILRB2 was identified that is
      necessary for the receptor to be bound and activated by Angptl2. The binding of
      Angptl2 to LILRB2 is more potent than and not completely overlapped with the
      binding of another ligand, HLA-G. Immobilized anti-LILRB2 antibodies induce a
      more potent activation of LILRB2 than Angptl2, and we developed a serum-free
      culture containing defined cytokines and immobilized anti-LILRB2 that supports a
      net expansion of repopulating human cord blood HSCs. Our elucidation of the mode
      of Angptl binding to LILRB2 enabled the development of a new approach for ex vivo
      expansion of human HSCs.

PMID- 24899626
TI  - Thermoelectric cooler concepts and the limit for maximum cooling.
AB  - The conventional analysis of a Peltier cooler approximates the material
      properties as independent of temperature using a constant properties model (CPM).
      Alternative concepts have been published by Bian and Shakouri (2006 Appl. Phys.
      Lett. 89 212101), Bian (et al 2007 Phys. Rev. B 75 245208) and Snyder et al (2012
      Phys. Rev. B 86 045202). While Snyder's Thomson cooler concept results from a
      consideration of compatibility, the method of Bian et al focuses on the
      redistribution of heat. Thus, both approaches are based on different principles.
      In this paper we compare the new concepts to CPM and we reconsider the limit for
      maximum cooling. The results provide a new perspective on maximum cooling.

PMID- 24899624
TI  - Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case
      control study in the prospective EPIC cohort.
AB  - It has been suggested that mitochondrial dysfunction and DNA damage are involved
      in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a
      compensatory mechanism of mitochondrial dysfunction previously has been
      associated with B-cell lymphomas, in particular chronic lymphocytic leukemia
      (CLL). However, current evidence is limited and based on a relatively small
      number of cases. Using a nested case-control study, we extended these findings
      with a focus on subtype-specific analyses. Relative mtDNA copy number was
      measured in the buffy coat of prospectively collected blood of 469 lymphoma cases
      and 469 matched controls. The association between mtDNA copy number and the risk
      of developing lymphoma and histologic subtypes was examined using logistic
      regression models. We found no overall association between mtDNA and risk of
      lymphoma. Subtype analyses revealed significant increased risks of CLL (n = 102)
      with increasing mtDNA copy number (odds ratio = 1.34, 1.44, and 1.80 for
      quartiles 2-4, respectively; P trend = .001). mtDNA copy number was not
      associated with follow-up time, suggesting that this observation is not strongly
      influenced by indolent disease status. This study substantially strengthens the
      evidence that mtDNA copy number is related to risk of CLL and supports the
      importance of mitochondrial dysfunction as a possible mechanistic pathway in CLL
      ontogenesis. 

PMID- 24899627
TI  - Evolution of Escherichia coli for maximum HOCl resistance through constitutive
      expression of the OxyR regulon.
AB  - Exposure of cells to stress impairs cellular functions and may cause killing or
      adaptation. Adaptation can be facilitated by stress-induced mutagenesis or
      epigenetic changes, i.e. phenotypic variation without mutations. Upon exposure to
      HOCl, which is produced by the innate immune system upon bacterial infection,
      bacteria trigger stress responses that enable increased survival against the
      stress. Here, we addressed the question whether bacteria can adapt to high HOCl
      doses and if so, how the acquired resistance is facilitated. We evolved
      Escherichia coli cells for maximum HOCl resistance by successively increasing the
      HOCl concentration in the cultivation medium. HOCl-resistant cells showed broad
      stress resistance but did not carry any chromosomal mutations as revealed by
      whole-genome sequencing. According to proteome analysis and analysis of
      transcript levels of stress-related genes, HOCl resistance was accompanied by
      altered levels of outer-membrane proteins A, C, F and W, and, most prominently, a
      constitutively expressed OxyR regulon. Induction of the OxyR regulon is
      facilitated by a partially oxidized OxyR leading to increased levels of
      antioxidant proteins such as Dps, AhpC/AhpF and KatG. These changes were
      maintained in evolved strains even when they were cultivated without stress for a
      prolonged time, indicating epigenetic changes contributed to stress resistance.
      This indicated that maximum HOCl resistance was conferred by the accumulated
      action of the OxyR stress response and other factors such as altered levels of
      outer-membrane proteins. 

PMID- 24899625
TI  - Upregulation of hepatic VLDLR via PPARalpha is required for the triglyceride
      lowering effect of fenofibrate.
AB  - The liver and the VLDL receptor (VLDLR) play major roles in TG and VLDL
      metabolism. However, the exact role of liver VLDLR is not well known because of
      the absence of or difficulty in detecting VLDLR in the liver. In this study, we
      demonstrate that fenofibrate, a PPARalpha agonist and widely used TG-lowering
      drug, markedly upregulated hepatic VLDLR, which is essential for lowering TG.
      This study also shows that the distinct regulatory roles of PPARalpha agonists on
      VLDLR in the liver and peripheral tissues including adipose tissues, heart, and
      skeletal muscles are due to the pattern of expression of PPARalpha. The in vivo
      portion of our study demonstrated that oral fenofibrate robustly increased liver
      VLDLR expression levels in hyperlipidemic and diabetic mice and significantly
      reduced the increase in serum TG observed in wt mice after feeding with high-fat
      diet (HFD) but not in Vldlr(-/-) mice or Pparalpha(-/-) mice. However,
      overexpression of mouse VLDLR in livers of Vldlr(-/-) mice significantly
      prevented the increase in serum TG induced by HFD. The in vitro portion of our
      study showed that fenofibrate upregulated VLDLR transcriptional activity through
      PPAR response element binding to the VLDLR promoter. The conclusions of our study
      provide a novel mechanism for the TG-lowering effects of fenofibrate in the
      treatment of dyslipidemia. 

PMID- 24899629
TI  - Strain tuning of magnetism in Mn doped MoS2 monolayer.
AB  - We study the strain tuning of magnetism in Mn doped MoS2 monolayer system. With
      the increase of the tensile strain, the magnetic ground state changes from a
      state with total magnetic moment Mtot =1.0 B to another state with Mtot =3.0 B
      for single doping in a 4 * 4 supercell. Physical mechanism is elucidated from the
      effects of the local bonding and geometry symmetries on orbital hybridization. In
      addition, we find the ferromagnetic coupling is favored for small distances
      between Mn atoms corresponding to the uniform doping concentration of 25%. More
      importantly, the ferromagnetic state is highly stable and robust to tensile
      strains. Therefore, diluted magnetic semiconductors can be obtained and the
      strain engineering should be a very promising approach to tune the magnetic
      moments.

PMID- 24899630
TI  - Hospital and GMC investigate apparent irregularities in heart surgeon's data.

PMID- 24899628
TI  - Selection of pancreatic cancer cell-binding landscape phages and their use in
      development of anticancer nanomedicines.
AB  - It is hypothesized that the use of targeted drug delivery systems can
      significantly improve the therapeutic index of small molecule chemotherapies by
      enhancing accumulation of the drugs at the site of disease. Phage display offers
      a high-throughput approach for selection of the targeting ligands. We have
      successfully isolated phage fusion proteins selective and specific for PANC-1
      pancreatic cancer cells. Doxorubicin liposomes (Lipodox) modified with tumor
      specific phage fusion proteins enhanced doxorubicin uptake specifically in PANC-1
      cells as compared with unmodified Lipodox and also compared with normal breast
      epithelial cells. Phage protein-targeted Lipodox substantially increased the
      concentration of doxorubicin in the nuclei of PANC-1 cells in spite of P
      glycoprotein-mediated drug efflux. The in vitro cytotoxic activity obtained with
      pancreatic cell-targeted Lipodox was greater than that of unmodified Lipodox. We
      present a novel and straightforward method for preparing pancreatic tumor
      targeted nanomedicines by anchoring pancreatic cancer-specific phage proteins
      within the liposome bilayer. 

PMID- 24899631
TI  - Orange stains in a healthy neonate's diaper.

PMID- 24899632
TI  - Hypertension during intravenous immune globulin infusion for Kawasaki's disease:
      an underreported phenomenon?

PMID- 24899635
TI  - From harm to hope and purposeful action: what could we do after Francis?
AB  - Responses to the reports on the inquiry into Mid Staffordshire have resulted in
      calls from politicians, NHS leaders and the public to improve care across the NHS
      in England. However, the substance of what needs to be done remains unclear. In
      this paper, we offer seven key 'ingredients' required to sustain improvement of
      care, supported by evidence drawn from published literature. We believe that
      empowering and upskilling the front-line workforce in understanding and
      implementing improvement techniques, supported by changes at system and policy
      level and reinforced by what leaders say and do, will result in sustainable
      benefit for patients and families, as well as greater satisfaction for staff. 

PMID- 24899633
TI  - Rehospitalization during the first year of life by insurance status.
AB  - OBJECTIVE: To assess the association of insurance status on infant
      rehospitalization in a population-based setting. METHODS: In this longitudinal
      retrospective study, hospitalizations were tracked for 1 year after birth
      discharge for 203 031 infants born in hospitals during 2008 using data from the
      New York State Inpatient Database. Relative risk was estimated using
      multivariable negative binomial regression models. RESULTS: Rehospitalization
      occurred in 9010 infants (4.4%). Medicaid coverage and being uninsured were
      strong predictors of rehospitalizations after adjustment for birth weight and
      other factors. Medicaid also bears a disproportionate share of the economic
      burden. Normal birth weight infants have the lowest risk, but comprise the
      majority of costs. Jaundice and acute bronchiolitis were the leading causes of
      rehospitalization within 30 days and 1 year, respectively. DISCUSSION: Future
      research can explore the preventability of rehospitalizations, and evaluate novel
      strategies for discharge and postnatal care coordination especially for uninsured
      and Medicaid-enrolled infants.

PMID- 24899634
TI  - Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in
      vivo using phase shift nanoemulsions.
AB  - Advanced tumors are often inoperable due to their size and proximity to critical
      vascular structures. High intensity focused ultrasound (HIFU) has been developed
      to non-invasively thermally ablate inoperable solid tumors. However, the clinical
      feasibility of HIFU ablation therapy has been limited by the long treatment times
      (on the order of hours) and high acoustic intensities required. Studies have
      shown that inertial cavitation can enhance HIFU-mediated heating by generating
      broadband acoustic emissions that increase tissue absorption and accelerate HIFU
      induced heating. Unfortunately, initiating inertial cavitation in tumors requires
      high intensities and can be unpredictable. To address this need, phase-shift
      nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid
      perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing
      passive accumulation in tumors through leaky tumor vasculature. PSNE can be
      vaporized into microbubbles in tumors in order to nucleate cavitation activity
      and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were
      performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of
      vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were
      delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation
      emissions were recorded with a 650 kHz ring hydrophone while temperature was
      monitored using MR thermometry. Cavitation emissions were significantly higher (P
      < 0.05) after PSNE injection and this was well correlated with enhanced HIFU
      mediated heating in tumors. The peak temperature rise induced by sonication was
      significantly higher (P < 0.05) after PSNE injection. For example, the mean per
      cent change in temperature achieved at 5.2 W of acoustic power was 46 +/- 22%
      with PSNE injection. The results indicate that PSNE nucleates cavitation which
      correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE
      could potentially be used to reduce the time and/or acoustic intensity required
      for HIFU-mediated heating, thereby increasing the feasibility and clinical
      efficacy of HIFU thermal ablation therapy. 

PMID- 24899637
TI  - Immunoglobulin-like transcripts 6 (ILT6) polymorphism influences the anti-Ro60/52
      autoantibody status in South Indian SLE patients.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystem autoimmune
      disorder with complex etiology. Loss of immune tolerance against self-antigens
      results in activation of the immune system to produce autoantibodies, which in
      turn contribute to the clinical manifestations of the disease. Immune cells
      harbor a plethora of regulatory receptors. Immunoglobulin-like transcripts (ILTs)
      exhibit both immune activation and inhibitory properties. Genetic defects in
      genes encoding these receptors may predispose to development of autoimmune
      diseases secondary to loss of their function. The aim of our study was to analyze
      the presence or absence of the 6.7 kb segment in the ILT6 gene and its
      association with susceptibility to SLE and its different manifestations. METHOD:
      A total of 188 SLE patients and 192 age-, sex similar-, ethnicity-matched
      controls were recruited. They were genotyped to test the presence or absence of
      the 6.7 kb segment of the ILT6 gene by polymerase chain reaction. RESULTS: The
      mutant allele lacking the 6.7 kb gene segment had an equal frequency in patients
      as well as controls (20% and 18%, respectively). The mutant allele was not
      associated with SLE or its clinical manifestations. However, the mutant allele
      was associated with the presence of anti-Ro60 (p = 0.0005, OR 3.5, 95% CI 1.8
      7.1) and anti-Ro52 (p = 0.0027, OR 2.99, 95% CI 1.5-6.06) autoantibodies.
      CONCLUSION: ILT6 deletion polymorphism does not appear to be a lupus
      susceptibility gene in South Indian Tamils, but may behave as a genetic modifier
      of autoantibody phenotype by influencing the production of anti-Ro60 and anti
      Ro52 autoantibodies and thus indirectly contribute to autoimmune responses in
      SLE.

PMID- 24899638
TI  - Mycophenolate mofetil in the treatment of lupus vasculopathy.

PMID- 24899636
TI  - Mitochondrial DNA damage is associated with damage accrual and disease duration
      in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the extent of mitochondrial DNA (mtDNA) damage in
      systemic lupus erythematosus (SLE) patients compared to healthy subjects and to
      determine the factors associated with mtDNA damage among SLE patients. METHODS: A
      cross-sectional study was performed in 86 SLE patients (per American College of
      Rheumatology classification criteria) and 86 healthy individuals matched for age
      and gender. Peripheral blood mononuclear cells (PBMCs) were collected from
      subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase
      chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA
      abundance. Socioeconomic-demographic features, clinical manifestations,
      pharmacologic treatment, disease activity, and damage accrual were determined.
      Statistical analyses were performed using t test, pairwise correlation, and
      Pearson's chi-square test (or Fisher's exact test) as appropriate. RESULTS: Among
      SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the
      mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased
      levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased
      mtDNA abundance as compared to healthy individuals. There was a negative
      correlation between disease damage and mtDNA abundance and a positive correlation
      between mtDNA lesions and disease duration. No association was found between
      disease activity and mtDNA damage. CONCLUSION: PBMCs from SLE patients exhibited
      more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage
      were observed among SLE patients with major organ involvement and damage accrual.
      These results suggest that mtDNA damage have a potential role in the pathogenesis
      of SLE.

PMID- 24899639
TI  - Analysis shows "postcode lottery" in access to GPs in England.

PMID- 24899640
TI  - HSP70-binding protein HSPBP1 regulates chaperone expression at a
      posttranslational level and is essential for spermatogenesis.
AB  - Molecular chaperones play key roles during growth, development, and stress
      survival. The ability to induce chaperone expression enables cells to cope with
      the accumulation of nonnative proteins under stress and complete developmental
      processes with an increased requirement for chaperone assistance. Here we
      generate and analyze transgenic mice that lack the cochaperone HSPBP1, a
      nucleotide-exchange factor of HSP70 proteins and inhibitor of chaperone-assisted
      protein degradation. Male HSPBP1(-/-) mice are sterile because of impaired
      meiosis and massive apoptosis of spermatocytes. HSPBP1 deficiency in testes
      strongly reduces the expression of the inducible, antiapoptotic HSP70 family
      members HSPA1L and HSPA2, the latter of which is essential for synaptonemal
      complex disassembly during meiosis. We demonstrate that HSPBP1 affects chaperone
      expression at a posttranslational level by inhibiting the ubiquitylation and
      proteasomal degradation of inducible HSP70 proteins. We further provide evidence
      that the cochaperone BAG2 contributes to HSP70 stabilization in tissues other
      than testes. Our findings reveal that chaperone expression is determined not only
      by regulated transcription, but also by controlled degradation, with degradation
      inhibiting cochaperones exerting essential prosurvival functions. 

PMID- 24899642
TI  - Effect of M1a and M1b category in metastatic colorectal cancer.
AB  - BACKGROUND: In 2009, the American Joint Committee on Cancer version 7 staging
      system introduced the M1 subclassifications M1a (single metastatic site) and M1b
      (peritoneal or multiple metastatic sites). The study objectives were to evaluate
      the prognostic effect of site of metastasis and M1a/b category among patients
      with newly diagnosed colorectal cancer and synchronous metastasis. PATIENTS AND
      METHODS: Patients with newly diagnosed pathologic or clinical category M1
      colorectal cancer referred to the British Columbia Cancer Agency between 1999 and
      2007 were included. Demographic, tumor, treatment, and outcome data were
      prospectively collected, and prognostic factors were identified. Univariate Cox
      models were used to assess the prognostic impact of individual sites of
      metastasis and to determine the effect of M1a/b category on overall survival
      (OS). RESULTS: Among 2,049 eligible patients, 70% had M1a and 30% M1b category
      disease. The most common sites of common single sites of metastasis included
      liver (56%), lung (5.3%), and peritoneum (3.6%). Metastasis to a single organ or
      site, including peritoneum, was associated with improved OS compared with
      multiple sites of metastasis. In multivariate analysis, M1b category conferred
      inferior survival and hazard ratio (HR) 1.38 (95% confidence interval [CI]: 1.22,
      1.55), along with age >70 and Eastern Cooperative Oncology Group performance
      status of 3-4. Resection of primary tumor was associated with improved survival,
      HR 0.46 (95% CI: 0.41, 0.52). Results were similar in subgroup analysis of
      patients undergoing resection of their primary tumor when histology, tumor, and
      node category were included. CONCLUSION: The results lend support to the
      introduction of M1a/b colorectal cancer categories. Consideration may be given to
      classifying patients with solitary peritoneal metastasis only as M1a rather than
      M1b category. Further refinement of category M1a to reflect resectability of
      metastasis at initial diagnosis may improve prognostication.

PMID- 24899641
TI  - OS-9 facilitates turnover of nonnative GRP94 marked by hyperglycosylation.
AB  - The tight coupling of protein folding pathways with disposal mechanisms promotes
      the efficacy of protein production in the endoplasmic reticulum (ER). It has been
      hypothesized that the ER-resident molecular chaperone glucose-regulated protein
      94 (GRP94) is part of this quality control coupling because it supports folding
      of select client proteins yet also robustly associates with the lectin
      osteosarcoma amplified 9 (OS-9), a component involved in ER-associated
      degradation (ERAD). To explore this possibility, we investigated potential
      functions for the GRP94/OS-9 complex in ER quality control. Unexpectedly, GRP94
      does not collaborate with OS-9 in ERAD of misfolded substrates, nor is the
      chaperone required directly for OS-9 folding. Instead, OS-9 binds preferentially
      to a subpopulation of GRP94 that is hyperglycosylated on cryptic N-linked glycan
      acceptor sites. Hyperglycosylated GRP94 forms have nonnative conformations and
      are less active. As a result, these species are degraded much faster than the
      major, monoglycosylated form of GRP94 in an OS-9-mediated, ERAD-independent,
      lysosomal-like mechanism. This study therefore clarifies the role of the GRP94/OS
      9 complex and describes a novel pathway by which glycosylation of cryptic
      acceptor sites influences the function and fate of an ER-resident chaperone. 

PMID- 24899643
TI  - The challenging world of cytopenias: distinguishing myelodysplastic syndromes
      from other disorders of marrow failure.
AB  - Over the past decade, our understanding of bone marrow failure has advanced
      considerably. Marrow failure encompasses multiple overlapping diseases, and there
      is increasing availability of diagnostic tools to distinguish among the subtypes.
      Identification of genetic alterations that underlie marrow failure has also
      greatly expanded, especially for myelodysplastic syndromes. Molecular markers are
      increasingly used to guide the management of myelodysplasia and may distinguish
      this diagnosis from other marrow failure disorders. This review summarizes the
      current state of distinguishing among causes of marrow failure and discusses the
      potential uses of multiple diagnostic and prognostic indicators in the management
      of myelodysplastic syndromes and other bone marrow failure disorders. 

PMID- 24899644
TI  - Adolescents and young adults with a "rare" cancer: getting past semantics to
      optimal care for patients with germ cell tumors.

PMID- 24899645
TI  - Seizure prognosis in brain tumors: new insights and evidence-based management.
AB  - Brain tumor-related epilepsy (BTE) is common in low- and high-grade gliomas. The
      risk of seizures varies between 60% and 100% among low-grade gliomas and between
      40% and 60% in glioblastomas. The presence of seizures in patients with brain
      tumors implies favorable and unfavorable factors. New-onset seizures represent an
      early warning sign for the presence of a brain tumor and count as a good
      prognostic factor for survival. Recurrence or worsening of seizures during the
      course of disease may signal tumor progression. Each of the modalities for tumor
      control (i.e., surgery, radiotherapy, chemotherapy) contributes to seizure
      control. Nevertheless, one third of BTE shows pharmacoresistance to antiepileptic
      drugs (AEDs) and may severely impair the burden of living with a brain tumor. For
      symptomatic therapy of BTE, seizure type and individual patient factors determine
      the appropriate AED. Randomized controlled trials in partial epilepsy in adults
      to which type BTE belongs and additional studies in gliomas indicate that
      levetiracetam is the agent of choice, followed by valproic acid (VPA). In the
      case of recurring seizures, combining these two drugs (polytherapy) seems
      effective and possibly synergistic. If either one is not effective or not well
      tolerated, lacosamide, lamotrigine, or zonisamide are additional options. A new
      and exciting insight is the potential contribution of VPA to prolonged survival,
      particularly in glioblastomas. A practice guideline on symptomatic medical
      management including dose schedules of AEDs is supplied. 

PMID- 24899650
TI  - Benefits and harms in clinical trials of duloxetine for treatment of major
      depressive disorder: comparison of clinical study reports, trial registries, and
      publications.
AB  - OBJECTIVE: To determine, using research on duloxetine for major depressive
      disorder as an example, if there are inconsistencies between protocols, clinical
      study reports, and main publicly available sources (journal articles and trial
      registries), and within clinical study reports themselves, with respect to
      benefits and major harms. DESIGN: Data on primary efficacy analysis and major
      harms extracted from each data source and compared. SETTING: Nine randomised
      placebo controlled trials of duloxetine (total 2878 patients) submitted to the
      European Medicines Agency (EMA) for marketing approval for major depressive
      disorder. DATA SOURCES: Clinical study reports, including protocols as appendices
      (total 13,729 pages), were obtained from the EMA in May 2011. Journal articles
      were identified through relevant literature databases and contacting the
      manufacturer, Eli Lilly. Clinicaltrials.gov and the manufacturer's online
      clinical trial registry were searched for trial results. RESULTS: Clinical study
      reports fully described the primary efficacy analysis and major harms (deaths
      (including suicides), suicide attempts, serious adverse events, and
      discontinuations because of adverse events). There were minor inconsistencies in
      the population in the primary efficacy analysis between the protocol and clinical
      study report and within the clinical study report for one trial. Furthermore, we
      found contradictory information within the reports for seven serious adverse
      events and eight adverse events that led to discontinuation but with no apparent
      bias. In each trial, a median of 406 (range 177-645) and 166 (100-241) treatment
      emergent adverse events (adverse events that emerged or worsened after study drug
      was started) in the randomised phase were not reported in journal articles and
      Lilly trial registry reports, respectively. We also found publication bias in
      relation to beneficial effects. CONCLUSION: Clinical study reports contained
      extensive data on major harms that were unavailable in journal articles and in
      trial registry reports. There were inconsistencies between protocols and clinical
      study reports and within clinical study reports. Clinical study reports should be
      used as the data source for systematic reviews of drugs, but they should first be
      checked against protocols and within themselves for accuracy and consistency.

PMID- 24899652
TI  - Gwen Adshead: Posing as a florist.

PMID- 24899651
TI  - Coding of adverse events of suicidality in clinical study reports of duloxetine
      for the treatment of major depressive disorder: descriptive study.
AB  - OBJECTIVE: To assess the effects of coding and coding conventions on summaries
      and tabulations of adverse events data on suicidality within clinical study
      reports. DESIGN: Systematic electronic search for adverse events of suicidality
      in tables, narratives, and listings of adverse events in individual patients
      within clinical study reports. Where possible, for each event we extracted the
      original term reported by the investigator, the term as coded by the medical
      coding dictionary, medical coding dictionary used, and the patient's trial
      identification number. Using the patient's trial identification number, we
      attempted to reconcile data on the same event between the different formats for
      presenting data on adverse events within the clinical study report. SETTING: 9
      randomised placebo controlled trials of duloxetine for major depressive disorder
      submitted to the European Medicines Agency for marketing approval. DATA SOURCES:
      Clinical study reports obtained from the EMA in 2011. RESULTS: Six trials used
      the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse
      Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory
      Activities). Suicides were clearly identifiable in all formats of adverse event
      data in clinical study reports. Suicide attempts presented in tables included
      both definitive and provisional diagnoses. Suicidal ideation and preparatory
      behaviour were obscured in some tables owing to the lack of specificity of the
      medical coding dictionary, especially COSTART. Furthermore, we found one event of
      suicidal ideation described in narrative text that was absent from tables and
      adverse event listings of individual patients. The reason for this is unclear,
      but may be due to the coding conventions used. CONCLUSION: Data on adverse events
      in tables in clinical study reports may not accurately represent the underlying
      patient data because of the medical dictionaries and coding conventions used. In
      clinical study reports, the listings of adverse events for individual patients
      and narratives of adverse events can provide additional information, including
      original investigator reported adverse event terms, which can enable a more
      accurate estimate of harms.

PMID- 24899653
TI  - Campylobacter fetus subsp. testudinum subsp. nov., isolated from humans and
      reptiles.
AB  - A polyphasic study was undertaken to determine the taxonomic position of 13
      Campylobacter fetus-like strains from humans (n = 8) and reptiles (n = 5). The
      results of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)
      MS and genomic data from sap analysis, 16S rRNA gene and hsp60 sequence
      comparison, pulsed-field gel electrophoresis, amplified fragment length
      polymorphism analysis, DNA-DNA hybridization and whole genome sequencing
      demonstrated that these strains are closely related to C. fetus but clearly
      differentiated from recognized subspecies of C. fetus. Therefore, this unique
      cluster of 13 strains represents a novel subspecies within the species C. fetus,
      for which the name Campylobacter fetus subsp. testudinum subsp. nov. is proposed,
      with strain 03-427(T) ( = ATCC BAA-2539(T) = LMG 27499(T)) as the type strain.
      Although this novel taxon could not be differentiated from C. fetus subsp. fetus
      and C. fetus subsp. venerealis using conventional phenotypic tests, MALDI-TOF MS
      revealed the presence of multiple phenotypic biomarkers which distinguish
      Campylobacter fetus subsp. testudinum subsp. nov. from recognized subspecies of
      C. fetus. 

PMID- 24899654
TI  - Aestuariivita boseongensis gen. nov., sp. nov., isolated from a tidal flat
      sediment.
AB  - A Gram-stain-negative, aerobic, non-motile and coccoid, ovoid or rod-shaped
      bacterial strain, BS-B2(T), which was isolated from a tidal flat sediment at
      Boseong in South Korea, was characterized taxonomically. Strain BS-B2(T) grew
      optimally at 30  degrees C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v)
      NaCl. The novel strain exhibited highest 16S rRNA gene sequence similarity (97.4
      %) to Marivita geojedonensis DPG-138(T). Neighbour-joining, maximum-likelihood
      and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences
      revealed that strain BS-B2(T) is closely related to Primorskyibacter sedentarius
      KMM 9018(T), showing 96.5 % sequence similarity. Strain BS-B2(T) contained Q-10
      as the predominant ubiquinone and C18 : 1omega7c as the predominant fatty acid.
      The polar lipid profile of strain BS-B2(T) comprised phosphatidylcholine,
      phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid as
      major components, and differentiated it from the type strains of P. sedentarius
      and M. geojedonensis. The DNA G+C content of strain BS-B2(T) was 62.2 mol%.
      Differential phenotypic properties, together with the phylogenetic and
      chemotaxonomic data, demonstrated that strain BS-B2(T) can be distinguished from
      phylogenetically related genera as well as P. sedentarius and M. geojedonensis.
      On the basis of the data presented, strain BS-B2(T) is considered to represent a
      novel species of a new genus, for which the name Aestuariivita boseongensis gen.
      nov., sp. nov. is proposed. The type strain of Aestuariivita boseongensis is BS
      B2(T) ( = KCTC 42052(T) = CECT 8532(T)). 

PMID- 24899655
TI  - Lactobacillus sicerae sp. nov., a lactic acid bacterium isolated from Spanish
      natural cider.
AB  - Strains CUPV261(T) and CUPV262 were isolated from ropy natural ciders of the
      Basque Country, Spain, in 2007. Cells are Gram-stain positive, non-spore-forming,
      motile rods, facultative anaerobes and catalase-negative. The strains are
      obligately homofermentative (final product dl-lactate) and produce
      exopolysaccharides from sucrose. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that the highest similarity to both isolates corresponded to
      the type strain of Lactobacillus vini (99.1 %), followed by Lactobacillus
      satsumensis (96.4 %), and Lactobacillus oeni (96.2 %), and for all other
      established species, 16S rRNA gene sequence similarities were below 96 %. The
      species delineation of strains CUPV261(T) and CUPV262 was evaluated through RAPD
      fingerprinting. In addition, a random partial genome pyrosequencing approach was
      performed on strain CUPV261(T) in order to compare it with the genome sequence of
      Lactobacillus vini DSM 20605(T) and calculate indexes of average nucleotide
      identity (ANI) between them. Results permit the conclusion that strains
      CUPV261(T) and CUPV262 represent a novel species of the genus Lactobacillus, for
      which the name Lactobacillus sicerae sp. nov. is proposed. The type strain is
      CUPV261(T) ( = CECT 8227(T) = KCTC 21012(T)). 

PMID- 24899657
TI  - Rhizobium straminoryzae sp. nov., isolated from the surface of rice straw.
AB  - An aerobic, Gram-stain-negative, rod-shaped bacterium, designated strain CC
      LY845(T), was isolated from the surface of rice straw in Taiwan. Cells were non
      motile, and no flagellum was detected. Comparison of 16S rRNA gene sequences
      indicated that the strain was phylogenetically related to species of the genus
      Rhizobium, with closest similarity to Rhizobium pseudoryzae KCTC 23294(T) (97.6
      %), R. rhizoryzae KCTC 23652(T) (97.0 %) and R. oryzae LMG 24253(T) (96.7 %);
      other species showed lower levels of similarity (<96.6 %). The DNA-DNA
      relatedness of strain CC-LY845(T) and R. pseudoryzae KCTC 23294(T) was 34.8+/-3.1
      % (reciprocal value 39.2+/-2.2 %). Phylogenetic analysis based on the
      housekeeping atpD and recA genes showed that the novel strain could be
      distinguished from R. pseudoryzae KCTC 23294(T) (92.7 and 91.5 %, respectively)
      and other species of the genus Rhizobium. The temperature range for growth was 25
      42  degrees C, the pH range was 5.0-9.0 and NaCl concentrations up to 4.0 % (w/v)
      were tolerated. Strain CC-LY845(T) did not form nodules on four different
      legumes, and the nodD and nifH genes were not detected by PCR. The major fatty
      acids were C16 : 0 and summed feature 8 (C18 : 1omega7c/C18 : 1omega6c). The
      polyamine pattern of strain CC-LY845(T) showed spermidine and putrescine as major
      polyamines. The predominant quinone system was ubiquinone 10 (Q-10). The DNA G+C
      content was 68.3+/-2.4 mol%. Base on its phylogenetic, phenotypic and
      chemotaxonomic features, strain CC-LY845(T) is proposed to represent a novel
      species within the genus Rhizobium, for which the name Rhizobium straminoryzae
      sp. nov. is proposed. The type strain is strain CC-LY845(T) ( = BCRC 80698(T) =
      JCM 19536(T)). 

PMID- 24899656
TI  - Dysgonomonas macrotermitis sp. nov., isolated from the hindgut of a fungus
      growing termite.
AB  - A Gram-stain-negative, facultatively anaerobic, non-motile and coccoid- to short
      rod-shaped bacterium, designated strain Dys-CH1(T), was isolated from the hindgut
      of a fungus-growing termite Macrotermes barneyi. The optimal pH and cultivation
      temperature of strain Dys-CH1(T) were pH 7.2-7.6 and 35-37  degrees C,
      respectively. Sequence analysis of 16S rRNA gene showed that Dys-CH1(T) shared
      94.6 % and 90.9 % similarity with Dysgonomonas capnocytophagoides JCM 16697(T)
      and Dysgonomonas gadei CCUG 42882(T), respectively. Strain Dys-CH1(T) was found
      to be different from other species of the genus Dysgonomonas with validly
      published names with respect to taxonomically important traits, including
      habitat, biochemical tests, DNA G+C content, bile resistance, fatty-acid
      composition and susceptibility to antimicrobial agents. On the basis of these
      characteristics, strain Dys-CH1(T) represents a novel species of the genus
      Dysgonomonas for which the name Dysgonomonas macrotermitis sp. nov. is proposed.
      The type strain is Dys-CH1(T) ( = JCM 19375(T) = DSM 27370(T)). 

PMID- 24899658
TI  - Acetobacteroides hydrogenigenes gen. nov., sp. nov., an anaerobic hydrogen
      producing bacterium in the family Rikenellaceae isolated from a reed swamp.
AB  - A strictly anaerobic, mesophilic, carbohydrate-fermenting, hydrogen-producing
      bacterium, designated strain RL-C(T), was isolated from a reed swamp in China.
      Cells were Gram-stain-negative, catalase-negative, non-spore-forming, non-motile
      rods measuring 0.7-1.0 um in width and 3.0-8.0 um in length. The optimum
      temperature for growth of strain RL-C(T) was 37  degrees C (range 25-40  degrees
      C) and pH 7.0-7.5 (range pH 5.7-8.0). The strain could grow fermentatively on
      yeast extract, tryptone, arabinose, glucose, galactose, mannose, maltose,
      lactose, glycogen, pectin and starch. The main end products of glucose
      fermentation were acetate, H2 and CO2. Organic acids, alcohols and amino acids
      were not utilized for growth. Yeast extract was not required for growth; however,
      it stimulated growth slightly. Nitrate, sulfate, sulfite, thiosulfate, elemental
      sulfur and Fe(III) nitrilotriacetate were not reduced as terminal electron
      acceptors. Aesculin was hydrolysed but not gelatin. Indole and H2S were produced
      from yeast extract. The G+C content of the genomic DNA was 51.2 mol%. The major
      cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and C16 : 0. The most
      abundant polar lipid of strain RL-C(T) was phosphatidylethanolamine. 16S rRNA
      gene sequence analysis revealed that the isolate belongs to the uncultured
      Blvii28 wastewater-sludge group (http://www.arb-silva.de/) in the family
      Rikenellaceae of the phylum Bacteroidetes, and shared low sequence similarities
      with the related species Alistipes shahii WAL 8301(T) (81.8 %), Rikenella
      microfusus ATCC 29728(T) (81.7 %) and Anaerocella delicata WN081(T) (80.9 %). On
      the basis of these data, a novel species in a new genus of the family
      Rikenellaceae is proposed, Acetobacteroides hydrogenigenes gen. nov., sp. nov.
      The type strain of the type species is RL-C(T) ( = JCM 17603(T) = DSM 24657(T) =
      CGMCC 1.5173(T)). 

PMID- 24899659
TI  - Oceanicola antarcticus sp. nov. and Oceanicola flagellatus sp. nov., moderately
      halophilic bacteria isolated from seawater.
AB  - Two Gram-stain-negative, aerobic, moderately halophilic, rod-shaped bacteria
      (strains Ar-45(T) and DY470(T)) were isolated from seawater collected from the
      Southern Ocean and the Pacific Ocean, respectively. Growth of strain Ar-45(T) was
      observed with between 0.5 and 10.0 % (w/v) NaCl (optimally with 0.5-3.0 %) and
      between pH 5.5 and 9.5. Strain DY470(T) grew in the presence of 0.5-7.5 % (w/v)
      NaCl (optimally with 2.0 %) and at pH 5.5-8.5. Chemotaxonomic analysis showed Q
      10 as the respiratory quinone for both strains. The major fatty acids (>5 %) of
      strain Ar-45(T) were C16 : 0, C19 : 0 cyclo omega8c and C18 : 1omega7c, while
      those of strain DY470(T) were C18 : 1omega7c, C16 : 0 and 11-methyl C18 :
      1omega7c. The DNA G+C contents of the two strains were 62.0 and 61.8 mol%,
      respectively. Phylogenetic analyses based on 16S rRNA gene sequences showed that
      strains Ar-45(T) and DY470(T) were related most closely to the genus Oceanicola,
      with sequence similarities of 97.4-94.0 and 97.7-94.7 %, respectively. The DNA
      DNA hybridization value between strain Ar-45(T) and Oceanicola marinus LMG
      23705(T) was 22.0 %. Levels of DNA-DNA relatedness between strain DY470(T) and
      Oceanicola nitratireducens LMG 24663(T) and Oceanicola batsensis DSM 15984(T)
      were 32.5 and 26.1 %, respectively. Based on phylogenetic, chemotaxonomic and
      phenotypic data, strains Ar-45(T) and DY470(T) are considered to represent two
      novel species of the genus Oceanicola, for which the names Oceanicola antarcticus
      (type strain Ar-45(T) = CGMCC 1.12662(T) = LMG 27868(T)) and Oceanicola
      flagellatus (type strain DY470(T) = CGMCC 1.12664(T) = LMG 27871(T)) are
      proposed. 

PMID- 24899660
TI  - Is the risk of tumour necrosis factor inhibitor-induced lupus or lupus-like
      syndrome the same with monoclonal antibodies and soluble receptor? A case/non
      case study in a nationwide pharmacovigilance database.
AB  - OBJECTIVE: Each TNF-alpha inhibitor (TNFi) can induce lupus or lupus-like
      syndrome. Nevertheless, the risk may differ between drugs because of different
      apoptosis induction properties. The aim of this study was to assess the putative
      association of each TNFi with lupus or lupus-like-syndrome. METHODS: All
      spontaneous reports of TNFi-related lupus recorded in the French
      pharmacovigilance database between January 2000 and December 2012 were described.
      We conducted disproportionality analyses (case/non-case method) to assess the
      link between TNFi and lupus, calculating reporting odds ratios (RORs). We used
      isoniazid as positive control and acetaminophen as negative control. We performed
      sensitivity analyses to test for event-related and drug-related competition
      biases. RESULTS: Among 309 671 spontaneous reports, 5213 involved TNFi. Among
      these, 39 were lupus or lupus-like syndromes: 25 involved infliximab, 9
      adalimumab and 5 etanercept. The male:female sex ratio was 0.1 and the mean age
      was 44.9 years. Among the 39 cases, 28% fulfilled at least four ACR criteria for
      SLE. Median time to lupus onset was 11 months. Cutaneous and rheumatological
      involvement were the most frequent. Antinuclear autoantibodies were present in
      all patients, with anti-DNA specificity in 77.8%. Improvement was observed after
      TNFi withdrawal. There was a significant association between TNFi and lupus (ROR
      = 7.72, 95% CI 5.50, 10.83). The ROR was similar for infliximab (10.97, 95% CI
      7.27, 16.56) and adalimumab (9.03, 95% CI 4.64, 17.58) and was 4.02 (95% CI 1.66,
      9.75) for etanercept. Sensitivity analyses led to similar results. CONCLUSION:
      Although CIs overlap, there is a clear trend towards a decreased risk with
      etanercept compared with monoclonal TNFis.

PMID- 24899661
TI  - Increased plasma lactoferrin levels in leucocytapheresis therapy in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to clarify the mechanism of
      leucocytapheresis (LCAP) in patients with RA. METHODS: Protein profiles of blood
      samples from two patients with RA obtained via LCAP column inlet and outlet lines
      were analysed by two-dimensional fluorescence difference gel electrophoresis and
      mass spectrometry. The lactoferrin (LTF) levels of peripheral and circulating
      blood samples from seven patients obtained via the LCAP column blood circuit were
      then determined by ELISA. Peripheral blood samples from 14 patients with RA were
      exposed to unwoven polyester fibre filters and the LTF level was determined. In
      addition, morphological changes in neutrophils after exposure to the filter were
      examined by optical microscopy, electronic microscopy and LTF immunostaining.
      RESULTS: LTF levels were increased in both samples from the LCAP column outlet
      and peripheral blood at the end of LCAP treatment. Furthermore, peripheral blood
      samples exposed to the filter revealed a decreased number of neutrophils and an
      increased level of LTF. Morphological analysis of the exposed neutrophils showed
      vacuolization of the cytoplasm and degranulation of LTF-positive granules. These
      data suggest that LTF stored in the granules of neutrophils is released from the
      neutrophils caught in the LCAP column. CONCLUSION: Because LTF has been reported
      to have multiple anti-inflammatory properties, increased levels of LTF may
      contribute to the clinical effect of LCAP in patients with RA.

PMID- 24899663
TI  - Hypersensitivity reactions to tocilizumab: role of skin tests in diagnosis.

PMID- 24899662
TI  - Myeloperoxidase and oxidation of uric acid in gout: implications for the clinical
      consequences of hyperuricaemia.
AB  - OBJECTIVES: The aims of this study were to establish whether, in patients with
      gout, MPO is released from neutrophils and urate is oxidized to allantoin and if
      these effects are attenuated by allopurinol. METHODS: MPO, urate, allantoin and
      oxypurinol were measured in plasma from 54 patients with gout and 27 healthy
      controls. Twenty-three patients had acute gout, 13 of whom were receiving
      allopurinol, and 31 had intercritical gout, 20 of whom were receiving
      allopurinol. Ten additional gout patients had samples collected before and after
      4 weeks of allopurinol. RESULTS: Plasma MPO and its specific activity were higher
      (P < 0.05) in patients with acute gout not receiving allopurinol compared with
      controls. MPO protein in patients' plasma was related to urate concentration (r =
      0.5, P < 0.001). Plasma allantoin was higher (P < 0.001) in all patient groups
      compared with controls. In controls and patients not receiving allopurinol,
      allantoin was associated with plasma urate (r = 0.62, P < 0.001) and MPO activity
      (r = 0.45, P < 0.002). When 10 patients were treated with allopurinol, it lowered
      their plasma urate and allantoin (P = 0.002). In all patients receiving
      allopurinol, plasma allantoin was related to oxypurinol (r = 0.65, P < 0.0001).
      Oxypurinol was a substrate for purified MPO that enhanced the oxidation of urate.
      CONCLUSION: Increased concentrations of urate in gout lead to the release of MPO
      from neutrophils and the oxidation of urate. Products of MPO and reactive
      metabolites of urate may contribute to the pathology of gout and hyperuricaemia.
      At low concentrations, oxypurinol should reduce inflammation, but high
      concentrations may contribute to oxidative stress.

PMID- 24899664
TI  - Efficacy of pamidronate therapy in children with chronic non-bacterial osteitis:
      disease activity assessment by whole body magnetic resonance imaging.
AB  - OBJECTIVE: The aim of this study was to describe the efficacy of pamidronate
      therapy on disease activity in children with chronic non-bacterial osteitis (CNO)
      using whole body MRI (WB-MRI). METHODS: Clinical assessment and WB-MRI were
      obtained in 11 children before and after 1 year of pamidronate therapy using a
      1.5 T MRI scanner and short tau inversion recovery sequences. The images were
      reported by a paediatric radiologist. RESULTS: WB-MRI identified 75 lesions in 11
      patients; 16 of these lesions had not been detected by clinical examination.
      Follow-up MRI after 1 year of pamidronate showed complete resolution of
      inflammation in 45 lesions, moderate improvement in 10 lesions and no change in
      20 lesions. Two new lesions developed while on treatment. CONCLUSION: WB-MRI
      allows a more accurate assessment of the disease extent in CNO than clinical
      examination alone and is useful in the objective measurement of treatment
      efficacy. Pamidronate appears to be an effective treatment in children with CNO
      unresponsive to NSAIDs.

PMID- 24899665
TI  - Limited utility of residue masking for positive-selection inference.
AB  - Errors in multiple sequence alignments (MSAs) can reduce accuracy in positive
      selection inference. Therefore, it has been suggested to filter MSAs before
      conducting further analyses. One widely used filter, Guidance, allows users to
      remove MSA positions aligned with low confidence. However, Guidance's utility in
      positive-selection inference has been disputed in the literature. We have
      conducted an extensive simulation-based study to characterize fully how Guidance
      impacts positive-selection inference, specifically for protein-coding sequences
      of realistic divergence levels. We also investigated whether novel scoring
      algorithms, which phylogenetically corrected confidence scores, and a new gap
      penalization score-normalization scheme improved Guidance's performance. We found
      that no filter, including original Guidance, consistently benefitted positive
      selection inferences. Moreover, all improvements detected were exceedingly
      minimal, and in certain circumstances, Guidance-based filters worsened
      inferences. 

PMID- 24899666
TI  - Genome scans for detecting footprints of local adaptation using a Bayesian factor
      model.
AB  - There is a considerable impetus in population genomics to pinpoint loci involved
      in local adaptation. A powerful approach to find genomic regions subject to local
      adaptation is to genotype numerous molecular markers and look for outlier loci.
      One of the most common approaches for selection scans is based on statistics that
      measure population differentiation such as FST. However, there are important
      caveats with approaches related to FST because they require grouping individuals
      into populations and they additionally assume a particular model of population
      structure. Here, we implement a more flexible individual-based approach based on
      Bayesian factor models. Factor models capture population structure with latent
      variables called factors, which can describe clustering of individuals into
      populations or isolation-by-distance patterns. Using hierarchical Bayesian
      modeling, we both infer population structure and identify outlier loci that are
      candidates for local adaptation. In order to identify outlier loci, the
      hierarchical factor model searches for loci that are atypically related to
      population structure as measured by the latent factors. In a model of population
      divergence, we show that it can achieve a 2-fold or more reduction of false
      discovery rate compared with the software BayeScan or with an FST approach. We
      show that our software can handle large data sets by analyzing the single
      nucleotide polymorphisms of the Human Genome Diversity Project. The Bayesian
      factor model is implemented in the open-source PCAdapt software. 

PMID- 24899669
TI  - Mitochondrial donation is "not unsafe," review confirms.

PMID- 24899667
TI  - Evolutionary insights into premetazoan functions of the neuronal protein homer.
AB  - Reconstructing the evolution and ancestral functions of synaptic proteins
      promises to shed light on how neurons first evolved. The postsynaptic density
      (PSD) protein Homer scaffolds membrane receptors and regulates Ca(2+) signaling
      in diverse metazoan cell types (including neurons and muscle cells), yet its
      ancestry and core functions are poorly understood. We find that the protein
      domain organization and essential biochemical properties of metazoan Homer
      proteins, including their ability to tetramerize, are conserved in the
      choanoflagellate Salpingoeca rosetta, one of the closest living relatives of
      metazoans. Unlike in neurons, Homer localizes to the nucleoplasm in S. rosetta
      and interacts directly with Flotillin, a protein more commonly associated with
      cell membranes. Surprisingly, we found that the Homer/Flotillin interaction and
      its localization to the nucleus are conserved in metazoan astrocytes. These
      findings suggest that Homer originally interacted with Flotillin in the nucleus
      of the last common ancestor of metazoans and choanoflagellates and was later co
      opted to function as a membrane receptor scaffold in the PSD. 

PMID- 24899670
TI  - Computation of object approach by a system of visual motion-sensitive neurons in
      the crab Neohelice.
AB  - Similar to most visual animals, crabs perform proper avoidance responses to
      objects directly approaching them. The monostratified lobula giant neurons of
      type 1 (MLG1) of crabs constitute an ensemble of 14-16 bilateral pairs of motion
      detecting neurons projecting from the lobula (third optic neuropile) to the
      midbrain, with receptive fields that are distributed over the extensive visual
      field of the animal's eye. Considering the crab Neohelice (previously
      Chasmagnathus) granulata, here we describe the response of these neurons to
      looming stimuli that simulate objects approaching the animal on a collision
      course. We found that the peak firing time of MLG1 acts as an angular threshold
      detector signaling, with a delay of delta = 35 ms, the time at which an object
      reaches a fixed angular threshold of 49 degrees . Using in vivo intracellular
      recordings, we detected the existence of excitatory and inhibitory synaptic
      currents that shape the neural response. Other functional features identified in
      the MLG1 neurons were phasic responses at the beginning of the approach, a
      relation between the stimulus angular velocity and the excitation delay, and a
      mapping between membrane potential and firing frequency. Using this information,
      we propose a biophysical model of the mechanisms that regulate the encoding of
      looming stimuli. Furthermore, we found that the parameter encoded by the MLG1
      firing frequency during the approach is the stimulus angular velocity. The
      proposed model fits the experimental results and predicts the neural response to
      a qualitatively different stimulus. Based on these and previous results, we
      propose that the MLG1 neuron system acts as a directional coding system for
      collision avoidance. 

PMID- 24899668
TI  - Simultaneous Bayesian estimation of alignment and phylogeny under a joint model
      of protein sequence and structure.
AB  - For sequences that are highly divergent, there is often insufficient information
      to infer accurate alignments, and phylogenetic uncertainty may be high. One way
      to address this issue is to make use of protein structural information, since
      structures generally diverge more slowly than sequences. In this work, we extend
      a recently developed stochastic model of pairwise structural evolution to
      multiple structures on a tree, analytically integrating over ancestral structures
      to permit efficient likelihood computations under the resulting joint sequence
      structure model. We observe that the inclusion of structural information
      significantly reduces alignment and topology uncertainty, and reduces the number
      of topology and alignment errors in cases where the true trees and alignments are
      known. In some cases, the inclusion of structure results in changes to the
      consensus topology, indicating that structure may contain additional information
      beyond that which can be obtained from sequences. We use the model to investigate
      the order of divergence of cytoglobins, myoglobins, and hemoglobins and observe a
      stabilization of phylogenetic inference: although a sequence-based inference
      assigns significant posterior probability to several different topologies, the
      structural model strongly favors one of these over the others and is more robust
      to the choice of data set. 

PMID- 24899671
TI  - Transposed firing activation of motor units.
AB  - Muscles are composed of groups of muscle fibers, called motor units, each
      innervated by a single motoneuron originating in the spinal cord. During constant
      or linearly varying voluntary force contractions, motor units are activated in a
      hierarchical order, with the earlier-recruited motor units having greater firing
      rates than the later-recruited ones. We found that this normal pattern of firing
      activation can be altered during oscillatory contractions where the force
      oscillates at frequencies >=2 Hz. During these high-frequency oscillations, the
      activation of the lower-threshold motor units effectively decreases and that of
      the higher-threshold motor units effectively increases. This transposition of
      firing activation provides means to activate higher-threshold motor units
      preferentially. Our results demonstrate that the hierarchical regulation of motor
      unit activation can be manipulated to activate specific motoneuron populations
      preferentially. This finding can be exploited to develop new forms of physical
      therapies and exercise programs that enhance muscle performance or that target
      the preferential atrophy of high-threshold motor units as a result of aging or
      motor disorders such as stroke and amyotrophic lateral sclerosis. 

PMID- 24899672
TI  - Disrupting information coding via block of 4-AP-sensitive potassium channels.
AB  - Recent interest has emerged on the role of intrinsic biophysical diversity in
      neuronal coding. An important question in neurophysiology is understanding which
      voltage-gated ion channels are responsible for this diversity and how variable
      expression or activity of one class of ion channels across neurons of a single
      type affects they way populations carry information. In mitral cells in the
      olfactory bulb of mice, we found that biophysical diversity was conferred in part
      by 4-aminopyridine (4-AP)-sensitive potassium channels and reduced following
      block of those channels. When populations of mitral cells were stimulated with
      identical inputs, the diversity exhibited in their output spike patterns reduced
      with the addition of 4-AP, decreasing the stimulus information carried by
      ensembles of 15 neurons from 437 +/- 15 to 397 +/- 19 bits/s. Decreases in
      information were due to reduction in the diversity of population spike patterns
      generated in response to different features of the stimulus, suggesting that the
      coding capacity of a population can be altered by changes in the function of
      single ion channel types. 

PMID- 24899673
TI  - Rapid prediction of biomechanical costs during action decisions.
AB  - When given a choice between actions that yield the same reward, we tend to prefer
      the one that requires the least effort. Recent studies have shown that humans are
      remarkably accurate at evaluating the effort of potential reaching actions and
      can predict the subtle energetic demand caused by the nonisotropic biomechanical
      properties of the arm. In the present study, we investigated the time course over
      which such information is computed and comes to influence decisions. Two
      independent approaches were used. First, subjects performed a reach decision task
      in which the time interval for deciding between two candidate reaching actions
      was varied from 200 to 800 ms. Second, we measured motor-evoked potential (MEPs)
      to single-pulse transcranial magnetic stimulation (TMS) over the primary motor
      cortex (M1) to probe the evolving decision at different times after stimulus
      presentation. Both studies yielded a consistent conclusion: that a prediction of
      the effort associated with candidate movements is computed very quickly and
      influences decisions within 200 ms after presentation of the candidate actions.
      Furthermore, whereas the MEPs measured 150 ms after stimulus presentation were
      well correlated with the choices that subjects ultimately made, later in the
      trial the MEP amplitudes were primarily related to the muscular requirements of
      the chosen movement. This suggests that corticospinal excitability (CSE)
      initially reflects a competition between candidate actions and later changes to
      reflect the processes of preparing to implement the winning action choice. 

PMID- 24899675
TI  - Biting intentions modulate digastric reflex responses to sudden unloading of the
      jaw.
AB  - Reflex responses in jaw-opening muscles can be evoked when a brittle object
      cracks between the teeth and suddenly unloads the jaw. We hypothesized that this
      reflex response is flexible and, as such, is modulated according to the
      instructed goal of biting through an object. Study participants performed two
      different biting tasks when holding a peanut half stacked on a chocolate piece
      between their incisors. In one task, they were asked to split the peanut half
      only (single-split task), and in the other task, they were asked to split both
      the peanut and the chocolate in one action (double-split task). In both tasks,
      the peanut split evoked a jaw-opening muscle response, quantified from
      electromyogram (EMG) recordings of the digastric muscle in a window 20-60 ms
      following peanut split. Consistent with our hypothesis, we found that the jaw
      opening muscle response in the single-split trials was about twice the size of
      the jaw-opening muscle response in the double-split trials. A linear model that
      predicted the jaw-opening muscle response on a single-trial basis indicated that
      task settings played a significant role in this modulation but also that the
      presplit digastric muscle activity contributed to the modulation. These findings
      demonstrate that, like reflex responses to mechanical perturbations in limb
      muscles, reflex responses in jaw muscles not only show gain-scaling but also are
      modulated by subject intent. 

PMID- 24899674
TI  - Normalization of neuronal responses in cortical area MT across signal strengths
      and motion directions.
AB  - Multiple visual stimuli are common in natural scenes, yet it remains unclear how
      multiple stimuli interact to influence neuronal responses. We investigated this
      question by manipulating relative signal strengths of two stimuli moving
      simultaneously within the receptive fields (RFs) of neurons in the extrastriate
      middle temporal (MT) cortex. Visual stimuli were overlapping random-dot patterns
      moving in two directions separated by 90 degrees . We first varied the motion
      coherence of each random-dot pattern and characterized, across the direction
      tuning curve, the relationship between neuronal responses elicited by
      bidirectional stimuli and by the constituent motion components. The tuning curve
      for bidirectional stimuli showed response normalization and can be accounted for
      by a weighted sum of the responses to the motion components. Allowing nonlinear,
      multiplicative interaction between the two component responses significantly
      improved the data fit for some neurons, and the interaction mainly had a
      suppressive effect on the neuronal response. The weighting of the component
      responses was not fixed but dependent on relative signal strengths. When two
      stimulus components moved at different coherence levels, the response weight for
      the higher-coherence component was significantly greater than that for the lower
      coherence component. We also varied relative luminance levels of two coherently
      moving stimuli and found that MT response weight for the higher-luminance
      component was also greater. These results suggest that competition between
      multiple stimuli within a neuron's RF depends on relative signal strengths of the
      stimuli and that multiplicative nonlinearity may play an important role in
      shaping the response tuning for multiple stimuli. 

PMID- 24899677
TI  - Corticospinal excitability of the biceps brachii is higher during arm cycling
      than an intensity-matched tonic contraction.
AB  - Human studies have not assessed corticospinal excitability of an upper-limb prime
      mover during arm cycling. The purpose of the present study was to determine
      whether supraspinal and/or spinal motoneuron excitability of the biceps brachii
      was different between arm cycling and an intensity-matched tonic contraction. We
      hypothesized that spinal motoneuron excitability would be higher during arm
      cycling than an intensity-matched tonic contraction. Supraspinal and spinal
      motoneuron excitability were assessed using transcranial magnetic stimulation
      (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the
      corticospinal tract, respectively. TMS-induced motor-evoked potentials (MEPs) and
      TMES-induced cervicomedullary-evoked potentials (CMEPs) were assessed at three
      separate positions (3, 6, and 12 o'clock relative to a clock face) during arm
      cycling and an intensity-matched tonic contraction. MEP amplitudes were 7.2 and
      8.8% maximum amplitude of the compound muscle action potential (Mmax) larger
      during arm cycling compared with a tonic contraction at the 3 (P < 0.001) and 6
      o'clock (P < 0.001) positions, respectively. There was no difference between
      tasks during elbow extension (12 o'clock). CMEP amplitudes were 5.2% Mmax larger
      during arm cycling compared with a tonic contraction at the 3 o'clock position (P
      < 0.001) with no differences seen at midflexion (6 o'clock) or extension (12
      o'clock). The data indicate an increase in the excitability of corticospinal
      neurons, which ultimately project to biceps brachii during the elbow flexion
      portion of arm cycling, and increased spinal motoneuron excitability at the onset
      of elbow flexion during arm cycling. We conclude that supraspinal and spinal
      motoneuron excitability are phase- and task-dependent. 

PMID- 24899676
TI  - Stabilization of cat paw trajectory during locomotion.
AB  - We investigated which of cat limb kinematic variables during swing of regular
      walking and accurate stepping along a horizontal ladder are stabilized by
      coordinated changes of limb segment angles. Three hypotheses were tested: 1)
      animals stabilize the entire swing trajectory of specific kinematic variables
      (performance variables); and 2) the level of trajectory stabilization is similar
      between regular and ladder walking and 3) is higher for forelimbs compared with
      hindlimbs. We used the framework of the uncontrolled manifold (UCM) hypothesis to
      quantify the structure of variance of limb kinematics in the limb segment
      orientation space across steps. Two components of variance were quantified for
      each potential performance variable, one of which affected it ("bad variance,"
      variance orthogonal to the UCM, VORT) while the other one did not ("good
      variance," variance within the UCM, VUCM). The analysis of five candidate
      performance variables revealed that cats during both locomotor behaviors
      stabilize 1) paw vertical position during the entire swing (VUCM > VORT, except
      in mid-hindpaw swing of ladder walking) and 2) horizontal paw position in initial
      and terminal swing (except for the entire forepaw swing of regular walking). We
      also found that the limb length was typically stabilized in midswing, whereas
      limb orientation was not (VUCM <= VORT) for both limbs and behaviors during
      entire swing. We conclude that stabilization of paw position in early and
      terminal swing enables accurate and stable locomotion, while stabilization of
      vertical paw position in midswing helps paw clearance. This study is the first to
      demonstrate the applicability of the UCM-based analysis to nonhuman movement. 

PMID- 24899679
TI  - RE: Cowden syndrome and PTEN hamartoma tumor syndrome: systematic review and
      revised diagnostic criteria.

PMID- 24899678
TI  - Change in hospital-level use of transradial percutaneous coronary intervention
      and periprocedural outcomes: insights from the national cardiovascular data
      registry.
AB  - BACKGROUND: Whether increasing use of radial access has improved percutaneous
      coronary intervention outcomes remains unknown. We sought to determine the
      relationship between increasing facility-level use of transradial percutaneous
      coronary intervention (TRI) and periprocedural outcomes. METHODS AND RESULTS:
      Within the National Cardiovascular Data Registry CathPCI Registry, we estimated
      the risk-adjusted association between hospital category of change in TRI use
      (during the 3-year period from 2009 to 2012) and trends in access site and
      overall bleeding, fluoroscopy time, and contrast use among 818 facilities with
      low baseline TRI use. There were 4 categories of hospital change in TRI use: very
      low (baseline, 0.2% increasing to 1.8% at the end of 3 years), low (0.9%
      increasing to 8.9%), moderate (1.6% increasing to 27.2%), and high (1.0%
      increasing to 45.1%). Risk-adjusted access site bleeding decreased over time for
      all hospital categories; however, the rate of decline varied across hospital
      categories (P for interaction, <0.001). The decrease in access site bleeding was
      significantly greater for hospitals with moderate or high increases in TRI use
      (relative risk, 0.45, 95% confidence interval, 0.36-0.56) when compared with that
      of very low or low hospitals (relative risk, 0.65; 95% confidence interval, 0.58
      0.74; P for comparison, 0.002). Similar findings were observed for overall
      bleeding. An increase in fluoroscopy time (~1.3 minutes) was noted at hospitals
      with moderate and high use of TRI (P=0.01). Trends in contrast use were similar
      across hospital categories. CONCLUSIONS: In a national sample of hospitals
      performing percutaneous coronary intervention, bleeding rates decreased over time
      for all hospital categories of change in TRI use. The decline in bleeding
      outcomes was larger at hospitals with increased adoption of TRI when compared
      with hospitals with minimal or no change in TRI use.

PMID- 24899680
TI  - Response.

PMID- 24899681
TI  - Rearing in a distorted magnetic field disrupts the 'map sense' of juvenile
      steelhead trout.
AB  - We used simulated magnetic displacements to test orientation preferences of
      juvenile steelhead trout (Oncorhynchus mykiss) exposed to magnetic fields
      existing at the northernmost and southernmost boundaries of their oceanic range.
      Fish reared in natural magnetic conditions distinguished between these two fields
      by orienting in opposite directions, with headings that would lead fish towards
      marine foraging grounds. However, fish reared in a spatially distorted magnetic
      field failed to distinguish between the experimental fields and were randomly
      oriented. The non-uniform field in which fish were reared is probably typical of
      fields that many hatchery fish encounter due to magnetic distortions associated
      with the infrastructure of aquaculture. Given that the reduced navigational
      abilities we observed could negatively influence marine survival, homing ability
      and hatchery efficiency, we recommend further study on the implications of
      rearing salmonids in unnatural magnetic fields. 

PMID- 24899682
TI  - Ancient DNA and the tropics: a rodent's tale.
AB  - Most genetic studies of Holocene fauna have been performed with ancient samples
      from dry and cold regions, in which preservation of fossils is facilitated and
      molecular damage is reduced. Ancient DNA work from tropical regions has been
      precluded owing to factors that limit DNA preservation (e.g. temperature,
      hydrolytic damage). We analysed ancient DNA from rodent jawbones identified as
      Ototylomys phyllotis, found in Holocene and Late Pleistocene stratigraphic layers
      from Loltun, a humid tropical cave located in the Yucatan peninsula. We extracted
      DNA and amplified six short overlapping fragments of the cytochrome b gene,
      totalling 666 bp, which represents an unprecedented success considering tropical
      ancient DNA samples. We performed genetic, phylogenetic and divergence time
      analyses, combining sequences from ancient and modern O. phyllotis, in order to
      assess the ancestry of the Loltun samples. Results show that all ancient samples
      fall into a unique clade that diverged prior to the divergence of the modern O.
      phyllotis, supporting it as a distinct Pleistocene form of the Ototylomys genus.
      Hence, this rodent's tale suggests that the sister group to modern O. phyllotis
      arose during the Miocene-Pliocene, diversified during the Pleistocene and went
      extinct in the Holocene. 

PMID- 24899683
TI  - Tree-hugging koalas demonstrate a novel thermoregulatory mechanism for arboreal
      mammals.
AB  - How climate impacts organisms depends not only on their physiology, but also
      whether they can buffer themselves against climate variability via their
      behaviour. One of the way species can withstand hot temperatures is by seeking
      out cool microclimates, but only if their habitat provides such refugia. Here, we
      describe a novel thermoregulatory strategy in an arboreal mammal, the koala
      Phascolarctos cinereus. During hot weather, koalas enhanced conductive heat loss
      by seeking out and resting against tree trunks that were substantially cooler
      than ambient air temperature. Using a biophysical model of heat exchange, we show
      that this behaviour greatly reduces the amount of heat that must be lost via
      evaporative cooling, potentially increasing koala survival during extreme heat
      events. While it has long been known that internal temperatures of trees differ
      from ambient air temperatures, the relevance of this for arboreal and semi
      arboreal mammals has not previously been explored. Our results highlight the
      important role of tree trunks as aboveground 'heat sinks', providing cool local
      microenvironments not only for koalas, but also for all tree-dwelling species. 

PMID- 24899684
TI  - Overexpression of DDX43 mediates MEK inhibitor resistance through RAS
      Upregulation in uveal melanoma cells.
AB  - The majority of uveal melanomas carry oncogenic mutations in the G proteins GNAQ
      and GNA11, with consequent activation of the MAPK pathway. Selective MEK
      inhibitors, such as selumetinib, have shown clinical benefit in uveal melanoma.
      However, mechanisms of drug resistance limit their efficacy in some patients.
      Analysis of MEK inhibitor-resistant uveal melanoma cell lines revealed the
      induction of RAS protein expression and activity. This effect was mediated by the
      RNA helicase DDX43, which was remarkably overexpressed in these cells. Depletion
      of DDX43 in MEK inhibitor-resistant cells decreased RAS proteins and inhibited
      ERK and AKT pathways. On the contrary, ectopic expression of DDX43 in parental
      uveal melanoma cells induced RAS protein levels and rendered cells resistant to
      MEK inhibition. Similar to DDX43 depletion, downregulation of KRAS, HRAS, and
      NRAS inhibited downstream pathways in the resistant cells, overcoming mutant GNAQ
      signaling. We also analyzed the expression of DDX43 in liver metastases of
      patients with uveal melanoma by RT-PCR, and found a significant overexpression of
      DDX43 in patients who did not benefit from selumetinib therapy. In conclusion,
      DDX43 induces RAS protein expression and signaling, mediating a novel mechanism
      of MEK inhibitor resistance. The detection of DDX43 in patients with uveal
      melanoma could lead to more targeted therapies for this disease.

PMID- 24899685
TI  - A novel small molecule aurora kinase inhibitor attenuates breast tumor-initiating
      cells and overcomes drug resistance.
AB  - Chemoresistance is a major cause of cancer treatment failure. Tumor-initiating
      cells (TIC) have attracted a considerable amount of attention due to their role
      in chemoresistance and tumor recurrence. Here, we evaluated the small molecule
      Aurora kinase inhibitor AKI603 as a novel agent against TICs in breast cancer.
      AKI603 significantly inhibited Aurora-A (AurA) kinase and induced cell-cycle
      arrest. In addition, the intragastric administration of AKI603 reduced xenograft
      tumor growth. Interestingly, we found that breast cancer cells that were
      resistant to epirubicin expressed a high level of activated AurA and also have a
      high CD24(Low)/CD44(High) TIC population. The inhibition of AurA kinase by AKI603
      abolished the epirubicin-induced enrichment of TICs. Moreover, AKI603 suppressed
      the capacity of cells to form mammosphere and also suppressed the expression of
      self-renewal genes (beta-catenin, c-Myc, Sox2, and Oct4). Thus, our work suggests
      the potential clinical use of the small molecule Aurora kinase inhibitor AKI603
      to overcome drug resistance induced by conventional chemotherapeutics in breast
      cancer.

PMID- 24899686
TI  - FAK Inhibition disrupts a beta5 integrin signaling axis controlling anchorage
      independent ovarian carcinoma growth.
AB  - Ovarian cancer ascites fluid contains matrix proteins that can impact tumor
      growth via integrin receptor binding. In human ovarian tumor tissue arrays, we
      find that activation of the cytoplasmic focal adhesion (FAK) tyrosine kinase
      parallels increased tumor stage, beta5 integrin, and osteopontin matrix staining.
      Elevated osteopontin, beta5 integrin, and FAK mRNA levels are associated with
      decreased serous ovarian cancer patient survival. FAK remains active within
      ovarian cancer cells grown as spheroids, and anchorage-independent growth
      analyses of seven ovarian carcinoma cell lines identified sensitive (HEY, OVCAR8)
      and resistant (SKOV3-IP, OVCAR10) cells to 0.1 MUmol/L FAK inhibitor (VS-4718,
      formerly PND-1186) treatment. VS-4718 promoted HEY and OVCAR8 G0-G1 cell-cycle
      arrest followed by cell death, whereas growth of SKOV3-IP and OVCAR10 cells was
      resistant to 1.0 MUmol/L VS-4718. In HEY cells, genetic or pharmacological FAK
      inhibition prevented tumor growth in mice with corresponding reductions in beta5
      integrin and osteopontin expression. beta5 knockdown reduced HEY cell growth in
      soft agar, tumor growth in mice, and both FAK Y397 phosphorylation and
      osteopontin expression in spheroids. FAK inhibitor-resistant (SKOV3-IP, OVCAR10)
      cells exhibited anchorage-independent Akt S473 phosphorylation, and expression of
      membrane-targeted and active Akt in sensitive cells (HEY, OVCAR8) increased
      growth but did not create a FAK inhibitor-resistant phenotype. These results link
      osteopontin, beta5 integrin, and FAK in promoting ovarian tumor progression.
      beta5 integrin expression may serve as a biomarker for serous ovarian carcinoma
      cells that possess active FAK signaling.

PMID- 24899688
TI  - Risk of end-stage renal disease and death after cardiovascular events in chronic
      kidney disease.
AB  - BACKGROUND: Patients with chronic kidney disease stages 3 to 5 (glomerular
      filtration rate <60 mL/min/1.73m(2)) are at increased risk of cardiovascular (CV)
      disease when compared with patients with less severe chronic kidney disease. How
      CV events modify the subsequent risk of progression to end-stage-renal disease
      (ESRD) or all-cause mortality (ACM) before ESRD is not well known. METHODS AND
      RESULTS: This retrospective cohort study involved 2964 chronic kidney disease
      subjects referred between January 2001 and December 2008 to the nephrology clinic
      at Sunnybrook Health Sciences Center, Toronto, Ontario. Interim CV events (heart
      failure, myocardial infarction, and stroke), ESRD, and ACM were ascertained from
      administrative data. Over a median follow-up time of 2.76 years (interquartile
      range, 1.45-4.62), 447 (15%) subjects had a CV event. In the same time period,
      318 (11%) developed ESRD, and 446 (15%) experienced ACM before ESRD (156 [5%]
      from a CV and 290 [10%] from a non-CV-related cause). When analyzed as a time
      dependent variable, an interim CV event was associated with a higher risk of
      subsequent ESRD (hazard ratio, 5.33; 95% confidence interval, 3.74-7.58) and ACM
      before ESRD (hazard ratio, 4.15, hazard ratio, 3.30-5.23). The hazard ratio for
      CV-related death versus non-CV-related death before ESRD was 12.38 (95%
      confidence interval, 8.30-18.45) versus 2.13 (95% confidence interval, 1.57
      2.87). CONCLUSIONS: CV events are common in patients with chronic kidney disease
      stages 3 to 5 and are associated with a substantial increase in the risk of ESRD
      and ACM before ESRD. Intensive primary and secondary prevention strategies may
      help attenuate this risk.

PMID- 24899687
TI  - Roles of deletion of Arid1a, a tumor suppressor, in mouse ovarian tumorigenesis.
AB  - The chromatin remodeling gene, ARID1A, has been implied as a tumor suppressor,
      and its somatic inactivating mutations occur in a wide variety of human cancers,
      most frequently in ovarian and uterine endometrioid and ovarian clear cell
      carcinomas. Tumors with ARID1A mutations also frequently harbor PTEN or PIK3CA
      mutations, suggesting their collaboration in tumorigenesis. Here, we used a
      conditional knockout mouse model in which Arid1a and Pten were deleted either
      individually or in combination in the mouse ovarian surface epithelium. After 6
      months, 59.1% of mice with Arid1a and Pten double knockout developed ovarian
      endometrioid or undifferentiated carcinoma, whereas the remaining mice showed
      hyperplasia of ovarian surface epithelium. In contrast, 52 mice with homozygous
      or heterozygous deletion in either Arid1a or Pten did not develop ovarian
      lesions. These results demonstrate that inactivation of Arid1a alone is
      insufficient for tumor initiation but it requires additional genetic
      alteration(s) such as Pten deletion to drive tumorigenesis. 

PMID- 24899689
TI  - Cardiac fibroblast glycogen synthase kinase-3beta regulates ventricular
      remodeling and dysfunction in ischemic heart.
AB  - BACKGROUND: Myocardial infarction-induced remodeling includes chamber dilatation,
      contractile dysfunction, and fibrosis. Of these, fibrosis is the least
      understood. After myocardial infarction, activated cardiac fibroblasts deposit
      extracellular matrix. Current therapies to prevent fibrosis are inadequate, and
      new molecular targets are needed. METHODS AND RESULTS: Herein we report that
      glycogen synthase kinase-3beta (GSK-3beta) is phosphorylated (inhibited) in
      fibrotic tissues from ischemic human and mouse heart. Using 2 fibroblast-specific
      GSK-3beta knockout mouse models, we show that deletion of GSK-3beta in cardiac
      fibroblasts leads to fibrogenesis, left ventricular dysfunction, and excessive
      scarring in the ischemic heart. Deletion of GSK-3beta induces a profibrotic
      myofibroblast phenotype in isolated cardiac fibroblasts, in post-myocardial
      infarction hearts, and in mouse embryonic fibroblasts deleted for GSK-3beta.
      Mechanistically, GSK-3beta inhibits profibrotic transforming growth factor
      beta1/SMAD-3 signaling via interactions with SMAD-3. Moreover, deletion of GSK
      3beta resulted in the significant increase of SMAD-3 transcriptional activity.
      This pathway is central to the pathology because a small-molecule inhibitor of
      SMAD-3 largely prevented fibrosis and limited left ventricular remodeling.
      CONCLUSIONS: These studies support targeting GSK-3beta in myocardial fibrotic
      disorders and establish critical roles of cardiac fibroblasts in remodeling and
      ventricular dysfunction.

PMID- 24899690
TI  - Inhibition of phosphodiesterase 2 augments cGMP and cAMP signaling to ameliorate
      pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a life-threatening disorder
      characterized by increased pulmonary artery pressure, remodeling of the pulmonary
      vasculature, and right ventricular failure. Loss of endothelium-derived nitric
      oxide (NO) and prostacyclin contributes to PH pathogenesis, and current therapies
      are targeted to restore these pathways. Phosphodiesterases (PDEs) are a family of
      enzymes that break down cGMP and cAMP, which underpin the bioactivity of NO and
      prostacyclin. PDE5 inhibitors (eg, sildenafil) are licensed for PH, but a role
      for PDE2 in lung physiology and disease has yet to be established. Herein, we
      investigated whether PDE2 inhibition modulates pulmonary cyclic nucleotide
      signaling and ameliorates experimental PH. METHODS AND RESULTS: The selective
      PDE2 inhibitor BAY 60-7550 augmented atrial natriuretic peptide- and treprostinil
      evoked pulmonary vascular relaxation in isolated arteries from chronically
      hypoxic rats. BAY 60-7550 prevented the onset of both hypoxia- and bleomycin
      induced PH and produced a significantly greater reduction in disease severity
      when given in combination with a neutral endopeptidase inhibitor (enhances
      endogenous natriuretic peptides), trepostinil, inorganic nitrate (NO donor), or a
      PDE5 inhibitor. Proliferation of pulmonary artery smooth muscle cells from
      patients with pulmonary arterial hypertension was reduced by BAY 60-7550, an
      effect further enhanced in the presence of atrial natriuretic peptide, NO, and
      treprostinil. CONCLUSIONS: PDE2 inhibition elicits pulmonary dilation, prevents
      pulmonary vascular remodeling, and reduces the right ventricular hypertrophy
      characteristic of PH. This favorable pharmacodynamic profile is dependent on
      natriuretic peptide bioactivity and is additive with prostacyclin analogues, PDE5
      inhibitor, and NO. PDE2 inhibition represents a viable, orally active therapy for
      PH.

PMID- 24899691
TI  - Next-generation sequencing of translocation renal cell carcinoma reveals novel
      RNA splicing partners and frequent mutations of chromatin-remodeling genes.
AB  - PURPOSE: MITF/TFE translocation renal cell carcinoma (TRCC) is a rare subtype of
      kidney cancer. Its incidence and the genome-wide characterization of its genetic
      origin have not been fully elucidated. EXPERIMENTAL DESIGN: We performed RNA and
      exome sequencing on an exploratory set of TRCC (n = 7), and validated our
      findings using The Cancer Genome Atlas (TCGA) clear-cell RCC (ccRCC) dataset (n =
      460). RESULTS: Using the TCGA dataset, we identified seven TRCC (1.5%) cases and
      determined their genomic profile. We discovered three novel partners of MITF/TFE
      (LUC7L3, KHSRP, and KHDRBS2) that are involved in RNA splicing. TRCC displayed a
      unique gene expression signature as compared with other RCC types, and showed
      activation of MITF, the transforming growth factor beta1 and the PI3K complex
      targets. Genes differentially spliced between TRCC and other RCC types were
      enriched for MITF and ID2 targets. Exome sequencing of TRCC revealed a distinct
      mutational spectrum as compared with ccRCC, with frequent mutations in chromatin
      remodeling genes (six of eight cases, three of which were from the TCGA). In two
      cases, we identified mutations in INO80D, an ATP-dependent chromatin-remodeling
      gene, previously shown to control the amplitude of the S phase. Knockdown of
      INO80D decreased cell proliferation in a novel cell line bearing LUC7L3-TFE3
      translocation. CONCLUSIONS: This genome-wide study defines the incidence of TRCC
      within a ccRCC-directed project and expands the genomic spectrum of TRCC by
      identifying novel MITF/TFE partners involved in RNA splicing and frequent
      mutations in chromatin-remodeling genes.

PMID- 24899692
TI  - Use of copy number deletion polymorphisms to assess DNA chimerism.
AB  - BACKGROUND: We describe a novel approach that harnesses the ubiquity of copy
      number deletion polymorphisms in human genomes to definitively detect and
      quantify chimeric DNA in clinical samples. Unlike other molecular approaches to
      chimerism analysis, the copy number deletion (CND) method targets genomic loci
      (>50 base pairs in length) that are wholly absent from wild-type (i.e., self)
      background DNA sequences in a sex-independent manner. METHODS: Bespoke
      quantitative PCR (qPCR) CND assays were developed and validated using a series of
      DNA standards and chimeric plasma DNA samples collected from 2 allogeneic kidney
      transplant recipients and 12 pregnant women. Assay performance and
      informativeness were assessed using appropriate statistical methods. RESULTS: The
      CND qPCR assays showed high sensitivity, precision, and reliability for linear
      quantification of DNA chimerism down to 16 genomic equivalents (i.e., 106 pg).
      Fetal fraction (%) in 12 singleton male pregnancies was calculated using the CND
      qPCR approach, which showed closer agreement with single-nucleotide polymorphism
      based massively parallel sequencing than the SRY (sex determining region Y) (Y
      chromosome) qPCR assay. The latter consistently underestimated the fetal fraction
      relative to the other methods. We also were able to measure biological changes in
      plasma nonself DNA concentrations in 2 renal transplant recipients. CONCLUSIONS:
      The CND qPCR technique is suitable for measurement of chimerism for monitoring of
      rejection in allogeneic organ transplantation and quantification of the cell-free
      fetal DNA fraction in maternal plasma samples used for noninvasive prenatal
      genetic testing.

PMID- 24899693
TI  - Immunoextraction-tandem mass spectrometry method for measuring intact human
      chorionic gonadotropin, free beta-subunit, and beta-subunit core fragment in
      urine.
AB  - BACKGROUND: Human chorionic gonadotropin (hCG) stimulates testosterone production
      by the testicles. Because of the potential for abuse, hCG is banned (males only)
      in most sports and has been placed on the World Anti-Doping Agency list of
      prohibited substances. Intact hCG, free beta-subunit (hCGbeta), and beta-subunit
      core fragment (hCGbetacf) are the major variants or isoforms in urine.
      Immunoassays are used by antidoping laboratories to measure urinary hCG. Cross
      reactivity with isoforms differs among immunoassays, resulting in widely varying
      results. We developed a sequential immunoextraction method with LC-MS/MS
      detection for quantification of intact hCG, hCGbeta, and hCGbetacf in urine.
      METHODS: hCG isoforms were immunoextracted with antibody-conjugated magnetic
      beads and digested with trypsin, and hCGbeta and hCGbetacf unique peptides were
      quantified by LC-MS/MS with the corresponding heavy peptides as internal
      standard. hCG isoform concentrations were determined in urine after
      administration of hCG, and the intact hCG results were compared to immunoassay
      results. RESULTS: The method was linear to 20 IU/L. Total imprecision was 6.6%
      13.7% (CV), recovery ranged from 91% to 109%, and the limit of quantification was
      0.2 IU/L. Intact hCG predominated in the urine after administration of 2 hCG
      formulations. The window of detection ranged from 6 to 9 days. Mean immunoassay
      results were 12.4-15.5 IU/L higher than LC-MS/MS results. CONCLUSIONS: The
      performance characteristics of the method are acceptable for measuring hCG
      isoforms, and the method can quantify intact hCG and hCGbeta separately. The
      limit of quantification will allow LC-MS/MS hCG reference intervals to be
      established in nondoping male athletes for improved doping control.

PMID- 24899694
TI  - Regulation of Staphylococcal Superantigen-Like Gene, ssl8, Expression in
      Staphylococcus aureus strain, RN6390.
AB  - Staphylococcal superantigen-like (SSL) proteins, which are encoded by a cluster
      of eleven ssl genes, contribute to the Staphylococcus aureus virulence. Recently
      we reported ssl8 expression profiles in seven clinically important strains-MW2,
      USA300FPR3757, MSSA476, Newman, RN6390, Mu50, and N315-and showed the
      differential expression of ssl8 in Newman, RN6390, and USA300FPR3757 strains,
      despite harboring identical allelic forms of ssl8, suggesting the roles for
      different regulatory elements for this gene in different S. aureus strains. In
      this communication, using RN6390, a common laboratory S. aureus strain and its
      isogenic knockout mutant strains of agr, sae, sarA, sigB, rot, and the agr-/sigB
      (-) double mutant, we showed that SarA and Rot are inducer and repressor,
      respectively, for ssl8 expression in RN6390. This is in contrast to the Newman
      strain, where ssl8 is positively regulated by Sae but negatively by Agr,
      indicating the variable expression of ssl8 in clinical strains is more likely due
      to strain-specific regulatory elements.

PMID- 24899696
TI  - Adenosine sheds light on the relationship between alcohol and sleep.

PMID- 24899695
TI  - Reinitiating warfarin: relationships between dose and selected patient, clinical
      and hospital measures.
AB  - BACKGROUND: Warfarin is an oral anticoagulant used in the long-term
      treatment/prevention of venothromboembolic disease. Patients undergoing elective
      surgical and non-surgical procedures may require temporary warfarin
      discontinuation followed by reinitiation after their procedure. Because little
      information is available regarding best methods for warfarin reinitiation, we
      investigated current practices to inform management decisions. METHODS: Subjects
      were required to have a known and stable warfarin dose prior to discontinuation,
      which was operationalized by requiring, within 7-days prior to discontinuation,
      that they have at least one INR in therapeutic range (2.0-3.5), no INR(s) out of
      range, and no more than a 15% change in warfarin dose. Stable dose prior to
      discontinuation was defined as the average daily dose received in the 7 days
      immediately prior to discontinuation. Reinitiation dose was defined as the
      average daily dose received in the first 3 days after warfarin was restarted.
      Subjects were divided into three groups based on whether they received
      approximately the same, a higher, or a lower dose at reinitiation and were also
      grouped by calendar time into three distinct periods that reflected differing
      levels of availability of electronic and patient care data that may impact
      reinitiation dose decisions. These groupings facilitated analyses and
      descriptions of trends in reinitiation dosing and supported other analyses,
      including tests for association between dose group and selected subject
      demographic, clinical, medication and hospitalization measures. All study data
      were abstracted from Marshfield Clinic electronic patient care and administrative
      databases and electronic patient care databases from Ministry St. Joseph's
      Hospital (Marshfield, WI). RESULTS: We identified 205 subjects with warfarin
      temporarily discontinued between 1994 and 2012: 99 subjects in same dose group,
      32 subjects in the low group, and 74 subjects in the high group. Because
      relatively wide differences were observed in the proportion of same dose subjects
      during more recent years (2007-2012) compared to earlier years (54% vs 35%), we
      focused our analyses on this recent period, which included 140 subjects. Review
      of physician notes and other documents yielded virtually no information about
      reasons for reinitiation dose decisions. In addition, tests for association
      between reinitiation dose group and subject demographic, clinical, medication and
      hospital measures were uniformly uninformative. CONCLUSIONS: We observed varied
      dosing strategies for reinitiating patients on warfarin and, in more recent
      years, an apparent trend toward reinitiating patients on the same dose. However
      we could not associate dosing strategy with specific patient demographic,
      clinical, medication or hospital factors. Many factors influence whether a
      physician reinitiates a patient at a different dose than his/her prior stable
      warfarin dose. However, in the absence of clinical indications for modification,
      we believe patients with a previously established effective dose should be
      reinitiated at that same dose following temporary warfarin discontinuation.

PMID- 24899697
TI  - Oscillatory brain state predicts variability in working memory.
AB  - Our capacity to remember and manipulate objects in working memory (WM) is
      severely limited. However, this capacity limitation is unlikely to be fixed
      because behavioral models indicate variability from trial to trial. We
      investigated whether fluctuations in neural excitability at stimulus encoding, as
      indexed by low-frequency oscillations (in the alpha band, 8-14 Hz), contribute to
      this variability. Specifically, we hypothesized that the spontaneous state of
      alpha band activity would correlate with trial-by-trial fluctuations in visual
      WM. Electroencephalography recorded from human observers during a visual WM task
      revealed that the prestimulus desynchronization of alpha oscillations predicts
      the accuracy of memory recall on a trial-by-trial basis. A model-based analysis
      indicated that this effect arises from a modulation in the precision of memorized
      items, but not the likelihood of remembering them (the recall rate). The phase of
      posterior alpha oscillations preceding the memorized item also predicted memory
      accuracy. Based on correlations between prestimulus alpha levels and stimulus
      related visual evoked responses, we speculate that the prestimulus state of the
      visual system prefigures a cascade of state-dependent processes, ultimately
      affecting WM-guided behavior. Overall, our results indicate that spontaneous
      changes in cortical excitability can have profound consequences for higher visual
      cognition. 

PMID- 24899698
TI  - Brain substrates of recovery from misleading influence.
AB  - Humans are strongly influenced by their environment, a dependence that can lead
      to errors in judgment. Although a rich literature describes how people are
      influenced by others, little is known regarding the factors that predict
      subsequent rectification of misleading influence. Using a mediation model in
      combination with brain imaging, we propose a model for the correction of
      misinformation. Specifically, our data suggest that amygdala modulation of
      hippocampal mnemonic representations, during the time of misleading social
      influence, is associated with reduced subsequent anterior-lateral prefrontal
      cortex activity that reflects correction. These findings illuminate the process
      by which erroneous beliefs are, or fail to be, rectified and highlight how past
      influence constrains subsequent correction. 

PMID- 24899700
TI  - Neuronal nitric oxide synthase-dependent S-nitrosylation of gephyrin regulates
      gephyrin clustering at GABAergic synapses.
AB  - Gephyrin, the principal scaffolding protein at inhibitory synapses, is essential
      for postsynaptic clustering of glycine and GABA type A receptors (GABA(A)Rs).
      Gephyrin cluster formation, which determines the strength of GABAergic
      transmission, is modulated by interaction with signaling proteins and post
      translational modifications. Here, we show that gephyrin was found to be
      associated with neuronal nitric oxide synthase (nNOS), the major source of the
      ubiquitous and important signaling molecule NO in brain. Furthermore, we
      identified that gephyrin is S-nitrosylated in vivo. Overexpression of nNOS
      decreased the size of postsynaptic gephyrin clusters in primary hippocampal
      neurons. Conversely, inhibition of nNOS resulted in a loss of S-nitrosylation of
      gephyrin and the formation of larger gephyrin clusters at synaptic sites,
      ultimately increasing the number of cell surface expressed synaptic GABA(A)Rs. In
      conclusion, S-nitrosylation of gephyrin is important for homeostatic assembly and
      plasticity of GABAergic synapses.

PMID- 24899699
TI  - Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced
      by MDMA (Ecstasy) under conditions that mimic human drug use.
AB  - MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave"
      parties, yet the data on potential health hazards of its abuse remain
      controversial. Here, we examined the effect of MDMA on temperature homeostasis in
      male rats under standard laboratory conditions and under conditions that simulate
      drug use in humans. We chronically implanted thermocouple microsensors in the
      nucleus accumbens (a brain reward area), temporal muscle, and facial skin to
      measure temperature continuously from freely moving rats. While focusing on brain
      hyperthermia, temperature monitoring from the two peripheral locations allowed us
      to evaluate the physiological mechanisms (i.e., intracerebral heat production and
      heat loss via skin surfaces) that underlie MDMA-induced brain temperature
      responses. Our data confirm previous reports on high individual variability and
      relatively weak brain hyperthermic effects of MDMA under standard control
      conditions (quiet rest, 22-23 degrees C), but demonstrate dramatic enhancements
      of drug-induced brain hyperthermia during social interaction (exposure to male
      conspecific) and in warm environments (29 degrees C). Importantly, we identified
      peripheral vasoconstriction as a critical mechanism underlying the activity- and
      state-dependent potentiation of MDMA-induced brain hyperthermia. Through this
      mechanism, which prevents proper heat dissipation to the external environment,
      MDMA at a moderate nontoxic dose (9 mg/kg or ~1/5 of LD50 in rats) can cause
      fatal hyperthermia under environmental conditions commonly encountered by humans.
      Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet
      conditions can become highly dangerous under conditions that mimic recreational
      use of MDMA at rave parties or other hot, crowded venues.

PMID- 24899702
TI  - Neuronal correlates of visual working memory in the corvid endbrain.
AB  - The concept of working memory is key to cognitive functioning. Working memory
      encompasses the capacity to retain immediately past information, to process this
      information, and to use it to guide goal-directed behavior. Corvid songbirds are
      renowned for their high-level cognitive capabilities, but where and how visual
      information is temporarily retained by neurons in the avian brain in a
      behaviorally relevant way remains poorly understood. We trained four carrion
      crows (Corvus corone) on versions of a delayed match-to-sample task that required
      the crows to remember a visual stimulus for later comparison. While the crows
      performed the task, we recorded the activity of single neurons in the nidopallium
      caudolaterale (NCL), a pallial association area of the avian endbrain. We show
      that many NCL neurons encode information about visual stimuli and temporarily
      maintain this information after the stimulus disappeared by sustained delay
      activity. Selective delay activity allows the birds to hold relevant information
      in memory and correlates with discrimination behavior. This suggests that
      sustained activity of NCL neurons is a neuronal correlate of visual working
      memory in the corvid brain and serves to bridge temporal gaps, thereby offering a
      workspace for processing immediately past visual information. 

PMID- 24899701
TI  - Mouse visual neocortex supports multiple stereotyped patterns of microcircuit
      activity.
AB  - Spiking correlations between neocortical neurons provide insight into the
      underlying synaptic connectivity that defines cortical microcircuitry. Here,
      using two-photon calcium fluorescence imaging, we observed the simultaneous
      dynamics of hundreds of neurons in slices of mouse primary visual cortex (V1).
      Consistent with a balance of excitation and inhibition, V1 dynamics were
      characterized by a linear scaling between firing rate and circuit size. Using
      lagged firing correlations between neurons, we generated functional wiring
      diagrams to evaluate the topological features of V1 microcircuitry. We found that
      circuit connectivity exhibited both cyclic graph motifs, indicating recurrent
      wiring, and acyclic graph motifs, indicating feedforward wiring. After overlaying
      the functional wiring diagrams onto the imaged field of view, we found properties
      consistent with Rentian scaling: wiring diagrams were topologically efficient
      because they minimized wiring with a modular architecture. Within single imaged
      fields of view, V1 contained multiple discrete circuits that were overlapping and
      highly interdigitated but were still distinct from one another. The majority of
      neurons that were shared between circuits displayed peri-event spiking activity
      whose timing was specific to the active circuit, whereas spike times for a
      smaller percentage of neurons were invariant to circuit identity. These data
      provide evidence that V1 microcircuitry exhibits balanced dynamics, is
      efficiently arranged in anatomical space, and is capable of supporting a
      diversity of multineuron spike firing patterns from overlapping sets of neurons. 

PMID- 24899703
TI  - Cortical interneurons require Jnk1 to enter and navigate the developing cerebral
      cortex.
AB  - Proper assembly of cortical circuitry relies on the correct migration of cortical
      interneurons from their place of birth in the ganglionic eminences to their place
      of terminal differentiation in the cerebral cortex. Although molecular mechanisms
      mediating cortical interneuron migration have been well studied, intracellular
      signals directing their migration are largely unknown. Here we illustrate a novel
      and essential role for c-Jun N-terminal kinase (JNK) signaling in guiding the
      pioneering population of cortical interneurons into the mouse cerebral cortex.
      Migrating cortical interneurons express Jnk proteins at the entrance to the
      cortical rudiment and have enriched expression of Jnk1 relative to
      noninterneuronal cortical cells. Pharmacological blockade of JNK signaling in ex
      vivo slice cultures resulted in dose-dependent and highly specific disruption of
      interneuron migration into the nascent cortex. Time-lapse imaging revealed that
      JNK-inhibited cortical interneurons advanced slowly and assumed aberrant
      migratory trajectories while traversing the cortical entry zone. In vivo analyses
      of JNK-deficient embryos supported our ex vivo pharmacological data. Deficits in
      interneuron migration were observed in Jnk1 but not Jnk2 single nulls, and those
      migratory deficits were further exacerbated when homozygous loss of Jnk1 was
      combined with heterozygous reduction of Jnk2. Finally, genetic ablation of Jnk1
      and Jnk2 from cortical interneurons significantly perturbed migration in vivo,
      but not in vitro, suggesting JNK activity functions to direct their guidance
      rather than enhance their motility. These data suggest JNK signaling,
      predominantly mediated by interneuron expressed Jnk1, is required for guiding
      migration of cortical interneurons into and within the developing cerebral
      cortex. 

PMID- 24899705
TI  - Impulse control disorders in Parkinson's disease are associated with dysfunction
      in stimulus valuation but not action valuation.
AB  - A substantial subset of Parkinson's disease (PD) patients suffers from impulse
      control disorders (ICDs), which are side effects of dopaminergic medication.
      Dopamine plays a key role in reinforcement learning processes. One class of
      reinforcement learning models, known as the actor-critic model, suggests that two
      components are involved in these reinforcement learning processes: a critic,
      which estimates values of stimuli and calculates prediction errors, and an actor,
      which estimates values of potential actions. To understand the information
      processing mechanism underlying impulsive behavior, we investigated stimulus and
      action value learning from reward and punishment in four groups of participants:
      on-medication PD patients with ICD, on-medication PD patients without ICD, off
      medication PD patients without ICD, and healthy controls. Analysis of responses
      suggested that participants used an actor-critic learning strategy and computed
      prediction errors based on stimulus values rather than action values.
      Quantitative model fits also revealed that an actor-critic model of the basal
      ganglia with different learning rates for positive and negative prediction errors
      best matched the choice data. Moreover, whereas ICDs were associated with model
      parameters related to stimulus valuation (critic), PD was associated with
      parameters related to action valuation (actor). Specifically, PD patients with
      ICD exhibited lower learning from negative prediction errors in the critic,
      resulting in an underestimation of adverse consequences associated with stimuli.
      These findings offer a specific neurocomputational account of the nature of
      compulsive behaviors induced by dopaminergic drugs. 

PMID- 24899706
TI  - Lasting impact of regret and gratification on resting brain activity and its
      relation to depressive traits.
AB  - Obtaining lower gains than rejected alternatives during decision making evokes
      feelings of regret, whereas higher gains elicit gratification. Although decision
      related emotions produce lingering effects on mental state, neuroscience research
      has generally focused on transient brain responses to positive or negative
      events, but ignored more sustained consequences of emotional episodes on
      subsequent brain states. We investigated how spontaneous brain activity and
      functional connectivity at rest are modulated by postdecision regret and
      gratification in 18 healthy human subjects using a gambling task in fMRI.
      Differences between obtained and unobtained outcomes were manipulated
      parametrically to evoke different levels of regret or gratification. We
      investigated how individual personality traits related to depression and
      rumination affected these responses. Medial and ventral prefrontal areas
      differentially responded to favorable and unfavorable outcomes during the
      gambling period. More critically, during subsequent rest, rostral anterior and
      posterior cingulate cortex, ventral striatum, and insula showed parametric
      response to the gratification level of preceding outcomes. Functional coupling of
      posterior cingulate with striatum and amygdala was also enhanced during rest
      after high gratification. Regret produced distinct changes in connectivity of
      subgenual cingulate with orbitofrontal cortex and thalamus. Interestingly,
      individual differences in depressive traits and ruminations correlated with
      activity of the striatum after gratification and orbitofrontal cortex after
      regret, respectively. By revealing lingering effects of decision-related emotions
      on key nodes of resting state networks, our findings illuminate how such emotions
      may influence self-reflective processing and subsequent behavioral adjustment,
      but also highlight the malleability of resting networks in emotional contexts. 

PMID- 24899704
TI  - FUS is phosphorylated by DNA-PK and accumulates in the cytoplasm after DNA
      damage.
AB  - Abnormal cytoplasmic accumulation of Fused in Sarcoma (FUS) in neurons defines
      subtypes of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar
      degeneration (FTLD). FUS is a member of the FET protein family that includes
      Ewing's sarcoma (EWS) and TATA-binding protein-associated factor 2N (TAF15). FET
      proteins are predominantly localized to the nucleus, where they bind RNA and DNA
      to modulate transcription, mRNA splicing, and DNA repair. In ALS cases with FUS
      inclusions (ALS-FUS), mutations in the FUS gene cause disease, whereas FTLD cases
      with FUS inclusions (FTLD-FUS) do not harbor FUS mutations. Notably, in FTLD-FUS,
      all FET proteins accumulate with their nuclear import receptor Transportin 1
      (TRN1), in contrast ALS-FUS inclusions are exclusively positive for FUS. In the
      present study, we show that induction of DNA damage replicates several pathologic
      hallmarks of FTLD-FUS in immortalized human cells and primary human neurons and
      astrocytes. Treatment with the antibiotic calicheamicin gamma1, which causes DNA
      double-strand breaks, leads to the cytoplasmic accumulation of FUS, TAF15, EWS,
      and TRN1. Moreover, cytoplasmic translocation of FUS is mediated by
      phosphorylation of its N terminus by the DNA-dependent protein kinase. Finally,
      we observed elevated levels of phospho-H2AX in FTLD-FUS brains, indicating that
      DNA damage occurs in patients. Together, our data reveal a novel regulatory
      mechanism for FUS localization in cells and suggest that DNA damage may
      contribute to the accumulation of FET proteins observed in human FTLD-FUS cases,
      but not in ALS-FUS. 

PMID- 24899707
TI  - Pot1a prevents telomere dysfunction and ATM-dependent neuronal loss.
AB  - Genome stability is essential for neural development and the prevention of
      neurological disease. Here we determined how DNA damage signaling from
      dysfunctional telomeres affects neurogenesis. We found that telomere uncapping by
      Pot1a inactivation resulted in an Atm-dependent loss of cerebellar interneurons
      and granule neuron precursors in the mouse nervous system. The activation of Atm
      by Pot1a loss occurred in an Atr-dependent manner, revealing an Atr to Atm
      signaling axis in the nervous system after telomere dysfunction. In contrast to
      telomere lesions, Brca2 inactivation in neural progenitors also led to ablation
      of cerebellar interneurons, but this did not require Atm. These data reveal that
      neural cell loss after DNA damage selectively engages Atm signaling, highlighting
      how specific DNA lesions can dictate neuropathology arising in human
      neurodegenerative syndromes. 

PMID- 24899708
TI  - Genetically targeted binary labeling of retinal neurons.
AB  - A major stumbling block to understanding neural circuits is the extreme
      anatomical and functional diversity of interneurons. Subsets of interneurons can
      be targeted for manipulation using Cre mouse lines, but Cre expression is rarely
      confined to a single interneuron type. It is essential to have a strategy that
      further restricts labeling in Cre driver lines. We now describe an approach that
      combines Cre driver mice, recombinant adeno-associated virus, and rabies virus to
      produce sparse but binary labeling of select interneurons--frequently only a
      single cell in a large region. We used this approach to characterize the retinal
      amacrine and ganglion cell types in five GABAergic Cre mouse (Mus musculus)
      lines, and identified two new amacrine cell types: an asymmetric medium-field
      type and a wide-field type. We also labeled several wide-field amacrine cell
      types that have been previously identified based on morphology but whose
      connectivity and function had not been systematically studied due to lack of
      genetic markers. All Cre-expressing amacrine cells labeled with an antibody to
      GABA. Cre-expressing RGCs lacked GABA labeling and included classically defined
      as well as recently identified types. In addition to the retina, our technique
      leads to sparse labeling of neurons in the cortex, lateral geniculate nucleus,
      and superior colliculus, and can be used to express optogenetic tools such as
      channelrhodopsin and protein sensors such as GCaMP. The Cre drivers identified in
      this study provide genetic access to otherwise hard to access cell types for
      systematic analysis including anatomical characterization, physiological
      recording, optogenetic and/or chemical manipulation, and circuit mapping.

PMID- 24899709
TI  - Effects of resveratrol on memory performance, hippocampal functional
      connectivity, and glucose metabolism in healthy older adults.
AB  - Dietary habits such as caloric restriction or nutrients that mimic these effects
      may exert beneficial effects on brain aging. The plant-derived polyphenol
      resveratrol has been shown to increase memory performance in primates; however,
      interventional studies in older humans are lacking. Here, we tested whether
      supplementation of resveratrol would enhance memory performance in older adults
      and addressed potential mechanisms underlying this effect. Twenty-three healthy
      overweight older individuals that successfully completed 26 weeks of resveratrol
      intake (200 mg/d) were pairwise matched to 23 participants that received placebo
      (total n = 46, 18 females, 50-75 years). Before and after the
      intervention/control period, subjects underwent memory tasks and neuroimaging to
      assess volume, microstructure, and functional connectivity (FC) of the
      hippocampus, a key region implicated in memory functions. In addition,
      anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors,
      and vascular parameters were assayed. We observed a significant effect of
      resveratrol on retention of words over 30 min compared with placebo (p = 0.038).
      In addition, resveratrol led to significant increases in hippocampal FC,
      decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin
      compared with placebo (all p < 0.05). Increases in FC between the left posterior
      hippocampus and the medial prefrontal cortex correlated with increases in
      retention scores and with decreases in HbA1c (all p < 0.05). This study provides
      initial evidence that supplementary resveratrol improves memory performance in
      association with improved glucose metabolism and increased hippocampal FC in
      older adults. Our findings offer the basis for novel strategies to maintain brain
      health during aging. 

PMID- 24899710
TI  - Genetic modulation of soluble Abeta rescues cognitive and synaptic impairment in
      a mouse model of Alzheimer's disease.
AB  - An unresolved debate in Alzheimer's disease (AD) is whether amyloid plaques are
      pathogenic, causing overt physical disruption of neural circuits, or protective,
      sequestering soluble forms of amyloid-beta (Abeta) that initiate synaptic damage
      and cognitive decline. Few animal models of AD have been capable of isolating the
      relative contribution made by soluble and insoluble forms of Abeta to the
      behavioral symptoms and biochemical consequences of the disease. Here we use a
      controllable transgenic mouse model expressing a mutant form of amyloid precursor
      protein (APP) to distinguish the impact of soluble Abeta from that of deposited
      amyloid on cognitive function and synaptic structure. Rapid inhibition of
      transgenic APP modulated the production of Abeta without affecting pre-existing
      amyloid deposits and restored cognitive performance to the level of healthy
      controls in Morris water maze, radial arm water maze, and fear conditioning.
      Selective reduction of Abeta with a gamma-secretase inhibitor provided similar
      improvement, suggesting that transgene suppression restored cognition, at least
      in part by lowering Abeta. Cognitive improvement coincided with reduced levels of
      synaptotoxic Abeta oligomers, greater synaptic density surrounding amyloid
      plaques, and increased expression of presynaptic and postsynaptic markers.
      Together these findings indicate that transient Abeta species underlie much of
      the cognitive and synaptic deficits observed in this model and demonstrate that
      significant functional and structural recovery can be attained without removing
      deposited amyloid. 

PMID- 24899711
TI  - How local excitation-inhibition ratio impacts the whole brain dynamics.
AB  - The spontaneous activity of the brain shows different features at different
      scales. On one hand, neuroimaging studies show that long-range correlations are
      highly structured in spatiotemporal patterns, known as resting-state networks, on
      the other hand, neurophysiological reports show that short-range correlations
      between neighboring neurons are low, despite a large amount of shared presynaptic
      inputs. Different dynamical mechanisms of local decorrelation have been proposed,
      among which is feedback inhibition. Here, we investigated the effect of locally
      regulating the feedback inhibition on the global dynamics of a large-scale brain
      model, in which the long-range connections are given by diffusion imaging data of
      human subjects. We used simulations and analytical methods to show that locally
      constraining the feedback inhibition to compensate for the excess of long-range
      excitatory connectivity, to preserve the asynchronous state, crucially changes
      the characteristics of the emergent resting and evoked activity. First, it
      significantly improves the model's prediction of the empirical human functional
      connectivity. Second, relaxing this constraint leads to an unrealistic network
      evoked activity, with systematic coactivation of cortical areas which are
      components of the default-mode network, whereas regulation of feedback inhibition
      prevents this. Finally, information theoretic analysis shows that regulation of
      the local feedback inhibition increases both the entropy and the Fisher
      information of the network evoked responses. Hence, it enhances the information
      capacity and the discrimination accuracy of the global network. In conclusion,
      the local excitation-inhibition ratio impacts the structure of the spontaneous
      activity and the information transmission at the large-scale brain level. 

PMID- 24899713
TI  - Identification of optimal structural connectivity using functional connectivity
      and neural modeling.
AB  - The complex network dynamics that arise from the interaction of the brain's
      structural and functional architectures give rise to mental function. Theoretical
      models demonstrate that the structure-function relation is maximal when the
      global network dynamics operate at a critical point of state transition. In the
      present work, we used a dynamic mean-field neural model to fit empirical
      structural connectivity (SC) and functional connectivity (FC) data acquired in
      humans and macaques and developed a new iterative-fitting algorithm to optimize
      the SC matrix based on the FC matrix. A dramatic improvement of the fitting of
      the matrices was obtained with the addition of a small number of anatomical
      links, particularly cross-hemispheric connections, and reweighting of existing
      connections. We suggest that the notion of a critical working point, where the
      structure-function interplay is maximal, may provide a new way to link behavior
      and cognition, and a new perspective to understand recovery of function in
      clinical conditions. 

PMID- 24899712
TI  - BDNF signaling in the VTA links the drug-dependent state to drug withdrawal
      aversions.
AB  - Drug administration to avoid unpleasant drug withdrawal symptoms has been
      hypothesized to be a crucial factor that leads to compulsive drug-taking
      behavior. However, the neural relationship between the aversive motivational
      state produced by drug withdrawal and the development of the drug-dependent state
      still remains elusive. It has been observed that chronic exposure to drugs of
      abuse increases brain-derived neurotrophic factor (BDNF) levels in ventral
      tegmental area (VTA) neurons. In particular, BDNF expression is dramatically
      increased during drug withdrawal, which would suggest a direct connection between
      the aversive state of withdrawal and BDNF-induced neuronal plasticity. Using
      lentivirus-mediated gene transfer to locally knock down the expression of the
      BDNF receptor tropomyosin-receptor-kinase type B in rats and mice, we observed
      that chronic opiate administration activates BDNF-related neuronal plasticity in
      the VTA that is necessary for both the establishment of an opiate-dependent state
      and aversive withdrawal motivation. Our findings highlight the importance of a
      bivalent, plastic mechanism that drives the negative reinforcement underlying
      addiction. 

PMID- 24899714
TI  - TGFbeta signaling regulates the timing of CNS myelination by modulating
      oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1.
AB  - Research on myelination has focused on identifying molecules capable of inducing
      oligodendrocyte (OL) differentiation in an effort to develop strategies that
      promote functional myelin regeneration in demyelinating disorders. Here, we show
      that transforming growth factor beta (TGFbeta) signaling is crucial for allowing
      oligodendrocyte progenitor (OP) cell cycle withdrawal, and therefore, for
      oligodendrogenesis and postnatal CNS myelination. Enhanced oligodendrogenesis and
      subcortical white matter (SCWM) myelination was detected after TGFbeta gain of
      function, while TGFbeta receptor II (TGFbeta-RII) deletion in OPs prevents their
      development into mature myelinating OLs, leading to SCWM hypomyelination in mice.
      TGFbeta signaling modulates OP cell cycle withdrawal and differentiation through
      the transcriptional modulation of c-myc and p21 gene expression, mediated by the
      interaction of SMAD3/4 with Sp1 and FoxO1 transcription factors. Our study is the
      first to demonstrate an autonomous and crucial role of TGFbeta signaling in OL
      development and CNS myelination, and may provide new avenues in the treatment of
      demyelinating diseases. 

PMID- 24899716
TI  - Novelty enhances visual salience independently of reward in the parietal lobe.
AB  - Novelty modulates sensory and reward processes, but it remains unknown how these
      effects interact, i.e., how the visual effects of novelty are related to its
      motivational effects. A widespread hypothesis, based on findings that novelty
      activates reward-related structures, is that all the effects of novelty are
      explained in terms of reward. According to this idea, a novel stimulus is by
      default assigned high reward value and hence high salience, but this salience
      rapidly decreases if the stimulus signals a negative outcome. Here we show that,
      contrary to this idea, novelty affects visual salience in the monkey lateral
      intraparietal area (LIP) in ways that are independent of expected reward. Monkeys
      viewed peripheral visual cues that were novel or familiar (received few or many
      exposures) and predicted whether the trial will have a positive or a negative
      outcome--i.e., end in a reward or a lack of reward. We used a saccade-based assay
      to detect whether the cues automatically attracted or repelled attention from
      their visual field location. We show that salience--measured in saccades and LIP
      responses--was enhanced by both novelty and positive reward associations, but
      these factors were dissociable and habituated on different timescales. The
      monkeys rapidly recognized that a novel stimulus signaled a negative outcome (and
      withheld anticipatory licking within the first few presentations), but the
      salience of that stimulus remained high for multiple subsequent presentations.
      Therefore, novelty can provide an intrinsic bonus for attention that extends
      beyond the first presentation and is independent of physical rewards.

PMID- 24899717
TI  - Presynaptic calcium channel inhibition underlies CB1 cannabinoid receptor
      mediated suppression of GABA release.
AB  - CB1 cannabinoid receptors (CB1) are located at axon terminals and effectively
      control synaptic communication and thereby circuit operation widespread in the
      CNS. Although it is partially uncovered how CB1 activation leads to the reduction
      of synaptic excitation, the mechanisms of the decrease of GABA release upon
      activation of these cannabinoid receptors remain elusive. To determine the
      mechanisms underlying the suppression of synaptic transmission by CB1 at
      GABAergic synapses, we recorded unitary IPSCs (uIPSCs) at cholecystokinin
      expressing interneuron-pyramidal cell connections and imaged presynaptic [Ca(2+)]
      transients in mouse hippocampal slices. Our results reveal a power function with
      an exponent of 2.2 between the amplitude of uIPSCs and intrabouton [Ca(2+)].
      Altering CB1 function by either increasing endocannabinoid production or removing
      its tonic activity allowed us to demonstrate that CB1 controls GABA release by
      inhibiting Ca(2+) entry into presynaptic axon terminals via N-type (Cav2.2)
      Ca(2+) channels. These results provide evidence for modulation of intrabouton
      Ca(2+) influx into GABAergic axon terminals by CB1, leading to the effective
      suppression of synaptic inhibition. 

PMID- 24899715
TI  - Too little and too much: hypoactivation and disinhibition of medial prefrontal
      cortex cause attentional deficits.
AB  - Attentional deficits are core symptoms of schizophrenia, contributing strongly to
      disability. Prefrontal dysfunction has emerged as a candidate mechanism, with
      clinical evidence for prefrontal hypoactivation and disinhibition (reduced
      GABAergic inhibition), possibly reflecting different patient subpopulations.
      Here, we tested in rats whether imbalanced prefrontal neural activity impairs
      attention. To induce prefrontal hypoactivation or disinhibition, we microinfused
      the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or
      antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the
      medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT)
      test, we showed that both muscimol and picrotoxin impaired attention (reduced
      accuracy, increased omissions). Muscimol also impaired response control
      (increased premature responses). In addition, muscimol dose dependently reduced
      open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor
      hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected.
      Therefore, infusion effects on the 5CSRT test can be dissociated from
      sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we
      showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased
      firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting
      and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly
      enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and
      disinhibition both cause attentional deficits. Considering the
      electrophysiological findings, this suggests that attention requires
      appropriately tuned prefrontal activity. Apart from attentional deficits,
      prefrontal disinhibition caused additional neurobehavioral changes that may be
      relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting
      and locomotor hyperactivity, which have been linked to psychosis-related dopamine
      hyperfunction. 

PMID- 24899718
TI  - Frontal-medial temporal interactions mediate transitions among representational
      states in short-term memory.
AB  - Short-term memory (STM), the brief maintenance of information in the absence of
      external stimulation, is central to higher-level cognition. Behavioral and neural
      data indicate that information maintained in STM can be represented in
      qualitatively distinct states. These states include a single chunk held in the
      focus of attention available for immediate processing (the "focus"), a capacity
      limited set of additional actively maintained items that the focus can access
      (the "active state"), and passively maintained items (the "passive state").
      Little is known about how information is shifted among these states. Here, we
      used fMRI in humans to examine the neural correlates of shifting information
      among representational states of STM. We used a paradigm that has demonstrated
      dissociable performance costs associated with shifting the focus among active
      items and switching sets of items between active and passive states. Behavioral
      results confirmed distinct behavioral costs associated with different
      representational states. Neural results indicated that the caudal superior
      frontal sulcus (cSFS), in the vicinity of the frontal eye fields, was associated
      with shifting the focus, consistent with the role of this region in internal and
      external attention. By contrast, the ventral premotor cortex (PMv) was associated
      with shifting between active and passive states. Increased cSFS-medial temporal
      lobe (MTL) connectivity was associated with shifting the focus, while cSFS-MTL
      connectivity was disrupted when the active state was changed. By contrast, PMv
      MTL connectivity increased when the active state was switched. These data
      indicate that dissociable frontal-MTL interactions mediate shifts of information
      among different representational states in STM. 

PMID- 24899719
TI  - Response normalization in the superficial layers of the superior colliculus as a
      possible mechanism for saccadic averaging.
AB  - How does the brain decide where to look? Neuronal networks within the superior
      colliculus (SC) encode locations of intended eye movements. When faced with
      multiple targets, the relative activities of neuronal populations compete for the
      selection of a saccade. However, the computational principles underlying saccadic
      choices remain poorly understood. We used voltage imaging of slices of rat SC to
      record circuit dynamics of population responses to single- and dual-site
      electrical stimulation to begin to reveal some of the principles of how
      populations of neurons interact. Stimulation of two distant sites simultaneously
      within the SC produced two distinct peaks of activity, whereas stimulation of two
      nearby sites simultaneously exhibited a single, merged peak centered between the
      two sites. The distances required to produce merged peaks of activity
      corresponded to target separations that evoked averaging saccades in humans
      performing a corresponding dual target task. The merged activity was well
      accounted for by a linear weighed summation and a divisive normalization of the
      responses evoked by the single-site stimulations. Interestingly, the merging of
      activity occurred within the superficial SC, suggesting a novel pathway for
      saccadic eye movement choice. 

PMID- 24899722
TI  - Briefly cuing memories leads to suppression of their neural representations.
AB  - Previous studies have linked partial memory activation with impaired subsequent
      memory retrieval (e.g., Detre et al., 2013) but have not provided an account of
      this phenomenon at the level of memory representations: How does partial
      activation change the neural pattern subsequently elicited when the memory is
      cued? To address this question, we conducted a functional magnetic resonance
      imaging (fMRI) experiment in which participants studied word-scene paired
      associates. Later, we weakly reactivated some memories by briefly presenting the
      cue word during a rapid serial visual presentation (RSVP) task; other memories
      were more strongly reactivated or not reactivated at all. We tested participants'
      memory for the paired associates before and after RSVP. Cues that were briefly
      presented during RSVP triggered reduced levels of scene activity on the post-RSVP
      memory test, relative to the other conditions. We used pattern similarity
      analysis to assess how representations changed as a function of the RSVP
      manipulation. For briefly cued pairs, we found that neural patterns elicited by
      the same cue on the pre- and post-RSVP tests (preA-postA; preB-postB) were less
      similar than neural patterns elicited by different cues (preA-postB; preB-postA).
      These similarity reductions were predicted by neural measures of memory
      activation during RSVP. Through simulation, we show that our pattern similarity
      results are consistent with a model in which partial memory activation triggers
      selective weakening of the strongest parts of the memory. 

PMID- 24899720
TI  - Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer's
      disease-like cognitive and pathological deficits by restoring hippocampal gene
      expression signature.
AB  - Elevated mammalian target of rapamycin (mTOR) signaling has been found in
      Alzheimer's disease (AD) patients and is linked to diabetes and aging, two known
      risk factors for AD. However, whether hyperactive mTOR plays a role in the
      cognitive deficits associated with AD remains elusive. Here, we genetically
      reduced mTOR signaling in the brains of Tg2576 mice, a widely used animal model
      of AD. We found that suppression of mTOR signaling reduced amyloid-beta deposits
      and rescued memory deficits. Mechanistically, the reduction in mTOR signaling led
      to an increase in autophagy induction and restored the hippocampal gene
      expression signature of the Tg2576 mice to wild-type levels. Our results
      implicate hyperactive mTOR signaling as a previous unidentified signaling pathway
      underlying gene-expression dysregulation and cognitive deficits in AD.
      Furthermore, hyperactive mTOR signaling may represent a molecular pathway by
      which aging contributes to the development of AD. 

PMID- 24899721
TI  - Activity-dependent regulation of dendritic complexity by semaphorin 3A through
      Farp1.
AB  - Dendritic arbors are complex neuronal structures that receive and process
      synaptic inputs. One mechanism regulating dendrite differentiation is
      Semaphorin/Plexin signaling, specifically through binding of soluble Sema3A to
      Neuropilin/PlexinA coreceptors. Here we show that the protein Farp1 [FERM, RhoGEF
      (ARHGEF), and pleckstrin domain protein 1], a Rac1 activator previously
      identified as a synaptogenic signaling protein, contributes to establishing
      dendrite tip number and total dendritic branch length in maturing rat neurons and
      is sufficient to promote dendrite complexity. Aiming to define its upstream
      partners, our results support that Farp1 interacts with the Neuropilin-1/PlexinA1
      complex and colocalizes with PlexinA1 along dendritic shafts. Functionally, Farp1
      is required by Sema3A to promote dendritic arborization of hippocampal neurons,
      and Sema3A regulates dendritic F-actin distribution via Farp1. Unexpectedly,
      Sema3A also requires neuronal activity to promote dendritic complexity,
      presumably because silencing neurons leads to a proteasome-dependent reduction of
      PlexinA1 in dendrites. These results provide new insights into how activity and
      soluble cues cooperate to refine dendritic morphology through intracellular
      signaling pathways. 

PMID- 24899723
TI  - Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor
      neurons and improves the phenotype of a transgenic mouse model of amyotrophic
      lateral sclerosis.
AB  - Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause
      amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent
      phenotype in transgenic rodents. We show that oral treatment with the therapeutic
      agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)]
      increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but
      paradoxically improved locomotor function and survival of the mice. To determine
      why the mice with increased levels of mutant SOD1 had an improved phenotype, we
      analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the
      spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with
      Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of
      fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm)
      confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to
      SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)
      treated SOD1G37R mice involved, at least in part, the ability of the compound to
      improve the Cu content of the mutant SOD1. This was supported by improved
      survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein
      CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did
      not decrease levels of misfolded SOD1. These outcomes indicate the metal content
      of SOD1 may be a greater determinant of the toxicity of the protein in mutant
      SOD1-associated forms of ALS than the mutations themselves. Improving the metal
      content of SOD1 therefore represents a valid therapeutic strategy for treating
      ALS caused by SOD1. 

PMID- 24899725
TI  - Regulation of the VHL/HIF-1 pathway by DJ-1.
AB  - DJ-1 (PARK7) is a gene linked to autosomal recessive Parkinson disease (PD). We
      showed previously that DJ-1 loss sensitizes neurons in models of PD and stroke.
      However, the biochemical mechanisms underlying this protective role are not
      completely clear. Here, we identify Von Hippel Lindau (VHL) protein as a critical
      DJ-1-interacting protein. We provide evidence that DJ-1 negatively regulates VHL
      ubiquitination activity of the alpha-subunit of hypoxia-inducible factor-1 (HIF
      1alpha) by inhibiting HIF-VHL interaction. Consistent with this observation, DJ-1
      deficiency leads to lowered HIF-1alpha levels in models of both hypoxia and
      oxidative stress, two stresses known to stabilize HIF-1alpha. We also demonstrate
      that HIF-1alpha accumulation rescues DJ-1-deficient neurons against 1-methyl-4
      phenylpyridinium-induced toxicity. Interestingly, lymphoblast cells extracted
      from DJ-1-related PD patients show impaired HIF-1alpha stabilization when
      compared with normal individuals, indicating that the DJ-1-VHL link may also be
      relevant to a human context. Together, our findings delineate a model by which DJ
      1 mediates neuronal survival by regulation of the VHL-HIF-1alpha pathway. 

PMID- 24899727
TI  - Clinical neurology: a changing role?

PMID- 24899724
TI  - The substantia nigra conveys target-dependent excitatory and inhibitory outputs
      from the basal ganglia to the thalamus.
AB  - The basal ganglia (BG), which influence cortical activity via the thalamus, play
      a major role in motor activity, learning and memory, sensory processing, and many
      aspects of behavior. The substantia nigra (SN) consists of GABAergic neurons of
      the pars reticulata that inhibit thalamic neurons and provide the primary output
      of the BG, and dopaminergic neurons of the pars compacta that modulate thalamic
      excitability. Little is known about the functional properties of the SN->thalamus
      synapses, and anatomical characterization has been controversial. Here we use a
      combination of anatomical, electrophysiological, genetic, and optogenetic
      approaches to re-examine these synaptic connections in mice. We find that neurons
      in the SN inhibit neurons in the ventroposterolateral nucleus of the thalamus via
      GABAergic synapses, excite neurons in the thalamic nucleus reticularis, and both
      excite and inhibit neurons within the posterior nucleus group. Glutamatergic SN
      neurons express the vesicular glutamate receptor transporter vGluT2 and receive
      inhibitory synapses from striatal neurons, and many also express tyrosine
      hydroxylase, a marker of dopaminergic neurons. Thus, in addition to providing
      inhibitory outputs, which is consistent with the canonical circuit, the SN
      provides glutamatergic outputs that differentially target thalamic nuclei. This
      suggests that an increase in the activity of glutamatergic neurons in the SN
      allows the BG to directly excite neurons in specific thalamic nuclei. Elucidating
      an excitatory connection between the BG and the thalamus provides new insights
      into how the BG regulate thalamic activity, and has important implications for
      understanding BG function in health and disease. 

PMID- 24899726
TI  - Successful remembering elicits event-specific activity patterns in lateral
      parietal cortex.
AB  - Remembering a past event involves reactivation of content-specific patterns of
      neural activity in high-level perceptual regions (e.g., ventral temporal cortex,
      VTC). In contrast, the subjective experience of vivid remembering is typically
      associated with increased activity in lateral parietal cortex (LPC)--"retrieval
      success effects" that are thought to generalize across content types. However,
      the functional significance of LPC activation during memory retrieval remains a
      subject of active debate. In particular, theories are divided with respect to
      whether LPC actively represents retrieved content or if LPC activity only scales
      with content reactivation elsewhere (e.g., VTC). Here, we report a human fMRI
      study of visual memory recall (faces vs scenes) in which complementary forms of
      multivoxel pattern analysis were used to test for and compare content
      reactivation within LPC and VTC. During recall of visual images, we observed
      robust reactivation of broad category information (face vs scene) in both VTC and
      LPC. Moreover, recall-related activity patterns in LPC, but not VTC,
      differentiated between individual events. Importantly, these content effects were
      particularly evident in areas of LPC (namely, angular gyrus) in which activity
      scaled with subjective reports of recall vividness. These findings provide
      striking evidence that LPC not only signals that memories have been successfully
      recalled, but actively represents what is being remembered.

PMID- 24899729
TI  - Deep grey matter involvement in multiple sclerosis: key player or bystander?

PMID- 24899728
TI  - Multiple sclerosis deep grey matter: the relation between demyelination,
      neurodegeneration, inflammation and iron.
AB  - In multiple sclerosis (MS), diffuse degenerative processes in the deep grey
      matter have been associated with clinical disabilities. We performed a systematic
      study in MS deep grey matter with a focus on the incidence and topographical
      distribution of lesions in relation to white matter and cortex in a total sample
      of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of
      inflammation, acute axonal injury, iron deposition and oxidative stress were
      performed. MS deep grey matter was affected by two different processes: the
      formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey
      matter demyelination was most prominent in the caudate nucleus and hypothalamus
      and could already be seen in early MS stages. Lesions developed on the background
      of inflammation. Deep grey matter inflammation was intermediate between low
      inflammatory cortical lesions and active white matter lesions. Demyelination and
      neurodegeneration were associated with oxidative injury. Iron was stored
      primarily within oligodendrocytes and myelin fibres and released upon
      demyelination. In addition to focal demyelinated plaques, the MS deep grey matter
      also showed diffuse and global neurodegeneration. This was reflected by a global
      reduction of neuronal density, the presence of acutely injured axons, and the
      accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and
      axons. Neurodegeneration was associated with T cell infiltration, expression of
      inducible nitric oxide synthase in microglia and profound accumulation of iron.
      Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey
      matter appeared to contribute to the neurological disabilities of MS patients. 

PMID- 24899731
TI  - Out of sight but not out of harm's way: Human disturbance reduces reproductive
      success of a cavity-nesting seabird.
AB  - While negative effects of human disturbance on animals living above the ground
      have been widely reported, few studies have considered effects on animals
      occupying cavities or burrows underground. It is generally assumed that, in the
      absence of direct visual contact, such species are less vulnerable to
      disturbance. Seabird colonies can support large populations of burrow- and cavity
      nesting species and attract increasing numbers of tourists. We investigated the
      potential effects of recreational disturbance on the reproductive behaviour of
      the European storm petrel Hydrobates pelagicus, a nocturnally-active cavity
      nesting seabird. Reproductive phenology and outcome of nests subject to high and
      low levels of visitor pressure were recorded in two consecutive years. Hatching
      success did not differ between disturbance levels, but overall nestling mortality
      was significantly higher in areas exposed to high visitor pressure. Although
      visitor numbers were consistent throughout the season, the magnitude and rate of
      a seasonal decline in productivity were significantly greater in nests subject to
      high disturbance. This study presents good evidence that, even when humans do not
      pose a direct mortality risk, animals may perceive them as a predation risk. This
      has implications for the conservation and management of a diverse range of burrow
      and cavity-dwelling animals. Despite this reduction in individual fitness,
      overall colony productivity was reduced by ?1.6% compared with that expected in
      the absence of visitors. While the colony-level consequences at the site in
      question may be considered minor, conservation managers must evaluate the trade
      off between potential costs and benefits of public access on a site- and species
      specific basis.

PMID- 24899732
TI  - The Big Wait.

PMID- 24899730
TI  - Divergent CSF tau alterations in two common tauopathies: Alzheimer's disease and
      progressive supranuclear palsy.
AB  - BACKGROUND: Elevated CSF tau is considered a biomarker of neuronal injury in
      newly developed Alzheimer's disease (AD) and mild cognitive impairment (MCI)
      criteria. However, previous studies have failed to detect alterations of tau
      species in other primary tauopathies. We assessed CSF tau protein abnormalities
      in AD, a tauopathy with prominent Abeta pathology, and progressive supranuclear
      palsy (PSP), a primary tauopathy characterised by deposition of four microtubule
      binding repeat (4R) tau with minimal Abeta pathology. METHODS: 26 normal control
      (NC), 37 AD, and 24 patients with PSP participated in the study. AD and PSP were
      matched for severity using the clinical dementia rating sum of boxes (CDR-sb)
      scores. The INNO BIA AlzBio3 multiplex immunoassay was used to measure CSF Abeta,
      total tau, and ptau181. Additional, novel ELISAs targeting different N-terminal
      and central tau epitopes were developed to examine CSF tau components and to
      investigate interactions between diagnostic group, demographics and genetic
      variables. RESULTS: PSP had lower CSF N-terminal and C-terminal tau
      concentrations than NC and AD measured with the novel tau ELISAs and the standard
      AlzBio3 tau and ptau assays. AD had higher total tau and ptau levels than NC and
      PSP. There was a gender by diagnosis interaction in AD and PSP for most tau
      species, with lower concentrations for male compared to female patients.
      CONCLUSIONS: CSF tau fragment concentrations are different in PSP compared with
      AD despite the presence of severe tau pathology and neuronal injury in both
      disorders. CSF tau concentration likely reflects multiple factors in addition to
      the degree of neuronal injury.

PMID- 24899733
TI  - The U.S. Diversity Visa Programme and the Transfer of Skills from Africa.
AB  - The Diversity Visa (DV) programme is designed to improve the multicultural
      composition of the U.S. "melting pot" beyond the traditional source countries in
      Europe. In pursuit of this objective, the basic eligibility requirement for
      participation in the programme is a high school diploma. Despite its salutary
      objective and design, the programme's implications for the African brain drain
      may not all be benign. The "tired, poor, huddled masses" from Africa are defined
      in more restrictive terms, and the obstacles they face are more economically and
      administratively onerous than those encountered by their early European
      counterparts. The costs of transforming a lottery win to an actual diversity visa
      and Green Card are so high that only Africans in well-paying jobs, who are likely
      to be professionals rather than mere high school graduates, are likely to be able
      to afford the full costs of programme participation. In this sense, the programme
      has an in-built, skills-selective mechanism. The main objective of this study is
      to examine the extent to which the DV has facilitated the movement of
      professional, technical and kindred workers (PTKs) from Africa to the United
      States, and some of the economic and policy implications of the process.

PMID- 24899734
TI  - An automated system to mount cryo-cooled protein crystals on a synchrotron beam
      line, using compact sample cassettes and a small-scale robot.
AB  - An automated system for mounting and dismounting pre-frozen crystals has been
      implemented at the Stanford Synchrotron Radiation Laboratory (SSRL). It is based
      on a small industrial robot and compact cylindrical cassettes, each holding up to
      96 crystals mounted on Hampton Research sample pins. For easy shipping and
      storage, the cassette fits inside several popular dry-shippers and long-term
      storage Dewars. A dispensing Dewar holds up to three cassettes in liquid nitrogen
      adjacent to the beam line goniometer. The robot uses a permanent magnet tool to
      extract samples from, and insert samples into a cassette, and a cryo-tong tool to
      transfer them to and from the beam line goniometer. The system is simple, with
      few moving parts, reliable in operation and convenient to use.

PMID- 24899735
TI  - Professing faith, professing medicine: Physicians and the call to evangelize.
AB  - THE HIPPOCRATIC OATH TRADITIONALLY ESTABLISHES MEDICINE AS A PROFESSION: A
      career, or vocation based on the professing of an oath regarding personal and
      public behavior. For Catholic physicians, the commitments of the Oath of
      Hippocrates take on new meaning when seen in light of the promises made at
      Baptism and renewed every Easter. This paper, originally an address to medical
      students, considers the role of Catholic physicians as evangelizers, those who
      spread the message and values of the Gospel of Jesus Christ. 

PMID- 24899737
TI  - Heterologous embryo transfer: Magisterial answers and metaphysical questions.
AB  - The debate regarding the morality of heterologous embryo transfer (HET) as a
      solution for the fate of cryopreserved embryos remains active. This paper
      endeavors to show that the magisterial instructions on bioethical issues can only
      lead to the conclusion that HET is always morally illicit. I begin by showing
      that the text of Dignitas personae recognizes HET as a procedure accomplishing a
      procreative function, and I indicate that it is through gestation that this
      procreative function occurs. I further show that the previous Instruction, Donum
      vitae, implicitly points to an ontological or spiritual consideration at play
      during gestation. This consideration is likely related to the procreative
      function identified in Dignitas personae. Finally, I place these two textual
      arguments in the context of the debate concerning HET and conclude that
      metaphysical questions must be clarified in order for the immorality of HET to be
      understood from a suitable anthropological perspective and gain more widespread
      acceptance. 

PMID- 24899736
TI  - The syndemic of AIDS and STDS among MSM.
AB  - The spread of HIV and other STDs among men who have sex with men (MSM) has been
      labeled a syndemic because in this population a number of different and
      interrelated health problems have come together and interact with one another.
      The various elements of the syndemic have an additive effect, each one
      intensifying the others. These factors include the number of infectious diseases
      endemic in this population, the high rate of substance abuse problems and
      psychological disorders, and the significant percentage of MSM who have
      experienced childhood sexual abuse and other adverse events. While MSM are
      disproportionately affected by HIV, syphilis, and other STDs, health activists
      from the gay community have systematically resisted the application of the full
      range of public health strategies traditionally used to prevent their spread. In
      the more than three decades since the beginning of the HIV/AIDS epidemic, there
      have been substantial advances in testing and treatment, yet the infection rate
      among MSM, and particularly young MSM, remains high, even as it has been dropping
      among other risk groups. This paper deals with the history of the syndemic, the
      failure of various risk reduction strategies, and treatment as prevention. 

PMID- 24899738
TI  - Cultural competency, autonomy, and spiritual conflicts related to Reiki/CAM
      therapies: Should patients be informed?
AB  - The use of complementary and alternative medicines (CAM) such as Reiki is on the
      rise in healthcare centers. Reiki is associated with a spirituality that
      conflicts with some belief systems. Catholic healthcare facilities are restricted
      from offering this therapy because it conflicts with the teachings of the
      Catholic Church. However, hospitals are offering it without disclosing the
      spiritual aspects of it to patients. This article will address the ethical
      concerns and possible legal implications associated with the present process of
      offering Reiki. It will address these concerns based on the Joint Commission's
      Standard of Cultural Competency and the ethical principles of autonomy and
      informed consent. A proposal will also be introduced identifying specific
      information which Reiki/CAM practitioners should offer to their patients out of
      respect of their autonomy as well as their cultural, spiritual, and religious
      beliefs. 

PMID- 24899739
TI  - Current Medical ResearchWinter-Spring 2013.

PMID- 24899740
TI  - FAQs from the 2011 CMA Annual Conference.

PMID- 24899741
TI  - Challenged, yet filled with hope: Reflections from the CMA medical student boot
      camp.

PMID- 24899742
TI  - Plan B morning after pill.

PMID- 24899743
TI  - Leading birth control advocate recommends nuns take birth control.

PMID- 24899744
TI  - Practical resource for creating a Catholic living will.

PMID- 24899745
TI  - Catholic hospitals, are mergers the way to go?

PMID- 24899746
TI  - NARTH response to the WMA statement on natural variations of human sexuality.

PMID- 24899747
TI  - Prayer for a parent with a pierced and restless heart.

PMID- 24899748
TI  - Levonorgestrel in cases of rape: How does it work?
AB  - The Ethical and Religious Directives for Catholic Health Care Services allows the
      use of an emergency contraceptive for a woman who has been raped, as a defense
      against her attacker's sperm, provided the drug prevents fertilization and does
      not act against a conceived human life. Catholic emergency rooms around the
      country have been pressured to provide Plan B (LNG-EC) to patients seeking help
      after a sexual assault. Catholic bioethicists have supported the use of this drug
      based on their interpretation of the scientific literature regarding its
      mechanism of action. This paper presents a review of the mechanisms of action of
      LNG-EC when given during the fertile window, showing a high probability that it
      acts against human life rather than preventing fertilization, and proposes
      another class of drugs as a possible alternative. 

PMID- 24899749
TI  - Homosexual inclinations and the passions: A Thomistic theory of the psychogenesis
      of same-sex attraction disorder.
AB  - The Catholic Church has held that every human being is a child of God, and every
      person deserves to be treated with dignity and love regardless of their actions.
      The phrase "love the sinner, hate the sin" is a simple summary of the approach
      the Church takes to loving all human beings. The Church has also held firmly that
      both homosexual acts and homosexual inclinations are disordered, although the
      origins or contributing factors of homosexual inclinations are not entirely
      understood. In this paper, I apply principles from St. Thomas Aquinas's treatise
      on the passions to show that habitual mis-identification of the cause of pleasure
      associated with the apprehension of beauty, or misjudgments, may be involved in
      the psychogenesis of same-sex attraction disorder. 

PMID- 24899750
TI  - Prenatal chromosomal microarray for the Catholic physician.
AB  - Prenatal chromosomal microarray (CMA) is a test that is used to diagnose certain
      genetic problems in the fetus. While the test has been used in the pediatric
      setting for several years, it is now being introduced for use in the prenatal
      setting. The test offers great hope for detection of certain genetic defects in
      the fetus so that early intervention can be performed to improve the outcome for
      that individual. As with many biotechnical advances, CMA comes with certain
      bioethical issues that need to be addressed prior to its implementation. This
      paper is intended to provide guidance to all those that provide counseling
      regarding genetic testing options during pregnancy. 

PMID- 24899751
TI  - The healing community: A Catholic social justice critique of modern health care.
AB  - Catholic social thought calls for persons to be treated as subjects, not only as
      objects, and for a society in which basic health care is available to all.
      Treating the body as an object, isolated from other bodies and composed of many
      parts or systems, has led to great success in treating disease but has also
      degraded human dignity in patient care. Healthcare costs in the U.S. impede ready
      access to care, leading to financial collapse for millions each year; this is
      largely a generational result of rising expectations of long life for the elderly
      and widespread abortion of the very young (unborn); which practices follow in
      turn from the presumption that health results from human ingenuity and
      management. Catholic social thought affirms that love is essential to true health
      care and acknowledges that God is the source of healing. Such a perspective could
      point the way to humanizing the hospital experience and redressing the
      socioeconomic inequalities of modern health care. 

PMID- 24899752
TI  - Current medical researchSummer-Fall 2013.

PMID- 24899753
TI  - Densities, Excess Molar Volumes, and Thermal Expansion Coefficients of Aqueous
      Aminoethylethanolamine Solutions at Temperatures from 283.15 to 343.15 K.
AB  - The densities of aqueous mixtures of aminoethylethanolamine (CAS #000111-41-1)
      were measured over the entire compositional range at temperatures of 283.15
      343.15 K. The results of these measurements were used to calculate excess molar
      volumes and isobaric thermal expansion coefficients, and partial molar and
      apparent molar volumes and excess isobaric thermal expansion coefficients were
      subsequently derived. The excess molar volumes were correlated as a function of
      the mole fraction using the Redlich-Kister equation. Temperature dependences of
      the Redlich-Kister coefficients are also presented. The partial molar volumes at
      infinite dilution of AEEA in water were determined using two different methods.
      In addition, the solution density was correlated using a Joubian-Acree model.
      Aqueous solutions of AEEA exhibit similar properties to the aqueous solutions of
      other alkanolamines (like monoethanolamine) used in acid gas sweetening.

PMID- 24899754
TI  - Cataloging nocturia (circa 2014).

PMID- 24899756
TI  - Relationship between arousal intensity and heart rate response to arousal.
AB  - STUDY OBJECTIVES: The visual appearance of cortical arousals varies considerably,
      from barely meeting scoring criteria to very intense arousals. Arousal from sleep
      is associated with an increase in heart rate (HR). Our objective was to quantify
      the intensity of arousals in an objective manner using the time and frequency
      characteristics of the electroencephalogram (EEG) and to determine whether HR
      response to arousal correlates with arousal intensity so determined. DESIGN: Post
      hoc analysis of 20 preexisting polysomnography (PSG) files. SETTING: Research and
      Development Laboratory (YRT Limited). PARTICIPANTS: N/A. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Arousals were scored using the American Academy of
      Sleep Medicine criteria. The EEG signals' time and frequency characteristics were
      determined using wavelet analysis. An automatic algorithm was developed to scale
      arousal intensity based on the change in wavelet features and data from a
      training set obtained from 271 arousals visually scaled between zero and nine
      (most intense). There were 2,695 arousals in 20 PSGs that were scaled. HR
      response (DeltaHR) was defined as the difference between the highest HR in the
      interval [arousal-onset to (arousal-end +8 sec)] and the highest HR between 2 and
      12 sec preceding arousal onset. There was a strong correlation between arousal
      scale and DeltaHR within each subject (average r: 0.95 +/- 0.04). The slope of
      the relationship varied among subjects (0.7-2.4 min(-1)/unit scale). CONCLUSIONS:
      Arousal intensity, quantified by wavelet transform, is strongly associated with
      arousal-related tachycardia, and the gain of the relationship varies among
      subjects. Quantifying arousal intensity in PSGs provides additional information
      that may be clinically relevant.

PMID- 24899755
TI  - Pregabalin versus pramipexole: effects on sleep disturbance in restless legs
      syndrome.
AB  - STUDY OBJECTIVES: To compare pregabalin versus placebo and pramipexole for
      reducing restless legs syndrome (RLS)-related sleep disturbance. DESIGN:
      Randomized, double-blinded, crossover trial. SETTING: Twenty-three US sleep
      centers. PARTICIPANTS: Eighty-five individuals with moderate to severe idiopathic
      RLS and associated sleep disturbance. INTERVENTIONS: Participants were randomized
      across 6 treatment sequences comprising three 4-week periods on pregabalin 300
      mg/day (n = 75), pramipexole 0.5 mg/day (n = 76), or placebo (n = 73).
      MEASUREMENTS AND RESULTS: Polysomnography was conducted over 2 nights at the end
      of each period. Primary (wake after sleep onset [WASO], pregabalin vs placebo)
      and key secondary endpoints were analyzed for statistical significance, with
      descriptive statistics for other endpoints. Pregabalin improved sleep
      maintenance, demonstrated by reductions in WASO (-27.1 min vs placebo [P <
      0.0001]; -26.9 vs pramipexole) and number of awakenings after sleep onset (-2.7
      vs placebo; -7.9 vs pramipexole [P < 0.0001]) by polysomnography, and an increase
      in subjective total sleep time (30.8 min vs placebo [P < 0.0001]; 26.8 vs
      pramipexole). Pregabalin also increased slow wave sleep duration (20.9 min vs
      placebo; 32.1 vs pramipexole [P < 0.0001]). Reduction in periodic limb movement
      arousal index (PLMAI) with pregabalin was similar to pramipexole and greater than
      placebo (-3.7 PLMA/h [P < 0.0001]), although reduction in total PLM in sleep was
      less than for pramipexole. CONCLUSIONS: This study demonstrated improvements in
      objective and subjective measures of sleep maintenance and sleep architecture
      with pregabalin compared with placebo and pramipexole. Effects of pregabalin on
      periodic limb movement arousal index were comparable to pramipexole. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier, NCT00991276;
      http://clinicaltrials.gov/show/NCT00991276.

PMID- 24899757
TI  - Associations of objectively and subjectively measured sleep quality with
      subsequent cognitive decline in older community-dwelling men: the MrOS sleep
      study.
AB  - STUDY OBJECTIVES: To examine associations of objectively and subjectively
      measured sleep with subsequent cognitive decline. DESIGN: A population-based
      longitudinal study. SETTING: Six centers in the United States. PARTICIPANTS:
      Participants were 2,822 cognitively intact community-dwelling older men (mean age
      76.0 +/- 5.3 y) followed over 3.4 +/- 0.5 y. INTERVENTIONS: None. MEASUREMENTS
      AND RESULTS: OBJECTIVELY MEASURED SLEEP PREDICTORS FROM WRIST ACTIGRAPHY: total
      sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of
      long wake episodes (LWEP). Self-reported sleep predictors: sleep quality
      (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness
      Scale [ESS]), TST. Clinically significant cognitive decline: five-point decline
      on the Modified Mini-Mental State examination (3MS), change score for the Trails
      B test time in the worse decile. Associations of sleep predictors and cognitive
      decline were examined with logistic regression and linear mixed models. After
      multivariable adjustment, higher levels of WASO and LWEP and lower SE were
      associated with an 1.4 to 1.5-fold increase in odds of clinically significant
      decline (odds ratio 95% confidence interval) Trails B test: SE < 70% versus SE >=
      70%: 1.53 (1.07, 2.18); WASO >= 90 min versus WASO < 90 min: 1.47 (1.09, 1.98);
      eight or more LWEP versus fewer than eight: 1.38 (1.02, 1.86). 3MS: eight or more
      LWEP versus fewer than eight: 1.36 (1.09, 1.71), with modest relationships to
      linear change in cognition over time. PSQI was related to decline in Trails B
      performance (3 sec/y per standard deviation increase). CONCLUSIONS: Among older
      community-dwelling men, reduced sleep efficiency, greater nighttime wakefulness,
      greater number of long wake episodes, and poor self-reported sleep quality were
      associated with subsequent cognitive decline.

PMID- 24899759
TI  - Behavioral treatment of chronic insomnia in older adults: does nocturia matter?
AB  - OBJECTIVE: To evaluate the impact of nocturia on the therapeutic response of
      chronic insomnia to behavioral treatment in older adults. METHODS: Secondary
      analysis of a randomized clinical trial designed to assess the efficacy of brief
      behavioral treatment of insomnia (BBTI) vs. an information-only control (IC) in
      79 community-dwelling older adults with chronic insomnia. For the current
      analysis, participants were stratified into 2 groups: those with self-reported
      nocturia at baseline i.e., >= 1 void/night (N = 30; 16 IC, 14 BBTI) and those
      without nocturia (N = 49; 24 IC, 25 BBTI). We then determined the impact of BBTI
      on sleep, sleep quality, and nocturia as assessed by self-report, actigraphy, and
      polysomnography. RESULTS: Individuals without baseline nocturia responded well to
      BBTI with significant decrease in sleep latency, wake after sleep onset, and
      total sleep time assessed by sleep diary and actigraphy; these changes were
      significantly greater than those in the IC group. In comparison, changes in the
      same sleep parameters among participants with nocturia were not significantly
      different from the IC control. Although BBTI showed significant improvement in
      sleep quality in groups with and without nocturia (as assessed by PSQI and sleep
      diary), the effect size of these improvements was larger in those without
      nocturia than in those with nocturia (PSQI d = 0.82 vs. 0.53, diary sleep quality
      d = 0.83 vs. 0.51). CONCLUSIONS: These secondary analyses suggest that brief
      behavioral treatment of insomnia may be more efficacious in improving insomnia in
      participants without nocturia. Addressing nocturia may improve the efficacy of
      behavioral insomnia treatment.

PMID- 24899758
TI  - Retrospective population cohort study on hip fracture risk associated with
      zolpidem medication.
AB  - STUDY OBJECTIVE: Few studies have evaluated the hip fracture risk for zolpidem
      users. We assessed the risk for subjects taking zolpidem. DESIGN: Population
      based retrospective cohort study using claims data of a universal insurance
      system. PARTICIPANTS: We identified 6,978 patients newly prescribed for zolpidem
      in 2000-2001 age 18 y and older, and 27,848 nonusers frequency matched with sex,
      age, and date visiting a clinic. MEASUREMENTS AND RESULTS: Both cohorts were
      followed up to the end of 2008 to measure the hip fracture incidence and risk,
      which considered factors such as sex, age, occupation, days of drug use, and
      osteoporosis status. The zolpidem users had a 2.23-fold higher hip fracture
      incidence than nonusers (3.10 versus 1.39 per 1,000 person-y). The risk increased
      with age for both cohorts. The elderly users had a 21-fold higher incidence than
      the younger users, or twofold higher than the elderly nonusers. Among 33 patients
      (20.4%) with hip fracture occurring during presumed medication days, which was
      accountable for an incidence of 1,083.0 per 1,000 person-y. Those taking the
      medicine for 8 days or longer had a moderately higher fracture rate than those
      taking it for less days (6.02 versus 4.48 per 100 person-times) with a ratio of
      1.34 (95% confidence interval 0.42-4.56). Subjects with blue collar occupations
      were at a higher fracture risk. CONCLUSION: The hip fracture risk of zolpidem
      users is higher than that of nonusers. Fracture prevention awareness should be
      disseminated to the users.

PMID- 24899760
TI  - Brown Norway and Zucker Lean rats demonstrate circadian variation in ventilation
      and sleep apnea.
AB  - STUDY OBJECTIVES: Circadian rhythms influence many biological systems, but there
      is limited information about circadian and diurnal variation in sleep related
      breathing disorder. We examined circadian and diurnal patterns in sleep apnea and
      ventilatory patterns in two rat strains, one with high sleep apnea propensity
      (Brown Norway [BN]) and the other with low sleep apnea propensity (Zucker Lean
      [ZL]). DESIGN/SETTING: Chronically instrumented rats were randomized to breathe
      room air (control) or 100% oxygen (hyperoxia), and we performed 20-h
      polysomnography beginning at Zeitgeber time 4 (ZT 4; ZT 0 = lights on, ZT12 =
      lights off). We examined the effect of strain and inspired gas (twoway analysis
      of variance) and analyzed circadian and diurnal variability. MEASUREMENTS AND
      RESULTS: Strain and inspired gas-dependent differences in apnea index (AI;
      apneas/h) were particularly prominent during the light phase. AI in BN rats
      (control, 16.9 +/- 0.9; hyperoxia, 34.0 +/- 5.8) was greater than in ZL rats
      (control, 8.5 +/- 1.0; hyperoxia, 15.4 +/- 1.1, [strain effect, P < 0.001; gas
      effect, P = 0.001]). Hyperoxia reduced respiratory frequency in both strains, and
      all respiratory pattern variables demonstrated circadian variability. BN rats
      exposed to hyperoxia demonstrated the largest circadian fluctuation in AI
      (amplitude = 17.9 +/- 3.7 apneas/h [strain effect, P = 0.01; gas effect, P <
      0.001; interaction, P = 0.02]; acrophase = 13.9 +/- 0.7 h; r (2) = 0.8 +/- 1.4).
      CONCLUSIONS: Inherited, environmental, and circadian factors all are important
      elements of underlying sleep related breathing disorder. Our method to examine
      sleep related breathing disorder phenotypes in rats may have implications for
      understanding vulnerability for sleep related breathing disorder in humans.

PMID- 24899761
TI  - Abnormal myelin and axonal integrity in recently diagnosed patients with
      obstructive sleep apnea.
AB  - STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) show significant
      white matter injury; whether that injury represents myelin or axonal damage is
      unclear. The objective was to examine myelin and axonal changes in patients with
      newly diagnosed OSA over control subjects. DESIGN: Cross-sectional study.
      SETTING: University-based medical center. PARTICIPANTS: Twenty-three newly
      diagnosed, treatment-naive OSA and 23 age- and sex-matched control subjects.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Radial and axial diffusivity maps,
      calculated from diffusion tensor imaging data (3.0 Tesla MRI scanner), indicating
      diffusion perpendicular (myelin status) or parallel (axonal status) to fibers,
      respectively, were normalized, smoothed, and compared between groups (analysis of
      covariance; covariate: age). Global brain radial and axial diffusivity values,
      and global brain volume with myelin and axonal changes were determined, and
      region-of-interest analyses performed in areas of significant differences between
      groups based on voxel-based procedures. Global radial and axial diffusivity
      values were significantly reduced in OSA versus control subjects (radial, P =
      0.004; axial, P = 0.019), with radial (myelin) diffusivity reduced more than
      axial (axonal), and more left-sided reduction for both measures. Localized
      declines for myelin and axonal measures appeared in the dorsal and ventral
      medulla, cerebellar cortex and deep nuclei, basal ganglia, hippocampus, amygdala,
      corpus callosum, insula, cingulate and medial frontal cortices, and other
      cortical areas (P < 0.005), all regions mediating functions affected in OSA.
      CONCLUSIONS: Fiber injury appears in critical medullary respiratory regulatory
      sites, as well as cognitive and autonomic control areas. Myelin is more affected
      in newly diagnosed OSA than axons, and primarily on the left side, possibly from
      the increased myelin sensitivity to hypoxia and asymmetric perfusion.

PMID- 24899762
TI  - Continuous positive airway pressure increases pulsatile growth hormone secretion
      and circulating insulin-like growth factor-1 in a time-dependent manner in men
      with obstructive sleep apnea: a randomized sham-controlled study.
AB  - STUDY OBJECTIVES: To assess the time-dependent effect of continuous positive
      airway pressure (CPAP), on insulin-like growth factor-1 (IGF-1), IGF binding
      proteins (IGFBPs) and pulsatile growth hormone (GH) secretion. DESIGN: A
      randomized, double-blind, sham-controlled, parallel group study. PARTICIPANTS:
      Sixty-five middle-aged men with moderate to severe obstructive sleep apnea.
      INTERVENTION: Active (n = 34) or sham (n = 31) CPAP for 12 weeks, followed by 12
      weeks of active CPAP (n = 65). MEASUREMENTS AND RESULTS: Fasting morning IGF-1,
      IGFBP-3, and IGFBP-1 blood levels at 0, 6, 12, and 24 weeks. Overnight GH
      secretion was calculated by mathematical deconvolution of serial GH measurements
      from serum samples collected every 10 min (22:00-06:00) during simultaneous
      polysomnography in a subset of 18 men (active n = 11, sham n = 7) at week 12.
      Active, compared with sham, CPAP increased IGF-1 at 12 weeks (P = 0.006), but not
      at 6 weeks (P = 0.44). Changes in IGFBP-3 and IGFBP-1 were not different between
      groups at 6 or 12 weeks (all P >= 0.15). At week 24, there was a further increase
      in IGF-1 and a decrease in IGFBP-1 in the pooled group (P = 0.0001 and 0.046,
      respectively). In the subset, total (P = 0.001) and pulsatile (P = 0.002) GH
      secretion, mean GH concentration (P = 0.002), mass of GH secreted per pulse (P =
      0.01) and pulse frequency (P = 0.04) were all higher after 12 weeks of CPAP
      compared with sham. Basal secretion, interpulse regularity, and GH regularity
      were not different between groups (all P > 0.11). CONCLUSIONS: Twelve weeks, but
      not 6 weeks, of CPAP increases IGF-1, with a further increase after 24 weeks.
      Total and pulsatile GH secretion, secretory burst mass and pulse frequency are
      also increased by 12 weeks. CPAP improves specific elements of the GH/IGF-1 axis
      in a time-dependent manner. CLINICAL TRIALS REGISTRATION: Australia New Zealand
      Clinical Trials Network, www.anzctr.org.au, number ACTRN12608000301369.

PMID- 24899763
TI  - Recovery of neurological function despite immediate sleep disruption following
      diffuse brain injury in the mouse: clinical relevance to medically untreated
      concussion.
AB  - STUDY OBJECTIVE: We investigated the relationship between immediate disruption of
      posttraumatic sleep and functional outcome in the diffuse brain-injured mouse.
      DESIGN: Adult male C57BL/6 mice were subjected to moderate midline fluid
      percussion injury (n = 65; 1.4 atm; 6-10 min righting reflex time) or sham injury
      (n = 44). Cohorts received either intentional sleep disruption (minimally
      stressful gentle handling) or no sleep disruption for 6 h following injury.
      Following disruption, serum corticosterone levels (enzyme-linked immunosorbent
      assay) and posttraumatic sleep (noninvasive piezoelectric sleep cages) were
      measured. For 1-7 days postinjury, sensorimotor outcome was assessed by Rotarod
      and a modified Neurological Severity Score (NSS). Cognitive function was measured
      using Novel Object Recognition (NOR) and Morris water maze (MWM) in the first
      week postinjury. SETTING: Neurotrauma research laboratory. MEASUREMENTS AND
      RESULTS: Disrupting posttraumatic sleep for 6 h did not affect serum
      corticosterone levels or functional outcome. In the hour following the first dark
      onset, sleep-disrupted mice exhibited a significant increase in sleep; however,
      this increase was not sustained and there was no rebound of lost sleep.
      Regardless of sleep disruption, mice showed a time-dependent improvement in
      Rotarod performance, with brain-injured mice having significantly shorter
      latencies on day 7 compared to sham. Further, brain-injured mice, regardless of
      sleep disruption, had significantly higher NSS scores postinjury compared with
      sham. Cognitive behavioral testing showed no group differences among any
      treatment group measured by MWM and NOR. CONCLUSION: Short-duration disruption of
      posttraumatic sleep did not affect functional outcome, measured by motor and
      cognitive performance. These data raise uncertainty about posttraumatic sleep as
      a mechanism of recovery from diffuse brain injury.

PMID- 24899764
TI  - Ecology and neurophysiology of sleep in two wild sloth species.
AB  - STUDY OBJECTIVES: Interspecific variation in sleep measured in captivity
      correlates with various physiological and environmental factors, including
      estimates of predation risk in the wild. However, it remains unclear whether
      prior comparative studies have been confounded by the captive recording
      environment. Herein we examine the effect of predation pressure on sleep in
      sloths living in the wild. DESIGN: Comparison of two closely related sloth
      species, one exposed to predation and one free from predation. SETTING:
      Panamanian mainland rainforest (predators present) and island mangrove (predators
      absent). PARTICIPANTS: Mainland (Bradypus variegatus, five males and four
      females) and island (Bradypus pygmaeus, six males) sloths. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Electroencephalographic (EEG) and electromyographic
      (EMG) activity was recorded using a miniature data logger. Although both species
      spent between 9 and 10 h per day sleeping, the mainland sloths showed a
      preference for sleeping at night, whereas island sloths showed no preference for
      sleeping during the day or night. Standardized EEG activity during nonrapid eye
      movement (NREM) sleep showed lower low-frequency power, and increased spindle and
      higher frequency power in island sloths when compared to mainland sloths.
      CONCLUSIONS: In sloths sleeping in the wild, predation pressure influenced the
      timing of sleep, but not the amount of time spent asleep. The preference for
      sleeping at night in mainland sloths may be a strategy to avoid detection by
      nocturnal cats. The pronounced differences in the NREM sleep EEG spectrum remain
      unexplained, but might be related to genetic or environmental factors.

PMID- 24899769
TI  - Is a Response to Intervention (RTI) Approach to Preschool Language and Early
      Literacy Instruction Needed?
AB  - Preschool experience plays a role in children's development. However, for
      programs with language and early literacy goals, the question remains whether or
      not preschool instructional experiences are sufficiently effective to achieve
      these goals for all children. In a multisite study, we conducted a process
      product description of preschool instruction and children's growth and outcomes
      in typical programs (i.e., Pre-Kindergarten, Title 1, Head Start, Tuition-Based)
      using a Response to Intervention (RTI) perspective. Results indicated that (a)
      students in their preschool year prior to kindergarten made small gains, but
      students starting the year in lower Tier 2 and 3 performance levels did not close
      initial skills gaps, (b) variations were noted by program types with varying
      socio-demographics and instructional processes, and (c) the quality of
      instruction (Tier 1) received by all was low with room for improvement.
      Implications for future research on the application of the RTI approach and
      potential benefits are discussed.

PMID- 24899768
TI  - Rapid tolerance development to the NREM sleep promoting effect of alcohol.
AB  - STUDY OBJECTIVES: Alcohol tolerance is a major contributor towards the
      development of alcohol dependence. Does alcohol intake result in rapid tolerance
      development to alcohol induced NREM sleep promotion? This has never been
      examined. Our objective was to examine whether two bouts of alcohol consumption
      on consecutive days results in rapid tolerance development to alcohol-induced
      NREM sleep promotion. DESIGN: N/A. SETTING: N/A. PATIENTS OR PARTICIPANTS:
      C57BL/6J mice. INTERVENTIONS: Mice (N = 5) were implanted with sleep electrodes
      using standard surgical conditions. Following postoperative recovery and
      habituation, the experiment was begun. On baseline day, water bottle changes were
      performed at 10:00 (3 h after dark onset) and 14:00 to mimic conditions during
      alcohol consumption days. On next 2 days, (Days 1 and 2) mice were allowed to
      self-administer alcohol (20% v/v) for 4 h beginning at 10:00 and ending at 14:00.
      Sleep-wakefulness was continuously recorded from 10:00 to 18:00 (8 h; 4 h during
      alcohol + 4 h post-alcohol) on all 3 days. MEASUREMENTS AND RESULTS: Although
      mice consumed comparable amounts of alcohol on Days 1 and 2, NREM sleep and
      wakefulness were significantly and differentially affected during 4 h post
      alcohol period. A robust alcohol-induced NREM sleep promotion was observed on Day
      1. However, no such sleep promotion was observed on Day 2, suggesting rapid
      tolerance development. CONCLUSIONS: Our study is the first to demonstrate that
      alcohol consumption for two consecutive days results in development of rapid
      tolerance to alcohol-induced sleep promotion.

PMID- 24899766
TI  - Glucose and fat metabolism in narcolepsy and the effect of sodium oxybate: a
      hyperinsulinemic-euglycemic clamp study.
AB  - INTRODUCTION: Narcolepsy is associated with obesity though it is uncertain
      whether this is caused by changes in glucose and fat metabolism. Therefore, we
      performed a detailed analysis of systemic energy homeostasis in narcolepsy
      patients, and additionally, investigated whether it was affected by three months
      of sodium oxybate (SXB) treatment. METHODS: Nine hypocretin deficient patients
      with narcolepsy-cataplexy, and nine healthy sex, age, and BMI matched controls
      were enrolled. A hyperinsulinemic-euglycemic clamp combined with stable isotopes
      ([6,6-(2)H2]-glucose and [(2)H5]- glycerol) was performed at baseline. In seven
      patients a second study was performed after three months of SXB treatment.
      RESULTS: Glucose disposal rate (GDR) per unit serum insulin was significantly
      higher in narcolepsy patients compared to matched controls (1.6 +/- 0.2 vs. 1.1
      +/- 0.3 MUmol/kgFFM/min/mU*L; P = 0.024), whereas beta-cell function was similar
      (P = 0.50). Basal steady state glycerol appearance rate tended to be lower in
      narcolepsy patients (5.2 +/- 0.4 vs. 7.5 +/- 1.3 MUmol/kgFM/min; P = 0.058),
      suggesting a lower rate of lipolysis. SXB treatment induced a trend in reduction
      of the GDR (1.4 +/- 0.1 vs. 1.1 +/- 0.2 MUmol/kgFFM/min/mU*L; P = 0.063) and a
      reduction in endogenous glucose production (0.24 +/- 0.03 vs. 0.16 +/- 0.03
      MUmol/kgFFM/min/mU*L: P = 0.028) per unit serum insulin. After SXB treatment
      lipolysis increased (4.9 +/- 0.4 vs. 6.5 +/- 0.6 MUmol/kgFM/min; P = 0.018), and
      body weight decreased in narcolepsy patients (99.2 +/- 6.0 vs. 94.0 +/- 5.4 kg; P
      = 0.044). CONCLUSION: We show that narcolepsy patients are more insulin sensitive
      and may have a lower rate of lipolysis than matched controls. SXB stimulated
      lipolysis in narcolepsy patients, possibly accounting for the weight loss after
      treatment. While sodium oxybate tended to decrease systemic insulin sensitivity,
      it increased hepatic insulin sensitivity, suggesting tissue-specific effects.

PMID- 24899765
TI  - Altered emotion perception in insomnia disorder.
AB  - STUDY OBJECTIVES: Chronic insomnia is a prevalent sleep disorder that negatively
      affects daytime functioning and confers risk for the future development of
      psychiatric disorder. Patients with insomnia often report problems with emotion
      regulation and impaired social interactions. Moreover, experimental sleep loss in
      healthy adults is associated with altered reactivity to and interpretation of
      emotional information. In the current study, we investigated socioemotional
      processing in patients with chronic insomnia disorder relative to healthy good
      sleepers. DESIGN: Between-groups comparison. SETTING: Sleep Research Laboratory.
      PARTICIPANTS: Patients with well-defined psychophysiological insomnia (PI; n =
      16), free from psychiatric disorder, and an age- and sex-matched control group of
      good sleepers (GS; n = 15). INTERVENTIONS: N/A. MEASUREMENT AND RESULTS: All
      participants completed a facial expression recognition task, between 18:00 and
      19:00, requiring participants to categorize and rate the intensity of four
      emotional expression categories: anger, fear, happiness, and sadness. People with
      PI did not differ from GS with respect to categorization of facial expressions.
      However, in terms of intensity judgements, across all emotion categories,
      patients tended to rate faces as less emotionally intense (Cohen's d = 0.70).
      Specifically, they rated expressions displaying sadness and fear as significantly
      less emotionally intense than healthy GS (both P < 0.05; Cohen's d = 0.77 and
      0.89, respectively). Measures of sleepiness (Psychomotor Vigilance Test,
      Karolinska Sleepiness Scale) or self-reported sleep were not reliably associated
      with emotional intensity ratings. However, anxiety and depression were negatively
      related to intensity ratings. CONCLUSION: For the first time we show that chronic
      insomnia is associated with reduced ratings of emotion intensity for face
      expressions displaying sadness and fear. Further work is required to elucidate
      possible mechanisms and pathways underlying insomnia-related emotional
      impairment.

PMID- 24899767
TI  - Trazodone increases the respiratory arousal threshold in patients with
      obstructive sleep apnea and a low arousal threshold.
AB  - STUDY OBJECTIVES: The effect of common sedatives on upper airway physiology and
      breathing during sleep in obstructive sleep apnea (OSA) has been minimally
      studied. Conceptually, certain sedatives may worsen OSA in some patients.
      However, sleep and breathing could improve with certain sedatives in patients
      with OSA with a low respiratory arousal threshold. This study aimed to test the
      hypothesis that trazodone increases the respiratory arousal threshold in patients
      with OSA and a low arousal threshold. Secondary aims were to examine the effects
      of trazodone on upper airway dilator muscle activity, upper airway
      collapsibility, and breathing during sleep. DESIGN: Patients were studied on 4
      separate nights according to a within-subjects cross-over design. SETTING: Sleep
      physiology laboratory. PATIENTS: Seven patients with OSA and a low respiratory
      arousal threshold. INTERVENTIONS: In-laboratory polysomnograms were obtained at
      baseline and after 100 mg of trazodone was administered, followed by detailed
      overnight physiology experiments under the same conditions. During physiology
      studies, continuous positive airway pressure was transiently lowered to measure
      arousal threshold (negative epiglottic pressure prior to arousal), dilator muscle
      activity (genioglossus and tensor palatini), and upper airway collapsibility
      (Pcrit). MEASUREMENTS AND RESULTS: Trazodone increased the respiratory arousal
      threshold by 32 +/- 6% (-11.5 +/- 1.4 versus -15.3 +/- 2.2 cmH2O, P < 0.01) but
      did not alter the apnea-hypopnea index (39 +/- 12 versus 39 +/- 11 events/h
      sleep, P = 0.94). Dilator muscle activity and Pcrit also did not systematically
      change with trazodone. CONCLUSIONS: Trazodone increases the respiratory arousal
      threshold in patients with obstructive sleep apnea and a low arousal threshold
      without major impairment in dilator muscle activity or upper airway
      collapsibility. However, the magnitude of change in arousal threshold was
      insufficient to overcome the compromised upper airway anatomy in these patients.

PMID- 24899770
TI  - International arrivals: widespread bioinvasions in European Seas.
AB  - The European Union lacks a comprehensive framework to address the threats posed
      by the introduction and spread of marine non-indigenous species (NIS). Current
      efforts are fragmented and suffer substantial gaps in coverage. In this paper we
      identify and discuss issues relating to the assessment of spatial and temporal
      patterns of introductions in European Seas (ES), based on a scientifically
      validated information system of aquatic non-indigenous and cryptogenic species,
      AquaNIS. While recognizing the limitations of the existing data, we extract
      information that can be used to assess the relative risk of introductions for
      different taxonomic groups, geographic regions and likely vectors. The dataset
      comprises 879 multicellular NIS. We applied a country-based approach to assess
      patterns of NIS richness in ES, and identify the principal introduction routes
      and vectors, the most widespread NIS and their spatial and temporal spread
      patterns. Between 1970 and 2013, the number of recorded NIS has grown by 86, 173
      and 204% in the Baltic, Western European margin and the Mediterranean,
      respectively; 52 of the 879 NIS were recorded in 10 or more countries, and 25 NIS
      first recorded in European seas since 1990 have since been reported in five or
      more countries. Our results highlight the ever-rising role of shipping
      (commercial and recreational) as a vector for the widespread and recently spread
      NIS. The Suez Canal, a corridor unique to the Mediterranean, is responsible for
      the increased introduction of new thermophilic NIS into this warming sea. The
      2020 goal of the EU Biodiversity Strategy concerning marine Invasive Alien
      Species may not be fully attainable. The setting of a new target date should be
      accompanied by scientifically robust, sensible and pragmatic plans to minimize
      introductions of marine NIS and to study those present.

PMID- 24899771
TI  - The uefa euro 2012 anti-doping programme - scientific review.
AB  - The final tournament of the UEFA European Football Championship is one of the top
      sporting events in the world, and a high-profile event of this kind requires a
      well-planned and well-executed anti-doping programme to ensure the integrity of
      results in the competition. UEFA EURO 2012 presented a unique logistical
      challenge, with the tournament spread across two countries, both covering a large
      geographical area. This paper discusses the planning and delivery of both the pre
      tournament out-of-competition (OOC) testing programme and the in-competition (IC)
      programme, as well as reviewing the activities of doping control officers (DCOs),
      the whereabouts programme and assessing the sample collection and transport
      process. The analytical approach applied is also discussed, along with an
      overview of the distribution of T/E ratios and blood parameters. 

PMID- 24899772
TI  - Investigation of urinary excretion of hydroxyethyl starch and dextran by uhplc
      hrms in different acquisition modes.
AB  - Plasma volume expanders (PVEs) such as hydroxyethyl starch (HES) and dextran are
      misused in sports because they can prevent dehydration and reduce haematocrit
      values to mask erythropoietin abuse. Endogenous hydrolysis generates multiple HES
      and dextran oligosaccharides which are excreted in urine. Composition of the
      urinary metabolic profiles of PVEs varies depending on post-administration time
      and can have an impact on their detectability. In this work, different mass
      spectrometry data acquisition modes (full scan with and without in-source
      collision-induced dissociation) were used to study urinary excretion profiles of
      HES and dextran, particularly by investigating time-dependent detectability of
      HES and dextran urinary oligosaccharide metabolites in post-administration
      samples. In-source fragmentation yielded the best results in terms of limit of
      detection (LOD) and detection times, whereas detection of HES and dextran
      metabolites in full scan mode with no in-source fragmentation is related to
      recent administration (< 24 hours). Urinary excretion studies showed detection
      windows for HES and dextran respectively of 72 and 48 hours after administration.
      Dextran concentrations were above the previously proposed threshold of 500 ug .
      mL(-1) for 12 hours. A "dilute-and-shoot" method for the detection of HES and
      dextran in human urine by ultra-high-pressure liquid chromatography-electrospray
      ionization-high resolution OrbitrapTM mass spectrometry was developed for this
      study. Validation of the method showed an LOD in the range of 10-500 ug . mL(-1)
      for the most significant HES and dextran metabolites in the different modes. The
      method allows retrospective data analysis and can be implemented in existing high
      resolution mass spectrometry-based doping control screening analysis. 

PMID- 24899773
TI  - Actn3 genotype is associated with testosterone levels of athletes.
AB  - alpha-Actinin-3 (ACTN3) has been proposed to regulate skeletal muscle
      differentiation and hypertrophy through its interaction with the signalling
      protein calcineurin. Since the inhibition of calcineurin potentiates the
      production of testosterone, we hypothesized that alpha-actinin-3 deficiency
      (predicted from the ACTN3 XX genotype) may influence serum levels of testosterone
      of athletes. OBJECTIVE: To investigate the association of ACTN3 gene R577X
      polymorphism with resting testosterone levels in athletes. METHODS: A total of
      209 elite Russian athletes from different sports (119 males, 90 females) were
      genotyped for ACTN3 gene R577X polymorphism by real-time PCR. Resting
      testosterone was examined in serum of athletes using enzyme immunoassay. RESULTS:
      The mean testosterone levels were significantly higher in both males and females
      with the ACTN3 R allele than in XX homozygotes (males: RR: 24.9 (5.7), RX: 21.8
      (5.5), XX: 18.6 (4.9) ng . mL(-1), P = 0.0071; females: RR: 1.43 (0.6), RX: 1.21
      (0.71), XX: 0.79 (0.66) ng . mL(-1), P = 0.0167). CONCLUSIONS: We found that the
      ACTN3 R allele was associated with high levels of testosterone in athletes, and
      this may explain, in part, the association between the ACTN3 RR genotype,
      skeletal muscle hypertrophy and power athlete status.

PMID- 24899774
TI  - Bdkrb2 gene -9/+9 polymorphism and swimming performance.
AB  - The aim of the study was to evaluate the association between swimming performance
      and the -9/+9 (rs5810761) polymorphism within the BDKRB2 gene in successful
      competitive swimmers. Best individual swimming results expressed in FINA points
      achieved at short, middle and long distance events of 157 well-trained Polish
      swimmers were incorporated into an analysis. Athletes' genotype and allele
      distributions were analysed in comparison to 230 unrelated sedentary subjects who
      served as controls with the chi(2) test. All samples were genotyped for the
      BDKRB2 -9/+9 polymorphism using the polymerase chain reaction (PCR). The effects
      of genotype on swimming performance were analysed with two-way (3 x 2; genotype x
      gender) analysis of variance with metrical age as a covariate for each distance
      specialization. No statistical differences in the genotype and allele frequencies
      were found in long distance swimmers when compared with the total group of
      swimmers or controls. The BDKRB2 +9/-9 genotype had no significant effect on
      swimming performance at short, middle or long distance, regardless of gender. The
      results of this study do not support the hypothesis that the BDKRB2 -9/+9
      polymorphism is associated with swimming performance in Polish swimmers. 

PMID- 24899775
TI  - NO ASSOCIATION BETWEEN tHbmass AND POLYMORPHISMS IN THE HBB GENE IN ENDURANCE
      ATHLETES.
AB  - The aim of this study was to examine the association between tHbmass and HBB gene
      polymorphisms in athletes of endurance disciplines. Eighty-two well-trained
      athletes (female n=36, male n=46), aged 19.3 +/- 2.7 years, representing cross
      country skiing (n=37) and middle- and long-distance running (n=45), participated
      in the study. Genotyping for 2 polymorphisms in the HBB gene (- 551C/T and intron
      2, +16 C/G) was performed using restriction fragment length polymorphism
      analysis. Total haemoglobin mass (tHbmass) was determined by the optimized carbon
      monoxide rebreathing method. Blood morphology, indices of iron status (ferritin,
      transferrin receptor and total iron binding capacity) and C reactive protein were
      also determined. No differences were found in the HBB genotype and allele
      frequencies between male and female athletes. Regardless of the polymorphisms, no
      relationships were found between HBB genotypes as well as alleles and relative
      values of tHbmass, expressed per body mass (g . kg(-1) BM), both in female and
      male athletes. Our results demonstrated that -551 C/T and intron 2, +16 C/G
      polymorphisms of the HBB gene have no association with total haemoglobin mass in
      endurance athletes. It cannot be ruled out that several polymorphisms, each with
      a small but significant contribution, may be responsible for the amount of
      haemoglobin. 

PMID- 24899776
TI  - Blood flow restricted resistance training attenuates myostatin gene expression in
      a patient with inclusion body myositis.
AB  - Inclusion body myositis is a rare idiopathic inflammatory myopathy that produces
      extreme muscle weakness. Blood flow restricted resistance training has been shown
      to improve muscle strength and muscle hypertrophy in inclusion body myositis.
      OBJECTIVE: The aim of this study was to evaluate the effects of a resistance
      training programme on the expression of genes related to myostatin (MSTN)
      signalling in one inclusion body myositis patient. METHODS: A 65-year-old man
      with inclusion body myositis underwent blood flow restricted resistance training
      for 12 weeks. The gene expression of MSTN, follistatin, follistatin-like 3,
      activin II B receptor, SMAD-7, MyoD, FOXO-3, and MURF-2 was quantified. RESULTS:
      After 12 weeks of training, a decrease (25%) in MSTN mRNA level was observed,
      whereas follistatin and follistatin-like 3 gene expression increased by 40% and
      70%, respectively. SMAD-7 mRNA level was augmented (20%). FOXO-3 and MURF-2 gene
      expression increased by 40% and 20%, respectively. No change was observed in
      activin II B receptor or MyoD gene expression. CONCLUSIONS: Blood flow restricted
      resistance training attenuated MSTN gene expression and also increased expression
      of myostatin endogenous inhibitors. Blood flow restricted resistance training
      evoked changes in the expression of genes related to MSTN signalling pathway that
      could in part explain the muscle hypertrophy previously observed in a patient
      with inclusion body myositis.

PMID- 24899777
TI  - Endocrine response to an ultra-marathon in pre- and post-menopausal women.
AB  - Ultra-endurance competitions are becoming increasingly popular but there is
      limited research on female participants. The purpose of this study was to examine
      changes in estrogen and the IGF-I system in women after an ultra-marathon. Six
      pairs of pre- and post- menopausal women were matched for race finish times;mean
      finish time was 20 hours. Blood samples were drawn 24 hours before the race, at
      the finish, and 24 hours into recovery. Samples were analysed for estradiol,
      total IGF-I, IGFBP-1, and intact IGFBP-3. There was a significant increase in
      estradiol following the race in both groups (P < 0.05). Total IGF-I decreased
      after the race (P < 0.01) and remained lower in recovery. IGFBP-1 increased after
      the race (P < 0.001) but returned to pre-race levels after 24 hours, while intact
      IGFBP-3 was significantly lower post-race and in recovery (P < 0.001).
      Postmenopausal women had significantly lower estradiol at baseline, but there
      were no other group differences. These results demonstrate that among
      recreational female runners, an ultra-marathon is associated with IGF system
      changes that are consistent with an energy-deficient, catabolic state. Further
      research is needed to confirm the effect of these endocrine changes on health and
      performance. 

PMID- 24899778
TI  - The influence of thyroid function and bone turnover on lipoprotein profile in
      young physically active men with different insulin sensitivity.
AB  - Physical activity induces changes in the endocrine system. Previous data
      indicated that changes in insulin secretion and the tissue response to this
      hormone are very important for energy metabolism. It is believed that they are
      accompanied by changes in lipid metabolism, but factors contributing to this
      process are still disputed. The aim of this study was to assess interactions
      among insulin sensitivity, thyroid function, a bone turnover marker and serum
      lipid profile in young physically active men. Eighty-seven physical education
      students, aged 18-23 years, participated in the study. We measured serum levels
      of glucose, lipids, insulin, thyroid-stimulating hormone (TSH), osteocalcin and
      anthropometric parameters. Insulin sensitivity was determined using homeostatic
      model assessment for insulin resistance (HOMA-IR). The median value of HOMA-IR
      (1.344) was used to divide the study population into Group A (above the median)
      and Group B (below the median). Men from both groups did not differ in
      anthropometric parameters or in daily physical activity. Triglycerides (TG),
      total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels
      were higher in Group A (P < 0.05). TSH and osteocalcin levels were similar in
      males with different HOMA-IR. Multiple regression analysis for TSH and
      osteocalcin showed that in Group A these hormones had no effect on plasma
      lipoproteins. However, in Group B they significantly determined the variation of
      plasma TC and low-density lipoprotein cholesterol (LDL-C) levels (in about 28%
      and 29%, respectively). We concluded that TSH and osteocalcin are involved in
      determination of a more healthy lipid profile at a certain level of insulin
      sensitivity. 

PMID- 24899779
TI  - The influence of obesity and ambient temperature on physiological and oxidative
      responses to submaximal exercise.
AB  - This study investigated the effects of obesity and ambient temperature on
      physiological responses and markers of oxidative stress to submaximal exercise in
      obese and lean people. Sixteen healthy males were divided into an obese group
      (n=8, %fat: 27.00+/-3.00%) and a lean group (n=8, %fat: 13.85+/-2.45%). Study
      variables were measured during a 60 min submaximal exercise test at 60% VO2max in
      a neutral (21+/-1 degrees C) and a cold (4+/-1 degrees C) environment. Heart
      rate, blood lactate, rectal temperature, serum levels of malondialdehyde (MDA)
      and superoxide dismutase (SOD) were measured at rest, during exercise and in
      recovery. Heart rate of both groups was significantly lower (P<0.05) in the cold
      than the warm environment, but there were no significant differences between the
      two groups. Serum SOD activity increased to a significantly greater extent
      (P<0.05) in the cold than the neutral environment, and remained elevated for
      longer during exercise in the obese group than the lean group. Serum MDA level
      during submaximal exercise was not significantly different between conditions or
      groups. Cold stress in exercise may challenge antioxidant defence mechanisms in
      obese subjects, but lipid peroxidation remains unchanged. 

PMID- 24899780
TI  - Comparison of physiological reactions and physiological strain in healthy men
      under heat stress in dry and steam heat saunas.
AB  - The aim of the paper was to follow up major physiological reactions, provoked by
      heat stress during dry and wet sauna baths. A physical strain index and
      subjective estimation of heat comfort of subjects who had not taken sauna baths
      before was also evaluated. Ten healthy males aged 25-28 underwent a dry sauna
      bath and then after a one-month break they underwent a steam sauna bath. Each
      time, they entered the sauna chamber 3 times for 15 minutes with five-minute
      breaks. During breaks they cooled their bodies with a cold shower and then rested
      in a sitting position. Before and after the baths, body mass and blood pressure
      were measured. Rectal temperature and heart rate were monitored during the baths.
      The physiological strain index (PSI) and cumulative heat strain index (CHSI) were
      calculated. Subjects assessed heat comfort by Bedford's scale. Greater body mass
      losses were observed after the dry sauna bath compared to the wet sauna (-0.72
      vs. -0.36 kg respectively). However, larger increases in rectal temperature and
      heart rate were observed during the wet sauna bath (38.8% and 21.2%
      respectively). Both types of sauna baths caused elevation of systolic blood
      pressure, but changes were greater after the dry one. Diastolic pressure was
      reduced similarly. Subjective feelings of heat comfort as well as PSI (4.83 +/-
      0.29 vs. 5.7 +/- 0.28) and CHSI (76.3 +/- 18.4 vs. 144.6 +/- 21.7) were greater
      during the wet sauna bath. It can be concluded that due to high humidity and
      reduction of thermoregulation mechanisms, the wet sauna is more stressful for the
      organism than the dry sauna, where the temperature is higher with low humidity.
      Both observed indexes (PSI and CHSI) could be appropriate for objective
      assessment of heat strain during passive heating of the organism. 

PMID- 24899782
TI  - The relationship between the number of repetitions performed at given intensities
      is different in endurance and strength trained athletes.
AB  - Prescribing training intensity and volume is a key problem when designing
      resistance training programmes. One approach is to base training prescription on
      the number of repetitions performed at a given percentage of repetition maximum
      due to the correlation found between these two measures. However, previous
      research has raised questions as to the accuracy of this method, as the
      repetitions completed at different percentages of 1RM can differ based upon the
      characteristics of the athlete. The objective of this study was therefore to
      evaluate the effect of an athlete's training background on the relationship
      between the load lifted (as a percentage of one repetition maximum) and the
      number of repetitions achieved. Eight weightlifters and eight endurance runners
      each completed a one repetition maximum test on the leg press and completed
      repetitions to fatigue at 90, 80 and 70% of their one repetition maximum. The
      endurance runners completed significantly more repetitions than the weightlifters
      at 70% (39.9 +/- 17.6 versus 17.9 +/- 2.8; p < 0.05) and 80% (19.8 +/- 6.4 versus
      11.8 +/- 2.7; p < 0.05) of their one repetition maximum but not at 90% (10.8 +/-
      3.9 versus 7.0 +/- 2.1; p > 0.05) of one repetition maximum. These differences
      could be explained by the contrasting training adaptations demanded by each
      sport. This study suggests that traditional guidelines may underestimate the
      potential number of repetitions that can be completed at a given percentage of
      1RM, particularly for endurance trained athletes. 

PMID- 24899783
TI  - A poetry program for the very elderly-Narrative perspective on one therapeutic
      model.
AB  - The focus of this report is a poetry program that the author has been conducting
      at a nursing home/short-stay rehabilitation facility for the past three and a
      half years. The program involves reading poetry to groups of very elderly
      residents who have significant mental and/or physical disabilities. This article
      includes a description of the program and the author's observations of its
      beneficial effects. Poetry readings were also given to individual seniors who
      have significant dementia. The therapeutic value of the program to the elders and
      to the person reading the poetry to the elders is discussed.

PMID- 24899781
TI  - Effect of the number of sprint repetitions on the variation of blood lactate
      concentration in repeated sprint sessions.
AB  - The aim of the present study was to examine the effect of number of sprint
      repetitions on the variation of blood lactate concentration (blood [La]) during
      different repeated-sprint sessions in order to find the appropriate number of
      sprint repetitions that properly simulates the physiological demands of team
      sport competitions. Twenty male team-sport players (age, 22.2 +/- 2.9 years)
      performed several repeated-sprint sessions (RSS) consisting of 1, 2, 3, 4, 5, 9,
      or 10 repetitions of 30 m shuttle sprints (2 * 15 m) with 30 s recovery in
      between. The blood [La] was obtained after 3 min of recovery at the end of each
      RSS. The present study showed that for RSS of 3 sprints (RSS3) there was a high
      increase (p<0.001) in blood [La], which reached approximately fivefold resting
      values (9.4+/-1.7 mmol . l(-1)) and then remained unchanged for the RSS of 4 and
      5 sprints (9.6+/-1.4 and 10.5+/-1.9 mmol . l(-1), p=0.96 and 0.26, respectively).
      After RSS9 and RSS10 blood [La] further significantly increased to 12.6 and 12.7
      mmol . l(-1), p<0.001, respectively. No significant difference was found between
      RSS3, RSS4 and RSS5 for the percentage of sprint speed decrement (Sdec) (1.5+/
      1.2; 2.0+/-1.1 and 2.6+/-1.4%, respectively). There was also no significant
      difference between RSS9 and RSS10 for Sdec (3.9+/-1.3% and 4.5+/-1.4%,
      respectively). In conclusion, the repeated-sprint protocol composed of 5 shuttle
      sprint repetitions is more representative of the blood lactate demands of the
      team sports game intensity. 

PMID- 24899784
TI  - Freestyle facial perforator flaps-a safe reconstructive option for moderate-sized
      facial defects.
AB  - BACKGROUND: Perforators are a constant anatomical finding in the facial area and
      any known flap can in theory be based on the first perforator located at the flap
      rotation axis. METHODS: A case series of single stage reconstruction of moderate
      sized facial defects using 21 perforator based local flaps in 19 patients from
      2008-2013. RESULTS: A sufficient perforator was located in every case and the
      flap rotated along its axis (76 %) or advanced (24 %). Reconstruction was
      successfully achieved with a high self reported patient satisfaction. Two minor
      complications occurred early on in the series and corrective procedures were
      performed in four patients. CONCLUSIONS: The random facial perforator flap seems
      to be a good and reliable option for the reconstruction of facial subunits,
      especially the periorbital, nasal and periocular area with a minimal morbidity
      and a pleasing result in a one stage outpatient setting. Level of Evidence: Level
      IV, therapeutic study.

PMID- 24899785
TI  - Does repeated ticking maintain tic behavior? An experimental study of eye
      blinking in healthy individuals.
AB  - Tics in Tourette syndrome (TS) are often preceded by "premonitory urges":
      annoying feelings or bodily sensations. We hypothesized that, by reducing
      annoyance of premonitory urges, tic behaviour may be reinforced. In a 2 * 2
      experimental design in healthy participants, we studied the effects of
      premonitory urges (operationalized as air puffs on the eye) and tic behaviour
      (deliberate eye blinking after a puff or a sound) on changes in subjective
      evaluation of air puffs and EMG responses on the m. orbicularis oculi. The
      experimental group with air puffs + blinking experienced a decrease in subjective
      annoyance of the air puff, but habituation of the EMG response was blocked and
      length of EMG response increased. In the control groups (air puffs without
      instruction to blink, no air puffs), these effects were absent. When
      extrapolating to the situation in TS patients, these findings suggest that
      performance of tics is reinforced by reducing the subjective annoyance of
      premonitory urges, while simultaneously preventing habituation or even inducing
      sensitisation of the physiological motor response. 

PMID- 24899786
TI  - Overexpression of interleukin-23 and interleukin-17 in the lesion of pemphigus
      vulgaris: a preliminary study.
AB  - IL-23/IL-17 axis has been identified as major factor involved in the pathogenesis
      of several autoimmune diseases; yet its pathogenetic role in pemphigus vulgaris
      (PV) remains controversial. The aim of this research was to investigate the
      potential role of IL-23/IL-17 axis in the immunopathogenesis of PV, and
      correlation between IL-23+ cells and IL-17+ cells was also evaluated. For this
      purpose, ten patients with PV, three patients with pemphigus foliaceus (PF), and
      six healthy individuals were allocated to this research. The lesional skin biopsy
      specimens were obtained before treatment. Then immunofluorescence staining was
      performed to analyze the expression of IL-23 and IL-17 in the PV/PF patients and
      the healthy individuals. The results showed that the numbers of IL-23+ and IL-17+
      cells were significantly higher in PV lesions, compared to PF lesions and normal
      control skins, respectively (all P < 0.05). Moreover, the correlation between IL
      23+ cells and IL-17+ cells was significant (r = 0.7546; P < 0.05). Taken
      together, our results provided evidence that the IL-23/IL-17 axis may play a
      crucial role in the immunopathogenesis of PV and may serve as novel therapeutic
      target for PV. 

PMID- 24899789
TI  - The contribution of occupation to health inequality.
AB  - Health is distributed unequally by occupation. Workers on a lower rung of the
      occupational ladder report worse health, have a higher probability of disability
      and die earlier than workers higher up the occupational hierarchy. Using a
      theoretical framework that unveils some of the potential mechanisms underlying
      these disparities, three core insights emerge: (i) there is selection into
      occupation on the basis of initial wealth, education, and health, (ii) there will
      be behavioural responses to adverse working conditions, which can have
      compensating or reinforcing effects on health, and (iii) workplace conditions
      increase health inequalities if workers with initially low socioeconomic status
      choose harmful occupations and don't offset detrimental health effects. We
      provide empirical illustrations of these insights using data for the Netherlands
      and assess the evidence available in the economics literature.

PMID- 24899787
TI  - Circulating Th17, Th22, and Th1 cells are elevated in the Guillain-Barre syndrome
      and downregulated by IVIg treatments.
AB  - The Guillain-Barre syndrome (GBS) is considered a T helper 1 (Th1) cells-mediated
      acute inflammatory peripheral neuropathy. However, some changes in GBS could not
      be explained completely by Th1 cells pathogenic role. Recently, Th17 cells have
      been identified and can mediate tissue inflammation and autoimmune response.
      Therefore, a study on the role of Th17 and Th22 cells and their cytokines in GBS
      is necessary for exploring the pathogenesis of GBS. Here, we detected the
      frequency of Th1, Th17, and Th22 cells by using 4-color flow cytometry and we
      detected the plasma levels of IL-17 and IL-22 by ELISA in GBS patients, relapsing
      remitting multiple sclerosis patients at the acute phase of relapse, viral
      encephalitis or meningitis patients and healthy controls. Our data showed that
      the frequency of circulating Th1, Th17, and Th22 cells was significantly
      increased in GBS patients. The plasma levels of IL-17 and IL-22 in GBS and
      relapsing-remitting multiple sclerosis at the acute phase of relapse were also
      markedly elevated. Enhanced circulating Th22 cells were correlated with GBS
      severity. Intravenous immunoglobulin therapy downregulated Th17, and Th22 cells
      and the plasma levels of IL-17 and IL-22 in GBS patients. Th17 and Th22 cells may
      be involved in the pathogenesis of GBS, and intravenous immunoglobulin mediates
      therapeutic effects by downregulating these cells and their cytokines. 

PMID- 24899790
TI  - Preparative isolation and purification of iridoid glycosides from Fructus Corni
      by high-speed countercurrent chromatography.
AB  - Using a two-phase solvent system composed of dichloromethane-methanol-n-butanol
      water-acetic acid (5:5:3:4:0.1, v/v/v/v/v), high-speed countercurrent
      chromatography was successfully performed for isolation and purification of three
      iridoid glycosides from Fructus Corni for the first time. From 100 mg of a crude
      extract of Fructus Corni 7.9 mg of sweroside, 13.1 mg of morroniside, and 10.2 mg
      of loganin were obtained in less than 3 h with purities of 92.3, 96.3 and 94.2%,
      respectively. These target compounds were identified by ESI-MS, 1H NMR and 13C
      NMR.

PMID- 24899791
TI  - HLA-DRB1*08:02 Is Associated with Bucillamine-Induced Proteinuria in Japanese
      Rheumatoid Arthritis Patients.
AB  - BACKGROUND: Drug-induced proteinuria can occur in rheumatoid arthritis (RA)
      patients treated with d-penicillamine, gold salts, or bucillamine (Buc), and
      represents a drug hypersensitivity reaction. Striking associations of human
      leukocyte antigen (HLA) alleles with adverse reactions have recently been
      reported for many drugs. METHODS: We investigated the association of HLA class II
      with Buc-induced proteinuria (BI-Pro) in 485 Japanese RA patients treated with
      Buc, of whom 25 had developed BI-Pro. RESULTS AND CONCLUSION: This preliminary
      study showed a highly significant association of DRB1*08:02 with BI-Pro (P = 1.09
      * 10(-6), corrected P [Pc] = 1.96 * 10(-5), odds ratio [OR] 25.17, 95% confidence
      interval [CI] 7.98-79.38). DQB1*04:02 was also significantly associated with
      increased risk of BI-Pro (P = 2.44 * 10(-5), Pc = 2.69 * 10(-4), OR 10.35, 95%CI
      3.99-26.83). These findings provide useful information for promoting personalized
      medicine for RA.

PMID- 24899792
TI  - Naturopathic practice at north american academic institutions: description of
      300,483 visits and comparison to conventional primary care.
AB  - This study collected patient visit data to explore similarities and differences
      between conventional and naturopathic primary care (PC). Administrative data from
      practice management software systems from the main teaching clinics of four of
      the eight accredited North American naturopathic academic institutions were
      abstracted into an integrated database containing five years (2006-2010) of
      visit, patient, laboratory, and prescribing data. Descriptive analyses of
      healthcare services were compared to the National Ambulatory Medical Care Survey
      (NAMCS). Over the five-year period, 300,483 patient visits to naturopathic
      doctors occurred at clinics, excluding visits at clinics operated by the schools
      in community settings. Patients were 69% female; mean age was 39 (SE 0.09). Older
      adults (>65) comprised 9% of the population and children (<16) comprised 8%.
      Comparing academic naturopathic clinics to national conventional PC (NAMCS), we
      found more patients paid out of pocket at naturopathic clinics (50 vs. 4%) and
      naturopathic clinics more frequently offered discounted care (26 vs. 0.3%). There
      was a 44% overlap in the most frequent 25 diagnoses for PC at conventional
      community clinics. Overall, these data suggest substantial similarities in care
      offered by academic naturopathic clinics, at which most Naturopathic Doctor (ND)
      students are trained, and by conventional PC practices. 

PMID- 24899793
TI  - Long-term visual outcomes after Crystalens((r)) HD intraocular lens implantation.
AB  - PURPOSE: Our purpose was to evaluate the long-term visual outcomes after
      bilateral implantation of Crystalens((r)) HD (Bausch and Lomb, Inc.)
      accommodative intraocular lenses. METHODS: In this study, 25 patients (50 eyes)
      who underwent cataract surgery and bilateral Crystalens HD accommodative
      intraocular lens implantation were included. The Crystalens HD lens was implanted
      in the bag in both eyes, without any intra- or postoperative complications. The
      visual parameters measured before and after surgery were: uncorrected distance
      visual acuity, corrected distance visual acuity (CDVA) (using the Early Diabetic
      Retinopathy Study [EDTRS] logMAR charts), uncorrected intermediate visual acuity,
      and uncorrected near visual acuity using a Birkhauser reading chart, at a
      distance of 66 cm and 33 cm for intermediate and near vision, respectively,
      directly illuminated by a lamp of 60 watts. After surgery, the patients were
      evaluated at 1, 3, 6, 12, 24, and 36 months. RESULTS: The mean age was 68.70+/
      7.1 (range: 54 to 83) years. The mean follow-up was 42.72+/-0.49 (range: 42.33 to
      43.27) months. The uncorrected distance visual acuity improved from 0.56+/-0.41
      (range: 0 to 2) preoperatively to 0.19+/-0.13 (range: 0 to 0.38) (logMAR scale)
      at the last follow-up visit, and the CDVA improved from 0.17+/-0.18 (range: 0 to
      0.7) preoperatively to 0.05+/-0.05 (range: -0.02 to 0.22) at the last follow-up
      visit. No eyes lost lines of CDVA during the follow-up period, while 54% of
      patients gained one or more lines of CDVA. The uncorrected intermediate and near
      visual acuity was J2 or better in 71% and 69% of our patients, respectively.
      CONCLUSION: Crystalens HD implantation seems to provide an improvement in visual
      acuity for far, intermediate, and near distances.

PMID- 24899788
TI  - Obesity, inflammation, and lung injury (OILI): the good.
AB  - Obesity becomes pandemic, predisposing these individuals to great risk for lung
      injury. In this review, we focused on the anti-inflammatories and addressed the
      following aspects: adipocytokines and obesity, inflammation and other mechanisms,
      adipocytokines and lung injury in obesity bridged by inflammation, and potential
      therapeutic targets. To sum up, the majority of evidence supported that
      adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5) were
      reduced significantly in obesity, which is associated with increased
      inflammation, indicated by increase of TNF alpha and IL-6, through activation of
      toll-like receptor (TLR4) and nuclear factor light chain kappa B (NF- kappa B)
      signaling pathways. Administration of these adipocytokines promotes weight loss
      and reduces inflammation. Zinc-alpha 2-glycoprotein (ZAG), vaspin, IL-10,
      interleukin-1 receptor antagonist (IL-1RA), transforming growth factor beta (TGF
      beta1), and growth differentiation factor 15 (GDF15) are also regarded as anti
      inflammatories. There were controversial reports. Furthermore, there is a huge
      lack of studies for obesity related lung injury. The effects of adiponectin on
      lung transplantation, asthma, chronic obstructive pulmonary diseases (COPD), and
      pneumonia were anti-inflammatory and protective in lung injury. Administration of
      IL-10 agonist reduces mortality of acute lung injury in rabbits with acute
      necrotizing pancreatitis, possibly through inhibiting proinflammation and
      strengthening host immunity. Very limited information is available for other
      adipocytokines.

PMID- 24899794
TI  - The effects of ranibizumab injections on fluorescein angiographic findings and
      visual acuity recovery in age-related macular degeneration.
AB  - AIM: The objective of the study reported here was to evaluate the effect of
      ranibizumab on retinal circulation times and vessel caliber and to analyze the
      correlation of these factors with visual acuity (VA) prognosis in patients with
      age-related macular degeneration (AMD). SUBJECTS AND METHODS: This prospective
      cohort study included 52 eyes of 46 patients (mean age 73.5 years [standard
      deviation 7.7]; 28 males, 18 females). The study parameters were best-corrected
      visual acuity (BCVA), central macular thickness (CMT) (pre- and posttreatment:
      for 3 months after the last injection), retinal circulation times, diameter of
      retinal arteriole (DRA), and diameter of retinal vein (DRV) (pre- and
      posttreatment: after a loading dose of three consecutive injections of
      ranibizumab with a 4-week interval in the initial phase). The pretreatment,
      posttreatment measurements, and their differences were recorded for analyses. The
      injections were repeated when needed. Eyes were grouped into one of two groups
      according to VA recovery: Group 1, cases showing significant recovery of VA
      (n=21, 37%), and Group 2, cases showing preservation of VA (n=22, 42%) and
      deterioration of VA (n=11, 21%). Differences were compared statistically in and
      between groups. Logistic regression analysis was undertaken to determine the
      correlation of these parameters with VA recovery. RESULTS: There was a
      significant reduction in DRA (P=0.007) and CMT levels (P<0.001) in both study
      groups after treatment. When the two groups were compared, the differences in
      pretreatment values of DRA (P=0.001), DRV (P=0.017), CMT (P=0.039), and mean BCVA
      (P=0.00) were found to be statistically significant. Posttreatment changes in DRA
      (P=0.013) and mean CMT (P=0.010) were found to be factors related to VA recovery
      by logistic regression analysis. CONCLUSION: Our findings reveal that ranibizumab
      treatment is associated with decrease in DRA, CMT, and significant improvement in
      VA recovery. Further, taking into account the cases in which VA was preserved,
      when needed, ranibizumab should be re-injected after the loading dose.

PMID- 24899795
TI  - Macular optical coherence tomography findings following blunt ocular trauma.
AB  - This case report describes the optical coherence tomography (OCT) results of
      Berlin's edema in a male subject following blunt ocular trauma from a soccer
      ball. A 27-year-old male presented with blurred vision in his left eye following
      blunt trauma. On admission, he underwent a complete eye examination and an OCT of
      the macula. Fundoscopy revealed commotio retinae, observed as an abnormal cream
      colored discoloration of the fovea. The OCT showed outer photoreceptor segment
      disruption, retinal pigment epithelium inter-digitation, and intra-retinal edema
      of the outer nuclear layer. Following initial management, a repeat OCT after 3
      months showed near complete resolution. OCT can be a useful adjunct for
      monitoring the progress of Berlin's edema secondary to blunt ocular trauma
      because Berlin's edema may present similarly clinically to other ocular trauma,
      but can affect different layers of the retina depending on the type of injury to
      the eye. 

PMID- 24899796
TI  - Retinoblastoma: experience of a referral center in the North Region of Portugal.
AB  - PURPOSE: To describe the experience of the Ophthalmology Department of Hospital
      Sao Joao (HSJ), a tertiary health care center in North Region, Portugal, in terms
      of the diagnosis, treatment, and follow-up of retinoblastoma. METHODS: This was a
      retrospective study of patients diagnosed with retinoblastoma in Hospital Sao
      Joao, between 1978 and 2012. RESULTS: Fifty patients with retinoblastoma were
      evaluated in our institution between 1978 and 2012. Four patients were excluded
      due to loss of follow-up. Among the 46 retinoblastoma cases, 33 (71.7%) were
      unilateral and 13 (28.3%) bilateral, with a mean age at diagnosis of 22.19 months
      and 6.92 months, respectively (P<0.001). Leukocoria was the most common
      presenting sign (36.9%), followed by strabismus (19.6%), a combination of
      leukocoria and strabismus (8.7%), and buphthalmia (2.2%). Between 1978 and 1992,
      nine retinoblastoma cases were referred to our hospital, all of them unilateral,
      and, in each case, enucleation was performed, with or without salvage therapy.
      Between 1993 and 2012, 18 eyes with retinoblastoma were successfully managed with
      conservative treatment. CONCLUSION: Demographic results were generally coincident
      with previous reports. It is crucial to screen leukocoria in pediatric practice,
      even in asymptomatic children. The outcome of retinoblastoma treatment in our
      hospital is similar to other series in developed countries.

PMID- 24899797
TI  - Resolution of foveal detachment in dome-shaped macula after treatment by
      spironolactone: report of two cases and mini-review of the literature.
AB  - Dome-shaped macula (DSM) was recently described in myopic patients as a convex
      protrusion of the macula within a posterior pole staphyloma. The pathogenesis of
      DSM and the development of associated serous foveal detachment (SFD) remain
      unclear. The obstruction of choroidal outflow and compressive changes of
      choroidal capillaries have been proposed as causative factors. In this paper, we
      report two cases of patients with chronic SFD associated with DSM treated with
      oral spironolactone. After treatment, there was a complete resolution of SFD in
      both patients. To the best of our knowledge, this is the first report of
      successful treatment of SFD in DSM by a mineralocorticoid receptor antagonist. 

PMID- 24899798
TI  - Visual and subjective outcomes of phototherapeutic keratectomy after Descemet's
      stripping endothelial keratoplasty.
AB  - BACKGROUND: Patients with endothelial disease also often have scarring or surface
      corneal disease. This study examined the outcomes of phototherapeutic keratectomy
      (PTK) performed in patients with prior Descemet's stripping endothelial
      keratoplasty (DSEK). METHODS: This retrospective case series examined all
      patients undergoing PTK after DSEK in a single private practice. The primary
      outcome was best-corrected visual acuity, with secondary outcomes of change in
      spherical equivalent versus targeted change, change in endothelial cell count,
      improvement in corneal topography, and subjective satisfaction with vision.
      RESULTS: For the ten patients who met the inclusion criteria, mean best-corrected
      visual acuity improved from logarithm of the minimum angle of resolution (logMAR)
      0.43 to 0.36 (P=0.24) at the most recent postoperative visit. PTK treatments that
      included a refractive component showed good predictability of 1.13 diopters
      spherical equivalent/diopter attempted. There was no evidence of a decrease in
      endothelial cell count from PTK, even with the use of mitomycin C (P=0.95).
      Subjectively, 80% of patients noted improvement in their vision. CONCLUSION: PTK
      after DSEK has the potential to improve patients' vision with high levels of
      patient satisfaction, even though many patients had significant ocular
      comorbidities. Surgeons should consider using PTK to treat anterior corneal
      pathology following DSEK.

PMID- 24899799
TI  - Optical coherence tomographic findings at the fixation point in a case of
      bilateral congenital macular coloboma.
AB  - BACKGROUND: Congenital macular coloboma is a rare ocular disease that consists of
      atrophic lesions in the macula with well-circumscribed borders. We report the
      findings of spectral domain optical coherence tomography (SD-OCT) at the fixation
      point in a case of bilateral macular coloboma. CASE REPORT: The subject is a 4
      year-old boy. He visited our hospital at age 1 year and 4 months for the
      evaluation of strabismus. The fundus examination of both eyes showed round-shaped
      sharply-demarcated atrophic lesions involving the macula with large choroidal
      vessels and bared sclera at the base. Immunologic tests including toxoplasmosis,
      rubella, varicella, herpes virus, and human T-cell leukemia virus were all
      negative. At age 4 years and 1 month, cycloplegic refraction showed insignificant
      refractive errors and his best corrected visual acuity was 0.6 bilaterally. The
      SD-OCT showed a crater-like depression accompanying atrophic neurosensory retina,
      and the absence of retinal pigment epithelium and choroid. Examination of the
      fixation behavior by visuscope showed steady fixation with an area 0.5 degrees 
      nasal to the nasal edge of the atrophic lesion bilaterally. The SD-OCT findings
      at fixation area showed remaining normal retinal structures involving inner
      segment-outer segment (IS/OS) junction line. CONCLUSION: The findings of SD-OCT
      have been shown to be useful in the diagnosis of macular coloboma. In the
      fixation point, the structure of retina and choroid were well preserved.

PMID- 24899800
TI  - Visual loss and optic nerve head swelling in thiamine deficiency without
      prolonged dietary deficiency.
AB  - Visual loss due to optic neuropathy is a rare manifestation of thiamine
      deficiency. We report a case of a 39-year-old woman with a body mass index (BMI)
      of 29 kg/m(2) who developed visual loss and bilateral optic nerve head swelling
      after a short, self-limited gastrointestinal illness. She was disoriented and
      inattentive and had absent ankle jerk reflexes, diminished sensation in both legs
      below the knees, and marked truncal ataxia. Magnetic resonance imaging (MRI)
      showed increased T2-signal in the medial thalami and mammillary bodies. The serum
      thiamine level was 8 nmol/L (normal 8-30). The diagnosis of thiamine deficiency
      was made, and the patient's vision and neurologic symptoms improved significantly
      with intramuscular thiamine treatment. Thiamine deficiency can occur in the
      absence of an obvious predisposing factor such as alcoholism or low body weight.
      The clinician must be aware of the factors that govern vitamin availability and
      maintain a high index of suspicion to make the diagnosis in such cases. 

PMID- 24899801
TI  - Pharmacoinformatics elucidation of potential drug targets against migraine to
      target ion channel protein KCNK18.
AB  - Migraine, a complex debilitating neurological disorder is strongly associated
      with potassium channel subfamily K member 18 (KCNK18). Research has emphasized
      that high levels of KCNK18 may be responsible for improper functioning of
      neurotransmitters, resulting in neurological disorders like migraine. In the
      present study, a hybrid approach of molecular docking and virtual screening were
      followed by pharmacophore identification and structure modeling. Screening was
      performed using a two-dimensional similarity search against recommended migraine
      drugs, keeping in view the physicochemical properties of drugs. LigandScout tool
      was used for exploring pharmacophore properties and designing novel molecules.
      Here, we report the screening of four novel compounds that have showed maximum
      binding affinity against KCNK18, obtained through the ZINC database, and Drug and
      Drug-Like libraries. Docking studies revealed that Asp-46, Ile-324, Ile-44, Gly
      118, Leu-338, Val-113, and Phe-41 are critical residues for receptor-ligand
      interaction. A virtual screening approach coupled with docking energies and
      druglikeness rules illustrated that ergotamine and PB-414901692 are potential
      inhibitor compounds for targeting KCNK18. We propose that selected compounds may
      be more potent than the previously listed drug analogs based on the binding
      energy values. Further analysis of these inhibitors through site-directed
      mutagenesis could be helpful for exploring the details of ligand-binding pockets.
      Overall, the findings of this study may be helpful for designing novel
      therapeutic targets to cure migraine. 

PMID- 24899802
TI  - The Purine Bias of Coding Sequences is Determined by Physicochemical Constraints
      on Proteins.
AB  - For this report, we analyzed protein secondary structures in relation to the
      statistics of three nucleotide codon positions. The purpose of this investigation
      was to find which properties of the ribosome, tRNA or protein level, could
      explain the purine bias (Rrr) as it is observed in coding DNA. We found that the
      Rrr pattern is the consequence of a regularity (the codon structure) resulting
      from physicochemical constraints on proteins and thermodynamic constraints on
      ribosomal machinery. The physicochemical constraints on proteins mainly come from
      the hydropathy and molecular weight (MW) of secondary structures as well as the
      energy cost of amino acid synthesis. These constraints appear through a network
      of statistical correlations, such as (i) the cost of amino acid synthesis, which
      is in favor of a higher level of guanine in the first codon position, (ii) the
      constructive contribution of hydropathy alternation in proteins, (iii) the
      spatial organization of secondary structure in proteins according to solvent
      accessibility, (iv) the spatial organization of secondary structure according to
      amino acid hydropathy, (v) the statistical correlation of MW with protein
      secondary structures and their overall hydropathy, (vi) the statistical
      correlation of thymine in the second codon position with hydropathy and the
      energy cost of amino acid synthesis, and (vii) the statistical correlation of
      adenine in the second codon position with amino acid complexity and the MW of
      secondary protein structures. Amino acid physicochemical properties and
      functional constraints on proteins constitute a code that is translated into a
      purine bias within the coding DNA via tRNAs. In that sense, the Rrr pattern
      within coding DNA is the effect of information transfer on nucleotide composition
      from protein to DNA by selection according to the codon positions. Thus, coding
      DNA structure and ribosomal machinery co-evolved to minimize the energy cost of
      protein coding given the functional constraints on proteins. 

PMID- 24899803
TI  - Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using
      synchrotron-based monoenergetic photon beams.
AB  - Gold nanoparticles have been shown to enhance radiation doses delivered to
      biological targets due to the high absorption coefficient of gold atoms, stemming
      from their high atomic number (Z) and physical density. These properties
      significantly increase the likelihood of photoelectric effects and Compton
      scattering interactions. Gold nanoparticles are a novel radiosensitizing agent
      that can potentially be used to increase the effectiveness of current radiation
      therapy techniques and improve the diagnosis and treatment of cancer. However,
      the optimum radiosensitization effect of gold nanoparticles is strongly dependent
      on photon energy, which theoretically is predicted to occur in the kilovoltage
      range of energy. In this research, synchrotron-generated monoenergetic X-rays in
      the 30-100 keV range were used to investigate the energy dependence of
      radiosensitization by gold nanoparticles and also to determine the photon energy
      that produces optimum effects. This investigation was conducted using cells in
      culture to measure dose enhancement. Bovine aortic endothelial cells with and
      without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50,
      60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after
      irradiation to determine cell viability. Cell radiosensitivity enhancement was
      indicated by the dose enhancement factor which was found to be maximum at 40 keV
      with a value of 3.47. The dose enhancement factor obtained at other energy levels
      followed the same direction as the theoretical calculations based on the ratio of
      the mass energy absorption coefficients of gold and water. This experimental
      evidence shows that the radiosensitization effect of gold nanoparticles varies
      with photon energy as predicted from theoretical calculations. However,
      prediction based on theoretical assumptions is sometimes difficult due to the
      complexity of biological systems, so further study at the cellular level is
      required to fully characterize the effects of gold nanoparticles with ionizing
      radiation. 

PMID- 24899804
TI  - Silver nanoparticles promote osteogenic differentiation of human urine-derived
      stem cells at noncytotoxic concentrations.
AB  - In tissue engineering, urine-derived stem cells are ideal seed cells and silver
      nanoparticles (AgNPs) are perfect antimicrobial agents. Due to a distinct lack of
      information on the effects of AgNPs on urine-derived stem cells, a study was
      conducted to evaluate the effects of silver ions and AgNPs upon the cytotoxicity
      and osteogenic differentiation of urine-derived stem cells. Initially, AgNPs or
      AgNO3 were exposed to urine-derived stem cells for 24 hours. Cytotoxicity was
      measured using the Cell Counting kit-8 (CCK-8) test. The effects of AgNPs or
      AgNO3 at the maximum safety concentration determined by the CCK-8 test on
      osteogenic differentiation of urine-derived stem cells were assessed by alkaline
      phosphatase activity, Alizarin Red S staining, and the quantitative reverse
      transcription polymerase chain reaction. Lastly, the effects of AgNPs or AgNO3 on
      "urine-derived stem cell actin cytoskeleton organization" and RhoA activity were
      assessed by rhodamine-phalloidin staining and Western blotting. Concentration
      dependent toxicity was observed starting at an AgNO3 concentration of 2 MUg/mL
      and at an AgNP concentration of 4 MUg/mL. At these concentrations, AgNPs were
      observed to promote osteogenic differentiation of urine-derived stem cells,
      induce actin polymerization and increase cytoskeletal tension, and activate RhoA;
      AgNO3 had no such effects. In conclusion, AgNPs can promote osteogenic
      differentiation of urine-derived stem cells at a suitable concentration,
      independently of silver ions, and are suitable for incorporation into tissue
      engineered scaffolds that utilize urine-derived stem cells as seed cells. 

PMID- 24899805
TI  - Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed
      aqueous extract.
AB  - Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal
      nanoparticles for multiple applications across a broad spectrum in the biomedical
      field, including the diagnosis and treatment of cancer. In previous work, we
      synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient,
      one-step green method involving reduction of ferric chloride solution using brown
      seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and
      amino functional groups mainly relevant to polysaccharides, which acts as a
      potential stabilizer and metal reductant agent. The aim of this study was to
      evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4
      MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for
      leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa
      cells), and liver cancer (HepG2 cells). The cancer cells were treated with
      different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]
      2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity,
      resulting in an inhibitory concentration 50 (IC50) value of 23.83+/-1.1 MUg/mL
      (HepG2), 18.75+/-2.1 MUg/mL (MCF-7), 12.5+/-1.7 MUg/mL (HeLa), and 6.4+/-2.3
      MUg/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected
      for further investigation. The representative dot plots from flow cytometric
      analysis of apoptosis showed that the percentages of cells in early apoptosis and
      late apoptosis were increased. Cell cycle analysis showed a significant increase
      in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction
      of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9
      in a time-response fashion. The nature of the biosynthesis and therapeutic
      potential of Fe3O4 MNPs could pave the way for further research on the green
      synthesis of therapeutic agents, particularly in nanomedicine, to assist in the
      treatment of cancer. 

PMID- 24899806
TI  - Latent class analysis on internet and smartphone addiction in college students.
AB  - PURPOSE: This study aimed to classify distinct subgroups of people who use both
      smartphone and the internet based on addiction severity levels. Additionally, how
      the classified groups differed in terms of sex and psychosocial traits was
      examined. METHODS: A total of 448 university students (178 males and 270 females)
      in Korea participated. The participants were given a set of questionnaires
      examining the severity of their internet and smartphone addictions, their mood,
      their anxiety, and their personality. Latent class analysis and ANOVA (analysis
      of variance) were the statistical methods used. RESULTS: Significant differences
      between males and females were found for most of the variables (all <0.05).
      Specifically, in terms of internet usage, males were more addicted than females
      (P<0.05); however, regarding smartphone, this pattern was reversed (P<0.001). Due
      to these observed differences, classifications of the subjects into subgroups
      based on internet and smartphone addiction were performed separately for each
      sex. Each sex showed clear patterns with the three-class model based on
      likelihood level of internet and smartphone addiction (P<0.001). A common trend
      for psychosocial trait factors was found for both sexes: anxiety levels and
      neurotic personality traits increased with addiction severity levels (all
      P<0.001). However, Lie dimension was inversely related to the addiction severity
      levels (all P<0.01). CONCLUSION: Through the latent classification process, this
      study identified three distinct internet and smartphone user groups in each sex.
      Moreover, psychosocial traits that differed in terms of addiction severity levels
      were also examined. It is expected that these results should aid the
      understanding of traits of internet and smartphone addiction and facilitate
      further study in this field.

PMID- 24899807
TI  - Psychometric evaluation of the Sheehan Disability Scale in adult patients with
      attention-deficit/hyperactivity disorder.
AB  - Inattention and impulsivity symptoms are common among adults with attention
      deficit/hyperactivity disorder (ADHD), which can lead to difficulty
      concentrating, restlessness, difficulty completing tasks, disorganization,
      impatience, and impulsiveness. Many adults with ADHD find it difficult to focus
      and prioritize. Resulting outcomes, such as missed deadlines and forgotten
      engagements, may ultimately impact the ability to function at work, school, home,
      or in a social environment. The European Medicines Agency guidelines for
      evaluating medicinal products for ADHD recommend inclusion of both functional
      outcomes, such as school, social, or work functioning, and outcomes related to
      symptoms of ADHD in clinical studies of novel medication primary efficacy
      endpoints. Due to its performance in other disease areas and the relevance of its
      items as evidenced by content validity analyses, the Sheehan Disability Scale
      (SDS) was chosen to assess functional impairment in ADHD. The aim of this study
      was to investigate the psychometric properties of the SDS, used as a brief
      measure of functional impairment in a number of psychiatric disorders, in adult
      patients with ADHD. To the authors' knowledge, this is the first study to
      evaluate the reliability of the SDS (based on Cronbach's coefficient alpha and
      test-retest reliability), its validity (construct and known-groups validity), and
      its ability to detect change in this patient population. This study also
      established a preliminary responder definition for the SDS in this study
      population to determine when change can be considered clinically beneficial in a
      clinical trial setting. The psychometric results support the use of the SDS
      subscales (items 1-3) and total score (sum of items 1-3) in an ADHD population.
      In addition, the evaluation provides evidence for a three-point preliminary
      responder definition for the SDS and further evidence of its responsiveness in
      adults with ADHD. Altogether, the results indicate that the SDS is a simple and
      easy-to-score scale that would have great utility in future clinical trials for
      monitoring functional impairment in adults with ADHD. 

PMID- 24899808
TI  - Neuropathic sensory symptoms: association with pain and psychological factors.
AB  - BACKGROUND: A large number of population-based studies of chronic pain have
      considered neuropathic sensory symptoms to be associated with a high level of
      pain intensity and negative affectivity. The present study examines the question
      of whether this association previously found in non-selected samples of chronic
      pain patients can also be found in chronic pain patients with underlying
      pathology of neuropathic sensory symptoms. METHODS: Neuropathic sensory symptoms
      in 306 patients with chronic pain diagnosed as typical neuropathic pain,
      radiculopathy, fibromyalgia, or nociceptive back pain were assessed using the
      Pain DETECT Questionnaire. Two separate cluster analyses were performed to
      identify subgroups of patients with different levels of self-reported neuropathic
      sensory symptoms and, furthermore, to identify subgroups of patients with
      distinct patterns of neuropathic sensory symptoms (adjusted for individual
      response bias regarding specific symptoms). RESULTS: ANOVA (analysis of variance)
      results in typical neuropathic pain, radiculopathy, and fibromyalgia showed no
      significant differences between the three levels of neuropathic sensory symptoms
      regarding pain intensity, pain chronicity, pain catastrophizing, pain acceptance,
      and depressive symptoms. However, in nociceptive back pain patients, significant
      differences were found for all variables except pain chronicity. When controlling
      for the response bias of patients in ratings of symptoms, none of the patterns of
      neuropathic sensory symptoms were associated with pain and psychological factors.
      CONCLUSION: Neuropathic sensory symptoms are not closely associated with higher
      levels of pain intensity and cognitive-emotional evaluations in chronic pain
      patients with underlying pathology of neuropathic sensory symptoms. The findings
      are discussed in term of differential response bias in patients with versus
      without verified neuropathic sensory symptoms by clinical examination, medical
      tests, or underlying pathology of disease. Our results lend support to the
      importance of using adjusted scores, thereby eliminating the response bias, when
      investigating self-reported neuropathic symptoms by patients.

PMID- 24899810
TI  - Social support networks and eating disorders: an integrative review of the
      literature.
AB  - AIMS: This study aimed to analyze the scientific literature about social networks
      and social support in eating disorders (ED). METHODS: By combining keywords, an
      integrative review was performed. It included publications from 2006-2013,
      retrieved from the MEDLINE, LILACS, PsycINFO, and CINAHL databases. The selection
      of articles was based on preestablished inclusion and exclusion criteria.
      RESULTS: A total of 24 articles were selected for data extraction. There was a
      predominance of studies that used nonexperimental and descriptive designs, and
      which were published in international journals. This review provided evidence of
      the fact that fully consolidated literature regarding social support and social
      networks in patients with ED is not available, given the small number of studies
      dedicated to the subject. We identified evidence that the family social network
      of patients with ED has been widely explored by the literature, although there is
      a lack of studies about other networks and sources of social support outside the
      family. CONCLUSION: The evidence presented in this study shows the need to
      include other social networks in health care. This expansion beyond family
      networks would include significant others - such as friends, colleagues,
      neighbors, people from religious groups, among others - who could help the
      individual coping with the disorder. The study also highlights the need for
      future research on this topic, as well as a need for greater investment in
      publications on the various dimensions of social support and social networks.

PMID- 24899809
TI  - Electroretinographic modifications induced by agomelatine: a novel avenue to the
      understanding of the claimed antidepressant effect of the drug?
AB  - BACKGROUND: Agomelatine, the first melatonergic antidepressant, has been
      postulated to enhance the dopaminergic activity at the central nervous system by
      5-hydroxytryptamine receptor type 2C (5-HT2C) antagonism, yet the impact of
      melatonergic agonism on this pathway is unclear. Previous studies employing
      simplified, yet reliable, proxy (retinal) measures of the central nervous system
      dopaminergic activity, namely the standard electroretinogram (ERG) technique,
      suggested a reduction of the dopaminergic activity of the main ERG parameter, the
      b-wave, by pure melatonin, notably a hormone devoid of any antidepressant
      activity. Therefore, the antidepressant effects of the melatonergic
      antidepressant drug agomelatine should be reflected by a differential b-wave
      trend at ERG versus the effect exerted by pure melatonin, which was eventually
      found to be due to a contrasting effect on central dopaminergic transmission
      between the two drugs. OBJECTIVE AND METHODS: The aim of the present preliminary
      ERG study carried out on healthy volunteers (n=23) receiving agomelatine was to
      explore the impact of this antidepressant drug on b-wave amplitude and latency of
      cones in daylight conditions using standard ERG. RESULTS: As postulated,
      agomelatine induced an enhancement of retinal dopaminergic activity, in contrast
      to what has been previously documented for melatonin. CONCLUSION: Given the
      limits of this explorative study, especially the lack of a control group and that
      of a luminance response function to measure retinal sensitivity, further studies
      in clinical samples are recommended to allow more tenable conclusions about the
      potential role of ERG in discriminating between 5-HT antagonism and melatonergic
      (MT) agonism in relationship to the claimed antidepressant effect of agomelatine.

PMID- 24899811
TI  - Possible association between vitamin D deficiency and restless legs syndrome.
AB  - BACKGROUND AND AIM: Restless legs syndrome (RLS) is a distressing sleep disorder
      that occurs worldwide. Although there have been recent developments in
      understanding the pathophysiology of RLS, the exact mechanism of the disease has
      not been well elucidated. An increased prevalence of neurologic and psychiatric
      diseases involving dopaminergic dysfunction in vitamin D-deficient patients led
      us to hypothesize that vitamin D deficiency might result in dopaminergic
      dysfunction and consequently, the development of RLS (in which dopaminergic
      dysfunction plays a pivotal role). Thus, the aim of this study was to evaluate
      the relationship between vitamin D deficiency and RLS. METHODS: One hundred and
      fifty-five consecutive patients, 18-65 years of age, who were admitted to the
      Department of Internal Medicine with musculoskeletal symptoms and who
      subsequently underwent neurological and electromyography (EMG) examination by the
      same senior neurologist, were included in this study. The patients were divided
      into two groups according to serum 25-hydroxyvitamin D (25(OH)D) (a vitamin D
      metabolite used as a measure of vitamin D status) level: 36 patients with serum
      25(OH)D levels >=20 ng/mL comprised the normal vitamin D group, and 119 patients
      with serum 25(OH)D levels <20 ng/mL comprised the vitamin D deficiency group. The
      two groups were compared for the presence of RLS and associated factors. RESULTS:
      The two groups were similar in terms of mean age, sex, mean body mass index
      (BMI), and serum levels of calcium, phosphate, alkaline phosphatase (ALP), and
      ferritin. The presence of RLS was significantly higher in the vitamin D
      deficiency group (chi (2)=12.87, P<0.001). Regression analysis showed vitamin D
      deficiency and serum 25(OH)D level to be significantly associated with the
      presence of RLS (odds ratio [OR] 5.085, P<0.001 and OR 1.047, P=0.006,
      respectively). CONCLUSION: The present study demonstrated a possible association
      between vitamin D deficiency and RLS. Given the dopaminergic effects of vitamin
      D, 25(OH)D depletion may lead to dopaminergic dysfunction and may have a place in
      the etiology of RLS. Prospective vitamin D treatment studies are needed to
      confirm this relationship and to evaluate the efficacy of vitamin D as a
      treatment for RLS patients.

PMID- 24899812
TI  - Hyperactivated Signaling Pathways of Chemokine RANTES/CCL5 in Osteopathies of
      Jawbone in Breast Cancer Patients-Case Report and Research.
AB  - BACKGROUND: Hollow spaces in the jawbone have been defined as fatty degenerative
      osteonecrosis of jawbone (FDOJ) and have been linked with a dysregulated immune
      system. Little is known about the underlying relationship. OBJECTIVES: Samples of
      FDOJ were analyzed to assess expression of cytokines which can play a role in the
      pathogenesis of breast cancer (MaCa). MATERIAL AND METHODS: Samples of FDOJ
      extracted from 23 patients with MaCa and 19 healthy control jawbone samples were
      analyzed for 7 immune messengers. RESULTS: RANTES was found to be highly
      overexpressed in disease samples. No change was observed in expression levels of
      the other immune mediators. DISCUSSION: This data provides a compelling
      confirmation that FDOJ produces high levels of RANTES, a cytokine implicated in
      MaCa and metastasis. Levels detected in FDOJ are five-fold higher than that
      previously reported for MaCa tissue suggesting its role as a cytokine source in
      MaCa. CONCLUSION: We thus hypothesize that FDOJ may serve as an expeditor of MaCa
      progression, through RANTES production.

PMID- 24899813
TI  - Nutrition in medical education: reflections from an initiative at the University
      of Cambridge.
AB  - Landmark reports have confirmed that it is within the core responsibilities of
      doctors to address nutrition in patient care. There are ongoing concerns that
      doctors receive insufficient nutrition education during medical training. This
      paper provides an overview of a medical nutrition education initiative at the
      University of Cambridge, School of Clinical Medicine, including 1) the approach
      to medical nutrition education, 2) evaluation of the medical nutrition education
      initiative, and 3) areas identified for future improvement. The initiative
      utilizes a vertical, spiral approach during the clinically focused years of the
      Cambridge undergraduate and graduate medical degrees. It is facilitated by the
      Nutrition Education Review Group, a group associated with the UK Need for
      Nutrition Education/Innovation Programme, and informed by the experiences of
      their previous nutrition education interventions. Three factors were identified
      as contributing to the success of the nutrition education initiative including
      the leadership and advocacy skills of the nutrition academic team, the variety of
      teaching modes, and the multidisciplinary approach to teaching. Opportunities for
      continuing improvement to the medical nutrition education initiative included a
      review of evaluation tools, inclusion of nutrition in assessment items, and
      further alignment of the Cambridge curriculum with the recommended UK medical
      nutrition education curriculum. This paper is intended to inform other
      institutions in ongoing efforts in medical nutrition education. 

PMID- 24899814
TI  - Tryptophan and kynurenic Acid may produce an amplified effect in central fatigue
      induced by chronic sleep disorder.
AB  - Tryptophan (TRP) and its neuroactive metabolite, kynurenic acid (KYNA), are
      thought to play key roles in central fatigue, but the specifics are still
      unknown. To clarify their roles in the brain, we developed a rat model of central
      fatigue induced by chronic sleep disorder (CFSD) by disturbing the sleep-wake
      cycle. Results showed that while 5-hydroxytryptamine (5-HT) concentration did not
      differ between control and CFSD groups, levels of TRP and KYNA in the CFSD group
      were about 2 and 5 times higher in the hypothalamus, and 2 and 3.5 times higher
      in the hippocampus, respectively. Moreover, CFSD-induced fatigue led to abnormal
      running performance (via treadmill test) and social interaction (via social
      interaction test). These results support a TRP-KYNA hypothesis in central fatigue
      in which increased TRP concentration in the brain and subsequently synthesized
      KYNA may produce an amplified effect on central fatigue, with enhanced
      concentrations being a possible mechanism by which social-interaction deficits
      are generated. 

PMID- 24899815
TI  - Manumycin induces apoptosis in prostate cancer cells.
AB  - BACKGROUND: Manumycin exhibits an antitumor effect in a variety of cancer cell
      lines, including prostate cancer cell lines (DU145 and PC-3). Our previous
      studies demonstrated that manumycin induced the apoptosis of anaplastic thyroid
      cancer cells and leukemia cells via the intrinsic apoptosis pathway. In the
      current study, we further evaluated the effect of manumycin in two prostate
      cancer cell lines (LNCaP and 22Rv1), and here we elucidate some of the underlying
      mechanisms. MATERIALS AND METHODS: The cell viability of prostate cancer cells
      was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay after treatment with manumycin for 48 hours. Apoptosis was detected by flow
      cytometry using annexin V and propidium iodide. The expressions of B-cell
      lymphoma (Bcl)-2 family members and the activations of caspase-9 and caspase-3
      were detected by Western blotting. RESULTS: Manumycin treatment resulted in
      significant decreases in the viabilities of the two prostate cancer cell lines in
      a dose-dependent manner through apoptosis, and this apoptosis involved caspase-9
      activation. A specific inhibitor of caspase-9 protected cells from caspase-3
      activation, apoptosis, and cytotoxicity induced by manumycin. We also found that
      manumycin downregulated Bcl-2 expression and upregulated Bax expression.
      CONCLUSION: Our data suggest that manumycin induces apoptosis in prostate cancer
      cells through regulation of the Bcl-2 family involving caspase-9 activation.
      These results suggest that manumycin may be beneficial for the treatment of
      prostate cancer.

PMID- 24899816
TI  - Preparation and functional studies of hydroxyethyl chitosan nanoparticles loaded
      with anti-human death receptor 5 single-chain antibody.
AB  - OBJECTIVE: To prepare hydroxyethyl chitosan nanoparticles loaded with anti-human
      death receptor 5 single-chain antibody, and study their characteristics,
      functions, and mechanisms of action. MATERIALS AND METHODS: The anti-human death
      receptor 5 single-chain antibody was constructed and expressed. Protein-loaded
      hydroxyethyl chitosan nanoparticles were prepared, and their size, morphology,
      particle-size distribution and surface zeta potential were measured by scanning
      electron microscopy and laser particle-size analysis. Mouse H22 hepatocellular
      carcinoma cells were cultured, and growth inhibition was examined using the
      CellTiter-Blue cell-viability assay. Flow cytometry and Hoechst 33342 were
      employed to measure cell apoptosis. Kunming mice with H22 tumor models were
      treated with protein-loaded hydroxyethyl chitosan nanoparticles, and their body
      weight and tumor size were measured, while hematoxylin and eosin staining was
      used to detect antitumor effects in vivo and side effects from tumors. RESULTS:
      The protein-loaded hydroxyethyl chitosan nanoparticles had good stability; the
      zeta potential was -24.2+/-0.205, and the dispersion index was 0.203. The
      inhibition of the protein-loaded hydroxyethyl chitosan nanoparticles on H22
      growth was both time- and dose-dependent. Increased expressions of active caspase
      8, active caspase 3, and BAX were detected following treatment. The average
      weight gain, tumor weight, and mean tumor volume of the protein and protein
      loaded hydroxyethyl chitosan nanoparticle groups were significantly different
      (P<0.05) compared with the phosphate-buffered saline group. CONCLUSION: The
      protein-loaded hydroxyethyl chitosan nanoparticles effectively suppressed tumor
      growth, indicating that nanotechnology has the potential for broad application in
      cancer therapy.

PMID- 24899817
TI  - Corticosteroids in the treatment of dengue shock syndrome.
AB  - Dengue infection causes significant morbidity and mortality in over 100 countries
      worldwide, and its incidence is on the rise. The pathophysiological basis for the
      development of severe dengue, characterized by plasma leakage and the "shock
      syndrome" are poorly understood. No specific treatment or vaccine is available,
      and careful monitoring and judicious administration of fluids forms the mainstay
      of management at present. It is postulated that vascular endothelial dysfunction,
      induced by cytokine and chemical mediators, is an important mechanism of plasma
      leakage. Although corticosteroids are potent modulators of the immune system,
      their role in pharmacological doses in modulating the purported immunological
      effects that take place in severe dengue has been a subject of controversy. The
      key evidence related to the role of corticosteroids for various manifestations of
      dengue are reviewed here. In summary, there is currently no high-quality evidence
      supporting the beneficial effects of corticosteroids for treatment of shock,
      prevention of serious complications, or increasing platelet counts. Non
      randomized trials of corticosteroids given as rescue medication for severe shock
      have shown possible benefit. Nonetheless, the evidence base is small, and good
      quality trials are lacking. We reiterate the need for well-designed and
      adequately powered randomized controlled trials of corticosteroids for the
      treatment of dengue shock. 

PMID- 24899819
TI  - Is there a role for vedolizumab in the treatment of ulcerative colitis and
      Crohn's disease?
AB  - Inflammatory bowel disease (IBD) is an important cause of morbidity and mortality
      for millions of patients worldwide. Current treatment options include
      corticosteroids, 5-aminosalicylates, immunosuppressants, and TNFalpha
      antagonists. However, these are frequently ineffective in achieving sustained
      response and remission over time. At present, gastroenterologists lack safe and
      effective treatments if patients fail anti-TNF therapy. Vedolizumab is a
      promising new agent for IBD patients refractory to anti-TNF therapy. Vedolizumab
      is an integrin antagonist which is thought to act by reducing inflammation by
      selectively inhibiting leukocyte migration in the gut. Emerging evidence from
      clinical trials suggests a potential role for vedolizumab in both ulcerative
      colitis (UC) and Crohn's disease (CD), particularly in patients who have
      previously failed biological therapy. The safety profile of vedolizumab appears
      reasonable, possibly because it has a "gut-selective" mode of action, with no
      reported cases of progressive multifocal leukoencephalopathy, a condition which
      has been linked to another integrin antagonist, natalizumab. This review
      discusses the available evidence for integrin antagonists and their potential
      role in the management of IBD. 

PMID- 24899820
TI  - Reduction of costs for anemia-management drugs associated with the use of ferric
      citrate.
AB  - BACKGROUND: Ferric citrate is a novel phosphate binder which has the potential to
      reduce usage of erythropoietin-stimulating agents (ESAs) and intravenous (IV)
      iron used for anemia management during hemodialysis (HD) among patients with end
      stage renal disease (ESRD). Currently, the potential health care cost savings on
      a national scale due to the use of ferric citrate in ESRD are undetermined.
      METHODS: Per-patient-per-year costs of ESAs (Epogen((r)) and Aranesp((r)) [Amgen
      Inc., CA, USA]) and IV iron (Venofer((r)) [American Regent, Inc., NY, USA] and
      Ferrlecit((r)) [Sanofi US, Bridgewater, NJ, USA]) were based on RED BOOKTM
      (Truven Health Analytics New York, NY, USA) costs combined with the Centers for
      Medicare and Medicaid Services (CMS) base rate and actual usage in 2011 for the
      four drugs. The annual number of outpatients undergoing HD in the US was based on
      frequencies reported by the USRDS (United States Renal Data System). Monte Carlo
      uncertainty analysis was performed to determine total annual costs and cost
      reduction based on ferric citrate usage. RESULTS: Total annual cost of ESAs and
      IV iron for anemia management in ESRD determined by Monte Carlo analysis assuming
      CMS base rate value was 5.127 (3.664-6.260) billion USD. For actual utilization
      in 2011, total annual cost of ESAs and IV iron was 3.981 (2.780-4.930) billion
      USD. If ferric citrate usage reduced ESA utilization by 20% and IV iron by 40%,
      then total cost would be reduced by 21.2% to 4.038 (2.868-4.914) billion USD for
      the CMS base rate, and by 21.8% to 3.111 (2.148-3.845) billion USD, based on 2011
      actual utilization. CONCLUSION: It is likely that US health care costs for anemia
      management drugs associated with ESRD among HD patients can be reduced by using
      ferric citrate as a phosphate binder.

PMID- 24899822
TI  - Community-acquired pneumonia caused by carbapenem-resistant Streptococcus
      pneumoniae: re-examining its prevention and treatment.
AB  - A 73-year-old man with no significant past medical history or any history of
      health care visits was hospitalized for pneumonia. Sputum culture revealed
      multidrug-resistant Streptococcus pneumoniae, even to carbapenems. The patient
      was later treated successfully with levofloxacin. Throat cultures from his two
      grandchildren revealed S. pneumoniae with the same susceptibility pattern.
      Analysis for resistant genes revealed gPRSP (pbp1a + pbp2x + pbp2b gene variants)
      in both the patient and his grandchildren, none of whom had received pneumococcal
      vaccines of any kind. This case illustrates the importance of the emergence of
      carbapenem-resistant S. pneumoniae. Non-rational use of carbapenems for community
      acquired infections may be counterproductive. This case also highlights the
      importance of pneumococcal vaccinations in children and the elderly. 

PMID- 24899818
TI  - Current evidence and applications of photodynamic therapy in dermatology.
AB  - In photodynamic therapy (PDT) a photosensitizer - a molecule that is activated by
      light - is administered and exposed to a light source. This leads both to
      destruction of cells targeted by the particular type of photosensitizer, and
      immunomodulation. Given the ease with which photosensitizers and light can be
      delivered to the skin, it should come as no surprise that PDT is an increasingly
      utilized therapeutic in dermatology. PDT is used commonly to treat precancerous
      cells, sun-damaged skin, and acne. It has reportedly also been used to treat
      other conditions including inflammatory disorders and cutaneous infections. This
      review discusses the principles behind how PDT is used in dermatology, as well as
      evidence for current applications of PDT. 

PMID- 24899821
TI  - Inotropes do not increase mortality in advanced heart failure.
AB  - Inotrope use is one of the most controversial topics in the management of heart
      failure. While the heart failure community utilizes them and recognizes the state
      of inotrope dependency, retrospective analyses and registry data have
      overwhelmingly suggested high mortality, which is logically to be expected given
      the advanced disease states of those requiring their use. Currently, there is a
      relative paucity of randomized control trials due to the ethical dilemma of
      creating control groups by withholding inotropes from patients who require them.
      Nonetheless, results of such trials have been mixed. Many were also performed
      with agents no longer in use, on patients without an indication for inotropes, or
      at a time before automatic cardio-defibrillators were recommended for primary
      prevention. Thus, their results may not be generalizable to current clinical
      practice. In this review, we discuss current indications for inotrope use,
      specifically dobutamine and milrinone, depicting their mechanisms of action,
      delineating their patterns of use in clinical practice, defining the state of
      inotrope dependency, and ultimately examining the literature to ascertain whether
      evidence is sufficient to support the current view that these agents increase
      mortality in patients with heart failure. Our conclusion is that the evidence is
      insufficient to link inotropes and increased mortality in low output heart
      failure. 

PMID- 24899823
TI  - Cingulate metabolites during pain and morphine treatment as assessed by magnetic
      resonance spectroscopy.
AB  - BACKGROUND: Experimental investigation of cerebral mechanisms underlying pain and
      analgesia are important in the development of methods for diagnosis and treatment
      of pain. The aim of the current study was to explore brain metabolites in
      response to pain and treatment with morphine. METHODS: Proton magnetic resonance
      spectroscopy of the anterior cingulate cortex was performed in 20 healthy
      volunteers (13 males and seven females, aged 24.9+/-2.6 years) during rest and
      acute pain before and during treatment with 30 mg of oral morphine or placebo in
      a randomized, double-blinded, cross-over study design. Pain was evoked by skin
      stimulation applied to the right upper leg using a contact heat-evoked potential
      stimulator. RESULTS: Data from 12 subjects were valid for analysis. Painful
      stimulation induced an increase in N-acetylaspartate/creatine compared with rest
      (F=5.5, P=0.04). During treatment with morphine, painful stimulation induced
      decreased glutamate/creatine (F=7.3, P=0.02), myo-inositol/creatine (F=8.38,
      P=0.02), and N-acetylaspartate/creatine (F=13.8, P=0.004) concentrations, whereas
      an increase in the pain-evoked N-acetylaspartate/creatine concentration (F=6.1,
      P=0.04) was seen during treatment with placebo. CONCLUSION: This explorative
      study indicates that neuronal metabolites in the anterior cingulate cortex, such
      as N-acetylaspartate, glutamate, and myo-inositol, could be related to the
      physiology of pain and treatment with morphine. This experimental method has the
      potential to enable the study of brain metabolites involved in pain and its
      treatment, and may in the future be used to provide further insight into these
      mechanisms.

PMID- 24899825
TI  - Osteoarthritis in young, active, and athletic individuals.
AB  - Osteoarthritis (OA) is one of the most devastating chronic conditions that affect
      people around the world. Although the usual population associated with the
      condition is the elderly, who are mostly inactive, athletes and younger
      individuals are also susceptible. Depending on the population, the etiology may
      differ; injuries, occupational activities, and obesity appear to be the most
      common causes of OA in young and athletic populations. Diagnosing OA in athletes
      and young individuals is sometimes challenging because of their increased pain
      tolerance. However, the treatment of OA in these populations does not differ from
      its management in the general population. Several considerations need to be taken
      into account when choosing a treatment modality. The purpose of this review is to
      address OA in athletes and younger individuals and to discuss its presentation,
      diagnosis, and treatment. 

PMID- 24899824
TI  - Targeting GPVI as a novel antithrombotic strategy.
AB  - While platelet activation is essential to maintain blood vessel patency and
      minimize loss of blood upon injury, untimely or excessive activity can lead to
      unwanted platelet activation and aggregation. Resultant thrombosis has the
      potential to block blood vessels, causing myocardial infarction or stroke. To
      tackle this major cause of mortality, clinical therapies that target platelet
      responsiveness (antiplatelet therapy) can successfully reduce cardiovascular
      events, especially in people at higher risk; however, all current antiplatelet
      therapies carry an increased probability of bleeding. This review will evaluate
      new and emerging targets for antithrombotics, focusing particularly on platelet
      glycoprotein VI, as blockade or depletion of this platelet-specific receptor
      conveys benefits in experimental models of thrombosis and thromboinflammation
      without causing major bleeding complications. 

PMID- 24899826
TI  - Effects of oral amino Acid supplements on functional capacity in patients with
      chronic heart failure.
AB  - Amino acids (AAs) availability is reduced in patients with heart failure (HF)
      leading to abnormalities in cardiac and skeletal muscle metabolism, and
      eventually to a reduction in functional capacity and quality of life. In this
      study, we investigate the effects of oral supplementation with essential and semi
      essential AAs for three months in patients with stable chronic HF. The primary
      endpoints were the effects of AA's supplementation on exercise tolerance
      (evaluated by cardiopulmonary stress test and six minutes walking test (6MWT)),
      whether the secondary endpoints were change in quality of life (evaluated by
      Minnesota Living with Heart Failure Questionnaire-MLHFQ) and N-terminal pro-brain
      natriuretic peptide (NT-proBNP) levels. We enrolled 13 patients with chronic
      stable HF on optimal therapy, symptomatic in New York Heart Association (NYHA)
      class II/III, with an ejection fraction (EF) <45%. The mean age was 59 +/- 14
      years, and 11 (84.6%) patients were male. After three months, peak VO2 (baseline
      14.8 +/- 3.9 mL/minute/kg vs follow-up 16.8 +/- 5.1 mL/minute/kg; P = 0.008) and
      VO2 at anaerobic threshold improved significantly (baseline 9.0 +/- 3.8
      mL/minute/kg vs follow-up 12.4 +/- 3.9 mL/minute/kg; P = 0.002), as the 6MWT
      distance (baseline 439.1 +/- 64.3 m vs follow-up 474.2 +/- 89.0 m; P = 0.006).
      However, the quality of life did not change significantly (baseline 21 +/- 14 vs
      follow-up 25 +/- 13; P = 0.321). A non-significant trend in the reduction of NT
      proBNP levels was observed (baseline 1502 +/- 1900 ng/L vs follow-up 1040 +/-
      1345 ng/L; P = 0.052). AAs treatment resulted safe and was well tolerated by all
      patients. In our study, AAs supplementation in patients with chronic HF improved
      exercise tolerance but did not change quality of life. 

PMID- 24899828
TI  - A geographic distribution database of Mononychellus mites (Acari, Tetranychidae)
      on cassava (Manihot esculenta).
AB  - The genus Mononychellus is represented by 28 herbivorous mites. Some of them are
      notorious pests of cassava (Manihot esculenta Crantz), a primary food crop in the
      tropics. With the exception of Mononychellus tanajoa (Bondar), their geographic
      distribution is not widely known. This article therefore reports observational
      and specimen-based occurrence data of Mononychellus species associated with
      cassava. The dataset consists of 1,513 distribution records documented by the
      International Center for Tropical Agriculture (CIAT) between 1975 and 2012. The
      specimens are held at CIAT's Arthropod Reference Collection (CIATARC). Most of
      the records are from the genus' native range in South America and were documented
      between 1980 and 2000. Approximately 61% of the records belong to M. tanajoa, 25%
      to M. caribbeanae (McGregor), 10% to M. mcgregori (Flechtmann and Baker) and 2%
      to M. planki (McGregor). The complete dataset is available in Darwin Core Archive
      format via the Global Biodiversity Information Facility (GBIF). 

PMID- 24899827
TI  - Emerging trends in hepatocellular carcinoma: focus on diagnosis and therapeutics.
AB  - Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and one
      of the deadliest. Patients with chronic liver disease are at the highest risk for
      developing this tumor. This link provides an opportunity for developing
      preventive strategies and surveillance that aims at early detection of this tumor
      and possibly improving outcomes. In this review, we will discuss the latest
      developments in surveillance strategies, diagnosis, and treatment of this tumor.
      HCC is the sixth most common cancer in the world, with 782,000 new cases
      occurring in 2012 worldwide. In 2012, there were 746,000 deaths from liver
      cancer.1 HCC is the third most fatal cancer in the world.2 The distribution of
      HCC, which varies geographically, is related to the prevalence of hepatotropic
      virus. The burden of the disease is the highest in Eastern Asia, sub-Saharan
      Africa, and Melanesia where hepatitis B (HBV) infection is endemic. Meanwhile, in
      Japan, United States, and Europe, hepatitis C (HCV) infection is prevalent, and
      subsequently, is the major risk factor for acquiring HCC in these regions.1,3 It
      is estimated that the incidence of HCC in Europe and United States will peak at
      2020-there will be 78,000 new HCC cases in Europe and 27,000 in the United States
      and decline thereafter.1 Indeed, in Japan, the incidence of HCC had already
      plateaued and started to slowly fall.4 Cirrhosis is the most important risk
      factor for HCC regardless of etiology and may be caused by chronic viral
      hepatitis (mainly HBV and HCV), alcoholic liver disease, autoimmune disease,
      Stage 4 primary biliary cirrhosis, and metabolic diseases such as hereditary
      hemochromatosis, alpha-1 antitrypsin deficiency, and non-alcoholic fatty liver
      disease. In the Western hemisphere, HCC occurs in a background of cirrhosis in
      90% of the cases.5 Before concentrating on diagnosis and therapeutics, it is
      important to discuss surveillance for this tumor. 

PMID- 24899829
TI  - A new species of shrimp of the genus Anachlorocurtis Hayashi, 1975 from the Red
      Sea, with range extension of A. commensalis Hayashi, 1975 (Crustacea, Decapoda,
      Pandalidae).
AB  - A new species of pandalid shrimp Anachlorocurtis occidentalis sp. n., associated
      with antipatharian corals, is described and illustrated from the north-eastern
      Red Sea. This new species is closely related to Anachlorocurtis commensalis
      Hayashi, 1975, the only other species in the genus, and can be distinguished by
      the more slender body and appendages; the carapace with 3 large, and one small,
      subtriangular lobes in the middorsal line; a flattened dorsal outline of the
      third abdominal segment; the sixth abdominal segment twice as long as fifth one;
      propodi of the ambulatory pereiopods bearing only a single posterior spinule; and
      harbouring 3-5 pairs of dorsolateral spines on the telson. A revised generic
      diagnosis is provided here to accommodate the present new species. The genetic
      divergence of mitochondrial gene cytochrome c oxidase subunit I (COI) between
      Anachlorocurtis occidentalis sp. n., and A. commensalis is 15.2-15.4%. Molecular
      analysis also confirmed a sister position of the genus Anachlorocurtis to
      Miropandalus. The present records of A. commensalis from Taiwan constitute an
      extension of the known range of the species. 

PMID- 24899830
TI  - The genus Omalus Panzer, 1801 (Hymenoptera, Chrysididae) from China, with
      descriptions of four new species.
AB  - The Chinese species of the genus Omalus Panzer, 1801 are revised and keyed for
      the first time. Eight species are recorded, of which four are new to science and
      one is new to China: Omalus aeneus (Fabricius, 1787), Omalus berezovskii (Semenov
      Tian-Shanskij, 1932), Omalus potanini (Semenov-Tian-Shanskij, 1932), Omalus
      imbecillus (Mocsary, 1889) (new to China), Omalus helanshanus sp. n., Omalus
      probiaccinctus sp. n., Omalus pseudoimbecillus sp. n., and Omalus tibetanus sp.
      n. 

PMID- 24899831
TI  - Inventory of the carabid beetle fauna of the Gaoligong Mountains, western Yunnan
      Province, China: species of the tribe Zabrini (Coleoptera, Carabidae).
AB  - A ten-year multidisciplinary, multi-national and multi-institutional biodiversity
      inventory project in the Gaoligong Shan region of western Yunnan Province, China
      generated more than 35,000 specimens of the beetle (Coleoptera) family Carabidae.
      In this report, first of a planned series, we focus on diversity in tribe
      Zabrini. Our study of just over 1300 specimens of zabrine carabids from the
      project, all in genus Amara Bonelli, found a total of 13 species, all previously
      described, to occur in the study area, with none of them strictly endemic. We
      present a key for identification of adults of these species, as well as
      nomenclatural data, diagnoses, illustrations of dorsal habitus and male
      genitalia, and information about geographical, altitudinal and habitat
      distributions within the study area and overall geographical distribution for
      each species. Distributions of the species within the study area are compared,
      and broader geographical range patterns are characterized. We also discuss a
      possible role of the Gaoligong Shan region as one source area for the present-day
      fauna of the Himalaya and southern edge of the Qinghai-Xizang (Tibetan) Plateau. 

PMID- 24899833
TI  - Melitid amphipods from the Gulf of Thailand, with a description of Dulichiella
      pattaniensis, a new species.
AB  - Two species of melitid amphipod were collected from the Gulf of Thailand.
      Dulichiella pattaniensis is new to science, and Melitalati latiflagella Ren &
      Andres, 2012 has not been previously reported from Thai Waters. Dulichiella
      pattaniensis is characterized by male gnathopod 2 distolateral crown with 4
      spines; pleonite/urosomite formula 7-7-7-5-6-2; pereopod 5-7 dactylus with 2
      accessory spines. This combination of characters has not been recorded previously
      in the Dulichiella. The characters of the specimens are described and
      illustrated. All specimens are deposited in the Princess Maha Chakri Sirindhorn
      Natural History Museum, Prince of Songkla University, Thailand. 

PMID- 24899832
TI  - Phylogenetic relationships of Malaysia's long-tailed macaques, Macaca
      fascicularis, based on cytochrome b sequences.
AB  - Phylogenetic relationships among Malaysia's long-tailed macaques have yet to be
      established, despite abundant genetic studies of the species worldwide. The aims
      of this study are to examine the phylogenetic relationships of Macaca
      fascicularis in Malaysia and to test its classification as a morphological
      subspecies. A total of 25 genetic samples of M. fascicularis yielding 383 bp of
      Cytochrome b (Cyt b) sequences were used in phylogenetic analysis along with one
      sample each of M. nemestrina and M. arctoides used as outgroups. Sequence
      character analysis reveals that Cyt b locus is a highly conserved region with
      only 23% parsimony informative character detected among ingroups. Further
      analysis indicates a clear separation between populations originating from
      different regions; the Malay Peninsula versus Borneo Insular, the East Coast
      versus West Coast of the Malay Peninsula, and the island versus mainland Malay
      Peninsula populations. Phylogenetic trees (NJ, MP and Bayesian) portray a
      consistent clustering paradigm as Borneo's population was distinguished from
      Peninsula's population (99% and 100% bootstrap value in NJ and MP respectively
      and 1.00 posterior probability in Bayesian trees). The East coast population was
      separated from other Peninsula populations (64% in NJ, 66% in MP and 0.53
      posterior probability in Bayesian). West coast populations were divided into 2
      clades: the North-South (47%/54% in NJ, 26/26% in MP and 1.00/0.80 posterior
      probability in Bayesian) and Island-Mainland (93% in NJ, 90% in MP and 1.00
      posterior probability in Bayesian). The results confirm the previous
      morphological assignment of 2 subspecies, M. f. fascicularis and M. f.
      argentimembris, in the Malay Peninsula. These populations should be treated as
      separate genetic entities in order to conserve the genetic diversity of
      Malaysia's M. fascicularis. These findings are crucial in aiding the conservation
      management and translocation process of M. fascicularis populations in Malaysia. 

PMID- 24899834
TI  - Three new bamboo-feeding species of the genus Symplanella Fennah (Hemiptera,
      Fulgoromorpha, Caliscelidae) from China.
AB  - Three new species of the Oriental caliscelid planthopper genus Symplanella
      Fennah, S. hainanensis sp. n., S. recurvata sp. n. and S. zhongtua sp. n., are
      described and illustrated from South China. A checklist and a key to species of
      genus Symplanella are provided. 

PMID- 24899835
TI  - AnthWest, occurrence records for wool carder bees of the genus Anthidium
      (Hymenoptera, Megachilidae, Anthidiini) in the Western Hemisphere.
AB  - This paper describes AnthWest, a large dataset that represents one of the
      outcomes of a comprehensive, broadly comparative study on the diversity, biology,
      biogeography, and evolution of Anthidium Fabricius in the Western Hemisphere. In
      this dataset a total of 22,648 adult occurrence records comprising 9657 unique
      events are documented for 92 species of Anthidium, including the invasive range
      of two introduced species from Eurasia, A. oblongatum (Illiger) and A. manicatum
      (Linnaeus). The geospatial coverage of the dataset extends from northern Canada
      and Alaska to southern Argentina, and from below sea level in Death Valley,
      California, USA, to 4700 m a.s.l. in Tucuman, Argentina. The majority of records
      in the dataset correspond to information recorded from individual specimens
      examined by the authors during this project and deposited in 60 biodiversity
      collections located in Africa, Europe, North and South America. A fraction (4.8%)
      of the occurrence records were taken from the literature, largely California
      records from a taxonomic treatment with some additional records for the two
      introduced species. The temporal scale of the dataset represents collection
      events recorded between 1886 and 2012. The dataset was developed employing SQL
      server 2008 r2. For each specimen, the following information is generally
      provided: scientific name including identification qualifier when species status
      is uncertain (e.g. "Questionable Determination" for 0.4% of the specimens), sex,
      temporal and geospatial details, coordinates, data collector, host plants,
      associated organisms, name of identifier, historic identification, historic
      identifier, taxonomic value (i.e., type specimen, voucher, etc.), and repository.
      For a small portion of the database records, bees associated with threatened or
      endangered plants (~ 0.08% of total records) as well as specimens collected as
      part of unpublished biological inventories (~17%), georeferencing is presented
      only to nearest degree and the information on floral host, locality, elevation,
      month, and day has been withheld. This database can potentially be used in
      species distribution and niche modeling studies, as well as in assessments of
      pollinator status and pollination services. For native pollinators, this large
      dataset of occurrence records is the first to be simultaneously developed during
      a species-level systematic study. 

PMID- 24899836
TI  - Umashtanchaeviella plethotricha, a new genus and species of the family
      Tetracondylidae (Acari, Oribatida).
AB  - A new genus of oribatid mites of the family Tetracondylidae, Umashtanchaeviella
      gen. n., with type species Umashtanchaeviella plethotricha sp. n., is proposed
      and described from forest litter, the Bu Gia Map National Park, southern Vietnam.
      The new genus is distinguishable from other otocepheoid genera by the presence of
      notogastral plethotrichy. 

PMID- 24899837
TI  - A peculiar cave species of Tomocerus (Collembola, Tomoceridae, Tomocerinae) from
      Vietnam, with a discussion of the postantennal organ and prelabral chaetae in
      Tomocerinae.
AB  - The first Tomocerus species with a postantennal organ (PAO) in the adult stage is
      described from Vietnam. Tomocerus postantennalis sp. n. differs from the other
      PAO-possessing tomocerid, Tomolonus reductus Mills, 1948, mainly in the
      morphology of PAO, the number of ocelli, the number of chaetae in trochantero
      femoral organ and several features of the furca. The new species is placed in
      Tomocerus because of the presence of a toothlet on the outer basal mucronal tooth
      and the absence of the diagnostic character states of Plutomurus Yosii, 1956 and
      Aphaenomurus Yosii, 1956. Besides the presence of PAO, the new species is
      peculiar in having six prelabral chaetae, instead of four as in other Tomocerus
      species. The new species is similar to Tomocerus folsomi Denis, 1929 and
      Tomocerus ocreatus Denis, 1948 in the type of dental spines but different from
      them in the body colour, the relative length of antennae to body, the number of
      unguis inner teeth and the number of mucronal intermediate teeth. 

PMID- 24899838
TI  - A new species in the genus Amphipteryx Selys, 1853 (Odonata, Amphipterygidae)
      from Pico Bonito National Park, Honduras.
AB  - The Mesoamerican damselfly genus Amphipteryx includes four species: Amphipteryx
      agrioides (Mexico), A. chiapensis (Mexico), A. meridionalis (Honduras) and A.
      nataliae (Verapaz, Guatemala). We describe a fifth species, Amphipteryx jaroli,
      from the cloud forest in Pico Bonito National park, Honduras. Additionally we
      include an up to date key of all species in the genus for both sexes. 

PMID- 24899839
TI  - New tardigrade records for the Baltic states with a description of Minibiotus
      formosus sp. n. (Eutardigrada, Macrobiotidae).
AB  - In sixteen moss, lichen and mixed (moss/lichen) samples, collected from Estonia,
      Latvia and Lithuania, 291 specimens, 48 simplexes, including one exuvium with 6
      eggs, and 8 free-laid eggs of eutardigrades were found. In total, 17 species,
      together with one new to science, were identified (all are new records for the
      Baltic states): Astatumen bartosi, Diphascon (Adropion) prorsirostre, D.
      (Diphascon) bullatum, D. (D.) pingue pingue, D. (D.) recamieri, D. (D.) rugosum,
      Hypsibius convergens, H. dujardini, H. cf. scabropygus, Isohypsibius
      ronsisvallei, I. sattleri, Macrobiotus harmsworthi harmsworthi, M. hufelandi
      hufelandi, Milnesium asiaticum, Milnesium tardigradum tardigradum, Minibiotus
      formosus sp. n. and Paramacrobiotus richtersi. The new species is most similar to
      Minibiotus gumersindoi, but differs from it mainly by the presence of two types
      of cuticular pores, the absence of a triangular or pentagonal arrangement of
      pores above a single large pore on legs, the presence of granulation on all legs
      and a different macroplacoid length sequence. In this paper we also provide
      photographs and morphometrics of H. cf. scabropygus. 

PMID- 24899840
TI  - Description of Medwayella independencia (Siphonaptera, Stivaliidae), a new
      species of flea from Mindanao Island, the Philippines and their phoretic mites,
      and miscellaneous flea records from the Malay Archipelago.
AB  - Medwayella independencia, a new species of flea, is described from the tupaiid
      host Urogale everetti (Thomas) from Mindanao Island, Philippines. Several other
      species of fleas are also recorded from the Philippines including a single male
      of Lentistivalius philippinensis Hastriter and Bush, 2013 (previously known only
      from two males), the bat fleas Thaumapsylla breviceps orientalis Smit and
      Thaumapsylla longiforceps Traub, a single unidentified female species of
      Macrostylophora Ewing collected from the murid Bullimus bagobos Mearns, and a
      pair of Medwayella robinsoni ssp. from Sundasciurus hoogstraali (Sanborn) from
      Busuanga Island, Philippines. Representatives of Medwayella Traub, 1972 and
      Macrostylophora have not previously been recorded from the Philippines. A key to
      the male sex of Medwayella is provided. Phoretic mites of the genus Psylloglyphus
      (family Winterschmidtiidae) were present under the abdominal sclerites of several
      male and female specimens of M. independencia. This is the second report of a
      phoretic mite on a species of Medwayella Traub. The co-evolutionary implications
      between phoretic mites and fleas are discussed. 

PMID- 24899842
TI  - Reevaluation of the odd chrysidid genus Atoposega Krombein (Hymenoptera,
      Chrysididae, Amiseginae).
AB  - The south Asian amisegine genus Atoposega Krombein, 1957, is reevaluated. Three
      new species, A. rufithorax, A. striata and A. thailandica are described from
      Thailand and the previously described species, A. lineata (Krombein, 1957) from
      Borneo, A. rieki (Krombein, 1957) from Myanmar and A. simulans Kimsey, 1986 from
      Malaysia are redescribed. The species, A. decorata Kimsey, 1995, was found to
      lack the generic characters diagnostic for Atoposega. Atoposega is only known
      from females. 

PMID- 24899841
TI  - Biogeography and taxonomy of extinct and endangered monk seals illuminated by
      ancient DNA and skull morphology.
AB  - Extinctions and declines of large marine vertebrates have major ecological
      impacts and are of critical concern in marine environments. The Caribbean monk
      seal, Monachus tropicalis, last definitively reported in 1952, was one of the few
      marine mammal species to become extinct in historical times. Despite its
      importance for understanding the evolutionary biogeography of southern phocids,
      the relationships of M. tropicalis to the two living species of critically
      endangered monk seals have not been resolved. In this study we present the first
      molecular data for M. tropicalis, derived from museum skins. Phylogenetic
      analysis of cytochrome b sequences indicates that M. tropicalis was more closely
      related to the Hawaiian rather than the Mediterranean monk seal. Divergence time
      estimation implicates the formation of the Panamanian Isthmus in the speciation
      of Caribbean and Hawaiian monk seals. Molecular, morphological and temporal
      divergence between the Mediterranean and "New World monk seals" (Hawaiian and
      Caribbean) is profound, equivalent to or greater than between sister genera of
      phocids. As a result, we classify the Caribbean and Hawaiian monk seals together
      in a newly erected genus, Neomonachus. The two genera of extant monk seals
      (Monachus and Neomonachus) represent old evolutionary lineages each represented
      by a single critically endangered species, both warranting continuing and
      concerted conservation attention and investment if they are to avoid the fate of
      their Caribbean relative. 

PMID- 24899843
TI  - Supplement to the revision of the genus Eremosaprinus Ross, 1939 (Coleoptera,
      Histeridae, Saprininae): new distributional data and description of a new species
      from Arizona, U.S.A.
AB  - A new species of the genus Eremosaprinus Ross, 1939, E. warneri, is described
      from southeastern Arizona, USA, and incorporated into the identification key for
      the genus. Description of the new species is supplemented with SEM micrographs
      and drawings of sensory structures of the antenna and male genitalia. New
      distribution data on four species, E. distinctus Lundgren, 1992, E. hubbardi
      (Wenzel, 1939), E. minimus Tishechkin & Lackner, 2012, and E. unguiculatus (Ross,
      1939), are also provided. 

PMID- 24899844
TI  - The South American radiation of Jerrybuccinum (Gastropoda, Buccinidae), with a
      new deep-water species from Chile.
AB  - A new deep water species from off the Chilean coast, Jerrybuccinum kantori sp.
      n., is described. The animal is equipped with a large statocyst. Kryptos
      explorator Fraussen & Sellanes, 2008 from off Concepcion is found to be
      congeneric and transferred to the genus Jerrybuccinum. Differences in size and
      sculpture serve to distinguish the new species from J. explorator. Both Chilean
      species are associated with methane seep or low oxygen environments. They are
      compared with J. malvinense Kantor & Pastorino, 2009 and two still unnamed
      species from the Falkland Plateau. 

PMID- 24899845
TI  - A new Liopropoma sea bass (Serranidae, Epinephelinae, Liopropomini) from deep
      reefs off Curacao, southern Caribbean, with comments on depth distributions of
      western Atlantic liopropomins.
AB  - Collecting reef-fish specimens using a manned submersible diving to 300 m off
      Curacao, southern Caribbean, is resulting in the discovery of numerous new fish
      species. The new Liopropoma sea bass described here differs from other western
      Atlantic members of the genus in having VIII, 13 dorsal-fin rays; a moderately
      indented dorsal-fin margin; a yellow-orange stripe along the entire upper lip; a
      series of approximately 13 white, chevron-shaped markings on the ventral portion
      of the trunk; and a reddish-black blotch on the tip of the lower caudal-fin lobe.
      The new species, with predominantly yellow body and fins, closely resembles the
      other two "golden basses" found together with it at Curacao: L. aberrans and L.
      olneyi. It also shares morphological features with the other western Atlantic
      liopropomin genus, Bathyanthias. Preliminary phylogenetic data suggest that
      western Atlantic liopropomins, including Bathyanthias, are monophyletic with
      respect to Indo-Pacific Liopropoma, and that Bathyanthias is nested within
      Liopropoma, indicating a need for further study of the generic limits of
      Liopropoma. The phylogenetic data also suggest that western Atlantic liopropomins
      comprise three monophyletic clades that have overlapping depth distributions but
      different depth maxima (3-135 m, 30-150 m, 133-411 m). The new species has the
      deepest depth range (182-241 m) of any known western Atlantic Liopropoma species.
      Both allopatric and depth-mediated ecological speciation may have contributed to
      the evolution of western Atlantic Liopropomini. 

PMID- 24899846
TI  - A new species of Dysanabatium Bernhauer and additional records of D. jacobsoni
      Bernhauer (Coleoptera, Staphylinidae, Paederinae).
AB  - Dysanabatium hainanense Peng & Li, sp. n. (Hainan: Wuzhi Shan, Diaoluo Shan) is
      described and illustrated. Additional records of D. jacobsoni Bernhauer, 1915 are
      reported. The habitus, the sexual characters, and the distribution of this
      enormously variable species are illustrated. 

PMID- 24899847
TI  - A new species of Dystacta Saussure, 1871 from Nyungwe National Park, Rwanda
      (Insecta, Mantodea, Dystactinae).
AB  - A recent targeted entomological survey in the Republic of Rwanda has produced two
      conspecific male and female specimens of an undescribed species of praying mantis
      (Mantodea). The specimens were collected in Nyungwe National Park in May of 2013.
      The species is closest morphologically to Dystacta alticeps (Schaum, 1853).
      Therefore, a new species is described, Dystacta tigrifrutex sp. n., along with
      the first instar nymphs and ootheca. In addition, the previously monotypic genus
      Dystacta Saussure, 1871 is re-described to provide a broader definition of the
      genus group. Habitus images, measurement data, a key to species, natural history
      information, and locality data are provided. 

PMID- 24899848
TI  - A review of the microgastropod genus Systenostoma Bavay & Dautzenberg, 1908 and a
      new subterranean species from China (Gastropoda, Pulmonata, Hypselostomatidae).
AB  - A review of the microgastropod genus Systenostoma is provided. Thai and Malaysian
      species are transferred to a new genus, Angustopila (type species: Systenostoma
      tamlod Panha & Burch, 1999). A new subterranean Angustopila species is described
      here. Conchologically, the new species is most similar to the cave-dwelling, Thai
      A. tamlod (Panha & Burch, 1999). One Thai species (Systenostoma edentata) is
      transferred to the genus Hypselostoma. Vietnamese members remain in the genus
      Tonkinospira (nomen novum) for Systenostoma Bavay & Dautzenberg, 1908 (non
      Systenostoma Marsson, 1887). A comprehensive map of former Systenostoma species
      is presented. SEM and NanoCT images, including a video of A. huoyani sp. n.
      internal shell morphology, provide novel perspectives of the shells of
      Angustopila and of the scarcely known Vietnamese Tonkinospira species. The
      biology of these snails is not yet known but collection localities suggest a
      troglophilic ecology. 

PMID- 24899849
TI  - Calcaridorylaimus castaneae sp. n. (Nematoda, Dorylaimidae) from Bulgaria with an
      identification key to the species of the genus.
AB  - An unknown species belonging to the genusCalcaridorylaimus Andrassy, 1986 was
      collected from the litter of broadleaf forests dominated by Castanea sativa Mill.
      and mixed with Quercus daleshampii Ten. and Fagus sylvatica L. on Belasitsa
      Mountain, south-western Bulgaria. Calcaridorylaimus castaneae sp. n. is
      characterised by its long body (1.4-2.1 mm), lip region practically not offset,
      vulva transverse, short odontostyle (14.5-16 MUm) and tail (75.5-110.5 MUm,
      c=14.7-23.6; c'=2.9-4.4) in females and 38-46 MUm long spicules with small spur
      before their distant end in males. It is most similar to C. andrassyi Ahmad &
      Shaheen, 2004, but differs in having transverse vs pore-like vulva and shorter
      spicules (38-46 MUm vs 52-57 MUm). An identification key to the species of the
      genus Calcaridorylaimus is proposed. Phylogenetic analyses were performed on 18S
      and D2-D3 expansion domains of 28S rRNA genes by Neighbor-Joining, Maximum
      Likelihood and Bayesian Inference methods. The phylograms inferred from 18S
      sequences showed closest relationships of the new species with some species
      belonging to the genus Mesodorylaimus. However, insufficient molecular data for
      members of both genera do not allow the phylogenetic relationships of
      Calcaridorylaimus and the new species described herein to be elucidated. 

PMID- 24899850
TI  - Taxonomic notes on the genus Eupoa Zabka, 1985 (Arachnida, Araneae, Salticidae).
AB  - The south-east Asian genus Eupoa is redescribed and diagnosed. Seven new species
      are diagnosed, described and illustrated: E. daklak sp. n. (?) from Viet-Nam; E.
      lehtineni sp. n. (??) from India, Thailand and Viet-Nam; E. lobli sp. n. (?) from
      Malaysia; E. pappi sp. n. (?) from Thailand; E. pulchella sp. n.(?) from
      Thailand; E. schwendingeri sp. n. (??) from Thailand; and E. thailandica sp. n.
      (??) from Thailand. Eupoa prima Zabka, 1985 and E. yunnanensis Peng & Kim, 1997
      are redescribed and illustrated on the basis of type and/or newly collected
      materials. The female of E. yunnanensis Peng & Kim, 1997 is found and described
      for the first time. 

PMID- 24899851
TI  - Birds of Antioquia: Georeferenced database of specimens from the Coleccion de
      Ciencias Naturales del Museo Universitario de la Universidad de Antioquia (MUA).
AB  - The department of Antioquia, Colombia, lies in the northwestern corner of South
      America and provides a biogeographical link among divergent faunas, including
      Caribbean, Andean, Pacific and Amazonian. Information about the distribution of
      biodiversity in this area is of relevance for academic, practical and social
      purposes. This data paper describes the dataset containing all bird specimens
      deposited in the Coleccion de Ciencias Naturales del Museo Universitario de la
      Universidad de Antioquia (MUA). We curated all the information associated with
      the bird specimens, including the georeferences and taxonomy, and published the
      database through the Global Biodiversity Information Facility network. During
      this process we checked the species identification and existing georeferences and
      completed the information when possible. The collection holds 663 bird specimens
      collected between 1940 and 2011. Even though most specimens are from Antioquia
      (70%), the collection includes material from several other departments and one
      specimen from the United States. The collection holds specimens from three
      endemic and endangered species (Coeligena orina, Diglossa gloriossisima, and
      Hypopirrhus pyrohipogaster), and includes localities poorly represented in other
      collections. The information contained in the collection has been used for
      biodiversity modeling, conservation planning and management, and we expect to
      further facilitate these activities by making it publicly available. 

PMID- 24899852
TI  - A new species of Alopoglossus lizard (Squamata, Gymnophthalmidae) from the
      tropical Andes, with a molecular phylogeny of the genus.
AB  - We describe a new species of Alopoglossus from the Pacific slopes of the Andes in
      northern Ecuador based on morphological and molecular evidence. The new species
      differs most significantly from all other congeners in having a double
      longitudinal row of widened gular scales, lanceolate dorsal scales in transverse
      rows, 29-32 dorsal scales in a transverse row at midbody, and 4 longitudinal rows
      of ventrals at midbody. It is most similar in morphology to A. festae, the only
      species of Alopoglossus currently recognized in western Ecuador. We analyze the
      phylogenetic relationships among species of Alopoglossus based on the
      mitochondrial gene ND4. Cis-Andean [east of the Andes] and Trans-Andean [west of
      the Andes] species are nested in two separate clades, suggesting that the uplift
      of these mountains had an important effect in the diversification of
      Alopoglossus. In addition, we present an updated key to the species of
      Alopoglossus. 

PMID- 24899853
TI  - Four new Mouse Spider species (Araneae, Mygalomorphae, Actinopodidae, Missulena)
      from Western Australia.
AB  - Four new species of the Mouse Spider genus Missulena Walckenaer, 1805 (family
      Actinopodidae) are described from Western Australia based on morphological
      features of adult males. Missulena leniae sp. n.(from the Carnarvon and Yalgoo
      biogeographic regions), Missulena mainae sp. n. (Carnarvon), Missulena melissae
      sp. n. (Pilbara) and Missulena pinguipes sp. n. (Mallee) represent a broad
      spectrum of morphological diversity found in this genus and differ from other
      congeners by details of the male copulatory bulb, colour patterns, eye sizes, leg
      morphology and leg spination. Two of the species, M. pinguipes sp. n. and M.
      mainae sp. n., are characterised by swollen metatarsi of the fourth legs in
      males, a feature not previously recorded in the family. A key to males of all
      named Missulena species from Australia is presented and allows their
      identification based on external morphology. 

PMID- 24899854
TI  - An annotated catalogue of type specimens of the land snail genus Cyclophorus
      Monfort, 1810 (Caenogastropoda, Cyclophoridae) in the Natural History Museum,
      London.
AB  - The collection of land caenogastropod snails in the genus Cyclophorus Monfort,
      1810 housed in the Natural History Museum, London (NHM), includes 52 type lots.
      Lectotypes have been designated for 43 available species-level names to stabilize
      existing nomenclature, two previously designated lectotype, two holotypes, one
      paratype, one syntype, one possible syntype and two paralectotypes are also
      listed. A complete catalogue of the Cyclophorus types in NHM, London is provided
      for the first time. 

PMID- 24899856
TI  - The ant genus Tetramorium Mayr in the Afrotropical region (Hymenoptera,
      Formicidae, Myrmicinae): synonymisation of Decamorium Forel under Tetramorium,
      and taxonomic revision of the T. decem species group.
AB  - In this study we synonymise the genus Decamorium Forel under Tetramorium Mayr,
      revise the new T. decem species group by providing a diagnosis of the group, an
      illustrated identification key to species level, and worker-based species
      descriptions for all five species, which include diagnoses, discussions, images,
      and distribution maps. The following species are revised in this study: T. decem
      Forel, comb. r., T. raptor sp. n., T. uelense Santschi, comb. r., T. ultor Forel,
      comb. r., stat. r. & stat. n., and T. venator sp. n. In addition, we also
      designate lectotypes for T. decem, T. uelense, and T. ultor. 

PMID- 24899855
TI  - A new Pseudophoxinus (Teleostei, Cyprinidae) species from Asi River Drainage
      (Turkey).
AB  - Pseudophoxinus turani sp. n. is described from the Incesu Spring (Hassa-Hatay)
      drainage of Asi River, Turkey. It is distinguished from other Eastern
      Mediterranean Region Pseudophoxinus species by a combination of characters:
      lateral line incomplete, with 12-25 (commonly 16-21) perforated scales and 38
      46+2-3 scales in lateral series (commonly 41-44+2-3); 10-11 scale rows between
      the lateral line and dorsal-fin origin; 3-4 scale rows between the lateral line
      and the pelvic-fin origin; dorsal fin with 71/2 branched rays; anal fin commonly
      with 71/2 branched rays; 8-11gill rakers on the first branchial arch; dorsal
      profile markedly convex with marked hump at the nape, ventral profile less convex
      than dorsal profile; a small, irregular, black blotch on the base of the caudal
      fin; mouth terminal, with slightly distinct chin, its corner not reaching
      vertical through anterior margin of eye; snout somewhat long, with rounded tip;
      and its length greater than eye diameter. 

PMID- 24899857
TI  - Morphological and molecular affinities of two East Asian species of Stenhelia
      (Crustacea, Copepoda, Harpacticoida).
AB  - Definition of monophyletic supraspecific units in the harpacticoid subfamily
      Stenheliinae Brady, 1880 has been considered problematic and hindered by the lack
      of molecular or morphology based phylogenies, as well as by incomplete original
      descriptions of many species. Presence of a modified seta on the fifth leg
      endopod has been suggested recently as a synapomorphy of eight species comprising
      the redefined genus Stenhelia Boeck, 1865, although its presence was not known in
      S. pubescens Chislenko, 1978. We redescribe this species in detail here, based on
      our freshly collected topotypes from the Russian Far East. The other species
      redescribed in this paper was collected from the southern coast of South Korea
      and identified as the Chinese S. taiae Mu & Huys, 2002, which represents its
      second record ever and the first one in Korea. A fragment of the mtCOI gene was
      successfully PCR-amplified from two specimens of each species, which represents
      the first molecular data for this genus, and from additional 19 specimens
      belonging to six different species of other stenheliins from Korea and Russia.
      Reconstructed phylogenies confirm previously postulated monophyly of Stenhelia
      and polyphyly of the closely related genus Delavalia Brady, 1869. Average
      pairwise maximum likelihood distances between S. pubescens and S. taiae are only
      slightly above 10%, suggesting a very close relationship despite numerous newly
      discovered micro-morphological differences and despite macro-morphological
      similarities being probable plesiomorphies. 

PMID- 24899858
TI  - Two new species of Trichoceridae from the Middle Jurassic Jiulongshan Formation
      of Inner Mongolia, China.
AB  - Two new species, Eotrichocera (Archaeotrichocera) longensis sp. n. and
      Eotrichocera (Archaeotrichocera) amabilis sp. n. of Trichoceridae are described
      based on a combination of the following characters: Sc ending proximad of the
      forking of R2, shape of d cell and A2 rather short and bending sharply toward
      posterior margin. These fossil specimens were collected from the Middle Jurassic
      Jiulongshan Formation of Daohugou in Inner Mongolia, China. 

PMID- 24899859
TI  - Notes on the genus Microcriodes Breuning, with description of a new species from
      Xizang, China (Coleoptera, Cerambycidae, Lamiinae, Batocerini).
AB  - The genus Microcriodes Breuning is newly recorded from China upon the discovery
      of M. sikkimensis Breuning, 1943 and M. wuchaoi sp. n. from Motuo, Southeast
      Xizang. Illustrations of the habitus, genitalia including non-everted
      endophallus, as well as diagnostic features are provided. 

PMID- 24899860
TI  - Review of Canadian species of the genera Gnathusa Fenyes, Mniusa Mulsant & Rey
      and Ocyusa Kraatz (Coleoptera, Staphylinidae, Aleocharinae).
AB  - Four species of Gnathusa Fenyes (G. alfacaribou Klimaszewski & Langor, G. caribou
      Lohse, G. eva Fenyes, and G. tenuicornis Fenyes) occur in the Nearctic and in
      Canada. Three species of Ocyusa Kraatz (O. asperula Casey, O. californica
      Bernhauer, O. canadensis Lohse), and three species of Mniusa Mulsant and Ray (M.
      minutissima (Klimaszewski & Langor), M. yukonensis (Klimaszewski & Godin), and M.
      odelli Klimaszewski & Webster, sp. n.), are known from the Nearctic and all but
      O. californica occur in Canada. The recently described Gnathusa minutissima
      Klimaszewski and Langor and Ocyusa yukonensis Klimaszewski and Godin, are
      transferred here to the genus Mniusa Mulsant & Rey. New provincial and state
      records are reported for: G. eva (Alberta), G. tenuicornis (Alberta, Oregon, and
      New Brunswick), O. canadensis (New Brunswick and Newfoundland), M. minutissima
      (New Brunswick), and M. yukonensis (Nova Scotia, New Brunswick, Quebec, and
      British Columbia). The female of M. yukonensis was discovered and is illustrated
      for the first time. The genus Mniusa is reported for the first time from Canada
      and represents the first confirmed generic record for North America. Keys for
      identification of all Canadian species, images of body and genital structures,
      maps showing distribution mainly in Canada, and new bionomics data are provided. 

PMID- 24899861
TI  - The Hoosier cavefish, a new and endangered species (Amblyopsidae, Amblyopsis)
      from the caves of southern Indiana.
AB  - WE DESCRIBE A NEW SPECIES OF AMBLYOPSID CAVEFISH (PERCOPSIFORMES: Amblyopsidae)
      in the genus Amblyopsis from subterranean habitats of southern Indiana, USA. The
      Hoosier Cavefish, Amblyopsis hoosieri sp. n., is distinguished from A. spelaea,
      its only congener, based on genetic, geographic, and morphological evidence.
      Several morphological features distinguish the new species, including a much
      plumper, Bibendum-like wrinkled body with rounded fins, and the absence of a
      premature stop codon in the gene rhodopsin. This is the first new cavefish
      species described from the United States in 40 years and exemplifies how
      molecular data can alert us to the presence of otherwise cryptic biodiversity.

PMID- 24899862
TI  - Revision of the genus Salganea Stal (Blattodea, Blaberidae, Panesthiinae) from
      China, with descriptions of three new species.
AB  - Three new species of Salganea Stal, 1877 are described and illustrated: S.
      quinquedentata sp. n., S. anisodonta sp. n. and S. flexibilis sp. n. S.
      taiwanensis Roth, 1979, S. guangxiensis (Feng & Woo, 1990), S. incerta (Brunner
      von Wattenwyl, 1893) and S. raggei Roth, 1979 are redescribed. Panesthia concinna
      Feng & Woo, 1990 is synonymized with S. taiwanensis Roth, 1979 and Panesthia
      guangxiensis Feng & Woo, 1990 is transferred to the genus Salganea for the first
      time. As well, a key to species from China is presented. 

PMID- 24899863
TI  - The invasion history, distribution and colour pattern forms of the harlequin
      ladybird beetle Harmonia axyridis (Pall.) (Coleoptera, Coccinellidae) in
      Slovakia, Central Europe.
AB  - The harlequin ladybird beetle Harmonia axyridis (Coleoptera, Coccinellidae) has
      invaded and established in Slovakia. Following unintentional introduction in
      2008, the spread of the alien coccinellid was very fast. By the end of 2009, it
      was recorded across the whole country, and by the end of 2012 it was widely
      distributed and common in various habitats, particularly gardens, orchards and
      urban areas, where it was most frequent on trees. The rate of eastward spread was
      approximately 200 km year(-1), similar to the overall rate of spread in Europe.
      Between 2008 and 2012, the coccinellid was recorded in a total of 153 localities,
      in altitudes ranging from 98 to 1,250 m. Most records of this species were made
      in lowlands, hilly areas and valleys separating mountain ridges. However, it was
      only rarely documented in areas above 700 m a.s.l. The non-melanic colour form
      (f. succinea) was dominant along a longitudinal transect including eight urban
      areas across Slovakia, with the frequency of melanic forms (f. spectabilis and f.
      conspicua together) between 6.3 and 19.2% and a median equal to 10.5%. The
      invasion history and distribution of H. axyridis in Slovakia are discussed with
      regard to the time sequence of records, rate of spread, altitudinal distribution,
      anthropogenic dispersal, effective recording, proportion of melanic forms and
      other relevant aspects associated with the spread of this successful invader. 

PMID- 24899864
TI  - A new species of the genus Diplocentrus Peters, 1861 (Scorpiones, Diplocentridae)
      from Oaxaca, Mexico.
AB  - A new species of the genus Diplocentrus Peters, 1861 is described, based on
      several specimens collected in the Mexican state of Oaxaca. It is characterized
      by a high telotarsal spiniform setae count (4-5/5:5/6:6/6:6/6-7), and the
      pectinal tooth counts of 12-15, mode = 13 (male) or 11-13, mode = 12 (female).
      With the description of this species, the diversity of the genus is increased to
      51 species in Mexico. 

PMID- 24899865
TI  - Taxonomic notes on Cryptamorpha sculptifrons Reitter (Coleoptera, Silvanidae),
      with description of its larval morphology.
AB  - Cryptamorpha sculptifrons Reitter, 1889 is redescribed and a lectotype and
      paralectotype are designated. The mature larva of C. sculptifrons is described.
      It is hypothesized that a variety described by Grouvelle (1908), C. sculptifrons
      var. punctifrons from India, might not be conspecific with Japanese C.
      sculptifrons. It is also suggested that larvae of Cryptamorpha can be
      distinguished from larvae of the tribe Brontini by the relatively thick antennae
      and the 3rd antennomere which is less than 3/4 of the length of the 2nd. 

PMID- 24899866
TI  - Neoplasm seeding in biopsy tract of the musculoskeletal system. A systematic
      review.
AB  - To identify, through a systematic literature review, the characteristics of
      neoplasm seeding in biopsy performed on the musculoskeletal system. We performed
      a search on PubMed, MEDLINE, LILACS and SciELO from August to October 2010. We
      included articles that addressed the neoplasm seeding in biopsy performed on the
      musculoskeletal system. The search was limited to English, Spanish and Portuguese
      as publication languages, but it was not limited by year of publication. We
      retrieved 2858 articles, but only seven were selected based on inclusion and
      exclusion criteria. Other four papers were found in the references of selected
      articles, totalizing 11 articles that were used to perform this systematic
      review. Issues may be raised in the literature: age and gender don't seem to
      influence the occurrence of neoplasm seeding; without resection of the biopsy
      tract, the possibility of local recurrence is very real; the influence of the
      type of tumor in the occurrence of neoplasm seeding is uncertain; it is
      impossible to conclude whether the closed biopsy technique has a lower chance of
      neoplasm seeding; it is likely that adjuvant chemotherapy has a protective effect
      against neoplasm seeding; an unfavorable prognosis is expected according to
      neoplasm seeding results. 

PMID- 24899867
TI  - Zinc(II) Complexes with Dangling Functional Organic Groups.
AB  - Zinc(II) complexes with dangling functional organic groups were synthesized by
      reaction of zinc acetate with a series of bifunctional p-substituted benzene
      derivatives (a combination of carboxylate, oximate, amino, beta-ketoimine, and
      salicylaldime groups). Selective coordination to carboxylate groups was observed
      when the second functional group was an oxime or beta-ketoimine group. When the
      second group was an amine or salicylaldimine moiety, these groups were
      additionally coordinated. From the reaction with p-aminobenzoic acid, the
      compound [Zn2(OOCCH3)(OOC-C6H4-NH2)3]infinity was crystallized. It is a three
      dimensional coordination polymer with bridging aminobenzoate ligands.

PMID- 24899868
TI  - SPREADING SPEEDS AND TRAVELING WAVES FOR NON-COOPERATIVE INTEGRO-DIFFERENCE
      SYSTEMS.
AB  - The study of spatially explicit integro-difference systems when the local
      population dynamics are given in terms of discrete-time generations models has
      gained considerable attention over the past two decades. These nonlinear systems
      arise naturally in the study of the spatial dispersal of organisms. The brunt of
      the mathematical research on these systems, particularly, when dealing with
      cooperative systems, has focused on the study of the existence of traveling wave
      solutions and the characterization of their spreading speed. Here, we
      characterize the minimum propagation (spreading) speed, via the convergence of
      initial data to wave solutions, for a large class of non cooperative nonlinear
      systems of integro-difference equations. The spreading speed turns out to be the
      slowest speed from a family of non-constant traveling wave solutions. The
      applicability of these theoretical results is illustrated through the explicit
      study of an integro-difference system with local population dynamics governed by
      Hassell and Comins' non-cooperative competition model (1976). The corresponding
      integro-difference nonlinear systems that results from the redistribution of
      individuals via a dispersal kernel is shown to satisfy conditions that guarantee
      the existence of minimum speeds and traveling waves. This paper is dedicated to
      Avner Friedman as we celebrate his immense contributions to the fields of partial
      differential equations, integral equations, mathematical biology, industrial
      mathematics and applied mathematics in general. His leadership in the
      mathematical sciences and his mentorship of students and friends over several
      decades has made a huge difference in the personal and professional lives of
      many, including both of us.

PMID- 24899869
TI  - High-separation efficiency micro-fabricated multi-capillary gas chromatographic
      columns for simulants of the nerve agents and blister agents.
AB  - To achieve both high speed and separation efficiency in the separation of a
      mixture of nerve and blister agent simulants, a high-aspect-ratio micro
      fabricated multi-capillary column (MCC, a 50-cm-long, 450-MUm-deep, and 60-MUm
      wide four-capillary column) was fabricated by the application of the
      microelectromechanical system (MEMS) techniques. Mixtures of chemical warfare
      agent (CWA) simulants - dimethyl methylphosphonate (DMMP), triethyl phosphate
      (TEP), and methyl salicylate - were used as samples. The fabricated MCC allowed
      for the separation of all the components of the gaseous mixture within 24 s, even
      when the difference in boiling point was 4 degrees C, as in the case of TEP and
      methyl salicylate. Furthermore, interfering agents - dichloromethane, ethanol,
      and toluene - were also included in the subsequent gaseous mixture samples. The
      boiling point of these six components ranged from 78 degrees C to 219 degrees C.
      All six components were clearly separated within 70 s. This study is the first to
      report the clear separation of gas mixtures of components with close boiling
      points. The column efficiency was experimentally determined to be 12,810
      plates/m. 

PMID- 24899870
TI  - Special issue on atomically controlled fabrication technology.

PMID- 24899871
TI  - Site-selective substitutional doping with atomic precision on stepped Al (111)
      surface by single-atom manipulation.
AB  - In fabrication of nano- and quantum devices, it is sometimes critical to position
      individual dopants at certain sites precisely to obtain the specific or enhanced
      functionalities. With first-principles simulations, we propose a method for
      substitutional doping of individual atom at a certain position on a stepped metal
      surface by single-atom manipulation. A selected atom at the step of Al (111)
      surface could be extracted vertically with an Al trimer-apex tip, and then the
      dopant atom will be positioned to this site. The details of the entire process
      including potential energy curves are given, which suggests the reliability of
      the proposed single-atom doping method. 

PMID- 24899872
TI  - Phytochemistry and bioactivity of aromatic and medicinal plants from the genus
      Agastache (Lamiaceae).
AB  - Agastache is a small genus of Lamiaceae, comprising 22 species of perennial
      aromatic medicinal herbs. In this article, we review recent advances in
      phytochemical, pharmacological, biotechnological and molecular research on
      Agastache. The phytochemical profile of all Agastache species studied to date is
      generally similar, consisted of two main metabolic classes-phenylpropanoids and
      terpenoids. In the relatively variable essential oils, most populations of
      different Agastache species contain over 50 % of a phenylallyl compound
      estragole. Also, other volatile compounds (methyleugenol, pulegone, menthone,
      isomenthone and spathulenol) were reported in various proportions. Major non
      volatile metabolites belong to phenolic compounds, such as caffeic acid
      derivatives, especially rosmarinic acid as well as several flavones and flavone
      glycosides like acacetin, tilianin, agastachoside, and a rare dimeric malonyl
      flavone (agastachin). Two unique lignans-agastenol and agastinol-were also
      isolated. Terpenoids include triterpenoids of oleanane-type (maslinic acid,
      oleanolic acid and beta-amyrin), ursane-type (ursolic acid, corosolic acid and
      alpha-amyrin), and typical plant sterols, as well as abietane-type oxidized
      diterpenes (e.g., agastaquinone, agastol, and others). The bioactivity of various
      extracts or individual compounds in vitro and in vivo include antimicrobial,
      antiviral and anti-mutagenic activity, cytotoxic activity to cancer cell lines,
      and anti-nociceptive, anti-inflammatory, anti-atherogenic, antioxidant as well as
      biocidal activity to several foodstuff pests. Biotechnological and molecular
      studies have focused on in vitro propagation and enhancing the biosynthesis of
      bioactive metabolites in cell or organ cultures, as well as on the expression of
      genes involved in phenolic biosynthesis.

PMID- 24899874
TI  - Surveillance of antimicrobial resistance among clinical isolates recovered from a
      tertiary care hospital in Al Qassim, Saudi Arabia.
AB  - BACKGROUND: The emergences of antimicrobial-resistances have become an important
      issue in global healthcares. Limitations in surveying hinder the actual estimates
      of resistance in many countries. THE AIM: the present study was designed to
      retrospectically survey antimicrobial susceptibility for resistance profiling of
      dominant pathogens in a tertiary-care center in Buraidah, Saudi Arabia from
      January-2011 to December-2011. MATERIALS AND METHODS: the design was cross
      sectional and spanned records of a 1000 bacterial non-related isolates.
      Antibiograms were based on the 2012 Clinical and Laboratory Standards Institute
      guidelines. RESULTS: showed that Staphylococcus aureus, Acinetobacter baumannii,
      Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis, and
      Escherichia coli, were the most resistant. All isolates of S. aureus, S.
      epidermidis, and Staphylococcus haemolyticus, were resistant to penicillin
      (100%), and oxacillin with 52%, 75%, and 82%, respectively. Interestingly, an
      increasing trend of resistance-pattern was seen for the three species against
      gentamicin 26%, 50%, 68% ciprofloxacin 22%, 50%, 68%, tetracycline 30%, 44%, 27%,
      erythromycin 26%, 64%, 73%, and clindamycin 20%, 47%, 50% suggesting potential
      between-species transfer of resistances. Acinetobacter baumannii was resistances
      to all antibiotics tested including ciprofloxacin (90%), ceftazidime (89%),
      cefepime (67%), Trimethoprim/sulfamethoxazole (66%), amikacin (63%), gentamicin
      (51%), tetracycline (43%), piperacillin-tazobactam (42%), and imipenem (9%). A
      similar pattern was seen by P. aeruginosa. Furthermore, a typical pattern of
      resistance in K. pneumoniae carbapenemase-producing organisms was observed.
      CONCLUSION: we have shown staphylococci, Acinetobacter baumannii, Pseudomonas
      aeruginosa, and enteric bacteria were the most resistant species in this region.

PMID- 24899875
TI  - Fever of Unknown Origin in Children: A 6 year- Experience in a Tertiary Pediatric
      Egyptian Hospital.
AB  - BACKGROUND: Fever of unknown origin (FUO) is among the most conditions which
      poses challenge in diagnosis. The presence of information on regional patterns of
      FUO will shorten the time for diagnosis and reduces health services costs. There
      are almost no previous studies describing the etiology of FUO in children of
      Egypt or nearby countries. AIM OF THE STUDY: To determine different causes of FUO
      and the possible diagnostic procedures. METHODS: Data of patients with FUO,
      presented to the Infectious Diseases Unit of Mansoura University Children
      Hospital, were retrospectively collected in a 6 year-period from May 2006 to May
      2011. The study included children with a fever of 38.3 degrees  C or more
      documented by a health care provider and for which the cause could not be
      identified after 3 weeks of evaluation as an outpatient or after a week of
      evaluation in hospital. Patients were then categorized into 5 groups. RESULTS:
      127 patients met the diagnostic criteria. Infectious diseases were the commonest
      causes of FUO in 46 cases (36.22%) followed by the miscellaneous causes in 38
      cases (29.9%). Meanwhile, collagen vascular diseases and malignancy were
      diagnosed in 13 cases (10.2%) and 10 cases (7.87%) respectively. While, 20 cases
      (15.75%) remained undiagnosed. CONCLUSIONS: Infectious diseases are the commonest
      cause of FUO. The delay in diagnosis was due to atypical presentations or
      inappropriate use of antibiotic prior to the referral. Non infectious causes,
      malignancy and collagen or vascular disorders were diagnosed in rest of the
      patients. However, about 15% of our patients remained undiagnosed. The diagnosis
      was established by non-invasive means in more than two-third of the cases.

PMID- 24899873
TI  - Counter-current chromatography for the separation of terpenoids: a comprehensive
      review with respect to the solvent systems employed.
AB  - Natural products extracts are commonly highly complex mixtures of active
      compounds and consequently their purification becomes a particularly challenging
      task. The development of a purification protocol to extract a single active
      component from the many hundreds that are often present in the mixture is
      something that can take months or even years to achieve, thus it is important for
      the natural product chemist to have, at their disposal, a broad range of diverse
      purification techniques. Counter-current chromatography (CCC) is one such
      separation technique utilising two immiscible phases, one as the stationary phase
      (retained in a spinning coil by centrifugal forces) and the second as the mobile
      phase. The method benefits from a number of advantages when compared with the
      more traditional liquid-solid separation methods, such as no irreversible
      adsorption, total recovery of the injected sample, minimal tailing of peaks, low
      risk of sample denaturation, the ability to accept particulates, and a low
      solvent consumption. The selection of an appropriate two-phase solvent system is
      critical to the running of CCC since this is both the mobile and the stationary
      phase of the system. However, this is also by far the most time consuming aspect
      of the technique and the one that most inhibits its general take-up. In recent
      years, numerous natural product purifications have been published using CCC from
      almost every country across the globe. Many of these papers are devoted to
      terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide
      opportunities to discover new drugs but many of them are available at very low
      levels in nature and a huge number of them still remain unexplored. The
      collective knowledge on performing successful CCC separations of terpenoids has
      been gathered and reviewed by the authors, in order to create a comprehensive
      document that will be of great assistance in performing future purifications.

PMID- 24899876
TI  - The impact of environmental and agricultural pollutants on the prevalence of
      allergic diseases in people from Qassim, KSA.
AB  - BACKGROUND: There are multiple environmental factors that influence a sensitized
      (IgE antibody positive) patient's predisposition to manifest allergic symptoms
      following allergen exposure. The majority of allergens are known to induce
      morbidity with chronic symptoms such as rhinitis, pruritis, dermatitis and
      urticaria. AIM: To study the impact of environmental and agricultural pollutants
      with different pollens on the immunological, hematological and biochemical
      markers and to determine the prevalence of sensitization to allergens among
      exposed individuals as well as to identify the eliciting allergens. SUBJECTS AND
      METHODS: Ninety six highly exposed individuals to environmental and agricultural
      pollution in addition to 20 as controls were selected. A solid phase enzyme
      linked immunosorbent assay and the EUROLINE test kit were used for the
      quantitative determination of total IgE concentration and semi-quantitative in
      vitro assay of human IgE antibodies to some of the inhalant, ingestant and
      contactant allergens in serum samples, respectively. Percentage and absolute
      eosinophil counts and biochemical parameters were analyzed. RESULTS: Thirteen
      (13.5%) out of the 96 studied highly exposed subjects were manifesting allergic
      symptoms. Higher significant total serum IgE levels and absolute eosinophil
      counts in groups 1 and 3 of the highly exposed individuals compared to the
      control group were found (p1=0.00, p3=0.001 and p1=0.016, p3=0.028,
      respectively). Higher sensitization with inhalant Timothy grass, Aspergillus
      fumigatus, Der. Farinae and Olive; ingestant Egg yolk, Mango, Strawberry and
      Codfish and with contactant Latex/plastic and Crude oil was found in the studied
      groups compared with the controls. CONCLUSION: The present data suggest that the
      highly exposed subjects to pollution are at high risk of developing an allergy.
      For the screening of those with suspected allergen sensitization, the
      determination of specific IgE antibodies is a suitable marker of type I allergy.

PMID- 24899877
TI  - Prevailing Misconceptions of Vitiligo among Saudi School Children.
AB  - OBJECTIVES: To identify the prevailing myths and misconception about vitiligo
      among the school students in Qassim region of Saudi Arabia. METHODS: We conducted
      a cross sectional study in 18 schools of Qassim Regions in Saudi Arabia, Data was
      collected by 486 pre-tested, self-administered questionnaires. The questionnaires
      included a section on social-demographic information (age, sex, education of
      parents) besides prevailing myths on vitiligo. Data was analyzed by using SPSS
      (version 17 for Windows). RESULTS: THE RESPONSE RATE: Males 46.3%, and females
      53.3%. With vitiligo disease: 24.1% and non-diseased 75.9%, with positive family
      history: Males 9.3%, female 13.8%. Myths among students compared with gender:
      Vitiligo with; Fish/milk food (P= 0.374), calcium deficiency (P= 0.001), iron
      deficiency (P= <0.001), Vit C deficiency (P= 0.225), infectious (P= <0.001),
      Chicken pox like disease (P= <0.001), precancerous (P= 0.212) and not curable (P=
      <0.001). Myths among students compared with diseased/not diseased, namely that
      relation of vitiligo with: Fish/milk food (P= 0.006), calcium deficiency (P=
      <0.001), iron deficiency (P= 0.022), Vit C deficiency (P= <0.001), infectious (P=
      0.228), Chicken pox like disease (P= <0.001), precancerous (P= 0.051) and not
      curable (P= 0.231). CONCLUSION: The prevailing myths and conceptions delay
      seeking medical advice and should be addressed by focused health education
      programs through school health services.

PMID- 24899878
TI  - Effects of cumin extract on oxLDL, paraoxanase 1 activity, FBS, total
      cholesterol, triglycerides, HDL-C, LDL-C, Apo A1, and Apo B in in the patients
      with hypercholesterolemia.
AB  - OBJECTIVES: Paraoxanase 1 (PON1) plays a protective role against the oxidative
      modification of plasma lipoproteins and hydrolyzes lipid peroxides in human
      atherosclerotic lesions. Cumin is the dried seed of the herb Cuminumcyminum that
      is known as Zeera in Iran. Cumin seeds contain flavonoids which are now generally
      recognized to have antioxidant activity and improve the antioxidant system. So,
      they possibly modify PON1 activity and oxidized low density lipoprotein (oxLDL)
      level. The present study was aimed to evaluate the effects of cumin extract
      supplementation on oxLDL, paraoxanase 1 activity, FBS, total cholesterol,
      triglycerides, High density lipoprotein cholesterol (HDL-C), low density
      lipoprotein cholesterol (LDL-C), apolipoprotein A1 (Apo A1), and apolipoprotein B
      (Apo B)in the patients with hypercholesterolemia. METHODOLOGY: A fasting venous
      blood sample was obtained from the voluntary persons before and 45+/-3 days after
      taking cumin. Glucose, total cholesterol, and triglycerides were assayed using
      standard enzymatic procedures. HDL-Cand LDL-C were measured by direct method and
      ApoA1 and ApoB levels by immunoturbidimeteric methods. The levels of arylesterase
      and paraoxanase activities in the samples were measured by photometry methods and
      oxLDL by enzyme-linked immunosorbent assay (ELISA) method. 3 to 5 drops of cumin
      extract were added to the patient's diet three times a day based on
      manufacturer's instruction for 45+/-3 days. The biochemical parameters were
      compared before and after taking cumin. Data were analyzed using paired Student's
      t-test in SPSS statistical software (version 11.5). RESULTS: The results
      demonstrated that there was a significant decrease in the level of oxLDL after
      receiving cumin. Paraoxonase and arylesterase activities increased in serum after
      taking cumin extract. CONCLUSION: Based on the results, cumin reduces oxLDL level
      and increases both paraoxonase and arylesterase activity.

PMID- 24899879
TI  - Hypoglycemic and hypolipidemic activities of Arabic and Indian origin Salvadora
      persica root extract on diabetic rats with histopathology of their pancreas.
AB  - OBJECTIVE: To evaluate hypoglycemic and hypolipidemic effects of Salvadora
      persica aqueous extracts on streptozotocin-induced diabetic rats by measuring
      fasting blood glucose levels, lipid profiles and histopathological analysis of
      pancreas. MATERIALS AND METHODS: Experimental Diabetes was induced by single
      intraperitoneal injection of streptozotocin (60 mg/kg) to albino Wistar rats.
      Salvadora persica extracts were administered orally at 250 and 500 mg/kg dose
      levels for 21 days. Glucose tolerance test (GTT) was performed on 16 h fasted
      rats and changes in blood glucose levels, total cholesterol, triglycerides, low
      density lipoprotein (LDL), very low density lipoprotein (VLDL), high density
      lipoprotein (HDL) and histopathology of pancreas were performed. RESULTS: At a
      dose level of 500 mg/kg, blood glucose 85.25 +/- 13.20 mg/dl, total cholesterol
      (TC) 114.57 +/- 15.81(mg/dl), triglycerides (TG) 75.40 +/- 16.47(mg/dl), LDL
      42.63 +/- 13.17(mg/dl), VLDL 22.78 +/- 1.88(mg/dl), and elevation of HDL 44.88 +/
      11.61(mg/dl) were found in comparison with diabetic control on 28(th) day by
      Arabic origin Salvadora persica. It also accelerated the regeneration of beta
      cells in experimental animal's pancreas to 32.6 +/- 2.4 compared to diabetic
      control animal's pancreas of 8.1 +/- 0.5 at the end of 28(th) day. CONCLUSION:
      This study confirmed that Arabic Salvadora persica aqueous extracts at 500 mg/kg
      dose level, in comparison to other extracts (Indian Salvadora persica, 250 and
      500 mg/kg, Arabic Salvadora persica 250 mg/kg) possessed significant hypoglycemic
      and hypolipidemic activities and regenerated pancreatic beta-cells in
      streptozotocin treated diabetic rats.

PMID- 24899880
TI  - Biological functionalization of dental implants with fibronectin: a scanning
      electron microscopic study.
AB  - OBJECTIVES: Early stages of peri-implant bone formation play an essential role in
      the osseointegration and long-term success of dental implants. Biological implant
      surface coatings are an emerging technology to enhance the attachment of the
      implant to the surrounding bone and stimulate bone regeneration. The purpose of
      this study was to determine the effect of coating the implant surface with
      fibronectin on osseointegration. MATERIAL AND METHODS: The experiment was
      conducted on a total of twelve New Zealand white mature male rabbits, weight
      between 2.5-4 kg. Twenty four pure titanium implants were used in this study.
      Each rabbits received two implants, one implant in each tibia; the implant in the
      right limb was coated with fibronectin (experimental group), whilst on the
      contralateral side the implants were placed without coating (control group). Six
      rabbits were sacrificed for Scanning Electron Microscopic evaluation after 4 and
      8 week healing periods. RESULTS: The results of the present study demonstrating
      the mean gap distance between the bone and implant was greater in the control
      group compared to fibronection group at both observation periods however, the
      difference between these two groups was not statistically significant.
      CONCLUSION: Thus, it could be suggested that the biological functionalization of
      dental implants with fibronectin, may influence the integration or
      biocompatibility and bonding of the implant to the surrounding bone.

PMID- 24899881
TI  - Hepatitis B vaccination among primary health care workers in Northwest Pakistan.
AB  - BACKGROUND: We assessed hepatitis B vaccination and its determinants among health
      care workers (HCW) in rural Northwest Pakistan. METHODS: This cross sectional
      study was conducted among 485 HCWs from both public and private clinics. Data
      about hepatitis B vaccination, socio-demographic, knowledge regarding modes of
      transmission of hepatitis B virus, perceived disease severity and benefits of
      vaccination was collected through questionnaire. Multivariable logistic
      regression analysis was performed. RESULTS: Prevalence of complete hepatitis B
      vaccination was 40% (among Physicians with MBBS/MD qualification; 86% and lowest
      among non-qualified Dispensers;16%). Also, prevalence was higher among HCWs from
      public Dispensaries (77%) than those working in private clinics (35%). Being
      MBBS/MD Physician (Adj. OR 26.60; 95%CI 9.27-73.23), Non-MBBS/MD Physician
      (Adj.OR 1.89; 95%CI 0.78-4.59), qualified Dispensers (Adj. OR 3.58; 95%CI 1.34
      9.54) compared to non-qualified Dispensers, working in public clinics (Adj. OR
      2.54; 95%CI 1.13-5.69) as compared to private, perceived disease threat after
      exposure to blood and body fluids (Adj. OR 1.11; 95%CI 1.03-1.19) and perceived
      benefits of hepatitis B vaccination (Adj. OR 1.13; 95%CI 1.09-1.19) were
      significant predictors of complete hepatitis B vaccination. CONCLUSION: Improved
      perception of disease threat and benefits of vaccination and qualification of
      HCWs are associated with hepatitis B vaccination among Primary HCWs.

PMID- 24899882
TI  - Obesity in gulf countries.
AB  - Globally obesity has reached to epidemic proportions, and the people of the Gulf
      countries have also affected, especially high-income, oil-producing countries.
      The prevalence of obesity in Gulf Countries among children and adolescents ranges
      from 5% to 14% in males and from 3% to 18% in females. In adult females there is
      a significant increase of obesity with a prevalence of 2%-55% and in adult males
      1%-30% in countries of gulf region. Over the last two decades there is increased
      consumption of fast foods and sugar-dense beverages (e.g., sodas).
      Simultaneously, technological advances - cars, elevators, escalators, and remotes
      have lead to a decrease in level of activity. Traditional dependence on locally
      grown natural products such as dates, vegetables, wheat and has also shifted.
      Changes in food consumption, socioeconomic and demographic factors, physical
      activity, and urbanization are being important factors that contribute to the
      increased prevalence of obesity in the region. 

PMID- 24899884
TI  - Ventriculoperitoneal shunt with communicating peritoneal & subcutaneous
      pseudocysts formation.
AB  - A case of cerebrospinal fluid (CSF) pseudocysts in a patient with a
      ventriculoperitoneal (VP) shunt is reported to describeacute unusual location of
      developmentof pseudocyst. In the setting of a VP shunt, the frequency of
      abdominal CSF pseudocyst formation is approximately 4.5%, often being
      precipitated by a recent inflammatory/infective process or recent surgery. Larger
      pseudocysts tend to be sterile, whereas smaller or multiloculated pseudocysts are
      more often infected. Computed tomography (CT) and ultrasound (US) has
      characteristic findings. This is an uncommon presentation of VP shunt with no
      evidence of infection. The objective of this case report is to create awareness
      about imaging findings of complications of VP shunt at an unusual location. 

PMID- 24899885
TI  - Epidemic/pandemic of Cesarean delivery: the scope of the problem.

PMID- 24899883
TI  - Knee osteoarthritis related pain: a narrative review of diagnosis and treatment.
AB  - BACKGROUND: Osteoarthritis is a common progressive joint disease, involving not
      only the joint lining but also cartilage, ligaments, and bone. For the last ten
      years, majority of published review articles were not specific to osteoarthritis
      of the knee, and strength of evidence and clinical guidelines were not
      appropriately summarized. OBJECTIVES: To appraise the literature by summarizing
      the findings of current evidence and clinical guidelines on the diagnosis and
      treatment of knee osteoarthritis pain. METHODOLOGY: English journal articles that
      focused on knee osteoarthritis related pain were searched via PubMed (1 January
      2002 - 26 August 2012) and Physiotherapy Evidence Database (PEDro) databases,
      using the terms 'knee', 'osteoarthritis' and 'pain'. In addition, reference lists
      from identified articles and related book chapters were included as comprehensive
      overviews. RESULTS: For knee osteoarthritis, the highest diagnostic accuracy can
      be achieved by presence of pain and five or more clinical or laboratory criteria
      plus osteophytes. Some inconsistencies in the recommendations and findings were
      found between the clinical guidelines and systematic reviews. Generally,
      paracetamol, oral and topical non-steroidal anti-inflammatory drugs, opioids,
      corticosteroid injections and physical therapy techniques, such as therapeutic
      exercises, joint manual therapy and transcutaneous electrical nerve stimulation,
      can help reduce pain and improve function. Patient education programs and weight
      reduction for overweight patients are important to be considered. CONCLUSIONS:
      Some inconsistencies in the recommendations and findings were found between the
      clinical guidelines and systematic reviews. However, it is likely that a
      combination of pharmacological and non-pharmacological treatments is most
      effective in treating patients with knee osteoarthritis.

PMID- 24899887
TI  - Surgical decompression in acute spinal cord injury: A review of clinical
      evidence, animal model studies, and potential future directions of investigation.
AB  - The goal for treatment in acute spinal cord injury (SCI) is to reduce the extent
      of secondary damage and facilitate neurologic regeneration and functional
      recovery. Although multiple studies have investigated potential new therapies for
      the treatment of acute SCI, outcomes and management protocols aimed at
      ameliorating neurologic injury in patients remain ineffective. More recent
      clinical and basic science research have shown surgical interventions to be a
      potentially valuable modality for treatment; however, the role and timing of
      surgical decompression, in addition to the optimal surgical intervention, remain
      one of the most controversial topics pertaining to surgical treatment of acute
      SCI. As an increasing number of potential treatment modalities emerge, animal
      models are pivotal for investigating its clinical application and translation
      into human trials. This review critically appraises the available literature for
      both clinical and basic science studies to highlight the extent of investigation
      that has occurred, specific therapies considered, and potential areas for future
      research.

PMID- 24899888
TI  - Propranolol in treatment of huge and complicated infantile hemangiomas in
      egyptian children.
AB  - Background. Infantile hemangiomas (IHs) are the most common benign tumours of
      infancy. Propranolol has recently been reported to be a highly effective
      treatment for IHs. This study aimed to evaluate the efficacy and side effects of
      propranolol for treatment of complicated cases of IHs. Patients and Methods. This
      prospective clinical study included 30 children with huge or complicated IHs;
      their ages ranged from 2 months to 1 year. They were treated by oral propranolol.
      Treatment outcomes were clinically evaluated. Results. Superficial cutaneous
      hemangiomas began to respond to propranolol therapy within one to two weeks after
      the onset of treatment. The mean treatment period that was needed for the
      occurrence of complete resolution was 9.4 months. Treatment with propranolol was
      well tolerated and had few side effects. No rebound growth of the tumors was
      noted when propranolol dosing stopped except in one case. Conclusion. Propranolol
      is a promising treatment for IHs without obvious side effects. However, further
      studies with longer follow-up periods are needed. 

PMID- 24899889
TI  - A cross-sectional study of risk factors for irritable bowel syndrome in children
      8-13 years of age in suzhou, china.
AB  - To determine the prevalence and risk factors of IBS in children 8-13 years of age
      in Suzhou city, a cross-sectional study was conducted on children in grades 1
      through 6 in public elementary schools in three districts of Suzhou. A multistage
      stratified random-sampling survey was conducted in a primary investigation using
      standardized questionnaires. Rome II criteria were used to confirm IBS and their
      risk factors were analyzed. Of 8,000 questionnaires 7,472 responded
      satisfactorily for a response rate of 93.4%. IBS was diagnosed in 10.81%. A
      decrease in the prevalence of IBS was significantly associated with advancing age
      and grade in school (trend test, P < 0.05). The prevalence of IBS in females was
      higher but not significantly different than males. The significant risk factors
      for IBS included young age (OR = 0.94), food allergy (OR = 1.53), gastroenteritis
      during childhood (OR = 1.29), eating fried food (OR = 1.62), anxiety (OR = 1.49),
      psychological insults in early childhood (OR = 1.47), and parental history of
      constipation (OR = 1.81; all P < 0.05). IBS prevalence of 10.81% in study
      population warrants preventive measures such as encouraging dietary changes,
      preventing gastroenteritis and childhood psychological insults. 

PMID- 24899886
TI  - Ribonucleotide reductase metallocofactor: assembly, maintenance and inhibition.
AB  - Ribonucleotide reductase (RNR) supplies cellular deoxyribonucleotide
      triphosphates (dNTP) pools by converting ribonucleotides to the corresponding
      deoxy forms using radical-based chemistry. Eukaryotic RNR comprises alpha and
      beta subunits: alpha contains the catalytic and allosteric sites; beta houses a
      diferric-tyrosyl radical cofactor (FeIII2-Y*) that is required to initiates
      nucleotide reduction in alpha. Cells have evolved multi-layered mechanisms to
      regulate RNR level and activity in order to maintain the adequate sizes and
      ratios of their dNTP pools to ensure high-fidelity DNA replication and repair.
      The central role of RNR in nucleotide metabolism also makes it a proven target of
      chemotherapeutics. In this review, we discuss recent progress in understanding
      the function and regulation of eukaryotic RNRs, with a focus on studies revealing
      the cellular machineries involved in RNR metallocofactor biosynthesis and its
      implication in RNR-targeting therapeutics.

PMID- 24899890
TI  - Aberrant MicroRNAs in Pancreatic Cancer: Researches and Clinical Implications.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high
      rate of mortality and poor prognosis. Numerous studies have proved that microRNA
      (miRNA) may play a vital role in a wide range of malignancies, including PDAC,
      and dysregulated miRNAs, including circulating miRNAs, are associated with PDAC
      proliferation, invasion, chemosensitivity, and radiosensitivity, as well as
      prognosis. Greater understanding of the roles of miRNAs in PDAC could provide
      insights into this disease and identify potential diagnostic markers and
      therapeutic targets. The current review focuses on recent advances with respect
      to the roles of miRNAs in PDAC and their practical value. 

PMID- 24899891
TI  - Stress hyperglycemia, insulin treatment, and innate immune cells.
AB  - Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly
      altered metabolism in critical illness resulting from the release of cortisol,
      catecholamines, and cytokines, as well as glucagon and growth hormone. Recent
      studies have proposed a fundamental role of the immune system towards the
      development of insulin resistance in traumatic patients. A comprehensive review
      of published literatures on the effects of hyperglycemia and insulin on innate
      immunity in critical illness was conducted. This review explored the interaction
      between the innate immune system and trauma-induced hypermetabolism, while
      providing greater insight into unraveling the relationship between innate immune
      cells and hyperglycemia. Critical illness substantially disturbs glucose
      metabolism resulting in a state of hyperglycemia. Alterations in glucose and
      insulin regulation affect the immune function of cellular components comprising
      the innate immunity system. Innate immune system dysfunction via hyperglycemia is
      associated with a higher morbidity and mortality in critical illness. Along with
      others, we hypothesize that reduction in morbidity and mortality observed in
      patients receiving insulin treatment is partially due to its effect on the
      attenuation of the immune response. However, there still remains substantial
      controversy regarding moderate versus intensive insulin treatment. Future studies
      need to determine the integrated effects of HG and insulin on the regulation of
      innate immunity in order to provide more effective insulin treatment regimen for
      these patients. 

PMID- 24899892
TI  - Vitamin d-binding protein levels in plasma and gingival crevicular fluid of
      patients with generalized aggressive periodontitis.
AB  - Vitamin D-binding protein (DBP) is the main transport protein of vitamin D and
      plays an important role in the immune system and host defenses. The purpose of
      this study was to measure DBP levels in plasma and gingival crevicular fluid
      (GCF) of patients with generalized aggressive periodontitis (GAgP), in comparison
      to healthy controls, with the goal of elucidating the relationship between DBP
      and GAgP. Fifty-nine GAgP patients and 58 healthy controls were recruited for the
      study; clinical parameters of probing depths (PD), bleeding index, and attachment
      loss (AL) were recorded. DBP levels were measured by enzyme-linked immunosorbent
      assay. From the results, GAgP patients had higher plasma DBP concentrations (P <
      0.001) but lower GCF DBP concentrations (P < 0.001) than healthy controls. In
      GAgP group, after controlling the potential confounders of age, gender, smoking
      status, and BMI index, GCF DBP concentrations correlated negatively with PD (P <
      0.001) and AL (P = 0.009). Within the limits of the study, we concluded that
      decreased GCF DBP level and increased plasma DBP level are associated with
      periodontitis. 

PMID- 24899895
TI  - Computer-Aided Designing and Manufacturing of Lingual Fixed Orthodontic Appliance
      Using 2D/3D Registration Software and Rapid Prototyping.
AB  - The availability of 3D dental model scanning technology, combined with the
      ability to register CBCT data with digital models, has enabled the fabrication of
      orthognathic surgical CAD/CAM designed splints, customized brackets, and indirect
      bonding systems. In this study, custom lingual orthodontic appliances were
      virtually designed by merging 3D model images with lateral and posterior-anterior
      cephalograms. By exporting design information to 3D CAD software, we have
      produced a stereolithographic prototype and converted it into a cobalt-chrome
      alloy appliance as a way of combining traditional prosthetic investment and cast
      techniques. While the bonding procedure of the appliance could be reinforced, CAD
      technology simplified the fabrication process by eliminating the soldering phase.
      This report describes CAD/CAM fabrication of the complex anteroposterior lingual
      bonded retraction appliance for intrusive retraction of the maxillary anterior
      dentition. Furthermore, the CAD/CAM method eliminates the extra step of
      determining the lever arm on the lateral cephalograms and subsequent design
      modifications on the study model. 

PMID- 24899893
TI  - Paragangliomas/Pheochromocytomas: clinically oriented genetic testing.
AB  - Paragangliomas are rare neuroendocrine tumors that arise in the sympathetic or
      parasympathetic nervous system. Sympathetic paragangliomas are mainly found in
      the adrenal medulla (designated pheochromocytomas) but may also have a thoracic,
      abdominal, or pelvic localization. Parasympathetic paragangliomas are generally
      located at the head or neck. Knowledge concerning the familial forms of
      paragangliomas has greatly improved in recent years. Additionally to the genes
      involved in the classical syndromic forms: VHL gene (von Hippel-Lindau), RET gene
      (Multiple Endocrine Neoplasia type 2), and NF1 gene (Neurofibromatosis type 1),
      10 novel genes have so far been implicated in the occurrence of
      paragangliomas/pheochromocytomas: SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX,
      EGLN1, HIF2A, and KIF1B. It is currently accepted that about 35% of the
      paragangliomas cases are due to germline mutations in one of these genes.
      Furthermore, somatic mutations of RET, VHL, NF1, MAX, HIF2A, and H-RAS can also
      be detected. The identification of the mutation responsible for the
      paraganglioma/pheochromocytoma phenotype in a patient may be crucial in
      determining the treatment and allowing specific follow-up guidelines, ultimately
      leading to a better prognosis. Herein, we summarize the most relevant aspects
      regarding the genetics and clinical aspects of the syndromic and nonsyndromic
      forms of pheochromocytoma/paraganglioma aiming to provide an algorithm for
      genetic testing. 

PMID- 24899896
TI  - In vitro evaluation of leakage at implant-abutment connection of three implant
      systems having the same prosthetic interface using rhodamine B.
AB  - Objectives. Hollow space between implant and abutment may act as reservoir for
      commensal and/or pathogenic bacteria representing a potential source of tissue
      inflammation. Microbial colonization of the interfacial gap may ultimately lead
      to infection and bone resorption. Using Rhodamine B, a sensitive fluorescent
      tracer dye, we aim in this study to investigate leakage at implant-abutment
      connection of three implant systems having the same prosthetic interface.
      Materials and Methods. Twenty-one implants (seven Astra Tech, seven Euroteknika,
      and seven Dentium) with the same prosthetic interface were connected to their
      original abutments, according to the manufacturers' recommendation. After
      determination of the inner volume of each implant systems, the kinetic
      quantification of leakage was evaluated for each group using Rhodamine B (10(-2)
      M). For each group, spectrophotometric analysis was performed to detect leakage
      with a fluorescence spectrophotometer at 1 h (T0) and 48 h (T1) of incubation
      time at room temperature. Results. Astra Tech had the highest inner volume (6.8 
      MU L), compared to Dentium (4  MU L) and Euroteknika (2.9  MU L). At T0 and T1,
      respectively, the leakage volume and percentage of each system were as follows:
      Astra Tech 0.043  MU L or 1.48% (SD 0.0022), 0.08  MU L or 5.56% (SD 0.0074),
      Euroteknika 0.09  MU L or 6.93% (SD 0.0913), 0.21  MU L or 20.55% (SD 0.0035),
      and Dentium 0.07  MU L or 4.6% (SD 0.0029), 0.12  MU L or 10.47% (SD 0.0072).
      Conclusion. The tested internal conical implant-abutment connections appear to be
      unable to prevent leakage. In average, Astra Tech implants showed the highest
      inner volume and the least leakage. 

PMID- 24899894
TI  - Bariatric endocrinology: principles of medical practice.
AB  - Obesity, is a chronic, biological, preventable, and treatable disease. The
      accumulation of fat mass causes physical changes (adiposity), metabolic and
      hormonal changes due to adipose tissue dysfunction (adiposopathy), and
      psychological changes. Bariatric endocrinology was conceived from the need to
      address the neuro-endocrinological derangements that are associated with
      adiposopathy, and from the need to broaden the scope of the management of its
      complications. In addition to the well-established metabolic complications of
      overweight and obesity, adiposopathy leads to hyperinsulinemia, hyperleptinemia,
      hypoadiponectinemia, dysregulation of gut peptides including GLP-1 and ghrelin,
      the development of an inflammatory milieu, and the strong risk of vascular
      disease. Therapy for adiposopathy hinges on effectively lowering the ratio of
      orexigenic to anorexigenic signals reaching the the hypothalamus and other
      relevant brain regions, favoring a lower caloric intake. Adiposopathy, overweight
      and obesity should be treated indefinitely with the specific aims to reduce fat
      mass for the adiposity complications, and to normalize adipose tissue function
      for the adiposopathic complications. This paper defines the principles of medical
      practice in bariatric endocrinology-the treatment of overweight and obesity as
      means to treat adiposopathy and its accompanying metabolic and hormonal
      derangements. 

PMID- 24899898
TI  - Prevalence of Clinical Periodontitis and Putative Periodontal Pathogens among
      South Indian Pregnant Women.
AB  - In view of recent understanding of the association of periodontal infections and
      adverse pregnancy outcomes, the present investigation was undertaken to study the
      periodontal infections among 390 asymptomatic pregnant women and to find an
      association of bacterial etiologies with the disease. Prevalence of gingivitis
      was 38% and clinical periodontitis was 10% among the study population.
      Subgingival plaque specimens were subjected to multiplex PCR targeting ten
      putative periodontopathogenic bacteria. Among the periodontitis group, high
      detection rates of Porphyromonas gingivalis (56%), Prevotella nigrescens (44%),
      Treponema denticola (32%), and Prevotella intermedius (24%) were noted along with
      significant association with the disease (P < 0.05). 

PMID- 24899899
TI  - The prevalence of sacroiliitis and spondyloarthritis in patients with
      sarcoidosis.
AB  - Introduction. Sarcoidosis is a chronic granulomatous disease, which can involve
      different organs and systems. Coexistence of sarcoidosis and spondyloarthritis
      has been reported in numerous case reports. Purpose. To determine the prevalence
      of sacroiliitis and spondyloarthritis in patients previously diagnosed with
      sarcoidosis and to investigate any possible relation with clinical findings.
      Materials and Methods. Forty-two patients with sarcoidosis were enrolled in the
      study. Any signs and symptoms in regard to spondyloarthritis (i.e., existence of
      inflammatory back pain, gluteal pain, uveitis, enthesitis, dactylitis,
      inflammatory bowel disease, and psoriasis) were questioned in detail and
      biochemical tests were evaluated. Sacroiliac joint imaging and lateral heel
      imaging were performed in all patients. Results. Sacroiliitis was found in 6 of
      the 42 (14.3%) sarcoidosis patients and all of these patients were female. Common
      features of the disease in these six patients were inflammatory back pain as the
      major clinical complaint, stage 2 sacroiliitis as revealed by radiological
      staging, and the negativity of HLA B-27 test. These six patients with
      sacroiliitis were diagnosed with spondyloarthritis according to the criteria of
      ASAS and of ESSG. Conclusion. We found spondyloarthritis in patients with
      sarcoidosis at a higher percentage rate than in the general population (1-1.9%).
      Controlled trials involving large series of patients are required for the
      confirmation of the data. 

PMID- 24899900
TI  - Differential expression of placental glucocorticoid receptors and growth arrest
      specific transcript 5 in term and preterm pregnancies: evidence for involvement
      of maternal stress.
AB  - Pregnancy-specific stress predicts birth outcomes. We hypothesized that there is
      a maternal stress-GR interaction that can influence fetal birth weight. This
      study examined the relationship between mothers' stress and attitude towards
      their pregnancies, placental glucocorticoid receptors (GRs) and growth arrest
      specific transcript 5 (GAS5) expression, and the status of GR polymorphism, with
      their infants' birth weights. GAS5 and GR alpha were the predominant transcripts
      in both term and preterm placentas, with GAS5 being primarily localized in the
      syncytiotrophoblasts. In an attempt to mimic moderate and high stress environment
      in vitro, BeWo and JEG-3 cytotrophoblast cell lines were treated with 10 nM-1000
      nM cortisol. Only expression of GAS5 was significantly upregulated by cortisol in
      all treatments compared with basal levels, but none of the GRs changed expression
      significantly. In an attempt to assess a stress versus gene interaction, we
      studied four GR polymorphisms. In the homozygous group for Tth111I polymorphism,
      mothers with negative attitudes towards the pregnancy gave birth to infants with
      significantly lower birth weights compared to women with positive/neutral
      attitudes. None of the GR splice variants were associated with maternal stress.
      However, placental GAS5 levels were inversely correlated with maternal stress.
      This study points towards a potential gene-environment interaction that could be
      of predictive value for fetal weight. 

PMID- 24899901
TI  - Reporting a rare case of pleomorphic adenoma of the breast.
AB  - Pleomorphic adenoma (PA) is the most common tumor type in the salivary gland. PA
      is uncommon in the breast tissue. Only 73 cases of PA of the breast have been
      reported in the world literature. We are reporting the 74th case of PA of the
      breast. A 61-year-old woman was referred to Shahid Beheshti Hospital Obstetric
      Clinic with bloody painless discharge from the right nipple. A bean size mass was
      detected immediately below the right nipple. After an excisional biopsy, the
      pathologist found proliferation in epithelial and myoepithelial cells that had
      small and multiple nuclei, myxoid and chondroid stroma. Immunohistochemistry
      stain was positive for S-100 and patchy for GFAP in tumor cells and for SMA
      around the tubule-glandular and tumor cell aggregates and suggested PA of the
      breast. It is essential for the pathologists to consider PA of the breast as a
      differential diagnosis of a rounded circumscribed mass in the juxta-areolar
      areas. Careful paraffin sections should be performed to avoid an unnecessary
      mastectomy. 

PMID- 24899902
TI  - Esophageal rupture as a primary manifestation in eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a chronic inflammatory process characterized by
      symptoms of esophageal dysfunction and, histologically, by eosinophilic
      infiltration of the esophagus. In adults, it commonly presents with dysphagia,
      food impaction, and chest or abdominal pain. Chronic inflammation can lead to
      diffuse narrowing of the esophageal lumen which may cause food impaction.
      Endoscopic procedures to relieve food impaction may lead to complications such as
      esophageal perforation due to the friability of the esophageal mucosa.
      Spontaneous transmural esophageal rupture, also known as Boerhaave's syndrome, as
      a primary manifestation of EoE is rare. In this paper, we present two adult
      patients who presented with esophageal perforation as the initial manifestation
      of EoE. This rare complication of EoE has been documented in 13 other reports (11
      adults, 2 children) and only 1 of the patients had been previously diagnosed with
      EoE. A history of dysphagia was present in 1 of our patients and in the majority
      of previously documented patients. Esophageal perforation is a potentially severe
      complication of EoE. Patients with a history of dysphagia and patients with
      spontaneous esophageal perforation should warrant an evaluation for EoE. 

PMID- 24899897
TI  - RNA Viruses: ROS-Mediated Cell Death.
AB  - Reactive oxygen species (ROS) are well known for being both beneficial and
      deleterious. The main thrust of this review is to investigate the role of ROS in
      ribonucleic acid (RNA) virus pathogenesis. Much evidences has accumulated over
      the past decade, suggesting that patients infected with RNA viruses are under
      chronic oxidative stress. Changes to the body's antioxidant defense system, in
      relation to SOD, ascorbic acid, selenium, carotenoids, and glutathione, have been
      reported in various tissues of RNA-virus infected patients. This review focuses
      on RNA viruses and retroviruses, giving particular attention to the human
      influenza virus, Hepatitis c virus (HCV), human immunodeficiency virus (HIV), and
      the aquatic Betanodavirus. Oxidative stress via RNA virus infections can
      contribute to several aspects of viral disease pathogenesis including apoptosis,
      loss of immune function, viral replication, inflammatory response, and loss of
      body weight. We focus on how ROS production is correlated with host cell death.
      Moreover, ROS may play an important role as a signal molecule in the regulation
      of viral replication and organelle function, potentially providing new insights
      in the prevention and treatment of RNA viruses and retrovirus infections. 

PMID- 24899903
TI  - Contaminated pond water favors cholera outbreak at haibatpur village, purba
      medinipur district, west bengal, India.
AB  - Health workers reported an increased number of diarrhea cases at Haibatpur
      village on June 17, 2012. This outbreak was investigated with the following
      objectives: to confirm the existence of diarrhea outbreak, to find out the risk
      factors, and propose control measures. Cases were listed; spot map and epidemic
      curve were drawn. Attack rate was calculated by age and sex and risk factors were
      found out by calculating odds ratio (OR) with 95% confidence interval (CI).
      Rectal swabs were taken and water specimens were collected for laboratory test.
      Forty-one cases of patients were identified with overall attack rate (AR) was 5%
      (41/780). AR among men was higher 6% (25/404) than women. There was no death. V.
      cholerae 01 Eltor Ogawa was isolated from one (1/4) stool specimen. Spot map
      showed cases clustered around two ponds which were contaminated with coliform
      organisms. The underground water was a bit saline in nature. Using pond water for
      preparation of fermented rice (Panta Bhat) (OR 4.73, 95% CI 1.69-13.51), washing
      utensil in pond water (OR 7.31, 95% CI 1.77-42.29) were associated with cholera
      outbreak. Health education was done to villagers. Disinfection of two ponds with
      bleaching powder was done. We proposed supplying of safe drinking water and
      repairing defective deep tube well to village. 

PMID- 24899904
TI  - Lipid profile and correlation to cardiac risk factors and cardiovascular function
      in type 1 adolescent diabetics from a developing country.
AB  - Objective. The adverse role of dyslipidemia in predicting cardiovascular outcomes
      has not been elucidated extensively among type 1 diabetics in the literature.
      Methods. We assessed dyslipidemia and its correlation to other cardiac risk
      factors in adolescents with type 1 diabetes. Total thirty type 1 adolescent
      diabetics were evaluated for their metabolic profile, including serum lipids and
      echocardiography was performed. Results. The average age of the cohort was 14.3
      +/- 3.09 yr with disease duration of 5.35 +/- 2.94 yr. The mean HbA1C was 8.01%.
      The mean serum cholesterol, LDL, HDL, and triglyceride were normal. Serum
      cholesterol was high in patients with longer disease duration (P = 0.011, r =
      0.41), high systolic blood pressure (P = 0.04, r = 0.32), and elevated HbA1C > 8%
      (P = 0.038, r = 0.33). Higher lipid values were associated with poorer carotid
      artery distensibility (P > 0.05) and higher carotid artery intimomedial thickness
      (cIMT) (P < 0.05 for cholesterol and LDL). Hyperglycemia adversely affected
      ejection fractions, though serum lipids did not show any significant effect on
      left ventricular parameters. Conclusions. Dyslipidemia and hyperglycemia can
      serve as biomarkers for cardiovascular dysfunction in at-risk adolescents with
      type 1 diabetes. Carotid artery parameters are adjunctive tools which may be
      affected early in the course of macrovascular disease. 

PMID- 24899905
TI  - Early childhood nutritional status in CARICOM countries: an overview with respect
      to five nutrition related millennium development goals.
AB  - Previous reviews of nutritional status in children under 5 years describe the
      Caribbean grouped with Latin America. This paper focuses specifically on the
      Caribbean and the goals and targets of the Millennium Declaration that have
      bearing on childhood development. The results indicate that CARICOM countries
      have made progress in terms of child health as assessed by gross health
      indicators. Yet, the millennium generation experiences coexistence of
      undernutrition and overweight in early childhood. The associations of GNI with
      markers such as poverty indices are somewhat inconsistent with traditional
      findings and highlight a need to reassess the causes of infant mortality and low
      birth weight. However, a lack of systematic local data has hampered progress on
      an individual country basis. Interventions that deal more pointedly with country
      specific needs are required including those targeting obesity if the MDGs are to
      be attained by all member states. 

PMID- 24899906
TI  - Effect of regular yogic training on growth hormone and dehydroepiandrosterone
      sulfate as an endocrine marker of aging.
AB  - Growth hormone (GH) and dehydroepiandrosterone sulfate (DHEAS) secretion decline
      with advancing age and are associated with the symptoms of aging. Yogic texts
      claimed that regular practice of yoga may restore and maintain general
      endocrinological properties in the human body. Objective of the Study. To observe
      the effect of yogic training for twelve weeks on basal level of GH and DHEAS in
      middle aged group. Method. Forty-five untrained volunteers were divided into two
      groups, that is, yoga practicing (experimental: male 15, age 42.80 +/- 7.43 yrs;
      female 8, age 44.75 +/- 8.40 yrs) and waitlisted control group (male 15, age
      41.67 +/- 7.87 yrs; female 7, age 45.43 +/- 7.00 yrs). The experimental group
      underwent combined yogic practices daily in the morning for 6 days/week for 12
      weeks, whereas control group continued their usual routine activities. Standing
      height, body weight, body mass index, and basal level of GH and DHEAS were
      measured before commencement and after six and twelve weeks of yogic training
      period. The repeated measure ANOVA was used for data analysis. Results. 12 weeks
      of yogic training produces a significant increase in GH and DHEAS for both male
      and female groups as compared to their baseline data, whereas no as such changes
      were observed in the control group. Conclusion. Combined approach of graded yogic
      training may be beneficial for maintaining the basal level of GH and DHEAS in the
      human body, thus promoting healthy aging. 

PMID- 24899907
TI  - Ligand-based and structure-based investigation for Alzheimer's disease from
      traditional chinese medicine.
AB  - Alzheimer's disease is a neurodegenerative disease that was conventionally
      thought to be related to the sedimentation of beta-amyloids, but drugs designed
      according to this hypothesis have generally failed. That FKBP52 can reduce the
      accumulation of tau proteins, and that Tacrolimus can reduce the pathological
      changes of tau proteins are new directions away from the long held amyloid-beta
      centric concept. Therefore, the screening of traditional Chinese medicine
      compounds for those with higher affinity towards FKBP52 than Tacrolimus may be a
      new direction for treating Alzheimer's disease. This study utilizes ligand-based
      and structure-based methods as the foundation. By utilizing dock scores and the
      predicted pIC50 from SVM, MLR, and Bayesian Network, several TCM compounds were
      selected for further analysis of their protein-ligand interactions. Daphnetoxin
      has higher affinity and complex structure stability than Tacrolimus; Lythrancine
      II exhibits the most identical trends in FKBP52 interactions as Tacrolimus, and
      20-O-(2'E,4'E-decadienoyl)ingenol may be further modified at its hydrocarbon
      chain to promote interaction with FKBP52. In addition, we observed the residue
      Tyr113 of FKBP52 may play a key role in protein-ligand interaction. Our results
      indicate that Daphnetoxin, 20-O-(2'E,4'E-decadienoyl)ingenol, and Lythrancine II
      may be starting points for further modification as a new type of non-amyloid-beta
      centric drug for Alzheimer's disease. 

PMID- 24899908
TI  - In Silico Investigation of Cytochrome P450 2C9 in relation to Aging Using
      Traditional Chinese Medicine.
AB  - Cytochrome P450 2C9 (CYP2C9) metabolizes dehydroepiandrosterone-sulfate (DHEA-S),
      but in elderly people the amount of DHEA-S remaining after CYP2C9 metabolization
      may be insufficient for optimal health. A prediction model, molecular docking,
      and molecular dynamics were used to screen the Traditional Chinese Medicine (TCM)
      database to determine molecular compounds that may inhibit CYP2C9. The candidate
      compounds apocynoside(I), 4-methoxymagndialdehyde, and prunasin have higher Dock
      Scores, and prediction bioactivity than warfarin (the control drug). The
      interaction between 4-methoxymagndialdehyde and CYP2C9 is more intense than with
      other TCM compounds, but the simulation is longer. In these compounds,
      apocynoside(I) and prunasin have a greater number of pathways for their flexible
      structure, but these structures create weak interactions. These candidate
      compounds, which are known to have antioxidation and hypolipidemic functions that
      have an indirect effect on the aging process, can be extracted from traditional
      Chinese medicines. Thus, these candidate compounds may become CYP2C9 inhibitors
      and play an important role in providing optimal health in the elderly. 

PMID- 24899910
TI  - Acupuncture effect and omics studies.

PMID- 24899909
TI  - In Silico Insight into Potent of Anthocyanin Regulation of FKBP52 to Prevent
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is caused by the hyperphosphorylation of Tau protein
      aggregation. FKBP52 (FK506 binding protein 52) has been found to inhibit Tau
      protein aggregation. This study found six different kinds of anthocyanins that
      have high binding potential. After analyzing the docking positions, hydrophobic
      interactions, and hydrogen bond interactions, several amino acids were identified
      that play important roles in protein and ligand interaction. The proteins'
      variation is described using eigenvectors and the distance between the amino
      acids during a molecular dynamics simulation (MD). This study investigates the
      three loops based around Glu85, Tyr113, and Lys121-all of which are important in
      inducing FKBP52 activation. By performing a molecular dynamic simulation process
      between unbound proteins and the protein complex with FK506, it was found that
      ligand targets that docked onto the FK1 domain will decrease the distance between
      Glu85/Tyr113 and Glu85/Lys121. The FKBP52 structure variation may induce FKBP52
      activation and inhibit Tau protein aggregation. The results indicate that
      anthocyanins might change the conformation of FKBP52 during binding. In addition,
      the purple anthocyanins, such as cyanidin-3-glucoside and malvidin-3-glucoside,
      might be better than FK506 in regulating FKBP52 and treating Alzheimer's disease.

PMID- 24899911
TI  - Pharmacopuncture for cancer care: a systematic review.
AB  - Background. Pharmacopuncture, injection to acupoints with pharmacological
      medication or herbal medicine, is a new acupuncture therapy widely available in
      Korea and China for cancer-related symptoms. However, the evidence is yet to be
      clear. Objective. To determine pharmacopuncture's effectiveness on cancer-related
      symptoms. Methods. Eleven databases were searched for randomized controlled
      trials of pharmacopuncture in cancer patients. The Cochrane risk of bias (ROB)
      assessment tool was used for quality assessment. Results. Twenty-two studies
      involving 2,459 patients were included. Five trials of chemotherapy-induced
      nausea and vomiting (CINV) underwent meta-analysis. Pharmacopuncture
      significantly relieved severity of CINV compared with control group (3 trials,
      risk ratio (RR) 1.28, 95% confidence interval (CI) = 1.14-1.44). The frequency of
      CINV was also significantly reduced with pharmacopuncture (2 trials, RR 2.47, 95%
      CI = 2.12-2.89). Seventeen trials studied various symptoms, and in most studies,
      pharmacopuncture significantly relieved pain, ileus, hiccup, fever, and
      gastrointestinal symptoms and improved quality of life in various cancer
      patients. ROB was generally high. Conclusion. It may be suggested with caution
      that pharmacopuncture may help various symptom relief in cancer patients, but it
      is hard to draw a firm conclusion due to clinical heterogeneity and high ROB of
      the included studies, hence warranting further investigation. 

PMID- 24899912
TI  - Acupuncture for treating whiplash associated disorder: a systematic review of
      randomised clinical trials.
AB  - The aim of this systematic review was to determine the effectiveness of
      acupuncture for the treatment of whiplash associated disorder (WAD). Twenty
      databases were searched from their inceptions to Oct. 2013. Randomised clinical
      trials (RCTs) of acupuncture (AT), electroacupuncture (EA), or dry needling (DN)
      for the treatment of WAD were considered eligible. The risk of bias was assessed
      using the Cochrane tool. Six RCTs met the inclusion criteria. Most of the
      included RCTs have serious methodological flaws. Four of the RCTs showed
      effectiveness of AT, AT in addition to usual care (UC), AT in addition to herbal
      medicine (HM) or EA was more effective than relaxation, sham EA, sham EA in
      addition to HM or UC for conditioned pain modulation (CPM) and alleviating pain.
      In one RCT, DN in addition to physiotherapy (PT) had no effect compared to sham
      DN in addition to PT for the reduction of pain. None of the RCTs showed that
      AT/EA/DN was more effective than various types of control groups in reducing
      disability/function. One RCT did not report between-group comparisons of any
      outcome measures. The evidence for the effectiveness of AT/EA/DN for the
      treatment of WAD is limited. Therefore, more research in this area is warranted. 

PMID- 24899914
TI  - Multiple human pressures and their spatial patterns in European running waters.
AB  - Running water ecosystems of Europe are affected by various human pressures.
      However, little is known about the prevalence, spatial patterns, interactions
      with natural environment and co-occurrence of pressures. This study represents
      the first high-resolution data analysis of human pressures at the European scale,
      where important pressure criteria for 9330 sampling sites in 14 European
      countries were analysed. We identified 15 criteria describing major anthropogenic
      degradation and combined these into a global pressure index by taking additive
      effects of multiple pressures into account. Rivers are affected by alterations of
      water quality (59%), hydrology (41%) and morphology (38%). Connectivity is
      disrupted at the catchment level in 85% and 35% at the river segment level.
      Approximately 31% of all sites are affected by one, 29% by two, 28% by three and
      12% by four pressure groups; only 21% are unaffected. In total, 47% of the sites
      are multi-impacted. Approximately 90% of lowland rivers are impacted by a
      combination of all four pressure groups.

PMID- 24899913
TI  - In silico design for adenosine monophosphate-activated protein kinase agonist
      from traditional chinese medicine for treatment of metabolic syndromes.
AB  - Adenosine monophosphate-activated protein kinase (AMPK) acts as a master mediator
      of metabolic homeostasis. It is considered as a significant millstone to treat
      metabolic syndromes including obesity, diabetes, and fatty liver. It can sense
      cellular energy or nutrient status by switching on the catabolic pathways.
      Investigation of AMPK has new findings recently. AMPK can inhibit cell growth by
      the way of autophagy. Thus AMPK has become a hot target for small molecular drug
      design of tumor inhibition. Activation of AMPK must undergo certain extent change
      of the structure. Through the methods of structure-based virtual screening and
      molecular dynamics simulation, we attempted to find out appropriate small
      compounds from the world's largest TCM Database@Taiwan that had the ability to
      activate the function of AMPK. Finally, we found that two TCM compounds,
      eugenyl_beta-D-glucopyranoside and 6-O-cinnamoyl-D-glucopyranose, had the
      qualification to be AMPK agonist. 

PMID- 24899915
TI  - Impact of dose and sensitivity heterogeneity on TCP.
AB  - This present paper presents an analytical description and numerical simulations
      of the influence of macroscopic intercell dose variations and intercell
      sensitivity variations on the probability of controlling the tumour. Computer
      simulations of tumour control probability accounting for heterogeneity in dose
      and radiation sensitivity were performed. An analytical expression for tumor
      control probability accounting for heterogeneity in sensitivity was also proposed
      and validated against simulations. The results show good agreement between
      numerical simulations and the calculated TCP using the proposed analytical
      expression for the case of a heterogeneous dose and sensitivity distributions.
      When the intratumour variations of dose and sensitivity are taken into account,
      the total dose required for achieving the same level of control as for the case
      of homogeneous distribution is only slightly higher, the influence of the
      variations in the two factors taken into account being additive. The results of
      this study show that the interplay between cell or tumour variation in the
      sensitivity to radiation and the inherent heterogeneity in dose distribution is
      highly complex and therefore should be taken into account when predicting the
      outcome of a given treatment in terms of tumor control probability. 

PMID- 24899916
TI  - DV-curve representation of protein sequences and its application.
AB  - Based on the detailed hydrophobic-hydrophilic(HP) model of amino acids, we
      propose dual-vector curve (DV-curve) representation of protein sequences, which
      uses two vectors to represent one alphabet of protein sequences. This graphical
      representation not only avoids degeneracy, but also has good visualization no
      matter how long these sequences are, and can reflect the length of protein
      sequence. Then we transform the 2D-graphical representation into a numerical
      characterization that can facilitate quantitative comparison of protein
      sequences. The utility of this approach is illustrated by two examples: one is
      similarity/dissimilarity comparison among different ND6 protein sequences based
      on their DV-curve figures the other is the phylogenetic analysis among
      coronaviruses based on their spike proteins. 

PMID- 24899917
TI  - Dynamics of posttranslational modifications of p53.
AB  - The latest experimental evidence indicates that acetylation of p53 at K164
      (lysine 164) and K120 may induce directly cell apoptosis under severe DNA damage.
      However, previous cell apoptosis models only studied the effects of active and/or
      inactive p53, that is, phosphorylation/dephosphorylation of p53. In the present
      paper, based partly on Geva-Zatorsky et al. (2006) and Batchelor et al. (2008),
      we propose a new cell apoptosis network, in which p53 has three statuses, that
      is, unphosphorylated p53, phosphorylated p53, and acetylated p53. The time delay
      differential equations (DDEs) are formulated based on our network to investigate
      the dynamical insights of p53-induced cell apoptosis. In agreement with
      experiments (Loewer et al. (2010)), our simulations indicate that acetylated p53
      accumulates gradually and then induces the proapoptotic protein Bax under enough
      DNA damage. Moreover, phosphorylated p53 oscillates and initiates cell repair
      during DNA damage. 

PMID- 24899918
TI  - Ranking biomedical annotations with annotator's semantic relevancy.
AB  - Biomedical annotation is a common and affective artifact for researchers to
      discuss, show opinion, and share discoveries. It becomes increasing popular in
      many online research communities, and implies much useful information. Ranking
      biomedical annotations is a critical problem for data user to efficiently get
      information. As the annotator's knowledge about the annotated entity normally
      determines quality of the annotations, we evaluate the knowledge, that is,
      semantic relationship between them, in two ways. The first is extracting
      relational information from credible websites by mining association rules between
      an annotator and a biomedical entity. The second way is frequent pattern mining
      from historical annotations, which reveals common features of biomedical entities
      that an annotator can annotate with high quality. We propose a weighted and
      concept-extended RDF model to represent an annotator, a biomedical entity, and
      their background attributes and merge information from the two ways as the
      context of an annotator. Based on that, we present a method to rank the
      annotations by evaluating their correctness according to user's vote and the
      semantic relevancy between the annotator and the annotated entity. The
      experimental results show that the approach is applicable and efficient even when
      data set is large. 

PMID- 24899920
TI  - Multi-morbidity and disability, findings from the KORA-Age study.

PMID- 24899922
TI  - A life course approach to physical capability: findings from the HALCyon research
      programme.

PMID- 24899921
TI  - Collaborative Research on Ageing in Europe project's aims and main results.

PMID- 24899923
TI  - Major drivers of health inequalities in later life and future research needs.

PMID- 24899919
TI  - Identification of crucial parameters in a mathematical multiscale model of
      glioblastoma growth.
AB  - Glioblastomas are highly malignant brain tumours. Mathematical models and their
      analysis provide a tool to support the understanding of the development of these
      tumours as well as the design of more effective treatment strategies. We have
      previously developed a multiscale model of glioblastoma progression that covers
      processes on the cellular and molecular scale. Here, we present a novel nutrient
      dependent multiscale sensitivity analysis of this model that helps to identify
      those reaction parameters of the molecular interaction network that influence the
      tumour progression on the cellular scale the most. In particular, those
      parameters are identified that essentially determine tumour expansion and could
      be therefore used as potential therapy targets. As indicators for the success of
      a potential therapy target, a deceleration of the tumour expansion and a
      reduction of the tumour volume are employed. From the results, it can be
      concluded that no single parameter variation results in a less aggressive tumour.
      However, it can be shown that a few combined perturbations of two systematically
      selected parameters cause a slow-down of the tumour expansion velocity
      accompanied with a decrease of the tumour volume. Those parameters are primarily
      linked to the reactions that involve the microRNA-451 and the thereof regulated
      protein MO25. 

PMID- 24899924
TI  - Health trends and health indicators.

PMID- 24899925
TI  - Development of a standardised instrument to assess ageing-related health outcomes
      in a comparable fashion in European ageing populations, the CHANCES Health
      Module.

PMID- 24899926
TI  - The English Longitudinal Study of Ageing (ELSA): Depressive symptoms and physical
      performance.

PMID- 24899927
TI  - Epidemiological approaches to frailty - contributions from the ESTHER study.

PMID- 24899928
TI  - Emotion and Morality in Psychopathy and Paraphilias.
AB  - Understanding the role of emotion in moral judgment has been an active area of
      investigation and debate. Here we comment on this topic by examining the
      interaction between emotion and moral judgment in certain psychopathological
      groups that are characterized by abnormalities in emotion processing, such as
      psychopaths and sexual offenders with paraphilic disorders.

PMID- 24899929
TI  - Nursing home-acquired pneumonia: course and management in the emergency
      department.
AB  - BACKGROUND: Pneumonia is among the foremost causes of hospitalization and
      mortality in patients residing in extended care facilities. Despite its
      prevalence, there is currently little literature focusing on the course and
      management of nursing home-acquired pneumonia (NHAP) in the emergency department
      (ED). Our objective was to investigate the ED presentation, course, management
      and outcomes in patients admitted through the ED with NHAP. METHODS: A
      retrospective chart review of nursing home patients with a presumptive or final
      diagnosis of pneumonia admitted through the ED was performed at two large
      hospitals in Detroit, Michigan. RESULTS: A total of 296 patients were included in
      the study from 2002 to 2007 with a mean age of 81.1 years (SD +/- 10.95) and
      55.4% females. Blood cultures were performed on 90.8% of patients in the ED;
      17.8% of these revealed growths, but half of these were considered contaminants.
      Initial chest x-ray in the ED was read as possible pneumonia in 18.2% of
      patients; 73.9% were started on antibiotics (ABX) in the ED. Mean hospital length
      of stay (LOS) was 10.75 days (SD +/- 9.35) and in-hospital mortality was 16.2%.
      Time until first ABX in univariate analysis was nearly significant (p = 0.053)
      for mortality prediction, and the appropriate versus inappropriate ABX (per the
      Infectious Diseases Society of America and American Thoracic Society guidelines)
      did not affect mortality. Patients treated with a single ABX had significantly
      increased LOS (p = 0.0089). There was poor correlation between LOS and time until
      first ABX as well as LOS and time until appropriate ABX with a correlation
      coefficient of -0.048 (p = 0.42) and -0.08 (p = 0.43), respectively. CONCLUSIONS:
      In this data set of NHAP patients admitted through the ED, we found a
      surprisingly low prevalence of true-positive blood cultures, high incidence of
      antibiotic pre-treatment at nursing homes prior to admission, high hospital
      mortality and low immunization rates. There was a wide spectrum of pathogens
      grown in blood culture. Only two thirds of the patients had dyspnea at
      presentation, and less than half had either cough or fever. On physical
      examination, about one fourth had no clinical findings consistent with pneumonia.
      Further, less than one fifth of chest x-rays were interpreted as possible
      pneumonia.

PMID- 24899931
TI  - Message from the president of the korean society of nuclear medicine.

PMID- 24899930
TI  - On Launching a New Twenty-first Century Quarterly Journal, Nuclear Medicine and
      Molecular Imaging.

PMID- 24899932
TI  - Sodium iodide symporter and the radioiodine treatment of thyroid carcinoma.
AB  - Since the specific accumulation of iodide in thyroid was found in 1915,
      radioiodine has been widely applied to diagnose and treat thyroid cancer. Iodide
      uptake occurs across the membrane of the thyroid follicular cells and cancer
      cells through an active transporter process mediated by the sodium iodide
      symporter (NIS). The NIS coding genes were cloned and identified from rat and
      human in 1996. Evaluation of the NIS gene and protein expression is critical in
      the management of thyroid cancer, and several approaches have been tried to
      increase NIS levels. Identification of the NIS gene has provided a means of
      expanding its role in the radionuclide gene therapy of nonthyroidal cancers as
      well as thyroid cancer. In this article, we explain the relationship between NIS
      expression and the treatment of thyroid carcinoma with I-131, and we include a
      review of the results of our experimental and clinical trials. 

PMID- 24899934
TI  - Recent Trends in the Nucleophilic [(18)F]-radiolabeling Method with No-carrier
      added [(18)F]fluoride.
AB  - Noninvasive imaging in living subjects with positron emission tomography (PET)
      provides early detection of diseases in humans. For this application, it is
      necessary to prepare specific molecular imaging probes labeled with positron
      emitting radioisotopes such as fluorine-18 for obtaining high-quality PET
      imaging. In this review, we describe recent trends in the F-18 radiolabeling
      method for the introduction of no-carrier-added fluorine-18, which was obtained
      from an (18)O(p,n)(18)F reaction, into a specific molecular site, which in turn
      is intended to serve as an imaging agent for PET study. These labeling protocols
      are based on ionic liquid media (18)F radiofluorination in the presence of some
      water, enzymatic (18)F fluorination using fluorinase in water solution, non-polar
      protic alcohol media (18)F radiofluorination and its mechanism, and nucleophilic
      (18)F fluorination of an aromatic iodonium salt precursor. 

PMID- 24899933
TI  - Molecular imaging of biological gene delivery vehicles for targeted cancer
      therapy: beyond viral vectors.
AB  - Cancer persists as one of the most devastating diseases in the world. Problems
      including metastasis and tumor resistance to chemotherapy and radiotherapy have
      seriously limited the therapeutic effects of present clinical treatments. To
      overcome these limitations, cancer gene therapy has been developed over the last
      two decades for a broad spectrum of applications, from gene replacement and
      knockdown to vaccination, each with different requirements for gene delivery. So
      far, a number of genes and delivery vectors have been investigated, and
      significant progress has been made with several gene therapy modalities in
      clinical trials. Viral vectors and synthetic liposomes have emerged as the
      vehicles of choice for many applications. However, both have limitations and
      risks that restrict gene therapy applications, including the complexity of
      production, limited packaging capacity, and unfavorable immunological features.
      While continuing to improve these vectors, it is important to investigate other
      options, particularly nonviral biological agents such as bacteria,
      bacteriophages, and bacteria-like particles. Recently, many molecular imaging
      techniques for safe, repeated, and high-resolution in vivo imaging of gene
      expression have been employed to assess vector-mediated gene expression in living
      subjects. In this review, molecular imaging techniques for monitoring biological
      gene delivery vehicles are described, and the specific use of these methods at
      different steps is illustrated. Linking molecular imaging to gene therapy will
      eventually help to develop novel gene delivery vehicles for preclinical study and
      support the development of future human applications. 

PMID- 24899935
TI  - Comparison between (18)F-FDG PET/CT and EMG Mapping for Identifying Dystonic
      Superficial Muscles in Primary Cervical Dystonia: Preliminary Results.
AB  - PURPOSE: This study was conducted to compare (18)F-FDG PET/CT and
      electromyography (EMG) mapping in patients with primary cervical dystonia (PCD)
      to find dystonic superficial cervical muscles. METHODS: Ten consecutive patients
      with PCD (M:F = 5:5, age 44 +/- 13 years) whose dystonic posture was not relieved
      with conventional muscle relaxant therapy were included. Target cervical muscles
      for the comparison between (18)F-FDG PET/CT and EMG mapping were four
      representative superficial bilateral cervical muscles: splenius capitis muscle,
      sternocleidomstoid muscle, upper trapezius muscle, and leavator scapulae muscle.
      The diagnostic efficacy was compared between (18)F-FDG PET/CT and EMG mapping
      using physical exam and measurement of rotation angle as the gold standard.
      RESULTS: Among 80 muscles evaluated, there were 21 (26%) dystonic superficial
      cervical muscles assessed with physical exam and motion analysis. The
      sensitivity, specificity, and accuracy for localizing dystonic muscles were 76,
      92, and 88% for (18)F-FDG PET/CT, and 95, 66, and 74% for EMG mapping,
      respectively. The sensitivity of EMG mapping was significantly higher than that
      of (18)F-FDG PET/CT. In contrast, (18)F-FDG PET/CT was significantly superior to
      EMG mapping for specificity and accuracy. CONCLUSIONS: (18)F-FDG PET/CT is more
      specific and accurate than EMG mapping for finding superficial dystonic cervical
      muscles. The high sensitivity of EMG mapping suggests that (18)F-FDG PET/CT and
      EMG mapping are complementary for finding dystonic superficial cervical muscles.

PMID- 24899936
TI  - Tumor Burden Assessed by the Maximum Standardized Uptake Value and Greatest
      Diameter on FDG-PET Predicts Prognosis in Untreated Diffuse Large B-cell
      Lymphoma.
AB  - PURPOSE: It is uncertain whether the tumor burden as assessed using FDG-PET has
      prognostic significance in newly diagnosed diffuse large B-cell lymphoma (DLBCL).
      The authors undertook this study to determine whether a parameter that reflects
      both FDG uptake magnitude and the greatest tumor diameter is a prognostic
      indicator in DLBCL. MATERIALS AND METHODS: Forty-two DLBCL patients (age, 57.4 +/
      15.5 years; male/female = 25/17; stage I/II/III/IV=5/17/10/10) who underwent FDG
      PET before chemotherapy were enrolled. A lesion with the highest maximum
      standardized uptake value (MaxSUV) on the PET image was selected, and size
      incorporated MaxSUV (SIMaxSUV) of mass was calculated as MaxSUV * greatest
      diameter (mm) on the transaxial PET image. Median follow-up duration was 20.0
      months. RESULTS: Twelve (28.6% = 12/42) patients experienced disease progression,
      and 10 (23.8% = 10/42) died during follow-up. Among six variables [Ann Arbor
      stage, %Ki-67 expression, International Prognostic Index (IPI), MaxSUV, greatest
      diameter, and SIMaxSUV] investigated, only SIMaxSUV was found to be a single
      determinant of progression-free and overall survivals by multivariate analyses (p
      < 0.05). CONCLUSION: These results suggest that SIMaxSUV, a new FDG-PET parameter
      that incorporates FDG uptake magnitude and the greatest tumor diameter, may be a
      useful indicator of prognosis in untreated DLBCL.

PMID- 24899937
TI  - 3'-Deoxy-3'-[(18)F]fluorothymidine and O-(2-[(18)F]fluoroethyl)-L-tyrosine PET in
      Patients with Suspicious Recurrence of Glioma after Multimodal Treatment: Initial
      Results of a Retrospective Comparative Study.
AB  - PURPOSE: The purpose of this study was to compare the uptakes and diagnostic
      accuracies between 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) and O-(2
      [(18)F]fluoroethyl)-L-tyrosine (FET) PET in patients with a clinical suspicion of
      having a recurrence of glioma after multimodality treatment. METHODS: Thirty-two
      patients who underwent FLT and FET PET due to abnormal enhancement on magnetic
      resonance (MR) images were included. According to surgical confirmation or follow
      up results, patients were divided into those with therapy-related benign changes
      (TRBCs) and those with recurrence. Recurrences were divided again into initial
      low-grade glioma (LGG) and high-grade glioma (HGG). The uptakes of FLT and FET
      were compared with the maximum standardized uptake value (SUVmax) and lesion-to
      normal ratio (LNR). The diagnostic accuracies were compared via a receiver
      operating-characteristic (ROC) curve analysis. RESULTS: The LNRs of FLT in
      recurrences with initial HGG (8.26 +/- 5.02) were significantly higher than those
      in recurrences with initial LGG (3.43 +/- 2.14) and TRBC (1.81 +/- 0.60). The
      LNRs of FET in recurrence with initial HGG (2.70 +/- 0.48) and LGG (3.03 +/-
      1.32) were significantly higher than those in the TRBC (1.60 +/- 0.47). The areas
      under the ROC curve (AUCs) of FLT and FET for initial LGG were 0.768 and 0.893,
      respectively. The AUCs of FLT and FET for initial HGG were 1.000 and 0.964.
      However, there were no statistical significances. The results for comparing with
      SUVmax were the same as those with LNR. CONCLUSIONS: Uptakes of FLT were
      different according to initial grade in patients with recurrent glioma, but those
      of FET were not. However, there were no statistical significances in the
      diagnostic accuracies according to initial grade between the two tracers in this
      study.

PMID- 24899938
TI  - Clinical Usefulness of (18)F-fluoride Bone PET.
AB  - PURPOSE: (18)F-fluoride bone positron emission tomography (PET) has been reported
      as a useful bone imaging modality. However, no clinical bone PET study had been
      performed previously in Korea. The authors investigated the usefulness of (18)F
      fluoride bone PET in Korean patients with malignant or benign bone disease.
      METHODS: Eighteen consecutive patients (eight women, ten men; mean age, 55 +/- 12
      years) who had undergone (18)F-fluoride bone PET for the evaluation of bone
      metastasis (n = 13) or benign bone lesions (n = 5) were included. The
      interpretation of bone lesions on (18)F-fluoride bone PET was determined by
      consensus of two nuclear medicine physicians, and final results were confirmed
      using combination of all imaging studies and/or clinical follow-up. The analysis
      was performed on the basis of lesion group. RESULTS: Thirteen patients with
      malignant disease had 15 lesion groups, among which seven were confirmed as
      metastatic bone lesions and eight were confirmed as non-metastatic lesions. (18)F
      fluoride bone PET correctly identified six of seven metastatic lesions
      (sensitivity, 86%), and seven of eight non-metastatic lesions (specificity, 88%).
      On the other hand, five patients with benign conditions had five bone lesion
      groups; four were confirmed as benign bone diseases and the other one was
      confirmed as not a bone lesion. (18)F-fluoride bone PET showed correct results in
      all the five lesion groups. CONCLUSIONS: (18)F-fluoride bone PET showed promising
      potential for bone imaging in Korean patients with malignant diseases as well as
      with various benign bone conditions. Therefore, further studies are required on
      the diagnostic performance and cost-effectiveness of (18)F-fluoride bone PET.

PMID- 24899939
TI  - Tc-99m diphosphonate as a potential radiotracer to detect sentinel lymph nodes in
      patients with breast cancer.
AB  - PURPOSE: To evaluate the potential of Tc-99m diphosphonate as a tracer for
      sentinel lymph node biopsy in breast cancer. METHODS: Lymphoscintigraphs of 35
      patients (50.9 +/- 10.2 years) with breast cancer were acquired after
      administering a subareolar intradermal injection of Tc-99m diphosphonate 18 h
      before surgery. Static images were taken within 15 min (early phase) and 15 h
      after injection (delayed phase). The lymphoscintigraphic identification rate was
      defined as the percentage of subjects studied with visible foci at axillae.
      Sentinel lymph node biopsies were performed using a gamma probe and by blue dye
      injection. Any node that was radioactive or stained with blue dye was labeled as
      a sentinel lymph node. Lymph nodes without radioactivity or blue dye staining
      were defined as non-sentinel lymph nodes. The intraoperative identification rate
      was defined as the percentage of patients with a radioactive sentinel lymph node.
      Percentages of lymphoid cells expressing S-100, CD83, and CD1a were compared.
      RESULTS: The lymphoscintigraphic identification rate was 94.3% (33/35) during the
      early phase and 96.9% (31/32) during the delayed phase, whereas the
      intraoperative identification rate was 94.3% (33/35). The mean percentages of
      lymphoid cells that stained positively for S-100 or CD83 were lower in sentinel
      lymph nodes than in non-sentinel lymph nodes (1.5% vs. 9.0% for S-100, and 4.5%
      vs. 9.3% for CD83, respectively, p = 0.0286). The mean percentages of lymphoid
      cells in sentinel lymph nodes and non- sentinel lymph nodes expressing CD1a were
      3.3% and 7.0%, respectively (p = ns). CONCLUSIONS: Tc-99m diphosphonate can
      reliably detect regional lymph nodes in breast cancer.

PMID- 24899940
TI  - Factors affecting changes in the glomerular filtration rate after unilateral
      nephrectomy in living kidney donors and patients with renal disease.
AB  - PURPOSE: We evaluated the factors affecting changes in the postoperative
      glomerular filtration rate (GFR) after unilateral nephrectomy in living kidney
      donors and patients with renal disease. METHODS: We studied 141 subjects who
      underwent living donor nephrectomy for renal transplantation (n = 75) or
      unilateral nephrectomy for renal diseases (n = 66). The GFR of the individual
      kidney was determined by Tc-99m DTPA scintigraphy before and after nephrectomy.
      By performing multiple linear regression analysis, we evaluated the factors that
      are thought to affect changes in GFR, such as age, sex, body mass index (BMI),
      preoperative GFR, preoperative creatinine level, operated side, presence of
      diabetes mellitus (DM), presence of hypertension (HTN), and duration of follow
      up. RESULTS: In both the donor nephrectomy and the disease nephrectomy groups,
      GFR increased significantly after nephrectomy (46.9 +/- 8.4 to 58.1 +/- 12.5 vs.
      43.0 +/- 9.6 to 48.6 +/- 12.8 ml/min, p < 0.05). In the donor nephrectomy group,
      age was significantly associated with change in GFR (beta = -0.3, p < 0.005). In
      the disease nephrectomy group, HTN, preoperative creatinine level, and age were
      significantly associated with change in GFR (beta = -6.2, p < 0.005; beta = 
      10.9, p < 0.01; beta = -0.2, p < 0.01, respectively). This compensatory change in
      GFR was not significantly related to sex, duration of follow-up, or operated side
      in either group. CONCLUSIONS: The compensatory change in the GFR of the remaining
      kidney declined with increasing age in both living kidney donors and patients
      with renal disease.

PMID- 24899941
TI  - Cerebral Toxoplasmosis in a Patient with AIDS on F-18 FDG PET/CT.
AB  - The distinction between primary central nervous system (CNS) lymphoma and
      nonmalignant lesions due to opportunistic infections, in particular cerebral
      toxoplasmosis, is important because of the different treatments involved. A 32
      year-old patient with AIDS was hospitalized for intermittent headaches. Brain
      magnetic resonance imaging (MRI) showed a small well-enhanced nodular lesion in
      the right frontal lobe. A fluorine-18 fluorodeoxyglucose (F-18 FDG) positron
      emission tomography (PET)/computed tomography (CT) scan showed moderate FDG
      uptake in the nodular lesion of the right frontal lobe. We present a case of
      cerebral toxoplasmosis in a patient with acquired immunodeficiency syndrome
      (AIDS) and the usefulness of F-18 FDG PET/CT in the differential diagnosis of the
      cerebral toxoplasmosis will be discussed. 

PMID- 24899942
TI  - Non-Specific Disease Mimicking Malignancy: Two Cases of FDG Uptake in the
      Extremities.
AB  - FDG PET is an imaging technique used to assess regional differences in glucose
      metabolism. A variety of diseases, including malignancy, can show abnormal FDG
      uptake in bone marrow. PET/CT demonstrated non-specific uptake in the extremities
      of two patients with fever of unknown origin (FUO). Both patients showed focal
      and symmetric FDG uptake in the bone marrow of the arms and legs. Although the
      results of these cases were not diagnostic, the unique uptake pattern of PET/CT
      should be considered a non-specific reactive change as well as malignancy or
      other possibilities in the initial differential diagnosis. 

PMID- 24899944
TI  - Radiography, Bone Scan, and F-18 FDG PET/CT Imaging Findings in a Patient with
      Paget's Disease.
AB  - BACKGROUND: A 52-year-old female patient sought evaluation at our hospital for an
      incidental abnormal finding on an abdominal radiograph. METHODS: The initial
      radiograph showed irregular sclerotic changes involving the right pelvic bone. At
      the same time, bone scintigraphy showed intense hot uptake in the right iliac and
      pubic bones. CT images showed characteristic thickening of the pelvic brim,
      suggesting the mixed phase of Paget's disease. RESULTS: The level of alkaline
      phosphatase (ALP) was 266 IU/l. (18)F-FDG PET/CT images also showed diffusely
      increased (18)F-FDG uptake in the right pelvic bone. However, the findings of
      (18)F-FDG PET/CT were less notable than those of bone scintigraphy. CONCLUSION:
      We report the imaging findings of a patient with Paget's disease evaluated by
      radiography, bone scintigraphy, and (18)F-FDG PET/CT.

PMID- 24899943
TI  - F-18 FDG PET Images of the Cervix at Various Time Points after the Loop
      Electrosurgical Excision Procedure.
AB  - F-18 FDG PET is useful for monitoring residual or recurrent tumors after surgical
      resection. We describe five F-18 FDG PET images of three patients who had
      cervical carcinoma and then underwent a loop electrosurgical excision procedure
      (LEEP). Two of the images were taken within 15 days and three at least 2 months
      after LEEP. The earlier F-18 FDG PET images revealed linear hypermetabolic
      lesions in the cervix that were produced by inflammation. This was confirmed by
      pathological analysis. The later F-18 FDG PET images did not reveal any
      remarkable hypermetabolism in the cervix without any treatment. These
      observations suggest that, to determine the response to LEEP therapy, F-18 FDG
      PET should not be performed within 15 days of the procedure. 

PMID- 24899945
TI  - Absent sternum as the first manifestation of bone metastasis on bone
      scintigraphy.
AB  - The sternum is known as a relatively common site for bone metastases by a variety
      of malignant neoplasms. The usual finding is increased radiotracer uptake on bone
      scintigraphy, and cold metastasis is distinctly unusual. In addition, total
      nonvisualization of the sternum presenting as bone metastasis is extremely rare.
      We describe two cases with similar findings (absent sternum showing no activity
      of the sternal segments on bone scintigraphy), which corresponded to metastatic
      involvement. These findings were shown to be the first manifestation of
      hepatocellular carcinoma in one patient and bone metastasis in another patient
      with ovarian cancer. 

PMID- 24899946
TI  - (18)F-FDG PET/CT with Contrast Enhancement for Evaluation of Axillary Lymph Node
      Involvement in T1 Breast Cancer.
AB  - BACKGROUND: (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography
      ((PET) safely predicts axillary status in patients with breast cancer, but is not
      sufficiently accurate in early breast cancer patients. This study analyzed the
      value of (18)F-FDG PET/computed tomography (CT) with contrast enhancement in
      detecting axillary lymph node involvement in T1 breast cancer patients. METHODS:
      Contrast-enhanced (18)F-FDG PET/CT was performed within 20 days of surgery in 143
      breast cancer patients with tumors <=2 cm in size. The patients underwent either
      axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB), and
      histopathology reports were used to provide the definitive diagnosis against
      which the contrast-enhanced (18)F-FDG PET/CT study results were compared.
      RESULTS: The sensitivity, specificity, and negative and positive predictive
      values of contrast-enhanced (18)F-FDG PET/CT in detecting axillary involvement
      were 70.0%, 92.2%, 88.8%, and 77.8%, respectively, in the entire series of 143
      patients, with eight false-positive and 12 false negative results. The false
      negative results were associated with the number of metastatic lymph nodes and
      the rate of FDG uptake. CONCLUSION: Contrast-enhanced (18)F-FDG PET/CT cannot
      replace histologic staging using SLNB in patients with breast cancer, but (18)F
      FDG PET/CT increases the sensitivity for predicting axillary node metastasis, and
      allows for a selective approach to either ALND or SLNB, even in patients with T1
      breast cancer.

PMID- 24899947
TI  - (18)F-FDG PET/CT is Useful for Pretreatment Assessment of the Histopathologic
      Type of Thymic Epithelial Tumors.
AB  - PURPOSE: This study was performed to assess the usefulness of (18)F
      fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) or PET/computed
      tomography (CT) for distinguishing thymic epithelial tumors according to World
      Health Organization (WHO) classifications. METHODS: We analyzed a total of 45
      patients (range, 29-75 years of age; mean, 55 years) with pathologically
      confirmed thymic epithelial tumors who underwent pretreatment (18)F-FDG PET or
      PET/CT between November 2003 and October 2009. The size, visual grading of uptake
      value, peak standardized uptake value (SUVpeak), uptake pattern, and contour of
      each tumor, and associated findings on PET or PET/CT, were analyzed relative to
      the three simplified WHO subgroups: less-invasive thymomas (types A and AB), more
      invasive thymomas (types B1, B2, and B3) and thymic carcinomas. We statistically
      assessed the relationship of (18)F-FDG PET or PET/CT findings with these
      simplified subgroups. RESULTS: Of the 45 patients, ten had less-invasive
      thymomas, 23 had more-invasive thymomas, and 12 had thymic carcinomas. The
      SUVpeak of the less- and more-invasive thymomas were significantly lower than
      those of thymic carcinomas (p < 0.000), but there was no difference in SUVpeak
      between less- and more-invasive thymomas. The visual grading scale (p < 0.000),
      uptake pattern (p = 0.001), and contour (p < 0.000) of the tumors differed
      significantly among the three simplified subgroups. CONCLUSION: The image
      findings of (18)F-FDG PET or PET/CT differed significantly by histologic
      subgroups. Pre-treatment evaluation with (18)F-FDG PET or PET/CT might be helpful
      in differentiating subgroups of thymic epithelial tumors.

PMID- 24899948
TI  - A New Synthesis of TE2A-a Potential Bifunctional Chelator for (64)Cu.
AB  - PURPOSE: The development of a new bifunctional chelator, which holds radiometals
      strongly in living systems, is a prerequisite for the successful application of
      disease-specific biomolecules to medical diagnosis and therapy. Recently, TE2A
      was reported to make kinetically more stable Cu(II) complexes than TETA. Herein,
      we report a new synthetic route to TE2A and explore its potential as a
      bifunctional chelator. METHODS: TE2A was synthesized using the regioselective
      alkylation of benzyl bromoacetate and successive deprotection of the methylene
      bridge and benzyl group. Salt-free TE2A was radiolabeled with (64)Cu and microPET
      imaging was performed to follow the clearance pattern of the (64)Cu-TE2A complex.
      TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was
      radiolabeled with (64)Cu. RESULTS: TE2A was prepared in salt-free form from
      cyclam in an overall yield of 74%. The microPET images showed that (64)Cu-TE2A is
      excreted rapidly from the body by the kidney and liver. TE2A was successfully
      conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A
      c(RGDyK) conjugate was radiolabeled with (64)Cu in 94% yield within 30 min.
      CONCLUSION: TE2A can be used by itself as a bifunctional chelator without any
      further structural modification.

PMID- 24899949
TI  - Prodrug-activating Gene Therapy with Rabbit Cytochrome P450 4B1/4-Ipomeanol or 2
      Aminoanthracene System in Glioma Cells.
AB  - OBJECTIVE: We determined the cytotoxic properties of cytochrome P450 4B1 (CYP4B1)
      activated 4-ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) in rat glioma to
      verify the CYP4B1/4-ipo or 2-AA system for prodrug-activating gene therapy.
      METHODS: The cyp4B1 cDNA was cloned into pcDNA3.1/Hygro from rabbit lung total
      RNA (pcDNA-cyp4B1). Lentiviral vector encoding firefly luciferase (fLuc) was
      infected into C6 (rat glioma), and the fLuc-expressing cell was selected (C6-L).
      After transfection with pcDNA-cyp4B1 vector into C6-L, the single clone
      expressing cyp4B1 gene was selected (C6-CL). Prodrug for various concentrations
      of 4-ipo or 2-AA was treated for 72 h and 96 h. The cell survival rate of C6-CL
      was determined using MTT assay and trypan-blue dye exclusion methods. RESULTS: By
      RT-PCR analysis, fLuc and CYP4B1 expression was detected in C6-CL, but not in C6.
      MTT assay and trypan-blue dye exclusion showed that IC50 of C6-CL was 0.3 mM and
      <0.01 mM after 4-ipo or 2-AA treatment at 96 h or 72 h exposure, respectively.
      Cell survivals of C6-CL were more rapidly reduced after treatment with 4-ipo or 2
      AA than those of C6-L cells. The cell survival rate with MTT and trypan-blue dye
      exclusion assay was well correlated with fLuc activity in C6-CL cells.
      CONCLUSION: CYP4B1-based prodrug-activating gene therapy may have the potential
      to treat glioma and the cytotoxic effects of CYP4B1 enzyme activated 4-ipo or 2
      AA in C6, and could be clearly determined by bioluminescent activity in C6-CL.

PMID- 24899950
TI  - CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes
      Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy.
AB  - PURPOSE: The authors evaluated whether the cytotoxicity of CD8+CTLs generated by
      combined hMUC1 vaccination and hNIS radioiodine gene therapy was enhanced in the
      presence of CpG in an established tumor model. METHODS: CMNF cells (CT26 cells
      expressing hMUC1, hNIS and Firefly luciferase) were transplanted into BALB/c
      mice. Four and 10 days later, tumor-bearing mice were immunized intramuscularly
      with pcDNA3.1 or pcDNA-hMUC1 or pcDNA-hMUC1+CpG, and subsequently administered
      PBS or (131)I [five groups (seven mice/group): referred to as the pcDNA3.1+PBS,
      phMUC1+PBS, pcDNA3.1+(131)I, phMUC1+(131)I, and phMUC1+(131)I+CpG groups]. The
      number of CD8+IFNr+ T cells of splenocytes as well as the number of CD8+IFNr+ T
      cells of splenocytes re-stimulated with CD11c+ cells was determined using FACS
      analysis. The activities of cytotoxic T cells (CTLs) from splenocytes were
      investigated. RESULTS: Marked tumor growth inhibition was observed in the
      phMUC1+(131)I and phMUC1+(131)I+CpG groups, but not in the other three single
      therapy groups. Particularly the number of CD8+IFN-gamma+ T cells of splenocytes
      was more increased in the phMUC1+(131)I+CpG group than in the phMUC1+(131)I
      group. The number of CD8+IFN-gamma+ T cells of splenocytes stimulated with CD11c+
      cells was the most enhanced in the phMUC1+(131)I+CpG group among the five groups.
      Concurrently, the activities of hMUC1-associated CTLs obtained from splenocytes
      in the phMUC1+(131)I+CpG group were significantly greater than in the other four
      groups (pcDNA+PBS, phMUC1+PBS, pcDNA+(131)I, phMUC1+(131)I, and
      phMUC1+(131)I+CpG, 16 +/- 2%, 20 +/- 1%, 30 +/- 2%, 60 +/- 2%, and 87 +/- 2%,
      respectively, P < 0.01). CONCLUSION: Our data suggest that adjuvant CpG ODNs can
      increase the killing activities of CTLs generated by combined hMUC1 DNA
      vaccination and hNIS radioiodine gene therapy.

PMID- 24899952
TI  - Small Cell Carcinoma of the Gallbladder: (18)F-FDG PET/CT Imaging Features-A Case
      Report.
AB  - The diagnostic role of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission
      tomography (PET)/computed tomography (CT) for gallbladder small cell carcinoma
      has not been reported. A knowledge of the imaging characteristic features of this
      malignancy can be useful. Here we report a rare case of a patient who had various
      diagnostic imaging modalities, including (18)F-FDG PET/CT. 

PMID- 24899951
TI  - The Prevalence and Characteristics of Brown Adipose Tissue in an (18)F-FDG PET
      Study of Koreans.
AB  - PURPOSE: The object of this study was to evaluate the prevalence and
      characteristics of brown adipose tissue (BAT) in Korean subjects using (18)F
      fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). METHODS: Six
      thousand and five consecutive (18)F-FDG PET/CT scans of 5,115 patients (3,007
      females and 2,108 males, mean age 53.5 years) were retrospectively reviewed. We
      characterized the nature of BAT, such as its location, and we assessed the
      influence of sex, age, body mass index (BMI), and temperature on BAT. RESULTS:
      The prevalence of BAT in Koreans in a single (18)F-FDG PET/CT scan in average
      conditions was 1.07%. The BAT detection rate was higher in females than males
      (1.32% vs 0.73%), and also with younger age (7.94% vs 0.73%), lower BMI (BMI with
      BAT, 21.1 vs BMI without BAT, 23.15) and cold outdoor temperature (1.65% vs
      0.49%). The most frequent location of BAT was the supraclavicular area (left,
      0.91%; right, 0.88%) and ventral neck area (left, 0.62%; right, 0.63%).
      CONCLUSIONS: The characteristics of BAT in Koreans are not different from those
      described for Caucasians. However, the low prevalence of BAT in our study might
      be related to some scan condition like ambient temperature, but further study is
      needed.

PMID- 24899953
TI  - Huge Varicose Inferior Mesenteric Vein: an Unanticipated (99m) Tc-labeled Red
      Blood Cell Scintigraphy Finding.
AB  - Ectopic varices (EcV) are enlarged portosystemic venous collaterals, which
      usually develop secondary to portal hypertension (PHT). Mesocaval collateral
      vessels are unusual pathways to decompress the portal system. Here we report the
      case of a huge varicose inferior mesenteric vein (IMV) that drained into
      perirectal collateral veins, demonstrated by (99m)Tc-labeled red blood cell (RBC)
      scintigraphy performed for lower gastrointestinal (GI) bleeding in a 14-year-old
      girl. This case illustrates the crucial role of (99m)Tc-labeled RBC scintigraphy
      for the diagnosis of rare ectopic lower GI varices. 

PMID- 24899954
TI  - Abdominal Mesh Implant Showing FDG Uptake on PET/CT.
AB  - F-18 fluorodeoxyglucose (FDG) uptake by a mesh implant might be caused by a
      foreign body granulomatous reaction with inflammation and fibrosis, which can be
      demonstrated by positron emission tomography/computed tomography (PET/CT). A 71
      year-old man underwent F-18 FDG PET/CT for the follow-up evaluation after an
      operation for colonic adenocarcinoma. On PET/CT imaging, there was a rectangular
      shaped FDG uptake (maximal standardized uptake value, maxSUV: 3.4) in the
      anterior abdominal wall. On the review of the medical records, the patient had a
      history of herniorrhapy for the reinforcement of the abdominal wall 2 months
      previously, using a mesh implant consisting of polytetrafluoroethylene (Teflon).
      We report a case of FDG uptake associated with surgical procedures including mesh
      implant on F-18 FDG PET/CT. 

PMID- 24899955
TI  - Multifocal Colonic Lesions Detected by (18)F-FDG PET/CT: Correlation with
      Histopathology and Gross Specimen.
AB  - A 73-year-old man underwent (18)F-fluorodeoxyglucose positron emission
      tomography/computed tomography ((18)F-FDG PET/CT) for the staging of colon
      cancer. The (18)F-FDG PET/CT revealed three colonic lesions. The histopathologic
      examination of the postoperative gross specimen revealed a tubular adenoma, a
      tubulovillous adenoma and an adenocarinoma. The maximal standardized uptake value
      (SUVmax) of a tubulovillous adenoma was much higher than that of adenocarcinoma.
      This patient could be considered as a representative case highlighting that
      SUVmax is not a reliable indicator for discriminating colon cancer from colonic
      adenomas. 

PMID- 24899956
TI  - Hypermetabolism of skeletal muscles following sexual activity: a normal
      variation.
AB  - A 46-year-old man with early gastric cancer at the gastric antrum underwent an F
      18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-computer
      tomography (CT) scan for staging. No definite abnormal FDG uptake of the stomach
      was shown. Incidentally, variable FDG uptake at the bilateral serratus muscles,
      abdominal muscles and muscles of both thighs (Fig. 1) was observed. He had no
      significant past medical history except recently diagnosed stomach cancer. On
      personal interview, he described having had sexual activity the night before the
      F-18 FDG PET/CT scan, although he was aware of needing to avoid physical activity
      before a PET scan. The F-18 FDG PET/CT scan was done at 2:00 p.m. Therefore, the
      hypermetabolism of individual skeletal muscles following sexual activity lasted
      over 12 h. This case illustrates the hypermetabolism of skeletal muscles
      following sexual activity as a normal variation. 

PMID- 24899957
TI  - Retroperitoneal Pleomorphic Liposarcoma Mimicking Adrenal Cancer in F-18 FDG
      PET/CT.
AB  - Liposarcoma is the second most common type of soft tissue sarcoma, but
      pleomorphic liposarcoma is the least common subtype. We present the case of a 42
      year-old man who had experienced intermittent left flank pain for a month. A
      large soft-tissue mass was detected by ultrasonography in a local clinic, and he
      was referred for further evaluation. Positron emission tomography/computed
      tomography (PET/CT) with F-18 fluoro-2-deoxy-D-glucose (F-18 FDG) showed intense
      uptake in the retroperitoneal mass, which mimicked an adrenal cancer. The patient
      underwent left radical nephroadrenalectomy, and the tumor was revealed to be a
      pleomorphic liposarcoma upon pathological examination. When there is a large
      retroperitoneal mass with intense F-18 FDG activity, the possibility of a
      pleomorphic liposarcoma should be considered. 

PMID- 24899959
TI  - Estimation of the Release Time from Isolation for Patients with Differentiated
      Thyroid Cancer Treated with High-dose I-131.
AB  - PURPOSE: Patients receiving high-dose I-131 to treat differentiated thyroid
      cancer are isolated from visitors to limit radiation exposure to reasonable
      levels. The appropriate isolation time is unclear and has not been reported in
      Korea. The purpose of this study was to estimate the isolation time and
      investigate the possibility of earlier release from isolation. METHODS: This
      study was a retrospective analysis of data from 71 patients (10 men and 61 women;
      mean age, 49 +/- 11.1 y) who received 3.7 GBq (47 patients), 5.55 GBq (23
      patients), or 7.4 GBq (1 patient) of I-131 between January 2008 and December
      2008. The radiation dose was measured with a fixed probe placed inside the
      isolation room. The total estimated dose equivalent (TEDE) to family members, the
      time required for the external dose rate to become <0.07 mSv/h, and the time
      required for whole-body retention to become <1.2 GBq were calculated. RESULTS: By
      the TEDE criterion (<5 mSv), 70 of 71 patients (98.6%) could have been released
      without isolation. By the external dose rate criterion, 10 of 71 (14.1%) and 60
      of 71 patients (84.5%) could have been released without isolation and within 24
      h, respectively. With whole-body retention criterion, 19 of 71 (26.8%) and 48 of
      71 patients (67.6%) could have been released within 24 h and within 48 h,
      respectively. CONCLUSIONS: Appropriate release times were estimated and compared
      using different criteria. Most patients could have been released without
      isolation or within 24 h of radiation treatment.

PMID- 24899958
TI  - (68)Ga-labeled radiopharmaceuticals for positron emission tomography.
AB  - (68)Ga is a promising emerging radionuclide for positron emission tomography
      (PET). It is produced using a (68)Ge/(68)Ga-generator, and thus, would enable the
      cyclotron-independent distribution of PET. However, new (68)Ga-labeled
      radiopharmaceuticals that can replace (18)F-labeled agents like
      [(18)F]fluorodeoxyglucose (FDG) are needed. Most of the (68)Ga-labeled
      derivatives currently used are peptide agents, but the developments of other
      agents, such as amino acid derivatives, nitroimidazole derivatives, and
      glycosylated human serum albumin, are being actively pursued in many
      laboratories. Thus, appearance of new (68)Ga-labeled radiopharmaceuticals with
      high impact are expected in the near future. Here, we present an overview of
      (68)Ga-labeled agents in terms of their clinical significances and relevances to
      the management of certain tumors, and pertinent pre-clinical developments. 

PMID- 24899960
TI  - Reproducibility of gallbladder ejection fraction measured by Fatty meal
      cholescintigraphy.
AB  - PURPOSE: There are conflicting data in the literature regarding the
      reproducibility of the gallbladder ejection fraction (GBEF) measured by fatty
      meal cholescintigraphy (CS). We aimed to test the reproducibility of GBEF
      measured by fatty meal CS. METHODS: Thirty-five subjects (25 healthy volunteers
      and 10 patients with chronic abdominal pain) underwent fatty meal CS twice in
      order to measure GBEF1 and GBEF2. The healthy volunteers underwent a repeat scan
      within 1-13 months from the first scan. The patients underwent a repeat scan
      within 1-4 years from the first scan and were not found to have chronic
      acalculous cholecystitis (CAC). Our standard fatty meal was composed of a 60-g
      Snickers chocolate bar and 200 ml full-fat yogurt. RESULTS: The mean +/- SD
      values for GBEF1 and GBEF2 were 52 +/- 17% and 52 +/- 16%, respectively. There
      was a direct linear correlation between the values of GBEF1 and GBEF2 for the
      subjects, with a correlation coefficient of 0.509 (p = 0.002). Subgroup data
      analysis of the volunteer group showed that there was significant linear
      correlation between volunteer values of GBEF1 and GBEF2, with a correlation
      coefficient of 0.473 (p = 0.017). Subgroup data analysis of the non-CAC patient
      group showed no significant correlation between patient values of GBEF1 and
      GBEF2, likely due to limited sample size. CONCLUSIONS: This study showed that
      fatty meal CS is a reliable test in gallbladder motility evaluation and that GBEF
      measured by fatty meal CS is reproducible.

PMID- 24899961
TI  - Radiation safety issues in y-90 microsphere selective hepatic radioembolization
      therapy: possible radiation exposure from the patients.
AB  - PURPOSE: The purpose of this study was to estimate the possible external
      radiation dose to other individuals from patients treated with Y-90 resin
      microspheres for unresectable hepatocellular carcinoma. METHODS: We designed the
      study prospectively to estimate the possible radiation dose to other individuals
      from patients who had been treated with Y-90 microspheres for unresectable
      hepatocellular carcinoma. We estimated the total effective dose equivalent (TEDE)
      using two methods: 'theoretical' TEDEs according to the administered activity and
      'measured' TEDE based on the 'measured' ambient radiation exposure rate. We
      compared the results from each method to determine when we can release patients
      from confinement at the earliest time complying with the patient release
      criteria. RESULTS: A total of 20 administrations of Y-90 resin microspheres were
      done in 18 patients. The average administered activity was 1.2 +/- 0.77 (0.28
      2.97) GBq. The 'theoretical' TEDEs were in the range of 0.8-10 MUSv. The
      'measured' TEDEs were in the range of 2.31-185 MUSv. The measured TEDEs tend to
      be higher than the theoretical TEDEs. The values of theoretical and measured TEDE
      were both far less than 1 mSv, the upper limit at which the licensee can release
      a patient without any written documents. CONCLUSION: The effective dose
      equivalent caused by the Y-90 microsphere administered patient is very low. It is
      safe in terms of radiation safety to the other individuals when Y-90 microsphere
      radioembolization therapy is done with dose less than 3 GBq. Because the measured
      TEDE tends to be higher than the theoretical TEDE, it is recommended to use
      'measured' TEDE for determining patient release.

PMID- 24899962
TI  - Imaging Atherosclerosis in the Carotid Arteries with F-18-Fluoro-2-deoxy-D
      glucose Positron Emission Tomography: Effect of Imaging Time after Injection on
      Quantitative Measurement.
AB  - PURPOSE: To compare F-18-fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission
      tomography/computed tomography (PET/CT) imaging at two different circulation
      times after injection of F-18 FDG in order to measure atherosclerosis in carotid
      arteries. METHODS: We assessed 12 patients with recent symptomatic plaques in the
      carotid arteries. F-18 FDG PET/CT carotid plaque imaging was performed for 20 min
      at 2 h after F-18 FDG injection in five patients and at 3 h in seven patients. We
      measured vessel wall uptake using the maximal standardized uptake value (SUV),
      and the mean and maximal blood target-to-background ratios (TBR) of the
      symptomatic carotid arteries. Blood pool activity (BPA) was measured as the mean
      SUV of the superior vena cava (SVC) and jugular vein of these 12 patients, and in
      14 age- and gender-matched patients who underwent whole-body F-18 FDG PET/CT
      examinations 1 h after injection. RESULTS: F-18 FDG PET/CT revealed visible F-18
      FDG uptake in all patients with symptomatic carotid plaques. Maximal SUV did not
      differ between groups evaluated at 2 h and 3 h (2.62 +/- 0.45 vs 3.00 +/- 0.85, p
      = 0.335). However, mean (2.04 +/- 0.22 vs 3.54 +/- 0.62, p < 0.05) and maximal
      (1.65 +/- 0.15 vs 2.70 +/- 0.42, p < 0.05) TBR values that were normalized to BPA
      in the SVC differ significantly. CONCLUSIONS: Symptomatic carotid plaques are
      visualized for a relatively short period of imaging time on >=1-h PET/CT images.
      Quantitative parameters of atherosclerotic carotid arteries are preserved or even
      increased over time, whereas those of blood pools are decreased.

PMID- 24899963
TI  - Behavior and awareness of thyroid cancer patients in Korea having non
      hospitalized low-dose radioiodine treatment with regard to radiation safety.
AB  - PURPOSE: With the recent increase in incidence of thyroid cancer, non
      hospitalized low-dose (NH-LD) radioiodine treatment (RIT) has also increased
      rapidly. The radioactivity limit that is allowed to be administered without
      hospitalization depends on individual calculation, based partly on patients'
      behavior. In this study, Korean patients' behavior in relation to radiation
      safety in NHLD RIT was surveyed. METHODS: A total of 218 patients who underwent
      NH-LD RIT of 1.1 GBq (131)I in a single center were surveyed. The patients
      underwent RIT with a standard protocol and the survey was performed by interview
      when they visited subsequently for a whole-body scan. The survey questionnaire
      included three parts of questions: general information, behavior relating to
      isolation during RIT, and awareness of radiation safety. RESULTS: After
      administration of radioiodine, 40% of patients who returned home used mass
      transportation, and another 47% went home by taxi or in car driven by another
      person. Isolation at home was generally sufficient. However, 7% of patients did
      not stay in a separate room. Among the 218 patients, 34% did not go home and
      chose self-isolation away from home, mostly due to concerns about radiation
      safety of family members. However, the places were mostly public places,
      including hotels, resorts, and hospitals. About half of the patients replied that
      access to radiation safety information was not easy and their awareness of
      radiation safety was not satisfactory. As a result, 45% of patients wanted
      hospitalized RIT. CONCLUSIONS: In many countries, including Korea, RIT is
      continuously increasing. Considering the radiation safety of patients' family
      members or the public and the convenience of patients, the pretreatment education
      of patients should be enhanced. In addition, the hospitalization of patients
      having low-dose therapy is recommended to be seriously considered and expanded,
      with the expansion of dedicated treatment facilities.

PMID- 24899964
TI  - Improved detection of lung or bone metastases with an I-131 whole body scan on
      the 7th day after high-dose I-131 therapy in patients with thyroid cancer.
AB  - PURPOSE: The purpose of this study is to compare post-therapy third day and
      seventh day I-131 whole body scans (3DWBS and 7DWBS) in detecting lung or bone
      metastasis from well-differentiated thyroid cancer. MATERIALS AND METHODS: We
      enrolled 52 patients with lung or bone metastasis out of 1,152 patients who were
      treated with high-dose I-131 therapy from January 2008 to June 2009. All patients
      underwent 3DWBS and 7DWBS. I-131 avidity was classified into three grades: no
      uptake, suspicious for uptake, and definite uptake. We compared the presence and
      grades of metastatic lesions on each scan. We categorized all cases into three
      groups based on I-131 uptake on each scan and compared several clinical
      parameters including FDG uptake and thyroglobulin (Tg) level among the groups.
      RESULTS: Sixty metastatic cases from 52 patients (45 lung and 15 bone metastases)
      were included. In 35 cases, I-131-avid metastatic lesions were detected by both
      3DWBS and 7DWBS (group A). In 15 cases, metastatic lesions were missed on 3DWBS
      but detected on 7DWBS (group B). In 10 cases, I-131 uptake was not detected on
      either 3DWBS or 7DWBS (group C). Ten of 45 cases (22.2%) of lung metastasis that
      were negative on 3DWBS were detected on 7DWBS (p = 0.002). Five of 15 cases
      (33.3%) of bone metastasis that were negative on 3DWBS were detected on 7DWBS (p
      = 0.0625). The serum Tg level (TSH stimulated) was significantly different among
      groups A, B, and C (p = 0.0030). However, after exclusion of cases without a
      history of I-131 therapy, there was no significant difference in serum Tg level
      among the groups (p = 0.2330). The number of cases with a prior history of
      metastasis was higher in group A than in group B (p = 0.0069). However, there was
      no significant difference in prior history of metastasis between groups A and C
      (p = 0.8107). CONCLUSION: 7DWBS showed more lung or bone metastatic lesions than
      3DWBS. After high-dose I-131 therapy, 7DWBS should be considered regardless of
      the results of the 3DWBS for the diagnosis of lung or bone metastasis from well
      differentiated thyroid cancer.

PMID- 24899965
TI  - Normal Physiologic and Benign Foci with F-18 FDG Avidity on PET/CT in Patients
      with Breast Cancer.
AB  - PURPOSE: The aim of this study was to evaluate the physiologic and benign F-18
      fluorodeoxyglucose (FDG) avid foci in patients with breast cancer. METHODS: On
      309 F-18 FDG PET/CT scans of 241 women with breast cancer, the hypermetabolic
      lesions compared with the surrounding normal region were evaluated
      retrospectively. Available reports of other relevant radiological imaging,
      medical records, and follow-up PET/CT were reviewed for explanations of the
      abnormal uptake. RESULTS: Among the 70 physiologic foci, muscular uptake of the
      lower neck following the surgical and/or radiation therapy of ipsilateral breast
      (29%), hypermetabolic ovaries (16%) and uterine (10%) uptake during the ovulatory
      and menstrual phases during the normal menstrual cycle were identified, and also
      hypermetabolic brown fat in cold-induced thermogenesis (7%), non-specific bowel
      uptake (35%) were observed. Among the 147 benign lesions, sequelae of the chest
      wall and breasts following surgical and/or radiation therapy, were often observed
      (27%). Hypermetabolic thyroid glands were noted as adenomas and chronic
      thyroiditis (18%). Reactive hyperplasia of cervical or mediastinal lymph nodes
      (32%), degenerative osteoarthritis and healed fractures (15%), hypermetabolic
      benign lung lesions (6%) were observed. CONCLUSION: Altered physiologic and
      benign F-18 FDG uptake in the lower cervical muscle and chest wall following
      ipsilateral breast surgery or radiotherapy were common, and also normal
      physiologic uptake in ovary and uterus, brown fat, thyroid were considered as
      predominant findings in women patients with breast cancer. Knowledge of these
      findings might aid in the interpretation of FDG PET/CT in patients with breast
      cancer.

PMID- 24899966
TI  - Ovarian mass mimicking malignancy: a case report.
AB  - A 32-year-old female who suffered from abdominal pain underwent (18)F
      fluorodexoyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) for the diagnostic workup of pelvic mass lesions. Cystic mass lesions in
      the bilateral ovaries showed wall thickening and intense hypermetabolism along
      the rim. In addition, multifocal intense hypermetabolic lymphadenopathies were
      seen in the left paraaortic lymph node (LN), aortocaval LN, and both common iliac
      LNs. We interpreted these findings as bilateral ovarian cancer with
      retroperitoneal metastatic lymphadenopathies rather than endometriosis with
      reactive lymphadenopathies. However, histopathological examination confirmed the
      ovarian mass lesions as tubo-ovarian abscesses. We report a case that even if
      simultaneous hypermetabolic retroperitoneal LNs are seen, intense hypermetabolic
      lesions in both ovaries can be in consequence of inflammatory change. 

PMID- 24899967
TI  - Endotracheal Metastasis Seen on FDG PET/CT in a Patient with Previous Colorectal
      Cancer.
AB  - Endotracheal/endobronchial metastasis, which is from either primary bronchogenic
      carcinoma or a tumor of non-pulmonary origin, is a rare but life-threatening
      condition. Among the different locations in the tracheobronchial tree, the
      trachea is an extremely rare location for metastasis from extrapulmonary tumor.
      To the best of our knowledge, endotracheal metastasis that was clearly visualized
      by F-18 FDG PET/CT has not been previously reported. We herein report on a
      patient with a FDG-avid endotracheal eccentric mass that was confirmed as
      metastasis from rectal cancer. 

PMID- 24899968
TI  - Multiple Skeletal Muscle Metastases in a Case of Transitional Cell Carcinoma of
      Bladder Detected by F-18 FDG PET/CT.
AB  - We present a case of poorly differentiated muscle invasive transitional cell
      carcinoma in a 64-year-old male diagnosed with FDG-avid mass in the urinary
      bladder wall and multiple skeletal muscles visualised on F-18 FDG PET/CT. 

PMID- 24899969
TI  - Hypermetabolic Axillary Mass on (18)F FDG PET/CT: Breast Cancer Arising from
      Accessory Breast Tissue.
AB  - Differential diagnosis among several causes of axillary malignant mass is
      important. The most common cause of palpable malignant axillary mass is
      metastatic lymphadenopathy. Although carcinoma arising from ectopic breast tissue
      is rare, the diagnosis should be kept in mind when evaluating malignant axillary
      mass. In this report we present a case with carcinoma arising from ectopic breast
      tissue. (18)F FDG PET/CT was performed for the purpose of localizing primary
      breast cancer lesion and systemic evaluation. PET/CT showed hypermetabolic
      lesions only in the right axilla. There is no evidence of malignancy in both
      breasts. When nuclear physicians encounter a hypermetabolic axillary mass
      indicating malignant lesion without evidence of primary breast malignant lesion,
      carcinoma arising from ectopic breast tissue should be included in the
      differential diagnosis. 

PMID- 24899970
TI  - Unexpectedly Diagnosed Caroli's Disease on HIDA Scintigraphy in a Patient with
      Calculous Cholecystitis.
AB  - Caroli's disease, which is a rare condition with congenital dilatation of the
      intrahepatic bile ducts, is usually diagnosed postoperatively. The clinical
      suspicion in a patient with gallstones and choledocholithiasis presenting with
      dilated intrahepatic biliary radicles and jaundice is usually an obstructive
      etiology. However, scintigraphic evaluation of this entity, as in this case,
      gives additional information on liver function, biliary drainage and predisposing
      conditions like Caroli's disease, which could be missed otherwise. 

PMID- 24899971
TI  - False-Positive Axillary Lymph Node on F-18 FDG PET/CT due to Moxibustion Therapy.

PMID- 24899973
TI  - Quantitative measurement of serum hepatitis B surface antigen using an
      immunoradiometric assay in chronic hepatitis B.
AB  - PURPOSE: Measurement of serum hepatitis B virus surface antigen (HBsAg) levels is
      important for the management of chronic hepatitis B patients in terms of
      monitoring response to antiviral therapy. This study aimed to evaluate the
      diagnostic performance of a new diagnostic kit, which quantitatively measures
      serum HBsAg level using an immunoradiometric assay (IRMA)-based method.
      Measurements were compared with those obtained using a chemiluminescent
      microparticle immunoassay (CMIA)-based method. METHODS: The blood samples of 96
      patients with chronic hepatitis B were used in this study. Copy numbers of serum
      hepatitis B virus (HBV) DNA were determined in 23 of these samples. The
      correlation between and the concordance of IRMA and CMIA results were determined
      using Pearson's correlation coefficients. P values of 0.05 were considered to be
      statistically significant throughout. RESULTS: Laboratory diagnoses based on IRMA
      were wholly in agreement with those based on CMIA. Furthermore, serum HBsAg
      levels by IRMA were found to be highly correlated with those determined by CMIA
      (correlation coefficient R (2) = 0.838, p < 0.001). Serum HBsAg level and serum
      HBV DNA copies were found to be linearly related by both methods (R (2) = 0.067,
      p = 0.316 by IRMA, and R (2) = 0.101, p = 0.215 by CMIA). CONCLUSION: The
      diagnostic performance of the investigated IRMA method of determining HBsAg
      levels was found to be comparable with that of a CMIA-based method in chronic
      hepatitis B patients.

PMID- 24899974
TI  - Depiction of Nidi and Fibrovascular Zones of Osteoid Osteomas Using Gamma
      Correction Tc-99m HDP Pinhole Bone Scan and Conventional Radiograph, and
      Correlation with CT, MRI, and PVC Phantom Imaging.
AB  - PURPOSE: For the precise imaging diagnosis of osteoid osteoma (OO), the
      identification of the nidus and fibrovascular zone (FVZ) is essential. However,
      the latter sign has received little attention because it is difficult to
      demonstrate. We applied the recently introduced gamma correction (GC) to depict
      the FVZ on pinhole bone scan (PBS), conventional radiography (CR), and computed
      tomography (CT). Non-gamma correction MRI was also analyzed for reference.
      METHODS: Ten patients with histologically proven diagnoses of OO were enrolled in
      this retrospective study. PBS, CR, and CT were processed by GC to demonstrate the
      nidi and FVZ as distinct yet integrating components of OO. PBS was performed
      using a 4-mm pinhole collimator 3 h after iv injection of 925 to 1,110 MBq (25 to
      30 mCi) of Tc-99m HDP, and anteroposterior and mediolateral CR and transverse CT
      were taken according to the standard technique. MRI sequences included T1- and T2
      weighted images. For gamma correction, we utilized the Photo Correction Wizard
      program of ACD Photo Editor v3.1. A team of three qualified nuclear physician
      radiologists, two nuclear physicians, and one MRI specialist read bone scans,
      radiographs, and MRIs of OO according to each specialty, and orthopaedic aspects
      and histology were reviewed by one qualified orthopedic surgeon and two qualified
      pathologists, respectively. Each observer first read the images separately with
      basic information about the aim of the study given and then in concert.
      Interpretive disagreement was settled by discussion and consensus. RESULTS: On
      pinhole scan, nidi were presented as areas of intense tracer uptake in all cases,
      and, importantly after GC, a thin ring-like zone with lower tracer uptake became
      visible in seven out of ten cases. GCCR also revealed a thin lucent zone that
      circumscribed the nidi in six out of ten cases and GCCT in two of four cases.
      MRI, without GC, presented nidi with high signal in the center and a thin ring
      like zone with low signal in the periphery in five out of six cases. Ring-like
      zones were 1-2 mm in thickness and circumscribed the nidus as an integrated part
      and, hence, were morphologically interpreted as FVZ. Histologically, the presence
      of a variously mineralized FVZ was confirmed in four cases, but individual locus
      by-locus image-histology correlation could not be accompolished because specimens
      were fragmentary. In the FVZ, tracer uptake was lower than in nidi, presumably
      reflecting that bone metabolism in the two parts differs as in their histology.
      Statistically, no significant correlation existed between the duration of
      symptoms and imaging demonstrability of the FVZ (Spearman's test r = -0.057, p =
      0.877), but parallelism existed in the demonstrability of the FVZ among GC PBS,
      CR, and CT, and non-correction MRI. CONCLUSIONS: GC was useful to enhance the
      resolution of PBS, CR, and CT in OO so that both the nidi and FVZ were separately
      imaged. The use of CG PBS and CR in combination is recommended for the specific
      diagnosis of OO with information about bone metabolism and anatomical
      characteristics. PBS and CR are economical and widely available.

PMID- 24899975
TI  - Relation between fluorodeoxyglucose uptake and glucose transporter-1 expression
      in gastric signet ring cell carcinoma.
AB  - PURPOSE: Gastric signet ring cell carcinoma (GSRC) is known to have low
      fluorodeoxyglucose (FDG) uptake. The aim of the study was to investigate the
      relation between FDG uptake and glucose transporter (GLUT)-1 expression and
      clinicopathologic parameters in cases of GSRC. MATERIALS AND METHODS: Forty
      patients (28 men, mean age 54 +/- 12 years) with histologically confirmed GSRC
      who underwent pre-operative [(18)F]FDG PET/CT were enrolled. Maximum standardized
      uptake values (SUVmax) were compared with clinicopathologic parameters and GLUT-1
      expression. Cases were divided based on GLUT-1 expression in tumor tissues into a
      membranous group (n = 17) and a cytoplasmic group (n = 23). RESULTS: Mean SUVmax
      was significantly higher in the membranous group than in the cytoplasmic group
      (6.06 +/- 2.79 vs. 3.67 +/- 1.54, P = 0.03). Gastric wall invasion, depth of
      invasion, extent of LN metastasis, overall stage, and tumor size were found to be
      related to SUVmax. On the other hand, age, sex, and the presence of distant
      metastasis were not related to SUVmax. Multivariate analysis revealed that
      membranous GLUT-1 expression and the extent of LN metastasis independently
      predicted high FDG uptake. CONCLUSIONS: This study demonstrates that high FDG
      uptake is mediated by membranous GLUT-1 expression in GSRC.

PMID- 24899972
TI  - Current molecular imaging positron emitting radiotracers in oncology.
AB  - Molecular imaging is one of the fastest growing areas of medical imaging.
      Positron emission tomography (PET) has been widely used in the clinical
      management of patients with cancer. Nuclear imaging provides biological
      information at the cellular, subcellular, and molecular level in living subjects
      with non-invasive procedures. In particular, PET imaging takes advantage of
      traditional diagnostic imaging techniques and introduces positron-emitting probes
      to determine the expression of indicative molecular targets at different stages
      of cancer. (18)F-fluorodeoxyglucose ((18)F-FDG), the only FDA approved
      oncological PET tracer, has been widely utilized in cancer diagnosis, staging,
      restaging, and even monitoring response to therapy; however, (18)F-FDG is not a
      tumor-specific PET tracer. Over the last decade, many promising tumor-specific
      PET tracers have been developed and evaluated in preclinical and clinical
      studies. This review provides an overview of the current non-(18)F-FDG PET
      tracers in oncology that have been developed based on tumor characteristics such
      as increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis,
      and tumor-specific antigens and surface receptors. 

PMID- 24899976
TI  - The Prognostic Value of the Metabolic Tumor Volume in FIGO stage IA to IIB
      Cervical Cancer for Tumor Recurrence: Measured by F-18 FDG PET/CT.
AB  - PURPOSE: The purpose of this study was to evaluate the prognostic value of the
      metabolic tumor volume (MTV), in FIGO stage IA-IIB cervical cancer patients,
      measured by F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)
      imaging. METHODS: Forty-five patients with invasive cervical cancer who underwent
      FDG-PET imaging were recruited. Metabolically active tumor regions were
      delineated on the pretreatment FDG-PET scans by encompassing regions equal to or
      greater than an standardized uptake value (SUV) of 40% of the peak tumor
      intensity. The relationship of the metabolic tumor volume (MTV) to the disease
      free survival was analyzed. The MTV of the cervical cancer was compared with
      pathological and clinical prognostic factors, including lymph node metastasis,
      parametrial invasion, the depth of invasion, resection margins, tumor
      differentiation and FIGO stages. RESULTS: Cox proportional hazard regression
      analysis showed that the MTV was a significant independent predictor of
      recurrence of cervical cancer (p = 0.027). Patients with an MTV of >20 cm(3) had
      a significantly reduced disease-free survival compared with patients with an MTV
      <= 20 cm(3) (p = 0.029). The correlation of the MTV with traditional prognostic
      factors showed significantly higher values in patients that were lymph node (LN)
      metastasis positive (p = 0.028) and parametrial invasion positive (p = 0.022).
      The MTV significantly differed among the groups according to tumor
      differentiation (p = 0.0319) and FIGO stage (p = 0.001). CONCLUSION: The MTV
      measured by FDG-PET was an independent prognostic factor for tumor recurrence in
      patients with stage IA-IIB cervical cancer. These findings must be confirmed by
      large population based prospective studies.

PMID- 24899977
TI  - Prognostic Value of Metabolic Tumor Volume Measured by (18)F-FDG PET/CT in
      Locally Advanced Head and Neck Squamous Cell Carcinomas Treated by Surgery.
AB  - PURPOSE: We assessed the prognostic value of metabolic tumor volume (MTV)
      measured using(18)F-fluorodeoxyglucose (FDG) positron emission
      tomography/computed tomography (PET/CT) inpatients with locally advanced head and
      neck squamous cell carcinoma (HNSCC). METHODS: We retrospectively reviewed 56
      patients (51 men, five women; mean age 56.0 +/- 8.8years) who had locally
      advanced HNSCC and underwent FDG PET/CT for initial evaluation. All patients had
      surgical resection and radiotherapy with or without concurrent chemotherapy. The
      peak standardized uptake value (SUVpeak) and MTV of the target lesion, including
      primary HNSCC andmetastatic cervical lymph nodes, were measured from FDG PET/CT
      images. We compared SUVpeak, MTV, and clinicopathologic variables such as age,
      Eastern Cooperative Oncology Group (ECOG) performance status, pN stage, pT stage,
      TNM stage, histologic grade and treatment modality to disease-free survival (DFS)
      and overall survival (OS). RESULTS: On the initial FDG PET/CT scans, the median
      SUVpeak was 7.8 (range, 1.8-19.0) and MTV was17.0 cm(3) (range, 0.1-131.0 cm(3)).
      The estimated 2-year DFS and OS rates were 67.2% and 81.8%. The cutoff points of
      SUVpeak 6.2 and MTV 20.7 cm(3) were the best discriminative values for predicting
      clinical outcome. MTV and ECOG performance status were significantly related to
      DFS and OS on univariate and multivariate analyses (p < 0.05). CONCLUSION: The
      MTV obtained from initial FDG PET/CT scan is a significant prognostic factor for
      disease recurrence and mortality in locally advanced HNSCC treated with surgery
      and radiotherapy with or without chemotherapy.

PMID- 24899978
TI  - Evaluation of Adrenal Masses in Lung Cancer Patients Using F-18 FDG PET/CT.
AB  - PURPOSE: The aim of this study was to assess the diagnostic efficacy of PET/CT
      using various parameters for the characterization of adrenal nodules in lung
      cancer patients. METHODS: Sixty-one adrenal nodules in 51 lung cancer patients
      were evaluated. The final diagnosis was based on histology (n = 2) or imaging
      follow-up (n = 59, range of follow-up: 7-57 months, median 27 months). Each
      adrenal nodule was analyzed using four parameters of PET/CT: the maximum
      standardized uptake value (SUVmax), the adrenal nodule/liver ratio of the SUV
      (SUV ratio), Hounsfield units (HU) and size. The optimal cutoff of each parameter
      for the identification of metastatic nodule was determined by ROC analysis and
      then the diagnostic efficacy was compared among the parameters. RESULTS: Of the
      61 adrenal nodules, 45 (73%) were considered metastasis. The optimal cutoff
      values of the parameters were SUVmax >2.7, SUV ratio >1.3, HU >18 and size >20
      mm, respectively. The sensitivity, specificity and accuracy by SUVmax >2.7 were
      88.9%, 87.5% and 88.5%, and those by SUV ratio >1.3 were 84.4%, 100% and 88.5%,
      respectively. The combination of SUV ratio >1.3 and HU >18 had sensitivity of
      97.7%, specificity of 81.2% and accuracy of 93.4% to predict adrenal metastasis
      in patients with lung cancer. CONCLUSION: SUV ratio from F-18 FDG PET/CT could
      identify the adrenal metastasis in lung cancer patients. The combination of SUV
      ratio and HU can improve the accuracy of differentiating benign and metastatic
      adrenal lesions in lung cancer patients.

PMID- 24899980
TI  - Osteonecrosis Mimicking Bone Metastasis in Femoral Head on (18)F-FDG PET/CT: A
      Case Report.
AB  - A 77-year-old woman underwent chemotherapy, radiotherapy, and brachytherapy for
      cervical cancer 9 years ago. On a follow-up (18)F-fluorodeoxyglucose (FDG) PET/CT
      image, focal FDG uptake was noted in a focal osteolytic lesion in the right
      femoral head. During magnetic resonance imaging, this lesion showed subchondral
      dark-signal-intensity rim on T1-weighted image and double line sign on T2
      weighted image, suggestive of osteonecrosis. The lesion was pathologically
      confirmed as osteonecrosis after surgery. This case demonstrates that
      osteonecrosis of the femoral head may demonstrate focal FDG uptake mimicking bone
      metastasis. 

PMID- 24899979
TI  - Usefulness of Bremsstrahlung Images after Intra-arterial Y-90 Resin Microphere
      Radioembolization for Hepatic Tumors.
AB  - PURPOSE: Y-90 resin microsphere radioembolization is used to treat inoperable
      hepatic tumors. After injection of Y-90 resin microsphere, the only method to
      visualize the distribution of Y-90 is the scintigraphic imaging of bremsstrahlung
      radiation. The purpose of this study was to evaluate the characteristics and
      usefulness of bremsstrahlung imaging in Y-90 resin microsphere treatment.
      METHODS: Twenty patients (22 administrations) underwent intra-arterial Y-90 resin
      microsphere treatment. For pre-treatment planning, images of Tc-99m albumin
      macroaggregate (MAA) arterial injection and hepatic contrast angiography were
      obtained. Post-treatment bremsstrahlung images were taken and compared with pre
      treatment images. The extrahepatic activity was evaluated on bremsstrahlung
      images. To correlate the size and vascularity of the tumors with tumor
      visualization on bremsstrahlung images, the individual tumors were grouped
      according to visualization on each image and compared with one another by size
      and tumor-to-normal ratio. RESULTS: All post-therapeutic bremsstrahlung images
      showed similar contours of the liver with pre-treatment angiography. No
      extrahepatic activity was seen in all cases. The visualized tumors on
      bremsstrahlung images were significantly larger than the non-visualized tumors.
      Tumor-to-normal ratios of the visualized tumors on bremsstrahlung images were
      significantly higher than those of the non-visualized tumors. CONCLUSIONS:
      Bremsstrahlung images after intra-arterial Y-90 resin microsphere treatment are
      useful in evaluating the intrahepatic distribution of radioisotope and detecting
      possible extrahepatic activity.

PMID- 24899981
TI  - Renal Metastasis from Follicular Thyroid Carcinoma Diagnosed by I-131 Whole-body
      Scan Mimicking Renal Cell Carcinoma on Contrast-Enhanced Computed Tomography.
AB  - Clinically detectable well-differentiated metastatic thyroid carcinoma to the
      kidney is rare and should be differentiated from primary renal malignancy. We
      report a case of renal metastases from follicular thyroid carcinoma (FTC)
      diagnosed by I-131 whole body scan. Additional features of this case different
      from previous case reports are solitary renal metastasis on I-131 whole body scan
      and mimicry of renal cell carcinoma on contrast-enhanced computed tomography. 

PMID- 24899982
TI  - Neurolymphomatosis on F-18 FDG PET/CT and MRI Findings: A Case Report.
AB  - Neurolymphomatosis is a rare manifestation of malignant lymphoma. A 74-year-old
      man, in complete remission from diffuse large B cell lymphoma, presented with a
      loss of pain and temperature sensation in the left hemiface and left upper
      extremity, and motor weakness in the left upper and both lower extremities.
      Cerebrospinal fluid analysis and brain magnetic resonance imaging (MRI) findings
      were negative. Combined fluorine-18 fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG-PET/CT) revealed multiple linear
      hypermetabolic lesions along the mandibular branch of the left trigeminal nerve,
      left brachial plexus, right axillary nerve, right suprarenal plexus, right
      adrenal gland, right femoral nerve, and both sciatic nerves, which corresponded
      to the patient's complex neurologic symptoms. C-spine and pelvic MRI revealed
      diffuse thickening with enhancement in the left brachial plexus and in the
      proximal portion of the left sciatic nerve, but negative findings for other sites
      identified by FDG-PET/CT. These findings suggest that FDG-PET/CT can detect
      peripheral nerve infiltration by malignant lymphoma earlier than MRI. Thus, if a
      patient with a history of lymphoma presents with neurologic symptoms, FDG-PET/CT
      should be performed to evaluate neurolymphomatosis. 

PMID- 24899983
TI  - (18)F-FDG PET Demonstration of Cancer Recurrence Presenting as Dermatomyositis in
      a Rare Case of Primary Pleural Lymphoma.
AB  - Dermatomyositis (DM) or polymyositis (PM) are possibly considered to have an
      association with malignancies. We describe a case of dermatomyositis in which
      (18)F-fluorodeoxy glucose (FDG)positron emission tomography (PET) was able to
      detect cancer recurrence earlier than any other modality in a patient with a
      history of primary pleural lymphoma, a very rare condition of malignancy.
      Further, a typical finding of dermatomyositis is diffuse hypermetabolism in the
      bilateral proximal shoulder and pelvic girdle areas was shown on (18)F-FDG PET,
      which can implicate the inflammatory process in the skeletal muscle in
      dermatomyosistis. This case well illustrates the characteristic (18)F-FDG
      findings of dermatomyositis as well as a capability of (18)F-FDG PET in detection
      of recurrence of lymphoma, even in a rare condition. 

PMID- 24899984
TI  - Incidental Hiatal Hernia Detected with Meckel's Scintigraphy.

PMID- 24899985
TI  - What are the Best Ways to Reduce the False-positive Rate of 18F-FDG PET/CT in
      Patients with Breast Cancer?

PMID- 24899986
TI  - Development of (166)Ho-phytate Complex for Radiosynovectomy.
AB  - BACKGROUND: (66)Ho-chloride was obtained by bombardment of natural Ho(NO3)3
      dissolved in acidic media using thermal neutron flux (4-5 * 10(13) n.cm(-2).s(
      1)). METHODS: (166)Ho-holmium chloride (185 MBq) was used successfully for
      preparation of (166)Ho-phytate complex with high radiochemical purity (>99.9 %,
      ITLC, MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability
      and viscosity were checked in the final solution up to 2 days. The prepared
      complex solution (60 MUCi/100 MUl) was injected intraarticularly to male rat knee
      joints. Leakage of radioactivity from the injection site and its distribution in
      organs were investigated up to 2 days. RESULTS: Approximately all of the injected
      dose had remained in the injection site 2 days after injection. CONCLUSION: The
      complex was proved to be a feasible agent for cavital radiotherapy in oncology
      and rheumatology.

PMID- 24899988
TI  - Total Thyroidectomy in the Mouse: the Feasibility Study in the Non-thyroidal
      Tumor Model Expressing Human Sodium/Iodide Symporter Gene.
AB  - PURPOSE: This study sought to probe the feasibility of performing total
      thyroidectomy in the mouse using a non-thyroidal hNIS expressing tumor model.
      MATERIALS AND METHODS: Our thyroidectomy protocol included thorough excision of
      both lobes and the isthmus. For evaluating the completeness of thyroidectomy, we
      compared the (99m)Tc-pertechnetate scans taken before and after thyroidectomy.
      The prostate cancer cell line was subcutaneously inoculated 2 weeks after the
      thyroidectomy. When the tumor reached 5-10 mm in diameter, Ad5/35-E4PSESE1a-hNIS
      was injected intratumorally, and (131)I scans were performed. The radioiodine
      uptakes of the neck and the tumor were compared with those of the other regions.
      RESULTS: Total thyroidectomy was performed in 13 mice. Although 38.5% died during
      or just after thyroidectomy, the others survived in good health for 2 months.
      Thyroid tissue was completely eliminated using our protocol; the residual uptake
      of (99m)Tc-pertechnetate was minimal in the neck area. The neck/background uptake
      ratio after thyroidectomy was significantly lower than that before thyroidectomy
      (p < 0.05). Non-thyroidal tumor models were successfully established in all the
      surviving mice. Radioiodine accumulation in the tumors was visualized on (131)I
      scans, and the neck uptakes were minimal. CONCLUSION: Using our total
      thyroidectomy protocol, we successfully established a hNIS-transfected prostate
      cancer model with a minimal accumulation of radioiodine in the neck. The
      relatively high mortality after surgery can be a problem, and this might be
      reduced by minimizing the surgical stress.

PMID- 24899987
TI  - Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer
      Progression.
AB  - PURPOSE: L-type amino acid transporter 1 (LAT1) is essential for the transport of
      large neutral amino acids. However, its role in breast cancer growth remains
      largely unknown. The purpose of the study is to investigate whether LAT1 is a
      potential biomarker for the diagnosis and treatment of breast cancer. METHODS:
      LAT1 mRNA and protein levels in breast cancer cell lines and tissues were
      analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast
      cancer cell tumorigenesis were assessed with soft agar assay. The imaging of
      xenograft with anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti
      [(18)F]FACBC) PET was assessed for its diagnostic biomarker potential. RESULTS:
      Normal breast tissue or low malignant cell lines expressed low levels of LAT1
      mRNA and protein, while highly malignant cancer cell lines and high-grade breast
      cancer tissue expressed high levels of LAT1. In addition, higher expression
      levels of LAT1 in breast cancer tissues were consistent with advanced-stage
      breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-amino
      bicyclo[2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with
      siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A
      leucine analog, anti-[(18)F]FACBC, has been demonstrated to be an excellent PET
      tracer for the non-invasive imaging of malignant breast cancer using an
      orthotopic animal model. CONCLUSIONS: The overexpression of LAT1 is required for
      the progression of breast cancer. LAT1 represents a potential biomarker for
      therapy and diagnosis of breast cancer. Anti-[(18)F]FACBC that correlates with
      LAT1 function is a potential PET tracer for malignant breast tumor imaging.

PMID- 24899990
TI  - Prognostic Value of Primary Tumor Uptake on F-18 FDG PET/CT in Patients with
      Invasive Ductal Breast Cancer.
AB  - PURPOSE: To determine the prognostic implications of pretreatment F-18 FDG PET/CT
      in patients with invasive ductal breast cancer (IDC), we evaluated the
      relationship between FDG uptake of the primary tumor and known prognostic
      parameters of breast cancer. Prognostic significance of tumoral FDG uptake for
      the prediction of progression-free survival (PFS) was also assessed. MATERIALS
      AND METHODS: Fifty-five female patients with IDC who underwent pretreatment F-18
      FDG PET/CT were enrolled. The maximum standardized uptake value of the primary
      tumor (pSUVmax) was compared with clinicopathological parameters including tumor
      size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal
      growth factor receptor2 (HER2), axillary lymph node (LN) metastasis, and stage.
      The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier
      method. RESULTS: A high pSUVmax was significantly related to a higher stage of
      tumor size (P < 0.05), grade (P < 0.001), and stage (P < 0.001). pSUVmax was
      significantly higher in ER-negative tumors (P < 0.001), PR-negative tumors (P <
      0.001), and positive LN metastasis (P < 0.01), but not different according to
      HER2 status. pSUVmax was significantly higher in patients with progression
      compared to patients who were disease-free (10.6 +/- 5.1 vs. 4.7 +/- 3.5, P <
      0.001). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.6
      to be the optimal cutoff for predicting PFS (sensitivity; 86.7%, specificity;
      82.5%). The patients with a high pSUVmax (more than 6.6) had significantly
      shorter PFS compared to patients with a low pSUVmax (P < 0.0001). CONCLUSIONS:
      pSUVmax on pretreatment F-18 FDG PET/CT could be used as a good surrogate marker
      for the prediction of progression in patients with IDC.

PMID- 24899989
TI  - Usefulness of F-18 FDG PET/CT in Assessment of Recurrence of Cervical Cancer
      After Treatment.
AB  - OBJECTIVE: Until now, serum tumor markers, physical examination, and conventional
      imaging modalities, such as CT or MRI, have been used in assessment of recurrence
      of cervical cancer after treatment. However, CT and MRI provide only anatomical
      data, which makes analysis of post-treatment change difficult. This study aims to
      explore the effectiveness of PET/CT, a new scanning device that combines PET and
      CT, in evaluation of cervical cancer lesions in patients with suspected
      recurrence. METHODS: We studied 51 patients suspected of recurrence among those
      who underwent F-18 FDG PET/CT for cervical cancer follow-up at Gachon University
      Gil Hospital between June 2006 and August 2009. Patients were considered to be at
      risk for recurrence if they reported symptoms that were clinically suggestive of
      recurrence, or if physical examination showed abnormalities, serum tumor marker
      levels rose, or follow-up images revealed changes, such as new lesions or
      swelling of previous sites. Sensitivity, accuracy, specificity, and positive and
      negative predictive values of PET/CT were measured. RESULTS: A total of 37
      patients were confirmed with recurrence or metastasis, 13 of whom were diagnosed
      histologically. Measured across all patients, PET/CT scored 97.3% on sensitivity,
      71.4% on specificity, a positive predictive value of 90%, a negative predictive
      value of 90.9%, and an accuracy of 90.2%. PET/CT yielded only one false negative
      diagnosis and four false positives. CONCLUSION: As F-18 FDG PET/CT has high
      sensitivity and negative predictive value in diagnosis of recurrent cervical
      cancers, it is expected that it will be useful for clinical determination of
      recurrence and prevention of unnecessary additional treatments. The hope is that
      a future study on a larger scale will contribute further to determination of the
      efficacy of PET/CT.

PMID- 24899991
TI  - Role of (18)F-FDG PET/CT, (123)I-MIBG SPECT, and CT in Restaging Patients
      Affected by Malignant Pheochromocytoma.
AB  - PURPOSE: Pheochromocytoma (PH) is a rare catecholamine-secreting tumor that
      arises from chromaffin tissue within the adrenal medulla and extra-adrenal sites;
      commonly it is sporadic, and malignant PH accounts for about 10% of all cases.
      Several imaging modalities have been used for the diagnosis and staging of this
      tumor: functional imaging using radio-labelled metaiodobenzylguanidine and, more
      recently, (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG
      PET/CT), which offers substantial sensitivity and specificity to correctly detect
      metastatic PH and helps to identify patients suitable for treatment with
      radiopharmaceuticals. The aim of our study was to compare CT, (18)F-FDG PET/CT,
      and (123)I-metaiodobenzylguanidine single photon emission tomography ((123)I-MIBG
      SPECT) as feasible methods to restage patients diagnosed histologically with PH.
      METHODS: We retrospectively evaluated 38 patients (27 females and 11 males; mean
      age: 44 +/- 15 years) with malignant PH documented histologically after surgical
      intervention. These patients underwent CT, (18)F-FDG PET/CT, and (123)I-MIBG
      SPECT. RESULTS: (18)F-FDG PET/CT showed positive results for neoplastic tissue in
      33/38 patients (86.8%) and negative in 5/38 (13.2%), in concordance with CT
      alone. (123)I-MIBG SPECT was positive in 30/38 patients (78,9%) and negative in
      8/38 (21.1%). No differences in lesion numbers were found between (18)F-FDG
      PET/CT and CT, whereas a difference could be demonstrated between (18)F-FDG
      PET/CT and (123)I-MIBG SPECT. CONCLUSION: (18)F-FDG PET/CT could more accurately
      restage patients with PH than CT and (123)I-MIBG SPECT, also in the absence of a
      staging study.

PMID- 24899992
TI  - FDG-PET/CT Is Superior to Enhanced CT in Detecting Recurrent Subcentimeter
      Lesions in the Abdominopelvic Cavity in Colorectal Cancer.
AB  - PURPOSE: This study aims to compare the performance of contrast-enhanced computed
      tomography (CeCT) and 18 F-fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG PET/CT) in detecting small tumor implants and
      metastatic lymph nodes (LNs) in the abdominopelvic cavity in patients with
      colorectal cancer. METHODS: We enrolled 16 patients who were clinically suspected
      of experiencing a recurrence (6 male, 10 female; mean age 61 +/- 14 years). All
      subjects underwent CeCT and PET/CT, and the performance of these methods was
      compared with regard to detecting recurrences. The final diagnosis of a
      recurrence was made clinically. RESULTS: CeCT identified 38 lesions in 12
      patients, all of which were detected by PET/CT. PET/CT found 27 additional
      lesions in 8 patients, comprising 9 seeding nodules (2 in the right upper
      quadrant of the abdomen and 7 in the pelvic cavity) and 18 LNs (2 celiac, 2
      paraaortic, 2 hepatic hilar, 11 common iliac, 1 external iliac). Most additional
      lesions were located in the pelvic cavity (approximately 78% of seeding nodules
      and 67% of lymph nodes). The maximum standardized uptake value (SUVmax) of the
      additional seeding nodules that were detected solely by PET/CT was significantly
      higher compared with the CeCT- and PET/CT-confirmed nodules (5.5 +/- 4.2 vs. 2.9
      +/- 2.5, p = 0.03). The seeding nodules that were detected only by PET/CT were
      significantly smaller than the CeCT- and PET/CT-confirmed nodules (long axis: 1.0
      +/- 0.3 cm vs. 2.0 +/- 1.1 cm, p = 0.001; short axis: 0.8 +/- 0.3 cm vs. 1.4 +/-
      0.8 cm, p = 0.004; mean of both axes: 0.9 +/- 0.3 cm vs. 1.7 +/- 0.9 cm, p =
      0.001). Similarly, PET/CT-only-detected LNs were significantly smaller than CeCT-
      and PET/CT-identified LNs (0.7 +/- 0.1 cm vs. 2.3 +/- 1.2 cm, p < 0.0001).
      CONCLUSION: PET/CT is superior to CeCT in detecting seeding nodules and
      metastatic LNs in patients with recurrent colorectal cancer. Specifically, PET/CT
      detects subcentimeter lesions in anatomically deformed pelvic cavities.

PMID- 24899993
TI  - Intratumoral Heterogeneous F-18 Fluorodeoxyglucose Uptake Corresponds with
      Glucose Transporter-1 and Ki-67 Expression in a Case of Krukenberg Tumor:
      Localization of Intratumoral Hypermetabolic Focus by Fused PET/MR Image.
AB  - The expression of glucose transporters (Glut-1, Glut-3), hexokinase-II, and Ki-67
      has been proposed to explain intratumoral heterogeneous F-18 fluorodeoxyglucose
      (FDG) uptake. We report a case of Krukenberg tumor with intratumoral
      heterogeneous FDG uptake which corresponded well with the expression levels of
      Glut-1 and ki-67. Fused positron emission tomography (PET)/magnetic resonance
      (MR) imaging was helpful for localizing the metabolically active area in the
      tumor specimen. This report elucidates the relationship between the intratumoral
      heterogeneous FDG uptake and biologic heterogeneity, and shows the usefulness of
      PET/MR in research on intratumoral heterogeneity. 

PMID- 24899994
TI  - Nonfunctioning Periurethral Paraganglioma Incidentally Detected by FDG PET/CT.
AB  - Paragangliomas are extra-adrenal neuroendocrine tumors that are derived from
      neural crest cells. Among all the paragangliomas, those in a pelvic location are
      extremely rare. In addition, the prevalence of nonfunctioning paragangliomas is
      underestimated because of their clinical latency, and they are often
      underdiagnosed unless they cause symptoms. We report a case of a nonfunctioning
      periurethral paraganglioma that was incidentally detected by FDG PET/CT during
      regular follow-up after excision of a melanoma on the left thumb. 

PMID- 24899995
TI  - Detection of Thyroid Metastasis of Renal Transitional Cell Carcinoma Using FDG
      PET/CT.
AB  - A 69-year-old man who was diagnosed with renal transitional cell carcinoma (TCC)
      underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography with
      computed tomography (PET/CT) for detecting recurrence after chemotherapy. FDG
      PET/CT revealed multiple new hypermetabolic lesions in many places, including the
      right thyroid gland. Biopsy of the thyroid lesion was performed, and a diagnosis
      of metastatic TCC was made. We could detect thyroid metastasis of renal TCC by
      FDG PET/CT. 

PMID- 24899996
TI  - (18)F-FDG PET/CT Findings in a Breast Cancer Patient with Concomitant Tuberculous
      Axillary Lymphadenitis.
AB  - Although (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)
      is a sensitive modality for detecting a malignant lesion, increased (18)F-FDG
      uptake is also seen in infected or inflammatory processes. Here, we report the
      case of a breast cancer patient with concomitant tuberculous axillary
      lymphadenitis that showed increased (18)F-FDG uptake. A 39-year-old woman
      underwent preoperative (18)F-FDG PET/computed tomography (CT) as a part of the
      work-up for right breast cancer. (18)F-FDG PET/CT images showed a malignant
      lesion in the right breast with moderate (18)F-FDG uptake, and multiple enlarged
      right axillary lymph nodes with intense (18)F-FDG uptake. Subsequently, the
      patient underwent right mastectomy and right axillary lymph node dissection.
      Histopathological examination confirmed breast cancer and tuberculous
      lymphadenitis, and the patient was treated concomitantly with anti-tuberculous
      therapy. 

PMID- 24899997
TI  - F-18 FDG PET/CT Findings of Spontaneous Mesenteric Fibromatosis in a Patient with
      Gardner's Syndrome.

PMID- 24899998
TI  - Incidental Detection of Temporary Focal FDG Retention in the Spleen.

PMID- 24899999
TI  - Evaluation of Salivary Gland Dysfunction Using Salivary Gland Scintigraphy in
      Sjogren's Syndrome Patients and in Thyroid Cancer Patients after Radioactive
      Iodine Therapy.
AB  - PURPOSE: Salivary gland scintigraphy (SGS) provides an objective means of
      diagnosing salivary gland dysfunction in Sjogren's syndrome (SS) patients and in
      thyroid cancer patients after radioactive iodine (RAI) therapy. In the present
      study, SGS was performed in SS patients and in thyroid cancer patients post-RAI,
      and scintigraphic parameters were compared. METHODS: Twenty-eight SS patients
      (males:females = 1:27, age 53.3 +/- 11.9 years), 28 controls (males:females =
      3:25, age 54.1 +/- 10.1 years), and 92 thyroid cancer patients (males:females =
      28:64, age 46.2 +/- 12.9) who had undergone a session of high-dose RAI therapy
      (mean dose, 5.2 +/- 1.5 GBq) were included. SGS was performed using Tc-99m
      pertechnetate (925 MBq). Scintigraphic parameters (parotid uptake ratio PU,
      submandibular uptake ratio SU, percentage parotid excretion %PE, and percentage
      submandibular excretion %SE) were measured and compared for SS, thyroid cancer
      post-RAI, and control patients. RESULTS: PU, SU, %SE, and %PE were all
      significantly lower in SS than in post-RAI thyroid cancer or control patients (p
      < 0.05), whereas only %PE was significantly lower in post-RAI thyroid cancer
      patients than in controls (p < 0.05). SU and %SE were found to be correlated with
      the unstimulated whole salivary flow rate. CONCLUSION: Scintigraphic parameters
      derived from SGS can play a crucial role in the detection of salivary gland
      dysfunction in SS patients and in post-RAI thyroid cancer patients.

PMID- 24900000
TI  - Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F-18 FDG
      Administration as Effective Alternatives to Intravenous Administration in Mouse
      Tumor Models Using Small Animal PET/CT Studies.
AB  - PURPOSE: We compared alternative routes for (18)F-fluorodeoxyglucose (FDG)
      administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral
      (PO) routes, with the intravenous (IV) route in normal tissues and tumors of
      mice. MATERIALS AND METHODS: CRL-1642 (ATCC, Lewis lung carcinoma) cells were
      inoculated in female BALB/c-nu/nu mice 6 to 10 weeks old. When the tumor grew to
      about 9 mm in diameter, positron emission tomography (PET) scans were performed
      after FDG administration via the RO, IP, PO or IV route. Additional serial PET
      scans were performed using the RO, IV or IP route alternatively from 5 to 29 days
      after the tumor cell injection. RESULTS: There was no significant difference in
      the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP
      and IV routes. PO administration, however, showed delayed distribution and
      unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar
      temporal pattern and increased until 60 min after FDG administration in the RO,
      IP and IV injection groups. In the PO administration group, tumoral uptake was
      delayed and reduced. There was no statistical difference among the RO, IP and IV
      administration groups for additional serial PET scans. CONCLUSION: RO
      administration is an effective alternative route to IV administration for mouse
      FDG PET scans using normal mice and tumor models. In addition, IP administration
      can be a practical alternative in the late phase, although the initial uptake is
      lower than those in the IV and RO groups.

PMID- 24900001
TI  - The Clinical Usefulness of (18)F-FDG PET/CT in Patients with Systemic Autoimmune
      Disease.
AB  - PURPOSE: Individuals with systemic autoimmune disease have an increased
      susceptibility to both inflammation and malignancy. The aim of this study was to
      evaluate the clinical usefulness of (18)F-FDG PET/CT in patients with systemic
      autoimmune disease. METHODS: Forty patients diagnosed with systemic autoimmune
      disease were enrolled. Diagnostic accuracy of FDG PET/CT for detecting malignancy
      was assessed. FDG PET/CT findings, including maximum standardized uptake (SUVmax)
      of lymphadenopathy (LAP), liver, bone marrow, spleen, joint and muscles, were
      considered for the characterization of LAPs. RESULTS: FDG PET/CT could detect
      metabolically activated lesions in 36 out of 40 patients (90%) including
      inflammatory lesions in 28 out of 32 patients (88%). The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of FDG PET/CT for the detection of malignancy were 100, 67, 70, 25, and 100%,
      respectively. Multiple LAPs were found in 25 of 40 patients (63%), and comprised
      three malignancies, four cases of tuberculosis, and 18 reactive changes. A SUVmax
      ratio of bone marrow to liver below 0.78 could distinguish malignancy from
      tuberculosis + reactive change (AUC = 1.000, sensitivity: 100%, specificity:
      100%). The SUVmax ratio of spleen to liver in the reactive group was also
      significantly higher than that in the malignancy group (P = 0.014). SUVmax of LAP
      in the TB group was significantly higher than that in the reactive group (P =
      0.040). CONCLUSIONS: PET/CT is useful in detecting and differentiating
      inflammation and malignancy in patients with systemic autoimmune disease.
      Frequent false-positive interpretations can be minimized by consideration of FDG
      uptake in bone marrow and spleen.

PMID- 24900002
TI  - Impact of Lymphoid Follicles and Histiocytes on the False-Positive FDG Uptake of
      Lymph Nodes in Non-Small Cell Lung Cancer.
AB  - PURPOSE: Although (18)F-fluorodeoxyglucose (FDG) PET/CT has improved the accuracy
      of evaluating lymph node (LN) staging in non-small cell lung cancer (NSCLC),
      false-positive results remain a problem. The reason why benign LNs show high FDG
      uptake is still unclear. The aim of this study was to identify molecular and
      pathological characteristics of benign LNs showing high FDG uptake. MATERIALS AND
      METHODS: We studied 108 mediastinal LNs of pathologically benign nature obtained
      from 43 patients with NSCLC who underwent FDG PET/CT and surgery. We measured the
      following parameters in each LN: maximum standardized uptake value (maxSUV),
      short diameter, maximum Hounsfield unit (maxHU) value, occupied proportions of
      lymphoid follicles, histiocytes in extrafollicular space and the degree of
      glucose transporter 1 (Glut1) expression. We compared the parameters between two
      LN groups according to maxSUV. RESULTS: There were 74 LNs showing maxSUV>=3.0
      (group 1) and 34 LNs with maxSUV<3.0 (group 2). The size of LN (p < 0.001) and
      maxHU (p = 0.003) in group 1 was higher than that in group 2. Histologically, the
      occupied proportions of lymphoid follicles (p = 0.031) or histiocytes (p = 0.004)
      were higher in group 1. The Glut1 expression of lymphoid follicles (p = 0.035) or
      histiocytes (p = 0.005) was also higher in group 1. CONCLUSION: Lymphoid
      follicular hyperplasia and histiocyte infiltration associated with Glut1
      overexpression are important molecular and pathological mechanisms for false
      positive FDG uptake in benign mediastinal LNs in patients with NSCLC.

PMID- 24900003
TI  - Incidental Focal (18)F-FDG Uptake in the Prostate: Clinical Significance and
      Differential Diagnostic Criteria.
AB  - PURPOSE: The extent and intensity of (18)F-FDG uptake in prostate cancer patients
      are known to be variable, and the clinical significance of focal (18)F
      fluorodeoxyglucose ((18)F-FDG) uptake that is incidentally found on positron
      emission tomography (PET) has not been established. We investigated the clinical
      significance of incidental focal prostate uptake of (18)F-FDG on PET/computed
      tomography (CT) and analyzed differential findings on PET/CT between malignant
      and benign uptake. METHODS: A total of 14,854 whole-body (18)F-FDG PET/CT scans
      (4,806 that were conducted during cancer screening and 10,048 that were conducted
      to evaluate suspected or alleged cancer outside of the prostate) were
      retrospectively reviewed to determine the presence, location, multiplicity and
      maximum standardized uptake value (SUVmax) of focal prostate uptake and combined
      calcification. The final diagnosis determined by serum prostate-specific antigen
      (PSA) level and biopsy was compared with PET findings. RESULTS: Incidental focal
      prostate uptake was observed in 148 of 14,854 scans (1.0 %). Sixty-seven of these
      148 subjects who had diagnostic confirmation were selected for further analysis.
      Prostate cancer was diagnosed in nine of 67 subjects (13.4%). The remaining 58
      subjects had no malignancy in the prostate based on normal serum PSA level (n =
      53), or elevated serum PSA level with a negative biopsy result (n = 5). While
      84.6% (11/13) of malignant uptake was peripherally located in the prostate
      glands, 60.2% (50/83) of benign uptake was centrally located (p < 0.05). The
      positive predictive value of peripheral focal uptake for malignancy was 25%. The
      SUVmax, multiplicity and combined calcification were not significantly different
      between the two groups. CONCLUSION: Although incidental focal (18)F-FDG uptake in
      the prostate is not common, the incidence of cancer with focal uptake is not low.
      Therefore, these findings deserve further evaluation. The location of the focal
      prostate uptake may help with the selection of high-risk prostate cancer
      patients.

PMID- 24900004
TI  - Clinical Significance of Diffuse (18)F-FDG Uptake in Residual Thyroid Gland after
      Unilateral Thyroid Lobectomy.
AB  - PURPOSE: We investigated the clinical significance of diffuse uptake in remaining
      thyroid after unilateral lobectomy for thyroid cancer. METHODS: A total of 144
      thyroid cancer patients who underwent (18)F-FDG PET/CT after lobectomy were
      enrolled in the present study. The PET/CT images were evaluated for the presence
      of diffuse (18)F-FDG uptake with maximum SUV (SUVmax) >2.0 in the residual
      thyroid and placed into one of two groups: with diffuse uptake and without
      diffuse uptake group. Clinical, laboratory, and PET/CT parameters in both groups
      were compared. Correlations between SUVmax of thyroid and available parameters
      were analyzed. RESULTS: Forty-two of 144 patients (29.2%) had diffuse thyroid
      uptake (mean SUVmax: 3.2 +/- 1.1). All patients with diffuse uptake and 96
      (94.1%) without diffuse uptake were receiving thyroxine therapy (P = 0.09).
      Thyroid function tests showed that most patients were euthyroid status (78.6 vs.
      85.3%, P = 0.36). TgAb levels were significantly higher in patients with diffuse
      uptake (338.0 +/- 664.6 vs. 57.3 +/- 46.4, P < 0.0001). Mean attenuation values
      in the diffuse uptake group were significantly lower (72.2 +/- 15. vs. 97.0 +/-
      16.0, P < 0.0001). An inverse correlation was found between SUVmax and mean
      attenuation values of residual thyroid in all patients (r = -0.57, P < 0.0001)
      and subgroup with diffuse uptake (r = -0.31, P < 0.05). CONCLUSION: In this
      study, diffuse (18)F-FDG uptake in the residual thyroid after unilateral
      lobectomy was a relatively frequent finding and may be associated with chronic
      thyroiditis. This uptake is not influenced by thyroid status or thyroxine
      therapy. The (18)F-FDG uptake is inversely correlated with mean attenuation value
      of thyroid.

PMID- 24900005
TI  - Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using (18)F-FDG
      PET/CT and (99m)Tc-HDP Bone Scintigraphy: Characteristics of Soft Tissue
      Formation.
AB  - PURPOSE: Bone metastasis from hepatocellular carcinoma (HCC) can present with
      soft tissue formation, resulting in oncologic emergency. Contrast-enhanced FDG
      PET/CT and bone scintigraphy were compared to evaluate characteristics of bone
      metastases with or without soft tissue formation from HCC. METHODS: Of 4,151
      patients with HCC, 263 patients had bone metastases. Eighty-five patients with
      bone metastasis from HCC underwent contrast-enhanced FDG PET/CT. Fifty-four of
      the enrolled subjects had recent (99m)Tc-HDP bone scintigraphy available for
      comparison. Metastatic bone lesions were identified with visual inspection on FDG
      PET/CT, and maximum standardized uptake value (SUVmax) was used for the
      quantitative analysis. Confirmation of bone metastasis was based on
      histopathology, combined imaging modalities, or serial follow-up studies.
      RESULTS: Forty-seven patients (55%) presented with soft tissue formation, while
      the remaining 38 patients presented without soft tissue formation. Frequent sites
      of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage
      (14%). The soft-tissue-formation group had more frequent bone pain (77 vs. 37%, p
      < 0.0001), higher SUVmax (6.02 vs. 3.52, p < 0.007), and higher incidence of
      photon defect in bone scintigraphy (75 vs. 0%) compared to the non-soft-tissue
      formation group. FDG PET/CT had higher detection rate for bone metastasis than
      bone scintigraphy both in lesion-based analysis (98 vs. 53%, p = 0.0015) and in
      patient-based analysis (100 vs. 80%, p < 0 .001). CONCLUSIONS: Bone metastasis
      from HCC showed a high incidence of soft tissue formation requiring emergency
      treatment. Although the characteristic findings for soft tissue formation such as
      photon defect in bone scintigraphy are helpful in detection, overall
      detectability of bone metastasis is higher in FDG PET/CT. Contrast-enhanced
      PET/CT will be useful in finding and delineating soft-tissue-forming bone
      metastasis from HCC.

PMID- 24900007
TI  - Assessment of Therapeutic Effect of Sunitinib by (11)C-Acetate PET Compared with
      FDG PET Imaging in a Patient with Metastatic Renal Cell Carcinoma.
AB  - Although sunitinib shows a high response rate in patients with untreated
      metastatic renal cell carcinoma (mRCC), quite a few patients show no therapeutic
      effect. Therefore, it is crucial to distinguish the patients who respond to
      sunitinib from those who do not as early as possible after the administration of
      the therapy. We herein report a case of mRCC in which (11)C-acetate (AC) positron
      emission tomography (PET) showed an early therapeutic effect of sunitinib
      treatment 4 weeks after its administration. 

PMID- 24900006
TI  - SPECT/CT in the Diagnosis of Skull Base Osteomyelitis.
AB  - Skull base osteomyelitis is a potentially fatal disease. We demonstrate here the
      utility of SPECT/CT in diagnosing this entity, which was not obvious on a planar
      bone scan. A (99m)Tc MDP bone scan with SPECT/CT was carried out on a patient
      with clinically suspected skull base osteomyelitis. Findings were correlated with
      contrast-enhanced CT (CECT) and MRI. Planar images were equivocal, but SPECT/CT
      showed intense uptake in the body of sphenoid and petrous temporal bone as well
      as the atlas corresponding to irregular bone destruction on CT and MRI. These
      findings indicate that SPECT/CT may have an additional role beyond planar imaging
      in the detection of skull base osteomyelitis. 

PMID- 24900008
TI  - Necrotizing Cervical Lymphadenitis Caused by Mycobacterium simiae in an HIV
      Positive Patient: Imaging with (18)F-FDG PET/CT.
AB  - Mycobacterium simiae (M. simiae) is an opportunistic pathogen rarely associated
      with human disease, although in recent years M. simiae has been detected with
      increasing frequency in human immunodeficiency virus (HIV)-infected patients,
      usually causing disseminated infection with fever, diarrhea and weight loss. We
      report the case of an HIV-positive man, who was referred for an (18)F-FDG PET/CT
      to evaluate a solitary pulmonary nodule. The PET/CT showed incidental large
      necrotic cervical lymph nodes, compatible with necrotizing cervical
      lymphadenitis. Biopsy and culture of one of the affected lymph nodes were
      positive for M. simiae. We present the first report of (18)F-FDG PET/CT imaging
      of an infectious process caused by M. simiae in humans. 

PMID- 24900009
TI  - Bilateral Tubo-Ovarian Abscess Mimics Ovarian Cancer on MRI and (18)F-FDG PET/CT.
AB  - A 20-year-old woman, who presented with a several-week history of abdominal pain,
      was referred for magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose
      (FDG) positron emission tomography (PET)/computed tomography (CT) after an
      ultrasound showed complex cystic masses arising from both ovaries. The MRI and
      (18)F-FDG PET/CT imaging characteristics of the ovarian masses were strongly
      suspicious for malignancy, and the masses were surgically removed.
      Histopathological evaluation revealed a bilateral tubo-ovarian abscess, with no
      evidence of malignancy. This case highlights a potentially serious pitfall in the
      evaluation of suspicious pelvic masses by (18)F-FDG PET/CT, whereby a complex
      bilateral tubo-ovarian abscess may mimic the PET/CT imaging characteristics of an
      ovarian or pelvic malignancy. 

PMID- 24900010
TI  - A Case of Meigs' Syndrome: The (18)F-FDG PET/CT Findings.
AB  - The findings of an ovarian mass with marked ascites and pleural effusion are
      highly suggestive of malignancy, especially in a postmenopausal female with an
      elevated level of CA-125. However, benign conditions such as Meigs' syndrome
      should be considered in the differential diagnosis if the primary mass shows
      benign features. (18)F-FDG is known to be useful to differentiate between
      malignant and benign diseases, and this utility is also promising in the case of
      ovarian tumor. We present here a case of Meigs' syndrome that was evaluated by
      (18)F-FDG PET/CT, and this helped the preoperative diagnosis be made. (18)F-FDG
      PET/CT is a promising modality to diagnose the pathological character of an
      ovarian tumor preoperatively, which can lead to a proper therapeutic plan. 

PMID- 24900011
TI  - Using (18)F-FDG PET/CT to Detect an Occult Mesenchymal Tumor Causing Oncogenic
      Osteomalacia.
AB  - Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by renal
      phosphate excretion, hypophosphatemia, and osteomalacia. This syndrome is often
      caused by tumors of mesenchymal origin. Patients with oncogenic osteomalacia have
      abnormal bone mineralization, resulting in a high frequency of fractures. Tumor
      resection is the treatment of choice, as it will often correct the metabolic
      imbalance. Although oncogenic osteomalacia is a potentially curable disease,
      diagnosis is difficult and often delayed because of the small size and sporadic
      location of the tumor. Bone scintigraphy and radiography best characterize
      osteomalacia; magnetic resonance imaging findings are nonspecific. Here, we
      report a case of oncogenic osteomalacia secondary to a phosphaturic mesenchymal
      tumor that was successfully detected by (18)F-fluorodeoxyglucose positron
      emission tomography/computed tomography ((18)F-FDG PET/CT). This case illustrates
      the advantages of (18)F-FDG PET/CT in detecting the occult mesenchymal tumor that
      causes oncogenic osteomalacia. 

PMID- 24900012
TI  - F-18 FDG PET/CT of a Gastric Schwannoma.

PMID- 24900014
TI  - Radiosynthesis of (99m)Tc(CO)3-Clinafloxacin Dithiocarbamate and Its Biological
      Evaluation as a Potential Staphylococcus aureus Infection Radiotracer.
AB  - BACKGROUND: Clinafloxacin dithiocarbamate (CNND) was radiolabeled with technetium
      99m ((99m)Tc) using [(99m)Tc(CO)3(H2O)3](+) and assessed for its radiochemical
      stability in saline and serum, its in vitro binding with methicillin-resistant
      Staphylococcus aureus (MRSA) and biodistribution in female nude mice (FNM)
      artificially infected with live and heat-killed MRSA. METHODS: In normal saline
      (NS) the (99m)Tc(CO)3-clinafloxacin dithiocarbamate ((99m)Tc(CO)3-CNND) showed
      radiochemical stability with a maximum value of 99.10 +/- 0.20% and remained
      stable up to 4 h (92.65 +/- 0.18%). RESULTS: In human serum at 37 degrees C
      within 16 h of incubation, 14.85% side products as a result of de-tagging
      developed. Incubation with MRSA gave saturated binding with a maximum value of
      72.75 +/- 1.20%. Almost six-fold higher uptake was seen in the infected muscle of
      the FNM as compared to the inflamed and normal muscle. The (99m)Tc(CO)3-CNND
      complex showed a normal route of excretion from the body of the FNM model.
      CONCLUSION: The higher stability in NS, HS, saturated in vitro binding with a
      live strain of MRSA and six-fold higher uptake in the target organ showed the
      (99m)Tc(CO)3-CNND complex to be a potential MRSA infection radiotracer.

PMID- 24900013
TI  - Alternative medical treatment for radioiodine-refractory thyroid cancers.
AB  - Thyroid cancer is one of the most rapidly increasing cancers in many countries.
      Although most thyroid cancers are differentiated cancers and easily treated with
      radioiodine (RI), a portion of differentiated and undifferentiated cancers is
      refractory not only to RI therapy, but also to radiotherapy and chemotherapy.
      Thus, various alternative therapies have been tested in RI-refractory thyroid
      cancers. These alternative therapies include two major categories:
      redifferentiation therapy and recent molecular target therapy. Several clinical
      trials have investigated these therapies. They demonstrated potential effects of
      the therapies, although the results have been somewhat limited so far. Thus, the
      future strategy for undifferentiated thyroid cancers will involve individualized,
      lesion-specific, and combined therapy. In this review, the basic mechanism of
      each redifferentiation and molecular target therapy is discussed, and results of
      recent clinical trials using these therapeutic agents are summarized. 

PMID- 24900015
TI  - Clinical Significance of F-18 FP-CIT Dual Time Point PET Imaging in Idiopathic
      Parkinson's Disease.
AB  - PURPOSE: The purpose of this study was to investigate the diagnostic value of
      dual time point F-18 FP-CIT PET imaging in idiopathic Parkinson's disease (PD).
      MATERIALS AND METHODS: Twenty-four patients with PD (mean age 69.6) and 18
      healthy people (mean age 70.26) underwent two sequential PET/CT scans (dual time
      point imaging) at 90 and 210 min after F-18 FP-CIT injection. Tracer activity of
      region of interest was measured in the caudate, putamen and a reference region in
      the brain from both time points. The outcome parameter was the striatooccipital
      ratio (SOR). Normal SOR values were obtained in the control group. The percent
      change in tracer activity between 90- and 210-min images was calculated. The SOR
      values and the percent change in tracer activity were compared between the
      patients and healthy control group. RESULTS: The SOR values for the caudate,
      anterior and posterior putamen at both 90- and 210-min images were significantly
      reduced in the patients with PD. The lowest P value was obtained for the anterior
      and posterior putamen (p < 0.001) at both time points. There were significant
      differences of the percent change in tracer activity for the anterior and
      posterior putamen in the two groups (p = 0.01). CONCLUSIONS: F-18 FP-CIT PET
      scans at 90 and 210 min after injection are both able to diagnose PD. Therefore,
      the 90-min image by itself is sufficient for diagnosing PD.

PMID- 24900016
TI  - Diagnostic performance of three-phase bone scan for complex regional pain
      syndrome type 1 with optimally modified image criteria.
AB  - PURPOSE: Although the three-phase bone scan (TBPS) is one of the widely used
      imaging studies for diagnosing complex regional pain syndrome type I (CRPS-1),
      there is some controversy regarding the TPBS image criteria for CRPS-1. In this
      study, we modified the image criteria using image pattern and quantitative
      analysis in the patients diagnosed using the most recent consensus clinical
      diagnostic criteria. MATERIALS AND METHODS: The study included 140 patients with
      suspected CRPS-1 (CRPS-1, n = 79; non-CRPS, n = 61; mean age 39 +/- 15 years) who
      underwent TPBS. The clinical diagnostic criteria for CRPS-1 revised by the
      Budapest consensus group were used for confirmative diagnosis. Patients were
      classified according to flow/pool and delayed uptake (DU) image patterns, and the
      time interval between the initiating event and TPBS (TIevent-scan). Quantitative
      analysis for lesion-to-contralateral ratio (LCR) was performed. Modified TPBS
      image criteria were created and evaluated for optimal diagnostic performance.
      RESULTS: Both increased and decreased periarticular DU were significant image
      findings for CRPS-1 (CRPS-1 positive-rate = 73% in the increased DU group, 75% in
      the decreased DU group). The TIevent-scan did not differ significantly between
      the different image pattern groups. Quantitative analysis revealed an LCR of 1.43
      was the optimal cutoff value for CRPS-1 and diagnostic performance was
      significantly improved in the increased DU group (area under the curve = 0.732).
      Given the modified image criteria, the sensitivity and specificity of TPBS for
      diagnosing CRPS-1 were 80% and 72%, respectively. CONCLUSIONS: Optimally modified
      TPBS image criteria for CRPS-1 were suggested using image pattern and
      quantitative analysis. With the criteria, TPBS is an effective imaging study for
      CRPS-1 even with the most recent consensus clinical diagnostic criteria.

PMID- 24900017
TI  - Whole-Body Bone Scan Findings after High-Intensity Focused Ultrasound (HIFU)
      Treatment.
AB  - PURPOSE: This study aims to examine the findings of (99m)Tc-diphosphonate bone
      scans in cancer patients with a history of HIFU treatment. METHODS: Bone scan
      images of patients with a history of HIFU treatment for primary or metastatic
      cancer from January 2006 to July 2010 were retrospectively reviewed. Cases of
      primary bone tumor or HIFU treatment reaching only the superficial soft tissue
      layer were excluded. RESULTS: Bone scan images of 62 patients (26 female, 36
      male; mean age 57 +/- 9 years) were studied. HIFU treatment was performed in the
      liver (n = 40), pancreas (n = 16), and breast (n = 6). Mean interval time between
      HIFU treatment and bone scan was 106 +/- 105 days (range: 1-572 days). Of 62
      scans, 43 showed diffusely decreased uptake of bone within the path of HIFU
      treatment: antero-axillary and/or posterior arcs of right 5th to 11th ribs in 34
      cases after treatment of hepatic lesions; anterior arcs of 2nd to 5th ribs in 5
      cases after treatment for breast tumors; and posterior arcs of left 9th to 11th
      ribs or thoraco-lumbar vertebrae in 4 cases after treatment for pancreas tumor.
      Of 20 patients who had bone scans more than twice, five showed recovered uptake
      of the radiotracer in the involved ribs in the follow-up bone scan. CONCLUSION:
      Of 62 bone scans in patients with a history of HIFU treatment for primary or
      metastatic cancer, 69% presented diffusely decreased uptake in the bone in the
      path of HIFU treatment.

PMID- 24900018
TI  - Differential findings of tc-99m sestamibi dual-phase parathyroid scintigraphy
      between benign and malignant parathyroid lesions in patients with primary
      hyperparathyroidism.
AB  - PURPOSE: This study aimed to investigate the differential findings in clinical
      and biochemical features, and Tc-99m sestamibi (MIBI) dual-phase parathyroid
      scintigraphy for malignant and benign parathyroid lesions in patients with
      primary hyperparathyroidism. METHODS: Subjects were 102 parathyroid lesions from
      91 patients with primary hyperparathyroidism. Scintigraphic findings included
      radioactivity grade, uptake pattern, uptake contour, lesion size on early and
      delayed images, and degree of washout. Clinical and biochemical features were
      also evaluated. Histopathology confirmed the final diagnosis for all the
      patients. RESULTS: Final diagnoses were 94 benign parathyroid lesions and 8
      parathyroid carcinomas. The patients with parathyroid carcinoma were
      significantly older (p = 0.002) and had significantly higher serum parathyroid
      hormone concentrations than those with benign parathyroid lesions (p < 0.001).
      All malignant parathyroid lesions showed intense radioactivity similar to or
      greater than the submandibular gland activity on delayed images (p = 0.007), and
      little radioactivity difference between early and delayed images (p = 0.012). The
      cancer incidence for parathyroid lesions with both intense radioactivity and no
      washout was 17.0% (8/47). When parathyroid lesions with all of the above
      mentioned findings were regarded as malignant, the cancer incidence significantly
      increased from 17.0% to 33.3% (8/24, p < 0.001). CONCLUSION: For Tc-99m MIBI dual
      phase parathyroid scintigraphy, uptake grade on delayed images and washout were
      significantly useful diagnostic criteria for differentiating benign from
      malignant parathyroid lesions, along with age and parathyroid hormone serum
      concentration.

PMID- 24900019
TI  - Significance of SUV on Follow-up F-18 FDG PET at the Anastomotic Site of
      Gastroduodenostomy after Distal Subtotal Gastrectomy in Patients with Gastric
      Cancer.
AB  - PURPOSE: The aim of this study was to characterize the patterns of
      fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography/computed
      tomography (FDG PET/CT) at the anastomotic site of gastroduodenostomy after
      distal subtotal gastrectomy in patients with gastric cancer. METHODS: From May
      2007 to May 2010, two or more follow-up measurements using FDG PET/CT scans were
      done for 19 patients (11 men, 8 women; mean age, 62.0 +/- 10.3 years) who
      underwent distal subtotal gastrectomy with gastroduodenostomy between February
      2006 and March 2008 for detecting gastric cancer recurrence at our medical
      center. The FDG PET/CT images were retrospectively reviewed. Patients with local
      recurrence, regional nodal metastasis or distant metastasis on follow-up studies
      were excluded. CT and endoscopy were done within 1 month before or after the FDG
      PET/CT scan. Eight patients had two follow-ups of FDG PET/CT, and 11 patients had
      three follow-ups. The mean interval between surgery and the first follow-up FDG
      PET/CT was 12.9 +/- 0.8 months (n = 19); between the first and second it was 12.3
      +/- 1.0 months (n = 19); between the second and third it was 11.6 +/- 0.7 months
      (n = 11). The F-18 FDG uptakes at the anastomotic site and fundus in the remnant
      stomach were measured by maximum standardized uptake value (SUVmax) using a
      region of interest technique. RESULTS: The SUVmax at the anastomotic site was
      significantly higher than that of the fundus on all series of first, second and
      third follow-up studies (3.3 +/- 1.1 vs. 2.1 +/- 0.7, p < 0.001: 3.1 +/- 0.9 vs.
      2.2 +/- 0.7, p = 0.001: 3.0 +/- 0.6 vs. 2.1 +/- 0.7, p = 0.006, respectively).
      The SUVmax for the anastomotic site and fundus, and SUVmax ratio for the
      anastomotic site over the fundus were not significantly different throughout the
      series. CONCLUSION: The SUVmax at the anastomotic site is significantly higher
      than that of the fundus and does not decrease significantly over time. Therefore,
      the local recurrence of gastric cancer after surgery could not be definitely
      differentiated from physiologic uptake or postoperative inflammatory change.

PMID- 24900020
TI  - (18)F-FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones,
      and Vasectomy.
AB  - PURPOSE: The purpose of this study was to evaluate glucose metabolism of normal
      human testis on (18)F-FDG PET/CT and to assess possible correlations among age,
      the serum levels of sex hormones, and vasectomy. METHODS: (18)F-FDG PET/CT was
      performed in 66 normal healthy men (50.8 +/- 13.6 years, range 22-81), and mean
      standard uptake values (SUV) of (18)F-FDG in testis and adductor muscle were
      measured. Testis-muscle SUV ratios (T/M ratios) were calculated. Serum levels of
      total testosterone, free testosterone, estradiol, and of sex-hormone binding
      globulin (SHBG) were measured. We searched for correlations between T/M ratios
      and age and the serum concentrations of sex hormones. (18)F-FDG PET/CT was also
      performed in 32 vasectomized men (55.7 +/- 7.8 years, range 38-71) and 52
      nonvasectomized men (55.4 +/- 11.6 years, range 37-72). Mean SUVs of testis and
      adductor muscle were measured, and T/M ratios were calculated. RESULTS: A
      significant age-related decline was found in T/M ratio (r = -0.509, p < 0.0001).
      Serum levels of total testosterone and free testosterone were also found to be
      positively correlated with T/M ratio (r = 0.427, p = 0.0003; r = 0.435, p =
      0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were
      significantly lower than those of nonvasectomized men (p < 0.0378 and p = 0.0001,
      respectively). CONCLUSIONS: Glucose metabolism in the testis in an adult
      population was found to be correlated with age, serum sex hormone level, and
      vasectomy history. These results indicate that testicular (18)F-FDG uptake may
      have attributed to testicular function and testicular histology. Our findings may
      have important implications for the interpretation of testicular (18)F-FDG uptake
      in the normal adult population.

PMID- 24900021
TI  - Systemic Endoradiotherapy with Carrier-Added 4-[(131)I]Iodo-L-Phenylalanine:
      Clinical Proof-of-Principle in Refractory Glioma.
AB  - PURPOSE: To explore feasibility, tolerability, dosimetry and probable efficacy of
      intravenous endoradiotherapy with carrier-added 4-[(131)I]iodo-L-phenylalanine
      (c.a. (131)I-IPA) in refractory high-grade glioma. METHODS: Two male patients (45
      and 50 years), with long-standing, extensively pre-treated gliomas and evidence
      of progression underwent single intravenous injections of 2 and 4 GBq of c.a.
      (131)I-IPA, respectively. Tumour targeting was verified by (131)I-IPA single
      photon emission computed tomography (SPECT). Metabolic and morphological changes
      indicative of tumour response were assessed by sequential
      [(18)F]fluoroethyltyrosine ((18)F-FET) positron emission tomography (PET) and
      contrast-enhanced magnetic resonance imaging (MRI) following therapy. Further
      monitoring included clinical state, safety laboratory, quality of life and
      dosimetry. Absorbed mean organ and whole-body doses were determined according to
      the Medical Internal Radiation Dose (MIRD) scheme using OLINDAEXM based on serial
      planar scintigraphy. RESULTS: Both patients tolerated the treatment well. No
      evidence of acute or delayed organ toxicity was observed. (131)I-IPA accumulated
      in the tumour recurrences identified by MRI/(18)F-FET. In patient 1, PET showed
      progressively decreasing maximum standardised uptake values (SUVmax) over 10
      months, indicating metabolic response, paralleled by reduced contrast enhancement
      and tumour volume on MRI. Progression occurred 18 months after therapy. Treatment
      was repeated using 6.6 GBq of (131)I-IPA, to which no response was observed.
      Patient 2, followed-up for 3 months after therapy, showed stable disease on MRI
      and PET. Mean absorbed whole body doses ranged from 0.13 to 0.17 mSv/MBq, with
      the highest absorbed organ doses to kidneys, bladder and heart (0.86-1.23; 0.49
      0.6 and 0.45-0.56 mSv/MBq). CONCLUSION: Systemic endoradiotherapy using up to 6.6
      GBq of c.a.(131)I-IPA is not associated with clinically detectable toxicity.
      Measurable anti-tumour effects in gliomas were observed. (131)I-IPA warrants
      further evaluation as glioma therapy.

PMID- 24900022
TI  - Incidental Bilateral Renal Oncocytoma in a Patient with Metastatic Carcinoma of
      Unknown Primary: a Pitfall on (18)F-FDG PET/CT.
AB  - Bilateral renal masses are uncommon but can raise a strong suspicion of primary
      or secondary malignancy, especially during the initial work-up of an oncology
      patient. Renal oncocytomas are benign renal tumors that are commonly discovered
      incidentally on diagnostic imaging with a small percentage occurring bilaterally.
      Although (18)F-FDG uptake in renal oncocytomas has been described, a case of a
      bilateral (18)F-FDG-avid renal oncocytoma has not been previously reported in the
      literature. A variety of malignant causes of bilateral (18)F-FDG positive renal
      masses are known, however it is important to include this benign etiology in the
      differential diagnosis. We report an unusual case of an incidental bilateral
      renal oncocytoma evaluated with contrast enhanced CT and (18)F-FDG PET/CT. 

PMID- 24900023
TI  - Lung Adenocarcinoma Staged as an Unknown Primary Presenting with Symptomatic
      Colon Metastases: Staging by 18F-FDG PET/CT.
AB  - A 66-year-old man, who presented with bright red blood per rectum, was referred
      for an (18)F-FDG PET/CT after colonoscopy showed two suspicious colon masses,
      which were biopsied to reveal an adenocarcinoma of unknown origin. PET/CT showed
      two intensely FDG-avid colon masses as well as an unsuspected FDG-avid lung mass,
      which was biopsied to reveal a primary lung adenocarcinoma. Immunohistochemistry
      confirmed the two colon metastases were of pulmonary origin. It is extremely rare
      for lung carcinoma to present with symptomatic colon metastases, with only 11
      cases described in the literature. We report the first case of the utility of
      (18)F-FDG PET/CT in staging a patient who presented with symptomatic colon
      metastases of an unknown primary lung malignancy. 

PMID- 24900024
TI  - A Case of Urethral Metastasis from Sigmoid Colon Cancer Diagnostically and
      Prognostically Indicated by F-18 FDG PET/CT.
AB  - Urethral metastasis from colorectal cancer is rare and is known to have a poor
      prognosis. A 72-year-old man with a history of colectomy and colostomy due to
      sigmoid colon cancer was admitted to the emergency room with bowel distension,
      rectal bleeding and urinary symptoms. Computed tomography of the abdominopelvis
      showed sigmoid colon cancer with multiple metastases involving the liver.
      Positron emission tomography with F-18 fluorodeoxyglucose (FDG) showed multiple
      hypermetabolic foci in the liver, penis and pubic bone, which otherwise could not
      be diagnosed. The lesions revealed no improvement with chemotherapy and
      urological surgery on follow-up F-18 FDG PET/CT. We present a case of urethral
      metastasis of sigmoid colon cancer diagnostically and prognostically indicated by
      F-18 FDG PET/CT. 

PMID- 24900025
TI  - Two Distant Muscular Metastases from Papillary Carcinoma of the Thyroid
      Demonstrated by (18)F-FDG PET/CT and Confirmed by Biopsy.

PMID- 24900026
TI  - Optical imaging for stem cell differentiation to neuronal lineage.
AB  - In regenerative medicine, the prospect of stem cell therapy holds great promise
      for the recovery of injured tissues and effective treatment of intractable
      diseases. Tracking stem cell fate provides critical information to understand and
      evaluate the success of stem cell therapy. The recent emergence of in vivo
      noninvasive molecular imaging has enabled assessment of the behavior of grafted
      stem cells in living subjects. In this review, we provide an overview of current
      optical imaging strategies based on cell- or tissue-specific reporter gene
      expression and of in vivo methods to monitor stem cell differentiation into
      neuronal lineages. These methods use optical reporters either regulated by neuron
      specific promoters or containing neuron-specific microRNA binding sites. Both
      systems revealed dramatic changes in optical reporter imaging signals in cells
      differentiating into a neuronal lineage. The detection limit of weak promoters or
      reporter genes can be greatly enhanced by adopting a yeast GAL4 amplification
      system or an engineering-enhanced luciferase reporter gene. Furthermore, we
      propose an advanced imaging system to monitor neuronal differentiation during
      neurogenesis that uses in vivo multiplexed imaging techniques capable of
      detecting several targets simultaneously. 

PMID- 24900027
TI  - Use of gamma correction pinhole bone scans in trauma.
AB  - (99m)Tc-hydroxydiphosphonate (HDP) bone scanning is a classic metabolic nuclear
      imaging method and the most frequently performed examination. Clinically, it has
      long been cherished as an indispensable diagnostic screening tool and for
      monitoring of patients with bone, joint, and soft tissue diseases. The HDP bone
      scan, the pinhole scan in particular, is known for its ability to detect
      increased, decreased, or defective tracer uptake along with magnified anatomy.
      Unfortunately, however, the findings of such uptake changes are not specific in
      many traumatic bone disorders, especially when lesions are minute and complex.
      This study discusses the recently introduced gamma correction pinhole bone scan
      (GCPBS), emphasizing its usefulness in the diagnosis of traumatic bone diseases
      including occult fractures; cervical sprains; whiplash injury; bone marrow edema;
      trabecular microfractures; evident, gaping, and stress fractures; and fish
      vertebra. Indeed, GCPBS can remarkably enhance the diagnostic feasibility of HDP
      pinhole bone scans by refining the topography, pathologic anatomy, and altered
      chemical profile of the traumatic diseases in question. The fine and precise
      depiction of anatomic and metabolic changes in these diseases has been shown to
      be unique to GCPBS, and they are not appreciated on conventional radiographs,
      multiple detector CT, or ultrasonographs. It is true that MR imaging can portray
      proton change, but understandably, it is a manifestation that is common to any
      bone disease. 

PMID- 24900028
TI  - Development of a (68)Ga-Fluorinated Porphyrin Complex as a Possible PET Imaging
      Agent.
AB  - AIM: Due to the interesting pharmacologic properties of porphyrins, the idea of
      developing a possible tumor imaging agent using PET by incorporating (68)Ga into
      a suitable porphyrin ligand was investigated. METHODS: (68)Ga-labeled 5,10,15,20
      tetrakis(pentafluoro-13 phenyl) porphyrin ((68)Ga-TFPP) was prepared using
      freshly eluted [(68)Ga]GaCl3 obtained from a 68Ge/68Ga generator developed in
      house and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (H2TFPP) for 60 min at
      100 degrees C. RESULTS: The complex was prepared with high radiochemical purity
      (>99% ITLC, >99% HPLC, specific activity: 13-14 GBq/mmol). Stability of the
      complex was checked in the final formulation and in human serum for 5 h. The
      partition coefficient was calculated for the compound (log P = 0.62). The
      biodistribution of the labeled compound in vital organs of Swiss mice bearing
      fibrosarcoma tumors was studied using scarification studies and SPECT imaging up
      to 1 h. The complex was mostly washed out from the circulation through kidneys
      and liver. The tumor-to-muscle ratio 1 h post injection was 5.13. CONCLUSION: The
      radiolabeled porphyrin complex demonstrated potential for further imaging studies
      in other tumor models.

PMID- 24900029
TI  - Effect of Animal Condition and Fluvoxamine on the Result of [(18)F]N-3
      Fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) Nortropane ([(18)F]FP-CIT)
      PET Study in Mice.
AB  - PURPOSE: PET (positron emission tomography) is a noninvasive imaging technique,
      visualizing biological aspects in vivo. In animal models, the result of PET study
      can be affected more prominently than in humans by the animal conditions or drug
      pretreatment. We assessed the effects of anesthesia, body temperature, and
      pretreatment with selective serotonin reuptake inhibitor on the results of
      [(18)F]N-3-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane
      ([(18)F]FP-CIT) PET in mice. METHODS: [(18)F]FP-CIT PET of C57BL/6 mice was
      performed in three different conditions: (1) anesthesia (isoflurane) with active
      warming (38 degrees C) as a reference; (2) no anesthesia or warming; (3)
      anesthesia without warming at room temperature. Additional groups of mice
      pretreated with escalating doses of fluvoxamine (5, 20, 40, 80 mg/kg) were imaged
      in condition (1). The time activity curve and standardized uptake value of the
      striatum, cerebral cortex, and bone were compared among these conditions.
      RESULTS: In all conditions, radioactivities of the striatum and cortex tended to
      form a plateau after rapid uptake and washout, but that of bone tended to
      increase gradually. When anesthetized without any warming, all the mice developed
      hypothermia and showed reduced bone uptake with slightly increased striatal and
      cortical uptakes compared to the reference condition. In conditions without
      anesthesia, striatal and cortical uptakes were reduced, whereas the bone uptake
      showed no change. Pretreatment with fluvoxamine increased the striatal uptake and
      striatal specific to cortical non-specific uptake ratio, whereas the bone uptake
      was reduced. CONCLUSION: Anesthesia, body temperature, and fluvoxamine affect the
      result of [(18)F]FP-CIT PET in mice by altering striatal and bone uptakes.

PMID- 24900030
TI  - The success rate of initial (131)i ablation in differentiated thyroid cancer:
      comparison between less strict and very strict low iodine diets.
AB  - PURPOSE: To decrease the risk of recurrence or metastasis in differentiated
      thyroid cancer (DTC), selected patients receive radioactive iodine ablation of
      remnant thyroid tissue or tumor. A low iodine diet can enhance uptake of
      radioactive iodine. We compared the success rates of radioactive iodine ablation
      therapy in patients who followed two different low iodine diets (LIDs). MATERIALS
      AND METHODS: The success rates of postsurgical radioactive iodine ablation in DTC
      patients receiving empiric doses of 150 mCi were retrospectively reviewed. First
      time radioactive iodine ablation therapy was done in 71 patients following less
      strict LID and 90 patients following very strict LID. Less strict LID restricted
      seafood, iodized salt, egg yolk, dairy products, processed meat, instant prepared
      meals, and multi-vitamins. Very strict LID additionally restricted rice,
      freshwater fish, spinach, and soybean products. Radioactive iodine ablation
      therapy was considered successful when follow-up (123)I whole body scan was
      negative and stimulated serum thyroglobulin level was less than 2.0 ng/mL.
      RESULTS: The success rate of patients following less strict LID was 80.3% and for
      very strict LID 75.6%. There was no statistically significant difference in the
      success rates between the two LID groups (p = 0.48). CONCLUSIONS: Very strict LID
      may not contribute to improving the success rate of initial radioactive iodine
      ablation therapy at the cost of great inconvenience to the patient.

PMID- 24900031
TI  - Retrocrural Lymph Node Metastasis Disclosed by (18)F-FDG PET/CT: A Predictor of
      Supra-diaphragmatic Spread in Ovarian Cancer.
AB  - PURPOSE: Retrocrural lymph nodes (RCLNs) communicate with retroperitoneal and
      posterior mediastinal LNs. It is possible that, when RCLNs are involved, supra
      diaphragmatic extension will occur in abdomino-pelvic cancers. The authors
      investigated performance of (18)F-FDG PET/CT to diagnose RCLN metastasis and
      whether RCLN metastases were associated with supra-diaphragmatic lymphatic
      metastases of ovarian cancer. MATERIALS AND METHODS: Sixty-seven patients with
      stage IV ovarian cancer who had undergone (18)F-FDG PET/CT were included in this
      retrospective study. Diagnostic performance of (18)F-FDG PET/CT for RCLN
      metastasis was evaluated. Patients were divided into two groups by presence or
      absence of supra-diaphragmatic LN metastasis. The prevalences of RCLN metastasis
      between the two groups were compared and the odds ratio was calculated. RESULTS:
      Sensitivity and specificity of (18)F-FDG PET/CT for RCLN metastasis were 96.3 and
      100%, respectively. Of the 67 study subjects, 27 patients had RCLN metastases
      (40.3%). Fifty patients had supra-diaphragmatic LN metastases. (18)F-FDG PET/CT
      showed 26 RCLN metastases in patients with supra-diaphragmatic LN metastases
      (54.5%), and only 1 in patients without supra-diaphragmatic LN metastasis (5.9%),
      and the difference between two groups was statistically significant (P < 0.05).
      The odds ratio that patients with RCLN metastasis would have supra-diaphragmatic
      LN metastasis was 17.3 (95% confidence interval = 2.1 to 140.9, P = 0.008).
      CONCLUSION: Performance of (18)F-FDG PET/CT to diagnose RCLN metastasis was
      excellent. RCLN metastasis revealed by (18)F-FDG PET/CT was strongly associated
      with supra-diaphragmatic LN spread of ovarian cancer. Thus, RCLN metastasis could
      be used as a predictor of supra-diaphragmatic lymphatic metastasis of ovarian
      cancer.

PMID- 24900032
TI  - Relationship Between Dual-Time Point FDG PET and Immunohistochemical Parameters
      in Preoperative Colorectal Cancer: Preliminary Study.
AB  - PURPOSE: The clinical availability of 2-deoxy-2-[18F] fluoro-D-glucose (FDG) dual
      time point positron emission tomography/computerized tomography (DTPP) has been
      investigated in diverse oncologic fields. The aim of this preliminary study was
      to evaluate the relationship between various immunohistopathologic markers
      reflecting disease progression of colorectal cancer and parameters extracted from
      FDG DTPP in colorectal cancer patients. MATERIALS AND METHODS: Forty-seven
      patients with histologically confirmed colorectal cancer were analyzed in this
      preliminary study. FDG DTPP consisted of an early scan 1 h after FDG injection
      and a delayed scan 1.5 h after the early scan. Based on an analysis of FDG DTPP,
      we estimated the maximum standardized uptake value (SUV) of tumors on the early
      and delayed scans (SUVearly and SUVdelayed, respectively). The retention index
      (RI) was calculated as follows: (SUVdelayed - SUVearly) * 100/ SUVearly. The
      clinicopathological findings (size and T and N stages) and immunohistochemical
      factors [glucose transporter 1 (GLUT-1), hexokinase 2 (HK-2), p53, P504S, and
      beta-catenin] were analyzed by visual analysis. RESULTS: The RIs calculated from
      the SUVs ranged from -1.8 to 73.4 (31.8 +/- 15.5). The RIs were significantly
      higher in patients with high T stages (T3 and T4) than with low T stages (T1 and
      T2; p < 0.05). Among the immunohistochemical analytic markers, GLUT-1 had the
      highest positive staining rate (93.6%) compared to other markers. Based on
      univariable analysis, it was shown that the RI of high-level GLUT-1 expression
      was significantly higher than low-level GLUT-1 expression (p = 0.01), and the RI
      of high-level p53 expression was slightly higher than low-level p53 expression (p
      = 0.08). Multivariate analysis to investigate a link between RI and
      clinicopathologic parameters of colorectal carcinoma showed that GLUT-1, p53, and
      T staging were independently connected with increased RIs (p < 0.05, total) using
      backward selection methods. There was no significant statistical relationship
      between SUVearly and SUVdelayed and clinicopathologic parameters in this study.
      CONCLUSION: The RIs obtained from preoperative colorectal cancers had a
      significant relationship to tumor size, T staging, GLUT-1, and p53, in contrast
      to SUVearly or SUVdelayed. Compared with previous reports, our results showed
      that RI can better predict GLUT-1 expression than HK-2 and other
      immunohistochemical markers. This study demonstrated that the RI might have the
      potential to be applied as a prognostic marker in preoperative colorectal cancer.

PMID- 24900033
TI  - The Feasibility of (18)F-Fluorothymidine PET for Prediction of Tumor Response
      after Induction Chemotherapy Followed by Chemoradiotherapy with S-1/Oxaliplatin
      in Patients with Resectable Esophageal Cancer.
AB  - PURPOSE: The aim of this study was to determine whether (18)F-fluorothymidine
      (FLT) PET is feasible for the early prediction of tumor response to induction
      chemotherapy followed by concurrent chemoradiotherapy in patients with esophageal
      cancer. METHODS: This study was prospectively performed as a collateral study of
      "randomized phase II study of preoperative concurrent chemoradiotherapy with or
      without induction chemotherapy with S-1/oxaliplatin in patients with resectable
      esophageal cancer". (18)F-FLT positron emission tomography (PET) images were
      obtained before and after two cycles of induction chemotherapy, and the percent
      change of maximum standardized uptake value (SUVmax) was calculated. All patients
      underwent esophagography, gastrofiberoscopy, endoscopic ultrasonography (EUS),
      computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) PET at baseline and 3
      4 weeks after completion of concurrent chemoradiotherapy. Final tumor response
      was determined by both clinical and pathologic tumor responses after surgery.
      RESULTS: The 13 patients for induction chemotherapy group were enrolled until
      interim analysis. In a primary tumor visual analysis, the tumor detection rates
      of baseline (18)F-FLT and (18)F-FDG PET were 85% and 100%, respectively. The
      tumor uptakes on (18)F-FLT PET were lower than those of (18)F-FDG PET. Among nine
      patients who completed second (18)F-FLT PET, eight patients were responders and
      one patient was a non-responder in the assessment of final tumor response. The
      percent change of SUVmax in responders ranged from 41.2% to 79.2% (median 57.1%),
      whereas it was 10.2% in one non-responder. CONCLUSION: The percent change of
      tumor uptake in (18)F-FLT PET after induction chemotherapy might be feasible for
      early prediction of tumor response after induction chemotherapy and concurrent
      chemoradiotherapy in patients with esophageal cancer.

PMID- 24900034
TI  - Compression of the right pulmonary artery by a massive descending aortic aneurysm
      causing bilateral perfusion defects on pulmonary scintigraphy.
AB  - A 67-year-old woman, who presented with a 2 month history of dyspnea, had a
      ventilation and perfusion lung scan that showed absent perfusion of the entire
      right lung with normal ventilation, as well as a rounded matched defect in the
      left lower lung adjacent to midline, suspicious for an aortic aneurysm or
      dissection. CT pulmonary angiography revealed a massive descending aortic
      aneurysm compressing the right pulmonary artery as well as the left lung
      parenchyma, accounting for the bilateral perfusion scan defects. We present the
      Xe-133 ventilation, Tc-99m MAA perfusion and CT pulmonary angiography imaging
      findings of this rare case. 

PMID- 24900035
TI  - Monitoring Therapeutic Response in a Case of Extrapulmonary Tuberculosis by
      Serial F-18 FDG PET/CT.
AB  - Due to the low yield of AFB smear and culture in extrapulmonary tuberculosis,
      therapeutic responses of patients with extrapulmonary tuberculosis are usually
      monitored clinically and/or radiographically. Such monitoring techniques,
      however, are not enough to provide effective diagnosis if a remnant lesion exists
      after treatment. Tuberculosis presents hypermetabolic activity on F-18
      fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG
      PET/CT) scanning. Reported herein is a case of extrapulmonary tuberculosis where
      the therapeutic response was assessed via serial F-18 FDG PET/CT scanning, which
      was useful for detecting the extent of extrapulmonary tuberculosis and for
      estimating the patient's therapeutic response. 

PMID- 24900036
TI  - Orbital Metastases as Presenting Sign of Lung Carcinoma: Detection of Primary
      Malignancy and Disease Burden by F-18 FDG PET/CT.
AB  - Metastases to orbit occur rarely but are the most common form of malignant
      orbital tumors. Usually the orbital metastases occur in disseminated disease.
      Very rarely orbital metastases can be the presenting feature of systemic
      malignancy. We report here a case with orbital metastases as the presenting
      feature of lung malignancy and describe the utility of FDG PET/CT as one-stop
      shop imaging modality in this setting. 

PMID- 24900037
TI  - Prosthesis-Related Abscess on In-111 Leukocyte SPECT/CT Imaging.

PMID- 24900038
TI  - Solitary Cerebellar Metastasis of Cecal Cancer, Visualized Using F-18 FDG PET/CT.

PMID- 24900039
TI  - High-dose (111)in induces g1 cell cycle arrest and cell death in rat bone marrow
      mesenchymal stem cells.
AB  - PURPOSE: This study was performed to evaluate the effect of (111)In-labeling on
      the cell growth, cycle and viability of bone marrow mesenchymal stem cells
      (BMSCs). METHODS: Rat BMSCs were labeled with various doses of (111)In (0.4-11.1
      Bq/cell). The growth curve of (111)In-BMSCs was obtained up to 14th day of
      labeling. The cell cycle was evaluated by 5-bromo-2-deoxyuridine (BrdU) labeling
      or propidium iodide (PI) staining. Senescent cells were counted under a light
      microscope after staining with 5-bromo-4-chloro-3-indolyl-D-galactopyranoside.
      Flow cytometry was performed to measure apoptotic and necrotic fractions after
      staining with annexin V-FITC and PI. RESULTS: The growth of BMSCs labeled with
      higher doses of (111)In (4.4 or 11.1 Bq/cell) was significantly inhibited from
      the 3rd day of labeling. Flow cytometry revealed less BrdU-positive BMSCs at 11.1
      Bq (111)In/cell during all measurement days and G1 arrest at 4.4 and 11.1 Bq
      (111)In/cell. Significant increases in apoptosis and necrosis were also observed
      at 4.4 (3.04%/1.35%) and 11.1 Bq (111)In/cell (9.07%/3.18%) on the 14th day
      (control = 1.60%/0.39%). However, no cellular senescence was visualized up to the
      14th day. CONCLUSION: A high dose of (111)In-labeling induced cell cycle arrest
      and death in BMSCs; therefore, it should be used with a careful dosimetry in case
      of applying it to humans.

PMID- 24900040
TI  - Comparison of the Influence on the Liver Function Between Thyroid Hormone
      Withdrawal and rh-TSH Before High-Dose Radioiodine Therapy in Patients with Well
      Differentiated Thyroid Cancer.
AB  - PURPOSE: An elevated thyroid stimulating hormone level (TSH) is essential to
      stimulate the uptake of radioiodine into thyroid remnants and metastases of
      thyroid cancer when a patient undergoes high-dose radioiodine therapy. Nowadays,
      recombinant human thyroid stimulating hormone (rh-TSH) is increasingly used
      instead of the classic method of thyroid hormone withdrawal (THW). However,
      beyond the therapeutic effects, clinical differences between the two methods have
      not yet been clearly demonstrated. The aim of this work was to investigate the
      effects of the two methods, especially on liver function. METHODS: We identified
      143 evaluable patients who were further divided into two groups: THW and rh-TSH.
      We first reviewed the aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) levels, which were measured during the admission period
      for total thyroidectomy. We called these liver enzyme levels "base AST" and "base
      ALT." We also assessed other chemistry profiles, including AST, ALT, total
      cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB),
      and triglyceride (TG), which were measured on admission day for high-dose
      radioiodine therapy. We called these liver enzyme levels "follow-up AST" and
      "follow-up ALT." We compared the changes in base and follow-up liver enzyme
      levels and the other chemistry profiles between the two groups. RESULTS: The base
      AST and base ALT levels of the two groups were within normal range, and there was
      no significant difference between the two groups. In contrast to these base liver
      enzyme levels, follow-up liver enzyme levels between the two groups showed
      significant differences. Patients in the THW group had higher follow-up AST and
      ALT levels than did the rh-TSH group. Patients in the THW group also had higher
      levels of total cholesterol and LDL cholesterol than did the patients in the rh
      TSH group. However there were no statistically significant differences in ALP,
      total bilirubin, and triglyceride levels between the two groups. CONCLUSIONS: In
      this retrospective analysis of liver function, the use of rh-TSH for high-dose
      radioiodine therapy had less of an effect on liver function and cholesterol
      levels than dose thyroid hormone withdrawal. This suggests that rh-TSH can be
      used effectively and safely especially for patients with metabolic syndrome.

PMID- 24900041
TI  - Diagnostic Criteria on (18)F-FDG PET/CT for Differentiating Benign from Malignant
      Focal Hypermetabolic Lesions of Parotid Gland.
AB  - PURPOSE: We investigated PET/CT diagnostic criteria for differentiating benign
      from malignant parotid lesions with focal (18)F-FDG uptake. METHODS: The subjects
      of the study were 272 patients who exhibited focal (18)F-FDG uptake of the
      parotid gland. Sixty-eight pathologically confirmed parotid lesions from 67
      patients were included. The maximum SUV (SUVmax), uptake patterns (homogeneous
      vs. heterogeneous), size measured by CT, maximum Hounsfield units (HUmax) and
      margins on CT (well vs. ill defined) of each parotid lesion on PET/CT images were
      compared with final diagnoses. RESULTS: Thirty-two parotid lesions were
      histologically proven to be malignant. There were significant differences in
      uptake patterns (cancer incidence, heterogeneous:homogeneous = 79.2%:29.5%, p <
      0.0001) and margins on CT (cancer incidence, ill:well defined = 84.4%:13.3%, p <
      0.0001) between benign and malignant lesions. The cancer risks of parotid lesions
      were 89.5% with heterogeneous uptake and ill-defined margins, 70.6% with
      heterogeneous uptake or ill-defined margins (no overlap in subjects) and 9.3%
      with homogeneous uptake and well-defined margins (p < 0.0001). When any lesion
      with heterogeneous uptake or ill-defined margins was regarded as malignant, the
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy were 90.6% (29/32), 80.6% (29/36), 80.6% (29/36), 90.6% (29/32) and
      85.6% (58/68), respectively. For predicting malignancy, combined PET/CT criteria
      showed better sensitivity, NPV and accuracy than PET-only criteria, and had a
      tendency to have more accurate results than CT-only criteria. There were no
      significant differences in SUVmax, size or HUmax between benign and malignant
      lesions. CONCLUSION: Uptake patterns and margins on CT are useful PET/CT
      diagnostic criteria for differentiating benign from malignant lesions.

PMID- 24900042
TI  - Usefulness of F-18 FDG PET/CT in the Evaluation of Early Treatment Response After
      Interventional Therapy for Hepatocellular Carcinoma.
AB  - PURPOSE: This retrospective study investigated the usefulness of F-18
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) after interventional therapy for hepatocellular carcinoma (HCC).
      METHODS: Between March 2007 and November 2010, 31 patients (24 men, 7 women; mean
      age, 61.8 +/- 11.0 years) with 45 lesions underwent PET/CT within 1 month after
      interventional therapy for HCC. Twenty-six patients with 40 lesions underwent
      transcatheter arterial chemoembolization (TACE), two patients with 2 lesions
      underwent radiofrequency ablation (RFA), and three patients with 3 lesions
      underwent percutaneous ethanol injection therapy (PEIT). Patients with a history
      of previous interventional therapy were excluded. Visual analysis was graded as
      positive when FDG was observed as an eccentric, nodular, or infiltrative pattern,
      and negative in case of isometabolic, hypometabolic, or rim-shaped uptake. For
      quantitative analysis, the standardized uptake value (SUV) was measured by region
      of interest technique. Maximum SUV (SUVmax) was assessed, and the ratio of SUVmax
      of tumor to mean SUV of normal liver (TNR) was calculated. The patients were
      divided into two groups, with and without residual tumor, based on 6-month
      clinical follow-up with serum alpha-fetoprotein and contrast-enhanced abdominal
      CT. RESULTS: Of the 45 lesions, 24 were classified in the residual tumor group
      and the other 21 lesions in the no residual tumor group. No residual tumor was
      detected after RFA or PEIT. By visual analysis, the respective values for
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy were 87.5, 71.4, 77.8, 83.3, and 80.0 %. However, there were no
      significant differences in the SUVmax and TNR between the two groups.
      CONCLUSIONS: It is suggested that FDG PET/CT may play a role in the evaluation of
      early treatment response after interventional therapy for HCC. The results
      indicate that FDG PET/CT visual analysis may be more useful than quantitative
      analysis. Further prospective studies with a large number of patients and
      established protocol are needed to substantiate our results.

PMID- 24900043
TI  - A Case of Enterocutaneous Fistula Diagnosed with Tc-99m DTPA Fistulography Using
      Hybrid SPECT/CT.
AB  - Enterocutaneous fistula (ECF) is a communication between the bowel lumen and the
      skin, which especially occurs post-operatively and is associated with significant
      morbidity and mortality. Correct diagnosis and anatomical information of ECF are
      crucial for a patient's management. Here, we present a case of ECF clearly
      diagnosed by hybrid single-photon emission computed tomography/computed
      tomography (SPECT/CT). A 61-year-old man was admitted to our hospital with
      persistent pus discharge from a surgical wound of previous cystectomy and ileal
      conduit formation. Initially, he was assessed with fistulography, and ECF was
      suspected by intraluminal contrast media. As clinical symptom and signs were not
      definitely matched with ECF, Tc-99m diethylene triamine pentaacetic acid (DTPA)
      SPECT/CT was performed for the evaluation of fistular tract as an alternative
      method. On the SPECT/CT after injection of Tc-99m DTPA to the putative fistular
      opening, fistular as well as intraluminal radioactivity was clearly visualized.
      SPECT/CT is a sensitive and safe diagnostic imaging tool for ECF. 

PMID- 24900044
TI  - Classical imaging triad in a very young child with swyer-james syndrome.
AB  - Swyer-James syndrome (SJS) or Swyer-James-MacLeod syndrome is a rare disorder
      characterized by roentgenographical hyperlucency of one lung, lobe, or part of a
      lobe. As originally described, it shows a unilateral small lung with hyperlucency
      and air trapping on radiographs. It is postinfectious obliterative bronchiolitis
      due to childhood respiratory infection. In SJS, the involved lung or portion of
      the lung does not grow normally. The characteristic radiologic appearance is that
      of pulmonary hyperlucency on chest X-ray/CT caused by over-distention of the
      alveoli in conjunction with diminished arterial flow detected on Tc-99 m MAA
      pulmonary perfusion scan. Radionuclide pulmonary ventilation studies are
      considered difficult to perform in very young children as patient co-operation is
      crucial to achieve adequate tracer entry into the lungs. We present here the case
      of a female child aged 2 years, who presented with chronic productive cough and
      fever off and on for 1.5 years. She had classical features on imaging and
      markedly diminished ventilation on Tc-99 m DTPA aerosol study. Our case
      highlights the typical findings on ventilation-perfusion scan (V/Q scan) and
      suggests that it is possible to conduct a satisfactory ventilation study with Tc
      99 m DTPA aerosol even in very young children. 

PMID- 24900045
TI  - Myeloid Sarcoma and Acute Myelomonocytic Leukemia in an Adolescent with Tetrasomy
      8: Staging with (18)F-FDG PET/CT.
AB  - Tetrasomy 8 is a relatively rare chromosomal abnormality that has been reported
      in only 33 cases in hematologic disorders. It is known for its association with
      aggressive acute myeloid leukemia (AML) and myeloid sarcoma and is considered a
      very poor prognostic factor. Myeloid sarcoma is a rare hematologic malignancy
      characterized by tumor masses consisting of immature myeloid cells, presenting at
      an extramedullary site. We present a case of a 17-year-old boy referred for an
      (18)F-FDG PET/CT for the evaluation of pleural masses and spinal bone lesions
      seen on CT, after presenting with a 4 month history of chest pain. The PET/CT
      revealed extensive FDG-avid extramedullary disease in the soft tissues of the
      chest, abdomen, and pelvis, which were biopsy-proven to be myeloid sarcoma, as
      well as extensive intramedullary disease biopsy proven to be AML. This is the
      first report of the use of (18)F-FDG PET/CT to stage a subset of aggressive AML
      and myeloid sarcoma in a patient with an associated chromosomal abnormality
      (tetrasomy 8). 

PMID- 24900046
TI  - A Case of Acute Q Fever Hepatitis Diagnosed by F-18 FDG PET/CT.
AB  - A 53-year-old man with fever of unknown origin underwent F-18 fluorodeoxyglucose
      positron emission tomography/computed tomography (F-18 FDG PET/CT) as a workup
      for a fever of unknown origin. On presentation, he complained of fever, chills,
      and myalgia. The F-18 FDG PET/CT scan showed diffusely increased uptake of the
      liver with mild hepatomegaly. A liver biopsy then revealed fibrin-ring granulomas
      typically seen in Q fever. The patient was later serologically diagnosed as
      having acute Q fever as the titers for C. burnetii IgM and IgG were 64:1 and
      16:1, respectively. He recovered completely following administration of
      doxycycline. This indicates that F-18 FDG PET/CT may be helpful for identifying
      hepatic involvement in Q fever as a cause of fever of unknown origin. 

PMID- 24900047
TI  - Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease.
AB  - Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer
      syndrome with a variety of benign and malignant tumors such as retinal and
      central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts
      and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal
      cystadenomas. Cross-sectional modalities (computed tomography and magnetic
      resonance imaging) as well as ultrasound play a major role in the initial
      evaluation and follow-up of the various manifestations of VHL disease. Ga-68
      labeled somatostatin receptor analogs already have a significant role in the
      diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural
      crest tumors. Herein, we report a case presenting a variety of malignancies in
      VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one
      stop-shop imaging modality in the management of VHL disease. 

PMID- 24900048
TI  - Giant Cell Tumor Pulmonary Metastases Mimic Primary Malignant Pulmonary Nodules
      on (18)F-FDG PET/CT.
AB  - A 59-year-old man with a 30-year history of multiple recurrences of a giant cell
      tumor (GCT) of the left knee was referred for an (18)F-FDG PET/CT to evaluate a
      solitary pulmonary nodule. The nodule was mildly FDG-avid, raising suspicion of
      malignancy. It was excised and histologically proven to be a GCT pulmonary
      metastasis. A follow-up PET/CT done 2 years later revealed a new, larger lung
      mass that was more intensely FDG-avid, but of the same histology. This rare
      report highlights a pitfall in the evaluation of solitary pulmonary lesions by
      (18)F-FDG PET/CT in patients with GCT of the bone. 

PMID- 24900049
TI  - A Patient with Psoriatic Arthritis Imaged with FDG-PET/CT Demonstrated an Unusual
      Imaging Pattern with Muscle and Fascia Involvement: A Case Report.
AB  - We describe the case of a patient with known history of psoriasis that presented
      with 1 year of unexplained fever, muscle weakness and marked weight loss,
      suspicious for B symptoms of a malignant origin. [(18)F]-Fluorodeoxyglucose
      positron emission tomography-computed tomography (FDG-PET/CT) scans demonstrated
      an unusual serpiginous pattern of uptake in the fascia and muscles as well as
      lymph node activity. Multiple histological samples, including a final PET-probe
      guided lymph node surgical resection, excluded malignancy and confirmed the
      diagnosis of reactive inflammatory changes, with a plausible diagnosis of
      autoimmune lymphoproliferative syndrome with associated lymphadenitis, fasciitis
      and myositis, possibly mediated by tumor necrosis factor (TNF) inhibitor. To our
      knowledge, there is no evidence of a previously reported FDG uptake pattern of
      fascia and muscle involvement in psoriatic arthritis. 

PMID- 24900050
TI  - Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of (99m)Tc-MDP.

PMID- 24900051
TI  - Metastatic Breast Lesion to the Falx Detected with PET-CT.

PMID- 24900052
TI  - F-18 FDG PET/CT in Bilateral Diffuse Pulmonary Lymphangitic Carcinomatosis.

PMID- 24900053
TI  - Heme products post-radiofrequency ablation obscure tumor recurrence on MR but not
      on PET-CT.

PMID- 24900054
TI  - Imaging Myocardial Ischemia and Reperfusion Injury via Cy5.5-Annexin V.
AB  - AIM: The aim of this article is to present the results of an imaging study of
      myocardial apoptosis induced by ischemia/reperfusion injury. METHODS: Twenty nude
      mice were randomly divided into an experimental group (10 mice) and control group
      (10 mice). In the experimental group, myocardial apoptosis was induced by
      ligation of the left anterior descending coronary artery (LAD) for 30 min. This
      was followed by reperfusion for 90 min. In the control group, the heart was
      exposed for the same length of time as in the experimental group. Cy5.5-annexin V
      (25 MUg) was injected into both sets of mice after the onset of reperfusion. At
      90 min post-injection, the mice were imaged. The region of interest (ROI) was
      obtained, and the fluorescence intensity of the ROI was quantified. The animals
      were sacrificed, and myocardial apoptosis was assayed by TUNEL assay. RESULTS:
      Fluorescence intensity in the ischemia/reperfusion hearts was significantly
      higher than that in the control group (P < 0.05). In the TUNEL assay, more
      apoptotic cells were observed in the experimental group than in the control
      group, correlating with imaging results. CONCLUSION: Fluorescence imaging of
      Cy5.5-annexin V in a mouse model of myocardial ischemia/reperfusion can be used
      in vivo as a noninvasive means of detecting ischemia/reperfusion-induced
      apoptotic cells in the heart.

PMID- 24900055
TI  - Implications of three-phase bone scintigraphy for the diagnosis of bisphosphonate
      related osteonecrosis of the jaw.
AB  - PURPOSE: Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is a well
      known serious complication of BP treatment. This study was undertaken to evaluate
      the diagnostic usefulness of three-phase bone scintigraphy in patients with
      BRONJ. METHODS: Forty-one patients (48 lesions) with clinically proven BRONJ (2
      males, 39 females, age 74.3 +/- 6.7 years) underwent Tc-99 m HDP bone
      scintigraphy. Visual interpretation and semiquantitative analysis of uptakes
      using lesion-to-contralateral uptake ratios during the blood pool phase (BUR) and
      during the osseous phase (OUR) were performed, and relations were sought between
      these and various clinical parameters. RESULTS: Three-phase bone scintigraphy
      showed increased perfusion and blood pooling in 21 (63.6 %) and 27 (81.8 %) of 33
      lesions, respectively. The osseous phase was positive for 45 (93.8 %) of the 48
      lesions. Of the four inflammatory clinical parameters of BRONJ [pus discharge,
      pain, swelling, and erythrocyte sedimentation rate (ESR)], patients with three or
      more parameters had more positive findings in vascular and blood pool phase
      images (p = 0.033, p = 0.027). By semiquantitative analysis, patients with a
      positive ESR had statistically higher BUR and OUR (both p < 0.001). Higher stage
      BRONJ lesions had higher OUR than lower stage lesions (p = 0.003). In addition,
      bone scintigraphy revealed three clinically covert BRONJ lesions without bone
      exposure, and four patients were up-staged based on bone scintigraphy.
      CONCLUSIONS: Bone scintigraphy provides a relatively sensitive means of detecting
      BRONJ, so it was helpful for accurate BRONJ staging. Furthermore, increased
      uptakes in vascular and blood pool phases of three-phase bone scintigraphy were
      related to the inflammatory activity of BRONJ.

PMID- 24900056
TI  - Correlation between (18)f-fluorodeoxyglucose uptake and epidermal growth factor
      receptor mutations in advanced lung cancer.
AB  - PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) gene have been
      identified as potential targets for the treatment and prognostic factors for non
      small cell lung cancer (NSCLC). We assessed the correlation between
      fluorodeoxyglucose (FDG) uptake and EGFR mutations, as well as their prognostic
      implications. METHODS: A total of 163 patients with pathologically confirmed
      NSCLC were enrolled (99 males and 64 females; median age, 60 years). All patients
      underwent FDG positron emission tomography before treatment, and genetic studies
      of EGFR mutations were performed. The maximum standardized uptake value (SUVmax)
      of the primary lung cancer was measured and normalized with regard to liver
      uptake. The SUVmax between the wild-type and EGFR mutant groups was compared.
      Survival was evaluated according to SUVmax and EGFR mutation status. RESULTS:
      EGFR mutations were found in 57 patients (60.8 %). The SUVmax tended to be higher
      in wild-type than mutant tumors, but was not significantly different (11.1 +/-
      5.7 vs. 9.8 +/- 4.4, P = 0.103). The SUVmax was significantly lower in patients
      with an exon 19 mutation than in those with either an exon 21 mutation or wild
      type (P = 0.003 and 0.009, respectively). The EGFR mutation showed prolonged
      overall survival (OS) compared to wild-type tumors (P = 0.004). There was no
      significant difference in survival according to SUVmax. Both OS and progression
      free survival of patients with a mutation in exon 19 were significant longer than
      in patients with wild-type tumors. CONCLUSION: In patients with NSCLC, a mutation
      in exon 19 was associated with a lower SUVmax and is a reliable predictor for
      good survival.

PMID- 24900057
TI  - Hepatic FDG Uptake is not Associated with Hepatic Steatosis but with Visceral Fat
      Volume in Cancer Screening.
AB  - PURPOSE: We aimed to evaluate the relation between visceral fat volume and
      fluorodeoxyglucose (FDG) uptake of the liver measured by maximum or mean
      standardized uptake value. METHODS: We retrospectively analyzed 96 consecutive
      records of positron emission tomography/computed tomography (PET/CT) performed
      for cancer screening between May 2011 and December 2011. Subjects were divided
      into 2 groups according to Hounsfield unit (HU) of the liver comparing with that
      of the spleen. The control group (20 women, 56 men) demonstrating HU of the liver
      equal or greater than that of the spleen included 76 patients, while the fatty
      liver group (2 women, 18 men) showing HU of the liver less than that of the
      spleen included 20 patients. We compared FDG uptake of the liver and visceral fat
      volume between two groups. We evaluated correlation of hepatic FDG uptake
      measured by maximum or mean standardized uptake value (SUV) with visceral fat
      volume and attenuation. RESULTS: The fatty liver disease group showed higher
      aspartate aminotransferase (AST)of (24.42 +/- 7.22, p = 0.012), alanine
      aminotransferase (ALT) of (25.16 +/- 11.68, p = 0.001), body mass index (BMI) of
      (24.58 +/- 3.29, p = 0.021), and visceral fat volume (3063.53 +/- 1561.43, p =
      0.011) than the control group. There were no statistically significant
      differences of mean standardized uptake value of the liver (liver SUVmean) (2.73
      +/- 0.19, p = 0.723), maximum standardized uptake value of the liver (liver
      SUVmax) (3.39 +/- 0.53, p = 0.8248) and liver SUVmean/spleen SUVmean (1.13 +/-
      0.10, p = 0.081) between the two groups. Strong correlations were shown between
      liver SUVmean and BMI (r = 0.609, p < 0.001) and between liver SUVmean and
      visceral fat volume (r = 0.457, p < 0.001). Liver SUVmax was also strongly
      correlated with BMI (r = 0.622, p = 0.001) and visceral fat volume (r = 0.547, p
      < 0.001). There was no significant association of mean attenuation value of the
      liver (liver HUmean) with liver SUVmean (r = -0.003, p = 0.979) or liver SUVmax
      (r = -0.120, p = 0.244). CONCLUSION: Hepatic FDG uptake quantified as SUVmean or
      SUVmax is not correlated with hepatic steatosis but with visceral fat volume in
      cancer screening.

PMID- 24900058
TI  - Comparison of SUVs Normalized by Lean Body Mass Determined by CT with Those
      Normalized by Lean Body Mass Estimated by Predictive Equations in Normal Tissues.
AB  - PURPOSE: Standardized uptake values (SUVs) normalized by lean body mass (LBM)
      determined by CT were compared with those normalized by LBM estimated using
      predictive equations (PEs) in normal liver, spleen, and aorta using (18)F-FDG
      PET/CT. METHODS: Fluorine-18 fluorodeoxyglucose (F-FDG) positron emission
      tomography/computed tomography (PET/CT) was conducted on 453 patients. LBM
      determined by CT was defined in 3 ways (LBMCT1-3). Five PEs were used for
      comparison (LBMPE1-5). Tissue SUV normalized by LBM (SUL) was calculated using
      LBM from each method (SULCT1-3, SULPE1-5). Agreement between methods was assessed
      by Bland-Altman analysis. Percentage difference and percentage error were also
      calculated. RESULTS: For all liver SULCTs vs. liver SULPEs except liver SULPE3,
      the range of biases, SDs of percentage difference and percentage errors were 
      0.17-0.24 SUL, 6.15-10.17 %, and 25.07- 38.91 %, respectively. For liver SULCTs
      vs. liver SULPE3, the corresponding figures were 0.47-0.69 SUL, 10.90-11.25 %,
      and 50.85-51.55 %, respectively, showing the largest percentage errors and
      positive biases. Irrespective of magnitudes of the biases, large percentage
      errors of 25.07-51.55 % were observed between liver SULCT1-3 and liver SULPE1-5.
      The results of spleen and aorta SULCTs and SULPEs comparison were almost
      identical to those for liver. CONCLUSION: The present study demonstrated
      substantial errors in individual SULPEs compared with SULCTs as a reference
      value. Normalization of SUV by LBM determined by CT rather than PEs may be a
      useful approach to reduce errors in individual SULPEs.

PMID- 24900059
TI  - Value of Surveillance (18)F-FDG PET/CT in Colorectal Cancer: Comparison with
      Conventional Imaging Studies.
AB  - PURPOSE: To assess the value of PET/CT for detecting local or distant recurrence
      in patients who undergo surgery for colorectal cancer (CRC) and to compare the
      accuracy of PET/CT to that of conventional imaging studies (CIS). METHODS: Tumor
      surveillance PET/CT scans done between March 2005 and December 2009 of disease
      free patients after surgery with or without adjuvant chemotherapy for CRC were
      retrospectively studied. CIS (serial enhanced CT from lung base to pelvis and
      plain chest radiograph) were performed within 1 month of PET/CT. We excluded
      patients with distant metastasis on initial staging, a known recurrent tumor, and
      a lack of follow-up imaging. The final diagnosis was based on at least 6 months
      of follow-up with colonoscopy, biopsy, and serial imaging studies in combination
      with carcinoembryonic antigen levels. RESULTS: A total of 262 PET/CT scans of 245
      patients were included. Local and distant recurrences were detected in 27 cases
      (10.3%). On case-based analysis, the overall sensitivity, specificity, and
      accuracy were 100, 97.0, and 97.3% for PET/CT and 85.1, 97.0, and 95.8% for CIS,
      respectively. On lesion-based analysis, PET/CT detected more lesions compared to
      CIS in local recurrence and lung metastasis. PET/CT and CIS detected the same
      number of lesions in abdominal lymph nodes, hepatic metastasis, and peritoneal
      carcinomatosis. PET/CT detected two more metachronous tumors than did CIS in the
      lung and thyroid gland. CONCLUSION: PET/CT detected more recurrences in patients
      who underwent surgery for CRC than did CIS and had the additional advantage of
      evaluating the entire body during a single scan.

PMID- 24900060
TI  - Dual-time-point FDG PET/CT: Is It Useful for Lymph Node Staging in Patients with
      Non-Small-Cell Lung Cancer?
AB  - PURPOSE: Dual-time-point (DTP) FDG PET/CT has been shown to be useful for lymph
      node (LN) staging in patients with non-small-cell lung cancer (NSCLC). The aim of
      this study was to evaluate the LN staging ability of DTP FDG PET/CT in the
      predominant area of pulmonary tuberculosis. METHODS: Sixty-nine NSCLC patients
      underwent DTP PET/CT. Regions of interest were placed on each LN of each station,
      and the maximum SUVs were measured. Three variables were obtained: (1) the SUV on
      the early scan (SUVearly), (2) the SUV on the delayed scan (SUVdelayed), and (3)
      the retention index of the SUV (RI). Each patient had one final LN stage and
      three other LN stages according to the cutoff values of SUVearly, SUVdelayed, and
      RI. RESULTS: In the LN-based analysis, the area under the ROC curve of SUVdelayed
      (0.884) was significantly larger (P < 0.01) than those of SUVearly (0.868) and RI
      (0.717). Among the three variables, SUVdelayed was more accurate (P < 0.01) for
      detecting the mediastinal LN metastasis than SUVearly and RI. In the patient
      based analysis, SUVdelayed had correctly determined LN stages in 55 of 69
      patients (sensitivity, specificity, and accuracy = 88.7 %, 50.0 %, and 79.7 %),
      whereas SUVearly and RI correctly determined LN stages in 53 and 52 patients,
      respectively. CONCLUSIONS: In this study, comparing the diagnostic efficacy of
      SUVearly, SUVdelayed, and RI for LN staging in patients with NSCLC, SUVdelayed
      was the most accurate variable for LN staging. DTP PET/CT could provide improved
      diagnostic accuracy for the LN staging of NSCLC.

PMID- 24900061
TI  - Prognostic Significance of Volume-based Metabolic Parameters by (18)F-FDG PET/CT
      in Gallbladder Carcinoma.
AB  - PURPOSE: We investigated the prognostic values of volume-based metabolic
      parameters by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography
      (PET)/computed tomography (CT) in gallbladder carcinoma patients and compared
      them with other prognostic parameters. MATERIALS AND METHODS: We enrolled 44
      patients, who were initially diagnosed with gallbladder carcinoma and undergoing
      (18)F-FDG PET/CT. Various metabolic volume-based PET parameters of primary
      tumors, including maximum and average standardized uptake values (SUVmax,
      SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were
      measured in gallbladder carcinoma patients using mediastinal blood pool activity
      as a threshold SUV for determining the tumor boundaries. Overall survival
      analysis was performed using the Kaplan-Meier method with PET parameters and
      other clinical variables. For determining independent prognostic factors, Cox
      proportional hazards regression analysis was performed. RESULTS: Of the 44
      enrolled patients, cancer- or treatment-related death occurred in 30 (68.2 %).
      The mean clinical follow-up period was 22.2 +/- 10.4 m (range, 0.6-35.9 m).
      Univariate analysis demonstrated that clinical or pathologic TNM stage (P <
      0.001), treatment modality (P < 0.001), MTV (cutoff = 135 cm(3), P = 0.001), and
      TLG (cutoff = 7,090, P < 0.05) were significant prognostic factors. In
      multivariate analysis, both clinical or pathologic TNM stage [hazard ratio (HR) =
      2.019 (I vs II), 21.287 (I vs III), and 24.354 (I vs IV); P = 0.001) and TLG (HR
      = 2.930; P < 0.05) were independent prognostic factors for predicting overall
      survival. CONCLUSIONS: In gallbladder cancer, TLG of the primary tumor, a volume
      based metabolic parameter, is a significant independent prognostic factor for
      overall survival in conjunction with the clinical or pathological TNM stage.

PMID- 24900062
TI  - Prognostic value of SUVmax measured by Fluorine-18 Fluorodeoxyglucose Positron
      Emission Tomography with Computed Tomography in Patients with Pancreatic Cancer.
AB  - PURPOSE: Recent studies have been conducted on the relationship between
      fluorodeoxyglucose (FDG) uptake in F-18 FDG PET/CT and prognosis in patients with
      pancreatic cancer, but these studies have been carried out in small numbers of
      patients. The aim of this retrospective study was to determine in a large number
      of patients whether glucose metabolism as assessed by F-18 FDG PET/CT provides
      prognostic information independent of established prognostic factors in patients
      with pancreatic cancer. METHODS: We reviewed retrospectively the medical records
      of 165 patients (men 105, women 60, mean age 67 +/- 10 years) with a diagnosis of
      pancreatic cancer that had undergone F-18 FDG PET/CT as part of a pretreatment
      workup from January 2004 to December 2009. Subsequently, all patients underwent
      surgery, cyberknife, radiotherapy, and/or chemotherapy. For the analysis,
      patients were classified by age, demographic data, maximum standardized uptake
      value (SUVmax), size, location, serum level of CA19-9, type of treatment, and
      AJCC stage. The relationship between FDG uptake and survival was analyzed using
      the Kaplan-Meier with log-Rank test and Cox's proportional-hazard regression
      methods. RESULTS: Median survival for all 165 study subjects was 290 days and
      median SUV by PET/CT was 5.8 (range: 0-25.1). Patients were allocated to high (>
      4.1) and low (<=4.1) SUV groups, and median survivals of these patients were 229
      days and 610 days, respectively, which were significantly different (p < 0.0001).
      Furthermore, SUVmax was found to be significantly related to survival in each
      stage, i.e., there were 1267 days in stage I, 440 days in stage II, 299 days in
      stage III, and 143 days in stage IV (p < 0.0001). The median survival was also
      found to be significantly related to tumor size (p = 0.001), site (p = 0.0298),
      serum level of CA19-9 (p = 0.0017), distant metastasis (p < 0.0001), and type of
      treatment (p < 0.0001). Multivariate analysis study revealed that the patients
      with a low SUV (p = 0.0298), a lower serum level of CA19-9 (p = 0.0071), a lower
      stage (p = 0.0017), and no distant metastasis (p < 0.0001) had longer survivals.
      In addition, SUVmax values were found to have a similar hazard ratio of distant
      metastasis; it was well known predictor. Furthermore, SUVmax values showed a
      higher hazard ratio than that of other clinicopathologic predictors. CONCLUSION:
      The present study shows that SUVmax on F-18 FDG PET/CT can provide a prognostic
      information in patients with pancreatic cancer.

PMID- 24900063
TI  - Application of rhenium-186 radiosynovectomy in elbow diffuse pigmented
      villonodular synovitis. - a case report with multiple joint involvement.
AB  - After surgical therapy of diffuse pigmented villonodular synovitis (DPVNS),
      recurrence is seen in almost half of the patients. The effectiveness of
      radiosynovectomy (RSV) in preventing recurrence and complaints of DPVNS is well
      known. Elbow involvement in DPVNS is a very rare condition; therefore, RSV in
      elbow hasn't been experienced widely. The aim of this case report is to show the
      effectiveness of RSV with rhenium-186 (Re-186) sulfide colloid. We applied Re-186
      sulfide colloid to the elbow joint of DPVNS patients six weeks after arthroscopic
      synovectomy. As a result, the patient did not have any complaints, and our
      findings are compatible with residue or recurrence on magnetic resonance imaging
      (MRI) in sixth and twentieth month controls after administration. We concluded
      that Re-186 is an effective adjuvant therapy for the prevention of recurrence and
      complaints. 

PMID- 24900064
TI  - Hibernoma: Intense Uptake on F18-FDG PET/CT.
AB  - Hibernoma is a rare benign but metabolically active tumor of brown fat origin,
      that can have cross-sectional imaging characteristics similar to those of other
      fat-containing tumors, such as lipomas and liposarcomas, and its presence can
      lead to false-positive interpretation by exhibiting increased F18
      fluorodeoxyglucose (F18-FDG) activity. A 46-year-old woman was diagnosed with
      dermatofibrosarcoma protuberans underwent F18-FDG positron emission
      tomography/computed tomography (PET/CT) for detecting recurrence after excision.
      F18-FDG PET/CT showed incidental intense uptake in the back in addition to
      increased F18-FDG uptake at the previous lesion site. To our knowledge, this is
      the first case report of intense F18-FDG uptake in hibernoma in Korea. 

PMID- 24900065
TI  - Growing Cardiac Hemangioma on Serial F-18 FDG PET/CT.
AB  - Cardiac hemangiomas are extremely rare, benign tumors, which can occur anywhere
      in the heart. Symptoms are variable according to the size, extension and tumor
      location, but most cases are asymptomatic and are detected incidentally. They may
      grow, remain stable and regress; therefore, the natural course of the tumors is
      unpredictable. Diagnosis mainly depends upon echocardiography, CT, MRI and
      angiography. Reports of detection by F-18 FDG PET/CT are very limited. We report
      a case of cardiac hemangioma attached to the right ventricle, compressing the
      ventricle. It was revealed incidentally on F-18 FDG PET/CT for routine evaluation
      of thyroid cancer. During two serial F-18 FDG PET/CTs, it grew from 2.8 cm to 4.0
      cm with mild FDG uptake. After surgery, the patient remained stable without any
      complications. 

PMID- 24900066
TI  - H-type Tracheoesophageal Fistula Detected by Radionuclide Salivagram.

PMID- 24900067
TI  - Endometrial Cancer with Cervical Extension Mimicking Dual Concordant Endometrial
      and Cervical Malignancy by F-18 FDG PET and MRI.

PMID- 24900068
TI  - Malignant Phyllodes Tumor of the Breast Metastasizing to the Vulva: (18)F-FDG PET
      CT Demonstrating Rare Metastasis from a Rare Tumor.

PMID- 24900069
TI  - Rituximab-Induced Lung Injury in a Case of NHL: Diagnosis and Follow-Up on FDG
      PET/CT.

PMID- 24900070
TI  - The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide
      Symporter Expressing Cells.
AB  - PURPOSE: The heat shock protein 90 inhibitor, tanespimycin, is an anticancer
      agent known to increase iodine accumulation in normal and cancerous thyroid
      cells. Iodine accumulation is regulated by membrane proteins such as sodium
      iodide symporter (NIS) and pendrin (PDS), and thus we attempted to characterize
      the effects of tanespimycin on those genes. METHODS: Cells were incubated with
      tanespimycin in order to evaluate (125)I accumulation and efflux ability.
      Radioiodine uptake and efflux were measured by a gamma counter and normalized by
      protein amount. RT-PCR were performed to measure the level of gene expression.
      RESULTS: After tanespimycin treatment, (125)I uptake was increased by ~2.5-fold
      in FRTL-5, hNIS-ARO, and hNIS-MDA-MB-231 cells, but no changes were detected in
      the hNIS-HeLa cells. Tanespimycin significantly reduced the radioiodine efflux
      rate only in the FRTL-5 cells. In the FRTL-5 and hNIS-ARO cells, PDS mRNA levels
      were markedly reduced; the only other observed alteration in the levels of NIS
      mRNA after tanespimycin treatment was an observed increase in the hNIS-ARO cells.
      CONCLUSIONS: These results indicate that cellular responses against tanespimycin
      treatment differed between the normal rat thyroid cells and human cancer cells,
      and the reduction in the (125)I efflux rate by tanespimycin in the normal rat
      thyroid cells might be attributable to reduced PDS gene expression.

PMID- 24900071
TI  - The Clinical Usefulness of (99m)Tc HMPAO Leukocyte/(99m)Tc Phytate Bone Marrow
      Scintigraphy for Diagnosis of Prosthetic Knee Infection: A Preliminary Study.
AB  - PURPOSE: The preferred radionuclide imaging procedure for diagnosing prosthetic
      joint infection is combined radiolabeled leukocyte/(99m)Tc sulfur colloid bone
      marrow scintigraphy, which has an accuracy of over 90 %. Unfortunately, sulfur
      colloid is no longer available in South Korea. In this study, we evaluated the
      usefulness of (99m)Tc phytate, a substitute for (99m)Tc sulfur colloid, when
      combined with radiolabeled leukocyte scintigraphy in suspected prosthetic knee
      infections. METHODS: Eleven patients (nine women, two men; mean age 72 +/- 6
      years) with painful knee prostheses and a suspicion of infection underwent both
      (99m)Tc HMPAO leukocyte scintigraphy (LS) and (99m)Tc phytate bone marrow
      scintigraphy (BMS). The combined images were interpreted as positive for
      infection when radioactivity in the LS at the site of clinical interest clearly
      exceeded that of the BMS (discordant); they were interpreted as negative when the
      increased activity in the LS was consistent with an increased activity in the BMS
      (concordant). The final diagnosis was made with microbiological or intraoperative
      findings and a clinical follow-up of at least 12 months. RESULTS: Five of eleven
      patients were diagnosed as having an infected prosthesis. The overall
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and diagnostic accuracy of the combined LS/BMS were 100 %, 83 %, 83
      %, 100 % and 91 %, respectively. CONCLUSION: We find that combined (99m)Tc HMPAO
      LS/(99m)Tc phytate BMS shows comparable diagnostic performance to other studies
      utilizing sulfur colloid. Combined (99m)Tc HMPAO LS/(99m)Tc phytate BMS is
      therefore expected to be an acceptable alternative to combined radiolabeled
      LS/(99m)Tc sulfur colloid BMS for diagnosing prosthetic knee infections.

PMID- 24900072
TI  - Validation of Simple Quantification Methods for (18)F-FP-CIT PET Using Automatic
      Delineation of Volumes of Interest Based on Statistical Probabilistic Anatomical
      Mapping and Isocontour Margin Setting.
AB  - PURPOSE: (18)F-FP-CIT positron emission tomography (PET) is an effective imaging
      for dopamine transporters. In usual clinical practice, (18)F-FP-CIT PET is
      analyzed visually or quantified using manual delineation of a volume of interest
      (VOI) for the striatum. In this study, we suggested and validated two simple
      quantitative methods based on automatic VOI delineation using statistical
      probabilistic anatomical mapping (SPAM) and isocontour margin setting. METHODS:
      Seventy-five (18)F-FP-CIT PET images acquired in routine clinical practice were
      used for this study. A study-specific image template was made and the subject
      images were normalized to the template. Afterwards, uptakes in the striatal
      regions and cerebellum were quantified using probabilistic VOI based on SPAM. A
      quantitative parameter, QSPAM, was calculated to simulate binding potential.
      Additionally, the functional volume of each striatal region and its uptake were
      measured in automatically delineated VOI using isocontour margin setting. Uptake
      volume product (QUVP) was calculated for each striatal region. QSPAM and QUVP
      were compared with visual grading and the influence of cerebral atrophy on the
      measurements was tested. RESULTS: Image analyses were successful in all the
      cases. Both the QSPAM and QUVP were significantly different according to visual
      grading (P < 0.001). The agreements of QUVP or QSPAM with visual grading were
      slight to fair for the caudate nucleus (kappa = 0.421 and 0.291, respectively)
      and good to perfect to the putamen (kappa = 0.663 and 0.607, respectively). Also,
      QSPAM and QUVP had a significant correlation with each other (P < 0.001).
      Cerebral atrophy made a significant difference in QSPAM and QUVP of the caudate
      nuclei regions with decreased (18)F-FP-CIT uptake. CONCLUSION: Simple
      quantitative measurements of QSPAM and QUVP showed acceptable agreement with
      visual grading. Although QSPAM in some group may be influenced by cerebral
      atrophy, these simple methods are expected to be effective in the quantitative
      analysis of (18)F-FP-CIT PET in usual clinical practice.

PMID- 24900073
TI  - Detectability of T-Measurable Diseases in Advanced Gastric Cancer on FDG PET-CT.
AB  - PURPOSE: Usefulness of FDG PET-CT in monitoring response in locally advanced
      gastric cancer has been reported. The purpose of this study was to evaluate the
      related factors to detect measurable diseases in advanced gastric cancer on FDG
      PET-CT. METHODS: We retrospectively reviewed 38 patients diagnosed as having
      advanced gastric cancer. We defined the measurable diseases when there was
      visualized tumor of which maximum standardized uptake value (SUVmax) was higher
      than 1.35*SUVmax of liver + 2*SD of liver SUV. We evaluated what kinds of factors
      from the clinicopathologic features were related to identifying measurable
      diseases. RESULTS: Of 38 patients with advanced gastric cancer, 18 (50 %) had
      measurable tumors on FDG PET-CT. Measurable tumors were significantly more
      frequent in well or moderately differentiated adenocarcinoma (70.5 % vs 35.3 %, p
      < 0.05), in the tumors located at antrum or angle (66.7 % vs 29.4 %, p < 0.05)
      and in the elderly group (age of 55 years old or more, 72.0 % vs 8.3 %, p <
      0.001) than the others, respectively. By multivariate analysis, age at diagnosis
      was the only independent predictor for the measurable disease on FDG PET-CT.
      CONCLUSION: We found that age at diagnosis, as well as histologic types and
      location of tumors, were the affecting factors to detect measurable disease on
      FDG PET-CT in patients with advanced gastric cancer. Our study suggests that
      elderly patients of age of 55 years old or more can frequently have T-measurable
      disease on FDG PET-CT in advanced gastric cancer and FDG PET-CT will be helpful
      to monitor measurable disease.

PMID- 24900074
TI  - Usefulness of (18)F-FDG PET/CT for the Evaluation of Bone Marrow Involvement in
      Patients with High-Grade Non-Hodgkin's Lymphoma.
AB  - PURPOSE: To assess the usefulness of (18)F-fluorodeoxyglucose PET/CT in the
      detection of bone marrow (BM) involvement of high-grade non-Hodgkin's lymphoma
      (NHL). METHODS: One hundred twenty patients with newly diagnosed diffuse large B
      cell lymphoma or peripheral T-cell lymphoma between January 2007 and June 2011,
      who received BM trephine biopsy and (18)F-FDG PET/CT before chemotherapy, were
      included in this retrospective study. We reviewed their (18)F-FDG PET/CT images
      and bone marrow biopsy (BMB) results. After reviewing the images, we reviewed the
      medical records and radiological findings of interesting patients. RESULTS: There
      were 23 (18)F-FDG PET/CT scans in which the marrow was considered to be abnormal
      (either positive or equivocal), and 97 (18)F-FDG PET/CT scans were regarded as
      having negative FDG uptake. Of 120 patients, 100 (83.3 %) had a concordant result
      of BM interpretation between (18)F-FDG PET/CT and BMB, and the remaining 20
      patients had discordant results. Among 23 patients with either positive or
      equivocal (18)F-FDG PET/CT scans, 1 of 12 patients with 'positive' (18)F-FDG
      PET/CT had a lymphomatous involvement on BMB. In contrast, 10 of 11 patients with
      'equivocal' BM hypermetabolism were reported as having positive involvement by
      BMB. Patients with abnormal (18)F-FDG PET/CT had significantly higher mSUVhighest
      than those with normal FDG-PET/CT. CONCLUSIONS: (18)F-FDG PET/CT and BMB are
      complementary techniques in assessing the presence of BM involvement in patients
      with high-grade NHL. The increasing availability of (18)F-FDG PET/CT will raise
      the need for additional biopsy for FDG-avid lesions, especially in patients with
      negative standard BMBs. (18)F-FDG PET/CT can be useful as a decision-making tool
      for determining whether to perform a standard BMB or targeted biopsy to the FDG
      avid lesion as an initial staging procedure. A direct bone biopsy for FDGpositive
      bone lesions should be included in staging guidelines in future. In (18)F-FDG
      PET/CT-negative cases, BMB is still a powerful procedure, but BMB alone is
      insufficient for full evaluation of BM.

PMID- 24900075
TI  - Prognostic Significance of Metabolic Tumor Volume Measured by (18)F-FDG PET/CT in
      Operable Primary Breast Cancer.
AB  - PURPOSE: We investigated whether PET indices measured by (18) F
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) can predict prognosis in patients with operable primary breast cancer.
      METHODS: We reviewed 53 patients with operable primary breast cancer who
      underwent pretreatment FDG PET/CT. PET indices, maximum standardized uptake value
      (SUV) and metabolic tumor volume (MTV), were measured in the primary breast tumor
      (P), metastatic lymph nodes (N) and total tumor (T). The Cox proportional hazards
      model was used with age, tumor size, clinical lymph node status, method of
      surgery, presence or absence of neoadjuvant chemotherapy, histological type,
      histological grade, hormone receptors and HER2 status to predict disease-free
      survival (DFS) and overall survival (OS). RESULTS: Median follow-up period was 50
      months (range, 17-73 months), during which 17 patients had recurrent disease and
      nine of whom died. The univariate analysis showed that high SUV of N (NSUV, P =
      0.011), MTV of N (NMTV, P = 0.011) and MTV of T (TMTV, P = 0.045) as well as high
      histological grade (P = 0.008), negative estrogen (P = 0.045) and negative
      progesterone (P = 0.029) receptor status were associated with shorter DFS. High
      NSUV (P = 0.035), NMTV (P = 0.035) and TMTV (P = 0.035) as well as high
      histological grade (P = 0.012) and negative estrogen receptor status (P = 0.009)
      were associated with shorter OS. NSUV, NMTV and TMTV were found to be
      significantly associated with high histological grade (P = 0.005). However, those
      failed to be statistically significant prognostic factors on multivariate
      analysis. CONCLUSIONS: PET indices seem to be useful in the preoperative
      evaluation of prognosis in patients with operable primary breast cancer. NSUV,
      NMTV and TMTV might be considerable factors associated with patient outcome in
      operable breast cancer.

PMID- 24900076
TI  - Metabolic Tumor Volume Measured by F-18 FDG PET/CT can Further Stratify the
      Prognosis of Patients with Stage IV Non-Small Cell Lung Cancer.
AB  - PURPOSE: This study aimed to further stratify prognostic factors in patients with
      stage IV non-small cell lung cancer (NSCLC) by measuring their metabolic tumor
      volume (MTV) using F-18 fluorodeoxyglucose (FDG) positron emission
      tomography/computed tomography (PET/CT). MATERIALS AND METHODS: The subjects of
      this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion
      glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on
      F-18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in
      torso. Optimal cutoff values of PET parameters were measured by receiver
      operating characteristic (ROC) curve analysis. Kaplan-Meier survival curves were
      used for evaluation of progression-free survival (PFS). The univariate and
      multivariate Cox proportional hazards models were used to select the significant
      prognostic factors. RESULTS: Univariate analysis showed that both MTV and TLG of
      primary lung lesion (MTV-lung and TLG-lung) were significant factors for
      prediction of PFS (P < 0.001, P = 0.038, respectively). Patients showing lower
      values of MTV-lung and TLG-lung than the cutoff values had significantly longer
      mean PFS than those with higher values. Hazard ratios (95 % confidence interval)
      of MTV-lung and TLG-lung measured by univariate analysis were 6.4 (2.5-16.3) and
      2.4 (1.0-5.5), respectively. Multivariate analysis revealed that MTV-lung was the
      only significant factor for prediction of prognosis. Hazard ratio was 13.5 (1.6
      111.1, P = 0.016). CONCLUSION: Patients with stage IV NSCLC could be further
      stratified into subgroups of significantly better and worse prognosis by MTV of
      primary lung lesion.

PMID- 24900077
TI  - Optimal CT Number Range for Adipose Tissue When Determining Lean Body Mass in
      Whole-Body F-18 FDG PET/CT Studies.
AB  - PURPOSE: The aim of this study was to define an optimal CT number range
      applicable to adipose tissue (AT) measurement in modern PET/CT systems. METHODS:
      CT number (in Hounsfield units, HU) was measured in three different pure AT
      compartments in 53 patients. CT number range for AT was determined in three
      different ways, including pixel histogram analysis, to take the effect of partial
      volume averaging into account. The effect of changing the CT number range for AT
      on the total AT volume was investigated. RESULTS: The lower limits for CT number
      for pure subcutaneous AT, retroperitoneal AT, and visceral AT were -140, -140,
      and -130 HU, respectively. The corresponding upper limits were -70, -71, and -52
      HU. The CT number range for AT using three methods when considering partial
      volume averaging was -144 to -141 HU to -30 to -33 HU, showing similar values
      between the three methods. The optimal CT number range for AT based on these data
      was -140 to -30 HU. Increases in total AT volume of 7.5 % and 1.8 % were found
      when the upper or lower limit was extended using 10 HU intervals, respectively,
      compared with the reference range of -140 to -30 HU. CONCLUSION: This study
      demonstrated that the optimal CT number range of AT that is applicable to modern
      PET/CT systems can be defined as -140 to -30 HU. The use of this CT number range
      of AT allowed lean body mass to be determined in whole-body F-18 FDG PET/CT
      studies.

PMID- 24900078
TI  - Dual thyroid ectopia with graves' disease: a case report and a review of the
      literature.
AB  - Ectopic thyroid or thyroid ectopia is a rare developmental anomaly with the
      prevalence of 1 per 100,000-300,000 population. Even rarer, such an anomaly
      manifests as dual thyroid ectopia. To our best knowledge, only one case has been
      reported on dual thyroid ectopia with Graves' disease in the English literature.
      We present here a case of dual thyroid ectopia complicated by Graves' disease,
      whereby the diagnosis was rendered through judicious use of various diagnostic
      modalities coupled with a close clinical follow-up. In this case, therapeutic
      consideration should be personalized with proper informed consent of the patient.

PMID- 24900079
TI  - Primary Malignant Fibrous Histiocytoma in Mediastinum: Imaging with (18)F-FDG
      PET/CT.
AB  - Malignant fibrous histiocytoma (MFH) is the most common soft tissue tumor which
      often occurs in the extremities and the retroperitoneum. Primary mediastinal MFH
      is rare; thus, findings on (18)F-fluorodeoxyglucose positron emission
      tomography/computed tomography ((18)F-FDG PET/CT) of mediastinal MFH have not
      been reported yet. We report herein the case of a 64-year-old man who was
      presented with a superior mediastinal mass. The mass showed intense (18)F-FDG
      uptake with central metabolic defect on PET/CT. The maximum standardized uptake
      value was 17.4. After tumor removal via median sternotomy, an MFH of the
      storiform-pleomorphic type was diagnosed on histopathologic examination. We
      present the first report of (18)F-FDG PET/CT imaging of MFH in the superior
      mediastinum. 

PMID- 24900080
TI  - Incidental Finding of Appendiceal Adenocarcinoma in F-18 FDG PET/CT for Health
      Screening.
AB  - F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) that simultaneously offers anatomic and metabolic information is widely
      used and has become an effective modality in many clinical fields, especially
      oncology, and also may detect an unexpected primary cancer. Appendiceal carcinoma
      is relatively uncommon and not associated with characteristic symptoms. We report
      the case of a 53-year-old man with appendiceal adenocarcinoma, who had only mild
      fever. The tumor was detected early on F-18 FDG PET/CT for health screening. 

PMID- 24900081
TI  - Coexistence of physiologic and abnormal muscle uptake of fluorine-18
      fluorodeoxyglucose in a patient with plasma cell leukemia.

PMID- 24900082
TI  - Detection of Penile Metastasis from Bladder Cancer Using F-18 FDG PET/CT.

PMID- 24900083
TI  - Peripheral Tuberculous Lymphadenitis Masquerading as Metastatic Gastric Carcinoma
      on F-18 FDG Dual Time Point PET/CT.

PMID- 24900084
TI  - Fibrous Dysplasia Mimicking Bone Metastasis on Both Bone Scintigraphy and (18)F
      FDG PET-CT: Diagnostic Dilemma in a Patient with Breast Cancer.

PMID- 24900085
TI  - Incidental Finding of a Left-over Guide-Wire on a Positron Emission Tomography.

PMID- 24900086
TI  - Feasibility of PET Template-Based Analysis on F-18 FP-CIT PET in Patients with De
      Novo Parkinson's Disease.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of FP-CIT PET
      template-based quantitative analysis on F-18 FP-CIT PET in patients with de novo
      Parkinson's disease (PD), compared with MR-based and manual methods. We also
      assessed the correlation of quantitative parameters of those methods with
      clinical severity of the disease. METHODS: Forty patients with de novo PD
      underwent both MRI and F-18 FP-CIT PET. Images were spatially normalized to a
      standardized PET template. Mean counts of 4 ROIs: putamen, caudate, occipital
      cortex and cerebellum, were obtained using the quantification program, Korean
      Statistical Probabilistic Anatomical Map (KSPAM). Putamen-to-caudate ratio (PCR),
      asymmetry index (ASI), specific-to-nonspecific ratios with two different
      references: to occipital cortex (SOR) and cerebellum (SCR) were compared.
      Parameters were also calculated from manually drawn ROI method and MR
      coregistrated method. RESULTS: All quantitative parameters showed significant
      correlations across the three different methods, especially between the PET-based
      and manual methods. Among them, PET-based SOR and SCR values showed an excellent
      correlation and concordance with those of manual method. In relationship with
      clinical severity, only ASI achieved significantly inverse correlations with H&Y
      stage and UPDRS motor score. There was no significant difference between the
      quantitative parameters of both occipital cortex and cerebellum in all three
      methods, which implied that quantitation using PET-based method could be
      reproducible regardless of the reference region. CONCLUSIONS: Quantitative
      parameters using FP-CIT PET template-based method correlated well with those
      using laborious manual method with excellent concordance. Moreover, PET-based
      quantitation was less influenced by the reference region than MR-based method. It
      suggests that PET-based method can provide objective and quantitative parameters
      quickly and easily as a feasible analysis in place of conventional method.

PMID- 24900087
TI  - Differential Diagnosis of Borderline Ovarian Tumors from Stage I Malignant
      Ovarian Tumors using FDG PET/CT.
AB  - PURPOSE: Borderline ovarian tumors (BOTs) are more common in young women of
      reproductive age, and exhibit a better prognosis than malignant ovarian tumors
      (MOTs). Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) were compared in their ability to differentiate BOTs from stage I MOTs.
      METHODS: Among 173 patients who had preoperative FDG PET/CT due to ovarian
      neoplasms between November 2006 and March 2009, there were 13 patients with BOTs
      or stage I MOTs. For differential diagnosis of the two tumors, cancer antigen-125
      (CA-125) level, the longest diameter of tumors, metabolic indices including
      maximum standardized uptake value (SUVmax), and volumetric indices including
      metabolic tumor volume (MTV) were compared, respectively. RESULTS: The BOT group
      (n = 7) was comprised of five mucinous and two serous tumors, and the MOT group
      (n = 6) was comprised of three endometrioid, two clear cell and one mucinous
      tumors. Among the comparisons between two groups, SUVmax of the BOT group was
      significantly lower than that of the MOT group (2.9 +/- 1.5 vs. 6.6 +/- 2.9, p =
      0.0223); otherwise, no significant difference was found in age, CA-125, diameter,
      or MTV. By receiver-operating characteristic curve analysis, SUVmax of 3.7 was
      the best cutoff value to differentiate BOTs from stage I MOTs, with a sensitivity
      of 83.3 % and specificity of 85.7, and the area under curve of 0.893 (p = 0.0001,
      95 % CI: 0.601~0.993). CONCLUSIONS: We demonstrated that SUVmax could distinguish
      BOTs from stage I MOTs, with a high sensitivity and specificity. Metabolic
      indices determined by FDG PET/CT were more suitable than volumetric indices for
      differential diagnosis of the two tumors.

PMID- 24900088
TI  - Evaluation of (18)F-FDG Uptake Pattern in Brown Adipose Tissue Over Extended Time
      Period as Assessed by Multiple Time Point (18)F-FDG-PET.
AB  - PURPOSE: To study the (18)F-FDG uptake pattern in brown adipose tissue (BAT) over
      an extended time period, by multiple-time-point fluorodeoxyglucose positron
      emission tomography (FDG-PET) imaging. The primary objective for this kind of
      research was that it could form a basis and may have further implications for
      obesity research, metabolic diseases and for cachexia of both malignant and
      benign origin. METHODS: A total of 12 patients who had undergone routine FDG-PET
      for disease evaluation and had demonstrated prominent BAT uptake in their
      baseline scans were selected. The patients with the diagnosis of neuroendocrine
      tumors were excluded. Maximum standardized uptake values (SUVmax) were calculated
      in the BAT of the supraclavicular and paravertebral areas of either side, and
      were analyzed separately to examine their behavior individually. Time activity
      curves (TACs) were generated for [A] BAT SUVmax values and [B] SUVmax ratio of
      BAT/lung (B/L SUVmax ratio) at various time points. RESULTS: Ten out of the 12
      patients were imaged at four time points, and two patients were imaged for two
      time points. Amongst a total of n = 30 sites, 23 were imaged at four time points
      and seven were imaged at two time points. Seventeen out of 30 area sites (56.67
      %) demonstrated a peak value at 60 min and a falling trend of SUVmax afterwards;
      the remaining showed a peak uptake value between 85 and 300 min after the first
      scan (i.e. 145-360 min after injection), and falling values thereafter. With
      regard to the B/L SUVmax ratio, ten out of 30 sites (33.33 %) demonstrated peak
      uptake at 60 min, and the remaining showed a rise, with peak uptake at times
      between 85 and 300 min after the first scan (i.e. 145-360 min after injection)
      and falling values thereafter. No additional area of BAT uptake was observed over
      the extended time period in this study. CONCLUSION: Wide variability was observed
      in the BAT FDG uptake over an extended period of time. Nearly half of the sites
      demonstrated an increase in FDG uptake until 360 min (i.e. 6 h) after injection,
      while the remaining half showed peak uptake at 1 h and subsequent fall of uptake.
      In the future, it will be worthwhile to study whether there exists any difference
      in time course of FDG uptake in brown fat between patients with cancer and those
      scanned for benign etiologies, or between obese and non-obese individuals.

PMID- 24900089
TI  - Direct Determination of Lean Body Mass by CT in F-18 FDG PET/CT Studies:
      Comparison with Estimates Using Predictive Equations.
AB  - PURPOSE: The purpose of this study was to estimate lean body mass (LBM) using CT
      (LBM CTs) and compare the results with LBM estimates of four different predictive
      equations (LBM PEs) to assess whether LBM CTs and LBM PEs can be used
      interchangeably for SUV normalization. METHODS: Whole-body F-18 FDG PET/CT
      studies were conducted on 392 patients. LBM CT1 is modified adipose tissue-free
      body mass, and LBM CT2 is adipose tissue-free body mass. Four different PEs were
      used for comparison (LBM PE1-4). Agreement between the two measurement methods
      was assessed by Bland-Altman analysis. We calculated the difference between two
      methods (bias), the percentage of difference, and the limits of agreement,
      expressed as a percentage. RESULTS: For LBM CTs vs. LBM PEs, except LBM PE3, the
      ranges of biases and limits of agreement were -3.77 to 3.81 kg and 26.60-35.05 %,
      respectively, indicating the wide limits of agreement and differing magnitudes of
      bias. For LBM CTs vs. LBM PE3, LBM PE3 had wider limits of agreement and greater
      positive bias (44.28-46.19 % and 10.49 to 14.04 kg, respectively), showing
      unacceptably large discrepancies between LBM CTs and LBM PE3. CONCLUSION: This
      study demonstrated that there are substantial discrepancies between individual
      LBM CTs and LBM PEs, and this should be taken into account when LBM CTs and LBM
      PEs are used interchangeably between patients.

PMID- 24900090
TI  - Is it Feasible to Use the Commercially Available Autoquantitation Software for
      the Evaluation of Myocardial Viability on Small-Animal Cardiac F-18 FDG PET Scan?
AB  - PURPOSE: To evaluate the reliability of quantitation of myocardial viability on
      cardiac F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans
      with three different methods of visual scoring system, autoquantitation using
      commercially available autoquantitation software, and infarct-size measurement
      using histogram-based maximum pixel threshold identification on polar-map in rat
      hearts. METHODS: A myocardial infarct (MI) model was made by left anterior
      descending artery (LAD) ligation in rat hearts. Eighteen MI rats underwent
      cardiac FDG-PET-computed tomography (CT) twice within a 4-week interval.
      Myocardium was partitioned into 20 segments for the comparison, and then we
      quantitated non-viable myocardium on cardiac FDG PET-CT with three different
      methods: method A-infarct-size measurement using histogram-based maximum pixel
      threshold identification on polar-map; method B-summed MI score (SMS) by a four
      point visual scoring system; method C-metabolic non-viable values by commercially
      available autoquantitation software. Changes of non-viable myocardium on serial
      PET-CT scans with three different methods were calculated by the change of each
      parameter. Correlation and reproducibility were evaluated between the different
      methods. RESULTS: Infarct-size measurement, visual SMS, and non-viable values by
      autoquantitation software presented proportional relationship to each other. All
      the parameters of methods A, B, and C showed relatively good correlation between
      each other. Among them, infarct-size measurement (method A) and autoquantitation
      software (method C) showed the best correlation (r = 0.87, p < 0.001). When we
      evaluated the changes of non-viable myocardium on the serial FDG-PET-CT- however,
      autoquantitation program showed less correlation with the other methods. Visual
      assessment (method B) and those of infarct size (method A) showed the best
      correlation (r = 0.54, p = 0.02) for the assessment of interval changes.
      CONCLUSIONS: Commercially available quantitation software could be applied to
      measure the myocardial viability on small animal cardiac FDG-PET-CT scan. This
      kind of quantitation showed good correlation with infarct size measurement by
      histogram-based maximum pixel threshold identification. However, this method
      showed the weak correlation when applied in the measuring the changes of non
      viable myocardium on the serial scans, which means that the caution will be
      needed to evaluate the changes on the serial monitoring.

PMID- 24900091
TI  - (99m)Tc-Labeled RBC Scan in a Patient with Blue Rubber Bleb Nevus Syndrome: A
      Case Report.
AB  - Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by
      cutaneous and gastrointestinal vascular malformations. We report here the case of
      a 13-year-old patient with BRBNS who was suffering from chronic anemia. His chief
      complaint was melena. Contrast-enhanced abdominal computed tomography showed
      multiple hemangiomas in the small bowel. (99m)Tc-labeled red blood cell (RBC)
      scan identified the bleeding sites in the small bowel. The patient underwent
      exploratory laparotomy with segmental resection and multiple wedge resection of
      the small bowel. The pathological results confirmed the multiple cavernous
      hemangiomas. This case confirms the critical role of the (99m)Tc-labeled RBC scan
      in localizing the bleeding sites in patients with BRBNS. 

PMID- 24900092
TI  - Brain SPECT Analysis After Constraint-Induced Movement Therapy in Young Children
      with Hemiplegic Cerebral Palsy: Case Report.
AB  - Constraint-induced movement therapy (CIMT) was shown recently to be promising for
      improving upper-limb function in children with cerebral palsy (CP). This study
      investigated the changes in cerebral perfusion with single-photon emission
      computerized tomography (SPECT) after modified CIMT (child-friendly CIMT) in
      young hemiplegic girls. Two young children with left hemiplegic CP were studied
      with SPECT at rest before and after the CIMT period, and they also performed
      standardized upper motor function tests [Jebsen hand function test, quality of
      upper extremity skills test (QUEST), and dynamic electromyography (EMG)]. The
      cerebral perfusion SPECT revealed regional perfusion increase in the motor cortex
      area in the affected hemisphere, and the changes associated with functional gain.
      Our cases showed that intensive movement therapy appears to change local cerebral
      perfusion and SPECT could show these changes in children with hemiplegic CP. 

PMID- 24900093
TI  - Extensive Extranodal Involvement of Rare Sites in Non Hodgkin's Lymphoma Detected
      on (18)F- FDG PET-CT: A Case Report.
AB  - We present a case of a 23 year-old male treated for Hodgkin's lymphoma who
      developed diffuse large B-cell lymphoma (DLBCL) 8 years after achieving
      remission. (18)F-fluorodeoxyglucose positron emission tomography computed
      tomography ((18)F-FDG PET-CT) was done, which revealed extensive extranodal
      involvement of bilateral atria, bilateral kidneys, ileo-caecal junction and left
      testis along with mesenteric and retroperitoneal lymph nodal involvement. Renal
      and cardiac lesions were not detected by contrast-enhanced CT. Simultaneous
      lymphomatous involvement of rare sites such as heart, kidneys and testis in a
      single patient has not been reported before. 

PMID- 24900094
TI  - Breast Sparganosis Incidentally Detected by FDG PET/CT.
AB  - Sparganosis is a rare, parasitic infection that is caused by the plercercoid
      tapeworm larvae of the genus Spirometra. Sparganosis is transmitted by ingestion
      of larvae-containing water or intermediate hosts, such as raw amphibians, and
      usually presented with a subcutaneous nodule in the abdominal wall, extremities,
      and genital organs. Among the various involved organs, the breast is a seldom
      encountered site for sparganosis. However, breast sparganosis has clinical
      importance, since it is generally presented with an indolent palpable mass that
      mimics malignancy, even without evidence of inflammation. Herein, we report a
      case of breast sparganosis that was detected incidentally by FDG PET/CT during
      staging work ups in a patient with gall bladder cancer. 

PMID- 24900095
TI  - Uterine Epithelioid Angiosarcoma on F-18 FDG PET/CT.
AB  - Uterine epithelioid angiosarcoma can have conventional imaging characteristics
      similar to those of other uterine tumors, such as leiomyoma, leiomyosarcomas or
      hemangioendothelioma. Uterine epithelioid angiosarcoma exhibiting increased
      fluorine-18 fluorodeoxyglucose (F-18 FDG) activity can be misdiagnosed. A 61-year
      old woman who was diagnosed with uterine epithelioid angiosarcoma underwent F-18
      FDG positron emission tomography/computed tomography (PET/CT) as a part of the
      pretreatment work up for surgery. F-18 FDG PET/CT showed an intense F-18 FDG
      uptake in the uterus in addition to increased F-18 FDG uptake at the paraaortic
      and aortocaval lymph nodes. To our knowledge, this is the first case report of
      intense F-18 FDG uptake in uterine epithelioid angiosarcoma in Korea. 

PMID- 24900096
TI  - Benign Schwannoma Mimicking Metastatic Lesion on F-18 FDG PET/CT in
      Differentiated Thyroid Cancer.
AB  - We report a case of benign schwannoma mimicking metastatic carcinoma. A 55-year
      old female with papillary thyroid carcinoma underwent total thyroidectomy. F-18
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT)
      demonstrated a focal hypermetabolic lesion with maximum standardized uptake value
      (SUVmax) 5.3 at the right chest wall. Conventional chest CT demonstrated a 5.4 cm
      ovoid mass lesion between the intercostal muscles and liver. Pathology revealed a
      schwannoma by tumor excision. This case demonstrates that benign schwannoma may
      demonstrate FDG uptake mimicking metastatic carcinoma. 

PMID- 24900097
TI  - Diagnosis of Bronchobiliary Fistula-Utility of 99 m Tc-Mebrofenin Scan and
      SPECT/CT.

PMID- 24900098
TI  - A Papillary Thyroid Tumor Detected by (18)F-FDG-PET/CT in a Pediatric Patient
      with Cowden Syndrome.

PMID- 24900099
TI  - (18)F-FDG PET/CT Presentation in a Patient Diagnosed with Large Cell
      Neuroendocrine Carcinoma of Uncertain Primary.

PMID- 24900100
TI  - A Rare Case of Malignant Granular Cell Tumor of the Colon Incidentally Detected
      by (18) F-FDG Positron Emission Tomography/Computed Tomography.

PMID- 24900101
TI  - Prognostic Value of Normal Perfusion but Impaired Left Ventricular Function in
      the Diabetic Heart on Quantitative Gated Myocardial Perfusion SPECT.
AB  - PURPOSE: This study aimed at identifying the predictive parameters on
      quantitative gated myocardial perfusion single-photon emission computed
      tomography (QG-SPECT) in diabetic patients with normal perfusion but impaired
      function. METHODS: Among the 533 consecutive diabetic patients, 379 patients with
      normal perfusion on rest Tl-201/dipyridamole-stress Tc-99m sestamibi Gated SPECT
      were enrolled. Patients were grouped into those with normal post-stress left
      ventricular function (Group I) and those with impaired function (EF <50 or
      impaired regional wall motion, Group II). We investigated cardiac events and
      cause of death by chart review and telephone interview. Survival analysis and Cox
      proportional hazard model analysis were performed. RESULTS: Between the Group I
      and II, cardiac events as well as chest pain symptoms, smoking, diabetic
      complications were significantly different (P < 0.05). On survival analysis,
      event free survival rate in Group II was significantly lower than in Group I (P =
      0.016). In univariate Cox proportional hazard analysis on overall cardiac event,
      Group (II over I), diabetic nephropathy, summed motion score (SMS), summed
      systolic thickening score (STS), numbers of abnormal segmental wall motion and
      systolic thickening predicted more cardiac events (P < 0.05). Multivariate
      analysis showed that STS was the only independent predictor cardiac event.
      CONCLUSION: The functional parameter, especially summed systolic thickening score
      on QG-SPECT had prognostic values, despite normal perfusion, in predicting
      cardiac events in diabetic patients, and QG-SPECT provides clinically useful risk
      stratification in diabetic patients with normal perfusion.

PMID- 24900102
TI  - Myocardial Blood Flow and Flow Reserve in Proximal and Mid-to-Distal Lesions of
      Left Anterior Descending Artery Measured By N-13 Ammonia PET/CT.
AB  - PURPOSE: The purpose of this study is to compare the myocardial blood flow (MBF)
      and flow reserve (MFR) between proximal and mid-to-distal lesions of the left
      anterior descending artery (pLAD and mdLAD, respectively) using N-13 ammonia
      positron emission tomography/computed tomography (PET/CT). METHODS: Subjects were
      11 patients (six men and five women, mean age 64.5 years) with known coronary
      artery disease (CAD) involving LAD studied by N-13 ammonia PET/CT. They were
      divided into two groups by the location of stenotic lesions, i.e. pLAD versus
      mdLAD. Global and regional MBF and MFR were measured and compared.
      Characteristics of perfusion defects including the number of involved segments,
      basal area involvement, location, size, and shape were also compared between the
      two groups. RESULTS: The regional MFR in mid-anterior segment was significantly
      lower in pLAD group (1.80 +/- 0.35 vs 2.76 +/- 1.13 for pLAD and mdLAD groups,
      respectively, p = 0.034), while global MFR was not different (2.10 +/- 1.10 vs
      2.34 +/- 0.84). Both stress and rest MBF in LAD territories were not different in
      both groups. The size of the perfusion defects were significantly larger in pLAD
      group (44.0 +/- 11.5 % vs 21.1 +/- 15.8 %, p = 0.041). Other characteristics such
      as location, basal area involvement, and shape were not significantly different
      between two groups. CONCLUSIONS: The proximal lesion makes lower MFR in the mid
      anterior segment and larger perfusion defect in the LAD territory but comparable
      MBF compared with mdLAD lesion.

PMID- 24900103
TI  - Detection and Characterization of Parathyroid Adenoma/Hyperplasia for
      Preoperative Localization: Comparison Between (11)C-Methionine PET/CT and (99m)Tc
      Sestamibi Scintigraphy.
AB  - PURPOSE: (11)C-Methionine PET/CT (Met-PET/CT) is a useful imaging method for
      detection of parathyroid adenoma; however, the reported detection rate has been
      variable. The current study was intended to investigate detection sensitivity and
      preoperative localization of parathyroid adenoma (PA) or parathyroid hyperplasia
      (PH) on Met-PET/CT compared with (99m)Tc-sestamibi (MIBI) scintigraphy in
      patients with primary hyperparathyroidism (HPT) or suspected PA. METHODS: Met
      PET/CT and MIBI scintigraphy images were reviewed by two nuclear medicine
      physicians unaware of pathologic results. Detection sensitivities and
      preoperative localization of detected parathyroid tissues into five predefined
      segments were evaluated by visual assessment and semi-quantitative analysis with
      ratio of standardized uptake values (SUVR) between parathyroid tissue and normal
      lung as reference. Linear regression analysis with SUVR and serum parathyroid
      hormone (sPTH) was performed for characterization of PA or PH. Predicted PTH
      (pPTH) was calculated and compared with sPTH in PH and PA. Each pPTH was obtained
      for a calculated SUVR by using linear regression model from the result of
      previous linear regression analysis between SUVR and sPTH. RESULTS: In 16
      patients, detection sensitivities of Met-PET/CT and MIBI scintigraphy were 91.7 %
      (11/12) and 41.7 % (5/12) for PA and PH including both biopsy-confirmed and
      clinically-suspected cases, and 100 % (8/8) and 50 % (4/8) for pathologically
      confirmed PA and PH cases only, respectively. Met-PET/CT showed higher
      performance than MIBI scintigraphy in localization of parathyroid tissues;
      correct localization rate was 87.5 % (7/8) on Met-PET/CT and 50 % (4/8) on MIBI
      scintigraphy. In semi-quantitative analysis, SUVR was linearly associated with
      sPTH by linear regression analysis (sPTH = 39.53 * SUVR - 89.84, p = 0.0383).
      There was a borderline significant difference in pPTH between PH and PA (35.1 vs
      204.7 +/- 164.0, p = 0.052), while there was no significant difference in sPTH
      between PH and PA (289 vs 230.4 +/- 160.4, p = 0.305). CONCLUSIONS: Met-PET/CT
      has a potential to be a useful diagnostic modality for preoperative detection and
      localization of parathyroid tissues with higher sensitivity than MIBI
      scintigraphy, and for characterization of PA or PH.

PMID- 24900104
TI  - Dynamic (18) F-FDG PET for Assessment of Tumor Physiology in Two Breast Carcinoma
      Xenografts.
AB  - PURPOSE: To compare dynamic 2-deoxy-2-[(18) F]fluoro-D-glucose positron emission
      tomography ((18) F-FDG PET) parameters in two selected human breast cancer
      xenografts and to evaluate associations with immunohistochemistry and histology.
      PROCEDURES: Dynamic (18) F-FDG PET of luminal-like MAS98.06 and basal-like
      MAS98.12 xenografts was performed, and the compartmental transfer rates (k 1 ,k 2
      ,k 3 ), blood volume fraction (v B ) and metabolic rate of (18) F-FDG(MR FDG )
      were estimated from pharmacokinetic model analysis. After sacrifice, analyses of
      hypoxia (pimonidazole), proliferation (Ki-67), vascularization (CD31), glucose
      transport receptor (GLUT1) and necrosis (HE) was performed. The level of
      hexokinase 2 (HK2) was estimated from Western blot analysis. RESULTS: The (18) F
      FDG uptake curves for the two xenografts were significantly different (p < 0.05).
      k 1 and v B were higher for MAS98.12 (p < 0.01), while k 3 was higher for
      MAS98.06 (p < 0.01). MAS98.12 had a higher fraction of stromal tissue and higher
      microvessel density (MVD), and it was less necrotic and hypoxic than MAS98.06.
      MAS98.12 had stronger positive GLUT1 staining and lower Ki-67 than MAS98.06. In
      both models significant correlations were found between k 1 and the GLUT1 score,
      between k 3 and the level of HK2, and between v B and MVD. CONCLUSIONS:
      Significant differences in dynamic (18) F-FDG parameters between the two human
      breast cancer xenografts were found. The differences could be explained by
      underlying histological and physiological characteristics.

PMID- 24900105
TI  - Clinical Usefulness of Serum CYFRA 21-1 in Patients with Colorectal Cancer.
AB  - PURPOSE: Among diverse tumor markers, pretreatment evaluation and follow-up
      detection of recurrence in colorectal cancer are generally evaluated by serum
      carcinoembryonic antigen (CEA) levels. However, there have been some reports
      about the low accuracy and high false-positive results of CEA in colorectal
      cancer. We investigated the clinical utilities of CYFRA 21-1 by comparing CEA and
      cancer antigen 19-9 (CA 19-9) in pretreatment and recurrent colorectal cancer.
      METHODS: Using a solid-phase immunoradiometric assay, serum levels of CYFRA 21-1,
      CEA and CA 19-9 were analyzed in 132 patients with primary colorectal cancer, 124
      healthy controls, 104 patients with benign colorectal disease and 19 patients
      with recurrent colorectal cancer. We determined three different cutoff values to
      evaluate the sensitivity of diagnostic performance in pretreatment and recurrent
      colorectal cancer. RESULTS: CYFRA 21-1 (>= 1.13 ng/ml) had a sensitivity of 47 %,
      compared with 37 % for CEA (>= 3.05 ng/ml) and 32.6 % for CA 19-9 (>= 23.1 ng/ml)
      in the initial staging of primary colorectal cancer. Using different cutoff
      values, CYFRA 21-1 showed higher sensitivity for pretreatment colorectal cancer
      than CEA and CA 19-9 in adenocarcinoma and adenosquamous carcinoma of this study.
      A mildly significant correlative relationship was noted between Dukes' stages and
      three tumor markers (p < 0.01). The areas under the receiver operating
      characteristic curves of CYFRA 21-1, CEA and CA 19-9 were 0.81 +/- 0.03, 0.74 +/-
      0.03 and 0.62 +/- 0.04, respectively, for discriminating colorectal cancer
      patients from patients with benign colorectal disease. In addition, CYFRA 21-1
      was determined as the most sensitive tumor marker for evaluating recurrent
      colorectal cancer for all cutoff values. CONCLUSION: This study showed that CYFRA
      21-1 could be a useful and dependable tumor marker for pretreatment and recurrent
      colorectal cancer. Further prospective studies on its usefulness with respect to
      the prognosis and utility of combined tumor markers are needed.

PMID- 24900106
TI  - Parametric Cerebrovascular Reserve Images Using Acetazolamide (99m)Tc-HMPAO
      SPECT: A Feasibility Study of Quantitative Assessment.
AB  - PURPOSE: Basal/acetazolamide stress (99m)Tc-HMPAO single-photon emission computed
      tomography (SPECT) has been widely used for evaluation of hemodynamics; however,
      qualitative and subjective visual assessment of cerebrovascular reserve (CVR) has
      been performed in clinical settings. The aim of this study was to generate
      parametric CVR images and evaluate its feasibility of quantification. METHODS:
      Basal/acetazolamide stress (99m)Tc-HMPAO SPECT data from 17 patients who
      underwent bypass surgery or percutaneous transluminal angioplasty were used.
      Spatial normalization was performed and parametric CVR images were generated
      using relative CVR (rCVR) of each voxel proportional to CVR of the whole brain.
      Binary parametric maps to show area of relatively reduced CVR were generated also
      using threshold of rCVR < 90 %. We calculated rCVR of internal carotid artery
      (ICA) using the parametric CVR images and probabilistic maps for ICA territory.
      Pre- and postprocedural parametric CVR images were obtained and quantitative
      rCVRs were compared. The rCVRs were evaluated according to visual grades for
      regional decreased CVR. RESULTS: Postprocedural rCVR obtained from parametric CVR
      images increased significantly from preprocedural rCVR. The rCVR was
      significantly correlated with visual grades of reduced CVR for each side of ICA
      territories. CONCLUSIONS: We generated parametric CVR images for
      basal/acetazolamide stress (99m)Tc-HMPAO SPECT. As a quantitative measurement,
      rCVR obtained from the parametric image was feasibly assessed hemodynamic
      abnormalities with preserved anatomical information.

PMID- 24900107
TI  - Myocardial Fibrosis in Hypertrophic Cardiomyopathy Demonstrated by Integrated
      Cardiac F-18 FDG PET/MR.
AB  - Hypertrophic cardiomyopathy (HCM) is a common condition defined as a diffuse or
      segmental left ventricular (LV) hypertrophy with a nondilated and hyperdynamic
      chamber as well as cardiac arrhythmias. Cardiac MR (CMR) imaging is a key
      modality for evaluation of HCM. In addition to the assessment of LV wall
      thickness, LV function and aortic flow, CMR is capable of estimation of late
      gadolinium enhancement (LGE) in affected myocardium which has been shown to have
      a direct correlation with incidence and severity of arrhythmias in HCM. In
      patients with HCM, LGE on CMR is presumed to represent intramyocardial fibrosis.
      Meanwhile, F-18 FDG myocardial PET has been sporadically studied in HCM, mostly
      for evaluation of the metabolic status of a hypertrophic myocardial segment,
      especially after interventions or to demonstrate partial myocardial fibrosis. We
      presented here the case of a 25-year-old male patient referred for simultaneous F
      18 FDG cardiac PET/MR for the evaluation of septal hypertrophy. The PET/MR
      revealed myocardial fibrosis in the septum associated with FDG-defect and LGE. 

PMID- 24900108
TI  - An unusual case of anaphylaxis after fluorine-18-labeled fluorodeoxyglucose
      injection.
AB  - [(18)F]FDG (fluorine-18 fluoro-2-deoxy-D-glucose) positron emission tomography
      (PET) is used worldwide for oncologic and neurologic applications. To date, the
      potential harm caused by [(18)F]FDG has focused on its radiation exposure effects
      rather than on its pharmacological effects. While an allergic response in the
      form of a skin manifestation has been reported after exposure to [(18)F]FDG, this
      report describes the first case of hypotension following exposure to this tracer.
      Here, the development of anaphylaxis after [(18)F]FDG injection is described. 

PMID- 24900109
TI  - Unsuspected Active Sarcoidosis Diagnosed by 18F-FDG PET/CT During the Search for
      a Primary Tumour in a Patient with Bone Lesions.
AB  - Sarcoidosis is a systemic chronic inflammatory disease of unknown aetiology,
      characterised by granulomatous lesions with heterogeneous clinical manifestations
      affecting multiple organs and tissues. Although the respiratory system is most
      commonly affected, the disease may also present with bone lesions. We report the
      case of a 31-year-old woman who presented with low back pain and no history of
      cancer and who was found to have suspicious lesions involving the entire spine on
      magnetic resonance imaging (MRI). The patient underwent 18F-fluorodeoxyglucose
      (FDG) PET/CT to search for a primary tumour and for staging purposes. 18F-FDG
      PET/CT revealed a pattern of hypermetabolic activity in widespread skeletal
      lesions and in a single left cervical lymph node. The primary tumour was not
      found, thus suggesting a haematologic disorder. Subsequent biopsies of a cervical
      lymph node and of bone tissue from L4 revealed active sarcoidosis with no
      evidence of cancer. This underlines the importance of considering all
      alternatives when hypermetabolic lesions are found on 18F-FDG PET/CT.
      Furthermore, 18F-FDG PET can be very useful to indicate accessible sites for
      guiding fine-needle aspiration cytology (FNAC). 

PMID- 24900110
TI  - Diffuse Myocardial Uptake of (99m)Tc-HDP in Multiple Myeloma.
AB  - Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of
      2%. Although the mechanism has not yet been fully clarified, several causes have
      been reported for this unusual uptake pattern. This paper presents a case of
      diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate
      ((99m)Tc-HDP) without either solid/visceral organ or soft tissue with multiple
      myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and
      chronic heart failure for 14 years underwent bone scanning due to a 2-month
      history of back pain within a 1-year period of MM. Three hours later, (99m)Tc-HDP
      late static images showed diffuse myocardial radiotracer accumulation and there
      were no other sites of abnormal soft tissue or visceral uptake. Myocardial
      accumulation had disappeared on 24-h delayed static images. This accumulation was
      thought to be related with AL-type amyloidosis associated with MM. 

PMID- 24900111
TI  - Usefulness of (18)F-FDG-PET/CT in Evaluating a Brainstem Glioma in an Adult
      Patient with Neurofibromatosis Type 1.

PMID- 24900112
TI  - Dual Tracer PET Imaging with FDG and FLT Differentiates Tuberculous
      Lymphadenopathy from Metastases in a Case of Carcinoma Cervix.

PMID- 24900113
TI  - Non-visualized Thyroid Gland by Tc-99m MIBI Scan with Normal Thyroid Scan.

PMID- 24900114
TI  - Multifocal Head and Neck Paraganglioma Evaluated with Different PET Tracers:
      Comparison Between Fluorine-18-Fluorodeoxyglucose and Gallium-68-Somatostatin
      Receptor PET/CT.

PMID- 24900115
TI  - Biliary Flow in Septate Gallbladder on Hepatobiliary Scintigraphy with SPECT/CT.

PMID- 24900116
TI  - Pyelo-cystic Reflux in F-18 FDG PET Scan Due to Ureteral Obstruction.

PMID- 24900117
TI  - The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on
      Physiologic Myocardial (18)F-FDG Uptake in Normal Humans.
AB  - PURPOSE: In a whole-body (18)F-FDG PET/CT, non-specific (18)F-FDG uptake of the
      myocardium is a common finding and can be very variable, ranging from background
      activity to intense accumulation and inhomogeneity. We investigated the effect of
      energy substrates and plasma/serum hormones that may have an influence on
      myocardial (18)F-FDG uptake. METHODS: F-FDG PET/CT was performed on 100 normal
      volunteers from November 2007 to August 2008. Blood samples were taken just
      before (18)F-FDG injection from all subjects. Myocardial (18)F-FDG uptake was
      measured as the mean (SUVmean) and maximal (SUVmax) standardized uptake value.
      The myocardium was delineated on the PET/CT image by a manual volume of interest
      (VOI). We analyzed the influence of age, sex, presence of diabetes, fasting
      duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA),
      epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free
      thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI).
      RESULTS: Overall, 92 subjects (mean age 50.28 +/- 8.30, male 57) were enrolled.
      The average of myocardial SUVmean was 2.08 and of myocardial SUVmax was 4.57,
      respectively and there was a strong linear correlation between SUVmean and SUVmax
      (r = 0.98). FFA and fasting duration showed significant negative correlation with
      myocardial (18)F-FDG uptake, respectively (r = -0.40 in FFA; r = -0.41 in fasting
      duration). No significant relationships were observed between myocardial uptake
      and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate,
      EPi, NEp, free T3, free T4, TSH and BMI. CONCLUSION: Myocardial (18)F-FDG uptake
      decreases with longer fasting duration and higher FFA level in normal humans.
      Modulating myocardial uptake could improve (18)F-FDG PET/CT imaging for specific
      oncologic and cardiovascular indications.

PMID- 24900118
TI  - Heterogeneity Analysis of (18)F-FDG Uptake in Differentiating Between Metastatic
      and Inflammatory Lymph Nodes in Adenocarcinoma of the Lung: Comparison with Other
      Parameters and its Application in a Clinical Setting.
AB  - PURPOSE: Lymph node (LN) characterization is crucial in determining the stage and
      treatment decisions in patient with lung cancer. Although (18)F
      fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG
      PET/CT) has a higher diagnostic accuracy in LN characterization than anatomical
      imaging, differentiating between metastatic and inflammatory LNs is still
      challenging because both could show high (18)F-FDG uptake. The purpose of this
      study was to assess if the heterogeneity of the (18)F-FDG uptake could help in
      differentiating between inflammatory and metastatic LNs in lung cancer, and to
      compare with other parameters. METHODS: A total of 44 patients with
      adenocarcinoma of the lung, who underwent preoperative (18)F-FDG PET/CT without
      having any previous treatments and were revealed to have (18)F-FDG-avid LNs, were
      enrolled. There were 52 pathology-proven metastatic lymph nodes in 26 subjects.
      The pathology-proven metastatic LNs were compared with 42 pathology-proven
      inflammatory/benign LNs in 18 subjects. The coefficient of variation (CV) was
      used to assess the heterogeneity of (18)F-FDG uptake by dividing the standard
      deviation of standardized uptake value (SUV) by mean SUV. The volume of interest
      was manually drawn based on the combined CT images of (18)F-FDG PET/CT (no
      threshold is used). Comparisons were made with the maximum standardized uptake
      values (SUVmax), visual assessment of (18)F-FDG uptake, longest diameter, and
      maximum Hounsfield units (HUmax). RESULTS: Metastatic lymph nodes tended to have
      higher CVs than the inflammatory LNs. The mean CV of metastatic LNs (0.30 +/-
      0.08; range: 0.08-0.55) was higher than that of inflammatory LNs (0.17 + 0.06;
      range, 0.07-0.32; P < 0.0001). On receiver operating characteristic (ROC) curve
      analysis, the area under curve was 0.901, and using 0.20 as cut-off value,
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and accuracy were 88.5 %, 76.2 %, 82.2 %, 84.3, and 83.0 %
      respectively. Accuracy of CV was slightly higher than SUVmax and diameter, but
      significantly higher than visual assessment and HUmax. CONCLUSIONS: In patients
      with adenocarcinoma of the lung having no prior treatments, metastatic LNs showed
      more heterogeneous (18)F-FDG uptake than inflammatory LNs. Measuring the CV of
      the SUV derived from a manual volume of interest (VOI) can be helpful in
      determining metastatic LN of adenocarcinoma of the lung. Including diagnostic
      criteria of CV into the diagnostic approach can increase the accuracy of
      mediastinal node status.

PMID- 24900119
TI  - The Value of F-18 FDG PET for Planning Treatment and Detecting Recurrence in
      Malignant Salivary Gland Tumors: Comparison with Conventional Imaging Studies.
AB  - PURPOSE: To assess the value of F-18 FDG PET/CT for detecting cervical lymph node
      (LN) metastasis and recurrence, as well as planning treatment, and to compare the
      accuracy of PET/CT with conventional imaging studies (CIS) in patients with
      malignant salivary gland tumor (SGT). METHODS: Staging and follow-up PET/CT for
      SGT were retrospectively reviewed. Enhanced CT and/or MRI of the neck were
      performed within 1 month of PET/CT. Final diagnosis was based on histology from
      cervical LN dissection and biopsy or a minimum 6 months of clinical and imaging
      follow-up. We compared the performance of PET/CT in initial cervical LN staging
      and recurrence detection with that of CIS. RESULTS: A total of 184 PET/CT exams
      of 66 patients were included, and 34 initial staging and 150 surveillance PET/CT
      exams were performed. The initial cervical LN detection sensitivity, specificity,
      accuracy, positive predictive value, and negative predictive value were 60.9 %,
      89.2 %, 84.0 %, 56.0 %, and 91.0 % for visual analysis on PET/CT, 39.1 %, 95.0 %,
      84.8 %, 64.3 %, and 87.4 % for semiquantitative analysis on PET/CT, and and 43.5
      %, 94.1 %, 84.8 %, 62.5 %, and 88.1 % for CIS. The sensitivity of visual analysis
      on PET/CT was significantly higher than that of semiquantitative analysis on
      PET/CT and CIS (p = 0.0009 and 0.0086). In 5 of 34 initial staging patients (14.7
      %), the treatment plan was changed from curative surgery to palliative therapy.
      The performance of follow-up PET/CT showed no significant difference compared
      with CIS. CONCLUSION: PET/CT showed comparable performance with CIS for cervical
      LNs staging. Initial PET/CT changed treatment plans in 14.7 % of patients.
      However, PET/CT offered no additional advantage for detecting locoregional
      recurrence.

PMID- 24900120
TI  - (18)F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma:
      Differential Features According to Expression of Anaplastic Lymphoma Kinase.
AB  - PURPOSE: Primary systemic anaplastic large cell lymphoma (ALCL) is divided into
      two entities according to the expression of anaplastic lymphoma kinase (ALK). We
      investigated (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG
      PET) findings in primary systemic ALCL according to ALK expression. METHODS:
      Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide,
      doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled.
      Among them, patients who underwent interim and/or post-therapy PET were further
      investigated for the treatment response and survival analysis. Baseline PET was
      analyzed visually and semi-quantitatively using peakSUV, and interim and post
      therapy PETs were visually analyzed. RESULTS: All cases were (18)F-FDG-avid on
      baseline PET. The peakSUV of ALK-positive ALCL (n = 16, 18.7 +/- 10.5) was higher
      than that of ALK-negative ALCL (n = 21, 10.0 +/- 4.9) (P = 0.006). In ALK
      negative ALCL, complete response (CR) rate in negative-interim PET was higher
      than positive-interim PET (100 % vs 37.5 %, P = 0.02); however, there was no such
      difference in ALK-positive ALCL (100 % vs 75 %, P = 0.19). The 3-year progression
      free survival (PFS) was not significantly different between ALK-positive and ALK
      negative ALCL (72.7 % vs 47.6 %, P = 0.34). In ALK-negative ALCL, negative
      interim and post-therapy PET patients had better 3-year PFS than positive interim
      (83.3 % vs 25.0 %, P = 0.06) and post-therapy PET patients (70.0 % vs 20.0 %, P =
      0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET
      results. CONCLUSIONS: On baseline PET, all cases showed (18)F-FDG-avidity, and
      ALK expression was related to higher (18)F-FDG uptake. ALK-positive patients tend
      to have better PFS than ALK-negative patients. Negative-interim PET was a good
      indicator of CR, and interim or post-therapy PET was helpful for predicting the
      prognosis only in the ALK-negative group.

PMID- 24900122
TI  - The Prognostic Value of (18)F-FDG PET/CT for Early Recurrence in Operable Breast
      Cancer: Comparison with TNM Stage.
AB  - PURPOSE: We evaluated whether the maximum standardized uptake values (SUVmax) of
      primary tumor from the initial staging by (18)F-fluorodeoxyglucose positron
      emission tomography/computed tomography ((18)F-FDG PET/CT) of patients with
      breast cancer could identify patients at risk for early recurrence within 2
      years, particularly in comparison to the American Joint Committee on Cancer
      (AJCC) stage. METHODS: We reviewed the staging (18)F-FDG PET/CT images of
      patients with primary breast cancer and their medical records. The SUVmax of the
      primary tumor was measured. The presence or absence of FDG uptake in the axillary
      lymph node (ALN) was also assessed. The patient's pathologic primary tumor stage
      (pT), pathologic regional lymph node stage (pN), stage grouping, age, estrogen
      receptor (ER) and progesterone receptor (PR) status, and neoadjuvant chemotherapy
      history were evaluated with the FDG uptake parameters for recurrence within 2
      years following the end of first-line therapy. RESULTS: Recurrence within 2 years
      was present in 9.1 % (n = 40) out of the 441 patients assessed. The FDG uptake in
      ALN, pT, pN, stage grouping and neoadjuvant chemotherapy history were prognostic
      for early recurrence, while primary tumor SUVmax, age, and ER or PR status were
      not significant on logistic regression. On multivariate analysis, only the stage
      grouping (odds ratio 2.79; 95 % CI 1.73, 4.48; p < 0.0001) and neoadjuvant
      chemotherapy history (odds ratio 2.70; 95 % CI 1.22, 5.98; p = 0.0141) could
      identify patients at increased risk for recurrence within 2 years. CONCLUSIONS:
      Primary tumor FDG uptake measured by SUVmax, and visual assessment of FDG uptake
      in the ALN in the initial staging PET/CT of patients with breast cancer may not
      have additional prognostic value compared with the AJCC stage grouping for early
      recurrence.

PMID- 24900121
TI  - Prognostic Value of Metabolic Activity Measured by (18)F-FDG PET/CT in Patients
      with Advanced Endometrial Cancer.
AB  - PURPOSE: We evaluated the potential prognostic value of (18)F-fluorodeoxyglucose
      (FDG) positron emission tomography/computed tomography (PET/CT) in patients with
      stage IIIC/IV endometrial cancer. METHODS: Patients with stage IIIC/IV
      endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled.
      Maximum standardized uptake values (SUVmax) measured from regions of interest
      (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with
      overall survival (OS). The SUVn was defined as the highest SUVmax of the
      metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier
      method. RESULTS: A total of 42 patients with a median age of 55.5 years (range 32
      76 years) were included. Twenty-nine percent (n = 12) of patients were
      premenopausal and 71 % (n = 30) were postmenopausal. The average SUVt was 12.9
      (range 1.8-36.5), and the average SUVn was 7.3 (range 2.0-22.5). Median follow-up
      time was 25.9 months (range 1-84 months). Using a SUVt of 9.5 as a cutoff value,
      two groups with different rates were determined (P = 0.026). In addition,
      patients with a low SUVn had significantly better OS than those with a high SUVn
      (P = 0.003). Patients in the International Federation of Obstetrics and
      Gynecology (FIGO) stage IV group with SUVt >= 9.5 or SUVn >= 7.3 showed a
      significantly longer OS than the other groups. CONCLUSIONS: FDG uptake of primary
      endometrial cancer and lymph nodes might be a prognostic factor in advanced
      endometrial cancer. More aggressive therapy could be considered in patients with
      stage IV endometrial cancer and high SUVt and/or high SUVn.

PMID- 24900123
TI  - Limited clinical value of periablative changes of serum markers in the prediction
      of biochemical remission in patients with papillary thyroid cancer.
AB  - PURPOSE: Remnant thyroid ablation and 1-year stimulated thyroglobulin (sTg)
      measurement are recommended for those who have undergone total thyroidectomy for
      differentiated thyroid cancer. The serum Tg kinetics in such patients are still
      unclear. This study was designed to evaluate whether the periablative change in
      serum markers can predict biochemical remission in papillary thyroid cancer (PTC)
      patients. METHODS: We reviewed the medical records of 185 patients who were given
      high-dose radioactive iodine ablation therapy from January 2006 to December 2008.
      Serum Tg, TSH, and anti-Tg antibody (TgAb) were measured on the day and the
      following 10th day of radioactive iodine administration. We defined preablative
      sTg as Tg-1, postablative Tg measured on the 10th day of ablation as Tg-2, and
      the 1-year sTg as Tg-3. DeltaTg means Tg2-Tg1. The same definition was applied to
      TgAb. RESULTS: A biochemical remission defined as Tg-3 < 2 ng/ml was achieved in
      144 patients. Among the patients who achieved biochemical remission, PTC recurred
      in six during a median follow-up of 54 months. Tg-1 < 3.3 ng/ml (p < 0.0001)
      predicted biochemical remission. Neither the DeltaTg nor DeltaTgAb was useful for
      predicting biochemical remission. On the evaluation of recurrence after
      biochemical remission, Tg-1 > 5.32 (p < 0.0001) and Tg-3 > 2.9 (p = 0.01) were
      proven to be statistically significant cutoff values for predicting recurrence.
      The DeltaTg and DeltaTgAb were not able to predict recurrence. CONCLUSION: For
      the prediction of biochemical remission or recurrence after biochemical
      remission, preablative sTg was demonstrated to be a statistically significant
      serum marker. However, short-term changes in biochemical markers including Tg and
      TgAb around the day of ablation could not provide useful clinical information
      about biochemical remission or disease recurrence. In conclusion, 1-year sTg
      measurement cannot be omitted with short-term change.

PMID- 24900124
TI  - Characteristic uptake pattern of bone scintigraphy in patients with
      hepatocellular carcinoma following treatment with high-intensity focused
      ultrasound.
AB  - PURPOSE: This study retrospectively reviews the characteristic bone scintigraphic
      findings in 18 patients with hepatocellular carcinoma (HCC) following treatment
      with high-intensity focused ultrasound (HIFU). A potential complication of HIFU
      is damage to the tissues along the path of the ultrasound beam and structures
      superficial to the lesion of interest. METHODS: Patients with hepatocellular
      carcinoma who underwent a bone scan between 1st December 2005 and 31st December
      2011 were considered for this study. Among these patients, only those who had
      bone scans after the HIFU treatment were included. The time between HIFU
      treatment and bone scans, HIFU energy, HCC sites, tumour sizes and related
      radiological findings were evaluated. RESULTS: In total, 20 bone scans of 18
      patients were reviewed. Of these scans, two patients were normal; three patients
      showed decreased uptake, four patients showed increased uptake and nine patients
      showed mixed uptakes of the bony tracer in their rib cages. The defects were
      located in the anterior, lateral, anterolateral or posterolateral aspects of the
      rib cage. The majority of those cold defects were in the right anterior rib
      cages. SPECT/CT was used to localise the decreased uptake in ribs. The magnetic
      resonance imaging in individual patients invariably showed ill-defined rim
      enhancement along the right chest wall, signifying chest wall injury.
      CONCLUSIONS: The results showed that tissue ablation using HIFU caused tissue
      injury along the pathway of high-intensity ultrasound beams. The harm to tissues
      is presented as photopenic area on the rib cages due to necrosis or hot spots due
      to rib fractures in the bone scan. Since these cold defects are subtle, they are
      easily overlooked or mistaken as aggressive bony metastasis.

PMID- 24900125
TI  - Conversion to Paradoxical Finding on Technetium-99m-labeled RBC Scintigraphy
      after Treatment for Secondary Raynaud's Phenomenon.
AB  - An 18-year-old woman reported that after exposure to cold temperatures her
      fingers appeared blue and her hands and feet felt cold. Secondary Raynaud's
      phenomenon (RP) associated with peripheral vascular disease was suspected.
      Technetium (Tc)-99m-labeled RBC hand scintigraphy after cold change showed
      decreased blood pool activity in her fingers. The patient's symptoms improved
      after she received sarpogrelate HCL (200 mg/day) and nifedifine (40 mg/day).
      Follow-up scintigraphy performed 7 months after the patient started treatment
      showed paradoxically increased blood pool activity in her fingers after cold
      challenge. To the best of our knowledge, this is the first case report of a
      patient with secondary RP showing paradoxical change on scintigraphy after she
      received medication that improved her symptoms. 

PMID- 24900126
TI  - Radioimmunotherapy with (131)i-rituximab in a patient with diffuse large B-cell
      lymphoma relapsed after treatment with (90)y-ibritumomab tiuxetan.
AB  - We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with
      radioiodinated rituximab ((131)I-rituximab) for relapsed diffuse large B-cell
      lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a
      complete response (CR) after six cycles of R-CHOP (rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed
      20 months later. Although the patient had achieved a second and a third CR after
      two cycles of (90)Y-ibritumomab tiuxetan, he experienced a third relapse
      approximately 3 years later. Between March and June 2011, the patient received
      three cycles of (131)I-rituximab. Although he had achieved partial response after
      the second cycle, the disease progressed after the third cycle, and the total
      progression-free survival was thus 5 months. The patient suffered only relatively
      mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with (131)I
      rituximab is therefore potentially effective in patients with relapsed DLBCL,
      even after the failure of (90)Y-ibritumomab tiuxetan therapy. 

PMID- 24900127
TI  - Skin Manifestation of Unsuspecting Prostate Cancer Detected by 18F-FDG PET/CT
      Performed To Assess Underlying Multiple Myeloma.
AB  - BACKGROUND: Skin metastases from either prostate adenocarcinoma or multiple
      myeloma rarely occur. We report the case of a 73-year-old man with multiple
      myeloma who presented with multiple subcutaneous nodules 3 years after his
      initial diagnosis. METHODS: Fluorine-18 fluorodeoxyglucose (18F-FDG) positron
      emission tomography/computed tomography (PET/CT) imaging was suggestive of a
      concomitant second primary from the prostate. RESULTS: This case highlights not
      only a rare initial manifestation of prostate cancer, but also the role of 18F
      FDG-PET/CT in detecting a clinically unsuspected second malignancy. CONCLUSION:
      It potentially corroborates the possible association of both diseases, as has
      been reported before.

PMID- 24900128
TI  - Toxoplasmic Lymphadenitis Mimicking a Metastatic Thyroid Carcinoma at (18)F-FDG
      PET/CT.

PMID- 24900129
TI  - Global Hepatic Uptake of (99m)Tc-MAA During VQ Scintigraphy Secondary to
      Synchronous Superior and Inferior Vena Caval Obstruction: a Demonstration of
      Trans-Portal Venous Collateral Pathways.

PMID- 24900130
TI  - Low-dose adefovir-induced hypophosphatemic osteomalacia on whole-body bone
      scintigraphy.

PMID- 24900131
TI  - Additional Detection of Multiple Osteomas in a Patient with Gardner's Syndrome by
      Bone SPECT/CT.

PMID- 24900132
TI  - (18)F-FDG PET-CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by
      (18)F-FDOPA PET-CT.

PMID- 24900134
TI  - Intratumoral Metabolic Heterogeneity for Prediction of Disease Progression After
      Concurrent Chemoradiotherapy in Patients with Inoperable Stage III Non-Small-Cell
      Lung Cancer.
AB  - PURPOSE: We evaluated the value of variable (18)F-FDG PET/CT parameters for the
      prediction of disease progression after concurrent chemoradiotherapy (CCRT) in
      patients with inoperable stage III non-small-cell lung cancer (NSCLC). METHODS:
      One hundred sixteen pretreatment FDG PET/CT scans of inoperable stage III NSCLC
      were retrospectively reviewed (stage IIIA: 51; stage IIIB: 65). The volume of
      interest was automatically drawn for each primary lung tumor, and PET parameters
      were assessed as follows: maximum standardized uptake value (SUVmax), metabolic
      tumor volume (MTV) using the boundaries presenting SUV intensity exceeding 3.0,
      and the area under the curve of the cumulative SUV-volume histograms (AUC-CSH),
      which is known to reflect the tumor heterogeneity. Progression-free survival
      (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free
      survival (DMFS) were compared with each PET and clinical parameters by univariate
      and multivariate survival analysis. RESULTS: In the ROC analysis, the optimal
      cutoff values of SUVmax, MTV (cm(3)), and AUC-CSH for prediction of PFS were
      determined as 21.5, 27.7, and 4,800, respectively. In univariate analysis, PFS
      was statistically significantly reduced in those with AUC-CSH < 4,800 (p =
      0.004). In multivariate analysis, AUC-CSH and SUVmax were statistically
      significant independent prognostic factors (HR 3.35, 95 % CI 1.79-6.28, p <
      0.001; HR 0.25, 95 % CI 0.09-0.70, p = 0.008, respectively). Multivariate
      analysis showed that AUC-CSH was the most significant independent prognostic
      factor for LRFS and DMFS (HR 3.27, 95 % CI 1.54-6.94, p = 0.002; HR 2.79, 95 % CI
      1.42-5.50, p = 0.003). CONCLUSIONS: Intratumoral metabolic heterogeneity of
      primary lung tumor in (18)F-FDG PET/CT can predict disease progression after CCRT
      in inoperable stage III NSCLC.

PMID- 24900135
TI  - Evaluation of Dixon Sequence on Hybrid PET/MR Compared with Contrast-Enhanced
      PET/CT for PET-Positive Lesions.
AB  - PURPOSE: Hybrid positron emission tomography and magnetic resonance (PET/MR)
      imaging performs a two-point Dixon MR sequence for attenuation correction.
      However, MR data in hybrid PET/MR should provide anatomic and morphologic
      information as well as an attenuation map. We evaluated the Dixon sequence of
      hybrid PET/MR for anatomic correlation of PET-positive lesions compared with
      contrast-enhanced PET/computed tomography (CT) in patients with oncologic
      diseases. METHODS: Twelve patients underwent a single injection, dual imaging
      protocol. PET/CT was performed with an intravenous contrast agent (85 +/- 13 min
      after (18)F-FDG injection of 403 +/- 45 MBq) and then (125 +/- 19 min after
      injection) PET/MR was performed. Attenuation correction and anatomic allocation
      of PET were performed using contrast-enhanced CT for PET/CT and Dixon MR sequence
      for hybrid PET/MR. The Dixon MR sequence and contrast-enhanced CT were compared
      for anatomic correlation of PET-positive lesions (scoring scale ranging from 0 to
      3 for visual ratings). Additionally, standardized uptake values (SUVs) for the
      detected lesions were assessed for quantitative comparison. RESULTS: Both hybrid
      PET/MR and contrast-enhanced PET/CT identified 55 lesions with increased FDG
      uptake in ten patients. In total, 28 lymph nodes, 11 bone lesions, 3 dermal
      nodules, 3 pleural thickening lesions, 2 thyroid nodules, 1 pancreas, 1 liver, 1
      ovary, 1 uterus, 1 breast, 1 soft tissue and 2 lung lesions were present. The
      best performance was observed for anatomic correlation of PET findings by the
      contrast-enhanced CT scans (contrast-enhanced CT, 2.64 +/- 0.70; in-phase, 1.29
      +/- 1.01; opposed-phase, 1.29 +/- 1.15; water-weighted, 1.71 +/- 1.07; fat
      weighted, 0.56 +/- 1.03). A significant difference was observed between the
      scores obtained from the contrast-enhanced CT and all four coregistered Dixon MR
      images. Quantitative evaluation revealed a high correlation between the SUVs
      measured with hybrid PET/MR (SUVmean, 2.63 +/- 1.62; SUVmax, 4.30 +/- 2.88) and
      contrast-enhanced PET/CT (SUVmean, 3.88 +/- 2.30; SUVmax, 6.53 +/- 4.04) in PET
      positive lesions (SUVmean, rho = 0.93; SUVmax, rho = 0.95), although hybrid
      PET/MR presented a decrease of SUVs compared with contrast-enhanced PET/CT (mean
      reduction; SUVmean, 32.44 +/- 15.64 %; SUVmax, 35.16 +/- 12.59 %). CONCLUSIONS:
      Despite different attenuation correction approaches, the SUV of PET-positive
      lesions correlated well between hybrid PET/MR and contrast-enhanced PET/CT.
      However Dixon MR images acquired for attenuation correction were insufficient to
      provide anatomic information of PET images because of low spatial resolution.
      Thus, additional MR sequence with fast and higher resolution may be necessary for
      anatomic information.

PMID- 24900133
TI  - Recent Trends in PET Image Interpretations Using Volumetric and Texture-based
      Quantification Methods in Nuclear Oncology.
AB  - Image quantification studies in positron emission tomography/computed tomography
      (PET/CT) are of immense importance in the diagnosis and follow-up of variety of
      cancers. In this review we have described the current image quantification
      methodologies employed in (18)F-fluorodeoxyglucose ((18)F-FDG) PET in major
      oncological conditions with particular emphasis on tumor heterogeneity studies.
      We have described various quantitative parameters being used in PET image
      analysis. The main contemporary methodology is to measure tumor metabolic
      activity; however, analysis of other image-related parameters is also increasing.
      Primarily, we have identified the existing role of tumor heterogeneity studies in
      major cancers using (18)F-FDG PET. We have also described some newer
      radiopharmaceuticals other than (18)F-FDG being studied/used in the management of
      these cancers. Tumor heterogeneity studies are being performed in almost all
      major oncological conditions using (18)F-FDG PET. The role of these studies is
      very promising in the management of these conditions. 

PMID- 24900136
TI  - Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in
      Gastric Cancer.
AB  - PURPOSE: We performed this study to evaluate the predictive value of pretreatment
      F-18 FDG PET/CT for progression-free survival (PFS) in patients with gastric
      cancer. METHODS: Of 321 patients with a diagnosis of gastric cancer, we
      retrospectively enrolled 97 patients (men:women = 61:36, age 59.8 +/- 13.2
      years), who underwent pretreatment F-18 fluoro-2-deoxyglucose positron emission
      tomography/computed tomography (F-18 FDG PET/CT) from January 2009 to December
      2009. Maximum standardized uptake value (SUVmax) was measured for each case with
      detectable primary lesions. In the remaining non-detectable cases, SUVmax was
      measured from the corresponding site seen on gastroduodenoscopy for analysis. In
      subgroup analysis, metabolic tumor volume (MTV) was measured in 50 patients with
      clearly distinguishable primary lesions. SUVmax, stage, depth of tumor invasion
      and presence of lymph node metastasis were analyzed in terms of PFS. Receiver
      operating characteristic (ROC) curves were used to find optimal cutoff values of
      SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and
      PFS was analyzed using the Kaplan-Meier with log-rank test and Cox's proportional
      hazard regression methods. RESULTS: Of 97 patients, 15 (15.5 %) had disease
      progression. The mean follow-up duration was 29.6 +/- 10.2 months. The mean PFS
      of low SUVmax group (<=5.74) was significantly longer than that of the high
      SUVmax group (>5.74) (30.9 +/- 8.0 vs 24.3 +/- 13.6 months, p = 0.008). In
      univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2,
      T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs <=5.74) were
      significantly associated with recurrence. In multivariate analysis, high SUVmax
      (>5.74) was the only poor prognostic factor for PFS (p = 0.002, HR 11.03, 95 % CI
      2.48-49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was
      the only poor prognostic factor for PFS (p = 0.034, HR 3.59, 95 % CI 1.10-11.71).
      CONCLUSION: In gastric cancer, SUVmax measured by pretreatment F-18 FDG PET/CT
      has a significant predictive value for PFS. In addition, if MTV is measurable,
      high MTV is an independent factor for disease progression.

PMID- 24900137
TI  - Characteristics of Metastatic Mediastinal Lymph Nodes of Non-Small Cell Lung
      Cancer on Preoperative F-18 FDG PET/CT.
AB  - PURPOSE: The aim of this study was to evaluate the characteristics of PET and CT
      features of mediastinal metastatic lymph nodes on F-18 FDG PET/CT and to
      determine the diagnostic criteria in nodal staging of non-small cell lung cancer.
      METHODS: One hundred four non-small cell lung cancer patients who had
      preoperative F-18 FDG PET/CT were included. For quantitative analysis, the
      maximum SUV of the primary tumor, maximum SUV of the lymph nodes (SUVmax), size
      of the lymph nodes, and average Hounsfield units (aHUs) and maximum Hounsfield
      units (mHUs) of the lymph nodes were measured. The SUVmax, SUV ratio of the lymph
      node to blood pool (LN SUV/blood pool SUV), SUV ratio of the lymph node to
      primary tumor (LN SUV/primary tumor SUV), size, aHU, and mHU were compared
      between the benign and malignant lymph nodes. RESULTS: Among 372 dissected lymph
      node stations that were pathologically diagnosed after surgery, 49 node stations
      were malignant and 323 node stations benign. SUVmax, LN SUV/blood pool SUV, and
      size were significantly different between the malignant and benign lymph node
      stations (P < 0.0001). However, there was no significant difference in LN
      SUV/primary tumor SUV (P = 0.18), mHU (P = 0.42), and aHU (P = 0.98). Using
      receiver-operating characteristic curve analyses, there was no significant
      difference among these three variables (SUVmax, LN SUV/blood pool SUV, and size).
      The optimal cutoff values were 2.9 for SUVmax, 1.4 for LN SUV/blood pool SUV, and
      5 mm for size. When the cutoff value of SUVmax >=2.9 and size >=5 mm were used in
      combination, the positive predictive value was 44.2 %, and the negative
      predictive value was 90.9 %. When we evaluated the results based on the histology
      of the primary tumor, the negative predictive value was 92.3 % in adenocarcinoma
      (cutoff values of SUVmax >=2.3 and size >=5 mm) and 97.2 % in squamous cell
      carcinoma (cutoff values of SUVmax >=3.6 and size >=8 mm), separately.
      CONCLUSIONS: In the lymph node staging of non-small cell lung cancer, SUVmax, LN
      SUV/blood pool SUV, and size show statistically significant differences between
      malignant and benign lymph nodes. These variables can be used to differentiate
      malignant from benign lymph nodes. The combination of the SUVmax and size of
      lymph node might have a good negative predictive value.

PMID- 24900138
TI  - Automated Analysis of (123)I-beta-CIT SPECT Images with Statistical Probabilistic
      Anatomical Mapping.
AB  - BACKGROUND: Population-based statistical probabilistic anatomical maps have been
      used to generate probabilistic volumes of interest for analyzing perfusion and
      metabolic brain imaging. We investigated the feasibility of automated analysis
      for dopamine transporter images using this technique and evaluated striatal
      binding potentials in Parkinson's disease and Wilson's disease. MATERIALS AND
      METHODS: We analyzed 2beta-Carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane
      ((123)I-beta-CIT) SPECT images acquired from 26 people with Parkinson's disease
      (M:F = 11:15, mean age = 49 +/- 12 years), 9 people with Wilson's disease (M: F =
      6:3, mean age = 26 +/- 11 years) and 17 normal controls (M:F = 5:12, mean age =
      39 +/- 16 years). A SPECT template was created using striatal statistical
      probabilistic map images. All images were spatially normalized onto the template,
      and probability-weighted regional counts in striatal structures were estimated.
      The binding potential was calculated using the ratio of specific and nonspecific
      binding activities at equilibrium. Voxel-based comparisons between groups were
      also performed using statistical parametric mapping. RESULTS: Qualitative
      assessment showed that spatial normalizations of the SPECT images were successful
      for all images. The striatal binding potentials of participants with Parkinson's
      disease and Wilson's disease were significantly lower than those of normal
      controls. Statistical parametric mapping analysis found statistically significant
      differences only in striatal regions in both disease groups compared to controls.
      CONCLUSION: We successfully evaluated the regional (123)I-beta-CIT distribution
      using the SPECT template and probabilistic map data automatically. This procedure
      allows an objective and quantitative comparison of the binding potential, which
      in this case showed a significantly decreased binding potential in the striata of
      patients with Parkinson's disease or Wilson's disease.

PMID- 24900139
TI  - Difference of clinical and radiological characteristics according to radioiodine
      avidity in pulmonary metastases of differentiated thyroid cancer.
AB  - PURPOSE: To evaluate differences in clinical, radiological and laboratory
      findings between pulmonary metastasis with and without radioiodine avidity in
      thyroidectomized differentiated thyroid cancer (DTC) patients with pulmonary
      metastasis who underwent high-dose I-131 treatment. METHODS: A total of 105 DTC
      patients with pulmonary metastasis (age, 48.7 +/- 16.8 years; women/men, 78/27)
      were included. Clinical characteristics, chest computed tomography (CT), F-18
      fluorodeoxyglucose positron emission tomography (F-18 FDG PET)/CT and thyroid
      stimulating hormone (TSH)-stimulated serum thyroglobulin (s-Tg) level were
      compared between patients with and without radioiodine uptake in metastatic lung
      lesions. The response to I-131 treatment was evaluated with follow-up study.
      RESULTS: Eighty-nine patients (84.8 %, whole-body scan positive [WBSP] group)
      showed radioiodine uptake at pulmonary metastasis on post I-131 treatment whole
      body scan (WBS) and 16 patients (15.2 %, WBS negative [WBSN] group) did not show
      uptake at pulmonary lesions on the WBS. Ninety percent and 87 % of the WBSP group
      had visible metastatic lesions on CT and F-18 FDG PET/CT; however, all of the
      patients in the WBSN group showed lesions on CT and F-18 FDG PET/CT. In seven
      (6.7 %) of 105 patients, CT and F-18 FDG PET/CT could not detect pulmonary
      lesions, which were diagnosed by post I-131 treatment WBS. Complete disease
      remission was achieved in six (5.7 %) patients and all of them were in the WBSP
      group. CONCLUSIONS: Metastatic lesion was not visualized on chest CT or F-18 FDG
      PET/CT in 6.7 % of DTC patients with pulmonary metastasis and the lesion was
      visualized only on post I-131 treatment WBS. Complete remission was achieved in
      5.7 % of DTC patients with pulmonary metastasis and the cured metastases were non
      visualizing or micronodular lesions on chest CT and demonstrated radioiodine
      avidity on post I-131 treatment WBS.

PMID- 24900140
TI  - Clinical significance of diffuse intrathoracic uptake on post-therapy I-131 scans
      in thyroid cancer patients.
AB  - PURPOSE: The purpose of this study was to identify the frequency and possible
      cause of diffuse intrathoracic uptake on post-therapy I-131 scans in thyroid
      cancer patients. METHODS: We retrospectively reviewed 781 post-therapy scans of
      755 thyroid cancer patients who underwent total thyroidectomy and radioactive
      iodine therapy between January and December 2010. Diffuse intrathoracic uptake on
      post-therapy scans was examined, and clinical patient characteristics including
      sex, age, regimen for thyroid-stimulating hormone (TSH) stimulation (thyroid
      hormone withdrawal or recombinant human TSH injection), TSH, thyroglobulin (Tg)
      and anti-thyroglobulin antibody (anti-Tg Ab) levels, therapeutic dose of
      radioactive iodine therapy and prior history of radioactive iodine therapy were
      recorded.Scan findings were correlated with chest CT, chest radiographs,
      laboratory tests and/or clinical status. Diffuse intrathoracic uptake without
      evidence of pathologic condition was categorized as indeterminate. The
      association between clinical characteristics and intrathoracic uptake were
      analyzed for negative intrathoracic uptake and indeterminate uptake groups.
      RESULTS: Diffuse intrathoracic uptake on post-therapy scans was demonstrated in
      39 out of 755 (5.2 %) patients, among which 3 were confirmed as lung metastasis.
      The 14 patients that showed high Tg or anti-Tg Ab levels were considered to be at
      risk of having undetected micrometastasis on other imaging modalities. The
      remaining 22 were indeterminate (2.9 %).Upon comparison of negative intrathoracic
      uptake and indeterminate uptake groups, TSH stimulation by thyroid hormone
      withdrawal was shown to be significantly correlated with diffuse intrathoracic
      uptake (p < 0.05). CONCLUSION: The frequency of diffuse intrathoracic uptake on
      post-therapy scans was 5.2 % and could be seen in thyroid cancer patients with
      underlying lung metastasis as well as those without definite pathologic
      condition. In the latter, there was a higher frequency for diffusely increased
      intrathoracic uptake in those who underwent thyroid hormone withdrawal rather
      than recombinant human TSH injection.

PMID- 24900141
TI  - Impact of Nonosseous Findings on (18)F-NaF PET/CT in a Patient with Ductal Breast
      Carcinoma.
AB  - (18)F-NaF was used as a bone-seeking PET tracer for skeletal imaging until the
      introduction of the widely available (99m)Tc-labeled bone agents. However, there
      is renewed clinical interest in (18)F-NaF since prior technical and logistic
      limitations to its routine use are no longer present, and, as a consequence, it
      is likely that uptake unrelated to bone and non-osseous findings will be
      encountered more frequently. As a result of tumoral necrosis, soft tissue
      metastases may demonstrate (18)F-NaF avidity due to dystrophic calcification. On
      the other hand, all non-osseous findings, whether (18)F-NaF avid or not, may
      provide important diagnostic information that may alter the course of the
      disease, including treatment options. Herein we present a patient with ductal
      carcinoma of the breast in whom findings unrelated to the skeletal system in
      (18)F-NaF PET/CT altered the treatment strategy. 

PMID- 24900142
TI  - Integration of PET/CT in Current Diagnostic and Response Evaluation Methods in
      Patients with Tuberculosis.
AB  - Tuberculosis is a systemic disease that still affects many people. While pleural
      involvement is frequently observed in extrapulmonary tuberculosis, multiple
      skeletal system and articular involvements are quite rare. FDG PET imaging could
      be a promising diagnostic and treatment monitoring method, especially in
      complicated cases and if the other methods are inadequate. In this case study, we
      report a patient who was admitted with suspected malignancy and then diagnosed
      with tuberculosis pleuritis, lymphadenitis, spondylodiscitis, and sacroiliitis
      with specific symptoms; the response to anti-tuberculosis therapy was shown using
      FDG PET/CT. 

PMID- 24900143
TI  - An inflammatory dentigerous cyst shows rim uptake on bone scan: a case report.
AB  - Dentigerous cysts are developmental odontogenic jaw cysts, commonly manifesting
      in the 2nd and 3rd decades of life. This article presents an extremely rare case
      of dentigerous cyst showing increased uptake in the peripheral rim on bone scan.
      Herein, we discuss the clinical, radiographic, and histologic features of
      dentigerous cysts as well as the pathological mechanism underlying their
      activities on the bone scan. Bone scan was a sensitive tool for detecting the
      biologic activity of dentigerous cyst in our case. 

PMID- 24900144
TI  - Multiple Diagnostic Imaging of a Patient with Solid Pseudopapillary Tumour of the
      Pancreas: EUS, CT and FDG PET/CT.

PMID- 24900145
TI  - Metastatic Brachial Plexopathy in a Case of Recurrent Breast Carcinoma
      Demonstrated on (18)F-FDG PET/CT.

PMID- 24900146
TI  - Identification of Ambiguous Activities in Radionuclide Cisternography Using
      SPECT/CT: Aspirated and Ingested CSF Rhinorrhea.

PMID- 24900147
TI  - An Unusual Case of Plasmablastic Lymphoma Presenting as Paravertebral Mass
      Evaluated by (18) F-FDG PET/CT.

PMID- 24900148
TI  - Expression patterns of glucose transporter-1 gene and thyroid specific genes in
      human papillary thyroid carcinoma.
AB  - PURPOSE: The expression of glucose transporter-1 (Glut-1) gene and those of major
      thyroid-specific genes were examined in papillary carcinoma tissues, and the
      expressions of these genes were compared with cancer differentiation grades.
      MATERIALS AND METHODS: Twenty-four human papillary carcinoma tissues were
      included in this study. The expressions of Glut-1- and thyroid-specific genes
      [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor
      and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios
      versus the expression of beta-actin. Pathologic differentiation of papillary
      carcinoma was classified into a relatively well-differentiated group (n = 13) and
      relatively less differentiated group (n = 11). RESULTS: Glut-1 gene expression
      was significantly higher in the less differentiated group (0.66 +/- 0.04) than in
      the well-differentiated group (0.59 +/- 0.07). The expression levels of the NIS,
      PD and TG genes were significantly higher in the well-differentiated group (NIS:
      0.67 +/- 0.20, PD: 0.65 +/- 0.21, TG: 0.74 +/- 0.16) than in the less
      differentiated group (NIS: 0.36 +/- 0.05, PD: 0.49 +/- 0.08, TG: 0.60 +/- 0.11),
      respectively. A significant negative correlation was found between Glut-1 and NIS
      expression, and positive correlations were found between NIS and TG, and between
      NIS and PD. CONCLUSION: The NIS, PD and TG genes were highly expressed in well
      differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed
      in less differentiated thyroid carcinomas. These findings provide a molecular
      rationale for the management of papillary carcinoma, especially in the selection
      of FDG PET or radioiodine whole-body scan and I-131-based therapy.

PMID- 24900149
TI  - Usefulness of Integrated PET/MRI in Head and Neck Cancer: A Preliminary Study.
AB  - PURPOSE: The new modality of an integrated positron emission tomography/magnetic
      resonance imaging (PET/MRI) has recently been introduced but not validated. Our
      objective was to evaluate clinical performance of (18)F-fluoro-2-deoxyglucose
      ((18)F-FDG) PET/MRI in patients with head and neck cancer. METHODS: This
      retrospective study was conducted between January 2013 and February 2013. Ten
      patients (eight men, two women; mean age, 61.4 +/- 13.4 years) with
      histologically proven head and neck tumors were enrolled. Whole-body PET/MRI and
      regional positron emission tomography (PET) with dedicated MRI were sequentially
      obtained. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor
      volume, total lesion glycolysis and contrast enhancement were analyzed. A total
      of ten whole-body positron emission tomography (PET), ten regional positron
      emission tomography (PET), ten dedicated MRI and ten regional PET/gadolinium
      enhanced T1-weighted (Gd)-MRI images were analyzed for initial staging. Two
      nuclear medicine physicians analyzed positron emission tomography (PET) and
      PET/MRI with a consensus. One radiologist analyzed dedicated MRI. The primary
      lesions and number of metastatic lymph nodes analyzed from each image were
      compared. RESULTS: Eight patients were diagnosed with head and neck cancer (one
      tongue cancer, four tonsillar cancers, one nasopharyngeal cancer and two
      hypopharyngeal cancers) by histological diagnosis. Two benign tumors (pleomorphic
      adenoma and Warthin tumor) were diagnosed with surgical operation. Whole-body
      positron emission tomography (PET) and regional positron emission tomography
      (PET) attenuated by MRI showed good image quality for the lesion detection. Whole
      body positron emission tomography (PET) and regional positron emission tomography
      (PET) detected ten primary sites and compensated for a missed lesion on dedicated
      MRI. A discordant number of suspicious lymph node metastases was noted according
      to the different images; 22, 16, 39 and 40 in the whole-body positron emission
      tomography (PET) only, dedicated MR, regional positron emission tomography (PET)
      only and regional PET/Gd-MRI, respectively. There was no distant metastasis based
      on analysis of whole-body positron emission tomography (PET) and whole-body
      PET/Dixon-volume interpolated breathhold examination (VIBE) MRI. Regional PET/Gd
      MRI combined with whole-body PET/MRI modified staging in three patients. Lesions
      of primary tumor and suspicious metastasis were well detected on both value of
      SUVmax and visual analysis. The regional PET/Gd-MRI combined with whole-body
      PET/MRI showed convenient clinical staging performance compared with positron
      emission tomography (PET) and MRI alone. CONCLUSION: In this preliminary study,
      PET attenuated by MRI showed good image quality to detect lesions. And whole-body
      PET/MRI as a single modality was feasible for staging in a clinical setting.
      Whole-body positron emission tomography (PET), regional positron emission
      tomography (PET), dedicated MRI and regional PET/Gd-MRI showed discordant results
      in lesion detection. These discordant results might be synergistic effect for
      accurate staging.

PMID- 24900150
TI  - Differential Diagnosis of Patients with Inconclusive Parkinsonian Features Using
      [(18)F]FP-CIT PET/CT.
AB  - PURPOSE: It is often difficult to differentiate parkinsonism, especially when
      patients show uncertain parkinsonian features. We investigated the usefulness of
      dopamine transporter (DAT) imaging for the differential diagnosis of inconclusive
      parkinsonism using [(18)F]FP-CIT PET. METHODS: Twenty-four patients with
      inconclusive parkinsonian features at initial clinical evaluation and nine
      healthy controls were studied. Patients consisted of three subgroups: nine
      patients whose diagnoses were unclear concerning whether they had idiopathic
      Parkinson's disease or drug-induced parkinsonism ('PD/DIP'), nine patients who
      fulfilled neither the diagnostic criteria of PD nor of essential tremor
      ('PD/ET'), and six patients who were alleged to have either PD or atypical
      parkinsonian syndrome ('PD/APS'). Brain PET images were obtained 120 min after
      injection of 185 MBq [(18)F]FP-CIT. Imaging results were quantified and compared
      with follow-up clinical diagnoses. RESULTS: Overall, 11 of 24 patients
      demonstrated abnormally decreased DAT availability on the PET scans, whereas 13
      were normal. PET results could diagnose PD/DIP and PD/ET patients as having PD in
      six patients, DIP in seven, and ET in five; however, the diagnoses of all six
      PD/APS patients remained inconclusive. Among 15 patients who obtained a final
      follow-up diagnosis, the image-based diagnosis was congruent with the follow-up
      diagnosis in 11 patients. Four unsolved cases had normal DAT availability, but
      clinically progressed to PD during the follow-up period. CONCLUSION: [(18)F]FP
      CIT PET imaging is useful in the differential diagnosis of patients with
      inconclusive parkinsonian features, except in patients who show atypical features
      or who eventually progress to PD.

PMID- 24900151
TI  - Prognostic Value of SUVmax Measured by Fluorine-18 Fluorodeoxyglucose Positron
      Emission Tomography with Computed Tomography in Patients with Gallbladder Cancer.
AB  - OBJECTIVE: The aim of this study is to investigate the prognostic value of F-18
      fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed
      tomography (CT) in gallbladder cancer patients. METHODS: From June 2004 to June
      2010, a total of 50 patients with gallbladder cancer who underwent diagnostic
      staging with F-18 FDG PET/CT following curative or palliative treatments were
      retrospectively evaluated. For the analysis, all patients were classified by age,
      sex, maximum standardized uptake value (SUVmax), lymph node (LN) or distant
      metastasis, serum level of CA19-9 and CEA, type of treatment and American Joint
      Committee on Cancer (AJCC) stage. RESULTS: The median survival for the 50
      patients was 245 days and the median SUVmax in PET/CT was 8.3 (range, 0-19.7).
      Patients with SUVmax < 6 survived significantly longer than patients with SUVmax
      >= 6 (median 405 days vs 203 days, p = 0.0400). On Kaplan-Meier analysis, SUVmax
      (p = 0.0400), stage (p = 0.0001), CA19-9 (p = 0.013), CEA (p = 0.006), LN
      metastasis (p = 0.0001), distant metastasis (p = 0.0020), type of treatment (p =
      0.0001) were significantly associated with overall survival. Multivariate
      analysis study revealed that the patients with lower SUVmax measured from initial
      staging PET/CT (p = 0.0380), no LN metastasis (p = 0.0260), a lower stage (p =
      0.026) and curative treatment (p = 0.0005) had longer survivals. CONCLUSIONS: The
      present study shows that SUVmax on F-18 FDG PET/CT can provide prognostic
      information in patients with gallbladder cancer.

PMID- 24900152
TI  - The Clinical Role of Dual-Time-Point (18)F-FDG PET/CT in Differential Diagnosis
      of the Thyroid Incidentaloma.
AB  - Thyroid incidentalomas are common findings during imaging studies including (18)F
      fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography
      (PET/CT) for cancer evaluation. Although the overall incidence of incidental
      thyroid uptake detected on PET imaging is low, clinical attention should be
      warranted owing to the high incidence of harboring primary thyroid malignancy. We
      retrospectively reviewed 2,368 dual-time-point (18)F-FDG PET/CT cases that were
      undertaken for cancer evaluation from November 2007 to February 2009, to
      determine the clinical impact of dual-time-point imaging in the differential
      diagnosis of thyroid incidentalomas. Focal thyroid uptake was identified in 64
      PET cases and final diagnosis was clarified with cytology/histology in a total of
      27 patients with (18)F-FDG-avid incidental thyroid lesion. The maximum
      standardized uptake value (SUVmax) of the initial image (SUV1) and SUVmax of the
      delayed image (SUV2) were determined, and the retention index (RI) was calculated
      by dividing the difference between SUV2 and SUV1 by SUV1 (i.e., RI = [SUV2 -
      SUV1]/SUV1 * 100). These indices were compared between patient groups that were
      proven to have pathologically benign or malignant thyroid lesions. There was no
      statistically significant difference in SUV1 between benign and malignant
      lesions. SUV2 and RI of the malignant lesions were significantly higher than the
      benign lesions. The areas under the ROC curves showed that SUV2 and RI have the
      ability to discriminate between benign and malignant thyroid lesions. The
      predictability of dual-time-point PET parameters for thyroid malignancy was
      assessed by ROC curve analyses. When SUV2 of 3.9 was used as cut-off threshold,
      malignancy on the pathology could be predicted with a sensitivity of 87.5 % and
      specificity of 75 %. A thyroid lesion that shows RI greater than 12.5 % could be
      expected to be malignant (sensitivity 88.9 %, specificity 66.3 %). All malignant
      lesions showed an increase in SUVmax on the delayed images compared with the
      initial images. But in the group of benign lesions, 37.5 % (6/16) showed a
      decrease or no change in SUVmax. Dual-time-point (18)F-FDG PET/CT, obtaining
      additional images 2 h after injection, seems to be a complementary method for the
      differentiation between malignancy and benignity of incidental thyroid lesions. 

PMID- 24900153
TI  - The Role of (18) F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer
      after Concurrent Chemoradiation Therapy.
AB  - PURPOSE: To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake
      after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect
      residual malignancy. METHODS: F-FDG PET/CT was performed before and after CCRT in
      136 patients with cervical cancer. The maximum and mean standardized uptake
      values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and
      post-treatment. SUVs were correlated with treatment response after CCRT. Final
      treatment response was determined by MRI and further follow-up PET/CT. One
      hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients
      underwent further follow-up PET/CT. Patients were classified into two categories:
      patients with residual tumor or patients without residual tumor (complete
      responder). Pre- and post-treatment serum squamous cell carcinoma antigen (SCC)
      levels were also recorded for comparison. The optimal cutoff value of SUVmax for
      predicting residual cervical tumor was determined using receiver-operating
      characteristic (ROC) analysis. RESULTS: Of 136 patients, 124 showed complete
      response on further follow-up studies and 12 were confirmed to have residual
      tumor. The post-treatment SUVmax and pre-/post-treatment SUVmean of complete
      responders were significantly lower than those of patients with residual tumor:
      2.5 +/- 0.8 and 7.2 +/- 4.2/1.9 +/- 0.7 for complete responders and 5.7 +/- 2.6
      and 12.8 +/- 6.9/3.7 +/- 0.7 for patients with residual tumor (p < 0.05). The pre
      treatment SUVmax and pre-/post-treatment serum SCC levels of the complete
      responders tended to be lower than those of patients with residual tumor, but
      this did not have statistical significance. Using ROC analysis, an optimal cutoff
      SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity,
      positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and
      99 %, respectively (p < 0.001). CONCLUSIONS: Persistent cervical FDG uptake
      in(18)F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor
      or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria
      for cervical cancer in post-CCRT PET/CT might help to detect residual tumor.

PMID- 24900154
TI  - Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients
      with Cholangiocarcinoma.
AB  - OBJECTIVES: Although diffuse splenic (18)F-fluorodeoxyglucose (F-18 FDG) uptake
      exceeding hepatic activity, is considered abnormal, its clinical significance is
      rarely discussed in the literature. The aim of this study was to determine the
      contributing factors causing diffusely increased splenic FDG uptake in patients
      with cholangiocarcinoma. METHODS: From January 2010 to March 2013, 140 patients
      (84 men, 56 women) were enrolled in this study. All patients had been diagnosed
      with cholangiocarcinoma and underwent F-18 FDG positron emission
      tomography/computed tomography (PET/CT) for the pretreatment staging work up.
      Clinical records were reviewed retrospectively. Various hematological parameters,
      C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver
      function tests were conducted within 2 days after the F-18 FDG PET/CT study.
      RESULTS: Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19
      patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP)
      7 days before F-18 FDG PET/CT. The CRP level (p < 0.001) and white blood cell
      count (p = 0.023) were significantly higher in the group of patients with diffuse
      splenic FDG uptake. The hemoglobin (p < 0.001) and the hematocrit (p < 0.001)
      were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic
      enzymes, liver function test results, and tumor markers were not significantly
      different between the patients who did or did not have diffusely increased
      splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake
      exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing
      ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and
      the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR,
      1.211; 95% CI, 1.051-1.871). CONCLUSION: In conclusion, our study demonstrated
      that concurrent inflammation could be associated with diffusely increased splenic
      FDG uptake. We suggest that performing ERCP before F-18 FDG PET/CT could cause
      acute inflammation which may induce splenic FDG activity.

PMID- 24900155
TI  - Can Initial (18)F-FDG PET-CT Imaging Give Information on Metastasis in Patients
      with Primary Renal Cell Carcinoma?
AB  - PURPOSE: The aim of this study was to investigate the relationship between the
      maximum standardized uptake values (SUVmax) of primary renal cancers with and
      without metastatic lesions, if any. We also studied the relationship between the
      size of primary renal cancers and their SUVmax, and tried to find a clinical
      value of (18)F-FDG PET-CT for the initial evaluation of renal cell carcinoma
      (RCC). METHODS: The cases of 23 patients, 16 men and 7 women, who underwent PET
      CT examination before operation were retrospectively reviewed. We measured the
      SUVmax of the primary renal cancers and those of any existing metastatic lesions,
      and the size of the primary renal cancers. We compared the SUVmax of primary RCCs
      with metastases and those without metastases, SUVmax of primary RCC and those of
      metastases, and studied the correlation between the size and SUVmax of primary
      RCCs. RESULTS: The SUVmax of primary RCC of the 16 patients without metastasis
      ranged from 1.1 to 5.6 with a median value of 2.6. Those of the patients with
      metastasis ranged from 2.9 to 7.6 with a median of 5.0. The size of the all 23
      primary renal cancers ranged from 1.7 cm to 13.5 cm, with a median of 4.5 cm, and
      their SUVmax ranged from 1.1 to 7.6, with a median of 2.9. There was a
      statistically significant difference between the SUVmax of the primary RCC with
      metastasis (5.3 +/- 1.7) and those without metastasis (2.9 +/- 1.0). There was a
      moderate positive correlation between the sizes and SUVmax of all 23 primary
      RCCs. However, there was no statistically significant correlation between the
      sizes and SUVmax of primary RCCs with metastatic lesions and the same for RCCs
      without metastasis. The cutoff value of SUVmax for predicting extra-renal lesion
      was 4.4 and that for size was 5.8 cm according to the receiver operating
      characteristic curves. CONCLUSIONS: Those who have primary RCC with high SUVmax
      are suggested to have a likelihood of metastasis. Also, there was a moderate
      trend of increasing value of SUVmax of primary RCC as their size increases.
      Physicians should beware of missing extra-renal lesions elsewhere.

PMID- 24900156
TI  - Primary Benign Intraosseous Meningioma on (18)F-FDG PET/CT Mimicking Malignancy.
AB  - We present a case of primary benign intraosseous meningioma in the sphenoid bone
      mimicking malignancy. A 44-year-old female patient who had a protruding right eye
      and headache came to our hospital. MRI showed a large, destructive,
      heterogeneously well-enhancing soft tissue mass in the right sphenoid bone
      suggesting malignancy. (18)F-FDG PET/CT showed a hypermetabolic mass in the same
      site with an SUVmax of 9.1 The pathological diagnosis by surgery revealed that
      this tumor was a WHO grade I transitional meningioma. This case suggests that
      primary benign intraosseous meningioma may show high (18)F-FDG uptake mimicking a
      malignancy. 

PMID- 24900157
TI  - A Case of Habitual Neck Compression Induced Electroencephalogram Abnormalities:
      Differentiating from Epileptic Seizures Using a Tc-99m HMPAO SPECT.
AB  - Self-induced hypoxia has been reported particularly in adolescents, and it can
      result in neurological injury. Here, we present a case of electroencephalogram
      (EEG) abnormalities induced by habitual neck compression differentiated from
      epileptic seizures by Tc-99m HMPAO SPECT. A 19-year-old male was admitted for
      evaluation of recurrent generalized tonic-clonic seizures. No interictal EEG
      abnormality was detected; however, abnormal slow delta waves were found
      immediately after habitual right neck compression. To differentiate EEG
      abnormalities due to a hemodynamic deficit induced by habitual neck compression
      from an epileptic seizure, Tc-99m HMPAO SPECT was performed immediately after
      right carotid artery compression. Abnormal delta waves were triggered, and
      cerebral hypoperfusion in the right internal carotid artery territory was
      detected on Tc-99m HMPAO SPECT. The slow delta wave detected on the EEG resulted
      from the cerebral hypoperfusion because of the habitual neck compression. 

PMID- 24900158
TI  - Evaluation of Azygous Vein Aneurysm Using Integrated PET/MRI.

PMID- 24900159
TI  - Splenosis Mimicking Relapse of a Neuroendocrine Tumor at Gallium-68-DOTATOC
      PET/CT.

PMID- 24900160
TI  - Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT.

PMID- 24900161
TI  - Solitary Plasmacytoma of the Sternum Mimicking Bone Metastasis in a Patient with
      a History of Breast Cancer Evaluated by F-18-FDG PET/CT.

PMID- 24900162
TI  - Mechanical damage to pollen aids nutrient acquisition in Heliconius butterflies
      (Nymphalidae).
AB  - Neotropical Heliconius and Laparus butterflies actively collect pollen onto the
      proboscis and extract nutrients from it. This study investigates the impact of
      the processing behaviour on the condition of the pollen grains. Pollen samples (n
      = 72) were collected from proboscides of various Heliconius species and Laparus
      doris in surrounding habitats of the Tropical Research Station La Gamba (Costa
      Rica). Examination using a light microscope revealed that pollen loads contained
      74.88 +/- 53.67% of damaged Psychotria pollen, 72.04 +/- 23.4% of damaged
      Psiguria/Gurania pollen, and 21.35 +/- 14.5% of damaged Lantana pollen (numbers
      represent median +/- first quartile). Damaged pollen grains showed deformed
      contours, inhomogeneous and/or leaking contents, or they were empty. Experiments
      with Heliconius and Laparus doris from a natural population in Costa Rica
      demonstrated that 200 min of pollen processing behaviour significantly increased
      the percentage of damaged pollen of Psychotria compared to pollen from anthers (P
      = 0.015, Z = -2.44, Mann-Whitney U-test). Examination of pollen loads from green
      house reared Heliconius butterflies resulted in significantly greater amounts of
      damaged Psiguria pollen after 200 min of processing behaviour compared to pollen
      from flowers (P < 0.001, Z = -4.583, Mann-Whitney U-test). These results indicate
      that pollen processing functions as extra oral digestion whereby pollen grains
      are ruptured to make the content available for ingestion.

PMID- 24900163
TI  - Piloting a Savings-Led Microfinance Intervention with Women Engaging in Sex Work
      in Mongolia: Further Innovation for HIV Risk Reduction.
AB  - This paper describes a pilot study testing the feasibility of an innovative
      savings-led microfinance intervention in increasing the economic empowerment and
      reducing the sexual risk behavior of women engaging in sex work in Mongolia.
      Women's economic vulnerability may increase their risk for HIV by compromising
      their ability to negotiate safer sex with partners and heightening the likelihood
      they will exchange sex for survival. Microfinance has been considered a
      potentially powerful structural HIV prevention strategy with women conducting sex
      work, as diversification of income sources may increase women's capacity to
      negotiate safer transactional sex. With 50% of all reported female HIV cases in
      Mongolia detected among women engaging in sex work, direct prevention
      intervention with women conducting sex work represents an opportunity to prevent
      a potentially rapid increase in HIV infection in urban Mongolia. The piloted
      intervention consisted of a matched savings program in which matched savings
      could be used for business development or vocational education, combined with
      financial literacy and business development training for women engaging in sex
      work. Results of the pilot demonstrate participants' increased confidence in
      their ability to manage finances, greater hope for pursuing vocational goals,
      moderate knowledge gains regarding financial literacy, and an initial transition
      from sex work to alternative income generation for five out of nine participants.
      The pilot findings highlight the potential for such an intervention and the need
      for a clinical trial testing the efficacy of savings-led microfinance programs in
      reducing HIV risk for women engaging in sex work in Mongolia.

PMID- 24900164
TI  - A review of pathologies associated with high T1W signal intensity in the basal
      ganglia on Magnetic Resonance Imaging.
AB  - With several functions and a fundamental influence over cognition and motor
      functions, the basal ganglia are the cohesive centre of the brain. There are
      several conditions which affect the basal ganglia and these have various clinical
      and radiological manifestations. Nevertheless, on magnetic resonance imaging
      there is a limited differential diagnosis for those conditions presenting with T1
      weighted spin echo hyperintensity within the central nervous system in general
      and the basal ganglia in particular. The aim of our review is to explore some of
      these basal ganglia pathologies and provide image illustrations. 

PMID- 24900165
TI  - 2pBAb5. Validation of three-dimensional strain tracking by volumetric ultrasound
      image correlation in a pubovisceral muscle model.
AB  - Little is understood about the biomechanical changes leading to pelvic floor
      disorders such as stress urinary incontinence. In order to measure regional
      biomechanical properties of the pelvic floor muscles in vivo, a three dimensional
      (3D) strain tracking technique employing correlation of volumetric ultrasound
      images has been implemented. In this technique, local 3D displacements are
      determined as a function of applied stress and then converted to strain maps. To
      validate this approach, an in vitro model of the pubovisceral muscle, with a
      hemispherical indenter emulating the downward stress caused by intra-abdominal
      pressure, was constructed. Volumetric B-scan images were recorded as a function
      of indenter displacement while muscle strain was measured independently by a
      sonomicrometry system (Sonometrics). Local strains were computed by ultrasound
      image correlation and compared with sonomicrometry-measured strains to assess
      strain tracking accuracy. Image correlation by maximizing an exponential
      likelihood function was found more reliable than the Pearson correlation
      coefficient. Strain accuracy was dependent on sizes of the subvolumes used for
      image correlation, relative to characteristic speckle length scales of the
      images. Decorrelation of echo signals was mapped as a function of indenter
      displacement and local tissue orientation. Strain measurement accuracy was weakly
      related to local echo decorrelation.

PMID- 24900166
TI  - Interferon-alpha-induced sarcoidosis in a patient being treated for hepatitis C.
AB  - PATIENT: Female, 43 FINAL DIAGNOSIS: - SYMPTOMS: Diarrhea * generalized weakness
      * headache * lightheadedness * nausea * rash * short of breath * vomiting
      MEDICATION: - Clinical Procedure: - Specialty: Pulmonology. OBJECTIVE: Rare
      diseae. BACKGROUND: IFN-alpha-2b in combination with ribavirin is now the
      standard of care for the treatment of hepatitis C. Sarcoidosis is a chronic
      multisystem granulomatous disorder characterized by noncaseating granulomas in
      the involved organs. The pathologic hallmark of sarcoidosis is the presence of
      noncaseating granulomas in the interstitium that typically involve the
      lymphatics. CASE REPORT: A 43-year-old woman presented to our care with 2-week
      history of nausea, vomiting, diarrhea, shortness of breath, migraine headache,
      maculopapular rash, generalized weakness, and lightheadedness. She had been
      treated for hepatitis C with telaprevir, ribavirin, and interferon-alpha-2b for 6
      months. Chest radiograph showed bilateral diffuse prominence of bronchovascular
      markings. CT of the chest revealed bilateral diffuse centrilobular nodules with
      associated intralobular septal thickening, thickening of the central
      peribronchovascular interstitium, nodularity of the major fissures, and
      mediastinal lymphadenopathy. These findings were suspicious for atypical
      pulmonary sarcoidosis, possibly interferon-induced. The pathology of the
      mediastinal lymph node biopsy revealed noncaseating granulomatous inflammation
      consistent with the diagnosis of pulmonary sarcoidosis. Pathology of the skin
      punch biopsy showed giant-cell granulomatous inflammation without necrosis. The
      patient was started on prednisone 40 mg daily with a steroid tapering course for
      8 weeks. CONCLUSIONS: The management of IFN-induced sarcoidosis includes the
      discontinuation of IFN therapy with or without the administration of systemic
      corticosteroids. With the increasing prevalence of HCV in the United States, it
      is likely that more IFN-alpha-induced sarcoidosis will be encountered by
      clinicians.

PMID- 24900168
TI  - Introductory Editorial for ACS Medicinal Chemistry Letters.

PMID- 24900167
TI  - Multimodality Imaging in Congenital Heart Disease: an Update.
AB  - The increasing number of survivors of congenital heart disease (CHD) has been
      paralleled by advancement of imaging modalities used for the ongoing assessment
      of these patients. There has been a large body of literature describing new
      approaches to non-invasive assessment of CHD. We will review new applications of
      well established as well as novel techniques for the management and understanding
      of CHD.

PMID- 24900169
TI  - Synthesis and SAR of Benzisothiazole- and Indolizine-beta-d-glucopyranoside
      Inhibitors of SGLT2.
AB  - A series of benzisothiazole- and indolizine-beta-d-glucopyranoside inhibitors of
      human SGLT2 are described. The synthesis of the C-linked heterocyclic glucosides
      took advantage of a palladium-catalyzed cross-coupling reaction between a glucal
      boronate and the corresponding bromo heterocycle. The compounds have been
      evaluated for their human SGLT2 inhibition potential using cell-based functional
      transporter assays, and their structure-activity relationships have been
      described. Benzisothiazole-C-glucoside 16d was found to be an inhibitor of SGLT2
      with an IC50 of 10 nM. 

PMID- 24900170
TI  - Discovery of MK-3207: A Highly Potent, Orally Bioavailable CGRP Receptor
      Antagonist.
AB  - Incorporation of polar functionality into a series of highly potent calcitonin
      gene-related peptide (CGRP) receptor antagonists was explored in an effort to
      improve pharmacokinetics. This strategy identified piperazinone analogues that
      possessed improved solubility at acidic pH and increased oral bioavailability in
      monkeys. Further optimization led to the discovery of the clinical candidate 2
      [(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo
      1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide (MK
      3207) (4), the most potent orally active CGRP receptor antagonist described to
      date. 

PMID- 24900172
TI  - Porphyrin-apidaecin conjugate as a new broad spectrum antibacterial agent.
AB  - The conjugation of the cationic antimicrobial peptide, apidaecin Ib, to the
      anionic photosensitizer, 5(4'-carboxyphenyl)-10,15,20-triphenylporphyrin (cTPP),
      afforded a new antibacterial agent effective, under light activation, against
      both Gram-positive and Gram-negative bacteria. At low concentrations (1.5-15 MUM)
      the conjugate was able to reduce the survival of Escherichia coli cells by 3-4
      log10, and most notably, it resulted photoactive also against hard-to-treat
      Pseudomonas aeruginosa, although at higher concentration (60 MUM). Under similar
      conditions, the photosensitizer alone was only photoactive against Staphylococcus
      aureus while the unconjugated peptide was inactive against all the bacterial
      strains tested. This study shows the possibility of obtaining new broad-spectrum
      apidaecin-photosensitizer conjugates with potent antibacterial activity. 

PMID- 24900171
TI  - Discovery of the First Potent and Selective Inhibitor of Centromere-Associated
      Protein E: GSK923295.
AB  - Inhibition of mitotic kinesins represents a novel approach for the discovery of a
      new generation of anti-mitotic cancer chemotherapeutics. We report here the
      discovery of the first potent and selective inhibitor of centromere-associated
      protein E (CENP-E) 3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)
      1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1
      methylethyl)oxy]benzamide (GSK923295; 1), starting from a high-throughput
      screening hit, 3-chloro-4-isopropoxybenzoic acid 2. Compound 1 has demonstrated
      broad antitumor activity in vivo and is currently in human clinical trials. 

PMID- 24900174
TI  - Fragment screening by surface plasmon resonance.
AB  - Fragment-based drug discovery is a validated approach for the discovery of drug
      candidates. However, the weak affinity of fragment compounds requires highly
      sensitive biophysical techniques, such as nuclear magnetic resonance (NMR) or X
      ray crystallography, to identify hits. Thus the advantages of screening small
      fragment libraries are partly offset by the high cost of biophysical analyses.
      Here we present a method for biosensor-based fragment screening using surface
      plasmon resonance (SPR). In order to reduce the false positive detection rate we
      present a novel method of data analysis that incorporates multiple referencing
      with ligand efficiency. By implementing all necessary steps for assay design,
      data analysis and interpretation, SPR-based fragment screening has potential to
      eliminate all nonspecific (false positive) binders. Therefore, given the
      advantages of low protein consumption, rapid assay development and kinetic and
      thermodynamic validation of hits, SPR can be considered as a primary screening
      technology for fragment-based drug discovery. 

PMID- 24900173
TI  - Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian
      Target of Rapamycin.
AB  - Phosphoinositide 3-kinase alpha (PI3Kalpha) is a critical regulator of cell
      growth and transformation, and its signaling pathway is the most commonly mutated
      pathway in human cancers. The mammalian target of rapamycin (mTOR), a class IV
      PI3K protein kinase, is also a central regulator of cell growth, and mTOR
      inhibitors are believed to augment the antiproliferative efficacy of PI3K/AKT
      pathway inhibition. 2,4-Difluoro-N-{2-(methyloxy)-5-[4-(4-pyridazinyl)-6
      quinolinyl]-3-pyridinyl}benzenesulfonamide (GSK2126458, 1) has been identified as
      a highly potent, orally bioavailable inhibitor of PI3Kalpha and mTOR with in vivo
      activity in both pharmacodynamic and tumor growth efficacy models. Compound 1 is
      currently being evaluated in human clinical trials for the treatment of cancer. 

PMID- 24900175
TI  - Strategic use of plasma and microsome binding to exploit in vitro clearance in
      early drug discovery.
AB  - Apparent intrinsic clearance (CLia) determined from microsomal stability assays
      is a cornerstone in drug discovery. Categorical bins are routinely applied to
      this end point to facilitate analysis. However, such bins ignore the
      interdependent nature of apparent intrinsic microsome clearance on several ADME
      parameters. Considering CLia as a determinant for both metabolic stability and
      potential dose is more appropriate. In this context with proper accounting for
      nonspecific binding to microsomes and plasma, consideration of compounds with
      higher CLia may be warranted. The underlying benefit is the potential increase in
      the number of hits or chemical diversity for evaluation during the early stages
      of programs. 

PMID- 24900176
TI  - Exploring target-selectivity patterns of molecular scaffolds.
AB  - We investigate the question of whether target-selective molecular scaffolds can
      be identified on the basis of currently available compound activity data.
      Starting from a pool of 17745 public domain compounds with activity annotations
      for 433 human targets, we ultimately identify, through a selectivity
      classification and database-mining approach, 42 molecular scaffolds represented
      by multiple compounds that are highly selective for a particular target over one
      or more others. In many other cases, individual compounds representing unique
      scaffolds are target-selective. Hence, currently available public domain compound
      selectivity data are sparse. However, we also identify selectivity patterns that
      evolve around specific targets and are formed by multiple target-selective
      scaffolds. These scaffolds should provide interesting starting points for further
      chemical exploration. 

PMID- 24900177
TI  - Discovery of an Oral Potent Selective Inhibitor of Hematopoietic Prostaglandin D
      Synthase (HPGDS).
AB  - Hematopoietic prostaglandin D synthase (HPGDS) is primarly expressed in mast
      cells, antigen-presenting cells, and Th-2 cells. HPGDS converts PGH2 into PGD2, a
      mediator thought to play a pivotal role in airway allergy and inflammatory
      processes. In this letter, we report the discovery of an orally potent and
      selective inhibitor of HPGDS that reduces the antigen-induced response in
      allergic sheep. 

PMID- 24900178
TI  - Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine
      Protease Inhibitor.
AB  - Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered
      in our laboratories, is currently undergoing phase III clinical trials. Detailed
      investigations toward a second generation protease inhibitor culminated in the
      discovery of narlaprevir (SCH 900518), 37, with improved potency (~10-fold over
      1), pharmacokinetic profile and physicochemical characteristics, currently in
      phase II human trials. Exploration of synthetic sequence for preparation of 37
      resulted in a route that required no silica gel purification for the entire
      synthesis. 

PMID- 24900179
TI  - Vorinostat-like molecules as structural, stereochemical, and pharmacological
      tools.
AB  - The inhibitory activity of an omega-alkoxy analogue of the HDAC inhibitor,
      Vorinostat (SAHA), against the 11 isoforms of HDAC is described and evaluated
      with regard to structural biology information retrieved through computational
      methods. Preliminary absorption and metabolism studies were performed, which
      positioned this compound as a potential candidate for further preclinical studies
      and delineated measures for improving its pharmacokinetic profile. 

PMID- 24900180
TI  - Discovery of 4,4-Disubstituted Quinazolin-2-ones as T-Type Calcium Channel
      Antagonists.
AB  - A novel series of quinazolinone T-type calcium channel antagonists have been
      prepared and evaluated using in vitro and in vivo assays. Optimization of the
      screening hit 3 by modifications of the 3- and 4-positions of the quinazolinone
      ring afforded potent and selective antagonists that displayed in vivo central
      nervous system efficacy in epilepsy and tremor models, as well as significant
      effects on rat active wake as measured by electrocorticogram. 

PMID- 24900181
TI  - Synthesis and In Vitro Evaluation of Imidazo[1,2-b]pyridazines as Ligands for
      beta-Amyloid Plaques.
AB  - A series of imidazo[1,2-b]pyridazine derivatives were synthesized and evaluated
      for binding to amyloid plaques in vitro using synthetic aggregates of Abeta1-40.
      Binding affinities of these compounds were found to range from 11.0 to >1000 nM,
      depending on the various substitution patterns in the 6-position and 2-position.
      2-(4'-Dimethylaminophenyl)-6-(methylthio)imidazo[1,2-b]pyridazine (4) showed high
      binding affinity (K i = 11.0 nM) and might be useful for the development of novel
      positron emission tomography radiotracers for imaging Abeta plaques. 

PMID- 24900182
TI  - Discovery of WAY-260022, a Potent and Selective Inhibitor of the Norepinephrine
      Transporter.
AB  - The potency and selectivity of a series of 1-{(1S)-2-[amino]-1-[3
      (trifluoromethoxy)phenyl]ethyl}cyclohexanol analogues are described. These
      compounds were prepared to improve in vitro metabolic stability and achieve brain
      penetration. Compound 13 (WAY-260022, NRI-022) was found to be a potent inhibitor
      of norepinephrine reuptake and demonstrated excellent selectivity over the
      serotonin and dopamine transporters. Additionally, 13 exhibited oral efficacy in
      a rat model of thermoregulatory dysfunction. 

PMID- 24900183
TI  - Highly Selective Inhibitors of Class II Microbial Fructose Bis-phosphate
      Aldolases.
AB  - We hereby describe the rationale synthesis and biochemical evaluation of the most
      powerful and selective inhibitors of class II fructose bis-phosphate aldolases so
      far reported. These inhibitors are of potential therapeutic interest, since the
      class II enzyme is present exclusively in microorganisms (among which many
      pathogenic species) and is absent from man, plants, and animals. 

PMID- 24900184
TI  - Photodynamic Activity of Liposomal Photosensitizers via Energy Transfer from
      Antenna Molecules to [60]Fullerene.
AB  - Photodynamic therapy (PDT) is an emerging approach for the treatment of tumor
      diseases that has received growing interest in the past few years. In this study,
      we constructed liposomal photosensitizers (PS) for PDT by shoehorning as light
      harvesting "antenna" molecules and dense [60]fullerene (C60) into lipid membrane
      bilayers. The liposomal PS showed improved photodynamic activity toward human
      cancer cells via the photoenergy transfer from photoactivated antenna molecules
      to C60. 

PMID- 24900185
TI  - Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally
      Bioavailable gamma-Secretase Inhibitor.
AB  - During the course of our research efforts to develop a potent and selective gamma
      secretase inhibitor for the treatment of Alzheimer's disease, we investigated a
      series of carboxamide-substituted sulfonamides. Optimization based on potency,
      Notch/amyloid-beta precursor protein selectivity, and brain efficacy after oral
      dosing led to the discovery of 4 (BMS-708163). Compound 4 is a potent inhibitor
      of gamma-secretase (Abeta40 IC50 = 0.30 nM), demonstrating a 193-fold selectivity
      against Notch. Oral administration of 4 significantly reduced Abeta40 levels for
      sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs. 

PMID- 24900186
TI  - Computational analysis of protein hotspots.
AB  - Mapping protein hotspots and analysis of the binding free energy associated with
      each hotspot can provide critical information for drug design. In the present
      study, we have performed computational analysis for the two known hotspots in
      thermolysin. Our data showed that the free energy double-decoupling method can
      determine the binding free energy of different probe molecules associated with
      the same hotspot or different hotspots with the same probe molecule. The less
      expensive cosolvent mapping method can be used to readily identify known protein
      hotspots without prior knowledge and also provide a good estimate of the binding
      free energy, as compared to the more expensive free energy double-decoupling
      method. Hence, the combination of the cosolvent mapping method to identify
      potential protein hotspots followed by more rigorous calculation of the binding
      free energy associated with each hotspot using the double-decoupling method can
      provide very useful information for drug design. 

PMID- 24900187
TI  - Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist.
AB  - The blockade of aberrant hedgehog (Hh) signaling has shown promise for
      therapeutic intervention in cancer. A cell-based phenotypic high-throughput
      screen was performed, and the lead structure (1) was identified as an inhibitor
      of the Hh pathway via antagonism of the Smoothened receptor (Smo). Structure
      activity relationship studies led to the discovery of a potent and specific
      Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl
      4'-(trifluoromethoxy)biphenyl-3-carboxamide (5m, NVP-LDE225), which is currently
      in clinical development. 

PMID- 24900188
TI  - Identification of novel urease inhibitors by high-throughput virtual and in vitro
      screening.
AB  - Ureases are important in both agriculture and human health. Bacterial ureases are
      directly involved in many farm-field problems and pathological conditions. Here,
      we report a structure-based virtual screening of an in-house compound bank of
      about 6000 molecular entities by computational docking and binding free energy
      calculations followed by in vitro screening. Applied protocol leads to the
      identification of novel urease inhibitors, which can serve as starting points for
      structural optimization. 

PMID- 24900189
TI  - Hydration Site Thermodynamics Explain SARs for Triazolylpurines Analogues Binding
      to the A2A Receptor.
AB  - A series of triazolylpurine analogues show interesting and unintuitive structure
      activity relationships against the A2A adenosine receptor. As the 2-substituted
      aliphatic group is initially increased to methyl and isopropyl, there is a
      decrease in potency; however, extending the substituent to n-butyl and n-pentyl
      results in a significant gain in potency. This trend cannot be readily explained
      by ligand-receptor interactions, steric effects, or differences in ligand
      desolvation. Here, we show that a novel method for characterizing solvent
      thermodynamics in protein binding sites correctly predicts the trend in binding
      affinity for this series based on the differential water displacement patterns.
      In brief, small unfavorable substituents occupy a region in the A2A adenosine
      receptor binding site predicted to contain stable waters, while the longer
      favorable substituents extend to a region that contains several unstable waters.
      The predicted binding energies associated with displacing water within these
      hydration sites correlate well with the experimental activities. 

PMID- 24900190
TI  - Discovery of novel benzoxaborole-based potent antitrypanosomal agents.
AB  - We report the discovery of benzoxaborole antitrypanosomal agents and their
      structure-activity relationships on central linkage groups and different
      substitution patterns in the sulfur-linked series. The compounds showed in vitro
      growth inhibition IC50 values as low as 0.02 MUg/mL and in vivo efficacy in acute
      murine infection models against Tryapnosoma brucei. 

PMID- 24900191
TI  - The discovery of setileuton, a potent and selective 5-lipoxygenase inhibitor.
AB  - The discovery of novel and selective inhibitors of human 5-lipoxygenase (5-LO) is
      described. These compounds are potent, orally bioavailable, and active at
      inhibiting leukotriene biosynthesis in vivo in a dog PK/PD model. A major focus
      of the optimization process was to reduce affinity for the human ether-a-go-go
      gene potassium channel while preserving inhibitory potency on 5-LO. These efforts
      led to the identification of inhibitor (S)-16 (MK-0633, setileuton), a compound
      selected for clinical development for the treatment of respiratory diseases. 

PMID- 24900192
TI  - Discovery of Potent and Selective Urea-Based ROCK Inhibitors and Their Effects on
      Intraocular Pressure in Rats.
AB  - A series of urea-based Rho kinase (ROCK) inhibitors were designed and evaluated.
      The discovered compounds had excellent enzyme and cellular potency, high kinase
      selectivity, high aqueous solubility, good porcine corneal penetration, and
      appropriate DMPK profiles for topical applications as antiglaucoma therapeutics. 

PMID- 24900193
TI  - The Discovery of Pyridone and Pyridazone Heterocycles as gamma-Secretase
      Modulators.
AB  - A series of novel pyridazone and pyridone compounds as gamma-secretase modulators
      were discovered. Starting from the initial lead, structure-activity relationship
      studies were carried out in which an internal hydrogen bond was introduced to
      conformationally fix the side chain, and compounds with improved in vitro Abeta42
      inhibition activity and good Abetatotal/Abeta42 selectivity were quickly
      discovered. Compound 35 displayed very good in vitro activity and excellent
      selectivity with good in vivo efficacy in both CRND8 mouse and nontransgenic rat
      models. This compound displayed a good overall profile in terms of rat
      pharmacokinetics and ancillary profile. No abnormal behavior and side effects
      were observed in all of the studies. 

PMID- 24900194
TI  - Allosteric IGF-1R Inhibitors.
AB  - Targeting allosteric protein sites is a promising approach to interfere
      selectively with cellular signaling cascades. We have discovered a novel class of
      allosteric insulin-like growth factor-I receptor (IGF-1R) inhibitors. 3-Cyano-1H
      indole-7-carboxylic acid {1-[4-(5-cyano-1H-indol-3-yl)butyl]piperidin-4-yl}amide
      (10) was found with nanomolar biochemical, micromolar, cellular IGF-1R activity
      and no relevant interference with cellular insulin receptor signaling up to 30
      MUM. The allosteric binding site was characterized by X-ray crystallographic
      studies, and the structural information was used to explain the unique mode of
      action of this new class of inhibitors. 

PMID- 24900195
TI  - Discovery of Dinaciclib (SCH 727965): A Potent and Selective Inhibitor of Cyclin
      Dependent Kinases.
AB  - Inhibition of cyclin-dependent kinases (CDKs) has emerged as an attractive
      strategy for the development of novel oncology therapeutics. Herein is described
      the utilization of an in vivo screening approach with integrated efficacy and
      tolerability parameters to identify candidate CDK inhibitors with a suitable
      balance of activity and tolerability. This approach has resulted in the
      identification of SCH 727965, a potent and selective CDK inhibitor that is
      currently undergoing clinical evaluation. 

PMID- 24900196
TI  - Cobicistat (GS-9350): A Potent and Selective Inhibitor of Human CYP3A as a Novel
      Pharmacoenhancer.
AB  - Cobicistat (3, GS-9350) is a newly discovered, potent, and selective inhibitor of
      human cytochrome P450 3A (CYP3A) enzymes. In contrast to ritonavir, 3 is devoid
      of anti-HIV activity and is thus more suitable for use in boosting anti-HIV drugs
      without risking selection of potential drug-resistant HIV variants. Compound 3
      shows reduced liability for drug interactions and may have potential improvements
      in tolerability over ritonavir. In addition, 3 has high aqueous solubility and
      can be readily coformulated with other agents. 

PMID- 24900197
TI  - Discovery of a Potent, Injectable Inhibitor of Aurora Kinases Based on the
      Imidazo-[1,2-a]-Pyrazine Core.
AB  - The imidazo-[1,2-a]-pyrazine (1) is a dual inhibitor of Aurora kinases A and B
      with modest cell potency (IC50 = 250 nM) and low solubility (5 MUM). Lead
      optimization guided by the binding mode led to the acyclic amino alcohol 12k (SCH
      1473759), which is a picomolar inhibitor of Aurora kinases (TdF K d Aur A = 0.02
      nM and Aur B = 0.03 nM) with improved cell potency (phos-HH3 inhibition IC50 = 25
      nM) and intrinsic aqueous solubility (11.4 mM). It also demonstrated efficacy and
      target engagement in human tumor xenograft mouse models. 

PMID- 24900198
TI  - Metabolism-guided design of short-acting calcium-sensing receptor antagonists.
AB  - As part of a strategy to deliver short-acting calcium-sensing receptor (CaSR)
      antagonists, the metabolically labile thiomethyl functionality was incorporated
      into the zwitterionic amino alcohol derivative 3 with the hope of increasing
      human clearance through oxidative metabolism, while delivering a
      pharmacologically inactive sulfoxide metabolite. The effort led to the
      identification of thioanisoles 22 and 23 as potent and orally active CaSR
      antagonists with a rapid onset of action and short pharmacokinetic half-lives,
      which led to a rapid and transient stimulation of parathyroid hormone in a dose
      dependent fashion following oral administration to rats. On the basis of the
      balance between target pharmacology, safety, and human disposition profiles, 22
      and 23 were advanced as clinical candidates for the treatment of osteoporosis. 

PMID- 24900199
TI  - Synthesis of a (68)ga-labeled peptoid-Peptide hybrid for imaging of neurotensin
      receptor expression in vivo.
AB  - The neurotensin receptor subtype 1 (NTS1) represents an attractive molecular
      target for imaging various tumors. Positron emission tomography (PET) gained
      widespread importance due to its sensitivity. We combined the design of a
      metabolically stable neurotensin analogue with a (68)Ga-radiolabeling approach.
      The (68)Ga-labeled peptoid-peptide hybrid [(68)Ga]3 revealed high stability,
      specific tumor uptake (0.7%ID/g, 65 min p.i.), and advantageous biokinetics in
      vivo using HT29 tumor-bearing nude mice. Because of the ability to internalize
      into NTS1-expressing tumor cells, [(68)Ga]3 proved to be highly suitable for a
      reliable and practical visualization of NTS1-expressing tumors in vivo by small
      animal PET. 

PMID- 24900200
TI  - Optimization of an albumin-binding prodrug of Doxorubicin that is cleaved by
      prostate-specific antigen.
AB  - We have developed a novel albumin-binding prodrug of doxorubicin that
      incorporates p-aminobenzyloxycarbonyl (PABC) as a 1,6 self-immolative spacer in
      addition to the heptapeptide, Arg-Ser-Ser-Tyr-Tyr-Ser-Leu, as a substrate for the
      prostate-specific antigen (PSA) that is overexpressed in prostate carcinoma and
      represents a molecular target for selectively releasing an anticancer agent from
      a prodrug formulation. The prodrug exhibited good water solubility and was bound
      rapidly to the cysteine-34 position of human serum albumin. Incubation studies
      with PSA demonstrated that the albumin-bound form of the prodrug was cleaved
      rapidly at the P1-P1' scissile bond, releasing H-Ser-Leu-PABC-DOXO, which was
      further degraded to release doxorubicin as a final cleavage product within a few
      hours in prostate tumor tissue homogenates as well as in PSA-positive LNCaP LN
      cell lysates. Moreover, our prodrug exhibited antiproliferative activity in a low
      micromolar range against a PSA-expressing prostate cancer cell line (LNCaP). 

PMID- 24900201
TI  - Efficient radiosynthesis of 2-[(18)f]fluoroadenosine: a new route to 2
      [(18)f]fluoropurine nucleosides.
AB  - An efficient method to incorporate the fluorine-18 radionuclide in 2-nitropurine
      based nucleosides was developed. The nucleophilic radiofluorination of the
      labeling precursor with [(18)F]KF under aminopolyether-mediated conditions
      (Kryptofix 2.2.2/K2CO3) followed by deprotection was straightforward and, after
      formulation, gave 2-[(18)F]fluoroadenosine, ready for injection with a
      radiochemical yield of 45 +/- 5%, a radiochemical purity of >98%, and a specific
      radioactivity up to 148 GBq/MUmol. A micropositron emission tomography imaging
      and biodistribution study on rodents was reported. 

PMID- 24900202
TI  - Novel N-Substituted Benzimidazolones as Potent, Selective, CNS-Penetrant, and
      Orally Active M1 mAChR Agonists.
AB  - Virtual screening of the corporate compound collection yielded compound 1 as a
      subtype selective muscarinic M1 receptor agonist hit. Initial optimization of the
      N-capping group of the central piperidine ring resulted in compounds 2 and 3 with
      significantly improved potency and selectivity. Subsequent optimization of
      substituents on the phenyl ring of the benzimidazolone moiety led to the
      discovery of novel muscarinic M1 receptor agonists 4 and 5 with excellent
      potency, general and subtype selectivity, and pharmacokinetic (PK) properties
      including good central nervous system (CNS) penetration and oral bioavailability.
      Compound 5 showed robust in vivo activities in animal models of cognition
      enhancement. The combination of high potency, excellent selectivity, and good PK
      properties makes compounds 4 and 5 valuable tool compounds for investigating and
      validating potential therapeutic benefits resulting from selective M1 activation.

PMID- 24900203
TI  - Development of Fluorescent Ligands for the Human 5-HT1A Receptor.
AB  - In this work, we report the design and synthesis of a set of fluorescent probes
      targeting the human 5-HT1A receptor (h5-HT1AR). Among the synthesized compounds,
      derivative 4 deserves special attention as being a high-affinity ligand (K i = 2
      nM) with good fluorescent properties (I em > 1000 au and a fluorescence quantum
      yield, Phif, of 0.26), which enables direct observation of the h5-HT1AR in cells.
      Thus, it represents the first efficacious fluorescent probe for the specific
      labeling of h5-HT1AR in cells. Our results provide the basis for the introduction
      of a variety of tags in scaffolds of G protein-coupled receptor (GPCR) ligands
      that enable visualization, covalent binding, or affinity pull-down of receptors.
      These strategies should contribute to the optimization of the therapeutic
      exploitation of known or new members of the GPCR superfamily by providing
      valuable information about their location or level of expression. 

PMID- 24900204
TI  - Carbamylation of N-terminal proline.
AB  - Protein carbamylation is of great concern both in vivo and in vitro. Here, we
      report the first structural characterization of a protein carbamylated at the N
      terminal proline. The unexpected carbamylation of the alpha-amino group of the
      least reactive codified amino acid has been detected in high-resolution electron
      density maps of a new crystal form of the HIV-1 protease/saquinavir complex. The
      carbamyl group is found coplanar to the proline ring with a trans conformation.
      The reaction of N-terminal with cyanate ion derived from the chaotropic agent
      urea was confirmed by mass spectra analysis on protease single crystals.
      Implications of carbamylation process in vitro and in vivo are discussed. 

PMID- 24900205
TI  - Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti
      Drug-Resistant Bacteria.
AB  - Muraymycin analogues with a lipophilic substituent were synthesized using an Ugi
      four-component assemblage. This approach provides ready access to a range of
      analogues simply by altering the aldehyde component. The impact of the lipophilic
      substituent on the antibacterial activity was very large, and analogues 7b-e and
      8b-e exhibited good activity against a range of Gram-positive bacterial pathogens
      including methicillin-resistant Staphylococcus aureus and vancomycin-resistant
      Enterococcus faecium. This study also showed that the accessory urea-dipeptide
      motif contributes to MraY inhibitory and antibacterial activity. The knowledge
      obtained from our structure-activity relationship study of muraymycins provides
      further direction toward the design of potent MraY inhibitors. This study has set
      the stage for the generation of novel antibacterial "lead" compounds based on
      muraymycins. 

PMID- 24900206
TI  - Quinolizidinone carboxylic acids as CNS penetrant, selective m1 allosteric
      muscarinic receptor modulators.
AB  - Positive allosteric modulation of the M1 muscarinic receptor represents an
      approach to treat the cognitive decline in patients with Alzheimer's disease.
      Replacement of a quinolone ring system in a quinolone carboxylic acid series of
      M1 modulators with a quinolizidinone bearing a basic amine linkage led to a
      series of compounds with higher free fraction, enhanced CNS exposure, and
      improved efficacy in rodent in vivo models of cognition. 

PMID- 24900207
TI  - KSRP/FUBP2 Is a Binding Protein of GO-Y086, a Cytotoxic Curcumin Analogue.
AB  - Bis(arylmethylidene)acetone derivatives are an important class of curcumin
      analogues that exhibit various biological and pharmacological activities. We
      herein report that GO-Y086, a biotinylated bis(arylmethylidene)acetone, inhibits
      cancer cell growth. We also show that GO-Y086 specifically interacts with the
      nuclear protein KSRP/FUBP2 by covalent modification. GO-Y086 markedly suppresses
      the expression of the c-Myc protein, which plays an important role in cellular
      proliferation and whose expression is regulated by KSRP/FUBP2. 

PMID- 24900208
TI  - Expanded Utility of the beta-Glucuronide Linker: ADCs That Deliver Phenolic
      Cytotoxic Agents.
AB  - The beta-glucuronide linker has been used for antibody-drug conjugates (ADCs) to
      deliver amine-containing cytotoxic agents. The linker is stable in circulation,
      hydrophilic and provides ADCs that are highly active in vitro and in vivo. To
      extend the utility of the beta-glucuronide linker toward phenol-containing drugs,
      an N,N'-dimethylethylene diamine self-immolative spacer was incorporated with the
      linker for release of the potent cytotoxic phenol psymberin A. Exposure of the
      drug-linker to beta-glucuronidase resulted in facile drug release. The
      corresponding ADCs were active and immunologically selective against CD30
      positive L540cy and CD70-positive Caki-1 cell lines. 

PMID- 24900209
TI  - Synthesis and Biochemical Testing of 3-(Carboxyphenylethyl)imidazo[2,1
      f][1,2,4]triazines as Inhibitors of AMP Deaminase.
AB  - C-Ribosyl imidazo[2,1-f][1,2,4]triazines and 3-[2-(3-carboxyphenyl)ethyl]-3,6,7,8
      tetrahydroimidazo[4,5-d][1,3]diazepin-8-ols represent two classes of known AMP
      deaminase inhibitors. A combination of the aglycone from the former class with
      the ribose phosphate mimic from the latter led to the 3-[2-(3
      carboxyphenyl)ethyl]imidazo[2,1-f][1,2,4]triazines, which represent a new class
      of AMP deaminase inhibitors. The best compound, 3-[2-(3-carboxy-5,6,7,8
      tetrahydronaphthyl)ethyl]imidazo[2,1-f][1,2,4]triazine (8), was a good inhibitor
      of all three human AMPD recombinant isozymes (AMPD1, AMPD2, and AMPD3; IC50 = 0.9
      5.7 MUM) but a poor inhibitor of the plant recombinant enzyme (Arabidopsis FAC1;
      IC50 = 200 MUM). 

PMID- 24900210
TI  - Discovery of TAK-875: A Potent, Selective, and Orally Bioavailable GPR40 Agonist.
AB  - GPR40, one of the G protein-coupled receptors predominantly expressed in
      pancreatic beta-cells, mediates enhancement of glucose-stimulated insulin
      secretion by free fatty acids. A potent and selective GPR40 agonist is theorized
      to be a safe and effective antidiabetic drug with little or no risk of
      hypoglycemia. Cyclization of the phenylpropanoic acid moiety of lead compound 1
      produced fused phenylalkanoic acids with favorable in vitro agonist activities
      and pharmacokinetic profiles. Further optimization led to the discovery of
      dihydrobenzofuran derivative 9a ([(3S)-6-({2',6'-dimethyl-4'-[3
      (methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3
      yl]acetic acid hemi-hydrate, TAK-875) as a potent, selective, and orally
      bioavailable GPR40 agonist, with a pharmacokinetic profile enabling long-acting
      drug efficacy. Compound 9a showed potent plasma glucose-lowering action and
      insulinotropic action during an oral glucose tolerance test in female Wistar
      fatty rats with impaired glucose tolerance. Compound 9a is currently in clinical
      trials for the treatment of type 2 diabetes mellitus. 

PMID- 24900211
TI  - Labeled Ligand Displacement: Extending NMR-Based Screening of Protein Targets.
AB  - NMR spectroscopy has enjoyed widespread success as a method for screening protein
      targets, especially in the area of fragment-based drug discovery. However,
      current methods for NMR-based screening all suffer certain limitations. Two
      dimensional methods like "SAR by NMR" require isotopically labeled protein and
      are limited to proteins less than about 50 kDa. For one-dimensional, ligand-based
      methods, results can be confounded by nonspecific compound binding, resonance
      overlap, or the need for a special NMR probe. We present here a ligand-based
      method that relies on the exchange broadening observed for a (13)C-labeled
      molecule upon binding to a protein target (labeled ligand displacement). This
      method can be used to screen both individual compounds and mixtures and is free
      of the artifacts inherent in other ligand-based methods. 

PMID- 24900212
TI  - Targeting the c-Kit Promoter G-quadruplexes with 6-Substituted
      Indenoisoquinolines.
AB  - Herein, we demonstrate the design, synthesis, biophysical properties, and
      preliminary biological evaluation of 6-substituted indenoisoquinolines as a new
      class of G-quadruplex stabilizing small molecule ligands. We have synthesized 6
      substituted indenoisoquinolines 1a-e in two steps from commercially available
      starting materials with excellent yields. The G-quadruplex stabilization
      potential of indenoisoquinolines 1a-e was evaluated by fluorescence resonance
      energy transfer-melting analysis, which showed that indenoisoquinolines show a
      high level of stabilization of various G-quadruplex DNA structures.
      Indenoisoquinolines demonstrated potent inhibition of cell growth in the GIST882
      patient-derived gastrointestinal stromal tumor cell line, accompanied by
      inhibition of both c-Kit transcription and KIT oncoprotein levels. 

PMID- 24900213
TI  - Novel 3-Oxazolidinedione-6-aryl-pyridinones as Potent, Selective, and Orally
      Active EP3 Receptor Antagonists.
AB  - High-throughput screening and subsequent optimization led to the discovery of
      novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent
      and selective EP3 antagonists with excellent pharmacokinetic properties. Compound
      2 was orally active and showed robust in vivo activities in overactive bladder
      models. To address potential bioactivation liabilities of compound 2, further
      optimization resulted in compounds 9 and 10, which maintained excellent potency,
      selectivity, and pharmacokinetic properties and showed no bioactivation liability
      in glutathione trapping studies. These highly potent, selective, and orally
      active EP3 antagonists are excellent tool compounds for investigating and
      validating potential therapeutic benefits from selectively inhibiting the EP3
      receptor. 

PMID- 24900214
TI  - Fluorinated Benzofuran Derivatives for PET Imaging of beta-Amyloid Plaques in
      Alzheimer's Disease Brains.
AB  - A series of fluorinated benzofuran derivatives as potential tracers for positron
      emission tomography (PET) targeting beta-amyloid plaques in the brains of
      patients with Alzheimer's disease (AD) were synthesized and evaluated. The
      derivatives were produced using an intramolecular Wittig reaction. In experiments
      in vitro, all displayed high affinity for Abeta(1-42) aggregates with K i values
      in the nanomolar range. Radiofluorinated 17, [(18)F]17, in particular labeled
      beta-amyloid plaques in sections of Tg2576 mouse brain and displayed high uptake
      (5.66% ID/g) at 10 min postinjection, sufficient for PET imaging. In addition, in
      vivo beta-amyloid plaque labeling can be clearly demonstrated with [(18)F]17 in
      Tg2576 mice. In conclusion, [(18)F]17 may be useful for detecting beta-amyloid
      plaques in patients with AD. 

PMID- 24900215
TI  - [Au2(phen(2Me))2(MU-O)2](PF6)2, a Novel Dinuclear Gold(III) Complex Showing
      Excellent Antiproliferative Properties.
AB  - A novel dioxo-bridged dinuclear gold(III) complex with two 2,9
      dimethylphenanthroline ligands was synthesized and thoroughly characterized. Its
      crystal structure was solved, and its solution behavior assessed. Remarkably,
      this compound revealed excellent antiproliferative properties in vitro against a
      wide panel of 36 cancer cell lines, combining a high cytotoxic potency to
      pronounced tumor selectivity. Very likely, these properties arise from an
      innovative mode of action (possibly involving histone deacetylase inhibition), as
      suggested by COMPARE analysis. In turn, electrospray ionization-mass spectrometry
      studies provided valuable insight into its molecular mechanisms of activation and
      of interaction with protein targets. Gold(III) reduction, dioxo bridge
      disruption, coordinative gold(I) binding to the protein, and concomitant release
      of the phenanthroline ligand were proposed to occur upon interaction with
      superoxide dismutase, used here as a model protein. Because of the reported
      results, this new gold(III) compound qualifies itself as an optimal candidate for
      further pharmacological testing. 

PMID- 24900216
TI  - Novel and Potent 5-Piperazinyl Methyl-N 1-aryl Sulfonyl Indole Derivatives as 5
      HT6 Receptor Ligands.
AB  - The exclusive distribution of 5-HT6 receptors in the brain regions associated
      with learning and memory makes it an ideal target for cognitive disorders. A
      novel series of 5-piperazinyl methyl-N 1-aryl sulfonyl indoles were designed and
      synthesized as 5-HT6R ligands. Most of the synthesized compounds are potent when
      tested by in vitro radioligand binding assay. The lead compound from the series
      does not have the CYP liabilities and is active in an animal model of cognition. 

PMID- 24900217
TI  - Structure-Activity Study of Dihydrocinnamic Acids and Discovery of the Potent
      FFA1 (GPR40) Agonist TUG-469.
AB  - The free fatty acid 1 receptor (FFA1 or GPR40), which is highly expressed on
      pancreatic beta-cells and amplifies glucose-stimulated insulin secretion, has
      emerged as an attractive target for the treatment of type 2 diabetes. Several
      FFA1 agonists containing the para-substituted dihydrocinnamic acid moiety are
      known. We here present a structure-activity relationship study of this compound
      family suggesting that the central methyleneoxy linker is preferable for the
      smaller compounds, whereas the central methyleneamine linker gives higher potency
      to the larger compounds. The study resulted in the discovery of the potent and
      selective full FFA1 agonist TUG-469 (29). 

PMID- 24900218
TI  - Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of
      GlyT1.
AB  - Amalgamation of the structure-activity relationship of two series of GlyT1
      inhibitors developed at Merck led to the discovery of a clinical candidate,
      compound 16 (DCCCyB), which demonstrated excellent in vivo occupancy of GlyT1
      transporters in rhesus monkey as determined by displacement of a PET tracer
      ligand. 

PMID- 24900219
TI  - Discovery of Novel Benzo[a]phenoxazine SSJ-183 as a Drug Candidate for Malaria.
AB  - Malaria is a serious infectious disease caused by protozoan parasites in tropical
      and subtropical regions. Even inhabitants of temperate zones are exposed to the
      danger of malaria infection because of travel and global warming. Novel,
      effective, safe, and inexpensive drugs are required to treat malaria and
      contribute to the global goal of eradication. A search for new antimalarial
      agents has been performed by the synthesis of new benzo[a]phenoxazines, followed
      by biological evaluations. The derivative SSJ-183 (5), having a 4-aminopyridine
      group, showed an IC50 value against Plasmodium falciparum of 7.6 nM and a
      selectivity index of >7300. Cure was achieved by three oral doses of 5 at 100
      mg/kg to mice infected with the Plasmodium berghei ANKA strain. The safety of 5
      was supported by acute toxicity testing in mice with single doses up to 2000
      mg/kg po, chromosome aberration test, in vitro as well as in vivo micronucleus
      tests, and phototoxicity studies in mice. Thus, 5 is a promising candidate as a
      new antimalarial agent. 

PMID- 24900220
TI  - Identification of a New Series of STAT3 Inhibitors by Virtual Screening.
AB  - The signal transducer and activator of transcription 3 (STAT3) is considered to
      be an attractive therapeutic target for oncology drug development. We identified
      a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a
      novel STAT3 dimerization inhibitor by a virtual screen using a customized version
      of the DOCK4 program with the crystal structure of STAT3. In addition, we used in
      vitro cell-based assays such as the luciferase reporter gene assay and the
      fluorescence resonance energy transfer-based STAT3 dimerization assay. STX-0119
      selectively abrogated the DNA binding activity of STAT3 and suppressed the
      expression of STAT3-regulated oncoproteins such as c-myc and survivin in cancer
      cells. In contrast, a truncated inactive analogue, STX-0872, did not exhibit
      those activities. Oral administration of STX-0119 effectively abrogated the
      growth of human lymphoma cells in a SCC-3 subcutaneous xenograft model without
      visible toxicity. Structure-activity relationships of STX-0119 derivatives were
      investigated using the docking model of the STAT3-SH2 domain/STX-0119. 

PMID- 24900221
TI  - Ranking ligand affinity for the DNA minor groove by experiment and simulation.
AB  - The structural and thermodynamic basis for the strength and selectivity of the
      interactions of minor groove binders (MGBs) with DNA is not fully understood. In
      2003, we reported the first example of a thiazole-containing MGB that bound in a
      phase-shifted pattern that spanned six base pairs rather than the usual four (for
      tricyclic distamycin-like compounds). Since then, using DNA footprinting, NMR
      spectroscopy, isothermal titration calorimetry, and molecular dynamics, we have
      established that the flanking bases around the central four being read by the
      ligand have subtle effects on recognition. We have investigated the effect of
      these flanking sequences on binding and the reasons for the differences and
      established a computational method to rank ligand affinity against varying DNA
      sequences. 

PMID- 24900222
TI  - Cytotoxic Profile and Peculiar Reactivity with Biomolecules of a Novel "Rule
      Breaker" Iodidoplatinum(II) Complex.
AB  - Novel and surprising biological properties were disclosed for the platinum(II)
      complex cis-diiodidodiisopropylamineplatinum(II). Remarkably, this new
      platinum(II) complex manifests pronounced antiproliferative properties in vitro,
      in some cases superior to those of cisplatin. A peculiar reactivity with the
      model protein cytochrome c was indeed highlighted based on the loss of amine
      ligands and retention of iodides. 

PMID- 24900223
TI  - Structure-Activity Studies on Antiproliferative Factor (APF) Glycooctapeptide
      Derivatives.
AB  - Antiproliferative factor (APF), a sialylated glycopeptide secreted by explanted
      bladder epithelial cells from interstitial cystitis/painful bladder syndrome
      (IC/PBS) patients, and its unsialylated analogue (as-APF) significantly decrease
      proliferation of bladder epithelial cells and/or certain carcinoma cell lines in
      vitro. We recently reported a structure-activity relationship profile for the
      peptide portion of as-APF and revealed that truncation of the C-terminal alanine
      did not significantly affect antiproliferative activity. To better understand the
      structural basis for the maintenance of activity of this truncated eight amino
      acid as-APF (as-APF8), we synthesized several amino acid-substituted derivatives
      and studied their ability to inhibit bladder epithelial cell proliferation in
      vitro as well as their solution conformations by CD and NMR spectroscopy. While
      single amino acid changes to as-APF8 often strongly reduced activity, full
      potency was retained when the trivaline tail was replaced with three alanines.
      The Ala(6-8) derivative 9 is the simplest, fully potent APF analogue synthesized
      to date. 

PMID- 24900224
TI  - Discovery of Oxazolobenzimidazoles as Positive Allosteric Modulators for the
      mGluR2 Receptor.
AB  - Novel oxazolobenzimidazoles are described as potent and selective positive
      allosteric modulators of the metabotropic glutamate receptor 2. The discovery of
      this class and optimization of its physical and pharmacokinetic properties led to
      the identification of potent and orally bioavailable compounds (20 and 21) as
      advanced leads. Compound 20 (TBPCOB) was shown to have robust activity in a PCP
      induced hyperlocomotion model in rat, an assay responsive to clinical
      antipsychotic treatments for schizophrenia. 

PMID- 24900225
TI  - Antiproliferative and differentiating activities of a novel series of histone
      deacetylase inhibitors.
AB  - Histone deacetylases are promising molecular targets for the development of
      antitumor agents. A novel series of histone deacetylase inhibitors of the
      hydroxamic acid type were synthesized for structure-activity studies. Thirteen
      tricyclic dibenzo-diazepine, -oxazepine, and -thiazepine analogues were studied
      and shown to induce variable degrees of histone H3/H4 and tubulin acetylation in
      a cellular model of myeloid leukemia sensitive to all-trans retinoic acid (ATRA).
      Multiparametric correlations between acetylation of the three substrates, tumor
      cell growth inhibition, and ATRA-dependent cytodifferentiation were performed,
      providing information on the chemical functionalities governing these activities.
      For two analogues, antitumor activity in the animal was demonstrated. 

PMID- 24900226
TI  - From taxuspine x to structurally simplified taxanes with remarkable p
      glycoprotein inhibitory activity.
AB  - Three simplified "non-natural" natural taxanes, related to taxuspine X, were
      synthetized and assayed as P-glycoprotein (P-gp) inhibitors. One of them (6)
      proved to be a very efficient P-gp inhibitor with an IC50 = 7.2 * 10(-6) M. In
      addition, to rationalize biological data, a pharmacophoric model was built
      through a ligand-based approach. This model represents the first example of a
      pharmacophore, which describes interactions of taxanes with P-gp. 

PMID- 24900227
TI  - Exploring alpha7-Nicotinic Receptor Ligand Diversity by Scaffold Enumeration from
      the Chemical Universe Database GDB.
AB  - Virtual analogues (1167860 compounds) of the nicotinic alpha7-receptor (alpha7
      nAChR) ligands PNU-282,987 and SSR180711 were generated from the chemical
      universe database GDB-11 by extracting all aliphatic diamine analogues of the
      aminoquinuclidine and 1,4-diazabicyclo[3.2.2]nonane scaffolds of these ligands
      and converting them to the corresponding aryl amides using five different
      aromatic acyl groups. The library was ranked by docking to the nicotinic binding
      site of the acetylcholine binding protein (AChBP, 1UW6.pdb) using Autodock and
      Glide. Thirty-eight ligands derived from the best docking hits were synthesized
      and tested for modulation of the acetylcholine signal at the human alpha7 nAChR
      receptor expressed in Xenopus oocytes, leading to competitive and noncompetitive
      antagonists with IC50 = 5-7 MUM. These experiments demonstrate the first example
      of using GDB in a fragment-based approach by diversifying the scaffold of known
      drugs. 

PMID- 24900228
TI  - DNA Sequence Preference and Adduct Orientation of Pyrrolo[2,1
      c][1,4]benzodiazepine Antitumor Agents.
AB  - The pyrrolobenzodiazepines (PBDs) are covalent DNA minor-groove binding agents
      with a reported preference for binding to 5'-Pu-G-Pu sequences with their A rings
      oriented toward the 3'-end of the covalently modified DNA strand. Using HPLC/MS
      methodology and a range of designed hairpin-forming 17-mer oligonucleotides, the
      kinetics of reaction of a bis-pyrrole PBD conjugate (GWL-78, 2) has been
      evaluated with eight isomeric oligonucleotides, each containing a single PBD
      binding site in one of two locations. The PBD-binding base pair triplets were
      designed to include every possible combination of A and T bases adjacent to the
      covalently reacting guanine. Contrary to expectations, 2 reacted most rapidly
      with TGT and TGA sequences, and adducts were observed to form in both the 3'- and
      the 5'-directions. Molecular modeling studies revealed that for 3'-oriented
      adducts, this preference could be explained by formation of a hydrogen bond
      between the N10-H of the PBD and the oxygen of the C2-carbonyl of a thymine base
      on the 3'-side of the covalently bound guanine. For 5'-adducts, an analogous PBD
      N10-H hydrogen bond may form instead to the N3 of an equivalent adenine on the
      opposite strand. 

PMID- 24900229
TI  - Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery.
AB  - Fragment screening of phosphoinositide-dependent kinase-1 (PDK1) in a biochemical
      kinase assay afforded hits that were characterized and prioritized based on
      ligand efficiency and binding interactions with PDK1 as determined by NMR.
      Subsequent crystallography and follow-up screening led to the discovery of
      aminoindazole 19, a potent leadlike PDK1 inhibitor with high ligand efficiency.
      Well-defined structure-activity relationships and protein crystallography provide
      a basis for further elaboration and optimization of 19 as a PDK1 inhibitor. 

PMID- 24900230
TI  - Novel Benzofurans with (99m)Tc Complexes as Probes for Imaging Cerebral beta
      Amyloid Plaques.
AB  - Two novel benzofuran derivatives coupled with (99m)Tc complexes were tested as
      probes for imaging cerebral beta-amyloid plaques using single photon emission
      tomography. Although both derivatives bound to Abeta(1-42) aggregates, (99m)Tc
      BAT-BF showed higher affinity than (99m)Tc-MAMA-BF. In sections of brain tissue
      from an animal model of AD, (99m)Tc-BAT-BF clearly labeled beta-amyloid plaques.
      In biodistribution experiments using normal mice, (99m)Tc-BAT-BF displayed high
      uptake soon after its injection and washed out from the brain rapidly, a highly
      desirable feature for an imaging agent. (99m)Tc-BAT-BF may be a potential probe
      for imaging beta-amyloid plaques in Alzheimer's brains. 

PMID- 24900231
TI  - Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3
      Signaling Pathway.
AB  - Inhibition of the signal transducer and activator of transcription 3 (STAT3)
      signaling pathway has been considered a novel therapeutic strategy to treat human
      cancers with constitutively active STAT3. In this study, we report the
      identification of niclosamide, an FDA-approved anthelmintic drug, as a new small
      molecule inhibitor of the STAT3 signaling pathway. This compound potently
      inhibited the activation and transcriptional function of STAT3 and consequently
      induced cell growth inhibition, apoptosis, and cell cycle arrest of cancer cells
      with constitutively active STAT3. Our study provides a new promising lead
      compound with a salicylic amide scaffold for the development of STAT3 pathway
      inhibitors as novel molecularly targeted anticancer drugs. 

PMID- 24900232
TI  - Pyridine Carboxamides: Potent Palm Site Inhibitors of HCV NS5B Polymerase.
AB  - Pyridine carboxamide-based inhibitors of the hepatitis C virus (HCV) NS5B
      polymerase were diversified and optimized to a variety of topologically related
      scaffolds. In particular, the 2-methyl nicotinic acid scaffold was developed into
      inhibitors with improved biochemical (IC50-GT1b = 0.014 MUM) and cell-based HCV
      replicon potency (EC50-GT1b = 0.7 MUM). Biophysical and biochemical
      characterization identified this novel series of compounds as palm site binders
      to HCV polymerase. 

PMID- 24900233
TI  - Discovery of omecamtiv mecarbil the first, selective, small molecule activator of
      cardiac Myosin.
AB  - We report the design, synthesis, and optimization of the first, selective
      activators of cardiac myosin. Starting with a poorly soluble, nitro-aromatic hit
      compound (1), potent, selective, and soluble myosin activators were designed
      culminating in the discovery of omecamtiv mecarbil (24). Compound 24 is currently
      in clinical trials for the treatment of systolic heart failure. 

PMID- 24900234
TI  - A Potent and Selective AMPK Activator That Inhibits de Novo Lipogenesis.
AB  - AMP-activated protein kinase (AMPK) is a heterotrimeric kinase that regulates
      cellular energy metabolism by affecting energy-consuming pathways such as de novo
      lipid biosynthesis and glucose production as well as energy-producing pathways
      such as lipid oxidation and glucose uptake. Accordingly, compounds that activate
      AMPK represent potential drug candidates for the treatment of hyperlipidemia and
      type 2 diabetes. Screening of a proprietary library of AMP mimetics identified
      the phosphonic acid 2 that bears little structural resemblance to AMP but is
      capable of activating AMPK with high potency (EC50 = 6 nM vs AMP EC50 = 6 MUM)
      and specificity. Phosphonate prodrugs of 2 inhibited de novo lipogenesis in
      cellular and animal models of hyperlipidemia. 

PMID- 24900235
TI  - Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5
      Antagonist with Potent Anti-HIV-1 Activity.
AB  - To identify a CCR5 antagonist as an HIV-1 entry inhibitor, we designed a novel
      series of indane derivatives based on conformational considerations. Modification
      on the indane ring led to the discovery of compound 22a (INCB9471) that exhibited
      high affinity for CCR5, potent anti-HIV-1 activity, high receptor selectivity,
      excellent oral bioavailability, and a tolerated safety profile. INCB9471 has
      entered human clinical trials. 

PMID- 24900236
TI  - Discovery of Dual VEGFR-2 and Tubulin Inhibitors with in Vivo Efficacy.
AB  - In an effort to develop potent, orally bioavailable compounds for the treatment
      of neoplastic diseases, we developed a class of dual VEGFR-2 kinase and tubulin
      inhibitors. Targeting the VEGFR receptor kinase and tubulin structure allows for
      inhibition of both tumor cells and tumor vasculature. Previously, a combination
      of two compounds, a VEGF receptor tyrosine kinase inhibitor and tubulin agent,
      was demonstrated to produce an enhanced antitumor response in animal studies. We
      have reaffirmed their results, with the added benefit that both activities are
      found in one compound. 

PMID- 24900237
TI  - Discovery of a potent inhibitor of anaplastic lymphoma kinase with in vivo
      antitumor activity.
AB  - A series of novel 7-amino-1,3,4,5-tetrahydrobenzo[b]azepin-2-one derivatives
      within the diaminopyrimidine class of kinase inhibitors were identified that
      target anaplastic lymphoma kinase (ALK). These inhibitors are potent against ALK
      in an isolated enzyme assay and inhibit autophosphorylation of the oncogenic
      fusion protein NPM-ALK in anaplastic large cell lymphoma (ALCL) cell lines. The
      lead inhibitor 15, which incorporates a bicyclo[2.2.1]hept-5-ene ring system in
      place of an aryl moiety, activates the pro-apoptotic caspases (3 and 7) and
      displays selective cytotoxicity against ALK-positive ALCL cells. Furthermore, 15
      provides more than 40-fold selectivity against the structurally related insulin
      receptor, is orally bioavailable in multiple species, and displays in vivo
      antitumor efficacy when dosed orally in ALK-positive ALCL tumor xenografts in
      Scid mice. 

PMID- 24900238
TI  - Design of a high fragment efficiency library by molecular graph theory.
AB  - Molecular graph theory was used to design a unique and diverse, high-efficiency
      fragment screening collection. A data set retrieved from the annotated database
      AurSCOPE GPS was used as the reference set, and the GDB-13 database, a virtual
      library of enumerated organic molecules, was used as a source for the fragment
      selection. The data graph collection of Discngine as implemented in PipelinePilot
      was applied to perform the graph pharmacophore similarity matching between the
      reference and the GDB-13 data sets, leading to the ultimate fragment screening
      library. The relevance of this unique fragment collection was demonstrated by
      means of a virtual screening exercise using human trypsin as a test case. Several
      novel entities with high similarity to known trypsin inhibitors were identified
      in the in silico exercise. The application of this unique, high fragment
      efficiency collection to other protein targets in the framework of fragment-based
      drug discovery is warranted. 

PMID- 24900239
TI  - Short-acting T-type calcium channel antagonists significantly modify sleep
      architecture in rodents.
AB  - A novel phenyl acetamide series of short-acting T-type calcium channel
      antagonists has been identified and evaluated using in vitro and in vivo assays.
      Heterocycle substitutions of the 4-position of the phenyl acetamides afforded
      potent and selective antagonists that exhibited desired short plasma half-lives
      across preclinical species. Lead compound TTA-A8 emerged as a compound with
      excellent in vivo efficacy as indicated by its significant modulation of rat
      sleep architecture in an EEG telemetry model, favorable pharmacokinetic
      properties, and excellent preclinical safety. TTA-A8 recently progressed into
      human clinical trials, and in line with our predictions, preliminary studies (n =
      12) with a 20 mg oral dose afforded a high C max of 1.82 +/- 0.274 MUM with an
      apparent terminal half-life of 3.0 +/- 1.1 h. 

PMID- 24900240
TI  - Discovery of an Orally Efficacious Imidazo[5,1-f][1,2,4]triazine Dual Inhibitor
      of IGF-1R and IR.
AB  - This report describes the investigation of a series of 5,7-disubstituted
      imidazo[5,1-f][1,2,4]triazine inhibitors of insulin-like growth factor-1 receptor
      (IGF-1R) and insulin receptor (IR). Structure-activity relationship exploration
      and optimization leading to the identification, characterization, and
      pharmacological activity of compound 9b, a potent, selective, well-tolerated, and
      orally bioavailable dual inhibitor of IGF-1R and IR with in vivo efficacy in
      tumor xenograft models, is discussed. 

PMID- 24900241
TI  - Modification at the Lipophilic Domain of RXR Agonists Differentially Influences
      Activation of RXR Heterodimers.
AB  - RXR permissive heterodimers are reported to be activated differently depending
      upon the chemical structure of RXR agonists, but the relationship of agonist
      structure to differential heterodimer activation has not been explored in detail.
      In this study, we performed systematic conversion of the alkoxy side chain of 5a
      (6-[ethyl-(3-isopropoxy-4-isopropylphenyl)amino]nicotinic acid, NEt-3IP) and
      evaluated the RXR-, PPAR/RXR-, and LXR/RXR-agonist activities of the products.
      The cyclopropylmethoxy analogue (5c) showed similar RXR- and LXR/RXR-agonistic
      activities to the benzyloxy analogue (5i) and n-propoxy analogue (5k) but
      exhibited more potent PPAR/RXR-agonistic activity than 5i or 5k. Differential
      modulation of RXR heterodimer-activating ability by conversion of the alkoxy
      group located in the lipophilic domain of the RXR-agonist common structure is
      expected be a useful approach in the design of new RXR agonists for the treatment
      of hyperlipidemia or type 2 diabetes. 

PMID- 24900242
TI  - Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral
      Erythropoietin Secretagogues.
AB  - HIF prolyl 4-hydroxylases (PHD) are a family of enzymes that mediate key
      physiological responses to hypoxia by modulating the levels of hypoxia inducible
      factor 1-alpha (HIF1alpha). Certain benzimidazole-2-pyrazole carboxylates were
      discovered to be PHD2 inhibitors using ligand- and structure-based methods and
      found to be potent, orally efficacious stimulators of erythropoietin secretion in
      vivo. 

PMID- 24900243
TI  - Design, Synthesis, and in Vitro Evaluation of Novel Aminomethyl-pyridines as DPP
      4 Inhibitors.
AB  - A collection of novel aminomethyl-pyridines was designed, synthesized, and
      investigated as potential inhibitors of DPP-4. Optimization of the screening hit
      afforded a number of 5-aminomethyl-pyridines with inhibitory activity in the
      nanomolar range. Selected DPP-4 inhibitors were further evaluated for their
      selectivity over the closely related peptidase DPP-8. 5-Aminomethyl-4-(2,4
      dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid cyanomethyl-amide showed
      high potency and excellent DPP-4 selectivity [IC50: 10 (DPP-4) and 6600 nM (DPP
      8)] and no toxicity in mammalian cell culture. 

PMID- 24900245
TI  - Drawing the PDB: Protein-Ligand Complexes in Two Dimensions.
AB  - The two-dimensional representation of molecules is a popular communication medium
      in chemistry and the associated scientific fields. Computational methods for
      drawing small molecules with and without manual investigation are well
      established and widely spread in terms of numerous software tools. Concerning the
      planar depiction of molecular complexes, there is considerably less choice. We
      developed the software PoseView, which automatically generates two-dimensional
      diagrams of macromolecular complexes, showing the ligand, the interactions, and
      the interacting residues. All depicted molecules are drawn on an atomic level as
      structure diagrams; thus, the output plots are clearly structured and easily
      readable for the scientist. We tested the performance of PoseView in a large
      scale application on nearly all druglike complexes of the PDB (approximately
      200000 complexes); for more than 92% of the complexes considered for drawing, a
      layout could be computed. In the following, we will present the results of this
      application study. 

PMID- 24900244
TI  - Facile synthesis of a fluorescent cyclosporin a analogue to study cyclophilin 40
      and cyclophilin 18 ligands.
AB  - There are strong indications for the involvement of cyclophilin 40 in diseases
      caused by misregulation of steroid hormone receptors, like prostate or breast
      cancer. To identify novel inhibitors for this immunophilin, we developed a
      simplified fluorescence polarization assay based on the synthesis of a
      fluorescein-labeled tracer. This tracer was produced by a facile four-step
      synthesis involving Grubbs metathesis and standard amide bond coupling, to label
      cyclosporin A with fluorescein. We show the binding of this tracer to Cyp40 and
      Cyp18 with K D values of 106 +/- 13 or 12 +/- 1 nM, respectively, by analyzing
      the anisotropy change and demonstrate its competition with cyclosporin A. Binding
      data obtained by fluorescence polarization were corroborated by an enzymatic
      activity assay. The described tracer allows for a robust assay in a high
      throughput format to support the development of novel Cyp40 ligands. 

PMID- 24900247
TI  - First Selective CYP11B1 Inhibitors for the Treatment of Cortisol-Dependent
      Diseases.
AB  - Outgoing from an etomidate-based design concept, we succeeded in the development
      of a series of highly active and selective inhibitors of CYP11B1, the key enzyme
      of cortisol biosynthesis, as potential drugs for the treatment of Cushing's
      syndrome and related diseases. Thus, compound 33 (IC50 = 152 nM) is the first
      CYP11B1 inhibitor showing a rather good selectivity toward the most important
      steroidogenic CYP enzymes aldosterone synthase (CYP11B2), the androgen-forming
      CYP17, and aromatase (estrogen synthase, CYP19). 

PMID- 24900248
TI  - Novel Cyclic Phosphinic Acids as GABAC rho Receptor Antagonists: Design,
      Synthesis, and Pharmacology.
AB  - Understanding the role of GABAC receptors in the central nervous system is
      limited due to a lack of specific ligands. Novel gamma-aminobutyric acid (GABA)
      analogues based on 3-(aminomethyl)-1-oxo-1-hydroxy-phospholane 17 and 3-(guanido)
      1-oxo-1-hydroxy-phospholane 19 were investigated to obtain selective GABAC
      receptor antagonists. A compound of high potency (19, K B = 10 MUM) and
      selectivity (greater than 100 times at rho1 GABAC receptors as compared to
      alpha1beta2gamma2L GABAA and GABAB(1b,2) receptors) was obtained. The cyclic
      phosphinic acids (17 and 19) are novel lead agents for developing into more
      potent and selective GABAC receptor antagonists with increased lipophilicity for
      future in vivo studies. 

PMID- 24900249
TI  - Study of kaempferol glycoside as an insulin mimic reveals glycon to be the key
      active structure.
AB  - Diabetes mellitus is increasing in prevalence with patient numbers rising
      throughout the world. Current treatments for diabetes mellitus focus on control
      of blood glucose levels. Certain kinds of flavonoids or their glycosides
      stimulate cells to improve glucose uptake and lower blood glucose levels. We
      synthesized kaempferol 3-O-neohesperidoside (1), a naturally occurring substance
      present in Cyathea phalerata Mart., reported to mimic the action of insulin.
      Synthetic 1 promoted glucose uptake in the cultured cell line, L6. Further
      studies to determine the core structure responsible for this activity using
      synthetic compounds revealed neohesperidose to be the primary pharmacophore.
      These findings support the use of certain saccharides as a potential novel
      treatment for diabetes mellitus by replacing or supporting insulin. 

PMID- 24900250
TI  - Kinase inhibition by deoxy analogues of the resorcylic lactone L-783277.
AB  - The natural product L-783277 is a resorcylic lactone type covalent kinase
      inhibitor. We have prepared the 5'-deoxy analogue of L-783277 (1) in a
      stereoselective fashion. Remarkably, this analogue retains almost the full kinase
      inhibitory potential of natural L-783277, with low nanomolar IC50 values against
      the most sensitive kinases, and it exhibits essentially the same selectivity
      profile (within the panel of 39 kinases investigated). In contrast, removal of
      both the 4'- and the 5'-hydroxyl groups leads to a more significant reduction in
      kinase inhibitory activity and so does a change in the geometry of the C7'-C8'
      double bond in 1 from Z to E. These findings offer new perspectives for the
      design of second generation resorcylic lactone-based kinase inhibitors. 

PMID- 24900251
TI  - Automated Lead Optimization of MMP-12 Inhibitors Using a Genetic Algorithm.
AB  - Traditional lead optimization projects involve long synthesis and testing cycles,
      favoring extensive structure-activity relationship (SAR) analysis and molecular
      design steps, in an attempt to limit the number of cycles that a project must run
      to optimize a development candidate. Microfluidic-based chemistry and biology
      platforms, with cycle times of minutes rather than weeks, lend themselves to
      unattended autonomous operation. The bottleneck in the lead optimization process
      is therefore shifted from synthesis or test to SAR analysis and design. As such,
      the way is open to an algorithm-directed process, without the need for detailed
      user data analysis. Here, we present results of two synthesis and screening
      experiments, undertaken using traditional methodology, to validate a genetic
      algorithm optimization process for future application to a microfluidic system.
      The algorithm has several novel features that are important for the intended
      application. For example, it is robust to missing data and can suggest compounds
      for retest to ensure reliability of optimization. The algorithm is first
      validated on a retrospective analysis of an in-house library embedded in a larger
      virtual array of presumed inactive compounds. In a second, prospective experiment
      with MMP-12 as the target protein, 140 compounds are submitted for synthesis over
      10 cycles of optimization. Comparison is made to the results from the full
      combinatorial library that was synthesized manually and tested independently. The
      results show that compounds selected by the algorithm are heavily biased toward
      the more active regions of the library, while the algorithm is robust to both
      missing data (compounds where synthesis failed) and inactive compounds. This
      publication places the full combinatorial library and biological data into the
      public domain with the intention of advancing research into algorithm-directed
      lead optimization methods. 

PMID- 24900252
TI  - Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase
      Inhibitors.
AB  - Phospoinositide-3-kinases (PI3K) are important oncology targets due to the
      deregulation of this signaling pathway in a wide variety of human cancers. A
      series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been
      reported as potent inhibitors of PI3Ks. Herein, we describe the structure-guided
      optimization of these pyrimidines with a focus on replacing the phenol moiety,
      while maintaining potent target inhibition and improving in vivo properties. A
      series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently
      inhibit PI3K, were discovered. Within this series a compound, 17, was identified
      with suitable pharmacokinetic (PK) properties, which allowed for the
      establishment of a PI3K PK/pharmacodynamic-efficacy relationship as determined by
      in vivo inhibition of AKT(Ser473) phosphorylation and tumor growth inhibition in
      a mouse A2780 tumor xenograft model. 

PMID- 24900253
TI  - Discovery of MK-5046, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for
      the Treatment of Obesity.
AB  - We report the development and characterization of compound 22 (MK-5046), a
      potent, selective small molecule agonist of BRS-3 (bombesin receptor subtype-3).
      In pharmacological testing using diet-induced obese mice, compound 22 caused
      mechanism-based, dose-dependent reductions in food intake and body weight. 

PMID- 24900254
TI  - Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.
AB  - Kisspeptin is a member of the RFamide neuropeptide family that is implicated in
      gonadotropin secretion. Because kisspeptin-GPR54 signaling is implicated in the
      neuroendocrine regulation of reproduction, GPR54 ligands represent promising
      therapeutic agents against endocrine secretion disorders. In the present study,
      the selectivity profiles of GPR54 agonist peptides were investigated for several
      GPCRs, including RFamide receptors. Kisspeptin-10 exhibited potent binding and
      activation of neuropeptide FF receptors (NPFFR1 and NPFFR2). In contrast, short
      peptide agonists bound with much lower affinity to NPFFRs while showing
      relatively high selectivity toward GPR54. The possible localization of secondary
      kisspeptin targets was also demonstrated by variation in the levels of GnRH
      release from the median eminence and the type of GPR54 agonists used. Negligible
      affinity of the reported NPFFR ligands to GPR54 was observed and indicates the
      unidirectional cross-reactivity between both ligands. 

PMID- 24900255
TI  - Benzimidazoles as Potent and Orally Active mGlu5 Receptor Antagonists with an
      Improved PK Profile.
AB  - A focused chemical optimization effort of compound 1 based on metabolite
      elucidation is described, resulting in 15i, a highly potent and selective mGlu5
      receptor antagonist with an improved pharmacokinetic profile compared to 1.
      Characterization of 15i in vivo in the fear-potentiated startle (FPS) paradigm
      revealed a robust reduction of conditioned fear behavior. This effect nicely
      correlates with the rat brain pharmacokinetics. 

PMID- 24900256
TI  - Development of Selective LH Receptor Agonists by Heterodimerization with a FSH
      Receptor Antagonist.
AB  - The structural resemblance of the luteinizing hormone receptor (LHR) and follicle
      stimulating hormone receptor (FSHR) impedes selective agonistic targeting of one
      of those by low molecular weight (LMW) ligands. In the present study, we describe
      a series of dimeric ligands consisting of a LMW agonist with dual activity on the
      FSHR and the LHR linked to a selective FSHR antagonist. Biological evaluation
      shows these compounds to be potent and selective LHR agonists, since no agonistic
      activity on the FSHR was observed. Equimolar mixing of the monomeric counterparts
      did not yield the pharmacological profile observed for the heterodimeric ligands,
      and FSHR agonism of the monomeric LHR agonist was still observed. The here
      described results show that ligands with unique pharmacological profiles can be
      obtained by dimerizing monomeric molecules with distinct apposite properties. 

PMID- 24900257
TI  - Optimization of Pharmacokinetics through Manipulation of Physicochemical
      Properties in a Series of HCV Inhibitors.
AB  - A novel series of HCV replication inhibitors based on a pyrido[3,2-d]pyrimidine
      core were optimized for pharmacokinetics (PK) in rats. Several associations
      between physicochemical properties and PK were identified and exploited to guide
      the design of compounds. In addition, a simple new metric that may aid in the
      prediction of bioavailability for compounds with higher polar surface area is
      described (3*HBD-cLogP). 

PMID- 24900258
TI  - 3D Pharmacophore Model-Assisted Discovery of Novel CDC7 Inhibitors.
AB  - A ligand-based 3D pharmacophore model for serine/threonine kinase CDC7 inhibition
      was created and successfully applied in the discovery of novel 2-(heteroaryl)-6,7
      dihydrothieno[3,2-c]pyridin-4(5H)-ones. The pharmacophore model provided a
      hypothesis for lead generation missed by docking to a homology model. Medicinal
      chemistry exploration of the series revealed clear structure-activity
      relationships consistent with the pharmacophore model and pointed to further
      optimization opportunities. 

PMID- 24900259
TI  - Exploiting Fluorescence Lifetime Plasticity in FLIM: Target Molecule Localization
      in Cells and Tissues.
AB  - The mechanisms of drug-receptor interactions and the controlled delivery of drugs
      via biodegradable and biocompatible nanoparticulate carriers are active research
      fields in nanomedicine. Many clinically used drugs target G-protein coupled
      receptors (GPCRs) due to the fact that signaling via GPCRs is crucial in
      physiological and pathological processes and thus central for the function of
      biological systems. In this letter, a fast and reliable ratiometric fluorescence
      lifetime imaging microscopy (rmFLIM) approach is described to analyze the
      distribution of protein-ligand complexes in the cellular context. Binding of the
      fluorescently labeled antagonist naloxone to the G-protein coupled MU-opioid
      receptor is used as an example. To show the broad applicability of the rmFLIM
      method, we extended this approach to investigate the distribution of polymer
      based nanocarriers in histological liver sections. 

PMID- 24900260
TI  - Structure-based ligand design of novel bacterial RNA polymerase inhibitors.
AB  - Bacterial RNA polymerase (RNAP) is essential for transcription and is an
      antibacterial target for small molecule inhibitors. The binding region of
      myxopyronin B (MyxB), a bacterial RNAP inhibitor, offers the possibility of new
      inhibitor design. The molecular design program SPROUT has been used in
      conjunction with the X-ray cocrystal structure of Thermus thermophilus RNAP with
      MyxB to design novel inhibitors based on a substituted pyridyl-benzamide
      scaffold. A series of molecules, with molecular masses <350 Da, have been
      prepared using a simple synthetic approach. A number of these compounds inhibited
      Escherichia coli RNAP. 

PMID- 24900261
TI  - An Invitation to Open Innovation in Malaria Drug Discovery: 47 Quality Starting
      Points from the TCAMS.
AB  - In 2010, GlaxoSmithKline published the structures of 13533 chemical starting
      points for antimalarial lead identification. By using an agglomerative structural
      clustering technique followed by computational filters such as antimalarial
      activity, physicochemical properties, and dissimilarity to known antimalarial
      structures, we have identified 47 starting points for lead optimization. Their
      structures are provided. We invite potential collaborators to work with us to
      discover new clinical candidates. 

PMID- 24900262
TI  - Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for
      Clinical Utility.
AB  - Structure guided optimization of a series of nonpeptidic alkyl amine renin
      inhibitors allowed the rational incorporation of additional polar functionality.
      Replacement of the cyclohexylmethyl group occupying the S1 pocket with a (R)
      (tetrahydropyran-3-yl)methyl group and utilization of a different attachment
      point led to the identification of clinical candidate 9. This compound
      demonstrated excellent selectivity over related and unrelated off-targets, >15%
      oral bioavailability in three species, oral efficacy in a double transgenic rat
      model of hypertension, and good exposure in humans. 

PMID- 24900263
TI  - 4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and
      Selective Agonist of S1P1.
AB  - The sphingosine-1-phosphate-1 receptor (S1P1) and its endogenous ligand
      sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from
      the lymphatic system. Herein, we disclose 4-methoxy-N-[2
      (trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of
      a synthetic S1P1 agonist lacking a polar headgroup, which is shown to effect
      dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a
      single oral dose (1 mg/kg). The excellent potency that 8 exhibits toward S1P1
      (EC50 = 0.035 MUM, 96% efficacy) and the >100-fold selectivity that it displays
      against receptor subtypes S1P2-5 suggest that it may serve as a valuable tool to
      understand the clinical relevance of selective S1P1 agonism. 

PMID- 24900265
TI  - Aryltriflates as a Neglected Moiety in Medicinal Chemistry: A Case Study from a
      Lead Optimization of CXCL8 Inhibitors.
AB  - Interleukin-8 and growth related oncogene-alpha-chemokines (formerly CXCL8 and
      CXCL1, respectively) mediate chemotaxis of neutrophils to inflammatory sites via
      interactions with two transmembrane receptors, the type A CXCL8 receptor (CXCR1)
      and the type B CXCL8 receptor (CXCR2). In a previous work, we published the
      molecular modeling-driven structure activity relationship (SAR) results
      culminated in the discovery of R-(-)-2-[(4'-trifluoromethanesulphonyloxy)phenyl]
      N-methanesulfonyl propionamide (19), in which an unusual aryltriflate moiety was
      embedded. Although triflates are broadly used in organic synthesis, this group is
      scarcely used in medicinal chemistry programs. Here we detail the drug profiling
      driven approach used for the selection and characterization of 19, the most
      potent dual CXCR1 and CXCR2 noncompetitive inhibitor described to date. Reported
      data suggest that the aryltriflate moiety might represent a valid choice for the
      selection of clinical candidates with suitable druglike properties. 

PMID- 24900264
TI  - The Discovery of VX-745: A Novel and Selective p38alpha Kinase Inhibitor.
AB  - The synthesis of novel, selective, orally active 2,5-disubstituted 6H
      pyrimido[1,6-b]pyridazin-6-one p38alpha inhibitors is described. Application of
      structural information from enzyme-ligand complexes guided the selection of
      screening compounds, leading to the identification of a novel class of p38alpha
      inhibitors containing a previously unreported bicyclic heterocycle core.
      Advancing the SAR of this series led to the eventual discovery of 5-(2,6
      dichlorophenyl)-2-(2,4-difluorophenylthio)-6H-pyrimido[1,6-b]pyridazin-6-one (VX
      745). VX-745 displays excellent enzyme activity and selectivity, has a favorable
      pharmacokinetic profile, and demonstrates good in vivo activity in models of
      inflammation. 

PMID- 24900266
TI  - Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I
      PI3 Kinase Inhibitor for Treating Cancer.
AB  - Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the
      deregulation of this signaling pathway in a wide variety of human cancers. Herein
      we describe the structure guided optimization of a series of 2-morpholino, 4
      substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were
      improved by modulating the electronics of the 6-position heterocycle, and the
      overall druglike properties were fine-tuned further by modification of the 4
      position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines
      are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent
      cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway
      deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the
      discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the
      treatment of cancer. 

PMID- 24900267
TI  - Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable gamma
      Secretase Modulator.
AB  - We have investigated a novel series of acid-derived gamma-secretase modulators as
      a potential treatment of Alzheimer's disease. Optimization based on cellular
      potency and brain pharmacodynamics after oral dosing led to the discovery of 10a
      (BIIB042). Compound 10a is a potent gamma-secretase modulator, which lowered
      Abeta42, increased Abeta38, but had little to no effect on Abeta40 levels both in
      vitro and in vivo. In addition, compound 10a did not affect Notch signaling in
      our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic
      parameters in multiple species. Oral administration of 10a significantly reduced
      brain Abeta42 levels in CF-1 mice and Fischer rats, as well as plasma Abeta42
      levels in cynomolgus monkeys. Compound 10a was selected as a candidate for
      preclinical safety evaluation. 

PMID- 24900268
TI  - Mannitol Bis-phosphate Based Inhibitors of Fructose 1,6-Bisphosphate Aldolases.
AB  - Several 5-O-alkyl- and 5-C-alkyl-mannitol bis-phosphates were synthesized and
      comparatively assayed as inhibitors of fructose bis-phosphate aldolases (Fbas)
      from rabbit muscle (taken as surrogate model of the human enzyme) and from
      Trypanosoma brucei. A limited selectivity was found in several instances.
      Crystallographic studies confirm that the 5-O-methyl derivative binds
      competitively with substrate and the 5-O-methyl moiety penetrating deeper into a
      shallow hydrophobic pocket at the active site. This observation can lead to the
      preparation of selective competitive or irreversible inhibitors of the parasite
      Fba. 

PMID- 24900269
TI  - Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor
      Activity.
AB  - Highly selective PI3K inhibitors with subnanomolar PI3Kalpha potency and greater
      than 7000-fold selectivity against mTOR kinase were discovered through structure
      based drug design (SBDD). These tetra-substituted thiophenes were also
      demonstrated to have good in vitro cellular potency and good in vivo oral
      antitumor activity in a mouse PI3K driven NCI-H1975 xenograft tumor model.
      Compounds with the desired human PK predictions and good in vitro ADMET
      properties were also identified. In this communication, we describe the rationale
      behind the installation of a critical triazole moiety to maintain the intricate H
      bonding network within the PI3K receptor leading to both better potency and
      selectivity. Furthermore, optimization of the C-4 phenyl group was exploited to
      maximize the compounds mTOR selectivity. 

PMID- 24900270
TI  - Synthesis and Evaluation of the Metabolites of AMG 221, a Clinical Candidate for
      the Treatment of Type 2 Diabetes.
AB  - All eight of the major active metabolites of (S)-2-((1S,2S,4R)
      bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221,
      compound 1), an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 that has
      entered the clinic for the treatment of type 2 diabetes, were synthetically
      prepared and confirmed by comparison with samples generated in liver microsomes.
      After further profiling, we determined that metabolite 2 was equipotent to 1 on
      human 11beta-HSD1 and had lower in vivo clearance and higher bioavailability in
      rat and mouse. Compound 2 was advanced into a pharmacodynamic model in mouse
      where it inhibited adipose 11beta-HSD1 activity. 

PMID- 24900271
TI  - Type 1 phototherapeutic agents, part I: preparation and cancer cell viability
      studies of novel photolabile sulfenamides.
AB  - Novel type 1 phototherapeutic agents based on compounds containing S-N bonds
      (sulfenamides) were synthesized, assessed for free radical generation, and
      evaluated in vitro for cell death efficacy in four cancer cell lines (U937,
      HTC11, KB, and HT29). All of the compounds were found to produce copious free
      radicals upon photoexcitation with UV-A and/or UV-B light, as determined by
      electron spin resonance spectroscopy. Among the sulfenamides, the most potent
      compounds were derived from dibenzazepine 7b and dihydroacridine 8b as determined
      in all of the four cancer cell lines. 

PMID- 24900272
TI  - Homology Model and Docking-Based Virtual Screening for Ligands of the sigma1
      Receptor.
AB  - This study presents for the first time the 3D model of the sigma1 receptor
      protein as obtained from homology modeling techniques, shows the applicability of
      this structure to docking-based virtual screening, defines a computational
      strategy to optimize the results based on a combination of 3D pharmacophore-based
      docking and MM/PBSA free energy of binding scoring, and provides evidence that
      these in silico models and recipes are powerful tools on which virtual screening
      of new sigma1 ligands can be based. In particular, the validation of the
      applicability of docking-based virtual screening to homology models is of utmost
      importance, since no crystal structure is available to date for the sigma1
      receptor, and this missing information still constitutes a major hurdle for a
      rational ligand design for this important protein target. 

PMID- 24900273
TI  - Cyclopropyl Carboxamides: A New Oral Antimalarial Series Derived from the Tres
      Cantos Anti-Malarial Set (TCAMS).
AB  - Rapid triaging of three series of related hits selected from the Tres Cantos Anti
      Malarial Set (TCAMS) are described. A triazolopyrimidine series was deprioritized
      due to delayed inhibition of parasite growth. A lactic acid series has
      derivatives with IC50 < 500 nM in a standard Plasmodium falciparum in vitro whole
      cell assay (Pf assay) but shows half-lives of < 30 min in both human and murine
      microsomes. Compound 19, from a series of cyclopropyl carboxamides, is a highly
      potent in vitro inhibitor of P. falciparum (IC50 = 3 nM) and has an oral
      bioavailability of 55% in CD-1 mice and an ED90 of 20 mg/kg after oral dosing in
      a nonmyelo-depleted P. falciparum murine model. 

PMID- 24900274
TI  - Synthesis of C-Pseudonucleosides Bearing Thiazolidin-4-one as a Novel Potential
      Immunostimulating Agent.
AB  - Several novel C-pseudonucleosides bearing thiazolidin-4-one were synthesized by
      one-pot three-component condensation using unprotected sugar aldehyde at room
      temperature, and their effects on T cells, B cells, the cytokine secretion of IL
      2, IL-4, and IFN-gamma, T cell-associated molecules (CD3, CD4, CD8), and B cell
      associated molecules (CD19) were first evaluated. The experimental data
      demonstrated that such thiazolidin-4-one C-pseudonucleosides hold potential as
      immunostimulating agents. 

PMID- 24900275
TI  - Identification of a Potent and Selective Cannabinoid CB1 Receptor Antagonist from
      Auxarthron reticulatum.
AB  - The fungus Auxarthron reticulatum derived from the marine sponge Ircinia
      variabilis produced the diketopiperazine alkaloid amauromine (1) and the
      quinolinone methyl-penicinoline (2). Compound 2 is identical to the reported
      methyl-marinamide, whose structure is herewith revised. In radioligand binding
      studies at human cannabinoid CB1 and CB2 receptors recombinantly expressed in
      Chinese hamster ovary (CHO) cells, amauromine (1) was found to exhibit high
      affinity and selectivity for the CB1 receptor (K i = 178 nM). The compound was
      shown to be a neutral CB1 antagonist with a K b value of 66.6 nM determined in
      cAMP assays. Compound 2 exhibited only weak or no effects at CB receptors. To the
      best of our knowledge, compound 1 is the first fungal natural product that shows
      affinity for cannabinoid CB1 receptors. Because of its high antagonistic potency
      and selectivity, it may have potential for use as a drug and/or serve as a lead
      structure for drug development. 

PMID- 24900276
TI  - Copper-Free Click for PET: Rapid 1,3-Dipolar Cycloadditions with a Fluorine-18
      Cyclooctyne.
AB  - The strain-promoted click 1,3-dipolar cycloaddition reactions involving azides
      and cyclooctynes for the synthesis of triazoles offer the advantage of being able
      to be performed in biological settings via copper-free chemistries. While
      strained reagents conjugated to optical dyes and radiometal conjugates have been
      reported, cyclooctyne reagents labeled with fluorine-18 ((18)F) and
      radiochemically evaluated in a copper-free click reaction have yet to be
      explored. This report describes the conversion of a bifunctional
      azadibenzocyclooctyne (ADIBO) amine to the (18)F-labeled cyclooctyne 4, the
      subsequent fast copper-free 1,3-dipolar cycloaddition reaction with alkyl azides
      at 37  degrees C (>70% radiochemical conversion in 30 min), and biological
      evaluations (serum stability of >95% at 2 h). These findings demonstrate the
      excellent reactivity of the (18)F-labeled cyclooctyne 4 with readily available
      azides that will allow future work focusing on rapid copper-free in vitro and in
      vivo click chemistries for PET imaging using (18)F-labeled cyclooctyne
      derivatives of ADIBO. 

PMID- 24900277
TI  - Development of Polar Adenosine A2A Receptor Agonists for Inflammatory Bowel
      Disease: Synergism with A2B Antagonists.
AB  - Adenosine A2A receptor agonists for the local treatment of inflammatory bowel
      disease (IBS) were designed and synthesized. Polar groups were introduced to
      prevent peroral absorption and subsequent systemic, e.g., hypotensive, side
      effects. 4-(2-{6-Amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5
      (hydroxymethyl)tetrahydrofuran-2-yl]-9H-purin-2-ylthio}ethyl)benzenesulfonic acid
      (7, PSB-0777) was selected for further evaluation in rat ileum/jejunum
      preparations in ex vivo experiments. Compound 7 significantly improved impaired
      acetylcholine-induced contractions induced by 2,4,6-trinitrobenzenesulfonic acid
      and showed synergism with an A2B-selective antagonist. Thus, nonabsorbable,
      locally active A2A agonists, as a monotherapy or in combination with an A2B
      antagonist, may be an efficient novel treatment for IBS, preventing the severe
      systemic side effects of known A2A agonists. 

PMID- 24900278
TI  - Discovery of a Potent Retinoid X Receptor Antagonist Structurally Closely Related
      to RXR Agonist NEt-3IB.
AB  - We discovered a potent retinoid X receptor (RXR) antagonist, 6-[N-ethyl-N-(5
      isobutoxy-4-isopropyl-2-(E)-styrylphenyl)amino]nicotinic acid (13e), that is
      structurally closely related to the RXR full agonist 6-[N-ethyl-N-(3-isobutoxy-4
      isopropylphenyl)amino]nicotinic acid (NEt-3IB) (4). Compound 13e was synthesized
      via a simple route from 11, a methyl ester precursor of 4. Because 11 possesses
      high electrophilic reactivity because of the amino and alkoxy groups, it was
      readily transformed to 12 by iodization, and the iodine atom of 12 was converted
      to a C-C or C-N bond by means of palladium-catalyzed reaction to afford 13.
      Transcriptional activation assay revealed that 13g (in which the iodine atom was
      replaced with an amino group) is a weak RXR agonist, while 13d (a phenyl group),
      13e (a styryl group), and 13f (an anilino group) are RXR antagonists. Among them,
      13e was found to be more potent than the known RXR antagonist PA452 (9). 

PMID- 24900279
TI  - Synthesis of marine-derived 3-alkylpyridinium alkaloids with potent antiprotozoal
      activity.
AB  - Given the pressing need for new antiprotozoal drugs without cross-resistance with
      current (failing) chemotherapy, we have explored 3-tridecylpyridinium alkaloids
      (3TPAs), derivatives of viscosamine, as antiparasitic agents. We have developed a
      simple synthetic route toward viscosamine and related cyclic and linear monomers
      and oligomers. Evaluation for cytotoxicity on the protozoan parasites Trypanosoma
      brucei, Leishmania spp., and Plasmodium falciparum revealed several 3TPAs with
      antiprotozoal activity in the nanomolar range. Their promising selectivity index
      in vitro prompted us to study the dynamics of cytotoxicity on trypanosomes in
      more detail. Parasites were killed relatively slowly at therapeutically safe
      concentrations, in a process that did not target the cell cycle. Clearance of T.
      brucei cultures was observed at drug concentrations of 1-10 MUM. 

PMID- 24900280
TI  - Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable
      CCR2 Antagonist.
AB  - We report the discovery of a new (S)-3-aminopyrrolidine series of CCR2
      antagonists. Structure-activity relationship studies on this new series led to
      the identification of 17 (INCB8761/PF-4136309) that exhibited potent CCR2
      antagonistic activity, high selectivity, weak hERG activity, and an excellent in
      vitro and in vivo ADMET profile. INCB8761/PF-4136309 has entered human clinical
      trials. 

PMID- 24900281
TI  - Potent and Selective Inhibitors of Long Chain l-2-Hydroxy Acid Oxidase Reduced
      Blood Pressure in DOCA Salt-Treated Rats.
AB  - l-2-Hydroxy acid oxidase (Hao2) is a peroxisomal enzyme with predominant
      expression in the liver and kidney. Hao2 was recently identified as a candidate
      gene for blood pressure quantitative trait locus in rats. To investigate a
      pharmacological role of Hao2 in the management of blood pressure, selective Hao2
      inhibitors were developed. Optimization of screening hits 1 and 2 led to the
      discovery of compounds 3 and 4 as potent and selective rat Hao2 inhibitors with
      pharmacokinetic properties suitable for in vivo studies in rats. Treatment with
      compound 3 or 4 resulted in a significant reduction or attenuation of blood
      pressure in an established or developing model of hypertension,
      deoxycorticosterone acetate-treated rats. This is the first report demonstrating
      a pharmacological benefit of selective Hao2 inhibitors in a relevant model of
      hypertension. 

PMID- 24900282
TI  - Toward Overcoming Staphylococcus aureus Aminoglycoside Resistance Mechanisms with
      a Functionally Designed Neomycin Analogue.
AB  - Deoxygenation of the diol groups in rings A and D of neomycin in combination with
      the introduction of an N1-(l)-HABA group in the 2-deoxystreptamine subunit (ring
      B) leads to a novel and potent antibiotic (1) with activity against strains of S.
      aureus carrying known aminoglycoside resistance determinants, as well as against
      an extended panel of Methicillin-resistant S. aureus isolates (n = 50).
      Antibiotic 1 displayed >64 fold improvement in MIC50 and MIC90 against this MRSA
      collection when compared to the clinically relevant aminoglycosides amikacin and
      gentamicin. The synthesis was achieved in six steps and 15% overall yield. 

PMID- 24900284
TI  - Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of
      Carboxylic Acids.
AB  - Antagonism of the CRTH2 receptor represents a very attractive target for a
      variety of allergic diseases. Most CRTH2 antagonists known to date possess a
      carboxylic acid moiety, which is essential for binding. However, potential acid
      metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in
      humans. In this communication, we describe a new series of compounds that lack
      the carboxylic acid moiety. Compounds with high affinity (K i < 10 nM) for the
      receptor have been identified. Subsequent optimization succeeded in reducing the
      high metabolic clearance of the first compounds in human and rat liver
      microsomes. At the same time, inhibition of the CYP isoforms was optimized,
      giving rise to stable compounds with an acceptable CYP inhibition profile (IC50
      CYP2C9 and 2C19 > 1 MUM). Taken together, these data show that compounds devoid
      of carboxylic acid groups could represent an interesting alternative to current
      CRTH2 antagonists in development. 

PMID- 24900285
TI  - Supramolecular ferric porphyrins as cyanide receptors in aqueous solution.
AB  - All fundamental data about binding of the cyanide to a supramolecular complex
      composed of a per-O-methylated beta-cyclodextrin dimer having an imidazole linker
      (Im3CD) and an anionic ferric porphyrin (Fe((III))TPPS) indicate that the
      Fe((III))TPPS/Im3CD complex is much better as an cyanide receptor in vivo than
      hydroxocobalamin, whose cyanide binding ability is lowered by its strong binding
      to serum proteins in the blood. 

PMID- 24900283
TI  - Discovery of benzodiazepine sulfonamide-based bombesin receptor subtype 3
      agonists and their unusual chirality.
AB  - We report herein the discovery of benzodiazepine sulfonamide-based bombesin
      receptor subtype 3 (BRS-3) agonists and their unusual chirality. Starting from a
      high-throughput screening lead, we prepared a series of BRS-3 agonists with
      improved potency and pharmacokinetic properties, of which compound 8a caused
      mechanism-based, dose-dependent food intake reduction and body weight loss after
      oral dosing in diet-induced obese mice. This effort also led to the discovery of
      a novel family of chiral molecules originated from the conformationally
      constrained seven-membered diazepine ring. 

PMID- 24900286
TI  - Benzofuran Derivatives as Potent, Orally Active S1P1 Receptor Agonists: A
      Preclinical Lead Molecule for MS.
AB  - We have discovered novel benzofuran-based S1P1 agonists with excellent in vitro
      potency and selectivity. 1-((4-(5-Benzylbenzofuran-2-yl)-3-fluorophenyl)methyl)
      azetidine-3-carboxylic acid (18) is a potent S1P1 agonist with >1000* selectivity
      over S1P3. It demonstrated a good in vitro ADME profile and excellent oral
      bioavailability across species. Dosed orally at 0.3 mg/kg, 18 significantly
      reduced blood lymphocyte counts 24 h postdose and demonstrated efficacy in a
      mouse EAE model of relapsing MS. 

PMID- 24900288
TI  - Discovery of AMG 369, a Thiazolo[5,4-b]pyridine Agonist of S1P1 and S1P5.
AB  - The optimization of a series of thiazolopyridine S1P1 agonists with limited
      activity at the S1P3 receptor is reported. These efforts resulted in the
      discovery of 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo-[5,4-b]pyridin-2
      yl)benzyl)azetidine-3-carboxylic acid (5d, AMG 369), a potent dual S1P1/S1P5
      agonist with limited activity at S1P3 and no activity at S1P2/S1P4. Dosed orally
      at 0.1 mg/kg, 5d is shown to reduce blood lymphocyte counts 24 h postdose and
      delay the onset and reduce the severity of experimental autoimmune
      encephalomyelitis in rat. 

PMID- 24900287
TI  - Discovery of a Potent, S1P3-Sparing Benzothiazole Agonist of Sphingosine-1
      Phosphate Receptor 1 (S1P1).
AB  - Optimization of a benzofuranyl S1P1 agonist lead compound (3) led to the
      discovery of 1-(3-fluoro-4-(5-(2-fluorobenzyl)benzo[d]thiazol-2
      yl)benzyl)azetidine-3-carboxylic acid (14), a potent S1P1 agonist with minimal
      activity at S1P3. Dosed orally at 0.3 mg/kg, 14 significantly reduced blood
      lymphocyte counts 24 h postdose and attenuated a delayed type hypersensitivity
      (DTH) response to antigen challenge. 

PMID- 24900289
TI  - Identification of potent and selective glucosylceramide synthase inhibitors from
      a library of N-alkylated iminosugars.
AB  - Glucosylceramide synthase (GCS) is an important target for clinical drug
      development for the treatment of lysosomal storage disorders and a promising
      target for combating type 2 diabetes. Iminosugars are useful leads for the
      development of GCS inhibitors; however, the effective iminosugar type GCS
      inhibitors reported have some unwanted cross-reactivity toward other glyco
      processing enzymes. In particular, iminosugar type GCS inhibitors often also
      inhibit to some extent human acid glucosylceramidase (GBA1) and the nonlysosomal
      glucosylceramidase (GBA2), the two enzymes known to process glucosylceramide. Of
      these, GBA1 itself is a potential drug target for the treatment of the lysosomal
      storage disorder, Gaucher disease, and selective GBA1 inhibitors are sought after
      as potential chemical chaperones. The physiological importance of GBA2 in
      glucosylceramide processing in relation to disease states is less clear, and
      here, selective inhibitors can be of use as chemical knockout entities. In this
      communication, we report our identification of a highly potent and selective N
      alkylated l-ido-configured iminosugar. In particular, the selectivity of 27 for
      GCS over GBA1 is striking. 

PMID- 24900290
TI  - Design, Synthesis, and Preclinical Characterization of the Selective Androgen
      Receptor Modulator (SARM) RAD140.
AB  - This report describes the discovery of RAD140, a potent, orally bioavailable,
      nonsteroidal selective androgen receptor modulator (SARM). The characterization
      of RAD140 in several preclinical models of anabolic androgen action is also
      described. 

PMID- 24900291
TI  - Discovery of PSI-353661, a Novel Purine Nucleotide Prodrug for the Treatment of
      HCV Infection.
AB  - Hepatitis C virus afflicts approximately 180 million people worldwide, and the
      development of direct acting antivirals may offer substantial benefit compared to
      the current standard of care. Accordingly, prodrugs of 2'-deoxy-2'-fluoro-2'-C
      methylguanosine monophosphate analogues were prepared and evaluated for their
      anti-HCV efficacy and tolerability. These prodrugs demonstrated >1000 fold
      greater potency than the parent nucleoside in a cell-based replicon assay as a
      result of higher intracellular triphosphate levels. Further optimization led to
      the discovery of the clinical candidate PSI-353661, which has demonstrated strong
      in vitro inhibition against HCV without cytotoxicity and equipotent activity
      against both the wild type and the known S282T nucleoside/tide resistant
      replicon. PSI-353661 is currently in preclinical development for the treatment of
      HCV. 

PMID- 24900292
TI  - TSPO 18 kDa (PBR) Targeted Photosensitizers for Cancer Imaging (PET) and PDT.
AB  - Translocator protein (TSPO) 18 kDa overexpression has been observed in a large
      variety of human cancers, especially breast cancers. PK 11195, an isoquinoline
      analogue, is one of the ligands of highest TSPO binding affinity. Due to the long
      biological half life of our photosensitizers, there is a need to label them with
      a long lived radioisotope, for example I-124. Our objectives are to find
      translocator protein targeted photosensitizers for both tumor imaging (PET) and
      photodynamic therapy (PDT). I-PK 11195 is conjugated with the tumor avid
      photosensitizer HPPH. We find that those two tumor avid components complement
      each other and make the conjugate molecule even more tumor avid; compared to the
      photosensitizer itself, the conjugate is found to show improved PDT efficacy. It
      is concluded that I-PK 11195 can be a good vehicle to deliver radionuclide and
      photosensitizer to TSPO overexpressed tumor regions. Such conjugates could be
      useful for both tumor imaging (PET) and PDT. 

PMID- 24900293
TI  - Discovery of novel cyanamide-based inhibitors of cathepsin C.
AB  - The discovery of potent and selective cyanamide-based inhibitors of the cysteine
      protease cathepsin C is detailed. Optimization of the template with regard to
      plasma stability led to the identification of compound 17, a potent cathepsin C
      inhibitor with excellent selectivity over other cathepsins and potent in vivo
      activity in a cigarette smoke mouse model. 

PMID- 24900294
TI  - Novel 3-aryl indoles as progesterone receptor antagonists for uterine fibroids.
AB  - We report the synthesis and characterization of novel 3-aryl indoles as potent
      and efficacious progesterone receptor (PR) antagonists with potential for the
      treatment of uterine fibroids. These compounds demonstrated excellent selectivity
      over other steroid nuclear hormone receptors such as the mineralocorticoid
      receptor (MR). They were prepared from 2-bromo-6-nitro indole in four to six
      steps using a Suzuki cross-coupling as the key step. Compound 8f was orally
      active in the complement 3 model of progesterone antagonism in the rat uterus and
      demonstrated partial antagonism in the McPhail model of progesterone activity. 

PMID- 24900295
TI  - Discovery of a potent nicotinic Acid receptor agonist for the treatment of
      dyslipidemia.
AB  - Nicotinic acid has been used clinically for decades to control serum
      lipoproteins. Nicotinic acid lowers very low-density lipoprotein (VLDL)
      cholesterol, low-density lipoprotein (LDL)-cholesterol, and lipoprotein-a (LPa),
      and it is also effective in raising high-density lipoprotein (HDL)-cholesterol.
      However, nicotinic acid has several side effects in clinical use. The most
      notable is intense cutaneous vasodilation "flushing" on the upper body and face.
      We discovered a pyranopyrimidinedione series to be nicotinic acid receptor
      agonists. A potent nicotinic acid receptor agonist from this series {5-(3
      cyclopropylpropyl)-2-(difluoromethyl)-3H-pyrano[2,3-d]pyrimidine-4,7-dione}with
      reduced flushing side effect in dogs was identified. 

PMID- 24900296
TI  - Sulfonate-containing thiiranes as selective gelatinase inhibitors.
AB  - Matrix metalloproteinases (MMPs) are important zinc-dependent endopeptidases. Two
      members of this family of enzymes called gelatinases (MMP-2 and MMP-9) have been
      implicated in a number of human diseases, including cancer, neurological and
      cardiovascular diseases, and inflammation, to name a few. We describe in this
      report the preparation and evaluation of two structural types of thiirane
      inhibitors that show selectivity toward gelatinases. The biphenyl series targets
      both gelatinases, whereas the monophenyl analogues exhibit potent inhibition of
      only MMP-2. The latter structural type also exhibits improved water solubility
      and metabolic stability, both traits desirable for progress of these molecules
      forward in gelatinase-dependent animal models of disease. 

PMID- 24900297
TI  - Synthesis and SAR of Thiazolylmethylphenyl Glucoside as Novel C-Aryl Glucoside
      SGLT2 Inhibitors.
AB  - Novel C-aryl glucoside SGLT2 inhibitors containing the thiazole motif were
      designed and synthesized for biological evaluation. Among the compounds assayed,
      thiazole containing furanyl moiety 14v and thiophenyl moiety 14y demonstrated the
      best in vitro inhibitory activity against SGLT2 in this series to date (IC50 =
      0.720 nM for 14v and IC50 = 0.772 nM for 14y). Both of these compounds have been
      further evaluated on a urinary glucose excretion test and the urine volumes
      excreted. 

PMID- 24900298
TI  - Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine
      Receptor Antagonist.
AB  - The structure-activity relationships for a series of pyrazine-based A2B adenosine
      receptor antagonists are described. From this work, LAS101057 (17), a potent,
      selective, and orally efficacious A2B receptor antagonist, was identified as a
      clinical development candidate. LAS101057 inhibits agonist-induced IL-6
      production in human fibroblasts and is active in an ovalbumin (OVA)-sensitized
      mouse model after oral administration, reducing airway hyperresponsiveness to
      methacholine, Th2 cytokine production, and OVA-specific IgE levels. 

PMID- 24900299
TI  - Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and
      Leishmania infantum Proliferation.
AB  - In Leishmania the glutathione/glutathione reductase eukaryotic redox sys-tem is
      replaced by the unique trypanothione/trypanothione reductase (TR) system. In
      vitro, silver is a more effective TR inhibitor than antimony, the first line drug
      against leishmaniasis in most endemic countries, and its mechanism of inhibition
      is similar to that of Sb(III). In particular, silver binds with high affinity to
      the catalytic triad Cys52, Cys57, and His461', thereby inhibiting TR. Here, Ag(0)
      activity was tested on the promastigote and amastigote stages of Leishmania
      infantum using a drug-delivery system consisting in Ag(0) nanoparticles
      encapsulated by ferritin molecules (PfFt-AgNPs). These were able to induce an
      antiproliferative effect on the parasites at metal concentrations lower than
      those used with antimony. 

PMID- 24900300
TI  - Synthesis and antibacterial activity of a novel class of 15-membered macrolide
      antibiotics, "11a-azalides".
AB  - An efficient method for the reconstruction of the 9-dihydroerythromycin A
      macrolactone skeleton has been established. The key steps are oxidative cleavage
      at the 11,12-position and reconstruction after insertion of an appropriate
      functionalized amino alcohol. Novel 15-membered macrolides, we named as "11a
      azalides", were synthesized based on the above methodology and evaluated for
      their antibacterial activity. Among them, (13R)-benzyloxymethyl-11a-azalide
      showed the most potent Streptococcus pneumoniae activity, with improved activity
      against a representative erythromycin-resistant strain compared to clarithromycin
      (CAM). 

PMID- 24900301
TI  - Discovery of a potent and short-acting oral calcilytic with a pulsatile secretion
      of parathyroid hormone.
AB  - Short-acting oral calcilytics, calcium-sensing receptor (CaSR) antagonists, have
      been considered as alternatives for parathyroid hormone (PTH), an injectable bone
      anabolic drug used in the treatment of osteoporosis. Previously, we identified
      aminopropandiol 1, which transiently stimulated endogenous PTH secretion in rats.
      However, the inhibition of cytochrome P450 (CYP) 2D6 and the low bioavailability
      of 1 remain to be solved. Attempts to change the physicochemical properties of
      the highly lipophilic amine 1 by introduction of a carboxylic acid group as well
      as further structural modifications led to the discovery of the highly potent
      biphenylcarboxylic acid 15, with a markedly reduced CYP2D6 inhibition and a
      significantly improved bioavailability. Compound 15 evoked a rapid and transient
      elevation of endogenous PTH levels in rats after oral administration in a dose
      dependent manner at a dose as low as 1 mg/kg. The PTH secretion pattern
      correlated with the pharmacokinetic profile and agreed well with that of the
      exogenous PTH injection which exerts a bone anabolic effect. 

PMID- 24900302
TI  - Hybrid dual aromatase-steroid sulfatase inhibitors with exquisite picomolar
      inhibitory activity.
AB  - Single agents against multiple drug targets are highly topical. Hormone-dependent
      breast cancer (HDBC) may be more effectively treated by dual inhibition of
      aromatase and steroid sulfatase (STS), and several dual aromatase-sulfatase
      inhibitors (DASIs) have been recently reported. The best compounds from two
      leading classes of DASI, 3 and 9, are low nanomolar inhibitors. In search of a
      novel class of DASI, core motifs of two leading classes were combined to give a
      series of hybrid structures, with several compounds showing markedly improved
      dual inhibitory activities in the picomolar range in JEG-3 cells. Thus, DASIs 14
      (IC50: aromatase, 15 pM; STS, 830 pM) and 15 (IC50: aromatase, 18 pM; STS, 130
      pM) are the first examples of an exceptional new class of highly potent dual
      inhibitor that should encourage further development toward multitargeted
      therapeutic intervention in HDBC. 

PMID- 24900303
TI  - Extracting SAR Information from a Large Collection of Anti-Malarial Screening
      Hits by NSG-SPT Analysis.
AB  - We combine two graphical SAR analysis methods, Network-like Similarity Graphs
      (NSGs) and Similarity-Potency Trees (SPTs), to search for SAR information in a
      large and heterogeneous compound data set containing more than 13,000
      antimalarial screening hits that was recently released by GlaxoSmithKline (GSK).
      The NSG-SPT approach first identifies subsets of compounds inducing local SAR
      discontinuity in data sets and then extracts available SAR information from these
      subsets in a graphically intuitive manner. Applying the NSG-SPT analysis scheme,
      we have identified in the GSK collection compound subsets of high local SAR
      information content including both known and previously unknown antimalarial
      chemotypes, which yielded interpretable SAR patterns. This information should be
      helpful to prioritize and select antimalarial candidate compounds for further
      chemical exploration. Furthermore, the NSG-SPT tools are publicly available, and
      our study also shows how to practically apply these SAR analysis methods to study
      large compound data sets. 

PMID- 24900304
TI  - Discovery of MK-1220: A Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A
      Protease with Improved Preclinical Plasma Exposure.
AB  - The discovery of MK-1220 is reported along with the development of a series of
      HCV NS3/4A protease inhibitors containing a P2 to P4 macrocyclic constraint with
      improved preclinical pharmacokinetics. Optimization of the P2 heterocycle
      substitution pattern as well as the P3 amino acid led to compounds with greatly
      improved plasma exposure following oral dosing in both rats and dogs while
      maintaining excellent enzyme potency and cellular activity. These studies led to
      the identification of MK-1220. 

PMID- 24900305
TI  - Structure guided development of potent reversibly binding penicillin binding
      protein inhibitors.
AB  - Following from the evaluation of different types of electrophiles, combined
      modeling and crystallographic analyses are used to generate potent boronic acid
      based inhibitors of a penicillin binding protein. The results suggest that a
      structurally informed approach to penicillin binding protein inhibition will be
      useful for the development of both improved reversibly binding inhibitors,
      including boronic acids, and acylating inhibitors, such as beta-lactams. 

PMID- 24900306
TI  - Inhibitors of HCV NS5A: From Iminothiazolidinones to Symmetrical Stilbenes.
AB  - The iminothiazolidinone BMS-858 (2) was identified as a specific inhibitor of HCV
      replication in a genotype 1b replicon assay via a high-throughput screening
      campaign. A more potent analogue, BMS-824 (18), was used in resistance mapping
      studies, which revealed that inhibitory activity was related to disrupting the
      function of the HCV nonstructural protein 5A. Despite the development of coherent
      and interpretable SAR, it was subsequently discovered that in DMSO 18 underwent
      an oxidation and structural rearrangement to afford the thiohydantoin 47, a
      compound with reduced HCV inhibitory activity. However, HPLC bioassay
      fractionation studies performed after incubation of 18 in assay media led to the
      identification of fractions containing a dimeric species 48 that exhibited potent
      antiviral activity. Excision of the key elements hypothesized to be responsible
      for antiviral activity based on SAR observations reduced 48 to a simplified,
      symmetrical, pharmacophore realized most effectively with the stilbene 55, a
      compound that demonstrated potent inhibition of HCV in a genotype 1b replicon
      with an EC50 = 86 pM. 

PMID- 24900308
TI  - Membrane-targeted nanotherapy with hybrid liposomes for tumor cells leading to
      apoptosis.
AB  - Hybrid liposomes are nanosized liposomal particles and can be prepared by
      sonication of vesicular and micellar molecules in a buffer solution. In this
      study, we obtained the first successful experiment resulting in a good
      correlation between inhibitory effects of hybrid liposomes on the growth of
      various tumor cells and the membrane fluidity of tumor cells (plasma membranes).
      The results indicated that hybrid liposomes could provide the possibility of
      novel membrane-targeted nanotherapy for intractable cancers. 

PMID- 24900309
TI  - Hydrophobic Binding Hot Spots of Bcl-xL Protein-Protein Interfaces by Cosolvent
      Molecular Dynamics Simulation.
AB  - Identifying binding hot spots in protein-protein interfaces is important for
      understanding the binding specificity and for the design of nonpeptide, small
      molecule inhibitors. Molecular dynamics simulation in the isopropanol/water
      cosolvent environment and in water was employed to investigate Bcl-xL protein,
      which has a highly flexible, large, and primarily hydrophobic binding site.
      Simulations of either the apo- or holocrystal structures of the Bcl-xL in pure
      water fail to generate conformations found in the cocrystal structures of Bcl-xL
      in complex with its binding partners due to hydrophobic collapse. In contrast,
      simulations in cosolvent starting either from the apo- or holocrystal structure
      of the Bcl-xL yield binding-site conformations similar to that found in the
      cocrystal structures of Bcl-xL. Hydrophobic binding hot spots identified using
      the conformations from the cosolvent simulations are in excellent agreement with
      experimental structural data of known inhibitors. Importantly, cosolvent
      simulations revealed the highly dynamic nature of the hydrophobic binding pockets
      in Bcl-xL and yielded new structural insights for the design of novel Bcl-xL
      small-molecule inhibitors. 

PMID- 24900310
TI  - Homology Model Versus X-ray Structure in Receptor-based Drug Design: A
      Retrospective Analysis with the Dopamine D3 Receptor.
AB  - Structure-based design methods commonly used in medicinal chemistry rely on a
      three-dimensional representation of the receptor. However, few crystal structures
      are solved in comparison with the huge number of pharmaceutical targets. This
      often renders homology models the only information available. It is particularly
      true for G protein-coupled receptors (GPCRs), one of the most important targets
      for approved medicines and current drug discovery projects. However, very few
      studies have tested their validity in comparison with corresponding crystal
      structures, especially in a lead optimization perspective. The recent solving of
      dopamine D3 receptor crystal structure allowed us to assess our historical
      homology model. We performed a statistical analysis, by docking our in-house lead
      optimization library of 1500 molecules. We demonstrate here that the refined
      homology model suits at least as well as the X-ray structure. It is concluded
      that when the crystal structure of a given GPCR is not available, homology
      modeling can be an excellent surrogate to support drug discovery efforts. 

PMID- 24900311
TI  - Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor
      139.
AB  - GPR139 is an orphan G-protein coupled receptor (GPCR) which is primarily
      expressed in the central nervous system (CNS). In order to explore the biological
      function of this receptor, selective tool compounds are required. A screening
      campaign identified compound 1a as a high potency GPR139 agonist with an EC50 =
      39 nM in a calcium mobilization assay in CHO-K1 cells stably expressing the
      GPR139 receptor. In the absence of a known endogenous ligand, the maximum effect
      was set as 100% for 1a. Screening against 90 diverse targets revealed no cross
      reactivity issues. Assessment of the pharmacokinetic properties showed limited
      utility as in vivo tool compound in rat with a poor whole brain exposure of 61
      ng/g and a brain/plasma (b/p) ratio of 0.03. Attempts to identify a more suitable
      analogue identified the des-nitrogen analogue 1s with a reduced polar surface
      area of 76.7 A(2) and an improved b/p ratio of 2.8. The whole brain exposure
      remained low at 95 ng/g due to a low plasma exposure. 

PMID- 24900312
TI  - Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057
      DMSO Solvate).
AB  - Inhibition of mitogen-activated protein kinase/extracellular signal-regulated
      kinase kinase (MEK) represents a promising strategy for the discovery of a new
      generation of anticancer chemotherapeutics. Our synthetic efforts, beginning from
      the lead compound 2, were directed at improving antiproliferative activity
      against cancer cells as well as various drug properties. These efforts led to the
      discovery of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl
      2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide
      dimethylsulfoxide solvate (GSK1120212, JTP-74057 DMSO solvate; 1), a selective
      and highly potent MEK inhibitor with improved drug properties. We further
      confirmed that the antiproliferative activity correlates with cellular MEK
      inhibition and observed significant antitumor activity with daily oral dosing of
      1 in a tumor xenograft model. These qualities led to the selection of 1 for
      clinical development. 

PMID- 24900313
TI  - Discovery of AMG 853, a CRTH2 and DP Dual Antagonist.
AB  - Prostaglandin D2 (PGD2) plays a key role in mediating allergic reactions seen in
      asthma, allergic rhinitis, and atopic dermatitis. PGD2 exerts its activity
      through two G protein-coupled receptors (GPCRs), prostanoid D receptor (DP or
      DP1), and chemoattractant receptor-homologous molecule expressed on Th2 cells
      (CRTH2 or DP2). We report the optimization of a series of phenylacetic acid
      derivatives in an effort to improve the dual activity of AMG 009 against DP and
      CRTH2. These efforts led to the discovery of AMG 853 (2-(4-(4-(tert
      butylcarbamoyl)-2-(2-chloro-4-cyclopropylphenyl sulfonamido)phenoxy)-5-chloro-2
      fluorophenyl)acetic acid), which is being evaluated in human clinical trials for
      asthma. 

PMID- 24900314
TI  - Discovery of 4''-ether linked azithromycin-quinolone hybrid series: influence of
      the central linker on the antibacterial activity.
AB  - A series of novel C-4''-substituted azithromycins was synthesized and evaluated
      for in vitro antibacterial activity against a panel of representative
      erythromycin-susceptible and macrolide-lincosamide-streptogramin (MLS) resistant
      pathogens. In summary, azithromycin and quinolone substructures merged in a
      mutually SAR-compatible design gave rise to a new class of antimicrobials with an
      improved spectrum and potency over azithromycin. Prototypical analogues 7f and 8f
      display an improved potency versus azithromycin against Gram-positive and
      fastidious Gram-negative pathogens. In particular, these new leads maintain
      activity against MLS-resistant strains of Streptococcus pneumoniae and
      Streptococcus pyogenes. In addition, they represent an improvement over
      telithromycin (1) and cethromycin (2) against the fastidious Gram-negative
      pathogen Haemophilus influenzae. 

PMID- 24900315
TI  - Pyrazolopyridine Inhibitors of B-Raf(V600E). Part 1: The Development of
      Selective, Orally Bioavailable, and Efficacious Inhibitors.
AB  - The V600E mutation of B-Raf kinase results in constitutive activation of the MAPK
      signaling pathway and is present in approximately 7% of all cancers. Using
      structure-based design, a novel series of pyrazolopyridine inhibitors of B
      Raf(V600E) was developed. Optimization led to the identification of 3-methoxy
      pyrazolopyridines 17 and 19, potent, selective, and orally bioavailable agents
      that inhibited tumor growth in a mouse xenograft model driven by B-Raf(V600E)
      with no effect on body weight. On the basis of their in vivo efficacy and
      preliminary safety profiles, 17 and 19 were selected for further preclinical
      evaluation. 

PMID- 24900316
TI  - Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro
      drugs Activated by Cathepsin B.
AB  - Novel colchicine derivatives possessing various substituents at the C4 position
      were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher
      activity against cancer cell lines (A549, HT29, HCT116) as well as on mice
      transplanted with the HCT116 human colorectal carcinoma cell line than colchicine
      (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs
      having a dipeptide side chain and demonstrated that these pro-drugs were
      activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited
      selective toxicity to the tumor cells. 

PMID- 24900317
TI  - Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug
      Resistant Cells without Cox Inhibitory Activity.
AB  - Conformationally restricted indomethacin analogues were designed and prepared
      from the corresponding 2-substituted indoles, which were synthesized by a one-pot
      isomerization/enamide-ene metathesis as the key reaction. Conformational analysis
      by calculations, NMR studies, and X-ray crystallography suggested that these
      analogues were conformationally restricted in the s-cis or the s-trans form due
      to the 2-substituent as expected. Their biological activities on cyclooxygenase-1
      (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, and modulation of MRP-1
      mediated multidrug resistance (MDR) are described. Some of these indomethacin
      analogues enhanced doxorubicin cytotoxicity, although they do not have any COX
      inhibitory activity, which suggests that the MDR-modulating effect of an NSAID
      can be unassociated with its COX-inhibitory activity. This may be an entry into
      the combination chemotherapy of doxorubicin with a MDR modulator. 

PMID- 24900318
TI  - Discovery of CS-0777: A Potent, Selective, and Orally Active S1P1 Agonist.
AB  - CS-0777 (3) is phosphorylated in vivo, and the phosphate of CS-0777 (CS-0777-P)
      (4) acts as a selective S1P receptor-1 (S1P1) modulator. We report herein the
      synthesis of CS-0777 and CS-0777-P, pharmacological effects such as S1P1 and S1P3
      agonist activity in vitro, peripheral blood lymphocyte lowering effects and the
      suppressive effect on experimental autoimmune encephalomyelitis (EAE), and also
      the pharmacokinetics in rats. CS-0777-P had ~320-fold greater agonist activity
      for human S1P1 (EC50; 1.1 nM) relative to S1P3 (EC50; 350 nM). Following
      administration of single oral doses of 0.1 and 1 mg/kg of CS-0777 in rats,
      lymphocyte counts decreased significantly, with a nadir at 12 h postdose and
      recovery to vehicle control levels by 5 days postdose. In the EAE model compared
      to the vehicle-treated group, significant decreases in the cumulative EAE scores
      were observed for the 0.1 and 1 mg/kg CS-0777 groups in rats. CS-0777 is
      currently in clinical trials for the treatment of multiple sclerosis (MS). 

PMID- 24900319
TI  - Preparation, gram-negative antibacterial activity, and hydrolytic stability of
      novel siderophore-conjugated monocarbam diols.
AB  - A novel series of monocarbam compounds exhibiting promising antibacterial
      activity against multidrug resistant Gram-negative microorganisms is reported,
      along with the synthesis of one such molecule MC-1 (1). Also reported are
      structure-activity relationships associated with the in vitro and in vivo
      efficacy of 1 and related analogues in addition to the hydrolytic stability of
      such compounds and possible implications thereof. 

PMID- 24900320
TI  - Discovery of s-nitrosoglutathione reductase inhibitors: potential agents for the
      treatment of asthma and other inflammatory diseases.
AB  - S-Nitrosoglutathione reductase (GSNOR) regulates S-nitrosothiols (SNOs) and
      nitric oxide (NO) in vivo through catabolism of S-nitrosoglutathione (GSNO).
      GSNOR and the anti-inflammatory and smooth muscle relaxant activities of SNOs,
      GSNO, and NO play significant roles in pulmonary, cardiovascular, and
      gastrointestinal function. In GSNOR knockout mice, basal airway tone is reduced
      and the response to challenge with bronchoconstrictors or airway allergens is
      attenuated. Consequently, GSNOR has emerged as an attractive therapeutic target
      for several clinically important human diseases. As such, small molecule
      inhibitors of GSNOR were developed. These GSNOR inhibitors were potent,
      selective, and efficacious in animal models of inflammatory disease characterized
      by reduced levels of GSNO and bioavailable NO. N6022, a potent and reversible
      GSNOR inhibitor, reduced bronchoconstriction and pulmonary inflammation in a
      mouse model of asthma and demonstrated an acceptable safety profile. N6022 is
      currently in clinical development as a potential agent for the treatment of acute
      asthma. 

PMID- 24900321
TI  - Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor
      of DGAT-1.
AB  - Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final committed
      step in the biosynthesis of triglycerides. DGAT-1 knockout mice have been shown
      to be resistant to diet-induced obesity and have increased insulin sensitivity.
      Thus, inhibition of DGAT-1 may represent an attractive target for the treatment
      of obesity or type II diabetes. Herein, we report the discovery and
      characterization of a potent and selective DGAT-1 inhibitor PF-04620110 (3).
      Compound 3 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity
      versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1
      inhibition has been demonstrated through reduction of plasma triglyceride levels
      in rodents at doses of >=0.1 mg/kg following a lipid challenge. On the basis of
      this pharmacologic and pharmacokinetic profile, compound 3 has been advanced to
      human clinical studies. 

PMID- 24900322
TI  - The Implication of the First Agonist Bound Activated GPCR X-ray Structure on GPCR
      in Silico Modeling.
AB  - The very recently published first X-ray structure of the beta2 adrenergic
      receptor in its active state hosting a small molecule (PDB ID: 3P0G) reveals a
      lot of information about the G-protein-coupled receptor (GPCR) activation process
      from a structural point of view. When compared to the inactive state crystal
      structure of beta2, large differences are seen in the GPCR helical structure at
      the cytoplasmatic side, whereas very subtle changes occur at the ligand binding
      site. The observation that there are hardly any differences in the binding site
      of agonists and inverse agonists implies that in silico predictions of the
      efficacy of ligands will be very hard. This is illustrated by the example of an
      already published binding mode of a beta2 agonist, which has been modeled into
      the inactive state X-ray structure of the beta2 receptor. When comparing the
      modeled structure to the new activated X-ray structure, quantitative agreement of
      the binding mode is found, implying that the subtle changes between agonist
      binding to the activated state and inverse agonist binding to the inactive state
      can currently not be captured by standard in silico modeling methods. 

PMID- 24900323
TI  - Peptide-chlorambucil conjugates combat pgp-dependent drug efflux.
AB  - Cancer drugs, such as the ovarian cancer drug adriamycin, are effective at
      slowing disease progression and improving remission rates in patients. However,
      drug resistance often arises, limiting the activity of these agents in some
      patients. In particular, efflux pumps, which export drugs out of cells, limit the
      efficacy of a variety of anticancer agents. While inhibitors to block these pumps
      currently exist, they are usually not used clinically because they alter other
      drug properties. Here, we report a novel inhibitor of drug efflux that only
      reduces pump activity temporarily. This decreases the risk that it will alter
      drug function and cause nonspecific toxicity. P-glycoprotein efflux pumps are
      commonly overexpressed by malignant cells and are a major contributing factor to
      the development of drug resistance. Many therapeutics containing basic nitrogens,
      hydrophobic character, or aromaticity are efficiently eliminated from cells, and
      Pgp inhibitors must often be coadministered to limit this process. However,
      currently available inhibitors often alter the pharmacokinetic profiles of
      therapeutics or increase off-target toxicity, limiting their clinical utility.
      Here, we report the development of a novel panel of peptide-chlorambucil
      conjugates capable of efficiently decreasing efflux of Pgp substrates. These
      conjugates selectively improve adriamycin toxicity and uptake for short, but not
      prolonged, periods reducing the risk of altered pharmacokinetics and off-target
      effects. 

PMID- 24900324
TI  - Discovery of substituted biphenyl oxazolidinone inhibitors of cholesteryl ester
      transfer protein.
AB  - Recently, there has been a strong interest in the ability to increase levels of
      high density lipoprotein-cholesterol (HDL-C). This interest stems from the
      hypothesis that such an elevation in HDL-C will decrease the likelihood of
      cardiovascular disease. Inhibition of cholesteryl ester transfer protein (CETP)
      has been shown to elevate HDL-C levels in human subjects. This letter describes
      the discovery of a novel and potent (<100 nM IC50 for the inhibition of CE
      transfer) CETP inhibitor scaffold containing an oxazolidinone core. 

PMID- 24900325
TI  - Bisdionin C-a rationally designed, submicromolar inhibitor of family 18
      chitinases.
AB  - Chitinases of the GH18 family play important roles in a variety of pathogenic
      organisms and have also been shown to be involved in human asthma progression,
      making these enzymes potential drug targets. While a number of potent GH18
      chitinase inhibitors have been described, in general, these compounds suffer from
      limited synthetic accessibility or unfavorable medicinal-chemical properties,
      making them poor starting points for the development of chitinase-targeted drugs.
      Exploiting available structural data, we have rationally designed bisdionin C, a
      submicromolar inhibitor of GH18 enzymes, that possesses desirable druglike
      properties and tractable chemical synthesis. A crystallographic structure of a
      chitinase-bisdionin C complex shows the two aromatic systems of the ligand
      interacting with two conserved tryptophan residues exposed in the active site
      cleft of the enzyme, while at the same time forming extensive hydrogen-bonding
      interactions with the catalytic machinery. The observed mode of binding, together
      with inhibition data, suggests that bisdionin C presents an attractive starting
      point for the development of specific inhibitors of bacterial-type, but not plant
      type, GH 18 chitinases. 

PMID- 24900326
TI  - Thermodynamics of ligand binding and efficiency.
AB  - Analysis of the experimental binding thermodynamics for approximately 100 protein
      ligand complexes provides important insights into the factors governing ligand
      affinity and efficiency. The commonly accepted correlation between enthalpy and 
      TDeltaS is clearly observed for this relatively diverse data set. It is also
      clear that affinity (i.e., DeltaG) is not generally correlated to either enthalpy
      or -TDeltaS. This is a worrisome trend since the vast majority of computational
      structure-based design is carried out using interaction energies for one, or at
      most a few, ligand poses. As such, these energies are most closely comparable to
      enthalpies not free energies. Closer inspection of the data shows that in a few
      cases the enthalpy (or -TDeltaS) is correlated with free energy. It is tempting
      to speculate that this could be an important consideration as to why some targets
      are readily amenable to modeling and others are not. Additionally, analysis of
      the enthalpy and -TDeltaS efficiencies shows that the trends observed for ligand
      efficiencies with respect to molecular size are primarily a consequence of
      enthalpic, not entropic, effects. 

PMID- 24900327
TI  - Novel synthesis and biological evaluation of enigmols as therapeutic agents for
      treating prostate cancer.
AB  - Enigmol is a synthetic, orally active 1-deoxysphingoid base analogue that has
      demonstrated promising activity against prostate cancer. In these studies, the
      pharmacologic roles of stereochemistry and N-methylation in the structure of
      enigmols were examined. A novel enantioselective synthesis of all four possible
      2S-diastereoisomers of enigmol (2-aminooctadecane-3,5-diols) from l-alanine is
      reported, which features a Liebeskind-Srogl cross-coupling reaction between l
      alanine thiol ester and (E)-pentadec-1-enylboronic acid as the key step. In vitro
      biological evaluation of the four enigmol diastereoisomers and 2S,3S,5S-N
      methylenigmol against two prostate cancer cell lines (PC-3 and LNCaP) indicates
      that all but one diastereomer demonstrate potent oncolytic activity. In nude
      mouse xenograft models of human prostate cancer, enigmol was equally effective as
      standard prostate cancer therapies (androgen deprivation or docetaxel), and two
      of the enigmol diastereomers, 2S,3S,5R-enigmol and 2S,3R,5S-enigmol, also caused
      statistically significant inhibition of tumor growth. A pharmacokinetic profile
      of enigmol and N-methylenigmol is also presented. 

PMID- 24900328
TI  - Discovery of a Selective S1P1 Receptor Agonist Efficacious at Low Oral Dose and
      Devoid of Effects on Heart Rate.
AB  - Gilenya (fingolimod, FTY720) was recently approved by the U.S. FDA for the
      treatment of patients with remitting relapsing multiple sclerosis (RRMS). It is a
      potent agonist of four of the five sphingosine 1-phosphate (S1P) G-protein
      coupled receptors (S1P1 and S1P3-5). It has been postulated that fingolimod's
      efficacy is due to S1P1 agonism, while its cardiovascular side effects (transient
      bradycardia and hypertension) are due to S1P3 agonism. We have discovered a
      series of selective S1P1 agonists, which includes 3-[6-(5-{3-cyano-4-[(1
      methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)
      isoquinolinyl]propanoate, 20, a potent, S1P3-sparing, orally active S1P1 agonist.
      Compound 20 is as efficacious as fingolimod in a collagen-induced arthritis model
      and shows excellent pharmacokinetic properties preclinically. Importantly, the
      selectivity of 20 against S1P3 is responsible for an absence of cardiovascular
      signal in telemetered rats, even at high dose levels. 

PMID- 24900329
TI  - Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2
      Antagonist.
AB  - We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2)
      antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte
      chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of
      chemotaxis activity, an IC50 of 84 MUM in inhibition of the hERG potassium
      current, a free fraction of 58% in protein binding, high selectivity over other
      chemokine receptors and G-protein-coupled receptors, and acceptable oral
      bioavailability in rodents and primates. In human clinical trials, INCB3284
      exhibited a pharmacokinetic profile suitable for once-a-day dosing (T 1/2 = 15
      h). 

PMID- 24900330
TI  - The impact of ionization States of matrix metalloproteinase inhibitors on docking
      based inhibitor design.
AB  - The influence of ionization states of hydroxamates and retrohydroxamates and the
      presence of zinc ions in the active site were investigated using the wild-type
      and E402Q mutant of MMP-9. The deprotonated hydroxamates showed a significantly
      enhanced enrichment factor in the presence of zinc ions. A pharmacophore model
      was developed based on the deprotonated compounds and was used to identify four
      structurally diverse compounds with antiproliferative activities. 

PMID- 24900331
TI  - Disubstituted Bis-THF Moieties as New P2 Ligands in Nonpeptidal HIV-1 Protease
      Inhibitors.
AB  - A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand
      have been synthesized and evaluated. High affinity protease inhibitors (PIs) with
      an interesting activity on wild-type HIV and a panel of multi-PI resistant HIV-1
      mutants containing clinically observed, primary mutations were identified using a
      cell-based assay. A number of PIs have been synthesized that show equivalent and
      greater activity for HIV-1 mutant strains as compared to wild-type HIV-1. The
      activity on the purified enzyme was confirmed for a selection of analogues. 

PMID- 24900332
TI  - Discovery of a Potent Pyrazolopyridine Series of gamma-Secretase Modulators.
AB  - The synthesis and structure-activity relationship of a novel series of
      pyrazolopyridines are reported. These compounds represent a new class of gamma
      secretase modulators that demonstrate good in vitro potency in inhibiting Abeta42
      production. Examples with statistically significant in vivo efficacy in reducing
      the production of rat cerebrospinal fluid Abeta42 were also identified. 

PMID- 24900333
TI  - Potent CXCR4 antagonists containing amidine type Peptide bond isosteres.
AB  - A series of FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] analogues containing amidine
      type peptide bond isosteres were synthesized as selective CXC chemokine receptor
      type 4 (CXCR4) antagonists. An isosteric amidine substructure was constructed by
      a macrocyclization process using nitrile oxide-mediated C-N bond formation. All
      of the amidine-containing FC131 analogues exhibited potent SDF-1 binding
      inhibition to CXCR4. The Nal-Gly-substituted analogue was characterized as one of
      the most potent cyclic pentapeptide-based CXCR4 antagonists reported to date. The
      improved activity against human immunodeficiency virus (HIV) type-1 X4 strains
      suggested that addition of another basic amidine group to the peptide backbone
      effectively increases the selective binding of the peptides to CXCR4 receptor. 

PMID- 24900334
TI  - N-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the
      Treatment of Epilepsy.
AB  - A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were
      identified and found to be active in animal models of epilepsy and pain. The best
      compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an
      EC50 of 0.38 MUM and is selective for KCNQ2/Q3 channels. This compound was active
      in several rodent models of epilepsy and pain but upon repeated dosing had a
      number of unacceptable toxicities that prevented further development. On the
      basis of the structure-activity relationships developed around 12, a second
      compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro-benzamide, ICA-069673],
      was prepared and advanced into a phase 1 clinical study. Herein, we describe the
      structure-activity relationships that led to the identification of compound 12
      and to the corresponding pyrimidine 51. 

PMID- 24900335
TI  - Ranking high affinity ligands of low solubility by NMR spectroscopy.
AB  - Cyclosporine A (CsA) and its chemical analogues EthVal4Cs, MeVal4Cs, and Me(d
      Ala)3EthVal4Cs (Alisporivir) all interact with cyclophilin A (CypA). The latter
      Alisporivir is a nonimmunosuppressive CsA derivative that has potent anti-HCV
      properties in clinical trials. We show here that NMR spectroscopy can be used to
      rank this series of related pharmacological molecules despite their high affinity
      for the target protein and low solubility in water. The novel method is based on
      the possibility to detect distinct NMR signals from the different protein
      complexes in a mixture. The method has enabled us to distinguish subtle effects
      of discrete chemical modifications of the parent molecule on the affinity of the
      ligands for the target protein. 

PMID- 24900336
TI  - Target Flexibility in RNA-Ligand Docking Modeled by Elastic Potential Grids.
AB  - The highly flexible nature of RNA provides a formidable challenge for structure
      based drug design approaches that target RNA. We introduce an approach for
      modeling target conformational changes in RNA-ligand docking based on potential
      grids that are represented as elastic bodies using Navier's equation. This
      representation provides an accurate and efficient description of RNA-ligand
      interactions even in the case of a moving RNA structure. When applied to a data
      set of 17 RNA-ligand complexes, filtered out of the largest validation data set
      used for RNA-ligand docking so far, the approach is twice as successful as
      docking into an apo structure and still half as successful as redocking to the
      holo structure. The approach allows considering RNA movements of up to 6 A rmsd
      and is based on a uniform and robust parametrization of the properties of the
      elastic potential grids, so that the approach is applicable to different RNA
      ligand complex classes. 

PMID- 24900337
TI  - Nitric oxide donor doxorubicins accumulate into Doxorubicin-resistant human colon
      cancer cells inducing cytotoxicity.
AB  - Products 4 and 5, obtained by conjugation of doxorubicin with nitric oxide (NO)
      donor nitrooxy and phenylsulfonyl furoxan moieties, respectively, accumulate in
      doxorubicin-resistant human colon cancer cells (HT29-dx), inducing high
      cytotoxicity. This behavior parallels the ability of the compounds to generate
      NO, detected as nitrite, in these cells. Preliminary immunoblotting studies
      suggest that the mechanism that underlies the cytotoxic effect could involve
      inhibition of cellular drug efflux due to nitration of tyrosine residues of the
      MRP3 protein pump. 

PMID- 24900338
TI  - Synthesis and Evaluation of 5-Fluoro-2-aryloxazolo[5,4-b]pyridines as beta
      Amyloid PET Ligands and Identification of MK-3328.
AB  - 5-Fluoro-2-aryloxazolo[5,4-b]pyridines were synthesized and investigated as
      potential (18)F containing beta-amyloid PET ligands. In competition binding
      assays using human AD brain homogenates, compounds 14b, 16b, and 17b were
      identified as having favorable potency versus human beta-amyloid plaque and were
      radiolabeled for further evaluation in in vitro binding and in vivo PET imaging
      experiments. These studies led to the identification of 17b (MK-3328) as a
      candidate PET ligand for the clinical assessment of beta-amyloid plaque load. 

PMID- 24900339
TI  - Novel alkynylphosphonate analogue of calcitriol with potent antiproliferative
      effects in cancer cells and lack of calcemic activity.
AB  - Here, we describe the design and synthesis of diethyl [(5Z,7E)-(1S,3R)-1,3
      dihydroxy-9,10-secochola-5,7,10(19)-trien-23-in-24-yl] phosphonate (compound 10),
      which combines the low calcemic properties of phosphonates with the decreased
      metabolic inactivation due to the presence of a triple bond in C-24 and studied
      its in vitro effects on several cancer cell lines and its in vivo effects on
      blood calcium levels. We demonstrate that this compound is a potent
      antiproliferative vitamin D analogue, showing lack of calcemic effects in vivo. 

PMID- 24900340
TI  - N-Methylated sst2 Selective Somatostatin Cyclic Peptide Analogue as a Potent
      Candidate for Treating Neurogenic Inflammation.
AB  - A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin
      analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected
      observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF
      ) with a potent inhibitory action on sensory neuropeptide release in vitro and on
      acute neurogenic inflammatory response in vivo. The analogue shows selectivity
      toward somatostatin receptor subtype 2 (sst2). Extensive 2D NMR spectroscopy and
      molecular dynamics simulation revealed the solution conformation of the analogue,
      which can be adopted as a lead for the further structure-activity relationship
      studies targeting neurogenic inflammation. 

PMID- 24900341
TI  - Benzodiazepinone Derivatives as CRTH2 Antagonists.
AB  - Multiple CRTH2 antagonists are currently evaluated in human clinical trials for
      asthma and chronic obstructive pulmonary disease (COPD). During our lead
      optimization for CRTH2 antagonists, an observation of an intramolecular hydrogen
      bond in ortho-phenylsulfonamido benzophenone derivatives led to the design and
      synthesis of conformationally constrained benzodiazepinones as potent CRTH2
      antagonists. The benzodiazepinones are 2 orders of magnitude more potent than the
      original flexible bisaryl ethers in our binding assay. Selected
      benzodiazepinones, such as compound 6, were also potent in the human eosinophil
      shape change assay. Analysis of the rigid conformations of these
      benzodiazepinones and ortho-phenylsulfonamido benzophenones provided an
      explanation for the structure-activity relationship and revealed the possible
      bound conformations to CRTH2, which may be useful for building a pharmacophore
      model of CRTH2 antagonists. 

PMID- 24900342
TI  - Assessment of partially deoxygenated deoxynojirimycin derivatives as
      glucosylceramide synthase inhibitors.
AB  - Glucosylceramide synthase (GCS) is an approved drug target for the treatment of
      Gaucher disease and is considered as a valid target for combating other human
      pathologies, including type 2 diabetes. The clinical drug N-butyldeoxynojirimycin
      (Zavesca) is thought to inhibit through mimicry of its substrate, ceramide. In
      this work we demonstrate that, in contrast to what is proposed in this model, the
      C2-hydroxyl of the deoxynojirimycin core is important for GCS inhibition. Here we
      show that C6-OH appears of less important, which may set guidelines for the
      development of GCS inhibitors that have less affinity (in comparison with
      Zavesca) for other glycoprocessing enzymes, in particular those hydrolases that
      act on glucosylceramide. 

PMID- 24900343
TI  - Chemical transformations that yield compounds with distinct activity profiles.
AB  - We have systematically searched for chemical changes that generate compounds with
      distinct biological activity profiles. For this purpose, activity profiles were
      generated for ~42000 compounds active against human targets. Unique activity
      profiles involving multiple target proteins were determined, and all possible
      matched molecular pairs (MMPs) were identified for compounds representing these
      profiles. An MMP is defined as a pair of compounds that are distinguished from
      each other only at a single site such as an R group or ring system. For example,
      in an MMP, a hydroxyl group might be replaced by a halogen atom or a benzene ring
      by an amide group. From ~37500 MMPs, more than 300 nonredundant chemical
      transformations were isolated that yielded compounds with distinct activity
      profiles. None of these transformations was found in pairs of compounds with
      overlapping activity profiles. These transformations were ranked according to the
      number of MMPs, the number of activity profiles, and the total number of targets
      that they covered. In many instances, prioritized transformations involved ring
      systems of varying complexity. All transformations that were found to switch
      activity profiles are provided to enable further analysis and aid in compound
      design efforts. 

PMID- 24900344
TI  - Targeting anthracycline-resistant tumor cells with synthetic aloe-emodin
      glycosides.
AB  - The cytotoxic activity of aloe-emodin (AE), a natural anthranoid that readily
      permeates anthracycline-resistant tumor cells, was improved by the attachment of
      an amino-sugar unit to its anthraquinone core. The new class of AE glycosides
      (AEGs) showed a significant improvement in cytotoxicity-up to more than 2 orders
      of magnitude greater than those of AE and the clinically used anthracycline
      doxorubicin (DOX)-against several cancer cell lines with different levels of DOX
      resistance. Incubation with the synthetic AEGs induced cell death in less than
      one cell cycle, indicating that these compounds do not directly target the cell
      division mechanism. Confocal microscopy provided evidence that unlike DOX, AEGs
      accumulated in anthracycline-resistant tumor cells in which resistance is
      conferred by P-glycoprotein efflux pumps. The results of this study demonstrate
      that AEGs may serve as a promising scaffold for the development of cytotoxic
      agents capable of overcoming anthracycline resistance in tumor cells. 

PMID- 24900345
TI  - Structure-Activity Relationship Studies of HIV-1 Integrase Oligonucleotide
      Inhibitors.
AB  - Integration of human immunodeficiency virus type 1 DNA into an infected cell
      genome is one of the key steps of the viral replication cycle. Therefore, viral
      enzyme integrase, which realizes the integration, represents an attractive and
      validated target for the development of new antiviral drugs. In this paper, the
      anti-integrase activity of a series of conjugates of single-stranded
      oligonucleotides with hydrophobic molecules was tested, and the structure
      activity relationships were also analyzed. Both oligonucleotide and hydrophobic
      parts of the conjugates influenced the inhibitory potency. Conjugates of 11-mer
      phosphorothioate oligonucleotides with 6-carboxy-4,7,2',4',5',7'
      hexachlorofluorescein (HEX) were found to be the most efficient inhibitors (IC50
      = 20 nM) and might be considered as lead compounds for further development of
      integrase inhibitors. 

PMID- 24900346
TI  - Inhibitors of Ketohexokinase: Discovery of Pyrimidinopyrimidines with Specific
      Substitution that Complements the ATP-Binding Site.
AB  - Attenuation of fructose metabolism by the inhibition of ketohexokinase (KHK;
      fructokinase) should reduce body weight, free fatty acids, and triglycerides,
      thereby offering a novel approach to treat diabetes and obesity in response to
      modern diets. We have identified potent, selective inhibitors of human hepatic
      KHK within a series of pyrimidinopyrimidines (1). For example, 8, 38, and 47
      exhibited KHK IC50 values of 12, 7, and 8 nM, respectively, and also showed
      potent cellular KHK inhibition (IC50 < 500 nM), which relates to their intrinsic
      potency vs KHK and their ability to penetrate cells. X-ray cocrystal structures
      of KHK complexes of 3, 8, and 47 revealed the important interactions within the
      enzyme's adenosine 5'-triphosphate (ATP)-binding pocket. 

PMID- 24900347
TI  - The 3-Deoxy Analogue of alpha-GalCer: Disclosing the Role of the 4-Hydroxyl Group
      for CD1d-Mediated NKT Cell Activation.
AB  - KRN7000, or alpha-GalCer, is a potent agonist for natural killer T (NKT) cells.
      The 3-hydroxyl group of its phytosphingosine moiety is important for activating
      NKT cells, whereas its 4-hydroxyl group is perceived to be less crucial. To
      experimentally determine the role of the 4-hydroxyl group, we synthesized the 3
      deoxy analogue of alpha-GalCer. It was found that 3-deoxy-alpha-GalCer induced
      potent cytokine responses from NKT cells, comparable to those of both alpha
      GalCer and 4-deoxy-alpha-GalCer. This result and our docking studies suggest that
      the effects of an absence of the 3-hydroxyl group are compensated by the presence
      of a hydroxyl group at the C-4 position. Thus, we conclude that the 4-hydroxyl
      group of alpha-GalCer is as important to the mechanism of action as the 3
      hydroxyl group and that the two hydroxyl groups could play individual and
      cooperative roles in orienting the glycolipid into the proper position in CD1d to
      be recognized by the T cell receptor of NKT cells. 

PMID- 24900348
TI  - A Platform for the Detection of Trypanosomes via Selective Small Molecule
      Recognition.
AB  - Trypanothione (TSH2), a metabolite unique to trypanosomal parasites, was
      evaluated as a potential biomarker for trypanosomal infection using fluorescence
      as the means of detection. Fluoroescein arsenical helix binder (FLASH) was
      prepared and used to detect TSH2. Since it has low background fluorescence and
      forms a highly emissive complex with TSH2, it can be used to detect low
      micromolar concentrations of TSH2 in serum. The large dynamic range of FLASH and
      its selectivity for detection of the dithiol metabolite indicate that arsenical
      probes may offer a promising new platform for the diagnosis of trypanosomal
      infection. 

PMID- 24900349
TI  - Optimization of the First Selective Steroid-11beta-hydroxylase (CYP11B1)
      Inhibitors for the Treatment of Cortisol Dependent Diseases.
AB  - CYP11B1 is the key enzyme in cortisol biosynthesis, and its inhibition with
      selective compounds is a promising strategy for the treatment of diseases
      associated with elevated cortisol levels, such as Cushing's syndrome or metabolic
      disease. Expanding on a previous study from our group resulting in the first
      potent and rather selective inhibitor described so far (1, IC50 = 152 nM), we
      herein describe further optimizations of the imidazolylmethyl pyridine core. Five
      compounds among the 42 substances synthesized showed IC50 values below 50 nM.
      Most interesting was the naphth-1-yl compound 23 (IC50 = 42 nM), showing a 49
      fold selectivity toward the highly homologous CYP11B2 (1: 18-fold) as well as
      selectivity toward the androgen and estrogen forming enzymes CYP17 and CYP19,
      respectively. 

PMID- 24900350
TI  - Rigid Analogues of Antimitotic Indolobenzazepinones: New Insights into Tubulin
      Binding via Molecular Modeling.
AB  - Two rigid analogues of 5-ethylindolobenzazepinone 4, a potent cytotoxic agent and
      inhibitor of tubulin polymerization, were prepared. The first was the indane
      derivative 5, in which the ethyl group is attached to the benzo moiety. The
      second was the pyrrolidine analogue 6, in which the ethyl chain was bound to the
      lactam nitrogen. While both compounds were considerably less active inhibitors of
      KB cell growth as compared to 4, inhibition of tubulin polymerization was only
      moderately reduced. Tubulin docking studies indicated that the aR and aS
      atropoisomers of 5 and 6 occupy different binding pockets at the colchicine
      binding site. Conversely, both aS-5 and aS-6 occupy the same binding pocket as
      aSS-4 but do not benefit from the favorable hydrophobic interactions provided by
      the C5 alkyl group of 4, thus possibly explaining their lower activities. 

PMID- 24900351
TI  - Bivalent Ligands for the Serotonin 5-HT3 Receptor.
AB  - The serotonin 5-HT3 receptor is a ligand-gated ion channel, which by virtue of
      its pentameric architecture, can be considered to be an intriguing example of
      intrinsically multivalent biological receptors. This paper describes a general
      design approach to the study of multivalency in this multimeric ion channel.
      Bivalent ligands for 5-HT3 receptor have been designed by linking an
      arylpiperazine moiety to probes showing different functional features. Both
      homobivalent and heterobivalent ligands have shown 5-HT3 receptor affinity in the
      nanomolar range, providing evidence for the viability of our design approach.
      Moreover, the high affinity shown by homobivalent ligands suggests that bivalency
      is a promising approach in 5-HT3 receptor modulation and provides the rational
      basis for applying the concepts of multivalency to the study of 5-HT3 receptor
      function. 

PMID- 24900352
TI  - Identification of NAE Inhibitors Exhibiting Potent Activity in Leukemia Cells:
      Exploring the Structural Determinants of NAE Specificity.
AB  - MLN4924 is a selective inhibitor of the NEDD8-activating enzyme (NAE) and has
      advanced into clinical trials for the treatment of both solid and hematological
      malignancies. In contrast, the structurally similar compound 1 (developed by
      Millennium: The Takeda Oncology Company) is a pan inhibitor of the E1 enzymes
      NAE, ubiquitin activating enzyme (UAE), and SUMO-activating enzyme (SAE) and is
      currently viewed as unsuitable for clinical use given its broad spectrum of E1
      inhibition. Here, we sought to understand the determinants of NAE selectivity. A
      series of compound 1 analogues were synthesized through iterative
      functionalization of the purine C6 position and evaluated for NAE specificity.
      Optimal NAE specificity was achieved through substitution with primary N-alkyl
      groups, while bulky or secondary N-alkyl substituents were poorly tolerated. When
      assessed in vitro, inhibitors reduced the growth and viability of malignant K562
      leukemia cells. Through this study, we have successfully identified a series of
      sub-10 nM NAE-specific inhibitors and thereby highlighted the functionalities
      that promote NAE selectivity. 

PMID- 24900353
TI  - Combination of a Beta adrenoceptor modulator and a norepinephrine-serotonin
      uptake inhibitor for the treatment of obesity.
AB  - We report the novel combination of a selective beta adrenoceptor modulator and a
      norepinephrine-serotonin uptake inhibitor (sibutramine) with potential for the
      treatment of obesity. The synthesis and characterization of 6-[4-[2-[[(2S)-3-(9H
      carbazol-4-yloxy)-2-hydroxypropyl]amino]-2-methylpropyl]phenoxy]pyridine-3
      carboxamide (LY377604), a human beta3-adrenergic receptor agonist and beta1- and
      beta2-adrenergic receptor antagonist with no sympathomimetic activity at the
      beta1- and beta2-adrenergic receptors, is reported. Some in vivo data in both
      rats and humans is presented. 

PMID- 24900354
TI  - Quantification of Interactions between Serum Albumin and Endogenous Free Fatty
      Acids or Exogenous Chemicals by Stable Isotope-Coded Mass Spectrometry.
AB  - As primary endogenous ligands of serum albumin, free fatty acids exert versatile
      effects on the albumin conformation through cooperative or competitive
      interactions with exogenous chemicals. Based on equilibrium partition between n
      hexane and aqueous phases, we have established three indexes, defined as R A, R
      V, and R T, for quantitative assessment of the intrinsic binding affinity, the
      affinitive variation induced by exogenous chemicals, and the topological
      dependence of albumin affinity, respectively. When albumin molecules in the
      aqueous phase are in native or denatured forms, or disturbed by exogenous
      chemicals, corresponding changes of free fatty acids in the n-hexane phase can be
      quantified by an iFFAM (isotope-coded free fatty acid methylation) approach. Free
      fatty acids from the control and the sample are differentially derived by d0- or
      d3-methanol and analyzed by gas chromatography-mass spectrometry. Changes of
      fatty acids can be revealed by peak ratios of d0- or d3-labeled fragment ions of
      fatty acid methyl esters. 

PMID- 24900355
TI  - Design and synthesis of benzenesulfonamide derivatives as potent anti-influenza
      hemagglutinin inhibitors.
AB  - Structural optimization of salicylamide-based hemagglutinin (HA) inhibitor 1
      resulted in the identification of cis-3-(5-hydroxy-1,3,3
      trimethylcyclohexylmethylamino)benzenesulfonamide 28 and its derivatives as
      potent anti-influenza agents. The lead compound 28 and its 2-chloro analogue 40
      can effectively prevent cytopathic effects (CPE) caused by infection of influenza
      A/Weiss/43 strain (H1N1) with EC50 values of 210 and 86 nM, respectively.
      Mechanism of action studies indicate that 40 and its analogues inhibit the virus
      fusion with host endosome membrane by binding to HA and stabilizing the prefusion
      HA structure. With significantly improved metabolic stability, the reported
      series represents the first generation of orally bioavailable HA inhibitors that
      have a good selectivity window and potential for further development as novel
      anti-influenza agents. 

PMID- 24900356
TI  - A Strategy for Suppressing Redox Stress within Mitochondria.
AB  - An aza analogue (1) of the experimental neuroprotective drug idebenone has been
      prepared and evaluated. The compound quenches lipid peroxidation more effectively
      than alpha-tocopherol and potently suppresses reactive oxygen species in cells
      under oxidative stress. It is thought to do so via a catalytic cycle in which
      both forms of oxidative stress are suppressed simultaneously. Consequently, the
      compound effectively protects cultured CEM leukemia cells and Friedreich's ataxia
      fibroblasts from oxidative stress more effectively than idebenone or idebenol. 

PMID- 24900357
TI  - The myo-1,2-Diaminocyclitol Scaffold Defines Potent Glucocerebrosidase Activators
      and Promising Pharmacological Chaperones for Gaucher Disease.
AB  - A series of cyclitol derivatives with myo-configuration are beta
      glucocerebrosidase (GCase) inhibitors and show excellent characteristics for the
      development of pharmacological chaperones for enzyme deficiency in Gaucher
      disease (GD). The most potent inhibitor, (1S,2R,3R,4S,5R,6S)-5,6
      bis(nonylamino)cyclohexane-1,2,3,4-tetraol, displayed a K i value of 26 nM in
      isolated enzyme and also inhibited GCase in wild-type (wt) human fibroblasts at
      nanomolar concentrations. This diaminocyclitol produced maximum increases of
      GCase activities of 60% in N370S lymphoblasts at 100 nM and 30% in L444P at 1 nM
      following a 3-day incubation, showing the permeability, subcellular distribution,
      and cell metabolism characteristics for use as pharmacological chaperone. 

PMID- 24900358
TI  - Discovery and Hit-to-Lead Optimization of Non-ATP Competitive MK2 (MAPKAPK2)
      Inhibitors.
AB  - A novel series of non-ATP-competitive MK2 inhibitors based on a furan-2
      carboxyamide scaffold was discovered through high-throughput screening using the
      affinity selection-mass spectrometry-based Automated Ligand Identification System
      platform. Medicinal chemistry efforts optimized the initial screening hit to
      leadlike compounds with significant improvements in biochemical and cellular
      potencies, while maintaining excellent kinase selectivity and in vitro
      pharmacokinetic properties. Biophysical and biochemical studies confirmed the
      unique non-ATP-competitive binding mode of this series and suggested that highly
      selective inhibitors of MK2 should be feasible by targeting the outside ATP
      pocket. 

PMID- 24900359
TI  - Optimization of the Central Core of Indolinone-Acetic Acid-Based CRTH2 (DP2)
      Receptor Antagonists.
AB  - New spiroindolinone antagonists of CRTH2 are described. Following identification
      of insufficient stability in human plasma as an important liability of the lead
      compounds, replacement of the spirosuccinimide core with a spirohydantoin or
      spiropyrrolidinone structure has yielded a compound that is fully stable in human
      plasma and with good potency in a human whole blood assay (IC50 = 69 nM) but
      shows a much lower oral bioavailability (6-9% in rodents) than the earlier
      compounds. Successive optimization aimed at restoring an acceptable oral
      bioavailability has yielded compound (S)-17a, which exhibits both stability in
      human plasma and a good oral bioavailability in rat (37%) and mouse (39%). This
      compound is also active in a mouse model of ovalbumin-induced lung inflammation
      following oral dosing at 30 mg/kg. 

PMID- 24900360
TI  - Synthesis and Cardiac Imaging of (18)F-Ligands Selective for beta1
      Adrenoreceptors.
AB  - A series of potent and selective beta1-adrenoreceptor ligands were identified
      (IC50 range, 0.04-0.25 nM; beta1/beta2 selectivity range, 65-450-fold), labeled
      with the PET radioisotope fluorine-18 and evaluated in normal Sprague-Dawley
      rats. Tissue distribution studies demonstrated uptake of each radiotracers from
      the blood pool into the myocardium (0.48-0.62% ID/g), lung (0.63-0.97% ID/g), and
      liver (1.03-1.14% ID/g). Dynamic MUPET imaging confirmed the in vivo dissection
      studies. 

PMID- 24900361
TI  - Exploring aigialomycin d and its analogues as protein kinase inhibitors for
      cancer targets.
AB  - The natural product aigialomycin D (1) is a member of the resorcylic acid lactone
      (RAL) family possessing protein kinase inhibitory activities. This paper
      describes the synthesis of aigialomycin D and a series of its analogues and their
      activity for the inhibition of protein kinases related to cancer pathways. A
      preliminary study of these compounds in the inhibition of CDK2/cyclin A kinase
      has found that aigialomycin D and analogues 11 and 23 are moderate CDK2/cyclin A
      inhibitors with IC50 values of ca. 20 MUM. Kinase profiling of aigialomycin D
      against a panel of kinases has led to the identification of MNK2 as a promising
      target (IC50 = 0.45 MUM), and preliminary structure-activity relationship studies
      have been carried out to identify the essential functional groups for activity. 

PMID- 24900363
TI  - Synthetic N-alkylated iminosugars as new potential immunosuppressive agents.
AB  - The new emerging immunosuppressive effects displayed by iminosugars have not been
      much investigated so far. Several new N-alkyl dideoxy iminoalditols were designed
      and synthesized to explore their immunosuppressive effects. These iminosugars
      inhibited the proliferation of mouse splenocytes and the secretion of both IFN
      gamma and IL-4, which are the hallmark cytokines of Th1 and Th2 cells,
      respectively. Some compounds exerted good inhibitory effects. More importantly,
      the synthetic iminosugars prolonged the allograft survival in the mouse skin
      transplantation experiment. Our results provide a lead for further elucidation of
      the structure-activity relationships and modifications of iminosugars for better
      immunosuppressive agents. 

PMID- 24900362
TI  - A Novel (18)F-Labeled Imidazo[2,1-b]benzothiazole (IBT) for High-Contrast PET
      Imaging of beta-Amyloid Plaques.
AB  - (18)F-labeled imidazo[2,1-b]benzothiazole ([(18)F]8) was synthesized and
      evaluated as a tracer for cerebral beta-amyloid deposits (Abeta) by means of
      positron emission tomography (PET). [(18)F]8 exhibits a high affinity to Abeta
      and suitable brain uptake kinetics combined with a high metabolic stability in
      the brain. In a double transgenic APP/PS1 mouse model of Alzheimer's disease, we
      demonstrated a specific uptake of [(18)F]8 in Abeta-containing telencephalic
      brain regions. The specific binding of [(18)F]8 to Abeta was confirmed by
      regional brain biodistribution and autoradiography and correlated to
      immunohistochemistry staining. Analysis of brain sections of APP/PS1 mouse
      injected with a cocktail of [(18)F]8 and reference compound [(3)H]PiB revealed
      that the two tracers bind to Abeta plaques in the brain of mouse in a comparable
      binding pattern. [(18)F]8 represents the first high-contrast PET imaging agent
      for detection of Abeta plaques in transgenic mouse model of Alzheimer's disease
      and holds promise for transfer to a clinical evaluation. 

PMID- 24900365
TI  - Nowhere to go but up: the return of medicinal chemistry.
AB  - Medicinal chemistry, as a field, has moved into new and unwelcome territory. How
      did we get here, and what might be the way out? 

PMID- 24900364
TI  - Optimization of Potent Inhibitors of P. falciparum Dihydroorotate Dehydrogenase
      for the Treatment of Malaria.
AB  - Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially
      represents a new treatment option for malaria, since DHODH catalyzes the rate
      limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable
      to salvage pyrimidines and must rely on de novo biosynthesis for survival. We
      report herein the synthesis and structure-activity relationship of a series of 5
      (2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent
      inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of
      efficacy observed in three mouse models of malaria, acceptable safety
      pharmacology risk assessment and safety toxicology profile in rodents, lack of
      potential drug-drug interactions, acceptable ADME/pharmacokinetic profile, and
      projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-N
      cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug
      development candidate. 

PMID- 24900366
TI  - Prodrugs of a CXC Chemokine-12 (CXCL12) Neutraligand Prevent Inflammatory
      Reactions in an Asthma Model in Vivo.
AB  - Chalcone 4 (compound 1) is a small molecule that neutralizes the CXC chemokine
      CXCL12 and prevents it from acting on the CXCR4 and CXCR7 receptors. To overcome
      its poor solubility in aqueous buffers, we designed highly soluble analogues of
      compound 1, phosphate, l-seryl, and sulfate, all inactive by themselves on CXCL12
      but when cleaved in vivo into 1, highly active locally at a low dose in a mouse
      airway hypereosinophilia model. 

PMID- 24900367
TI  - Proposed Bioactive Conformations of Opiorphin, an Endogenous Dual APN/NEP
      Inhibitor.
AB  - The conformational profiles for the endogenous peptide Opiorphin and a set of
      seven analogues exhibiting different inhibitory activities toward human
      aminopeptidase N (hAPN) and human neprilysin (hNEP) were independently computed
      to deduce a bioactive conformation that Opiorphin may adopt when binding these
      two enzymes. The conformational space was thoroughly sampled using an iterative
      simulated annealing protocol, and a library of low-energy conformers was
      generated for each peptide. Bioactive Opiorphin conformations fitting our
      experimental structure-activity relationship data were identified for hAPN and
      hNEP using computational pairwise comparisons between each of the unique low
      energy conformations of Opiorphin and its analogues. The obtained results provide
      a structural explanation for the dual hAPN and hNEP inhibitory activity of
      Opiorphin and show that the inborn flexibility of Opiorphin is essential for its
      analgesic activity. 

PMID- 24900368
TI  - 5-Arylbenzothiadiazine Type Compounds as Positive Allosteric Modulators of
      AMPA/Kainate Receptors.
AB  - The potential therapeutic benefit of compounds able to activate AMPA receptors
      (AMPAr) has led to the search for new AMPAr positive modulators. On the basis of
      crystallographic data of the benzothiadiazines binding mode in the S1S2 GluA2
      dimer interface, a set of 5-aryl-2,3-dihydrobenzothiadiazine type compounds has
      been synthesized and tested. Electrophysiological results suggested that 5
      heteroaryl substituents on the benzothiadiazine core like 3-furanyl and 3
      thiophenyl dramatically enhance the activity as positive modulators of AMPAr with
      respect to IDRA21 and cyclothiazide. Mouse brain microdialysis studies have
      suggested that 7-chloro-5-(3-furyl)-3-methyl-3,4-dihydro-2H-1,2,4
      benzothiadiazine 1,1-dioxide crosses the blood-brain barrier after
      intraperitoneal injection. Biological results have been rationalized by a
      computational docking simulation that it has currently employed to design new
      AMPAr-positive modulator candidates. 

PMID- 24900369
TI  - Sphingolipid analogues inhibit development of malaria parasites.
AB  - Plasmodium-infected erythrocytes have been shown to employ sphingolipids from
      both endogenous metabolism as well as existing host pools. Therapeutic agents
      that limit these supplies have thus emerged as intriguing, mechanistically
      distinct putative targets for the treatment of malaria infections. In an initial
      screen of our library of sphingolipid pathway modulators for efficacy against two
      strains of the predominant human malaria species Plasmodium falciparum and
      Plasmodium knowlesi, a series of orally available, 1-deoxysphingoid bases were
      found to possess promising in vitro antimalarial activity. To better understand
      the structural requirements that are necessary for this observed activity, a
      second series of modified analogues were prepared and evaluated. Initial
      pharmacokinetic assessments of key analogues were investigated to evaluate plasma
      and red blood cell concentrations in vivo. 

PMID- 24900370
TI  - Ring Structure and Aromatic Substituent Effects on the pK a of the Benzoxaborole
      Pharmacophore.
AB  - In this work, we present an investigation into the physical properties of a
      unique class of aromatic boronic acids, the benzoxaboroles. Using
      spectrophotometric methods, the ionization constants of a family of substituted
      benzoxaboroles are determined. Heterocyclic ring modifications are examined to
      determine their effects on the ionization of the boronic acid moiety. It is also
      shown that the substituent effects about the aromatic ring follow a Hammett
      relationship with the compounds' measured pK a values. Finally, these substituent
      effects are also shown to extend to the sugar binding properties of these
      compounds under physiologically relevant conditions. Combined, these data will
      inform medicinal chemists wishing to tailor the ionization and/or ability of this
      class of compound to bind diol-containing biomolecules. 

PMID- 24900371
TI  - (18)F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary
      tangles in Alzheimer's disease brains.
AB  - We synthesized and evaluated (E)-4-((6-(2-(2-(2
      fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline
      (FPPDB) as a probe for the imaging of neurofibrillary tangles (NFTs) in patients
      with Alzheimer's disease (AD). In assays using thioflavin S (ThS) as a
      competitive ligand, FPPDB competed with ThS well and showed high affinity for
      both tau and Abeta1-42 aggregates (K i = 13.0 and 20.0 nM, respectively). The
      results of saturation binding assays also verified that FPPDB bound to both tau
      and Abeta1-42 aggregates with high affinity (K d = 44.8 nM and B max = 45.8
      pmol/nmol protein for tau aggregates and K d = 45.4 nM and B max = 38.9 pmol/nmol
      protein for Abeta1-42 aggregates). Furthermore, [(18)F]FPPDB substantially
      labeled NFTs and senile plaques in AD brain sections but not control brain
      sections. In biodistribution experiments using normal mice, [(18)F]FPPDB
      displayed higher uptake (4.28% ID/g at 2 min postinjection) into and washout
      (2.53% ID/g at 60 min postinjection) from the brain with time. On the basis of
      the chemical structure of FPPDB, further increases in selective binding to tau
      aggregates may lead to the development of more useful probes for the imaging of
      NFTs in AD brains. 

PMID- 24900373
TI  - Ligand-Based Site of Metabolism Prediction for Cytochrome P450 2D6.
AB  - A ligand-based method based on the SMARTCyp approach that predicts the sites of
      cytochrome P450 2D6-mediated metabolism of druglike molecules has been developed.
      The method uses only two descriptors besides the reactivity from SMARTCyp: the
      distance to a protonated nitrogen atom and the distance to the end of the
      molecule. Hence, the site of metabolism is predicted directly from the 2D
      structure of a molecule, without requiring calculation of electronic properties
      or generation of 3D structures. Testing on an independent test set gives an area
      under the curve value of 0.94, and a site of metabolism is found among the top
      two ranked atoms for 91% of the compounds. 

PMID- 24900372
TI  - Discovery of SCH 900271, a Potent Nicotinic Acid Receptor Agonist for the
      Treatment of Dyslipidemia.
AB  - Structure-guided optimization of a series of C-5 alkyl substituents led to the
      discovery of a potent nicotinic acid receptor agonist SCH 900271 (33) with an
      EC50 of 2 nM in the hu-GPR109a assay. Compound 33 demonstrated good oral
      bioavailability in all species. Compound 33 exhibited dose-dependent inhibition
      of plasma free fatty acid (FFA) with 50% FFA reduction at 1.0 mg/kg in fasted
      male beagle dogs. Compound 33 had no overt signs of flushing at doses up to 10
      mg/kg with an improved therapeutic window to flushing as compared to nicotinic
      acid. Compound 33 was evaluated in human clinical trials. 

PMID- 24900375
TI  - Factor D Inhibitors for the Treatment of AMD: Patent Highlight.

PMID- 24900374
TI  - Optimization of a Potent, Orally Active S1P1 Agonist Containing a Quinolinone
      Core.
AB  - The optimization of a series of S1P1 agonists with limited activity against S1P3
      is reported. A polar headgroup was used to improve the physicochemical and
      pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3
      mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant
      lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose
      proportional increase in exposure was measured when 22 was dosed orally at 2 and
      100 mg/kg. 

PMID- 24900376
TI  - Combatting Drug-Resistant Bacteria with Gyrase and Topoisomerase IV Inhibitors:
      Patent Highlight.

PMID- 24900377
TI  - Novel use of leflunomide and malononitrilamides: patent highlight.

PMID- 24900378
TI  - Use of bupropion in the treatment of sexual dysfunction: patent highlight.

PMID- 24900379
TI  - Imidazotriazinone compounds: patent highlight.

PMID- 24900380
TI  - Novel compounds for the treatment of neurodegenerative diseases: patent
      highlight.

PMID- 24900381
TI  - Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7
      and USP47.
AB  - Inhibitors of the cancer-related cysteine isopeptidase human ubiquitin-specific
      proteases 7 (USP7) and 47 (USP47) are considered to have potential as cancer
      therapeutics, owing to their ability to stabilize the tumor suppressor p53 and to
      decrease DNA polymerase beta (Polbeta), both of which are potential anticancer
      effects. A new class of dual small molecule inhibitors of these enzymes has been
      discovered. Compound 1, a selective inhibitor of USP7 and USP47 with moderate
      potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and
      apoptosis in cancer cell lines. Compound 1 has been shown to demonstrate modest
      activity in human xenograft multiple myeloma and B-cell leukemia in vivo models.
      This activity may be the result of dual inhibition of USP7 and USP47. To address
      issues regarding potency and developability, analogues of compound 1 have been
      synthesized and tested, leading to improvements in potency, solubility, and
      metabolic reactivity profile. Further optimization is expected to yield
      preclinical candidates and, ultimately, clinical candidates for the treatment of
      multiple myeloma, prostate cancer, and other cancers. 

PMID- 24900382
TI  - Discovery of 2-Alkyl-1-arylsulfonylprolinamides as 11beta-Hydroxysteroid
      Dehydrogenase Type 1 Inhibitors.
AB  - On the basis of scaffold hopping, a novel series of 2-alkyl-1
      arylsulfonylprolinamides was discovered as 11beta-hydroxysteroid dehydrogenase
      type 1 (11beta-HSD-1) inhibitors. A representative compound 4ek, obtained through
      SAR and structure optimization studies, demonstrates excellent in vitro potency
      against 11beta-HSD-1 and dose-dependent in vivo inhibition of 11beta-HSD-1 in a
      prednisone/prednisolone transformation biomarker study in mice. 

PMID- 24900383
TI  - Synthesis of [(11)C]Am80 via Novel Pd(0)-Mediated Rapid [(11)C]Carbonylation
      Using Arylboronate and [(11)C]Carbon Monoxide.
AB  - (11)C-labeled methylbenzoates [(11)C]4a-d were synthesized using Pd(0)-mediated
      rapid cross-coupling reactions employing [(11)C]carbon monoxide and arylboronic
      acid neopentyl glycol esters 3a-d under atmospheric pressure in methanol
      dimethylformamide (MeOH-DMF), in radiochemical yields of 12 +/- 5-26 +/- 13%
      (decay-corrected based on [(11)C]O). The reaction conditions were highly
      favorable for the synthesis of [(11)C]Am80 ([(11)C]2) and [(11)C]methyl 4
      ((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl)benzoate
      ([(11)C]2-Me) using 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N-(5,5,8,8
      tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)benzamide (5), both of which
      produced a decay-corrected radiochemical yield (RCY) of 26 +/- 13%, with >99%
      radiochemical purity and an average specific radioactivity of 44 GBq/MUmol. The
      yields of [(11)C]4a, [(11)C]2-Me, and [(11)C]2 were improved by the use of a 2
      fold excess of the solvents and reagents under the same conditions to give
      respective yields of 66 +/- 8, 65 +/- 7, and 48 +/- 2%. 

PMID- 24900384
TI  - Antifungal spectrum, in vivo efficacy, and structure-activity relationship of
      ilicicolin h.
AB  - Ilicicolin H is a polyketide-nonribosomal peptide synthase (NRPS)-natural product
      isolated from Gliocadium roseum, which exhibits potent and broad spectrum
      antifungal activity, with sub-MUg/mL MICs against Candida spp., Aspergillus
      fumigatus, and Cryptococcus spp. It showed a novel mode of action, potent
      inhibition (IC50 = 2-3 ng/mL) of the mitochondrial cytochrome bc1 reductase, and
      over 1000-fold selectivity relative to rat liver cytochrome bc1 reductase.
      Ilicicolin H exhibited in vivo efficacy in murine models of Candida albicans and
      Cryptococcus neoformans infections, but efficacy may have been limited by high
      plasma protein binding. Systematic structural modification of ilicicolin H was
      undertaken to understand the structural requirement for the antifungal activity.
      The details of the biological activity of ilicicolin H and structural
      modification of some of the key parts of the molecule and resulting activity of
      the derivatives are discussed. These data suggest that the beta-keto group is
      critical for the antifungal activity. 

PMID- 24900386
TI  - Structure-activity relationships for side chain oxysterol agonists of the
      hedgehog signaling pathway.
AB  - Oxysterols (OHCs) are byproducts of cholesterol oxidation that are known to
      activate the Hedeghog (Hh) signaling pathway. While OHCs that incorporate
      hydroxyl groups throughout the scaffold are known, those that act as agonists of
      Hh signaling primarily contain a single hydroxyl on the alkyl side chain. We
      sought to further explore how side chain hydroxylation patterns affect oxysterol
      mediated Hh activation, by performing a structure-activity relationship study on
      a series of synthetic OHCs. The most active analogue, 23(R)-OHC (35),
      demonstrated potent activation of Hh signaling in two Hh-dependent cell lines
      (EC50 values 0.54-0.65 MUM). In addition, OHC 35 was approximately 3-fold
      selective for the Hh pathway as compared to the liver X receptor, a nuclear
      receptor that is also activated by endogenous OHCs. Finally, 35 induced
      osteogenic differentiation and osteoblast formation in cultured cells, indicating
      functional agonism of the Hh pathway. 

PMID- 24900385
TI  - Aryl Piperazinyl Ureas as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) in Rat,
      Dog, and Primate.
AB  - A series of aryl piperazinyl ureas that act as covalent inhibitors of fatty acid
      amide hydrolase (FAAH) is described. A potent and selective (does not inhibit
      FAAH-2) member of this class, JNJ-40355003, was found to elevate the plasma
      levels of three fatty acid amides: anandamide, oleoyl ethanolamide, and palmitoyl
      ethanolamide, in the rat, dog, and cynomolgous monkey. The elevation of the
      levels of these lipids in the plasma of monkeys suggests that FAAH-2 may not play
      a significant role in regulating plasma levels of fatty acid ethanolamides in
      primates. 

PMID- 24900387
TI  - Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based
      docking and molecular dynamics.
AB  - We have discovered a novel chemical class of inhibitors of the EphB4 tyrosine
      kinase by fragment-based high-throughput docking followed by explicit solvent
      molecular dynamics simulations for assessment of the binding mode. The synthesis
      of a single derivative (compound 7) of the hit identified in silico has resulted
      in an improvement of the inhibitory potency in an enzymatic assay from 8.4 MUM to
      160 nM and a ligand efficiency of 0.39 kcal/mol per non-hydrogen atom. Such
      remarkable improvement in affinity is due to an additional hydroxyl group
      involved in two favorable (buried) hydrogen bonds as predicted by molecular
      dynamics and validated by the crystal structure of the complex with EphA3 solved
      at 1.7 A resolution. 

PMID- 24900388
TI  - Identification of the Significant Involvement and Mechanistic Role of CYP3A4/5 in
      Clopidogrel Bioactivation.
AB  - The clinical response to the antiplatelet prodrug clopidogrel is associated with
      high intersubject variability and a certain level of therapeutic resistance.
      Previous studies have suggested that genetic polymorphism of CYP2C19 might be one
      determinant of clopidogrel efficacy and led to the CYP2C19 genotype-tailored
      antithrombotic therapy. However, evidence against the role of CYP2C19 from
      multiple studies implied the involvement of other factors. Here, we report that
      prodrug activation of the thiophene motif in clopidogrel is attenuated by heavy
      metabolic attrition of the piperidine motif. CYP3A4/5 was identified to be the
      enzyme metabolizing the piperidine motif. Inhibiting CYP3A4/5-mediated attrition
      was shown to potentiate active metabolite formation, which was found to be
      catalyzed by multiple CYP enzymes. Identifying the significant involvement of
      CYP3A4/5 and characterizing its mechanistic role in clopidogrel bioactivation
      might assist future pharmacogenomic studies in exploring the full mechanism
      underlying clopidogrel efficacy. 

PMID- 24900389
TI  - Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in
      Vivo.
AB  - Optimization of a series of R132H IDH1 inhibitors from a high throughput screen
      led to the first potent molecules that show robust tumor 2-HG inhibition in a
      xenograft model. Compound 35 shows good potency in the U87 R132H cell based assay
      and ~90% tumor 2-HG inhibition in the corresponding mouse xenograft model
      following BID dosing. The magnitude and duration of tumor 2-HG inhibition
      correlates with free plasma concentration. 

PMID- 24900391
TI  - Approaches toward new Alzheimer's treatments.

PMID- 24900392
TI  - "It Ain't Over 'til It's Over" (a) -The Search for Treatments and Cures for
      Alzheimer's Disease.
AB  - In the neuroscience landscape, there is no condition with higher unmet medical
      and societal need than Alzheimer's disease (AD). There are significant
      opportunities to improve upon symptomatic treatments in AD, and as yet, there are
      no treatments to modify (slow, stop, or prevent) underlying disease progression.
      Our goals are to discover new symptomatic AD therapies with improved efficacy and
      longevity; to complete definitive studies that refute or prove the amyloid
      hypothesis, potentially opening multiple avenues to new therapeutic modalities;
      and to initiate tests of novel mechanisms that can prevent tau pathology and
      neurodegeneration. It's a critical time in the testing of novel AD therapeutics
      let's hope we succeed. 

PMID- 24900390
TI  - Kinetic profile of amyloid formation in the presence of an aromatic inhibitor by
      nuclear magnetic resonance.
AB  - The self-assembly of amyloid proteins into beta-sheet rich assemblies is
      associated with human amyloidoses including Alzheimer's disease, Parkinson's
      disease, and type 2 diabetes. An attractive therapeutic strategy therefore is to
      develop small molecules that would inhibit protein self-assembly. Natural
      polyphenols are potential inhibitors of beta-sheet formation. How these compounds
      affect the kinetics of self-assembly studied by thioflavin T (ThT) fluorescence
      is not understood primarily because their presence interferes with ThT
      fluorescence. Here, we show that by plotting peak intensities from nuclear
      magnetic resonance (NMR) against incubation time, kinetic profiles in the
      presence of the polyphenol can be obtained from which kinetic parameters of self
      assembly can be easily determined. In applying this technique to the self
      assembly of the islet amyloid polypeptide in the presence of curcumin, a
      biphenolic compound found in turmeric, we show that the kinetic profile is
      atypical in that it shows a prenucleation period during which there is no
      observable decrease in NMR peak intensities. 

PMID- 24900393
TI  - BACE Inhibitors: Potential Treatment of Alzheimer's Disease, Dementia, and
      Related Neurodegenerative Disorders (A): 5,6-Dihydroimidazo[1,2-a]pyrazin-8-yl
      amine Derivatives: Patent Highlight.

PMID- 24900394
TI  - BACE Inhibitors: Potential Treatment of Alzheimer's Disease, Dementia, and
      Related Neurodegenerative Disorders (B): 3-Amino-4-fluoro-1H-isoindol
      Derivatives: Patent Highlight.

PMID- 24900395
TI  - BACE-Inhibitors: Potential Treatment of Alzheimer Disease, Dementia, and Related
      Neurodegenerative Diseases. C. Spiro-Heterocyclic Derivatives: Patent Highlight.

PMID- 24900396
TI  - 5-Amino-oxazepine and 5-Amino-thiazepine Compounds as beta-Secretase Antagonists
      and Methods of Use: Patent Highlight.

PMID- 24900397
TI  - Compounds and Their Use as BACE Inhibitors: Patent Highlight.

PMID- 24900398
TI  - Novel indolethylbenzamides for the treatment of tauopathies: patent highlight.

PMID- 24900399
TI  - Novel and selective inhibitors of histone deacetylase: patent highlight.

PMID- 24900400
TI  - Benzenesulfonyl and Benzenesulfonamide as Modulators of the 5-HT6 Receptor:
      Patent Highlight.

PMID- 24900401
TI  - Novel Benzoisoxazole as Partial Agonist of the 5-HT4 Receptor: Patent Highlight.

PMID- 24900402
TI  - Novel Quinolinones as Activators of AMP Activated Protein Kinase: Patent
      Highlight.

PMID- 24900403
TI  - A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of beta
      Secretase.
AB  - beta-Secretase inhibitors are potentially disease-modifying treatments for
      Alzheimer's disease. Previous efforts in our laboratory have resulted in
      hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against
      beta-site amyloid precursor protein cleaving enzyme (BACE). When dosed
      intravenously, compound 1 was also shown to significantly reduce Abeta40 levels
      in plasma, brain, and cerebral spinal fluid. Herein, we report further
      optimizations that led to the discovery of inhibitor 16 as a novel, potent, and
      orally efficacious BACE inhibitor. 

PMID- 24900404
TI  - Discovery of SCH 900229, a Potent Presenilin 1 Selective gamma-Secretase
      Inhibitor for the Treatment of Alzheimer's Disease.
AB  - An exploration of the SAR of the side chain of a novel tricyclic series of gamma
      secretase inhibitors led to the identification of compound (-)-16 (SCH 900229),
      which is a potent and PS1 selective inhibitor of gamma-secretase (Abeta40 IC50 =
      1.3 nM). Compound (-)-16 demonstrated excellent lowering of Abeta after oral
      administration in preclinical animal models and was advanced to human clinical
      trials for further development as a therapeutic agent for the treatment of
      Alzheimer's disease. 

PMID- 24900405
TI  - Identification of aminopyridazine-derived antineuroinflammatory agents effective
      in an Alzheimer's mouse model.
AB  - Targeting neuroinflammation may be a new strategy to combat Alzheimer's disease.
      An aminopyridazine 1b previously reported as a novel antineuroinflammatory agent
      was considered to have a potential therapeutic effect for Alzheimer's disease. In
      this study, we further explored the chemical space to identify more potent
      antineuroinflammatory agents and validate their in vivo efficacy in an animal
      model. Compound 14 was finally identified as an effective agent with comparable
      in vivo efficacy to the marketed drug donepezil in counteracting spatial learning
      and working memory impairment in an Abeta-induced Alzheimer's mouse model. 

PMID- 24900406
TI  - Initial Optimization of a New Series of gamma-Secretase Modulators Derived from a
      Triterpene Glycoside.
AB  - The discovery of a new series of gamma-secretase modulators is disclosed.
      Starting from a triterpene glycoside gamma-secretase modulator that gave a very
      low brain-to-plasma ratio, initial SAR and optimization involved replacement of a
      pendant sugar with a series of morpholines. This modification led to two
      compounds with significantly improved central nervous system (CNS) exposure. 

PMID- 24900407
TI  - Neuroprotective Tri- and Tetracyclic BChE Inhibitors Releasing Reversible
      Inhibitors upon Carbamate Transfer.
AB  - Tri- and tetracyclic nitrogen-bridgehead compounds were designed and synthesized
      to yield micromolar cholinesterase (ChE) inhibitors. Structure-activity
      relationships identified potent compounds with butyrylcholinesterase selectivity.
      These compounds were selected as starting points for the design and synthesis of
      carbamate-based (pseudo)irreversible inhibitors. Compounds with superior
      inhibitory activity and selectivity were obtained and kinetically characterized
      also with regard to the velocity of enzyme carbamoylation. Structural elements
      were identified and introduced that additionally showed neuroprotective
      properties on a hippocampal neuronal cell line (HT-22) after glutamate-induced
      intracellular reactive oxygen species generation. We have identified potent and
      selective pseudoirreversible butyrylcholinesterase inhibitors that release
      reversible inhibitors with neuroprotective properties after carbamate transfer to
      the active site of cholinesterases. 

PMID- 24900408
TI  - Nonpeptidic lysosomal modulators derived from z-phe-ala-diazomethylketone for
      treating protein accumulation diseases.
AB  - Lysosomes are involved in protein turnover and removing misfolded species, and
      their enzymes have the potential to offset the defect in proteolytic clearance
      that contributes to the age-related dementia Alzheimer's disease (AD). The weak
      cathepsin B and L inhibitor Z-Phe-Ala-diazomethylketone (PADK) enhances lysosomal
      cathepsin levels at low concentrations, thereby eliciting protective clearance of
      PHF-tau and Abeta42 in the hippocampus and other brain regions. Here, a class of
      positive modulators is established with compounds decoupled from the cathepsin
      inhibitory properties. We utilized PADK as a departure point to develop
      nonpeptidic structures with the hydroxyethyl isostere. The first-in-class
      modulators SD1002 and SD1003 exhibit improved levels of cathepsin up-regulation
      but almost complete removal of cathepsin inhibitory properties as compared to
      PADK. Isomers of the lead compound SD1002 were synthesized, and the modulatory
      activity was determined to be stereoselective. In addition, the lead compound was
      tested in transgenic mice with results indicating protection against AD-type
      protein accumulation pathology. 

PMID- 24900409
TI  - Synthesis and SAR Studies of Fused Oxadiazines as gamma-Secretase Modulators for
      Treatment of Alzheimer's Disease.
AB  - Fused oxadiazines (3) were discovered as selective and orally bioavailable gamma
      secretase modulators (GSMs) based on the structural framework of oxadiazoline
      GSMs. Although structurally related, initial modifications showed that structure
      activity relationships (SARs) did not translate from the oxadiazoline to the
      oxadiazine series. Subsequent SAR studies on modifications at the C3 and C4
      positions of the fused oxadiazine core helped to identify GSMs such as compounds
      8r and 8s that were highly efficacious in vitro and in vivo in a number of animal
      models with highly desirable physical and pharmacological properties. Further
      improvements of in vitro activity and selectivity were achieved by the
      preparation of fused morpholine oxadiazines. The shift in specificity of APP
      cleavage rather than a reduction in overall gamma-secretase activity and the lack
      of changes in substrate accumulation and Notch processing as observed in the
      animal studies of compound 8s confirm that the oxadiazine series of compounds are
      potent GSMs. 

PMID- 24900411
TI  - Minimizing Drug Exposure in the CNS while Maintaining Good Oral Absorption.
AB  - In some drug discovery approaches, it is advantageous to restrict the access of
      compounds to the CNS to minimize the risk of side effects. By choosing
      appropriate physicochemical properties and building in the ability to act as
      substrates for active efflux transporters, it is possible to achieve CNS
      restriction and still retain sufficient absorption through the intestinal
      epithelium to retain good oral bioavailability. Potential risks in employing this
      approach are considered. 

PMID- 24900410
TI  - Evaluation of [(11)C]N-Methyl Lansoprazole as a Radiopharmaceutical for PET
      Imaging of Tau Neurofibrillary Tangles.
AB  - [(11)C]N-Methyl lansoprazole ([(11)C]NML, 3) was synthesized and evaluated as a
      radiopharmaceutical for quantifying tau neurofibrillary tangle (NFT) burden using
      positron emission tomography (PET) imaging. [(11)C]NML was synthesized from
      commercially available lansoprazole in 4.6% radiochemical yield (noncorrected
      RCY, based upon [(11)C]MeI), 99% radiochemical purity, and 16095 Ci/mmol specific
      activity (n = 5). Log P was determined to be 2.18. A lack of brain uptake in
      rodent microPET imaging revealed [(11)C]NML to be a substrate for the rodent
      permeability-glycoprotein 1 (PGP) transporter, but this could be overcome by
      pretreating with cyclosporin A to block the PGP. Contrastingly, [(11)C]NML was
      not found to be a substrate for the primate PGP, and microPET imaging in rhesus
      revealed [(11)C]NML uptake in the healthy primate brain of ~1600 nCi/cc maximum
      at 3 min followed by rapid egress to 500 nCi/cc. Comparative autoradiography
      between wild-type rats and transgenic rats expressing human tau (hTau +/+)
      revealed 12% higher uptake of [(11)C]NML in the cortex of brains expressing human
      tau. Further autoradiography with tau positive brain samples from progressive
      supranuclear palsy (PSP) patients revealed colocalization of [(11)C]NML with tau
      NFTs identified using modified Bielschowsky staining. Finally, saturation binding
      experiments with heparin-induced tau confirmed K d and Bmax values of [(11)C]NML
      as 700 pM and 0.214 fmol/MUg, respectively. 

PMID- 24900412
TI  - Preparation of N-(Hetero)cyclyl Benzamides as Inhibitors of the Activity of
      Complex III of the Mitochondrial Electron Transport Chain: Patent Highlight.

PMID- 24900413
TI  - Preparation of Novel Pyrazolyl Guanidine as F1F0-ATPase Inhibitors: Patent
      Highlight.

PMID- 24900414
TI  - Pharmaceutical composition comprising indole compound for treatment of diseases
      associated with oxidative stress: patent highlight.

PMID- 24900415
TI  - Compositions and methods for the treatment of mitochondrial diseases: patent
      highlight.

PMID- 24900416
TI  - GPR119 Modulators for the Treatment of Diabetes, Obesity, and Related Diseases:
      Patent Highlight.

PMID- 24900417
TI  - Development of Synthetic Aminopeptidase N/CD13 Inhibitors to Overcome Cancer
      Metastasis and Angiogenesis.
AB  - Cancer metastasis is a major barrier to its treatment and an important cause of
      patient death. Antimetastatic agents hold promise for patients with advanced
      metastatic tumors. Aminopeptidase N/CD13 (APN) is being pursued by many as an
      important target against cancer metastasis and angiogenesis, but there are few
      reports on the in vivo evaluation of synthetic APN inhibitors. Herein, a series
      of compounds targeting APN were synthesized and evaluated for their
      antimetastasis and antiangiogenesis potency both in vitro and in vivo.
      Excitingly, compounds 4m, 4t, and 4cc, with the most potent APN inhibitory
      activities, displayed significant antimetastasis and antiangiogenesis effects in
      vitro and in vivo, suggesting that those synthetic APN inhibitors have the
      potential to overcome cancer metastasis and angiogenesis. 

PMID- 24900418
TI  - Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of
      MGMT and MMR.
AB  - The imidazotetrazine ring is an acid-stable precursor and prodrug of highly
      reactive alkyl diazonium ions. We have shown that this reactivity can be managed
      productively in an aqueous system for the generation of aziridinium ions with 96%
      efficiency. The new compounds are potent DNA alkylators and have antitumor
      activity independent of the O6-methylguanine-DNA methyltransferase and DNA
      mismatch repair constraints that limit the use of Temozolomide. 

PMID- 24900419
TI  - Peptides and Pseudopeptides as SIRT6 Deacetylation Inhibitors.
AB  - SIRT6 belongs to the family of histone deacetylases (class III), but it also has
      mono-ADP-ribosyltransferase activity. SIRT6 is a nuclear sirtuin that has been
      associated with aging, cellular protection, and sugar metabolism. Despite these
      important roles for SIRT6, thus far, there are only a few weak SIRT6 inhibitors
      available, and no structure-activity relationship (SAR) studies have been
      published. This is the first study concerning peptides and pseudopeptides as
      SIRT6 deacetylation inhibitors and the first SAR data concerning SIRT6. We also
      investigated the molecular interactions using a homology model. We report three
      compounds exhibiting 62-91% SIRT6 inhibition at 200 MUM concentration. These
      compounds can serve as starting points for systematic SAR studies and SIRT6
      inhibitor design. 

PMID- 24900420
TI  - Tuning the activity of a short arg-trp antimicrobial Peptide by lipidation of a C
      or N-terminal lysine side-chain.
AB  - The attachment of lipids to C- or N-terminally positioned lysine side-chain amino
      groups increases the activity of a short synthetic (Arg-Trp)3 antimicrobial
      peptide significantly, making these peptides even active against pathogenic Gram
      negative bacteria. Thus, a peptide with strong activity against S. aureus (1.1-2
      MUM) and good activity against A. baumannii and P. aeruginosa (9-18 MUM) was
      identified. The most promising peptide causes 50% hemolysis at 285 MUM and shows
      some selectivity against human cancer cell lines. Interestingly, the increased
      activity of ferrocenoylated peptides is mostly due to the lipophilicity of the
      organometallic fragment. 

PMID- 24900421
TI  - Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth
      Factor Receptor-Family Kinases.
AB  - A series of potent, selective platelet-derived growth factor receptor-family
      kinase inhibitors was optimized starting from a globally selective lead molecule
      4 through structural modifications aimed at improving the physiochemical and
      pharmacokinetic properties, as exemplified by 18b. Further clearance reduction
      via per-methylation of the alpha-carbons of a solubilizing piperidine nitrogen
      resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a
      collagen-induced arthritis model, and a 7 day rat in vivo tolerability study
      culminated in the selection of compound 22b (AC710) as a preclinical development
      candidate. 

PMID- 24900422
TI  - Gd Complexes of DO3A-(Biphenyl-2,2'-bisamides) Conjugates as MRI Blood-Pool
      Contrast Agents.
AB  - We report the synthesis of DO3A derivatives of 2,2'-diaminobiphenyl (1a,b) and
      their Gd complexes of the type [Gd(1)(H2O)].xH2O (2a,b) for use as new MRI blood
      pool contrast agents (BPCAs) that provide strong and prolonged vascular
      enhancement. Pharmacokinetic inertness of 2 compares well with that of
      structurally related Dotarem, a DOTA-based MRI CA currently in use. The R 1
      relaxivity in water reaches 7.3 mM(-1) s(-1), which is approximately twice as
      high as that of Dotarem (R 1 = 3.9 mM(-1) s(-1)). They show interaction with HSA
      to give association constants (K a) in the order of two (~10(2)), revealing the
      existence of the blood-pool effect. The in vivo MR images of mice obtained with 2
      are coherent, showing strong signal enhancement in both heart, abdominal aorta,
      and small vessels. Furthermore, the brain tumor is vividly enhanced for an
      extended period of time. 

PMID- 24900423
TI  - Strain-Promoted Catalyst-Free Click Chemistry for Rapid Construction of (64)Cu
      Labeled PET Imaging Probes.
AB  - A rapid, efficient, and catalyst-free click chemistry method for the construction
      of (64)Cu-labeled PET imaging probes was reported based on the strain-promoted
      aza-dibenzocyclooctyne ligation. This new method was exemplified in the synthesis
      of (64)Cu-labeled RGD peptide for PET imaging of tumor integrin alphavbeta3
      expression in vivo. The catalyst-free click chemistry reaction proceeded with a
      fast rate and eliminated the contamination problem of the catalyst Cu(I) ions
      interfering with the (64)Cu radiolabeling procedure under the conventional Cu
      catalyzed 1,3-dipolar cycloaddition condition. The new strategy is simple and
      robust, and the resultant (64)Cu-labeled RGD probe was obtained in an excellent
      yield and high specific activity. PET imaging and biodistribution studies
      revealed significant, specific uptake of the "click" (64)Cu-labeled RGD probe in
      integrin alphavbeta3-positive U87MG xenografts with little uptake in nontarget
      tissues. This new approach is versatile, which warrants a wide range of
      applications for highly diverse radiometalated bioconjugates for radioimaging and
      radiotherapy. 

PMID- 24900424
TI  - SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for
      Huntington's Disease.
AB  - We report a series of irreversible transglutaminase 2 inhibitors starting from a
      known lysine dipeptide bearing an acrylamide warhead. We established new SARs
      resulting in compounds demonstrating improved potency and better physical and
      calculated properties. Transglutaminase selectivity profiling and in vitro ADME
      properties of selected compounds are also reported. 

PMID- 24900425
TI  - Discovery of a 4-Azetidinyl-1-thiazoyl-cyclohexane CCR2 Antagonist as a
      Development Candidate.
AB  - We have discovered a novel series of 4-azetidinyl-1-aryl-cyclohexanes as CCR2
      antagonists. Divergent SAR studies on hCCR2 and hERG activities led to the
      discovery of compound 8d, which displayed good hCCR2 binding affinity (IC50, 37
      nM) and potent functional antagonism (chemotaxis IC50, 30 nM). It presented an
      IC50 of >50 MUM in inhibition of the hERG channel and had no effect on the QTc
      interval up to 10 mg/kg (i.v.) in anesthetized guinea pig and dog CV studies. It
      also displayed high selectivity over other chemokine receptors and GPCRs, and
      amendable oral bioavailability in dogs and primates. In a thioglycollate-induced
      inflammation model in hCCR2KI mice, it had ED50 of 3 mg/kg on inhibition of the
      influx of leukocytes, monocytes/macrophages, and T-lymphocytes. 

PMID- 24900426
TI  - A new approach to explore the binding space of polysaccharide-based ligands:
      selectin antagonists.
AB  - The discovery of molecules that interfere with the binding of a ligand to a
      receptor remains a topic of great interest in medicinal chemistry. Herein, we
      report that a monosaccharide unit of a polysaccharide ligand can be replaced
      advantageously by a conformationally locked acyclic molecular entity. A cyclic
      component of the selectin ligand Sialyl Lewis(x), GlcNAc, is replaced by an
      acyclic tether, tartaric esters, which link two saccharide units. The
      conformational bias of this acyclic tether originates from the minimization of
      intramolecular dipole-dipole interaction and the gauche effect. The evaluation of
      the binding of these derivatives to P-selectin was measured by surface plasmon
      resonance spectroscopy. The results obtained in our pilot study suggest that the
      discovery of tunable tethers could facilitate the exploration of the carbohydrate
      recognition domain of various receptors. 

PMID- 24900427
TI  - Inhibitors of the NAD(+)-Dependent Protein Desuccinylase and Demalonylase Sirt5.
AB  - NAD(+)-dependent histone deacetylases (sirtuins) play important roles in
      epigenetic regulation but also through nonhistone substrates for other key
      cellular events and have been linked to the pathogenesis of cancer,
      neurodegeneration, and metabolic diseases. The subtype Sirt5 has been shown
      recently to act as a desuccinylating and demalonylating enzyme. We have
      established an assay for biochemical testing of Sirt5 using a small labeled
      succinylated lysine derivative. We present a comparative study on the profiling
      of several established sirtuin inhibitors on Sirt1-3 as well as Sirt5 and also
      present initial results on a screening for new compounds that block Sirt5.
      Thiobarbiturates were identified as new Sirt5 inhibitors in the low micromolar
      range, which are selective over Sirt3 that can be found in the same cell
      compartment as Sirt5. 

PMID- 24900428
TI  - Structure-Based Design of Potent and Selective CK1gamma Inhibitors.
AB  - Aberrant activation of the Wnt pathway is believed to drive the development and
      growth of some cancers. The central role of CK1gamma in Wnt signal transduction
      makes it an attractive target for the treatment of Wnt-pathway dependent cancers.
      We describe a structure-based approach that led to the discovery of a series of
      pyridyl pyrrolopyridinones as potent and selective CK1gamma inhibitors. These
      compounds exhibited good enzyme and cell potency, as well as selectivity against
      other CK1 isoforms. A single oral dose of compound 13 resulted in significant
      inhibition of LRP6 phosphorylation in a mouse tumor PD model. 

PMID- 24900429
TI  - Synthesis and Anti-influenza A Virus Activity of 2,2-Dialkylamantadines and
      Related Compounds.
AB  - The synthesis of several 2,2-dialkyladamantyl-1-amines through the combination of
      a Ritter reaction with a Wagner-Meerwein rearrangement from noradamantane
      alcohols is reported. Several of the novel amines displayed low micromolar
      activities against several H1N1 influenza virus strains, including the amantadine
      resistant A/PuertoRico/8/34 strain. Most of the compounds did not show
      cytotoxicity for MDCK cells. 

PMID- 24900430
TI  - Identification of amides as carboxylic Acid surrogates for quinolizidinone-based
      m1 positive allosteric modulators.
AB  - Selective activation of the M1 muscarinic receptor via positive allosteric
      modulation represents an approach to treat the cognitive decline in patients with
      Alzheimer's disease. A series of amides were examined as a replacement for the
      carboxylic acid moiety in a class of quinolizidinone carboxylic acid M1
      muscarinic receptor positive allosteric modulators, and leading pyran 4o and
      cyclohexane 5c were found to possess good potency and in vivo efficacy. 

PMID- 24900431
TI  - Synthesis and antiproliferative activities of ottelione a analogues.
AB  - Through the syntheses of its C-1 desvinyl, C-7 methylene, C-7 exocyclic
      ethylidene, and various C-3 phenylmethyl analogues, the structure-activity
      relationship of antimitotic ottelione A (4) against tubulin and various cancer
      cells was established. The results indicated that compound 4 was a colchicine
      competitive inhibitor and that the C-1 vinyl group is unnecessary for its
      potency, whereas the C-7 exocyclic double bond is essential, possibly because of
      its irreversible interaction with tubulin. Further optimization of the
      substituents on the phenylmethyl group at the C-3 position generated compound 10g
      with a 3'-fluoro-4'-methoxyphenylmethyl substituent, which was 6-38-fold more
      active against MCF-7, NCI-H460, and COLO205 cancer cells relative to 4. Results
      from in vitro tubulin polymerization assay confirmed the potency of compounds 4,
      10g, and 11a. 

PMID- 24900434
TI  - Potentiating Metronidazole Scaffold against Resistant Trichomonas: Design,
      Synthesis, Biology and 3D-QSAR Analysis.
AB  - Metronidazole (MTZ), the FDA-approved drug against Trichomonas vaginalis (TV), is
      being challenged seriously by drug resistance, while its inertness to sperm makes
      it ineffective as a vaginal contraceptive. Thirteen piperidine dithiocarbamate
      hybrids of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethane (8-20) were designed to
      potentiate the MTZ framework against drug resistance and sperm. New compounds
      were 1.2-12.1 times more effective against MTZ-susceptible and -resistant strains
      of TV. All of the compounds exhibited high safety toward cervical (HeLa) cells
      and Lactobacillus. Thirty-eight compounds were scrutinized by CoMFA and CoMSIA
      techniques of 3D quantitative structure-activity relationship. Good predictive r
      pred (2) values for CoMFA and CoMSIA models reflected the robustness of the
      predictive ability. This was validated by designing five new analogues (46-50),
      which were potently microbicidal (3-10 and 10-20 times against MTZ-susceptible
      and -resistant TV, respectively) and spermicidal. This in vitro study may have
      significant clinical relevance, which could become evident in due course. 

PMID- 24900432
TI  - Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine
      Methyltransferase EZH2.
AB  - The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in
      regulating gene expression, and its aberrant activity is linked to the onset and
      progression of cancer. As part of a drug discovery program targeting EZH2, we
      have identified highly potent, selective, SAM-competitive, and cell-active EZH2
      inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small
      molecule chemical tools that would be useful to further explore the biology of
      EZH2. 

PMID- 24900435
TI  - Discovery of a Potent Dihydrooxadiazole Series of Non-ATP-Competitive MK2
      (MAPKAPK2) Inhibitors.
AB  - Inhibition of MK2 has been shown to offer advantages over that of p38 MAPK in the
      development of cures for inflammatory diseases such as arthritis. P38 MAPK
      knockout in mice was lethal, whereas MK2-null mice demonstrated strong inhibition
      of disease progression in collagen-induced arthritis and appeared normal and
      viable. However, it is challenging to develop ATP-competitive MK2 inhibitors due
      to high ATP binding affinity to the kinase. Non-ATP-competitive MK2 inhibitors
      interact and bind to the kinase in a mode independent of ATP concentration, which
      could provide better selectivity and cellular potency. Therefore, it is desirable
      to identify non-ATP-competitive MK2 inhibitors. Through structure optimization of
      lead compound 1, a novel series of dihydrooxadiazoles was discovered. Additional
      structure-activity relationship (SAR) study of this series led to the
      identification of compound 38 as a non-ATP-competitive MK2 inhibitor with potent
      enzymatic activity and good cellular potency. The SAR, synthesis, and biological
      data of dihydrooxadiazole series are discussed. 

PMID- 24900436
TI  - Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of
      Smoothened.
AB  - Inhibitors of the Hedgehog signaling pathway have generated a great deal of
      interest in the oncology area due to the mounting evidence of their potential to
      provide promising therapeutic options for patients. Herein, we describe the
      discovery strategy to overcome the issues inherent in lead structure 1 that
      resulted in the identification of Smoothened inhibitor 1-((2R,4R)-2-(1H
      benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (PF
      04449913, 26), which has been advanced to human clinical studies. 

PMID- 24900438
TI  - Future horizons in drug discovery research.

PMID- 24900437
TI  - Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases
      Inhibitor.
AB  - Structure-activity relationship analysis in a series of 3-(5-((2-oxoindolin-3
      ylidene)methyl)furan-2-yl)amides identified compound 13, a pan-Pim kinases
      inhibitor with excellent biochemical potency and kinase selectivity. Compound 13
      exhibited in vitro synergy with chemotherapeutics and robust in vivo efficacy in
      two Pim kinases driven tumor models. 

PMID- 24900439
TI  - Synthesis and biological evaluation of cyclic sulfamide derivatives as 11beta
      hydroxysteroid dehydrogenase 1 inhibitors.
AB  - A new series of cyclic sulfamide derivatives were synthesized and evaluated for
      their ability to inhibit 11beta-HSD1. Among this series, 18e showed good in vitro
      activity toward human 11beta-HSD1, selectivity against 11beta-HSD2, microsomal
      stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute
      toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey
      models. 

PMID- 24900440
TI  - Application of MM-GB/SA and WaterMap to SRC Kinase Inhibitor Potency Prediction.
AB  - WaterMap and MM-GB/SA scoring methods were applied to an extensive congeneric
      series of small-molecule SRC inhibitors with high-quality enzyme data and well
      characterized binding modes to compare the performance of these scoring methods
      in this data set and to provide insight into the relative strengths of each
      method. Only minor conformational changes in SRC bound with representative DFG-in
      class of inhibitors were demonstrated in previous studies; thus, the protein
      flexibility that normally presents a challenge to pose and potency predictions
      was minimized in this model system. While WaterMap correctly recognized major
      trends in the SAR of this series, MM-GB/SA performed better in ranking the
      relative ligand affinities. The different scoring methods were further analyzed
      to determine which aspects of series SAR were more amenable to MM-GB/SA than
      WaterMap scoring. 

PMID- 24900441
TI  - Negamycin analogue with readthrough-promoting activity as a potential drug
      candidate for duchenne muscular dystrophy.
AB  - A series of (+)-negamycin 1 analogues were synthesized, and their readthrough
      promoting activity was evaluated for nonsense mutations in Duchenne muscular
      dystrophy (DMD). A structure-activity relationship study indicated that 11b was
      the most potent drug candidate. Immunohistochemical analyses suggested that
      treatment with 11b restored dystrophin expression in mdx mice, a DMD mouse model.
      Furthermore, 11b decreased serum creatine kinase (CK) levels, an indicator of
      muscle fiber destruction. Most importantly, 11b demonstrated lower toxicity than
      1, and thus, it could be a useful candidate for long-term treatment of DMD. 

PMID- 24900442
TI  - Discovery of a Novel Series of CHK1 Kinase Inhibitors with a Distinctive Hinge
      Binding Mode.
AB  - A novel series of CHK1 inhibitors with a distinctive hinge binding mode,
      exemplified by 2-aryl-N-(2-(piperazin-1-yl)phenyl)thiazole-4-carboxamide, was
      discovered through high-throughput screening using the affinity selection-mass
      spectrometry (AS-MS)-based Automated Ligand Identification System (ALIS)
      platform. Structure-based ligand design and optimization led to significant
      improvements in potency to the single digit nanomolar range and hundred-fold
      selectivity against CDK2. 

PMID- 24900443
TI  - Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer
      Tumor Models.
AB  - Neurotrophins and their receptors (TRKs) play key roles in the development of the
      nervous system and the maintenance of the neural network. Accumulating evidence
      points to their role in malignant transformations, chemotaxis, metastasis, and
      survival signaling and may contribute to the pathogenesis of a variety of tumors
      of both neural and non-neural origin. By screening the GNF kinase collection, a
      series of novel oxindole inhibitors of TRKs were identified. Optimization led to
      the identification of GNF-5837 (22), a potent, selective, and orally bioavailable
      pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived
      from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good
      tool for the elucidation of TRK biology in cancer and other nononcology
      indications. 

PMID- 24900444
TI  - Heteroaromatic Moieties in the Sphingosine Backbone of alpha-Galactosylceramides
      for Noncovalent Interactions with CD1d.
AB  - A series of alpha-GalCer analogues containing heterocyclic and aromatic moieties
      in the sphingosine backbone were synthesized to improve the selectivity in the
      Th1/Th2 cytokine profile via noncovalent interaction with three aromatic residues
      at the binding pocket of CD1d. In vitro and in vivo biological evaluations
      revealed the treatment of alpha-GalCer analogue (6) induced the selective
      stimulation of natural killer T cells to facilitate the secretion of Th2
      cytokines. 

PMID- 24900445
TI  - Dual-target virtual screening by pharmacophore elucidation and molecular shape
      filtering.
AB  - Dual-target inhibitors gained increased attention in the past years. A novel in
      silico approach was employed for the discovery of dual 5-lipoxygenase/soluble
      epoxide hydrolase inhibitors. The ligand-based approach uses excessive
      pharmacophore elucidation and pharmacophore alignment in conjunction with shape
      based scoring. The virtual screening results were verified in vitro, leading to
      nine novel inhibitors including a dual-target compound. 

PMID- 24900447
TI  - Discovery of Natural Phenols as G Protein-Coupled Receptor-35 (GPR35) Agonists.
AB  - We report the discovery and characterization of natural phenols as G protein
      coupled receptor-35 (GPR35) agonists. Pharmacological characterization using
      label-free dynamic mass redistribution and Tango beta-arrestin translocation
      assays revealed that GPR35-active natural phenols are divergent in their biased
      agonism. 

PMID- 24900446
TI  - Virtual Screening and X-ray Crystallography for Human Kallikrein 6 Inhibitors
      with an Amidinothiophene P1 Group.
AB  - A series of compounds with an amidinothiophene P1 group and a pyrrolidinone
      sulphonamide scaffold linker was identified as potent inhibitors of human
      kallikrein 6 by structure-based virtual screening based on the union accessible
      binding space of serine proteases. As the first series of potent nonmechanism
      based hK6 inhibitors, they may be used as tool compounds for target validation.
      An X-ray structure of a representative compound complexed with hK6, resolved at a
      resolution of 1.88 A, revealed that the amidinothiophene moiety bound in the S1
      pocket and the pyrrolidinone-sulphonamide linker projected the aromatic tail into
      the S' pocket. 

PMID- 24900449
TI  - BACE1 Inhibitor Peptides: Can an Infinitely Small k cat Value Turn the Substrate
      of an Enzyme into Its Inhibitor?
AB  - Recently, we reported substrate-based pentapeptidic beta-secretase (BACE1)
      inhibitors with a hydroxymethylcarbonyl isostere as a substrate transition-state
      mimic. These inhibitors showed potent BACE1 inhibitory activity in enzyme and
      cell assays, with KMI-429 showing in vivo inhibition of Abeta production. We also
      designed and synthesized nonpeptidic and small-sized BACE1 inhibitors using "in
      silico conformational structure-based design". By studying the structure-activity
      relationship of these inhibitors, we found that the sigma-pi interaction of an
      inhibitor with the BACE1-Arg235 side chain played a key role in the inhibition of
      BACE1. We speculated that a peptide capable of binding to the BACE1-Arg235 side
      chain via the sigma-pi interaction might exhibit BACE1 inhibitory activity.
      Hence, we designed and synthesized a series of peptides that were modified at the
      P2 position and found that some of these peptides exhibited a potent BACE1
      inhibitory activity despite their structural similarity to the BACE1 substrate. 

PMID- 24900451
TI  - Drug discovery 2012 and beyond.

PMID- 24900452
TI  - The america invents act-overview and implications: patent highlight.

PMID- 24900450
TI  - Discovery of a potent thiadiazole class of histamine h3 receptor antagonist for
      the treatment of diabetes.
AB  - A series of novel 2-piperidinopiperidine thiadiazoles were synthesized and
      evaluated as new leads of histamine H3 receptor antagonists. The 4-(5-([1,4'
      bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)morpholine (5u)
      displayed excellent potency and ex vivo receptor occupancy. Compound 5u was also
      evaluated in vivo for antidiabetic efficacy in STZ diet-induced obesity type 2
      diabetic mice for 2 or 12 days. Non-fasting glucose levels were significantly
      reduced as compared with vehicle-treated mice. In addition, 5u dose dependently
      blocked the increase of HbA1c after 12 days of treatment. 

PMID- 24900453
TI  - A-ring dihalogenation increases the cellular activity of combretastatin-templated
      tetrazoles.
AB  - The combretastatins have been investigated for their antimitotic and antivascular
      properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is
      essential to maintain potent activity. We have synthesized new tetrazole
      analogues (32-34), demonstrating that 3,5-dihalogenation can consistently
      increase potency by up to 5-fold when compared to the equivalent trimethoxy
      compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer
      cells. Moreover, this increased potency offsets that lost by installing the
      tetrazole bridge into combretastatin A-4 (1), giving crystalline, soluble
      compounds that have low nanomolar activity, arrest cells in G2/M phase, and
      retain microtubule inhibitory activity. Molecular modeling has shown that
      optimized packing within the binding site resulting in increased Coulombic
      interaction may be responsible for this improved activity. 

PMID- 24900454
TI  - The First Dual ChE/FAAH Inhibitors: New Perspectives for Alzheimer's Disease?
AB  - The treatment of Alzheimer's disease (AD) still remains an area of significant
      unmet need, with drugs that only target the symptoms of the disease. Therefore,
      there is considerable need for disease-modifying therapies. The complex etiology
      of AD prompts scientists to develop multitarget strategies to combat causes and
      symptoms. To this aim, we designed, synthesized, and tested four new carbamates
      as dual cholinesterase-FAAH inhibitors. The dual activity of these compounds
      could lead to a potentially more effective treatment for the counteraction of AD
      progression, because they would allow regulation of both ACh and eCB signaling
      and improve neuronal transmission and/or counteract neuroinflammation. 

PMID- 24900455
TI  - Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II
      Inhibitors for Schizophrenia.
AB  - Kynurenine aminotransferase (KAT) II has been identified as a potential new
      target for the treatment of cognitive impairment associated with schizophrenia
      and other psychiatric disorders. Following a high-throughput screen, cyclic
      hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of
      human and rat KAT II. An X-ray crystal structure and (13)C NMR studies of PF
      04859989 bound to KAT II have demonstrated that this compound forms a covalent
      adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site.
      In vivo pharmacokinetic and efficacy studies in rat show that PF-04859989 is a
      brain-penetrant, irreversible inhibitor and is capable of reducing brain
      kynurenic acid by 50% at a dose of 10 mg/kg (sc). Preliminary structure-activity
      relationship investigations have been completed and have identified the positions
      on this scaffold best suited to modification for further optimization of this
      novel series of KAT II inhibitors. 

PMID- 24900457
TI  - Mitigating hERG Inhibition: Design of Orally Bioavailable CCR5 Antagonists as
      Potent Inhibitors of R5 HIV-1 Replication.
AB  - A series of CCR5 antagonists representing the thiophene-3-yl-methyl ureas were
      designed that met the pharmacological criteria for HIV-1 inhibition and mitigated
      a human ether-a-go-go related gene (hERG) inhibition liability. Reducing
      lipophilicity was the main design criteria used to identify compounds that did
      not inhibit the hERG channel, but subtle structural modifications were also
      important. Interestingly, within this series, compounds with low hERG inhibition
      prolonged the action potential duration (APD) in dog Purkinje fibers, suggesting
      a mixed effect on cardiac ion channels. 

PMID- 24900456
TI  - Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an
      Ophthalmic Solution for Treating Dry Eye.
AB  - LFA-1/ICAM-1 interaction is essential in support of inflammatory and specific T
      cell regulated immune responses by mediating cell adhesion, leukocyte
      extravasation, migration, antigen presentation, formation of immunological
      synapse, and augmentation of T-cell receptor signaling. The increase of ICAM-1
      expression levels in conjunctival epithelial cells and acinar cells was observed
      in animal models and patients diagnosed with dry eye. Therefore, it has been
      hypothesized that small molecule LFA-1/ICAM-1 antagonists could be an effective
      topical treatment for dry eye. In this letter, we describe the discovery of a
      potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonist (SAR 1118)
      and its development as an ophthalmic solution for treating dry eye. 

PMID- 24900459
TI  - NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with MU
      Opioid Agonist Activity.
AB  - A novel series of benzimidazole designed multiple ligands (DMLs) with activity at
      the neuronal nitric oxide synthase (nNOS) enzyme and the MU-opioid receptor was
      developed. Targeting of the structurally dissimilar heme-containing enzyme and
      the MU-opioid GPCR was predicated on the modulatory role of nitric oxide on MU
      opioid receptor function. Structure-activity relationship studies yielded lead
      compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 MUM),
      selectivity over both endothelial nitric oxide synthase (10-fold) and inducible
      nitric oxide synthase (125-fold), and potent MU-opioid binding affinity, K i =
      5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate
      secondary messenger assay resulted in full agonist activity (EC50 = 0.34 MUM).
      This work represents a novel approach in the development of new analgesics for
      the treatment of pain. 

PMID- 24900458
TI  - Discovery of a Novel Class of Bicyclo[3.1.0]hexanylpiperazines as Noncompetitive
      Neuropeptide Y Y1 Antagonists.
AB  - A novel class of bicyclo[3.1.0]hexanylpiperazine neuropeptide Y (NPY) Y1
      antagonists has been designed and synthesized. Scatchard binding analysis showed
      these compounds to be noncompetitive with [(125)I]PYY binding to the Y1 receptor.
      The most potent member, 1-((1alpha,3alpha,5alpha,6beta)-6-(3-ethoxyphenyl)-3
      methylbicyclo[3.1.0]hexan-6-yl)-4-phenylpiperazine (2) had an IC50 = 62 nM and
      displayed excellent oral bioavailability in rat (% F po = 80), as well as good
      brain penetration (B/P ratio = 0.61). In a spontaneous nocturnal feeding study
      with male Sprague-Dawley rats, 2 significantly reduced food intake during a 12 h
      period. 

PMID- 24900460
TI  - Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus
      NorA.
AB  - Thirty-two diverse compounds were evaluated for their ability to inhibit both Pgp
      mediated efflux in mouse T-lymphoma L5178 MDR1 and NorA-mediated efflux in S.
      aureus SA-1199B. Only four compounds were strong inhibitors of both efflux pumps.
      Three compounds were found to inhibit Pgp exclusively and strongly, while seven
      compounds inhibited only NorA. These results demonstrate that Pgp and NorA
      inhibitors do not necessarily overlap, opening the way to safer therapeutic use
      of effective NorA inhibitors. 

PMID- 24900461
TI  - Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for
      the Treatment of Obesity.
AB  - Extensive structure-activity relationship studies of a series derived from
      atropisomer 1, a previously described chiral benzodiazepine sulfonamide series,
      led to a potent, brain penetrant and selective compound with excellent
      preclinical pharmacokinetic across species. We also describe the utilization of a
      high throughput mouse pharmacodynamic assay which allowed for expedient
      assessment of pharmacokinetic and brain distribution. 

PMID- 24900463
TI  - Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5
      Modulators.
AB  - Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile
      acids from diverse animal species has led to the identification of avicholic acid
      as a selective but weak TGR5 agonist. Chemical modifications of this compound
      resulted in the disclosure of 6alpha-ethyl-16-epi-avicholic acid that shows
      enhanced potency at TGR5 and FXR receptors. The synthesis, biological appraisals,
      and structure-activity relationships of this series of compounds are herein
      described. Moreover, a thorough physicochemical characterization of 6alpha-ethyl
      16-epi-avicholic acid as compared to naturally occurring bile acids is reported
      and discussed. 

PMID- 24900465
TI  - Type 1 Phototherapeutic Agents. 2. Cancer Cell Viability and ESR Studies of
      Tricyclic Diarylamines.
AB  - Type 1 phototherapeutic agents based on diarylamines were assessed for free
      radical generation and evaluated in vitro for cell death efficacy in the U937
      leukemia cancer cell line. All of the compounds were found to produce copious
      free radicals upon photoexcitation with UV-A and/or UV-B light, as determined by
      electron spin resonance (ESR) spectroscopy. Among the diarylamines, the most
      potent compounds were acridan (4) and 9-phenylacridan (5), with IC50 values of
      0.68 MUM and 0.17 MUM, respectively. 

PMID- 24900464
TI  - Potent and Selective Inhibitors of CK2 Kinase Identified through Structure-Guided
      Hybridization.
AB  - In this paper we describe a series of 3-cyano-5-aryl-7-aminopyrazolo[1,5
      a]pyrimidine hits identified by kinase-focused subset screening as starting
      points for the structure-based design of conformationally constrained 6-acetamido
      indole inhibitors of CK2. The synthesis, SAR, and effects of this novel series on
      Akt signaling and cell proliferation in vitro are described. 

PMID- 24900466
TI  - Stimulation of Glucose-Dependent Insulin Secretion by a Potent, Selective sst3
      Antagonist.
AB  - This letter provides the first pharmacological proof of principle that the sst3
      receptor mediates glucose-stimulated insulin secretion (GSIS) from pancreatic
      beta-cells. To enable these studies, we identified the selective sst3 antagonist
      (1R,3R)-3-(5-phenyl-1H-imidazol-2-yl)-1-(tetrahydro-2H-pyran-4-yl)-2,3,4,9
      tetrahydro-1H-beta-carboline (5a), with improved ion channel selectivity and
      mouse pharmacokinetic properties as compared to previously described tetrahydro
      beta-carboline imidazole sst3 antagonists. We demonstrated that compound 5a
      enhances GSIS in pancreatic beta-cells and blocks glucose excursion induced by
      dextrose challenge in ipGTT and OGTT models in mice. Finally, we provided strong
      evidence that these effects are mechanism-based in an ipGTT study, showing
      reduction of glucose excursion in wild-type but not sst3 knockout mice. Thus, we
      have shown that antagonism of sst3 represents a new mechanism with potential in
      treating type 2 diabetes mellitus. 

PMID- 24900467
TI  - Heteronuclear Gd-(99m)Tc Complex of DTPA-Bis(histidylamide) Conjugate as a
      Bimodal MR/SPECT Imaging Probe.
AB  - The work describes the synthesis and in vivo application of heterotrimetallic
      complexes of the type {Gd(H2O)[(M(H2O)(CO)3)2(1)]} {1 = DTPA-bis(histidyl-amide);
      M = Re (3a); (99m)Tc (3b)} for dual modality MR/SPECT imaging. Here, the DTPA
      bis(histidylamide) conjugate functions as a trinucleating chelate incorporating
      Gd in the DTPA core with Re or (99m)Tc in the pair of histidylamide side arms.
      The two complexes are chemically equivalent as revealed by HPLC, and their
      "cocktail mixture" (3a + 3b) has demonstrated itself to be essentially a single
      bimodal imaging probe. The present system has thus overcome the sensitivity
      difference problem between MRI and SPECT and paved the way for practical
      applications. 

PMID- 24900468
TI  - An Orally Available 3-Ethoxybenzisoxazole Capsid Binder with Clinical Activity
      against Human Rhinovirus.
AB  - Respiratory infections caused by human rhinovirus are responsible for severe
      exacerbations of underlying clinical conditions such as asthma in addition to
      their economic cost in terms of lost working days due to illness. While several
      antiviral compounds for treating rhinoviral infections have been discovered, none
      have succeeded, to date, in reaching approval for clinical use. We have developed
      a potent, orally available rhinovirus inhibitor 6 that has progressed through
      early clinical trials. The compound shows favorable pharmacokinetic and activity
      profiles and has a confirmed mechanism of action through crystallographic studies
      of a rhinovirus-compound complex. The compound has now progressed to phase IIb
      clinical studies of its effect on natural rhinovirus infection in humans. 

PMID- 24900469
TI  - Analysis of Flexibility and Hotspots in Bcl-xL and Mcl-1 Proteins for the Design
      of Selective Small-Molecule Inhibitors.
AB  - Although Bcl-xL and Mcl-1, two antideath Bcl-2 members, have similar, flexible
      binding sites, they can achieve high binding selectivity to endogenous binding
      partners and synthetic small-molecule inhibitors. Here, we employed molecular
      dynamic (MD) simulations and hotspot analysis to investigate the conformational
      flexibility of these proteins and their binding hotspots at the binding sites.
      Backbone flexibility analyses indicate that the highest degree of flexibility in
      Mcl-1 is the alpha4 helical segment as opposed to the alpha3 helix in Bcl-xL
      among four helical segments in their binding sites. Furthermore, common and
      unique binding hotspots at both proteins were identified using small-molecule
      probes. These analyses can aid the design of potent and specific small-molecule
      inhibitors for these proteins. 

PMID- 24900470
TI  - Triazole Appending Agent (TAAG): A New Synthon for Preparing Iodine-Based
      Molecular Imaging and Radiotherapy Agents.
AB  - A new prosthetic group referred to as the triazole appending agent (TAAG) was
      developed as a means to prepare targeted radioiodine-based molecular imaging and
      therapy agents. Tributyltin-TAAG and the fluorous analogue were synthesized in
      high yield using simple click chemistry and the products labeled in greater than
      95% RCY with (123)I. A TAAG derivative of an inhibitor of prostate-specific
      membrane antigen was prepared and radiolabeled with (123)I in 85% yield where
      biodistribution studies in LNCap prostate cancer tumor models showed rapid
      clearance of the agent from nontarget tissues and tumor accumulation of 20%
      injected dose g(-1) at 1 h. The results presented demonstrate that the TAAG group
      promotes minimal nonspecific binding and that labeled conjugates can achieve high
      tumor uptake and exquisite target-to-nontarget ratios. 

PMID- 24900471
TI  - Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea
      Derivatives as Inhibitors of Complement.
AB  - A series of 1-phenyl-3-(1-phenylethyl)urea derivatives were identified as novel
      and potent complement inhibitors through structural modification of the original
      compound from high-throughput screening. Various analogues (7 and 13-15) were
      synthesized and identified as complement inhibitors, with the introduction of a
      five- or six-carbon chain (7c, 7d, 7k, 7l, and 7o) greatly improving their
      activity. Optimized compound 7l has an excellent inhibition activity with IC50
      values as low as 13 nM. We demonstrated that the compound 7l inhibited C9
      deposition through the classical, the lectin, and the alternative pathways but
      had no influence on C3 and C4 depositions. 

PMID- 24900472
TI  - Missing fragments: detecting cooperative binding in fragment-based drug design.
AB  - The aim of fragment-based drug design (FBDD) is to identify molecular fragments
      that bind to alternate subsites within a given binding pocket leading to
      cooperative binding when linked. In this study, the binding of fragments to human
      phenylethanolamine N-methyltransferase is used to illustrate how (a) current
      protocols may fail to detect fragments that bind cooperatively, (b) theoretical
      approaches can be used to validate potential hits, and (c) apparent false
      positives obtained when screening against cocktails of fragments may in fact
      indicate promising leads. 

PMID- 24900473
TI  - Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor.
AB  - A new class of HCV NS3/4a protease inhibitors containing a P2 to P4 macrocyclic
      constraint was designed using a molecular modeling-derived strategy. Building on
      the profile of previous clinical compounds and exploring the P2 and linker
      regions of the series allowed for optimization of broad genotype and mutant
      enzyme potency, cellular activity, and rat liver exposure following oral dosing.
      These studies led to the identification of clinical candidate 15 (MK-5172), which
      is active against genotype 1-3 NS3/4a and clinically relevant mutant enzymes and
      has good plasma exposure and excellent liver exposure in multiple species. 

PMID- 24900474
TI  - Discovery of BMS-846372, a Potent and Orally Active Human CGRP Receptor
      Antagonist for the Treatment of Migraine.
AB  - Calcitonin gene-related peptide (CGRP) receptor antagonists have been clinically
      shown to be effective in the treatment of migraine, but identification of potent
      and orally bioavailable compounds has been challenging. Herein, we describe the
      conceptualization, synthesis, and preclinical characterization of a potent,
      orally active CGRP receptor antagonist 5 (BMS-846372). Compound 5 has good oral
      bioavailability in rat, dog, and cynomolgus monkeys and overall attractive
      preclinical properties including strong (>50% inhibition) exposure-dependent in
      vivo efficacy in a marmoset migraine model. 

PMID- 24900475
TI  - A Back-to-Front Fragment-Based Drug Design Search Strategy Targeting the DFG-Out
      Pocket of Protein Tyrosine Kinases.
AB  - We present a straightforward process for the discovery of novel back pocket
      binding fragment molecules against protein tyrosine kinases. The approach begins
      by screening against the nonphosphorylated target kinase with subsequent
      counterscreening of hits against the phosphorylated enzyme. Back pocket-binding
      fragments are inactive against the phosphorylated kinase. Fragment molecules are
      of insufficient size to span both regions of the ATP binding pocket; thus, the
      outcome is binary (back pocket-binding or hinge-binding). Next, fragments with
      the appropriate binding profile are assayed in combination with a known hinge
      binding fragment and subsequently with a known back pocket-binding fragment.
      Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses
      candidate fragments to crystallization trials. The method is exemplified by a
      fragment screening campaign against vascular endothelial growth factor receptor
      2, and a novel back pocket-binding fragment is presented. 

PMID- 24900477
TI  - Inventorship and ownership considerations and pitfalls with collaborative
      research: patent highlight.
AB  - Collaborations can be very productive and beneficial for research. However, there
      are a number of considerations and pitfalls with regard to issues of inventorship
      and ownership that should be considered before entering into any research
      agreement to avoid the possible loss of patent rights. 

PMID- 24900478
TI  - The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase
      Activity.
AB  - Six focused rhodanine-based libraries, 60 compounds in total, were synthesized
      and evaluated as potential dynamin I GTPase inhibitors. Twenty-six were more
      potent than the lead compound with 13 returning IC50 values <=10 MUM, making the
      Rhodadyn series among the most active dynamin inhibitors reported. Two analogues
      were highly effective at blocking receptor-mediated endocytosis: C10 and D10 with
      IC50(RME) = 7.0 +/- 2.2 and 5.9 +/- 1.0 MUM, respectively. These compounds are
      equipotent with the best reported in-cell dynamin inhibitors. 

PMID- 24900479
TI  - Water-soluble progesterone analogues are effective, injectable treatments in
      animal models of traumatic brain injury.
AB  - After more than 30 years of research and 30 failed clinical trials with as many
      different treatments, progesterone is the first agent to demonstrate robust
      clinical efficacy as a treatment for traumatic brain injuries. It is currently
      being investigated in two, independent phase III clinical trials in hospital
      settings; however, it presents a formidable solubility challenge that has so far
      prevented the identification of a formulation that would be suitable for
      emergency field response use or battlefield situations. Accordingly, we have
      designed and tested a novel series of water-soluble analogues that address this
      critical need. We report here the synthesis of C-20 oxime conjugates of
      progesterone as therapeutic agents for traumatic brain injuries with comparable
      efficacy in animal models of traumatic brain injury and improved solubility and
      pharmacokinetic profiles. Pharmacodynamic analysis reveals that a nonprogesterone
      steroidal analogue may be primarily responsible for the observed activity. 

PMID- 24900480
TI  - Discovery of Selective Small Molecule ROMK Inhibitors as Potential New Mechanism
      Diuretics.
AB  - The renal outer medullary potassium channel (ROMK or Kir1.1) is a putative drug
      target for a novel class of diuretics that could be used for the treatment of
      hypertension and edematous states such as heart failure. An internal high
      throughput screening campaign identified 1,4-bis(4-nitrophenethyl)piperazine (5)
      as a potent ROMK inhibitor. It is worth noting that this compound was identified
      as a minor impurity in a screening hit that was responsible for all of the
      initially observed ROMK activity. Structure-activity studies resulted in
      analogues with improved rat pharmacokinetic properties and selectivity over the
      hERG channel, providing tool compounds that can be used for in vivo
      pharmacological assessment. The featured ROMK inhibitors were also selective
      against other members of the inward rectifier family of potassium channels. 

PMID- 24900481
TI  - A Divergent SAR Study Allows Optimization of a Potent 5-HT2c Inhibitor to a
      Promising Antimalarial Scaffold.
AB  - From the 13 533 chemical structures published by GlaxoSmithKline in 2010, we
      identified 47 quality starting points for lead optimization. One of the most
      promising hits was the TCMDC-139046, a molecule presenting an indoline core,
      which is well-known for its anxiolytic properties by interacting with serotonin
      antagonist receptors 5-HT2. The inhibition of this target will complicate the
      clinical development of these compounds as antimalarials. Herein, we present the
      antimalarial profile of this series and our efforts to avoid interaction with
      this receptor, while maintaining a good antiparasitic potency. By using a double
      divergent structure-activity relationship analysis, we have obtained a novel lead
      compound harboring an indoline core. 

PMID- 24900482
TI  - Targeted kinase selectivity from kinase profiling data.
AB  - Kinase selectivity plays a major role in the design strategy of lead series and
      in the ultimate success of kinase drug discovery programs. Although profiling
      compounds against a large panel of protein kinases has become a standard part of
      modern drug discovery, data accumulated from these kinase panels may be
      underutilized for new kinase projects. We present a method that can be used to
      optimize the selectivity profile of a compound using historical kinase profiling
      data. This method proposes chemical transformations based on pairs of very
      similar compounds, which are both active against a desired target kinase and
      differ in activity against another kinase. We show that these transformations are
      transferable across scaffolds, thus making this tool valuable to exploit kinase
      profiling data for unrelated series of compounds. 

PMID- 24900483
TI  - Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A.
AB  - An in silico screen of the NIH Molecular Library Small Molecule Repository
      (MLSMR) of ~350000 compounds and confirmatory bioassays led to identification of
      chaetochromin A (1) as an inhibitor of botulinum neurotoxin serotype A (BoNT A).
      Subsequent acquisition and testing of analogues of 1 uncovered two compounds,
      talaroderxines A (2) and B (3), with improved activity. These are the first
      fungal metabolites reported to exhibit BoNT/A inhibitory activity. 

PMID- 24900484
TI  - Design of a Potent CB1 Receptor Antagonist Series: Potential Scaffold for
      Peripherally-Targeted Agents.
AB  - Antagonism of cannabinoid-1 (CB1) receptor signaling has been demonstrated to
      inhibit feeding behaviors in humans, but CB1-mediated central nervous system
      (CNS) side effects have halted the marketing and further development of the lead
      drugs against this target. However, peripherally restricted CB1 receptor
      antagonists may hold potential for providing the desired efficacy with reduced
      CNS side effect profiles. In this report we detail the discovery and structure
      activity-relationship analysis of a novel bicyclic scaffold (3) that exhibits
      potent CB1 receptor antagonism and oral activity in preclinical feeding models.
      Optimization of physical properties has led to the identification of analogues
      which are predicted to have reduced CNS exposure and could serve as a starting
      point for the design of peripherally targeted CB1 receptor antagonists. 

PMID- 24900485
TI  - Intestinally Targeted Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitors
      Robustly Suppress Postprandial Triglycerides.
AB  - High DGAT1 expression levels in the small intestine highlight the critical role
      this enzyme plays in nutrient absorption. Identification of inhibitors which
      predominantly inhibit DGAT1 in the gut is an attractive drug discovery strategy
      with anticipated benefits of reduced systemic toxicity. In this report we
      describe our discovery and optimization of DGAT1 inhibitors whose plasma exposure
      is minimized by the action of transporters, including the P-glycoprotein
      transporter. The impact of this unique absorption profile on efficacy in rat and
      dog efficacy models is presented. 

PMID- 24900486
TI  - Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization
      Efforts toward XL518 (GDC-0973).
AB  - The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer
      and is constitutively activated or highly upregulated in many tumor types.
      Mutations associated with upstream pathway components RAS and Raf occur
      frequently and contribute to the oncogenic phenotype through activation of MEK
      and then ERK. Inhibitors of MEK have been shown to effectively block upregulated
      ERK/MAPK signaling in a range of cancer cell lines and have further demonstrated
      early evidence of efficacy in the clinic for the treatment of cancer. Guided by
      structural insight, a strategy aimed at the identification of an optimal
      diphenylamine-based MEK inhibitor with an improved metabolism and safety profile
      versus PD-0325901 led to the discovery of development candidate 1-({3,4-difluoro
      2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin
      3-ol (XL518, GDC-0973) (1). XL518 exhibits robust in vitro and in vivo potency
      and efficacy in preclinical models with sustained duration of action and is
      currently in early stage clinical trials. 

PMID- 24900487
TI  - beta-Lactones Inhibit N-acylethanolamine Acid Amidase by S-Acylation of the
      Catalytic N-Terminal Cysteine.
AB  - The cysteine amidase N-acylethanolamine acid amidase (NAAA) is a member of the N
      terminal nucleophile class of enzymes and a potential target for anti
      inflammatory drugs. We investigated the mechanism of inhibition of human NAAA by
      substituted beta-lactones. We characterized pharmacologically a representative
      member of this class, ARN077, and showed, using high-resolution liquid
      chromatography-tandem mass spectrometry, that this compound forms a thioester
      bond with the N-terminal catalytic cysteine in human NAAA. 

PMID- 24900488
TI  - RXR Partial Agonist CBt-PMN Exerts Therapeutic Effects on Type 2 Diabetes without
      the Side Effects of RXR Full Agonists.
AB  - Treating insulin resistance and type 2 diabetes in rodents, currently known
      retinoid X receptor (RXR) agonists induce significant adverse effects. Here we
      introduce a novel RXR partial agonist CBt-PMN (11b), which shows a potent glucose
      lowering effect and improvements of insulin secretion and glucose tolerance
      without the serious adverse effects caused by RXR full agonists. We suggest that
      RXR partial agonists may be a new class of antitype 2 diabetes drug candidates. 

PMID- 24900489
TI  - Measurement of atropisomer racemization kinetics using segmented flow technology.
AB  - When stable atropisomers are encountered by drug discovery teams, they can have
      important implications due to potential differences in their biological activity,
      pharmacokinetics, and toxicity. Knowledge of an atropisomer's activation
      parameters for interconversion is required to facilitate informed decisions on
      how to proceed. Herein, we communicate the development of a new method for the
      rapid measurement of atropisomer racemization kinetics utilizing segmented flow
      technology. This method leverages the speed, accuracy, low sample requirement,
      safety, and semiautomated nature of flow instrumentation to facilitate the
      acquisition of kinetics data required for experimentally probing atropisomer
      activation parameters. Measured kinetics data obtained for the atropo
      isomerization of AMPA antagonist CP-465021 using segmented flow and traditional
      thermal methods were compared to validate the method. 

PMID- 24900490
TI  - Increasing market exclusivity for new drugs, the cure for what ails us?: patent
      highlight.

PMID- 24900491
TI  - A new era for hepatitis C-new diagnostics tools and new weapons.

PMID- 24900492
TI  - Drug repurposing and the medicinal chemist.
AB  - Drug repurposing is an approach to finding new uses for older drugs and has been
      gaining popularity in recent years. The role of traditional medicinal chemistry
      in the context of these efforts is considered. 

PMID- 24900493
TI  - Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and
      Orally Active CDK4/6 Inhibitors.
AB  - Herein, we describe the discovery of potent and highly selective inhibitors of
      both CDK4 and CDK6 via structure-guided optimization of a fragment-based
      screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered
      efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4
      over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo
      inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft
      model. 

PMID- 24900494
TI  - Synthesis and biochemical evaluation of thiochromanone thiosemicarbazone
      analogues as inhibitors of cathepsin L.
AB  - A series of 36 thiosemicarbazone analogues containing the thiochromanone
      molecular scaffold functionalized primarily at the C-6 position were prepared by
      chemical synthesis and evaluated as inhibitors of cathepsins L and B. The most
      promising inhibitors from this group are selective for cathepsin L and
      demonstrate IC50 values in the low nanomolar range. In nearly all cases, the
      thiochromanone sulfide analogues show superior inhibition of cathepsin L as
      compared to their corresponding thiochromanone sulfone derivatives. Without
      exception, the compounds evaluated were inactive (IC50 > 10000 nM) against
      cathepsin B. The most potent inhibitor (IC50 = 46 nM) of cathepsin L proved to be
      the 6,7-difluoro analogue 4. This small library of compounds significantly
      expands the structure-activity relationship known for small molecule, nonpeptidic
      inhibitors of cathepsin L. 

PMID- 24900495
TI  - Nonsteroidal androgen receptor ligands: versatile syntheses and biological data.
AB  - We report herein a stereoselective and straightforward methodology for the
      synthesis of new androgen receptor ligands with (anti)-agonistic activities.
      Oxygen-nitrogen replacement in bicalutamide-like structures paves the way to the
      disclosure of a new class of analogues, including cyclized/nitrogen-substituted
      derivatives, with promising antiandrogen (or anabolic) activity. 

PMID- 24900496
TI  - Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase
      Inhibitors.
AB  - The HIV pandemic represents one of the most serious diseases to face mankind in
      both a social and economic context, with many developing nations being the worst
      afflicted. Due to ongoing resistance issues associated with the disease, the
      design and synthesis of anti-HIV agents presents a constant challenge for
      medicinal chemists. Utilizing molecular modeling, we have designed a series of
      novel cyclopropyl indole derivatives as HIV non-nucleoside reverse transcriptase
      inhibitors and carried out their preparation. These compounds facilitate a double
      hydrogen bonding interaction to Lys101 and efficiently occupy the hydrophobic
      pockets in the regions of Tyr181/188 and Val179. Several of these compounds
      inhibited HIV replication as effectively as nevirapine when tested in a
      phenotypic assay. 

PMID- 24900497
TI  - Synthesis of New Hydrophilic and Hydrophobic Cobinamides as NO-Independent sGC
      Activators.
AB  - Herein, the synthesis of novel hydrophobic and hydrophilic cobinamides via
      aminolysis of vitamin B12 derivatives that activate soluble guanyl cyclase (sGC)
      is presented. Unlike other sGC regulators, they target the catalytic domain of
      sGC and show higher activity than (CN)2Cbi. 

PMID- 24900498
TI  - Deciphering the Resistance-Counteracting Functions of Ferroquine in Plasmodium
      falciparum-Infected Erythrocytes.
AB  - The aminoquinoline chloroquine (CQ) has been widely used for treating malaria
      since World War II. Resistance to CQ began to spread around 1957 and is now found
      in all malarious areas of the world. CQ resistance is caused by multiple
      mutations in the Plasmodium falciparum chloroquine resistance transporter
      (PfCRT). These mutations result in an increased efflux of CQ from the acidic
      digestive vacuole (DV) to the cytosol of the parasite. This year, we proposed a
      strategy to locate and quantify the aminoquinolines in situ within infected red
      blood cells (iRBCs) using synchrotron based X-ray nanoprobe fluorescence. Direct
      measurements of unlabeled CQ and ferroquine (FQ) (a ferrocene-CQ conjugate,
      extremely active against CQ-resistant strains) enabled us to evidence
      fundamentally different transport mechanisms from the cytosol to the DV between
      CQ and FQ in the CQ-susceptible strain HB3. These results inspired the present
      study of the localization of CQ and FQ in the CQ-resistant strain W2. The
      introduction of the ferrocene core in the lateral side chain of CQ has an
      important consequence: the transporter is unable to efflux FQ from the DV. We
      also found that resistant parasites treated by FQ accumulate a sulfur-containing
      compound, credibly glutathion, in their DV. 

PMID- 24900499
TI  - The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of
      Type 2 Diabetes.
AB  - A structure-activity relationship study of the imidazolyl-beta
      tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3
      antagonist, which demonstrated superior efficacy in a mouse oGTT model. MK-4256
      reduced glucose excursion in a dose-dependent fashion with maximal efficacy
      achieved at doses as low as 0.03 mg/kg po. As compared with glipizide, MK-4256
      showed a minimal hypoglycemia risk in mice. 

PMID- 24900500
TI  - Discovery of HDAC Inhibitors That Lack an Active Site Zn(2+)-Binding Functional
      Group.
AB  - Natural and synthetic histone deacetylase (HDAC) inhibitors generally derive
      their strong binding affinity and high potency from a key functional group that
      binds to the Zn(2+) ion within the enzyme active site. However, this feature is
      also thought to carry the potential liability of undesirable off-target
      interactions with other metalloenzymes. As a step toward mitigating this issue,
      here, we describe the design, synthesis, and structure-activity characterizations
      of cyclic alpha3beta-tetrapeptide HDAC inhibitors that lack the presumed
      indispensable Zn(2+)-binding group. The lead compounds (e.g., 15 and 26) display
      good potency against class 1 HDACs and are active in tissue culture against
      various human cancer cell lines. Importantly, enzymological analysis of 26
      indicates that the cyclic alpha3beta-tetrapeptide is a fast-on/off competitive
      inhibitor of HDACs 1-3 with K i values of 49, 33, and 37 nM, respectively. Our
      proof of principle study supports the idea that novel classes of HDAC inhibitors,
      which interact at the active-site opening, but not with the active site Zn(2+),
      can have potential in drug design. 

PMID- 24900502
TI  - Getting the MAX out of Computational Models: The Prediction of Unbound-Brain and
      Unbound-Plasma Maximum Concentrations.
AB  - The objective of this work was to establish that unbound maximum concentrations
      may be reasonably predicted from a combination of computed molecular properties
      assuming subcutaneous (SQ) dosing. Additionally, we show that the maximum unbound
      plasma and brain concentrations may be projected from a mixture of in vitro
      absorption, distribution, metabolism, excretion experimental parameters in
      combination with computed properties (volume of distribution, fraction unbound in
      microsomes). Finally, we demonstrate the utility of the underlying equations by
      showing that the maximum total plasma concentrations can be projected from the
      experimental parameters for a set of compounds with data collected from clinical
      research. 

PMID- 24900501
TI  - Biotin analogues with antibacterial activity are potent inhibitors of biotin
      protein ligase.
AB  - There is a desperate need to develop new antibiotic agents to combat the rise of
      drug-resistant bacteria, such as clinically important Staphylococcus aureus. The
      essential multifunctional enzyme, biotin protein ligase (BPL), is one potential
      drug target for new antibiotics. We report the synthesis and characterization of
      a series of biotin analogues with activity against BPLs from S. aureus,
      Escherichia coli, and Homo sapiens. Two potent inhibitors with K i < 100 nM were
      identified with antibacterial activity against a panel of clinical isolates of S.
      aureus (MIC 2-16 MUg/mL). Compounds with high ligand efficiency and >20-fold
      selectivity between the isozymes were identified and characterized. The
      antibacterial mode of action was shown to be via inhibition of BPL. The
      bimolecular interactions between the BPL and the inhibitors were defined by
      surface plasmon resonance studies and X-ray crystallography. These findings pave
      the way for second-generation inhibitors and antibiotics with greater potency and
      selectivity. 

PMID- 24900503
TI  - Cracking the code: the promise of epigenetics.

PMID- 24900504
TI  - Rational Design, Synthesis, and SAR of a Novel Thiazolopyrimidinone Series of
      Selective PI3K-beta Inhibitors.
AB  - A novel thiazolopyrimidinone series of PI3K-beta selective inhibitors has been
      identified. This chemotype has provided an excellent tool compound, 18, that
      showed potent growth inhibition in the PTEN-deficient breast cancer cell line MDA
      MB-468 under anchorage-independent conditions, and it also demonstrated
      pharmacodynamic effects and efficacy in a PTEN-deficient prostate cancer PC-3
      xenograft mouse model. 

PMID- 24900505
TI  - Design and synthesis of potent, selective inhibitors of matriptase.
AB  - Matriptase is a member of the type II transmembrane serine protease family.
      Several studies have reported deregulated matriptase expression in several types
      of epithelial cancers, suggesting that matriptase constitutes a potential target
      for cancer therapy. We report herein a new series of slow, tight-binding
      inhibitors of matriptase, which mimic the P1-P4 substrate recognition sequence of
      the enzyme. Preliminary structure-activity relationships indicate that this
      benzothiazole-containing RQAR-peptidomimetic is a very potent inhibitor and
      possesses a good selectivity for matriptase versus other serine proteases. A
      molecular model was generated to elucidate the key contacts between inhibitor 1
      and matriptase. 

PMID- 24900506
TI  - Low Doses of Allyphenyline and Cyclomethyline, Effective against Morphine
      Dependence, Elicit an Antidepressant-like Effect.
AB  - This study demonstrated that cyclomethyline (2) and the corresponding enantiomers
      (R)-(-)-2 and (S)-(+)-2, displaying alpha2C-adrenoreceptor (AR) agonism/alpha2A
      AR antagonism, similarly to allyphenyline (1) and its enantiomers, significantly
      decreased the naloxone-precipitated withdrawal symptoms in mice at very low
      doses. It also highlighted that such positive effects on morphine dependence can
      even be improved by additional serotoninergic 5-HT1A receptor (5-HT1A-R)
      activation. Indeed, 1 or the single (S)-(+)-1, 2, or both its enantiomers, all
      behaving as alpha2C-AR agonists/alpha2A-AR antagonists/5-HT1A-R agonists, alone
      and at the same low dose, improved morphine withdrawal syndrome and exerted a
      potent antidepressant-like effect. Therefore, considering the elevated
      comorbidity between opiate abuse and depressed mood and the benefit of these
      multifunctional compounds to both disorders, it is possible that they prove more
      efficacious and less toxic than a cocktail of drugs in managing opioid addiction.

PMID- 24900507
TI  - Identification of new snake venom metalloproteinase inhibitors using compound
      screening and rational Peptide design.
AB  - The majority of snakebite envenomations in Central America are caused by the
      viperid species Bothrops asper, whose venom contains a high proportion of zinc
      dependent metalloproteinases that play a relevant role in the pathogenesis of
      hemorrhage characteristic of these envenomations. Broad metalloproteinase
      inhibitors, such as the peptidomimetic hydroxamate Batimastat, have been shown to
      inhibit snake venom metalloproteinases (SVMP). However, the difficulty in having
      open public access to Batimastat and similar molecules highlights the need to
      design new inhibitors of SVMPs that could be applied in the treatment of
      snakebite envenomations. We have chosen the SVMP BaP1 as a model to search for
      new inhibitors using different strategies, that is, screening of the Prestwick
      Chemical Library and rational peptide design. Results from these approaches
      provide clues on the structural requirements for efficient BaP1 inhibition and
      pave the way for the design of new inhibitors of SVMP. 

PMID- 24900508
TI  - Synthesis and Agonistic Activity at the GPR35 of 5,6-Dihydroxyindole-2-carboxylic
      Acid Analogues.
AB  - 5,6-Dihydroxyindole-2-carboxylic acid (DHICA), an intermediate of melanin
      synthesis and an eumelanin building block, was recently discovered to be a GPR35
      agonist with moderate potency. Here, we report the synthesis and pharmacological
      characterization of a series of DHICA analogues against GPR35 using both label
      free dynamic mass redistribution and Tango beta-arrestin translocation assays.
      This led to identification of novel GPR35 agonists with improved potency and/or
      having biased agonism. 

PMID- 24900509
TI  - Novel 4-aminoquinoline-pyrimidine based hybrids with improved in vitro and in
      vivo antimalarial activity.
AB  - A class of hybrid molecules consisting of 4-aminoquinoline and pyrimidine were
      synthesized and tested for antimalarial activity against both chloroquine (CQ)
      sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium
      falciparum through an in vitro assay. Eleven hybrids showed better antimalarial
      activity against both CQ-sensitive and CQ-resistant strains of P. falciparum in
      comparison to standard drug CQ. Four molecules were more potent (7-8-fold) than
      CQ in D6 strain, and eight molecules were found to be 5-25-fold more active
      against resistant strain (W2). Several compounds did not show any cytotoxicity up
      to a high concentration (60 MUM), others exhibited mild toxicities, but the
      selective index for the antimalarial activity was very high for most of these
      hybrids. Two compounds selected for in vivo evaluation have shown excellent
      activity (po) in a mouse model of Plasmodium berghei without any apparent
      toxicity. The X-ray crystal structure of one of the compounds was also
      determined. 

PMID- 24900510
TI  - Diaminopyridine-based potent and selective mps1 kinase inhibitors binding to an
      unusual flipped-Peptide conformation.
AB  - Monopolar spindle 1 (Mps1) is an attractive cancer drug target due to the
      important role that it plays in centrosome duplication, the spindle assembly
      checkpoint, and the maintenance of chromosomal stability. A design based on JNK
      inhibitors with an aminopyridine scaffold and subsequent modifications identified
      diaminopyridine 9 with an IC50 of 37 nM. The X-ray structure of 9 revealed that
      the Cys604 carbonyl group of the hinge region flips to form a hydrogen bond with
      the aniline NH group in 9. Further optimization of 9 led to 12 with improved
      cellular activity, suitable pharmacokinetic profiles, and good in vivo efficacy
      in the mouse A549 xenograft model. Moreover, 12 displayed excellent selectivity
      over 95 kinases, indicating the contribution of its unusual flipped-peptide
      conformation to its selectivity. 

PMID- 24900511
TI  - Imidazo[1,2-a]pyridines That Directly Interact with Hepatitis C NS4B: Initial
      Preclinical Characterization.
AB  - A series of imidazo[1,2-a]pyridines which directly bind to HCV Non-Structural
      Protein 4B (NS4B) is described. This series demonstrates potent in vitro
      inhibition of HCV replication (EC50 < 10 nM), direct binding to purified NS4B
      protein (IC50 < 20 nM), and an HCV resistance pattern associated with NS4B
      (H94N/R, V105L/M, F98L) that are unique among reported HCV clinical assets,
      suggestive of the potential for additive or synergistic combination with other
      small molecule inhibitors of HCV replication. 

PMID- 24900512
TI  - Identification and In-Vitro ADME Assessment of a Series of Novel Anti-Malarial
      Agents Suitable for Hit-to-Lead Chemistry.
AB  - Triage of a set of antimalaria hit compounds, identified through high throughput
      screening against the Chloroquine sensitive (3D7) and resistant (Dd2) parasite
      Plasmodium falciparum strains identified several novel chemotypes suitable for
      hit-to-lead chemistry investigation. The set was further refined through
      investigation of their in vitro ADME properties, which identified templates with
      good potential to be developed further as antimalarial agents. One example was
      profiled in an in vivo murine Plasmodium berghei model of malaria infection. 

PMID- 24900513
TI  - Synthesis and functionalization of cyclic sulfonimidamides: a novel chiral
      heterocyclic carboxylic Acid bioisostere.
AB  - An efficient synthesis of aryl substituted cyclic sulfonimidamides designed as
      chiral nonplanar heterocyclic carboxylic acid bioisosteres is described. The
      cyclic sulfonimidamide ring system could be prepared in two steps from a
      trifluoroacetyl protected sulfinamide and methyl ester protected amino acids. By
      varying the amino acid, a range of different C-3 substituted sulfonimidamides
      could be prepared. The compounds could be further derivatized in the aryl ring
      using standard cross-coupling reactions to yield highly substituted cyclic
      sulfonimidamides in excellent yields. The physicochemical properties of the final
      compounds were examined and compared to those of the corresponding carboxylic
      acid and tetrazole derivatives. The unique nonplanar shape in combination with
      the relatively strong acidity (pK a 5-6) and the ease of modifying the chemical
      structure to fine-tune the physicochemical properties suggest that this
      heterocycle can be a valuable addition to the range of available carboxylic acid
      isosteres. 

PMID- 24900514
TI  - Lipophilic Isosteres of a pi-pi Stacking Interaction: New Inhibitors of the Bcl-2
      Bak Protein-Protein Interaction.
AB  - The discovery of new Bcl-2 protein-protein interaction antagonists is described.
      We replaced the northern fragment of ABT737 (pi-pi stacking interactions) with
      structurally simplified hydrophobic cage structures with much reduced
      conformational flexibility and rotational freedom. The binding mode of the
      compounds was elucidated by X-ray crystallography, and the compounds showed
      excellent oral bioavailability and clearance in rat PK studies. 

PMID- 24900515
TI  - 4-quinolones as noncovalent inhibitors of high molecular mass penicillin-binding
      proteins.
AB  - Penicillin-binding proteins (PBPs) are important bacterial enzymes that carry out
      the final steps of bacterial cell wall assembly. Their DD-transpeptidase activity
      accomplishes the essential peptide cross-linking step of the cell wall. To date,
      all attempts to discover effective inhibitors of PBPs, apart from beta-lactams,
      have not led to new antibiotics. Therefore, the need for new classes of efficient
      inhibitors of these enzymes remains. Guided by a computational fragment-based
      docking procedure, carried out on Escherichia coli PBP5, we have designed and
      synthesized a series of 4-quinolones as potential inhibitors of PBPs. We describe
      their binding to the PBPs of E. coli and Bacillus subtilis. Notably, these
      compounds bind quite tightly to the essential high molecular mass PBPs. 

PMID- 24900517
TI  - Potassium channel modulators as possible treatment for pain: patent highlight.

PMID- 24900516
TI  - Discovery of CX-5461, the First Direct and Selective Inhibitor of RNA Polymerase
      I, for Cancer Therapeutics.
AB  - Accelerated proliferation of solid tumor and hematologic cancer cells is linked
      to accelerated transcription of rDNA by the RNA polymerase I (Pol I) enzyme to
      produce elevated levels of rRNA (rRNA). Indeed, upregulation of Pol I, frequently
      caused by mutational alterations among tumor suppressors and oncogenes, is
      required for maintenance of the cancer phenotype and forms the basis for seeking
      selective inhibitors of Pol I as anticancer therapeutics. 2-(4-Methyl
      [1,4]diazepan-1-yl)-5-oxo-5H-7-thia-1,11b-diaza-benzo[c]fluorene-6-carboxylic
      acid (5-methyl-pyrazin-2-ylmethyl)-amide (CX-5461, 7c) has been identified as the
      first potent, selective, and orally bioavailable inhibitor of RNA Pol I
      transcription with in vivo activity in tumor growth efficacy models. The
      preclinical data support the development of CX-5461 as an anticancer drug with
      potential for activity in several types of cancer. 

PMID- 24900518
TI  - JAK Kinase Inhibitors as Possible Treatment for Myeloproliferative Disorders and
      Cancer: Patent Highlight.

PMID- 24900519
TI  - Fatty Acid synthase inhibitors as possible treatment for cancer: patent
      highlight.

PMID- 24900520
TI  - Substituted benzimidazole and imidazopyridine compounds useful as cyp17
      modulators: patent highlight.

PMID- 24900521
TI  - Fused heterocyclic compounds as ion channel modulators: patent highlight.

PMID- 24900522
TI  - Derivatives of heteroarylsulfonamides, their preparation, and their application
      in human therapy: patent highlight.

PMID- 24900523
TI  - Dual Inhibitor of MurD and MurE Ligases from Escherichia coli and Staphylococcus
      aureus.
AB  - MurD and MurE ligases, consecutive enzymes participating in the intracellular
      steps of bacterial peptidoglycan biosynthesis, are important targets for
      antibacterial drug discovery. We have designed, synthesized, and evaluated the
      first d-glutamic acid-containing dual inhibitor of MurD and MurE ligases from
      Escherichia coli and Staphylococcus aureus (IC50 values between 6.4 and 180 MUM)
      possessing antibacterial activity against Gram-positive S. aureus and its
      methicillin-resistant strain (MRSA) with minimal inhibitory concentration (MIC)
      values of 8 MUg/mL. The inhibitor was also found to be noncytotoxic for human
      HepG2 cells at concentrations below 200 MUM. 

PMID- 24900524
TI  - Identification of Hydroxybenzoic Acids as Selective Lactate Receptor (GPR81)
      Agonists with Antilipolytic Effects.
AB  - Following the characterization of the lactate receptor (GPR81), a focused
      screening effort afforded 3-hydroxybenzoic acid 1 as a weak agonist of both GPR81
      and GPR109a (niacin receptor). An examination of structurally similar arylhydroxy
      acids led to the identification of 3-chloro-5-hydroxybenzoic acid 2, a selective
      GPR81 agonist that exhibited favorable in vivo effects on lipolysis in a mouse
      model of obesity. 

PMID- 24900525
TI  - Monitoring the distribution of warfarin in blood plasma.
AB  - Warfarin is an anticoagulant drug extensively used in the treatment and
      prevention of thrombotic disorders. Previous studies have shown that warfarin
      binds extensively to blood plasma proteins and that only a small fraction of the
      drug is unbound and thus available for therapeutic function. Both warfarin's
      narrow therapeutic window and the susceptibility of anticoagulant function to
      patient-dependent factors necessitate regular monitoring. In this study, we have
      shown that the lifetimes for each of the various bound and free forms of the drug
      in blood plasma can be quantified in situ by time-correlated single-photon
      counting fluorescence spectroscopy over the clinically significant concentration
      range. A relationship between the blood coagulation and the distribution of
      fluorescence lifetimes was observed. The in situ detection of clinically relevant
      concentrations of warfarin in its respective bound and unbound forms could
      provide a prognostic tool for use in patient treatment. 

PMID- 24900527
TI  - Antimicrobial Activity of Adenine-Based Inhibitors of NAD(+)-Dependent DNA
      Ligase.
AB  - The relationship between enzyme inhibition and antimicrobial potency of adenine
      based NAD(+)-dependent DNA ligase (LigA) inhibitors was investigated using a
      strain of the Gram-negative pathogen Haemophilus influenzae lacking its major
      AcrAB-TolC efflux pump and the Gram-positive pathogen Streptococcus pneumoniae.
      To this end, biochemical inhibitors not mediating their antibacterial mode of
      action (MOA) via LigA were removed from the analysis. In doing so, a significant
      number of compounds were identified that acted via inhibition of LigA in S.
      pneumoniae but not in H. influenzae, despite being inhibitors of both isozymes.
      Deviations from the line correlating antimicrobial and biochemical potencies of
      LigA inhibitors with the correct MOA were observed for both species. These
      deviations, usually corresponding to higher MIC/IC50 ratios, were attributed to
      varying compound permeance into the cell. 

PMID- 24900526
TI  - Target-Activated Prodrugs (TAPs) for the Autoregulated Inhibition of MMP12.
AB  - We describe a prodrug concept in which the target enzyme MMP12 produces its own
      inhibitor in a two-step activation procedure. By using an MMP12-specific peptide
      sequence and a known sulfonamide drug integrated in the backbone, the active
      inhibitor is released upon enzyme cleavage. In in vitro experiments, we present
      proof of concept that the activation proceeds with useful kinetics. The approach
      is highly selective over the closely related MMP8. If applied in vivo in the
      future, these prodrugs might release the active entity in a highly specific
      manner only at such sites where enzyme activity resides. 

PMID- 24900528
TI  - Creation of readily accessible and orally active analogue of cortistatin a.
AB  - Syntheses of structurally simplified analogues of cortistatin A (1), a novel
      antiangiogenic steroidal alkaloid from Indonesian marine sponge, and their
      biological activities were investigated. The analogues were designed by
      considering the 3-D structure of 1. Compound 30, in which the isoquinoline moiety
      was appended to the planar tetracyclic core structure, showed potent
      antiproliferative activity against human umbilical vein endothelial cells
      (HUVECs) together with high selectivity and also showed in vivo antiangiogenic
      activity and significant antitumor effect by oral administration. 

PMID- 24900529
TI  - Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside
      Reverse Transcriptase Inhibitors.
AB  - We identified a novel class of aryl-substituted triazine compounds as potent non
      nucleoside reverse transcriptase inhibitors (NNRTIs) during a high-throughput
      screening campaign that evaluated more than 200000 compounds for antihuman
      immunodeficiency virus (HIV) activity using a cell-based full replication assay.
      Herein, we disclose the optimization of the antiviral activity in a cell-based
      assay system leading to the discovery of compound 27, which possessed excellent
      potency against wild-type HIV-1 (EC50 = 0.2 nM) as well as viruses bearing Y181C
      and K103N resistance mutations in the reverse transcriptase gene. The X-ray
      crystal structure of compound 27 complexed with wild-type reverse transcriptase
      confirmed the mode of action of this novel class of NNRTIs. Introduction of a
      chloro functional group in the pyrazole moiety dramatically improved hERG and CYP
      inhibition profiles, yielding highly promising leads for further development. 

PMID- 24900531
TI  - Four lessons from global health drug discovery: medicine for an ailing industry?
AB  - In recent years, the pharmaceutical industry has faced many challenges to its
      business model, undergoing tremendous change and turmoil to survive. Are there
      any lessons to be drawn from drug discovery focused on Global Health, where there
      is little market incentive? 

PMID- 24900530
TI  - Lipidated peptidomimetics with improved antimicrobial activity.
AB  - We report a series of lipidated alpha-AApeptides that mimic the structure and
      function of natural antimicrobial lipopeptides. Several short lipidated alpha
      AApeptides show broad-spectrum activity against a range of clinically related
      Gram-positive and Gram-negative bacteria as well as fungus. Their antimicrobial
      activity and selectivity are comparable or even superior to the clinical
      candidate pexiganan as well as previously reported linear alpha-AApeptides. The
      further development of lipidated alpha-AApeptides will lead to a new class of
      antibiotics to combat drug resistance. 

PMID- 24900532
TI  - Bromodomains: are readers right for epigenetic therapy?
AB  - There is intense interest in the development of small molecule inhibitors of the
      acetyl-lysine-reading bromodomain protein module. These inhibitors represent a
      way of interfering therapeutically in epigenetic processes, and there are
      currently two bromodomain inhibitors in clinical trials. The success of these
      compounds rests on safety aspects of epigenetic target modulation being
      addressed. 

PMID- 24900533
TI  - Substituted pyridines as sodium channel blockers: patent highlight.

PMID- 24900534
TI  - Cyclopropyl-spiro-piperidines Useful as Sodium Channel Blockers: Patent
      Highlight.

PMID- 24900536
TI  - Inhibitors of LRRK2 as Treatment for Parkinson's Disease: Patent Highlight.

PMID- 24900535
TI  - Hepatitis C virus protease inhibitors: patent highlight.

PMID- 24900537
TI  - Prostaglandin e2 synthase-1 inhibitors as potential treatment for osteoarthritis:
      patent highlight.

PMID- 24900538
TI  - Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA
      Inhibitors.
AB  - Trk receptor tyrosine kinases have been implicated in cancer and pain. A crystal
      structure of TrkA with AZ-23 (1a) was obtained, and scaffold hopping resulted in
      two 5/6-bicyclic series comprising either imidazo[4,5-b]pyridines or purines.
      Further optimization of these two fusion series led to compounds with
      subnanomolar potencies against TrkA kinase in cellular assays. Antitumor effects
      in a TrkA-driven mouse allograft model were demonstrated with compounds 2d and
      3a. 

PMID- 24900539
TI  - Discovery of AM-1638: A Potent and Orally Bioavailable GPR40/FFA1 Full Agonist.
AB  - GPR40 (FFA1) is a G-protein-coupled receptor, primarily expressed in pancreatic
      islets, the activation of which elicits increased insulin secretion only in the
      presence of elevated glucose levels. A potent, orally bioavailable small molecule
      GPR40 agonist is hypothesized to be an effective antidiabetic posing little or no
      risk of hypoglycemia. We recently reported the discovery of AMG 837 (1), a potent
      partial agonist of GPR40. Herein, we present the optimization from the GPR40
      partial agonist 1 to the structurally and pharmacologically distinct GPR40 full
      agonist AM-1638 (21). Moreover, we demonstrate the improved in vivo efficacy that
      GPR40 full agonist 21 exhibits in BDF/DIO mice as compared to partial agonist 1. 

PMID- 24900541
TI  - Quinolinyl Pyrimidines: Potent Inhibitors of NDH-2 as a Novel Class of Anti-TB
      Agents.
AB  - NDH-2 is an essential respiratory enzyme in Mycobacterium tuberculosis (Mtb),
      which plays an important role in the physiology of Mtb. Herein, we present a
      target-based effort to identify a new structural class of inhibitors for NDH-2.
      High-throughput screening of the AstraZeneca corporate collection resulted in the
      identification of quinolinyl pyrimidines as the most promising class of NDH-2
      inhibitors. Structure-activity relationship studies showed improved enzyme
      inhibition (IC50) against the NDH-2 target, which in turn translated into
      cellular activity against Mtb. Thus, the compounds in this class show a good
      correlation between enzyme inhibition and cellular potency. Furthermore, early
      ADME profiling of the best compounds showed promising results and highlighted the
      quinolinyl pyrimidine class as a potential lead for further development. 

PMID- 24900540
TI  - Irreversible 4-Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's
      Disease.
AB  - A new series of potent TG2 inhibitors are reported that employ a 4
      aminopiperidine core bearing an acrylamide warhead. We establish the structure
      activity relationship of this new series and report on the transglutaminase
      selectivity and in vitro ADME properties of selected compounds. We demonstrate
      that the compounds do not conjugate glutathione in an in vitro setting and have
      superior plasma stability over our previous series. 

PMID- 24900542
TI  - Crystal structure and specific binding mode of sisomicin to the bacterial
      ribosomal decoding site.
AB  - Sisomicin with an unsaturated sugar ring I displays better antibacterial activity
      than other structurally related aminoglycosides, such as gentamicin, tobramycin,
      and amikacin. In the present study, we have confirmed by X-ray analyses that the
      binding mode of sisomicin is basically similar but not identical to that of the
      related compounds having saturated ring I. A remarkable difference is found in
      the stacking interaction between ring I and G1491. While the typical saturated
      ring I with a chair conformation stacks on G1491 through CH/pi interactions, the
      unsaturated ring I of sisomicin with a partially planar conformation can share
      its pi-electron density with G1491 and fits well within the A-site helix. 

PMID- 24900543
TI  - Macrocyclic peptoid-Peptide hybrids as inhibitors of class I histone
      deacetylases.
AB  - We report the design, synthesis, and biological evaluation of the first
      macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The
      compounds selectively inhibit human class I HDAC isoforms in vitro, with no
      inhibition of the tubulin deacetylase activity associated with class IIb HDAC6 in
      cultured Jurkat cells. Compared to the natural product apicidin (1), one
      inhibitor (compound 10) showed equivalent potency against K-562 cells, but was
      more cytoselective across a panel of cancer cell lines. 

PMID- 24900544
TI  - Discovery of DS-8108b, a Novel Orally Bioavailable Renin Inhibitor.
AB  - A novel orally bioavailable renin inhibitor, DS-8108b (5), showing potent renin
      inhibitory activity and excellent in vivo efficacy is described. We report herein
      the synthesis and pharmacological effects of 5 including renin inhibitory
      activity in vitro, suppressive effects of ex vivo plasma renin activity (PRA) in
      cynomolgus monkey, pharmacokinetic data, and blood pressure-lowering effects in
      an animal model. Compound 5 demonstrated inhibitory activities toward human renin
      (IC50 = 0.9 nM) and human and monkey PRA (IC50 = 1.9 and 6.3 nM, respectively).
      Oral administration of single doses of 3 and 10 mg/kg of 5 in cynomolgus monkey
      on pretreatment with furosemide led to dose-dependent significant reductions in
      ex vivo PRA and sustained lowering of mean arterial blood pressure for more than
      12 h. 

PMID- 24900545
TI  - Identification of an Adamantyl Azaquinolone JNK Selective Inhibitor.
AB  - 3-[4-((1S,2S,3R,5S,7S)-5-Hydroxyadamantan-2-ylcarbamoyl)benzyl]-4-oxo-1-phenyl
      1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (4) was identified
      as a novel, druglike and selective quinolone pan JNK inhibitor. In this
      communication, some of the structure-activity relationship of the azaquinolone
      analogues leading to 4 is discussed. The focus is on how changes at the amide
      functionality affected the biochemical potency, cellular potency, metabolic
      properties, and solubility of this class of JNK inhibitors. Optimization of these
      properties led to the identification of the adamantyl analogue, 4. 4 achieved
      proof of mechanism in both rat and mouse TNF-alpha challenge models. 

PMID- 24900546
TI  - Symmetric kv1.5 blockers discovered by focused screening.
AB  - Guided by computational methods, a set of 1920 compounds were selected from the
      AstraZeneca corporate collection and screened for Kv1.5 activity. To facilitate
      rapid generation of structure-activity relationships, special attention was given
      to selecting subsets of structurally similar molecules by using a maximum common
      substructure similarity-based procedure. The focused screen hit rate was
      relatively high (12%). More importantly, a structural series featured by the
      symmetric 1,2-diphenylethane-1,2-diamine substructure was identified as potent
      Kv.1.5 blockers. The property profile for the series is shown to meet stringent
      lead-optimization criteria, providing a springboard for the development of a new
      and safe treatment for atrial fibrillation. 

PMID- 24900547
TI  - Fluorescent Human EP3 Receptor Antagonists.
AB  - Exchange of the lipophilc part of ortho-substituted cinnamic acid lead structures
      with different small molecule fluorophoric moieties via a dimethylene spacer
      resulted in hEP3R ligands with affinities in the nanomolar concentration range.
      Synthesized compounds emit fluorescence in the blue, green, and red range of
      light and have been tested concerning their potential as a pharmacological tool.
      hEP3Rs were visualized by confocal laser scanning microscopy on HT-29 cells, on
      murine kidney tissues, and on human brain tissues and functionally were
      characterized as antagonists on human platelets. Inhibition of PGE2 and collagen
      induced platelet aggregation was measured after preincubation with novel hEP3R
      ligands. The pyryllium-labeled ligand 8 has been shown as one of the most
      promising structures, displaying a useful fluorescence and highly affine hEP3R
      antagonists. 

PMID- 24900548
TI  - Using medicinal chemistry to solve an old medical mystery.
AB  - The logic behind the traditional medicinal chemistry technique of designing a
      synthetic enzyme substrate to mimic a natural one is used to uncover the identity
      of the unknown cause of two legacy industrial diseases by comparing the reported
      symptoms to two side effects of a modern synthetic. 

PMID- 24900549
TI  - Metabolites of the pyrimidine amine preladenant as adenosine a2a receptor
      antagonists.

PMID- 24900550
TI  - HDAC Inhibitors as Targeted Treatment of Frontotemporal Lobar Degeneration.

PMID- 24900551
TI  - Modulators of the GPR119 Receptor for the Treatment of Metabolic Syndrome.

PMID- 24900552
TI  - Novel Amino-Nicotinamide Derivatives as Modulators of KCNQ2/3 Potassium Channels.

PMID- 24900553
TI  - Multifunctional radical quenchers for the treatment of mitochondrial dysfunction.

PMID- 24900554
TI  - Modulators of mitochondrial protein import.

PMID- 24900555
TI  - Novel pyrroles as nicotinic acetylcholine receptor modulators.

PMID- 24900556
TI  - Treatment of Obesity and Related Disorders with Acetyl-CoA Carboxylase
      Inhibitors.

PMID- 24900557
TI  - Spleen Tyrosine Kinase Inhibitors (SYK) as Potential Treatment for Autoimmune and
      Inflammatory Disorders: Patent Highlight.

PMID- 24900558
TI  - Insulin-like growth factor-1 receptor inhibitors: a potential cancer treatment:
      patent highlight.

PMID- 24900559
TI  - Novel 2-aminobenzamides as potential orally active antithrombotic agents.
AB  - In an effort to develop potent antithrombotic agents, a series of novel 2
      aminobenzamide derivatives were synthesized and screened for their in vivo
      antithrombotic activity. Among the 23 compounds tested, compound (8g) showed the
      most promising antithrombotic activity, which was comparable with clinically used
      aspirin or warfarin, but at variance with these standard drugs, 8g did not
      exhibit the increased bleeding time, suggesting its potential as a novel
      antithrombotic agent. 

PMID- 24900561
TI  - Magnolia Extract, Magnolol, and Metabolites: Activation of Cannabinoid CB2
      Receptors and Blockade of the Related GPR55.
AB  - The bark of Magnolia officinalis is used in Asian traditional medicine for the
      treatment of anxiety, sleeping disorders, and allergic diseases. We found that
      the extract and its main bioactive constituents, magnolol and honokiol, can
      activate cannabinoid (CB) receptors. In cAMP accumulation studies, magnolol
      behaved as a partial agonist (EC50 = 3.28 MUM) with selectivity for the CB2
      subtype, while honokiol was less potent showing full agonistic activity at CB1
      and antagonistic properties at CB2. We subsequently synthesized the major
      metabolites of magnolol and found that tetrahydromagnolol (7) was 19-fold more
      potent than magnolol (EC50 CB2 = 0.170 MUM) exhibiting high selectivity versus
      CB1. Additionally, 7 behaved as an antagonist at GPR55, a CB-related orphan
      receptor (K B = 13.3 MUM, beta-arrestin translocation assay). Magnolol and its
      metabolites may contribute to the biological activities of Magnolia extract via
      the observed mechanisms of action. Furthermore, the biphenylic compound magnolol
      provides a simple novel lead structure for the development of agonists for CB
      receptors and antagonists for the related GPR55. 

PMID- 24900560
TI  - Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New
      Potency-Enhancing Interactions.
AB  - A series of aryl hydroxamates recently have been disclosed as irreversible
      inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a
      role in schizophrenia and other psychiatric and neurological disorders. The
      utilization of structure-activity relationships (SAR) in conjunction with X-ray
      crystallography led to the discovery of hydroxamate 4, a disubstituted analogue
      that has a significant potency enhancement due to a novel interaction with KAT
      II. The use of k inact/K i to assess potency was critical for understanding the
      SAR in this series and for identifying compounds with improved pharmacodynamic
      profiles. 

PMID- 24900563
TI  - Structural permutation of potent cytotoxin, polytheonamide B: discovery of
      cytotoxic Peptide with altered activity.
AB  - Polytheonamide B (1) is an ion-channel forming natural peptide with a d,l
      alternating 48 amino acid sequence, which is an exceedingly potent cytotoxin. We
      recently designed and synthesized a simplified dansylated polytheonamide mimic 2,
      in which six amino acid residues were modified from 1, and demonstrated that 2
      emulated the functions of 1. Here we report a comprehensive structure-activity
      relationship study of substructures of 2. A unified synthetic strategy was
      developed for highly automated syntheses of 13 peptide sequences of 27 to 39
      amino acid residues, and the artificial 37-mer peptide 6 was discovered to be
      significantly more toxic than the other 12 compounds toward P388 mouse leukemia
      cells (IC50 = 3.7 nM). Ion exchange activity experiments of 6 using the liposome
      and P388 cells both demonstrated that 6 did not possess ion-channel activity,
      strongly suggesting that 6 exerted its potent cytoxicity through a distinct mode
      of action from 1 and 2. 

PMID- 24900562
TI  - Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and
      antidepressant activity.
AB  - Herein, we describe the discovery of inhibitors of norepinephrine (NET) and
      dopamine (DAT) transporters with reduced activity relative to serotonin
      transporters (SERT). Two compounds, 8b and 21a, along with nomifensine were
      tested in a rodent receptor occupancy study and demonstrated dose-dependent
      displacement of radiolabeled NET and DAT ligands. These compounds were
      efficacious in a rat forced swim assay (model of depression) and also had
      activity in rat spontaneous locomotion assay. 

PMID- 24900564
TI  - Identification of Tetrahydropyrido[4,3-d]pyrimidine Amides as a New Class of
      Orally Bioavailable TGR5 Agonists.
AB  - Takeda G-protein-coupled receptor 5 (TGR5) represents an exciting biological
      target for the potential treatment of diabetes and metabolic syndrome. A new
      class of high-throughput screening (HTS)-derived tetrahydropyrido[4,3
      d]pyrimidine amide TGR5 agonists is disclosed. We describe our effort to identify
      an orally available agonist suitable for assessment of systemic TGR5 agonism.
      This effort resulted in identification of 16, which had acceptable potency and
      pharmacokinetic properties to allow for in vivo assessment in dog. A key aspect
      of this work was the calibration of human and dog in vitro assay systems that
      could be linked with data from a human ex vivo peripheral blood monocyte assay
      that expresses receptor at endogenous levels. Potency from the human in vitro
      assay was also found to correlate with data from an ex vivo human whole blood
      assay. This calibration exercise provided confidence that 16 could be used to
      drive plasma exposures sufficient to test the effects of systemic activation of
      TGR5. 

PMID- 24900566
TI  - Tuning RNA Interference by Enhancing siRNA/PAZ Recognition.
AB  - Chemically modified siRNAs were synthesized to enhance the corresponding
      silencing activities. The introduced modifications endowed siRNAs with high
      silencing effect, long RNAi persistence, and better serum resistance. Theoretical
      data allowed us to correlate the observed siRNAs interfering performance with the
      peculiar interactions with PAZ. 

PMID- 24900565
TI  - Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and
      Imidazopyridine Derivatives.
AB  - Sepsis, an acute inflammatory disease, remains the most common cause of death in
      intensive care units. A series of benzimidazole and imidazopyridine derivatives
      were synthesized and screened for anti-inflammatory activities, and the
      imidazopyridine series showed excellent inhibition of the expression of
      inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13,
      X14, and X15 inhibited TNF-alpha and IL-6 release in a dose-dependent manner, and
      X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a
      significant protection against LPS-induced septic death in mouse models.
      Together, these data present a series of new imidazopyridines with potential
      therapeutic effects in acute inflammatory diseases. 

PMID- 24900567
TI  - Discovery of a Highly Selective, Brain-Penetrant Aminopyrazole LRRK2 Inhibitor.
AB  - The modulation of LRRK2 kinase activity by a selective small molecule inhibitor
      has been proposed as a potentially viable treatment for Parkinson's disease. By
      using aminopyrazoles as aniline bioisosteres, we discovered a novel series of
      LRRK2 inhibitors. Herein, we describe our optimization effort that resulted in
      the identification of a highly potent, brain-penetrant aminopyrazole LRRK2
      inhibitor (18) that addressed the liabilities (e.g., poor solubility and
      metabolic soft spots) of our previously disclosed anilino-aminopyrimidine
      inhibitors. In in vivo rodent PKPD studies, 18 demonstrated good brain exposure
      and engendered significant reduction in brain pLRRK2 levels post-ip
      administration. The strategies of bioisosteric substitution of aminopyrazoles for
      anilines and attenuation of CYP1A2 inhibition described herein have potential
      applications to other drug discovery programs. 

PMID- 24900568
TI  - Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through
      Structure-Based Drug Design.
AB  - PI3K, AKT, and mTOR are key kinases from PI3K signaling pathway being extensively
      pursued to treat a variety of cancers in oncology. To search for a structurally
      differentiated back-up candidate to PF-04691502, which is currently in phase I/II
      clinical trials for treating solid tumors, a lead optimization effort was carried
      out with a tricyclic imidazo[1,5]naphthyridine series. Integration of structure
      based drug design and physical properties-based optimization yielded a potent and
      selective PI3K/mTOR dual kinase inhibitor PF-04979064. This manuscript discusses
      the lead optimization for the tricyclic series, which both improved the in vitro
      potency and addressed a number of ADMET issues including high metabolic clearance
      mediated by both P450 and aldehyde oxidase (AO), poor permeability, and poor
      solubility. An empirical scaling tool was developed to predict human clearance
      from in vitro human liver S9 assay data for tricyclic derivatives that were AO
      substrates. 

PMID- 24900569
TI  - Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC
      0349.
AB  - Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in
      human tumors and tumor cell lines, indicating that these protein kinases may be
      attractive therapeutic targets for treating cancer. Optimization of advanced lead
      1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a
      potent and selective ATP-competitive inhibitor of mTOR. GDC-0349 demonstrates
      pathway modulation and dose-dependent efficacy in mouse xenograft cancer models. 

PMID- 24900570
TI  - De novo prediction of p-glycoprotein-mediated efflux liability for druglike
      compounds.
AB  - P-glycoprotein (Pgp) is capable of recognizing and transporting a wide range of
      chemically diverse compounds in vivo. Overcoming Pgp-mediated efflux can
      represent a significant challenge when penetration into the central nervous
      system is required or within the context of developing anticancer therapies.
      While numerous in silico models have been developed to predict Pgp-mediated
      efflux, these models rely on training sets and are best suited to make
      interpolations. Therefore, it is desirable to develop ab initio models that can
      be used to predict efflux liabilities. Herein, we present a de novo method that
      can be used to predict Pgp-mediated efflux potential for druglike compounds. A
      model, which correlates the computed solvation free energy differences obtained
      in water and chloroform with Pgp-mediated efflux (in logarithmic scale), was
      successful in predicting Pgp efflux ratios for a wide range of chemically diverse
      compounds with a R(2) and root-mean-square error of 0.65 and 0.29, respectively. 

PMID- 24900571
TI  - Imidazopyridine-Based Fatty Acid Synthase Inhibitors That Show Anti-HCV Activity
      and in Vivo Target Modulation.
AB  - Potent imidazopyridine-based inhibitors of fatty acid synthase (FASN) are
      described. The compounds are shown to have antiviral (HCV replicon) activities
      that track with their biochemical activities. The most potent analogue (compound
      19) also inhibits rat FASN and inhibits de novo palmitate synthesis in vitro
      (cell-based) as well as in vivo. 

PMID- 24900572
TI  - Discovery of HSD-621 as a Potential Agent for the Treatment of Type 2 Diabetes.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion
      of inactive glucocorticoid cortisone to its active form, cortisol. The
      glucocorticoid receptor (GR) signaling pathway has been linked to the
      pathophysiology of diabetes and metabolic syndrome. Herein, the structure
      activity relationship of a series of piperazine sulfonamide-based 11beta-HSD1
      inhibitors is described. (R)-3,3,3-Trifluoro-2-(5-(((R)-4-(4-fluoro-2
      (trifluoromethyl)phenyl)-2-methylpiperazin-1-yl)sulfonyl)thiophen-2-yl)-2
      hydroxypropanamide 18a (HSD-621) was identified as a potent and selective 11beta
      HSD1 inhibitor and was ultimately selected as a clinical development candidate.
      HSD-621 has an attractive overall pharmaceutical profile and demonstrates good
      oral bioavailability in mouse, rat, and dog. When orally dosed in C57/BL6 diet
      induced obesity (DIO) mice, HSD-621 was efficacious and showed a significant
      reduction in both fed and fasting glucose and insulin levels. Furthermore, HSD
      621 was well tolerated in drug safety assessment studies. 

PMID- 24900573
TI  - Visible Light Controlled Release of Anticancer Drug through Double Activation of
      Prodrug.
AB  - We designed and synthesized a novel double activatable prodrug system (drug
      linker-deactivated photosensitizer), containing a photocleavable aminoacrylate
      linker and a deactivated photosensitizer, to achieve the spatiotemporally
      controlled release of parent drugs using visible light. Three prodrugs of CA-4,
      SN-38, and coumarin were prepared to demonstrate the activation of deactivated
      photosensitizer by cellular esterase and the release of parent drugs by visible
      light (540 nm) via photounclick chemistry. Among these prodrugs, nontoxic
      coumarin prodrug was used to quantify the release of parent drug in live cells.
      About 99% coumarin was released from the coumarin prodrug after 24 h of
      incubation with MCF-7 cells followed by irradiation with low intensity visible
      light (8 mW/cm(2)) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed
      cancer cells as effectively as free drugs after the double activation. 

PMID- 24900574
TI  - Synthesis and antiplasmodial and antimycobacterial evaluation of new
      nitroimidazole and nitroimidazooxazine derivatives.
AB  - The synthesis and antiplasmodial and antimycobacterial evaluation of two new
      series of nitroimidazole and nitroimidazooxazine derivatives is described. The
      majority of these compounds, especially hybrids 9d, 9f, and 14b, exhibited potent
      activity against the chloroquine-resistant K1 strain of Plasmodium falciparum.
      Furthermore, a notable number from the tetrazole series were significantly more
      active against M. tuberculosis than kanamycin, a standard TB drug. 

PMID- 24900575
TI  - Biological evaluation of new largazole analogues: alteration of macrocyclic
      scaffold with click chemistry.
AB  - We report the design, synthesis, and biological evaluation of a new series of
      largazole analogues in which a 4-methylthiazoline moiety was replaced with a
      triazole and tetrazole ring, respectively. Compound 7 bearing a tetrazole ring
      was identified to show much better selectivity for HDAC1 over HDAC9 than
      largazole (10-fold). This work could serve as a foundation for further
      exploration of selective HDAC inhibitors using a largazole molecular scaffold. 

PMID- 24900576
TI  - Solvent Selection for Insoluble Ligands, a Challenge for Biological Assay
      Development: A TNF-alpha/SPD304 Study.
AB  - Many active compounds may be excluded from biological assays due to their low
      aqueous solubility. In this study, a simple method for the determination of the
      solubility of compounds containing aromatic rings is proposed. In addition to
      DMSO, five organic solvents for screening experiments of TNF-alpha inhibitors
      were explored. DMSO and PEG3350 were the most suitable for both protein stability
      and ligand-binding experiments. In addition, glycerol is a promising solvent for
      the screening of other compounds for which it might provide acceptable
      solubilization, due to its strong tendency to preserve the protein. Moreover, a
      fluorescence binding assay was developed using the TNF-alpha/SPD304 system, and a
      K d of 5.36 +/- 0.21 MUM was determined. The results of this study could be used
      for the future screening of potential TNF-alpha inhibitors, while the protocols
      developed in this work could be applied to other proteins. 

PMID- 24900577
TI  - Rapid Determination of Ionization Constants (pK a) by UV Spectroscopy Using 96
      Well Microtiter Plates.
AB  - We have developed a methodology that enables for the rapid measurement of
      ionization constants (pK a) of series of compounds by UV spectrophotometry. This
      protocol, which is straightforward to set up, takes advantage of the sensitivity
      of UV spectroscopy and the throughput enabled by the 96-well microplate (as
      opposed to the use of 1 cm quartz cuvette). The compounds, in stock solutions in
      DMSO, are dissolved in several aqueous buffer solutions directly in the
      microtiter plate, allowing the simultaneous determination of the UV spectra as a
      function of pH. Further treatment of the data provides the pK a values in a
      medium-throughput manner. The pK a values of 11 new antitrypanosomal dibasic
      compounds were determined using this methodology. 

PMID- 24900579
TI  - Nexus between protein-ligand affinity rank-ordering, biophysical approaches, and
      drug discovery.
AB  - The confluence of computational and biophysical methods to accurately rank-order
      the binding affinities of small molecules and determine structures of
      macromolecular complexes is a potentially transformative advance in the work flow
      of drug discovery. This viewpoint explores the impact that advanced computational
      methods may have on the efficacy of small molecule drug discovery and
      optimization, particularly with respect to emerging fragment-based methods. 

PMID- 24900578
TI  - WalK, the Path towards New Antibacterials with Low Potential for Resistance
      Development.
AB  - Resistance to antibiotics used in the treatment of bacterial infectious diseases
      is a global health problem. More than a decade ago, two-component systems such as
      WalKR were proposed as ideal targets for the development of new antibiotics.
      Biochemical screens for WalKR inhibitors using compound libraries have identified
      many hits, some of which were shown to have non-specific effects. The recently
      published structures of the S. mutans and B. subtilis WalK provide the
      opportunity to study inhibitors of WalK autophosphorylation at the atomic level
      and means to design compounds with improved specificity and affinity using a
      structure-based approach. 

PMID- 24900580
TI  - Fighting Obesity and Metabolic Disorders with MGAT-2 Inhibitors.

PMID- 24900581
TI  - Fighting Obesity and Metabolic Disorders with DGAT-1 Inhibitors.

PMID- 24900582
TI  - Anabaseine analogues as modulators of nicotinic acetylcholine receptor.

PMID- 24900583
TI  - Arylthioamides as H2S Donors: l-Cysteine-Activated Releasing Properties and
      Vascular Effects in Vitro and in Vivo.
AB  - A small library of arylthioamides 1-12 was easily synthesized, and their H2S
      releasing properties were evaluated both in the absence or in the presence of an
      organic thiol such as l-cysteine. A number of arylthioamides (1-3 and 7) showed a
      slow and l-cysteine-dependent H2S-releasing mechanism, similar to that exhibited
      by the reference slow H2S-releasing agents, such as diallyl disulfide (DADS) and
      the phosphinodithioate derivative GYY 4137. Compound 1 strongly abolished the
      noradrenaline-induced vasoconstriction in isolated rat aortic rings and
      hyperpolarized the membranes of human vascular smooth muscle cells in a
      concentration-dependent fashion. Finally, a significant reduction of the systolic
      blood pressure of anesthetized normotensive rats was observed after its oral
      administration. Altogether these results highlighted the potential of
      arylthioamides 1-3 and 7 as H2S-donors for basic studies, and for the rational
      design/development of promising pharmacotherapeutic agents to treat
      cardiovascular diseases. 

PMID- 24900584
TI  - Synthesis and Evaluation of Quinazolone Derivatives as a New Class of c-KIT G
      Quadruplex Binding Ligands.
AB  - The c-KIT G-quadruplex structures are a novel class of attractive targets for the
      treatment of gastrointestinal stromal tumor (GIST). Herein, a series of new
      quinazolone derivatives with the expansion of unfused aromatic ring system were
      designed and synthesized. Subsequent biophysical studies demonstrated that the
      derivatives with adaptive scaffold could effectively bind to and stabilize c-KIT
      G-quadruplexes with good selectivity against duplex DNA. More importantly, these
      ligands further inhibited the transcription and expression of c-KIT gene and
      exhibited significant cytotoxicity on the GIST cell line HGC-27. Overall, these
      quinazolone derivatives represent a new class of promising c-KIT G-quadruplex
      ligands. The experimental results have also reinforced the idea of inhibition of
      c-KIT expression through targeting c-KIT G-quadruplex DNA. 

PMID- 24900585
TI  - Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of
      E2F1 in Lung Cancer Cells.
AB  - Aberration in cell cycle has been shown to be a common occurrence in lung cancer,
      and cell cycle inhibitor represents an effective therapeutic strategy. In this
      study, we test the effects of a natural macrocyclic depsipeptide largazole on
      lung cancer cells and report that this compound potently inhibits the
      proliferation and clonogenic activity of lung cancer cells but not normal
      bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up
      regulation of the expression of cyclin-dependent kinase inhibitor p21.
      Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a
      proteasomal degradation of E2F1, leading to suppression of E2F1 function in lung
      cancer but not normal bronchial epithelial cells. Because E2F1 is overexpressed
      in lung cancer tumor samples, these data indicate that largazole is an E2F1
      targeting cell cycle inhibitor, which bears therapeutic potentials for this
      malignant neoplasm. 

PMID- 24900586
TI  - Non-cross-bridged tetraazamacrocyclic chelator for stable (64)cu-based
      radiopharmaceuticals.
AB  - N-mono/dimethylated TE2A tetraazamacrocycles (MM-TE2A and DM-TE2A) were
      synthesized in high yields. Both Cu-MM/DM-TE2A complexes showed increased kinetic
      stability compared to that of Cu-TE2A, whereas Cu-DM-TE2A showed even higher in
      vitro stability than that of Cu-ECB-TE2A. MM-TE2A and DM-TE2A were quantitatively
      radiolabeled with (64)Cu ions and showed rapid clearance from the body to emerge
      as a potential efficient bifunctional chelator. 

PMID- 24900587
TI  - Discovery of DF-461, a Potent Squalene Synthase Inhibitor.
AB  - We report the development of a new trifluoromethyltriazolobenzoxazepine series of
      squalene synthase inhibitors. Structure-activity studies and pharmacokinetics
      optimization on this series led to the identification of compound 23 (DF-461),
      which exhibited potent squalene synthase inhibitory activity, high hepatic
      selectivity, excellent rat hepatic cholesterol synthesis inhibitory activity, and
      plasma lipid lowering efficacy in nonrodent repeated dose studies. 

PMID- 24900588
TI  - Design and Synthesis of 4-(4-Benzoylaminophenoxy)phenol Derivatives As Androgen
      Receptor Antagonists.
AB  - We report the design and synthesis of novel 4-(4-benzoylaminophenoxy)phenol
      derivatives that bind to the androgen receptor (AR) ligand-binding domain and
      exhibit potent androgen-antagonistic activity. Compound 22 is one of the most
      potent of these derivatives, inhibiting the dihydrotestosterone-promoted growth
      of SC-3 cell line bearing wild-type AR (IC50 0.75 MUM), LNCaP cell line bearing
      T877A-mutated AR (IC50 0.043 MUM), and 22Rv1 cell line bearing H874Y-mutated AR
      (IC50 0.22 MUM). Structure-activity relationship studies confirmed that the
      pharmacophore of these novel AR antagonists is distinct from the nitro- or cyano
      substituted anilide substructure of other nonsteroidal AR antagonists. This novel
      pharmacophore is expected to provide a basis for designing new antiprostate
      cancer agents. 

PMID- 24900589
TI  - Discovery of Clinical Candidate GSK1842799 As a Selective S1P1 Receptor Agonist
      (Prodrug) for Multiple Sclerosis.
AB  - To develop effective oral treatment for multiple sclerosis (MS), we discovered a
      series of alkyl-substituted biaryl amino alcohols as selective S1P1 modulators.
      One exemplar is (S)-2-amino-2-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,3,4
      thiadiazol-2-yl)propan-1-ol (10, GSK1842799). Upon phosphorylation, the compound
      (10-P) showed subnanomole S1P1 agonist activity with >1000* selectivity over
      S1P3. The alcohol 10 demonstrated good oral bioavailability and rapid in vivo
      conversion to 10-P. Dosed orally at 0.1 mg/kg, 10 significantly reduced blood
      lymphocyte counts 6 h postdose, and at 3 mg/kg, 10 achieved efficacy equivalent
      to FTY720 in the mouse EAE model of MS. Further pharmacokinetic/pharmacodynamic
      (PK/PD) study with cynomolgus monkeys indicated that, after oral dosing of 10 at
      3.8 mg/kg, the active phosphate reached plasma levels that are comparable to FTY
      720 phosphate (FTY-P) revealed in human clinical pharmacokinetics studies. On the
      basis of the favorable in vitro ADME and in vivo PK/PD properties as well as
      broad toxicology evaluations, compound 10 (GSK1842799) was selected as a
      candidate for further clinical development. 

PMID- 24900590
TI  - Identification of a Novel and Selective Series of Itk Inhibitors via a Template
      Hopping Strategy.
AB  - Inhibition of Itk potentially constitutes a novel, nonsteroidal treatment for
      asthma and other T-cell mediated diseases. In-house kinase cross-screening
      resulted in the identification of an aminopyrazole-based series of Itk
      inhibitors. Initial work on this series highlighted selectivity issues with
      several other kinases, particularly AurA and AurB. A template-hopping strategy
      was used to identify a series of aminobenzothiazole Itk inhibitors, which
      utilized an inherently more selective hinge binding motif. Crystallography and
      modeling were used to rationalize the observed selectivity. Initial exploration
      of the SAR around this series identified potent Itk inhibitors in both enzyme and
      cellular assays. 

PMID- 24900592
TI  - Identification of 1-[4-Benzyloxyphenyl)-but-3-enyl]-1H-azoles as New Class of
      Antitubercular and Antimicrobial Agents.
AB  - A series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1H-azoles has been identified as
      potent antitubercular agents against Mycobacterium tuberculosis. Synthesis of
      compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl
      cyclopropyl methanols followed by nucleophilic attack of the azoles on the
      carbocation intermediates. Several of the compounds 26, 34, and 36 exhibited
      significant antitubercular activities with MIC value as low as 1.56, 1.56, and
      0.61 MUg/mL, respectively, comparable to many standard drugs. These compounds
      were also screened against other strains of bacteria and fungi, and few of them
      showed good antifungal activity against A. fumigatus, responsible for lung
      infection. 

PMID- 24900591
TI  - A structurally simplified analogue of geldanamycin exhibits neuroprotective
      activity.
AB  - The syntheses of a structurally simplified geldanamycin analogue 2 and two
      related compounds are described. Compound 2 conferred cytoprotection and quenched
      ROS and lipid peroxidation in a dose-dependent manner in Friedreich's ataxia
      (FRDA) lymphocytes at low micromolar concentrations. It also prevented ROS
      induced damage of cellular lipid membranes and maintained the mitochondrial
      membrane potential of FRDA lymphocytes. In addition, 2 did not inhibit Hsp90 when
      tested at micromolar concentrations, exhibited no cytotoxicity, and afforded
      neuroprotection to differentiated SH-SY5Y cells under conditions of Abeta-induced
      cell toxicity. 

PMID- 24900593
TI  - Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical
      Development.
AB  - We recently reported the discovery of GSK2606414 (1), a selective first in class
      inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK),
      which inhibited PERK activation in cells and demonstrated tumor growth inhibition
      in a human tumor xenograft in mice. In continuation of our drug discovery
      program, we applied a strategy to decrease inhibitor lipophilicity as a means to
      improve physical properties and pharmacokinetics. This report describes our
      medicinal chemistry optimization culminating in the discovery of the PERK
      inhibitor GSK2656157 (6), which was selected for advancement to preclinical
      development. 

PMID- 24900594
TI  - Design, Synthesis, and Biological Evaluation of Novel Conformationally
      Constrained Inhibitors Targeting EGFR.
AB  - This letter describes the construction of conformationally constrained
      quinazoline analogues. Structure-activity relationship studies led to the
      identification of the lead compound 9n . Compound 9n exhibits effective in vitro
      activity against A431(WT,overexpression) and H1975([L858R/T790M]) cancer cell
      lines but is significantly less effective against EGFR negative cancer cell lines
      (SW620, A549, and K562). Compound 9n was also assessed for potency in enzymatic
      assays and in vivo antitumor studies. The results indicated that 9n is a potent
      kinase inhibitor against both wild-type and T790M mutant EGFR kinase. Meanwhile,
      an oral administration of 9n at a dose of 200 mg/kg produced a considerable
      antitumor effect in a A431 xenograft model, as compared to gefitinib. A
      preliminary pharmacokinetic study of 9n also indicates it has good
      pharmacokinetic properties, and therefore, it is a good starting point for
      further development. 

PMID- 24900595
TI  - Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity.
AB  - Here, we describe the selection and optimization of a chemical series active in
      both a full-length and a fragment-based Huntington's disease (HD) assay. Twenty
      four thousand small molecules were screened in a phenotypic HD assay, identifying
      a series of compounds bearing a 3-hydroxy-3-trifluoromethylpyrazole moiety as
      able to revert the toxicity induced by full-length mutant Htt by up to 50%. A
      chemical exploration around the series led to the identification of compound 4f,
      which demonstrated to be active in a Htt171-82Q rat primary striatal neuron assay
      and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2
      mice, in which it was well-tolerated and showed a positive effect on body weight
      and a positive trend in preventing ventricular volume enlargment. These studies
      provide strong rationale for further testing the potential benefits of 3-hydroxy
      3-trifluoromethylpyrazoles in treating HD. 

PMID- 24900597
TI  - Sphingosine-1-phosphate (S1P) Receptor Modulators Provide Potential for Diverse
      Treatments.

PMID- 24900596
TI  - Synthesis and Biological Evaluation of the First Example of NO-Donor Histone
      Deacetylase Inhibitor.
AB  - The NO-donor histone deacetylase inhibitor 2, formally obtained by joining
      Entinostat 1, a moderately selective Class I histone deacetylases (HDACs)
      inhibitor, to a 4-(methylaminomethyl)furoxan-3-carbonitrile scaffold, is
      described and its preliminary biological profile discussed. This hybrid regulates
      Classes I and II HDACs. Nitric oxide (NO) released by the compound activates
      soluble guanylate cyclase (sGC), causing Class II nuclear shuttling and chromatin
      modifications, with consequences on gene expression. The hybrid affects a number
      of micro-RNAs not modulated by its individual components; it promotes myogenic
      differentiation, inducing the formation of larger myotubes with significantly
      more nuclei per fiber, in a more efficient manner than the 1:1 mixture of its two
      components. The hybrid is an example of a new class of NO-donor HDACs now being
      developed, which should be of interest for treating a number of diseases. 

PMID- 24900598
TI  - Endothelial lipase inhibitors for the treatment of atherosclerosis and
      cardiovascular disorders.

PMID- 24900599
TI  - New synthetic enediynes and their conjugates may provide effective treatment for
      cancer.

PMID- 24900600
TI  - Benzoxazine Derivatives As CRAC Modulators.

PMID- 24900601
TI  - N-[4-(1H-Pyrazolo[3,4-B]pyrazin-6yl)-phenyl]-sulonamides and Their Use As
      Pharmaceuticals.

PMID- 24900602
TI  - Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and
      Selective A2B Adenosine Receptor Antagonists.
AB  - We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as
      a novel family of (nonxanthine) A2B receptor antagonists that exhibit an
      unusually high selectivity profile. The Biginelli-based hit optimization process
      enabled a thoughtful exploration of the structure-activity and structure
      selectivity relationships for this chemotype, enabling the identification of
      ligands that combine structural simplicity with excellent hA2B AdoR affinity and
      remarkable selectivity profiles. 

PMID- 24900603
TI  - Identification and optimization of an aminoalcohol-carbazole series with
      antimalarial properties.
AB  - Recent observations on the emergence of artemisinin resistant parasites have
      highlighted the need for new antimalarial treatments. An HTS campaign led to the
      identification of the 1-(1-aminopropan-2-ol)carbazole analogues as potent hits
      against Plasmodium falciparum K1 strain. The SAR study and optimization of early
      ADME and physicochemical properties direct us to the selection of a late lead
      compound that shows good efficacy when orally administrated in the in vivo P.
      berghei mouse model. 

PMID- 24900604
TI  - Discovery of Octahydroindenes as PAR1 Antagonists.
AB  - Octahydroindene was identified as a novel scaffold for protease activated
      receptor 1 (PAR1) antagonists. Herein, the 2-position (C2) was explored for
      structure-activity relationship (SAR) studies. Compounds 14, 19, and 23b showed
      IC50 values of 1.3, 8.6, and 2.7 nM in a PAR1 radioligand binding assay,
      respectively, and their inhibitory activities on platelet activation were
      comparable to that of vorapaxar in a platelet rich plasma (PRP) aggregation
      assay. This series of compounds showed high potency and no significant
      cytotoxicity; however, the compounds were metabolically unstable in both human
      and rat liver microsomes. Current research efforts are focused on optimizing the
      compounds to improve metabolic stability and physicochemical properties as well
      as potency. 

PMID- 24900605
TI  - Fluorine Scanning by Nonselective Fluorination: Enhancing Raf/MEK Inhibition
      while Keeping Physicochemical Properties.
AB  - A facile methodology effective in obtaining a set of compounds monofluorinated at
      various positions (fluorine scan) by chemical synthesis is reported. Direct and
      nonselective fluorination reactions of our lead compound 1a and key intermediate
      2a worked efficiently to afford a total of six monofluorinated derivatives. All
      of the derivatives kept their physicochemical properties compared with the lead
      1a and one of them had enhanced Raf/MEK inhibitory activity. Keeping
      physicochemical properties could be considered a benefit of monofluorinated
      derivatives compared with chlorinated derivatives, iodinated derivatives,
      methylated derivatives, etc. This key finding led to the identification of
      compound 14d, which had potent tumor growth inhibition in a xenograft model,
      excellent PK profiles in three animal species, and no critical toxicity. 

PMID- 24900606
TI  - Improved Cav2.2 Channel Inhibitors through a gem-Dimethylsulfone Bioisostere
      Replacement of a Labile Sulfonamide.
AB  - We report the investigation of sulfonamide-derived Cav2.2 inhibitors to address
      drug-metabolism liabilities with this lead class of analgesics. Modification of
      the benzamide substituent provided improvements in both potency and selectivity.
      However, we discovered that formation of the persistent 3
      (trifluoromethyl)benzenesulfonamide metabolite was an endemic problem in the
      sulfonamide series and that the replacement of the center aminopiperidine
      scaffold failed to prevent this metabolic pathway. This issue was eventually
      addressed by application of a bioisostere strategy. The new gem-dimethyl sulfone
      series retained Cav2.2 potency without the liability of the circulating
      sulfonamide metabolite. 

PMID- 24900607
TI  - Potent oxazolidinone antibacterials with heteroaromatic C-ring substructure.
AB  - Novel oxazolidinone analogues bearing a condensed heteroaromatic ring as the C
      ring substructure were synthesized as candidate antibacterial agents. Analogues
      16 and 21 bearing imidazo[1,2-a]pyridine and 18 and 23 bearing
      [1,2,4]triazolo[1,5-a]pyridine as the C-ring had excellent in vitro antibacterial
      activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin
      resistant Enterococcus faecalis (VRE), and penicillin-resistant Streptococcus
      pneumoniae (PRSP). They also showed promising therapeutic effects in a mouse
      model of lethal infection. Preliminary safety data (inhibitory effects on
      cytochrome P450 isoforms and monoamine oxidases) were satisfactory. Further
      evaluation of 18 and 23 is ongoing. 

PMID- 24900608
TI  - Chemical Probe Identification Platform for Orphan GPCRs Using Focused Compound
      Screening: GPR39 as a Case Example.
AB  - Orphan G protein-coupled receptors (oGPCRs) are a class of integral membrane
      proteins for which endogenous ligands or transmitters have not yet been
      discovered. Transgenic animal technologies have uncovered potential roles for
      many of these oGPCRs, providing new targets for the treatment of various
      diseases. Understanding signaling pathways of oGPCRs and validating these
      receptors as potential drug targets requires the identification of chemical probe
      compounds to be used in place of endogenous ligands to interrogate these
      receptors. A novel chemical probe identification platform was created in which
      GPCR-focused libraries were screened against sets of oGPCR targets, with a goal
      of discovering fit-for-purpose chemical probes for the more druggable members of
      the set. Application of the platform to a set of oGPCRs resulted in the discovery
      of the first reported small molecule agonists for GPR39, a receptor implicated in
      the regulation of insulin secretion and preservation of beta cells in the
      pancreas. Compound 1 stimulated intracellular calcium mobilization in recombinant
      and native cells in a GPR39-specific manner but did not potentiate glucose
      stimulated insulin secretion in human islet preparations. 

PMID- 24900609
TI  - Validation of Reactivity Descriptors to Assess the Aromatic Stacking within the
      Tyrosine Gate of FimH.
AB  - Antagonists of the FimH adhesin, a protein almost universally present at the
      extremity of type-1 fimbriae expressed by Escherichia coli, have been abundantly
      in the spotlight as alternative treatments of urinary tract infections. The
      antagonists function as bacterial antiadhesives through highly specific alpha-d
      mannose binding in a charged and polar pocket at the tip of the FimH lectin
      domain and by the stacking of alkyl or aromatic moieties substituted on the
      mannose with two tyrosine residues (Tyr48 and Tyr137) at the entrance of the
      mannose-binding pocket. Using high-resolution crystal data, interaction energies
      are calculated for the different observed aromatic stacking modes between the
      tyrosines and the antagonist. The dispersion component of the interaction energy
      correlates with the observed electron density. The quantum chemical reactivity
      descriptors local hardness and polarizability were successfully validated as
      prediction tools for ligand affinity in the tyrosine gate of FimH and therefore
      have potential for rapid drug screening. 

PMID- 24900610
TI  - Structures of human acetylcholinesterase bound to dihydrotanshinone I and
      territrem B show peripheral site flexibility.
AB  - Acetylcholinesterase is a critical enzyme that regulates neurotransmission by
      degrading the neurotransmitter acetylcholine in synapses of the nervous system.
      It is an important target for both therapeutic drugs that treat Alzheimer's
      disease and chemical warfare agents that cripple the nervous system and cause
      death through paralysis. The enzyme has both catalytic and peripheral sites to
      which inhibitors may bind. Structures of recombinant human acetylcholinesterase
      in complex with the natural product inhibitors dihydrotanshinone I and territrem
      B reveal dihydrotanshinone I binding that is specific to only the peripheral site
      and territrem B binding that spans both sites and distorts the protein backbone
      in the peripheral site. These inhibitors may function as important molecular
      templates for therapeutics used for treatment of disease and protection against
      nerve agents. 

PMID- 24900611
TI  - Adamantyl derivative as a potent inhibitor of Plasmodium FK506 binding protein
      35.
AB  - FKBP35, FK506 binding protein family member, in Plasmodium species displays a
      canonical peptidyl-prolyl isomerase (PPIase) activity and is intricately involved
      in the protein folding process. Inhibition of PfFKBP35 by FK506 or its analogues
      were shown to interfere with the in vitro growth of Plasmodium falciparum. In
      this study, we have synthesized adamantyl derivatives, Supradamal (SRA/4a) and
      its analogues SRA1/4b and SRA2/4c, which demonstrate submicromolar inhibition of
      Plasmodium falciparum FK506 binding domain 35 (FKBD35) PPIase activity. SRA and
      its analogues not only inhibit the in vitro growth of Plasmodium falciparum 3D7
      strain but also show stage specific activity by inhibiting the trophozoite stage
      of the parasite. SRA/4a also inhibits the Plasmodium vivax FKBD35 PPIase activity
      and our crystal structure of PvFKBD35 in complex with the SRA provides structural
      insights in achieving selective inhibition against Plasmodium FKBPs. 

PMID- 24900612
TI  - Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising
      Route for Treating Glioblastoma.
AB  - The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically
      important mediator of tumor growth and therapeutic resistance in GBM. Thus, for
      poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas,
      which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will
      be of significant importance. Herein, we report a most potent, small molecule,
      nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3
      protein (K D = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer
      stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its
      downstream transcriptional targets at low nM concentrations. Moreover, in vivo,
      31 exhibited blood-brain barrier permeability, potently controlled glioma tumor
      growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates
      the power of STAT3 inhibitors for the treatment of BTSCs and validates the
      therapeutic efficacy of a STAT3 inhibitor for GBM clinical application. 

PMID- 24900613
TI  - Discovery of triazine mimetics as potent antileishmanial agents.
AB  - The World Health Organization has classified the leishmaniasis as a major
      tropical disease. The discovery of new compounds for leishmaniasis is therefore a
      pressing concern for the anti-infective research program. We have synthesized 19
      compounds of triazine dimers as novel antileishmanial agents. Most of the
      synthesized derivatives exhibited better activity against intracellular
      amastigotes (IC50 ranging from 0.77 to 10.32 MUM) than the control, pentamidine
      (IC50 = 13.68 MUM), and are not toxic to Vero cells. Compounds 14 and 15 showed
      significant in vivo inhibition of 74.41% and 62.64%, respectively, in L.
      donovani/hamster model. Moreover, expansion of Th1-type and suppression of Th2
      type immune responses proved that compound 14 stimulates mouse macrophages to
      prevent the progression of leishmania parasite. The molecular docking studies
      involving PTR1 protein PDB further validated the concepts involved in the design
      of these compounds. Among the investigated analogues, compound 14 has emerged as
      the potential one to enlarge the scope of the study. 

PMID- 24900616
TI  - New inhibitors of cytomegalovirus DNA polymerase.

PMID- 24900614
TI  - Preparative microfluidic electrosynthesis of drug metabolites.
AB  - In vivo, a drug molecule undergoes its first chemical transformation within the
      liver via CYP450-catalyzed oxidation. The chemical outcome of the first pass
      hepatic oxidation is key information to any drug development process.
      Electrochemistry can be used to simulate CYP450 oxidation, yet it is often
      confined to the analytical scale, hampering product isolation and full
      characterization. In an effort to replicate hepatic oxidations, while retaining
      high throughput at the preparative scale, microfluidic technology and
      electrochemistry are combined in this study by using a microfluidic
      electrochemical cell. Several commercial drugs were subjected to continuous-flow
      electrolysis. They were chosen for their various chemical reactivity: their
      metabolites in vivo are generated via aromatic hydroxylation, alkyl oxidation,
      glutathione conjugation, or sulfoxidation. It is demonstrated that such
      metabolites can be synthesized by flow electrolysis at the 10 to 100 mg scale,
      and the purified products are fully characterized. 

PMID- 24900617
TI  - Inhibition of CK2: An Attractive Therapeutic Target for Cancer Treatment.

PMID- 24900618
TI  - Influenza RNA-Dependent RNA Polymerase (RdRp) Inhibitors: Potential New Therapy
      for Influenza Treatment.

PMID- 24900619
TI  - Diphenylpropane Derivatives as Agonist of PPAR Nuclear Receptors.

PMID- 24900620
TI  - Synthesis of Novel 3,5-Disubstituted-2-oxindole Derivatives As Antitumor Agents
      against Human Nonsmall Cell Lung Cancer.
AB  - This study was aimed at investigating the antitumor activity of novel 2-oxindole
      derivatives against a well-characterized human nonsmall cell lung cancer (NSCLC)
      cell line. Test compounds produced an antiproliferative activity in the low
      micromolar/submicromolar range of concentrations and significantly induced
      typical apoptotic morphology with cell shrinkage, nuclear condensation and
      fragmentation, and rupture of cells into debris in a relatively low percentage of
      A549 cells. Cell cycle arrest occurred at the G1/S phase (1a and 2), and Akt
      phosphorylation was significantly inhibited at Thr308 and Ser473. The most active
      compound (1a) has an IC50 6-fold lower than the Akt inhibitor, perifosine. These
      data suggest that the new compounds may be cytostatic and may have maximum
      clinical effects in NSCLC patients who do not respond to EGFR inhibitors. These
      findings prompt us to further explore the oxindole structure as leading scaffold
      to design new molecules with potent antitumor activity against NSCLC. 

PMID- 24900621
TI  - Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase
      Inhibitors.
AB  - Matriptase belongs to trypsin-like serine proteases involved in matrix
      remodeling/degradation, growth regulation, survival, motility, and cell
      morphogenesis. Herein, we report a structure-based approach, which led to the
      discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as
      potent and selective matriptase inhibitors. Co-crystal structures of selected
      compounds in complex with matriptase supported compound designing. Additionally,
      WaterMap analyses indicated the possibility of occupying a distinct pocket within
      the catalytic domain, exploration of which resulted in >100-fold improvement in
      potency. Co-crystal structure of 10 with matriptase revealed critical
      interactions leading to potent target inhibition and selectivity against other
      serine proteases. 

PMID- 24900622
TI  - Probing the Binding Site of Bile Acids in TGR5.
AB  - TGR5 is a G-protein-coupled receptor (GPCR) mediating cellular responses to bile
      acids (BAs). Although some efforts have been devoted to generate homology models
      of TGR5 and draw structure-activity relationships of BAs, none of these studies
      has hitherto described how BAs bind to TGR5. Here, we present an integrated
      computational, chemical, and biological approach that has been instrumental to
      determine the binding mode of BAs to TGR5. As a result, key residues have been
      identified that are involved in mediating the binding of BAs to the receptor.
      Collectively, these results provide new hints to design potent and selective TGR5
      agonists. 

PMID- 24900623
TI  - Stapled Vasoactive Intestinal Peptide (VIP) Derivatives Improve VPAC2 Agonism and
      Glucose-Dependent Insulin Secretion.
AB  - Agonists of vasoactive intestinal peptide receptor 2 (VPAC2) stimulate glucose
      dependent insulin secretion, making them attractive candidates for the treatment
      of hyperglycaemia and type-II diabetes. Vasoactive intestinal peptide (VIP) is an
      endogenous peptide hormone that potently agonizes VPAC2. However, VIP has a short
      serum half-life and poor pharmacokinetics in vivo and is susceptible to
      proteolytic degradation, making its development as a therapeutic agent
      challenging. Here, we investigated two peptide cyclization strategies,
      lactamisation and olefin-metathesis stapling, and their effects on VPAC2 agonism,
      peptide secondary structure, protease stability, and cell membrane permeability.
      VIP analogues showing significantly enhanced VPAC2 agonist potency, glucose
      dependent insulin secretion activity, and increased helical content were
      discovered; however, neither cyclization strategy appeared to effect proteolytic
      stability or cell permeability of the resulting peptides. 

PMID- 24900624
TI  - Exploring the chemical space of multitarget ligands using aligned self-organizing
      maps.
AB  - Design of multitarget drugs and polypharmacological compounds has become popular
      during the past decade. However, the main approach to design such compounds is to
      link two selective ligands via a flexible linker. Although such chimeric ligands
      often have reasonable potency in vitro, the in vivo efficacy is low due to high
      molecular weight, low ligand efficiency, and poor pharmacokinetic profile. We
      developed an unprecedented in silico approach for fragment-based design of
      multitarget ligands. It relies on superposition of the chemical spaces related to
      the affinity on single targets represented by self-organizing maps. We used this
      approach for screening of molecular fragments, which bind to the enzymes 5
      lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH). Using STD-NMR and
      activity-based assays, we were able to identify fragments binding to both
      targets. Furthermore, we were able to expand one of the fragments to a potent
      dual inhibitor bearing a reasonable molecular weight (MW = 446) and high affinity
      to both targets (IC50 of 0.03 MUM toward 5-LO and 0.17 MUM toward sEH). 

PMID- 24900625
TI  - Design and Discovery of 2-Arylquinazolin-4-ones as Potent and Selective
      Inhibitors of Tankyrases.
AB  - Tankyrases (TNKSs) are poly(ADP-ribose)polymerases (PARPs) that are overexpressed
      in several clinical cancers. They regulate elongation of telomeres, regulate the
      Wnt system, and are essential for the function of the mitotic spindle. A set of 2
      arylquinazolin-4-ones has been designed and identified as potent and selective
      TNKS inhibitors, some being more potent and selective than the lead inhibitor
      XAV939, with IC50 = 3 nM vs. TNKS-2. Methyl was preferred at the 8-position and
      modest bulk at the 4-position of the 2-phenyl group; electronic effects and H
      bonding were irrelevant, but charge in the 4'-substituent must be avoided.
      Molecular modeling facilitated initial design of the compounds and
      rationalization of the SAR of binding into the nicotinamide-binding site of the
      target enzymes. These compounds have potential for further development into
      anticancer drugs. 

PMID- 24900627
TI  - Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse
      Transcriptase.
AB  - In a continuing study of potent bifunctional anti-HIV agents, we rationally
      designed a novel chimeric inhibitor utilizing thymidine (THY) and a TMC
      derivative (a diarylpyrimidine NNRTI) linked via a polymethylene linker (ALK).
      The nucleoside, 5'-hydrogen-phosphonate (H-phosphonate), and 5'-triphosphate
      forms of this chimeric inhibitor (THY-ALK-TMC) were synthesized and the antiviral
      activity profiles were evaluated at the enzyme and cellular level. The nucleoside
      triphosphate (11) and the H-phosphonate (10) derivatives inhibited RT
      polymerization with an IC50 value of 6.0 and 4.3 nM, respectively. Additionally,
      chimeric nucleoside (9) and H-phosphonate (10) derivatives reduced HIV
      replication in a cell-based assay with low nanomolar antiviral potencies. 

PMID- 24900626
TI  - Multifunctional cholinesterase and amyloid Beta fibrillization modulators.
      Synthesis and biological investigation.
AB  - In order to identify novel Alzheimer's modifying pharmacological tools, we
      developed bis-tacrines bearing a peptide moiety for specific interference with
      surface sites of human acetylcholinesterase (hAChE) binding amyloid-beta (Abeta).
      Accordingly, compounds 2a-c proved to be inhibitors of hAChE catalytic and
      noncatalytic functions, binding the catalytic and peripheral sites, interfering
      with Abeta aggregation and with the Abeta self-oligomerization process (2a).
      Compounds 2a-c in complex with TcAChE span the gorge with the bis-tacrine system,
      and the peptide moieties bulge outside the gorge in proximity of the peripheral
      site. These moieties are likely responsible for the observed reduction of hAChE
      induced Abeta aggregation since they physically hamper Abeta binding to the
      enzyme surface. Moreover, 2a was able to significantly interfere with Abeta self
      oligomerization, while 2b,c showed improved inhibition of hAChE-induced Abeta
      aggregation. 

PMID- 24900628
TI  - Antitumor potential of conjugable valinomycins bearing hydroxyl sites: in vitro
      studies.
AB  - Following our pioneering studies on the direct and efficient introduction of
      derivatizable hydroxyl handles into the valinomycin (VLM, 1) structure, a K(+)
      ionophore with potent antitumor activity, the ensuing conjugable analogues
      (HyVLMs 2, 3, and 4) have herein been compared to the parent macrocycle for their
      potential antiproliferative effects on a panel of cancer cell lines, namely,
      human MCF-7, A2780, and HepG2, as well as rat C6 cells. On the basis of IC50
      values, we find that hydroxyl analogues 3 and 4 are only moderately less active
      than 1, while analogue 2 experiences a heavily diminished activity.
      Cytofluorimetric analyses of MCF-7 cells treated with HyVLMs suggest that the
      latter depolarize mitochondria, thus retaining the typical VLM behavior. It is
      likely that C6 cells, for which the exceptionally potent cytotoxicity of VLM has
      never reported previously, follow the same fate, as evidenced by alteration of
      mitochondrial morphology upon incubation with each ionophore. 

PMID- 24900629
TI  - Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM
      Kinase Inhibitors.
AB  - Proviral insertion of Moloney virus (PIM) 1, 2, and 3 kinases are
      serine/threonine kinases that normally function in survival and proliferation of
      hematopoietic cells. As high expression of PIM1, 2, and 3 is frequently observed
      in many human malignancies, including multiple myeloma, non-Hodgkins lymphoma,
      and myeloid leukemias, there is interest in determining whether selective PIM
      inhibition can improve outcomes of these human cancers. Herein, we describe our
      efforts toward this goal. The structure guided optimization of a singleton high
      throughput screening hit in which the potency against all three PIM isoforms was
      increased >10,000-fold to yield compounds with pan PIM K is < 10 pM, nanomolar
      cellular potency, and in vivo activity in an acute myeloid leukemia Pim-dependent
      tumor model is described. 

PMID- 24900630
TI  - Synthesis and in vitro and in vivo pharmacological evaluation of new 4
      aminoquinoline-based compounds.
AB  - A new class of 4-aminoquinolines was synthesized and evaluated in vitro for
      antiplasmodial activity against both the chloroquine-sensitive (3D7) and 
      resistant (K1 and W2) strains. The most active compounds 3c-3e had acceptable
      cytotoxicity but showed strong inhibition toward a panel of cytochrome P450
      enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they
      had moderate half-life (4-6 h) and low oral bioavailability. The front runner
      compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei
      infected mice following oral administration (5 mg/kg), achieving reduction of
      parasitemia population by 47% on day 7. 

PMID- 24900631
TI  - Discovery and in Vivo Evaluation of Potent Dual CYP11B2 (Aldosterone Synthase)
      and CYP11B1 Inhibitors.
AB  - Aldosterone is a key signaling component of the renin-angiotensin-aldosterone
      system and as such has been shown to contribute to cardiovascular pathology such
      as hypertension and heart failure. Aldosterone synthase (CYP11B2) is responsible
      for the final three steps of aldosterone synthesis and thus is a viable
      therapeutic target. A series of imidazole derived inhibitors, including clinical
      candidate 7n, have been identified through design and structure-activity
      relationship studies both in vitro and in vivo. Compound 7n was also found to be
      a potent inhibitor of 11beta-hydroxylase (CYP11B1), which is responsible for
      cortisol production. Inhibition of CYP11B1 is being evaluated in the clinic for
      potential treatment of hypercortisol diseases such as Cushing's syndrome. 

PMID- 24900632
TI  - Fragment-based discovery of 6-azaindazoles as inhibitors of bacterial DNA ligase.
AB  - Herein we describe the application of fragment-based drug design to bacterial DNA
      ligase. X-ray crystallography was used to guide structure-based optimization of a
      fragment-screening hit to give novel, nanomolar, AMP-competitive inhibitors. The
      lead compound 13 showed antibacterial activity across a range of pathogens. Data
      to demonstrate mode of action was provided using a strain of S. aureus,
      engineered to overexpress DNA ligase. 

PMID- 24900633
TI  - Structure-based design of 2-aminopyridine oxazolidinones as potent and selective
      tankyrase inhibitors.
AB  - Aberrant activation of the Wnt pathway has been implicated in the development and
      formation of many cancers. TNKS inhibition has been shown to antagonize Wnt
      signaling via Axin stabilization in APC mutant colon cancer cell lines. We
      employed structure-based design to identify a series of 2-aminopyridine
      oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited
      good enzyme and cell potency as well as selectivity over other PARP isoforms. Co
      crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS
      reveal an induced-pocket binding mode that does not involve interactions with the
      nicotinamide binding pocket. Oral dosing of lead compounds 3 and 4 resulted in
      significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse
      tumor PD model. 

PMID- 24900634
TI  - Design and Synthesis of Peptide YY Analogues with C-terminal Backbone Amide-to
      Ester Modifications.
AB  - Peptide YY (PYY) is a gut hormone that activates the G protein-coupled
      neuropeptide Y (NPY) receptors, and because of its appetite reducing actions, it
      is evaluated as an antiobesity drug candidate. The C-terminal tail of PYY is
      crucial for activation of the NPY receptors. Here, we describe the design and
      preparation of a series of PYY(3-36) depsipeptide analogues, in which backbone
      amide-to-ester modifications were systematically introduced in the C-terminal.
      Functional NPY receptor assays and circular dichroism revealed that the psi(CONH)
      bonds at positions 30-31 and 33-34 are particularly important for receptor
      interaction and that the latter is implicated in Y2 receptor selectivity. 

PMID- 24900637
TI  - Nanomaterials for (Nano)medicine.
AB  - Next generation nanomedicine will rely on innovative nanomaterials capable of
      unprecedented performance. Which ones are the most promising candidates for a
      medicinal chemist? 

PMID- 24900635
TI  - Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of
      Pathologies Associated with Necroptosis.
AB  - Potent inhibitors of RIP1 kinase from three distinct series, 1
      aminoisoquinolines, pyrrolo[2,3-b]pyridines, and furo[2,3-d]pyrimidines, all of
      the type II class recognizing a DLG-out inactive conformation, were identified
      from screening of our in-house kinase focused sets. An exemplar from the furo[2,3
      d]pyrimidine series showed a dose proportional response in protection from
      hypothermia in a mouse model of TNFalpha induced lethal shock. 

PMID- 24900638
TI  - Toll-like receptor agonists for treatment of viral infections.

PMID- 24900639
TI  - Modulation of TRPV1 Receptor for Treatment of Pain and Other Disorders.

PMID- 24900640
TI  - Synthesis and antimalarial activity of 3,3-spiroanellated 5,6-disubstituted 1,2,4
      trioxanes.
AB  - Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34
      have been synthesized and appraised for their antimalarial activity against
      multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at
      doses ranging from 96 mg/kg * 4 days to 24 mg/kg * 4 days. The most active
      compound of the series (compound 25) provided 100% protection at 24 mg/kg * 4
      days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising
      activity. In this model, beta-arteether provided 100 and 20% protection at 48
      mg/kg * 4 days and 24 mg/kg * 4 days, respectively, by oral route. Compound 25
      displayed a similar in vitro pharmacokinetic profile to that of reference drug
      beta-arteether. The activity results demonstrated the importance of an aryl
      moiety at the C-5 position on the 1,2,4-trioxane pharmacophore. 

PMID- 24900641
TI  - Synthesis of 8-hydroxyquinoline derivatives as novel antitumor agents.
AB  - This letter describes the preparation of quinoline derivatives and their
      cytotoxic potentials toward human carcinoma cell lines. Among the selected
      compounds, 8-hydroxy-2-quinolinecarbaldehyde (3) showed the best in vitro
      cytotoxicity against the human cancer cell lines, including MDA231, T-47D,
      Hs578t, SaoS2, K562, SKHep1 (with a MTS50 range of 12.5-25 MUg/mL) and Hep3B
      (with a MTS50 range of 6.25+/-0.034 MUg/mL). The in vivo antitumor activity of
      compound 3 on subcutenaous Hep3B hepatocellular carcinoma xenograft in athymic
      nude mice was then studied. The results showed that the dose of 10 mg/kg/day of
      compound 3 with intraperitoneal injection for 9 days totally abolished the growth
      of the xenograft tumor of Hep3B with no histological damage on vital organs as
      compared with the control. The experimental results suggested that compound 3 has
      a good potential as an antitumor agent. 

PMID- 24900642
TI  - Metal impurities cause false positives in high-throughput screening campaigns.
AB  - Organic impurities in compound libraries are known to often cause false-positive
      signals in screening campaigns for new leads, but organic impurities do not fully
      account for all false-positive results. We discovered inorganic impurities in our
      screening library that can also cause positive signals for a variety of targets
      and/or readout systems, including biochemical and biosensor assays. We
      investigated in depth the example of zinc for a specific project and in
      retrospect in various HTS screens at Roche and propose a straightforward counter
      screen using the chelator TPEN to rule out inhibition caused by zinc. 

PMID- 24900643
TI  - Structure-Based Approach for the Discovery of Pyrrolo[3,2-d]pyrimidine-Based EGFR
      T790M/L858R Mutant Inhibitors.
AB  - The epidermal growth factor receptor (EGFR) family plays a critical role in vital
      cellular processes and in various cancers. Known EGFR inhibitors exhibit distinct
      antitumor responses against the various EGFR mutants associated with nonsmall
      cell lung cancer. The L858R mutation enhances clinical sensitivity to gefitinib
      and erlotinib as compared with wild type and reduces the relative sensitivity to
      lapatinib. In contrast, the T790M mutation confers drug resistance to gefitinib
      and erlotinib. We determined crystal structures of the wild-type and T790M/L858R
      double mutant EGFR kinases with reversible and irreversible pyrrolo[3,2
      d]pyrimidine inhibitors based on analogues of TAK-285 and neratinib. In these
      structures, M790 adopts distinct conformations to accommodate different
      inhibitors, whereas R858 allows conformational variations of the activation loop.
      These results provide structural insights for understanding the structure
      activity relationships that should contribute to the development of potent
      inhibitors against drug-sensitive or -resistant EGFR mutations. 

PMID- 24900644
TI  - Gadolinium Complex of (125)I/(127)I-RGD-DOTA Conjugate as a Tumor-Targeting
      SPECT/MR Bimodal Imaging Probe.
AB  - The work describes the synthesis and in vivo application of [Gd(L)(H2O)].xH2O,
      where L is a ((125)I/(127)I-RGD)- DOTA conjugate, as a tumor-targeting SPECT/MR
      bimodal imaging probe. Here, ((125)I/(127)I-RGD)-DOTA signifies a "cocktail
      mixture" of radioisotopic (1a, L = (125)I-RGD-DOTA) and natural (1b, L = (127)I
      RGD-DOTA) Gd complexes. The two complexes are chemically equivalent as revealed
      by HPLC, and their cocktail mixture exhibits the integrin-specific tumor
      enhancement, demonstrating that they constitute essentially a single bimodal
      imaging probe. Employment of a cocktail mixture thus proves to be a sole and
      practical approach to overcome the sensitivity difference problem between MRI and
      SPECT. 

PMID- 24900646
TI  - Synthesis and antimycobacterial activity of 2,1'-dihydropyridomycins.
AB  - Dihydropyridomycins 2 and 3, which lack the characteristic enol ester moiety of
      the potent antimycobacterial natural product pyridomycin (1), have been prepared
      from l-Thr, R- and S-hydroxy isovaleric acid, and 3-pyridinecarboxaldehyde. The
      2R isomer 2 shows only 4-fold lower anti-Mtb activity than 1, indicating that the
      enol ester moiety in the natural product is not critical for its biological
      activity. This finding establishes 2 as a potent and more practical lead for anti
      TB drug discovery. 

PMID- 24900645
TI  - A Fluorescent Styrylquinoline with Combined Therapeutic and Diagnostic Activities
      against Alzheimer's and Prion Diseases.
AB  - (E)-6-Methyl-4'-amino-2-styrylquinoline (3) is a small molecule with the proper
      features to potentially diagnose, deliver therapy and monitor response to therapy
      in protein misfolding diseases. These features include compound fluorescent
      emission in the NIR region and its ability to interact with both Abeta and prion
      fibrils, staining them with high selectivity. Styrylquinoline 3 also inhibits
      Abeta self-aggregation in vitro and prion replication in the submicromolar range
      in a cellular context. Furthermore, it is not toxic and is able to cross the
      blood brain barrier in vitro (PAMPA test). 

PMID- 24900648
TI  - Aldosterone synthase inhibitors: targeting chronic kidney disease and diabetic
      nephropathy.

PMID- 24900647
TI  - Bodilisant-a novel fluorescent, highly affine histamine h3 receptor ligand.
AB  - A piperidine-based lead structure for the human histamine H3 receptor (hH3R) was
      coupled with the BODIPY fluorophore and resulted in a strong green fluorescent
      (quantum yield, 0.92) hH3R ligand with affinity in the nanomolar concentration
      range (K i hH3R = 6.51 +/- 3.31 nM), named Bodilisant. Screening for affinities
      at histamine and dopamine receptor subtypes showed high hH3R preference.
      Bodilisant was used for visualization of hH3R in hH3R overexpressing HEK-293
      cells with fluorescence confocal laser scanning microscopy. In addition, in
      native human brain tissues, Bodilisant showed clear and displaceable images of
      labeled hH3R. 

PMID- 24900649
TI  - TRPV4 Antagonists: Potential Treatment for Congestive Heart Failure, Bladder
      Dysfunctions, and Pain.

PMID- 24900651
TI  - Irreversible inhibitors of cysteine proteases.

PMID- 24900650
TI  - PDE10 Inhibitors as Potential Treatment for Schizophrenia.

PMID- 24900652
TI  - The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2
      family protein-protein interactions.
AB  - Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is
      commonly associated with cancer cell survival and resistance to
      chemotherapeutics. Here, we describe the structure-based optimization of a series
      of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death.
      The role of the acidic nature of the sulfonamide moiety as it relates to potency,
      solubility, and clearance is examined. This has led to the discovery of novel
      heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263. 

PMID- 24900653
TI  - Azaindole-Based Inhibitors of Cdc7 Kinase: Impact of the Pre-DFG Residue, Val
      195.
AB  - To investigate the role played by the unique pre-DFG residue Val 195 of Cdc7
      kinase on the potency of azaindole-chloropyridines (1), a series of novel
      analogues with various chloro replacements were synthesized and evaluated for
      their inhibitory activity against Cdc7. X-ray cocrystallization using a surrogate
      protein, GSK3beta, and modeling studies confirmed the azaindole motif as the
      hinge binder. Weaker hydrophobic interactions with Met 134 and Val 195 by certain
      chloro replacements (e.g., H, methyl) led to reduced Cdc7 inhibition. Meanwhile,
      data from other replacements (e.g., F, O) indicated that loss of such hydrophobic
      interaction could be compensated by enhanced hydrogen bonding to Lys 90. Our
      findings not only provide an in-depth understanding of the pre-DFG residue as
      another viable position impacting kinase inhibition, they also expand the
      existing knowledge of ligand-Cdc7 binding. 

PMID- 24900654
TI  - Novel hybrid-type antimicrobial agents targeting the switch region of bacterial
      RNA polymerase.
AB  - The bacterial RNA polymerase (RNAP) is an ideal target for the development of
      antimicrobial agents against drug-resistant bacteria. Especially, the switch
      region within RNAP has been considered as an attractive binding site for drug
      discovery. Here, we designed and synthesized a series of novel hybrid-type
      inhibitors of bacterial RNAP. The antimicrobial activities were evaluated using a
      paper disk diffusion assay, and selected derivatives were tested to determine
      their MIC values. The hybrid-type antimicrobial agent 29 showed inhibitory
      activity against Escherichia coli RNAP. The molecular docking study suggested
      that the RNAP switch region would be the binding site of 29. 

PMID- 24900655
TI  - [3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective
      Phosphatidylinositol-3-kinase beta Inhibitors.
AB  - A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which
      were highly potent and selective inhibitors of PI3Kbeta. The template afforded
      the opportunity to develop novel SAR for both the hinge-binding (R3) and back
      pocket (R4) substitutents. While cellular potency was relatively modest due to
      high protein binding, the series displayed low clearance in rat, mouse, and
      monkey. 

PMID- 24900656
TI  - Discovery of novel N-substituted oxindoles as selective m1 and m4 muscarinic
      acetylcholine receptors partial agonists.
AB  - Activation of the M1 and M4 muscarinic acetylcholine receptors is thought to play
      an important role in improving the symptoms of schizophrenia. However, discovery
      of selective agonists for these receptors has been a challenge, considering the
      high sequence homology and conservation of the orthosteric acetylcholine binding
      site among muscarinic acetylcholine receptor subtypes. We report in this study
      the discovery of novel N-substituted oxindoles as potent muscarinic acetylcholine
      receptor partial agonists selective for M1 and M4 over M2, M3, and M5. Among
      these oxindoles, compound 1 showed high selectivity for the M1 and M4 receptors
      with remarkable penetration into the central nervous system. Compound 1 reversed
      methamphetamine- and apomorphine-induced psychosis-like behaviors with low
      potency to extrapyramidical and peripheral side effects. 

PMID- 24900657
TI  - Interrogation of the Active Sites of Protein Arginine Deiminases (PAD1, -2, and 
      4) Using Designer Probes.
AB  - Protein arginine deiminases (PADs) are involved in a number of cellular pathways,
      and they catalyze the transformation of peptidyl arginine residue into a
      citrulline as part of post-translational modifications. To understand ligand
      preferences, a group of probe molecules were investigated against PAD1, PAD2, and
      PAD4. These probe molecules carried a well-known covalent modifier of the
      catalytic cysteine residue, 2-chloroacetamidine moiety, which was tethered to an
      alpha-amino acid via a carbon linker. The chain length for the linker varied from
      0 to 4. Time-dependent assays indicated that 2-chloroacetamidine (2CA) with no
      linker inhibited all PAD enzymes with a similar trend in the second-order rate
      constants, although with poor affinity. Among the other three probe molecules,
      compound 3 with a three-carbon linker exhibited the best second-order rate
      constants for optimal ligand reactivity with the binding site. These analyses
      provide insights into the relative patterns of covalent inactivation of PAD
      isozymes and the design of novel inhibitors targeting PAD enzymes as potential
      therapeutic targets. 

PMID- 24900658
TI  - Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530
      for the treatment of solid tumors.
AB  - A new series of 7,8-disubstituted pyrazolobenzodiazepines based on the lead
      compound 1 have been synthesized and evaluated for their effects on mitosis and
      angiogenesis. Described herein is the design, synthesis, SAR, and antitumor
      activity of these compounds leading to the identification of R1530, which was
      selected for clinical evaluation. 

PMID- 24900659
TI  - Probing the binding site of abl tyrosine kinase using in situ click chemistry.
AB  - Modern combinatorial chemistry is used to discover compounds with desired
      function by an alternative strategy, in which the biological target is directly
      involved in the choice of ligands assembled from a pool of smaller fragments.
      Herein, we present the first experimental result where the use of in situ click
      chemistry has been successfully applied to probe the ligand-binding site of Abl
      and the ability of this enzyme to form its inhibitor. Docking studies show that
      Abl is able to allow the in situ click chemistry between specific azide and
      alkyne fragments by binding to Abl-active sites. This report allows medicinal
      chemists to use protein-directed in situ click chemistry for exploring the
      conformational space of a ligand-binding pocket and the ability of the protein to
      guide its inhibitor. This approach can be a novel, valuable tool to guide drug
      design synthesis in the field of tyrosine kinases. 

PMID- 24900660
TI  - Discovery of a novel broad-spectrum antifungal agent derived from albaconazole.
AB  - Synthesis of a strict structural analogue of albaconazole in which the
      quinazolinone ring is fused by a thiazole moiety led to the discovery of a new
      triazole with broad-spectrum antifungal activity. Compound I exhibited high in
      vitro activity against pathogenic Candida species and filamentous fungi and
      showed preliminary in vivo antifungal efficacy in a mice model of systemic
      candidiasis. 

PMID- 24900661
TI  - Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a
      Model of Pulmonary Edema.
AB  - High-throughput screening and subsequent hit optimization identified 1
      piperidinylbenzimidazoles, exemplified by compound 1, as TRPV4 inhibitors. Lead
      optimization identified potent TRPV4 blocker 19, which has good target activity
      and pharmacokinetic properties. Inhibitor 19 was then profiled in an in vivo rat
      model, demonstrating its ability to inhibit TRPV4-mediated pulmonary edema. 

PMID- 24900662
TI  - Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1
      Inhibitors.
AB  - The indenopyrazole framework was investigated as a new class of HIF-1alpha
      inhibitors. Indenopyrazole 2l was found to most strongly inhibit the hypoxia
      induced HIF-1alpha transcriptional activity (IC50 = 0.014 MUM) among all of the
      known compounds having relatively simple structures, unlike manassantins.
      Indenopyrazole 2l suppressed HIF-1alpha transcriptional activity without
      affecting both HIF-1alpha protein accumulation and HIF-1alpha/HIF-1beta
      heterodimerization in nuclei under the hypoxic conditions, suggesting that 2l
      probably affected the transcriptional pathway induced by the HIF-1alpha/HIF-1beta
      heterodimer. 

PMID- 24900663
TI  - Immune-Stimulatory Dinucleotide at the 5'-End of Oligodeoxynucleotides Is
      Critical for TLR9-Mediated Immune Responses.
AB  - Oligodeoxynucleotides (ODNs) containing a CpG or certain synthetic dinucleotides,
      referred to as immune-stimulatory dinucleotides, induce Toll-like receptor 9
      (TLR9)-mediated immune responses. Chemical modifications such as 2'-O
      methylribonucleotides incorporated adjacent to the immune-stimulatory
      dinucleotide on the 5'-side abrogate TLR9-mediated immune responses. In this
      study, we evaluated the effect of the location of immune-stimulatory
      dinucleotides in ODNs on TLR9-mediated immune responses. We designed and
      synthesized ODNs with two immune-stimulatory dinucleotides, one placed toward the
      5'-end region and the other toward the 3'-end region, incorporated 2'-O
      methylribonucleotides selectively preceding the 5'- or 3'-immune-stimulatory
      dinucleotide or both, and studied TLR9-mediated immune responses of these
      compounds in cell-based assays and in vivo in mice. These studies showed that an
      immune-stimulatory dinucleotide located closer to the 5'-end is critical for and
      dictates TLR9-mediated immune responses. These studies provide insights for the
      use of ODNs when employed as TLR9 agonists and antagonists or antisense agents. 

PMID- 24900664
TI  - High-Throughput Selectivity Assays for Small-Molecule Inhibitors of beta
      Catenin/T-Cell Factor Protein-Protein Interactions.
AB  - Two homogeneous high-throughput assays, AlphaScreen and fluorescence
      polarization, were established to quantify inhibitor selectivity between
      different protein-protein complexes. As a first case study, they have been
      successfully applied to the key protein-protein interactions in the downstream
      sites of the canonical Wnt signaling pathway. The aberrant formation of the beta
      catenin/T-cell factor (Tcf) complex is the major driving force for many cancers
      and fibroses. Crystallographic and biochemical studies reveal that the binding
      modes of Tcf, E-cadherin, and adenomatous polyposis coli (APC) to beta-catenin
      are identical and mutually exclusive. In the present study, two highly sensitive
      and robust assays were established to quantitatively evaluate inhibitor
      selectivity between beta-catenin/Tcf, beta-catenin/E-cadherin, and beta
      catenin/APC interactions. A pilot screen demonstrated the feasibility of the
      assays and yielded four hits for the disruption of beta-catenin/Tcf interactions.
      A potent and dual-selective beta-catenin/Tcf inhibitor was identified. 

PMID- 24900665
TI  - Drug discovery in an academic setting: playing to the strengths.
AB  - Drug discovery and medicinal chemistry initiatives in academia provide an
      opportunity to create a unique environment that is distinct from the traditional
      industrial model. Two characteristics of a university setting that are not
      usually associated with pharma are the ability to pursue high-risk projects and a
      depth of expertise, infrastructure, and capabilities in focused areas.
      Encouraging, supporting, and fostering drug discovery efforts that take advantage
      of these and other distinguishing characteristics of an academic setting can lead
      to novel and innovative therapies that might not be discovered otherwise. 

PMID- 24900666
TI  - Positive allosteric modulators of nicotinic acetylcholine receptor.

PMID- 24900667
TI  - Inhibition of mTOR Kinase and Cancer Treatment.

PMID- 24900668
TI  - The structure of anthracycline derivatives determines their subcellular
      localization and cytotoxic activity.
AB  - The cytotoxic activities and subcellular localizations of clinically used and
      synthetic analogues of the anthracycline family of chemotherapeutic agents were
      studied. The structures of the anthracycline derivatives affected their
      cytotoxicity and the time required for these compounds to exert cytotoxic effects
      on tumor cells. Fluorescent DNA intercalator displacement experiments
      demonstrated that there was no correlation between the DNA intercalation
      properties and the cytotoxicity of the studied anthracycline derivatives.
      Confocal microscopy experiments indicated that structural differences led to
      differences in subcellular localization. All studied anthracycline derivatives
      were observed in lysosomes, suggesting that this organelle, which is involved in
      several processes leading to malignancy, may contain previously unidentified
      molecular targets for these antitumor agents. 

PMID- 24900669
TI  - Promising in Vitro anti-Alzheimer Properties for a Ruthenium(III) Complex.
AB  - Metal complexes represent today an attractive class of experimental anti
      Alzheimer agents with the potential of blocking beta-amyloid 1-42 aggregation and
      scavenging its toxicity. Three representative ruthenium(III) complexes, namely
      NAMI A, KP1019, and PMRU20, were specifically evaluated to this end in an
      established in vitro model of AD relying on primary cortical neurons. Notably,
      PMRU20 turned out to be highly effective in protecting cortical neurons against
      Abeta 1-42 toxicity, while the other tested ruthenium compounds were poorly
      active or even inactive; we also found that PMRU20 is virtually devoid of any
      significant toxicity in vitro at the applied concentrations. Interestingly,
      PMRU20 was neuroprotective even against the toxicity induced by Abeta 25-35. The
      direct reaction of PMRU20 with Abeta 1-42 was explored through ESI MS analysis
      and some adduct formation evidenced. In addition, thioflavin T assays revealed
      that PMRU20 greatly reduces Abeta 1-42 aggregation. The implications of these
      findings are discussed in relation to emerging treatment strategies for the
      Alzheimer's disease. 

PMID- 24900670
TI  - Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.
AB  - A novel series of alkoxyimino derivatives as S1P1 agonists were discovered
      through de novo design using FTY720 as the chemical starting point. Extensive
      structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4
      cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3
      carboxylic acid (32, BAF312, Siponimod), which has recently completed phase 2
      clinical trials in patients with relapsing-remitting multiple sclerosis. 

PMID- 24900671
TI  - Deuterated clopidogrel analogues as a new generation of antiplatelet agents.
AB  - Clopidogrel (CPG) is an antithrombotic prodrug that needs hepatic cytochrome P450
      (CYP) enzymes for its bioactivation. The clinical effects of CPG have been
      associated with high intersubject variability and a certain level of resistance.
      Recently, comprehensive biotransformation studies of CPG support that the
      observed clinical uncertainty stems from the low bioactivation efficiency, which
      is attributed to extensive attritional metabolism (e.g., hydrolysis of the methyl
      ester functionality and oxidation of the piperidine moiety). With the goal of
      potentiating the desired thiophene 2-oxidation through minimal structural
      modification, we have adopted the strategy of targeted metabolism shift and have
      designed and synthesized deuterated piperidine analogues of CPG. In vitro studies
      showed that the prodrug activation percentages have been significantly increased
      for the deuterated analogues as a result of stability enhancement of the
      piperidine moiety. In a pharmacological study with a rat model, oral
      administration of the deuterated analogues also demonstrated higher inhibitory
      activity than that of CPG against adenosine diphosphate (ADP) induced platelet
      aggregation. These deuterated analogues represent a new generation of
      antiplatelet agents with the potential to overcome the major clinical drawbacks
      of CPG. 

PMID- 24900672
TI  - Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists
      of WDR5-MLL Interaction.
AB  - The WD40-repeat protein WDR5 plays a critical role in maintaining the integrity
      of MLL complexes and fully activating their methyltransferase function. MLL
      complexes, the trithorax-like family of SET1 methyltransferases, catalyze
      trimethylation of lysine 4 on histone 3, and they have been widely implicated in
      various cancers. Antagonism of WDR5 and MLL subunit interaction by small
      molecules has recently been presented as a practical way to inhibit activity of
      the MLL1 complex, and N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl)
      benzamides were reported as potent and selective antagonists of such an
      interaction. Here, we describe the protein crystal structure guided optimization
      of prototypic compound 2 (K dis = 7 MUM), leading to identification of more
      potent antagonist 47 (K dis = 0.3 MUM). 

PMID- 24900673
TI  - Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor
      Activity against B-Raf-Driven Tumors.
AB  - Hyperactive signaling of the MAP kinase pathway resulting from the constitutively
      active B-Raf(V600E) mutated enzyme has been observed in a number of human tumors,
      including melanomas. Herein we report the discovery and biological evaluation of
      GSK2118436, a selective inhibitor of Raf kinases with potent in vitro activity in
      oncogenic B-Raf-driven melanoma and colorectal carcinoma cells and robust in vivo
      antitumor and pharmacodynamic activity in mouse models of B-Raf(V600E) human
      melanoma. GSK2118436 was identified as a development candidate, and early
      clinical results have shown significant activity in patients with B-Raf mutant
      melanoma. 

PMID- 24900675
TI  - Regenerative medicinal chemistry: the in situ control of stem cells.
AB  - In recent years, there has been mounting evidence to support the presence of stem
      and progenitor cells within many adult tissues that retain the capacity to
      proliferate and differentiate, thereby contributing to tissue homeostasis and
      repair. In line with these discoveries, there have been increasing efforts to
      develop new agents that target these resident stem and progenitor cell
      populations in situ to augment or to stimulate repair and regeneration processes.
      Two such agents are approved drugs, and several more are currently in clinical
      and preclinical development. Through this emerging therapeutic paradigm there is
      enormous scope for medicinal chemistry to play a pivotal role in regenerative
      medicine. The potential impact of regenerative medicinal chemistry is profound,
      and future studies will reveal which tissue types or disease states will prove
      most readily tractable through this approach. 

PMID- 24900676
TI  - Tough times for medicinal chemists: are we to blame?
AB  - In the United States, medicinal chemists continue to face job insecurity and high
      rates of unemployment. The situation is unlikely to improve in the near future.
      Is there a light at the end of the tunnel? Is there anything we can do to
      revitalize our community? The answer may be right in front of us. 

PMID- 24900677
TI  - Targeting CCR2 Receptor To Treat Inflammation Diseases and Disorders.

PMID- 24900678
TI  - Inhibition of notch pathway signaling: a one compound mission to treat cancer.

PMID- 24900679
TI  - Aldosterone synthase inhibitors.

PMID- 24900680
TI  - Selective Cyp11B1 Inhibitors for the Treatment of Cortisol Dependent Diseases.

PMID- 24900681
TI  - Cyclopropyl-Fused 1,3-Thiazepines as BACE1 and BACE2 Inhibitors.

PMID- 24900682
TI  - Orally active fumagillin analogues: transformations of a reactive warhead in the
      gastric environment.
AB  - Semisynthetic analogues of fumagillin, 1, inhibit methionine aminopeptidase-2
      (MetAP2) and have entered the clinic for the treatment of cancer. An optimized
      fumagillin analogue, 3 (PPI-2458), was found to be orally active, despite
      containing a spiroepoxide function that formed a covalent linkage to the target
      protein. In aqueous acid, 3 underwent ring-opening addition of water and HCl,
      leading to four products, 4-7, which were characterized in detail. The
      chlorohydrin, but not the diol, products inhibited MetAP2 under weakly basic
      conditions, suggesting reversion to epoxide as a step in the mechanism. In
      agreement, chlorohydrin 6 was shown to revert rapidly to 3 in rat plasma. In an
      ex vivo assay, rats treated with purified acid degradants demonstrated inhibition
      of MetAP2 that correlated with the biochemical activity of the compounds. Taken
      together, the results indicate that degradation of the parent compound was
      compensated by the formation of active equivalents leading to a pharmacologically
      useful level of MetAP2 inhibition. 

PMID- 24900683
TI  - Benzanilide-Biphenyl Replacement: A Bioisosteric Approach to Quinoline
      Carboxamide-Type ABCG2 Modulators.
AB  - Recently reported compounds such as UR-COP78 (6) are among the most potent and
      selective ABCG2 modulators known so far but are prone to rapid enzymatic cleavage
      at the central benzanilide moiety. In search for more stable analogues, according
      to a bioisosteric approach, a series of N-(biphenyl-3-yl)quinoline carboxamides
      was prepared by solid phase and solution phase synthesis. The biphenyl moiety was
      constructed by Suzuki coupling. Inhibition of ABCB1 and ABCG2 was determined in a
      calcein-AM and a Hoechst 33342 microplate assay, respectively. Most synthesized
      compounds selectively inhibited the ABCG2 transporter at submicromolar
      concentrations with a maximal inhibitory effect (I max) over 90% (e.g., UR-COP228
      (22a), IC50 591 nM, I max 109%; UR-COP258 (31), IC50 544 nM, I max 112%), though
      with lower potency and selectivity than 6. The biphenyl analogues are
      considerably more stable and demonstrate that the benzanilide core is not a
      crucial structural feature of quinoline carboxamide-type ABCG2 modulators. 

PMID- 24900684
TI  - Design, Synthesis, and Pharmacological Evaluation of Fluorescent and Biotinylated
      Antagonists of rho1 GABAC Receptors.
AB  - The rho1 GABAC receptor is a ligand-gated chloride ion channel that shows promise
      as a therapeutic target for myopia, sleep disorders, memory and learning
      facilitation, and anxiety-related disorders. As such, there is a need for
      molecular probes to understand the role GABAC receptors play in physiological and
      pathological processes. To date, no labeled (either radioactive or fluorescent)
      GABAC selective ligand has been developed that can act as a marker for GABAC
      receptor visualization and localization studies. Herein, we report a series of
      fluorescent ligands containing different-sized linkers and fluorophores based
      around (S)-4-ACPBPA [(4-aminocyclopenten-1-yl)-butylphosphinic acid], a selective
      GABAC antagonist. One of these conjugates, (S)-4-ACPBPA-C5-BODIPY (13), displayed
      moderate potency (IC50 = 58.61 MUM) and selectivity (>100 times) for rho1 over
      alpha1beta2gamma2L GABAA receptors. These conjugates are novel lead agents for
      the development of more potent and selective fluorescent probes for studying the
      localization and function of GABAC receptors in living cells. 

PMID- 24900685
TI  - Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the
      Extracellular Signaling Pathway.
AB  - The aberrant function of c-Met kinase signaling pathway is ubiquitously involved
      in a broad spectrum of human cancers; thus, a strong rationale exists for
      targeting the kinase pathway in cancer therapy. Via integration of computational
      and experimental studies, anthraquinone derivatives were identified for the first
      time as potent c-Met kinase inhibitors in this research. The aberrant activation
      of the c-Met kinase pathway results from (TPR)-Met, MET gene mutation, or
      amplification and a hepatocyte growth factor (HGF)/scatter factor-dependent
      autocrine or paracrine mechanism. However, anthraquinone derivatives exclusively
      suppressed c-Met phosphorylation stimulated by HGF in A549 cells, indicating that
      the compounds possess the ability to block the extracellular HGF-dependent
      pathway. A surface plasmon resonance assay revealed that the most potent
      compound, 2a, shows a high binding affinity for HGF with an equilibrium
      dissociation constant of 1.95 MUM. The dual roles of compound 2a demonstrate the
      potency of anthraquinone derivatives and provide a new design solution for the c
      Met kinase signaling pathway. 

PMID- 24900686
TI  - Identification of RO4597014, a Glucokinase Activator Studied in the Clinic for
      the Treatment of Type 2 Diabetes.
AB  - To resolve the metabolite redox cycling associated with our earlier clinical
      compound 2, we carried out lead optimization of lead molecule 1. Compound 4
      showed improved lipophilic ligand efficiency and demonstrated robust glucose
      lowering in diet-induced obese mice without a liability in predictive preclinical
      drug safety studies. Thus, it was selected as a clinical candidate and further
      studied in type 2 diabetic patients. Clinical data suggests no evidence of
      metabolite cycling, which is consistent with the preclinical profiling of
      metabolism. 

PMID- 24900688
TI  - Combination Therapy: JAK PI3K/mTOR. A Novel Approach for Cancer Treatment.

PMID- 24900687
TI  - Synthesis and Pharmacological Characterization of Two Novel, Brain Penetrating
      P2X7 Antagonists.
AB  - The synthesis and preclinical characterization of two novel, brain penetrating
      P2X7 compounds will be described. Both compounds are shown to be high potency
      P2X7 antagonists in human, rat, and mouse cell lines and both were shown to have
      high brain concentrations and robust receptor occupancy in rat. Compound 7 is of
      particular interest as a probe compound for the preclinical assessment of P2X7
      blockade in animal models of neuro-inflammation. 

PMID- 24900690
TI  - Dihydrooxazines As Inhibitors of BACE-1 or BACE-2.

PMID- 24900689
TI  - PAK1: A Therapeutic Target for Cancer Treatment.

PMID- 24900691
TI  - Novel thiazolobenzodiazepines as inhibitors of histamine h3 receptor.

PMID- 24900692
TI  - PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the
      Visualization of beta-Amyloid Plaques.
AB  - In an effort toward the visualization of beta-amyloid plaques by in vivo imaging
      techniques, we have conjugated an optimized derivative of the Pittsburgh compound
      B (PiB), a well-established marker of Abeta plaques, to DO3A-monoamide that is
      capable of forming stable, noncharged complexes with different trivalent metal
      ions including Gd(3+) for MRI and (111)In(3+) for SPECT applications. Proton
      relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide
      Abeta1-40 and to human serum albumin, resulting in a two- and four-fold
      relaxivity increase, respectively. Ex vivo immunohistochemical studies showed
      that the DO3A-PiB complexes selectively target Abeta plaques on Alzheimer's
      disease human brain tissue. Ex vivo biodistribution data obtained for the (111)In
      analogue pointed to a moderate blood-brain barrier (BBB) penetration in adult
      male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min
      postinjection. 

PMID- 24900693
TI  - Discovery of tetrahydropyrazolopyrimidine carboxamide derivatives as potent and
      orally active antitubercular agents.
AB  - Tetrahydropyrazolo[1,5-a]pyrimidine scaffold was identified as a hit series from
      a Mycobacterium tuberculosis (Mtb) whole cell high through-put screening (HTS)
      campaign. A series of derivatives of this class were synthesized to evaluate
      their structure-activity relationship (SAR) and structure-property relationship
      (SPR). Compound 9 had a promising in vivo DMPK profile in mouse and exhibited
      potent in vivo activity in a mouse efficacy model, achieving a reduction of 3.5
      log CFU of Mtb after oral administration to infected mice once a day at 100 mg/kg
      for 28 days. Thus, compound 9 is a potential candidate for inclusion in
      combination therapies for both drug-sensitive and drug-resistant TB. 

PMID- 24900694
TI  - Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.
AB  - The p53 tumor suppressor is a potent transcription factor that plays a key role
      in the regulation of cellular responses to stress. It is controlled by its
      negative regulator MDM2, which binds directly to p53 and inhibits its
      transcriptional activity. MDM2 also targets p53 for degradation by the
      proteasome. Many tumors produce high levels of MDM2, thereby impairing p53
      function. Restoration of p53 activity by inhibiting the p53-MDM2 interaction may
      represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical
      small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2.
      In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the
      p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or
      regression of human tumor xenografts. 

PMID- 24900695
TI  - Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP
      Activated Protein Kinase Activators.
AB  - Adenosine 5'-monophosphate-activated protein kinase (AMPK) is emerging as a
      promising drug target for its regulatory function in both glucose and lipid
      metabolism. Compound PT1 (5) was originally identified from high throughput
      screening as a small molecule activator of AMPK through the antagonization of the
      autoinhibition in alpha subunits. In order to enhance its potency at AMPK and
      bioavailability, structure-activity relationship studies have been performed and
      resulted in a novel series of AMPK activators based on an alkene oxindole
      scaffold. Following their evaluation in pharmacological AMPK activation assays,
      lead compound 24 was identified to possess improved potency as well as favorable
      pharmacokinetic profile. In the diet-induced obesity (DIO) mouse model, compound
      24 was found to improve glucose tolerance and alleviate insulin resistance. The
      in vitro and in vivo data for these alkene oxindoles warrant further studies for
      their potential therapeutic medications in metabolic associated diseases. 

PMID- 24900697
TI  - Imidazopyrazine Derivatives As Inhibitors of mTOR.

PMID- 24900696
TI  - Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4
      Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold.
AB  - Fibroblast activation protein (FAP) is a serine protease that is generally
      accepted to play an important role in tumor growth and other diseases involving
      tissue remodeling. Currently there are no FAP inhibitors with reported
      selectivity toward both the closely related dipeptidyl peptidases (DPPs) and
      prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP
      inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have
      explored the effects of substituting the quinoline ring and varying the position
      of its sp(2) hybridized nitrogen atom. The most promising inhibitors combined low
      nanomolar FAP inhibition and high selectivity indices (>10(3)) with respect to
      both the DPPs and PREP. Preliminary experiments on a representative inhibitor
      demonstrate that plasma stability, kinetic solubility, and log D of this class of
      compounds can be expected to be satisfactory. 

PMID- 24900699
TI  - Tricyclic Pyrimidines As Inhibitors of DYRK1A/DYRK1B As Potential Treatment for
      Down's Syndrome or Alzheimer's Disease.

PMID- 24900698
TI  - Negative allosteric modulators of metabotropic glutamate receptor subtype.

PMID- 24900700
TI  - Identification of New Nonsteroidal RORalpha Ligands; Related Structure-Activity
      Relationships and Docking Studies.
AB  - A high throughput screen was developed to identify novel, nonsteroidal RORalpha
      agonists. Among the validated hit compounds, the 4-(4-(benzyloxy)phenyl)-5
      carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent.
      Among the numerous analogues tested, compounds 8 and 9 showed the highest
      activity. Key structure-activity relationships (SAR) were established, where
      benzyl and urea moieties were both identified as very important elements to
      maintain the activity. Most notably, the SAR were consistent with the binding
      mode of the compound 8 (S-isomer) in the RORalpha docking model that was
      developed in this program. As predicted by the model, the urea moiety is engaged
      in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382.
      The benzyl group is located in a wide hydrophobic pocket. The structural
      relationships reported in this letter will help in further optimization of this
      compound series and will provide novel synthetic probes helpful for elucidation
      of complex RORalpha physiopathology. 

PMID- 24900702
TI  - Metabolically Stable tert-Butyl Replacement.
AB  - Susceptibility to metabolism is a common issue with the tert-butyl group on
      compounds of medicinal interest. We demonstrate an approach of removing all the
      fully sp(3) C-Hs from a tert-butyl group: replacing some C-Hs with C-Fs and
      increasing the s-character of the remaining C-Hs. This approach gave a
      trifluoromethylcyclopropyl group, which increased metabolic stability.
      Trifluoromethylcyclopropyl-containing analogues had consistently higher metabolic
      stability in vitro and in vivo compared to their tert-butyl-containing
      counterparts. 

PMID- 24900701
TI  - Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase.
AB  - We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron
      emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal
      chemistry efforts directed toward reducing lipophilicity led to the synthesis of
      a series of imidazole analogues. Compound 6 was chosen for further profiling due
      to its appropriate physical chemical properties and excellent FAAH inhibition
      potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH
      specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH
      in the brain. 

PMID- 24900703
TI  - Enzymatic stability and immunoregulatory efficacy of a synthetic indolicidin
      analogue with regular enantiomeric sequence.
AB  - Cell-mediated immunity plays a major role in protecting the host from viral
      infections and tumor challenge. Here, we report the enzymatic stability and
      adjuvanticity of a peptiomimetic stereoisomer of the bovine neutrophil peptide
      indolicidin. The analogue, dubbed ld-indolicidin, contains the regular
      enantiomeric sequence of indolicidin and is synthesized by general stepwise solid
      phase strategy. ld-Indolicidin possesses high resistance to enzymatic degradation
      and shows tolerance in mice. As vaccine adjuvant, ld-indolicidin is better able
      than the native form of indolicidin to enhance cell-mediated immune responses,
      using inactivated H5N1 virus as a model antigen. Taken together, these results
      open up a new approach to the development of vaccine adjuvants and immunotherapy
      technologies. 

PMID- 24900704
TI  - Development of Unsymmetrical Dyads As Potent Noncarbohydrate-Based Inhibitors
      against Human beta-N-Acetyl-d-hexosaminidase.
AB  - Human beta-N-acetyl-d-hexosaminidase has gained much attention due to its roles
      in several pathological processes and been considered as potential targets for
      disease therapy. A novel and efficient skeleton, which was an unsymmetrical dyad
      containing naphthalimide and methoxyphenyl moieties with an alkylamine spacer
      linkage as a noncarbohydrate-based inhibitor, was synthesized, and the activities
      were valuated against human beta-N-acetyl-d-hexosaminidase. The most potent
      inhibitor exhibits high inhibitory activity with K i values of 0.63 MUM. The
      straightforward synthetic manners of these unsymmetrical dyads and understanding
      of the binding model could be advantageous for further structure optimization and
      development of new therapeutic agents for Hex-related diseases. 

PMID- 24900705
TI  - Identification of Selective Nanomolar Inhibitors of the Human Neuraminidase,
      NEU4.
AB  - The human neuraminidase enzymes (hNEU) play important roles in human physiology
      and pathology. The lack of potent and selective inhibitors toward these enzymes
      has limited our understanding of their function and the development of
      therapeutic applications. Here we report the evaluation of a panel of compounds
      against the four human neuraminidase isoenzymes. Among the compounds tested, we
      identified the first selective, nanomolar inhibitors of the human neuraminidase 4
      enzyme (NEU4). The most potent NEU4 inhibitor (5-acetamido-9-[4
      hydroxymethyl[1,2,3]triazol-1-yl]-2,3,5,9-tetradeoxy-d-glycero-d-galacto-2
      nonulopyranosonic acid) was found to have an inhibitory constant (K i ) of 30 +/-
      19 nM and was 500-fold selective for its target over the other hNEU isoenzymes
      tested in vitro (NEU1, NEU2, and NEU3). This is the first report of any inhibitor
      of hNEU with nanomolar potency, and this confirms that the 2,3-didehydro-2-deoxy
      N-acetylneuraminic acid (DANA) scaffold can be exploited to develop new, potent,
      and selective inhibitors that target this important family of human enzymes. 

PMID- 24900706
TI  - New Promising Compounds with in Vitro Nanomolar Activity against Trypanosoma
      cruzi.
AB  - The antiparasitic activity of azole and new 4-aminopyridine derivatives has been
      investigated. The imidazoles 1 and 3-5 showed a potent in vitro antichagasic
      activity with IC50 values in the low nanomolar concentration range. The (S)-1,
      (S)-3, and (S)-5 enantiomers showed (up to) a thousand-fold higher activity than
      the reference drug benznidazole and furthermore low cytotoxicity on rat myogenic
      L6 cells. 

PMID- 24900707
TI  - Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic
      Spirocycles.
AB  - GPR40 (FFAR1 or FFA1) is a target of high interest being pursued to treat type II
      diabetes due to its unique mechanism leading to little risk of hypoglycemia. We
      recently reported the discovery of AM-1638 (2), a potent full agonist of GPR40.
      In this report, we present the discovery of GPR40 full agonists containing
      conformationally constrained tricyclic spirocycles and their structure-activity
      relationships leading to more potent agonists such as AM-5262 (26) with improved
      rat PK profile and general selectivity profile. AM-5262 enhanced glucose
      stimulated insulin secretion (mouse and human islets) and improved glucose
      homeostasis in vivo (OGTT in HF/STZ mice) when compared to AM-1638. 

PMID- 24900708
TI  - New Peptide-based antimicrobials for tackling drug resistance in bacteria: single
      cell fluorescence imaging.
AB  - New peptide molecules with metal binding abilities proved to be active against
      multidrug resistant clinical isolates. One of them labeled with a dansylated
      lysine has been imaged inside single-multidrug resistant bacteria cells by deep
      ultraviolet fluorescence, showing a heterogeneous subcellular localization. The
      fluorescence intensity is clearly related to the accumulation of the drug inside
      the bacteria, being dependent both on its concentration and on the incubation
      time with cells. 

PMID- 24900711
TI  - Mayo v. Prometheus: A Year Later.
AB  - Last year's U.S. Supreme Court decision in Mayo v. Prometheus regarding the
      patent eligibility of diagnostic method claims will probably have the most
      profound lasting effect of any recent court decision on the biopharmaceutical
      industry. The Mayo decision changed the evaluation of patent eligibility of a
      method claim under 35 U.S.C. S 101. The new evaluation is a more difficult
      standard to clear and needs to be considered prior to filing a patent
      application. 

PMID- 24900709
TI  - Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor.
AB  - The objective of the described research effort was to identify a novel serotonin
      and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine
      transporter activity and acceptable metabolic stability and exhibiting minimal
      drug-drug interaction. We describe herein the discovery of a series of 3
      substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective
      SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory
      activity in the formalin model of pain behavior. Compound 1 thus represents a
      potential new probe to explore utility of SNRIs in central nervous system
      disorders, including chronic pain conditions. 

PMID- 24900712
TI  - FPRL-1 Receptor Modulators May Provide Treatment for Inflammation.

PMID- 24900710
TI  - Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization
      of the Arylsulfonamide Scaffold.
AB  - A new class of potent matrix metalloproteinase (MMP) inhibitors designed by
      structure-based optimization of the well-known arylsulfonamide scaffold is
      presented. Molecules show an ethylene linker connecting the sulfonamide group
      with the P1' aromatic portion and a d-proline residue bearing the zinc-binding
      group. The affinity improvement provided by these modifications led us to
      discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding
      group, which might be a promising lead molecule. Notably, a significant
      selectivity for MMP-8, MMP-12, and MMP-13 was observed with respect to MMP-1 and
      MMP-7. 

PMID- 24900713
TI  - ERK2 Inhibitors May Provide Treatment for Cancer.

PMID- 24900714
TI  - beta-Secretase Inhibitors for the Treatment of Alzheimer's Disease and Down's
      Syndrome.

PMID- 24900715
TI  - Identification of a series of compounds with potent antiviral activity for the
      treatment of enterovirus infections.
AB  - Rhinovirus (genus enterovirus) infections are responsible for many of the severe
      exacerbations of asthma and chronic obstructive pulmonary disease. Other members
      of the genus can cause life-threatening acute neurological infections. There is
      currently no antiviral drug approved for the treatment of such infections. We
      have identified a series of potent, broad-spectrum antiviral compounds that
      inhibit the replication of the human rhinovirus, Coxsackie virus, poliovirus, and
      enterovirus-71. The mechanism of action of the compounds has been established as
      inhibition of a lipid kinase, PI4KIIIbeta. Inhibition of hepatitis C replication
      in a replicon assay correlated with enterovirus inhibition. 

PMID- 24900716
TI  - Identification of vitamin d3-based hedgehog pathway inhibitors that incorporate
      an aromatic a-ring isostere.
AB  - Previous structure-activity relationship studies for vitamin D3 (VD3) inhibition
      of Hedgehog (Hh) signaling directed the design, synthesis, and evaluation of a
      series of VD3-based analogues that contain an aromatic A-ring mimic.
      Characterization of these compounds in a series of cellular assays demonstrated
      their ability to potently and selectively down-regulate Hh pathway signaling. The
      most active of these, 17, inhibited pathway signaling in Hh-dependent mouse
      fibroblasts (IC50 = 0.74 +/- 0.1 MUM) and cultured cancer cells (IC50 values 3.8
      +/- 0.1 to 5.2 +/- 0.2 MUM). In addition, 17 demonstrated reduced activation of
      the vitamin D receptor (VDR) compared to VD3 in these cellular models. These
      results suggest that VD3-based analogues with an aromatic A-ring are a valid
      scaffold for the development of more selective and potent Hh pathway inhibitors
      and identify 17 as an intriguing lead from this class of compounds for further
      development. In addition, our analysis of Hh pathway inhibitors in cancer cells
      suggests that the murine basal cell carcinoma cell line ASZ001 and the human
      medulloblastoma cell line DAOY are appropriate in vitro cancer models for early
      stage evaluation of pathway inhibition. 

PMID- 24900717
TI  - Structure-Activity Relationships and in Vivo Evaluation of Quinoxaline
      Derivatives for PET Imaging of beta-Amyloid Plaques.
AB  - This letter describes the synthesis, structure-activity relationships, and in
      vivo evaluation of a new series of 2-phenylquinoxaline (PQ) derivatives for
      imaging beta-amyloid (Abeta) plaques in Alzheimer's disease (AD). In experiments
      in vitro, the affinity of the derivatives for Abeta aggregates varied, with K i
      values of 0.895 to 1180 nM. In brain sections from AD patients, derivatives with
      a K i of less than 111 nM intensely labeled Abeta plaques, while those with
      values over 242 nM showed no marked labeling. In biodistribution experiments
      using normal mice, the derivatives showed good uptake into (4.69-7.59 %ID/g at 2
      or 10 min postinjection) and subsequent washout from (1.48-3.08 %ID/g at 60 min
      postinjection) the brain. In addition, [(18)F]PQ-6 labeled Abeta plaques in vivo
      in APP transgenic mice, while it showed nonspecific binding in the white matter.
      Further structural optimization based on [(18)F]PQ-6 may lead to more useful PET
      probes for imaging Abeta plaques. 

PMID- 24900718
TI  - 4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1
      Integrase Inhibitors.
AB  - A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N
      hydroxyimide chelating functionality was evaluated for their inhibitory
      properties against human immunodeficiency virus type 1 integrase (HIV-1 IN).
      Several derivatives displayed low nanomolar IC50 values comparable to that of the
      clinically used raltegravir. A marked effect of one compound on both primary IN
      catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a
      novel IN inhibition mechanism establishing it as a potential new generation IN
      inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at
      position 4 by carboxamido chains was beneficial for antiviral activity since
      reproducible low micromolar anti-HIV activities were obtained for the first time
      within this scaffold. 

PMID- 24900719
TI  - C-Glucopyranosyl-1,2,4-triazoles As New Potent Inhibitors of Glycogen
      Phosphorylase.
AB  - Glycogen phosphorylase inhibitors are considered as potential antidiabetic
      agents. 3-(beta-d-Glucopyranosyl)-5-substituted-1,2,4-triazoles were prepared by
      acylation of O-perbenzoylated N (1)-tosyl-C-beta-d-glucopyranosyl formamidrazone
      and subsequent removal of the protecting groups. The best inhibitor was 3-(beta-d
      glucopyranosyl)-5-(2-naphthyl)-1,2,4-triazole (K i = 0.41 MUM against rabbit
      muscle glycogen phosphorylase b). 

PMID- 24900720
TI  - Pyrazolo[3,4-d]pyrimidine Prodrugs: Strategic Optimization of the Aqueous
      Solubility of Dual Src/Abl Inhibitors.
AB  - Design and synthesis of prodrugs of promising drug candidates represents a valid
      strategy to overcome the lack of favorable ADME properties, in particular aqueous
      solubility and bioavailability. We report herein the successful application of
      this strategy with two representative pyrazolo[3,4-d]pyrimidine derivatives (1
      and 2), which led to the development of the corresponding and highly water
      soluble antitumor prodrugs (7 and 8). In vitro studies confirmed a significant
      improvement of aqueous solubility and, for compound 8, good plasma stability,
      suggesting superior in vivo bioavailability. As expected, the uncleaved water
      soluble prodrugs 7 and 8 showed no activity toward the enzymatic targets (c-Src
      and c-Abl) but revealed promising antiproliferative activity in myeloid cell
      lines, as a consequence of the in vitro hydrolysis of the selected solubilizing
      moiety, followed by the release of the active compounds (1 and 2). 

PMID- 24900721
TI  - Discovery of novel insulin-like growth factor-1 receptor inhibitors with unique
      time-dependent binding kinetics.
AB  - This letter describes a series of small molecule inhibitors of IGF-1R with unique
      time-dependent binding kinetics and slow off-rates. Structure-activity and
      structure-kinetic relationships were elucidated and guided further optimizations
      within the series, culminating in compound 2. With an IGF-1R dissociative half
      life (t 1/2) of >100 h, compound 2 demonstrated significant and extended PD
      effects in conjunction with tumor growth inhibition in xenograft models at a
      remarkably low and intermittent dose, which correlated with the observed in vitro
      slow off-rate properties. 

PMID- 24900722
TI  - Discovery of Pyridones As Oral AMPK Direct Activators.
AB  - AMP-activated protein kinase (AMPK) is an evolutionarily conserved fuel-sensing
      enzyme that is activated in shortage of energy and suppressed in its surfeit.
      AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity,
      alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory
      changes. Thus, AMPK is a well-received therapeutic target for type 2 diabetes and
      other metabolic disorders. Here, we will report the discovery of pyrrolopyridone
      derivatives as AMPK direct activators. We will illustrate the synthesis and
      structure-activity relationships of the series as well as some pharmacokinetic
      results. Some compounds exhibited encouraging oral exposure and were evaluated in
      a mouse diabetic model. Compound 17 showed oral activity at 30 mg/kg on blood
      glucose. 

PMID- 24900723
TI  - Design, Synthesis, and Antiplasmodial Activity of Hybrid Compounds Based on
      (2R,3S)-N-Benzoyl-3-phenylisoserine.
AB  - A series of hybrid compounds based on (2R,3S)-N-benzoyl-3-phenylisoserine,
      artemisinin, and quinoline moieties was synthesized and tested for in vitro
      antiplasmodial activity against erythrocytic stages of K1 and W2 strains of
      Plasmodium falciparum. Two hybrid compounds incorporating (2R,3S)-N-benzoyl-3
      phenylisoserine and artemisinin scaffolds were 3- to 4-fold more active than
      dihydroartemisinin, with nanomolar IC50 values against Plasmodium falciparum K1
      strain. 

PMID- 24900724
TI  - Synthesis, Antiplasmodial Activity, and beta-Hematin Inhibition of
      Hydroxypyridone-Chloroquine Hybrids.
AB  - A series of noncytotoxic 4-aminoquinoline-3-hydroxypyridin-4-one hybrids were
      synthesized on the basis of a synergistic in vitro combination of a precursor N
      alkyl-3-hydroxypyridin-4-one with chloroquine (CQ) and tested in vitro against CQ
      resistant (K1 and W2) and sensitive (3D7) strains of Plasmodium falciparum. In
      vitro antiplasmodial activity of the precursors was negated by blocking the
      chelator moiety via complexation with gallium(III) or benzyl protection. None of
      the precursors inhibited beta-hematin formation. Most hybrids were more potent
      inhibitors of beta-hematin formation than CQ, and a correlation between
      antiplasmodial activity and inhibition of beta-hematin formation was observed.
      Potent hybrids against K1, 3D7, and W2, respectively, were 8c (0.13, 0.004, and
      0.1 MUM); 8d (0.08, 0.01, and 0.02 MUM); and 7g (0.07, 0.03, and 0.08 MUM). 

PMID- 24900725
TI  - Semisynthesis, cytotoxic activity, and oral availability of new lipophilic 9
      substituted camptothecin derivatives.
AB  - Despite that 9-substituted camptothecins are promising candidates in cancer
      therapy, the limited accessibility to this position has reduced the studies of
      these derivatives to a few standard modifications. We report herein a novel
      semisynthetic route based on the Tscherniac-Einhorn reaction to synthesize new
      lipophilic camptothecin derivatives with amidomethyl and imidomethyl
      substitutions in position 9. Compounds were evaluated for their antiproliferative
      activity, topoisomerase I inhibition, and oral availability. Preliminary data
      demonstrated that bulky imidomethyl modification is an appropriate lipophilic
      substitution for an effective oral administration relative to topotecan. In
      addition, this general procedure paves the way for obtaining new camptothecin
      derivatives. 

PMID- 24900726
TI  - Deconstruction of a nutlin: dissecting the binding determinants of a potent
      protein-protein interaction inhibitor.
AB  - Protein-protein interaction (PPI) systems represent a rich potential source of
      targets for drug discovery, but historically have proven to be difficult,
      particularly in the lead identification stage. Application of the fragment-based
      approach may help toward success with this target class. To provide an example
      toward understanding the potential issues associated with such an application, we
      have deconstructed one of the best established protein-protein inhibitors, the
      Nutlin series that inhibits the interaction between MDM2 and p53, into fragments,
      and surveyed the resulting binding properties using heteronuclear single quantum
      coherence nuclear magnetic resonance (HSQC NMR), surface plasmon resonance (SPR),
      and X-ray crystallography. We report the relative contributions toward binding
      affinity for each of the key substituents of the Nutlin molecule and show that
      this series could hypothetically have been discovered via a fragment approach. We
      find that the smallest fragment of Nutlin that retains binding accesses two
      subpockets of MDM2 and has a molecular weight at the high end of the range that
      normally defines fragments. 

PMID- 24900727
TI  - Tetrahydroquinoline-derived macrocyclic toolbox: the discovery of
      antiangiogenesis agents in zebrafish assay.
AB  - A novel approach to incorporate the macrocyclic rings onto the privileged
      substructure, i.e., tetrahydroquinoline scaffold, is developed. The presence of
      an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity
      to modulate the nature of the chiral side chain. Further, evaluation in a
      zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as
      antiangiogenesis agents at 2.5 MUM. 

PMID- 24900728
TI  - Synthesis of 2alpha-heteroarylalkyl active vitamin d3 with therapeutic effect on
      enhancing bone mineral density in vivo.
AB  - 2alpha-Heteroarylethyl-1alpha,25-dihydroxyvitamin D3 analogues, which were
      designed to form a hydrogen bond between Arg274 of human vitamin D receptor
      (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2alpha-position,
      were synthesized. Among them, 2alpha-[2-(tetrazol-2-yl)ethyl]-1alpha,25
      dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity
      in human osteosarcoma (HOS) cells and a greater therapeutic effect in
      ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral
      density than those of active vitamin D3. X-ray cocrystallographic analysis of the
      hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the
      complex. 

PMID- 24900729
TI  - Patent portfolios after myriad, how to fit in those new genes?
AB  - The recent US Supreme Court decision in Association for Molecular Pathology v.
      Myriad Genetics, Inc. clarified what is considered patentable subject matter.
      Patent claims limited to the composition of isolated nucleic acid sequences are
      now considered a product of nature and not patent eligible, while man-made
      variants of nucleic acid sequences may still be patentable. The decision is
      consistent with an earlier ruling in Mayo Collaborative Services v. Prometheus
      Laboratories., Inc. related to diagnostic methods. In Prometheus, the Court held
      that a method simply reciting known steps used to observe a natural event is not
      patentable subject matter. Taken together, the Court's decisions provide guidance
      as to what constitutes a natural phenomenon outside patent protection and what is
      considered a man-made creation worthy of protection. Despite misgivings, both
      decisions will provide impetus for increased genetic research and development of
      new therapeutics and diagnostics, especially in genomic and personalized
      medicine. 

PMID- 24900730
TI  - Inhibitors of the renal outer medullary potassium channel.

PMID- 24900731
TI  - Heteroaryl sodium channel inhibitors.

PMID- 24900732
TI  - Inhibitors of ATR Kinase for Treatment of Cancer.

PMID- 24900733
TI  - Inhibitors of Bruton's Tyrosine Kinase (Btk) May Treat Inflammation,
      Immunological Disorders, and Cancer.

PMID- 24900734
TI  - Histone Deacetylase 4 (HDAC4) Inhibitors: A Promising Treatment for Huntington's
      Disease.

PMID- 24900735
TI  - ABCB1 Structural Models, Molecular Docking, and Synthesis of New
      Oxadiazolothiazin-3-one Inhibitors.
AB  - Docking methods are powerful tools for in silico screening and drug lead
      generation and optimization. Here, we describe the synthesis of new inhibitors of
      ABCB1 whose design was based on construction and preliminary confirmation of a
      model for this membrane transporter of the ATP-binding cassette family. We chose
      the strategy to build our three-dimensional model of the ABCB1 transporter by
      homology. Atomic coordinates were then assayed for their reliability using the
      measured activity of some oxadiazolothiazin-3-one compounds. Once established
      their performance by docking analysis, we synthesized new compounds whose
      forecasted activity was tested by MTT and cytofluorimetric assays. Our docking
      model of MDR1, MONBD1, seems to reliably satisfy our need to design and forecast,
      on the basis of their LTCC blockers ability, the inhibitory activity of new
      molecules on the ABCB1 transporter. 

PMID- 24900736
TI  - Flow Synthesis and Biological Studies of an Analgesic Adamantane Derivative That
      Inhibits P2X7-Evoked Glutamate Release.
AB  - We report the biological evaluation of a class of adamantane derivatives, which
      were achieved via modified telescoped machine-assisted flow procedure. Among the
      series of compounds tested in this work, 5 demonstrated outstanding analgesic
      properties. This compound showed that its action was not mediated through direct
      interaction with opioid and/or cannabinoid receptors. Moreover, it did not
      display any significant anti-inflammatory properties. Experiments carried out on
      rat cerebrocortical purified synaptosomes indicated that 5 inhibits the P2X7
      evoked glutamate release, which may contribute to its antinociceptive properties.
      Nevertheless, further experiments are ongoing to characterize the pharmacological
      properties and mechanism of action of this molecule. 

PMID- 24900737
TI  - Design, synthesis, and evaluation of prodrugs of ertapenem.
AB  - Carbapenems are intravenous lifesaving hospital antibiotics. Once patients leave
      the hospital, they are sent home with antibiotics other than carbapenems since
      they cannot be administered orally due to lack of oral absorption primarily
      because of very highly polarity. A prodrug approach is a bona fide strategy to
      improve oral absorption of compounds. Design and synthesis, in vitro and in vivo
      evaluation of diversified prodrugs of ertapenem, one of the only once daily dosed
      carbapenems is described. Many of the prodrugs prepared for evaluation are
      rapidly hydrolyzed in rat plasma. Only bis-(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl
      (medoxomil) ester prodrug was rapidly hydrolyzed in most of the plasmas including
      rat, human, dog, and monkey. Although the rate of conversion of ertapenem diethyl
      ester prodrug (6) was slow in in vitro plasma hydrolysis, it showed the best in
      vivo pharmacokinetic profile in dog by an intraduodenal dosing giving >31% total
      oral absorption. 

PMID- 24900738
TI  - An optimized pyrimidinol multifunctional radical quencher.
AB  - A series of aza analogues (4-9) of the experimental neuroprotective drug
      idebenone (1) have been prepared and evaluated for their ability to attenuate
      oxidative stress induced by glutathione depletion and to compensate for the
      decrease in oxidative phosphorylation efficiency in cultured Friedreich's ataxia
      (FRDA) fibroblasts and lymphocytes and also coenzyme Q10-deficient lymphocytes.
      Modification of the redox core of the previously reported 3 improved its
      antioxidant and cytoprotective properties. Compounds 4-9, having the same redox
      core, exhibited a range of antioxidant activities, reflecting side chain
      differences. Compounds having side chains extending 14-16 atoms from the
      pyrimidinol ring (6, 7, and 9) were potent antioxidants. They were superior to
      idebenone and more active than 3, 4, 5, and 8. Optimized analogue 7 and its
      acetate (7a) are of interest in defining potential therapeutic agents capable of
      blocking oxidative stress, maintaining mitochondrial membrane integrity, and
      augmenting ATP levels. Compounds with such properties may find utility in
      treating mitochondrial and neurodegenerative diseases such as FRDA and
      Alzheimer's disease. 

PMID- 24900739
TI  - Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in
      Inhibition of NF-kappaB Activation.
AB  - A library of oxygenated natural steroids, including physalins, withanolides, and
      perulactones, coupled with the synthetic cage-shaped right-side structure of type
      B physalins, was constructed. SAR studies for inhibition of NF-kappaB activation
      showed the importance of both the B-ring and the oxygenated right-side partial
      structure. The 5beta,6beta-epoxy derivatives of both physalins and withanolides
      showed similar profiles of inhibition of NF-kappaB activation and appeared to act
      on NF-kappaB signaling via inhibition of phosphorylation and degradation of
      IkappaBalpha. In contrast, type B physalins with C5-C6 olefin functionality
      inhibited nuclear translocation and DNA binding of RelA/p50 protein dimer, which
      lie downstream of IkappaBalpha degradation, although withanolides having the same
      AB-ring functionality did not. These results indicated that the right-side
      partial structure of these steroids influences their mode of action. 

PMID- 24900740
TI  - Insights into the Importance of DFD-Motif and Insertion I1 in Stabilizing the DFD
      Out Conformation of Mnk2 Kinase.
AB  - Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2
      (Mnk1/2) are promising anticancer targets. Mnks possess special insertions and a
      DFD-motif that are distinct from other kinases. Crystallographic studies of
      Mnk1/2 have revealed that the DFD-motif adopts the DFG/D-out conformation in
      which residue F227 flips into the ATP binding pocket. This is rarely observed in
      other kinases. Although the DFG-out conformation has attracted great interest for
      designing selective inhibitors, structural requirements for binding and the
      mechanism governing the DFG-out conformation remain unclear. This work presents
      for the first time the applicability of 3D models of Mnk2 protein in studying
      conformational changes by utilizing homology modeling and molecular dynamics
      simulations. The study reveals that the interactions between residue K234 of
      insertion I1 and D226 of the DFD motif play a key role in inducing and
      stabilizing the DFD-out conformation. The structural features will aid in the
      rational design of Mnk2 inhibitors. 

PMID- 24900741
TI  - Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR,
      HER2, and HER3 Receptors.
AB  - Deregulation of HER family signaling promotes proliferation and tumor cell
      survival and has been described in many human cancers. Simultaneous, equipotent
      inhibition of EGFR-, HER2-, and HER3-mediated signaling may be of clinical
      utility in cancer settings where the selective EGFR or HER2 therapeutic agents
      are ineffective or only modestly active. We describe the discovery of AZD8931
      (2), an equipotent, reversible inhibitor of EGFR-, HER2-, and HER3-mediated
      signaling and the structure-activity relationships within this series. Docking
      studies based on a model of the HER2 kinase domain helped rationalize the
      increased HER2 activity seen with the methyl acetamide side chain present in
      AZD8931. AZD8931 exhibited good pharmacokinetics in preclinical species and
      showed superior activity in the LoVo tumor growth efficacy model compared to
      close analogues. AZD8931 is currently being evaluated in human clinical trials
      for the treatment of cancer. 

PMID- 24900742
TI  - Cyclodextrin complexed [60]fullerene derivatives with high levels of photodynamic
      activity by long wavelength excitation.
AB  - We have evaluated the photodynamic activities of C60 derivative.gamma
      cyclodextrin (gamma-CDx) complexes and demonstrated that they were significantly
      higher than those of the pristine C60 and C70.gamma-CDx complexes under
      photoirradiation at long wavelengths (610-720 nm), which represent the optimal
      wavelengths for photodynamic therapy (PDT). In particular, the cationic C60
      derivative.gamma-CDx complex had the highest photodynamic ability because the
      complex possessed the ability to generate high levels of (1)O2 and provided a
      higher level of intracellular uptake. The photodynamic activity of this complex
      was greater than that of photofrin, which is the most widely used of the known
      clinical photosensitizers. These findings therefore provide a significant level
      of information toward the optimization of molecular design strategies for the
      synthesis of fullerene derivatives for PDT. 

PMID- 24900743
TI  - Tropolones as lead-like natural products: the development of potent and selective
      histone deacetylase inhibitors.
AB  - Natural products have long been recognized as a rich source of potent
      therapeutics but further development is often limited by high structural
      complexity and high molecular weight. In contrast, at the core of the
      thujaplicins is a lead-like tropolone scaffold characterized by relatively low
      molecular weight, ample sites for diversification, and metal-binding
      functionality poised for targeting a range of metalloenzyme drug targets. Here,
      we describe the development of this underutilized scaffold for the discovery of
      tropolone derivatives that function as isozyme-selective inhibitors of the
      validated anticancer drug target, histone deacetylase (HDAC). Several
      monosubstituted tropolones display remarkable levels of selectivity for HDAC2 and
      potently inhibit the growth of T-cell lymphocyte cell lines. The tropolones
      represent a new chemotype of isozyme-selective HDAC inhibitors. 

PMID- 24900744
TI  - Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors:
      Application to Drug Discovery.
AB  - A novel integrated discovery platform has been used to synthesize and
      biologically assay a series of xanthine-derived dipeptidyl peptidase 4 (DPP4)
      antagonists. Design, synthesis, purification, quantitation, dilution, and
      bioassay have all been fully integrated to allow continuous automated operation.
      The system has been validated against a set of known DPP4 inhibitors and shown to
      give excellent correlation between traditional medicinal chemistry generated
      biological data and platform data. Each iterative loop of synthesis through
      biological assay took two hours in total, demonstrating rapid iterative structure
      activity relationship generation. 

PMID- 24900745
TI  - Potent DGAT1 Inhibitors in the Benzimidazole Class with a Pyridyl-oxy
      cyclohexanecarboxylic Acid Moiety.
AB  - We report the design and synthesis of a series of novel DGAT1 inhibitors in the
      benzimidazole class with a pyridyl-oxy-cyclohexanecarboxylic acid moiety. In
      particular, compound 11A is a potent DGAT1 inhibitor with excellent selectivity
      against ACAT1. Compound 11A significantly reduces triglyceride excursion in lipid
      tolerance tests (LTT) in both mice and dogs at low plasma exposure. An in vivo
      study in mice with des-fluoro analogue 10A indicates that this series of
      compounds appears to distribute in intestine preferentially over plasma. The
      propensity to target intestine over plasma could be advantageous in reducing
      potential side effects since lower circulating levels of drug are required for
      efficacy. However, in the preclinical species, compound 11A undergoes cis/trans
      epimerization in vivo, which could complicate further development due to the
      presence of an active metabolite. 

PMID- 24900746
TI  - Structural modification of pantothenamides counteracts degradation by
      pantetheinase and improves antiplasmodial activity.
AB  - Pantothenamides are secondary or tertiary amides of pantothenic acid, the vitamin
      precursor of the essential cofactor and universal acyl carrier coenzyme A. A
      recent study has demonstrated that pantothenamides inhibit the growth of blood
      stage Plasmodium falciparum with submicromolar potency by exerting an effect on
      pantothenic acid utilization, but only when the pantetheinase present in the
      growth medium has been inactivated. Here, we demonstrate that small modifications
      of the pantothenamide core structure are sufficient to counteract pantetheinase
      mediated degradation and that the resulting pantothenamide analogues still
      inhibit the in vitro proliferation of P. falciparum by targeting a pantothenic
      acid-dependent process (or processes). Finally, we investigated the toxicity of
      the most potent analogues to human cells and show that the selectivity ratio
      exceeds 100 in one case. Taken together, these results provide further support
      for pantothenic acid utilization being a viable target for antimalarial drug
      discovery. 

PMID- 24900747
TI  - Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for
      the Treatment of Type 2 Diabetes.
AB  - GPR142 is a G protein-coupled receptor that is predominantly expressed in
      pancreatic beta-cells. GPR142 agonists stimulate insulin secretion in the
      presence of high glucose concentration, so that they could be novel insulin
      secretagogues with reduced or no risk of hypoglycemia. We report here the
      optimization of HTS hit compound 1 toward a proof of concept compound 33, which
      showed potent glucose lowering effects during an oral glucose tolerance test in
      mice and monkeys. 

PMID- 24900748
TI  - Structural and biological exploration of phe(3)-phe(4)-modified endomorphin-2
      peptidomimetics.
AB  - This study reports on our ongoing investigation on hybrid EM-2 analogues, in
      which the great potential of beta-amino acids was exploited to generate multiple
      conformational modifications at the key positions 3 and 4 of the parent peptide.
      The effect on the opioid binding affinity was evaluated, by means of ligand
      stimulated binding assays, which indicated a high nanomolar affinity toward the
      MU-receptor, with appreciable MU/delta selectivity, for some of the new
      compounds. The three-dimensional properties of the high affinity MU opioid
      receptor (MOR) ligands were investigated by proton nuclear magnetic resonance,
      molecular dynamics, and docking studies. In solution, the structures showed
      extended conformations, which are in agreement with the commonly accepted
      pharmacophore model for EM-2. From docking studies on an active form of the MOR
      model, different ligand-receptor interactions have been identified, thus
      confirming the ability of active compounds to assume a biologically active
      conformation. 

PMID- 24900749
TI  - Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of
      CK2 Kinase with Activity in Vivo.
AB  - In this letter, we describe the design, synthesis, and structure-activity
      relationship of 5-anilinopyrazolo[1,5-a]pyrimidine inhibitors of CK2 kinase.
      Property-based optimization of early leads using the 7-oxetan-3-yl amino group
      led to a series of matched molecular pairs with lower lipophilicity, decreased
      affinity for human plasma proteins, and reduced binding to the hERG ion channel.
      Agents in this study were shown to modulate pAKT(S129), a direct substrate of
      CK2, in vitro and in vivo, and exhibited tumor growth inhibition when
      administered orally in a murine DLD-1 xenograft. 

PMID- 24900751
TI  - Inhibitors of PI3Kbeta as Potential Treatment for Cancer.

PMID- 24900750
TI  - Aminopyridyl/Pyrazinyl Spiro[indoline-3,4'-piperidine]-2-ones As Highly Selective
      and Efficacious c-Met/ALK Inhibitors.
AB  - A series of novel aminopyridyl/pyrazinyl-substituted spiro[indoline-3,4'
      piperidine]-2-ones were designed, synthesized, and tested in various in vitro/in
      vivo pharmacological and antitumor assays. 6-[6-Amino-5-[(1R)-1-(2,6-dichloro-3
      fluorophenyl)ethoxy]-3-pyridyl]-1'-methylspiro[indoline-3,4'-piperidine]-2-one
      (compound 5b or SMU-B) was identified as a potent, highly selective, well
      tolerated, and orally efficacious c-Met/ALK dual inhibitor, which showed
      pharmacodynamics effect by inhibiting c-Met phosphorylation in vivo and
      significant tumor growth inhibitions (>50%) in GTL-16 human gastric carcinoma
      xenograft models. 

PMID- 24900752
TI  - Imaging probes of tau pathology.

PMID- 24900753
TI  - Trisubstituted imidazoles as positive modulators of metabotropic glutamate
      receptor subtype 5.

PMID- 24900754
TI  - Substituted Benzylspiroindolin-2-one Analogues as Positive Allosteric Modulators
      of the Muscarinic Acetylcholine Receptor M1.

PMID- 24900755
TI  - Gamma secretase modulators.

PMID- 24900756
TI  - Designed Trpzip-3 beta-Hairpin Inhibits Amyloid Formation in Two Different
      Amyloid Systems.
AB  - The trpzip peptides are small, monomeric, and extremely stable beta-hairpins that
      have become valuable tools for studying protein folding. Here, we show that
      trpzip-3 inhibits aggregation in two very different amyloid systems:
      transthyretin and Abeta(1-42). Interestingly, Trp -> Leu mutations renders the
      peptide ineffective against transthyretin, but Abeta inhibition remains.
      Computational docking was used to predict the interactions between trpzip-3 and
      transthyretin, suggesting that inhibition occurs via binding to the outer region
      of the thyroxine-binding site, which is supported by dye displacement
      experiments. 

PMID- 24900757
TI  - Aminopyrazole-Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and
      in Vivo Efficacy Studies.
AB  - Herein, we report the lead optimization of amrinone-phenylalanine based GPR142
      agonists. Structure-activity relationship studies led to the discovery of
      aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic
      activity, high target selectivity, desirable pharmacokinetic properties, and no
      cytochrome P450 or hERG liability. Compound 22, together with its orally
      bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof
      of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose
      tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin
      secretion in isolated mouse islets and demonstrated a statistically significant
      glucose lowering effect in a mouse model bearing transplanted human islets. 

PMID- 24900759
TI  - Novel Macrocyclic Amidinoureas: Potent Non-Azole Antifungals Active against Wild
      Type and Resistant Candida Species.
AB  - Novel macrocyclic amidinourea derivatives 11, 18, and 25 were synthesized and
      evaluated as antifungal agents against wild-type and fluconazole resistant
      Candida species. Macrocyclic compounds 11 and 18 were synthesized through a
      convergent approach using as a key step a ring-closing metathesis
      macrocyclization reaction, whereas compounds 25 were obtained by our previously
      reported synthetic pathway. All the macrocyclic amidinoureas showed antifungal
      activity toward different Candida species higher or comparable to fluconazole and
      resulted highly active against fluconazole resistant Candida strains showing in
      many cases minimum inhibitory concentration values lower than voriconazole. 

PMID- 24900758
TI  - Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors.
AB  - The identification of a novel series of small molecule BET inhibitors is
      described. Using crystallographic binding modes of an amino-isoxazole fragment
      and known BET inhibitors, a structure-based drug design effort lead to a novel
      isoxazole azepine scaffold. This scaffold showed good potency in biochemical and
      cellular assays and oral activity in an in vivo model of BET inhibition. 

PMID- 24900760
TI  - Novel (64)Cu-Labeled CUDC-101 for in Vivo PET Imaging of Histone Deacetylases.
AB  - We report the design, synthesis, and biological evaluation of a (64)Cu-labeled
      histone deacetylase (HDAC) imaging probe, which was obtained by introduction of
      metal chelator through click reaction of HDAC inhibitor CUDC-101 and then
      radiolabeled with (64)Cu. The resulting (64)Cu-labeled compound 7 ([(64)Cu]7) was
      identified as a positron emission tomography (PET) imaging probe to noninvasively
      visualize HDAC expression in vivo. Cell based competitive assay established the
      specific binding of [(64)Cu]7 to HDACs. Biodistribution and small-animal
      microPET/CT studies further showed that [(64)Cu]7 had high tumor to background
      ratio in the MDA-MB-231 xenograft model, a triple-negative breast cancer with
      high expression of HDACs. To our knowledge, [(64)Cu]7 thus represents the first
      (64)Cu-labeled PET HDAC imaging probe, which exhibits nanomolar range binding
      affinity and capability to imaging HDAC expression in triple-negative breast
      cancer in vivo. 

PMID- 24900761
TI  - [(11)C]MK-4232: The First Positron Emission Tomography Tracer for the Calcitonin
      Gene-Related Peptide Receptor.
AB  - Rational modification of the potent calcitonin gene-related peptide (CGRP)
      receptor antagonist MK-3207 led to a series of analogues with enhanced CNS
      penetrance and a convenient chemical handle for introduction of a radiolabel. A
      number of (11)C-tracers were synthesized and evaluated in vivo, leading to the
      identification of [(11)C]8 ([(11)C]MK-4232), the first positron emission
      tomography tracer for the CGRP receptor. 

PMID- 24900763
TI  - Exploring multitarget interactions to reduce opiate withdrawal syndrome and
      psychiatric comorbidity.
AB  - Opioid addiction is often characterized as a chronic relapsing condition due to
      the severe somatic and behavioral signs, associated with depressive disorders,
      triggered by opiate withdrawal. Since prolonged abstinence remains a major
      challenge, our interest has been addressed to such objective. Exploring
      multitarget interactions, the present investigation suggests that 3 or its (S)
      enantiomer and 4, endowed with effective alpha2C-AR agonism/alpha2A-AR
      antagonism/5-HT1A-R agonism, or 7 and 9-11 producing efficacious alpha2C-AR
      agonism/alpha2A-AR antagonism/I2-IBS interaction might represent novel
      multifunctional tools potentially useful for reducing withdrawal syndrome and
      associated depression. Such agents, lacking in sedative side effects due to their
      alpha2A-AR antagonism, might afford an improvement over current therapies with
      clonidine-like drugs. 

PMID- 24900762
TI  - Inhibitors of tick-borne flavivirus reproduction from structure-based virtual
      screening.
AB  - Flaviviruses form a large family of enveloped viruses affecting millions of
      people over the world. To date, no specific therapy was suggested for the
      infected people, making the treatment exclusively symptomatic. Several attempts
      were performed earlier for the design of fusion inhibitors for mosquito-borne
      flaviviruses, whereas for the tick-borne flaviviruses such design had not been
      performed. We have constructed homology models of envelope glycoproteins of tick
      transmitted flaviviruses with the detergent binding pocket in the open state.
      Molecular docking of substituted 1,4-dihydropyridines and pyrido[2,1
      b][1,3,5]thiadiazines was made against these models, and 89 hits were selected
      for the in vitro experimental evaluation. Seventeen compounds showed significant
      inhibition against tick-borne encephalitis virus, Powassan virus, or Omsk
      hemorrhagic fever virus in the 50% plaque reduction test in PEK cells. These
      compounds identified through rational design are the first ones possessing
      reproduction inhibition activity against tick-borne flaviviruses. 

PMID- 24900765
TI  - Improving the plausibility of success with inefficient metrics.
AB  - To increase the probability of success in drug discovery, the concept of drug
      like properties was introduced. Efficiency metrics that normalize potency against
      these properties could help reach drug-like space more efficiently. Potential
      reasons for the inefficient use of metrics and suboptimal decision making are
      discussed. 

PMID- 24900764
TI  - MT-Stabilizer, Dictyostatin, Exhibits Prolonged Brain Retention and Activity:
      Potential Therapeutic Implications.
AB  - Inclusions comprising the microtubule (MT)-stabilizing protein, tau, are found
      within neurons in the brains of patients with Alzheimer's disease and related
      neurodegenerative disorders that are broadly referred to as tauopathies. The
      sequestration of tau into inclusions is believed to cause a loss of tau function,
      such that MT structure and function are compromised, leading to neuronal damage.
      Recent data reveal that the brain-penetrant MT-stabilizing agent, epothilone D
      (EpoD), improves cognitive function and decreases both neuron loss and tau
      pathology in transgenic mouse models of tauopathy. There is thus a need to
      identify additional MT-stabilizing compounds with blood-brain barrier (BBB)
      permeability and slow brain clearance, as observed with EpoD. We report here that
      the MT-stabilizing natural product, dictyostatin, crosses the BBB in mice and has
      extended brain retention. Moreover, a single administration of dictyostatin to
      mice causes prolonged stabilization of MTs in the brain. In contrast, the
      structurally related MT-stabilizer, discodermolide, shows significantly less
      brain exposure. Thus, dictyostatin merits further investigation as a potential
      tauopathy therapeutic. 

PMID- 24900766
TI  - Combatting resistant bacteria with the help of Beta-lactamase inhibitors.

PMID- 24900767
TI  - Inhibitors of Tropomyosin-Receptor Kinases (Trk's): Potential Pain Therapy and
      More.

PMID- 24900768
TI  - Tankyrase inhibitors: potential treatment of hyperproliferative diseases.

PMID- 24900769
TI  - Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi
      Phosphofructokinase.
AB  - Human African Trypanosomiasis (HAT) is a severe, often fatal disease caused by
      the parasitic protist Trypanosoma brucei. The glycolytic pathway has been
      identified as the sole mechanism for ATP generation in the infective stage of
      these organisms, and several glycolytic enzymes, phosphofructokinase (PFK) in
      particular, have shown promise as potential drug targets. Herein, we describe the
      discovery of ML251, a novel nanomolar inhibitor of T. brucei PFK, and the
      structure-activity relationships within the series. 

PMID- 24900770
TI  - Evaluation and Structural Basis for the Inhibition of Tankyrases by PARP
      Inhibitors.
AB  - Tankyrases, an enzyme subfamily of human poly(ADP-ribosyl)polymerases, are
      potential drug targets especially against cancer. We have evaluated inhibition of
      tankyrases by known PARP inhibitors and report five cocrystal structures of the
      most potent compounds in complex with human tankyrase 2. The inhibitors include
      the small general PARP inhibitors Phenanthridinone, PJ-34, and TIQ-A as well as
      the more advanced inhibitors EB-47 and rucaparib. The compounds anchor to the
      nicotinamide subsite of tankyrase 2. Crystal structures reveal flexibility of the
      ligand binding site with implications for drug development against tankyrases and
      other ADP-ribosyltransferases. EB-47 mimics the substrate NAD(+) and extends from
      the nicotinamide to the adenosine subsite. The clinical ARTD1 inhibitor candidate
      rucaparib was the most potent tankyrase inhibitor identified (24 and 14 nM for
      tankyrases), which indicates that inhibition of tankyrases would affect the
      cellular responses of this compound. 

PMID- 24900771
TI  - Dendrimer Conjugate of [4-(Tetradecanoylamino)benzyl]phosphonic Acid (S32826) as
      an Autotaxin Inhibitor.
AB  - Autotaxin is an extracellular phospholipase D that catalyzes the hydrolysis of
      lysophosphatidyl choline (LPC) to bioactive lipid lysophosphatidic acid (LPA).
      LPA has been implicated in many pathological processes relevant to cancer,
      including cell migration and invasion, proliferation, and survival. The most
      potent autotaxin inhibitor described to date is the LPA analogue S32826 (IC50 5.6
      nM). S32826 and many other autotaxin inhibitors are notably lipophilic, creating
      a need to improve their physical properties. Polymers are becoming an
      increasingly useful tool in the delivery of drugs and have the potential to
      improve the properties of small molecules. Herein we report the synthesis of a
      S32826 dendrimer conjugate and its biological evaluation. The conjugate was found
      to inhibit autotaxin activity using two different substrates and to decrease the
      migration of an ovarian cancer cell line modified to overexpress autotaxin.
      Furthermore, the conjugate potentiated activation of caspase 3/7 induced by
      carboplatin. 

PMID- 24900772
TI  - Thioester Bonds of Thiocoraline Can Be Replaced with NMe-Amide Bridges without
      Affecting Its DNA-Binding Properties.
AB  - In the search for new drug candidates for DNA recognition, affinity and sequence
      selectivity are two of the most important features. NMe-azathiocoraline, a
      synthetic antitumor bisintercalator derived from the natural marine product
      thiocoraline, shows similar potency to the parent compound, as well as possessing
      enhanced stability. Analysis of the DNA-binding selectivity of NMe
      azathiocoraline by DNase I footprinting using universal substrates with all 136
      tetranucleotides and all possible symmetrical hexanucleotide sequences revealed
      that, although this ligand binds to all CpG steps with lower affinities than
      thiocoraline, it displays additional binding to AT-rich sites. Moreover,
      fluorescence melting studies showed a strong interaction of the synthetic
      molecule with CACGTG and weaker binding to ACATGT and AGATCT. These findings
      demonstrate that NMe-azathiocoraline has the same mode of action as thiocoraline,
      mimicking its DNA-binding selectivity despite the substitution of its thioester
      bonds by NMe-amide bridges. 

PMID- 24900773
TI  - Novel Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor
      for Treatment of Type 2 Diabetes.
AB  - Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary
      glucose excretion (UGE) and thus reduces blood glucose levels during
      hyperglycemia. To explore the potential of new antihyperglycemic agents, we
      synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel
      substituted 3-benzylindole-N-glucosides 6. Optimization of 6 resulted in the
      discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a
      highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic
      effects in high-fat diet-fed KK (HF-KK) mice. Our results suggest the potential
      of indole-N-glucosides as novel antihyperglycemic agents through inhibition of
      renal SGLT2. 

PMID- 24900774
TI  - Discovery of Tertiary Amine and Indole Derivatives as Potent RORgammat Inverse
      Agonists.
AB  - A novel series of tertiary amines as retinoid-related orphan receptor gamma-t
      (RORgammat) inverse agonists was discovered through agonist/inverse agonist
      conversion. The level of RORgammat inhibition can be enhanced by modulating the
      conformational disruption of H12 in RORgammat LBD. Linker exploration and
      rational design led to the discovery of more potent indole-based RORgammat
      inverse agonists. 

PMID- 24900775
TI  - Synthesis and in Vitro Evaluation of a Peptidomimetic Inhibitor Targeting the Src
      Homology 2 (SH2) Domain of STAT6.
AB  - An improved synthesis of a phosphopeptidomimetic prodrug targeting the Src
      Homology 2 (SH2) domain of signal transducer and activator of transcription 6
      (STAT6) is reported. In our convergent methodology, we employed a phosphotyrosine
      surrogate active ester harboring pivaloyloxymethyl groups, which efficiently
      coupled to tert-butylglycinyl proline diarylamide. Biological evaluation of 1 has
      not been reported. We show that it inhibits STAT6 phosphorylation in intact human
      bronchial epithelial cells, suggesting potential application in the treatment of
      asthma. 

PMID- 24900777
TI  - Identification of a new scaffold for hsp90 C-terminal inhibition.
AB  - Inhibition of Hsp90 C-terminal function is an advantageous therapeutic paradigm
      for the treatment of cancer. Currently, the majority of Hsp90 C-terminal
      inhibitors are derived from novobiocin, a natural product traditionally used as
      an antibiotic. Assisted by molecular docking studies, a scaffold containing a
      biphenyl moiety in lieu of the coumarin ring system found in novobiocin was
      identified for development of new Hsp90 C-terminal inhibitors. Initial structure
      activity studies led to derivatives that manifest good antiproliferative activity
      against two breast cancer cell lines through Hsp90 inhibition. This platform
      serves as a scaffold upon which new Hsp90 C-terminal inhibitors can be readily
      assembled for further investigation. 

PMID- 24900776
TI  - Discovery of a Novel Class of Imidazo[1,2-a]Pyridines with Potent PDGFR Activity
      and Oral Bioavailability.
AB  - The in silico construction of a PDGFRbeta kinase homology model and ensuing
      medicinal chemistry guided by molecular modeling, led to the identification of
      potent, small molecule inhibitors of PDGFR. Subsequent exploration of structure
      activity relationships (SAR) led to the incorporation of a constrained secondary
      amine to enhance selectivity. Further refinements led to the integration of a
      fluorine substituted piperidine, which resulted in significant reduction of P
      glycoprotein (Pgp) mediated efflux and improved bioavailability. Compound 28
      displayed oral exposure in rodents and had a pronounced effect in a
      pharmacokinetic-pharmacodynamic (PKPD) assay. 

PMID- 24900778
TI  - Evaluation of aminohydantoins as a novel class of antimalarial agents.
AB  - Given the threat of drug resistance, there is an acute need for new classes of
      antimalarial agents that act via a unique mechanism of action relative to
      currently used drugs. We have identified a set of druglike compounds within the
      Tres Cantos Anti-Malarial Set (TCAMS) which likely act via inhibition of a
      Plasmodium aspartic protease. Structure-activity relationship analysis and
      optimization of these aminohydantoins demonstrate that these compounds are potent
      nanomolar inhibitors of the Plasmodium aspartic proteases PM-II and PM-IV and
      likely one or more other Plasmodium aspartic proteases. Incorporation of a bulky
      group, such as a cyclohexyl group, on the aminohydantion N-3 position gives
      enhanced antimalarial potency while reducing inhibition of human aspartic
      proteases such as BACE. We have identified compound 8p (CWHM-117) as a promising
      lead for optimization as an antimalarial drug with a low molecular weight, modest
      lipophilicity, oral bioavailability, and in vivo antimalarial activity in mice. 

PMID- 24900779
TI  - (S)-N-Methyldihydroquinazolinones are the Active Enantiomers of Retro-2 Derived
      Compounds against Toxins.
AB  - This study reports the synthesis, chromatographic separation, and pharmacological
      evaluation of the two enantiomers of a new compound, named Retro-2.1, active
      against toxins by inhibiting intracellular trafficking via the retrograde route.
      The absolute configuration of the bioactive enantiomer has been assigned from X
      ray diffraction to the (S)-enantiomer. To date, (S)-Retro-2.1 is the most potent
      molecule to counteract the cytotoxic potential of ricin and Shiga toxin, with
      EC50 values of 23 and 54 nM, respectively. 

PMID- 24900780
TI  - Spotlight on fluorescent biosensors-tools for diagnostics and drug discovery.
AB  - Fluorescent biosensors constitute potent tools for probing biomolecules in their
      natural environment and for visualizing dynamic processes in complex biological
      samples, living cells, and organisms. They are well suited for highlighting
      molecular alterations associated with pathological disorders, thereby offering
      means of implementing sensitive and alternative technologies for diagnostic
      purposes. They constitute attractive tools for drug discovery programs, from high
      throughput screening assays to preclinical studies. 

PMID- 24900782
TI  - Ethoxysanguinarine Induces Inhibitory Effects and Downregulates CIP2A in Lung
      Cancer Cells.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is
      able to stabilize c-Myc oncogenic transcription factor and promote proliferation
      and transformation of cells. CIP2A is overexpressed in many primary tumors, and
      pharmacological inactivation of CIP2A is an emerging concept for the development
      of novel anticancer agents. In this study, we demonstrate that overexpression of
      CIP2A predicts poor prognosis in lung cancer, and a natural compound,
      ethoxysanguinarine (ESG), effectively downregulates CIP2A protein and its
      downstream signaling molecules, c-Myc and pAkt, and induces protein phosphatase
      2A (PP2A) activity. ESG inhibits proliferation and induces apoptosis of lung
      cancer cells, and enhances the effects of cisplatin on malignant cells. Taken
      together, our findings demonstrate that CIP2A is inversely associated with the
      clinical outcome of lung cancer, and ESG can serve as a lead compound for the
      development of CIP2A inhibitor for cancer therapies. 

PMID- 24900781
TI  - Novel endoperoxide-based transmission-blocking antimalarials with liver- and
      blood-schizontocidal activities.
AB  - In a search for effective compounds against both the blood- and liver-stages of
      infection by malaria parasites with the ability to block the transmission of the
      disease to mosquito vectors, a series of hybrid compounds combining either a
      1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were
      synthesized and screened for their antimalarial activity. These hybrid compounds
      showed high potency against both exoerythrocytic and erythrocytic forms of
      malaria parasites, comparable to representative trioxane-based counterparts.
      Furthermore, they efficiently blocked the development of the sporogonic cycle in
      the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker
      between the two moieties, effectively cleared a patent blood-stage P. berghei
      infection in mice after i.p. administration. Overall, these results indicate that
      peroxide-8-aminoquinoline hybrids are excellent starting points to develop an
      agent that conveys all the desired antimalarial multistage activities in a single
      chemical entity and, as such, with the potential to be used in malaria
      elimination campaigns. 

PMID- 24900783
TI  - Qualification of LSP1-2111 as a Brain Penetrant Group III Metabotropic Glutamate
      Receptor Orthosteric Agonist.
AB  - LSP1-2111 is a group III metabotropic glutamate receptor agonist with preference
      toward the mGlu4 receptor subtype. This compound has been extensively used as a
      tool to explore the pharmacology of mGlu4 receptor activation in preclinical
      animal behavioral models. However, the blood-brain barrier penetration of this
      amino acid derivative has never been studied. We report studies on the central
      nervous system (CNS) disposition of LSP1-2111 using quantitative microdialysis in
      rat. Significant unbound concentrations of the drug relative to its in vitro
      binding affinity and functional potency were established in extracellular fluid
      (ECF). These findings support the use of LSP1-2111 to study the CNS pharmacology
      of mGlu4 receptor activation through orthosteric agonist mechanisms. 

PMID- 24900784
TI  - Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for
      Potential Clinical Development.
AB  - The development of small-molecule MDM2 inhibitors to restore dysfunctional p53
      activities represents a novel approach for cancer treatment. In a previous
      communication, the efforts leading to the identification of a non-imidazoline
      MDM2 inhibitor, RG7388, was disclosed and revealed the desirable in vitro and in
      vivo pharmacological properties that this class of pyrrolidine-based inhibitors
      possesses. Given this richness and the critical need for a wide variety of
      chemical structures to ensure success in the clinic, research was expanded to
      evaluate additional derivatives. Here we report two new potent, selective, and
      orally active p53-MDM2 antagonists, RO5353 and RO2468, as follow-ups with
      promising potential for clinical development. 

PMID- 24900785
TI  - Isomannide-based peptidomimetics as inhibitors for human tissue kallikreins 5 and
      7.
AB  - Human kallikrein 5 (KLK5) and 7 (KLK7) are potential targets for the treatment of
      skin inflammation and cancer. Previously, we identified isomannide derivatives as
      potent and competitive KLK7 inhibitors. The introduction of N-protected amino
      acids into the isomannide-based scaffold was studied. Some KLK5 inhibitors with
      submicromolar affinity (K i values of 0.3-0.7 MUM) were identified, and they were
      6- to 13-fold more potent than our previous hits. Enzyme kinetics studies and the
      determination of the mechanism of inhibition confirmed that the new isomannide
      based derivatives are competitive inhibitors of both KLK5 and KLK7. Molecular
      docking and MD simulations of selected inhibitors into the KLK5 binding site
      provide insight into the molecular mechanism by which these compounds interact
      with the enzyme. The promising results obtained in this study open new prospects
      on the design and synthesis of highly specific KLK5 and KLK7 inhibitors. 

PMID- 24900786
TI  - Crystal Structures of PI3Kalpha Complexed with PI103 and Its Derivatives: New
      Directions for Inhibitors Design.
AB  - The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles
      in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently
      found in a wide variety of human cancers, validating it as a promising target for
      cancer therapy. We determined the crystal structure of the human PI3Kalpha-PI103
      complex to unravel molecular interactions. Based on the structure, substitution
      at the R1 position of the phenol portion of PI103 was demonstrated to improve
      binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP
      catalytic site. Interestingly, the crystal structure of the PI3Kalpha-9d complex
      revealed that the flexibility of Lys802 can also induce additional space at the
      catalytic site for further modification. Thus, these crystal structures provide a
      molecular basis for the strong and specific interactions and demonstrate the
      important role of Lys802 in the design of novel PI3Kalpha inhibitors. 

PMID- 24900787
TI  - Design, synthesis, and osteogenic activity of daidzein analogs on human
      mesenchymal stem cells.
AB  - Osteoporosis is caused by an overstimulation of osteoclast activity and the
      destruction of the bone extracellular matrix. Without the normal architecture,
      osteoblast cells are unable to rebuild phenotypically normal bone. Hormone
      replacement therapy with estrogen has been effective in increasing osteoblast
      activity but also has resulted in the increased incidence of breast and uterine
      cancer. In this study we designed and synthesized a series of daidzein analogs to
      investigate their osteogenic induction potentials. Human bone marrow derived
      mesenchymal stem cells (MSCs) from three different donors were treated with
      daidzein analogs and demonstrated enhanced osteogenesis when compared to daidzein
      treatment. The enhanced osteogenic potential of these daidzein analogs resulted
      in increased osterix (Sp7), alkaline phosphatase (ALP), osteopontin (OPN), and
      insulin-like growth factor 1 (IGF-1), which are osteogenic transcription factors
      that regulate the maturation of osteogenic progenitor cells into mature
      osteoblast cells. 

PMID- 24900788
TI  - Diversity-oriented synthesis yields a new drug lead for treatment of chagas
      disease.
AB  - A phenotypic high-throughput screen using ~100,000 compounds prepared using
      Diversity-Oriented Synthesis yielded stereoisomeric compounds with nanomolar
      growth-inhibition activity against the parasite Trypanosoma cruzi, the
      etiological agent of Chagas disease. After evaluating stereochemical dependence
      on solubility, plasma protein binding and microsomal stability, the SSS analogue
      (5) was chosen for structure-activity relationship studies. The p-phenoxy benzyl
      group appended to the secondary amine could be replaced with halobenzyl groups
      without loss in potency. The exocyclic primary alcohol is not needed for activity
      but the isonicotinamide substructure is required for activity. Most importantly,
      these compounds are trypanocidal and hence are attractive as drug leads for both
      acute and chronic stages of Chagas disease. Analogue (5) was nominated as the
      molecular libraries probe ML341 and is available through the Molecular Libraries
      Probe Production Centers Network. 

PMID- 24900789
TI  - Neutral beta-Lactams Inactivate High Molecular Mass Penicillin-Binding Proteins
      of Class B1, Including PBP2a of MRSA.
AB  - The targets of beta-lactam antibiotics are bacterial DD-peptidases (penicillin
      binding proteins). beta-Lactam SAR studies over many years have demonstrated the
      importance of a specifically placed negative charge, usually carboxylate, on
      these molecules. We show here that neutral analogues of classical beta-lactam
      antibiotics are of comparable activity to the originals against beta-lactam
      resistant high molecular mass DD-peptidases of the B1 class, a group that
      includes PBP2a of methicillin-resistant Staphylococcus aureus. These neutral beta
      lactams may direct new development of antibiotics against certain penicillin
      resistant bacteria. These molecules do have antibiotic activity against Gram
      positive bacteria. 

PMID- 24900791
TI  - Replacement of the Disulfide Bridge in a KLK3-Stimulating Peptide Using
      Orthogonally Protected Building Blocks.
AB  - Peptide "B-2", which is one of the most potent kallikrein-related peptidase 3
      (KLK3)-stimulating compounds, consists of 12 amino acids and is cyclized by a
      disulfide bridge between the N- and C-terminal cysteines. Orthogonally protected
      building blocks were used in the peptide synthesis to introduce a disulfide
      bridge mimetic consisting of four carbon atoms. The resulting pseudopeptides with
      alkane and E-alkene linkers doubled the proteolytic activity of KLK3 at a
      concentration of 14 MUM. They were almost as potent as the parent "B-2" peptide,
      which gives a 3.6-fold increase in the proteolytic activity of KLK3 at the same
      concentration. 

PMID- 24900790
TI  - Original Design of Fluorescent Ligands by Fusing BODIPY and Melatonin
      Neurohormone.
AB  - An original design and synthesis of fluorescent ligands for melatonin receptor
      studies is presented and consists in the fusion of the endogenous ligand with the
      fluorescent BODIPY core. Probes I-IV show high affinities for MT1 and MT2
      melatonin receptors and exhibit fluorescence properties compatible with cell
      observation. 

PMID- 24900792
TI  - FGFR1 Kinase Inhibitors: Close Regioisomers Adopt Divergent Binding Modes and
      Display Distinct Biophysical Signatures.
AB  - The binding of a ligand to its target protein is often accompanied by
      conformational changes of both the protein and the ligand. This is of particular
      interest, since structural rearrangements of the macromolecular target and the
      ligand influence the free energy change upon complex formation. In this study, we
      use X-ray crystallography, isothermal titration calorimetry, and surface-plasmon
      resonance biosensor analysis to investigate the binding of
      pyrazolylaminopyrimidine inhibitors to FGFR1 tyrosine kinase, an important
      anticancer target. Our results highlight that structurally close analogs of this
      inhibitor series interact with FGFR1 with different binding modes, which are a
      consequence of conformational changes in both the protein and the ligand as well
      as the bound water network. Together with the collected kinetic and thermodynamic
      data, we use the protein-ligand crystal structure information to rationalize the
      observed inhibitory potencies on a molecular level. 

PMID- 24900793
TI  - Functionally Optimized Neuritogenic Farinosone C Analogs: SAR-Study and
      Investigations on Their Mode of Action.
AB  - Several natural products derived from entomopathogenic fungi have been shown to
      initiate neuronal differentiation in the rat pheochromocytoma PC12 cell line.
      After the successful completion of the total synthesis program, the reduction of
      structural complexity while retaining biological activity was targeted. In this
      study, farinosone C served as a lead structure and inspired the preparation of
      small molecules with reduced complexity, of which several were able to induce
      neurite outgrowth. This allowed for the elaboration of a detailed structure
      activity relationship. Investigations on the mode of action utilizing a
      computational similarity ensemble approach suggested the involvement of the
      endocannabinoid system as potential target for our analogs and also led to the
      discovery of four potent new endocannabinoid transport inhibitors. 

PMID- 24900794
TI  - Total synthesis of thiaplakortone a: derivatives as metabolically stable leads
      for the treatment of malaria.
AB  - Thiaplakortone A (3a), an antimalarial natural product, was prepared by an
      operationally simple and scalable synthesis. In our efforts to deliver a lead
      compound with improved potency, metabolic stability, and selectivity, the
      synthesis was diverted to access a series of analogues. Compounds 3a-d showed
      nanomolar activity against the chloroquine-sensitive (3D7) Plasmodium falciparum
      line and were more active against the chloroquine- and mefloquine-resistant (Dd2)
      P. falciparum line. All compounds are "Rule-of-5" compliant, and we show that
      metabolic stability can be enhanced via modification at either the primary or
      pyrrole nitrogen. These promising results lay the foundation for the development
      of this structurally unprecedented natural product. 

PMID- 24900795
TI  - Himbacine-derived thrombin receptor antagonists: c7-aminomethyl and c9a-hydroxy
      analogues of vorapaxar.
AB  - We have synthesized several C7-aminomethyl analogues of vorapaxar that are potent
      PAR-1 antagonists. Many of these analogues showed excellent in vitro binding
      affinity and pharmacokinetics profile in rats. Compound 6a from this series
      showed excellent PAR-1 activity (K i = 5 nM). We have also synthesized a C9a
      hydroxy analogue of vorapaxar, which showed very good PAR-1 affinity (K i = 19.5
      nM) along with excellent rat pharmacokinetic profile and ex vivo efficacy in the
      cynomolgus monkey. 

PMID- 24900797
TI  - HIV Integrase Inhibitors for Treatment of HIV Infections and AIDS.

PMID- 24900796
TI  - Design and Synthesis of Phenylpyrrolidine Phenylglycinamides As Highly Potent and
      Selective TF-FVIIa Inhibitors.
AB  - Inhibitors of the Tissue Factor/Factor VIIa (TF-FVIIa) complex are promising
      novel anticoagulants that show excellent efficacy and minimal bleeding in
      preclinical models. On the basis of a zwitterionic phenylglycine acylsulfonamide
      1, a phenylglycine benzylamide 2 was shown to possess improved permeability and
      oral bioavailability. Optimization of the benzylamide, guided by X-ray
      crystallography, led to a potent TF-FVIIa inhibitor 18i with promising oral
      bioavailability, but promiscuous activity in an in vitro safety panel of
      receptors and enzymes. Introducing an acid on the pyrrolidine ring, guided by
      molecular modeling, resulted in highly potent, selective, and efficacious TF
      FVIIa inhibitors with clean in vitro safety profile. The pyrrolidine acid 20
      showed a moderate clearance, low volume of distribution, and a short t 1/2 in dog
      PK studies. 

PMID- 24900798
TI  - Selective EP4 Antagonist May Be Useful in Treating Arthritis and Arthritic Pain.

PMID- 24900799
TI  - Inhibitors of factor d may provide a treatment for age-related macular
      degeneration.

PMID- 24900800
TI  - Small Macrocycles As Highly Active Integrin alpha2beta1 Antagonists.
AB  - Starting from clinical candidates Firategrast, Valategrast, and AJM-300, a series
      of novel macrocyclic platelet collagen receptor alpha2beta1 antagonists were
      developed. The amino acid derived low molecular weight 14-18-membered macrocycles
      turned out to be highly active toward integrin alpha2beta1 with IC50s in the low
      nanomolar range. The conformation of the macrocycles was found to be highly
      important for the activity, and an X-ray crystal structure was obtained to
      clarify this. Subsequent docking into the metal-ion-dependent adhesion site
      (MIDAS) of a beta1 unit revealed a binding model indicating key binding features.
      Macrocycle 38 was selected for further in vitro and in vivo profiling. 

PMID- 24900802
TI  - Substituted imidazothiazoles as inhibitors of viral polymerase.

PMID- 24900801
TI  - Discovery and development of potent and selective inhibitors of histone
      methyltransferase g9a.
AB  - G9a is a histone lysine methyltransferase responsible for the methylation of
      histone H3 lysine 9. The discovery of A-366 arose from a unique diversity
      screening hit, which was optimized by incorporation of a propyl-pyrrolidine
      subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a
      (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other
      methyltransferases. 

PMID- 24900803
TI  - Substituted Benzofurans as Inhibitors of HCV NS5B Protein.

PMID- 24900804
TI  - Inhibitors of NS5A for Treatment of HCV Infection.

PMID- 24900805
TI  - Aminoquinoline derivatives as HCV inhibitors.

PMID- 24900806
TI  - Pyridopyrimidines as inhibitors of hepatitis C virus.

PMID- 24900807
TI  - 2',4'-Difluoro-2'-methyl Substituted Nucleoside Derivatives as Inhibitors of HCV
      RNA Replication.

PMID- 24900808
TI  - Antiviral compounds for the treatment of HCV.

PMID- 24900809
TI  - HCV polymerase inhibitors.

PMID- 24900810
TI  - Halting HCV Replication with NS5A Inhibitors and NS5B Polymerase Inhibitors:
      Effective New Treatments of HCV Infection.

PMID- 24900811
TI  - Discovery of Thienoimidazole-Based HCV NS5A Genotype 1a and 1b Inhibitors.
AB  - The discovery of potent thienoimidazole-based HCV NS5A inhibitors is herein
      reported. A novel method to access the thienoimidazole [5,5]-bicyclic system is
      disclosed. This method gave access to a common key intermediate (6) that was
      engaged in Suzuki or Sonogashira reactions with coupling partners bearing
      different linkers. A detailed study of the structure-activity relationship (SAR)
      of the linkers revealed that aromatic linkers with linear topologies are required
      to achieve high potency for both 1a and 1b HCV genotypes. Compound 20, with a
      para-phenyl linker, was identified as a potential lead displaying potencies of 17
      and 8 pM against genotype 1a and 1b replicons, respectively. 

PMID- 24900812
TI  - Discovery of SCH 900188: A Potent Hepatitis C Virus NS5B Polymerase Inhibitor
      Prodrug As a Development Candidate.
AB  - Starting from indole-based hepatitis C virus (HCV) NS5B polymerase inhibitor lead
      compound 1, structure modifications were performed at multiple indole
      substituents to improve potency and pharmacokinetic (PK) properties. Bicyclic
      quinazolinone was found to be the best substituent at indole nitrogen, while 4,5
      furanylindole was identified as the best core. Compound 11 demonstrated excellent
      potency. Its C2 N,N-dimethylaminoethyl ester prodrug 12 (SCH 900188) demonstrated
      significant improvement in PK and was selected as the development candidate. 

PMID- 24900813
TI  - Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2
      P1' Region.
AB  - Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2
      pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl
      acyl sulfonamide functionality in P1 are presented. The P1' 4
      (trifluoromethyl)phenyl side chain was shown to be particularly beneficial in
      terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar
      range were developed and included identification of promising P3-truncated
      inhibitors spanning from P2-P1'. Of several different P2 capping groups that were
      evaluated, a preference for the sterically congested Boc group was revealed. The
      inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K
      variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed
      several beneficial effects on metabolic stability as well as on apparent
      intestinal permeability from both P3 truncation and the use of the P1' 4
      (trifluoromethyl)phenyl side chain. 

PMID- 24900816
TI  - Evolving therapies for the treatment of HCV viral hepatitis.

PMID- 24900817
TI  - Triazine Analogues as NS5B Inhibitors for the Treatment of HCV.

PMID- 24900815
TI  - Synthesis and Anti-HCV Activity of 4-Hydroxyamino alpha-Pyranone Carboxamide
      Analogues.
AB  - High genetic variability in hepatitis C virus (HCV), emergence of drug resistant
      viruses and side effects demand the requirement for development of new scaffolds
      to show an alternate mechanism. Herein, we report discovery of new scaffold I
      based on 4-hydroxyamino alpha-pyranone carboxamide as promising anti-HCV agents.
      A comprehensive structure-activity relationship (SAR) was explored with several
      newly synthesized compounds. In all promising compounds (17-19, 21-22, 24-25, and
      49) with EC50 ranging 0.15 to 0.40 MUM, the aryl group at C-6 position of alpha
      pyranone were unsubstituted. In particular, 25 demonstrated potential anti-HCV
      activity with EC50 of 0.18 MUM in cell based HCV replicon system with lower
      cytotoxicity (CC50 > 20 MUM) and provided a new scaffold for anti-HCV drug
      development. Further investigations, including biochemical characterization, are
      yet to be performed to elucidate its possible mode of action. 

PMID- 24900814
TI  - Potent Hepatitis C Virus NS5A Inhibitors Containing a Benzidine Core.
AB  - Here we report the discovery of a series of potent hepatitis C virus (HCV) NS5A
      inhibitors based on the benzidine prolinamide backbone. Taking a simple synthetic
      route, we developed a novel inhibitor structure, which allows easy modification,
      and through optimization of the capping group, we identified compound 6 with
      highly potent anti-HCV activity. Compound 6 is nontoxic and is anticipated to be
      an effective HCV drug candidate. 

PMID- 24900819
TI  - New frontiers in kinases: special issue.

PMID- 24900818
TI  - Novel Quinoline-Based P2-P4 Macrocyclic Derivatives As Pan-Genotypic HCV NS3/4a
      Protease Inhibitors.
AB  - We have previously reported the discovery of our P2-P4 macrocyclic HCV NS3/4a
      protease inhibitor MK-5172, which in combination with the NS5a inhibitor MK-8742
      recently received a breakthrough therapy designation from the US FDA for
      treatment of chronic HCV infection. Our goal for the next generation NS3/4a
      inhibitor was to achieve pan-genotypic activity while retaining the
      pharmacokinetic profile of MK-5172. One of the areas for follow-up investigation
      involved replacement of the quinoxaline moiety in MK-5172 with a quinoline and
      studying the effect of substitution at 4-position of the quinoline. The rationale
      for this effort was based on molecular modeling, which indicated that such
      modifications would improve interactions with the S2 subsite, in particular with
      D79. We wish to report herein the discovery of highly potent inhibitors with pan
      genotypic activity and an improved profile over MK-5172, especially against gt-3a
      and A156 mutants. 

PMID- 24900820
TI  - A new challenging and promising era of tyrosine kinase inhibitors.
AB  - Protein kinases are key regulators that govern complex cellular processes.
      Dysregulation of kinase signaling is associated in many human diseases,
      particularly cancers and developmental and metabolic disorders. Tyrosine kinase
      inhibitors have achieved great success in molecular targeted therapies for cancer
      and now is expanding to other therapeutic areas. The onset of drug resistance to
      prolonged TKI treatment brings new challenges in TKI drug development. The deep
      understanding of disease pathologies related to TKs and drug resistance
      mechanisms will generate new waves for seeking highly selective, potent, and safe
      TKIs. 

PMID- 24900821
TI  - Quinoline Derivatives as 5-HT6 Receptor PET Ligands.

PMID- 24900822
TI  - Thiazolocarboxamide Analogues as NAMPT Inhibitors.

PMID- 24900823
TI  - Phenyl carboxamide analogues as spleen tyrosine kinase (syk) inhibitors.

PMID- 24900824
TI  - Novel cycloalkenepyrazoles as inhibitors of bub1 kinase.

PMID- 24900825
TI  - Triazolo[4,5-d]pyrimidine Derivatives as Inhibitors of GCN2.

PMID- 24900826
TI  - Selective 5-HT Receptor Modulators May Deliver Focused Targeting with Fewer
      Adverse Effects.

PMID- 24900827
TI  - Inhibitors of Factor XIa and Plasma Kallikrein May Treat Thromboembolic Disorders
      and Many Diabetes Complications.

PMID- 24900828
TI  - Liver S9 Fraction-Derived Metabolites of Curcumin Analogue UBS109.
AB  - To address the shortcomings of the natural product curcumin, many groups have
      created analogues that share similar structural features while displaying
      superior properties, particularly in anticancer drug discovery. Relatively
      unexplored have been the mechanisms by which such compounds are metabolized. A
      comprehensive in vitro study of a curcumin analogue (UBS109) in liver S9
      fractions from five different species is presented. Further, we examine the cell
      based bioactivity of the major metabolites. In spite of the fact that UBS109
      reduces tumor growth in mice, it is quickly metabolized in vitro and 94% protein
      bound in mouse plasma. The primary monounsaturated metabolite is only modestly
      bioactive against MDA-MB-231 breast cancer cells. These observations suggest that
      while the alpha,beta-unsaturated ketone common to curcumin analogues is important
      for bioactivity, protein binding and tissue distribution may serve to protect
      UBS109 from full metabolism in vivo while allowing it to exert a pharmacological
      effect by means of slow drug release. 

PMID- 24900829
TI  - Analogues of the Natural Product Sinefungin as Inhibitors of EHMT1 and EHMT2.
AB  - A series of analogues of the natural product sinefungin lacking the amino acid
      moiety was synthesized and probed for their ability to inhibit EHMT1 and EHMT2.
      This study led to inhibitors 3b and 4d of methyltransferase activity of EHMT1 and
      EHMT2 and it demonstrates that such analogues constitute an interesting scaffold
      to develop selective methyltransferase inhibitors. Surprisingly, the inhibition
      was not competitive toward AdoMet. 

PMID- 24900830
TI  - Discovery and Biological Evaluation of Novel Dual EGFR/c-Met Inhibitors.
AB  - Activating mutations in the epidermal growth factor receptor (EGFR) have been
      identified in a subset of non-small cell lung cancer (NSCLC), which is one of the
      leading cancer types worldwide. Application of EGFR tyrosine kinase inhibitors
      leads to acquired resistance by secondary EGFR mutations or by amplification of
      the hepatocyte growth factor receptor (c-Met) gene. Although several EGFR and c
      Met inhibitors have been reported, potent dual EGFR/c-Met inhibitors, which can
      overcome this latter resistance mechanism, have hitherto not been published and
      have not reached clinical trials. In the present study we have identified dual
      EGFR/c-Met inhibitors and designed novel N-[4-(quinolin-4-yloxy)-phenyl]
      biarylsulfonamide derivatives, which inhibit the c-Met receptor and both the wild
      type and the activating mutant EGFR kinases in nanomolar range. We have
      demonstrated by Western blot analysis that compound 10 inhibits EGFR and c-Met
      phosphorylation at cellular level and effectively inhibits viability of the NSCLC
      cell lines. 

PMID- 24900831
TI  - Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK
      Multikinase Inhibitory Activities.
AB  - By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3
      benzazepine or benzazecine, into the classical RTK inhibitor 2,4
      diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues
      (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high
      potency against both c-Met and ALK kinases. Compound 8a displayed appreciable
      antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK
      xenograft mice model. 

PMID- 24900832
TI  - Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen
      Scanning.
AB  - Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an
      aromatic ring in our leads 11a and 13g by applying nitrogen scanning afforded a
      set of compounds that improved not only the solubility but also the metabolic
      stability. The impact after nitrogen substitution on interactions between a
      derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel)
      was also detected, most of them contributing to weaker interactions. After
      identifying the positions that kept inhibitory activity on HCT116 cell growth and
      Raf/MEK, compound 1 (CH5126766/RO5126766) was selected as a clinical compound. A
      phase I clinical trial is ongoing for solid cancers. 

PMID- 24900833
TI  - Discovery of Short Peptides Exhibiting High Potency against Cryptococcus
      neoformans.
AB  - Rapid increase in the emergence of resistance against existing antifungal drugs
      created a need to discover new structural classes of antifungal agents. In this
      study we describe the synthesis of a new structural class of short antifungal
      peptidomimetcis, their activity, and plausible mechanism of action. The results
      of the study show that peptides 11e and 11f are more potent than the control drug
      amphotericin B, with no cytotoxicity to human cancer cells and noncancerous
      mammalian kidney cells. The selectivity of peptides to fungus is depicted by
      transmission electron microscopy studies, and it revealed that 11e possibly
      disrupts the model membrane of the fungal pathogen. 

PMID- 24900834
TI  - Multicolor imaging of endoplasmic reticulum-located esterase as a prodrug
      activation enzyme.
AB  - The carboxylesterase families of enzymes are key participants in phase I drug
      metabolism processes. Carboxylesterase families 1 and 2 are of particular
      clinical relevance. These enzymes produce endoplasmic reticulum localization
      signals, are primarily localized in the endoplasmic reticulum, and hydrolyze a
      wide range of ester-containing prodrugs into an activated form. In order to
      detect enzymes belonging to both families, we developed an optical multicolor
      imaging technique, which provides a distinct color window for multicolor imaging.
      This technique required the design and synthesis of three new mechanistic colored
      probes that fluoresce red, green, or blue and are based on the quinone methide
      cleavage process. These activity-based probes allow rapid and clear visualization
      with high specificity against the endoplasmic reticulum in cultured cells based
      on endoplasmic reticulum localized esterases including both families of
      carboxylesterase enzymes. 

PMID- 24900835
TI  - Development of [(3)H]2-Carboxy-4,6-dichloro-1H-indole-3-propionic Acid ([(3)H]PSB
      12150): A Useful Tool for Studying GPR17.
AB  - The recently described synthetic GPR17 agonist 2-carboxy-4,6-dichloro-1H-indole-3
      propionic acid (1) was prepared in tritium-labeled form by catalytic
      hydrogenation of the corresponding propenoic acid derivative 8 with tritium gas.
      The radioligand [(3)H]PSB-12150 (9) was obtained with a specific activity of 17
      Ci/mmol (629 GBq/mmol). It showed specific and saturable binding to a single
      binding site in membrane preparations from Chinese hamster ovary cells
      recombinantly expressing the human GPR17. A competition assay procedure was
      established, which allows the determination of ligand binding affinities. 

PMID- 24900836
TI  - Design and Evaluation of omega-Hydroxy Fatty Acids Containing alpha-GalCer
      Analogues for CD1d-Mediated NKT Cell Activation.
AB  - CD1d molecules recognize glycolipid antigens with straight chain fatty acid
      moieties. Although most of the residues in the CD1d binding groove are
      hydrophobic, some of the amino acids can form hydrogen bonds. Consequently, we
      have designed omega-hydroxy fatty acid-containing glycolipid derivatives of the
      prototypical CD1d ligand alpha-GalCer. The potency of the omega-hydroxy analogues
      of the proper length is comparable to that of alpha-GalCer. We propose, based on
      the biological results and molecular modeling studies, that a hydrogen bonding
      interaction is involved between the omega-hydroxy group and a polar amino acid
      residue in the hydrophobic binding groove. 

PMID- 24900837
TI  - Iron chelators in photodynamic therapy revisited: synergistic effect by novel
      highly active thiosemicarbazones.
AB  - In photodynamic therapy (PDT), a noninvasive anticancer treatment, visible light,
      is used as a magic bullet selectively destroying cancer cells by a
      photosensitizer that is nontoxic in the dark. Protoporphyrin IX (PpIX) is a
      natural photosensitizer synthesized in the cell, which is also a chelating agent
      that if bonded to Fe(2+) forms heme, a central component of hemoglobin.
      Therefore, xenobiotic iron chelators can disturb iron homeostasis, increasing the
      accumulation of PpIX, obstructing the last step of heme biosynthesis, and
      enhancing PDT efficiency. However, the attempts to use this promising idea have
      not proved to be hugely successful. Herein, we revisited this issue by analyzing
      the application of iron chelators highly toxic in the dark, which should have
      higher Fe(2+) affinity than the nontoxic chelators used so far. We have designed
      and prepared thiosemicarbazones (TSC) with the highest dark cellular cytotoxicity
      among TSCs ever reported. We demonstrate that compound 2 exerts powerful PDT
      enhancement when used in combination with 5-aminolevulinic acid (ALA), a
      precursor of PpIX. 

PMID- 24900838
TI  - Delayed and Prolonged Histone Hyperacetylation with a Selective HDAC1/HDAC2
      Inhibitor.
AB  - The identification and in vitro and in vivo characterization of a potent SHI-1:2
      are described. Kinetic analysis indicated that biaryl inhibitors exhibit slow
      binding kinetics in isolated HDAC1 and HDAC2 preparations. Delayed histone
      hyperacetylation and gene expression changes were also observed in cell culture,
      and histone acetylation was observed in vivo beyond disappearance of drug from
      plasma. In vivo studies further demonstrated that continuous target inhibition
      was well tolerated and efficacious in tumor-bearing mice, leading to tumor growth
      inhibition with either once-daily or intermittent administration. 

PMID- 24900839
TI  - Interkingdom pharmacology of Angiotensin-I converting enzyme inhibitor
      phosphonates produced by actinomycetes.
AB  - The K-26 family of bacterial secondary metabolites are N-modified tripeptides
      terminated by an unusual phosphonate analog of tyrosine. These natural products,
      produced via three different actinomycetales, are potent inhibitors of human
      angiotensin-I converting enzyme (ACE). Herein we investigate the interkingdom
      pharmacology of the K-26 family by synthesizing these metabolites and assessing
      their potency as inhibitors of both the N-terminal and C-terminal domains of
      human ACE. In most cases, selectivity for the C-terminal domain of ACE is
      displayed. Co-crystallization of K-26 in both domains of human ACE reveals the
      structural basis of the potent inhibition and has shown an unusual binding motif
      that may guide future design of domain-selective inhibitors. Finally, the
      activity of K-26 is assayed against a cohort of microbially produced ACE
      relatives. In contrast to the synthetic ACE inhibitor captopril, which
      demonstrates broad interkingdom inhibition of ACE-like enzymes, K-26 selectively
      targets the eukaryotic family. 

PMID- 24900840
TI  - Enhancing a CH-pi Interaction to Increase the Affinity for 5-HT1A Receptors.
AB  - An electrostatic interaction related to a favorable position of the distal phenyl
      ring and a phenylalanine residue in the binding pocket would explain the higher 5
      HT1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to
      the corresponding 4-phenylpiperazine analogue. To explore a possible
      reinforcement of this interaction to increase the affinity for 5-HT1A receptors,
      different 4-substituted-phenyl analogues were synthesized and tested. The most
      important increase of affinity is obtained with two electron-donating methyl
      groups in positions 3 and 5. 

PMID- 24900841
TI  - Structure-Activity Relationship of Semicarbazone EGA Furnishes Photoaffinity
      Inhibitors of Anthrax Toxin Cellular Entry.
AB  - EGA, 1, prevents the entry of multiple viruses and bacterial toxins into
      mammalian cells by inhibiting vesicular trafficking. The cellular target of 1 is
      unknown, and a structure-activity relationship study was conducted in order to
      develop a strategy for target identification. A compound with midnanomolar
      potency was identified (2), and three photoaffinity labels were synthesized (3
      5). For this series, the expected photochemistry of the phenyl azide moiety is a
      more important factor than the IC50 of the photoprobe in obtaining a successful
      photolabeling event. While 3 was the most effective reversible inhibitor of the
      series, it provided no protection to cells against anthrax lethal toxin (LT)
      following UV irradiation. Conversely, 5, which possessed weak bioactivity in the
      standard assay, conferred robust irreversible protection vs LT to cells upon UV
      photolysis. 

PMID- 24900842
TI  - Novel delta opioid receptor agonists with oxazatricyclodecane structure.
AB  - We synthesized compounds 4a,c-f,h,i containing the oxazatricyclodecane structure
      from a novel rearrangement reaction product 2a. All the prepared compounds 4a,c
      f,h,i exhibited full agonistic activities for the delta opioid receptor (DOR).
      Among them, the N-methyl derivative 4c was highly selective, and the most
      effective DOR agonist in functional assays. Subcutaneous administration of 4c
      produced dose-dependent and NTI (selective DOR antagonist)-reversible
      antinociception lacking any convulsive behaviors in the mice acetic acid writhing
      tests. The N-methyl derivative 4c is expected to be a promising lead compound for
      selective DOR agonists with a novel chemotype. 

PMID- 24900843
TI  - Plasmepsin inhibitory activity and structure-guided optimization of a potent
      hydroxyethylamine-based antimalarial hit.
AB  - Antimalarial hit 1 SR (TCMDC-134674) identified in a GlaxoSmithKline cell based
      screening campaign was evaluated for inhibitory activity against the digestive
      vacuole plasmepsins (Plm I, II, and IV). It was found to be a potent Plm IV
      inhibitor with no selectivity over Cathepsin D. A cocrystal structure of 1 SR
      bound to Plm II was solved, providing structural insight for the design of more
      potent and selective analogues. Structure-guided optimization led to the
      identification of structurally simplified analogues 17 and 18 as low nanomolar
      inhibitors of both, plasmepsin Plm IV activity and P. falciparum growth in
      erythrocytes. 

PMID- 24900844
TI  - Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of
      EZH2.
AB  - The identification and development of a novel series of small molecule Enhancer
      of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular
      synthesis enabled the rapid development of structure-activity relationships,
      which led to the identification of 44 as a potent, SAM-competitive inhibitor of
      EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma
      cells. 

PMID- 24900845
TI  - Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists.
AB  - We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1).
      Herein, we describe our efforts in improving the drug-like properties of the full
      agonists through the systematic introduction of polar groups in the C-, D-, and A
      rings. This led to the discovery of new GPR40 full agonists with significantly
      improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo
      efficacy in oral glucose tolerance tests in mice in addition to the improvement
      in properties. 

PMID- 24900846
TI  - Vivid tumor imaging utilizing liposome-carried bimodal radiotracer.
AB  - By developing a new bimodal radioactive tracer that emits both luminescence and
      nuclear signals, a trimodal liposome for optical, nuclear, and magnetic resonance
      imaging is efficiently prepared. Fast clearance of the radiotracer from
      reticuloendothelial systems enables vivid tumor imaging with minimum background. 

PMID- 24900847
TI  - Digitoxin analogues with improved anticytomegalovirus activity.
AB  - Cardiac glycosides are potent inhibitors of cancer cell growth and possess
      antiviral activities at nanomolar concentrations. In this study we evaluated the
      anticytomegalovirus (CMV) activity of digitoxin and several of its analogues. We
      show that sugar type and sugar length attached to the steroid core structure
      affects its anticytomegalovirus activity. Structure-activity relationship (SAR)
      studies identified the l-sugar containing cardiac glycosides as having improved
      anti-CMV activity and may lead to better understanding of how these compounds
      inhibit CMV replication. 

PMID- 24900848
TI  - C-ring cannabinoid lactones: a novel cannabinergic chemotype.
AB  - As a part of our controlled-deactivation ligand development project, we recently
      disclosed a series of (-)-Delta(8)-tetrahydrocannabinols (THCs) with a
      metabolically labile ester group at the 2'-position of the side chain. Now, we
      have replaced the C-ring in the classical THC structure with a hydrolyzable seven
      membered lactone. One of the synthesized analogues binds with high affinity to
      the CB1 receptor (K i = 4.6 nM) and exhibits much lower affinities for the mCB2
      and the hCB2. Also, in vitro functional characterization found the compound to be
      an agonist at rCB1. Consistent with our rational design, the lead cannabinergic
      lactone identified here is susceptible to metabolic inactivation by plasma
      esterases, while the respective acid metabolite is inactive at CB receptors.
      These results are highlighted with molecular modeling of the two regiosomeric
      lactones. 

PMID- 24900849
TI  - Oxathiazolones Selectively Inhibit the Human Immunoproteasome over the
      Constitutive Proteasome.
AB  - Selective inhibitors for the human immunoproteasome LMP7 (beta5i) subunit over
      the constitutive proteasome hold promise for the treatment of autoimmune and
      inflammatory diseases and hematologic malignancies. Here we report that
      oxathiazolones inhibit the immunoproteasome beta5i with up to 4700-fold
      selectivity over the constitutive proteasome, are cell permeable, and inhibit
      proteasomes inside cells. 

PMID- 24900850
TI  - Minibody-indocyanine green based activatable optical imaging probes: the role of
      short polyethylene glycol linkers.
AB  - Minibodies show rapider blood clearance than IgGs due to smaller size that
      improves target-to-background ratio (TBR) in in vivo imaging. Additionally, the
      ability to activate an optical probe after binding to the target greatly improves
      the TBR. An optical imaging probe based on a minibody against prostate-specific
      membrane antigen (PSMA-MB) and conjugated with an activatable fluorophore,
      indocyanine green (ICG), was designed to fluoresce only after binding to cell
      surface PSMA. To further reduce background signal, short polyethylene glycol
      (PEG) linkers were employed to improve the covalent bonding ratio of ICG. New
      PSMA-MBs conjugated with bifunctional ICG derivatives specifically visualized
      PSMA-positive tumor xenografts in mice bearing both PSMA-positive and -negative
      tumors within 6 h postinjection. The addition of short PEG linkers significantly
      improved TBRs; however, it did not significantly alter the biodistribution. Thus,
      minibody-ICG conjugates could be a good alternative to IgG-ICG in the optical
      cancer imaging for further clinical applications. 

PMID- 24900853
TI  - 3-Amido-3-aryl-piperidines: A Novel Class of Potent, Selective, and Orally Active
      GlyT1 Inhibitors.
AB  - 3-Amido-3-aryl-piperidines were discovered as a novel structural class of GlyT1
      inhibitors. The structure-activity relationship, which was developed, led to the
      identification of highly potent compounds exhibiting excellent selectivity
      against the GlyT2 isoform, drug-like properties, and in vivo activity after oral
      administration. 

PMID- 24900851
TI  - Discovery of AZD3199, An Inhaled Ultralong Acting beta2 Receptor Agonist with
      Rapid Onset of Action.
AB  - A series of dibasic des-hydroxy beta2 receptor agonists has been prepared and
      evaluated for potential as inhaled ultralong acting bronchodilators.
      Determination of activities at the human beta-adrenoreceptors demonstrated a
      series of highly potent and selective beta2 receptor agonists that were
      progressed to further study in a guinea pig histamine-induced bronchoconstriction
      model. Following further assessment by onset studies in guinea pig tracheal rings
      and human bronchial rings contracted with methacholine (guinea pigs) or carbachol
      (humans), duration of action studies in guinea pigs after intratracheal (i.t.)
      administration and further selectivity and safety profiling AZD3199 was shown to
      have an excellent over all profile and was progressed into clinical evaluation as
      a new ultralong acting inhaled beta2 receptor agonist with rapid onset of action.

PMID- 24900852
TI  - Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.
AB  - An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was
      used to screen the Boehringer Ingelheim compound collection. Hit-to-lead and lead
      optimization beginning with compound 1 established the importance of the C3 and
      C4 substituent to antiviral potency against viruses with different aa124/aa125
      variants of IN. The importance of the C7 position on the serum shifted potency
      was established. Introduction of a quinoline substituent at the C4 position
      provided a balance of potency and metabolic stability. Combination of these
      findings ultimately led to the discovery of compound 26 (BI 224436), the first
      NCINI to advance into a phase Ia clinical trial. 

PMID- 24900854
TI  - R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior
      Efficacy Against Trypanosoma cruzi.
AB  - Sterol 14alpha-demethylase (CYP51) is an important therapeutic target for fungal
      and parasitic infections due to its key role in the biosynthesis of ergosterol,
      an essential component of the cell membranes of these pathogenic organisms. We
      report the development of potent and selective d-tryptophan-derived inhibitors of
      T. cruzi CYP51. Structural information obtained from the cocrystal structure of
      CYP51 and (R)-2, which is >1000-fold more potent than its enantiomer (S)-1, was
      used to guide design of additional analogues. The in vitro efficacy data
      presented here for (R)-2-(R)-8, together with preliminary in vitro
      pharmacokinetic data suggest that this new CYP51 inhibitor scaffold series has
      potential to deliver drug candidates for treatment of T. cruzi infections. 

PMID- 24900855
TI  - Creation of Novel Cores for beta-Secretase (BACE-1) Inhibitors: A Multiparameter
      Lead Generation Strategy.
AB  - In order to find optimal core structures as starting points for lead
      optimization, a multiparameter lead generation workflow was designed with the
      goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. De novo
      design of core fragments was connected with three predictive in silico models
      addressing target affinity, permeability, and hERG activity, in order to guide
      synthesis. Taking advantage of an additive SAR, the prioritized cores were
      decorated with a few, well-characterized substituents from known BACE-1
      inhibitors in order to allow for core-to-core comparisons. Prediction methods and
      analyses of how physicochemical properties of the core structures correlate to in
      vitro data are described. The syntheses and in vitro data of the test compounds
      are reported in a separate paper by Ginman et al. [J. Med. Chem. 2013, 56, 4181
      4205]. The affinity predictions are described in detail by Roos et al. [J. Chem.
      Inf. 2014, DOI: 10.1021/ci400374z]. 

PMID- 24900856
TI  - Trifluoromethyl fluorocoxib a detects cyclooxygenase-2 expression in inflammatory
      tissues and human tumor xenografts.
AB  - Fluorocoxib A is an effective COX-2-targeted optical imaging agent, used for in
      vivo detection of inflammatory tissues and premalignant and malignant tumors that
      express elevated levels of COX-2 (Uddin et al. Cancer Res. 2010, 70, 3618-3627).
      In an effort to discover novel optical probes for COX-2, a trifluoromethyl
      analogue of fluorocoxib A (CF3-fluorocoxib A) was synthesized and evaluated for
      its ability to inhibit COX-2 in vitro purified enzyme and human cancer cell
      lines. Kinetic analysis revealed that CF3-fluorocoxib A is a slow, tight binding
      inhibitor of COX-2 that exhibits low nanomolar inhibitory potency. While CF3
      fluorocoxib A and fluorocoxib A are similar in structure, CF3-fluorocoxib A shows
      improved potency in inhibition of wtCOX-2 and with a series of site-directed COX
      2 mutants. After intraperitoneal injection, selective uptake of CF3-fluorocoxib A
      is detected in inflamed mouse paws compared to noninflamed contralateral paws by
      optical imaging, and uptake is blocked by pretreatment with the COX-2 inhibitor,
      celecoxib. Selective uptake is also detected in the COX-2-positive human tumor
      xenografts (1483 HNSCC) as compared with the COX-2-negative tumor xenografts
      (HCT116) in an in vivo nude mouse tumor model. These in vitro and in vivo studies
      suggest that binding to COX-2 is the major determinant of uptake of CF3
      fluorocoxib A into the inflamed tissues and tumor xenografts. Thus, this new COX
      2-targeted imaging probe should find utility in the detection and evaluation of
      COX-2 status in naturally occurring malignancies. 

PMID- 24900858
TI  - Systems biology approach to developing "systems therapeutics".
AB  - The standard drug development model uses reductionist approaches to discover
      small molecules targeting one pathway. Although systems biology analyzes multiple
      pathways, the approach is often used to develop a small molecule interacting at
      only one pathway in the system. Similar to that in physics where a departure from
      the old reductionist "Copenhagen View" of quantum physics to a new and predictive
      systems based, collective model has emerged yielding new breakthroughs such as
      the LASER, a new model is emerging in biology where systems biology is used to
      develop a new technology acting at multiple pathways called "systems
      therapeutics." 

PMID- 24900859
TI  - Treatment of Immunological or Inflammatory Disorders with ITK Kinase Inhibitors.

PMID- 24900860
TI  - Pyrimidinylpiperdinyloxypyridone Analogues as GPR119 Modulators.

PMID- 24900861
TI  - Fused Thiazin-3-ones as KCa3.1 Inhibitors.

PMID- 24900862
TI  - Phenylalanine-Based Inactivator of AKT Kinase: Design, Synthesis, and Biological
      Evaluation.
AB  - Strategies to inhibit kinases by targeting the substrate binding site offer many
      advantages, including naturally evolved selectivity filters, but normally suffer
      from poor potency. In this work we propose a strategy to design and prepare
      covalent substrate-competitive kinase inhibitors as a method to improve potency.
      We have chosen AKT as the model kinase for this work. Using the AKT-GSK3beta
      cocrystal structure and a reactive cysteine near the substrate binding site, we
      have identified phenylalanine (Phe) as an appropriate scaffold for the covalent
      inactivator portion of these inhibitors. By synthesizing compounds that
      incorporate cysteine-reactive electrophiles into phenylalanine and testing these
      compounds as AKT inhibitors, we have identified Boc-Phe-vinyl ketone as a
      submicromolar inactivator of AKT. We also show that Boc-Phe-vinyl ketone (1)
      potently inhibits AKT1 and inhibits cell growth in HCT116 and H460 cells nearly
      as well as AKT inhibitors GSK690693 and MK-2206, (2) is selective for kinases
      that possess an activation loop cysteine such as AKT, (3) requires the vinyl
      ketone for inactivation, (4) has inactivation that is time-dependent, and (5)
      alkylates Cys310 of AKT as shown by mass spectrometry. Identification of Boc-Phe
      vinyl ketone as a covalent inactivator of AKT will allow the development of
      peptide and small-molecule substrate-competitive covalent kinase inhibitors that
      incorporate additional substrate binding elements to increase selectivity and
      potency. This proof-of-principle study also provides a basis to apply this
      strategy to other kinases of the AGC and CAMK families. 

PMID- 24900863
TI  - Synthesis and Biological Evaluation of New Quinoxaline Derivatives of ICF01012 as
      Melanoma-Targeting Probes.
AB  - The aim of this study was the synthesis and pharmacokinetic selection of a best
      melanin-targeting ligand for addressing anticancer agents to pigmented melanoma.
      Seven quinoxaline carboxamide derivatives were synthesized and radiolabeled with
      iodine-125. Biodistribution studies of compounds [ (125) I]1a-g performed in
      melanoma-bearing mice tumor showed significant tumor uptake (range 2.43
      5.68%ID/g) within 1 h after i.v. injection. Fast clearance of the radioactivity
      from the nontarget organs mainly via the urinary system gave high tumor-to-blood
      and tumor-to-muscle ratios. Given its favorable clearance and high tumor-melanoma
      uptake at 72 h, amide 1d was the most promising melanoma-targeting ligand in this
      series. Compound 1d will be used as building block for the design of new melanoma
      selective drug delivery systems. 

PMID- 24900865
TI  - Discovery of antitubulin agents with antiangiogenic activity as single entities
      with multitarget chemotherapy potential.
AB  - Antiangiogenic agents (AA) are cytostatic, and their utility in cancer
      chemotherapy lies in their combination with cytotoxic chemotherapeutic agents.
      Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2)
      inhibitors with antitubulin agents have been particularly successful. We have
      discovered a novel, potentially important analogue, that combines potent VEGFR2
      inhibitory activity (comparable to that of sunitinib) with potent antitubulin
      activity (comparable to that of combretastatin A-4 (CA)) in a single molecule,
      with GI50 values of 10(-7) M across the entire NCI 60 tumor cell panel. It
      potently inhibited tubulin assembly and circumvented the most clinically relevant
      tumor resistance mechanisms (P-glycoprotein and beta-III tubulin expression) to
      antimicrotubule agents. The compound is freely water-soluble as its HCl salt and
      afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib,
      or Temozolomide, without any toxicity. 

PMID- 24900864
TI  - Discovery of PF-5190457, a Potent, Selective, and Orally Bioavailable Ghrelin
      Receptor Inverse Agonist Clinical Candidate.
AB  - The identification of potent, highly selective orally bioavailable ghrelin
      receptor inverse agonists from a spiro-azetidino-piperidine series is described.
      Examples from this series have promising in vivo pharmacokinetics and increase
      glucose-stimulated insulin secretion in human whole and dispersed islets. A
      physicochemistry-based strategy to increase lipophilic efficiency for ghrelin
      receptor potency and retain low clearance and satisfactory permeability while
      reducing off-target pharmacology led to the discovery of 16h. Compound 16h has a
      superior balance of ghrelin receptor pharmacology and off-target selectivity. On
      the basis of its promising pharmacological and safety profile, 16h was advanced
      to human clinical trials. 

PMID- 24900866
TI  - Biological evaluation of subglutinol a as a novel immunosuppressive agent for
      inflammation intervention.
AB  - Subglutinol A (1) is an immunosuppressive natural product isolated from Fusarium
      subglutinans, an endophytic fungus from the vine Tripterygium wilfordii. We show
      that 1 exerts multimodal immune-suppressive effects on activated T cells in
      vitro: subglutinol A (1) effectively blocks T cell proliferation and survival
      while profoundly inhibiting pro-inflammatory IFNgamma and IL-17 production by
      fully differentiated effector Th1 and Th17 cells. Our data further reveal that 1
      may exert its anti-inflammatory effects by exacerbating mitochondrial damage in T
      cells. Additionally, we demonstrate that 1 significantly reduces lymphocytic
      infiltration into the footpad and ameliorates footpad swelling in the mouse model
      of Th1-driven delayed-type hypersensitivity. These results suggest the potential
      of 1 as a novel therapeutic for inflammatory diseases. 

PMID- 24900867
TI  - Biarylmethoxy Nicotinamides As Novel and Specific Inhibitors of Mycobacterium
      tuberculosis.
AB  - A whole cell based screening effort on a focused library from corporate
      collection resulted in the identification of biarylmethoxy nicotinamides as novel
      inhibitors of M. tuberculosis (Mtu) H37Rv. The series exhibited tangible
      structure-activity relationships, and during hit to lead exploration, a cellular
      potency of 100 nM was achieved, which is an improvement of >200-fold from the
      starting point. The series is very specific to Mtu and noncytotoxic up to 250 MUM
      as measured in the mammalian cell line THP-1 based cytotoxicity assay. This
      compound class retains its potency on several drug sensitive and single drug
      resistant clinical isolates, which indicate that the compounds could be acting
      through a novel mode of action. 

PMID- 24900868
TI  - Facile Synthesis and Preliminary Structure-Activity Analysis of New Sulfonamides
      Against Trypanosoma brucei.
AB  - The high throughput screening of a library of over 87,000 drug-like compounds
      against the African sleeping sickness parasite resulted in the discovery of hits
      with a wide range of molecular diversity. We report here the medicinal chemistry
      development of one such hit, a tetrahydroisoquinoline disulfonamide, with the
      synthesis and testing of 26 derivatives against the trypanosome subspecies.
      Activities in the 2-4 MUM range were revealed with a selectivity index suitable
      for further development. 

PMID- 24900869
TI  - Predicting the reactivity of nitrile-carrying compounds with cysteine: a combined
      computational and experimental study.
AB  - Here, we report on a mechanistic investigation based on DFT calculations and
      kinetic measures aimed at determining the energetics related to the cysteine
      nucleophilic attack on nitrile-carrying compounds. Activation energies were found
      to correlate well with experimental kinetic measures of reactivity with cysteine
      in phosphate buffer. The agreement between computations and experiments points to
      this DFT-based approach as a tool for predicting both nitrile reactivity toward
      cysteines and the toxicity of nitriles as electrophile agents. 

PMID- 24900871
TI  - 2-(2-Arylphenyl)benzoxazole As a Novel Anti-Inflammatory Scaffold: Synthesis and
      Biological Evaluation.
AB  - The 2-(2-arylphenyl)benzoxazole moiety has been found to be a new and selective
      ligand for the enzyme cyclooxygenase-2 (COX-2). The 2-(2-arylphenyl)benzoxazoles
      3a-m have been synthesized by Suzuki reaction of 2-(2-bromophenyl)benzoxazole.
      Further synthetic manipulation of 3f and 3i led to 3o and 3n, respectively. The
      compounds 3g, 3n, and 3o selectively inhibited COX-2 with selectivity index of 3n
      much better than that of the COX-2 selective NSAID celecoxib. The in vivo anti
      inflammatory potency of 3g and 3n is comparable to that of celecoxib and the
      nonselective NSAID diclofenac at two different doses, and 3o showed better
      potency compared to these clinically used NSAIDs. 

PMID- 24900870
TI  - Novel carboline derivatives as potent antifungal lead compounds: design,
      synthesis, and biological evaluation.
AB  - A series of novel antifungal carboline derivatives was designed and synthesized,
      which showed broad-spectrum antifungal activity. Particularly, compound C38
      showed comparable in vitro antifungal activity to fluconazole without toxicity to
      human embryonic lung cells. It also exhibited good fungicidal activity against
      both fluconazole-sensitive and -resistant Candida albicans cells and had potent
      inhibition activity against Candida albicans biofilm formation and hyphal growth.
      Moreover, C38 showed good synergistic antifungal activity in combination with
      fluconazole (FLC) against FLC-resistant Candida species. Preliminary mechanism
      studies revealed that C38 might act by inhibiting the synthesis of fungal cell
      wall. 

PMID- 24900872
TI  - Optimization of GPR40 Agonists for Type 2 Diabetes.
AB  - GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the
      treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin
      A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in
      type 2 diabetic patients in phase II clinical trials. We optimized
      phenylpropanoic acid derivatives as GPR40 agonists and identified AMG 837 (2) as
      a clinical candidate. Here we report our efforts in searching for structurally
      distinct back-ups for AMG 837. These efforts led to the identification of more
      polar GPR40 agonists, such as AM-4668 (10), that have improved potency, excellent
      pharmacokinetic properties across species, and minimum central nervous system
      (CNS) penetration. 

PMID- 24900873
TI  - Cryptocaryol Structure-Activity Relationship Study of Cancer Cell Cytotoxicity
      and Ability to Stabilize PDCD4.
AB  - The synthetic cryptocaryols A and B and a series of their analogues have been
      evaluated for their cytotoxicity and their ability to stabilize the tumor
      suppressor PDCD4. Cytotoxicities in the 3 to 30 MUM range were found. Both the
      cytotoxicity and PDCD4 stabilizing ability were tolerant of large stereochemical
      changes to the molecule. Co-dosing studies with cryptocaryols A and B and several
      known cancer drugs showed no measuable enhancement in cancer drug cytotoxicity. 

PMID- 24900874
TI  - New Hits as Antagonists of GPR103 Identified by HTS.
AB  - Preclinical data indicate that GPR103 receptor and its endogenous neuropeptides
      QRFP26 and QRFP43 are involved in appetite regulation. A high throughput
      screening (HTS) for small molecule GPR103 antagonists was performed with the
      clinical goal to target weight management by modulation of appetite. A high hit
      rate from the HTS and initial low confirmation with respect to functional versus
      affinity data challenged us to revise the established screening cascade. To
      secure high quality data while increasing throughput, the binding assay was
      optimized on quality to run at single concentration. This strategy enabled
      evaluation of a larger fraction of chemical clusters and singletons delivering 17
      new compound classes for GPR103 antagonism. Representative compounds from three
      clusters are presented. One of the identified clusters was further investigated,
      and an initial structure-activity relationship study is reported. The most potent
      compound identified had a pIC50 of 7.9 with an improved ligand lipophilic
      efficiency. 

PMID- 24900875
TI  - Dual RXR Agonists and RAR Antagonists Based on the Stilbene Retinoid Scaffold.
AB  - Arotinoids containing a C5,C8-diphenylnaphthalene-2-yl ring linked to a (C3
      halogenated) benzoic acid via an ethenyl connector (but not the corresponding
      naphthamides), which are prepared by Horner-Wadsworth-Emmons reaction of
      naphthaldehydes and benzylphosphonates, display the rather unusual property of
      being RXR agonists (15-fold induction of the RXR reporter cell line was achieved
      at 3- to 10-fold lower concentration than 9-cis-retinoic acid) and RAR
      antagonists as shown by transient transactivation studies. The binding of such
      bulky ligands suggests that the RXR ligand-binding domain is endowed with some
      degree of structural elasticity. 

PMID- 24900876
TI  - Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a
      Protein-Protein Interaction.
AB  - A class of novel oral fibrinolysis inhibitors has been discovered, which are
      lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As
      evidenced by X-ray crystallography the inhibitors bind to the lysine binding site
      in plasmin thus preventing plasmin from binding to fibrin, hence blocking the
      protein-protein interaction. Optimization of the series, focusing on potency in
      human buffer and plasma clotlysis assays, permeability, and GABAa selectivity,
      led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot
      lysis IC50 of 0.44 MUM, no detectable activity against GABAa, and with DMPK
      properties leading to a predicted dose of 340 mg twice a day oral dosing in
      humans. 

PMID- 24900877
TI  - Development of novel benzomorpholine class of diacylglycerol acyltransferase I
      inhibitors.
AB  - Diacylglycerol acyltransferase 1 (DGAT1) presents itself as a potential
      therapeutic target for obesity and diabetes for its important role in
      triglyceride biosynthesis. Herein we report the rational design of a novel class
      of DGAT1 inhibitors featuring a benzomorpholine core (23n). SAR exploration
      yielded compounds with good potency and selectivity as well as reasonable
      physical and pharmacokinetic properties. This class of DGAT1 inhibitors was
      tested in rodent models to evaluate DGAT1 inhibition as a novel approach for the
      treatment of metabolic diseases. Compound 23n conferred weight loss and a
      reduction in liver triglycerides when dosed chronically in mice with diet-induced
      obesity and depleted serum triglycerides following a lipid challenge. 

PMID- 24900878
TI  - Design, Synthesis, and Optimization of Balanced Dual NK1/NK3 Receptor
      Antagonists.
AB  - In connection with a program directed at potent and balanced dual NK1/NK3
      receptor ligands, a focused exploration of an original class of peptidomimetic
      derivatives was performed. The rational design and molecular hybridization of a
      novel phenylalanine core series was achieved to maximize the in vitro affinity
      and antagonism at both human NK1 and NK3 receptors. This study led to the
      identification of a new potent dual NK1/NK3 antagonist with pK i values of 8.6
      and 8.1, respectively. 

PMID- 24900880
TI  - Himbacine-derived thrombin receptor antagonists: c7-spirocyclic analogues of
      vorapaxar.
AB  - We have synthesized several C7-spirocyclic analogues of vorapaxar and evaluated
      their in vitro activities against PAR-1 receptor. Some of these analogues showed
      activities and rat plasma levels comparable to vorapaxar. Compound 5c from this
      series showed excellent PAR-1 activity (K i = 5.1 nM). We also present a model of
      these spirocyclic compounds docked to the PAR-1 receptor based on the X-ray
      crystal structure of vorapaxar bound to PAR-1 receptor. This model explains some
      of the structure-activity relationships in this series. 

PMID- 24900879
TI  - Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa.
AB  - It is urgent to develop novel anti-Pseudomonas agents that should also be active
      against multidrug resistant P. aeruginosa. Expanding the antibacterial spectrum
      of muraymycins toward P. aeruginosa was investigated by the systematic structure
      activity relationship study. It was revealed that two functional groups, a
      lipophilic side chain and a guanidino group, at the accessory moiety of
      muraymycins were important for the anti-Pseudomonas activity, and analogue 29
      exhibited antibacterial activity against a range of P. aeruginosa strains with
      the minimum inhibitory concentration values of 4-8 MUg/mL. 

PMID- 24900881
TI  - Kinesin spindle protein inhibitors with diaryl amine scaffolds: crystal packing
      analysis for improved aqueous solubility.
AB  - Diaryl amine derivatives have been designed and synthesized as novel kinesin
      spindle protein (KSP) inhibitors based on planar carbazole-type KSP inhibitors
      with poor aqueous solubility. The new generation of inhibitors was found to show
      comparable inhibitory activity and high selectivity for KSP, and this was
      accompanied with improved solubility. Kinetic analysis and molecular modeling
      studies suggested that these inhibitors work in an ATP-competitive manner via
      binding to the secondary allosteric site formed by alpha4 and alpha6 helices of
      KSP. Comparative structural investigations on a series of compounds revealed that
      the higher solubility of diaryl amine-type inhibitors was attributed to fewer van
      der Waals interactions in the crystal packing and the hydrogen-bond acceptor
      nitrogen of the aniline moiety for favorable solvation. 

PMID- 24900882
TI  - Pivotal Role of an Aliphatic Side Chain in the Development of an HDM2 Inhibitor.
AB  - Introduction of an aliphatic side chain to a key position of a novel piperidine
      based HDM2 inhibitor scaffold resulted in significant potency gains, enabling
      further series progression. 

PMID- 24900883
TI  - Chlorpheniramine Analogues Reverse Chloroquine Resistance in Plasmodium
      falciparum by Inhibiting PfCRT.
AB  - The emergence and spread of malaria parasites that are resistant to chloroquine
      (CQ) has been a disaster for world health. The antihistamine chlorpheniramine
      (CP) partially resensitizes CQ-resistant (CQR) parasites to CQ but possesses
      little intrinsic antiplasmodial activity. Mutations in the parasite's CQ
      resistance transporter (PfCRT) confer resistance to CQ by enabling the protein to
      transport the drug away from its site of action, and it is thought that
      resistance-reversers such as CP exert their effect by blocking this CQ transport
      activity. Here, a series of new structural analogues and homologues of CP have
      been synthesized. We show that these compounds (along with other in vitro CQ
      resistance-reversers) inhibit the transport of CQ via a resistance-conferring
      form of PfCRT expressed in Xenopus laevis oocytes. Furthermore, the level of
      PfCRT-inhibition was found to correlate well with both the restoration of CQ
      accumulation and the level of CQ resensitization in CQR parasites. 

PMID- 24900884
TI  - Late-Stage C-H Coupling Enables Rapid Identification of HDAC Inhibitors:
      Synthesis and Evaluation of NCH-31 Analogues.
AB  - We previously reported the discovery of NCH-31, a potent histone deacetylase
      (HDAC) inhibitor. By utilizing our C-H coupling reaction, we rapidly synthesized
      16 analogues (IYS-1 through IYS-15 and IYS-Me) of NCH-31 with different aryl
      groups at the C4-position of 2-aminothiazole core of NCH-31. Subsequent
      biological testing of these derivatives revealed that 3-fluorophenyl (IYS-10) and
      4-fluorophenyl (IYS-15) derivatives act as potent pan-HDAC inhibitor.
      Additionally, 4-methylphenyl (IYS-1) and 3-fluoro-4-methylphenyl (IYS-14)
      derivatives acted as HDAC6-insensitive inhibitors. The present work clearly shows
      the power of the late-stage C-H coupling approach to rapidly identify novel and
      highly active/selective biofunctional molecules. 

PMID- 24900885
TI  - Design and Syntheses of Anti-Tuberculosis Agents Inspired by BTZ043 Using a
      Scaffold Simplification Strategy.
AB  - Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), is a
      global public health concern because of the emergence of various resistant
      strains. Benzothiazin-4-ones (BTZs), represented by BTZ043, are a promising new
      class of agents for the treatment of tuberculosis and have been shown to kill Mtb
      in vitro, ex vivo, and in mouse models of TB. Herein we report the design and
      syntheses of nitroaromatic sulfonamide, reverse-amide, and ester classes of anti
      TB agents using a scaffold simplification strategy based on BTZ043. The presented
      work explores the effect of functional groups such as sulfonamides, reverse
      amides, and esters that are attached to the nitroaromatic rings on their anti-TB
      activity. The in vitro activity of the compounds evaluated against the H37Rv
      strain of Mtb show that nitroaromatic sulfonamides and nitrobenzoic acid esters
      with two nitro substituents were most active and highlights the importance of the
      electronic character (electron deficient aromatic ring) of the nitroaromatic ring
      as a central theme in these types of nitroaromatic anti-TB agents. 

PMID- 24900886
TI  - Discovery of a New Series of Naphthamides as Potent VEGFR-2 Kinase Inhibitors.
AB  - Inhibition of VEGFR-2 signaling pathway has already become one of the most
      promising approaches for the treatment of cancer. In this study, we describe the
      design, synthesis, and biological evaluation of a new series of naphthamides as
      potent inhibitors of VEGFR-2. Among these compounds, 14c exhibited high VEGFR-2
      inhibitory potency in both enzymatic and HUVEC cellular proliferation assays,
      with IC50 values of 1.5 and 0.9 nM, respectively. Kinase selectivity profiling
      revealed that 14c was a multitargeted inhibitor, and it also exhibited good
      potency against VEGFR-1, PDGFR-beta, and RET. Furthermore, 14c effectively
      blocked tube formation of HUVEC at nanomolar level. Overall, 14c might be a
      promising candidate for the treatment of cancer. 

PMID- 24900887
TI  - High content screening of diverse compound libraries identifies potent modulators
      of tubulin dynamics.
AB  - Tubulin modulating agents such as the taxanes are among the most effective
      antimitotic cancer drugs, although resistance and toxicity present significant
      problems in their clinical use. However, most tubulin modulators are derived from
      complex natural products, which can make modification of their structure to
      address these problems difficult. Here, we report the discovery of new
      antimitotic compounds with simple structures that can be rapidly synthesized,
      through the phenotypic screening of a diverse compound library for the induction
      of mitotic arrest. We first identified a compound, which induced mitotic arrest
      in human cells at submicromolar concentrations. Its simple structure enabled
      rapid exploration of activity, defining a biphenylacetamide moiety required for
      activity, A family of analogues was synthesized, yielding optimized compounds
      that caused mitotic arrest and cell death in the low nanomolar range, comparable
      to clinically used antimitotic agents. These compounds can be synthesized in 1-3
      steps and good yields. We show that one such compound targets tubulin, partially
      inhibiting colchicine but not vinblastine binding, suggesting that it acts
      allosterically to the known colchicine-binding site. Thus, our results exemplify
      the use of phenotypic screening to identify novel antimitotic compounds from
      diverse chemical libraries and characterize a family of biphenylacetamides
      (biphenabulins) that show promise for further development. 

PMID- 24900888
TI  - Discovery of naphthyl-fused 5-membered lactams as a new class of m1 positive
      allosteric modulators.
AB  - Selective activation of the M1 muscarinic receptor via positive allosteric
      modulation represents an original approach to treat the cognitive decline in
      patients with Alzheimer's disease. A series of naphthyl-fused 5-membered lactams
      were identified as a new class of M1 positive allosteric modulators and were
      found to possess good potency and in vivo efficacy. 

PMID- 24900889
TI  - Oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad
      spectrum antibacterial agents.
AB  - Bacterial resistance is eroding the clinical utility of existing antibiotics
      necessitating the discovery of new agents. Bacterial type II topoisomerase is a
      clinically validated, highly effective, and proven drug target. This target is
      amenable to inhibition by diverse classes of inhibitors with alternative and
      distinct binding sites to quinolone antibiotics, thus enabling the development of
      agents that lack cross-resistance to quinolones. Described here are novel
      bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and
      topo IV inhibitors and consist of three distinct structural moieties. The
      substitution of the linker moiety led to discovery of potent broad-spectrum NBTIs
      with reduced off-target activity (hERG IC50 > 18 MUM) and improved physical
      properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and
      Staphylococcus aureus gyrase (IC50 = 1.02 MUM) and topo IV (IC50 = 10.4 MUM).
      AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in
      a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S.
      aureus DNA-gyrase showed binding interactions similar to that reported for
      GSK299423, displaying a key contact of Asp83 with the basic amine at position-7
      of the linker. 

PMID- 24900890
TI  - Overcoming the translational roadblocks: a cancer care and research model.
AB  - There are many challenges to the process of translating the knowledge gained in
      the laboratory into new clinical approaches that can meet the needs of patients,
      clinicians and the wider community. We describe here an initiative that has
      borrowed concepts and principles from participatory research to produce a new
      process embedded in a cancer center aiming to facilitate translational research
      and overcome the three translational roadblocks. The centre-wide project named
      Personal Response Determinants in Cancer Therapy (PREDICT) operates with the
      support of the centre's leadership, staff, volunteers and patients to contribute
      to current and future cancer research successes. We describe the different phases
      of the project, the current structure and lessons learned during its evolution,
      highlighting how PREDICT contributes to translational research and its linkage to
      participatory research concepts. Despite the contextualized nature of the PREDICT
      initiative, we believe that the framework developed for the project has the
      potential to help other clinical centers to overcome the translational research
      roadblocks. 

PMID- 24900891
TI  - Biomechanics of hyperflexion and kneeling before and after total knee
      arthroplasty.
AB  - The capacity to perform certain activities is frequently compromised after total
      knee arthroplasty (TKA) due to a functional decline resulting from decreased
      range of motion and a diminished ability to kneel. In this manuscript, the
      current biomechanical understanding of hyperflexion and kneeling before and after
      TKA will be discussed. Patellofemoral and tibiofemoral joint contact area,
      contact pressure, and kinematics were evaluated in cadaveric studies using a
      Tekscan pressure measuring system and Microscribe. Testing was performed on
      intact knees and following cruciate retaining and posterior stabilized TKA at
      knee flexion angles of 90 degrees , 105 degrees , 120 degrees , and 135 degrees .
      Three loading conditions were used to simulate squatting, double stance kneeling,
      and single stance kneeling. Following TKA with double stance kneeling,
      patellofemoral contact areas did not increase significantly at high knee flexion
      angle (135 degrees ). Kneeling resulted in tibial posterior translation and
      external rotation at all flexion angles. Moving from double to single stance
      kneeling tended to increase pressures in the cruciate retaining group, but
      decreased pressures in the posterior stabilized group. The cruciate retaining
      group had significantly larger contact areas than the posterior stabilized group,
      although no significant differences in pressures were observed comparing the two
      TKA designs (p < 0.05). If greater than 120 degrees  of postoperative knee range
      of motion can be achieved following TKA, then kneeling may be performed with less
      risk in the patellofemoral joint than was previously believed to be the case.
      However, kneeling may increase the likelihood of damage to cartilage and menisci
      in intact knees and after TKA increases in tibiofemoral contact area and
      pressures may lead to polyethyelene wear if performed on a chronic, repetitive
      basis.

PMID- 24900892
TI  - Curved periacetabular osteotomy for the treatment of dysplastic hips.
AB  - Curved periacetabular osteotomy (CPO) was developed for the treatment of
      dysplastic hips in 1995. In CPO, the exposure of osteotomy sites and osteotomy of
      the ischium are made in the same manner as Bernese periacetabular osteotomy, and
      iliac and pubic osteotomies are performed in the same manner as rotational
      acetabular osteotomy. We studied the dynamic instabilities of 25 dysplastic hips
      before and after CPO using triaxial accelerometry. Overall magnitude of
      acceleration was significantly decreased from 2.30 +/- 0.57 m/sec(2)
      preoperatively to 1.55 +/- 0.31 m/sec(2) postoperatively. Pain relief and
      improvement of acetabular coverage resulting from acetabular reorientation seem
      to be related with reduction of dynamic instabilities of dysplastic hips.
      Isokinetic muscle strengths of 24 hips in 22 patients were measured
      preoperatively and after CPO. At 12 months postoperatively, the mean muscle
      strength exceeded the preoperative values. These results seem to be obtained due
      to no dissection of abductor muscles in CPO. The preoperative presence of
      acetabular cysts did not influence the results of CPO. An adequate rotation of
      the acetabular fragment induced cyst remodeling. Satisfactory results were
      obtained clinically and radiographically after CPO in patients aged 50 years or
      older. CPO alone for the treatment of severe dysplastic hips classified as
      subluxated hips of Severin group IV-b with preoperative CE angles of up to -20
      degrees  could restore the acetabular coverage, weight-bearing area and
      medialization of the hip joint. CPO without any other combined procedure, as a
      treatment for 17 hips in 16 patients with Perthes-like deformities, produced good
      mid-term clinical and radiographic results. We have been performing CPO in
      conjunction with osteochondroplasty for the treatment of acatabular dysplasia
      associated with femoroacetabular impingement since 2006. The combined procedure
      has been providing effective correction of both acetabular dysplasia and
      associated femoral head-neck deformities without any increased complication rate.
      We have encountered an obturator artery injury in one case and two intraoperative
      comminuted fractures. Although serious complications such as motor nerve palsy,
      deep infection, necrosis of the femoral head or acetabulum, and delayed union or
      nonunion of the ilium were reported, such complications have never occurred in
      our 700 cases so far.

PMID- 24900893
TI  - Treatment results of a periprosthetic femoral fracture case series: treatment
      method for Vancouver type b2 fractures can be customized.
AB  - BACKGROUND: Currently, an algorithmic approach for deciding treatment options
      according to the Vancouver classification is widely used for treatment of
      periprosthetic femoral fractures after hip arthroplasty. However, this treatment
      algorithm based on the Vancouver classification lacks consideration of patient
      physiology and surgeon's experience (judgment), which are also important for
      deciding treatment options. The purpose of this study was to assess the treatment
      results and discuss the treatment options using a case series. METHODS: Eighteen
      consecutive cases with periprosthetic femoral fractures after total hip
      arthroplasty and hemiarthroplasty were retrospectively reviewed. A locking
      compression plate system was used for osteosynthesis during the study period. The
      fracture type was determined by the Vancouver classification. The treatment
      algorithm based on the Vancouver classification was generally applied, but was
      modified in some cases according to the surgeon's judgment. The reasons for
      modification of the treatment algorithm were investigated. Mobility status,
      ambulatory status, and social status were assessed before the fracture and at the
      latest follow-up. Radiological results including bony union and stem stability
      were also evaluated. RESULTS: Thirteen cases were treated by osteosynthesis, two
      by revision arthroplasty and three by conservative treatment. Four cases of type
      B2 fractures with a loose stem, in which revision arthroplasty is recommended
      according to the Vancouver classification, were treated by other options. Of
      these, three were treated by osteosynthesis and one was treated conservatively.
      The reasons why the three cases were treated by osteosynthesis were technical
      difficulty associated with performance of revision arthroplasty owing to severe
      central migration of an Austin-Moore implant in one case and subsequent severe
      hip contracture and low activity in two cases. The reasons for the conservative
      treatment in the remaining case were low activity, low-grade pain, previous
      wiring around the fracture and light weight. All patients obtained primary bony
      union and almost fully regained their prior activities. CONCLUSIONS: We suggest
      reaching a decision regarding treatment methods of periprosthetic femoral
      fractures by following the algorithmic approach of the Vancouver classification
      in addition to the assessment of each patient's hip joint pathology, physical
      status and activity, especially for type B2 fractures. The customized treatments
      demonstrated favorable overall results.

PMID- 24900894
TI  - Complications and outcomes of minimally invasive percutaneous plating for
      proximal humeral fractures.
AB  - BACKGROUND: The minimally invasive plate osteosynthesis (MIPO) technique using
      periarticular locking plates may be a good option for the repair of displaced
      proximal humeral fractures. However, axillary nerve complications related to this
      technique may be underestimated. The purpose of this study is to evaluate the
      outcomes of the minimally invasive plating, focusing on the complications.
      METHODS: The records of 21 consecutive patients treated for proximal humerus
      fractures using the MIPO technique with locking plates were retrospectively
      reviewed. These patients were treated between March 2009 and March 2011 with a
      minimum one-year follow-up. The clinical function, complications, and
      radiological bony union were evaluated. RESULTS: All of the patients, with one
      exception, showed at least 90 degrees of flexion and abduction at the shoulder
      joint six months postoperatively. The average Constant scores at three months,
      six months, and one year follow-ups were 74.0 (range, 62 to 90), 79.4 (range, 64
      to 91), and 82.7 (range, 66 to 92), respectively. All of the patients achieved
      bony union within the average of 3.2 months (range, 2 to 6 months). There was one
      case of delayed union, one case of intra-articular screw penetration, and one
      case of axillary nerve paresis (incomplete injury), which did not completely
      recover during the one year of follow-up. CONCLUSIONS: The MIPO technique using
      periarticular locking plates is a useful option for the treatment of selected
      cases of displaced proximal humeral fractures. However, nerve complications such
      as axillary nerve paresis should be considered along with implant-related
      complications when choosing patients for minimally invasive plating.

PMID- 24900895
TI  - Accurate leg length measurement in total hip arthroplasty: a comparison of
      computer navigation and a simple manual measurement device.
AB  - BACKGROUND: Several studies have shown that better placement of the acetabular
      cup and femoral stem can be achieved in total hip arthroplasty (THA) by using the
      computer navigation system rather than the free-hand alignment methods. However,
      there have been no comparisons of the relevant clinical advantages in using the
      computer navigation as opposed to the manual intraoperative measurement devices.
      The purpose of this study is to determine whether the use of computer navigation
      can improve postoperative leg length discrepancy (LLD) compared to the use of the
      measurement device. METHODS: We performed a retrospective study comparing 30
      computer-assisted THAs with 40 THAs performed using a simple manual measurement
      device. RESULTS: The postoperative LLD was 3.0 mm (range, 0 to 8 mm) in the
      computer-assisted group and 2.9 mm (range, 0 to 10 mm) in the device group.
      Statistically significant difference was not seen between the two groups.
      CONCLUSIONS: The results showed good equalization of the leg lengths using both
      computed tomography-based navigation and the simple manual measurement device.

PMID- 24900896
TI  - Patient satisfaction after arthroscopic repair of acetabular labral tears.
AB  - BACKGROUND: Acetabular labral tear is a main cause of hip pain and disability,
      often requiring surgical treatment. Improvements of hip arthroscopic technique
      have produced positive outcomes after labral repair with arthroscopy. The purpose
      of this study was to determine clinical outcomes and patient satisfaction after
      arthroscopic repair of acetabular labral tear. METHODS: We interviewed 21
      patients (10 men and 11 women; mean age, 36 years [range, 22 to 57 years]) with
      acetabular labral tears that had been repaired arthroscopically in terms of
      satisfaction of the procedure. In addition, clinical outcome was assessed using
      visual analog scale (VAS) score, University of California, Los Angeles (UCLA)
      activity, Western Ontario and McMaster Universities (WOMAC) osteoarthritis index,
      and Harris hip score, and radiologic outcome was assessed using serial
      radiography. The patients were followed for 24-50 months. RESULTS: The mean
      Harris hip score was 73 points (range, 64 to 84 points) preoperatively and 83
      points (range, 66 to 95 points) postoperatively. Fifteen hips (71%) were rated
      excellent and good. The mean WOMAC osteoarthritis index and VAS scores were
      improved at final follow-up. UCLA activity at the latest follow-up improved in 16
      patients. The Tonnis grade of osteoarthritis at the latest follow-up did not
      change in all patients. Eighteen of the patients (86%) were satisfied with the
      procedure. CONCLUSIONS: High rate of satisfaction after arthroscopic repair of
      acetabular labral tears is an encouraging outcome. Arthroscopic treatment of
      labral tears might be a useful technique in patients with hip pathologies, such
      as femoroacetabular impingement with labral tears.

PMID- 24900897
TI  - Results of revision surgery and causes of unstable total knee arthroplasty.
AB  - BACKGROUND: The aim of this study was to evaluate causes of unstable total knee
      arthroplasty and results of revision surgery. METHODS: We retrospectively
      reviewed 24 knees that underwent a revision arthroplasty for unstable total knee
      arthroplasty. The average follow-up period was 33.8 months. We classified the
      instability and analyzed the treatment results according to its cause. Stress
      radiographs, postoperative component position, and joint level were measured.
      Clinical outcomes were assessed using the Hospital for Special Surgery (HSS)
      score and range of motion. RESULTS: Causes of instability included coronal
      instability with posteromedial polyethylene wear and lateral laxity in 13 knees,
      coronal instability with posteromedial polyethylene wear in 6 knees and coronal
      and sagittal instability in 3 knees including post breakage in 1 knee, global
      instability in 1 knee and flexion instability in 1 knee. Mean
      preoperative/postoperative varus and valgus angles were 5.8 degrees /3.2 degrees 
      (p = 0.713) and 22.5 degrees /5.6 degrees  (p = 0.032). Mean postoperative alpha,
      beta, gamma, delta angle were 5.34 degrees , 89.65 degrees , 2.74 degrees , 6.77
      degrees . Mean changes of joint levels were from 14.1 mm to 13.6 mm from fibular
      head (p = 0.82). The mean HSS score improved from 53.4 to 89.2 (p = 0.04). The
      average range of motion was changed from 123 degrees  to 122 degrees  (p = 0.82).
      CONCLUSIONS: Revision total knee arthroplasty with or without a more constrained
      prosthesis will be a definite solution for an unstable total knee arthroplasty.
      The solution according to cause is very important and seems to be helpful to
      avoid unnecessary over-constrained implant selection in revision surgery for
      total knee instability.

PMID- 24900898
TI  - A comparison of the fixation strengths provided by different intraosseous tendon
      lengths during anterior cruciate ligament reconstruction: a biomechanical study
      in a porcine tibial model.
AB  - BACKGROUND: The purpose of this study was to determine the tibial fixation
      strength provided by different intraosseous soft tissue graft lengths within the
      tibial tunnel. METHODS: Porcine tibial bones and digital flexor tendons were used
      for testing. Bone mineral densities of proximal tibial medial condyles were
      measured, and two-strand tendon bundles of 8 mm diameter were used. An
      intraosseous graft length of 2 cm was used in group 1 (n = 10), and a graft
      length of 4 cm was used in group 2 (n = 10). Tunnels were 4 cm in length and 8 mm
      in diameter. Tibial fixation was performed using a suture tied around a screw
      post with a washer and an additionally inserted 7 * 20 mm bioabsorbable screw.
      After applying preconditioning loading of 10 cycles, 1,000 cycles between 70-220
      N were applied at a frequency of 1 Hz. Graft slippage and total graft movement
      were recorded. Ultimate tensile strength was measured by pull-out testing at an
      Instron crosshead speed of 1,000 mm/min. RESULTS: No significant intergroup
      difference was found for total graft movement after cyclic loading (slippage in
      group 1, 1.2 mm and group 2, 1.2 mm, respectively, p = 0.917; and total graft
      movement in group 1, 3.3 mm and group 2, 2.7 mm, respectively, p = 0.199).
      However, mean ultimate tensile strength in group 2 was significantly higher than
      that in group 1 (group 1, 649.9 N; group 2, 938 N; p = 0.008). CONCLUSIONS: In a
      porcine model, ultimate tensile strength was greater for a 4 cm long intraosseous
      flexor tendon in the tibial tunnel. However, no intergroup difference in graft
      slippage or total graft movement was observed. The results show that a 2 cm
      intraosseous graft length in the tibial tunnel is safe and has sufficient
      strength (> 450 N) for adequate rehabilitation after anterior cruciate ligament
      reconstruction.

PMID- 24900899
TI  - Evaluation of bone mineral status in adolescent idiopathic scoliosis.
AB  - BACKGROUND: Several reports have suggested low bone mineral density (BMD) in
      patients with adolescent idiopathic scoliosis (AIS). We determined bone mineral
      status in patients with AIS to evaluate the effect of brace treatment on BMD.
      METHODS: BMD was measured in 46 patients (mean age, 17.8 +/- 4.9 years) with AIS
      (17 with brace and 29 without brace) by dual-energy X-ray absorptiometry scan and
      compared the results to an age-matched (mean age, 16.6 +/- 3.9 years) control
      group (n = 54). RESULTS: The AIS group had significantly lower bone mass at the
      lumbar spine (Z-score, -1.500 vs. -0.832) and hip (Z-score, -1.221 vs. -0.754)
      except at the femoral neck. No difference in BMD was found between patients with
      AIS who used a brace and those who did not. CONCLUSIONS: The results confirmed
      that BMD was low in AIS patients and it was not affected by brace treatment.

PMID- 24900900
TI  - Comparison of functional outcomes following surgical decompression and
      posterolateral instrumented fusion in single level low grade lumbar degenerative
      versus isthmic spondylolisthesis.
AB  - BACKGROUND: The two most common types of surgically treated lumbar
      spondylolisthesis in adults include the degenerative and isthmic types. The aim
      of this study was to compare the functional outcomes of surgical decompression
      and posterolateral instrumented fusion in patients with lumbar degenerative and
      isthmic spondylolisthesis. METHODS: In this retrospective study, we reviewed the
      clinical outcomes in surgically treated patients with single level, low grade
      lumbar degenerative, and isthmic spondylolisthesis (groups A and B, respectively)
      from August 2007 to April 2011. We tried to compare paired settings with similar
      initial conditions. Group A included 52 patients with a mean age of 49.2 +/- 6.1
      years, and group B included 52 patients with a mean age of 47.3 +/- 7.4 years.
      Minimum follow-up was 24 months. The surgical procedure comprised neural
      decompression and posterolateral instrumented fusion. Pain and disability were
      assessed by a visual analog scale (VAS) and the Oswestry Disability Index (ODI),
      respectively. The Wilcoxon and Mann-Whitney U-tests were used to compare indices.
      RESULTS: The most common sites for degenerative and isthmic spondylolisthesis
      were at the L4-L5 (88.5%) and L5-S1 (84.6%) levels, respectively. Surgery in both
      groups significantly improved VAS and ODI scores. The efficacy of surgery based
      on subjective satisfaction rate and pain and disability improvement was similar
      in the degenerative and isthmic groups. Notable complications were also
      comparable in both groups. CONCLUSIONS: Neural decompression and posterolateral
      instrumented fusion significantly improved pain and disability in patients with
      degenerative and isthmic spondylolisthesis. The efficacy of surgery for overall
      subjective satisfaction rate and pain and disability improvement was similar in
      both groups.

PMID- 24900901
TI  - Does well maintained graft provide consistent return to play after medial ulnar
      collateral ligament reconstruction of the elbow joint in elite baseball players?
AB  - BACKGROUND: Several studies have reported the clinical outcomes of medial ulnar
      collateral ligament (MUCL) reconstruction of the elbow joint in throwing
      athletes, including the rate of return to sports. However, little has been known
      about the imaging outcomes after MUCL reconstruction. The aim of this study is to
      report the clinical and imaging outcomes after MUCL reconstruction using figure
      of eight fashion in the elite and professional baseball players. METHODS: This
      study included 17 baseball players, who underwent MUCL reconstruction between
      July 2007 and May 2010. The average follow-up period was 48.6 months. Imaging
      assessment consisted of preoperative plain and stress radiographs, magnetic
      resonance imaging, and postoperative serial ultrasonography. The clinical
      assessments were composed of visual analogue scale (VAS) for pain, range of
      motion, and the Conway scale. RESULTS: The mean VAS score was 6.4 (range, 3 to 8)
      preoperatively and 2.2 (range, 0 to 4) postoperatively (p < 0.05). There were
      nine players (53%) classified as excellent who returned to sports at the same or
      higher level compared to preinjury. Serial ultrasonography revealed well
      maintained grafts at 3 and 12 months in all of the players. Five out of 17
      players showed decreased echogenecity in the common flexor tendon at 3 months,
      which was considered as remaining tissue swelling and resolved completely at 12
      months. CONCLUSIONS: All grafts are well-maintained until 12-months based on the
      ultrasonographic findings, although only 53% of the players returned to preinjury
      level.

PMID- 24900902
TI  - The incidence of acute traumatic tendon injuries in the hand and wrist: a 10-year
      population-based study.
AB  - BACKGROUND: Acute traumatic tendon injuries of the hand and wrist are commonly
      encountered in the emergency department. Despite the frequency, few studies have
      examined the true incidence of acute traumatic tendon injuries in the hand and
      wrist or compared the incidences of both extensor and flexor tendon injuries.
      METHODS: We performed a retrospective population-based cohort study of all acute
      traumatic tendon injuries of the hand and wrist in a mixed urban and rural
      Midwest county in the United States between 2001-2010. A regional epidemiologic
      database and medical codes were used to identify index cases. Epidemiologic
      information including occupation, year of injury, mechanism of injury and the
      injured tendon and zone were recorded. RESULTS: During the 10-year study period
      there was an incidence rate of 33.2 injuries per 100,000 person-years. There was
      a decreasing rate of injury during the study period. Highest incidence of injury
      occurred at 20-29 years of age. There was significant association between injury
      rate and age, and males had a higher incidence than females. The majority of
      cases involved a single tendon, with extensor tendon injuries occurring more
      frequently than flexor tendons. Typically, extensor tendon injuries involved zone
      three of the index finger, while flexor tendons involved zone two of the index
      finger. Work-related injuries accounted for 24.9% of acute traumatic tendon
      injuries. The occupations of work-related injuries were assigned to major groups
      defined by the 2010 Standard Occupational Classification structure. After
      assigning these patients' occupations to respective major groups, the most common
      groups work-related injuries occurred in construction and extraction occupations
      (44.2%), food preparation and serving related occupations (14.4%), and
      transportation and material moving occupations (12.5%). CONCLUSIONS: Epidemiology
      data enhances our knowledge of injury patterns and may play a role in the
      prevention and treatment of future injuries, with an end result of reducing lost
      work time and economic burden.

PMID- 24900903
TI  - Responsiveness of the Korean version of the Michigan Hand Outcomes Questionnaire
      after carpal tunnel release.
AB  - BACKGROUND: The Korean version of the Michigan Hand Outcomes Questionnaire (K
      MHQ) was recently validated; however, the questionnaire's responsiveness as well
      as the degree to which the instrument is sensitive to change has not been
      thoroughly evaluated in a specific condition in Koreans. We evaluated the
      responsiveness of the K-MHQ in a homogenous cohort of patients with carpal tunnel
      syndrome (CTS) and we compared it with that of the Korean version of the
      Disability of the Arm, Shoulder, and Hand Questionnaire (K-DASH), which was found
      to have a large degree of responsiveness after carpal tunnel release for Korean
      patients with CTS. METHODS: Thirty-seven patients with CTS prospectively
      completed the K-MHQ and the K-DASH before and 6 months after surgery. The
      responsiveness statistics were assessed for both the K-MHQ and the K-DASH by
      using the standardized response mean (SRM), which was defined as the mean change
      of the original scores after surgery divided by the standard deviation of the
      change. RESULTS: All domains of the K-MHQ significantly improved after carpal
      tunnel release (p < 0.001). The SRM for all scales but one (the aesthetics scale)
      showed large responsiveness of >= 0.8. The aesthetics scale showed medium
      responsiveness of 0.6. The combined function/symptom scale of the K-DASH
      significantly improved after surgery (p < 0.001). The SRM of the K-DASH revealed
      large responsiveness of 0.9. CONCLUSIONS: The K-MHQ was found to have a large
      degree of responsiveness after carpal tunnel release for Korean patients with
      CTS, which is comparable not only to the K-DASH, but also to the original version
      of the MHQ. The region-specific K-MHQ can be useful for outcomes research related
      to carpal tunnel surgery, especially for research comparing CTS with various
      other hand and wrist health conditions.

PMID- 24900904
TI  - Z-lengthening of the Achilles tendon with transverse skin incision.
AB  - BACKGROUND: The risk of various complications after Achilles tendon lengthening
      is mainly related to the length of surgical exposure and the lengthening method.
      A comprehensive technique to minimize the complications is required. METHODS: The
      treatment of Achilles tendon tightness in 57 patients (95 ankles) were performed
      by using a short transverse incision on a skin crease of the heel and by Z
      lengthening of the tendon. In the severe cases, two or three transverse incisions
      were required for greater lengthening of the tendon, and a serial cast or
      Ilizarov apparatus was applied for the gradual correction. The results of these
      95 ankles were compared to those of 18 ankles, which underwent percutaneous
      sliding lengthening, and to the 19 ankles, which received Z-lengthening with a
      medial longitudinal incision. RESULTS: The functional and cosmetic satisfaction
      was achieved among those who underwent the tendon lengthening with the new
      technique. The mean American Orthopaedic Foot & Ankle Society (AOFAS) score
      improved from 56.1 to 81.8. The second operations to correct recurrence were
      performed in the two cerebral palsy patients. CONCLUSIONS: The new technique has
      a low rate of complications such as scarring, adhesion, total transection,
      excessive lengthening, and recurrence of shortening. The excellent cosmesis and
      the short operation time are the additional advantages.

PMID- 24900905
TI  - Surgical treatment of congenital hallux varus.
AB  - BACKGROUND: The purpose of this study was to report outcomes of congenital hallux
      varus deformity after surgical treatment. METHODS: We evaluated ten feet of eight
      patients with a congenital hallux varus deformity, including four feet combined
      with a longitudinal epiphyseal bracket (LEB). There were seven male patients and
      one female patient with a mean age of 33 months (range, 7 to 103 months) at the
      time of surgery. Two patients were bilaterally involved. The mean duration of
      follow-up was 5.9 years (range, 2.3 to 13.8 years). Clinical outcomes were
      assessed according to the criteria of Phelps and Grogan. Surgical procedures
      included the Farmer procedure, the McElvenny procedure or an osteotomy at the
      first metatarsal or proximal phalanx. RESULTS: The clinical results were
      excellent in two feet, good in six and poor in two feet. The LEB was associated
      with hallux varus in four feet and were treated by osteotomy alone or in
      conjunction with soft tissue procedure. CONCLUSIONS: Congenital hallux varus was
      successfully corrected by surgery with overall favorable outcome. Preoperatively,
      a LEB should be considered as a possible cause of the deformity in order to
      prevent recurrent or residual varus after surgery.

PMID- 24900906
TI  - What is the usefulness of the fragmentation pattern of the femoral head in
      managing Legg-Calve-Perthes disease?
AB  - BACKGROUND: Within the lateral pillar classification of the Legg-Calve-Perthes
      (LCP) disease, hips seem quite variable in the pattern of fragmentation as seen
      in radiographs. The purpose of this study was to determine: if it is possible to
      reliably subdivide the lateral pillar groups into femoral head fragmentation
      patterns, and if such a subdivision of the lateral pillar groupings is clinically
      useful in managing LCP disease. METHODS: Two hundred and ninety-three
      anteroposterior radiographs taken at the maximal fragmentation stage (189 lateral
      pillar B, 57 B/C border, and 47 C hips; mean bone/chronologic age at the time of
      first visit, 6.2/7.9 years) and at skeletal maturity (mean age, 16.6 years) were
      analyzed. We distinguished 3 fragmentation patterns in each pillar group based on
      the region of major involvement. We tested the inter- and intraobserver
      reliability of our classification system and analyzed the relationships between
      the fragmentation patterns and the Stulberg outcomes as well as other factors
      such as surgical treatment and age. RESULTS: Inter- and intraobserver consistency
      in fragmentation pattern assignments was found to be substantial to excellent. A
      statistically significant trend (p = 0.001) in the proportion of Stulberg III or
      IV outcomes in comparison with Stulberg I and II was only found for the different
      fragmentation patterns in our lateral pillar B patients: fragmentation patterns
      having mainly lateral-central necrosis led to poor outcomes. No significant
      association was found between fragmentation patterns and Stulberg outcomes in
      pillar groups B/C border and C. CONCLUSIONS: Our results are consistent with the
      lateral pillar classification itself. Therefore, fragmentation patterns in each
      lateral pillar classification did not provide clinical usefulness in the
      management of LCP disease.

PMID- 24900907
TI  - Plain radiologic findings and chronological changes of incipient phase
      osteosarcoma overlooked by primary physicians.
AB  - BACKGROUND: We assessed the plain radiographic characteristics of 10 cases of
      osteosarcomas during the initial painful period that had been overlooked by a
      primary physician. In addition, we evaluated chronologic changes in radiographic
      findings from initial symptomatic period to the time of accurate diagnosis.
      METHODS: The clinical records were reviewed for clinical parameters including
      age, sex, location, presenting symptoms, initial diagnosis, duration from initial
      symptoms to definite diagnosis, and initial and follow-up plain radiographic
      findings of the lesion. RESULTS: Initial clinical diagnoses included a sprain in
      6, growing pain in 2, stress fracture in 1, and infection in 1 patient. Initial
      plain radiographic findings were trabecular destruction (100%), cortical
      disruption (60%), periosteal reaction (60%), and soft tissue mass (10%).
      Intramedullary matrix changes were osteosclerosis in 6 and osteolysis in 4
      patients. On progression, 4 cases with minimal sclerosis changed to osteoblastic
      lesion in 3 patients and osteolytic lesion in 1. Four cases with faint osteolytic
      foci transformed into osteolytic lesion in 3 and mixed pattern in 1. CONCLUSIONS:
      Notable plain radiologic findings of incipient-stage osteosarcoma include
      trabecular disruption along with faint osteosclerosis or osteolysis. In
      symptomatic patients with trabecular destruction, additional imaging study
      including magnetic resonance imaging should be performed to exclude osteosarcoma
      in the incipient phase, even without radiologic findings suggesting malignant
      tumor, such as cortical destruction or periosteal reaction.

PMID- 24900908
TI  - Total talar extrusion without soft tissue attachments.
AB  - Total talar extrusion without a soft tissue attachment is an extremely rare
      injury and is rarely reported. Appropriate treatment remains controversial. We
      describe the long-term outcomes of two patients who had complete talar extrusion
      without remaining soft tissue attachment treated with arthrodesis. Both of our
      patients had complications such as infection and progressive osteolysis. We
      suggest reimplantation of the extruded talus after thorough debridement as soon
      as possible as a reasonable option unless the talus is contaminated or missing,
      because an open wound may arise from inside to outside.

PMID- 24900909
TI  - A tenosynovial giant cell tumor arising from femoral attachment of the anterior
      cruciate ligament.
AB  - The localized type of tenosynovial giant cell tumor usually occurs on the palmar
      side of fingers and toes. Tenosynovial giant cell tumors of the tendon sheath are
      rarely intra-articular. We report a giant cell tumor of the tendon sheath arising
      from femoral attachment of the anterior cruciate ligament and its treatment with
      arthroscopy in a 28-year-old man.

PMID- 24900910
TI  - DNA damage and repair of human skin keratinocytes concurrently exposed to pyrene
      derivatives and UVA light.
AB  - Polycyclic aromatic hydrocarbons (PAHs), a class of mutagenic environmental
      contaminants, insert toxicity through both metabolic activation and light
      irradiation. Pyrene, one of the most widely studied PAHs, along with its mono
      substituted derivatives, 1-amino, 1-bromo, 1-hydroxy, and 1-nitropyrene, were
      chosen to study the effect of substituents on their phototoxicity, DNA damage and
      repair. Both alkaline Comet assay, which detects direct DNA damages, and Fpg
      endonuclease Comet assay, which detects oxidative DNA damages, were conducted at
      0, 2, 4, 8, and 24 h of incubation of the cells in minimal growth medium after
      concomitant exposure to pyrene derivatives and UVA light. All these compounds are
      photocytotoxic and the phototoxicity is both incubation time and PAH dose
      dependent; whereas, those without light are not toxic. The LC50 obtained are in
      the range of 3.5 - 9.3 uM. Cellular DNA damages, both direct and oxidative, are
      observed immediately after the cells are treated with UVA light and the pyrene
      derivatives at a concentration of 1.0 uM. The amount of DNA damages (both direct
      and oxidative) increase from 0 to 4 h of incubation. After 4 hours, subsequent
      damage induction declines, and this is perceived to be mainly through DNA repair.
      After longer incubation of 8 h, the damaged cellular DNA start to be repaired,
      resulting in greatly reduced amount of DNA damages, and the DNA damage reaches
      the minimum at 24 h of incubation. 1-Amopyrene and 1-hydroxypyrene cause more DNA
      oxidative damages immediately after the exposure (0 h of incubation), and these
      damages are repaired within the same timeframe as the other tested compounds. The
      oxidative DNA damages caused by 1-bromopyrene are repaired starting at 2 h of
      incubation, earlier than the damages caused by all the other compounds.

PMID- 24900911
TI  - Echinococcus granulosus Prevalence in Dogs in Southwest Nigeria.
AB  - Echinococcosis is a public health parasitic disease that is cosmopolitan
      (Echinococcus granulosus) in its distribution. Domestic dogs (Canis familiaris)
      have been recognised as the definitive host of the parasite. The present study
      was carried out to determine the prevalence of canine echinococcosis in Southwest
      Nigeria using direct enzyme linked immunosorbent assay (ELISA) to detect sera
      antigen. Two hundred and seventy-three (273) canine sera were tested for the
      presence of Echinococcus antigen. Purpose of keeping (hunting or companion), age
      (young or adult), and sex of each dog were considered during sampling. Total
      prevalence recorded was 12.45% (34/273). There was significant difference (P <
      0.05) between hunting (15.94%) and companion dogs (1.52%) but there was no
      significant difference (P > 0.05) between young and adult dogs. There was no
      association between sex and prevalence of canine echinococcosis. The result of
      this study established the presence of canine echinococcosis in Southwest
      Nigeria; thus there is the possibility of occurrence of zoonotic form of the
      disease (human cystic hydatid diseases) in the region. 

PMID- 24900912
TI  - Comparative analysis of the omics technologies used to study antimonial,
      amphotericin B, and pentamidine resistance in leishmania.
AB  - Leishmaniasis is a serious threat in developing countries due to its endemic
      nature and debilitating symptoms. Extensive research and investigations have been
      carried out to learn about the mechanism of drug resistance in Leishmania but
      results obtained in the laboratory are not in agreement with those obtained from
      the field. Also the lack of knowledge about the mode of action for a number of
      drugs makes the study of drug resistance more complex. A major concern in recent
      times has been regarding the role of parasitic virulence in drug resistance for
      Leishmania. Researchers have employed various techniques to unravel the facts
      about resistance and virulence in Leishmania. With advent of advanced and more
      specific means of detection, further hints about probable mechanisms of
      conferring resistance are expected. This review aims to provide a consolidated
      picture along with a comparative account of the work done so far to study the
      mechanism of antimony, amphotericin B, and pentamidine resistance using various
      techniques. 

PMID- 24900913
TI  - Antiplasmodial Effect of Anthocleista vogelii on Albino Mice Experimentally
      Infected with Plasmodium berghei berghei (NK 65).
AB  - The objective of the present study was to investigate the antiplasmodial effect
      of the ethanolic stem bark extract of Anthocleista vogelii at different doses in
      albino mice infected with Plasmodium berghei berghei (NK 65). Thirty-six mice
      were divided into six groups of six mice each. Five groups (B1-B3, D, and G) were
      infected with Plasmodium berghei berghei parasitized red blood cells. Groups D,
      H, and G served as the controls. Six days after infection, mice in groups B1, B2,
      and B3 were treated orally with 100, 200, and 400 mg/kg body weight of
      Anthocleista vogelii, respectively, for six executive days. Group D was treated
      with 5 mg/kg body weight of chloroquine while Group G was given distilled water.
      Group H was not infected and was not treated. It served as the normal control.
      The extracts exhibited significant (P < 0.05) dose-dependent chemosuppression of
      P. berghei. The extract exhibited average chemosuppressive effects of 48.5%,
      78.5%, and 86.6% at dose levels of 100, 200, and 400 mg/kg body weight,
      respectively. Phytochemical screening of the plant extract revealed the presence
      of saponins, cardiac glycosides, flavonoids, terpenes, alkaloids, and steroid.
      The acute toxicity (LD50) of the plant was estimated to be 3162 mg/kg body
      weight. It showed that the stem bark of A. vogelii possesses antiplasmodial
      property. 

PMID- 24900914
TI  - Investigation of PACAP Fragments and Related Peptides in Chronic Retinal
      Hypoperfusion.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective
      effects in different neuronal and retinal injuries. Retinal ischemia can be
      effectively modelled by permanent bilateral common carotid artery occlusion
      (BCCAO), which causes chronic hypoperfusion-induced degeneration in the entire
      rat retina. The retinoprotective effect of PACAP 1-38 and VIP is well-established
      in ischemic retinopathy. However, little is known about the effects of related
      peptides and PACAP fragments in ischemic retinopathy. The aim of the present
      study was to investigate the potential retinoprotective effects of different
      PACAP fragments (PACAP 4-13, 4-22, 6-10, 6-15, 11-15, and 20-31) and related
      peptides (secretin, glucagon) in BCCAO-induced ischemic retinopathy. Wistar rats
      (3-4 months old) were used in the experiment. After performing BCCAO, the right
      eyes of the animals were treated with PACAP fragments or related peptides
      intravitreal (100 pM), while the left eyes were injected with saline serving as
      control eyes. Sham-operated (without BCCAO) rats received the same treatment.
      Routine histology was performed 2 weeks after the surgery; cells were counted and
      the thickness of retinal layers was compared. Our results revealed significant
      neuroprotection by PACAP 1-38 but did not reveal retinoprotective effect of the
      PACAP fragments or related peptides. These results suggest that PACAP 1-38 has
      the greatest efficacy in ischemic retinopathy. 

PMID- 24900915
TI  - Selective Age Effects on Visual Attention and Motor Attention during a Cued
      Saccade Task.
AB  - Objective. Visual information is often used to guide purposeful movement.
      However, older adults have impaired responses to visual information, leading to
      increased risk for injuries and potential loss of independence. We evaluated
      distinct visual and motor attention contributions to a cued saccade task to
      determine the extent to which aging selectively affects these processes. Methods.
      Nineteen healthy young (18-28 years) and 20 older (60-90 years) participants
      performed a cued saccade task under two conditions. We challenged motor attention
      by changing the number of possible saccade targets (1 or 6). Results. Older
      adults had difficulty in inhibiting unwanted eye movements and had greater eye
      movement inaccuracy in the hard condition when compared to the younger adults and
      to the easy condition. Also, an inverse relation existed between performance on
      the visual and motor components of the task in older adults, unlike younger
      adults. Conclusions. Older adults demonstrated difficulty in both inhibiting
      irrelevant saccade targets and selecting correct saccade endpoints during more
      complex tasks. The shift in relations among attention measures between the
      younger and older participants may indicate a need to prioritize attentional
      resources with age. These changes may impact an older adult's ability to function
      in complex environments. 

PMID- 24900916
TI  - Time-related alteration in flow- (shear stress-) mediated remodeling in
      resistance arteries from spontaneously hypertensive rats.
AB  - Hypertension is a major risk factor for cardiovascular disorders. As flow
      mediated outward remodeling has a key role in postischemic revascularization, we
      investigated this remodeling in mesenteric resistance arteries of normotensive
      (WKY) and spontaneously hypertensive rats (SHRs) aged 3 to 9 months. Sequential
      ligation of mesenteric resistance arteries allowed modifying blood flow in vivo,
      thus exposing arteries to low, normal, or high flow. After 1, 3, 8, or 24 weeks,
      arteries were isolated for in vitro study. High flow (HF) induced outward
      hypertrophic remodeling in WKY rats after 1 week and persisted until 24 weeks
      without change in wall to lumen ratio. In SHRs, diameter increase was delayed,
      occurring only after 3 weeks. Nevertheless, it was reduced at 8 weeks and no
      longer significant after 24 weeks. In parallel, media cross-section area
      increased more with time in SHRs than in WKY rats and this was associated with
      increased contractility and oxidative stress with decreased NO-dependent
      relaxation. Low flow induced progressive inward remodeling until 24 weeks in both
      strains with excessive hypertrophy in SHRs. Thus, a chronic increase in flow
      induced transitory diameter expansion and long-lasting hypertrophy in SHRs. This
      could contribute to the higher susceptibility of hypertensive subjects to
      ischemic diseases. 

PMID- 24900917
TI  - Optimization of Enzymatic Saccharification of Alkali Pretreated Parthenium sp.
      Using Response Surface Methodology.
AB  - Parthenium sp. is a noxious weed which threatens the environment and biodiversity
      due to its rapid invasion. This lignocellulosic weed was investigated for its
      potential in biofuel production by subjecting it to mild alkali pretreatment
      followed by enzymatic saccharification which resulted in significant amount of
      fermentable sugar yield (76.6%). Optimization of enzymatic hydrolysis variables
      such as temperature, pH, enzyme, and substrate loading was carried out using
      central composite design (CCD) in response to surface methodology (RSM) to
      achieve the maximum saccharification yield. Data obtained from RSM was validated
      using ANOVA. After the optimization process, a model was proposed with predicted
      value of 80.08% saccharification yield under optimum conditions which was
      confirmed by the experimental value of 85.80%. This illustrated a good agreement
      between predicted and experimental response (saccharification yield). The
      saccharification yield was enhanced by enzyme loading and reduced by temperature
      and substrate loading. This study reveals that under optimized condition, sugar
      yield was significantly increased which was higher than earlier reports and
      promises the use of Parthenium sp. biomass as a feedstock for bioethanol
      production. 

PMID- 24900919
TI  - Bedside assessment of tissue oxygen saturation monitoring in critically ill
      adults: an integrative review of the literature.
AB  - Objective. Tissue oxygen saturation (StO2) monitoring is a noninvasive technology
      with the purpose of alerting the clinician of peripheral hypoperfusion and the
      onset of tissue hypoxia. This integrative review examines the rigor and quality
      of studies focusing on StO2 monitoring in adult critically ill patients.
      Background. Clinicians must rapidly assess adverse changes in tissue perfusion
      while minimizing potential complications associated with invasive monitoring. The
      noninvasive measurement of tissue oxygen saturation is based on near-infrared
      spectroscopy (NIRS), an optical method of illuminating chemical compounds which
      absorb, reflect, and scatter light directed at that compound. Methods. An
      integrative review was conducted to develop a context of greater understanding
      about complex topics. An Integrative review draws on multiple experimental and
      nonexperimental research methodologies. Results. Fourteen studies were graded at
      the C category. None reported the use of probability sampling or demonstrated a
      cause-and-effect relationship between StO2 values and patient outcomes.
      Conclusions. Future research should be based on rigorous methods of sampling and
      design in order to enhance the internal and external validity of the findings. 

PMID- 24900920
TI  - Suitability, efficacy, and safety of vernakalant for new onset atrial
      fibrillation in critically ill patients.
AB  - Objectives. This study investigates the suitability, safety, and efficacy of
      vernakalant in critically ill patients with new onset atrial fibrillation (AF)
      after cardiac surgery. Methods. Patients were screened for inclusion and
      exclusion criteria according to the manufacturers' recommendations. Included
      patients were treated with 3 mg/kg of vernakalant over 10 min and, if
      unsuccessful, a second dose of 2 mg/kg. Blood pressure was measured continuously
      for 2 hours after treatment. Results. Of the 191 patients screened, 159 (83%)
      were excluded, most importantly due to hemodynamic instability (59%). Vernakalant
      was administered to 32 (17% of the screened) patients. Within 6 hours, 17 (53%)
      patients converted to sinus rhythm. Blood pressure did not decrease significantly
      10, 30, 60, and 120 minutes after the vernakalant infusion. However, 11 patients
      (34%) experienced a transient decrease in mean arterial blood pressure <60 mmHg.
      Other adverse events included nausea (n = 1) and bradycardia (n = 2).
      Conclusions. Applying the strict inclusion and exclusion criteria provided by the
      manufacturer, only a minority of postoperative ICU patients with new onset AF
      qualified for vernakalant. Half of the treated patients converted to sinus
      rhythm. The drug was well tolerated, but close heart rate and blood pressure
      monitoring remains recommended. 

PMID- 24900918
TI  - Autoimmunity and the gut.
AB  - Autoimmune diseases have increased dramatically worldwide since World War II.
      This is coincidental with the increased production and use of chemicals both in
      industrial countries and agriculture, as well as the ease of travel from region
      to region and continent to continent, making the transfer of a pathogen or
      pathogens from one part of the world to another much easier than ever before. In
      this review, triggers of autoimmunity are examined, principally environmental.
      The number of possible environmental triggers is vast and includes chemicals,
      bacteria, viruses, and molds. Examples of these triggers are given and include
      the mechanism of action and method by which they bring about autoimmunity. 

PMID- 24900921
TI  - Gender-related barriers and delays in accessing tuberculosis diagnostic and
      treatment services: a systematic review of qualitative studies.
AB  - Background. Tuberculosis (TB) remains a significant global public health problem
      with known gender-related (male versus female) disparities. We reviewed the
      qualitative evidence (written/spoken narrative) for gender-related differences
      limiting TB service access from symptom onset to treatment initiation. Methods.
      Following a systematic process, we searched 12 electronic databases, included
      qualitative studies that assessed gender differences in accessing TB diagnostic
      and treatment services, abstracted data, and assessed study validity. Using a
      modified "inductive coding" system, we synthesized emergent themes within defined
      barriers and delays limiting access at the individual and provider/system levels
      and examined gender-related differences. Results. Among 13,448 studies, 28
      studies were included. All were conducted in developing countries and assessed
      individual-level barriers; 11 (39%) assessed provider/system-level barriers, 18
      (64%) surveyed persons with suspected or diagnosed TB, and 7 (25%) exclusively
      surveyed randomly sampled community members or health care workers. Each barrier
      affected both genders but had gender-variable nature and impact reflecting
      sociodemographic themes. Women experienced financial and physical dependence,
      lower general literacy, and household stigma, whereas men faced work-related
      financial and physical barriers and community-based stigma. Conclusions. In
      developing countries, barriers limiting access to TB care have context-specific
      gender-related differences that can inform integrated interventions to optimize
      TB services. 

PMID- 24900922
TI  - Induction chemotherapy in technically unresectable locally advanced carcinoma of
      maxillary sinus.
AB  - Background. Locally advanced carcinoma of maxillary sinus has been historically
      reported to have poor prognosis. We evaluated the role of NACT in improving the
      outcome in these patients. Methods. 41 patients with locally advanced technically
      unresectable (stage IVa) or unresectable maxillary carcinoma (stage IVb) were
      treated with induction chemotherapy between 2008 and 2011. The demographic
      profile, response and toxicity of chemotherapy, definitive treatment received,
      progression free survival (PFS), and overall survival (OS) were analyzed.
      Univariate and multivariate analysis were performed to determine factors
      associated with PFS and OS. Results. The chemotherapy included two drugs
      (platinum and taxane) in 34 patients (82.9%) and three drugs (platinum, taxane,
      and 5 FU) in 7 (17.1%). There was no complete response seen in any of the
      patients, stable disease in 18 (43.9%), partial response in 16 (39%), and
      progression in 7 (17.1%) patients. After induction, the treatment planned
      included surgery in 12 (29.3%), CT-RT in 24 (58.5%), radical RT in 1 (2.4%),
      palliative RT in 1 (2.4%), and palliative chemotherapy in 3 (7.3%) patients.
      Overall, the median PFS was 10.0 months. The OS at 24 months and 36 months was
      41% and 35%, respectively. Conclusion. In unresectable maxillary carcinoma,
      induction chemotherapy has clinically significant benefit with acceptable
      toxicity. 

PMID- 24900923
TI  - Comparison of transperineal mapping biopsy results with whole-mount radical
      prostatectomy pathology in patients with localized prostate cancer.
AB  - Objective. We sought to evaluate the accuracy of transperineal mapping biopsy
      (TMB) by comparing it to the pathology specimen of patients who underwent radical
      prostatectomy (RP) for localized prostate cancer. Methods. From March 2007 to
      September 2009, 78 men at a single center underwent TMB; 17 of 78 subsequently
      underwent RP. TMB cores were grouped into four quadrants and matched to data from
      RP whole-mount slides. Gleason score, tumor location and volume, cross-sectional
      area, and maximal diameter were measured; sensitivity and specificity were
      assessed. Results. For the 17 patients who underwent RP, TMB revealed 12 (71%)
      had biopsy Gleason grades >= 3 + 4 and 13 (76%) had bilateral disease. RP
      specimens showed 14 (82%) had Gleason scores >= 3 + 4 and 13 (76%) had bilateral
      disease. Sensitivity and specificity of TMB for prostate cancer detection were
      86% (95% confidence interval [CI] 72%-94%) and 83% (95% CI 62%-95%),
      respectively. Four quadrants negative for cancer on TMB were positive on
      prostatectomy, and six positive on TMB were negative on prostatectomy.
      Conclusion. TMB is a highly invasive procedure that can accurately detect and
      localize prostate cancer. These findings help establish baseline performance
      characteristics for TMB and its utility for organ-sparing strategies. 

PMID- 24900925
TI  - The abdomen in "thoracoabdominal" cannot be ignored: abdominal compartment
      syndrome complicating extracorporeal life support.
AB  - Extracorporeal life support (ECLS) is an incredible life-saving measure that is
      being used ever more frequently in the care of the critically ill. Management of
      these patients requires extreme vigilance on the part of the care providers in
      recognizing and addressing the complications and challenges that may arise. We
      present a case of overt abdominal compartment syndrome (ACS) in a previously well
      young male on ECLS with a history of trauma, submersion, hypothermia, and no
      intra-abdominal injuries. The patient developed ACS soon after ECLS was initiated
      which resulted in drastically compromised flow rates. Taking into account the
      patient's critical status, an emergent laparotomy was performed in the intensive
      care unit which successfully resolved the ACS and restored ECLS flow. The patient
      had an unremarkable course following and was weaned off ECLS but unfortunately
      died from his original anoxic injury. This case highlights several salient
      points: first, care of patients on ECLS is challenging and multiple etiologies
      can affect our ability to manage these patients; second, intra-abdominal
      pressures should be monitored liberally in the critically ill, especially in
      patients on ECLS; third, protocols for emergent operative treatment outside of
      traditional operating rooms should be established and care providers should be
      prepared for these situations. 

PMID- 24900926
TI  - Constricted canals: a new strategy to overcome this challenge.
AB  - Negotiation of constricted canals can be a challenge during endodontic treatment.
      Over the years, several strategies have been presented in order to overcome the
      difficulties imposed by this anatomical feature. This paper presents three cases
      using a different protocol from that recommended by the manufacturer of the
      Protaper System in order to facilitate the negotiation of constricted canals.
      These cases suggest that the modified protocol shown is able to perform the
      shaping process with less resistance, reducing the risk of instrument separation
      and performing an effective process to reach the apical thirds in constricted
      canals. 

PMID- 24900927
TI  - Eruption of odontomas into the oral cavity: a report of 2 cases.
AB  - Odontomas are the commonest odontogenic tumors of the oral cavity and are by
      nature asymptomatic. They consist mainly of dental tissue that may or may not be
      arranged in an orderly fashion. Their presence is often detected accidentally or
      due to the presence of a dental disturbance such as an unerupted tooth. The very
      rarity of odontomas erupting into the oral cavity validates the need for more
      current literature on the phenomenon. Our report of two cases aims to present and
      discuss the rare event of an erupting odontoma with the dental community. 

PMID- 24900928
TI  - Continued root formation after delayed replantation of an avulsed immature
      permanent tooth.
AB  - Introduction. Tooth avulsion in the young permanent dentition is a frequent
      finding, and its prognosis depends on the treatment of the avulsed tooth before
      replantation, the extra-alveolar time, the storage medium, and the patient's
      general health. The present report describes management of an immature avulsed
      lower central incisor 90 minutes after the accident. Methods. A right lower
      central incisor of a 7-year-old girl was avulsed, and it was soaked in a glass of
      milk. 90 minutes after avulsion, replantation was performed, and the tooth was
      splinted; but after two weeks the replanted tooth's pulp was necrotic. Thus,
      endodontic treatment was performed and root canal was filled using a calcium
      hydroxide and iodoform paste (Metapex). Three months later, the intracanal
      medication was washed out and the canal was sealed using an apical plug of
      calcium enriched mixture (CEM) cement. Results. 20 months after replantation the
      tooth was completely asymptomatic, with physiologic mobility. Also, continued
      root formation including an apical segment beyond the artificial apical plug was
      observed. Conclusion. Creation of an appropriate apical barrier following the
      disinfection of root canal system promoted continued root-end growth in a
      replanted immature permanent tooth. 

PMID- 24900929
TI  - Intrathecal administration of high-titer cytomegalovirus immunoglobulin for
      cytomegalovirus meningitis.
AB  - Cytomegalovirus (CMV) central nervous system disease after hematopoietic stem
      cell transplantation (HSCT) is a rare but life-threatening complication. Here, we
      report a patient who developed CMV meningitis after HSCT and was treated with the
      combination therapy of intrathecal high-titer CMV immunoglobulin and antiviral
      drugs. A 38-year-old man with myelodysplastic syndrome received a cord blood
      transplant after graft failure. On day 147, he was diagnosed with CMV meningitis
      based on pleocytosis and CMV DNA in the cerebrospinal fluid (CSF). Intravenous
      ganciclovir, foscarnet, and immunoglobulin were administered; however, CMV DNA in
      the CSF was continuously detected. The addition of intrathecal high-titer CMV
      immunoglobulin resulted in CMV DNA in the CSF becoming undetectable. On day 241,
      CMV DNA in the CSF was detected again, but both intrathecal immunoglobulin and
      intravenous ganciclovir led to its disappearance. No adverse effects related to
      intrathecal administration were observed. The intrathecal administration of
      immunoglobulin may be safe and effective for CMV meningitis. 

PMID- 24900930
TI  - A presentation of cerebritis secondary to granulomatosis with polyangiitis
      (wegener).
AB  - Neurological manifestations of GPA are common, most frequently as a peripheral
      neuropathy. Cerebritis as a principal presentation is extremely rare. We report a
      patient who presented with subacute progression of ataxia, confusion, and vacant
      episodes. An MRI of her brain showed bilateral signal abnormalities in the
      cingulate and superior sagittal gyrus while a staging CT revealed a mass in the
      right upper lobe of the patient's lung with a satellite nodule. C-ANCA antibodies
      specific for PR3 at high titres were positive and a diagnosis of GPA was made.
      The patient was commenced on intravenous methylprednisolone followed by
      cyclophosphamide and responded well to treatment. GPA is a rare and treatable
      differential diagnosis for confused patients with acute or subacute neurological
      features and unusual MRI findings. 

PMID- 24900924
TI  - Effects of diet on brain plasticity in animal and human studies: mind the gap.
AB  - Dietary interventions have emerged as effective environmental inducers of brain
      plasticity. Among these dietary interventions, we here highlight the impact of
      caloric restriction (CR: a consistent reduction of total daily food intake),
      intermittent fasting (IF, every-other-day feeding), and diet supplementation with
      polyphenols and polyunsaturated fatty acids (PUFAs) on markers of brain
      plasticity in animal studies. Moreover, we also discuss epidemiological and
      intervention studies reporting the effects of CR, IF and dietary polyphenols and
      PUFAs on learning, memory, and mood. In particular, we evaluate the gap in
      mechanistic understanding between recent findings from animal studies and those
      human studies reporting that these dietary factors can benefit cognition, mood,
      and anxiety, aging, and Alzheimer's disease-with focus on the enhancement of
      structural and functional plasticity markers in the hippocampus, such as
      increased expression of neurotrophic factors, synaptic function and adult
      neurogenesis. Lastly, we discuss some of the obstacles to harnessing the
      promising effects of diet on brain plasticity in animal studies into effective
      recommendations and interventions to promote healthy brain function in humans.
      Together, these data reinforce the important translational concept that diet, a
      modifiable lifestyle factor, holds the ability to modulate brain health and
      function. 

PMID- 24900931
TI  - Recurrent gliosarcoma in pregnancy.
AB  - Gliosarcoma is a rare tumor of the central nervous system and it constitutes
      about 1 to 8% of all malignant gliomas. In this report we are presenting a
      recurrent gliosarcoma case during a pregnancy in a 30-year-old woman. This is the
      first report presenting gliosarcoma in the pregnancy. 

PMID- 24900932
TI  - Immature teratoma after three laparoscopic resections for mature cystic
      teratomas.
AB  - We report a case in which an immature teratoma developed following three previous
      resections for mature cystic teratomas. The patient was a 26-year-old nulliparous
      woman with a regular menstrual cycle. Twelve years earlier, she had consulted a
      pediatrician for complaints of lower abdominal pain. Bilateral cystic teratomas
      were suspected and she underwent a left salpingo-oophorectomy and a right
      cystectomy laparoscopically, and bilateral mature cystic teratomas were diagnosed
      histologically. She underwent a right cystectomy twice afterwards and mature
      cystic teratomas were diagnosed. Three years after the third surgery, a regular
      checkup performed annually for ovarian cyst recurrence revealed a 9.3 cm ovarian
      cyst by ultrasonography without marker elevation or complaint of symptoms.
      Magnetic resonance imaging (MRI) showed a 10 cm multilocular cyst, including a
      part with heterogeneous medium and high-signal intensity on T2-weighted images,
      which revealed enhancement on dynamic contrast-enhanced MRI unlike the previous
      images. Ovarian tumors, including immature teratomas and malignancy, were
      considered. She had a strong wish to undergo laparoscopic surgery. She was
      diagnosed with an immature teratoma, grade 1 of the right ovary. Although the
      frequency of recurrence of immature teratomas after resection of mature cystic
      teratomas is very low, regular checkups are necessary because there may be no
      associated symptoms. 

PMID- 24900934
TI  - Cervicofacial Surgical Emphysema following Tonsillectomy.
AB  - We report the case of a patient who developed cervicofacial subcutaneous
      emphysema following a routine tonsillectomy. An 18-year-old male with swallowing
      difficulties underwent a tonsillectomy and developed swelling of the right side
      of his neck and face 36 hours after surgery. A neck X-ray revealed subcutaneous
      emphysema. Unlike similar previously published cases, there were no postoperative
      issues of coughing, straining, or use of positive pressure ventilation. The
      complication also occurred after a considerable length of time. Further
      complications may include pneumothorax and pneumomediastinum and these should be
      excluded. 

PMID- 24900935
TI  - Delayed presentation of traumatic right-sided diaphragmatic hernia after
      abdominoplasty.
AB  - Traumatic diaphragmatic hernias are rare and challenging to diagnose. Following
      trauma, diagnosis may occur immediately or in a delayed fashion. It is believed
      that left traumatic diaphragmatic hernias are more common as a result of the
      protective right-sided anatomic lie of the liver. If unrecognized, traumatic
      diaphragmatic injuries are subject to enlarge over time as a result of the normal
      pressure changes observed between the thoracic and abdominal cavities.
      Additionally, abrupt changes to the pressure gradients, such as those which occur
      with positive pressure ventilation or surgical manipulation of the abdominal
      wall, can act as a nidus for making an asymptomatic hernia symptomatic. We report
      our experience with a delayed traumatic right-sided diaphragmatic hernia
      presenting with large bowel incarceration two months after abdominoplasty. In our
      review of the literature, we were unable to find any reports of delayed
      presentation of a traumatic right-sided diaphragmatic hernia occurring acutely
      following abdominoplasty. 

PMID- 24900936
TI  - Paratesticular inflammatory myofibroblastic tumor in a pediatric patient.
AB  - Although rare, paratesticular inflammatory myofibroblastic tumor (IMT) represents
      the second most common paratesticular mass after adenomatoid tumor and comprises
      roughly 6% of such lesions. Only approximately four cases have been reported in
      patients younger than 18 years of age. We report an incidentally discovered
      paratesticular IMT in a 17-year-old male successfully treated with wide excision
      and testis sparing. To our knowledge, no recurrence has been reported after
      complete excision of paratesticular IMT; however, continued follow-up is
      recommended. 

PMID- 24900933
TI  - Reversible posterior encephalopathy syndrome secondary to sunitinib.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is clinical radiologic
      condition associated with neurological symptoms and cerebral white matter edema.
      It has been associated with uncontrolled hypertension, eclampsia,
      immunosuppressants, and more recently the use of antiangiogenic drugs. Sunitinib
      is an inhibitor of the vascular endothelial growth factor receptor widely used in
      the treatment of metastatic renal cell carcinoma (RCC). We report a rare case of
      RPLS occurring on therapy with sunitinib in a patient with RCC. Our aim is to
      highlight the importance of considering RPLS as a diagnostic possibility and to
      hold sunitinib for RCC patients presenting with neurologic symptoms. 

PMID- 24900937
TI  - Ultrasensitive Detection of Ferulic Acid Using Poly(diallyldimethylammonium
      chloride) Functionalized Graphene-Based Electrochemical Sensor.
AB  - The electrochemical redox of ferulic acid (FA) was investigated systematically by
      cyclic voltammetry (CV) with a poly(diallyldimethylammonium chloride)
      functionalized graphene-modified glassy carbon electrode (PDDA-G/GCE) as a
      working electrode. A simple and sensitive differential pulse voltammetry (DPV)
      technique was proposed for the direct quantitative determination of FA in
      Angelica sinensis and spiked human urine samples for the first time. The
      dependence of the intensities of currents and potentials on nature of the
      supporting electrolyte, pH, scan rate, and concentration was investigated. Under
      optimal conditions, the proposed sensor exhibited excellent electrochemical
      sensitivity to FA, and the oxidation peak current was proportional to FA
      concentration in the range of 8.95 * 10(-8) M ~5.29 * 10(-5) M, with a relatively
      low detection limit of 4.42 * 10(-8) M. This fabricated sensor also displayed
      acceptable reproducibility, long-term stability, and high selectivity with
      negligible interferences from common interfering species. Besides, it was applied
      to detect FA in Angelica sinensis and biological samples with satisfactory
      results, making it a potential alternative tool for the quantitative detection of
      FA in pharmaceutical analysis. 

PMID- 24900938
TI  - Daily sedative interruption versus intermittent sedation in mechanically
      ventilated critically ill patients: a randomized trial.
AB  - BACKGROUND: Daily sedative interruption and intermittent sedation are effective
      in abbreviating the time on mechanical ventilation. Whether one is superior to
      the other has not yet been determined. Our aim was to compare daily interruption
      and intermittent sedation during the mechanical ventilation period in a low nurse
      staffing ICU. METHODS: Adult patients expected to need mechanical ventilation for
      more than 24 hours were randomly assigned, in a single center, either to daily
      interruption of continuous sedative and opioid infusion or to intermittent
      sedation. In both cases, our goal was to maintain a Sedation Agitation Scale
      (SAS) level of 3 or 4; that is patients should be calm, easily arousable or
      awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator
      free days in 28 days. Secondary outcomes were ICU and hospital mortality,
      incidence of delirium, nurse workload, self-extubation and psychological distress
      six months after ICU discharge. RESULTS: A total of 60 patients were included.
      There were no differences in the ventilator-free days in 28 days between daily
      interruption and intermittent sedation (median: 24 versus 25 days, P = 0.160).
      There were also no differences in ICU mortality (40 versus 23.3%, P = 0.165),
      hospital mortality (43.3 versus 30%, P = 0.284), incidence of delirium (30 versus
      40%, P = 0.472), self-extubation (3.3 versus 6.7%, P = 0.514), and psychological
      stress six months after ICU discharge. Also, the nurse workload was not different
      between groups, but it was reduced on day 5 compared to day 1 in both groups
      (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1
      versus 39 on day 5, P < 0.001; NAS in daily interruption group was 53 on day 1
      versus 38 on day 5, P < 0.001). Fentanyl and midazolam total dosages per patient
      were higher in the daily interruption group. The tidal volume was higher in the
      intermittent sedation group during the first five days of ICU stay. CONCLUSIONS:
      There was no difference in the number of ventilator-free days in 28 days between
      both groups. Intermittent sedation was associated with lower sedative and opioid
      doses. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00824239.

PMID- 24900939
TI  - Raised serum proinflammatory cytokines in Alzheimer's disease with depression.
AB  - The purpose of the present study was to identify the changes in the levels of
      proinflammatory cytokines like IL-1beta, IL-6 and TNF-alpha in peripheral
      circulation in Alzheimer's disease (AD) subjects and to correlate these with
      associated depression and cognitive deficit. Fifty five AD subjects and thirty
      seven age and sex matched controls were included in the study. The AD patients
      were grouped as AD with depression (n= 31) and AD without depression (n= 24). The
      serum levels of IL-1beta, IL-6 and TNF-alpha were determined by immunoassay by
      commercially available kits. The serum levels of IL-6 and TNF-alpha were elevated
      in AD patients with depression compared to control (p<0.001) or AD without
      depression (p<0.001). The serum level of IL-1beta was higher in AD patients with
      or without depression as compared to controls. Furthermore, a strong inverse
      correlation was observed between the MMSE scores and serum levels of IL-6 or TNF
      alpha in AD subjects with depression. The study highlights the important role of
      peripheral IL-6 and TNF-alpha in AD associated depression and cognitive deficits.

PMID- 24900940
TI  - Hip fractures in a geriatric population - rehabilitation based on patients needs.
AB  - With an increased life expectancy in humans and thus an increase in the number of
      the elderly population, the frequency of hip fractures will rise as well. Aside
      from a higher incidence, hip fractures in a geriatric population is a significant
      problem due to the possible onset of severe and in some cases dramatic
      complications and consequences. The primary purpose of treatment and
      rehabilitation in the elderly after a hip fracture is to improve an individual's
      quality of life. It is important to underline that principles and methods of
      functional restoration after hip fracture should consider careful planning of a
      rehabilitation program individually for every patient and its implementation with
      respect to decisions made by the rehabilitation team. 

PMID- 24900941
TI  - Strength and endurance training prescription in healthy and frail elderly.
AB  - Aging is associated with declines in the neuromuscular and cardiovascular
      systems, resulting in an impaired capacity to perform daily activities. Frailty
      is an age-associated biological syndrome characterized by decreases in the
      biological functional reserve and resistance to stressors due to changes in
      several physiological systems, which puts older individuals at special risk of
      disability. To counteract the neuromuscular and cardiovascular declines
      associated with aging, as well as to prevent and treat the frailty syndrome, the
      strength and endurance training seems to be an effective strategy to improve
      muscle hypertrophy, strength and power output, as well as endurance performance.
      The first purpose of this review was discuss the neuromuscular adaptations to
      strength training, as well as the cardiovascular adaptations to endurance
      training in healthy and frail elderly subjects. In addition, the second purpose
      of this study was investigate the concurrent training adaptations in the elderly.
      Based on the results found, the combination of strength and endurance training
      (i.e., concurrent training) performed at moderate volume and moderate to high
      intensity in elderly populations is the most effective way to improve both
      neuromuscular and cardiorespiratory functions. Moreover, exercise interventions
      that include muscle power training should be prescribed to frail elderly in order
      to improve the overall physical status of this population and prevent disability.

PMID- 24900943
TI  - Link between PI3K/AKT/PTEN Pathway and NOX Proteinin Diseases.
AB  - Accumulating evidence has revealed that thePI3K/AKT/PTENpathway acts as a pivotal
      determinant of cell fate regarding senescence and apoptosis, which is mediated by
      intracellular reactive oxygen species (ROS) generation. NADPH oxidase (NOX)
      family of enzymes generates the ROS. The regulation of NOX enzymes is complex,
      with many members of this family exhibiting complexity in terms of subunit
      composition, cellular location, and tissue-specific expression. Cells are
      continuously exposed to the ROS, which represent mutagens and are thought to be a
      major contributor to several diseases including cancer and aging process.
      Therefore, cellular ROS sensing and metabolism are firmly regulated by a variety
      of proteins involved in the redox mechanism. In this review, the roles of
      oxidative stress in PI3K/AKT/PTEN signaling are summarized with a focus on the
      links between the pathways and NOX protein in several diseases including cancer
      and aging. 

PMID- 24900942
TI  - Aging is not a disease: implications for intervention.
AB  - Aging of biological systems occurs in spite of numerous complex pathways of
      maintenance, repair and defense. There are no gerontogenes which have the
      specific evolutionary function to cause aging. Although aging is the common cause
      of all age-related diseases, aging in itself cannot be considered a disease. This
      understanding of aging as a process should transform our approach towards
      interventions from developing illusory anti-aging treatments to developing
      realistic and practical methods for maintaining health throughout the lifespan.
      The concept of homeodynamic space can be a useful one in order to identify a set
      of measurable, evidence-based and demonstratable parameters of health, robustness
      and resilience. Age-induced health problems, for which there are no other clear
      cut causative agents, may be better tackled by focusing on health mechanisms and
      their maintenance, rather than only disease management and treatment. Continuing
      the disease-oriented research and treatment approaches, as opposed to health
      oriented and preventive strategies, are economically, socially and
      psychologically unsustainable. 

PMID- 24900944
TI  - Lifestyle and Advanced Glycation End Products (AGEs) Burden: Its Relevance to
      Healthy Aging.
AB  - Uncontrolled continued exposure to oxidative stress is a precursor to many
      chronic diseases including cancer, diabetes, degenerative disorders and
      cardiovascular diseases. Of the many known mediators of oxidative stress,
      reactive oxygen species (ROS) and advanced glycation end products (AGEs) are the
      most studied. In the present review, we have summarized current data on the
      origin of circulating AGEs, discussed issues associated with reliable assessment
      of its steady state level, and changes in its level with age and select metabolic
      diseases. Lastly, we have made recommendations about life style changes that may
      decrease AGEs burden to promote healthy aging. 

PMID- 24900945
TI  - Challenges and Practices in Building and Implementing Biosafety and Biosecurity
      Programs to Enable Basic and Translational Research with Select Agents.
AB  - Select agent research in the United States must meet federally-mandated
      biological surety guidelines and rules which are comprised of two main
      components: biosecurity and biosafety. Biosecurity is the process employed for
      ensuring biological agents are properly safeguarded against theft, loss,
      diversion, unauthorized access or use/release. Biosafety is those processes that
      ensure that operations with such agents are conducted in a safe, secure and
      reliable manner. As such, a biological surety program is generally concerned with
      biological agents that present high risk for adverse medical and/or agricultural
      consequences upon release outside of proper containment. The U.S. Regional and
      National Biocontainment Laboratories (RBL, NBL) represent expertise in this type
      of research, and are actively engaged in the development of programs to address
      these critical needs and federal requirements. While this comprises an ongoing
      activity for the RBLs, NBLs and other facilities that handle select agents as new
      guidelines and regulations are implemented, the present article is written with
      the goal of presenting a simplified yet comprehensive review of these
      requirements. Herein, we discuss the requirements and the various activities that
      the RBL/NBL programs have implemented to achieve these metrics set forth by
      various agencies within the U.S. Federal government.

PMID- 24900946
TI  - NK Cells and MSCs: Possible Implications for MSC Therapy in Renal
      Transplantation.

PMID- 24900947
TI  - Genotyping Tools for Mycobacterium ulcerans-Drawbacks and Future Prospects.
AB  - Mycobacterium ulcerans infection (Buruli ulcer) is a neglected but treatable skin
      disease endemic in over 30 countries. M. ulcerans is an environmental
      mycobacteria with an elusive mode of transmission to humans. Ecological and
      Molecular epidemiological studies to identify reservoirs and transmission vectors
      are important for source tracking infections especially during outbreaks and
      elucidating transmission routes. Research efforts have therefore focused on
      genotyping strains of the mycobacteria from clinical and environmental samples.
      This review discusses genotyping tools for differentiating M. ulcerans strains
      from other environmental and Mycolactone Producing Mycobacteria (MPMs). We
      highlight tools that have been adapted from related fields and propose ways these
      could be enhanced to resolve intra-species variation for epidemiological,
      transmission, evolutionary studies, and detection of emerging drug resistant
      strains. In the wake of increasing cases of Buruli ulcer, cumulative efforts
      including improvement in diagnostic methods and fine-tuning of genotyping tools
      are crucial to complement public health efforts in reducing infections.

PMID- 24900948
TI  - Low-dose morphine elicits ventilatory excitant and depressant responses in
      conscious rats: Role of peripheral MU-opioid receptors.
AB  - The systemic administration of morphine affects ventilation via a mixture of
      central and peripheral actions. The aims of this study were to characterize the
      ventilatory responses elicited by a low dose of morphine in conscious rats; to
      determine whether tolerance develops to these responses; and to determine the
      potential roles of peripheral MU-opioid receptors (MU-ORs) in these responses.
      Ventilatory parameters were monitored via unrestrained whole-body
      plethysmography. Conscious male Sprague-Dawley rats received an intravenous
      injection of vehicle or the peripherally-restricted MU-OR antagonist, naloxone
      methiodide (NLXmi), and then three successive injections of morphine (1 mg/kg)
      given 30 min apart. The first injection of morphine in vehicle-treated rats
      elicited an array of ventilatory excitant (i.e., increases in frequency of
      breathing, minute volume, respiratory drive, peak inspiratory and expiratory
      flows, accompanied by decreases in inspiratory time and end inspiratory pause)
      and inhibitory (i.e., a decrease in tidal volume and an increase in expiratory
      time) responses. Subsequent injections of morphine elicited progressively and
      substantially smaller responses. The pattern of ventilatory responses elicited by
      the first injection of morphine was substantially affected by pretreatment with
      NLXmi whereas NLXmi minimally affected the development of tolerance to these
      responses. Low-dose morphine elicits an array of ventilatory excitant and
      depressant effects in conscious rats that are subject to the development of
      tolerance. Many of these initial actions of morphine appear to involve activation
      of peripheral MU-ORs whereas the development of tolerance to these responses does
      not.

PMID- 24900949
TI  - Nitric Oxide Synthase is Necessary for Normal Urogenital Development.
AB  - INTRODUCTION: Neuronal nitric oxide synthase (NOS-I) is significantly decreased
      with Cavernous Nerve (CN) injury in Erectile Dysfunction (ED) models. Increased
      apoptosis and collagen deposition accompany decreased NOS/CN injury, however
      these changes are typically attributed to the altered signaling of other factors,
      and a contribution of NOS in maintenance of urogenital structures has not
      previously been examined. Morphological changes in the corpora cavernosa occur at
      the same time as decreased NOS, suggesting a potential connection between
      decreased/inhibited NOS and morphological changes associated with ED. In this
      study we propose that NOS impacts urogenital morphology during development and
      will examine this hypothesis by NOS inhibition with L-NAME. METHODS: Primary
      outcomes were H&E, western and TUNEL to determine if penis, prostate and bladder
      morphology were altered with L-NAME treatment of Postnatal day 4 (P4) Sprague
      Dawley rats for 8 days. Tissue weight and immunohistochemical analysis for NOS
      were performed. Secondary evaluation of NOS-I regulation by Sonic Hedgehog (SHH)
      was examined by SHH inhibition in the pelvic ganglia (PG) and NOS-I protein was
      quantified by western in the PG/CN and penis. Nos abundance was quantified by RT
      PCR during urogenital development and after CN injury. RESULTS: Apoptosis
      increased and penis, prostate and bladder morphology were altered with L-NAME.
      NOS inhibition decreased bladder weight 25%. SHH inhibition decreased NOS-I 35%
      in the PG/CN and 47% in the penis. Nos-III expression spiked within the first two
      weeks after birth in the penis but remained abundant in the adult. In the
      prostate, Nos-III was abundant immediately after birth and declined steadily with
      age. Nos-I expression in the PG/CN decreased sharply with CN injury and returned
      to baseline by 7 days. CONCLUSIONS: NOS is required for normal urogenital
      development. Since NOS is decreased with ED, it may contribute to the abnormal
      morphology observed in ED patients and animal models.

PMID- 24900950
TI  - Allergen-Specific Immunotherapy in Asthma.
AB  - Current asthma therapies can effectively control symptoms and the on-going
      inflammatory process; however, they do not affect the underlying, dysregulated
      immune response. Thus, they are limited to blunting the progression of the
      disease, which relapses on ceasing the treatment. Allergen-specific immunotherapy
      (AIT) is the only etiology-based treatment capable of disease modification.
      Recent evidence provided a plausible explanation for its multiple mechanisms
      inducing both rapid desensitization and long-term allergen-specific immune
      tolerance, as well as the suppression of allergic inflammation in the affected
      tissues. Although the current guideline documents give both subcutaneous (SCIT)
      and sublingual (SLIT) immunotherapy a conditional recommendation in allergic
      asthma due to the moderate and low quality of evidence, respectively, a growing
      body of evidence from double-blind, placebo-controlled studies shows that both
      SLIT and SCIT are effective in reducing symptom scores and medication use,
      improving quality of life, and inducing favorable changes in specific immunologic
      markers. Due to the very limited evidence from head-to-head comparative studies
      and variability of the end-point used in different studies, it is currently not
      possible to assess superiority of either route of vaccine administration.

PMID- 24900951
TI  - A Possible Effect of Concentrated Oolong Tea Causing Transient Ischemic Attack
      Like Symptoms.
AB  - AIMS: Tea (green, oolong, and black) is the second most widely consumed beverage
      worldwide, second only to water. Aside from a few reported adverse effects, tea,
      particularly green tea, appears to be beneficial for human health. In the case
      described herein, a male experienced several transient ischemic attack-like
      symptoms immediately following the consumption of a cup of high quality oolong
      tea. A thorough medical evaluation uncovered no evidence of such an attack and
      leads to the suggestion of a heretofore unreported response to oolong tea.
      PRESENTATION OF CASE: A 72-year old male with hypertension and atrial
      fibrillation, who takes valsartan/hydrochlorothiazide to control hypertension and
      warfarin to reduce the risk of thrombosis and thromboembolism, presented at the
      emergency room of a local hospital describing several transient ischemic attack
      like symptoms immediately after consuming a cup of oolong tea. His symptoms
      included presyncope, disequilibrium, bilateral hand parathesias, mild dysphasia,
      and visual problems (but apparently not presbyopia or amaurosis fugax), all of
      which had disappeared in approximately two hours after drinking the tea. (Mild
      presyncope was previously noted by the patient when ingesting a strong green
      tea.) No unusual features emerged from his physical examination, and his blood
      work was unremarkable except for elevation of his partial thromboplastin time (39
      sec) and prothrombin time (22.5 sec), giving an international reference of 2.0,
      all consistent with the effects of warfarin. A battery of tests by the emergency
      room physician, a cardiologist, and a neurologist, e.g. electrocardiogram, brain
      computerized tomography, 2-dimensional transthoracic echocardiogram, brain
      magnetic resonance imaging, with and without 20 ml Gadolinium, and a magnetic
      resonance angiogram, confirmed the earlier diagnosis of atrial fibrillation but
      disclosed no additional malfunction in his heart. His brain showed no evidence of
      a prior hemorrhage, and his carotid arteries were clear. METHODOLOGY AND RESULTS:
      Analysis of the oolong tea by high performance liquid chromatography and mass
      spectrometry identified the major catechins and two methylxanthines, caffeine and
      theophylline, as well as other constituents, but there was no evidence of any
      extraneous chemicals that could lead to the symptoms. CONCLUSION: In view of the
      rapid onset of symptoms after the consumption of oolong tea, bilateral as opposed
      to unilateral parathesis, and the absence of any evidence of a hemorrhage or the
      presence of impurities in the tea, we suggest that the transient ischemic attack
      like symptoms could possibly be attributable to one or more components of the
      oolong tea and was not an atypical magnetic resonance imaging-negative transient
      ischemic attack.

PMID- 24900952
TI  - Antitumor effects of saffron-derived carotenoids in prostate cancer cell models.
AB  - Crocus sativus L. extracts (saffron) are rich in carotenoids. Preclinical studies
      have shown that dietary intake of carotenoids has antitumor effects suggesting
      their potential preventive and/or therapeutic roles. We have recently reported
      that saffron (SE) and crocin (CR) exhibit anticancer activity by promoting cell
      cycle arrest in prostate cancer (PCa) cells. It has also been demonstrated that
      crocetin esters are produced after SE gastrointestinal digestion by CR
      hydrolysis. The aim of the present report was to investigate if SE, crocetin
      (CCT), and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3
      and 22rv1) which were xenografted in male nude mice treated by oral gavage with
      SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher
      when compared to CR and SE and treatments reverted the epithelial-mesenchymal
      transdifferentiation (EMT) as attested by the significant reduction of N-cadherin
      and beta-catenin expression and the increased expression of E-cadherin.
      Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through
      the downmodulation of metalloproteinase and urokinase expression/activity
      suggesting that these agents may affect metastatic processes. Our findings
      suggest that CR and CCT may be dietary phytochemicals with potential antitumor
      effects in biologically aggressive PCa cells. 

PMID- 24900953
TI  - Visualization and treatment of subclinical actinic keratoses with topical
      imiquimod 5% cream: an observational study.
AB  - BACKGROUND: Imiquimod 5% is licensed for the treatment of external genital warts,
      superficial basal cell carcinoma, and actinic keratosis (AK) and is being used
      experimentally in various other dermato-oncological conditions. OBJECTIVE: This
      observational study shall show that nonmelanoma skin cancer can be detected at
      its earliest subclinical stage by its reaction with imiquimod and can be cleared
      by finishing the course of treatment. MATERIAL AND METHODS: In this single arm
      trial 15 patients with chronically sun-exposed skin who had no clinical evidence
      of AK were treated with 5% imiquimod cream on the face or scalp for 4 weeks three
      times per week. RESULTS: During treatment, all patients developed multiple areas
      with mild to moderate inflammatory skin reactions, such as erythema, induration,
      and scaling. Biopsies obtained from 12 patients prior to treatment revealed no
      malignancies. However, in cases with more pronounced inflammation during
      treatment, targeted biopsies indicated very early malignant alterations.
      CONCLUSION: Topical imiquimod treatment of chronically sun-exposed skin without
      overt clinical signs of AK is able to detect subclinical actinic keratoses (SAK)
      and to completely clear the lesions, even before they can be clinically diagnosed
      as AK. In such patients, imiquimod might be able to prevent the evolution of SCC.

PMID- 24900955
TI  - Validation of reference genes for normalization gene expression in reverse
      transcription quantitative PCR in human normal thyroid and goiter tissue.
AB  - Reverse transcription quantitative polymerase chain reaction (RT-qPCR) has been
      recognized as the most accurate method for quantifying mRNA transcripts, but
      normalization of samples is a prerequisite for correct data interpretation. So,
      this study aimed to evaluate the most stable reference gene for RT-qPCR in human
      normal thyroid and goiter tissues. Beta-actin (ACTB); glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH); succinate dehydrogenase, subunit A, flavoprotein (Fp)
      (SDHA); hypoxanthine phosphoribosyltransferase I (HPRTI); tyrosine 3
      monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide
      (YWHAZ); and beta-2-microglobulin (B2M) were evaluated in 14 thyroid tissue
      samples (7 normal and 7 goiter tissues) by RT-qPCR. The mean Cq and the maximum
      fold change (MFC) and NormFinder software were used to assess the stability of
      the genes. As a result, ACTB gene was more stable than GAPDH, SDHA, HPRTI, YWHAZ,
      and B2M. In conclusion, ACTB could be used to normalize RT-qPCR data in normal
      thyroid and goiter tissues.

PMID- 24900956
TI  - Translational neuroimaging of the mood and anxiety disorders.

PMID- 24900954
TI  - Mitochondrial dysfunctions in neurodegenerative diseases: relevance to
      Alzheimer's disease.
AB  - Mitochondrial dysfunctions are supposed to be responsible for many
      neurodegenerative diseases dominating in Alzheimer's disease (AD), Parkinson's
      disease (PD), and Huntington's disease (HD). A growing body of evidence suggests
      that defects in mitochondrial metabolism and particularly of electron transport
      chain may play a role in pathogenesis of AD. Structurally and functionally
      damaged mitochondria do not produce sufficient ATP and are more prominent in
      producing proapoptotic factors and reactive oxygen species (ROS), and this can be
      an early stage of several mitochondrial disorders, including neurodegenerative
      diseases. Mitochondrial dysfunctions may be caused by both mutations in
      mitochondrial or nuclear DNA that code mitochondrial components and by
      environmental causes. In the following review, common aspects of mitochondrial
      impairment concerned about neurodegenerative diseases are summarized including
      ROS production, impaired mitochondrial dynamics, and apoptosis. Also, damaged
      function of electron transport chain complexes and interactions between
      pathological proteins and mitochondria are described for AD particularly and
      marginally for PD and HD. 

PMID- 24900957
TI  - Adhesion of pancreatic cancer cells in a liver-microvasculature mimicking
      coculture correlates with their propensity to form liver-specific metastasis in
      vivo.
AB  - Organ-specific characteristic of endothelial cells (ECs) is crucial for specific
      adhesion of cancer cells to ECs, which is a key factor in the formation of organ
      specific metastasis. In this study, we developed a coculture of TMNK-1
      (immortalized liver sinusoidal ECs) with 10T1/2 (resembling hepatic stellate
      cells) to augment organ-specific characteristic of TMNK-1 and investigated
      adhesion of two pancreatic cancer cells (MIA-PaCa-2 and BxPC-3) in the culture.
      MIA-PaCa-2 and BxPC-3 adhesion in TMNK-1+10T1/ 2|coating culture (TMNK-1
      monolayer over 10T1/2 layer on collagen coated surface) were similar. However, in
      TMNK-1+10T1/ 2|gel (coculture on collagen gel surface), MIA-PaCa-2 adhesion was
      significantly higher than BxPC-3, which was congruent with the reported higher
      propensity of MIA-PaCa-2 than BxPC-3 to form liver metastasis in vivo. Notably,
      as compared to BxPC-3, MIA-PaCa-2 adhesion was lower and similar in TMNK-1 only
      culture on the collagen coated and gel surfaces, respectively. Investigation of
      the adhesion in the representative human umbilical vein ECs (HUVECs) cultures and
      upon blocking of surface molecules of ECs revealed that MIA-PaCa-2 adhesion was
      strongly dependent on the organ-specific upregulated characteristics of TMNK-1 in
      TMNK-1+10T1/ 2|gel culture. Therefore, the developed coculture would be a
      potential assay for screening novel drugs to inhibit the liver-microvasculature
      specific adhesion of cancer cells.

PMID- 24900958
TI  - Endothelium-independent vasorelaxant effects of hydroalcoholic extract from
      Nigella sativa seed in rat aorta: the roles of Ca2+ and K+ channels.
AB  - OBJECTIVE: The aim of this study was to elucidate the mechanism(s) responsible
      for the vasorelaxant effect of Nigella sativa (N. sativa). METHODS: The activity
      of different concentrations of N. sativa extract was evaluated on contractile
      responses of isolated aorta to KCl and phenylephrine (PE). RESULTS: The extract
      (2-14 mg/mL) induced a concentration dependent relaxation both in endothelium
      intact and endothelium-denuded aortic rings precontracted by PE (10(-6) M) and
      KCl (6 * 10(-2) M). Extract reduced PE- and KCl-induced contractions in presence
      of cumulative concentrations of calcium (10(-5)-10(-2) M) significantly. L-NAME
      and indomethacin had no effect on vasorelaxation effect of extract in PE-induced
      contraction. Diltiazem and heparin reduced significantly this vasorelaxation at a
      concentration of 14 mg/mL of extract; however, N. sativa-induced relaxation was
      not affected by ruthenium red. Tetraethylammonium chloride reduced the extract
      induced relaxation in concentrations of 2-6 mg/mL of extract significantly but
      glibenclamide reduced this relaxative effect in all concentrations of extract.
      CONCLUSIONS: The inhibitory effect of N. sativa seed extract on the contraction
      induced by PE and KCl was endothelium-independent. This relaxation was mediated
      mainly through the inhibition of Ca(2+) and KATP channels and also intracellular
      calcium release.

PMID- 24900959
TI  - The role of arterioles and the microcirculation in the development of vasospasm
      after aneurysmal SAH.
AB  - Cerebral vasospasm of the major cerebral arteries, which is characterized by
      angiographic narrowing of those vessels, had been recognized as a main
      contributor to delayed cerebral ischemia (DCI) in subarachnoid hemorrhage (SAH)
      patients. However, the CONSCIOUS-1 trial revealed that clazosentan could not
      improve mortality or clinical outcome in spite of successful reduction of
      relative risk in angiographic vasospasm. This result indicates that the
      pathophysiology underlying DCI is multifactorial and that other
      pathophysiological factors, which are independent of angiographic vasospasm, can
      contribute to the outcome. Recent studies have focused on microcirculatory
      disturbance, such as microthrombosis and arteriolar constriction, as a factor
      affecting cerebral ischemia after SAH. Reports detecting microthrombosis and
      arteriolar constriction will be reviewed, and the role of the microcirculation on
      cerebral ischemia during vasospasm after SAH will be discussed. 

PMID- 24900960
TI  - Gastric antiulcerogenic and hypokinetic activities of Terminalia fagifolia Mart.
      & Zucc. (Combretaceae).
AB  - The acute toxicity, the antioxidant activity, and the pharmacological activity on
      the gastrointestinal tract of rodents of the ethanolic extract (TFEE) from the
      bark of Terminalia fagifolia Mart. & Zucc. (Combretaceae) and of its aqueous
      (TFAqF), hydroalcoholic (TFHAF), and hexanic (TFHEXF) partition fractions have
      been evaluated. TFEE presented low acute toxicity, antioxidant, and
      antiulcerogenic activity against ethanol-induced ulcers, which was partially
      blocked by pretreatment with L-NAME and indomethacin. It reduced the total
      acidity and raised the pH of gastric secretion. Additionally, TFEE delayed
      gastric emptying and slightly inhibited the small intestinal transit and also
      presented a weakly antidiarrheal activity. The antiulcerogenic and antioxidant
      activity were also detected in TFAqF and TFHAF but not in TFHEXF. The
      antisecretory and gastroprotective activity of TFEE partially involve the nitric
      oxide and prostaglandin participation. Nevertheless, TFEE, TFAqF, and TFHAF
      drastically reduced the mucus layer adhered to the gastric wall of rats treated
      with ethanol or indomethacin. Complementary studies are required in order to
      clarify the paradox of the presence of a gastroprotector activity in this plant
      that, at the same time, reduces the mucus layer adhered to the gastric wall. 

PMID- 24900961
TI  - Tobacco use among university students of Jazan Region: gender differences and
      associated factors.
AB  - OBJECTIVES: The main objectives of this study were to estimate the prevalence of
      tobacco use and behavioral patterns among undergraduate students at higher
      education institutions in the Jazan Region of Saudi Arabia during the 2011-2012
      academic year and to investigate factors that contribute to tobacco use by
      gender. METHODS: A cross-sectional study of 4100 undergraduate students was
      conducted. An anonymous self-administered questionnaire was used to collect
      information on the extent and pattern of tobacco consumption and factors
      associated with tobacco use. RESULTS: Current smokers accounted for 16.8% (95%
      CI: 15.6-18.1) of the population sampled; 25.6% (95% CI: 23.8-27.5) of males were
      current smokers, whereas only 4.6% (95% CI: 3.6-5.8) of females were current
      smokers (P = 0.000). Multivariate analysis revealed that the most important
      variables explaining tobacco use among study participants were the use of khat
      (OR = 14.05; P = 0.000), smoking status of friends (OR = 2.25; P = 0.000), and
      substance use by friends (OR = 1.81; P = 0.001). CONCLUSIONS: The results
      demonstrated that khat use was the main predictor for smoking in Jazan for both
      males and females. Interventions should be designed to reduce the use of tobacco
      among university students.

PMID- 24900963
TI  - Inter- and intrarater reliability of modified lateral scapular slide test in
      healthy athletic men.
AB  - OBJECTIVE: The reliability of lateral scapular slide test (LSST) at 90 degrees of
      abduction is controversial; therefore, in order to achieve more reliability it
      may be necessary to make changes in this particular position. METHODS: Modified
      lateral scapular slide test (MLSST) was done on thirty male basketball players
      with two examiners in one session and for the retest with one examiner in the
      next week. The test was done in 7 positions: arm relaxed at the side (P1), 90
      degrees of abduction (P2), 90 degrees of scaption without having a weight in
      hands (P3), 90 degrees of scaption with having 3 different weights (1, 2, and 4
      kg) in hands (P4, P5, and P6, resp.), and 180 degrees of scaption without having
      a weight in hands (P7). RESULTS: In P1 and P6, the ICC scores indicated the
      highest level of intrarater reliability. In P2, the ICC scores showed a fair
      level of intrarater reliability, as the minimum reliability. The maximum and
      minimum interrater reliability were P1 and P4, respectively. CONCLUSION: Scaption
      with loading, as a functional position in the overhead athletes, is a reliable
      positioning and may be replaced with the third position of the traditional LSST.

PMID- 24900962
TI  - Microsurgical techniques used to construct the vascularized and neurotized tissue
      engineered bone.
AB  - The lack of vascularization in the tissue engineered bone results in poor
      survival and ossification. Tissue engineered bone can be wrapped in the soft
      tissue flaps which are rich in blood supply to complete the vascularization in
      vivo by microsurgical technique, and the surface of the bone graft can be invaded
      with new vascular network. The intrinsic vascularization can be induced via a
      blood vessel or an arteriovenous loop located centrally in the bone graft by
      microsurgical technique. The peripheral nerve especially peptidergic nerve has
      effect on the bone regeneration. The peptidergic nerve can be used to construct
      the neurotized tissue engineered bone by implanting the nerve fiber into the
      center of bone graft. Thus, constructing a highly vascularized and neurotized
      tissue engineered bone according with the theory of biomimetics has become a
      useful method for repairing the large bone defect. Many researchers have used the
      microsurgical techniques to enhance the vascularization and neurotization of
      tissue engineered bone and to get a better osteogenesis effect. This review aims
      to summarize the microsurgical techniques mostly used to construct the
      vascularized and neurotized tissue engineered bone. 

PMID- 24900964
TI  - Systemic approach to identify serum microRNAs as potential biomarkers for acute
      myocardial infarction.
AB  - BACKGROUND: Recent studies have revealed the role of microRNAs (miRNAs) in a
      variety of biological and pathological processes, including acute myocardial
      infarction (AMI). We hypothesized that ST-segment elevation myocardial infarction
      (STEMI) may be associated with an alteration of miRNAs and that circulating
      miRNAs may be used as diagnostic markers for STEMI. METHODS: Expression levels of
      270 serum miRNAs were analyzed in 8 STEMI patients and 8 matched healthy controls
      to identify miRNAs differentially expressed in the sera of patients with AMI. The
      differentially expressed miRNAs were evaluated in a separate cohort of 62
      subjects, including 31 STEMI patients and 31 normal controls. RESULTS: The
      initial profiling study identified 12 upregulated and 13 downregulated serum
      miRNAs in the AMI samples. A subsequent validation study confirmed that serum miR
      486-3p and miR-150-3p were upregulated while miR-126-3p, miR-26a-5p, and miR-191
      5p were significantly downregulated in the sera of patients with AMI. Ratios
      between the level of upregulated and downregulated miRNAs were also significantly
      different in those with AMI. Receiver operator characteristics curve analysis
      using the expression ratio of miR-486-3p and miR-191-5p showed an area under the
      curve of 0.863. CONCLUSION: Our results suggest that serum miRNAs may be used as
      potential diagnostic biomarkers for STEMI.

PMID- 24900965
TI  - Nonsteroidal anti-inflammatory drugs and prostatic diseases.
AB  - Prostatic diseases are characterized by increased activity of cytokines, growth
      factors, and cyclooxygenases- (COX-) 1 and 2. Activation of COX-1 and COX-2
      results in increased levels of prostaglandins and the induction of angiogenic,
      antiapoptotic and inflammatory processes. Inhibition of COX enzymes by members of
      the widely used nonsteroidal anti-inflammatory drug (NSAID) class of drugs
      decreases prostaglandin production, and exerts a variety of anti-inflammatory,
      antipyretic, and antinociceptive effects. While numerous in vitro, in vivo, and
      clinical studies have shown that NSAIDs inhibit the risk and progression of
      prostatic diseases, the relationship between NSAIDs and such diseases remains
      controversial. Here we review the literature in this area, critically analyzing
      the benefits and caveats associated with the use of NSAIDs in the treatment of
      prostatic diseases. 

PMID- 24900966
TI  - Computational study to determine when to initiate and alternate therapy in HIV
      infection.
AB  - HIV is a widespread viral infection without cure. Drug treatment has transformed
      HIV disease into a treatable long-term infection. However, the appearance of
      mutations within the viral genome reduces the susceptibility of HIV to drugs.
      Therefore, a key goal is to extend the time until patients exhibit resistance to
      all existing drugs. Current HIV treatment guidelines seem poorly supported as
      practitioners have not achieved a consensus on the optimal time to initiate and
      to switch antiretroviral treatments. We contribute to this discussion with
      predictions derived from a mathematical model of HIV dynamics. Our results
      indicate that early therapy initiation (within 2 years postinfection) is critical
      to delay AIDS progression. For patients who have not received any therapy during
      the first 3 years postinfection, switch in response to virological failure may
      outperform proactive switching strategies. In case that proactive switching is
      opted, the switching time between therapies should not be larger than 100 days.
      Further clinical trials are needed to either confirm or falsify these
      predictions. 

PMID- 24900967
TI  - Glutaric acid-mediated apoptosis in primary striatal neurons.
AB  - Glutaric acid (GA) has been implicated in the mechanism of neurodegeneration in
      glutaric aciduria type I. In the present study, the potential cytotoxic effects
      of GA (0.1~50 mM for 24~96 h) were examined in cultured primary rat striatal
      neurons. Results showed increase in the number of cells labeled by annexin-V or
      with apoptotic features shown by Hoechst/PI staining and transmission electron
      microscopy (TEM) and upregulation of the expression of mRNA as well as the active
      protein fragments caspase 3, suggesting involvement of the caspase 3-dependent
      apoptotic pathway in GA-induced striatal neuronal death. This effect was in part
      suppressed by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 but not
      the alpha -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist 6
      cyano-7-nitroquinoxalone-2,3-dione (CNQX). Thus, GA may trigger neuronal damage
      partially through apoptotic pathway and via activation of NMDA receptors in
      cultured primary striatal neurons.

PMID- 24900968
TI  - Comprehensive detection, grading, and growth behavior evaluation of subthreshold
      and low intensity photocoagulation lesions by optical coherence tomographic and
      infrared image analysis.
AB  - PURPOSE: To correlate the long-term clinical effect of photocoagulation lesions
      after 6 months, as measured by their retinal damage size, to exposure parameters.
      We used optical coherence tomographic (OCT)-based lesion classes in order to
      detect and assess clinically invisible and mild lesions. METHODS: In this
      prospective study, 488 photocoagulation lesions were imaged in 20 patients. We
      varied irradiation diameters (100/300 um), exposure-times (20-200 ms), and power.
      Intensities were classified in OCT images after one hour, and we evaluated OCT
      and infrared (IR) images over six months after exposure. RESULTS: For six
      consecutive OCT-based lesion classes, the following parameters increased with the
      class: ophthalmoscopic, OCT and IR visibility rate, fundus and OCT diameter, and
      IR area, but not irradiation power. OCT diameters correlated with exposure-time,
      irradiation diameter, and OCT class. OCT classes discriminated the largest
      bandwidth of OCT diameters. CONCLUSION: OCT classes represent objective and valid
      endpoints of photocoagulation intensity even for "subthreshold" intensities. They
      are suitable to calculate the treated retinal area. As the area is critical for
      treatment efficacy, OCT classes are useful to define treatment intensity,
      calculate necessary lesion numbers, and universally categorize lesions in
      clinical studies.

PMID- 24900969
TI  - Phytochemical evaluation, antimicrobial activity, and determination of bioactive
      components from leaves of Aegle marmelos.
AB  - The therapeutic value of Aegle marmelos Correa (Rutaceae), commonly known as
      ''Bael," has been recognized as a component of traditional medication for the
      treatment of various human ailments. The plant, though, being highly explored,
      still lacks sufficient evidences for the best variety possessing the highest
      degree of medicinal values. The present study is focused on phytochemical
      screening of aqueous and methanolic leaf extracts of 18 varieties/accessions of
      A. marmelos. The crude extracts of A. marmelos revealed the presence of several
      biologically active phytochemicals with the highest quantity of alkaloids,
      flavonoids, and phenols in Pant Aparna variety. The antibacterial efficacy was
      investigated against pathogenic bacterial strains and the highest inhibitory
      activity of aqueous extract was obtained against S. epidermidis, whereas
      methanolic extract was found to be most potent against S. aureus at 40 mg/mL
      concentration. However, in aqueous : ethanol, the best results were observed
      against E. aerogenes followed by K. pneumonia and S. epidermidis. The MIC of
      aqueous and methanol extract of Aegle marmelos ranged from 10 mg/mL to 40 mg/mL
      whereas in aqueous : ethanol it ranged between 40 mg/mL and 160 mg/mL. The GC-MS
      analysis revealed the presence of many bioactive compounds such as flavonoids,
      alcohols, aldehydes, aromatic compounds, fatty acid methyl esters, terpenoids,
      phenolics, and steroids that can be postulated for antibacterial activity.

PMID- 24900970
TI  - Tanshinone IIA induces apoptosis in human oral cancer KB cells through a
      mitochondria-dependent pathway.
AB  - Tanshinone IIA (Tan IIA), an active phytochemical in the dried root of Salvia
      miltiorrhiza Bunge, has shown an antiproliferative activity on various human
      cancer cell lines including nasopharyngeal carcinoma cells. However, the effects
      of Tan IIA on human oral cancer cells are still unknown. This study aimed to
      investigate the antiproliferative effects of Tan IIA on human oral cancer KB
      cells and explored the possible underlying mechanism. Treatment of KB cells with
      Tan IIA suppressed cell proliferation/viability and induced cell death in a dose
      dependent manner through sulforhodamine B colorimetric assay. Observation of cell
      morphology revealed the involvement of apoptosis in the Tan IIA-induced growth
      inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M
      phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane
      potential observed by flow cytometry and the expression of activated caspases
      with the cleaved poly (ADP-ribose) polymerase under immunoblotting analysis
      indicated that Tan IIA-induced apoptosis in KB cells was mediated through the
      mitochondria-dependent caspase pathway. These observations suggested that Tan IIA
      could be a potential anticancer agent for oral cancer.

PMID- 24900971
TI  - Meta-analysis of low density lipoprotein receptor (LDLR) rs2228671 polymorphism
      and coronary heart disease.
AB  - Low density lipoprotein receptor (LDLR) can regulate cholesterol metabolism by
      removing the excess low density lipoprotein cholesterol (LDL-C) in blood. Since
      cholesterol metabolism is often disrupted in coronary heart disease (CHD), LDLR
      as a candidate gene of CHD has been intensively studied. The goal of our study is
      to evaluate the overall contribution of LDLR rs2228671 polymorphism to the risk
      of CHD by combining the genotyping data from multiple case-control studies. Our
      meta-analysis is involved with 8 case-control studies among 7588 cases and 9711
      controls to test the association between LDLR rs2228671 polymorphism and CHD. In
      addition, we performed a case-control study of LDLR rs2228671 polymorphism with
      the risk of CHD in Chinese population. Our meta-analysis showed that rs2228671-T
      allele was significantly associated with a reduced risk of CHD (P = 0.0005, odds
      ratio (OR) = 0.83, and 95% confidence interval (95% CI) = 0.75-0.92). However,
      rs2228671-T allele frequency was rare (1%) and was not associated with CHD in Han
      Chinese (P = 0.49), suggesting an ethnic difference of LDLR rs2228671
      polymorphism. Meta-analysis has established rs2228671 as a protective factor of
      CHD in Europeans. The lack of association in Chinese reflects an ethnic
      difference of this genetic variant between Chinese and European populations.

PMID- 24900972
TI  - Can melatonin help us in radiation oncology treatments?
AB  - Nowadays, radiotherapy has become an integral part of the treatment regimen in
      various malignancies for curative or palliative purposes. Ionizing radiation
      interacts with biological systems to produce free radicals, which attack various
      cellular components. Radioprotectors act as prophylactic agents that are
      administered to shield normal cells and tissues from the harmful effects of
      radiation. Melatonin has been shown to be both a direct free radical scavenger
      and an indirect antioxidant by stimulating antioxidant enzymes and suppressing
      prooxidative enzymes activity. In addition to its antioxidant property, there
      have also been reports implicating antiapoptotic function for melatonin in normal
      cells. Furthermore, through its antitumor and radiosensitizing properties,
      treatment with melatonin may prevent tumor progression. Therefore, addition of
      melatonin to radiation therapy could lower the damage inflicted to the normal
      tissue, leading to a more efficient tumor control by use of higher doses of
      irradiation during radiotherapy. Thus, it seems that, in the future, melatonin
      may improve the therapeutic gain in radiation oncology treatments. 

PMID- 24900973
TI  - Time-intensity curve parameters in rectal cancer measured using endorectal
      ultrasonography with sterile coupling gels filling the rectum: correlations with
      tumor angiogenesis and clinicopathological features.
AB  - The primary aim of this study was to investigate the relationship between
      contrast-enhanced ultrasonography (CEUS) imaging parameters and
      clinicopathological features of rectal carcinoma and assess their potential as
      new radiological prognostic predictors. A total of 66 rectal carcinoma patients
      were analyzed with the time-intensity curve of CEUS. The parameter arrival time
      (AT), time to peak enhancement (TTP), wash-in time (WIT), enhanced intensity
      (EI), and ascending slope (AS) were measured. Microvessel density (MVD) was
      evaluated by immunohistochemical staining of surgical specimens. All findings
      were analysed prospectively and correlated with tumor staging, histological
      grading, and MVD. The mean values of AT, TTP, WIT, EI, and AS value of the rectal
      carcinoma were 10.84 +/- 3.28 s, 20.61 +/- 5.52 s, 9.78 +/- 2.83 s, 28.68 +/-
      4.67 dB, and 3.20 +/- 1.10, respectively. A positive linear correlation was found
      between the EI and MVD in rectal carcinoma (r = 0.295, P = 0.016), and there was
      a significant difference for EI among histological grading (r = -0.264, P =
      0.007). EI decreased as T stage increased with a trend of association noted (P =
      0.096). EI of contrast enhanced endorectal ultrasonography provides noninvasive
      biomarker of tumor angiogenesis in rectal cancer. CEUS data have the potential to
      predict patient prognosis.

PMID- 24900974
TI  - Morphohistological features of pancreatic stump are the main determinant of
      pancreatic fistula after pancreatoduodenectomy.
AB  - INTRODUCTION: Pancreatic surgery is challenging and associated with high
      morbidity, mainly represented by postoperative pancreatic fistula (POPF) and its
      further consequences. Identification of risk factors for POPF is essential for
      proper postoperative management. AIM OF THE STUDY: Evaluation of the role of
      morphological and histological features of pancreatic stump, other than main
      pancreatic duct diameter and glandular texture, in POPF occurrence after
      pancreaticoduodenectomy. PATIENTS AND METHODS: Between March 2011 and April 2013,
      we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively
      recorded morphological features of pancreatic stump and collected data about
      postoperative morbidity. Our dedicated pathologist designed a score to quantify
      fibrosis and inflammation of pancreatic tissue. RESULTS: Overall morbidity was
      59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF
      were 15,8%. Male sex (P = 0.009), BMI >= 25 (P = 0.002), prolonged surgery (P =
      0.001), soft pancreatic texture (P < 0.001), small pancreatic duct (P < 0.001),
      pancreatic duct decentralization on stump anteroposterior axis, especially if
      close to the posterior margin (P = 0.031), large stump area (P = 0.001), and
      extended stump mobilization (P = 0.001) were related to higher POPF rate. Our
      fibrosis-and-inflammation score is strongly associated with POPF (P = 0.001).
      DISCUSSION AND CONCLUSIONS: Pancreatic stump features evaluation, including
      histology, can help the surgeon in fitting postoperative management to patient
      individual risk after pancreaticoduodenectomy.

PMID- 24900975
TI  - Shared mechanisms of neurodegeneration in Alzheimer's disease and Parkinson's
      disease.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) have markedly different
      clinical and pathological features, but these two diseases are the most common
      neurodegenerative disorders. Previous studies have showed that there are common
      mechanisms in AD and PD. Several genetic studies have revealed mutations in genes
      associated with the risk of AD and PD. Circumstantial evidences have shown that
      dysregulation of brain iron homeostasis leads to abnormal iron accumulation and
      results in AD as well as PD. alpha -Synuclein and tau take part in the mechanisms
      of these diseases by oxidative stress and mitochondrial dysfunction. Some studies
      indicated that the loss of LC noradrenergic neurons may occur early in the
      progression of AD and PD. Nicotinic acetylcholine receptors (nAChRs) are members
      of the Cys-loop superfamily of pentameric ligand-gated ion channels; some
      evidence showed that nicotinic receptors may be associated with AD and PD. These
      experimental and clinical studies may provide a scientific foundation for common
      shared mechanisms in AD and PD. 

PMID- 24900976
TI  - Antimicrobial and controlled release studies of a novel nystatin conjugated iron
      oxide nanocomposite.
AB  - Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of
      antifungal activity. In the present study, we prepared a nystatin nanocomposite
      (Nyst-CS-MNP) by loading nystatin (Nyst) on chitosan (CS) coated magnetic
      nanoparticles (MNPs). The magnetic nanocomposites were characterized by X-ray
      powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR),
      thermogravimetry analysis (TGA), vibrating sample magnetometer (VSM), and
      scanning electron microscopy (SEM). The XRD results showed that the MNPs and
      nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS
      on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The
      Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9%
      loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS
      MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from
      the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial
      activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated
      using an agar diffusion method and showed enhanced antifungal activity against
      Candida albicans. In this manner, this study introduces a novel nanocomposite
      that can decrease fungus activity on-demand for numerous medical applications.

PMID- 24900977
TI  - Implementation study of patient-ready syringes containing 25 mg/mL methotrexate
      solution for use in treating ectopic pregnancy.
AB  - BACKGROUND: Ectopic pregnancy (EP) is a significant cause of morbidity and
      mortality during the first trimester of pregnancy. Small unruptured tubal
      pregnancies can be treated medically with a single dose of methotrexate (MTX).
      OBJECTIVE: The aim of this study was to evaluate the stability of a 25 mg/mL
      solution of MTX to devise a secure delivery circuit for the preparation and use
      of this medication in the management of EP. METHOD: MTX solutions were packaged
      in polypropylene syringes, stored over an 84-day period, and protected from light
      either at +2 to +8 degrees C or at 23 degrees C. We assessed the physical and
      chemical stability of the solutions at various time points over the storage
      period. A pharmaceutical delivery circuit was implemented that involved the batch
      preparation of MTX syringes. RESULTS: We show that 25 mg/mL MTX solutions remain
      stable over an 84-day period under the storage conditions tested. Standard doses
      were prepared, ranging from 50 mg to 100 mg. The results of this study suggest
      that MTX syringes can be prepared in advance by the pharmacy, ready to be
      dispensed at any time that a diagnosis of EP is made. CONCLUSION: The high
      stability of a 25 mg/mL MTX solution in polypropylene syringes makes it possible
      to implement a flexible and cost-effective delivery circuit for ready-to-use
      preparations of this drug, providing 24-hour access and preventing treatment
      delays.

PMID- 24900978
TI  - Tract-based spatial statistics: application to mild cognitive impairment.
AB  - RATIONALE AND OBJECTIVES: The primary objective of the current investigation was
      to characterize white matter integrity in different subtypes of mild cognitive
      impairment (MCI) using tract-based spatial statistics of diffusion tensor
      imaging. MATERIALS AND METHODS: The study participants were divided into 4 groups
      of 30 subjects each as follows: cognitively healthy controls, amnestic MCI,
      dysexecutive MCI, and Alzheimer's disease (AD). All subjects underwent a
      comprehensive neuropsychological assessment, apolipoprotein E genotyping, and 3
      tesla MRI. The diffusion tensor was reconstructed and then analyzed using tract
      based spatial statistics. The changes in brain white matter tracts were also
      examined according to the apolipoprotein E epsilon 4 status. RESULTS: Compared
      with controls, amnestic MCI patients showed significant differences in the
      cerebral white matter, where changes were consistently detectable in the frontal
      and parietal lobes. We found a moderate impact of the apolipoprotein E epsilon 4
      status on the extent of white matter disruption in the amnestic MCI group.
      Patients with AD exhibited similar but more extensive alterations, while no
      significant changes were observed in dysexecutive MCI patients. CONCLUSION: The
      results from this study indicate that amnestic MCI is the most likely precursor
      to AD as both conditions share significant white matter damage. By contrast,
      dysexecutive MCI seems to be characterized by a distinct pathogenesis.

PMID- 24900979
TI  - Radiosensitization effect of nedaplatin on nasopharyngeal carcinoma cells in
      different status of Epstein-Barr virus infection.
AB  - This study aims to evaluate the radiosensitization effect of nedaplatin on
      nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV)
      status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were
      treated with 0-100 MUg/mL nedaplatin, and inhibitory effects on cell viability
      and IC50 were calculated by MTS assay. We assessed changes in radiosensitivity of
      cells by MTS and colony formation assays, and detected the apoptosis index and
      changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused
      significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent
      manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50
      values of 34.32 and 63.69 MUg/mL, respectively. Compared with radiation alone,
      nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly
      increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin
      radiosensitized human NPC cells CNE-2 and C666, with a significantly greater
      effect on the former. The mechanisms of radiosensitization include induction of
      apoptosis and enhancement of cell cycle arrest in G2/M phase.

PMID- 24900980
TI  - Demographic characteristics, nicotine dependence, and motivation to quit as
      possible determinants of smoking behaviors and acceptability of shocking warnings
      in Italy.
AB  - INTRODUCTION: This paper presents the final results of a cross-sectional study
      started in 2010. It compares the perceived efficacy of different types of tobacco
      health warning (texts versus shocking pictures) to quit or reduce tobacco use.
      METHODS: The study conducted between 2010 and 2012 in Italy enrolled adults
      smokers. Administering a questionnaire demographic data, smokers behaviors were
      collected. Showing text and graphic warnings (the corpse of a smoker, diseased
      lungs, etc.) the most perceived efficacy to reduce tobacco consumption or to
      encourage was quit. RESULTS: 666 subjects were interviewed; 6% of responders
      referred that they stopped smoking at least one month due to the textual
      warnings. The 81% of the smokers perceived that the warnings with shocking
      pictures are more effective in reducing/quitting tobacco consumption than text
      only warnings. The younger group (<45 years), who are more motivated to quit
      (Mondor's score >= 12), and females showed a higher effectiveness of shocking
      warnings to reduce tobacco consumption of, 76%, 78%, and 43%, respectively with P
      < 0.05. CONCLUSIONS: This study suggests that pictorial warnings on cigarette
      packages are more likely to be noticed and rated as effective by Italian smokers.
      Female and younger smokers appear to be more involved by shock images. The
      jarring warnings also appear to be supporting those who want to quit smoking.
      This type of supportive information in Italy may become increasingly important
      for helping smokers to change their behavior.

PMID- 24900981
TI  - Correlation of altered expression of the autophagy marker LC3B with poor
      prognosis in astrocytoma.
AB  - Glioblastoma multiforme is one of the most serious malignant brain tumors and is
      characterized by resistance to chemotherapy and radiation therapy. Recent studies
      suggest that autophagy may play an important role not only in the regulation of
      cancer development and progression but also in determining the response of cancer
      cells to anticancer therapy. The purpose of the present study was to assess the
      relationship between protein expressions of two autophagy markers, LC3B and
      Beclin-1, with clinical parameters in astrocytoma patients. Furthermore, the
      expression of CD133, a marker of the cancer stem-like cells, in astrocytoma
      patients was also investigated. A total of 106 thin-section slides were
      retrospectively collected from astrocytoma patients. LC3B, but not Beclin-1,
      protein expression was found to significantly correlate with resistance to
      radiation- or chemotherapy. In addition, high intensity of LC3B staining was
      predictive of poor prognosis. Furthermore, survival time of patients with high
      level expression in both CD133 and LC3B was significantly shorter than those with
      weak expression in both CD133 and LC3B. These results suggest that astrocytoma
      cancer stem-like cells together with enhanced autophagy may cause resistance to
      radiation therapy/chemotherapy and that targeting the cancer stem-like cell in
      astrocytoma may offer a viable therapeutic approach. 

PMID- 24900982
TI  - c-Kit expression, angiogenesis, and grading in canine mast cell tumour: a unique
      model to study c-Kit driven human malignancies.
AB  - Canine cutaneous mast cell tumour (CMCT) is a c-Kit driven tumour sharing similar
      c-Kit aberrations found in human gastrointestinal stromal tumour. CMCT is
      classified into three forms: well- (G1), intermediately (G2) (more benign
      diseases), and poorly (G3) differentiated (malignant) forms. We assess a
      correlation between c-Kit status, grading, and angiogenesis in CMCTs to explore
      their potential significance in humans. C-Kit receptor (c-KitR) expression,
      microvascular density (MVD), and mast cell granulated and degranulated status
      density (MCGD and MCDD, resp.) were analyzed in 97 CMCTs, by means of
      histochemistry, immunohistochemistry double staining, and image analysis system.
      Data showed that predominantly diffuse cytoplasmic- and predominantly focal
      paranuclear- (Golgi-like) c-Kit protein (PDC-c-Kit and PFP-c-Kit, resp.)
      expression correlate with high MVD, G3 histopathological grade, and MCDD.
      Moreover, predominant cell membrane-c-KitR (PCM-c-KitR) expression status
      correlates with low MVD, G1-G2 histopathological grade, and MCGD. These findings
      underline the key role of c-Kit in the biopathology of canine MCTs, indicating a
      link between aberrant c-Kit expression, increased angiogenesis, and higher
      histopathological grade. CMCT seems to be a model to study contributions of c-Kit
      activated MCs in tumour angiogenesis and to evaluate the inhibition of MCs
      activation by means of c-Kit tyrosine kinase inhibitors, currently translated in
      humans. 

PMID- 24900983
TI  - Electrospun polyhydroxybutyrate and poly(L-lactide-co-epsilon-caprolactone)
      composites as nanofibrous scaffolds.
AB  - Electrospinning can produce nanofibrous scaffolds that mimic the architecture of
      the extracellular matrix and support cell attachment for tissue engineering
      applications. In this study, fibrous membranes of polyhydroxybutyrate (PHB) with
      various loadings of poly(L-lactide-co-epsilon-caprolactone) (PLCL) were
      successfully prepared by electrospinning. In comparison to PLCL scaffolds, PLCL
      blends with PHB exhibited more irregular fibre diameter distributions and higher
      average fibre diameters but there were no significant differences in pore size.
      PLCL/PHB scaffolds were more hydrophilic (<120 degrees ) with significantly
      reduced tensile strength (ca. 1 MPa) compared to PLCL scaffolds (150.9 +/- 2.8
      degrees  and 5.8 +/- 0.5 MPa). Increasing PLCL loading in PHB/PLCL scaffolds
      significantly increased the extension at break, (4-6-fold). PLCL/PHB scaffolds
      supported greater adhesion and proliferation of olfactory ensheathing cells
      (OECs) than those exhibiting asynchronous growth on culture plates. Mitochondrial
      activity of cells cultivated on the electrospun blended membranes was enhanced
      compared to those grown on PLCL and PHB scaffolds (212, 179, and 153%, resp.).
      Analysis showed that PLCL/PHB nanofibrous membranes promoted cell cycle
      progression and reduced the onset of necrosis. Thus, electrospun PLCL/PHB
      composites promoted adhesion and proliferation of OECs when compared to their
      individual PLCL and PHB components suggesting potential in the repair and
      engineering of nerve tissue.

PMID- 24900984
TI  - In silico design of BACE1 inhibitor for Alzheimer's disease by traditional
      Chinese medicine.
AB  - The beta-site APP cleaving enzyme 1 (BACE1) is an important target for causing
      Alzheimer's disease (AD), due to the brain deposition peptide amyloid beta
      (Abeta) require cleavages of amyloid precursor protein (APP) by BACE1 and gamma
      secretase, but treatments of AD still have side effect in recent therapy. This
      study utilizes the world largest traditional Chinese medicine (TCM) database and
      database screening to provide potential BACE1 inhibited compound. Molecular
      dynamics (MD) simulation was carried out to observe the dynamics structure after
      ligand binding. We found that Triptofordin B1 has less toxicity than pyrimidine
      analogue, which has more potent binding affinity with BACE1. For trajectory
      analysis, all conformations are tending to be stable during 5000 ps simulation
      time. In dynamic protein validation, the residues of binding region are still
      stable after MD simulation. For snapshot comparison, we found that Triptofordin
      B1 could reduce the binding cavity; the results reveal that Triptofordin B1 could
      bind to BACE1 and better than control, which could be used as potential lead drug
      to design novel BACE1 inhibitor for AD therapy.

PMID- 24900985
TI  - Integration of residue attributes for sequence diversity characterization of
      terpenoid enzymes.
AB  - Progress in the "omics" fields such as genomics, transcriptomics, proteomics, and
      metabolomics has engendered a need for innovative analytical techniques to derive
      meaningful information from the ever increasing molecular data. KNApSAcK
      motorcycle DB is a popular database for enzymes related to secondary metabolic
      pathways in plants. One of the challenges in analyses of protein sequence data in
      such repositories is the standard notation of sequences as strings of
      alphabetical characters. This has created lack of a natural underlying metric
      that eases amenability to computation. In view of this requirement, we applied
      novel integration of selected biochemical and physical attributes of amino acids
      derived from the amino acid index and quantified in numerical scale, to examine
      diversity of peptide sequences of terpenoid synthases accumulated in KNApSAcK
      motorcycle DB. We initially generated a reduced amino acid index table. This is a
      set of biochemical and physical properties obtained by random forest feature
      selection of important indices from the amino acid index. Principal component
      analysis was then applied for characterization of enzymes involved in synthesis
      of terpenoids. The variance explained was increased by incorporation of residue
      attributes for analyses. 

PMID- 24900986
TI  - Experience of 1166 thyroidectomy without use of prophylactic antibiotic.
AB  - BACKGROUND: Although the procedure requires a small surgical incision and a short
      duration, incision infection rate is very low in thyroidectomy; however, doctors
      still have misgivings about infection events. AIM: We retrospectively analyzed
      the prevention of incision infection without perioperative use of antibacterial
      medications following thyroidectomy. MATERIALS AND METHODS: 1166 patients of
      thyroidectomy were not administered perioperative antibiotics. Unilateral total
      lobectomy or partial thyroidectomy was performed in 68.0% patients with single
      side nodular goiter or thyroid adenoma. Bilateral partial thyroidectomy was
      performed in 25.5% patients with nodular goiter or Graves' disease. The mean time
      of operation was 80.6 +/- 4.87 (range: 25-390) min. RESULTS: Resuturing was
      performed in two patients of secondary hemorrhage from residual thyroid following
      bilateral partial thyroidectomy. Temporally recurrent nerve paralysis was
      reported following right-side total lobectomy and left-side subtotal lobectomy in
      a nodular goiter patient. One case had suppurative infection in neck incision 5
      days after bilateral partial thyroidectomy. CONCLUSIONS: Thyroidectomy, which is
      a clean incision, involves a small incision, short duration, and minor
      hemorrhage. If the operation is performed under strict conditions of sterility
      and hemostasis, antibacterial medications may not be required to prevent incision
      infection, which reduces cost and discourages the excessive use of antibiotics.

PMID- 24900987
TI  - Multidisciplinary management of hepatocellular carcinoma in clinical practice.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) patients require different treatment
      strategies according to disease extension, liver function, and patient's fitness.
      We evaluated HCC multidisciplinary management in clinical practice. METHODS:
      Consecutive patients were followed and treated with tailored medical,
      locoregional, and surgical treatments, according to disease stage and patient's
      fitness (age, Cumulative Illness Rating Scale (CIRS)). Activity, efficacy, and
      safety were evaluated. RESULTS: Thirty-eight patients were evaluated: median age,
      74; elderly 92%; CIRS secondary 28 (74%); Child-Pugh A 20 (53%), B 11 (29%); and
      Barcelona Clinic Liver Cancer (BCLC) 0 2 (5%), A 9 (24%), B 10 (26%), C 13 (34%),
      and D 4 (11%). Overall survival (OS) was 30 months. At 9 months median follow-up,
      among 25 unresectable HCC, OS was 10 months; BCLC B-D unfit for sorafenib showed
      OS 3 months. Ten patients (40%) received sorafenib: Child-Pugh A 5 (50%) and B 5
      (50%) and disease control rate 89%, progression-free survival 7 months, and OS 9
      months. G3-4 toxicities: anorexia, hypertransaminaemia, hyperbilirubinemia, and
      hypercreatininemia. Limiting toxicity syndromes were 40%, all multiple sites.
      CONCLUSION: HCC patients require multidisciplinary clinical management to
      properly select tailored treatments according to disease stage, fitness, and
      liver function. Patients suitable for sorafenib should be carefully selected,
      monitored for individual safety, and prevalently characterized by limiting
      toxicity syndromes multiple sites.

PMID- 24900989
TI  - Physical therapy in wound healing, edema, and urinary incontinence.

PMID- 24900988
TI  - ATF4- and CHOP-dependent induction of FGF21 through endoplasmic reticulum stress.
AB  - Fibroblast growth factor 21 (FGF21) is an important endogenous regulator involved
      in the regulation of glucose and lipid metabolism. FGF21 expression is strongly
      induced in animal and human subjects with metabolic diseases, but little is known
      about the molecular mechanism. Endoplasmic reticulum (ER) stress plays an
      essential role in metabolic homeostasis and is observed in numerous pathological
      processes, including type 2 diabetes, overweight, nonalcoholic fatty liver
      disease (NAFLD). In this study, we investigate the correlation between the
      expression of FGF21 and ER stress. We demonstrated that TG-induced ER stress
      directly regulated the expression and secretion of FGF21 in a dose- and time
      dependent manner. FGF21 is the target gene for activating transcription factor 4
      (ATF4) and CCAAT enhancer binding protein homologous protein (CHOP). Suppression
      of CHOP impaired the transcriptional activation of FGF21 by TG-induced ER stress
      in CHOP-/- mouse primary hepatocytes (MPH), and overexpression of ATF4 and CHOP
      resulted in FGF21 promoter activation to initiate the transcriptional programme.
      In mRNA stability assay, we indicated that ER stress increased the half-life of
      mRNA of FGF21 significantly. In conclusion, FGF21 expression is regulated by ER
      stress via ATF- and CHOP-dependent transcriptional mechanism and
      posttranscriptional mechanism, respectively. 

PMID- 24900990
TI  - No evidence for an association of vitamin D deficiency and migraine: a systematic
      review of the literature.
AB  - Vitamin D deficiency is associated with a number of human disorders, including
      cardiovascular disease, cancer, diabetes, frailty, and infections. Since an
      association between vitamin D and migraine has also been recently speculated, we
      performed an electronic search on Medline, Scopus, and Web of Science using the
      keywords "migraine" and "vitamin D," "25OH-D" "cholecalciferol,"
      "ergocalciferol," with no language or date restriction. The electronic search
      allowed identifying seven studies (3 observational, 2 cross-sectional, and 2 case
      reports). The two case reports, including four women, showed favourable effects
      of vitamin D supplementation on migraine severity, but these studies were small
      and not placebo controlled. As regards the three observational studies, vitamin D
      deficiency was observed in 13.2 to 14.8% of migraine patients, and these rates do
      not differ from those reported in the general population (i.e., vitamin D
      deficiency between 22 and 42%). The results of the two cross-sectional studies
      are even more controversial, since no association was found between vitamin D
      status and migraine in both trials. In conclusion, the current evidence suggests
      that the association between migraine and vitamin D lacks reliable scientific
      support.

PMID- 24900991
TI  - Risks of decreased renal function and increased albuminuria for glycemic status
      and metabolic syndrome components: Taichung Community Health study.
AB  - BACKGROUND: The objective of this study was to assess the association of glycemic
      status and decreased renal function as determined by estimated glomerular
      filtration rate (eGFR) and albuminuria in an adult Taiwanese metropolitan
      population. METHODS: We did a cross-sectional survey in a representative sample
      of 2,350 Taiwanese adults aged 40 years and over living in a metropolitan city in
      Taiwan from 2004 to 2005. Glycemic status was classified as normal glycemia,
      hyperglycemia, and type 2 diabetes (T2D). Renal function was assessed with eGFR
      using modified Modification of Diet in Renal Disease Study equation for Chinese.
      Albuminuria was determined by the urinary albumin-creatinine ratio. Decreased
      renal function was defined as eGFR <60 mL/min/1.73 m(2) and albuminuria as the
      albumin-creatinine ratio >30 mg g(-1) creatinine. RESULTS: 593 (25.23%) had
      hyperglycemia and 287 (12.21%) had T2D. As glycemia level increased, the
      prevalence of albuminuria and decreased eGFR increased. After adjustment, T2D was
      associated with an OR of 2.93 (95% CI: 2.11-4.07) for albuminuria, and an OR of
      2.05 (95% CI: 1.18-3.58) for decreased eGFR. CONCLUSIONS: In a representative
      sample from a metropolitan city in Taiwan, T2D was associated with albuminuria
      and decreased eGFR.

PMID- 24900992
TI  - Serum leptin levels in pemphigus: a case control study.
AB  - BACKGROUND: Pemphigus is an autoimmune blistering disease mediated by
      autoantibodies directed against keratinocyte adhesion molecules. Leptin, an
      adipocyte-derived hormone, plays a role in immune responses and promotes
      autoimmunity. OBJECTIVES: This study was conducted to determine whether serum
      leptin levels are altered in pemphigus patients and whether there is any
      correlation between leptin levels and the severity of disease. METHODS: This
      study included 47 newly diagnosed patients with pemphigus and 43 age- and sex
      matched healthy controls. Clinical characteristics and pemphigus area and
      activity score (PAAS) were assessed. Serum leptin levels (ng/mL) were measured by
      a commercial enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients did not
      differ significantly in serum leptin levels from healthy controls (median
      (range): 10.8 (0.1-110) ng/mL versus 12 (0.5-69.9) ng/mL and P = 0.53). There was
      no significant association between serum leptin concentrations and severity of
      disease measured by PAAS (r s = 0.06, P = 0.70). CONCLUSION: The results suggest
      that pemphigus does not have a direct influence on serum leptin levels and the
      pathogenesis of pemphigus seems to be not dependent on the connection with
      adipose tissue.

PMID- 24900993
TI  - Evidence for bladder urothelial pathophysiology in functional bladder disorders.
AB  - Understanding of the role of urothelium in regulating bladder function is
      continuing to evolve. While the urothelium is thought to function primarily as a
      barrier for preventing injurious substances and microorganisms from gaining
      access to bladder stroma and upper urinary tract, studies indicate it may also
      function in cell signaling events relating to voiding function. This review
      highlights urothelial abnormalities in bladder pain syndrome/interstitial
      cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic
      idiopathic overactive bladder (OAB). These bladder conditions are typified by
      lower urinary tract symptoms including urinary frequency, urgency, urgency
      incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and
      cells from affected clinical subjects and asymptomatic controls have been
      compared for expression of proteins and mRNA. Animal models have also been used
      to probe urothelial responses to injuries of the urothelium, urethra, or central
      nervous system, and transgenic techniques are being used to test specific
      urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to
      share some common pathophysiology including increased purinergic, TRPV1, and
      muscarinic signaling, increased urothelial permeability, and aberrant urothelial
      differentiation. One challenge is to determine which of several abnormally
      regulated signaling pathways is most important for mediating bladder dysfunction
      in these syndromes, with a goal of treating these conditions by targeting
      specific pathophysiology. 

PMID- 24900994
TI  - Breath ketone testing: a new biomarker for diagnosis and therapeutic monitoring
      of diabetic ketosis.
AB  - BACKGROUND: Acetone, beta -hydroxybutyric acid, and acetoacetic acid are three
      types of ketone body that may be found in the breath, blood, and urine. Detecting
      altered concentrations of ketones in the breath, blood, and urine is crucial for
      the diagnosis and treatment of diabetic ketosis. The aim of this study was to
      evaluate the advantages of different detection methods for ketones, and to
      establish whether detection of the concentration of ketones in the breath is an
      effective and practical technique. METHODS: We measured the concentrations of
      acetone in the breath using gas chromatography-mass spectrometry and beta 
      hydroxybutyrate in fingertip blood collected from 99 patients with diabetes
      assigned to groups 1 (-), 2 (+/-), 3 (+), 4 (++), or 5 (+++) according to urinary
      ketone concentrations. RESULTS: There were strong relationships between fasting
      blood glucose, age, and diabetic ketosis. Exhaled acetone concentration
      significantly correlated with concentrations of fasting blood glucose, ketones in
      the blood and urine, LDL-C, creatinine, and blood urea nitrogen. CONCLUSIONS:
      Breath testing for ketones has a high sensitivity and specificity and appears to
      be a noninvasive, convenient, and repeatable method for the diagnosis and
      therapeutic monitoring of diabetic ketosis.

PMID- 24900995
TI  - New progress in angiogenesis therapy of cardiovascular disease by ultrasound
      targeted microbubble destruction.
AB  - Angiogenesis plays a vital part in the pathogenesis and treatment of
      cardiovascular disease and has become one of the hotspots that are being
      discussed in the past decades. At present, the promising angiogenesis therapies
      are gene therapy and stem cell therapy. Besides, a series of studies have shown
      that the ultrasound targeted microbubble destruction (UTMD) was a novel gene
      delivery system, due to its advantages of noninvasiveness, low immunogenicity and
      toxicity, repeatability and temporal and spatial target specificity; UTMD has
      also been used for angiogenesis therapy of cardiovascular disease. In this
      review, we mainly discuss the combination of UTMD and gene therapy or stem cell
      therapy which is applied in angiogenesis therapy in recent researches, and
      outline the future challenges and good prospects of these approaches. 

PMID- 24900996
TI  - Effects of synergistic massage and physical exercise on the expression of
      angiogenic markers in rat tendons.
AB  - Physical exercise and massage are regarded as key factors in regulating tendon
      structure. However, information on the mechanism through which massage influences
      the structure and biology of a tendon is scarce. In this study, we attempted to
      define the impact of these two activities on rat tendons by using morphological
      and molecular techniques, determining the expression of VEGF-A, FGF-2, and CD34
      in the tendons of rats subjected to 10 weeks of physical exercise (running) with
      massage of varied duration. The group of rats that was trained and massaged
      during the entire study was characterized by the highest expression of these
      markers, compared to the rats subjected to massage before training and to the
      control group subjected to physical exercises only. The greatest significant
      differences, compared to the control, were noted in the expression of all the
      studied markers at mRNA level, and in the case of VEGF-A, at protein level, in
      the third and fifth weeks of the experiment. The results of this study could
      point to the synergistic impact of simultaneous massage and physical exercise on
      the expression of angiogenesis markers in rat tendons. 

PMID- 24900997
TI  - Nucleobase-based barbiturates: their protective effect against DNA damage induced
      by bleomycin-iron, antioxidant, and lymphocyte transformation assay.
AB  - A number of nucleobase-based barbiturates have been synthesized by combination of
      nucleic acid bases and heterocyclic amines and barbituric acid derivatives
      through green and efficient multicomponent route and one pot reaction. This
      approach was accomplished efficiently using aqueous medium to give the
      corresponding products in high yield. The newly synthesized compounds were
      characterized by spectral analysis (FT-IR, (1)H NMR, (13)C NMR, HMBC, and UV
      spectroscopy) and elemental analysis. Representative of all synthesized compounds
      was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and
      Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest
      lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant
      activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3 -TBA manifested
      the best protective effect against DNA damage induced by bleomycin. 

PMID- 24900999
TI  - Topography prediction of helical transmembrane proteins by a new modification of
      the sliding window method.
AB  - Protein functions are specified by its three-dimensional structure, which is
      usually obtained by X-ray crystallography. Due to difficulty of handling membrane
      proteins experimentally to date the structure has only been determined for a very
      limited part of membrane proteins (<4%). Nevertheless, investigation of structure
      and functions of membrane proteins is important for medicine and pharmacology
      and, therefore, is of significant interest. Methods of computer modeling based on
      the data on the primary protein structure or the symbolic amino acid sequence
      have become an actual alternative to the experimental method of X-ray
      crystallography for investigating the structure of membrane proteins. Here we
      presented the results of the study of 35 transmembrane proteins, mainly GPCRs,
      using the novel method of cascade averaging of hydrophobicity function within the
      limits of a sliding window. The proposed method allowed revealing 139
      transmembrane domains out of 140 (or 99.3%) identified by other methods. Also 236
      transmembrane domain boundary positions out of 280 (or 84%) were predicted
      correctly by the proposed method with deviation from the predictions made by
      other methods that does not exceed the detection error of this method. 

PMID- 24901001
TI  - Pycnogenol ameliorates depression-like behavior in repeated corticosterone
      induced depression mice model.
AB  - Oxidative stress is considered to be a mechanism of major depression. Pycnogenol
      (PYC) is a natural plant extract from the bark of Pinus pinaster Aiton and has
      potent antioxidant activities. We studied the ameliorative effect of PYC on
      depression-like behavior in chronic corticosterone- (CORT-) treated mice for 20
      days. After the end of the CORT treatment period, PYC (0.2 mg/mL) was orally
      administered in normal drinking water. Depression-like behavior was investigated
      by the forced swimming test. Immobility time was significantly longer by CORT
      exposure. When the CORT-treated mice were supplemented with PYC, immobility time
      was significantly shortened. Our results indicate that orally administered PYC
      may serve to reduce CORT-induced stress by radical scavenging activity.

PMID- 24900998
TI  - Power of proteomics in linking oxidative stress and female infertility.
AB  - Endometriosis, PCOS, and unexplained infertility are currently the most common
      diseases rendering large numbers of women infertile worldwide. Oxidative stress,
      due to its deleterious effects on proteins and nucleic acids, is postulated to be
      the one of the important mechanistic pathways in differential expression of
      proteins and in these diseases. The emerging field of proteomics has allowed
      identification of proteins involved in cell cycle, as antioxidants, extracellular
      matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female
      infertility related diseases. The aim of this paper is to assess the association
      of oxidative stress and protein expression in the reproductive microenvironments
      such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as
      reproductive tissues and serum. The review also highlights the literature that
      proposes the use of the fertility related proteins as potential biomarkers for
      noninvasive and early diagnosis of the aforementioned diseases rather than
      utilizing the more invasive methods used currently. The review will highlight the
      power of proteomic profiles identified in infertility related disease conditions
      and their linkage with underlying oxidative stress. The power of proteomics will
      be reviewed with regard to eliciting molecular mechanisms for early detection and
      management of these infertility related conditions. 

PMID- 24901000
TI  - Chromatographic fingerprint analysis and effects of the medicinal plant species
      Mitracarpus frigidus on adult Schistosoma mansoni worms.
AB  - The aims of this work were to evaluate the in vitro and in vivo schistosomicidal
      properties of the methanolic extract of the aerial parts of Mitracarpus frigidus
      (MFM) and to determine its HPLC profile. For the in vitro experiment, four pairs
      of adult worms, obtained from infected mice, were exposed to different
      concentrations of MFM (100 to 400 MUg/mL) for 24 and 48 h and analyzed under an
      inverted microscope. For the in vivo experiment, mice were inoculated with
      cercariae and, 20 days after infection, MFM (100 and 300 mg/kg) was administered
      orally for the following 25 days. Mice were euthanized after 60 days. MFM showed
      in vitro schistosomicidal activity, exhibiting the opening of the gynaecophoral
      canal of some male schistosomes, the presence of contorted muscles, vesicles, and
      the darkening of the paired worms skin. In vivo experiments showed that MFM
      treatments significantly reduced total worm count, as praziquantel, showing a
      decrease in liver and spleen weight. Also, a significant reduction in granuloma
      density was observed. MFM treatment did not cause alterations in the liver
      function of either infected or noninfected mice. The HPLC chromatogram profile
      showed the presence of kaempferol-O-rutinoside, rutin, kaempferol, psychorubrin,
      and ursolic acid.

PMID- 24901002
TI  - New SPECT and PET radiopharmaceuticals for imaging cardiovascular disease.
AB  - Nuclear cardiology has experienced exponential growth within the past four
      decades with converging capacity to diagnose and influence management of a
      variety of cardiovascular diseases. Single photon emission computed tomography
      (SPECT) myocardial perfusion imaging (MPI) with technetium-99m radiotracers or
      thallium-201 has dominated the field; however new hardware and software designs
      that optimize image quality with reduced radiation exposure are fuelling a
      resurgence of interest at the preclinical and clinical levels to expand beyond
      MPI. Other imaging modalities including positron emission tomography (PET) and
      magnetic resonance imaging (MRI) continue to emerge as powerful players with an
      expanded capacity to diagnose a variety of cardiac conditions. At the forefront
      of this resurgence is the development of novel target vectors based on an
      enhanced understanding of the underlying pathophysiological process in the
      subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered
      to target a specific subcellular process has the capacity to improve diagnostic
      accuracy and deliver enhanced prognostic information to alter management. This
      paper, while not comprehensive, will review the recent advancements in
      radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis,
      atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry
      and preclinical and clinical development in addition to molecular imaging with
      emerging modalities such as cardiac MRI and PET-MR will be discussed. 

PMID- 24901003
TI  - O18Quant: a semiautomatic strategy for quantitative analysis of high-resolution
      16O/18O labeled data.
AB  - Proteolytic (18)O-labeling has been widely used in quantitative proteomics since
      it can uniformly label all peptides from different kinds of proteins. There have
      been multiple algorithms and tools developed over the last few years to analyze
      high-resolution proteolytic (16)O/(18)O labeled mass spectra. We have developed a
      software package, O18Quant, which addresses two major issues in the previously
      developed algorithms. First, O18Quant uses a robust linear model (RLM) for
      peptide-to-protein ratio estimation. RLM can minimize the effect of outliers
      instead of iteratively removing them which is a common practice in other
      approaches. Second, the existing algorithms lack applicable implementation. We
      address this by implementing O18Quant using C# under Microsoft.net framework and
      R. O18Quant automatically calculates the peptide/protein relative ratio and
      provides a friendly graphical user interface (GUI) which allows the user to
      manually validate the quantification results at scan, peptide, and protein
      levels. The intuitive GUI of O18Quant can greatly enhance the user's
      visualization and understanding of the data analysis. O18Quant can be downloaded
      for free as part of the software suite ProteomicsTools. 

PMID- 24901004
TI  - Alkylation of histidine residues of Bothrops jararacussu venom proteins and
      isolated phospholipases A2: a biotechnological tool to improve the production of
      antibodies.
AB  - Crude venom of Bothrops jararacussu and isolated phospholipases A2 (PLA2) of this
      toxin (BthTX-I and BthTX-II) were chemically modified (alkylation) by p
      bromophenacyl bromide (BPB) in order to study antibody production capacity in
      function of the structure-function relationship of these substances (crude venom
      and PLA2 native and alkylated). BthTX-II showed enzymatic activity, while BthTX-I
      did not. Alkylation reduced BthTX-II activity by 50% while this process abolished
      the catalytic and myotoxic activities of BthTX-I, while reducing its edema
      inducing activity by about 50%. Antibody production against the native and
      alkylated forms of BthTX-I and -II and the cross-reactivity of antibodies to
      native and alkylated toxins did not show any apparent differences and these
      observations were reinforced by surface plasmon resonance (SPR) data.
      Histopathological analysis of mouse gastrocnemius muscle sections after injection
      of PBS, BthTX-I, BthTX-II, or both myotoxins previously incubated with
      neutralizing antibody showed inhibition of the toxin-induced myotoxicity. These
      results reveal that the chemical modification of the phospholipases A2 (PLA2)
      diminished their toxicity but did not alter their antigenicity. This observation
      indicates that the modified PLA2 may provide a biotechnological tool to attenuate
      the toxicity of the crude venom, by improving the production of antibodies and
      decreasing the local toxic effects of this poisonous substance in animals used to
      produce antivenom. 

PMID- 24901006
TI  - Naturally occurring compounds elicit HIV-1 replication in chronically infected
      promonocytic cells.
AB  - Since antiretroviral therapy suppresses but does not eradicate HIV-1 infection,
      methods to purge viral reservoirs are required. Many strategies involve the
      reactivation of chronically HIV infected cells to induce the expression of
      integrated viral genome. In this study, five bioactive compounds, the plant
      derivatives 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), nordihydroguaiaretic
      acid (NDGA), and curcumin (Cur) and the synthetic stigmasterol analogs (22S,23S)
      22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3 beta -bromo-5
      alpha ,22,23-trihydroxystigmastan-6-one (compound 2), were evaluated for their
      ability to elicit HIV replication in promonocytic (U1) and lymphocytic (H9+) HIV
      1 chronically infected cells. The results revealed that natural compounds CDM,
      NDGA, and Cur were able to increase HIV-1 p24 antigen, determined by ELISA, only
      in latently infected promonocytic cells. CDM would reactivate HIV from latency by
      modulating the release of IL-6 and TNF- alpha , since the amount of both
      cytokines measured through ELISA significantly increased in U1 treated cells.
      Besides, NDGA increased ROS production, which might be related to the increase on
      p24 level observed in NDGA treated U1. These findings suggest that CDM, NDGA, and
      Cur might be candidates for further studies on latency-reversing therapeutics to
      eliminate latently HIV-1 reservoirs. 

PMID- 24901005
TI  - Bladder cancer and urothelial impairment: the role of TRPV1 as potential drug
      target.
AB  - Urothelium, in addition to its primary function of barrier, is now understood to
      act as a complex system of cell communication that exhibits specialized sensory
      properties in the regulation of physiological or pathological stimuli.
      Furthermore, it has been hypothesized that bladder inflammation and neoplastic
      cell growth, the two most representative pathological conditions of the lower
      urinary tract, may arise from a primary defective urothelial lining. Transient
      receptor potential vanilloid channel 1 (TRPV1), a receptor widely distributed in
      lower urinary tract structures and involved in the physiological micturition
      reflex, was described to have a pathophysiological role in inflammatory
      conditions and in the genesis and development of urothelial cancer. In our
      opinion new compounds, such as curcumin, the major component of turmeric Curcuma
      longa, reported to potentiate the effects of the chemotherapeutic agents used in
      the management of recurrent urothelial cancer in vitro and also identified as one
      of several compounds to own the vanillyl structure required to work like a TRPV1
      agonist, could be thought as complementary in the clinical management of both the
      recurrences and the inflammatory effects caused by the endoscopic resection or
      intravesical chemotherapy administration or could be combined with adjuvant
      agents to potentiate their antitumoral effect. 

PMID- 24901007
TI  - Association of Helicobacter pylori infection with glycemic control in patients
      with diabetes: a meta-analysis.
AB  - OBJECTIVE. To assess the association between Helicobacter pylori (HP) infection
      and glycemic control in patients with diabetes through a meta-analytic approach.
      RESEARCH DESIGN AND METHODS. Electronic literature searches were conducted for
      cross-sectional studies that examined the hemoglobin A1c (A1C) level by whether
      patients with diabetes were or were not carriers of HP. Mean differences in A1C
      between groups with and without HP infection were pooled with a random-effects
      model. RESULTS. Thirteen eligible studies were included in this meta-analysis.
      Overall, the HP carriers did not have significantly higher A1C levels compared
      with HP noncarriers (mean difference (95% CI), 0.19% (-0.18 to 0.46), P = 0.16).
      When the analysis was limited to studies targeting patients with type 1 diabetes,
      there was also no significant difference in A1C (0.69% (-0.31 to 1.68), P =
      0.18). CONCLUSIONS. There was insufficient evidence that HP infection worsened
      glycemic control in patients with diabetes.

PMID- 24901009
TI  - Involvement of the circadian rhythm and inflammatory cytokines in the
      pathogenesis of rheumatoid arthritis.
AB  - Among the symptoms of patients with rheumatoid arthritis (RA), joint stiffness is
      influenced by diurnal rhythm and reaches peak in the morning, which is a common
      complaint and reflects the circadian nature of disease manifestation. In
      addition, inflammatory cytokines, which reach peak secretion early in the morning
      are major players causing the morning stiffness. In this review, we explore the
      link between the circadian clock and inflammation, focusing on the interactions
      of various clock genes with the immune-pathways underlying the pathology of
      rheumatoid arthritis. 

PMID- 24901010
TI  - HLA associations and clinical implications in T-cell mediated drug
      hypersensitivity reactions: an updated review.
AB  - T-cell mediated drug hypersensitivity reactions may range from mild rash to
      severe fatal reactions. Among them, drug reaction with eosinophilia and systemic
      symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens
      Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life
      threatening severe cutaneous adverse reactions (SCARs). Recent advances in
      pharmacogenetic studies show strong genetic associations between human leukocyte
      antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review
      summarizes the literature on recent progresses in pharmacogenetic studies and
      clinical application of pharmacogenetic screening based on associations between
      SCARs and specific HLA alleles to avoid serious conditions associated with drug
      hypersensitivity. 

PMID- 24901011
TI  - The role of protein modifications of T-bet in cytokine production and
      differentiation of T helper cells.
AB  - T-Bet (T-box protein expressed in T cells, also called as TBX21) was originally
      cloned as a key transcription factor involved in the commitment of T helper (Th)
      cells to the Th1 lineage. T-Bet directly activates IFN-gamma gene transcription
      and enhances development of Th1 cells. T-Bet simultaneously modulates IL-2 and
      Th2 cytokines in an IFN-gamma-independent manner, resulting in an attenuation of
      Th2 cell development. Numerous studies have demonstrated that T-bet plays
      multiple roles in many subtypes of immune cells, including B cell, dendritic
      cells, natural killer (NK) cells, NK T cells, and innate lymphoid cells.
      Therefore, T-bet is crucial for the development and coordination of both innate
      and adaptive immune responses. To fulfill these multiple roles, T-bet undergoes
      several posttranslational protein modifications, such as phosphorylation at
      tyrosine, serine, and threonine residues, and ubiquitination at lysine residues,
      which affect lineage commitment during Th cell differentiation. This review
      presents a current overview of the progress made in understanding the roles of
      various types of T-bet protein modifications in the regulation of cytokine
      production during Th cell differentiation. 

PMID- 24901014
TI  - Quantitative Analysis of Uterine Action Potentials.

PMID- 24901012
TI  - The new insight into the role of antimicrobial proteins-alarmins in the
      immunopathogenesis of psoriasis.
AB  - The pathognesis of psoriasis still remains not fully elucidated. Recent advances
      favor the idea that interactions between innate and adaptive immune response
      drive inflammatory process in this disease. Innate antimicrobial peptides and
      proteins (AMPs) are diverse group of small molecules that provide the first line
      of defense against invading pathogens. In recent years, the novel functions of
      AMPs have been identified. There are three subclasses among AMPs that have gained
      the special interest as a potentially important player in the pathogenesis of
      psoriasis: cathelicidin, S100 proteins, and defensins. These AMPs have been shown
      to modulate and trigger host immune response in psoriasis acting as interplayer
      between innate and adaptive immune mechanisms. Overexpressed in psoriatic
      lesions, they prime immune cells for enhanced production of proinflammatory
      mediators and act as chemoattractant for leukocytes. Therefore, the novel term
      describing AMPs alarmins has been suggested. As multifunctional player in
      pathogenesis of psoriasis, AMPs may constitute potential target for therapeutic
      interventions. However, further investigations are required to establish the
      methods of downregulation of the aberrant proinflammatory functions of AMPs
      without increasing the risk of infections. 

PMID- 24901008
TI  - Chronic inflammation and cytokines in the tumor microenvironment.
AB  - Acute inflammation is a response to an alteration induced by a pathogen or a
      physical or chemical insult, which functions to eliminate the source of the
      damage and restore homeostasis to the affected tissue. However, chronic
      inflammation triggers cellular events that can promote malignant transformation
      of cells and carcinogenesis. Several inflammatory mediators, such as TNF-alpha,
      IL-6, TGF-beta, and IL-10, have been shown to participate in both the initiation
      and progression of cancer. In this review, we explore the role of these cytokines
      in important events of carcinogenesis, such as their capacity to generate
      reactive oxygen and nitrogen species, their potential mutagenic effect, and their
      involvement in mechanisms for epithelial mesenchymal transition, angiogenesis,
      and metastasis. Finally, we will provide an in-depth analysis of the
      participation of these cytokines in two types of cancer attributable to chronic
      inflammatory disease: colitis-associated colorectal cancer and
      cholangiocarcinoma.

PMID- 24901013
TI  - Unraveling natalizumab effects on deregulated miR-17 expression in CD4+ T cells
      of patients with relapsing-remitting multiple sclerosis.
AB  - MicroRNAs (miRNAs) are a family of noncoding RNAs that play critical roles in the
      posttranscriptional regulation of gene expression. Accumulating evidence supports
      their involvement in the pathogenesis of multiple sclerosis (MS). Here, we
      compare miR-17 expressions in CD4+ T cells from relapsing-remitting (RR) MS
      patients treated with natalizumab versus untreated patients. miR-17 was
      downregulated under natalizumab treatment and upregulated during relapse,
      therefore supporting a possible role of miR-17 in MS immunopathogenesis.
      Downregulation of miR-17 was associated with upregulation of PTEN, BIM, E2F1, and
      p21 target genes. In vitro miR-17 inhibition was associated with upregulation of
      the same targets and resulted in impaired CD4+ T cell activation and
      proliferation. We further describe deregulated TGFBR2 expression in untreated
      patients versus healthy volunteers (HVs) and confirm in vitro the link between
      miR-17 and TGFBR2 expressions. These findings support an effect of natalizumab on
      expression of specific miRNA and subsequent expression of genes involved in
      proliferation and control of the cell cycle.

PMID- 24901015
TI  - Clinical value of 99Tcm-MDP SPECT bone scintigraphy in the diagnosis of
      unilateral condylar hyperplasia.
AB  - PURPOSE: To investigate the clinical value of (99)Tc(m)-MDP SPECT for the
      diagnosis of unilateral condylar hyperplasia (UCH). METHODS: One hundred forty
      nine patients who underwent mandibular (99)Tc(m)-MDP SPECT between January 2009
      and December 2012 were studied, including 105 cases that were clinically
      suspected of UCH and 44 comparable cases without UCH as a control group. RESULTS:
      Increased bone activity was observed in the affected condyles for all UCH
      patients. In the UCH group, the relative percentage uptake on the affected side
      was 59% (SD +/- 4.3%), significantly higher than the 41% (SD +/- 4.1%) uptake on
      the contralateral side (P<0.001). Similarly, the condyle/skull ratio was
      significantly higher for the affected side (1.66 +/- 0.63) than for the
      contralateral side (1.34 +/- 0.34, P < 0.01. No significant difference was found
      in the control group between the left and right condyles. Values for the
      sensitivity (95%), specificity (61%), positive (84.4%) and negative (84.6%)
      predictive values, and accuracy (84.5%) for (99)Tc(m)-MDP SPECT in the diagnosis
      of UCH were calculated. However, for the hyperplastic condyle, no correlation was
      observed between the thickness of each cartilage layer and the relative uptake in
      the SPECT image. CONCLUSION: (99)Tc(m)-MDP SPECT is accurate for diagnosing UCH
      and can provide a reference for treatment options.

PMID- 24901016
TI  - A framework for sharing and integrating remote sensing and GIS models based on
      Web service.
AB  - Sharing and integrating Remote Sensing (RS) and Geographic Information
      System/Science (GIS) models are critical for developing practical application
      systems. Facilitating model sharing and model integration is a problem for model
      publishers and model users, respectively. To address this problem, a framework
      based on a Web service for sharing and integrating RS and GIS models is proposed
      in this paper. The fundamental idea of the framework is to publish heterogeneous
      RS and GIS models into standard Web services for sharing and interoperation and
      then to integrate the RS and GIS models using Web services. For the former, a
      "black box" and a visual method are employed to facilitate the publishing of the
      models as Web services. For the latter, model integration based on the geospatial
      workflow and semantic supported marching method is introduced. Under this
      framework, model sharing and integration is applied for developing the Pearl
      River Delta water environment monitoring system. The results show that the
      framework can facilitate model sharing and model integration for model publishers
      and model users. 

PMID- 24901017
TI  - The effects of Ramadan fasting on heart rate variability in healthy individuals:
      a prospective study.
AB  - OBJECTIVE: Ramadan fasting is one of the five fundamental rituals of Islam. Heart
      rate variability (HRV) is an independent predictor of increased mortality of
      patients with myocardial infarction and congestive heart failure. Although many
      patients in this region fast once a year, the effects of fasting on the HRV,
      which has a prognostic significance for patients with myocardial infarction and
      congestive heart failure, are not known. Therefore, the study on the effects of
      one month fast of HRV in healthy volunteers seems to be reasonable to address.
      METHODS: Our study is a prospective cohort study that includes a total of 40
      healthy volunteers with sinus rhythm between 19 and 40 years of age (16 female
      and 24 male). HRV was determined twice by ambulatory 24-hour Holter recordings at
      fasting in the middle of Ramadan and first week after Ramadan month. Mean values
      of continuous variables were compared by using the Student t-test or Mann-Whitney
      U test. Paired t-test or Wilcoxon test were used for comparison of variables
      between groups. RESULTS: When two groups compared, statistically significant
      differences were found in terms of RR (p=0.049), SDNNI (p=0.010), rMSSD
      (p=0.009), pNN50 (p=0.015), T power (p=0.009), LF (p=0.008), Lfnu (p=0.002), HF
      (p=0.022) and Hfnu (p=0.013) values. CONCLUSION: In our study, HRV parameters
      were found to be increased in Ramadan month, so we think that Ramadan fasting
      enhances the activity of the parasympathetic system.

PMID- 24901018
TI  - Assessment of right ventricular function by isovolumic contraction acceleration
      before and after percutaneous closure of atrial septal defects: a preliminary
      study.
AB  - OBJECTIVE: The main purpose of present study was to investigate the impact of
      percutaneous closure of atrial septal defect (ASD) on right ventricular (RV)
      systolic function assessed by tricuspid annular isovolumic myocardial
      acceleration (IVA) that is independent of preload and afterload changes. METHODS:
      A prospective cohort study was designed involving twenty five patients with
      secundum type ASD whom were successfully closed percutaneously between 2009 and
      2011. Standard transthoracic echocardiography and tissue Doppler imaging were
      performed in all patients 12 to 24 hours before and one month after closure.
      Paired t test was performed to determine the statistical significance of
      variables before and after closure. RESULTS: Significant decreases were observed
      in RV end-diastolic diameter, RV/left ventricular (LV) end-diastolic diameter
      ratio, right ventricular systolic myocardial velocity (Sm), right ventricular
      early myocardial velocity (Em) and right ventricular late myocardial velocity
      (Am) in the control echocardiography in the first month when compared with pre
      procedure values. While significant increase was observed after procedure in
      right ventricular IVA (3.4 +/- 1.3 m/sec2 vs. 4.2 +/- 1.8 m/sec2, p=0.001), no
      significant change was observed in right ventricular global performance index, in
      right ventricular Em/Am ratio and left ventricular ejection fraction. CONCLUSION:
      Percutaneous closure of ASD resulted in recovery of right ventricular function as
      early as 1 month after closure.

PMID- 24901019
TI  - Evaluation of left ventricular functions in patients with pseudoexfoliation
      syndrome using tissue Doppler echocardiography and its association with plasma
      BNP levels.
AB  - OBJECTIVE: Pseudoexfoliation syndrome (PES) is a systemic disorder that involves
      various visceral organs. In this observational cross-sectional study we aimed to
      investigate the left ventricular functions in patients with PES by using tissue
      Doppler imaging and correlations between B-type natriuretic peptide (BNP) levels
      and cardiac functions. METHODS: The study enrolled 22 patients with PES (9 male,
      41%), aged 57.0 +/- 8.8 years, and 23 control subjects (9 male, 39%), aged 52.8
      +/- 4.9 years. Patients with any cardiovascular disease were excluded. Fasting
      blood samples were taken and tissue Doppler imaging was performed at the mitral
      annulus with echocardiographic examination. The independent t and Mann-Whitney U
      tests were used. RESULTS: The Em velocities at the basal septum and lateral
      annulus were significantly lower in patients with PES showing decreased diastolic
      functions (7.6 +/- 2.0 versus 9.1 +/- 1.6 cm/s, p=0.01 and 9.3 +/- 3.5 versus
      11.5 +/- 3.1 cm/s, p=0.04 respectively). While global left ventricular systolic
      function assessed by ejection fraction was not significantly different between
      patients with PES and controls, the septum S-wave velocities of PES patients were
      lower (7.6 +/- 1.3 versus 8.5 +/- 1.2 cm/s, p=0.03). Total plasma BNP levels were
      significantly higher in PES patients (129.04 +/- 99.38 pg/mL versus 59.64 +/-
      53.69 pg/mL; p=0.005) and there was a negative correlation between plasma BNP
      concentration and mitral annulus average Em velocities (r=-0.554, p=0.009). E/Em
      ratio was also significantly higher in PES patients (7.85 +/- 2.01 versus 6.64 +/
      1.48, p=0.03). CONCLUSION: In this study we showed decreased left ventricular
      diastolic functions correlated with plasma BNP levels in PES patients. Although
      further studies needed, evaluation and follow-up of PES patients in terms of left
      ventricular functions will be useful.

PMID- 24901020
TI  - Assessment of the severity of aortic regurgitation with pulsed wave Doppler
      velocity profile in the descending aorta.
AB  - OBJECTIVE: The quantitative parameters which are used to assess the severity of
      aortic regurgitation (AR) provide the most accurate information whereas these
      parameters are difficult and time-consuming. The aim of this study was to get a
      practical parameter to use in daily practice for assessing the severity of aortic
      regurgitation. METHODS: The study was an observational cohort study on diagnostic
      accuracy of severity of aortic regurgitation. Thirty-seven patients with aortic
      regurgitation determined by quantitative parameters (18 patients with severe
      aortic regurgitation and 19 patients with moderate aortic regurgitation) were
      included in this study. Each patient's diastolic flow pattern in the descending
      aorta was examined by pulsed wave Doppler. Systolic and diastolic flow time
      velocity integral (TVI), TVI time, systolic and diastolic TVI ratio in the
      descending aorta were evaluated. In addition to these parameters, dP/dt, peak
      acceleration time and end-diastolic flow velocity in the diastolic flow were
      determined. We investigated whether there a significant difference between two
      groups or not. Receiver operating characteristic (ROC) analysis was used to
      determine the optimal cut-off values of echocardiographic parameters which were
      used to identify the severity of aortic regurgitation. RESULTS: The study
      population was composed of 16 female and 21 male patients. Their mean age was
      46.5 years. The mean diastolic flow TVI of patients who had moderate and severe
      aortic regurgitation was found 10.1 cm and 18.6 cm, respectively (p<0.001). In
      the ROC curve analysis, the values of diastolic flow TVI above 13.5 cm was found
      to have 83% sensitivity and 90% specifity to predict the severity of aortic
      regurgitation (AUC: 0.91, 95% CI 0.80-1.0, p<0.001). Also we investigated the
      other parameters like systolic flow TVI, the ratio of systolic and diastolic flow
      TVI, mean diastolic flow time, mean systolic flow time, the ratio of systolic and
      diastolic flow time, end-diastolic velocity, peak acceleration time, dP/dt values
      in evaluation of diastolic flow in the descending aorta. These parameters were
      found statistically significant in assessing the severity of aortic regurgitation
      but their statistical power was weak. CONCLUSION: TVI of diastolic flow which is
      measured with pulsed wave Doppler in descending aorta could be a practical
      parameter in assessing the severity of aortic regurgitation.

PMID- 24901021
TI  - Could decreased vitamin D levels be related with impaired cardiac autonomic
      functions in patients with chronic heart failure: an observational study.
AB  - OBJECTIVE: Vitamin D status has been implicated in the pathophysiology of heart
      failure (HF). The aim of this study was to investigate the association between
      vitamin D levels with heart rate variability and heart rate turbulence in
      patients with heart failure whom had ischemic and non-ischemic dilated
      cardiomyopathy. METHODS: Study designed as an observational cross-sectional
      study. Seventy-one patients [36 non-ischemic dilated cardiomyopathy (NIDCM), 35
      ischemic dilated cardiomyopathy (IDCM)] with chronic heart failure and 25 control
      subject were included. It was evaluated the association between 25 hydroxyvitamin
      D [25(OH)D] and calcitriol levels with heart rate variability time domain (SDNN,
      SDANN, RMSSD) and heart rate turbulence [turbulence onset (TO), turbulence slope
      (TS)] parameters. Statistical analysis was performed using Kruskal-Wallis test
      and ANOVA. RESULTS: Calcitriol levels in NIDCM patients with abnormal TO and TS
      were significantly lower than NIDCM patients with normal TO (17.1 +/- 11.3 vs.
      27.6 +/- 15.5 pg/mL, p=0.05) and TS (16.6 +/- 9.1 vs. 29.4 +/- 16.9 pg/mL,
      p=.018). There was a positive correlation between 25 (OH) D with heart rate
      variability parameters SDNN (r=0.368, p=0.027) and SDANN (r=0.360, p=0.031). It
      was not found any association between vitamin D and parameters of heart rate
      variability and heart rate turbulence in IDCM patients. CONCLUSION: Insufficiency
      of vitamin D may have deleterious effects on cardiac autonomic functions which
      were showed with heart rate turbulence and heart rate variability in patients
      with NIDCM. Vitamin D levels might be a predictor to determine the sudden cardiac
      death in patients with non-ischemic etiology.

PMID- 24901022
TI  - No association between scar size and characteristics on T-wave Alternans in post
      myocardial infarction patients with relatively preserved ventricular function
      presented with nonsustained ventricular tachycardia.
AB  - OBJECTIVE: Microvolt T-wave Alternans (TWA) is associated with abnormal
      repolarization and predicts arrhythmic mortality in patients with previous
      myocardial infarction (MI). Infarct tissue size and heterogeneity characterized
      by cardiac magnetic resonance (CMR) has been shown to be associated with
      arrhythmogenic substrates and sudden cardiac death. Although both delayed
      enhancement-CMR (de-CMR) and TWA are useful in risk stratification of post-MI
      patients with preserved left ventricular function, the relationship between scar
      size and TWA has not studied yet. In this study, we aimed to study the relation
      between TWA and scar size and characteristics assessed with CMR in post-MI
      patients (pts) with relatively preserved systolic function presented with
      nonsustained VT. METHODS: This observational cross-sectional study was enrolled
      36 post-MI patients with mild-systolic dysfunction and non-sustained ventricular
      tachycardia. Eight pts were excluded. Both TWA and contrast enhanced CMR were
      performed. Left ventricular ejection fraction (LVEF), dense scar, peri-infarct
      zone and total scar masses were assessed and these values to left ventricular
      (LV) mass ratios were calculated. Infarct ratios and characteristics were
      determined and compared among patients with negative TWA and those with positive
      TWA. RESULTS: For the positive (n=12) vs. negative (n=16) TWA patients there were
      no significant difference between LVEF (44.9 +/- 5.4% vs. 44.0 +/- 3.2%, p=NS)
      and LV masses (121.89 +/- 26.56 g vs. 106.14 +/- 21.16 g, p=NS). The ratio of
      scar core to LV mass (3.37 +/- 0.68% vs. 3.31 +/- 1.01%, p=NS), peri-infarct zone
      to LV mass (23.61 +/- 7.93% vs. 21.64 +/- 9.08%, p=NS), total scar to LV mass
      (26.98 +/- 7.86% vs. 24.96 +/- 9.62%, p=NS) were all similar. CONCLUSION: There
      were no association between scar size and infarct heterogeneity and prevelance of
      TWA in post-MI patients with relatively preserved LVEF with non-sustained VT. Our
      data suggest that these two modalities may reflect different arrhythmogenic
      mechanisms in this cohort.

PMID- 24901023
TI  - Presence of fragmented QRS and its correlation with myocardial performance index
      in patients with nephrotic syndrome.
AB  - OBJECTIVE: More cardiovascular events are seen in nephrotic syndrome (NS)
      patients than in the normal population. Fragmented QRS (fQRS) includes various
      RSR' patterns with different morphologies of the QRS complexes with or without
      the Q wave on a resting 12-lead ECG. A relationship between the presence of fQRS
      and myocardial function impairment has been shown in several studies. The purpose
      of this study was to evaluate the presence of fQRS in this patient group and the
      relationship with myocardial functions. METHODS: Thirty-four NS patients were
      included in the cross-sectional study. Demographic data were recorded, and
      electrocardiograms (ECGs) were analyzed for the presence of fQRS following
      investigation of biochemical parameters and 24-h protein excretion. In addition
      to classic echocardiographic parameters, the myocardial performance (Tei index)
      was calculated as an indicator of cardiac function. For comparison of group's
      data Student's t-test and Mann-Whitney U test were used. Multiple linear
      regression analysis was performed for parameters affecting presence of fQRS.
      RESULTS: We identified fQRS in half of our patients group. Patients with fQRS had
      significantly greater proteinuria level and Tei index than those without (p<0.05
      and p<0.001, respectively). Tei index was also affected presence of fQRS (p<0.05,
      beta=0.45, R2=0.32) and positively correlated with proteinuria levels (p<0.05
      r=0.366). CONCLUSION: We demonstrated, for the first time in the literature, that
      the determination of fQRS in patients with NS in surface ECG, an easily
      accessible technique, can be used as a parameter in the prediction of myocardial
      functions.

PMID- 24901024
TI  - Mean platelet volume and arterial stiffness in patients with acromegaly.
AB  - OBJECTIVE: There are still contradictory data in the literature whether patients
      with acromegaly are under risk in terms of atherosclerotic heart disease.
      Increased arterial stiffness develops before atherosclerosis and is evaluated to
      be a risk factor for atherosclerosis. Mean platelet volume (MPV) is currently
      gaining interest as a new independent cardiovascular risk factor. There are
      contrasting views about arterial stiffness in patients with acromegaly. There is
      no report in literature studying MPV in acromegaly patients. The aim of this
      study was to evaluate MPV and arterial stiffness in patients with acromegaly.
      METHODS: This study was designed as an observational cross-sectional, case
      controlled study. Twenty-eight patients with acromegaly and 22 healthy volunteers
      were recruited for the study. The arteriography device Mobil-O-Graph(r) (IEM
      GmbH. Stolberg, Germany) which can perform oscillometric measurements was used to
      measure arterial stiffness. The Mann-Whitney U test, Student's t-test, Spearman's
      nonparametric correlation analysis and the chi-square test were used to
      statistical analyze. RESULTS: Aortic pulse wave velocity (PWV) value was found to
      be 6.41 +/- 2.12 m/s in the patient group with active acromegaly and 5.24 +/-
      1.04 m/s in the healthy control group. The difference was statistically
      significant (p=0.03). The mean MPV value was found to be 9.68 +/- 1.11 in the
      patient group with active acromegaly and 8.53 +/- 1.18 in the healthy control
      group. There was a statistically significant difference between the two groups
      (p=0.004). In patients with acromegaly, a positive correlation was found between
      MPV and insulin-like growth hormone-I (IGF-1) level (p=0.021, r=0.434).
      CONCLUSION: We determined an increase in aortic PWV and MPV in patients with
      acromegaly. In conclusion, evaluation of MPV and arterial stiffness in future
      studies could be beneficial in determining the risks for cardiovascular disease
      in patients with acromegaly.

PMID- 24901025
TI  - Carotid artery intima-media thickness in pediatric type 1 diabetic patients.
AB  - OBJECTIVE: To compare the carotid artery intima-media thickness in pediatric type
      1 diabetic patients with that in healthy control subjects matched for age, sex,
      height, weight, body mass index (BMI) and waist circumference. METHODS: Fifty
      diabetic patients and forty-five control subjects were enrolled into this
      observational, cross-sectional, controlled study. Carotid artery intima-media
      thickness (cIMT), flow-mediated dilation (FMD) and carotid stiffness index were
      measured by using a carotid Doppler and real-time ultrasound. Student's t, chi
      square and Kolmogorov-Smirnov tests and Pearson's correlation coefficient were
      used for the statistical analysis. RESULTS: There were no significant differences
      in the groups for age, sex, height, weight, BMI and waist circumference (mean age
      12.10 +/- 2.02 vs. 11.49 +/- 1.90 years, weight 41.14 +/- 11.28 vs. 40.88 +/-
      11.68 kg, height 149.78 +/- 20.3 vs. 145.62 +/- 20.14 cm, BMI 18.49 +/- 2.64 vs.
      18.26 +/- 2.59 kg/m2, waist circumference 69.72 +/- 8.6 vs. 66.05 +/- 7.47 cm,
      respectively). A significantly higher cIMT was found in the patients with type 1
      diabetes (0.49 +/- 0.05 vs. 0.44 +/- 0.03 mm; p<0.001). A higher carotid
      stiffness index was found in the diabetic group when compared with control group
      (3.11 +/- 0.46 vs. 2.6 +/- 0.29 mm; p<0.001). Carotid IMT was not affected by
      mean HbA1c level and median HbA1c level (r=0.112, p=0.437 and r=0.249, p=0.082).
      CONCLUSION: Type 1 diabetes is associated with higher cIMT and carotid stiffness
      index in a pediatric population.

PMID- 24901027
TI  - Structural and thermodynamic similarities of phases in the Li-Tt (Tt = Si, Ge)
      systems: redetermination of the lithium-rich side of the Li-Ge phase diagram and
      crystal structures of Li17Si4.0-xGex for x = 2.3, 3.1, 3.5, and 4 as well as
      Li4.1Ge.
AB  - A reinvestigation of the lithium-rich section of the Li-Ge phase diagram reveals
      the existence of two new phases, Li17Ge4 and Li4.10Ge (Li16.38Ge4). Their
      structures are determined by X-ray diffraction experiments of large single
      crystals obtained from equilibrated melts with compositions Li95Ge5 and Li85Ge15.
      Excess melt is subsequently removed through isothermal centrifugation at 400 
      degrees C and 530  degrees C, respectively. Li17Ge4 crystallizes in the space
      group F4[combining macron]3m (a = 18.8521(3) A, V = 6700.1(2) A(3), Z = 20, T =
      298 K) and Li4.10Ge (Li16.38Ge4) in Cmcm (a = 4.5511(2) A, b = 22.0862(7) A, c =
      13.2751(4) A, V = 1334.37(8) A(3), Z = 16, T = 123 K). Both phases are isotypic
      with their Si counterparts and are further representative of the Li17Pb4 and
      Li4.11Si structure types. Additionally, the solid solutions Li17Si4-xGex follows
      Vegard's law. A comparison of the GeLin coordination polyhedra shows that
      isolated Ge atoms are 13- and 14-coordinated in Li17Ge4, whereas in Li16.38Ge4
      the Ge atoms possess coordination numbers 12 and 13. Regarding the thermodynamic
      stability, Li16.38Ge4 is assigned a high-temperature phase existing between ~400 
      degrees C and 627  degrees C, whereas Li17Ge4 decomposes peritectically at 520
      522  degrees C. Additionally, the decomposition of Li16.38Ge4 below ~400  degrees
      C was found to be very sluggish. These findings are manifested by differential
      scanning calorimetry, long-term annealing experiments and the results from melt
      equilibration experiments. Interestingly, the thermodynamic properties of the
      lithium-rich tetrelides Li17Tt4 and Li4.1Tt (Li16.4Tt4) are very similar (Tt =
      Si, Ge). Besides Li15Tt4, Li14Tt6, Li12Tt7, and LiTt, the title compounds are
      further examples of isotypic tetrelides in the systems Li-Tt. 

PMID- 24901026
TI  - Mn K-edge X-ray absorption studies of oxo- and hydroxo-manganese(IV) complexes:
      experimental and theoretical insights into pre-edge properties.
AB  - Mn K-edge X-ray absorption spectroscopy (XAS) was used to gain insights into the
      geometric and electronic structures of [Mn(II)(Cl)2(Me2EBC)],
      [Mn(IV)(OH)2(Me2EBC)](2+), and [Mn(IV)(O)(OH)(Me2EBC)](+), which are all
      supported by the tetradentate, macrocyclic Me2EBC ligand (Me2EBC = 4,11-dimethyl
      1,4,8,11-tetraazabicyclo[6.6.2]hexadecane). Analysis of extended X-ray absorption
      fine structure (EXAFS) data for [Mn(IV)(O)(OH)(Me2EBC)](+) revealed Mn-O
      scatterers at 1.71 and 1.84 A and Mn-N scatterers at 2.11 A, providing the first
      unambiguous support for the formulation of this species as an
      oxohydroxomanganese(IV) adduct. EXAFS-determined structural parameters for
      [Mn(II)(Cl)2(Me2EBC)] and [Mn(IV)(OH)2(Me2EBC)](2+) are consistent with
      previously reported crystal structures. The Mn pre-edge energies and intensities
      of these complexes were examined within the context of data for other oxo- and
      hydroxomanganese(IV) adducts, and time-dependent density functional theory (TD
      DFT) computations were used to predict pre-edge properties for all compounds
      considered. This combined experimental and computational analysis revealed a
      correlation between the Mn-O(H) distances and pre-edge peak areas of Mn(IV)?O and
      Mn(IV)-OH complexes, but this trend was strongly modulated by the Mn(IV)
      coordination geometry. Mn 3d-4p mixing, which primarily accounts for the pre-edge
      intensities, is not solely a function of the Mn-O(H) bond length; the
      coordination geometry also has a large effect on the distribution of pre-edge
      intensity. For tetragonal Mn(IV)?O centers, more than 90% of the pre-edge
      intensity comes from excitations to the Mn?O sigma* MO. Trigonal bipyramidal
      oxomanganese(IV) centers likewise feature excitations to the Mn?O sigma*
      molecular orbital (MO) but also show intense transitions to 3dx(2)-y(2) and 3dxy
      MOs because of enhanced 3d-4px,y mixing. This gives rise to a broader pre-edge
      feature for trigonal Mn(IV)?O adducts. These results underscore the importance of
      reporting experimental pre-edge areas rather than peak heights. Finally, the TD
      DFT method was applied to understand the pre-edge properties of a recently
      reported S = 1 Mn(V)?O adduct; these findings are discussed within the context of
      previous examinations of oxomanganese(V) complexes. 

PMID- 24901028
TI  - Highly fluorescent complexes with 3-isocyanoperylene and N-(2,5-di-tert
      butylphenyl)-9-isocyano-perylene-3,4-dicarboximide.
AB  - The perylene derivatives 3-isocyanoperylene (Per-N=C) (4a) and N-(2,5-di-tert
      butylphenyl)-9-isocyano-perylene-3,4-dicarboximide (PMI-N=C) (4b) were prepared
      and used to synthesize gold complexes [AuX(CNR)] (X = C6F5 (5a,b), C6F4-O(n)Bu-p
      (6b)). The reaction of 5b and 6b with HNEt2 led to the carbene complexes
      [AuX{C(NEt2)(NHR)}] (7b, 8b), respectively. The molecular structure of complexes
      7b and 8b have been determined by X-ray diffraction analysis showing
      intermolecular pi-stacking of the perylene groups and C6F5 rings and no Au...Au
      interactions. The derivative compounds [M(CO)5(CNR)] (M = Cr (9a,b), Mo (10a,b)
      or W (11a,b)) and trans-[Pd(CNR)2(C6F3Cl2)2] (12a,b) were also prepared. All
      complexes exhibit fluorescence associated with the perylene fragment with
      emission quantum yields, in solution at room temperature, in the range 0.05-0.93
      and emission lifetimes ~ 4 ns. DFT calculations were performed of the absorption
      spectra of the ligands Per-N=C and PMI-N=C and representative complexes
      [Au(C6F5)(CNR)], [Cr(CO)5(CNR)], showing a perylene-dominated intraligand pi-pi*
      emissive state, from the HOMO and LUMO orbitals of the perylene chromophore, but
      with significantly different absorption maxima by the influence of the metal
      fragment, particularly significant in the Per-N=C derivatives.

PMID- 24901029
TI  - Crystallographic and spectroscopic insights into heme degradation by
      Mycobacterium tuberculosis MhuD.
AB  - Mycobacterium heme utilization degrader (MhuD) is a heme-degrading protein from
      Mycobacterium tuberculosis responsible for extracting the essential nutrient iron
      from host-derived heme. MhuD has been previously shown to produce unique organic
      products compared to those of canonical heme oxygenases (HOs) as well as those of
      the IsdG/I heme-degrading enzymes from Staphylococcus aureus. Here, we report the
      X-ray crystal structure of cyanide-inhibited MhuD (MhuD-heme-CN) as well as
      detailed (1)H nuclear magnetic resonance (NMR), UV/vis absorption, and magnetic
      circular dichroism (MCD) spectroscopic characterization of this species. There is
      no evidence for an ordered network of water molecules on the distal side of the
      heme substrate in the X-ray crystal structure, as was previously reported for
      canonical HOs. The degree of heme ruffling in the crystal structure of MhuD is
      greater than that observed for HO and less than that observed for IsdI. As a
      consequence, the Fe 3dxz-, 3dyz-, and 3dxy-based MOs are very close in energy,
      and the room-temperature (1)H NMR spectrum of MhuD-heme-CN is consistent with
      population of both a (2)Eg electronic state with a (dxy)(2)(dxz,dyz)(3) electron
      configuration, similar to the ground state of canonical HOs, and a (2)B2g state
      with a (dxz,dyz)(4)(dxy)(1) electron configuration, similar to the ground state
      of cyanide-inhibited IsdI. Variable temperature, variable field MCD saturation
      magnetization data establishes that MhuD-heme-CN has a (2)B2g electronic ground
      state with a low-lying (2)Eg excited state. Our crystallographic and
      spectroscopic data suggest that there are both structural and electronic
      contributions to the alpha-meso regioselectivity of MhuD-catalyzed heme cleavage.
      The structural distortion of the heme substrate observed in the X-ray crystal
      structure of MhuD-heme-CN is likely to favor cleavage at the alpha- and gamma
      meso carbons, whereas the spin density distribution may favor selective
      oxygenation of the alpha-meso carbon. 

PMID- 24901030
TI  - Improved peripheral nerve regeneration using acellular nerve allografts loaded
      with platelet-rich plasma.
AB  - Acellular nerve allografts (ANAs) behave in a similar manner to autografts in
      supporting axonal regeneration in the repair of short peripheral nerve defects
      but fail in larger defects. The objective of this article is to evaluate the
      effect of ANA supplemented with platelet-rich plasma (PRP) to improve nerve
      regeneration after surgical repair and to discuss the mechanisms that underlie
      this approach. Autologous PRP was obtained from rats by double-step
      centrifugation and was characterized by determining platelet numbers and the
      release of growth factors. Forty-eight Sprague-Dawley rats were randomly divided
      into 4 groups (12/group), identified as autograft, ANA, ANA loaded with PRP
      (ANA+PRP), and ANA loaded with platelet-poor plasma (PPP, ANA+PPP). All grafts
      were implanted to bridge long-gap (15 mm) sciatic nerve defects. We found that
      PRP with a high platelet concentration exhibited a sustained release of growth
      factors. Twelve weeks after surgery, the autograft group displayed the highest
      level of reinnervation, followed by the ANA+PRP group. The ANA+PRP group showed a
      better electrophysiology response for amplitude and conduction velocity than the
      ANA and ANA+PPP groups. Based on histological evaluation, the ANA+PRP and
      autograft groups had higher numbers of regenerating nerve fibers. Quantitative
      real-time polymerase chain reaction (qRT-PCR) demonstrated that PRP boosted
      expression of neurotrophins in the regenerated nerves. Moreover, the ANA+PRP and
      autograft groups showed excellent physiological outcomes in terms of the
      prevention of muscle atrophy. In conclusion, ANAs loaded with PRP as tissue
      engineered scaffolds can enhance nerve regeneration and functional recovery after
      the repair of large nerve gaps nearly as well as autografts. 

PMID- 24901031
TI  - Impact of fillers on dissolution kinetic of fenofibrate dry foams.
AB  - Dry foam technology reveals the opportunity to improve the dissolution behavior
      of poorly soluble drugs tending to agglomeration due to micronization. In this
      study, the impact of fillers on the manufacturability, the properties of dry
      foams and granules as well as the dissolution kinetics of dry foam tablets was
      investigated using fenofibrate as a model compound. Different maltodextrins and
      dried glucose syrups, a maltodextrin-phosphatidylcholine complex, isomalt and a
      1:1 mixture of mannitol/glucose syrup were used as filler. Within the group of
      maltodextrins and glucose syrups, the influences of dextrose equivalent (DE),
      particle morphology and botanical source of starch were investigated. Comparable
      macroscopic foam structures were obtained with maltodextrins and glucose syrups
      whereas different foam morphologies were obtained for the other fillers tested.
      Regarding the maltodextrins and glucose syrups, different physicochemical and
      particle properties had a minor impact on granule characteristics and tablet
      dissolution. Using the maltodextrin-phosphatidylcholine complex resulted in a low
      specific surface area of the granules and a slow tablet dissolution caused by a
      slow disintegration. In contrast, a high specific surface area and a fast release
      were obtained with isomalt and glucose syrup/mannitol mixture indicating that
      high soluble low molecular weight fillers enable the development of fast
      dissolving dry foam tablets. 

PMID- 24901032
TI  - Enzyme-assisted target recycling (EATR) for nucleic acid detection.
AB  - Fast, reliable and sensitive methods for nucleic acid detection are of growing
      practical interest with respect to molecular diagnostics of cancer, infectious
      and genetic diseases. Currently, PCR-based and other target amplification
      strategies are most extensively used in practice. At the same time, such assays
      have limitations that can be overcome by alternative approaches. There is a
      recent explosion in the design of methods that amplify the signal produced by a
      nucleic acid target, without changing its copy number. This review aims at
      systematization and critical analysis of the enzyme-assisted target recycling
      (EATR) signal amplification technique. The approach uses nucleases to recognize
      and cleave the probe-target complex. Cleavage reactions produce a detectable
      signal. The advantages of such techniques are potentially low sensitivity to
      contamination and lack of the requirement of a thermal cycler. Nucleases used for
      EATR include sequence-dependent restriction or nicking endonucleases or sequence
      independent exonuclease III, lambda exonuclease, RNase H, RNase HII, AP
      endonuclease, duplex-specific nuclease, DNase I, or T7 exonuclease. EATR-based
      assays are potentially useful for point-of-care diagnostics, single nucleotide
      polymorphisms genotyping and microRNA analysis. Specificity, limit of detection
      and the potential impact of EATR strategies on molecular diagnostics are
      discussed. 

PMID- 24901033
TI  - An insight into structure and stability of DNA in ionic liquids from molecular
      dynamics simulation and experimental studies.
AB  - Molecular dynamics simulation and biophysical analysis were employed to reveal
      the characteristics and the influence of ionic liquids (ILs) on the structural
      properties of DNA. Both computational and experimental evidence indicate that DNA
      retains its native B-conformation in ILs. Simulation data show that the hydration
      shells around the DNA phosphate group were the main criteria for DNA
      stabilization in this ionic media. Stronger hydration shells reduce the binding
      ability of ILs' cations to the DNA phosphate group, thus destabilizing the DNA.
      The simulation results also indicated that the DNA structure maintains its duplex
      conformation when solvated by ILs at different temperatures up to 373.15 K. The
      result further suggests that the thermal stability of DNA at high temperatures is
      related to the solvent thermodynamics, especially entropy and enthalpy of water.
      All the molecular simulation results were consistent with the experimental
      findings. The understanding of the properties of IL-DNA could be used as a basis
      for future development of specific ILs for nucleic acid technology. 

PMID- 24901034
TI  - A discrete neutral transition-metal citrate cubane with an M4O4 core;
      coordinative versatility of the [M(II)4(citrate)4]8- fragment.
AB  - The neutral cluster [Mn(II)8(citrate)4(H2O)18] is formed by the [M4(citrate)4](8
      ) fragment, with an Mn4O4 cubane core, which bonds four peripheral aquomanganese
      units--two [Mn(H2O)4](2+) and two [Mn(H2O)5](2+)--through a total of six metal
      ligand bonds, giving a discrete neutral compound. The compound presents a unique
      coordination mode in which the citrate cubane acts as a chelate to each of the
      two peripheral [Mn(H2O)4](2+) (tetra-aquo) units. A detailed analysis of the
      central and peripheral geometries is given in terms of the tetrahedral
      distortions of key structural features. A reversible dehydration-rehydration
      process has been observed in a polycrystalline sample of the complex, whose
      structure lacks pores or channels.

PMID- 24901035
TI  - Investigating the effects of block versus statistical glycopolycations containing
      primary and tertiary amines for plasmid DNA delivery.
AB  - Polymer composition and morphology can affect the way polymers interact with
      biomolecules, cell membranes, and intracellular components. Herein, diblock,
      triblock, and statistical polymers that varied in charge center type (primary
      and/or tertiary amines) were synthesized to elucidate the role of polymer
      composition on plasmid DNA complexation, delivery, and cellular toxicity of the
      resultant polyplexes. The polymers were synthesized via RAFT polymerization and
      were composed of a carbohydrate moiety, 2-deoxy-2-methacrylamido glucopyranose
      (MAG), a primary amine group, N-(2-aminoethyl) methacrylamide (AEMA), and/or a
      tertiary amine moiety, N,N-(2-dimethylamino)ethyl methacrylamide (DMAEMA). The
      lengths of both the carbohydrate and cationic blocks were kept constant while the
      primary amine to tertiary amine ratio was varied within the polymers. The
      polymers were characterized via nuclear magnetic resonance (NMR) and size
      exclusion chromatography (SEC), and the polyplex formulations with pDNA were
      characterized in various media using dynamic light scattering (DLS). Polyplexes
      formed with the block copolymers were found to be more colloidally stable than
      statistical copolymers with similar composition, which rapidly aggregated to
      micrometer sized particles. Also, polymers composed of a higher primary amine
      content were more colloidally stable than polymers consisting of the tertiary
      amine charge centers. Plasmid DNA internalization, transgene expression, and
      toxicity were examined with each polymer. As the amount of tertiary amine in the
      triblock copolymers increased, both gene expression and toxicity were found to
      increase. Moreover, it was found that increasing the content of tertiary amines
      imparted higher membrane disruption/destabilization. While both block and
      statistical copolymers had high transfection efficiencies, some of the
      statistical systems exhibited both higher transfection and toxicity than the
      analogous block polymers, potentially due to the lack of a hydrophilic block to
      screen membrane interaction/disruption. Overall, the triblock terpolymers offer
      an attractive composition profile that exhibited interesting properties as pDNA
      delivery vehicles. 

PMID- 24901037
TI  - Performance of the MM/GBSA scoring using a binding site hydrogen bond network
      based frame selection: the protein kinase case.
AB  - A conformational selection method, based on hydrogen bond (Hbond) network
      analysis, has been designed in order to rationalize the configurations sampled
      using molecular dynamics (MD), which are commonly used in the estimation of the
      relative binding free energy of ligands to macromolecules through the MM/GBSA or
      MM/PBSA method. This approach makes use of protein-ligand complexes obtained from
      X-ray crystallographic data, as well as from molecular docking calculations. The
      combination of several computational approaches, like long MD simulations on
      protein-ligand complexes, Hbond network-based selection by scripting techniques
      and finally MM/GBSA, provides better statistical correlations against
      experimental binding data than previous similar reported studies. This approach
      has been successfully applied in the ranking of several protein kinase inhibitors
      (CDK2, Aurora A and p38), which present both diverse and related chemical
      structures. 

PMID- 24901036
TI  - Evolution of functional connectivity of brain networks and their dynamic
      interaction in temporal lobe epilepsy.
AB  - This study presents a cross-sectional investigation of functional networks in
      temporal lobe epilepsy (TLE) as they evolve over years of disease. Networks of
      interest were identified based on a priori hypotheses: the network of seizure
      propagation ipsilateral to the seizure focus, the same regions contralateral to
      seizure focus, the cross hemisphere network of the same regions, and a cingulate
      midline network. Resting functional magnetic resonance imaging data were acquired
      for 20 min in 12 unilateral TLE patients, and 12 age- and gender-matched healthy
      controls. Functional changes within and between the four networks as they evolve
      over years of disease were quantified by standard measures of static functional
      connectivity and novel measures of dynamic functional connectivity. The results
      suggest an initial disruption of cross-hemispheric networks and an increase in
      static functional connectivity in the ipsilateral temporal network accompanying
      the onset of TLE seizures. As seizures progress over years, the static functional
      connectivity across the ipsilateral network diminishes, while dynamic functional
      connectivity measures show the functional independence of this ipsilateral
      network from the network of midline regions of the cingulate declines. This
      implies a gradual breakdown of the seizure onset and early propagation network
      involving the ipsilateral hippocampus and temporal lobe as it becomes more
      synchronous with the network of regions responsible for secondary generalization
      of the seizures, a process that may facilitate the spread of seizures across the
      brain. Ultimately, the significance of this evolution may be realized in relating
      it to symptoms and treatment outcomes of TLE.

PMID- 24901039
TI  - Annealing effects on the properties of BFe2As2 (B = Ca, Sr, Ba) superconducting
      parents.
AB  - The effects of thermal-annealing on the antiferromagnetic (TN) and structural
      (Ts) transition temperatures of ThCr2Si2-type BaFe2As2 and SrFe2As2 ('122')
      crystals are reported and compared to that of CaFe2As2. Although the shift in
      transition temperature for CaFe2As2 can be as high as 75 K, we find modest
      changes of ~6 K for BaFe2As2 and SrFe2As2. Such findings are based on the
      measurements of temperature dependence of electrical resistivity, magnetization,
      and heat capacity. Residual resistivity ratios show an improvement of crystal
      quality upon annealing for both BaFe2As2 and SrFe2As2. We confirm the pressure
      like influence of annealing on the 122 crystals. 

PMID- 24901038
TI  - Imparting superhydrophobicity to biodegradable poly(lactide-co-glycolide)
      electrospun meshes.
AB  - The synthesis of a family of new poly(lactic acid-co-glycerol monostearate) (PLA
      PGC18) copolymers and their use as biodegradable polymer dopants is reported to
      enhance the hydrophobicity of poly(lactic acid-co-glycolic acid) (PLGA) nonwoven
      meshes. Solutions of PLGA are doped with PLA-PGC18 and electrospun to form meshes
      with micrometer-sized fibers. Fiber diameter, percent doping, and copolymer
      composition influence the nonwetting nature of the meshes and alter their
      mechanical (tensile) properties. Contact angles as high as 160 degrees  are
      obtained with 30% polymer dopant. Lastly, these meshes are nontoxic, as
      determined by an NIH/3T3 cell biocompatibility assay, and displayed a minimal
      foreign body response when implanted in mice. In summary, a general method for
      constructing biodegradable fibrous meshes with tunable hydrophobicity is
      described for use in tissue engineering and drug delivery applications. 

PMID- 24901040
TI  - Effect of deafferentation from spinal anesthesia on pain sensitivity and resting
      state functional brain connectivity in healthy male volunteers.
AB  - Patients may perceive paradoxical heat sensation during spinal anesthesia. This
      could be due to deafferentation-related functional changes at cortical,
      subcortical, or spinal levels. In the current study, the effect of spinal
      deafferentation on sensory (pain) sensitivity was studied and linked to whole
      brain functional connectivity as assessed by resting-state functional magnetic
      resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or
      spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS
      fMRI brain connectivity was determined in relation to eight predefined and seven
      thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after
      spinal/sham injection. To measure the effect of deafferentation on pain
      sensitivity, responses to heat pain were measured at 15-min intervals on
      nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal
      anesthesia altered functional brain connectivity within brain regions involved in
      the sensory discriminative (i.e., pain intensity related) and affective
      dimensions of pain perception in relation to somatosensory and thalamic RSNs. A
      significant enhancement of pain sensitivity on nondeafferented skin was observed
      after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]:
      190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to
      functional connectivity changes observed within the thalamus in relation to the
      thalamo-prefrontal network, and in the anterior cingulate cortex and insula in
      relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal
      deafferentation correlated with functional connectivity changes within brain
      regions involved in affective and sensory pain processing and areas involved in
      descending control of pain.

PMID- 24901041
TI  - Evaluation of the efficiency of enological procedures on lysozyme depletion in
      wine by an indirect ELISA method.
AB  - Potential residues of the potent allergen lysozyme used as a microbial
      stabilizing agent in wine production might pose a serious health thread to
      susceptible individuals. Therefore, EU legislation requires the labeling of the
      allergenic agent, if it is present in the final product. To allow for product
      testing, an indirect ELISA method to be specifically used in wine analysis was
      developed and validated. Furthermore, trial wines treated with defined amounts of
      lysozyme were subjected to an array of different filtration and other enological
      processing regimes in order to evaluate their potential to deplete the allergen
      content of the wines. By these means, processing methods ought to be identified
      that can be integrated in a good manufacturing practice guideline to enable wine
      producers to utilize lysozyme in their cellars and still provide wines free of
      allergenic residues. However, among the enological procedures under scrutiny,
      only bentonite fining proved to be capable of significantly reducing the
      allergenic residues. 

PMID- 24901042
TI  - Modulation of nitric oxide by flavonoids.
AB  - One of the main mechanisms by which dietary flavonoids are thought to influence
      cardiovascular disease is via protection of the bioactivity of the endothelium
      derived nitric oxide (NO). Additionally, flavonoids may also interfere with the
      signalling cascades of inflammation and prevent overproduction of NO and its
      deleterious consequences in shock and ischemia-reperfusion injury. In the present
      paper we review the evidence of the effects of flavonoids on NO. Flavonoids exert
      complex actions on the synthesis and bioavailability of NO which may result both
      in enhanced or decreased NO levels: (1) in cell free systems, several flavonoids
      may scavenge NO via its pro-oxidant properties by increasing superoxide. However,
      under conditions of oxidative stress, flavonoids may also protect NO from
      superoxide-driven inactivation. (2) In intact healthy tissues, some flavonoids
      increase eNOS activity in endothelial cells. Paradoxically this effect involves a
      pro-oxidant effect which results in Ca(2+)-dependent activation of eNOS. As
      inhibitors of PI3K, flavonoids may potentially inhibit the PI3K/Akt-dependent
      activation of eNOS. (3) Under conditions of inflammation and oxidative stress,
      flavonoids may prevent the inflammatory signalling cascades via inhibition of
      NFkappaB and thereby downregulate iNOS. On the other hand, they also prevent the
      overexpression of ROS generating enzymes, reducing superoxide and peroxynitrite
      levels, and hence preventing superoxide-induced NO inactivation and eNOS
      uncoupling. Therefore, the final effect of flavonoids on NO levels will depend on
      the flavonoid structure and the concentrations used, on the cell type under study
      and particularly on the presence of inflammatory/oxidative conditions. 

PMID- 24901043
TI  - Growth dynamics in supersonic molecular beam deposition of pentacene sub
      monolayers on SiO2.
AB  - Studying highly energetic pentacene impinging on a surface, we demonstrated that
      the perpendicular component of the momentum drives the dynamics of molecule
      molecule interactions and hence the island nucleation process, while the parallel
      component governs the dynamics of the interactions between the surface and the
      molecule and therefore determines the sticking coefficient and the island
      fractality. 

PMID- 24901044
TI  - FADD regulates thymocyte development at the beta-selection checkpoint by
      modulating Notch signaling.
AB  - Non-apoptotic functions of Fas-associated protein with death domain (FADD) have
      been implicated in T lineage lymphocytes, but the nature of FADD-dependent non
      apoptotic mechanism in early T-cell development has not been completely
      elucidated. In this study, we show that tissue-specific deletion of FADD in
      immature (CD44(-)CD25(+)) thymocytes results in severe perturbation of alphabeta
      lineage development. Meanwhile, loss of FADD signaling at a later (CD44(-)CD25(
      )) developmental stage does not affect subsequent T-cell development.
      Collectively, our work presents that FADD deficiency induces failed survival in
      double-negative 4 (DN4) cells, while pre-T-cell receptor (TCR) signal remains
      intact. In addition, Notch signaling is positive regulated on DN4 and double
      positive thymocytes in T-cell-specific FADD-knockout mice, which express higher
      levels of a subset of Notch-target genes, including Hes1, Deltex1 and CD25.
      Moreover, a transcriptional repressor of Notch1, NKAP is downregulated coupled
      with the loss of FADD in thymocytes and is found to associate with FADD. These
      data suggest that as a death receptor, FADD is also required for cell survival in
      beta-selection as a regulator of Notch1 expression. 

PMID- 24901045
TI  - Retinoblastoma protein (RB) interacts with E2F3 to control terminal
      differentiation of Sertoli cells.
AB  - The retinoblastoma protein (RB) is essential for normal cell cycle control. RB
      function depends, at least in part, on interactions with the E2F family of DNA
      binding transcription factors (E2Fs). To study the role of RB in the adult
      testis, a Sertoli cell (SC)-specific Rb knockout mouse line (SC-RbKO) was
      generated using the Cre/loxP recombination system. SC-RbKO mice exhibited an age
      dependent testicular atrophy, impaired fertility, severe SC dysfunction, and
      spermatogenic defects. Removal of Rb in SC induced aberrant SC cycling,
      dedifferentiation, and apoptosis. Here we show that E2F3 is the only E2F
      expressed in mouse SCs and that RB interacts with E2F3 during mouse testicular
      development. In the absence of RB, the other retinoblastoma family members p107
      and p130 began interacting with E2F3 in the adult testes. In vivo silencing of
      E2F3 partially restored the SC maturation and survival as well as spermatogenesis
      in the SC-RbKO mice. These results point to RB as a key regulator of SC function
      in adult mice and that the RB/E2F3 pathway directs SC maturation, cell cycle
      quiescence, and RB protects SC from apoptosis. 

PMID- 24901046
TI  - Apolipoprotein L2 contains a BH3-like domain but it does not behave as a BH3-only
      protein.
AB  - Apolipoproteins of the L family are lipid-binding proteins whose function is
      largely unknown. Apolipoprotein L1 and apolipoprotein L6 have been recently
      described as novel pro-death BH3-only proteins that are also capable of
      regulating autophagy. In an in-silico screening to discover novel putative BH3
      only proteins, we identified yet another member of the apolipoprotein L family,
      apolipoprotein L2 (ApoL2), as a BH3 motif-containing protein. ApoL2 has been
      suggested to behave as a BH3-only protein and mediate cell death induced by
      interferon-gamma or viral infection. As previously described, we observed that
      ApoL2 protein was induced by interferon-gamma. However, knocking down its
      expression in HeLa cells did not regulate cell death induced by interferon-gamma.
      Overexpression of ApoL2 did not induce cell death on its own. ApoL2 did not
      sensitize or protect cells from overexpression of the BH3-only proteins Bmf or
      Noxa. Furthermore, siRNA against ApoL2 did not alter sensitivity to a variety of
      death stimuli. We could, however, detect a weak interaction between ApoL2 and Bcl
      2 by immunoprecipitation of the former, suggesting a role of ApoL2 in a Bcl-2
      regulated process like autophagy. However, in contrast to what has been described
      about its homologs ApoL1 and ApoL6, ApoL2 did not regulate autophagy. Thus, the
      role, if any, of ApoL2 in cell death remains to be clarified. 

PMID- 24901048
TI  - Multiple partners can kiss-and-run: Bax transfers between multiple membranes and
      permeabilizes those primed by tBid.
AB  - During apoptosis Bid and Bax are sufficient for mitochondrial outer membrane
      permeabilization, releasing pro-apoptotic proteins such as cytochrome c and
      Smac/Diablo into the cytoplasm. In most cells, both Bid and Bax are cytoplasmic
      but bind to mitochondrial outer membranes to exert pro-apoptotic functions.
      Binding to membranes is regulated by cleavage of Bid to truncated Bid (tBid), by
      conformation changes in tBid and Bax, and by interactions with other proteins. At
      least at the peripherally bound stage, binding is reversible. Therefore,
      regulation of apoptosis is closely linked with the interactions of tBid and Bax
      with mitochondria. Here we use fluorescence techniques and cell-free systems
      containing mitochondria or liposomes that faithfully mimic tBid/Bax-dependent
      membrane permeabilization to study the dynamic interactions of the proteins with
      membranes. We confirm that the binding of both proteins to the membrane is
      reversible by quantifying the binding affinity of proteins for the membrane. For
      Bax, both peripherally bound (inactive) and oligomerized (active) proteins
      migrate between membranes but much slower than and independent of tBid. When re
      localized to a new membrane, Bax inserts into and permeabilizes it only if primed
      by an activator. In the case of tBid, the process of transfer is synergetic with
      Bax in the sense that tBid 'runs' faster if it has been 'kissed' by Bax.
      Furthermore, Mtch2 accelerates the re-localization of tBid at the mitochondria.
      In contrast, binding to Bcl-XL dramatically impedes tBid re-localization by
      lowering the off-rate threefold. Our results suggest that the transfer of
      activated tBid and Bax to different mitochondria is governed by dynamic
      equilibria and potentially contributes more than previously anticipated to the
      dissemination of the permeabilization signal within the cell. 

PMID- 24901049
TI  - The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates
      acetaminophen-induced liver injury.
AB  - Receptor-interacting protein (RIP)3 is a critical regulator of necroptosis and
      has been demonstrated to be associated with various diseases, suggesting that its
      inhibitors are promising in the clinic. However, there have been few RIP3
      inhibitors reported as yet. B-Raf(V600E) inhibitors are an important anticancer
      drug class for metastatic melanoma therapy. In this study, we found that 6 B-Raf
      inhibitors could inhibit RIP3 enzymatic activity in vitro. Among them, dabrafenib
      showed the most potent inhibition on RIP3, which was achieved by its ATP
      competitive binding to the enzyme. Dabrafenib displayed highly selective
      inhibition on RIP3 over RIP1, RIP2 and RIP5. Moreover, only dabrafenib rescued
      cells from RIP3-mediated necroptosis induced by the necroptosis-induced
      combinations, that is, tumor necrosis factor (TNF)alpha, TNF-related apoptosis
      inducing ligand or Fas ligand plus Smac mimetic and the caspase inhibitor z-VAD.
      Dabrafenib decreased the RIP3-mediated Ser358 phosphorylation of mixed lineage
      kinase domain-like protein (MLKL) and disrupted the interaction between RIP3 and
      MLKL. Notably, RIP3 inhibition of dabrafenib appeared to be independent of its B
      Raf inhibition. Dabrafenib was further revealed to prevent acetaminophen-induced
      necrosis in normal human hepatocytes, which is considered to be mediated by RIP3.
      In acetaminophen-overdosed mouse models, dabrafenib was found to apparently ease
      the acetaminophen-caused liver damage. The results indicate that the anticancer B
      Raf(V600E) inhibitor dabrafenib is a RIP3 inhibitor, which could serve as a sharp
      tool for probing the RIP3 biology and as a potential preventive or therapeutic
      agent for RIP3-involved necroptosis-related diseases such as acetaminophen
      induced liver damage. 

PMID- 24901050
TI  - miR-125b controls apoptosis and temozolomide resistance by targeting TNFAIP3 and
      NKIRAS2 in glioblastomas.
AB  - Diffusely infiltrating gliomas are among the most prognostically discouraging
      neoplasia in human. Temozolomide (TMZ) in combination with radiotherapy is
      currently used for the treatment of glioblastoma (GBM) patients, but less than
      half of the patients respond to therapy and chemoresistance develops rapidly.
      Epigenetic silencing of the O(6)-methylguanine-DNA methyltransferase (MGMT) has
      been associated with longer survival in GBM patients treated with TMZ, but
      nuclear factor kappaB (NF-kappaB)-mediated survival signaling and TP53 mutations
      contribute significantly to TMZ resistance. Enhanced NF-kappaB is in part owing
      to downregulation of negative regulators of NF-kappaB activity, including Tumor
      necrosis factor alpha-induced protein 3 (TNFAIP3) and NF-kappaB inhibitor
      interacting RAS-like 2 (NKIRAS2). Here we provide a novel mechanism independent
      of TP53 and MGMT by which oncogenic miR-125b confers TMZ resistance by targeting
      TNFAIP3 and NKIRAS2. GBM cells overexpressing miR-125b showed increased NF-kappaB
      activity and upregulation of anti-apoptotic and cell cycle genes. This was
      significantly associated with resistance of GBM cells to TNFalpha- and TNF
      related inducing ligand-induced apoptosis as well as resistance to TMZ.
      Conversely, overexpression of anti-miR-125b resulted in cell cycle arrest,
      increased apoptosis and increased sensitivity to TMZ, indicating that endogenous
      miR-125b is sufficient to control these processes. GBM cells overexpressing
      TNFAIP3 and NKIRAS2 were refractory to miR-125b-induced apoptosis resistance as
      well as TMZ resistance, indicating that both genes are relevant targets of miR
      125b. In GBM tissues, high miR-125b expression was significantly correlated with
      nuclear NF-kappaB confirming that miR-125b is implicated in NF-kappaB signaling.
      Most remarkably, miR-125b overexpression was clearly associated with shorter
      overall survival of patients treated with TMZ, suggesting that this microRNA is
      an important predictor of response to therapy. 

PMID- 24901051
TI  - DeltaNp63alpha activates CD82 metastasis suppressor to inhibit cancer cell
      invasion.
AB  - P63 is a p53 family member involved in multiple facets of biology, including
      embryonic development, cell proliferation, differentiation, survival, apoptosis,
      senescence and aging. The p63 gene encodes multiple protein isoforms either with
      (TAp63) or without (DeltaNp63) the N-terminal transactivation domain. Amounting
      evidence suggests that p63 can function as a tumor suppressor, yet the precise
      molecular mechanisms, and particularly the specific roles of TAp63 and DeltaNp63
      in cancer progression, are still largely unclear. Here, we demonstrated that
      DeltaNp63alpha, the predominant isoform expressed in epithelial cells and
      squamous cell carcinomas, inhibits cell invasion. Affymetrix gene expression
      profiling, combined with gain- and loss-of-function analyses and chromatin
      immunoprecipitation, indicated that cluster of differentiation 82 (CD82), a
      documented metastasis suppressor, is a direct transcriptional target of
      DeltaNp63alpha. Expression of DeltaNp63alpha inhibited outgrowth in Matrigel and
      cancer cell invasion, which was largely reversed by specific ablation of CD82.
      Conversely, DeltaNp63alpha knockdown led to increased cell invasion, which was
      reversed by ectopic expression of CD82. Moreover, inhibition of glycogen synthase
      kinase-3beta (GSK3beta) by either pharmacological inhibitors or by RNA
      interference resulted in the downregulation of DeltaNp63alpha and CD82
      expression, concomitant with increased cell invasion, independently of beta
      catenin. Furthermore, decreased expression of p63 and CD82 is correlated with
      cancer progression. Taken together, this study reveals that DeltaNp63alpha
      upregulates CD82 to inhibit cell invasion, and suggests that GSK3beta can
      regulate cell invasion by modulating the DeltaNp63alpha-CD82 axis. 

PMID- 24901052
TI  - Rapamycin-enhanced mitomycin C-induced apoptotic death is mediated through the
      S6K1-Bad-Bak pathway in peritoneal carcinomatosis.
AB  - Peritoneal carcinomatosis (PC) is the most common secondary cancerous disease,
      and more effective novel regimens are needed. In this study, we identified a
      novel combination treatment for PC, chemotherapeutic agent mitomycin C in
      combination with mTOR (mammalian target of rapamycin) inhibitor rapamycin. We
      observed that the combination of mitomycin C and rapamycin induced synergistic
      cytotoxicity and apoptosis, which was mediated through an increase in caspase
      activation. The combination of mitomycin C and rapamycin inactivated p70 S6
      ribosomal kinase (S6K1) and dephosphorylated Bad, leading to dissociation of Bcl
      xL from Bak, which resulted in Bak oligomerization, mitochondria dysfunction and
      cytochrome c release. PF-4708671, a S6K1-specific inhibitor, enhanced the
      combination treatment-induced apoptosis, whereas S6K1 E389 DeltaCT-HA (S6K1
      active form) dramatically decreased the induction of apoptosis. In addition, the
      combination treatment significantly inhibited LS174T intraperitoneal tumor growth
      in vivo. This study provides a preclinical rationale for apoptosis induction
      linked with the mTOR pathway through a combination of chemotherapeutic agents and
      mTOR inhibitor, and will support this combinatorial strategy to PC patients. 

PMID- 24901053
TI  - alphaNAC inhibition of the FADD-JNK axis plays anti-apoptotic role in multiple
      cancer cells.
AB  - Nascent polypeptide-associated complex alpha (alphaNAC) is reportedly
      overexpressed in several types of cancers and regulates cell apoptosis under
      hypoxic conditions in HeLa cells. The aim of our study was to investigate the
      apoptotic function of alphaNAC in cancer progression. First, we observed the
      cellular effects of alphaNAC depletion. Mouse alphaNAC was used to restore the
      protein level and verify the effect. An Annexin V assay, a caspase activity
      reporter assay, an apoptotic molecular marker, and a colony formation assay were
      used as markers to investigate the mechanisms of cell death caused by alphaNAC
      depletion. The Cancer 10-pathway reporter assay was used to screen downstream
      pathways. PCR site-directed deletion based on the functional domains of alphaNAC
      was used to construct deletion mutants. Those functional domain deletion mutants
      were used to recover the apoptotic phenotype caused by alphaNAC depletion.
      Finally, the role of alphaNAC in TNF-related apoptosis-inducing ligand (TRAIL)
      treatment was investigated in vitro. We found that depletion of alphaNAC in
      multiple types of cancer cells induce typical apoptotic cell death. This anti
      apoptotic function is mediated by the FADD/c-Jun N-terminal kinase pathway.
      Intact alphaNAC is required for the direct binding of FADD as well as its anti
      apoptosis function. Either alphaNAC depletion or the deletion of the ubiquitin
      associated domain of alphaNAC sensitizes L929 cancer cells to mTRAIL treatment.
      Our study revealed a alphaNAC anti-apoptotic function in multiple types of cancer
      cells and suggested its potential in cancer therapy. 

PMID- 24901054
TI  - NF-kappaB and Nrf2 signaling pathways contribute to wogonin-mediated inhibition
      of inflammation-associated colorectal carcinogenesis.
AB  - The transcriptional factors nuclear factor-kappaB (NF-kappaB) and NF-E2-related
      factor 2 (Nrf2) have been recently reported to have critical roles in protecting
      various tissues against inflammation and colitis-associated colorectal cancer
      (aberrant crypt foci). Our previous studies showed that wogonin (5,7-dihydroxy-8
      methoxyflavone) possessed anti-neoplastic and anti-inflammatory activities. The
      present study extended these important earlier findings by exploring the effect
      of wogonin on the initiation and development of colitis-associated cancer.
      Wogonin lowered tumor incidence and inhibited the development of colorectal
      adenomas in azoxymethane- or dextran sulfate sodium-induced mice. We found that
      wogonin significantly decreased the secretion and expression of IL-6 and IL
      1beta, reduced cell proliferation and nuclear expression of NF-kappaB in adenomas
      and surrounding tissues and promoted Nrf2 nuclear translocation in surrounding
      tissues, although overexpressed Nrf2 in tumor tissues was independent of wogonin
      administration. Furthermore, wogonin inhibited the interaction between human
      monocytic THP-1 cells and human colon cancer HCT116 cells, and significantly
      downregulated lipopolysaccharide-induced secretion of prototypical pro
      inflammatory cytokines IL-6 and IL-1beta in THP-1 cells. Further mechanism
      research revealed that wogonin inhibited the nuclear translocation of NF-kappaB
      and phosphorylation of IkappaB and IKKalpha/beta, and promoted Nrf2 signaling
      pathway in HCT116 cells and THP-1 cells. Taken together, the present results
      indicated that wogonin effectively suppressed inflammation-associated colon
      carcinogenesis and cancer development, suggesting its potential as a
      chemopreventive agent against colitis-associated colon cancer. 

PMID- 24901055
TI  - Rnd3 haploinsufficient mice are predisposed to hemodynamic stress and develop
      apoptotic cardiomyopathy with heart failure.
AB  - Rho family guanosine triphosphatase (GTPase) 3 (Rnd3), a member of the small Rho
      GTPase family, has been suggested to regulate cell actin cytoskeleton dynamics,
      cell migration, and apoptosis through the Rho kinase-dependent signaling pathway.
      The biological function of Rnd3 in the heart is unknown. The downregulation of
      small GTPase Rnd3 transcripts was found in patients with end-stage heart failure.
      The pathological significance of Rnd3 loss in the transition to heart failure
      remains unexplored. To investigate the functional consequence of Rnd3
      downregulation and the associated molecular mechanism, we generated Rnd3(+/-)
      haploinsufficient mice to mimic the downregulation of Rnd3 observed in the
      failing human heart. Rnd3(+/-) mice were viable; however, the mice developed
      heart failure after pressure overload by transverse aortic constriction (TAC).
      Remarkable apoptosis, increased caspase-3 activity, and elevated Rho kinase
      activity were detected in the Rnd3(+/-) haploinsufficient animal hearts.
      Pharmacological inhibition of Rho kinase by fasudil treatment partially improved
      Rnd3(+/-) mouse cardiac functions and attenuated myocardial apoptosis. To
      determine if Rho-associated coiled-coil kinase 1 (ROCK1) was responsible for Rnd3
      deficiency-mediated apoptotic cardiomyopathy, we established a double-knockout
      mouse line, the Rnd3 haploinsufficient mice with ROCK1-null background (Rnd3(+/
      /ROCK1-/-)). Again, genetic deletion of ROCK1 partially but not completely
      rescued Rnd3 deficiency-mediated heart failure phenotype. These data suggest that
      downregulation of Rnd3 correlates with cardiac loss of function as in heart
      failure patients. Animals with Rnd3 haploinsufficiency are predisposed to
      hemodynamic stress. Hyperactivation of Rho kinase activity is responsible in part
      for the apoptotic cardiomyopathy development. Further investigation of ROCK1
      independent mechanisms in Rnd3-mediated cardiac remodeling should be the focus
      for future study. 

PMID- 24901058
TI  - Suicide prevention e-learning modules designed for gatekeepers: a descriptive
      review.
AB  - BACKGROUND: E-learning modules can be a useful method for educating gatekeepers
      in suicide prevention and awareness. AIMS: To review and provide an overview of e
      learning modules on suicide prevention designed for gatekeepers and assess their
      effectiveness. METHOD: Two strategies were used. First, articles were
      systematically searched in databases of PubMed, Web of Science, and PsycINFO.
      Second, Google search was used to find e-learning modules on the Web. RESULTS:
      The literature search resulted in 448 papers, of which none met the inclusion
      criteria of this study. The Google search resulted in 130 hits, of which 23 met
      the inclusion criteria of this review. Organizations that owned the modules were
      contacted, of which 13 responded and nine were included in this study. The
      effectiveness of two e-learning modules is currently being tested in a randomized
      controlled trial (RCT), one organization is planning to test the effectiveness of
      their module, and one organization has compared their face-to-face training with
      their online training. Furthermore, the included modules have different
      characteristics. CONCLUSION: There is a need for RCTs to study the effectiveness
      of online modules in this area and to understand which characteristics are
      essential to create effective e-learning modules to educate gatekeepers in
      suicide prevention.

PMID- 24901057
TI  - Suicide in Israel--an update.

PMID- 24901056
TI  - CT45A1 acts as a new proto-oncogene to trigger tumorigenesis and cancer
      metastasis.
AB  - Cancer/testis antigen (CTA)-45 family (CT45) belongs to a new family of genes in
      phylogenetics and is absent in normal tissues except for testis, but is
      aberrantly overexpressed in various cancer types. Whether CT45 and other CTAs act
      as proto-oncogenes has not been determined. Using breast cancer as a model, we
      found that CT45A1, a representative CT45 family member, alone had a weak
      tumorigenic effect. However, its neoplastic potency was greatly enhanced in the
      presence of growth factors. Overexpression of CT45A1 in breast cancer cells
      markedly upregulated various oncogenic and metastatic genes, constitutively
      activated ERK and CREB signaling pathways, promoted epithelial-mesenchymal
      transition, and increased cell stemness, tumorigenesis, invasion, and metastasis,
      whereas silencing CT45A1 significantly reduced cancer cell migration and
      invasion. We propose that CT45A1 functions as a novel proto-oncogene to trigger
      oncogenesis and metastasis. CT45A1 and other CT45 members are therefore excellent
      targets for anticancer drug discovery and targeted tumor therapy, and valuable
      genes in the study of a molecular phylogenetic tree. 

PMID- 24901059
TI  - Preliminary results from an examination of episodic planning in suicidal
      behavior.
AB  - BACKGROUND: Prior research has reported that a substantial portion of suicidal
      behavior occurs impulsively. These studies, however, have been unable to assess
      for episodic planning. AIMS: To provide preliminary support for the plausibility
      and utility of assessing episodic, nonlinear planning in suicidal behavior.
      METHOD: Fifty undergraduates with a prior history of suicidal behavior responded
      to a series of questions assessing level of attempt, method, and level of
      planning during their most recent self-reported suicide attempt. RESULTS: Level
      of intent was positively associated with planning, and the modal individual whose
      most recent attempt involved clear intent to die endorsed planning for at least 1
      year. CONCLUSION: These preliminary data support the plausibility and potential
      utility of assessing episodic planning and indicate that suicide attempts
      involving a clear intent to die typically require extensive levels of planning
      and rarely (if ever) emerge without forethought.

PMID- 24901060
TI  - A CBT-based psychoeducational intervention for suicide survivors: a cluster
      randomized controlled study.
AB  - BACKGROUND: Bereavement following suicide is associated with an increased
      vulnerability for depression, complicated grief, suicidal ideation, and suicide.
      There is, however, a paucity of studies of the effects of interventions in
      suicide survivors. AIMS: This study therefore examined the effects of a cognitive
      behavioral therapy (CBT)-based psychoeducational intervention on depression,
      complicated grief, and suicide risk factors in suicide survivors. METHOD: In
      total, 83 suicide survivors were randomized to the intervention or the control
      condition in a cluster randomized controlled trial. Primary outcome measures
      included maladaptive grief reactions, depression, suicidal ideation, and
      hopelessness. Secondary outcome measures included grief-related cognitions and
      coping styles. RESULTS: There was no significant effect of the intervention on
      the outcome measures. However, the intensity of symptoms of grief, depressive
      symptoms, and passive coping styles decreased significantly in the intervention
      group but not in the control group. CONCLUSION: The CBT-based psychoeducational
      intervention has no significant effect on the development of complicated grief
      reactions, depression, and suicide risk factors among suicide survivors. The
      intervention may, however, serve as supportive counseling for suicide survivors.

PMID- 24901063
TI  - Mapping environmental partitioning properties of nonpolar complex mixtures by use
      of GC * GC.
AB  - Comprehensive two-dimensional gas chromatography (GC * GC) is effective for
      separating and quantifying nonpolar organic chemicals in complex mixtures. Here
      we present a model to estimate 11 environmental partitioning properties for
      nonpolar analytes based on GC * GC chromatogram retention time information. The
      considered partitioning properties span several phases including pure liquid,
      air, water, octanol, hexadecane, particle natural organic matter, dissolved
      organic matter, and organism lipids. The model training set and test sets are
      based on a literature compilation of 648 individual experimental partitioning
      property data. For a test set of 50 nonpolar environmental contaminants,
      predicted partition coefficients exhibit root-mean-squared errors ranging from
      0.19 to 0.48 log unit, outperforming Abraham-type solvation models for the same
      chemical set. The approach is applicable to nonpolar organic chemicals containing
      C, H, F, Cl, Br, and I, having boiling points <=402  degrees C. The presented
      model is calibrated, easy to apply, and requires the user only to identify a
      small set of known analytes that adapt the model to the GC * GC instrument
      program. The analyst can thus map partitioning property estimates onto GC * GC
      chromatograms of complex mixtures. For example, analyzed nonpolar chemicals can
      be screened for long-range transport potential, aquatic bioaccumulation
      potential, arctic contamination potential, and other characteristic partitioning
      behaviors. 

PMID- 24901061
TI  - Measuring trainer fidelity in the transfer of suicide prevention training.
AB  - BACKGROUND: Finding effective and efficient models to train large numbers of
      suicide prevention interventionists, including 'hotline' crisis counselors, is a
      high priority. Train-the-trainer (TTT) models are widely used but understudied.
      AIMS: To assess the extent to which trainers following TTT delivered the Applied
      Suicide Intervention Skills Training (ASIST) program with fidelity, and to
      examine fidelity across two trainings and seven training segments. METHOD: We
      recorded and reliably rated trainer fidelity, defined as adherence to program
      content and competence of program delivery, for 34 newly trained ASIST trainers
      delivering the program to crisis center staff on two separate occasions. A total
      of 324 observations were coded. Trainer demographics were also collected.
      RESULTS: On average, trainers delivered two-thirds of the program. Previous
      training was associated with lower levels of trainer adherence to the program. In
      all, 18% of trainers' observations were rated as solidly competent. Trainers did
      not improve fidelity from their first to second training. Significantly higher
      fidelity was found for lectures and lower fidelity was found for interactive
      training activities including asking about suicide and creating a safe plan.
      CONCLUSIONS: We found wide variability in trainer fidelity to the ASIST program
      following TTT and few trainers had high levels of both adherence and competence.
      More research is needed to examine the cost-effectiveness of TTT models.

PMID- 24901065
TI  - Quantum dots and graphene oxide fluorescent switch based multivariate testing
      strategy for reliable detection of Listeria monocytogenes.
AB  - Graphene oxide (GO) and quantum dots (QDs), as burgeoning types of nanomaterials,
      have gained tremendous interest in the biosensor field. In this work, we designed
      a novel multivariate testing strategy that depends on the fluorescence resonance
      energy transfer (FRET) effect between quantum dots (QDs) and graphene oxide (GO).
      It integrates the QD-GO FRET principle and QD probes with different emission
      peaks into a platform, aims at multiplex gene detection of a human infectious and
      highly pathogenic pathogen, Listeria monocytogenes (L. monocytogenes). With the
      development of a multiplex linear-after-the-exponential (LATE) polymerase chain
      reaction (PCR) system, the single-stranded DNA (ssDNA) products of hlyA genes and
      iap genes are obtained by simultaneous amplification of the target genes. Then
      with the hybridization of ssDNA products and QD probes, simultaneous homogeneous
      detection of two gene amplification products can be achieved by using GO as a
      fluorescence switch and monitoring the relevant emissions excited by a single
      light source. Distinguishable signals corresponding to target genes are obtained.
      With this developed approach, genomic DNA from L. monocytogenes can be detected
      as low as 100 fg/MUL. Moreover, this platform has a good dynamic range from 10(2)
      to 10(6) fg/MUL. It is indicated that this platform has potential to be a
      reliable complement for rapid gene detection technologies and is capable of
      reducing the false-negative and false-dismissal probabilities in routine tests. 

PMID- 24901064
TI  - Covert thermal barcodes based on phase change nanoparticles.
AB  - An unmet need is to develop covert barcodes that can be used to track-trace
      objects, and authenticate documents. This paper describes a new nanoparticle
      based covert barcode system, in which a selected panel of solid-to-liquid phase
      change nanoparticles with discrete and sharp melting peaks is added in a variety
      of objects such as explosive derivative, drug, polymer, and ink. This method has
      high labeling capacity owing to the small sizes of nanoparticles, sharp melting
      peaks, and large scan range of thermal analysis. The thermal barcode can enhance
      forensic investigation by its technical readiness, structural covertness, and
      robustness. 

PMID- 24901066
TI  - Stress distribution in the temporomandibular joint after mandibular protraction:
      a three-dimensional finite element study.
AB  - OBJECTIVE: To evaluate the stress patterns in temporomandibular joint (TMJ)
      during mandibular protraction at different horizontal advancements with constant
      vertical height in a construction bite using a three-dimensional finite element
      method. MATERIALS AND METHODS: A three-dimensional computer-aided model was
      developed from the magnetic resonance imaging (MRI) of a growing boy (age 12
      years) using MIMICS software (version 7.0, Materialise, Leuven, Belgium).
      Stresses with constant vertical opening of 5 mm changing the sagittal
      advancements from 0 mm to 5 mm and 7.5 mm were recorded. Differences in magnitude
      and pattern of stresses were compared. RESULTS: The tensile stresses in the
      posterosuperior aspect of the condylar head and on the posterior aspect of the
      glenoid fossa migrated posteriorly with increased bite advancements. The location
      of tensile stresses changed in the condylar head and fossa on mandibular
      protraction of 5 mm to 7 mm. CONCLUSION: This study indicates that larger
      horizontal advancements of construction bites may not be favorable for tissues of
      TMJ. Clinical application necessitates study on an animal model.

PMID- 24901067
TI  - Contemporary esthetic nickel-titanium wires: do they deliver the same forces?
AB  - OBJECTIVE: To test for differences in loading and unloading forces delivered by
      six coated nickel-titanium wires and their noncoated equivalents. MATERIALS AND
      METHODS: From six commercial companies, 0.016-inch diameter round and 0.016 *
      0.022-inch rectangular cross-section nickel-titanium wires were procured "as is":
      Rocky Mountain Orthodontics (Denver, Colo), TP Orthodontics (La Porte, Ind),
      American Orthodontics (AO; Sheboygan, Wis), G&H (Franklin, Ind), Opal
      Orthodontics (South Jordan, Utah), and Forestadent USA (St Louis, Mo) (round
      only). The wires were evaluated using a three-point bending test based on the
      method in ISO Standard 15841. RESULTS: No statistically significant differences
      (P > .05) in force values were found between coated and noncoated wires, listed
      by deflection in three-point bending, for these specific groups: 1 mm, TP round;
      2 mm, TP round and G&H rectangular; 3 mm, G&H round and G&H rectangular; 2.5
      mm,TP round and G&H rectangular; 1.5 mm, TP round, G&H round, G&H rectangular,
      and AO rectangular; and 0.5 mm, AO rectangular and G&H round. CONCLUSION: Some
      manufacturers market esthetic wires delivering forces similar to the equivalent
      noncoated wires, when tested according to a standard three-point bend method.

PMID- 24901068
TI  - Absence of multiple premolars and ankylosis of deciduous molar with cant of the
      occlusal plane treated using skeletal anchorage.
AB  - Ankylosis and the absence of premolars are two relatively common conditions
      encountered in the field of orthodontics. However, the absence of multiple
      premolars, particularly two adjacent premolars, along with ankylosis of deciduous
      teeth, is unusual. Herein, we present a case report and discuss some aspects
      related to these abnormalities. A 15-year-old boy was missing the upper right
      first and second premolars and the lower right and left second premolars. In
      addition, the deciduous lower left second molar was ankylosed and in
      infraocclusion, causing canting of the occlusal plane. The patient was treated
      with a mini-implant to correct the Class II malocclusion on the left side and a
      miniplate to correct the cant of the occlusal plan. After treatment, the upper
      right space was kept closed, with the canine in contact with the first molar, and
      the lower left space was opened to an implant-prosthetic rehabilitation.

PMID- 24901069
TI  - An investigation of possible competing mechanisms for Ni-containing methyl
      coenzyme M reductase.
AB  - Ni-containing methyl-coenzyme M reductase (MCR) is capable of catalyzing methane
      formation from methyl-coenzyme M (CH3-SCoM) and coenzyme B (CoB-SH), and also its
      reverse reaction (methane oxidation). Based on extensive experimental and
      theoretical investigations, it has turned out that a mechanism including an
      organometallic methyl-Ni(III)F430 intermediate is inaccessible, while another
      mechanism involving a methyl radical and a Ni(II)-SCoM species currently appears
      to be the most acceptable one for MCR. In the present paper, using hybrid density
      functional theory and an active-site model based on the X-ray crystal structure,
      two other mechanisms were studied and finally also ruled out. One of them,
      involving proton binding on the CH3-SCoM substrate, which should facilitate
      methyl-Ni(III)F430 formation, is demonstrated to be quite unfavorable since the
      substrate has a much smaller proton affinity than the F430 cofactor. Another one
      (oxidative addition mechanism) is also shown to be unfavorable for the MCR
      reaction, due to the large endothermicity for the formation of the ternary
      intermediate with side-on C-S (for CH3-SCoM) or C-H (for methane) coordination to
      Ni.

PMID- 24901070
TI  - Supramolecular control of a mononuclear biomimetic copper(II) center: bowl
      complexes vs funnel complexes.
AB  - Modeling the mononuclear site of copper enzymes is important for a better
      understanding of the factors controlling the reactivity of the metal center. A
      major difficulty stems from the difficult control of the nuclearity while
      maintaining free sites open to coordination of exogenous ligands. A
      supramolecular approach consists in associating a hydrophobic cavity to a
      tripodal ligand that will define the coordination spheres as well as access to
      the metal ion. Here, we describe the synthesis of a bowl Cu(II) complex based on
      the resorcinarene scaffold. This study supplements a previous work on Cu(I)
      coordination. It provides a complete picture of the cavity-copper system in its
      two oxidation states. The first XRD structure of such a bowl complex was
      obtained, evidencing a 5-coordinate Cu(II) ion with the three imidazole donors
      bound to the metal (two in the base of the pyramid, one in the apical position)
      and with an acetate anion, completing the base of the pyramid, and deeply
      included in the bowl. Solution studies conducted by EPR and UV-vis absorption
      spectroscopies as well as cyclic voltammetry highlighted interaction with
      coordinating solvents, various carboxylates that can sit either in the endo or in
      the exo position depending on their size as well as possible stabilization of
      hydroxo species in a mononuclear state. A comparison of the binding and redox
      properties of the bowl complex with funnel complexes based on the calix[6]arene
      core further highlights the importance of supramolecular features defining the
      first, second, and third coordination sphere for control of the metal ion. 

PMID- 24901071
TI  - Hysteretic adsorption of CO2 onto a Cu2(pzdc)2(bpy) porous coordination polymer
      and concomitant framework distortion.
AB  - The present study focuses on the long-range structural changes that occur in the
      porous coordination polymer Cu2(pzdc)2(bpy) (pzdc = pyrazine-2,3-dicarboxylate,
      bpy = 4,4'-bipyridine), also known as CPL-2, upon adsorption of CO2 at 25 
      degrees C and up to 7 atm. The structural data were gathered using in situ
      diffraction studies. CPL-2 exhibited an unexpected hysteretic adsorption
      desorption process. The onset of hysteresis occurs at a pressure where full
      occupancy of the volume of the CPL-2 galleries is achieved while the framework
      retains a structure similar to what is observed under ambient conditions.
      Moreover, the onset occurs at a CO2 partial pressure larger than 2 atm and could
      be related to a combination of adsorbate-adsorbent interactions and forces
      exerted onto the CPL-2 framework. Pore volumes estimated from fits of the Dubinin
      Astakhov isotherm model against the CO2 desorption data gathered at 25 and -78.5 
      degrees C, respectively, provided further evidence of the aforementioned CPL-2
      framework changes. These findings are of relevance to the understanding of
      adsorption processes in metal organic frameworks or coordination polymers under
      conditions that are of relevance to gas capture at industrial scale. 

PMID- 24901072
TI  - The human Cathelicidin LL-37 induces MUC5AC mucin production by airway epithelial
      cells via TACE-TGF-alpha-EGFR pathway.
AB  - AIM: To investigate the mechanism for LL-37 inducing MUC5AC mucin production in
      airway epithelial cells. MATERIALS AND METHODS: The airway epithelial NCI-H292
      cells were stimulated with various concentrations of LL-37 synthetic peptide and
      scrambled LL-37 (sLL-37) synthetic peptide ranged from 2.5 to 10 MUg/mL. The
      effects of LL-37 and sLL-37 on TNF-alpha-converting enzyme (TACE) and EGFR
      activation and MUC5AC mucin production were evaluated by fluorescence resonance
      energy transfer (FRET) assay, Western blotting and ELISA respectively.
      Furthermore, we measured changes of transforming growth factor-alpha (TGF-alpha)
      in culture supernatants. A serious of inhibitors including TACE inhibitor TAPI-1,
      EGFR inhibitor AG1478, EGFR-neutralizing antibody, TGF-alpha-neutralizing
      antibody, amphiregulin (AR)-neutralizing antibody, and heparin binding-epidermal
      growth factor (HB-EGF)-neutralizing antibody were used to block the signaling
      pathway. Human serum and FBS were also used to investigate the effects of serum
      on LL-37-induced MUC5AC mucin production. RESULTS: LL-37 induced TACE and EGFR
      activation, as well as TGF-alpha and MUC5AC mucin production by NCI-H292 cells in
      a dose-dependent manner. EGFR-neutralizing antibody and AG1478 inhibited LL-37
      induced EGFR activation and subsequent MUC5AC mucin production, whereas TGF-alpha
      neutralizing antibody increased LL-37-induced TGF-alpha production. TAPI-1
      inhibited LL-37-induced TGF-alpha production, EGFR activation and subsequent
      MUC5AC mucin production, whereas TGF-alpha-neutralizing antibody, but not AR- or
      HB-EGF-neutralizing antibody, inhibited LL-37-induced EGFR activation and
      subsequent MUC5AC mucin production in NCI-H292 cells. The sLL-37 had no effect on
      TACE and EGFR activation and MUC5AC mucin production. Additionally, Human serum,
      rather than FBS, inhibited LL-37-induced MUC5AC mucin production. CONCLUSIONS: LL
      37 induces MUC5AC mucin production by airway epithelial cells via TACE-TGF-alpha
      EGFR pathway.

PMID- 24901073
TI  - Target-controlled formation of silver nanoclusters in abasic site-incorporated
      duplex DNA for label-free fluorescence detection of theophylline.
AB  - A novel, label-free, fluorescence based sensor for theophylline has been
      developed. In the new sensor system, an abasic site-incorporated duplex DNA probe
      serves as both a pocket for recognition of theophylline and a template for the
      preparation of fluorescent silver nanoclusters. The strategy relies on
      theophylline-controlled formation of fluorescent silver nanoclusters from abasic
      site-incorporated duplex DNA. When theophylline is not present, silver ions
      interact with the cytosine groups opposite to the abasic site in duplex DNA. This
      interaction leads to efficient formation of intensely red fluorescent silver
      nanoclusters. In contrast, when theophylline is bound at the abasic site through
      pseudo base-pairing with appropriately positioned cytosines, silver ion binding
      to the cytosine nucleobase is prevented. Consequently, fluorescent silver
      nanoclusters are not formed causing a significant reduction of the fluorescence
      signal. By employing this new sensor, theophylline can be highly selectively
      detected at a concentration as low as 1.8 MUM. Finally, the diagnostic capability
      and practical application of this sensor were demonstrated by its use in
      detecting theophylline in human blood serum. 

PMID- 24901074
TI  - The interplay between sympathetic overactivity, hypertension and heart rate
      variability (review, invited).
AB  - The control of arterial pressure is a complex interaction of the long- and short
      term influences of hormones, local vascular factors, and neural mechanisms. The
      autonomic nervous system and its sympathetic arm play important roles in the
      regulation of blood pressure, and overactivity of sympathetic nerves may have an
      important role in the development of hypertension and related cardiovascular
      disorders. The baroreceptor system opposes either increases or decreases in
      arterial pressure, and the primary purpose of the arterial baroreflex is to keep
      blood pressure close to a particular set point over a relatively short period of
      time. The ability of the baroreflex to powerfully buffer acute changes in
      arterial pressure is well established, but the role of the arterial baroreceptor
      reflex in long-term control of arterial pressure has been a topic of many debate
      and controversy for decades. The sympathetic nervous system and arterial
      baroreceptor reflex control of renal sympathetic nerve activity has been proposed
      to play a role in long-term control of arterial pressure. The aim of this paper
      has been to review the postulated role of sympathetic activation. 

PMID- 24901075
TI  - Oscillation in O2 uptake in impulse exercise.
AB  - The purpose of the present study was to examine 1) whether O(2) uptake (VO(2))
      oscillates during light exercise and 2) whether the oscillation is enhanced after
      impulse exercise. After resting for 1 min on a bicycle seat, subjects performed 5
      min pre-exercise with 25 watts work load, 10-s impulse exercise with 200 watts
      work load and 15-min post exercise with 25 watts work load at 80 rpm. VO(2)
      during pre-exercise significantly increased during impulse exercise and suddenly
      decreased and re-increased until 23 s after impulse exercise. In the cross
      correlation between heart rate (HR) and VO(2) after impulse exercise, VO(2)
      strongly correlated to HR with a time delay of -4 s. Peak of power spectral
      density (PSD) in HR appeared at 0.0039 Hz and peak of PSD in VO(2) appeared at
      0.019 Hz. The peak of the cross power spectrum between VO(2) and HR appeared at
      0.0078 Hz. The results suggested that there is an oscillation in O(2) uptake
      during light exercise that is associated with the oscillation in O(2) consumption
      in active muscle. The oscillation is enhanced not only by change in O(2)
      consumption but also by O(2) content transported from active muscle to the lungs.

PMID- 24901076
TI  - Muscle damage after low-intensity eccentric contractions with blood flow
      restriction.
AB  - Discrepancies exist whether blood flow restriction (BFR) exacerbates exercise
      induced muscle damage (EIMD). This study compared low-intensity eccentric
      contractions of the elbow flexors with and without BFR for changes in indirect
      markers of muscle damage. Nine untrained young men (18-26 y) performed low
      intensity (30% 1RM) eccentric contractions (2-s) of the elbow flexors with one
      arm assigned to BFR and the other arm without BFR. EIMD markers of maximum
      voluntary isometric contraction (MVC) torque, range of motion (ROM), upper arm
      circumference, muscle thickness and muscle soreness were measured before,
      immediately after, 1, 2, 3, and 4 days after exercise. Electromyography (EMG)
      amplitude of the biceps brachii and brachioradialis were recorded during
      exercise. EMG amplitude was not significantly different between arms and did not
      significantly change from set 1 to set 4 for the biceps brachii but increased for
      the brachioradialis (p <= 0.05, 12.0% to 14.5%) when the conditions were
      combined. No significant differences in the changes in any variables were found
      between arms. MVC torque decreased 7% immediately post-exercise (p <= 0.05), but
      no significant changes in ROM, circumference, muscle thickness and muscle
      soreness were found. These results show that BFR does not affect EIMD by low
      intensity eccentric contractions. 

PMID- 24901077
TI  - Blood flow restriction: effects of cuff type on fatigue and perceptual responses
      to resistance exercise.
AB  - Blood flow restriction (BFR) combined with low load resistance training has been
      shown to result in muscle hypertrophy similar to that observed with higher loads.
      However, not all studies have found BFR efficacious, possibly due to
      methodological differences. It is presently unclear whether there are differences
      between cuffs of similar size (5 cm) but different material (nylon vs. elastic).
      The purpose was to determine if there are differences in repetitions to fatigue
      and perceptual ratings of exertion (RPE) and discomfort between narrow elastic
      and narrow nylon cuffs. Sixteen males and females completed three sets of BFR
      knee extension exercise in a randomized cross-over design using either elastic or
      nylon restrictive cuffs applied at the proximal thigh. There were no differences
      in repetitions to fatigue (marker of blood flow) or perceptual ratings between
      narrow elastic and narrow nylon cuffs. This data suggests that either elastic or
      nylon cuffs of the same width should cause similar degrees of BFR at the same
      pressure during resistance exercise. 

PMID- 24901078
TI  - A possible genetic influence in parenchyma and small airway changes in COPD: a
      pilot study of twins using HRCT.
AB  - Genetic effects that contribute to the risk of developing chronic obstructive
      pulmonary disease (COPD) have been reported. Our purpose was to estimate the
      possible genetic influence on CT features related to COPD in twins. METHODS: Two
      COPD-discordant and one COPD-concordant monozygotic (MZ) twin pair, in addition
      to 2 control dizygotic (DZ) twin pairs underwent a low-dose high resolution
      computer tomography (HRCT) in inspiration and expiration (Philips Brilliance 16).
      RESULTS: Monozygotic twins were more similar in lung volume expiration and in air
      trapping score compared to dizygotics (382 cm(3) vs. 2303 cm(3) and 17.6% vs.
      26.6%, respectively). In general, MZ twin pairs showed almost identical HRCT
      features independently of smoking attitude and COPD status. The dizygotic twin
      pairs showed larger differences in HRCT features compared to MZ twins.
      CONCLUSIONS: Lung parenchymal and small airway changes (lung density, presence of
      bronchial wall thickening, bronchiectasis and/or mucus plug formation, air
      trapping and emphysema score) seem to be genetically associated traits,
      independently of smoking/COPD history. A future study with a larger sample size
      should confirm our findings.

PMID- 24901079
TI  - GNB3 gene c.825C>T polymorphism and performance parameters in professional
      basketball players.
AB  - This study has been conducted to determine whether mean values of peak oxygen
      consumption (VO(2peak)), anaerobic test parameters and knee isokinetic test
      measurements are different among guanine nucleotide-binding protein, beta-3
      (GNB3) genotype groups in a group of basketball players. METHODS: Seventy-two
      healthy male (mean age, 22.9 +/- 5.3 years) basketball players from the first
      division of national league participated. We studied GNB3 gene c.825C>T (rs5443)
      polymorphism, then divided the subjects into three groups as CC (n = 21), CT (n =
      35), and TT (n =1 6). Mean VO(2peak), Wingate anaerobic test results, and
      isokinetic knee muscle strength measurements were compared among the genotype
      groups. RESULTS: Mean VO(2peak) (60.1 +/- 3.9; 56.7 +/- 3.6; and 57.8 +/- 3.3,
      respectively, p < 0.01), mean anaerobic minimum power (5.1 +/- 0.4; 5.3 +/- 0.5;
      and 4.4 v 0.5 W/kg, respectively, p < 0.001), mean anaerobic power drop (57.0 +/-
      6.2; 54.2 +/- 6.9; and 62.9 +/- 5.3%, respectively, p < 0.001) were significantly
      different among the study groups, CC, CT, and TT. Individuals with TT genotype
      exerted lower performance in terms of isokinetic knee muscle strength.
      CONCLUSION: The presence of 825T-allele may impair athletic performance and may
      serve as a genetic marker of low capacity for athletic performance in male
      basketball players.

PMID- 24901080
TI  - Metabolic and ventilatory effects of oral glucose load at rest and during
      incremental aerobic muscular work in young healthy adults.
AB  - We measured respiratory ratio (RR), pulmonary ventilation (VE) and end-tidal
      carbon dioxide partial pressure (ETPCO2) at rest and during cycling aerobic
      workloads (20%, 40%, 60% of estimated maximal oxygen uptake). Measurements were
      taken after overnight fasting and after an oral glucose load. RR, VE and ETPCO2
      increased with workload. Glucose load caused RR and VE increments at rest (0.75
      +/- 0.01 vs. 0.86 +/- 0.02, p < 0.01, and 10.8 +/- 0.43 vs. 12.1 +/- 0.49 l/min,
      p < 0.01, respectively) and for each workload (20% estimated maximal oxygen
      uptake: 0.77 +/- 0.01 vs. 0.855 +/- 0.02, p < 0.01, and 16.2 +/- 0.73 vs. 17.7 +/
      0.8 l/min, p < 0.01; 40% estimated maximal oxygen uptake: 0.76 +/- 0.02 vs. 0.82
      +/- 0.01, p < 0.01, and 25.9 +/- 1.1 vs. 28.3 +/- 1.3 l/min, p < 0.05; 60%
      estimated maximal oxygen uptake: 0.85 +/- 0.02 vs. 0.91 +/- 0.02, p < 0.01, and
      37.4 +/- 1.7 vs. 40.9 +/- 1.9 l/min, p < 0.05) but ETPCO2 did not change. The
      differences in RR before and after glucose load became smaller as the workload
      increased. Linear regression analysis of VE and carbon dioxide output yielded
      virtually identical results for both fasting and glucose load conditions. We have
      concluded that: a) for the metabolic carbon dioxide load increment due to glucose
      induced RR increment, the physiological response is an increase of VE at all
      workloads. This response modulates constant ETPCO2 values; b) on workload
      increment, skeletal muscle increasingly utilises more and more glycogen stores,
      regardless of the blood glucose availability. This reduces the usefulness of
      dietary manipulations decreasing carbon dioxide metabolic load during muscular
      work in respiratory failure; c) the absolute value of metabolic carbon dioxide
      load exerts a role in ventilation regulation at rest and during aerobic exercise.

PMID- 24901081
TI  - The relationship between the metabolic syndrome and its components and bone
      status in postmenopausal women.
AB  - The association between metabolic syndrome (MS) and bone status remains
      controversial. We aimed to study the relationships between MS, bone mineral
      density (BMD), and bone metabolism in postmenopausal women. MATERIAL AND METHODS:
      MS was assessed in 218 white postmenopausal women. BMD (lumbar spine and hip) was
      measured by dual energy X-ray absorptiometry (DXA). Serum carboxyterminal cross
      linked telopeptide of type 1 collagen (CTX), undercarboxylated osteocalcin (uOC),
      bone alkaline phosphate (BAP) and vitamin D were assayed. RESULTS: Postmenopausal
      women with MS had a significantly higher lumber spine BMD than women without MS
      (p < 0.05). A progressive increase of the BMD at both sites with the number of MS
      components was observed. Bone turnover markers and vitamin D levels were not
      significantly influenced by the presence of MS. BMD at both sites positively
      correlated with body mass index (BMI), waist circumference (WC) and glucose in
      unadjusted analysis. In multiple regression analysis, WC was independently
      associated with BMD at both sites, while hypertension was associated only with
      lumbar spine BMD. CONCLUSIONS: In postmenopausal women, MS is associated with
      increased lumbar spine BMD and this relation is explained mainly by the higher
      BMI and WC in the MS group.

PMID- 24901082
TI  - Effects of local anesthetics on contractions of pregnant and non-pregnant rat
      myometrium in vitro.
AB  - In order to determine whether local anesthetics directly affect the propagation
      and strength of myometrial contractions, we compared the effects of bupivacaine,
      ropivacaine, lidocaine and tetracaine on the contractions of myometrium isolated
      from pregnant and non-pregnant rats. Full-thickness myometrial strips were
      obtained from 18- to 21-day pregnant and non-pregnant Sprague-Dawley rats and
      incubated in an organ bath. When spontaneous contractions became regular, strips
      were exposed to cumulative concentrations of the four local anesthetics ranging
      from 0.01 to 300 MUmol/L and the amplitude and frequency of contraction were
      recorded. All four compounds caused a concentration-dependent inhibition of the
      contractility of pregnant and non-pregnant uterine muscle. In pregnant
      myometrium, the concentration that caused 50% inhibition (IC(50)) was 100 MUmol/L
      for bupivacaine, 157 MUmol/L for ropivacaine, > 1000 MUmol/L for lidocaine, and
      26.3 MUmol/L for tetracaine. In non-pregnant myometrium, the IC(50) was 26.9
      MUmol/L for bupivacaine, 40 MUmol/L for ropivacaine, 384 MUmol/L for lidocaine,
      and 7.4 MUmol/L for tetracaine. These results suggested that local anesthetics do
      inhibit myometrial contractions in pregnant and non-pregnant rats in a
      concentration-dependent manner.

PMID- 24901083
TI  - Physiological response is similar in overweight and normoweight boys during
      cycling: a longitudinal study.
AB  - The purpose of this study was to determine whether metabolic cost is similar in
      overweight and normoweight children when workload during exercise on a cycle
      ergometer is adjusted relative to an objectively determined second ventilatory
      threshold (VT2) or the maximal workload (Pmax). The tests were conducted every 2
      years: first at the age of 10 years and the third test at around the age of 14
      years. The levels of maximal oxygen consumption (VO(2)max), Pmax, and the VT2
      were determined by means of graded tests on a cycle ergometer. The main test
      consisted of two 6-minute exercises of submaximal constant intensity (below and
      above VT2) performed on a cycle ergometer, with a 4-minute recovery between
      efforts. The workload during cycling was adjusted individually for each
      participant and adjusted to the values determined in the graded test: workload at
      VT2 and Pmax. Physiological response (absolute and relative to free-fat mass
      oxygen uptake, heart rate, pulmonary ventilation, tidal volume, and breathing
      frequency) is similar in overweight and normoweight boys when workload on a cycle
      ergometer is adjusted to VT2. The only significant intergroup difference was seen
      in relative to body mass oxygen intake.

PMID- 24901084
TI  - A comparative study on dyslipidaemia inducing diets in various rat strains.
AB  - In our experiments we compared the serum lipoprotein lipid composition of Fischer
      344 (F344) and Long-Evans (LE) inbred rats as well as of their hybrid FLF(1) from
      both sexes after feeding them for 2, 4 and 8 weeks with different diets. The
      following diets were used: 1) standard diet marked as CRLT/N; 2) diet reach in
      butter marked as BR; 3) diet containing cholesterol, sodium cholate and
      methylthiouracil marked as CR; 4) diet marked as BRC, which is the Hartroft-Sos
      diet modified by our research group consisting of the diets BR and CR. The latter
      diet was the most effective, because within two weeks the level of serum total
      cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride in the F344 female
      rats increased 8, 30, 4 and 8 times, respectively. The male rats of the Long
      Evans strain showed moderately increased values while the FLF(1) female hybrids
      derived from the hybridization of LE males and F344 females had values closer to
      those of the mother strain. Despite the fact that during this time the LDL/HDL
      ratio increased from 0.06 to 2.97 and the PON-1 activity decreased to one-third,
      a significant lipid deposition could not be shown in the wall of the abdominal
      aorta even two months later. Our experimental model is suitable for the
      chemoprevention of dyslipidaemia or rapid testing of molecules chosen for its
      treatment.

PMID- 24901085
TI  - A short commentary on Aristotle's scientific legacy and his definition of the
      physiologist.
AB  - The roots of physiology - on the basis of a systematic study of the human body's
      functions and their correlation to anatomy - date back to the works of Aristotle.
      The pupil of Plato and the tutor of Alexander the Great was a one-man university,
      and his contributions to the medical sciences have been immense. His surviving
      works highlight the first serious approach towards the rejection of metaphysical
      and mythological thought, and have: (i) demonstrated a deep appreciation for a
      systematic, non-metaphysical study of the natural world, (ii) set the foundations
      of comparative and human anatomy, (iii) established the first (indirect)
      definition of the "physiologist", and (iv) exercised a dominant influence upon
      the subsequent history of Hellenistic, European and Arabic Medicine. The current
      letter provides a short commentary on the historical account of Physiology as a
      scientific field and underlines the unique legacy that Aristotle has provided us
      with. 

PMID- 24901086
TI  - The association between the built environment and dietary intake - a systematic
      review.
AB  - We reviewed the literature that examines the association between the built
      environment and diet. The MEDLINE electronic database was searched. Eligible
      articles must have been published between 2000 and 2013, in the English language,
      and must have been conducted among a population-based sample of adults older than
      18 years of age. Twenty-four articles met the inclusion criteria. The majority of
      studies (over 70%) focused on fruit and vegetable consumption. Most studies (88%)
      found a statistically significant relationship between diet and some aspect of
      the built environment. However, the results across studies were not consistent.
      These inconsistencies may be attributable to methodological challenges, including
      differing definitions of neighbourhood, and inconsistent approaches to measuring
      built environment features and diet. In order to explore the complex relationship
      between built environment and people's dietary behaviour, research design needs
      to be improved, and the items people actually buy need to be examined. In
      addition, more research is needed to investigate the causal pathways linking
      environmental factors and dietary intake. 

PMID- 24901087
TI  - Comparison of measured and predicted energy expenditure in patients with liver
      cirrhosis.
AB  - Obesity is a risk factor for the onset of liver cancer in patients with
      cirrhosis. To prevent overfeeding and obesity, estimation of energy requirement
      is important, but energy expenditure in patients with liver cirrhosis has not
      been fully elucidated. This study aimed to investigate resting energy expenditure
      (REE) and energy intake in patients with cirrhosis and determine adequate energy
      intake criteria. In this cross-sectional study, indirect calorimetry measurement
      was conducted in 488 Japanese inpatients with cirrhosis. We compared REE measured
      by indirect calorimetry (M-REE) with basal energy expenditure (BEE) predicted by
      the Harris-Benedict equation (H-BEE) and Dietary Reference Intakes (DRI) for
      Japanese (D-BEE). Mean M-REE (1256 kcal) was significantly lower than H-BEE (1279
      kcal); however, it was not significantly different from D-BEE (1254 kcal). Mean M
      REE expressed in relation to body weight (BW; REE/kg BW) was 21.7 kcal/kg BW. H
      BEE was significantly higher than M-REE in patients in the first and second
      quartiles of BMI, and D-BEE was significantly different from MREE in patients in
      the highest and lowest quartiles of BMI. Average energy intake was 30.5 kcal/kg
      BW, which was 1.4 times greater than REE/kg BW. Although DRI is a useful tool for
      the estimation of REE in patients in the second and third quartiles of BMI, M-REE
      is recommended to ensure the provision of adequate nutritional care to patients
      with cirrhosis, including those in the highest and lowest quartiles of BMI. 

PMID- 24901088
TI  - Urinary isoflavonoid excretion as a biomarker of dietary soy intake during two
      randomized soy trials.
AB  - We evaluated urinary isoflavonoid excretion as a biomarker of dietary isoflavone
      intake during two randomized soy trials (13-24 months) among 256 premenopausal
      women with a total of 1,385 repeated urine samples. Participants consumed a high
      soy diet (2 servings/day) and a low-soy diet (<3 servings/week), completed 7
      unannounced 24-hour dietary recalls, and donated repeated urine samples, which
      were analyzed for isoflavonoid excretion by liquid chromatography methods. We
      computed Spearman correlation coefficients and applied logistic regression to
      estimate the area under the curve. Median overall daily dietary isoflavone
      intakes at baseline, during low- and high-soy diet were 2.3, 0.2, and 60.4 mg
      aglycone equivalents, respectively. The corresponding urinary isoflavonoid
      excretion values were 0.4, 1.0, and 32.4 nmol/mg creatinine. Across diets,
      urinary isoflavonoid excretion was significantly associated with dietary
      isoflavone intake (rs=0.51, AUC=0.85; p<0.0001) but not within diet periods
      (rs=0.05-0.06, AUC=0.565-0.573). Urinary isoflavonoid excretion is an excellent
      biomarker to discriminate between low- and high-soy diets across populations, but
      the association with dietary isoflavone intake is weak when the range of soy
      intake is small. 

PMID- 24901089
TI  - The impact of soluble dietary fibre on gastric emptying, postprandial blood
      glucose and insulin in patients with type 2 diabetes.
AB  - Dietary fibre plays an important role in controlling postprandial glycemic and
      insulin response in diabetic patients. The intake of dietary fibre has been shown
      to delay the gastric emptying in healthy subjects. The relationship between
      gastric emptying and postprandial blood glucose in diabetic patients with fibre
      load liquids needs to be investigated. To investigate the impact of soluble
      dietary fibre (SDF) on gastric emptying, postprandial glycemic and insulin
      response in patients with type 2 diabetes. 30 patients with type 2 diabetes (DM)
      and 10 healthy subjects (HS) matched for gender and age were randomized to
      receive SDF-free liquid (500 mL, 500 Kcal) and isoenergetic SDF liquid (oat beta
      glucan 7.5 g, 500 mL, 500 Kcal) on two separate days based on a cross-over with 6
      day wash-out period. Gastric emptying was monitored by ultrasonography at
      intervals of 30 min for 2 hours. Fasting and postprandial blood was collected at
      intervals of 30-60 min for 180 min to determine plasma glucose and insulin.
      Proximal gastric emptying was delayed by SDF-treatment both in DM (p=0.001) and
      HS (p=0.037). SDF resulted in less output volume in the distal stomach in DM
      (p<0.05). SDF decreased postprandial glucose (p=0.001) and insulin (p=0.001) in
      DM subjects. Postprandial glucose (r=-0.547, p=0.047) and insulin (r=-0.566,
      p=0.004) were negatively correlated with distal emptying of SDF in DM subjects.
      Distal gastric emptying was delayed significantly in DM subjects with HbA1c
      levels >=6.5% (p=0.021) or with complications (p=0.011) by SDF, respectively. SDF
      improved postprandial glycaemia which was related to slowing of gastric emptying.

PMID- 24901090
TI  - Higher cadmium burden in coastal areas than in inland areas in Korea:
      implications for seafood intake.
AB  - This survey was initiated to examine possible coastal-inland differences in
      cadmium (Cd) burden in general Korean populations. In total, 268 healthy non
      smoking middle-aged women (30 to 49 years; 88 residents in 8 coastal areas and
      180 residents in 15 inland areas) participated in the study. They offered
      peripheral blood and spot urine samples so that cadmium in blood (Cd-B) and urine
      (Cd-U) were taken as exposure markers. Determination of Cd-B and Cd-U was carried
      out by graphite furnace atomic absorption spectrophotometry. With regard to Cd
      burden, geometric means for the coastal and inland residents were 1.70 and 1.72
      MUg/L for Cd-B, 1.54 and 1.00 MUg/L for Cd-U as observed (Cd-U), 2.59 and 1.81
      MUg/g creatinine for Cd-U as corrected for creatinine (Cd-Ucr), respectively. Cd
      U and Cd-Ucr were higher in the coastal areas than in inland areas. Reasons for
      higher Cd-U in the coastal areas than in the inland areas were are discussed in
      relation to major sources of Cd in daily life of the residents. Attention was
      paid to consumption of fish and shellfish in the coastal areas as major sources
      of dietary Cd intake. This study shows that Cd burdens were higher in coastal
      areas than in inland areas in Korea. 

PMID- 24901091
TI  - Parental body mass index is associated with adolescent overweight and obesity in
      Mashhad, Iran.
AB  - OBJECTIVE: This cross-sectional study was carried out to determine the prevalence
      of overweight and obesity among secondary school children aged 12 to 14 years in
      the city of Mashhad, Iran and its association with parental body mass index.
      METHODS: A total of 1189 secondary school children (579 males and 610 females)
      aged 12- 14 years old were selected through a stratified multistage random
      sampling. All adolescents were measured for weight and height. Household socio
      demographic information and parental weight and height were self-reported by
      parents. Adolescents were classified as overweight or obese based on BMI-for age
      Z-score. Multivariable logistic Regression (MLR) determined the relationship
      between parental BMI and adolescent overweight and obesity. RESULTS: The overall
      prevalence of overweight and obesity among secondary school children in Mashhad
      was 17.2% and 11.9%, respectively. A higher proportion of male (30.7%) than
      female (27.4%) children were overweight or obese. BMI of the children was
      significantly related to parental BMI (p<0.001), gender (p= 0.02), birth order
      (p<0.01), parents' education level (p<0.001), father's employment status
      (p<0.001), and family income (p<0.001). MLR showed that the father's BMI was
      significantly associated with male BMI (OR: 2.02) and female BMI (OR: 1.59),
      whereas the mother's BMI was significantly associated with female BMI only (OR:
      0.514). CONCLUSION: The high prevalence of overweight/obesity among the research
      population compared with previous studies in Iran could be related to the
      changing lifestyle of the population. The strong relationship with parental BMI
      was probably related to a combination of genetic and lifestyle factors.
      Strategies to address childhood obesity should consider the interaction of these
      factors.

PMID- 24901092
TI  - Acute interval exercise intensity does not affect appetite and nutrient
      preferences in overweight and obese males.
AB  - This study investigated the influence of two different intensities of acute
      interval exercise on food preferences and appetite sensations in overweight and
      obese men. Twelve overweight/obese males (age=29.0+/-4.1 years; BMI =29.1+/-2.4
      kg/m2) completed three exercise sessions: an initial graded exercise test, and
      two interval cycling sessions: moderate-(MIIT) and high-intensity (HIIT) interval
      exercise sessions on separate days in a counterbalanced order. The MIIT session
      involved cycling for 5-minute repetitions of alternate workloads 20% below and
      20% above maximal fat oxidation. The HIIT session consisted of cycling for
      alternate bouts of 15 seconds at 85% VO2max and 15 seconds unloaded recovery.
      Appetite sensations and food preferences were measured immediately before and
      after the exercise sessions using the Visual Analogue Scale and the Liking &
      Wanting experimental procedure. Results indicated that liking significantly
      increased and wanting significantly decreased in all food categories after both
      MIIT and HIIT. There were no differences between MIIT and HIIT on the effect on
      appetite sensations and Liking & Wanting. In conclusion, manipulating the
      intensity of acute interval exercise did not affect appetite and nutrient
      preferences. 

PMID- 24901093
TI  - Serum copper, zinc and risk factors for cardiovascular disease in community
      living Japanese elderly women.
AB  - BACKGROUND: Associations of copper (Cu) and zinc (Zn) serum levels with risk
      factors for cardiovascular disease (CVD) have not been extensively studied in
      elderly Asian people. METHODS: Relationships to CVD risk factors were examined in
      202 freely-living elderly Japanese women. RESULTS: By univariate analysis, log
      high-sensitivity C-reactive protein (hsCRP) and non-HDL cholesterol were
      associated with serum Cu concentrations. An independent predictor of Cu was log
      hsCRP. Serum Zn concentrations decreased with age. After adjustment for age,
      serum albumin, HDL cholesterol and red blood cell (RBC) were positively and serum
      insulin and log hsCRP were inversely associated with serum Zn. In stepwise
      multiple regression analysis (model 1), serum albumin and HDL cholesterol were
      associated with serum Zn. In analysis excluding albumin from model 1 (model 2),
      independent determinants were log hsCRP (inverse) and the total number of RBC. In
      analysis including serum creatinine in model 2, creatinine has emerged as a
      determinant in addition to log hsCRP and RBC number. In analysis including
      estimated glomerular filtration rate (eGFR) instead of creatinine and excluding
      age in model 2, eGFR has emerged as a determinant of serum Zn in addition to log
      hsCRP and RBC number. CONCLUSIONS: Systemic low-grade inflammation may contribute
      to elevated serum Cu and decreased serum Zn concentrations in the elderly, and
      may represent an important confounder of the relationship between the serum trace
      elements and mortality in this population.

PMID- 24901094
TI  - Serum osteocalcin is associated with dietary vitamin D, body weight and serum
      magnesium in postmenopausal women with and without significant coronary artery
      disease.
AB  - Osteoporosis and atherosclerosis often present atypically in postmenopausal
      women, making clinical recognition difficult. Prospective studies suggest
      independent associations between bone mass and vascular calcification through
      vitamin D deficiency as an established predictor of both conditions. We aimed to
      examine the relationship between serum osteocalcin and vitamin D status in
      postmenopausal women with and without angiographic evidence of coronary artery
      disease (CAD). One hundred and eighty postmenopausal women undergoing coronary
      angiography were selected sequentially from the Catheterization unit of King
      Abdulaziz University Hospital. Socio-demographic, anthropometric parameters and
      dietary habits were measured. Biochemical variables were estimated in blood
      samples. Half of the postmenopausal women did not have significant CAD, 24% had
      significant CAD in a single and/or double coronary vessels, 26% had significant
      CAD in three coronary vessels. Mean serum vitamin D concentrations showed that
      vitamin D deficiency was a common finding in the whole population. Vitamin D and
      calcium intakes were uniformly low in the study cohort. Serum osteocalcin was
      significantly correlated with dietary vitamin D in all subgroups (r=-0.172,
      p<0.05) and positively correlated among the patients (r=0.269, p=0.01). Serum
      magnesium, alkaline phosphatase, dietary vitamin D, and body weight were
      independent variables of serum osteocalcin level. In conclusion, elevated levels
      of serum C reactive protein and vitamin D were associated with low serum
      osteocalcin levels. Therefore, osteocalcin may be a potential cardiovascular risk
      marker. However, further studies are needed to clarify the pathophysiological
      processes underlying the relationship between serum osteocalcin level and
      atherosclerosis parameters. 

PMID- 24901095
TI  - Vitamin K nutritional status and undercarboxylated osteocalcin in postmenopausal
      osteoporotic women treated with bisphosphonates.
AB  - Serum undercarboxylated osteocalcin (ucOC) is an index of vitamin K nutritional
      status in treatment-naive postmenopausal osteoporotic women. The purpose of the
      present study was to reveal the association between vitamin K nutritional status
      and serum ucOC concentrations in postmenopausal osteoporotic women taking
      bisphosphonates. Eighty-six postmenopausal women with osteoporosis (age range: 47
      90 years) initiated bisphosphonate treatment. Vitamin K nutritional status was
      evaluated using a simple vitamin K-intake questionnaire and serum ucOC
      concentrations were measured after 6 months of treatment. The patients were
      divided into two groups according to the simple vitamin K-intake questionnaire
      score: a low vitamin K-intake (score <40) group (n=67) and a normal vitamin K
      intake (score >=40) group (n=19). There were no significant differences between
      the groups in baseline parameters including age, height, body weight, body mass
      index, serum alkaline phosphatase (ALP), urinary cross-linked N-terminal
      telopeptides of type I collagen (NTX), and changes in serum ALP and urinary NTX
      concentrations during the 6-month treatment period. However, the mean serum ucOC
      concentration after 6 months of treatment was significantly higher in the low
      vitamin K-intake group (2.79 ng/mL) than in the normal vitamin K-intake group
      (2.20 ng/mL). These results suggest that 78% of postmenopausal osteoporotic women
      treated with bisphosphonates may have vitamin K deficiency as indicated by low
      vitamin K-intake and high serum ucOC concentrations, despite having a similar
      reduction in bone turnover to women who have normal vitamin K-intake. 

PMID- 24901096
TI  - Women's nutrient intakes and food-related knowledge in rural Kandal province,
      Cambodia.
AB  - In Cambodia, both anaemia and vitamin A deficiency are serious health problems.
      Despite this, few comprehensive nutritional surveys have been completed to date.
      This study evaluates the adequacy of iron and vitamin A intakes, as well as
      women's nutritional knowledge in rural Kandal province. Twenty-four hour recalls,
      pile sort activities, socioeconomic surveys, focus groups, and market surveys
      were carried out with 67 women from 5 villages in rural Kandal Province. Ninety
      seven percent of women did not meet their daily-recommended intake of iron, while
      70% did not meet their daily-recommended intake of vitamin A. Although many women
      consume vitamin A-rich and iron rich-foods daily, they do not consume large
      enough quantities of these foods. Results suggest that both the cost of foods as
      well as the extent of health knowledge is linked to nutritional practice. Most
      animal-source iron and vitamin A-rich foods are considered expensive; however,
      small fish, and several plant-source vitamin A-rich foods are inexpensive and
      easy to access. Despite health education, food restrictions lead some healthy
      foods to be considered to be harmful to women. Ultimately, this study
      demonstrates the importance of developing comprehensive nutritional interventions
      in Cambodia. Health programming must provide women with not only suggestions to
      include low-cost nutrient-rich foods, but also advise them about the quantities
      that are likely to have an impact on nutritional status. Programs should take a
      community-based, inter-sectoral approach that simultaneously combines culturally
      informed health education with initiatives that combat poverty and increase
      access to nutrient rich foods. 

PMID- 24901097
TI  - Effect of feeding practices on dental caries among preschool children: a hospital
      based analytical cross sectional study.
AB  - Feeding practices during early childhood play an important aetiological role in
      early childhood caries (ECC). The role of feeding practices in causation of ECC
      is debated. The objective of this study was to assess the aetiological role of
      feeding practices on ECC. A descriptive cross sectional study was conducted at a
      paediatric unit in Sri Lanka. Two hundred and eighty-five children between 36 to
      60 months, admitted to the unit were randomly selected for the study. An
      interviewer administered questionnaire asked about socio-demographic
      characteristics and feeding practices. The mouths of children were examined for
      dental caries. Out of 285 children, 61% had exclusive breast feeding up to six
      months, 69% continued breast feeding beyond two years and 82% had overnight
      feeding after two years of age. One hundred and thirty-six children (47.7%) had
      dental caries with a mean deft score of 1.81. Overnight feeding with any type of
      milk beyond two years significantly increased dental caries incidence and
      severity. Children exclusively breast fed for six months or had breast feeding
      beyond two years had a higher prevalence of caries than children not exclusively
      breast fed or who were not breast feed beyond two years, but the difference was
      not significant. Overnight feeding with any type of milk beyond two years should
      be discouraged. 

PMID- 24901098
TI  - Assessment of iodine deficiency in school age children in Nainital District,
      Uttarakhand State.
AB  - Iodine deficiency disorder (IDD) is a major public health problem in Uttarakhand.
      The present study was conducted in district Nainital, Uttarakhand state with an
      objective to assess the prevalence of IDD in school age children. A total of 2269
      children in the age group of 6-12 years were included. Clinical examination of
      thyroid of all children was undertaken. "On the spot" urine samples were
      collected from 611 children. Salt samples were collected from the family kitchen
      for 642 children. The Total Goitre Rate (TGR) was 15.9%. The proportion of
      children with urinary iodine excretion levels <20, 20-49, 50-99, 100-199 and 200
      MUg/L and above, was nil, 11.8, 24.9, 38.3 and 25.0 percent, respectively. The
      median Urinary Iodine Excretion level was 125MUg/L. About 57.7% of the children
      were consuming salt with iodine content of 15 ppm and more. Findings of the
      present study indicates that the population is possibly in transition phase from
      iodine deficient as revealed by Total Goitre Rate of 15.9% to iodine sufficient
      as revealed by median urinary iodine excretion level of 125 MUg/L. There is a
      need to further strengthen the existing monitoring system for the quality of
      iodized salt in the district in order to achieve the elimination of IDD. 

PMID- 24901101
TI  - Type 2 diabetes among farmers and rural and urban referents: cumulative incidence
      over 20 years and risk factors in a prospective cohort study.
AB  - BACKGROUND: Few studies have examined the risk of type 2 diabetes in various
      occupational groups. Farmers in Sweden have a low risk of coronary heart disease,
      but less is known about diabetes. OBJECTIVE: To analyze the cumulative incidence
      and relative risk of type 2 diabetes among farmers and referents taking lifestyle
      factors and components of the metabolic syndrome into account. METHODS: In a
      longitudinal observational cohort study we followed 1,220 farmers, 1,130 rural
      non-farmer referents and 1,219 urban referents over 20 years. Outcomes were
      generated from national registers and from two surveys 12 years apart. Baseline
      data were assessed at the first survey conducted in 1990-91. RESULTS: Farmers had
      a significantly lower risk of all diabetes compared with urban and rural
      referents (p<0.05). A total of 91 farmers (8.4%) and 102 non-farming rural
      referents (11.5%) were identified with type 2 diabetes over the 20 year study
      period (OR=0.70; 95% CI 0.52-0.95). Fractional analyses of lifestyle factors and
      components of the metabolic syndrome showed that the low risk of type 2 diabetes
      among farmers was explained in terms of physical activity and meal quality.
      Farmers had significantly higher physical capacity (p<0.001) and scored higher in
      a meal quality index than rural referents (p<0.001). CONCLUSIONS: The prevalence
      of type 2 diabetes was significantly lower among farmers. The low relative risk
      was explained by high physical activity and better meal quality, indicating that
      farmers' lifestyles and their work environment are health-promoting.

PMID- 24901099
TI  - Nutritional status of breast-fed and non-exclusively breast-fed infants from
      birth to age 5 months in 8 Chinese cities.
AB  - This study aimed to assess the nutritional status of infants aged 0 to 5 months
      by different feeding approaches. A cross-sectional study on infant nutrition was
      performed in eight cities in China. A total of 622 infants from birth to 2 months
      of age and 456 infants from 3 months to 5 months of age were included in this
      study. Mix-fed infants received breast milk and complementary foods from birth to
      2 months of age. Approximately 38.2% of mix-fed infants received excessive
      vitamin A, and 15.6% of infants exceeded the tolerable upper intake levels (ULs)
      of zinc. For artificially fed infants who received only complementary foods,
      approximately 20% and 12.5% infants received inadequate dietary vitamin A and
      zinc intakes, respectively. The vitamin A and zinc intakes of half of the infants
      exceeded the ULs. Results showed that the usual intake distribution of the
      infants from 3 months to 5 months of age were similar to that of the infants from
      birth to 2 months of age. The common vitamin A and zinc intakes were also
      severely imbalanced. In addition, higher disease prevalence and lower Z scores of
      length-forage, weight-for-age, and weight-for-length were found in artificially
      fed infants and mix-fed infants compared with those in breast-fed infants. In
      conclusion, the usual nutrient intakes were adequate for the majority of Chinese
      infants, except for an important number of infants at risk for imbalance of
      vitamin A and zinc intakes. 

PMID- 24901100
TI  - The diamond level health promoting schools (DLHPS) program for reduced child
      obesity in Thailand: lessons learned from interviews and focus groups.
AB  - Overweight and obesity prevalence among children is increasing globally. Health
      promoting school policy has been initiated in Thailand to tackle this problem.
      The schools that best conduct obesity management programs are rated as diamond
      level health promoting schools (DLHPS). However, the methods used by these
      schools and their efficacies have not been well-documented. This qualitative
      study aims to analyze the processes and activities used by four DLHPSs in obesity
      management programs. In-depth interviews were used to obtain information from
      school directors, teachers, and cooks, whereas focus group discussions were used
      for students. School-based obesity management programs have resulted from health
      promoting school policy and the increasing prevalence of overweight students.
      Teamwork has been a key strategy in program implementation. Policy diffusion and
      division of labor have been effected by school directors. A monitoring process is
      put in place to ensure program delivery. The most evident success factor in the
      present study has been intersectoral cooperation. Challenges have included
      confusion about the criteria in obtaining the DLHPS status, parental involvement,
      and students' resistance to consume vegetables and other healthy foods. From the
      student focus groups discussions, three activities were most valued: class health
      and nutrition learning; provision of healthy foods and drinks, together with
      removal of soft drinks and seasoning from the cafeteria; and exercise for health.
      Intersectoral cooperation is the key success factor for the operationality of
      DLHPS, especially in making healthy foods available and physical activity the
      norm, at school and home. 

PMID- 24901102
TI  - Lifestyle of Chinese centenarians and their key beneficial factors in Chongqing,
      China.
AB  - OBJECTIVE: This study aims to describe the lifestyle of Chinese centenarians and
      to identify the beneficial factors that are correlated to their longevity.
      METHODS: A census-based survey was conducted among centenarians in Chongqing,
      Southwest China, to identify the lifestyle factors affecting their health. From
      screening identification cards, 878 centenarians (age range 100-117, mean 102)
      were identified and interviewed. RESULTS: The survey indicated that 64%
      centenarians were able to take care of themselves. The majority of centenarians
      were nonsmokers (92%) and non-drinkers (83%). No significant difference was
      observed between urban and rural distributions (Chi2=0.939, p=0.625). Moreover,
      43% centenarians maintained a regular diet, and only 33% had a sedentary
      lifestyle. CONCLUSIONS: A nutritious diet, adequate physical exercise, and a
      harmonious family environment may be the key lifestyle factors for their
      longevity of centenarians in Chongqing. These observations might be helpful in
      designing health promotion and welfare strategies for the elderly.

PMID- 24901103
TI  - Effectiveness of a food education program in improving appetite and nutritional
      status of elderly adults living at home.
AB  - OBJECTIVE: To evaluate a 3-week program comprising cooking demonstrations with
      free food samples in motivating elderly adults to cook more and improve their
      nutritional status. DESIGN: An experimental pre-post study. SETTING: Three
      districts in Hong Kong. PARTICIPANTS: Sixty aged 59-95 home-living adults.
      INTERVENTION: Group A (one 1-day food sample given free weekly) and Group B
      (three 1-day food samples given free weekly). MAIN OUTCOME MEASURE: Satisfaction
      questionnaires were conducted every week. Mini Nutritional Assessment (MNA)
      scores were assessed at baseline and 6 months after the program's completion.
      ANALYSIS: Nutritional status was assessed before and after intervention. Repeated
      analysis of variance measures of compliance, appetite, easiness of program at 3
      week time-points were calculated to differentiate a more frequent (Group B) and a
      less frequent (Group A) provision of food sample reinforced their cooking skills
      to a greater extent. RESULTS: The compliance rate of Group B was higher than that
      of Group A. More than 60% of the participants intended to continue cooking and a
      third of the participants expressed satisfaction with the program. The MNA scores
      had improved 6 months later (combined data from both groups). CONCLUSIONS:
      Nutrition education through cooking demonstrations and the community-based
      distribution of food ingredients can improve the nutrition status of the elderly
      population.

PMID- 24901104
TI  - Stockpiles and food availability in feeding facilities after the Great East Japan
      Earthquake.
AB  - Food stockpiles and methods of ensuring food availability after the Great East
      Japan Earthquake of March 11, 2011 have been studied. Questionnaires were sent to
      1911 registered dietitians and general dietitians who were members of the Japan
      Dietetic Association in August 2012. Four hundred thirty-five dietitians (22.8%)
      completed the questionnaire about work involved in feeding facilities, types and
      administration of meals, and food stockpiles. Methods of ensuring food
      availability, preparation, and accommodating food for special dietary uses were
      recorded for the three-day period immediately following the earthquake, and the
      period from 4 days to one month after the earthquake. Three days after the
      earthquake, differences in administration of meals at feeding facilities
      providing three meals daily, food stockpiles, organization, contactable
      facilities, and how to contact them for food items were assessed. Sixty-nine
      percent of all feeding facilities in this study had stockpiles of food before the
      Great East Japan Earthquake. Administration of meals in feeding facilities and
      the possibility of contact with cooperative feeding facilities were found to
      correlate positively with ensuring the availability of food groups. Food scores
      were higher in facilities providing three meals daily by direct administration of
      meals and with accessible public administrators, cooperative facilities and
      suppliers, and facilities that were contactable by landline telephone, mobile
      phone, fax or email. The necessity for natural disaster-readiness through
      continuous stockpiling food at feeding facilities is confirmed. Each prospective
      feeding facility must be required to plan its stockpiles, their turnover and
      replaceability to maximise food security in the face of disaster. 

PMID- 24901105
TI  - MicroRNA-125a-3p expression in abdominal adipose tissues is associated with
      insulin signalling gene expressions in morbid obesity: observations in Taiwanese.
AB  - BACKGROUND: Micro (mi) RNAs have been found to play an important role in the
      regulation of adipogenesis and insulin sensitivity. However, associations between
      miRNA and insulin signalling-related gene expressions in abdominal adipose
      tissues in obese subjects remain unclear. METHODS: We used a microarray platform
      to screen miRNA expressions in abdominal adipose tissues between genders in
      severely obese subjects and found that the top-ranking miRNA in abdominal omental
      adipose tissues was miRNA-125a-3p. MicroR-125a-3p and insulin signalling-related
      gene expressions in abdominal omental adipose tissues of all subjects (11 men and
      10 women) were subsequently quantified by a real-time PCR. Also, associations of
      miR-125a-3p with insulin signalling-related gene expression and biochemical
      markers in obese subjects were analyzed by a linear regression analysis. RESULTS:
      miR-125a-3p expressed by abdominal omental adipose tissues was much higher in
      obese men than women. No gender difference was observed in abdominal subcutaneous
      adipose tissues. Concomitant with high miR-125a-3p, c-Jun N-terminal kinase gene
      expression was also higher, whereas insulin receptor was lower in men than women.
      There were negative associations of miR-125a-3p with the insulin receptor and
      phosphatidylinositol 3-kinase expressions. Fasting plasma glucose and cholesterol
      levels were positively associated with miR- 125a-3p expression. These
      associations were obvious in obese men but not women. CONCLUSION: Our results
      support the involvement of miR-125a-3p in regulating the insulin signalling
      pathway and imply that increased miR- 125a-3p expression in omental adipose
      tissues may be a characteristic feature of insulin resistance in obese men.

PMID- 24901106
TI  - Accessing the third dimension in localization-based super-resolution microscopy.
AB  - Only a few years after its inception, localization-based super-resolution
      microscopy has become widely employed in biological studies. Yet, it is primarily
      used in two-dimensional imaging and accessing the organization of cellular
      structures at the nanoscale in three dimensions (3D) still poses important
      challenges. Here, we review optical and computational techniques that enable the
      3D localization of individual emitters and the reconstruction of 3D super
      resolution images. These techniques are grouped into three main categories: PSF
      engineering, multiple plane imaging and interferometric approaches. We provide an
      overview of their technical implementation as well as commentary on their
      applicability. Finally, we discuss future trends in 3D localization-based super
      resolution microscopy. 

PMID- 24901107
TI  - Two-way effects of surfactants on Pickering emulsions stabilized by the self
      assembled microcrystals of alpha-cyclodextrin and oil.
AB  - The influence of surfactants on the stability of cyclodextrin (CD) Pickering
      emulsions is not well understood. In this study, we report two-way effects of
      Tween 80 and soybean lecithin (PL) on the long term stability of Pickering
      emulsions stabilized by the self-assembled microcrystals of alpha-CD and medium
      chain triglycerides (MCT). The CD emulsions in the absence and presence of Tween
      80 or PL at different concentrations were prepared and characterized by the
      droplet size, viscosity, contact angle, interfacial tension and residual emulsion
      values. After adding Tween 80 and PL, similar effects on the size distribution
      and contact angle were observed. However, changes of viscosity and interfacial
      tension were significantly different and two-way effects on the stability were
      found: (i) synergistic enhancement by Tween 80; (ii) inhibition at low and
      enhancement at high concentrations by PL. The stability enhancement of Tween 80
      was due to the interfacial tension decrease caused by the interaction of Tween 80
      with CD at the o/w interface at lower concentrations, and significant viscosity
      increase caused by the Tween 80-CD assembly in the continuous phase. For PL at
      low concentrations, the replacement of alpha-CD/MCT by alpha-CD/PL particles at
      the o/w interface was observed, leading to inhibitory effects. High
      concentrations of PL resulted in an extremely low interfacial tension and stable
      emulsion. In conclusion, the extensive inclusion of surfactants by CD leads to
      their unique effects on the stability of CD emulsions, for which the changes of
      viscosity and interfacial tension caused by host-guest interactions play
      important roles. 

PMID- 24901108
TI  - Temporal trends in incidence and outcomes of peripartum cardiomyopathy in the
      United States: a nationwide population-based study.
AB  - BACKGROUND: The reported incidence of peripartum cardiomyopathy (PPCM) in the
      United States varies widely. Furthermore, limited information is available on the
      temporal trends in incidence and outcomes of PPCM. METHODS AND RESULTS: We
      queried the 2004-2011 Nationwide Inpatient Sample databases to identify all women
      aged 15 to 54 years with the diagnosis of PPCM. Temporal trends in incidence (per
      10 000 live births), maternal major adverse events (MAE; defined as in-hospital
      mortality, cardiac arrest, heart transplant, mechanical circulatory support,
      acute pulmonary edema, thromboembolism, or implantable cardioverter
      defibrillator/permanent pacemaker implantation), cardiogenic shock, and mean
      length of stay were analyzed. From 2004 to 2011, we identified 34 219 women aged
      15 to 54 years with PPCM. The overall PPCM rate was 10.3 per 10 000 (or 1 in 968)
      live births. PPCM incidence increased from 8.5 to 11.8 per 10 000 live births
      (Ptrend<0.001) over the past 8 years. MAE occurred in 13.5% of patients. There
      was no temporal change in MAE rate, except a small increase in in-hospital
      mortality and mechanical circulatory support (Ptrend<0.05). Cardiogenic shock
      increased from 1.0% in 2004 to 4.0% in 2011 (Ptrend<0.001). Mean length of stay
      decreased during the study period. CONCLUSION: From 2004 to 2011, the incidence
      of PPCM has increased in the United States. Maternal MAE rates overall have
      remained unchanged while cardiogenic shock, utilization of mechanical circulatory
      support, and in-hospital mortality have increased during the study period.
      Further study of the mechanisms underlying these adverse trends in the incidence
      and outcomes of PPCM are warranted.

PMID- 24901110
TI  - [Tonsillectomy use in children- preemptive triple therapy can relieve pain].

PMID- 24901109
TI  - Psychometric evaluation of the Care Transition Measure in TRACE-CORE: do we need
      a better measure?
AB  - BACKGROUND: The quality of transitional care is associated with important health
      outcomes such as rehospitalization and costs. The widely used Care Transitions
      Measure (CTM-15) was developed with a classic test theory approach; its short
      version (CTM-3) was included in the CAHPS Hospital Survey. We conducted a
      psychometric evaluation of both measures and explored whether item response
      theory (IRT) could produce a more precise measure. METHODS AND RESULTS: As part
      of the Transitions, Risks, and Actions in Coronary Events Center for Outcomes
      Research and Education, 1545 participants were interviewed during an acute
      coronary syndrome hospitalization, providing information on general health status
      (Short Form-36), CTM-15, health utilization, and care process questions at 1
      month postdischarge. We used classic and IRT analyses and compared the
      measurement precision of CTM-15-, CTM-3-, and CTM-IRT-based score using relative
      validity. Participants were 79% non-Hispanic white and 67% male, with an average
      age of 62 years. The CTM-15 had good internal consistency (Cronbach's alpha=0.95)
      but demonstrated acquiescence bias (8.7% participants responded "Strongly agree"
      and 19% responded "Agree" to all items) and limited score variability. These
      problems were more pronounced for the CTM-3. The CTM-15 differentiated between
      patient groups defined by self-reported health status, health care utilization,
      and care transition process indicators. Differences between groups were small (2
      to 3 points). There was no gain in measurement precision from IRT scoring. The
      CTM-3 was not significantly lower for patients reporting rehospitalization or
      emergency department visits. CONCLUSION: We identified psychometric challenges of
      the CTM, which may limit its value in research and practice. These results are in
      line with emerging evidence of gaps in the validity of the measure.

PMID- 24901111
TI  - Executives discuss employee productivity and performance: is health a means to
      that end?

PMID- 24901112
TI  - Do health-related behaviors ignite performance?

PMID- 24901113
TI  - Expert comments on "The Hopeful Case of Kanban International".

PMID- 24901114
TI  - Commentary: The high performance workplace: can wellness play a role?

PMID- 24901115
TI  - [Therapy for tongue cancer - reconstruction with buccinator flap].

PMID- 24901116
TI  - Editorial.

PMID- 24901117
TI  - [Neonatal primary care -- "atypical intubation" in tracheal agenesie].

PMID- 24901118
TI  - [Teaching Obstetrics -- the phantom of the pocket].

PMID- 24901119
TI  - Physicians as partners in mission.

PMID- 24901121
TI  - [Diphyllobothrium latum].

PMID- 24901122
TI  - The correlation between serum VEGF levels and known prognostic risk factors in
      colorectal carcinoma.
AB  - BACKGROUND/AIMS: In the present study, we analyzed serum vascular endothelial
      growth factor (VEGF) levels and its correlation with the other
      clinicopathological characteristics of patients with colorectal carcinoma (CRC).
      METHODOLOGY: Seventy-one patients (F/M, 29/42; Mean age +/- SD, 53.3 +/- 13.1
      years) were included. The results of serum VEGF were analysed with respect to
      stage, gender, age, CEA, metastases and topographical tumour localization.
      RESULTS: Patients with stage 3-4 disease had significantly higher values of VEGF
      (253.41 pg/mL +/- 302.24) than patients with stage 1-2 (49.99 pg/L +/- 100.30) (P
      < 0.003). Patients with the primary tumour localized in the colon had no
      significantly higher levels of serum VEGF than patients with the primary tumour
      localized in the rectum (225.97 +/- 324.88 pg/mL vs. 153.76 +/- 205.66 pg/ mL,
      respectively, P = 0.269). The VEGF expression significantly correlated with serum
      CEA level (P < 0.01) and clinical stages of colorectal cancer (P < 0.01). The
      VEGF expression was not correlated with patients' age (P = 0.955) and gender (P =
      0.740). CONCLUSIONS: The VEGF expression significantly correlated with advanced
      stage, and metastases but not age, gender, and tumour localization. VEGF may play
      an important role in the invasion and metastasis of CRC. Therefore, VEGF could be
      applied as prognostic markers in CRC.

PMID- 24901123
TI  - Research on the epigenetic modification of pancreatic cancer vaccine.
AB  - Pancreatic cancer is characterized as a type of gastrointestinal tumor with a
      poor prognosis and high degree of malignancy. CIITA gene was found highly
      methylated in pancreatic carcinoma cell line PANC-1 and responsible for the low
      expression of MHC-II that may lead to immune evasion. Here, we tried to prepare
      pancreatic cancer vaccine with PANC-1 cells via epigenetic modification to
      enhance the MHC-II expression. Then the vaccine was injected into C57BL/6J mice
      and the effect was examined. Our study found that the vaccine could promote the
      proliferation of antigen-specific T cells, enhance the killing activity of
      cytotoxic lymphocytes (CTL), promote Th1-type cells mediated secretion of
      cytokines IFN-gamma and IL-2 while inhibiting Th2-type cells mediated secretion
      of IL-4, and inhibit the secretion of TGF-beta. Generally, the epigenetically
      modified vaccine could enhance the body's anti-tumor immune response, providing
      feasibility research on cancer vaccine for therapy of pancreatic cancer.

PMID- 24901124
TI  - GPC3 DNA vaccine elicits potent cellular antitumor immunity against HCC in mice.
AB  - BACKGROUND/AIMS: DNA-based tumor vaccine immunotherapy which elicits exclusively
      cellular immune response against cancer cells in an antigen-specific fashion has
      been documented to be an effective treatment for cancers in the past decade.
      Glypican 3 (GPC3) is especially overexpressed in hepatocellular carcinoma (HCC),
      but not in benign liver lesions and normal adult tissues, which makes it an ideal
      tumor antigen designed for HCC immunotherapy. METHODOLOGY: We constructed a GPC3
      cDNA vaccine by using a recombinant plasmid encoding murine GPC3 cDNA for
      treatment of HCC in a C57BL/6 mouse model. The specificity and effectiveness of
      anti-tumor immunity were assessed in vitro and in vivo studies. RESULTS: In vitro
      studies showed that GPC3 DNA vaccine induced potent specific cytotoxic T
      lymphoctyes (CTLs) immune response against C57BL/6 homogenous HCC cell line Hepa
      1-6 (GPC3+). However, there was no detectable immune response against GPC3
      negative SP 2/0 cells and Sk-Hep-1 cells. In vivo study indicated that GPC3 DNA
      vaccine could significantly suppress homogenous tumor growth and prolong survival
      time of tumor bearing mice. CONCLUSIONS: This study demonstrated the first time
      that the GPC3 DNA vaccine could elicit specific and effective cellular antitumor
      immunity against GPC3 HCC. This may provide an alternative option for
      immunotherapy of HCC.

PMID- 24901125
TI  - Laparoscopic splenectomy for adult lymphangiomas of the spleen: case series and
      review of literature.
AB  - BACKGROUND/AIMS: Spleen lymphangiomas are rare congenital malformations of the
      lymphatics. There is a paucity of data in the literature on the evaluation and
      laparoscopic treatment for adult spleen lymphangiomas. The aim of this study is
      to further elucidate the feature of this tumor and laparoscopic management of
      spleen lymphangiomas. METHODOLOGY: From September 2006 to February 2011, data was
      collected retrospectively for all patients who underwent laparoscopic splenectomy
      in our institution with a diagnosis of spleen lymphangiomas. The perioperative
      details were recorded as well as follow-up. RESULTS: Seven adult patients
      underwent successfully LS for spleen lymphangiomas. Mean age was 47.9 years and
      five patients (71.4%) were women. Patients' symptoms included abdominal pain
      (28.6%), palpable abdominal mass with nausea (14.3%). Four patients (57.1%) were
      asymptomatic at diagnosis. The preoperative diagnosis depended on
      ultrasonography, computed tomography and final needle aspiration. No patient had
      multiple splenic lesions before. Mean operative time was 112 min. Mean estimated
      blood loss was 78.6 ml. Pathological examinations confirmed the preoperative
      diagnosis. No preoperative and postoperative complications have occurred. There
      were no recurrences at a median follow-up of 31 months. CONCLUSIONS: Laparoscopic
      splenectomy is a preferred treatment for patients with suspected cystic
      lymphangioma. It should be preferred to total splenectomy.

PMID- 24901126
TI  - An association of elevated levels of alkaline phosphatase and gamma-glutamyl
      transpeptidase with acute cholangitis.
AB  - BACKGROUND/AIMS: The early diagnosis of acute cholangitis (AC) is critical for
      appropriate treatment. METHODOLOGY: Patient records from April 2008 to December
      2012 were retrospectively analyzed. Data on white blood cell count and levels of
      C-reactive protein, total-bilirubin, alkaline phosphatase (ALP), aspartate
      aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase
      (gamma-GTP) were collected from AC patients on the day they underwent endoscopic
      retrograde cholangiopancreatography (ERCP) for diagnosis and treatment. Data were
      collected 3 months before ERCP to analyze the rate of change of these variables.
      Receiver operating characteristics curve analysis was performed. RESULTS: We
      enrolled 63 patients with AC and 65 patients with non-AC. The threshold values of
      ALP and gamma-GTP were 1.09 and 1.30, respectively. CONCLUSIONS: 450 (IU/L) and
      100 (IU/L), respectively, were thresholds of ALP and gamma-GTP on the day of
      ERCP. 1.09 and 1.30, respectively, were thresholds of ALP and gamma-GTP rates of
      change for the diagnosis of AC.

PMID- 24901127
TI  - The use of ERCP during pregnancy: is it safe and effective?
AB  - Cholangitis and pancreatitis are the most gruesome complications that can be
      potentially fatal for the mother and fetus. The management of bile stone disease
      complicated with duct stones during pregnancy is challenging. Conservative
      treatment instead of surgery has always been advocated due to the increased risk
      for fetal compromise. Minimally invasive therapy with ERCP has been suggested as
      an effective therapeutic option for the management of pancreaticobiliary diseases
      during pregnancy. The main topics of discussion are the risks stemming from the
      endoscopic procedure itself, drugs used for sedation and the adverse effects of
      radiation exposure on the fetus. In this manuscript, we want to present the
      efficiency and feasibility of the ERCP for the management of hepatobiliary and
      pancreatic diseases in pregnancy.

PMID- 24901128
TI  - Optimal selection of methods for mini-invasive treatment of extrahepatic bile
      duct stones.
AB  - BACKGROUND/AIMS: This study aims to identify the optimal mini-invasive treatment
      for extrahepatic bile duct stones. METHODOLOGY: One hundred and seventy eight
      patients with EHBD stones were randomized into 4 groups: laparoscopic
      cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) plus T
      tube drainage (group LT), LC and LCBDE with endonasobiliary drainage (ENBD) tube
      (group LE), and endoscopic sphincterotomy with ENBD followed by LC (group EE) and
      T-tube drainage of open CBDE (group OT). Demographic data, perioperative
      findings, postoperative outcomes, hospital expense, gastrointestinal quality of
      life index (GIQLI) scores and cost per quality-adjusted life year (QALY) were
      analyzed. RESULTS: The operating time was longest in group EE. There was less
      bleeding in group OT and EE. Group LE and EE had shorter hospital stay and
      recovery time of intestinal motility. The postoperative white blood cell count
      and serum C-reaction protein level were higher in group LT and OT.
      Postoperatively, the mean GIQLI scores in group LE and EE were higher. Mean cost
      were highest in group EE. Patients in group LE had lowest cost per QALY.
      CONCLUSIONS: The modified laparoscopic procedure, LC combined with LCBDE followed
      by a primary closure over the ENBD tubes, appears to be the best option for
      patients with EHBD stones.

PMID- 24901129
TI  - Is T-stage the only significant factor determining the extent of surgery for
      gallbladder cancer?
AB  - BACKGROUND/AIMS: T-stage is currently the only factor determining the extent of
      surgery of gallbladder cancer (GBCA). We hypothesized that perineural invasion
      could be another predictive factor determining the extent of surgery because it
      is very powerful prognostic factor for GBCA. METHODOLOGY: A retrospective
      analysis was carried out of patients who underwent operation for gallbladder
      cancer between February 1991 and November 2011. The data were retrospectively
      analyzed and reviewed and the microscopic findings were checked by a pathologist.
      RESULT: Simple and extended cholecystectomy was performed in 82 patients during
      the study period. In univariate analysis, CA 19-9 level, gross type, depth of
      invasion, lymph node metastasis, distant metastasis, perineural invasion,
      lymphatic invasion and vascular invasion were associated with survival (P <
      0.05). In multivariate analysis, perineural invasion and vascular invasion had an
      impact on survival (P < 0.05). CONCLUSIONS: T and N stage are powerful prognostic
      factor for GBCA, but perineural invasion and vascular invasion are also
      significant prognostic factors. To improve survival radical resection should be
      considered in early GBCA with perineural and vascular invasion.

PMID- 24901130
TI  - Effect evaluation of vascular resection for patients with hilar
      cholangiocarcinoma: original data and meta-analysis.
AB  - BACKGROUND/AIMS: To evaluate the effect of vascular resection (VR) in surgical
      management of hilar cholangiocarcinoma (HCCA), this report did a clinical
      analysis and conducted a systematic review, combined other studies, based on meta
      analysis. METHODOLOGY: Two hundred and thirty eight HCCA patients underwent
      hepatectomy in the Eastern Hepatobiliary Surgery Hospital. Binary logistic
      regression analysis was performed to investigate the potentially complications
      associated factors. Kaplan-Meier test was employed to compare the long-term
      survival of patients in four groups (RO + PVR-free, RO + PVR, R1 and R2). Meta
      analysis was performed with RevMan 4.3.2 software. RESULTS: The results suggested
      that hepatectomy and HAR were important negative factors from complications (P <
      0.01). Compared with patients in other groups, survival of patients in RO + PVR
      group was worse than RO + PVR-free group, better than R2 group and similar to R1
      group with P = 0.001, 0.047 and 0.606 respectively. The results of meta-analysis
      suggested patients who underwent VR had higher complications rate and mortality
      rate than patients who did not. Moreover, patients with vascular resection had
      lower long-term survival rate. CONCLUSIONS: VR used to be considered effective to
      the patients with vascular invasion. However our study suggest that the surgical
      decision of undergoing VR should be made cautiously, since VR could diminish the
      survival time in some cases.

PMID- 24901132
TI  - Comparative study on laparoscopic sleeve gastrectomy and laparoscopic gastric
      bypass for treatment of morbid obesity patients.
AB  - BACKGROUND/AIMS: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most
      widely used bariatric procedures for the treatment of morbid obesity.
      Laparoscopic sleeve gastrectomy (LSG) is a relatively innovative procedure which
      has been increasingly accepted as a sole bariatric procedure in the Asian-Pacific
      region. This study aims to compare mid-term outcomes in morbid obesity patients
      undergoing LRYGB and LSG. METHODOLOGY: Between January 2008 and May 2011, 94
      morbid obesity patients were assigned by patient choice after informed consent to
      either a LSG (n = 56) or LRYGB (n = 38) group. We compared operation time, amount
      of bleeding, hospital length-of-stay, complications, improvement of diabetic
      patients, BMI, and excess weight loss (EWL) at 6-30 months post-operation.
      RESULTS: There was no death in either group. The operating time, hospital length
      of-stay, and complications were significantly shorter in the LSG group (P <
      0.05). There was no significant difference in the overall improvement of diabetes
      mellitus (P > 0.05). LRYGB had better effectiveness than LSG in BMI decrease and
      EWL in the first year (P < 0.05), but there was no significant difference after 1
      year (P > 0.05). CONCLUSIONS: The two procedures are safe and effective, but the
      LRYGB procedure incurs a high number of complications and long hospital stay. LSG
      is a promising bariatric procedure and the results of LSG as a single procedure
      are equally effective to LRYGB at 2 years follow-up on weight reduction.
      Furthermore, the LSG group has a more stable EWL in the early stage. However,
      studies with large number of patients and longer follow-up are necessary to make
      a definitive conclusions.

PMID- 24901131
TI  - Adjuvant chemotherapy using gemcitabine for resected distal bile duct and
      ampullary cancers.
AB  - BACKGROUND/AIMS: This retrospective study aimed to evaluate adjuvant chemotherapy
      using gemcitabine for resected distal bile duct and ampullary cancers.
      METHODOLOGY: Thirty-seven patients who had curative surgery for distal bile duct
      and ampullary cancers were classified into two groups: A, 19, surgery alone, and
      B, 18, surgery plus gemcitabine adjuvant chemotherapy between 2004 and 2010.
      Outcomes, including backgrounds, overall survival (OS), disease free survival
      (DFS), and adverse events are reported. RESULTS: There were no differences in
      characteristics between patients of groups A and B for age, gender, location of
      tumor, UICC stage, UICC pT factor, UICC pN factor, curability, and operative
      procedures. For all stages, except stage II, there was no difference between
      groups A and B for OS and DFS. For stage II however, groups A and B showed
      significant differences in median survival times for OS and DFS. Grade 3 or 4
      adverse events included 5.6% with leucopenia. CONCLUSIONS: Adjuvant chemotherapy
      using gemcitabine showed the potential of contributing to prolonged OS and DFS in
      stage II resected distal bile duct and ampullary cancers. However, a large cohort
      will be needed to confirm the overall efficacy in all stages of resected BTC's.

PMID- 24901133
TI  - Efficacy and safety of sitagliptin for the treatment of nonalcoholic fatty liver
      disease with type 2 diabetes mellitus.
AB  - BACKGROUND/AIMS: Dipeptidyl peptidase-4 inhibitor is useful for the treatment of
      type 2 diabetes mellitus (DM). However, effects on liver function and glucose
      metabolism in nonalcoholic fatty liver disease (NAFLD) have not been established.
      The objective of this study was to evaluate the efficacy and safety of
      sitagliptin in NAFLD patients with type 2 DM. METHODOLOGY: Forty-four patients
      with biopsy-proven NAFLD with type 2 DM were evaluated. Patients were
      administered sitagliptin (50 mg/day) for 12 months. RESULTS: Hemoglobin A1c
      (HbA1c) decreased by 0.7% after treatment (P < 0.001). While HbA1c levels
      decreased by 0.4% in the low HbA1c (< 7.5%) group, those decreased by 1.2% in the
      high HbAlc (> or = 7.5%) group. Liver transaminases did not change significantly
      during the treatment. Improvement of HbA1c (deltaHbA1c) and that of aspartate
      aminotransferase (deltaAST), alanine aminotransferase (deltaALT) was positively
      correlated (r = 0.425, and 0.455, respectively), especially in the high HbA1c (>
      or = 7.5%) group before treatment (r = 0.568, and 0.501, respectively).
      CONCLUSIONS: Sitagliptin for the treatment of NAFLD with type2 DM was safe and
      showed similar antidiabetic effects as reported for type 2 DM, suggesting that
      tight glycemic control would contribute to the improvement of NAFLD based from
      the findings of correlation between the changes of HbA1c and transaminases.

PMID- 24901134
TI  - Unchanged expression of whole neurons in the myenteric plexus in the neorectum
      after anterior resection.
AB  - BACKGROUND/AIMS: We aimed to study the distribution of neurons in the myenteric
      plexus of the neorectum after anterior resection and determine changes in the
      number of whole neurons. METHODOLOGY: From January 2002 to December 2008, 20
      patients with local recurrence or new neoplasms in the neorectum after anterior
      resection for rectal cancer were enrolled in the neorectum group and another 20
      patients with sigmoid colon cancer allocated by age and gender were enrolled in
      the control group. Formalin-fixed, paraffin embedded tissue sections were
      collected and studied using anti-HuC/HuD. The number of whole neurons in the
      myenteric plexus were counted postoperatively. RESULTS: The mean number of whole
      neurons in the myenteric plexus was 8.22 +/- 2.70/mm in neorectum group vs. 8.16
      +/- 2.67/mm in control group (P = 0.944), without significant difference.
      CONCLUSIONS: After anterior resection, whole neurons in the myenteric plexus in
      the neorectum did not change. The denervation has no effect on the change of the
      number of whole neurons in the myenteric plexus in the neorectum.

PMID- 24901135
TI  - Transanal endoscopic proctectomy: a case in swine.
AB  - Laparoscopic total mesorectal excision has been proven safe and effective in the
      radical minimally invasive surgical treatment of rectal cancer. However,
      technical difficulties may impose challenges to completion of the procedure
      leading to an eventually high conversion rate. Transanal endoscopic proctectomy
      using available minimally invasive rectal surgery platforms represents an
      ingenious approach to surgery in the extraperitoneal rectum. It was aimed at
      evaluating the feasibility of this natural orifice translumenal endoscopic
      surgery rectosigmoid resection in the swine. Full-thickness circumferential
      rectal dissection was performed and extended proximally. After distal colon and
      rectal mobilization, the specimen was exteriorized and transected, and the
      proximal colon was stapled to the distal rectum. In this feasibility non-survival
      study, operation time was 3 h 10 min, the specimen length was 12 cm and it was
      intact regarding rectal wall and attached mesorectum. Injuries to adjacent organs
      were not observed. Transanal endoscopic proctectomy proved feasible in one swine
      model and might represent an option to the difficult laparoscopic total
      mesorectal excision.

PMID- 24901136
TI  - The outcomes and prognostic factors of surgical treatment for ischemic colitis:
      what can we do for a better outcome?
AB  - BACKGROUND/AIMS: Surgical treatment is mandatory for severe ischemic colitis, but
      morbidity and mortality are high. We evaluated the outcomes and prognostic
      factors of surgical treatment for ischemic colitis. METHODOLOGY: Forty-nine
      consecutive patients (M:F, 26:23, median, 63 years), who underwent surgery for
      ischemic colitis by single surgeon, had been recruited prospectively and
      retrospectively analyzed. RESULTS: The causes of ischemia were vascular
      occlusions in 35 (71.4%). Thirty-seven (75.5%) patients had coexisting chronic
      medical problems. Emergency operation was performed in 40 (81.6%). Ischemic
      regions were right colon in 20 (40.8%), left colon in 19 (38.8%), and whole colon
      in 9 (18.4%). Resection with stoma formation was performed in 29 (59.2%) and
      primary anastomosis in 19 (38.8%). Postoperative morbidity occurred in 42 (85.7%)
      and mortality in 22 (44.9%). Univariate analysis showed that abdominal pain with
      peritoneal irritation signs, systemic inflammatory response, severe systemic
      hypotension, cardiovascular disease, vasoactive drug, emergency operation, and
      stoma formation were unfavorably associated with morbidity and/or mortality.
      Preoperative severe systemic hypotension was the only significant risk factor of
      mortality in multivariate analysis. CONCLUSIONS: Morbidity and mortality remained
      high in surgery for ischemic colitis. As preoperative systemic hypotension was
      the most important, early surgical treatment before the disease being
      deteriorated is mandatory.

PMID- 24901137
TI  - Decreased cellular levels of palmitic amide are linked to 5-fluorouracil
      resistance in human colon cancer cells.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate whether profiling
      metabolic compounds in human colon cancer cells with induced 5-florouracil
      resistance enables identification of predictive biomarkers for 5-florouracil
      resistance. METHODOLOGY: 5-florouracil resistant and parental cells were
      extracted using methanol/chloroform solution, and analyzed by MALDI-TOF.
      Principal components analysis and discriminant analysis was performed to select
      low-mass ions with strong discriminating power between 5-florouracil resistant
      and parental cells. The correlation between the intensities of low-mass ions and
      intrinsic 5-florouracil resistance in 11 colon cancer cells was analyzed using
      the Spearman rank coefficient. RESULTS: Eleven low-mass ions had strong discrimi
      nating power between 5-florouracil-resistant and parental cells. Of these, the
      intensity of a low-mass ion with 256.29 m/z was negatively correlated with
      intrinsic 5-florouracil resistance in 11 colon cancer cells (r = -0.6545, P =
      0.0338). By searching the H+ adduct with 0.05 m/z tolerance in the Human
      Metabolome Database, a low-mass ion of 256.29 m/z was identified as palmitic
      amide. Interestingly, extracellular treatment with palmitic amide reduced 5
      florouracil resistance and invasiveness in 5-florouracil-resistant cells.
      CONCLUSIONS: Palmitic amide showed potential not only as a predictor of 5
      florouracil resistance, but also for reduction of 5-florouracil resistance in
      colon cancer cells.

PMID- 24901138
TI  - Management of peritoneal effusion by sealing with a self-assembling nanofiber
      polypeptide following pelvic surgery.
AB  - BACKGROUND/AIMS: PuraMatrix is a synthetic material consisting of 16-amino acid
      peptides that self-assemble into nanofibers, previously used as a scaffold for
      functional cell cultures. We conducted a clinical study to determine the safety
      and sealing properties of PuraMatrix in post-operative lymphorrhea following
      pelvic surgery in humans. METHODOLOGY: A total of 20 patients who underwent
      rectal cancer resection were analyzed. The study group (n = 10) consisted of
      patients who received PuraMatrix, matched with a control group (n = 10) of
      patients operated on conventionally. RESULTS: During the 2 to 3 month follow-up
      period, there were no abnormal findings or adverse events in any the patients who
      received PuraMatrix. We found that the patients who received PuraMatrix had
      significantly reduced post-operative drainage volumes compared with the patients
      in the control group. CONCLUSIONS: PuraMatrix is a safe and effective bio
      compatible sealing material for the management of post-operative peritoneal
      effusion following pelvic surgery.

PMID- 24901139
TI  - p16 Methylation is frequently detected in the serum of metastatic colorectal
      cancer patients.
AB  - For the purpose of detection of colorectal cancers, we tried to detect p16
      methylation in the serum of colorectal cancer patients using quantitative
      methylation-specific polymerase chain reaction (qMSP). Out of 211 serum samples
      derived from colorectal cancer patients, 14 (7%) exhibited p16 methylation in
      their serum DNA by qMSP. After completion of qMSP analysis in all specimens,
      clinicopathological data were correlated with the molecular analysis.
      Interestingly, a significant difference was observed in the presence of distant
      metastasis (P = 0.0420). Moreover, a trend was shown toward preferentially
      developing lymph node metastasis (P = 0.0547), thus suggesting that p16
      methylation in serum could be detected more frequently in metastatic colorectal
      cancer patients. High sensitivity of qMSP makes it possible to detect smaller
      amounts of tumor DNA in the serum. In principle, the methylation status of a
      primary tumor is not required in advance to detect circulating tumor DNA,
      suggesting that qMSP can be used as a screening method for cancer.

PMID- 24901140
TI  - Serial changes of serum cytokines in Crohn's disease following treatment with
      adalimumab.
AB  - BACKGROUND/AIMS: We examined serum cytokine levels in Crohn's disease (CD)
      patients before and after Adalimumab (ADA) treatment. METHODOLOGY: A total of 24
      patients with CD were enrolled (4 colonic type, 6 ileal type, 14 ileo-colonic
      type). Patients were divided into two groups according to disease duration.
      Patients were given ADA (160 mg at week 0 and 80 mg at week 2), followed by
      maintenance therapy (40 mg every other week). Serum levels of 17 cytokines were
      simultaneously determined using a Bio-Plex suspension array system before, 4 and
      8 weeks after ADA treatment. Serum CRP levels were also measured before, 4 and 8
      weeks after treatment. RESULTS: IL-6 and MCP-1 levels were significantly
      decreased in all CD patients and in the ileo-colonic type 8 weeks after ADA
      treatment compared to before treatment (P <0.05). MCP-1 levels were significantly
      decreased 8 weeks after treatment compared to pre-treatment samples if disease
      onset occurred longer than 8 years. A significant correlation was noted between
      CRP and IL-6 levels. CONCLUSIONS: The reduction of IL-6 and MCP-1 would be an
      important role for the improvement of inflammation after ADA treatment in CD
      which might be associated with disease types and disease duration,

PMID- 24901141
TI  - Liquid tissue adhesive, subcuticular suture and subcutaneous closed suction drain
      for wound closure as measures for wound infection in a colorectal cancer surgery
      with stoma creation.
AB  - BACKGROUND/AIMS: Stoma creation is one of the risk factors for the incisional
      surgical site infection (SSI) which can develop the patient's pain in a
      colorectal surgery. METHODOLOGY: We performed the subcuticular suture with
      subcutaneous negative pressure drainage and sealing with liquid tissue adhesive
      for the prevention of wound infection at the stoma creation. RESULTS: A total of
      72 patients between January 2006 and December 2012 were retrospectively analyzed.
      Up to December 2008, the wound closure was performed by the percutaneous
      transdermal interrupted suture with monofilament nylon sutures (conventional
      procedure). From January 2009, the 10-Fr silastic flexible drains were placed at
      the subcutaneous space and subcuticular suture using a monofilament absorption
      string was performed. A liquid tissue adhesive was used to seal the skin wound
      (revised procedure). There was no difference between the conventional group and
      the revised group in age and gender. Risk factors in two groups were not found
      the significant difference except diabetes mellitus. Incisional SSI was observed
      in 23 patients out of 72 patients (31.9%). There was no significant difference in
      incidence in clinicopathological factors. Only the revised procedure of wound
      closure significantly decreased 13.8% of incisional SSI rate from 44.2% in the
      conventional procedure. CONCLUSIONS: Our several changes of wound closure
      including tissue adhesive, subcuticular suture and subcuticular closed suction
      drainage reduced incisional SSI.

PMID- 24901142
TI  - Effects of 5-amino salicylic acid on the expression of multidrug resistance gene
      in ulcerative colitis.
AB  - BACKGROUND/AIMS: To study the effect of drugs on the expression of multidrug
      resistance gene in ulcerative colitis. METHODOLOGY: The expressions of multidrug
      resistance (MDR) 1 gene and its product P-Gp were detected by reverse
      transcription-polymerase chain reaction and immunohistochemistry to realize the
      impact of drugs on ulcerative colitis. RESULTS: MDR1 gene and P-Gp did not
      exhibit significant difference (P > 0.05) before and after amino salicylic acid
      drug treatment. Compared with the control group, their expressions before
      treatment in the ineffective corticosteroid- and immunosuppressant-treated groups
      did not exhibit significant difference (P > 0.05). Their pre- and post-treatment
      expressions in the ineffective groups were compared with those in the normal
      control group and in the effective group, and significant differences were
      observed (P < 0.05). CONCLUSIONS: 5-Amino salicylic acid drugs have little effect
      on the expression of MDR1 and its product P-Gp. The expressions of MDR1 and P-Gp
      were much higher in groups that showed ineffectiveness for corticosteroids and
      immunosuppressants after treatment.

PMID- 24901143
TI  - Intraperitoneal chemotherapy for peritoneal carcinomatosis improves efficacy with
      acceptable safety: results of 200 cycles for 41 patients.
AB  - BACKGROUND/AIMS: To investigate the efficacy and safety of intraperitoneal (IP)
      chemotherapy for peritoneal carcinomatosis (PC). METHODOLOGY: Forty-one PC
      patients received IP chemotherapy with carboplatin at 200 mg/m2 and docetaxel at
      60 mg/m2 at 21-day intervals. Major organ functions were monitored. Changes in
      ascites and serum tumor markers (TM) were recorded. The primary endpoint was
      overall survival COS) and the secondary endpoint was adverse event (AE). RESULTS:
      The patients received 200 cycles of IP chemotherapy, with a median of 5 IP
      chemotherapy cycles at the median duration of 5 months. The median follow-up was
      19.5 months. For 25 patients with ascites, 15 cases had significant improvement,
      9 had stable disease, and 1 had treatment failure. End-point events occurred in
      31 patients, including 26 deaths from gastrointestinal PC with a median OS of 8.4
      months (95%CI 4.6-12.2 months) and 5 deaths from other origins (median OS not
      reached). Multivariate analysis revealed the following independent OS-related
      factors: CC<1, primary tumor site, and decreases in CA125 and CEA for 2
      consecutive cycles. Grade III toxicities included 16 cycles of digestive AE and 8
      cycles of bone marrow suppression. CONCLUSIONS: IP chemotherapy improves OS for
      PC patients with acceptable safety.

PMID- 24901144
TI  - Comparisons of inflammatory cytokines expressions in drain after laparoscopic
      versus open surgery.
AB  - BACKGROUND/AIMS: Laparoscopic surgery reduces the risk of postoperative adhesion
      compared with open surgery. The aim of this study was to assess the advantage of
      laparoscopic surgery in terms of postoperative adhesion. METHODOLOGY: Eleven
      patients participated in this study (laparoscopic surgery: 6 patients, open
      surgery: 5 patients). Body temperature, heart rate, the duration until the first
      postoperative flatus and the beginning of diet were investigated on postoperative
      day 0, 1, 3, and 5, respectively. Serum level of WBC and CRP, PAI-1 and IFN-gamma
      level in the drainage tube were also measured at the same time. RESULTS: There is
      no significant difference between the two groups in body temperature. The
      laparoscopic group revealed significantly lower WBC on POD 0 and CRP on POD 1
      compared with the open group. PAI-1 was significantly lower on POD 3 and 5 in the
      laparoscopic group. IFN-gamma in the laparoscopic group tended to be suppressed
      compared with the open group. CONCLUSIONS: Laparoscopic surgery may decrease the
      risk of postoperative abdominal adhesion compared with open surgery by
      suppressing early postoperative inflammation.

PMID- 24901145
TI  - Increased apoptosis of regulatory T cells in Crohn's disease.
AB  - BACKGROUND/AIMS: Crohn's disease (CD) is characterized by a transmural often
      granulomatous Th1-driven inflammatory process hallmarked by an increased
      production of IL-12, TNF-alpha and IFN-gamma. Accumulating evidence suggests that
      the numerical defect within the regulatory T cell (Tregs) compartment might
      contribute to this imbalance between pro- and antiinflammatory factors. This
      study was aimed to investigate whether the numerical defect of Tregs observed in
      CD resulted from an increased apoptosis of these cells. METHODOLOGY: The
      cytometric analysis was performed to evaluate the percentage of CD4 + FOXP3 +
      Tregs in peripheral blood of 55 investigated subjects, as well as to estimate the
      rate of Treg apoptosis. RESULTS: The cytometric analysis showed a significantly
      lower percentage of Tregs in peripheral blood of CD patients compared with the
      healthy control group (P = 0.03) as well as an increased rate of apoptosis within
      this cell subpopulation (P = 0.000001). Interestingly, a significantly higher
      rate of Treg apoptosis was observed in female than male CD patients (P = 0.03).
      DISCUSSION: Current data suggest that CD is associated with a numerical
      deficiency of the Treg compartment. Presented study indicates that an increased
      apoptosis might contribute to this numerical deficiency. A higher rate of Tregs
      apoptosis found in female patients might suggest the involvement of hormonal
      factors and possibly contribute to the female predominance observed in CD as well
      as to the tendency of female patients to develop a more severe form of the
      disease.

PMID- 24901146
TI  - Role of vascular clamping in hepatic resection: a review.
AB  - Hepatic resection is usually a complicated surgical procedure. In the course of
      liver organ resection overwhelming safety measures are extremely important simply
      because this organ has parallel vascular source. Expensive machines are launched
      in schedule operative practice without the proper evidence of their
      efficaciousness or efficiency in excess of less complicated procedures.
      Intermittent clamping of 10 minutes could be accomplished in the affected person
      with disadvantaged liver organ performance for instance in cirrhosis. Blended
      utilization of a balloon occlusion catheter, electrocautery and/or ultrasonic
      coagulating shear and endo-GIA staplers, generally seem to preserve satisfactory
      homeostasis which helps prevent gas embolization in the course of laparoscopic
      hepatectomy in human beings. Selection of clamping is perfectly up to the
      surgeons. For minimal hepatic resection some experts do not implement any
      clamping strategy. Collaboration amongst specialists and anesthetists is
      significant to ascertain this challenge throughout resection.

PMID- 24901147
TI  - Acute Budd-Chiari syndrome associated with non-viral cryptogenic hepatocellular
      carcinoma: revisiting the 'chicken or the egg' theory.
AB  - Budd-Chiari syndrome is an eponym for "hepatic venous outflow tract obstruction".
      BCS left untreated has a high mortality rate. Diagnosis can be difficult because
      of the wide spectrum of presentation of the disease and the varying severity of
      liver damage. The onset of disease may be insidious, with a chronic, asymptomatic
      course, or also present on other occasions as an acute, life-threatening
      condition. In rare instances, BCS is associated with hepatocellular carcinoma
      (HCC), which may be both a cause and a consequence of BCS. Presented here is a
      case of acute, rapidly fatal severe BCS associated with HCC. The association
      between BCS and HCC in 'the chicken or the egg' analogy is revisited.

PMID- 24901148
TI  - Thirty-five consecutive pediatric living donor liver transplantation: experiences
      and lessons learned from a single center.
AB  - BACKGROUND/AIMS: In the last 10 years, the early patient outcome of liver
      transplantation in children have significantly improved. Now the overall outcomes
      of pediatric LT are promising. METHODOLOGY: In this study, we review the outcome
      of all pediatric liver transplants performed at our center and analyze our
      experiences with pediatric liver transplant. Of the 34 liver transplant
      recipients, 26 were highly urgent (19.7%). RESULTS: Actuarial patient survival
      rates at 6, 12, and 36 months was 82.9%, 79.8% and 72.2%, respectively.
      Indications for liver transplant were biliary atresia (n = 22), Wilson's disease
      (n = 4), glycogen storage disease (n = 3), portal vein cavernous transformation
      (PVCT) (n = 3), fulminant liver failure (n = 1), and cryptogenic cirrhosis (n =
      1). The main complications were surgical complications (including biliary
      complications, portal vein or arterial complications, intestinal perforation,
      postoperative bleeding, of which 20% required reoperation) and infections.
      Cyclosporine was the primary immunosuppressive agent used in 70.6% of patients,
      with a 26.5% incidence of acute allograft rejection within the first six months.
      One children underwent re-transplant as a result of hepatic artery thrombosis.
      Nine children died during followup. They were related to portal vein thrombosis
      (one), chronic rejection (one), sepsis (one), post-transplant lymphoproliferative
      disease (one) and so on. CONCLUSIONS: The overall outcomes of pediatric liver
      transplantation at our center are promising. Advances in post-transplant care and
      monitoring of the recipients, technical refinements enable these results.

PMID- 24901149
TI  - Chemoembolization for neuroendocrine liver metastasis.
AB  - The liver is the most common site for neuroendocrine tumor metastasis. The
      characteristic feature of these tumors is related to the secretion of
      biologically active compounds in large amounts. Systemic chemotherapy has limited
      success in treating patients with neuroendocrine liver metastasis. Surgical
      management remains the only potentially curative option for these patients.
      According to the high incidence of recurrence after surgery, the role of intra
      arterial therapy (IATs) in neuroendocrine tumor metastasis has been evolved. This
      review evaluates the potential role of IATs in the light of current literature.

PMID- 24901150
TI  - Long-term outcome of laparoscopic hepatectomy in patients with hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: The long-term prognosis for patients with hepatocellular
      carcinoma (HCC) who undergo laparoscopic hepatectomy has not been well compared
      with that for patients after open hepatectomy. METHODOLOGY: We analyzed patient
      survival (PS) and disease-free survival (DFS) of 310 consecutive patients who
      underwent primary hepatectomy between January 2001 and March 2010. The patients
      were divided into Group LAP (laparoscopic approach) (n = 24) and Group OPN (with
      open laparotomy) (n = 286). The median follow-up time was 60.9 months (range,
      12.0-123.9 months). RESULTS: The 5-, and 7-year PS rates of Group LAP were 87.9%,
      and 87.9%, and those of Group OPN were 82.2% and 69.3%, respectively (P =
      0.5638). The 5-, and 7-year DFS rates of Group LAP were 47.1%, and 31.4%, and
      those of Group OPN were 29.4%, and 24.3%, respectively (P = 0.4594). Laparoscopic
      hepatectomy in patients of Group LAP resulted in a better outcome of blood loss
      (P = 0.0314), operative time (P < 0.0001), and hospital stay (P = 0.0008).
      CONCLUSIONS: The long-term outcome of laparoscopic hepatectomy for patients with
      HCC was identified to be comparable to open hepatectomy with regard to PS and
      DFS. Laparoscopic hepatectomy is a promising therapeutic option for patients with
      HCC.

PMID- 24901151
TI  - Resveratrol inhibits VEGF gene expression and proliferation of hepatocarcinoma
      cells.
AB  - BACKGROUND/AIMS: Resveratrol is known to have potent anti-inflammatory and
      antioxidant effects and to inhibit platelet aggregation and growth of a variety
      of cancer cells. In the paper, we investigated the effects of Resveratrol (Res)
      on expression ofVEGF gene in human hepatocarcinoma cell cells and cell
      proliferation. METHODOLOGY: HepG2 cells were treated with different
      concentrations of Res (0, 10, 20, 40 micromol/L) and rent time (24, 48, 72h).
      Cell proliferation was examined by MTT method and the expression of VEGF gene was
      analyzed by RT-PCR and Western blot. RESULTS: Res could inhibit expression of
      VEGF gene, the inhibitory effect of Res increased with the increasing of
      concentration of Res and treatment time. CONCLUSIONS: Our results suggest that
      Res can significantly inhibit the proliferation of HepG2 cells and exerts an anti
      tumor effect by repressing the expression of VEGF gene.

PMID- 24901152
TI  - Percutaneous transhepatic portal vein stent placement can improve prognosis for
      hepatocellular carcinoma patients with portal vein tumor thrombosis.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis
      (PVTT) has an extremely poor prognosis. One reason is that portal hypertension
      may progress rapidly and intractable gastric/esophageal variceal hemorrhage may
      occur in PVTT cases. We studied whether a percutaneous transhepatic portal vein
      stent placement could improve the prognosis for HCC with PVTT. METHODOLOGY: Five
      cases of HCC with PVTT where portal hypertension had rapidly progressed were
      performed portal vein stenting. RESULTS: All cases had been classified into Child
      Pugh class C. Only one of them died of liver failure five months after stent
      placement, but two of the cases successfully avoided dying of liver failure and
      the other two cases are still alive with a hepatic functional reserve maintained.
      CONCLUSIONS: Although portal vein stent placement for HCC with PVTT is not by
      itself a therapy for PVTT, portal vein stent placement plays a prominent role in
      improving hepatic function reserve preventing fatal hepatic failures due to PVTT
      and gastric/esophageal variceal hemorrhage associated with portal hypertension.
      This leads to prolonged survival for HCC patients with PVTT. Further prospective
      trials including the appropriate timing of portal vein stent placement treatment
      will be needed for larger numbers of HCC patients with PVTT.

PMID- 24901153
TI  - Laparoscopic left lateral sectionectomy--the learning curve and the role of left
      hepatic inflow occlusion.
AB  - BACKGROUND/AIMS: To investigate the learning curve of laparoscopic left lateral
      sectionectomy (LLLS), and the role of left hepatic inflow occlusion (LHIO) in
      LLLS. METHODOLOGY: 41 consecutive cases of solid lesion in left lateral section
      underwent LLLS between August 2011 and August 2012. LHIO was conducted in 21
      cases. RESULTS: The overall median operative time and blood loss were 160 min
      (range, 80-290 min) and 80 mL (range, 20-00 mL), respectively. The median
      operative time and blood loss were significantly reduced in later 21 cases
      compared with early 20 cases (110 min vs. 195 min, 40 mL vs. 265 mL,
      respectively). Compared with the group of cases that did not undergo LHIO, the
      median operative time and blood loss were significantly reduced (130 min vs. 185
      min, 50 mL vs. 290 mL, respectively) in the group of cases that underwent LHIO,
      while the elevation of transaminase at postoperative day 2 and day 5 were of no
      significant difference between these two groups. CONCLUSIONS: A smooth learning
      curve can be achieved for LLLS, LHIO was associated with reduced operative time
      and blood loss without increasing the risk of postoperative liver function
      impairment.

PMID- 24901154
TI  - High-sensitivity C-reactive protein is a strong predictor of non-alcoholic fatty
      liver disease.
AB  - BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is a clinical term
      that covers simple fatty liver (SFL) and non-alcoholic steatohepatitis (NASH),
      and high-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation. The
      aim of the present study was to investigate the relationship between steatosis
      and hs-CRP in patients with ultrasonographically verified NAFLD. METHODOLOGY: We
      examined 296 consecutive patients. NAFLD was detected by ultrasound (US).
      Patients with NAFLD who had an alanine aminotransferase (ALT) level of > 40 IU/mL
      were considered to have NASH and those with normal liver function test results
      were considered to have SFL. Patients who did not have NAFLD constituted the
      control group. The SFL, NASH and control groups were compared in terms of hs-CRP
      levels. RESULTS: Of 296 patients, 86 had normal hepatic US findings and 210 had
      hepatosteatosis. Hs-CRP levels were higher in patients with NAFLD as compared to
      the control group (0.68 mg/ dL vs. 0.34 mg/dL, respectively; P < 0.05). There was
      no significant difference between patients with SFL and NASH in terms of hs-CRP
      levels (P > 0.05). Logistic regression analysis revealed that hs-CRP was a strong
      predictor of NAFLD (odds ratio: 6.04; 95% confidence interval: 2.08-17.74).
      CONCLUSIONS: hs-CRP can be used as a non-invasive marker of NAFLD as it was found
      to be a strong predictor of NAFLD in this study.

PMID- 24901155
TI  - Immunohistochemical demonstration of transferrin receptor 1 and 2 in human
      hepatocellular carcinoma tissue.
AB  - BACKGROUND/AIMS: Recent studies have confirmed that iron overload is involved not
      only in liver carcinogenesis, but in its progression. Results in studies using
      liver cancer cell lines have suggested a relationship between transferrin
      receptor (TfR) expression and liver carcinogenesis, but TfR expression has not
      yet been analyzed in human hepatocellular carcinoma (HCC) tissues. METHODOLOGY:
      We immunohistochemically assessed the expression of TfR1 and TfR2 in tumor
      tissues and adjacent non-tumorous liver tissues from 41 HCC patients who
      underwent partial hepatectomy. We evaluated uptake of iron in hepatocytes and HCC
      cells using iron staining. RESULTS: The expression TfR was significantly higher
      in HCC samples than in adjacent non-tumor tissue (p < 0.001). TfR expression was
      significantly related to serum alpha-fetoprotein (p < 0.05) and des-gamma carboxy
      prothrombin (p < 0.05) concentrations. We also found iron deposition in non-tumor
      tissue from 25 patients, but in only two HCC samples, consistent with findings
      that hepatocellular iron uptake decreases with liver carcinogenesis. CONCLUSIONS:
      We investigated the expression of TfR1 and TfR2 in human HCC tissues by
      immunohistochemistry, the first report demonstrating TfR2 expression
      immunohistochemically in human HCC. These results suggest that TfR is expressed
      in response to iron deficiency during liver carcinogenesis.

PMID- 24901156
TI  - Comparison of post-operative short-term and long-term outcomes between occult and
      frank biliary rupture of hydatid disease.
AB  - BACKGROUND/AIMS: Intrabiliary rupture (IBR) is the most common and serious
      complication of hepatic hydatid cyst (HHC). The aim of this retrospective study
      was to evaluate postoperative short-term and long-term outcome of patients
      treated surgically for complicated liver hydatid cysts. METHODOLOGY: A total of
      168 cases with biliary communication of hydatid cyst were analyzed
      retrospectively, 92 of which had biliary communication with an occult rupture
      while 76 (45.23%) had Frank biliary rupture. Preoperative demography, ultrasonic
      cyst features, postoperative short-term complications, postoperative follow-up
      (long-term) complications and hospital stay were recorded and analyzed. RESULTS:
      There were no differences in the demographic characteristics and preoperative
      cyst features in Frank and occult group. Compared with the Frank group 9.34 +/-
      1.25 (days), the postoperative stay in occult 6.97 +/- 1.62 (days) were
      relatively shorter. The incidence of overall postoperative short-term
      complications and long-term complications were insignificantly lower in occult
      group (22.82%) than Frank group (30.26%) with P = 0.275. Incidence of
      postoperative biliary leakage 8 (8.69%) and abscess 5 (5.43%) in occult group was
      insignificantly more common than Frank rupture with biliary leakage 5 (6.5%) and
      abscess 2 (2.63%) with P value was 0.609 and 0.365 respectively while long-term
      biliary stricture is significantly greater in Frank group (10.52%) then occult
      group (0%) with P = 0.01. CONCLUSIONS: Frequency of occurrence of postoperative
      short-term complications biliary fistula and abscess is relatively more common in
      occult rupture with transcystic drain due to its indolent course, inability to
      find and suture the rupture orifice, and incomplete decompression while biliary
      stricture is significantly more common in Frank group due to its involvement of
      major bile ducts.

PMID- 24901157
TI  - Comparison between percutaneous radiofrequency ablation and surgical hepatectomy
      focusing on local disease control rate for colorectal liver metastases.
AB  - BACKGROUND/AIMS: Therapeutic efficacy of radiofrequency ablation (RFA) for
      colorectal liver metastases (CRLM) was compared with hepatic resection (HR),
      focusing on local disease control rate as well as risk factors of recurrence and
      patients survival. METHODOLOGY: From April 2002 to March 2012, 32 patients
      underwent RFA and 60 patients underwent HR for CRLM. The rate of local recurrence
      along the ablated or resected margin was evaluated in these patients. RESULTS:
      The local recurrence was seen in 8 patients (13.3%) after HR, and 15 (46.9%)
      after RFA. Multivariate analysis of all patients revealed that RFA as an initial
      therapy (P < 0.001), venous invasion liver metastases (P = 0.049) were
      independent risk factors for local recurrence. Subgroup analysis showed that
      local recurrence rate after RFA was significantly higher than that after HR in
      patients with tumors 20 mm or larger (P < 0.001), while there was no significant
      difference in local recurrence rate between RFA and HR in patients with tumors
      less than 20 mm (P = 0.676). CONCLUSIONS: RFA showed a high risk of local
      recurrence in comparison to HR especially in patients with tumors larger than 20
      mm. Indication of RFA should be restricted drastically considering the limitation
      of efficacy.

PMID- 24901158
TI  - Interleukin-10 gene promoter polymorphism and susceptibility to liver cirrhosis.
AB  - BACKGROUND/AIMS: Liver cirrhosis is the end-stage of various liver diseases,
      which has a poor prognosis and determined by deterioration of hepatic functional
      capacity and consecutive development of hepatic complications. We investigated
      the role of IL-10-592 A/C, IL-10-819 C/T and IL-10-1082 A/G gene polymorphisms on
      the development of liver cirrhosis. METHODOLOGY: A 1:2 matched case-control study
      was conducted, including 266 patients from 302 Military Hospital. Genotyping of
      IL-10-592 A/C, IL-10-819 C/T and IL-10-1082 A/G were performed in a 384-well
      plate format on the Sequenom MassARRAY platform. RESULTS: Multivariate regression
      analyses showed that subjects carrying the IL-10-592 CC variant had a significant
      increased risk of liver cirrhosis (OR: 1.83, 95% Cl: 1.10-3.03), and IL-0-592 A/C
      showed a significant increased risk in recessive model (OR: 1.97, 95% CI: 1.15
      3.45). We found those carrying IL-10-592 CC genotype had a heavy increased risk
      of liver cirrhosis in those with positive chronic hepatitis B, with an OR (95%
      CI) of 2.46 (1.35-4.42), and a significant interaction was observed between the
      IL-10-592 A/C genotype and chronic hepatitis B infection (P = 0.036). Those
      carrying IL-10-819 C/T and IL-10-1082 A/G variants had non-significant increased
      risk of liver cirrhosis. CONCLUSIONS: Our study demonstrates that IL-10-592A/C
      gene polymorphism would enhance the risk for liver cirrhosis, and this gene
      variant has interaction with chronic hepatitis B infection in Asian population.

PMID- 24901160
TI  - Single-incision clipless laparoscopic total colectomy.
AB  - Although single incision laparoscopy surgery (SILS) has been applied to various
      kinds of surgical diseases, there have few reports on total colectomy by SILS. A
      3-cm incision was placed in the umbilical fossa, through which a SILS port was
      placed. And this laparoscopic procedure was started as follows: Firstly, the
      greater omentum was divided. After the division was extended to both splenic and
      hepatic sides, each flexure of the colon was taken down. A mesocolon window was
      created below the descending to horizontal portion of the duodenum. The mesocolon
      including vessels from the left side of the window to the sigmoid colon was
      incised by LigaSure without clips. After intestinal transection was performed at
      the upper side of the rectum with a stapler, ileo-rectal anastomosis was
      performed by the double stapling technique. Between 2010 and 2012, eight
      consecutive patients underwent this procedure. The mean operative time was 228.1
      (range 205-255) min, the mean operative blood loss was 64.0 (range 0-310) mL, the
      mean hospitalization after surgery was 10.8 (range 10-12) days, and no
      postoperative complications were encountered. Single incision clipless
      laparoscopic total colectomy using our original procedure seems to be feasible
      and safe.

PMID- 24901159
TI  - Assessment of angiogenesis of hepatocellular carcinoma using dynamic contrast
      enhanced MR and histopathologic correlation in an experimental rat model.
AB  - BACKGROUND/AIMS: To assess the perfusion parameters and angiogenesis of HCC using
      dynamic contrast enhanced(DCE) MR and to correlate it with histopathologic
      findings in an experimental rat model. METHODOLOGY: Twenty rats were continuously
      infused with diethylnitrosamine (DEN) for tumor induction. After 32 to 36 weeks
      of DEN treatment, the rats underwent MRI of the liver with a 3-T MR imaging
      system. Perfusion parametric maps and perfusion parameters such as, time to peak
      (TTP) and peak enhancement (PE) were obtained by using a commercially available
      software package. The nodules were correlated precisely to DCE MR images.
      RESULTS: A total of 13 nodules were found in 12 rats; 5 dysplastic nodule (DN)s
      were identified in 5 rats and 8 HCCs (3 Edmonson grade I, 2 Edmonson grade I-II,
      3 Edmonson grade II) were found in 7 rats. There were significant differences in
      mean values of PE and HPH (histogram peak height) of PE between DN and HCC. Mean
      value and HPH of PE showed statistically significant correlation with tumor
      grade. CONCLUSIONS: There were significant differences in perfusion parameters
      between DN and HCC. DCE MR imaging can be used in the differential diagnosis and
      management of liver disease in hepatocarcinogenesis.

PMID- 24901161
TI  - The mean platelet volume is a potential biomarker for cirrhosis in chronic
      hepatitis B virus infected patients.
AB  - BACKGROUND/AIMS: In recent years, a great interest has been dedicated to the
      development of noninvasive predictive models to substitute liver biopsy for
      cirrhosis assessment and follow-up. Our aim was to provide a simple marker for
      predicting liver cirrhosis in chronic hepatitis B virus (HBV)-infected patients
      based on routinely available clinical parameters. METHODOLOGY: Three hundred and
      fifty-four patients with chronic hepatitis B, including 144 with cirrhosis, 210
      without cirrhosis, and 68 healthy controls were enrolled in the study. During the
      study, a blood sample was collected from all cases to examine liver function,
      renal function, international normalized ratio (INR) and routine hematological
      testing. RESULTS: We demonstrated that in the cirrhosis group, mean platelet
      volume (MPV) values were significantly increased compared with healthy controls
      and non-cirrhosis group. Multivariate analysis demonstrated that MPV, total
      bilirubin (TB) and INR were independent predictors for cirrhosis (both P < 0.01).
      CONCLUSIONS: MPV is a simple and non-invasive routine laboratory parameters and
      elevated MPV level might be an independent predictor for cirrhosis in patients
      with chronic HBV infection.

PMID- 24901163
TI  - Mesopancreas first dissection during pancreaticoduodenal resection: selective
      approach or paradigm?
AB  - BACKGROUND/AIMS: Pancreaticoduodenal resection is the procedure of choice for
      tumors of the pancreatic head and periampullary region. During
      pancreaticoduodenectomy resection, early neck division may be impossible or
      inadequate in case of hepatic artery anatomic variants, suspected involvement of
      the superior mesenteric vessels or intraductal papillary mucinous tumors. This
      paper aims to reveal the effectiveness of a modified posterior approach
      pancreaticoduodenectomy in selected indications and to assess the preliminary
      results. METHODOLOGY: We describe our early approach to the retropancreatic
      vasculature during pancreaticoduodenal resection by mesopancreas first dissection
      before any pancreatic or digestive transection. RESULTS: We used this approach in
      45 patients. Thirty had hepatic artery anatomic variant. Hepatic artery
      reconstruction was required in 2 cases. In nine patients with intraductal
      papillary mucinous tumors the pancreaticoduodenal resection was extended to the
      body in 6 and totalized in 3 patients. In six patients with adenocarcinoma
      involving the portomesenteric axis, venous resection and reconstruction was
      necessary. CONCLUSIONS: Mesopancreas first dissection is useful tool in selected
      cases of pancreaticoduodenal resection to improve safety and radicality of the
      procedure.

PMID- 24901162
TI  - Management of Budd-Chiari: a single-center experience of 280 cases.
AB  - OBJECTIVE: Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder
      secondary to hepatic venous outflow obstruction. How to manage this complex
      disease has haunted many surgeons. The aim of this study is to investigate the
      treatment of Budd-Chiari syndrome in our hospital. METHODS: The clinical data of
      280 BCS patients were analyzed retrospectively in our hospital between July 2000
      and March 2013. RESULTS: The total effective rate was 90% (252/280). The rate of
      mortality was 7.14% (20/280), the rate of complication was 17.14% (48/280). We
      carried out followup in 198 cases from 6 months to 10 years, the rate of
      recurrence was 6.07% (12/198). CONCLUSIONS: Treatment of BCS need to get a
      corrective diagnosis and classification at first, then select corrective methods
      of treatment based on different pathological change of IVC and main hepatic vein.

PMID- 24901164
TI  - A novel triple secured technique for pancreatic reconstruction following
      pancreaticoduodenectomy for a soft pancreas.
AB  - BACKGROUND/AIMS: Soft pancreases are susceptible to developing pancreatic fistula
      following pancreaticoduodenectomy. To reduce the incidence of pancreatic fistula
      after pancreaticoduodenectomy in patients with a soft pancreas, we developed a
      triple secured technique. In this study, we describe the details of this
      technique and also report on the postoperative outcomes. METHODOLOGY: The triple
      secured technique employed an ultrasonic dissector for pancreatic transection
      with skeletonizing and ligating of the small pancreatic branch ducts, duct
      invagination or duct-to-mucosa anastomosis for main pancreatic duct management,
      and, finally, four large stitches between the pancreatic stump parenchyma and the
      jejunal seromuscular layer to prevent minor pancreatic leakage. A total of 28
      consecutive patients with a soft pancreas who underwent pancreaticoduodenectomy
      using our technique were included in this study. RESULTS: Postopetrative
      complications occurred in 16 patients. Grade B pancreatic fistula developed in 6
      patients. However, no grade C pancreatic fistula occurred in this series. Neither
      any reoperation nor in-hospital mortality was observed in this series.
      CONCLUSIONS: Our triple secured technique after pancreaticoduodenectomy was
      feasible and safe, with an acceptable rate of grade B pancreatic fistula and no
      grade C pancreatic fistula for patients with a soft pancreas.

PMID- 24901165
TI  - Placement of a duodenal stents bridge the duodenal papilla may predispose to
      acute pancreatitis.
AB  - BACKGROUND/AIMS: To retrospective evaluate the incidence, predictive factors, and
      management of acute pancreatitis after placement of duodenal stent in patients
      with malignant gastroduodenal obstruction. METHODOLOGY: Among 242 patients with
      symptomatic malignant gastroduodenal obstruction successfully treated with
      duodenal stent placement, acute pancreatitis occurred in 10 (4.1%) of the
      patients 1-7 days after stent placement. The variables were analyzed. Univariate
      and multivariate analysis was performed to evaluate factors predictive of acute
      pancreatitis. Management of acute pancreatitis also was evaluated. RESULTS: All
      patients with acute pancreatitis were presented with abdominal pain and
      distention with vomiting 1-7 days after stent placement, in which 7 patients
      developed acute janudice. Four patients were cured by fasting and intravenous
      nutrition, and the remaining 6 cases were managed with percutaneous
      cholangiography and drain placement (PTCD). Univariate analysis showed acute
      pancreatitis was associated with location in the descending duodenum (p = 0.001)
      and stent bridge the duodenal papilla (p < 0.001). Multivariate analysis
      exhibited that the presence of stent bridged the duodenal papilla (odds ratio
      (OR), 18.48; 95% CI, 2.298-148.48; p = 0.006) was independent predictors of acute
      pancreatitis. CONCLUSIONS: Acute pancreatitis is an uncommon early complication
      of placement of duodenal stents in patients with malignant gastroduodenal
      obstruction. Acute pancreatitis occurred most commonly in descending duodenum,
      and in patients with stent bridged the duodenal papilla. Stent bridged the
      duodenal papilla may be the most important predictors for acute pancreatitis.
      Acute pancreatitis can be managed conservatively or by PTCD when developed to
      acute jaundice.

PMID- 24901166
TI  - Alteration of strain ratio evaluated by transabdominal ultrasound elastography
      may predict the efficacy of preoperative chemoradiation performed for pancreatic
      ductal carcinoma: preliminary results.
AB  - BACKGROUND/AIM: We evaluated the usefulness of ultrasound-elastography (US
      elastography) for prediction of therapy effect by measuring strain ratio (SR).
      METHODOLOGY: Consecutive patients with resectable pancreatic ductal carcinoma who
      underwent US-elastography before and after neoadjuvant chemoradiation were
      included. Patients were classified into either response group or non-response
      group according to the histological evaluation of resected specimens. Serum
      carbohydrate antigen 19-9 (CA19-9), SR, and maximum standard uptake value
      (SUVmax) obtained from 18F-fuluoro-deoxy-D-glucose positron emission tomography
      and computerized tomography were measured before and after chemoradiation.
      Alteration rate of each parameter was compared between response group and non
      response group. RESULTS: Seven patients met the inclusion criteria. One patient
      was excluded from pancreatectomy because liver metastasis was found by
      laparotomy. Serum CA19-9 was not elevated for 2 patients throughout the
      chemoradiation. Three patients were classified into response group and the
      remaining three into non-response group. Alteration rate of CA19-9 and SR was
      shown to be grater in response group (26.83 +/- 19.69 vs. 4.87 +/- 4.25, and 3.61
      +/- 2.40 vs. 1.39 +/- 0.20, respectively), whereas that of SUVmax was not (1.56
      +/- 0.43 vs. 2.11 +/- 0.10). CONCLUSIONS: Increase rate of SR may predict the
      therapy effect of neoadjuvant chemoradiation for patients with pancreatic ductal
      carcinoma, especially for patients without elevation of tumor markers.

PMID- 24901167
TI  - A reliable pancreaticojejunal anastomosis with V-Loc 180 wound closure device for
      soft pancreatic stump.
AB  - BACKGROUND/AIMS: Although mortality rates decreased in recent years,
      pancreaticoduodenectomy is still associated with high morbidity rates. Pancreatic
      fistula is the leading cause of morbidity after pancreaticojejunal anastomosis
      and commonly occurs in soft pancreas. The objective of this study is to compare
      outcomes of conventional modified invaginated end to side pancreaticojejunostomy
      with a new practical method using V-Loc 'rM 180 wound closure device in soft
      pancreas. METHODOLOGY: Between December 2011 and August 2013, a total of 90
      pancreaticoduodenectomy procedures were performed in our hospital. 28 of them
      were defined as soft pancreas according to attending surgeon and included in this
      study. Patients were divided into two groups consecutively and analysed for
      postoperative pancreatic fistula (POPF) rate, length of stay, operation time,
      cost and particular duration of anastomosis. Pancreatic fistulas were classified
      according to International Study Group on Pancreatic Fistula (ISGPF) definition.
      RESULTS: 1 grade A and 2 grade B fistulas appeared in V-Loc group (Group 1),
      whereas 1 grade A, 2 grade B and 1 grade C fistulas appeared in conventional
      anastomosis group (Group 2). CONCLUSIONS: Pancreaticojejunostomy with V-Loc
      suture is a convenient method in soft pancreas and can be performed safely.

PMID- 24901168
TI  - Short-term outcome of new end-to-side inserting pancreatico-jejunostomy without
      stiches on the pancreatic cut end.
AB  - BACKGROUND/AIMS: Post-operative leakage from pancreatic anastomosis remains an
      important cause of morbidity in pancreaticoduodenectomy. It also contributes to
      prolonged hospitalization and mortality. We have developed a new inserting end-to
      -side pancreatico-jejunostomy without stiches on the pancreatic cut end or
      pancreatic duct. METHODOLOGY: In this novel anastomosis technique, the pancreatic
      stump is first sunk into jejunum deeply in an end-to-side manner and tightened
      with a purse string in the bowel serosa. The pancreatic stump could be inserted
      completely inserting into the jejunum, independent of the size of the pancreas
      and jejunum. We performed this new anastomosis to 21 patients prospectively in
      Kumamoto University Hospital from April to October in 2012. RESULTS:
      Postoperative pancreatic fistula was not observed at all in the 21 patients.
      There was no hospital death, whereas 6 patients developed postoperative
      complications. Importantly, one patient developed hemorrhage from pancreatic cut
      end into the jejunum. CONCLUSIONS: This new method would be expected to minimize
      leakage from pancreaticojejunostomy. Further studies should be planned in a
      randomized controlled trial compared with another traditional pancreatico
      jejunostomy.

PMID- 24901169
TI  - Comparison of standard laparoscopic distal pancreatectomy with minimally invasive
      distal pancreatectomy using the da Vinci S system.
AB  - BACKGROUND/AIMS: Minimally invasive procedures for pancreatic pathologies are
      increasingly being used, including distal pancreatectomy. This study aimed to
      assess the indications for and outcomes of the da Vinci distal pancreatectomy
      procedure. METHODOLOGY: We reviewed the medical records of patients who underwent
      pancreatic head resection from April 2009 to September 2013. Four patients (mean
      age, 52.7 years) underwent da Vinci distal pancreatectomy and 10 (mean age, 68.0
      +/- 12.1 years) underwent laparoscopic distal pancreatectomy. RESULTS: The mean
      surgical duration was 292 +/- 153 min and 306 +/- 29 min, the mean blood loss was
      153 +/- 71 mL and 61.7 +/- 72 mL, and the mean postoperative length of stay was
      24 +/- 11 days and 14 +/- 3 days in the da Vinci distal pancreatectomy and
      laparoscopic distal pancreatectomy groups, respectively. One patient who
      underwent da Vinci distal pancreatectomy developed a pancreatic fistula, while 2
      patients in the laparoscopic distal pancreatectomy group developed splenic
      ischemia and gastric torsion, respectively. CONCLUSIONS: Laparoscopic and robotic
      pancreatic resection were both safe and feasible in selected patients with distal
      pancreatic pathologies. Further studies are necessary to clarify the role of
      robotic surgery in the advanced laparoscopic era.

PMID- 24901170
TI  - Endoscopic drainage treatment of pancreatic pseudocysts.
AB  - BACKGROUND/AIMS: This study presents the experience of its authors with
      endoscopic drainage treatment of pancreatic pseudocysts. The first part of the
      study offers a literature overview of the basic knowledge of pancreatic
      pseudocysts. The authors gradually deal with the individual types of pancreatic
      pseudocysts, the clinical picture, complications and diagnostics. Within the
      bounds of differential diagnostics the authors stress mainly the necessity of
      differentiating pancreatic pseudocysts from cystic tumors and benign cysts.
      Special attention is dedicated to various modalities of pancreatic pseudocyst
      treatment. The second part of the study presents the authors' own results of the
      endoscopic drainage treatment of pancreatic pseudocysts. METHODOLOGY: Results of
      endoscopic drainage treatment of pancreatic pseudocysts, which is one of
      significant possibilities of treatment of these conditions, are presented.
      RESULTS: This method was used to treat 33 patients (24 men and 9 women) from
      September 2007 to March 2009. Endoscopic drainage of pancreatic pseudocysts was
      performed 4 times transduodenally a 29 times transgastrically, namely in 6 cases
      under endosonographic guidance and in 27 cases by a duodenoscope after
      endosonographic targeting. CONCLUSIONS: The authors conclude that endoscopic
      drainage is an effective method of pancreatic pseudocyst treatment.

PMID- 24901171
TI  - Two-layer challenge test as an assessment to predict islet graft function.
AB  - BACKGROUND/AIMS: To investigate graft viability assessment before transplantation
      using 31P-Nuclear Magnetic Resonance (NMR) spectroscopy combining a two-layer old
      storage method (TLM). METHODOLOGY: Rat pancreases were divided into three groups
      and respectively subjected to 0 (group 1), and 30 minutes (group 2) of warm
      ischemia (WI) before procurement. Pancreases were digested and pancreatic digest
      tissues were preserved for 3 h using TLM. 31P-NMR spectroscopy was used to
      measure ATP levels of digest tissue. After TLM, the ratio of beta-adenosine
      triphosphate to phosphate monoester (betaATP/PME) obtained by 31P-NMR
      spectroscopy was evaluated. Isolated islets were assessed for yield and in vivo
      function separately using nude mice. RESULTS: The betaATP/PME ratios were 0.11 +/
      0.04, and 0.03 +/- 0.01 in groups 1 and 2, respectively (P < 0.05). Islet yields
      (IEQ/pancreas) were significantly less in group 3 (P < 0.05) and the cure rate
      after transplantation of 200 islets to athymic nude mice were 100% (7/7), and 0%
      (0/7) in groups 1 and 2, respectively. We regard groups 1 as viable group and
      group 2 as non-viable group. The viable groups and the non-viable group were
      clearly distinguished by betaATP/PME ratios. CONCLUSION: 31P-NMR spectroscopy
      combining TLM provided an objective and rapid means to assess severity of islet
      graft damage prior to transplantation in the rat model.

PMID- 24901172
TI  - The variation of expression of CD4+ CD25+ Foxp3+ regulatory T cells in patients
      with Helicobacter pylori infection and eradication.
AB  - BACKGROUND/AIMS: H. pylori persists for the virtual life of its host. Recent
      studies suggested that CD4 CD25+ regulatory T cells may be involved in this
      process. However, the alteration of CD4+ CD25+ regulatory T cells after
      eradication of H. pylori remains a question. METHODOLOGY: By using biopsies from
      45 H. pylori-positive patients and the ones after eradication of H. pylori and 35
      H. pylori-negative adults, real-time PCR and general PCR were used to quantify
      the expression of Foxp3 mRNA. IHC was used to semi- quantify the number of CD4+
      CD25+ T cells in gastric mucosa. RESULTS: We found that proportion ofCD25+ T cell
      in CD4+ T cells accounted for 0.739% in H. pylori-negative individuals, while it
      was accounted for 5.012% in H. pylori-positive patients. After eradication of H.
      pylori, proportion of CD25+ T cell in CD4+ T cells declined (P mRNA significantly
      decreased (P < 0.01) in gastric mucosa of patients after eradication of H.
      pylori. CONCLUSIONS: CD4+ CD25+ regulatory T cells decreased in gastric mucosa
      when patients received eradication of H. pylori. Eradication of H. pylori results
      in the significant decrease of Foxp3 mRNA in gastric mucosal, or using the drugs
      of anti-H. pylori induce the reduction of gastric mucosal Foxp3 mRNA expression,
      which is the a key regulatory gene for the development and function of CD4+ CD25+
      regulatory T cells, thus contributing to the eradication of H. pylori. All the
      data offer new possibilities that Foxp3 gene may be the new target of
      immunization intervention strategies for eradication of H. pylori.

PMID- 24901173
TI  - Simple prognostic indicators using macroscopic features and age in advanced
      gastric cancer.
AB  - BACKGROUND/AIM: Macroscopic features and age may be important prognostic factors
      that discriminate survival among clinical conditions requiring different
      therapeutic strategies of advanced gastric cancer (AGC), and this study aimed to
      identify their clinical relevance. METHODOLOGY: A total of 232 AGC patients who
      had Surgical T2b or beyond was enrolled to identify clinical indicators,
      including macroscopic features in combination with age. RESULTS: Macroscopic
      features were divided into 3 categories (types I/II/V, III, and IV), which
      included stage IV in 24%, 53%, and 72% (P < 0.0001), respectively. Macroscopic
      features (P < 0.0001), histological features (P = 0.025), and pathological
      infiltration type (P = 0.0003) were all univariate prognostic factors, as well as
      stage (P < 0.0001) and age (P = 0.009). However, the multivariate proportional
      hazards model found that macroscopic features (P = 0.0013) and age (P = 0.0091)
      were the only factors independent of stage (P <0.0001). Both factors clearly
      classified the patients into 4 groups (young type 1/II/V (group 1), elderly type
      I/II/V (group 2), type III and young type IV (group 3), and elderly type IV
      (group 4) with different prognoses. CONCLUSIONS: Macroscopic features and age
      were simple indicators of prognosis in AGC. Both factors may have great potential
      to develop prognostic categories that effectively classify AGC into categories
      requiring different therapeutic strategies.

PMID- 24901174
TI  - Prognostic value of matrix metalloproteinase-9 in gastric cancer: a meta
      analysis.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the effect of matrix
      metalloproteinase-9 overexpression on clinical outcome of gastric cancer using a
      meta-analysis. METHODOLOGY: Relevant studies concerning the association between
      Matrix metalloproteinase-9 expression and survival of patients with gastric
      cancer were collected from electronic databases. Hazard ratios (HRs) with 95%
      confidence intervals (Cls) were calculated to estimate the association. Subgroup
      analysis was calculated to evaluate potential sources of heterogeneity. Besides,
      we also assessed the relationship between Matrix metalloproteinase-9 level and
      relevant clinicopathological parameters by estimating the Odds ratios (ORs) with
      95% Cls. RESULTS: Ten studies with 1,478 patients were included to perform a meta
      analysis of the survival results. Pooled HRs indicated that MMP-9 overexpression
      had a negative impact on the over survival (OS) of patients with gastric cancer
      (HR = 1.69, 95% Cl: 1.29-2.23, P = 0.00), without significant heterogeneity (chi2
      = 14.17, I2 = 36.5%, P = 0.117). Similarly, high level of MMP-9 tended to be
      correlated with lymph node metastasis (OR = 1.91, 95% Cl: 1.40-2.59, P < 0.05)
      and presence of vascular invasion (OR = 2.64, 95% CI: 1.52-4.59, P <0.05).
      CONCLUSIONS: This meta-analysis shows that Matrix metalloproteinase-9
      overexpression is a poor prognostic factor in patients with gastric cancer.
      However, larger scale and randomized studies are needed to confirm its potential
      clinical value.

PMID- 24901175
TI  - Light blue crest and ridge/villous patterns in the uninvolved gastric antrum by
      magnifying NBI endoscopy correlate with serum pepsinogen and gastric cancer
      occurrence.
AB  - BACKGROUND/AIMS: Combining the magnifying endoscopy and the narrow-band imaging
      (NBI) system is an endoscopic imaging technique for the enhanced visualization of
      mucosal microscopic structure and capillaries of the superficial mucosal layer.
      Light blue crest (LBC) and, ridge/villous pattern have been thought to be
      suggestive signs for gastric intestinal metaplasia (IM) of magnifying NBI
      endoscopy. Since the IM is related to gastric cancer risk (GC), the prevalence of
      LBC and ridge/villous pattern in the nonneoplastic gastric antrum was examined in
      relation to gastric cancer (GC) risk and serological severity of gastritis.
      METHODOLOGY: In 100 subjects including 13 GC patients, gastric mucosal pattern
      were examined using magnifying NBI. The mucosal patterns in the antrum were
      classified according to the presence of LBC or ridge/villous pattern. Serum
      pepsinogen (PG) levels were also examined. RESULTS: The sensitivity and
      specificity for predicting IM was the best when LBC and ridge/villous patterns
      were combined (sensitivity 95.2%, specificity 98.7%). Both LBC and ridge/villous
      pattern showed lower serum PGI and PGI/II ratio than those without (P = 0.046,
      0.0005, respectively.) In particular, PGI/II ratio was lowest in ridge/villous
      pattern. The LBC and ridge/villous pattern showed higher incidence of all GC and
      diffuse GC compared to those without (P = 0.002, 0.002, respectively).
      CONCLUSIONS: LBC and ridge/villous pattern in uninvolved gastric antrum by
      magnifying NBI endoscopy are useful signs for predicting gastric atrophy in the
      entire stomach and GC risk.

PMID- 24901176
TI  - No inverse relationship between Helicobacter pylori infection and adult asthma
      with peptic ulcer disease.
AB  - BACKGROUND/AIMS: Inverse correlation between childhood-onset asthma and human
      gastric Helicobacter pylori (H. pylori) infection exists. To investigate whether
      adult asthma patients with peptic ulcer disease demonstrated lower rates of H.
      pylori infection. METHODOLOGY: Asthma patients were identified from records of
      inpatient treatments or from 3 or more ambulatory care claims using the
      International Classifications of Diseases, Revision 9, Clinical Modification (ICD
      9-CM) diagnosis code: 493. To be defined as a non-asthma patient, a person cannot
      have the code ICD-9-CM: 490-494, and 496 in inpatient records or in the
      ambulatory care claims. The sample included 2,894 H. pylori-positive patients
      with peptic ulcers and 522 H. pylori-negative patients with peptic ulcers. A
      logistic regression model was used to calculate the odds ratio and a 95%
      confidence interval. RESULTS: Asthma patients with peptic ulcers included 74 H.
      pylori-positive and 21 H. pylori-negative. Non-asthma patients with peptic ulcers
      comprised 2,820 H. pylori-positive and 501 H. pylori-negative. Based on logistic
      regression analysis, adult asthma patients with peptic ulcers (OR = 0.71, P =
      0.187) demonstrated similar H. pylori infection rates, compared to adult non
      asthma patients with peptic ulcers. CONCLUSIONS: Our data show no inverse
      relationship between Helicobacter pylori infection and adult asthma with peptic
      ulcers.

PMID- 24901177
TI  - Multivariate analysis of prognostic factors in 549 patients undergoing surgical
      treatment of gastric cancer.
AB  - BACKGROUND/AIMS: Gastric cancer is a common malignancy with high mortality rate,
      and surgical resection is the primary treatment. METHODOLOGY: A retrospective
      analysis of patients who received surgical treatment for primary gastric cancer
      from January 2006 to December 2010 was performed. Cox univariate and multivariate
      analyses were performed to determine factors associated with decreased survival.
      RESULTS: A total of 549 patients were included in the analysis (421 men and 128
      women) with a mean age of 59.5 years (range, 21-81 years). Radical resection was
      performed in 496 patients, including D1 resection in 72 cases (14.5%), D2
      resection in 380 cases (76.6%), and D3 resection in 44 cases (8.9%). The follow
      up ranged from 3 to 67 months, during which 368 patients were alive or censored
      and 181 patients died. The overall 6-month and 1-, 3-, and 5-years survival rates
      were 89.8%, 80.8%, 58.9%, and 49.7% respectively. Multivariate analysis indicated
      that tumor size > 5 cm, increasing TNM stage, no resection, receiving
      perioperative blood transfusion, serum albumin <37 g/L, and not receiving
      postoperative comprehensive treatment (Chinese medicine, chemotherapy,
      immunotherapy) were associated with decreased survival. CONCLUSIONS: Tumor size,
      TNM stage, extent of resection, serum albumin level, and comprehensive treatment
      were important prognostic factors.

PMID- 24901178
TI  - A modified overlap method using a linear stapler for intracorporeal
      esophagojejunostomy after laparoscopic total gastrectomy.
AB  - BACKGROUND/AIMS: Intracorporeal esophagojejunostomy represents the most difficult
      step during laparoscopic total gastrectomy (LTG). A novel technique for
      intracorporeal esophagojejunostomy was recently developed and named the "overlap
      method." However, this procedure is thought to have some technical disadvantages.
      To facilitate intracorporeal esophagojejunostomy, we developed some modifications
      for the overlap method. METHODOLOGY: From October 2009 to July 2013, 63
      consecutive patients with gastric cancer underwent LTG at our institution. Our
      modified overlap method was used for 54 patients with the following
      modifications. First, the esophagus was transected while being rotated by
      approximately 90 degrees in the clockwise direction. Second, an endoscopic linear
      stapler was used through the right lower trocar to create a side-to-side
      esophagojejunostomy. Third, the entry hole of the linear stapler was closed with
      intracorporeal hand-sewn continuous suturing. This procedure was termed the
      "modified overlap method." RESULTS: In 53 patients with the exception of one
      case, the modified overlap method was successfully completed (98.1%). Only one
      patient developed esophagojejunal anastomotic leakage (1.9%), which recovered
      well with conservative management. No postoperative anastomotic stricture or
      bleeding occurred. CONCLUSIONS: Our modified overlap method for intracorporeal
      esophagojejunostomy provides amazingly satisfactory outcomes. We believe this
      procedure could become a standard method for intracorporeal esophagojejunostomy
      after LTG.

PMID- 24901205
TI  - Perspectives of nanoemulsion assisted oral delivery of docetaxel for improved
      chemotherapy of cancer.
AB  - CONTEXT: Nanoemulsions (NE) are one of the robust delivery tools for drugs due to
      their higher stability and efficacy. OBJECTIVES: The purpose of present
      investigation is to develop stable, effective and safe NE of docetaxel (DTX).
      METHODS: Soybean oil, lecithin, Pluronic F68, PEG 4000 and ethanol were employed
      as excipients and NEs were prepared by hot homogenization followed by ultra
      sonication. NEs were optimized and investigated for different in vitro and in
      vivo parameters viz. droplet size, poly dispersity index, charge; zeta potential,
      drug content and in vitro drug release, in vitro cytotoxicity, in vitro cell
      uptake and acute toxicity. Transmission electron microscopy was performed to
      study morphology and structure of NEs. Stability studies of the optimized
      formulation were performed. RESULTS: Droplet size, poly dispersity index, zeta
      potential, drug content and in vitro drug release were found to be 233.23 +/- 4.3
      nm, 0.24 +/- 0.010, -43.66 +/- 1.9 mV, 96.76 +/- 1.5%, 96.25 +/- 2.1%,
      respectively. NE F11 exhibited higher cell uptake (2.83 times than control) and
      strong cytotoxic activity against MCF-7 cancer cells (IC50; 13.55 +/- 0.21 ug/mL
      at 72 h) whereas no toxicity or necrosis was observed with liver and kidney
      tissues of mice at a dose of 20 mg/kg. Transmission electron microscopy ensured
      formation of poly-dispersed and spherical droplets in nanometer range. NE F11
      (values indicated above) was selected as the optimized formulation based on the
      aforesaid parameters. CONCLUSION: Conclusively, stable, effective and safe NE was
      developed which might be used as an alternative DTX therapy.

PMID- 24901206
TI  - Formulation development of a novel targeted theranostic nanoemulsion of docetaxel
      to overcome multidrug resistance in ovarian cancer.
AB  - OBJECTIVE: Ovarian cancer is a highly lethal disease in which the majority of
      patients eventually demonstrate multidrug resistance. Develop a novel active
      targeted theranostic nanomedicine designed to overcome drug efflux mechanisms,
      using a Generally Regarded As Safe (GRAS) grade nanoemulsion (NE) as a clinically
      relevant platform. MATERIALS AND METHODS: The NEs surface-functionalized with
      folate and gadolinium, were made using GRAS grade excipients and a high-shear
      microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3
      and SKOV3TR. The NE accumulation in tumors was evaluated in SKOV3 tumor-bearing
      mice by magnetic resonance imaging (MRI). RESULTS AND DISCUSSION: The NE with
      particle size < 150 nm were stable in plasma and parenteral fluids for 24 h.
      Ovarian cancer cells in vitro efficiently took up the non-targeted and folate
      targeted NEs; improved cytotoxicity was observed for the folate-targeted NEs
      showing a 270-fold drop in the IC50 in SKOV3TR cells as compared to docetaxel
      alone. The addition of gadolinium did not affect cell viability in vitro, but
      showed relaxation times comparable to Magnevist(r). Folate-targeted NEs
      accumulated in tumors for prolonged period of time compared to Magnevist(r) and
      showed enhanced contrast compared to non-targeted NEs with MRI in SKOV3 tumor
      bearing mice suggesting active targeting of NEs due to folate modification.
      CONCLUSIONS: A folate-targeted, theranostic NE delivers docetaxel by receptor
      mediated endocytosis that shows enhanced cytotoxicity capable of overcoming ABC
      transporter mediated taxane resistance. The diagnostic capability of the targeted
      nanomedicine showed enhanced contrast in tumors compared to clinically relevant
      MRI contrast agent Magnevist(r).

PMID- 24901207
TI  - Nasal-nanotechnology: revolution for efficient therapeutics delivery.
AB  - CONTEXT: In recent years, nanotechnology-based delivery systems have gained
      interest to overcome the problems of restricted absorption of therapeutic agents
      from the nasal cavity, depending upon the physicochemical properties of the drug
      and physiological properties of the human nose. OBJECTIVE: The well-tolerated and
      non-invasive nasal drug delivery when combined with the nanotechnology-based
      novel formulations and carriers, opens the way for the effective systemic and
      brain targeting delivery of various therapeutic agents. To accomplish competent
      drug delivery, it is imperative to recognize the interactions among the
      nanomaterials and the nasal biological environment, targeting cell-surface
      receptors, drug release, multiple drug administration, stability of therapeutic
      agents and molecular mechanisms of cell signaling involved in patho-biology of
      the disease under consideration. METHODS: Quite a few systems have been
      successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon
      nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based
      nanosystems have also been studied in vitro and in vivo for the delivery of
      several therapeutic agents which shown promising concentrations in the brain
      after nasal administration. RESULTS AND CONCLUSION: The use of nanomaterials
      including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via
      nasal route is a new approach to control the disease progression. In this review,
      the recent developments in nanotechnology utilized for nasal drug delivery have
      been discussed.

PMID- 24901208
TI  - Insulin-loaded alginic acid nanoparticles for sublingual delivery.
AB  - Alginic acid nanoparticles (NPs) containing insulin, with nicotinamide as
      permeation enhancer were developed for sublingual delivery. The lower
      concentration of proteolytic enzymes, lower thickness and enhanced retention due
      to bioadhesive property, were relied on for enhanced insulin absorption. Insulin
      loaded NPs were prepared by mild and aqueous based nanoprecipitation process. NPs
      were negatively charged and had a mean size of ~200 nm with low dispersity index.
      Insulin loading capacities of >95% suggested a high association of insulin with
      alginic acid. Fourier Transform Infra-Red Spectroscopy (FTIR) spectra and DSC
      (Differential Scanning Calorimetry) thermogram of insulin-loaded NPs revealed the
      association of insulin with alginic acid. Circular dichroism (CD) spectra
      confirmed conformational stability, while HPLC analysis confirmed chemical
      stability of insulin in the NPs. Sublingually delivered NPs with nicotinamide
      exhibited high pharmacological availability (>100%) and bioavailability (>80%) at
      a dose of 5 IU/kg. The high absolute pharmacological availability of 20.2% and
      bioavailability of 24.1% in comparison with subcutaneous injection at 1 IU/kg, in
      the streptozotocin-induced diabetic rat model, suggest the insulin-loaded alginic
      acid NPs as a promising sublingual delivery system of insulin. 

PMID- 24901209
TI  - Immunosafety and chronic toxicity evaluation of monomethoxypoly(ethylene glycol)
      b-poly(lactic acid) polymer micelles for paclitaxel delivery.
AB  - To investigate the physicochemical properties, immunosafety and chronic toxicity
      of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer
      used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance
      (H-NMR), dynamic light scattering and fluorescence probe technique were conducted
      to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded
      polymeric micelles were characterized regarding their particle size, entrapment
      efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The
      complement activation in human serum and mast cells degranulation were performed
      by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study
      was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60)
      micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w.
      Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60)
      micelles have spherical shape with dense core. In vitro release study showed a
      sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA
      (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60)
      showed a lower complement activation ability compared to mPEG-PLA (50/50) and
      CremophorA(r) EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG
      PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and
      Cr EL. 

PMID- 24901210
TI  - Beta-alanine supplementation improves jumping power and affects severe-intensity
      performance in professional alpine skiers.
AB  - INTRODUCTION: Supplementation with beta-alanine may have positive effects on
      severe-intensity, intermittent, and isometric strength-endurance performance.
      These could be advantageous for competitive alpine skiers, whose races last 45 to
      150 s, require metabolic power above the aerobic maximum, and involve isometric
      muscle work. Further, beta-alanine supplementation affects the muscle force
      frequency relationship, which could influence explosiveness. We explored the
      effects of beta-alanine on explosive jump performance, severe exercise energy
      metabolism, and severe-intensity ski-like performance. METHODS: Nine male elite
      alpine skiers consumed 4.8 g/d beta-alanine or placebo for 5 weeks in a double
      blind fashion. Before and after, they performed countermovement jumps (CMJ), a 90
      s cycling bout at 110% VO2max (CLT), and a maximal 90-s box jump test (BJ90).
      RESULTS: Beta-alanine improved maximal (+7 +/- 3%, d = 0.9) and mean CMJ power
      (+7 +/- 2%, d = 0.7), tended to reduce oxygen deficit (-3 +/- 8%, p = .06) and
      lactate accumulation (-12 +/- 31%) and enhance aerobic energy contribution (+1.3
      +/- 2.9%, p = .07) in the CLT, and improved performance in the last third of BJ90
      (+7 +/- 4%, p = .02). These effects were not observed with placebo. CONCLUSIONS:
      Beta-alanine supplementation improved explosive and repeated jump performance in
      elite alpine skiers. Enhanced muscle contractility could possibly explain
      improved explosive and repeated jump performance. Increased aerobic energy
      production could possibly help explain repeated jump performance as well.

PMID- 24901211
TI  - The microbiota and helminths: sharing the same niche in the human host.
AB  - Human gastrointestinal bacteria often share their environment with parasitic
      worms, allowing physical and physiological interaction between the two groups.
      Such associations have the potential to affect host health as well as the
      bacterial and helminth populations. Although still in its early stages, research
      on the interaction between the microbiome and parasitic helminths in humans
      offers the potential to improve health by manipulating the microbiome.
      Previously, supplementation with various nutritional compounds has been found to
      increase the abundance of potentially beneficial gut commensal bacteria. Thus,
      nutritional microbiome manipulation to produce an environment which may decrease
      malnutrition associated with helminth infection and/or aid host recovery from
      disease is conceivable. This review discusses the influence of the gut microbiota
      and helminths on host nutrition and immunity and the subsequent effects on the
      human host's overall health. It also discusses changes occurring in the
      microbiota upon helminth infections and the underlying mechanisms leading to
      these changes. There are still significant knowledge gaps which need to be filled
      before meaningful progress can be made in translating knowledge from studying the
      human gut microbiome into therapeutic strategies. Ultimately this review aims to
      discuss our current knowledge as well as highlight areas requiring further
      investigation.

PMID- 24901213
TI  - Atmospheric oxidation mechanism of toluene.
AB  - The atmospheric oxidation mechanism of toluene initiated by OH radical addition
      is investigated by quantum chemistry calculations at M06-2X, G3MP2-RAD, and ROCBS
      QB3 levels and by kinetics calculation by using transition state theory and
      unimolecular reaction theory coupled with master equation (RRKM-ME). The
      predicted branching ratios are 0.15, 0.59, 0.05, and 0.14 for OH additions to
      ipso, ortho, meta, and para positions (forming R1-R4 adducts), respectively. The
      fate of R2, R4, and R1 is investigated in detail. In the atmosphere, R2 reacts
      with O2 either by irreversible H-abstraction to form o-cresol (36%), or by
      reversible recombination to R2-1OO-syn and R2-3OO-syn, which subsequently cyclize
      to bicyclic radical R2-13OO-syn (64%). Similarly, R4 reacts with O2 with
      branching ratios of 61% for p-cresol and 39% for R4-35OO-syn, while reaction of
      R1 and O2 leads to R1-26OO-syn. RRKM-ME calculations show that the reactions of
      R2/R4 with O2 have reached their high-pressure limits at 760 Torr and the
      formation of R2-16O-3O-s is only important at low pressure, i.e., 5.4% at 100
      Torr. The bicyclic radicals (R2-13OO-syn, R4-35OO-syn, and R1-26OO-syn) will
      recombine with O2 to produce bicyclic alkoxy radicals after reacting with NO. The
      bicyclic alkoxy radicals would break the ring to form products
      methylglyoxal/glyoxal (MGLY/GLY) and their corresponding coproducts
      butenedial/methyl-substituted butenedial as proposed in earlier studies. However,
      a new reaction pathway is found for the bicyclic alkoxy radicals, leading to
      products MGLY/GLY and 2,3-epoxybutandial/2-methyl-2,3-epoxybutandial. A new
      mechanism is proposed for the atmospheric oxidation mechanism of toluene based on
      current theoretical and previous theoretical and experimental results. The new
      mechanism predicts much lower yield of GLY and much higher yield of butenedial
      than other atmospheric models and recent experimental measurements. The new
      mechanism calls for detection of proposed products 2,3-epoxybutandial and 2
      methyl-2,3-epoxybutandial. 

PMID- 24901212
TI  - Phytochemicals perturb membranes and promiscuously alter protein function.
AB  - A wide variety of phytochemicals are consumed for their perceived health
      benefits. Many of these phytochemicals have been found to alter numerous cell
      functions, but the mechanisms underlying their biological activity tend to be
      poorly understood. Phenolic phytochemicals are particularly promiscuous modifiers
      of membrane protein function, suggesting that some of their actions may be due to
      a common, membrane bilayer-mediated mechanism. To test whether bilayer
      perturbation may underlie this diversity of actions, we examined five bioactive
      phenols reported to have medicinal value: capsaicin from chili peppers, curcumin
      from turmeric, EGCG from green tea, genistein from soybeans, and resveratrol from
      grapes. We find that each of these widely consumed phytochemicals alters lipid
      bilayer properties and the function of diverse membrane proteins. Molecular
      dynamics simulations show that these phytochemicals modify bilayer properties by
      localizing to the bilayer/solution interface. Bilayer-modifying propensity was
      verified using a gramicidin-based assay, and indiscriminate modulation of
      membrane protein function was demonstrated using four proteins: membrane-anchored
      metalloproteases, mechanosensitive ion channels, and voltage-dependent potassium
      and sodium channels. Each protein exhibited similar responses to multiple
      phytochemicals, consistent with a common, bilayer-mediated mechanism. Our results
      suggest that many effects of amphiphilic phytochemicals are due to cell membrane
      perturbations, rather than specific protein binding. 

PMID- 24901214
TI  - Experience of the first breastfeeding session in association with the use of the
      hands-on approach by healthcare professionals: a population-based Swedish study.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of healthcare
      professionals' use of the hands-on approach during the first breastfeeding
      session postpartum and its possible association with the mothers' experience of
      their first breastfeeding session. MATERIALS AND METHODS: This was a population
      based longitudinal study conducted at Uppsala University Hospital, Uppsala,
      Sweden, of all women giving birth at the hospital from May 2006 to June 2007. Six
      months postpartum, a questionnaire including questions regarding breastfeeding
      support, caregiving routines, depressive symptoms, and the woman's experience of
      the first breastfeeding session was sent to the mothers. The main outcome
      measures were use of the hands-on approach during the first breastfeeding session
      and the mother's experience of the breastfeeding session. RESULTS: In total, 879
      women participated in the study. Thirty-eight percent of the women received the
      hands-on approach during the first breastfeeding session. High body mass index,
      primiparity, and having the first breastfeeding session postponed were all
      independently associated with the hands-on approach. Women who received the hands
      on approach were more likely to report a negative experience of the first
      breastfeeding session (odds ratio=4.48; 95% confidence interval, 2.57-7.82), even
      after adjustment for possible confounders (odds ratio=2.37; 95% confidence
      interval, 1.02-5.50). CONCLUSIONS: This study indicates that the hands-on
      approach is commonly used during the first breastfeeding session and is
      associated with a more negative experience of the first breastfeeding session.
      Consequently, caregivers need to question the use of this method, and further
      research about breastfeeding support is required.

PMID- 24901215
TI  - Effects of internalized gold nanoparticles with respect to cytotoxicity and
      invasion activity in lung cancer cells.
AB  - The effect of gold nanoparticles on lung cancer cells is not yet clear. In this
      study, we investigated the cytotoxicity and cell invasion activity of lung cancer
      cells after treatment with gold nanoparticles and showed that small gold
      nanoparticles can be endocytosed by lung cancer cells and that they facilitate
      cell invasion. The growth of A549 cells was inhibited after treatment with 5-nm
      gold nanoparticles, but cell invasion increased. Endocytosed gold nanoparticles
      (size, 10 nm) notably promoted the invasion activity of 95D cells. All these
      effects of gold nanoparticles were not seen after treatment with larger particles
      (20 and 40 nm). The enhanced invasion activity may be associated with the
      increased expression of matrix metalloproteinase 9 and intercellular adhesion
      molecule-1. In this study, we obtained evidence for the effect of gold
      nanoparticles on lung cancer cell invasion activity in vitro. Moreover, matrix
      metalloproteinase 9 and intercellular adhesion molecule-1, key modulators of cell
      invasion, were found to be regulated by gold nanoparticles. These data also
      demonstrate that the responses of the A549 and 95D cells to gold nanoparticles
      have a remarkable relationship with their unique size-dependent physiochemical
      properties. Therefore, this study provides a new perspective for cell biology
      research in nanomedicine. 

PMID- 24901217
TI  - Asymmetric synthesis of alpha-branched amines via Rh(III)-catalyzed C-H bond
      functionalization.
AB  - The first asymmetric intermolecular addition of non-acidic C-H bonds to imines is
      reported. The use of the activating N-perfluorobutanesulfinyl imine substituent
      is essential for achieving sufficient reactivity and provides outstanding
      diastereoselectivity (>98:2 dr). Straightforward removal of the sulfinyl group
      with HCl yields the highly enantiomerically enriched amine hydrochlorides. 

PMID- 24901216
TI  - Exopolysaccharide (EPS) synthesis by Oenococcus oeni: from genes to phenotypes.
AB  - Oenococcus oeni is the bacterial species which drives malolactic fermentation in
      wine. The analysis of 50 genomic sequences of O. oeni (14 already available and
      36 newly sequenced ones) provided an inventory of the genes potentially involved
      in exopolysaccharide (EPS) biosynthesis. The loci identified are: two gene
      clusters named eps1 and eps2, three isolated glycoside-hydrolase genes named
      dsrO, dsrV and levO, and three isolated glycosyltransferase genes named gtf, it3,
      it4. The isolated genes were present or absent depending on the strain and the
      eps gene clusters composition diverged from one strain to another. The soluble
      and capsular EPS production capacity of several strains was examined after growth
      in different culture media and the EPS structure was determined. Genotype to
      phenotype correlations showed that several EPS biosynthetic pathways were active
      and complementary in O. oeni. Can be distinguished: (i) a Wzy-dependent synthetic
      pathway, allowing the production of heteropolysaccharides made of glucose,
      galactose and rhamnose, mainly in a capsular form, (ii) a glucan synthase pathway
      (Gtf), involved in beta-glucan synthesis in a free and a cell-associated form,
      giving a ropy phenotype to growth media and (iii) homopolysaccharide synthesis
      from sucrose (alpha-glucan or beta-fructan) by glycoside-hydrolases of the GH70
      and GH68 families. The eps gene distribution on the phylogenetic tree was
      examined. Fifty out of 50 studied genomes possessed several genes dedicated to
      EPS metabolism. This suggests that these polymers are important for the
      adaptation of O. oeni to its specific ecological niche, wine and possibly
      contribute to the technological performance of malolactic starters.

PMID- 24901218
TI  - Gene expression profiling analysis of bisphenol A-induced perturbation in
      biological processes in ER-negative HEK293 cells.
AB  - Bisphenol A (BPA) is an environmental endocrine disruptor which has been detected
      in human bodies. Many studies have implied that BPA exposure is harmful to human
      health. Previous studies mainly focused on BPA effects on estrogen receptor (ER)
      positive cells. Genome-wide impacts of BPA on gene expression in ER-negative
      cells is unclear. In this study, we performed RNA-seq to characterize BPA-induced
      cellular and molecular impacts on ER-negative HEK293 cells. The microscopic
      observation showed that low-dose BPA exposure did not affect cell viability and
      morphology. Gene expression profiling analysis identified a list of
      differentially expressed genes in response to BPA exposure in HEK293 cells. These
      genes were involved in variable important biological processes including ion
      transport, cysteine metabolic process, apoptosis, DNA damage repair, etc.
      Notably, BPA up-regulated the expression of ERCC5 encoding a DNA endonuclease for
      nucleotide-excision repair. Further electrochemical experiment showed that BPA
      induced significant DNA damage in ER-positive MCF-7 cells but not in ER-negative
      HEK293 cells. Collectively, our study revealed that ER-negative HEK293 cells
      employed mechanisms in response to BPA exposure different from ER-positive cells.

PMID- 24901220
TI  - A quantum chemical topological analysis of the C-C bond formation in organic
      reactions involving cationic species.
AB  - ELF topological analysis of the ionic Diels-Alder (I-DA) reaction between the N,N
      dimethyliminium cation and cyclopentadiene (Cp) has been performed in order to
      characterise the C-C single bond formation. The C-C bond formation begins in the
      short range of 2.00-1.96 Avia a C-to-C pseudoradical coupling between the most
      electrophilic center of the iminium cation and one of the two most nucleophilic
      centers of Cp. The electron density of the pseudoradical center generated at the
      most electrophilic carbon of the iminium cation comes mainly from the global
      charge transfer which takes place along the reaction. Analysis of the global
      reactivity indices indicates that the very high electrophilic character of the
      iminium cation is responsible for the negative activation energy found in the gas
      phase. On the other hand, the analysis of the radical P(k)(o) Parr functions of
      the iminium cation, and the nucleophilic P(k)(-) Parr functions of Cp makes the
      characterisation of the most favourable two-center interaction along the
      formation of the C-C single bond possible.

PMID- 24901219
TI  - Proteomic analysis of adult Ascaris suum fluid compartments and secretory
      products.
AB  - BACKGROUND: Strategies employed by parasites to establish infections are poorly
      understood. The host-parasite interface is maintained through a molecular dialog
      that, among other roles, protects parasites from host immune responses. Parasite
      excretory/secretory products (ESP) play major roles in this process.
      Understanding the biology of protein secretion by parasites and their associated
      functional processes will enhance our understanding of the roles of ESP in host
      parasite interactions. METHODOLOGY/PRINCIPAL FINDINGS: ESP was collected after
      culturing 10 adult female Ascaris suum. Perienteric fluid (PE) and uterine fluid
      (UF) were collected directly from adult females by dissection. Using SDS-PAGE
      coupled with LC-MS/MS, we identified 175, 308 and 274 proteins in ESP, PE and UF,
      respectively. Although many proteins were shared among the samples, the protein
      composition of ESP was distinct from PE and UF, whereas PE and UF were highly
      similar. The distribution of gene ontology (GO) terms for proteins in ESP, PE and
      UF supports this claim. Comparison of ESP composition in A. suum, Brugia malayi
      and Heligmosoides polygyrus showed that proteins found in UF were also secreted
      by males and by larval stages of other species, suggesting that multiple routes
      of secretion may be used for homologous proteins. ESP composition of nematodes is
      both phylogeny- and niche-dependent. CONCLUSIONS/SIGNIFICANCE: Analysis of the
      protein composition of A. suum ESP and UF leads to the conclusion that the
      excretory-secretory apparatus and uterus are separate routes for protein release.
      Proteins detected in ESP have distinct patterns of biological functions compared
      to those in UF. PE is likely to serve as the source of the majority of proteins
      in UF. This analysis expands our knowledge of the biology of protein secretion
      from nematodes and will inform new studies on the function of secreted proteins
      in the orchestration of host-parasite interactions.

PMID- 24901221
TI  - PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila.
AB  - Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a
      protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been
      suggested to support mitochondrial quality control. We have reported that Parkin
      is phosphorylated at Ser65 within the ubiquitin-like domain by PINK1 in mammalian
      cultured cells. However, it remains unclear whether Parkin phosphorylation is
      involved in mitochondrial maintenance and activity of dopaminergic neurons in
      vivo. Here, we examined the effects of Parkin phosphorylation in Drosophila, in
      which the phosphorylation residue is conserved at Ser94. Morphological changes of
      mitochondria caused by the ectopic expression of wild-type Parkin in muscle
      tissue and brain dopaminergic neurons disappeared in the absence of PINK1. In
      contrast, phosphomimetic Parkin accelerated mitochondrial fragmentation or
      aggregation and the degradation of mitochondrial proteins regardless of PINK1
      activity, suggesting that the phosphorylation of Parkin boosts its ubiquitin
      ligase activity. A non-phosphorylated form of Parkin fully rescued the muscular
      mitochondrial degeneration due to the loss of PINK1 activity, whereas the
      introduction of the non-phosphorylated Parkin mutant in Parkin-null flies led to
      the emergence of abnormally fused mitochondria in the muscle tissue. Manipulating
      the Parkin phosphorylation status affected spontaneous dopamine release in the
      nerve terminals of dopaminergic neurons, the survivability of dopaminergic
      neurons and flight activity. Our data reveal that Parkin phosphorylation
      regulates not only mitochondrial function but also the neuronal activity of
      dopaminergic neurons in vivo, suggesting that the appropriate regulation of
      Parkin phosphorylation is important for muscular and dopaminergic functions. 

PMID- 24901224
TI  - Nonspecific genitourinary pain improves after prostatectomy using holmium laser
      enucleation of prostate in patients with benign prostatic hyperplasia: a
      prospective study.
AB  - OBJECTIVE: To investigate changes in nonspecific genitourinary discomfort or pain
      (GUDP) before and after holmium laser enucleation of prostate (HoLEP). GUDP
      associated with lower urinary tract symptoms (LUTS) is a common complaint among
      benign prostatic hyperplasia (BPH) patients, but very little is known about this
      clinical entity. METHODS: From February 2010 to August 2011, 100 HoLEP patients
      with complete clinical data at a single institution were enrolled in the study to
      analyze the degree of GUDP with a visual analog scale (VAS) from 0 to 10 points
      at baseline and at 3 and 6 months postoperatively, and to investigate any
      relationships between GUDP and urodynamics, uroflowmetry, and scores from the
      International Prostate Symptom Score (IPSS) questionnaire. RESULTS: Fifty-six
      patients had LUTS only, while the remaining 44 had both LUTS and GUDP. Pain was
      located in the suprapubic (42.0%), perineal/penile (33.0%), back (17.0%), and
      perianal (8.0%) regions. During the post-operative period, at six months, the
      VAS, IPSS, peak flow rate and post-void residual volume had improved
      significantly in 44 GUDP patients (p<0.010). GUDP had completely resolved in 40
      (90.9%) patients and had decreased in four (9.1%) patients, while seven (12.5%)
      patients developed GUDP with voiding in the urethral and perineal areas by the
      third month postoperatively. When compared to patients with complete resolution,
      those with persistent GUDP were found to have a significantly higher preoperative
      presence of bladder outlet obstruction (BOO) as an independent risk factor (OR
      6.173, 95% CI 1.132-1.323). CONCLUSION: Both GUDP and LUTS improved significantly
      after HoLEP. Patients with significant preoperative BOO tended to have persistent
      GUDP after surgery.

PMID- 24901222
TI  - A loss of function analysis of host factors influencing Vaccinia virus
      replication by RNA interference.
AB  - Vaccinia virus (VACV) is a large, cytoplasmic, double-stranded DNA virus that
      requires complex interactions with host proteins in order to replicate. To
      explore these interactions a functional high throughput small interfering RNA
      (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify
      host factors (HF) influencing the replication and spread of an eGFP-tagged VACV.
      The experimental design incorporated a low multiplicity of infection, thereby
      enhancing detection of cellular proteins involved in cell-to-cell spread of VACV.
      The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV
      replication. These HFs were investigated further by comparisons with
      transcriptional profiling data sets and HFs identified in RNAi screens of other
      viruses. In addition, functional and pathway analysis of the entire screen was
      carried out to highlight cellular mechanisms involved in VACV replication. This
      revealed, as anticipated, that many pro-viral HFs are involved in translation of
      mRNA and, unexpectedly, suggested that a range of proteins involved in cellular
      transcriptional processes and several DNA repair pathways possess anti-viral
      activity. Multiple components of the AMPK complex were found to act as pro-viral
      HFs, while several septins, a group of highly conserved GTP binding proteins with
      a role in sequestering intracellular bacteria, were identified as strong anti
      viral VACV HFs. This screen has identified novel and previously unexplored roles
      for cellular factors in poxvirus replication. This advancement in our
      understanding of the VACV life cycle provides a reliable knowledge base for the
      improvement of poxvirus-based vaccine vectors and development of anti-viral
      theraputics. 

PMID- 24901223
TI  - Coiled-coil proteins facilitated the functional expansion of the centrosome.
AB  - Repurposing existing proteins for new cellular functions is recognized as a main
      mechanism of evolutionary innovation, but its role in organelle evolution is
      unclear. Here, we explore the mechanisms that led to the evolution of the
      centrosome, an ancestral eukaryotic organelle that expanded its functional
      repertoire through the course of evolution. We developed a refined sequence
      alignment technique that is more sensitive to coiled coil proteins, which are
      abundant in the centrosome. For proteins with high coiled-coil content, our
      algorithm identified 17% more reciprocal best hits than BLAST. Analyzing 108
      eukaryotic genomes, we traced the evolutionary history of centrosome proteins. In
      order to assess how these proteins formed the centrosome and adopted new
      functions, we computationally emulated evolution by iteratively removing the most
      recently evolved proteins from the centrosomal protein interaction network.
      Coiled-coil proteins that first appeared in the animal-fungi ancestor act as
      scaffolds and recruit ancestral eukaryotic proteins such as kinases and
      phosphatases to the centrosome. This process created a signaling hub that is
      crucial for multicellular development. Our results demonstrate how ancient
      proteins can be co-opted to different cellular localizations, thereby becoming
      involved in novel functions. 

PMID- 24901225
TI  - Mutation of serine 1333 in the ATR HEAT repeats creates a hyperactive kinase.
AB  - Subcellular localization, protein interactions, and post-translational
      modifications regulate the DNA damage response kinases ATR, ATM, and DNA-PK.
      During an analysis of putative ATR phosphorylation sites, we found that a single
      mutation at S1333 creates a hyperactive kinase. In vitro and in cells, mutation
      of S1333 to alanine (S1333A-ATR) causes elevated levels of kinase activity with
      and without the addition of the protein activator TOPBP1. S1333 mutations to
      glycine, arginine, or lysine also create a hyperactive kinase, while mutation to
      aspartic acid decreases ATR activity. S1333A-ATR maintains the G2 checkpoint and
      promotes completion of DNA replication after transient exposure to replication
      stress but the less active kinase, S1333D-ATR, has modest defects in both of
      these functions. While we find no evidence that S1333 is phosphorylated in
      cultured cells, our data indicate that small changes in the HEAT repeats can have
      large effects on kinase activity. These mutants may serve as useful tools for
      future studies of the ATR pathway. 

PMID- 24901226
TI  - Identifying and addressing barriers to uptake of voluntary medical male
      circumcision in Nyanza, Kenya among men 18-35: a qualitative study.
AB  - BACKGROUND: Uptake of VMMC among adult men has been lower than desired in Nyanza,
      Kenya. Previous research has identified several barriers to uptake but
      qualitative exploration of barriers is limited and evidence-informed
      interventions have not been fully developed. This study was conducted in 2012 to
      1) increase understanding of barriers to VMMC and 2) to inform VMMC rollout
      through the identification of evidence-informed interventions among adult men at
      high risk of HIV in Nyanza Province, Kenya. METHODS: Focus groups (n = 8) and
      interviews were conducted with circumcised (n = 8) and uncircumcised men (n = 14)
      from the two districts in Nyanza, Kenya. Additional interviews were conducted
      with female partners (n = 20), health providers (n = 12), community leaders (n =
      12) and employers (n = 12). Interview and focus group guides included questions
      about individual, interpersonal and societal barriers to VMMC uptake and ways to
      overcome them. Inductive thematic coding and analysis were conducted through a
      standard iterative process. RESULTS: Two primary concerns with VMMC emerged 1)
      financial issues including missing work, losing income during the procedure and
      healing and family survival during the recovery period and 2) fear of pain during
      and after the procedure. Key interventions to address financial concerns
      included: a food or cash transfer, education on saving and employer-based
      benefits. Interventions to address concerns about pain included refining the
      content of demand creation and counseling messages about pain and improving the
      ways these messages are delivered. CONCLUSIONS: Men need accurate and detailed
      information on what to expect during and after VMMC regarding both pain and time
      away from work. This information should be incorporated into demand creation
      activities for men considering circumcision. Media content should frankly and
      correctly address these concerns. Study findings support scale up and/or further
      improvement of these ongoing educational programs and specifically targeting the
      demand creation period.

PMID- 24901227
TI  - Proteomic analysis of Mecistocirrus digitatus and Haemonchus contortus intestinal
      protein extracts and subsequent efficacy testing in a vaccine trial.
AB  - BACKGROUND: Gastrointestinal nematode infections, such as Haemonchus contortus
      and Mecistocirrus digitatus, are ranked in the top twenty diseases affecting
      small-holder farmers' livestock, yet research into M. digitatus, which infects
      cattle and buffalo in Asia is limited. Intestine-derived native protein vaccines
      are effective against Haemonchus, yet the protective efficacy of intestine
      derived M. digitatus proteins has yet to be determined. METHODOLOGY/PRINCIPAL
      FINDINGS: A simplified protein extraction protocol (A) is described and compared
      to an established method (B) for protein extraction from H. contortus. Proteomic
      analysis of the H. contortus and M. digitatus protein extracts identified
      putative vaccine antigens including aminopeptidases (H11), zinc
      metallopeptidases, glutamate dehydrogenase, and apical gut membrane polyproteins.
      A vaccine trial compared the ability of the M. digitatus extract and two
      different H. contortus extracts to protect sheep against H. contortus challenge.
      Both Haemonchus fractions (A and B) were highly effective, reducing cumulative
      Faecal Egg Counts (FEC) by 99.19% and 99.89% and total worm burdens by 87.28% and
      93.64% respectively, compared to the unvaccinated controls. There was no effect
      on H. contortus worm burdens following vaccination with the M. digitatus extract
      and the 28.2% reduction in cumulative FEC was not statistically significant.
      However, FEC were consistently lower in the M. digitatus extract vaccinates
      compared to the un-vaccinated controls from 25 days post-infection.
      CONCLUSIONS/SIGNIFICANCE: Similar, antigenically cross-reactive proteins are
      found in H. contortus and M. digitatus; this is the first step towards developing
      a multivalent native vaccine against Haemonchus species and M. digitatus. The
      simplified protein extraction method could form the basis for a locally produced
      vaccine against H. contortus and, possibly M. digitatus, in regions where
      effective cold chains for vaccine distribution are limited. The application of
      such a vaccine in these regions would reduce the need for anthelmintic treatment
      and the resultant selection for anthelmintic resistant parasites.

PMID- 24901228
TI  - Targeting Echinococcus multilocularis stem cells by inhibition of the Polo-like
      kinase EmPlk1.
AB  - BACKGROUND: Alveolar echinococcosis (AE) is a life-threatening disease caused by
      larvae of the fox-tapeworm Echinococcus multilocularis. Crucial to AE pathology
      is continuous infiltrative growth of the parasite's metacestode stage, which is
      driven by a population of somatic stem cells, called germinative cells. Current
      anti-AE chemotherapy using benzimidazoles is ineffective in eliminating the
      germinative cell population, thus leading to remission of parasite growth upon
      therapy discontinuation. METHODOLOGY/PRINCIPAL FINDINGS: We herein describe the
      characterization of EmPlk1, encoded by the gene emplk1, which displays
      significant homologies to members of the Plk1 sub-family of Polo-like kinases
      that regulate mitosis in eukaryotic cells. We demonstrate germinative cell
      specific expression of emplk1 by RT-PCR, transcriptomics, and in situ
      hybridization. We also show that EmPlk1 can induce germinal vesicle breakdown
      when heterologously expressed in Xenopus oocytes, indicating that it is an active
      kinase. This activity was significantly suppressed in presence of BI 2536, a Plk1
      inhibitor that has been tested in clinical trials against cancer. Addition of BI
      2536 at concentrations as low as 20 nM significantly blocked the formation of
      metacestode vesicles from cultivated Echinococcus germinative cells. Furthermore,
      low concentrations of BI 2536 eliminated the germinative cell population from
      mature metacestode vesicles in vitro, yielding parasite tissue that was no longer
      capable of proliferation. CONCLUSIONS/SIGNIFICANCE: We conclude that BI 2536
      effectively inactivates E. multilocularis germinative cells in parasite larvae in
      vitro by direct inhibition of EmPlk1, thus inducing mitotic arrest and
      germinative cell killing. Since germinative cells are decisive for parasite
      proliferation and metastasis formation within the host, BI 2536 and related
      compounds are very promising compounds to complement benzimidazoles in AE
      chemotherapy.

PMID- 24901229
TI  - Identification of aurora kinase A as an unfavorable prognostic factor and
      potential treatment target for metastatic gastrointestinal stromal tumors.
AB  - Although imatinib mesylate (IM) has revolutionized the management of
      gastrointestinal stromal tumors (GISTs), drug resistance remains a challenge.
      Previous studies have shown that the expression of aurora kinase A (AURKA)
      predicts recurrence in patients with primary, surgically resected GISTs. The
      current study aimed to evaluate the significance of AURKA expression as an
      unfavorable prognostic marker for advanced GISTs, and provide evidence that AURKA
      could be a potential therapeutic target in GISTs. The prognostic significance of
      the expression of AURKA, along with other clinicopathological factors, was
      analyzed in a cohort of 99 IM-treated patients with advanced GISTs. The potential
      use of an inhibitor of AURKA as a therapeutic agent against GISTs was also tested
      in GIST cell lines. Among 99 enrolled patients, poor performance status, large
      tumor size, drug response, and AURKA overexpression were independent prognostic
      factors for poor progression-free survival (PFS). For overall survival (OS), only
      large tumor size and AURKA overexpression were identified as independent
      unfavorable factors. In an in vitro study, MLN8237, an AURKA inhibitor, inhibited
      growth of both IM-sensitive and IM-resistant GIST cells in a concentration
      dependent manner, and exhibited synergistic cytotoxicity with IM in GIST cells.
      The inhibitory effect of MLN8237 in GIST cells could be attributed to the
      induction of G2/M arrest, apoptosis, and senescence. Our study shows that AURKA
      expression independently predicted poor PFS and OS in patients with advanced
      GISTs who were treated with IM. An AURKA inhibitor may have potential as a
      therapeutic agent for both IM-sensitive and IM-resistant GISTs. 

PMID- 24901230
TI  - From laboratory to field: OsNRAMP5-knockdown rice is a promising candidate for Cd
      phytoremediation in paddy fields.
AB  - Previously, we reported that OsNRAMP5 functions as a manganese, iron, and cadmium
      (Cd) transporter. The shoot Cd content in OsNRAMP5 RNAi plants was higher than
      that in wild-type (WT) plants, whereas the total Cd content (roots plus shoots)
      was lower. For efficient Cd phytoremediation, we produced OsNRAMP5 RNAi plants
      using the natural high Cd-accumulating cultivar Anjana Dhan (A5i). Using a
      positron-emitting tracer imaging system, we assessed the time-course of Cd
      absorption and accumulation in A5i plants. Enhanced 107Cd translocation from the
      roots to the shoots was observed in A5i plants. To evaluate the phytoremediation
      capability of A5i plants, we performed a field experiment in a Cd-contaminated
      paddy field. The biomass of the A5i plants was unchanged by the suppression of
      OsNRAMP5 expression; the A5i plants accumulated twice as much Cd in their shoots
      as WT plants. Thus, A5i plants could be used for rapid Cd extraction and the
      efficient phytoremediation of Cd from paddy fields, leading to safer food
      production. 

PMID- 24901232
TI  - 'Stratified Contraception': Emergency Contraceptive Pills and Women's
      Differential Experiences in Contemporary India.
AB  - Available without prescriptions in India since 2005, emergency contraceptive
      pills (ECPs) and their advertisements have provided women with increased
      contraceptive options and a vocabulary to talk about their reproductive lives. I
      draw on long-term fieldwork with women in urban India about ECPs, demonstrating a
      new form of 'stratified contraception' enabled by these pills and their
      advertisements. I posit that there are within India spaces that replicate the
      luxuries and privileges of the global North. These material conditions, I
      suggest, are replicated when it comes to contraception as there are hubs of women
      consumers of contraception and contraceptive advertising that participate in an
      'imagined cosmopolitanism' within the global South in close proximity to
      'contraceptive ghettos.' Moving beyond simplistic binaries, I outline three major
      stratifications along which women experience this medical technology and outline
      the implications for women and their contraceptive choices when notions of
      northern privilege exist in the 'South.' 

PMID- 24901231
TI  - A genetically-encoded YFP sensor with enhanced chloride sensitivity,
      photostability and reduced ph interference demonstrates augmented transmembrane
      chloride movement by gerbil prestin (SLC26a5).
AB  - BACKGROUND: Chloride is the major anion in cells, with many diseases arising from
      disordered Cl- regulation. For the non-invasive investigation of Cl- flux, YFP
      H148Q and its derivatives chameleon and Cl-Sensor previously were introduced as
      genetically encoded chloride indicators. Neither the Cl- sensitivity nor the pH
      susceptibility of these modifications to YFP is optimal for precise measurements
      of Cl- under physiological conditions. Furthermore, the relatively poor
      photostability of YFP derivatives hinders their application for dynamic and
      quantitative Cl- measurements. Dynamic and accurate measurement of physiological
      concentrations of chloride would significantly affect our ability to study
      effects of chloride on cellular events. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study, we developed a series of YFP derivatives to remove pH interference,
      increase photostability and enhance chloride sensitivity. The final product, EYFP
      F46L/Q69K/H148Q/I152L/V163S/S175G/S205V/A206K (monomeric Cl-YFP), has a chloride
      Kd of 14 mM and pKa of 5.9. The bleach time constant of 175 seconds is over 15
      fold greater than wild-type EYFP. We have used the sensor fused to the
      transmembrane protein prestin (gerbil prestin, SLC26a5), and shown for the first
      time physiological (mM) chloride flux in HEK cells expressing this protein. This
      modified fluorescent protein will facilitate investigations of dynamics of
      chloride ions and their mediation of cell function. CONCLUSIONS: Modifications to
      YFP (EYFP-F46L/Q69K/H148Q/I152L/V163S/S175G/S205V/A206K (monomeric Cl-YFP)
      results in a photostable fluorescent protein that allows measurement of
      physiological changes in chloride concentration while remaining minimally
      affected by changes in pH.

PMID- 24901233
TI  - Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.
AB  - Interleukin (IL)-1 signaling plays an important role in inflammatory processes,
      but also in malignant processes. The essential downstream event in IL-1 signaling
      is the activation of nuclear factor (NF)-kappaB, which leads to the expression of
      several genes that are involved in cell proliferation, invasion, angiogenesis and
      metastasis, among them VEGF-A. As microenvironment-derived IL-1beta is required
      for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we
      investigated IL-1beta-induced signal transduction and VEGF-A expression in C3842
      and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis
      assays and NF-kappaB-related gene expression analyses. Curcumin is a substance
      which inhibits IL-1 signaling very early by preventing the recruitment of IL-1
      receptor associated kinase (IRAK) to the IL-1 receptor. We demonstrate that IL-1
      signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells.
      We further show that Curcumin blocks IL-1beta-induced angiogenesis and NF-kappaB
      related gene expression. We suppose that IL-1 blockade is an additional treatment
      option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1
      blocking agents. 

PMID- 24901234
TI  - Shrinking wings for ultrasonic pitch production: hyperintense ultra-short
      wavelength calls in a new genus of neotropical katydids (Orthoptera:
      Tettigoniidae).
AB  - This article reports the discovery of a new genus and three species of predaceous
      katydid (Insecta: Orthoptera) from Colombia and Ecuador in which males produce
      the highest frequency ultrasonic calling songs so far recorded from an arthropod.
      Male katydids sing by rubbing their wings together to attract distant females.
      Their song frequencies usually range from audio (5 kHz) to low ultrasonic (30
      kHz). However, males of Supersonus spp. call females at 115 kHz, 125 kHz, and 150
      kHz. Exceeding the human hearing range (50 Hz-20 kHz) by an order of magnitude,
      these insects also emit their ultrasound at unusually elevated sound pressure
      levels (SPL). In all three species these calls exceed 110 dB SPL rms re 20 uPa
      (at 15 cm). Males of Supersonus spp. have unusually reduced forewings (<0.5
      mm(2)). Only the right wing radiates appreciable sound, the left bears the file
      and does not show a particular resonance. In contrast to most katydids, males of
      Supersonus spp. position and move their wings during sound production so that the
      concave aspect of the right wing, underlain by the insect dorsum, forms a
      contained cavity with sharp resonance. The observed high SPL at extreme carrier
      frequencies can be explained by wing anatomy, a resonant cavity with a membrane,
      and cuticle deformation.

PMID- 24901235
TI  - Nuclear CSPP1 expression defined subtypes of basal-like breast cancer.
AB  - BACKGROUND: The multi-exon CSPP1 gene, encoding for centrosome and microtubule
      associated proteins involved in ciliogenesis and cell division, is a candidate
      oncogene in luminal breast cancer but expression of CSPP1 proteins remained
      unexplored. METHODS: CSPP1 gene and protein expression was examined in normal
      mammary tissue, human breast cancer cell lines, and primary breast cancer
      biopsies from two patient cohorts. Cell type and epitope-dependent subcellular
      specific CSPP1 staining pattern in normal mammary gland epithelium and cancer
      biopsies were correlated to molecular and clinical parameters. RESULTS: A novel,
      nuclear localised CSPP1 isoform was exclusively detected in luminal epithelial
      cells, whereas cytoplasmic CSPP-L was generally expressed in normal mammary
      epithelium. Luminal cell-related nuclear CSPP1 expression was preserved in type
      matched cell lines and carcinomas, and correlated to gene copy number and mRNA
      expression. In contrast, basal-like carcinomas displayed generally lower CSPP1
      mRNA expression. Yet, a subgroup of basal-like breast carcinomas depicted nuclear
      CSPP1 expression, displayed luminal traits, and differed from nuclear CSPP1
      devoid counterparts in expression of eight genes. Eight-gene signature defined
      groups of basal-like tumours from an independent cohort showed significant
      differences in survival. CONCLUSIONS: Differential expression of a nuclear CSPP1
      isoform identified biologically and clinically distinct subgroups of basal-like
      breast carcinoma.

PMID- 24901236
TI  - Prognostic value of ABO blood group in patients with surgically resected colon
      cancer.
AB  - BACKGROUND: Previous studies supported a link between the ABO blood type and
      survival for several types of malignancies. Nonetheless, the relationship between
      ABO blood type and survival in colon cancer patients has not been rigorously
      evaluated. The goal of this retrospective analysis was to discern the
      correlations between ABO blood group and colon cancer survival. METHODS: A total
      of 1555 colon cancer patients that underwent curative-intent surgery between
      October 1995 and June 2002 were eligible for this study. The primary outcomes
      measured were the association between ABO blood group and patient survival.
      RESULTS: Compared with patients with non-AB blood types (blood types A, B, and
      O), patients with blood type AB were more likely to have better survival. The
      mean overall survival (OS) of the blood type AB patients was 113.9 months,
      whereas the mean OS of the non-AB blood type patients was significantly lower,
      106.1 months (P<0.001, log-rank test). Compared with patients with blood type AB,
      the hazard ratios for patients with A, B, and O were 4.37 (95% confidence
      interval (95% CI), 2.65-7.20), 2.99 (95% CI, 1.81-4.96), and 2.78 (95% CI, 1.69
      4.56), respectively. CONCLUSIONS: Blood type AB is a favourable prognostic factor
      for patients with colon cancer.

PMID- 24901237
TI  - Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid
      tumours and multiple myeloma.
AB  - BACKGROUND: Ficlatuzumab, a humanised hepatocyte growth factor (HGF) IgG1kappa
      inhibitory monoclonal antibody, was evaluated for recommended phase II dose
      (RP2D), safety, pharmacokinetics (PKs), antidrug antibody (ADA), pharmacodynamics
      (PDs) and antitumour activity as monotherapy or combined with erlotinib. METHODS:
      Patients with solid tumours received ficlatuzumab 2, 5, 10 or 20 mg kg(-1)
      intravenously every 2 weeks (q2w). Additional patients were treated at the RP2D
      erlotinib. RESULTS: Forty-one patients enrolled at doses ?20 mg kg(-1). Common
      adverse events (AEs) included peripheral oedema, fatigue and nausea. Three
      patients experienced grade ?3 treatment-related hyperkalaemia/hypokalaemia,
      diarrhoea or fatigue. Best overall response (44%) was stable disease (SD); median
      duration was 5.5 months (0.4-18.7 months). One patient has been on therapy with
      SD for >4 years. Pharmacokinetics of ficlatuzumab showed low clearance (0.17-0.26
      ml h(-1) kg(-1)), a half-life of 6.8-9.4 days and dose-proportional exposure.
      Ficlatuzumab/erlotinib had no impact on the PK of either agent. No ADAs were
      detected. Ficlatuzumab increased serum HGF levels. CONCLUSIONS: Recommended phase
      II dose is 20 mg kg(-1) q2w for ficlatuzumab monotherapy or with erlotinib.
      Preliminary antitumour activity and manageable AEs were observed.
      Pharmacokinetics were dose-proportional and consistent with other IgG
      therapeutics. Ficlatuzumab was not immunogenic, and serum HGF was a potential PD
      marker.

PMID- 24901238
TI  - Morphotype transition and sexual reproduction are genetically associated in a
      ubiquitous environmental pathogen.
AB  - Sexual reproduction in an environmental pathogen helps maximize its lineage
      fitness to changing environment and the host. For the fungal pathogen
      Cryptococcus neoformans, sexual reproduction is proposed to have yielded hyper
      virulent and drug resistant variants. The life cycle of this pathogen commences
      with mating, followed by the yeast-hypha transition and hyphal growth, and it
      concludes with fruiting body differentiation and sporulation. How these
      sequential differentiation events are orchestrated to ensure developmental
      continuality is enigmatic. Here we revealed the genetic network of the yeast-to
      hypha transition in Cryptococcus by analyzing transcriptomes of populations with
      a homogeneous morphotype generated by an engineered strain. Among this network,
      we found that a Pumilio-family protein Pum1 and the matricellular signal Cfl1
      represent two major parallel circuits directing the yeast-hypha transition.
      Interestingly, only Pum1 coordinates the sequential morphogenesis events during a
      alpha bisexual and alpha unisexual reproduction. Pum1 initiates the yeast-to
      hypha transition, partially through a novel filament-specific secretory protein
      Fas1; Pum1 is also required to sustain hyphal growth after the morphological
      switch. Furthermore, Pum1 directs subsequent differentiation of aerial hyphae
      into fruiting bodies in both laboratory and clinical isolates. Pum1 exerts its
      control on sexual reproduction partly through regulating the temporal expression
      of Dmc1, the meiosis-specific recombinase. Therefore, Pum1 serves a pivotal role
      in bridging post-mating morphological differentiation events with sexual
      reproduction in Cryptococcus. Our findings in Cryptococcus illustrate how an
      environmental pathogen can ensure the completion of its life cycle to safeguard
      its long-term lineage success. 

PMID- 24901239
TI  - Decreased functional connectivity and disturbed directionality of information
      flow in the electroencephalography of intensive care unit patients with delirium
      after cardiac surgery.
AB  - BACKGROUND: In this article, the authors explore functional connectivity and
      network topology in electroencephalography recordings of patients with delirium
      after cardiac surgery, aiming to improve the understanding of the pathophysiology
      and phenomenology of delirium. The authors hypothesize that disturbances in
      attention and consciousness in delirium may be related to alterations in
      functional neural interactions. METHODS: Electroencephalography recordings were
      obtained in postcardiac surgery patients with delirium (N = 25) and without
      delirium (N = 24). The authors analyzed unbiased functional connectivity of
      electroencephalography time series using the phase lag index, directed phase lag
      index, and functional brain network topology using graph analysis. RESULTS: The
      mean phase lag index was lower in the alpha band (8 to 13 Hz) in patients with
      delirium (median, 0.120; interquartile range, 0.113 to 0.138) than in patients
      without delirium (median, 0.140; interquartile range, 0.129 to 0.168; P < 0.01).
      Network topology in delirium patients was characterized by lower normalized
      weighted shortest path lengths in the alpha band (t = -2.65; P = 0.01). delta
      Band-directed phase lag index was lower in anterior regions and higher in central
      regions in delirium patients than in nondelirium patients (F = 4.53; P = 0.04,
      and F = 7.65; P < 0.01, respectively). CONCLUSIONS: Loss of alpha band functional
      connectivity, decreased path length, and increased delta band connectivity
      directed to frontal regions characterize the electroencephalography during
      delirium after cardiac surgery. These findings may explain why information
      processing is disturbed in delirium.

PMID- 24901240
TI  - Prospective external validation of a predictive score for postoperative pulmonary
      complications.
AB  - BACKGROUND: No externally validated risk score for postoperative pulmonary
      complications (PPCs) is currently available. The authors tested the
      generalizability of the Assess Respiratory Risk in Surgical Patients in Catalonia
      risk score for PPCs in a large European cohort (Prospective Evaluation of a RIsk
      Score for postoperative pulmonary COmPlications in Europe). METHODS: Sixty-three
      centers recruited 5,859 surgical patients receiving general, neuraxial, or plexus
      block anesthesia. The Assess Respiratory Risk in Surgical Patients in Catalonia
      factors (age, preoperative arterial oxygen saturation in air, acute respiratory
      infection during the previous month, preoperative anemia, upper abdominal or
      intrathoracic surgery, surgical duration, and emergency surgery) were recorded,
      along with PPC occurrence (respiratory infection or failure, bronchospasm,
      atelectasis, pleural effusion, pneumothorax, or aspiration pneumonitis).
      Discrimination, calibration, and diagnostic accuracy measures of the Assess
      Respiratory Risk in Surgical Patients in Catalonia score's performance were
      calculated for the Prospective Evaluation of a RIsk Score for postoperative
      pulmonary COmPlications in Europe cohort and three subsamples: Spain, Western
      Europe, and Eastern Europe. RESULTS: The full Prospective Evaluation of a RIsk
      Score for postoperative pulmonary COmPlications in Europe data set included 5,099
      patients; 725 PPCs were recorded for 404 patients (7.9%). The score's
      discrimination was good: c-statistic (95% CI), 0.80 (0.78 to 0.82). Predicted
      versus observed PPC rates for low, intermediate, and high risk were 0.87 and
      3.39% (score <26), 7.82 and 12.98% (>= 26 and <45), and 38.13 and 38.01% (>= 45),
      respectively; the positive likelihood ratio for a score of 45 or greater was 7.12
      (5.93 to 8.56). The score performed best in the Western Europe subsample-c
      statistic, 0.87 (0.83 to 0.90) and positive likelihood ratio, 11.56 (8.63 to
      15.47)-and worst in the Eastern Europe subsample. The predicted (5.5%) and
      observed (5.7%) PPC rates were most similar in the Spain subsample. CONCLUSIONS:
      The Assess Respiratory Risk in Surgical Patients in Catalonia score predicts
      three levels of PPC risk in hospitals outside the development setting.
      Performance differs between geographic areas.

PMID- 24901242
TI  - Fungal nail infections (onychomycosis): a never-ending story?

PMID- 24901241
TI  - Complement system in lung disease.
AB  - In addition to its established contribution to innate immunity, recent studies
      have suggested novel roles for the complement system in the development of
      various lung diseases. Several studies have demonstrated that complement may
      serve as a key link between innate and adaptive immunity in a variety of
      pulmonary conditions. However, the specific contributions of complement to lung
      diseases based on innate and adaptive immunity are just beginning to emerge.
      Elucidating the role of complement-mediated immune regulation in these diseases
      will help to identify new targets for therapeutic interventions. 

PMID- 24901243
TI  - Hypoxia and the anticoagulants dalteparin and acetylsalicylic acid affect human
      placental amino acid transport.
AB  - BACKGROUND: Anticoagulants, e.g. low-molecular weight heparins (LMWHs) and
      acetylsalicylic acid (ASA) are prescribed to women at risk for pregnancy
      complications that are associated with impaired placentation and placental
      hypoxia. Beyond their role as anticoagulants these compounds exhibit direct
      effects on trophoblast but their impact on placental function is unknown. The
      amino acid transport systems A and L, which preferably transfer essential amino
      acids, are well-described models to study placental nutrient transport. We aimed
      to examine the effect of hypoxia, LMWHs and ASA on the activity of the placental
      amino acid transport systems A and L and associated signalling mechanisms.
      METHODS: The uptake of C14-MeAIB (system A) or H3-leucin (system L) was
      investigated after incubation of primary villous fragments isolated from term
      placentas. Villous tissue was incubated at 2% O2 (hypoxia), 8% O2 and standard
      culture conditions (21% O2) or at 2% O2 and 21% O2 with dalteparin or ASA.
      Activation of the JAK/STAT or mTOR signalling pathways was determined by Western
      analysis of total and phosphorylated STAT3 or Raptor. RESULTS: Hypoxia decreased
      system A mediated MeAIB uptake and increased system L mediated leucine uptake
      compared to standard culture conditions (21% O2). This was accompanied by an
      impairment of STAT3 and a stimulation of Raptor signalling. System L activity
      increased at 8% O2. Dalteparin treatment reduced system A and system L activity
      under normoxic conditions and ASA (1 mM) decreased system A and L transporter
      activity under normoxic and hypoxic conditions. CONCLUSIONS: Our data underline
      the dependency of placental function on oxygen supply. LMWHs and ASA are not able
      to reverse the effects of hypoxia on placental amino acid transport. These
      findings and the uncovering of the signalling mechanisms in more detail will help
      to understand the impact of LMWHs and ASA on placental function and fetal growth.

PMID- 24901244
TI  - Contact calls of the northern and southern white rhinoceros allow for individual
      and species identification.
AB  - Inter-individual relationships particularly in socially living mammals often
      require a well-developed communication system. Vocal and olfactory signals are
      the most important for the communication of rhinos, however, their vocal
      communication has been investigated to a very limited extent so far. White rhinos
      have the most developed social system out of all the rhinoceros species and vocal
      signals might therefore play an important role in their social interactions. We
      recorded repetitive contact pant calls from six captive northern white rhinos
      (Ceratotherium cottoni) and 14 captive and free-ranging southern white rhinos
      (Ceratotherium simum) and examined if they transmit information about individual
      identity, species, social context and age class. Discriminant analyses revealed
      that a high percentage of the pant calls of both species could be classified to a
      correct individual. We calculated signature information capacity of pant calls
      recorded from adult animals in isolation at 3.19 bits for the northern white
      rhinos and at 3.15 bits for the southern white rhinos, which can potentially
      allow for a vocal discrimination of nine individuals of both species. We found
      that pant calls varied by species. Northern white rhinos had longer calls and
      also differed from the southern white rhinos in several frequency parameters of
      their calls. We also analysed the pant calls of southern white rhinos for the
      differences between the age classes and between social contexts in which they
      were recorded. Our results show that pant calls carry information about
      individual, species, age class and context. The ability to recognize this
      information would allow rhinos, in addition to olfactory cues, to communicate
      with highly increased accuracy. A better understanding of communication of white
      rhinos has potential practical use in their management and conservation
      particularly because of the low breeding success of white rhinos in captivity. 

PMID- 24901246
TI  - Anxious mood narrows attention in feature space.
AB  - Spatial attention can operate like a spotlight whose scope can vary depending on
      task demands. Emotional states contribute to the spatial extent of attentional
      selection, with the spotlight focused more narrowly during anxious moods and more
      broadly during happy moods. In addition to visual space, attention can also
      operate over features, and we show here that mood states may also influence
      attentional scope in feature space. After anxious or happy mood inductions,
      participants focused their attention to identify a central target while ignoring
      flanking items. Flankers were sometimes coloured differently than targets, so
      focusing attention on target colour should lead to relatively less interference.
      Compared to happy and neutral moods, when anxious, participants showed reduced
      interference when colour isolated targets from flankers, but showed more
      interference when flankers and targets were the same colour. This pattern reveals
      that the anxious mood caused these individuals to attend to the irrelevant
      feature in both cases, regardless of its benefit or detriment. In contrast,
      participants showed no effect of colour on interference when happy, suggesting
      that positive mood did not influence attention in feature space. These mood
      effects on feature-based attention provide a theoretical bridge between previous
      findings concerning spatial and conceptual attention. 

PMID- 24901247
TI  - Well-defined mono(eta(3)-allyl)nickel complex =MONi(eta(3)-C3H5) (M = Si or Al)
      grafted onto silica or alumina: a molecularly dispersed nickel precursor for
      syntheses of supported small size nickel nanoparticles.
AB  - Preparing evenly-dispersed small size nickel nanoparticles over inert oxides
      remains a challenge today. In this context, a versatile method to prepare
      supported small size nickel nanoparticles (ca. 1-3 nm) with narrow size
      distribution via a surface organometallic chemistry (SOMC) route is described.
      The grafted mono(eta(3)-allyl)nickel complexes =MONi(eta(3)-C3H5) (M = Si or Al)
      as precursors are synthesized and fully characterized by elemental analysis, FTIR
      spectroscopy and paramagnetic solid-state NMR.

PMID- 24901248
TI  - Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft
      growth and development.
AB  - Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way
      for development of targeted therapies. Robust model systems such as orthotopic
      xenografts are necessary for testing such therapeutics. One system involves
      bioluminescence imaging of luciferase-expressing human retinoblastoma cells
      injected into the vitreous of newborn rat eyes. Although used for several drug
      studies, the spatial and temporal development of tumors in this model has not
      been documented. Here, we present a new model to allow analysis of average
      luciferin flux ([Formula: see text]) through the tumor, a more biologically
      relevant parameter than peak bioluminescence as traditionally measured. Moreover,
      we monitored the spatial development of xenografts in the living eye. We
      engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced
      green fluorescent protein-luciferase fusion protein. In intravitreal xenografts,
      we assayed bioluminescence and computed [Formula: see text], as well as
      documented tumor growth by intraocular optical coherence tomography (OCT),
      brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor
      size, and ex vivo fluorescent signal were all highly correlated in orthotopic
      xenografts. By OCT, xenografts were dense and highly vascularized, with well
      defined edges. Small tumors preferentially sat atop the optic nerve head; this
      morphology was confirmed on histological examination. In vivo, [Formula: see
      text] in xenografts showed a plateau effect as tumors became bounded by the
      dimensions of the eye. The combination of [Formula: see text] modeling and in
      vivo intraocular imaging allows both quantitative and high-resolution, non
      invasive spatial analysis of this retinoblastoma model. This technique will be
      applied to other cell lines and experimental therapeutic trials in the future. 

PMID- 24901249
TI  - Glabridin mediate caspases activation and induces apoptosis through JNK1/2 and
      p38 MAPK pathway in human promyelocytic leukemia cells.
AB  - BACKGROUND: Glabridin, a prenylated isoflavonoid of G. glabra L. roots, has been
      associated with a wide range of biological properties such as regulation of
      energy metabolism, estrogenic, neuroprotective, anti-osteoporotic, and skin
      whitening in previous studies. However, the effect of glabridin on tumor cells
      metastasis has not been clearly clarified. Here, the molecular mechanism by which
      glabridin anticancer effects in human promyelocytic leukemia cells was
      investigated. METHODOLOGY AND PRINCIPAL FINDINGS: The results showed that
      glabridin significantly inhibited cell proliferation of four AML cell lines (HL
      60, MV4-11, U937, and THP-1). Furthermore, glabridin induced apoptosis of HL-60
      cells through caspases-3, -8, and -9 activations and PARP cleavage in dose- and
      time-dependent manner. Moreover, western blot analysis also showed that glabridin
      increase phosphorylation of ERK1/2, p38 MAPK and JNK1/2 in dose- and time
      dependent manner. Inhibition of p38 MAPK and JNK1/2 by specific inhibitors
      significantly abolished the glabridin-induced activation of the caspase-3, -8 and
      -9. CONCLUSION: Taken together, our results suggest that glabridin induced HL-60
      cell apoptosis through p38 MAPK and JNK1/2 pathways and could serve as a
      potential additional chemotherapeutic agent for treating AML.

PMID- 24901250
TI  - The self-limiting dynamics of TGF-beta signaling in silico and in vitro, with
      negative feedback through PPM1A upregulation.
AB  - The TGF-beta/Smad signaling system decreases its activity through strong negative
      regulation. Several molecular mechanisms of negative regulation have been
      published, but the relative impact of each mechanism on the overall system is
      unknown. In this work, we used computational and experimental methods to assess
      multiple negative regulatory effects on Smad signaling in HaCaT cells. Previously
      reported negative regulatory effects were classified by time-scale: degradation
      of phosphorylated R-Smad and I-Smad-induced receptor degradation were slow-mode
      effects, and dephosphorylation of R-Smad was a fast-mode effect. We modeled
      combinations of these effects, but found no combination capable of explaining the
      observed dynamics of TGF-beta/Smad signaling. We then proposed a negative
      feedback loop with upregulation of the phosphatase PPM1A. The resulting model was
      able to explain the dynamics of Smad signaling, under both short and long
      exposures to TGF-beta. Consistent with this model, immuno-blots showed PPM1A
      levels to be significantly increased within 30 min after TGF-beta stimulation.
      Lastly, our model was able to resolve an apparent contradiction in the published
      literature, concerning the dynamics of phosphorylated R-Smad degradation. We
      conclude that the dynamics of Smad negative regulation cannot be explained by the
      negative regulatory effects that had previously been modeled, and we provide
      evidence for a new negative feedback loop through PPM1A upregulation. This work
      shows that tight coupling of computational and experiments approaches can yield
      improved understanding of complex pathways. 

PMID- 24901251
TI  - Crystal structure of the open state of the Neisseria gonorrhoeae MtrE outer
      membrane channel.
AB  - Active efflux of antimicrobial agents is one of the most important strategies
      used by bacteria to defend against antimicrobial factors present in their
      environment. Mediating many cases of antibiotic resistance are transmembrane
      efflux pumps, composed of one or more proteins. The Neisseria gonorrhoeae MtrCDE
      tripartite multidrug efflux pump, belonging to the hydrophobic and amphiphilic
      efflux resistance-nodulation-cell division (HAE-RND) family, spans both the inner
      and outer membranes of N. gonorrhoeae and confers resistance to a variety of
      antibiotics and toxic compounds. We here describe the crystal structure of N.
      gonorrhoeae MtrE, the outer membrane component of the MtrCDE tripartite multidrug
      efflux system. This trimeric MtrE channel forms a vertical tunnel extending down
      contiguously from the outer membrane surface to the periplasmic end, indicating
      that our structure of MtrE depicts an open conformational state of this channel. 

PMID- 24901253
TI  - Political differences in past, present, and future life satisfaction: Republicans
      are more sensitive than democrats to political climate.
AB  - Previous research finds that Republicans report being happier or more satisfied
      with their lives than Democrats. Using representative American samples from 2002,
      2005, 2007, 2009, and 2010, we tested a Person * Situation interactionist account
      in which political affiliation (Democrat, Republican) and political climate
      (favorable when the president in office is of the same party) are proposed to
      affect past, present, and anticipated future life satisfaction. Meta-analyses of
      related tests of key hypotheses confirmed that (a) life satisfaction was greater
      when the political climate was favorable rather than unfavorable and (b)
      Republicans were more sensitive to political climate than Democrats. As
      predicted, Republicans also were more politically polarized than Democrats. Taken
      together, the findings indicate that, compared to Democrats, Republicans are more
      apt to self-identify in political terms, and core aspects of their subjective
      well-being are more easily affected by the outcome of political events. 

PMID- 24901255
TI  - Development of AMOEBA force field for 1,3-dimethylimidazolium based ionic
      liquids.
AB  - The development of AMOEBA (a multipolar polarizable force field) for imidazolium
      based ionic liquids is presented. Our parametrization method follows the AMOEBA
      procedure and introduces the use of QM intermolecular total interactions as well
      as QM energy decomposition analysis (EDA) to fit individual interaction energy
      components. The distributed multipoles for the cation and anions have been
      derived using both the Gaussian distributed multipole analysis (GDMA) and
      Gaussian electrostatic model-distributed multipole (GEM-DM) methods.1 The
      intermolecular interactions of a 1,3-dimethylimidazolium [dmim(+)] cation with
      various anions, including fluoride [F(-)], chloride [Cl(-)], nitrate [NO(3)(-)],
      and tetraflorouborate [BF(4)(-)], were studied using quantum chemistry
      calculations at the MP2/6-311G(d,p) level of theory. Energy decomposition
      analysis was performed for each pair using the restricted variational space
      decomposition approach (RVS) at the HF/6-311G(d,p) level. The new force field was
      validated by running a series of molecular dynamic (MD) simulations and by
      analyzing thermodynamic and structural properties of these systems. A number of
      thermodynamic properties obtained from MD simulations were compared with
      available experimental data. The ionic liquid structure reproduced using the
      AMOEBA force field is also compared with the data from neutron diffraction
      experiment and other MD simulations. Employing GEM-DM force fields resulted in a
      good agreement on liquid densities rho, enthalpies of vaporization DeltaH(vap),
      and diffusion coefficients D(+/-) in comparison with conventional force fields.

PMID- 24901254
TI  - Cholesterol-induced non-alcoholic fatty liver disease and atherosclerosis
      aggravated by systemic inflammation.
AB  - Although triglyceride accumulation in the liver causes non-alcoholic fatty liver
      disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as
      atherosclerosis. However, NAFLD and atherosclerosis have not been investigated
      simultaneously in animal models fed a high-cholesterol diet. Moreover, it is
      unclear whether systemic inflammation can exacerbate both pathologies in the same
      model. Accordingly, this study investigated the effect of additional systemic
      inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild
      animals. New Zealand white rabbits were divided into 4 groups: groups I (control)
      and II received normal chow, and groups III and IV received a 1% cholesterol
      diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II
      and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3
      weeks. After 3 months, total cholesterol markedly increased in groups III and IV,
      and the serum expressions of systemic inflammatory markers were elevated in the
      groups II-IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with
      sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of
      foam cells) were observed in both the liver and aorta specimens from group III,
      and advanced lesions were observed in group IV. The expressions of inflammatory
      cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group
      I to IV but were similar in the liver in groups II-IV. Cholesteryl ester (CE)
      levels were higher in group IV than in group III, although the difference was not
      significant. CE levels in the aorta were similar between groups III and IV.
      Systemic inflammation can simultaneously exacerbate existing early lesions due to
      cholesterol overload in both the liver and aorta of rabbits. However, the
      cellular response of inflammatory receptors and expression of cholesterol
      metabolites differ between these organs. 

PMID- 24901252
TI  - Sequence of a complete chicken BG haplotype shows dynamic expansion and
      contraction of two gene lineages with particular expression patterns.
AB  - Many genes important in immunity are found as multigene families. The
      butyrophilin genes are members of the B7 family, playing diverse roles in co
      regulation and perhaps in antigen presentation. In humans, a fixed number of
      butyrophilin genes are found in and around the major histocompatibility complex
      (MHC), and show striking association with particular autoimmune diseases. In
      chickens, BG genes encode homologues with somewhat different domain organisation.
      Only a few BG genes have been characterised, one involved in actin-myosin
      interaction in the intestinal brush border, and another implicated in resistance
      to viral diseases. We characterise all BG genes in B12 chickens, finding a
      multigene family organised as tandem repeats in the BG region outside the MHC, a
      single gene in the MHC (the BF-BL region), and another single gene on a different
      chromosome. There is a precise cell and tissue expression for each gene, but
      overall there are two kinds, those expressed by haemopoietic cells and those
      expressed in tissues (presumably non-haemopoietic cells), correlating with two
      different kinds of promoters and 5' untranslated regions (5'UTR). However, the
      multigene family in the BG region contains many hybrid genes, suggesting
      recombination and/or deletion as major evolutionary forces. We identify BG genes
      in the chicken whole genome shotgun sequence, as well as by comparison to other
      haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic
      expansion and contraction within the BG region. Thus, the BG genes in chickens
      are undergoing much more rapid evolution compared to their homologues in mammals,
      for reasons yet to be understood. 

PMID- 24901257
TI  - N-Substituted hydroxylamines as synthetically versatile amino sources in the
      iridium-catalyzed mild C-H amidation reaction.
AB  - N-Substituted hydroxylamines such as aroyloxy- or acyloxycarbamates were
      successfully employed as synthetically versatile amino precursors in the iridium
      catalyzed direct C-H amidation of arenes. The reaction proceeds smoothly at room
      temperature over a broad range of substrates with high functional group tolerance
      to afford N-substituted arylamine products. 

PMID- 24901256
TI  - Disseminated Mycobacterium bovis infection in red foxes (Vulpes vulpes) with
      cerebral involvement found in Portugal.
AB  - A total of 49 road-killed red foxes were used for the detection of Mycobacterium
      tuberculosis complex (MTC) in Portugal. MTC infection was detected by PCR in 10
      red foxes (20.4%; 95% confidence interval [CI] 8.8-31.2%) and confirmed in three
      (6.1%; 95% CI 0.0-7.9%) of them by microbiological culture. The complex was
      detected in 20 tissues out of 441 by PCR techniques (4.5%; 95% CI 16.3-23.7%) and
      in seven tissues out of 441 (1.6%; 95% CI 4.6-9.4%) by culture. MTC was most
      frequently detected in the brain (8.2%) and in the mediastinal lymph nodes
      (8.2%). The seven cultures obtained were positive for M. bovis by PCR-based
      genotyping of the MTC targeting genomic deletions. This study confirms the
      presence of disseminated M. bovis in red foxes in Portugal, and it is the first
      report in the world of the natural infection in the animals' brains.

PMID- 24901258
TI  - Directed progression brain networks in Alzheimer's disease: properties and
      classification.
AB  - This article introduces a new approach in brain connectomics aimed at
      characterizing the temporal spread in the brain of pathologies like Alzheimer's
      disease (AD). The main instrument is the development of "directed progression
      networks" (DPNets), wherein one constructs directed edges between nodes based on
      (weakly) inferred directions of the temporal spreading of the pathology. This
      stands in contrast to many previously studied brain networks where edges
      represent correlations, physical connections, or functional progressions. In
      addition, this is one of a few studies showing the value of using directed
      networks in the study of AD. This article focuses on the construction of DPNets
      for AD using longitudinal cortical thickness measurements from magnetic resonance
      imaging data. The network properties are then characterized, providing new
      insights into AD progression, as well as novel markers for differentiating normal
      cognition (NC) and AD at the group level. It also demonstrates the important role
      of nodal variations for network classification (i.e., the significance of
      standard deviations, not just mean values of nodal properties). Finally, the
      DPNets are utilized to classify subjects based on their global network measures
      using a variety of data-mining methodologies. In contrast to most brain networks,
      these DPNets do not show high clustering and small-world properties.

PMID- 24901259
TI  - Causes of death among HIV-infected patients in France in 2010 (national survey):
      trends since 2000.
AB  - OBJECTIVE: The Mortalite 2010 survey aimed at describing the causes of death
      among HIV-infected patients in France in 2010 and their evolution since 2000.
      DESIGN AND METHODS: A national sample of clinical sites, providing HIV care and
      treatment, notified and documented deaths using a standardized questionnaire.
      RESULTS: The 90 participating wards notified 728 deaths. Median age at death was
      50 years (interquartile range 45-58) and 75% were men. The main underlying causes
      of death were AIDS-related (25% in 2010 vs. 36% in 2005 and 47% in 2000), non
      AIDS non-viral hepatitis-related malignancy (22 vs. 17 and 11%), liver-related
      (11 vs. 15 and 13%), cardiovascular diseases (10 vs. 8 and 7%) and non-AIDS
      related infections (9 vs. 4 and 7%). Malignancies (AIDS and non-AIDS-related)
      accounted for a third of all causes of death. AIDS accounted for 33% of all
      causes of death among patients mono-infected with HIV vs. only 13% among those co
      infected with hepatitis B virus or hepatitis C virus. CONCLUSION: In 2010, 25% of
      the causes of death among HIV-infected patients remained AIDS-related. Improved
      screening and earlier HIV treatment should lead to a smaller proportion of deaths
      due to AIDS. The majority of patients died of various causes, whereas their HIV
      infection was well controlled under treatment. Improving case management of HIV
      infected patients should include a multidisciplinary approach (prevention,
      screening, treatment), especially in oncology. Smoking cessation should be a
      priority goal.

PMID- 24901262
TI  - Effects of polyquaternium- and benzalkonium-chloride-preserved travoprost on
      ocular surfaces: an impression cytology study.
AB  - PURPOSE: To compare the toxicity effect of polyquaternium (PQ) and benzalkonium
      chloride (BAK) preservation of travoprost on the ocular surface. METHODS: This
      prospective study included 44 eyes of 44 patients with newly diagnosed glaucoma.
      Twenty-two patients used PQ-preserved travoprost (PQ group) and 22 patients used
      BAK-preserved travoprost (BAK group). To investigate the effect on the ocular
      surface, conjunctival impression cytology (IC) was performed at baseline and the
      1- and 6-month follow-up visits. Additionally, the ocular surface disease index
      (OSDI) questionnaire, Schirmer I test, and tear break-up time (TBUT) measurement
      were administered at baseline, and at 1-, 3-, and 6-month follow-up visits.
      RESULTS: While both groups showed statistically significant IC grade increases at
      1 and 6 months when compared with baseline measurements, IC grades were
      significantly higher for patients using PQ-preserved travoprost compared with
      patients using BAK-preserved travoprost. The Schirmer I test and TBUT scores were
      not statistically significant between group 1 and BAK group at baseline and at 1
      , 3-, and 6-month visits (P>0.05). OSDI scores did not statistically differ at
      baseline and the 1-month measurements between the 2 groups (P>0.05), but the 3-
      and 6-month OSDI scores were significantly higher for BAK group (P=0.001).
      Differences in OSDI and Schirmer I test scores were statistically significant at
      1, 3, and 6 months in both groups as compared with baseline values (P<0.05).
      Statistically significant differences in the TBUT scores were seen for both
      groups at 3 and 6 months, while BAK group, but not PQ group, had insignificant
      score differences at 1 month as compared with baseline values of PQ group
      (P=0.083). CONCLUSION: PQ-preserved travoprost was found to be safer and better
      tolerated than BAK-preserved travoprost. PQ-preserved travoprost provided better
      ocular surface comfort, and therefore a better patient experience, which would
      likely result in higher treatment compliance.

PMID- 24901263
TI  - Intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy is the most common pregnancy-specific liver
      disease that typically presents in the third trimester. The clinical features are
      maternal pruritus in the absence of a rash and deranged liver function tests,
      including raised serum bile acids. Intrahepatic cholestasis of pregnancy is
      associated with an increased risk of adverse perinatal outcomes, including
      spontaneous preterm delivery, meconium staining of the amniotic fluid, and
      stillbirth. It is commonly treated with ursodeoxycholic acid. There is
      accumulating evidence to suggest that intrahepatic cholestasis of pregnancy has a
      lasting influence on both maternal and fetal health. We review the etiology,
      diagnosis, and management of this intriguing condition. 

PMID- 24901260
TI  - Recent developments in novel antidepressants targeting alpha4beta2-nicotinic
      acetylcholine receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing
      drugs that can potentially treat various central nervous system disorders.
      Considerable evidence supports the hypothesis that modulation of the cholinergic
      system through activation and/or desensitization/inactivation of nAChR holds
      promise for the development of new antidepressants. The introductory portion of
      this Miniperspective discusses the basic pharmacology that underpins the
      involvement of alpha4beta2-nAChRs in depression, along with the structural
      features that are essential to ligand recognition by the alpha4beta2-nAChRs. The
      remainder of this Miniperspective analyzes reported nicotinic ligands in terms of
      drug design considerations and their potency and selectivity, with a particular
      focus on compounds exhibiting antidepressant-like effects in preclinical or
      clinical studies. This Miniperspective aims to provide an in-depth analysis of
      the potential for using nicotinic ligands in the treatment of depression, which
      may hold some promise in addressing an unmet clinical need by providing relief
      from depressive symptoms in refractory patients. 

PMID- 24901264
TI  - Hemostatic dysfunction with acute fatty liver of pregnancy.
AB  - OBJECTIVE: To estimate the frequency of disseminated intravascular coagulation
      (DIC); elucidate the genesis of hemostatic dysfunction; and characterize
      associated hemolysis in women with acute fatty liver of pregnancy. METHODS:
      Hemostatic function was measured in 51 women. Disseminated intravascular
      coagulation was assessed using the International Society of Thrombosis and
      Haemostasis DIC score. Hepatic and hemostatic function was quantified with
      measurement of fibrinogen, fibrin-fibrinogen split products, cholesterol, and
      coagulation testing. As a comparison of fibrinogen synthesis, these women were
      compared with 25 women with placental abruption. Hemolysis was assessed
      indirectly by quantification of reticulocytosis and nucleated red blood cells
      with determination of erythrocyte morphotypes. RESULTS: Eighty-percent of women
      were classified as having unequivocal DIC (mean score 5.9+/-1.8) at delivery,
      which persisted 4-5 days postpartum. Fibrinogen regeneration with placental
      abruption was rapid, whereas it remained depressed for 4-5 days with acute fatty
      liver of pregnancy; fibrin-fibrinogen split products were also cleared more
      rapidly after abruption than women with acute fatty liver (P<.001 for interaction
      for both using random effects modeling). Kaplan-Meier survival analysis of
      fibrinogen recovery to a set point of 280 mg/dL after delivery was also different
      between the two cohorts (median 1.7 compared with 4.2 days, P=.046). Continuing
      hepatic dysfunction with acute fatty liver of pregnancy was exemplified by
      diminished procoagulant production. Reticulocytosis, nucleated red blood cells,
      and elevated serum bilirubin levels reflected ongoing hemolysis. CONCLUSIONS:
      Hemostatic dysfunction with acute fatty liver of pregnancy persists 4-5 days
      postpartum and results from substantive ongoing DIC in concert with reduced
      procoagulant synthesis and clinically significant hemolysis. LEVEL OF EVIDENCE: :
      III.

PMID- 24901265
TI  - Neonatal and maternal outcomes with prolonged second stage of labor.
AB  - OBJECTIVE: To assess neonatal and maternal outcomes when the second stage of
      labor was prolonged according to American College of Obstetricians and
      Gynecologists guidelines. METHODS: Electronic medical record data from a
      retrospective cohort (2002-2008) from 12 U.S. clinical centers (19 hospitals),
      including 43,810 nulliparous and 59,605 multiparous singleton deliveries at 36
      weeks of gestation or greater, vertex presentation, who reached 10-cm cervical
      dilation were analyzed. Prolonged second stage was defined as: nulliparous women
      with epidural greater than 3 hours and without greater than 2 hours and
      multiparous women with epidural greater than 2 hours and without greater than 1
      hour. Maternal and neonatal outcomes were compared and adjusted odds ratios
      calculated controlling for maternal race, body mass index, insurance, and region.
      RESULTS: Prolonged second stage occurred in 9.9% and 13.9% of nulliparous and
      3.1% and 5.9% of multiparous women with and without an epidural, respectively.
      Vaginal delivery rates with prolonged second stage compared with within
      guidelines were 79.9% compared with 97.9% and 87.0% compared with 99.4% for
      nulliparous women with and without epidural, respectively, and 88.7% compared
      with 99.7% and 96.2% compared with 99.9% for multiparous women with and without
      epidural, respectively (P<.001 for all comparisons). Prolonged second stage was
      associated with increased chorioamnionitis and third-degree or fourth-degree
      perineal lacerations. Neonatal morbidity with prolonged second stage included
      sepsis in nulliparous women (with epidural: 2.6% compared with 1.2% [adjusted
      odds ratio (OR) 2.08, 95% confidence interval (CI) 1.60-2.70]; without epidural:
      1.8% compared with 1.1% [adjusted OR 2.34, 95% CI 1.28-4.27]); asphyxia in
      nulliparous women with epidural (0.3% compared with 0.1% [adjusted OR 2.39, 95%
      CI 1.22-4.66]) and perinatal mortality without epidural (0.18% compared with
      0.04% for nulliparous women [adjusted OR 5.92, 95% CI 1.43-24.51]); and 0.21%
      compared with 0.03% for multiparous women (adjusted OR 6.34, 95% CI 1.32-30.34).
      However, among the offspring of women with epidurals whose second stage was
      prolonged (3,533 nulliparous and 1,348 multiparous women), there were no cases of
      hypoxic-ischemic encephalopathy or perinatal death. CONCLUSIONS: Benefits of
      increased vaginal delivery should be weighed against potential small increases in
      maternal and neonatal risks with prolonged second stage. LEVEL OF EVIDENCE: : II.

PMID- 24901267
TI  - Executive summary of the reVITALize initiative: standardizing obstetric data
      definitions.
AB  - Precision in language has become critically important with the evolution of the
      electronic medical record and proliferation of measurement in vital statistics
      and health care. Taking the opportunity to standardize clinical definitions is a
      fundamental step in building a robust national data infrastructure that is useful
      and useable for clinicians and patients. The reVITALize Initiative leads and
      coordinates a national multidisciplinary movement to standardize obstetric data
      definitions for written and verbal clinical communication, electronic health
      record data capture, vital statistics and public health surveillance,
      measurement, quality improvement, reporting, and research. 

PMID- 24901266
TI  - Association of copy number variants with specific ultrasonographically detected
      fetal anomalies.
AB  - OBJECTIVE: To evaluate the association of other-than-common benign copy number
      variants with specific fetal abnormalities detected by ultrasonogram. METHODS:
      Fetuses with structural anomalies were compared with fetuses without detected
      abnormalities for the frequency of other-than-common benign copy number variants.
      This is a secondary analysis from the previously published National Institute of
      Child Health and Human Development microarray trial. Ultrasound reports were
      reviewed and details of structural anomalies were entered into a nonhierarchical
      web-based database. The frequency of other-than-common benign copy number
      variants (ie, either pathogenic or variants of uncertain significance) not
      detected by karyotype was calculated for each anomaly in isolation and in the
      presence of other anomalies and compared with the frequency in fetuses without
      detected abnormalities. RESULTS: Of 1,082 fetuses with anomalies detected on
      ultrasound scan, 752 had a normal karyotype. Other-than-common benign copy number
      variants were present in 61 (8.1%) of these euploid fetuses. Fetuses with
      anomalies in more than one system had a 13.0% frequency of other-than-common
      benign copy number variants, which was significantly higher (P<.001) than the
      frequency (3.6%) in fetuses without anomalies (n=1,966). Specific organ systems
      in which isolated anomalies were nominally significantly associated with other
      than-common benign copy number variants were the renal (P=.036) and cardiac
      systems (P=.012) but did not meet significance after the adjustment. CONCLUSIONS:
      When a fetal anomaly is detected on ultrasonogram, chromosomal microarray offers
      additional information over karyotype, the degree of which depends on the organ
      system involved. LEVEL OF EVIDENCE: : II.

PMID- 24901268
TI  - Factors associated with human papillomavirus vaccination completion on a catch-up
      schedule.
AB  - OBJECTIVE: "Catch-up vaccination" is vaccination outside of the recommended
      schedule and may occur between 13 and 26 years of age for human papillomavirus
      vaccines. We aimed to characterize those adolescents and young women who were
      most likely to complete the three-vaccine series on a catch-up schedule. METHODS:
      We performed a retrospective review of adolescents and young women aged 13-26
      years who initiated human papillomavirus vaccination between January 2007 and
      April 2009 and followed them through April 2010 for vaccine completion (n=310).
      Completion was defined as receipt of three doses of the human papillomavirus
      vaccine. We used log binomial regression to investigate characteristics
      associated with vaccine completion. The main exposure was pregnancy occurring
      within 1 year of initiating the series. Other exposure variables included age,
      race, insurance, and clinical site. RESULTS: Fifty-six percent of participants
      completed the vaccine series with a mean follow-up of 2 years. After adjusting
      for age and site of vaccination, those who became pregnant (n=31) were
      significantly less likely than those who did not to complete the series (22.6%
      compared with 59.9%, respectively, adjusted relative risk 0.42, 95% confidence
      interval [CI] 0.21-0.81). Race or ethnicity was also independently associated
      with completion, with black patients having the lowest completion rate (48%
      compared with 72.1% among white patients, adjusted relative risk 0.71, 95% CI
      0.54-0.91). CONCLUSION: Human papillomavirus vaccination completion is low among
      adolescents and females receiving vaccination on a catch-up schedule. Those who
      become pregnant may not resume the series after pregnancy. Vaccine initiation is
      an opportunity for contraceptive provision for adolescents and young women. LEVEL
      OF EVIDENCE: : II.

PMID- 24901269
TI  - Placental transfusion strategies in very preterm neonates: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To investigate the effects of interventions promoting placental
      transfusion at delivery (delayed cord clamping or umbilical cord milking)
      compared with early cord clamping on outcomes among premature neonates of less
      than 32 weeks of gestation. DATA SOURCES: A systematic search was conducted of
      PubMed, Embase, and ClinicalTrials.gov databases (January 1965 to December 2013)
      for articles relating to placental transfusion strategies in very preterm
      neonates. METHODS OF STUDY SELECTION: Literature searches returned 369 articles
      with 82 considered in full. We only included data from studies with an average
      gestational age of less than 32 weeks of gestation enrolled in randomized trials
      of enhanced placental-fetal transfusion interventions (delayed cord clamping or
      umbilical cord milking) compared with early cord clamping. TABULATION,
      INTEGRATION, AND RESULTS: We identified 12 eligible studies describing a total of
      531 neonates with an average gestation of 28 weeks. Benefits of greater placental
      transfusion were decreased mortality (eight studies, risk ratio 0.42, 95%
      confidence interval [CI] 0.19-0.95, 3.4% compared with 9.3%, P=.04), lower
      incidence of blood transfusions (six studies, risk ratio 0.75, 95% CI 0.63-0.92,
      49.3% compared with 66%, P<.01), and lower incidence of intraventricular
      hemorrhage (nine studies, risk ratio 0.62, 95% CI 0.43-0.91, 16.7% compared with
      27.3%, P=.01). There was a weighted mean difference of -1.14 blood transfusions
      (six studies, 95% CI -2.01-0.27, P<.01) and a 3.24-mmHg increase in blood
      pressure at 4 hours of life (four studies, 95% CI 1.76-4.72, P<.01). No
      differences were observed between the groups across all available safety measures
      (5-minute Apgar scores, admission temperature, incidence of delivery room
      intubation, peak serum bilirubin levels). CONCLUSIONS: Results of this meta
      analysis suggest that enhanced placental transfusion (delayed umbilical cord
      clamping or umbilical cord milking) at birth provides better neonatal outcomes
      than does early cord clamping, most notably reductions in overall mortality,
      lower risk of intraventricular hemorrhage, and decreased blood transfusion
      incidence. The optimal umbilical cord clamping practice among neonates requiring
      immediate resuscitation remains uncertain.

PMID- 24901270
TI  - Improving maternal and infant health outcomes in Medicaid and the Children's
      Health Insurance Program.
AB  - Maternal and infant health is critical to our nation's health. Disparities remain
      unacceptably high, particularly in the areas of prematurity and infant mortality.
      In 2012, traditionally distant partners such as federal and state governments,
      Medicaid and commercial payers, patients, public health and private clinicians,
      and multiple advocacy groups collaborated to focus on improving birth outcomes.
      To catalyze the alignment, the Centers for Medicare and Medicaid Services
      convened an Expert Panel on Improving Maternal and Infant Health Outcomes in
      Medicaid and the Children's Health Insurance Program. Over a year's time, the
      Expert Panel assimilated the best available evidence in clinical science and
      policy from content leaders and patients. These recommendations culminated in the
      present report, which challenges us as a nation to implement strategies to help
      all children have the best chance to survive and thrive comparable to that of
      other westernized nations. 

PMID- 24901271
TI  - Reducing postoperative pain after tubal ligation with rings or clips: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of using local anesthesia during interval
      laparoscopic tubal ligation to control postoperative pain. DATA SOURCES: We
      searched MEDLINE, PubMed, and Cochrane databases and found additional articles
      from bibliographies of relevant studies. METHODS OF STUDY SELECTION: We included
      only randomized, double-blind, placebo-controlled trials reporting postoperative
      pain after interval laparoscopic tubal ligation under general anesthesia (n=20).
      The trials compared the application of topical or injectable local anesthetic
      with placebo and used a visual analog scale (VAS) (scores 0-100) or the Modified
      McGill Pain Intensity Scale (subsequently converted to a VAS) to assess pain.
      TABULATION, INTEGRATION, AND RESULTS: Pain scores were evaluated at the following
      times after extubation: 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24
      hours. The meta-analysis was based on random-effects methods for pooled data
      using RevMan. Postoperative pain decreased with the use of local anesthetic
      compared with placebo as follows (mean VAS decrease in millimeters, 95%
      confidence interval): 30 minutes 18.6 (11.7-25.5); 1 hour 16.6 (9.3-24.0); 2
      hours 17.4 (9.6-25.2); 4 hours 12.5 (5.1-19.9); 8 hours 11.9 (6.7-17.1); and 24
      hours 3.9 (-1.4 to 9.2). There was moderate heterogeneity in the data across
      studies (I statistic ranging from 55% to 75%). The effect size was similar for
      the following subgroups: pain scores reported as means or medians and use of
      McGill compared with VAS pain scales. A stratified analysis of trials including
      ring tubal ligation compared with clip tubal ligation showed the use of local
      anesthetic decreased pain substantially for both. No eligible studies assessed
      tubal ligation with cautery. CONCLUSION: Use of local anesthetic during
      laparoscopic tubal ligation substantially reduces postoperative pain up to 8
      hours after surgery.

PMID- 24901273
TI  - Steps toward a national disaster plan for obstetrics.
AB  - Hospitals play a central role in disasters by receiving an influx of casualties
      and coordinating medical efforts to manage resources. However, plans have not
      been fully developed in the event the hospital itself is severely damaged, either
      from natural disasters like earthquakes or tornados or manmade events such as a
      massive electrical failure or terrorist attacks. Of particular concern is the
      limited awareness of the obstetric units' specialized needs in the world of
      disaster planning. Within the same footprint of any obstetric unit, there exists
      a large variety of patient acuity and needs including laboring women,
      postoperative patients, and healthy postpartum patients with their newborns. An
      obstetric-specific triage method is paramount to accurately assess and rapidly
      triage patients during a disaster. An example is presented here called OB TRAIN
      (Obstetric Triage by Resource Allocation for Inpatient). To accomplish a
      comprehensive obstetric disaster plan, there must be 1) national adoption of a
      common triage and evacuation language including an effective patient tracking
      system to avoid maternal-neonatal separation; 2) a stratification of maternity
      hospital levels of care; and 3) a collaborative network of obstetric hospitals,
      both regionally and nationally. However, obstetric disaster planning goes beyond
      evacuation and must include plans for shelter-in-place and surge capacity, all
      uniquely designed for the obstetric patient. Disasters, manmade or natural, are
      neither predictable nor preventable, but we can and should prepare for them. 

PMID- 24901272
TI  - Stillbirth risk among fetuses with ultrasound-detected isolated congenital
      anomalies.
AB  - OBJECTIVE: To estimate the risk of stillbirth among pregnancies complicated by a
      major isolated congenital anomaly detected by antenatal ultrasonography and the
      influence of incidental growth restriction. METHODS: A retrospective cohort study
      of all consecutive singleton pregnancies undergoing routine anatomic survey
      between 1990 and 2009 was performed. Stillbirth rates among fetuses with an
      ultrasound-detected isolated major congenital anomaly were compared with fetuses
      without major anomalies. Stillbirth rates were calculated per 1,000 ongoing
      pregnancies. Exclusion criteria included delivery before 24 weeks of gestation,
      multiple fetal anomalies, minor anomalies, and chromosomal abnormalities.
      Analyses were stratified by gestational age at delivery (before 32 weeks compared
      with 32 weeks of gestation or after) and birth weight less than the 10th
      percentile. We adjusted for confounders using logistic regression. RESULTS: Among
      65,308 singleton pregnancies delivered at 24 weeks of gestation or after, 873
      pregnancies with an isolated major congenital anomaly (1.3%) were identified. The
      overall stillbirth rate among fetuses with a major anomaly was 55 per 1,000
      compared with 4 per 1,000 in nonanomalous fetuses (adjusted odds ratio [OR]
      15.17, 95% confidence interval [CI] 11.03-20.86). Stillbirth risk in anomalous
      fetuses was similar before 32 weeks of gestation (26/1,000) and 32 weeks of
      gestation or after (31/1,000). Among growth-restricted fetuses, the stillbirth
      rate increased among anomalous (127/1,000) and nonanomalous fetuses (18/1,000),
      and congenital anomalies remained associated with higher rates of stillbirth
      (adjusted OR 8.20, 95% CI 5.27-12.74). CONCLUSION: The stillbirth rate is
      increased in anomalous fetuses regardless of incidental growth restriction. These
      risks can assist practitioners in designing care plans for anomalous fetuses who
      have elevated and competing risks of stillbirth and neonatal death. LEVEL OF
      EVIDENCE: II.

PMID- 24901274
TI  - Influence of shift work on early reproductive outcomes: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To determine whether an association exists between shift work and
      early reproductive outcomes. DATA SOURCES: MEDLINE, Embase, and Web of Science
      were searched. Additional sources included Google Scholar, the Cochrane Library,
      online publications of national colleges, the ClinicalTrials.gov, and references
      of retrieved papers. METHODS OF STUDY SELECTION: Included studies compared female
      shift workers (work outside 8:00 AM to 6:00 PM) with nonshift workers with
      menstrual disruption (cycles less than 25 days or greater than 31 days),
      infertility (time-to-pregnancy exceeding 12 months), or early spontaneous
      pregnancy loss (less than 25 weeks). TABULATION, INTEGRATION, AND RESULTS: Two
      reviewers extracted adjusted and raw data. Random effect models were used to pool
      data weighting for the inverse of variance. Assessments of heterogeneity, bias,
      and subgroup analyses were performed. Sixteen independent cohorts from 15 studies
      (123,403 women) were subject to analysis. Shift workers had increased rates of
      menstrual disruption (16.05% [2,207/13,749] compared with 13.05% [7,561/57,932]
      [n=71.681, odds ratio {OR} 1.22, 95% confidence interval {CI} 1.15-1.29, I 0%])
      and infertility (11.3% [529/4,668] compared with 9.9% [2,354/23,811] [OR 1.80,
      95% CI 1.01-3.20, I 94%]) but not early spontaneous pregnancy loss (11.84%
      [939/7,931] compared with 12.11% [1,898/15,673] [n=23,604, OR 0.96, 95% CI 0.88
      1.05, I 0%]). Night shifts were associated with increased early spontaneous
      pregnancy loss (n=13,018, OR 1.29, 95% CI 1.11-1.50, I 0%). Confounder adjustment
      led to persistent relationships between shift work and menstrual disruption
      (adjusted OR 1.15, 95% CI 1.01-1.31, I 70%) but not infertility (adjusted OR 1.11
      95% CI 0.86-1.44, I 61%). The association between night shifts and early
      spontaneous pregnancy loss remained (adjusted OR 1.41 95% CI 1.22-1.63, I 0%).
      CONCLUSION: This review provides evidence for an association between performing
      shift work and early reproductive outcomes, consistent with later pregnancy
      findings. However, there is currently insufficient evidence for clinicians to
      advise restricting shift work in women of reproductive age.

PMID- 24901275
TI  - Optimizing Women's Health Care Resources.

PMID- 24901276
TI  - A revised birth weight reference for the United States.
AB  - OBJECTIVE: To generate birth weight curves based on the obstetric estimate of
      gestational age as specified in the revised 2003 U.S. birth certificate. METHODS:
      Using National Center for Health Statistics data from 2011, we constructed birth
      weight curves for neonates between 24 and 42 weeks of gestation. Curves were
      developed using the obstetric estimate of gestational age that is included in the
      revised 2003 U.S. birth certificate, which, when available, incorporates
      ultrasound dating information. Live-born singleton neonates between 500 and 6,000
      g without malformations were included. These curves were compared with curves we
      generated using 1991 data on which the current national reference of Alexander
      and colleagues is based, a reference that used only last menstrual period to
      establish gestational age. RESULTS: The 1991 curves were based on 3,684,778 U.S.
      live births and the 2011 on 3,252,011 births. Birth weight percentile values were
      greater from 28 to 36 weeks of gestation in the 1991 data set. That is, the birth
      weights for preterm neonates were overestimated when 1991 reference curves were
      used compared with the proposed 2011 reference. For example, in 1991, a birth
      weight of 2,000 g was at the 50th percentile between 31 and 32 weeks of
      gestation, whereas in 2011, a birth weight of 2,000 g now corresponds to the 50th
      percentile between 33 and 34 weeks of gestation. CONCLUSIONS: Our revised
      reference curve for the United States provides an updated national reference for
      birth weight. LEVEL OF EVIDENCE: : II.

PMID- 24901277
TI  - Targeted thyroid testing during pregnancy in clinical practice.
AB  - OBJECTIVE: To evaluate the efficacy of a targeted thyroid testing approach during
      pregnancy in clinical practice. METHODS: This is a retrospective cohort study
      performed within Uppsala County, Sweden. Data were derived from the population
      based Uppsala Biobank of Pregnant Women, in which blood samples are collected in
      conjunction with the routine ultrasound screening in gestational week 17-19. For
      this study, 5,254 pregnant women with an estimated date of delivery between
      January 1, 2009, and December 31, 2011, were included. On review of their medical
      records, women who were tested for thyroid dysfunction during pregnancy in
      clinical practice were identified (n=891). From the remaining untested women,
      1,006 women were randomly selected for analyses of thyrotropin (TSH), free
      thyroxine levels, and thyroid peroxidase antibodies. Thyroid-stimulating hormone
      levels in both groups were analyzed with regard to trimester-specific upper
      reference levels as recommended by the International Endocrine Society
      Guidelines. RESULTS: The proportion of trimester-specific TSH elevation was 12.6%
      in the targeted thyroid testing group and 12.1% in the untested group (P=.8; odds
      ratio [OR] 1.04, 95% confidence interval [CI] 0.79-1.37). The proportion of overt
      hypothyroidism was 1.1% and 0.7% in the groups, respectively (P=.4; OR 1.57, 95%
      CI 0.55-4.45). CONCLUSIONS: The prevalence of trimester-specific elevated TSH and
      overt hypothyroidism was equal in targeted thyroid tested and untested women.
      When implemented in clinical practice, targeted thyroid testing is
      unsatisfactory. If ongoing studies provide support for treatment of pregnant
      women with elevated TSH, universal thyroid testing appears the most reasonable
      approach. LEVEL OF EVIDENCE: : II.

PMID- 24901278
TI  - An organization for academic specialists: the time has come.
AB  - The Society for Academic Specialists in General Obstetrics and Gynecology was
      recently formed to meet the professional needs of general obstetrician
      gynecologists (ob-gyns) in academic settings. Historically there has been little
      communication and poor networking among this group, largely as a result of lack
      of infrastructure. Until the Society for Academic Specialists in General
      Obstetrics and Gynecology, there has been no common venue to unite academic
      specialists nor a means to identify colleagues and develop professional
      relationships. The Society is creating avenues for communication and
      collaboration among general ob-gyn faculty across institutions. The Society for
      Academic Specialists in General Obstetrics and Gynecology is hosting national
      meetings, conducting workshops and webinars, and developing other media to
      promote research training, share administrative skills, and help members to
      become more effective educators. One major focus of the new organization is to
      provide resources to facilitate faculty development. Formation of the Society for
      Academic Specialists in General Obstetrics and Gynecology is particularly timely
      given that ob-gyns, without subspecialty fellowship training, have assumed major
      roles in academic departments. Their contribution to educational, scholarly, and
      clinical responsibilities is a significant benefit to the well-being of the
      departments of obstetrics and gynecology. In turn, the role of educator and
      scholar is of value to the general academic ob-gyn. The Society for Academic
      Specialists in General Obstetrics and Gynecology will help academic faculty and
      their institutions by filling current gaps in professional and career
      development, which should improve scholarship, enhance retention, and improve the
      ability for academic departments to fulfill their educational and clinical
      missions. 

PMID- 24901280
TI  - The American Congress of Obstetricians and Gynecologists and the American Medical
      Association: common ground makes common sense.

PMID- 24901279
TI  - Version of breech fetuses by moxibustion with acupuncture: a randomized
      controlled trial.
AB  - OBJECTIVE: To assess the efficacy of moxibustion (heating of the acupuncture
      needle with an igniting charcoal moxa stick) with acupuncture for version of
      breech presentations after 33 4/7 weeks of gestation to reduce their rate at 37
      weeks of gestation and at delivery. METHODS: This was a randomized placebo
      controlled single-blind trial including 328 pregnant women recruited in a
      university hospital center between 33 4/7 and 35 4/7 weeks of gestation.
      Moxibustion with acupuncture or inactivated laser (placebo) treatment was applied
      to point BL 67 for six sessions. The principal endpoint was the percentage of
      fetuses in breech presentation at 37 2/7 weeks of gestation. RESULTS: The study
      included 328 women randomized into two groups: moxibustion with acupuncture
      (n=164) or placebo (n=164). The percentage of fetuses in breech presentation at
      37 2/7 weeks of gestation was not significantly different in both groups (72.0 in
      the moxibustion with acupuncture group compared with 63.4% in the placebo group,
      relative risk 1.13, 95% confidence interval 0.98-1.32, P=.10). CONCLUSION:
      Treatment by moxibustion with acupuncture was not effective in correcting breech
      presentation in the third trimester of pregnancy. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT01487590.

PMID- 24901281
TI  - Maternal prepregnancy folate intake and risk of spontaneous abortion and
      stillbirth.
AB  - OBJECTIVE: To evaluate prospectively the relationship between prepregnancy folate
      intake and risk of spontaneous abortion and stillbirth. METHODS: Women in the
      Nurses' Health Study II who self-reported a pregnancy between 1992 and 2009 were
      included in this analysis. Dietary folate and supplement use was assessed every 4
      years, starting in 1991, by a food frequency questionnaire. Pregnancies were self
      reported with case pregnancies lost spontaneously (spontaneous abortion less than
      20 weeks of gestation and stillbirth 20+ weeks of gestation) and comparison
      pregnancies ending in ectopic pregnancy, induced abortion, or live birth.
      RESULTS: Among the 11,072 women, 15,950 pregnancies were reported of which 2,756
      (17.3%) ended in spontaneous abortion and 120 (0.8%) ended in stillbirth.
      Compared with women in the lowest quintile of prepregnancy folate intake (less
      than 285 micrograms/d), those in the highest quintile (greater than 851
      micrograms/d) had a relative risk of spontaneous abortion of 0.91 (95% confidence
      interval [CI] 0.82-1.02) after multivariable adjustment (P trend=.04). This
      association was primarily attributable to intake of folate from supplements.
      Compared with women without supplemental folate intake (0 micrograms/d), those in
      the highest category (greater than 730 micrograms/d) had a relative risk of
      spontaneous abortion of 0.80 (95% CI 0.71-0.90) after multivariable adjustment (P
      trend <.001). The association of prepregnancy supplemental folate with risk of
      spontaneous abortion was consistent across gestational period of loss. A similar
      inverse trend was observed with the risk of stillbirth, which fell short of
      conventional significance (P trend=.06). CONCLUSIONS: Higher intake of folate
      from supplements was associated with reduced risk of spontaneous abortion. Women
      at risk of pregnancy should use supplemental folate for neural tube defect
      prevention and because it may decrease the risk of spontaneous abortion. LEVEL OF
      EVIDENCE: : II.

PMID- 24901282
TI  - What is new in abnormal uterine bleeding? Best articles from the past year.

PMID- 24901284
TI  - The debate on thyroid screening during pregnancy continues.

PMID- 24901283
TI  - Information for readers and authors.

PMID- 24901285
TI  - Likelihood of continued childbearing after cesarean delivery in the United
      States.
AB  - OBJECTIVE: To estimate the likelihood of continued childbearing as a function of
      mode of delivery and number of cesarean deliveries and to explore whether it
      varies by sociodemographic characteristics. METHODS: Cross-sectional data from
      the 2006-2010 National Survey of Family Growth were used to conduct an analysis
      of U.S. childbearing women. The birth trajectory for respondents who identified a
      live, singleton, first birth was assessed through four births. Population
      weighted analyses were performed to test the association between route of
      delivery and sociodemographic characteristics with the likelihood of subsequent
      birth. RESULTS: Among 6,526 respondents, cesarean delivery, regardless of birth
      order, was associated with a lower likelihood of future birth, which decreased in
      a dose-response fashion as the number of cesarean deliveries increased. Among
      women with three births, those with two or three cesarean deliveries were 37% and
      59% less likely (P<.05), respectively, to have a fourth birth when compared with
      women with three vaginal deliveries, adjusting for confounders. When interaction
      terms were added to the model, lower income women were significantly more likely
      to have a fourth birth after undergoing two or three cesarean deliveries than
      women with higher incomes (adjusted incidence rate ratio 2.50, 95% confidence
      interval [CI] 1.23-5.05 and adjusted incidence rate ratio 2.39, 95% CI 1.01-5.65,
      respectively). CONCLUSIONS: U.S. women who have cesarean deliveries are less
      likely to continue childbearing, especially because they undergo higher numbers
      of cesarean deliveries; however, this relationship is attenuated among low-income
      women. Given the risks associated with multiple cesarean deliveries, these
      findings underscore the need to further examine this relationship and what
      factors may be driving the income-based difference in childbearing after cesarean
      deliveries. LEVEL OF EVIDENCE: II.

PMID- 24901286
TI  - Surface plasmon resonance in gold ultrathin nanorods and nanowires.
AB  - We synthesized and measured optical extinction spectra of Au ultrathin (diameter:
      ~1.6 nm) nanowires (UNWs) and nanorods (UNRs) with controlled lengths in the
      range 20-400 nm. The Au UNWs and UNRs exhibited a broad band in the IR region
      whose peak position was red-shifted with the length. Polarized extinction
      spectroscopy for the aligned Au UNWs indicated that the IR band is assigned to
      the longitudinal mode of the surface plasmon resonance. 

PMID- 24901287
TI  - A microtensiometer capable of measuring water potentials below -10 MPa.
AB  - Tensiometers sense the chemical potential of water (or water potential, Psiw) in
      an external phase of interest by measuring the pressure in an internal volume of
      liquid water in equilibrium with that phase. For sub-saturated phases, the
      internal pressure is below atmospheric and frequently negative; the liquid is
      under tension. Here, we present the initial characterization of a new tensiometer
      based on a microelectromechanical pressure sensor and a nanoporous membrane. We
      explain the mechanism of operation, fabrication, and calibration of this device.
      We show that these microtensiometers operate stably out to water potentials below
      -10 MPa, a tenfold extension of the range of current tensiometers. Finally, we
      present use of the device to perform an accurate measurement of the equation of
      state of liquid water at pressures down to -14 MPa. We conclude with a discussion
      of outstanding design considerations, and of the opportunities opened by the
      extended range of stability and the small form factor in sensing applications,
      and in fundamental studies of the thermodynamic properties of water. 

PMID- 24901288
TI  - Just-in-time training of dental responders in a simulated pandemic immunization
      response exercise.
AB  - ABSTRACT OBJECTIVE: The reauthorization of the Pandemic and All-Hazards
      Preparedness Act in 2013 incorporated the dental profession and dental
      professionals into the federal legislation governing public health response to
      pandemics and all-hazard situations. Work is now necessary to expand the
      processes needed to incorporate and train oral health care professionals into
      pandemic and all-hazard response events. METHODS: A just-in-time (JIT) training
      exercise and immunization drill using an ex vivo porcine model system was
      conducted to demonstrate the rapidity to which dental professionals can respond
      to a pandemic influenza scenario. Medical history documentation, vaccination
      procedures, and patient throughput and error rates of 15 dental responders were
      evaluated by trained nursing staff and emergency response personnel. RESULTS: The
      average throughput (22.33/hr) and medical error rates (7 of 335; 2.08%) of the
      dental responders were similar to those found in analogous influenza mass
      vaccination clinics previously conducted using certified public health nurses.
      CONCLUSIONS: The dental responder immunization drill validated the capacity and
      capability of dental professionals to function as a valuable immunization
      resource. The ex vivo porcine model system used for JIT training can serve as a
      simple and inexpensive training tool to update pandemic responders' immunization
      techniques and procedures supporting inoculation protocols.

PMID- 24901289
TI  - [Antipsychotic use in the cohort PACA-Alz in patients with Alzheimer's disease
      and other dementia in 2010].
AB  - AIM: The aim of the study was to identify and to characterize patients with
      Alzheimer's disease or related dementia describing antipsychotics and other
      psychotropic expositions. METHODS: The study was performed, in 2010, based on
      Provence-Alpes-Cote d'Azur region (PACA)-Corse Alz cohort included patients with
      dementia, with chronic condition 'Alzheimer disease or related disease' and/or
      had at least one delivery of Alzheimer's specific treatment, registered in the
      General Health Care System. Psychotropic drugs were extracted according
      anatomical, therapeutical and chemical code. Chronic exposure defined as more
      than 3 consecutive deliveries. RESULTS: Among 34 696 included patients, 26.9%
      were men and 68.8% were 80 years old and more. Among them, 26% received at least
      one antipsychotic medication, with a chronic exposition estimated around 61.3%.
      Antidepressant and anxiolytic were consumed respectively by 47% and 45.3% of
      patients. Risperidone was the most used antipsychotic (11.2%). The Health care
      use (hospitalizations, nurses and physicians visits) was significantly higher
      among patients with antipsychotics. CONCLUSION: Antipsychotics use in patients
      with dementia remains high. The follow up of this regional cohort would be
      helpful to identify the impact of guidelines on the prescription and the care of
      patients with dementia.

PMID- 24901290
TI  - Vitamin K1 antagonisation is not safe in high thromboembolic risk patients with
      over-anticoagulation.
AB  - We report a case of a fatal massive anterior acute myocardial infarction (AMI)
      after administration of vitamin K1 for over-anticoagulation following
      cardioembolism from mechanical mitroaortic valve prostheses associated with
      atrial fibrillation. 

PMID- 24901291
TI  - [Use of oral drugs and short bowel syndrome: an analysis of practices].
AB  - OBJECTIVE: To describe drug prescription patterns in patients with short bowel
      syndrome (SBS). METHODS: The drug prescriptions of patients suffering from SBS
      type 1 to 3 were compared. RESULTS: Seventy-nine percent of the drugs were
      prescribed by oral route, and this proportion was significantly higher in
      patients with type 3 compared to tose with type 1. Twenty-nine percent of
      prescriptions were dietary supplement-drugs, 14.3% were gastrointestinal drugs
      and 11.4% were cardiovascular drugs. Oral prescription medications for SBS
      concerned many drug categories. The number of gastrointestinal or dietary
      supplement drugs was comparable between the 3 types. Drug doses were not
      increased compared with the recommendations, except for gastrointestinal drugs.
      CONCLUSION: The oral administration is common and at usual dosage in patients
      with SBS despite a lack of studies on absorption that may help to individualize
      drug prescription.

PMID- 24901293
TI  - Energy transfer from a single semiconductor nanocrystal to dye molecules.
AB  - In an energy transfer (ET) process, it is the optical responses of donor and
      acceptor materials on the single-particle level that ultimately determine its
      overall performance. Here we conduct time-tagged, time-resolved optical
      measurements to correlate the photoluminescence (PL) intensities and lifetimes of
      a donor semiconductor nanocrystal (NC) and acceptor dye molecules linked to its
      surface. We reveal that the PL intensity of dye molecules follows exactly the
      blinking behavior of the donor NC and shows a step-like quenching behavior due to
      the photobleaching effect. The corresponding recovery of the NC PL intensity has
      allowed us to realize the textbook definition of PL quantum efficiency
      measurement in dye molecules upon absorbing a single exciton. Our theoretical
      fitting of the lifetime data demonstrates that the buildup time of acceptor PL
      could be solely determined by the radiative lifetime of dye molecules when it is
      any shorter than the NC lifetime, thus confirming the long-existing Forster
      theory on ET dynamics.

PMID- 24901292
TI  - A 16-year prospective study of community-onset bacteremic Acinetobacter
      pneumonia: low mortality with appropriate initial empirical antibiotic protocols.
AB  - BACKGROUND: The genus Acinetobacter, well known as a nosocomial pathogen, can
      also cause severe community-onset pneumonia. Previous small case series have
      suggested fulminant disease and a pooled hospital mortality of > 60%. METHODS: We
      conducted a prospective observational study of all episodes of bacteremic,
      community-onset, and radiologically confirmed pneumonia due to Acinetobacter
      species at a tertiary referral hospital in tropical Australia from 1997 to 2012
      following the introduction of routine empirical treatment protocols covering
      Acinetobacter. Demographic, clinical, microbiologic, and outcome data were
      collected. RESULTS: There were 41 episodes of bacteremic community-onset
      Acinetobacter pneumonia, of which 36 had no indicators suggesting health-care
      associated infection. Of these, 38 (93%) were Indigenous Australians, one-half
      were men, the average age was 44.1 years, and 36 episodes (88%) occurred during
      the rainy season. All patients had at least one risk factor, with hazardous
      alcohol intake in 82%. Of the 37 isolates available for molecular speciation, 35
      were Acinetobacter baumannii and two were Acinetobacter nosocomialis. All
      isolates were susceptible in vitro to gentamicin, meropenem, and ciprofloxacin,
      but only one was fully susceptible to ceftriaxone. ICU admission was required in
      80%. All 41 patients received appropriate antibiotics within the first 24 h of
      admission, and 28- and 90-day mortality were both low at 11%. CONCLUSIONS:
      Community-acquired Acinetobacter pneumonia is a severe disease, with the majority
      of patients requiring ICU admission. Most patients have risk factors,
      particularly hazardous alcohol use. Despite this severity, correct initial
      empirical antibiotic therapy in all patients was associated with low mortality.

PMID- 24901295
TI  - Total synthesis of lacosamide.
AB  - Total synthesis of anticonvulsant amino acid, lacosamide, is reported. The key
      step is stereospecific allyl cyanate-to-isocyanate rearrangement, which proceeds
      with chirality transfer. The enantiopure starting material for the rearrangement
      step was accessed from ethyl L-lactate.

PMID- 24901294
TI  - Following drug uptake and reactions inside Escherichia coli cells by Raman
      microspectroscopy.
AB  - Raman microspectroscopy combined with Raman difference spectroscopy reveals the
      details of chemical reactions within bacterial cells. The method provides direct
      quantitative data on penetration of druglike molecules into Escherichia coli
      cells in situ along with the details of drug-target reactions. With this label
      free technique, clavulanic acid and tazobactam can be observed as they penetrate
      into E. coli cells and subsequently inhibit beta-lactamase enzymes produced
      within these cells. When E. coli cells contain a beta-lactamase that forms a
      stable complex with an inhibitor, the Raman signature of the known enamine acyl
      enzyme complex is detected. From Raman intensities it is facile to measure
      semiquantitatively the number of clavulanic acid molecules taken up by the
      lactamase-free cells during growth. 

PMID- 24901296
TI  - Characterization of Acinetobacter baumannii clinical isolates carrying bla(OXA
      23) carbapenemase and 16S rRNA methylase armA genes in Yemen.
AB  - PURPOSE: The aim of this study was to investigate the molecular support of
      resistance to carbapenems, aminoglycosides, and fluoroquinolones in Acinetobacter
      baumannii clinical isolates collected from Yemen hospital. METHODS: Three A.
      baumannii were isolated in February 2013 from three patients hospitalized at Al
      Thawra University Hospital in Sana'a, Yemen. Antibiotic susceptibility testing
      was performed using the disk diffusion and E-test methods. Carbapenemase
      production was carried out by the modified Hodge test (MHT) and imipenem
      ethylenediaminetetraacetic acid (EDTA) methods. Carbapenem, aminoglycoside, and
      fluoroquinolone resistance determinants were studied by polymerase chain reaction
      and sequencing. The epidemiological relatedness of the three strains was studied
      using multilocus sequence typing (MLST). RESULTS: The isolates were resistant to
      almost all antibiotics tested with very high imipenem, amikacin, and
      ciprofloxacin minimum inhibitory concentrations (>32, >256, and >32 mg/L,
      respectively). The microbiological tests showed that the three A. baumannii were
      MHT positive, besides, the activity of beta-lactamases was not inhibited by EDTA.
      All the three isolates contained the naturally occurring bla(OXA-51)-like gene
      and the bla(OXA-23)-like carbapenemase-encoding gene. The 16S rRNA methylase armA
      gene was detected in the three isolates. In addition, screening for genes
      encoding the aminoglycoside-modifying enzymes (AMEs) demonstrated that one
      isolate contained the acetyltransferase gene aac(6')-Ib. Fluoroquinolone
      resistance was associated with a single mutation Ser83Leu in the quinolone
      resistance determining region of the gyrA gene in all isolates. The MLST showed
      that the sequence type (ST) obtained corresponds to ST2 for the three strains.
      CONCLUSIONS: Here we report the first identification of multidrug-resistant A.
      baumannii isolates harboring the bla(OXA-23)-like gene, AMEs [aac(6')-Ib], and
      the 16S rRNA methylase (armA) in the Yemen hospital.

PMID- 24901297
TI  - Organizational climate and employee mental health outcomes: A systematic review
      of studies in health care organizations.
AB  - BACKGROUND: In recent years, the high prevalence of mental health problems among
      health care workers has given rise to great concern. The academic literature
      suggests that employees' perceptions of their work environment can play a role in
      explaining mental health outcomes. PURPOSES: We conducted a systematic review of
      the literature in order to answer the following two research questions: (1) how
      does organizational climate relate to mental health outcomes among employees
      working in health care organizations and (2) which organizational climate
      dimension is most strongly related to mental health outcomes among employees
      working in health care organizations? METHODOLOGY/APPROACH: Four search
      strategies plus inclusion and quality assessment criteria were applied to
      identify and select eligible studies. As a result, 21 studies were included in
      the review. Data were extracted from the studies to create a findings database.
      The contents of the studies were analyzed and categorized according to common
      characteristics. FINDINGS: Perceptions of a good organizational climate were
      significantly associated with positive employee mental health outcomes such as
      lower levels of burnout, depression, and anxiety. More specifically, our findings
      indicate that group relationships between coworkers are very important in
      explaining the mental health of health care workers. There is also evidence that
      aspects of leadership and supervision affect mental health outcomes.
      Relationships between communication, or participation, and mental health outcomes
      were less clear. PRACTICAL IMPLICATIONS: If health care organizations want to
      address mental health issues among their staff, our findings suggest that
      organizations will benefit from incorporating organizational climate factors in
      their health and safety policies. Stimulating a supportive atmosphere among
      coworkers and developing relationship-oriented leadership styles would seem to be
      steps in the right direction.

PMID- 24901298
TI  - Promoting retention of nurses: A meta-analytic examination of causes of nurse
      turnover.
AB  - BACKGROUND: Because the health care field is expected to be the fastest growing
      job field until 2020, an urgent need to focus on nurse retention exists. PURPOSE:
      The aim of this study was to examine the relationships between predictors of
      turnover (i.e., personal characteristics, role states, job characteristics,
      group/leader relations, organizational/environmental perceptions, attitudinal
      reactions) and turnover cognitions and intentions, as well as actual turnover
      among nurses, in an effort to determine the strongest predictors of voluntary
      turnover. METHODOLOGY: Meta-analysis was used to determine best estimates of the
      effect of predictors on turnover based on 106 primary studies of employed nurses.
      Meta-analyzed correlations were subjected to path analysis to establish the
      structural relationships among the study variables. FINDINGS: Supportive and
      communicative leadership, network centrality, and organizational commitment are
      the strongest predictors of voluntary turnover based on meta-analytic
      correlations. Additional variables that relate to nurse turnover intentions
      include job strain, role tension, work-family conflict, job control, job
      complexity, rewards/recognition, and team cohesion. PRACTICE IMPLICATIONS: The
      findings suggest that some factors, such as salary, are relatively less important
      in prediction of turnover. Administrators concerned about nurse turnover may more
      effectively direct resources toward altering certain job characteristics and work
      conditions in the effort to reduce voluntary turnover among nurses.

PMID- 24901299
TI  - Breaking the silence: Determinants of voice for quality improvement in hospitals.
AB  - BACKGROUND: Research suggests that staff voice-discretionary communication of
      ideas, suggestions, concerns, or opinions about work-related issues with the
      intent to improve organizational or unit functioning-is associated with quality
      improvement, which most agree is needed in health care. Nevertheless, health
      professionals often do not voice. Little research has explored their reluctance
      to speak up and, relatedly, the conditions under which they voice. PURPOSE: We
      examine the drivers of voice for health professionals in hospitals. Specifically,
      we investigate the factors that influence their voice, why these factors are
      influential, and the purposes for which staff use their voice. METHODOLOGY: We
      conducted a qualitative study using data from 99 in-depth interviews with diverse
      staff at 12 randomly sampled hospitals in the United States. Data were collected
      from December 2007 to December 2008, the first year of a 4-year study of
      improvement. By national standards, all of the hospitals had significant room for
      improvement in their care of patients experiencing heart attack, suggesting that
      there were potentially issues and suggestions for staff to voice. FINDINGS:
      Factors related to individuals (e.g., tenure), work (e.g., work configuration),
      organizational context (e.g., culture), data (e.g., benchmarking), and the
      external environment (e.g., attention) influenced health professionals' voice.
      These factors shaped their sense of safety, efficacy, opportunity, and/or
      legitimacy, all of which affected their belief about the risk and benefit of
      voice and willingness to voice. They voiced for three purposes: to learn for
      themselves, inform others, and protect patients. PRACTICE IMPLICATIONS: These
      findings indicate that hospitals and their leaders must attend to multiple
      factors (e.g., work configuration, culture, etc.) if they wish to increase staff
      voice in service of quality improvement. The presence of many influential factors
      suggests that there are several levers that leaders can use to elicit voice,
      noting that voice can be used in multiple ways to facilitate improvement.

PMID- 24901300
TI  - Development of an ultraperformance liquid chromatography-tandem mass spectrometry
      method for the analysis of perfluorinated compounds in fish and Fatty food.
AB  - This paper reports the development of a method for the quantitative analysis of
      perfluorinated compounds (PFCs), including C6-C14 perfluorinated carboxylic acids
      (PFCAs) and C4-C12 perfluorinated sulfonates (PFSAs), in fish and fatty foods by
      ultraperformance liquid chromatography-electrospray ionization-tandem mass
      spectrometry (UPLC-ESI-MS/MS) in which the UPLC was equipped a PFC Analysis Kit
      to eliminate background contamination. Rapid baseline separation was achieved for
      17 PFCs within 12 min, and PFCs were well-resolved from potential interferences
      from taurodeoxycholic acid and branched isomers of PFCs. The method was validated
      according to Commission Regulation 2002/657/EC of the European Commission with
      matrices including salmon, beef, egg, and butter. Average spiked recoveries,
      measured at concentration levels of 0.02 (method limit of quantification (MLOQ)),
      0.2, and 2 MUg/kg, were in the range of 68-117% with relative standard deviations
      below 20%. Matrix effects were evaluated and found to be correctable by internal
      standardization, especially for short- and long-chained PFCs. Trueness was
      verified against two certified reference materials. The method has also been
      successfully applied to the analysis of more than 200 food samples of a risk
      assessment study. 

PMID- 24901302
TI  - Diastereomeric control of enantioselectivity: evidence for metal cluster
      catalysis.
AB  - Enantioselective hydrogenation of tiglic acid effected by diastereomers of the
      general formula [(MU-H)2Ru3(MU3-S)(CO)7(MU-P-P*)] (P-P* = chiral Walphos
      diphosphine ligand) strongly supports catalysis by intact Ru3 clusters. A
      catalytic mechanism involving Ru3 clusters has been established by DFT
      calculations. 

PMID- 24901304
TI  - Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome
      Stability and Prevention of Carcinogenesis.
AB  - The fragile FHIT gene, encompassing the chromosomal fragile site FRA3B, is an
      early target of DNA damage in precancerous cells. While vulnerable to DNA damage
      itself, FHIT protein expression is essential to protect from DNA damage-induced
      cancer initiation and progression by modulating genome stability, oxidative
      stress and levels of accumulating DNA damage. Thus, FHIT, whose expression is
      lost or reduced in many human cancers, is a tumor suppressor and genome caretaker
      whose loss initiates genome instability in preneoplastic lesions. Ongoing studies
      are seeking more detailed understanding of the role of FHIT in the cellular
      response to oxidative damage. This review discusses the relationship between
      FHIT, reactive oxygen species production, and DNA damage in the context of cancer
      initiation and progression. 

PMID- 24901305
TI  - Effect of carbohydrate or sodium bicarbonate ingestion on performance during a
      validated basketball simulation test.
AB  - Current recommendations for nutritional interventions in basketball are largely
      extrapolated from laboratory-based studies that are not sport-specific. We
      therefore adapted and validated a basketball simulation test relative to
      competitive basketball games using well-trained basketball players (n = 10), then
      employed this test to evaluate the effects of two common preexercise nutritional
      interventions on basketball-specific physical and skilled performance.
      Specifically, in a randomized and counterbalanced order, participants ingested
      solutions providing either 75 g carbohydrate (sucrose) 45 min before exercise
      (Study A; n = 10) or 2 * 0.2 g . kg(-1) sodium bicarbonate (NaHCO3) 90 and 20 min
      before exercise (Study B; n = 7), each relative to appropriate placebos (H2O and
      2 * 0.14 g . kg(-1) NaCl, respectively). Heart rate, sweat rate, pedometer count,
      and perceived exertion did not systematically differ between the 60-min
      basketball simulation test and competitive basketball, with a strong positive
      correlation in heart rate response (r = .9, p < .001). Preexercise carbohydrate
      ingestion resulted in marked hypoglycemia (< 3.5 mmol . l(-1)) throughout the
      first quarter, coincident with impaired sprinting (+0.08 +/- 0.05 second; p =
      .01) and layup shooting performance (8.5/11 versus 10.3/11 baskets; p < .01).
      However, ingestion of either carbohydrate or sodium bicarbonate before exercise
      offset fatigue such that sprinting performance was maintained into the final
      quarter relative to placebo (Study A: -0.07 +/- 0.04 second; p < .01 and Study B:
      -0.08 +/- 0.05 second; p = .02), although neither translated into improved
      skilled (layup shooting) performance. This basketball simulation test provides a
      valid reflection of physiological demands in competitive basketball and is
      sufficiently sensitive to detect meaningful changes in physical and skilled
      performance. While there are benefits of preexercise carbohydrate or sodium
      bicarbonate ingestion, these should be balanced against potential negative side
      effects.

PMID- 24901306
TI  - The NOD-like receptor signalling pathway in Helicobacter pylori infection and
      related gastric cancer: a case-control study and gene expression analyses.
AB  - BACKGROUND: Currently, it is well established that cancer arises in chronically
      inflamed tissue. A number of NOD-like receptors (NLRs) form inflammasomes,
      intracellular multiprotein complexes critical for generating mature pro
      inflammatory cytokines (IL-1beta and IL-18). As chronic inflammation of the
      gastric mucosa is a consequence of Helicobacter pylori infection, we investigated
      the role of genetic polymorphisms and expression of genes involved in the NLR
      signalling pathway in H. pylori infection and related gastric cancer (GC).
      MATERIALS AND METHODS: Fifty-one genetic polymorphisms were genotyped in 310
      ethnic Chinese (87 non-cardia GC cases and 223 controls with functional
      dyspepsia). In addition, gene expression of 84 molecules involved in the NLR
      signalling pathway was assessed in THP-1 cells challenged with two H. pylori
      strains, GC026 (GC) and 26695 (gastritis). RESULTS: CARD8-rs11672725, NLRP3
      rs10754558, NLRP3-rs4612666, NLRP12-rs199475867 and NLRX1-rs10790286 showed
      significant associations with GC. On multivariate analysis, CARD8-rs11672725
      remained a risk factor (OR: 4.80, 95% CI: 1.39-16.58). Further, NLRP12-rs2866112
      increased the risk of H. pylori infection (OR: 2.13, 95% CI: 1.22-3.71).
      Statistical analyses assessing the joint effect of H. pylori infection and the
      selected polymorphisms revealed strong associations with GC (CARD8, NLRP3, CASP1
      and NLRP12 polymorphisms). In gene expression analyses, five genes encoding NLRs
      were significantly regulated in H. pylori-challenged cells (NLRC4, NLRC5, NLRP9,
      NLRP12 and NLRX1). Interestingly, persistent up-regulation of NFKB1 with
      simultaneous down-regulation of NLRP12 and NLRX1 was observed in H. pylori GC026
      challenged cells. Further, NF-kappaB target genes encoding pro-inflammatory
      cytokines, chemokines and molecules involved in carcinogenesis were markedly up
      regulated in H. pylori GC026-challenged cells. CONCLUSIONS: Novel associations
      between polymorphisms in the NLR signalling pathway (CARD8, NLRP3, NLRP12, NLRX1,
      and CASP1) and GC were identified in Chinese individuals. Our genetic
      polymorphisms and gene expression results highlight the relevance of the NLR
      signalling pathway in gastric carcinogenesis and its close interaction with NF
      kappaB.

PMID- 24901307
TI  - Factors affecting perceived stigma in leprosy affected persons in western Nepal.
AB  - BACKGROUND: There are various factors which construct the perception of stigma in
      both leprosy affected persons and unaffected persons. The main purpose of this
      study was to determine the level of perceived stigma and the risk factors
      contributing to it among leprosy affected person attending the Green Pastures
      Hospital, Pokhara municipality of western Nepal. METHODS: A cross-sectional study
      was conducted among 135 people affected by leprosy at Green Pastures Hospital and
      Rehabilitation Centre. Persons above the age of 18 were interviewed using a set
      of questionnaire form and Explanatory Model Interview Catalogue (EMIC). In
      addition, two sets of focused group discussions each containing 10 participants
      from the ward were conducted with the objectives of answering the frequently
      affected EMIC items. RESULTS: Among 135 leprosy affected persons, the median
      score of perceived stigma was 10 while it ranged from 0-34. Higher perceived
      stigma score was found in illiterate persons (p=0.008), participants whose
      incomes were self-described as inadequate (p=0.014) and who had changed their
      occupation due to leprosy (p=0.018). Patients who lacked information on leprosy
      (p=0.025), knowledge about the causes (p=0.02) and transmission of leprosy
      (p=0.046) and those who had perception that leprosy is a severe disease (p<0.001)
      and is difficult to treat (p<0.001) had higher perceived stigma score.
      Participants with disfigurement or deformities (p=0.014), ulcers (p=0.022) and
      odorous ulcers (p=0.043) had higher perceived stigma score. CONCLUSION: The
      factors associated with higher stigma were illiteracy, perceived economical
      inadequacy, change of occupation due to leprosy, lack of knowledge about leprosy,
      perception of leprosy as a severe disease and difficult to treat. Similarly,
      visible deformities and ulcers were associated with higher stigma. There is an
      urgent need of stigma reduction strategies focused on health education and health
      awareness programs in addition to the necessary rehabilitation support.

PMID- 24901308
TI  - The effects of codon context on in vivo translation speed.
AB  - We developed a bacterial genetic system based on translation of the his operon
      leader peptide gene to determine the relative speed at which the ribosome reads
      single or multiple codons in vivo. Low frequency effects of so-called "silent"
      codon changes and codon neighbor (context) effects could be measured using this
      assay. An advantage of this system is that translation speed is unaffected by the
      primary sequence of the His leader peptide. We show that the apparent speed at
      which ribosomes translate synonymous codons can vary substantially even for
      synonymous codons read by the same tRNA species. Assaying translation through
      codon pairs for the 5'- and 3'- side positioning of the 64 codons relative to a
      specific codon revealed that the codon-pair orientation significantly affected in
      vivo translation speed. Codon pairs with rare arginine codons and successive
      proline codons were among the slowest codon pairs translated in vivo. This system
      allowed us to determine the effects of different factors on in vivo translation
      speed including Shine-Dalgarno sequence, rate of dipeptide bond formation, codon
      context, and charged tRNA levels. 

PMID- 24901310
TI  - Dietary patterns and whole grain cereals in the Scandinavian countries-
      differences and similarities. The HELGA project.
AB  - OBJECTIVE: To identify dietary patterns with whole grains as a main focus to see
      if there is a similar whole grain pattern in the three Scandinavian countries;
      Denmark, Sweden and Norway. Another objective is to see if items suggested for a
      Nordic Food Index will form a typical Nordic pattern when using factor analysis.
      SETTING: The HELGA study population is based on samples of existing cohorts: the
      Norwegian Women and Cancer Study, the Swedish Vasterbotten cohort and the Danish
      Diet, Cancer and Health study. The HELGA study aims to generate knowledge about
      the health effects of whole grain foods. SUBJECTS: The study included a total of
      119 913 participants. DESIGN: The associations among food variables from FFQ were
      investigated by principal component analysis. Only food groups common for all
      three cohorts were included. High factor loading of a food item shows high
      correlation of the item to the specific diet pattern. RESULTS: The main whole
      grain for Denmark and Sweden was rye, while Norway had highest consumption of
      wheat. Three similar patterns were found: a cereal pattern, a meat pattern and a
      bread pattern. However, even if the patterns look similar, the food items
      belonging to the patterns differ between countries. CONCLUSIONS: High loadings on
      breakfast cereals and whole grain oat were common in the cereal patterns for all
      three countries. Thus, the cereal pattern may be considered a common Scandinavian
      whole grain pattern. Food items belonging to a Nordic Food Index were distributed
      between different patterns.

PMID- 24901311
TI  - Reconstructive surgery of the sulcus of glans penis for balanopreputial adhesion
      due to lichen sclerosus. Our experience and medicolegal implications.
AB  - AIM: Our exeperience with the reconstructive surgery of the adhesion of the glans
      with the preputial skin due to lichen sclerosus. MATERIAL OF STUDY: Twentyeight
      patients (mean age, 44 years; range, 28-69) underwent reshaping of the
      balanopreputial sulcus at our institution. All patients presented with trapped
      penis resulting from adhesion at the sulcus of glans due to Lichen Sclerosus. The
      procedure entailed separating the coronal adhesion along its entire length with
      the use of a blunttipped forceps, then reshaping the balanopreputial sulcus.
      Though simple, the maneuver is delicate and requires scrupulous attention to the
      ventral aspect to avoid damaging the urethra. The adhesion is removed
      circumferentially around the glans by means of electrobistoury. RESULTS: The
      duration of the follow-up period was 24 months. All patients stated they were
      satisfied with the cosmetic results and functional outcome. Recurrence of the
      condition occurred in 7% of the patients and was treated medically; recurrence of
      adhesion occurred in 2% of the patients and was treated with repeat surgery.
      DISCUSSION: The indication for medical therapy in early LS is a selective
      criterion restricted to less severe cases; otherwise, the physician may be held
      responsible for treatment failure, justified claims for reimbursement, disease
      progression and the decidedly greater damage that may ensue. Such consequences
      can be averted when assessment is based on recent scientific evidence and the
      approach to treatment is appropriate in terms of efficacy and effectiveness.
      Surgical management is definitive and restores normal penile anatomy and
      function, including sexual and urinary function, thus enabling the patient to
      regain sexual confidence CONCLUSIONS: Lichen sclerosus et atrophicus is a rare
      disease, however, its management is not devoid of medicolegal considerations. The
      etiopathogenesis of the disease is unknown but progression to carcinoma of the
      penis has been reported in untreated cases. Consequently, timely diagnosis holds
      medicolegal relevance for averting delayed initiation of treatment. In cases of
      balanopreputial adhesion with disappearance of the sulcus of glans, we proceed
      with lysis and reshaping of the sulcus by means of a simple technique we have
      developed. The technique involves separating the coronal adhesion
      circumferentially around the glans using a blunt-tipped forceps, then reshaping
      the balanopreputial sulcus. Though very simple, the procedure is also delicate as
      the surgeon must be careful not to damage the urethra beneath the ventral
      surface.

PMID- 24901309
TI  - Nutrient patterns and their food sources in an International Study Setting:
      report from the EPIC study.
AB  - BACKGROUND: Compared to food patterns, nutrient patterns have been rarely used
      particularly at international level. We studied, in the context of a multi-center
      study with heterogeneous data, the methodological challenges regarding pattern
      analyses. METHODOLOGY/PRINCIPAL FINDINGS: We identified nutrient patterns from
      food frequency questionnaires (FFQ) in the European Prospective Investigation
      into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR)
      data to validate and describe the nutrient patterns and their related food
      sources. Associations between lifestyle factors and the nutrient patterns were
      also examined. Principal component analysis (PCA) was applied on 23 nutrients
      derived from country-specific FFQ combining data from all EPIC centers (N =
      477,312). Harmonized 24-HDRs available for a representative sample of the EPIC
      populations (N = 34,436) provided accurate mean group estimates of nutrients and
      foods by quintiles of pattern scores, presented graphically. An overall PCA
      combining all data captured a good proportion of the variance explained in each
      EPIC center. Four nutrient patterns were identified explaining 67% of the total
      variance: Principle component (PC) 1 was characterized by a high contribution of
      nutrients from plant food sources and a low contribution of nutrients from animal
      food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was
      characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized
      by calcium, proteins, riboflavin, and phosphorus. The nutrients with high
      loadings on a particular pattern as derived from country-specific FFQ also showed
      high deviations in their mean EPIC intakes by quintiles of pattern scores when
      estimated from 24-HDR. Center and energy intake explained most of the variability
      in pattern scores. CONCLUSION/SIGNIFICANCE: The use of 24-HDR enabled internal
      validation and facilitated the interpretation of the nutrient patterns derived
      from FFQs in term of food sources. These outcomes open research opportunities and
      perspectives of using nutrient patterns in future studies particularly at
      international level.

PMID- 24901312
TI  - Calcium channel blockers for inhibiting preterm labour and birth.
AB  - BACKGROUND: Preterm birth is a major contributor to perinatal mortality and
      morbidity, affecting around 9% of births in high-income countries and an
      estimated 13% of births in low- and middle-income countries. Tocolytics are drugs
      used to suppress uterine contractions for women in preterm labour. The most
      widely used tocolytic are the betamimetics, however, these are associated with a
      high frequency of unpleasant and sometimes severe maternal side effects. Calcium
      channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy
      with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs)
      (e.g. atosiban) also have a low side-effect profile. OBJECTIVES: To assess the
      effects on maternal, fetal and neonatal outcomes of CCBs, administered as a
      tocolytic agent, to women in preterm labour. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013).
      SELECTION CRITERIA: All published and unpublished randomised trials in which CCBs
      were used for tocolysis for women in labour between 20 and 36 completed weeks'
      gestation. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial eligibility, undertook quality assessment and data extraction.
      Results are presented using risk ratio (RR) for categorical data and mean
      difference (MD) for data measured on a continuous scale with the 95% confidence
      interval (CI). The number needed to treat to benefit (NNTB) and the number needed
      to treat to harm (NNTH) were calculated for categorical outcomes that were
      statistically significantly different. MAIN RESULTS: This update includes 26
      additional trials involving 2511 women, giving a total of 38 included trials
      (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used
      nicardipine. Blinding of intervention and outcome assessment was undertaken in
      only one of the trials (a placebo controlled trial). However, objective outcomes
      defined according to timing of birth and perinatal mortality were considered to
      have low risk of detection bias.Two small trials comparing CCBs with placebo or
      no treatment showed a significant reduction in birth less than 48 hours after
      trial entry (RR 0.30, 95% CI 0.21 to 0.43) and an increase in maternal adverse
      effects (RR 49.89, 95% CI 3.13 to 795.02, one trial of 89 women). Due to
      substantial heterogeneity, outcome data for preterm birth (less than 37 weeks)
      were not combined; one placebo controlled trial showed no difference (RR 0.96,
      95% CI 0.89 to 1.03) while the other (non-placebo controlled trial) reported a
      reduction (RR 0.44, 95% CI 0.31 to 0.62). No other outcomes were
      reported.Comparing CCBs (mainly nifedipine) with other tocolytics by type
      (including betamimetics, glyceryl trinitrate (GTN) patch, non-steriodal anti
      inflammatories (NSAID), magnesium sulphate and ORAs), no significant reductions
      were shown in primary outcome measures of birth within 48 hours of treatment or
      perinatal mortality.Comparing CCBs with betamimetics, there were fewer maternal
      adverse effects (average RR 0.36, 95% CI 0.24 to 0.53) and fewer maternal adverse
      effects requiring discontinuation of therapy (average RR 0.22, 95% CI 0.10 to
      0.48). Calcium channel blockers resulted in an increase in the interval between
      trial entry and birth (average MD 4.38 days, 95% CI 0.25 to 8.52) and gestational
      age (MD 0.71 weeks, 95% CI 0.34 to 1.09), while decreasing preterm and very
      preterm birth (RR 0.89, 95% CI 0.80 to 0.98 and RR 0.78, 95% CI 0.66 to 0.93);
      respiratory distress syndrome (RR 0.64, 95% CI 0.48 to 0.86); necrotising
      enterocolitis (RR 0.21, 95% CI 0.05 to 0.96); intraventricular haemorrhage (RR
      0.53, 95% CI 0.34 to 0.84); neonatal jaundice (RR 0.72, 95% CI 0.57 to 0.92); and
      admissions to neonatal intensive care unit (NICU) (average RR 0.74, 95% CI 0.63
      to 0.87). No difference was shown in one trial of outcomes at nine to twelve
      years of age.Comparing CCBs with ORA, data from one study (which did blind the
      intervention) showed an increase in gestational age at birth (MD 1.20 completed
      weeks, 95% CI 0.25 to 2.15) and reductions in preterm birth (RR 0.64, 95% CI 0.47
      to 0.89); admissions to the NICU (RR 0.59, 95% CI 0.41 to 0.85); and duration of
      stay in the NICU (MD -5.40 days,95% CI -10.84 to 0.04). Maternal adverse effects
      were increased in the CCB group (average RR 2.61, 95% CI 1.43 to 4.74).Comparing
      CCBs with magnesium sulphate, maternal adverse effects were reduced (average RR
      0.52, 95% CI 0.40 to 0.68), as was duration of stay in the NICU (days) (MD -4.55,
      95% CI -8.17 to -0.92). No differences were shown in the comparisons with GTN
      patch or NSAID, although numbers were small.No differences in outcomes were shown
      in trials comparing nicardipine with other tocolytics, although with limited data
      no strong conclusions can be drawn. No differences were evident in a small trial
      that compared higher- versus lower-dose nifedipine, though findings tended to
      favour a high dose on some measures of neonatal morbidity. AUTHORS' CONCLUSIONS:
      Calcium channel blockers (mainly nifedipine) for women in preterm labour have
      benefits over placebo or no treatment in terms of postponement of birth thus,
      theoretically, allowing time for administration of antenatal corticosteroids and
      transfer to higher level care. Calcium channel blockers were shown to have
      benefits over betamimetics with respect to prolongation of pregnancy, serious
      neonatal morbidity, and maternal adverse effects. Calcium channel blockers may
      also have some benefits over ORAs and magnesium sulphate, although ORAs results
      in fewer maternal adverse effects. However, it must be noted that no difference
      was shown in perinatal mortality, and data on longer-term outcomes were limited.
      Further, the lack of blinding of the intervention diminishes the strength of this
      body of evidence. Further well-designed tocolytic trials are required to
      determine short- and longer-term infant benefit of CCBs over placebo or no
      treatment and other tocolytics, particularly ORAs. Another important focus for
      future trials is identifying optimal dosage regimens of different types of CCBs
      (high versus low, particularly addressing speed of onset of uterine quiescence)
      and formulation (capsules versus tablets). All future trials on tocolytics for
      women in preterm labour should employ blinding of the intervention and outcome
      assessment, include measurement of longer-term effects into early childhood, and
      also costs.

PMID- 24901313
TI  - [What should we eat?].

PMID- 24901314
TI  - [Glucocorticoids in neurology: mechanism of action, applications and side
      effects].
AB  - Glucocorticoids represent a cornerstone in the therapy for many neurological
      disorders. Even though their mechanism of action is still not completely
      understood, synthetic glucocorticoids are given as first line drugs in a number
      of immunological and non-immunological disorders of the central or peripheral
      nervous system. For most of these disorders, however, the level of evidence that
      glucocorticoids are truly effective is still not sufficient. This is why
      treatment with glucocorticoids cannot be recommended on an evidenced-based level
      for many of these disorders. Due to the huge number of acute or chronic side
      effects, it is essential that the effects are documented by more randomised
      placebo-controlled cross-over trials. Generally, glucocorticoids can no longer be
      omitted in the treatment of neurological disorders, the indication to apply
      glucocorticoids, however, needs to be thoroughly balanced in the light of their
      many side effects.

PMID- 24901315
TI  - [Satellite systems of the basal ganglia--anatomic position, clinical relevance].
AB  - The interaction of basal ganglia and other brain regions is more complex
      regarding anatomic and functional perspectives than previously assumed. Hence,
      the classical basal ganglia model has to be extended to at least four satellite
      systems modulating motor-executive, associative and limbic-motivational brain
      regions: (i) an indirect projection system, (ii) a striato-nigro-striatal loop,
      (iii) a "hyperdirect" projection system as well as additional projections to the
      subthalamic nucleus and (iv) multisynaptic connections from the cerebellum
      exerting influence on the indirect projection system. The investigation of these
      satellite systems would be invaluable to foster our understanding of basal
      ganglia circuitries and may yield a better appreciation of largely opaque
      symptoms like resting tremor in Parkinson's disease; analysis of these anatomic
      pathways and functional implications may facilitate explanatory model approaches
      to side effects due to dopaminergic therapy and deep brain stimulation in humans
      and thereby offer the possibility for new therapeutic approaches in movement
      disorders.

PMID- 24901316
TI  - [Animal hoarding: a mental disorder with implications for public health].
AB  - Animal hoarding (AH) is a mental disorder that is characterised by an excessive
      number of kept animals, inability to maintain minimal standards of animal care
      and hygiene, and deficient insight into the thereby developing failures and
      problems. Although AH as a disease concept is neither represented in the DSM-5
      nor the ICD-10, it may be classified as a subform of the hoarding disorder (DSM-5
      300.3) that was implemented in the DSM-5 as an obsessive-compulsive disorder. Due
      to the hygienic deficiencies of the living spaces and the insufficient keeping of
      animals there is an increased risk of epizootic diseases and zoonoses. Specific
      epidemiological studies do not exist, however, women seem to be affected more
      frequently. AH is diagnosed mostly in late adulthood. Besides thorough somatic
      and psychiatric medical diagnostics, cooperation with the veterinary offices and
      authorities is usually necessary. Comorbid mental disorders (particularly
      depressive, obsessive-compulsive and personality disorders) are frequent.
      Currently, no evidence-based therapies exist. Social therapy and cognitive
      behavioural psychotherapeutic interventions as well as sufficient treatment of
      comorbid mental disorders are recommended.

PMID- 24901317
TI  - [Adult ADHD versus borderline personality disorder: criteria for differential
      diagnosis].
AB  - The present study focuses on selected symptom criteria to distinguish between
      attention deficit/hyperactivity disorder (ADHD) in adults and borderline
      personality disorder (BPD). A sample of n = 158 subjects was examined, consisting
      of BPD patients (n = 37), ADHD patients (n = 58), comorbid BPD/ADHD patients (n =
      19), a clinical group of patients fulfilling the diagnostic criteria of a
      depressive disorder (DEP; n = 22) and a non-clinical control group (KG; n = 22).
      Selected symptom criteria were investigated by using the German scales "Skala zur
      Erfassung der Impulsivitat und emotionalen Dysregulation der Borderline
      Personlichkeitsstorung" (IES-27), "ADHS-Screening fur Erwachsene" (ADHS-LE),
      "Fragebogen zu dissoziativen Symptomen" (FDS) and a scale for the assessment of
      paranoid and dichotomous thinking (PADI). Multivariate analyses of variance
      revealed that BPD patients differed significantly with respect to self-mutilating
      behaviour, suicidality, dissociation, paranoia and dichotomy from all other
      groups. The same effect was found for affect regulation. Furthermore BPD patients
      differed significantly from ADHD patients by a more severe impulsiveness (IES
      27), but not through disturbed impulse control and disinhibition overall.
      Regarding mean differences between ADHD and BPD patients for attentional control,
      ADHD patients revealed higher scores which just missed significance. For
      hyperactivity no significant group differences were found which is assumed to be
      influenced by symptom overlap like restlessness and aversive tension. The
      findings suggest that BPD-specific criteria, a stronger affective dysregulation
      and a higher tendency for autoaggressive impulsive reactions are more selective
      for differential diagnosis than the core symptoms of adult ADHD. Only attentional
      control might be a useful criterion for differential diagnosis, which should be
      examined in future studies.

PMID- 24901318
TI  - [Long-term treatment of bipolar disorder].

PMID- 24901319
TI  - Luteolin inhibits behavioral sensitization by blocking methamphetamine-induced
      MAPK pathway activation in the caudate putamen in mice.
AB  - GOAL: To investigate the effect of luteolin on methamphetamine (MA)-induced
      behavioral sensitization and mitogen-activated protein kinase (MAPK) signal
      transduction pathway activation in mice. METHODS: Mice received a single dose of
      MA to induce hyperactivity or repeated intermittent intraperitoneal injections of
      MA to establish an MA-induced behavioral sensitization mouse model. The effect of
      luteolin on the development and expression of MA-induced hyperactivity and
      behavioral sensitization was examined. The expression and activity of DeltaFosB
      and the levels of phosphorylated extracellular signal-regulated kinase 1/2
      (pERK1/2), phosphorylated c-Jun N-terminal kinase (pJNK), and phosphorylated p38
      mitogen-activated protein kinase (pp38) in the caudate putamen (CPu) were
      measured by western blot. RESULTS: Luteolin significantly decreased hyperactivity
      as well as the development and expression of MA-induced behavioral sensitization
      in mice. DeltaFosB, pERK1/2, and pJNK levels in the CPu were higher in MA-treated
      mice than in control mice, whereas the pp38 level did not change. Injection of
      luteolin inhibited the MA-induced increase in DeltaFosB, pERK1/2, and pJNK
      levels, but did not affect the pp38 level. CONCLUSIONS: Luteolin inhibits MA
      induced hyperactivity and behavioral sensitization in mice through the
      ERK1/2/DeltaFosB pathway. Furthermore, the JNK signaling pathway might be
      involved in MA-induced neurodegeneration in the CPu, and luteolin inhibits this
      process.

PMID- 24901320
TI  - BM-1197: a novel and specific Bcl-2/Bcl-xL inhibitor inducing complete and long
      lasting tumor regression in vivo.
AB  - Bcl-2 and Bcl-xL are critical regulators of apoptosis that are overexpressed in a
      variety of human cancers and pharmacological inhibition of Bcl-2 and Bcl-xL
      represents a promising strategy for cancer treatment. Using a structure-based
      design approach, we have designed BM-1197 as a potent and efficacious dual
      inhibitor of Bcl-2 and Bcl-xL. BM-1197 binds to Bcl-2 and Bcl-xL proteins with Ki
      values less than 1 nM and shows >1,000-fold selectivity over Mcl-1. Mechanistic
      studies performed in the Mcl-1 knockout mouse embryonic fibroblast (MEF) cells
      revealed that BM-1197 potently disassociates the heterodimeric interactions
      between anti-apoptotic and pro-apoptotic Bcl-2 family proteins, concomitant with
      conformational changes in Bax protein, loss of mitochondrial membrane potential
      and subsequent cytochrome c release to the cytosol, leading to activation of the
      caspase cascade and apoptosis. BM-1197 exerts potent growth-inhibitory activity
      in 7 of 12 small cell lung cancer cell lines tested and induces mechanism-based
      apoptotic cell death. When intravenously administered at daily or weekly in H146
      and H1963 small-cell lung cancer xenograft models, it achieves complete and long
      term tumor regression. Consistent with its targeting of Bcl-xL, BM-1197 causes
      transit platelet reduction in mice. Collectively, our data indicate that BM-1197
      is a promising dual Bcl-2/Bcl-xL inhibitor which warrants further investigation
      as a new anticancer drug. 

PMID- 24901322
TI  - New method for automatic body length measurement of the collembolan, Folsomia
      candida Willem 1902 (Insecta: Collembola).
AB  - The collembolan, Folsomia candida, is widely used in soil ecotoxicology. In
      recent years, growth rate of collembolans has become as frequently used endpoint
      as reproduction rate in ecotoxicological studies. However, measuring collembolan
      body sizes to estimate growth rate is a complicated and time-consuming task. Here
      we present a new image analysis method, which facilitates and accelerates the
      body length measurement of the collembolan Folsomia candida. The new software
      package, called CollScope, consists of three elements: 1) an imaging device; 2)
      photographing software; 3) an ImageJ macro for image processing, measurement and
      data analysis. We give a complete description of the operation of the software,
      the image analyzing process and describe its accuracy and reliability. The
      software with a detailed usage manual is attached as Supplementary Material. We
      report a case study to demonstrate that the automated measurement of collembolan
      body sizes is highly correlated with the traditional manual measurements
      (estimated measuring accuracy 0.05 mm). Furthermore, we performed a dose-response
      ecotoxicity test using cadmium-sulfate by using CollScope as well as classical
      methods for size measurement. Size data measured by CollScope or manually did not
      differ significantly. Furthermore the new software package decreased time
      consumption of the measurements to 42% when tested on 35 animals. Consequently,
      methodological investigations performed in this study should be regarded as a
      recommendation for any other routine dose-response study where body growth is an
      endpoint. 

PMID- 24901321
TI  - Interactome profile of the host cellular proteins and the nonstructural protein 2
      of porcine reproductive and respiratory syndrome virus.
AB  - The nonstructural protein 2 (NSP2) is considered to be one of crucial viral
      proteins in the replication and pathogenesis of porcine reproductive and
      respiratory syndrome virus (PRRSV). In the present study, the host cellular
      proteins that interact with the NSP2 of PRRSV were immunoprecipitated with anti
      Myc antibody from the MARC-145 cells infected by a recombinant PRRSV with 3xMyc
      tag insertion in its NSP2-coding region, and then 285 cellular proteins
      interacting with NSP2 were identified by LC-MS/MS. The Gene Ontology and enriched
      KEGG Pathway bioinformatics analyses indicated that the identified proteins could
      be assigned to different subcellular locations and functional classes. Functional
      analysis of the interactome profile highlighted cellular pathways associated with
      infectious disease, translation, immune system, nervous system and signal
      transduction. Two interested cellular proteins-BCL2-associated athanogene 6
      (BAG6) and apoptosis-inducing factor 1 (AIF1) which may involve in transporting
      of NSP2 to Endoplasmic reticulum (ER) or PRRSV-driven apoptosis were validated by
      Western blot. The interactome data between PRRSV NSP2 and cellular proteins
      contribute to the understanding of the roles of NSP2 in the replication and
      pathogenesis of PRRSV, and also provide novel cellular target proteins for
      elucidating the associated molecular mechanisms of the interaction of host
      cellular proteins with viral proteins in regulating the viral replication. 

PMID- 24901323
TI  - Associations between care pathways and outcome 1 year after severe traumatic
      brain injury.
AB  - OBJECTIVE: To assess associations between real-world care pathways for working
      age patients in the first year after severe traumatic brain injury and outcomes
      at 1 year. SETTING AND DESIGN: Prospective, observational study with recruitment
      from 6 neurosurgical centers in Sweden and Iceland. Follow-up to 1 year,
      independently of care pathways, by rehabilitation physicians and paramedical
      professionals. PARTICIPANTS: Patients with severe traumatic brain injury, lowest
      (nonsedated) Glasgow Coma Scale score 3 to 8 during the first 24 hours and
      requiring neurosurgical intensive care, age 18 to 65 years, and alive 3 weeks
      after injury. MAIN MEASURES: Length of stay in intensive care, time between
      intensive care discharge and rehabilitation admission, outcome at 1 year (Glasgow
      Outcome Scale Extended score), acute markers of injury severity, preexisting
      medical conditions, and post-acute complications. Logistic regression analyses
      were performed. RESULTS: A multivariate model found variables significantly
      associated with outcome (odds ratio for good outcome [confidence interval], P
      value) to be as follows: length of stay in intensive care (0.92 [0.87-0.98],
      0.014), time between intensive care discharge and admission to inpatient
      rehabilitation (0.97 [0.94-0.99], 0.017), and post-acute complications (0.058
      [0.006-0.60], 0.017). CONCLUSIONS: Delays in rehabilitation admission were
      negatively associated with outcome. Measures to ensure timely rehabilitation
      admission may improve outcome. Further research is needed to evaluate possible
      causation.

PMID- 24901324
TI  - Does mechanism of injury play a role in recovery from concussion?
AB  - BACKGROUND: High school football and soccer are 2 of the leading causes of
      concussion injuries. However, concussions also occur from mechanisms of injury
      such as motor vehicle accidents (MVAs), assault, and work-related accidents.
      PURPOSE: Determine if recovery from concussion could be related to the mechanism
      of injury. SETTING: Berkshire Medical Center Concussion Clinic. PARTICIPANTS:
      Patients aged 13 to 21 years suffering concussion from football (n = 31), soccer
      (n = 9), or MVAs (n = 20). OUTCOME MEASUREMENTS: ImPACT (Immediate Post
      Concussion Assessment Tool) test scores including symptom inventory; number of
      days sick; length of time to recovery. RESULTS: Most commonly reported symptom at
      the time of injury was headache. Patients were seen in clinic an average of 16
      (football), 14 (soccer), and 21 (MVA) days postinjury. Groups differed
      significantly on ImPACT Visual Memory and Visual Motor Speed scores (P < .05).
      MVA patients had a longer median number of days sick (97 days) than football
      players (32 days; P < .05). CONCLUSION: This study suggests that concussion from
      an MVA may be a more serious injury than a typical concussion sustained during
      sports. Data suggest that MVA patients take longer to present to clinic, have
      lower Visual Memory and Visual Motor Speed scores on ImPACT, and take longer to
      recover. Further studies are needed to better understand how the mechanism of
      injury of concussion may relate to prognosis.

PMID- 24901325
TI  - Traumatic brain injury and psychogenic seizures in veterans.
AB  - OBJECTIVE: To evaluate a proposed seizure etiology of traumatic brain injury
      (TBI) as a risk factor for psychogenic nonepileptic seizures (PNESs), the effect
      of reported TBI severity on the diagnosis of PNES versus epileptic seizures
      (ESs), and the potential moderating role of posttraumatic stress disorder (PTSD).
      PARTICIPANTS, SETTING: Veterans with a diagnosis of PNES or ES during epilepsy
      monitoring at a Veterans Affairs Medical Center. DESIGN: Retrospective review of
      seizure type, proposed seizure etiology, TBI severity, and PTSD. MAIN OUTCOMES:
      Both PNES and ES groups were compared for TBI history and severity, and prior
      diagnosis of PTSD. RESULTS: Traumatic brain injury was the proposed seizure
      etiology for 57% of 67 PNES patients versus 35% of 54 ES patients (P < .05). It
      was mild in 87% of PNES patients and 37% of ES patients (P < .001). Posttraumatic
      stress disorder increased the likelihood of diagnosing PNES versus ES in Veterans
      with mild TBI as the proposed seizure etiology. CONCLUSIONS: Veterans with PNES
      commonly cite a TBI as the cause for seizures. Mild TBI was strongly associated
      with PNES versus ES. Posttraumatic stress disorder may moderate the development
      of PNES in Veterans with a history of mild TBI. Clinicians caring for Veterans
      with seizures may use these results in selecting patients for early diagnostic
      evaluation.

PMID- 24901326
TI  - Prevalence differences of patients in vegetative state in The Netherlands and
      Vienna, Austria: a comparison of values and ethics.
AB  - OBJECTIVE: Little is known about prevalence of persistent vegetative
      state/unresponsive wakefulness syndrome and comparisons between countries. The
      aim of this column was to explore reasons for the comparable count of patients in
      vegetative state found in prevalence studies in nursing homes in 1 European
      country (Netherlands) compared with a single European city (Vienna, Austria).
      DESIGN: The column is based on a literature review of vegetative state in The
      Netherlands and Vienna in the period 2007-2008, in the context of professional
      interactions with families and physicians of patients in vegetative state. In
      addition, in both countries, families and physicians were interviewed to
      illustrate views. RESULTS: Comparable between the 2 settings are the population
      characteristics and the definition of, and criteria, for vegetative state. A
      difference can be found in the development of authoritative policy guidelines in
      the Netherlands, after public debates and jurisdiction, which did not exist in
      Vienna at the time. There also seem to be different societal values concerning
      rehabilitation and end-of-life decisions for patients in vegetative state.
      DISCUSSION: The most important explanation for the vegetative state prevalence
      differences between the Netherlands and Vienna can be found in the different
      societal values about patients in vegetative state and their treatment and
      rehabilitation. In the Netherlands, life prolonging medical treatment, including
      artificial nutrition and hydration, is considered futile and can be withdrawn if
      there is no prospect of recovery. In Vienna, however, patients in vegetative
      state are regarded as severely disabled and in need of long-term rehabilitation
      and social reintegration. There is no end-of-life discussion in this context.

PMID- 24901327
TI  - Relation of repeated low-level blast exposure with symptomology similar to
      concussion.
AB  - OBJECTIVE: To investigate anecdotal reports suggesting that repeated exposure to
      low-level explosive blast has myriad health impacts, including an array of
      neurological effects. PARTICIPANTS: A total of 184 anonymous survey respondents
      from military and nonmilitary law enforcement populations (135 exposed to
      occupational blast and 49 controls). DESIGN: Survey of self-reported history of
      occupational exposure to repeated low-level blast (breaching blast) and
      symptomology similar to concussion. RESULTS: Findings suggest that number and
      severity of symptoms increase with history of chronic blast exposure (F = 18.26,
      P < .001) and that symptoms can interfere with daily activity (t = 2.60, P =
      .010). CONCLUSION: Given the prevalence of repeated exposure to blast among some
      military and civilian law enforcement occupations, the results of this survey
      study support a role for blast surveillance programs as well as continued
      research on health impacts of low-level repeated blast exposure.

PMID- 24901328
TI  - Selective Cognitive Dysfunction Is Related to a Specific Pattern of Cerebral
      Damage in Persons With Severe Traumatic Brain Injury.
AB  - OBJECTIVE: Cognitive dysfunction is a common sequela of traumatic brain injury
      (TBI); indeed, patients show a heterogeneous pattern of cognitive deficits. This
      study was aimed at investigating whether patients who show selective cognitive
      dysfunction after TBI present a selective pattern of cerebral damage. SETTING:
      Post-Coma Unit, IRCCS Santa Lucia Foundation, Rome, Italy. PARTICIPANTS: We
      collected data from 8 TBI patients with episodic memory disorder and without
      executive deficits, 7 patients with executive function impairment and preserved
      episodic memory capacities, and 16 healthy controls. DESIGN: We used 2
      complementary analyses: (1) an exploratory and qualitative approach in which we
      investigated the distribution of lesions in the TBI groups, and (2) a hypothesis
      driven and quantitative approach in which we calculated the volume of hippocampi
      of individuals in the TBI and control groups. MAIN MEASURES: Neuropsychological
      scores and hippocampal volumes. RESULTS: We found that patients with TBI and
      executive functions impairment presented focal lesions involving the frontal
      lobes, whereas patients with TBI and episodic memory disorders showed atrophic
      changes of the mesial temporal structure (hippocampus). CONCLUSION: The
      complexity of TBI is due to several heterogeneous factors. Indeed, studying
      patients with TBI and selective cognitive dysfunction should lead to a better
      understanding of correlations with specific brain impairment and damage, better
      follow-up of long-term outcome scenarios, and better planning of selective and
      focused rehabilitation programs.

PMID- 24901329
TI  - Chronic Inflammation After Severe Traumatic Brain Injury: Characterization and
      Associations With Outcome at 6 and 12 Months Postinjury.
AB  - OBJECTIVE: Examine associations between chronic inflammatory profiles and outcome
      6 to 12 months following severe traumatic brain injury (TBI). SETTING: University
      affiliated level 1 trauma center and community. PARTICIPANTS: Adults with severe
      TBI (n = 87); healthy controls (n = 7). DESIGN: Prospective cohort study. MAIN
      MEASURES: Glasgow Outcome Scale; serum cytokines (interleukin [IL]-1beta, IL-4,
      IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor alpha), 2 weeks to 3
      months, 4- to 6-month averages, 6- and 12-month levels. RESULTS: Serum levels of
      IL-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor alpha were elevated over 3
      months following TBI. Multivariate analysis showed that increased cytokine load
      score was associated with a 1.21 (95% confidence interval, 1.06-1.38) and 1.18
      (95% confidence interval, 1.02-1.37) increase in odds of unfavorable Glasgow
      Outcome Scale score at 6 and 12 months, respectively. Also, elevated IL-6/IL-10
      ratios were associated with increased odds of unfavorable outcomes at 6 months
      (adjusted odds ratio = 1.76; 95% confidence interval, 1.08-2.88). CONCLUSIONS:
      Chronic inflammation has not been well characterized following TBI. Our subacute
      cytokine load score classifies individuals at risk for unfavorable outcomes
      following injury. Higher proinflammatory burden with IL-6, relative to the anti
      inflammatory marker IL-10, is significantly associated with outcome. Further
      research should examine whether inflammatory genes and other inflammatory
      biomarkers affect risk for unfavorable outcomes and TBI complications.

PMID- 24901331
TI  - Multidimensional compressed sensing MRI using tensor decomposition-based
      sparsifying transform.
AB  - Compressed Sensing (CS) has been applied in dynamic Magnetic Resonance Imaging
      (MRI) to accelerate the data acquisition without noticeably degrading the spatial
      temporal resolution. A suitable sparsity basis is one of the key components to
      successful CS applications. Conventionally, a multidimensional dataset in dynamic
      MRI is treated as a series of two-dimensional matrices, and then various
      matrix/vector transforms are used to explore the image sparsity. Traditional
      methods typically sparsify the spatial and temporal information independently. In
      this work, we propose a novel concept of tensor sparsity for the application of
      CS in dynamic MRI, and present the Higher-order Singular Value Decomposition
      (HOSVD) as a practical example. Applications presented in the three- and four
      dimensional MRI data demonstrate that HOSVD simultaneously exploited the
      correlations within spatial and temporal dimensions. Validations based on cardiac
      datasets indicate that the proposed method achieved comparable reconstruction
      accuracy with the low-rank matrix recovery methods and, outperformed the
      conventional sparse recovery methods. 

PMID- 24901330
TI  - Improved Cardiorespiratory Fitness With Aerobic Exercise Training in Individuals
      With Traumatic Brain Injury.
AB  - OBJECTIVE: To examine cardiorespiratory fitness in individuals with traumatic
      brain injury (TBI), before and following participation in a supervised 12-week
      aerobic exercise training program. METHODS: Ten subjects with nonpenetrating TBI
      (TBI severity: mild, 50%; moderate, 40%; severe, 10%; time since injury [mean +/-
      SD]: 6.6 +/- 6.8 years) performed exercise training on a treadmill 3 times a week
      for 30 minutes at vigorous intensity (70%-80% of heart rate reserve). All
      subjects completed a cardiopulmonary exercise test, with pulmonary gas exchange
      measured and a questionnaire related to fatigue (Fatigue Severity Scale) at
      baseline and following exercise training. RESULTS: After training, increases (P <
      .01) in peak oxygen consumption ((Equation is included in full-text article.);
      +3.1 +/- 2.4 mL/min/kg), time to volitional fatigue (+1.4 +/- 0.8 minutes), and
      peak work rate (+59 +/- 43 W) were observed. At the anaerobic threshold,
      (Equation is included in full-text article.)(+3.6 +/- 2.1 mL/kg/min), treadmill
      time (+1.8 +/- 1.1 minutes), and work rate (+37 +/- 39 W) were higher (P < .01)
      following exercise training. Subjects also reported significantly lower (P < .05)
      Fatigue Severity Scale composite scores (-0.9 +/- 1.3) following exercise
      training. CONCLUSION: These findings suggest that individuals with TBI may
      benefit from participation in vigorous aerobic exercise training with improved
      cardiorespiratory fitness and diminished fatigue.

PMID- 24901332
TI  - Optimizing metabolite production using periodic oscillations.
AB  - Methods for improving microbial strains for metabolite production remain the
      subject of constant research. Traditionally, metabolic tuning has been mostly
      limited to knockouts or overexpression of pathway genes and regulators. In this
      paper, we establish a new method to control metabolism by inducing optimally
      tuned time-oscillations in the levels of selected clusters of enzymes, as an
      alternative strategy to increase the production of a desired metabolite. Using an
      established kinetic model of the central carbon metabolism of Escherichia coli,
      we formulate this concept as a dynamic optimization problem over an extended, but
      finite time horizon. Total production of a metabolite of interest (in this case,
      phosphoenolpyruvate, PEP) is established as the objective function and time
      varying concentrations of the cellular enzymes are used as decision variables. We
      observe that by varying, in an optimal fashion, levels of key enzymes in time,
      PEP production increases significantly compared to the unoptimized system. We
      demonstrate that oscillations can improve metabolic output in experimentally
      feasible synthetic circuits. 

PMID- 24901334
TI  - A high resolution case study of a patient with recurrent Plasmodium vivax
      infections shows that relapses were caused by meiotic siblings.
AB  - Plasmodium vivax infects a hundred million people annually and endangers 40% of
      the world's population. Unlike Plasmodium falciparum, P. vivax parasites can
      persist as a dormant stage in the liver, known as the hypnozoite, and these
      dormant forms can cause malaria relapses months or years after the initial
      mosquito bite. Here we analyze whole genome sequencing data from parasites in the
      blood of a patient who experienced consecutive P. vivax relapses over 33 months
      in a non-endemic country. By analyzing patterns of identity, read coverage, and
      the presence or absence of minor alleles in the initial polyclonal and subsequent
      monoclonal infections, we show that the parasites in the three infections are
      likely meiotic siblings. We infer that these siblings are descended from a single
      tetrad-like form that developed in the infecting mosquito midgut shortly after
      fertilization. In this natural cross we find the recombination rate for P. vivax
      to be 10 kb per centimorgan and we further observe areas of disequilibrium
      surrounding major drug resistance genes. Our data provide new strategies for
      studying multiclonal infections, which are common in all types of infectious
      diseases, and for distinguishing P. vivax relapses from reinfections in malaria
      endemic regions. This work provides a theoretical foundation for studies that aim
      to determine if new or existing drugs can provide a radical cure of P. vivax
      malaria. 

PMID- 24901333
TI  - Infection and co-infection with helminths and Plasmodium among school children in
      Cote d'Ivoire: results from a National Cross-Sectional Survey.
AB  - BACKGROUND: Helminth infection and malaria remain major causes of ill-health in
      the tropics and subtropics. There are several shared risk factors (e.g.,
      poverty), and hence, helminth infection and malaria overlap geographically and
      temporally. However, the extent and consequences of helminth-Plasmodium co
      infection at different spatial scales are poorly understood. METHODOLOGY: This
      study was conducted in 92 schools across Cote d'Ivoire during the dry season,
      from November 2011 to February 2012. School children provided blood samples for
      detection of Plasmodium infection, stool samples for diagnosis of soil
      transmitted helminth (STH) and Schistosoma mansoni infections, and urine samples
      for appraisal of Schistosoma haematobium infection. A questionnaire was
      administered to obtain demographic, socioeconomic, and behavioral data.
      Multinomial regression models were utilized to determine risk factors for STH
      Plasmodium and Schistosoma-Plasmodium co-infection. PRINCIPAL FINDINGS: Complete
      parasitological and questionnaire data were available for 5,104 children aged 5
      16 years. 26.2% of the children were infected with any helminth species, whilst
      the prevalence of Plasmodium infection was 63.3%. STH-Plasmodium co-infection was
      detected in 13.5% and Schistosoma-Plasmodium in 5.6% of the children. Multinomial
      regression analysis revealed that boys, children aged 10 years and above, and
      activities involving close contact to water were significantly and positively
      associated with STH-Plasmodium co-infection. Boys, wells as source of drinking
      water, and water contact were significantly and positively associated with
      Schistosoma-Plasmodium co-infection. Access to latrines, deworming, higher
      socioeconomic status, and living in urban settings were negatively associated
      with STH-Plasmodium co-infection; whilst use of deworming drugs and access to
      modern latrines were negatively associated with Schistosoma-Plasmodium co
      infection. CONCLUSIONS/SIGNIFICANCE: More than 60% of the school children
      surveyed were infected with Plasmodium across Cote d'Ivoire, and about one out of
      six had a helminth-Plasmodium co-infection. Our findings provide a rationale to
      combine control interventions that simultaneously aim at helminthiases and
      malaria.

PMID- 24901336
TI  - Epidemiology and prognostic factors of candidemia in cancer patients.
AB  - AIM: The study of candidemia in cancer patients has been limited. This
      retrospective study aims to investigate the epidemiologic characteristics and
      prognostic factors of candidemia among cancer patients. MATERIALS AND METHODS:
      From 2009 to 2012, cancer patients with candidemia were identified at a hospital
      in Taiwan. The medical records of all patients with bloodstream infections due to
      Candida species were retrospectively reviewed. RESULTS: During the four-year
      period, a total of 242 episodes of candidemia were identified among cancer
      patients. Half of these patients were classified as elderly (>=65 years old), and
      more than 95% of the candidemia episodes were classified as healthcare-associated
      infections. Among the 242 cancer patients with candidemia, head and neck cancer
      was the most common, followed by gastrointestinal tract and lung cancer.
      Additionally, most of the patients had variable underlying conditions, such as
      the presence of CVC (99%) or prior exposure to broad-spectrum antibiotics (93%)
      and were receiving an immunosuppressant (86%). Overall, C. albicans (n = 132,
      54.5%) was the most common pathogen, followed by C. tropicalis (n = 52, 21.5%),
      C. parapsilosis (n = 38, 15.7%), and C. glabrata (n = 29, 12.0%). Seventeen
      patients had polycandidal candidemia, and 77 patients had concomitant bacteremia.
      Approximately one-third of the patients required admission to the intensive care
      unit (ICU) or mechanical ventilation, and the overall in-hospital mortality was
      50.8%. Multivariable analysis showed that the in-hospital mortality was
      significantly associated with only the non-use of antifungal agents and acute
      respiratory failure (P<.001). CONCLUSIONS: Candidemia can develop in patients
      with both solid cancer and hematological malignancy, especially for patients with
      underlying conditions. Overall, the associated morbidity and mortality due to
      Candidemia remain high. It was also determined that the non-use of antifungal
      agents and acute respiratory failure conditions were associated with in-hospital
      mortality.

PMID- 24901337
TI  - Association between capsular serotype V and macrolide resistance in group B
      Streptococcus.

PMID- 24901338
TI  - Effect of inhaler design variables on paediatric use of dry powder inhalers.
AB  - Age appropriateness is a major concern of pulmonary delivery devices, in
      particular of dry powder inhalers (DPIs), since their performance strongly
      depends on the inspiratory flow manoeuvre of the patient. Previous research on
      the use of DPIs by children focused mostly on specific DPIs or single inspiratory
      parameters. In this study, we investigated the requirements for a paediatric DPI
      more broadly using an instrumented test inhaler. Our primary aim was to assess
      the impact of airflow resistance on children's inspiratory flow profiles.
      Additionally, we investigated children's preferences for airflow resistance and
      mouthpiece design and how these relate to what may be most suitable for them. We
      tested 98 children (aged 4.7-12.6 years), of whom 91 were able to perform one or
      more correct inhalations through the test inhaler. We recorded flow profiles at
      five airflow resistances ranging from 0.025 to 0.055 kPa0.5.min.L-1 and computed
      various inspiratory flow parameters from these recordings. A sinuscope was used
      to observe any obstructions in the oral cavity during inhalation. 256 flow
      profiles were included for analysis. We found that both airflow resistance and
      the children's characteristics affect the inspiratory parameters. Our data
      suggest that a medium-high resistance is both suitable for and well appreciated
      by children aged 5-12 years. High incidences (up to 90%) of obstructions were
      found, which may restrict the use of DPIs by children. However, an oblong
      mouthpiece that was preferred the most appeared to positively affect the
      passageway through the oral cavity. To accommodate children from the age of 5
      years onwards, a DPI should deliver a sufficiently high fine particle dose within
      an inhaled volume of 0.5 L and at a peak inspiratory flow rate of 25-40 L.min-1.
      We recommend taking these requirements into account for future paediatric inhaler
      development. 

PMID- 24901339
TI  - A single bout of resistance exercise does not promote excess postexercise energy
      expenditure in untrained young men with a family history of diabetes.
AB  - BACKGROUND: People with a family history of type 2 diabetes have lower energy
      expenditure (EE) and more obesity than those having no such family history.
      Resistance exercise (RE) may induce excess postexercise energy expenditure (EPEE)
      and reduce long-term risk for obesity in this susceptible group. PURPOSE: To
      determine the effect of RE on EPEE for 15 hr after a single exercise bout in
      healthy, untrained young men having a family history of type 2 diabetes. DESIGN:
      Seven untrained men (23 +/- 1.2 years, BMI 24 +/- 1.1) completed a 48-hr protocol
      in a whole room calorimeter. The first day served as a control day, with a
      moderate 40-min RE bout occurring on the second day. Differences in postexercise
      EE were compared with matched periods from the control day for cumulative 15-min
      intervals (up to 150 min) and 15 hr after the RE bout was completed. RESULTS: The
      most robust difference in EPEE between the experimental and control days was
      observed in the first 15-min postexercise period (M = 1.4Kcal/min; SD = 0.7; p <
      .05). No statistically significant differences in EPEE were noted beyond 90-min
      of continuous measurement. CONCLUSIONS: Young people with a family history of
      type 2 diabetes may not show EPEE after a single RE bout when observed for 15 hr
      after RE and long-term resistance training may be required to promote EPEE.

PMID- 24901340
TI  - Regional changes in cerebral blood flow oxygenation can indicate global changes
      in cerebral blood flow during coronary artery occlusion in juvenile pigs.
AB  - Near infrared spectroscopy (NIRS) is a widely employed method for assessment of
      regional cerebral oxygenation (RcStO2). RcStO2 values are expected to vary with
      changes in the relative amount of oxyhaemoglobin. The present experimental study
      aimed to assess the response of RcStO2 to controlled alterations of carotid blood
      flow (CQ). Landrace pigs were anesthetized followed by surgical preparation.
      Cyclic variations in cardiac output were accomplished by intermittently occluding
      the main stem of the left coronary artery. A flow measurement probe for assessing
      CQ was placed around the left carotid artery. One NIRS probe was placed on the
      left ipsilateral forehead to assess regional cerebral oximetry. Simultaneous
      registration of CQ and RcStO2 was conducted. There was a strong correlation for
      variation in CQ and RcStO2 signal values. Based on coherence analysis the
      fraction of power of the RcStO2 that was coherent with the CQ signal reached 0.84
      +/- 0.12 (P < 0.05) for frequencies lower than 0.1 Hz. The agreement of the
      sample-to-sample co-variation, as assessed by the Pearson correlation
      coefficient, was 0.83 +/- 0.08 (P < 0.05). One explanatory component for
      variations in cerebral oxygenation verified by NIRS should be attributed to
      variations in the cerebral blood flow. 

PMID- 24901341
TI  - Non-contact assessment of COD and turbidity concentrations in water using diffuse
      reflectance UV-Vis spectroscopy.
AB  - Water contamination is an important environmental concern underlining the need
      for reliable real-time information on contaminant concentrations in natural
      waters. Here, a new non-contact UV-Vis spectroscopic approach for monitoring
      contaminants in water, and especially wastewater, is proposed. Diffuse
      reflectance UV-Vis spectroscopy was applied to measure simultaneously the
      chemical oxygen demand (COD) and turbidity (TUR) concentrations in water. The
      measurements were carried out in the wavelength range from 200-1100 nm. The
      measured spectra were analysed using partial-least-squares (PLS) regression. The
      correlation coefficient between the measured and the reference concentrations of
      COD and TUR in the water samples were R(2) = 0.85 and 0.96, respectively. These
      results highlight the potential of non-contact UV-Vis spectroscopy for the
      assessment of water contamination. A system built on the concept would be able to
      monitor wastewater pollution continuously, without the need for laborious sample
      collection and subsequent laboratory analysis. Furthermore, since no parts of the
      system are in contact with the wastewater stream the need for maintenance is
      minimised.

PMID- 24901342
TI  - Endothelin-1 promotes survival and chemoresistance in chronic lymphocytic
      leukemia B cells through ETA receptor.
AB  - The endothelin axis, comprising endothelins (ET-1, ET-2 and ET-3) and their
      receptors (ET(A)R and ETBR), has emerged as relevant player in tumor growth and
      metastasis. Here, we investigated the involvement of ET-1/ET(A)R axis in chronic
      lymphocytic leukemia (CLL). CLL cells expressed higher levels of ET-1 and ETA
      receptor as compared to normal B cells. ET-1 peptide stimulated phosphoinositide
      3-kinase and mitogen-activated protein kinase signaling pathways, improved
      survival and promoted proliferation of leukemic cells throughout ET(A)R
      triggering. Moreover, the blockade of ET(A)R by the selective antagonist BQ-123
      inhibited the survival advantage acquired by CLL cells in contact with
      endothelial layers. We also found that blocking ET(A)R via BQ-123 interferes with
      ERK phosphorylation and CLL pro-survival effect mediated by B-cell receptor (BCR)
      activation. The pro-apoptotic effect of phosphoinositide-3-kinase delta inhibitor
      idelalisib and mitogen-activated protein kinase inhibitor PD98059 was decreased
      by the addition of ET-1 peptide. Then, ET-1 also reduced the cytotoxic effect of
      fludarabine on CLL cells cultured alone or co-cultured on endothelial layers.
      ET(A)R blockade by BQ-123 inhibited the ET-1-mediated protection against drug
      induced apoptosis. Lastly, higher plasma levels of big ET-1 were detected in
      patients (n = 151) with unfavourable prognostic factors and shorter time to first
      treatment. In conclusion, our data describe for the first time a role of ET
      1/ET(A)R signaling in CLL pathobiology. ET-1 mediates survival, drug-resistance,
      and growth signals in CLL cells that can be blocked by ET(A)R inhibition.

PMID- 24901343
TI  - Evaluation of ERIC-PCR as genotyping method for Corynebacterium
      pseudotuberculosis isolates.
AB  - The aim of this study was to evaluate the Enterobacterial Repetitive Intergenic
      Consensus (ERIC-PCR) as a tool for molecular typing of C. pseudotuberculosis
      isolates from eight different hosts in twelve countries. Ninety-nine C.
      pseudotuberculosis field strains, one type strain (ATCC 19410T) and one vaccine
      strain (1002) were fingerprinted using the ERIC-1R and ERIC-2 primers, and the
      ERIC-1R+ERIC-2 primer pair. Twenty-nine different genotypes were generated by
      ERIC 1-PCR, 28 by ERIC 2-PCR and 35 by ERIC 1+2-PCR. The discriminatory index
      calculated for ERIC 1, ERIC 2, and ERIC 1+2-PCR was 0.89, 0.86, and 0.92,
      respectively. Epidemiological concordance was established for all ERIC-PCR
      assays. ERIC 1+2-PCR was defined as the best method based on suitability of the
      amplification patterns and discriminatory index. Minimal spanning tree for ERIC
      1+2-PCR revealed three major clonal complexes and clustering around nitrate
      positive (biovar Equi) and nitrate-negative (biovar Ovis) strains. Therefore,
      ERIC 1+2-PCR proved to be the best technique evaluated in this study for
      genotyping C. pseudotuberculosis strains, due to its usefulness for molecular
      epidemiology investigations. 

PMID- 24901344
TI  - Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus
      aureus infection and human sepsis.
AB  - Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to
      identify genetic determinants of susceptibility to S. aureus, and evaluate their
      function with regard to S. aureus infection. One QTL region on chromosome 11
      containing 422 genes was found to be significantly associated with susceptibility
      to S. aureus infection. Of these 422 genes, whole genome transcription profiling
      identified five genes (Dcaf7, Dusp3, Fam134c, Psme3, and Slc4a1) that were
      significantly differentially expressed in a) S. aureus -infected susceptible
      (A/J) vs. resistant (C57BL/6J) mice and b) humans with S. aureus blood stream
      infection vs. healthy subjects. Three of these genes (Dcaf7, Dusp3, and Psme3)
      were down-regulated in susceptible vs. resistant mice at both pre- and post
      infection time points by qPCR. siRNA-mediated knockdown of Dusp3 and Psme3
      induced significant increases of cytokine production in S. aureus-challenged
      RAW264.7 macrophages and bone marrow derived macrophages (BMDMs) through
      enhancing NF-kappaB signaling activity. Similar increases in cytokine production
      and NF-kappaB activity were also seen in BMDMs from CSS11 (C57BL/6J background
      with chromosome 11 from A/J), but not C57BL/6J. These findings suggest that Dusp3
      and Psme3 contribute to S. aureus infection susceptibility in A/J mice and play a
      role in human S. aureus infection. 

PMID- 24901345
TI  - Prevalence of metabolic syndrome is higher among non-obese PCOS women with
      hyperandrogenism and menstrual irregularity in Korea.
AB  - BACKGROUND: Hyperandrogenism (HA) has been linked with several components of
      metabolic syndrome (MetS). Few studies in Asian women have evaluated the
      important risk factors for and prevalence of MetS according to PCOS subtype. In
      this study, we investigated differences in metabolic parameters and the
      prevalence of MetS in two major phenotypic subgroups of PCOS in Korea.
      Furthermore, we investigated the relationship between HA-associated parameters
      and MetS. MATERIALS AND METHODS: This cross-sectional observational study was
      conducted from May 2010 to December 2011 in Korea. A total of 837 females with
      PCOS, aged 15-40, were recruited from Departments of Obstetrics and Gynecology at
      13 hospitals. Of those, 700 subjects with either polycystic ovaries
      (PCO)+HA+oligomenorrhea/amenorrhea (O) or PCO+O were eligible for this study.
      MetS was diagnosed according to the modified National Cholesterol Education
      Program (NCEP) Adult Treatment Panel (ATP) III guidelines and the International
      Diabetes Federation (IDF) criteria. RESULTS: MetS was more prevalent in the
      PCO+HA+O group (19.7%) than in the PCO+O (11.9%) group. There were statistically
      significant trends for an increased risk of MetS in the PCO+HA+O group compared
      to the PCO+O group. After adjustment for age, the odds ratio of MetS was 2.192 in
      non-obese subjects with PCO+HA+O compared to those with PCO+O, whereas the risk
      of MetS was not different in obese patients. Multivariate logistic regression
      analysis showed that high free androgen index and low sex hormone-binding
      globulin were significantly associated with MetS in non-obese women with PCOS,
      with odds ratios of 4.234 (95% CI, 1.893-9.474) and 4.612 (95% CI, 1.978-10.750),
      respectively. However, no associations were detected between MetS and SHBG and
      FAI in obese PCOS subjects. CONCLUSIONS: Our results indicate that HA and its
      associated parameters (FAI and SHBG) are significantly associated with MetS in
      non-obese PCOS subjects, whereas this association was not observed in obese
      subjects.

PMID- 24901346
TI  - The usefulness of whole-exome sequencing in routine clinical practice.
AB  - PURPOSE: Reports of the use of whole-exome sequencing in clinical practice are
      limited. We report our experience with whole-exome sequencing in 115 patients in
      a single center and evaluate its feasibility and clinical usefulness in clinical
      care. METHODS: Whole-exome sequencing was utilized based on the judgment of three
      clinical geneticists. We describe age, gender, ethnicity, consanguinity,
      indication for testing, family history, insurance, laboratory results, clinician
      interpretation of results, and impact on patient care. RESULTS: Most patients
      were children (78.9%). The most common indications for testing were birth defects
      (24.3%) and developmental delay (25.2%). We identified four new candidate human
      disease genes and possibly expanded the disease phenotypes associated with five
      different genes. Establishing a diagnosis led to discontinuation of additional
      planned testing in all patients, screening for additional manifestations in
      eight, altered management in fourteen, novel therapy in two, identification of
      other familial mutation carriers in five, and reproductive planning in six.
      CONCLUSION: Our results show that whole-exome sequencing is feasible, has
      clinical usefulness, and allows timely medical interventions, informed
      reproductive choices, and avoidance of additional testing. Our results also
      suggest phenotype expansion and identification of new candidate disease genes
      that would have been impossible to diagnose by other targeted testing methods.

PMID- 24901347
TI  - Neurofibromatosis type 1 and chronic neurological conditions in the United
      States: an administrative claims analysis.
AB  - PURPOSE: Neurofibromatosis type 1 has been linked to several neurological
      conditions, including epilepsy, Parkinson disease, headache, multiple sclerosis,
      and sleep disturbances, predominantly through case reports and patient series
      that lack comparison groups. Our objective was to assess whether specific
      neurological conditions occur more frequently in individuals with
      neurofibromatosis type 1 versus those without neurofibromatosis type 1. METHODS:
      We used the 2006-2010 MarketScan Commercial Claims and Encounters database to
      examine associations between neurological conditions and neurofibromatosis type
      1. The neurofibromatosis type 1 group was identified through >=2 International
      Classification of Diseases, Ninth Revision, Clinical Modification
      neurofibromatosis codes (237.70, 237.71) occurring >=30 days apart or one
      inpatient neurofibromatosis code. A nonneurofibromatosis type 1 comparison group
      was frequency matched to the neurofibromatosis type 1 group on age and enrollment
      length at a 10:1 ratio. Unconditional logistic regression was employed to
      calculate adjusted odds ratios and 95% confidence intervals for associations
      between neurofibromatosis and neurological conditions. RESULTS: Compared with the
      nonneurofibromatosis type 1 group (n = 85,790), the neurofibromatosis type 1
      group (n = 8,579) had significantly higher odds of health insurance claims for
      epilepsy (odds ratio: 7.3; 95% confidence interval: 6.4-8.3), Parkinson disease
      (odds ratio: 3.1; 95% confidence interval: 1.3-7.5), headache (odds ratio: 2.9;
      95% confidence interval: 2.6-3.1), multiple sclerosis (odds ratio: 1.9; 95%
      confidence interval: 1.2-2.9), and sleep disturbances/disorder (odds ratio: 1.4;
      95% confidence interval: 1.2-3.6). CONCLUSION: This large study provides strong
      evidence for positive associations between several neurological conditions and
      neurofibromatosis type 1.

PMID- 24901349
TI  - Survival, recruitment, and population growth rate of an important mesopredator:
      the northern raccoon.
AB  - Populations of mesopredators (mid-sized mammalian carnivores) are expanding in
      size and range amid declining apex predator populations and ever-growing human
      presence, leading to significant ecological impacts. Despite their obvious
      importance, population dynamics have scarcely been studied for most mesopredator
      species. Information on basic population parameters and processes under a range
      of conditions is necessary for managing these species. Here we investigate
      survival, recruitment, and population growth rate of a widely distributed and
      abundant mesopredator, the northern raccoon (Procyon lotor), using Pradel's
      temporal symmetry models and >6 years of monthly capture-mark-recapture data
      collected in a protected area. Monthly apparent survival probability was higher
      for females (0.949, 95% CI = 0.936-0.960) than for males (0.908, 95% CI = 0.893
      0.920), while monthly recruitment rate was higher for males (0.091, 95% CI =
      0.078-0.106) than for females (0.054, 95% CI = 0.042-0.067). Finally, monthly
      realized population growth rate was 1.000 (95% CI = 0.996-1.004), indicating that
      our study population has reached a stable equilibrium in this relatively
      undisturbed habitat. There was little evidence for substantial temporal variation
      in population growth rate or its components. Our study is one of the first to
      quantify survival, recruitment, and realized population growth rate of raccoons
      using long-term data and rigorous statistical models.

PMID- 24901348
TI  - Accurate mitochondrial DNA sequencing using off-target reads provides a single
      test to identify pathogenic point mutations.
AB  - PURPOSE: Mitochondrial disorders are a common cause of inherited metabolic
      disease and can be due to mutations affecting mitochondrial DNA or nuclear DNA.
      The current diagnostic approach involves the targeted resequencing of
      mitochondrial DNA and candidate nuclear genes, usually proceeds step by step, and
      is time consuming and costly. Recent evidence suggests that variations in
      mitochondrial DNA sequence can be obtained from whole-exome sequence data,
      raising the possibility of a comprehensive single diagnostic test to detect
      pathogenic point mutations. METHODS: We compared the mitochondrial DNA sequence
      derived from off-target exome reads with conventional mitochondrial DNA Sanger
      sequencing in 46 subjects. RESULTS: Mitochondrial DNA sequences can be reliably
      obtained using three different whole-exome sequence capture kits. Coverage
      correlates with the relative amount of mitochondrial DNA in the original genomic
      DNA sample, heteroplasmy levels can be determined using variant and total read
      depths, and-providing there is a minimum read depth of 20-fold-rare sequencing
      errors occur at a rate similar to that observed with conventional Sanger
      sequencing. CONCLUSION: This offers the prospect of using whole-exome sequence in
      a diagnostic setting to screen not only all protein coding nuclear genes but also
      all mitochondrial DNA genes for pathogenic mutations. Off-target mitochondrial
      DNA reads can also be used to assess quality control and maternal ancestry,
      inform on ethnic origin, and allow genetic disease association studies not
      previously anticipated with existing whole-exome data sets.

PMID- 24901351
TI  - What factors determine therapists' acceptance of new technologies for
      rehabilitation - a study using the Unified Theory of Acceptance and Use of
      Technology (UTAUT).
AB  - PURPOSE: The aim of this study was to examine what factors affect the acceptance
      behavior and use of new technologies for rehabilitation by therapists at a large
      rehabilitation hospital in Canada. METHOD: A self-administrated paper-based
      survey was created by adapting scales with high levels of internal consistency in
      prior research using the Unified Theory of Acceptance and Use of Technology
      (UTAUT). Items were scored on a 7-point Likert scale, ranging from "strongly
      disagree (1)" to "strongly agree (7)". The target population was all occupational
      therapists (OT) and physical therapists (PT) involved with the provision of
      therapeutic interventions at the hospital. Our research model was tested using
      partial least squares (PLS) technique. RESULTS: Performance expectancy was the
      strongest salient construct for behavioral intention to use new technologies in
      rehabilitation, whereas neither effort expectancy nor social influence were
      salient constructs for behavioral intention to use new technologies; (4)
      facilitating condition and behavioral intention to use new technologies were
      salient constructs for current use of new technologies in rehabilitation, with
      facilitating condition the strongest salient for current use of new technologies
      in rehabilitation. CONCLUSION: In a large rehabilitation hospital where use of
      new technologies in rehabilitation is not mandatory, performance expectancy, or
      how the technology can help in therapists' work, was the most important factor in
      determining therapists' acceptance and use of technologies. However, effort
      expectancy and social influence constructs were not important, i.e. therapists
      were not influenced by the degree of difficulty or social pressures to use
      technologies. Behavioral intention and facilitating condition, or institutional
      support, are related to current use of new technologies in rehabilitation.

PMID- 24901350
TI  - Health websites: accessibility and usability for American sign language users.
AB  - To date, there have been efforts toward creating better health information access
      for Deaf American Sign Language (ASL) users. However, the usability of websites
      with access to health information in ASL has not been evaluated. Our article
      focuses on the usability of four health websites that include ASL videos. We seek
      to obtain ASL users' perspectives on the navigation of these ASL-accessible
      websites, finding the health information that they needed, and perceived ease of
      understanding ASL video content. ASL users (n = 32) were instructed to find
      specific information on four ASL-accessible websites, and answered questions
      related to (a) navigation to find the task, (b) website usability, and (c) ease
      of understanding ASL video content for each of the four websites. Participants
      also gave feedback on what they would like to see in an ASL health library
      website, including the benefit of added captioning and/or signer model to medical
      illustration of health videos. Participants who had lower health literacy had
      greater difficulty in finding information on ASL-accessible health websites. This
      article also describes the participants' preferences for an ideal ASL-accessible
      health website, and concludes with a discussion on the role of accessible
      websites in promoting health literacy in ASL users. 

PMID- 24901352
TI  - Diversity of transition pathways in the course of crystallization into ice VII.
AB  - We report various types of pathways emerging in the course of freezing into a
      high pressure ice VII by large-scale molecular dynamics (MD) simulations at 10
      GPa, 425 K. Some trajectories showed an apparently stepwise transition via the
      unique metastable "phase" in accordance with Ostwald's step rule. The metastable
      structure was identified as one of the tetrahedrally close-packed structures
      having the nature of a rotator phase (plastic phase). The unit cell consists of
      21 water molecules that has not yet been reported by simulation or by
      experiments. Structure analysis of numerous trajectories reveals that the
      nucleation of ice VII easily occurs at the grain boundaries of the metastable
      embryos, known as epitaxy-mediated transformation in line with Ostwald's step
      rule. The size of the grain boundaries is thus responsible for the lifetime of
      the metastable phase. On the other hand, once the embryo of ice VII appears prior
      to that of the metastable phase in liquid, direct transition to ice VII takes
      place. We also show that the plastic behavior of the metastable phase is not
      uniform but is sensitive to the interaction strength of adjacent molecules and
      the local structure, thus we call "partially plastic ice". 

PMID- 24901354
TI  - The bright-nights and dim-days of the urban photoperiod: implications for
      circadian rhythmicity, metabolism and obesity.
AB  - Artificial light decreases the amplitude of daily rhythms in human lifestyle
      principally by permitting activity and food intake to occur during hours of
      darkness, and allowing day-time activity to occur in dim light, indoors.
      Endogenous circadian timing mechanisms that oscillate with a period of 24 h have
      evolved to ensure physiology is synchronized with the daily variations in light,
      food, and social cues of the environment. Artificial light affects the
      synchronization between these oscillators, and metabolic disruption may be one
      consequence of this. By dampening the amplitude of environmental timing cues and
      disrupting circadian rhythmicity, artificial lighting might initiate metabolic
      disruption and contribute to the association between global urbanization and
      obesity. The aim of this review is to explore the historical, physiological, and
      epidemiological relationships between artificial light and circadian and
      metabolic dysfunction.

PMID- 24901353
TI  - Fluorescent silver nanoclusters stabilized by DNA scaffolds.
AB  - Fluorescent silver nanoclusters, in particular DNA stabilized (templated) silver
      nanoclusters, have attracted much attention because of their molecule-like
      optical properties, strong fluorescence and good biocompatibility. In this
      feature article, we summarize the DNA stabilized silver nanoclusters from the
      viewpoints of synthesis, optical properties, as well as recent applications in
      biological detection and imaging. 

PMID- 24901355
TI  - Activation and recruitment of brown adipose tissue as anti-obesity regimens in
      humans.
AB  - Brown adipose tissue (BAT) is the site of sympathetically activated adaptive
      thermogenesis during cold exposure and after hyperphagia, thereby controlling
      whole-body energy expenditure (EE) and body fat. BAT thermogenesis is primarily
      dependent on the energy-dissipating activity of uncoupling protein 1 (UCP1).
      There are two types of UCP1-expressing adipocyte, classical brown and beige/brite
      adipocytes. Recent radionuclide studies have demonstrated the existence of
      metabolically active BAT composed of mainly beige/brite adipocytes in adult
      humans. Human BAT is activated by acute cold exposure, being positively
      correlated to cold-induced increases in EE. The inverse relationship between the
      BAT activity and body fatness suggests that BAT, because of its energy
      dissipating activity, is protective against body fat accumulation. In fact,
      either repeated cold exposure or daily ingestion of some food ingredients acting
      on transient receptor potential channels recruited BAT in association with
      increased EE and decreased body fat. Moreover, possible contribution of BAT to
      glucose tolerance has been suggested. In addition to the sympathetic nervous
      system, some endocrine factors also have potential for activation/recruitment of
      BAT. Thus, BAT is a promising therapeutic target for combating human obesity and
      related metabolic disorders. 

PMID- 24901357
TI  - Comparison of self-report and performance-based measures of everyday functioning
      in individuals with schizophrenia: implications for measure selection.
AB  - INTRODUCTION: Both self-report and performance-based measures are often used in
      assessment of everyday functioning for individuals with schizophrenia. However,
      there is little evidence of overlap between them, and there are no established
      standards for which measures might be most appropriate. In order to better
      understand differences among these types of measures, we examined relationships
      between a self-report and two performance-based measures of everyday functioning.
      We also examined their patterns of interrelationships to neurocognition and
      psychiatric symptoms. METHODS: Participants were 71 outpatients with
      schizophrenia spectrum disorder. Measures of everyday functioning (Independent
      Living Skill Survey-Self Report (ILSS-SR); University of California San Diego
      Performance-based Skills Assessment; and Medication Management Ability
      Assessment), cognition and psychiatric symptoms were administered. Correlation
      analyses were conducted to examine the relationships among the functioning
      measures, and their relationships to cognition and symptoms. Regression analyses
      further examined the unique contributions of neurocognitive and symptom variables
      to functional measures. RESULTS: Consistent with the literature, the two
      performance-based measures were related to each other, but not to the self-report
      measure. Whereas the performance-based measures were related to neurocognition
      but not to the psychiatric symptoms, the opposite pattern was observed for the
      self-report measure. CONCLUSIONS: The pattern of interrelationships among these
      self-report and performance-based measures suggests that they tap different
      aspects of everyday functioning. This has important implications for measure
      selection, particularly for evaluating intervention outcomes. When targeting
      symptoms, a self-report measure like the ILSS-SR may be more appropriate, whereas
      a performance-based measure may be more sensitive to functional changes
      subsequent to treatments targeting cognition.

PMID- 24901358
TI  - Chronic pain and mortality: a systematic review.
AB  - BACKGROUND: Chronic pain is common, often widespread and has a substantial impact
      on health and quality of life. The relationship between chronic pain and
      mortality is unclear. This systematic review aimed to identify and evaluate
      evidence for a relationship between chronic pain and mortality. METHODS: A search
      of ten electronic databases including EMBASE and MEDLINE was conducted in March
      2012, and updated until March 2014. Observational studies investigating the
      association between chronic or widespread pain (including fibromyalgia) and
      mortality were included. Risk of bias was assessed and a meta-analysis was
      undertaken to quantify heterogeneity and pool results. A narrative review was
      undertaken to explore similarities and differences between the included studies.
      RESULTS: Ten studies were included in the review. Three reported significant
      associations between chronic or widespread pain and mortality in unadjusted
      results. In adjusted analyses, four studies reported a significant association.
      The remaining studies reported no statistically significant association. A meta
      analysis showed statistically significant heterogeneity of results from studies
      using comparable outcome measures (n = 7)(I2 = 78.8%) and a modest but non
      significant pooled estimate (MRR1.14,95%CI 0.95-1.37) for the relationship
      between chronic pain and all-cause mortality. This association was stronger when
      analysis was restricted to studies of widespread pain (n = 5,I2 = 82.3%)
      MRR1.22(95%CI 0.93-1.60). The same pattern was observed with deaths from cancer
      and cardiovascular diseases. Heterogeneity is likely to be due to differences in
      study populations, follow-up time, pain phenotype, methods of analysis and use of
      confounding factors. CONCLUSION: This review showed a mildly increased risk of
      death in people with chronic pain, particularly from cancer. However, the small
      number of studies and methodological differences prevented clear conclusions from
      being drawn. Consistently applied definitions of chronic pain and further
      investigation of the role of health, lifestyle, social and psychological factors
      in future studies will improve understanding of the relationship between chronic
      pain and mortality.

PMID- 24901359
TI  - Laparoscopic versus open radical cystectomy for elderly patients over 75-year
      old: a single center comparative analysis.
AB  - PURPOSE: To explore the morbidity, mortality and oncological results of
      laparoscopic radical cystectomy (LRC) in the elderly patients over 75-year-old in
      contrast with open radical cystectomy (ORC). MATERIALS AND METHODS: We analyzed
      46 radical cystectomies from January 2009 to December 2013 in patients over 75
      year-old in our institute, 21 patients in the LRC group and 25 in the ORC group.
      Demographic parameters, operative variables and perioperative outcome were
      retrospectively collected and analyzed between the two groups. Perioperative
      morbidity and mortality were categorized as early (within 90 days after surgery)
      or late (more than 90 days) according to the time of occurrence. RESULTS:
      Patients in both groups had comparable preoperative characteristics. A
      significant longer operative time (418 vs. 337 min, p = 0.018) and less estimated
      blood loss (400 vs. 500 ml p = 0.038) were observed in LRC group compared with
      ORC group. Infection and ileus were the most common early complications after
      surgery. Patients underwent ORC suffered from significantly more postoperative
      ileus (28.0% vs. 4.8%, P = 0.038) and infection (40% vs. 9.5%, P = 0.019) than
      LRC group within 90 days after surgery. The mortality rate was 4.7% (1/21) and 4%
      (1/25) for LRC group and ORC group respectively. At a median follow-up of 21
      months (range 2-61 months), the Kaplan-Meier survival curves and log-rank
      analysis demonstrate that there were no significant differences between the LRC
      and ORC groups in the 3-year overall, cancer-specific, or recurrence-free
      survival rates. CONCLUSIONS: It is suggested that LRC should be recommended as
      the primary intervention to treat muscle invasive or high risk non-muscle
      invasive bladder cancer in elderly patients with a relative long life expectancy.

PMID- 24901360
TI  - A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and
      oxaliplatin in patients with resectable pancreas adenocarcinoma.
AB  - BACKGROUND: The role for neoadjuvant systemic therapy in resectable pancreas
      adenocarcinoma remains undefined. OBJECTIVE: We evaluated the efficacy of
      gemcitabine and oxaliplatin administered as preoperative therapy in patients with
      resectable pancreas adenocarcinoma. METHODS: Eligible patients were screened
      using computed tomography-pancreas angiography, laparoscopy, endoscopic
      ultrasonography, and fine-needle aspiration cytology to identify 38 patients who
      received 4 cycles of neoadjuvant gemcitabine 1000 mg/m intravenously over 100
      minutes and oxaliplatin 80 mg/m intravenously over 2 hours, every 2 weeks.
      Patients whose tumors remained resectable at restaging proceeded to operation and
      subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m intravenously
      over 30 minutes days 1, 8, and 15 every 4 weeks). The primary endpoint was 18
      month overall survival and secondary endpoints included radiological, tumor
      marker and pathological response to neoadjuvant therapy, time to recurrence,
      patterns of failure, and feasibility of obtaining preoperative core biopsies.
      RESULTS: Thirty-five of 38 patients (92%) completed neoadjuvant therapy. Twenty
      seven patients underwent tumor resection (resectability rate 71%), of which 26
      initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all
      planned therapy. The 18-month survival was 63% (24 patients alive). The median
      overall survival for all 38 patients was 27.2 months (95% confidence interval: 17
      NA) and the median disease-specific survival was 30.6 months (95% confidence
      interval: 19-NA). CONCLUSIONS: This study met its endpoint and provided a signal
      suggesting that exploration of neoadjuvant systemic therapy is worthy of further
      investigation in resectable pancreas adenocarcinoma. Improved patient selection
      and more active systemic regimens are key. Clinical trials identification:
      NCT00536874.

PMID- 24901361
TI  - A clinical algorithm for fine-needle aspiration molecular testing effectively
      guides the appropriate extent of initial thyroidectomy.
AB  - OBJECTIVE: To test whether a clinical algorithm using routine cytological
      molecular testing (MT) promotes initial total thyroidectomy (TT) for clinically
      significant thyroid cancer (sTC) and/or correctly limits surgery to lobectomy
      when appropriate. BACKGROUND: Either TT or lobectomy is often needed to diagnose
      differentiated thyroid cancer. Determining the correct extent of initial
      thyroidectomy is challenging. METHODS: After implementing an algorithm for
      prospective MT of in-house fine-needle aspiration biopsy specimens, we conducted
      a single-institution cohort study of all patients (N = 671) with nonmalignant
      cytology who had thyroidectomy between October 2010 and March 2012, cytological
      diagnosis using 2008 Bethesda criteria, and 1 or more indications for
      thyroidectomy by 2009 American Thyroid Association guidelines. sTC was defined by
      histological differentiated thyroid cancer of 1 cm or more and/or lymph node
      metastasis. Cohort 2 patients did not have MT or had unevaluable results. In
      cohort 1, MT for a multigene mutation panel was performed for nonbenign cytology,
      and positive MT results indicated initial TT. RESULTS: MT guidance was associated
      with a higher incidence of sTC after TT (P = 0.006) and a lower rate of sTC after
      lobectomy (P = 0.03). Without MT results, patients with indeterminate (follicular
      lesion of undetermined significance/follicular or oncocytic neoplasm) cytology
      who received initial lobectomy were 2.5 times more likely to require 2-stage
      surgery for histological sTC (P < 0.001). In the 501 patients with non-sTC for
      whom lobectomy was the appropriate extent of surgery, lobectomy was correctly
      performed more often with routine preoperative MT (P = 0.001). CONCLUSIONS: Fine
      needle aspiration biopsy MT for BRAF, RAS, PAX8-PPARgamma, and RET-PTC expedites
      optimal initial surgery for differentiated thyroid cancer, facilitating succinct
      definitive management for patients with thyroid nodules.

PMID- 24901356
TI  - Circadian gene variants in cancer.
AB  - Humans as diurnal beings are active during the day and rest at night. This daily
      oscillation of behavior and physiology is driven by an endogenous circadian clock
      not environmental cues. In modern societies, changes in lifestyle have led to a
      frequent disruption of the endogenous circadian homeostasis leading to increased
      risk of various diseases including cancer. The clock is operated by the feedback
      loops of circadian genes and controls daily physiology by coupling cell
      proliferation and metabolism, DNA damage repair, and apoptosis in peripheral
      tissues with physical activity, energy homeostasis, immune and neuroendocrine
      functions at the organismal level. Recent studies have revealed that defects in
      circadian genes due to targeted gene ablation in animal models or single
      nucleotide polymorphism, deletion, deregulation and/or epigenetic silencing in
      humans are closely associated with increased risk of cancer. In addition,
      disruption of circadian rhythm can disrupt the molecular clock in peripheral
      tissues in the absence of circadian gene mutations. Circadian disruption has
      recently been recognized as an independent cancer risk factor. Further study of
      the mechanism of clock-controlled tumor suppression will have a significant
      impact on human health by improving the efficiencies of cancer prevention and
      treatment.

PMID- 24901363
TI  - Histone modifications are associated with transcript isoform diversity in normal
      and cancer cells.
AB  - Mechanisms that generate transcript diversity are of fundamental importance in
      eukaryotes. Although a large fraction of human protein-coding genes and lincRNAs
      produce more than one mRNA isoform each, the regulation of this phenomenon is
      still incompletely understood. Much progress has been made in deciphering the
      role of sequence-specific features as well as DNA-and RNA-binding proteins in
      alternative splicing. Recently, however, several experimental studies of
      individual genes have revealed a direct involvement of epigenetic factors in
      alternative splicing and transcription initiation. While histone modifications
      are generally correlated with overall gene expression levels, it remains unclear
      how histone modification enrichment affects relative isoform abundance.
      Therefore, we sought to investigate the associations between histone
      modifications and transcript diversity levels measured by the rates of
      transcription start-site switching and alternative splicing on a genome-wide
      scale across protein-coding genes and lincRNAs. We found that the relationship
      between enrichment levels of epigenetic marks and transcription start-site
      switching is similar for protein-coding genes and lincRNAs. Furthermore, we found
      associations between splicing rates and enrichment levels of H2az, H3K4me1,
      H3K4me2, H3K4me3, H3K9ac, H3K9me3, H3K27ac, H3K27me3, H3K36me3, H3K79me2, and
      H4K20me, marks traditionally associated with enhancers, transcription initiation,
      transcriptional repression, and others. These patterns were observed in both
      normal and cancer cell lines. Additionally, we developed a novel computational
      method that identified 840 epigenetically regulated candidate genes and predicted
      transcription start-site switching and alternative exon splicing with up to 92%
      accuracy based on epigenetic patterning alone. Our results suggest that the
      epigenetic regulation of transcript isoform diversity may be a relatively common
      genome-wide phenomenon representing an avenue of deregulation in tumor
      development. 

PMID- 24901364
TI  - Dementia care in the context of primary care reform: an integrative review.
AB  - OBJECTIVES: The purpose of this review was to determine the influence of the
      growing body of evidence about the attributes of high-performing primary care
      systems on the literature related to the primary care of people living with
      dementia. METHODS: In this integrative review, we examined a broad range of
      published and grey literature (2000-2013) about the primary care of dementia,
      using a systematic approach set up in advance of the literature search. The
      review was guided by two questions: What are the evident models of primary care
      for dementia? How do the models line up with the other attributes of high
      performing primary care? RESULTS: Three models were noted: carved-out, co
      managed, and integrative-hub, all informed by different assumptions about the
      role of primary care in dementia. The models varied in alignment with the
      attributes of high-performing primary care, although we found very little
      attention to accessibility, relational continuity or comprehensiveness of care.
      CONCLUSIONS: We know what we need to pay attention to in building our primary
      care system - and no population will put the performance of primary care more to
      the test over the next two decades than the rapidly growing number of people who
      will be living with complex chronic conditions like dementia. Recent literature
      around primary care and dementia shows promise in attending to some of the
      attributes of high-performing primary care, yet much more work is needed if we
      are to truly leverage the potential value of primary care in addressing the needs
      of these complex and numerous future patients.

PMID- 24901365
TI  - A safety and pharmacokinetic trial assessing delivery of dapivirine from a
      vaginal ring in healthy women.
AB  - OBJECTIVES: Women-initiated HIV-prevention products are urgently needed. To
      address this need, a trial was conducted to assess the safety and
      pharmacokinetics of a silicone elastomer matrix vaginal ring containing 25 mg of
      the antiretroviral drug dapivirine when used continuously for 28 consecutive
      days. METHODS: A double-blind, randomized, placebo-controlled trial was conducted
      in 16 healthy, HIV-negative women, 18-40 years of age, who were randomized 1:1 to
      use either the active or matching placebo ring for 28 days. Participants were
      followed during and for 28 days after ring use for safety and pharmacokinetic
      evaluations. RESULTS: The dapivirine vaginal ring was safe and well tolerated
      with no differences in safety endpoints between the active and placebo ring. The
      concentration-time plots of dapivirine in vaginal fluid were indicative of a
      sustained release of dapivirine over the 28 days of use. Dapivirine vaginal fluid
      concentrations were highest near the ring, followed by the cervix and introitus
      (mean Cmax of 80, 67 and 31 MUg/g, respectively). Vaginal fluid concentrations of
      dapivirine on the day of ring removal (day 28) at all three collection sites
      exceeded by more than 3900-fold the IC99 for dapivirine in a tissue explant
      infection model. Plasma dapivirine concentrations were low (< 1 ng/ml) and
      remained well below those observed at the maximum tolerated dose for oral
      treatment (mean Cmax of 2286  ng/ml). CONCLUSION: The dapivirine vaginal ring has
      a safety and pharmacokinetic profile that supports its use as a sustained-release
      topical microbicide for HIV-1 prevention in women.

PMID- 24901366
TI  - Do editorial policies support ethical research? A thematic text analysis of
      author instructions in psychiatry journals.
AB  - INTRODUCTION: According to the Declaration of Helsinki and other guidelines,
      clinical studies should be approved by a research ethics committee and seek valid
      informed consent from the participants. Editors of medical journals are
      encouraged by the ICMJE and COPE to include requirements for these principles in
      the journal's instructions for authors. This study assessed the editorial
      policies of psychiatry journals regarding ethics review and informed consent.
      METHODS AND FINDINGS: The information given on ethics review and informed consent
      and the mentioning of the ICMJE and COPE recommendations were assessed within
      author's instructions and online submission procedures of all 123 eligible
      psychiatry journals. While 54% and 58% of editorial policies required ethics
      review and informed consent, only 14% and 19% demanded the reporting of these
      issues in the manuscript. The TOP-10 psychiatry journals (ranked by impact
      factor) performed similarly in this regard. CONCLUSIONS: Only every second
      psychiatry journal adheres to the ICMJE's recommendation to inform authors about
      requirements for informed consent and ethics review. Furthermore, we argue that
      even the ICMJE's recommendations in this regard are insufficient, at least for
      ethically challenging clinical trials. At the same time, ideal scientific design
      sometimes even needs to be compromised for ethical reasons. We suggest that
      features of clinical studies that make them morally controversial, but not
      necessarily unethical, are analogous to methodological limitations and should
      thus be reported explicitly. Editorial policies as well as reporting guidelines
      such as CONSORT should be extended to support a meaningful reporting of ethical
      research.

PMID- 24901368
TI  - Changes in expression pattern of selected endometrial proteins following
      mesenchymal stem cells infusion in mares with endometrosis.
AB  - Mesenchymal stem cells (MSCs) due to their self-renewal potential and
      differentiation capacity are useful for tissue regeneration. Immunomodulatory and
      trophic properties of MSCs were demonstrated suggesting their use as medicinal
      signaling cells able to positively change local environment in injured tissue.
      Equine endometrosis is a progressive degenerative disease responsible for
      glandular alterations and endometrial fibrosis which causes infertility in mares.
      More precisely, this disease is characterized by phenotypic changes in the
      expression pattern of selected endometrial proteins. Currently, no effective
      treatment is available for endometrosis. Herein, we aimed at the evaluation of
      expression pattern of these proteins after allogeneic equine adipose tissue
      derived multipotent mesenchymal stem cells (eAT-MSCs) infusion as well as at
      testing the capacity of these cells to promote endometrial tissue remodeling in
      mares with endometrosis. eAT-MSC (2 * 10(7)/animal) were transplanted into mares'
      uterus and control animals received only placebo. Uterine biopsies were collected
      before (day 0) and after (days 7, 21 and 60) cells transplantation. Conventional
      histopathology as well as expression analysis of such proteins as laminin,
      vimentin, Ki-67-antigen, alpha-smooth muscle actin (alpha-SMA) and cytokeratin 18
      (CK18) have been performed before and after eAT-MSCs transplantation. We
      demonstrated that eAT-MSCs induced early (at day 7) remodeling of endometrial
      tissue microenvironment through changes observed in intra cellular and intra
      glandular localization of aforementioned proteins. We demonstrated that eAT-MSCs
      were able to positively modulate the expression pattern of studied secretory
      proteins as well as, to promote the induction of glandular epithelial cells
      proliferation suggesting local benefits to committed endometrial tissue
      environment after eAT-MSCs transplantation.

PMID- 24901367
TI  - Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from
      pathogenic mutations in TRIT1 and its substrate tRNA.
AB  - Identifying the genetic basis for mitochondrial diseases is technically
      challenging given the size of the mitochondrial proteome and the heterogeneity of
      disease presentations. Using next-generation exome sequencing, we identified in a
      patient with severe combined mitochondrial respiratory chain defects and
      corresponding perturbation in mitochondrial protein synthesis, a homozygous
      p.Arg323Gln mutation in TRIT1. This gene encodes human tRNA
      isopentenyltransferase, which is responsible for i6A37 modification of the
      anticodon loops of a small subset of cytosolic and mitochondrial tRNAs.
      Deficiency of i6A37 was previously shown in yeast to decrease translational
      efficiency and fidelity in a codon-specific manner. Modelling of the p.Arg323Gln
      mutation on the co-crystal structure of the homologous yeast
      isopentenyltransferase bound to a substrate tRNA, indicates that it is one of a
      series of adjacent basic side chains that interact with the tRNA backbone of the
      anticodon stem, somewhat removed from the catalytic center. We show that patient
      cells bearing the p.Arg323Gln TRIT1 mutation are severely deficient in i6A37 in
      both cytosolic and mitochondrial tRNAs. Complete complementation of the i6A37
      deficiency of both cytosolic and mitochondrial tRNAs was achieved by transduction
      of patient fibroblasts with wild-type TRIT1. Moreover, we show that a previously
      reported pathogenic m.7480A>G mt-tRNASer(UCN) mutation in the anticodon loop
      sequence A36A37A38 recognised by TRIT1 causes a loss of i6A37 modification. These
      data demonstrate that deficiencies of i6A37 tRNA modification should be
      considered a potential mechanism of human disease caused by both nuclear gene and
      mitochondrial DNA mutations while providing insight into the structure and
      function of TRIT1 in the modification of cytosolic and mitochondrial tRNAs. 

PMID- 24901370
TI  - Metal-free, efficient oxyfluorination of olefins for the synthesis of alpha
      fluoroketones.
AB  - A novel oxyfluorination of olefin reactions has been developed. The reactions
      involve a metal-free and green catalytic system for the synthesis of alpha
      fluoroketones which is an important building block for organic synthesis.
      Moreover, this reaction system exhibits great functional group tolerance. 

PMID- 24901369
TI  - Ocular and extraocular expression of opsins in the rhopalium of Tripedalia
      cystophora (Cnidaria: Cubozoa).
AB  - A growing body of work on the neuroethology of cubozoans is based largely on the
      capabilities of the photoreceptive tissues, and it is important to determine the
      molecular basis of their light sensitivity. The cubozoans rely on 24 special
      purpose eyes to extract specific information from a complex visual scene to guide
      their behavior in the habitat. The lens eyes are the most studied photoreceptive
      structures, and the phototransduction in the photoreceptor cells is based on
      light sensitive opsin molecules. Opsins are photosensitive transmembrane proteins
      associated with photoreceptors in eyes, and the amino acid sequence of the opsins
      determines the spectral properties of the photoreceptors. Here we show that two
      distinct opsins (Tripedalia cystophora-lens eye expressed opsin and Tripedalia
      cystophora-neuropil expressed opsin, or Tc-leo and Tc-neo) are expressed in the
      Tripedalia cystophora rhopalium. Quantitative PCR determined the level of
      expression of the two opsins, and we found Tc-leo to have a higher amount of
      expression than Tc-neo. In situ hybridization located Tc-leo expression in the
      retinal photoreceptors of the lens eyes where the opsin is involved in image
      formation. Tc-neo is expressed in a confined part of the neuropil and is probably
      involved in extraocular light sensation, presumably in relation to diurnal
      activity. 

PMID- 24901371
TI  - Molecular beam study of the scattering behavior of water molecules from a
      graphite surface.
AB  - Gas flow in nanospaces is greatly affected by the scattering behavior of gas
      molecules on solid surfaces, resulting in unique mass transport properties. In
      this paper, the molecular beam scattering experiment of water molecules on a
      graphite surface was conducted to understand their scattering dynamics in an
      incident energy range that corresponds to their thermal velocity distribution at
      room temperature (35-130 meV). Because of the large adsorption energy (~100 meV),
      the scattering behavior is quite sensitive to the incident energy even within
      this narrow energy range. For relatively large incident energies, the direct
      inelastic and trapping-desorption channels have comparable contributions to the
      scattering process on the surface at 300 K. In contrast, when the incident energy
      decreases well below the adsorption energy on the surface, the trapping
      desorption channel becomes dominant, changing the scattering pattern from
      directional to diffusive scattering. As a result, the tangential momentum
      accommodation coefficient (TMAC), which significantly impacts the mass transport
      in nanospaces, largely depends on the incident energy. A decrease in the incident
      energy from 130 to 35 meV doubles the TMAC (0.42 to 0.86). In addition to the
      incident energy, the TMAC shows a strong dependence on the surface temperature.
      With increasing the surface temperature from 300 to 500 K, the scattering becomes
      more directional because of the increasing contribution of the direct-inelastic
      channel, which reduces the TMAC for the incident beam energy of 35 meV to 0.48. 

PMID- 24901372
TI  - Introduction of pi-complexation into porous aromatic framework for highly
      selective adsorption of ethylene over ethane.
AB  - In this work, we demonstrate for the first time the introduction of pi
      complexation into a porous aromatic framework (PAF), affording significant
      increase in ethylene uptake capacity, as illustrated in the context of Ag(I) ion
      functionalized PAF-1, PAF-1-SO3Ag. IAST calculations using single-component
      isotherm data and an equimolar ethylene/ethane ratio at 296 K reveal that PAF-1
      SO3Ag shows exceptionally high ethylene/ethane adsorption selectivity (Sads: 27
      to 125), far surpassing benchmark zeolite and any other MOF reported in
      literature. The formation of pi-complexation between ethylene molecules and Ag(I)
      ions in PAF-1-SO3Ag has been evidenced by the high isosteric heats of adsorption
      of C2H4 and also proved by in situ IR spectroscopy studies. Transient
      breakthrough experiments, supported by simulations, indicate the feasibility of
      PAF-1-SO3Ag for producing 99.95%+ pure C2H4 in a Pressure Swing Adsorption
      operation. Our work herein thus suggests a new perspective to functionalizing
      PAFs and other types of advanced porous materials for highly selective adsorption
      of ethylene over ethane. 

PMID- 24901373
TI  - Crystallization-induced properties from morphology-controlled organic crystals.
AB  - During the past two decades, many materials chemists have focused on the
      development of organic molecules that can serve as the basis of cost-effective
      and flexible electronic, optical, and energy conversion devices. Among the
      potential candidate molecules, metal-free or metal-containing conjugated organic
      molecules offer high-order electronic conjugation levels that can directly
      support fast charge carrier transport, rapid optoelectric responses, and reliable
      exciton manipulation. Early studies of these molecules focused on the design and
      synthesis of organic unit molecules that exhibit active electrical and optical
      properties when produced in the form of thin film devices. Since then,
      researchers have worked to enhance the properties upon crystallization of the
      unit molecules as single crystals provide higher carrier mobilities and exciton
      recombination yields. Most recently, researchers have conducted in-depth studies
      to understand how crystallization induces property changes, especially those that
      depend on specific crystal surfaces. The different properties that depend on the
      crystal facets have been of particular interest. Most unit molecules have
      anisotropic structures, and therefore produce crystals with several unique
      crystal facets with dissimilar molecular arrangements. These structural
      differences would also lead to diverse electrical conductance, optical
      absorption/emission, and even chemical interaction properties depending on the
      crystal facet investigated. To study the effects of crystallization and crystal
      facet-dependent property changes, researchers must grow or synthesize crystals of
      highly conjugated molecules that have both a variety of morphologies and high
      crystallinity. Morphologically well-defined organic crystals, that form
      structures such as wires, rods, disks, and cubes, provide objects that
      researchers can use to evaluate these material properties. Such structures
      typically occur as single crystals with well-developed facets with dissimilar
      molecular arrangements. Recently, researchers have proposed several approaches
      for the vapor and solution phase synthesis of high quality organic crystals with
      various morphologies. In this Account, we focus on methodologies for the
      synthesis of various organic- and metal-containing highly conjugated molecular
      crystals. We also examine the new optical and chemical properties of these
      materials. In addition, we introduce recent experimental results demonstrating
      that high crystallinity and specific molecular arrangements lead to
      crystallization-induced property changes. We believe that the understanding of
      the crystallization-induced property changes in organic crystals will provide
      both fundamental knowledge of the chemical processes occurring at various
      interfaces and opportunities for researchers to take advantage of crystallization
      induced property changes in the development of high-performance organic devices.

PMID- 24901374
TI  - Lutein and zeaxanthin toxicity with and without brilliant blue in rabbits.
AB  - PURPOSE: To evaluate the safety profile of solutions containing lutein and
      zeaxanthin alone or associated with brilliant blue (BB). METHODS: Twenty-eight
      New Zealand rabbits were used to evaluate 4 concentrations of the various dye
      solutions: 0.5% lutein/zeaxanthin; 0.5% lutein/zeaxanthin associated with 0.0125%
      BB; 0.3% lutein/zeaxanthin associated with 0.025% BB; and 0.25% lutein/zeaxanthin
      associated with 0.05% BB. The pHs of the dye solutions ranged from 6.5 to 7.2 and
      the osmolarities from 280 to 320 mOsm/mL. Each rabbit had 0.1 mL of one of the
      dyeing solutions injected into the vitreous cavity of the right eye, while
      balanced salt solution (BSS) was injected into the left eye as the control.
      Scotopic electroretinography responses were recorded in all eyes at different
      time points. The animals were sacrificed at 1 and 7 days after injection; the
      eyes were analyzed by light and transmission electron microscopy. RESULTS: No
      significant (P>0.05) differences were seen in the a- and b-wave amplitudes among
      groups at any given point in time. Light and electron microscopy findings showed
      no significant abnormalities either, and were similar to the histological
      findings after intravitreal BSS injection. CONCLUSIONS: Lutein and zeaxanthin
      alone or in association with BB showed a good safety profile in this experimental
      model.

PMID- 24901375
TI  - In vivo long-term magnetic resonance imaging activity of ferritin-based magnetic
      nanoparticles versus a standard contrast agent.
AB  - New long-circulating maghemite nanoparticles of 4 and 6 nm, coated with an
      apoferritin protein capsid, exhibit useful properties to act as magnetic
      resonance imaging (MRI) contrast agents. A full in vivo study of the so-called
      apomaghemites reveals that their long-term MRI properties are better than those
      of a standard superparamagnetic iron oxide (SPIO) widely used in biomedical
      applications. The biodistribution of apomaghemites and standard SPIO was
      investigated by MRI in mice at two different concentrations, 6 and 2.5 mg of
      Fe.kg(-1), over 60 days. Significant differences are found at low dose (2.5 mg of
      Fe.kg(-1)). Thus, whereas apomaghemites are active for MR bioimaging of liver for
      45 days, standard SPIO is not effective beyond 7 days. On the basis of our data,
      we may concluded that apomaghemites can act as new long-term MRI liver contrast
      agents, allowing first the diagnosis of a liver pathology and then monitoring
      after treatment without the need for a second injection.

PMID- 24901376
TI  - Octaarginine-modified liposomes enhance cross-presentation by promoting the C
      terminal trimming of antigen peptide.
AB  - Exogenous antigen proteolysis by proteasomes and amino peptidases is essential
      for the production of mature major histocompatibility complex class I (MHC-I)
      peptides to induce cross-presentation. We report here that when liposomes are
      modified with octaarginine (R8-Lip), a type of cell-penetrating peptide, the
      production of the mature MHC-I peptide is enhanced by promoting the C-terminal
      trimming of the antigen peptide. The efficiency of cross-presentation of
      ovalbumin (OVA) using the R8-Lip was dramatically higher than that by octalysine
      modified liposomes (K8-Lip) in mouse bone-marrow derived dendritic cells (BMDCs),
      although the physical characters of both liposomes were comparable. In this
      study, we investigated the mechanism responsible for the enhancement in cross
      presentation by R8-Lip. Although the efficiencies of cellular uptake, endosomal
      escape, proteolysis of OVA and DC maturation between the two systems were
      essentially the same, an analysis of peptide trimming to SIINFEKL (mature MHC-I
      peptide of OVA) by using R8-Lip and K8-Lip encapsulating peptides of various
      length clearly indicates that the use of R8-Lip enhances the efficiency of the C
      terminal cleavage of antigen-derived peptides. This finding provides a new
      strategy for achieving efficient cross-presentation by using R8 peptide and
      arginine-rich peptides. Moreover, this result may contribute to the development
      of a new paradigm regarding the machinery associated with antigen peptide
      production. 

PMID- 24901378
TI  - High-performance electrocatalysis using metallic cobalt pyrite (CoS2) micro- and
      nanostructures.
AB  - The development of efficient and robust earth-abundant electrocatalysts for the
      hydrogen evolution reaction (HER) is an ongoing challenge. We report metallic
      cobalt pyrite (cobalt disulfide, CoS2) as one such high-activity candidate
      material and demonstrate that its specific morphology--film, microwire, or
      nanowire, made available through controlled synthesis--plays a crucial role in
      determining its overall catalytic efficacy. The increase in effective electrode
      surface area that accompanies CoS2 micro- and nanostructuring substantially
      boosts its HER catalytic performance, with CoS2 nanowire electrodes achieving
      geometric current densities of -10 mA cm(-2) at overpotentials as low as -145 mV
      vs the reversible hydrogen electrode. Moreover, micro- and nanostructuring of the
      CoS2 material has the synergistic effect of increasing its operational stability,
      cyclability, and maximum achievable rate of hydrogen generation by promoting the
      release of evolved gas bubbles from the electrode surface. The benefits of
      catalyst micro- and nanostructuring are further demonstrated by the increased
      electrocatalytic activity of CoS2 nanowire electrodes over planar film electrodes
      toward polysulfide and triiodide reduction, which suggests a straightforward way
      to improve the performance of quantum dot- and dye-sensitized solar cells,
      respectively. Extension of this micro- and nanostructuring strategy to other
      earth-abundant materials could similarly enable inexpensive electrocatalysts that
      lack the high intrinsic activity of the noble metals.

PMID- 24901377
TI  - Infectious Complication Following Midface Reconstruction With Calcified
      Triglyceride.
AB  - This case report describes an infectious complication related to the use of
      calcified triglyceride (Kryptonite Bone Cement) in post-traumatic midface
      reconstruction. Ultimately, the infected material required removal, and the
      facial deformity was repaired with subsequent procedures. The literature suggests
      that bone cement products should be used with caution when in contact with the
      paranasal sinuses. 

PMID- 24901379
TI  - Methylmercury photodegradation in surface water of the Florida Everglades:
      importance of dissolved organic matter-methylmercury complexation.
AB  - Photodegradation is the major pathway of methylmercury (MeHg) degradation in many
      surface waters. However, the mechanism of MeHg photodegradation is still not
      completely understood. Dissolved organic matter (DOM) is expected to play a
      critical role in MeHg photodegradation. By using several techniques, including
      N2/O2 purging and the addition of stable isotope (Me(201)Hg), scavengers,
      competing ligands, and a singlet oxygen ((1)O2) generator, the role played by
      MeHg-DOM complexation in MeHg photodegradation of Everglades surface water was
      investigated. DOM appeared to be involved in MeHg photodegradation via the
      formation MeHg-DOM complexes based on three findings: (1) MeHg was quickly
      photodegraded in solutions containing DOM extracts; (2) degradation of MeHg did
      not occur in deionized water; and (3) addition of competing complexation reagents
      (dithiothreitol-DTT) dramatically prohibited the photodegradation of MeHg in
      Everglades water. Further experiments indicated that free radicals/reactive
      oxygen species, including hydroxyl radical (.OH), (1)O2, triplet excited state of
      DOM ((3)DOM*), and hydrated electron (e(-)aq), played a minor role in MeHg
      photodegradation in Everglades water, based on the results of scavenger addition,
      (1)O2 generator addition and N2/O2 purging. A pathway, involving direct
      photodegradation of MeHg-DOM complexes via intramolecular electron transfer, is
      proposed as the dominant mechanism for MeHg photodegradation in Everglades water.

PMID- 24901380
TI  - Hepatic metabolic response to restricted copper intake in a Niemann-Pick C murine
      model.
AB  - Niemann-Pick C disease (NPC) is a vesicular trafficking disorder primarily caused
      by mutations in the Npc1 gene and characterized by liver dysfunction and
      neuropathology. Altered hepatic copper metabolism has recently been reported in
      NPC disease. Therefore, we aimed to analyze the effects of a copper deficient
      diet and copper chelation using d-penicillamine on copper homeostasis in the
      liver of Npc1(-/-) mice of different ages. We examined liver metal ion content by
      AAS, and copper and iron metabolism gene expression in the liver using qPCR in
      Npc1(+/+) and Npc1(-/-) mice. We found higher copper and lower iron content in
      the liver of Npc1(-/-) mice of different ages, compared to controls; these
      changes in copper and iron content were correlated with increased ceruloplasmin,
      metallothionein 1, and transferrin receptor gene expression and decreased gene
      expression of Commd1, ferritin-light chain and ferroportin in the liver of Npc1(
      /-) mice of different ages. Npc1(-/-) mice responded to a copper-deficient diet
      with a decrease in copper content in the liver, bile and heart. These results
      correlated with a reduction in the hepatic expression of ceruloplasmin and
      metallothionein 1 during the first week of treatment. d-penicillamine revealed
      hepatic adaptive response and an improvement in hepatic function in Npc1(-/-)
      mice without any effect on neurological functions. Our results confirm that the
      NPC1 protein is required for copper and iron homeostasis. To our knowledge, this
      is the first report documenting the hepatic adaptive response to low-copper
      intake in a Npc1(-/-) mouse model. 

PMID- 24901381
TI  - Disaster relief activities of the Japan self-defense force following the Great
      East Japan Earthquake.
AB  - Cooperation between civilian and military forces, including the Japan Self
      Defense Force (JSDF), enabled wide-ranging disaster relief after the Great East
      Japan Earthquake. Nevertheless, many preventable fatalities occurred,
      particularly related to an inability to treat chronic disease, indicating the
      need to plan for the provision of long-term medical aid after natural disasters
      in stricken areas and evacuation shelters. To assist in this effort, this report
      (1) provides an overview of the consequences of the medical response to the Great
      East Japan Earthquake, the largest natural disaster ever to hit Japan, focusing
      on the role and actions of the JSDF; (2) discusses the lessons learned regarding
      the provision of medical aid and management by the JSDF after this disaster,
      looking at the special challenges of meeting the needs of a rapidly aging
      population in a disaster situation; and (3) provides recommendations for the
      development of strategies for the long-term medical aid and support after natural
      disasters, especially with regard to the demographics of the Japanese population.

PMID- 24901382
TI  - Efficacy, tolerability, and safety of hypnosis in adult irritable bowel syndrome:
      systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the efficacy, tolerability, and safety of hypnosis in adult
      irritable bowel syndrome by a meta-analysis of randomized controlled trials.
      METHODS: Studies were identified by a literature search of the databases Allied
      and Complementary Medicine Database, Central Register of Controlled Trials,
      Cumulative Index to Nursing and Allied Health Literature, PubMed, PsycINFO, and
      Scopus (from inception to June 30, 2013). Primary outcomes were adequate symptom
      relief, global gastrointestinal score, and safety. Summary relative risks (RRs)
      with number needed to treat (NNT) and standardized mean differences (SMDs) with
      95% confidence intervals (95% CIs) were calculated using random-effects models.
      RESULTS: Eight randomized controlled trials with a total of 464 patients and a
      median of 8.5 (7-12) hypnosis sessions over a median of 12 (5-12) weeks were
      included into the analysis. At the end of therapy, hypnosis was superior to
      control conditions in producing adequate symptom relief (RR, 1.69 [95% CI = 1.14
      2.51]; NNT, 5 [3-10]) and in reducing global gastrointestinal score (SMD, 0.32
      [95% CI = -0.56 to -0.08]). At long-term follow-up, hypnosis was superior to
      controls in adequate symptom relief (RR, 2.17 [95% CI = 1.22-3.87]; NNT, 3 [2
      10]), but not in reducing global gastrointestinal score (SMD, -0.57 [-1.40 to
      0.26]). One (0.4%) of 238 patients in the hypnosis group dropped out due to an
      adverse event (panic attack). CONCLUSION: This meta-analysis demonstrated that
      hypnosis was safe and provided long-term adequate symptom relief in 54% of
      patients with irritable bowel syndrome refractory to conventional therapy.

PMID- 24901384
TI  - Pathology quiz case 1.

PMID- 24901385
TI  - Pathology quiz case 2.

PMID- 24901383
TI  - The effects of erythropoietin on bacterial translocation and inflammation in rats
      with obstructive jaundice.
AB  - INTRODUCTION: Obstruction of the common bile duct is associated with hepatic
      paranchymal damage and increased susceptibility to subsequent bacterial
      infections. Erythropoietin has antiinflammatory and cytoprotective effects and it
      induces antiinflammatory cytokines and suppresses the production of
      proinflammatory cytokines. In this study, we aimed to investigate the effect of
      Erythropoietin on bacterial translocation, inflammation and tissue damage in rats
      with obstructive jaundice. MATERIALS AND METHODS: Thirty-two Wistar albino rats
      (200-250 g) were divided into 4 groups as follows: Group 1 (Sham); only
      hepatoduodenal ligament dissection, Group 2 (Erythropoietin); hepatoduodenal
      ligament dissection and given 500 IU/kg Erythropoietin subcutaneously, Group 3
      (Obstructive jaundice); complete hepatoduodenal ligament ligation, Group 4
      (Obstructive jaundice + Erythropoietin); complete hepatoduodenal ligament
      ligation and given 500 IU/kg Erythropoietin subcutaneously. After 7 days, the
      rats were sacrificed by taking blood from the heart for biochemical analyses.
      Peritoneal swab culture, liver, mesenteric lymph nodes, spleen and ileum were
      collected for microbiological and histopathological examinations. RESULTS:
      Erythropoietin reduced the secretion of inflammatory cytokines, oxidative damage
      and bacterial translocation, prevent the formation of inflammatory changes in
      intestine and liver after obstructive jaundice. CONCLUSION: The treatment of EPO
      in rats with OJ reduces bacterial translocation, inflammation and tissue damage.

PMID- 24901386
TI  - Characterization of first-time hospitalizations in patients with newly diagnosed
      pulmonary arterial hypertension in the REVEAL registry.
AB  - BACKGROUND: Hospitalization is an important outcome in pulmonary arterial
      hypertension (PAH), shown previously to correlate with survival. Using the
      Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL
      Registry), we sought to characterize first-time hospitalizations and their effect
      on subsequent hospitalization and survival in patients with newly diagnosed
      disease. METHODS: Patients with newly diagnosed PAH (n = 862, World Health
      Organization group 1) were evaluated for first-time hospitalization. The
      hospitalizations were categorized as PAH related or PAH unrelated based on the
      case report form. Categories for PAH-related and PAH-unrelated hospitalization
      were defined before independent review. Patient demographics and disease
      characteristics are described as well as freedom from hospitalization and
      survival. RESULTS: Of 862 patients, 490 (56.8%) had one or more hospitalizations
      postenrollment: 257 (52.4%) PAH related, 214 (43.7%) PAH unrelated, and 19 (3.9%)
      of undetermined causes. The most common causes of PAH-related hospitalization
      were congestive heart failure and placement/removal of a central venous catheter.
      Patients with PAH-related hospitalizations were more likely to receive parenteral
      therapy, be in functional class III/IV, and have higher risk scores before
      hospitalization at enrollment. Following discharge, 25.4% +/- 3.2% and 31.0% +/-
      4.0% of patients with PAH-related and PAH-unrelated first hospitalization,
      respectively, remained hospitalization-free for 3 years (P = .11). Survival
      estimates at 3 years postdischarge were 56.8% +/- 3.5% and 67.8% +/- 3.6% (P =
      .037) for patients with PAH-related and PAH-unrelated hospitalization,
      respectively. CONCLUSIONS: In the REVEAL Registry, PAH-related hospitalization
      was associated with relatively more rehospitalizations and worse survival at 3
      years. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL:
      www.clinicaltrials.gov.

PMID- 24901387
TI  - Enhanced in vivo targeting of murine nonparenchymal liver cells with
      monophosphoryl lipid A functionalized microcapsules.
AB  - A broad spectrum of infectious liver diseases emphasizes the need of
      microparticles for targeted delivery of immunomodulatory substances to the liver.
      Microcapsules (MCs) are particularly attractive for innovative drug and vaccine
      formulations, enabling the combination of antigen, drugs, and adjuvants. The
      present study aimed to develop microcapsules characterized by an enhanced liver
      deposition and accelerated uptake by nonparenchymal liver cells (NPCs).
      Initially, two formulations of biodegradable microcapsules were synthesized from
      either hydroxyethyl starch (HES) or mannose. Notably, HES-MCs accumulated
      primarily in the liver, while mannose particles displayed a lung preference.
      Functionalization of HES-MCs with anti-CD40, anti-DEC205, and/or monophosphoryl
      lipid A (MPLA) enhanced uptake of MCs by nonparenchymal liver cells in vitro. In
      contrast, only MPLA-coated HES-MCs promoted significantly the in vivo uptake by
      NPCs. Finally, HES-MCs equipped with MPLA, anti-CD40, and anti-DEC205 induced the
      secretion of TNF-alpha, IL-6 by Kupffer cells (KCs), and IFN-gamma and IL-12p70
      by liver dendritic cells (DCs). The enhanced uptake and activation of KCs by MPLA
      HES-MCs is a promising approach to prevent or treat infection, since KCs are
      exploited as an entry gate in various infectious diseases, such as malaria. In
      parallel, loading and activating liver DCs, usually prone to tolerance, bears the
      potential to induce antigen specific, intrahepatic immune responses necessary to
      prevent and treat infections affecting the liver. 

PMID- 24901388
TI  - Triflic acid promoted direct alpha-alkylation of unactivated ketones using
      benzylic alcohols via in situ formed acetals.
AB  - Direct alpha-alkylation of unactivated ketones using benzylic alcohols as
      electrophiles has been achieved at room temperature. This reaction takes place
      via in situ formed acetal using triflic acid and trimethyl orthoformate. It is
      believed that methyl vinyl ether formed from the in situ generated dimethyl
      acetal in the presence of triflic acid undergoes alkylation. Diverse ketones
      could be alkylated with diarylmethanols, cinnamyl alcohols, and phenyl propargyl
      alcohols having different electrophilicities. 

PMID- 24901389
TI  - Comparison of the CLSI guideline and ISO/IDF standard for antimicrobial
      susceptibility testing of Lactobacilli.
AB  - Lactobacilli play a crucial role as probiotics and as starter cultures in the
      production of fermented foods. Although lactobacilli are a technologically useful
      and beneficial group of bacteria, a few members of them have been rarely
      correlated with bacterial infections. Correspondingly, clinicians are interested
      in the antimicrobial susceptibility of lactobacilli. In addition, antimicrobial
      susceptibility testing (AST) is also relevant for commercially applied
      lactobacilli as bacterial strains harboring transferable antibiotic resistance
      genes should not be used in fermented and probiotic foods. Therefore, two methods
      were developed by different organizations, which were compared within this study.
      For this purpose, 22 Lactobacillus-type strains were tested for their
      antimicrobial susceptibility to 16 antibiotics following the procedures of the
      Clinical and Laboratory Standards Institute (CLSI) and the International
      Organization of Standardization (ISO)/International Dairy Federation (IDF).
      Crucial discrepancies between both procedures were detected mainly due to the
      different AST media. Hence, half of the strains tested did not consistently grow
      in the CLSI medium, whereas all showed evaluable growth in the ISO/IDF medium.
      However, some antibiotics were influenced by the latter medium. In particular,
      low levels of essential agreement between both methods were obtained with seven
      antibiotics. Accordingly, different interpretative criteria are needed for both
      procedures to distinguish resistant from susceptible strains. 

PMID- 24901390
TI  - Selected topics in gynecologic pathology honoring Robert E. Scully, M.D. His life
      and legacy.

PMID- 24901391
TI  - A tribute to Robert E. Scully, M.D.

PMID- 24901392
TI  - Pseudoneoplastic glandular lesions of the uterine cervix: a selective review.
AB  - Pseudoneoplastic glandular lesions of the cervix continue to be diagnostically
      challenging for the surgical pathologist. This review covers a select number of
      these lesions that may be misinterpreted as premalignant or malignant, with an
      emphasis on those about which Dr Scully has advanced our knowledge. The topics
      covered include microglandular hyperplasia, mesonephric hyperplasia, diffuse
      laminar endocervical glandular hyperplasia, lobular endocervical glandular
      hyperplasia, and endocervical adenomyoma. The first listed entity has a greater
      diversity of morphology than the name might imply including, but not limited to
      solid growth and prominent hyaline stroma. The second entity may be remarkably
      diffuse within the cervical wall and reasonably result in consideration of
      diagnoses such as minimal deviation adenocarcinoma (adenoma malignum), but has
      nonmucinous epithelium and bland cytology. The third entity, one of the least
      common of those considered, represents a peculiar form of reactive hyperplasia of
      the endocervical epithelium. The fourth entity is the one about which knowledge
      is still fast advancing. In pure form with no atypia it is almost certainly a
      clinically benign process, but a subset of cases show cytologic atypia and an
      occasional association with adenocarcinoma is seen. Finally, adenomyomas of the
      uterus in general have received much attention in recent years, mostly in the
      corpus, but the less common endocervical variant may be particularly problematic
      because mucinous epithelium in abundant myogenic stroma may be potentially
      confused with an infiltrating differentiated mucinous adenocarcinoma. Although
      immunohistochemistry may play a role on occasion in evaluating benign
      endocervical glandular proliferations the mainstay of their interpretation
      remains conventional morphologic analysis of routinely stained slides. 

PMID- 24901394
TI  - Low-grade serous tumors of ovary.
AB  - The creation of the category of borderline/atypical proliferative tumors in the
      World Health Organization Classification of Ovarian Tumors in 1973 prompted
      extensive investigation of the clinicopathologic and genetic features of low
      grade serous ovarian tumors (borderline tumors/atypical proliferative tumors,
      noninvasive micropapillary tumors, and invasive low-grade serous carcinomas). The
      clinicopathologic studies of these tumors resulted in clarification of the
      prognostic significance of several histologic features of the ovarian tumors and
      their associated peritoneal lesions. The genetic studies resulted in a
      reassessment of the relationship between low-grade and high-grade serous
      carcinoma and their differing pathways of origin. This review focuses on several
      of the morphologic findings, their diagnostic criteria, differential diagnosis
      and biologic significance, and discusses the dualistic classification of serous
      carcinomas into high-grade and low-grade tumors. 

PMID- 24901393
TI  - Discovery of a cell: reflections on the checkered history of intermediate
      trophoblast and update on its nature and pathologic manifestations.
AB  - In 1976, a series of 12 cases describing a lesion that had previously not been
      well characterized was reported as "trophoblastic pseudotumor of the uterus." Up
      until that time rare reports of the lesion had classified it most often as an
      unusual type of sarcoma associated with pregnancy. All patients in that series
      were alive and well except for one who died from complications of a uterine
      perforation occurring at the time of a diagnostic curettage. Thus, it appeared to
      be a benign neoplasm but subsequently it was found that some exhibited malignant
      behavior and the tumor was renamed "placental site trophoblastic tumor." A
      variety of observations pointed to an origin in a distinctive cell of the
      placental site, designated "intermediate trophoblast," which physiologically is
      seen in the normal implantation site. Subsequently, another subset of
      intermediate trophoblast cells originating from the chorion laeve have been shown
      to give rise to the placental site nodule/plaque, a well-circumscribed and
      usually microscopic incidental finding as well as the epithelioid trophoblastic
      tumor, its putative malignant counterpart. The initial description of
      "trophoblastic pseudotumor" opened a new area of research which brought to bear
      immunohistochemical and molecular genetic analyses that eventually has led to new
      insights in the diverse morphologic changes occurring in early placentation and
      also led to the development of a new classification of trophoblastic tumors and
      tumor-like lesions. 

PMID- 24901395
TI  - Unusual patterns of endometrial carcinoma including MELF and its relation to
      epithelial mesenchymal transition.
AB  - Although most of Dr Scully's research addressed diseases of the ovary, about 10%
      of his published manuscripts focused on endometrial lesions, most often
      consisting of observations about unusual types or deceptive patterns of
      endometrial carcinoma that had not previously been described, or lesions for
      which the behavior had been unknown. He characterized and clarified the entity of
      clear cell carcinoma of the endometrium, and wrote about endometrial carcinomas
      with argyrophil, oxyphil, and giant cells, and those simulating microglandular
      hyperplasia of the cervix, as well as uterine papillary serous, squamous cell,
      and small cell carcinoma,. He provided a useful classification of precancers of
      the endometrium and also emphasized the relationship between estrogens and the
      development of some forms of uterine carcinoma. This article addresses the
      importance of his careful observations, focusing primarily on the potential
      relationship of 1 pattern of endometrial carcinoma that he described which has
      areas of microcystic, elongated, fragmented glands (MELF), frequently accompanied
      by a fibromyxoid or inflammatory stroma, to the recently described concept of
      epithelial mesenchymal transition. Endometrioid carcinomas with MELF frequently
      display a variety of immunohistochemical changes including reduced expression of
      E-cadherin, B-catenin, estrogen and progesterone receptors, Ki67, and
      overexpression of fascin, galactin-3, cyclin D1, and p16, as might be expected
      with epithelial mesenchymal transition. Additional studies will be needed to
      explain the significance of epithelial mesenchymal transition that occurs in
      carcinomas with regions of MELF. 

PMID- 24901396
TI  - Gonadoblastoma and hepatoid and endometrioid-like yolk sac tumor: an update.
AB  - Dr Robert E. Scully greatly advanced our understanding of germ cell neoplasia to
      the extent that it is difficult to narrow the discussion of his contributions to
      this topic so that it can be covered in a brief article. This article accordingly
      focuses on some of the recent developments concerning 2 of his major
      contributions in this area-the gonadoblastoma (GB) and variant morphologies of
      yolk sac tumor. GB was defined by Dr Scully in 1953 and its features elaborated
      in detail by him in 1970. This neoplasm occurred in young patients who often
      displayed phenotypic sex ambiguities and frequently presented with primary
      amenorrhea. It was bilateral in 40%, and consisted of circumscribed nests of
      small sex cord cells and germinoma-like cells admixed with round deposits of
      eosinophilic, hyaline, often calcified material. These nests were set in a
      spindle cell gonadal stroma with Leydig-like or lutein-like cells. Because of his
      work we now understand that this precursor to invasive germ cell tumors occurs in
      patients with a specific form of disorder of sex development, namely gonadal
      dysgenesis, and only in those who have a particular portion of the Y chromosome,
      the GB locus/TSPY gene, within the gonadal tissue. An essential element to the
      development of GB appears to be a defect in the genetic pathway that leads to the
      development of Sertoli cells. Improperly formed Sertoli cells predispose to
      "delayed maturation" of the gonocytes of the gonad and predispose them to undergo
      malignant transformation. "Undifferentiated gonadal tissue" has been proposed as
      the precursor to the development of GB and consists of an unorganized mixture of
      apparently non-neoplastic germ cells, germ cells with delayed maturation, and
      neoplastic germ cells with sex cord cells and gonadal stroma. Two variant
      morphologies of yolk sac tumor were also recognized by Dr Scully. In the hepatoid
      variant features similar to hepatocellular carcinoma occurred, although primitive
      glandular foci and lack of liver involvement permitted its distinction in most
      cases. More recently this variant has been found to occasionally produce bile in
      canalicular-like structures and to stain strongly for both SALL4 and glypican 3,
      2 recently described markers of yolk sac tumor. Recognition of hepatoid yolk sac
      tumor was followed by the description of a potential mimic, primary ovarian
      hepatoid carcinoma, which, however, occurred in a significantly older patient
      population and was occasionally associated with surface epithelial neoplasia. The
      endometrioid-like variant of yolk sac tumor simulated primary endometrioid
      adenocarcinoma. It can be suspected on routine stains because of primitive
      appearing nuclei, frequent subnuclear vacuoles, and in some cases association
      with more usual yolk sac tumor. Its recognition is now facilitated by a panel of
      immunohistochemical stains that are often expressed differentially in these 2
      neoplasms--endometrioid-like yolk sac tumor: positive for SALL4, glypican 3, and
      alpha-fetoprotein; endometrioid adenocarcinoma: positive for cytokeratin 7 and
      epithelial membrane antigen. Finally, Dr Scully contributed one of the first
      cases in the literature of yet another nuance in the complicated world of yolk
      sac neoplasia, namely the development of some tumors on the background of a
      surface epithelial neoplasm. This is analogous to the more common development of
      choriocarcinoma from carcinoma and, in the case of yolk sac tumor, diagnosis is
      aided clinically by the usual older age of the patient and nature of the
      associated neoplasia.

PMID- 24901397
TI  - Cellular mesenchymal tumors of the uterus: a review emphasizing recent
      observations.
AB  - Cellular mesenchymal tumors of the uterus may be divided in 2 main groups, smooth
      muscle and endometrial stromal. Among the former, highly cellular leiomyoma is
      the classic example. This tumor is not infrequently confused with an endometrial
      stromal tumor due to its often yellow color and soft consistency, dense
      cellularity, striking vascularity, not uncommon irregular margin and even rarely
      association with seedling cellular leiomyomas, both mimicking the infiltration of
      a low-grade endometrial stromal sarcoma. Cellular intravenous leiomyomatosis can
      also mimic endometrial stromal sarcoma due to their shared intravascular growth.
      A variety of histologic features typical of cellular smooth muscle including
      clefts and differing vasculature help in this distinction. Although endometrial
      stromal tumors are typically highly cellular, recent studies have expanded their
      spectrum to include those that are less so due to smooth muscle metaplasia,
      fibrous and myxoid change, and even oxyphilic cytoplasm. A subset now designated
      high-grade endometrial stromal sarcoma showing a t(10;17) has been characterized
      to show small epithelioid cells associated with brisk miotic activity, typically
      being CD10, ER and PR negative, and cyclin D1 positive. These tumors are
      juxtaposed to areas of fibromyxoid endometrial stromal neoplasia in 50% of cases.
      An enigmatic category of uterine mesenchymal neoplasms, often densely cellular,
      are those descriptively referred to as "uterine tumors resembling ovarian sex
      cord tumors." Their spectrum is briefly noted as is their crucial distinction
      from stromal sarcoma with sex cord-like differentiation. Other tumors that rarely
      occur in the uterus that are densely cellular include but are not limited to
      undifferentiated uterine sarcoma, embryonal rhabdomyosarcoma, primitive
      neuroectodermal tumor, lymphoma or small cell, or undifferentiated carcinoma. In
      this essay, I review the most helpful morphologic, immunohistochemical, and/or
      cytogenetic features in the diagnosis of each one of these entities. 

PMID- 24901398
TI  - A small organ takes center stage: selected topics in fallopian tube pathology.
AB  - In this paper we consider a number of non-neoplastic and neoplastic lesions of
      the fallopian tube. Emphasis has been placed on diagnostically difficult
      entities, some of which result in misdiagnosis and consequent alteration of
      treatment, including "pseudocarcinomas" that represent a florid epithelial
      response to acute and/or chronic salpingitis. Endometriosis-related lesions may
      cause infertility, or undergo malignant transformation to a Mullerian carcinoma,
      most frequently endometrioid and clear cell types. Pregnancy-related tubal
      lesions include the easily misdiagnosed metaplastic papillary tumor as well as
      several manifestations of ectopic pregnancy. Covered briefly are familial
      conditions such as the Peutz-Jeghers syndrome and its association with tubal
      mucinous metaplasia, clear cell papillary cystadenoma associated with von Hippel
      Lindau syndrome, and the Li Fraumeni syndrome's germline p53 mutation and its
      association with distal tubal p53 signatures. Miscellaneous tumors discussed
      include the common adenomatoid tumor and the uncommon female adnexal tumor of
      probable Wolffian origin. Important issues including the updated staging of
      fallopian tube carcinomas, and the histopathologic variants of endometrioid
      carcinomas and their sometimes unusual patterns that engender the potential for
      confusion with other tumors are briefly noted. The final section covers the
      relatively recent and novel concept of the fallopian tube as the predominant site
      of origin of ovarian and peritoneal carcinomas. Discussed are the histologic,
      immunohistochemical, and molecular biologic evidence that support the tubal
      fimbria as the site of serous tubal intraepithelial carcinoma, possibly the
      immediate precursor to high-grade ovarian and peritoneal serous carcinoma. 

PMID- 24901399
TI  - Selected topics in peritoneal pathology.
AB  - This essay considers selected peritoneal lesions many of which were the subject
      of studies coauthored by Dr Robert E. Scully. His article on multilocular
      peritoneal inclusion cysts has largely led to these lesions being considered non
      neoplastic, eschewing the term cystic mesothelioma. These cysts are often
      associated with reactive mural mesothelial proliferations that can potentially
      lead to a misdiagnosis of mesothelioma. Clinical findings, such as a common
      association with endometriosis or prior operations, can prompt consideration of a
      reactive lesion. Mesothelial hyperplasia may be difficult to distinguish, when
      florid, from mesothelioma but a variety of gross and microscopic features will
      aid their recognition. Nodular peritoneal aggregates of histiocytes (sometimes
      admixed with mesothelial cells) may occasionally be a striking finding that can
      be misdiagnosed as a metastasis if the patient has a known neoplasm. Appreciation
      of their bland nuclear features and histiocytic nature, confirmed by
      immunohistochemical markers, facilitate the diagnosis. Various forms of
      peritonitis are briefly considered including sclerosing peritonitis, a process
      sometimes associated with luteinized thecomas (thecomatosis) of the ovaries, an
      entity first appreciated by Dr Scully. Mesotheliomas are briefly reviewed
      emphasizing the caution that should be used in applying the designation "well
      differentiated papillary mesothelioma." Many interpret the latter as benign, but
      multifocal lesions must be thoroughly examined histologically because of
      potential overlapping features with malignant mesothelioma. The morphologic
      spectrum of malignant mesothelioma and its usually straightforward distinction
      from mullerian neoplasms is considered, as is its occasional presentation as a
      dominant ovarian mass. The spectrum of low-grade serous peritoneal neoplasms
      including the "psammocarcinoma" is reviewed. Finally, various benign mullerian
      lesions, particularly endometriosis and endosalpingiosis, may be conspicuous in
      peritoneal specimens and sometimes are grossly striking. The usual presence of
      benign endometrioid epithelium and stroma should facilitate the correct diagnosis
      of endometriosis, but in cases in which the stroma is atrophic or the sole
      component (stromal endometriosis), diagnostic problems may arise. 

PMID- 24901401
TI  - The expression of Cox-2, NF-kappaB, and VEGF in ectopic endometrial tissues
      within fallopian tubes suggests different etiologies.
AB  - The ectopic endometrial tissues lining the lumen of the fallopian tubes are
      currently defined as either "endometrial colonization" or "endometriosis" on the
      basis of their location within or beyond the isthmic portion of the fallopian
      tubes. The underlying etiology is unclear. The goal of this study was to define
      the fallopian endometrial lesions pathogenetically rather than anatomically. We
      investigated 39 cases of the ectopic endometrial tissues within the fallopian
      tubes, most of which exceeded the isthmus. Immunohistochemical analysis was
      performed to evaluate the expression of Cox-2, NF-kappaB, and VEGF, which are
      specifically expressed by classic endometriosis. Other clinicopathologic
      parameters were also recorded. The results indicated that the lesions that were
      confined to the mucosa might differ from those observed in the muscular or
      serosal layers, which showed significantly less surrounding inflammatory reaction
      and less concurrent salpingitis and other endometriotic lesions. The expression
      of Cox-2, NF-kappaB, and VEGF of the ectopic endometrial stromal cells tended to
      increase in the progression from the inner to the outer part of the tubes with
      significance. The expression of NF-kappaB and VEGF correlates with the
      microscopic findings of inflammation. Sterilization by tubal ligation exhibited a
      unique pattern of distribution. Except in those patients with tubal ligation,
      considering the different expression patterns observed in the tubal ectopic
      endometrial lesions, the mucosal type should be diagnosed as "endometrial
      colonization" wherever the lesion occurs. The others should be diagnosed as
      "endometriosis" to reveal the etiology identical to typical endometriotic
      lesions. 

PMID- 24901400
TI  - High incidence of ErbB3, ErbB4, and MET expression in ovarian cancer.
AB  - Ovarian cancer is the leading cause of death from gynecologic cancers in the
      United States. Failure may be due to variable expression and/or complex
      interactions of growth factor receptors in individual tumors. As ErbB3-MET
      cooperativity is implicated in solid tumor resistance to EGFR/ErbB2 inhibitors,
      we evaluated expression of MET and all 4 ErbB family members in ovarian cancers.
      Tissue arrays were prepared from archival formalin-fixed paraffin-embedded tumor
      samples, including 202 ovarian carcinomas (Stage I-IV) and controls. Of 202
      patient samples, only 25% were positive for EGFR and 35% for ErbB2 expression.
      ErbB3, ErbB4, and MET showed marked expression in 76%, 98%, and 96% of cases.
      Consistent with high incidence, there was no significant correlation for
      expression of ErbB3, ErbB4, or MET with outcome. On the basis of their high
      expression in the majority of cases, inhibitors targeting ErbB3, ErbB4, and/or
      MET may be broadly applicable as therapeutic agents in this disease. 

PMID- 24901402
TI  - Massive ovarian edema associated with a broad ligament leiomyoma: a case report
      and review.
AB  - Massive ovarian edema is a rare disorder in which there is marked accumulation of
      interstitial fluid in the stroma of the ovary. Grossly, the involved ovary is an
      enlarged solid mass with a smooth tan-white surface, easily confused with a
      neoplasm. Microscopically, it features diffuse interstitial edema sparing
      follicles and outer cortex, dilated lymphatic vessels, thick-walled veins,
      fibromatosis, and luteinized stromal cells. It is believed that massive ovarian
      edema arises from interference in lymphatic drainage and venous return of the
      ovary secondary to partial torsion among other etiologies. Herein we provide the
      first description of unilateral ovarian edema in association with a large
      leiomyoma in the ipsilateral broad ligament. It is important to recognize the
      various presentations of this benign entity and to consider it in the
      differential diagnosis of an adnexal mass in a reproductive age woman. 

PMID- 24901403
TI  - Displaced granulosa cells within the ovarian stroma in a BRCA1 mutation carrier.

PMID- 24901404
TI  - PAX8 expression in uterine malignant mesodermal mixed tumor (carcinosarcoma).
AB  - PAX8 has emerged as a useful immunohistochemical marker for epithelial neoplasms
      of gynecologic origin. Expression of PAX8 in uterine malignant mesodermal mixed
      tumors (MMMT, carcinosarcoma) has not been characterized in detail. The goal of
      this study is to evaluate PAX8 expression in uterine MMMTs, with particular
      attention to its distribution in specific tumor components. Thirty-seven cases
      were studied. PAX8 expression was assessed by immunohistochemistry and scored
      separately in the epithelial and mesenchymal components of the tumors. The extent
      of staining was scored based on the estimated percentage of positive tumor cells
      as 1+: 1% to 25%; 2+: 26% to 50%; 3+: 51% to 75%; 4+: 76% to 100%. The epithelial
      component expressed PAX8 in all but 1 tumor, with 92% of tumors displaying 3+ and
      4+ extent of staining. The mesenchymal component lacked PAX8 expression in 27
      cases (73%) with variable expression in the remaining 10 cases. In addition, 12
      tumors contained undifferentiated areas that were not readily classifiable as
      carcinoma or sarcoma based on morphologic features. Of these, 8 (67%) were
      negative for PAX8, whereas 4 (33%) demonstrated variable extent of expression.
      Thus, PAX8 is expressed in the carcinomatous components of nearly all uterine
      MMMTs (97%), with expression in sarcomatous and undifferentiated components being
      less common and less extensive. The uniform, extensive expression in the
      carcinomatous components makes PAX8 a useful marker for diagnosis of
      carcinomatous metastases of uterine MMMT at extrauterine sites. Its infrequent
      expression in the sarcomatous and undifferentiated components limits its utility
      in identifying sarcoma-predominant metastases as gynecologic in origin. 

PMID- 24901405
TI  - Uterine Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy).
AB  - We report a unique case of Rosai-Dorfman disease (sinus histiocytosis with
      massive lymphadenopathy) involving the uterus. A 63-yr-old female with a history
      of parathyroid adenoma and cavernous sinus meningioma underwent total abdominal
      hysterectomy for a possible uterine malignancy. The histologic findings consisted
      of a nodular, mass-like infiltration of the myometrium by clusters, cords, and
      sheets of CD163-positve, S100-positive histiocytes with lymphocytophagocytosis
      (emperipolesis). The cells were negative for CD1a and langerin. Occasional plasma
      cells and erythrocytes were also present. Most of the histiocytes had pale,
      vacuolated, or foamy cytoplasm. In all cases, the nuclei were small and
      eccentric. No mitotic figures were identified. Two prior cases of Rosai-Dorfman
      disease have been reported in the female genital tract: 1 in the cervix and 1 in
      the bilateral ovaries. Rosai-Dorfman disease should be added to the differential
      diagnosis of histiocyte-rich lesions in the female genital tract. The diagnosis
      should be strongly considered in the presence of the characteristic histology
      with lymphocytophagocytosis (emperipolesis). A limited immunohistochemical panel
      consisting of CD163, S100, and CD1a and/or langerin will confirm the diagnosis in
      most cases. 

PMID- 24901406
TI  - Sebaceous hyperplasia of the vulva: a series of cases reporting no association
      with the Muir-Torre syndrome.
AB  - Sebaceous gland hyperplasia is a common skin condition, very rarely reported in
      the female genital region. We present 13 cases from 12 patients, the first case
      series of sebaceous gland hyperplasia of the vulva. Differences in age at
      presentation and clinical presentation compared with classic sebaceous gland
      hyperplasia from the head and neck region were noted. Also, it was rarely
      included in the clinical differential diagnosis. Immunohistochemical studies to
      determine any possible association with the Muir-Torre syndrome were performed
      and mismatch repair protein loss was not identified. 

PMID- 24901407
TI  - Fallopian tube high-grade serous carcinoma with intramucosal spread and
      presenting as a malignancy on pap smear.
AB  - For the first time, we report a case of a primary high-grade serous carcinoma of
      the fallopian tube in a 69-yr-old woman with intraepithelial involvement of
      endocervical glands. The patient had a remote history of tubal ligation and no
      known personal or family history of breast or gynecologic cancer. She initially
      presented with an abnormal Pap smear, and, on a subsequent endometrial curettage,
      detached fragments of high-grade adenocarcinoma were identified. Upon
      hysterectomy and bilateral salpingoophorectomy, invasive high-grade serous
      carcinoma was found in the proximal stump of a ligated fallopian tube.
      Morphologically identical tumor extensively involved the endocervical glands. A
      single focus of malignant cells was also found at the surface of the lower
      uterine segment endometrium. By immunohistochemistry, the tumors in the fallopian
      tube and in the cervix showed the same immunopheonotype. This included diffuse
      staining for WT-1, PAX-8, p16, and p53, and focal staining for the monoclonal
      carcinoembryonic antigen. The estrogen receptor was negative. Human
      papillomavirus-in situ hybridization was also negative. The focus of intramucosal
      tumor within the endometrium was similarly positive for WT-1 and p53 and negative
      for the estrogen receptor. The patient was subsequently treated with 6 cycles of
      carboplatinum and taxol. She remains well with no evidence of recurrent disease.
      The phenomenon of intramucosal tumor spread to the cervix mimicking primary
      invasive or in situ cervical adenocarcinoma may present a diagnostic challenge
      for the pathologist, requiring consideration of an appropriately wide
      differential diagnosis when interpreting cervical cytology and endocervical and
      endometrial biopsies. 

PMID- 24901408
TI  - Simple and sensitive analysis of histamine and tyramine in Japanese soy sauces
      and their intermediates using the stable isotope dilution HILIC-MS/MS method.
AB  - We established a simple, sensitive, and reproducible method to analyze the
      histamine and tyramine levels in Japanese soy sauce and its mash (called moromi)
      using hydrophilic interaction liquid chromatography with tandem mass spectrometry
      (HILIC-MS/MS). Histamine and tyramine quantification was performed using their
      stable isotopes for electrospray ionization-tandem mass spectrometry in the
      selected reaction monitoring mode. The sample pretreatment process was a simple,
      one-step liquid-liquid extraction. HILIC separation was performed with a gradient
      elution of aqueous ammonium formate and acetonitrile. Because of validation
      tests, the linearity, the accuracies, and precisions were sufficient. The limit
      of detection and the limit of quantification were 0.09 and 0.29 ppm for histamine
      and 0.13 and 0.42 ppm for tyramine, respectively. We successfully applied this
      method to histamine and tyramine determination in four kinds of commercial
      Japanese soy sauces and also in moromi samples during soy sauce production. 

PMID- 24901409
TI  - Update on the Guytonian view of hypertension.
AB  - PURPOSE OF REVIEW: Dr Arthur Guyton hypothesized that the capacity of the kidney
      to excrete sodium ultimately dictates long-term changes in blood pressure. This
      model has had a profound influence on our understanding of blood pressure
      regulation. The goal of this article is to review a selection of classic studies
      and highlight more recent molecular studies supporting or refuting the Guyton
      model of blood pressure regulation. RECENT FINDINGS: Molecular characterizations
      of human disorders of sodium homeostasis and blood pressure, and phenotypic
      analysis of transgenic mouse models, strongly support the Guytonian view that the
      kidney plays a central role in blood pressure control. However, recent studies
      also support the view that primary changes in the vasculature and nervous system
      significantly contribute to long-term changes in blood pressure. SUMMARY: The
      findings from provocative studies, particularly those that demonstrate how
      primary changes in the vasculature alter blood pressure without affecting renal
      sodium handling, challenge the Guyton model and need to be reconciled with the
      basic tenets of this model. Future characterization of these exceptions to the
      Guyton model will be critical in gaining a more complete understanding of the
      physiology of blood pressure regulation. This path of discovery will undoubtedly
      lead to new approaches for the diagnosis and treatment of hypertension.

PMID- 24901411
TI  - Well-defined transition metal hydrides in catalytic isomerizations.
AB  - This Feature Article intends to provide an overview of a variety of catalytic
      isomerization reactions that have been performed using well-defined transition
      metal hydride precatalysts. A particular emphasis is placed on the underlying
      mechanistic features of the transformations discussed. These have been
      categorized depending upon the nature of the substrate and in most cases
      discussed following a chronological order. 

PMID- 24901412
TI  - Nutrition and Gaelic football: review, recommendations, and future
      considerations.
AB  - Gaelic football is the second most popular team sport in Ireland in terms of
      participation. However, very little research exists on the nutritional
      considerations for elite male Gaelic footballers. Gaelic football is an
      intermittent type field game played by two teams of fifteen players. Although
      amateurs, elite players may train and compete 4-5 times per week and may play for
      several teams. Research suggests that elite footballers are similar
      anthropometrically and in fitness to professional soccer players. Work-rate
      analysis shows that footballers experience longer durations of high-intensity
      (HI) activity (5-7s) and shorter rest durations than soccer players. Recent data
      suggests that half-forward/backs perform a greater amount of HI work during games
      than players in other positions. Fatigue is apparent between the first and second
      halves and the first and fourth quarters. The limited amount of nutritional
      studies conducted implies that footballers may be deficient in energy intake and
      may be at the lower end of recommended carbohydrate intakes to support training.
      A wide variety of sweat rates have been measured during training, demonstrating
      the importance of individual hydration strategies. Ergogenic aids such as
      creatine and caffeine may prove beneficial to performance, although data are
      extrapolated from other sports. Due to the lack of research in Gaelic football,
      further population specific studies are required. Future areas of research on the
      impact of nutrition on Gaelic football performance are examined. In particular,
      the creation of a test protocol mimicking the activity patterns and intensity of
      a Gaelic football game is warranted. 

PMID- 24901413
TI  - How to reduce the latent social risk of disease: the determinants of vaccination
      against rabies in Taiwan.
AB  - To control the latent social risk of disease, the government usually spreads
      accurate information and attempts to improve the public's attitude toward
      adopting prevention. However, these methods with the Knowledge, Attitudes, and
      Practices (KAP) model do not always work. Therefore, we used the theory of
      planned behavior (TPB) to understand dog owners' behavior and distinguished the
      knowledge effect as objective knowledge (OK) and subjective knowledge (SK). A
      total of 310 dog owners completed a questionnaire based on our model. We employed
      structural equation modeling to verify the structural relationships and found
      three main results. First, our model was fit, and each path was significant.
      People with better attitudes, stronger subjective norms, and more perceptive
      behavioral control have stronger behavioral intention. Second, perceived
      behavioral control, not attitude, was the best predictive index in this model.
      Finally, on perceived behavioral control, subjective knowledge showed more
      influence than objective knowledge. We successfully extended TPB to explain the
      behavioral intention of dog owners and presented more workable recommendations.
      To reduce the latent social risk of disease, the government should not only
      address dog owners' attitudes, but also their subjective norms and perceptive
      behavioral control. Indeed, perceptive behavioral control and SK showed the most
      influence in this model. It is implied that the self-efficacy of dog owners is
      the most important factor in such a behavior. Therefore, the government should
      focus on enhancing dog owners' self-efficacy first while devoted to prevention
      activities. 

PMID- 24901415
TI  - Regarding "Impact of transthoracic endoscopic sympathectomy on plantar
      hyperhidrosis".

PMID- 24901414
TI  - Differential effects of antidepressant drugs on mTOR signalling in rat
      hippocampal neurons.
AB  - Recent studies suggest that ketamine produces antidepressant actions via
      stimulation of mammalian target of rapamycin (mTOR), leading to increased levels
      of synaptic proteins in the prefrontal cortex. Thus, mTOR activation may be
      related to antidepressant action. However, the mTOR signalling underlying
      antidepressant drug action has not been well investigated. The aim of the present
      study was to determine whether alterations in mTOR signalling were observed
      following treatment with antidepressant drugs, using ketamine as a positive
      control. Using Western blotting, we measured changes in the mTOR-mediated
      proteins and synaptic proteins in rat hippocampal cultures. Dendritic outgrowth
      was determined by neurite assay. Our findings demonstrated that escitalopram,
      paroxetine and tranylcypromine significantly increased levels of phospho-mTOR and
      its down-stream regulators (phospho-4E-BP-1 and phospho-p70S6K); fluoxetine,
      sertraline and imipramine had no effect. All drugs tested increased up-stream
      regulators (phospho-Akt and phospho-ERK) levels. Increased phospho-mTOR induced
      by escitalopram, paroxetine or tranylcypromine was significantly blocked in the
      presence of specific PI3K, MEK or mTOR inhibitors, respectively. All drugs tested
      also increased hippocampal dendritic outgrowth and synaptic proteins levels. The
      mTOR inhibitor, rapamycin, significantly blocked these effects on escitalopram,
      paroxetine and tranylcypromine whereas fluoxetine, sertraline and imipramine
      effects were not affected. The effects of escitalopram, paroxetine and
      tranylcypromine paralleled those of ketamine. This study presents novel in vitro
      evidence indicating that some antidepressant drugs promote dendritic outgrowth
      and increase synaptic protein levels through mTOR signalling; however, other
      antidepressant drugs seem to act via a different pathway. mTOR signalling may be
      a promising target for the development of new antidepressant drugs. 

PMID- 24901416
TI  - Gastrointestinal endogenous proteins as a source of bioactive peptides--an in
      silico study.
AB  - Dietary proteins are known to contain bioactive peptides that are released during
      digestion. Endogenous proteins secreted into the gastrointestinal tract represent
      a quantitatively greater supply of protein to the gut lumen than those of dietary
      origin. Many of these endogenous proteins are digested in the gastrointestinal
      tract but the possibility that these are also a source of bioactive peptides has
      not been considered. An in silico prediction method was used to test if bioactive
      peptides could be derived from the gastrointestinal digestion of gut endogenous
      proteins. Twenty six gut endogenous proteins and seven dietary proteins were
      evaluated. The peptides present after gastric and intestinal digestion were
      predicted based on the amino acid sequence of the proteins and the known
      specificities of the major gastrointestinal proteases. The predicted resultant
      peptides possessing amino acid sequences identical to those of known bioactive
      peptides were identified. After gastrointestinal digestion (based on the in
      silico simulation), the total number of bioactive peptides predicted to be
      released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins
      and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins.
      Within the intact proteins and after simulated gastrointestinal digestion,
      angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most
      frequently observed in both the dietary and endogenous proteins. Among the
      dietary proteins, after in silico simulated gastrointestinal digestion, myosin
      was found to have the highest number of ACE-inhibitory peptide sequences (49
      peptides), while for the gut endogenous proteins, mucin-5AC had the greatest
      number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins
      may be an important source of bioactive peptides in the gut particularly since
      gut endogenous proteins represent a quantitatively large and consistent source of
      protein. 

PMID- 24901417
TI  - Genotyping of French Bacillus anthracis strains based on 31-loci multi locus VNTR
      analysis: epidemiology, marker evaluation, and update of the internet genotype
      database.
AB  - BACKGROUND: Bacillus anthracis is known to have low genetic variability. In spite
      of this lack of diversity, multiple-locus variable-number tandem repeat (VNTR)
      analysis (MLVA) and single nucleotide polymorphisms (SNPs) including the
      canonical SNPs assay (canSNP) have proved to be highly effective to differentiate
      strains. Five different MLVA schemes based on a collection of 31 VNTR loci
      (MLVA8, MLVA15, MLVA20, MLVA25 and MLVA31) with increased resolving power have
      been described. RESULTS: MLVA31 was applied to characterize the French National
      Reference Laboratory collection. The total collection of 130 strains is resolved
      in 35 genotypes. The 119 veterinary and environmental strains collection in
      France were resolved into 26 genotypes belonging to three canSNP lineages and
      four MLVA clonal complexes (CCs) with particular geographical clustering. A
      subset of seven loci (MLVA7) is proposed to constitute a first line assay. The
      loci are compatible with moderate resolution equipment such as agarose gel
      electrophoresis and show a good congruence value with MLVA31. The associated MLVA
      and SNP data was imported together with published genotyping data by taking
      advantage of major enhancements to the MLVAbank software and web site.
      CONCLUSIONS: The present report provides a wide coverage of the genetic diversity
      of naturally occurring B. anthracis strains in France as can be revealed by MLVA.
      The data obtained suggests that once such coverage is achieved, it becomes
      possible to devise optimized first-line MLVA assays comprising a sufficiently low
      number of loci to be typed either in one multiplex PCR or on agarose gels. Such a
      selection of seven loci is proposed here, and future similar investigations in
      additional countries will indicate to which extend the same selection can be used
      worldwide as a common minimum set. It is hoped that this approach will contribute
      to an efficient and low-cost routine surveillance of important pathogens for
      biosecurity such as B. anthracis.

PMID- 24901420
TI  - [Complications from an intraocular glass fibre 33 years after trauma].

PMID- 24901418
TI  - Palaeosymbiosis revealed by genomic fossils of Wolbachia in a strongyloidean
      nematode.
AB  - Wolbachia are common endosymbionts of terrestrial arthropods, and are also found
      in nematodes: the animal-parasitic filaria, and the plant-parasite Radopholus
      similis. Lateral transfer of Wolbachia DNA to the host genome is common. We
      generated a draft genome sequence for the strongyloidean nematode parasite
      Dictyocaulus viviparus, the cattle lungworm. In the assembly, we identified
      nearly 1 Mb of sequence with similarity to Wolbachia. The fragments were unlikely
      to derive from a live Wolbachia infection: most were short, and the genes were
      disabled through inactivating mutations. Many fragments were co-assembled with
      definitively nematode-derived sequence. We found limited evidence of expression
      of the Wolbachia-derived genes. The D. viviparus Wolbachia genes were most
      similar to filarial strains and strains from the host-promiscuous clade F. We
      conclude that D. viviparus was infected by Wolbachia in the past, and that clade
      F-like symbionts may have been the source of filarial Wolbachia infections. 

PMID- 24901419
TI  - Trends in AIDS-defining opportunistic illnesses incidence over 25 years in Rio de
      Janeiro, Brazil.
AB  - OBJECTIVES: To assess the temporal trends in incidence of AIDS-defining
      opportunistic illnesses in an urban cohort of a middle-income country. METHODS:
      HIV infected patients aged >= 18 years at cohort entry were included in this
      analysis. We calculated incidence rates per 1000 persons-years of observation for
      the first opportunistic illness presented after cohort enrollment, from 1987 to
      2012. Trends for overall and specific opportunistic illnesses were tested and
      incidence rate ratios for the most recent calendar period were calculated as the
      ratio between the incidence rate observed in the most recent period of the study
      (2009-2012) and the incidence rate observed in first period of the study (1987
      1990). RESULTS: Overall, 3378 patients were included in this analysis; of which
      1119 (33%) patients presented an opportunistic illness during follow up.
      Incidence rates of all opportunistic illnesses decreased over time, and the
      overall opportunistic illness incidence rates fell from 295.4/1000 persons-years
      in 1987-1990 to 34.6/1000 persons-years in 2009-2012. Tuberculosis, esophageal
      candidiasis, cerebral toxoplasmosis and Pneumocystis jirovecii pneumonia were the
      most incident opportunistic illnesses in the cohort. Tuberculosis had the highest
      incidence rate in the study period. The peak in tuberculosis incidence occurred
      in 1991-1993 (80.8/1000 persons-years). Cerebral toxoplasmosis was the third most
      incident opportunistic illness in the study, with a peak of incidence of
      43.6/1000 persons-year in 1987-1990. CONCLUSIONS: All opportunistic illnesses
      incidence rates decreased over the years but they still occur in an unacceptable
      frequency. Tuberculosis co-infection among HIV-infected persists as an important
      challenge for health care professionals and policy makers in our setting.
      Impressively high rates of cerebral toxoplasmosis were found suggesting that its
      incidence among HIV-infected is linked to the high prevalence of Toxoplasma
      gondii infection in the general population.

PMID- 24901421
TI  - [Histopathological findings of DSAEK under failed penetrating keratoplasty].

PMID- 24901422
TI  - [Epithelial invasion after traumatic flap dislocation].

PMID- 24901423
TI  - [Subcutaneous dirofilariasis of the eyelid].

PMID- 24901424
TI  - [Central serous chorioretinitis and depressive disorder - a psychosomatic
      perspective].
AB  - Central serous chorioretinitis serosa is repeatedly brought into aetiological
      considerations with a rather unspecific concept of distress. Depressive disorder
      represents a specific stressor, which is known in cardiology or diabetology as a
      significant risk factor. In the present case report, the clinical correlation
      between a central serous chorioretinitis and a depressive disorder is shown from
      a psychosomatic point of view, comparing a sequentially-reactive understanding of
      the disorder complex with a preferable model of simultaneous entanglement. 

PMID- 24901425
TI  - [Choroidal thickness after scleral buckling surgery versus pars plana vitrectomy
      in macula-off rhegmatogenous retinal detachment].
AB  - PURPOSE: Enhanced depth imaging (EDI) optical coherence tomography (OCT) provides
      high-definition cross-sectional images of the choroid. Information on alterations
      in choroidal thickness (CT) after scleral buckling surgery (SBS) and pars plana
      vitretomy (PPV) are rare. METHODS: The medical charts of 44 patients (44 eyes)
      who underwent SBS versus PPV for macula-off rhegmatogenous retinal detachment
      (RRD) were retrospectively analysed. Patients with a follow-up >= 6 months were
      included. Postoperative EDI-OCT images concerning CT were evaluated 1 week, 1
      month and 6 months postoperatively in 2 groups: group 1: cerclage + cryopexy +
      subretinal fluid drainage (SRD) + SF6 or air (n = 28 eyes), group 2: PPV + laser
      photocoagulation + C3F8. Subfoveal CT was compared between the groups and with
      the non-operated fellow eye. RESULTS: Subfoveal CT in groups 1 and 2 was thicker
      1 week postoperatively. There were no significant differences between the groups
      2 or when comparing the operated eye with the fellow eye 1 and 6 months
      postoperatively. CONCLUSION: There were no differences in subfoveal CT 1 and 6
      months after SBS between the eye with macula-off RRD and the fellow eye. Thicker
      CT 1 week postoperatively after SBS may most likely be induced by scleral buckle
      reduced blood flow and increased haemostasis in the choroidal circulation and by
      scleral and choroidal inflammation after cryopexy versus laser photocoagulation
      after SBS versus PPV.

PMID- 24901426
TI  - [Outcome and complications after trabeculectomy depending on the preoperative
      intraocular pressure].
AB  - PURPOSE: Trabeculectomy is a frequently used surgical procedure in open-angle
      glaucomas. The present study analyses the outcome and complications after
      trabeculectomy or re-trabeculectomy depending on the preoperative intraocular
      pressure (IOP) < 30 mmHg and >= 30 mmHg. METHODS: One hundred and eighteen
      patients were included in this retrospective study. Primary ocular outcomes were
      the postoperative IOP at discharge and postoperative complications such as
      choroidal detachment and flattening of the anterior chamber. The necessity of
      postoperative interventions such as needle revisions, viscoelastic injections or
      surgical revision was documented. RESULTS: In this survey 118 patients (68 men,
      50 women) were included (age [arithmetic mean] 68.3 +/- 12.1 years). The
      postoperative follow-up period was 6-9 months. In 60 patients the preoperative
      IOP was < 30 mmHg, in 58 patients >= 30 mmHg. Postoperative complications were
      flattening of the anterior chamber (< 2 corneal thickness) in 11 patients (9.3 %)
      and temporary choroidal detachment in 20 patients (16.9 %). On the day of
      discharge the mean IOP was 9.8 mmHg. Hence the IOP was on average reduced by 17
      mmHg (SD 11.2 mmHg). Postoperative interventions were necessary in 28 patients
      (23.7 %). Seventeen (14.4 %) developed tenon cysts which were treated by needle
      revision of the bleb. Nine patients (7.6 %) underwent a viscoelastic injection
      for persistent hypotony and 10 patients underwent bleb revision (8.5 %).
      CONCLUSIONS: This study does not show statistically significant differences
      depending on preoperative IOP in temporary choroidal detachment and postoperative
      interventions. A postoperative flattening of the anterior chamber was found
      statistically significantly more often in patients with higher preoperative IOP.

PMID- 24901427
TI  - Electroconvulsive therapy for frontotemporal dementia with comorbid major
      depressive disorder.

PMID- 24901428
TI  - Electroconvulsive therapy in a patient with moyamoya syndrome.
AB  - We report on a 30-year-old woman diagnosed with moyamoya syndrome resulting from
      sickle cell disease who developed catatonia and was successfully treated with
      electroconvulsive therapy (ECT). Neuroimaging revealed severe tandem narrowing of
      the left internal carotid artery with diminished cerebral blood flow, moderate
      narrowing of the right supraclinoid aspect of the right internal carotid artery,
      and associated numerous lenticulostriate collaterals bilaterally, consistent with
      moyamoya. The patient presented with mutism; posturing; immobility; stupor;
      withdrawal; refusal to eat, drink, or speak; and staring, supporting a diagnosis
      of catatonia. It initially responded to a lorazepam challenge; however, a
      complicated hospital course and deterioration of the patient's condition,
      including septic shock, delirium, and continued catatonic symptoms, led to the
      pursuit of ECT to treat her symptoms. We discuss the risks involved with the
      administration of ECT in a patient with fragile cerebral vasculature and the
      successful treatment of catatonia in this patient without resultant stroke or
      cerebral hemorrhage. 

PMID- 24901429
TI  - Images in electroconvulsive therapy: ECS dose-dependently increases cell
      proliferation in the subgranular region of the rat hippocampus.
AB  - Stress and depression are associated with impaired neuroplasticity in the
      hippocampus; there is a decrease in neurogenesis, which is hypothesized to
      decrease the adaptative competence of the organism. Representative light
      microscopy images are presented which show that 6 once-daily electroconvulsive
      shocks (ECS), dose-dependently increased new cell formation in the subgranular
      region of the hippocampus in healthy adult male Wistar rats (10 sections per rat,
      3 rats in each of sham ECS, 10 mC, and 40 mC groups). These neuroplasticity
      changes, demonstrated 1 month after the last ECS, may explain a part of the
      mechanism of action of electroconvulsive therapy in conditions such as
      depression. 

PMID- 24901430
TI  - Images in electroconvulsive therapy: electroconvulsive shocks dose-dependently
      increase dendritic arborization in the CA1 region of the rat hippocampus.
AB  - Stress and depression are associated with impaired neuroplasticity in the
      hippocampus: there is decreased dendritic arborization and synaptogenesis, which
      is hypothesized to explain decreased adaptive competence of the organism.
      Representative light microscopy images are presented that show that 6 once-daily
      electroconvulsive shocks (ECSs) dose-dependently increased dendritic arborization
      in the CA1 region of the hippocampus in healthy, adult, male Wistar rats (n = 10
      in each of sham, 10-mC, and 40-mC ECS groups). These neuroplasticity changes,
      identified 1 month after the last ECS, may explain a part of the mechanism of
      action of electroconvulsive therapy in conditions such as depression. 

PMID- 24901431
TI  - Etomidate is associated with longer seizure duration, lower stimulus intensity,
      and lower number of failed trials in electroconvulsive therapy compared with
      thiopental.
AB  - OBJECTIVE: Induction agents used for electroconvulsive therapy (ECT) may alter
      seizure parameters. In this study, we aimed to investigate the effects of
      etomidate and thiopental on seizure-related variables. METHODS: Registries of
      patients who received ECT between 2010 and 2013 in a tertiary psychiatry clinic
      were evaluated retrospectively. The information of patients who were on the same
      induction agent and muscle relaxant during the whole treatment course was
      assessed. Primary outcome measures were total number of ECT sessions, mean
      peripheral and central seizure duration, cumulative stimulus intensity, and the
      number of adequate seizures per total number of stimuli. Secondary measures were
      maximum systolic-diastolic and mean blood pressure, peak heart rate, and the
      frequency of antihypertensive drug use during the sessions. RESULTS: Although the
      total number of ECT sessions is similar between the etomidate (n = 43) and
      thiopenthal (n = 31) groups, the mean seizure duration per stimuli was
      significantly longer whereas the cumulative stimulus intensity was lower in the
      etomidate group. The number of adequate seizures obtained in relation with the
      number of stimuli was also significantly higher, indicating increased probability
      of eliciting an adequate seizure with etomidate. During threshold determination,
      the number of stimuli needed to provide an adequate seizure was marginally less
      with etomidate. No group difference was observed in hemodynamic changes and the
      frequency of antihypertensive use. CONCLUSIONS: Etomidate use, compared with
      thiopental as an induction agent, is associated with longer seizure duration with
      less cumulative intensity. The use of etomidate reduces the number of failed
      trials and may prevent the application of unnecessary electrical stimuli with a
      possibly safe hemodynamic profile.

PMID- 24901432
TI  - Electroconvulsive therapy practice in Catalonia: a survey study comparing data
      from 1993 and 2010.
AB  - OBJECTIVE: The aim of this study was to assess the current use of
      electroconvulsive therapy (ECT) in Catalonia (Spain) as compared with ECT
      practice 17 years ago (1993). METHODS: This was a descriptive, cross-sectional
      study using a structured questionnaire to collect data regarding the use of ECT
      in Catalan psychiatric units in 2010. A comparative approach was used with
      respect to previously published data. RESULTS: Data were obtained from 25 of the
      27 units (92.6%) surveyed. The ECT was used in 20 facilities (80%, as opposed to
      60% in 1993), and in all cases, a brief-pulse device was used. The most commonly
      used anesthetic was propofol (65%), and most facilities recorded the seizure
      duration (95%). The ECT was always administered in combination with pharmacologic
      therapy, and the primary clinical indication was depression. Only 20% of the ECT
      procedures were performed in the inpatient unit. Written informed consent to
      administer ECT was obtained in all centers. CONCLUSIONS: The ECT practice in
      Catalonia has changed since the 1990s, being administered more often, in a more
      standardized way and across a larger number of psychiatric units. The results
      indicate considerable consensus with regard to its indications and conditions of
      application, which comply with current clinical practice guidelines and
      standards.

PMID- 24901433
TI  - Src kinases regulate de novo actin polymerization during exocytosis in
      neuroendocrine chromaffin cells.
AB  - The cortical actin network is dynamically rearranged during secretory processes.
      Nevertheless, it is unclear how de novo actin polymerization and the disruption
      of the preexisting actin network control transmitter release. Here we show that
      in bovine adrenal chromaffin cells, both formation of new actin filaments and
      disruption of the preexisting cortical actin network are induced by Ca2+
      concentrations that trigger exocytosis. These two processes appear to regulate
      different stages of exocytosis; whereas the inhibition of actin polymerization
      with the N-WASP inhibitor wiskostatin restricts fusion pore expansion, thus
      limiting the release of transmitters, the disruption of the cortical actin
      network with cytochalasin D increases the amount of transmitter released per
      event. Further, the Src kinase inhibitor PP2, and cSrc SH2 and SH3 domains also
      suppress Ca2+-dependent actin polymerization, and slow down fusion pore expansion
      without disturbing the cortical F-actin organization. Finally, the isolated SH3
      domain of c-Src prevents both the disruption of the actin network and the
      increase in the quantal release induced by cytochalasin D. These findings support
      a model where a rise in the cytosolic Ca2+ triggers actin polymerization through
      a mechanism that involves Src kinases. The newly formed actin filaments would
      speed up the expansion of the initial fusion pore, whereas the preexisting actin
      network might control a different step of the exocytosis process. 

PMID- 24901434
TI  - Heat-shock protein 90 promotes nuclear transport of herpes simplex virus 1 capsid
      protein by interacting with acetylated tubulin.
AB  - Although it is known that inhibitors of heat shock protein 90 (Hsp90) can inhibit
      herpes simplex virus type 1 (HSV-1) infection, the role of Hsp90 in HSV-1 entry
      and the antiviral mechanisms of Hsp90 inhibitors remain unclear. In this study,
      we found that Hsp90 inhibitors have potent antiviral activity against standard or
      drug-resistant HSV-1 strains and viral gene and protein synthesis are inhibited
      in an early phase. More detailed studies demonstrated that Hsp90 is upregulated
      by virus entry and it interacts with virus. Hsp90 knockdown by siRNA or treatment
      with Hsp90 inhibitors significantly inhibited the nuclear transport of viral
      capsid protein (ICP5) at the early stage of HSV-1 infection. In contrast,
      overexpression of Hsp90 restored the nuclear transport that was prevented by the
      Hsp90 inhibitors, suggesting that Hsp90 is required for nuclear transport of
      viral capsid protein. Furthermore, HSV-1 infection enhanced acetylation of alpha
      tubulin and Hsp90 interacted with the acetylated alpha-tubulin, which is
      suppressed by Hsp90 inhibition. These results demonstrate that Hsp90, by
      interacting with acetylated alpha-tubulin, plays a crucial role in viral capsid
      protein nuclear transport and may provide novel insight into the role of Hsp90 in
      HSV-1 infection and offer a promising strategy to overcome drug-resistance. 

PMID- 24901435
TI  - P wave area for quantitative electrocardiographic assessment of left atrial
      remodeling.
AB  - BACKGROUND: Left atrial (LA) dilation provides a substrate for mitral
      regurgitation (MR) and atrial arrhythmias. ECG can screen for LA dilation but
      standard approaches do not assess LA geometry as a continuum, as does non
      invasive imaging. This study tested ECG-quantified P wave area as an index of LA
      geometry. METHODS AND RESULTS: 342 patients with CAD underwent ECG and CMR within
      7 (0.1+/-1.4) days. LA area on CMR correlated best with P wave area in ECG lead
      V1 (r = 0.42, p<0.001), with lesser correlations for P wave amplitude and
      duration. P wave area increased stepwise in relation to CMR-evidenced MR severity
      (p<0.001), with similar results for MR on echocardiography (performed in 86% of
      patients). Pulmonary arterial (PA) pressure on echo was increased by 50% among
      patients in the highest (45+/-14 mmHg) vs. the lowest (31+/-9 mmHg) P wave area
      quartile of the population. In multivariate regression, CMR and echo-specific
      models demonstrated P wave area to be independently associated with LA size after
      controlling for MR, as well as echo-evidenced PA pressure. Clinical follow-up
      (mean 2.4+/-1.9 years) demonstrated ECG and CMR to yield similar results for
      stratification of arrhythmic risk, with a 2.6-fold increase in risk for atrial
      fibrillation/flutter among patients in the top P wave area quartile of the
      population (CI 1.1-5.9, p = 0.02), and a 3.2-fold increase among patients in the
      top LA area quartile (CI 1.4-7.0, p = 0.005). CONCLUSIONS: ECG-quantified P wave
      area provides an index of LA remodeling that parallels CMR-evidenced LA chamber
      geometry, and provides similar predictive value for stratification of atrial
      arrhythmic risk.

PMID- 24901436
TI  - Plasma Septin9 versus fecal immunochemical testing for colorectal cancer
      screening: a prospective multicenter study.
AB  - BACKGROUND: Screening improves outcomes related to colorectal cancer (CRC);
      however, suboptimal participation for available screening tests limits the full
      benefits of screening. Non-invasive screening using a blood based assay may
      potentially help reach the unscreened population. OBJECTIVE: To compare the
      performance of a new Septin9 DNA methylation based blood test with a fecal
      immunochemical test (FIT) for CRC screening. DESIGN: In this trial, fecal and
      blood samples were obtained from enrolled patients. To compare test sensitivity
      for CRC, patients with screening identified colorectal cancer (n = 102) were
      enrolled and provided samples prior to surgery. To compare test specificity
      patients were enrolled prospectively (n = 199) and provided samples prior to
      bowel preparation for screening colonoscopy. MEASUREMENTS: Plasma and fecal
      samples were analyzed using the Epi proColon and OC Fit-Check tests respectively.
      RESULTS: For all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9
      80.9%) and 68.0% (95% CI 58.2-76.5%) for Septin9 and FIT, respectively.
      Specificity of the Epi proColon test was 81.5% (95% CI 75.5-86.3%) compared with
      97.4% (95% CI 94.1-98.9%) for FIT. For paired samples, the sensitivity of the Epi
      proColon test (72.2% -95% CI 62.5-80.1%) was shown to be statistically non
      inferior to FIT (68.0%-95% CI 58.2-76.5%). When test results for Epi proColon and
      FIT were combined, CRC detection was 88.7% at a specificity of 78.8%.
      CONCLUSIONS: At a sensitivity of 72%, the Epi proColon test is non- inferior to
      FIT for CRC detection, although at a lower specificity. With negative predictive
      values of 99.8%, both methods are identical in confirming the absence of CRC.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01580540.

PMID- 24901437
TI  - Using HIV networks to inform real time prevention interventions.
AB  - OBJECTIVE: To reconstruct the local HIV-1 transmission network from 1996 to 2011
      and use network data to evaluate and guide efforts to interrupt transmission.
      DESIGN: HIV-1 pol sequence data were analyzed to infer the local transmission
      network. METHODS: We analyzed HIV-1 pol sequence data to infer a partial local
      transmission network among 478 recently HIV-1 infected persons and 170 of their
      sexual and social contacts in San Diego, California. A transmission network score
      (TNS) was developed to estimate the risk of HIV transmission from a newly
      diagnosed individual to a new partner and target prevention interventions.
      RESULTS: HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to
      sequences from at least one other participant (i.e., clustered). A high TNS (top
      25%) was significantly correlated with baseline risk behaviors (number of unique
      sexual partners and insertive unprotected anal intercourse (p = 0.014 and p =
      0.0455, respectively) and predicted risk of transmission (p<0.0001).
      Retrospective analysis of antiretroviral therapy (ART) use, and simulations of
      ART targeted to individuals with the highest TNS, showed significantly reduced
      network level HIV transmission (p<0.05). CONCLUSIONS: Sequence data from an HIV-1
      screening program focused on recently infected persons and their social and
      sexual contacts enabled the characterization of a highly connected transmission
      network. The network-based risk score (TNS) was highly correlated with
      transmission risk behaviors and outcomes, and can be used identify and target
      effective prevention interventions, like ART, to those at a greater risk for HIV
      1 transmission.

PMID- 24901439
TI  - Estimating the burden of paratyphoid a in Asia and Africa.
AB  - Despite the increasing availability of typhoid vaccine in many regions, global
      estimates of mortality attributable to enteric fever appear stable. While both
      Salmonella enterica serovar Typhi (S. Typhi) and serovar Paratyphi (S. Paratyphi)
      cause enteric fever, limited data exist estimating the burden of S. Paratyphi,
      particularly in Asia and Africa. We performed a systematic review of both English
      and Chinese-language databases to estimate the regional burden of paratyphoid
      within Africa and Asia. Distinct from previous reviews of the topic, we have
      presented two separate measures of burden; both incidence and proportion of
      enteric fever attributable to paratyphoid. Included articles reported laboratory
      confirmed Salmonella serovar classification, provided clear methods on sampling
      strategy, defined the age range of participants, and specified the time period of
      the study. A total of 64 full-text articles satisfied inclusion criteria and were
      included in the qualitative synthesis. Paratyphoid A was commonly identified as a
      cause of enteric fever throughout Asia. The highest incidence estimates in Asia
      came from China; four studies estimated incidence rates of over 150 cases/100,000
      person-years. Paratyphoid A burden estimates from Africa were extremely limited
      and with the exception of Nigeria, few population or hospital-based studies from
      Africa reported significant Paratyphoid A burden. While significant gaps exist in
      the existing population-level estimates of paratyphoid burden in Asia and Africa,
      available data suggest that paratyphoid A is a significant cause of enteric fever
      in Asia. The high variability in documented incidence and proportion estimates of
      paratyphoid suggest considerable geospatial variability in the burden of
      paratyphoid fever. Additional efforts to monitor enteric fever at the population
      level will be necessary in order to accurately quantify the public health threat
      posed by S. Paratyphi A, and to improve the prevention and treatment of enteric
      fever. 

PMID- 24901438
TI  - Rosa26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of
      homologous recombination in mammals in vivo.
AB  - Homologous recombination (HR) is critical for the repair of double strand breaks
      and broken replication forks. Although HR is mostly error free, inherent or
      environmental conditions that either suppress or induce HR cause genomic
      instability. Despite its importance in carcinogenesis, due to limitations in our
      ability to detect HR in vivo, little is known about HR in mammalian tissues.
      Here, we describe a mouse model in which a direct repeat HR substrate is targeted
      to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR
      GFP) mice, HR between two truncated EGFP expression cassettes can yield a
      fluorescent signal. In-house image analysis software provides a rapid method for
      quantifying recombination events within intact tissues, and the frequency of
      recombinant cells can be evaluated by flow cytometry. A comparison among 11
      tissues shows that the frequency of recombinant cells varies by more than two
      orders of magnitude among tissues, wherein HR in the brain is the lowest.
      Additionally, de novo recombination events accumulate with age in the colon,
      showing that this mouse model can be used to study the impact of chronic
      exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating
      agent similar to the cancer chemotherapeutic temozolomide, shows that the colon,
      liver and pancreas are susceptible to DNA damage-induced HR. Finally,
      histological analysis of the underlying cell types reveals that pancreatic acinar
      cells and liver hepatocytes undergo HR and also that HR can be specifically
      detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model
      provides new understanding of how tissue and age impact susceptibility to HR, and
      enables future studies of genetic, environmental and physiological factors that
      modulate HR in mammals. 

PMID- 24901440
TI  - Effect of lanthanide complex structure on cell viability and association.
AB  - A systematic study of the effect of hydrophobicity and charge on the cell
      viability and cell association of lanthanide metal complexes is presented. The
      terbium luminescent probes feature a macrocyclic polyaminocarboxylate ligand
      (DOTA) in which the hydrophobicity of the antenna and that of the carboxyamide
      pendant arms are independently varied. Three sensitizing antennas were
      investigated in terms of their function in vitro: 2-methoxyisophthalamide
      (IAM(OMe)), 2-hydroxyisophthalamide (IAM), and 6-methylphenanthridine (Phen). Of
      these complexes, Tb-DOTA-IAM exhibited the highest quantum yield, although the
      higher cell viability and more facile synthesis of the structurally related Tb
      DOTA-IAM(OMe) platform renders it more attractive. Further modification of this
      latter core structure with carboxyamide arms featuring hydrophobic benzyl, hexyl,
      and trifluoro groups as well as hydrophilic amino acid based moieties generated a
      family of complexes that exhibit high cell viability (ED50 > 300 MUM) regardless
      of the lipophilicity or the overall complex charge. Only the hexyl-substituted
      complex reduced cell viability to 60% in the presence of 100 MUM complex.
      Additionally, cellular association was investigated by ICP-MS and fluorescence
      microscopy. Surprisingly, the hydrophobic moieties did not increase cell
      association in comparison to the hydrophilic amino acid derivatives. It is thus
      postulated that the hydrophilic nature of the 2-methoxyisophthalamide antenna
      (IAM(OMe)) disfavors the cellular association of these complexes. As such,
      responsive luminescent probes based on this scaffold would be appropriate for the
      detection of extracellular species. 

PMID- 24901441
TI  - Pharmacokinetics of Naja sumatrana (equatorial spitting cobra) venom and its
      major toxins in experimentally envenomed rabbits.
AB  - BACKGROUND: The optimization of snakebite management and the use of antivenom
      depend greatly on the knowledge of the venom's composition as well as its
      pharmacokinetics. To date, however, pharmacokinetic reports on cobra venoms and
      their toxins are still relatively limited. In the present study, we investigated
      the pharmacokinetics of Naja sumatrana (Equatorial spitting cobra) venom and its
      major toxins (phospholipase A2, neurotoxin and cardiotoxin), following
      intravenous and intramuscular administration into rabbits. PRINCIPAL FINDINGS:
      The serum antigen concentration-time profile of the N. sumatrana venom and its
      major toxins injected intravenously fitted a two-compartment model of
      pharmacokinetics. The systemic clearance (91.3 ml/h), terminal phase half-life
      (13.6 h) and systemic bioavailability (41.9%) of N. sumatrana venom injected
      intramuscularly were similar to those of N. sputatrix venom determined in an
      earlier study. The venom neurotoxin and cardiotoxin reached their peak
      concentrations within 30 min following intramuscular injection, relatively faster
      than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively). Rapid
      absorption of the neurotoxin and cardiotoxin from the injection site into
      systemic circulation indicates fast onsets of action of these principal toxins
      that are responsible for the early systemic manifestation of envenoming. The more
      prominent role of the neurotoxin in N. sumatrana systemic envenoming is further
      supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5%)
      compared to that of the phospholipase A2 (Fi.m.=68.6%) or cardiotoxin
      (Fi.m.=45.6%). The incomplete absorption of the phospholipase A2 and cardiotoxin
      may infer the toxins' affinities for tissues at the injection site and their
      pathological roles in local tissue damages through synergistic interactions.
      CONCLUSION/SIGNIFICANCE: Our results suggest that the venom neurotoxin is
      absorbed very rapidly and has the highest bioavailability following intramuscular
      injection, supporting its role as the principal toxin in systemic envenoming.

PMID- 24901442
TI  - International telemedicine in pediatric cardiac critical care: a multicenter
      experience.
AB  - OBJECTIVE: To describe our multicenter experience in telemedicine-assisted
      pediatric cardiac critical care (PCCC) with four hospitals in Latin America from
      July 2011 to June 2013. MATERIALS AND METHODS: This was a descriptive study based
      on telemedicine encounters related to quality of communication, assessed
      information, activities, and recommendations. Comparison among centers was
      performed. A postimplementation survey was conducted through a 5-point Likert
      scale questionnaire investigating acceptance among professionals involved with
      the telemedicine service through the assessment of general satisfaction,
      perception about the work system, usefulness, and impact on medical practice.
      RESULTS: One thousand forty consultations were conducted for 476 patients.
      Postoperatively, patients were distributed into Risk Adjustment Classification
      for Congenital Heart Surgery (RACHS-1) categories as follows: 2%, 26%, 36%, 26%,
      and 10% in categories 1, 2, 3, 4, and 6, respectively. A real-time intervention
      took place in 23% of encounters. Of the 2,173 recommendations given, 70 were
      related to extracorporeal membrane oxygenation management. There was a different
      RACHS-1 distribution and encounter characteristics among centers. From a total of
      51 surveys sent, 27 responses were received, and among responders, overall
      satisfaction was very high (4.27 +/- 0.18), as well as work system quality (4.4
      +/- 0.37). Telemedicine was considered useful in the cardiac intensive care unit
      (3.86 +/- 0.60), for patient outcomes (3.8 +/- 0.51), and for education (3.7 +/-
      0.71). There was a difference in overall satisfaction, perception about
      telemedicine usefulness in education, and impact on medical practice among
      centers. CONCLUSIONS: An international, multicenter telemedicine program in PCCC
      is technologically and logistically feasible. Prospective interventions in our
      international multicenter telemedicine program should consider differences in
      staff composition, perception of needs, and patient population among centers.

PMID- 24901444
TI  - Improved marathon performance by in-race nutritional strategy intervention.
AB  - It was tested whether a marathon was completed faster by applying a
      scientifically based rather than a freely chosen nutritional strategy.
      Furthermore, gastrointestinal symptoms were evaluated. Nonelite runners performed
      a 10 km time trial 7 weeks before Copenhagen Marathon 2013 for estimation of
      running ability. Based on the time, runners were divided into two similar groups
      that eventually should perform the marathon by applying the two nutritional
      strategies. Matched pairs design was applied. Before the marathon, runners were
      paired based on their prerace running ability. Runners applying the freely chosen
      nutritional strategy (n = 14; 33.6 +/- 9.6 years; 1.83 +/- 0.09 m; 77.4 +/- 10.6
      kg; 45:40 +/- 4:32 min for 10 km) could freely choose their in-race intake.
      Runners applying the scientifically based nutritional strategy (n = 14; 41.9 +/-
      7.6 years; 1.79 +/- 0.11 m; 74.6 +/- 14.5 kg; 45:44 +/- 4:37 min) were targeting
      a combined in-race intake of energy gels and water, where the total intake
      amounted to approximately 0.750 L water, 60 g maltodextrin and glucose, 0.06 g
      sodium, and 0.09 g caffeine per hr. Gastrointestinal symptoms were assessed by a
      self-administered postrace questionnaire. Marathon time was 3:49:26 +/- 0:25:05
      and 3:38:31 +/- 0:24:54 hr for runners applying the freely chosen and the
      scientifically based strategy, respectively (p = .010, effect size=-0.43).
      Certain runners experienced diverse serious gastrointestinal symptoms, but
      overall, symptoms were low and not different between groups (p > .05). In
      conclusion, nonelite runners completed a marathon on average 10:55 min,
      corresponding to 4.7%, faster by applying a scientifically based rather than a
      freely chosen nutritional strategy. Furthermore, average values of
      gastrointestinal symptoms were low and not different between groups. 

PMID- 24901443
TI  - Influence of age, severity of infection, and co-infection on the duration of
      respiratory syncytial virus (RSV) shedding.
AB  - RSV is the most important viral cause of pneumonia and bronchiolitis in children
      worldwide and has been associated with significant disease burden. With the
      renewed interest in RSV vaccines, we provide realistic estimates on duration, and
      influencing factors on RSV shedding which are required to better understand the
      impact of vaccination on the virus transmission dynamics. The data arise from a
      prospective study of 47 households (493 individuals) in rural Kenya, followed
      through a 6-month period of an RSV seasonal outbreak. Deep nasopharyngeal swabs
      were collected twice each week from all household members, irrespective of
      symptoms, and tested for RSV by multiplex PCR. The RSV G gene was sequenced. A
      total of 205 RSV infection episodes were detected in 179 individuals from 40
      different households. The infection data were interval censored and assuming a
      random event time between observations, the average duration of virus shedding
      was 11.2 (95% confidence interval 10.1-12.3) days. The shedding durations were
      longer than previous estimates (3.9-7.4 days) based on immunofluorescence antigen
      detection or viral culture, and were shown to be strongly associated with age,
      severity of infection, and revealed potential interaction with other respiratory
      viruses. These findings are key to our understanding of the spread of this
      important virus and are relevant in the design of control programmes.

PMID- 24901445
TI  - Surface chemistry and entrapment of magnesium nanoparticles into polymeric
      micelles: a highly biocompatible tool for photothermal therapy.
AB  - A novel highly biocompatible nanosystem containing Mg nanoparticles is reported,
      characterized and tested as a suitable and non-toxic tool for photothermal
      therapy. 

PMID- 24901446
TI  - Influence of physiological sources on the impedance cardiogram analyzed using 4D
      FEM simulations.
AB  - Impedance cardiography is a simple and inexpensive method to acquire data on
      hemodynamic parameters. This study analyzes the influence of four dynamic
      physiological sources (aortic expansion, heart contraction, lung perfusion and
      erythrocyte orientation) on the impedance signal using a model of the human
      thorax with a high temporal resolution (125 Hz) based on human MRI data.
      Simulations of electromagnetic fields were conducted using the finite element
      method. The ICG signal caused by these sources shows very good agreement with the
      measured signals (r = 0.89). Standard algorithms can be used to extract
      characteristic points to calculate left ventricular ejection time and stroke
      volume (SV). In the presented model, the calculated SV equals the implemented
      left ventricular volume change of the heart. It is shown that impedance changes
      due to lung perfusion and heart contraction compensate themselves, and that
      erythrocyte orientation together with the aortic impedance basically form the ICG
      signal while taking its characteristic morphology from the aortic signal. The
      model is robust to conductivity changes of tissues and organ displacements. In
      addition, it reflects the multi-frequency behavior of the thoracic impedance. 

PMID- 24901447
TI  - Pregnancy in multiple sclerosis: a questionnaire study.
AB  - BACKGROUND: Multiple sclerosis (MS) preferentially affects females at
      childbearing age. For this reason patients and treating physicians were
      frequently confronted with questions concerning family planning, pregnancy and
      birth. OBJECTIVE: The aim of this study was to evaluate the expertise about
      pregnancy related topics in multiple sclerosis of neurologists in private
      practice. METHODS: We developed a survey with 16 multiple choice questions about
      pregnancy related topics and sent it to neurologists in private practice in
      Berlin, Germany. RESULTS: 56 completed questionnaires were sent back. 54% of all
      questions were answered correctly, 21% of the questions were answered with "I
      don't know". Correct answers were more often given by physicians who treat more
      than 400 MS patients per year (p = 0.001). Further positive associations were
      found for assumed relevance of the topic (p = 0.002) and the degree of counseling
      (p<0.001). CONCLUSION: To provide a comprehensive counseling, MS patients with
      desire for children should be counseled by physicians with a lot of experience in
      MS treatment.

PMID- 24901449
TI  - Sexual health communication within religious African-American families.
AB  - While research suggests youth prefer parents and family members to serve as the
      primary sources of sexual health information, fear and discomfort around
      discussing sex with their parents may leave youth misinformed and underinformed.
      This study explored sexual heath communication within religious African-American
      families. Thirty adolescents participated in four focus groups, and 19 adults and
      30 adolescents participated in six focus groups, at two predominantly African
      American Christian churches in Flint, MI. All data were analyzed inductively
      using a constant comparison approach. Nearly all participants reported attending
      church weekly. Three themes emerged and are described: initiating sex talks,
      using mistakes as teaching tools, and clarifying prevention messages.
      Participants highlighted the need for religious parents to offer both religious
      and practical guidance to adolescents about sexual health. Findings from this
      study may be used to inform future sexual health promotion interventions for
      religious African-American families. 

PMID- 24901448
TI  - Mosquitoes used to draw blood for arbovirus viremia determinations in small
      vertebrates.
AB  - Serial samples from the same individuals may be required for certain virological
      studies, however, some small animals cannot easily be blood-sampled. Therefore,
      we evaluated the use of Culex quinquefasciatus Say and Aedes albopictus Skuse
      mosquitoes as "biological syringes" to draw blood for virus titer determinations
      in small vertebrates. Groups of chicks (Gallus gallus), hamsters (Mesocricetus
      auratus), and house sparrows (Passer domesticus) were experimentally infected
      with West Nile virus (WNV) or Highlands J virus (HJV). In general, good
      correlation was seen between mosquito- and syringe-derived blood samples at
      titers >=5.0 log10 pfu/mL serum as compared with titers <5.0 log10 pfu/mL serum
      for chicks, hamsters, and sparrows. Ninety-two percent (24/26) of sparrows with
      virus titers >105 pfu/mL serum had mosquito- and syringe-derived titers within
      one log of each other. Sparrow viremia profiles generated from single mosquito
      blood meals and syringe were not significantly different (p>0.05). This technique
      is valuable for assessing the roles of small vertebrates in the ecologies of
      arboviruses, and could be used in applications beyond virology and infectious
      diseases, when <10 uL of whole blood is required. 

PMID- 24901450
TI  - Oxygen saturation profile in late-preterm and term infants: a prospective cohort
      study.
AB  - OBJECTIVE: To determine oxygen saturation profile over 6 h monitoring period in
      healthy late-preterm and term neonates during the first 48 h of age, and to
      assess the impact of gestational age, birth weight and method of delivery on this
      profile. STUDY DESIGN: Prospective cohort study of measurement of SpO2 over 6 h
      in 20 late-preterm (35 to 36 weeks gestation) and 40 term infants within 12 to 48
      h of birth was conducted. Infants with cardiorespiratory symptoms or need for
      cardiorespiratory support at birth were excluded. Percentage time spent at SpO2
      >90% and ?90% was calculated by gestational age and birth weight. RESULT: Late
      preterm infants and infants born weighing <2.5 kg spent approximately 7% of the
      time at SpO2 ?90%; this time decreased as gestational age and birth weight
      increased. Time at SpO2 >90% was significantly different between late-preterm and
      term infants (93% (5%) vs 96% (3%); P =0.002). Time at SpO2 >90% was not
      significantly different between males and females (95% (5%) vs 95% (4%), both
      n=30; P =0.72) or between vaginal births and cesarean births (95% (4%), n=32, vs
      95% (4%), n=28; P =0.39). Cumulative time with SpO2 <90 was mean (s.d.) of 25
      (18) in preterm vs 13 (10) min in term infants. CONCLUSION: Over a 6-h period
      healthy late-preterm and term infants spent significant time at SpO2 ?90%. Lower
      gestation and lower birth weight were associated with higher time at SpO2 ?90%.

PMID- 24901451
TI  - Antenatal magnesium sulfate and spontaneous intestinal perforation in infants
      less than 25 weeks gestation.
AB  - OBJECTIVE: Evaluate spontaneous intestinal perforation (SIP)/death among
      extremely low birthweight (ELBW) infants before, during and after initiation of
      an antenatal magnesium for neuroprotection protocol (MgPro). STUDY DESIGN: We
      tested associations between SIP/death and magnesium exposure, gestational age
      (GA) and interactions with GA and magnesium exposure in a cohort of inborn ELBW
      infants before, during and after MgPro. RESULT: One hundred and fifty-five ELBW
      infants were included, 81 before, 23 during and 51 after MgPro. ELBW infants
      (78.3%) were exposed to Mg during MgPro compared with 50.6% and 60.8% before and
      after, respectively. Incidence of SIP on protocol was 30.4% vs 12.9% off protocol
      (P=0.03). GA was strongly associated with SIP (P<0.01). Antenatal Mg dose was
      also associated with SIP/death regardless of epoch (odds ratio 9.3 (1.04-104.6)),
      but increased SIP/death was limited to those <25 weeks gestation. CONCLUSION:
      Higher Mg dose was associated with higher SIP and death risk among infants with
      the lowest birthweights. Validation of this observation in larger populations is
      warranted.

PMID- 24901453
TI  - Abdominal subcutaneous and visceral fat thickness in newborns: correlation with
      anthropometric and metabolic profile.
AB  - OBJECTIVE: To correlate abdominal subcutaneous and visceral fat thickness with
      anthropometric data and metabolic profile in newborns. STUDY DESIGN: A cross
      sectional study with 99 newborns was performed at Instituto de Medicina Integral
      Professor Fernando Figueira, Brazil. Abdominal subcutaneous and visceral
      thickness were measured by ultrasound. Glucose, insulin, homeostatic model
      assessment-insulin resistance (HOMA-IR), total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, very-low-density
      lipoprotein cholesterol and triglycerides were determined. Pearson correlation
      coefficients were calculated. RESULT: Abdominal subcutaneous fat thickness was
      positively correlated with birth weight (r=0.31; P<0.001), height (r=0.27;
      P<0.001) and abdominal circumference (r=0.26; P<0.001), but not with metabolic
      profile. Abdominal visceral fat thickness was correlated with abdominal
      circumference (r=0.23; P=0.01), insulin (r=0.21; P=0.04) and HOMA (r=0.24;
      P=0.02). The results remained the same among males and females. CONCLUSION:
      Abdominal fat distribution in newborns has a different correlation with
      anthropometric and metabolic profile. Abdominal subcutaneous fat thickness is
      positively correlated with anthropometric data whereas abdominal visceral fat
      thickness is correlated with insulin and HOMA-IR.

PMID- 24901454
TI  - A new basal hadrosauroid dinosaur (Dinosauria: Ornithopoda) with transitional
      features from the late cretaceous of Henan Province, China.
AB  - BACKGROUND: Southwestern Henan Province in central China contains many down
      faulted basins, including the Xixia Basin where the Upper Cretaceous continental
      sediments are well exposed. The Majiacun Formation is a major dinosaur-bearing
      stratigraphic unit that occurs in this basin. METHODOLOGY/PRINCIPAL FINDINGS: A
      new basal hadrosauroid dinosaur, Zhanghenglong yangchengensis gen. et sp. nov.,
      is named based on newly collected specimens from the middle Santonian Majiacun
      Formation of Zhoujiagou Village, Xixia Basin. Two transitional features between
      basal hadrosauroids and hadrosaurids are attached to the diagnosis of the new
      taxon, namely five maxillary foramina consisting of four small scattered ones
      anteroposteriorly arranged in a row and a large one adjacent to the articular
      facet for the jugal, and dentary tooth crowns bearing both median and distally
      offset primary ridges. Zhanghenglong also displays a unique combination of
      plesiomorphic and derived features of hadrosauroids, and is clearly
      morphologically transitional between basal hadrosauroids and hadrosaurids.
      Furthermore, some measurement attributes in osteology are applied to the
      quantitative analysis of Zhanghenglong. For these attributes, the partition of
      the dataset on most hadrosauroid species resulting from model-based cluster
      analysis almost matches taxonomic separation between basal hadrosauroids and
      hadrosaurids. Data of Zhanghenglong on selected measurement attributes straddle
      the two combinations of intervals of partitioned datasets respectively related to
      basal hadrosauroids and hadrosaurids. This condition is similar to mosaic
      evolution of morphological characters present in the specimens of the taxon. The
      phylogenetic analysis of Hadrosauroidea recovers a clade composed of
      Zhanghenglong, Nanyangosaurus, and Hadrosauridae with an unresolved polytomy.
      CONCLUSIONS/SIGNIFICANCE: Zhanghenglong is probably a relatively derived non
      hadrosaurid hadrosauroid, based on the inferences made from the morphological
      comparisons, quantitative evaluation of measurements, and cladistic analysis. In
      combination with information on the stratigraphy, phylogeny and biogeography, the
      material of Zhanghenglong provides direct evidence for the hypothesis that
      hadrosaurids might have originated in Asia.

PMID- 24901452
TI  - Inhaled nitric oxide usage in preterm infants in the NICHD Neonatal Research
      Network: inter-site variation and propensity evaluation.
AB  - OBJECTIVE: The use of inhaled nitric oxide (iNO) in preterm infants remains
      controversial. In October 2010, a National Institutes of Health consensus
      development conference cautioned against use of iNO in preterm infants. This
      study aims (1) to determine the prevalence and variability in use of iNO in the
      Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Neonatal Research Network (NICHD NRN) before and after the consensus conference
      and (2) separately, to examine associations between iNO use and severe
      bronchopulmonary dysplasia (BPD) or death. STUDY DESIGN: The NICHD NRN Generic
      Database collects data including iNO use on very preterm infants. A total of 13
      centers contributed data across the time period 2008 to 2011. Infants exposed or
      not to iNO were compared using logistic regression, which included factors
      related to risk as well as their likelihood of being exposed to iNO. RESULT: A
      total of 4885 infants were assessed between 2008 and 2011; 128 (2.6%) received
      iNO before day 7, 140 (2.9%) between day 7 and 28, and 47 (1.0%) at >28 days.
      Center-specific iNO use during 2008 to 2010 ranged from 21.9 to 0.4%; 12 of 13
      sites reduced usage and overall NRN iNO usage decreased from 4.6 to 1.6%
      (P<0.001) in 2011. The use of iNO started between day 7 and day 14 was more
      prevalent among younger infants with more severe courses in week 1 and associated
      with increased risk of severe BPD or death (odds ratio 2.24; 95% confidence
      interval 1.23 to 4.07). CONCLUSION: The variability and total use of iNO
      decreased in 2011 compared with 2008 to 2010. iNO administration started at ? day
      7 was associated with more severe outcomes compared with infants without iNO
      exposure.

PMID- 24901455
TI  - Revealing differences in metabolic flux distributions between a mutant strain and
      its parent strain Gluconacetobacter xylinus CGMCC 2955.
AB  - A better understanding of metabolic fluxes is important for manipulating
      microbial metabolism toward desired end products, or away from undesirable by
      products. A mutant strain, Gluconacetobacter xylinus AX2-16, was obtained by
      combined chemical mutation of the parent strain (G. xylinus CGMCC 2955) using DEC
      (diethyl sulfate) and LiCl. The highest bacterial cellulose production for this
      mutant was obtained at about 11.75 g/L, which was an increase of 62% compared
      with that by the parent strain. In contrast, gluconic acid (the main byproduct)
      concentration was only 5.71 g/L for mutant strain, which was 55.7% lower than
      that of parent strain. Metabolic flux analysis indicated that 40.1% of the carbon
      source was transformed to bacterial cellulose in mutant strain, compared with
      24.2% for parent strain. Only 32.7% and 4.0% of the carbon source were converted
      into gluconic acid and acetic acid in mutant strain, compared with 58.5% and 9.5%
      of that in parent strain. In addition, a higher flux of tricarboxylic acid (TCA)
      cycle was obtained in mutant strain (57.0%) compared with parent strain (17.0%).
      It was also indicated from the flux analysis that more ATP was produced in mutant
      strain from pentose phosphate pathway (PPP) and TCA cycle. The enzymatic activity
      of succinate dehydrogenase (SDH), which is one of the key enzymes in TCA cycle,
      was 1.65-fold higher in mutant strain than that in parent strain at the end of
      culture. It was further validated by the measurement of ATPase that 3.53-6.41
      fold higher enzymatic activity was obtained from mutant strain compared with
      parent strain. 

PMID- 24901457
TI  - SOX2+ cell population from normal human brain white matter is able to generate
      mature oligodendrocytes.
AB  - OBJECTIVES: A number of neurodegenerative diseases progress with a loss of
      myelin, which makes them candidate diseases for the development of cell
      replacement therapies based on mobilisation or isolation of the endogenous
      neural/glial progenitor cells, in vitro expansion, and further implantation.
      Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial
      progenitor cells in the subcortical white matter of the normal adult human brain,
      all of which demonstrate glial progenitor features. However, the heterogeneity
      and differentiation potential of this pool of cells is not yet well established.
      METHODS: We used diffusion tensor images, histopathology, and immunostaining
      analysis to demonstrate normal cytoarchitecture and the absence of abnormalities
      in human temporal lobe samples from patients with mesial temporal sclerosis.
      These samples were used to isolate and enrich glial progenitor cells in vitro,
      and later to detect such cells in vivo. RESULTS: We have identified a
      subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white
      matter of the normal adult human brain in vivo. These cells can be isolated and
      enriched in vitro, where they proliferate and generate immature (O4+) and mature
      (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+). CONCLUSION:
      Our results demonstrate the existence of a new glial progenitor cell
      subpopulation that expresses SOX2 in the white matter of the normal adult human
      brain. These cells might be of use for tissue regeneration procedures.

PMID- 24901458
TI  - Macrophage inflammatory protein-1alpha shows predictive value as a risk marker
      for subjects and sites vulnerable to bone loss in a longitudinal model of
      aggressive periodontitis.
AB  - Improved diagnostics remains a fundamental goal of biomedical research. This
      study was designed to assess cytokine biomarkers that could predict bone loss
      (BL) in localized aggressive periodontitis. 2,058 adolescents were screened. Two
      groups of 50 periodontally healthy adolescents were enrolled in the longitudinal
      study. One group had Aggregatibacter actinomycetemcomitans (Aa), the putative
      pathogen, while the matched cohort did not. Cytokine levels were assessed in
      saliva and gingival crevicular fluid (GCF). Participants were sampled, examined,
      and radiographed every 6 months for 2-3 years. Disease was defined as
      radiographic evidence of BL. Saliva and GCF was collected at each visit, frozen,
      and then tested retrospectively after detection of BL. Sixteen subjects with Aa
      developed BL. Saliva from Aa-positive and Aa-negative healthy subjects was
      compared to subjects who developed BL. GCF was collected from 16 subjects with BL
      and from another 38 subjects who remained healthy. GCF from BL sites in the 16
      subjects was compared to healthy sites in these same subjects and to healthy
      sites in subjects who remained healthy. Results showed that cytokines in saliva
      associated with acute inflammation were elevated in subjects who developed BL
      (i.e., MIP-1alpha MIP-1beta IL-alpha, IL-1beta and IL-8; p<0.01). MIP-1alpha was
      elevated 13-fold, 6 months prior to BL. When MIP-1alpha levels were set at 40
      pg/ml, 98% of healthy sites were below that level (Specificity); whereas, 93% of
      sites with BL were higher (Sensitivity), with comparable Predictive Values of
      98%; p<0.0001; 95% C.I. = 42.5-52.7). MIP-1alpha consistently showed elevated
      levels as a biomarker for BL in both saliva and GCF, 6 months prior to BL. MIP
      1alpha continues to demonstrate its strong candidacy as a diagnostic biomarker
      for both subject and site vulnerability to BL. 

PMID- 24901459
TI  - Effect of dispersion on surface interactions of cobalt(II) octaethylporphyrin
      monolayer on Au(111) and HOPG(0001) substrates: a comparative first principles
      study.
AB  - A density functional theory study of a cobalt(II) octaethylporphyrin (CoOEP)
      monolayer on Au(111) and HOPG(0001) surfaces was performed under periodic
      boundary conditions. Calculations with and without dispersion corrections are
      performed and the effect of van der Waals forces on the interface properties is
      analyzed. Calculations have determined that the CoOEP molecule tends to bind at
      the 3-fold and the 6-fold center sites on Au(111) and HOPG(0001), respectively.
      Geometric optimizations at the center binding sites have indicated that the
      porphyrin molecules (in the monolayer) lie flat on both substrates. Calculations
      also reveal that the CoOEP monolayer binds slightly more strongly to Au(111) than
      to HOPG(0001). Charge density difference plots disclose that charge is
      redistributed mostly around the porphyrin plane and the first layer of the
      substrates. Dispersion interactions cause a larger substrate to molecule charge
      pushback on Au(111) than on HOPG. CoOEP adsorption tends to lower the work
      functions of either substrate, qualitatively agreeing with the experimental
      photoelectron spectroscopic data. Comparison of the density of states (DOS) of
      the isolated CoOEP molecule with that on gold and HOPG substrates showed
      significant band shifts around the Fermi energy due to intermolecular orbital
      hybridization. Simulated STM images were plotted with the Tersoff-Hamann approach
      using the local density of states, which also agree with the experimental
      results. This study elucidates the role of dispersion for better describing
      porphyrin-substrate interactions. A DFT based overview of geometric, adsorption
      and electronic properties of a porphyrin monolayer on conductive surfaces is
      presented.

PMID- 24901456
TI  - Activation of focal adhesion kinase by Salmonella suppresses autophagy via an
      Akt/mTOR signaling pathway and promotes bacterial survival in macrophages.
AB  - Autophagy has emerged as an important antimicrobial host defense mechanism that
      not only orchestrates the systemic immune response, but also functions in a cell
      autonomous manner to directly eliminate invading pathogens. Pathogenic bacteria
      such as Salmonella have evolved adaptations to protect themselves from autophagic
      elimination. Here we show that signaling through the non-receptor tyrosine kinase
      focal adhesion kinase (FAK) is actively manipulated by the Salmonella SPI-2
      system in macrophages to promote intracellular survival. In wild-type
      macrophages, FAK is recruited to the surface of the Salmonella-containing vacuole
      (SCV), leading to amplified signaling through the Akt-mTOR axis and inhibition of
      the autophagic response. In FAK-deficient macrophages, Akt/mTOR signaling is
      attenuated and autophagic capture of intracellular bacteria is enhanced,
      resulting in reduced bacterial survival. We further demonstrate that enhanced
      autophagy in FAK(-/-) macrophages requires the activity of Atg5 and ULK1 in a
      process that is distinct from LC3-assisted phagocytosis (LAP). In vivo, selective
      knockout of FAK in macrophages resulted in more rapid clearance of bacteria from
      tissues after oral infection with S. typhimurium. Clearance was correlated with
      reduced infiltration of inflammatory cell types into infected tissues and reduced
      tissue damage. Together, these data demonstrate that FAK is specifically targeted
      by S. typhimurium as a novel means of suppressing autophagy in macrophages,
      thereby enhancing their intracellular survival.

PMID- 24901460
TI  - Silver nanoparticles increase cytotoxicity induced by intermediate frequency low
      voltages.
AB  - Electrical properties of the cells play a key role in biological processes.
      Intermediate frequencies of electrical fields influence the cells proliferation
      without heat generation and electrical stimulation. Silver nanoparticle (SNP) as
      a metallic agent can change the electrical characteristics of the cells. We study
      the effect of low voltages at an intermediate frequency (300 kHz) on a human
      breast adenocarcinoma cell line (MCF7) in the presence of SNPs. At first, cell
      toxicity of SNPs was determined at different concentrations. Then three different
      voltages were applied to the cells for 15 min, both in the presence and absence
      of SNPs. The treatments efficiency was evaluated by MTT assay. The results showed
      that the intermediate frequency-low voltages with SNPs not only provide an
      additive efficacy on cytotoxicity, but also a synergism was observed between
      these factors. By increasing the voltage from 3 to 9 V, a rising synergistic rate
      was observed. It seems that the synergistic effect between SNPs and the 300 kHz
      low voltages can inhibit cell proliferation and/or increases cell death of MCF-7,
      and hence increases treatment efficiency of SNPs, effectively. 

PMID- 24901461
TI  - Effects of microwave exposure and Gemcitabine treatment on apoptotic activity in
      Burkitt's lymphoma (Raji) cells.
AB  - We investigated the effects of 1.8 MHz Global System for Mobile Communications
      (GSM)-modulated microwave (MW) radiation on apoptotic level and cell viability of
      Burkitt's lymphoma (Raji) cells with or without Gemcitabine, which exhibits cell
      phase specificity, primarily killing cells undergoing DNA synthesis (S-phase).
      Raji cells were exposed to 1.8 GHz GSM-modulated MW radiation at a specific
      absorption rate (SAR) of 0.350 W/kg in a CO2 incubator. The duration of the
      exposure was 24 h. The amount of apoptotic cells was analyzed using Annexin V
      FITC and propidium iodide (PI) staining with flow cytometer. The apoptotic
      activity of MW exposed Raji cells was increased significantly. In addition, cell
      viability of exposed samples was significantly decreased. Combined exposure of MW
      and Gemcitabine increased the amount of apoptotic cells than MW radiation alone.
      Moreover, viability of MW + Gemcitabine exposed cells was lower than that of
      cells exposed only to MW. These results demonstrated that MW radiation exposure
      and Gemcitabine treatment have a synergistic effect on apoptotic activity of Raji
      cells. 

PMID- 24901462
TI  - Negatively-charged helices in the gas phase.
AB  - A polyalanine-based peptide which forms a stable, negatively-charged alpha-helix
      in the gas phase is reported. Addition of an N-terminal acidic residue forms a
      stabilizing hydrogen bond network and an electrostatic interaction with the
      helical dipole. Formation of this secondary structure was demonstrated using ion
      mobility-mass spectrometry and molecular modelling techniques. 

PMID- 24901464
TI  - Total daily pill burden in HIV-infected patients in the southern United States.
AB  - The need for antiretroviral therapy coupled with treatment of chronic co
      morbidities places HIV-infected patients at risk for polypharmacy. However, few
      studies have described overall pill burden among HIV-infected patients. HIV
      infected outpatients of the UNC Infectious Diseases Clinic were enrolled in this
      cross-sectional study. Subjects were contacted prior to a scheduled appointment
      and asked to bring all their medications to the visit. Daily total pill burden
      and medication type were recorded. 151 subjects were recruited: 76% male, 58%
      African American, 97% receiving antiretrovirals (ARVs). Median age was 48 (IRQ:
      42-54) years. The median number of medications per subject was 8 (IQR: 6-11), and
      the median individual daily pill burden was 8 pills (IQR: 5-15): 3 pills (range:
      2-5) for ARVs and 6 (range: 3-12.5) pills for non-ARVs. Duration of ART (per 2
      years increase) and more than 3 co-morbidities was significantly associated with
      high pill burden (over 10 pills per day) with adjusted OR of 2.09 (95% CI, 1.14
      3.84) and 8.04 (95% CI, 2.30-28.15), respectively. As patients with HIV age,
      strategies to reduce pill burden and number of medications will become
      increasingly critical to maintaining adherence, preventing medication errors, and
      serious drug-drug interactions.

PMID- 24901465
TI  - Cumulative effects of HIV illness and caring for children orphaned by AIDS on
      anxiety symptoms among adults caring for children in HIV-endemic South Africa.
AB  - Adults caring for children in HIV-endemic communities are at risk for poor
      psychological outcomes. However, we still have a limited understanding of how
      various HIV impacts--including caregiver's own HIV illness, responsibilities of
      caring for a child orphaned by AIDS, or both--affect psychological outcomes among
      caregivers. Furthermore, few studies have explored the relationship between
      stigma, HIV, and psychological outcomes among caregivers of children in HIV
      endemic communities. A cross-sectional survey conducted from 2009 to 2010
      assessed anxiety among 2477 caregivers of children in HIV-endemic South Africa.
      Chi-square tested differences in anxiety among caregivers living with HIV,
      caregivers of a child orphaned by AIDS, and caregivers affected with both
      conditions. Multivariate logistic regressions identified whether the relationship
      between HIV impacts and anxiety remained after controlling for socio-demographic
      co-factors. Mediation analysis tested the relationship between stigma, HIV, and
      anxiety. The odds of meeting threshold criteria for clinically relevant anxiety
      symptoms were two and a half times greater among caregivers living with HIV
      compared to nonaffected caregivers. The odds of meeting threshold criteria for
      clinically relevant anxiety symptoms were greatest among caregivers living with
      HIV and caring for a child orphaned by AIDS. Exposure to AIDS-related stigma
      partially mediated the relationship between HIV and anxiety. Interventions are
      needed to address caregiver psychological health, particularly among caregivers
      affected with both conditions of living with HIV and caring for a child orphaned
      by AIDS.

PMID- 24901468
TI  - ICU mortality should be the study endpoint for intensive care unit scoring
      systems.

PMID- 24901467
TI  - Antibody induction versus placebo, no induction, or another type of antibody
      induction for liver transplant recipients.
AB  - BACKGROUND: Liver transplantation is an established treatment option for end
      stage liver failure. To date, no consensus has been reached on the use of
      immunosuppressive T-cell antibody induction for preventing rejection after liver
      transplantation. OBJECTIVES: To assess the benefits and harms of
      immunosuppressive T-cell specific antibody induction compared with placebo, no
      induction, or another type of T-cell specific antibody induction for prevention
      of acute rejection in liver transplant recipients. SEARCH METHODS: We searched
      The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science
      Citation Index Expanded, and the World Health Organization (WHO) International
      Clinical Trials Registry Platform (ICTRP) until September 2013. SELECTION
      CRITERIA: Randomised clinical trials assessing immunosuppression with T-cell
      specific antibody induction compared with placebo, no induction, or another type
      of antibody induction in liver transplant recipients. Our inclusion criteria
      stated that participants within each included trial should have received the same
      maintenance immunosuppressive therapy. We planned to include trials with all of
      the different types of T-cell specific antibodies that are or have been used for
      induction (ie., polyclonal antibodies (rabbit of horse antithymocyte globulin
      (ATG), or antilymphocyte globulin (ALG)), monoclonal antibodies (muromonab-CD3,
      anti-CD2, or alemtuzumab), and interleukin-2 receptor antagonists (daclizumab,
      basiliximab, BT563, or Lo-Tact-1)). DATA COLLECTION AND ANALYSIS: We used RevMan
      analysis for statistical analysis of dichotomous data with risk ratio (RR) and of
      continuous data with mean difference (MD), both with 95% confidence intervals
      (CIs). We assessed the risk of systematic errors (bias) using bias risk domains
      with definitions. We used trial sequential analysis to control for random errors
      (play of chance). We presented outcome results in a summary of findings table.
      MAIN RESULTS: We included 19 randomised clinical trials with a total of 2067
      liver transplant recipients. All 19 trials were with high risk of bias. Of the 19
      trials, 16 trials were two-arm trials, and three trials were three-arm trials.
      Hence, we found 25 trial comparisons with antibody induction agents: interleukin
      2 receptor antagonist (IL-2 RA) versus no induction (10 trials with 1454
      participants); monoclonal antibody versus no induction (five trials with 398
      participants); polyclonal antibody versus no induction (three trials with 145
      participants); IL-2 RA versus monoclonal antibody (one trial with 87
      participants); and IL-2 RA versus polyclonal antibody (two trials with 112
      participants). Thus, we were able to compare T-cell specific antibody induction
      versus no induction (17 trials with a total of 1955 participants). Overall, no
      difference in mortality (RR 0.91; 95% CI 0.64 to 1.28; low-quality of evidence),
      graft loss including death (RR 0.92; 95% CI 0.71 to 1.19; low-quality of
      evidence), and adverse events ((RR 0.97; 95% CI 0.93 to 1.02; low-quality
      evidence) outcomes was observed between any kind of T-cell specific antibody
      induction compared with no induction when the T-cell specific antibody induction
      agents were analysed together or separately. Acute rejection seemed to be reduced
      when any kind of T-cell specific antibody induction was compared with no
      induction (RR 0.85, 95% CI 0.75 to 0.96; moderate-quality evidence), and when
      trial sequential analysis was applied, the trial sequential monitoring boundary
      for benefit was crossed before the required information size was obtained.
      Furthermore, serum creatinine was statistically significantly higher when T-cell
      specific antibody induction was compared with no induction (MD 3.77 MUmol/L, 95%
      CI 0.33 to 7.21; low-quality evidence), as well as when polyclonal T-cell
      specific antibody induction was compared with no induction, but this small
      difference was not clinically significant. We found no statistically significant
      differences for any of the remaining predefined outcomes - infection,
      cytomegalovirus infection, hepatitis C recurrence, malignancy, post-transplant
      lymphoproliferative disease, renal failure requiring dialysis, hyperlipidaemia,
      diabetes mellitus, and hypertension - when the T-cell specific antibody induction
      agents were analysed together or separately. Limited data were available for meta
      analysis on drug-specific adverse events such as haematological adverse events
      for antithymocyte globulin. No data were found on quality of life.When T-cell
      specific antibody induction agents were compared with another type of antibody
      induction, no statistically significant differences were found for mortality,
      graft loss, and acute rejection for the separate analyses. When interleukin-2
      receptor antagonists were compared with polyclonal T-cell specific antibody
      induction, drug-related adverse events were less common among participants
      treated with interleukin-2 receptor antagonists (RR 0.23, 95% CI 0.09 to 0.63;
      low-quality evidence), but this was caused by the results from one trial, and
      trial sequential analysis could not exclude random errors. We found no
      statistically significant differences for any of the remaining predefined
      outcomes: infection, cytomegalovirus infection, hepatitis C recurrence,
      malignancy, post-transplant lymphoproliferative disease, renal failure requiring
      dialysis, hyperlipidaemia, diabetes mellitus, and hypertension. No data were
      found on quality of life. AUTHORS' CONCLUSIONS: The effects of T-cell antibody
      induction remain uncertain because of the high risk of bias of the randomised
      clinical trials, the small number of randomised clinical trials reported, and the
      limited numbers of participants and outcomes in the trials. T-cell specific
      antibody induction seems to reduce acute rejection when compared with no
      induction. No other clear benefits or harms were associated with the use of any
      kind of T-cell specific antibody induction compared with no induction, or when
      compared with another type of T-cell specific antibody. Hence, more randomised
      clinical trials are needed to assess the benefits and harms of T-cell specific
      antibody induction compared with placebo, and compared with another type of
      antibody, for prevention of rejection in liver transplant recipients. Such trials
      ought to be conducted with low risks of systematic error (bias) and low risk of
      random error (play of chance).

PMID- 24901463
TI  - Comparison of adherence monitoring tools and correlation to virologic failure in
      a pediatric HIV clinical trial.
AB  - There is no consensus on a gold standard for monitoring adherence to
      antiretroviral therapy (ART). We compared different adherence monitoring tools in
      predicting virologic failure as part of a clinical trial. HIV-infected Thai and
      Cambodian children aged 1-12 years (N=207) were randomized to immediate-ART or
      deferred-ART until CD4% <15%. Virologic failure (VF) was defined as HIV-RNA >1000
      copies/mL after >=6 months of ART. Adherence monitoring tools were: (1) announced
      pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and
      (3) child self-report (self-reporting from children or caregivers to direct
      questioning by investigators during the clinic visit) of any missed doses in the
      last 3 days and in the period since the last visit. The Kappa statistic was used
      to describe agreement between each tool. The median age at ART initiation was 7
      years with median CD4% 17% and HIV-RNA 5.0 log(10)copies/mL and 92% received
      zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by
      announced pill count before VF in VF children was 92% compared to 98% in children
      without VF (p=0.03). Kappa statistics indicated slight to fair agreement between
      tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and
      caregiver education, significant predictors of VF were poor adherence by
      announced pill count (OR 4.56; 95%CI 1.78-11.69), reporting any barrier to
      adherence in the PACTG adherence questionnaire (OR 7.08; 95%CI 2.42-20.73), and
      reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR
      8.64; 95%CI 1.96-38.04). In conclusion, we recommend the child self-report of any
      missed doses since last visit for use in HIV research and in routine care
      settings, because it is easy and quick to administer and a strong association
      with development of VF.

PMID- 24901469
TI  - DUF581 is plant specific FCS-like zinc finger involved in protein-protein
      interaction.
AB  - Zinc fingers are a ubiquitous class of protein domain with considerable variation
      in structure and function. Zf-FCS is a highly diverged group of C2-C2 zinc finger
      which is present in animals, prokaryotes and viruses, but not in plants. In this
      study we identified that a plant specific domain of unknown function, DUF581 is a
      zf-FCS type zinc finger. Based on HMM-HMM comparison and signature motif
      similarity we named this domain as FCS-Like Zinc finger (FLZ) domain. A genome
      wide survey identified that FLZ domain containing genes are bryophytic in origin
      and this gene family is expanded in spermatophytes. Expression analysis of
      selected FLZ gene family members of A. thaliana identified an overlapping
      expression pattern suggesting a possible redundancy in their function. Unlike the
      zf-FCS domain, the FLZ domain found to be highly conserved in sequence and
      structure. Using a combination of bioinformatic and protein-protein interaction
      tools, we identified that FLZ domain is involved in protein-protein interaction. 

PMID- 24901473
TI  - Primary cutaneous versus salivary gland origin mucoepidermoid carcinoma.
AB  - Mucoepidermoid carcinoma (MEC) is a malignant glandular epithelial neoplasm that
      most commonly arises in the major salivary glands. Primary cutaneous MEC is very
      rare. There is a particular diagnostic challenge in determining the primary site
      of MEC when it is found in skin overlying the parotid gland. Attention to a
      combination of morphologic findings may be helpful. However, differentiation of
      primary cutaneous MEC from secondary cutaneous involvement by a parotid MEC may
      be unnecessary once the parotid gland is infiltrated. We report the case of a 54
      year-old male with a 2-cm asymptomatic mass overlying the right parotid gland,
      which was managed by excision of the affected skin, right total parotidectomy,
      and right neck dissection. Histopathologic and immunohistochemical findings were
      consistent with a cutaneous intermediate-grade MEC. Postoperative radiotherapy
      was deferred. The patient showed no evidence of recurrence or metastasis at 2
      months before self-discontinuing follow-up. To our knowledge, this is only the
      second reported case of MEC involving the parotid gland, but of overlying primary
      cutaneous origin.

PMID- 24901472
TI  - AprioriGWAS, a new pattern mining strategy for detecting genetic variants
      associated with disease through interaction effects.
AB  - Identifying gene-gene interaction is a hot topic in genome wide association
      studies. Two fundamental challenges are: (1) how to smartly identify combinations
      of variants that may be associated with the trait from astronomical number of all
      possible combinations; and (2) how to test epistatic interaction when all
      potential combinations are available. We developed AprioriGWAS, which brings two
      innovations. (1) Based on Apriori, a successful method in field of Frequent
      Itemset Mining (FIM) in which a pattern growth strategy is leveraged to
      effectively and accurately reduce search space, AprioriGWAS can efficiently
      identify genetically associated genotype patterns. (2) To test the hypotheses of
      epistasis, we adopt a new conditional permutation procedure to obtain reliable
      statistical inference of Pearson's chi-square test for the [Formula: see text]
      contingency table generated by associated variants. By applying AprioriGWAS to
      age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1
      (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO
      term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting
      genes. The epistatic interactions newly found by AprioriGWAS on AMD data are
      likely true interactions, since genes interacting with CFH are retinal genes, and
      GO term enrichment also verified that interaction between glycosaminoglycans
      (GAGs) and CFH plays an important role in disease pathology of AMD. By applying
      AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal
      effect show significant interactions. For example, multiple-SNP genotype patterns
      inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in
      many parts of the brain and are the most commonly found receptor in the nervous
      system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the
      central nervous system. GRIA1 and GABRB2 are relevant to mental disorders
      supported by multiple evidences. 

PMID- 24901474
TI  - Verrucous carcinoma of the foot diagnosed using p53 and Ki-67 immunostaining in a
      patient with diabetic neuropathy.

PMID- 24901470
TI  - Acute sterol o-acyltransferase 2 (SOAT2) knockdown rapidly mobilizes hepatic
      cholesterol for fecal excretion.
AB  - The primary risk factor for atherosclerotic cardiovascular disease is LDL
      cholesterol, which can be reduced by increasing cholesterol excretion from the
      body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a
      non-biliary pathway known as transintestinal cholesterol efflux (TICE). We
      previously showed that chronic knockdown of the hepatic cholesterol esterifying
      enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via
      TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed
      a high cholesterol diet to induce hepatic cholesterol accumulation and were then
      treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2.
      Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of
      cholesteryl ester in the liver was reduced by 70% without a reciprocal increase
      in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores
      resulted in a ~ 2-fold increase in fecal neutral sterol loss but no change in
      biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol
      carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our
      data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly
      mobilized and packaged onto nascent lipoproteins that feed cholesterol into the
      TICE pathway for fecal excretion.

PMID- 24901475
TI  - Loss of cytokeratin 20 and acquisition of thyroid transcription factor-1
      expression in a merkel cell carcinoma metastasis to the brain.
AB  - Merkel cell carcinoma (MCC) is recognized by its morphologic features and by its
      classic immunophenotypic properties. Although MCCs demonstrating nonclassic
      immunoreactivities have been described, a case documenting a change in
      immunophenotype during the course of disease progression has not been previously
      reported. We report a case of MCC that initially demonstrated cytokeratin 20
      positivity but lost expression in subsequent metastases. Likewise, thyroid
      transcription factor-1 was initially negative in the tumor but expression was
      present in metastatic lesions.

PMID- 24901476
TI  - Genetic background drives transcriptional variation in human induced pluripotent
      stem cells.
AB  - Human iPS cells have been generated using a diverse range of tissues from a
      variety of donors using different reprogramming vectors. However, these cell
      lines are heterogeneous, which presents a limitation for their use in disease
      modeling and personalized medicine. To explore the basis of this heterogeneity we
      generated 25 iPS cell lines under normalised conditions from the same set of
      somatic tissues across a number of donors. RNA-seq data sets from each cell line
      were compared to identify the majority contributors to transcriptional
      heterogeneity. We found that genetic differences between individual donors were
      the major cause of transcriptional variation between lines. In contrast, residual
      signatures from the somatic cell of origin, so called epigenetic memory,
      contributed relatively little to transcriptional variation. Thus, underlying
      genetic background variation is responsible for most heterogeneity between human
      iPS cell lines. We conclude that epigenetic effects in hIPSCs are minimal, and
      that hIPSCs are a stable, robust and powerful platform for large-scale studies of
      the function of genetic differences between individuals. Our data also suggest
      that future studies using hIPSCs as a model system should focus most effort on
      collection of large numbers of donors, rather than generating large numbers of
      lines from the same donor. 

PMID- 24901477
TI  - Crystal structure of the Neisseria gonorrhoeae MtrD inner membrane multidrug
      efflux pump.
AB  - Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of
      the sexually-transmitted disease gonorrhea. The control of this disease has been
      compromised by the increasing proportion of infections due to antibiotic
      resistant strains, which are growing at an alarming rate. The MtrCDE tripartite
      multidrug efflux pump, belonging to the hydrophobic and amphiphilic efflux
      resistance-nodulation-cell division (HAE-RND) family, spans both the inner and
      outer membranes of N. gonorrhoeae and confers resistance to a variety of
      antibiotics and toxic compounds. We here report the crystal structure of the
      inner membrane MtrD multidrug efflux pump, which reveals a novel structural
      feature that is not found in other RND efflux pumps. 

PMID- 24901478
TI  - Induction of cell-mediated immune responses in mice by DNA vaccines that express
      hepatitis C virus NS3 mutants lacking serine protease and NTPase/RNA helicase
      activities.
AB  - Effective therapeutic vaccines against virus infection must induce sufficient
      levels of cell-mediated immune responses against the target viral epitopes and
      also must avoid concomitant risk factors, such as potential carcinogenic
      properties. The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) carries
      a variety of CD4(+) and CD8(+) T cell epitopes, and induces strong HCV-specific T
      cell responses, which are correlated with viral clearance and resolution of acute
      HCV infection. On the other hand, NS3 possesses serine protease and nucleoside
      triphosphatase (NTPase)/RNA helicase activities, which not only play important
      roles in viral life cycle but also concomitantly interfere with host defense
      mechanisms by deregulating normal cellular functions. In this study, we
      constructed a series of DNA vaccines that express NS3 of HCV. To avoid the
      potential harm of NS3, we introduced mutations to the catalytic triad of the
      serine protease (H57A, D81A and S139A) and the NTPase/RNA helicase domain (K210N,
      F444A, R461Q and W501A) to eliminate the enzymatic activities. Immunization of
      BALB/c mice with each of the DNA vaccine candidates (pNS3[S139A/K210N],
      pNS3[S139A/F444A], pNS3[S139A/R461Q] and pNS3[S139A/W501A]) that expresses an NS3
      mutant lacking both serine protease and NTPase/helicase activities induced T cell
      immune responses to the degree comparable to that induced by the wild type NS3
      and the NS3/4A complex, as demonstrated by interferon-gamma production and
      cytotoxic T lymphocytes activities against NS3. The present study has
      demonstrated that plasmids expressing NS3 mutants, NS3(S139A/K210N),
      NS3(S139A/F444A), NS3(S139A/R461Q) and NS3(S139A/W501A), which lack both serine
      protease and NTPase/RNA helicase activities, would be good candidates for safe
      and efficient therapeutic DNA vaccines against HCV infection.

PMID- 24901480
TI  - Copper-catalyzed intramolecular trifluoromethylation of N-benzylacrylamides
      coupled with dearomatization: access to CF3-containing 2-azaspiro[4.5]decanes.
AB  - Copper-catalyzed intramolecular trifluoromethylation of N-benzylacrylamides
      coupled with dearomatization was achieved and used to regiospecifically construct
      a variety of trifluoromethylated 2-azaspiro[4.5]decanes bearing adjacent
      quaternary stereocenters under mild conditions in moderate to excellent yields. 

PMID- 24901479
TI  - Ethnic background and genetic variation in the evaluation of cancer risk: a
      systematic review.
AB  - The clinical use of genetic variation in the evaluation of cancer risk is
      expanding, and thus understanding how determinants of cancer susceptibility
      identified in one population can be applied to another is of growing importance.
      However there is considerable debate on the relevance of ethnic background in
      clinical genetics, reflecting both the significance and complexity of genetic
      heritage. We address this via a systematic review of reported associations with
      cancer risk for 82 markers in 68 studies across six different cancer types,
      comparing association results between ethnic groups and examining linkage
      disequilibrium between risk alleles and nearby genetic loci. We find that the
      relevance of ethnic background depends on the question. If asked whether the
      association of variants with disease risk is conserved across ethnic boundaries,
      we find that the answer is yes, the majority of markers show insignificant
      variability in association with cancer risk across ethnic groups. However if the
      question is whether a significant association between a variant and cancer risk
      is likely to reproduce, the answer is no, most markers do not validate in an
      ethnic group other than the discovery cohort's ancestry. This lack of
      reproducibility is not attributable to studies being inadequately populated due
      to low allele frequency in other ethnic groups. Instead, differences in local
      genomic structure between ethnic groups are associated with the strength of
      association with cancer risk and therefore confound interpretation of the implied
      physiologic association tracked by the disease allele. This suggest that a
      biological association for cancer risk alleles may be broadly consistent across
      ethnic boundaries, but reproduction of a clinical study in another ethnic group
      is uncommon, in part due to confounding genomic architecture. As clinical studies
      are increasingly performed globally this has important implications for how
      cancer risk stratifiers should be studied and employed. 

PMID- 24901482
TI  - Adaptation in constitutional dynamic libraries and networks, switching between
      orthogonal metalloselection and photoselection processes.
AB  - Constitutional dynamic libraries of hydrazones (a)A(b)B and acylhydrazones
      (a)A(c)C undergo reorganization and adaptation in response to a chemical effector
      (metal cations) or a physical stimulus (light). The set of hydrazones [(1)A(1)B,
      (1)A(2)B, (2)A(1)B, (2)A(2)B] undergoes metalloselection on addition of zinc
      cations which drive the amplification of Zn((1)A(2)B)2 by selection of the
      fittest component (1)A(2)B. The set of acylhydrazones [E-(1)A(1)C, (1)A(2)C,
      (2)A(1)C, (2)A(2)C] undergoes photoselection by irradiation of the system, which
      causes photoisomerization of E-(1)A(1)C into Z-(1)A(1)C with amplification of the
      latter. The set of acyl hydrazones [E-(1)A(1)C, (1)A(3)C, (2)A(1)C, (2)A(3)C]
      undergoes a dual adaptation via component exchange and selection in response to
      two orthogonal external agents: a chemical effector, metal cations, and a
      physical stimulus, light irradiation. Metalloselection takes place on addition of
      zinc cations which drive the amplification of Zn((1)A(3)C)2 by selection of the
      fittest constituent (1)A(3)C. Photoselection is obtained on irradiation of the
      acylhydrazones that leads to photoisomerization from E-(1)A(1)C to Z-(1)A(1)C
      configuration with amplification of the latter. These changes may be represented
      by square constitutional dynamic networks that display up-regulation of the pairs
      of agonists ((1)A(2)B, (2)A(1)B), (Z-(1)A(1)C, (2)A(2)C), ((1)A(3)C, (2)A(1)C),
      (Z-(1)A(1)C, (2)A(3)C) and the simultaneous down-regulation of the pairs of
      antagonists ((1)A(1)B, (2)A(2)B), ((1)A(2)C, (2)A(1)C), (E-(1)A(1)C, (2)A(3)C),
      ((1)A(3)C, (2)A(1)C). The orthogonal dual adaptation undergone by the set of
      acylhydrazones amounts to a network switching process. 

PMID- 24901481
TI  - Identifying the elusive sites of tyrosyl radicals in cytochrome c peroxidase:
      implications for oxidation of substrates bound at a site remote from the heme.
AB  - The location of the Trp radical and the catalytic function of the [Fe(IV)?O
      Trp191(*+)] intermediate in cytochrome c peroxidase (CcP) are well-established;
      however, the unambiguous identification of the site(s) for the formation of
      tyrosyl radical(s) and their possible biological roles remain elusive. We have
      now performed a systematic investigation of the location and reactivity of the
      Tyr radical(s) using multifrequency Electron Paramagnetic Resonance (EPR)
      spectroscopy combined with multiple-site Trp/Tyr mutations in CcP. Two tyrosines,
      Tyr71 and Tyr236, were identified as those contributing primarily to the EPR
      spectrum of the tyrosyl radical, recorded at 9 and 285 GHz. The EPR
      characterization also showed that the heme distal-side Trp51 is involved in the
      intramolecular electron transfer between Tyr71 and the heme and that formation of
      Tyr71(*) and Tyr236(*) is independent of the [Fe(IV)?O Trp191(*+)] intermediate.
      Tyr71 is located in an optimal position to mediate the oxidation of substrates
      binding at a site, more than 20 A from the heme, which has been reported recently
      in the crystal structures of CcP with bound guaicol and phenol [Murphy, E. J., et
      al. (2012) FEBS J. 279, 1632-1639]. The possibility of discriminating the radical
      intermediates by their EPR spectra allowed us to identify Tyr71(*) as the
      reactive species with the guaiacol substrate. Our assignment of the surface
      exposed Tyr236 as the other radical site agrees well with previous studies based
      on MNP labeling and protein cross-linking [Tsaprailis, G., and English, A. M.
      (2003) JBIC, J. Biol. Inorg. Chem. 8, 248-255] and on its covalent modification
      upon reaction of W191G CcP with 2-aminotriazole [Musah, R. A., and Goodin, D. B.
      (1997) Biochemistry 36, 11665-11674]. Accordingly, while Tyr71 acts as a true
      reactive intermediate for the oxidation of certain small substrates that bind at
      a site remote from the heme, the surface-exposed Tyr236 would be more likely
      related to oxidative stress signaling, as previously proposed. Our findings
      reinforce the view that CcP is the monofunctional peroxidase that most closely
      resembles its ancestor enzymes, the catalase-peroxidases, in terms of the higher
      complexity of the peroxidase reaction [Colin, J., et al. (2009) J. Am. Chem. Soc.
      131, 8557-8563]. The strategy used to identify the elusive Tyr radical sites in
      CcP may be applied to other heme enzymes containing a large number of Tyr and Trp
      residues and for which Tyr (or Trp) radicals have been proposed to be involved in
      their peroxidase or peroxidase-like reaction.

PMID- 24901483
TI  - Measurement of anterior scleral curvature using anterior segment OCT.
AB  - PURPOSE: To investigate and validate methods for measuring the radius of anterior
      scleral curvature using anterior segment optical coherence tomography images.
      METHODS: Twenty-four volunteers were enrolled in this study. Anterior segment
      optical coherence tomography images, centered on horizontal/vertical limbus,
      including adjacent anterior sclera, were obtained in addition to conventional
      images centered on the optical axis. Central horizontal, nasal, and temporal
      optical coherence tomography images were consolidated to a new image for
      subsequent analyses. The reference points of limbal surface and three scleral
      points were marked nasally and temporally. The radius of a best-fit circle to the
      six scleral points was derived (the BFC [best-fit circle] method) and the radii
      of two circles, the centers of which are on the optical axis and pass through the
      points of the scleral surface at 2 mm from the limbus nasally and temporally,
      were calculated (the axial method). To assess the reliability and accuracy of
      each method, intraobserver and interobserver agreements were analyzed and the
      radii of contact lenses with known curvatures were measured. RESULTS: The mean
      (+/-SD) radius of a BFC was 13.12 (+/-0.80) mm. The mean (+/-SD) radius of nasal
      anterior scleral curvature (13.33 +/- 1.12 mm) was significantly greater than
      that of temporal anterior scleral curvature (12.32 +/- 0.77 mm) (paired samples t
      test, p < 0.001). The BFC and axial methods showed excellent intraobserver and
      interobserver agreements for measurements (intraclass correlation coefficient >
      0.75, p < 0.001), whereas both methods showed a tendency to slightly
      underestimate the actual curvature of a rigid contact lens of known dimensions (
      0.07 +/- 0.13 mm [the BFC method] and -0.19 +/- 0.07 mm [the axial method],
      Wilcoxon signed rank test, p = 0.173 and p = 0.028, respectively). CONCLUSIONS:
      Anterior segment optical coherence tomography is a valuable tool for measuring
      the radii of anterior scleral curvatures by image processing and mathematical
      calculation and can provide useful information in specific clinical situations
      such as designing scleral lenses.

PMID- 24901484
TI  - Measurement of consensual accommodation in vision-impaired eyes.
AB  - PURPOSE: To measure the accommodative response in unsighted or profoundly vision
      impaired (PVI) eyes when accommodation is elicited in the fellow, sighted eye.
      METHODS: Eighty-eight unilaterally PVI subjects (UPS) and 97 bilaterally sighted
      subjects (BSS) (10 to 45 years) were enrolled. Subjects had clear ocular media
      for auto-refraction and could steadily fixate targets with the sighted eye. For
      BSS, a long-pass filter was placed in front of one eye to simulate unilateral
      blindness. Both eyes were measured with a Shin-Nippon auto-refractor while
      fixating a 4/40 letter at 4 m and then an N8 letter at 40 cm and at 33 cm.
      Accommodation was calculated as the difference between distance and near
      refraction. RESULTS: Only subjects with repeatable alignment between measurements
      were included in the analyses (64 UPS, 95 BSS). Results were analyzed using t
      test and a generalized linear mixed model including age, sightedness, distance
      spherical equivalent, and accommodation as factors. The t test found no
      significant difference between eyes for UPS (p = 0.981 at 40 cm and p = 0.663 at
      33 cm). For BSS, the sighting eye produced statistically significant but only
      slightly greater amounts of accommodation than the filtered eye (0.098 diopters
      [D], p = 0.002 at 40 cm and 0.189 D, p < 0.001 at 33 cm). The generalized linear
      mixed model found no difference between BSS and UPS in terms of difference in
      accommodation between eyes (p = 0.128 at 40 cm and p = 0.157 at 33 cm).
      CONCLUSIONS: The PVI eyes of unilaterally PVI individuals display similar
      accommodative response to their fellow, sighted eyes when accommodation is
      elicited by near target of up to 3 D to the fellow eye. However, the difference
      in accommodative response between PVI and fellow, sighted eye is related to the
      amount of accommodation elicited.

PMID- 24901485
TI  - Assessment of anterior segment parameters of keratoconus eyes in an Australian
      population.
AB  - PURPOSE: To assess anterior segment parameters of eyes with keratoconus (KC) at
      different clinical stages of disease. METHODS: KC and non-KC patients were
      recruited from public and private clinics in Melbourne, Australia. Axial length
      (AL), mean front corneal curvature (Front Km), mean back corneal curvature (Back
      Km), central corneal thickness (CCT), corneal thickness at the apex (CTA),
      corneal thickness at the thinnest point (CTT), anterior chamber depth (ACD), and
      corneal volume were noted for all the eyes. RESULTS: A total of 181 individuals
      comprising 44 (24.3%) subclinical KC, 118 (65.2%) clinical KC, and 19 (10.5%)
      control subjects were analyzed. Significant differences were noticed between the
      subclinical KC and control group for ACD and CTT, whereas between clinical and
      control groups, significant differences were obtained for AL, CCT, CTA, CTT, and
      ACD (p < 0.05). In the case of mild, moderate, and severe KC groups, Back Km,
      CCT, CTA, and CTT were significantly associated (p < 0.001) with increasing
      disease severity. We further did receiver operating characteristic analysis to
      confirm the importance of pachymetric parameters in differentiating between
      control and KC eyes. The area under the receiver operating characteristic curve
      value of CTT for subclinical and clinical KC was 0.68 and 0.82, which showed that
      it may be a potential marker for the early detection and prevention of KC.
      CONCLUSIONS: This study identified the anterior chamber parameters that differ
      between subclinical and clinical KC as well as the severity of KC. There is a
      significant reduction in CTT between control and subclinical eyes, although there
      are no significant alterations in Front and Back Km or AL between the two groups.
      Also, a progressive reduction in the pachymetric readings at the pupil center,
      apex, and thinnest corneal point was identified when comparing mild to severe KC
      groups. Thus, corneal thickness represents an important parameter that needs to
      be considered in monitoring KC disease severity.

PMID- 24901486
TI  - Repeatability of the modified Thorington card used to measure far heterophoria.
AB  - PURPOSE: To determine the interexaminer and intraexaminer repeatability of the
      modified Thorington test (TH) for distance vision in young adults and to compare
      these results with those observed for the heterophoria tests most commonly used
      in clinical practice. Agreement among tests was also assessed. METHODS: Distance
      heterophoria was quantified on two separate occasions by two examiners in 110
      subjects aged 18 to 32 years (mean, 19.74 years; SD, 2.5 years) using four
      different tests: cover test (CT) Von Graefe, Maddox rod, and modified TH. The
      repeatability of the tests and agreement between them was estimated by the Bland
      and Altman method whereby the mean difference and the 95% limits of agreement
      were determined as the coefficient of repeatability (COR) and coefficient of
      agreement. RESULTS: The Thorington test showed best interexaminer repeatability
      (COR = +/-1.43Delta), followed closely by CT (COR = +/-1.65Delta), whereas best
      intraexaminer repeatability was observed for CT (COR = +/-1.28Delta) followed by
      TH (COR = +/-1.51Delta). Among the different combinations of tests, TH and CT
      showed best agreement indicated by the lowest coefficient of agreement (+/
      2.23Delta) and a low mean difference (-0.63Delta) between measurements.
      CONCLUSIONS: Good interexaminer and intraexaminer repeatability was observed for
      both TH and CT, and agreement between the two tests was also good. Given the
      simple administration of the TH, we recommend its clinical use to quantify
      distance horizontal heterophoria.

PMID- 24901487
TI  - Utility values among myopic patients in mainland China.
AB  - PURPOSE: To elicit utility values of adult myopic patients in mainland China.
      METHODS: A valid sample of 442 myopia patients (spherical equivalent at least 
      0.5 diopters) aged 17 to 44 years who were scheduled to undergo refractive
      surgery were recruited. Information on time trade-off ([TTO] years of life
      willing to sacrifice for treatment of myopia) and standard gamble (SG) for
      blindness (risk of blindness from therapy, willing to sacrifice for treatment of
      myopia) utility values and sociodemographic and clinical data were obtained.
      RESULTS: The mean utility values based on TTO and SG were 0.96 +/- 0.05 (95%
      confidence interval [CI], 0.95 to 0.96; median, 0.98) and 0.93 +/- 0.09 (95% CI,
      0.92 to 0.94; median, 0.97), respectively. Myopic patients using contact lens had
      significantly higher TTO utility values than those wearing glasses (p < 0.001).
      There was no significant difference in the TTO and SG utility values by age, sex,
      occupation, educational levels, residence, reasons for refractive surgery, and
      severity and duration of myopia (p > 0.05). CONCLUSIONS: The TTO and SG produce
      similar mean utility values, but there is poor agreement between results for
      individuals from the two methods. Utility values associated with myopic patients
      obtained in this study or reported in the literature seem to be higher than those
      obtained for other ophthalmic conditions.

PMID- 24901489
TI  - Mathematical model for evaluating soft contact lens fit.
AB  - PURPOSE: To evaluate the effect of varying lens and ocular topography parameters
      on soft contact lens (SCL) fit, using a novel computer spreadsheet model.
      Although SCLs are worn by more than 100 million ametropes, the factors governing
      their fitting characteristics are poorly understood. METHODS: A spreadsheet-based
      computer model used a novel ellipto-conical corneal model coupled with population
      data on corneoscleral topography obtained in a previous clinical study. The model
      calculated lens edge strain (circumferential elongation) as a predictor of lens
      tightness. The following parameters were systematically varied: corneal
      curvature, corneal diameter, corneal shape factor, corneoscleral junction angle,
      lens base curve (BC), and diameter. RESULTS: The ellipto-conical corneal model
      showed closer concordance with actual measurements of corneal sagittal height
      than a simple elliptical model (limits of agreement, +/-0.20 vs. +/-0.25 mm; p =
      0.0015). For an eye with average ocular parameters wearing a typical SCL design
      (BC, 8.60; diameter, 14.2 mm), the model calculated an edge strain of 2.7%. For
      the same SCL, the tightest fit (8.5% strain) was found with the eye showing the
      combination of smallest, flattest, most aspheric cornea. Conversely, the loosest
      fitting (-2.6%) was found with the eye showing the combination of largest,
      steepest, least aspheric cornea. A change in BC of 0.4 mm typically resulted in
      changes in edge strain of less than 2.5%, whereas a change in diameter of 0.5 mm
      resulted in a change of less than 2%. Using the typical SCL design and average
      corneal model, wide variations in corneoscleral junction angle did not critically
      affect lens fit. More extreme combinations of SCL and ocular parameters resulted
      in edge strain likely to result in a tight (>6%) or loose fit (<0%). CONCLUSIONS:
      A novel ellipto-conical corneal model in conjunction with spreadsheet
      mathematical modeling proved to be a useful tool for attempting to understand the
      factors governing SCL fit.

PMID- 24901490
TI  - Threshold to predict astigmatism reduction after pterygium excision.
AB  - PURPOSE: To compare corneal astigmatism after pterygium excision, using limbal
      conjunctival autograft (LCA) with and without mitomycin C (MMC) and to establish
      a threshold for postoperative astigmatism reduction. METHODS: Sixty-eight eyes
      with primary pterygium were consecutively sampled and assigned to LCA with MMC
      (MMC+) or LCA without MMC (MMC-). Corneal lesion length, corneal lesion area,
      preoperative corneal astigmatism (PRCA), and postoperative corneal astigmatism
      (POCA) at 1, 3, and 6 months were assessed. RESULTS: Thirty-six men and 24 women
      (60 eyes), aged between 24 and 65 years (mean +/- SD, 41 +/- 8.2 years),
      completed the study. Thirty-one eyes were included in the MMC+ group and 29 were
      in the MMC- group. Both groups showed astigmatism reduction (p < 0.05; paired,
      two-tailed t test) 1 month after the surgery and remained stable. No differences
      were found between groups in corneal lesion length, corneal lesion area, or
      astigmatism results at the four time points (p > 0.05, independent t test).
      Preoperative corneal astigmatism showed a significant correlation with POCA at 6
      months (r = 0.529; p < 0.01). According to receiver operating characteristic
      curve analysis, the better threshold for astigmatism reduction with the surgery
      was 1.05 diopters of PRCA, with 82.5% sensitivity and 80.5% specificity.
      CONCLUSIONS: Both surgical procedures could have similar astigmatism results.
      Pterygium patients with more than 1.05 diopters of PRCA could reduce it after the
      surgery. Direct relationship between PRCA and POCA revealed that postoperative
      astigmatism reduction was partial. Therefore, for minimizing final astigmatism,
      preoperative values should be slightly above the threshold.

PMID- 24901488
TI  - Guinea pig ciliary muscle development.
AB  - PURPOSE: The purpose of this study was to develop a method for quantifying guinea
      pig ciliary muscle volume (CMV) and to determine its relationship to age and
      ocular biometric measurements. METHODS: Six albino guinea pigs' eyes were
      collected at each of five ages (n = 30 eyes). Retinoscopy and photography were
      used to document refractive error, eye size, and eye shape. Serial sections
      through the excised eyes were made and then labeled with an alpha-smooth muscle
      actin antibody. The ciliary muscle was then visualized with an Olympus BX51
      microscope, reconstructed with Stereo Investigator (MBF Bioscience), and analyzed
      using Neurolucida Explorer (MBF Bioscience). Full (using all sections) and
      partial (using a subset of sections) reconstruction methods were used to
      determine CMV. RESULTS: There was no significant difference between the full and
      partial volume determination methods (p = 0.86). The mean (+/-SD) CMV of the 1-,
      10-, 20-, 30-, and 90-day-old eyes was 0.40 (+/-0.16) mm, 0.48 (+/-0.13) mm, 0.67
      (+/-0.15) mm, 0.86 (+/-0.35) mm, and 1.09 (+/-0.63) mm, respectively. Ciliary
      muscle volume was significantly correlated with log age (p = 0.001), ocular
      length (p = 0.003), limbal circumference (p = 0.01), and equatorial diameter (p =
      0.003). It was not correlated with refractive error (p = 0.73) or eye shape (p =
      0.60). Multivariate regression determined that biometric variables were not
      significantly associated with CMV after adjustment for age. CONCLUSIONS: Three
      dimensional reconstruction was an effective means of determining CMV. These data
      provide evidence that ciliary muscle growth occurs with age in tandem with eye
      size in normal albino guinea pigs. Additional work is needed to determine the
      relationship between CMV and abnormal ocular growth.

PMID- 24901491
TI  - Design, synthesis, and biological evaluations of tumor-targeting dual-warhead
      conjugates for a taxoid-camptothecin combination chemotherapy.
AB  - Novel tumor-targeting dual-warhead conjugates, 2 (DW-1) and 3 (DW-2), which
      consist of a next-generation taxoid, 1 (SB-T-1214), and camptothecin as two
      warheads, self-immolative disulfide linkers for drug release, biotin as the tumor
      targeting moiety, and 1,3,5-triazine as the tripod splitter module, were designed
      and synthesized. The potency of 2 was evaluated against MX-1, MCF-7, ID8, L1210FR
      (BR+, biotin receptor overexpressed) and WI38 (BR-, normal) cell lines in the
      absence and presence of glutathione (GSH), which is an endogenous thiol that
      triggers drug release inside the cancer cells. With the GSH and resuspension
      protocol, 2 exhibited IC50 values of 3.22-9.80 nM against all BR+ cancer cell
      lines, and 705 nM against WI38. Thus, there was a two orders of magnitude higher
      selectivity to cancer cells. Also, a clear cooperative effect was observed for
      the taxoid-camptothecin combination when two drugs were delivered to the cancer
      cells specifically in the form of a dual-warhead conjugate.

PMID- 24901493
TI  - Construction of carbon-based two-dimensional crystalline nanostructure by
      chemical vapor deposition of benzene on Cu(111).
AB  - A new carbon-based two-dimensional crystalline nanostructure was discovered. The
      nanostructure was facilely constructed by chemical vapor deposition of benzene on
      Cu(111) in an ultrahigh vacuum chamber. A low temperature scanning tunneling
      microscopy and spectroscopy study of the nanostructure indicated that it has an
      orthorhombic superstructure and a semiconductor character with an energy gap of
      0.8 eV. An X-ray photoelectron spectroscopy study showed that C-C(sp(2)) bonding
      is predominantly preserved, suggesting a framework consisting of pi-conjugated
      building blocks. The periodic nanostructure was found to be a surprisingly
      excellent template for isolating and stabilizing magnetic atoms: Co atoms
      deposited on it can be well dispersed and form locally ordered atomic chains with
      their atomic magnetism preserved. Therefore the nanostructure may be suitable for
      organic spintronic applications. The most likely structural model for the
      nanostructure is proposed with the aid of density functional theory calculations
      and simulations, suggesting that the 2D nanostructure may consist of
      polyphenylene chains interconnected by Cu adatoms. 

PMID- 24901492
TI  - ChR2 mutants at L132 and T159 with improved operational light sensitivity for
      vision restoration.
AB  - The ectopic expression of microbial opsin-based optogenetic sensors, such as
      channelrhodopsin-2 (ChR2) in surviving inner retinal neurons, is a promising
      approach to restoring vision after retinal degeneration. However, a major
      limitation in using native ChR2 as a light sensor for vision restoration is the
      low light sensitivity of its expressing cells. Recently, two ChR2 mutations,
      T159C and L132C, were reported to produce higher photocurrents or have ultra
      light sensitivity. In this study, we created additional ChR2 mutants at these two
      sites to search for more light responsive ChR2 forms and evaluate their
      suitability for vision restoration by examining their light responsive properties
      in HEK cells and mouse retinal ganglion cells. We found additional ChR2 mutants
      at these two sites that showed a further increase in current amplitude at low
      light levels in the cells expressing these mutants, or operational light
      sensitivity. However, the increase in the operational light sensitivity was
      correlated with a decrease in temporal kinetics. Therefore, there is a trade-off
      between operational light sensitivity and temporal resolution for these more
      light responsive ChR2 mutants. Our results showed that for the two most light
      responsive mutants, L132C/T159C and L132C/T159S, the required light intensities
      for generating the threshold spiking activity in retinal ganglion cells were 1.5
      and nearly 2 log units lower than wild-type ChR2 (wt-ChR2), respectively.
      Additionally, their ChR2-mediated spiking activities could follow flicker
      frequencies up to 20 and 10 Hz, respectively, at light intensities up to 1.5 log
      units above their threshold levels. Thus, the use of these more light responsive
      ChR2 mutants could make the optogenetic approach to restoring vision more
      feasible. 

PMID- 24901494
TI  - Comparison of anti-Xa and activated partial thromboplastin time monitoring for
      heparin dosing in patients with cirrhosis.
AB  - BACKGROUND: Cirrhosis of the liver results in complex hemostatic changes that
      place patients at risk for both bleeding and thrombotic events. This study
      evaluates the adverse effects of anticoagulation with unfractionated heparin
      among patients with cirrhosis and analyzes the discrepancy between anti-Xa and
      activated partial thromboplastin time (aPTT) values for heparin monitoring among
      cirrhotics. METHODS: Patients with cirrhosis receiving unfractionated heparin
      were matched 2:1 to patients without evidence of cirrhosis anticoagulated with
      unfractioned heparin. Markers of bleeding events including blood product
      administration and use of heparin reversal were analyzed between groups. Patients
      from both groups with aPTT and anti-Xa values obtained at the same time were also
      analyzed. RESULTS: A higher incidence of blood product administration or use of
      heparin reversal was observed among patients with cirrhosis [35/105 (33.3%)
      versus 37/210 (17.6%), P = 0.002]. This finding was consistent among those
      receiving anticoagulation through an established anti-Xa-based heparin dosing
      protocol [23/62 (37.1%) versus 25/124 (20.2%), P = 0.013]. A decrease in
      hemoglobin greater than 2 g/dL or a platelet decrease 50% or greater from
      baseline was also more frequently identified among cirrhotics when receiving
      heparin therapy [20/105 (19%) versus 23/210 (11%), P = 0.049 and 21/105 (20%)
      versus 12/210 (6%), P < 0.001, respectively]. A total of 88 correlated anti-Xa
      and aPTT values from 35 patients with cirrhosis demonstrated supratherapeutic
      aPTT values for anti-Xa levels within the therapeutic range (P < 0.001). This
      discrepancy was not observed among controls. CONCLUSIONS: A greater use of blood
      products among the cirrhotic population may indicate potential bleeding events on
      therapy. A discrepancy in correlated anti-Xa and aPTT values among patients with
      cirrhosis may explain the propensity for adverse effects. Further study is
      required to identify effective heparin anticoagulation monitoring strategies in
      liver disease.

PMID- 24901495
TI  - Detection of codeine, morphine, 6-monoacetylmorphine, and meconin in human
      umbilical cord tissue: method validation and evidence of in utero heroin
      exposure.
AB  - BACKGROUND: Heroin abuse is a significant public health issue and is on the rise
      because of the unintended consequences of strengthening controls for nonmedical
      use of prescription pain killers. Included in this trend is an increase in opiate
      exposed newborns that are particularly vulnerable to a number of negative health
      outcomes. METHODS: After presenting a fully validated liquid chromatography
      tandem mass spectrometric method for codeine, morphine, 6-monoacetylmorphine, and
      meconin, a metabolite of the heroin contaminant noscapine, we compared the
      outcome of 46 authentic umbilical specimens with the results generated using a
      previous less sensitive method that did not include meconin. Additionally, we
      provided a summary of opiate finding from a year-long survey of specimens
      received into a commercial reference laboratory. RESULTS: The limits of detection
      for all 4 compounds were 0.1 ng/g, the limit of quantitation was 0.2 ng/g, and
      the assay was linear from 0.2 to 10.0 ng/g. Of the 46 comparative specimens, this
      method improved the identification of heroin exposure from 2 to 5, and the year
      long survey identified 86 heroin-exposed newborns with 11 of them identified by
      the sole identification of meconin. CONCLUSIONS: This study demonstrated that a
      more sensitive analytical platform and the inclusion of meconin in the opiates
      assay improved the ability to distinguish between in utero heroin exposure and
      maternal administration of codeine or morphine.

PMID- 24901496
TI  - DFT modeling of CO2 interaction with various aqueous amine structures.
AB  - In this study, the interaction of CO2 with aqueous monoethanolamine (MEA), 2
      amino-2-methyl-1-propanol (AMP), ethylenediamine (EDA), guanidine, and
      tetramethylguanidine (TMG) was studied by using density functional theory (DFT)
      modeling. MEA was chosen as the benchmark system, and the reaction pathways of
      carbamate as well as bicarbonate formations were analyzed thoroughly in order to
      evaluate the performances of the amines involved in this study in terms of
      thermodynamics and reaction kinetics. Among the materials considered, AMP was
      shown to be the most promising one due to its decreased product stability. 

PMID- 24901497
TI  - Evolution of amoxicillin resistance of Helicobacter pylori in vitro:
      characterization of resistance mechanisms.
AB  - Helicobacter pylori is the major cause of peptic ulcers and gastric cancer in
      humans. Treatment involves a two or three drug cocktail, typically including
      amoxicillin. Increasing levels of resistance to amoxicillin contribute to
      treatment failures, and higher levels of resistance are believed to be due to
      multiple genetic mutations. In this study, we examined the progression of
      spontaneous genetic mutations that contribute to amoxicillin resistance in H.
      pylori when exposed to increasing concentrations of amoxicillin in vitro. During
      the selection process, we isolated five strains each of which had progressively
      higher levels of resistance. Using a whole genome sequencing approach, we
      identified mutations in a number of genes, notably pbp1, pbp2, hefC, hopC, and
      hofH, and by sequencing these genes in each isolate we were able to map the order
      and gradual accumulation of mutations in these isolates. These five isolates,
      each expressing multiple mutated genes and four transformed strains expressing
      individually mutated pbp1, hefC, or hofH, were characterized using minimum
      inhibitory concentrations, amoxicillin uptake, and efflux studies. Our results
      indicate that mutations in pbp1, hefC, hopC, hofH, and possibly pbp2 contribute
      to H. pylori high-level amoxicillin resistance. The data also provide evidence
      for the complexity of the evolution of amoxicillin resistance in H. pylori and
      indicate that certain families of genes might be more susceptible to amoxicillin
      resistance mutations than others. 

PMID- 24901498
TI  - Pathways mediating the interaction between endothelial progenitor cells (EPCs)
      and platelets.
AB  - INTRODUCTION: Endothelial progenitor cells (EPCs) have an important role in the
      process of vascular injury repair. Platelets have been shown to mediate EPC
      recruitment, maturation and differentiation. Yet, the mechanism underlying this
      interaction is unclear. We, therefore, aimed to examine whether direct contact
      between platelets and EPCs is essential for the positive platelets-EPC effect,
      and to investigate the main mediators responsible for the improvement in EPCs
      function. METHODS: Human EPCs were isolated from donated buffy coats and cultured
      in either: 1. EPCs co-incubated with platelets placed in a 1 um-Boyden chamber.
      2. EPCs incubated with or without platelets in the presence or absence of
      bFGF/PDGF Receptor inhibitor (PDGFRI). After 7 days culture, EPCs ability to form
      colonies, proliferate and differentiate was examined. Culture supernatants were
      collected and growth factors levels were evaluated using ELISA. Growth factors
      mRNA levels in EPCs were evaluated using RT-PCR. RESULTS AND CONCLUSIONS: After 7
      days culture, EPCs functional properties were higher following co-incubation with
      platelets (directly or indirectly), implying that direct contact is not essential
      for the platelet's positive effect on EPCs. This effect was reduced by PDGFRI
      inhibition. Additionally, higher levels of PDGFB in EPCs-platelets supernatant
      and higher levels of PDGFC mRNA in EPCs co-incubated with platelets were found.
      In contrast, FGF and other potential mediators that were examined and inhibited
      did not significantly affect the interaction between platelets and EPCs. Thus, we
      conclude that PDGF has a central role in the interaction between platelets and
      EPCs. Further study is required to examine additional aspects of EPC-platelets
      interaction.

PMID- 24901499
TI  - Positive feedback of NDT80 expression ensures irreversible meiotic commitment in
      budding yeast.
AB  - In budding yeast, meiotic commitment is the irreversible continuation of the
      developmental path of meiosis. After reaching meiotic commitment, cells finish
      meiosis and gametogenesis, even in the absence of the meiosis-inducing signal. In
      contrast, if the meiosis-inducing signal is removed and the mitosis-inducing
      signal is provided prior to reaching meiotic commitment, cells exit meiosis and
      return to mitosis. Previous work has shown that cells commit to meiosis after
      prophase I but before entering the meiotic divisions. Since the Ndt80
      transcription factor induces expression of middle meiosis genes necessary for the
      meiotic divisions, we examined the role of the NDT80 transcriptional network in
      meiotic commitment. Using a microfluidic approach to analyze single cells, we
      found that cells commit to meiosis in prometaphase I, after the induction of the
      Ndt80-dependent genes. Our results showed that high-level expression of NDT80 is
      important for the timing and irreversibility of meiotic commitment. A modest
      reduction in NDT80 levels delayed meiotic commitment based on meiotic stages,
      although the timing of each meiotic stage was similar to that of wildtype cells.
      A further reduction of NDT80 resulted in the surprising finding of
      inappropriately uncommitted cells: withdrawal of the meiosis-inducing signal and
      addition of the mitosis-inducing signal to cells at stages beyond metaphase I
      caused return to mitosis, leading to multi-nucleate cells. Since Ndt80 enhances
      its own transcription through positive feedback, we tested whether positive
      feedback ensured the irreversibility of meiotic commitment. Ablating positive
      feedback in NDT80 expression resulted in a complete loss of meiotic commitment.
      These findings suggest that irreversibility of meiotic commitment is a
      consequence of the NDT80 transcriptional positive feedback loop, which provides
      the high-level of Ndt80 required for the developmental switch of meiotic
      commitment. These results also illustrate the importance of irreversible meiotic
      commitment for maintaining genome integrity by preventing formation of multi
      nucleate cells. 

PMID- 24901500
TI  - Plastic responses to elevated temperature in low and high elevation populations
      of three grassland species.
AB  - Local persistence of plant species in the face of climate change is largely
      mediated by genetic adaptation and phenotypic plasticity. In species with a wide
      altitudinal range, population responses to global warming are likely to differ at
      contrasting elevations. In controlled climate chambers, we investigated the
      responses of low and high elevation populations (1200 and 1800 m a.s.l.) of three
      nutrient-poor grassland species, Trifolium montanum, Ranunculus bulbosus, and
      Briza media, to ambient and elevated temperature. We measured growth-related,
      reproductive and phenological traits, evaluated differences in trait plasticity
      and examined whether trait values or plasticities were positively related to
      approximate fitness and thus under selection. Elevated temperature induced
      plastic responses in several growth-related traits of all three species. Although
      flowering phenology was advanced in T. montanum and R. bulbosus, number of
      flowers and reproductive allocation were not increased under elevated
      temperature. Plasticity differed between low and high elevation populations only
      in leaf traits of T. montanum and B. media. Some growth-related and phenological
      traits were under selection. Moreover, plasticities were not correlated with
      approximate fitness indicating selectively neutral plastic responses to elevated
      temperature. The observed plasticity in growth-related and phenological traits,
      albeit variable among species, suggests that plasticity is an important mechanism
      in mediating plant responses to elevated temperature. However, the capacity of
      species to respond to climate change through phenotypic plasticity is limited
      suggesting that the species additionally need evolutionary adaptation to adjust
      to climate change. The observed selection on several growth-related and
      phenological traits indicates that the study species have the potential for
      future evolution in the context of a warming climate. 

PMID- 24901501
TI  - Magnetite particles triggering a faster and more robust syntrophic pathway of
      methanogenic propionate degradation.
AB  - Interspecies electron transfer mechanisms between Bacteria and Archaea play a
      pivotal role during methanogenic degradation of organic matter in natural and
      engineered anaerobic ecosystems. Growing evidence suggests that in syntrophic
      communities electron transfer does not rely exclusively on the exchange of
      diffusible molecules and energy carriers such as hydrogen or formate, rather
      microorganisms have the capability to exchange metabolic electrons in a more
      direct manner. Here, we show that supplementation of micrometer-size magnetite
      (Fe3O4) particles to a methanogenic sludge enhanced (up to 33%) the methane
      production rate from propionate, a key intermediate in the anaerobic digestion of
      organic matter and a model substrate to study energy-limited syntrophic
      communities. The stimulatory effect most probably resulted from the establishment
      of a direct interspecies electron transfer (DIET), based on magnetite particles
      serving as electron conduits between propionate-oxidizing acetogens and carbon
      dioxide-reducing methanogens. Theoretical calculations revealed that DIET allows
      electrons to be transferred among syntrophic partners at rates which are
      substantially higher than those attainable via interspecies H2 transfer. Besides
      the remarkable potential for improving anaerobic digestion, which is a proven
      biological strategy for renewable energy production, the herein described
      conduction-based DIET could also have a role in natural methane emissions from
      magnetite-rich soils and sediments. 

PMID- 24901503
TI  - Professional organizations' role in supporting physicians to improve value in
      health care.

PMID- 24901504
TI  - Mechanism of action of agomelatine: a novel antidepressant exploiting synergy
      between monoaminergic and melatonergic properties.
AB  - ISSUE: A striking and unexpected pharmacologic synergy has been shown between
      antagonist actions at serotonergic 5HT2C receptors, and agonist actions at
      melatonergic receptors by agomelatine, a drug that has both of these properties.

PMID- 24901505
TI  - Paying attention to biased attention in drug addiction.

PMID- 24901506
TI  - Biological activity and molecular docking studies of curcumin-related alpha,beta
      unsaturated carbonyl-based synthetic compounds as anticancer agents and mushroom
      tyrosinase inhibitors.
AB  - Hyperpigmentation in human skin and enzymatic browning in fruits, which are
      caused by tyrosinase enzyme, are not desirable. Investigations in the discovery
      of tyrosinase enzyme inhibitors and search for improved cytotoxic agents continue
      to be an important line in drug discovery and development. In present work, a new
      series of 30 compounds bearing alpha,beta-unsaturated carbonyl moiety was
      designed and synthesized following curcumin as model. All compounds were
      evaluated for their effects on human cancer cell lines and mushroom tyrosinase
      enzyme. Moreover, the structure-activity relationships of these compounds are
      also explained. Molecular modeling studies of these new compounds were carried
      out to explore interactions with tyrosinase enzyme. Synthetic curcumin-like
      compounds (2a-b) were identified as potent anticancer agents with 81-82%
      cytotoxicity. Five of these newly synthesized compounds (1a, 8a-b, 10a-b) emerged
      to be the potent inhibitors of mushroom tyrosinase, providing further insight
      into designing compounds useful in fields of food, health, and agriculture. 

PMID- 24901507
TI  - A PCR based protocol for detecting indel mutations induced by TALENs and
      CRISPR/Cas9 in zebrafish.
AB  - Genome editing techniques such as the zinc-finger nucleases (ZFNs), transcription
      activator-like effecter nucleases (TALENs) and clustered regularly interspaced
      short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system Cas9 can induce
      efficient DNA double strand breaks (DSBs) at the target genomic sequence and
      result in indel mutations by the error-prone non-homologous end joining (NHEJ)
      DNA repair system. Several methods including sequence specific endonuclease
      assay, T7E1 assay and high resolution melting curve assay (HRM) etc have been
      developed to detect the efficiency of the induced mutations. However, these
      assays have some limitations in that they either require specific sequences in
      the target sites or are unable to generate sequencing-ready mutant DNA fragments
      or unable to distinguish induced mutations from natural nucleotide polymorphism.
      Here, we developed a simple PCR-based protocol for detecting indel mutations
      induced by TALEN and Cas9 in zebrafish. We designed 2 pairs of primers for each
      target locus, with one putative amplicon extending beyond the putative indel site
      and the other overlapping it. With these primers, we performed a qPCR assay to
      efficiently detect the frequencies of newly induced mutations, which was
      accompanied with a T-vector-based colony analysis to generate single-copy mutant
      fragment clones for subsequent DNA sequencing. Thus, our work has provided a very
      simple, efficient and fast assay for detecting induced mutations, which we
      anticipate will be widely used in the area of genome editing. 

PMID- 24901508
TI  - Understanding molecular crystals with dispersion-inclusive density functional
      theory: pairwise corrections and beyond.
AB  - CONSPECTUS: Molecular crystals are ubiquitous in many areas of science and
      engineering, including biology and medicine. Until recently, our ability to
      understand and predict their structure and properties using density functional
      theory was severely limited by the lack of approximate exchange-correlation
      functionals able to achieve sufficient accuracy. Here we show that there are many
      cases where the simple, minimally empirical pairwise correction scheme of
      Tkatchenko and Scheffler provides a useful prediction of the structure and
      properties of molecular crystals. After a brief introduction of the approach, we
      demonstrate its strength through some examples taken from our recent work. First,
      we show the accuracy of the approach using benchmark data sets of molecular
      complexes. Then we show its efficacy for structural determination using the
      hemozoin crystal, a challenging system possessing a wide range of strong and weak
      binding scenarios. Next, we show that it is equally useful for response
      properties by considering the elastic constants exhibited by the supramolecular
      diphenylalanine peptide solid and the infrared signature of water libration
      movements in brushite. Throughout, we emphasize lessons learned not only for the
      methodology but also for the chemistry and physics of the crystals in question.
      We further show that in many other scenarios where the simple pairwise correction
      scheme is not sufficiently accurate, one can go beyond it by employing a
      computationally inexpensive many-body dispersive approach that results in useful,
      quantitative accuracy, even in the presence of significant screening and/or
      multibody contributions to the dispersive energy. We explain the principles of
      the many-body approach and demonstrate its accuracy for benchmark data sets of
      small and large molecular complexes and molecular solids.

PMID- 24901502
TI  - Matricellular proteins in the trabecular meshwork: review and update.
AB  - Abstract Primary open-angle glaucoma (POAG) is a leading cause of blindness
      worldwide, and intraocular pressure (IOP) is an important modifiable risk factor.
      IOP is a function of aqueous humor production and aqueous humor outflow, and it
      is thought that prolonged IOP elevation leads to optic nerve damage over time.
      Within the trabecular meshwork (TM), the eye's primary drainage system for
      aqueous humor, matricellular proteins generally allow cells to modulate their
      attachments with and alter the characteristics of their surrounding extracellular
      matrix (ECM). It is now well established that ECM turnover in the TM affects
      outflow facility, and matricellular proteins are emerging as significant players
      in IOP regulation. The formalized study of matricellular proteins in TM has
      gained increased attention. Secreted protein acidic and rich in cysteine (SPARC),
      myocilin, connective tissue growth factor (CTGF), and thrombospondin-1 and -2
      (TSP-1 and -2) have been localized to the TM, and a growing body of evidence
      suggests that these matricellular proteins play an important role in IOP
      regulation and possibly the pathophysiology of POAG. As evidence continues to
      emerge, these proteins are now seen as potential therapeutic targets. Further
      study is warranted to assess their utility in treating glaucoma in humans. 

PMID- 24901511
TI  - The earliest giant Osprioneides borings from the Sandbian (late ordovician) of
      Estonia.
AB  - The earliest Osprioneides kampto borings were found in bryozoan colonies of
      Sandbian age from northern Estonia (Baltica). The Ordovician was a time of great
      increase in the quantities of hard substrate removed by single trace makers.
      Increased predation pressure was most likely the driving force behind the
      infaunalization of larger invertebrates such as the Osprioneides trace makers in
      the Ordovician. It is possible that the Osprioneides borer originated in Baltica
      or in other paleocontinents outside of North America. 

PMID- 24901510
TI  - Structure-function relationship of SW-AT-1, a serpin-type protease inhibitor in
      silkworm.
AB  - Although SW-AT-1, a serpin-type trypsin inhibitor from silkworm (Bombyx mori),
      was identified in previous study, its structure-function relationship has not
      been studied. In this study, SW-AT-1 was cloned from the body wall of silkworm
      and expressed in E. coli. rSW-AT-1 inhibited both trypsin and chymotrypsin in a
      concentration-dependent manner. The association rate constant for rSW-AT-1 and
      trypsin is 1.31*10-5 M-1s-1, for rSW-AT-1 and chymotrpsin is 2.85*10-6 M-1s-1.
      Circular dichroism (CD) assay showed 33% alpha-helices, 16% beta-sheets, 17%
      turns, and 31% random coils in the secondary structure of the protein. Enzymatic
      and CD analysis indicated that rSW-AT-1 was stable at wide pH range between 4-10,
      and exhibited the highest activity at weakly acidic or alkaline condition. The
      predicted three-dimensional structure of SW-AT-1 by PyMOL (v1.4) revealed a
      deductive reactive centre loop (RCL) near the C-terminus, which was extended from
      the body of the molecule. In addition to trypsin cleavage site in RCL, matrix
      assisted laser desorption ionization time of flight mass spectrometry indicated
      that the chymotrypsin cleavage site of SW-AT-1 was between F336 and T337 in RCL.
      Directed mutagenesis indicated that both the N- and C-terminal sides of RCL have
      effects on the activity, and G327 and E329 played an important role in the proper
      folding of RCL. The physiological role of SW-AT-1 in the defense responses of
      silkworm were also discussed. 

PMID- 24901512
TI  - Image of the month-quiz case.

PMID- 24901513
TI  - Image of the month-quiz case.

PMID- 24901509
TI  - Integrated pathway-based approach identifies association between genomic regions
      at CTCF and CACNB2 and schizophrenia.
AB  - In the present study, an integrated hierarchical approach was applied to: (1)
      identify pathways associated with susceptibility to schizophrenia; (2) detect
      genes that may be potentially affected in these pathways since they contain an
      associated polymorphism; and (3) annotate the functional consequences of such
      single-nucleotide polymorphisms (SNPs) in the affected genes or their regulatory
      regions. The Global Test was applied to detect schizophrenia-associated pathways
      using discovery and replication datasets comprising 5,040 and 5,082 individuals
      of European ancestry, respectively. Information concerning functional gene-sets
      was retrieved from the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology,
      and the Molecular Signatures Database. Fourteen of the gene-sets or pathways
      identified in the discovery dataset were confirmed in the replication dataset.
      These include functional processes involved in transcriptional regulation and
      gene expression, synapse organization, cell adhesion, and apoptosis. For two
      genes, i.e. CTCF and CACNB2, evidence for association with schizophrenia was
      available (at the gene-level) in both the discovery study and published data from
      the Psychiatric Genomics Consortium schizophrenia study. Furthermore, these genes
      mapped to four of the 14 presently identified pathways. Several of the SNPs
      assigned to CTCF and CACNB2 have potential functional consequences, and a gene in
      close proximity to CACNB2, i.e. ARL5B, was identified as a potential gene of
      interest. Application of the present hierarchical approach thus allowed: (1)
      identification of novel biological gene-sets or pathways with potential
      involvement in the etiology of schizophrenia, as well as replication of these
      findings in an independent cohort; (2) detection of genes of interest for future
      follow-up studies; and (3) the highlighting of novel genes in previously reported
      candidate regions for schizophrenia. 

PMID- 24901514
TI  - Dysfunctional voiding.
AB  - PURPOSE OF REVIEW: Female dysfunctional voiding (FDV) is an intermittent and/or
      fluctuating flow rate due to involuntary intermittent contractions of the
      periurethral striated or levator muscles during voiding in neurologically normal
      women. Despite its codified definition, because of variable causes, there is a
      lack of established diagnostic criteria and management. The aim of this study is
      to give a comprehensive, brief review of the most recent progress in the
      diagnosis and management of FDV. RECENT FINDINGS: Currently, there is the need to
      shed light on several issues in FDV, such as the use of standardized definitions,
      diagnostic criteria, and treatment modalities. The evaluation of the progress on
      these matters within 2013 helped to define some key advances in the field of
      female functional voiding dysfunction and urinary retention. SUMMARY: In 2013,
      many diagnostic and therapeutic questions in female voiding dysfunction remain
      unsolved. However, some data began to emerge. Patients with FDV did not
      demonstrate a difference in effortful control (effortful control is the ability
      to regulate one's responses to external stimuli), but did demonstrate a higher
      rate of surgency (surgency is a trait aspect of emotional reactivity in which a
      person tends towards high levels of positive affect). Toilet training method in
      childhood does not seem to have any long-term correlation with FDV. Training with
      pelvic floor physiotherapy and biofeedback still represents the first-line
      treatment for FDV. In the management of other causes of female voiding
      dysfunction, sacral neuromodulation demonstrated a satisfying long-term efficacy
      in the treatment of nonobstructive urinary retention.

PMID- 24901515
TI  - Urinary retention in women.
AB  - PURPOSE OF REVIEW: This review is a summary of the most pertinent published
      studies in the literature in the last 18 months that address cause, diagnosis,
      and management of urinary retention in women. RECENT FINDINGS: Symptoms, uroflow,
      and pressure-flow studies have a low predictive value for and do not correlate
      with elevated postvoid residual urine (PVR). Anterior and posterior colporrhaphy
      do not cause de-novo bladder outlet obstruction in the majority of patients with
      elevated PVR, and the cause of elevated PVR may be other factors such as pain or
      anxiety causing abnormal relaxation of the pelvic floor and contributing to
      voiding difficulty. The risk of urinary retention in a future pregnancy after mid
      urethral sling (MUS) is small. The risk of urinary tract infection and urinary
      retention after chemodenervation of the bladder with onabotulinumtoxin-A (100 IU)
      in patients with non-neurogenic urge incontinence is 33 and 5%, respectively.
      There is a lack of consensus among experts on the timing of sling takedown in the
      management of acute urinary retention following MUS procedures. SUMMARY: There
      has been a significant progress in the understanding of the causation of urinary
      retention. Important areas that need further research (basic and clinical) are
      post-MUS and pelvic organ prolapse repair urinary retention and obstruction, and
      urinary retention owing to detrusor underactivity.

PMID- 24901516
TI  - Bladder neck contractures and the prostate cancer survivor.
AB  - PURPOSE OF REVIEW: To summarize the cause and diagnostic and treatment concerns
      for bladder neck contractures (BNCs) in the prostate cancer survivor. RECENT
      FINDINGS: BNC rates have decreased significantly in the last 2 decades, likely
      because of improvement in the surgical technique and increased utilization of
      laparoscopic and robotic surgery, which may allow better visualization of the
      vesicourethral anastomosis. Despite these improvements, risk factors such as
      smoking and coronary artery disease contribute to BNC development. Furthermore,
      although recent reports have questioned the classical tenets of anastomotic
      technique such as water-tight anastomoses, there is no evidence that these
      principles contribute to the risk of BNC development and should continue to be
      observed. The results of minimally invasive procedures such as urethral dilation
      and transurethral incision of the bladder neck may be improved with the use of
      injectable agents. SUMMARY: There is little consensus regarding BNC therapy.
      Although several risk factors contributing to BNC development have been
      identified, strategies to reduce the risk are unclear. A number of therapeutic
      options are available, however. In the event of BNC development, treatment should
      be structured in a hierarchical fashion which minimizes the risk of urinary
      incontinence.

PMID- 24901517
TI  - Nutrition for recovery in aquatic sports.
AB  - Postexercise recovery is an important topic among aquatic athletes and involves
      interest in the quality, quantity, and timing of intake of food and fluids after
      workouts or competitive events to optimize processes such as refueling,
      rehydration, repair, and adaptation. Recovery processes that help to minimize the
      risk of illness and injury are also important but are less well documented.
      Recovery between workouts or competitive events may have two separate goals: (a)
      restoration of body losses and changes caused by the first session to restore
      performance for the next and (b) maximization of the adaptive responses to the
      stress provided by the session to gradually make the body become better at the
      features of exercise that are important for performance. In some cases, effective
      recovery occurs only when nutrients are supplied, and an early supply of
      nutrients may also be valuable in situations in which the period immediately
      after exercise provides an enhanced stimulus for recovery. This review summarizes
      contemporary knowledge of nutritional strategies to promote glycogen resynthesis,
      restoration of fluid balance, and protein synthesis after different types of
      exercise stimuli. It notes that some scenarios benefit from a proactive approach
      to recovery eating, whereas others may not need such attention. In fact, in some
      situations it may actually be beneficial to withhold nutritional support
      immediately after exercise. Each athlete should use a cost-benefit analysis of
      the approaches to recovery after different types of workouts or competitive
      events and then periodize different recovery strategies into their training or
      competition programs. 

PMID- 24901518
TI  - Progastrin represses the alternative activation of human macrophages and
      modulates their influence on colon cancer epithelial cells.
AB  - Macrophage infiltration is a negative prognostic factor for most cancers but
      gastrointestinal tumors seem to be an exception. The effect of macrophages on
      cancer progression depends on their phenotype, which may vary between M1 (pro
      inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal
      cancers often become an ectopic source of gastrins and macrophages present
      receptors for these peptides. The aim of the present study is to analyze whether
      gastrins can affect the pattern of macrophage infiltration in colorectal tumors.
      We have evaluated the relationship between gastrin expression and the pattern of
      macrophage infiltration in samples from colorectal cancer and the influence of
      these peptides on the phenotype of macrophages differentiated from human
      peripheral monocytes in vitro. The total number of macrophages (CD68+ cells) was
      similar in tumoral and normal surrounding tissue, but the number of M2
      macrophages (CD206+ cells) was significantly higher in the tumor. However, the
      number of these tumor-associated M2 macrophages correlated negatively with the
      immunoreactivity for gastrin peptides in tumor epithelial cells. Macrophages
      differentiated from human peripheral monocytes in the presence of progastrin
      showed lower levels of M2-markers (CD206, IL10) with normal amounts of M1-markers
      (CD86, IL12). Progastrin induced similar effects in mature macrophages treated
      with IL4 to obtain a M2-phenotype or with LPS plus IFNgamma to generate M1
      macrophages. Macrophages differentiated in the presence of progastrin presented a
      reduced expression of Wnt ligands and decreased the number and increased cell
      death of co-cultured colorectal cancer epithelial cells. Our results suggest that
      progastrin inhibits the acquisition of a M2-phenotype in human macrophages. This
      effect exerted on tumor associated macrophages may modulate cancer progression
      and should be taken into account when analyzing the therapeutic value of gastrin
      immunoneutralization. 

PMID- 24901519
TI  - Effects of varying gravity levels in parabolic flight on the size-mass illusion.
AB  - When an observer lifts two objects with the same weight but different sizes, the
      smaller object is consistently reported to feel heavier than the larger object
      even after repeated trials. Here we explored the effect of reduced and increased
      gravity on this perceptual size-mass illusion. Experiments were performed on
      board the CNES Airbus A300 Zero-G during parabolic flights eliciting repeated
      exposures to short periods of zero g, 0.16 g, 0.38 g, one g, and 1.8 g. Subjects
      were asked to assess perceived heaviness by actively oscillating objects with
      various sizes and masses. The results showed that a perceptual size-mass illusion
      was clearly present at all gravity levels. During the oscillations, the peak arm
      acceleration varied as a function of the gravity level, irrespective of the mass
      and size of the objects. In other words we did not observe a sensorimotor size
      mass illusion. These findings confirm dissociation between the sensorimotor and
      perceptual systems for determining object mass. In addition, they suggest that
      astronauts on the Moon or Mars with the eyes closed will be able to accurately
      determine the relative difference in mass between objects. 

PMID- 24901520
TI  - The routine utilization of dental care during pregnancy in eastern China and the
      key underlying factors: a Hangzhou City study.
AB  - OBJECTIVES: Oral diseases are associated with adverse pregnancy outcomes. The
      routine utilization of dental care (RUDC) during pregnancy is an effective way to
      improve pregnant women's oral health, and thus safeguard the health of their
      babies. As China has one fifth of the world's population, it is especially
      meaningful to encourage RUDC there. However, the status of RUDC in China and the
      key underlying factors are largely unknown. METHODS: This cross-sectional survey
      investigated the current status of RUDC during pregnancy and the key underlying
      factors in Hangzhou City, Zhejiang Province, eastern China. We collected
      participants' demographics, individual oral-hygiene behaviors, individual
      lifestyle, oral-health conditions and attitudes, and also their RUDC during
      pregnancy. Binary Logistic Regression Analysis was used to analyze the key
      underlying factors. RESULTS: Only 16.70% of the participants reported RUDC during
      pregnancy. The percentage of RUDC was significantly lower among pregnant women
      with the following characteristics: aged 30 or less, an annual household income
      under $8,000, brushing once a day or less, never flossing or rinsing the mouth,
      paying no attention to pregnancy-related oral-health knowledge, and being
      dissatisfied with one's individual dental hygiene behavior. CONCLUSIONS: RUDC
      during pregnancy is very low in eastern China and is greatly influenced not only
      by a woman's age, annual income, individual hygiene behavior, but also by her
      attention and attitudes to oral health. To improve this population's access to
      and use of dental care during pregnancy, appropriate programs and policies are
      urgently needed.

PMID- 24901521
TI  - A protein-conjugate approach to develop a monoclonal antibody-based antigen
      detection test for the diagnosis of human brucellosis.
AB  - Human brucellosis is most commonly diagnosed by serology based on agglutination
      of fixed Brucella abortus as antigen. Nucleic acid amplification techniques have
      not proven capable of reproducibly and sensitively demonstrating the presence of
      Brucella DNA in clinical specimens. We sought to optimize a monoclonal antibody
      based assay to detect Brucella melitensis lipopolysaccharide in blood by
      conjugating B. melitensis LPS to keyhole limpet hemocyanin, an immunogenic
      protein carrier to maximize IgG affinity of monoclonal antibodies. A panel of
      specific of monoclonal antibodies was obtained that recognized both B. melitensis
      and B. abortus lipopolysaccharide epitopes. An antigen capture assay was
      developed that detected B. melitensis in the blood of experimentally infected
      mice and, in a pilot study, in naturally infected Peruvian subjects. As a proof
      of principle, a majority (7/10) of the patients with positive blood cultures had
      B. melitensis lipopolysaccharide detected in the initial blood specimen obtained.
      One of 10 patients with relapsed brucellosis and negative blood culture had a
      positive serum antigen test. No seronegative/blood culture negative patients had
      a positive serum antigen test. Analysis of the pair of monoclonal antibodies
      (2D1, 2E8) used in the capture ELISA for potential cross-reactivity in the
      detection of lipopolysaccharides of E. coli O157:H7 and Yersinia enterocolitica
      O9 showed specificity for Brucella lipopolysaccharide. This new approach to
      develop antigen-detection monoclonal antibodies against a T cell-independent
      polysaccharide antigen based on immunogenic protein conjugation may lead to the
      production of improved rapid point-of-care-deployable assays for the diagnosis of
      brucellosis and other infectious diseases. 

PMID- 24901522
TI  - Deciphering the origin of the 2012 cholera epidemic in Guinea by integrating
      epidemiological and molecular analyses.
AB  - Cholera is typically considered endemic in West Africa, especially in the
      Republic of Guinea. However, a three-year lull period was observed from 2009 to
      2011, before a new epidemic struck the country in 2012, which was officially
      responsible for 7,350 suspected cases and 133 deaths. To determine whether
      cholera re-emerged from the aquatic environment or was rather imported due to
      human migration, a comprehensive epidemiological and molecular survey was
      conducted. A spatiotemporal analysis of the national case databases established
      Kaback Island, located off the southern coast of Guinea, as the initial focus of
      the epidemic in early February. According to the field investigations, the index
      case was found to be a fisherman who had recently arrived from a coastal district
      of neighboring Sierra Leone, where a cholera outbreak had recently occurred. MLVA
      based genotype mapping of 38 clinical Vibrio cholerae O1 El Tor isolates sampled
      throughout the epidemic demonstrated a progressive genetic diversification of the
      strains from a single genotype isolated on Kaback Island in February, which
      correlated with spatial epidemic spread. Whole-genome sequencing characterized
      this strain as an "atypical" El Tor variant. Furthermore, genome-wide SNP-based
      phylogeny analysis grouped the Guinean strain into a new clade of the third wave
      of the seventh pandemic, distinct from previously analyzed African strains and
      directly related to a Bangladeshi isolate. Overall, these results highly suggest
      that the Guinean 2012 epidemic was caused by a V. cholerae clone that was likely
      imported from Sierra Leone by an infected individual. These results indicate the
      importance of promoting the cross-border identification and surveillance of
      mobile and vulnerable populations, including fishermen, to prevent, detect and
      control future epidemics in the region. Comprehensive epidemiological
      investigations should be expanded to better understand cholera dynamics and
      improve disease control strategies throughout the African continent. 

PMID- 24901525
TI  - 2,2',2''-Terpyridine-catalyzed synthesis of cyclic carbonates from epoxides and
      carbon dioxide under solvent-free conditions.
AB  - An efficient coupling reaction of epoxides with CO2 affording cyclic carbonates
      with the use of 2,2',2''-terpyridine as catalyst under solvent-free conditions
      has been developed. 

PMID- 24901523
TI  - BdlA, DipA and induced dispersion contribute to acute virulence and chronic
      persistence of Pseudomonas aeruginosa.
AB  - The human pathogen Pseudomonas aeruginosa is capable of causing both acute and
      chronic infections. Differences in virulence are attributable to the mode of
      growth: bacteria growing planktonically cause acute infections, while bacteria
      growing in matrix-enclosed aggregates known as biofilms are associated with
      chronic, persistent infections. While the contribution of the planktonic and
      biofilm modes of growth to virulence is now widely accepted, little is known
      about the role of dispersion in virulence, the active process by which biofilm
      bacteria switch back to the planktonic mode of growth. Here, we demonstrate that
      P. aeruginosa dispersed cells display a virulence phenotype distinct from those
      of planktonic and biofilm cells. While the highest activity of cytotoxic and
      degradative enzymes capable of breaking down polymeric matrix components was
      detected in supernatants of planktonic cells, the enzymatic activity of dispersed
      cell supernatants was similar to that of biofilm supernatants. Supernatants of
      non-dispersing DeltabdlA biofilms were characterized by a lack of many of the
      degradative activities. Expression of genes contributing to the virulence of P.
      aeruginosa was nearly 30-fold reduced in biofilm cells relative to planktonic
      cells. Gene expression analysis indicated dispersed cells, while dispersing from
      a biofilm and returning to the single cell lifestyle, to be distinct from both
      biofilm and planktonic cells, with virulence transcript levels being reduced up
      to 150-fold compared to planktonic cells. In contrast, virulence gene transcript
      levels were significantly increased in non-dispersing DeltabdlA and DeltadipA
      biofilms compared to wild-type planktonic cells. Despite this, bdlA and dipA
      inactivation, resulting in an inability to disperse in vitro, correlated with
      reduced pathogenicity and competitiveness in cross-phylum acute virulence models.
      In contrast, bdlA inactivation rendered P. aeruginosa more persistent upon
      chronic colonization of the murine lung, overall indicating that dispersion may
      contribute to both acute and chronic infections. 

PMID- 24901524
TI  - Standardising the lactulose mannitol test of gut permeability to minimise error
      and promote comparability.
AB  - BACKGROUND: Lactulose mannitol ratio tests are clinically useful for assessing
      disorders characterised by changes in gut permeability and for assessing mixing
      in the intestinal lumen. Variations between currently used test protocols
      preclude meaningful comparisons between studies. We determined the optimal
      sampling period and related this to intestinal residence. METHODS: Half-hourly
      lactulose and mannitol urinary excretions were determined over 6 hours in 40
      healthy female volunteers after administration of either 600 mg aspirin or
      placebo, in randomised order at weekly intervals. Gastric and small intestinal
      transit times were assessed by the SmartPill in 6 subjects from the same
      population. Half-hourly percentage recoveries of lactulose and mannitol were
      grouped on a basis of compartment transit time. The rate of increase or decrease
      of each sugar within each group was explored by simple linear regression to
      assess the optimal period of sampling. KEY RESULTS: The between subject standard
      errors for each half-hourly lactulose and mannitol excretion were lowest, the
      correlation of the quantity of each sugar excreted with time was optimal and the
      difference between the two sugars in this temporal relationship maximal during
      the period from 21/2-4 h after ingestion. Half-hourly lactulose excretions were
      generally increased after dosage with aspirin whilst those of mannitol were
      unchanged as was the temporal pattern and period of lowest between subject
      standard error for both sugars. CONCLUSION: The results indicate that between
      subject variation in the percentage excretion of the two sugars would be
      minimised and the differences in the temporal patterns of excretion would be
      maximised if the period of collection of urine used in clinical tests of small
      intestinal permeability were restricted to 21/2-4 h post dosage. This period
      corresponds to a period when the column of digesta column containing the probes
      is passing from the small to the large intestine.

PMID- 24901526
TI  - Morphology, composition, and bioactivity of strontium-doped brushite coatings
      deposited on titanium implants via electrochemical deposition.
AB  - Surface modification techniques have been applied to generate titanium implant
      surfaces that promote osseointegration for use in dental applications. In this
      study, strontium-doped brushite coatings were deposited on titanium by
      electrochemical deposition. The phase composition of the coating was investigated
      by energy dispersive X-ray spectroscopy and X-ray diffraction. The surface
      morphologies of the coatings were studied through scanning electron microscopy,
      and the cytocompatibility and bioactivity of the strontium-doped brushite
      coatings were evaluated using cultured osteoblasts. Osteoblast proliferation was
      enhanced by the addition of strontium, suggesting a possible mechanism by which
      strontium incorporation in brushite coatings increased bone formation surrounding
      the implants. Cell growth was also strongly influenced by the composition of the
      deposited coatings, with a 10% Sr-doped brushite coating inducing the greatest
      amount of bone formation among the tested materials. 

PMID- 24901527
TI  - Characterization of two homogalacturonan pectins with immunomodulatory activity
      from green tea.
AB  - Two natural homogalacturonan (HG) pectins (MW ca. 20 kDa) were isolated from
      green tea based on their immunomodulatory activity. The crude tea polysaccharides
      (TPS1 and TPS2) were obtained from green tea leaves by hot water extraction and
      followed by 40% and 70% ethanol precipitation, respectively. Two homogenous water
      soluble polysaccharides (TPS1-2a and TPS1-2b) were obtained from TPS1 after
      purification with gel permeation, which gave a higher phagocytic effect than
      TPS2. A combination of composition, methylation and configuration analyses, as
      well as NMR (nuclear magnetic resonance) spectroscopy revealed that TPS1-2a and
      TPS1-2b were homogalacturonan (HG) pectins consisting of a backbone of 1,4-linked
      alpha-D-galacturonic acid (GalA) residues with 28.4% and 26.1% of carboxyl groups
      as methyl ester, respectively. The immunological assay results demonstrated that
      TPS1-2, which consisted mainly of HG pectins, showed phagocytosis-enhancing
      activity in HL-60 cells.

PMID- 24901528
TI  - Selective isolation of trypsin inhibitor and lectin from soybean whey by
      chitosan/tripolyphosphate/genipin co-crosslinked beads.
AB  - Selective isolation of Kunitz trypsin inhibitor (KTI) and lectin from soybean
      whey solutions by different types of chitosan beads was investigated. The
      chitosan beads were co-crosslinked with tripolyphosphate/genipin in solutions at
      pH 5, 7 or 9 (CB5, CB7, CB9). The maximum adsorption ratios of chitosan beads to
      KTI and lectin were observed at pH 4.4 and 5.4, respectively; highly selective
      separation was also demonstrated at these pHs. The adsorption ratios increased
      with temperature, rising between 5 and 25  degrees C. CB9 produced the best
      adsorption ratio, followed by CB7 then CB5. The critical interaction governing
      absorption of chitosan beads to KTI and lectin could be hydrogen bonding. At pH
      9, KTI and lectin desorbed efficiently from CB7 with desorption ratios of 80.9%
      and 81.4%, respectively. The desorption was most likely caused predominantly by
      electrostatic repulsion. KTI and lectin can effectively be selectively isolated
      from soybean whey using this novel separation technique. 

PMID- 24901529
TI  - Concentration of antifouling biocides and metals in sediment core samples in the
      northern part of Hiroshima Bay.
AB  - Accumulation of Ot alternative antifoulants in sediment is the focus of this
      research. Much research had been done on surface sediment, but in this report,
      the accumulation in the sediment core was studied. The Ot alternative
      antifoulants, Diuron, Sea-Nine211, and Irgarol 1051, and the latter's degradation
      product, M1, were investigated in five samples from the northern part of
      Hiroshima Bay. Ot compounds (tributyltin (TBT) and triphenyltin (TPT)) were also
      investigated for comparison. In addition, metal (Pb, Cu, Zn, Fe and Mn) levels
      and chronology were measured to better understand what happens after accumulation
      on the sea floor. It was discovered that Ot alternative antifoulant accumulation
      characteristics in sediment were like Ot compounds, with the concentration in the
      sediment core being much higher than surface sediment. The concentration in
      sediment seems to have been affected by the regulation of Ot compounds in 1990,
      due to the concentration of Ot alternative antifoulants and Ot compounds at the
      survey point in front of the dock, showing an increase from almost the same layer
      after the regulation. 

PMID- 24901530
TI  - Elucidation of the specific formation of homo- and heterodimeric forms of ThbZIP1
      and its role in stress.
AB  - Protein-protein interactions are important for the molecular understanding of the
      biological processes of proteins. The dimerization of bZIPs (basic leucine zipper
      proteins) is involved in modifying binding site specificities, altering dimer
      stability, and permitting a new set of specific protein-to-protein interactions
      to occur at the promoter. In the present study, we studied the whether ThbZIP1
      form homo- and heterodimers using the yeast two-hybrid method. Five bZIP genes
      were cloned from Tamarix hispida to investigate their interaction with ThbZIP1.
      Our results showed that ThbZIP1 can form homodimers with itself, and three out of
      five bZIPs could interact with the ThbZIP1 protein to form heterodimers. Real
      time RT-PCR results suggested that these ThbZIPs can all respond to abiotic
      stresses and abscisic acid (ABA), and shared very similar expression patterns in
      response to NaCl, ABA or PEG6000. Subcellular localization studies showed that
      all ThbZIPs are targeted to the nucleus. Our results showed that ThbZIP1 are
      dimeric proteins, which can form homo- or heterodimers. 

PMID- 24901531
TI  - A new criterion to evaluate water vapor interference in protein secondary
      structural analysis by FTIR spectroscopy.
AB  - Second derivative and Fourier self-deconvolution (FSD) are two commonly used
      techniques to resolve the overlapped component peaks from the often featureless
      amide I band in Fourier transform infrared (FTIR) curve-fitting approach for
      protein secondary structural analysis. Yet, the reliability of these two
      techniques is greatly affected by the omnipresent water vapor in the atmosphere.
      Several criteria are currently in use as quality controls to ensure the protein
      absorption spectrum is negligibly affected by water vapor interference. In this
      study, through a second derivative study of liquid water, we first argue that the
      previously established criteria cannot guarantee a reliable evaluation of water
      vapor interference due to a phenomenon that we refer to as sample's absorbance
      dependent water vapor interference. Then, through a comparative study of protein
      and liquid water, we show that a protein absorption spectrum can still be
      significantly affected by water vapor interference even though it satisfies the
      established criteria. At last, we propose to use the comparison between the
      second derivative spectra of protein and liquid water as a new criterion to
      better evaluate water vapor interference for more reliable second derivative and
      FSD treatments on the protein amide I band. 

PMID- 24901532
TI  - Migration and interaction in a contact zone: mtDNA variation among Bantu-speakers
      in Southern Africa.
AB  - Bantu speech communities expanded over large parts of sub-Saharan Africa within
      the last 4000-5000 years, reaching different parts of southern Africa 1200-2000
      years ago. The Bantu languages subdivide in several major branches, with
      languages belonging to the Eastern and Western Bantu branches spreading over
      large parts of Central, Eastern, and Southern Africa. There is still debate
      whether this linguistic divide is correlated with a genetic distinction between
      Eastern and Western Bantu speakers. During their expansion, Bantu speakers would
      have come into contact with diverse local populations, such as the Khoisan hunter
      gatherers and pastoralists of southern Africa, with whom they may have
      intermarried. In this study, we analyze complete mtDNA genome sequences from over
      900 Bantu-speaking individuals from Angola, Zambia, Namibia, and Botswana to
      investigate the demographic processes at play during the last stages of the Bantu
      expansion. Our results show that most of these Bantu-speaking populations are
      genetically very homogenous, with no genetic division between speakers of Eastern
      and Western Bantu languages. Most of the mtDNA diversity in our dataset is due to
      different degrees of admixture with autochthonous populations. Only the
      pastoralist Himba and Herero stand out due to high frequencies of particular L3f
      and L3d lineages; the latter are also found in the neighboring Damara, who speak
      a Khoisan language and were foragers and small-stock herders. In contrast, the
      close cultural and linguistic relatives of the Herero and Himba, the Kuvale, are
      genetically similar to other Bantu-speakers. Nevertheless, as demonstrated by
      resampling tests, the genetic divergence of Herero, Himba, and Kuvale is
      compatible with a common shared ancestry with high levels of drift, while the
      similarity of the Herero, Himba, and Damara probably reflects admixture, as also
      suggested by linguistic analyses. 

PMID- 24901534
TI  - Stoichiometry-controlled two flexible interpenetrated frameworks: higher CO2
      uptake in a nanoscale counterpart supported by accelerated adsorption kinetics.
AB  - Here, we report the synthesis, structural characterizations, and gas storage
      properties of two new 2-fold interpenetrated 3D frameworks,
      {[Zn2(bpdc)2(azpy)].2H2O.2DMF}n (1) and {[Zn3(bpdc)3(azpy)].4H2O.2DEF}n (2) [bpdc
      = 4,4'-biphenyldicarboxylate; azpy = 4,4'-azobipyridine], obtained from the same
      set of organic linkers. Furthermore, 1 has been successfully miniaturized to
      nanoscale (MOF1N) of spherical morphology to study size dependent adsorption
      properties through a coordination modulation method. The two different SBUs,
      dinuclear paddle-wheel {Zn2(COO)4} for 1 and trinuclear {Zn3(MU2-OCO)2(COO)4 }for
      2, direct the different network topologies of the frameworks that render
      different adsorption characteristics into the systems. Both of the frameworks
      show guest induced structural transformations as supported by PXRD studies.
      Adsorption studies of 1 and 2 show CO2 selectivity over several other gases (such
      as N2, H2, O2, and Ar) under identical experimental conditions. Interestingly,
      MOF1N exhibits significantly higher CO2 storage capacity compared to bulk
      crystals of 1 and that can be attributed to the smaller diffusion barrier at the
      nanoscale that is supported by studies of adsorption kinetics in both states.
      Kinetic measurement based on water vapor adsorption clearly distinguishes between
      the rate of diffusion of bulk (1) and nanospheres (MOF1N). The respective kinetic
      rate constant (k, s(-1)) for MOF1N (k = 1.29 * 10(-2) s(-1)) is found to be
      considerably higher than 1 (k = 7.1 * 10(-3) s(-1)) as obtained from the linear
      driving force (LDF) model. This is the first account where a new interpenetrated
      MOF has been scaled down to nanoscale through a coordination modulation method,
      and their difference in gas uptake properties has been correlated through a
      higher rate of mass diffusion as obtained from kinetics of adsorption. 

PMID- 24901533
TI  - NMR characterization of the interaction of the endonuclease domain of MutL with
      divalent metal ions and ATP.
AB  - MutL is a multi-domain protein comprising an N-terminal ATPase domain (NTD) and C
      terminal dimerization domain (CTD), connected with flexible linker regions, that
      plays a key role in DNA mismatch repair. To expand understanding of the
      regulation mechanism underlying MutL endonuclease activity, our NMR-based study
      investigated interactions between the CTD of MutL, derived from the
      hyperthermophilic bacterium Aquifex aeolicus (aqMutL-CTD), and putative binding
      molecules. Chemical shift perturbation analysis with the model structure of
      aqMutL-CTD and circular dichroism results revealed that tight Zn(2+) binding
      increased thermal stability without changing secondary structures to function at
      high temperatures. Peak intensity analysis exploiting the paramagnetic relaxation
      enhancement effect indicated the binding site for Mn(2+), which shared binding
      sites for Zn(2+). The coexistence of these two metal ions appears to be important
      for the function of MutL. Chemical shift perturbation analysis revealed a novel
      ATP binding site in aqMutL-CTD. A docking simulation incorporating the chemical
      shift perturbation data provided a putative scheme for the intermolecular
      interactions between aqMutL-CTD and ATP. We proposed a simple and understandable
      mechanical model for the regulation of MutL endonuclease activity in MMR based on
      the relative concentrations of ATP and CTD through ATP binding-regulated
      interdomain interactions between CTD and NTD.

PMID- 24901535
TI  - DTI analysis in patients with primary open-angle glaucoma: impact of registration
      on Voxel-Wise statistics.
AB  - BACKGROUND AND PURPOSE: Tract-based spatial statistics (TBSS) has been used to
      assess the integrity of the visual pathway in glaucoma patients. TBSS uses the
      subjects' FA data to create a mean FA skeleton of white matter tracts before
      running voxel-wise cross-subject statistics. We compared four different
      approaches of registration of FA maps to create the skeleton and evaluated
      alignment and subsequently the impact of the chosen registration on voxel-wise
      statistics. MATERIAL AND METHODS: Our study comprised 69 subjects, i.e. 46
      patients with primary open angle glaucoma (POAG) and a healthy, age-matched
      control group of 23 subjects. Mean FA skeletons were created using the following
      registration approaches: registration to a standard template (T), registration to
      the group mean (GM), registration to a group-wise atlas (GW) and registration to
      the most typical subject (N). Subsequently, maps of standard deviation of the 4D
      images were created to assess the alignment. Voxel-wise statistics for each
      registration approach were performed. RESULTS: We found distinct differences in
      voxel-wise statistics depending on the chosen registration approach. Best
      alignment results were achieved by registration to a study specific template,
      i.e. to the group mean (GM) or to a group-wise atlas (GW). Overall alignment did
      not differ between these two approaches. However, voxel-wise statistics showed
      clusters of significantly decreased FA values in the T and GM approach, which
      were not significant after GW registration. These voxels of significantly
      decreased FA values after T and GM registration did not represent white matter
      tracts and correlated with higher standard deviation in FA maps across subjects,
      thus implying registration errors, especially in the optic radiation. CONCLUSION:
      Registration to a study-specific template, i.e. to the group mean or a group-wise
      atlas seems to be the method of choice in TBSS-analysis of glaucoma patients as
      it shows better alignment of the optic radiation and helps to rule out
      registration errors due to misalignment.

PMID- 24901536
TI  - The role of plastic surgeon in complex cephalic malformations. Our experience.
AB  - AIM: Our aim is focused on the field of action of plastic surgery in the cephalic
      malformation and on description of the surgical indications and techniques for
      their correction. MATERIAL OF STUDY: We looked at 27 patients from 2006 to 2012
      with cephalic district deformities. All patients underwent surgical and
      rehabilitative treatments. RESULTS: After a median follow-up from one to five
      years, in most cases we reached both morphological and functional reconstruction,
      alone or in a surgical team together with other surgical disciplines. DISCUSSION:
      The correction of craniofacial malformations makes use of a surgical discipline
      particularly demanding, which must associate a basic surgical training with a
      learning techniques specific to the area and a knowledge of craniofacial
      malformation. CONCLUSIONS: The surgical treatment of craniofacial malformations
      can be seen only through a joint neurosurgical and plastic-maxillo-facial
      surgery, guided by knowledge of the malformation, under the close supervision of
      anesthetists and pediatricians. This surgery is not limited to remodel the
      morphology but has its bases on the recovery of the functions, maintained by
      rehabilitation treatment.

PMID- 24901539
TI  - Chemoenzymatic convergent synthesis of 2'-O,4'-C-methyleneribonucleosides.
AB  - Novozyme-435-catalyzed efficient regioselective acetylation of one of the two
      diastereotopic hydroxymethyl functions in 3-O-benzyl-4-C-hydroxymethyl-1,2-O
      isopropylidene-alpha-d-ribofuranose has been achieved. The enzymatic methodology
      has been successfully utilized for convergent synthesis of bicyclic nucleosides
      (LNA monomers) T, U, A, and C. Further, it has been demonstrated that Novozyme
      435 can be used for 10 cycles of the acylation reaction without losing
      selectivity and efficiency. 

PMID- 24901540
TI  - Stepwise synthesis of a stable diphosphasilirane and its unexpected dimerization.
AB  - The synthesis of the thermally stable bicyclic diphosphasilirane
      O(SiiPr2P)2SiiPr2 (4) was achieved via oxidation of the alkaline earth metal
      substituted cyclic diphosphanide 3 with 1,2-dibromoethane. Nonetheless, during
      extended storage at low temperature, impurity induced rearrangement in favour of
      the dimeric species [O(SiiPr2P)2SiiPr2]2 (5) is observed.

PMID- 24901538
TI  - Proteomic changes in serum of first onset, antidepressant drug-naive major
      depression patients.
AB  - Major depressive disorder (MDD) is a complex and multi-factorial disorder.
      Although genetic factors and other molecular aspects of MDD have been widely
      studied, the underlying pathological mechanisms are still mostly unknown. We
      sought to investigate the pathophysiology of MDD by identifying and
      characterising serum molecular differences and their correlation to symptom
      severity in first onset, antidepressant drug-naive MDD patients. We performed an
      exploratory molecular profiling study on serum samples of MDD patients and
      controls using multiplex immunoassay and label-free liquid chromatography mass
      spectrometry in data independent mode (LC-MSE). We included two independent
      cohorts of first onset, antidepressant drug-naive MDD patients (n = 23 and 15)
      and matched controls (n = 42 and 21) in our study in order to validate the
      results. The main outcome included the following list of circulatory molecules
      changing and/or correlating to symptom severity: angiotensin-converting enzyme,
      acute phase proteins (e.g. ferritin and serotransferrin), brain-derived
      neurotrophic factor, complement component C4-B, cortisol, cytokines (e.g.
      macrophage migration inhibitory factor and interleukin-16), extracellular newly
      identified receptor for advanced glycosylation end products-binding protein,
      growth hormone and superoxide dismutase-1. This study provides evidence of an
      increased pro-inflammatory and oxidative stress response, followed by a
      hyperactivation of the HPA-axis in the acute stages of first onset MDD, as well
      as a dysregulation in growth factor pathways. These findings help to elucidate
      MDD related pathways in more detail and further studies may lead to
      identification of novel drug targets, including components of the inflammatory
      and oxidative stress response. 

PMID- 24901541
TI  - What is the Ability Emotional Intelligence Test (MSCEIT) good for? An evaluation
      using item response theory.
AB  - The ability approach has been indicated as promising for advancing research in
      emotional intelligence (EI). However, there is scarcity of tests measuring EI as
      a form of intelligence. The Mayer Salovey Caruso Emotional Intelligence Test, or
      MSCEIT, is among the few available and the most widespread measure of EI as an
      ability. This implies that conclusions about the value of EI as a meaningful
      construct and about its utility in predicting various outcomes mainly rely on the
      properties of this test. We tested whether individuals who have the highest
      probability of choosing the most correct response on any item of the test are
      also those who have the strongest EI ability. Results showed that this is not the
      case for most items: The answer indicated by experts as the most correct in
      several cases was not associated with the highest ability; furthermore, items
      appeared too easy to challenge individuals high in EI. Overall results suggest
      that the MSCEIT is best suited to discriminate persons at the low end of the
      trait. Results are discussed in light of applied and theoretical considerations. 

PMID- 24901542
TI  - [The forthcoming history of leprosy].

PMID- 24901543
TI  - [150 years Lungenheilstatte Gorbersdorf (Sokolowsko)].

PMID- 24901544
TI  - ["Nutritional risk screening 2002"--in clinical pneumology].
AB  - Malnutrition is a frequent problem for hospitalized patients. It is a relevant
      risk factor for morbidity and mortality. The aim of this study was to detect
      undernutrition and the risk of malnutrition (RM) in patients admitted to a
      university-affiliated respiratory care clinic. Undernutrition was assessed by
      body mass index (BMI<18.5 kg/m2) and RM by using the "Nutritional Risk Screening
      2002" (NRS 2002) in 705 consecutive patients (BMI: measured in 689 patients/NRS:
      680 patients assessed). Data was analysed with regard to age, sex, length of
      hospital stay as well as underlying pneumological disorders. In 14.3% of 680
      patients, RM was detected by NRS. In 2.5% out of 689 patients, undernutrition was
      identified by BMI. In patients older than 65 years (n=365), these numbers were
      19.6% (NRS) and 1.5% (BMI<18.5 kg/m2). Age was a significant risk factor for RM
      (OR 1.054 per year). Gender, however, was not associated with undernutrition or
      RM. In a sub-analysis, RM was more frequent in patients with pneumonia and
      chronic obstructive lung disease (23% and 16%, respectively). Patients with
      cancer were more frequently at RM as compared to patients with sleep-disordered
      breathing (OR: 2.33 in cancer, OR: 0.04 in sleep-disordered breathing). RM was
      associated with a significant increase in length of hospital stay (10.2 +/- 9.5
      vs. 5.4 +/- 6.0 days). Besides the BMI, the NRS provides a valid tool for
      screening patients at RM.

PMID- 24901546
TI  - Dynamic contrast-enhanced magnetic resonance imaging assessment of kidney
      function and renal masses: single slice versus whole organ/tumor.
AB  - OBJECTIVES: The aim of this study was to compare single-slice and 3-dimensional
      (3D) analysis for magnetic resonance renography (plasma flow [FP], plasma volume
      [VP], and glomerular filtration rate [GFR]) and for dynamic contrast-enhanced
      magnetic resonance imaging (MRI) of renal tumors (FP, VP, permeability-surface
      area product), respectively. MATERIAL AND METHODS: We prospectively included 22
      patients (43 kidneys with 22 suspicious renal lesions) and performed preoperative
      and postoperative imaging before and after partial nephrectomy, respectively. Of
      the 22 renal lesions, 15 turned out to be renal cell carcinoma and were included
      in the tumor analysis, altogether leading to 86 renal and 15 tumor MRI scans,
      respectively. Dynamic contrast-enhanced MRI was performed with a time-resolved
      angiography with stochastic trajectories sequence (spatial resolution, 2.6 * 2.6
      * 2.6 mm3; temporal resolution, 2.5 seconds) at 3 T (Magnetom Verio; Siemens
      Healthcare Sector) after injection of 0.05 mmol/kg body weight Gadobutrol (Bayer
      Healthcare Pharmaceuticals). Analysis was performed using regions of interest
      encompassing a single central slice and the whole kidney/tumor, respectively. A 2
      compartment model yielding FP, VP, GFR, or tumor permeability-surface area
      product was used for kinetic modelling. Modelling was performed based on relative
      contrast enhancement to account for coil-related inhomogeneity. Significance in
      difference, agreement, and goodness of fit of the data to the curve was assessed
      with paired t tests, Bland-Altman plots, and chi2 test, respectively. RESULTS:
      Bland-Altman analysis revealed a good agreement between both types of measurement
      for kidneys and tumors, respectively. Results between single-slice and whole
      kidney regions of interest showed significant differences for Fp (single slice,
      256.1 +/- 104.1 mL/100 mL/min; whole kidney, 217.2 +/- 92.5 mL/100 mL/min; P <
      0.01). Regarding VP and GFR, no significant differences were observed. The chi2
      test showed a significantly better goodness of fit of the data to the curve for
      whole kidneys (0.30% +/- 0.18%) than for single slices (0.43% +/- 0.26%) (P <
      0.01). In contrast to renal assessment, tumor analysis showed no significant
      differences regarding functional parameters and chi test, respectively.
      CONCLUSION: In dynamic contrast-enhanced MRI of the kidney, both 3D whole
      organ/tumor and single-slice analyses provide roughly comparable values in
      functional analysis. However, 3D assessment is considerably more precise and
      should be preferred if available.

PMID- 24901545
TI  - 2-tier in-plane motion correction and out-of-plane motion filtering for contrast
      enhanced ultrasound.
AB  - OBJECTIVES: Contrast-enhanced ultrasound (CEUS) cines of focal liver lesions
      (FLLs) can be quantitatively analyzed to measure tumor perfusion on a pixel-by
      pixel basis for diagnostic indication. However, CEUS cines acquired freehand and
      during free breathing cause nonuniform in-plane and out-of-plane motion from
      frame to frame. These motions create fluctuations in the time-intensity curves
      (TICs), reducing the accuracy of quantitative measurements. Out-of-plane motion
      cannot be corrected by image registration in 2-dimensional CEUS and degrades the
      quality of in-plane motion correction (IPMC). A 2-tier IPMC strategy and adaptive
      out-of-plane motion filter (OPMF) are proposed to provide a stable correction of
      nonuniform motion to reduce the impact of motion on quantitative analyses.
      MATERIALS AND METHODS: A total of 22 cines of FLLs were imaged with dual B-mode
      and contrast specific imaging to acquire a 3-minute TIC. B-mode images were
      analyzed for motion, and the motion correction was applied to both B-mode and
      contrast images. For IPMC, the main reference frame was automatically selected
      for each cine, and subreference frames were selected in each respiratory cycle
      and sequentially registered toward the main reference frame. All other frames
      were sequentially registered toward the local subreference frame. Four OPMFs were
      developed and tested: subsample normalized correlation (NC), subsample sum of
      absolute differences, mean frame NC, and histogram. The frames that were most
      dissimilar to the OPMF reference frame using 1 of the 4 above criteria in each
      respiratory cycle were adaptively removed by thresholding against the low-pass
      filter of the similarity curve. Out-of-plane motion filter was quantitatively
      evaluated by an out-of-plane motion metric (OPMM) that measured normalized
      variance in the high-pass filtered TIC within the tumor region-of-interest with
      low OPMM being the goal. Results for IPMC and OPMF were qualitatively evaluated
      by 2 blinded observers who ranked the motion in the cines before and after
      various combinations of motion correction steps. RESULTS: Quantitative
      measurements showed that 2-tier IPMC and OPMF improved imaging stability. With
      IPMC, the NC B-mode metric increased from 0.504 +/- 0.149 to 0.585 +/- 0.145 over
      all cines (P < 0.001). Two-tier IPMC also produced better fits on the contrast
      specific TIC than industry standard IPMC techniques did (P < 0.02). In-plane
      motion correction and OPMF were shown to improve goodness of fit for pixel-by
      pixel analysis (P < 0.001). Out-of-plane motion filter reduced variance in the
      contrast-specific signal as shown by a median decrease of 49.8% in the OPMM. Two
      tier IPMC and OPMF were also shown to qualitatively reduce motion. Observers
      consistently ranked cines with IPMC higher than the same cine before IPMC (P <
      0.001) as well as ranked cines with OPMF higher than when they were uncorrected.
      CONCLUSION: The 2-tier sequential IPMC and adaptive OPMF significantly reduced
      motion in 3-minute CEUS cines of FLLs, thereby overcoming the challenges of drift
      and irregular breathing motion in long cines. The 2-tier IPMC strategy provided
      stable motion correction tolerant of out-of-plane motion throughout the cine by
      sequentially registering subreference frames that bypassed the motion cycles,
      thereby overcoming the lack of a nearly stationary reference point in long cines.
      Out-of-plane motion filter reduced apparent motion by adaptively removing frames
      imaged off-plane from the automatically selected OPMF reference frame, thereby
      tolerating nonuniform breathing motion. Selection of the best OPMF by minimizing
      OPMM effectively reduced motion under a wide variety of motion patterns
      applicable to clinical CEUS. These semiautomated processes only required user
      input for region-of-interest selection and can improve the accuracy of
      quantitative perfusion measurements.

PMID- 24901547
TI  - Academic-community partnership development lessons learned: evidence-based
      interventions to increase screening mammography in rural communities.
AB  - Early detection of breast cancer leads to higher survival; yet, women who live in
      rural areas have lower screening rates and receive diagnosis at later stages.
      Effective screening approaches have been published in scientific journals but are
      not easily available to and understandable by community members. This article
      describes the development of an academic-community collaboration to implement
      evidence-based interventions to increase screening. 

PMID- 24901548
TI  - Prescription stimulants are "a okay": applying neutralization theory to college
      students' nonmedical prescription stimulant use.
AB  - OBJECTIVE: National college health data indicate that prescription stimulants are
      the most widely misused prescription drugs among college students, with 9%
      admitting to nonmedical use within the past year.(1) Although motivations for the
      nonmedical use of these drugs have been explored, scant attention has been paid
      to justifications for nonmedical use. This article fills that gap by expounding
      upon the justifications students incite to defend their nonmedical use of these
      drugs. PARTICIPANTS: Seventy-six college students from a large, public
      northwestern university. METHODS: Semistructured interviews were conducted during
      the 2010-2011 academic year. RESULTS: Inductive analysis uncovered social
      learning theories of crime/deviance, more specifically, Sykes and Matza's
      neutralization theory(2) as helping to inform justifications for nonmedical
      stimulant use. This theory was modified to better encompass the justifications
      that students employed. CONCLUSION: Justifications for use must become a more
      central part of the conversation surrounding nonmedical stimulant use among the
      college population.

PMID- 24901549
TI  - Stay the course.

PMID- 24901550
TI  - First Chinese-made biologics slated for human trials in the West.

PMID- 24901551
TI  - Cryptographic methods enable analyses without privacy breaches.

PMID- 24901552
TI  - Patent-free pact pushes the boundaries of precompetitive research.

PMID- 24901553
TI  - New platforms aim to obliterate silos of participatory science.

PMID- 24901554
TI  - Diabetes researchers fear worsening access to human islets.

PMID- 24901556
TI  - Straight talk with...Geoffrey Ling.

PMID- 24901557
TI  - The cancer-virus cures.

PMID- 24901558
TI  - Mentorship matters for the biomedical workforce.

PMID- 24901560
TI  - NGS library preparation may generate artifactual integration sites of AAV
      vectors.

PMID- 24901561
TI  - Reply to: NGS library preparation may generate artifactual integration sites of
      AAV vectors.

PMID- 24901562
TI  - Interleukin-35 takes the 'B' line.

PMID- 24901563
TI  - Young blood rejuvenates old brains.

PMID- 24901564
TI  - Lessons from babies: inducing HIV-1 broadly neutralizing antibodies.

PMID- 24901565
TI  - Cardiomyopathy, mitochondria and Barth syndrome: iPSCs reveal a connection.

PMID- 24901566
TI  - An alternative DNA damage pathway to apoptosis in hematological cancers.

PMID- 24901537
TI  - Physicochemical properties of cells and their effects on intrinsically disordered
      proteins (IDPs).

PMID- 24901567
TI  - Overcoming Drug Development Bottlenecks With Repurposing: Old drugs learn new
      tricks.

PMID- 24901568
TI  - Overcoming Drug Development Bottlenecks With Repurposing: Repurposing biguanides
      to target energy metabolism for cancer treatment.

PMID- 24901576
TI  - Exploring the relationship among user satisfaction, compliance, and clinical
      outcomes of telemedicine services for glucose control.
AB  - BACKGROUND: Although research has shown that telemedicine services for blood
      glucose control can be useful in managing diabetes, the relationships among user
      satisfaction, compliance, and clinical outcomes have not been well studied. A
      positive assessment of telemedicine services can improve user satisfaction, which
      can increase compliance and improve clinical outcomes. These relationships are
      validated with actual telemedicine projects for diabetes management. MATERIALS
      AND METHODS: The assessment of user satisfaction for telemedicine services is
      composed of the following six variables: usefulness, ease of use, compatibility,
      facilitating conditions, accessibility, and intimacy. The relationship between
      user satisfaction and compliance or hemoglobin A1c (HbA1c) improvement was
      analyzed. Data were collected from 81 type 2 diabetic patients who used
      telemedicine services. We used multiple regression analysis, logistic regression
      analysis, simple linear regression, and the Wilcoxon signed-rank test to analyze
      the data. RESULTS: The user assessments of the telemedicine services were very
      high, ranging from 5.8 to 6 points. Of the six variables, compatibility, ease of
      use, intimacy, and usefulness had a positive effect on overall satisfaction
      (p<0.05). Overall satisfaction and compliance were positively correlated with
      HbA1c improvement. In addition, income level was also an important variable for
      overall satisfaction. CONCLUSIONS: Our results indicate that patient assessments
      of telemedicine services are important factors for clinical outcome improvement.
      In addition, higher satisfaction and more frequent self-assessments can improve
      clinical outcomes.

PMID- 24901577
TI  - Pure white-light and yellow-to-blue emission tuning in single crystals of Dy(III)
      metal-organic frameworks.
AB  - Direct white-light emission was first achieved in a single phase material of a
      Dy(III) metal-organic framework, which also shows tunable yellow-to-blue
      photoluminescence upon variation of excitation wavelengths.

PMID- 24901578
TI  - Case study: Natural bodybuilding contest preparation.
AB  - The purpose of this study was to document the physiological changes that occur in
      a natural bodybuilder during prolonged contest preparation for a proqualifying
      contest. During the 26-week preparation, the athlete undertook a calorically
      restrictive diet with 2 days of elevated carbohydrate intake per week, increased
      cardiovascular (CV) training, and attempted to maintain resistance-training load.
      The athlete was weighed twice a week and body composition was measured monthly by
      DXA. At baseline and every 2 weeks following CV structure and function was
      measured using a combination of ultrasound, applanation tonometry, and heart rate
      variability (HRV). Cardiorespiratory performance was measured by VO(2)peak at
      baseline, 13 weeks, and 26 weeks. Body weight (88.6 to 73.3 Kg, R(2) = .99) and
      percent body fat (17.5 to 7.4%) were reduced during preparation. CV measurements
      including blood pressure (128/61 to 113/54 mmHg), brachial pulse wave velocity
      (7.9 to 5.8m/s), and measures of wave reflection all improved. Indexed cardiac
      output was reduced (2.5 to 1.8L/m(2)) primarily due to a reduction in resting
      heart rate (71 to 44 bpm), and despite an increase in ejection faction (57.9 to
      63.9%). Assessment of HRV found a shift in the ratio of low to high frequency
      (209.2 to 30.9%). Absolute VO2 was minimally reduced despite weight loss
      resulting in an increase in relative VO2 (41.9 to 47.7 ml/Kg). In general, this
      prolonged contest preparation technique helped the athlete to improve body
      composition and resulted in positive CV changes, suggesting that this method of
      contest preparation appears to be effective in natural male bodybuilders.

PMID- 24901579
TI  - High serum concentration of interleukin-18 in diabetic patients with foot ulcers.
AB  - BACKGROUND: It is well known that interleukin-18 (IL-18) plays a key role in the
      inflammatory process. However, there are limited data on the role IL-18 plays
      with diabetic foot ulcers, an acute and complex inflammatory situation.
      Therefore, we aimed to evaluate serum IL-18 levels of diabetic patients with foot
      ulcers. METHODS: Twenty diabetic patients with acute foot ulcers, 21 diabetic
      patients without a history of foot ulcers, and 21 healthy volunteers were
      enrolled in our study. Circulating levels of IL-18, and other biochemical markers
      are parameters of inflammation and were measured in all three groups. RESULTS:
      Diabetic patients both with and without foot ulcers had high IL-18 concentrations
      (P < 0.001 and P = 0.020, respectively) when compared with the nondiabetic
      volunteers. Those with foot ulcers had higher levels of IL-18 level (P < 0.001),
      high-sensitivity C-reactive protein (hsCRP) (P = 0.001), and erythrocyte
      sedimentation rate (ESR) (P < 0.001) than those without foot ulcers. CONCLUSIONS:
      We found that serum IL-18 concentrations were elevated in diabetic patients with
      acute diabetic foot ulcers. However, these findings do not indicate whether the
      IL-18 elevation is a cause or a result of the diabetic foot ulceration. Further
      studies are needed to show the role of IL-18 in the course of these ulcers.

PMID- 24901580
TI  - Is scintigraphy a guideline method in determining amputation levels in diabetic
      foot?
AB  - BACKGROUND: In this study, we aimed to evaluate the potential use of a 3-phase
      bone scintigraphy method to determine the level of amputation on treatment cost,
      morbidity and mortality, reamputation rates, and the duration of hospitalization
      in diabetic foot. METHODS: Thirty patients who were admitted to our clinic
      between September 2008 and July 2009, with diabetic foot were included. All
      patients were evaluated according to age, gender, diabetes duration, 3-phase bone
      scintigraphy, Doppler ultrasound, amputation/reamputation levels, and
      hospitalization periods. Patients underwent 3-phase bone scintigraphy using
      technetium-99m methylene diphosphonate, and the most distal site of the region
      displaying perfusion during the perfusion and early blood flow phase was marked
      as the amputation level. Amputation level was determined by 3-phase bone
      scintigraphy, Doppler ultrasound, and inspection of the infection-free clear
      region during surgery. RESULTS: The amputation levels of the patients were as
      follows: finger in six (20%), ray amputation in five (16.6%), transmetatarsal in
      one (3.3%), Lisfranc in two (6.6%), Chopart in seven (23.3%), Syme in one (3.3%),
      below-the-knee in six (20%), above the knee in one (3.3%), knee disarticulation
      in one (3.3%), and two patients underwent amputation at other centers. After
      primary amputation, reamputation was performed on seven patients, and one patient
      was treated with debridement for wound site problems. No mortality was
      encountered during study. CONCLUSIONS: We conclude that 3-phase bone scintigraphy
      prior to surgery could be a useful method to determine the amputation level in a
      diabetic foot. We conclude that further, comparative, more comprehensive, long
      term, and controlled studies are required.

PMID- 24901581
TI  - Using a polymerase chain reaction as a complementary test to improve the
      detection of dermatophyte fungus in nails.
AB  - BACKGROUND: Dermatomycoses are a group of pathologic abnormalities frequently
      seen in clinical practice, and their prevalence has increased in recent decades.
      Diagnostic confirmation of mycotic infection in nails is essential because there
      are several pathologic conditions with similar clinical manifestations. The
      classical method for confirming the presence of fungus in nail is microbiological
      culture and the identification of morphological structures by microscopy.
      METHODS: We devised a nested polymerase chain reaction (PCR) that amplifies
      specific DNA sequences of dermatophyte fungus that is notably faster than the 3
      to 4 weeks that the traditional procedure takes. We compared this new technique
      and the conventional plate culture method in 225 nail samples. The results were
      subjected to statistical analysis. RESULTS: We found concordance in 78.2% of the
      samples analyzed by the two methods and increased sensitivity when simultaneously
      using the two methods to analyze clinical samples. Now we can confirm the
      presence of dermatophyte fungus in most of the positive samples in just 24 hours,
      and we have to wait for the result of culture only in negative PCR cases.
      CONCLUSIONS: Although this PCR cannot, at present, substitute for the traditional
      culture method in the detection of dermatophyte infection of the nails, it can be
      used as a complementary technique because its main advantage lies in the
      significant reduction of time used for diagnosis, in addition to higher
      sensitivity.

PMID- 24901582
TI  - The subtalar joint axis palpation technique-part 1: validating a clinical
      mechanical model.
AB  - BACKGROUND: Locating the position of the subtalar joint axis can be a predictive
      clinical variable in biomechanical analysis and a valuable tool in the design of
      functional foot orthoses. Before testing Kirby's palpation technique to locate
      the subtalar joint axis in cadavers, it was important to develop and test the
      experimental methods in a mechanical model in which the exact location of the
      hinge joint can be controlled. METHODS: Four testers determined the hinge joint
      location and moved it through its range of motion, capturing the movement of the
      joint axis using a kinematic model. The joint axis location was determined and
      validated by comparing the actual hinge joint location on the mechanical model
      with the location determined by the palpation technique described by Kirby in
      1987 and the location determined by the helical joint axis method using three
      dimensional kinematic data. RESULTS: The overall angles result in mean slopes and
      intersections of 87 degrees  and 92 mm, 86 degrees  and 97 mm, 85 degrees  and 92
      mm, and 88 degrees  and 91 mm for testers 1, 2, 3, and 4, respectively. Testers 1
      and 3 were able to determine the location to 1 degrees  and 1 mm accuracy, tester
      2 to 0 degrees  and 4 mm, and tester 4 to 2 degrees  and 2 mm compared with the
      kinematic data. CONCLUSIONS: The technique of determining the points of no
      rotation as described by Kirby could be validated by using a three-dimensional
      kinematic model to determine the helical axis.

PMID- 24901583
TI  - The consistency of individual-selected versus rater-determined angle and base of
      gait.
AB  - BACKGROUND: Several studies have reported the necessity of using a standardized
      foot placement to improve reliability when performing standing foot posture
      measurements. The intent of this study was to determine whether individuals can
      reliably place their feet in the same standing position after marching in place
      or whether the standing position must be determined by a rater observing the
      angle and base of gait during walking to ensure the consistency of foot
      placement. METHODS: Twenty individuals (12 women and 8 men; mean age, 24.8 years)
      consented to participate. All of the participants were asked to march in place
      for 10 sec and then to stop in their preferred angle and base foot placement.
      Participants then walked over an 8-m walkway so that one of two raters could
      observe the participant's angle and base while walking. An angle and base of gait
      tracing was then made for each participant's foot placement. RESULTS: The two
      raters and all of the participants demonstrated high levels of reliability for
      foot placement between the two sessions. The results indicate that asking the
      participant to march in place provides a more consistent angle and base foot
      placement between two sessions compared with having a rater determine the angle
      and base of gait foot placement after observing the participant while walking.
      CONCLUSIONS: Based on these findings, we recommend using marching in place to
      position a patient in his or her angle and base foot placement when the
      measurement or visual assessment of foot posture must be performed for more than
      one clinical visit.

PMID- 24901584
TI  - Idiopathic toe-walking: have we progressed in our knowledge of the causality and
      treatment of this gait type?
AB  - BACKGROUND: Idiopathic toe-walking (ITW) is a condition commonly seen by
      podiatric physicians. Because a toe-walking gait style is also caused by or
      associated with many other medical conditions, podiatric physicians should pay
      particular attention to ensuring an accurate diagnosis. There are many reported
      treatment options available for ITW. Therefore, a literature review was conducted
      to determine what treatment options are supported by the evidence as having the
      best long-term effect on ITW gait. METHODS: After extraction of relevant
      articles, 21 manuscripts reporting treatment options for ITW gait were appraised
      against the levels of evidence. RESULTS: From these articles, there was no single
      treatment option reported as having a long-term effect on the gait of children
      with ITW. There was support in the literature for surgical interventions, serial
      casting, and the use of botulinum toxin type A. There was limited evidence that
      footwear or orthoses changed the gait pattern. CONCLUSIONS: This review updates
      the knowledge of podiatric physicians, enhances how children who present with
      this gait style can be managed, and highlights areas for future research.

PMID- 24901585
TI  - Plantar fasciitis and its relationship with hallux limitus.
AB  - BACKGROUND: We sought to determine whether patients with plantar fasciitis have
      limited dorsiflexion in the first metatarsophalangeal joint and which type of
      foot, pronated or supinated, is most frequently associated with plantar
      fasciitis. METHODS: The 100 study participants (34 men and 66 women) were divided
      into two groups: patients with plantar fasciitis and controls. The Foot Posture
      Index and dorsiflexion of the first metatarsophalangeal joint were compared
      between the two groups, and a correlation analysis was conducted to study their
      relationship. RESULTS: In the plantar fasciitis group there was a slight
      limitation of dorsiflexion of the hallux that was not present in the control
      group (P < .001). Hallux dorsiflexion and the Foot Posture Index were inversely
      correlated (Spearman correlation coefficient, -0.441; P < .01). CONCLUSIONS:
      Participants with plantar fasciitis presented less hallux dorsiflexion than those
      in the control group, and their most common foot type was the pronated foot.

PMID- 24901586
TI  - "Step up for foot care": addressing podiatric care needs in a sample homeless
      population.
AB  - BACKGROUND: Studies have shown that lower-extremity problems in the homeless
      population have significant public health and economic implications. A combined
      community service and research project was performed to identify and address the
      foot and ankle care needs in a sample homeless population in San Francisco,
      California. METHODS: A 37-question survey regarding general demographic
      characteristics, foot hygiene practices, associated risk factors, and self
      reported lower-extremity pathologic conditions was completed by 299 homeless
      individuals who met the inclusion criteria. The service project included
      education on proper foot care and the distribution of footwear. RESULTS: The
      participants demonstrated mostly good efforts regarding foot hygiene but had high
      risk factors, including smoking, alcohol use, and extended hours on their feet.
      More than half of the homeless individuals surveyed experienced foot pain.
      Approximately one in five had edema and neuropathic symptoms. The most commonly
      reported foot problems were dermatologic, but these conditions could pose serious
      sequelae in the setting of risk factors. The community service project was well
      received by the homeless community. CONCLUSIONS: This study demonstrates lack of
      resources and high-risk factors for lower-extremity complications in the homeless
      individuals studied. It is important in the realm of public health to keep lower
      extremity health in mind because it plays an important role in preventing the
      spread of infection and lowering the social economic burden.

PMID- 24901587
TI  - Placebo cure rates in the treatment of onychomycosis.
AB  - Placebo cure rates vary among randomized clinical trials for onychomycosis, but
      the factors influencing these cure rates have not been systematically
      investigated. The PubMed database and reference sections of relevant publications
      were searched for randomized controlled trials of dermatophyte toenail
      onychomycosis that included a placebo control and that assessed cure rates. From
      21 studies, the pooled mean +/- SD placebo cure rates regarding mycological,
      clinical, and complete cure were 8.7% +/- 3.7%, 3.4% +/- 2.2%, and 1.2% +/- 1.4%,
      respectively. There was no statistically significant difference between oral and
      topical treatments. None of the cure rates significantly correlated with any of
      the participant or study design characteristics analyzed. Placebo cure rates in
      randomized controlled trials of toenail onychomycosis are relatively low and are
      independent of the study characteristics. 

PMID- 24901588
TI  - Perioperative posterior heel pain caused by multiple etiologies including a
      neuroma in continuity of the posterior branch of the sural nerve: a case report.
AB  - Posterior heel pain after a prior Haglund's deformity surgical correction can be
      resultant to multiple etiologies: osseous, tendinous, and neural. In this case
      report, all three potential etiologies were found to be contributing to the
      postoperative status of the patient. This case report illustrates identification
      and treatment of a neuroma in continuity of the posterior branch of the sural
      nerve with preservation of the sural nerve itself via microdissection, which we
      believe has not been described previously in the literature. 

PMID- 24901590
TI  - Incidental pedal manifestation of primary bone lymphoma: a case report.
AB  - Primary lymphoma of bone (PLB) is an uncommon entity and is extremely rare in the
      foot and ankle. In this case, PLB was identified from the bone specimen after a
      bunionectomy of the first and fifth metatarsals. The diagnosis was confirmed with
      pathologic analysis, genetic karyotyping, positron emission and computed
      tomography scans, and fluorescence in situ hybridization (FISH). We felt that
      reporting this case was essential due to the rarity of its pedal occurrence and
      the lack of preoperative signs or symptoms. 

PMID- 24901589
TI  - A new snowboard injury caused by "FLOW" bindings: a complete deltoid ligament and
      anterior talofibular ankle ligament rupture.
AB  - We present a case of a snowboard injury that caused a combination of a complete
      deltoid and anterior talofibular ligament rupture, without bony or syndesmotic
      injury. Initial surgical repair for both ligaments was performed. We describe the
      etiology of this injury to demonstrate the cause and existence of medial and
      lateral ankle ligament rupture without osseous and syndesmotic involvement and to
      create awareness of these types of injuries. 

PMID- 24901591
TI  - Malignant melanoma presenting as a nonhealing heel ulceration.
AB  - Malignant melanoma is responsible for more than three-fourths of skin cancer
      deaths in the United States. Melanomas presenting on acral surfaces are
      frequently misdiagnosed initially, leading to progression of disease and worse
      prognosis. This case is presented to reinforce the significance of careful
      physical examination and early biopsy of atypical ulcerations of the foot. 

PMID- 24901593
TI  - Subungual schwannoma with clinical, sonographic, and histologic correlation.
AB  - We show an unusual presentation of a schwannoma that was located in the ungual
      bed of the left great toe. The clinical, color Doppler ultrasound imaging, and
      histologic findings are shown to illustrate the case. This type of neurogenic
      tumor and the ultrasound presurgical imaging support should be considered when
      dealing with subungual tumors of the foot. 

PMID- 24901592
TI  - Acute rupture of the tibialis posterior tendon without fracture: a case report.
AB  - The acute rupture of the tibialis posterior (TP) tendon, compared to an acute
      rupture of the Achilles tendon, is a quite uncommon disease to be diagnosed in
      the emergency department setting. In most cases symptoms related to a TP
      dysfunction, like weakness, pain along the course of the tendon, swelling in the
      region of the medial malleolus, and the partial or complete loss of the medial
      arch with a flatfoot deformity precede the complete rupture of the tendon. In
      this case report, we describe an acute rupture of the TP tendon following a
      pronation-external rotation injury of the ankle with no association of a medial
      malleolus fracture and with no history of a prior flatfoot deformity or symptoms.

PMID- 24901594
TI  - Doctors of podiatric medicine-on a pathway to becoming fully licensed physicians
      and surgeons? An evidence-based analysis.
AB  - Since the 1970s, the profession of podiatric medicine has undergone major changes
      in the dimensions of its practice as well as its education and training. Herein,
      I describe how podiatric medicine has evolved to become a profession of
      independent practitioners who now provide patients with comprehensive medical and
      surgical care affecting the foot and ankle in community practice, academic health
      centers, and hospital operating rooms. Preparation for the profession virtually
      mirrors the education and training of the MD and DO, including a 4-year
      postbaccalaureate curriculum with a preclinical curriculum that matches that of
      Liaison Committee on Medical Education-accredited medical schools and most of the
      clinical curriculum of undergraduate medical education. Completion of the degree
      of doctor of podiatric medicine prepares graduates to enter hospital-based
      graduate medical education programs, now 3 years in duration. A description is
      provided of the current podiatric medical practitioner now prepared at a level
      that is virtually equal to that of medical and surgical specialists who hold an
      unrestricted medical license. 

PMID- 24901595
TI  - Partial or total calcanectomy as an alternative to below-the-knee amputation for
      limb salvage.

PMID- 24901596
TI  - Author's response.

PMID- 24901597
TI  - Acceptance Address, APMA House of Delegates, Washington, DC, March 16, 2014.

PMID- 24901602
TI  - Pure and Zn-doped Pt clusters go flat and upright on MgO(100).
AB  - Pure and doped sub-nanoclusters can exhibit superb catalytic activity, which,
      however, strongly depends on their size, shape, composition, and the nature of
      the support. This work is about surface-deposited sub-nano Pt-based clusters,
      which are promising catalysts for the reactions of dehydrogenation. Using density
      functional theory and ab initio calculations, and an ab initio genetic algorithm
      for finding the global minima of clusters, we found a peculiar effect that Pt5
      and Pt4Zn clusters exhibit upon deposition on MgO(100). Both of them change
      shapes from the gas phase 3-D form to a planar form, and they stand upright on
      the support. Several reasons are responsible for this behaviour. In part,
      clusters go flat due to the electron transfer from the support. Indeed, the
      anionic Pt5(-) and Pt4Zn(-) species are flat also in the gas phase. Charging
      induces the second-order Jahn-Teller effect (or partial covalency) facilitated by
      the recruitment of the higher-energy 6p atomic orbitals on Pt into the valence
      manifold, and that is the reason for the planarization of the anions. Secondly,
      clusters maximize interactions with the surface O atoms (resulting in further
      favouring of 2-D structures over 3-D), and avoid contacts with surface Mg atoms
      (resulting in upright morphologies). 

PMID- 24901603
TI  - The role of gender and sexual experience in predicting adolescent condom use
      intentions using the theory of planned behaviour.
AB  - OBJECTIVES: To examine how the prediction of condom-related cognitions,
      intentions, and behaviour amongst adolescents may differ according to gender and
      sexual experience within a theory of planned behaviour (TPB) framework. METHODS:
      Adolescents (N = 306) completed questionnaires about sexual experience, condom
      use, TPB variables, perceived risk, and safe sex knowledge. RESULTS: Significant
      differences in TPB variables, perceived risk, and knowledge were found; males and
      sexually experienced participants were generally less positive about condom use.
      Twenty percent of the variance in attitudes was accounted for by four variables;
      specifically, female gender, no previous sexual experience, better safe sex
      knowledge, and greater risk perceptions were associated with more positive
      attitudes. The prediction of intentions separately amongst sexually experienced
      (R(2) = 0.468) and inexperienced (R(2) = 0.436) participants revealed that, for
      the former group, attitudes and subjective norms were the most important
      considerations. In contrast, among the inexperienced participants, attitudes and
      the gender-by-perceived risk interaction term represented significant influences.
      CONCLUSIONS: The results suggest that interventions designed to improve
      adolescents' intentions to use condoms and rates of actual condom use should
      consider differences in gender and sexual experience.

PMID- 24901604
TI  - Reciprocal actions of microRNA-9 and TLX in the proliferation and differentiation
      of retinal progenitor cells.
AB  - Recent research has demonstrated critical roles of a number of microRNAs (miRNAs)
      in stem cell proliferation and differentiation. miRNA-9 (miR-9) is a brain
      enriched miRNA. Whether miR-9 has a role in retinal progenitor cell (RPC)
      proliferation and differentiation remains unknown. In this study, we show that
      miR-9 plays an important role in RPC fate determination. The expression of miR-9
      was inversely correlated with that of the nuclear receptor TLX, which is an
      essential regulator of neural stem cell self-renewal. Overexpression of miR-9
      downregulated the TLX levels in RPCs, leading to reduced RPC proliferation and
      increased neuronal and glial differentiation, and the effect of miR-9
      overexpression on RPC proliferation and differentiation was inhibited by the TLX
      overexpression; knockdown of miR-9 resulted in increased TLX expression as well
      as enhanced proliferation of RPCs. Furthermore, inhibition of endogenous TLX by
      small interfering RNA suppressed RPC proliferation and promoted RPCs to
      differentiate into retinal neuronal and glial cells. These results suggest that
      miR-9 and TLX form a feedback regulatory loop to coordinate the proliferation and
      differentiation of retinal progenitors. 

PMID- 24901605
TI  - Noninvasive characterization of the healthy human manubrium using diffuse optical
      spectroscopies.
AB  - The abnormal, uncontrolled production of blood cells in the bone marrow causes
      hematological malignancies which are common and tend to have a poor prognosis.
      These types of cancers may alter the hemodynamics of bone marrow. Therefore,
      noninvasive methods that measure the hemodynamics in the bone marrow have a
      potential impact on the earlier diagnosis, more accurate prognosis, and in
      treatment monitoring. In adults, the manubrium is one of the few sites of bone
      marrow that is rich in hematopoietic tissue and is also relatively superficial
      and accessible. To this end we have combined time resolved spectroscopy and
      diffuse correlation spectroscopy to evaluate the feasibility of the noninvasive
      measurement of the hemodynamics properties of the healthy manubrium in 32
      subjects. The distribution of the optical properties (absorption and scattering)
      and physiological properties (hemoglobin concentration, oxygen saturation and
      blood flow index) of this tissue are presented as the first step toward
      investigating its pathology. 

PMID- 24901606
TI  - Arterial blood pressure and neurologic outcome after resuscitation from cardiac
      arrest*.
AB  - OBJECTIVES: Guidelines for post-cardiac arrest care recommend blood pressure
      optimization as one component of neuroprotection. Although some retrospective
      clinical studies suggest that postresuscitation hypotension may be harmful, and
      laboratory studies suggest that a postresuscitation hypertensive surge may be
      protective, empirical data are few. In this study, we prospectively measured
      blood pressure over time during the postresuscitation period and tested its
      association with neurologic outcome. DESIGN: Single center, prospective
      observational study from 2009 to 2012. PATIENTS: Inclusion criteria were age 18
      years old or older, prearrest independent functional status, resuscitation from
      cardiac arrest, and comatose immediately after resuscitation. MEASUREMENTS AND
      MAIN RESULTS: Our research protocol measured blood pressure noninvasively every
      15 minutes for the first 6 hours after resuscitation. We calculated the 0- to 6
      hour time-weighted average mean arterial pressure and used multivariable logistic
      regression to test the association between increasing time-weighted average mean
      arterial pressures and good neurologic outcome, defined as Cerebral Performance
      Category 1 or 2 at hospital discharge. Among 151 patients, 44 (29%) experienced
      good neurologic outcome. The association between blood pressure and outcome
      appears to have a threshold effect at time-weighted average mean arterial
      pressure value of 70 mm Hg. This threshold (mean arterial pressure > 70 mm Hg)
      had the strongest association with good neurologic outcome (odds ratio, 4.11; 95%
      CI, 1.34-12.66; p = 0.014). A sustained intrinsic hypertensive surge was
      relatively uncommon and was not associated with neurologic outcome. CONCLUSIONS:
      We found that time-weighted average mean arterial pressure was associated with
      good neurologic outcome at a threshold of mean arterial pressure greater than 70
      mm Hg.

PMID- 24901607
TI  - Molecular detection of Bartonella spp. in deer ked pupae, adult keds and moose
      blood in Finland.
AB  - The deer ked (Lipoptena cervi) is a haematophagous ectoparasite of cervids that
      harbours haemotrophic Bartonella. A prerequisite for the vector competence of the
      deer ked is the vertical transmission of the pathogen from the mother to its
      progeny and transstadial transmission from pupa to winged adult. We screened 1154
      pupae and 59 pools of winged adult deer keds from different areas in Finland for
      Bartonella DNA using PCR. Altogether 13 pupa samples and one winged adult deer
      ked were positive for the presence of Bartonella DNA. The amplified sequences
      were closely related to either B. schoenbuchensis or B. bovis. The same lineages
      were identified in eight blood samples collected from free-ranging moose. This is
      the first demonstration of Bartonella spp. DNA in a winged adult deer ked and,
      thus, evidence for potential transstadial transmission of Bartonella spp. in the
      species.

PMID- 24901609
TI  - A new class of organic photovoltaic materials: poly(rod-coil) polymers having
      alternative conjugated and non-conjugated segments.
AB  - A new class of organic photovoltaic materials, poly(rod-coil) polymers composed
      of alternatively definite conjugated and non-conjugated segments, have been
      proposed. The first five examples based on polyurethane chemistry showed
      photovoltaic performance surpassing the reference compound, but less dependent on
      their molecular weight. 

PMID- 24901610
TI  - Evaluation of the causes of inundation in a repeatedly flooded zone in the city
      of Cheongju, Korea, using a 1D/2D model.
AB  - Currently, unprecedented levels of damage arising from major weather events have
      been experienced in a number of major cities worldwide. Furthermore, the
      frequency and the scale of these disasters appear to be increasing and this is
      viewed by some as tangible proof of climate change. In the urbanized areas sewer
      overflows and resulting inundation are attributed to the conversion of previous
      surfaces into impervious surfaces, resulting in increased volumes of runoff which
      exceed the capacity of sewer systems and in particular combined sewer systems. In
      this study, the characteristics of sewer overflows and inundation have been
      analyzed in a repeatedly flooded zone in the city of Cheongju in Korea. This
      included an assessment of inundation in a 50-year storm event with total rainfall
      of 165 mm. A detailed XP-SWMM 2D model was assembled and run to simulate the
      interaction of the sewage system overflows and surface inundation to determine if
      inundation is due to hydraulic capacity limitations in the sewers or limitations
      in surface inlet capacities or a combination of both. Calibration was undertaken
      using observation at three locations (PT #1, PT #2, PT #3) within the study area.
      In the case of the subsurface flow calibration, R(2) value of 0.91 and 0.78
      respectively were achieved at PT #1 and PT #2. Extremely good agreement between
      observed and predicted surface flow depths was achieved also at PT #1 and PT #2.
      However, at PT #3 the predicted flow depth was 4 cm lower than the observed
      depth, which was attributed to the impact of buildings on the local flow
      distribution. Areas subject to flooding were classified as either Type A (due to
      insufficient hydraulic capacity of a sewer), Type B (which is an area without
      flooding notwithstanding insufficient hydraulic capacity of a sewer) or Type C
      (due to inlet limitations, i.e. there is hydraulic capacity in a sewer which is
      not utilized). In the total flooded zone, 24% was classified as Type A (10.2 ha)
      and 25% was classified as Type C (2.61 ha). It was concluded that greater
      attention should be paid to the area classified as Type B, which covers 50.5%
      (5.15 ha) of the total flooded zone.

PMID- 24901611
TI  - Influence of anatase and rutile phase in TiO2 upon the photocatalytic degradation
      of methylene blue under solar irradiation in presence of activated carbon.
AB  - The influence of activated carbon (AC) on the photocatalytic activity of
      different crystalline TiO2 phases was verified in the photocatalytic degradation
      of methylene blue under UV and solar irradiation. The results showed a volcano
      trend with a maximum photoactivity for the crystalline phase ratio of
      anatase:rutile equal to 80:20 both under UV or solar irradiation. By contrast, in
      presence of AC the photocatalytic activity of the binary materials of TiO2/AC
      followed an exponential trend, increasing as a function of the increase in
      anatase proportion in the TiO2 framework. The increase in the photoactivity of
      the binary material TiO2/AC relative to neat TiO2 was up to 22 and about 17 times
      higher under UV and visible irradiation, respectively. The present results
      suggest that AC interacts more efficiently with anatase phase than with rutile
      phase. 

PMID- 24901612
TI  - Temporal and spatial variation of water level in urbanizing plain river network
      region.
AB  - As one of the most developed regions in China, the plain of East China is
      undergoing gradually increased flooding under the obvious urbanization process.
      This paper mainly analyses the trend of water level time series in the region
      during the past decades, and assesses the temporal and spatial variation of water
      level and indicators of hydrological alteration. The results show that there is a
      trend of increasing water level. Bigger slope and higher significant level can be
      observed in monthly minimum than in monthly maximum water level, in peri-urban
      than in urban areas. Meanwhile, it is observed that the mean monthly minimum and
      maximum water level increased in both urban and peri-urban regions, while
      decreased coefficients of variation (Cv) in urban and increased Cv in peri-urban
      regions were calculated. Most indicators of hydrologic alteration in urban
      stations are concentrated to the range of variability approach target, while most
      indicators are discrete in peri-urban stations. And the degree of hydrologic
      alteration is higher in peri-urban than in urban regions. 

PMID- 24901613
TI  - Thermophilic two-phase anaerobic digestion of source-sorted organic fraction of
      municipal solid waste for bio-hythane production: effect of recirculation sludge
      on process stability and microbiology over a long-term pilot-scale experience.
AB  - A two-stage thermophilic anaerobic digestion process for the concurrent
      production of hydrogen and methane through the treatment of the source-sorted
      organic fraction of municipal solid waste was carried out over a long-term pilot
      scale experience. Two continuously stirred tank reactors were operated for about
      1 year. The results showed that stable production of bio-hythane without inoculum
      treatment could be obtained. The pH of the dark fermentation reactor was
      maintained in the optimal range for hydrogen-producing bacteria activity through
      sludge recirculation from a methanogenic reactor. An average specific bio-hythane
      production of 0.65 m(3) per kg of volatile solids fed was achieved when the
      recirculation flow was controlled through an evaporation unit in order to avoid
      inhibition problems for both microbial communities. Microbial analysis indicated
      that dominant bacterial species in the dark fermentation reactor are related to
      the Lactobacillus family, while the population of the methanogenic reactor was
      mainly composed of Defluviitoga tunisiensis. The archaeal community of the
      methanogenic reactor shifted, moving from Methanothermobacter-like to
      Methanobacteriales and Methanosarcinales, the latter found also in the dark
      fermentation reactor when a considerable methane production was detected. 

PMID- 24901614
TI  - Automatic control of pollutant on a shallow river using surface water systems:
      application to the Ebro River.
AB  - In this paper, the problem of automatic control of pollutant on a shallow river
      using surface water systems is addressed using a benchmark test case based in the
      Ebro River. The Ebro River presents flooding episodes in the city of Zaragoza in
      Spring when snow melts in the Pyrenees. To avoid flooding and high pollutant
      levels in living areas, some lands outside the city are prepared to be flooded.
      Going one step further, this paper is focused on the pollutant level control at a
      certain point downstream of the river under flooding episodes, and several
      control strategies for that purpose are presented and tested. 

PMID- 24901615
TI  - Removal of pharmaceuticals and personal care products in a membrane bioreactor
      wastewater treatment plant.
AB  - Ninety-nine pharmaceuticals and personal care products (PPCPs) were analyzed in
      influent, final effluent, and biosolids samples from a wastewater treatment plant
      employing a membrane bioreactor (MBR). High concentrations in influent were found
      for acetaminophen, caffeine, metformin, 2-hydroxy-ibuprofen, paraxanthine,
      ibuprofen, and naproxen (10(4)-10(5) ng/L). Final effluents contained
      clarithromycin, metformin, atenolol, carbamazepine, and trimethoprim (>500 ng/L)
      at the highest concentrations, while triclosan, ciprofloxacin, norfloxacin,
      triclocarban, metformin, caffeine, ofloxacin, and paraxanthine were found at high
      concentrations in biosolids (>10(3) ng/g dry weight). PPCP removals varied from 
      34% to >99% and 23 PPCPs had >=90% removal. Of the studied PPCPs, 26 compounds
      have been rarely or never studied in previous membrane bioreactor (MBR)
      investigations. The removal pathway showed that acetaminophen, 2-hydroxy
      ibuprofen, naproxen, ibuprofen, codeine, metformin, enalapril, atorvastatin,
      caffeine, paraxanthine, and cotinine exhibited high degradation/transformation.
      PPCPs showing strong sorption to solids included triclocarban, triclosan,
      miconazole, tetracycline, 4-epitetracycline, norfloxacin, ciprofloxacin,
      doxycycline, paroxetine, and ofloxacin. Trimethoprim, oxycodone, clarithromycin,
      thiabendazole, hydrochlorothiazide, erythromycin-H2O, carbamazepine, meprobamate,
      and propranolol were not removed during treatment, and clarithromycin was even
      formed during treatment. This investigation extended our understanding of the
      occurrence and fate of PPCPs in an MBR process through the analysis of the
      largest number of compounds in an MBR study to date. 

PMID- 24901616
TI  - Kinetic studies of Cd (II) and Pb (II) ions biosorption from aqueous media using
      untreated and chemically treated biosorbents.
AB  - Untreated and chemically treated Albizia coriaria, Erythrina abyssinica and Musa
      spp. were studied in batch for uptake of Cd(2+) and Pb(2+) ions at pH 2.0-9.0 and
      agitation time of 30-390 min. Optimum biosorption conditions were pH 4 for Pb(2+)
      ions and pH 5 for Cd(2+) ions, contact time was 3.5 hours at 24 +/- 1  degrees C
      for 10 mg/L biosorbent dosage and initial metal ions concentration of 20 mg/L.
      Chemical treatment had a 10-17% biosorption efficiency enhancement for Cd(2+)
      ions and a 1.6-2.3% reduction effect for Pb(2+) ions. The sorption capacities for
      Cd(2+) and Pb(2+) ions for treated biosorbents were 1.760-1.738 mg g(-1) compared
      to 1.415-1.539 mg g(-1) for untreated materials. The pseudo second-order model
      suitably fitted the Cd(2+) and Pb(2+) ions biosorption data with regression
      coefficients (R(2)) of 0.9784-0.9999. Fitting of the Ho model to the experimental
      data showed that the biosorption mechanism for both metal ions studied was mainly
      a chemisorption process. Therefore, treated A. coriaria, E. abyssinica and Musa
      spp. were potential biosorbents for remediation of Cd(2+) ions and the untreated
      materials suitable for removing Pb(2+) ions from contaminated aqueous media. 

PMID- 24901617
TI  - Use of flocculants for increasing permeate flux in anaerobic membrane
      bioreactors.
AB  - Biomass retention, required for high rate anaerobic wastewater treatment, can be
      accomplished coupling an anaerobic bioreactor with membrane filtration. However,
      low flux seems to be a common factor when operating anaerobic membrane
      bioreactors (AnMBRs). Modification of biomass properties may represent a strategy
      for improving membrane flux. The addition of flocculants was tested as a tool for
      flux increase. Six different products were tested in dead-end filtration
      experiments. Based on the results, two products were selected for cross-flow
      tests. The one presenting better performance (Nalco MPE50) was tested in a
      laboratory-scale continuous AnMBR. Results show that the flocculant was able to
      substantially increase flux. Indeed, the flux-increasing effect was observed for
      several weeks after flocculant addition. Therefore, the use of flocculants seems
      to be an interesting tool to cope with temporary increases in required flux. 

PMID- 24901618
TI  - Decision support for ecological river rehabilitation using fish habitat database.
AB  - After the recent success of several river rehabilitation projects including the
      Cheong-gye river case, a large number of local governments have been promoting
      their own projects in Korea. Most of the projects are aimed at securing the
      soundness of aquatic ecosystems according to the guidelines presented by the
      Korea Ministry of Environment. However, there is no clear guidance for the
      management goals of water quality and quantity. In this study, we have made an
      attempt to construct a habitat database (DB) for each domestic freshwater fish
      species. The fish population, and physical and physicochemical properties of the
      habitat of 70 domestic freshwater fish species were investigated using field
      monitoring data. After the statistical processing, the inhabitable range and
      optimal range of each species were suggested. Furthermore, based on the DB, a
      decision support system for ecological river restoration and rehabilitation has
      been developed, and applied for field tests. It became clear that the decision
      support procedure based on the fish habitat DB is useful in the planning stage of
      river rehabilitation projects to select the flagship fish, to decide the
      restoration goals considering their appropriate habitat and to suggest the
      optimum quantitative combination of each available water resource. 

PMID- 24901619
TI  - Performance of aerobic granular sludge at variable circulation rate in anaerobic
      aerobic conditions.
AB  - Aerobic granular sludge (AGS) has been applied to treat a broad range of
      industrial and municipal wastewater. AGS can be developed in a sequencing batch
      reactor (SBR) with alternating anaerobic-aerobic conditions. To provide anaerobic
      conditions, the mixed liquor is allowed to circulate in the reactor without air
      supply. The circulation flow rate of mixed liquor in anaerobic condition is the
      most important parameter of operation in the anaerobic-AGS processes. Therefore,
      this study investigates the effect of circulation rate on the performance of the
      SBR with AGS. Two identical reactors namely R1 and R2 were operated using
      fermented soy sauce wastewater at circulation rate of 14.4 and 36.0 l/h,
      respectively. During the anaerobic conditions, the wastewater was pumped out from
      the upper part of the reactor and circulated back into the bottom of the reactor
      for 230 min. A compact and dense AGS was observed in both reactors with a similar
      diameter of 2.0 mm in average, although different circulation rates were adopted.
      The best reactor performance was achieved in R2 with chemical oxygen demand
      removal rate of 89%, 90% total phosphorus removal, 79% ammonia removal, 10.1 g/l
      of mixed liquor suspended solids and a sludge volume index of 25 ml/g. 

PMID- 24901620
TI  - Development of a system for treatment of coconut industry wastewater using
      electrochemical processes followed by Fenton reaction.
AB  - The coconut processing industry generates a significant amount of liquid waste.
      New technologies targeting the treatment of industrial effluents have emerged,
      including advanced oxidation processes, the Fenton reaction, and electrochemical
      processes, which produce strong oxidizing species to remove organic matter. In
      this study we combined the Fenton reaction and electrochemical process to treat
      wastewater generated by the coconut industry. We prepared a synthetic wastewater
      consisting of a mixture of coconut milk and water and assessed how the Fenton
      reagents' concentration, the cathode material, the current density, and the
      implementation of associated technologies affect its treatment. Electrochemical
      treatment followed by the Fenton reaction diminished turbidity and chemical
      oxygen demand (COD) by 85 and 95%, respectively. The Fenton reaction followed by
      the electrochemical process reduced turbidity and COD by 93 and 85%,
      respectively. Therefore, a combination of the Fenton and electrochemical
      technologies can effectively treat the effluent from the coconut processing
      industry. 

PMID- 24901621
TI  - Sorption studies of Cr(VI) from aqueous solution using bio-char as an adsorbent.
AB  - The characteristics of sorption of hexavalent chromium (Cr(VI)) onto bio-char
      derived from wood chips (spruce, pine, and fir) were evaluated as a function of
      pH, initial Cr(VI) concentration and bio-char dosage using synthetic wastewater
      in batch tests. The initial Cr(VI) concentrations were varied between 10 and 500
      mg/L to investigate equilibrium, kinetics, and isotherms of the sorption process.
      About 100% of Cr(VI) was removed at pH 2 with initial Cr(VI) concentration of 10
      mg/L using 4 g of bio-char after 5 hours of sorption reaction. The maximum
      sorption capacity of the bio-char was 1.717 mg/g for an initial Cr(VI)
      concentration of 500 mg/L after 5 hours. The sorption kinetics of total Cr onto
      bio-char followed the second-order kinetic model. The Langmuir isotherm model
      provided the best fit for total Cr sorption onto bio-char. The bio-char used is a
      co-product of a down draft gasifier that uses the derived syngas to produce
      electricity. Bio-char as a low cost adsorbent demonstrated promising results for
      removal of Cr(VI) from aqueous solution. The findings of this study would be
      useful in designing a filtration unit with bio-char in a full-scale water and
      wastewater treatment plant for the Cr(VI) removal from contaminated waters. 

PMID- 24901622
TI  - Characterization of air plasma-activated carbon nanotube electrodes for the
      removal of lead ion.
AB  - Carbon nanotube electrodes were prepared by pressing a mixture of carbon
      nanotubes and polytetrafluoroethylene (which acted as a binder) on a stainless
      steel net collector, and the electrodes were subsequently activated in our self
      designed plasma apparatus, using air plasma. The morphology and surface
      functional groups of the electrodes were characterized using scanning electron
      microscopy and Fourier transform infrared spectroscopy, respectively. The results
      showed that the electrodes activated by air plasma possessed a rougher surface
      and more oxygen-containing groups than the raw electrodes, properties that were
      beneficial for their electrosorption performance. After 5 min of air plasma
      activation, the lead ion electrosorption capacity of the activated electrodes
      (measured at 450 mV) increased to 3.40 mg/g, which was 73% higher than the
      capacity of the non-activated, raw electrode, and 5.76 times the adsorption
      capacity of the raw electrode at 0 mV. The results of this study indicate that
      air plasma activation can be used to effectively enhance the electrosorption
      capacity of carbon nanotube electrodes. 

PMID- 24901623
TI  - Kinetics of the atrazine degradation process using H2O2-UVC.
AB  - This work is concerned with the intrinsic reaction kinetic of the degradation of
      atrazine (ATZ) using H2O2-UVC. Experimental runs were carried out in annular
      photoreactor. The initial concentration of ATZ was 2.2 * 10(-2) mol m(-3) while
      the H2O2-ATZ molar ratio range was 0-578 mol H2O2 mol(-1) ATZ. The ATZ molecules
      are decomposed by means of free-radical attack (95.2%) and direct photolysis
      (4.8%). There is an optimal H2O2/ATZ molar ratio (ROP = 347 H2O2 mol(-1) ATZ)
      which maximizes the initial degradation rate and conversion at 300 s at 83% and
      77%, respectively. The process is economically feasible as the values of the
      energy requirement, energy and H2O2 costs at ROP are 0.14 KWh m(-3) order(-1),
      US$0.02 kWh(-1) m(-3) and US$1.0 m(-3), respectively. The kinetic model proposed
      is based on Lea's reaction scheme for the H2O2 direct photolysis, the hypothesis
      that unknown ATZ sub-products that absorb UVC radiation are generated, and the
      local volumetric rate of photon absorption. The radiation transport equation was
      solved and the linear spherical source emission model was used to represent the
      lamp emission. Intrinsic reaction kinetic parameters were estimated and the model
      was validated. The model predicted the data in a range of 90 to 98%. 

PMID- 24901624
TI  - Evaluation of the extracellular polymeric substances by confocal laser scanning
      microscopy in conventional activated sludge and advanced membrane bioreactors
      treating hospital wastewater.
AB  - Confocal laser scanning microscopy (CLSM) combined with fluorescent viability
      indicators, was used in this study to investigate the impact of hospital
      wastewaters on floc structure and composition. In this work, three pilot-scale
      projects, two membrane bioreactors (MBRs) with a submerged or external membrane
      bioreactor and a conventional activated sludge, were installed and operated for
      65 days. They were fed with an influent sampled directly from the hospital
      drainage system, which contained micropollutant concentrations ranging from ng/L
      to mg/L. Samples of flocs were observed using CLSM to characterize the
      extracellular polymeric substances (EPS) stained with concanavalin A-tetra
      methylrhodamine and fluorescein isothiocyanate solution and combined with a
      fluorescent viability indicator (Baclight((r)) Bacterial Viability Kit, Molecular
      Probes), allowing visualization of isolated stained cells in the three
      dimensional structure of flocs (damaged or not). The results of CLSM of the
      sludge composition were compared with classical biochemical analysis of EPS made
      through a thermal extraction method. The results showed a good relation between
      these analyses and the statistical treatment of microscopic pictures. 

PMID- 24901625
TI  - The influence of temperature and salt on metal and sediment removal in stormwater
      biofilters.
AB  - Stormwater biofilters are used to treat stormwater runoff. In countries with cold
      winter climates, biofilters are subject to low temperatures which, in some cases,
      are combined with potentially high salt concentrations from road de-icing,
      potentially affecting the biofilter's performance. Since stormwater biofilters
      have been developed without consideration of their critical winter use, a
      laboratory study was carried out to evaluate the performance of stormwater
      biofilters subjected to low and high temperatures, with and without salt. Both
      factors and their interaction had a significant effect on outflow concentrations
      and removal percentages. Salt had a negative impact on outflow concentrations,
      causing lower removal percentages for (especially dissolved) metals, this impact
      being most pronounced for Cu and Pb. The unrealistic combination of salt with
      high temperature seemed to further amplify the negative impacts of salt despite
      the fact that temperature alone did not cause significant differences in outflow
      concentrations and removal percentages. Still, biofilters showed the ability to
      treat stormwater efficiently under the simulated winter conditions; outflow
      concentrations for total metals as a minimum met the class 4 threshold value
      defined in the Swedish freshwater quality guidelines, while inflow concentrations
      clearly exceeded the threshold value for class 5. The relatively coarse filter
      material (which is recommended to facilitate infiltration during winter) did not
      seem to exacerbate biofilter performance. 

PMID- 24901626
TI  - Method for outlier detection: a tool to assess the consistency between laboratory
      data and ultraviolet-visible absorbance spectra in wastewater samples.
AB  - Reliable estimations of the evolution of water quality parameters by using in
      situ technologies make it possible to follow the operation of a wastewater
      treatment plant (WWTP), as well as improving the understanding and control of the
      operation, especially in the detection of disturbances. However, ultraviolet (UV)
      Vis sensors have to be calibrated by means of a local fingerprint laboratory
      reference concentration-value data-set. The detection of outliers in these data
      sets is therefore important. This paper presents a method for detecting outliers
      in UV-Vis absorbances coupled to water quality reference laboratory
      concentrations for samples used for calibration purposes. Application to samples
      from the influent of the San Fernando WWTP (Medellin, Colombia) is shown. After
      the removal of outliers, improvements in the predictability of the influent
      concentrations using absorbance spectra were found. 

PMID- 24901627
TI  - Monitoring intracellular polyphosphate accumulation in enhanced biological
      phosphorus removal systems by quantitative image analysis.
AB  - A rapid methodology for intracellular storage polyphosphate (poly-P)
      identification and monitoring in enhanced biological phosphorus removal (EBPR)
      systems is proposed based on quantitative image analysis (QIA). In EBPR systems,
      4',6-diamidino-2-phenylindole (DAPI) is usually combined with fluorescence in
      situ hybridization to evaluate the microbial community. The proposed monitoring
      technique is based on a QIA procedure specifically developed for determining poly
      P inclusions within a biomass suspension using solely DAPI by epifluorescence
      microscopy. Due to contradictory literature regarding DAPI concentrations used
      for poly-P detection, the present work assessed the optimal DAPI concentration
      for samples acquired at the end of the EBPR aerobic stage when the accumulation
      occurred. Digital images were then acquired and processed by means of image
      processing and analysis. A correlation was found between average poly-P intensity
      values and the analytical determination. The proposed methodology can be seen as
      a promising alternative procedure for quantifying intracellular poly-P
      accumulation in a faster and less labour-intensive way. 

PMID- 24901628
TI  - Biomass properties and permeability in an immersed hollow fibre membrane
      bioreactor at high sludge concentrations.
AB  - This study aimed to investigate the influence of biomass properties and high
      mixed liquor suspended solids (MLSS) concentrations on membrane permeability in a
      pilot-scale hollow fibre membrane bioreactor treating domestic wastewater.
      Auxiliary molasses solution was added to maintain system operation at constant
      food-to-microorganisms ratio (F/M = 0.13). Various physicochemical and biological
      biomass parameters were measured throughout the trial, comprising pre-thickening,
      thickening and post-thickening periods with reference to the sludge concentration
      and with aerobic biotreatment continuing throughout. Correlations between dynamic
      changes in biomass characteristics and membrane permeability decline as well as
      permeability recovery were further assessed by statistical analyses. Results
      showed the MLSS concentration to exert the greatest influence on sustainable
      membrane permeability, with a weaker correlation with particle size distribution.
      The strong dependence of absolute recovered permeability on wet accumulated
      solids (WACS) concentration, or clogging propensity, revealed clogging to
      deleteriously affect membrane permeability decline and recovery (from mechanical
      declogging and chemical cleaning), with WACS levels increasing with increasing
      MLSS. Evidence from the study indicated clogging may permanently reduce membrane
      permeability post declogging and chemical cleaning, corroborating previously
      reported findings. 

PMID- 24901629
TI  - Performance of a half-saturated vertical flow wetland packed with volcanic gravel
      in stormwater treatment.
AB  - A half-saturated pilot-scale wetland planted with Acorus calamus was built to
      treat urban stormwater. The design comprises a sedimentation tank for
      pretreatment, and a vertical flow volcanic gravel wetland bed equipped with a
      recirculation device. Eighteen rainfall events were monitored in 2012. The
      treatment system achieved total removal efficiencies of 99.4, 81, 50, and 86% for
      suspended solids, organic matter, nitrogen and phosphorus, respectively, and 29,
      68, and 25% for copper, zinc, and lead, respectively, at a 3-day hydraulic
      residence time. In the wetland bed, the removal of ammonia, total nitrogen, and
      zinc were improved by recirculation. Plant uptake provided 18% of nitrogen
      removal and 39% of phosphorus removal. During the experimental stage, only 1.4%
      of the pore volume in substrate was reduced due to clogging, implying that the
      wetland can operate without clogging for a relatively long period. 

PMID- 24901630
TI  - Dynamic one-dimensional modeling of secondary settling tanks and system
      robustness evaluation.
AB  - One-dimensional secondary settling tank models are widely used in current
      engineering practice for design and optimization, and usually can be expressed as
      a nonlinear hyperbolic or nonlinear strongly degenerate parabolic partial
      differential equation (PDE). Reliable numerical methods are needed to produce
      approximate solutions that converge to the exact analytical solutions. In this
      study, we introduced a reliable numerical technique, the Yee-Roe-Davis (YRD)
      method as the governing PDE solver, and compared its reliability with the
      prevalent Stenstrom-Vitasovic-Takacs (SVT) method by assessing their simulation
      results at various operating conditions. The YRD method also produced a similar
      solution to the previously developed Method G and Enquist-Osher method. The YRD
      and SVT methods were also used for a time-to-failure evaluation, and the results
      show that the choice of numerical method can greatly impact the solution.
      Reliable numerical methods, such as the YRD method, are strongly recommended. 

PMID- 24901631
TI  - A modified anaerobic digestion process with chemical sludge pre-treatment and its
      modelling.
AB  - Activated Sludge Models (ASMs) assume an unbiodegradable organic particulate
      fraction in the activated sludge, which is derived from the decay of active
      microorganisms in the sludge and/or introduced from wastewater. In this study, a
      seasonal change of such activated sludge constituents in a municipal wastewater
      treatment plant was monitored for 1.5 years. The chemical oxygen demand ratio of
      the unbiodegradable particulates to the sludge showed a sinusoidal pattern
      ranging from 40 to 65% along with the change of water temperature in the plant
      that affected the decay rate. The biogas production in a laboratory-scale
      anaerobic digestion (AD) process was also affected by the unbiodegradable
      fraction in the activated sludge fed. Based on the results a chemical pre
      treatment using H2O2 was conducted on the digestate to convert the
      unbiodegradable fraction to a biodegradable one. Once the pre-treated digestate
      was returned to the digester, the methane conversion increased up to 80% which
      was about 2.4 times as much as that of the conventional AD process, whilst 96% of
      volatile solids in the activated sludge was digested. From the experiment, the
      additional route of the organic conversion processes for the inert fraction at
      the pre-treatment stage was modelled on the ASM platform with reasonable
      simulation accuracy. 

PMID- 24901632
TI  - Evaluation of the effects of nanoscale zero-valent iron (nZVI) dispersants on
      intrinsic biodegradation of trichloroethylene (TCE).
AB  - In this study, the biodegradability of nanoscale zero-valent iron (nZVI)
      dispersants and their effects on the intrinsic biodegradation of
      trichloroethylene (TCE) were evaluated. Results of a microcosm study show that
      the biodegradability of three dispersants followed the sequence of: polyvinyl
      alcohol-co-vinyl acetate-co-itaconic acid (PV3A) > polyoxyethylene (20) sorbitan
      monolaurate (Tween 20) > polyacrylic acid (PAA) under aerobic conditions, and
      PV3A > Tween 20 > PAA under anaerobic conditions. Natural biodegradation of TCE
      was observed under both aerobic and anaerobic conditions. No significant effects
      were observed on the intrinsic biodegradation of TCE under aerobic conditions
      with the presence of the dispersants. The addition of PAA seemed to have a
      slightly adverse impact on anaerobic TCE biodegradation. Higher accumulation of
      the byproducts of anaerobic TCE biodegradation was detected with the addition of
      PV3A and Tween 20. The diversity of the microbial community was enhanced under
      aerobic conditions with the presence of more biodegradable PV3A and Tween 20. The
      results of this study indicate that it is necessary to select an appropriate
      dispersant for nZVI to prevent a residual of the dispersant in the subsurface.
      Additionally, the effects of the dispersant on TCE biodegradation and the
      accumulation of TCE biodegrading byproducts should also be considered. 

PMID- 24901633
TI  - Issues concerning spectral analysis of water samples for monitoring and treatment
      of public water resources.
AB  - Experimental measurements conducted in the laboratory, involving hyperspectral
      analysis of water samples taken from public water resources, have motivated a re
      evaluation of issues concerning the potential application of this type of
      analysis for water monitoring, treatment and evaluation prior to filtration. One
      issue concerns hyperspectral monitoring of contaminants with respect to types and
      relative concentrations. This implies a need to better understand the statistical
      profiles of water contaminants in terms of spatial-temporal distributions of
      electromagnetic absorption spectra ranging from the ultraviolet to infrared,
      which are associated with specific water resources. This issue also implies the
      need to establish correlations between hyperspectral signatures and types of
      contaminants to be found within specific water resources. Another issue concerns
      the use of absorption spectra to determine changes in chemical and physical
      characteristics of contaminants after application of water treatments, in order
      to determine levels of toxicity with respect to the environment. This paper
      presents a prototype spectral analysis showing various aspects relevant to water
      monitoring and discusses the use of basic theory for the interpretation of
      spectral features associated with water contaminants, as well as discussing
      inverse analysis of hyperspectral measurements. 

PMID- 24901634
TI  - Activated carbon for the removal of pharmaceutical residues from treated
      wastewater.
AB  - Pharmaceutical residues, which pass naturally through the human body into sewage,
      are in many cases virtually unaffected by conventional wastewater treatment.
      Accumulated in the environment, however, they can significantly impact aquatic
      life. The present study indicates that many pharmaceutical residues found in
      wastewater can be removed with activated carbon in a cost-efficient system that
      delivers higher resource utilisation and security than other carbon systems. The
      experiment revealed a substantial separation of the analysed compounds,
      notwithstanding their relatively high solubility in water and dissimilar chemical
      structures. This implies that beds of activated carbon may be a competitive
      alternative to treatment with ozone. The effluent water used for the tests,
      performed over 20 months, originated from Stockholm's largest sewage treatment
      plant. Passing through a number of different filters with activated carbon
      removed 90-98% of the pharmaceutical residues from the water. This paper
      describes pilot-scale tests performed by IVL and the implications for an actual
      treatment plant that has to treat up to several thousand litres of wastewater per
      second. In addition, the advantages, disadvantages and costs of the method are
      discussed. This includes, for example, the clogging of carbon filters and the
      associated hydraulic capacity limits of the activated carbon. 

PMID- 24901635
TI  - Comparison of pressure support ventilation and T-piece in determining rapid
      shallow breathing index in spontaneous breathing trials.
AB  - BACKGROUND: The threshold values of rapid shallow breathing index (RSBI) were
      compared in pressure support ventilation (PSV) and T-piece assessments for
      spontaneous breathing trials (SBT). The ability of DeltaRSBI to also predict
      successful weaning was evaluated. METHODS: Two hundred eight patients were weaned
      from mechanical ventilation through oral intubation. They were randomly divided
      into PSV group (n = 93) and T-piece group (n = 115). The RSBI was calculated as
      f/VT at SBT of 3 and 30 minutes. Receiver operating characteristic curves of RSBI
      were also generated, cutoff values were determined and the changes in the RSBI
      were calculated. RESULTS: Of the 208 patients, 168 (80.77%) were successfully
      weaned from mechanical ventilation, 78/93 (83.9%) in the PSV group and 90/115
      (78.3%) in the T-piece group (P > 0.05). In the PSV and T-piece groups, the
      average RSBI at 30-minute SBT was 67.18 +/- 11.55 breaths per min/L and 99.11 +/-
      15.53 breaths per min/L, respectively (P < 0.01), and the average DeltaRSBI was
      69 +/- 33% and 119 +/- 35%, respectively (P < 0.01). Additionally, in the 2
      groups, an RSBI of 75 breaths per min/L (PSV) and 100 breaths per min/L (T-piece)
      yielded a diagnostic accuracy of 87% and 82% respectively. However, a DeltaRSBI
      of 90% (PSV) and 130% (T-piece) yielded a diagnostic accuracy of 82% and 77%
      respectively. CONCLUSIONS: The threshold values of RSBI, thus 75 breaths per
      min/L (PSV) and 100 breaths per min/L (T-piece), for predicting successful
      weaning were more accurate than other values. Similarly, the change in the RSBI
      could also predict such successes.

PMID- 24901637
TI  - Electroreductive coupling of optically active alpha,beta-unsaturated carbonyl
      compounds with diaryl ketones: asymmetric synthesis of 4,5,5-trisubstituted gamma
      butyrolactones.
AB  - The electroreductive coupling of optically active N-E-crotonoyl- and N
      cinnamoylimidazolidin-2-ones and oxazolidin-2-ones with diaryl ketones in the
      presence of chlorotrimethylsilane gave adducts with high diastereoselectivity.
      The adducts were readily transformed to optically active 4,5,5-trisubstituted
      gamma-butyrolactones by treatment with TBAF. 

PMID- 24901636
TI  - Structure and dynamics analysis on plexin-B1 Rho GTPase binding domain as a
      monomer and dimer.
AB  - Plexin-B1 is a single-pass transmembrane receptor. Its Rho GTPase binding domain
      (RBD) can associate with small Rho GTPases and can also self-bind to form a
      dimer. In total, more than 400 ns of NAMD molecular dynamics simulations were
      performed on RBD monomer and dimer. Different analysis methods, such as root mean
      squared fluctuation (RMSF), order parameters (S(2)), dihedral angle correlation,
      transfer entropy, principal component analysis, and dynamical network analysis,
      were carried out to characterize the motions seen in the trajectories. RMSF
      results show that after binding, the L4 loop becomes more rigid, but the L2 loop
      and a number of residues in other regions become slightly more flexible.
      Calculating order parameters (S(2)) for CH, NH, and CO bonds on both backbone and
      side chain shows that the L4 loop becomes essentially rigid after binding, but
      part of the L1 loop becomes slightly more flexible. Backbone dihedral angle cross
      correlation results show that loop regions such as the L1 loop including residues
      Q25 and G26, the L2 loop including residue R61, and the L4 loop including
      residues L89-R91, are highly correlated compared to other regions in the monomer
      form. Analysis of the correlated motions at these residues, such as Q25 and R61,
      indicate two signal pathways. Transfer entropy calculations on the RBD monomer
      and dimer forms suggest that the binding process should be driven by the L4 loop
      and C-terminal. However, after binding, the L4 loop functions as the motion
      responder. The signal pathways in RBD were predicted based on a dynamical network
      analysis method using the pathways predicted from the dihedral angle cross
      correlation calculations as input. It is found that the shortest pathways
      predicted from both inputs can overlap, but signal pathway 2 (from F90 to R61) is
      more dominant and overlaps all of the routes of pathway 1 (from F90 to P111).
      This project confirms the allosteric mechanism in signal transmission inside the
      RBD network, which was in part proposed in the previous experimental study. 

PMID- 24901638
TI  - Messages do diffuse faster than messengers: reconciling disparate estimates of
      the morphogen bicoid diffusion coefficient.
AB  - The gradient of Bicoid (Bcd) is key for the establishment of the anterior
      posterior axis in Drosophila embryos. The gradient properties are compatible with
      the SDD model in which Bcd is synthesized at the anterior pole and then diffuses
      into the embryo and is degraded with a characteristic time. Within this model,
      the Bcd diffusion coefficient is critical to set the timescale of gradient
      formation. This coefficient has been measured using two optical techniques,
      Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Correlation
      Spectroscopy (FCS), obtaining estimates in which the FCS value is an order of
      magnitude larger than the FRAP one. This discrepancy raises the following
      questions: which estimate is "correct''; what is the reason for the disparity;
      and can the SDD model explain Bcd gradient formation within the experimentally
      observed times? In this paper, we use a simple biophysical model in which Bcd
      diffuses and interacts with binding sites to show that both the FRAP and the FCS
      estimates may be correct and compatible with the observed timescale of gradient
      formation. The discrepancy arises from the fact that FCS and FRAP report on
      different effective (concentration dependent) diffusion coefficients, one of
      which describes the spreading rate of the individual Bcd molecules (the
      messengers) and the other one that of their concentration (the message). The
      latter is the one that is more relevant for the gradient establishment and is
      compatible with its formation within the experimentally observed times. 

PMID- 24901639
TI  - Structural insight into the tetramerization of an iterative ketoreductase siam
      through aromatic residues in the interfaces.
AB  - In the biosynthesis of polyketides, ketoreductases (KRs) are an important group
      of enzymes that determine the chiralities of the carbon backbones. SiaM is a
      special member of this group that can recognize substrates with different lengths
      and can be used iteratively. Here we report the crystal structure of SiaM.
      Structural analysis indicates that the overall structure resembles those of other
      KRs. However, significant disparity can be found in the conserved LDD motif that
      is replaced with IRD motif in SiaM. The isoleucine and aspartic acid residues
      take similar orientations as leucine and aspartic acid in the conserved LDD
      motif, while the arginine residue points out towards the solvent. PISA analysis
      shows that SiaM forms a tetramer. Several aromatic residues are found in the
      interfaces, which have aromatic stacking interactions with the aromatic residues
      in the neighboring protomers. Mutagenesis studies performed on the aromatic
      residues show that these sites are important for maintaining the structural
      integrity of SiaM. However, the aromatic residues contribute differently to the
      enzymatic activity. In the N-terminal interface, the aromatic residues can be
      replaced with leucine without affecting the enzymatic activity while, in the
      other interface, such mutations abolish the enzymatic activity. 

PMID- 24901640
TI  - Mining of the pyrrolamide antibiotics analogs in Streptomyces netropsis reveals
      the amidohydrolase-dependent "iterative strategy" underlying the pyrrole
      polymerization.
AB  - In biosynthesis of natural products, potential intermediates or analogs of a
      particular compound in the crude extracts are commonly overlooked in routine
      assays due to their low concentration, limited structural information, or because
      of their insignificant bio-activities. This may lead into an incomplete and even
      an incorrect biosynthetic pathway for the target molecule. Here we applied
      multiple compound mining approaches, including genome scanning and precursor ion
      scan-directed mass spectrometry, to identify potential pyrrolamide compounds in
      the fermentation culture of Streptomyces netropsis. Several novel congocidine and
      distamycin analogs were thus detected and characterized. A more reasonable route
      for the biosynthesis of pyrrolamides was proposed based on the structures of
      these newly discovered compounds, as well as the functional characterization of
      several key biosynthetic genes of pyrrolamides. Collectively, our results implied
      an unusual "iterative strategy" underlying the pyrrole polymerization in the
      biosynthesis of pyrrolamide antibiotics. 

PMID- 24901642
TI  - African programme for onchocerciasis control 1995-2015: updated health impact
      estimates based on new disability weights.

PMID- 24901643
TI  - The subfamily-specific interaction between Kv2.1 and Kv6.4 subunits is determined
      by interactions between the N- and C-termini.
AB  - The "silent" voltage-gated potassium (KvS) channel subunit Kv6.4 does not form
      electrically functional homotetramers at the plasma membrane but assembles with
      Kv2.1 subunits, generating functional Kv2.1/Kv6.4 heterotetramers. The N-terminal
      T1 domain determines the subfamily-specific assembly of Kv1-4 subunits by
      preventing interactions between subunits that belong to different subfamilies.
      For Kv6.4, yeast-two-hybrid experiments showed an interaction of the Kv6.4 N
      terminus with the Kv2.1 N-terminus, but unexpectedly also with the Kv3.1 N
      terminus. We confirmed this interaction by Fluorescence Resonance Energy Transfer
      (FRET) and co-immunoprecipitation (co-IP) using N-terminal Kv3.1 and Kv6.4
      fragments. However, full-length Kv3.1 and Kv6.4 subunits do not form
      heterotetramers at the plasma membrane. Therefore, additional interactions
      between the Kv6.4 and Kv2.1 subunits should be important in the Kv2.1/Kv6.4
      subfamily-specificity. Using FRET and co-IP approaches with N- and C-terminal
      fragments we observed that the Kv6.4 C-terminus physically interacts with the
      Kv2.1 N-terminus but not with the Kv3.1 N-terminus. The N-terminal amino acid
      sequence CDD which is conserved between Kv2 and KvS subunits appeared to be a key
      determinant since charge reversals with arginine substitutions abolished the
      interaction between the N-terminus of Kv2.1 and the C-terminus of both Kv2.1 and
      Kv6.4. In addition, the Kv6.4(CKv3.1) chimera in which the C-terminus of Kv6.4
      was replaced by the corresponding domain of Kv3.1, disrupted the assembly with
      Kv2.1. These results indicate that the subfamily-specific Kv2.1/Kv6.4
      heterotetramerization is determined by interactions between Kv2.1 and Kv6.4 that
      involve both the N- and C-termini in which the conserved N-terminal CDD sequence
      plays a key role.

PMID- 24901644
TI  - Stage-dependent expression and up-regulation of trypanothione synthetase in
      amphotericin B resistant Leishmania donovani.
AB  - Kinetoplastids differ from other organisms in their ability to conjugate
      glutathione and spermidine to form trypanothione which is involved in maintaining
      redox homeostasis and removal of toxic metabolites. It is also involved in drug
      resistance, antioxidant mechanism, and defense against cellular oxidants.
      Trypanothione synthetase (TryS) of thiol metabolic pathway is the sole enzyme
      responsible for the biosynthesis of trypanothione in Leishmania donovani. In this
      study, TryS gene of L. donovani (LdTryS) was cloned, expressed, and fusion
      protein purified with affinity column chromatography. The purified protein showed
      optimum enzymatic activity at pH 8.0-8.5. The TryS amino acids sequences
      alignment showed that all amino acids involved in catalytic and ligands binding
      of L. major are conserved in L. donovani. Subcellular localization using
      digitonin fractionation and immunoblot analysis showed that LdTryS is localized
      in the cytoplasm. Furthermore, RT-PCR coupled with immunoblot analysis showed
      that LdTryS is overexpressed in Amp B resistant and stationary phase
      promastigotes (~ 2.0-folds) than in sensitive strain and logarithmic phase,
      respectively, which suggests its involvement in Amp B resistance. Also, H2O2
      treatment upto 150 uM for 8 hrs leads to 2-fold increased expression of LdTryS
      probably to cope up with oxidative stress generated by H2O2. Therefore, this
      study demonstrates stage- and Amp B sensitivity-dependent expression of LdTryS in
      L. donovani and involvement of TryS during oxidative stress to help the parasites
      survival.

PMID- 24901645
TI  - HIF-1alpha inhibition reverses multidrug resistance in colon cancer cells via
      downregulation of MDR1/P-glycoprotein.
AB  - BACKGROUND: Multidrug resistance (MDR) is one of the major reasons chemotherapy
      based treatments fail. Hypoxia is generally associated with tumor
      chemoresistance. However, the correlation between the heterodimeric hypoxia
      inducible factor-1 (HIF-1) and the multidrug resistance (MDR1) gene/transporter P
      glycoprotein (P-gp) remains unclear. This study aims to explore the molecular
      mechanisms of reversing colon cancer MDR by focusing on the target gene HIF
      1alpha. METHODS: A chemotherapeutic sensitivity assay was used to observe the
      efficiency of MDR reversal in LoVo multicellular spheroids (MCS). The apoptotic
      level induced by different drugs was examined by flow cytometry (FCM). Binding of
      HIF-1alpha to the MDR1 gene promoter was evaluated by Chromatin
      immunoprecipitation (ChIP). The relationship between HIF-1alpha/P-gp expression
      and sensitivity to chemotherapy was analyzed. RESULTS: The sensitivity of LoVo
      MCS to all four chemotherapy drugs was decreased to varying degrees under hypoxic
      conditions. After silencing the HIF-1alpha gene, the sensitivities of LoVo MCS to
      all four chemotherapy drugs were restored. The apoptotic levels that all the
      drugs induced were all decreased to various extents in the hypoxic group. After
      silencing HIF-1alpha, the apoptosis level induced by all four chemotherapy drugs
      increased. The expression of HIF-1alpha and P-gp was significantly enhanced in
      LoVo MCS after treatment with hypoxia. Inhibiting HIF-1alpha significantly
      decreased the expression of MDR1/P-gp mRNA or protein in both the LoVo monolayers
      and LoVo MCS. The ChIP assay showed that HIF-1alpha was bound to the MDR1 gene
      promoter. Advanced colon carcinoma patients with expression of both HIF-1alpha
      and P-gp were more resistant to chemotherapy than that with non expression.
      CONCLUSIONS: HIF-1alpha inhibition reverses multidrug resistance in colon cancer
      cells via downregulation of MDR1/P-gp. The expression of HIF-1alpha and MDR1/P-gp
      can be used as a predictive marker for chemotherapy resistance in colon cancer.

PMID- 24901646
TI  - Enantioselective imidation of sulfides via enzyme-catalyzed intermolecular
      nitrogen-atom transfer.
AB  - Engineering enzymes with novel reaction modes promises to expand the applications
      of biocatalysis in chemical synthesis and will enhance our understanding of how
      enzymes acquire new functions. The insertion of nitrogen-containing functional
      groups into unactivated C-H bonds is not catalyzed by known enzymes but was
      recently demonstrated using engineered variants of cytochrome P450BM3 (CYP102A1)
      from Bacillus megaterium. Here, we extend this novel P450-catalyzed reaction to
      include intermolecular insertion of nitrogen into thioethers to form sulfimides.
      An examination of the reactivity of different P450BM3 variants toward a range of
      substrates demonstrates that electronic properties of the substrates are
      important in this novel enzyme-catalyzed reaction. Moreover, amino acid
      substitutions have a large effect on the rate and stereoselectivity of
      sulfimidation, demonstrating that the protein plays a key role in determining
      reactivity and selectivity. These results provide a stepping stone for
      engineering more complex nitrogen-atom-transfer reactions in P450 enzymes and
      developing a more comprehensive biocatalytic repertoire. 

PMID- 24901647
TI  - Resveratrol and arsenic trioxide act synergistically to kill tumor cells in vitro
      and in vivo.
AB  - BACKGROUND AND AIMS: Arsenic trioxide (As2O3), which used as an effective agent
      in the treatment of leukaemia and other solid tumors, is largely limited by its
      toxicity. QT prolongation, torsades de pointes and sudden heart death have been
      implicated in the cardiotoxicity of As2O3. The present study was designed to
      explore whether the combination of As2O3 and resveratrol could generate a more
      powerful anti-cancer effect both in vitro and in vivo. MATERIALS AND METHODS: MTT
      assay was performed to assess the proliferation of Hela, MCF-7 and NB4 cells.
      Isobolographic analysis was used to evaluate combination index values from cell
      viability data. The apoptosis and the cellular reactive oxygen species (ROS)
      level were assessed by fluorescent microscopy and flow cytometry separately in
      vitro. The effect of As2O3, alone and in combination with resveratrol on Hela
      tumor growth in an orthotopic nude mouse model was also investigated. The tumor
      volume and the immunohistochemical analysis of CD31, CD34 and VEGF were
      determined. RESULTS: Resveratrol dramatically enhanced the anti-cancer effect
      induced by As2O3 in vitro. In addition, isobolographic analysis further
      demonstrated that As2O3 and resveratrol generated a synergistic action. More
      apoptosis and ROS generation were observed in the combination treatment group.
      Similar synergistic effects were found in nude mice in vivo. The combination of
      As2O3 and resveratrol dramatically suppressed both tumor growth and angiogenesis
      in nude mice. CONCLUSIONS: Combining As2O3 with resveratrol would be a novel
      strategy to treat cancer in clinical practice.

PMID- 24901648
TI  - Identification of divergent protein domains by combining HMM-HMM comparisons and
      co-occurrence detection.
AB  - Identification of protein domains is a key step for understanding protein
      function. Hidden Markov Models (HMMs) have proved to be a powerful tool for this
      task. The Pfam database notably provides a large collection of HMMs which are
      widely used for the annotation of proteins in sequenced organisms. This is done
      via sequence/HMM comparisons. However, this approach may lack sensitivity when
      searching for domains in divergent species. Recently, methods for HMM/HMM
      comparisons have been proposed and proved to be more sensitive than sequence/HMM
      approaches in certain cases. However, these approaches are usually not used for
      protein domain discovery at a genome scale, and the benefit that could be
      expected from their utilization for this problem has not been investigated. Using
      proteins of P. falciparum and L. major as examples, we investigate the extent to
      which HMM/HMM comparisons can identify new domain occurrences not already
      identified by sequence/HMM approaches. We show that although HMM/HMM comparisons
      are much more sensitive than sequence/HMM comparisons, they are not sufficiently
      accurate to be used as a standalone complement of sequence/HMM approaches at the
      genome scale. Hence, we propose to use domain co-occurrence--the general domain
      tendency to preferentially appear along with some favorite domains in the
      proteins--to improve the accuracy of the approach. We show that the combination
      of HMM/HMM comparisons and co-occurrence domain detection boosts protein
      annotations. At an estimated False Discovery Rate of 5%, it revealed 901 and 1098
      new domains in Plasmodium and Leishmania proteins, respectively. Manual
      inspection of part of these predictions shows that it contains several domain
      families that were missing in the two organisms. All new domain occurrences have
      been integrated in the EuPathDomains database, along with the GO annotations that
      can be deduced.

PMID- 24901649
TI  - Factors affecting the accuracy of controlled attenuation parameter (CAP) in
      assessing hepatic steatosis in patients with chronic liver disease.
AB  - BACKGROUND & AIMS: Controlled attenuation parameter (CAP) can measure hepatic
      steatosis. However, factors affecting its accuracy have not been described yet.
      This study investigated predictors of discordance between liver biopsy (LB) and
      CAP. METHODS: A total of 161 consecutive patients with chronic liver disease who
      underwent LB and CAP were enrolled prospectively. Histological steatosis was
      graded as S0 (<5%), S1 (5-33%), S2 (34-66%), and S3 (>66% of hepatocytes). Cutoff
      CAP values were calculated from our cohort (250, 301, and 325 dB/m for >= S1, >=
      S2, and S3). Discordance was defined as a discrepancy of at least two steatosis
      stages between LB and CAP. RESULTS: The median age (102 males and 59 females) was
      49 years. Repartition of histological steatosis was as follows; S0 26.1% (n =
      42), S1 49.7% (n = 80), S2 20.5% (n = 33), and S3 3.7% (n = 6). In multivariate
      linear regression analysis, CAP value was independently associated with steatosis
      grade along with body mass index (BMI) and interquartile range/median of CAP
      value (IQR/MCAP) (all P<0.05). Discordance was identified in 13 (8.1%) patients.
      In multivariate analysis, histological S3 (odd ratio [OR], 9.573; 95% confidence
      interval [CI], 1.207-75.931; P = 0.033) and CAP value (OR, 1.020; 95% CI, 1.006
      1.034; P = 0.006) were significantly associated with discordance, when adjusting
      for BMI, IQR/MCAP, and necroinflammation, reflected by histological activity or
      ALT level. CONCLUSIONS: Patients with high grade steatosis or high CAP values
      have a higher risk of discordance between LB and CAP. Further studies are needed
      to improve the accuracy of CAP interpretation, especially in patients with higher
      CAP values.

PMID- 24901650
TI  - Ancient DNA analysis of 8000 B.C. near eastern farmers supports an early
      neolithic pioneer maritime colonization of Mainland Europe through Cyprus and the
      Aegean Islands.
AB  - The genetic impact associated to the Neolithic spread in Europe has been widely
      debated over the last 20 years. Within this context, ancient DNA studies have
      provided a more reliable picture by directly analyzing the protagonist
      populations at different regions in Europe. However, the lack of available data
      from the original Near Eastern farmers has limited the achieved conclusions,
      preventing the formulation of continental models of Neolithic expansion. Here we
      address this issue by presenting mitochondrial DNA data of the original Near
      Eastern Neolithic communities with the aim of providing the adequate background
      for the interpretation of Neolithic genetic data from European samples. Sixty
      three skeletons from the Pre Pottery Neolithic B (PPNB) sites of Tell Halula,
      Tell Ramad and Dja'de El Mughara dating between 8,700-6,600 cal. B.C. were
      analyzed, and 15 validated mitochondrial DNA profiles were recovered. In order to
      estimate the demographic contribution of the first farmers to both Central
      European and Western Mediterranean Neolithic cultures, haplotype and haplogroup
      diversities in the PPNB sample were compared using phylogeographic and population
      genetic analyses to available ancient DNA data from human remains belonging to
      the Linearbandkeramik-Alfoldi Vonaldiszes Keramia and Cardial/Epicardial
      cultures. We also searched for possible signatures of the original Neolithic
      expansion over the modern Near Eastern and South European genetic pools, and
      tried to infer possible routes of expansion by comparing the obtained results to
      a database of 60 modern populations from both regions. Comparisons performed
      among the 3 ancient datasets allowed us to identify K and N-derived mitochondrial
      DNA haplogroups as potential markers of the Neolithic expansion, whose genetic
      signature would have reached both the Iberian coasts and the Central European
      plain. Moreover, the observed genetic affinities between the PPNB samples and the
      modern populations of Cyprus and Crete seem to suggest that the Neolithic was
      first introduced into Europe through pioneer seafaring colonization. 

PMID- 24901651
TI  - A comparison of inflammatory, cytoprotective and injury gene expression profiles
      in kidneys from brain death and cardiac death donors.
AB  - BACKGROUND: The superior long-term survival of kidneys from living donors (LDs)
      compared with kidneys from donation-after-brain-death (DBD) and donation-after
      cardiac-death (DCD) donors is now well established. However, comparative studies
      on transcriptional changes that occur at organ retrieval and during and after
      cold ischemia (CI) are sparse. METHODS: Using a rat model, we used qRT-PCR to
      examine expression levels of inflammatory, cytoprotective, and injury genes at
      different time points after organ retrieval. Cleaved caspase-3 was used to
      evaluate early apoptosis in DCD and DBD kidneys. RESULTS: Immediately after
      retrieval, we found massive up-regulation of proinflammatory genes interleukin
      1beta, interleukin-6, tumor necrosis factor-alpha, monocyte chemotactic protein
      1, P-selectin, and E-selectin in DBD compared with LD and DCD kidneys. A
      significant increase in the expression of injury markers Kim-1, p21, and the
      cytoprotective gene heme oxygenase-1 accompanied this. Bax was increased in DCD
      kidneys, and Bcl-2 was decreased in DBD kidneys. After 2 hr of CI in the LD group
      and 18 hr in the DBD and DCD groups, gene expression levels were similar to those
      found after retrieval. During 18 hr of cold storage, expression levels of these
      genes did not change. In DCD and DBD kidneys, early apoptosis increased after CI.
      DISCUSSION/CONCLUSION: The gene expression profile in DBD kidneys represents an
      inflammatory and injury response to brain death. In contrast, DCD kidneys show
      only mild up-regulation of inflammatory and injury genes. These results may imply
      why delayed graft function in DCD kidneys does not have the deleterious effect it
      has on DBD kidneys.

PMID- 24901653
TI  - Rational design of highly responsive pH sensors based on DNA i-motif.
AB  - Availability of strategies for molecular biosensing over a finely adjustable
      dynamic range is essential for understanding and controlling vital biological
      processes. Herein we report design principles of highly responsive pH sensors
      based on a DNA i-motif where both response sensitivity and transition midpoint
      can be tuned with high precision over the physiologically relevant pH interval.
      The tuning is accomplished via rational manipulations of an i-motif structure as
      well as incorporation of allosteric control elements. This strategy delivers
      molecular sensing systems with a transition midpoint tunable with 0.1 pH units
      precision and with a total response range as narrow as 0.2 pH units which can be
      adjusted to a variety of outputs (e.g., fluorescent readout). The potential of
      the presented approach is not limited by pH sensing but may extend toward
      manipulation of other quadruplex based structures or the development of
      ultraresponsive elements for artificial molecular machines and signaling systems.

PMID- 24901652
TI  - Quantum mechanical analysis of nonenzymatic nucleotidyl transfer reactions:
      kinetic and thermodynamic effects of beta-gamma bridging groups of dNTP
      substrates.
AB  - Rate (k) and equilibrium (K) constants for the reaction of tetrahydrofuranol with
      a series of Mg(2+) complexes of methyl triphosphate analogues, CH3O-P(O2)-O-P(O2)
      X-PO3(4-), X = O, CH2, CHCH3, C(CH3)2, CFCH3, CHF, CHCl, CHBr, CFCl, CF2, CCl2,
      and CBr2, forming phosphate diester and pyrophosphate or bisphosphonate in
      aqueous solution were evaluated by B3LYP/TZVP//HF/6-31G* quantum chemical
      calculations and Langevin dipoles and polarized continuum solvation models. The
      calculated log k and log K values were found to depend linearly on the
      experimental pKa4 of the conjugate acid of the corresponding pyrophosphate or
      bisphosphonate leaving group. The calculated slopes of these Bronsted linear free
      energy relationships were betalg = -0.89 and betaeq = -0.93, respectively. The
      studied compounds also followed the linear relationship Deltalog k = 0.8Deltalog
      K, which became less steep, Deltalog k = 0.6Deltalog K, after the range of
      studied compounds was extended to include analogues that were doubly protonated
      on gamma-phosphate, CH3O-P(O2)-O-P(O2)-X-PO3H2(2-). The scissile Palpha-Olg bond
      length in studied methyl triphosphate analogues slightly increases with
      decreasing pKa of the leaving group; concomitantly, the CH3OPalpha(O2) moiety
      becomes more positive. These structural effects indicate that substituents with
      low pKa can facilitate both Palpha-Olg bond breaking and the Palpha-Onuc bond
      forming process, thus explaining the large negative betalg calculated for the
      transition state geometry that has significantly longer Palpha-Onuc distance than
      the Palpha-Olg distance. 

PMID- 24901654
TI  - Placental weight and foetal growth rate as predictors of ischaemic heart disease
      in a Swedish cohort.
AB  - Studies on placental size and cardiovascular disease have shown inconsistent
      results. We followed 10,503 men and women born in Uppsala, Sweden, 1915-1929 from
      1964 to 2008 to assess whether birth characteristics, including placental weight
      and placenta/birth weight ratio, were predictive of future ischaemic heart
      disease (IHD). Adjustments were made for birth cohort, age, sex, mother's parity,
      birth weight, gestational age and social class at birth. Placental weight and
      birth weight were negatively associated with IHD. The effect of placental weight
      on IHD was stronger in individuals from medium social class at birth and in those
      with low education. Men and women from non-manual social class at birth had the
      lowest risk for IHD as adults. We conclude that low foetal growth rate rather
      than placental weight was more predictive of IHD in the Swedish cohort. However,
      the strong effect of social class at birth on risk for IHD did not appear to be
      mediated by foetal growth rate. 

PMID- 24901655
TI  - Adolescent experience predicts longevity: evidence from historical epidemiology.
AB  - Human development reportedly includes critical and sensitive periods during which
      environmental stressors can affect traits that persist throughout life.
      Controversy remains over which of these periods provides an opportunity for such
      stressors to affect health and longevity. The elaboration of reproductive biology
      and its behavioral sequelae during adolescence suggests such a sensitive period,
      particularly among males. We test the hypothesis that life expectancy at age 20
      among males exposed to life-threatening stressors during early adolescence will
      fall below that among other males. We apply time-series methods to cohort
      mortality data in France between 1816 and 1919, England and Wales between 1841
      and 1919, and Sweden between 1861 and 1919. Our results indicate an inverse
      association between cohort death rates at ages 10-14 and cohort life expectancy
      at age 20. Our findings imply that better-informed and more strategic management
      of the stressors encountered by early adolescents may improve population health. 

PMID- 24901656
TI  - Maternal depression and foetal responses to novel stimuli: insights from a socio
      economically disadvantaged Indian cohort.
AB  - Maternal stress during pregnancy has pervasive effects on stress responsivity in
      children. This study is the first to test the hypothesis that maternal prenatal
      depression, as observed in South India, may be associated with how foetuses
      respond to a potentially stressful stimulus. We employed measures of foetal heart
      rate at baseline, during exposure to a vibroacoustic stimulus, and post
      stimulation, to study patterns of response and recovery in 133 third trimester
      foetuses of depressed and non-depressed mothers. We show that the association
      between maternal depression and foetal stress responsivity is U-shaped with
      foetuses of mothers with high and low depression scores demonstrating elevated
      responses, and poorer recovery, than foetuses of mothers with moderate levels.
      The right amount of intra-uterine stimulation is important in conditioning
      foetuses towards optimal regulation of their stress response. Our results imply
      that, in certain environmental contexts, exposure to moderate amounts of intra
      uterine stress may facilitate this process. 

PMID- 24901657
TI  - Impact of maternal hyperlipidic hypercholesterolaemic diet on male reproductive
      organs and testosterone concentration in rabbits.
AB  - The concept of Developmental Origins of Health and Disease initially stemmed from
      the developmental programming of metabolic diseases. Reproductive functions and
      fertility in adulthood may also be programmed during foetal development. We
      studied the impact of dietary-induced maternal hyperlipidaemia and
      hypercholesterolaemia (HH), administered at 10 weeks of age and throughout the
      gestation and lactation, on male reproductive functions of rabbit offspring. Male
      rabbits born to HH dams and fed a control diet had significantly lighter testes
      and epididymes compared with rabbits born to control dams at adulthood. No
      significant changes in sperm concentration, sperm DNA integrity and sperm
      membrane composition were observed, but serum-free testosterone concentrations
      were decreased in HH males. This study confirms the importance of maternal
      metabolic status for the development of male reproductive organs. 

PMID- 24901658
TI  - Association of early postnatal growth trajectory with body composition in term
      low birth weight infants.
AB  - Growth acceleration or catch-up growth (CUG) in early infancy is a plausible risk
      factor for later obesity and cardiovascular disease. We postulate that this risk
      may be mediated by an adverse programming of body composition by CUG in early
      infancy. The study was aimed at evaluating the association between the pattern of
      gain in weight and length of term low birth weight (LBW) infants from birth to 6
      months, with fat mass percent (FM%) at 6 months. Term healthy singleton LBW
      infants were enrolled. Baby's weight and length z-scores were measured at birth
      and three follow-up visits. Body composition was measured by dual-energy
      absorptiometry at last visit. A total of 54 babies (28 boys) were enrolled. The
      mean birth weight and gestation were 2175+/-180 g and 37.6+/-0.6 weeks. Follow-up
      visits were at 1.4+/-0.0, 3.0+/-0.3 and 7.2+/-0.8 months. The proportion of
      babies who showed CUG [increase in weight for age z-score (?WAZ)>0.67] from birth
      to 1.4, 3.0 and 7.2 months was 29.6, 26.4 and 48.5%, respectively. The mean FM%
      at 7.2 months was 16.6+/-7.8%. Infants with greater ?WAZ from birth to 3 and 7.2
      months had significantly greater FM% at 7.2 months after adjusting for current
      age, size and gender. Infants with early CUG (<1.4 months) had higher FM% than
      infants with no CUG. We conclude that earlier and greater increment in WAZ is
      positively associated with FM%. 

PMID- 24901659
TI  - Challenges in modelling the random structure correctly in growth mixture models
      and the impact this has on model mixtures.
AB  - Lifecourse trajectories of clinical or anthropological attributes are useful for
      identifying how our early-life experiences influence later-life morbidity and
      mortality. Researchers often use growth mixture models (GMMs) to estimate such
      phenomena. It is common to place constrains on the random part of the GMM to
      improve parsimony or to aid convergence, but this can lead to an autoregressive
      structure that distorts the nature of the mixtures and subsequent model
      interpretation. This is especially true if changes in the outcome within
      individuals are gradual compared with the magnitude of differences between
      individuals. This is not widely appreciated, nor is its impact well understood.
      Using repeat measures of body mass index (BMI) for 1528 US adolescents, we
      estimated GMMs that required variance-covariance constraints to attain
      convergence. We contrasted constrained models with and without an autocorrelation
      structure to assess the impact this had on the ideal number of latent classes,
      their size and composition. We also contrasted model options using simulations.
      When the GMM variance-covariance structure was constrained, a within-class
      autocorrelation structure emerged. When not modelled explicitly, this led to
      poorer model fit and models that differed substantially in the ideal number of
      latent classes, as well as class size and composition. Failure to carefully
      consider the random structure of data within a GMM framework may lead to
      erroneous model inferences, especially for outcomes with greater within-person
      than between-person homogeneity, such as BMI. It is crucial to reflect on the
      underlying data generation processes when building such models. 

PMID- 24901660
TI  - Maternal supplementation with fishmeal protects against late gestation endotoxin
      induced fetal programming of the ovine hypothalamic-pituitary-adrenal axis.
AB  - Adverse uterine environments caused by maternal stress (such as bacterial
      endotoxin) can alter programming of the fetal hypothalamic-pituitary-adrenal axis
      (HPAA) rendering offspring susceptible to various adulthood diseases. Thus,
      protection against this type of stress may be critical for ensuring offspring
      health. The present study was designed to determine if maternal supplementation
      with omega-3 polyunsaturated fatty acids (n-3 PUFAs) during pregnancy helps to
      protect against stress-induced fetal programming. Briefly, 53 ewes were fed a
      diet supplemented with fishmeal (FM) or soybean meal (SM) from day 100 of
      gestation (gd100) through lactation. On gd135, half the ewes from each dietary
      group were challenged with either 1.2 MUg/kg Escherichia coli lipopolysaccharide
      (LPS) endotoxin, or saline as the control. The offspring's cortisol response to
      weaning stress was assessed 50 days postpartum by measuring serum cortisol
      concentrations 0, 6 and 24 h post weaning. Twenty-four hours post-weaning, lambs
      were subjected to an adrenocorticotropic hormone (ACTH) challenge (0.5 MUg/kg)
      and serum cortisol concentrations were measured 0, 0.25, 0.5, 1 and 2 h post
      injection. At 5.5 months of age, offspring were also challenged with 400 ng/kg of
      LPS, and serum cortisol concentrations were measured 0, 2, 4 and 6 h post
      challenge. Interestingly, female offspring born to FM+LPS mothers had a greater
      cortisol response to weaning and endotoxin challenge compared with the other
      treatments, while female offspring born to SM+LPS mothers had a faster cortisol
      response to the ACTH stressor. Additionally, males born to FM+LPS mothers had a
      greater cortisol response to the ACTH challenge than the other treatments.
      Overall, FM supplementation during gestation combined with LPS challenge alters
      HPAA responsiveness of the offspring into adulthood. 

PMID- 24901661
TI  - Leptin levels at birth and infant growth: the EPOCH study.
AB  - OBJECTIVE: To examine the association of cord blood leptin with body mass index
      (BMI) growth velocity from birth to 12 months of age among infants exposed and
      not exposed to over-nutrition in utero (defined as maternal overweight/obesity or
      presence of gestational diabetes). METHODS: 185 infants enrolled in the Exploring
      Perinatal Outcomes among Children study (76 exposed and 109 not exposed) had
      leptin and insulin measured in cord blood. Longitudinal weight and length
      measures in the first 12 months of life (average 4 per participant) obtained from
      medical records were used to compute BMI growth rates. Mixed models were used to
      examine associations of cord blood leptin with growth. RESULTS: Compared with
      unexposed infants, those exposed had significantly higher cord blood insulin
      (8.64 v. 6.97 uU/ml, P<0.01) and leptin levels (8.89 v. 5.92 ng/ml, P=0.05) as
      well as increased birth weights (3438.04 v. 3306.89 g, P=0.04). There was an
      inverse relationship between cord leptin levels and BMI growth from birth to 12
      months of age (P=0.005); however, exposure to over-nutrition in utero did not
      significantly modify this association (P=0.59). CONCLUSION: We provide support of
      a possible operational feedback mechanism by which lower cord blood leptin levels
      are associated with faster infant growth in the first year of life. Our data do
      not tend to support the hypothesis that this mechanism is altered in infants
      exposed to over-nutrition in utero; however our sample is too small to provide
      sufficient evidence. Larger epidemiological studies are needed to elucidate the
      mechanisms responsible for increased propensity for obesity in exposed offspring.

PMID- 24901662
TI  - Effects of maternal separation on the dietary preference and behavioral satiety
      sequence in rats.
AB  - This study investigated the effects of maternal separation on the feeding
      behavior of rats. A maternal separation model was used on postnatal day 1 (PND1),
      forming the following groups: in the maternal separation (MS) group, pups were
      separated from their mothers each day from PND1 to PND14, whereas in the control
      (C) group pups were kept with their mothers. Subgroups were formed to study the
      effects of light and darkness: control with dark and light exposure, female and
      male (CF and CM), and maternal separation with dark and light exposure, female
      and male (SDF, SDM, SLF and SLM). Female rats had higher caloric intake relative
      to body weight compared with male controls in the dark period only (CF=23.3+/-0.5
      v. CM=18.2+/-0.7, P<0.001). Macronutrient feeding preferences were observed, with
      male rats exhibiting higher caloric intake from a protein diet as compared with
      female rats (CF=4.1+/-0.7, n=8 v. CM=7.0+/-0.5, n=8, P<0.05) and satiety
      development was not interrupted. Female rats had a higher adrenal weight as
      compared with male rats independently of experimental groups and exhibited a
      higher concentration of serum triglycerides (n=8, P<0.001). The study indicates
      possible phenotypic adjustments in the structure of feeding behavior promoted by
      maternal separation, especially in the dark cycle. The dissociation between the
      mother's presence and milk intake probably induces adjustments in feeding
      behavior during adulthood. 

PMID- 24901664
TI  - Birth weight and cognitive function in early adulthood: the Australian Aboriginal
      birth cohort study.
AB  - It has been suggested that in addition to genetic factors, fetal and post-natal
      growth influence cognition in early adulthood. However, most studies have been in
      developed populations, so it is unclear if the same findings would be seen in
      other, less developed, settings, and have used testing tools not applicable to an
      Australia Aboriginal population. This study investigated the relationships
      between cognitive function in early adulthood and birth weight and contemporary
      height. Simple reaction time (SRT), choice reaction time (CRT) and working memory
      (WM) were assessed using the CogState battery. A significant association was seen
      between birth weight and SRT in early adulthood, but not with the other two
      cognitive measures. Urban dwellers had significantly shorter SRT and CRT than
      their remote counterparts. Contemporary body mass index and maternal age were
      associated with CRT. Only fetal growth restriction was associated with WM, with
      greater WM in those with restricted growth. No associations were seen with
      contemporary height. These results suggest that fetal growth may be more
      important than the factors influencing post-natal growth in terms of cognition in
      early adulthood in this population, but that the associations may be inconsistent
      between cognitive outcomes. Further research is required to identify whether
      similar associations are seen in other, similar, populations and to assess why
      differences in cognitive outcome measures are seen. 

PMID- 24901663
TI  - Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and
      body composition.
AB  - Maternal high-fat diet consumption and obesity have been shown to program long
      term obesity and lead to impaired glucose tolerance in offspring. Many rodent
      studies, however, use non-purified, cereal-based diets as the control for
      purified high-fat diets. In this study, primiparous ICR mice were fed purified
      control diet (10-11 kcal% from fat of lard or butter origin) and lard (45 or 60
      kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before
      mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female
      mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose
      tolerance but those females fed the lard-based diets showed normal glucose
      disposal following a glucose challenge. High-fat diet consumption by female mice
      of all groups decreased lean to fat mass ratios during the 4th week of diet
      treatment compared with those mice consuming the 10-11% fat diets. All females
      were bred to male mice and pregnancy and offspring outcomes were monitored. The
      body weight of pups born to 45% lard-fed dams was significantly increased before
      weaning, but only female offspring born to 32% butter-fed dams exhibited long
      term body weight increases. Offspring glucose tolerance and body composition were
      measured for at least 1 year. Minimal, if any, differences were observed in the
      offspring parameters. These results suggest that many variables should be
      considered when designing future high-fat diet feeding and maternal obesity
      studies in mice. 

PMID- 24901665
TI  - Prenatal programming of obesity in a swine model of leptin resistance: modulatory
      effects of controlled postnatal nutrition and exercise.
AB  - The main role of early nutritional programming in the current rise of obesity and
      associated diseases is well known. However, translational studies are mostly
      based in postnatal food excess and, thus, there is a paucity of information on
      the phenotype of individuals with prenatal deficiencies but adequate postnatal
      conditions. Thus, we assessed the effects of prenatal programming (comparing
      descendants from females fed with a diet fulfilling 100 or only 50% of their
      nutritional requirements for pregnancy) on gene expression, patterns of growth
      and fattening, metabolic status and puberty attainment of a swine model of
      obesity/leptin resistance with controlled postnatal nutrition and opportunity of
      exercise. Maternal restriction was related to changes in the relationships among
      gene expression of positive (insulin-like growth factors 1 and 2) and negative
      (myostatin) regulators of muscle growth, with negative correlations in gilts from
      restricted pregnancies and positive relationships in the control group. In spite
      of these differences, the patterns of growth and fattening and the metabolic
      features during juvenile growth were similar in control gilts and gilts from
      restricted pregnancies. Concomitantly, there was a lack of differences in the
      timing of puberty attainment. However, after reaching puberty and adulthood,
      females from restricted pregnancies were heavier and more corpulent than control
      gilts, though such increases in weight and size were not accompanied by increases
      in adiposity. In conclusion, in spite of changes in gene expression induced by
      developmental programming, the propensity for higher weight and adiposity of
      individuals exposed to prenatal malnutrition may be modulated by controlled food
      intake and opportunity of physical exercise during infant and juvenile
      development. 

PMID- 24901666
TI  - Impact of a walking intervention during pregnancy on post-partum weight retention
      and infant anthropometric outcomes.
AB  - Few studies have investigated the impact of lifestyle interventions during
      pregnancy on post-partum weight retention and infant growth. Thirty seven
      previously non-exercising, overweight or obese pregnant women were randomly
      assigned to a walking intervention or non-intervention control. For the follow-up
      study, weight of the mother and weight, length and body composition of the infant
      were collected at 1 month post-partum (n=37) and 6 months post-partum (n=33).
      Analysis of variance and linear regression were conducted to determine the
      differences and association in maternal post-partum weight retention and child
      outcomes. At 6 months post-partum, weight retention of obese women in the
      intervention group (Int-OB) was -0.10+/-8.11 kg; while, obese women in the
      control group (Con-OB) was 6.35+/-7.47 kg. A significantly higher percentage of
      Con-OB women retained more than 5 kg at 6 months post-partum (P=0.046). Even
      though statistically non-significant between the groups, the growth trend
      observed among offspring of obese women in the control group was consistently
      higher than the offspring of obese women in the intervention group from birth to
      6-months. Third trimester gestational weight gain rate significantly predicted 6
      m weight-for-length z-score after controlling for birth weight, treatment group
      and pre-pregnancy body mass index (r 2=0.31, beta=1.75, P=0.03). The reduced post
      partum weight retention observed among the obese women in the intervention group
      may be explained in part by the lifestyle modification during pregnancy. 

PMID- 24901667
TI  - 4-amino-1-hydroxy-2-oxo-1,8-naphthyridine-containing compounds having high
      potency against raltegravir-resistant integrase mutants of HIV-1.
AB  - There are currently three HIV-1 integrase (IN) strand transfer inhibitors
      (INSTIs) approved by the FDA for the treatment of AIDS. However, the emergence of
      drug-resistant mutants emphasizes the need to develop additional agents that have
      improved efficacies against the existent resistant mutants. As reported herein,
      we modified our recently disclosed 1-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine
      3-carboxamides IN inhibitors to develop compounds that have improved efficacies
      against recombinant IN in biochemical assays. These new compounds show single
      digit nanomolar antiviral potencies against HIV vectors that carry wild-type (WT)
      IN in a single round replication assay and have improved potency against vectors
      harboring the major forms of drug resistant IN mutants. These compounds also have
      low toxicity for cultured cells, which in several cases, results in selectivity
      indices (CC50/EC50) of greater than 10000. The compounds have the potential, with
      additional structural modifications, to yield clinical agents that are effective
      against the known strains of resistant viruses. 

PMID- 24901668
TI  - Highly dispersed SrTiO3 nanocubes from a rapid sol-precipitation method.
AB  - SrTiO3 nanocubes and their hyperstable nanocrystalline sols were synthesized by a
      rapid sol-precipitation method under atmospheric pressure. Using triethylene
      glycol (TEG) to control the hydrolysis rate of tetrabutyl titanate, the SrTiO3
      nanocrystalline sol was obtained in as little time as 2 h. The formation kinetics
      of the SrTiO3 nanocubes indicated that controlled hydrolysis is critical to the
      generation of a well defined cubic shape. The Fourier transform infrared (FT-IR)
      spectrum confirms the existence of TEG molecules on the surface of the particles
      and explains the high dispersion of the nanocubes in polar solvents. Owing to the
      large specific surface area (99.065 m(2) g(-1)), cubic SrTiO3 nanocrystals showed
      enhanced photocatalytic activity. A high-quality SrTiO3 nanocrystal film was
      prepared by spin-coating of the hyperstable sol at 100-160  degrees C, providing
      a new low-temperature route for the fabrication of perovskite thin films.

PMID- 24901669
TI  - Can unaided non-linguistic measures predict cochlear implant candidacy?
AB  - OBJECTIVE: To determine if unaided, non-linguistic psychoacoustic measures can be
      effective in evaluating cochlear implant (CI) candidacy. STUDY DESIGN:
      Prospective split-cohort study including predictor development subgroup and
      independent predictor validation subgroup. SETTING: Tertiary referral center.
      SUBJECTS: Fifteen subjects (28 ears) with hearing loss were recruited from
      patients visiting the University of Washington Medical Center for CI evaluation.
      METHODS: Spectral-ripple discrimination (using a 13-dB modulation depth) and
      temporal modulation detection using 10- and 100-Hz modulation frequencies were
      assessed with stimuli presented through insert earphones. Correlations between
      performance for psychoacoustic tasks and speech perception tasks were assessed.
      Receiver operating characteristic curve analysis was performed to estimate the
      optimal psychoacoustic score for CI candidacy evaluation in the development
      subgroup and then tested in an independent sample. RESULTS: Strong correlations
      were observed between spectral-ripple thresholds and both aided sentence
      recognition and unaided word recognition. Weaker relationships were found between
      temporal modulation detection and speech tests. Receiver operating characteristic
      curve analysis demonstrated that the unaided spectral-ripple discrimination shows
      a good sensitivity, specificity, positive predictive value, and negative
      predictive value compared to the current gold standard, aided sentence
      recognition. CONCLUSION: Results demonstrated that the unaided spectral-ripple
      discrimination test could be a promising tool for evaluating CI candidacy.

PMID- 24901670
TI  - Transcanal blind sac closure of the external auditory canal after skull base
      surgery to treat CSF leak: technique and results.
AB  - OBJECTIVE: To report outcomes of a novel transcanal blind sac closure technique
      of the external auditory canal (EAC) with obliteration of the Eustachian tube
      orifice to treat CSF leaks after skull base surgery. STUDY DESIGN: Clinical
      capsule report. SETTING: University hospital. PATIENTS: Ten patients who have
      undergone a transcanal blind sac closure of the EAC after skull base surgery to
      treat CSF leak between 2004 and 2012. INTERVENTIONS: Transcanal blind sac closure
      of the EAC. MAIN OUTCOME MEASURES: Resolution rate of postoperative CSF leak,
      time to final resolution of CSF leak, and complications. RESULTS: The CSF leak
      resolution rate, with subsequent conservative management in some cases, is
      approximately 80%. One case of postsurgical pseudomeningocele was identified.
      CONCLUSION: Transcanal blind sac closure of the EAC with obliteration of the
      Eustachian tube orifice provides a rapid and safe method to treat CSF leak after
      skull base surgery, without the need to reenter the original surgical wound or
      mastoid cavity.

PMID- 24901671
TI  - Is teaching communication skills integrated into Spanish medical schools
      curricula?

PMID- 24901672
TI  - Photoinduced electron transfer through peptide-based self-assembled monolayers
      chemisorbed on gold electrodes: directing the flow-in and flow-out of electrons
      through peptide helices.
AB  - Photoinduced electron transfer (PET) experiments have been carried out on peptide
      self-assembled monolayers (SAM) chemisorbed on a gold substrate. The oligopeptide
      building block was exclusively formed by C(alpha)-tetrasubstituted alpha
      aminoisobutyric residues to attain a helical conformation despite the shortness
      of the peptide chain. Furthermore, it was functionalized at the C-terminus by a
      pyrene choromophore to enhance the UV photon capture cross-section of the
      compound and by a lipoic group at the N-terminus for linking to gold substrates.
      Electron transfer across the peptide SAM has been studied by photocurrent
      generation experiments in an electrochemical cell employing a gold substrate
      modified by chemisorption of a peptide SAM as a working electrode and by steady
      state and time-resolved fluorescence experiments in solution and on a gold-coated
      glass. The results show that the electronic flow through the peptide bridge is
      strongly asymmetric; i.e., PET from the C-terminus to gold is highly favored with
      respect to PET in the opposite direction. This effect arises from the polarity of
      the Au-S linkage (Au(delta+)-S(delta-), junction effect) and from the
      electrostatic field generated by the peptide helix. 

PMID- 24901673
TI  - Transformation of mercury at the bottom of the Arctic food web: an overlooked
      puzzle in the mercury exposure narrative.
AB  - We show 2008 seasonal trends of total and monomethyl mercury (THg and MeHg,
      respectively) in herbivorous (Calanus hyperboreus) and predatory (Chaetognaths,
      Paraeuchaeta glacialis, and Themisto abyssorum) zooplankton species from the
      Canadian High Arctic (Amundsen Gulf and the Canadian Beaufort Sea) in relation to
      ambient seawater and diet. It has recently been postulated that the Arctic marine
      environment may be exceptionally vulnerable to toxic MeHg contamination through
      postdepositional processes leading to mercury transformation and methylation.
      Here, we show that C. hyperboreus plays a hitherto unrecognized central role in
      mercury transformation while, itself, not manifesting inordinately high levels of
      THg compared to its prey (pelagic particulate organic matter (POM)). Calanus
      hyperboreus shifts Hg from mainly inorganic forms in pelagic POM (>99.5%) or
      ambient seawater (>90%) to primarily organic forms (>50%) in their tissue. We
      calculate that annual dietary intake of MeHg could supply only ~30% of the MeHg
      body burden in C. hyperboreus and, thus, transformation within the species,
      perhaps mediated by gut microbial communities, or bioconcentration from ambient
      seawater likely play overriding roles. Seasonal THg trends in C. hyperboreus are
      variable and directly controlled by species-specific physiology, e.g., egg laying
      and grazing. Zooplankton that prey on species such as C. hyperboreus provide a
      further biomagnification of MeHg and reflect seasonal trends observed in their
      prey. 

PMID- 24901675
TI  - Study on retardance due to well-ordered birefringent cylinders in anisotropic
      scattering media.
AB  - We report an anisotropic tissue model containing well-ordered birefringent
      cylinders. Using simulations and experiments, we examined the different
      polarization features for nonbirefringent and birefringent cylinders and analyzed
      the influence of the birefringent cylinders on the retardance obtained from
      Mueller matrix polar decomposition. For the well-ordered birefringent cylinders,
      retardance increases linearly with the intrinsic birefringence and the scattering
      coefficient. Furthermore, the cylinders with a larger diameter generate more
      retardance. Compared with the cylinder-birefringence model, in which birefringent
      medium exists between the scatterers, the intrinsic birefringence on the
      cylinders usually contributes much less to the total retardance.

PMID- 24901674
TI  - Engaging heart failure clinicians to increase palliative care referrals:
      overcoming barriers, improving techniques.
AB  - BACKGROUND: Heart failure (HF) is the most common cause of hospitalization among
      adults over the age of 65. Hospital readmission rates, mortality rates, and
      Medicare costs for patients with this disease are high. Furthermore, patients
      with HF experience a number of symptoms that worsen as the disease progresses.
      However, a small minority of patients with HF receives hospice or palliative
      care. One possible reason for this may be that the HF and palliative care
      clinicians have differing perspectives on the role of palliative care for these
      patients. AIM: The goal of the article is to offer palliative care clinicians a
      roadmap for collaborating with HF clinicians by reviewing the needs of patients
      with HF. CONCLUSIONS: This article reviews the needs of patients with HF and
      their families, the barriers to referral to palliative care for patients with HF,
      and provides suggestions for improving collaboration between palliative care and
      HF clinicians.

PMID- 24901676
TI  - Mast-cell-based fluorescence biosensor for rapid detection of major fish allergen
      parvalbumin.
AB  - In this study, we developed a rat basophilic leukemia cell (RBL-2H3) fluorescence
      sensor to detect and identify the major fish allergen parvalbumin (PV). We
      constructed and transfected a CD63-enhanced green fluorescent protein (EGFP)
      plasmid into RBL cells through a highly efficient, lipid-mediated, DNA
      transfection procedure. Stable transfectant RBL cells were then obtained for a
      cell fluorescence assay with confocal laser scanning microscopy. Results show
      that the cell surface expression of CD63 reflects degranulation, indicating that
      a fluorescence assay with these cells could efficiently measure the activation of
      antigen-stimulated transfectant cells and detect antigens with a nanogram level.
      Therefore, this cell-based fluorescence biosensor technique for detecting fish PV
      exhibits promise for quantifying fish PV after anti-PV immunoglobulin E (IgE)
      stimulation. Results show that fluorescence intensities increased with purified
      PV concentrations from 1 to 100 ng/mL, with a detection limit of 0.35 ng/mL
      [relative standard deviation (RSD) of 4.5%], confirmed by beta-hexosaminidase
      assays. These rat basophilic leukemia (RBL) mast cells transfected with the CD63
      EGFP gene and responded to PV only when they were sensitized with the specific
      IgE antibody. This demonstrates the utility of this highly sensitive biosensor
      for food allergen detection and prediction. 

PMID- 24901677
TI  - Prediction profiles for nutritional supplement use among young German elite
      athletes.
AB  - Nutritional supplements (NS) are defined as concentrated sources of nutrients and
      other substances that have a nutritional or physiological effect and that are
      used in high frequency among athletes. The study aimed to create a prediction
      profile for young elite athletes to identify those athletes who have a higher
      relative risk for using NS. The second objective was to examine the hypothesis
      that the consumption of NS paves a gateway for the use of illicit drugs and
      doping substances. A self-designed anonymous paper-and-pencil questionnaire was
      used to examine the prevalence of NS consumption, doping, and illicit drug use in
      elite athletes with a mean age of 17 years (SD = 4 years). Logistic regression
      analysis was employed to assess whether NS consumption can be predicted by
      independent variables (e.g., biographical data, training characteristics, drug
      consumption behavior) to create the prediction profile for NS use. 55% and 5% of
      the athletes (n = 536) responded positively to having used NS and illicit drugs,
      respectively. Nutritional supplement consumption was positively correlated with
      age (OR: 1.92; CI: 1.21 to 3.05), the desire to enhance performance to become an
      Olympic or World Champion (OR: 3.72; CI: 2.33 to 6.01), and being educated about
      NS (OR: 2.76; CI: 1.73 to 4.45). It was negatively correlated with training
      frequency (OR: 0.55; CI: 0.35 to 0.86) and the use of nicotine (OR: 0.29; CI: 0.1
      to 0.74) but did not correlate with illicit drug use and alcohol consumption. The
      present results show that NS are used on a large scale in elite sports. The
      prediction profile presented in this article may help to identify those athletes
      who have a high risk for using NS to plan potential education and prevention
      models more individually. 

PMID- 24901678
TI  - Image of the month-quiz case.

PMID- 24901679
TI  - Image of the month-quiz case.

PMID- 24901680
TI  - Acute symptomatic Meckel diverticulum management. Our experience on seven
      consecutive cases.
AB  - Meckel's diverticulum (MD ) is the most common congenital anomaly of the
      gastrointestinal tract. We revalued clinical records of patients discharged from
      Unit of Urgent and General Surgery of Highly Specialized Hospital "A.O.R.N.
      Antonio Cardarelli" of Naples with diagnosis of acute pathology associated to
      complicated MD from 1(st) January 2011 to 30(th) November 2012. Seven consecutive
      cases have been chosen: five males (71,4%) and two females (28,6%). The age
      ranges over from 13 to 50 years with a 28 years average. Four of them were
      submitted to emergency surgical intervention for hemorrhage from gastro-enteric
      tract (57%), two for bowel obstruction (29%) and one for acute appendicitis
      (14%). In all cases sample was send to histological examination. Two samples
      showed normal epithelial mucosa. Four of them showed ectopic mucosa inside the
      diverticulum: three gastric and one pancreatic ectopic mucosa focal areas. The
      last case showed normal epithelial cells but with ulcerated and hemorrhagic
      areas. Four samples of patients with hemorrhage from gastroenteric tract showed
      at histological examination: a case of normal mucosa, a case of gastric mucosa
      areas, one of pancreatic ectopic tissue and the last with normal mucosa but
      ulcerated and with bleeding areas.In our experience we never speculated that
      acute symptomatology depended on complicated MD and diagnosis was always done
      during laparotomy. We think that MD removal is always the correct choice, so that
      future complications such as neoplasm can be avoided. MD simple resection by
      Stapler at the base of diverticulum is the correct choice.

PMID- 24901682
TI  - Transanal endoscopic surgery with total wall excision is required with rectal
      adenomas due to the high frequency of adenocarcinoma.
AB  - BACKGROUND: Colorectal adenomatous polyps are considered premalignant lesions,
      although a high percentage are already malignant at the time of their removal.
      Full-thickness excision in patients with adenoma detected in preoperative biopsy
      enables much more accurate pathology examination and has shown that local surgery
      is appropriate for T1 adenocarcinoma. OBJECTIVE: To determine whether full
      thickness excision during transanal endoscopic surgery is the treatment of choice
      for rectal adenoma, and to identify possible predictors of invasive
      adenocarcinoma associated with this type of lesion. DESIGN: Prospective,
      observational study. SETTING: The study was conducted at a university teaching
      hospital. PATIENTS: All patients scheduled for transanal endoscopic surgery after
      detection of adenoma in a preoperative biopsy between June 2004 and February 2013
      entered the study. MAIN OUTCOME MEASURES: The principal variable was the presence
      of invasive adenocarcinoma in the pathology study. Other study variables were the
      epidemiological variables sex and age; the clinical variables tumor size, number
      of quadrants affected, distance from the anal verge, and tumor location; and the
      morphological variables tumor aspect, degree of dysplasia, preoperative biopsy
      (tubulo-villous), endorectal ultrasound, and pelvic MRI stage. Variables found to
      be related to the risk of malignancy in rectal adenomas were evaluated using
      univariate and multivariate analysis. RESULTS: Of 471 patients who underwent
      surgery, 277 had a preoperative diagnosis of adenoma. Final pathology studies
      showed 52 (18.8%) invasive adenocarcinomas, among which 27 were pT1 (52%), 16 pT2
      (30.7%), and 9 pT3 (17.3%). Factors predictive of invasive adenocarcinoma were
      sessile morphology (OR 3.2, 95%CI 1.4-7.1), high-grade dysplasia (OR 2.3, 95%CI
      1.2-4.8), and endorectal ultrasound stage uT2-T3 (OR 3.8, 95%CI 1.6-9).
      LIMITATIONS: The limitations are derived from the observational design.
      CONCLUSIONS: In this sample, half of the adenocarcinomas from adenomas were T1
      adenocarcinomas. Because a high proportion of rectal adenomas are, in fact,
      invasive adenocarcinomas, full-thickness excision is appropriate.

PMID- 24901681
TI  - Multicenter study of outcome in relation to the type of resection in rectal
      cancer.
AB  - BACKGROUND: A surgical teaching and auditing program has been implemented to
      improve the results of treatment for patients with rectal cancer. OBJECTIVE: The
      aim of this study was to assess the treatment and outcome in patients resected
      for rectal cancer, focusing on differences relating to the type of resection.
      DESIGN: This was an observational study. SETTINGS: The study took place
      throughout the network of hospitals that compose the National Health Service in
      Spain. PATIENTS: This study included a consecutive cohort of 3355 patients from
      the Spanish Rectal Cancer Project. The data of patients who were operated on
      electively, with curative intent, by anterior resection (n = 2333 [69.5%]),
      abdominoperineal excision (n = 774 [23.1%]), and Hartmann procedure (n = 248
      [7.4%]) between March 2006 and May 2010 were analyzed. MAIN OUTCOME MEASURES:
      Clinical, pathologic, and outcome results were analyzed in relation to the type
      of surgery performed. RESULTS: After a median follow-up time of 37 months
      (interquartile range, 30-48 months), bowel perforations were found to be more
      common in the Hartmann procedure (12.6%) and abdominoperineal groups (10.1%) than
      in the anterior resection group (2.3%; p < 0.001). Involvement of the
      circumferential resection margin was also more common in the Hartmann (16.6%) and
      abdominoperineal groups (14.3%) than in the anterior resection group (6.6%; p <
      0.001). Multivariate analysis showed a negative influence on local recurrence,
      metastasis, survival for advanced stage, intraoperative perforation, invaded
      circumferential margin, and Hartmann procedure. However, abdominoperineal
      excision did not significantly influence local recurrence (HR, 0.945; 95% CI,
      0.571-1.563; p = 0.825). LIMITATIONS: The main weakness of this study was the
      voluntary nature of registration in the Spanish Rectal Cancer Project.
      CONCLUSIONS: Although bowel perforation and involvement of the circumferential
      resection margin were more common after abdominoperineal excision than after
      anterior resection, this study did not identify abdominoperineal excision as a
      determinant of local recurrence in the context of 3 years of median follow-up.

PMID- 24901683
TI  - Clinical impact of elastic laminal invasion in colon cancer: elastic laminal
      invasion-positive stage II colon cancer is a high-risk equivalent to stage III.
AB  - BACKGROUND: Elastic laminal invasion is defined as tumor invasion beyond the
      peritoneal elastic lamina. It is one of the factors affecting the prognosis of
      patients with colon cancer. OBJECTIVE: This study aimed to investigate the
      clinical impact of elastic laminal invasion in colon cancer and the magnitude of
      the worse prognosis of elastic laminal invasion-positive, node-negative patients.
      DESIGN: This was a retrospective cohort study. SETTINGS: This study reviewed data
      from a tertiary care cancer center in Japan. PATIENTS: The records of 436
      patients with pT3 or pT4a colon cancer who underwent curative resection between
      January 1996 and December 2006 were reviewed. MAIN OUTCOME MEASURES: The primary
      outcome measure was recurrence-free survival. Cox regression analyses established
      the factors associated with recurrence-free survival. Six groups formed by
      combining the factors were compared. RESULTS: Of the patients with pT3 disease,
      those who were positive for elastic laminal invasion had a 5-year recurrence-free
      survival rate of 73.8% compared with a rate of 85.0% in those who were negative
      for elastic laminal invasion and 53.5% in patients with pT4 disease. Three
      unfavorable prognostic factors were identified, including lymph node metastasis,
      positive elastic laminal invasion, and a lack of adjuvant chemotherapy. Log-rank
      analysis revealed statistically significant differences in recurrence-free
      survival between group 1 (node negative, elastic laminal invasion negative, and
      no adjuvant chemotherapy) and group 3 (node negative, elastic laminal invasion
      positive, and no adjuvant chemotherapy). The HR for group 1 compared with group 3
      was 0.49 (95% CI, 0.27-0.90). Furthermore, the HRs for group 2 (node positive,
      elastic laminal invasion negative, and received adjuvant chemotherapy) and group
      4 (node positive, elastic laminal invasion positive, and received adjuvant
      chemotherapy) vs group 3 were 0.77 (95% CI, 0.35-1.69) and 1.36 (95% CI, 0.62
      2.98). LIMITATIONS: Our study has limited prediction accuracy of our prognostic
      stratification, and an analysis of small subgroups may not have been capable of
      detecting significant differences. In addition, a wide range of hematoxylin and
      eosin- and elastica-stained slides were examined per case. CONCLUSIONS: Elastic
      laminal invasion adversely influences prognosis in pT3 and pT4a colon cancer.
      Although elastic laminal invasion positivity does not affect prognosis in node
      positive patients receiving adjuvant chemotherapy, node-negative patients with
      elastic laminal invasion have a similar risk of recurrence as node-positive
      patients.

PMID- 24901684
TI  - Lymph node metastases in the gastrocolic ligament in patients with colon cancer.
AB  - BACKGROUND: Long-term survival after colorectal cancer may be improved by more
      extensive resection of the primary tumor and lymph nodes. Resection of the
      gastroepiploic and infrapyloric lymph nodes in the gastrocolic ligament has been
      proposed as a standard procedure when resecting tumors located in the proximity
      of the flexures or in the transverse colon. OBJECTIVE: The purpose of this work
      was to present our findings of metastases in the gastrocolic ligament in a
      consecutive series of patients. DESIGN: This was a single-center retrospective
      study. SETTINGS: The study was conducted in a colorectal cancer center. PATIENTS:
      All of the colon adenocarcinoma resections with relevant tumor location from June
      1, 2008, to December 31, 2012 were included in this study. MAIN OUTCOME MEASURES:
      The presence of lymph node metastases in the gastrocolic ligament in colon
      adenocarcinomas located in the proximity of the flexures or in the transverse
      colon was measured. RESULTS: Gastrocolic resection was performed in 130 patients.
      Thirty-two patients were excluded because of a lack of information about
      gastrocolic lymph node status in the pathology reports. Median age of the
      remaining 98 patients was 70 years (range, 30-90 years), and 57% were men.
      Gastrocolic lymph nodes were found in 86 specimens (88%) with a median number of
      4 lymph nodes (range, 0-16 lymph nodes). Thirty-four patients (35%) had mesocolic
      lymph node metastases. Gastrocolic lymph node metastases were found in 4 (12%) of
      these 34 patients and in 4% of all 98 included patients. Gastrocolic lymph node
      metastases were related to perineural invasion (p > 0.001). LIMITATIONS:
      Limitations of this study include the retrospective design, size of material, and
      lack of gastrocolic ligament lymph node status in the pathology report in some
      patients. CONCLUSIONS: Metastases in the gastroepiploic or infrapyloric lymph
      nodes can be found in patients with tumors located in the proximity of the
      flexures or in the transverse colon. Further studies are needed to reveal the
      clinical relevance of this finding, with special focus on recurrence risk and
      long-term survival.

PMID- 24901685
TI  - Utilization of colonoscopy and pathology reports for identifying patients meeting
      the world health organization criteria for serrated polyposis syndrome.
AB  - BACKGROUND: Serrated polyposis syndrome is a rare syndrome associated with an
      increased risk for colorectal cancer. The World Health Organization criteria were
      established to standardize the diagnosis and management of patients afflicted
      with serrated polyposis. Although useful, the criteria may not be ideal for the
      initial screening of at-risk populations. OBJECTIVE: The aim of this study was to
      examine the use of a minimal cutoff point of serrated lesions to increase the
      yield of serrated polyposis cases. DESIGN: This was a retrospective review of
      colonoscopy and pathology reports to identify patients who met the World Health
      Organization criteria for serrated polyposis. SETTING: This study was conducted
      at a tertiary cancer care referral center. PATIENTS: Five hundred patients who
      had at least 2 pathologically confirmed hyperplastic polyps and/or sessile
      serrated adenomas/polyps diagnosed between 1999 and 2009 were assessed. MAIN
      OUTCOME MEASURES: The primary outcome measure was the number of serrated
      polyposis cases. RESULTS: Forty of the 500 (8%) patients met the World Health
      Organization criteria for serrated polyposis syndrome. Patients underwent a
      median of 4 colonoscopies (range, 1-23) before satisfying the criteria, and only
      1 (3%) patient met the criteria for diagnosis during the initial colonoscopy. All
      16 patients with a history of colorectal cancer were only diagnosed with serrated
      polyposis either at the time of their cancer diagnosis or during postoperative
      colonoscopies. Only 5 of the 40 (13%) patients were enrolled in our institutional
      Hereditary Colorectal Cancer Family Registry before our study for prospective
      serrated lesion tracking and colorectal cancer screening. LIMITATIONS: This tool
      requires validation in a prospective setting. CONCLUSIONS: The cutoff point of at
      least 2 pathologically confirmed serrated lesions can serve as a screening tool
      for identifying patients meeting the World Health Organization criteria for
      serrated polyposis syndrome who would otherwise go undetected.

PMID- 24901686
TI  - Surgical outcomes in adults with benign and malignant sacrococcygeal teratoma: a
      single-institution experience of 26 cases.
AB  - BACKGROUND: Adult sacrococcygeal teratomas are rare, and limited data exist on
      their management and outcomes following surgery. OBJECTIVE: The aim of this study
      was to review the outcomes in adult patients undergoing surgery for
      sacrococcygeal teratomas. DESIGN: A retrospective review of our prospectively
      maintained surgical pathology and tumor registries was conducted. SETTING: This
      study was conducted at the Mayo Clinic in Rochester. Information was collected on
      patients treated between 1980 and 2013. PATIENTS: A total of 26 patients with
      sacrococcygeal teratoma were identified (19 female), with a median age of 37.5
      years. Malignancy was seen in 5 patients. MAIN OUTCOME MEASURES: Data on
      demographics, clinical presentation, tumor pathology, adjuvant therapy, surgical
      approach, surgical margins, use of preoperative biopsy, radiological
      investigations, morbidity, mortality, and local recurrence was collected.
      Complications were assessed by using the Clavien-Dindo system of classification.
      RESULTS: Patients most commonly presented with pelvic pain (n = 16) and/or a
      palpable mass (n = 15). On radiology, 8 lesions were purely cystic, 14 were
      mixed, and 4 were solid; teratoma was suspected as a diagnosis in 8 patients.
      Preoperative biopsy (13 patients) had 100% concordance with final pathology.
      Median tumor size was 6 cm, and the surgical approach was posterior only (n =
      15), anterior only (n = 5), and combined anterior-posterior (n = 6). Of 5
      patients with malignancy, 3 died of recurrent disease. LIMITATIONS: Limitations
      of this study include the small number of patients, the long study period, and
      the heterogeneous nature of these tumors. CONCLUSION: Presacral teratomas require
      multidisciplinary management and have a risk of malignant transformation. They
      are more common in females, and the majority are intrapelvic in location in
      adults. We recommend clinical evaluation, radiological investigation, and image
      guided biopsy in all suspicious presacral lesions. A treatment algorithm has been
      designed to improve the management of these rare tumors.

PMID- 24901687
TI  - Postoperative complications after cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy affect long-term outcome of patients with peritoneal
      metastases from colorectal cancer: a two-center study of 101 patients.
AB  - BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
      is an effective but potentially morbid treatment for colorectal cancer peritoneal
      metastases. The impact of treatment-related morbidity on long-term survival has
      been reported in various malignancies, but it has never been assessed in this
      clinical setting. OBJECTIVE: The aim of this study was to assess the impact of
      major postoperative complications on oncological outcomes after cytoreduction and
      hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases.
      DESIGN: Two prospective databases were reviewed. Major complications were defined
      as grade 3 to 5 according to the National Cancer Institute Common Terminology
      Criteria for Adverse Events version 3.0. The extent of peritoneal involvement was
      scored by the use of the Peritoneal Cancer Index. SETTINGS: This study was
      conducted in 2 high-volume peritoneal malignancy management centers. PATIENTS:
      One hundred one consecutive patients with peritoneal metastases potentially
      amenable to macroscopically complete cytoreduction were selected. INTERVENTIONS:
      Peritonectomy procedures and multivisceral resections were used to remove all
      macroscopic tumor, and mitomycin-C plus cisplatin-based hyperthermic
      intraperitoneal chemotherapy was used to control microscopic residual disease.
      MAIN OUTCOME MEASURES: The primary outcomes measured were overall and disease
      specific survival. RESULTS: Mortality and major morbidity were 3.0%, and 23.8%.
      Median follow-up was 44.9 months (95% CI, 24.1-65.7). Five-year disease-specific
      survival was 14.3% for patients who experienced major complications and 52.3% for
      those who did not (p = 0.001). Five-year overall survival was 11.7% for patients
      who experienced major complications, and 58.8% for those who did not (p = 0.003).
      At multivariate analysis, major morbidity correlated to both worse overall and
      disease-specific survival, along with a Peritoneal Cancer Index >19, and
      suboptimal cytoreduction. Poor performance status correlated only to worse
      disease-specific survival, and liver metastases correlated to worse overall
      survival. Longer operative time (OR, 4.1; 95% CI, 1.3-12.6; p = 0.01) and
      Peritoneal Cancer Index >19 (OR, 2.6; 95% CI, 1.1-6.0; p = 0.02) were independent
      risk factors for major morbidity. LIMITATIONS: This study is limited by its
      observational design. CONCLUSIONS: The prevention of major complications, by
      refining surgical technique and patient selection, is crucial because it affects
      oncologic outcome.

PMID- 24901688
TI  - Laparoscopic colorectal resections: a simple predictor model and a stratification
      risk for conversion to open surgery.
AB  - BACKGROUND: The advantages associated with the laparoscopic approach are lost
      when conversion is required. Available predictive models have failed to show
      external validation. Body surface area is a recently described risk factor not
      included in these models. OBJECTIVE: The aim of this study was to develop a
      clinical rule including body surface area for predicting conversion in patients
      undergoing elective laparoscopic colorectal surgery. DESIGN: This was a
      prospective cohort study. SETTING: This study was conducted at a single large
      tertiary care institution. PATIENTS: Nine hundred sixteen patients (mean age,
      63.9; range, 14-91 years; 53.2% female) who underwent surgery between January
      2004 and August 2011 were identified from a prospective database. MAIN OUTCOME
      MEASURES: Conversion rate was analyzed related to age, sex, obesity, disease
      location (colon vs rectum), type of disease (neoplastic vs nonneoplastic),
      history of previous surgery, and body surface area. A predictive model for
      conversion was developed with the use of logistic regression to identify
      independently associated variables, and a simple clinical prediction rule was
      derived. Internal validation of the model was performed by using bootstrapping.
      RESULTS: The conversion rate was 9.9% (91/916). Rectal disease, large patient
      size, and male sex were independently associated with higher odds of conversion
      (OR, 2.28 95%CI, 1.47-3.46]), 1.88 [1.1-3.44], and 1.87 [1.04-3.24]). The
      prediction rule identified 3 risk groups: low risk (women and nonlarge males),
      average risk (large males with colon disease), and high risk (large males with
      rectal disease). Conversion rates among these groups were 5.7%, 11.3%, and 27.8%
      (p < 0.001). Compared with the low-risk group, ORs for average- and high-risk
      groups were 2.17 (1.30-3.62, p = 0.004) and 6.38 (3.57-11.4, p < 0.0001).
      LIMITATIONS: The study was limited by the lack of external validation.
      CONCLUSION: This predictive model, including body surface area, stratifies
      patients with different conversion risks and may help to inform patients, to
      select cases in the early learning curve, and to evaluate the standard of care.
      However, this prediction rule needs to be externally validated in other samples
      (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A137).

PMID- 24901689
TI  - Nonoperative management of perforated diverticulitis with extraluminal air is
      safe and effective in selected patients.
AB  - BACKGROUND: The optimal treatment for diverticulitis with extraluminal air is
      controversial. OBJECTIVE: The purpose of this research was to evaluate the safety
      and effectiveness of nonoperative treatment of acute diverticulitis with
      extraluminal air. DESIGN: This was a retrospective cohort. SETTINGS: The study
      was conducted at an academic teaching hospital functioning as both a tertiary and
      secondary care referral center. PATIENTS: All of the patients with CT-diagnosed
      acute perforated diverticulitis with extraluminal air from 2006 through 2010 were
      included in this study. INTERVENTIONS: Nonoperative treatment composed of
      intravenous antibiotics, bowel rest, and percutaneous drainage were the included
      interventions. MAIN OUTCOME MEASURES: The need for operative management and
      mortality were measured. RESULTS: A total of 132 patients underwent nonoperative
      treatment, whereas 48 patients were primarily operated on. Patients treated
      nonoperatively were divided into 3 groups on the basis of identified factors that
      independently predicted risk for failure: 1) patients with pericolic air (n = 82)
      without abscess had a 99% success rate with 0% mortality. 2) Patients with
      distant intraperitoneal air (n = 29) had a 62% success ratewith 0% mortality.
      Abundant distant intraperitoneal air and fluid in the fossa Douglas were
      identified as risk factors for failure. Patients without these risk factors had
      an 86% success rate with nonoperative management. 3) Patients with distant
      retroperitoneal air (n = 14) had a 43% success rate with 7% mortality.
      LIMITATIONS: Comparison of nonoperative versus operative treatment cannot be made
      because of the study's retrospective nature. CONCLUSIONS: Nonoperative treatment
      of acute diverticulitis with extraluminal air is safe and effective in patients
      with a small amount of distant intraperitoneal air or pericolic air without
      clinical signs of peritonitis.

PMID- 24901690
TI  - Should we consider topical silver nitrate irrigation as a definitive nonsurgical
      treatment for perianal fistula?
AB  - BACKGROUND: Surgery is currently the sole treatment modality for anal fistulas.
      However, surgery is associated with complications such as permanent incontinence,
      which reduces quality of life. OBJECTIVE: To determine the rate of complete
      clinical healing of anal fistulas after irrigation of the fistula tract with
      silver nitrate solution as a nonsurgical treatment. DESIGN: Prospective single
      arm study. SETTING: Tertiary university hospital PATIENTS: : Adult patients with
      symptomatic perianal fistula presenting between June 2012 and January 2013.
      INTERVENTION: Irrigation of the fistula tract with 1% silver nitrate solution.
      Irrigation was repeated every 2 weeks when necessary. MAIN OUTCOME MEASURES: The
      primary outcome measure was the rate of complete clinical healing. RESULTS: Fifty
      six consecutive patients with anal fistula were analyzed. Of those, 29 (52%) had
      complete clinical healing without recurrence for a median of 10 months. The
      median number of irrigations needed for complete clinical healing was 4 (1-10).
      The level of satisfaction was excellent in patients with complete clinical
      healing. The frequency of complaints was the only independent factor that had an
      impact on healing; patients with intermittent discharge had a significantly
      higher rate of complete clinical healing (67%) than those with continuous
      discharge (40%). There were no notable complications. LIMITATIONS: Short follow
      up, small sample size, and no comparisons. CONCLUSION: This study demonstrates
      that the application of silver nitrate solution often produces a favorable
      outcome in the treatment of anal fistula. This method may be considered as a
      first-line treatment for the disease because it is simple, performed on an
      outpatient basis, minimally invasive, and lacks the complications encountered
      with current conventional surgical modalities.

PMID- 24901691
TI  - The disappointing quality of published studies on operative techniques for
      rectovaginal fistulas: a blueprint for a prospective multi-institutional study.
AB  - BACKGROUND: Treatment of rectovaginal fistulas is difficult, and many surgical
      interventions have been developed. The best surgical intervention for the closure
      of these fistulas is still unclear. OBJECTIVE: A systematic review was performed
      reporting the outcomes of different surgical techniques for rectovaginal
      fistulas. DATA SOURCES: Medline (PubMed, Ovid), Embase (Ovid), and The Cochrane
      Library databases were searched for eligible articles as well as the references
      of these articles. STUDY SELECTION: Two independent reviewers analyzed the search
      results for eligible articles based on title, abstract, and described results.
      INTERVENTION(S): Any surgical intervention for the closure of rectovaginal
      fistulas was included. MAIN OUTCOME MEASURES: The main outcome was closure rate.
      Secondary outcomes were quality of life, morbidity, and the effect on sexual
      functioning. RESULTS: Many articles with different operative techniques were
      identified and classified in the following categories: advancement flaps
      (endorectal and endovaginal), transperineal closure, Martius procedure, gracilis
      muscle transposition, rectal resections, transabdominal closure, mesh repair,
      plugs, endoscopic repairs, closure with biomaterials, and miscellaneous
      techniques. Results vary widely with closure rates between 0% and >80%. None of
      the studies were randomized. Because of the poor quality of the identified
      studies, the comparison of results and performance of a meta-analysis were not
      possible.Data regarding the secondary outcomes were mostly unavailable.
      LIMITATIONS: The major limitation of this review was the limited availability of
      high-quality prospective studies, making it impossible to perform a meta
      analysis. CONCLUSIONS: No conclusion about the best surgical intervention for
      rectovaginal fistulas could be formulated. More large studies of high quality are
      needed to find the best treatment for rectovaginal fistulas. A design for these
      high-quality studies was formulated.

PMID- 24901692
TI  - Transanal minimally invasive surgery for repair of rectourethral fistula.

PMID- 24901693
TI  - Laparoscopic local excision and rectoanal anastomosis for rectal gastrointestinal
      stromal tumor: modified laparoscopic intersphincteric resection technique.
AB  - BACKGROUND: Rectal GI stromal tumor is uncommon. Local excision with free
      resection margins provides adequate treatment, but extended surgery such as
      abdominoperineal resection has been frequently performed because of technical
      difficulties in the confined pelvic space. OBJECTIVE: We aimed to report the
      technical details of a new method of local excision for rectal GI stromal tumor:
      the modified laparoscopic intersphincteric resection technique. DESIGN: This
      study was a retrospective analysis. SETTING: This study was performed at a single
      institute. PATIENTS: We included 3 patients with rectal GI stromal tumor who
      underwent this procedure following neoadjuvant imatinib therapy. INTERVENTION:
      Medial-to-lateral retroperitoneal dissection was begun near the sacral
      promontory, and rectal dissection while preserving autonomic nerves was performed
      down to the pelvic floor into the anal canal without dividing the inferior
      mesenteric artery. Dissection between the tumor and prostate was meticulously
      performed under laparoscopic magnified view. Next, circumferential connection
      between the laparoscopic and transanal dissections was performed through a
      transanal approach, and the rectum was extracted through the anus. Circular full
      thickness local excision of the rectum and handsewn straight rectoanal
      anastomosis was performed. MAIN OUTCOME MEASURES: The safety and feasibility of
      this procedure were the primary outcomes measured by this study. RESULTS: The
      median operative time was 180 minutes, and the median estimated blood loss was
      115 mL. There were no conversions or intraoperative complications, and there was
      1 postoperative intestinal obstruction that recovered with conservative therapy.
      All patients had negative resection margins (R0), including 1 pathological
      complete response. LIMITATIONS: The study was limited by the small number of
      patients. CONCLUSIONS: This modified laparoscopic intersphincteric resection
      technique is a novel and safe method for local excision of rectal GI stromal
      tumors located very close to the anus (see Video, Supplemental Digital Content 1,
      http://links.lww.com/DCR/A139).

PMID- 24901696
TI  - Cultures of trust: effects of avatar faces and reputation scores on German and
      Arab players in an online trust-game.
AB  - Reputation systems as well as seller depictions (photos; avatars) have been shown
      to reduce buyer uncertainty and to foster trust in online trading. With the
      emergence of globalized e-markets, it remains an urgent question whether these
      mechanisms, found to be effective for Western cultures, also apply to other
      cultures. Hypothesizing that members of collectivistic cultures in contrast to
      those of individualistic cultures would rely more on visual social cues (seller
      faces) than on factual information (reputation scores), we compared buying
      decisions of Arab and German participants in an experimental trust game. Photo
      realistic avatars were used instead of photos to control facial features and
      expressions. The results revealed significant main effects for both reputation
      scores and avatar faces. Moreover, both variables significantly affected the
      purchase behavior of Arab as well as German buyers, suggesting cross-cultural
      universals in the processing of trust cues. The results have implications for
      future cross-cultural studies in e-commerce as well as the design of online
      markets and shared virtual environments. 

PMID- 24901698
TI  - Effects of litter manipulation on litter decomposition in a successional
      gradients of tropical forests in southern China.
AB  - Global changes such as increasing CO2, rising temperature, and land-use change
      are likely to drive shifts in litter inputs to forest floors, but the effects of
      such changes on litter decomposition remain largely unknown. We initiated a
      litter manipulation experiment to test the response of litter decomposition to
      litter removal/addition in three successional forests in southern China, namely
      masson pine forest (MPF), mixed coniferous and broadleaved forest (MF) and
      monsoon evergreen broadleaved forest (MEBF). Results showed that litter removal
      decreased litter decomposition rates by 27%, 10% and 8% and litter addition
      increased litter decomposition rates by 55%, 36% and 14% in MEBF, MF and MPF,
      respectively. The magnitudes of changes in litter decomposition were more
      significant in MEBF forest and less significant in MF, but not significant in
      MPF. Our results suggest that change in litter quantity can affect litter
      decomposition, and this impact may become stronger with forest succession in
      tropical forest ecosystem. 

PMID- 24901697
TI  - Deep evolutionary comparison of gene expression identifies parallel recruitment
      of trans-factors in two independent origins of C4 photosynthesis.
AB  - With at least 60 independent origins spanning monocotyledons and dicotyledons,
      the C4 photosynthetic pathway represents one of the most remarkable examples of
      convergent evolution. The recurrent evolution of this highly complex trait
      involving alterations to leaf anatomy, cell biology and biochemistry allows an
      increase in productivity by ~ 50% in tropical and subtropical areas. The extent
      to which separate lineages of C4 plants use the same genetic networks to maintain
      C4 photosynthesis is unknown. We developed a new informatics framework to enable
      deep evolutionary comparison of gene expression in species lacking reference
      genomes. We exploited this to compare gene expression in species representing two
      independent C4 lineages (Cleome gynandra and Zea mays) whose last common ancestor
      diverged ~ 140 million years ago. We define a cohort of 3,335 genes that
      represent conserved components of leaf and photosynthetic development in these
      species. Furthermore, we show that genes encoding proteins of the C4 cycle are
      recruited into networks defined by photosynthesis-related genes. Despite the wide
      evolutionary separation and independent origins of the C4 phenotype, we report
      that these species use homologous transcription factors to both induce C4
      photosynthesis and to maintain the cell specific gene expression required for the
      pathway to operate. We define a core molecular signature associated with leaf and
      photosynthetic maturation that is likely shared by angiosperm species derived
      from the last common ancestor of the monocotyledons and dicotyledons. We show
      that deep evolutionary comparisons of gene expression can reveal novel insight
      into the molecular convergence of highly complex phenotypes and that parallel
      evolution of trans-factors underpins the repeated appearance of C4
      photosynthesis. Thus, exploitation of extant natural variation associated with
      complex traits can be used to identify regulators. Moreover, the transcription
      factors that are shared by independent C4 lineages are key targets for
      engineering the C4 pathway into C3 crops such as rice.

PMID- 24901700
TI  - Effects of long chain fatty acid synthesis and associated gene expression in
      microalga Tetraselmis sp.
AB  - With the depletion of global fish stocks, caused by high demand and effective
      fishing techniques, alternative sources for long chain omega-3 fatty acids are
      required for human nutrition and aquaculture feeds. Recent research has focused
      on land-based cultivation of microalgae, the primary producers of omega-3 fatty
      acids in the marine food web. The effect of salinity on fatty acids and related
      gene expression was studied in the model marine microalga, Tetraselmis sp. M8.
      Correlations were found for specific fatty acid biosynthesis and gene expression
      according to salinity and the growth phase. Low salinity was found to increase
      the conversion of C18:4 stearidonic acid (SDA) to C20:4 eicosatetraenoic acid
      (ETA), correlating with increased transcript abundance of the Delta-6-elongase
      encoding gene in salinities of 5 and 10 ppt compared to higher salinity levels.
      The expression of the gene encoding beta-ketoacyl-coenzyme was also found to
      increase at lower salinities during the nutrient deprivation phase (Day 4), but
      decreased with further nutrient stress. Nutrient deprivation also triggered fatty
      acids synthesis at all salinities, and C20:5 eicosapentaenoic acid (EPA)
      increased relative to total fatty acids, with nutrient starvation achieving a
      maximum of 7% EPA at Day 6 at a salinity of 40 ppt. 

PMID- 24901701
TI  - Potent cytotoxic peptides from the Australian marine sponge Pipestela candelabra.
AB  - Two consecutive prefractionated fractions of the Australian marine sponge
      extract, Pipestela candelabra, were identified to be selectively active on the
      human prostate cancer cells (PC3) compared to the human neonatal foreskin
      fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in
      which four compounds are new small peptides. Their structures were characterized
      by spectroscopic and chemical analysis. These compounds inhibited selectively the
      growth of prostate cancer cells with IC50 values in the picomolar to sub
      micromolar range. Structure-activity relationship of these compounds is
      discussed. 

PMID- 24901702
TI  - Combining environment-driven adaptation and task-driven optimisation in
      evolutionary robotics.
AB  - Embodied evolutionary robotics is a sub-field of evolutionary robotics that
      employs evolutionary algorithms on the robotic hardware itself, during the
      operational period, i.e., in an on-line fashion. This enables robotic systems
      that continuously adapt, and are therefore capable of (re-)adjusting themselves
      to previously unknown or dynamically changing conditions autonomously, without
      human oversight. This paper addresses one of the major challenges that such
      systems face, viz. that the robots must satisfy two sets of requirements.
      Firstly, they must continue to operate reliably in their environment (viability),
      and secondly they must competently perform user-specified tasks (usefulness). The
      solution we propose exploits the fact that evolutionary methods have two basic
      selection mechanisms-survivor selection and parent selection. This allows
      evolution to tackle the two sets of requirements separately: survivor selection
      is driven by the environment and parent selection is based on task-performance.
      This idea is elaborated in the Multi-Objective aNd open-Ended Evolution (monee)
      framework, which we experimentally validate. Experiments with robotic swarms of
      100 simulated e-pucks show that monee does indeed promote task-driven behaviour
      without compromising environmental adaptation. We also investigate an extension
      of the parent selection process with a 'market mechanism' that can ensure
      equitable distribution of effort over multiple tasks, a particularly pressing
      issue if the environment promotes specialisation in single tasks. 

PMID- 24901703
TI  - beta-adrenergic receptor-dependent alterations in murine cardiac transcript
      expression are differentially regulated by gefitinib in vivo.
AB  - beta-adrenergic receptor (betaAR)-mediated transactivation of epidermal growth
      factor receptor (EGFR) has been shown to promote cardioprotection in a mouse
      model of heart failure and we recently showed that this mechanism leads to
      enhanced cell survival in part via regulation of apoptotic transcript expression
      in isolated primary rat neonatal cardiomyocytes. Thus, we hypothesized that this
      process could regulate cardiac transcript expression in vivo. To comprehensively
      assess cardiac transcript alterations in response to acute betaAR-dependent EGFR
      transactivation, we performed whole transcriptome analysis of hearts from C57BL/6
      mice given i.p. injections of the betaAR agonist isoproterenol in the presence or
      absence of the EGFR antagonist gefitinib for 1 hour. Total cardiac RNA from each
      treatment group underwent transcriptome analysis, revealing a substantial number
      of transcripts regulated by each treatment. Gefitinib alone significantly altered
      the expression of 405 transcripts, while isoproterenol either alone or in
      conjunction with gefitinib significantly altered 493 and 698 distinct
      transcripts, respectively. Further statistical analysis was performed, confirming
      473 transcripts whose regulation by isoproterenol were significantly altered by
      gefitinib (isoproterenol-induced up/downregulation antagonized/promoted by
      gefinitib), including several known to be involved in the regulation of numerous
      processes including cell death and survival. Thus, betaAR-dependent regulation of
      cardiac transcript expression in vivo can be modulated by the EGFR antagonist
      gefitinib. 

PMID- 24901704
TI  - Association of cross-reactive antibodies targeting peptidyl-arginine deiminase 3
      and 4 with rheumatoid arthritis-associated interstitial lung disease.
AB  - BACKGROUND: A subset of rheumatoid arthritis (RA) patients have detectable
      antibodies directed against the peptidyl-arginine deiminase (PAD) enzyme isoforms
      3 and 4. Anti-PAD3/4 cross-reactive antibodies (anti-PAD3/4XR) have been shown to
      lower the calcium threshold required for PAD4 activation, an effect potentially
      relevant to the pathogenesis of RA-associated interstitial lung disease (ILD).
      METHODS: RA patients underwent multi-detector computed tomography (MDCT) of the
      chest with interpretation by a pulmonary radiologist for ILD features. A semi
      quantitative ILD Score (range 0-32) was calculated. Concurrent serum samples were
      assessed for antibodies against PAD by immunoprecipitation with radiolabeled PAD3
      and PAD4. RESULTS: Among the 176 RA patients studied, any ILD was observed in 58
      (33%) and anti-PAD3/4XR was detected in 19 (11%). The frequency of any ILD among
      those with anti-PAD3/4XR was 68% vs. 29% among those with no anti-PAD (crude OR =
      5.39; p = 0.002) and vs. 27% among those with anti-PAD4 that was not cross
      reactive with PAD3 (crude OR = 5.74; p = 0.001). Both associations were stronger
      after adjustment for relevant confounders (adjusted ORs = 7.22 and 6.61,
      respectively; both p-values<0.01). Among ever smokers with anti-PAD3/4XR, the
      adjusted frequency of any ILD was 93% vs. 17% for never smokers without the
      antibody (adjusted OR = 61.4; p = 0.001, p-value for the interaction of smoking
      with anti-PAD3/4XR<0.05). CONCLUSIONS: The prevalence and extent of ILD was
      markedly higher among RA patients with anti-PAD3/4 cross-reactive antibodies,
      even after accounting for relevant confounders, particularly among ever smokers.
      These findings may suggest etiopathologic mechanisms of RA-ILD, and their
      clinical utility for predicting ILD warrants additional study.

PMID- 24901707
TI  - Two-dimensional 3d-4f heterometallic coordination polymers: syntheses, crystal
      structures, and magnetic properties of six new Co(II)-Ln(III) compounds.
AB  - Six new heterometallic cobalt(II)-lanthanide(III) complexes of formulas
      [Ln(bta)(H2O)2]2[Co(H2O)6].10H2O [Ln = Nd(III) (1) and Eu(III) (2)] and
      [Ln2Co(bta)2(H2O)8]n.6nH2O [Ln = Eu(III) (3), Sm(III) (4), Gd(III) (5), and
      Tb(III) (6)] (H4bta = 1,2,4,5-benzenetretracaboxylic acid) have been synthesized
      and characterized via single-crystal X-ray diffraction. 1 and 2 are isostructural
      compounds with a structure composed of anionic layers of [Ln(bta)(H2O)2]n(n-)
      sandwiching mononuclear [Co(H2O)6](2+) cations plus crystallization water
      molecules, which are interlinked by electrostatic forces and hydrogen bonds,
      leading to a supramolecular three-dimensional network. 3-6 are also isostructural
      compounds, and their structure consists of neutral layers of formula
      [Ln2Co(bta)2(H2O)8]n and crystallization water molecules, which are connected
      through hydrogen bonds to afford a supramolecular three-dimensional network.
      Heterometallic chains formed by the regular alternation of two nine-coordinate
      lanthanide(III) polyhedra [Ln(III)O9] and one compressed cobalt(II) octahedron
      [Co(II)O6] along the crystallographic c-axis are cross-linked by bta ligands
      within each layer of 3-6. Magnetic susceptibility measurements on polycrystalline
      samples for 3-6 have been carried out in the temperature range of 2.0-300 K. The
      magnetic behavior of these types of Ln(III)-Co(II) complexes, which have been
      modeled by using matrix dagonalization techniques, reveals the lack of magnetic
      coupling for 3 and 4, and the occurrence of weak antiferromagnetic interactions
      within the Gd(III)-Gd(III) (5) and Tb(III)-Tb(III) (6) dinuclear units through
      the exchange pathway provided by the double oxo(carboxylate) and double syn-syn
      carboxylate bridges. 

PMID- 24901705
TI  - Transcriptomic evidence for a dramatic functional transition of the malpighian
      tubules after a blood meal in the Asian tiger mosquito Aedes albopictus.
AB  - BACKGROUND: The consumption of a vertebrate blood meal by adult female mosquitoes
      is necessary for their reproduction, but it also presents significant
      physiological challenges to mosquito osmoregulation and metabolism. The renal
      (Malpighian) tubules of mosquitoes play critical roles in the initial processing
      of the blood meal by excreting excess water and salts that are ingested. However,
      it is unclear how the tubules contribute to the metabolism and excretion of
      wastes (e.g., heme, ammonia) produced during the digestion of blood.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we used RNA-Seq to examine global changes in
      transcript expression in the Malpighian tubules of the highly-invasive Asian
      tiger mosquito Aedes albopictus during the first 24 h after consuming a blood
      meal. We found progressive, global changes in the transcriptome of the Malpighian
      tubules isolated from mosquitoes at 3 h, 12 h, and 24 h after a blood meal.
      Notably, a DAVID functional cluster analysis of the differentially-expressed
      transcripts revealed 1) a down-regulation of transcripts associated with
      oxidative metabolism, active transport, and mRNA translation, and 2) an up
      regulation of transcripts associated with antioxidants and detoxification,
      proteolytic activity, amino-acid metabolism, and cytoskeletal dynamics.
      CONCLUSIONS/SIGNIFICANCE: The results suggest that blood feeding elicits a
      functional transition of the epithelium from one specializing in active
      transepithelial fluid secretion (e.g., diuresis) to one specializing in
      detoxification and metabolic waste excretion. Our findings provide the first
      insights into the putative roles of mosquito Malpighian tubules in the chronic
      processing of blood meals.

PMID- 24901706
TI  - Epidemiology of leptospira transmitted by rodents in southeast Asia.
AB  - BACKGROUND: Leptospirosis is the most common bacterial zoonoses and has been
      identified as an important emerging global public health problem in Southeast
      Asia. Rodents are important reservoirs for human leptospirosis, but
      epidemiological data is lacking. METHODOLOGY/PRINCIPAL FINDINGS: We sampled
      rodents living in different habitats from seven localities distributed across
      Southeast Asia (Thailand, Lao PDR and Cambodia), between 2009 to 2010. Human
      isolates were also obtained from localities close to where rodents were sampled.
      The prevalence of Leptospira infection was assessed by real-time PCR using DNA
      extracted from rodent kidneys, targeting the lipL32 gene. Sequencing rrs and secY
      genes, and Multi Locus Variable-number Tandem Repeat (VNTR) analyses were
      performed on DNA extracted from rat kidneys for Leptospira isolates molecular
      typing. Four species were detected in rodents, L. borgpetersenii (56% of positive
      samples), L. interrogans (36%), L. kirschneri (3%) and L. weilli (2%), which were
      identical to human isolates. Mean prevalence in rodents was approximately 7%, and
      largely varied across localities and habitats, but not between rodent species.
      The two most abundant Leptospira species displayed different habitat
      requirements: L. interrogans was linked to humid habitats (rice fields and
      forests) while L. borgpetersenii was abundant in both humid and dry habitats (non
      floodable lands). CONCLUSION/SIGNIFICANCE: L. interrogans and L. borgpetersenii
      species are widely distributed amongst rodent populations, and strain typing
      confirmed rodents as reservoirs for human leptospirosis. Differences in habitat
      requirements for L. interrogans and L. borgpetersenii supported differential
      transmission modes. In Southeast Asia, human infection risk is not only
      restricted to activities taking place in wetlands and rice fields as is commonly
      accepted, but should also include tasks such as forestry work, as well as the
      hunting and preparation of rodents for consumption, which deserve more attention
      in future epidemiological studies.

PMID- 24901708
TI  - Structural insights into SraP-mediated Staphylococcus aureus adhesion to host
      cells.
AB  - Staphylococcus aureus, a Gram-positive bacterium causes a number of devastating
      human diseases, such as infective endocarditis, osteomyelitis, septic arthritis
      and sepsis. S. aureus SraP, a surface-exposed serine-rich repeat glycoprotein
      (SRRP), is required for the pathogenesis of human infective endocarditis via its
      ligand-binding region (BR) adhering to human platelets. It remains unclear how
      SraP interacts with human host. Here we report the 2.05 A crystal structure of
      the BR of SraP, revealing an extended rod-like architecture of four discrete
      modules. The N-terminal legume lectin-like module specifically binds to N
      acetylneuraminic acid. The second module adopts a beta-grasp fold similar to Ig
      binding proteins, whereas the last two tandem repetitive modules resemble
      eukaryotic cadherins but differ in calcium coordination pattern. Under the
      conditions tested, small-angle X-ray scattering and molecular dynamic simulation
      indicated that the three C-terminal modules function as a relatively rigid stem
      to extend the N-terminal lectin module outwards. Structure-guided mutagenesis
      analyses, in addition to a recently identified trisaccharide ligand of SraP,
      enabled us to elucidate that SraP binding to sialylated receptors promotes S.
      aureus adhesion to and invasion into host epithelial cells. Our findings have
      thus provided novel structural and functional insights into the SraP-mediated
      host-pathogen interaction of S. aureus. 

PMID- 24901712
TI  - TAAR1 transforms thinking about a plant alkaloid that transformed the practice of
      medicine.

PMID- 24901711
TI  - Adaptor protein complexes AP-1 and AP-3 are required by the HHV-7 Immunoevasin
      U21 for rerouting of class I MHC molecules to the lysosomal compartment.
AB  - The human herpesvirus-7 (HHV-7) U21 gene product binds to class I major
      histocompatibility complex (MHC) molecules and reroutes them to a lysosomal
      compartment. Trafficking of integral membrane proteins to lysosomes is mediated
      through cytoplasmic sorting signals that recruit heterotetrameric clathrin
      adaptor protein (AP) complexes, which in turn mediate protein sorting in post
      Golgi vesicular transport. Since U21 can mediate rerouting of class I molecules
      to lysosomes even when lacking its cytoplasmic tail, we hypothesize the existence
      of a cellular protein that contains the lysosomal sorting information required to
      escort class I molecules to the lysosomal compartment. If such a protein exists,
      we expect that it might recruit clathrin adaptor protein complexes as a means of
      lysosomal sorting. Here we describe experiments demonstrating that the MU
      adaptins from AP-1 and AP-3 are involved in U21-mediated trafficking of class I
      molecules to lysosomes. These experiments support the idea that a cellular
      protein(s) is necessary for U21-mediated lysosomal sorting of class I molecules.
      We also examine the impact of transient versus chronic knockdown of these adaptor
      protein complexes, and show that the few remaining MU subunits in the cells are
      eventually able to reroute class I molecules to lysosomes. 

PMID- 24901714
TI  - Microwave-assisted coupling reaction of N-aryl sydnones with 2
      nitromethylenethiazolidine: unexpected formation of (Z)-2-(nitro((E)-p
      substitutedphenyldiazenyl)methylene)thiazolidines.
AB  - Reaction of N-aryl sydnones with 2-nitromethylenethiazolidine straightforwardly
      gives rise to the formation of (Z)-2-(nitro((E)-p
      substitutedphenyldiazenyl)methylene)thiazolidines in xylene and dimethoxyethane
      under microwave irradiation. A meaningful and plausible mechanism for this
      transformation is proposed, which anticipates the extrusion of an aceto-lactone
      like moiety before a coupling occurs. The structures of all the new compounds
      were identified on the basis of the data obtained from the NMR, IR, X-ray
      diffraction spectra, HRMS measurements, and physical characteristics. 

PMID- 24901709
TI  - Disruption of interleukin-1beta autocrine signaling rescues complex I activity
      and improves ROS levels in immortalized epithelial cells with impaired cystic
      fibrosis transmembrane conductance regulator (CFTR) function.
AB  - Patients with cystic fibrosis (CF) have elevated concentration of cytokines in
      sputum and a general inflammatory condition. In addition, CF cells in culture
      produce diverse cytokines in excess, including IL-1beta. We have previously shown
      that IL-1beta, at low doses (~30 pM), can stimulate the expression of CFTR in T84
      colon carcinoma cells, through NF-kappaB signaling. However, at higher doses
      (>2.5 ng/ml, ~150 pM), IL-1beta inhibit CFTR mRNA expression. On the other hand,
      by using differential display, we found two genes with reduced expression in CF
      cells, corresponding to the mitochondrial proteins CISD1 and MTND4. The last is a
      key subunit for the activity of mitochondrial Complex I (mCx-I); accordingly, we
      later found a reduced mCx-I activity in CF cells. Here we found that IB3-1 cells
      (CF cells), cultured in serum-free media, secrete 323+/-5 pg/ml of IL-1beta in 24
      h vs 127+/-3 pg/ml for S9 cells (CFTR-corrected IB3-1 cells). Externally added IL
      1beta (5 ng/ml) reduces the mCx-I activity and increases the mitochondrial
      (MitoSOX probe) and cellular (DCFH-DA probe) ROS levels of S9 (CFTR-corrected IB3
      1 CF cells) or Caco-2/pRSctrl cells (shRNA control cells) to values comparable to
      those of IB3-1 or Caco-2/pRS26 cells (shRNA specific for CFTR). Treatments of IB3
      1 or Caco-2/pRS26 cells with either IL-1beta blocking antibody, IL-1 receptor
      antagonist, IKK inhibitor III (NF-kappaB pathway) or SB203580 (p38 MAPK pathway),
      restored the mCx-I activity. In addition, in IB3-1 or Caco-2/pRS26 cells, IL
      1beta blocking antibody, IKK inhibitor III or SB203580 reduced the mitochondrial
      ROS levels by ~50% and the cellular ROS levels near to basal values. The AP-1
      inhibitors U0126 (MEK1/2) or SP600125 (JNK1/2/3 inhibitor) had no effects. The
      results suggest that in these cells IL-1beta, through an autocrine effect, acts
      as a bridge connecting the CFTR with the mCx-I activity and the ROS levels. 

PMID- 24901715
TI  - 2-Aroylindoles from o-bromochalcones via Cu(I)-catalyzed S(N)Ar with an azide and
      intramolecular nitrene C-H insertion.
AB  - A simple procedure for the synthesis of 2-aroylindole derivatives comprising a
      one-pot CuI-catalyzed SNAr reaction of o-bromochalcones with sodium azide and
      subsequent intramolecular cyclization through nitrene C-H insertion has been
      developed. This protocol is also applicable with the 2'-bromocinnamates giving
      the indole-2-carboxylates. 

PMID- 24901713
TI  - Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to
      doxorubicin by downregulation of MDR-1 expression.
AB  - Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein
      (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy
      for colorectal cancer. Previous studies have indicated that sinomenine can
      enhance the absorption of various P-gp substrates. In the present study, we
      investigated the effect of sinomenine on the chemoresistance in colon cancer
      cells and explored the underlying mechanism. We developed multidrug-resistant
      Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing
      concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1
      genes as well as activation of the NF-kappaB signal pathway in MDR-Caco-2 cells.
      Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2
      cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through
      inhibition of the NF-kappaB signaling pathway. These findings provide a new
      potential strategy for the reversal of P-gp-mediated anticancer drug resistance. 

PMID- 24901716
TI  - C3HC4-type RING finger protein NbZFP1 is involved in growth and fruit development
      in Nicotiana benthamiana.
AB  - C3HC4-type RING finger proteins constitute a large family in the plant kingdom
      and play important roles in various physiological processes of plant life. In
      this study, a C3HC4-type zinc finger gene was isolated from Nicotiana
      benthamiana. Sequence analysis indicated that the gene encodes a 24-kDa protein
      with 191 amino acids containing one typical C3HC4-type zinc finger domain; this
      gene was named NbZFP1. Transient expression of pGDG-NbZFP1 demonstrated that
      NbZFP1 was localized to the chloroplast, especially in the chloroplasts of cells
      surrounding leaf stomata. Virus-induced gene silencing (VIGS) analysis indicated
      that silencing of NbZFP1 hampered fruit development, although the height of the
      plants was normal. An overexpression construct was then designed and transferred
      into Nicotiana benthamiana, and PCR and Southern blot showed that the NbZFP1 gene
      was successfully integrated into the Nicotiana benthamiana genome. The transgenic
      lines showed typical compactness, with a short internode length and sturdy stems.
      This is the first report describing the function of a C3HC4-type RING finger
      protein in tobacco. 

PMID- 24901717
TI  - Effect of eicosapentaenoic acid on the expression of ABCG1 gene in the human
      monocyte THP-1 cells.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disability in
      developed countries. Atherosclerosis is the major cause of CVD, accounting for
      about half of the attributed deaths. Cholesterol homeostasis is one of the most
      important factors in atherosclerosis. ATP-Binding cassette transporters
      cholesterol. Omega (omega) 3 fatty acids are important ligands for regulation of
      ABC transporters such as ABCG1. Concern has been raised that the low absolute
      intakes of EPA and high ratios of omega-6 polyunsaturated fatty acids (omega-6
      PUFA) to EPA may predispose some individuals to CVD. Eicosapentaenoic acid (EPA)
      is the most abundant omega3 fatty acid in the diet. The objective of this study
      was to evaluate the effect of different concentrations of EPA on the expression
      of ABCG1 gene in the human monocyte THP-1 cells. In this study, THP-1 cells were
      cultured in RPMI 1640 medium, THP-1 monocytes were then differentiated to
      macrophages with PMA (phorbol myristic acid) and stimulated with 50, 75 and 100
      MUM of EPA for 24 h at 37 degrees C. We examined the effects of EPA treatment on
      the expression of ABCG1 gene using Quantitative Real time RT-PCR (qRT-PCR). Our
      results, indicate that ABCG1 mRNA expression was significantly reduced by 50, 75
      and 100 MUM EPA fatty acid treatments as compared to the control cells (r =
      0.009, r < 0.001 and r = 0.002, respectively). These results suggest that
      polyunsaturated fatty acids (PUFAs) such as EPA have an effect on the cholesterol
      homeostasis in macrophages, and they can change the expression of ABCG1 gene. It
      seems that EPA has different effects on gene expression and lipid metabolism. 

PMID- 24901718
TI  - Evaluation of antimicrobial resistance pattern of nosocomial and community
      bacterial pathogens at a teaching hospital in Tehran,Iran.
AB  - Antimicrobial resistance in pathogens not only in hospitals but also in the
      community has become an important public health problem. The aim of this study
      was to determine the antimicrobial resistance patterns of predominant pathogens
      from hospitalized and outpatients in a university hospital in Tehran, Iran. A
      total of 820 samples of common Gram-negative and Gram-positive bacteria were
      collected from a major referral and teaching hospital affiliated to Tehran
      University of Medical Sciences in Iran during April 2010 to February 2011. The
      pattern of antibiotic resistance was determined by disk diffusion test as
      recommended by the Clinical Laboratory and Standards Institute (CLSI). Gram
      negative bacilli were the most isolated pathogens. Acinetobacter spp. and
      Pseudomonas aeruginosa (P. aeruginosa) was the most antibiotic-resistant
      pathogens. Imipenem and piperacillin/tazobactam were the most active
      antimicrobials against gram-negative bacilli whereas vancomycin was the
      antimicrobial agent most consistently active against the Gram-positive cocci.
      Community-acquired organisms were more susceptible to antimicrobial drugs tested
      than nosocomial isolates. The rates of antibiotic resistance among isolated
      pathogens in this study were approximately similar to other studies. However,
      high rates of antibiotic resistance among Acinetobacter spp and P. aeruginosa,
      the most isolated pathogens, indicating that antibiotic policy is urgently needed
      to prevent the resistance development ago. 

PMID- 24901719
TI  - Sequences type analysis of Candida albicans isolates from Iranian human
      immunodeficiency virus infected patients with oral candidiasis.
AB  - The growing number of immunocompromised individuals has increased the incidence
      of infections caused by Candida species during the recent decades. Typing of C.
      albicans on the basis of DNA sequences at multiple loci has greatly advanced our
      knowledge about the epidemiology and phylogeny of candidiasis. The aim of this
      study was to evaluate the diversity, and genetic relationships among C. albicans
      isolates obtained from HIV patients in Iran. using multilocus sequence typing
      (MLST) method. We analyzed 25 C. albicans isolates obtained from HIV positive
      patients referred to Iranian Research Center for HIV/AIDS. After diagnostic test
      and DNA extraction C. albicans isolates were typed using the original MLST scheme
      explained previously include of six loci: ACC1, VPS13, GLN4, ADP1, RPN2, and
      SYA1. Fifty one (2.17%) nucleotide sites were found to be polymorphic; all were
      found to be heterozygous in at least one isolate. For the 25 clinical isolates,
      22 diploid sequence types were defined by the genotypes identified from the six
      loci. The MLST data suggest a relatively high level of divergence in the
      population structure of C. albicans isolated from HIV infected patients. These
      findings indicate that in these patients there is a favorable context for the
      growth of potential pathogenic C. albicans. We found no association between
      fluconazole resistance, highly active antiretroviral therapy (HAART) receiving
      and either sequence type or group. 

PMID- 24901720
TI  - Influence of body mass indexes on response to treatment in acute asthma.
AB  - Increases in body mass index (BMI) are reported to influence asthma response to
      treatment. The aim of this study was to investigate the relationship between BMI
      and response to treatment in a group of patients that were referred for asthma
      control. Effectiveness measurements in this analysis included percentage of
      changes in forced volume in 1 second (FEV1), forced volume capacity (FVC),
      FEV1/FVC, and forced expiratory flow between 25% and 75% of FVC (FEF25-75%). A
      total of 293 subjects with asthma of both genders and above 18 years of age were
      divided into the following BMI categories: 107 (36.5%) non-obese (BMI < 25), 186
      (63.5%) overweight and obese (BMI >= 25). Percentage of change was defined as
      change in variable between baseline and end-of-treatment. Analyses of non-obese
      vs. overweight/obese asthmatics demonstrated non-significant differences in
      baseline FEV1 (1.62 +/- 0.56 Lit vs. 1.63 +/- 0.56 Lit L, P = 0.89); FVC (2.58 +/
      0.73 Lit vs. 2.47 +/- 0.82 Lit, P = 0.25); and FEF25-75% (1.04 +/- 0.55 ml/sec
      vs. 1.05 +/- 0.50 ml/sec, P = 0.47) respectively. Compared with non-obese
      subjects, in overweight/obese subjects with asthma were less responded to
      treatment. Percentage changes of FEV1, FVC, FEF25-75%, and FEV1/FVC in non-obese
      versus obese/overweight patients were: 79.57 +/- 55.14 % vs. 62.13 +/- 41.72%, P
      = 0.005; 47.71 +/- 33.76% vs. 39.93 +/- 28.30%, P = 0.036; 151.98 +/- 127.82% vs.
      123 +/- 91.12%, P = 0.041; 20.54 +/- 15.63% vs. 15.63 +/- 11.32%, P = 0.005;
      respectively. Percentage changes of spirometric values to treatment in over
      weight/obese asthmatic patient were lesser in compared with non-obese subjects.

PMID- 24901721
TI  - Human papilloma virus and esophageal squamous cell carcinoma.
AB  - Human papillomavirus (HPV) has also been suggested as an etiology of esophageal
      squamous cell carcinoma (SCC). The aim of this study was to investigate the
      prevalence of HPV infection in esophageal SCCs in our region with strict
      contamination control to prevent false positive results. Thirty cases of
      esophageal squamous cell carcinomas were chosen by simple random selection in a
      period of two years. PCR for target sequence of HPV L1 gene was performed on
      nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue
      samples in both case and control groups were negative for HPV-DNA. Although the
      number of cases in this study was limited, the contribution of HPV in the
      substantial number of esophageal SCCs in our region is unlikely. 

PMID- 24901722
TI  - Evaluating the effect of four extracts of avocado fruit on esophageal squamous
      carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood
      mononuclear cells.
AB  - Most patients with gastrointestinal cancers refer to the health centers at
      advanced stages of the disease and conventional treatments are not significantly
      effective for these patients. Therefore, using modern therapeutic approaches with
      lower toxicity bring higher chance for successful treatment and reduced adverse
      effects in such patients. The aim of this study is to evaluate the effect of
      avocado fruit extracts on inhibition of the growth of cancer cells in comparison
      with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate,
      and petroleum extracts of avocado (Persea americana) fruit were prepared. Then,
      the effects if the extracts on the growth of esophageal squamous cell carcinoma
      and colon adenocarcinoma cell lines were evaluated in comparison with the control
      group using the MTT test in the cell culture medium. Effects of the four extracts
      of avocado fruit on three cells lines of peripheral blood mononuclear cells,
      esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The
      results showed that avocado fruit extract is effective in inhibition of cancer
      cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in
      phytochemicals, which play an important role in inhibition of growth of cancer
      cells. The current study for the first time demonstrates the anti-cancer effect
      of avocado fruit extracts on two cancers common in Iran. Therefore, it is
      suggested that the fruit extracts can be considered as appropriate complementary
      treatments in treatment of esophageal and colon cancers. 

PMID- 24901723
TI  - Risk of postoperative hypocalcemia in patients underwent total thyroidectomy,
      subtotal thyroidectomy and lobectomy surgeries.
AB  - The main objective of this study was to identify the incidence of post
      thyroidectomy hypocalcemia in patients underwent lobectomy, subtotal
      thyroidectomy or total thyroidectomy. This randomized trial study was performed
      from May 2010 to July 2011 among 108 consecutive patients undergoing
      thyroidectomy. Patients were allocated into 3 groups based on the 3 common type
      of thyroidectomy. Pre and postoperative serum calcium levels were determined by
      using standard protocol for all patients. All patients' preoperative serum
      calcium levels were normal. Post-thyroidectomy hypoglycemia occurred in 0%, 8.3%
      and 8.3% of patients who underwent total hypocalcemia, subtotal thyroidectomy and
      lobectomy, respectively, which represents 5.6% of all patients who shown
      hypocalcemia (P=0.58). Serum calcium levels were fall in 93% patients, however
      within several days were returned to normal ranges. We did not find a significant
      relation between the hypocalcemia and thyroidectomy types. We recommended
      determination other alternative factors as a more effective prediction for
      postoperative hypocalcemia. 

PMID- 24901724
TI  - Unfavorable survival rates in Iranian patients with gastric cancers: a single
      center experience from Tehran.
AB  - We examined the effect of potential interfering factors that play major roles in
      the outcome of our patients with stomach cancer. 100 consecutive patients
      diagnosed with gastric cancers were prospectively observed, treated and followed
      from November 2009 to January. Absence of Helicobacter pylori infection
      (P=0.027), absence of vascularisation (P<0.001), and undetermined
      histopathological type of adenocarcinoma (P=0.003) were factors significantly
      associated with higher grade of gastric lesions. Life tables were used to define
      survival of gastric cancers. Survival rates of these patients at 1st week, 1st
      month, 2nd month, 3rd month, and 6th month were 97%, 96%, 91%, 90%, and 82%,
      respectively. The only determinant of 6 months of survival was age over 68
      (P=0.039). Our study confirms our previous knowledge that gastric cancers have
      unfavorable outcome in Iran. 

PMID- 24901725
TI  - The effect of gamma irradiation on the osteoinductivity of demineralized human
      bone allograft.
AB  - The gamma irradiation has been used for end sterilization of allograft bones and
      its effects with a 25 kGy dosage on the osteoinductive properties of
      demineralized bone allograft powder was studied. This work carried out using an
      experimental method in an animal model. In this study the demineralized bone
      allograft powder which had been sterilized and prepared with gamma irradiation in
      a 25 kGy dosage in 18 hours, was used as a study group and the demineralized bone
      allograft powder which had been prepared aseptically was used as the reference
      group. 30 mg of bone powder from each group were implanted into right and left
      paravertebral muscles of eighteen rats, separately. After four weeks, the
      implanted samples were harvested with a 0.5 cm border and then the
      osteoinductivity of implants in two groups were compared with histopathologic
      studies. In 94.4% of the reference samples a new bone formation was observed. In
      the study group, this difference was observed only in 27.7% of samples (P<0.002).
      It appears that using gamma irradiation may lead to a reduction in osteoinduction
      properties of demineralized bone allograft powder. 

PMID- 24901726
TI  - Evaluation of elastic fibers pattern with orcein staining in differential
      diagnosis of lichen planopilaris and discoid lupus erythematosus.
AB  - Differential diagnosis of lichen planopilaris and discoid lupus erythematosus
      especially in late stages is a problem for clinicians and pathologists. Our aim
      was to find discriminator histopathologic findings that help us to achieve
      definite diagnosis without using immunofluorescence study. The histopathologic
      findings in 77 cases of lichen planopilaris were compared with those of 26 cases
      of discoid lupus erythematosus with Hematoxylin & Eosin and especially staining
      (Alcian blue pH 2.5, Periodic Acid Shiff, Orcein). Final histopathologic
      diagnosis was based on histologic findings, clinicopathological correlation, past
      medical history and immunofluorescence studies if were applied before. Then
      elastic fibers pattern in dermis and follicular sheath with orcein staining were
      described without having information about final diagnosis. New and subtle
      presentations of histologic changes were assessed. We compared all
      histopathologic finding for each staining method. Some histologic changes such as
      hypergranulosis, epidermal atrophy, mucin deposition, diffuse scar and some other
      patterns were not specific for any diagnosis. A setting of histopathologic
      findings and clinicopathological correlation were needed for accurate diagnosis.
      We had only one specimen for the vertical section, and we had no horizontal
      sections. Description of elastic fibers pattern in orcein staining may be helpful
      in achieving a specific diagnosis, but this is not completely reliable, and we
      had overlap features. Finally, immunofluorescence study may be recommended for
      suspicious cases. 

PMID- 24901727
TI  - Patellofemoral ligament reconstruction in a patient with Rubinstein-Taybi
      syndrome.
AB  - Recurrent dislocation of patella may occur in patients with ligament laxity.
      Method of treatment in this condition is controversial but patellofemoral
      ligament reconstruction is the most accepted method. We present a patient with
      Rubinstein-Taybi syndrome and recurrent patellar dislocation who managed
      successfully by patellofemoral ligament reconstruction. 

PMID- 24901728
TI  - Co-existence of cutaneous leishmaniasis with pleural effusion: a case report from
      Iran.
AB  - Herein, a 12-year-old Afghan boy with chronic cutaneous leishmaniasis on the face
      and verrucous lesions on the body and pleural effusion suspected of having co
      existent tuberculosis has been presented. The cutaneous lesions were appeared for
      five years before his admission. Leishman-Donovan bodies were seen in H&E
      (Hematoxylin and eosin) slide of skin lesion specimens. The pathogenic species
      was proved to be Leishmania tropica using Polymerase Chain Reaction (PCR) method.
      Purified Protein Derivative (PPD) and Leishmanin Skin Test (LST) were strongly
      positive. The patient was treated with systemic and intralesional meglumine
      antimoniate (Glucantime) for cutaneous leishmaniasis and then with anti
      tuberculosis drugs for pleural effusion. Afterwards, pleural effusion was
      disappeared and cutaneous leishmaniasis cured. 

PMID- 24901729
TI  - Pseudo-aneurysm of anterior tibia artery simulating a soft tissue sarcoma: a case
      report.
AB  - A pseudo aneurysm results from leakage of blood from an artery after trauma or
      dehiscence or separation of a surgical anastomosis. The reported rate of pseudo
      aneurysm in access sites range from 0.88% to 8%. It has some cause like
      penetrating trauma, blunt trauma and endovascular procedure. The differential
      diagnoses of this lesion are hematoma, AV fistula, lymphadenopathy, lymphocele,
      DVT, compartment syndrome, soft tissue tumor. A 16 years old male was referred to
      our clinic with progressive swelling in his right leg for the past three month.
      In primary survey (MRI, CT, Bone Scan) patient was diagnosed with soft tissue
      tumor, but after biopsy and angiography he was diagnosed with pseudo aneurysm of
      anterior tibialis artery. Despite easy diagnosis of p aneurysm in most cases, the
      signs and symptoms are more likely to soft tissue mass in rare cases. So pseudo
      aneurysm should always be considered as one differential diagnosis for soft
      tissue tumors. 

PMID- 24901730
TI  - Severe herpes zoster neuralgia in a pregnant woman treated with acetaminophen.
AB  - There is no recommendation for the treatment of herpes zoster neuralgia in
      pregnancy, as it even sometimes needs administration of strong opioids. MAIN
      OBSERVATION: Here, we report a pregnant woman with severe zoster neuralgia who
      responded favorably to acetaminophen. Due to the drug's safe profile and good
      efficacy, acetaminophen can be used as an alternative for herpetic neuralgia in
      pregnant women. However, controlled studies are still needed.

PMID- 24901732
TI  - Caring for patients with melanoma in the primary care setting.
AB  - The incidence of melanoma is steadily rising and mortality continues to increase.
      This article describes types of melanoma and the role of primary care providers
      in the long-term management and follow-up of patients diagnosed with melanoma. 

PMID- 24901731
TI  - An update on nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the accumulation of fat (steatosis)
      in the liver for reasons other than excess alcohol intake. The diagnosis of NAFLD
      is becoming more common for a number of reasons, including increased awareness
      among healthcare providers, improved diagnostic tools, and a greater prevalence
      of the disorder. This article provides primary care providers with the current
      understanding of NAFLD, including evidence-based recommendations for managing
      patients with this common condition. 

PMID- 24901733
TI  - Molecular simulation of the adsorption of methane in Engelhard titanosilicate
      frameworks.
AB  - Molecular simulations were carried out to elucidate the influence of structural
      heterogeneity and of the presence of extra-framework cations and water molecules
      on the adsorption of methane in Engelhard titanosilicates, ETS-10 and ETS-4. The
      simulations employed three different modeling approaches, (i) with fixed cations
      and water at their single crystal positions, (ii) with fixed cations and water at
      their optimized positions, and (iii) with mobile extra-framework cations and
      water molecules. Simulations employing the final two approaches provided a more
      realistic description of adsorption in these materials, and showed that at least
      some cations and water molecules are displaced from the crystallographic
      positions obtained from single crystal data. Upon methane adsorption in the case
      of ETS-10, the cations move to the large rings, while in the case of ETS-4, the
      water molecules and cations migrate to more available space in the larger 12
      membered ring channels for better accommodation of the methane molecules. For ETS
      4, we also considered adsorption in all possible pure polymorph structures and
      then combined these to provide an estimate of adsorption in a real ETS-4 sample.
      By comparing simulated adsorption isotherms to experimental data, we were able to
      show that both the mobility of extra-framework species and the structural
      heterogeneity should be taken into account for realistic predictions of
      adsorption in titanosilicate materials. 

PMID- 24901734
TI  - The HELIOS trial protocol: a phase III study of ibrutinib in combination with
      bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia.
AB  - Ibrutinib is an orally administered, covalent inhibitor of Bruton's tyrosine
      kinase with activity in B-cell malignancies based on Phase I/II studies. We
      describe the design and rationale for the Phase III HELIOS trial (trial
      registration: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745) investigating
      whether ibrutinib added to bendamustine and rituximab (BR) provides benefits over
      BR alone in patients with relapsed/refractory chronic lymphocytic leukemia/small
      lymphocytic lymphoma. Eligible patients must have relapsed/refractory disease
      measurable on CT scan and meet >= 1 International Workshop on Chronic Lymphocytic
      Leukemia criterion for requiring treatment; patients with del(17p) are excluded.
      All patients receive BR (maximum six cycles) as background therapy and are
      randomized 1:1 to placebo or ibrutinib 420 mg/day. Treatment with ibrutinib or
      placebo will start concomitantly with BR and continue until disease progression
      or unacceptable toxicity. The primary end point is progression-free survival.
      Secondary end points include safety, objective response rate, overall survival,
      rate of minimal residual disease-negative remissions, and patient-reported
      outcomes. Tumor response will be assessed using the International Workshop on
      Chronic Lymphocytic Leukemia guidelines.

PMID- 24901735
TI  - Healthcare reimbursement models and orthopaedic trauma: will there be change in
      patient management? A survey of orthopaedic surgeons.
AB  - OBJECTIVES: Healthcare reimbursement models are changing. Fee-for-service may be
      replaced by pay-for-performance or capitated care. The purpose of this study was
      to examine the potential changes in orthopaedic trauma surgery patient management
      based on potential shifts in policy surrounding readmission and reimbursement.
      METHODS: An e-mail survey consisting of 3 case-based scenarios was delivered to
      375 orthopaedic surgeons. Five options for management of each case were provided.
      Each of the 3 cases was presented in 3 different healthcare settings: scenario A,
      our current healthcare setting; scenario B, in which 90-day reoperation or
      readmission would not be reimbursed; and scenario C, in which a capitated
      healthcare structure paid a fixed amount per patient. RESULTS: The response rate
      was 40.3% with 151 surgeons completing the survey. A 71.1% of the respondents
      were in private practice settings, whereas 28.3% were in academic centers. In
      each case, there was significant increase in the respondents' choice to transfer
      patients to tertiary care centers under both the capitated and penalization
      systems as compared with the current fee-for-service model. CONCLUSIONS: This
      survey is the first of its kind to demonstrate through case-based scenarios that
      a healthcare system with readmission penalties and capitated reimbursement models
      may lead to a significant increase in transfer of complex orthopaedic trauma
      patients to tertiary care centers. Physicians should be encouraged to continue
      evidence-based medicine instead of making decisions due to finances, and other
      avenues of healthcare savings should be explored to decrease patient transfer
      rates with healthcare changes.

PMID- 24901736
TI  - Short-term prospective effects of impulsivity on binge drinking: mediation by
      positive and negative drinking consequences.
AB  - OBJECTIVE: Although the association of impulsivity with diverse alcohol outcomes
      has been documented, the mechanisms by which impulsivity predicts drinking over
      time remain to be fully characterized. The authors examined whether positive
      drinking consequences, but not negative drinking consequences, mediated the
      association between impulsivity and subsequent binge drinking, over and above
      prior binge drinking. PARTICIPANTS: Participants were 171 college students.
      METHODS: Participants completed 2 online surveys with an average interval of 68
      days between assessments at Time 1 (September to October 2012) and Time 2
      (November to December 2012). RESULTS: Path analysis showed that, among 5 facets
      of impulsivity, the effect of sensation seeking on subsequent binge drinking was
      completely mediated by prior positive consequences. No mediating effects of
      negative consequences were found. CONCLUSIONS: Prior experience of positive
      drinking consequences may serve as one of the risk pathways by which sensation
      seeking shapes binge drinking over time. Personalized intervention strategies may
      utilize information about students' impulsivity facets to address their binge
      drinking and alcohol-related consequences.

PMID- 24901737
TI  - Expression of a vacuole-localized BURP-domain protein from soybean (SALI3-2)
      enhances tolerance to cadmium and copper stresses.
AB  - The plant-specific BURP family proteins play diverse roles in plant development
      and stress responses, but the function mechanism of these proteins is still
      poorly understood. Proteins in this family are characterized by a highly
      conserved BURP domain with four conserved Cys-His repeats and two other Cys,
      indicating that these proteins potentially interacts with metal ions. In this
      paper, an immobilized metal affinity chromatography (IMAC) assay showed that the
      soybean BURP protein SALI3-2 could bind soft transition metal ions (Cd(2+),
      Co(2+), Ni(2+), Zn(2+) and Cu(2+)) but not hard metal ions (Ca(2+) and Mg(2+)) in
      vitro. A subcellular localization analysis by confocal laser scanning microscopy
      revealed that the SALI3-2-GFP fusion protein was localized to the vacuoles.
      Physiological indexes assay showed that Sali3-2-transgenic Arabidopsis thaliana
      seedlings were more tolerant to Cu(2+) or Cd(2+) stresses than the wild type. An
      inductively coupled plasma optical emission spectrometry (ICP-OES) analysis
      illustrated that, compared to the wild type seedlings the Sali3-2-transgenic
      seedlings accumulated more cadmium or copper in the roots but less in the upper
      ground tissues when the seedlings were exposed to excessive CuCl2 or CdCl2
      stress. Therefore, our findings suggest that the SALI3-2 protein may confer
      cadmium (Cd(2+)) and copper (Cu(2+)) tolerance to plants by helping plants to
      sequester Cd(2+) or Cu(2+) in the root and reduce the amount of heavy metals
      transported to the shoots.

PMID- 24901738
TI  - Quantification of larval zebrafish motor function in multiwell plates using open
      source MATLAB applications.
AB  - This article describes a method to quantify the movements of larval zebrafish in
      multiwell plates, using the open-source MATLAB applications LSRtrack and
      LSRanalyze. The protocol comprises four stages: generation of high-quality,
      flatly illuminated video recordings with exposure settings that facilitate object
      recognition; analysis of the resulting recordings using tools provided in
      LSRtrack to optimize tracking accuracy and motion detection; analysis of tracking
      data using LSRanalyze or custom MATLAB scripts; and implementation of validation
      controls. The method is reliable, automated and flexible, requires <1 h of hands
      on work for completion once optimized and shows excellent signal:noise
      characteristics. The resulting data can be analyzed to determine the following:
      positional preference; displacement, velocity and acceleration; and duration and
      frequency of movement events and rest periods. This approach is widely applicable
      to the analysis of spontaneous or stimulus-evoked zebrafish larval
      neurobehavioral phenotypes resulting from a broad array of genetic and
      environmental manipulations, in a multiwell plate format suitable for high
      throughput applications. 

PMID- 24901739
TI  - Tobacco rattle virus-based virus-induced gene silencing in Nicotiana benthamiana.
AB  - Tobacco rattle virus (TRV)-based virus-induced gene silencing (VIGS) is widely
      used in various plant species to downregulate the expression of a target plant
      gene. TRV is a bipartite, positive-strand RNA virus with the TRV1 and TRV2
      genomes. To induce post-transcriptional gene silencing (PTGS), the TRV2 genome is
      genetically modified to carry a fragment of the target gene and delivered into
      the plant (along with the TRV1 genome) by agroinoculation. TRV1- and TRV2
      carrying Agrobacterium strains are then co-inoculated into 3-week-old plant
      leaves by one of three methods: a needleless syringe, the agrodrench method or by
      pricking with a toothpick. Target gene silencing occurs in the newly developed
      noninoculated leaves within 2-3 weeks of TRV inoculation. The TRV-VIGS protocol
      described here takes only 4 weeks to implement, and it is faster and easier to
      perform than other gene silencing techniques that are currently available.
      Although we use Nicotiana benthamiana as an example, the protocol is adaptable to
      other plant species. 

PMID- 24901740
TI  - In vivo antigen-driven plasmablast enrichment in combination with antigen
      specific cell sorting to facilitate the isolation of rare monoclonal antibodies
      from human B cells.
AB  - The ability to rapidly generate large panels of antigen-specific human antibodies
      in a rodent would enable the efficient discovery of novel therapeutically useful
      antibodies. We have developed a system wherein human antigen-specific antibody
      secreting plasmablasts can be enriched in vivo, in a severe combined
      immunodeficient (SCID)/beige mouse host. The antigen-specific plasmablasts can
      then be sorted by flow cytometry, enabling single-cell cloning and expression of
      fully human immunoglobulin-G. By using this technique, we have generated four
      broadly reactive anti-influenza A antibodies. Therefore, the method described
      here is useful for the identification of rare functional antibodies. This
      protocol takes ~1 month to complete, from the time of human vaccination to the
      cloning of heavy- and light-chain genes. For additional small-scale transient
      expression, purification and binding analysis, the protocol would take an
      additional month. 

PMID- 24901743
TI  - Distance-determined sensitivity in attenuated total reflection-surface enhanced
      infrared absorption spectroscopy: aptamer-antigen compared to antibody-antigen.
AB  - Distance-dependent signal intensity in immunoassay by attenuated total reflection
      surface enhanced infrared absorption spectroscopy is demonstrated by controlling
      the distance of target proteins away from the enhancement substrate. Based on
      this optical near-field effect, sensitive detection of protein molecules with a
      detection limit of 0.6 nM and investigation of the kinetics and thermodynamics of
      protein-aptamer/antibody interactions can be achieved. 

PMID- 24901741
TI  - Liposome display for in vitro selection and evolution of membrane proteins.
AB  - Liposome display is a novel method for in vitro selection and directed evolution
      of membrane proteins. In this approach, membrane proteins of interest are
      displayed on liposome membranes through translation from a single DNA molecule by
      using an encapsulated cell-free translation system. The liposomes are probed with
      a fluorescence indicator that senses membrane protein activity and selected using
      a fluorescence-activated cell sorting (FACS) instrument. Consequently, DNA
      encoding a protein with a desired function can be obtained. By implementing this
      protocol, researchers can process a DNA library of 10(7) different mutants. A
      single round of the selection procedure requires 24 h for completion, and
      multiple iterations of this technique, which take 1-5 weeks, enable the isolation
      of a desired gene. As this protocol is conducted entirely in vitro, it enables
      the engineering of various proteins, including pore-forming proteins,
      transporters and receptors. As a useful example of the approach, here we detail a
      procedure for the in vitro evolution of alpha-hemolysin from Staphylococcus
      aureus for its pore-forming activity. 

PMID- 24901742
TI  - Telehealth distance education course in Latin America: analysis of an experience
      involving 15 countries.
AB  - BACKGROUND: Telehealth activities are already going on in many Latin American
      countries. This article aims to present and evaluate a distance learning
      telehealth training course in the region. MATERIALS AND METHODS: This was a cross
      sectional descriptive study. A coordinating committee was formed, composed of
      medical school faculty from 15 countries, which defined the course's syllabus,
      teaching model, and mentoring structure. A questionnaire was prepared, using a
      Likert scale, in order to verify if the parameters of gender, age, professional
      category, postgraduate degree, and experience in distance education indicated any
      difference in relation to the course evaluation. The responses were analyzed by
      chi-squared test, considering as significant a value of p<0.05. RESULTS: Of the
      353 enrolled participants, 251 (71.10%) did the basic modules, and 96 (43.91%)
      completed the full training. In relation to the overall course assessment, it was
      considered excellent or good by 80.92% of participants, the mentors received
      positive evaluations by 72.83% of students, the course content was evaluated as
      excellent or good by 87.4% of students, and 94.40% of participants would
      recommend it. As for the parameters assessed, only experience in distance
      education was statistically significant for the evaluation of the tutors.
      CONCLUSIONS: The results presented indicate an important concern on the part of
      the Latin American countries participating on the course in relation to
      telehealth training activities. Regarding course assessment, high approval rates
      in relation to tutoring, educational model, course content, and goals were noted,
      corroborating literature data. The experience of conducting a Latin American
      shared telehealth training course was indeed positive, contributing to the
      development of telehealth actions.

PMID- 24901744
TI  - Exploring the popularity, experiences, and beliefs surrounding gluten-free diets
      in nonceliac athletes.
AB  - Adherence to a gluten-free diet (GFD) for nonceliac athletes (NCA) has become
      increasingly popular despite a paucity of supportive medical or ergogenic
      evidence. This study aimed to quantify the demographics of NCA and determine
      associated experiences, perceptions, and sources of information related to GFD.
      Athletes (n = 910, female = 528, no gender selected = 5) completed a 17-question
      online survey. Forty-one percent of NCA respondents, including 18-world and/or
      Olympic medalists, follow a GFD 50-100% of the time (GFD > 50): only 13% for
      treatment of reported medical conditions with 57% self-diagnosing their gluten
      sensitivity. The GFD > 50 group characteristics included predominantly endurance
      sport athletes (70.0%) at the recreationally competitive level (32.3%), between
      31 and 40 years of age (29.1%). Those who follow a GFD > 50 reported
      experiencing, abdominal/gastrointestinal (GI) symptoms alone (16.7%) or in
      conjunction with two (30.7%) or three (35.7%) additional symptoms (e.g., fatigue)
      believed to be triggered by gluten. Eighty-four percent of GFD > 50 indicated
      symptom improvement with gluten-removal. Symptom-based and non-symptom-based self
      diagnosed gluten-sensitivity (56.7%) was the primary reason for adopting a GFD.
      Leading sources of GFD information were online (28.7%), trainer/coach (26.2%) and
      other athletes (17.4%). Although 5-10% of the general population is estimated to
      benefit clinically from a GFD a higher prevalence of GFD adherence was found in
      NCA (41.2%). Prescription of a GFD among many athletes does not result from
      evidence-based practice suggesting that adoption of a GFD in the majority of
      cases was not based on medical rationale and may be driven by perception that
      gluten removal provides health benefits and an ergogenic edge in NCA. 

PMID- 24901745
TI  - Survival of organic materials in hypervelocity impacts of ice on sand, ice, and
      water in the laboratory.
AB  - The survival of organic molecules in shock impact events has been investigated in
      the laboratory. A frozen mixture of anthracene and stearic acid, solvated in
      dimethylsulfoxide (DMSO), was fired in a two-stage light gas gun at speeds of ~2
      and ~4 km s(-1) at targets that included water ice, water, and sand. This
      involved shock pressures in the range of 2-12 GPa. It was found that the
      projectile materials were present in elevated quantities in the targets after
      impact and in some cases in the crater ejecta as well. For DMSO impacting water
      at 1.9 km s(-1) and 45 degrees  incidence, we quantify the surviving fraction
      after impact as 0.44+/-0.05. This demonstrates successful transfer of organic
      compounds from projectile to target in high-speed impacts. The range of impact
      speeds used covers that involved in impacts of terrestrial meteorites on the
      Moon, as well as impacts in the outer Solar System on icy bodies such as Pluto.
      The results provide laboratory evidence that suggests that exogenous delivery of
      complex organic molecules from icy impactors is a viable source of such material
      on target bodies.

PMID- 24901746
TI  - A literature review on the relationship between infertility and sexual
      dysfunction: does fun end with baby making?
AB  - OBJECTIVE: To analyse the relationship between infertility and sexuality, and the
      effect of assisted reproductive technology (ART) on a couple's sexual
      relationship. METHOD: The literature review is a result of a search that was
      undertaken with the keywords 'infertility' and 'sexuality' in PubMed from 2000
      until 2013. RESULTS: Even though abstinence or inadequate sexual activity are
      often reported in infertile couples, sexual disorders rarely cause infertility.
      They usually arise, instead, as a result of involuntary childlessness and
      assisted reproduction. Qualitative studies provide a detailed description of the
      impact of infertility and its treatment on the couples' sexual relationship,
      along with its specific gender effects, yet it is difficult to set standardised
      parameters to quantify sexual strain and the reliability of the studies available
      is limited by major drawbacks. CONCLUSIONS: Appropriate measures should be
      designed to identify sexual disorders in infertile couples, and the medical team
      should be trained to deal systematically with the couple's sexuality and propose
      strategies to overcome sexual disturbances. This approach could preserve the
      quality of the couple's sexual relationship and maximise pregnancy chances in
      ART.

PMID- 24901747
TI  - Optimization of absorption bands of dye-sensitized and perovskite tandem solar
      cells based on loss-in-potential values.
AB  - A numerical study of optimal bandgaps of light absorbers in tandem solar cell
      configurations is presented with the main focus on dye-sensitized solar cells
      (DSSCs) and perovskite solar cells (PSCs). The limits in efficiency and the
      expected improvements of tandem structures are investigated as a function of
      total loss-in-potential (V(L)), incident photon to current efficiency (IPCE) and
      fill factor (FF) of individual components. It is shown that the optimal
      absorption onsets are significantly smaller than those derived for multi-junction
      devices. For example, for double-cell devices the onsets are at around 660 nm and
      930 nm for DSSCs with iodide based electrolytes and at around 720 nm and 1100 nm
      for both DSSCs with cobalt based electrolytes and PSCs. Such configurations can
      increase the total sunlight conversion efficiency by about 35% in comparison to
      single-cell devices of the same VL, IPCE and FF. The relevance of such studies
      for tandem n-p DSSCs and for a proposed new configuration for PSCs is discussed.
      In particular, it is shown that maximum total losses of 1.7 V for DSSCs and 1.4 V
      for tandem PSCs are necessary to give any efficiency improvement with respect to
      the single bandgap device. This means, for example, a tandem n-p DSSC with TiO2
      and NiO porous electrodes will hardly work better than the champion single DSSC.
      A source code of the program used for calculations is also provided.

PMID- 24901748
TI  - Biographical sketch: Giles Brindley, FRS.

PMID- 24901749
TI  - Retraction of: Quiescent very small embryonic-like stem cells resist oncotherapy
      and can restore spermatogenesis in germ cell depleted mammalian testis.

PMID- 24901750
TI  - Mechanisms of change in adolescent substance use treatment: how does treatment
      work?
AB  - BACKGROUND: Adolescent substance use treatment outcome research generally shows
      small to moderate effects in reducing substance use, with no specific "brand" of
      treatment emerging as clearly superior to any other, and treatment gains that
      fade over time. The relatively weak and temporary effects of treatment call for
      improving the potency and durability of intervention effects. In response to this
      call, this critical narrative review summarizes research on mechanisms of change
      for both adults and adolescents in substance use treatment, with a particular
      focus on reviewing what is known regarding "how" adolescent substance use
      treatment works. METHODS: A comprehensive review of the adolescent (aged 11-18)
      substance use treatment literature was conducted to identify empirical studies
      that examined mediators of intervention effects. Relevant databases (e.g.,
      PsychINFO, MEDLINE) were searched using key words (e.g., "mediator"), and
      relevant articles from reference sections of identified studies and review papers
      were considered. RESULTS: Studies of mechanisms of psychotherapy change are rare
      in the adult, and particularly adolescent, substance use treatment outcome
      literature. The 4 adolescent studies that examined substance use treatment
      mechanisms found that positive social support, motivation to abstain, and
      positive parenting behaviors mediated treatment effects. To date, research has
      not supported therapy-specific mechanisms of change, finding instead that
      "common" processes of change largely account for improvements in outcome across
      distinct "brands" of treatment. CONCLUSIONS: The lack of empirical support for
      treatment-specific mechanisms of change may be due to the need for greater
      precision in defining and measuring treatment-specific causal chains. Future
      directions include neuroscience approaches to examining changes in brain
      functioning that are associated with treatment response and recovery and
      examining mechanisms in adaptive treatment designs, which can accommodate
      individual differences in targets for intervention and response to treatment.

PMID- 24901751
TI  - Measuring brain activity cycling (BAC) in long term EEG monitoring of preterm
      babies.
AB  - Measuring fluctuation of vigilance states in early preterm infants undergoing
      long term intensive care holds promise for monitoring their neurological well
      being. There is currently, however, neither objective nor quantitative methods
      available for this purpose in a research or clinical environment. The aim of this
      proof-of-concept study was, therefore, to develop quantitative measures of the
      fluctuation in vigilance states or brain activity cycling (BAC) in early preterm
      infants. The proposed measures of BAC were summary statistics computed on a
      frequency domain representation of the proportional duration of spontaneous
      activity transients (SAT%) calculated from electroencephalograph (EEG)
      recordings. Eighteen combinations of three statistics and six frequency domain
      representations were compared to a visual interpretation of cycling in the SAT%
      signal. Three high performing measures (band energy/periodogram: R = 0.809,
      relative band energy/nonstationary frequency marginal: R = 0.711, g
      statistic/nonstationary frequency marginal: R = 0.638) were then compared to a
      grading of sleep wake cycling based on the visual interpretation of the amplitude
      integrated EEG trend. These measures of BAC are conceptually straightforward,
      correlate well with the visual scores of BAC and sleep wake cycling, are robust
      enough to cope with the technically compromised monitoring data available in
      intensive care units, and are recommended for further validation in prospective
      studies. 

PMID- 24901752
TI  - Epidemiological survey of the first case of vancomycin-resistant Staphylococcus
      aureus infection in Europe.
AB  - We report on the follow-up and epidemiological study triggered by the isolation
      of the first vancomycin-resistant Staphylococcus aureus (VRSA) detected in
      Europe. The patient and 53 close contacts were screened for S. aureus
      colonization and all isolates recovered were characterized by multiple molecular
      typing methods. The VRSA remained confined to the infected foot of the patient
      and was not detected in any of the close contacts. Nasal colonization with S.
      aureus was detected in 20 subjects, of whom 15 carried methicilin-susceptible
      isolates with the remaining five harbouring methicilin-resistant S. aureus
      (MRSA). The majority of the isolates belonged to clones that have been previously
      shown to be prevalent in Portugal, both in the hospital setting and in the
      community. Only one isolate, an MRSA, was closely related to the VRSA. Like most
      of the characterized VRSA isolates from other countries, the VRSA isolated in
      Portugal belonged to clonal complex (CC) 5. Despite the absence of VRSA
      dissemination, the recent increase in the incidence of lineages belonging to CC5
      in some European countries, including Portugal, may result in more frequent
      opportunities for the emergence of VRSA.

PMID- 24901753
TI  - Effect of modulated-frequency and modulated-intensity transcutaneous electrical
      nerve stimulation after abdominal surgery: a randomized controlled trial.
AB  - PURPOSE: This study aimed to evaluate the effectiveness of transcutaneous
      electrical nerve stimulation (TENS) for treatment of postoperative pain and
      pulmonary functions (vital capacity [VC]; cough peak flow, [CPF]) in patients who
      underwent abdominal surgery. MATERIALS AND METHODS: Forty-eight patients were
      randomly allocated to receive TENS, placebo TENS, or no TENS (control) 1 hour a
      day for 3 days postoperatively. A 0-100 visual analog scale was used to assess
      pain at preintervention, mid-intervention, and postintervention on the third
      postoperative day. Pulmonary functions (VC, CPF) were evaluated by spirometer at
      preoperation (baseline) and at preintervention, mid-intervention, and
      postintervention on the third postoperative day. One-way analysis of variance was
      used to assess differences between groups at baseline. Mann-Whitney test was used
      to compare the control group with the placebo-TENS and TENS group, at each
      assessment timepoint. Two-way analysis of variance and Bonferroni post hoc test
      assessed the difference between the 2 (placebo-TENS*TENS) groups. A value of
      P<0.01 was considered statistically significant. RESULTS: The baselines were not
      significantly different between any groups. The TENS group had significant
      reductions in postoperative pain compared with the placebo group (P<0.01) and
      control group (P<0.01). There was also improvement in pulmonary functions (VC,
      CPF) at mid-TENS and post-TENS, but not in the placebo-TENS (P<0.01) or control
      groups (P<0.01). CONCLUSIONS: TENS is a valuable treatment to alleviate
      postoperative pain and improve pulmonary functions (ie, VC, CPF) in patients
      following abdominal surgery.

PMID- 24901754
TI  - Structure of the Pb2+-deprotonated dGMP complex in the gas phase: a combined MS
      MS/IRMPD spectroscopy/ion mobility study.
AB  - The structure of the Pb(2+)-deprotonated 2'-deoxyguanosine-5'-monophosphate
      (dGMP) complex, generated in the gas phase by electrospray ionization, was
      examined by combining tandem mass spectrometry, mid-infrared multiple-photon
      dissociation (IRMPD) spectroscopy and ion mobility. In the gas phase, the main
      binding site of Pb(2+) onto deprotonated dGMP is the deprotonated phosphate
      group, but the question is whether an additional stabilization of the metallic
      complex can occur via participation of the carbonyl group of guanine. Such
      macrochelates indeed correspond to the most stable structures according to
      theoretical calculations. A multiplexed experimental approach was used to
      characterize the gas-phase conformation of the metallic complex and hence
      determine the binding mode of Pb(2+) with [dGMP](-). MS/MS analysis, observation
      of characteristic bands by IRMPD spectroscopy, and measurement of the ion
      mobility collision cross section suggest that gaseous [Pb(dGMP)-H](+) complexes
      adopt a macrochelate folded structure, which consequently differs strongly from
      the zwitterionic forms postulated in solution from potentiometric studies. 

PMID- 24901755
TI  - Seasonal migration of Cnaphalocrocis medinalis (Lepidoptera: Crambidae) over the
      Bohai Sea in northern China.
AB  - The rice leaf roller, Cnaphalocrocis medinalis (Guenee), is a serious insect pest
      of rice with a strong migratory ability. Previous studies on the migration of C.
      medinalis were mostly carried out in tropical or subtropical regions, however,
      and what the pattern of seasonal movements this species exhibits in temperate
      regions (i.e. Northern China, where they cannot overwinter) remains unknown. Here
      we present data from an 11-year study of this species made by searchlight
      trapping on Beihuang Island (BH, 38 degrees 24'N; 120 degrees 55'E) in the centre
      of the Bohai Strait, which provides direct evidence that C. medinalis regularly
      migrates across this sea into northeastern agricultural region of China, and to
      take advantage of the abundant food resources there during the summer season.
      There was considerable seasonal variation in number of C. medinalis trapped on
      BH, and the migration period during 2003-2013 ranged from 72 to 122 days. Some
      females trapped in June and July showed a relatively higher proportion of mated
      and a degree of ovarian development suggesting that the migration of this species
      is not completely bound by the 'oogenesis-flight syndrome'. These findings
      revealed a new route for C. medinalis movements to and from Northeastern China,
      which will help us develop more effective management strategies against this
      pest.

PMID- 24901756
TI  - Early postnatal exposure to ultrafine particulate matter air pollution:
      persistent ventriculomegaly, neurochemical disruption, and glial activation
      preferentially in male mice.
AB  - BACKGROUND: Air pollution has been associated with adverse neurological and
      behavioral health effects in children and adults. Recent studies link air
      pollutant exposure to adverse neurodevelopmental outcomes, including increased
      risk for autism, cognitive decline, ischemic stroke, schizophrenia, and
      depression. OBJECTIVES: We sought to investigate the mechanism(s) by which
      exposure to ultrafine concentrated ambient particles (CAPs) adversely influences
      central nervous system (CNS) development. METHODS: We exposed C57BL6/J mice to
      ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient
      Particle System or to filtered air on postnatal days (PNDs) 4-7 and 10-13, and
      the animals were euthanized either 24 hr or 40 days after cessation of exposure.
      Another group of males was exposed at PND270, and lateral ventricle area, glial
      activation, CNS cytokines, and monoamine and amino acid neurotransmitters were
      quantified. RESULTS: We observed ventriculomegaly (i.e., lateral ventricle
      dilation) preferentially in male mice exposed to CAPs, and it persisted through
      young adulthood. In addition, CAPs-exposed males generally showed decreases in
      developmentally important CNS cytokines, whereas in CAPs-exposed females, we
      observed a neuroinflammatory response as indicated by increases in CNS cytokines.
      We also saw changes in CNS neurotransmitters and glial activation across multiple
      brain regions in a sex-dependent manner and increased hippocampal glutamate in
      CAPs-exposed males. CONCLUSIONS: We observed brain region- and sex-dependent
      alterations in cytokines and neurotransmitters in both male and female CAPs
      exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed
      only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has
      been associated with poor neurodevelopmental outcome, autism, and schizophrenia.
      Our findings suggest alteration of developmentally important neurochemicals and
      lateral ventricle dilation may be mechanistically related to observations linking
      ambient air pollutant exposure and adverse neurological/neurodevelopmental
      outcomes in humans.

PMID- 24901757
TI  - Gait training with a robotic leg brace after stroke: a randomized controlled
      pilot study.
AB  - OBJECTIVE: Robot-aided exercise therapy is a promising approach to enhance
      walking ability in stroke survivors. This study was designed to test a new
      robotic knee brace for restoring mobility in stroke survivors. DESIGN: Twenty
      four ambulatory individuals with chronic hemiparesis after stroke were enrolled
      in this pilot study. The participants were randomly assigned in equal numbers to
      either treatment with the experimental device or to a group exercise program and
      received a total of 18 hrs of their assigned therapy during a 6-wk training
      period. The primary outcome was gait velocity, as measured with the 10-m walk
      test. Secondary measures included 6-min walk test, Timed Up and Go test, Five
      Times-Sit-to-Stand test, Romberg test, Emory Functional Ambulation Profile, Berg
      Balance scale, and the California Functional Evaluation 40. RESULTS: Twenty
      subjects completed the entire protocol and all follow-up visits. No significant
      differences between the two groups were found for the primary outcome measure at
      either the completion of training (week 6) or at the 3-mo follow-up (week 19),
      with inconsistent findings for secondary measures. No within-group changes were
      seen in the primary outcome measure (10-m walk test) in either group. Within
      group improvements were seen in several of the secondary measures for both
      groups. No complications of robotic therapy were observed. CONCLUSIONS: Robotic
      therapy for ambulatory stroke patients with chronic hemiparesis using a robotic
      knee brace resulted in only modest functional benefits that were comparable with
      a group exercise intervention.

PMID- 24901758
TI  - Reactive postural control deficits in patients with posterior parietal cortex
      lesions after stroke and the influence of auditory cueing.
AB  - OBJECTIVE: The purpose of this study was to investigate the ways in which stroke
      induced posterior parietal cortex (PPC) lesions affect reactive postural
      responses and whether providing auditory cues modulates these responses. DESIGN:
      Seventeen hemiparetic patients after stroke, nine with PPC lesions (PPCLesion)
      and eight with intact PPCs (PPCSpared), and nine age-matched healthy adults
      completed a lateral-pull perturbation experiment under noncued and cued
      conditions. The activation rates of the gluteus medius muscle ipsilateral (GMi)
      and contralateral to the pull direction, the rates of occurrence of three types
      of GM activation patterns, and the GMi contraction latency were investigated.
      RESULTS: In noncued pulls toward the paretic side, of the three groups, the
      PPCLesion group exhibited the lowest activation rate (56%) of the GMi (P < 0.05),
      which is the primary postural muscle involved in this task, and the highest rate
      of occurrence (33%) of the gluteus medius muscle contralateral-activation-only
      pattern (P < 0.05), which is a compensatory activation pattern. In contrast, in
      cued pulls toward the paretic side, the PPCLesion group was able to increase the
      activation rate of the GMi to a level (81%) such that there became no significant
      differences in activation rate of the GMi among the three groups (P > 0.05).
      However, there were no significant differences in the GM activation patterns and
      GMi contraction latency between the noncued and cued conditions for the PPCLesion
      group (P > 0.05). CONCLUSIONS: The PPCLesion patients had greater deficits in
      recruiting paretic muscles and were more likely to use the compensatory muscle
      activation pattern for postural reactions than the PPCSpared patients, suggesting
      that PPC is part of the neural circuitry involved in reactive postural control in
      response to lateral perturbations. The auditory cueing used in this study,
      however, did not significantly modify the muscle activation patterns in the
      PPCLesion patients. More research is needed to explore the type and structure of
      cueing that could effectively improve patterns and speed of postural responses in
      these patients.

PMID- 24901759
TI  - Effects and effectiveness of dynamic arm supports: a technical review.
AB  - Numerous dynamic arm supports have been developed in recent decades to increase
      independence in the performance of activities of daily living. Much effort and
      money have been spent on their development and prescription, yet insight into
      their effects and effectiveness is lacking. This article is a systematic review
      of evaluations of dynamic arm supports. The 8 technical evaluations, 12 usability
      evaluations, and 27 outcome studies together make 47 evaluations. Technical
      evaluations were often used as input for new developments and directed at
      balancing quality, forces and torques, and range of motion of prototypes.
      Usability studies were mostly single-measure designs that had varying results as
      to whether devices were usable for potential users. An increased ability to
      perform activities of daily living and user satisfaction were reported in outcome
      studies. However, the use of dynamic arm supports in the home situation was
      reported to be low. Gaining insight into why devices are not used when their
      developers believe them to be effective seems crucial for every new dynamic arm
      support developed. The methodological quality of the outcome studies was often
      low, so it is important that this is improved in the future. 

PMID- 24901760
TI  - Inpatient rehabilitation outcomes for patients receiving left ventricular assist
      device.
AB  - OBJECTIVE: The aim of this study was to evaluate outcomes of patients
      participating in inpatient rehabilitation program after left ventricular assist
      device (LVAD) implantation. DESIGN: Medical records of 94 patients who received
      LVADs between January 1, 2008, and June 30, 2010, at the Mayo Clinic in
      Rochester, MN, were retrospectively reviewed for demographic data, and inpatient
      rehabilitation functional outcomes were measured by the Functional Independence
      Measure scale. RESULTS: After successful implantation of LVAD, the patients were
      either discharged directly home from acute care (44%) or admitted to inpatient
      rehabilitation (56%). The patients admitted to inpatient rehabilitation were
      older than those discharged home. They were also more medically complex and more
      likely to have the LVAD placed as destination therapy. At discharge, significant
      improvement occurred in 17 of the 18 activities evaluated by the Functional
      Independence Measure scale. The mean total Functional Independence Measure scale
      score at admission was 77.1 compared with a score of 95.2 at discharge (P <
      0.0001). CONCLUSIONS: Approximately half of the patients who received LVAD
      therapy were admitted in the inpatient rehabilitation. After the implantation of
      LVAD and inpatient rehabilitation, significant functional improvements were
      observed. Further studies addressing the role of inpatient rehabilitation for
      LVAD patients are warranted.

PMID- 24901761
TI  - Effect of postural balance training on gait parameters in children with cerebral
      palsy.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of dynamic bilateral
      postural stability on balance control and gait parameters in children with
      cerebral palsy. DESIGN: Thirty children with spastic diplegia (8-10 yrs) were
      included in this study. The children were randomly assigned into two groups:
      control group A and study group B. The children in both groups received
      traditional physical therapy program, 2 hrs per day for group A and 1.5 hrs
      followed by 30 mins of dynamic postural stability training program using the
      Biodex Stability System for group B. The treatment frequency was three sessions
      per week for 8 consecutive weeks on two stability levels (7 and 8). The
      participating children received pretreatment and posttreatment assessments using
      the Biodex Stability System to evaluate the stability indices (anteroposterior,
      mediolateral, and overall) at the two stability levels (7 and 8) and three
      dimensional motion analysis system (pro-reflex system) to evaluate the
      spatiotemporal parameters including step length, velocity, cycle time, stance,
      and swing phase percentage. RESULTS: The children in both groups showed
      significant improvements in the mean values of all measured variables after
      treatment indexed by a significant reduction in stability indices and improvement
      in gait parameters. The results also showed significant differences in all
      measured parameters in favor of group B, when compared with those in group A (P <
      0.01). CONCLUSIONS: Balance training on the Biodex Stability System could be a
      useful tool in conjunction with traditional physical therapy program for
      improving balance control and gait functions in children with spastic diplegic
      cerebral palsy.

PMID- 24901762
TI  - Rehabilomics research: a model for translational rehabilitation and comparative
      effectiveness rehabilitation research.

PMID- 24901763
TI  - Technique for fluorscopically guided injection for iliopsoas bursitis.

PMID- 24901764
TI  - Diffusion NMR study of generation-five PAMAM dendrimer materials.
AB  - Commercial generation-five poly(amidoamine) dendrimer material (G5c) was
      fractionated into its major structural components. Monomeric G5 (G5m; 21--30 kDa)
      was isolated to compare its functional properties to the G5c material. Diffusion
      ordered nuclear magnetic resonance spectroscopy was employed to measure the self
      diffusion coefficients and corresponding hydrodynamic radii of G5m and other G5c
      components as a function of dendrimer size (i.e., molecular weight) and tertiary
      structure (i.e., generational or oligomeric nature). It was found that the
      hydrodynamic radius (R(H)) scales with approximate numbers of atoms in the
      trailing generations, G5m, and oligomeric material at a rate of R(H)?N(0.35), in
      good agreement with previous reports of RH scaling for PAMAM dendrimer with
      generation. G5c materials can be thought of as a heterogeneous mixture of
      dendrimers ranging in size from trailing generation two to tetramers of G5,
      approximately the same in size as a G7 dendrimer, with G5m comprising ~65% of the
      material. The radius of hydration for G5m was measured to be 3.1 +/- 0.1 nm at pH
      7.4. The 10% swelling in response to a drop in pH observed for the G5c material
      was not observed for isolated G5m; however, the isolated G5--G5 dimers had an
      increase of 44% in R(H), indicating that the G5c pH response results from the
      increase in R(H) of the oligomeric fraction upon protonation. Finally, the data
      allow for an experimental test of the "slip" and "stick" boundary models of the
      Stokes--Einstein equation for PAMAM dendrimer in water.

PMID- 24901765
TI  - Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis.
AB  - An efficient enantioselective synthesis of the ABC tricyclic core of the
      anticancer drug Taxol is reported. The key step of this synthesis is a cascade
      metathesis reaction, which leads in one operation to the required tricycle if
      appropriate fine-tuning of the dienyne precursor is performed. 

PMID- 24901766
TI  - A novel cell traction force microscopy to study multi-cellular system.
AB  - Traction forces exerted by adherent cells on their microenvironment can mediate
      many critical cellular functions. Accurate quantification of these forces is
      essential for mechanistic understanding of mechanotransduction. However, most
      existing methods of quantifying cellular forces are limited to single cells in
      isolation, whereas most physiological processes are inherently multi-cellular in
      nature where cell-cell and cell-microenvironment interactions determine the
      emergent properties of cell clusters. In the present study, a robust finite
      element-method-based cell traction force microscopy technique is developed to
      estimate the traction forces produced by multiple isolated cells as well as cell
      clusters on soft substrates. The method accounts for the finite thickness of the
      substrate. Hence, cell cluster size can be larger than substrate thickness. The
      method allows computing the traction field from the substrate displacements
      within the cells' and clusters' boundaries. The displacement data outside these
      boundaries are not necessary. The utility of the method is demonstrated by
      computing the traction generated by multiple monkey kidney fibroblasts (MKF) and
      human colon cancerous (HCT-8) cells in close proximity, as well as by large
      clusters. It is found that cells act as individual contractile groups within
      clusters for generating traction. There may be multiple of such groups in the
      cluster, or the entire cluster may behave a single group. Individual cells do not
      form dipoles, but serve as a conduit of force (transmission lines) over long
      distances in the cluster. The cell-cell force can be either tensile or
      compressive depending on the cell-microenvironment interactions. 

PMID- 24901769
TI  - Neglected zoonotic diseases-the long and winding road to advocacy.
AB  - BACKGROUND: Years of advocacy for the neglected tropical diseases (NTDs) have
      focused the world's attention on these diseases of the poor, resulting most
      recently in the 2012 "London Declaration" and the recent World Health Assembly
      Resolution WHA66.12 on NTDs in May 2013. Control of the endemic neglected
      zoonotic diseases (NZDs) would benefit from a similar campaign, which needs the
      support of a global community. METHODOLOGY/PRINCIPAL FINDINGS: The resolutions
      from all 66 World Health Assembly (WHA) meetings held between 1948 and 2013 were
      examined to determine how many contain a specific focus on any of the following
      eight NZDs as defined by the World Health Organisation (WHO): anthrax, bovine
      tuberculosis (TB), brucellosis, Taenia solium cysticercosis, cystic
      echinococcosis (hydatidosis), leishmaniasis, rabies, and zoonotic human African
      trypanosomiasis (HAT or sleeping sickness). Twenty-one resolutions adopted in the
      16 assemblies between 1948 and 2013 targeted one or more of these eight NZDs,
      representing 4% of the total resolutions on infectious diseases passed to date.
      The 2013 adoption of Resolution WHA66.12 targeting all 17 NTDs marks a change in
      approach by the WHA. Whereas previous resolutions have targeted the NTDs as
      separate entities, the new approach of the combined resolution will help increase
      the overall momentum to target these ancient diseases as coendemic clusters in
      endemic countries. However, three major NZDs remain outside this recent
      resolution: anthrax, brucellosis, and bovine TB. CONCLUSIONS AND SIGNIFICANCE:
      The recent adoption of a specific resolution at the WHA in 2013 that emphasises a
      One Health approach for the successful control of 17 NTDs is a major development
      in advocacy. However, recognition of the importance of three major NZDs to public
      health in endemic countries-anthrax, brucellosis, and bovine tuberculosis-is
      still lacking despite being prioritised by the WHA as early as the 1950s. Global
      advocacy for control of the NZDs as a whole would similarly benefit from adoption
      of a One Health approach as is promoted for the NTDs under WHA66.12.

PMID- 24901767
TI  - Fibre-specific responses to endurance and low volume high intensity interval
      training: striking similarities in acute and chronic adaptation.
AB  - The current study involved the completion of two distinct experiments. Experiment
      1 compared fibre specific and whole muscle responses to acute bouts of either low
      volume high-intensity interval training (LV-HIT) or moderate-intensity continuous
      endurance exercise (END) in a randomized crossover design. Experiment 2 examined
      the impact of a six-week training intervention (END or LV-HIT; 4 days/week), on
      whole body and skeletal muscle fibre specific markers of aerobic and anaerobic
      capacity. Six recreationally active men (Age: 20.7 +/- 3.8 yrs; VO2peak: 51.9 +/-
      5.1 mL/kg/min) reported to the lab on two separate occasions for experiment 1.
      Following a muscle biopsy taken in a fasted state, participants completed an
      acute bout of each exercise protocol (LV-HIT: 8, 20-second intervals at ~ 170% of
      VO2peak separated by 10 seconds of rest; END: 30 minutes at ~ 65% of VO2peak),
      immediately followed by a muscle biopsy. Glycogen content of type I and IIA
      fibres was significantly (p<0.05) reduced, while p-ACC was significantly
      increased (p<0.05) following both protocols. Nineteen recreationally active males
      (n = 16) and females (n = 3) were VO2peak-matched and assigned to either the LV
      HIT (n = 10; 21 +/- 2 yrs) or END (n = 9; 20.7 +/- 3.8 yrs) group for experiment
      2. After 6 weeks, both training protocols induced comparable increases in aerobic
      capacity (END: Pre: 48.3 +/- 6.0, Mid: 51.8 +/- 6.0, Post: 55.0 +/- 6.3 mL/kg/min
      LV-HIT: Pre: 47.9 +/- 8.1, Mid: 50.4 +/- 7.4, Post: 54.7 +/- 7.6 mL/kg/min),
      fibre-type specific oxidative and glycolytic capacity, glycogen and IMTG stores,
      and whole-muscle capillary density. Interestingly, only LV-HIT induced greater
      improvements in anaerobic performance and estimated whole-muscle glycolytic
      capacity. These results suggest that 30 minutes of END exercise at ~ 65% VO2peak
      or 4 minutes of LV-HIT at ~ 170% VO2peak induce comparable changes in the intra
      myocellular environment (glycogen content and signaling activation);
      correspondingly, training-induced adaptations resulting for these protocols, and
      other HIT and END protocols are strikingly similar.

PMID- 24901768
TI  - Coriandrum sativum L. (Coriander) essential oil: antifungal activity and mode of
      action on Candida spp., and molecular targets affected in human whole-genome
      expression.
AB  - Oral candidiasis is an opportunistic fungal infection of the oral cavity with
      increasingly worldwide prevalence and incidence rates. Novel specifically
      targeted strategies to manage this ailment have been proposed using essential
      oils (EO) known to have antifungal properties. In this study, we aim to
      investigate the antifungal activity and mode of action of the EO from Coriandrum
      sativum L. (coriander) leaves on Candida spp. In addition, we detected the
      molecular targets affected in whole-genome expression in human cells. The EO
      phytochemical profile indicates monoterpenes and sesquiterpenes as major
      components, which are likely to negatively impact the viability of yeast cells.
      There seems to be a synergistic activity of the EO chemical compounds as their
      isolation into fractions led to a decreased antimicrobial effect. C. sativum EO
      may bind to membrane ergosterol, increasing ionic permeability and causing
      membrane damage leading to cell death, but it does not act on cell wall
      biosynthesis-related pathways. This mode of action is illustrated by
      photomicrographs showing disruption in biofilm integrity caused by the EO at
      varied concentrations. The EO also inhibited Candida biofilm adherence to a
      polystyrene substrate at low concentrations, and decreased the proteolytic
      activity of Candida albicans at minimum inhibitory concentration. Finally, the EO
      and its selected active fraction had low cytotoxicity on human cells, with
      putative mechanisms affecting gene expression in pathways involving chemokines
      and MAP-kinase (proliferation/apoptosis), as well as adhesion proteins. These
      findings highlight the potential antifungal activity of the EO from C. sativum
      leaves and suggest avenues for future translational toxicological research. 

PMID- 24901771
TI  - Editor's introduction.

PMID- 24901770
TI  - The C-TERMINUS of AtGRIP is crucial for its self-association and for targeting to
      Golgi stacks in Arabidopsis.
AB  - BACKGROUND: In animals and fungi, dimerization is crucial for targeting GRIP
      domain proteins to the Golgi apparatus. Only one gene in the Arabidopsis genome,
      AtGRIP, codes for a GRIP domain protein. It remains unclear whether AtGRIP has
      properties similar to those of GRIP domain proteins. RESULTS: In this study,
      western blot and yeast two-hybrid analyses indicated that AtGRIPs could form a
      parallel homodimer. In addition, yeast two-hybrid analysis indicated that
      AtGRIPaa711-753, AtGRIPaa711-766 and AtGRIPaa711-776 did not interact with
      themselves, but the intact GRIP domain with the AtGRIP C-terminus did. Confocal
      microscopy showed that only an intact GRIP domain with an AtGRIP C-terminus could
      localize to the Golgi stacks in Arabidopsis leaf protoplasts. A BLAST analysis
      showed that the C-terminus of GRIP proteins was conserved in the plant kingdom.
      Mutagenesis and yeast two-hybrid analyses showed that the L742 of AtGRIP
      contributed to dimerization and was crucial for Golgi localization. CONCLUSIONS:
      These results indicate that the C-terminus of GRIP proteins is essential for self
      association and for targeting of Golgi stacks in plant cells. We suggest that
      several properties of GRIP proteins differ between plant and animal cells.

PMID- 24901772
TI  - Diagnostic criteria for nonviable pregnancy early in the first trimester.

PMID- 24901773
TI  - Waiting, not rushing, to diagnose a failed pregnancy.

PMID- 24901774
TI  - National ultrasound curriculum for medical students.
AB  - Ultrasound (US) is an extremely useful diagnostic imaging modality because of its
      real-time capability, noninvasiveness, portability, and relatively low cost. It
      carries none of the potential risks of ionizing radiation exposure or intravenous
      contrast administration. For these reasons, numerous medical specialties now rely
      on US not only for diagnosis and guidance for procedures, but also as an
      extension of the physical examination. In addition, many medical school educators
      recognize the usefulness of this technique as an aid to teaching anatomy,
      physiology, pathology, and physical diagnosis. Radiologists are especially
      interested in teaching medical students the appropriate use of US in clinical
      practice. Educators who recognize the power of this tool have sought to
      incorporate it into the medical school curriculum. The basic question that
      educators should ask themselves is: "What should a student graduating from
      medical school know about US?" To aid them in answering this question, US
      specialists from the Society of Radiologists in Ultrasound and the Alliance of
      Medical School Educators in Radiology have collaborated in the design of a US
      curriculum for medical students. The implementation of such a curriculum will
      vary from institution to institution, depending on the resources of the medical
      school and space in the overall curriculum. Two different examples of how US can
      be incorporated vertically or horizontally into a curriculum are described, along
      with an explanation as to how this curriculum satisfies the Accreditation Council
      for Graduate Medical Education competencies, modified for the education of our
      future physicians.

PMID- 24901776
TI  - Invited commentary on American College of Radiology Appropriateness Criteria
      endometrial carcinoma.

PMID- 24901775
TI  - ACR Appropriateness Criteria(r) pretreatment evaluation and follow-up of
      endometrial cancer.
AB  - Endometrial cancer is the most common gynecologic and the fourth most common
      malignancy in women in the United States. Cross-sectional imaging plays a vital
      role in pretreatment assessment of endometrial cancers and should be viewed as a
      complementary tool for surgical evaluation and planning of these patients.
      Although transvaginal US remains the preferred examination for the screening
      purposes, MRI has emerged as the modality of choice for the staging of
      endometrial cancer and imaging assessment of recurrence or treatment response. A
      combination of dynamic contrast-enhanced and diffusion weighted MRI provides the
      highest accuracy for the staging. Both CT and MRI perform equivalently for
      assessing nodal involvement or distant metastasis. PET-CT is more appropriate for
      assessing lymphadenopathy in high-grade FDG-avid tumors or for clinically
      suspected recurrence after treatment. An appropriate use and guidelines of
      imaging techniques in diagnosis, staging, and detection of endometrial cancer and
      treatment of recurrent disease are reviewed.The American College of Radiology
      Appropriateness Criteria are evidence-based guidelines for specific clinical
      conditions that are reviewed every two years by a multidisciplinary expert panel.
      The guideline development and review include an extensive analysis of current
      medical literature from peer reviewed journals and the application of a well
      established consensus methodology (modified Delphi) to rate the appropriateness
      of imaging and treatment procedures by the panel. In those instances where
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging or treatment. 

PMID- 24901777
TI  - The investigation of correlation between semen analysis parameters and
      intraparenchymal testicular spectral Doppler indices in patients with clinical
      varicocele.
AB  - OBJECTIVES: Our aim was to evaluate the effect of clinical varicocele on
      testicular microcirculation measured by spectral Doppler analysis and investigate
      the correlation between Doppler ultrasonographic findings and semen parameters.
      METHODS: Fifty patients who received a diagnosis of clinical varicocele in the
      Urology Department of our university hospital were enrolled in this prospective
      study. Varicocele grades were determined according to sonographic parameters, and
      a scrotal vein with a diameter of 2.5 mm or greater on color Doppler
      ultrasonography was included in the study. Spectral Doppler measurements of
      testicular arteries (peak systolic [PSV]/end-diastolic velocity [EDV],
      resistivity index [RI], pulsatility index [PI]) were measured from capsular and
      intratesticular branches of testicular arteries. All the patients were also
      assessed by semen analysis. RESULTS: Mean age was 29.08 +/- 5.42 years (range, 18
      45 years). Among the whole study population, 22 men had isolated left varicocele,
      and 28 had bilateral varicoceles. No statistically significant correlation was
      found between the Doppler parameters: RI, PI, and EDV, and semen analysis
      parameters: count, motility, volume, and morphology. On the other hand, both in
      unilateral and bilateral varicocele cases, PSV was found to be significantly
      correlated with sperm count (P < 0.05). CONCLUSIONS: Spectral Doppler analysis
      can provide valuable information as a noninvasive method to assess the
      hemodynamic changes and testicular microcirculation status in cases of clinical
      varicocele. However, RI, PI, and EDV values of capsular and intraparenchymal
      branches of testicular arteries may not be used as indicators of semen parameter
      deterioration. Hopefully, PSV measurement may give more conclusive data to
      predict sperm count. In addition, the cutoff value for this index has to be
      determined for future studies.

PMID- 24901778
TI  - Ultrasound measurements of the bile ducts and gallbladder: normal ranges and
      effects of age, sex, cholecystectomy, and pathologic states.
AB  - OBJECTIVE: The objectives of this study were to determine the normal values and
      ranges for bile duct and gallbladder measurements, adjusted for demographic data,
      and to assess the effects of a variety of pathologic states on these values.
      METHODS: Four thousand one hundred nineteen abdominal ultrasounds were
      retrospectively analyzed. The values for the extrahepatic bile duct (EHD), left
      (LIHD) and right (RIHD) intrahepatic ducts, gallbladder wall thickness, and
      gallbladder volume in "normal" patients were evaluated with respect to age, sex,
      ethnicity, and cholecystectomy status. These values were compared using
      multivariate analysis to those in a variety of diseased states, including
      cirrhosis, fatty liver, gallstones, sludge, cholecystitis, and biliary
      obstruction. RESULTS: One thousand four hundred eighty-four of the 4119
      examinations were classified as normal. The mean EHD, RIHD, LIHD, and gallbladder
      wall thickness and volume measurements in normal patients were 3.8 +/- 1.6 mm,
      1.9 +/- 1.9 mm, 1.9 +/- 1.1 mm, 2.6 +/- 1.6 mm, and 242 +/- 234 mL,
      respectively.There were small increases in EHD diameter with age (+0.02 +/- 0.11
      mm/y, P < 0.001), female sex (+0.3 +/- 1.6 mm, P < 0.0001), and cholecystectomy
      (+1.0 +/- 1.6 mm, P < 0.0001) and a small decrease with fatty liver (-0.4 +/- 1.6
      mm, P = 0.0003). The gallbladder wall was thicker in patients with gallstones
      (+0.4 +/- 1.4 mm, P = 0.0049), sludge (+0.5 +/- 1.4 mm, P = 0.0019), and acute
      cholecystitis (+3.1 +/- 1.6 mm, P < 0.0001). With biliary obstruction, the mean
      EHD, RIHD, LIHD, and gallbladder volume measurements were 6.0 +/- 2.1 mm, 4.2 +/-
      1.4 mm, 4.1 +/- 1.4 mm, and 171 +/- 207 mL, respectively (P < 0.0001 for all
      values). CONCLUSIONS: This study clarifies normal values and ranges for bile duct
      and gallbladder measurements, adjusted for demographic data, and evaluates these
      measurements in a variety of common pathologic states.

PMID- 24901779
TI  - Sonographic appearance of adnexal torsion, correlation with other imaging
      modalities, and clinical history.
AB  - This pictorial essay illustrates the varied imaging appearances of adnexal
      torsion and its diagnostic pitfalls. This is a difficult diagnosis with many
      false positives and false negatives. Diagnosis is mostly based on clinical
      history and ultrasound examination, with computed tomography and/or magnetic
      resonance used to support the diagnosis and to exclude other pathologies.

PMID- 24901780
TI  - Teaching ultrasound in developing countries: issues to consider when working in
      small medical facilities.
AB  - The author provides some suggestions for those considering travel to developing
      countries to provide training in ultrasound at small medical facilities. Issues
      discussed will include planning before the trip, personal safety and health while
      there, as well as equipment and travel issues.

PMID- 24901781
TI  - Determination of fetal lung maturity using magnetic resonance imaging signal
      intensity measurements.
AB  - PURPOSE: The objective of this study was to determine if magnetic resonance
      signal intensity measurements can be used to predict gestational age and hence
      fetal lung maturity. METHODS: This institutional review board-approved study was
      a retrospective review of 394 fetal magnetic resonance imaging cases from a
      single institution for the years 2001 to 2011. For each case, T1- and T2-weighted
      sequences were selected for data collection. A single reviewer obtained 10
      regions of interest (when possible) from each scan (fetal lung, fetal liver,
      fetal muscle, fetal spleen, and maternal urine, for both T1- and T2-weighted
      sequences). The medical record was searched for relevant information including
      best estimate of gestational age, Apgar scores, karyotype, and fetal diagnosis. A
      variety of organ-to-organ ratios and direct organ signal intensity measurements
      were assessed for correlation with gestational age. RESULTS: Three hundred thirty
      five cases met inclusion criteria with gestational ages ranging from 17 to 39
      weeks (mean, 28.6 weeks). A significant relationship between magnetic resonance
      signal intensity ratios and gestational age was demonstrated on the T2 lung-to
      liver, T2 lung-to-spleen, T2 lung-to-muscle, T1 lung-to-liver, and T1 lung-to
      spleen ratios (P < 0.05). T2 lung-to-liver and T2 lung-to-muscle demonstrated the
      strongest relationship with gestational age (best correlation r = 0.483, P <
      0.001). T1 lung-to-liver and T1 lung-to-spleen demonstrated inverse relationships
      with gestational age (r = -0.174 [P = 0.03] and r = -0.236 [P = 0.02],
      respectively). CONCLUSIONS: A significant correlation between multiple signal
      intensity ratios and gestational age is demonstrated. However, the large
      variances preclude a clinically useful relationship.

PMID- 24901782
TI  - Manufacturing models of fetal malformations built from 3-dimensional ultrasound,
      magnetic resonance imaging, and computed tomography scan data.
AB  - Technological innovations accompanying advances in medicine have given rise to
      the possibility of obtaining better-defined fetal images that assist in medical
      diagnosis and contribute toward genetic counseling offered to parents during the
      prenatal period. In this article, we show our innovative experience of diagnosing
      fetal malformations through correlating 3-dimensional ultrasonography, magnetic
      resonance imaging, and computed tomography, which are accurate techniques for
      fetal assessment, with a fetal image reconstruction technique to create physical
      fetal models.

PMID- 24901783
TI  - International visiting professorships: my experience in South Africa.

PMID- 24901787
TI  - Altered expression of circulating microRNA in plasma of patients with primary
      osteoarthritis and in silico analysis of their pathways.
AB  - OBJECTIVE: To analyze a set of circulating microRNA (miRNA) in plasma from
      patients with primary Osteoarthritis (OA) and describe the biological
      significance of altered miRNA in OA based on an in silico analysis of their
      target genes. METHODS: miRNA expression was analyzed using TaqMan Low Density
      Arrays and independent assays. The search for potential messenger RNA (mRNA)
      targets of the differentially expressed miRNA was performed by means of the
      miRWalk and miRecords database; we conducted the biological relevance of the
      predicted miRNA targets by pathway analysis with the Reactome and DAVID
      databases. RESULTS: We measured the expression of 380 miRNA in OA; 12 miRNA were
      overexpressed under the OA condition (p value, <=0.05; fold change, >2). These
      results were validated by the detection of some selected miRNA by quantitative
      PCR (qPCR). In silico analysis showed that target messenger RNA (mRNA) were
      potentially regulated by these miRNA, including genes such as SMAD1, IL-1B,
      COL3A, VEGFA, and FGFR1, important in chondrocyte maintenance and
      differentiation. Some metabolic pathways affected by the miRNA: mRNA ratio are
      signaling Bone morphogenetic proteins (BMP), Platelet-derived growth factor
      (PDGF), and Nerve growth factor (NGF), these latter two involved in the process
      of pain. CONCLUSIONS: We identified 12 miRNA in the plasma of patients with
      primary OA. Specific miRNA that are altered in the disease could be released into
      plasma, either due to cartilage damage or to an inherent cellular mechanism.
      Several miRNA could regulate genes and pathways related with development of the
      disease; eight of these circulating miRNA are described, to our knowledge, for
      first time in OA.

PMID- 24901789
TI  - Exploring the polyadenylated RNA virome of sweet potato through high-throughput
      sequencing.
AB  - BACKGROUND: Viral diseases are the second most significant biotic stress for
      sweet potato, with yield losses reaching 20% to 40%. Over 30 viruses have been
      reported to infect sweet potato around the world, and 11 of these have been
      detected in China. Most of these viruses were detected by traditional detection
      approaches that show disadvantages in detection throughput. Next-generation
      sequencing technology provides a novel, high sensitive method for virus detection
      and diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We report the polyadenylated RNA
      virome of three sweet potato cultivars using a high throughput RNA sequencing
      approach. Transcripts of 15 different viruses were detected, 11 of which were
      detected in cultivar Xushu18, whilst 11 and 4 viruses were detected in Guangshu
      87 and Jingshu 6, respectively. Four were detected in sweet potato for the first
      time, and 4 were found for the first time in China. The most prevalent virus was
      SPFMV, which constituted 88% of the total viral sequence reads. Virus transcripts
      with extremely low expression levels were also detected, such as transcripts of
      SPLCV, CMV and CymMV. Digital gene expression (DGE) and reverse transcription
      polymerase chain reaction (RT-PCR) analyses showed that the highest viral
      transcript expression levels were found in fibrous and tuberous roots, which
      suggest that these tissues should be optimum samples for virus detection.
      CONCLUSIONS/SIGNIFICANCE: A total of 15 viruses were presumed to present in three
      sweet potato cultivars growing in China. This is the first insight into the sweet
      potato polyadenylated RNA virome. These results can serve as a basis for further
      work to investigate whether some of the 'new' viruses infecting sweet potato are
      pathogenic.

PMID- 24901788
TI  - Evidence for a catalytically and kinetically competent enzyme-substrate cross
      linked intermediate in catalysis by lipoyl synthase.
AB  - Lipoyl synthase (LS) catalyzes the final step in lipoyl cofactor biosynthesis:
      the insertion of two sulfur atoms at C6 and C8 of an (N(6)-octanoyl)-lysyl
      residue on a lipoyl carrier protein (LCP). LS is a member of the radical SAM
      superfamily, enzymes that use a [4Fe-4S] cluster to effect the reductive cleavage
      of S-adenosyl-l-methionine (SAM) to l-methionine and a 5'-deoxyadenosyl 5'
      radical (5'-dA(*)). In the LS reaction, two equivalents of 5'-dA(*) are generated
      sequentially to abstract hydrogen atoms from C6 and C8 of the appended octanoyl
      group, initiating sulfur insertion at these positions. The second [4Fe-4S]
      cluster on LS, termed the auxiliary cluster, is proposed to be the source of the
      inserted sulfur atoms. Herein, we provide evidence for the formation of a
      covalent cross-link between LS and an LCP or synthetic peptide substrate in
      reactions in which insertion of the second sulfur atom is slowed significantly by
      deuterium substitution at C8 or by inclusion of limiting concentrations of SAM.
      The observation that the proteins elute simultaneously by anion-exchange
      chromatography but are separated by aerobic SDS-PAGE is consistent with their
      linkage through the auxiliary cluster that is sacrificed during turnover.
      Generation of the cross-linked species with a small, unlabeled (N(6)-octanoyl)
      lysyl-containing peptide substrate allowed demonstration of both its chemical and
      kinetic competence, providing strong evidence that it is an intermediate in the
      LS reaction. Mossbauer spectroscopy of the cross-linked intermediate reveals that
      one of the [4Fe-4S] clusters, presumably the auxiliary cluster, is partially
      disassembled to a 3Fe-cluster with spectroscopic properties similar to those of
      reduced [3Fe-4S](0) clusters. 

PMID- 24901791
TI  - Pd-catalyzed regio- and stereoselective addition of boronic acids to
      silylacetylenes: a stereodivergent assembly of beta,beta-disubstituted
      alkenylsilanes and alkenyl halides.
AB  - An efficient Pd-catalyzed addition of boronic acids to silylacetylenes is
      described, providing beta,beta-disubstituted (E)- or (Z)-alkenylsilanes in
      satisfactory yields with excellent regio- and stereoselectivity under mild
      reaction conditions. It represents the first highly regio- and stereoselective
      addition of boronic acids to aryl and alkenyl silylacetylenes. Moreover, the
      sequential Pd-catalyzed boron addition/N-halosuccinimide-mediated
      halodesilylation reaction results in a stereodivergent approach to beta,beta
      disubstituted alkenyl halides, which can serve as versatile synthetic
      intermediates for the stereodivergent assembly of (E)- and (Z)-trisubstituted
      alkenes via transition-metal-catalyzed cross-coupling reactions. 

PMID- 24901790
TI  - Baseline CD4 cell counts of newly diagnosed HIV cases in China: 2006-2012.
AB  - BACKGROUND: Late diagnosis of HIV infection is common. We aim to assess the
      proportion of newly diagnosed HIV cases receiving timely baseline CD4 count
      testing and the associated factors in China. METHODS: Data were extracted from
      the Chinese HIV/AIDS Comprehensive Response Information Management System. Adult
      patients over 15 years old who had been newly diagnosed with HIV infection in
      China between 2006 and 2012 were identified. The study cohort comprised
      individuals who had a measured baseline CD4 count. RESULTS: Among 388,496 newly
      identified HIV cases, the median baseline CD4 count was 294 cells/ul (IQR: 130
      454), and over half (N = 130,442, 58.8%) were less than 350 cells/ul. The median
      baseline CD4 count increased from 221 (IQR: 63-410) in 2006 to 314 (IQR: 159-460)
      in 2012. A slight majority of patients (N = 221,980, 57.1%) received baseline CD4
      count testing within 6 months of diagnosis. The proportion of individuals who
      received timely baseline CD4 count testing increased significantly from 20.0% in
      2006 to 76.9% in 2012. Factors associated with failing to receiving timely CD4
      count testing were: being male (OR: 1.17, 95% CI: 1.15-1.19), age 55 years or
      older (OR:1.03, 95% CI: 1.00-1.06), educational attainment of primary school
      education or below (OR: 1.30, 95% CI: 1.28-1.32), infection with HIV through
      injection drug use (OR: 2.07, 95% CI: 2.02-2.12) or sexual contact and injection
      drug use (OR: 1.87, 95% CI: 1.76-1.99), diagnosis in a hospital (OR: 1.91, 95%
      CI: 1.88-1.95) or in a detention center (OR: 1.75, 95% CI: 1.70-1.80), and
      employment as a migrant worker (OR:1.55, 95% CI:1.53-1.58). CONCLUSION: The
      proportion of newly identified HIV patients receiving timely baseline CD4 testing
      has increased significantly in China from 2006-2012. Continued effort is needed
      for further promotion of early HIV diagnosis and timely baseline CD4 cell count
      testing.

PMID- 24901792
TI  - Prenatal maternal and possible transgenerational epigenetic effects on milk
      production.
AB  - This study investigated whether the prenatal maternal environment in dairy cattle
      influences the postnatal milking performance of the resulting daughters and grand
      daughters. Linear mixed models were used to analyse whole season milk production
      from ~ 46,000 Jersey and ~ 123,000 Holstein Friesian cows in their 1st and 2nd
      lactations. Variation in the prenatal environment was associated with a small but
      significant (P<0.05) proportion of the total phenotypic variation (0.010 to
      0.015) in all traits in Holstein Friesian cows and in the first lactation milk
      volume (0.011) and milk protein (0.011), and the second lactation milk fat
      (0.015) in the Jersey breed. This indicates that the prenatal environment does
      influence the adult performance of the subsequent daughter. Associations between
      daughter performance and dam and grand-dam traits indicative of their prenatal
      environment were also estimated. A one litre increase in the dam's herd test milk
      volume was associated with a 7.5 litre increase in the daughters' whole season
      milk yield and a 1% increase in either the dams' herd test milk fat or protein
      percentage was associated with a reduction in daughter whole season milk volume (
      49.6 and -45.0 litres for dam fat and protein, respectively). Similar results
      between the grand-dam herd test traits and the daughters' whole season milk
      production were observed with a 1% increase in either grand-dam milk fat or
      protein percentage associated with a reduction in daughter whole season milk
      yield (-34.7 and -9.7 litres for fat and protein, respectively). This study
      revealed that the prenatal environment of the dam and the grand-dam can influence
      milk production in the subsequent daughters, though the effects are small. The
      similarity of the results between the dam daughter and the grand-dam daughter
      analyses suggests that the majority of the prenatal maternal effects are mediated
      by epigenetic mechanisms.

PMID- 24901793
TI  - Longitudinal predictors of self-rated health and mortality in older adults.
AB  - INTRODUCTION: Few studies have compared the effects of demographic, cognitive,
      and behavioral factors of health and mortality longitudinally. We examined
      predictors of self-rated health and mortality at 3 points, each 2 years apart,
      over 4 years. METHODS: We used data from the 2006 wave of the Health and
      Retirement Study and health and mortality indicators from 2006, 2008, and 2010.
      We analyzed data from 17,930 adults (aged 50-104 y) to examine predictors of self
      rated health and data from a subgroup of 1,171 adults who died from 2006 through
      2010 to examine predictors of mortality. RESULTS: Time 1 depression was the
      strongest predictor of self-rated health at all points, independent of age and
      education. Education, mild activities, body mass index, delayed word recall, and
      smoking were all associated with self-rated health at each point and predicted
      mortality. Delayed word recall mediated the relationships of mild activity with
      health and mortality. Bidirectional mediation was found for the effects of mild
      activity and depression on health. CONCLUSION: Medical professionals should
      consider screening for depression and memory difficulties in addition to
      conducting medical assessments. These assessments could lead to more effective
      biopsychosocial interventions to help older adults manage risks for mortality.

PMID- 24901794
TI  - Using written narratives in public health practice: a creative writing
      perspective.
AB  - Narratives have become an increasingly common health communication tool in recent
      years. Vivid, engaging writing can help audiences identify with storytellers and
      understand health messages, but few public health practitioners are trained to
      create such stories. A transdisciplinary perspective, informed by both creative
      writing advice and evidence-based public health practices, can help public health
      professionals use stories more effectively in their work. This article provides
      techniques for creating written narratives that communicate health information
      for chronic disease prevention. We guide public health professionals through the
      process of soliciting, writing, and revising such stories, and we discuss
      challenges and potential solutions. 

PMID- 24901795
TI  - Defining powerhouse fruits and vegetables: a nutrient density approach.
AB  - National nutrition guidelines emphasize consumption of powerhouse fruits and
      vegetables (PFV), foods most strongly associated with reduced chronic disease
      risk; yet efforts to define PFV are lacking. This study developed and validated a
      classification scheme defining PFV as foods providing, on average, 10% or more
      daily value per 100 kcal of 17 qualifying nutrients. Of 47 foods studied, 41
      satisfied the powerhouse criterion and were more nutrient-dense than were non
      PFV, providing preliminary evidence of the validity of the classification scheme.
      The proposed classification scheme is offered as a tool for nutrition education
      and dietary guidance. 

PMID- 24901796
TI  - Public opinion on nutrition-related policies to combat child obesity, Los Angeles
      County, 2011.
AB  - We assessed public opinion on nutrition-related policies to address child
      obesity: a soda tax, restrictions on advertising unhealthy foods and beverages to
      children, and restrictions on siting fast food restaurants and convenience stores
      near schools. We analyzed data from 998 adults (aged >=18 years) in the 2011 Los
      Angeles County Health Survey. Support was highest for advertising restrictions
      (74%), intermediate for a soda tax (60%), and lowest for siting restrictions on
      fast food restaurants and convenience stores (44% and 37%, respectively). Support
      for food and beverage advertising restrictions and soda taxation is promising for
      future policy efforts to address child obesity. 

PMID- 24901797
TI  - Multiple mineralocorticoid response elements localized in different introns
      regulate intermediate conductance K+ (Kcnn4) channel expression in the rat distal
      colon.
AB  - An elevated plasma aldosterone and an increased expression of the intermediate
      conductance K(+) (IK/Kcnn4) channels are linked in colon. This observation
      suggests that the expression of Kcnn4 gene is controlled through the action of
      aldosterone on its cognate receptor (i.e., mineralocorticoid receptor; MR). In
      order to establish this, we performed chromatin immunoprecipitation (ChIP) assay
      to identify the MR response elements (MREs) in a region that spanned 20 kb
      upstream and 10 kb downstream of the presumed transcription start site (TSS)
      using chromatin from the colonic epithelial cells of normal and aldosterone
      treated rats. MREs were immunoprecipitated in an approximately 5 kb region that
      spanned the first and second introns in the aldosterone rats. These regions were
      individually cloned in luciferase-expression vector lacking enhancer activity.
      These clones were tested for enhancer activity in vitro by transfecting in
      HEK293T and CaCo2 cells with MR and aldosterone treatment. At least four regions
      were found to be responsive to the MR and aldosterone. Two regions were
      identified to contain MREs using bioinformatics tools. These clones lost their
      enhancer activity after mutation of the presumptive MREs, and thus, established
      the functionality of the MREs. The third and fourth clones did not contain any
      bioinformatically obvious MREs. Further, they lost their activity upon additional
      sub-cloning, which suggest cooperativity between the regions that were separated
      upon sub-cloning. These results demonstrate the presence of intronic MREs in
      Kcnn4 and suggest a highly cooperative interaction between multiple intronic
      response elements.

PMID- 24901799
TI  - Excited state chemistry of flavone derivatives in a confined medium: ESIPT
      emission in aqueous media.
AB  - The excited state behavior of two flavone derivatives 3-hydroxyflavone and 4'-N,N
      diethylaminoflavonol in a confined medium indicates that supramolecular effects
      could alter the nature of the fluorescence emission. Within the octa acid host
      the neutral unionized species of these two dyes are present showing large Stokes
      shifted emission due to intramolecular proton transfer, a pattern different from
      that in aqueous medium. 

PMID- 24901800
TI  - Endiandric acid analogues from Beilschmiedia ferruginea as dual inhibitors of Bcl
      xL/Bak and Mcl-1/Bid interactions.
AB  - A rapid screening by (1)H and (1)H-(13)C HSQC NMR spectroscopy of EtOAc extracts
      of Endiandra and Beilschmiedia species allowed the selection of Beilschmiedia
      ferruginea leaves and flowers extract for a chemical investigation, leading to
      the isolation of 11 new tetracyclic endiandric acid analogues, named ferrugineic
      acids A-K (1-11). Their structures were determined by 1D and 2D NMR spectroscopic
      analysis in combination with HRMS data. These compounds were assayed for Bcl-xL
      and Mcl-1 binding affinities. Ferrugineic acids B, C, and J (2, 3, and 10)
      exhibited significant binding affinity for both antiapoptotic proteins Bcl-xL (Ki
      = 19.2, 12.6, and 19.4 MUM, respectively) and Mcl-1 (Ki = 14.0, 13.0, and 5.2
      MUM, respectively), and ferrugineic acid D (4) showed only significant inhibiting
      activity for Mcl-1 (Ki = 5.9 MUM). 

PMID- 24901801
TI  - High-volume hemofiltration in children with acute liver failure*.
AB  - OBJECTIVES: High-volume hemofiltration has shown beneficial effects in severe
      sepsis and multiple organ failure, improving hemodynamics and fluid balance.
      Recent studies suggest that acute liver failure shares many pathophysiologic
      similarities with sepsis. Therefore, we assessed the systemic effects of high
      volume hemofiltration in children with acute liver failure. DESIGN: Retrospective
      observational cohort study. PATIENTS: Twenty-two children. SETTING: Forty-two-bed
      multidisciplinary pediatric and neonatal ICUs in a tertiary university hospital.
      INTERVENTION: We evaluated high-volume hemofiltration therapy as part of standard
      management of 22 children admitted in our unit for acute liver failure. Fifteen
      patients had fulminant hepatic failure, three had acute-on-chronic liver disease,
      and four had primary nonfunction. High-volume hemofiltration was initiated in
      patients requiring emergency liver transplantation and when hepatic
      encephalopathy grade higher than 2 and/or hemodynamic instability requiring
      vasopressors occurred. High-volume hemofiltration was defined by a flow of
      ultrafiltrate of more than 80 mL/kg/hr. Clinical and biological variables were
      assessed before and 24 and 48 hours after initiation of high-volume
      hemofiltration therapy. MEASUREMENTS AND MAIN RESULTS: High-volume hemofiltration
      was initiated with a median grade III of hepatic encephalopathy. The median flow
      of ultrafiltrate was 119 mL/kg/hr (range, 80-384). After 24 hours of high-volume
      hemofiltration treatment, we observed an increase in mean arterial pressure (p =
      0.0002) and a decrease in serum creatinine (p = 0.0002). In half of the patients,
      the encephalopathy grade decreased. After 48 hours of treatment, mean arterial
      pressure (p = 0.0005), grade of hepatic encephalopathy (p = 0.04), and serum
      creatinine (p = 0.0002) improved. Overall mortality was 45.4% (n = 10). Emergency
      liver transplantation was performed in eight children. Five patients
      spontaneously recovered liver function. CONCLUSIONS: High-volume hemofiltration
      therapy significantly improves hemodynamic stability and neurological status in
      children with acute liver failure awaiting for emergency liver transplantation.

PMID- 24901798
TI  - OsHUS1 facilitates accurate meiotic recombination in rice.
AB  - Meiotic recombination normally takes place between allelic sequences on homologs.
      This process can also occur between non-allelic homologous sequences. Such
      ectopic interaction events can lead to chromosome rearrangements and are normally
      avoided. However, much remains unknown about how these ectopic interaction events
      are sensed and eliminated. In this study, using a screen in rice, we
      characterized a homolog of HUS1 and explored its function in meiotic
      recombination. In Oshus1 mutants, in conjunction with nearly normal homologous
      pairing and synapsis, vigorous, aberrant ectopic interactions occurred between
      nonhomologous chromosomes, leading to multivalent formation and subsequent
      chromosome fragmentation. These ectopic interactions relied on programmed meiotic
      double strand breaks and were formed in a manner independent of the OsMER3
      mediated interference-sensitive crossover pathway. Although early homologous
      recombination events occurred normally, the number of interference-sensitive
      crossovers was reduced in the absence of OsHUS1. Together, our results indicate
      that OsHUS1 might be involved in regulating ectopic interactions during meiosis,
      probably by forming the canonical RAD9-RAD1-HUS1 (9-1-1) complex.

PMID- 24901802
TI  - Intensive care treatment of uncontrolled status epilepticus in children:
      systematic literature search of midazolam and anesthetic therapies*.
AB  - OBJECTIVE: A systematic literature search and review of the best evidence for
      intensive care treatment of refractory status epilepticus in children using
      continuous infusion of midazolam or anesthetic agents. DESIGN: MEDLINE and EMBASE
      search before December 2013 using key words and/or Medical Subject Headings
      identified English-language citations that were screened for eligibility and used
      if 1) the study was about high-dose benzodiazepine or anesthetic agent for
      children; 2) the treatment protocol was described and used for refractory status
      epilepticus; 3) the outcomes included seizure control; and 4) the series included
      at least five children. MAIN RESULTS: Sixteen studies (645 patients) were
      identified, including midazolam (nine studies), barbiturate (four studies), and
      other anesthetic approaches (three studies). When midazolam was used as the
      initial agent for refractory status epilepticus, the rate of clinical seizure
      control was 76%, which was achieved on average 41 minutes after starting the
      infusion. When midazolam was used in conjunction with continuous
      electroencephalography, the time to seizure control was much longer and the mean
      dose required for seizure control was 10.7 MUg/kg/min compared with a lower dose
      (2.8 MUg/kg/min) in the studies not using this form of monitoring, suggesting
      that continuous electroencephalography provided additional targets for treatment.
      Barbiturates were usually used after midazolam failed and treatment was started,
      on average, 66 hours after refractory status epilepticus onset with the goal of
      electroencephalography burst suppression, which was achieved, on average, 22.6
      hours later. Among patients failing midazolam, barbiturate infusion was effective
      in 65%. Inhaled anesthetics, ketamine, and hypothermia were generally used after
      prior therapy with midazolam and barbiturates had failed, usually several days
      after seizure onset. CONCLUSIONS: The data on intensive care treatment of
      pediatric refractory status epilepticus are of poor quality, yet they show a
      hierarchy in strategies: early midazolam, then barbiturates, and then trial of
      other anesthetic strategies. In addition, using a solely clinical endpoint for
      seizure control may be missing significant seizure burden in pediatric refractory
      status epilepticus.

PMID- 24901803
TI  - Higher doses of low-molecular-weight heparin (enoxaparin) are needed to achieve
      target anti-Xa concentrations in critically ill children*.
AB  - OBJECTIVES: To demonstrate that low-molecular-weight heparin (enoxaparin) can be
      used in critically ill pediatric patients to achieve target anti-factor Xa
      concentrations and determine appropriate dosing corrected for age and illness
      severity. DESIGN: Retrospective cohort study. SETTING: Single tertiary level
      PICU. PATIENTS: One hundred ninety-two children age 1 day through 18 years
      admitted to PICU undergoing every 12-hour enoxaparin therapy with at least one
      anti-factor Xa concentration obtained. Patients receiving renal replacement
      therapy or infants with corrected gestational age less than 37 weeks were
      excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected
      patient characteristics including age, weight, height/length, gender, corrected
      gestational age, illness severity markers, diagnosis, creatinine, enoxaparin dose
      and times of administration, anti-factor Xa concentrations, and collection times.
      Only 42% of critically ill children (80 of 192) and only 29% of children (9 of
      31) on inotropes achieved recommended target range of anti-factor Xa
      concentrations on initial recommended enoxaparin dosing (1.5 mg/kg/dose < 2 mo; 1
      mg/kg/dose > 2 mo), but 81% were ultimately within target range with dose
      titration. Increased enoxaparin dose was required to reach target concentrations
      in younger patients and those with worse illness severity as evidenced by
      concurrent use of inotropes, previous ICU admission, mechanical ventilation,
      cardiac surgery, and increased risk of mortality defined by severity-of-illness
      scores. CONCLUSIONS: Enoxaparin can be used to reach recommended target range of
      anti-factor Xa concentrations in the PICU patient. However, younger patients and
      patients with higher illness severity are less likely to achieve target
      concentrations using currently recommended dosing and may require higher doses of
      enoxaparin to reach target anti-factor Xa concentrations. Starting enoxaparin
      dose at least 1.3 mg/kg dosed every 12 hours for treatment of thromboembolic
      disease in critically ill patients aged 61 days to 1 year or those requiring
      inotropic support should be confirmed in prospective study.

PMID- 24901804
TI  - Antithrombin concentrate in pediatric patients requiring unfractionated heparin
      anticoagulation: a retrospective cohort study.
AB  - OBJECTIVE: To describe antithrombin levels, altered unfractionated heparin effect
      (anti-factor Xa activity and activated partial thromboplastin time), and adverse
      effects post administration of a single high dose of antithrombin concentrate.
      DESIGN: Retrospective review. PATIENTS: Infants and children with antithrombin
      levels less than 50% and a subtherapeutic unfractionated heparin effect. SETTING:
      Quaternary care children's hospital with a dedicated anticoagulation program.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A single high dose of
      antithrombin concentrate was administered. Antithrombin level, anti-factor Xa,
      and activated partial thromboplastin times were measured post antithrombin
      concentrate infusion and daily until stable. One hundred twenty-one patients
      received 246 doses of antithrombin. Patients were described using two cohorts
      based on the ability to obtain exact heparin doses. Cohort 1 included all
      patients between January 2004 and May 2008 when complete heparin dosing was
      unavailable. Cohort 2 included patients from May 2008 to May 2011 when heparin
      dose was available. Median age and weight were 3.7 months and 4.1 kg. Mean
      antithrombin concentrate dose was 222 IU/kg. Mean antithrombin level increased
      from 0.39 to 1.20 U/mL following antithrombin concentrate administration. In
      cohort 2, unfractionated heparin doses to achieve a target anti-factor Xa
      activity pre-post antithrombin concentrate were 28 and 19 U/kg/hr, respectively,
      for children 12 months old or younger and 25 and 19 U/kg/hr, respectively, for
      children older than 12 months. There were no hemorrhagic, thrombotic, or allergic
      events within 1 week of antithrombin concentrate administration. CONCLUSIONS:
      This is the largest study of antithrombin concentrate evaluation in children.
      Administration of antithrombin concentrate increases anti-factor Xa activity with
      lower administered unfractionated heparin doses.

PMID- 24901805
TI  - Intramolecular charge transfer photoemission of a silicon-based copolymer
      containing carbazole and divinylbenzene chromophores. Electron transfer across
      silicon bridges.
AB  - A new copolymer consisting of N-isopropylcarbazole/dimethylsilylene
      bridge/divinylbenzene units was synthesized and characterized. Dual fluorescence
      was observed in this copolymer in polar solvents. The absence of the second band
      at the lower transition energy of the two emission maxima in nonpolar solvents
      and the quantitative correlation of the lower-energy emission band maxima with
      solvent polarity indicate that the lower-energy emission band arises from an
      intramolecular charge transfer (ICT) state. A series of model compounds was
      synthesized to investigate the source of the charge transfer. It was found that
      the Si-bridged dyad with a single N-isopropylcarbazole and a single
      divinylbenzene was the minimum structure necessary to observe dual luminescence.
      The lack of dual luminescence in low-temperature glasses indicates that the ICT
      requires a conformation change in the copolymer. Analogous behavior in the Si
      bridged dyad suggests that the ICT in the copolymer is across the silicon bridge.
      Results from time-resolved luminescence measurements with picosecond and
      subnanosecond excitation were used to support the thesis that twisted charge
      transfer states are the likely source of the observed dual luminescence. 

PMID- 24901806
TI  - Estimating ground-level PM2.5 in China using satellite remote sensing.
AB  - Estimating ground-level PM2.5 from satellite-derived aerosol optical depth (AOD)
      using a spatial statistical model is a promising new method to evaluate the
      spatial and temporal characteristics of PM2.5 exposure in a large geographic
      region. However, studies outside North America have been limited due to the lack
      of ground PM2.5 measurements to calibrate the model. Taking advantage of the
      newly established national monitoring network, we developed a national-scale
      geographically weighted regression (GWR) model to estimate daily PM2.5
      concentrations in China with fused satellite AOD as the primary predictor. The
      results showed that the meteorological and land use information can greatly
      improve model performance. The overall cross-validation (CV) R(2) is 0.64 and
      root mean squared prediction error (RMSE) is 32.98 MUg/m(3). The mean prediction
      error (MPE) of the predicted annual PM2.5 is 8.28 MUg/m(3). Our predicted annual
      PM2.5 concentrations indicated that over 96% of the Chinese population lives in
      areas that exceed the Chinese National Ambient Air Quality Standard (CNAAQS)
      Level 2 standard. Our results also confirmed satellite-derived AOD in conjunction
      with meteorological fields and land use information can be successfully applied
      to extend the ground PM2.5 monitoring network in China. 

PMID- 24901808
TI  - Violaceous and ulcerated plaque following a cesarean section-quiz case.

PMID- 24901807
TI  - The role of ubiquitin-binding domains in human pathophysiology.
AB  - Ubiquitination, a fundamental post-translational modification (PTM) resulting in
      the covalent attachment of ubiquitin (Ub) to a target protein, is currently
      implicated in several key cellular processes. Although ubiquitination was
      initially associated with protein degradation, it is becoming increasingly
      evident that proteins labeled with polyUb chains of specific topology and length
      are activated in an ever-expanding repertoire of specific cellular processes. In
      addition to their involvement in the classical protein degradation pathways they
      are involved in DNA repair, kinase regulation and nuclear factor-kappaB (NF
      kappaB) signaling. The sorting and processing of distinct Ub signals is mediated
      by small protein motifs, known as Ub-binding domains (UBDs), which are found in
      proteins that execute disparate biological functions. The involvement of UBDs in
      several biological pathways has been revealed by several studies which have
      highlighted the vital role of UBDs in cellular homeostasis. Importantly,
      functional impairment of UBDs in key regulatory pathways has been related to the
      development of pathophysiological conditions, including immune disorders and
      cancer. In this review, we present an up-to-date account of the crucial role of
      UBDs and their functions, with a special emphasis on their functional impairment
      in key biological pathways and the pathogenesis of several human diseases. The
      still under-investigated topic of Ub-UBD interactions as a target for developing
      novel therapeutic strategies against many diseases is also discussed.

PMID- 24901809
TI  - Ingestion of a moderately high caffeine dose before exercise increases
      postexercise energy expenditure.
AB  - Caffeine is an ergogenic aid widely used before and during prolonged exercise.
      Due to its prolonged biological half-life caffeine effects could remain after
      exercise. We aimed to investigate the metabolic, respiratory, and cardiovascular
      postexercise responses to preexercise graded caffeine ingestion. Twelve
      aerobically trained subjects (mean VO2max = 54 +/- 7 ml . min-1 . kg-1) cycled
      for 60-min at 75% VO2max after ingesting placebo (0 mg of caffeine per kg of body
      weight) or 0.5, 1.5, 3.0 and 4.5 mg . kg-1 on five occasions. During the 3 hr
      postexercise, heart rate, blood pressure, glucose, lactate, and fatty acids were
      analyzed. None of these variables were statistically affected by preexercise
      caffeine ingestion between 0.5 and 4.5 mg . kg-1. However, ingestion of 4.5 mg .
      kg-1 of caffeine raised postexercise energy expenditure 15% above placebo (233 +/
      58 vs. 202 +/- 49 kcal/3 hr; p < .05). Ventilation and tidal volume were
      elevated after the 4.5 mg . kg-1 caffeine dose above placebo (9.2 +/- 2.5 L . min
      1 and 0.67 +/- 0.29 L . breath-1 vs. 7.8 +/- 1.5 L . min-1 and 0.56 +/- 0.20 L .
      breath-1, respectively; p < .05). Ventilation correlated with tidal volume (r =
      .45; p < .05) and energy expenditure (r = .72; p < .05). In summary, preexercise
      ingestion of ergogenic caffeine doses do not alter postexercise cardiovascular
      responses. However, ingestion of 4.5 mg . kg-1 of caffeine raises 3-hr
      postexercise energy expenditure (i.e., 31 kcal) likely through increased energy
      cost of ventilation.

PMID- 24901810
TI  - Neurons and tumor suppressors.
AB  - Neurons choose growth pathways with half hearted reluctance, behavior that may be
      appropriate to maintain fixed long lasting connections but not to regenerate
      them. We now recognize that intrinsic brakes on regrowth are widely expressed in
      these hesitant neurons and include classical tumor suppressor molecules. Here, we
      review how two brakes, PTEN (phosphatase and tensin homolog deleted on chromosome
      10) and retinoblastoma emerge as new and exciting knockdown targets to enhance
      neuron plasticity and improve outcome from damage or disease. 

PMID- 24901811
TI  - Image of the month-quiz case.

PMID- 24901812
TI  - Image of the month-quiz case.

PMID- 24901813
TI  - The improvement of quality of life a indication for elective surgery in elderly
      patients with minimally symptomatic inguinal hernia.
AB  - AIM: Effectiveness of surgery on quality of life in elderly affected by minimally
      symptomatic inguinal hernia. MATERIAL OF STUDY: Forty male patients aging over 75
      years affected by minimally symptomatic inguinal hernia were included. In the
      first group were allocated 15 patients who refused hernioplasty; in the second
      were included 25 patients who underwent early elective hernioplasty using an high
      density polypropylene mesh under local anesthesia. The SF-36 questionnaire was
      administered to all patients at the time of enrollment and 6 months after.
      RESULTS: All 8 domains of SF-36 and his related two comprhensive index, Mental
      Component Summary and Physical Component Summary scores, improved 6 months after
      surgery in patients of the second group. No significant differences were detected
      in the first group. DISCUSSION: There is no scientific evidence concerning early
      repair or watchful waiting strategy for elderly with minimally symptomatic
      inguinal hernia. in the last years, the evaluation of quality of life have a
      central role in the decision making of disease. CONCLUSION: Improvement of
      quality of life in elderly with minimally symptomatic inguinal hernia underwent
      to early hernia repair hernioplasty could represents a further indication for
      elective hernia repair.

PMID- 24901814
TI  - Fluorescence imaging for the detection of early neoplasia in Barrett's esophagus:
      old looks or new vision?
AB  - Early neoplasia arising from Barrett's esophagus is often small, focally
      distributed and endoscopically poorly visible, and random four-quandrant biopsies
      may easily miss early lesions. Advanced imaging techniques, such as
      (auto)fluorescence-based modalities, aim to increase the detection rate of early
      lesions or the yield of random biopsies. Fluorescence-based light-tissue
      interaction has been designed successfully in point-probe differentiating
      spectroscopy systems or integrated into wide-field endoscopic systems such as
      autofluorescence imaging (AFI). In this review, we discuss the most recent
      advances in fluorescence spectroscopy and imaging for detecting early Barrett's
      neoplasia. A spectroscopy probe, integrated into regular biopsy forceps, was
      shown to offer decent discriminatory capabilities, while ensuring spot-on
      correlation between the measured area and the corresponding histology. With this
      tool, surveillance endoscopy with random biopsies may become more efficient and
      sensitive. AFI was shown to increase the targeted detection of early neoplasia.
      However, random biopsies could compensate for this effect. The clinical impact of
      AFI on the diagnosis and the treatment of early neoplasia is limited, and yet AFI
      may offer a novel approach in biomarker-based risk-stratification models.
      Moreover, in combination with new, readily available contrast agents such as
      fluorescent lectins, fluorescence imaging may receive renewed interest. 

PMID- 24901815
TI  - The safety of a strict wire-guided dilation protocol for eosinophilic
      esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated
      disease seen in an increasing number of young adults. Solid food dysphagia is the
      most common presenting symptom, and food impactions are not uncommon because of
      stricturing and decreased compliance of the esophagus. Although esophageal
      dilation is effective in managing patients with EoE, it needs to be performed
      cautiously, given a perceived higher rate of perforation. AIM: The aim of this
      study was to evaluate the safety of a strict wire-guided dilation protocol used
      in patients with EoE. METHODS: A retrospective review was performed to identify
      patients treated for EoE by a single physician (K.M.) over a 9-year period at
      UPMC. Medical records were reviewed to obtain information on demographic,
      clinical, and outcome data. Newly diagnosed and previously known EoE patients
      (biopsy proven) who underwent serial wire-guided bougie dilation were included in
      this study. All procedures were performed using monitored anesthesia care. On the
      basis of the initial endoscopic inspection, a bougie size was chosen that was
      subjectively considered to approximate the size of the esophageal lumen diameter.
      Fluoroscopy was used for safe guide wire placement if the endoscope could not
      traverse the stricture. After each bougie passage, the esophagus was reintubated
      with the endoscope to assess for mucosal tears. Serial dilation by 1 mm
      increments was continued until a small to moderate mucosal tear was seen,
      whereupon the procedure was terminated. For an index endoscopy for suspected EoE,
      biopsies were also taken to confirm the diagnosis. RESULTS: Thirty patients were
      identified, mean age 33 years, 90% men. Solid food dysphagia was present in all.
      Twenty-seven patients (90%) were diagnosed with EoE during the index dilation;
      17% underwent dilation for known, but symptomatic EoE. The median initial bougie
      size was 11. The median final bougie size was 15 mm; 24 patients (80%) had
      resultant mucosal tears. One patient complained of postprocedure chest pain
      requiring opioids. There were no perforations or hospitalizations. After
      dilation, patients were placed on swallowed fluticasone for 6 weeks (87%),
      maintenance montelukast (90%), or a prednisone taper (7%). Six patients (20%)
      underwent repeat dilation for recurrent dysphagia. All except one of these
      patients were on medical therapy for EoE. CONCLUSION: Serial wire-guided dilation
      guided by repeated endoscopic inspection is safe in patients with EoE. Caution
      should be exercised when choosing the initial dilator size.

PMID- 24901816
TI  - The accuracy of flexible spectral imaging colour enhancement for the diagnosis of
      gastric intestinal metaplasia: do we still need histology to select individuals
      at risk for adenocarcinoma?
AB  - BACKGROUND: Targeting biopsies on the basis of visual recognition of mucosal
      changes in the stomach instead of the currently accepted random biopsy sampling
      may be attractive. AIM: The aim of this study was to evaluate the accuracy of
      endoscopic findings using flexible spectral imaging colour enhancement (FICE) for
      intestinal metaplasia (IM) in the gastric mucosa. METHODS: A consecutive cohort
      of 126 individuals aged over 50 years (27% men) was subjected to upper endoscopy
      using FICE. Histological assessment (per patient and per biopsy) was considered
      the gold standard to accuracy estimates. RESULTS: Histological assessment
      revealed IM in 50% of the individuals [OLGIM (operative link on gastric
      intestinal metaplasia assessment) stages I-IV]. Overall, endoscopy presented
      sensitivities, specificities, positive likelihood ratio, negative likelihood
      ratio and accuracies per patient of 60% [95% confidence interval (95% CI) 48-72],
      87% (95% CI 79-95), 4.7 (95% CI 2.4-93), 0.45 (95% CI 0.33-0.62) and 74% (95% CI
      0.66-0.82), respectively, for IM diagnosis and 71% (95% CI 37-100), 87% (95% CI
      79-95), 5.6 (95% CI 2.5-12.5), 0.32 (95% CI 0.10-1.0) and 86% (95% CI 77-94),
      respectively, for selecting individuals with OLGIM (III-IV). The proportions of
      agreement (and kappa values) for IM in the antrum and the corpus were 75% (0.37)
      and 81% (0.19), respectively. CONCLUSION: FICE endoscopy yielded favourable
      results in the endoscopic diagnosis of IM of the gastric mucosa, and this is a
      very practical and easy method to use in daily clinical practice for unselected
      patients. Our study demonstrated a good specificity for FICE endoscopy to detect
      IM in the stomach. Further improvement in disseminating and training of this
      assessment is required to improve the reliability.

PMID- 24901817
TI  - Gastric mucin expression in first-degree relatives of gastric cancer patients.
AB  - OBJECTIVES: There are currently no accepted clinical guidelines for the
      surveillance of first-degree relatives (FDRs) of gastric cancer patients. The
      existence of intestinal metaplasia, as well as altered mucin expression, might be
      associated with an increased risk for gastric cancer. In the present study we
      aimed to investigate the mucin phenotype of individuals with a family history of
      gastric cancer. METHODS: We included FDRs of gastric cancer patients. Individuals
      with functional chest pain served as controls. Upper endoscopy including
      extensive biopsy according to the Olga protocol was performed.
      Immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 was performed. Sera
      were assayed for pepsinogen I and II. Helicobacter status was determined through
      Giemsa staining and serological tests. RESULTS: Forty FDRs and eight controls
      were included; the mean age was 46.7 +/- 12.0 years. In both the study group and
      the control group there were no gross endoscopic findings and no histological
      evidence of intestinal metaplasia. Superficial MUC1 expression was significantly
      increased in the study group (47.5 vs. 0%; P=0.01). There was no difference in
      the expression of deep MUC1, MUC2, MUC5AC, or MUC6 between the groups, nor was
      there a difference in pepsinogen I/II levels or Helicobacter pylori exposure
      (35.0 vs. 25.0%; P=0.46). CONCLUSION: Despite normal appearing mucosa and the
      absence of intestinal metaplasia according to histological analysis, FDRs of
      gastric cancer patients show increased expression of MUC1, which may serve as a
      predictor of future intestinal metaplasia, dysplasia, and cancer. Further studies
      are needed to verify these findings and their implications.

PMID- 24901818
TI  - Increased pulse wave velocity and relationship with inflammation, insulin, and
      insulin resistance in inflammatory bowel disease.
AB  - OBJECTIVE: Both ulcerative colitis and Crohn's disease are forms of inflammatory
      bowel disease (IBD), which is characterized by chronic, progressive inflammation
      of the gastrointestinal tract. Recent studies have shed new light on the
      importance of inflammation in the pathogenesis of arterial stiffness. AIM: This
      study aimed to evaluate the relationship between pulse wave velocity (PWV)
      measurement and biochemical parameters in inactive and active IBD patients
      without cardiovascular risk factors and perform a comparison with the control
      group. MATERIALS AND METHODS: We enrolled 102 IBD patients without cardiovascular
      risk factors and 74 matched controls, and evaluated each patient in active and
      inactive disease periods. All patients completed a standard questionnaire form
      and we assessed various laboratory parameters. We carried out vascular
      measurements using a Mobil-O-Graph 24-h pulse wave analysis monitor, an automatic
      oscillometric device. RESULTS: Although cardiovascular risk factors, such as
      total cholesterol and low-density lipoprotein cholesterol, were significantly
      lower (P<0.05) in IBD patients than the controls, 24 h, day and night PWV values,
      erythrocyte sedimentation rate, C-reactive protein, insulin, homeostasis model
      assessment of insulin resistance, and homocysteine were higher in patients with
      active and inactive IBD than the controls (P<0.05). Multiple linear regression
      analysis showed that PWV was correlated positively with age and duration of IBD.
      CONCLUSION: This study showed increased PWV, homocysteine, erythrocyte
      sedimentation rate, C-reactive protein, insulin, and homeostasis model assessment
      of insulin resistance in patients with active and inactive IBD and provides
      evidence of the potential contribution of inflammation and inflammation-related
      factors toward arterial stiffening independent from conventional cardiovascular
      risk factors.

PMID- 24901819
TI  - Serum antibodies to microbial antigens for Crohn's disease progression: a meta
      analysis.
AB  - OBJECTIVES: This meta-analysis evaluated the stratification powers of four well
      studied serum antibodies to microbial antigens [ASCA (anti-Saccharomyces
      cerevisiae), anti-OmpC (anti-outer-membrane protein C), anti-I2 (anti-Pseudomonas
      fluorescens-associated sequence I2), and anti-CBir1 (anti-bacterial flagellin)]
      in characterizing progression of Crohn's disease (CD). METHODS: Pooled
      sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence
      intervals (CI) for individual antibodies and antibody combination were used to
      evaluate and compare their stratification powers for CD-related complications and
      the need for surgery. RESULTS: Eleven studies were included in this meta
      analysis. In terms of the outcomes for CD complication and surgery, ASCA had the
      highest sensitivities at 0.66 (CI 0.63-0.69) for complications and 0.66 (CI 0.63
      0.68) for surgery, whereas anti-OmpC had the highest specificities at 0.83 (CI
      0.80-0.85) for complications and 0.81 (CI 0.79-0.83) for surgery. Anti-OmpC had
      the highest DORs at 2.61 (CI 2.16-3.15) for complications and 2.93 (CI 2.48-3.47)
      for surgery, and a combination of at least two antibodies presented pooled DORs
      at 2.93 (CI 2.42-3.56) for complications and 3.39 (CI 2.73-4.20) for surgery,
      superior to any single antibody. CONCLUSION: Anti-OmpC had the highest
      stratification power among the four antibodies screened for the risk of both
      complications and surgery in CD patients, and the power became stronger when
      antibodies were assessed in combination.

PMID- 24901820
TI  - Decreased parasympathetic activity in patients with functional dyspepsia.
AB  - OBJECTIVE: Functional dyspepsia (FD) can be described as the presence of symptoms
      such as bothersome postprandial fullness, early satiation, epigastric pain, and
      burning without any evidence of structural disease. The aim of this study was to
      evaluate the autonomic nervous system using heart rate variability (HRV) in
      patients with postprandial distress syndrome and epigastric pain syndrome.
      PATIENTS AND METHODS: The study population included 64 consecutive patients with
      a diagnosis of FD and 62 age-matched and sex-matched healthy control individuals
      with no clinical evidence of gastrointestinal, systemic, or cardiovascular
      diseases. All patients underwent upper gastrointestinal endoscopy and 24 h Holter
      monitoring. RESULTS: There were 30 patients with postprandial distress syndrome
      and 34 with epigastric pain syndrome. Twenty-four hour square root of the mean
      squared differences of the successive normal to normal intervals (RMSSD) (30.5 +/
      12.4, 35.8 +/- 13.9; P=0.047), 24 h proportion derived by dividing the number of
      interval differences of successive normal to normal intervals greater than 50 ms
      (PNN50) (9.8 +/- 3.9, 14.1 +/- 7.3; P=0.017), daytime PNN50 (6.8 +/- 1.6, 18.4 +/
      13.8; P<0.001), night SD of the normal to normal intervals (SDNN) (111.4 +/-
      39.9, 133.4 +/- 29.8; P=0.001), and night RMSSD (31.7 +/- 12.4, 38.2 +/- 17.5;
      P=0.019) were significantly lower in patients with FD than controls. Other HRV
      parameters were not significantly different between the two groups. Changes in
      these parameters showed a decreased parasympathetic tone and discordance in
      sympathovagal activity in FD. CONCLUSION: Our study showed decreased
      parasympathetic activity in the patients with FD. Further studies are required to
      evaluate the significance of HRV parameters and to clarify the mechanism of
      decreased parasympathetic activity in patients with FD.

PMID- 24901821
TI  - VX-222, a non-nucleoside NS5B polymerase inhibitor, in telaprevir-based regimens
      for genotype 1 hepatitis C virus infection.
AB  - OBJECTIVE: To investigate in this phase 2a study (ZENITH) the safety,
      tolerability, and antiviral activity of VX-222, a selective, non-nucleoside
      inhibitor of hepatitis C virus (HCV) NS5B polymerase, combined with various
      telaprevir-based regimens for treatment of genotype 1 HCV. METHODS: In total, 152
      treatment-naive patients received VX-222+telaprevir ('DUAL' regimen; n=47), with
      ribavirin ('TRIPLE' regimen; n=46), or with peginterferon+ribavirin ('QUAD'
      regimen; n=59) for 12 weeks. Patients with detectable HCV RNA at weeks 2 and/or 8
      received peginterferon+ribavirin for 24 (DUAL and TRIPLE) or 12 (QUAD) additional
      weeks. RESULTS: VX-222 (100 or 400 mg twice daily) was well tolerated, with an
      increased rate of gastrointestinal adverse events observed with the higher dose.
      Across VX-222 400-mg twice-daily regimens, the QUAD was associated with the
      highest frequency of grade 3/4 adverse events. The DUAL was discontinued because
      of high viral breakthrough before week 12. Sustained virologic response (SVR) 24
      weeks after end of treatment (SVR24), including patients treated with 12 or 24
      additional weeks of peginterferon+ribavirin, was 67% for TRIPLE (VX-222 400 mg
      twice daily) and 79 and 90% for QUAD (VX-222 100 and 400 mg twice daily,
      respectively). CONCLUSION: These results provide valuable information regarding
      the safety, tolerability, and efficacy of telaprevir combined with a non
      nucleoside polymerase inhibitor, as dual therapy or with ribavirin without or
      with peginterferon. Telaprevir and VX-222, alone or with ribavirin without or
      with peginterferon, were generally well tolerated, with improved tolerability
      without peginterferon. SVR24 rates achieved with TRIPLE and QUAD regimens
      containing telaprevir and VX-222 were comparable to those observed with
      telaprevir-based therapy.

PMID- 24901822
TI  - First-line monotherapies of tenofovir and entecavir have comparable efficacies in
      hepatitis B treatment.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a health problem worldwide.
      Current treatment options for chronic hepatitis B (CHB) are nucleoside or
      nucleotide analogues and pegylated interferons. Tenofovir and entecavir are much
      more commonly used as they have better efficacy, tolerability, and high genetic
      barriers to resistance. AIM: The aim of this study was to assess the efficacies
      of tenofovir and entecavir in previously untreated CHB patients in a treatment
      cohort. PATIENTS AND METHODS: We included CHB patients in a cohort including
      previously untreated HBeAg-positive and HBeAg-negative patients from 10 centers
      in Istanbul, Turkey. The patients were compared in terms of baseline
      characteristics, decrease in alanine transaminase (ALT), decrease in HBV-DNA to
      undetectable levels, HBeAg loss and anti-HBe development (among baseline HBeAg
      positive patients), interventions to therapy because of lack of efficacy, side
      effects, severe side effects, and side effects that required change in treatment.
      RESULTS: The study included 121 patients who were administered tenofovir and 130
      patients who were administered entecavir. The majority of patients were men, with
      mild to moderate histology in both treatment groups. The mean duration of follow
      up was 18 and 20 months for tenofovir and entecavir, respectively. Patients
      receiving both drugs showed comparable rates of HBeAg loss, rates of undetectable
      HBV-DNA levels, rates of ALT normalization, ALT decrease, and decrease in HBV
      DNA. Both drugs were well tolerated. CONCLUSION: This study shows that although
      the baseline characteristics did not match, tenofovir and entecavir sustained
      comparable virological efficacies. More patients discontinued entecavir during
      follow-up. Both drugs provided effective viral control, with few side effects.

PMID- 24901823
TI  - Obstructive component analysis of radioactive stents and common plastic stents in
      the bile duct.
AB  - BACKGROUND: Endoscopic placement of a iodine-125 radioactive stent is useful to
      treat obstructive jaundice with unresectable periampullary tumors. This study
      aimed to retrospectively evaluate the obstructive component of biliary
      radioactive stents and discuss the different obstructive mechanism with common
      plastic stents. PATIENTS AND METHODS: Twenty consecutive patients with malignant
      obstruction underwent insertion of stents into the common bile duct, including 10
      radioactive stents and 10 polyethylene stents. The radioactive stents were
      withdrawn after ~3 months or earlier if clinical signs suggested stent clogging.
      Polyethylene stents were withdrawn after physical signs suggested stent clogging.
      Bacteriologic analyses included identification of aerobic and anaerobic bacteria.
      Stent surfaces were observed by scanning electron microscopy. Stent deposition
      was identified by Fourier-transformed infrared spectroscopy and pyrolysis
      derivatization/gas chromatography/mass spectrometry. RESULTS: Radioactive stent
      group and polyethylene stent group stents were placed for 86 days (interquartile
      range 62, 114) and 146 days (interquartile range 105, 181) respectively. The
      placement duration of the two types of stents was statistically significant. A
      variety of microorganisms were cultured from the stent deposits. Scanning
      electron microscope images showed a thicker necrotic layer on the external
      surface of polyethylene stent than the radioactive stent group. The proportions
      of obstructive components in each stent were different, but none of them were
      statistically significant. Necrotic tumor tissue was found in the radioactive
      stent group. CONCLUSION: Similar clogging events occurred in both radioactive
      stents and polyethylene stents. The median duration time of the radioactive stent
      was shorter, probably because of the smaller inner diameter, and the radioactive
      seeds exerted no beneficial effect in inhibiting microorganisms.

PMID- 24901824
TI  - A distinct pattern of disease-associated single nucleotide polymorphisms in IBD
      risk genes in a family with Crohn's disease.
AB  - Recent studies have identified more than 160 inflammatory bowel disease
      susceptibility loci and provided evidence for genetic heritability in disease
      pathogenesis. Here we describe a case of a 47-year-old White woman suffering from
      Crohn's disease (CD), who had four children, two with CD and two with a factor V
      Leiden variation. We analysed the presence of single nucleotide polymorphisms in
      several CD susceptibility genes. SNP analysis was carried out using commercially
      available assays. The female CD patient had a positive inflammatory bowel disease
      family history. All of the patients had a mild disease course, without fistulae
      or symptomatic stenosis. The patient was heterozygous for risk variants of the
      genes encoding nucleotide oligomerization domain 2 (NOD2) and Toll-like receptor
      5 (TLR5) and a homozygous carrier of both of the identified protein tyrosine
      phosphatase nonreceptor type 2 (PTPN2) risk alleles. The CD-affected daughter
      carried heterozygous risk alleles of the genes encoding TLR5, NOD2 and PTPN2. The
      son, with the earliest onset of disease in the family at the age of 12 years, was
      heterozygous for risk alleles of autophagy 16 like 1 (ATG16L1), TLR5, NOD2 and
      PTPN2. This study reports an interesting pattern of CD-associated single
      nucleotide polymorphisms in a family with CD. This report clearly supports the
      observation that genetic variations, especially in genes associated with the
      innate immune system, contribute to disease onset. 

PMID- 24901825
TI  - Celiac disease and gastric hyperplastic polyps: a case series of an uncommon
      association.
AB  - Gastric polypoid lesions are found in ~1-4% of patients who undergo
      esophagogastroduodenoscopy. The hyperplastic lesions are considered non
      neoplastic polyps that are distributed randomly in the stomach and they are
      usually related to chronic gastritis as a result of the exaggerated mucosal
      healing response. Although several conditions have been associated with celiac
      disease (CD), such as thyroiditis, Addison's disease, type 1 diabetes mellitus,
      and autoimmune hepatitis, the association with gastric polyps is rare. In this
      case series, we present seven newly diagnosed patients (six women) with CD and
      hyperplastic gastric polyps. Helicobacter pylori infection was ruled out through
      histology in all the patients and two out of seven had a history of occasional
      proton pump inhibitor use. An unusual association was found between CD and
      hyperplastic polyps in this case series. 

PMID- 24901826
TI  - New onset pulmonary hypertension in a patient with primary biliary cirrhosis
      postorthotopic liver transplant.

PMID- 24901827
TI  - An Italian perspective: studying the cost-effectiveness of sofosbuvir before
      completion of national price negotiations.

PMID- 24901828
TI  - Is hematocrit really associated with fibrosis in patients with nonalcoholic
      steatohepatitis?

PMID- 24901829
TI  - Is high RDW really closely associated with NAFLD?

PMID- 24901830
TI  - An important issue in the calculation of PGAA for the diagnosis of fibrosis stage
      in patients with alcoholic liver disease.

PMID- 24901832
TI  - Synthesis and evaluation of a series of novel asymmetrical curcumin analogs for
      the treatment of inflammation.
AB  - Curcumin has been reported to possess multiple bioactivities, such as
      antioxidant, anticancer, and anti-inflammatory properties, however the clinical
      application of curcumin has been significantly limited by its instability and
      poor metabolism. Modification of curcumin has led to discovery and development of
      lots of novel therapeutic candidates. In recent years acute and chronic
      inflammation has been the focus of numerous studies in various diseases. Here, we
      synthesized a series of asymmetrical curcumin analogs with high in vitro chemical
      stability, and their anti-inflammatory activity was evaluated in LPS-stimulated
      macrophages. According to the bio-screening results and QSAR analysis, these
      analogs exhibited potent activities against LPS-induced TNF-alpha and IL-6
      release. Among the analogs of the potent anti-inflammatory activity, compounds
      3b8 and 3b9 exhibited significant protection and possess enhanced anti
      inflammatory activity thereby attenuated the LPS-induced septic death in mice. 

PMID- 24901833
TI  - Two new chemical constituents from the stem bark of Garcinia mangostana.
AB  - A detailed chemical study on the ethyl acetate and methanol extracts of the stem
      bark of Garcinia mangostana resulted in the successful isolation of one new
      prenylated xanthone, mangaxanthone B (1), one new benzophenone, mangaphenone (2),
      and two known xanthones, mangostanin (3) and mangostenol (4). The structures of
      these compounds were elucidated through analysis of their spectroscopic data
      obtained using 1D and 2D NMR and MS techniques. 

PMID- 24901834
TI  - Montmorillonite clay-promoted, solvent-free cross-aldol condensations under
      focused microwave irradiation.
AB  - An environmentally benign, clean and general protocol was developed for the
      synthesis of aryl and heteroaryl trans-chalcones. This method involved solvent
      free reaction conditions under microwave irradiation in the presence of a clay
      based catalyst, and afforded the target compounds in good yields and short
      reaction times. Furthermore, the same conditions allowed the synthesis of
      symmetrical, diarylmethylene-alpha,beta-unsaturated ketones from aromatic
      aldehydes and ketones. 

PMID- 24901836
TI  - Substituent effects on spin state in a series of mononuclear manganese(III)
      complexes with hexadentate Schiff-Base ligands.
AB  - Eleven new mononuclear manganese(III) complexes prepared from two hexadentate
      ligands, L1 and L2, with different degrees of steric bulk in the substituents are
      reported. L1 and L2 are Schiff bases resulting from condensation of N,N'-bis(3
      aminopropyl)ethylenediamine with 3-methoxy-2-hydroxybenzaldehyde and 3-ethoxy-2
      hydroxybenzaldehyde respectively, and are members of a ligand series we have
      abbreviated as R-Sal2323 to indicate the 323 alkyl connectivity in the starting
      tetraamine and the substitution (R) on the phenolate ring. L1 hosts a methoxy
      substituent on both phenolate rings, while L2 bears a larger ethoxy group in the
      same position. Structural and magnetic properties are reported in comparison with
      those of a previously reported analogue with L1, namely, [MnL1]NO3, (1e). The
      BPh4(-) and PF6(-) complexes [MnL1]BPh4, (1a), [MnL2]BPh4, (2a), [MnL1]PF6,
      (1b'), and [MnL2]PF6, (2b), with both ligands L1 and L2, remain high-spin (HS)
      over the measured temperature range. However, the monohydrate of (1b')
      [MnL1]PF6.H2O, (1b), shows gradual spin-crossover (SCO), as do the ClO4(-), BF4(
      ), and NO3(-) complexes [MnL1]ClO4.H2O, (1c), [MnL2]ClO4, (2c), [MnL1]BF4.H2O,
      (1d), [MnL2]BF4.0.4H2O, (2d), [MnL1]NO3, (1e), and [MnL2]NO3.EtOH, (2e). The
      three complexes formed with ethoxy-substituted ligand L2 all show a higher T1/2
      than the analogous complexes with methoxy-substituted ligand L1. Analysis of
      distortion parameters shows that complexes formed with the bulkier ligand L2
      exhibit more deformation from perfect octahedral geometry, leading to a higher
      T1/2 in the SCO examples, where T1/2 is the temperature where the spin state is
      50% high spin and 50% low spin. Spin state assignment in the solid state is shown
      to be solvate-dependent for complexes (1b) and (2e), and room temperature UV
      visible and NMR spectra indicate a solution-state spin assignment intermediate
      between fully HS and fully low spin in 10 complexes, (1a)-(1e) and (2a)-(2e). 

PMID- 24901835
TI  - Are in vitro methods for the detection of endocrine potentials in the aquatic
      environment predictive for in vivo effects? Outcomes of the Projects
      SchussenAktiv and SchussenAktivplus in the Lake Constance Area, Germany.
AB  - Many studies about endocrine pollution in the aquatic environment reveal changes
      in the reproduction system of biota. We analysed endocrine activities in two
      rivers in Southern Germany using three approaches: (1) chemical analyses, (2) in
      vitro bioassays, and (3) in vivo investigations in fish and snails. Chemical
      analyses were based on gas chromatography coupled with mass spectrometry. For in
      vitro analyses of endocrine potentials in water, sediment, and waste water
      samples, we used the E-screen assay (human breast cancer cells MCF-7) and
      reporter gene assays (human cell line HeLa-9903 and MDA-kb2). In addition, we
      performed reproduction tests with the freshwater mudsnail Potamopyrgus
      antipodarum to analyse water and sediment samples. We exposed juvenile brown
      trout (Salmo trutta f. fario) to water downstream of a wastewater outfall
      (Schussen River) or to water from a reference site (Argen River) to investigate
      the vitellogenin production. Furthermore, two feral fish species, chub (Leuciscus
      cephalus) and spirlin (Alburnoides bipunctatus), were caught in both rivers to
      determine their gonadal maturity and the gonadosomatic index. Chemical analyses
      provided only little information about endocrine active substances, whereas the
      in vitro assays revealed endocrine potentials in most of the samples. In addition
      to endocrine potentials, we also observed toxic potentials (E-screen/reproduction
      test) in waste water samples, which could interfere with and camouflage endocrine
      effects. The results of our in vivo tests were mostly in line with the results of
      the in vitro assays and revealed a consistent reproduction-disrupting
      (reproduction tests) and an occasional endocrine action (vitellogenin levels) in
      both investigated rivers, with more pronounced effects for the Schussen river
      (e.g. a lower gonadosomatic index). We were able to show that biological in vitro
      assays for endocrine potentials in natural stream water reasonably reflect
      reproduction and endocrine disruption observed in snails and field-exposed fish,
      respectively. 

PMID- 24901837
TI  - Netrins and Wnts function redundantly to regulate antero-posterior and dorso
      ventral guidance in C. elegans.
AB  - Guided migrations of cells and developing axons along the dorso-ventral (D/V) and
      antero-posterior (A/P) body axes govern tissue patterning and neuronal
      connections. In C. elegans, as in vertebrates, D/V and A/P graded distributions
      of UNC-6/Netrin and Wnts, respectively, provide instructive polarity information
      to guide cells and axons migrating along these axes. By means of a comprehensive
      genetic analysis, we found that simultaneous loss of Wnt and Netrin signaling
      components reveals previously unknown and unexpected redundant roles for Wnt and
      Netrin signaling pathways in both D/V and A/P guidance of migrating cells and
      axons in C. elegans, as well as in processes essential for organ function and
      viability. Thus, in addition to providing polarity information for migration
      along the axis of their gradation, Wnts and Netrin are each able to guide
      migrations orthogonal to the axis of their gradation. Netrin signaling not only
      functions redundantly with some Wnts, but also counterbalances the effects of
      others to guide A/P migrations, while the involvement of Wnt signaling in D/V
      guidance identifies Wnt signaling as one of the long sought mechanisms that
      functions in parallel to Netrin signaling to promote D/V guidance of cells and
      axons. These findings provide new avenues for deciphering how A/P and D/V
      guidance signals are integrated within the cell to establish polarity in multiple
      biological processes, and implicate broader roles for Netrin and Wnt signaling-
      roles that are currently masked due to prevalent redundancy.

PMID- 24901838
TI  - Internal Delorme vs. STARR procedure for correction of obstructed defecation from
      rectocele and rectal intussusception.
AB  - PURPOSE: "Outlet obstruction" is a complex functional disorder compelling
      patients to exhausting uneffective attempts to void. This study was designed to
      compare the effectiveness and a safety of the endorectal proctopexy (internal
      Delorme) vs STARR procedure in two groups of patients. METHODS: A total of 66
      patients with rectocele and associated mucosal prolapse or anorectal
      intussusception between January 2006 and June 2010 were randomly assigned to
      Group # 1 Endorectal proctopexy with levatorplasty (ERPP) and Group # 2 STARR.
      Patients were assessed one week, six and twelve months after the operation.
      Operative time, postoperative pain, day of discharge and late complications was
      recorded. The time of recovery of work was also assessed. The continence score
      was updated with a constipation questionnaire. Quality of life after the
      operation and the overall grade of satisfaction were assessed and compared with
      radiological findings. All patients were reassessed after one year. RESULTS: The
      results in the two groups of patients show no significant difference between ERPP
      and STARR: the improvement in symptoms is similar but significant and well
      definite in both groups with a low incidence of postoperative complications.
      STARR procedure is just faster to perform even if more expensive. Dyspareunia
      slightly improved mainly in ERPP group, due probably to scar distention.
      CONCLUSION: The results of our experience indicate a significant improvement of
      symptoms with both techniques. The overall incidence rate of postoperative
      complications is low and similar between the two groups. As economical
      consideration, ERPP is less expensive.

PMID- 24901841
TI  - Hospice palliative care volunteers: the benefits for patients, family caregivers,
      and the volunteers.
AB  - OBJECTIVE: Terminally ill patients and family caregivers can benefit greatly from
      the support and care provided by trained hospice palliative care volunteers. The
      benefits of doing this kind of volunteer work also extend to the volunteers
      themselves, who often say they receive more than they give from the
      patients/families they are "privileged" to be with. The purpose of this article
      is to demonstrate how hospice palliative care volunteerism benefits both the
      patients and families who utilize this service as well as the volunteers. METHOD:
      A review of studies demonstrating how terminally ill patients, and especially
      family caregivers, can benefit from the use of hospice palliative care volunteers
      and how the volunteers themselves benefit from their experiences. RESULTS:
      Terminally ill patients and families receive many benefits from using the
      services of hospice palliative care volunteers, including emotional support,
      companionship, and practical assistance (e.g., respite or breaks from
      caregiving). Volunteering in hospice palliative care also provides many benefits
      for the volunteers, including being able to make a difference in the lives of
      others, personal growth, and greater appreciation of what is really important in
      life. SIGNIFICANCE OF RESULTS: More needs to be done to promote the value of
      hospice palliative care volunteers to those who can really benefit from their
      support and care (i.e., patients and their families) as well as to help people
      recognize the potential rewards of being a hospice palliative care volunteer. It
      is a win-win situation.

PMID- 24901840
TI  - Sequence variations of full-length hepatitis B virus genomes in Chinese patients
      with HBsAg-negative hepatitis B infection.
AB  - BACKGROUND: The underlying mechanism of HBsAg-negative hepatitis B virus (HBV)
      infection is notoriously difficult to elucidate because of the extremely low DNA
      levels which define the condition. We used a highly efficient amplification
      method to overcome this obstacle and achieved our aim which was to identify
      specific mutations or sequence variations associated with this entity. METHODS: A
      total of 185 sera and 60 liver biopsies from HBsAg-negative, HBV DNA-positive
      subjects or known chronic hepatitis B (CHB) subjects with HBsAg seroclearance
      were amplified by rolling circle amplification followed by full-length HBV genome
      sequencing. Eleven HBsAg-positive CHB subjects were included as controls. The
      effects of pivotal mutations identified on regulatory regions on promoter
      activities were analyzed. RESULTS: 22 and 11 full-length HBV genomes were
      amplified from HBsAg-negative and control subjects respectively. HBV genotype C
      was the dominant strain. A higher mutation frequency was observed in HBsAg
      negative subjects than controls, irrespective of genotype. The nucleotide
      diversity over the entire HBV genome was significantly higher in HBsAg-negative
      subjects compared with controls (p = 0.008) and compared with 49 reference
      sequences from CHB patients (p = 0.025). In addition, HBsAg-negative subjects had
      significantly higher amino acid substitutions in the four viral genes than
      controls (all p<0.001). Many mutations were uniquely found in HBsAg-negative
      subjects, including deletions in promoter regions (13.6%), abolishment of pre
      S2/S start codon (18.2%), disruption of pre-S2/S mRNA splicing site (4.5%),
      nucleotide duplications (9.1%), and missense mutations in "alpha" determinant
      region, contributing to defects in HBsAg production. CONCLUSIONS: These data
      suggest an accumulation of multiple mutations constraining viral transcriptional
      activities contribute to HBsAg-negativity in HBV infection.

PMID- 24901843
TI  - Stepping on obstacles with a sensory substitution device on the lower leg:
      practice without vision is more beneficial than practice with vision.
AB  - Practice is essential for an adapted use of sensory substitution devices.
      Understanding the learning process is therefore a fundamental issue in this field
      of research. This study presents a novel sensory substitution device worn on the
      lower leg and uses the device to study learning. The device includes 32
      vibrotactile actuators that each vibrate as a function of the distance to the
      nearest surface in a particular direction. Participants wearing the device were
      asked to approach an object and to step on the object. Two 144-trial practice
      conditions were compared in a pretest-practice-posttest design. Participants in
      the first condition practiced with vibrotactile stimulation while blindfolded.
      Participants in the second condition practiced with vibrotactile stimulation
      along with normal vision. Performance was relatively successful, both types of
      practice led to improvements in performance, and practice without vision led to a
      larger reduction in the number of errors than practice with vision. These results
      indicate that distance-based sensory substitution is promising in addition to the
      more traditional light-intensity-based sensory substitution and that providing
      appropriate sensorimotor couplings is more important than applying the
      stimulation to highly sensitive body parts. The observed advantage of practice
      without vision over practice with vision is interpreted in terms of the guidance
      hypothesis of feedback and learning. 

PMID- 24901842
TI  - Body fat percentage is a major determinant of total bilirubin independently of
      UGT1A1*28 polymorphism in young obese.
AB  - OBJECTIVES: Bilirubin has potential antioxidant and anti-inflammatory properties.
      The UGT1A1*28 polymorphism (TA repeats in the promoter region) is a major
      determinant of bilirubin levels and recent evidence suggests that raised
      adiposity may also be a contributing factor. We aimed to study the interaction
      between UGT1A1 polymorphism, hematological and anthropometric variables with
      total bilirubin levels in young individuals. METHODS: 350 obese (mean age of 11.6
      years; 52% females) and 79 controls (mean age of 10.5 years; 59% females) were
      included. Total bilirubin and C-reactive protein (CRP) plasma levels, hemogram,
      anthropometric data and UGT1A1 polymorphism were determined. In a subgroup of 74
      obese and 40 controls body composition was analyzed by dual-energy X-ray
      absorptiometry. RESULTS: The UGT1A1 genotype frequencies were 49.9%, 42.7% and
      7.5% for 6/6, 6/7 and 7/7 genotypes, respectively. Patients with 7/7 genotype
      presented the highest total bilirubin levels, followed by 6/7 and 6/6 genotypes.
      Compared to controls, obese patients presented higher erythrocyte count,
      hematocrit, hemoglobin and CRP levels, but no differences in bilirubin or in
      UGT1A1 genotype distribution. Body fat percentage was inversely correlated with
      bilirubin in obese patients but not in controls. This inverse association was
      observed either in 6/7 or 6/6 genotype obese patients. UGT1A1 polymorphism and
      body fat percentage were the main factors affecting bilirubin levels within obese
      patients (linear regression analysis). CONCLUSION: In obese children and
      adolescents, body fat composition and UGT1A1 polymorphism are independent
      determinants of total bilirubin levels. Obese individuals with 6/6 UGT1A1
      genotype and higher body fat mass may benefit from a closer clinical follow-up.

PMID- 24901844
TI  - Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.
AB  - Tear secretion is important as it supplies water to the ocular surface and keeps
      eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear
      secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal
      glands is a crucial event for tear secretion in both the pathways, the Ca2+
      channel, which is responsible for the Ca2+ elevation in the sympathetic pathway,
      has not been sufficiently analyzed. In this study, we examined tear secretion in
      mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3
      (Itpr2-/-;Itpr3-/-double-knockout mice). We found that tear secretion in both the
      parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice.
      Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and
      epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently,
      Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal
      epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal
      glands and elevation of serum autoantibodies, a representative marker for
      Sjogren's syndrome (SS) in humans, were also detected in older Itpr2-/-;Itpr3-/-
      mice. These results suggested that IP3Rs are essential for tear secretion in both
      parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be
      a new dry eye mouse model with symptoms that mimic those of SS. 

PMID- 24901845
TI  - Quantifying the association between bovine and human trypanosomiasis in newly
      affected sleeping sickness areas of Uganda.
AB  - BACKGROUND: Uganda has active foci of both chronic and acute HAT with the acute
      zoonotic form of disease classically considered to be restricted to southeast
      Uganda, while the focus of the chronic form of HAT was confined to the northwest
      of the country. Acute HAT has however been migrating from its traditional disease
      focus, spreading rapidly to new districts, a spread linked to movement of
      infected cattle following restocking. Cattle act as long-term reservoirs of human
      infective T. b. rhodesiense showing few signs of morbidity, yet posing a
      significant risk to human health. It is important to understand the relationship
      between infected cattle and infected individuals so that an appropriate response
      can be made to the risk posed to the community from animals infected with human
      pathogens in a village setting. METHODOLOGY/PRINCIPAL FINDINGS: This paper
      examines the relationship between human T. b. rhodesiense infection and human
      infective and non-human T. brucei s.l. circulating in cattle at village level in
      Kaberamaido and Dokolo Districts, Uganda. The study was undertaken in villages
      that had reported a case of sleeping sickness in the six months prior to sample
      collection and those villages that had never reported a case of sleeping
      sickness. CONCLUSIONS AND SIGNIFICANCE: The sleeping sickness status of the
      villages had a significant effect with higher odds of infection in cattle from
      case than from non-case villages for T. brucei s.l. (OR: 2.94, 95%CI: 1.38-6.24).
      Cattle age had a significant effect (p<0.001) on the likelihood of T. brucei s.l.
      infection within cattle: cattle between 18-36 months (OR: 3.51, 95%CI: 1.63-7.51)
      and cattle over 36 months (OR: 4.20, 95%CI: 2.08-8.67) had significantly higher
      odds of T. brucei s. l. infection than cattle under 18 months of age.
      Furthermore, village human sleeping sickness status had a significant effect
      (p<0.05) on the detection of T. b. rhodesiense in the village cattle herd, with
      significantly higher likelihood of T. b. rhodesiense in the village cattle of
      case villages (OR: 25, 95%CI: 1.2-520.71). Overall a higher than average T.
      brucei s.l. prevalence (>16.3%) in a village herd over was associated with
      significantly higher likelihood of T. b. rhodesiense being detected in a herd
      (OR: 25, 95%CI: 1.2-520.71).

PMID- 24901847
TI  - Growth of boronic acid based two-dimensional covalent networks on a metal surface
      under ultrahigh vacuum.
AB  - The formation of atomically precise covalent networks directly on a surface is a
      promising approach to produce single layers of two-dimensional organic materials
      (2D polymers). In the emerging field of on-surface synthesis, there is an urgent
      need for finding a rationale to new reaction pathways taking place directly on
      the surface. In this feature article we review and put into perspective recent
      results on the surface polymerisation of boronic acid based systems under
      ultrahigh vacuum conditions studied by scanning tunnelling microscopy. By
      presenting several approaches to control the growth of covalent networks, we aim
      at providing a comprehensive overview of the complex mechanisms involved. 

PMID- 24901846
TI  - Interactions between Bacillus anthracis and plants may promote anthrax
      transmission.
AB  - Environmental reservoirs are essential in the maintenance and transmission of
      anthrax but are poorly characterized. The anthrax agent, Bacillus anthracis was
      long considered an obligate pathogen that is dormant and passively transmitted in
      the environment. However, a growing number of laboratory studies indicate that,
      like some of its close relatives, B. anthracis has some activity outside of its
      vertebrate hosts. Here we show in the field that B. anthracis has significant
      interactions with a grass that could promote anthrax spore transmission to
      grazing hosts. Using a local, virulent strain of B. anthracis, we performed a
      field experiment in an enclosure within a grassland savanna. We found that B.
      anthracis increased the rate of establishment of a native grass (Enneapogon
      desvauxii) by 50% and that grass seeds exposed to blood reached heights that were
      45% taller than controls. Further we detected significant effects of E.
      desvauxii, B. anthracis, and their interaction on soil bacterial taxa richness
      and community composition. We did not find any evidence for multiplication or
      increased longevity of B. anthracis in bulk soil associated with grass compared
      to controls. Instead interactions between B. anthracis and plants may result in
      increased host grazing and subsequently increased transmission to hosts. 

PMID- 24901848
TI  - Circulating tumor cells (CTCs) detected by RT-PCR and its prognostic role in
      gastric cancer: a meta-analysis of published literature.
AB  - OBJECTIVE: The prognostic significance of circulating tumor cells (CTCs) is
      controversial in gastric cancer (GC). We performed a meta-analysis of available
      studies to assess its prognostic value detected by RT-PCR for patients diagnosed
      with GC. METHODS: EMBase, PubMed, Ovid, Web of Science, Cochrane library and
      Google Scholar database search was conducted on all studies reporting the
      outcomes of interest. The studies were set up according to the
      inclusion/exclusion criteria. Meta-analysis was performed by using a random
      effects model; hazard ratio (HR), risk ratio (RR) and their 95% confidence
      intervals (95% CIs) were set as effect measures. The information about trial
      design, results from the data was independently extracted. Heterogeneity of the
      studies was tested for each pooled analysis. RESULTS: Nineteen studies published
      matched the selection criteria and were included in this meta-analysis. CTCs
      positivity was significantly associated with poor relapse free survival (RFS) (HR
      2.42, 95% CI: [1.94-3.02]; P<0.001) and poor overall survival (OS) (HR 2.42, 95%
      CI: [1.94-3.02]; P<0.001). CTCs positivity were also significantly associated
      with regional lymph nodes (RLNs) metastasis (RR 1.42, 95% CI: [1.20-1.68];
      p<0.0001), depth of infiltration (RR 1.51, 95% CI: [1.27-1.79]; p<0.0001),
      vascular invasion (RR  = 1.43, 95% CI: [1.18-1.74], p = 0.0002) and TNM
      stage(I,II versus III) (RR 0.63, 95% CI [0.48-0.84]; p = 0.001). CONCLUSION:
      Preoperative CTCs positivity indicates poor prognosis in patients with gastric
      cancer, and associated with poor clinicopathological prognostic factors.

PMID- 24901851
TI  - Outcomes of biventricular mechanical support patients discharged to home to await
      heart transplantation.
AB  - BACKGROUND: The use of left ventricular assist devices has grown rapidly in
      recent years for patients with end-stage heart failure. A significant proportion
      of patients require both left- and right-sided support with biventricular assist
      devices (BiVADs) as a bridge to transplantation. Traditionally, these patients
      have waited in the hospital until they receive a transplant. PURPOSE: The aim of
      this study was to characterize the clinical course of BiVAD patients discharged
      to home to await heart transplantation. METHODS: Between November 2009 and July
      2011, 24 adult patients underwent Thoratec paracorporeal BiVAD placement at the
      University of California Los Angeles, all with an Interagency Registry for
      Mechanically Assisted Circulatory Support score 1 or 2. The disposition,
      complications, and rehospitalizations of these subjects were retrospectively
      reviewed. RESULTS: Fourteen of the 24 patients were successfully discharged to
      home, with a mean time of 60 +/- 27 days from BiVAD implantation to discharge.
      Ninety-three percent (13/14) of the patients sent home went on to be
      transplanted. Eleven of the 14 (79%) came in from home to receive their
      transplant. The mean time from BiVAD implantation to transplantation was 100 +/-
      65 days. Of the 14 patients discharged to home, there were 18 readmissions in 8
      patients. CONCLUSION: In this small single-center review, we found that complex
      medical patients with BiVADs can be discharged to home and can await a heart
      transplant from home under the close management of multidisciplinary acute care
      and outpatient teams.

PMID- 24901849
TI  - Both alpha2,3- and alpha2,6-linked sialic acids on O-linked glycoproteins act as
      functional receptors for porcine Sapovirus.
AB  - Sapovirus, a member of the Caliciviridae family, is an important cause of acute
      gastroenteritis in humans and pigs. Currently, the porcine sapovirus (PSaV)
      Cowden strain remains the only cultivable member of the Sapovirus genus. While
      some caliciviruses are known to utilize carbohydrate receptors for entry and
      infection, a functional receptor for sapovirus is unknown. To characterize the
      functional receptor of the Cowden strain of PSaV, we undertook a comprehensive
      series of protein-ligand biochemical assays in mock and PSaV-infected cell
      culture and/or piglet intestinal tissue sections. PSaV revealed neither
      hemagglutination activity with red blood cells from any species nor binding
      activity to synthetic histo-blood group antigens, indicating that PSaV does not
      use histo-blood group antigens as receptors. Attachment and infection of PSaV
      were markedly blocked by sialic acid and Vibrio cholerae neuraminidase (NA),
      suggesting a role for alpha2,3-linked, alpha2,6-linked or alpha2,8-linked sialic
      acid in virus attachment. However, viral attachment and infection were only
      partially inhibited by treatment of cells with sialidase S (SS) or Maackia
      amurensis lectin (MAL), both specific for alpha2,3-linked sialic acid, or
      Sambucus nigra lectin (SNL), specific for alpha2,6-linked sialic acid. These
      results indicated that PSaV recognizes both alpha2,3- and alpha2,6-linked sialic
      acids for viral attachment and infection. Treatment of cells with proteases or
      with benzyl 4-O-beta-D-galactopyranosyl-beta-D-glucopyranoside (benzylGalNAc),
      which inhibits O-linked glycosylation, also reduced virus binding and infection,
      whereas inhibition of glycolipd synthesis or N-linked glycosylation had no such
      effect on virus binding or infection. These data suggest PSaV binds to cellular
      receptors that consist of alpha2,3- and alpha2,6-linked sialic acids on
      glycoproteins attached via O-linked glycosylation. 

PMID- 24901850
TI  - The distribution and common amino acid polymorphisms of human papillomavirus
      (HPV)-31 variants in 2700 women from Northern China.
AB  - To investigate the distribution of Human papillomavirus (HPV)-31 A, B and C
      variants as well as the common amino acid polymorphisms in Chinese women, all 14
      HPV-31 positive cervical exfoliated cell specimens identified from a descriptive
      study including ~2700 women from Northern China were analyzed. HPV-31 positive
      specimens were identified by Mass Spectrometry and the fragments of partial Long
      Control Region, E6 and E7 were amplified and directly sequenced or cloned into
      vector and then sequenced to confirm the variant information. HPV-31 prevalence
      in Northern Chinese female population was 0.52%. Six different sequences
      represented all 14 isolates, and these isolates were subsequently classified into
      variant lineage A (9), B (0) and C (5) by phylogenetic analysis. Five common
      amino acid polymorphism sites (2 in E6 and 3 in E7) and a novel non-synonymous
      mutation were detected in the current study. Our investigation suggested that HPV
      31 was much less detected in Chinese women population than that in western
      countries. A and C variants were commonly detected while B variants were rarely
      detected in this population. 

PMID- 24901852
TI  - Human autologous serum as a substitute for fetal bovine serum in human Schwann
      cell culture.
AB  - Nowadays, cell -based and tissue engineered products have opened new horizons in
      treatment of incurable nervous system disorders. The number of studies on the
      role of Schwann cells (SC) in treating nervous disorders is higher than other
      cell types. Different protocols have been suggested for isolation and expansion
      of SC which most of them have used multiple growth factors, mitogens and fetal
      bovine sera (FBS) in culture medium. Because of potential hazards of animal
      derived reagents, this study was designed to evaluate the effect of replacing FBS
      with human autologous serum (HAS) on SC's yield and culture parameters. Samples
      from 10 peripheral nerve biopsies were retrieved and processed under aseptic
      condition. The isolated cells cultured in FBS (1st group) or autologous serum
      (2nd group). After primary culture the cells were seeded at 10000 cell/cm2 in a
      12 wells cell culture plate for each group. At 100% confluency, the cell culture
      parameters (count, viability, purity and culture duration) of 2 groups were
      compared using paired t-test. The average donors' age was 35.80 (SD=13.35) and
      except for 1 sample the others cultured successfully. In first group, the
      averages of cell purity, viability and culture duration were 97% (SD=1.32),
      97/33% (SD=1.22) and 11.77 (SD=2.58) days respectively. This parameters were
      97.33% (SD=1.00), 97.55% (SD=1.33) and 10.33 days (SD=1.65) in second group. The
      difference of cell count, purity and viability were not significant between 2
      groups (P>0.05). The cells of second group reached to 100% confluency in shorter
      period of time (P=0.03). The results of this study showed that autologous serum
      can be a good substitute for FBS in human SC culture. This can reduce the costs
      and improve the safety of cell product for clinical application. 

PMID- 24901854
TI  - Prevalence of G6PD deficiency in Iran, a mata-analysis.
AB  - Search results show that numerous primary studies have been carried out in
      different parts of Iran regarding prevalence of G6PD deficiency; if results of
      these studies are combined, a reliable estimation of prevalence of this factor
      will be achieved in Iran. Thus, present study, aimed to determine the prevalence
      of G6PD deficiency by combining findings of qualified primary studies using meta
      analysis and taking into account heterogeneity considerations. Searching the
      relevant keywords in Iranian and International databases, primary studies were
      selected. After quality appraisal and applying inclusion and exclusion criteria,
      relevant primary studies were selected. In each study, standard error of
      prevalence of G6PD was calculated according to binominal distribution formula.
      Finally, heterogeneity index was determined among studies using Cochran's test.
      Prevalence of G6PD in Iran was estimated by STATA software ver 11 using fixed or
      random effect model based on heterogeneity results. 148916 subjects in 36 primary
      studies which entered this meta-analysis were examined. G6PD deficiency
      prevalence was 6.7% in Iran (men: 8.8% and women: 2.2%). Also, this deficiency in
      the present study was four times higher in men than in women. Its prevalence was
      adjusted in different parts of Iran and it was shown that it was between 0.8 and
      15.2 using Bayesian analysis. This meta-analysis showed that Iran is among
      countries with high frequency of G6PD deficiency and there is a significant
      difference in prevalence of G6PD in different parts of Iran. According to these
      results, screening newborn children seems very vital. Carrying out other primary
      studies regarding prevalence of G6PD seems unnecessary. 

PMID- 24901853
TI  - Cyclic AMP pathway modifies memory through neural cell adhesion molecule
      alterations in the rat hippocampus.
AB  - Neural Cell Adhesion Molecules (NCAMs) are known to influence memory by affecting
      neural cell-cell and cell-extracellular matrix junctions. This study investigated
      the possible role of cAMP pathway in the expression of hippocampal NCAM and its
      polysialylated derivative (PSA-NCAM). The following pharmacological tools were
      employed for manipulation of cAMP pathway: a) forskolin; the activator of
      adenylyl cyclase (AC), b) 8-Br-cAMP; a protein kinase A (PKA) agonist, c) 8-pCPT
      2'-O-Me-cAMP; a selective enhancer of exchange protein activated by cAMP (Epac)
      and d) Rp-cAMP; a PKA inhibitor. Memory acquisition was tested by passive
      avoidance paradigm after injecting the above compounds for three consecutive days
      into the CA1 region of dorsal hippocampus of rats. Forskolin and 8-Br-cAMP
      enhanced memory retrieval while Rp-cAMP significantly reduced memory and NCAM
      levels. 8-pCPT-2'-O-Me-cAMP failed to alter memory performance or NCAM levels as
      compared to vehicle. We observed no significant changes in PSA-NCAM, however the
      expression of St8sia4 and St8sia2 (the polysialyltransferase isoforms) were
      altered. The mRNA levels of St8sia4 was down-regulated by 8-Br-cAMP, Rp-cAMP and
      8-pCPT while forskolin led to almost 3 and 5 fold increase in mRNAs of St8sia2
      and St8sia4, respectively. The current insight might endorse the predominant role
      of PKA as compared to Epac in cAMP pathway in expression of NCAM and memory
      function. 

PMID- 24901855
TI  - Osteoprotegerin and soluble receptor activator of nuclear factor-kappa B ligand
      in exudative age-related macular degeneration.
AB  - Calcification and inflammation are among the important cases of exudative age
      related macular degeneration (E-ARMD). The aim of the present study was to
      elucidate if there is any relationship between serum Osteoprotegerin (OPG),
      soluble receptor activator of nuclear factor-kappa B ligand (RANK-ligand) and E
      ARMD. In a cross-sectional study, we compared 45 E-ARMD patients with 45 matched
      controls. Diagnosis was confirmed by fluorescein angiography. Serum samples were
      analyzed for OPG, RANK-ligand, low density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride
      (TG). The levels of OPG and RANK-ligand were measured by ELISA methods. The mean
      age was 72.0+/-11.5 years in the E-ARMD group and 68.2+/-8.9 years in the control
      group (p=0.09). The level of serum OPG was 132.10+/-75.49 pg/ml in the E-ARMD
      group and 94.88+/-61.65 pg/ml in the control subjects. E-ARMD patients had
      significantly high levels of OPG (p=0.012), as well as significantly high levels
      of LDL-C and TC (p=0.001 and p=0.005, respectively). We could not find any
      significant difference in RANK-ligand, HDL-C, or TG between two study groups
      (p>0.05). To the best of our knowledge, this is the first study investigating the
      levels of OPG in E-ARMD patients. The present study showed that E-ARMD patients
      had high levels of serum OPG. It may act as a protective factor for E-ARMD or
      only as a secondary phenomenon of different processes of E-ARMD. Further
      prospective studies would be necessary for prognostic and predictive significance
      of OPG in patients affected by E-ARMD. 

PMID- 24901856
TI  - Helicobacter pylori eradication in renal recipient: triple or quadruple therapy?
AB  - Although triple (omeprazole, amoxicillin, and metronidazole) and quadruple
      (omeprazole, tetracycline, metronidazole, and bismuth subcitrate) therapeutic
      regimens for H. pylori eradication has been studied much in the general
      population, there is a lack of data in renal transplanted patients. So, this
      study aimed at comparing regimens in these patients who were considered being
      immunocompromised. The present clinical trial was carried out in Mashhad, Iran in
      2010. Fifty-five patients who had received a kidney transplant in six months or
      earlier and referred for chronic dyspepsia were selected. They were resistant to
      H2-receptor antagonists or proton pump inhibitors therapy and had positive Rapid
      Urea Test. They randomly divided into two groups: triple and quadruple therapy.
      The treatment duration in both groups was similar (antibiotics for two weeks plus
      omeprazole for 4 weeks). Urea Breath Test (UBT) was performed two weeks after
      treatment for assessment of its result. Total numbers of 39 patients (71%) were
      positive for H. Pylori which were divided into triple therapy group (21 patients)
      and quadruple therapy (18 patients). Overall, the treatment was successful in 80%
      (71% in triple therapy and 89% in quadruple one) which was not different
      significantly between the groups (p=0.247). The result of this study revealed
      that the prevalence of H. pylori infection in renal transplant patients is
      similar to the normal population. In these cases, triple and quadruple therapies
      were similar in eradication of H. pylori. So, triple therapy can be recommended
      in renal transplant recipients.

PMID- 24901857
TI  - Erythropoietin plus methylprednisolone or methylprednisolone in the treatment of
      acute spinal cord injury: a preliminary report.
AB  - Recent studies in animal models indicate that recombinant human erythropoietin
      (rhEPO) is very effective in enhancing neurological recovery after spinal cord
      injury (SCI). We aimed to evaluate the effect of rhEPO plus methylprednisolone
      sodium succinate (MPSS) compared to MPSS alone to improve neurological function
      of patients after SCI in a randomized clinical trial. During a 15-month period 30
      patients presenting to emergency departments of two university affiliated
      hospitals within less than 6 hours after acute SCI were randomized to two groups.
      Both groups received MPSS 30 mg/kg initially and 5.4 mg/kg every hour till 23
      hours if admitted within 3 hours and till 47 hours if recruited within 3-6 hours
      after injury. Group EPO also received 500 unit/kg rhEPO on admission and another
      500 unit/kg 24 hours later instead of placebo in group MPSS. Neurologic
      evaluation was performed on admission, 24, 48, 72 hours and one and 6 months
      later. Range of patients' age was 18-65 years. There was no significant
      difference between patients receiving two types of treatment in neurological exam
      on admission (P=0.125), 24 hours after admission (P=0.108) and 48 hours after
      admission (P=0.085). However, one week (P=0.046), one month (P=0.021) and six
      months (P=0.018) after admission these differences were significant. MPSS plus
      rhEPO started within 6 hours after acute spinal injury may be more effective than
      MPSS plus placebo in improvement of neurologic dysfunction. More studies with
      larger sample sizes are warranted.

PMID- 24901858
TI  - The effects of maternal passive smoking on maternal milk lipid.
AB  - Passive smoking was long overlooked by those in the medical and legal professions
      as being harmful to one's health, but in recent years the negative effect of
      passive smoking has come to the fore in the media and laws have been changed so
      that less people are obliged to unwillingly suffer from passive smoking,
      particularly in the workplace and in indoor settings. To study the effects of
      environmental tobacco smoking exposure during the breast-feeding period on
      maternal milk lipids. This cohort study was conducted on 45 mothers environmental
      tobacco smoking exposure and 40 non-exposed post-partum mothers referred to the
      Shahid Ayat health center, Tehran, Iran. Socioeconomic conditions and the
      demographic characteristics of exposed and non-exposed groups were recorded. Milk
      samples were collected twice--at baseline (5-7 days after delivery) and four
      months after delivery. The samples were reserved at -20 degrees C until assay.
      Milk lipids including cholesterol, triglyceride (TG), high density lipoprotein
      (HDL) and low density lipoprotein (LDL) were evaluated. Dietary intake assessment
      was performed by means of the 24-hour dietary recall questionnaire both times.
      Maternal occupation status and education levels were significantly different
      between the two groups. Lipids profiles of milk were significantly higher 5-7
      days after delivery in the non-exposed group and four months after delivery.
      Dietary intake was not significantly different between the two groups. Maternal
      environmental tobacco smoking exposure affects milk lipids which are essential
      for infant growth.

PMID- 24901859
TI  - Systemic EBV T-cell lymphoproliferative disease of young adults.
AB  - T/NK cell proliferative EBV associated disease is a rare one which is more common
      in eastern Asian countries. EBV is originally associated with B cells, and EBV
      associated T cell lymphoma is so rare. Hence we decided to describe a patient
      treated with misleading diagnoses such as TB and sarcoidosis for almost two
      years. The liver was biopsied after admission in this center, and gastric and
      colonic biopsy was also performed due to gastrointestinal bleeding. Diffuse
      infiltration of chronic inflammatory cells was seen, especially lymphocytes some
      of which were atypical. T lymphocyte markers were seen in these cells by
      immunohistochemical staining. Further studies demonstrated T lymphocytes
      associated with EBV to be positive which is very rare event. Although going under
      chemotherapy, there were no response and the patient died. 

PMID- 24901860
TI  - The relation between serum vitamin D levels and blood pressure: a population
      based study.
AB  - Vitamin D deficiency has been proposed as an associating factor with increased
      blood pressure. We studied the relationship between serum vitamin D and blood
      pressure in a large representative sample of Iranian population. In this cross
      sectional study, based on the data of 2508 adults (aged between 20 and 70 years)
      from the Iran Multicenter Osteoporosis Study (IMOS), the association between
      serum vitamin D and blood pressure was investigated. There was a significant
      difference between mean (+/-SD) vitamin D levels of the individuals with stage I
      hypertension and that of the three other groups (Normal: 32.9 (+/-27.5);
      Prehypertension: 34.4 (+/-27.2); Stage-I: 38.7 (+/-29.2); Stage-II: 34.7 (+/
      24.0) ng/ml; P<0.05. In multivariate regression models, the weak positive
      association of vitamin D and systolic blood pressure values disappeared after age
      and Body Mass Index (BMI) adjustment. We found a statistically positive but weak
      association between vitamin D serum concentration and systolic blood pressure.
      Considering the difference noted between our results and previous studies,
      further research is needed to assess the potential effect of ethnicity and
      genetic factors on these findings. 

PMID- 24901861
TI  - Prevalence of behavioral inhibition among preschool aged children in Tehran,
      Iran.
AB  - One of the identified risk factors for anxiety disorders in adolescence and
      adulthood is inhibited behaviors in childhood. The present study sought to
      examine the relationship between behavioral inhibition with some of the internal
      (personal) and external (family environment) factors in a sample of preschool
      children in kindergartens. In a cross sectional study in 2009, data was collected
      trough a structured questionnaire completed by parents and teachers in day-care
      centers. A total of 1403 children were assessed. Analysis was performed through
      complex sample analysis. The results showed that 7.4% (CI95%= 6.1%-9.1%) of
      children according to parents' and 8.1% (CI95%= 6%- 10.7%) according to teachers'
      evaluation classified as behaviorally inhibited. The higher levels of behavioral
      inhibition were shown by girls, first children, single parent families and older
      children. Birth year before 2004, birth rank, living in a single parent family
      and maternal level of education were independent predictors for behavioral
      inhibition in logistic regression modeling. There is relatively high prevalence
      of inhibited behaviors among Iranian children. Further examination of diagnosed
      children with behavioral inhibition by experienced psychiatrists is needed. Also
      establishing consultation centers for behaviorally inhibited children and
      instructing their parents and teachers are recommended. 

PMID- 24901863
TI  - Outbreak of serial knee joint sepsis after arthroscopic surgery: a case series
      with the guideline for treatment.
AB  - Knee infection after arthroscopic surgeries is rare but devastating complication.
      A serial knee joint infection occurred in our hospital after the contamination of
      arthroscopic equipments set with an unknown microorganism. Herein we describe the
      natural course of these patients and suggest a treatment protocol according to
      the experiment gained from management of these patients. 

PMID- 24901862
TI  - The assessment of affected factors on cytomegalovirus and rubella virus
      prevalence in females in Hamadan, Iran.
AB  - Cytomegalovirus (CMV) and rubella are considered as dangerous viral infections to
      the fetus. The findings of this research can clear the possible progress made
      thus far toward prevention in this part of the country. The data of all referees
      to genetic center of Shahid Beheshti Hospital in Hamadan, including the rubella
      and CMV tests were recorded in questionnaires and analyzed by logistic regression
      models. Univariate and multivariate logistic regression were utilized to assess
      the affected factors on CMV and Rubella separately. STATA and SPSS16 statistical
      software were used with setting P-value as 0.05. Logistic regression analysis
      indicates a statistically significant relationship between CMV IgM and on
      occupation (P=0.045), pregnancy (P=0.03) and years of referring the patients
      (P<0.001). The results of multivariate logistic regression analysis showed that
      job was significantly affected on the CMV infection [OR (95% C.I) = 1.71(1.1
      2.83)]. Univariate logistic regression showed that age (P=0.001), the residential
      area (P=0.03), pregnancy (P=0.03), the marital status (P=0.022) and years of
      referring the patients (P<0.0001) has a significant effect on rubella IgG.
      However, multivariate logistic regression analysis also showed that residential
      status (OR=1.77) and age (OR=0.63) were significantly affected on the Rubella
      infection. The high level of IgG positivity against rubella in females may
      highlight the considerable impact of increasing public vaccination in this part
      of Iran. Also, the current data demonstrating frequency of primary infections
      with CMV in females which support the conclusion that regular prenatal screening
      tests is justified. 

PMID- 24901864
TI  - Sexual function in women with multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory disease of central nervous system
      (CNS) and sexual dysfunction (SD) is one of the most common disabilities of MS
      women. The aim of this study was to determine sexual function of women with MS
      (multiple sclerosis). One hundred definite MS patients MS patients and fifty age
      matched healthy controls were enrolled. Demographic data (sex, age), duration of
      the disease and disease pattern extracted from patient's  files and Kurtzke
      Expanded Disability Status Scale (EDSS) recorded for each patient by an expert
      neurologist. Participants were asked to answer the valid and reliable Persian
      version of Beck depression inventory (BDI) and Female Sexual Function Index
      (FSFI) questionnaires. The total FSFI score and subscale scores differed
      significantly between the MS patients and the controls. There was a significant
      negative correlation between EDSS and FSFI scores (rho=-0.44, P<0.001) and
      significant positive correlation between EDSS and BDI (rho=0.36, P<0.001) in
      patients. Mean BDI and all subscales of FSFI differed significantly between
      patients with total FSFI score higher and lower than 26.55. Sexual dysfunction
      should be considered in women with multiple sclerosis. 

PMID- 24901865
TI  - An unusual presentation of ossified intramuscular hemangioma: a case report.
AB  - Intramuscular cavernous hemangiomas represent less than 1% of all hemangiomas.
      Typical presentation is a soft-tissue mass and/or pain without cutaneous changes.
      Whereas calcification of hemangiomas is common; ossification of these lesions is
      very rare. We describe a case of ossified intramuscular hemangioma of quadriceps
      presented with painless knee extension contracture and thigh mass. 

PMID- 24901866
TI  - A neonate with indurate dermal papules and nodules and pneumonia: a case report.
AB  - We presents an infant with several indurated plaques and nodules scattered on her
      body. She was brought to the hospital because of fever, runny nose and cough from
      one month ago. During the examination and investigation the plaques and nodules
      grabbed the attention of the clinicians and the skin biopsy and other lab works
      revealed the diagnosis of congenital leukemia. 

PMID- 24901867
TI  - Sudden impolite behavior in a polite girl: a case report.
AB  - In this case we present a previously healthy child with sudden behavioral change
      and acute confusional state (ACS). ACS is a neurologic emergency. The clinical
      manifestations of ACS are; confused affect, limited verbal response, disturbance
      in performing orders, some automatism, stable vital signs and absence of tonic
      clonic movements and it has a wide range of differential diagnosis which should
      be assessed by detailed medical history, medical examination and laboratory
      tests. The only abnormal test found in this patient, was cerebrospinal fluid
      abnormality, consistent with viral encephalitis. 

PMID- 24901868
TI  - Attitude toward plagiarism.

PMID- 24901870
TI  - Mode switching of a self-propelled camphor disk sensitive to the
      photoisomerization of a molecular layer on water.
AB  - A simple self-propelled motor on a 4-[[(dodecyloxy)benz-4-yl]azo]benzoic acid
      (DBA) molecular layer was investigated from the viewpoint of motor control
      depending on the molecular structure. The nature of the self-motion of a camphor
      disk on the DBA molecular layer changed depending on the surface pressure (pi)
      area (A) isotherm of DBA, which in turn changed by the photoisomerization between
      UV and green lights. The characteristic motion of the camphor disk is discussed
      in relation to the pi-A isotherm of DBA, which changes depending on the
      photoisomerization as the driving force of motion. 

PMID- 24901869
TI  - Oxidative stress decreases functional airway mannose binding lectin in COPD.
AB  - We have previously established that a defect in the ability of alveolar
      macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is
      a potential therapeutic target in COPD. We further showed that levels of mannose
      binding lectin (MBL; required for effective macrophage phagocytic function) were
      reduced in the airways but not circulation of COPD patients. We hypothesized that
      increased oxidative stress in the airway could be a cause for such disturbances.
      We therefore studied the effects of oxidation on the structure of the MBL
      molecule and its functional interactions with macrophages. Oligomeric structure
      of plasma derived MBL (pdMBL) before and after oxidation (oxMBL) with 2,2'
      azobis(2-methylpropionamidine)dihydrochroride (AAPH) was investigated by blue
      native PAGE. Macrophage function in the presence of pd/oxMBL was assessed by
      measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae
      (NTHi) and expression of macrophage scavenger receptors. Oxidation disrupted
      higher order MBL oligomers. This was associated with changed macrophage function
      evident by a significantly reduced capacity to phagocytose apoptotic cells and
      NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively).
      Interestingly, oxidation of MBL significantly reduced macrophage phagocytic
      ability to below control levels. Flow cytometry and immunofluorescence revealed a
      significant increase in expression of macrophage scavenger receptor (SRA1) in the
      presence of pdMBL that was abrogated in the presence of oxMBL. We show the
      pulmonary macrophage dysfunction in COPD may at least partially result from an
      oxidative stress-induced effect on MBL, and identify a further potential
      therapeutic strategy for this debilitating disease. 

PMID- 24901872
TI  - The merits of measuring challenge and hindrance appraisals.
AB  - BACKGROUND AND OBJECTIVES: The challenge-hindrance framework has shown that
      challenge stressors (work characteristics associated with potential personal
      gain) tend to have positive outcomes, whereas hindrance stressors (those which
      obstruct goals) have negative outcomes. However, typical research methods assume
      that stressors allocated to these categories are appraised consistently by
      different people and across different situations. We validate new measures of
      challenge and hindrance appraisals and demonstrate their utility in stress
      research. DESIGN AND METHODS: We used a cross-sectional survey of American
      employees (Study 1, n = 333), a diary survey of Australian employees (Study 2, n
      = 241), and a survey of Australian college students whose performance was
      evaluated independently (Study 3, n = 350). RESULTS: Even after accounting for
      the effects of stressors, challenge and hindrance appraisals consistently
      explained unique variance in affective states, with indications that stressors
      have indirect effects via appraisals. Such effects were seen within- as well as
      between-participants (Study 2). Appraisals also had expected associations with
      specific coping behaviors (Study 1), while challenge appraisal was associated
      with task performance (Study 3). CONCLUSIONS: The scales of challenge and
      hindrance appraisals were psychometrically sound across multiple contexts.
      RESULTS highlight the merit of considering appraisal in stress research.

PMID- 24901871
TI  - KIR2DS4 promotes HIV-1 pathogenesis: new evidence from analyses of immunogenetic
      data and natural killer cell function.
AB  - BACKGROUND: KIR2DS4 gene variants encode full-length and truncated protein
      products, with only the former serving as membrane-bound receptors to activate
      natural killer (NK) cells. We have previously shown that full-length KIR2DS4 was
      associated with relatively high viral load and accelerated heterosexual HIV-1
      transmission. Our objective here was to provide confirmatory data and to offer
      new insights about the potential mechanisms. METHODOLOGY/PRINCIPAL FINDINGS:
      Mixed models for repeated (longitudinal) outcome measurements on 207 HIV-1
      seropositive American youth revealed an association of full-length KIR2DS4 with
      relatively high viral load and low CD4+ T-cell count (p<0.01 for both). Depending
      on KIR2DS4 expression (presence or absence) on cell surface, NK cells from 43
      individuals with untreated, chronic HIV-1 infection often differed in functional
      properties, including degranulation and secretion of IFN-gamma and MIP-1beta. In
      particular, polyfunctional NK cells were enriched in the KIR2DS4-positive subset.
      CONCLUSIONS/SIGNIFICANCE: Full-length KIR2DS4 promotes HIV-1 pathogenesis during
      chronic infection, probably through the maintenance of an excessively pro
      inflammatory state.

PMID- 24901874
TI  - Efficacy of a Short Plate With an Oblique Screw Trajectory for Anterior Cervical
      Plating: A Comparative Study With a 2-Year Minimum Follow-Up.
AB  - STUDY DESIGN: A retrospective case-control study. BACKGROUND CONTEXT: It has been
      reported that adjacent segment ossification development (ASOD) commonly occurs
      after anterior cervical arthrodesis. OBJECTIVE: The aim of this study was to
      compare the efficacy of the short plate and oblique screw trajectory with the
      traditional long plate and parallel screw trajectory by investigating the
      incidence of ASOD and graft subsidence. MATERIALS AND METHODS: We retrospectively
      reviewed the patients who underwent single-level anterior cervical discectomy and
      fusion (ACDF) with plate augmentation in our institute between June 2003 and
      August 2011. The patients were divided into 2 groups according to the plating
      technique, which was determined by the distances between the tips of the plate
      and the cranial and caudal adjacent endplates (plate-to-endplate distance, PED).
      Group L included the patients with a long plate (PED shorter than 5 mm), and
      group S contained the patients with a short plate (PED longer than 5 mm).
      Vertebral body height, distribution of ACDF level, incidence of cranial and
      caudal ASOD, ASOD grade, screw-to-endplate angle, vertebral body diameter, screw
      length, screw-to-body ratio, disk space height, subsidence, and cervical range of
      motion were measured and compared between the 2 groups. RESULTS: The incidences
      of both cranial and caudal ASOD at least 2 years after surgery in group S were
      significantly lower than in group L (17.6% vs. 53.8%, P=0.001 and 31.4% vs.
      65.4%, P=0.004, respectively). The incidence of severe ASOD at the caudal
      adjacent disk space was significantly lower in group S (2.0% vs. 23.0%, P=0.002).
      The incidence of the subsidence was significantly lower in group S (2.0% vs.
      25.9, P=0.001). Changes in the cervical range of motion showed no significant
      differences regardless of group, ASOD, and graft subsidence. CONCLUSIONS:
      Techniques using a short plate with an oblique screw trajectory resulted in
      significantly reduced incidence and severity of ASOD and prevented graft
      subsidence.

PMID- 24901876
TI  - Unilateral versus bilateral vertebroplasty for severe osteoporotic vertebral
      compression fractures.
AB  - STUDY DESIGN: This was a prospective study of patients who underwent
      vertebroplasty (VP) at a single institute. OBJECTIVE: The aim of this study was
      to assess and compare the clinical outcomes and complications of unilateral and
      bilateral VP in treating severe vertebral compression fractures. SUMMARY OF
      BACKGROUND DATA: Typically, VP involves cement injection by bilateral
      transpedicular or extrapedicular approach. Recently, several articles reported
      that unilateral VP can achieve comparable outcomes in most cases. However, few
      prospective randomized studies compared the clinical outcomes and complications
      in treating severe vertebral compression fractures. METHODS: Thirty-nine patients
      with 44 severe osteoporotic vertebral compression fractures (OVCFs) were randomly
      allocated into 2 groups adopting unilateral or bilateral VP. Preoperative and
      postoperative pain scores, back disability, and cement leakage were recorded and
      compared. RESULTS: Significant improvement on the visual analog scale and
      Oswestry disability index scores were noted in each group, and there were no
      significant differences between the 2 groups. Cement leakage was seen more in
      bilateral VP. CONCLUSIONS: Severe OVCFs should be candidates for VP. The
      unilateral VP can get the same clinical results with fewer complications compared
      with the bilateral VP.

PMID- 24901877
TI  - The increased prevalence of cervical spondylosis in patients with adult
      thoracolumbar spinal deformity.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess the concomitance
      of cervical spondylosis and thoracolumbar spinal deformity. SUMMARY OF BACKGROUND
      DATA: Patients with degenerative cervical spine disease have higher rates of
      degeneration in the lumbar spine. In addition, degenerative cervical spine
      changes have been observed in adult patients with thoracolumbar spinal
      deformities. However, to the best of our knowledge, there have been no studies
      quantifying the association between cervical spondylosis and thoracolumbar spinal
      deformity in adult patients. METHODS: Patients seen by a spine surgeon or spine
      specialist at a single institution were assessed for cervical spondylosis and/or
      thoracolumbar spinal deformity using an administrative claims database. Spinal
      radiographic utilization and surgical intervention were used to infer severity of
      spinal disease. The relative prevalence of each spinal diagnosis was assessed in
      patients with and without the other diagnosis. RESULTS: A total of 47,560
      patients were included in this study. Cervical spondylosis occurred in 13.1%
      overall, but was found in 31.0% of patients with thoracolumbar spinal deformity
      (OR=3.27, P<0.0001). Similarly, thoracolumbar spinal deformity was found in 10.7%
      of patients overall, but was increased at 23.5% in patients with cervical
      spondylosis (OR=3.26, P<0.0001). In addition, increasing severity of disease was
      associated with an increased likelihood of the other spinal diagnosis. Patients
      with both diagnoses were more likely to undergo both cervical (OR=3.23, P<0.0001)
      and thoracolumbar (OR=4.14, P<0.0001) spine fusion. CONCLUSIONS: Patients with
      cervical spondylosis or thoracolumbar spinal deformity had significantly higher
      rates of the other spinal diagnosis. This correlation was increased with
      increased severity of disease. Patients with both diagnoses were significantly
      more likely to have received a spine fusion. Further research is warranted to
      establish the cause of this correlation. Clinicians should use this information
      to both screen and counsel patients who present for cervical spondylosis or
      thoracolumbar spinal deformity.

PMID- 24901878
TI  - Long-term Treatment Effects of Lumbar Arthrodeses in Degenerative Disk Disease: A
      Systematic Review With Meta-Analysis.
AB  - STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVE: To (1) evaluate
      long-term patient-centered clinical outcomes after lumbar arthrodesis with or
      without decompression for lumbar spondylosis (LS); and (2) compare these outcomes
      with those of alternative treatments, including nonsurgical and surgical which
      maintain mobility of the lumbar spine. SUMMARY OF BACKGROUND DATA: The effective
      treatment of LS is a complex clinical and economic concern for patients and
      health care providers. METHODS:  SELECTION CRITERIA: (1) randomized controlled
      clinical trials (RCTs) comparing treatment effects of lumbar arthrodesis with
      other interventions; (2) participants: skeletally mature adults with lumbar
      degenerative disk disease. SEARCH METHODS: Ovid MEDLINE, Embase, the Cochrane
      Library, and others. All years through February of 2013 were included. Patient
      centered clinical outcomes before treatment, at 12, 24, or >24 months of follow
      up, and rate of complications and additional surgical treatment were collected. A
      meta-analysis was performed to evaluate pooled treatment effects. The GRADE
      approach was applied to evaluate the level of evidence. RESULTS: The review
      included 38 studies of 5738 participants. All studies showed strong or at least
      moderate treatment effects of lumbar arthrodesis at 12, 24, and 48-72 months of
      follow-up. The level of evidence was moderate at 12 and 24 months, and low at 48
      72 months. The pooled long-term treatment effect of lumbar arthrodesis exceeded
      those of: nonsurgical treatment (P<0.0001) with a moderate level of evidence, and
      decompression without fusion (P=0.005) with a low level of evidence. The
      treatment effect of lumbar arthrodesis showed a small inferiority versus
      arthroplasty at 12 and 24 months of follow-up (P<0.001), but not after 24 months
      postoperative. CONCLUSIONS: This review indicates that surgical stabilization of
      the lumbar spine is an effective treatment for LS; in particular, for patients
      with severe chronic low back pain that has been resistant to >=3 months of
      conservative therapy.

PMID- 24901879
TI  - Acute cervical myelopathy due to presumed fibrocartilaginous embolism: a case
      report and systematic review of the literature.
AB  - INTRODUCTION: Fibrocartilaginous embolism (FCE) is an uncommon cause of
      myelopathy that should be considered after more common causes have been ruled
      out. OBJECTIVE: This article presents a case report of a 50-year-old man with
      acute myelopathy attributed to FCE and summarizes the clinical features of the
      disease by analyzing all of the published evidence. DATA SOURCES AND EXTRACTION:
      Two computerized literature searches (MEDLINE-Pubmed, EMBASE, the Cochrane
      Library) were performed. The search term used was "Fibrocartilaginous embolism."
      No language restrictions were applied. All articles were evaluated and key data
      were extracted according to predefined criteria: patient's age, year of
      publication, localization of the embolism and type of vascular syndrome, clinical
      outcome, and time to death in the fatal cases. RESULTS: Fifty-two cases (39
      biopsy proven and 13 clinically diagnosed) were found in the literature. Median
      age at presentation was 37 years (interquartile range, 19-53) and 56% were women.
      Median progression of symptoms was 6 hours (interquartile range, 5-60 h),
      predominantly affecting the cervical spine (48%) by an arterial embolic source
      (56%). CONCLUSIONS: FCE is an unusual cause of spinal cord and cerebral ischemia
      with unknown incidence. Implementation of diagnostic imaging techniques and
      initial management of acute spinal disorders care in intensive care units might
      increase the incidence of disease antemortem. FCE should be considered in the
      differential diagnosis of ischemic spinal cord injury when no other causes can be
      identified and especially when the onset is progressive over several hours.

PMID- 24901880
TI  - Meta-analysis of circumferential fusion versus posterolateral fusion in lumbar
      spondylolisthesis.
AB  - STUDY DESIGN: Literature review and meta-analysis. SUMMARY OF BACKGROUND DATA:
      Posterolateral fusion (PLF) and circumferential fusion (CF) were widely used in
      the treatment of lumbar spondylolisthesis. There was a great controversy over the
      preferred fusion method. OBJECTIVE: We performed a meta-analysis for determining
      which fusion method was better in lumbar spondylolisthesis. METHODS: A systematic
      search was conducted in MEDLINE, EMBASE, and the Cochrane Collaboration Library
      from January 1960 to December 2013. Comparative studies were selected according
      to eligibility criteria. Weighed mean differences (WMDs) and risk differences
      were calculated. The final strength of evidence was expressed as different levels
      recommended by the GRADE Working Group. RESULTS: Eight comparative studies were
      identified. There was less evidence that no significant difference was found
      between CF and PLF for clinical satisfaction [odds ratio (OR), 0.63; 95%
      confidence interval (95% CI), 0.30, 1.32; P=0.22)] and for complication rate (OR,
      0.64; 95% CI, 0.23, 1.76; P=0.39). The PLF was more effective than the CF for the
      reduction of complication rate for patients with isthmic spondylolisthesis (OR,
      0.44; 95% CI, 0.23, 0.86; P=0.02). There was no significant difference for fusion
      rate, reoperation rate, operating time, and blood loss. Subanalysis showed that
      the CF can increase the fusion rate of patients with isthmic spondylolisthesis
      (OR, 0.12; 95% CI, 0.01, 1.00; P=0.05). PLF was more effective than CF for the
      reduction in operating time (WMD=-75.68; 95% CI, -99.00, -52.37; P<0.00001), and
      CF was more effective than PLF for the restoration of segment lordosis, disk
      height, and spondylolisthesis. CONCLUSIONS: There was really no difference for
      clinical satisfaction, complication rate, fusion rate, reoperation rate,
      operating time, and blood loss. PLF can reduce complication rate and operating
      time. CF can improve fusion rate for individuals with isthmic spondylolisthesis
      and restore lumbar alignment. The level of evidence was low.

PMID- 24901883
TI  - CROI 2014: Basic science review.
AB  - In the HIV basic science categories of the 2014 Conference on Retroviruses and
      Opportunistic Infections, research examining obstacles to viral eradication
      continued to be a major component. This research encompassed areas of activity
      from the identification of where virus resides in individuals on suppressive
      antiretroviral therapy to studies aimed at eliminating long-lived viral
      reservoirs that persist in the face of therapy. In the area of antiviral
      restrictions, a number of presentations highlighted the ability of host factors
      to profoundly shape the interplay between virus and host and, in particular, how
      innate immune response opposes viral infection through the induction of antiviral
      restrictions. 

PMID- 24901881
TI  - Occurrence and characterization of Shiga toxin-producing Escherichia coli O157:H7
      and other non-sorbitol-fermenting E. coli in cattle and humans in urban areas of
      Morogoro, Tanzania.
AB  - Escherichia coli strains such as Shiga toxin-producing E. coli (STEC),
      enteropathogenic E. coli, enterotoxigenic, attaching, and effacing E. coli, and
      enteroinvasive E. coli cause diarrhea in humans. Although other serotypes exist,
      the most commonly reported STEC in outbreaks is O157:H7. A cross-sectional study
      was conducted to isolate and characterize non-sorbitol-fermenting (NSF) E. coli
      O157:H7 from urban and periurban livestock settings of Morogoro, Tanzania. Human
      stool, cattle feces, and soil and water samples were collected. Observations and
      questionnaire interview studies were used to gather information about cattle and
      manure management practices in the study area. E. coli were isolated on sorbitol
      MacConkey agar and characterized by conventional biochemical tests. Out of 1049
      samples, 143 (13.7%) yielded NSF E. coli. Serological and antimicrobial tests and
      molecular typing were performed to NSF E. coli isolates. These procedures
      detected 10 (7%) pathogenic E. coli including STEC (n=7), enteropathogenic E.
      coli (EPEC) (n=2), and attaching and effacing E. coli (A/EEC) (n=1) strains. The
      STEC strains had the ability to produce VT1 and different VT2 toxin subtypes that
      caused cytopathic effects on Vero cells. The prevalence of STEC in cattle was
      1.6%, out of which 0.9% was serotype O157:H7 and the overall prevalence of
      diarrheagenic E. coli in cattle was 2.2%. The serotypes O157:H7, O142:H34,
      O113:H21, O+:H-, O+:H16, and O25:H4 were identified. One ESBL-producing isolate
      showed the MLST type ST131. To our knowledge, this is the first finding in
      Tanzania of this recently emerged worldwide pandemic clonal group, causing
      widespread antimicrobial-resistant infections, and adds knowledge of the
      geographical distribution of ST131. Cattle manure was indiscriminately deposited
      within residential areas, and there was direct contact between humans and cattle
      feces during manure handling. Cattle and manure management practices expose
      humans, animals, and the environment to pathogenic E. coli and other manure-borne
      pathogens. Therefore, there is a need to improve manure management practices in
      urban and periurban areas to prevent pathogen spread and associated human health
      risks.

PMID- 24901882
TI  - "Our hands are tied up": current state of safer conception services suggests the
      need for an integrated care model.
AB  - We conducted in-depth interviews with a variety of health care providers (n = 33)
      in Uganda to identify current services that could support and act as barriers to
      the provision of safer conception counseling (SCC). Consistent with their
      training and expertise, providers of all types reported provision of services for
      people living with a diagnosis of HIV or AIDS who desire a child. Important
      barriers, including a lack of service integration, poor communication between
      stakeholders, and the absence of policy guidelines, were identified. Drawing on
      these data, we propose a model of integrated care that includes both SCC services
      and prevention of unplanned pregnancies. 

PMID- 24901884
TI  - CROI 2014: New tools to track the epidemic and prevent HIV infections.
AB  - As discussed at the 2014 Conference on Retroviruses and Opportunistic Infections
      (CROI), substantial advances have been achieved in using laboratory tools to
      track the leading edge of HIV transmissions globally. Phylogenetic and
      phylodynamic studies have identified clusters of new infections occurring along
      geographic routes and in different groups, including young men who have sex with
      men. New assays for detecting acute HIV infection are promising; however,
      additional strategies are needed to increase uptake of HIV testing in a number of
      populations. Globally, people who inject drugs face numerous barriers to
      accessing HIV prevention and treatment services and are in need of integrated
      approaches to deliver services, address stigma and discrimination, and reform
      drug policies. Young women and individuals in serodiscordant relationships
      continue to be at high risk for HIV acquisition. Injectable hormonal
      contraception with progestins may increase the risk of HIV infection. Bacterial
      vaginosis may also increase HIV acquisition and transmission. Additional evidence
      suggests antiretroviral therapy lowers HIV transmission in serodiscordant
      couples, but high levels of diagnosis, linkage, retention, and viral suppression
      are needed to reduce population-level HIV incidence. Several programs evaluating
      the implementation of preexposure prophylaxis (PrEP) have shown high uptake in
      the United States and resource-limited settings. As adherence is a crucial
      determinant of PrEP efficacy, long-acting PrEP agents are promising approaches
      being tested. 

PMID- 24901885
TI  - CROI 2014: Neurologic complications of HIV infection.
AB  - A shift in focus in the field of neuroHIV was clearly manifest at the 2014
      Conference on Retroviruses and Opportunistic Infections (CROI), where a major
      emphasis was on the milder forms of neurologic morbidity, including cognitive
      impairment, seen in well-treated patients. Mechanisms of this persistent
      abnormality were investigated, including extensive analysis of the prevalence and
      associations of persistent HIV detection in cerebrospinal fluid (CSF) and
      characterization of persistent CNS immune activation. Another key emphasis was
      the early establishment of HIV replication and inflammation within the central
      nervous system (CNS) and the potentially salutary effect of very early HIV
      diagnosis and treatment in protecting the CNS from HIV-related injury.
      Mitochondrial function was identified as a potential mediator of a number of
      aspects of HIV-associated CNS dysfunction, including neurotoxicity associated
      with efavirenz, host genetic determinants of HIV-associated neurocognitive
      disorders (HAND), associations with direct measures of mitochondria in CSF, and
      metabolomic screening of CSF in HIV-infected subjects and those with HAND. Many
      studies employed laboratory rather than neuropsychologic end points, with a major
      focus on CSF biomarkers. Overall, neuroHIV presentations at CROI 2014 provided
      new insights into pathogenesis and treatment of the CNS, raising new challenges
      for researchers and practitioners aiming to optimize the status of the brain in
      people living with HIV infection. 

PMID- 24901886
TI  - CROI 2014: Viral hepatitis and complications of HIV disease and antiretroviral
      therapy.
AB  - The remarkable advances in interferon-sparing, all-oral hepatitis C virus (HCV)
      treatment were a highlight of the 2014 Conference on Retroviruses and
      Opportunistic Infections (CROI). The backbone of the nucleotide inhibitor
      sofosbuvir and the nonstructural protein 5A (NS5A) inhibitor ledipasvir with an
      additional third agent (HCV protease inhibitor or HCV nonnucleoside reverse
      transcriptase inhibitor) led to a sustained virologic response (SVR) rate 12
      weeks after cessation of treatment of 95% to 100% after only 6 weeks of
      treatment. These results demonstrate the potential of combination directacting
      antiviral (DAA) therapy for abbreviated, well-tolerated, and highly effective HCV
      treatment. Two triple-drug regimens that comprised 12 weeks of an NS5A inhibitor,
      an HCV protease inhibitor, and a nonnucleoside inhibitor also resulted in SVRs of
      more than 90% in patients with HCV genotype 1. HIV coinfection does not appear to
      negatively impact response to DAA-based HCV therapy, as evidenced by similar
      response rates in HIV/HCV-coinfected patients compared with HCV-monoinfected
      patients receiving interferonsparing or -containing regimens. There was continued
      emphasis at CROI 2014 on non-AIDS complications of HIV infection, specifically
      cardiovascular disease, renal insufficiency, and bone and endocrine disorders
      that persist among patients with treated HIV disease and contribute to morbidity
      and mortality. Finally, new data on novel drugs and combinations for treatment of
      tuberculosis (TB), patient outcomes using new rapid TB diagnostics, and a short
      course TB prevention strategy were presented. 

PMID- 24901887
TI  - CROI 2014: Advances in antiretroviral therapy.
AB  - The 2014 Conference on Retroviruses and Opportunistic Infections (CROI)
      highlighted important advances in antiretroviral therapy, with an emphasis on HIV
      eradication strategies. Follow-up information about the Mississippi baby who
      remains free of HIV infection off antiretroviral therapy was presented, and a
      second baby and 1 adult may also have been cured with very early initiation of
      antiretroviral therapy. The HIV care cascade was again a major focus of the
      conference. Investigators from around the world presented data on the
      implementation, and limitations, of the care cascade paradigm. Scale-up of
      antiretroviral therapy continues and a number of presentations featured optimal
      ways to measure the impact of these efforts by applying lessons from
      implementation science and health care economics. Encouraging results from
      expanded prevention of mother-to-child transmission programs, especially Option
      B+, were highlighted. Extensive data on transmitted (primary) drug resistance in
      the United States and Europe were presented. 

PMID- 24901888
TI  - Room temperature spontaneous conversion of OCS to CO2 on the anatase TiO2
      surface.
AB  - High-resolution FT-IR spectroscopy combined with quantum chemical calculations
      was used to study the chemistry of OCS-disproportionation over the reduced
      surface of isotopically labelled, nanocrystalline TiO2. Analysis of the isotopic
      composition of the product gases has revealed that the reaction involves solely
      OCS molecules from the gas-phase. Using quantum chemical calculations we propose
      a plausible mechanistic scenario, in which two reduced Ti(3+) centres mediate the
      reaction of the adsorbed OCS molecules. 

PMID- 24901889
TI  - A new mechanism in the binding between Homer3 EVH1 domain and inositol 1,4,5
      trisphosphate receptor suppressor domain.
AB  - The suppressor domain of inositol 1,4,5 trisphosphate receptor (IP3R) has
      critical roles in regulating the calcium channel by interacting with many binding
      partners. The residue 49-53 (PPKKF) of the suppressor domain was suggested to be
      a canonical Homer EVH1 domain binding site and is also the first a part of
      calmodulin (CaM) binding site. As CaM-binding of the suppressor domain has been
      shown to involve large-scale conformational changes, we studied the binding
      characteristics of the Homer EVH1-suppressor domain with NMR spectroscopy and
      biochemical pull-down assays for mutants. Our data show that the suppressor
      domain employs the PPKKF motif in a similar but subtly different way compared to
      previously characterized interactions, and that the suppressor domain does not
      undergo large-scale conformational changes. Chemical shift assignments of the
      Homer3 EVH1 domain found that a new set of residues, located at the opposite side
      of the previously reported binding site, is also involved in binding, which was
      confirmed by mutant binding assays. Further analysis suggests that F40 in the new
      binding sites may have a critical role as a conformational lock-switch in Homer
      target binding. The proposed mechanism is implicated in the signaling network
      involving calcium channels. 

PMID- 24901890
TI  - Association between PTEN Gene IVS4 polymorphism and risk of cancer: a meta
      analysis.
AB  - BACKGROUND: Phosphatase and tensin homolog (PTEN) is a well established tumor
      suppressor gene. Recently, increasing studies investigated the association
      between PTEN IVS4 polymorphism (rs3830675) and risk of various types of cancer.
      However, the results from the individual studies were controversial. The aim of
      this meta-analysis was to elucidate whether PTEN IVS4 polymorphism was associated
      with cancer risk. METHODS: Databases including PubMed, Web of knowledge and
      Chinese National Knowledge Infrastructure (CNKI) were systematically searched to
      identify potentially eligible literatures. Odds ratios (OR) and their 95%
      confidence interval (CI) were used to assess the strength of association between
      PTEN IVS4 polymorphism and cancer risk. RESULTS: A total of seven case-control
      studies were finally included in this meta-analysis. The pooled analysis
      suggested that individuals with PTEN IVS4 (-/-) genotype were significantly
      associated with increased risk of cancer (OR = 1.45, 95% CI = 1.19-1.76, P<0.001)
      and subgroup of digestive tract cancer (OR = 1.67, 95% CI = 1.28-2.18, P<0.001)
      compared with (+/+) genotype. The allele analysis revealed that (-) allele was
      significantly associated with increased risk of cancer (OR = 1.30, 95% CI = 1.12
      1.50, P = 0.001) and subgroup of digestive tract cancer (OR = 1.42, 95% CI = 1.16
      1.74, P = 0.001) compared with (+) allele. No significant association was
      observed between PTEN IVS4 (+/-) genotype and risk of cancer. CONCLUSION: PTEN
      IVS4 (-/-) genotype was significantly associated with increased risk of cancer
      especially for digestive tract cancer compared with (+/+) genotype. The (-)
      allele of PTEN IVS4 (rs3830675) polymorphism was significantly associated with
      increased risk of cancer especially for digestive tract cancer compared with (+)
      allele. The recessive effect model and dominant effect model also demonstrated
      significant association between PTEN IVS4 (rs3830675) polymorphism and increased
      cancer risk especially for digestive tract cancer. Further large-scale and well
      designed studies regarding different ethnicities are still required to confirm
      the results of our meta-analysis.

PMID- 24901892
TI  - Di-, tri- and tetranuclear molecular vanadium phosphonates: a chloride
      encapsulated tetranuclear bowl.
AB  - The reaction of vanadium(III) trichloride with tert-butylphosphonic acid (t
      BuPO3H2) in the presence of 1,10-phenanthroline/2,2'-bipyridine as an ancillary
      ligand in acetonitrile at room temperature afforded two dinuclear dicationic
      vanadium(IV) complexes [(VO)2(phen)2{t-BuPO2(OH)}2(OH2)2].2Cl [1] and
      [(VO)2(bipy)2{t-BuPO2(OH)}2(OH2)2].2Cl [2]. On the other hand, when the reaction
      was carried out in methanol, the dinuclear vanadium(V) complex [(VO)2(bipy)2(MU2
      O)2(t-BuPO3)2].2CH3OH.0.5CH2Cl2 [3] was isolated. While 1 and 2 contain two six
      membered V2P2O4 rings, 3 contains a unique four-membered V2O2 ring. Replacement
      of tert-butylphosphonic acid by tritylphosphonic acid (Ph3CPO3H2) under the same
      reaction conditions in methanol leads to the formation of dicationic trinuclear
      vanadium(IV) complexes [(VO)3(phen)3(Ph3CPO3)2(OH2)3].CHCl3.2(OH).2MeOH.1.5H2O
      [4] and [(VO)3(bipy)3(Ph3CPO3)2(CH3OH)3].2(OH).4CH3OH.5H2O [5]. In these
      complexes, the triangular V(IV) platform is held together by two bicapping
      tripodal phosphonate ligands. Replacement of the chelating 2,2'-bipyridine ligand
      with 3,5-dimethyl-1H-pyrazole, under the same reaction conditions, afforded a
      tetranuclear vanadium(V) complex [{(VO)4(Ph3CPO3Me)4(MU-O)4}Cl]{3,5
      Me2PzH2}.3C7H8.H2O.CH3OH [6]. Remarkably 6 possesses a unique bowl-shaped
      structure encapsulating a chloride anion.

PMID- 24901891
TI  - 'As many options as there are, there are just not enough for me': contraceptive
      use and barriers to access among Australian women.
AB  - OBJECTIVE: A comprehensive life course perspective of women's experiences in
      obtaining and using contraception in Australia is lacking. This paper explores
      free-text comments about contraception provided by women born between 1973 and
      1978 who participated in the Australian Longitudinal Study on Women's Health
      (ALSWH). METHODS: The ALSWH is a national population-based cohort study involving
      over 40,000 women from three age groups, who are surveyed every three years. An
      initial search identified 1600 comments from 690 women across five surveys from
      1996 (when they were aged 18-23 years) to 2009 (31-36 years). The analysis
      included 305 comments from 289 participants. Factors relating to experiences of
      barriers to access and optimal contraceptive use were identified and explored
      using thematic analysis. RESULTS: Five themes recurred across the five surveys as
      women aged: (i) side effects affecting physical and mental health; (ii) lack of
      information about contraception; (iii) negative experiences with health services;
      (iv) contraceptive failure; and (v) difficulty with accessing contraception.
      CONCLUSION: Side effects of hormonal contraception and concerns about
      contraceptive failure influence women's mental and physical health. Many barriers
      to effective contraception persist throughout women's reproductive lives. Further
      research is needed into reducing barriers and minimising negative experiences, to
      ensure optimal contraceptive access for Australian women.

PMID- 24901893
TI  - Non-cutaneous melanoma: is there a role for (18)F-FDG PET-CT?
AB  - Non-cutaneous melanomas (NCM) are diverse and relatively uncommon. They often
      differ from cutaneous melanomas in their epidemiology, genetic profile and
      biological behaviour. Despite the growing body of evidence regarding the utility
      of positron emission tomography (PET)/CT in cutaneous melanoma, the data on its
      use in NCM are scarce. In this review, we will summarize the existing literature
      and present cases from our experience with NCM to illustrate current knowledge on
      the potential role and limitations of fluorine-18 fludeoxyglucose PET/CT in NCM. 

PMID- 24901894
TI  - Risk factors for extended spectrum beta-lactamase-producing Escherichia coli
      versus susceptible E. coli in surgical site infections among cancer patients in
      Mexico.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli
      are of increasing concern as a cause of healthcare-associated infections. STUDY
      DESIGN: Using a matched case-control design, demographics, antibiotic use, and
      relevant surgical data were obtained for 173 cases (ESBL E. coli surgical site
      infections, [SSI]) and 173 controls (antibiotic-susceptible E. coli SSI) in an
      oncology hospital in Mexico City. Conditional logistic regression modeling was
      used to calculate odds ratios (OR). RESULTS: The mean age of patients was 53.6
      years, 214 (62%) were female. Demographics and comorbidities were similar between
      groups. Although antibiotic prophylaxis was common among both cases and controls
      (84% and 89%), more than one-half of cases (53%) were given prophylaxis outside
      the recommended window or were exposed for more than 24 h in comparison to 29% of
      controls. Patients who received untimely (OR=3.13, 95% confidence interval [CI]
      1.5-6.4) and discontinued inappropriately (OR 6.38, 95% CI=2.5-16.2) prophylaxis
      were more likely to develop an ESBL SSI. In addition, patients with an
      organ/space infection compared with superficial had a higher rate of a resistant
      infection (OR 4.2, 95% CI 1.3-13.9). Among patients not given timely or
      appropriately discontinued prophylaxis, post-operative cephalosporin use (OR 3.3,
      95% CI 1.4-7.7) was associated with ESBL E. coli SSIs. CONCLUSIONS: The
      appropriate timing and duration of perioperative antimicrobial prophylaxis were
      associated with lower risk of ESBL E. coli in SSIs. Even though compliance to
      antimicrobial prophylaxis guidelines is of the utmost importance, reduced
      exposure to cephalosporins may also potentially decrease the risk of ESBL SSI.

PMID- 24901895
TI  - Impact of lower body negative pressure induced hypovolemia on peripheral venous
      pressure waveform parameters in healthy volunteers.
AB  - Lower body negative pressure (LBNP) creates a reversible hypovolemia by
      sequestrating blood volume in the lower extremities. This study sought to examine
      the impact of central hypovolemia on peripheral venous pressure (PVP) waveforms
      in spontaneously breathing subjects. With IRB approval, 11 healthy subjects
      underwent progressive LBNP (baseline, -30, -75, and -90 mmHg or until the subject
      became symptomatic). Each was monitored for heart rate (HR), finger arterial
      blood pressure (BP), a chest respiratory band and PVP waveforms which are
      generated from a transduced upper extremity intravenous site. The first subject
      was excluded from PVP analysis because of technical errors in collecting the
      venous pressure waveform. PVP waveforms were analyzed to determine venous pulse
      pressure, mean venous pressure, pulse width, maximum and minimum slope (time
      domain analysis) together with cardiac and respiratory modulations (frequency
      domain analysis). No changes of significance were found in the arterial BP values
      at -30 mmHg LBNP, while there were significant reductions in the PVP waveforms
      time domain parameters (except for 50% width of the respiration induced
      modulations) together with modulation of the PVP waveform at the cardiac
      frequency but not at the respiratory frequency. As the LBNP progressed, arterial
      systolic BP, mean BP and pulse pressure, PVP parameters and PVP cardiac
      modulation decreased significantly, while diastolic BP and HR increased
      significantly. Changes in hemodynamic and PVP waveform parameters reached a
      maximum during the symptomatic phase. During the recovery phase, there was a
      significant reduction in HR together with a significant increase in HR
      variability, mean PVP and PVP cardiac modulation. Thus, in response to mild
      hypovolemia induced by LBNP, changes in cardiac modulation and other PVP waveform
      parameters identified hypovolemia before detectable hemodynamic changes. 

PMID- 24901896
TI  - Signals for color and achromatic contrast in the goldfish inner retina.
AB  - A moving stimulus paradigm was designed to investigate color contrast encoding in
      the retina. Recently, this paradigm yielded suggestive evidence for color
      contrast encoding in zebrafish but the significance and generality remain
      uncertain since the properties of color coding in the zebrafish inner retina are
      largely unknown. Here, the question of color contrast is pursued in the goldfish
      retina where there is much accumulated evidence for retinal mechanisms of color
      vision and opponent color-coding, in particular. Recordings of a sensitive local
      field potential of the inner retina, the proximal negative response, were made in
      the intact, superfused retina in the light-adapted state. Responses to color
      contrast and achromatic contrast were analyzed by comparing responses to a green
      moving bar on green versus red backgrounds. The quantitative form of the
      irradiance/response curves was distinctly different under a range of conditions
      in 32 retinas, thereby providing robust evidence for red-green color contrast.
      The color contrast is based on successive contrast, occurs in the absence of
      overt color opponency, and clearly differs from previous findings in the goldfish
      retina for simultaneous color contrast mediated by color-opponent neurons. The
      form of the irradiance/response curves suggests that successive color contrast is
      particularly important when achromatic contrast is low, as often occurs in
      natural environments. The present results provide a parallel with the well-known
      principle of human color vision, first proposed by Kirschmann as the third law of
      color contrast, and may also have implications for the evolution of vertebrate
      color vision. 

PMID- 24901898
TI  - C K-edge NEXAFS spectra of graphene with physical and chemical defects: a study
      based on density functional theory.
AB  - Recently, C K-edge Near Edge X-ray Absorption Fine Structure (NEXAFS) spectra of
      graphite (HOPG) surfaces have been measured for the pristine material, and for
      HOPG treated with either bromine or krypton plasmas (Lippitz et al., Surf. Sci.,
      2013, 611, L1). Changes of the NEXAFS spectra characteristic for physical
      (krypton) and/or chemical/physical modifications of the surface (bromine) upon
      plasma treatment were observed. Their molecular origin, however, remained
      elusive. In this work we study by density functional theory, the effects of
      selected point and line defects as well as chemical modifications on NEXAFS
      carbon K-edge spectra of single graphene layers. For Br-treated surfaces, also Br
      3d X-ray Photoelectron Spectra (XPS) are simulated by a cluster approach, to
      identify possible chemical modifications. We observe that some of the defects
      related to plasma treatment lead to characteristic changes of NEXAFS spectra,
      similar to those in experiment. Theory provides possible microscopic origins for
      these changes. 

PMID- 24901897
TI  - Psychological covariates of longitudinal changes in back-related disability in
      patients undergoing acupuncture.
AB  - OBJECTIVES: To identify psychological covariates of longitudinal changes in back
      related disability in patients undergoing acupuncture. MATERIALS AND METHODS: A
      longitudinal postal questionnaire study was conducted with data collection at
      baseline (pretreatment), 2 weeks, 3, and 6 months later. A total of 485 patients
      were recruited from 83 acupuncturists before commencing acupuncture for back
      pain. Questionnaires measured variables from 4 theories (fear-avoidance model,
      common-sense model, expectancy theory, social-cognitive theory), clinical and
      sociodemographic characteristics, and disability. Longitudinal multilevel models
      were constructed with disability over time as the outcome. RESULTS: Within
      individuals, reductions in disability (compared with the person's individual
      mean) were associated with reductions in: fear-avoidance beliefs about physical
      activity (beta=0.11, P<0.01) and work (beta=0.03, P<0.05), catastrophizing
      (beta=0.28, P<0.05), consequences (beta=0.28, P<0.01), concerns (beta=0.17,
      P<0.05), emotions (beta=0.16, P<0.05), and pain identity (beta=0.43, P<0.01).
      Within-person reductions in disability were associated with increases in:
      personal control (beta=-0.17, P<0.01), comprehension (beta=-0.11, P<0.05) and
      self-efficacy for coping (beta=-0.04, P<0.01). Between individuals, people who
      were less disabled had weaker fear-avoidance beliefs about physical activity
      (beta=0.12, P<0.01), had more self-efficacy for coping (beta=-0.07, P<0.01),
      perceived less severe consequences of back pain (beta=0.87, P<0.01), had more
      positive outcome expectancies (beta=-0.30, P<0.05), and appraised acupuncture
      appointments as less convenient (beta=0.92, P<0.05). DISCUSSION: Illness
      perceptions and, to a lesser extent, self-efficacy and expectancies can usefully
      supplement variables from the fear-avoidance model in theorizing pain-related
      disability. Positive changes in patients' beliefs about back pain might underpin
      the large nonspecific effects of acupuncture seen in trials and could be targeted
      clinically.

PMID- 24901899
TI  - The mammary gland in small ruminants: major morphological and functional events
      underlying milk production--a review.
AB  - The importance of small ruminants to the dairy industry has increased in recent
      years, especially in developing countries, where it has a high economic and
      social impact. Interestingly and despite the fact that the mammary gland is the
      specialised milk production organ, very few authors studied the modifications
      occurring in the mammary gland through the lactation period in production
      animals, particularly in the small ruminants, sheep (Ovis aries) and goat (Capra
      hircus). Nevertheless, understanding the different mammary gland patterns
      throughout lactation is essential to improve dairy production. In addition,
      associating these patterns with different milking frequencies, lactation number
      or different diets is also of high importance, directly affecting the dairy
      industry. The mammary gland is commonly composed of parenchyma and stroma, which
      includes the ductal system, with individual proportions of each changing during
      the different periods and yields in a lactation cycle. Indeed, during late
      gestation, as well as during early to mid-lactation, mammary gland expansion
      occurs, with an increase in the number of epithelial cells and lumen area, which
      leads to increment of the parenchyma tissue, as well as a reduction of stroma,
      corresponding macroscopically to the increase in mammary gland volume. Throughout
      late lactation, the mammary gland volume decreases owing to the regression of the
      secretory structure. In general, common mammary gland patterns have been shown
      for both goats and sheep throughout the several lactation stages, although the
      number of studies is limited. The main objective of this manuscript is to review
      the colostrogenesis and lactogenesis processes as well as to highlight the
      mammary gland morphological patterns underlying milk production during the
      lactation cycle for small ruminants, and to describe potential differences
      between goats and sheep, hence contributing to a better description of mammary
      gland development during lactation for these two poorly studied species. 

PMID- 24901900
TI  - Feasibility and effectiveness of a web-based positive psychology program for
      youth mental health: randomized controlled trial.
AB  - BACKGROUND: Youth mental health is a significant public health concern due to the
      high prevalence of mental health problems in this population and the low rate of
      those affected seeking help. While it is increasingly recognized that prevention
      is better than cure, most youth prevention programs have utilized interventions
      based on clinical treatments (eg, cognitive behavioral therapy) with inconsistent
      results. OBJECTIVE: This study explores the feasibility of the online delivery of
      a youth positive psychology program, Bite Back, to improve the well-being and
      mental health outcomes of Australian youth. Further aims were to examine rates of
      adherence and attrition, and to investigate the program's acceptability. METHODS:
      Participants (N=235) aged 12-18 years were randomly assigned to either of two
      conditions: Bite Back (n=120) or control websites (n=115). The Bite Back website
      comprised interactive exercises and information across a variety of positive
      psychology domains; the control condition was assigned to neutral entertainment
      based websites that contained no psychology information. Participants in both
      groups were instructed to use their allocated website for 6 consecutive weeks.
      Participants were assessed pre- and postintervention on the Depression Anxiety
      Stress Scale-Short form (DASS-21) and the Short Warwick-Edinburgh Mental Well
      Being Scale (SWEMWBS). RESULTS: Of the 235 randomized participants, 154 (65.5%)
      completed baseline and post measures after 6 weeks. Completers and dropouts were
      equivalent in demographics, the SWEMWBS, and the depression and anxiety subscales
      of the DASS-21, but dropouts reported significantly higher levels of stress than
      completers. There were no differences between the Bite Back and control
      conditions at baseline on demographic variables, DASS-21, or SWEMWBS scores.
      Qualitative data indicated that 49 of 61 Bite Back users (79%) reported positive
      experiences using the website and 55 (89%) agreed they would continue to use it
      after study completion. Compared to the control condition, participants in the
      Bite Back condition with high levels of adherence (usage of the website for 30
      minutes or more per week) reported significant decreases in depression and stress
      and improvements in well-being. Bite Back users who visited the site more
      frequently (>=3 times per week) reported significant decreases in depression and
      anxiety and improvements in well-being. No significant improvements were found
      among Bite Back users who demonstrated low levels of adherence or who used the
      website less frequently. CONCLUSIONS: Results suggest that using an online
      positive psychology program can decrease symptoms of psychopathology and increase
      well-being in young people, especially for those who use the website for 30
      minutes or longer per week or more frequently (>=3 times per week). Acceptability
      of the Bite Back website was high. These findings are encouraging and suggest
      that the online delivery of positive psychology programs may be an alternate way
      to address mental health issues and improve youth well-being nationally. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN1261200057831;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362489 (Archived
      by Webcite at http://www.webcitation.org/6NXmjwfAy).

PMID- 24901901
TI  - A Rare Case of Sunitinib-Induced Hyperammonemic Encephalopathy and Hypothyroidism
      in Metastatic Renal Cell Carcinoma.
AB  - Sunitinib has become a standard treatment agent for metastatic renal cell
      carcinoma (RCC) for several years. However, various adverse events have been
      reported. We present a rare adverse effect of hyperammonemic encephalopathy
      induced by sunitinib. A 66-year-old woman with metastatic RCC referred to the
      emergency department with confusion that developed 14 days after the initiation
      of 50 mg/d of sunitinib. Her serum ammonia and thyroid-stimulating hormone levels
      were markedly elevated (146 MUg/dL and 27.27 MUIU/mL, respectively). Sunitinib
      was discontinued, and an enema with lactulose and L-thyroxine were administered.
      Her mental status and neurologic symptoms were normalized 7 days after the
      treatment. Serum ammonia level decreased to 61 MUg/dL and thyroid stimulating
      hormone level decreased 22.34 MUIU/mL. The incidence of sunitinib-induced
      hyperammonemia is rarely reported. The relationship between sunitinib and the
      development of hyperammonemia is not well understood, and the mechanism is
      unclear. Sunitinib-induced hyperammonemia is very rare, and to the best of our
      knowledge, this is fourth case hyperammonemia and first case hyperammonemic
      encephalopathy with hypothyroidism as an adverse effect. Therefore, it is
      important for clinicians to be aware of hyperammonemia that can occur in several
      days after the initiation of sunitinib treatment in metastatic RCC. 

PMID- 24901902
TI  - The Influence of Cholesterol on Fast Dynamics Inside of Vesicle and Planar
      Phospholipid Bilayers Measured with 2D IR Spectroscopy.
AB  - Phospholipid bilayers are frequently used as models for cell membranes. Here the
      influence of cholesterol on the structural dynamics in the interior of 1,2
      dilauroyl-sn-glycero-3-phosphocholine (dilauroylphosphatidylcholine, DLPC)
      vesicles and DLPC planar bilayers are investigated as a function of cholesterol
      concentration. 2D IR vibrational echo spectroscopy was performed on the
      antisymmetric CO stretch of the vibrational probe molecule tungsten hexacarbonyl,
      which is located in the interior alkyl regions of the bilayers. The 2D IR
      experiments measure spectral diffusion, which is caused by the structural
      fluctuations of the bilayers. The 2D IR measurements show that the bilayer
      interior alkyl region dynamics occur on time scales ranging from a few
      picoseconds to many tens of picoseconds. These are the time scales of the
      bilayers' structural dynamics, which act as the dynamic solvent bath for chemical
      processes of membrane biomolecules. The results suggest that at least a
      significant fraction of the dynamics arise from density fluctuations. Samples are
      studied in which the cholesterol concentration is varied from 0% to 40% in both
      the vesicles (72 nm diameter) and fully hydrated planar bilayers in the form of
      aligned multibilayers. At all cholesterol concentrations, the structural dynamics
      are faster in the curved vesicle bilayers than in the planar bilayers. As the
      cholesterol concentration is increased, at a certain concentration there is a
      sudden change in the dynamics, that is, the dynamics abruptly slow down. However,
      this change occurs at a lower concentration in the vesicles (between 10% and 15%
      cholesterol) than in the planar bilayers (between 25% and 30% cholesterol). The
      sudden change in the dynamics, in addition to other IR observables, indicates a
      structural transition. However, the results show that the cholesterol
      concentration at which the transition occurs is influenced by the curvature of
      the bilayers. 

PMID- 24901903
TI  - New techniques for producing transgenic animals - a mixed blessing from both the
      scientific and animal welfare perspectives.

PMID- 24901904
TI  - ESNATS conference - the use of human embryonic stem cells for novel toxicity
      testing approaches.
AB  - The main achievements and results of the ESNATS project (Embryonic Stem Cell
      based Novel Alternative Testing Strategies) were presented at the final project
      conference that was held on 15 September 2013, the day before the traditional
      EUSAAT (European Society for Alternatives to Animal Testing) Congress in Linz,
      Austria. The ESNATS project was an FP7 European Integrated Project, running from
      2008 to 2013, the aim of which was to develop a novel toxicity testing platform
      based on embryonic stem cells (ESCs), and in particular, human ESC (hESCs), to
      accelerate drug development, reduce related R&D costs, and propose a powerful
      alternative to animal tests in the spirit of the Three Rs principles. Altogether,
      ESNATS offered the first proof of concept that hESCs can be used to create
      robust, reproducible and ready-to-use test assays for predicting human toxicity.
      In the end, essentially five test systems were developed to an adequate level for
      entering possible pre-validation procedures. These methods are based on hESCs,
      and can be combined to study the possible effects, on the human embryo, of
      exposure to a chemical during the early stages of development. In addition to the
      presentations by the main project partners, external speakers were invited to
      give lectures on relevant topics, both in the field of neurotoxicity and, more
      generally, on the applicability of hESCs in the development of advanced in vitro
      tests. 

PMID- 24901905
TI  - A tutorial for analysing the cost-effectiveness of alternative methods for
      assessing chemical toxicity: the case of acute oral toxicity prediction.
AB  - Compared with traditional animal methods for toxicity testing, in vitro and in
      silico methods are widely considered to permit a more cost-effective assessment
      of chemicals. However, how to assess the cost-effectiveness of alternative
      methods has remained unclear. This paper offers a user-oriented tutorial for
      applying cost-effectiveness analysis (CEA) to alternative (non-animal) methods.
      The purpose is to illustrate how CEA facilitates the identification of the
      alternative method, or the combination of methods, that offers the highest
      information gain per unit of cost. We illustrate how information gains and costs
      of single methods and method combinations can be assessed. By using acute oral
      toxicity as an example, we apply CEA to a set of four in silico methods
      (ToxSuite, TOPKAT, TEST, ADMET Predictor), one in vitro method (the 3T3 Neutral
      Red Uptake cytotoxicity assay), and various combinations of these methods. Our
      results underline that in silico tools are more cost-effective than the in vitro
      test. Battery combinations of alternative methods, however, do not necessarily
      outperform single methods, because additional information gains from the battery
      are easily outweighed by additional costs. 

PMID- 24901906
TI  - A survey of knowledge of the three Rs concept among lecturers and postgraduate
      students in Brazil.
AB  - The use of animals in science is a widespread practice, despite growing concern
      about its moral justification and scientific relevance. In this scenario, the
      Three Rs concept might be considered to be a motivation for the establishment of
      a new scientific approach to the use of experimental animals and to research
      itself. The main objective of this survey-based study was to identify the level
      of knowledge about this concept among lecturers (i.e. tenure-track professors)
      and postgraduate students in the physiological and pharmaceutical sciences in
      Brazilian universities. A questionnaire was completed by 185 lecturers from 16
      universities, and 140 postgraduate students from five of these universities. The
      results indicate that the concept of the Three Rs is widespread among lecturers
      and students in the areas of physiology and pharmacology, throughout Brazilian
      universities, but that its interpretation generally attributes more importance to
      refinement than to reduction and replacement. 

PMID- 24901907
TI  - Every silver lining has a cloud: the scientific and animal welfare issues
      surrounding a new approach to the production of transgenic animals.
AB  - The scientific basis and advantages of using recently developed CRISPR/Cas-9
      technology for transgenesis have been assessed with respect to other production
      methods, laboratory animal welfare, and the scientific relevance of transgenic
      models of human diseases in general. As the new technology is straightforward,
      causes targeted DNA double strand breaks and can result in homozygous changes in
      a single step, it is more accurate and more efficient than other production
      methods and speeds up transgenesis. CRISPR/Cas-9 also obviates the use of
      embryonic stem cells, and is being used to generate transgenic non-human primates
      (NHPs). While the use of this method reduces the level of animal wastage
      resulting from the production of each new strain, any long-term contribution to
      reduction will be offset by the overall increase in the numbers of transgenic
      animals likely to result from its widespread usage. Likewise, the contribution to
      refinement of using a more-precise technique, thereby minimising the occurrence
      of unwanted genetic effects, will be countered by a probable substantial increase
      in the production of transgenic strains of increasingly sentient species. For
      ethical and welfare reasons, we believe that the generation of transgenic NHPs
      should be allowed only in extremely exceptional circumstances. In addition, we
      present information, which, on both welfare and scientific grounds, leads us to
      question the current policy of generating ever-more new transgenic models in
      light of the general failure of many of them, after over two decades of
      ubiquitous use, to result in significant advances in the understanding and
      treatment of many key human diseases. Because this unsatisfactory situation is
      likely to be due to inherent, as well as possibly avoidable, limitations in the
      transgenic approach to studying disease, which are briefly reviewed, it is
      concluded that a thorough reappraisal of the rationale for using genetically
      altered animals in fundamental research and by the pharmaceutical industry, and
      for its support by funding bodies, should be undertaken. In the meantime, the use
      of CRISPR/Cas-9 to generate new transgenic cells in culture is to be guardedly
      encouraged. 

PMID- 24901908
TI  - Locating the middle ground.

PMID- 24901909
TI  - Assessing the effects of environmental enrichment on behavioural deficits in
      C57BL mice.

PMID- 24901910
TI  - The use of lower organisms.

PMID- 24901911
TI  - Cross-cultural adaptation, reliability and validity of the Turkish version of the
      Hospital for Special Surgery (HSS) Knee Score.
AB  - OBJECTIVE: The purpose of this study was to adapt the English version of the
      Hospital for Special Surgery (HSS) knee score for use in a Turkish population and
      to evaluate its validity, reliability and cultural adaptation. METHODS: Standard
      forward-back translation of the HSS knee score was performed and the Turkish
      version was applied in 73 patients. The Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC), Mini-Mental State Examination and sit-to-stand test
      were also performed and analyzed. Internal consistency reliability was tested
      using Cronbach's alpha. The intraclass correlation coefficient (ICC) was used to
      calculate the test-retest reliability at one-week intervals. Validity was
      assessed by calculating the Pearson correlation between the HSS, WOMAC and sit-to
      stand test scores. RESULTS: The ICC ranged from 0.98 to 0.99 with high internal
      consistency (Cronbach's alpha: 0.87). The WOMAC score correlated with total HSS
      score (r: -0.80, p<0.001) and sit-to-stand score (r: 0.12, p: 0.312). CONCLUSION:
      The Turkish version of the HSS knee score is reliable and valid in evaluating the
      total knee arthroplasty in Turkish patients.

PMID- 24901912
TI  - Missed isolated posterior malleolar fractures.
AB  - OBJECTIVE: The aim of this study was to evaluate the injury mechanism and
      clinical and radiological results of the patients with isolated posterior
      malleolar fracture. METHODS: Seven patients (5 male, 2 female; mean age: 32
      years; range: 23-40) with a missed isolated posterior malleolar fracture were
      included in the study. All patients had initially been examined for an ankle
      sprain in the emergency room, where the initial plain radiographs did not show
      any abnormality. Due to the long lasting symptoms all patients underwent an MRI
      scan by the 3rd week which revealed a posterior malleolar fracture. Patients were
      treated with an ankle brace for 3 weeks. All patients were followed up for 1
      year. Bone healing and degenerative changes were evaluated with plain
      Radiographs, including a 50 degrees  external rotation lateral. Clinical outcome
      was evaluated with American Orthopedic Foot and Ankle Society ankle hindfoot
      scale. RESULTS: Fracture healing was seen in 6 of the 7 patients by the 6th week.
      There was no radiographic healing by 6th month in the remaining patient. Mean
      AOFAS ankle hindfoot scores at the beginning of the treatment and at 3rd month
      were 20 (11-31) and 86 (43-96), respectively. There was no instability or
      degenerative changes at one-year follow-up. CONCLUSION: Isolated posterior
      malleolar fracture should be kept in mind in patients who present with pain at
      the posterior part of the ankle following a forced plantar flexion and/or axial
      compression injury. A 50 degrees  external rotation lateral radiograph can be
      useful in detecting the fracture.

PMID- 24901913
TI  - Evaluation of surgical and non-surgical interventions for clavicle fractures.
AB  - OBJECTIVE: The aim of this study was to review all systematic reviews and meta
      analyses and provide an overview of the evidence of efficacy of interventions for
      clavicle fractures. METHODS: The Cochrane Library, PubMed, MEDLINE, Chinese
      Biomedicine database, China Academic Journals Full-text Database, VIP Chinese
      Science and Technology Periodicals Database and Wanfang Database were searched
      for eligible studies using keywords related to clavicle fractures. The
      methodological quality of included studies was assessed using the AMSTAR
      assessment tool. Direct evidence was analyzed narratively. Randomized controlled
      trials were pooled again for meta-analysis. The GRADE approach was used in
      summary conclusions. RESULTS: The result of pooled data showed that while
      operative treatment had lower nonunion and malunion rates and higher patient
      satisfaction than non-operative treatment modalities [RR=6.57, 95% CI (3.01,
      14.35), RR=6.93, 95% CI (2.99, 16.09); RR=0.68, 95% CI (0.51, 0.90)], these 3
      outcomes were based on low-quality evidence. There was no difference between
      dissimilar operative and dissimilar non-operative treatments. CONCLUSION:
      Operative treatment is more effective than non-operative treatment in terms of
      nonunion and malunion rates and patient satisfaction. As the quality of evidence
      comparing efficacy between intervention methods is generally low, further
      original studies are needed.

PMID- 24901914
TI  - Component alignment in total wrist arthroplasty: success rate of surgeons in
      their first cases.
AB  - OBJECTIVE: The aim of this study was to assess the probability of achieving a
      satisfactory alignment in the performance of a first wrist arthroplasty. METHODS:
      The total wrist arthroplasties (ReMotion(r)) of 14 wrists of 7 corpses performed
      by 14 inexperienced surgeons were reviewed radiologically. Radial component
      alignment in the posteroanterior view (RCA-PA), radial component alignment in the
      lateral view (RCA-Lat), carpal component alignment in the posteroanterior view
      (CCA-PA) and carpal component alignment in lateral view (CCA-Lat) were measured.
      RESULTS: Mean RCA-PA angle was 9.6o, mean RCA-Lat angle 4.6o, mean CCA-PA angle
      4.4o and mean CCA-Lat angle 10.1o. None of the arthroplasties had a satisfactory
      alignment. CONCLUSION: It is difficult for an inexperienced surgeon to achieve a
      correct component alignment in his/her first total wrist arthroplasty, especially
      in the carpal component. Therefore, we recommend that the position of the
      prosthesis is confirmed before securing it to the bone with the help of X-ray
      images.

PMID- 24901915
TI  - Treatment of diaphyseal forearm atrophic nonunions with intramedullary nails and
      modified Nicoll's technique in adults.
AB  - OBJECTIVE: The aim of this study was to evaluate the outcome of
      tricorticocancellous autologous bone grafting with intramedullary forearm nails
      in the treatment of radius or ulna aseptic nonunion. METHODS: The study included
      8 patients (mean age: 39 years; range: 19 to 55 years) who underwent plate-screw
      osteosynthesis for the treatment of nonunion (6 ulna, 2 radius) following forearm
      fracture. In all cases, the length of the applied tricortical graft was below 3
      cm. Patients were evaluated using the visual analog scale, Grace and Eversmann
      scale and DASH score. Wrist flexion and extension and postoperative hand and
      forearm grip strength were assessed. RESULTS: Graft incorporation and union was
      completed at a mean of 22 (range: 18 to 28) weeks. No patient had nonunion, deep
      infection or radioulnar synostosis. Follow-up ranged from 18 to 52 months.
      Radiographic union was achieved in all patients. Mean visual analog scale pain
      score was 1 (range: 0 to 3). Grace and Eversmann ratings were excellent in 5 and
      good in 3 patients. Mean DASH score was 10.7 (range: 1.7 to 21.7) points.
      CONCLUSION: Intramedullary nailing and tricorticocancellous iliac bone block
      grafting appears to be a technically easy and reliable procedure that enables
      early postoperative rehabilitation in the treatment of nonunion of the forearm.

PMID- 24901916
TI  - The extensor hallucis longus tendon as the distal reference point in total knee
      arthroplasty and tibial alignment.
AB  - OBJECTIVE: The aim of this study was to compare the effects on tibial alignment
      of the use of the extensor hallucis longus (EHL) tendon with the use of the 2nd
      metatarsal as a reference in total knee arthroplasty (TKA) using the
      extramedullary technique. METHODS: The study evaluated 100 postoperative
      radiographs of 79 patients who underwent primary TKA between 2004 and 2008.
      Patients were grouped according to the distal anatomical landmark used during
      surgery. There were 36 patients (mean age: 68.3 years, range: 56 to 82 years) in
      the EHL-referenced (ERT) group and 43 patients (mean age: 70.2 years, range: 54
      to 78 years) in the 2nd metatarsal-referenced (MRT) group. There were 47
      components in the ERT group and 53 in the MRT group. Frontal alignments of the
      tibial components were measured. Angles of 90+/-2 degrees  were accepted as the
      normal boundaries while those above that value were labeled as 'varus' and those
      below as 'valgus'. RESULTS: Average frontal alignment was 88.57 degrees  in the
      MRT group and 89.17 degrees  in the ERT group. The number of tibial components in
      the normal range was significantly higher (p=0.017) and the number of varus
      oriented components significantly lower (p=0.024) in the ERT group. There were no
      significant differences in valgus-oriented outliers between groups (p=1.000).
      CONCLUSION: The use of the EHL tendon as a reference improves coronal tibial
      alignment. The EHL is a reliable anatomical landmark to use with extramedullary
      guide systems.

PMID- 24901917
TI  - Arthroscopic characteristics of meniscal injuries in osteoarthritic knees.
AB  - OBJECTIVE: The aim of this study was to investigate the arthroscopic
      characteristics of meniscal injuries in osteoarthritic knees and explore their
      significance in the selection of surgical approach. METHODS: Four original types
      of meniscal injuries were defined. The study included 87 cases; 12 Type 1, 26
      Type 2, 35 Type 3 and 14 in Type 4 meniscal injuries. For Type 1 injuries, 5
      cases underwent meniscal suture repair and 7 cases partial meniscal resection.
      Partial meniscal resection was performed in 22 cases and subtotal resection in 4
      cases of Type 2 injury. For Type 3 injury, meniscal debridement was performed in
      2, partial resection in 8, subtotal resection in 19 and total resection in 6
      cases. For Type 4 injury, 3 cases underwent subtotal resection and 11 underwent
      total resection. Patients were evaluated with the Lysholm, visual analog scale,
      and Kellgren-Lawrence scale scores and cartilage lesions stages. RESULTS: Mean
      follow-up period was 26 (range: 8 to 51) months. Joint swelling or pain was
      present in 13 cases after fatigue. Twist lock symptom was observed in one Type 3
      injury and one Type 4 injury. Joint flexion was limited to 20 degrees  in one
      Type 3 injury and two Type 4 injuries. Total knee joint replacement was performed
      in two Type 2 and two Type 4 injuries 2 to 3 years and 2 months after surgery.
      CONCLUSION: The classification of meniscal injuries in osteoarthritic knees was
      designed to guide arthroscopic surgery and improve the therapeutic efficacy of
      minimally invasive surgery for knee osteoarthritis.

PMID- 24901918
TI  - The effect of progressive eccentric and concentric training on functional
      performance after autogenous hamstring anterior cruciate ligament reconstruction:
      a randomized controlled study.
AB  - OBJECTIVE: The aim of this study was to assess the functional results of an early
      onset progressive eccentric and concentric training in patients with autogen
      hamstring anterior cruciate ligament (ACL) reconstruction. METHODS: Thirty-three
      patients with autogenous hamstring ACL reconstruction were randomly divided into
      study (n=16, mean age; 33.87+/-8.19) and control (n=17, mean age; 32.64+/-8.21)
      groups and followed the same ACL rehabilitation program. Additionally, the study
      group followed a progressive eccentric and concentric training for 12 weeks on
      the Monitorized Functional Squat System (MFSS) beginning 3 weeks after surgery.
      The groups were compared according to the isokinetic strength of the knee
      extensors and flexors, functional performance (the vertical jump test, a single
      hop for distance test) and the Lysholm knee scale, the Anterior Cruciate Ligament
      Quality of Life Questionnaire (ACL-QOL), before and 16 weeks after the surgery.
      RESULTS: The functional outcomes in terms of the vertical jump test (p=0.012), a
      single hop-for-distance test (p=0.027), the Lysholm knee scale (p=0.002) and the
      ACL-QOL questionnaire (p=0.000) demonstrated significantly greater improvement in
      the study group. No significant difference was reported between groups for
      isokinetic strength of the knee extensors and flexors (p>0.05). CONCLUSION:
      Adding progressive eccentric and concentric exercises to the standard
      rehabilitation protocol may improve the functional results after ACL
      reconstruction with autogen hamstring grafts.

PMID- 24901919
TI  - Treatment of superior labrum anterior posterior lesions: a literature review.
AB  - OBJECTIVE: Treatment of superior labrum anterior posterior (SLAP) lesions
      continues to be controversial, but with the development of suture anchors, it has
      become acceptable to repair these lesions arthroscopically. The aim of this study
      was to review recent trends in the evaluation and treatment of SLAP lesions, with
      particular emphasis on comparing the results of biceps tenodesis and SLAP repair.
      METHODS: All English language publications from the PubMed, Cochrane, and SCOPUS
      databases between 1928 and 2012 on biceps tendon, SLAP lesions, and biceps
      surgery were reviewed. Literature was reviewed in table form because of the lack
      of Level 1 studies. RESULTS: Surgical repair can have complications and may not
      return overhead athletes to their previous level of activity. Biceps tenodesis
      has become the preferred primary procedure in non-athletic individuals because of
      the high failure rate of SLAP repair. In patients with continuing symptoms after
      SLAP lesion repair, biceps tenodesis offers a more predictable operation than a
      second repair attempt. CONCLUSION: Biceps tenodesis may present a viable
      treatment option for SLAP repair or for failed SLAP repair in some patients.

PMID- 24901920
TI  - Application of three-dimensional model in the management of irreducible atlanto
      axial dislocation.
AB  - OBJECTIVE: The aim of this study was to describe the application of the rapid
      prototyping (RP) life-size 3-dimensional model used to improve accuracy of screw
      insertion in irreducible atlanto-axial dislocation (IAD). METHODS: The study
      included 10 patients with IAD. All patients were assessed using the Japanese
      Orthopedic Association (JOA) score. Radiographs, MRI and CT were conducted during
      the preoperative and postoperative procedure. A 3D RP model was created for each
      patient. The model was used to obtain detailed information of each pedicle and
      used as an intraoperative reference. Assisted by the model, transoral atlanto
      axial reduction plate fixation was performed in each case. RESULTS: The average
      operation time was 145 (range: 90 to 180) minutes and average blood loss was 120
      (range: 60 to 250) ml. JOA scores improved after surgery. All 40 transoral
      pedicle/lateral mass screws were placed without serious complications or internal
      fixation failure. Postoperative radiographs and CT scan showed 38 transoral
      pedicle/lateral mass screws located in the pedicle tracts. Satisfactory reduction
      was achieved in 95% of screws. Two screws perforated the lateral wall of the C2
      pedicles in an extremely narrow pedicle case. No neurologic sequelae or vertebral
      artery injury were detected. CONCLUSION: The RP technique is effective and
      reliable in achieving an accurate and safe screw insertion during IAD surgery,
      especially in anatomically abnormal cases.

PMID- 24901921
TI  - The efficacy of cell saver method in the surgical treatment of adolescent
      idiopathic scoliosis.
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy of the
      intraoperative blood salvage cell saver method for allogeneic blood transfusion
      in the surgical treatment of adolescent idiopathic scoliosis with pedicle screw
      and rod combination. METHODS: The study included 33 patients (5 males and 28
      females) who underwent surgery due to adolescent idiopathic scoliosis. Patients
      were divided into 2 groups; 16 patients (mean age: 17.1+/-3.9 years) in Group A
      were operated using the cell saver (Medtronic Autolog; autologous cell saver
      machine) method and the 17 patients (mean age 18.7+/-6.8 years) in Group B
      (control group) were treated without cell saver. The Cobb angle, levels of
      pedicle fixation, operation time, postoperative bleeding, hemoglobin change,
      allogeneic blood replacement and the amount of autologous erythrocytes were
      recorded. RESULTS: Mean level of pedicle fixation was 12.9+/-1.54 vertebra using
      a mean of 21.1+/-3.21 screws in Group A and 12.8+/-1.47 vertebra using 18.7+/
      3.59 screws in Group B (p>005). The mean operation time was 224 (Group A: 228+/
      58; Group B: 221+/-60) minutes. There were no statistically significant
      differences in the demographic characteristics of both groups (p>0.05). The
      preoperative mean hemoglobin levels were 12.2+/-1.47 mg/dl in Group A and 13.1+/
      1.56 mg/dl in Group B. Postoperative mean hemoglobin level was 11.3+/-1.62 mg/dl
      in Group A and 9.86+/-0.93 mg/dl in Group B (p=0.004). The mean amount of
      autologous erythrocyte replacement was 284+/-139 ml. The mean postoperative
      bleeding was 834+/-253 ml in Group A and 759+/-380 ml in Group B (p>0.05). The
      mean allogeneic blood replacement was 1.88+/-0.88 units in Group A and 1.94+/
      1.34 in Group B (p>0.05). CONCLUSION: Autologous erythrocyte replacement was
      possible using the cell saver method. However, there was no decrement in
      allogeneic blood replacement using cell saver in the surgical treatment of
      adolescent idiopathic scoliosis.

PMID- 24901922
TI  - Intramedullary skeletal kinetic distractor in lower extremity lengthening.
AB  - OBJECTIVE: The aim of this study was to report the clinical and radiological
      results of patients with Intramedullary Skeletal Kinetic Distractor (ISKD)
      lengthening. METHODS: Ten femoral and 2 tibial lengthening were performed in 12
      patients (7 male, 5 female; mean age: 27 years (13-40)) by using ISKD nail. The
      mean limb length discrepancy of the patients was 4.41 cm (2-7). On the
      postoperative 7th day the patients were trained about lengthening and the
      lengthening started. Follow-up X rays were taken weekly during the distraction
      period and every second weeks during the consolidation period. One patient with
      tibia lengthening was lost to follow-up after completing the distraction period.
      RESULTS: The planned lengthening amounts were achieved in all of the cases. The
      mean lengthening was 4.41 cm (2-7). The mean bone healing index was 37.8 day/cm
      (28.5-78.0). There were uncontrolled distractions in 4 cases. Autogenous bone
      grafting was necessary in a case with incompetent bone formation. The kinetic
      nail was locked and failed to distract in a patient, in which the problem was
      solved with closed manipulation under anesthesia. No patient had a joint
      stiffness. CONCLUSION: Intramedullary extensible nails decrease the risk of joint
      contractures and infection. This procedure can be well tolerated by the patients
      and they can return to their daily activities earlier.

PMID- 24901923
TI  - Does insulin, transferrin and selenous acid preparation effect chondrocyte
      proliferation?
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that insulin, human
      transferrin, and selenous acid (ITS) preparation have positive effects on
      chondrocyte proliferation and morphology and investigate the biochemical and
      histological effects of these additive substances in different cell culture
      media. METHODS: Human cartilage-derived cells (hCDCs) were isolated from the
      cartilage tissue of a 57-year-old woman diagnosed with gonarthrosis. Tissue
      samples were cultured in Dulbecco's modified Eagle's medium (DMEM) and RPMI-1640.
      The cells' chondrogenic activities were observed. After serial passagings, cells
      were divided into 4 groups at the end of the 6th week. On the 14th day,
      proliferated cells were examined using an inverted microscope with x4, x10, x20
      and x40 magnification and microphotographs were taken. Living cell quantity was
      determined on the first and 14th days using MTS-ELISA cell proliferation assay.
      RESULTS: DMEM (without adding ITS premix solution) and RPMI-1640 containing ITS
      premix solution provide proliferation of the chondrogenic cells. The
      proliferation and viability of chondrocytes were revealed in this study in the
      3rd group (DMEM solution without additives). CONCLUSION: It is suggested that the
      culture medium ingredients play crucial roles on chondrogenic proliferation in
      osteochondral tissue cultures.

PMID- 24901925
TI  - Effects of bone drilling on local temperature and bone regeneration: an in vivo
      study.
AB  - OBJECTIVE: The aim of this study was to examine the influence of bone drilling on
      local bone temperature and bone regeneration and determine optimal drilling speed
      and pressure in an animal model. METHODS: The study included 12 skeletally mature
      New Zealand white rabbits, weighing between 2.8 to 3.2 kg. Rabbits were divided
      into 2 groups and euthanized at the end of Day 21 (Group A) and Day 42 (Group B).
      The same drilling protocol was used in both groups. Three drill holes with
      different pressure (5, 10 and 20 N) were made in each rabbit tibias using 3
      different rotational drill speeds (230, 370 and 570 rpm). During drilling, local
      temperature was recorded. Rabbit tibia underwent histopathological exam for bone
      regeneration. RESULTS: Bone temperature was affected by drilling time and depth.
      Lower drill speeds reduced the bone temperature and revealed better bone
      regeneration when compared to the drilled bones at higher drill speeds. Titanium
      boron nitride coating on the drill bits had no significant effects on bone
      temperature and structure. Bone regeneration was superior in Group B rabbits that
      had drilling at 230 rpm and 20 N. CONCLUSION: Our results suggested that lower
      drilling speed with higher pressure is necessary for better bone regeneration.
      The optimal drilling speed is 230 rpm and optimal drilling pressure 20 N.

PMID- 24901924
TI  - Histomorphological comparison of immobilization and denervation atrophies.
AB  - OBJECTIVE: The aim of this study was to compare the histomorphological changes in
      the muscle tissue after immobilization and denervation atrophies in an animal
      model. METHODS: The study included 30 Ross-800 hybrid chickens (60 legs) divided
      into two study (immobilization and denervation) and two control groups. The knee
      and ankle joints were fixed with a Kirschner wire in the immobilization atrophy
      group and sciatic nerve resection was performed in the denervation group. The
      unaffected side of each group was used as controls. The weight, volume, height,
      diameter and the rate of elongation of the Achilles tendons, and the amount of
      fat deposition, degeneration and fibrosis were compared between the two groups at
      the end of 3 weeks. Hematoxylin-eosin staining was performed for a
      histopathological assessment of the muscles. The Mann-Whitney U-test was used for
      comparisons. RESULTS: Loss of the volume, weight and muscle length was
      significantly lower in the denervation group than the immobilization group
      (p<0.05). Differences between the diameter of the Achilles tendon and length and
      diameter of the short heads were not statistically significant. There were
      statistically significant differences in fat deposition, degeneration and
      fibrosis between the degeneration group and the immobilization group (p<0.05).
      Pixel counting revealed a significant difference in the number of pixels in the
      fatty tissue area (white area) between the denervation group and the
      immobilization group (p<0.05). CONCLUSION: Our results showed that
      histomorphological changes were more in the denervation group than the
      immobilization group in an experimental chicken model.

PMID- 24901926
TI  - Investigation of mechanical strength of teicoplanin and ciprofloxacin impregnated
      bone cement on Day 1 and Day 15.
AB  - OBJECTIVE: The aim of this study was to compare the mechanical effects of
      different concentrations of teicoplanin and ciprofloxacin addition in bone
      cement. METHODS: In an experimental design, 3 different doses of teicoplanin and
      ciprofloxacin (800, 1600 and 3200 mg) were added to bone cement. Mechanical tests
      using compression and four-point bending tests were performed on Day 1 and after
      antibiotic leaching in water at 37 degrees C on Day 15. Specimens that contained
      no antibiotics served as controls. Mechanical strength for each antibiotic
      concentration on Day 1 and Day 15 were evaluated. RESULTS: Both teicoplanin and
      ciprofloxacin significantly decreased the mean strength values in compression and
      four-point bending tests at Days 1 and 15 (p<0.05). While teicoplanin
      significantly decreased the mean strength values at high doses in both tests at
      Days 1 and 15 (p<0.05), ciprofloxacin did not significantly change these values.
      When the effects of two drugs compared, there were significant differences at the
      3200 mg dose at Day 1 and at 1600 and 3200 mg doses at Day 15 in the compression
      testing and at 3200 mg at Day 15 in the four-point bending test. CONCLUSION:
      Teicoplanin and ciprofloxacin addition may adversely affect the biomechanical
      strength of bone cement. Ciprofloxacin addition seems to have less of a negative
      effect on strength than teicoplanin.

PMID- 24901928
TI  - The effect of organic silicon injection on Achilles tendon healing in rats.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of a soluble
      absorbable silicon compound on healing of the Achilles tendon. METHODS: The
      Achilles tendons of 21 Wistar albino rats were cut and repaired. A 0.01 ml
      organic silicon solution (silanol) was injected peri/intratendinously into the
      left leg of all rats and the same dose of saline into the right leg
      postoperatively. Rats were randomly divided into 3 groups for biomechanical
      testing on Day 10 (7 rats) and Day 20 (7 rats) and histological and
      immunohistochemical assessment on Day 20 (7 rats). Fibroblast cell count and
      diameter, tissue vascularity and blood vessel diameter were evaluated by
      histomorphometry. Basic fibroblast growth factor (bFGF) immunoreactivity was
      analyzed with immunohistochemistry on Day 20. Failure load and stiffness of the
      repaired tendons were measured on Days 10 and 20. RESULTS: The number of
      fibroblasts per area, average fibroblast diameter, number of vessels parallel to
      collagen bundles per area and average vessel diameter were significantly higher
      in the organic silicon group than in the control group (p<0.05). Strong
      immunoreactivity of bFGF in the silicon group was detected. Failure load was
      significantly higher in the silicon group than in the control group on Day 10
      (p=0.041). On Day 20, while a difference still existed, this difference was not
      significant. There was no effect of the silicon injection on stiffness of healing
      tendons. CONCLUSION: Organic silicon appears to have a positive effect on tendon
      healing and is suitable for further studies on host healing response
      modification.

PMID- 24901927
TI  - The effects of melatonin and caffeic acid phenethyl ester (CAPE) on fracture
      healing under ischemic conditions.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of antioxidant
      molecules melatonin and caffeic acid phenethyl ester (CAPE) on fracture healing
      under ischemic conditions. METHODS: A right tibia fracture was created and fixed
      with an intramedullary pin in forty four male Wistar-albino rats. The rats were
      then randomly allocated to fracture, fracture-ischemia, fracture- ischemia
      melatonin, and fracture-ischemia-CAPE groups. Ischemia was created by clamping
      femoral arteries four and a half hours. Animals were killed and radiographic,
      histological and biomechanical evaluation was performed sixth week after surgery.
      RESULTS: The radiological and histological scores of the fracture-ischemia-CAPE
      group were significantly better than the fracture- ischemia group at 6th week
      follow-up. Complete radiographical and histological healing of all fractures was
      detected in all groups. There was a significant difference between the maximum
      fracture force between the groups (fracture-ischemia<fracture-ischemia
      melatonin<fracture<fracture-ischemia-CAPE) (p<0.005). Although difference was not
      statistically significant between fracture and fracture-ischemia-CAPE groups, all
      other groups revealed statistically significant difference with respect to
      toughness (N/mm). Fracture-ischemia group revealed the lowest toughness.
      CONCLUSION: Ischemia adversely affects the fracture healing of rat tibias.
      Melatonin and CAPE eradicate adverse effects of ischemia. Possible adverse
      effects of ischemia on fracture healing can be eradicated with melatonin and CAPE
      in patients with tibia fractures associated with vascular injury or compartment
      syndrome.

PMID- 24901929
TI  - The effects of resveratrol on tendon healing of diabetic rats.
AB  - OBJECTIVE: The aim of this study was to determine the effects of resveratrol on
      the tendon healing process of streptozotocin-induced diabetic rats. METHODS: The
      study included 16 male Sprague-Dawley rats. Streptozotocin was administered to
      induce diabetes and bilateral tenorrhaphy of the Achilles tendons was performed.
      Intraperitoneal resveratrol was injected in the experimental group (n=8) and
      saline in the control group (n=8) during the postoperative period. Rats were
      sacrificed at the 14th day. Right side tendons were evaluated biomechanically and
      left side tendons histologically. RESULTS: Difference in mean tendon tensile
      strength was not statistically significant between groups (p>0.05). Histologic
      evaluations of the repair zones showed greater configuration of the newly
      synthesized collagen in the experimental group. The ratio of the newly
      synthesized collagen area to the healing region area was significantly higher in
      the experimental group then the control group (p<0.01). CONCLUSION: Resveratrol
      appears to have a positive impact on the process of tendon healing in diabetic
      conditions in the first 14 days.

PMID- 24901930
TI  - Irreducible fracture-dislocation of the knee.
AB  - Dislocation and fracture-dislocation of the knee are serious injuries, often
      related to high-energy trauma. Irreducibility with closed techniques is an
      extremely rare and challenging problem that has been described in posterolateral,
      posterior and lateral knee dislocations. Irreducibility in fracture-dislocations
      around the knee has only been described twice in the literature and never in
      association with a tibial plateau fracture. We report a unique case of an
      irreducible tibial plateau fracture-dislocation in which closed reduction was
      prevented by incarceration of the medial meniscus within the fracture site. The
      patient required transfer to our institution due to a concomitant traumatic brain
      injury. This contributed to a delay of 10 hours from injury to arrival in our
      resuscitation room. Progressive swelling and absent foot pulses resulted in
      immediate transfer to the operating theater where open reduction and internal
      fixation was performed with four-compartmental fasciotomies. The patient made a
      rapid and full recovery. Where closed techniques have failed, open reduction must
      then be undertaken in order to prevent the devastating complications of
      compartment syndrome and neurovascular compromise. 

PMID- 24901931
TI  - Patellar ligament rupture during total knee arthroplasty in an ochronotic
      patient.
AB  - Ochronotic arthropathy mainly involves the spine and large joints. Along with
      blackening of the joint, degeneration rapidly progresses mostly in the knee,
      resulting in symptoms by the 4th or 5th decade. As the role of medical treatment
      and joint conservation surgeries are limited in the early stages, joint
      replacement is the only effective option in one third of patients. We present a
      case of the unique complication of patellar ligament rupture during total knee
      replacement (TKR) of an ochronotic joint. A 51-year-old male presented with
      bilateral severe tricompartmental osteoarthritis with varus deformities and
      restriction of motion. Bilateral TKR was performed. At the 28-month follow-up,
      the patient was walking pain free with acceptable position of implants in
      radiographs. To our knowledge this is the first report of rupture of the patellar
      ligament during TKR of an ochronotic joint. We propose appropriate preoperative
      preparation and greater care in the handling of the tendon during TKR of an
      ochronotic joint in order to avoid complication. 

PMID- 24901932
TI  - Evaluation of primary bone lymphoma and the importance of positron emission
      tomography.
AB  - Primary lymphoma of the bone is an extremely rare tumor in the form of non
      Hodgkin lymphoma or Hodgkin lymphoma. The majority of primary bone lymphomas are
      non-Hodgkin lymphoma, of which the most common subtype is diffuse large cell
      lymphoma. Patients can present with pain, swelling or pathologic fracture.
      Definitive diagnosis is made after biopsy examination. Treatment consists of
      chemotherapy, radiotherapy and surgery. We report 3 male patients who presented
      with pain and swelling. Involvement was in the distal femur, proximal fibula and
      iliac crest in all patients. Patients were diagnosed with non-Hodgkin lymphoma in
      biopsy examination and underwent chemotherapy. The patient with distal femoral
      involvement underwent distal femoral resection prosthesis. Another patient with
      involvement of the fibular head experienced foot drop and delayed wound healing.
      Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography
      revealed complete response to the treatment. Patients are in remission and
      continue schooling. 

PMID- 24901933
TI  - A rare cartilaginous tumor in the phalangeal bone: enchondroma protuberans.
AB  - Enchondroma protuberans is a very rare benign cartilage tumor. Unlike
      intramedullary enchondromas; they originate from medulla and expands
      exophytically outside the cortex. We presenet a 19-year-old male patient with an
      enchondroma protuberans treated surgically, with excision and intramedullary
      curettage. The patient was asymptomatic and no recurrence was recorded in the 1
      year follow-up. 

PMID- 24901935
TI  - A normative theory of forgetting: lessons from the fruit fly.
AB  - Recent experiments revealed that the fruit fly Drosophila melanogaster has a
      dedicated mechanism for forgetting: blocking the G-protein Rac leads to slower
      and activating Rac to faster forgetting. This active form of forgetting lacks a
      satisfactory functional explanation. We investigated optimal decision making for
      an agent adapting to a stochastic environment where a stimulus may switch between
      being indicative of reward or punishment. Like Drosophila, an optimal agent shows
      forgetting with a rate that is linked to the time scale of changes in the
      environment. Moreover, to reduce the odds of missing future reward, an optimal
      agent may trade the risk of immediate pain for information gain and thus forget
      faster after aversive conditioning. A simple neuronal network reproduces these
      features. Our theory shows that forgetting in Drosophila appears as an optimal
      adaptive behavior in a changing environment. This is in line with the view that
      forgetting is adaptive rather than a consequence of limitations of the memory
      system. 

PMID- 24901936
TI  - Unavoidable pressure injury: state of the science and consensus outcomes.
AB  - In the vast majority of cases, appropriate identification and mitigation of risk
      factors can prevent or minimize pressure ulcer (PU) formation. However, some PUs
      are unavoidable. Based on the importance of this topic and the lack of literature
      focused on PU unavoidability, the National Pressure Ulcer Advisory Panel hosted a
      multidisciplinary conference in 2014 to explore the issue of PU unavoidability
      within an organ system framework, which considered the complexities of
      nonmodifiable intrinsic and extrinsic risk factors. Prior to the conference, an
      extensive literature review was conducted to analyze and summarize the state of
      the science in the area of unavoidable PU development and items were developed.
      An interactive process was used to gain consensus based on these items among
      stakeholders of various organizations and audience members. Consensus was reached
      when 80% agreement was obtained. The group reached consensus that unavoidable PUs
      do occur. Consensus was also obtained in areas related to cardiopulmonary status,
      hemodynamic stability, impact of head-of-bed elevation, septic shock, body edema,
      burns, immobility, medical devices, spinal cord injury, terminal illness, and
      nutrition.

PMID- 24901937
TI  - A day in the life of fish larvae: modeling foraging and growth using quirks.
AB  - This article introduces "Quirks," a generic, individual-based model synthesizing
      over 40 years of empirical and theoretical insights into the foraging behavior
      and growth physiology of marine fish larvae. In Quirks, different types of larvae
      are defined by a short list of their biological traits, and all foraging and
      growth processes (including the effects of key environmental factors) are modeled
      following one unified set of mechanistic rules. This approach facilitates
      ecologically meaningful comparisons between different species and environments.
      We applied Quirks to model young exogenously feeding larvae of four species: 5.5
      mm European anchovy (Engraulis encrasicolus), 7-mm Atlantic cod (Gadus morhua),
      13-mm Atlantic herring (Clupea harengus), and 7-mm European sprat (Sprattus
      sprattus). Modeled growth estimates explained the majority of variability among
      53 published empirical growth estimates, and displayed very little bias: 0.65% +/
      1.2% d(-1) (mean +/- standard error). Prey organisms of ~ 67% the maximum
      ingestible prey length were optimal for all larval types, in terms of the
      expected ingestion per encounter. Nevertheless, the foraging rate integrated over
      all favorable prey sizes was highest when smaller organisms made up >95% of the
      prey biomass under the assumption of constant normalized size spectrum slopes.
      The overall effect of turbulence was consistently negative, because its
      detrimental influence on prey pursuit success exceeded its beneficial influence
      on prey encounter rate. Model sensitivity to endogenous traits and exogenous
      environmental factors was measured and is discussed in depth. Quirks is free
      software and open source code is provided.

PMID- 24901938
TI  - The ubiquitin-conjugating enzyme, UbcM2, is restricted to monoubiquitylation by a
      two-fold mechanism that involves backside residues of E2 and Lys48 of ubiquitin.
AB  - Proteins can be modified on lysines (K) with a single ubiquitin (Ub) or with
      polymers of Ub (polyUb). These different configurations and their respective
      topologies are primary factors for determining whether substrates are targeted to
      the proteasome for degradation or directed to nonproteolytic outcomes. We report
      here on the intrinsic ubiquitylation properties of UbcM2 (UBE2E3/UbcH9), a
      conserved Ub-conjugating enzyme linked to cell proliferation, development, and
      the cellular antioxidant defense system. Using a fully recombinant ubiquitylation
      assay, we show that UbcM2 is severely limited in its ability to synthesize polyUb
      chains with wild-type Ub. Restriction to monoubiquitylation is governed by
      multiple residues on the backside of the enzyme, far removed from its active
      site, and by lysine 48 of Ub. UbcM2 with mutated backside residues can synthesize
      K63-linked polyUb chains and to a lesser extent K6- and K48-linked chains.
      Additionally, we identified a single residue on the backside of the enzyme that
      promotes monoubiquitylation. Together, these findings reveal that a combination
      of noncatalytic residues within the Ubc catalytic core domain of UbcM2 as well as
      a lysine(s) within Ub can relegate a Ub-conjugating enzyme to monoubiquitylate
      its cognate targets despite having the latent capacity to construct polyUb
      chains. The two-fold mechanism for restricting activity to monoubiquitylation
      provides added insurance that UbcM2 will not build polyUb chains on its
      substrates, even under conditions of high local Ub concentrations. 

PMID- 24901940
TI  - High-flux oxygen-transporting membrane Pr(0.6)Sr(0.4)Co(0.5)Fe(0.5)O(3-delta):
      CO2 stability and microstructure.
AB  - High oxygen permeability and good thermochemical stability of oxygen-transporting
      membranes (OTMs) are two main requirements concerning the applicability of these
      devices in chemical processes, such as CO2 capture using the oxyfuel concept or
      catalytic membrane reactors. In this work, a single-phase perovskite-type
      membrane Pr0.6Sr0.4Co0.5Fe0.5O3-delta (PSCF) with 0.6-mm thickness was subjected
      to periodic thermal cycling in the temperature range between 850 and 1000 
      degrees C in a 1000-h long-term permeation test with pure CO2 as the sweep gas.
      The results of this long-term permeation operation revealed a stepwise increase
      in oxygen permeation values at 1000  degrees C after each thermal cycle, reaching
      from 1.38 cm(3) (STP) min(-1) cm(-2) in the first cycle to 1.75 cm(3) (STP) min(
      1) cm(-2) in the fourth cycle. Furthermore, the membrane showed very good CO2
      stability at 900  degrees C and above. Despite a partial decrease in oxygen
      permeation fluxes at 850  degrees C, a steady state of 0.25 cm(3) (STP) min(-1)
      cm(-2) was reached and maintained for more than 100 h. The newly developed PSCF
      membrane also exhibited a higher oxygen permeation flux with He and CO2 sweeping
      at all measured temperatures compared to a similar La0.6Sr0.4Co0.8Fe0.2O3-delta
      (LSCF) membrane. 

PMID- 24901939
TI  - Wet season upwelling and dry season chlorophyll-a describe interannual growth
      rates of Porites in southern China.
AB  - Southern China hosts coral communities in marginal environments that are
      characterized by low linear extension rates, low coral cover and/or no reef
      formation, thus providing natural laboratories to study coral communities with
      below average growth rates. Here we compare the annual linear extension rates
      over 10 years (range 1.2 to 11.4 mm yr-1) of six Porites sp. coral cores
      collected from Hong Kong with monthly hydrographic data from the Hong Kong
      Environmental Protection Department. At all sites, low-density, dry season
      extension were more variable than high-density, wet season extension and on
      average, was lower at two of the three sites. We applied multi-variate linear
      regressions that revealed high-density, wet season band extension to inversely
      correlate most significantly to temperature (r = -0.39, p<0.01). In contrast, low
      density, dry season band extension was more variable and correlated most
      significantly with dry season chlorophyll-a (Chl-a) (r = 0.64, p<0.001).
      Additionally, we find that corals at the site with highest dry season Chl-a have
      the highest dry season extension lengths. Our findings indicate that relative
      mixing of fresh and salt water in the wet season and primary productivity in the
      dry season, and their influences on aragonite saturation, are likely to impact
      interannual coral extension variability in marginal environments. 

PMID- 24901941
TI  - Targeting genetic lesions in esophageal cancer.

PMID- 24901942
TI  - Hyperendemic Chagas disease and the unmet need for pacemakers in the Bolivian
      Chaco.

PMID- 24901944
TI  - Selective oxidation of alcohols with alkali metal bromides as bromide catalysts:
      experimental study of the reaction mechanism.
AB  - A bromide-catalyzed oxidation of alcohols was developed which proceeded in the
      presence of an alkali metal bromide and an oxidant under mild conditions. The
      reaction involved an organic-molecule-free oxidation using KBr and Oxone and a
      Bronsted acid assisted oxidation using KBr and aqueous H2O2 solution to provide a
      broad range of carbonyl compounds in high yields. Moreover, the bromide-catalyzed
      oxidation of primary alcohols enabled the divergent synthesis of carboxylic acids
      and aldehydes under both reaction conditions in the presence of TEMPO. A possible
      catalytic mechanism was suggested on the basis of various mechanistic studies. 

PMID- 24901943
TI  - Association between low serum magnesium level and major adverse cardiac events in
      patients treated with drug-eluting stents for acute myocardial infarction.
AB  - OBJECTIVES: We investigated the association of serum magnesium (Mg) levels and
      major adverse cardiac events (MACEs) after drug-eluting stent (DES) implantation.
      BACKGROUND: Mg depletion plays a key role in the pathphysiologic features of
      diabetes mellitus, hypertension, thrombosis, arrhythmias and coronary artery
      disease. Whether the depletion is related to the long-term prognosis of DES
      implantation is not known. METHODS: From 2008 to 2011, we enrolled 414
      consecutive patients <50 years old who underwent DES implantation for acute
      coronary syndrome. Serum Mg level was analyzed and patients were followed up for
      a median of 24 months (interquartile range 14-32 months) for the occurrence of
      MACEs defined as death, myocardial infarction, stroke, and any revascularization.
      RESULTS: For patients with unstable angina, no significant association between
      serum Mg level and MACEs was found in the multivariate model. For patients with
      myocardial infarction, after adjusting for age, positive family history, smoking
      status, hypertension, hypercholesterolemia, and diabetes at baseline, the risk
      was 8.11-fold higher for patients with quartile 1 than 4 Mg level (95% confidence
      interval 1.7-38.75; P<0.01). In addition, when tested as a continuous variable,
      serum magnesium was a significant predictor for MACEs of acute myocardial
      infarction (HR [per 0.1 mM increase], 0.35 [95% CI, 0.19-0.63], p< 0.01), after
      adjustment for other confounders. CONCLUSIONS: Low serum level of Mg may be an
      important predictor of MACEs with DES implantation for acute myocardial
      infarction. Further research into the effectiveness of Mg supplementation for
      these patients is warranted.

PMID- 24901945
TI  - Memory decline in Down syndrome and its relationship to iPF2alpha, a urinary
      marker of oxidative stress.
AB  - BACKGROUND: Lipid peroxidation may be a marker of free-radical-mediated injury
      associated with Alzheimer's disease (AD). We aimed to investigate whether changes
      in lipid peroxidation is associated with cognitive decline in individuals with
      Down syndrome over a 4-year period. METHODS: Thirty-two adults with DS
      participated in a longitudinal study with urinary isoprostane 8,12-iso-iPF2alpha
      (iPF2alpha) assays at baseline and four years follow-up. Informants rated their
      functional ability and memory function and the adults with DS attempted
      assessments of language skills and memory. Twenty-six individuals completed
      assessments of memory (Modified Memory Object Task, MOMT), adaptive behavior
      (ABAS), and receptive vocabulary (British Picture vocabulary, BPVS) at both time
      points. RESULTS: Overall change in iPF2alpha level was negatively correlated with
      change in the MOMT score (Spearman's Rho =  -0.576, p = 0.006), i.e., increased
      lipid peroxidation was correlated with worse memory functioning over time. An
      increase of >= 0.02 ng/mg creatinine iPF2alpha had good sensitivity (85.7%),
      positive predictive value (75%,), specificity (85.7%) and negative predictive
      value (92.3%) for memory decline. CONCLUSION: Change in iPF2alpha over time may
      have potential as a biomarker for memory decline in Down syndrome and potentially
      also help to track progression of MCI to AD in the general population.

PMID- 24901947
TI  - Oil-in-water microemulsion droplets of TDMAO/decane interconnected by the
      telechelic C18-EO150-C18: clustering and network formation.
AB  - The effect of a doubly hydrophobically end-capped water soluble polymer (C18
      PEO150-C18) on the properties of an oil-in-water (O/W) droplet microemulsion (R ~
      2.85 nm) has been studied as a function of the amount of added telechelic
      polymer. Macroscopically one observes a substantial increase of viscosity once a
      concentration of ~5 hydrophobic stickers per droplet is surpassed and effective
      cross-linking of the droplets takes place. SANS measurements show that the size
      of the individual droplets is not affected by the polymer addition but it induces
      attractive interactions at low concentration and repulsive ones at high polymer
      content. Measurements of the diffusion coefficient by DLS and FCS show increasing
      sizes at low polymer addition that can be attributed to the formation of clusters
      of microemulsion droplets interconnected by the polymer. At higher polymer
      content the network formation leads to an additional slow relaxation mode in DLS
      that can be related to the rheological behaviour, while the self-diffusion
      observed in FCS attains a lower plateau value, i.e., the microemulsion droplets
      remain effectively fixed within the network. The combination of SANS, DLS, and
      FCS allows us to derive a self-consistent picture of the evolution of structure
      and dynamics of the mixed system microemulsion/telechelic polymer as a function
      of the polymer content, which is not only relevant for controlling the
      macroscopic rheological properties but also with respect to the internal dynamics
      as it is, for instance, relevant for the release and transport of active agents. 

PMID- 24901946
TI  - Surveillance of influenza viruses in waterfowl used as decoys in Andalusia,
      Spain.
AB  - A longitudinal study was carried out to determine the seroprevalence of avian
      influenza viruses (AIVs) in waterfowl used as decoys in Andalusia, southern
      Spain. A total of 2319 aquatic birds from 193 flocks were analyzed before and
      after the hunting season 2011-2012. In the first sampling, 403 out of 2319
      (18.0%, CI95%: 15.8-19.0) decoys showed antibodies against AIVs by ELISA. The AI
      seroprevalence was significantly higher in geese (21.0%) than in ducks (11.7%)
      (P<0.001). Besides, the spatial distribution of AIVs was not homogeneous as
      significant differences among regions were observed. The prevalence of antibodies
      against AIVs subtypes H5 and H7 were 1.1% and 0.3%, respectively, using
      hemagglutination inhibition test (HI). The overall and H5 seroprevalences
      slightly increased after the hunting period (to 19.2% and 1.4%, respectively),
      while the H7 seroprevalence remained at the same level (0.3%). The proportion of
      flocks infected by AIVs was 65.3%, while 11.2% and 4.9% of flocks were positive
      for H5 and H7, respectively. Viral shedding was not detected in any of the 47
      samples positive by both ELISA and HI, tested by RRT-PCR. The individual
      incidence after the hunting season was 3.4%. The fact that 57 animals
      seroconverted, 15 of which were confirmed by HI (12 H5 and 3 H7), was indication
      of contact with AIVs during the hunting period. The results indicate that
      waterfowl used as decoys are frequently exposed to AIVs and may be potentially
      useful as sentinels for AIVs monitoring. The seroprevalence detected and the
      seropositivity against AIVs H5 and H7, suggest that decoys can act as reservoirs
      of AIVs, which may be of animal and public health concern.

PMID- 24901948
TI  - Evaluation of anti-inflammatory activity of prenylated substances isolated from
      Morus alba and Morus nigra.
AB  - Chromatographic separation of root extracts of Morus alba and M. nigra led to the
      identification of the 2-arylbenzofurans moracin C (1), mulberrofuran Y (2), and
      mulberrofuran H (3), and the prenylated flavonoids kuwanon E (4), kuwanon C (5),
      sanggenon H (6), cudraflavone B (7), and morusinol (8), and the Diels-Alder
      adducts soroceal (9), and sanggenon E (10). The cytotoxicity and their
      antiphlogistic activity, determined as the attenuation of the secretion of TNF
      alpha and IL-1beta and the inhibition of NF-kappaB nuclear translocation in LPS
      stimulated macrophages, were evaluated for compounds 1-10. 

PMID- 24901950
TI  - Comparison of electrocardiographic characteristics of adults and children for
      automated external defibrillator algorithms.
AB  - Accurate rhythm identification is vital for appropriate shock delivery during
      pediatric resuscitation with an automated external defibrillator. Currently,
      extensive testing of pediatric algorithms is recommended. The aims of our study
      were to determine age-related differences in electrocardiographic (ECG) tracings
      in children and adults and to determine if differences warrant evaluating each
      algorithm against pediatric rhythms. We hypothesized that the ECG characteristics
      of heart rate, amplitude, and conduction velocity differ between children younger
      than 8 years and adults. We evaluated 442 separate ECG tracings from 199
      pediatric patients and 839 samples from 170 adults to measure differences in the
      3 variables. Rhythms chosen were normal sinus rhythm (NSR), supraventricular
      tachycardia (SVT), and ventricular tachycardia (VT). Significant differences were
      found between heart rates of children and adults with NSR and SVT but not VT.
      There were significant differences between adult and pediatric signal amplitudes
      in both NSR and SVT but no difference in signal amplitude of VT. When NSR between
      adults and children was compared, adults proved to have a faster conduction
      velocity. There was no difference in conduction velocity of SVT or VT between
      children and adults. We conclude that common rhythms in pediatric patients have
      differing characteristics, which may affect the accuracy of an automated external
      defibrillator algorithm, and that specific testing with tracings obtained from
      children is warranted. 

PMID- 24901949
TI  - Efficient transient transfection of human multiple myeloma cells by
      electroporation--an appraisal.
AB  - Cell lines represent the everyday workhorses for in vitro research on multiple
      myeloma (MM) and are regularly employed in all aspects of molecular and
      pharmacological investigations. Although loss-of-function studies using RNA
      interference in MM cell lines depend on successful knockdown, no well-established
      and widely applied protocol for efficient transient transfection has so far
      emerged. Here, we provide an appraisal of electroporation as a means to introduce
      either short-hairpin RNA expression vectors or synthesised siRNAs into MM cells.
      We found that electroporation using siRNAs was much more efficient than
      previously anticipated on the basis of transfection efficiencies deduced from
      EGFP-expression off protein expression vectors. Such knowledge can even
      confidently be exploited in "hard-to-transfect" MM cell lines to generate large
      numbers of transient knockdown phenotype MM cells. In addition, special attention
      was given to developing a protocol that provides easy implementation, good
      reproducibility and manageable experimental costs. 

PMID- 24901951
TI  - Innovative Application of Cerebral rSO2 Monitoring During Shunt Tap in Pediatric
      Ventricular Malfunctioning Shunts.
AB  - OBJECTIVE: This study aimed to determine the reliability and potential
      application of cerebral regional tissue oxygenation (rSO2) monitoring in
      malfunctioning ventricular shunts during tap. METHODS: This is a prospective case
      series using convenience sample in subjects with confirmed malfunctioning shunt
      who had left and right cerebral rSO2 monitoring every 5 seconds before, during,
      and 1 hour after shunt tap. RESULTS: Ninety-four subjects had cerebral rSO2
      monitoring. Sixty-three subjects had proximal malfunctions, and 31 subjects had
      distal shunt malfunctions. The intrasubject's cerebral rSO2 trend and variability
      at pretap, during, and posttap times were highly correlated. Overall, the average
      rSO2 is lower in pretap as compared with posttap. Left cerebral rSO2 had lower
      means and larger SD as compared with right cerebral rSO2. Left pretap and posttap
      cerebral rSO2 variability was significantly associated with the location of shunt
      malfunction regardless of pretap, during, or posttap periods (P < 0.001), whereas
      right rSO2 variability was not predictive for malfunction location. Left cerebral
      rSO2 variability showed utility for identifying the location of malfunction with
      area under the receiver operating characteristic curve equal to 0.8. CONCLUSIONS:
      Reliable cerebral rSO2 readings before, during, and after shunt tap were
      demonstrated. Left cerebral rSO2 changes from before to after shunt tap were more
      predictive for shunt malfunction location than right cerebral rSO2 changes.
      Observing cerebral rSO2 changes in relationship to shunt tap represents a
      potential surrogate in measuring cerebral pressures and blood flow changes after
      cerebral spinal fluid drainage. Significantly greater cerebral rSO2 changes occur
      for distal malfunction versus proximal malfunction after shunt tap, indicating
      its potential as an adjunct tool for detecting shunt malfunction type.

PMID- 24901952
TI  - Visual-evoked potentials in patients with brain circulatory problems.
AB  - PURPOSE: The aim of this study was to find out if local brain circulatory
      problems may influence visual-evoked potentials (VEP). PATIENTS AND METHODS:
      Thirty-eight patients were divided into the following groups: (I) those with
      hemianopsia or quadrantanopsia and hemiparesis after brain stroke; (II) those
      with hemianopsia or quadrantanopsia without paresis after brain stroke; and (III)
      those with amaurosis fugax. The control group consisted of 38 patients. The VEP
      pattern (PVEP) and flash VEP (FVEP) were examined monocularly using two
      electrodes placed at O1 and O2. Latency and amplitude of the N75, P100 and N2, P2
      waves were measured. The Newman-Keuls test was used for statistical analysis.
      RESULTS: In PVEP, no differences between the groups were observed. In FVEP, the
      mean P2 latency was significantly longer in group I than in group III, and the P2
      amplitude was significantly lower in all examined groups when compared with the
      control group. PVEP and FVEP revealed differences in P latency over 3 ms between
      brain hemispheres and differences in P amplitude over 30% in all examined groups.
      In the control group, there were no differences in latency between brain
      hemispheres and only a small difference in amplitude. CONCLUSION: Local brain
      circulatory problems that may lead to brain ischemia cause differences in VEP
      amplitude and latency between brain hemispheres. Changes in VEPs observed in
      patients with amaurosis fugax may be considered the result of recurrent brain
      ischemia.

PMID- 24901953
TI  - A new method for evaluation of motor injury after acute brain ischemic damage.
AB  - PURPOSE: Motor impairment is an important index for assessing the extent of brain
      injury. The present study uses a new method, the movement capture analysis (MOCA)
      system, for assessing motor damage after acute ischemia. MATERIALS AND METHODS:
      Forty rats were divided into four groups: standard ischemia, sham-operated,
      Dizocilpine (MK-801), and Ginkgo biloba extract (GBE) groups. Brain ischemia was
      induced using the temporary right middle cerebral artery occlusion model. Longa
      score and MOCA were used to assess motor injury one day after ischemia. Infarct
      volume was delineated with 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining.
      The correlation of infarct volume with Longa score and MOCA data was calculated.
      RESULTS: Compared with the sham-operated group (0.10 +/- 0.31), Longa scores of
      MK-801 (2.33 +/- 0.73), GBE (1.80 +/- 0.58), and standard (2.88 +/- 0.83) groups
      showed a statistical difference (p < 0.05); however, it was unable to discern the
      difference between MK-801 and standard groups. MOCA was able to clearly discern
      the differences in motor disparity among the four groups, standard (1.00 +/-
      0.19), sham-operated group (0.17 +/- 0.02), MK-801 (0.79 +/- 0.08), GBE (0.38 +/-
      0.05) (p < 0.05). Both MK-801 (18.03 +/- 0.96%) and GBE (10.82 +/- 1.93%)
      treatment reduced infarct size compared with the standard ischemia group (25.88
      +/- 1.16%) (p < 0.05). The MOCA data showed a more significant correlation with
      infarct size than Longa score (r = 0.85:0.53). CONCLUSIONS: MOCA system proved to
      be more sensitive than the Longa score. It may potentially be more accurate
      method for behavioral evaluation in clinical trials.

PMID- 24901954
TI  - Conserving tropical tree diversity and forest structure: the value of small
      rainforest patches in moderately-managed landscapes.
AB  - Rainforests are undergoing severe deforestation and fragmentation worldwide. A
      huge amount of small forest patches are being created, but their value in
      conserving biodiversity and forest structure is still controversial. Here, we
      demonstrate that in a species-rich and moderately-managed Mexican tropical
      landscape small rainforest patches (<100 ha) can be highly valuable for the
      conservation of tree diversity and forest structure. These patches showed diverse
      communities of native plants, including endangered species, and a new record for
      the country. Although the number of logged trees increased in smaller patches,
      patch size was a poor indicator of basal area, stem density, number of species,
      genera and families, and community evenness. Cumulative species-area curves
      indicated that all patches had a similar contribution to the regional species
      diversity. This idea also was supported by the fact that patches strongly
      differed in floristic composition (high beta-diversity), independently of patch
      size. Thus, in agreement with the land-sharing approach, our findings support
      that small forest patches in moderately-managed landscapes should be included in
      conservation initiatives to maintain landscape heterogeneity, species diversity,
      and ecosystem services. 

PMID- 24901955
TI  - Cr(VI) adsorption and reduction by humic acid coated on magnetite.
AB  - Easily separable humic acid coated magnetite (HA-Fe3O4) nanoparticles are
      employed for effective adsorption and reduction of toxic Cr(VI) to nontoxic
      Cr(III). The adsorption and reduction of Cr(VI) is effective under acidic,
      neutral, and basic pH conditions. The chromium adsorption nicely fits the
      Langmuir isotherm model, and the removal of Cr(VI) from aqueous media by HA-Fe3O4
      particles follows pseudo-second-order kinetics. Characterization of the Cr-loaded
      HA-Fe3O4 materials by X-ray absorption near edge structure spectroscopy (XANES)
      indicates Cr(VI) was reduced to Cr(III) while the valence state of the iron core
      is unchanged. Fe K-edge extended X-ray absorption fine structure spectroscopy
      (EXAFS) and X-ray diffraction measurements also indicate no detectable
      transformation of the Fe3O4 core occurs during Cr(VI) adsorption and reduction.
      Thus, suggesting HA on the surface of HA-Fe3O4 is responsible for the reduction
      of Cr(VI) to Cr(III). The functional groups associated with HA act as ligands
      leading to the Cr(III) complex via a coupled reduction-complexation mechanism. Cr
      K-edge EXAFS demonstrates the Cr(III) in the Cr-loaded HA-Fe3O4 materials has six
      neighboring oxygen atoms likely in an octahedral geometry with average bond
      lengths of 1.98 A. These results demonstrate that easily separable HA-Fe3O4
      particles have promising potential for removal and detoxification of Cr(VI) in
      aqueous media. 

PMID- 24901957
TI  - Assessing solvent derivatization and carbon dioxide supercritical fluid
      simultaneous extraction/derivatization of cyprodinil.
AB  - Derivatization of cyprodinil with different reagents and solvents has been
      evaluated to improve the GC/MS characterization of this fungicide. After
      assessing some preliminary acylation and silylation reactions, derivatization
      with anhydrous heptafluorobutyric anhydride (HFBA) was selected as the best
      derivatization option for cyprodinil. The HFBA-cyprodinil derivative was clearly
      identified and characterized by GC/MS (ion-trap). The spectrum of the HFBA
      derivative of cyprodinil was characterized by the base peak, 252 m/z ion, and two
      other ions with relative abundances of 5% (224 m/z ion) and 4% (420 m/z molecular
      ion). Conversion rates in the range of 83-92% were obtained when 0.1-1 MUg
      cyprodinil were derivatized in vial without solvent at 25oC temperature for 120
      min, with 5 MUL HFBA and 5 MUL pyridine. Simultaneous extraction-derivatization
      of cyprodinil in supercritical carbon dioxide was only achieved when no modifier
      was present, but conversion/recovery rates obtained in the replicate experiments
      carried out with 15 mL supercritical carbon dioxide at 50 degrees C and 200 atm
      (n = 5), 300 atm (n = 7), and 400 atm (n = 5) were no reproducible (RSD > 50%)
      and ranged between 10% and 45% (related to the signal obtained for derivatization
      in vial).

PMID- 24901956
TI  - The UPBEAT nurse-delivered personalized care intervention for people with
      coronary heart disease who report current chest pain and depression: a randomised
      controlled pilot study.
AB  - BACKGROUND: Depression is common in people with coronary heart disease (CHD) and
      associated with worse outcome. This study explored the acceptability and
      feasibility of procedures for a trial and for an intervention, including its
      potential costs, to inform a definitive randomized controlled trial (RCT) of a
      nurse-led personalised care intervention for primary care CHD patients with
      current chest pain and probable depression. METHODS: Multi-centre, outcome
      assessor-blinded, randomized parallel group study. CHD patients reporting chest
      pain and scoring 8 or more on the HADS were randomized to personalized care (PC)
      or treatment as usual (TAU) for 6 months and followed for 1 year. Primary outcome
      was acceptability and feasibility of procedures; secondary outcomes included
      mood, chest pain, functional status, well being and psychological process
      variables. RESULT: 1001 people from 17 General Practice CHD registers in South
      London consented to be contacted; out of 126 who were potentially eligible, 81
      (35% female, mean age = 65 SD11 years) were randomized. PC participants (n = 41)
      identified wide ranging problems to work on with nurse-case managers. Good
      acceptability and feasibility was indicated by low attrition (9%), high
      engagement and minimal nurse time used (mean/SD = 78/19 mins assessment, 125/91
      mins telephone follow up). Both groups improved on all outcomes. The largest
      between group difference was in the proportion no longer reporting chest pain (PC
      37% vs TAU 18%; mixed effects model OR 2.21 95% CI 0.69, 7.03). Some evidence was
      seen that self efficacy (mean scale increase of 2.5 vs 0.9) and illness
      perceptions (mean scale increase of 7.8 vs 2.5) had improved in PC vs TAU
      participants at 1 year. PC appeared to be more cost effective up to a QALY
      threshold of approximately L3,000. CONCLUSIONS: Trial and intervention procedures
      appeared to be feasible and acceptable. PC allowed patients to work on
      unaddressed problems and appears cheaper than TAU. TRIAL REGISTRATION: Controlled
      Trials.com ISRCTN21615909.

PMID- 24901958
TI  - Electrochemical study of the fungicide acibenzolar-s-methyl and its voltammetric
      determination in environmental samples.
AB  - The electrochemical behavior of new generation fungicide acibenzolar-s-methyl (S
      methyl 1,2,3-benzothiadiazole-7-carbothioate, ASM) on the hanging mercury drop
      electrode (HMDE) was investigated using square wave adsorptive stripping
      voltammetry. This method of determination is based on the irreversible reduction
      of ASM at the HMDE. The well-defined ASM peak was observed at -0.4 V (vs.
      Ag/AgCl) in BR buffer at pH 2.2. The reduction peak current was proportional to
      concentration of ASM from 1.0 * 10(-8) to 6.0 * 10(-8) mol L(-1) with detection
      and quantification limit 3.0 * 10(-9) and 1.0 * 10(-8) mol L(-1), respectively.
      The applicability of the developed method for analysis of spiked samples of tap
      water, river water, and soil is illustrated. The effect of adsorption on the
      mercury electrode was studied in detail using the AC impedance method. Possible
      interferences with other common pesticides and heavy metal ions were examined.
      Clarification of the electrode mechanism was made using cyclic voltammetry (CV)
      technique.

PMID- 24901959
TI  - Validation of a multiclass multiresidue method and monitoring results for 210
      pesticides in fruits and vegetables by gas chromatography-triple quadrupole mass
      spectrometry.
AB  - A rapid, sensitive, accurate and reliable multiresidue method for the
      identification and quantification of 210 relevant pesticides in four
      representative fruit and vegetable commodities (tomato, potato, spring onion and
      orange) has been developed and validated by gas chromatography in tandem with
      triple quadrupole mass spectrometry. The method has been fully validated and
      applied to 292 samples from different countries. Prior to instrumental analysis,
      an extraction procedure based on a sample extraction of multiclass analytes,
      using the ethyl acetate method was employed. Mass spectrometric conditions were
      individually optimized for each compound in the selected reaction monitoring
      (SRM) mode to achieve maximum sensitivity. The pesticides were separated in less
      than 25 min. This was followed by an exhaustive control of the retention times.
      The Retention Time Locking Method was applied, working at a constant pressure
      throughout the analysis. System maintenance was reduced by using a purged
      capillary flow device that provided backflush capabilities by reversing column
      flow immediately after elution of the last compound of interest. Istotopically
      labelled internal standards were employed to improve the quality of the
      analytical results.

PMID- 24901960
TI  - Construction and functional analysis of Trichoderma harzianum mutants that
      modulate maize resistance to the pathogen Curvularia lunata.
AB  - Agrobacterium tumefaciens-mediated transformation (ATMT) was used to generate an
      insertional mutant library of the mycelial fungus Trichoderma harzianum. From a
      total of 450 mutants, six mutants that showed significant influence on maize
      resistance to C. lunata were analyzed in detail. Maize coated with these mutants
      was more susceptible to C. lunata compared with those coated with a wild-type
      (WT) strain. Similar to other fungal ATMT libraries, all six mutants were single
      copy integrations, which occurred preferentially in noncoding regions (except two
      mutants) and were frequently accompanied by the loss of border sequences. Two
      mutants (T66 and T312) that were linked to resistance were characterized further.
      Maize seeds coated with T66 and T312 were more susceptible to C. lunata than
      those treated with WT. Moreover, the mutants affected the resistance of maize to
      C. lunata by enhancing jasmonate-responsive gene expression. T66 and T312 induced
      maize resistance to C. lunata infection through a jasmonic acid-dependent
      pathway.

PMID- 24901961
TI  - Modelling the biphasic sorption of simazine, imidacloprid, and boscalid in
      water/soil systems.
AB  - The sorption kinetics of simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4
      diamine), imidacloprid (1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2
      ylideneamine), and boscalid (2-chloro-N-(4'-chlorobiphenyl-2-yl)nicotinamide),
      three pesticides of wide use in agriculture, was determined in five different
      water/soil systems over a time interval from the initial few seconds to about 1
      month. In all the experiments, sorption kinetics showed a biphasic pattern
      characterized by an initial, relatively short phase with a high sorption rate and
      a later phase with much a lower sorption rate. Initial sorption capacity
      increased with soil organic carbon content and with sorbate hydrophobicity. We
      postulate that the first phase of the process involves a fast second-order
      sorption reaction on superficial sites of soil particles, whereas the second
      phase depends on diffusion-controlled migration to internal binding sites. A
      kinetic equation based on this hybrid model accurately fitted all data sets. Less
      satisfactory results were obtained employing the pseudo-first order, pseudo
      second order, Elovich, two site non-equilibrium, or Weber-Morris equation. The
      superior performance of the hybrid model for describing boscalid sorption
      probably reflects the high hydrophobic character and consequent low diffusion
      rates of this compound. The accuracy of modelling was in any case strongly
      dependent on the time interval considered.

PMID- 24901962
TI  - Kinetics of metribuzin release from bentonite-polymer composites in water.
AB  - A series of bentonite polymer-composites (BPCs) loaded with metribuzin were
      studied for their controlled release in aqueous medium. The release of active
      ingredient from BPCs was significantly lower as compared to commercial metribuzin
      formulation. The results revealed that the cumulative metribuzin release was
      highest (81%) from the BPCs containing 8% clay (commercial bentonite) and 2%
      metribuzin which correspond to the lowest (14 days) half-life values i.e., time
      required for 50% release of active ingredient (t1/2). The metribuzin release from
      the BPCs decreased with increased concentration of clays in polymer matrix and
      the release was further decreased with BPCs prepared with pure nano-bentonite.
      BPCs containing 12% clay and 2% metribuzin showed maximum t1/2 values i.e., 25
      and 51 days for commercial bentonite and pure nano-bentonite as clay sources,
      respectively. The differential behaviour in the metribuzin release rates from
      BPCs was ascribed due to variations in crosslinking of metribuzin in the
      composites. As metribuzin release was found to be slower in BPCs compared to
      commercial formulation, it could be used for control of weeds tailored to
      different crops.

PMID- 24901963
TI  - Use of different organic wastes in reducing the potential leaching of propanil,
      isoxaben, cadusafos and pencycuron through the soil.
AB  - In this study, we examined the effect of four different organic wastes (OW)
      composted sheep manure (CSM), spent coffee grounds (SCG), composted pine bark
      (CPB) and coir (CR)-on the potential groundwater pollution of propanil and
      isoxaben (herbicides), cadusafos (insecticide) and pencycuron (fungicide) under
      laboratory conditions. For this purpose, leaching studies were conducted using
      disturbed soil columns filled with a clay loam soil (Hipercalcic calcisol). The
      addition of organic matter (OM) drastically reduced the movement of the studied
      pesticides. The results obtained point to the interest in the use of agro
      industrial and composted OW in reducing the groundwater pollution by pesticide
      drainage.

PMID- 24901964
TI  - Microbial response to repeated treatments of manure containing sulfadiazine and
      chlortetracycline in soil.
AB  - Substantive addition of antibiotic-contaminated manure to agricultural soil may
      lead to "persistent" residues of antibiotics and may affect soil health.
      Therefore, this study examines the effects of repeated manure treatments
      containing sulfadiazine (SDZ) and chlortetracycline (CTC) residues, both
      individually and combined, on the functional diversity and structure of soil
      microbial communities in the soils under laboratory conditions. The average well
      color development (AWCD), Simpson diversity index (1/D, dominant populations),
      Shannon-Wiener diversity index (H', richness), and McIntosh diversity index (U,
      evenness) in the antibiotics-treated soils decreased in the first 60-day
      treatment and then gradually recovered or even exceeded the initial level in the
      unamended soils with increasing treatment frequency. A total of 11 specific bands
      in temperature gradient gel electrophoresis (TGGE) profiles were observed and
      sequence analyzed for five repeated treatments, and most of them belonged to the
      phyla Firmicutes, Actinobacteria, and Proteobacteria. These results indicate that
      repeated treatments of manure containing SDZ and CTC residues can alter soil
      microbial community structure, although they have a temporary suppression effect
      on soil microbial functional diversity.

PMID- 24901965
TI  - Ultrastructural changes in the rabbit liver induced by carbamate insecticide
      bendiocarb.
AB  - Carbamates (CB) are used as insecticides and some of them have been registered as
      human drugs. The mechanism of CB poisoning involves reversible inhibition of
      acetylcholine esterase. In the present study, we investigated changes in liver
      ultrastructure in rabbits (Oryctolagus cuniculus) which were administered
      bendiocarb for 3, 10, 20, and 30 days. Rabbits in all experimental groups
      received capsules of bendiocarb (96% Bendiocarb, Bayer, Germany) per os daily at
      a dose of 5 mg/kg of body weight, and after day 11 received the same dose every
      48 h. The observed changes were only moderate, focal, and the effect on the liver
      was not uniform. On the third day of the experiment, injured hepatocytes had
      dilated bile capillaries with reduced microvilli. There were no visible
      alterations in the intercellular contacts. Nuclei of these cells were irregular
      in shape. Many hepatocytes showed considerable increase in the number of
      peroxisomes. On day 10 of the experiment, the number of peroxisomes was reduced.
      Other changes, such as dilated rough endoplasmic reticulum and proliferation of
      smooth endoplasmic reticulum were observed on day 20. The number of lipid
      droplets in hepatocytes gradually increased. Usually they were present in low
      numbers, but on day 30 of the experiment their number increased significantly.
      They coalesced and formed a single lipid droplet which changed the shape of the
      nuclei. The results presented in this study indicate that both short and long
      term administration of bendiocarb affects the liver ultrastructure. At the same
      time we also observed rapid onset of regeneration of the damaged tissue through
      activation of hepatocytes and oval cells.

PMID- 24901966
TI  - Environmental fate of tetracycline resistance genes originating from swine
      feedlots in river water.
AB  - Tetracyclines are antibiotics commonly used in swine farms to treat disease and
      promote growth. However, there are growing concerns regarding the discharge of
      animal feces into the environment owing to the potential for development and
      dissemination of tetracycline resistance genes (TRGs). In this study, farming
      wastewater from one Chinese swine farm as well as river water from seven
      locations downstream of the farm was sampled. Polymerase chain reaction (PCR)
      showed that 12 TRGs, including six efflux pump genes (tet(B), tet(C), tet(D),
      tet(E), tet(G) and tet(L)), five ribosomal protection proteins (RPPs) genes
      (tet(O), tet(M), tet(Q), tet(W) and tet(S)), and one enzymatic modification gene
      (tet(X)), were present in all wastewater and river water samples. Quantitative
      real-time PCR (qPCR) showed that the abundance of tet(C), tet(X), tet(O), tet(M),
      tet(Q) and tet(W) decreased with downstream flow. Among the detected TRGs, tet(C)
      had the highest abundance, ranging from 459.5 copies/16S rRNA gene copies in
      wastewater to 33.8 copies/16S rRNA gene copies in river water samples collected
      from the last location. Furthermore, pig-specific Bacteroidales 16S rRNA genetic
      marker was quantified by qPCR to determine the level of fecal pollution in the
      river water. Bivariate correlation analysis confirmed that the total relative
      abundance of the six TRGs was significantly correlated with the level of swine
      feces in the aquatic environment (R(2) = 0.63, P < 0.05), suggesting that swine
      feces mainly contributed to the spread of TRGs in the river water.

PMID- 24901967
TI  - Scalp nodule in an elderly woman-quiz case.

PMID- 24901969
TI  - Tailored bifunctional polymer for plutonium monitoring.
AB  - Monitoring of actinides with sophisticated conventional methods is affected by
      matrix interferences, spectral interferences, isobaric interferences, polyatomic
      interferences, and abundance sensitivity problems. To circumvent these
      limitations, a self-supported disk and membrane-supported bifunctional polymer
      were tailored in the present work for acidity-dependent selectivity toward
      Pu(IV). The bifunctional polymer was found to be better than the polymer
      containing either a phosphate group or a sulfonic acid group in terms of (i)
      higher Pu(IV) sorption efficiency at 3-4 mol L(-1) HNO3, (ii) selective
      preconcentration of Pu(IV) in the presence of a trivalent actinide such as
      Am(III), and (iii) preferential sorption of Pu(IV) in the presence of a large
      excess of U(VI). The bifunctional polymer was formed as a self-supported matrix
      by bulk polymerization and also as a 1-2 MUm thin layer anchored on a microporous
      poly(ether sulfone) by surface grafting. The proportions of sulfonic acid and
      phosphate groups in both the self-supported disk and membrane-supported
      bifunctional polymer were found to be the same as expected from the mole
      proportions of monomers in polymerizing solutions used for syntheses. alpha
      radiography by a solid-state nuclear track detector indicated fairly homogeneous
      anchoring of the bifunctional polymer on the surface of the membrane. Pu(IV)
      preconcentrated on a single bifunctional bead was used for determination of the
      Pu isotopic composition by thermal ionization mass spectrometry. The membrane
      supported bifunctional polymer was used for preconcentration and subsequent
      quantification of Pu(IV) by alpha spectrometry using the absolute efficiency at a
      fixed counting geometry. The analytical performance of the membrane-supported
      bifunctional-polymer-based alpha spectrometry method was found to be highly
      reproducible for assay of Pu(IV) in a variety of complex samples. 

PMID- 24901968
TI  - Microbial succession in the gut: directional trends of taxonomic and functional
      change in a birth cohort of Spanish infants.
AB  - In spite of its major impact on life-long health, the process of microbial
      succession in the gut of infants remains poorly understood. Here, we analyze the
      patterns of taxonomic and functional change in the gut microbiota during the
      first year of life for a birth cohort of 13 infants. We detect that individual
      instances of gut colonization vary in the temporal dynamics of microbiota
      richness, diversity, and composition at both functional and taxonomic levels.
      Nevertheless, trends discernible in a majority of infants indicate that gut
      colonization occurs in two distinct phases of succession, separated by the
      introduction of solid foods to the diet. This change in resource availability
      causes a sharp decrease in the taxonomic richness of the microbiota due to the
      loss of rare taxa (p = 2.06e-9), although the number of core genera shared by all
      infants increases substantially. Moreover, although the gut microbial succession
      is not strictly deterministic, we detect an overarching directionality of change
      through time towards the taxonomic and functional composition of the maternal
      microbiota. Succession is however not complete by the one year mark, as
      significant differences remain between one-year-olds and their mothers in terms
      of taxonomic (p = 0.009) and functional (p = 0.004) microbiota composition, and
      in taxonomic richness (p = 2.76e-37) and diversity (p = 0.016). Our results also
      indicate that the taxonomic composition of the microbiota shapes its functional
      capacities. Therefore, the observed inter-individual variability in taxonomic
      composition during succession is not fully compensated by functional equivalence
      among bacterial genera and may have important physiological consequences.
      Finally, network analyses suggest that positive interactions among core genera
      during community assembly contribute to ensure their permanence within the gut,
      and highlight an expansion of complexity in the interactions network as the core
      of taxa shared by all infants grows following the introduction of solid foods.

PMID- 24901972
TI  - Stapled haemorrhoidopexy: correlation among histology, intraoperative morphology
      and interindividual anatomic variability in muco-haemorrhoidal prolapse.
AB  - PURPOUSE: The Authors correlated intraoperative mucohaemorrhoidal prolapse
      morphology, specimen histology, anal canal length and purse-string height.
      METHODS: Between September-November 2010, 18 patients (9 grade III; 9 grade IV
      haemorrhoids) underwent stapled haemorrhoidopexy. Mean age was 54 years (range 38
      78).Proctoscopic prolapse morphology, anal canal length, pursestring height and
      external component were evaluated intraoperatively and specimens sent for
      histology. RESULTS: Intraoperative findings were as follows: 2/18 patients showed
      no procidentia, 2/18 'haemorrhoid type' prolapse, 14/18 'rectal type' prolapse.
      Mean anal canal lenght was 3.5 cm (range 2.5-4.5); mean purse-string height was
      4.5 cm from the dentate line (range 3.5-5.5); 10/18 patients carried external
      component. Histology showed mucosa/submucosa in 4/18 cases, muscolaris propria in
      9/18, perivisceral fat in 5/18. No procidentia/'haemorrhoid type' prolapse showed
      only mucosa/submucosa at histolgy; a 'rectal type' morphology showed at least the
      muscolaris propria. An anal canal > 3.5 cm related to 'haemorrhoid type'
      prolapse, a pursestring <= 4 cm and mucosa/submucosa at histology. An anal canal
      <= 3.5 cm related to 'rectal type' prolapse, a purse string > 4 cm from dentate
      line and at least the muscolaris propria. One patient required analgesics for >7
      days. At three months, 1/18 patient presented urgency, 2/18 stool clustering. In
      1/18 patient a moderate grade of external component persisted. DISCUSSION: A
      possible correlation among anoscopic phenotype, specimen histology, pursestring
      height, might exist and influence clinical outcomes. CONCLUSIONS: A positive
      correlation between specimen thickness, purse-string height and 'rectal type'
      morphology was found. Patients with higher anal canal showed haemorrhoidal
      pattern of prolapse, a lower purse-string and mucosa/submucosa at
      histology.Intraoperative prolapsing tissue morphology could represent a further
      criteria for surgical decision.

PMID- 24901973
TI  - Prevalence of upper- and lower-lid-wiper epitheliopathy in contact lens wearers
      and non-wearers.
AB  - OBJECTIVE: To report lid-wiper epitheliopathy (LWE)-like staining at the lower
      eyelid margin (lower-LWE) and to determine the prevalence of LWE (upper-LWE) and
      lower-LWE in contact lens (CL) wearers and non-CL wearers. METHODS: Four hundred
      forty-three eyes of 229 non-CL wearers, 405 eyes of 208 soft CL wearers, and 135
      eyes of 71 rigid gas permeable CL wearers were studied. Lissamine green and
      fluorescein (FL) staining were used to assess the degree of LWEs, tear break-up
      time (BUT), and cornea-conjunctival staining (FL-S). The correlations between the
      prevalence of LWEs and the other factors were evaluated. RESULTS: The prevalence
      of lower-LWE was significantly higher (39.5%) than upper-LWE in non-CL wearers
      (upper-LWE; 12.0%; P<0.001). The prevalence of both upper- and lower-LWE were
      significantly correlated with age and FL-S, but not sex and BUT, in non-CL
      wearers. The prevalence of both upper- and lower-LWE was significantly higher in
      younger than older subjects (P<0.001). Upper- and lower-LWE were detected in a
      higher percentage of CL wearers than in non-CL wearers (P<0.001). CONCLUSION: Our
      results indicate that examination of the lower eyelid margin would be preferable
      to that of the upper eyelid margin in studies of LWE.

PMID- 24901975
TI  - Automatic biometry of the anterior segment during accommodation imaged by optical
      coherence tomography.
AB  - OBJECTIVE: To test accuracy and repeatability of a software algorithm that
      performs automatic biometry of the anterior segment of the human eye imaged with
      long scan depth optical coherence tomography (OCT). METHODS: The ocular anterior
      segment imaging was performed with custom-built long scan depth OCT. An automatic
      software algorithm including boundary segmentation, image registration, and
      optical correction was developed for fast and reliable biometric measurements
      based on the OCT images. The boundary segmentation algorithm mainly used the
      gradient information of images and applied the shortest path search based on the
      dynamic programming to optimize the edge finding. The automatic algorithm was
      validated by comparison of the biometric dimensions between automatic and manual
      measurements and repeatability study. RESULTS: Biometric dimensions of the
      anterior segment, including central corneal thickness, anterior chamber depth,
      pupil diameter, crystalline lens thickness, and radii of curvature of the
      anterior and posterior surfaces of lens, were obtained by the automatic algorithm
      successfully. There were no significant differences between the automatic and
      manual measurements for all biometric dimensions. The intraclass correlation
      coefficients (ICC) of agreement between automatic and manual measurements ranged
      from 0.85 to 0.98. The coefficients of repeatability and ICC for all automatic
      dimensions were satisfactory (1.1%-6.1% and 0.663-0.990, respectively).
      CONCLUSIONS: The high accuracy, good repeatability, and fast execution speed for
      automatic measurement of the anterior segment dimensions on the OCT images were
      demonstrated. The application of this automatic biometry is promising for
      investigating dynamic changes of human anterior segment during accommodation in
      real time.

PMID- 24901974
TI  - Improving adherence to national recommendations for zoster vaccination through
      simple interventions.
AB  - OBJECTIVE: In 2011, 15.8% of eligible patients in the United States were
      vaccinated against herpes zoster (HZ). To increase the usage of the HZ vaccine by
      studying physicians' knowledge, attitudes, practices, and perceived obstacles
      after interventions to overcome barriers. METHODS: General internal medicine
      physicians were surveyed with a cross-sectional internet survey from October to
      December 2011 before interventions to increase the use of the HZ vaccine and 1
      year later. Interventions included education, increasing availability at the
      medical center pharmacy, and electronic medical record reminders. Outcome
      measures included changes in knowledge, attitudes, and practices, and perceived
      barriers. McNemar chi-square tests were used to compare the changes from the
      baseline survey for physicians who completed the follow-up survey. RESULTS:
      Response rate for the baseline study was 33.5% (89/266) and for the follow-up was
      29.8% (75/252). Fifty-five completed both surveys. There was a decrease from 57%
      at baseline to 40% at follow-up in the proportion of physicians who reported that
      less than 10% of their patients were vaccinated. They were more likely to know
      the HZ annual incidence (30% baseline; 70% follow-up; P=0.02), and report having
      educational information for physicians (7% baseline; 27% follow-up; P=0.003). The
      top helpful intervention was nursing administration of the vaccine. Average
      monthly HZ vaccine usage in the affiliated outpatient pharmacy increased in 10
      months between surveys by 156% compared with the 3 months before the baseline
      survey. CONCLUSIONS: Interventions implemented during the study led to an
      increase in physicians' basic knowledge of the HZ vaccine and an increase in
      usage at the affiliated pharmacy.

PMID- 24901977
TI  - A new dusts sensor for cultural heritage applications based on image processing.
AB  - In this paper, we propose a new sensor for the detection and analysis of dusts
      (seen as powders and fibers) in indoor environments, especially designed for
      applications in the field of Cultural Heritage or in other contexts where the
      presence of dust requires special care (surgery, clean rooms, etc.). The
      presented system relies on image processing techniques (enhancement, noise
      reduction, segmentation, metrics analysis) and it allows obtaining both
      qualitative and quantitative information on the accumulation of dust. This
      information aims to identify the geometric and topological features of the
      elements of the deposit. The curators can use this information in order to design
      suitable prevention and maintenance actions for objects and environments. The
      sensor consists of simple and relatively cheap tools, based on a high-resolution
      image acquisition system, a preprocessing software to improve the captured image
      and an analysis algorithm for the feature extraction and the classification of
      the elements of the dust deposit. We carried out some tests in order to validate
      the system operation. These tests were performed within the Sistine Chapel in the
      Vatican Museums, showing the good performance of the proposed sensor in terms of
      execution time and classification accuracy. 

PMID- 24901976
TI  - Application of adipose-derived stem cells on scleral contact lens carrier in an
      animal model of severe acute alkaline burn.
AB  - PURPOSE: To evaluate the therapeutic effect of human adipose-derived stem cells
      (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of
      ocular alkaline burn. MATERIALS AND METHODS: After inducing alkaline burn in 11
      New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of
      5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1
      eye. Each eye was examined and photographed for corneal vascularization,
      opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1
      month, rabbits were killed and the corneas were removed and cut in half for
      electron and light microscopy examination. RESULTS: Human adipose-derived stem
      cells were attached to SCL surface and confluent easily. Human adipose-derived
      stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity,
      corneal neovascularization relative to SCL eyes. Both groups showed no
      symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and
      developed severe symblepharon. CONCLUSION: Human adipose-derived stem cells on
      SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn
      injury in rabbits.

PMID- 24901978
TI  - Flexible unicast-based group communication for CoAP-enabled devices.
AB  - Smart embedded objects will become an important part of what is called the
      Internet of Things. Applications often require concurrent interactions with
      several of these objects and their resources. Existing solutions have several
      limitations in terms of reliability, flexibility and manageability of such groups
      of objects. To overcome these limitations we propose an intermediately level of
      intelligence to easily manipulate a group of resources across multiple smart
      objects, building upon the Constrained Application Protocol (CoAP). We describe
      the design of our solution to create and manipulate a group of CoAP resources
      using a single client request. Furthermore we introduce the concept of profiles
      for the created groups. The use of profiles allows the client to specify in more
      detail how the group should behave. We have implemented our solution and
      demonstrate that it covers the complete group life-cycle, i.e., creation,
      validation, flexible usage and deletion. Finally, we quantitatively analyze the
      performance of our solution and compare it against multicast-based CoAP group
      communication. The results show that our solution improves reliability and
      flexibility with a trade-off in increased communication overhead. 

PMID- 24901979
TI  - A solution-based temperature sensor using the organic compound CuTsPc.
AB  - An electrochemical cell using an organic compound, copper (II) phthalocyanine
      tetrasulfonic acid tetrasodium salt (CuTsPc,) has been fabricated and
      investigated as a solution-based temperature sensor. The capacitance and
      resistance of the ITO/CuTsPc solution/ITO chemical cell has been characterized as
      a function of temperature in the temperature range of 25-80  degrees C. A linear
      response with minimal hysteresis is observed. The fabricated temperature sensor
      has shown high consistency and sensitive response towards a specific range of
      temperature values. 

PMID- 24901980
TI  - Sensitivity of pressure sensors enhanced by doping silver nanowires.
AB  - We have developed a highly sensitive flexible pressure sensor based on a
      piezopolymer and silver nanowires (AgNWs) composite. The composite nanofiber webs
      are made by electrospinning mixed solutions of poly(inylidene fluoride) (PVDF)
      and Ag NWs in a cosolvent mixture of dimethyl formamide and acetone. The diameter
      of the fibers ranges from 200 nm to 500 nm, as demonstrated by SEM images. FTIR
      and XRD results reveal that doping Ag NWs into PVDF greatly enhances the content
      of beta phase in PVDF. This beta phase increase can be attributed to interactions
      between the Ag NWs and the PVDF matrix, which forces the polymer chains to be
      embedded into the beta phase crystalline. The sensitivity of the pressure sensors
      agrees well with the FTIR and XRD characteristics. In our experiments, the
      measured sensitivity reached up to 30 pC/N for the nanofiber webs containing 1.5
      wt% Ag NWs, which is close to that of poly(vinylidene fluoride-trifluoroethylene)
      [P(VDF-TrFE), (77/23)]. This study may provide a new method of fabricating high
      performance flexible sensors at relatively low cost compared with sensors based
      on [P(VDF-TrFE), (77/23)]. 

PMID- 24901981
TI  - Crystallographic and magnetic structure of the perovskite-type compound BaFeO2.5:
      unrivaled complexity in oxygen vacancy ordering.
AB  - We report here on the characterization of the vacancy-ordered perovskite-type
      structure of BaFeO2.5 by means of combined Rietveld analysis of powder X-ray and
      neutron diffraction data. The compound crystallizes in the monoclinic space group
      P2(1)/c [a = 6.9753(1) A, b = 11.7281(2) A, c = 23.4507(4) A, beta = 98.813(1)
      degrees , and Z = 28] containing seven crystallographically different iron atoms.
      The coordination scheme is determined to be
      Ba7(FeO4/2)1(FeO3/2O1/1)3(FeO5/2)2(FeO6/2)1 = Ba7Fe([6])1Fe([5])2Fe([4])4O17.5
      and is in agreement with the (57)Fe Mossbauer spectra and density functional
      theory based calculations. To our knowledge, the structure of BaFeO2.5 is the
      most complicated perovskite-type superstructure reported so far (largest
      primitive cell, number of ABX2.5 units per unit cell, and number of different
      crystallographic sites). The magnetic structure was determined from the powder
      neutron diffraction data and can be understood in terms of "G-type"
      antiferromagnetic ordering between connected iron-containing polyhedra, in
      agreement with field-sweep and zero-field-cooled/field-cooled measurements.

PMID- 24901982
TI  - Strong decrease in streptomycin-resistance and absence of XDR 12 years after the
      Reorganization of the National Tuberculosis Control Program in the Central Region
      of Cameroon.
AB  - BACKGROUND: In the 1990s, resistance rates of 15% for streptomycin-resistance and
      0.6% for multidrug-resistance (MDR) were reported from the Central Region of
      Cameroon. This work assesses drug resistant tuberculosis in this region 12 years
      after reorganization of the National Tuberculosis Control Program (NTCP).
      METHODS: This cross-sectional study was conducted from April 2010 to March 2011
      in Jamot Hospital in Yaounde, Cameroon. Only patients with smear positive
      pulmonary tuberculosis were included. Sputa were cultured and subsequently
      underwent drug susceptibility testing (DST). All consenting individuals were
      tested for their HIV status. RESULTS: A total of 665 smear positive pulmonary
      tuberculosis patients were enrolled. The HIV prevalence was 28.5% (95%CI [25.2
      32.1]). Of the 582 sputa that grew Mycobacterium tuberculosis complex species,
      DST results were obtained for 576. The overall resistance rate was 10.9%
      (63/576). The overall resistance rates for single drug resistance were: isoniazid
      resistance 4.7% (27/576), streptomycin-resistance 3.3% (19/576), rifampicin
      resistance 0.2% (1/576), kanamycin-resistance 0.2% (1/576) and ofloxacin
      resistance 0.2% (1/576). The MDR rate was 1.1% (6/576) and no extensively drug
      resistant tuberculosis (XDR) was detected. CONCLUSIONS: The data show that
      reorganization of the NTCP resulted in a strong decrease in streptomycin
      resistance and suggest that it prevented the emergence of XDR in the Central
      Region of Cameroon.

PMID- 24901985
TI  - Sensitivity of honeybee hygroreceptors to slow humidity changes and temporal
      humidity variation detected in high resolution by mobile measurements.
AB  - The moist cell and the dry cell on the antenna of the male honeybee were exposed
      to humidities slowly rising and falling at rates between -1.5%/s and +1.5%/s and
      at varying amplitudes in the 10 to 90% humidity range. The two cells respond to
      these slow humidity oscillations with oscillations in impulse frequency which
      depend not only on instantaneous humidity but also on the rate with which
      humidity changes. The impulse frequency of each cell was plotted as a function of
      these two parameters and regression planes were fitted to the data points of
      single oscillation periods. The regression slopes, which estimate sensitivity,
      rose with the amplitude of humidity oscillations. During large-amplitude
      oscillations, moist and dry cell sensitivity for instantaneous humidity and its
      rate of change was high. During small-amplitude oscillations, their sensitivity
      for both parameters was low, less exactly reflecting humidity fluctuations.
      Nothing is known about the spatial and temporal humidity variations a honeybee
      may encounter when flying through natural environments. Microclimatic parameters
      (absolute humidity, temperature, wind speed) were measured from an automobile
      traveling through different landscapes of Lower Austria. Landscape type affected
      extremes and mean values of humidity. Differences between peaks and troughs of
      humidity fluctuations were generally smaller in open grassy fields or deciduous
      forests than in edge habitats or forest openings. Overall, fluctuation amplitudes
      were small. In this part of the stimulus range, hygroreceptor sensitivity is not
      optimal for encoding instantaneous humidity and the rate of humidity change. It
      seems that honeybee's hygroreceptors are specialized for detecting large
      amplitude fluctuations that are relevant for a specific behavior, namely,
      maintaining a sufficiently stable state of water balance. The results suggest
      that optimal sensitivity of both hygroreceptors is shaped not only by humidity
      oscillation amplitudes but also according to their impact on behavior. 

PMID- 24901984
TI  - Glycogen synthase kinase (GSK) 3beta phosphorylates and protects nuclear myosin
      1c from proteasome-mediated degradation to activate rDNA transcription in early
      G1 cells.
AB  - Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription
      activation and cell cycle progression by facilitating PCAF-mediated H3K9
      acetylation, but the molecular mechanism by which NM1 is regulated remains
      unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK)
      3beta phosphorylates and stabilizes NM1, allowing for NM1 association with the
      chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the
      rDNA as active GSK3beta selectively occupies the gene. ChIP assays and
      transmission electron microscopy in GSK3beta-/- mouse embryonic fibroblasts
      indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9
      acetylation leading to a chromatin state incompatible with transcription. We
      found that GSK3beta directly phosphorylates the endogenous NM1 on a single serine
      residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation
      event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5
      and proteasome-mediated degradation. We conclude that GSK3beta-mediated
      phosphorylation of NM1 is required for pol I transcription activation. 

PMID- 24901986
TI  - Role of Na,K-ATPase alpha1 and alpha2 isoforms in the support of astrocyte
      glutamate uptake.
AB  - Glutamate released during neuronal activity is cleared from the synaptic space
      via the astrocytic glutamate/Na(+) co-transporters. This transport is driven by
      the transmembrane Na(+) gradient mediated by Na,K-ATPase. Astrocytes express two
      isoforms of the catalytic Na,K-ATPase alpha subunits; the ubiquitously expressed
      alpha1 subunit and the alpha2 subunit that has a more specific expression
      profile. In the brain alpha2 is predominantly expressed in astrocytes. The
      isoforms differ with regard to Na+ affinity, which is lower for alpha2. The
      relative roles of the alpha1 and alpha2 isoforms in astrocytes are not well
      understood. Here we present evidence that the presence of the alpha2 isoform may
      contribute to a more efficient restoration of glutamate triggered increases in
      intracellular sodium concentration [Na(+)]i. Studies were performed on primary
      astrocytes derived from E17 rat striatum expressing Na,K-ATPase alpha1 and alpha2
      and the glutamate/Na(+) co-transporter GLAST. Selective inhibition of alpha2
      resulted in a modest increase of [Na(+)]i accompanied by a disproportionately
      large decrease in uptake of aspartate, an indicator of glutamate uptake. To
      compare the capacity of alpha1 and alpha2 to handle increases in [Na(+)]i
      triggered by glutamate, primary astrocytes overexpressing either alpha1 or alpha2
      were used. Exposure to glutamate 200 uM caused a significantly larger increase in
      [Na(+)]i in alpha1 than in alpha2 overexpressing cells, and as a consequence
      restoration of [Na(+)]i, after glutamate exposure was discontinued, took longer
      time in alpha1 than in alpha2 overexpressing cells. Both alpha1 and alpha2
      interacted with astrocyte glutamate/Na(+) co-transporters via the 1st
      intracellular loop.

PMID- 24901987
TI  - Delayed effects of corticosterone on slow after-hyperpolarization potentials in
      mouse hippocampal versus prefrontal cortical pyramidal neurons.
AB  - The rodent stress hormone corticosterone changes neuronal activity in a slow and
      persistent manner through transcriptional regulation. In the rat dorsal
      hippocampus, corticosterone enhances the amplitude of calcium-dependent potassium
      currents that cause a lingering slow after-hyperpolarization (sAHP) at the end of
      depolarizing events. In this study we compared the putative region-dependency of
      the delayed effects of corticosterone (approximately 5 hrs after treatment) on
      sAHP as well as other active and passive properties of layer 2/3 pyramidal
      neurons from three prefrontal areas, i.e. the lateral orbitofrontal, prelimbic
      and infralimbic cortex, with the hippocampus of adult mice. In agreement with
      previous studies, corticosterone increased sAHP amplitude in the dorsal
      hippocampus with depolarizing steps of increasing amplitude. However, in the
      lateral orbitofrontal, prelimbic and infralimbic cortices we did not observe any
      modifications of sAHP amplitude after corticosterone treatment. Properties of
      single action potentials or % ratio of the last spike interval with respect to
      the first spike interval, an indicator of accommodation in an action potential
      train, were not significantly affected by corticosterone in all brain regions
      examined. Lastly, corticosterone treatment did not induce any lasting changes in
      passive membrane properties of hippocampal or cortical neurons. Overall, the data
      indicate that corticosterone slowly and very persistently increases the sAHP
      amplitude in hippocampal pyramidal neurons, while this is not the case in the
      cortical regions examined. This implies that changes in excitability across brain
      regions reached by corticosterone may vary over a prolonged period of time after
      stress. 

PMID- 24901989
TI  - In vitro and in silico derived relative effect potencies of ah-receptor-mediated
      effects by PCDD/Fs and PCBs in rat, mouse, and guinea pig CALUX cell lines.
AB  - For a better understanding of species-specific relative effect potencies (REPs),
      responses of dioxin-like compounds (DLCs) were assessed. REPs were calculated
      using chemical-activated luciferase gene expression assays (CALUX) derived from
      guinea pig, rat, and mouse cell lines. Almost all 20 congeners tested in the
      rodent cell lines were partial agonists and less efficacious than 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). For this reason, REPs were calculated for
      each congener using concentrations at which 20% of the maximal TCDD response was
      reached (REP20TCDD). REP20TCDD values obtained for PCDD/Fs were comparable with
      their toxic equivalency factors assigned by the World Health Organization (WHO
      TEF), while those for PCBs were in general lower than the WHO-TEF values.
      Moreover, the guinea pig cell line was the most sensitive as indicated by the 20%
      effect concentrations of TCDD of 1.5, 5.6, and 11.0 pM for guinea pig, rat, and
      mouse cells, respectively. A similar response pattern was observed using
      multivariate statistical analysis between the three CALUX assays and the WHO
      TEFs. The mouse assay showed minor deviation due to higher relative induction
      potential for 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,6,7,8
      hexachlorodibenzofuran and lower for 1,2,3,4,6,7,8-heptachlorodibenzofuran and
      3,3',4,4',5-pentachlorobiphenyl (PCB126). 2,3,7,8-Tetrachlorodibenzofuran was
      more than two times more potent in the mouse assay as compared with that of rat
      and guinea pig cells, while measured REP20TCDD for PCB126 was lower in mouse
      cells (0.05) as compared with that of the guinea pig (0.2) and rat (0.07). In
      order to provide REP20TCDD values for all WHO-TEF assigned compounds,
      quantitative structure-activity relationship (QSAR) models were developed. The
      QSAR models showed that specific electronic properties and molecular surface
      characteristics play important roles in the AhR-mediated response. In silico
      derived REP20TCDD values were generally consistent with the WHO-TEFs with a few
      exceptions. The QSAR models indicated that, e.g., 1,2,3,7,8
      pentachlorodibenzofuran and 1,2,3,7,8,9-hexachlorodibenzofuran were more potent
      than given by their assigned WHO-TEF values, and the non-ortho PCB 81 was
      predicted, based on the guinea-pig model, to be 1 order of magnitude above its
      WHO-TEF value. By combining in vitro and in silico approaches, REPs were
      established for all WHO-TEF assigned compounds (except OCDD), which will provide
      future guidance in testing AhR-mediated responses of DLCs and to increase our
      understanding of species variation in AhR-mediated effects. 

PMID- 24901988
TI  - Regulation of Hfq mRNA and protein levels in Escherichia coli and Pseudomonas
      aeruginosa by the Burkholderia cenocepacia MtvR sRNA.
AB  - Small non-coding RNAs (sRNAs) are important players of gene expression regulation
      in bacterial pathogens. MtvR is a 136-nucleotide long sRNA previously identified
      in the human pathogen Burkholderia cenocepacia J2315 and with homologues
      restricted to bacteria of the Burkholderia cepacia complex. In this work we have
      investigated the effects of expressing MtvR in Escherichia coli and Pseudomonas
      aeruginosa. Results are presented showing that MtvR negatively regulates the hfq
      mRNA levels in both bacterial species. In the case of E. coli, this negative
      regulation is shown to involve binding of MtvR to the 5'-UTR region of the hfqEc
      mRNA. Results presented also show that expression of MtvR in E. coli and P.
      aeruginosa originates multiple phenotypes, including reduced resistance to
      selected stresses, biofilm formation ability, and increased susceptibility to
      various antibiotics. 

PMID- 24901990
TI  - Potent inhibition of Junin virus infection by interferon in murine cells.
AB  - The new world arenavirus Junin virus (JUNV) is the causative agent of Argentine
      hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are
      generally resistant to peripheral infection by JUNV. The mechanism underlying the
      mouse resistance to JUNV infection is largely unknown. We have reported that
      interferon receptor knockout mice succumb to JUNV infection, indicating the
      critical role of interferon in restricting JUNV infection in mice. Here we report
      that the pathogenic and vaccine strains of JUNV were highly sensitive to
      interferon in murine primary cells. Treatment with low concentrations of
      interferon abrogated viral NP protein expression in murine cells. The replication
      of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine
      strain of JUNV displayed impaired growth in primary murine cells. Our data
      suggested a direct and potent role of host interferon response in restricting
      JUNV replication in mice. The defect in viral growth for vaccine JUNV might also
      partially explain its attenuation in mice. 

PMID- 24901992
TI  - Biaxial aromatics with face-on/edge-on stacking adaptability: an STM/STS study of
      1D nanowires assembled via rotatable ethynyls.
AB  - Scanning tunnelling microscopy/spectroscopy reveals significant electronic
      communications between edge-on biphenyl moieties of a benzene core derivatised
      biaxially with four ethynyl-biphenyls. The key to the successful assembly of
      conjugated 1D nanowires is the rotatable features of ethynyls, which allow dual
      adaptability of edge-on and face-on orientations for the aromatic rings. 

PMID- 24901991
TI  - Cytokine production but lack of proliferation in peripheral blood mononuclear
      cells from chronic Chagas' disease cardiomyopathy patients in response to T.
      cruzi ribosomal P proteins.
AB  - BACKGROUND: Trypanosoma cruzi ribosomal P proteins, P2beta and P0, induce high
      levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy
      (CCC). It is well known that these antibodies alter the beating rate of
      cardiomyocytes and provoke apoptosis by their interaction with beta1-adrenergic
      and M2-muscarinic cardiac receptors. Based on these findings, we decided to study
      the cellular immune response to these proteins in CCC patients compared to non
      infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated proliferation,
      presence of surface activation markers and cytokine production in peripheral
      blood mononuclear cells (PBMC) stimulated with P2beta, the C-terminal portion of
      P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected
      with TcVI lineage. PBMC from CCC patients cultured with P2beta or CP0 proteins,
      failed to proliferate and express CD25 and HLA-DR on T cell populations. However,
      multiplex cytokine assays showed that these antigens triggered higher secretion
      of IL-10, TNF-alpha and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells
      subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients
      not only proliferated but also became activated within the context of Th1
      response. Interestingly, T. cruzi lysate was also able to induce the secretion of
      GM-CSF by CD4+ or CD8+ T cells. CONCLUSIONS/SIGNIFICANCE: Our results showed that
      although the lack of PBMC proliferation in CCC patients in response to ribosomal
      P proteins, the detection of IL-10, TNF-alpha and GM-CSF suggests that specific T
      cells could have both immunoregulatory and pro-inflammatory potential, which
      might modulate the immune response in Chagas' disease. Furthermore, it was
      possible to demonstrate for the first time that GM-CSF was produced by PBMC of
      CCC patients in response not only to recombinant ribosomal P proteins but also to
      parasite lysate, suggesting the value of this cytokine to evaluate T cells
      responses in T. cruzi infection.

PMID- 24901993
TI  - Vanadate from air pollutant inhibits hrs-dependent endosome fusion and augments
      responsiveness to toll-like receptors.
AB  - There is a well-established association between exposure to air pollutants and
      pulmonary injuries. For example, metals found in ROFA (residual oil fly ash)
      increase susceptibility of mice as well as humans to microbial infections. In our
      research, we have found that vanadate substantially increased the response of
      several Toll-like receptors (TLRs) to stimulation with their ligands. Although
      vanadate caused generation of reactive oxygen species (ROS), the addition of ROS
      scavenger N-acetyl cysteine (NAC) had no effect on augmented lipopolysaccharide
      (LPS) stimulation. We further showed that vanadate inhibits endosome fusion. This
      effect was determined by measuring the size of endosomes, NF-kappaB activity and
      TLR4 degradation in Hrs (hepatocyte growth factor-regulated tyrosine kinase
      substrate) overexpressed cells. Moreover, we identified the role of Hrs
      phosphorylation in these processes. Based on our findings, we can conclude that
      vanadate potentiates TLR4 activity by increasing Hrs phosphorylation status,
      reducing the size of Hrs/TLR4-positive endosomes and impacting TLR4 degradation,
      thus contributing to the detrimental effects of air pollutants on human health. 

PMID- 24901994
TI  - The highly conserved bacterial RNase YbeY is essential in Vibrio cholerae,
      playing a critical role in virulence, stress regulation, and RNA processing.
AB  - YbeY, a highly conserved protein, is an RNase in E. coli and plays key roles in
      both processing of the critical 3' end of 16 S rRNA and in 70 S ribosome quality
      control under stress. These central roles account for YbeY's inclusion in the
      postulated minimal bacterial genome. However, YbeY is not essential in E. coli
      although loss of ybeY severely sensitizes it to multiple physiological stresses.
      Here, we show that YbeY is an essential endoribonuclease in Vibrio cholerae and
      is crucial for virulence, stress regulation, RNA processing and ribosome quality
      control, and is part of a core set of RNases essential in most representative
      pathogens. To understand its function, we analyzed the rRNA and ribosome profiles
      of a V. cholerae strain partially depleted for YbeY and other RNase mutants
      associated with 16 S rRNA processing; our results demonstrate that YbeY is also
      crucial for 16 S rRNA 3' end maturation in V. cholerae and that its depletion
      impedes subunit assembly into 70 S ribosomes. YbeY's importance to V. cholerae
      pathogenesis was demonstrated by the complete loss of mice colonization and
      biofilm formation, reduced cholera toxin production, and altered expression
      levels of virulence-associated small RNAs of a V. cholerae strain partially
      depleted for YbeY. Notably, the ybeY genes of several distantly related pathogens
      can fully complement an E. coli DeltaybeY strain under various stress conditions,
      demonstrating the high conservation of YbeY's activity in stress regulation.
      Taken together, this work provides the first comprehensive exploration of YbeY's
      physiological role in a human pathogen, showing its conserved function across
      species in essential cellular processes. 

PMID- 24901995
TI  - Ongoing activity in temporally coherent networks predicts intra-subject
      fluctuation of response time to sporadic executive control demands.
AB  - Can ongoing fMRI BOLD signals predict fluctuations in swiftness of a person's
      response to sporadic cognitive demands? This is an important issue because it
      clarifies whether intrinsic brain dynamics, for which spatio-temporal patterns
      are expressed as temporally coherent networks (TCNs), have effects not only on
      sensory or motor processes, but also on cognitive processes. Predictivity has
      been affirmed, although to a limited extent. Expecting a predictive effect on
      executive performance for a wider range of TCNs constituting the cingulo
      opercular, fronto-parietal, and default mode networks, we conducted an fMRI study
      using a version of the color-word Stroop task that was specifically designed to
      put a higher load on executive control, with the aim of making its fluctuations
      more detectable. We explored the relationships between the fluctuations in
      ongoing pre-trial activity in TCNs and the task response time (RT). The results
      revealed the existence of TCNs in which fluctuations in activity several seconds
      before the onset of the trial predicted RT fluctuations for the subsequent trial.
      These TCNs were distributed in the cingulo-opercular and fronto-parietal
      networks, as well as in perceptual and motor networks. Our results suggest that
      intrinsic brain dynamics in these networks constitute "cognitive readiness,"
      which plays an active role especially in situations where information for
      anticipatory attention control is unavailable. Fluctuations in these networks
      lead to fluctuations in executive control performance. 

PMID- 24901997
TI  - Chimpanzee choice rates in competitive games match equilibrium game theory
      predictions.
AB  - The capacity for strategic thinking about the payoff-relevant actions of
      conspecifics is not well understood across species. We use game theory to make
      predictions about choices and temporal dynamics in three abstract competitive
      situations with chimpanzee participants. Frequencies of chimpanzee choices are
      extremely close to equilibrium (accurate-guessing) predictions, and shift as
      payoffs change, just as equilibrium theory predicts. The chimpanzee choices are
      also closer to the equilibrium prediction, and more responsive to past history
      and payoff changes, than two samples of human choices from experiments in which
      humans were also initially uninformed about opponent payoffs and could not
      communicate verbally. The results are consistent with a tentative interpretation
      of game theory as explaining evolved behavior, with the additional hypothesis
      that chimpanzees may retain or practice a specialized capacity to adjust strategy
      choice during competition to perform at least as well as, or better than, humans
      have. 

PMID- 24901996
TI  - Environmental risk score as a new tool to examine multi-pollutants in
      epidemiologic research: an example from the NHANES study using serum lipid
      levels.
AB  - OBJECTIVE: A growing body of evidence suggests that environmental pollutants,
      such as heavy metals, persistent organic pollutants and plasticizers play an
      important role in the development of chronic diseases. Most epidemiologic studies
      have examined environmental pollutants individually, but in real life, we are
      exposed to multi-pollutants and pollution mixtures, not single pollutants.
      Although multi-pollutant approaches have been recognized recently, challenges
      exist such as how to estimate the risk of adverse health responses from multi
      pollutants. We propose an "Environmental Risk Score (ERS)" as a new simple tool
      to examine the risk of exposure to multi-pollutants in epidemiologic research.
      METHODS AND RESULTS: We examined 134 environmental pollutants in relation to
      serum lipids (total cholesterol, high-density lipoprotein cholesterol (HDL), low
      density lipoprotein cholesterol (LDL) and triglycerides) using data from the
      National Health and Nutrition Examination Survey between 1999 and 2006. Using a
      two-stage approach, stage-1 for discovery (n = 10818) and stage-2 for validation
      (n = 4615), we identified 13 associated pollutants for total cholesterol, 9 for
      HDL, 5 for LDL and 27 for triglycerides with adjustment for sociodemographic
      factors, body mass index and serum nutrient levels. Using the regression
      coefficients (weights) from joint analyses of the combined data and exposure
      concentrations, ERS were computed as a weighted sum of the pollutant levels. We
      computed ERS for multiple lipid outcomes examined individually (single-phenotype
      approach) or together (multi-phenotype approach). Although the contributions of
      ERS to overall risk predictions for lipid outcomes were modest, we found
      relatively stronger associations between ERS and lipid outcomes than with
      individual pollutants. The magnitudes of the observed associations for ERS were
      comparable to or stronger than those for socio-demographic factors or BMI.
      CONCLUSIONS: This study suggests ERS is a promising tool for characterizing
      disease risk from multi-pollutant exposures. This new approach supports the need
      for moving from a single-pollutant to a multi-pollutant framework.

PMID- 24901998
TI  - Acidic amino acids in the first intracellular loop contribute to voltage- and
      calcium- dependent gating of anoctamin1/TMEM16A.
AB  - Anoctamin1 (Ano1, or TMEM16A) is a Ca2+-activated chloride channel that is gated
      by both voltage and Ca2+. We have previously identified that the first
      intracellular loop that contains a high density of acidic residues mediates
      voltage- and calcium-dependent gating of Ano1. Mutation of the four consecutive
      glutamates (444EEEE447) inhibits the voltage-dependent activation of Ano1,
      whereas deletion of these residues decreases apparent Ca2+ sensitivity. In the
      present study, we further found that deletion of 444EEEEEAVKD452 produced a more
      than 40-fold decrease in the apparent Ca2+ sensitivity with altered activation
      kinetics. We then systematically mutated each acidic residue into alanine, and
      analyzed the voltage- and calcium dependent activation of each mutation.
      Activation kinetics of wild type Ano1 consisted of a fast component (taufast)
      that represented voltage-dependent mode, and a slow component (tauslow) that
      reflected the Ca2+-dependent modal gating. E444A, E445A, E446A, E447A, E448A, and
      E457A mutations showed a decrease in the taufast, significantly inhibited voltage
      dependent activation of Ano1 in the absence of Ca2+, and greatly shifted the G-V
      curve to the right, suggesting that these glutamates are involved in voltage
      gating of Ano1. Furthermore, D452A, E464A, E470A, and E475A mutations that did
      not alter voltage-dependent activation of the channel, significantly decreased
      Ca2+ dependence of G-V curve, exhibited an increase in the tauslow, and produced
      a 2-3 fold decrease in the apparent Ca2+ sensitivity, suggesting that these
      acidic residues are involved in Ca2+-dependent gating of the channel. Our data
      show that acidic residues in the first intracellular loop are the important
      structural determinant that couples the voltage and calcium dependent gating of
      Ano1. 

PMID- 24902001
TI  - Binary diamondoid building blocks for molecular gels.
AB  - Adamantane is a type of diamondoid molecules that has a cage or globular shape
      with a diameter of 6.34 +/- 0.04 A.8 Anisotropic interactions between these truly
      nanoscopic particles can be induced through the derivatization of the diamondoid
      cage. Here we explore the gelation of paired systems of adamantane where
      attractions are introduced through van der Waals forces and hydrogen bonding.
      Gels are produced through the mixing of 1-adamantanecarboxylic acid (A1C) and 1
      adamantylamine (A1N). Upon mixing dimethyl sulfoxide solutions of these molecules
      at vanishing concentrations, these diamondoid molecules rapidly precipitate. A
      space-filling gel of the resulting aggregates is observed at approximately 3% by
      weight. These resulting gels have elastic moduli of 10(2)-10(4) Pa in the 3-7 wt
      % concentration range. At a 1:1 mol ratio of 1-adamantanecarboxylic acid (A1C)
      and 1-adamantylamine (A1N), the gel's elastic modulus and yield stress increase
      as volume fractions phi(x) and phi(y) with x ~ 4.2 and y ~ 3.5. The dependencies
      of moduli and yield stress on the volume fraction display characteristics of
      colloidal gels. Transmission electron microscope (TEM) images indicate that the
      gels are formed from a network of interwoven and branched fibers which are
      composed of ~30 nm crystallites that have undergone oriented aggregation to form
      fibers. 

PMID- 24902000
TI  - Photoemission spectra and density functional theory calculations of 3d transition
      metal-aqua complexes (Ti-Cu) in aqueous solution.
AB  - Photoelectron spectroscopy measurements and density functional calculations are
      combined to determine the lowest electron binding energies of first-row
      transition-metal aqua ions, titanium through copper, with 3d(1) through 3d(9)
      electronic configurations, in their most common oxidation states. Vertical
      ionization energies are found to oscillate considerably between 6.76 and 9.65 eV
      for the dications and between 7.05 and 10.28 eV for the respective trivalent
      cations. The metal cations are modeled as [M(H2O)n](q+) clusters (q = 2, 3, and
      4; n = 6 and 18) surrounded by continuum solvent. The performance of 10 exchange
      correlation functionals, two GGAs, three MGGAs, two HGGAs and three HMGGAs,
      combined with the MDF10(ECP)/6-31+G(d,p) basis set is assessed for 11 M-O bond
      distances, 10 vertical ionization energies, 6 adiabatic ionization energies, and
      the associated reorganization free energies. We find that for divalent cations
      the HGGA and HMGGA functionals in combination with the 18 water model show the
      best agreement with experimental vertical ionization energies and geometries; for
      trivalent ions, the MGGA functionals perform best. The corresponding
      reorganization free energies (lambdao) of the oxidized ions are significantly
      underestimated with all DFT functionals and cluster models. This indicates that
      the structural reorganization of the solvation shell upon ionization is not
      adequately accounted for by the simple solvation models used, emphasizing the
      importance of extended sampling of thermally accessible solvation structures for
      an accurate computation of this quantity. The photoelectron spectroscopy
      measurements reported herein provide a comprehensive set of transition-metal
      redox energetic quantities for future electronic structure benchmarks. 

PMID- 24902002
TI  - Fe3O4 nanosphere@microporous organic networks: enhanced anode performances in
      lithium ion batteries through carbonization.
AB  - Very thin microporous organic networks were formed on the surface of Fe3O4
      nanospheres by Sonogashira coupling of tetra(4-ethynylphenyl)methane and 1,4
      diiodobenzene. The thickness was controlled by screening the number of building
      blocks. Through carbonization, Fe3O4@C composites were prepared. The Fe3O4@C
      composites with 4-6 nm carbon thickness showed promising reversible discharge
      capacities of up to 807 mA h g(-1) and enhanced electrochemical stability. 

PMID- 24901999
TI  - Tumor suppressor DYRK1A effects on proliferation and chemoresistance of AML cells
      by downregulating c-Myc.
AB  - Acute myeloid leukemia (AML), caused by abnormal proliferation and accumulation
      of hematopoietic progenitor cells, is one of the most common malignancies in
      adults. We reported here DYRK1A expression level was reduced in the bone marrow
      of adult AML patients, comparing to normal controls. Overexpression of DYRK1A
      inhibited the proliferation of AML cell lines by increasing the proportion of
      cells undergoing G0/G1 phase. We reasoned that the proliferative inhibition was
      due to downregulation of c-Myc by DYRK1A, through mediating its degradation.
      Moreover, overexpression of c-Myc markedly reversed AML cell growth inhibition
      induced by DYRK1A. DYRK1A also had significantly lower expression in
      relapsed/refractory AML patients, comparing to newly-diagnosed AML patients,
      which indicated the role of DYRK1A in chemoresistance of AML. Our study provided
      functional evidences for DYRK1A as a potential tumor suppressor in AML. 

PMID- 24902004
TI  - Intimate partner violence and the utilization of maternal health care services in
      Nigeria.
AB  - Our aim in this study is to examine the association between women's lifetime
      experiences of physical, sexual, and emotional intimate partner violence (IPV)
      and the use of maternal health care services. We used data from the 2008 Nigeria
      Demographic and Health Survey. Analysis was based on responses from 17,476 women
      (for antenatal care [ANC]) and 17,412 (for delivery assisted by a skilled health
      provider) who had had deliveries in the 5 years preceding the survey. We found an
      overall IPV prevalence rate of 33.4%. Physical IPV was associated with low use of
      ANC. Emotionally abused women were less likely to use delivery assistance from
      skilled health care providers. Based on our findings, we suggest the importance
      of designing interventions to address the health care needs of women who have
      experienced violence from their partners. 

PMID- 24902003
TI  - Place cell rate remapping by CA3 recurrent collaterals.
AB  - Episodic-like memory is thought to be supported by attractor dynamics in the
      hippocampus. A possible neural substrate for this memory mechanism is rate
      remapping, in which the spatial map of place cells encodes contextual information
      through firing rate variability. To test whether memories are stored as
      multimodal attractors in populations of place cells, recent experiments morphed
      one familiar context into another while observing the responses of CA3 cell
      ensembles. Average population activity in CA3 was reported to transition
      gradually rather than abruptly from one familiar context to the next, suggesting
      a lack of attractive forces associated with the two stored representations. On
      the other hand, individual CA3 cells showed a mix of gradual and abrupt
      transitions at different points along the morph sequence, and some displayed
      hysteresis which is a signature of attractor dynamics. To understand whether
      these seemingly conflicting results are commensurate with attractor network
      theory, we developed a neural network model of the CA3 with attractors for both
      position and discrete contexts. We found that for memories stored in overlapping
      neural ensembles within a single spatial map, position-dependent context
      attractors made transitions at different points along the morph sequence. Smooth
      transition curves arose from averaging across the population, while a
      heterogeneous set of responses was observed on the single unit level. In
      contrast, orthogonal memories led to abrupt and coherent transitions on both
      population and single unit levels as experimentally observed when remapping
      between two independent spatial maps. Strong recurrent feedback entailed a
      hysteretic effect on the network which diminished with the amount of overlap in
      the stored memories. These results suggest that context-dependent memory can be
      supported by overlapping local attractors within a spatial map of CA3 place
      cells. Similar mechanisms for context-dependent memory may also be found in other
      regions of the cerebral cortex. 

PMID- 24902005
TI  - Nutritional requirements of sheep, goats and cattle in warm climates: a meta
      analysis.
AB  - The objective of the study was to update energy and protein requirements of
      growing sheep, goats and cattle in warm areas through a meta-analysis study of
      590 publications. Requirements were expressed on metabolic live weight
      (MLW=LW0.75) and LW1 basis. The maintenance requirements for energy were 542.64
      and 631.26 kJ ME/kg LW0.75 for small ruminants and cattle, respectively, and the
      difference was significant (P<0.01). The corresponding requirement for 1 g gain
      was 24.3 kJ ME without any significant effect of species. Relative to LW0.75,
      there was no difference among genotypes intra-species in terms of ME requirement
      for maintenance and gain. However, small ruminants of warm and tropical climate
      appeared to have higher ME requirements for maintenance relative to live weight
      (LW) compared with temperate climate ones and cattle. Maintenance requirements
      for protein were estimated via two approaches. For these two methods, the data in
      which retained nitrogen (RN) was used cover the same range of variability of
      observations. The regression of digestible CP intake (DCPI, g/kg LW0.75) against
      RN (g/kg LW0.75) indicated that DCP requirements are significantly higher in
      sheep (3.36 g/kg LW0.75) than in goats (2.38 g/kg LW0.75), with cattle
      intermediate (2.81 g/kg LW0.75), without any significant difference in the
      quantity of DCPI/g retained CP (RCP) (40.43). Regressing metabolisable protein
      (MP) or minimal digestible protein in the intestine (PDImin) against RCP showed
      that there was no difference between species and genotypes, neither for the
      intercept (maintenance=3.51 g/kg LW0.75 for sheep and goat v. 4.35 for cattle)
      nor for the slope (growth=0.60 g MP/g RCP). The regression of DCP against ADG
      showed that DCP requirements did not differ among species or genotypes. These new
      feeding standards are derived from a wider range of nutritional conditions
      compared with existing feeding standards as they are based on a larger database.
      The standards seem to be more appropriate for ruminants in warm and tropical
      climates around the world. 

PMID- 24902006
TI  - Overview and management of dermatologic events associated with targeted therapies
      for medullary thyroid cancer.
AB  - BACKGROUND: Treatment options for patients with advanced or metastatic medullary
      thyroid cancer (MTC) have, in recent years, expanded with the approval of two
      tyrosine kinase inhibitors (TKIs): vandetanib and cabozantinib. Other agents,
      including TKIs, are under clinical investigation for MTC. Although patients
      treated with TKIs are at risk of developing dermatologic adverse events (AE),
      these untoward events may be mitigated through AE-driven algorithms. SUMMARY: AE
      driven algorithms combine effective nonpharmaceutical and pharmaceutical
      treatment modalities implemented by a multidisciplinary effort that incorporates
      nursing interventions, patient education, and referrals to pain-management
      specialists, podiatrists, and dermatologists, as appropriate. Effective AE
      prevention and management reduce the need for dose interruptions and
      modifications, allowing patients the opportunity to derive the maximal benefit
      from TKI therapy, while maintaining quality of life. CONCLUSIONS: Optimal use of
      targeted therapies in the treatment of MTC depends on careful patient selection,
      interdisciplinary communication, and patient education and encouragement to
      enhance compliance and safety, optimize consistent dosing, and maximize the use
      of effective therapies.

PMID- 24902007
TI  - Efficacy of levomilnacipran extended-release in major depressive disorder: pooled
      analysis of 5 double-blind, placebo-controlled trials.
AB  - INTRODUCTION/OBJECTIVE: Post hoc analyses were conducted to evaluate the efficacy
      of levomilnacipran extended-release (ER) in subgroups of patients with major
      depressive disorder (MDD). METHODS: Data were pooled from 5 completed Phase
      II/III studies. Patients were categorized by sex, age, MDD duration, recurrence
      of MDD, current episode duration, number of prior episodes, and baseline
      Montgomery-Asberg Depression Rating Scale (MADRS) score. Efficacy was evaluated
      by MADRS least squares (LS) mean change from baseline, response (MADRS
      improvement >=50%), and remission (MADRS <=10). RESULTS: In the pooled
      population, treatment with levomilnacipran ER versus placebo resulted in greater
      improvement in MADRS score (-15.8 versus -12.9; LS mean difference, -2.9; P <
      .001) and higher response rates (44.7% versus 34.5%; P < .001). Comparable
      treatment effects were found in most subgroups. Remission rates in the overall
      population were higher for levomilnacipran ER versus placebo (27.7% versus 21.5%;
      P < .05); notably high remission rates were seen in patients with baseline MADRS
      score < 30 (48.8% versus 28.9%; P < .001). Discussion Clinically meaningful
      improvements in depressive symptoms were found across subgroups, including
      statistically significant outcomes for both response and remission. CONCLUSION:
      Levomilnacipran ER was efficacious across a wide range of MDD patients, including
      men and women, ages 18-78, with varying histories and symptom severity.

PMID- 24902008
TI  - MicroRNAs in central nervous system development.
AB  - During early and late embryo neurodevelopment, a large number of molecules work
      together in a spatial and temporal manner to ensure the adequate formation of an
      organism. Diverse signals participate in embryo patterning and organization
      synchronized by time and space. Among the molecules that are expressed in a
      temporal and spatial manner, and that are considered essential in several
      developmental processes, are the microRNAs (miRNAs). In this review, we highlight
      some important aspects of the biogenesis and function of miRNAs as well as their
      participation in ectoderm commitment and their role in central nervous system
      (CNS) development. Instead of giving an extensive list of miRNAs involved in
      these processes, we only mention those miRNAs that are the most studied during
      the development of the CNS as well as the most likely mRNA targets for each miRNA
      and its protein functions.

PMID- 24902009
TI  - Global coagulation tests: their applicability for measuring direct factor Xa- and
      thrombin inhibition and reversal of anticoagulation by prothrombin complex
      concentrate.
AB  - BACKGROUND: Specific mass spectrometry and direct activated factor X (Xa)- and
      thrombin inhibition assays do not allow determination of the reversal of
      anticoagulant effects of non-vitamin K direct oral anticoagulants (NOACs) by
      prothrombin complex concentrate (PCC). The objective of this study was the
      evaluation of the applicability of a variety of commercially available global
      coagulation assays in analyzing the reversal of NOAC anticoagulation by PCC.
      METHODS: Plasma and whole blood were spiked with apixaban or dabigatran and PCC
      was added to these samples. Prothrombin time (PT), modified PT (mPT), activated
      partial prothrombin time (APTT), thrombography (CAT method) and
      thromboelastography (ROTEM, TEG) were performed. RESULTS: Assays triggered by
      contact activation (APTT, INTEM) did not show inhibitor reversal by PCC. Assays
      triggered by tissue factor (TF) showed NOAC type and NOAC concentration dependent
      anticoagulation reversal effects of PCC ranging from partial normalization to
      overcorrection of the following parameters: clotting or reaction time (PT, mPT
      TEG-TF, EXTEM, FIBTEM); angle in thromboelastography (TEG-TF); thrombin
      generation (CAT) lag time, endogenous thrombin potential (ETP) and peak thrombin.
      Extent of reversal was assay reagent dependent. ETP (5 pM TF) was the only
      parameter showing complete reversal of anticoagulation by PCC for all NOACs
      ranging from 200 to 800 MUg/L. CONCLUSIONS: ETP fits with the concept that
      reversal assessment of NOAC anticoagulation by PCC should be based on
      measurements on the clotting potential or thrombin generating potential of the
      plasma or whole blood patient sample. Low sensitivity of ETP for NOACs and its
      correlation with bleeding are issues that remain to be resolved.

PMID- 24902010
TI  - Multiple curve comparisons with an application to the formation of the dorsal
      funiculus of mutant mice.
AB  - Much biological experimental data are represented as curves, including
      measurements of growth, hormone, or enzyme levels, and physical structures. Here
      we consider the multiple testing problem of comparing two or more nonlinear
      curves. We model smooth curves of unknown form nonparametrically using penalized
      splines. We use random effects to model subject-specific deviations from the
      group-level curve. We present an approach that allows examination of overall
      differences between the curves of multiple groups and detection of sections in
      which the curves differ. Adjusted p-values for each single comparison can be
      obtained by exploiting the connection between semiparametric mixed models and
      linear mixed models and employing an approach for multiple testing in general
      parametric models. In simulations, we show that the probability of false-positive
      findings of differences between any two curves in at least one position can be
      controlled by a pre-specified error level. We apply our method to compare curves
      describing the form of the mouse dorsal funiculus - a morphological curved
      structure in the spinal cord - in mice wild-type for the gene encoding EphA4 or
      heterozygous with one of two mutations in the gene.

PMID- 24902011
TI  - Investigating the effect of Phlomis lanceolata Boiss and hohen on cancer cell
      lines.
AB  - Phlomis lanceolata is a medicinal plant that has long been used to treat various
      conditions such as diabetes, gastric ulcer, hemorrhoids, inflammation and wounds.
      As most of Phlomis species have shown cytotoxic activity against proliferation of
      different cell lines, a biological investigation of P. lanceolata was carried out
      in this study. The aim of this study was to find out the in vitro cytotoxic
      activity of total extract and different fractions of Phlomis lanceolata on four
      cell lines. Cytotoxic activity of the metanolic total extract and partition
      fractions of chloroform, ethyl acetate and petroleum ether of flowering aerial
      parts of Phlomis lanceolata on the HT29, Caco2, T47D and NIH3T3 cell lines is
      examined by MTT. Petroleum ether fraction showed high cytotoxic activity against
      proliferation of all four cell lines. Presence of heavy triterpens and lipophil
      compounds recognized by TLC test in Petroleum ether fraction is responsible for
      high cytotoxic activity. The results emphasize the importance of phytochemical
      studies which could lead to the discovery of new active compounds.

PMID- 24902012
TI  - Neonatal bacteriemia isolates and their antibiotic resistance pattern in neonatal
      insensitive care unit (NICU) at Beasat Hospital, Sanandaj, Iran.
AB  - Bacteremia continues to result in significant morbidity and mortality,
      particularly among neonates. There is scarce data on neonatal bacteremia in among
      Iranian neonates. In this study, we determined neonatal bacteremia isolates and
      their antibiotic resistance pattern in neonatal insensitive care unit at Beasat
      hospital, Sanandaj, Iran. During one year, all neonates admitted to the NICU were
      evaluated. Staphylococcal isolates were subjected to determine the prevalence of
      MRS and mecA gene. A total of 355 blood cultures from suspected cases of sepsis
      were processed, of which 27 (7.6%) were positive for bacterial growth. Of the 27
      isolates, 20 (74%) were Staphylococcus spp as the leading cause of bacteremia.
      The incidence of Gram negative bacteria was 04 (14.8%). The isolated bacteria
      were resistant to commonly used antibiotics. Maximum resistance among
      Staphylococcus spp was against Penicillin, and Ampicillin. In our study, the
      isolated bacteria were 7.5 % Vancomycin and Ciprofloxacin sensitive. Oxacillin
      disk diffusion and PCR screened 35% and 30% mec a positive Staphylococcus spp.
      The spectrum of neonatal bacteremia as seen in NICU at Beasat hospital confirmed
      the importance of pathogens such as Staphylococcus spp. Penicillin, Ampicillin
      and Cotrimoxazol resistance was high in theses isolates with high mecA gene
      carriage, probably due to antibiotic selection.

PMID- 24902013
TI  - Histopathologic and sonographic analysis of laparoscopic removal ovarian
      nonendometriotic cyst: the evaluating effects on ovarian reserve.
AB  - Currently, laparoscopic cystectomy is the first-line therapy for ovarian benign
      cysts that are resistant to current therapies. There are different studies that
      point to ovarian reserve damage due to laparoscopic cystectomy. In this study, we
      evaluate the ovarian damage following laparoscopic cystectomy for non
      endometriosis cysts using ultrasound and pathology findings. This is a
      prospective cohort study conducted between 7 rd month of 2011 and 10th month of
      2012 in Women hospital affiliated to Tehran university of medical sciences.45 non
      endometriosis cysts (17 teratoma,7 mucinous, 10 simple serous and 11 simple
      cysts) underwent laparoscopic cystectomy with stripping technique. Amount of
      excised parenchyma, number of lost oocytes and cyst wall fibrosis thickness were
      histopathologically studied. Before and 3 months after surgery antral follicle
      count was evaluated by ultrasound. AFC after cystectomy for teratoma and simple
      serous was significantly reduced P<0.05. By larger teratomas and more parenchyma
      inadvertently removed during their excision (1.64, 0.255) reduced AFC was seen
      and in simple serous cysts with more removed parenchyma amount (1.5) reduced AFC
      occurred. In our study simple cysts excision led to a loss in AFC that was not
      associated with any other cyst parameters. Mucinous cysts resection led to no
      specific ovarian reserve damage. Laparoscopic cystectomy for non-endometriosis
      leads to reduced ovarian reserve.

PMID- 24902014
TI  - The relationship between QT dispersion and ischemic injuries in myocardial
      isotope scan.
AB  - The relationship between QT dispersion and myocardial ischemia is still
      controversial. Therefore, we aimed to investigate the relationship between QTd
      and the severity and extent of myocardial ischemia. In this cross-sectional
      study, 141 patients having symptoms of CAD who referred to our medical center
      during 2009-2010, and were examined with myocardial isotope scan and ECG, were
      enrolled. Based on the Electrocardiography and Single-Photon Emission Computed
      Tomography results, the patients were categorized as having normal, mild,
      moderate, and severe ischemia. QTd was measured at rest and under stress as the
      maximum difference between QT intervals in 12-lead ECG. Ultimately, the
      correlation between rest and stress QTd and the severity and extent of ischemia
      (number of ischemic segments and summed ischemic score) were investigated, and
      the rest and stress QTd was compared between the groups. QTd under stress was
      positively correlated with the number of ischemic segments and summed ischemic
      scores in all patients. In normal patients, stress and rest QTd were the same.
      The QTd under stress significantly increased in patients with ischemia. There was
      no significant difference between the groups regarding QTd at rest. Stress QTd
      was significantly greater in patients with severe ischemia and greater in
      patients with mild and moderate ischemia compared with the normal patients.
      Stress QTd difference between mild and moderate ischemic groups was not
      significant. QTd under stress is related to the severity and extent of myocardial
      ischemia and is clinically useful for identifying ischemic myocardial injuries.

PMID- 24902015
TI  - Association of polymorphisms at LDLR locus with coronary artery disease
      independently from lipid profile.
AB  - Coronary artery disease (CAD) is the leading cause of mortality in many parts of
      the world. Genome-wide association studies (GWAS) have identified several genetic
      variants associated with CAD in Low-density lipoprotein receptor (LDLR) locus.
      This study was evaluated the possible association of genetic markers at LDLR
      locus with CAD irrespective to lipid profile and as well as the association of
      these SNPs with severity of CAD in Iranian population. Sequencing of 2 exons in
      LDLR gene (Exon 2, 12) and part of intron 30 of SMARCA4 gene include rs1122608,
      was performed in 170 Iranian patients angiographically confirmed CAD and 104
      healthy controls by direct sequencing. Sullivan's scoring system was used for
      determining the severity of CAD in cases. Our results showed that homozygote
      genotypes of rs1122608 (P<0.0001), rs4300767 (P<0.005) and rs10417578 (p<0.007)
      SNPs have strong protective effects on the CAD. In addition, we found that
      rs1122608 (GT or TT) was at higher risk of three vessel involvement compared to
      single vessels affecting (P=0.01).

PMID- 24902016
TI  - Discriminant of validity the Wender Utah rating scale in Iranian adults.
AB  - The aim of this study is the normalization of the Wender Utah rating scale which
      is used to detect adults with Attention-Deficit and Hyperactivity Disorder
      (ADHD). Available sampling method was used to choose 400 parents of children (200
      parents of children with ADHD as compared to 200 parents of normal children).
      Wender Utah rating scale, which has been designed to diagnose ADHD in adults, is
      filled out by each of the parents to most accurately diagnose of ADHD in parents.
      Wender Utah rating scale was divided into 6 sub scales which consist of
      dysthymia, oppositional defiant disorder; school work problems, conduct disorder,
      anxiety, and ADHD were analyzed with exploratory factor analysis method. The
      value of (Kaiser-Meyer-Olkin) KMO was 86.5% for dysthymia, 86.9% for oppositional
      defiant disorder, 77.5% for school related problems, 90.9% for conduct disorder,
      79.6% for anxiety and 93.5% for Attention deficit/hyperactivity disorder, also
      the chi square value based on Bartlett's Test was 2242.947 for dysthymia,
      2239.112 for oppositional defiant disorder, 1221.917 for school work problems,
      5031.511 for conduct, 1421.1 for anxiety, and 7644.122 for ADHD. Since mentioned
      values were larger than the chi square critical values (P<0.05), it found that
      the factor correlation matrix is appropriate for factor analysis. Based on the
      findings, we can conclude that Wender Utah rating scale can be appropriately used
      for predicting dysthymia, oppositional defiant disorder, school work problems,
      conduct disorder, anxiety, in adults with ADHD.

PMID- 24902017
TI  - Inter-observer reproducibility before and after web-based education in the
      Gleason grading of the prostate adenocarcinoma among the Iranian pathologists.
AB  - This study was aimed at determining intra and inter-observer concordance rates in
      the Gleason scoring of prostatic adenocarcinoma, before and after a web-based
      educational course. In this self-controlled study, 150 tissue samples of
      prostatic adenocarcinoma are re-examined to be scored according to the Gleason
      scoring system. Then all pathologists attend a free web-based course. Afterwards,
      the same 150 samples [with different codes compared to the previous ones] are
      distributed differently among the pathologists to be assigned Gleason scores.
      After gathering the data, the concordance rate in the first and second reports of
      pathologists is determined. In the pre web-education, the mean kappa value of
      Interobserver agreement was 0.25 [fair agreement]. Post web-education
      significantly improved with the mean kappa value of 0.52 [moderate agreement].
      Using weighted kappa values, significant improvement was observed in inter
      observer agreement in higher scores of Gleason grade; Score 10 was achieved for
      the mean kappa value in post web-education was 0.68 [substantial agreement]
      compared to 0.25 (fair agreement) in pre web-education. Web-based training
      courses are attractive to pathologists as they do not need to spend much time and
      money. Therefore, such training courses are strongly recommended for significant
      pathological issues including the grading of the prostate adenocarcinoma. Through
      web-based education, pathologists can exchange views and contribute to the rise
      in the level of reproducibility. Such programs need to be included in post
      graduation programs.

PMID- 24902018
TI  - Temporary abdominal closure in the critically ill patients with an open abdomen.
AB  - The emergent abdominal surgeries from either of traumatic or non traumatic causes
      can result in situations in which the abdominal wall cannot initially be closed.
      Many techniques have been reported for temporary coverage of the exposed viscera,
      but the result of various techniques remains unclear. During 94 months, 19
      critically ill patients whit an open abdomen underwent surgery using plastic bags
      (Bogota bag). The study population comprised of 11 (57.9%) male and 8 (42.1%)
      female with an average age of 32.26+14.8 years. The main indications for
      temporary abdominal coverage were as follows: planned reoperation in 11 (57.9%)
      patients, subjective judgment that the fascia closure is too tight in 6 (31.6%)
      patient's damage control surgery in one patient (5.3%) and development of
      abdominal compartment surgery in one patient (5.3%). Surgical conditions
      requiring temporary abdominal closure was severe post operative peritonitis in 9
      (47.4%) patients, post operative intestinal fistula in 4 (21.1%) patients, post
      traumatic intra abdominal bleeding in 3 (15.8%) patients and intestinal
      obstructions in 3 (15.8%) patients. Length of hospitalization was 45+23.25 days
      and the mean total number of laparotomies was 6.2+3.75 times per patient. Three
      bowel fistulas occurred due to a missed injury at the time of initial operation
      that was discovered during changing the plastic sheet. They were unrelated to
      coverage technique. All of them were treated by repair of the defect and serosal
      patch by adjacent bowel loop. Only one (10.0%) patient underwent definitive
      closure within 6 months of initial operation. The remaining survivor has declined
      to have hernia repaired. There were 4 (%21.1) early postoperative deaths that
      were not related to the abdominal coverage technique. Also, there were 5 (26.3%)
      late deaths that were due to dissemination of malignancy with a mean survival
      time of 20.8+13 (range 2-54) months. Currently 10 patients (52.6%) are alive at a
      follow up of 45 (range 1-94) months. Only one (10.0%) patient underwent
      definitive closure within 6 months of initial operation. The remaining survivor
      has declined to have hernia repaired. Bogota bag technique is a rapid, simple and
      inexpensive technique for temporary abdominal coverage.

PMID- 24902019
TI  - Demographic and histopathologic study of Kaposi's sarcoma in a dermatology clinic
      in the years of 2006 to 2011.
AB  - Kaposi's sarcoma is a low-grade vascular tumor that its prevalence is increasing
      all around the world due to the increasing prevalence of HIV and organ
      transplantations. In this study, we assessed risk factors of Kaposi's sarcoma
      among Iranian patients were referred to Dermatopathology Department of Razi
      Hospital of Tehran University of Medical Sciences between the years of 2006 to
      2011. Also, disease stages have been assessed on pathologic specimens. Thirty
      four patients diagnosed with Kaposi's sarcoma entered the study. Of the 34
      patients, 29% were female, and 71% were male, mean age was 66 years and average
      disease duration was 6 months. The most common patient's pathologic stages were
      reported: patch 32%, patch to plaque 24%, plaque 12%. The most prevalent location
      of involvement was lower extremity (88%), and upper extremity was involved in
      24%. At presentation time, the mean number of lesions was 3 to 4. 15% of patients
      had a history of smoking and 15% had a history of immunosuppressive drugs. HIV
      infection did not observe in the patients. Based on the present study, Kaposi's
      sarcoma is a disease of elderly and is higher in older men. The most common site
      of Kaposi's sarcoma involvement is lower extremity, and the most common
      pathologic stage was the patch to plaque.

PMID- 24902020
TI  - Gestational diabetes mellitus and iron supplement; effects on pregnancy outcome.
AB  - The possible effect of iron supplementation has been investigated in the normal
      population and patients with gestational diabetes mellitus (GDM). In this study,
      we survey the risk factors of GDM in pregnant women in contrast with
      normoglycemic patients in a case control study in patients using iron supplement.
      This case control study conducted on 52 pregnant women with GDM (25 women with
      type Al and 27 women with Type A2 of GDM). The control group randomly selected 50
      normoglycemic women. Venous blood sampling was done between 24 and 28 weeks of
      pregnancy for measuring of ferritin, lipoproteins, uric acid and malondialdehyde
      serum levels. Under study variables including age, gestational age, weight and
      BMI were gathered. All the women were followed up until the time of delivery and
      pregnancy outcome were gathered. The serum ferritin levels in GDM group was
      31.22+15.44, which is significantly higher than 24.76+8.94, in the control group
      with (P=0.012). Plasma hemogulobin in the control group was 12.2+0.1 compared to
      12.9+0.1 in GDM group which was significantly lower (P=0.005). Triglycerides was
      significantly higher in GDM group in contrast with the control group,
      275.08+143.17 and 192.30+92.13 (P=0.001), respectively. Finally, our findings
      indicate the concentration of serum ferritin levels was significantly higher in
      The GDM group.

PMID- 24902021
TI  - Quality of life of medical students in Tehran University of Medical Sciences.
AB  - This study aims to investigate the quality of life (QOL) of Tehran University of
      Medical Sciences' (TUMS) medical students at different educational levels and
      specify the most important factors related to this quality. A sample of 242
      medical students was selected randomly, given their number in three educational
      levels (basic sciences, physiopathology-stager and intern). The QOL was measured
      by WHOQOL-BREF. The students obtained average high score in two psychological and
      environmental health domains, and low score in physical health and social
      relationship domains. As the educational level of students increased their
      quality of life decreased at all four domains. At social relationship domain, the
      female students had overall better situation as compared to males (p=0.009). The
      female and male students had opposite condition at the level of basic sciences
      and internship, in a way that the female students earned higher marks at basic
      sciences level and the males at internship level (P= 0.008). The condition of
      female students in terms of environmental, physical and psychological health
      became static while their education rose. However, only environmental health of
      the male students reduced as their education level increased (P= 0.05). The
      students were of undesirable conditions in two domains of social relationship and
      physical health. Internship is a specific level in both groups which has a
      negative impact on the dimensions of quality of life and naturally needs more
      care for the students. Married status improved the students' QOL and could
      moderate the undesired effects of internship.

PMID- 24902022
TI  - Relationship between unexplained arthralgia and vitamin D deficiency: a case
      control study.
AB  - Arthralgia is a common presenting symptom of many rheumatic diseases. Vitamin D
      deficiency may lead to progression of skeletal symptoms to definite disease in
      susceptible subjects. This study was conducted to determine the relationship
      between vitamin D deficiency and unexplained arthralgia. Patients with arthralgia
      not related to a definite clinical condition were selected prospectively among
      subjects presented to a rheumatology clinic. Serum 25-hydroxyvitamin D (25-OHD)
      was measured by ELISA method and levels less than 20 ng/ml were considered as
      deficient levels. Serum 25-OHD levels and proportion of 25-OHD deficiency was
      compared in patients versus control. The association of serum 25-OHD and
      arthralgia was assessed by calculation of odds ratio (OR) using regression
      analysis. 167 patients with mean age of 38 +/- 13.3 and 283 controls with mean
      age of 42.6+/-14.37 years (P=0.001) were studied. In patients mean serum 25-OHD
      was lower and proportion of deficiency was higher (P=0.001 for both).Serum 25-OHD
      deficiency was associated with 3.01 times increased risk of arthralgia (OR=3.01,
      95% CI, 2.0- 4.25, P=0.001). After adjusment for age and sex, the risk of
      arthralgia remained significan at OR= 2.71(95%CI, 1.79-4.11,P=0.001).The odds of
      arthralgia decreased with increasing serum 25-OHD from OR=3.48 (95% CI,197
      6,P=0.001) at serum <10 ng/ml to 3.39 (95%CI,1.93-5.98, P=0.001) at 10-19.9; and
      1.31 (95%CI, 0.69-2.5, P=0.42) at 20-29.9 ng/ml. These findings indicate
      significant association of vitamin D deficiency and arthralgia. Regarding vitamin
      D deficiency as an environmental factor for development or progression of
      rheumatic diseases, this study justifies identification and correction of vitamin
      D deficiency in patients with arthralgia.

PMID- 24902023
TI  - Post graduate ESP curriculum: reading and writing needs.
AB  - Assessing learners' needs is an integral part of any curriculum and course design
      , namely English for specific purposes (ESP), syllabus design, materials
      development, teaching methods and testing issues. Critical approach to needs
      analysis, which is a relatively recent approach, acknowledges the rights of
      different stakeholders including teachers, students and administrators in the
      process of needs analysis. However, there has been no formal need analysis for
      syllabus design at postgraduate level in Medical Universities affiliated to the
      Ministry of Health in Iran. This study, conducted in 2011, was an attempt to
      assess the reading and writing needs of postgraduate students in ESP courses on
      the basis of critical approach to needs analysis. The study population consisted
      of 67 people: 56 postgraduate students, 5 heads of departments, 5 ESP instructors
      and 1 executive manager at the Ministry of Health in Iran. Ethical and
      demographic forms, needs analysis questionnaires, and a form of semi-structured
      interview were the instruments of the study. According to the findings, there was
      a discrepancy between students' and instructors' perception of learners' needs
      and the assumed needs appearing in the syllabi prescribed by the Ministry of
      Health in Iran. This study showed that a call for critical needs analysis in
      which the rights of different stakeholders are acknowledged is necessary for
      meeting the requirements of any ESP classes especially at postgraduate level
      where the instructors and learners are fully aware of learners' needs.

PMID- 24902024
TI  - An unusual case of recurrent gastric cancer long after the first gastrectomy due
      to adenocarcinoma.
AB  - The postgastrectomy recurrence rate is as high as 30-65%, with 5-year overall
      survival rates of <20%. Local recurrence is very common which occurs in 38-45% of
      cases. The most common sites of locoregional recurrence are the gastric remnant
      at the anastomosis, the gastric bed, and the regional nodes. The recurrence may
      occur as early and late events after gastrectomy. Most recurrences are early,
      within three years of surgery. Numerous studies reported the late recurrences,
      but most of them having a survival time of less than ten years. This report
      elucidates a case of recurrent gastric cancer after 24 years postoperatively.

PMID- 24902025
TI  - Arterial glomerulus at the hilum of the right kidney and the abnormal course of
      the right testicular artery: a case report.
AB  - Variations in the origin of arteries in the abdomen are very common. With the
      invention of new operative techniques within the abdomen cavity, the anatomy of
      abdominal vessels has assumed a great deal of clinical importance. We report here
      a rare case of formation of an "arterial glomerulus" at the hilum of the right
      kidney by the branches of right renal artery. There were 2 renal veins; a
      superficial and a deep. The deep vein had a peculiar course through the arterial
      glomerulus. The right testicular vein drained into the deep renal vein. We also
      observed a variant origin and course of right testicular artery. Prior knowledge
      of unusual branching pattern of renal vessels is necessary in the surgical
      interventions which require hilar dissection. Similarly, abnormal origin or
      course of testicular artery becomes apparent during surgical procedures like
      varicocele and undescended testes. Therefore, knowledge of such an anomaly in the
      testicular artery helps to avoid iatrogenic injuries during radiological or
      surgical procedures.

PMID- 24902026
TI  - Medical education: how does it flourish as a scientific discipline?

PMID- 24902027
TI  - Insensible is a novel nuclear inhibitor of Notch activity in Drosophila.
AB  - Notch signalling regulates a wide range of developmental processes. In the
      Drosophila peripheral nervous system, Notch regulates a series of binary fate
      decisions that lead to the formation of regularly spaced sensory organs. Each
      sensory organ is generated by single sensory organ precursor cell (SOP) via a
      series of asymmetric cell divisions. Starting from a SOP-specific Cis-Regulatory
      Module (CRM), we identified insensible (insb), a.k.a CG6520, as a SOP/neuron
      specific gene encoding a nuclear factor that inhibits Notch signalling activity.
      First, over-expression of Insb led to the transcriptional repression of a Notch
      reporter and to phenotypes associated with the inhibition of Notch. Second, while
      the complete loss of insb activity had no significant phenotype, it enhanced the
      bristle phenotype associated with reduced levels of Hairless, a nuclear protein
      acting as a co-repressor for Suppressor of Hairless. In conclusion, our work
      identified Insb as a novel SOP/neuron-specific nuclear inhibitor of Notch
      activity in Drosophila. 

PMID- 24902028
TI  - A meta-analysis of randomized controlled trials of low-volume polyethylene glycol
      plus ascorbic acid versus standard-volume polyethylene glycol solution as bowel
      preparations for colonoscopy.
AB  - BACKGROUND: Standard-volume polyethylene glycol (PEG) gut lavage solutions are
      safe and effective, but they require the consumption of large volumes of fluid. A
      new lower-volume solution of PEG plus ascorbic acid has been used recently as a
      preparation for colonoscopy. AIM: A meta-analysis was performed to compare the
      performance of low-volume PEG plus ascorbic acid with standard-volume PEG as
      bowel preparation for colonoscopy. STUDY: Electronic and manual searches were
      performed to identify randomized controlled trials (RCTs) that compared the
      performance of low-volume PEG plus ascorbic acid with standard-volume PEG as
      bowel preparation for colonoscopy. After a methodological quality assessment and
      data extraction, the pooled estimates of bowel preparation efficacy during bowel
      cleansing, compliance with preparation, willingness to repeat the same
      preparation, and the side effects were calculated. We calculated pooled estimates
      of odds ratios (OR) by fixed- and/or random-effects models. We also assessed
      heterogeneity among studies and the publication bias. RESULTS: Eleven RCTs were
      identified for analysis. The pooled OR for preparation efficacy during bowel
      cleansing and for compliance with preparation for low-volume PEG plus ascorbic
      acid were 1.08 (95% CI = 0.98-1.28, P = 0.34) and 2.23 (95% CI = 1.67-2.98,
      P<0.00001), respectively, compared with those for standard-volume PEG. The side
      effects of vomiting and nausea for low-volume PEG plus ascorbic acid were reduced
      relative to standard-volume PEG. There was no significant publication bias,
      according to a funnel plot. CONCLUSIONS: Low-volume PEG plus ascorbic acid gut
      lavage achieved non-inferior efficacy for bowel cleansing, is more acceptable to
      patients, and has fewer side effects than standard-volume PEG as a bowel
      preparation method for colonoscopy.

PMID- 24902029
TI  - Bioengineered heparin: is there a future for this form of the successful
      therapeutic?
AB  - Heparin is a widely used drug for the control of blood coagulation. The majority
      of heparin that is produced commercially is derived from animal sources, is poly
      disperse in nature and therefore ill-defined in structure. This makes regulation
      of heparin challenging with respect to identifying its absolute structural
      identity, purity, and efficacy. This raises the question as to whether there
      might be alternative methods of producing commercial grade heparin. The
      commentary highlights ways that we might manufacture heparin using bioengineering
      approaches to yield a successful therapeutic replacement for animal-derived
      heparin in the future. 

PMID- 24902030
TI  - Easy identification of leishmania species by mass spectrometry.
AB  - BACKGROUND: Cutaneous leishmaniasis is caused by several Leishmania species that
      are associated with variable outcomes before and after therapy. Optimal treatment
      decision is based on an accurate identification of the infecting species but
      current methods to type Leishmania isolates are relatively complex and/or slow.
      Therefore, the initial treatment decision is generally presumptive, the infecting
      species being suspected on epidemiological and clinical grounds. A simple method
      to type cultured isolates would facilitate disease management. METHODOLOGY: We
      analyzed MALDI-TOF spectra of promastigote pellets from 46 strains cultured in
      monophasic medium, including 20 short-term cultured isolates from French
      travelers (19 with CL, 1 with VL). As per routine procedure, clinical isolates
      were analyzed in parallel with Multilocus Sequence Typing (MLST) at the National
      Reference Center for Leishmania. PRINCIPAL FINDINGS: Automatic dendrogram
      analysis generated a classification of isolates consistent with reference
      determination of species based on MLST or hsp70 sequencing. A minute analysis of
      spectra based on a very simple, database-independent analysis of spectra based on
      the algorithm showed that the mutually exclusive presence of two pairs of peaks
      discriminated isolates considered by reference methods to belong either to the
      Viannia or Leishmania subgenus, and that within each subgenus presence or absence
      of a few peaks allowed discrimination to species complexes level.
      CONCLUSIONS/SIGNIFICANCE: Analysis of cultured Leishmania isolates using mass
      spectrometry allows a rapid and simple classification to the species complex
      level consistent with reference methods, a potentially useful method to guide
      treatment decision in patients with cutaneous leishmaniasis.

PMID- 24902031
TI  - Synthesis of 5-epi-taiwaniaquinone G.
AB  - A concise synthetic approach to the unnatural 5-epi-taiwaniaquinone G has been
      developed via a Lewis acid catalyzed tandem acylation-Nazarov cyclization
      reaction to construct the tricyclic skeleton, followed by installation of the
      isopropyl group through a strategy involving coumarin formation and its
      subsequent hydrolysis. 

PMID- 24902032
TI  - Impact of bowel preparation on surveillance colonoscopy interval.
AB  - BACKGROUND/AIMS: Atpresent there are no guidelines for colonoscopy surveillance
      interval in subjects with unsatisfactory bowel preparation. Study was designed to
      compare outcomes of repeat colonoscopy at different surveillance intervals in
      patients with unsatisfactory preparation on index exam. METHODS: Ten thousand
      nine hundred and eight colonoscopies were done during the study period. Patients
      with index colonoscopy exam complete up to cecum but suboptimal bowel prep were
      included. RESULTS: Two hundred and ninety-seven patients met the inclusion
      criteria. The interval for repeat colonoscopy was <1 year in 38.5%, 1-2 years in
      33.3%, 2-3 years in 16.7%, and 3-5 years in 11.5% subjects. Adenoma detection
      rate (ADR) was 24%, high-risk adenoma detection rate (HR-ADR) was 8.4%, and
      colorectal cancer detection rate was 1.7%. The HR-ADR based on surveillance
      intervals <1 year, 1-2 years, 2-3 years, and 3-5 years was 8%, 7.9%, 2%, and
      19.4%, respectively. The HR-ADR was significantly higher at surveillance interval
      3-5 years (p < 0.05). CONCLUSION: Colonoscopies repeated at interval >3 years
      showed a significant HR-ADR. The study indicates that a surveillance interval of
      3 years can be reasonable for subjects having an index colonoscopy with
      suboptimal/fair/poor bowel prep and complete colon examination. Colonoscopy
      should be repeated earlier if symptoms develop.

PMID- 24902033
TI  - Sexual discourses and strategies among minority ethnic youth in the Netherlands.
AB  - This study explores the way minority ethnic youth in the Netherlands evaluate
      their sexual experiences, how they frame these experiences in different sexual
      discourses and how they deal with conflicts between different sexual discourses,
      both at home and in Dutch society. During 46 narrative interviews, Dutch young
      people (aged 12-22 years) from different minority ethnic communities shared their
      sexual histories and their dreams for the future relating to love and sexuality.
      Different sexual discourses can be identified in the language they used to
      describe their ideas and their experiences. Young people grow up with a variety
      of discourses but actively re-shape them according to circumstances and need. In
      many cases, young people experience a conflict between the discourses of the home
      and those that are prevalent more generally in Dutch society. Young people's ways
      of negotiating these contradictory discourses comprise four main strategies: (1)
      conforming to parents' values, (2) breaking up with parents, (3) leading a double
      life and (4) integrating competing discourses. By bringing together different
      sexual discourses and acknowledging diverse strategies, sexual health policies
      can become more effective in promoting sexual health for minority ethnic youth.
      Findings from the study add fuel to debate on understanding (sexual) agency among
      young people, exhibiting the social 'embeddedness' of individual agency. 

PMID- 24902034
TI  - Patients' quality of life and role of the ambulatory in after-surgery stoma care.
      A single center experience.
AB  - AIM: The aim is to assess on which aspects of everyday-life the post surgery
      stoma-care ambulatory should physically and psychologically assist the patients.
      MATERIAL OF STUDY: Seventy patients (33 male, 37 female, mean age 68 years)
      accepted to fill-in the Stoma-QoL questionnaire from January to December 2011.
      The questionnaire consists of 20 questions addressing different possible
      discomforts of everyday life. RESULTS: Our results demonstrate that patients with
      temporary ileostomy have a mean score of quality of life index of 63. Patients
      with ileostomy demonstrated a higher quality of life score compared to patients
      with colostomy. DISCUSSION: Our results confirmed that patients with ileostomy
      have a better perception of quality of life compared to patients with colostomy.
      Moreover, our data clearly show that patients are more concerned on stoma
      management compared to the hypothetical prejudice of society. CONCLUSIONS: The
      stoma care ambulatory have a crucial role, offering to the patient and his/her
      family an adequate psychological support, and teaching the management of the
      stoma and the pouch.

PMID- 24902035
TI  - Improved electrochemical detection of a transthyretin synthetic peptide in the
      nanomolar range with a two-electrode system integrated in a glass/PDMS microchip.
AB  - An alternative to a three-electrode set-up for electrochemical detection and
      analysis in microfluidic chips is described here. The design of the
      electrochemical sensor consists of the surface of the glass substrate covered
      with a PDMS block which bears the microfluidic channels. A band microelectrode
      which acts as a working electrode surrounded by a large counter electrode is
      obtained at the micrometric level to propose a simple and efficient sensing area
      for on-a-chip analysis. The counter-electrode with a surface area about 22-fold
      greater than the working-microelectrode can also be considered as a pseudo
      reference since its current density is low and thus limits the potential
      variations around the rest potential. To this purpose, the [Fe(III)(CN)6]3
      /[Fe(II)(CN)6]4- redox couple was used in order to set a reference potential at 0
      V since both electrodes were platinum. The electrochemical microchip performance
      was characterized using differential pulse voltammetric (DPV) detection and
      quantification of the optically multi-labelled transthyretin synthetic peptide
      mimicking a tryptic fragment of interest for the diagnosis of familial
      transthyretin amyloidosis (ATTR). The limit of detection of the peptide by the
      working microelectrode was 25 nM, a value 100-fold lower than the one reported
      with conventional capillary electrophoresis coupled with laser-induced
      fluorescence under the same analytical conditions.

PMID- 24902036
TI  - Ketoxime coupling of p-acetylphenylalanine at neutral pH for site-directed spin
      labeling of human sulfite oxidase.
AB  - Site-directed spin labeling of the unnatural amino acid p-acetylphenylalanine (p
      AcPhe) using oxime based coupling chemistry is successfully applied to
      investigate human sulfite oxidase (hSO), a protein containing an essential
      cysteine residue, which impedes the use of thiol based coupling chemistry. The
      protein was found to be sensitive toward typical reaction conditions of oxime
      coupling, namely, acidic reaction conditions and elevated temperatures. Thus,
      coupling at neutral pH and room temperature is mandatory. Three catalysts
      described in the literature to accelerate the reaction rate have been tested.
      Best spin labeling efficiencies were observed for p-methoxyaniline, while the
      other catalysts described in the literature to have even better performance for
      oxime coupling at neutral pH were substantially less active or led to
      precipitation of the protein. A clear correlation of spin labeling efficiency
      with the local environment of the residue is found, shedding some light on the
      importance of the sterically demanding reaction complex between p-AcPhe, the
      aniline catalyst, and the spin label for the reaction rate. The analysis of the
      line shape has shown that its interpretation in terms of local environment is
      more challenging as compared to the well-established spin labels based on
      cysteine chemistry. To this end the results presented here indicate that the
      larger steric demand of the spin labeled p-AcPhe can induce structural effects
      instead of reporting on them. 

PMID- 24902037
TI  - Therapy of inflammatory bowel disease: what to expect in the next decade.
AB  - PURPOSE OF REVIEW: The increased understanding of the molecular mechanisms that
      are responsible for inflammatory bowel disease (IBD) has led to a wide range of
      potential therapeutic targets for this condition. Physicians treating individuals
      with Crohn's disease and ulcerative colitis have a growing armamentarium of
      options to choose from in managing these patients. This article aims to summarize
      the relevant literature in the area of emerging therapy in IBD. RECENT FINDINGS:
      The widespread use of antitumor necrosis factor medications brought a landmark
      change in the treatment of IBD. More recently, several drugs have been shown to
      provide benefit in IBD in phase III studies by blocking other antiinflammatory
      pathways. The most likely new medications that will be available include
      vedolizumab for ulcerative colitis and ustekinumab for Crohn's disease, which
      target cellular adhesion and inflammatory cell signaling, respectively. Other
      promising drugs focus on blockade of Janus kinase, inhibition of various
      chemokines, and biologic therapy such as hematopoietic stem cell transplants and
      mesenchymal cell infusions. SUMMARY: The growing understanding of the
      pathogenesis of IBD has led to new molecular targets for therapy. Over the next
      decade, the number of treatments available will grow, targeting cellular
      adhesion, protein regulation, inflammatory signal pathways, and immune tolerance.

PMID- 24902039
TI  - Surveillance of hantaviruses in Poland: a study of animal reservoirs and human
      hantavirus disease in Subcarpathia.
AB  - The first cluster of hemorrhagic fever with renal syndrome (HFRS) in Poland was
      identified in 2007 in the Subcarpathian region. The natural environment of this
      area is a key habitat for hantavirus vectors. The animal reservoir of existing
      human HFRS clusters was studied to assess the occurrence of viruses (including
      Tula virus, Puumala virus, and Dobrava-Belgrade virus) among rodents. We examined
      70 suspected human cases with symptoms corresponding to the clinical picture of
      HFRS. Serological analysis (indirect immunofluorescence assay and immunoblot)
      confirmed the presence of anti-hantavirus antibodies in 18 patients, which were
      surveyed with regard to developed symptoms and presumed rodent contact.
      Seroepidemiological analysis of newly confirmed human cases was performed,
      putative areas of human exposure were studied, and 194 rodents were subsequently
      captured from identified areas. Internal organs (lungs, heart, spleen, bladder,
      and kidneys) were collected from 64 Apodemus flavicollis, 55 Apodemus agrarius,
      40 Myodes glareolus, 21 Mus musculus, and 14 Microtus arvalis and tested for the
      presence of hantavirus RNA by reverse transcription and subsequent real-time PCR.
      Positive samples were also tested by indirect immunofluorescence. Animal
      reservoir surveillance enabled the first detection of Puumala virus and Dobrava
      Belgrade virus among animals in Poland. Furthermore, some places where rodents
      were captured correlated with areas of residence of laboratory-confirmed human
      cases and likely detected virus species. Moreover, three species of hantaviruses
      coexisting in a relatively small area were identified.

PMID- 24902040
TI  - The short-term impact of peers as co-facilitators of an HIV prevention programme
      for adolescents: a cluster randomised controlled trial.
AB  - BACKGROUND: There is no consensus concerning the most effective type of
      facilitator to promote healthy sexual behaviours in interventions targeting
      adolescents. OBJECTIVES: To evaluate the facilitator's effect on the
      implementation of the COMPAS programme (Spanish acronym for Skills for
      Adolescents with Healthy Sexuality), a school-based HIV prevention protocol.
      METHODS: Participants were 832 Spanish scholars aged 14 to 18. Fifteen schools
      were randomly assigned to one of the three following schemes: COMPAS delivered by
      experts only; the same programme administered by experts and peers; or a control
      group, not exposed to any intervention. RESULTS: The experts achieved an
      improvement in HIV knowledge and attitudes towards HIV and condom use; however,
      experts associated to peers only succeeded in increasing HIV knowledge. The
      effect size of the changes indicated a greater positive change in the programme
      when applied by experts than by experts and peers. CONCLUSIONS: The participation
      of peers as co-facilitators did not increase the efficacy of a programme
      delivered by experts to Spanish adolescents. Education delivered by experts was
      the most effective modality for reducing sexual risk. COMPAS is the only Spanish
      programme targeting the promotion of safer sex behaviours in adolescents whose
      efficacy has been evaluated with different health agents in Spain.

PMID- 24902042
TI  - A computer-based screening method for distress in patients with multiple
      sclerosis: a feasibility study.
AB  - BACKGROUND: In multiple sclerosis (MS) patients, symptoms of anxiety, depression,
      pain, and cognitive impairment are highly prevalent and contribute to lower
      wellbeing. As these physical and psychological symptoms of distress often stay
      unnoticed, regular screening could offer possibilities to identify and refer
      impaired patients to appropriate care. OBJECTIVE: The aim of our study was to
      pilot a new computer-based method in 43 MS patients to efficiently screen for a
      variety of psychological and physical symptoms of distress. METHODS: Data on
      feasibility and psychological and physical distress (anxiety, depression,
      fatigue, physical disability, cognitive functioning) were collected via a touch
      screen computer. Referral to psychosocial care and rehabilitation was
      retrospectively checked. RESULTS: The results demonstrated that most patients
      (35/40, 88%) considered the screening meaningful and the system easily usable
      (37/40, 93%). Average completion time of the screening was below 8 minutes. Many
      patients (35/40, 88%) had elevated distress levels, of whom the majority was
      referred. CONCLUSIONS: These findings imply that computer-based screening for MS
      related distress incorporated in clinical care is feasible and aids to identify
      psychological or physical needs. A randomized controlled trial with follow-up
      should address whether this screening method could be more effective than routine
      care, and whether it can improve costs and efficiency of care.

PMID- 24902041
TI  - Socio-economic inequalities in the prevalence of multi-morbidity among the rural
      elderly in Bargarh District of Odisha (India).
AB  - BACKGROUND: Multi-morbidity among elderly is increasingly recognized as a major
      public health challenge in most of the developing countries. However, information
      on the size of population suffering from multi-morbidity and socio-economic
      differentials of multi-morbidity is scarce. The objectives of this paper are
      twofold; first, to assess the prevalence of various chronic conditions and
      morbidity among rural elderly and second, to examine the socio-economic and
      demographic factors that have a significant effect on the morbidity. METHODS: A
      cross-sectional survey has been done using multi-stage random sampling procedure
      that was conducted among elderly (60+ years) in Bargarh District of Odisha during
      October 2011-February 2012. The survey was conducted among 310 respondents
      including 153 males and 157 females. Descriptive analyses were performed to
      assess the pattern of multi-morbidity. Logistic regression analyses were used to
      see the adjusted effect of various socio-economic and demographic covariates of
      multi-morbidity. RESULTS: The overall prevalence of multi-morbidity is 57% among
      rural elderly in Bargarh District of Odisha. The most common diseases in rural
      areas are: Arthritis, Chronic Obstructive Pulmonary Disease (COPD), High Blood
      Pressure and Cataract. Results from the logistic regression analyses show that
      age, state of economic independence and life style indicators are the most
      important measured predictors of multi-morbidity. Unlike earlier studies, wealth
      index and education have a marginal impact on multi-morbidity rate. Moreover, the
      occurrence of multi-morbidity is higher for elderly males compared to their
      female counterparts, though the difference is not significant. CONCLUSION: The
      high prevalence of morbidity observed in the present study suggests that there is
      an urgent need to develop geriatric health care services in a developing country
      like India. Any effort to reorganize primary care for elderly people should also
      consider the high prevalence of multi-morbidity among rural elderly in India.

PMID- 24902044
TI  - Intestinal microbiota during early life - impact on health and disease.
AB  - In the first years after birth, the intestinal microbiota develops rapidly both
      in diversity and complexity while being relatively stable in healthy adults.
      Different life-style-related factors as well as medical practices have an
      influence on the early-life intestinal colonisation. We address the impact of
      some of these factors on the consecutive microbiota development and later health.
      An overview is presented of the microbial colonisation steps and the role of the
      host in that process. Moreover, new early biomarkers are discussed with examples
      that include the association of microbiota and atopic diseases, the correlation
      of colic and early development and the impact of the use of antibiotics in early
      life. Our understanding of the development and function of the intestinal
      microbiota is constantly improving but the long-term influence of early-life
      microbiota on later life health deserves careful clinical studies. 

PMID- 24902043
TI  - Novel human butyrylcholinesterase variants: toward organophosphonate
      detoxication.
AB  - Human butyrylcholinesterase (hBChE) is currently being developed as a
      detoxication enzyme for stoichiometric binding and/or catalytic hydrolysis of
      organophosphates. Herein, we describe the use of a molecular evolution method to
      develop novel hBChE variants with increased resistance to stereochemically
      defined nerve agent model compounds of soman, sarin, and cyclosarin. Novel hBChE
      variants (Y332S, D340H, and Y332S/D340H) were identified with an increased
      resistance to nerve agent model compounds that retained robust intrinsic
      catalytic efficiency. Molecular dynamics simulations of these variants revealed
      insights into the mechanism by which these structural changes conferred nerve
      agent model compound resistance. 

PMID- 24902045
TI  - Quantitative correlation of aflatoxin biomarker with dietary intake of aflatoxin
      in Tanzanian children.
AB  - The association between aflatoxin intake from maize-based weaning food and
      aflatoxin albumin adducts (AF-alb) was investigated in 148 Tanzanian children
      aged between 12 and 22 months, at 2 visits 6 months apart. At the first visit
      (storage season) there was a significant correlation at the individual level
      between AF-alb (geometric mean 43.2 pg/mg albumin) and aflatoxin intake
      (geometric mean 81.7 ng/kg b.w./d) through maize-based weaning food (r = 0.51, p
      < 0.01). Overall, this correlation was r = 0.43 (p < 0.01). The AF-alb level in
      weaning-age children in Tanzania closely reflects aflatoxin intake from maize in
      weaning food. Exposure levels suggest children may be at risk from aflatoxin
      associated health effects.

PMID- 24902046
TI  - Complications of allogeneic hematopoietic stem cell transplantation.
AB  - Infection, graft-versus-host disease (GVHD), and to a lesser extent sinusoidal
      obstructive syndrome (SOS) represent the major causes of morbidity and mortality
      in patients undergoing allogeneic hematopoietic stem cell transplantation
      (AHSCT). During the last decade, progress in prevention and treatment of these
      complications led to improvement in the outcome of these patients. Despite the
      fact that nonmyeloablative regimens have been increasingly used in elderly
      patients and in patients with co-morbidities, the nonrelapse related mortality
      remains a challenge and long-term follow-up is required. The objective of this
      manuscript is to provide an updated concise review of the complications of AHSCT
      and of the available treatment interventions.

PMID- 24902047
TI  - Impact of breastfeeding self-efficacy and sociocultural factors on early
      breastfeeding in an urban, predominantly Dominican community.
AB  - BACKGROUND: Latinas have high breastfeeding initiation rates that decrease
      significantly in the first postpartum months. Little is known about the effects
      of self-efficacy and sociocultural factors on early breastfeeding among low
      income Latinas. This study quantifies early breastfeeding rates and identifies
      factors associated with breastfeeding at 4-6 weeks postpartum in our community.
      SUBJECTS AND METHODS: Mothers were recruited from a newborn clinic (NBC) in the
      first postpartum week. Questionnaires in the NBC and 4-6 weeks later assessed
      feeding practices, breastfeeding self-efficacy, and sociocultural factors.
      Feeding practices in the well baby nursery (WBN) were obtained by chart review. A
      scale from "1" (exclusive formula feeding) to "5" (exclusive breastfeeding)
      characterized feeding practices. Paired-sample t tests assessed change in feeding
      practices, and regression analysis assessed the impact of factors on
      breastfeeding at 4-6 weeks. RESULTS: We interviewed 209 women: 86.1% Latina,
      47.3% foreign-born, and 94.2% Medicaid-recipients. Breastfeeding increased from
      WBN to NBC (2.6+/-1.2 to 2.9+/-1.4; p<0.05) and then decreased by 4-6 weeks
      (2.9+/-1.4 to 2.5+/-1.44; p<0.05), without significant change between WBN and 4-6
      weeks. Higher levels of education [beta=0.21 (0.08, 0.56)], breastfeeding a
      previous child for >=6 months [beta=0.35 (0.57, 1.8)], foreign birth [beta=0.2
      (0.06, 1.07)], and higher breastfeeding self-efficacy scores [beta=0.38 (0.02,
      0.05)] were associated with more breastfeeding. Higher breastfeeding self
      efficacy scores were associated with exclusive breastfeeding [adjusted odds
      ratio=1.18 (1.05, 1.32)]. CONCLUSIONS: Breastfeeding self-efficacy was the sole,
      modifiable factor associated with exclusive breastfeeding. Efforts to improve
      breastfeeding self-efficacy may serve to support breastfeeding in this
      population.

PMID- 24902049
TI  - Movements of blue rockfish (Sebastes mystinus) off central California with
      comparisons to similar species.
AB  - Olive (Sebastes serranoides), black (Sebastes melanops), and blue rockfish
      (Sebastes mystinus) are all common inhabitants of nearshore ecosystems on the
      West coast of North America and important components of the recreational fishery
      off California. Acoustic monitoring studies indicate that olive rockfish are
      highly residential and that black rockfish are capable of long migrations and
      have less site fidelity; yet little is known about the long-term movements of
      blue rockfish. External tag-recapture studies indicate that blue rockfish may
      have intermediate movements relative to these congener nearshore species. To
      better understand the site fidelity, and daily and seasonal movements of blue
      rockfish over long (>1-year) time scales, we placed acoustic transmitters into 21
      adult blue rockfish (30-41 cm total length) in Carmel Bay, California. Blue
      rockfish displayed intermediate movement patterns and residency relative to other
      similar kelp forest rockfish species. Two-thirds of tagged blue rockfish (13
      fish) exhibited high residency to the study area (>12 mo). When in residence,
      mean home range of blue rockfish was 0.23 km2, however as many as 30% of tagged
      blue rockfish shifted their core home range area during the study. Most shifts in
      home range occurred during upwelling season, and tagged fish moved up to 3.1 km
      when in residence. Blue rockfish with short residence times were last detected in
      the study area in late winter and early spring. Blue rockfish were observed at
      shallower depths during day than night, likely indicative of diurnal feeding.
      However, over longer time scales, blue rockfish were detected at deeper depths
      during upwelling periods and with increased wave heights. Daily and seasonal
      vertical movements of blue rockfish may be influenced by upwelling conditions and
      local prey abundance. 

PMID- 24902050
TI  - Chiral functionalization of graphene oxide by optically active helical
      substituted polyacetylene chains and its application in enantioselective
      crystallization.
AB  - This article reports an original, versatile strategy to chirally functionalize
      graphene oxide (GO) with optically active helical-substituted polyacetylene. GO
      was first converted into alkynyl-GO containing polymerizable -C=C moieties, which
      took part in the polymerization of another chiral acetylenic monomer, yielding
      the expected GO hybrid covalently grafted with chiral helical polyacetylene
      chains. Transmission electron microscopy, atomic force microscopy, X-ray
      diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray
      photoelectron spectroscopy, and thermogravimetric analyses verified the
      successful attachment of substituted polyacetylene chains on GO by covalent
      chemical bonding. Moreover, circular dichroism effects and UV-vis absorption
      demonstrated that the GO hybrid possessed fascinating optical activity. It also
      largely improved the dispersibility of GO in tetrahydrofuran. The GO-derived
      hybrid was further used as a chiral inducer toward enantioselective
      crystallization of alanine enantiomers. l-Alanine was preferably induced to
      crystallize, forming rodlike crystals. 

PMID- 24902048
TI  - A high through-put screen for small molecules modulating MCM2 phosphorylation
      identifies Ryuvidine as an inducer of the DNA damage response.
AB  - DNA replication is an essential process for cell division and as such it is a
      process that is directly targeted by several anticancer drugs. CDC7 plays an
      essential role in the activation of replication origins and has recently been
      proposed as a novel target for drug discovery. The MCM DNA helicase complex (MCM2
      7) is a key target of the CDC7 kinase, and MCM phosphorylation status at specific
      sites is a reliable biomarker of CDC7 cellular activity. In this work we describe
      a cell-based assay that utilizes the "In Cell Western Technique" (ICW) to
      identify compounds that affect cellular CDC7 activity. By screening a library of
      approved drugs and kinase inhibitors we found several compounds that can affect
      CDC7-dependent phosphorylation of MCM2 in HeLa cells. Among these, Mitoxantrone,
      a topoisomerase inhibitor, and Ryuvidine, previously described as a CDK4
      inhibitor, cause a reduction in phosphorylated MCM2 levels and a sudden blockade
      of DNA synthesis that is accompanied by an ATM-dependent checkpoint response.
      This study sheds light on the previously observed cytotoxity of Ryuvidine,
      strongly suggesting that it is related to its effect of causing DNA damage. 

PMID- 24902051
TI  - Imaging "brain strain" in youth athletes with mild traumatic brain injury during
      dual-task performance.
AB  - Mild traumatic brain injury (mTBI) is a common cause of injury in youth athletes.
      Much of what is known about the sequelae of mTBI is yielded from the adult
      literature, and it appears that it is mainly those with persistent post-injury
      symptoms who have ongoing cognitive and neural abnormalities. However, most
      studies have employed single-task paradigms, which may not be challenging enough
      to uncover subtle deficits. We sought to examine the neural correlates of dual
      task performance in male athletes aged 9-15 years using a functional neuroimaging
      protocol. Participants included 13 youths with a history of mTBI three to six
      months prior to testing and 14 typically-developing controls. All participants
      completed a working memory task in isolation (single-task) and while completing a
      concurrent motor task (dual-task); neural activity during performance was then
      compared between groups. Although working memory performance was similar during
      the single-task condition, increased working memory load resulted in an altered
      pattern of neural activation in key working memory areas (i.e., dorsolateral
      prefrontal and parietal cortices) in youth with mTBI relative to controls. During
      the dual-task condition, accuracy was similar between groups but injured youth
      performed slower than typically-developing controls, suggesting a speed-accuracy
      tradeoff in the mTBI group only. The injured youths also exhibited abnormal
      recruitment of brain structures involved in both working memory and dual-tasking.
      These data show that the dual-task paradigm can uncover functional impairments in
      youth with mTBI who are not highly symptomatic and who do not exhibit
      neuropsychological dysfunction. Moreover, neural recruitment abnormalities were
      noted in both task conditions, which we argue suggests mTBI-related disruptions
      in achieving efficient cognitive control and allocation of processing resources.

PMID- 24902052
TI  - Atomistic account of structural and dynamical changes induced by small binders in
      the double helix of a short DNA.
AB  - Nucleic acids are flexible molecules and their dynamical properties play a key
      role in molecular recognition events. Small binders interacting with DNA
      fragments induce both structural and dynamical changes in the double helix. We
      study the dynamics of a DNA dodecamer and of its complexes with Hoechst 33258,
      which is a minor groove binder, and with the ethidium cation, which is an
      intercalator, by molecular dynamics simulation. The thermodynamics of DNA-drug
      interaction is evaluated in connection with the structure and the dynamics of the
      resulting complexes. We identify and characterize the relevant changes in the
      configurational distribution of the DNA helix and relate them to the
      corresponding entropic contributions to the binding free energy. The binder
      Hoechst locks the breathing motion of the minor groove inducing a reduction of
      the configurational entropy of the helix, which amounts to 20 kcal mol(-1). In
      contrast, intercalations with the ethidium cation enhance the flexibility of the
      double helix. We show that the balance between the energy required to deform the
      helix for the intercalation and the gain in configurational entropy is the origin
      of cooperativity in the binding of a second ethidium and of anti-cooperativity in
      the binding of a third one. The results of our study provide an understanding of
      the relation between structure, dynamics and energetics in the interaction
      between DNA fragments and small binders, highlighting the role of dynamical
      changes and consequent variation of the configurational entropy of the DNA double
      helix for both types of binders. 

PMID- 24902053
TI  - An ongoing battle.

PMID- 24902054
TI  - The role of the community clinician in early detection, referral and treatment of
      critical limb ischaemia.
AB  - Critical limb ischaemia (CLI) is a significant public health issue worldwide,
      with an ever-growing incidence among people over 65. Awareness of CLI is low,
      particularly among non-vascular clinicians, leading to underdiagnosis and
      undertreatment. A diagnosis of CLI is known to have a grave effect on a person's
      quality of life, with devastating outcomes for both their life and limb, often
      resulting in uncontrolled pain, amputation or early death from a cardiovascular
      event. Community nurses and podiatrists are key clinicians who can play a crucial
      and active role in earlier identification, rapid referral and ongoing non
      surgical care for this overlooked population. 

PMID- 24902055
TI  - Training community matrons in basic cognitive behavioural therapy-based
      techniques for patients with COPD.
AB  - People with chronic obstructive pulmonary disease (COPD) experience anxiety and
      depression with a higher prevalence than the general population. Despite this,
      they are under-represented in mental health services on a national scale, but do
      regularly have contact with health-care professionals such as community matrons.
      We aimed to explore the process of CBT-based skills supervision and the practical
      implications for community matrons using CBT-based techniques with COPD clients
      as part of their standard practice. Twenty community matrons took part in a 2-day
      CBT-based skills training programme. Measurements of their knowledge and
      understanding of CBT-based skills were taken before and following the training.
      Additionally, they completed written feedback relating to the training. They were
      then supervised by CBT therapists for 6 months. Written feedback was obtained
      following this and some supervisors participated in a 1-hour focus group to
      discuss the process. Community matrons' knowledge and understanding of CBT-based
      techniques significantly improved following training, although findings did
      indicate that merely training did not always seamlessly translate into effective
      practice. Supervisor feedback suggested that it would be beneficial for community
      matrons to share positive practice of their use of basic CBT-based techniques
      among peers to maximise the perceived value of this approach. 

PMID- 24902056
TI  - The effect of education on community nursing practice in improving the patient
      carer experience at the end of life.
AB  - Successfully completing the 'Foundations in End of Life/Palliative Care' distance
      learning module has had a measurable effect on the knowledge, competence and
      confidence of community nurses in the principles and practice of palliative and
      end-of-life care. An appropriate practice-based education module can empower
      community nursing practice and have a direct impact on improving the patient
      carer experience at the end of life. This article provides evidence from the
      quantitative and qualitative data from pre- and post-module self-assessment
      questionnaires along with the successful completion of an electronic multiple
      choice questionnaire and short-answer classroom test to demonstrate this. 

PMID- 24902057
TI  - Implementing interprofessional learning in the community setting.
AB  - Given the need to facilitate and manage care, making every consultation count,
      knowledge of-and working with-different professional care providers is essential.
      To optimise care outcomes for clients, the adoption of interprofessional working
      is essential. This article describes how interprofessional learning was embedded
      in a community nursing practice placement environment with student nurses and
      students from other professions. 

PMID- 24902058
TI  - European Respiratory Nurses Association.

PMID- 24902059
TI  - Tackling dementia: a new approach.

PMID- 24902060
TI  - Government implementation of domestic violence protection measures nationwide.
AB  - As part of its policy to end violence against women and girls, the UK Government
      is rolling out domestic violence protection powers that will enable police to act
      more quickly in urgent situations. The new provisions follow on from the
      successful roll out of 'Clare's law', which allows information relating to a
      person's previous abusive behaviour to be passed to their partner. This article
      sets out the powers available to the police and court to protect people from
      domestic violence. 

PMID- 24902061
TI  - Dying well in the community: an equation.

PMID- 24902062
TI  - Our food and drink obsession.

PMID- 24902063
TI  - Increased levels of osteopontin in sputum supernatant in patients with COPD.
AB  - BACKGROUND: Osteopontin (OPN) is a phosphorylated acidic glycoprotein that can
      function as both an extracellular matrix molecule and a cytokine. Published data
      support that OPN is upregulated in surgical lung tissue samples of patients with
      COPD. The aim of this study was to determine the levels of OPN in sputum
      supernatants of patients with COPD and to investigate possible associations with
      mediators and cells involved in the inflammatory and remodeling process as well
      as with the extent of emphysema. METHODS: Seventy-seven patients with COPD and 40
      healthy subjects (20 smokers) were studied. All subjects underwent lung function
      tests, sputum induction for cell count identification, and OPN, transforming
      growth factor-beta1, matrix metalloproteinase (MMP)-2, IL-8, and leukotriene-4
      measurement in sputum supernatants. High-resolution CT (HRCT) scan of the chest
      was performed for quantification of emphysema. RESULTS: OPN levels (pg/mL) were
      significantly higher in patients with COPD compared with healthy smokers and
      nonsmokers (median [interquartile range], 1,340 [601, 6,227] vs 101 [77, 110] vs
      68 [50, 89], respectively; P < .001). Regression analysis showed a significant
      association between OPN and sputum neutrophils, IL-8, MMP-2, and the extent of
      emphysema. The associations previously listed were not observed in healthy
      subjects. CONCLUSIONS: OPN levels are higher in patients with COPD compared with
      healthy subjects. OPN may play a role in the neutrophilic inflammation and in the
      pathogenesis of emphysema.

PMID- 24902064
TI  - Acantholactam and pre-neo-kauluamine, manzamine-related alkaloids from the
      Indonesian marine sponge Acanthostrongylophora ingens.
AB  - Two new manzamine alkaloids, acantholactam (3) and pre-neo-kauluamine (4), were
      isolated from the marine sponge Acanthostrongylophora ingens along with manzamine
      A (1) and neo-kauluamine (2). Acantholactam contains a gamma-lactam ring N
      substituted with a (Z)-2-hexenoic acid moiety and is proposed to be
      biosynthetically derived from manzamine A by oxidative cleavage of the eight
      membered ring. Compound 4 was converted to the dimer 2 during storage, suggesting
      nonenzymatic dimer formation. Among the four isolated compounds, 1, 2, and 4
      showed proteasome inhibitory activity. 

PMID- 24902065
TI  - A 500 year sediment lake record of anthropogenic and natural inputs to Windermere
      (English Lake District) using double-spike lead isotopes, radiochronology, and
      sediment microanalysis.
AB  - A high-resolution record of pollution is preserved in recent sediments from
      Windermere, the largest lake in the English Lake District. Data derived from X
      ray core scanning (validated against wavelength dispersive X-ray fluorescence),
      radiochronological techniques ((210)Pb and (137)Cs) and ultrahigh precision,
      double-spike mass spectrometry for lead isotopes are combined to decipher the
      anthropogenic inputs to the lake. The sediment record suggests that while most
      element concentrations have been stable, there has been a significant increase in
      lead, zinc, and copper concentrations since the 1930s. Lead isotope down-core
      variations identify three major contributory sources of anthropogenic
      (industrial) lead, comprising gasoline lead, coal combustion lead (most likely
      source is coal-fired steam ships), and lead derived from Carboniferous Pb-Zn
      mineralization (mining activities). Periods of metal workings do not correlate
      with peaks in heavy metals due to the trapping efficiency of up-system lakes in
      the catchment. Heavy metal increases could be due to flood-induced metal inwash
      after the cessation of mining and the weathering of bedrock in the catchment. The
      combination of sediment analysis techniques used provides new insights into the
      pollutant depositional history of Windermere and could be similarly applied to
      other lake systems to determine the timing and scale of anthropogenic inputs. 

PMID- 24902069
TI  - [Real-time MRI/US fusion-guided biopsy improves detection rates of prostate
      cancer in pre-biopsied patients].
AB  - BACKGROUND: According to the guidelines of the European Association of Urology
      (EAU) on prostate cancer (PCa) in 2013, patients with increasing prostate
      specific antigen (PSA) levels, suspicious digital rectal examination (DRE) or
      high-grade prostatic intraepithelial neoplasia after negative prostate biopsy
      (PB) should undergo a repeat biopsy. Low cancer detection rates in the repeat
      biopsy illuminate the dilemma of the international gold standard of transrectal
      ultrasound (TRUS) guided PB in the detection of PCa. Our study evaluated the
      combination of TRUS and prostate magnetic resonance imaging (MRI) and its
      reported high sensitivities and high specificities by using real-time MRI/US
      fusion-guided biopsy. The detection of clinically significant PCa was
      investigated. MATERIAL AND METHODS: 128 consecutive patients in the period of
      January 2012 to August 2013 were included. All patients had at least one TRUS
      guided biopsy with negative findings and the clinical indication for a systematic
      re-biopsy. Prior to the MRI/US fusion all patients underwent a 3 Tesla prostate
      MRI without endorectal coil. The MRI data were uploaded to a modern US system.
      The B-mode, power-mode, elastography and CEUS imaging were used to classify the
      suspicious lesions from the MRI on a scale of 0-3 and a US sum score was
      calculated. The lesion was consecutively biopsied by real-time MRI/US fusion
      followed by a systematic 10 core biopsy. RESULTS: Among 128 patients 51 PCa could
      be detected (39.8%). From these 51 PCa cases, clinically significant PCa was
      detected by MRI/US fusion-guided biopsy as follows: Gleason score >7 in 9 of 10
      patients; Gleason score=7 in 14 of 20 patients and Gleason score <7 in 13 of 21
      patients. A positive correlation was shown between the US sum score and the
      associated PI-RADS score in 65 patients in whom lesions were classified by PI
      RADS. A positive correlation was further shown between the US sum score and the
      Gleason score of all suspicious and biopsied lesions. MRI/US fusion and TRUS
      guided biopsy combined, detected 30 of 51 PCa; 6 of 51 PCa were detected by
      MRI/US fusion alone and 15 of 51 PCa by conventional TRUS-guided biopsy alone.
      CONCLUSION: Real-time MR/US fusion increases detection rates of PCa in patients
      undergoing repeat biopsy. Especially, clinically significant PCa with a Gleason
      score >= 7 were almost exclusively detected by MR/US fusion-guided biopsy.

PMID- 24902070
TI  - [Ureteroarterial fistula - pathogenesis, diagnostics, and therapeutic outcome].
AB  - Although ureteroarterial fistulas are rare, they result in a high mortality
      because of the massive urogenital haemorrhage. The diagnosis is often difficult
      even when invasive measures are applied. Including the ureteroarterial fistula in
      the diagnostic process in cases of macrohaematuria with a positive medical
      history can be helpful. A ureteroarterial fistula typically develops in pa-tients
      who have undergone pelvic surgery and radiation as well as after long-term
      ureteral stents. Patients are usually multimorbid. The treatment of choice
      consists of fistula exclusion by stent graft deployment in the iliac artery and
      application of a ureteral stent or a ureterostomy. The significance of surgical
      treatment is diminishing. The long-term results of endovascular treatment,
      however, are inconsistent because of stent infections and recurrent bleeding.
      Therefore, close patient surveillance and cooperation among the treating
      specialists is necessary.. 

PMID- 24902071
TI  - [Implementation of a scale on stone baskets].
AB  - BACKGROUND: Complications after endoscopic retrieval of kidney and ureter stones
      are obviously related to the size of the stones as well as the experience of the
      surgeon and other factors. During the procedure it is sometimes difficult for
      surgeons to estimate stone size and therefore give prognostic advises. The visual
      perception of the stone size depends on the shape, colour, distance to the
      renoscope and dilatation of the ureter. This is the so-called binding problem,
      because shape, color and direction of motion are processed separately by
      different population of optical neurons. In order to establish a better
      prognostic ratio, especially for less experienced surgeons we established an
      intraoperative semi-quantitative measurement of the stone size supported by a
      stone basket. MATERIALS AND METHODS: We modified the tipped nitinol stone baskets
      from the company Urotech with diameters of 2.5, 3.0 and 4 Ch. The handle of this
      basket has a spring mechanism, which automatically closes the basket and provides
      a predefined fixation force of the stones within the basket. On the handle we
      established a non-linear scale in mm by grabbing standardized balls or
      standardized screws. RESULTS: The scales are nonlinear because of the nonlinear
      relation between the diameter of the stone and the distance of the slider. Also
      the scales differ in between the basket size, because of the different strain
      conditions due to the different wire sizes and materials or the spring and
      basket. CONCLUSIONS: This scale could be an important orientation for a surgeon
      during endourological procedures to estimate stone sizes. It could be used also
      for the documentation of the size of fragments after an endourologic lithotripsy
      and could help in the decision for or against an extraction. Finally it could be
      very interesting for other disciplines like gastroenterology. The scale should be
      validated in further clinical trials.

PMID- 24902068
TI  - Back to the future with phenotypic screening.
AB  - There are no disease-modifying drugs for any old age associated neurodegenerative
      disease or stroke. This is at least in part due to the failure of drug developers
      to recognize that the vast majority of neurodegenerative diseases arise from a
      confluence of multiple toxic insults that accumulate during normal aging and
      interact with genetic and environmental risk factors. Thus, it is unlikely that
      the current single target approach based upon rare dominant mutations or even a
      few preselected targets is going to yield useful drugs for these conditions.
      Therefore, the identification of drug candidates for neurodegeneration should be
      based upon their efficacy in phenotypic screening assays that reflect the biology
      of the aging brain, not a single, preselected target. It is argued here that this
      approach to drug discovery is the most likely to produce safe and effective drugs
      for neurodegenerative diseases. 

PMID- 24902072
TI  - [Enuresis].
AB  - Enuresis in childhood and adolescence is a common symptom that significantly
      affects the quality of life of the patients and their social environment.
      Advanced diagnostic and therapeutic measures have significantly improved the
      treatment of affected children in the last 10 years in Germany. With the help of
      an often sufficient non-invasive diagnostic assessment it is possible to assign
      the symptom to a diagnostic category. This category forms the basis for a
      successful therapy. A high level of motivation and willingness to cooperate of
      the children and their families are therapeutic premises. In present-day
      treatment of functional urinary incontinence urotherapy has the highest priority.

PMID- 24902074
TI  - [Internal urethrotomy].

PMID- 24902073
TI  - [Internal urethrotomy].

PMID- 24902076
TI  - A culture of health and healthiest nation initiatives: the relevance of health
      care management research.

PMID- 24902075
TI  - Diathermy versus scalpel in Limberg flap in pilonidal sinus surgery. A
      prospective randomized trial.
AB  - BACKGROUND: Rhomboid excision with Limberg flap repair (RELIF) is an effective
      surgical procedure in pilonidal sinus disease (PSD) treatment. This study aimed
      to compare outcome of diathermy and scalpel in RELIF procedure in PSD surgery.
      METHODS: Patients undergoing RELIF procedure due to PSD at Adana Numune Training
      and Research Hospital between January 2012 and September 2012 were randomly
      assigned to diathermy (n=30) or scalpel (n=30) groups. The primary outcomes
      measured were duration of operation, drainage volume, postoperative numerical
      pain intensity scale (NPIS) scores, complications, duration of hospitalization
      length and time to return to daily activity. RESULTS: The mean age was 26.2 years
      (17-44 years). The mean operation duration was significantly lower in diathermy
      group (p=0.0001). Postoperative total NPIS score within the first 24 h was
      significantly lower in diathermy group (p=0.001). However, there were not any
      significant differences in term of NPIS scores in day 3 and day 7. There were no
      significant differences in terms of total drain output, drain removal time and
      length of hospital stay. There were no significant differences between groups in
      terms of duration to sit comfortably, return to daily activity and work.
      Recurrence of PSD was emerged in one patient in the diathermy group. CONCLUSION:
      Diathermy dissection in RELIF procedure in pilonidal sinus surgery is a safe
      technique and decreased operation time and postoperative pain.

PMID- 24902079
TI  - Oxaphosphirane-borane complexes: ring strain and migratory insertion/ring-opening
      reactions.
AB  - DFT-based HSAB-related parameters predict most favorable P- versus O-complexation
      of parent oxaphosphirane (1) with a variety of borane reagents BR3 (2). In
      general, strong P-B bonds are formed, especially for R: H (3a), Cl (3d), and C6F5
      (3g), in agreement with large dissociation energies, whereas O-B bonds are
      usually weaker. A remarkable increase in ring strain is observed upon P
      complexation of phosphirane or oxaphosphiranes, especially in the case of 3g and
      3d, whereas a moderate decrease occurs in the case of O-complexation for both
      oxirane and oxaphosphiranes. Stronger P-B bonds also correlate with larger charge
      transfer from the oxaphosphirane to the borane units. This in turn increases
      electron density at the boron center and weakens all B-R bonds, thus enabling
      migratory insertion/ring-opening reactions in which a substituent from the borate
      center shifts to a ring atom; these reactions are additionally driven by release
      of the high ring strain of P-complexes 3. 

PMID- 24902078
TI  - Overall view of chemical and biochemical weapons.
AB  - This article describes a brief history of chemical warfare, which culminated in
      the signing of the Chemical Weapons Convention. It describes the current level of
      chemical weapons and the risk of using them. Furthermore, some traditional
      technology for the development of chemical weapons, such as increasing toxicity,
      methods of overcoming chemical protection, research on natural toxins or the
      introduction of binary technology, has been described. In accordance with many
      parameters, chemical weapons based on traditional technologies have achieved the
      limit of their development. There is, however, a big potential of their further
      development based on the most recent knowledge of modern scientific and technical
      disciplines, particularly at the boundary of chemistry and biology. The risk is
      even higher due to the fact that already, today, there is a general acceptance of
      the development of non-lethal chemical weapons at a technologically higher level.
      In the future, the chemical arsenal will be based on the accumulation of
      important information from the fields of chemical, biological and toxin weapons.
      Data banks obtained in this way will be hardly accessible and the risk of their
      materialization will persist. 

PMID- 24902077
TI  - Differential effects of indoxyl sulfate and inorganic phosphate in a murine
      cerebral endothelial cell line (bEnd.3).
AB  - Endothelial dysfunction plays a key role in stroke in chronic kidney disease
      patients. To explore the underlying mechanisms, we evaluated the effects of two
      uremic toxins on cerebral endothelium function. bEnd.3 cells were exposed to
      indoxyl sulfate (IS) and inorganic phosphate (Pi). Nitric oxide (NO), reactive
      oxygen species (ROS) and O2*- were measured using specific fluorophores.
      Peroxynitrite and eNOS uncoupling were evaluated using ebselen, a peroxide
      scavenger, and tetrahydrobiopterin (BH4), respectively. Cell viability decreased
      after IS or Pi treatment (p < 0.01). Both toxins reduced NO production (IS, p <
      0.05; Pi, p < 0.001) and induced ROS production (p < 0.001). IS and 2 mM Pi
      reduced O2*- production (p < 0.001). Antioxidant pretreatment reduced ROS levels
      in both IS- and Pi-treated cells, but a more marked reduction of O2*- production
      was observed in Pi-treated cells (p < 0.001). Ebselen reduced the ROS production
      induced by the two toxins (p < 0.001); suggesting a role of peroxynitrite in this
      process. BH4 addition significantly reduced O2*- and increased NO production in
      Pi-treated cells (p < 0.001), suggesting eNOS uncoupling, but had no effect in IS
      treated cells. This study shows, for the first time, that IS and Pi induce
      cerebral endothelial dysfunction by decreasing NO levels due to enhanced
      oxidative stress. However, Pi appears to be more deleterious, as it also induces
      eNOS uncoupling.

PMID- 24902081
TI  - Adsorption of water on graphene/Ru(0001)-an experimental ultra-high vacuum study.
AB  - Data for water adsorption on epitaxial graphene grown on Ru(0001) at ultra-high
      vacuum (clean conditions) are discussed. Accordingly, water adsorption was not
      affected by the support. The interaction is not strictly hydrophobic. We propose
      simple rules based on ultra-high vacuum kinetics to classify the water-graphene
      support interactions. 

PMID- 24902080
TI  - Recurrence of retroperitoneal Merkel cell carcinoma. A case report.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a neuroendocrine malignant neoplasm
      that usually has its primary location on the skin. It often metastasizes to lymph
      nodes, liver, lungs, bones and brain. Actually there have been few cases of MCC
      of the retroperitoneal region without a primary skin lesion. CASE PRESENTATION:
      Our case is a male of 55 year old who initially underwent a partial resection
      (R1) of a bulky pelvic mass; the histopathological analysis and the
      immunoistochemistry showed the presence of neuroendocrine Merkel cells. The
      patient underwent 6 cycles of postoperative chemotherapy (carbon platinum and
      etoposide) and adjuvant radiotherapy. Afterwards the patient underwent surgery
      again with the complete resection of the tumour. DISCUSSION: The histopatological
      and immunoistochemistry analysis of the first and the second surgical samples
      confirmed the diagnosis of a retroperitoneal high-grade neuroendocrine carcinoma
      with a high mitosis index. The immunoistochemistry profile showed neoplastic cell
      with: CD 20+, synaptophysin +, TTF-1-, neurofilaments +, CK 7-, chromogranin,
      Ki67 90%. In the patient's medical history no skin localizations were mentioned.
      CONCLUSION: The hypothesis of a MCC with a primary retroperitoneal localization
      has been strength by the histopathological and immunoistochemistry analysis of
      two intra-operative samples from two different surgical procedure and from the
      absence of either a primary skin location or of secondary recurrences. Is
      therefore reinforced the theory that from a cell into a retroperitoneal lymph
      node can arise a retroperitoneal mass originating a Merkel cell tumour.

PMID- 24902082
TI  - Dose-volume analysis of radiation-induced optic neuropathy after single-fraction
      stereotactic radiosurgery.
AB  - BACKGROUND: The risk of radiation-induced optic neuropathy (RION) is the primary
      limitation of single-fraction stereotactic radiosurgery (SRS) for many patients
      with parasellar lesions. OBJECTIVE: To define the normal tissue complication
      probability of the anterior visual pathways (AVPs) after single-fraction SRS.
      METHODS: Retrospective review comparing visual function before and after SRS in
      133 patients (266 sides) with pituitary adenomas having SRS between October 2007
      and July 2012. Patients with prior radiation therapy or SRS were excluded. The
      median follow-up after SRS was 32 months. RESULTS: The median maximum point dose
      to the AVP was 9.2 Gy (interquartile range [IQR], 6.9-10.8). One hundred seventy
      four sides (65%) received >8 Gy: the median 8-Gy volume was 15.8 mm3 (IQR, 3.7
      36.2). Ninety-four sides (35%) received >10 Gy; the median 10-Gy volume was 1.6
      mm3 (IQR, 0.5-5.3). Twenty-nine sides (11%) received >12 Gy; the median 12-Gy
      volume was 0.1 mm3 (IQR, 0.1-0.6). No patient had a RION after SRS. The chances
      of developing a RION at the 8-Gy, 10-Gy, and 12-Gy volumes (95% confidence
      interval) in this series were 0% to 2.6%, 0% to 4.7%, and 0% to 13.9%,
      respectively. CONCLUSION: The AVP in patients without prior radiation treatments
      can safely receive radiation doses up to 12 Gy with a low risk of RION. Although
      additional studies are needed to better delineate the normal tissue complication
      probability of the AVP, adherence to the AVP radiation tolerance guidelines
      developed 20 years ago (8 Gy) limits the applicability and potentially the
      effectiveness of single-fraction SRS for patients with lesions in the parasellar
      region.

PMID- 24902083
TI  - Effect of cinnamon (Cinnamomum zeylanicum) essential oil supplementation on lamb
      growth performance and meat quality characteristics.
AB  - A trial was conducted to examine the effect of cinnamon essential oil
      supplementation on lamb growth performance and meat quality. Sixteen male lambs
      were randomly assigned to two groups. The first group served as control and was
      given a basal diet, and the second group was given the same diet supplemented
      with cinnamon oil (1 ml/kg of concentrated feed) for 35 days. Incorporation of
      cinnamon oil did not affect growth performance (P>0.05). Meat pH, colour, water
      holding capacity, shear force, intramuscular fat and lipid oxidation values of
      longissimus thoracis muscle were not significantly influenced by cinnamon oil
      supplementation (P>0.05). The post-inoculation counts of Salmonella enteritidis
      and Listeria monocytogenes on raw meat during refrigerated storage for 6 days did
      not differ (P>0.05) between the two groups. The results show that cinnamon oil
      supplementation may not have the potential to improve lamb growth performance and
      meat quality characteristics. 

PMID- 24902085
TI  - Tailored silica-antibiotic nanoparticles: overcoming bacterial resistance with
      low cytotoxicity.
AB  - New and more aggressive antibiotic resistant bacteria arise at an alarming rate
      and represent an ever-growing challenge to global health care systems.
      Consequently, the development of new antimicrobial agents is required to overcome
      the inefficiency of conventional antibiotics and bypass treatment limitations
      related to these pathologies. In this study, we present a synthesis protocol,
      which was able to entrap tetracycline antibiotic into silica nanospheres.
      Bactericidal efficacy of these structures was tested against bacteria that were
      susceptible and resistant to antibiotics. For nonresistant bacteria, our
      composite had bactericidal efficiency comparable to that of free-tetracycline. On
      the other hand, the synthesized composites were able to avoid bacterial growth of
      resistant bacteria while free-tetracycline has shown no significant bactericidal
      effect. Finally, we have investigated the cytotoxicity of these nanoparticles
      against mammalian cells to check any possible poisoning effect. It was found that
      these nanospheres are not apoptosis-inducers and only a reduction on the cell
      replication rate was seen when compared to the control without nanoparticles. 

PMID- 24902086
TI  - Heart in anatomy history, radiology, anthropology and art.
AB  - BACKGROUND: Anthropologic, artistic and medical significance of heart inspired
      usto undertake this multidisciplinary study. MATERIALS AND METHODS: Amongst the
      24 obtained echocardiograms and phonograms, 1 was used for a Photoshop
      processing. In addition, over 20,000 art work reproductions were examined in this
      study. RESULTS: Artistic and symbolic presentation of heart started some 15,000
      years ago. First heart models were made by the Egyptian and Olmec civilisations.
      Ancient cultures regarded heart as the seat of the soul, spirit and intelligence.
      First anatomical and artistic images of heart were created by Leonardo da Vinci
      in the15th century, and first wax models by the Italian anatomists in the 17th
      century. Mediaeval religious symbolism of heart was replaced in the Renaissance
      and later on mainly by its role in the romantic love. Anatomical heart art
      continued in the 18th and 19th centuries through the works of Senac, Cloquet,
      Hirschfeldand Bourgery. Some modern artists, such as Dali, Kahlo, Rivera, Warhol,
      Ivanjicki, Vital, Kober and Mastrlova, created the anatomical heart images or
      sculptures, whereas some others, such as Duchamp, Klee, Miro, Matisse and Dine,
      presented heart symbol in their artworks. New radiologic technologies produce
      fine images of heart, some of which are similar to the works of modern artists.
      CONCLUSIONS: Heart biology and symbolism have had a tremendous influence on our
      culture, including art and medical sciences. New radiologic techniques and
      computer technology have produced such images of heart, which substantially
      improved diagnosis, but also enhanced the heart aesthetics.

PMID- 24902087
TI  - Cardiovascular dysphagia - anatomical and clinical implications.
AB  - Cardiovascular dysphagia is rare. The aetiologies can be congenital, acquired
      oriatrogenic. The severity of dysphagia can be mild or severe, consistent or
      progressive, depending on the nature of the cardiovascular disorder and the
      impact for oesophageal compressions. The diagnostic work-up includes standard
      chest radiography, chest computed tomography, endoscopy, barium swallow test and
      manometry. Treatment can be conservative, surgical or palliative according to the
      nature of the disorder and the severity of the symptom. Prognoses of the patients
      are always good. Although cardiovascular dysphagia is continuously reported as
      sporadic cases, there have not been any comprehensive declarations of the
      conditions in the literature. Present article aims to make a comprehensive review
      of cardiovascular dysphagia. 

PMID- 24902088
TI  - Macro-anatomical variation of the olfactory apparatus in some Indian teleosts
      with special reference to their ecological habitat.
AB  - The anatomy of the peripheral olfactory apparatus (i.e. olfactory lamellae,
      olfactorychambers, accessory nasal sacs, olfactory nerve tracts, olfactory bulbs
      and brain) of some teleosts, viz. Pseudapocryptes lanceolatus (Bloch and
      Schneider, 1801) - an air breathing mudskipper, Lepidocephalichthys guntea
      (Hamilton, 1822) - a freshwater scavenger fish and Mastacembelus armatus
      (Lacepede, 1800) - a freshwater potamodromous fish, has been studied in relation
      to their specific ecological habitat. Live, adult, sex-independent fish species
      were collected from the local markets of West Bengal, India, and acclimatised
      with the laboratory conditions (for 72 h at 32 degrees C). The specimens were
      anaesthetised by MS-222 (dose: 100-200 mg/L). Olfactory apparatuses were
      dissected out and fixed inaqueous Bouin's solution. The macro- and
      microstructures (using haematoxylin and eosin) of the olfactory apparatuses were
      examined under binocular light microscope (LM) and trinocular LM (Primo Star;
      Carl Zeiss Microscpy, GmbH, Germany) respectively. P. lanceolatus possesses
      unilamellar olfactory apparatus at therounded snout, whereas L. guntea shows
      small rosette with 18 to 24 lamellae oneither side of the elliptical snout.
      Elongated olfactory rosette (number of lamellae ranges from 60 to 76) is present
      at the pointed snout of M. armatus. Morpho-anatomical variation in snout
      structure of the respective species is an indicative of divergence in ecological
      habitat, but variation in olfactory apparatus is significant for species-specific
      differentiation. Pseudostratified olfactory neuroepithelial components (i.e.
      sensory receptor cell, supporting cell and basal cell) show striking similarities
      amongst these species. Therefore comparative anatomical changes of the snout and
      olfactory apparatus are not only representing ecological habitat based on
      interspecific variation, but may also indicate the phylogenetic relation amongst
      said species. 

PMID- 24902089
TI  - Quantification of white matter fibre pathways disruption in frontal transcortical
      approach to the lateral ventricle or the interventricular foramen in diffusion
      tensor tractography.
AB  - Pathologies occupying the interventricular foramen (foramen of Monro - FM) or the
      anterior part of lateral ventricle (LV) are accessed by the transcortical or
      transcallosal route. As severing of rostral corpus callosum has been deemed
      inferior to cortical incision, the approaches through various points of frontal
      lobe have been developed. Superior (F1), middle (F2) frontal gyrus or
      occasionally superior frontal sulcus are used as an entry of neurosurgical
      corridor. In spite of the fact that every approach to LV or FM causes its
      characteristic irreversible damage to white matter, to date all of transcortical
      routes are regarded as equivalent. The current study compared the damage of main
      neural bundles between virtualtrans-F1 and trans-F2 corridors by means of
      diffusion tensor tractography method (DTT) in 11 magnetic resonance imaging (MRI)
      exams from clinical series (22 hemispheres, regardless of dominance). Corpus
      callosum, cingulum, subdivisions I and II of superior longitudinal fasciculus
      (SLF I and SLF II), corticoreticular as well as pyramidal tracts crossing both
      approaches were subjected to surgical violation. Both approaches served a similar
      total number of fibres (0.94 to 1.78 [* 103]).Trans-F1 route caused significantly
      greater damage of total white matter volume(F1: 8.26 vs. F2: 7.16 mL), percentage
      of SLF I fibres (F1: 78.6% vs. F2: 28.6%)and cingulum (F1: 49.4% vs. F2: 10.6%),
      whereas trans-F2 route interrupted morecorticoreticular fibres (F1: 4.5% vs. F2:
      30.7%). Pyramidal tract (F1: 0.6% vs. F2:1.3%) and SLF II (F1: 15.9% vs. F2:
      26.2%) were marginally more vulnerable incase of the access via middle frontal
      gyrus. Both approaches destroyed 7% of callosal fibres. Summarising the above DTT
      findings, trans-F2 route disrupted a greater number of fibres from eloquent
      neural bundles (SLF II, pyramidal and corticoreticular tracts), therefore is
      regarded as inferior to trans-F1 one. Due to lack of up-to-date guidelines with
      recommendations of the approaches to LV or FM, an individual preoperative
      planning based on DTT should precede a surgery. 

PMID- 24902090
TI  - The venous system of the human foetal spinal cord. Scanning electron microscope
      of vascular corrosion casts.
AB  - The investigation was carried out on 16 human foetal cadavers at the age of 17-23
      weeks from the time of conception. The foetal vascular system was injected with
      the synthetic resin MERCOX CL-2R and analysed in scanning electron microscope.The
      vascular system of the foetal spinal cord was studied. The foetal vascular system
      was characterised by high variability concerning the number, course and
      localisation of blood vessels. It contained numerous anastomoses with the
      internal spinal venous plexuses, which included anterior and posterior radicular
      veins. Large arteries running on the surface of the spinal cord are accompanied
      by the homoname veins. The venous system of the investigated foetuses was divided
      into 2 categories of veins: internal veins responsible for the drainage of blood
      from the central area, that is central and peripheral veins coming radially to
      the surface of the spinal cord and external veins, which form the venous system
      of the surface of the spinal cord. The venous system of the foetal spinal cord
      was also examined as to the presence of the valves. 

PMID- 24902091
TI  - Height at the withers estimation in the horses based on the internal dimension of
      cranial cavity.
AB  - The investigations were carried out on 17 modern half-breed horse skulls and
      their metacarpal and metatarsal bones. The basal length (BL), total length (TL),
      internal cranial cavity dimension and maximal length of metacarpus and metatarsus
      and maximal lateral length of metacarpus and metatarsus were measured according
      to Kiesewalter and von den Driesch. During height at the withers estimation, the
      Kiesewaler and Vitt methods were used. The Wyrost and Kucharczyk mathematical
      formula was modified for height at the withers calculation (Hestmd = 1.016 * D)
      in horses. All height at the withers estimation methods were statistically
      analysed and compared. The analysis of variance ANOVA proved the lack of
      significant difference between the investigated values. The results achieved
      using Wyrost and Kucharczyk modified method are strongly comparable to
      Kiesewalter methods results computed using the metacarpal and metatarsal bones
      measurements. The height at the withers calculated on the basis of TL slightly
      differs from 2 above-mentioned methods. The BL Vitt's method was the least exact.

PMID- 24902092
TI  - Anthropometric measurements of the orbita and gender prediction with three
      dimensional computed tomography images.
AB  - BACKGROUND: The aim of the study was to investigate the orbital anthropometric
      variations in the normal population using three-dimensional computed tomography
      (3D-CT) images and to define the effects of age and gender on orbital
      anthropometry. MATERIALS AND METHODS: Three-dimensional orbita CT of 280
      patients, obtained for various reasons, were retrospectively evaluated in 772-bed
      referral and tertiary-care hospital between April 2011 and June 2012. Using 3D
      images, orbital width, height, biorbital-interorbital diameter and orbital index
      were measured. Measurements were obtained comparing right and left sides and male
      to female. The relation of the results with age and gender was analysed. RESULTS:
      Right orbit was found to be wider than left (p < 0.0001). Male patients had wider
      (p < 0.0001) and higher (p = 0.0001) orbits. Right orbital index was found to be
      smaller than the left one (p = 0.005). No differences were found between the
      genders in terms of right and left orbital indexes (p > 0.05). Biorbital (p <
      0.0001) and interorbital (p = 0.01) widths were found to be higher in males.
      There was no relation between the age change and the parameters defined (p >
      0.05). CONCLUSIONS: No relation was found between age and orbital measurements.
      It was concluded that orbital images obtained with 3D-CT may be used as a method
      for gender evaluation.

PMID- 24902093
TI  - Individual variations in the vascular content of retrodiscal tissue in the
      temporomandibular joint: a study using histological sections of human foetuses
      and magnetic resonance images of adults without pathology.
AB  - The vascular content of retrodiscal tissue in the temporomandibular joint (TMJ)
      plays a critical role in joint function, and its morphology is therefore likely
      relatedto TMJ pain. Using histological sections of human foetuses as well as T2
      weighted magnetic resonance images (MRI), we measured the vascular content of
      retrodiscal tissue. MRI showing no pathology in and around the TMJ were obtained
      from18 young patients who had been suffering from headache. In 10 small foetuses
      (12-14 weeks of gestation) as well as 10 larger foetuses (30-37 weeks), the
      vascular content showed individual variations exceeding 5 times the minimum value
      (0.24 vs. 0.04 mm2 per 1 mm2), but no difference between foetal stages was
      evident. In the MRI from young adults, the variation was less than twice the
      minimum value (13.6 vs. 8.7 mm2 per 100 mm2). The vascular density appeared to be
      lower in adults than in foetuses. In both foetuses and adults, the thickness
      (anteroposterior length) of the tissue did not correlate with the vascular
      sectional area. These findings suggest that the considerable inter-individual
      differences evident in the vascular content of foetal retrodiscal tissue may be
      reduced during further development. 

PMID- 24902094
TI  - Evaluation of left renal vein and inferior vena cava variations through routine
      abdominal multi-slice computed tomography.
AB  - BACKGROUND: The aim of this study was to evaluate the frequency of left renal
      vein (LRV) and inferior vena cava (IVC) variations and the effect of gender on
      this frequency, as well as the presence of associated abdominal pathologies.
      MATERIALS AND METHODS: Multi-slice computed tomography (MSCT) images from 746
      patients were evaluated retrospectively. RESULTS: Left renal vein variations were
      identified in 9.8% of cases, while retroaortic LRV (RLRV) and circumaortic LRV
      (CLRV) were found in 7.4% and 2.4% of cases, respectively. No significant
      correlation was found between gender and LRV variations (p = 0.797). Of the cases
      with LRV and IVC variations, 73% had abdominal pathologies, the most common of
      which were nephrolithiasis, which appeared in 18 (32%) cases, and renal cysts,
      which appeared in 14 (25.4%) cases. CONCLUSIONS: MSCT is a rapid and reliable
      method of identifying LRV and IVC variations and associated abdominal
      pathologies.

PMID- 24902095
TI  - 'Venous lakes' - a corrosion cast scanning electron microscopy study of regular
      and myomatous human uterine blood vessels.
AB  - BACKGROUND: The aim of this study was to evaluate the venous structure of
      regularand myomatous human uteri, using corrosion casting and scanning electron
      microscopy (SEM). Special attention was paid to the endometrium and the socalled
      'venous lakes'. MATERIALS AND METHODS: Uteri collected at autopsy (n = 67) were
      injected with Mercox CL-2R resin, which penetrated the capillary bed and filled
      both arteriesand veins. After the polymerisation of the resin, the corrosion was
      performed. The obtained vascular casts, visualising all vessels including
      capillaries, were examinedusing scanning electron microscopy. RESULTS: Amongst
      the 67 uteri prepared for the corrosion casting, only 22 (15 containing
      leiomyomata) yielded casts of acceptable quality for SEM assessment. Veins of the
      endometrium and the myometrium were present in the form of a chaotic network,
      which did not run parallel to the arterialsystem, but was rather independent.
      Microscopic venous dilations ('venouslakes') were observed both within the
      functional layer of the endometrium and the myometrium. They were digit-like in
      shape and could be compared to venous sinuses. They drained the subendothelial
      capillary plexus and were supplied by numerous capillaries and venules. Their
      size ranged from 270 to 420 MUm. Those dilatations were absent in the outer
      myometrium and the perimetrium, as well as the uterine cervix. We have not
      observed any arteriovenous anastomoses. CONCLUSIONS: The myomatous uteri tend to
      have larger venous lakes than the normal uteri. The number and size of venous
      lakes increases with menstrual cycle progression. Further data on morphology and
      changes in venous lakesusing scanning electronic microscopy should be acquired.

PMID- 24902096
TI  - Myocardial bridge and coronary arteries: morphological study and clinical
      significance.
AB  - Myocardial bridge (MB) is the myocardial bundles covering a segment of a coronary
      artery or one of its branches. This work aimed to study the morphological
      properties of MB and their effects on the structure of the dominant coronary
      artery. Sixty adult human hearts (40 male and 20 female) were obtained from the
      Anatomy Department, Faculty of Medicine, King Abdulaziz University. Dissection o
      fthe coronary arteries and their main branches was done. Number, site, length and
      thickness of MB were determined in correlation with coronary dominancy. External
      diameter of proximal and distal segments of bridged branches and histology of the
      different segments of the anterior interventricular artery were examined as well.
      Thirty-six MB were observed in 27 (45%) hearts (18 male and 9 female). MB were
      mostly observed on the middle segment of the anterior interventricular artery
      (52.8%) and to a lesser extent on its diagonal branch (13.8%), posterior
      interventricular artery (13.8%), median and left marginal branches (5.6%), and
      right coronary artery stem (2.8%). In 30% out of 56.7% of right, in 8.3% out of
      26.7% of balanced and in 6.7% out of 16.7% of left dominant hearts revealed MB.
      The mean length of MB was 24.9 +/- 1.98 mm and that of their thickness was 2.28
      +/- 0.13 mm. Morphological differences in external diameter and histological
      structure of the different parts of bridged branch were observed. Knowledge of
      morphological aspects and effects of MB provide better therapeutic and surgical
      interventions for clinicians dealing with patients having MB. 

PMID- 24902097
TI  - Estimation of spleen volume and surface area of the newborns' cadaveric spleen
      using stereological methods.
AB  - BACKGROUND: The purpose of this study was to compare different techniques for the
      estimation of spleen volume and surface area using magnetic resonance imaging
      (MRI) images, ultrasonography (USG) images and cadaveric specimen, and to
      evaluate errors associated with volume estimation techniques based onfluid
      displacement. MATERIALS AND METHODS: Five new born cadavers, aged 39.7 +/- 1.5
      weeks, weighted 2.220 +/- 1.056 g, were included in the present study. Three
      different methods were used to assess the spleen volume. The vertical section
      technique was applied using cycloid test probes for estimation of spleen surface
      area in MRI. RESULTS: The mean +/- standard deviation of spleen volumes by fluid
      displacement was 4.82 +/- 3.85 cm3. Volumes determined by the Cavalieri's
      principle using physical section and point-counting techniques were 4.45 +/- 3.47
      cm3 and 4.65 +/- 3.75 cm3, respectively; volumes measured by USG and cadaver
      using ellipsoid formula were 4.70 +/- 3.02 cm3 and 5.98 +/- 4.58 cm3,
      respectively. No significant differences were found among all methods (p > 0.05).
      The spleen surface area was calculated as a 32.3 +/- 20.6 cm2 by physical
      sections using cadaver and also it was determined on axial, sagittal and coronal
      MR planes as 24.9 +/- 15.2 cm2, 18.5 +/- 5.92 cm2 and 24.3 +/- 12.7 cm2,
      respectively. CONCLUSIONS: As a result, MR images allow an easy, reliable and
      reproducible volume and surface area estimation of normal and abnormal spleen
      using Cavalieri'sprinciple. We consider that our study may serve as a reference
      for similar studies to be conducted in future. :

PMID- 24902098
TI  - Evaluation of additional head of biceps brachii: a study with autopsy material.
AB  - Additional head of the biceps brachii (AHBB) has been reported in different
      population groups with a frequency of 1-25%. The purpose of this study was to
      determine the incidence and morphologic expression of the AHBB as determined in a
      sample of the Colombian population. An exploration was conducted with 106 arms
      corresponding to unclaimed corpses autopsied at Institute of Legal and Forensic
      Medicine of Bucaramanga, Colombia. Using medial incision involvingskin,
      subcutaneous tissue, and brachial fascia, the heads of the biceps and their
      innervating branches were visualised. One AHBB was observed in 21 (19.8%) of the
      arms evaluated, with non-significant difference (p = 0.568) per side of
      presentation: 11 (52.4%) cases on the right side and 10 (47.6%) on the left side.
      All AHBBs were originated in the infero-medial segment of the humerus, with a
      mean thickness of 17.8 +/- 6.8 mm. In 4 (19%) cases the fascicle was thin, less
      than 10 mm; in 7 (33.3%) cases it was of medium thickness, between 11 and 20 mm,
      whereas in 47.6% it was longer than 20 mm. The length of the AHBB was 118.3 +/-
      26.8 mm; its motor point supplied by the musculocutaneous nerve was located at
      101.3 +/- 20.9 mm of the bi-epicondylar line. The incidence of AHBB in this study
      is located at the upper segment of what has been reportedin the literature and
      could be a morphologic trait of the Colombian population; in agreement with prior
      studies, the origin was the infero-medial surface of the humerus. 

PMID- 24902099
TI  - Interface between intramembranous and endochondral ossification in human
      foetuses.
AB  - In the head and neck of human mid-term foetuses, the interface between areas of
      endochondral ossification and adjacent membranous (intramembranous) ossification
      is extensive. Using 8 foetal heads at 15-16 weeks, we have demonstrated
      differences in the matrices and composite cells between these 2 ossification
      processes, especially in the occipital squama and pterygoid process. Aggrecan
      positive cartilage was shown to be invaded by a primitive bony matrix that was
      negative for aggrecan. At the interface, the periosteum was continuous with the
      perichondrium without any clear demarcation, but tenascin-c expression was
      restricted to the periosteum. In contrast, the interface between the epiphysis
      and shaft of the femur showed no clear localisation of tenascin-c. Versican
      expression tended to be restricted to the perichondrium. In the pterygoid
      process, the density of CD34-positive vessels was much higher in endochondral
      than in membranous ossification. The membranous part of the occipital was
      considered most likely to contribute to growth of the skull to accommodate the
      increased volume of the brain, while the membranous part of the pterygoid process
      seemed to be suitable for extreme flattening under pressure from the pterygoid
      muscles. 

PMID- 24902100
TI  - The variant course of the suprascapular artery.
AB  - The suprascapular artery (SSA) has been identified to be of clinical relevance in
      surgical intervention and fracture healing of the shoulder. Despite the classic
      description of its course and relation to the superior transverse scapular
      ligament, it is subject to much variation. The aims of this study were: (i) to
      describe the course of the SSA in relation to the superior transverse scapular
      ligament, (ii) tob determine the prevalence of the course of the SSA in relation
      to the superior transverse scapular ligament, (iii) to determine the prevalence
      of the variant origin of the SSA in cases presenting with variant course of the
      latter, and (iv) to establish a difference in laterality and that between adults
      and foetuses. The course of the SSA was investigated through the macro- and micro
      dissection of the antero-andpostero-superior shoulder regions of 31 adult and 19
      foetal cadaveric specimens (n = 100). The SSA was observed to pass inferior to
      the superior transverse scapular ligament accompanied by the suprascapular nerve
      (20%), which corroborated the findings of previous studies. Subsequently, this
      variant course of the SSA also appeared to present with the variant origin of it
      in many instances (13%): from the 3rd part of the subclavian artery (4%), 1st
      part of the axillary artery (2%), 2nd part of the axillary artery (5%) and SSA
      (2%). Injury to the SSA may cause more serious trauma than that of arteries which
      are isolated from the great vessels, therefore the recognition and knowledge of
      variation in the origin and course of the SSA is significant in the treatment of
      diseases in the shoulder and cervical regions. Furthermore, the accompaniment of
      the suprascapular nerve with the SSA at the suprascapular notch inferior to the
      superior transverse scapular ligament may lead to neuropathy syndromes due to the
      pulsation of the artery against the nerve within the confined notch. 

PMID- 24902101
TI  - Morphology of suprascapular notch in medieval skeletons from Bulgaria.
AB  - The suprascapular notch is situated in the lateral part of the superior border of
      the scapula, just medial to the base of the coracoid process, giving passage for
      the suprascapular nerve. The aim of this study is to determine the frequency of
      different types of suprascapular notch in male and female medieval skeletal
      series and to assess the sexual differences. The shape of the notch was
      classified into 5 types, based on the scheme given by Alekseev. A total of 102
      scapulae and scapular fragments were investigated. The results show that the deep
      notch was the most common. In the left female scapulae the shallow notch was
      frequently observed as well. Three cases of suprascapular foramen, which is
      considered as a risk factor for suprascapular nerve neuropathy, were observed and
      there was a double foramen in one of them, which is a very rare case. According
      to the results of c2 test, there were no significant sexual differences in the
      distribution of notch types. Our results illustrate that there were some
      individuals among the investigated medieval population potentially affected by
      suprascapular nerve entrapment syndrome and their way of livingmay have been
      impacted by the symptoms accompanying this condition. 

PMID- 24902102
TI  - Morphology and a proposed model of innervation of the human deltoid muscle: a
      pilot study.
AB  - BACKGROUND: The deltoid muscle (DM) plays an essential role in retaining the
      stability and correct function of the upper limb. The aims of the study were to
      perform a detailed morphological analysis of the DM including its innervation,
      structure, attachments and relationship with adjacent structures. MATERIALS AND
      METHODS: The study was carried out on 17 formalin-fixed cadavericupper limbs.
      After dissection of the shoulders, the DM was visualised and analysed.The
      following measurements of the muscle were performed for all cases: width of
      attachments (acromial, clavicular, spinal), entire width of origin, length of the
      component parts (acromial, clavicular, and spinal) and length of the arm.
      RESULTS: In all specimens, a characteristic 'segmented' innervation scheme of the
      DM was observed. The axillary nerve (AN) was always divided into an anterior
      branch (abAN) and a posterior branch (pbAN). Two variations of the DM innervation
      were distinguished: variation I, where the clavicular and the acromial parts were
      innervated by the abAN, while the spinal part was supplied both by abAN (anterior
      fibres) and by pbAN (posterior fibres), and variation II, in which the spinal
      part did not have double innervation - the abAN innervation area covered only the
      acromial and clavicular parts, and the entire spinal part was supplied by pbAN.
      Both variations had a segmented arrangement of sub-branches reaching individual
      parts of the DM, which was particularly distinct in the clavicular and acromial
      parts. Correlations were found between the entire width of the DM originand the
      length of the arm (p = 0.001), between the length of the acromial part of the DM
      and the length of the arm (p = 0.003), between the width of the spinal attachment
      and the length of the spinal part (p = 0.002), and between the width of the
      spinal attachment and the length of the arm (p = 0.0008). CONCLUSIONS: The study
      confirmed the existence of a characteristic segmented innervation scheme of the
      DM which corresponds with the segmented morphology of its individual parts. An
      analysis of the internal structure of the muscle specific architectonics based on
      the tendon system was also presented.

PMID- 24902103
TI  - Trigeminal neuralgia caused by aneurysm of the posterior cerebral artery: a case
      description and the analysis of anatomical variety of vascular complex in the
      root entry zone of trigeminal nerve.
AB  - Trigeminal neuralgia is still a riddle, especially in the pathophysiology of the
      ticdouloureux, although the problem has been described in many medical
      publications. The major theory of pain based on the compression of the Vth nerve
      by tumours or vessels in the root entry zone (REZ) does not explain the facial
      pain in patient without neurovascular conflict, with multiple sclerosis or with
      conflict in places other than REZ. We report a case of the posterior cerebral
      artery aneurysm, which caused the isolated trigeminal neuralgia in a 48-year-old
      woman. She was operated on through microvascular decompression and the aneurysm
      was wrapped. In the second part of this study we review morphological variations
      of the neurovascular conflict on the basis of anatomical publications.

PMID- 24902104
TI  - An asymmetrical fenestration of the basilar artery coexisting with two aneurysms
      in a patient with subarachnoid haemorrhage: case report and review of the
      literature.
AB  - The vertebrobasilar system is a part of the cerebral arterial circle (circle of
      Willis), which forms the collateral circulation of the brain. A 75-year-old
      Caucasian female was admitted to hospital because of a strong headache radiating
      to the neck. On the basis of a neurological examination, the patient was
      classified into group III of the Hunt and Hess scale. Subarachnoid haemorrhage
      and 2 aneurysms of the cerebral arteries were diagnosed during multidetector 64
      row computed tomography and angiography. An asymmetrical fenestration of the
      proximal part of the basilar artery was also observed. The bleeding aneurysm
      locating at anterior communicating artery was diagnosed and clipped surgically by
      right fronto-parietal craniotomy. The second aneurysm was located just after the
      junction of the vertebral arteries on the wall of the basilar artery. The
      presented case firstly illustrates the asymmetric fenestration of the proximal
      part of the basilar artery coexisting with subarachnoid haemorrhage and 2
      aneurysms of brain arteries. Such observation should increase diagnostic
      attention in the detection of possible associated aneurysms and can help in
      preventing complications during all endovascular treatment procedures. 

PMID- 24902105
TI  - Common origin of left anterior descending artery and right coronary artery from
      right aortic sinus: presentation of rare variant.
AB  - The authors discuss a case of 55-year-old man admitted to hospital with clinical
      symptoms and electrocardiac signs of myocardial infarction, who underwent
      invasive diagnosis and one of most rare coronary arteries anomaly was observed:
      common origin of right coronary artery and anterior interventricular artery (left
      anterior descending artery) from right aortic sinus. Anatomical variants of
      coronary arteries are rare amongst general population, ranging between 0.29% to
      1.3% and such anomaly is found in 0.03% of all coronarographies and is
      responsible for 2.3% of all coronary variations. Knowledge about coronary
      arteries anomalies is helpful not only in making better diagnosis but also in
      making better therapeutic decisions. 

PMID- 24902106
TI  - Endocortical plating of the bandeau during fronto-orbital advancement provides
      safe and effective osseous stabilization.
AB  - BACKGROUND: Ectocortical resorbable plate fixation has become a standard method
      of fixation during fronto-orbital advancement (FOA) in young children. Plate
      hydrolysis occurs slowly and can cause visible prominences, sterile abscesses,
      and osseous depressions that can persist after complete resorption. Although
      endocortical placement avoids contour issues, the safety and effectiveness of
      this technique are undocumented. METHODS: A review of our prospectively collected
      craniofacial database was performed. All patients undergoing FOA by a single
      craniofacial team at a single institution from 1997 to 2011 were examined.
      Inclusion criteria were as follows: (1) unicoronal, bicoronal, or metopic
      synostosis; (2) resorbable endocortical fixation of the bandeau; and (3) follow
      up for 1 year or longer. Evaluation included patient demographic data,
      postoperative clinical course, and computed tomography imaging when available.
      RESULTS: Seventy-three patients met the inclusion criteria. Fusion involved the
      unicoronal (n = 26), bicoronal (n = 19), and metopic (n = 28) sutures. Mean age
      at operation was 8.3 months (range, 2.7-35.5 mo), and follow-up was 4.5 years
      (range, 1.0-9.9 y). No endocortical or ectocortical sterile abscesses were
      documented in our series. Postoperative complications included hematoma (n = 2),
      infection (n = 2), wound breakdown (n = 3), cerebral contusion (n = 2), and
      cerebrospinal fluid leak (n = 1); none of these issues were related to
      endocortical absorbable fixation. Fifty-eight patients (80%) were categorized as
      Whitaker classification I/II; and 15 patients (20%), Whitaker classification
      III/IV. Postoperative computed tomography (mean follow-up, 4.6 y) was obtained in
      34 patients (47%). All plates were completely resorbed, and there were no bone or
      soft tissue irregularities in the region where the plates were placed.
      CONCLUSIONS: Endocortical resorbable fixation is a safe and effective method of
      osseous stabilization during FOA for craniosynostosis in young children.

PMID- 24902107
TI  - Computed tomography and magnetic resonance imaging of maxillofacial lesions in
      renal osteodystrophy.
AB  - PURPOSE: This study aims to describe the computed tomography (CT) and magnetic
      resonance (MR) imaging appearance of maxillofacial lesions in renal
      osteodystrophy. PATIENTS AND METHODS: We retrospectively reviewed the CT and MR
      imaging of maxillofacial region in 9 patients (6 females and 3 males with mean
      age of 31 yr) with renal osteodystrophy. They presented with facial swelling (n =
      6), facial disfigurement (n = 2), and oral cavity mass (n = 1). They underwent CT
      and MR imaging of the maxillofacial region. RESULTS: Brown tumors (n = 6) were
      seen in the mandible (n = 4) and maxilla (n = 2). They appeared as mixed lytic
      and sclerotic (n = 4) and sclerotic (n = 2) lesions at CT. The lesions appeared
      as hypointense at T1-weighted images and of mixed signal intensity at T2-weighted
      images with intense contrast enhancement (n = 6). Uremic leontiasis ossea (n = 2)
      appeared at CT as diffuse hyperostosis with protruded maxilla and obliterated
      sinus. At MR imaging, there was expansion of the maxilla with obliteration of the
      maxillary sinuses and protrusion of the mandible. The lesion exhibited low signal
      intensity at T1-weighed images. At T2-weighted images, the lesion showed low
      signal intensity with small hyperintense lesions. Dystrophic calcification (n =
      2) was seen in the parotid and the check. CONCLUSION: We concluded that CT and MR
      imaging are helpful for diagnosis and treatment planning of maxillofacial lesions
      of patients with renal osteodystrophy.

PMID- 24902108
TI  - Total scalp reconstruction following a dog bite in a pediatric patient.
AB  - The purpose of this case report is to present the reconstruction of a full
      thickness scalp defect in a 2-year-old Hispanic male mauled by a dog, which was
      performed by a novel technique. After the scalp defect was debrided multiple
      times and treated with greater than 600 cm2 of cryopreserved human skin
      allograft, Integra was applied to the scalp defect following debridement and
      burring-out the outer bony cortex to promote bleeding and integration, followed
      by the application of a VAC dressing. Four weeks later, the mature Integra was
      grafted with split-thickness grafts. One year after the original injury, the
      patient demonstrated 98% take of the skin grafts to the calvarium. The resultant
      soft-tissue cover was supple, pliable, uniform in texture, and stable. The
      proposed technique of reconstruction of large full-thickness scalp defects in
      pediatric patients is easily reproducible, involves a short operative time, and
      produces satisfying cosmetic results.

PMID- 24902109
TI  - Successful reconstruction of irradiated anterior skull base defect using the dual
      flap technique involving local pericranial flap and radial forearm free flap.
AB  - Skull base reconstruction presents a challenging therapeutic problem requiring a
      multispecialty surgical approach and close cooperation between the neurosurgeon,
      head and neck surgeon, as well as plastic and reconstructive surgeon during all
      stages of treatment. The principal goal of skull base reconstruction is to
      separate the intracranial space from the nasopharyngeal and oropharyngeal
      cavities, creating support for the brain and providing a water-tight barrier
      against cerebrospinal fluid leakage and ascending infection. We present a case
      involving a 58-year-old man with anterior skull base defects (2.5 cm * 3 cm)
      secondary to the removal of olfactory neuroblastoma. The patient received
      conventional radiation therapy at 6000 cGy in 30 fractions approximately a month
      before tumor removal. The patient had radiation therapy before surgery and was
      planned to have postoperative radiation therapy, which would lead to a higher
      complication rate of reconstruction. Artificial dura was used for the packing of
      the dural defect, which was also suspected to increase the complication rate of
      reconstruction. For these reasons, we chose to apply the dual flap technique,
      which uses both local pericranial flap and de-epithelized radial forearm free
      flap for anterior skull base defect to promote wound healing. During 28 months of
      follow-up after coverage of the anterior skull base defect, the dual flap
      survived completely, as confirmed through follow-up magnetic resonance imaging.
      The patient was free of cerebrospinal fluid leakage, meningitis, and abscess, and
      there was minimal donor-site morbidity of the radial forearm free flap.
      Reconstruction of anterior skull base defects using the dual flap technique is
      safe, reliable, and associated with low morbidity, and it is ideal for irradiated
      wounds and low-volume defects. 

PMID- 24902110
TI  - Surgical neurolysis for the treatment of neuropathic pain in 2 postmenopausal
      women with mandibular necrosis resulting from oral bisphosphonates.
AB  - We analyze the use of surgical neurolysis for the treatment of neuropathic pain
      of the inferior alveolar nerve. For that, 3 surgical neurolysis were performed on
      2 postmenopausal women experiencing neuropathic pain of the inferior alveolar
      nerve due to mandibular necrosis resulting from treatment with oral
      bisphosphonates. Both patients showed sensory impairment of the inferior alveolar
      nerve. We obtained complete control of neuropathic pain after 6 months of the
      patients' evolution, preserving the function of the lingual nerve in all 3
      neurolysis, without causing any impact as regards to the sensitive situation
      before treatment. Surgical neurolysis of the inferior alveolar nerve may be
      considered as the choice therapeutic technique to treat neuropathic pain of this
      nerve when there is a sensory impairment in patients showing mandibular necrosis
      resulting from bisphosphonates. 

PMID- 24902112
TI  - Resection of suprasellar meningioma through interhemispheric approach.
AB  - The present study aims to discuss the value and the effect of resection of
      suprasellar meningioma through the interhemispheric approach. Twenty-nine cases
      of patients with suprasellar meningioma diagnosed through enhanced magnetic
      resonance imaging scans and postoperative histopathologic examination underwent
      resection of tumors (the largest diameter ranged from 3 cm to 6 cm) by the
      microsurgical technique of small bone window (about 5 cm * 6 cm) through the
      interhemispheric approach. Among all cases, 25 (86%) (Simpson I, II) were of
      total resection of tumors and 4 were of subtotal resection of tumors. Moreover,
      along all cases, 19 were of improved vision and view, 2 of postoperative diabetes
      insipidus, and 1 of electrolyte imbalance. No operative death occurred. The small
      bone window interhemispheric approach can be used to expose tumors, lightly
      stretch brain tissues, reduce the incidence of complications, and improve the
      total resection rate of tumors of patients with sellae meningiomas growing
      forward, upward, and into the sella. 

PMID- 24902111
TI  - Is there an association between olfactory bulb volume and the Keros type of fossa
      olfactoria?
AB  - PURPOSE: The purpose of this study was to investigate the relationship between
      the volume of the olfactory bulb (OB), the depth of the olfactory sulcus (OS),
      the depth of the fossa olfactoria (FO), and the height of the OB. METHODS: A
      total of 54 patients participated (9 women and 45 men; mean [SD] age, 27 [38] y;
      range, 20-45 y). Magnetic resonance imaging was performed with a 1.5-T system
      (slice thickness, 1 mm). Measurements of the right and left OB volumes were
      performed through manual segmentation of the coronal slices. We measured the
      depth of the FO on the basis of Keros classification on coronal magnetic
      resonance images. The depth of the OS was measured on the coronal plane at the
      posterior tangent through the orbital globes. The height of the OB was measured
      on the coronal plane of the cribriform plate at the highest portion of the OB.
      RESULTS: The mean (SD) right OB volume was measured to be 52.21 (13.73) mm3 with
      a range between 33.90 and 95.70 mm3. The mean (SD) left OB volume was measured to
      be 53.98 (13.31) mm3 with a range between 31.20 and 94.10 mm3. Type 1, type 2,
      and type 3 Keros ratios of the FO bilaterally were 12.9% (7/54), 68.5% (37/54),
      and 3.7% (2/54), respectively. There was no significant relationship between the
      OB volume and ipsilateral Keros type of FO (right side: P = 0.208; left side: P =
      0.164). Similarly, there was no significant relationship between the OB volume
      and depth of OS on both sides (right side: P = 0.073; left side: P = 0.065).
      There was no significant association between the Keros type of the right FO and
      depth of the OS (right side: P = 0.812; left side P = 0.863). CONCLUSIONS: We
      conclude that there is no statistical correlation between the OB volume and depth
      of the FO (Keros type). From the current study, it may be concluded that the
      depth of the FO may develop largely independent from OB volumes. The individuals
      without smell disorder have a wide range in OB volume. The method of OB volume
      measurement that we described is a valid measure of real OB volumes with high
      reproducibility.

PMID- 24902113
TI  - Long-term changes in the masseter muscle following reduction gonioplasty.
AB  - Many plastic surgeons use mandibular osteotomy (reduction gonioplasty) without
      masseter resection to correct a square face. However, there is not enough long
      term observation of the masseter after reduction gonioplasty, although some
      researches have already confirmed that the volume of masseter muscle does
      decrease shortly after reduction gonioplasty. METHODS: The Plastic Surgery
      Hospital database was retrospectively reviewed for patients who underwent
      reduction gonioplasty. Fifty-six patients with both preoperative and 4 years
      postoperative 3-dimensional computed tomography (3DCT) were included. The changes
      in the volume and morphology of the masseter muscle after reduction gonioplasty
      were assessed quantitatively. The 3DCT data were analyzed using Mimics 10.01
      software. RESULTS: All patients were satisfied with the outcome. No complications
      happened. There were significant differences between the preoperative and 4 years
      postoperative volume and morphology. CONCLUSION: After reduction gonioplasty, the
      masseter muscle atrophied (reduced 20.98% +/- 8.75%), especially the lower part
      of the masseter muscle in the long-term follow-up. Most patients with prominent
      mandibular angles should be treated with reduction gonioplasty without
      approaching the masseter muscle.

PMID- 24902114
TI  - Removal of infratemporal fossa foreign body under C-arm.
AB  - A 12-year-old boy presented to our emergency department after being shot in the
      face. A computed tomographic scan revealed a bullet through the posterolateral
      wall of the maxillary sinus into the right infratemporal area, just adjacent to
      the skull base. We elected transantral approach with the help of endoscopy and C
      arm. The bullet was successfully removed. Little is known on the best strategy
      for removing the infratemporal foreign body. Our experience in this case provides
      a safe and effective way for such injury. 

PMID- 24902115
TI  - Neuronavigation-guided endoscopic endonasal resection of extensive skull base
      mucormycosis complicated with cerebral vasospasm.
AB  - A 24-year-old woman presented with double vision since 6 months. Examination
      revealed left eye ptosis and bilateral abducens nerve palsy. Brain computed
      tomographic scan and magnetic resonance imaging revealed a bone-eroding mass
      lesion located in the middle skull base, occupying the posterior ethmoidal cells,
      the planum sphenoidale, the sphenoid sinus, the lateral recesses of the sphenois
      sinus, the pterygoid apexes, and the middle and lower clivus, with compression of
      the inferior wall of the cavernous sinus and the parasellar and paraclival parts
      of the internal carotid artery. The patient was operated on with extended
      endoscopic endonasal approach guided with neuronavigation. Total mass resection
      was achieved. Histopathologic examination revealed mucormycosis infectious mass.
      On postoperative day 5, the patient developed right hemiplegia, and brain imaging
      revealed left internal carotid vasospasm. After treatment, the patient improved
      and was discharged. 

PMID- 24902116
TI  - Incidental findings on preoperative computed tomography for nonsyndromic single
      suture craniosynostosis.
AB  - Although the diagnosis of nonsyndromic single suture craniosynostosis (NSSC) can
      usually be made by clinical examination, computed tomography (CT) is still
      commonly used in preoperative evaluation. This practice has been questioned in
      light of recent studies that document a small, but measurable, increased risk of
      malignancy from CT-associated radiation. The purpose of this study was to examine
      whether preoperative CT for patients with NSSC provided clinically important
      information beyond confirmation of craniosynostosis. We performed a retrospective
      analysis of all patients with NSSC undergoing cranial vault remodeling at our
      center from March 1999 to March 2011. Only patients with complete preoperative CT
      scans available for review were included. Staff pediatric neurosurgeons were
      blinded to patient diagnosis and official radiology report, analyzed the CT
      images, and documented the site of synostosis and any other findings. Of the 231
      patients, 80 met the inclusion criteria. Sites of synostosis included sagittal
      (51 patients), coronal (17 patients), metopic (11 patients), and frontosphenoidal
      (1 patient). Clinical diagnosis correlated with radiographic site of fusion in
      all patients except the patient with frontosphenoidal synostosis. Incidental
      findings were documented in more than 50% of the patients including prominent
      extra-axial cerebrospinal fluid (n = 36, 45%), ventriculomegaly (n = 5, 6.25%),
      choroid fissure cyst (n = 2), cavum septum pellucidum (n = 2), Chiari
      malformation (n = 1), and prominent perivascular space (clinically nonsignificant
      finding, n = 1). Incidental findings required additional follow-up or management
      in 5 patients (6.25%). Our findings support the use of preoperative imaging in
      this population to identify intracranial anomalies that cannot be discerned by
      clinical examination. Whereas many findings were not clinically important, some
      required additional attention.

PMID- 24902117
TI  - Isolated bilateral blowout fracture with extensive pneumatization of the
      maxillary sinuses.
AB  - The blowout fracture injuries are often associated with fractures of the
      zygomatic complex and other facial structures but can also occur in an isolated
      fashion. Isolated bilateral blowout fractures are uncommon and constitute a
      challenge with regard to both assessment and reconstruction. This article
      describes an uncommon case of isolated bilateral blowout fracture in a patient
      with extensive pneumatization of the maxillary sinuses. 

PMID- 24902118
TI  - Investigation of thermochemistry associated with the carbon-carbon coupling
      reactions of furan and furfural using ab initio methods.
AB  - Upgrading furan and small oxygenates obtained from the decomposition of
      cellulosic materials via formation of carbon-carbon bonds is critical to
      effective conversion of biomass to liquid transportation fuels. Simulation-driven
      molecular level understanding of carbon-carbon bond formation is required to
      design efficient catalysts and processes. Accurate quantum chemical methods are
      utilized here to predict the reaction energetics for conversion of furan (C4H4O)
      to C5-C8 ethers and the transformation of furfural (C5H6O2) to C13-C26 alkanes.
      Furan can be coupled with various C1 to C4 low molecular weight carbohydrates
      obtained from the pyrolysis via Diels-Alder type reactions in the gas phase to
      produce C5-C8 cyclic ethers. The computed reaction barriers for these reactions
      (~25 kcal/mol) are lower than the cellulose activation or decomposition reactions
      (~50 kcal/mol). Cycloaddition of C5-C8 cyclo ethers with furans can also occur in
      the gas phase, and the computed activation energy is similar to that of the first
      Diels-Alder reaction. Furfural, obtained from biomass, can be coupled with
      aldehydes or ketones with alpha-hydrogen atoms to form longer chain aldol
      products, and these aldol products can undergo vapor phase hydrocycloaddition
      (activation barrier of ~20 kcal/mol) to form the precursors of C26 cyclic
      hydrocarbons. These thermochemical studies provide the basis for further vapor
      phase catalytic studies required for upgrading of furans/furfurals to longer
      chain hydrocarbons. 

PMID- 24902119
TI  - Peptic ulcer disease in liver cirrhosis and chronic hepatitis: impact of portal
      hypertension.
AB  - OBJECTIVE: The pathophysiology of peptic ulcer disease (PUD) in liver cirrhosis
      (LC) and chronic hepatitis has not been established. The aim of this study was to
      assess the role of portal hypertension from PUD in patients with LC and chronic
      hepatitis. MATERIALS AND METHODS: We analyzed the medical records of 455 hepatic
      vein pressure gradient (HVPG) and esophagogastroduodenoscopy patients who had LC
      or chronic hepatitis in a single tertiary hospital. The association of PUD with
      LC and chronic hepatitis was assessed by univariate and multivariate analysis.
      RESULTS: A total of 72 PUD cases were detected. PUD was associated with LC more
      than with chronic hepatitis (odds ratio [OR]: 4.13, p = 0.03). In the univariate
      analysis, taking an ulcerogenic medication was associated with PUD in patients
      with LC (OR: 4.34, p = 0.04) and smoking was associated with PUD in patients with
      chronic hepatitis (OR: 3.61, p = 0.04). In the multivariate analysis, taking an
      ulcerogenic medication was associated with PUD in patients with LC (OR: 2.93, p =
      0.04). However, HVPG was not related to PUD in patients with LC or chronic
      hepatitis. CONCLUSION: According to the present study, patients with LC have a
      higher risk of PUD than those with chronic hepatitis. The risk factor was taking
      ulcerogenic medication. However, HVPG reflecting portal hypertension was not
      associated with PUD in LC or chronic hepatitis (Clinicaltrial number
      NCT01944878).

PMID- 24902120
TI  - "I may not say we really have a method, it is gambling work": knowledge and
      acceptability of safer conception methods among providers and HIV clients in
      Uganda.
AB  - In this qualitative study, researchers assessed knowledge, acceptability, and
      feasibility of safer conception methods (SCM; timed unprotected intercourse
      [TUI], manual self-insemination, and sperm washing) among various health care
      providers (n = 33) and 48 HIV clients with recent or current childbearing
      intentions in Uganda. While several clients and providers had heard of SCM
      (especially TUI), few fully understood how to use the methods. All provider types
      expressed a desire to incorporate SCM into their practice; however, this will
      require training and counseling protocols, sensitization to overcome cultural
      norms that pose obstacles to these methods, and partner engagement (particularly
      by men) in safer conception counseling. 

PMID- 24902121
TI  - Salmonella enterica serovar Oranienburg outbreak in a veterinary medical teaching
      hospital with evidence of nosocomial and on-farm transmission.
AB  - Nosocomial salmonellosis continues to pose an important threat to veterinary
      medical teaching hospitals. The objectives of this study were to describe an
      outbreak of salmonellosis caused by Salmonella enterica serovar Oranienburg
      within our hospital and to highlight its unique features, which can be used to
      help mitigate or prevent nosocomial outbreaks in the future. We retrospectively
      analyzed data from patients that were fecal culture-positive for Salmonella
      Oranienburg between January 1, 2006, and June 1, 2011, including historical,
      clinical, and pulsed-field gel electrophoresis (PFGE) data. Salmonella
      Oranienburg was identified in 20 horses, five alpacas, and three cows during this
      time frame, with dates of admission spanning the period from August, 2006,
      through January, 2008. We consider most of these patients to have become infected
      through either nosocomial or on-farm transmission, as evidenced by molecular
      subtyping results and supportive epidemiologic data. Interpretation of PFGE
      results in this outbreak was challenging because of the identification of several
      closely related Salmonella Oranienburg subtypes. Furthermore, a high percentage
      of cases were fecal culture-positive for Salmonella Oranienburg within 24 h of
      admission. These patients initially appeared to represent new introductions of
      Salmonella into the hospital, but closer inspection of their medical records
      revealed epidemiologic links to the hospital following the index case. Cessation
      of this outbreak was observed following efforts to further heighten biosecurity
      efforts, with no known cases or positive environmental samples after January,
      2008. This study demonstrates that a Salmonella-positive culture result within 24
      h of admission does not exclude the hospital as the source of infection, and it
      underscores the important role played by veterinary medical teaching hospitals as
      nodes of Salmonella infection that can promote transmission outside of the
      hospital setting.

PMID- 24902123
TI  - Comparative probiotic strain efficacy in the prevention of eczema in infants and
      children: a systematic review and meta-analysis.
AB  - BACKGROUND: Eczema affects 3.5% of the global population, with peak prevalence
      during infancy. Eczema has no cure, but probiotics have been suggested as a
      preventative measure. OBJECTIVE: To comprehensively analyze the impact of
      prenatal and postnatal probiotic supplementation on the prevention of infantile
      and childhood eczema. METHODS: MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials, and PubMed were searched for randomized controlled trials
      regarding probiotic usage and eczema development from 1945 to 2013. Participants
      included were 7 years old or younger with probiotic exposure in utero or below 6
      months of age and who was not diagnosed previously. RESULTS: 27 publications
      describing 16 studies assessing 10 probiotics in 2,797 participants met our
      criterion. The pooled relative risk of all the studies, 0.74 (95% confidence
      interval 0.67, 0.82), indicated that probiotic supplementation in the first
      several years of life did have a significant impact on development of eczema.
      During evaluation of the studies, heterogeneity of terms and definitions for
      similar primary and secondary outcomes were identified. CONCLUSION: The use of
      probiotic supplements during pregnancy and/or during infancy creates a
      statistically significant decline in the incidence of eczema. The heterogeneity
      of terms and definitions regarding eczema is the major limitation of these
      studies.

PMID- 24902124
TI  - An epidemiological assessment of reintegration and behavioral health risk at
      Joint Base Lewis-McCord, Washington.
AB  - Soldiers from a brigade at Joint Base Lewis-McChord, Washington, were alleged to
      have committed numerous crimes, including murder of civilians, during a recent
      deployment. This study was done to assist the command with (1) analyzing the
      climate and challenges facing redeploying Soldiers; (2) assessing behavioral risk
      at both individual and unit levels through targeted reintegration screening; and
      (3) recommending mitigating strategies to enhance current reintegration processes
      and reduce the level of high-risk behavior among Soldiers following deployment.
      The findings from this public health investigation suggest levels of risk and
      major areas of concern during the redeployment period varied across battalions
      within the brigade and that risk stratification postdeployment was not correlated
      with discernible differences in predeployment indicators. Acts of violence were
      limited to the deployment and immediate postdeployment periods and were allegedly
      perpetrated by a very small number of Soldiers. 

PMID- 24902125
TI  - Soldier, doctor, patient, customer.

PMID- 24902122
TI  - The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new
      mechanism involving activation of C-terminal Src kinase.
AB  - Haemophilus ducreyi causes chancroid, a sexually transmitted infection. A primary
      means by which this pathogen causes disease involves eluding phagocytosis;
      however, the molecular basis for this escape mechanism has been poorly
      understood. Here, we report that the LspA virulence factors of H. ducreyi inhibit
      phagocytosis by stimulating the catalytic activity of C-terminal Src kinase
      (Csk), which itself inhibits Src family protein tyrosine kinases (SFKs) that
      promote phagocytosis. Inhibitory activity could be localized to a 37-kDa domain
      (designated YL2) of the 456-kDa LspA1 protein. The YL2 domain impaired ingestion
      of IgG-opsonized targets and decreased levels of active SFKs when expressed in
      mammalian cells. YL2 contains tyrosine residues in two EPIYG motifs that are
      phosphorylated in mammalian cells. These tyrosine residues were essential for YL2
      based inhibition of phagocytosis. Csk was identified as the predominant mammalian
      protein interacting with YL2, and a dominant-negative Csk rescued phagocytosis in
      the presence of YL2. Purified Csk phosphorylated the tyrosines in the YL2 EPIYG
      motifs. Phosphorylated YL2 increased Csk catalytic activity, resulting in
      positive feedback, such that YL2 can be phosphorylated by the same kinase that it
      activates. Finally, we found that the Helicobacter pylori CagA protein also
      inhibited phagocytosis in a Csk-dependent manner, raising the possibility that
      this may be a general mechanism among diverse bacteria. Harnessing Csk to subvert
      the Fcgamma receptor (FcgammaR)-mediated phagocytic pathway represents a new
      bacterial mechanism for circumventing a crucial component of the innate immune
      response and may potentially affect other SFK-involved cellular pathways.
      IMPORTANCE: Phagocytosis is a critical component of the immune system that
      enables pathogens to be contained and cleared. A number of bacterial pathogens
      have developed specific strategies to either physically evade phagocytosis or
      block the intracellular signaling required for phagocytic activity. Haemophilus
      ducreyi, a sexually transmitted pathogen, secretes a 4,153-amino-acid (aa)
      protein (LspA1) that effectively inhibits FcgammaR-mediated phagocytic activity.
      In this study, we show that a 294-aa domain within this bacterial protein binds
      to C-terminal Src kinase (Csk) and stimulates its catalytic activity, resulting
      in a significant attenuation of Src kinase activity and consequent inhibition of
      phagocytosis. The ability to inhibit phagocytosis via Csk is not unique to H.
      ducreyi, because we found that the Helicobacter pylori CagA protein also inhibits
      phagocytosis in a Csk-dependent manner. Harnessing Csk to subvert the FcgammaR
      mediated phagocytic pathway represents a new bacterial effector mechanism for
      circumventing the innate immune response.

PMID- 24902126
TI  - Epidemiologic modeling in the Department of Defense: capability and coordination
      opportunities.

PMID- 24902127
TI  - The epidemiology of Critical Care Air Transport Team operations in contemporary
      warfare.
AB  - Critical Care Air Transport Teams (CCATTs) have evolved as a vital component of
      the U.S. Air Force's aeromedical evacuation system. Previous epidemiological
      research in this area is limited. The objective of this commentary is to
      highlight the importance of obtaining robust epidemiological data regarding
      patients transported by CCATTs. A limited epidemiological analysis was performed
      to describe CCATT patients transported during Operation Enduring Freedom and the
      waning months of Operation Iraqi Freedom. CCATT transports for the calendar year
      2011 were examined as recorded in the U.S. Transportation Command Regulating and
      Command and Control (C2) Evacuation System database. As many as 290 CCATT primary
      patient transport records were reviewed. Of these, 58.6% of patients had multiple
      injuries, 15.9% of patients had traumatic brain injury, 7% had acute coronary
      syndromes, and 24.8% of all transports were for nonbattle-related injuries. The
      most common International Classification of Disease, 9th Edition, Clinical
      Modification coded injury was bilateral lower extremity amputation (40%).
      Explosive blasts were the top mechanism of injury for patients requiring CCAT.
      The distribution of injuries and illnesses requiring CCAT appear to have changed
      compared to previous conventional conflicts. Understanding the epidemiology of
      casualties evacuated by CCATT during modern warfare is a prerequisite for the
      development of effective predeployment training to ensure optimal outcomes for
      critically ill and injured warriors. 

PMID- 24902128
TI  - Predictive visual tracking: specificity in mild traumatic brain injury and sleep
      deprivation.
AB  - We tested whether reduced cognitive function associated with mild traumatic brain
      injury (mTBI) and sleep deprivation can be detected and distinguished using
      indices of predictive visual tracking. A circular visual tracking test was given
      to 13 patients with acute mTBI (recruited within 2 weeks of injury), 127 normal
      control subjects, and 43 healthy subjects who were fatigued by 26-hour sleep
      deprivation. Eye movement was monitored with video-oculography. In the mTBI
      related portion of the study, visual tracking performance of acute mTBI patients
      was significantly worse than normal subjects (p < 0.001). In the sleep
      deprivation-related portion of the study, no change was detected between the two
      baseline measures separated by 2 to 3 weeks, but the 26-hour sleep deprivation
      significantly degraded the visual tracking performance (p < 0.001). The mTBI
      subjects had substantially worse visual tracking than sleep-deprived subjects
      that could also be identified with different visual tracking indices, indicating
      possible different neurophysiological mechanisms. Results suggest that cognitive
      impairment associated with mTBI and fatigue may be triaged with the aid of visual
      tracking measures. 

PMID- 24902129
TI  - Characterization of the effects of heat stress on the DNA-intercalating dye
      EvaGreen for potential use with the joint biological agent identification and
      diagnostic system.
AB  - Although advances in real-time polymerase chain reaction (PCR) technology and
      equipment have facilitated field research, only a limited selection of reagents
      do not require cold storage. This study explored the temperature stability of the
      commercially available DNA-intercalating dye EvaGreen after exposure to a
      spectrum of temperatures for 176 days by analyzing quantification cycle (Cq) and
      end fluorescence levels during amplification of the invA gene of Salmonella
      typhimurium. To further characterize potential dye stability, the effects of
      small differences in dye volume were examined and dye samples were subjected to
      an Air Force deployment to the Middle East. Significant differences in Cq and end
      fluorescence were found; however, the magnitude of mean Cq differences was less
      than one cycle and the magnitude of mean fluorescence differences was less than
      that attributable to a difference of 0.25 MUL of dye per 25 MUL reaction. Liquid
      EvaGreen dye may thus be stable at temperatures as high as 65 degrees C for up to
      6 months for use in real-time PCR. These results warrant further investigation by
      using liquid EvaGreen dye to adapt traditional lab-based real-time PCR assays for
      Joint Biological Agent Identification and Diagnostic System use and testing the
      assays in the field. 

PMID- 24902130
TI  - Driving difficulties among military veterans: clinical needs and current
      intervention status.
AB  - Military personnel deployed to Iraq and Afghanistan often develop mental health
      difficulties, which may manifest as problematic driving behavior. Veterans may be
      more likely to engage in risky driving and to subsequently be involved in motor
      vehicle accidents and fatalities. This article reviews literature on driving
      difficulties among military veterans and evaluates available research on the
      potential pathways that underlie risky driving behavior. Current interventions
      for problematic driving behaviors are considered, and the necessity of modifying
      these interventions to address the unique difficulties encountered by military
      veterans is highlighted. The review concludes with a discussion of clinical
      implications of these findings and identification of possible avenues for future
      research and intervention. 

PMID- 24902131
TI  - Brachial plexus injury management in military casualties: who, what, when, why,
      and how.
AB  - The Global War on Terrorism has achieved an unprecedented 90% casualty survival
      rate because of far forward surgical support, rapid transport, and body armor.
      Despite the remarkable protection body armor affords, peripheral nerve injuries
      continue to occur. The brachial plexus in particular is still susceptible to
      penetrating trauma through the axilla as well as blunt mechanisms. We report
      1,818 individuals with reported cases of peripheral nerve injury, 97 of which had
      brachial plexus injury incident from Operation Iraqi Freedom and Operation
      Enduring Freedom. We suspect that true prevalence is higher as initial focus on
      vascular and orthopedic reconstruction in complex shoulder injuries may overlook
      brachial plexus lesions. Accordingly, emergency physicians, general and
      orthopedic trauma surgeons, and vascular surgeons should all consider the
      possibility of brachial plexus and other peripheral nerve injury for early and
      appropriate referral to surgeons (plastic, orthopedic, or neurosurgical) for
      further evaluation and reconstruction. The latter group should be familiar with
      appropriate modern diagnostic and initial as well as salvage therapeutic options.

PMID- 24902132
TI  - Reproductive health access among deployed U.S. servicewomen: a qualitative study.
AB  - Servicewomen's reproductive health experiences during deployment are important
      given that the majority of women in the U.S. military are of reproductive age and
      that this population experiences a disproportionately high rate of unintended
      pregnancy. Few studies have explored women's reproductive health experiences and
      their perceived barriers and facilitators to health care access during
      deployment. From May 2011 to January 2012, we conducted 22 in-depth interviews
      with women in the U.S. military about their reproductive health experiences
      during deployment, including their access to health services. Participants
      identified a range of barriers to accessing medical care in deployment settings,
      including confidentiality concerns, lack of female providers, and health-seeking
      stigma, which were reported to disproportionately impact reproductive health
      access. Some participants experienced challenges obtaining contraceptive refills
      and specific contraceptive methods during deployment, and only a few participants
      received predeployment counseling on contraception, despite interest in both
      menstruation suppression and pregnancy prevention. These findings highlight
      several policy and practice changes that could be implemented to increase
      contraceptive access and reduce unintended pregnancy during deployment, including
      mandated screening for servicewomen's contraceptive needs before operational duty
      and at least annually, and increasing the number of female providers in deployed
      settings. 

PMID- 24902133
TI  - Investigating the correlation of the U.S. Air Force Physical Fitness Test to
      combat-based fitness: a women-only study.
AB  - The primary objective in this research involves determining the Air Force
      Physical Fitness Test's (AFPFT) predictability of combat fitness and whether
      measures within the AFPFT require modification to increase this predictability
      further. We recruited 60 female volunteers and compared their performance on the
      AFPFT to the Marine Combat Fitness Test, the proxy for combat fitness. We
      discovered little association between the two (R(2) of 0.35), however, this
      association significantly increased (adjusted R(2) of 0.56) when utilizing the
      raw scores of the AFPFT instead of using the gender/age scoring tables. Improving
      on these associations, we develop and propose a simple ordinary least squares
      regression model that minimally impacts the AFPFT testing routine. This two-event
      model for predicting combat fitness incorporates the 1.5-mile run along with the
      number of repetitions of a 30-lb dumbbell from chest height to overhead with arms
      extended during a 2-minute time span. These two events predicted combat fitness
      as assessed by the Marine Combat Fitness Test with an adjusted R(2) of 0.82. By
      adopting this model, we greatly improve the Air Force's ability to assess combat
      fitness for women. 

PMID- 24902134
TI  - Enhancing the effectiveness of the U.S. Army's participation in medical
      diplomacy: implications from a case study in Trinidad.
AB  - Medical diplomacy is a complex, yet increasingly important strategy of the U.S.
      government. In this article, we present a unique program that was jointly
      developed by the U.S. Army Reserves 807 th Medical Deployment Support Command and
      the Trinidad Ministry of Health to address the large backlog of untreated
      cataracts in Trinidad and Tobago. This partnership evolved over time, but began
      with a commitment to help address a critical public health issue as determined by
      the host country, with investment in both local capacity and attention towards
      sustainability. The 807 th Medical Deployment Support Command utilized its
      connection to the military and civilian worlds, bringing in outside expertise and
      a long-term university partner allowing for sustainability without protracted
      U.S. government support. This program resulted in multiple positive outcomes,
      including building a strong partnership with a key U.S. interest; enhancing the
      legitimacy of the Trinidadian government through the development of a sustainable
      cataract program; and providing a platform for the United States to be seen by
      the Trinidadian public in a very positive light. This new model for medical
      diplomacy may have significant benefit for both the host country and U.S.
      government, and deserves further evaluation in other contexts.

PMID- 24902135
TI  - The incidence of dental disease nonbattle injuries in deployed U.S. Army
      personnel.
AB  - BACKGROUND: In the past, the U.S. Army Reserve (USAR) and Army National Guard
      (ARNG) have exhibited lower levels of medical and dental readiness than active
      duty (AD) Soldiers when activated for deployment. OBJECTIVE: The objective was to
      compare dental disease and nonbattle injury (D-DNBI) incidence rates and describe
      the most common D-DNBI diagnoses in Army AD, ARNG, and USAR Soldiers deployed to
      Iraq (Operation Iraqi Freedom/Operation New Dawn) and Afghanistan or Kuwait
      (Operation Enduring Freedom). METHODS: Data from the Center for AMEDD Strategic
      Studies (CASS) were used to determine D-DNBI encounter rates and diagnoses for
      deployed Army Soldiers. RESULTS: "Dental Caries" was the leading diagnosis
      (10.00%) for Soldiers in both theaters. For Operation Iraqi Freedom, D-DNBI rates
      were highest in 2010 at 144.05 per 1,000 Soldiers per year (AD 135.77, ARNG
      151.39 and USAR 183.76). In comparison, D-DNBI rates in Operation Enduring
      Freedom were highest in 2012 with an overall rate of 85.77 per 1,000 Soldiers per
      year (AD 72.48, ARNG 129.38 and USAR 129.52). CONCLUSIONS: In both campaigns, the
      data suggest that ARNG and USAR Soldiers had higher D-DNBI rates when compared to
      AD Soldiers. Further investigation is needed to decrease D-DNBI rates and to
      determine risk factors that may influence D-DNBI rates among Army components
      during deployments.

PMID- 24902137
TI  - beta-Hydroxy-beta-methylbutyrate improves bone properties and attenuates the
      depression of protein synthesis during a simulated sustained operation.
AB  - OBJECTIVES: Soldiers lose muscle and bone density during sustained operations. We
      investigated the impact of beta-hydroxy-beta-methylbutyrate (HMB) on bone
      properties, muscle mass, and markers of skeletal muscle regeneration under
      simulated military sustained operations. METHODS: Male mice were divided into
      four groups (10/group): (1) ALT = ad libitum + trained (1h/d for 3 d/wk); (2)
      ALTH = ALT + HMB (0.5 g/kg BW/d); (3) C = caloric restricted (-30%) + trained
      (6h/d, 6d/wk); and (4) CH = C + HMB. Assessments included bone mineral
      density/content by dual-energy X-ray absorptiometry, muscle wet weight
      (quadriceps) and expression of selected genes regulating muscle mass and protein
      turnover. Analysis of variances were used with significance set at p < 0.05.
      RESULTS: Bone mineral content increased in the ALT group (+16%) and decreased in
      the C group (-32%). Quadriceps muscle mass was lower in C (-27%) and CH (-19%)
      compared to ALT and ALTH. Myogenin mRNA expression was higher in C than ALT, ALTH
      and CH. Protein kinase B (Akt) mRNA expression was higher in both C and CH than
      ALT and ALTH. Mammalian target of rapamycin expression was higher in CH than ALT
      and ALTH. Muscle RING-finger protein-1 expression was higher in both C and CH
      than ALT and ALTH. CONCLUSION: HMB intake improved bone properties and attenuated
      the depression of protein synthesis during a simulated sustained military
      operation.

PMID- 24902136
TI  - Military inpatient residential treatment of substance abuse disorders: the
      Eisenhower Army Medical Center experience.
AB  - Opened in 2009, the Dwight D. Eisenhower Army Medical Center Inpatient
      Residential Treatment Facility (RTF) is the largest and most well-established
      inpatient substance use disorder treatment facility in the Department of Defense.
      The RTF is a 28-day inpatient treatment program that employs evidence-based
      practices and is based on Alcoholics/Narcotics Anonymous principles that are
      incorporated with a hybrid of military daily structure regime including early
      morning physical training. Family involvement is encouraged. The RTF is staffed
      by a multidisciplinary team specializing in addictions and admits
      Active/Activated Service Members (SMs) from all Service branches, typically those
      who have failed other military/civilian substance use disorder programs. Eighty
      seven percent of SMs referred to the program successfully commenced, with
      continuous sobriety observed in over half of SMs 6 months later, and 1 year
      relapse rates comparable to other alcohol treatment programs. Limitations of our
      program evaluation efforts, lessons learned, and recommendations for the way
      ahead are shared. 

PMID- 24902139
TI  - Malaria in a returning traveler from Jamaica.
AB  - Malaria in Jamaica is a real, but uncommon entity and poses a health risk to our
      Department of Defense personnel, which should not be overlooked in returning
      travelers. Malaria in Jamaica was actually considered eradicated in the 1960s,
      but there has been a reemergence attributed to the combination of Haitian
      nationals as well as endemic Anopheles mosquitoes in the Kingston area. Our
      facility recently admitted a 33-year-old Marine who had two Emergency Department
      visits before being evaluated for malaria. He had returned from Kingston 14 days
      before presentation, which included fever, night sweats, and headache followed by
      a period of malaise prior to the next paroxysm. He was found to have a 1.5%
      parasitemia with Malaria falciparum that borders on severe malaria. Fortunately,
      he was treated effectively with atovaquone/proguanil and had a favorable outcome.
      The Center for Disease Control acknowledges that malaria is present in Jamaica,
      but only recommends mosquito avoidance without prophylaxis. This case emphasizes
      the need to consider malaria in differential diagnosis in Jamaica as well as in
      any returning travelers with fever because of broad global travel. 

PMID- 24902138
TI  - Application of a collagen-based membrane and chondroitin sulfate-based hydrogel
      adhesive for the potential repair of severe ocular surface injuries.
AB  - This study was performed to evaluate the potential of a chondroitin sulfate
      polyethylene glycol (CS-PEG) adhesive and collagen-based membrane (collagen
      vitrigel, CV) combination as a method to treat penetrating ocular injuries on the
      battlefield and to improve this method with two technologies: an antibiotic
      releasing CS-PEG adhesive and a corneal shaped CV. Burst testing using porcine
      cadaveric eyes, high-performance liquid chromatography, the Kirby-Bauer bacterial
      inhibition test, and CV implantations on the live and cadaveric rabbit eyes were
      performed. The ocular burst test showed CS-PEG adhesive could successfully repair
      5-mm to 6-mm length wounds in the corneal and corneoscleral regions but would
      require CS-PEG + CV to treat larger wounds similar to those seen on the
      battlefield. In addition, high performance liquid chromatography and the Kirby
      Bauer bacterial inhibition test presented evidence suggesting the vancomycin
      incorporated CS-PEG could inhibit Staphylococcus infection for 9 days.
      Furthermore, the curved CV showed an advantage by matching the corneal contour
      without any wrinkle formation. Although this pilot study showed a limited range
      of possible applications, we demonstrated that the combination of CS-PEG adhesive
      + CV is a promising method and the 2 technologies improve their applicability to
      the special demands of the battlefield. 

PMID- 24902140
TI  - Increased BK viremia and progression to BK-virus nephropathy following high-dose
      intravenous immunoglobulin for acute cellular rejection.
AB  - BK virus nephropathy and cellular rejection are common causes of allograft
      dysfunction in renal transplant recipients. The two can be difficult to
      distinguish on allograft biopsy and can be present simultaneously. Management of
      the patient with coexistent BK infection and rejection is complicated by the
      conflicting ideals of decreasing immunosuppression to treat the former and
      increasing immunosuppression to treat the latter. The authors present the case of
      a 57-year-old renal transplant recipient who underwent allograft biopsy 8 weeks
      post-transplant for evaluation of increased serum creatinine in the setting of BK
      viremia (BKV). Biopsy revealed Banff classification 1b acute cellular rejection,
      with insufficient evidence to diagnose BK virus-associated nephropathy. The
      patient was administered intravenous immune globulin (IVIG), with no other
      changes in immunosuppressive therapy. Plasma and urine BK increased exponentially
      following IVIG administration, and allograft function further deteriorated.
      Repeat biopsy showed overt BK viral nephropathy, and BKV and creatinine decreased
      only after reduction in immunosuppression and initiation of leflunomide. Although
      case series have suggested a potential role for IVIG in the setting of BK
      infection, further study is needed to define the safety and efficacy of this
      approach. 

PMID- 24902141
TI  - OnabotulinumtoxinA successfully used as migraine prophylaxis during pregnancy: a
      case report.
AB  - Botulinum toxin (btx) received U.S. Food and Drug Administration approval for
      migraine treatment in 2010 with a pregnancy category C. There are minimal reports
      of its usage in pregnancy with no adverse effects; however, there are no reported
      cases of usage in a known pregnancy for the successful treatment of migraines. We
      present a patient with a history of 4 to 5 migraines per week refractory to
      treatment who was subsequently controlled with btx. She initially stopped
      injections, however, her migraines increased to 5 to 6 per week while using
      standard medications for migraine treatment in pregnancy. She requested btx while
      18 weeks pregnant after which she had full resolution of her migraines. She gave
      birth to a healthy full-term girl with no neuromuscular or developmental concerns
      spanning the first 6.5 years of her life, the longest reported follow-up of an
      infant whose mother received btx while pregnant. This is the first reported case
      in the literature of a patient requesting btx injections for migraine treatment
      while knowingly pregnant. The foundation of a btx pregnancy registry, similar to
      those used for antiepileptics, would be greatly beneficial to gather more safety
      data in regard to its further usage during pregnancy. 

PMID- 24902142
TI  - Ex utero intrapartum treatment of fetal micrognathia.
AB  - BACKGROUND: Ex utero intrapartum treatment (EXIT) procedures have emerged as a
      viable option for potentially life-saving procedures in fetuses with predicted
      airway compromise at birth. The ability to maintain maternal-fetal uteroplacental
      perfusion allows for prolonged procedures in a stable fetal hemodynamic
      environment thereby avoiding neonatal hypoxemia or sequelae of an emergent
      tracheostomy. CASE: A 26-year-old female presents with a 20-week ultrasound and
      subsequent magnetic resonance imaging demonstrating severe fetal micrognathia
      (jaw index below the 5th percentile), glossoptosis, polyhydramnios, absence of a
      gastric bubble, and suspected microtia concerning for Treacher Collins syndrome.
      An EXIT procedure was completed with successful intrapartum endotracheal
      intubation with a flexible fiber-optic bronchoscope through a laryngeal mask
      airway. CONCLUSION: This case represents the first EXIT procedure completed at
      Naval Medical Center San Diego. Although this case is unique, the clinical skills
      and coordination of care required to perform this procedure are exemplified in
      our daily practice of stabilizing, transporting, and definitively treating our
      wounded warriors. The ability to work in coordination across multiple armed
      services to provide the EXIT procedure to our military families, for potentially
      life-saving procedures, is a true testament to the current state of Military
      Medicine.

PMID- 24902143
TI  - Chiari malformation type I: a neuropsychological case study.
AB  - Chiari Malformation type I (CM-I) is a congenital anomaly that occurs when the
      cerebellar tonsils protrude through the foramen magnum. Individuals with this
      condition are typically asymptomatic and the identification of the malformation
      is usually an incidental finding during the course of treating another disorder.
      This case study explores the neuropsychological sequelae of two unique cases of
      CM-I in combat veterans. Neuropsychological evaluation revealed that both
      patients demonstrated preserved general cognitive functioning but had varying
      patterns of performance on measures of visuospatial, executive functioning, and
      processing speed. In terms of affective functioning, both endorsed significant
      depressive symptomatology, but had varying patterns of severity on other
      estimates of psychiatric symptomatology. Overall, results suggest that there is
      not one pattern of cognitive and affective functioning associated with CM-I and
      that environmental and psychological rather than neurological factors should be
      considered when evaluating cognitive and affective functioning. These cases also
      highlight the need for neuropsychological evaluation in CM-I in terms of
      providing guidance for psychoeducation and psychotherapy. 

PMID- 24902144
TI  - Improvement of hospital performance through innovation: toward the value of
      hospital care.
AB  - The perspective of innovation as the strategic lever of organizational
      performance has been widespread in the hospital sector. While public value of
      innovation can be significant, it is not evident that innovation always ends up
      in higher levels of performance. Within this context, the purpose of the article
      was to critically analyze the relationship between innovation and
      performance,taking into account the specificities of the hospital sector. This
      article pulls together primary data on organizational flexibility, innovation,
      and performance from 95 hospitals in Portugal,collected through a survey, data
      from interviews to hospital administration boards, and a panel of 15 experts. The
      diversity of data sources allowed for triangulation. The article uses mixed
      methods to explore the relationship between innovation and performance in the
      hospital sector in Portugal. The relationship between innovation and performance
      is analyzed through cluster analysis, supplemented with content analysis of
      interviews and the technical nominal group. The main findings reveal that the
      cluster of efficient innovators has twice the level of performance than other
      clusters. Organizational flexibility and external cooperation are the 2 major
      factors explaining these differences. The article identifies various
      organizational strategies to use innovation in order to enhance hospital
      performance. Overall, it proposes the alignment of perspectives of different
      stakeholders on the value proposition of hospital services, the embeddedness of
      information loops, and continuous adjustments toward high-value services.

PMID- 24902145
TI  - Author's reply: To PMID 23640636.

PMID- 24902146
TI  - Authors reply.

PMID- 24902147
TI  - Hospital sharing in organ donation program.

PMID- 24902148
TI  - A fond farewell.

PMID- 24902149
TI  - Midwives fail to make it onto shortage list.

PMID- 24902150
TI  - Government funding fails to reach maternity units.

PMID- 24902151
TI  - Maternity care for Polish.

PMID- 24902152
TI  - Public versus private sector support?

PMID- 24902153
TI  - The dad deficit the missing piece of the maternity jigsaw.

PMID- 24902154
TI  - This is not goodbye, but thank you.

PMID- 24902155
TI  - Post-war midwife to bestselling author.

PMID- 24902156
TI  - How to ... perform an abdominal examination.

PMID- 24902157
TI  - Prediction of uterine rupture.

PMID- 24902158
TI  - One steward's story.

PMID- 24902159
TI  - I've got it all planned out online.

PMID- 24902160
TI  - A visit to the Vroedurouw of Amsterdam: a lesson in normal birth.

PMID- 24902161
TI  - HypnoBirthing: the art to a peaceful birth.

PMID- 24902162
TI  - A 'buddy' approach to CTG.

PMID- 24902163
TI  - Best evidence for best maternal health? The conundrum of maternity service policy
      for postnatal care.

PMID- 24902164
TI  - MDG5: the emperor's new clothes?

PMID- 24902165
TI  - A day in the life of ... a midwifery lecturer.

PMID- 24902166
TI  - Breast will always be best.

PMID- 24902167
TI  - Calls for safer maternity services. Unnecessary risks are being created,
      according to King's Fund report.

PMID- 24902168
TI  - Home births.

PMID- 24902169
TI  - Community midwives.

PMID- 24902170
TI  - ICM Congress.

PMID- 24902171
TI  - To see or not to see: should parents hold their stillborn?

PMID- 24902172
TI  - Respiratory risk following elective caesarean section.

PMID- 24902173
TI  - How to ... use automated blood pressure monitoring.

PMID- 24902174
TI  - Accessing the Internet.

PMID- 24902175
TI  - Is the picture rosy?

PMID- 24902176
TI  - 2008: the year of delivery?

PMID- 24902177
TI  - Reducing maternal mortality in Gimbie.

PMID- 24902178
TI  - Healthy families: the key to a healthy future.

PMID- 24902179
TI  - Breastfeeding: making it the norm.

PMID- 24902180
TI  - Monoamniotic twins.

PMID- 24902181
TI  - Research set to reveal birthplace safety.

PMID- 24902183
TI  - A day in the life of ... a consultant midwife.

PMID- 24902182
TI  - Return to practice: 10 years on.

PMID- 24902184
TI  - A global gathering.

PMID- 24902185
TI  - Making motherhood safer in Nepal. Maternal mortality rates are improving,
      according to a recent report.

PMID- 24902186
TI  - Holding stillborns.

PMID- 24902187
TI  - Community midwives.

PMID- 24902188
TI  - Calling Sure Start midwives.

PMID- 24902189
TI  - Reducing maternal mortality in Gimbie.

PMID- 24902190
TI  - Should midwives delay administration of syntometrine?

PMID- 24902191
TI  - Hypoglycaemia in pregnancy.

PMID- 24902193
TI  - Lost in cyberspace.

PMID- 24902192
TI  - How to ... calculate the expected date of delivery.

PMID- 24902194
TI  - RCM says 'no' to locked-in pay cuts.

PMID- 24902195
TI  - Engaging with devolution.

PMID- 24902196
TI  - Aboriginal birthing: 'women's business' in the outback.

PMID- 24902197
TI  - Bonding the French way.

PMID- 24902198
TI  - A bag for life.

PMID- 24902200
TI  - Father figure.

PMID- 24902199
TI  - Home alone--a concerning trend.

PMID- 24902202
TI  - A helping hand.

PMID- 24902201
TI  - Comfort or distress: should parents hold their stillborn baby?

PMID- 24902203
TI  - A day in the life of ... a newly-qualified midwife.

PMID- 24902204
TI  - A warm hello.

PMID- 24902206
TI  - Cord clamping.

PMID- 24902205
TI  - What polyclinics mean for midwives.

PMID- 24902208
TI  - How to ... perform venepuncture.

PMID- 24902207
TI  - Workplace bullying.

PMID- 24902209
TI  - The new RCM general secretary: an introduction.

PMID- 24902210
TI  - Formalised approach to birth care.

PMID- 24902212
TI  - Screening standards revised.

PMID- 24902211
TI  - Choice as a driver?

PMID- 24902213
TI  - Passing the baton to the next midwifery generation.

PMID- 24902214
TI  - Tetanus: a tale of two world.

PMID- 24902215
TI  - Food for thought.

PMID- 24902216
TI  - Implementing maternity matters: the pathways to success.

PMID- 24902217
TI  - The 'Productive Ward' comes to maternity services.

PMID- 24902218
TI  - Information and IT in the NHS.

PMID- 24902219
TI  - Coming soon ... the Health in Pregnancy Grant.

PMID- 24902220
TI  - A day in the life of ... a specialist midwife.

PMID- 24902222
TI  - How to ... teach the APGAR score.

PMID- 24902221
TI  - Preparation: the best line of defence.

PMID- 24902223
TI  - From midwifery to dragons' den.

PMID- 24902224
TI  - Natural childbirth vs antenatal education.

PMID- 24902225
TI  - Midwifery's crystal ball?

PMID- 24902226
TI  - Cardiac disorders in pregnancy.

PMID- 24902227
TI  - Internet broadcasting: it's a new step for education.

PMID- 24902228
TI  - A ray of light in the FGM darkness.

PMID- 24902230
TI  - Fatherhood: what's it all about?

PMID- 24902229
TI  - Lights ... camera ... action ... in maternity services.

PMID- 24902231
TI  - Campaigning for vulnerable women.

PMID- 24902232
TI  - When it all goes wrong....

PMID- 24902233
TI  - Delivering the future.

PMID- 24902234
TI  - Patient safety--working together.

PMID- 24902235
TI  - A day in the life of ... a return-to-practice midwife.

PMID- 24902236
TI  - It's all change at the RCM.

PMID- 24902237
TI  - Demands of community midwifery.

PMID- 24902238
TI  - Placement crisis.

PMID- 24902240
TI  - Calling all midwives.

PMID- 24902241
TI  - The ball's in your court.

PMID- 24902239
TI  - "Why the labour ward first? A response.

PMID- 24902242
TI  - How to ... take a mother's temperature.

PMID- 24902243
TI  - Planned home birth versus planned hospital birth.

PMID- 24902244
TI  - ISA: revision required.

PMID- 24902245
TI  - It's Free ... impartial ... it's the FSA's updated money guide.

PMID- 24902246
TI  - The real diamonds of Angola.

PMID- 24902247
TI  - Cardiac disorders: care during pregnancy, labour and the puerperium.

PMID- 24902248
TI  - Baby boom predictions: getting it right.

PMID- 24902250
TI  - Starting out ... again.

PMID- 24902251
TI  - Learning for life.

PMID- 24902249
TI  - Sexual health support for teens.

PMID- 24902252
TI  - A southern diploma versus a northern degree.

PMID- 24902253
TI  - A day in the life of ... an RCM regional officer.

PMID- 24902255
TI  - The business of being born. Former talk show host Ricki Lake produces a film on
      US birth culture.

PMID- 24902254
TI  - Midwifery in Macedonia.

PMID- 24902256
TI  - Reducing maternal mortality in Gimbie.

PMID- 24902257
TI  - Over-worked and under-paid.

PMID- 24902258
TI  - Home birth.

PMID- 24902259
TI  - The VBAC waterbirth experience in fife.

PMID- 24902260
TI  - Impact of UK relocation on maternal health behaviours.

PMID- 24902261
TI  - How to ... wash your hands.

PMID- 24902262
TI  - A guide to social networking.

PMID- 24902263
TI  - Pay rates 2008: moving forward.

PMID- 24902264
TI  - Working as a VSO volunteer in Indonesia.

PMID- 24902265
TI  - Cord blood banking: the facts.

PMID- 24902266
TI  - Birthing alone: a concern for midwives?
AB  - The purpose of the two articles has been to provoke thoughts around the issues of
      supporting women who request a birth experience that challenges the norm. In the
      present climate of choice, midwives and obstetricians are falling short of
      providing the support that some women are requesting and who feel coerced into
      giving birth alone. We want to see a close in the gap between women, midwives,
      SOMs and obstetricians for all to work together to ensure that the risks and
      benefits of choice are provided and documented in a way that is legally adequate
      and desirable to women.

PMID- 24902267
TI  - Mid-husband?

PMID- 24902268
TI  - Buoyantly optimistic?

PMID- 24902271
TI  - Caffeine link to miscarriage.

PMID- 24902269
TI  - A day in the life of ... an independent midwife.

PMID- 24902270
TI  - Tetanus jab for millions.

PMID- 24902272
TI  - Maternity services benchmarked. The Healthcare Commission assesses 148 NHS Trusts
      in England.

PMID- 24902273
TI  - Breech birth.

PMID- 24902275
TI  - Doulas.

PMID- 24902276
TI  - Help wanted.

PMID- 24902277
TI  - A day for the future: Montrose student day.

PMID- 24902279
TI  - Health and safety rights.

PMID- 24902278
TI  - Risks and benefits associated with caesarean delivery.

PMID- 24902280
TI  - Lessons from an elective.

PMID- 24902281
TI  - How to ... measure blood pressure.

PMID- 24902282
TI  - Money: a free guide for parents.

PMID- 24902283
TI  - Stop smoking in pregnancy: one trust's answer.

PMID- 24902284
TI  - A smart start.

PMID- 24902285
TI  - Maternity services: ever-decreasing circles?

PMID- 24902286
TI  - A day in the life of ... Scottish social midwifery.

PMID- 24902287
TI  - The RCM opens its doors to maternity support workers.

PMID- 24902288
TI  - RCM opens its doors to MSWs.

PMID- 24902289
TI  - How to ... teach posture, handling and lifting in pregnancy.

PMID- 24902290
TI  - The pressure is too much.

PMID- 24902291
TI  - Midwives making a difference.

PMID- 24902292
TI  - Cord clamping and third stage management.

PMID- 24902293
TI  - Big Brother's big mother.

PMID- 24902294
TI  - Needs of families with a Down's syndrome baby.

PMID- 24902296
TI  - Pregnant and redundant. What can midwives do?

PMID- 24902295
TI  - When food becomes the enemy.

PMID- 24902297
TI  - Supporting breastfeeding.

PMID- 24902298
TI  - The GS tackles government policy.

PMID- 24902299
TI  - The world needs midwives now more than ever.

PMID- 24902300
TI  - Postnatal depression in Ancient Greece.

PMID- 24902301
TI  - Workplace warning for midwives.

PMID- 24902302
TI  - E-library for Scottish midwives.

PMID- 24902303
TI  - Breastfeeding saves mothers' lives.

PMID- 24902304
TI  - What? No midwifery society?

PMID- 24902305
TI  - A day in the life of ... a home birth lead.

PMID- 24902306
TI  - The global health worker crisis.

PMID- 24902307
TI  - How to ... teach pelvic floor muscle exercises.

PMID- 24902308
TI  - Hospital versus home births.

PMID- 24902309
TI  - Teach yourself breastfeeding.

PMID- 24902310
TI  - The NMC ... under the microscope.

PMID- 24902312
TI  - The Green Party's maternity policies.

PMID- 24902311
TI  - Stopping smoking and pregnancy outcomes.

PMID- 24902314
TI  - Scotland's pathway says 'no' to intervention.

PMID- 24902313
TI  - Revising the NHS's on-call arrangements.

PMID- 24902315
TI  - Maternal obesity: a growing problem.

PMID- 24902316
TI  - Funding = learning opportunities.

PMID- 24902317
TI  - New arrangements for payment by results.

PMID- 24902318
TI  - Smoking a childhood addiction.

PMID- 24902319
TI  - In the dock: threat of litigation.

PMID- 24902321
TI  - Work woes? Tribunal procedures have changed.

PMID- 24902320
TI  - Lack of healthcare information--a hidden killer.

PMID- 24902322
TI  - A day in the life of ... a maternity support worker.

PMID- 24902323
TI  - A tried and true advocate: SCMA President Andrew J. Pate, MD 2012-2013.

PMID- 24902324
TI  - Let us rise to the occasion.

PMID- 24902325
TI  - Surgical management of cricopharyngeal disorders at MUSC as compared to statewide
      trends.

PMID- 24902326
TI  - Sexual health disparities in a pregnant population in Columbia, South Carolina.

PMID- 24902327
TI  - Masked pernicious anemia: a literature review and case presentation.

PMID- 24902328
TI  - An overview of sports concussion.

PMID- 24902329
TI  - Cognitive therapy at the end of life.

PMID- 24902330
TI  - Letter to the editor.

PMID- 24902331
TI  - Calling on physicians for statewide regulatory reform.

PMID- 24902332
TI  - [Approach of new project (genetics inspection series)].

PMID- 24902333
TI  - [Chronic anemia, neutropenia and peculiar bone change seen in total parenteral
      nutrition].

PMID- 24902334
TI  - [Proposal to young pediatric neurologists--thinking about the future by
      reflecting the past (discussion)].

PMID- 24902336
TI  - [Neocortical histogenesis and intractable epilepsy].

PMID- 24902335
TI  - [Intrathecal baclofen treatment for spasticity in childhood . initial report of
      long-term follow up in Japan].
AB  - OBJECTIVE: Initial outcome of intrathecal baclofen (ITB) treatment in Japan is
      being reported on. METHODS: Chronological change of the Ashworth scale and
      complications after surgery were analyzed. Data were obtained from 71 children
      with severe spasticity who had received ITB screening tests by the end of March
      2012. RESULTS: Pump implantations for ITB treatment were performed in 43 children
      out of 62 whose spasticity reduced after baclofen injection at the screening
      tests. Postoperative evaluations of ITB treatment were carried out within one
      year and, in some cases, more than 2 years after surgery. Complications related
      to baclofen were reported on 19 occasions in 12 children within one year of ITB
      pump implantation, and on 9 occasions in 4 children of the 21 who were followed
      for more than 2 years. Main complications were hypertonia of muscle, liver
      dysfunction, and low blood pressure. The frequency of complications was lower
      than that reported previously. There was no apparent evidence to indicate that
      complications developed more in children than in adults in this study. The
      postoperative values of Ashworth scale in the upper and lower extremities were
      reduced markedly when compared with preoperative levels, and the improvements
      were statistically significant (P < 0.05). CONCLUSIONS: This is the first report
      of outcome of ITB for severely disabled children with spasticity in Japan. It was
      confirmed that ITB for children with severe spasticity is a safe and effective
      treatment.

PMID- 24902337
TI  - [Molecular genetics of intractable epilepsies].

PMID- 24902338
TI  - [Role of immunity in the pathophysiology of intractable epilepsy-postencephalitic
      epilepsy & immunity].

PMID- 24902340
TI  - [Problems of a support in severely handicapped persons with medical care after a
      revision of the Public Nursing Care Insurance Law].

PMID- 24902339
TI  - [Electrophysiology of intractable childhood epilepsy].

PMID- 24902341
TI  - [Joint researches supported by Japanese Society of Child Neurology (JSCN) the
      committee of joint researches].

PMID- 24902343
TI  - [Practical seminar on the present status and problems of compensation system for
      birth troubles].

PMID- 24902342
TI  - [Strategy of advanced research in the field of acute encephalopathy in
      childhood].

PMID- 24902344
TI  - [Effects of reading difficulties on scholastic self-evaluation and mental health
      in elementary school children].
AB  - OBJECTIVE: We aimed to examine the effects of reading difficulties on scholastic
      self-evaluation and mental health in elementary school students. METHODS:
      Following guidelines for diagnosing reading disorders in elementary school
      students, we administered reading test batteries consisting of single sounds,
      single words, and single sentences to 41 fifth-grade elementary school students
      in Japan. The students' levels of scholastic self-evaluation, self-esteem, and
      depressive symptoms were assessed using self-rating questionnaires. RESULTS: By
      evaluating students' reading speed and the number of reading errors they made, we
      found that six students (14.6%) had reading difficulties (RD group) as per the
      guidelines for diagnosing reading disorders. The scholastic self-evaluation
      scores of this RD group were significantly lower than that of the non-RD group.
      No significant differences were found between the groups on self-esteem or
      depressive symptoms scores, which we considered to be indicators of mental
      health, Speed in reading single sounds and single words, and the number of
      reading errors in reading single sounds had significant negative correlations
      with scholastic self-evaluation scores. CONCLUSION: We found that reading
      difficulties might result in decreased scholastic self-evaluation in elementary
      school students; however, reading difficulties did not directly influence self
      esteem or depression.

PMID- 24902345
TI  - [Clinical manifestations of Menkes disease vary according to patient's genotype
      and the initiation time of treatment with copper-histidine injections].

PMID- 24902346
TI  - [Moving away from nursing care by the minute].

PMID- 24902347
TI  - [The effect of corticosteroids in children and adolescents after tonsillectomy in
      the prevention of postoperative nausea and vomiting, pain and bleeding].
AB  - Tonsillectomy and adenotomy are the most common pediatric surgical procedures,
      with approximately five millions performed each year worldwide (O'Mathuna, Wiffen
      & Conlon, 2010). However, this procedure is accompanied by significant
      postoperative morbidity, which may include postoperative pain, postoperative
      nausea and vomiting (PONV), poor oral intake with consequent dehydration and
      postoperative bleeding (Hanasono et al., 2004). If pain is not treated
      effectively, it can cause avoidance behaviors related to further healthcare.
      Inadequate pain management has been found to increase morbidity and mortality
      rates in postoperative patients of all ages (O'Mathuna, Wiffen & Conlon, 2010).
      In addition, there is an increase in the incidence of PONV: 40% in children with
      pain compared to 16% in children without pain. PONV also disturbs significantly
      the wellbeing and patient satisfaction, it can lead to a substantial prolongation
      of time in the recovery room with increased costs of personal care. In pediatric
      patients PONV is the most common cause of the approximately 1% to 2% of unplanned
      hospitalizations following outpatient surgery (Rusch et al., 2010). The incidence
      of bleeding after tonsillectomy is approximately 0.5-10%, with deaths occurring
      in 1 in 20,000 patients (Kim et al., 2011). In recent years, several scientists
      have explored the effect ofcorticosteroids in the reduction of morbidity after
      tonsillectomy. In this publication, the question is addressed to what extent
      perioperatively administered corticosteroids can reduce pain, PONV and
      postoperative bleeding in the context of tonsillectomy in children and
      adolescents. For this purpose, a narrative literature analysis of the electronic
      databases and journals was conducted. There is evidence that corticosteroids can
      reduce postoperative morbidity. However, no evident and clear recommendation can
      be drawn from the advices of the various studies.

PMID- 24902348
TI  - [End of life care in intensive care medicine].

PMID- 24902350
TI  - [Inquiry. Supplementary food for baby].

PMID- 24902349
TI  - [Child welfare and will of the child in medicine: an ethical analysis].

PMID- 24902351
TI  - [5 years Balthasar youth hospice].

PMID- 24902352
TI  - ["Time to laugh e.V." visits children in the LMU Uniclinic on the Grosshadern
      Campus. With many entertainers the "Time to Laugh" Organization provides variety
      in the daily clinic routine ].

PMID- 24902353
TI  - [Continued increase in the number of homeless families].

PMID- 24902354
TI  - [It is high time: "Save the pediatric clinics"].

PMID- 24902355
TI  - [The value of postpartal care of moderately impaired newborn infants].

PMID- 24902356
TI  - [Too much water hurts the skin. BWG: protecting hands at work and at home from
      moisture].

PMID- 24902357
TI  - [Multipliers continuing education. Infant nutrition].

PMID- 24902358
TI  - Contemporary update on pathology-related issues on routine workup of prostate
      biopsy: sectioning, tumor extent measurement, specimen orientation, and
      immunohistochemistry.
AB  - While the prime goal of the needle biopsy is to diagnose prostatic adenocarcinoma
      (PCa), once PCa is detected further descriptive information regarding the type of
      cancer, amount of tumor, and grade in prostate needle cores forms the cornerstone
      for contemporary management of the patient and to assess the potential for local
      cure and the risk for distant metastasis. This review gives an update on selected
      pathology-related issues on routine workup of prostate biopsy with special
      references to adequate histologic sectioning necessary to maximize cancer yield,
      tumor extent measurements and methodologies, specimen orientation, and the role
      of immunohistochemistry in the evaluation of the prostate. Multiple factors
      influence the diagnostic yield of prostate biopsies. Many of these factors are
      fixed and uncontrollable. Other factors are controlled by the urologist,
      including number of cores obtained, method and location of biopsy, and amount of
      tissue obtained. The yield of cancer is also controlled by the pathologist and
      histotechnologist. It is necessary to report the number of cores submitted and
      the number of positive cores, thereby giving the fraction of positive cores. The
      percentage involvement by carcinoma with or without the linear extent of
      carcinoma of the single core with the greatest amount of tumor should also be
      provided. Using the marking technique, we can add a new pathological parameter:
      pathological orientation. Cancer or atypical lesions can be accurately located
      within the biopsy specimen and integrated to biopsy approach. Probably the most
      common use of immunohistochemistry in the evaluation of the prostate is for the
      identification of basal cells, which are absent with rare exception in
      adenocarcinoma of the prostate and in general positive in mimickers of prostate
      cancer. If a case is still considered atypical by a uropathology expert after
      negative basal cell staining, positive staining for alpha-methylacyl-CoA-racemase
      can help establish in 50% of these cases a definitive diagnosis of cancer.

PMID- 24902359
TI  - Focal prostatic atrophy: morphologic classification and immunohistochemistry.
AB  - OBJECTIVE: To describe the morphology of focal prostatic atrophy and propose a
      comprehensive histologic classification for a proper diagnostic recognition.
      STUDY DESIGN: A broad immunohistochemical study was performed as an adjunct to
      its recognition as well as a contribution to pathogenesis. RESULTS: A morphologic
      continuum was seen on needle biopsies. Chronic inflammation was present only in
      complete atrophy. Immunohistochemical findings in partial atrophy are similar to
      normal acini. Luminal compartment in complete atrophy shows aberrant expression
      of 34betaE12 favoring an intermediate phenotype. ERG negativity in all variants
      of atrophy may have value in the identification of the lesion. CONCLUSION: The
      morphologic findings favor a continuum probably partially preceding complete
      atrophy. Chronic inflammation may be a secondary phenomenon seen only in complete
      atrophy. Overexpression in complete atrophy of glutathione S-transferase pi
      relates to oxidative stress possibly related to chronic ischemia, of c-Met favors
      the concept that intermediate cells may be target for carcinogenesis, and of CD44
      may be related to the recruitment of inflammatory cells.

PMID- 24902360
TI  - Comparative analysis of gene expression profiles in basal-like carcinomas of the
      breast.
AB  - OBJECTIVE: To compare basal-like breast carcinoma (BLBC) gene expression profiles
      to normal mammary epithelium in order to determine the characteristic gene
      expression patterns associated with the tumor. STUDY DESIGN: The gene expression
      profiles of 12 cases of BLBC were analyzed using a human mRNA genome expression
      profiling chip containing 48,804 probes in an attempt to characterize molecular
      mechanism involved in the carcinogenesis of BLBC. RESULTS: The identified 99
      genes were upregulated more than fourfold fold-change (FC) value over their
      levels in normal mammary ductal epithelial cells, and 43 genes were downregulated
      to less than fivefold FC value compared to normal epithelial cells. Verification
      of selected genes by semiquantitative reverse transcription polymerase chain
      reaction was performed to confirm the expression data obtained by microarray
      analysis. Most of the abnormal expressed genes were related to DNA binding,
      transcription and its factor, cell receptors, cell signals and transmitted
      proteins, metabolism-related proteins, and protein synthesis-related genes.
      CONCLUSION: The difference of gene expression profiles might be of benefit for
      selecting the relative genes of the basal-like carcinoma as the therapy target
      and to further the understanding of the development of BLBC.

PMID- 24902361
TI  - Topological features of erythrocytes in thalassemic patients: quantitative
      characterization by scanning electron and atomic force microscopy.
AB  - OBJECTIVE: To examine the efficiency of scanning electron microscopy (SEM) and
      atomic force microscopy (AFM) in investigating structural anomalies of
      thalassemic erythrocytes. STUDY DESIGN: Erythrocytes or red blood cells (RBCs)
      separated from blood samples of 35 healthy and 42 thalassemic individuals were
      processed for SEM and AFM imaging, respectively. SEM images were taken after
      erythrocytes fixed on cover slips were coated with gold. Alterations in both 2D
      and 3D surface features of erythrocytes were examined with AFM in tapping mode.
      Fractal dimension was used to estimate erythrocytes surface roughness from SEM
      and AFM images. RESULTS: SEM and AFM images showed that healthy erythrocytes were
      uniform, exhibiting a typical circular and biconcave shape. Thalassemic
      erythrocytes were notably smaller and the central part was swollen, resulting in
      irregularity. In the case of SEM images it was observed that there was
      significant increase (p < 0.001) in roughness of thalassemic erythrocytes.
      Surface roughness parameters of thalassemic erythrocytes in AFM images were
      significantly higher (p < 0.001) as compared to healthy ones. CONCLUSION: Surface
      characteristics of erythrocytes are important determinants for distinguishing
      thalassemic RBCs. Both SEM and AFM images revealed morphological deformities of
      thalassemic erythrocytes. AFM proved to be a powerful technique for topographical
      characterization of abnormal erythrocytes.

PMID- 24902362
TI  - Toll-like receptor 2 and P. acnes: do they trigger initial acne vulgaris lesions?
AB  - OBJECTIVE: To elucidate the role of toll-like receptor 2 (TLR2) in the
      pathogenesis of acne vulgaris through its immunohistochemical localization in
      inflammatory and noninflammatory lesions of this disease entity. STUDY DESIGN:
      Using standard immunohistochemical techniques, we examined 30 acne cases
      (involved and noninvolved skin) and the normal skin biopsies of 30 sex- and age
      matched, healthy subjects representing the control group. RESULTS: All examined
      cases showed positive TLR2 expression in epidermis, pilosebaceous units and
      dermal inflammatory infiltrate. There were statistically significant differences
      between acne-involved skin and normal skin and between acne-involved and
      noninvolved skin regarding TLR2 expression intensity in pilosebaceous units (p <
      0.001 for both) and dermal inflammatory infiltrate (p < 0.001 for both). Intense
      TLR2 expression was in favor of inflammatory acne lesions in pilosebaceous units
      (p = 0.03) and dermal inflammatory infiltrate (p < 0.05). Intense TLR2 expression
      was also in favor of severe acne lesions in pilosebaceous units (p = 0.0002) and
      dermal inflammatory infiltrate (p = 0.001). CONCLUSION: TLR2 is involved in the
      pathogenesis of inflammatory and noninflammatory acne lesions. This occurs
      through Propionibacterium acnes-mediated activation with the resultant release of
      inflammatory cytokines.

PMID- 24902363
TI  - Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the
      ureter: a case report.
AB  - BACKGROUND: Sarcomatoid urothelial cell carcinoma of the urinary tract has a poor
      prognosis. Most of the reported cases of sarcomatoid urothelial cell carcinomas
      are those from the urinary bladder. A limited number of these tumors originate
      from the ureter. CASE: We describe a ureteral sarcomatoid urothelial carcinoma in
      a 63-year-old man who underwent nephroureterectomy with bladder cuff. The
      malignant epithelial elements consisted of undifferentiated polygonal cells and
      areas of glandular formation. Urothelial carcinoma in situ was present in the
      overlying mucosa. The mesenchymal components were pleomorphic spindle cells and
      atypical chondrocytes within lacunae with multinucleation and mitoses. The tumor
      extended beyond the muscularis into the periureteral adipose tissue. The tumor
      recurred after 6 months in the retroperitoneum and presacral area. The patient
      received chemotherapy and radiotherapy but died 16 months after the initial
      diagnosis. CONCLUSION: Sarcomatoid urothelial carcinoma of the ureter is
      uncommon. Even rarer is the presence of malignant heterologous elements such as
      chondrosarcoma. The case described here underscores the aggressive nature of
      these neoplasms.

PMID- 24902364
TI  - Osseous metaplasia within a urothelial bladder cancer nodal metastasis: a case
      report.
AB  - BACKGROUND: Osseous metaplasia within bladder cancer is extremely rare and, to
      our knowledge, has not been previously reported within a urothelial bladder
      carcinoma (UBC) nodal metastasis. CASE: A 78-year-old man underwent radical
      cystoprostatectomy because of high-grade pT2 UBC. Pathology revealed a high-grade
      pT4aN2 UBC with osseous metaplasia into a massively metastatic lymph node but not
      into the primary bladder tumor. CONCLUSION: Based independently on its location,
      this finding warrants a careful differential diagnosis with sarcomatoid bladder
      tumors and is likely to be a marker of tumor aggressiveness, thus recommending
      aggressive treatment.

PMID- 24902365
TI  - Contemporary update on pathology-related issues of adult renal neoplasms.
AB  - This review gives an update on selected issues on renal neoplasia with special
      references to emerging new tumor entities (thyroid-like follicular renal cell
      carcinoma, succinic dehydrogenase B deficiency-associated renal cell carcinoma,
      and anaplastic lymphoma kinase [ALK] translocation renal cell carcinoma), tumor
      grading (the International Society of Urological Pathology grading system), and
      assessment of tumoral involvement of the renal sinus structures, including the
      sinus fat, the loose connective tissue, or any sinus-based endothelium-lined
      space.

PMID- 24902366
TI  - Ultrasound-guided endoscopic fine needle aspiration cytology in pancreatic
      lesions: a series of 43 cases with histologic correlation from a single
      institution.
AB  - OBJECTIVE: To describe the usefulness of endoscopic ultrasound-guided fine needle
      aspiration cytology (EUS-FNAC) in pancreatic lesions. STUDY DESIGN: During a 5
      year period (2007-2011) a total of 391 patients with pancreatic lesions have been
      studied using EUS-FNAC, with 43 of them having cytohistological correlation with
      core biopsy or surgical specimens. The diagnostic performance of this technique
      with and without the pathologist in the endoscopy room has been compared.
      RESULTS: On the cytological smears, adenocarcinoma was diagnosed in 13 (30.2%)
      cases and neuroendocrine neoplasm in 2 (4.6%). Six (13.9%) cases were considered
      suspicious for malignancy, 2 (4.6%) were solid pseudopapillary tumors, and 20
      (46.5%) were negative. There were no mucin-producing cystic neoplasms in the
      cytological diagnostic approach. After the cytohistological correlation, 23
      (53.5%) cases were true positive, 11 (25.5%) were true negative, and 9 (21%) were
      false negative. There were no false positive cases in the series. Diagnostic
      precision was 79%, sensitivity 71.18%, specificity 100%, positive predictive
      value 100%, and negative predictive value 55%. The diagnostic performance of this
      technique is significantly higher (p < 0.015) when the pathologist is present in
      the endoscopy room. CONCLUSION: Our data support the usefulness and reliability
      of EUS-FNAC in the diagnosis of pancreatic lesions. In our experience,
      significantly better results are obtained when the pathologist takes an active
      part in the procedure.

PMID- 24902367
TI  - Increased dysferlin expression in Duchenne muscular dystrophy.
AB  - OBJECTIVE: To investigate dysferlin expression in muscle biopsies from patients
      with Duchenne muscular dystrophy (DMD). Dysferlin is known to have a role in the
      process of membrane fusion and muscle membrane repair in skeletal muscle fibers.
      STUDY DESIGN: We analyzed 20 muscle biopsy samples of DMD patients with
      immunohistochemical techniques to determine the expression of dysferlin.
      Immunoblotting was performed to assess dysferlin abundance in dystrophic muscle.
      RESULTS: Dysferlin showed various immunostaining patterns in dystrophic muscle,
      including reduced, normal, or enhanced sarcolemmal expression and intracellular
      immunostaining of the protein. Immunoblotting revealed that dysferlin was
      upregulated in 15 out of the 20 samples (75%). The abundance of the protein was
      analogous to the number of fibers with enhanced sarcolemmal expression of the
      protein. CONCLUSION: These data suggest that although dysferlin is not an
      integral part of the dystrophin-glycoprotein complex, its expression is altered
      in Duchenne muscular dystrophy.

PMID- 24902368
TI  - Correlation between the presence of KRAS mutation and the morphometric
      characteristics of colorectal carcinoma cell nuclei.
AB  - OBJECTIVE: To determine whether there is an association between KRAS status and
      changes in nuclear morphometric properties. STUDY DESIGN: A total of 60 cases
      were included in the analysis. Thirty cases carried a mutated KRAS oncogene,
      while 30 bore a wild-type KRAS gene. Computerized morphometry was used to measure
      various nuclear indices of size, shape, and texture. RESULTS: Nuclear ellipticity
      (p = 0.02) and chromatin textural contrast (p = 0.02) were both significantly
      higher in the mutated KRAS group. However, chromatin contrast was the only
      independent predictor of KRAS status. A ROC analysis detected a best chromatin
      contrast cutoff point of 798, with a sensitivity of 89.7% and a specificity of
      52%. Tumor grade was also associated with nuclear ellipticity (p = 0.001). Yet,
      no association was found between tumor grade and KRAS status. CONCLUSION: Our
      results suggest that the presence of a KRAS mutation in colorectal carcinoma is
      associated with alterations in the nuclear morphometric properties of contrast
      and ellipticity.

PMID- 24902369
TI  - Mast cells and angiogenesis in wound healing.
AB  - OBJECTIVE: To investigate the role of mast cells and vascular endothelial growth
      factor (VEGF) as a mediator of angiogenesis to promote wound healing in surgical
      and pathological scars. STUDY DESIGN: The study was carried out on 40 patients
      who presented with active scar lesions. They were subdivided into 4 groups. They
      included granulation tissue (10 cases), surgical scar (10 cases), hypertrophic
      scar (10 cases), and keloid scar (10 cases). Also 10 healthy volunteers of the
      same age and sex were selected as a control group. Skin biopsies were taken from
      the patients and the control group. Skin biopsies from clinically assessed
      studied groups were processed for routine histology and embedded in paraffin.
      Four sections were prepared from each paraffin block. The first section was
      stained with hematoxylin and eosin for histological evaluation. The second and
      third sections were processed for immunostaining of mast cells that contain
      chymase (MCCs) and mast cells that contain tryptase (MCTs). The fourth section
      was processed for immunostaining of VEGF. RESULTS: MCCs exhibited mild expression
      in normal tissue, granulation tissue, and surgical, hypertrophic and keloid
      scars. MCTs exhibited mild expression in normal tissue, granulation tissue and
      keloid, whereas moderate expression was exhibited in hypertrophic and surgical
      scars. VEGF expression was absent in normal tissue, mild in keloid, surgical and
      hypertrophic scars, and moderate in keloids and granulation tissue. CONCLUSION:
      Mast cell expression variation among different scar types signals the
      pathological evolution of the lesion, and hence may guide the need for
      therapeutic intervention.

PMID- 24902370
TI  - Indican from Anil (Indigofera suffruticosa Miller) as an herbal protective agent
      to the liver.
AB  - OBJECTIVE: To investigate the antitumor activity of mice bearing sarcoma 180 cell
      lines treated with indican of Indigofera suffruticosa and the histological and
      morphometric analysis on the liver of those animals. STUDY DESIGN: The mice were
      divided into 3 groups: Group 1 (G1) and Group 3 (G3) bearing sarcoma 180, and
      Group 2 (G2) without sarcoma 180. G1 and G2 (controls) were administered saline;
      G3 was treated with indican (25 mg/kg, i.p.). RESULTS: The purified indican after
      subchronic treatment did not significantly reduce the mean volume of sarcoma 180
      when compared with control G1. HistopathologicaI and morphometric analysis of the
      liver of G2 and G3 did not show degenerated areas, compared to. G1 which showed
      pronounced destruction of the liver architectures. CONCLUSION: The results showed
      that the inhibition of solid tumor growth was not significant; however, the
      indican from leaves of I. suffruticosa preserved the liver architectures,
      suggesting its use as an alternative protective agent of the liver tissue.

PMID- 24902371
TI  - Renal metastasis from thyroid carcinoma: a case report.
AB  - BACKGROUND: Renal metastases of thyroid carcinomas occur rarely and represent
      about 3% of all metastases to the kidney, with only 23 single case study reports
      in the English language literature. CASE: A 77-year-old man presented with gross
      hematuria. CT scan showed a posterior and cortico-sinusal mass in the right
      kidney measuring 5 x 3 cm. On gross examination the kidney was occupied by a
      lobulated mass measuring 4.5 cm in its greatest dimension. Microscopically, there
      was a papillary and follicular proliferation with colloid-like materials in the
      intrafollicular space. The strong positive immunohistochemical stain of
      thyroglobulin and thyroid transcription factor-1 confirmed the origin of thyroid
      gland and the diagnosis of renal metastasis of thyroid carcinoma. CONCLUSION:
      Although rare, the renal metastasis of a thyroid carcinoma is a diagnostic to
      consider even if the renal mass is unilateral and the patient has no history of
      thyroid surgery. The main differential diagnostic is the primitive thyroid-like
      follicular carcinoma of the kidney. Immunohistochemistry often leads to the right
      diagnosis, which is crucial for the management of the patient. Renal metastases
      of thyroid carcinomas are rare and often present as a primitive unilateral renal
      mass.

PMID- 24902372
TI  - Massive bilateral adrenal metastatic melanoma of occult origin: a case report.
AB  - BACKGROUND: Adrenal gland involvement by metastatic melanoma can be found in up
      to 50% of patients with ocular or cutaneous melanomas. Since these tumors are not
      hormone secreting, they usually present with locally advanced disease. CASE: We
      report on the presence of a bilateral massive metastatic adrenal melanoma in an
      80-year-old, symptomatic woman with the initial clinical diagnosis of adrenal
      hemorrhage/carcinoma. Histological assessment of the bilateral adrenalectomy
      showed a massive malignant melanoma in the adrenal glands, consistent with
      metastasis. Following that diagnosis, thorough studies revealed no ocular,
      mucocutaneous or primary tumor. The presence of melanoma in both adrenal glands
      favors metastatic melanoma over a primary adrenal melanoma. CONCLUSION: What
      makes this case rare is the unusually great size of the symptomatic bilateral
      malignant melanoma adrenal metastasis of occult primary with wide hemorrhagic and
      necrotic areas, which was probably responsible for the patient's acute symptoms.
      The search for the primary tumor may be exigent, and it might not even be present
      at the time of diagnosis. Confirmation at autopsy is advisable, however this may
      not always be feasible.

PMID- 24902373
TI  - Primary extragastrointestinal stromal tumor of the prostate: a case report.
AB  - BACKGROUND: The published literature on primary prostatic extragastrointestinal
      stromal tumor (EGIST) is limited to several isolated case reports. No long-term
      follow-up is currently available for these patients in order to determine if the
      biologic behavior of prostatic gastrointestinal stromal tumor is different from
      those occurring in other sites. CASE: A 40-year-old man presented with symptoms
      of benign prostate hyperplasia. Magnetic resonance imaging revealed a huge
      prostatic mass restricted to the organ's capsule. After a complete resection and
      histopathologic study of the specimen, primary high-risk EGIST of the prostate
      was confirmed. The patient underwent adjuvant chemotherapy with imatinib. He has
      been observed for 32 months and is in good condition with no recurrence or
      metastasis. CONCLUSION: Primary EGIST of the prostate is an extremely rare
      entity. It should be carefully distinguished from other spindle cell lesions.
      Complete surgical resection and chemotherapy with imatinib are important
      strategies of treatment.

PMID- 24902374
TI  - Diabetes: the past, the present, and the challenging future.

PMID- 24902375
TI  - HbA1c for the diagnosis of diabetes.

PMID- 24902376
TI  - An integrated framework for clinical research: complementing sequencing with high
      resolution CNV detection.

PMID- 24902377
TI  - Biomarker research: its coming impact on the clinical lab.

PMID- 24902378
TI  - Pre-analytical errors: their impact and how to minimize them.

PMID- 24902379
TI  - Flow cytometry: principles and practices.

PMID- 24902380
TI  - Integrated community-based diagnostics services: a critical success factor in
      value-based reimbursement.

PMID- 24902381
TI  - Understanding the CLIA individualized quality control plan (IQCP).

PMID- 24902383
TI  - Going forward, pathologists and laboratories are no longer EHR donors.

PMID- 24902382
TI  - Choosing wisely: selecting the right test for the right patient at the right
      time.

PMID- 24902384
TI  - Alternate (non-array) SNP detection methods.

PMID- 24902386
TI  - Inaugural speech of the 152nd President.

PMID- 24902387
TI  - Emerging infectious diseases as public health threats.

PMID- 24902388
TI  - HIV/AIDS: a personal retrospective on a prototypical pandemic.
AB  - The HIV/AIDS pandemic richly illustrates the historian Charles Rosenberg's
      construct of epidemics as four-act plays: progressive revelation, the management
      of randomness, the negotiation of a public response, and subsidence and
      retrospection. In developed countries, we are now in Act Four. Among the numerous
      areas of HIV/AIDS that invite reflection, I've focused on its implications for
      medicine as a profession as opposed to a job or trade. The availability of
      effective technology determines the relative importance of competence (doing the
      right thing well; basic professionalism) and "compassion" (service that clearly
      transcends self-interest; higher professionalism). Those of us who became "AIDS
      doctors" during the pandemic's early years were privileged to live through what
      amounted to a truncated history of medicine. It was quite a ride. But most of
      all, I remember patients, both individually and collectively, from those early
      years. My proudest achievement is that none of my private patients died in a
      hospital. My most-cherished memento is a paperback book bequeathed to me by the
      widow of "Jake"-the early AIDS victim who never told his wife how he got those
      scars on his forearms. She'd inscribed it: "Dear Dr. Bryan, Thank you for letting
      me die gracefully." She and many others gave me lessons in courage and in what it
      means to be a doctor.

PMID- 24902389
TI  - Unde venis? Amebiasis presenting as appendicitis.
AB  - A returning traveler presenting with fever accompanied by abdominal "pressure"
      and pain proved to have amebic appendicitis, amebic liver abscess, and probable
      recent amebic dysentery--a rare combination of findings amply illustrating the
      value of asking "Unde venis--from where do you come?"

PMID- 24902390
TI  - Emerging zoonotic and vector-borne diseases pose challenges for the 21st century.

PMID- 24902391
TI  - Human rabies in South Carolina: case report, clinical issues, and public health
      perspectives.

PMID- 24902392
TI  - Antibiotic resistance: a clinical danger beyond 2013.

PMID- 24902393
TI  - Tuberculosis in South Carolina: old bugs learn new tricks.

PMID- 24902394
TI  - Clostridium difficile: case report and concise review of fecal microbiota
      transplantation.

PMID- 24902395
TI  - A blueprint for saving lives following disaster: consensus results of South
      Carolina's 2012 health security leaders conference.

PMID- 24902396
TI  - Inaugural speech.

PMID- 24902397
TI  - Effect of dentin conditioning on bond strength of fiber posts and dentin
      morphology: a review.
AB  - PURPOSE: Post and core systems are commonly used to restore endodontically
      treated teeth. A durable bond between fiber posts and dentin contributes to the
      success of the restorative treatment. Different irrigants are used during post
      space preparation and various studies have investigated the effects of these
      chemical agents on bond strength and dentin morphology. METHODS: The MEDLINE
      PubMed, Cochrane, and SCOPUS databases were searched for appropriate papers
      addressing the effects of irrigants on bonding of fiber posts to dentin and on
      dentin morphology. Databases were searched from 2002 through 2012. The search was
      performed using a variety of keywords including fiber posts, bond strength, post
      space preparation, post space irrigation, and smear layer removal. RESULTS: Using
      multiple key words and different strategies, 68 publications were initially
      screened. The abstracts of these 68 publications were scanned for relevance, and
      50 full-text articles were selected and read in detail. Thirty publications which
      discussed the effect of various intracanal irrigants on bond strengths of fiber
      posts and dentin morphology were incorporated in this review. Following review of
      all relevant papers, it can be concluded that bond strengths of fiber posts to
      radicular dentin can be affected by the irrigants used and that various irrigants
      affect different types of resin cements differently.

PMID- 24902398
TI  - Immediate post-application effect of professional prophylaxis with 8% arginine
      calcium carbonate desensitizing paste on hypersensitive teeth. A practitioner
      based clinical trial.
AB  - PURPOSE: This practitioner-based clinical trial compared the pain reduction
      achieved by professional prophylaxis with 8% arginine calcium carbonate (CaCO3)
      desensitizing paste versus 5% potassium nitrate (KNO3) toothpaste on adult
      patients with tooth hypersensitivity. METHODS: All dentists in Hong Kong were
      invited to join the study. Each participating dentist identified six adult
      patients with hypersensitive teeth after scaling in the clinic. For each patient,
      the most hypersensitive tooth was selected. Each hypersensitive tooth was
      isolated and tested with a blast of compressed cold air delivered from a three-in
      one syringe. The patient was then asked to indicate a sensitivity score (SS) from
      0 to 10. Three patients received professional prophylaxis with 8% arginine CaCO3
      desensitizing paste (Group 1), and the other three received prophylaxis with
      desensitizing toothpaste containing 5% KNO3 and 1,450 ppm fluoride (Group 2). The
      teeth were tested for a second time with compressed cold air, and the patients
      were asked to report the SS again. A non-parametric test was used to analyze the
      results following a normality test of the SS. RESULTS: A total of 303 patients
      were recruited by 65 participating dentists. The mean age of the patients was
      40.1, and 59% were female. The median pre-treatment SS of Groups 1 and 2 were
      both 7, whereas the post-treatment SS were 3 and 4, respectively (P < 0.001). The
      median percentage reductions in sensitivity scores of Groups 1 and 2 were 57.14%
      and 38.75%, respectively (P < 0.001).

PMID- 24902399
TI  - MicroCT-based comparison between fluorescence-aided caries excavation and
      conventional excavation.
AB  - PURPOSE: To evaluate and compare the use of micro-computed tomography (microCT)
      to investigate the mineral concentration of the treated dentin surface after
      caries removal with fluorescence-aided caries excavation (FACE) and conventional
      excavation. METHODS: 20 extracted human teeth with dentin caries were bisected
      through the lesion center into two halves which were distributed to a FACE and a
      conventional excavation group. Tungsten-carbide round burs were used for both
      groups. Each specimen was investigated with microCT after excavation. The
      obtained images of all the specimens were evaluated using Image J. Based on the
      grey values, the linear attenuation coefficients were calculated. Four resin
      embedded solid hydroxyapatite phantoms with the gradually increased mineral
      concentration were used to obtain a calibration curve and equation. Finally, the
      mineral concentration values of the superficial dentin of each specimen after
      removal and sound dentin were calculated. The data were compared with the
      Student's t-test. RESULTS: The statistical results showed that the linear
      attenuation coefficient (LAC) of the treated surface was significantly lower (P <
      0.0001) in the FACE group with a mean value of 2.13 +/- 0.33 cm9-1). The value of
      the conventional excavation group was 2.98 +/- 0.19 cm(-1). The LAC of sound
      dentin was 3.89 +/- 0.10 cm(-1). By using the calibration equation, the
      calculated mineral concentration of the superficial dentin after caries removal
      were 0.68 +/- 0.14 g/cm3 in the FACE group and 1.05 +/- 0.08 g/cm3 in the
      conventional excavation group. The mineral concentration of sound dentin was 1.44
      +/- 0.04 g/cm3. The mineral concentration of the superficial dentin after caries
      removal in the FACE group was about 47% of that of sound dentin, while the value
      in the conventional excavation group was approximately 73% of that of sound
      dentin. Under the conditions of this in vitro study, the results of the microCT
      evaluation may imply that FACE was more conservative than conventional
      excavation.

PMID- 24902400
TI  - Flexural resistance of Cerec CAD/CAM system ceramic blocks. Part 2: Outsourcing
      materials.
AB  - PURPOSE: To test different Cerec CAD/CAM system ceramic blocks, comparing mean
      flexural strength (sigma), Weibull modulus (m), and Weibull characteristic
      strength (sigma0) in an ISO standardized set-up. METHODS: Following the recent
      ISO Standard (ISO 6872:2008), 11 types of ceramic blocks were tested: IPS e.max
      CAD MO, IPS e.max CAD LT and IPS e.max CAD HT (lithium disilicate glass-ceramic);
      In-Ceram SPINELL, In-Ceram Alumina and In-Ceram Zirconia (glass-infiltrated
      materials); inCoris AL and In-Ceram AL (densely sintered alumina); In-Ceram YZ,
      IPS e.max Zir-CAD and inCoris ZI (densely sintered zirconia). Specimens were cut
      out from ceramic blocks, finished, crystallized/infiltrated/sintered, polished,
      and tested in a three-point bending test apparatus. Flexural strength, Weibull
      characteristic strength, and Weibull modulus were obtained. RESULTS: A
      statistically significant difference was found (P < 0.001) among lithium
      disilicate glass-ceramic (sigma = 272.6 +/- 376.8 MPa, m = 6.2 +/- 11.3, sigma0 =
      294.0 +/- 394.1 MPa) and densely sintered alumina (sigma = 441.8 +/- 541.6 MPa, m
      = 11.9 +/- 19.0, sigma0 = 454.2 +/- 565.2 MPa). No statistically significant
      difference was found (P = 0.254) in glass infiltrated materials (sigma = 376.9 +/
      405.5 MPa, m = 7.5 +/- 11.5, sigma0 = 393.7 +/- 427.0 MPa). No statistically
      significant difference was found (P = 0.160) in densely sintered zirconia (sigma
      = 1,060.8 +/- 1,227.8 MPa, m = 5.8 +/- 7.4, sigma0 = 1,002.4 +/- 1,171.0 MPa).
      Not all the materials tested fulfilled the requirements for the clinical
      indications recommended by the manufacturer.

PMID- 24902401
TI  - Role of fluoridated dentifrices in root caries formation in vitro.
AB  - PURPOSE: To evaluate in vitro root caries formation in human permanent teeth and
      to determine the effects of commercially available dentifrices containing
      different amounts of fluoride, while employing a well-tested artificial caries
      system using an acidified gel. METHODS: Root surfaces from caries-free human
      permanent teeth (n = 10) underwent debridement and fluoride-free prophylaxis. The
      tooth roots were sectioned into six portions, and acid-resistant varnish was
      placed with two sound root surface windows exposed on each tooth portion. Each
      portion from a single tooth was assigned to a treatment group: (1) No treatment
      control; (2) Denticious 5000 dentifrice (5,000 ppm F + xylitol); (3) PreviDent
      5000 (5,000 ppm F); (4) AIM dentifrice (1,500 ppm F); (5) Listerine dentifrice
      (1,300 ppm F); and (6) Crest Regular Paste (1,500 ppm F). Tooth portions were
      treated with fresh dentifrice twice daily for 180 seconds, followed by fresh
      synthetic saliva rinsing over a 7-day period. Controls were exposed twice daily
      to fresh synthetic saliva rinsing over a 7-day period. In vitro root caries were
      created using an acidified gel (pH 4.25, 21 days). Longitudinal sections (three
      sections/tooth portion, 30 sections/group; 60 lesions/group) were evaluated for
      mean lesion depths (water imbibition, polarized light). Statistical analyses were
      performed using ANOVA and Duncan's Multiple Range test. RESULTS: Mean lesion
      depths were 389 +/- 43 microm for No treatment - control, 223 +/- 33 microm for
      Denticious 5000 dentifrice, 242 +/- 42 microm for Prevident 5000, 337 +/- 29
      microm for AIM dentifrice, 297 +/- 37 microm for Listerine dentifrice, and 282 +/
      34 microm for Crest Regular Paste dentifrice. All treatment groups had mean
      depths significantly less than the No treatment - control group (P < 0.05).
      Denticious 5000 and PreviDent 5000 had significantly reduced mean depth compared
      with the other dentifrice treatment groups (P < 0.05).

PMID- 24902402
TI  - Effect of simulated intraoral erosion and/or abrasion effects on etch-and-rinse
      bonding to enamel.
AB  - PURPOSE: To assess the influence of simulated oral erosive/abrasive challenges on
      the bond strength of an etch-and-rinse two-step bonding system to enamel using an
      in situ/ex vivo protocol. METHODS: Bovine enamel blocks were prepared and
      randomly assigned to four groups: CONT - control (no challenge), ABR - 3x/day-1
      minute toothbrushing; ERO - 3x/day - 5 minutes extraoral immersion into regular
      Coca Cola; and ERO+ABR - erosive protocol followed by a 1-minute toothbrushing.
      Eight blocks were placed into an acrylic palatal appliance for each volunteer (n
      = 13), who wore the appliance for 5 days. Two blocks were subjected to each of
      the four challenges. Subsequently, all the blocks were washed with tap water and
      Adper Single Bond 2/Filtek Z350 were placed. After 24 hours, 1 mm2 beams were
      obtained from each block to be tested with the microtensile bond strength test
      (50 N load at 0.5 mm/minute). The data were statistically analyzed by one-way RM
      ANOVA and Tukey's tests (alpha = 0.05). RESULTS: No difference was detected among
      the ABR, ERO, and CONT groups (P > 0.05). ERO+ABR group yielded lower bond
      strengths than either the ABR and ERO groups (P < 0.0113).

PMID- 24902403
TI  - In vitro detection of DNA damage in human leukocytes induced by combined effect
      of resin composites and adhesive systems.
AB  - PURPOSE: To simultaneously evaluate the genotoxicity of dental composites and
      adhesive systems in vitro using a cytogenetic assay, with respect to the
      influence of composite shade. METHODS: Genotoxicity assessment was carried out in
      human peripheral blood leukocytes using the comet assay. Three resin composite
      materials, two microhybrids and one nano-hybrid, in shade A1 and A3.5 were used
      with manufacturer-recommended four adhesive systems. Cultures were treated for 48
      hours with samples after elusion for 1 hour, 1 day, 7 days or 30 days, in two
      different concentrations (4.16 mg/mL, 8.33 mg/mL). Kruskall-Wallis test was used
      for the statistical analysis (alpha = 0.05). RESULTS: For combinations of micro
      hybrid composite (A3.5) with two self-etch adhesives (16.1 +/- 5.50 and 16.2 +/-
      9.52) after exposure to samples eluted for 1 day, the incidence of primary DNA
      damage was significantly higher than for the corresponding negative control (14.7
      +/- 2.85). Genotoxicity was also higher after treatment with samples eluted for 1
      hour (15.3 +/- 4.70) and 1 day (15.3 +/- 9.10), comprised of nano-hybrid
      composite (A1) with self-etch adhesive in relation to the control (13.1 +/-
      1.70). There was no clear trend of increased DNA damage in material combinations
      with darker shades of composites. Material composition and higher material
      concentrations showed greater influence on the genotoxicity.

PMID- 24902404
TI  - Laboratory evaluation of the effect of toothbrushing on surface gloss of resin
      composites.
AB  - PURPOSE: To determine changes in surface gloss of different composite materials
      after laboratory toothbrushing simulation. METHODS: 40 specimens were fabricated
      for each material (Filtek Supreme XTE, Renamel, Empress Direct, Gradia Direct,
      Edelweiss, G-aenial, Venus Pearl and Venus Diamond) and polished with 120-, 220-,
      500-, 1200-, 2400- and 4000- grit SiC abrasive paper, respectively. Gloss
      measurements were made with a glossmeter prior to testing procedures and then
      subjected to simulated toothbrushing for 5, 15, 30 and 60 minutes by means of an
      electrical toothbrush with a pressure of 2N while being immersed in a 50 RDA
      toothpaste slurry. Four samples per group were analyzed under SEM immediately
      after polishing procedures and four samples after 60 minutes simulated
      toothbrushing in order to evaluate the causes of the gloss decrease. Human enamel
      was the control group. Statistical analysis was performed using Kruskal Wallis
      and Tukey's post-hoc test (P < 0.05). RESULTS: Resin composite initial gloss
      values ranged from 78.2 to 100.5 at baseline to 13.8 to 62.4 after 1 hour of
      brushing. Highest gloss values were obtained by Filtek Supreme XTE and Renamel (P
      < 0.05), followed by Empress Direct. Lowest values were obtained with Venus
      Diamond, Venus Pearl, G-aenial and Edelweiss. Human enamel was the only material
      which maintained its gloss throughout the brushing procedure (110.4 after 60
      minutes). SEM analysis revealed different patterns of surface degradation
      dependant on the material.

PMID- 24902405
TI  - Efficacy of hydrogen-peroxide-based mouthwash in altering enamel color.
AB  - PURPOSE: To analyze the efficacy of Colgate Plax Whitening mouthwash containing
      1.5% hydrogen peroxide. METHODS: 30 enamel fragments, obtained from the proximal
      surfaces of human third molars were darkened with Orange II methyl orange. The
      fragments were divided into three groups according to the type of bleaching agent
      applied (n = 10): (1) 10% carbamide peroxide gel (positive control, PC) was
      applied for 2 hours/day for 28 days; (2) a solution containing 1.5% hydrogen
      peroxide (Plax) was applied for 4 minutes once a day for 28 days, and (3) no
      bleaching agent, kept in artificial saliva (negative control, AS). The specimens
      were kept in artificial saliva between treatment intervals. The specimens were
      photographed before darkening (baseline), after darkening and before lightening
      and on the 28th day of whitening. Afterwards, they were analyzed with color
      measurement software using the CIELab system. The data for the L*, a* and b*
      parameters were submitted to two-way ANOVA with repeated measures. The values of
      deltaL *, deltaa *, deltab * and deltaE* were calculated using two procedures:
      (1) darkened versus original, and (2) bleached versus darkened. This data was
      submitted to the one-way ANOVA test. Multiple comparisons were conducted using
      the Tukey test (alpha = 0.05). RESULTS: When the specimens were subjected to
      bleaching agents, there was a significant increase in the brightness (L*
      parameter) of the enamel exposed to the gel and also to the bleaching solution.
      However, higher brightness was observed for the PC (gel) group. As for the axis
      a* parameters, there were no significant differences between the bleaching
      products. Regarding the axis b* parameters, the PC group underwent major changes
      (indicating a color change toward blue chroma), statistically greater than those
      of the Plax group. After bleaching, there was a significantly greater color
      change (deltaE*) in the PC group. Although the Plax solution caused a color
      change, it was less than that produced by the gel. The slightest color change was
      observed in the control group, in which no bleach was used. The mouthwash
      containing hydrogen peroxide was able to lighten the darkened human enamel, but
      to a lesser degree than the lightening produced by 10% carbamide peroxide.

PMID- 24902406
TI  - Resistance against bacterial leakage of four luting agents used for cementation
      of complete cast crowns.
AB  - PURPOSE: To assess the sealing properties of four luting materials used for
      cementation of full cast crowns. METHODS: 40 human premolars were prepared with a
      chamfer finish line. Stone dies were fabricated and copings were waxed, invested
      and cast in gold. Ten samples (n = 10) were randomly assigned to four groups. In
      two groups, resin modified glass-ionomer cements were used, ACTIVA BioACTIVE
      CEMENT/BASE/LINER and FujiCem2; the third group received the self-adhesive resin
      cement Embrace WetBond, while the fourth group served as control with a zinc
      phosphate cement. After cementation, excess cement was removed followed by bench
      set for 10 minutes. All samples were stored in water at 37 degrees C and
      subjected to thermal cycling (x2000 between 5 and 55 degrees C). Subsequently the
      occlusal surface was reduced exposing the dentin. After sterilization the
      specimens were subjected to bacterial microleakage with E. faecalis in a dual
      chamber apparatus for a period of 60 days. Bacterial leakage was checked daily.
      Data were analyzed using the Kaplan-Meyer survival test. Significant pairwise
      differences were analyzed using the Log Rank test and the Fishers' exact test at
      P < 0.05. RESULTS: ACTIVA BioACTIVE-CEMENT/BASE/LINER, FujiCem2 and Embrace
      WetBond showed the lowest microleakage scores and differed statistically
      significantly (P < 0.05) from zinc phosphate cement.

PMID- 24902407
TI  - A 4-week clinical comparison of an oscillating-rotating power brush versus a
      marketed sonic brush in reducing dental plaque.
AB  - PURPOSE: To assess the plaque removal efficacy of an oscillating-rotating power
      brush relative to a newly-introduced sonic power brush. METHODS: This study used
      a randomized, examiner-blind, single-center, two-treatment, parallel group 4-week
      design. Subjects with pre-existing plaque scores of at least 1.75 on the Turesky
      Modification of the Quigley-Hein Plaque Index (TMQHPI) were evaluated for
      baseline whole mouth and approximal plaque scores. They received either the
      oscillating-rotating brush (Oral-B Professional Care 1000, sold as Oral-B
      Professional Care 600 in some regions, with the Oral-B Precision Clean brush
      head, D16u/EB20) or the sonic brush (Colgate ProClinical C200 with Colgate Triple
      Clean brush head) and brushed twice-daily with the assigned brush and a standard
      fluoride dentifrice for 4 weeks before returning for plaque measurements. Prior
      to baseline and the Week 4 measurements, participants abstained from oral hygiene
      for 12 hours and from eating, chewing gum and drinking for 4 hours. RESULTS: A
      total of 131 subjects were enrolled in the study at baseline, with all completing
      the study: 65 in the oscillating-rotating group, and 66 in the sonic group. Both
      brushes significantly reduced plaque over the 4-week study period. The
      oscillating-rotating brush was statistically significantly more effective in
      reducing plaque (P < 0.001) than the sonic brush. Compared to the sonic power
      brush, the adjusted mean plaque reduction scores for the oscillating-rotating
      power brush were more than five times greater for whole mouth and approximal
      areas.

PMID- 24902408
TI  - Assessment of apical periodontitis in dogs and humans: a review.
AB  - Veterinary dentists commonly encounter apical periodontitis in dogs. An overview
      of the disease is presented, concentrating on pathogenesis and mechanisms of
      healing. Assessment modalities are reviewed and interpretations of treatment
      success and failure are discussed. The limitations of readily available
      diagnostic equipment are illustrated. The benefits of identifying the causative
      agent and resultant pathosis should not be overlooked. Well-designed clinical
      studies evaluating various methods of long-term follow-up for apical
      periodontitis in dogs are needed.

PMID- 24902409
TI  - Effect of preparation surface area on the clinical outcome of full veneer crowns
      in dogs.
AB  - Crown therapy is commonly used in veterinary medicine to provide support to teeth
      which have previously fractured, received root canal therapy, have significant
      wear, or experienced other detrimental removal of tooth substance. As with
      several aspects of veterinary medicine, many of the recommendations or guidelines
      for crown therapy originate from human dentistry, which are then transferred to
      veterinary patients. Due to the significant difference in the anatomy of teeth
      and function of the oral cavity between humans and dogs, these guidelines need to
      be studied to determine the appropriateness of their use in veterinary patients.
      This article evaluates the relationship between surface area of the preparation
      and clinical outcome of full veneer crown therapy of the canine tooth in dogs.
      Although there appeared to be a positive relationship between preparations with
      greater surface area and successful clinical outcome, it was not found to be
      statistically significant.

PMID- 24902410
TI  - Dental wax decreases calculus accumulation in small dogs.
AB  - A dental wax was evaluated after unilateral application in 20 client-owned, mixed
      and purebred small dogs using a clean, split-mouth study model. All dogs had
      clinical signs of periodontal disease including plaque, calculus, and/or
      gingivitis. The wax was randomly applied to the teeth of one side of the mouth
      daily for 30-days while the contralateral side received no treatment. Owner
      parameters evaluated included compliance and a subjective assessment of ease of
      wax application. Gingivitis, plaque and calculus accumulation were scored at the
      end of the study period. Owners considered the wax easy to apply in all dogs.
      Compliance with no missed application days was achieved in 8 dogs. The number of
      missed application days had no effect on wax efficacy. There was no significant
      difference in gingivitis or plaque accumulation scores when comparing treated and
      untreated sides. Calculus accumulation scores were significantly less (22.1 %)
      for teeth receiving the dental wax.

PMID- 24902411
TI  - Endodontic therapy of a mandibular canine tooth with irreversible pulpitis
      secondary to dentigerous cyst.
AB  - Dentigerous cysts are uncommon, yet are being reported with increasing frequency
      in the veterinary literature. Dentigerous cysts are a type of benign odontogenic
      cyst associated with impacted teeth, most commonly the mandibular first premolar
      tooth. Significant bone destruction can occur secondary to the expansion of a
      dentigerous cyst. The expanding cyst can lead to pathology of neighboring teeth,
      which can include external root resorption or pulpitis. Intraoral dental
      radiographs are imperative to properly assess the presence and extent of a
      dentigerous cyst, as well as the status of the neighboring teeth. This case
      report describes treatment for dentigerous cyst including cyst lining curettage,
      mandibular bone regeneration, and endodontic therapy for a canine tooth with
      irreversible pulpitis.

PMID- 24902412
TI  - Parotid salivary duct stenosis following caudal maxillectomy.
AB  - Parotid salivary duct dilation was diagnosed in a 9-year-old male dog. The dog
      had undergone caudal maxillectomy on the ipsilateral side 2-years prior to
      presentation. Treatment consisted of parotid salivary duct excision and
      superficial parotidectomy that lead to the resolution of clinical signs.
      Transient facial neuropraxia was observed immediately after surgery and resolved
      spontaneously after 2-weeks. Parotid salivary duct dilation should be considered
      as a chronic postoperative complication following caudal maxillectomy.

PMID- 24902413
TI  - Sharpening periodontal instruments.

PMID- 24902415
TI  - They make it so easy....

PMID- 24902414
TI  - Class I restoration of maxillary first molar caries in a dog.

PMID- 24902416
TI  - Why I'm not using an EMR...

PMID- 24902417
TI  - Outgoing president's page 2013-2014. Lessons learned and reaffirmed.

PMID- 24902418
TI  - Incoming president's page 2014-25. 49th.... Why not try for 50th?!

PMID- 24902419
TI  - Compounded estradiol cream: a cost conscious alternative.
AB  - BACKGROUND: Vaginal estrogen is a common therapy for many gynecologic conditions.
      Medication cost poses a barrier to medication compliance. The purpose of our
      study is to report patient cost savings by utilizing compounding pharmacies in
      the preparation of topical vaginal estrogen. METHODS: A survey of 10 topical
      vaginal estrogen compounding pharmacies was performed and prescription cost data
      was obtained. The University of Oklahoma Outpatient Pharmacy and the 2008 Wolters
      Kluwer Health Pharmaceutical Audit Suite were cost comparisons for compounded
      estrogen. All data was processed using statistical software yielding descriptive
      statistics. RESULTS: The average cost of compounded estrogen was $42.22. At the
      University of Oklahoma Outpatient Pharmacy, average cost for branded vaginal
      estrogen preparation was $137.70. The national cost average for branded vaginal
      estrogen preparations was $82.42. Cost savings of $94.98 (69%) locally and $40.20
      (51%) nationally was identified. CONCLUSIONS: Compounded estrogen is a cost
      conscious alternative than branded preparations.

PMID- 24902420
TI  - A comparison of Tier 1 and Tier 3 medical homes under Oklahoma Medicaid program.
AB  - INTRODUCTION: The patient-centered medical home (PCMH) is a team-based model of
      care that seeks to improve quality of care and control costs. The Oklahoma Health
      Care Authority (OHCA) directs Oklahoma's Medicaid program and contracts with 861
      medical home practices across the state in one of three tiers of operational
      capacity: Tier 1 (Basic), Tier 2 (Advanced) and Tier 3 (Optimal). Only 13.5% (n =
      116) homes are at the optimal level; the majority (59%, n = 508) at the basic
      level. In this study, we sought to determine the barriers that prevented Tier 1
      homes from advancing to Tier 3 level and the incentives that would motivate
      providers to advance from Tier 1 to 3. Our hypotheses were that Tier 1 medical
      homes were located in smaller practices with limited resources and the providers
      are not convinced that the expense of advancing from Tier 1 status to Tier 3
      status was worth the added value. METHODS: We analyzed OHCA records to compare
      the 508 Tier 1 (entry-level) with 116 Tier 3 (optimal) medical homes for
      demographic differences with regards to location: urban or rural, duration as
      medical home, percentage of contracts that were group contracts, number of
      providers per group contract, panel age range, panel size, and member-provider
      ratio. We surveyed all 508 Tier 1 homes with a mail-in survey, and with focused
      follow up visits to identify the barriers to, and incentives for, upgrading from
      Tier 1 to Tier 2 or 3. RESULTS: We found that Tier 1 homes were more likely to be
      in rural areas, run by solo practitioners, serve exclusively adult panels, have
      smaller panel sizes, and have higher member-to-provider ratios in comparison with
      Tier 3 homes. Our survey had a 35% response rate. Results showed that the most
      difficult changes for Tier 1 homes to implement were providing 4 hours of after
      hours care and a dedicated program for mental illness and substance abuse. The
      results also showed that the most compelling incentives for encouraging Tier 1
      homes to upgrade their tier status were less"red tape"with prior authorizations,
      higher pay, and help with panel member follow-up. DISCUSSION: Multiple
      interventions may help medical homes in Oklahoma advance from the basic to the
      optimal level such as sharing of resources among nearby practices, expansion of
      OHCA online resources to help with preauthorizations and patient follow up, and
      the generation and transmission of data on the benefits of medical homes.

PMID- 24902421
TI  - Total patient care is a collaborative effort.

PMID- 24902422
TI  - Canadian oncology nursing journal.

PMID- 24902423
TI  - Role of oncology nurses in integrated knowledge translation.

PMID- 24902424
TI  - Central line practice in Canadian blood and marrow transplant.
AB  - More than 800 blood cell and bone marrow transplants are performed annually in
      Canada to treat fatal cancers and rare blood disorders. Central vascular access
      is fundamental in blood and marrow transplant nursing to facilitate chemotherapy
      and blood product infusions. A tunnelled Central Venous Catheter (CVC) is the
      vascular access device-of-choice in the cell and marrow transplant population.
      Several practice guidelines direct nursing policy and procedure for CVC
      management and care. CVC insertion and removal guidelines are increasingly
      relevant given the widening scope of advanced practice nursing. Unresolved issues
      are noted among the most heavily cited CVC practice recommendations accessible
      via the Centers for Disease Control and Prevention (CDC). A descriptive survey
      based on the CDC guidelines was conducted to identify potential variability in
      CVC strategies in Canadian blood and marrow transplant nursing. Survey results
      indicate nationwide differences in catheter site selection, educational
      strategies, dressing strategies, delegation of dressing changes, and volumes of
      flushing and locking solutions used to manage catheter patency. Variability in
      practice coincides with gaps in the evidence identified in practice
      recommendations. Future studies comparing specific care approaches to device
      associated complications are needed to resolve issues and strengthen practice
      guidelines.

PMID- 24902425
TI  - Remote symptom support training programs for oncology nurses in Canada: an
      environmental scan.
AB  - The overall aim of this study was to explore current remote symptom support
      training programs provided to nurses in ambulatory oncology programs across
      Canada, using a survey-methods environmental scan. Of 36 delivered invitations,
      28 programs responded (77.8%) representing 10 provinces. Of 25 programs that
      offer telephone symptom support, 17 provide symptom support training, seven do
      not, and one did not say. Seven programs shared training materials with the
      investigators and elements of training included: symptom management guidelines (n
      = 6), telephone triage process/principles (n = 5), competent telephone practices
      (n = 4), documentation (n = 4), professional standards (n = 3), role-play (n =
      3), communication skills/etiquette (n = 3), and monitoring quality (n = 1).
      Formats included: presentations (n = 3), paper-based resources (n = 3), or e
      learning modules (n = 1). No training programs were rigorously evaluated.
      Training in telephone nursing symptom support across oncology programs is
      variable. Opportunities exist to identify core competencies and evaluate if
      training programs enhance delivery of remote cancer symptom support.

PMID- 24902426
TI  - Chemotherapy at home: keeping patients in their "natural habitat".
AB  - Escalating cancer rates and an increase in the complexity and duration of
      chemotherapy regimens have brought the issue of cancer treatment at home to the
      forefront. For the participants of this study, home chemotherapy was offered as a
      potential treatment choice. Ten patients who accepted home chemotherapy were
      interviewed using the methodology of interpretive description. They shared their
      experiences of receiving chemotherapy at home, and identified home as being a
      "natural habitat" in which they were better able to adapt to their circumstances.
      Patients were able to redistribute their resources including time, energy, and
      finances in ways that were meaningful to them. They felt the care provided was
      enhanced and they were more receptive to teaching. Lastly, participants viewed
      themselves as being less ill and better able to cope with their treatments. Given
      the results of this study and other research available, chemotherapy at home
      should be considered an option for patients with cancer.

PMID- 24902427
TI  - Survey about the use of scalp cooling to prevent alopecia during breast cancer
      chemotherapy treatment in Canada.
AB  - Alopecia is a side effect of chemotherapies used in breast cancer. Scalp cooling
      is a technique preventing alopecia, but its use remains controversial. We
      conducted a survey about knowledge of scalp cooling and interest in conducting a
      randomized clinical trial (RCT). An invitation was sent to 1,022 participants and
      a total of 139 individuals responded to the survey. The majority knew about the
      existence of scalp cooling. Ninety per cent thought that an RCT was needed and
      would participate. The survey revealed different potential problems associated
      with the increased chair time, limited space, and safety. We concluded that an
      RCT is needed and that the trial must include evaluation on the impact on health
      care system resources and safety.

PMID- 24902428
TI  - Cancer nursing in low-middle income countries.

PMID- 24902429
TI  - Making a decision about your project: is it quality improvement or research?

PMID- 24902431
TI  - Committed to competence. Feedback about FEEDBACK.

PMID- 24902430
TI  - Healthy aging in Alberta.

PMID- 24902432
TI  - Policy and practice consultation evaluation 2013.

PMID- 24902433
TI  - 2012-2013 summary of CARNA practice consultations.

PMID- 24902434
TI  - Revised medication guidelines.

PMID- 24902435
TI  - Medication reconciliation: working together in Albert.

PMID- 24902436
TI  - Be part of the solution.

PMID- 24902437
TI  - Canadian nurses protective society infoLAW: legal status of an apology.

PMID- 24902438
TI  - The baby friendly initiative.

PMID- 24902439
TI  - Pediatric obesity: what can registered nurses do.

PMID- 24902440
TI  - RN optimizes EMR effectiveness at the Alex.

PMID- 24902441
TI  - The merits of engagement.

PMID- 24902442
TI  - Advancing holistic nursing & transforming health care: showing up, stepping in,
      reaching out.

PMID- 24902443
TI  - Intentionality: the matrix of healing creates caring, healing presence.

PMID- 24902444
TI  - Code Lavender: Initiating holistic rapid response at the Cleveland Clinic.

PMID- 24902445
TI  - Transforming the patient experience through presence and intention.

PMID- 24902446
TI  - Allowing for miracles: the vulnerable choice of intentionality and presence.

PMID- 24902447
TI  - Holistic nursing research with homeless youths.

PMID- 24902448
TI  - Practice intentionality & presence with mantram repetition.

PMID- 24902449
TI  - Intentional self-discovery.

PMID- 24902450
TI  - The concept of reentry in the addicted anesthesia provider.
AB  - Substance abuse among healthcare providers is a serious issue affecting patient
      care and patient outcomes. Substance abuse among anesthesia providers is of
      extreme concern because of the type of drugs and easy access providers are
      granted. Impaired anesthesia providers jeopardize not only their own safety but
      also the safety of their patients. Accidental death of either the healthcare
      provider or the patient is often the unfortunate first sign of addiction among
      anesthesia providers. Most states, in the United States offer treatment programs
      for anesthesia providers as an option to disciplinary action, and on completion
      of the Substance abuse is the primary occupational program, the provider is
      allowed to reenter practice. Successful reentry is sometimes rare, and providers
      are plagued with the stigma of abuse, shame, and a high incidence of relapse.
      This article is an analysis of the concept of reentry into anesthesia practice,
      using Walker and Avant's model of concept analysis. Tenets of successful reentry
      are discussed. Implications for further concept analysis, practice, and research
      are presented.

PMID- 24902451
TI  - An update: use of laryngeal mask airway devices in patients in the prone
      position.
AB  - Some providers advocate using laryngeal mask airways (LMAs) for procedures
      performed in the prone position to meet the demands of quicker operating room
      turnover time requirements, staffing reductions and the desire to expedite
      patient recovery in the postoperative period. We provide an update to a 2010
      systemic review examining the use of LMAs in patients in the prone position. Six
      peer-reviewed articles described the use of LMAs in prone patients: a randomized
      controlled trial, 2 description studies, a case series, and 2 case reports. The
      risk of publication bias was possibly high. This evidence, mostly from lower
      level sources, supports the use of the LMA in this setting, with risks comparable
      to when LMAs are used in patients in the supine position. Experienced providers
      should carefully select patients and procedures when considering using LMAs for
      patients in the prone position. There must be a plan to control the airway if
      problems are encountered with the LMA. These devices might be considered as a
      bridge device when a prone patient is accidentally extubated. Additional rigorous
      studies are needed before use of LMAs in this manner can be widely recommended.

PMID- 24902452
TI  - Anesthetic management of Costello syndrome: a case report.
AB  - Costello syndrome is a rare genetic disorder with an estimated 300 medical cases
      worldwide. Typical features that characterize this syndrome include short
      stature, macrocephaly, developmental delay, loose skin folds, distinctive coarse
      facial features, and multiorgan system anomalies. The following case report
      discusses the anesthetic management for a 3-year-old boy undergoing general
      anesthesia for a scheduled dental restoration, hydrocelectomy, inguinal hernia
      repair, and bilateral myringotomy with placement of pressure equalization tubes.
      A scarcity of literature for the anesthetic management of Costello syndrome (also
      known as faciocutaneoskeletal syndrome) exists. Utilizing an overview of the
      pertinent literature, clinical practice recommendations are suggested for the
      anesthetic implications of managing a pediatric patient with this rare syndrome.

PMID- 24902453
TI  - Ventilation with increased apparatus dead space vs positive end-expiratory
      pressure: effects on gas exchange and circulation during anesthesia in a
      randomized clinical study.
AB  - Atelectasis formation can be reduced by positive end-expiratory pressure (PEEP),
      but resulting increases in intrathoracic pressure could affect circulation. We
      have earlier demonstrated that increased tidal volumes with larger apparatus dead
      space improves oxygenation and sevoflurane uptake. In the present study, we
      hypothesize that isocapnic ventilation with increased tidal volumes increases
      oxygen and sevoflurane uptake similar to ventilation with PEEP, but with less
      impact on cardiac output. Thirty patients, with ASA physical status 1 or 2,
      scheduled for elective open colon surgery were randomly assigned to be ventilated
      with either PEEP at 10 cm H20 (PEEP, 15 patients) or increased tidal volumes
      achieved with larger apparatus dead space but with zero end-expiratory pressure
      (DS group, 15 patients). Oxygen tension and arterial sevoflurane concentration
      were significantly higher in the DS group (P < .05). Cardiac output decreased
      significantly less in the DS group compared with the PEEP group (5% and 33%,
      respectively; P < .05). Consequently, isocapnic ventilation with increased tidal
      volumes using apparatus dead space increased oxygen and sevoflurane tensions in
      arterial blood and preserved cardiac output better than did PEEP.

PMID- 24902454
TI  - Comparison of 3 ultrasound-guided brachial plexus block approaches for cubital
      tunnel release surgery in 120 ambulatory patients.
AB  - We wanted to determine whether 1 of 3 brachial plexus blocks was best for one of
      our most common surgeries, the cubital tunnel release with or without
      transposition of the ulnar nerve. Brachial plexus blocks can provide excellent
      results for upper extremity surgery, but we noticed inexplicable block failure
      for cubital tunnel releases with an incision in the proximal arm. In this case
      series, we initially reviewed 90 patients receiving axillary, infraclavicular, or
      supraclavicular blocks to determine if one block performed better for a surgical
      procedure that proceeds up the inner aspect of the arm. The theory that
      infraclavicular and supraclavicular blocks were superior for this surgery was not
      demonstrated in these patients. Success was not determined by the block chosen;
      however, the intercostobrachial nerve may be inconsistently blocked because it is
      difficult to visualize on ultrasound. We subsequently reviewed 30 more patients,
      but this time the volume of the intercostobrachial block was doubled. By
      increasing the volume, there appeared to be less need for surgeons to "touch up"
      blocks in the operating room. We suggest that increasing the volume of the
      intercostobrachial nerve block may improve success. Further studies to identify
      the intercostobrachial nerve by ultrasound are needed.

PMID- 24902455
TI  - Utility of thromboelastography during neuraxial blockade in the parturient with
      thrombocytopenia.
AB  - No consensus exists on when it is safe to administer neuraxial blockade in a
      patient with a low platelet count. It has been suggested that thromboelastography
      (TEG) may be useful in assessing platelet function in parturients with
      thrombocytopenia. The purpose of the study was to analyze the incidence of
      neurologic complications, if any, related to regional anesthesia in parturients
      with a platelet count less than 100,000 mm-3 and especially those with less than
      80,000 mm3 and normal TEG values. The data were prospectively collected during a
      3-year period. All parturients whose platelet count was less than 100,000 mm(-3)
      were required to have TEG before a neuraxial technique was administered. This
      case series suggests that neuraxial techniques in parturients can be performed
      with a platelet count greater than 56,000 mm3 and a normal TEG result.

PMID- 24902456
TI  - Evaluation of postprocedure cognitive function using 3 distinct standard sedation
      regimens for endoscopic procedures.
AB  - The primary purpose of this investigation was to evaluate postprocedure cognitive
      function associated with 3 distinct standard sedation regimens used for
      endoscopic procedures. A secondary aim was to identify complications requiring
      provider interventions. Subjects scheduled for colonoscopies were approached for
      enrollment the day of their procedure. A convenience sample of 96 subjects was
      randomly assigned. Cognitive function was recorded on the day of surgery using
      the Mini-Mental State Examination (MMSE) and 24 and 48 hours postoperatively
      using the Telephone Interview of Cognitive Status (TICS). The propofol plus
      fentanyl group had a mean TICS score of 34.53 at 24 hours compared with 34.96 at
      48 hours (P = .017). The midazolam plus fentanyl group had a mean TICS score of
      34.76 at 24 hours compared with 36.26 at 48 hours (P = .004). The propofol-alone
      group had a mean TICS score of 35.09 at 24 hours compared with 35.98 at 48 hours
      (P = .924). The results of this investigation indicate that the sedation regimen
      of propofol alone has the least impact on postprocedure cognitive function.
      Additionally, the number of jaw lift interventions was significantly higher in
      both groups who received fentanyl.

PMID- 24902457
TI  - Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a case
      report.
AB  - Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is a
      complex procedure used for the treatment of various types of cancer.
      Specifically, HIPEC has shown success where treatment failure sites (metastases)
      thrive. A classic example of one such area is the peritoneal surface, which
      remains a prominent failure site for patients with gynecologic and
      gastrointestinal cancer. Traditionally, most patients with advanced stages of
      cancer have undergone palliative procedures as part of their treatment modality
      or had no surgery at all. With the advent of cytoreductive surgery with HIPEC,
      patients with peritoneal cancer have shown increased survival rates. Anesthetic
      complications are common during this procedure with disturbances in hemodynamics,
      coagulation, and respiratory gas exchange. A knowledge of what to anticipate
      anesthetically will guide the practitioner to achieve successful management
      during and after the case. In this case report, a 71-year-old woman was treated
      for stage Ill peritoneal and ovarian cancer by cytoreductive surgery with HIPEC.

PMID- 24902458
TI  - Anesthesia case management for endovascular aortic aneurysm repair.
AB  - The incidence of angiopathology involving the aorta and microvasculature is
      expected to become more prevalent because of increased life expectancy and
      incidence of obesity. With the advent of endovascular aortic repair (EVAR),
      patients who were not considered surgical candidates for abdominal aortic
      aneurysmectomy because of their tenuous physical status can undergo corrective
      treatment and return to their activities of daily living. Because of the limited
      invasiveness of the procedure, it is unnecessary to cross-clamp the aorta, which
      minimizes hemodynamic variability and release of inflammatory mediators. As a
      result, the rate of myocardial ischemia, acute kidney injury, mesenteric
      ischemia, and blood loss is decreased. However, there are serious complications
      that can occur with EVAR, which include cerebral and myocardial ischemia, rapid
      massive hemorrhage, damage to access vessels, and endoleak. Presently, the most
      common anesthetic technique provided to patients undergoing EVAR is local
      anesthesia and monitored anesthetic care. A thorough understanding of the
      surgical procedure, perioperative process, and anesthetic considerations is vital
      to provide comprehensive care.

PMID- 24902459
TI  - 2014 WVSMA physician practice conference & annual business meeting.

PMID- 24902460
TI  - Clinicians pocket guide. West Virginia physicians making a difference.

PMID- 24902461
TI  - Direct primary care membership medicine.

PMID- 24902462
TI  - Ultrasound guided greater occipital nerve blocks for post-traumatic occipital
      neuralgia.
AB  - Chronic headaches can be debilitating for many patients. They often have a
      nebulous etiology, unpredictable course, and can be difficult to manage. We
      describe a post-traumatic headache that began after a motor vehicle collision.
      The patient sustained multiple injuries including a scalp laceration and
      bilateral occipital condyle fractures. Oral agents were unable to quell this
      patient's headaches. The diagnosis of occipital neuralgia was suspected based on
      history and presentation. Our patient received dramatic relief after ultrasound
      guided bilateral greater occipital nerve blocks.

PMID- 24902463
TI  - Improved growth and development in premature infants managed with nasal
      continuous positive airway pressure.
AB  - OBJECTIVE: Our goal was to assess the association between the use of nasal
      continuous positive airway pressure (NCPAP) vs. conventional ventilation (CV) in
      premature infants and its effects on: 1) growth in the NICU and at follow up
      visits 2) neurodevelopmental outcomes measured by Bayley Infant
      Neurodevelopmental Screener (BINS) 3) the incidence of retinopathy of prematurity
      (ROP) and chronic lung disease (CLD). METHODS: A retrospective chart review of
      two groups of NICU patients was conducted. The first group was from 1/1999
      12/2000 (n = 140) and was managed by CV. The second group (n = 168) was from
      1/2003-12/2004 and was managed primarily by NCPAP. Categorical variables were
      analyzed using Pearson Chi Square. Mean numerical values were analyzed with the
      student t-test. RESULTS: There was no statistical difference between the groups
      in regard to 15 demographic and interventional variables. There were significant
      differences between the two groups in CLD (p < 0.05) and ROP (p < 0.01), mean
      weight at one month (p < 0.05), 9-12 months (p < 0.01) and 15-18 months (p <
      0.01), length at 4-6 months (p < 0.05), 9-12 months (p < 0.05), 15-18 months (p <
      0.01), and 2 years (p = .05), and in BINS scores at 9-12 months (p < 0.01) and 15
      18 months (p < 0.01). CONCLUSIONS: Managing babies with NCPAP therapy when
      compared with CV, significantly increased the weight at one month which was
      sustained at the 9-12 month and 15-18 month visits, increased length at all
      follow up visits, increased BINS scores at the 9-12 month and 15-18 month visits,
      and decreased the incidence of ROP and CLD.

PMID- 24902466
TI  - Streptococcus bovis bacteremia as the initial presentation of carcinoma of the
      gallbladder.
AB  - There is a well known association between Streptococcus bovis infection and the
      presence of a coexisting colonic adenocarcinoma. Association of S. bovis with
      other malignancies has only been rarely reported. We report a 77-year-old male
      who presented with with Streptococcus bovis bacteremia in the setting of acute
      cholecystitis. Given the association of colon adenocarcinoma and Streptococcus
      bovis bacteremia, colonoscopy was performed prior to cholecystectomy to evaluate
      a possible coexisting colon neoplasm, which was negative. At cholecystectomy, the
      patient was found to have a carcinoma of the gallbladder, which was treated with
      radical cholecystectomy and periportal lymphadenectomy. This is the first case of
      Streptococcus bovis infection and coexisting gallbladder cancer to be reported,
      and highlights the need for maintenance of a high index of suspicion for
      malignancies other than colon cancer when patients present with Streptococcus
      bovis bacteremia.

PMID- 24902464
TI  - Predictors of self-reported adherence to mammography screening guidelines in West
      Virginia women visiting a stationary facility.
AB  - The objectives of this study are to describe the characteristics of women age 40
      years and above who utilize a stationary mammography facility and to determine
      the predictors of self-reported adherence to mammography screening guidelines.
      Data were analyzed using the expanded version of Andersen Behavioral Model of
      Healthcare Utilization. Of the 1,104 women included in the analysis, 1,019 women
      (92.3%) reported having had a mammogram in the past two years. In logistic
      regression after adjusting for all the variables, older age, having health
      insurance, not having delayed medical care due to transportation problem, being
      adherent to clinical breast exam (CBE), Pap test and other routine screenings and
      having positive views about mammography screening significantly predicted
      adherence to mammography screening. Adherence to mammography screening was very
      high in this sample, and enabling and need-related factors and positive views
      about mammography screening predicted adherence to mammography screening
      guidelines.

PMID- 24902465
TI  - How active are rural children and adolescents during PE class? An examination of
      light physical activity.
AB  - BACKGROUND: Few studies have examined non-exercise activity thermogenesis (NEAT)
      or light physical activity among a group of rural youth, particularly during
      physical education (PE) class. The purpose of this study was to determine whether
      the percent of PE class time spent in NEAT is related to school level (elementary
      versus high school) in a group of rural youth. METHODS: Accelerometer data from
      357 students (192 elementary, 165 high school) were included in the analysis.
      Mixed model linear regression was performed to examine the effect of school level
      on the percent of PE class time spent in NEAT. Covariates included gender, PE
      teacher, and the duration of the PE class. RESULTS: School level was a
      significant predictor of the percent of PE class time spent in NEAT.
      Specifically, elementary school students spent more of their PE class time in
      NEAT than high school students (p < .001). No other significant predictors were
      identified. CONCLUSIONS: The results of this study suggest an association between
      lower levels of light (NEAT) physical activity among high school versus
      elementary school students during PE class.

PMID- 24902467
TI  - Serious rectal bleeding complicating suction rectal biopsy in a child.
AB  - Rectal suction biopsy is the first step in evaluating suspected Hirschsprung's
      disease before a full thickness rectal biopsy is planned. It has an excellent
      safety profile and generally good yield. However, there have been rare reports of
      serious complications with this procedure and at least one death, mostly in the
      neonatal period and under one year of age, at the time of diagnosis. We report a
      case of a 2 year old child with suspected Hirschsprung's disease who underwent
      rectal suction biopsy and developed delayed bleeding requiring a blood
      transfusion. To the best of our knowledge, this is the first report of an older
      child, greater than one year of age, developing this serious complication at the
      time of rectal suction biopsy. Discussion of the technique as well as the
      patient's presentation and his outcome are provided. Pediatric
      gastroenterologists and pediatric surgeons performing rectal suction biopsy may
      need to be aware of this risk even with older children.

PMID- 24902468
TI  - Walking: a step in the right direction toward a healthier life.

PMID- 24902469
TI  - ACA rules & rates require new strategies for employers & employees.

PMID- 24902470
TI  - WVU Cancer Center study focuses on promising new lung cancer treatment.

PMID- 24902472
TI  - Characterization of skin lesions induced by skin-tropic alpha- and beta
      papillomaviruses in a patient with epidermodysplasia verruciformis.
AB  - Epidermodysplasia verruciformis (EV) is a rare, lifelong, autosomal recessive
      skin disease associated with an unusual susceptibility to infections with
      ubiquitous beta-human papillomaviruses (beta-HPVs), and in some cases also skin
      tropic alpha genotypes. In this case report, HPV infection patterns were
      correlated with pathology and clinical manifestations of skin lesions from a
      patient with EV, without loss-of-function mutations in the EVER genes. HPV
      infection was investigated by both polymerase chain reaction (PCR) and laser
      capture microdissection (LCM) PCR, alongside immunofluorescence for the viral
      proteins E4 and L1. Analysis of eyebrow hair bulbs revealed multiple beta-genus
      HPV infections, including HPV20 and HPV24, which were consistently found in all
      11 skin lesions on the patient. Six lesions were also positive for the skin
      tropic alpha-genotype, HPV27. Clear-cut differences between two wart-like
      lesions, one caused by a skin-tropic alpha-genotype and the other by beta
      genotypes (as detected by LCM PCR) are shown, including the high cellular
      proliferation rate in beta-HPV-induced lesions. Widespread expression of the
      early protein E4 was also evident in skin lesions positive for HPV20 by LCM PCR
      in both tumours and nearby intraepidermal proliferative areas. L1 expression was
      restricted to areas of intraepidermal proliferation showing productive infection.
      The patient's inability to control HPV infections is conclusive to the
      uncontrolled replication of few genotypes from both alpha and beta genera, which
      cause proliferative lesions with clear-cut clinical and histological features. 

PMID- 24902471
TI  - Putative hydrogen bond to tyrosine M208 in photosynthetic reaction centers from
      Rhodobacter capsulatus significantly slows primary charge separation.
AB  - Slow, ~50 ps, P* -> P(+)HA(-) electron transfer is observed in Rhodobacter
      capsulatus reaction centers (RCs) bearing the native Tyr residue at M208 and the
      single amino acid change of isoleucine at M204 to glutamic acid. The P* decay
      kinetics are unusually homogeneous (single exponential) at room temperature.
      Comparative solid-state NMR of [4'-(13)C]Tyr labeled wild-type and M204E RCs show
      that the chemical shift of Tyr M208 is significantly altered in the M204E mutant
      and in a manner consistent with formation of a hydrogen bond to the Tyr M208
      hydroxyl group. Models based on RC crystal structure coordinates indicate that if
      such a hydrogen bond is formed between the Glu at M204 and the M208 Tyr hydroxyl
      group, the -OH would be oriented in a fashion expected (based on the calculations
      by Alden et al., J. Phys. Chem. 1996, 100, 16761-16770) to destabilize P(+)BA(-)
      in free energy. Alteration of the environment of Tyr M208 and BA by Glu M204 via
      this putative hydrogen bond has a powerful influence on primary charge
      separation. 

PMID- 24902473
TI  - Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in
      patients with partial seizures: a randomized, double-blind, noninferiority trial.
AB  - OBJECTIVES: To assess the comparative efficacy and safety of pregabalin and
      levetiracetam for the reduction of seizure frequency in patients with partial
      seizures. METHODS: This was a randomized, double-blind, flexible-dose, parallel
      group noninferiority study of pregabalin and levetiracetam (randomized 1:1) as
      adjunctive treatment in adult patients with refractory partial seizures. The
      study included a 6-week baseline phase, 4-week dose-escalation phase, and 12-week
      maintenance phase. The primary endpoint was the proportion of patients with a >=
      50% reduction in 28-day seizure rate during the 12-week maintenance phase, as
      compared with baseline. Noninferiority of pregabalin was declared if the lower
      limit of the 95% confidence interval (CI) for the difference in responder rates
      was greater than the prespecified noninferiority margin of -12%. A key secondary
      endpoint was the percent change from baseline in 28-day seizure rate during the
      dose-escalation and maintenance phases. RESULTS: Five hundred nine patients were
      randomized to pregabalin (n = 254) or levetiracetam (n = 255) and 418 (208
      pregabalin, 210 levetiracetam) completed the maintenance phase. With both
      pregabalin and levetiracetam, the proportion of patients with a >= 50% reduction
      in 28-day seizure rate was 0.59 (difference between groups [95% CI], 0.00 [-0.08
      to 0.09]). Because the lower bound of the 95% CI was greater than the
      prespecified noninferiority margin of -12%, pregabalin was not inferior to
      levetiracetam. There was no significant difference between pregabalin and
      levetiracetam in the percent change in 28-day seizure rate (median difference
      [95% CI], 4.1 [-2.6 to 10.9], p = 0.3571). In a post hoc analysis, the proportion
      of patients who were seizure-free for the maintenance phase was lower with
      pregabalin (8.4%) than with levetiracetam (16.2%), p = 0.0155. Safety profiles
      were similar and consistent with prior trials. SIGNIFICANCE: These results
      indicate that pregabalin is noninferior, and has a similar tolerability, to
      levetiracetam as adjunctive therapy in reducing seizure frequency in patients
      with partial seizures.

PMID- 24902475
TI  - Psychiatric and neurologic risk factors for incident cases of new-onset epilepsy
      in older adults: data from U.S. Medicare beneficiaries.
AB  - OBJECTIVE: Neurologic diseases such as stroke are risk factors for new-onset
      epilepsy in older adults. Recent evidence suggests that psychiatric disorders
      independently predict epilepsy in older male veterans. Our aim was to examine the
      relationship between these disorders in a population-based study of older adults
      that also included women and minorities. METHODS: We used a national 5% random
      sample of 2005 Medicare beneficiaries including all 50 US states and Washington,
      DC. Beneficiaries were 65 years of age or older, with continuous Medicare Part A
      and Part B coverage and not in managed care plans. Epilepsy cases were identified
      from claims for physician visits, hospitalizations, and outpatient procedures. We
      used logistic regressions for the overall sample and stratified by gender to
      determine whether risk of new-onset epilepsy was associated with prior history of
      psychiatric (i.e., depression, psychosis, bipolar disorder, schizophrenia,
      posttraumatic stress disorder (PTSD), adjustment disorder, and substance
      abuse/dependence) and neurologic conditions (i.e., cerebrovascular disease,
      dementia, traumatic brain injury, brain tumor, metastatic cancer). RESULTS:
      Preexisting psychiatric disorders were significantly associated with new-onset
      epilepsy in the study population as were the neurologic conditions evaluated.
      Five of the seven psychiatric disorders examined were independently associated
      with new-onset epilepsy; substance abuse, psychosis, bipolar disorder,
      schizophrenia, and depression. Gender interaction effects were found for
      substance abuse/dependence and brain tumors. SIGNIFICANCE: Both neurologic and
      psychiatric factors significantly predicted new-onset epilepsy in a population
      based sample of male and female older adults. These results support earlier
      findings and extend the understanding of risk models for new-onset epilepsy in
      broader older adult populations.

PMID- 24902476
TI  - The possible long-term effects of early-life circadian rhythm disturbance on
      social behavior.
AB  - Sleep loss impairs brain function. As late sleep onset can reduce sleep, this
      sleep/circadian rhythm disturbance may cause brain impairment. Specific data on
      the long-term effects of sleep/circadian rhythm disturbance on subsequent brain
      function are lacking. Japan, a sleep-deprived society from infancy to adulthood,
      provides an ideal platform to investigate the association of these disturbances
      in early life with subsequent functioning. In this article, several current
      problematic behaviors among youth in Japan (dropping out from high school, school
      absenteeism, early resignation from employment, and suicide) are discussed in
      relation to early life sleep/circadian rhythm patterns. We hypothesize that daily
      habits of modern society during early stages of life produce unfavorable effects
      on brain function resulting in problematic behaviors in subsequent years. 

PMID- 24902474
TI  - CFTR potentiators partially restore channel function to A561E-CFTR, a cystic
      fibrosis mutant with a similar mechanism of dysfunction as F508del-CFTR.
AB  - BACKGROUND AND PURPOSE: Dysfunction of the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl(-) channel causes the genetic disease cystic
      fibrosis (CF). Towards the development of transformational drug therapies for CF,
      we investigated the channel function and action of CFTR potentiators on A561E, a
      CF mutation found frequently in Portugal. Like the most common CF mutation
      F508del, A561E causes a temperature-sensitive folding defect that prevents CFTR
      delivery to the cell membrane and is associated with severe disease. EXPERIMENTAL
      APPROACH: Using baby hamster kidney cells expressing recombinant CFTR, we
      investigated CFTR expression by cell surface biotinylation, and function and
      pharmacology with the iodide efflux and patch-clamp techniques. KEY RESULTS: Low
      temperature incubation delivered a small proportion of A561E-CFTR protein to the
      cell surface. Like F508del-CFTR, low temperature-rescued A561E-CFTR exhibited a
      severe gating defect characterized by brief channel openings separated by
      prolonged channel closures. A561E-CFTR also exhibited thermoinstability, losing
      function more quickly than F508del-CFTR in cell-free membrane patches and intact
      cells. Using the iodide efflux assay, CFTR potentiators, including genistein and
      the clinically approved small-molecule ivacaftor, partially restored function to
      A561E-CFTR. Interestingly, ivacaftor restored wild-type levels of channel
      activity (as measured by open probability) to single A561E- and F508del-CFTR Cl(
      ) channels. However, it accentuated the thermoinstability of both mutants in cell
      free membrane patches. CONCLUSIONS AND IMPLICATIONS: Like F508del-CFTR, A561E
      CFTR perturbs protein processing, thermostability and channel gating. CFTR
      potentiators partially restore channel function to low temperature-rescued A561E
      CFTR. Transformational drug therapy for A561E-CFTR is likely to require CFTR
      correctors, CFTR potentiators and special attention to thermostability.

PMID- 24902477
TI  - Diffuse alveolar haemorrhage and severe hypoxemia from Strongyloides stercoralis
      hyperinfection syndrome.
AB  - Strongyloides stercoralis hyperinfection syndrome is a rare, yet highly fatal
      disorder. It occurs most commonly in immunocompromised patients. We report a case
      of a 36-year-old Ethiopian female who presented with abdominal pain and
      hypotension. Shortly thereafter, she developed acute respiratory failure and
      progressed to acute respiratory distress syndrome and septic shock. She was found
      to have diffuse alveolar hemorrhage due to disseminated strongyloidiasis. We
      discuss the clinical condition of Strongyloides hyperinfection syndrome
      presenting with severe hypoxemia and complicated by severe diffuse alveolar
      hemorrhage leading to death. Similar cases in the literature are also describe. 

PMID- 24902479
TI  - Brainstem auditory evoked responses in an equine patient population: part I-
      adult horses.
AB  - BACKGROUND: Brainstem auditory evoked response has been an underused diagnostic
      modality in horses as evidenced by few reports on the subject.
      HYPOTHESIS/OBJECTIVES: To describe BAER findings, common clinical signs, and
      causes of hearing loss in adult horses. ANIMALS: Study group, 76 horses; control
      group, 8 horses. METHODS: Retrospective. BAER records from the Clinical
      Neurophysiology Laboratory were reviewed from the years of 1982 to 2013. Peak
      latencies, amplitudes, and interpeak intervals were measured when visible. Horses
      were grouped under disease categories. Descriptive statistics and a posthoc
      Bonferroni test were performed. RESULTS: Fifty-seven of 76 horses had BAER
      deficits. There was no breed or sex predisposition, with the exception of
      American Paint horses diagnosed with congenital sensorineural deafness. Eighty
      six percent (n = 49/57) of the horses were younger than 16 years of age. The most
      common causes of BAER abnormalities were temporohyoid osteoarthropathy (THO, n =
      20/20; abnormalities/total), congenital sensorineural deafness in Paint horses
      (17/17), multifocal brain disease (13/16), and otitis media/interna (4/4).
      Auditory loss was bilateral and unilateral in 74% (n = 42/57) and 26% (n = 15/57)
      of the horses, respectively. The most common causes of bilateral auditory loss
      were sensorineural deafness, THO, and multifocal brain disease whereas THO and
      otitis were the most common causes of unilateral deficits. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Auditory deficits should be investigated in horses with
      altered behavior, THO, multifocal brain disease, otitis, and in horses with
      certain coat and eye color patterns. BAER testing is an objective and noninvasive
      diagnostic modality to assess auditory function in horses.

PMID- 24902478
TI  - Contraceptive use and method preference among HIV positive women in Addis Ababa,
      Ethiopia: a cross sectional survey.
AB  - BACKGROUND: Prevention of unplanned pregnancies among people living with HIV is
      essential component of "Global Plan" even in the context of expanded access to
      highly active antiretroviral therapy (HAART). The study aimed to assess whether
      contraceptive use and method preference varied by the use of HAART among HIV
      positive women in Addis Ababa, Ethiopia. METHODS: A cross sectional facility
      based survey was conducted from June to October, 2012 information was gathered
      using interviewer administered questionnaire and document review was conducted to
      confirm HIV status and clinical review. A sample of 1418 HIV positive women
      including 770 women receiving HAART and 648 HAART-naive recruited randomly from
      different health institutions in Addis Ababa. Data were principally analyzed
      using logistic regression. RESULT: Overall, 71% women reported using
      contraception (75% among HAART users and 65% HAART naive women). Male condom and
      injectables are the most preferred contraceptive methods among both groups. The
      odds of contraceptive use among HAART users was higher (AOR 1.60, 95% CI; 1.30
      2.12) than HAART naive women. In addition to this, presence of partner (AOR 2.32,
      95% CI 1.60-3.40), disclosure of HIV status to husband (AOR 2.23; 95% CI 1.21
      4.12), presence of living children: one (AOR 1.7; 95% CI 1.03-2.40), two (AOR
      2.6; 95% CI 1.7-4.02) and three (AOR 3.3; 95% CI 1.90-5.60) respectively were
      found to be predictors of contraceptive use among HIV positive women. CONCLUSION:
      The contraceptive profile of women in the study area mainly dependent on male
      condom use, this indicates the need to better integrate tailored counseling and
      contraceptive options with care and support activities that targets HIV positive
      women. Moreover, emphasis should be given to dual contraceptive method use along
      with their regular follow up irrespective of their HAART use.

PMID- 24902480
TI  - Regional intensive care transports: a prospective analysis of distance, time and
      cost for road, helicopter and fixed-wing ambulances.
AB  - BACKGROUND: There are three different types of ambulance systems, all of which
      can manage the same secondary intensive care patient transport mission: road
      ambulance, rotor-wing ambulance, and fixed-wing ambulance. We hypothesized that
      costs for specific transport distances would differ between systems. We aimed to
      analyze distances and observed times for ambulance intensive care secondary
      transport missions together with system costs to assess this. METHODS: We
      prospectively collected data for consecutive urgent intensive care transports
      into the regional tertiary care hospital in the northern region of Sweden.
      Distances and transport times were gathered, and a cost model was generated based
      on these together with fixed and operating costs from the three different
      ambulance systems. Distance-cost and time-cost estimations were then generated
      for each transport system. RESULTS: Road ambulance cost relatively less for
      shorter distances (within 250 kilometers/155 miles) but were relatively time
      ineffective. The rotor-wing systems were most expensive regardless of distance;
      but were most time-effective up to 400-500 km (248-310 miles). Fixed-wing systems
      were more cost-effective for longer distance (300 km/186 miles), and time
      effective for transports over 500 km (310 miles). CONCLUSIONS: In summary, based
      on an economic model developed from observed regional ICU patient transports, and
      cost estimations, different ambulance system cost-distances could be compared.
      Distance-cost and time results show that helicopters can be effective up to
      moderate ICU transport distances (400-500), though are expensive to operate. For
      longer ICU patient transports, fixed-wing transport systems are both cost and
      time effective compared to helicopter-based systems.

PMID- 24902481
TI  - Implementation of a nurse-led behaviour change intervention to support medication
      taking in type 2 diabetes: beyond hypothesised active ingredients (SAMS
      Consultation Study).
AB  - BACKGROUND: Implementation of trial interventions is rarely assessed, despite its
      effects on findings. We assessed the implementation of a nurse-led intervention
      to facilitate medication adherence in type 2 diabetes (SAMS) in a trial against
      standard care in general practice. The intervention increased adherence, but not
      through the hypothesised psychological mechanism. This study aimed to develop a
      reliable coding frame for tape-recorded consultations, assessing both a priori
      hypothesised and potential active ingredients observed during implementation, and
      to describe the delivery and receipt of intervention and standard care components
      to understand how the intervention might have worked. METHODS: 211 patients were
      randomised to intervention or comparison groups and 194/211 consultations were
      tape-recorded. Practice nurses delivered standard care to all patients and
      motivational and action planning (implementation intention) techniques to
      intervention patients only. The coding frame was developed and piloted
      iteratively on selected tape recordings until a priori reliability thresholds
      were achieved. All tape-recorded consultations were coded and a random subsample
      double-coded. RESULTS: Nurse communication, nurse-patient relationship and
      patient responses were identified as potential active ingredients over and above
      the a priori hypothesised techniques. The coding frame proved reliable.
      Intervention and standard care were clearly differentiated. Nurse protocol
      adherence was good (M (SD) = 3.95 (0.91)) and competence of intervention delivery
      moderate (M (SD) = 3.15 (1.01)). Nurses frequently reinforced positive beliefs
      about taking medication (e.g., 65% for advantages) but rarely prompted problem
      solving of negative beliefs (e.g., 21% for barriers). Patients' action plans were
      virtually identical to current routines. Nurses showed significantly less patient
      centred communication with the intervention than comparison group. CONCLUSIONS:
      It is feasible to reliably assess the implementation of behaviour change
      interventions in clinical practice. The main study results could not be explained
      by poor delivery of motivational and action planning components, definition of
      new action plans, improved problem solving or patient-centred communication.
      Possible mechanisms of increased medication adherence include spending more time
      discussing it and mental rehearsal of successful performance of current routines,
      combined with action planning. Delivery of a new behaviour change intervention
      may lead to less patient-centred communication and possible reduction in overall
      trial effects. TRIAL REGISTRATION: ISRCTN30522359.

PMID- 24902482
TI  - The naturally competent strain Streptococcus thermophilus LMD-9 as a new tool to
      anchor heterologous proteins on the cell surface.
AB  - BACKGROUND: From fundamental studies to industrial processes, synthesis of
      heterologous protein by micro-organisms is widely employed. The secretion of
      soluble heterologous proteins in the extracellular medium facilitates their
      recovery, while their attachment to the cell surface permits the use of the
      recombinant host cells as protein or peptide supports. One of the key points to
      carry out heterologous expression is to choose the appropriate host. We propose
      to enlarge the panel of heterologous secretion hosts by using Streptococcus
      thermophilus LMD-9. This lactic acid bacterium has a generally recognised as safe
      status, is widely used in the manufacture of yogurts, fermented milks and
      cheeses, and is easy to transform by natural competence. This study demonstrates
      the feasibility of secretion of a heterologous protein anchored to the cell
      surface by S. thermophilus. For this, we used the cell envelope proteinase (CEP)
      PrtH of Lactobacillus helveticus CNRZ32 CIRM-BIA 103. RESULTS: Using S.
      thermophilus LMD-9 as the background host, three recombinant strains were
      constructed: i) a negative control corresponding to S. thermophilus PrtS- mutant
      where the prtS gene encoding its CEP was partially deleted; ii) a PrtH+ mutant
      expressing the L. helveticus PrtH pro-protein with its own motif (S-layer type)
      of cell-wall attachment and iii) a PrtH+WANS mutant expressing PrtH pro-protein
      with the LPXTG anchoring motif from PrtS. The PrtH+ and PrtH+WANS genes
      expression levels were measured by RT-qPCR in the corresponding mutants and
      compared to that of prtS gene in the strain LMD-9. The expression levels of both
      fused prtH CEPs genes, regardless of the anchoring motif, reached up-to more than
      76% of the wild-type prtS expression level. CEPs were sought and identified on
      the cell surface of LMD-9 wild-type strain, PrtH+ and PrtH+WANS mutants using
      shaving technique followed by peptide identification with tandem mass
      spectrometry, demonstrating that the heterologous secretion and anchoring of a
      protein of more than 200 kDa was efficient. The anchoring to the cell-wall seems
      to be more efficient when the LPXTG motif of PrtS was used instead of the S-layer
      motif of PrtH. CONCLUSIONS: We demonstrated S. thermophilus LMD-9 could
      heterologously secrete a high molecular weight protein and probably covalently
      anchor it to the cell-wall.

PMID- 24902483
TI  - Exposure time independent summary statistics for assessment of drug dependent
      cell line growth inhibition.
AB  - BACKGROUND: In vitro generated dose-response curves of human cancer cell lines
      are widely used to develop new therapeutics. The curves are summarised by
      simplified statistics that ignore the conventionally used dose-response curves'
      dependency on drug exposure time and growth kinetics. This may lead to suboptimal
      exploitation of data and biased conclusions on the potential of the drug in
      question. Therefore we set out to improve the dose-response assessments by
      eliminating the impact of time dependency. RESULTS: First, a mathematical model
      for drug induced cell growth inhibition was formulated and used to derive novel
      dose-response curves and improved summary statistics that are independent of time
      under the proposed model. Next, a statistical analysis workflow for estimating
      the improved statistics was suggested consisting of 1) nonlinear regression
      models for estimation of cell counts and doubling times, 2) isotonic regression
      for modelling the suggested dose-response curves, and 3) resampling based method
      for assessing variation of the novel summary statistics. We document that
      conventionally used summary statistics for dose-response experiments depend on
      time so that fast growing cell lines compared to slowly growing ones are
      considered overly sensitive. The adequacy of the mathematical model is tested for
      doxorubicin and found to fit real data to an acceptable degree. Dose-response
      data from the NCI60 drug screen were used to illustrate the time dependency and
      demonstrate an adjustment correcting for it. The applicability of the workflow
      was illustrated by simulation and application on a doxorubicin growth inhibition
      screen. The simulations show that under the proposed mathematical model the
      suggested statistical workflow results in unbiased estimates of the time
      independent summary statistics. Variance estimates of the novel summary
      statistics are used to conclude that the doxorubicin screen covers a significant
      diverse range of responses ensuring it is useful for biological interpretations.
      CONCLUSION: Time independent summary statistics may aid the understanding of
      drugs' action mechanism on tumour cells and potentially renew previous drug
      sensitivity evaluation studies.

PMID- 24902484
TI  - Keeping us all honest: publication ethics and AJA.

PMID- 24902485
TI  - Guest commentary: Residential aged care: the de facto hospice for New Zealand's
      older people.

PMID- 24902486
TI  - Waiting time and explant pathology in transplant recipients with hepatocellular
      carcinoma: a novel study using national data.
AB  - Risk factors for hepatocellular carcinoma (HCC) recurrence after liver
      transplantation have been well described. It has been surmised that longer time
      on the waitlist may select for tumors with a lower-risk of recurrence
      posttransplant, as patients with unfavorable tumor characteristics would be
      delisted due to tumor progression. Utilizing national explant pathology records
      from transplant recipients waitlisted with T2 HCC exception points, this study
      explored the correlation between waiting time and the development of pathologic
      HCC features associated with increased risk of tumor recurrence. Of 1976 explant
      pathology reports submitted nationally between April 8, 2012 and June 30, 2013,
      1453 (73.5%) were from recipients with automatic T2 HCC exception points. There
      was no association between pretransplant waiting time and the proportion of HCC
      explants with either: (i) a poorly differentiated tumor; (ii) macrovascular
      invasion; (iii) HCC beyond Milan or University of California San Francisco
      criteria; (iv) HCC beyond the "up-to-seven" criteria; or (v) extra-hepatic or
      lymph node involvement. Though there was a statistically significant increase in
      microvascular invasion in recipients with pretransplant waiting 6-12 months, this
      association was not seen when adjusted for United Network for Organ Sharing
      region. These findings suggest that waiting time alone may not select for tumors
      with more favorable characteristics. 

PMID- 24902488
TI  - Emotional reactivity, self-control and children's hostile attributions over
      middle childhood.
AB  - Hostile attribution bias, a child's tendency to interpret ambiguous social
      information as threatening or hostile, has been discussed as an important point
      in which social, emotional and cognitive information intersect. This study
      explores the natural changes that occur in children's hostile attributions across
      three grades during middle childhood and examines how emotional reactivity and
      self-control at third, fourth and fifth grade independently and interactively
      relate to these trajectories. Participants included 919 children whose mothers
      reported on their emotional reactivity, whose teachers reported on their self
      control and who completed an attribution bias interview, all at grades 3, 4 and
      5. Results revealed that among children with a greater tendency to make hostile
      attributions at third grade, lower self-control at third grade was associated
      with greater initial hostile attribution bias and less decline in biases over
      time. Additionally, greater emotional reactivity at fourth grade was associated
      with declines in these children's hostile attributions, but only when self
      control was also higher at fourth grade. 

PMID- 24902487
TI  - Reproductive desire in women with HIV infection in Spain, associated factors and
      motivations: a mixed-method study.
AB  - BACKGROUND: Antiretroviral therapy has created new expectations in the
      possibilities of procreation for persons living with HIV. Our objectives were to
      evaluate reproductive desire and to analyze the associated sociodemographic and
      clinical factors in HIV-infected women in the Spanish AIDS Research Network
      Cohort (CoRIS). METHODS: A mixed qualitative-quantitative approach was designed.
      Women of reproductive age (18-45) included in CoRIS were interviewed by phone,
      and data were collected between November 2010 and June 2012 using a specifically
      designed questionnaire. Reproductive desire was defined as having a desire to be
      pregnant at present or having unprotected sex with the purpose of having children
      or wanting to have children in the near future. RESULTS: Overall, 134 women were
      interviewed. Median age was 36 years (IQR 31-41), 55% were Spanish, and 35% were
      unemployed. 84% had been infected with HIV through unprotected sex, with a median
      time since diagnosis of 4.5 years (IQR 2.9-6.9). Reproductive desire was found in
      49% of women and was associated with: 1) Age (women under 30 had higher
      reproductive desire than those aged 30-39; OR = 4.5, 95% CI 1.4-14.3); 2) having
      no children vs. already having children (OR = 3.2; 1.3-7.7 3); Being an immigrant
      (OR = 2.2; 1.0-5.0); and 4) Not receiving antiretroviral treatment (OR = 3.6; 1.1
      12.1). The main reasons for wanting children were related to liking children and
      wanting to form a family. Reasons for not having children were HIV infection,
      older age and having children already. Half of the women had sought or received
      information about how to have a safe pregnancy, 87% had disclosed their
      serostatus to their family circle, and 39% reported having experienced
      discrimination due to HIV infection. CONCLUSIONS: The HIV-infected women
      interviewed in CoRIS have a high desire for children, and the factors associated
      with this desire are not fundamentally different from those of women in the
      general population. Maternity may even help them face a situation they still
      consider stigmatized and prefer not to disclose. Health-care protocols for
      handling HIV-positive women should incorporate specific interventions on sexual
      and reproductive health to help them fulfill their procreation desire and
      experience safe pregnancies.

PMID- 24902489
TI  - An immunohistochemical observations on the oviduct of the goat.
AB  - The oviduct has an important role in regulating transport of gametes and
      fertilization. The main role in these functions has a smooth muscle cells and
      ciliated epithelium lining the oviduct. All functions are under the influence of
      hormonal and nervous system. The objective of this study was
      immunohistochemically to examine the following structures: lining epithelium,
      smooth muscle cells, elastic fibres and nerve fibres. For this purpose, the
      following antibodies were used: cytokeratin 18, S-100 protein, acetylated alpha
      tubulin, smooth muscle actin, desmin and elastin. Ciliary and secretory cells of
      the lining epithelium were positive for cytokeratin 18 and S-100 protein. Cilia
      and the basal body-associated structures of ciliary cells were positive to
      acetylated alpha-tubulin. Smooth muscle cells (SMC) in mucosa and of the muscular
      layer were positive for alpha-smooth muscle actin (SMA) and desmin. High density
      of nerve fibres positively reacted to acetylated alpha-tubulin and S100 protein
      was present in the mucosa, muscular layer and serosa. Elastic fibres positive for
      elastin form a dense network at the base of the mucosal folds and in the muscle
      layer. A dense network of these fibres is accompanying the blood vessels. It is
      supposed that together with smooth muscle cells they are involved in the
      transport of ovum and in blood flow regulation.

PMID- 24902490
TI  - Tools for measuring patient safety in primary care settings using the RAND/UCLA
      appropriateness method.
AB  - BACKGROUND: The majority of patient contacts occur in general practice but
      general practice patient safety has been poorly described and under-researched to
      date compared to hospital settings. Our objective was to produce a set of patient
      safety tools and indicators that can be used in general practices in any
      healthcare setting and develop a 'toolkit' of feasible patient safety measures
      for general practices in England. METHODS: A RAND/UCLA Appropriateness Method
      exercise was conducted with a panel of international experts in general practice
      patient safety. Statements were developed from an extensive systematic literature
      review of patient safety in general practice. We used standard RAND/UCLA
      Appropriateness Method rating methods to identify necessary items for assessing
      patient safety in general practice, framed in terms of the Structure-Process
      Outcome taxonomy. Items were included in the toolkit if they received an overall
      panel median score of >= 7 with agreement (no more than two panel members rating
      the statement outside a 3-point distribution around the median). RESULTS: Of 205
      identified statements, the panel rated 101 as necessary for assessing the safety
      of general practices. Of these 101 statements, 73 covered structures or
      organisational issues, 22 addressed processes and 6 focused on outcomes.
      CONCLUSIONS: We developed and tested tools that can lead to interventions to
      improve safety outcomes in general practice. This paper reports the first attempt
      to systematically develop a patient safety toolkit for general practice, which
      has the potential to improve safety, cost effectiveness and patient experience,
      in any healthcare system.

PMID- 24902491
TI  - Hypokalemia in thyrotoxic periodic paralysis: implication for nephrology
      practice.

PMID- 24902493
TI  - On family secrets and -K.
AB  - In this paper I present a novel interpretation of family secrets. Leaning on
      Bion's concept of -K, the constitution of secrecy is interpreted in terms of
      family dynamics that actively prevent knowledge formation and mental growth.
      Family secrets are interpreted as a destructive process that attacks the family's
      truth-generating-space - the shared semiotic space within which meanings are
      constituted through family relationships. The paper explores the microstructure
      interpersonal process of -K through the analysis of Mike Leigh's movie, Secrets
      and Lies. Two scenes in the movie are used to demonstrate how -K is worked out in
      the form of a specific intersubjective semiotic endeavor that unconsciously
      blocks the process of meaning-making.

PMID- 24902492
TI  - Ethnic differences in health related quality of life for patients with type 2
      diabetes.
AB  - BACKGROUND: The objective of this study was to investigate the association
      between ethnicity and health related quality of life (HRQoL) in patients with
      type 2 diabetes. METHODS: The EuroQol EQ-5D measure was administered to 1,978
      patients with type 2 diabetes in the UK Asian Diabetes Study (UKADS): 1,486 of
      south Asian origin (Indian, Pakistani, Bangladeshi or other south Asian) and 492
      of white European origin. Multivariate regression using ordinary least square
      (OLS), Tobit, fractional logit and Censored Least Absolutes Deviations estimators
      was used to estimate the impact of ethnicity on both visual analogue scale (VAS)
      and utility scores for the EuroQol EQ-5D. RESULTS: Mean EQ-5D VAS and utility
      scores were lower among south Asians with diabetes compared to the white European
      population; the unadjusted effect on the mean EQ-5D VAS score was -7.82 (Standard
      error [SE] = 1.06, p < 0.01) and on the EQ-5D utility score was -0.06 (SE = 0.02,
      p < 0.01) (OLS estimator). After controlling for socio-demographic and clinical
      confounders, the adjusted effect on the EQ-5D VAS score was -9.35 (SE = 2.46, p <
      0.01) and on the EQ-5D utility score was 0.06 (SE = 0.04), although the latter
      was not statistically significant. CONCLUSIONS: There was a large and
      statistically significant association between south Asian ethnicity and lower EQ
      5D VAS scores. In contrast, there was no significant difference in EQ-5D utility
      scores between the south Asian and white European sub-groups. Further research is
      needed to explain the differences in effects on subjective EQ-5D VAS scores and
      population-weighted EQ-5D utility scores in this context.

PMID- 24902494
TI  - Bowel dysfunction following nerve-sparing radical hysterectomy for cervical
      cancer: a prospective study.
AB  - OBJECTIVE: To objectively assess anorectal dysfunction following nerve-sparing
      radical hysterectomy in stage I-II cervical carcinoma patients. MATERIAL AND
      METHODS: Between 2008 and 2012, 21 patients with primary cervical cancer stage
      FIGO I-II were enrolled in this prospective study. All women underwent nerve
      sparing radical hysterectomy. Anorectal manometry was performed preoperatively
      and 6 months after surgery. A paired Student t test was used to assess the
      statistical difference between the manometric evaluations. A p value <0.05 was
      considered statistically significant. RESULTS: Twenty-one patients were available
      for follow-up. Maximal and mean anal resting and squeezing pressures were
      unaffected by the surgical procedure, rectoanal inhibitory reflex and length of
      the high anal pressure zone did not change after the operation. The minimal
      volume to elicit rectal sensation, urge to defecate and maximal tolerable volume
      did not change significantly in the postoperative period, although they decreased
      in 2 and increased in 3 patients. In addition, rectal compliance did not change
      after surgery. Furthermore, no significant differences were found between
      patients who were or were not treated with adjuvant radiotherapy. CONCLUSIONS:
      Our findings suggest that nerve-sparing radical hysterectomy for cervical cancer
      does not seem to be associated with long-term anorectal dysfunction. (c) 2014 S.
      Karger AG, Basel.

PMID- 24902495
TI  - Pentanuclear heterometallic {Mn(III)(2)Ln(3)} (Ln = Gd, Dy, Tb, Ho) assemblies in
      an open-book type structural topology: appearance of slow relaxation of
      magnetization in the Dy(III) and Ho(III) analogues.
AB  - The reaction of Ln(III) nitrate and Mn(ClO4)2.6H2O salts in the presence of a
      multidentate sterically unencumbered ligand, (E)-2,2'-(2-hydroxy-3-((2
      hydroxyphenylimino)methyl)-5-methylbenzylazanediyl)diethanol (LH4) leads to the
      isolation of four isostructural pentanuclear hetereometallic complexes
      [Mn(III)2Gd3(LH)4(NO3)(HOCH3)]ClO4.NO3 (1),
      [Mn(III)2Dy3(LH)4(NO3)(HOCH3)]ClO4.NO3 (2),
      [Mn(III)2Tb3(LH)4(NO3)(HOCH3)]ClO4.NO3 (3), and
      [Mn(III)2Ho3(LH)4(NO3)(HOCH3)]ClO4.NO3 (4) with an open-book type structural
      topology. 1-4 are dicationic and crystallize in the achiral space group, P21/n. A
      total of four triply deprotonated ligands, [LH](3-), are involved in holding the
      pentameric metal framework, {Mn(III)2Ln3}. In these complexes both the lanthanide
      and the manganese(III) ions are doubly bridged, involving phenolate or ethoxide
      oxygen atoms. The magnetochemical analysis reveals the presence of global
      antiferromagnetic interactions among the spin centers at low temperatures in all
      the four compounds. AC susceptibility measurements show the presence of
      temperature dependent out-of-phase ac signal for compounds 2 and 4 indicating an
      SMM behavior. 

PMID- 24902496
TI  - Inhibitory activity of Myrtus communis oil on some clinically isolated oral
      pathogens.
AB  - OBJECTIVES: To determine the antimicrobial activities of Myrtus communis oil
      (MCO) on some oral pathogens. MATERIAL AND METHODS: Thirty strains of
      Streptococcus mutans, Aggregatibacteractinomycetemcomitans, Porphyromonas
      gingivalis and 20 strains of Streptococcus pyogenes and Candida albicans isolated
      from patients with dental caries, periodontal diseases, pharyngitis and oral
      lesions associated with artificial dentures were used for the antimicrobial
      activity of MCO. The oil was prepared by hydrodistillation procedures using a
      Clevenger apparatus. Agar disk diffusion and broth microdilution methods were
      performed on various concentrations of MCO (3.9-1,000 ug/ml) using all the
      pathogens isolated. RESULTS: All isolates were sensitive to MCO at 125-1,000
      ug/ml by agar disk diffusion producing inhibition zones of 8.1-41.25 mm in
      diameter. All of the S. pyogenes, S. mutans and C. albicans strains were
      sensitive to 62.5 ug/ml while 70% (21/30) of A. actinomycetemcomitans and 66.6%
      (20/30) of P. gingivalis were resistant to these concentrations. All S. pyogenes
      and S. mutans strains were sensitive to 31.25 ug/ml. All S. pyogenes strains were
      sensitive to 15.6 and 7.8 ug/ml of MCO. None of the clinical isolates in this
      study were sensitive to 3.9 ug/ml or to a lower concentration of oil. The minimum
      inhibitory concentrations of MCO for S. pyogenes, S. mutans, C. albicans,
      A.actinomycetemcomitans and P. gingivalis were 29.68 +/- 4.8, 31.25 +/- 0, 46.9
      +/- 16, 62.5 +/- 0 and 62.5 +/- 0 ug/ml, respectively. CONCLUSIONS: Data obtained
      in this study revealed a strong antimicrobial activity of MCO on the tested oral
      pathogens, and MCO could therefore be useful in the prevention of the related
      oral infections.

PMID- 24902497
TI  - Phase transitions in the complex plane of physical parameters.
AB  - At low temperature, a thermodynamic system undergoes a phase transition when a
      physical parameter passes through a singularity point of the free energy. This
      corresponds to the formation of a new order. At high temperature, thermal
      fluctuations destroy the order. Correspondingly, the free energy is a smooth
      function of the physical parameter and singularities only occur at complex values
      of the parameter. Since a complex valued parameter is unphysical, no phase
      transitions are expected when the physical parameter is varied. Here we show that
      the quantum evolution of a system, initially in thermal equilibrium and driven by
      a designed interaction, is equivalent to the partition function of a complex
      parameter. Therefore, we can access the complex singularity points of
      thermodynamic functions and observe phase transitions even at high temperature.
      We further show that such phase transitions in the complex plane are related to
      topological properties of the renormalization group flows of the complex
      parameters. This result makes it possible to study thermodynamics in the complex
      plane of physical parameters. 

PMID- 24902498
TI  - Psychometric properties and validation of the Italian version of the Mainz pain
      staging system as a tool for pain-patients referral selection.
AB  - RATIONALE, AIMS AND OBJECTIVES: Indications are lacking on which patient to refer
      to pain facilities. Pain-chronicity stage and outcome prognosis may be used for
      such aims. The Mainz pain-staging system (MPSS) classifies pain patients in three
      chronicity stages that respectively require more extensive management. We
      explored the psychometric and validation properties of its Italian version
      towards its application as screening/referral tool. METHODS: I-MPSS was
      administered to n=120 mixed non-cancer-pain outpatients. Psychometric analyses
      and formal validation included: content validity, by assessing the hypothesis of
      an existing relationship between the I-MPSS classes and criteria derived from an
      operational case definition of chronic pain; construct validity, by principle
      component analysis (PCA); the autonomous construct of the I-MPSS was assessed by
      the strength of the Spearman correlation between its classes and the brief pain
      inventory (BPI) items; and reliability, by applying Cronbach's alpha statistics.
      Associations between psychosocial moderators and the I-MPSS were assessed
      applying chi(2) analyses. RESULTS: Quantitative and qualitative analyses showed
      significant differences between I-MPSS classes for health care and drug
      utilization; BPI item scores significantly differed between the classes; Spearman
      correlation between I-MPSS classes and BPI items was mostly moderate or mild. PCA
      and scree test identified four components accounting for 63.7% of the variance.
      Cronbach's alpha was 0.842. CONCLUSIONS: The I-MPSS showed satisfactory
      psychometric and validation properties. With adequate feasibility, it enabled the
      screening of mixed non-cancer-pain outpatients in three chronicity/prognostic
      stages. Results are sufficient to warrant its use for a subsequent impact study
      as a prognostic model and screening tool for referring pain patients.

PMID- 24902499
TI  - Virulent Francisella tularensis destabilize host mRNA to rapidly suppress
      inflammation.
AB  - Highly virulent bacterial pathogens have evolved rapid means to suppress host
      inflammatory responses by unknown mechanisms. Here, we use virulent Francisella
      tularensis, the cause of lethal tularemia in humans, as a model to elucidate
      these mechanisms. We show that following infection of murine macrophages F.
      tularensis rapidly and selectively destabilizes mRNA containing adenylate
      uridylate-rich elements that encode for cytokines and chemokines important in
      controlling bacterial infection. Degradation of host mRNA encoding interleukin
      (IL)-1beta, IL-6 and CXCL1 did not require viable bacteria or de novo protein
      synthesis, but did require escape of intracellular organisms from endocytic
      vesicles into the host cytosol. The specific targeting of host mRNA encoding
      inflammatory cytokines and chemokines for decay by a bacterial pathogen has not
      been previously reported. Thus, our findings represent a novel strategy by which
      a highly virulent pathogen modulates host inflammatory responses critical to the
      evasion of innate immunity.

PMID- 24902500
TI  - MMP-12 and macrophage activation in acute aortic dissection.

PMID- 24902501
TI  - A possible association between SSRI drugs and alcohol dependence.

PMID- 24902502
TI  - Near fatal error in management of postoperative epidural analgesia.
AB  - INTRODUCTION: Acute pain service (APS) ensures provision of effective and safe
      postoperative pain relief. The following cases describe a potentially fatal error
      in managing patients who receive epidural analgesia postoperatively. CASE REPORT
      SUMMARY: Three patients who received 6-8 ml/hr epidural infusion of 0.1%
      levobupivacaine with 2 MUg/ml fentanyl (cocktail) developed poor arousal,
      hypopnoea and hypercarbia 16-18 hrs postoperatively. They required mechanical
      ventilation in the Intensive Care Unit (ICU) and exclusion of neurological and
      cardiac causes. Haemodynamically, they remained stable at the time of referral
      and throughout their ICU stay. All 3 patients were extubated within 24 hours
      uneventfully. DISCUSSION: Following an inquiry, it was found that all three
      epidural cocktails came from the same batch of preparation. Analysis of the
      contents revealed high concentrations of morphine without traces of
      levobupivacaine. The epidural cocktail infusion and patient-controlled analgesia
      (PCA) morphine syringes were prepared in identical 50-ml syringes at the same
      setting but were labeled separately by different personnel. CONCLUSION: A defined
      APS protocol should ensure patients' safety. If the protocol is strictly adhered
      to and with regular audits, preventable errors can be avoided. The acute pain
      service provider must be alert and responsive to warning signs of any protocol
      errors.

PMID- 24902503
TI  - Awareness about and views of parents on the off-label drug use in children.
AB  - BACKGROUND: Off-label use of drugs is widely prevalent in children mainly due to
      a limited data generated in children during drug development process. Parents
      play a critical role in giving consent for their child to participate in clinical
      trials. Very few studies have assessed the opinion of the parents regarding such
      use and permitting their child to participate in clinical trials. OBJECTIVE: In
      view of lack of information about the awareness among parents regarding both off
      label drug use in children as well as about allowing their child to participate
      in clinical research especially from a developing country, this study was
      conducted. METHODS: Adults accompanying patients in a tertiary care hospital were
      administered a validated, structured questionnaire following written informed
      consent. The questionnaire consisted of 18 items broadly divided into 5 themes -
      parental views on safety and labelled use of drugs in children, awareness of off
      label drug use in children, communication from healthcare worker about it,
      parental views on off-label drug use in children and willingness to allow their
      child to participate in a clinical trial. Chi-square or Fisher's exact
      probability test and McNemar's test were used for analysis. RESULTS: Initially, a
      majority of the participants felt that the drugs used in children in hospital
      (89.5%) and prescribed by a family physician (80.3%) were either safe or
      extremely safe while after the concept of off-label drug use is explained, a
      significant reduction in the proportion (59.3% in hospital and 59.8% by family
      physician) of parents felt the same. Only 30% parents were aware of off-label
      drug use in children. Ninety-three percent of the parents wanted to be informed
      whenever a doctor prescribes a drug in an off-label manner and a similar
      percentage felt the off-label drug use would increase the side-effects. Seventy
      three percent parents felt the off-label drug use is illegal and 57% would ask
      for change to a labelled drug in case of such prescription in their children. A
      majority of the parents would allow their child to participate in case of a life
      threatening condition (59.8%) or in case of a chronic illness (51.3%) but
      significantly less when their child is healthy. CONCLUSION: The present study has
      found a low level of awareness regarding the concept of off-label drug use in
      children amongst the public. Our study also shows that parents expect that the
      doctor explains the fact to them, although they appear to vest a large amount of
      trust in the doctor's judgement in doing the best for their sick child. Parents
      were more willing to allow their child's participation in clinical research if
      their child was seriously ill than if healthy, indicating the need to educate the
      society about the need for clinical research so that they could take more
      informed decisions.

PMID- 24902504
TI  - Sudden cardiac death & the Reverse Dodo Verdict.
AB  - Adverse effects of treatment on cardiac QT intervals were first reported 50 years
      ago. A clear link to sudden death was established, but the problem remained
      relatively unknown. The issue of treatment related effects on the heart, and the
      contribution this might make to sudden cardiac deaths in general, came more
      clearly into focus 20 years ago, linked to regulatory actions. In an era of
      polypharmacy, and mixing of prescribed and non-prescribed pharmacologically
      active agents it is now becoming increasingly clear that unanticipated cardiac
      effects may be common and a significant cause of mortality. There is likely
      underreporting and also underdiagnosis, as recognition requires a timely ECG.
      This paper proposes two methods to handle the problem. 

PMID- 24902505
TI  - The Affordable Care Act: opportunities for collaboration between doctors and
      lawyers.
AB  - BACKGROUND: In 2010, the Affordable Care Act (ACA) was signed into law. The Act
      seeks to improve the access of Americans to improved quality health care, while
      controlling the nation's escalating health care expenditures. The Act is
      scheduled for further implementation in 2014. OBJECTIVE: This article elucidates
      the opportunities and challenges that the ACA presents for constructive,
      innovative collaboration between the legal and medical professions in
      contributing to the quest for a more affordable and accessible high quality
      health care system. METHODS: The author analyzed the text of the Act, as well as
      secondary sources in the areas of law, medicine, and public health. This allowed
      for the creation of a comprehensive conceptual and empirical framework through
      which the Act could be properly analyzed and understood. RESULTS: The research
      described the pitfalls inherent in the Act, but demonstrated that the ACA
      presents more opportunities than challenges if lawyers and doctors are willing to
      work together to bring about needed social change. CONCLUSION: The article
      qualified these findings by emphasizing that doctors must learn to advocate on
      behalf of their profession if the potential benefits of the ACA are to be
      realized.

PMID- 24902506
TI  - Quality of drug label information on QT interval prolongation.
AB  - BACKGROUND: Information regarding QT-prolongation in the drug label may vary
      between products. This could lead to suboptimal risk minimization strategies.
      OBJECTIVE: To systematically assess the variation in the extent and content of
      information on QT prolongation in the summary of product characteristics (SPC) of
      recently approved medicinal products. METHODS: Drug labels of products centrally
      approved in Europe between 2006 and 2012 were screened. Of drugs including the
      term 'QT' in the SPC, the message on QT-prolongation ('no prolongation'/'unclear
      drug-QT association'/'possibly QT-prolongation'/'QT-prolongation') and the advice
      on cautionary measures pertaining to QT-prolongation in the label were examined,
      as well as their association. RESULTS: Of the 175 screened products, 44 contained
      information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT
      association': 43%, 'possibly QT-prolongation': 16%, 'QT-prolongation': 18%). 62%
      contained advices to act with caution in patients with additional risk factors
      for QT-prolongation. Products that more likely to have QT-prolonging properties
      according to the SPC provided more information on QT-prolongation in the SPC ('no
      prolongation': 10% and for the category 'QT-prolongation': 100%). CONCLUSIONS:
      The extent and content of information on QT-prolongation varies considerably
      between SPCs, and in almost half of the drugs a clear message on QT-prolongation
      was lacking in the SPC.

PMID- 24902507
TI  - Ninety-three cases of alcohol dependence following SSRI treatment.
AB  - BACKGROUND: There have been recent reports linking serotonin reuptake inhibitor
      use with increased alcohol consumption. A syndrome of alcoholism precipitated by
      a common treatment has clear implications for both research and treatment if it
      is a common phenomenon. OBJECTIVE: To explore the profile of people affected, and
      drugs that might trigger the syndrome. METHODS: We have selected reports to
      RxISK.org reporting the problem and cases linked to a blog posting outlining the
      syndrome and mined these for data on age, gender, drug of use, pattern of outcome
      on treatment, and impact of the problem. RESULTS: The data make it clear that all
      treatments with significant effects on the serotonin reuptake system are likely
      to cause this problem. Both sexes, and all ages are affected and reports have
      come from a range of countries. While stopping treatment can lead to the problem
      clearing, a failure to stop can result in death. CONCLUSIONS: SSRI induced
      alcoholism is likely to be a relatively common problem. Recognizing the problem
      can lead to a gratifying cure. A failure to recognize it can be fatal.

PMID- 24902508
TI  - One hundred and twenty cases of enduring sexual dysfunction following treatment.
AB  - BACKGROUND: There have been reports for over a decade linking serotonin reuptake
      inhibitors, finasteride and isotretinoin with enduring sexual dysfunction after
      treatment stops. OBJECTIVE: To explore the clinical pictures linked to all 3
      drugs. METHODS: We have selected 120 reports to RxISK.org reporting the problem
      and mined these for data on age, gender, drug of use, and impact of the problem.
      RESULTS: The data make it clear that the three drugs show extensive overlap in
      symptom profile, regardless of sex or country of origin. CONCLUSIONS: The
      availability of 120 reports from over 20 countries add to the case for the
      validity of the syndrome. This is severe and enduring condition can result in
      death. An understanding of its physiology and an approach to treatment are
      needed.

PMID- 24902509
TI  - Carpal pseudoerosions: a plain X-ray interpretation pitfall.
AB  - OBJECTIVE: To examine in detail images of pseudoerosion of the wrist and hand on
      plain radiographs. MATERIAL AND METHODS: The study was conducted with 28 cadaver
      wrists. During a single imaging session three techniques-plain radiography,
      tomosynthesis, and computed tomography-were used to visualize the wrist and hand
      specimens. For each technique, 20 radio-ulno-carpo-metacarpal sites known to
      present bone erosions in rheumatoid arthritis were analyzed by two radiologists
      using a standard system to score the cortical bone: normal, pseudoerosion, true
      erosion, or other pathology. Cohen's concordance analysis was performed to
      determine inter-observer and intra-observer (for the senior radiologist)
      agreement by site and by technique. Serial sections of two cadaver specimens were
      examined to determine the anatomical correlation of the pseudoerosions. RESULTS:
      On the plain radiographs, the radiologists scored many images as pseudoerosion
      (7.3%), particularly in the distal ulnar portion of the capitate, the distal
      radial portion of the hamate, the proximal ulnar portion of the base of the third
      metacarpal, the proximal radial portion of the base of the fourth metacarpal, the
      distal ulnar portion of the hamate, and the proximal portion of the base of the
      fifth metacarpal. The computed tomography scan revealed that none of these
      doubtful images corresponded to true erosions. The anatomical correlation study
      showed that these images could probably be attributed to ligament insertions,
      thinner lamina, and enhanced cortical bone transparency. CONCLUSION: Knowledge of
      the anatomical carpal localizations where pseudoerosions commonly occur is a
      necessary prerequisite for analysis of plain radiographs performed to diagnose or
      monitor rheumatoid arthritis.

PMID- 24902510
TI  - The iliotibial band in acute knee trauma: patterns of injury on MR imaging.
AB  - OBJECTIVE: To delineate the spectrum of knee injuries associated with sprains and
      tears of the distal iliotibial band (ITB). MATERIALS AND METHODS: A retrospective
      review of 200 random MRI scans undertaken for acute knee trauma was performed.
      Scans were excluded if there was a history of injury over 4 weeks from the time
      of the scan, septic arthritis, inflammatory arthropathy, previous knee surgery,
      or significant artefact. In each scan, the ITB was scored as normal, minor sprain
      (grade 1), severe sprain (grade 2), and torn (grade 3). The menisci, ligaments,
      and tendons of each knee were also assessed. RESULTS: The mean age was 27.4 years
      (range, 9-69 years) and 71.5% (n = 143) of the patients were male. The ITB was
      injured in 115 cases (57.5%). The next most common soft tissue structure injured
      was the anterior cruciate ligament (ACL) in 53.5% of cases (n = 107). Grade 1 ITB
      injury was seen in 90 of these 115 cases (45%), grade 2 injury in 20 cases, and
      grade 3 injury in only five cases. There is a significant association between ITB
      injury and ACL rupture (p < 0.05), as well as acute patellar dislocation (p <
      0.05). There were ten cases of significant posterolateral corner injury, and all
      were associated with ITB injury, including four ITB tears. Only two cases of
      isolated ITB injury were seen (1%). CONCLUSIONS: ITB injury is common in acute
      knee trauma and is associated with significant internal derangement of the knee,
      especially cruciate ligament rupture, posterolateral corner injury, and patellar
      dislocation.

PMID- 24902511
TI  - Utility of quantitative FDG-PET/CT for the detection of bone marrow involvement
      in follicular lymphoma: a histopathological correlation study.
AB  - OBJECTIVE: To determine the value of visual and quantitative (18) F-fluoro-2
      deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) for
      the detection of bone marrow involvement in follicular lymphoma, using direct
      histopathological examination at the right posterior iliac crest as reference
      standard. MATERIALS AND METHODS: This retrospective study included 22 patients
      with newly diagnosed follicular lymphoma who had undergone FDG-PET/CT before BMB
      of the right posterior iliac crest. FDG-PET/CT images were visually evaluated for
      bone marrow involvement in the right posterior iliac crest. Volumes of interest
      were placed in the right posterior iliac crest to calculate the 3D partial volume
      corrected mean standardized uptake value (cSUVmean), maximum standardized uptake
      value (SUVmax) and peak standardized uptake value (SUVpeak). RESULTS: Sensitivity
      and specificity of visual FDG-PET/CT analysis for the detection of bone marrow
      involvement in the right posterior iliac crest were 0.0 % (95 % confidence
      interval (CI): 0-32.4 %) and 100 % (95 % CI: 78.5-100 %), respectively. Areas
      under the receiver-operating characteristic curve of cSUVmean, SUVmax and SUVpeak
      for the detection of bone marrow involvement in the right posterior iliac crest
      were 0.85 (95 % CI: 0.63-0.96), 0.89 (95 % CI: 0.68-0.98) and 0.87 (95 % CI: 0.65
      0.97), respectively. Optimal cutoff values for cSUVmean, SUVmax and SUVpeak were
      1.3, 2.1 and 1.7, and yielded sensitivity and specificity combinations of 75.0 %
      and 85.7 %, 87.5 % and 85.7 % and 87.5 % and 85.7 %, respectively. CONCLUSION:
      This histopathological correlation study shows that, unlike visual interpretation
      of FDG-PET/CT images, quantitative FDG-PET/CT analysis may be beneficial in
      diagnosing bone marrow involvement by follicular lymphoma.

PMID- 24902512
TI  - Percutaneous vertebroplasty with the rotational fluoroscopy imaging technique.
AB  - OBJECTIVE: To evaluate the feasibility of the rotational angiography unit (RAU)
      as a single technique to guide percutaneous vertebroplasty (PVP). MATERIALS AND
      METHODS: Twenty-five consecutive patients (35 vertebral bodies, 20 lumbar and 15
      thoracic) were treated using RA fluoroscopy. Using a state-of-the-art flat-panel
      angiographer (Artis zee, Siemens, Erlangen, Germany), rotational acquisitions
      were obtained in all patients for immediate post-procedure 2D/3D reconstructions.
      Pre- and postoperative back pain was assessed with the visual analog scale (VAS).
      Fluoroscopy time, patient radiation dose exposure, technical success, mean
      procedure time, mean number of rotational acquisitions and procedural
      complications were recorded. All features were compared with a historical cohort
      of patients (N = 25) who underwent PVP under CT and mobile C-arm fluoroscopy
      guidance. RESULTS: In all cases, safe and accurate control of the needle
      insertion and bone-cement injection was successfully obtained with high-quality
      fluoroscopy images. One cement leakage was detected in the RAU group, and two
      leakages were detected in the CT and C-arm fluoroscopy group. Technical features
      were significantly different between the two groups (RAU vs. CT): mean procedure
      time: 38.2 min vs. 60.2 min (p = 0.02); median fluoroscopy time: 14.58 and 4.58
      min (p = 0.02); median number of rotational acquisitions: 5 vs. 10 (p = 0.02);
      mean patient dose: 6 +/- 1.3 mSv vs. 23 +/- 1.3 mSv (p = 0.02). There were minor
      complications (pain, small hematoma) in two patients (8%) in the study group and
      three cases (12%) in the control group. CONCLUSION: RAU guidance is an effective
      and safe technique for performing PVP because it reduces the procedural time and
      radiation exposure.

PMID- 24902513
TI  - A comparison of methods for teaching receptive labeling to children with autism
      spectrum disorders: a systematic replication.
AB  - Previous research has demonstrated that the conditional-only method (starting
      with a multiple-stimulus array) is more efficient than the simple-conditional
      method (progressive incorporation of more stimuli into the array) for teaching
      receptive labeling to children with autism spectrum disorders (Grow, Carr, Kodak,
      Jostad, & Kisamore,). The current study systematically replicated the earlier
      study by comparing the 2 approaches using progressive prompting with 2 boys with
      autism. The results showed that the conditional-only method was a more efficient
      and reliable teaching procedure than the simple-conditional method. The results
      further call into question the practice of teaching simple discriminations to
      facilitate acquisition of conditional discriminations.

PMID- 24902514
TI  - Zn-phthalocyanine-functionalized nanometal and nanometal-TiO2 hybrids:
      aggregation behavior and excited-state dynamics.
AB  - Dithiol-substituted Zn-phthalocyanine derivatives (TAZnPc1, TAZnPc2 and TAZnPc3)
      were synthesized and functionalized on nanometals (Au and Ag) and nanometal-TiO2
      hybrids were harnessed to cover the visible region of the absorption spectrum.
      Photophysical studies reveal that both H- and J-aggregation were present in the
      ZnPc-functionalized nanometal, and the extent of J-aggregation is superior on the
      surface of Ag nanoparticles. On the other hand, no H-aggregation was observed in
      the nanometal-TiO2 hybrid film, despite the fact that the tetra-anchoring
      derivative (TAZnPc3) shows lesser J-aggregation on the nanometal-TiO2 hybrid film
      than that of other two mono-anchoring derivatives (TAZnPc1 and TAZnPc2). Further,
      the electron injection and recombination processes were investigated by time
      resolved fluorescence and absorption spectroscopy. All the derivatives furnish
      biexponential decay on the nanometal surface. The shorter component is due to
      electron injection of ZnPc-nanometal particles and the longer component is due to
      free ZnPc. The rate of electron injection is faster for ZnPc-gold nanoparticles
      than that of silver nanoparticles, predominantly in TAZnPc1. This is due to the
      greater aggregation tendency of ZnPc derivatives on Ag nanoparticles than Au
      nanoparticles. After electron injection, the electron-transfer product (i.e. the
      radical cation of ZnPc) was observed at 600 nm. Moreover, the fluorescence of
      ZnPc derivatives on nanometal-TiO2 films was completely quenched due to the
      shuttling of electrons from ZnPc to TiO2 efficiently by metal nanoparticles. 

PMID- 24902516
TI  - Oxygen vacancy induced selective silver deposition on the {001} facets of BiOCl
      single-crystalline nanosheets for enhanced Cr(VI) and sodium pentachlorophenate
      removal under visible light.
AB  - We demonstrate that the high oxygen density characteristic of BiOCl {001} facets
      ensures the fast generation of oxygen vacancies in ethylene glycol under
      microwave irradiation, resulting in in situ nucleation and growth of Ag on the
      {001} facets of BiOCl single-crystalline nanosheets. The resulting Ag selectively
      deposited BiOCl single-crystalline nanosheets exhibit much higher reactivity and
      stability on both Cr(VI) reduction and sodium pentachlorophenate oxidation than
      the randomly deposited counterparts under visible light because of the tight
      contact between Ag and the {001} facets of BiOCl arisen from oxygen vacancy
      induced selective silver deposition.

PMID- 24902515
TI  - The effect of physical effort on voice characteristics.
AB  - BACKGROUND: Individuals using their voice intensively during physical effort are
      at risk for developing voice problems. This study was aimed at examining the
      influence of physical activity on voice characteristics. METHODS: Fourteen
      physical education students (age: 27 +/- 4.23 years) were recorded in a resting
      position, and during mild, moderate, and high exercise intensities (active
      conditions). Participants were also recorded immediately after each activity,
      while standing (recovery condition). All recordings were analyzed acoustically.
      RESULTS: A significant elevation in the fundamental frequency (F0) was observed
      with the increase in activity level (p < 0.05). For all other acoustic measures,
      a gradual increase was observed as the activity level was raised. This increase
      was statistically significant for a specific set of measures (jitter, PPQ5, and
      shimmer) during the active conditions. In most cases, significant contrasts were
      found only between the high activity level and the other levels. During the
      recovery conditions, a similar increase in values was observed. However, these
      findings failed to reach statistical significance. CONCLUSION: Findings imply
      that high levels of physical effort lead to a significant reduction in vocal
      stability and to an elevation in F0. These changes result from vocal effort and
      could therefore lead to voice disorders and pathology.

PMID- 24902517
TI  - A comparative study between local bone graft with a cage and with no cage in
      single posterior lumbar interbody fusion (PLIF): a multicenter study.
AB  - OBJECTIVE: A retrospective study was performed to compare the clinical and
      radiological results between local bone graft with a cage and without using a
      cage in patients treated with posterior lumbar interbody fusion surgery. METHODS:
      A total of 115 consecutive patients who underwent PLIF in three institutions were
      evaluated from December 2005 to December 2010. 53 patients received PLIF with
      local bone graft combined with using one PEEK cage, and 62 patients received the
      PLIF with local bone graft without using a cage. The clinical data and
      perioperative complications of the patients in the two groups were recorded.
      Preoperative and postoperative radiographs were taken to calculate the disc
      height and the interbody bony fusion rate. Functional outcome was assessed using
      the Kirkaldy-Willis criteria at the follow-up time. The results between the cage
      group and no cage group were compared. RESULTS: The mean follow-up time was 19
      months in no cage group and 18.5 months in cage group (P = 0.716). 20.9 % of
      patients (13 cases) in no cage group and 20.7 % of patients (11 cases) in cage
      group developed surgical complications perioperatively (P = 0.978). 51.6 %
      patients in no cage group got excellent functional outcome at the final follow-up
      while 54.7 % patients in cage group (P = 0.944). The mean interbody bony fusion
      time was 7.5 +/- 4.5 months in no cage group and 8 +/- 3.5 months in cage group
      (P = 0.841). According to the radiographs measurement, no significant difference
      was found for the disc height at each level between the two groups at the final
      follow-up. CONCLUSION: Local bone graft without a cage is as beneficial as that
      with a cage for PLIF. Comparing with local bone graft using a single cage, we
      believe that the purely local bone graft is a more ideal way in single PLIF.

PMID- 24902518
TI  - Irreducible dislocation of the thumb interphalangeal joint due to displaced
      flexor pollicis longus tendon: case report and new reduction technique.
AB  - Dislocation of the thumb interphalangeal (IP) joint is uncommon because of the
      inherent stability of the joint. Cases in which reduction was blocked by the
      volar plate, the flexor pollicis longus (FPL) tendon, the sesamoid bone, and an
      osteochondral fragment have been described in the literature. This article
      reports a case of closed thumb IP joint dislocation caused by the displacement of
      the FPL tendon. A new percutaneous reduction technique for this injury will also
      be presented. A 63-year-old woman presented to the emergency room with an obvious
      thumb deformity. Radiographs confirmed dorsal dislocation of the thumb IP joint
      without associated fracture. Closed reduction was not successful. Percutaneous
      reduction was performed under locoregional anesthesia, because the dislocation
      was due to an FPL tendon that had displaced dorsally and radially to the proximal
      phalanx. After reduction, Kirschner wire fixation was not needed, but IP joint
      immobilization with a splint was required for 3 weeks. Postoperatively, there
      were no complications in soft tissues and the operative scar was almost
      unrecognizable. This technique enables a mini-invasive reduction by operating
      percutaneously on the FPL. In addition, unlike with a volar zigzag approach, it
      is possible to suppress the occurrence of postoperative adhesion of the flexor
      tendon. This new minimally invasive reduction technique is useful for irreducible
      dislocation of the thumb IP joint due to a displaced FPL tendon.

PMID- 24902519
TI  - Impact of socioeconomic risk factors on the seroprevalence of cytomegalovirus
      infections in a cohort of pregnant Polish women between 2010 and 2011.
AB  - The purpose of this investigation was to perform an evaluation of the prevalence
      and socioeconomic risk factors for human cytomegalovirus (HCMV) infections in a
      cohort of Polish pregnant women between 2010 and 2011. HCMV-specific IgG and IgM
      antibody levels were assayed with enzyme-linked immunosorbent assay (ELISA) tests
      in serum samples collected from 1,250 pregnant women attending outpatient
      obstetric clinics and hospitalized at two hospitals in Lodz. The seroprevalence
      of anti-HCMV IgG and IgM antibodies was 62.4 and 2.2 %, respectively, and
      differed significantly between age-stratified groups (p <= 0.05). The highest IgG
      prevalence was observed in women above 36 years of age (76.2 %) and IgM in
      adolescent women aged 16-20 years (6.0 %). Of the various socioeconomic factors,
      age above 36 years, basic and professional education, and offspring were
      significantly associated with HCMV IgG prevalence rates (PRs; 1.89, 1.80, and
      1.56, respectively). Financial status, occupational risk related to contact with
      children, and transfusions were not related to the prevalence of IgG antibodies.
      The IgM prevalence was not associated with any of the analyzed risk factors. A
      slightly higher prevalence was observed in women who were transfused in the past,
      but the relationship was not significant. The current data have revealed a
      decrease in HCMV IgG seroprevalence in our region during recent years (62.4 vs.
      76.7 %). Basic and professional education, as well as bringing up offspring, were
      determined as significant risk factors for HCMV infections in Polish pregnant
      women [risk ratio (RR) 1.20 and 1.17, respectively], suggesting that the primary
      and secondary prophylaxis of cytomegaly is necessary during pregnancy, even if
      screening is not mandatory.

PMID- 24902521
TI  - Linezolid in the treatment of extensively drug-resistant tuberculosis.
AB  - PURPOSE: To investigate the linezolid (LZD) treatment outcome and correlation
      between in vitro susceptibility to LZD and clinical outcome. METHODS: We
      retrospectively reviewed records of tuberculosis (TB) patients who received
      treatment with linezolid between March 2012 and February 2013. RESULTS: A total
      of 43 extensively drug-resistant (XDR) TB patients identified by drug
      susceptibility testing were enrolled in this study, including 15 (34.9 %)
      received LZD as part of individualized treatment regimens. Among the 43 XDR TB
      patients, 15 patients (34.9 %) obtained favorable clinical outcome, including 9
      (60.0 %) from LZD group and 6 (21.4 %) from control group without LZD.
      Statistical analysis revealed that the percentage of favorable outcomes of LZD
      group was significantly higher than that of control group (P = 0.011).
      Furthermore, we analyzed the LZD minimum inhibitory concentrations of
      Mycobacterium tuberculosis (MTB) isolates from patients in LZD group and
      identified 4 (26.7 %) resistant to LZD. All of the patients with LZD resistance
      harbored adverse clinical outcome, while most of the patients infected with LZD
      sensitive MTB harbored favorable clinical outcome (81.8 %, 9/11). Statistical
      analysis revealed that the percentage of favorable outcome among the patients
      with LZD resistance was statistically lower than that among the LZD susceptible
      group (P = 0.011). CONCLUSION: This study demonstrates that linezolid has
      efficacy against XDR pulmonary TB patients, even in shorter duration of
      administration. The XDR TB patients infected with LZD-resistant isolates were
      more likely to obtain the adverse clinical outcome under the treatment of regimen
      containing LZD.

PMID- 24902523
TI  - Emerging pathogen: a case and review of Raoultella planticola.
AB  - Raoultella planticola has been considered a relatively harmless Gram-negative
      bacteria, rarely associated with clinical infection. However, in recent years,
      the frequency at which severe infection by R. planticola and drug-resistant
      strains are reported in literature has increased. Here, we present one case of
      acute cholecystitis caused by R. planticola, and review all previously reported
      cases of the infection in an attempt to identify new trends in biological and
      clinical features of R. planticola infections. 

PMID- 24902522
TI  - Listeria monocytogenes meningoencephalitis in adults: analysis of factors related
      to unfavourable outcome.
AB  - PURPOSE: To analyse the short-term outcome in patients with Listeria
      monocytogenes meningoencephalitis (LMME) to improve management and outcome.
      METHODS: Observational study with adult patients with LMME between 1977 and 2009
      at a tertiary hospital in Barcelona, Spain. Parameters that predicted outcome
      were assessed with univariate and logistic regression analysis. RESULTS: Of 59
      cases of LMME, 28 occurred in the last decade. Since 1987, a new protocol has
      been used and 29/45 patients (64%) treated since then received adjuvant
      dexamethasone. In patients who received this treatment there was a trend towards
      fewer neurological sequelae (5 vs 33%; p = 0.052). Antiseizure prophylaxis with
      phenytoin was administered in 13/45 (28%) patients. Seizures occurred in 7/45
      (16%) patients, all in the group who did not receive phenytoin. Hydrocephalus
      presented in 8/59 (14%). It was never present at admission and five patients
      needed neurosurgical procedures. Sequelae after 3 months were present in 8/45
      (18%), mostly cranial nerve palsy. Rhombencephalitis (RE) was related to the
      presence of neurologic sequelae (OR: 20.4, 95% CI: 1.76-236). Overall mortality
      was 14/59 (24%), 9/59 (15%) due to neurological causes related to hydrocephalus
      or seizures. Mortality was defined as early in 36% and late in 64%. In the
      multivariate analysis, independent risk factors for mortality were presence of
      hydrocephalus (OR: 17.8, 95% CI: 2.753-114) and inappropriate empirical
      antibiotic therapy (OR: 6.5, 95% CI: 1.201-35). CONCLUSIONS: Outcome of LMME may
      be improved by appropriate empirical antibiotic therapy, suspicion and careful
      management of hydrocephalus. Use of adjuvant dexamethasone or phenytoin in a
      subgroup of these patients might have a benefit.

PMID- 24902524
TI  - Moving Perspectives on Patient Competence: A Naturalistic Case Study in
      Psychiatry.
AB  - Patient competence, defined as the ability to reason, appreciate, understand, and
      express a choice is rarely discussed in patients with obsessive compulsive
      disorder (OCD), and coercive measures are seldom used. Nevertheless, a
      psychiatrist of psychologist may doubt whether OCD patients who refuse treatment
      understand their disease and the consequences of not being treated, which could
      result in tension between respecting the patient's autonomy and beneficence. The
      purpose of this article is to develop a notion of competence that is grounded in
      clinical practice and corresponds with the experiences of patients with
      obsessions and/or compulsions. We present a naturalistic case study giving both
      the patient's and the therapist's perspective based on in-depth interviews and a
      narrative analysis. The case study shows that competence is not merely an
      assessment by a therapist, but also a co-constructed reality shaped by the
      experiences and stories of patient and therapist. The patient, a medical student,
      initially told her story in a restitution narrative, focusing on cognitive
      rationality. Reconstructing the history of her disease, her story changed into a
      quest narrative where there was room for emotions, values and moral learning.
      This fitted well with the therapist's approach, who used motivational
      interventions with a view to appealing to the patient's responsibility to deal
      with her condition. We conclude that in practice both the patient and therapist
      used a quest narrative, approaching competence as the potential for practical
      reasoning to incorporate values and emotions. 

PMID- 24902520
TI  - A survey of ATRIPLA use in clinical practice as first-line therapy in HIV
      positive persons in Europe.
AB  - ATRIPLA is licensed for use only in HIV-positive persons whose viral loads <50
      for >= 3 months. We investigated the use of ATRIPLA as first-line antiretroviral
      therapy (ART) in EuroSIDA using a web-based survey performed in Autumn 2012.
      96/112 clinics (85.7 %) completed the survey. Recommendations when initiating
      first-line ART was TRUVADA plus efavirenz in 36 (37.5 %), ATRIPLA in 35 (36.5 %),
      a different first-line regimen in 12 clinics (12.5 %), and no recommendation in 7
      clinics (7.3 %). ATRIPLA was commonest in Northern (15/21 clinics; 71.4 %), and
      least common in Eastern Europe (2/31 clinics; 6.5 %; p < 0.0001). Over one-third
      of the participating clinics in this survey were using ATRIPLA as first-line
      antiretroviral therapy, despite EMA recommendations.

PMID- 24902526
TI  - Preliminary investigation: acupoint-skin conductance in stroke survivors.
AB  - It has been reported that patients with rheumatoid arthritis or asthma have skin
      conductance over the acupoints that is lower than that of their healthy
      counterparts; this has been regarded as indirect evidence of the existence of
      acupoints and the energy-based model of diseases. In order to investigate the
      potential application of acupoint-skin conductance measurement that may reflect
      pathology of ischemic stroke, the present study recruited 34 stroke survivors
      with hemiparesis, whose skin conductance of a hand acupoint and an adjacent non
      acupoint and the finger temperature in both affected and unaffected hands were
      simultaneously measured; the data revealed that the skin conductance and finger
      temperature were statistically higher in the unaffected hand than that of the
      affected, and the skin conductance of the acupoint and the non-acupoint were
      comparable in the affected and unaffected hands respectively. We attribute the
      observed drop in the skin conductance to the diminished peripheral blood flow of
      the affected hand that is signified by relatively lower finger temperature. As
      such, it should be advisable when studying skin conductance over acupoints,
      monitoring the adjacent non-acupoint skin and local vascular circulation is
      essential. 

PMID- 24902525
TI  - Herpes B virus gD interaction with its human receptor--an in silico analysis
      approach.
AB  - BACKGROUND: The glycoprotein D (gD) is essential for Herpes B virus (BV) entry
      into mammalian cells. Nectin-1, an HSV-1 gD receptor, is found to be the receptor
      which mediated BV induced cell-cell fusion, while HVEM does not mediate fusion by
      BV glycoprotein. However, the specific sequence and structural requirements of
      the BV gD for the recognition of and binding to Nectin-1 are unknown. Moreover,
      the 3D structures of BV gD and the BV gD-receptor complex have not been
      determined. In this study, we propose a reliable model of the interaction of the
      BV gD with receptor using bioinformatics tools. RESULTS: The three-dimensional
      structures of two BV gD-receptor complexes were constructed using homology
      modelling and docking strategy. Based on the models of these complexes, the BV gD
      receptor interaction patterns were calculated. The results showed that the
      interface between the BV gD and nectin-1 molecule is not geometrically
      complementary. The computed molecular interactions indicated that two terminal
      extensions were the main region of BV gD that binds to nectin-1 and that
      hydrophobic contacts between the two molecules play key roles in their
      recognition and binding. The constructed BV gD-HVEM complex model showed that
      this complex had a lower shape complementarity value and a smaller interface area
      compared with the HSV-1 gD-HVEM complex, and the number of intermolecular
      interactions between BV gD-HVEM were fewer than that of HSV-1 gD-HVEM complex.
      These results could explain why HVEM does not function as a receptor for BV gD.
      CONCLUSION: In this study, we present structural model for the BV gD in a complex
      with its receptor. Some features predicted by this model can explain previously
      reported experimental data. This complex model may lead to a better understanding
      of the function of BV gD and its interaction with receptor and will improve our
      understanding of the activation of the BV fusion and entry process.

PMID- 24902527
TI  - GDF11/myostatin and aging.

PMID- 24902528
TI  - Neurology: violence at home.

PMID- 24902529
TI  - A burst of speed for neurological research: NeuroNEXT streamlines research
      processes to encourage collaboration and make rapid advances.

PMID- 24902530
TI  - NeuroNEXT SMA biomarkers study.

PMID- 24902532
TI  - A controlled evaluation of a targeted early case detection intervention for
      reducing delay in treatment of first episode psychosis.
AB  - PURPOSE: Interventions aimed at influencing specific pathways to care may reduce
      the duration of untreated psychosis (DUP). The purpose of this study was to
      reduce delay in referral to an early intervention service following first contact
      for help seeking for psychosis in a defined urban catchment area. METHODS: Using
      a historical control design, we conducted a targeted intervention comprised of
      intensive training and education regarding first onset of psychosis and benefits
      of early intervention with all potential points of contact in pathways to care in
      a defined catchment area of a specialized early intervention (EI) service. Data
      collected on different components of DUP [help seeking (H-DUP) and referral (R
      DUP)] and demographic and clinical characteristics on patients seeking treatment
      of first episode of a psychotic (FEP) disorder accepted in the EI service for 3
      years before and 3 years after the intervention were contrasted. No other
      systemic changes occurred in this catchment area during this period. RESULTS:
      There was a significant increase in the number of cases of FEP referred to the EI
      service post-intervention from hospitals other than the parent institute, in the
      proportion with a diagnosis of affective psychosis and proportion of patients
      from a lower socioeconomic status (SES). Although largest proportion of patients
      continued to make their first contact with community services, the latter failed
      to refer cases of psychosis to the EI service despite making a large number of
      mostly non-cases (for psychosis). The intervention had no direct effect on total
      DUP, R-DUP or H-DUP. After controlling for diagnosis and SES, post-intervention,
      R-DUP remained significantly lower for patients making first contact with the
      emergency service of the parent institute. CONCLUSIONS: The intervention failed
      to reduce R-DUP for patients making contact with or referred from community
      services and most patients still used hospital resources to enter treatment at
      the EI service.

PMID- 24902533
TI  - [Bioethics in medical institutions--new custom or help? The example of clinical
      ethics consultation at a University Medical Center].
AB  - Although ethics committees are well established in the medical sciences for human
      clinical trials, animal research and scientific integrity, the development of
      clinical ethics in German hospitals started much later during the first decade of
      the twenty-first century. Clinical ethics consultation should be pragmatic and
      problem-centered and can be defined as an ethically qualified and informed
      conflict management within a given legal framework to deal with and resolve value
      driven, normative problems in the care of patients. Clinical ethics consultations
      enable shared clinical decision-making of all parties (e.g. clinicians, patients,
      family and surrogates) involved in a particular patient's care. The clinical
      ethicist does not act as an ethics expert by making independent recommendations
      or decisions; therefore, the focus is different from other medical consultants.
      Ethics consultation was first established by healthcare ethics committees (HEC)
      or clinical ethics consultation (CEC) groups which were called in to respond to
      an ethically problematic situation. To avoid ethical dilemmas or crises and to
      act preventively with regard to ethical issues in individual patients, an ethics
      liaison service is an additional option to ethics case consultations which take
      place on a regular basis by scheduled ethics rounds during the normal ward
      rounds. The presence of the ethicist offers some unique advantages: it allows
      early recognition of even minor ethical problems and accommodates the dynamics of
      ethical and clinical goal-setting in the course of patient care. Most
      importantly, regular and non-authoritative participation of the ethicist in
      normal ward rounds allows continuous ethical education of the staff within the
      everyday clinical routine. By facilitating clinical ethical decision-making, the
      ethicist seeks to empower physicians and medical staff to deal appropriately with
      ethical problems by themselves. Because of this proactive approach, the ethics
      liaison service can make a significant contribution to preventative ethics in
      reducing the number of emerging ethical problems to the satisfaction of all
      parties involved. 

PMID- 24902534
TI  - [Healthcare occupations are "different"].
AB  - Healthcare requires careful coordination of several occupations. In order to
      attain the best possible result, including effectiveness and cost-efficiency, the
      specific expertise of each of these occupations must be clearly defined.
      Healthcare occupations, physicians and nurses, are indeed professions as opposed
      to mere "jobs". They are concerned with living but ill human beings and not with
      things. Reliance on a personal capacity of judgment is a decisive aspect of
      professions. Healthcare professionals perform best if they are granted specific
      independence relative to their work. 

PMID- 24902535
TI  - [When letting-be is more important than actions. Plea for a new culture of
      dying].
AB  - The fact of "being mortal" and mortality are of an existential meaning for every
      human being. The knowledge of death and the imagination of a finiteness of life
      have a crucial impact on the whole life. Today it has become a common approach to
      plan death, to organize and to regulate it. We tend to reduce death to a duty of
      management. With this rationalization of death we try to get within distance of
      it. Active euthanasia and assisted suicide seem to be the adequate answers to
      this approach but is death really well understood if we only try to handle it
      this way? Is autonomy really the only relevant principle to respect the concerns
      of dying individuals or desperate people who want to die? This contribution
      pleads for an emphasis on a new ethics of caring, because a truly human medicine
      is not possible without caring. It shows that care does not necessarily get in
      conflict with autonomy but that it is the prerequisite for autonomy. 

PMID- 24902536
TI  - Abstracts of the 2014 Biennial Meeting of the American Society for Stereotactic
      and Functional Neurosurgery, May 31-June 3, 2014, Washington, D.C., USA.

PMID- 24902537
TI  - Memorandum on the use of information technology to improve medication safety.
AB  - BACKGROUND: Information technology in health care has a clear potential to
      improve the quality and efficiency of health care, especially in the area of
      medication processes. On the other hand, existing studies show possible adverse
      effects on patient safety when IT for medication-related processes is developed,
      introduced or used inappropriately. OBJECTIVES: To summarize definitions and
      observations on IT usage in pharmacotherapy and to derive recommendations and
      future research priorities for decision makers and domain experts. METHODS: This
      memorandum was developed in a consensus-based iterative process that included
      workshops and e-mail discussions among 21 experts coordinated by the Drug
      Information Systems Working Group of the German Society for Medical Informatics,
      Biometry and Epidemiology (GMDS). RESULTS: The recommendations address, among
      other things, a stepwise and comprehensive strategy for IT usage in medication
      processes, the integration of contextual information for alert generation, the
      involvement of patients, the semantic integration of information resources,
      usability and adaptability of IT solutions, and the need for their continuous
      evaluation. CONCLUSION: Information technology can help to improve medication
      safety. However, challenges remain regarding access to information, quality of
      information, and measurable benefits.

PMID- 24902538
TI  - Extensor tendon injury due to repetitive wrist dorsiflexion: morphological study
      of extensor retinaculum and extensor tendon.
AB  - Most etiological studies of extensor tendon injury were based on the normal
      anatomy of extensor tendon and extensor retinaculum of the wrist. Further
      understanding of the morphological changes of the extensor tendon and extensor
      retinaculum during wrist dorsiflexion might contribute to improved and more
      accurate understanding of the etiology. The morphology of the extensor tendon of
      the mid-finger and the fourth compartment of the wrist extensor retinaculum was
      studied by sonography, and the anatomy was studied in 15 extremities from 11
      young male cadavers. Compared with anatomical images, ultrasonography provides
      similar morphological observations of the extensor retinaculum of the wrist and
      extensor tendon. Ultrasonography findings revealed that as the dorsiflexion angle
      changed, the extensor retinaculum of the wrist formed different shaped trochleas.
      The trochlea guides the rotation of the extensor tendon at the wrist, but it does
      not form a sharp corner with the extensor tendon; thus, the extensor tendon is
      not compressed. As the dorsiflexion angle increased from 0 degrees  to 60 degrees
      , the length of the trochlea gradually decreases. The shortening of the trochlea
      length will lead to a smaller frictional contact area between the extensor tendon
      and the extensor retinaculum. Consequently, the friction is centralized. During
      wrist dorsiflexion, the extensor retinaculum provides a trochlea for the extensor
      tendon. Extensor tendon injury of repetitive wrist dorsiflexion might be caused
      by centralized friction at the small contact area.

PMID- 24902539
TI  - Phenoxodiol enhances the antitumor activity of gemcitabine in gallbladder cancer
      through suppressing Akt/mTOR pathway.
AB  - Gallbladder cancer is the most common and aggressive type of biliary tract cancer
      with poor prognosis due to both its inability to be detected at an early stage
      and its poor sensitivity to conventional therapies. Gemcitabine has been more and
      more widely used for the treatment of gallbladder cancer; however, the response
      rate is not satisfactory. Phenoxodiol is an isoflavone analog with antitumor
      activity against a variety of cancers. In our current work, we examined the
      effect of phenoxodiol on gallbladder cancer cells and to determine whether
      phenoxodiol can enhance the antitumor activity of gemcitabine in gallbladder
      cancer. The combined treatment of phenoxodiol and gemcitabine was more effective
      at inhibiting cell proliferation than either chemotherapeutic agent treatment
      alone. Meanwhile, phenoxodiol arrests cell cycle progression in the G0-G1 phase.
      In addition, phenoxodiol and gemcitabine inhibit the phosphorylation of PI3K/Akt
      signaling pathway as well as modulate the expression of apoptosis-relevant
      molecules. Furthermore, the antitumor effect of combination treatment with
      phenoxodiol and gemcitabine on gallbladder cancer was evaluated using a murine
      gallbladder cancer xenograft model and the results suggested that phenoxodiol
      enhanced the in vivo antitumor activity of gemcitabine. Taken together, our study
      suggested that the combination treatment with phenoxodiol and gemcitabine might
      offer optimal therapeutic benefits for patients with gallbladder cancer. 

PMID- 24902540
TI  - Quercetin potentiates the antitumor activity of rituximab in diffuse large B-cell
      lymphoma by inhibiting STAT3 pathway.
AB  - STAT3 pathway plays an important role in the growth of diffuse large B-cell
      lymphoma (DLBCL) cells. Here we investigated the antitumor activity of Quercetin,
      a flavonoid compound, in combination with rituximab in DLBCL cell lines in vitro.
      We found that Quercetin synergistically enhanced rituximab-induced growth
      inhibition and apoptosis in DLBCL cell lines. Moreover, we found Quercetin
      exerted inhibitory activity against STAT3 pathway and downregulated the
      expression of survival genes. These results suggest that combining the Quercetin
      with rituximab may present an attractive and potentially effective way for the
      treatment of DLBCL. 

PMID- 24902541
TI  - Spatial optimization in perfusion bioreactors improves bone tissue-engineered
      construct quality attributes.
AB  - Perfusion bioreactors have shown great promise for tissue engineering
      applications providing a homogeneous and consistent distribution of nutrients and
      flow-induced shear stresses throughout tissue-engineered constructs. However, non
      uniform fluid-flow profiles found in the perfusion chamber entrance region have
      been shown to affect tissue-engineered construct quality characteristics during
      culture. In this study a whole perfusion and construct, three dimensional (3D)
      computational fluid dynamics approach was used in order to optimize a critical
      design parameter such as the location of the regular pore scaffolds within the
      perfusion bioreactor chamber. Computational studies were coupled to bioreactor
      experiments for a case-study flow rate. Two cases were compared in the first
      instance seeded scaffolds were positioned immediately after the perfusion chamber
      inlet while a second group was positioned at the computationally determined
      optimum distance were a steady state flow profile had been reached. Experimental
      data showed that scaffold location affected significantly cell content and neo
      tissue distribution, as determined and quantified by contrast enhanced nanoCT,
      within the constructs both at 14 and 21 days of culture. However, gene expression
      level of osteopontin and osteocalcin was not affected by the scaffold location.
      This study demonstrates that the bioreactor chamber environment, incorporating a
      scaffold and its location within it, affects the flow patterns within the pores
      throughout the scaffold requiring therefore dedicated optimization that can lead
      to bone tissue engineered constructs with improved quality attributes.

PMID- 24902543
TI  - Electro-biocompatibility of conjugates designed by chemical similarity.
AB  - The roughness and thickness of films formed by hybrid conjugates prepared by
      coupling poly(3,4-ethylenedioxythiophene) and synthetic amino acids bearing a 3,4
      ethylenedioxythiophene group in the side chain have been significantly increased
      using a new synthetic approach. This procedure also provoked a more effective
      incorporation of the amino acid at the end of the polymer chains, as has been
      reflected by the electronic and electrochemical properties. Although the surface
      polarity of all these materials is similar to that of formamide, the
      hydrophilicity of the conjugates is higher than that of the conducting polymer.
      The surface energy of all the investigated systems is dominated by the dispersive
      component, even though the role played by the polar contribution is more
      important for the conjugates than for the conducting polymer. On the other hand,
      all the prepared materials behave as bioactive matrices. The electrochemical
      response of the conjugates coated with cells reflects the electro-compatibility
      of these two-component substrates. Thus, the ability to exchange charge
      reversibly of all conjugates increases considerably when they are coated with
      cellular monolayers, which has attributed to favorable interactions at the
      interface formed by the conjugate surface and the cellular monolayer.

PMID- 24902542
TI  - Mitochondrial DNA copy number in peripheral blood cells declines with age and is
      associated with general health among elderly.
AB  - The role of the mitochondria in disease, general health and aging has drawn much
      attention over the years. Several attempts have been made to describe how the
      numbers of mitochondria correlate with age, although with inconclusive results.
      In this study, the relative quantity of mitochondrial DNA compared to nuclear
      DNA, i.e. the mitochondrial DNA copy number, was measured by PCR technology and
      used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and
      singletons (18-93 years of age), with the majority being elderly individuals, the
      estimated mean mitochondrial DNA copy number in peripheral blood cells was
      similar for those 18-48 years of age [mean relative mtDNA content: 61.0; 95 % CI
      (52.1; 69.9)], but declined by -0.54 mtDNA 95 % CI (-0.63; -0.45) every year for
      those older than approximately 50 years of age. However, the longitudinal, yearly
      decline within an individual was more than twice as steep as observed in the
      cross-sectional analysis [decline of mtDNA content: -1.27; 95 % CI (-1.71; 
      0.82)]. Subjects with low mitochondrial DNA copy number had poorer outcomes in
      terms of cognitive performance, physical strength, self-rated health, and higher
      all-cause mortality than subjects with high mitochondrial DNA copy number, also
      when age was controlled for. The copy number mortality association can contribute
      to the smaller decline in a cross-sectional sample of the population compared to
      the individual, longitudinal decline. This study suggests that high mitochondrial
      DNA copy number in blood is associated with better health and survival among
      elderly.

PMID- 24902544
TI  - Predictive factors of disordered eating and body image satisfaction in cyprus.
AB  - OBJECTIVE: This study aimed to assess possible relationships and predictor
      variables between disordered eating attitudes and behaviors, the internalization
      of the thin ideal construct, body image satisfaction, body image investment,
      weight-related anxiety, and body mass index (BMI) among Greek-Cypriot female
      university students in Cyprus. METHOD: A total of 243 female university students
      responded to self-report measures assessing disordered eating, internalization of
      the thin ideal, body satisfaction, body image investment, and weight-related
      anxiety. RESULTS: Disordered eating was positively correlated to the
      internalization of the thin ideal, body image investment, weight-related anxiety,
      and BMI and negatively correlated with body image satisfaction. The
      internalization of the thin ideal was also positively correlated to weight
      related anxiety and body image investment and negatively correlated to body image
      satisfaction. Furthermore, weight-related anxiety and internalization of the thin
      ideal have been found to be significant predictors of disordered eating
      attitudes. DISCUSSION: Possible explanations and vulnerability factors are
      addressed, as well as implication for prevention strategies and future research.

PMID- 24902545
TI  - Chest radiography for diagnosis of tuberculosis in children: a problem of
      interpretation.

PMID- 24902546
TI  - Tuberculosis prevention and control in prisons: do we know enough?

PMID- 24902547
TI  - Chronic bronchitis: so much more than just a smoker's cough.

PMID- 24902548
TI  - Ninety years after The Magic Mountain: world literature inspired by a
      misdiagnosis, a tribute to Christian Virchow.

PMID- 24902549
TI  - Teaching chest X-ray reading for child tuberculosis suspects.
AB  - SETTING: Cape Town, South Africa. OBJECTIVE: To improve the reading of chest X
      rays (CXRs) in child tuberculosis (TB) suspects. DESIGN: We designed a reporting
      and recording form to assist in the diagnosis of childhood TB from CXRs. We then
      developed an image bank of antero-posterior and lateral CXR pairs, with each
      image pair assigned to one of four diagnostic categories. Finally, we designed
      and carried out a 1-day training course to teach clinicians how to read
      paediatric CXRs, with pre- and post-course assessments. RESULTS: Of the 27
      participants included, 17 (63%) were women. The median age was 38 years
      (interquartile range [IQR] 32.5-43.5). The median pre-training score was 16.0/30
      (IQR 13.0-18.0) and the median post-training score was 17.0 (IQR 13.5-21.0).
      Sensitivity (P = 0.09) and specificity (P = 0.06) to detect TB did not change as
      a result of the course; however, the Wilcoxon signed ranks paired-sample test
      indicated an increase in the participants' overall ability to read CXRs (P =
      0.017). CONCLUSIONS: Teaching clinicians with a 1-day training course using a
      systematic approach and a standardised form led to a limited improvement in CXR
      reading ability.

PMID- 24902550
TI  - Trends in childhood drug-resistant tuberculosis in South Africa: a window into
      the wider epidemic?
AB  - Childhood tuberculosis (TB) is a marker of TB transmission within a community. We
      present the fourth consecutive survey of children with culture-confirmed TB at a
      hospital in Cape Town, South Africa, from 2009 to 2011. In comparison to the
      previous survey, the rate of multidrug-resistant TB (MDR-TB) has stabilised and
      the human immunodeficiency virus infection rate has declined. We also report on
      the first systematic surveillance of resistance to second-line drugs. Two
      concerns following from this are the high rate (22%) of ofloxacin resistance in
      MDR-TB isolates, and the discordance between isolates with an inhA promoter
      region mutation, usually implying ethionamide (ETH) resistance, and phenotypic
      ETH results in these isolates showing ETH susceptibility. 

PMID- 24902551
TI  - Derivation of a tuberculosis screening rule for sub-Saharan African prisons.
AB  - SETTING: Lusaka Central Prison, Zambia. OBJECTIVE: To derive screening rules for
      tuberculosis (TB) using data collected during a prison-wide TB and human
      immunodeficiency virus (HIV) screening program. DESIGN: We derived rules with two
      methodologies: logistic regression and classification and regression trees
      (C&RT). We evaluated the performance of the derived rules as well as existing
      World Health Organization (WHO) screening recommendations in our cohort of
      inmates, as measured by sensitivity, specificity, and positive and negative
      predictive values. RESULTS: The C&RT-derived rule recommended diagnostic testing
      of all inmates who were underweight (defined as body mass index [BMI] < 18.5
      kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71%
      specificity. The logistic regression-derived rule recommended diagnostic testing
      of inmates who were underweight, HIV-infected or had chest pain; the logistic
      regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO
      recommendations had sensitivities that were similar to our logistic regression
      rule but had poorer specificities, resulting in a greater testing burden.
      CONCLUSION: Low BMI and HIV infection were the most robust predictors of TB in
      our inmates; chest pain was additionally retained in one model. BMI and HIV
      should be further evaluated as the basis for TB screening rules for inmates, with
      modification as needed to improve the performance of the rules.

PMID- 24902552
TI  - Tuberculosis incidence and treatment completion among Ugandan prison inmates.
AB  - BACKGROUND: The Uganda Prisons Service (UPS) is responsible for the health of
      approximately 32 500 inmates in 233 prisons. In 2008 a rapid UPS assessment
      estimated TB prevalence at 654/100 000, three times that of the general
      population (183/100 000). Although treatment programs exist, little is known
      about treatment completion in sub-Saharan African prisons. METHODS: We conducted
      a retrospective study of Ugandan prisoners diagnosed with TB from June 2011 to
      November 2012. We analyzed TB diagnosis, TB-HIV comorbidity and treatment
      completion from national registers and tracked prison transfers and releases.
      RESULTS: A total of 469 prisoners were diagnosed with TB over the 1.5-year period
      (incidence 955/100 000 person-years). Of 466 prisoners starting treatment, 48%
      completed treatment, 43% defaulted, 5% died and 4% were currently on treatment.
      During treatment, 12% of prisoners remaining in the same prison defaulted, 53% of
      transfers defaulted and 81% of those released were lost to follow-up. The odds of
      defaulting were 8.36 times greater among prisoners who were transferred during
      treatment. CONCLUSIONS: TB incidence and treatment default are high among Ugandan
      prisoners. Strategies to improve treatment completion and prevent multidrug
      resistance could include avoiding transfer of TB patients, improving
      communications between prisons to ensure treatment follow-up after transfer and
      facilitating transfer to community clinics for released prisoners.

PMID- 24902553
TI  - Interferon-gamma release assays piloted as a latent tuberculous infection
      screening tool in Canadian federal inmates.
AB  - BACKGROUND: Interferon-gamma release assays (IGRAs) may be useful in diagnosing
      latent tuberculous infection (LTBI) in inmates; however, published experience in
      these settings is limited. OBJECTIVE: To identify variables associated with IGRA
      positivity among Canadian federal inmates with positive tuberculin skin test
      (TST) results. DESIGN: On intake, TST-positive (>=10 mm) inmates were offered an
      IGRA (QuantiFERON((r))-TB Gold), and demographic and historical data were
      collected. IGRA-positive and -negative inmates were compared using the chi(2)
      test and multivariable logistic regression; the final model's goodness of fit was
      assessed using Hosmer-Lemeshow test and area under the receiver operating
      characteristic curve (AUC). RESULTS: Of 96 TST-positive inmates, 31 (32.3%) were
      IGRA-positive. Variables associated with positive IGRA were age >45 years (11/20
      vs. 20/75, P = 0.016) and previous LTBI treatment (9/20 vs. 13/55, P = 0.032) in
      univariate analysis, and being from a country with a moderate or high estimated
      tuberculosis (TB) incidence (OR 3.5, 95%CI 1.3-9.4, P = 0.013) and absence of
      bacille Calmette-Guerin (BCG) vaccination (OR 3.3, 95%CI 1.2-9.0, P = 0.017) in
      multivariable analysis. The data fit the model well, classifying the group better
      than chance alone (AUC 0.67, P = 0.007). CONCLUSION: High discordance with TST,
      particularly among BCG-vaccinated inmates and those from low TB incidence
      countries, suggest that IGRA may be useful in Canadian federal penitentiary
      screening programmes.

PMID- 24902554
TI  - Active case finding for tuberculosis among people who inject drugs on methadone
      treatment in Dar es Salaam, Tanzania.
AB  - SETTING: Active case finding is a World Health Organization (WHO) endorsed
      strategy for improving tuberculosis (TB) case detection. Despite WHO
      recommendations for active case finding among people who inject drugs (PWID), few
      studies have been published. The historical focus of case finding has been in
      populations that are human immunodeficiency virus-positive, incarcerated or at
      higher occupational risk. OBJECTIVE: We sought to examine the yield of active
      case finding among PWID newly started on methadone in Tanzania. DESIGN: Of 222
      methadone clients, 156 (70%) met with study administrators; 150 consented to
      participate, 139 (93%) of whom were male. The median age was 34 years. A symptom
      based questionnaire was developed by the investigators and administered to every
      consenting patient by a native Swahili speaker. RESULTS: Of the 150 patients
      surveyed, 16 (11%) had one or more TB symptoms and were referred for laboratory
      testing. Six new TB cases were identified in this active case finding program,
      with a prevalence of 4%. CONCLUSION: This study presents the first data on TB
      prevalence in a population of PWID in Tanzania. This prevalence is 23 times that
      of the general Tanzanian TB prevalence of 0.2%. These results have significant
      implications for TB control.

PMID- 24902555
TI  - Adherence to treatment and supervision for tuberculosis in a DOTS programme among
      pastoralists in Uganda.
AB  - OBJECTIVE: To estimate the levels of adherence to anti-tuberculosis medications
      and associated risk factors in a pastoral community practising transhumance in
      North-Eastern Uganda. DESIGN: A cross-sectional retrospective study of a cohort
      of tuberculosis (TB) patients and their community volunteers registered from
      August 2008 to July 2009. Self-reported data were collected on doses missed,
      doses not supervised, sociodemographic situation, drug availability, perceived
      drug side effects and use of the directly observed treatment (DOT) card.
      Medication adherence was defined as having ingested at least 90% of doses given,
      and supervision adherence was defined as direct observation of at least 90% of
      doses ingested. Independent predictors of medication adherence were identified
      using binary and multivariate logistic regression. RESULTS: A total of 126 TB
      patients and an equal number of community volunteers were enrolled in the study.
      Medication and supervision adherence were estimated at respectively 72% and 63%.
      Independent predictors of medication adherence were perceived drug side effects
      (adjusted odds ratio [aOR] 5.0, 95%CI 1.86-13.6), running out of drugs (aOR 5.97,
      95%CI 2.27-15.70) and DOT card not filled in (aOR 6.65, 95%CI 2.08-20.66).
      CONCLUSION: Adherence among pastoralists is less than optimal due to poor
      institutionalisation of the DOTS strategy in a pastoralist community.

PMID- 24902556
TI  - Validation of indirect tuberculosis treatment adherence measures in a resource
      constrained setting.
AB  - SETTING: Arusha, Mwanza, Mufindi and Kilosa in Tanzania. OBJECTIVE: To assess the
      test characteristics of three indirect adherence measures against a gold standard
      of direct measurements of drug intake for use in a resource-constrained setting.
      METHODS: We assessed sensitivity, specificity, positive predictive value (PPV)
      and negative predictive value (NPV), and the diagnostic odds ratio (dORs) of
      three indirect adherence measurement tools against direct measurement in urine
      using the IsoScreen assay. RESULTS: The single adherence question of missed doses
      in the last 2 days had the highest dOR (40.3) compared to the Morisky medication
      adherence scale (MMAS, 2.5) and pill counts (3.4). The sensitivities of these
      measures were respectively 97.9%, 92% and 89.6%. Specificity ranged from 46.4%
      (adherence question) to 17.9% (MMAS). The PPVs of adherence question, pill counts
      and MMAS were respectively 97.6%, 96.5% and 94.2%, while the NPVs ranged from 50%
      (adherence question) to 3.1% (MMAS). CONCLUSION: Among several instruments for
      indirect adherence measure in the routine setting of the Tanzanian National
      Tuberculosis and Leprosy Programme, a single adherence question was found to have
      the best discriminatory power. However, the single adherence question might not
      adequately identify patients who are non-adherent. Confirmatory studies are
      needed, especially in settings with low adherence rates.

PMID- 24902557
TI  - Patient costs during tuberculosis treatment in Bangladesh and Tanzania: the
      potential of shorter regimens.
AB  - OBJECTIVE: To estimate the costs incurred by patients during the intensive and
      continuation phases of the current 6-month tuberculosis (TB) regimen in
      Bangladesh and Tanzania, and thus identify potential benefits to patients of a
      shorter, 4-month treatment regimen. DESIGN: The validated Stop TB patient cost
      questionnaire was adapted and used in interviews with 190 patients in the
      continuation phase of treatment with current regimens. RESULTS: In both
      countries, overall patient costs were lower during 2 months of the continuation
      phase (US$74 in Tanzania and US$56 in Bangladesh) than during the 2 months of the
      intensive phase of treatment (US$150 and US$111, respectively). However,
      continuation phase patient costs still represented 89% and 77% of the 2-month
      average national income in the respective countries. Direct travel costs in some
      settings were kept low by local delivery system features such as community
      treatment observation. Lost productivity and costs for supplementary foods
      remained significant. CONCLUSIONS: Although it is not a straightforward exercise
      to determine the exact magnitude of likely savings, a shorter regimen would
      reduce out-of-pocket expenses incurred by patients in the most recent 2 months of
      the continuation phase and allow an earlier return to productive activities.

PMID- 24902558
TI  - Mortality of tuberculosis patients during treatment in Israel, 2000-2010.
AB  - SETTING: Tuberculosis (TB) epidemiology in Israel is similar to that reported
      from other industrialised countries where most patients are foreign-born.
      OBJECTIVES: To assess TB case fatality rate (CFR) and mortality trends during
      treatment and to identify risk factors associated with mortality. DESIGN:
      Retrospective cohort study of all TB patients in Israel diagnosed between 2000
      and 2010. Cause of death was classified by TB-specific and non-TB-specific
      causes. RESULTS: During the study period, 451 TB patients died during treatment,
      representing a CFR of 9.9%. Of these, 72.5% died due to TB-related causes, giving
      a TB-related CFR of 7.2%. Both the overall and TB-related CFR decreased over the
      study period. Risk factors for death included male sex, older age, human
      immunodeficiency virus coinfection, culture positivity and multidrug-resistant TB
      (MDR-TB). Patients aged >=65 years comprised 70% of the TB-related deaths, and
      more than half of these (54.9%) were born in the former Soviet Union, Europe
      (excluding the former Soviet Union) or the USA. CONCLUSION: Both the overall and
      TB-related CFR decreased over the study period. Physicians who treat older male
      TB patients with MDR-TB or HIV should increase the index of suspicion to include
      the possibility of a higher risk of mortality.

PMID- 24902559
TI  - Tuberculosis in the intensive care unit: a prospective observational study.
AB  - SETTING: Data on the determinants of tuberculosis (TB) mortality in the intensive
      care unit (ICU) are scarce. OBJECTIVE: To describe factors influencing outcomes
      of patients admitted with TB requiring mechanical ventilation. DESIGN: All TB
      patients admitted to the ICU of an academic hospital in South Africa from January
      2012 to May 2013 were enrolled. Disease severity was graded according to the
      Acute Physiology And Chronic Health Evaluation (APACHE II) score. Comorbid
      diagnoses, clinical features, radiological and laboratory investigations and
      outcomes were recorded. RESULTS: Of 83 patients (mean age 36.5 +/- 12.9 years; 45
      females; 44 human immunodeficiency virus [HIV] positive) admitted with pulmonary
      (n = 69) and/or extra-pulmonary (n = 37) TB, 39 died in the ICU (mortality
      44.2%), and a further 10 died during hospitalisation (in-hospital mortality
      59.0%). Few clinical parameters, special investigations or other ancillary tests
      predicted outcome. Only CD4 count <200 cells/mm(3) in HIV-co-infected patients (P
      = 0.043) and absence of lobar consolidation (P = 0.018) were associated with ICU
      mortality, whereas a high APACHE II score (22.6 vs. 18.1, P = 0.016) and
      development of renal failure (P = 0.016) were associated with hospital mortality.
      CONCLUSION: The mortality of TB patients admitted to the ICU was extremely high.
      Very few parameters were associated with poor outcome, and no single parameter
      predicted both ICU and in-patient mortality.

PMID- 24902560
TI  - A new predictive model for an improved respiratory isolation strategy in HIV
      infected patients with PTB.
AB  - SETTING: Luigi Sacco Hospital, Milan, Italy, 1 January 2000-31 December 2010.
      OBJECTIVES: To develop a predictive score for identifying human immunodeficiency
      virus (HIV) infected patients with pulmonary tuberculosis (PTB). DESIGN:
      Retrospective study based on the medical charts of HIV-infected patients admitted
      consecutively on presumption of PTB. Patients with culture-positive TB were
      included in the TB group. Culture-negative subjects formed the non-TB group. Risk
      factors for PTB were identified and a predictive model was developed. The
      diagnostic test accuracy of the derived score and that of previously developed
      scores were analysed. RESULTS: A total of 65 patients were included in the TB
      group and 505 subjects in the non-TB group. An eight-variable model (age, origin,
      alcohol use, respiratory rate, weight loss, haemoglobin, white blood cell count,
      typical chest X-ray) was derived. When compared with the different scores, this
      model showed the greatest area under the receiver operating characteristic curve
      (0.880). This score was the only one to present a negative likelihood ratio of
      <0.2, which is the threshold for giving strong diagnostic evidence against TB.
      CONCLUSIONS: This model may be useful in predicting PTB in HIV patients in low
      endemic countries. A validation study is necessary.

PMID- 24902561
TI  - Changes of FASH ultrasound findings in TB-HIV patients during anti-tuberculosis
      treatment.
AB  - Ultrasound findings of extra-pulmonary tuberculosis (TB) have been well
      described, particularly in human immunodeficiency virus (HIV) co-infected
      patients, and are often used as a basis of diagnosis in high-prevalence settings.
      Changes in findings during anti-tuberculosis treatment are less well documented.
      We present a single-centre case series of 21 TB-HIV co-infected individuals with
      typical ultrasound findings present at baseline. In 16/21 (76%) patients, all
      findings had resolved by month 3 of treatment. In patients with persistent
      ultrasound findings at 3 months, non-adherence, drug resistance, chronic disease,
      immune-reconstitution inflammatory syndrome and alternative diagnoses were
      identified. Follow-up ultrasound at month 3 may help identify high-risk cases. 

PMID- 24902562
TI  - Composite indicator: new tool for monitoring RNTCP performance in India.
AB  - India's Revised National Tuberculosis Control Programme (RNTCP) used the
      international benchmarks of 70% case detection rate and 85% treatment success
      rate among new smear-positive tuberculosis (TB) cases for assessing programme
      performance. This approach overemphasises outcomes and focuses on quantitative
      benchmarks without sufficient regard to developing systems to monitor appropriate
      programme practice to achieve a minimum standard of TB care services. The RNTCP
      has developed a novel composite indicator tool based on a logical framework
      pathway to move beyond narrow-focused outcome indicators such as case detection
      to encourage a broad-based analysis of programme implementation. The constituent
      indicators are from routinely monitored information, spanning input, process,
      output and outcome indicators across various thematic categories of the RNTCP. 

PMID- 24902564
TI  - A molecular transport medium for collection, inactivation, transport, and
      detection of Mycobacterium tuberculosis.
AB  - In many parts of the world, the diagnosis of tuberculosis (TB) has rapidly
      shifted to molecular detection and sequencing formats. The collection and
      transport of Mycobacterium tuberculosis specimens thus remains a challenging
      problem where TB is common and the infrastructure required for ensuring sample
      integrity is lacking. PrimeStore((r)) Molecular Transport Medium (MTM) addresses
      this problem, rapidly inactivating/killing M. tuberculosis while preserving
      genomic DNA even at elevated temperatures for subsequent downstream molecular
      analysis. 

PMID- 24902563
TI  - Impact of changing diagnostic criteria for smear-positive tuberculosis: a cohort
      study in Malawi.
AB  - We assessed the impact on measured burden and outcomes of the revised World
      Health Organization and Malawi guidelines reclassifying people with single
      (including 'scanty') positive smears as smear-positive pulmonary tuberculosis
      cases. In a retrospective cohort in rural Malawi, 567 (34%) of 1670 smear
      positive episodes were based on single positive smears (including 176 with scanty
      smears). Mortality rates and the proportion starting treatment were similar in
      those with two positive smears or single, non-scanty smears. Those with single
      scanty smears had higher mortality and a lower proportion starting treatment. The
      reclassification will increase the reported burden substantially, but should
      improve treatment access. 

PMID- 24902565
TI  - Prevalence of Aspergillus sensitisation in pulmonary tuberculosis-related
      fibrocavitary disease.
AB  - SETTING: Aspergillus complicates the course of healed pulmonary tuberculosis
      (PTB), causing aspergilloma and chronic pulmonary aspergillosis. Whether
      Aspergillus also causes allergic sensitisation in PTB-related fibrocavitary
      disease and bronchiectasis remains unknown. OBJECTIVE: To investigate the
      prevalence of Aspergillus sensitisation in healed fibrocavitary PTB. DESIGN: In a
      case-control design, consecutive symptomatic new referrals with PTB-related
      fibrocavitary disease underwent spirometry, Aspergillus skin test and computed
      tomography of the chest, determination of serum IgE levels (total and Aspergillus
      fumigatus-specific), serum precipitins against A. fumigatus and eosinophil count.
      Aspergillus sensitisation was defined as either a positive Aspergillus skin test
      or A. fumigatus IgE >0.35 kUA/l. RESULTS: A total of 100 subjects (50 PTB-related
      fibrocavitary disease, 50 controls) with a mean age of 40.8 years (standard
      deviation [SD] 12.2) were enrolled. Aspergillus sensitisation was present in 16
      (32%) cases and two (4%) controls. Fourteen cases (one control) had IgE values
      >1000 IU/ml, while two cases manifested eosinophilia. Aspergillus precipitins
      were positive in 13 cases (two controls); of these, 8 did not have Aspergillus
      sensitisation. The presence of airflow obstruction on spirometry was
      significantly associated with Aspergillus sensitisation on univariate analysis
      (OR 4.96, 95%CI 1.36-18.03). CONCLUSIONS: There is a high prevalence of
      Aspergillus sensitisation in PTB-related fibrocavitary disease. The clinical
      relevance and therapeutic implications of this finding require further
      investigation.

PMID- 24902566
TI  - Knowledge, attitude and perception of second-hand smoke and factors promoting
      smoking in Malaysian adolescents.
AB  - OBJECTIVE: To identify the relationship between knowledge, attitude and
      perception regarding environmental tobacco smoke (ETS) and smoking among
      Malaysian adolescents living in states with complete or partial smoke-free
      legislation (SFL). METHODS: A total of 898 respondents aged 13-14 years were
      randomly selected from 21 secondary schools. The Malay version of the modified
      Global Youth Tobacco Survey questionnaire was used. Hierarchical logistic
      regression was performed in examining predictors of smoking attempt among
      adolescents. RESULTS: Participants exposed to ETS >5 h/day were more likely to
      have smoked compared to those exposed to ETS <1 h/day (OR 4.1, 95%CI 1.03-16.0).
      Living in a state with partial SFL was associated with a two-fold increase in
      self-reported smoking attempts (OR 1.95, 95%CI 1.10-3.43) compared to living in a
      state with complete SFL. Negative attitudes and perceptions towards smoking and
      ETS exposure were linked to lower smoking attempts in states with complete SFL.
      CONCLUSIONS: Adolescents with limited ETS exposure who lived in a state with
      complete SFL were less likely to attempt smoking compared to those exposed more
      regularly to ETS and living in a state with partial SFL. Preventing adolescents
      from becoming smokers is the key to reducing national prevalence rates in
      smoking. There is a need to implement comprehensive smoke-free legislation
      nationally across Malaysia.

PMID- 24902567
TI  - Variation in the prevalence of chronic bronchitis among smokers: a cross
      sectional study.
AB  - OBJECTIVE: Given the wide variations in prevalence of chronic obstructive
      pulmonary disease observed between populations with similar levels of exposure to
      tobacco smoke, we aimed to investigate the possibility of variations in
      prevalence of chronic bronchitis (CB) between two geographically distinct smoking
      populations in rural Karnataka, India. DESIGN: The Burden of Obstructive Lung
      Disease (BOLD) questionnaire was administered to all men aged >30 years in a
      cross-sectional survey. The chi(2) and Fisher's exact tests were used to compare
      CB prevalence in the two populations. Logistic regression was used to analyse the
      impact of multiple variables on the occurrence of CB. RESULTS: Two samples of
      2322 and 2182 subjects were included in the study. In non-smokers, CB prevalence
      did not differ between the populations. However, it was significantly different
      between smoking populations (44.79% vs. 2.13%, P < 0.0001). Logistic regression
      indicated that, in addition to smoking, region, age, occupational dust exposure
      and type of house were associated with higher likelihood of CB. An interaction
      between smoking and area of residence was found (P < 0.001) and appeared to
      explain the effect of region (without interaction). CONCLUSION: A significant
      difference in CB prevalence was observed between male populations from two areas
      of Karnataka state, including when stratified by smoking status. No significant
      difference was observed between non-smokers.

PMID- 24902568
TI  - Incidence of chronic bronchitis: a prospective study in a large general
      population.
AB  - SETTING: A county in western Sweden. OBJECTIVE: To prospectively investigate the
      incidence rate of chronic bronchitis (CB) in relation to smoking, age, sex, atopy
      and asthma in a large sample of the general population. DESIGN: Subjects from a
      county in western Sweden born between 1943 and 1973, who had participated in our
      previous study in 1993, were mailed a new questionnaire in 2003. Altogether 11
      463 (72%) answered the questionnaire, which comprised items about smoking, atopy,
      respiratory symptoms and age at onset of CB symptoms. CB was defined as chronic
      productive cough for at least 3 months per year for 2 consecutive years. RESULTS:
      There were 98 new cases of CB during 1993-2003 in the study population aged 30-60
      years at follow-up. The incidence rate was 0.9/1000 person-years (py); there was
      no significant difference between women and men or different age groups. However,
      CB incidence was higher in women in relation to smoking (incidence rate ratio
      3.6, 95%CI 1.9-7.3) and in those with ever asthma (hazard ratio 5.6, 95%CI 3.5
      9.0). CONCLUSION: This prospective general population-based study shows an
      incidence rate of CB of 0.9/1000 py. Smoking and asthma were both associated with
      an increased risk of CB.

PMID- 24902569
TI  - False-positive Xpert(r) MTB/RIF assays in previously treated patients: need for
      caution in interpreting results.
AB  - Xpert((r)) MTB/RIF is the initial diagnostic test of choice for tuberculosis
      (TB). It is not known if false-positive results are more common in previously
      treated patients. We report four patients with successful treatment for TB up to
      5 years previously who presented with respiratory tract infection and were Xpert
      positive, but had negative TB cultures and clinical improvement without anti
      tuberculosis treatment. We hypothesise that the Xpert results were false-positive
      due to the presence of dead Mycobacterium tuberculosis bacilli in lungs and
      sputum. Further work is required to determine the specificity of Xpert in
      previously treated patients. 

PMID- 24902570
TI  - ECMO: an alternative support for acute respiratory failure caused by
      tuberculosis?
AB  - Late diagnosis of tuberculosis (TB) may result in the development of severe acute
      respiratory failure. High mortality rates with conventional ventilation have been
      reported. Extracorporeal membrane oxygenation (ECMO) may represent an effective
      alternative treatment. We report a case of complicated pulmonary TB in a man who
      successfully underwent 3 months of ECMO. 

PMID- 24902579
TI  - The local kinetic energy profile of an inverted carbon-carbon bond reveals and
      refines its charge-shift character.
AB  - Analysis of the kinetic energy density within a molecule identifies patterns in
      its electronic structure that are linked to the concept of charge-shift bonding.
      This is illustrated in a detailed study of twelve molecules, possessing carbon
      carbon covalent as well as carbon-carbon charge-shift bonds in various degrees of
      orders, including propellanes and heteropropellanes. Regions of slow electrons
      are fundamental for such a correlation, and a RoSE (region of slow electrons)
      indicator nu(+/-), based on the positive definite kinetic energy density tau, is
      employed to characterize classes of charge-shift bonds in terms of its full
      topology of all critical points of rank three.

PMID- 24902578
TI  - A rare case report of subcutaneous phaeohyphomycotic cyst caused by Exophiala
      oligosperma in an immunocompetent host with literature review.
AB  - We report a rare case of phaeohyphomycotic cyst in an immunocompetent patient
      caused by Exophiala oligosperma. This fungus is earlier known to cause infections
      in the immunocompromised. Identification of black fungi at species level is more
      challenging by conventional methods, and hence final identification of the fungi
      was based on sequencing of rDNA. The patient was managed with surgical excision.
      To the best of our knowledge, this is the first case report of E. oligosperma
      human infection from India.

PMID- 24902580
TI  - Long term outcome of multidrug-resistant TB patients in Fukujuji Hospital in
      Japan.
AB  - OBJECTIVE: To present the long-term outcome of multidrug-resistant tuberculosis
      (MDR TB) patients. METHODS: An observational study of 291 MDR TB cases that were
      diagnosed from 1990 to 2011 at the Fukujuji Hospital in Japan. RESULTS: The
      frequency of relapse after cure was 3/168 (1.8%) during a mean follow-up of 4.4
      years. Among 16 failure cases, eight patients were negative in later years. One
      case among the nine lost-to-follow-up patients with culture conversion returned
      1.5 years later with positive culture. CONCLUSIONS: Chronic-positive patients
      remain positive for years and require observation. Lost to follow-up cases may
      relapse.

PMID- 24902581
TI  - NICE recommendation on the use of pressure ulcer risk scores is flawed.

PMID- 24902582
TI  - Prevalence and risk factors for foot and ankle musculoskeletal disorders
      experienced by nurses.
AB  - BACKGROUND: Nurses are at high risk of musculoskeletal disorders (MSDs). Although
      the prevalence of MSDs of the lower back, upper limbs, neck and shoulders have
      been reported previously in nursing, few studies have evaluated MSDs of the foot
      and ankle. This study evaluated the prevalence of foot and ankle MSDs in nurses
      and their relation to individual and workplace risk factors. METHODS: A self
      administered survey incorporating the Nordic Musculoskeletal Questionnaire (NMQ)
      was distributed, over a nine-week period, to all eligible nurses (n = 416)
      working in a paediatric hospital in Brisbane, Australia. The prevalence of MSDs
      for each of the NMQ body regions was determined. Bivariate and multivariable
      logistic regression analyses were conducted to examine the relationships between
      activity-limiting foot/ankle MSDs and risk factors related to the individual
      (age, body mass index, number of existing foot conditions, smoking history,
      general physical health [SF36 Physical Component Scale], footwear features) or
      the workplace (level of nursing position, work location, average hours worked,
      hours worked in previous week, time since last break from work). RESULTS: A 73%
      response rate was achieved with 304 nurses completing surveys, of whom 276 were
      females (91%). Mean age of the nurses was 37 years (+/-10), younger than the
      state average of 43 years. Foot/ankle MSDs were the most prevalent conditions
      experienced by nurses during the preceding seven days (43.8%, 95% CI 38.2-49.4%),
      the second most prevalent MSDs to impair physical activity (16.7%, 95% CI 13.0
      21.3%), and the third most prevalent MSD, after lower-back and neck problems,
      during the preceding 12 months (55.3%, 95% CI 49.6-60.7%). Of the nurse and work
      characteristics investigated, obesity, poor general physical health, existing
      foot conditions and working in the intensive care unit emerged as statistically
      significant (p < 0.05) independent risk factors for activity-limiting foot/ankle
      MSDs. CONCLUSIONS: Foot/ankle MSDs are common in paediatric hospital nurses and
      resulted in physical activity limitations in one out of every six nurses. We
      recommend targeted education programs regarding the prevention, self-management
      and treatment strategies for foot/ankle MSDs. Further research is needed into the
      impact of work location and extended shift durations on foot/ankle MSDs.

PMID- 24902584
TI  - The novel GLP-1-gastrin dual agonist ZP3022 improves glucose homeostasis and
      increases beta-cell mass without affecting islet number in db/db mice.
AB  - Antidiabetic treatments aiming to preserve or even to increase beta-cell mass are
      currently gaining increased interest. Here we investigated the effect of chronic
      treatment with the novel glucagon-like peptide-1 (GLP-1)-gastrin dual agonist
      ZP3022 (HGEGTFTSDLSKQMEEEAVRLFIEWLKN-8Ado-8Ado-YGWLDF-NH2) on glycemic control,
      beta-cell mass and proliferation, and islet number. Male db/db mice were treated
      with ZP3022, liraglutide, or vehicle for 2, 4, or 8 weeks, with terminal
      assessment of hemoglobin A1c, basal blood glucose, and plasma insulin
      concentrations. Pancreata were removed for immunohistochemical staining and
      stereological quantification of beta-cell mass, islet numbers, proliferation, and
      apoptosis. Treatment with ZP3022 or liraglutide led to a significant improvement
      in glycemic control. ZP3022 treatment resulted in a sustained increase in beta
      cell mass after 4 and 8 weeks of treatment, whereas the effect of liraglutide was
      transient. The expansion in beta-cell mass observed in the ZP3022-treated mice
      appeared to be driven by increased beta-cell proliferation in existing islets
      rather than by formation of new islets, as mean islet mass increased but the
      number of islets remained constant. Our data demonstrate that the GLP-1-gastrin
      dual agonist ZP3022 causes a sustained improvement in glycemic control
      accompanied by an increase in beta-cell mass, increased proliferation, and
      increased mean islet mass. The results highlight that the GLP-1-gastrin dual
      agonist increases beta-cell mass more than liraglutide and that dual agonists
      could potentially be developed into a new class of antidiabetic treatments. 

PMID- 24902583
TI  - Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic
      metabolite signatures during enteric fever.
AB  - The host-pathogen interactions induced by Salmonella Typhi and Salmonella
      Paratyphi A during enteric fever are poorly understood. This knowledge gap, and
      the human restricted nature of these bacteria, limit our understanding of the
      disease and impede the development of new diagnostic approaches. To investigate
      metabolite signals associated with enteric fever we performed two dimensional gas
      chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from
      patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls,
      identifying 695 individual metabolite peaks. Applying supervised pattern
      recognition, we found highly significant and reproducible metabolite profiles
      separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a
      combination of six metabolites could accurately define the etiological agent. For
      the first time we show that reproducible and serovar specific systemic biomarkers
      can be detected during enteric fever. Our work defines several biologically
      plausible metabolites that can be used to detect enteric fever, and unlocks the
      potential of this method in diagnosing other systemic bacterial infections. 

PMID- 24902585
TI  - Mass spectrometric characterization of circulating covalent protein adducts
      derived from a drug acyl glucuronide metabolite: multiple albumin adductions in
      diclofenac patients.
AB  - Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites
      are hypothetical causes of hypersensitivity reactions associated with certain
      carboxylate drugs. The complex rearrangements and reactivities of drug AG have
      been defined in great detail, and protein adducts of carboxylate drugs, such as
      diclofenac, have been found in liver and plasma of experimental animals and
      humans. However, in the absence of definitive molecular characterization, and
      specifically, identification of signature glycation conjugates retaining the
      glucuronyl and carboxyl residues, it cannot be assumed any of these adducts is
      derived uniquely or even fractionally from AG metabolites. We have therefore
      undertaken targeted mass spectrometric analyses of human serum albumin (HSA)
      isolated from diclofenac patients to characterize drug-: derived structures and,
      thereby, for the first time, have deconstructed conclusively the pathways of
      adduct formation from a drug AG and its isomeric rearrangement products in vivo.
      These analyses were informed by a thorough understanding of the reactions of HSA
      with diclofenac AG in vitro. HSA from six patients without drug-: related
      hypersensitivities had either a single drug-: derived adduct or one of five
      combinations of 2-8 adducts from among seven diclofenac N-acylations and three AG
      glycations on seven of the protein's 59 lysines. Only acylations were found in
      every patient. We present evidence that HSA modifications by diclofenac in vivo
      are complicated and variable, that at least a fraction of these modifications are
      derived from the drug's AG metabolite, and that albumin adduction is not
      inevitably a causation of hypersensitivity to carboxylate drugs or a coincidental
      association. 

PMID- 24902586
TI  - Left atrial passive emptying function determined by cardiac magnetic resonance
      predicts atrial fibrillation recurrence after pulmonary vein isolation.
AB  - BACKGROUND: Although pulmonary vein isolation has become a mainstream therapy for
      selected patients with atrial fibrillation (AF), late recurrent AF is common and
      its risk factors remain poorly defined. The purpose of our study was to test the
      hypothesis that reduced left atrial passive emptying function (LAPEF) as
      determined by cardiac magnetic resonance has a strong association with late
      recurrent AF after pulmonary vein isolation. METHODS AND RESULTS: Three hundred
      forty-six patients with AF referred for cardiac magnetic resonance pulmonary vein
      mapping before pulmonary vein isolation were included. Maximum LA volumes
      (VOLmax) and volumes before atrial contraction (VOLbac) were measured; LAPEF was
      calculated as (VOLmax-VOLbac)/VOLmax*100. Kaplan-Meier curves were constructed to
      determine late recurrent AF stratified by LAPEF quintile. Cox proportional
      hazards regression was used to adjust for known markers of recurrence. During a
      median follow-up of 27 months, 124 patients (35.8%) experienced late recurrent
      AF. Patients with recurrence were more likely to have nonparoxysmal AF (75.8%
      versus 51.4%; P<0.01), higher mean VOLmax (60.2 versus 52.8 mL/m(2); P<0.01), and
      lower mean LAPEF (19.1% versus 26.0%; P<0.01). Patients in the lowest LAPEF
      quintile were at highest risk of developing recurrent AF (2-year recurrence for
      lowest versus highest: 60.5% versus 17.3%; P<0.01). After adjusting for known
      predictors of recurrence, patients with low LAPEF remained significantly more
      likely to recur (hazard ratio for lowest versus highest quintile, 3.92; 95%
      confidence interval, 2.01-7.65). CONCLUSIONS: We found a strong association
      between LAPEF and recurrent AF after pulmonary vein isolation that persisted
      after multivariable adjustment.

PMID- 24902587
TI  - Prevalence of myocardial fibrosis patterns in patients with systolic dysfunction:
      prognostic significance for the prediction of sudden cardiac arrest or
      appropriate implantable cardiac defibrillator therapy.
AB  - BACKGROUND: Late gadolinium enhancement-cardiac magnetic resonance is
      increasingly performed in patients with systolic dysfunction. Numerous patterns
      of fibrosis are commonly reported among this population. However, the relative
      prevalence and prognostic significance of these findings remains uncertain.
      METHODS AND RESULTS: Three hundred eighteen consecutive patients referred for
      late gadolinium enhancement-cardiac magnetic resonance and a left ventricular
      ejection fraction <55% were followed up for the primary end point of sudden
      cardiac arrest or appropriate implantable cardiac defibrillator therapy. Late
      gadolinium enhancement images were blindly interpreted for the presence of 6
      distinct pattern(s) of myocardial fibrosis in addition to signal threshold-based
      quantification of total fibrosis volume. The mean age and left ventricular
      ejection fraction of participants were 62.0+/-12.9 years and 32.6+/-11.9%,
      respectively. Any pattern of myocardial fibrosis was seen in 248 patients (78%)
      with >=2 patterns present in 25% of patients. During follow-up (median of 467
      days), 49 patients (15%) had a primary outcome. After adjustment for left
      ventricular ejection fraction, cardiomyopathy pathogenesis, and total fibrosis
      volume, the presence of a midwall striae pattern of fibrosis was an independent
      predictor of sudden cardiac arrest or appropriate implantable cardiac
      defibrillator therapy with a hazard ratio of 2.4 (95% confidence interval, 1.2
      4.6; P=0.01); this finding is present in 30% of patients with nonischemic and 15%
      of patients with ischemic cardiomyopathy. Cumulative event rate was significantly
      higher among those with midwall striae, particularly among those with a left
      ventricular ejection fraction >35% (40% versus 6%; P=0.005). CONCLUSIONS:
      Patients with systolic dysfunction frequently demonstrate multiple patterns of
      myocardial fibrosis. Of these, a midwall striae pattern of fibrosis is the
      strongest independent predictor of sudden cardiac arrest or appropriate
      implantable cardiac defibrillator therapy.

PMID- 24902588
TI  - Do bisphosphonates affect bone healing? A meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Whether bisphosphonates affect indirect bone healing is still
      unclear. METHOD: We carried out a comprehensive search strategy. Only randomized
      controlled trials were included. Two reviewers independently assessed
      methodological qualities and extracted outcome data. Analysis was performed with
      RevMan 5.2. RESULTS: Eight eligible randomized controlled trials with 2,508
      patients were included. Meta-analysis results showed that no statistically
      significant differences were founded in indirect bone healing in short time
      (within 3 months) (relative risk (RR) 1.40, relative the control group; 95% CI
      0.36 to 5.49) and in long-term (more than 12 months) postoperation (RR 1.0; 95%
      CI 0.98 to 1.02) between bisphosphonates infusion groups and control groups.
      There were no statistically significant differences of indirect bone healing
      between early and delay bisphosphonates administration groups. Bisphosphonates
      infusion after lumbar infusion surgery could promote bone healing and shorten
      fusion time in 6 months postoperation (RR 1.35; 95% CI 1.11 to 1.66). CONCLUSION:
      There was no clinically detectable delay to fracture healing via external callus
      formation following bisphosphonates treatment. Considering the benefit aspects of
      bisphosphonates for osteoporosis treatment, we recommend bisphosphonates infusion
      after fracture fixation surgery and lumbar fusion surgery.

PMID- 24902589
TI  - A clinical protocol to increase chewing and assess mastication in children with
      feeding disorders.
AB  - Children with feeding disorders often cannot or do not chew when presented with
      table food. Children with chewing deficits also often swallow the bite before
      masticating it appropriately, which we will refer to as early swallowing. In the
      current study, we evaluated a clinical protocol to increase chews per bite,
      assess mastication, and eliminate early swallowing with three children with
      feeding disorders. The current study adds to a small body of literature on
      chewing and mastication of children with feeding disorders. Suggestions for
      future research are also discussed. 

PMID- 24902590
TI  - The influence of the design matrix on treatment effect estimates in the
      quantitative analyses of single-subject experimental design research.
AB  - The quantitative methods for analyzing single-subject experimental data have
      expanded during the last decade, including the use of regression models to
      statistically analyze the data, but still a lot of questions remain. One question
      is how to specify predictors in a regression model to account for the specifics
      of the design and estimate the effect size of interest. These quantitative effect
      sizes are used in retrospective analyses and allow synthesis of single-subject
      experimental study results which is informative for evidence-based decision
      making, research and theory building, and policy discussions. We discuss
      different design matrices that can be used for the most common single-subject
      experimental designs (SSEDs), namely, the multiple-baseline designs, reversal
      designs, and alternating treatment designs, and provide empirical illustrations.
      The purpose of this article is to guide single-subject experimental data analysts
      interested in analyzing and meta-analyzing SSED data. 

PMID- 24902591
TI  - Disease-associated QT-shortage versus quinine associated QT-prolongation: age
      dependent ECG-effects in Ghanaian children with severe malaria.
AB  - BACKGROUND: While several anti-malarials are known to affect the electric
      conduction system of the heart, less is known on the direct effects of Plasmodium
      falciparum infection. Some earlier studies point to a direct impact of Plasmodium
      falciparum infection on the electric conduction system of the heart. The aim of
      this study was to analyse infection- and drug-induced effects on the electric
      conduction system. METHODS: Children aged 12 months to 108 months with severe
      malaria were included in Kumasi, Ghana. In addition to basic demographic,
      clinical, biochemical and parasitological, biochemical data were measured data
      upon hospitalization (day 0) and 12-lead electrocardiograms were recorded before
      (day 0) and after (day 1) initiation of quinine therapy as well as after 42 (+/
      3) days. RESULTS: A total of 180 children were included. Most children were
      tachycardic on day 0 but heart rate declined on day 1 and during follow up. The
      corrected QT intervals were longest on day 1 and shortest on day 0. Comparison of
      QT intervals with day 42 (healthy status) after stratification for age
      demonstrated that in the youngest (<24 months) this was mainly due to a QT
      shortage on day 0 while a QT prolongation on day 1 was most pronounced in the
      oldest (>=48 months). Nearly one third of the participating children had
      measurable 4-aminoquinoline levels upon admission, but no direct effect on the
      corrected QT intervals could be shown. CONCLUSION: Severe P. falciparum infection
      itself can provoke changes in the electrophysiology of the heart, independent of
      anti-malarial therapy. Especially in young - thus non immune - children the
      effect of acute disease associated pre-treatment QT-shortage is more pronounced
      than quinine associated QT-prolongation after therapy. Nevertheless, neither
      malaria nor anti-malarial induced effects on the electrophysiology of the heart
      were associated with clinically relevant arrhythmias in the present study
      population.

PMID- 24902592
TI  - A semi-automated technique for labeling and counting of apoptosing retinal cells.
AB  - BACKGROUND: Retinal ganglion cell (RGC) loss is one of the earliest and most
      important cellular changes in glaucoma. The DARC (Detection of Apoptosing Retinal
      Cells) technology enables in vivo real-time non-invasive imaging of single
      apoptosing retinal cells in animal models of glaucoma and Alzheimer's disease. To
      date, apoptosing RGCs imaged using DARC have been counted manually. This is time
      consuming, labour-intensive, vulnerable to bias, and has considerable inter- and
      intra-operator variability. RESULTS: A semi-automated algorithm was developed
      which enabled automated identification of apoptosing RGCs labeled with
      fluorescent Annexin-5 on DARC images. Automated analysis included a pre
      processing stage involving local-luminance and local-contrast "gain control", a
      "blob analysis" step to differentiate between cells, vessels and noise, and a
      method to exclude non-cell structures using specific combined 'size' and 'aspect'
      ratio criteria. Apoptosing retinal cells were counted by 3 masked operators,
      generating 'Gold-standard' mean manual cell counts, and were also counted using
      the newly developed automated algorithm. Comparison between automated cell counts
      and the mean manual cell counts on 66 DARC images showed significant correlation
      between the two methods (Pearson's correlation coefficient 0.978 (p < 0.001), R
      Squared = 0.956. The Intraclass correlation coefficient was 0.986 (95% CI 0.977
      0.991, p < 0.001), and Cronbach's alpha measure of consistency = 0.986,
      confirming excellent correlation and consistency. No significant difference (p =
      0.922, 95% CI: -5.53 to 6.10) was detected between the cell counts of the two
      methods. CONCLUSIONS: The novel automated algorithm enabled accurate
      quantification of apoptosing RGCs that is highly comparable to manual counting,
      and appears to minimise operator-bias, whilst being both fast and reproducible.
      This may prove to be a valuable method of quantifying apoptosing retinal cells,
      with particular relevance to translation in the clinic, where a Phase I clinical
      trial of DARC in glaucoma patients is due to start shortly.

PMID- 24902593
TI  - Research ethics and case studies in psychology: a commentary on Taus v. Loftus.
AB  - Loftus and Guyer have been criticized for the methods they employed in
      investigating an anonymous case study published by Corwin and Olafson. This
      article examines the ethical dimensions of their investigation. Loftus and Guyer
      have offered three defenses for their actions. All three of those defenses lack
      merit. Their investigation did not constitute oral history because it failed to
      comport with the basic requirements of that practice. Their investigation did not
      constitute ethical journalism because of the unjustified use of anonymous sources
      and the clear violation of basic fairness. Their investigation did not constitute
      justified medical research because of a failure to analyze or weigh the harms
      against the benefits. Their methods also violated ethical principles for
      psychologists, including the rule against activities that could reasonably be
      expected to impair the psychologist's objectivity. This case demonstrates that
      there is no ethical way to investigate a clinical case, without the patient's
      approval, that is both comprehensive enough to provide strong scholarship and yet
      respectful enough of privacy and medical confidentiality to honor important
      professional norms. 

PMID- 24902594
TI  - Published case reports: one woman's account of having her confidentiality
      violated.
AB  - This is a personal story regarding one woman's experience of serving as a case
      study protagonist and later having a psychologist uncover her identity and retell
      her life story in the name of scientific investigative journalism. As a
      participant in a psychological case report, I believed that my confidentiality
      would be protected. Unfortunately, this case study participant found herself in
      the middle of the Memory Wars, and that turned out to be the catalyst for an
      unwanted inquiry into my life. A well-known memory researcher hired a private
      investigator to find me, gained access to a great deal of private information
      about me, and published this in detail without my permission. I discuss in this
      article how these actions affected my life in some very serious ways. I raise
      several issues about the meaning of my experience for further case study authors
      and the clients whose lives they present, as well as questions about the duties
      of psychologists to the subjects of their research and inquiry. 

PMID- 24902595
TI  - Looking beyond prevalence: a demographic profile of survivors of intimate partner
      violence with disabilities.
AB  - The abuse of individuals with disabilities is a widespread problem that has
      received minimal attention in scholarly research on intimate partner violence
      (IPV). As a result, the literature offers neither a general demographic profile
      of IPV survivors with disabilities nor an examination of the relationships
      between IPV and individuals with specific types of disabilities. This article
      addresses these gaps by reporting the results of a retrospective case study
      review of 886 client files, covering an 8-year service period in a non
      residential domestic violence disability program. The study examined key
      demographics along with familial, social, and contextual aspects of IPV among
      women with disabilities, and provides crucial information for service providers
      who must understand the multifaceted and unique needs of survivors. Findings are
      discussed in terms of their relevance to abuse-related outcomes and corresponding
      best practices with this population. 

PMID- 24902596
TI  - Case-control study of risk factors for infectious mastitis in Spanish
      breastfeeding women.
AB  - BACKGROUND: The purpose of this study was to identify potential predisposing
      factors associated with human infectious mastitis. METHODS: We conducted a case
      control study among breastfeeding women, with 368 cases (women with mastitis) and
      148 controls. Data were collected by a questionnaire designed to obtain
      retrospective information about several factors related to medical history of
      mother and infant, different aspects of pregnancy, delivery and postpartum, and
      breastfeeding practices that could be involved in mastitis. Bivariate analyses
      and multivariate logistic regression model were used to examine the relationship
      between mastitis and these factors. RESULTS: The variables significantly- and
      independently-associated with mastitis were cracked nipples (P < 0.0001), oral
      antibiotics during breastfeeding (P < 0.0001), breast pumps (P < 0.0001), topical
      antifungal medication during breastfeeding (P = 0.0009), mastitis in previous
      lactations (P = 0.0014), breast milk coming in later than 24 h postpartum (P =
      0.0016), history of mastitis in the family (P = 0.0028), mother-infant separation
      longer than 24 h (P = 0.0027), cream on nipples (P = 0.0228) and throat infection
      (P = 0.0224). CONCLUSIONS: Valuable factors related to an increased risk of
      infectious mastitis have been identified. This knowledge will allow practitioners
      to provide appropriate management advice about modifiable risk factors, such as
      the use of pumps or inappropriate medication. They also could identify before
      delivery those women at an increased risk of developing mastitis, such as those
      having a familial history of mastitis, and thus develop strategies to prevent
      this condition.

PMID- 24902598
TI  - Life cycle biological efficiency of mice divergently selected for heat loss.
AB  - Divergent selection in mice for heat loss was conducted in 3 independent
      replicates creating a high maintenance, high heat loss (MH) and low maintenance,
      low heat loss (ML) line and unselected control (MC). Improvement in feed
      efficiency was observed in ML mice due to a reduced maintenance energy
      requirement but there was also a slight decline in reproductive performance,
      survivability, and lean content, particularly when compared to MC animals. The
      objective of this study was to model a life cycle scenario similar to a livestock
      production system and calculate total inputs and outputs to estimate overall
      biological efficiency of these lines and determine if reduced feed intake
      resulted in improved life cycle efficiency. Feed intake, reproductive
      performance, growth, and body composition were recorded on 21 mating pairs from
      each line * replicate combination, cohabitated at 7 wk of age and maintained for
      up to 1 yr unless culled. Proportion of animals at each parity was calculated
      from survival rates estimated from previous research when enforcing a maximum of
      4, 8, or 12 allowed parities. This parity distribution was then combined with
      values from previous studies to calculate inputs and outputs of mating pairs and
      offspring produced in a single cycle at equilibrium. Offspring output was defined
      as kilograms of lean output of offspring at 49 d. Offspring input was defined as
      megacalories of energy intake for growing offspring from 21 to 49 d. Parent
      output was defined as kilograms of lean output of culled parents. Parent input
      was defined as megacalories of energy intake for mating pairs from weaning of one
      parity to weaning of the next. Offspring output was greatest in MC mice due to
      superior BW and numbers weaned, while output was lowest in ML mice due to smaller
      litter sizes and lean content. Parent output did not differ substantially between
      lines but was greatest in MH mice due to poorer survival rates resulting in more
      culled animals. Input was greatest in MH and lowest for ML mice for both
      offspring and parent pairs, consistent with previous results in these lines. Life
      cycle efficiency was similar in MC and ML mice, while MH mice were least
      efficient. Ultimately, superior output in MC mice slightly outweighed the lower
      inputs in ML animals resulting from decreased maintenance energy requirements.
      Therefore, selection to reduce maintenance energy requirements may be more useful
      in terminal crosses or in a selection index to reduce possible negative effects
      on output, especially reproductive performance. 

PMID- 24902597
TI  - Phytase properties and locations in tissues of transgenic pigs secreting phytase
      in the saliva.
AB  - A transgenic Cassie (CA) line of Yorkshire (YK) pigs was developed using a
      transgene composed of the mouse parotid secretory protein promoter linked to the
      Escherichia coli phytase gene integrated in chromosome 4. Previous studies
      documented that salivary secretion of phytase was sufficient to enable efficient
      digestion of plant feed phytate P. In the present study the catalytic properties
      and tissue distribution of the phytase in CA pigs were determined by a
      combination of enzymatic assays, immunohistochemistry, and immunoblots of tissue
      samples. The E. coli phytase had a mass of 44.82 kDa whereas the phytase secreted
      in CA saliva had a mass of 52.42 kDa as a result of glycosylation of the enzyme
      in the parotid gland. Despite the difference in size, the 2 enzymes exhibited
      similar substrate specificities, and substrate affinity ( K: m) and maximum
      hydrolytic activity ( V: max) catalytic properties. Phytase assays showed that
      the enzyme was present at high specific activity in the salivary glands with low
      activity in the soft palate and essentially none in the kidney, lean (muscle),
      liver, or skin of CA pigs and none in YK pigs. This conclusion was supported by
      immunoblot analysis using a polyclonal anti-phytase antibody. Immunohistochemical
      analysis of 83 different tissue locations of CA and YK pigs confirmed the
      ubiquitous presence of phytase in serous cells of the salivary glands and the
      localized presence of phytase in both serous and mixed cell types in the
      submucosal glands of the oropharynx; in the pharynx, tonsils, and esophagus; in
      some Bowman's glands in the nasal mucosa and eustachian tube; and in the prostate
      gland of CA boars. Furthermore, it showed the absence of phytase from the kidney,
      lean, liver, and skin of CA pigs. Phytase was not detected in any of the
      conventional YK tissues tested. The phytase was found to be glycosylated with the
      allergenic galactose-alpha-1,3-galactose (alpha-gal) epitope by immunoblotting
      using alpha-gal specific monoclonal antibodies. Galactose-alpha-1,3-galactose
      glycosylation of proteins is a common feature of pork and other red meats. The
      alpha-gal epitope was shown to be associated with a few proteins in muscle and
      skin but with the greatest number of proteins in kidney and parotid tissues of CA
      and YK pigs. The absence of phytase from the major food tissues and the
      displacement of other alpha-gal glycosylated proteins in the parotid glands by
      alpha-gal glycosylated phytase in conjunction with previously published data
      support the contention that expression of the novel phytase has minimal influence
      on pork quality and safety. 

PMID- 24902599
TI  - Maintenance energy requirements of beef cows and relationship with cow and calf
      performance, metabolic hormones, and functional proteins.
AB  - Gestating Angus, nonlactating, spring-calving cows were used to determine
      variation in maintenance energy requirements (MR); to evaluate the relationship
      among MR and cow and calf performance, plasma concentrations of IGF-I, T4,
      glucose, insulin, and ruminal temperature; and to describe the LM proteome and
      evaluate protein abundance in cows with different MR. Cows (4 to 7 yr of age)
      with a BCS of 5.0 +/- 0.2 and BW of 582 +/- 37 kg in the second to third
      trimester of gestation were studied in 3 trials (trial 1, n = 23; trial 2, n =
      32; trial 3, n = 38). Cows were individually fed a complete diet in amounts to
      meet predicted MR (Level 1 Model of NRC), and feed intake was adjusted weekly
      until constant BW was achieved for at least 21 d (maintenance). Cows were
      classified on the basis of MR as low (>0.5 SD less than mean, LMR), moderate (+/
      0.5 SD of mean, MMR), or high (>0.5 SD more than mean, HMR) MR. Blood samples
      were taken at maintenance and at 2 mo postpartum in trial 2. Muscle biopsies were
      taken from LMR and HMR after cows consumed actual MR for 28 d (trial 2) or 21 d
      (trial 3). Proteins from LM were separated by 2-dimensional difference gel
      electrophoresis and were identified, and abundance was quantified and compared.
      The greatest differences in MR between cows were 29%, 24%, and 25% in trials 1,
      2, and 3, respectively. Daily MR (NEm, kcal.BW(-0.75).d(-1)) averaged 89.2 +/-
      6.3, 93.0 +/- 4.9, and 90.4 +/- 4.6 in trials 1, 2, and 3, respectively.
      Postpartum BW and BCS, calf birth and weaning weights, postpartum luteal
      activity, and ruminal temperature were not influenced by MR of the cows.
      Concentrations of IGF-I were greater (P = 0.001) in plasma of MMR compared with
      LMR cows consuming predicted MR diets, and MR was negatively correlated with
      concentrations of IGF-I in plasma (r = -0.38; P = 0.05) at 2 mo postpartum. A
      total of 103 proteins were isolated from LM; 52 gene products were identified.
      Abundance of specific proteins in the LM was not influenced (P > 0.11) by MR.
      Variation in MR of cows will make it possible to improve feed efficiency by
      selection. Identification of biomarkers for MR will allow selection of more
      efficient cows, which consume less feed and produce calves with similar weaning
      weights. Productive cows that require less feed for maintenance will improve
      efficiency of production and enhance sustainability of the environment. 

PMID- 24902600
TI  - Epigenetics as a basis for diagnosis of neurodevelopmental disorders: challenges
      and opportunities.
AB  - Neurodevelopmental disorders, such as autism, are complex entities that can be
      caused by biological and social factors. In a subset of patients with congenital
      neurodevelopmental disorders, clear diagnosis can be achieved using DNA sequence
      based analysis to identify changes in the DNA sequence (genetic variation).
      However, it has recently become clear that changes to the secondary modifications
      of DNA and histone structures (epigenetic variation) can also cause
      neurodevelopmental disorders via alteration of neural gene function. Moreover, it
      has recently been demonstrated that epigenetic modifications are more susceptible
      to alterations induced by environmental factors than are DNA sequences, and that
      some drugs commonly used reverse mental-stress induced alterations to histone
      modifications in neural genes. Therefore, application of diagnostic assays to
      detect epigenetic alterations will provide new insight into the characterization
      and treatment of neurodevelopmental disorders. 

PMID- 24902601
TI  - The fickle nature of similarity change as a result of categorization.
AB  - Several researchers have reported that learning a particular categorization leads
      to compatible changes in the similarity structure of the categorized stimuli. The
      purpose of this study is to examine whether different category structures may
      lead to greater or less corresponding similarity change. We created six category
      structures and examined changes in similarity within categories or between
      categories, as a result of categorization, in between-participant conditions. The
      best supported hypothesis was that the ease of learning a categorization affects
      change in within-categories similarity, so that greater (within-categories)
      similarity change was observed for category structures that were harder to learn.

PMID- 24902602
TI  - Hydrogen-tunneling in biologically relevant small molecules: the rotamerizations
      of alpha-ketocarboxylic acids.
AB  - Quantum mechanical tunneling governs the C-O bond rotamerization of simple alkyl
      and aryl carboxylic acid conformers at cryogenic temperatures. In this study, we
      report tunneling investigations on a series of electronically different alpha
      ketocarboxylic acids including glyoxylic, pyruvic, cyclopropylglyoxylic, and
      phenylglyoxylic acid in solid Ar and Ne as host materials at temperatures ranging
      from 3 to 20 K. The higher-lying rotamers generated through photoirradiation with
      wavelengths of lambda = 313 nm or lambda > 850 nm convert to their low-energy
      conformers through hydrogen-tunneling, as evident from the time evolution of
      their infrared spectra, and the complete suppression of this process by
      deuteration. The conversion rates sensitively depend on the choice of matrix
      material and the tunneling half-lives range from a few hours to several days and
      are higher in Ne than in Ar for glyoxylic, pyruvic, and cyclopropylglyoxylic
      acid. The advent of tunneling in alpha-ketocarboxylic acids dominates their
      conformational preferences and conceivably also the reactivity of biologically
      and pharmacologically relevant acid congeners. 

PMID- 24902603
TI  - Genomic profiling of collaborative cross founder mice infected with respiratory
      viruses reveals novel transcripts and infection-related strain-specific gene and
      isoform expression.
AB  - Genetic variation between diverse mouse species is well-characterized, yet
      existing knowledge of the mouse transcriptome comes largely from one mouse strain
      (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of
      the mouse species. Gene transcription is dynamic and condition-specific;
      therefore, to better understand the mouse transcriptional response to respiratory
      virus infection, we infected the eight founder strains of the Collaborative Cross
      with either influenza A virus or severe acute respiratory syndrome coronavirus
      and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous
      instances of transcripts that were not present in the C57BL/6J reference
      annotation, indicating that a nontrivial proportion of the mouse genome is
      transcribed but poorly annotated. Of these novel transcripts, 2150 could be
      aligned to human or rat genomes, but not to existing mouse genomes, suggesting
      functionally conserved sequences not yet recorded in mouse genomes. We also found
      that respiratory virus infection induced differential expression of 4287 splicing
      junctions, resulting in strain-specific isoform expression. Of these, 59 were
      influenced by strain-specific mutations within 2 base pairs of key intron-exon
      boundaries, suggesting cis-regulated expression. Our results reveal the
      complexity of the transcriptional response to viral infection, previously
      undocumented genomic elements, and extensive diversity in the response across
      mouse strains. These findings identify hitherto unexplored transcriptional
      patterns and undocumented transcripts in genetically diverse mice. Host genetic
      variation drives the complexity and diversity of the host response by eliciting
      starkly different transcriptional profiles in response to a viral infection. 

PMID- 24902604
TI  - Association mapping of germination traits in Arabidopsis thaliana under light and
      nutrient treatments: searching for G*E effects.
AB  - In the natural world, genotype expression is influenced by an organism's
      environment. Identifying and understanding the genes underlying phenotypes in
      different environments is important for making advances in fields ranging from
      evolution to medicine to agriculture. With the availability of genome-wide
      genetic-marker datasets, it is possible to look for genes that interact with the
      environment. Using the model organism, Arabidopsis thaliana, we looked for genes
      underlying phenotypes as well as genotype-by-environment interactions in four
      germination traits under two light and two nutrient conditions. We then performed
      genome-wide association tests to identify candidate genes underlying the observed
      phenotypes and genotype-by-environment interactions. Of the four germination
      traits examined, only two showed significant genotype-by-environment
      interactions. While genome-wide association analyses did not identify any markers
      or genes explicitly linked to genotype-by-environment interactions, we did
      identify a total of 55 markers and 71 genes associated with germination
      differences. Of the 71 genes, four--ZIGA4, PS1, TOR, and TT12--appear to be
      strong candidates for further study of germination variation under different
      environments.

PMID- 24902605
TI  - Construction of a microsatellites-based linkage map for the white grouper
      (Epinephelus aeneus).
AB  - The white grouper (Epinephelus aeneus) is a promising candidate for domestication
      and aquaculture due to its fast growth, excellent taste, and high market price. A
      linkage map is an essential framework for mapping quantitative trait loci for
      economic traits and the study of genome evolution. DNA of a single individual was
      deep-sequenced, and microsatellite markers were identified in 177 of the largest
      scaffolds of the sequence assembly. The success rate of developing polymorphic
      homologous markers was 94.9% compared with 63.1% of heterologous markers from
      other grouper species. Of the 12 adult mature fish present in the broodstock
      tank, two males and two females were identified as parents of the assigned
      offspring by parenthood analysis using 34 heterologous markers. A single full-sib
      family of 48 individuals was established for the construction of first-generation
      linkage maps based on genotyping data of 222 microsatellites. The markers were
      assigned to 24 linkage groups in accordance to the 24 chromosomal pairs. The
      female and male maps consisting of 203 and 202 markers spanned 1053 and 886 cM,
      with an average intermarker distance of 5.8 and 5.0 cM, respectively. Mapping of
      markers to linkage groups ends was enriched by using markers originating from
      scaffolds harboring telomeric repeat-containing RNA. Comparative mapping showed
      high synteny relationships among the white grouper, kelp grouper (E. bruneus),
      orange-spotted grouper (E. coioides), and Nile tilapia (Oreochromis niloticus).
      Thus, it would be useful to integrate the markers that were developed for
      different groupers, depending on sharing of sequence data, into a comprehensive
      consensus map. 

PMID- 24902606
TI  - Genetic interactions between P elements involved in piRNA-mediated repression of
      hybrid dysgenesis in Drosophila melanogaster.
AB  - Previous studies have shown that telomeric P elements inserted at the left end of
      the X chromosome are anchors of the P cytotype, the maternally inherited state
      that regulates P-element activity in the germ line of Drosophila melanogaster.
      This regulation is mediated by small RNAs that associate with the Piwi family of
      proteins (piRNAs). We extend the analysis of cytotype regulation by studying new
      combinations of telomeric and nontelomeric P elements (TPs and non-TPs). TPs
      interact with each other to enhance cytotype regulation. This synergism involves
      a strictly maternal effect, called presetting, which is apparently mediated by
      piRNAs transmitted through the egg. Presetting by a maternal TP can elicit
      regulation by an inactive paternally inherited TP, possibly by stimulating its
      production of primary piRNAs. When one TP has come from a stock heterozygous for
      a mutation in the aubergine, piwi, or Suppressor of variegation 205 genes, the
      synergism between two TPs is impaired. TPs also interact with non-TPs to enhance
      cytotype regulation, even though the non-TPs lack regulatory ability on their
      own. Non-TPs are not susceptible to presetting by a TP, nor is a TP susceptible
      to presetting by a non-TP. The synergism between TPs and non-TPs is stronger when
      the TP was inherited maternally. This synergism may be due to the accumulation of
      secondary piRNAs created by ping-pong cycling between primary piRNAs from the TPs
      and mRNAs from the non-TPs. Maternal transmission of P-element piRNAs plays an
      important role in the maintenance of strong cytotype regulation over generations.

PMID- 24902608
TI  - Lennox-Gastaut syndrome and phenotype: secondary network epilepsies.
AB  - OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe epilepsy phenotype with
      characteristic electroclinical features despite diverse etiologies. We previously
      found common cerebral networks involved during slow spike-and-wave (SSW) and
      generalized paroxysmal fast activity (PFA), characteristic interictal discharges.
      Some patients have a Lennox-Gastaut-like phenotype and cortical lesions. We
      wished to explore the interaction between cerebral networks and lesions in this
      group. METHODS: 3 Tesla electroencephalography-functional magnetic resonance
      imaging (EEG-fMRI) on six subjects with Lennox-Gastaut phenotype and a structural
      lesion. Timings of SSW and PFA events were used in an event-related fMRI
      analysis, and to estimate the time course of the hemodynamic response from key
      regions. RESULTS: (1) PFA-robust fMRI signal increases were observed in frontal
      and parietal association cortical areas, thalamus, and pons, with simultaneous
      increases in both "attention" and resting-state (default mode) networks, a highly
      unusual pattern. (2) SSW showed mixed increased and decreased fMRI activity, with
      preevent increases in association cortex and thalamus, and then prominent
      postevent reduction. There was decreased fMRI activity in primary cortical areas.
      (3) Lesion-variable fMRI increases were observed during PFA and SSW discharges.
      Three subjects who proceeded to lesionectomy are >1 year seizure-free.
      SIGNIFICANCE: We conceptualize Lennox-Gastaut phenotype as a being a network
      epilepsy, where key cerebral networks become autonomously unstable. Epileptiform
      activity in Lennox-Gastaut phenotype, and by implication in LGS, appears to be
      amplified and expressed through association cortical areas, possibly because the
      attention and default-mode networks are widely interconnected, fundamental brain
      networks. Seizure freedom in the subjects who proceeded to lesionectomy suggests
      that cortical lesions are able to establish and maintain this abnormal unstable
      network behavior. LGS may be considered a secondary network epilepsy because the
      unifying epileptic manifestations of the disorder, including PFA and SSW, reflect
      network dysfunction, rather than the specific initiating process.

PMID- 24902609
TI  - Clinical impact of body mass index on bactibilia and bacteremia.
AB  - BACKGROUND: The aim of this study was to evaluate the association between obesity
      and infected bile or bacteremia in patients with acute calculous cholecystitis.
      METHODS: Authors analyzed the medical records of 139 patients who had undergone
      cholecystectomy for the treatment of acute calculous cholecystitis from January
      2007 to June 2013 in a single teaching hospital. Association of body mass index
      (BMI) with bactibilia and bacteremia was assessed using univariate and
      multivariate analysis. Clinical findings and biliary infection related data were
      recorded for the following variables: gender, age, alcohol and smoking history,
      the results of blood and bile cultures, cholesterolosis, diabetes, hypertension,
      and duration of the hospital stay. RESULTS: The microbial culture rate of
      bactibilia and bacteremia were 50.4% and 21.6%, respectively. In the univariate
      analysis, bacteremia was associated with bactibilia (OR: 4.33, p = 0.002). In the
      multivariate analysis for the risk factors of bactibilia, BMI and bacteremia were
      related with bactibilia (OR: 0.59, 95% CI: 0.42-0.84, p = 0.003) (OR: 3.32, 95%
      CI: 1.22-9, p = 0.02). In the multivariate analysis for the risk factors of
      bacteremia, BMI, bactibilia and age were related with bacteremia (OR: 0.76, 95%
      CI: 0.59-0.99, p = 0.04) (OR: 3.46, 95% CI: 1.27-9.45, p = 0.02) (OR: 1.05, 95%
      CI: 1.01-1.09, p = 0.02). CONCLUSION: In this retrospective study, BMI was
      inversely correlated with bacteremia or bactibilia, which means obese or
      overweight patients are less likely to be associated with bacteremia or
      bactibilia in patients with acute calculous cholecystitis.

PMID- 24902610
TI  - Clostridium difficile infection in liver transplant recipients: a retrospective
      study of rates, risk factors and outcomes.
AB  - Clostridium difficile infection (CDI) occurs in 3-7% of liver transplant
      recipients (LTR). However, few data exist on the recent epidemiology, predictors
      and outcomes of CDI in LTR. A cohort study was performed including LTR from 2000
      to 2010 at a tertiary care hospital in Detroit. CDI was defined as diarrhea with
      a stool C. difficile positive test. Data analyzed included demographics,
      comorbidities, length of stay (LOS), severity of CDI, rates of recurrence (<12
      weeks), relapse (<4 weeks) and overall mortality. Predictors of CDI were
      calculated using Cox proportional hazard model; 970 LTR were followed for years.
      Overall prevalence of CDI was 18.9%. Incidence of CDI within 1 year of transplant
      was 12.4%. Severe CDI occurred in 29.1%. CDI recurrence and relapse rates were
      16.9% and 9.7%, respectively. Independent predictors of CDI were year of
      transplant (hazard ratio [HR] 1.137, 95% confidence interval [CI] 1.06-1.22; p <
      0.001), white race (105/162 whites, HR 1.47, 95% CI 1.03-2.1; p = 0.035), Model
      for End-Stage Liver Disease score (HR 1.03, 95% CI 1.01-1.045, p = 0.003) and LOS
      (HR 1.01, 95% CI 1.005-1.02, p < 0.001). Significant mortality was observed among
      LTR with CDI compared to those without CDI (p = 0.003). We concluded that CDI is
      common among LTR and is associated with higher mortality. 

PMID- 24902607
TI  - Pharmacological regulators of autophagy and their link with modulators of lupus
      disease.
AB  - Autophagy is a central regulator of cell survival. It displays both anti- and pro
      death roles that are decisive in the maintenance of cell homeostasis. Initially
      described in several eukaryotic cellular models as being induced under nutrient
      stress favouring survival by energy supply, autophagy was found later to display
      other decisive physiological roles, especially in the immune system. Thus, it is
      involved in antigen presentation and lymphocyte differentiation as well as in the
      balance regulating survival/death and activation of lymphocytes. Autophagy
      therefore appears to be central in the regulation of inflammation. The
      observation that autophagy is deregulated in systemic lupus erythematosus is
      recent. This discovery revives the programme dealing with the design and
      development of pharmacological autophagy regulators in the therapeutic context of
      lupus, a debilitating autoimmune disease that affects several million people in
      the world. A large number of molecules that positively and negatively regulate
      autophagy have been described, most of them with therapeutic indications in
      cancer and infection. Only a few, however, are effectively potent activators or
      inhibitors endowed with experimentally demonstrated selective properties. In this
      review article, we highlight the most relevant ones and summarize what we know
      regarding their mechanism of action. We emphasize the link between
      pharmacological regulators of autophagy and inducers or inhibitors of lupus
      disease and discuss the fundamental and pharmacological/therapeutic interest of
      this functional interplay. 

PMID- 24902611
TI  - Swept-source optical coherence tomography imaging in conservative and surgical
      management of premacular haemorrhages showing inflammatory response.

PMID- 24902612
TI  - Calcitonin gene-related peptide and vascular endothelial growth factor are
      expressed in lesional but not uninvolved skin in chronic spontaneous urticaria.
AB  - BACKGROUND: The mechanisms for producing weals in chronic spontaneous
      (idiopathic) urticaria (CSU) are incompletely understood. Leucocyte infiltration
      with vascular leakage and expression of the potent vasoactive agents' calcitonin
      gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF) are
      features of late-phase allergic skin reactions, previously proposed as a model of
      CSU. OBJECTIVE: To measure CGRP and VEGF expression in lesional and non-lesional
      skin from CSU patients and to compare results with a control group. METHODS:
      Eight paired biopsies (one from 4-8 h spontaneous weals and one from uninvolved
      skin) were taken from eight patients with CSU and nine control subjects and
      studied by immunohistochemistry and confocal microscopy. RESULTS: Lesional skin
      in CSU contained significantly more CGRP+ and VEGF+ cells than non-lesional skin.
      No significant differences were observed in CGRP and VEGF expression between non
      lesional skin and controls. In lesional skin, VEGF and CGRP co-localised to UEA
      1+ blood vessels. CGRP was also expressed by neutrophils and eosinophils and to a
      lesser extent by CD90(+) fibroblasts, mast cells, CD3(+) and CD68(+) cells. CGRP
      and VEGF expression was not related to the duration of disease. CONCLUSION AND
      CLINICAL RELEVANCE: Increased expression of CGRP and VEGF in lesional, but not
      uninvolved, skin indicates that these potent vasoactive agents may play a role in
      wealing and tissue oedema in CSU so representing novel targets in therapy.

PMID- 24902613
TI  - Frontal and thalamic changes of GABA concentration indicate dysfunction of
      thalamofrontal networks in juvenile myoclonic epilepsy.
AB  - OBJECTIVE: Juvenile myoclonic epilepsy (JME) has been considered to be a frontal
      variant of thalamocortical network dysfunction in epilepsy. Changes of gamma
      aminobutyric acid (GABA)ergic neurotransmission may play a key role in this
      dysfunction. Magnetic resonance spectroscopy (MRS) is the only noninvasive method
      to measure GABA concentrations in different brain regions. We measured GABA and
      other metabolite concentrations in the thalamus and frontal lobe of patients with
      JME. METHODS: A specific protocol was used for determining GABA concentrations in
      the thalamus, frontal lobe, and motor cortex contralateral to the handedness in
      15 patients with JME and 15 age-matched controls. In addition, we measured
      concentrations of glutamate and glutamine, N-acetyl-aspartate (NAA), myoinositol,
      creatine, and choline using MRS with short echo time. JME-related concentration
      changes were analyzed comparing patients to controls, also considering potential
      effects of antiepileptic drugs. RESULTS: In patients with JME, GABA and NAA were
      reduced in the thalamus (p = 0.03 and p = 0.02), whereas frontal GABA and
      glutamine were elevated (p = 0.046 and p = 0.03). MRS revealed reduced NAA in the
      thalamic gray matter contralateral to the handedness (p = 0.04 each). These
      changes were found consistently in patients treated with new antiepileptic drugs
      and with valproate, although the extent of metabolic changes differed between
      these treatments. SIGNIFICANCE: Decreased thalamic and increased frontal GABA
      suggest a dysfunction of GABAergic neurotransmission in these brain regions of
      patients with JME. The NAA decrease in the gray matter of the thalamus may hint
      to a damage of GABAergic neurons, whereas frontal increase of GABA and its
      precursor glutamine may reflect increased density in GABAergic neurons due to
      subtle cortical disorganization in the thalamofrontal network.

PMID- 24902614
TI  - Predicting biochemical response to clomiphene citrate in men with hypogonadism.
AB  - INTRODUCTION: Clomiphene citrate (CC) is as an effective treatment for men with
      hypogonadism (HG). Identifying the ideal candidate for this strategy has to date
      largely relied upon a patient's interest in preservation of testicular volume and
      spermatogenesis. AIM: This analysis was undertaken to define if predictors
      existed of robust elevation in serum testosterone (T) levels in response to CC.
      METHODS: Seventy-six men with a diagnosis of HG (two separate early morning total
      T levels <300 ng/dL) opting for CC therapy constituted the study population.
      Demographic, comorbidity data, and physical and laboratory characteristics were
      recorded. Laboratory tests were conducted 4 weeks after commencement and every 6
      months thereafter. Multivariable analysis was conducted to define if predictors
      of biochemical response could be identified. Parameters included in the model
      were patient age, mean testicular volume, varicocele presence, and baseline total
      T, free T, and luteinizing hormone (LH) levels. MAIN OUTCOME MEASURE: Successful
      biochemical response to CC, defined as an increase of >=200 ng/dL in total T
      level at >=6 months after commencing CC, was the main outcome measure. RESULTS:
      Mean age was 46 +/- 22 years. Mean pretreatment testicular volume was 16 +/- 8
      mL. Mean baseline T and LH levels were 179 +/- 72 ng/dL and 7.2 +/- 5.6 IU/mL,
      respectively. Mean total T on CC was 467 +/- 190 ng/dL. Forty-seven patients
      (62%) met the responder definition, with a mean increase in total T levels of 302
      +/- 76 (204-464) ng/dL. In CC responders, the mean LH rise was 5.6 +/- 3.1 IU/mL.
      On multivariable analysis, factors predictive of CC response included: mean
      testicular volume (adjusted [adj.] r = 0.32, P < 0.01), mean testicular volume
      >=14 mL (hazard ratio [HR] 2.2, P < 0.01), LH level (adj. r = 0.48, P < 0.001),
      and LH level <=6 IU/mL (HR 3.5, P < 0.001). CONCLUSION: These data indicate that
      two thirds of men with HG meet a robust responder definition and that
      pretreatment testicular volume and LH levels (in continuous and dichotomized
      fashions) are predictors of response.

PMID- 24902615
TI  - Core/shell quantum dot based luminescent solar concentrators with reduced
      reabsorption and enhanced efficiency.
AB  - CdSe/CdS core/shell quantum dots (QDs) have been optimized toward luminescent
      solar concentration (LSC) applications. Systematically increasing the shell
      thickness continuously reduced reabsorption up to a factor of 45 for the thickest
      QDs studied (with ca. 14 monolayers of CdS) compared to the initial CdSe cores.
      Moreover, an improved synthetic method was developed that retains a high
      fluorescence quantum yield, even for particles with the thickest shell volume,
      for which a quantum yield of 86% was measured in solution. These high quantum
      yield thick shell quantum dots were embedded in a polymer matrix, yielding highly
      transparent composites to serve as prototype LSCs, which exhibited an optical
      efficiency as high as 48%. A Monte Carlo simulation was developed to model LSC
      performance and to identify the major loss channels for LSCs incorporating the
      materials developed. The results of the simulation are in excellent agreement
      with the experimental data. 

PMID- 24902616
TI  - Cancer incidence among patients with a hospital diagnosis of pruritus: a
      nationwide Danish cohort study.
AB  - BACKGROUND: Pruritus is a frequent complaint in patients with cancer. However, no
      large study has examined pruritus as a marker of undiagnosed cancer. OBJECTIVES:
      To examine the association between inpatient, outpatient and emergency hospital
      diagnoses of pruritus and subsequent cancer diagnoses. METHODS: In this
      nationwide Danish cohort study, we used medical databases to identify all
      patients (n = 12,813) with a diagnosis of pruritus during the period 1978-2011
      and followed them until a first-time cancer diagnosis, emigration, death or 31
      December 2011. We computed standardized incidence ratios (SIRs) for cancer as the
      observed to expected number of cancers based on national cancer incidence rates.
      We calculated the 1-year absolute risk of cancer, treating death as a competing
      risk. RESULTS: The overall SIR of cancer was 1.13 [95% confidence interval (CI)
      1.07-1.20]: 1.22 (95% CI 1.13-1.33) among men and 1.05 (95% CI 0.97-1.14) among
      women. The SIR was 1.20 (95% CI 1.08-1.33) among patients with a previous
      diagnosis of dermatological disease and 1.10 (95% CI 1.02-1.18) among patients
      without such a diagnosis. Both haematological and various solid cancers were
      observed at increased rates. Overall, the highest SIRs were observed during the
      first 3 months of follow-up, declining rapidly thereafter. The 1-year absolute
      risk of a cancer diagnosis was 1.63% and 155 patients with pruritus would have
      needed to be examined to detect one excess cancer. CONCLUSIONS: Pruritus may be a
      marker of occult cancer. Further studies are needed to assess the prognostic
      benefit of screening for cancer in patients with pruritus.

PMID- 24902617
TI  - Broader autism phenotype in mothers predicts social responsiveness in young
      children with autism spectrum disorders.
AB  - AIMS: The aim of this study was to identify phenotypes in mothers and fathers
      that are specifically associated with disturbances in reciprocal social
      interactions and communication in their young children with autism spectrum
      disorder (ASD) in a Japanese sample. METHODS: Autistic traits in parents were
      evaluated using the Autism-spectrum Quotient (AQ), the Empathy Quotient (EQ) and
      the Systemizing Quotient (SQ) in 88 parents (44 mothers and corresponding
      fathers) of children with ASD and in 60 parents (30 mothers and corresponding
      fathers) of typically developing (TD) children. For the measurement of autistic
      traits in children, we employed the Social Responsiveness Scale (SRS). RESULTS:
      In two of the five AQ subscales (social skills and communication), the parents of
      ASD children scored significantly higher than did the parents of TD children,
      regardless of whether the parent was a mother or a father. In addition, in
      mothers of ASD children, there were significant positive correlations between two
      of the five AQ subscales (attention-switching and communication) and the SRS T
      score in their children. CONCLUSIONS: This is the first study to demonstrate that
      the social skills and communication subscales in the AQ are more sensitive as
      autism traits in a Japanese sample and to demonstrate that some autistic traits
      in mothers are specifically associated with disturbances in the social ability of
      their young children with ASD, as measured by the SRS score. Further study is
      necessary to determine whether these results were caused by genetic or
      environmental factors.

PMID- 24902620
TI  - Outdoor fungi and child asthma health service attendances.
AB  - Asthma is a significant global public health issue. Severe asthma exacerbations
      can be triggered by environmental factors and require medical care from health
      services. Although it is known that fungal exposure may lead to allergic
      sensitization, little is understood about its impact on asthma exacerbations.
      This review aims to examine whether outdoor fungi play a significant role in
      child asthma exacerbations. Systematic search of seven electronic databases and
      hand searching for peer-reviewed studies published in English, up to 31 August
      2013. Inclusion criteria were study population aged <18 yr, diagnosis of asthma,
      attended a health service; outdoor fungi exposure was reported. Quality and risk
      of bias assessments were conducted. Due to significant heterogeneity, meta
      analysis was not conducted. Of the 1896 articles found, 15 were eligible.
      Findings were not consistent, possibly due to methodological variations in
      exposure classifications, statistical methods and inclusion of confounders. Cross
      sectional studies found no or weak associations. All but one time series studies
      indicated an association that varied between fungal species. Increasing evidence
      indicates that asthmatic children are susceptible to asthma exacerbations when
      exposed to outdoor fungal spores. There is limited understanding of the
      contributions of different fungal species. Research is needed to investigate
      interactions of outdoor fungi with pollen, air pollutants and respiratory
      viruses. 

PMID- 24902619
TI  - In utero sensitization modulates IgG isotype, IFN-gamma and IL-10 responses of
      neonates in bancroftian filariasis.
AB  - In utero exposure has been considered as a risk factor for filarial infection. To
      evaluate the influence of maternal infection on filarial-specific IgG subclass
      response in neonates and their correlation with plasma levels IL-10 and
      interferon-gamma, 145 pairs of mothers and their respective cord bloods were
      examined. Transplacental transfer of circulating filarial antigen (CFA) was
      observed in 34.8% cord bloods from CFA positive mothers. Filarial-specific IgG1,
      IgG2 and IgG4 responses of cord bloods were found to be positively correlated
      with CFA of mothers. In contrast, IgG3 responses negatively correlated with CFA
      of mothers. The % of similarity of recognition pattern in the cord blood with
      maternal blood was high for IgG3 response than IgG4 in all three groups. An
      increased levels of IL-10 and decreased levels of interferon gamma (IFN-gamma)
      were observed in cord blood of infected mothers. Interferon gamma was positively
      correlated with IgG3 and negatively correlated with IgG4 level. On the other
      hand, IL-10 was positively correlated with IgG4 and CFA, indicating that
      cytokines may play a role in modulating the immune responses in cord bloods of
      sensitized foetus. The findings of the study reveal that in utero tolerance or
      sensitization may influence the filarial-specific immunity to infection in
      neonates.

PMID- 24902621
TI  - Deletion polymorphism of GSTT1 gene as protective marker for allergic rhinitis.
AB  - BACKGROUND AND AIMS: Allergic rhinitis (AR) is one of the most common respiratory
      diseases among human populations. Strong evidence suggests that genetic
      predisposition and environmental factors could contribute to the development of
      this complex disease. Glutathione S-transferases (GSTs) are biomarkers of
      inflammation and oxidative stress. These phase II enzymes play a significant role
      in detoxifying xenobiotic compounds. To analyze the role of GST gene
      polymorphisms in AR pathogenesis in a case-control population of 103 patients
      affected by AR and 200 healthy non-allergic subjects. METHODS: We screened
      genomic DNA extracted from buccal cells for GSTM1 positive/null, GSTP1*I105V
      (rs1695) and GSTT1 positive/null polymorphisms. The X(2) -test, odds ratio (OR)
      and logistic regression were used as statistical analyses. RESULTS: Significant
      differences in null genotype distribution between AR patients (13%) and healthy
      controls (30%) were found for the GSTT1 null genotype (OR = 0.30, 95% confidence
      interval = 0.14-0.65; P = 0.001). GSTM1 and GSTP1 polymorphisms did not show any
      significant results. CONCLUSION: Our data indicated that GSTT1 may be a
      susceptibility locus for AR. Specifically, the positive/null polymorphism of
      GSTT1 may be involved in an oxidative stress-related mechanism that may enhance
      pathogenic pathways related to AR. Moreover, beside GSTT1, this deletion
      polymorphism affects also another gene potentially related to AR phenotype,
      LOC391322. This gene belongs to MIF (macrophage migration inhibitory factor) gene
      family and several studies indicated the role of this gene in several immunology
      related phenotypes. Therefore, two different scenarios may explain the observed
      genetic association.

PMID- 24902622
TI  - A confirmatory bifactor analysis of the Hospital Anxiety and Depression Scale in
      an Italian community sample.
AB  - BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is a widely used
      self-report measure to assess emotional distress in clinical populations. As
      highlighted in recent review studies, the latent structure of the HADS is still
      an issue. The aim of this study was to analyze the factorial structure of the
      HADS in a large community sample in Italy, and to test the invariance of the best
      fitting model across age and gender groups. METHODS: Data analyses were carried
      out on a sample of 1.599 participants proportionally stratified according to the
      Italian census population pyramid. Participants aged 18 to 85 years (females =
      51.8%), living in eight different regions of Italy, voluntarily participated in
      the study. The survey questionnaire contained the HADS, Health Status questions,
      and sociodemographic variables. RESULTS: Confirmatory factor analysis indicated
      that a bifactor model, with a general psychological distress factor and two
      orthogonal group factors with anxiety and depression, was the best fitting one
      compared to six alternative factor structures reported in the literature, with
      overall good fit indices [Non-normed Fit Index (NNFI) = .97; Comparative Fit
      Index (CFI) = .98; Root Mean-Square Error of Approximation (RMSEA) = .04]. Multi
      group analyses supported total invariance of the HADS measurement model for males
      and females, and for younger (i.e., 18-44 years old) and older (i.e., 45-85 years
      old) participants. Our descriptive analyses showed that females reported
      significant higher anxiety and general distress mean scores than males. Moreover,
      older participants reported significant higher HADS, anxiety and depression
      scores than younger participants. CONCLUSIONS: The results of the present study
      confirmed that the HADS has good psychometric properties in an Italian community
      sample, and that the HADS scores, especially the general psychological distress
      one, can be reliably used for assessing age and gender differences. In keeping
      with the most recent factorial studies, our analysis supported the superior fit
      of a bifactor model. However, the high factor loadings on the general factor also
      recommend caution in the use of the two subscales as independent measures.

PMID- 24902623
TI  - A mismatch of meaning and intentionality between analyst and analysand.
AB  - In this paper, I will consider a type of misunderstanding in the analytical
      dialogue and the possible unconscious motivations underlying this. I will also
      make reference to the patient's use of the analyst's words for the purpose of
      narcissistic enactment and will explore the extent of the analyst's involvement
      in this. The subjects of misunderstanding and narcissistic enactment will be
      dealt with in relation to a patient's way of processing certain interpretations
      at the beginning of analysis and the concealment of her way of processing the
      analyst's words. By contributing dreams and other significant material in the
      sessions, the patient gradually revealed her phantasies which enabled the analyst
      to uncover the possible factors which determined her particular attribution of
      meaning to the analyst's words and her retention of information about how she had
      initially construed his interpretations.

PMID- 24902624
TI  - Distal-selective hydroformylation using scaffolding catalysis.
AB  - In hydroformylation, phosphorus-based directing groups have been consistently
      successful at placing the aldehyde on the carbon proximal to the directing group.
      The design and synthesis of a novel catalytic directing group are reported that
      promotes aldehyde formation on the carbon distal relative to the directing
      functionality. This scaffolding ligand, which operates through a reversible
      covalent bond to the substrate, has been applied to the diastereoselective
      hydroformylation of homoallylic alcohols to afford delta-lactones selectively.
      Altering the distance between the alcohol and the olefin revealed that
      homoallylic alcohols gives the distal lactone with the highest levels of
      regioselectivity. 

PMID- 24902625
TI  - Clinical impact of the extent of lymph node micrometastasis in undifferentiated
      type early gastric cancer.
AB  - OBJECTIVE: Lymph node (LN) metastasis is one of the most important prognostic
      factors for undifferentiated-type early gastric cancer (EGC). The aim of this
      study was to examine expansion of micrometastasis in regional LNs to clarify the
      importance of lymphadenectomy for undifferentiated-type EGC. METHODS:
      Clinicopathological features of 307 patients with undifferentiated-type EGC who
      underwent gastrectomy with lymphadenectomy between 1997 and 2010 at the
      Department of Surgical Oncology, Osaka City University, were retrospectively
      reviewed. Micrometastasis in LNs was detected by immunohistochemistry using
      anticytokeratin antibody. RESULTS: The incidence of LN metastasis was 1.8% in
      patients with mucosal (pT1a) tumors and 17.3% in those with submucosal (pT1b)
      tumors. Multivariate analysis revealed that lymphatic invasion and tumor depth
      were independently related to LN metastasis. Micrometastasis was found in 41
      (13.3%) patients. Twenty-two patients with pN0 had micrometastasis in the
      perigastric region. Micrometastasis had spread to the area along the left gastric
      or common hepatic artery in 12 patients. Patients with an upgraded stage by
      micrometastasis had significantly worse disease-free survival. CONCLUSIONS: LN
      micrometastasis was observed beyond the perigastric LNs and correlated with poor
      outcomes in patients with undifferentiated-type EGC. These data underscore the
      importance of adequate lymphadenectomy for patients with undifferentiated-type
      EGC. (c) 2014 S. Karger AG, Basel.

PMID- 24902626
TI  - Resorption of PDLLA plates as a nidus for recurrent langerhans cell
      histiocytosis.
AB  - Resorbable plating systems have been adapted into routine use for craniofacial
      reconstruction in children. After implantation in some patients, the area around
      the plates can develop palpable and visible fibrous capsules, with underlying
      bone resorption and a significant foreign-body giant cell reaction. The reaction
      is usually self-limited. We report a case in which Langerhans cell histiocytosis
      was resected, and then recurred at the sites of resorbing plate and screw
      placement in association with a foreign-body giant cell reaction.

PMID- 24902627
TI  - Requirements of a new communication technology for handover and the escalation of
      patient care: a multi-stakeholder analysis.
AB  - RATIONALE, AIMS AND OBJECTIVES: In order to enable safe and efficient information
      transfer between health care professionals during clinical handover and
      escalation of care, existing communication technologies must be updated. This
      study aimed to provide a user-informed guide for the development of an
      application-based communication system (ABCS), tailored for use in patient
      handover and escalation of care. METHODS: Current methods of inter-professional
      communication in health care along with information system needs for
      communication technology were identified through literature review. A focus group
      study was then conducted according to a topic guide developed by health
      innovation and safety researchers. Fifteen doctors and 11 nurses from three
      London hospitals participated in a mixture of homogeneous and heterogeneous
      sessions. The sessions were recorded and transcribed verbatim before being
      subjected to thematic analysis. RESULTS: Seventeen information system needs were
      identified from the literature review. Participants identified six themes
      detailing user perceptions of current communication technology, attitudes to
      smartphone technology and anticipated requirements of an application produced for
      handover and escalation of care. Participants were in favour of an ABCS over
      current methods and expressed enthusiasm for a system with integrated patient
      information and group-messaging functions. CONCLUSION: Despite concerns regarding
      confidentiality and information governance a robust guide for development and
      implementation of an ABCS was produced, taking input from multiple stakeholders
      into account. Handover and escalation of care are vital processes for patient
      safety and communication within these must be optimized. An ABCS for health care
      professionals would be a welcome innovation and may lead to improvements in
      patient safety.

PMID- 24902628
TI  - Sexual satisfaction of infertile couples assessed using the Golombok-Rust
      Inventory of Sexual Satisfaction (GRISS).
AB  - Recently, infertility treatment-related psychological effects are receiving
      increased attention. However, whether sexual satisfaction is reduced amongst
      infertile couples remains to be elucidated. In this study, sexual satisfaction of
      Japanese infertile couples was assessed using a validated questionnaire designed
      to assess the male and female partner individually, and the couple as a whole for
      the first time. This study randomly included 170 infertile couples seen at the
      outpatient clinic and 170 couples that had recently achieved spontaneous
      pregnancy. All couples were given the Japanese version of the Golombok-Rust
      Inventory of Sexual Satisfaction (GRISS). In couples aged 35 years or older, the
      male partners showed significantly worse sexual satisfaction scores than the
      female partners. Sexual satisfaction also deteriorated with therapeutic
      interventions, with mental factors affected more than physical factors.
      Therapeutic interventions such as timed sexual intercourse and assisted
      reproductive technology were considered emotionally stressful for infertile
      couples, with sexual satisfaction accordingly lower in this group than in couples
      achieving spontaneous pregnancy. GRISS successfully evaluated lower sexual
      satisfaction associated with infertility, and hence is a useful tool for
      identifying couples whose sexual satisfaction could be enhanced by counselling or
      other stress-reduction modalities. 

PMID- 24902629
TI  - New inhaler devices - the good, the bad and the ugly.
AB  - Drug delivery to the lungs is an effective way of targeting inhaled therapeutic
      aerosols and treating obstructive airway diseases, such as asthma and chronic
      obstructive pulmonary disease (COPD). In the past 10 years, several new drugs for
      the management of asthma and COPD have been marketed and more are under
      development. These new therapeutic respiratory drugs have been furthered by
      innovations in all categories of pulmonary drug delivery systems to ensure
      optimal aerosolisation performance, consistency in efficacy and satisfactory
      patient adherence. In this review, we discuss the technological advances and
      innovations in recent inhaler devices and the evolving roles of pressurised
      metered-dose inhalers, dry powder inhalers and nebulisers, as well as their
      impact on patient adherence to treatment.

PMID- 24902632
TI  - Late-acting self-incompatibility--the pariah breeding system in flowering plants.
AB  - It is estimated that around half of all species of flowering plants show self
      incompatibility (SI). However, the great majority of species alleged to have SI
      simply comply with 'the inability of a fully fertile hermaphrodite plant to
      produce zygotes when self-pollinated'--a definition that is neutral as to cause.
      Surprisingly few species have been investigated experimentally to determine
      whether their SI has the type of genetic control found in one of the three
      established mechanisms, that is, homomorphic gametophytic, homomorphic
      sporophytic or heteromorphic SI. Furthermore, our knowledge of the molecular
      basis of homomorphic SI derives from a few species in just five families--a small
      sample that has nevertheless revealed the existence of three different molecular
      mechanisms. Importantly, a sizeable cohort of species are self-sterile despite
      the fact that self-pollen tubes reach the ovary and in most cases penetrate
      ovules, a phenomenon called late-acting self-incompatibility (LSI). This review
      draws attention to the confusion between species that show 'self-incompatibility'
      and those that possess one of the 'conventional SI mechanisms' and to argue the
      case for recognition of LSI as having a widespread occurrence and as a mechanism
      that inhibits selfing and promotes outbreeding in many plant species.

PMID- 24902631
TI  - Formant and voice source properties in two male Kunqu Opera roles: a pilot study.
AB  - OBJECTIVE: This investigation analyzes flow glottogram and electroglottogram
      (EGG) parameters as well as the relationship between formant frequencies and
      partials in two male Kunqu Opera roles, Colorful face (CF) and Old man (OM).
      PARTICIPANTS AND METHODS: Four male professional Kunqu Opera singers volunteered
      as participants, 2 singers for each role. Using inverse filtering of the audio
      signal flow glottogram parameters and formant frequencies were measured in each
      note of scales. Two EGG parameters, contact quotient (CoQ) and speed quotient,
      were measured. RESULTS: Formant tuning was observed only in 1 of the OM singers
      and appeared in a pitch range lower than the passaggio range of Western male
      opera singers. Both the CF and the OM role singers showed high CoQ values and low
      values of the normalized amplitude quotient in singing. For 3 of the 4 singers
      CoQ and the level difference between the first and second partials showed a
      positive and a negative correlation with fundamental frequency (F0),
      respectively. CONCLUSIONS: Formant tuning may be applied by a singer of the OM
      role, and both CF and OM role singers may use a rather pressed type of phonation,
      CF singers more than OM singers in the lower part of the pitch range. Most
      singers increased glottal adduction with rising F0.

PMID- 24902633
TI  - Oxidative etching for controlled synthesis of metal nanocrystals: atomic addition
      and subtraction.
AB  - Since the discovery of the role of oxidative etching in shape-controlled metal
      nanostructure synthesis in 2004, it has become a versatile tool to precisely
      manipulate the nucleation and growth of metal nanocrystals at the atomic level.
      Subsequent research has shown that oxidative etching can be used to reshape
      nanocrystals via atomic addition and subtraction. This research has attracted
      extensive attention from the community because of its promising practical
      applications and theoretical value, and as a result, tremendous efforts from
      numerous research groups have been made to expand and apply this method to their
      own research. In this review, we first outline the merits of oxidative etching
      for the controlled synthesis of metal nanocrystals. We then summarize recent
      progress in the use of oxidative etching to control the morphology of a
      nanostructure during and after its synthesis, and analyze its specific functions
      in controlling a variety of nanocrystal parameters. Applications enabled by
      oxidative etching are also briefly presented to show its practical impact.
      Finally, we discuss the challenges and opportunities for further development of
      oxidative etching in nanocrystals synthesis. 

PMID- 24902634
TI  - Graphene as a photothermal switch for controlled drug release.
AB  - Graphene has recently emerged as a novel material in the biomedical field owing
      to its optical properties, biocompatibility, large specific surface area and low
      cost. In this paper, we provide the first demonstration of the possibility of
      using light to remotely trigger the release of drugs from graphene in a highly
      controlled manner. Different drugs including chemotherapeutics and proteins are
      firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a
      biopolymer film and then released by individual millisecond-long light pulses
      generated by a near infrared (NIR) laser. Here graphene plays the dual role of a
      versatile substrate for temporary storage of drugs and an effective transducer of
      NIR-light into heat. Drug release appears to be narrowly confined within the size
      of the laser spot under noninvasive conditions and can be precisely dosed
      depending on the number of pulses. The approach proposed paves the way for tailor
      made pharmacological treatments of chronic diseases, including cancer, anaemia
      and diabetes. 

PMID- 24902635
TI  - The taming of oxygen: biocatalytic oxyfunctionalisations.
AB  - The scope and limitations of oxygenases as catalysts for preparative organic
      synthesis is discussed. 

PMID- 24902636
TI  - Bacterial tick-borne diseases caused by Bartonella spp., Borrelia burgdorferi
      sensu lato, Coxiella burnetii, and Rickettsia spp. among patients with cataract
      surgery.
AB  - BACKGROUND: Clinical data have shown that tick-borne diseases caused by Borrelia
      burgdorferi sensu lato, Bartonella spp., Coxiella burnetii, and Rickettsia spp.
      can affect the central nervous system, including the eye. The aim of this study
      was to establish a relationship between the incidence of cataract and evidence of
      bacterial infections transmitted by ticks. MATERIAL AND METHODS: Fluid with
      lenticular masses from inside of the eye and blood from 109 patients were tested
      by PCR and sequencing. Sera from patients and the control group were subjected to
      serological tests to search specific antibodies to the bacteria. RESULTS:
      Microbiological analysis revealed the presence of Bartonella sp. DNA in
      intraoperative specimens from the eye in 1.8% of patients. Serological studies
      have shown that infections caused by B. burgdorferi sensu lato and Bartonella sp.
      were detected in 34.8% and 4.6% of patients with cataract surgery, respectively.
      CONCLUSIONS: Presence of DNA of yet uncultured and undescribed species of
      Bartonella in eye liquid indicates past infection with this pathogen. Specific
      antibodies to B. burgdorferi sensu lato and Bartonella sp. are detected more
      frequently in patients with cataract compared to the control group. This could
      indicate a possible role of these organisms in the pathological processes within
      the eyeball, leading to changes in the lens. Further studies are needed to
      identify Bartonella species, as well as to recognize the infectious mechanisms
      involved in cataract development.

PMID- 24902637
TI  - Viability changes: microbiological analysis of dental casts.
AB  - BACKGROUND: This study evaluated the survival of the most prevalent oral bacteria
      and fungi (Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, and
      Candida albicans) in dental casts, and compared changes in the amounts of these
      microorganisms at different time intervals to determine how long dental casts may
      pose threat to the health of dental personnel and patients. MATERIAL AND METHODS:
      When manufacturing the casts, regular water was replaced with sterile distilled
      water, where suspensions of the studied bacteria or the fungus at certain
      concentrations were prepared. When the dental casts were fully set (solidified),
      plaster shavings were examined immediately after the contact of the studied
      microorganism with the plaster, as well as after 1, 2, 24, 48, 72, 96, and 120
      hours. Following that, we measured how the amount of the studied bacteria and
      fungi in 1 gram of the plaster changed within the studied period of time.
      RESULTS: Klebsiella pneumoniae survived in plaster for up to 4 days, and the
      reduction in the number of these bacteria became statistically significant after
      1 day (p<0.05). Staphylococcus aureus remained viable in plaster for up to 4
      days, and the number of these bacteria dropped after 1 day (p<0.05). Escherichia
      coli disappeared after 2 days, and a reduction was already observed after 2 hours
      (p<0.05). Candida albicans in plaster models died within 2 days, and a reduction
      in their number was observed after 1 day (p<0.05). CONCLUSIONS: The
      microorganisms did not multiply in the gypsum casts and their number
      significantly dropped instead of increasing.

PMID- 24902639
TI  - Pretherapy metabolic tumour volume is an independent predictor of outcome in
      patients with diffuse large B-cell lymphoma.
AB  - PURPOSE: We investigated the prognostic value of total metabolic tumour volume
      (TMTV) in diffuse large B-cell lymphoma (DLBCL). METHODS: TMTV was measured in
      114 patients with newly diagnosed DLBCL who underwent (18)F-FDG PET/CT at
      baseline before immunochemotherapy. TMTV was computed by summing the volumes of
      all lymphomatous lesions after applying the local SUVmax threshold of 41% using
      semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates
      of progression-free survival (PFS) and overall survival (OS). RESULTS: Median
      follow-up was 39 months. Average pretherapy TMTV was 509 +/- 568 cm(3). The 3
      year estimates of PFS were 77 % in the low metabolic burden group (TMTV <=550
      cm(3)) and 60% in the high metabolic burden group (TMTV >550 cm(3), p = 0.04),
      and prediction of OS was even better (87% vs. 60%, p = 0.0003). Cox regression
      showed independence of TMTV for OS prediction (p = 0.002) compared with other
      pretherapy indices of tumour burden, such as tumour bulk and the International
      Prognostic Index. CONCLUSION: Pretherapy TMTV is an independent predictor of
      outcome in patients with DLBCL.

PMID- 24902638
TI  - Silencing of BRCA2 decreases anoikis and its heterologous expression sensitizes
      yeast cells to acetic acid-induced programmed cell death.
AB  - Adhesion of normal epithelial cells to the extracellular matrix (ECM) is
      essential for survival. Cell detachment from ECM induces a specific form of
      programmed cell death (PCD) termed anoikis. BRCA2, a tumor suppressor gene whose
      mutations confer predisposition to cancer, has been implicated in the regulation
      of DNA repair, transcription, cell proliferation, and apoptosis. However, the
      potential role of BRCA2 in the regulation of anoikis has not been investigated.
      Here, we found that suppression of BRCA2 expression by short hairpin RNA promoted
      resistance to anoikis in prostate, breast and thyroid normal epithelial cells,
      which was accompanied by reduced caspases 3/7 levels and activity. Using yeast as
      a model, we assessed that expression of human BRCA2 does not induce cell death by
      itself but it can promote acetic acid-induced PCD (AA-PCD). Induction of BRCA2
      expression decreased cell survival and increased the number of cells positive to
      different apoptotic markers, including DNA fragmentation and phosphatidylserine
      externalization en route to AA-PCD. A higher increase in ROS levels occurred in
      the early phase of AA-PCD in BRCA2-expressing yeast cells compared with non
      expressing cells. Accordingly, a delay in the initial burst of ROS levels was
      observed in BRCA2-knockdown anoikis-resistant human cells. Treatment with the
      antioxidants N-acetylcysteine or ascorbic acid reduced sensitivity to anoikis in
      human cells and inhibited AA-PCD in yeast cells expressing BRCA2. Taken together,
      these results show a new function of BRCA2 protein as modulator of anoikis
      sensitivity through an evolutionarily-conserved molecular mechanism involving
      regulation of ROS production and/or detoxification by BRCA2 during PCD processes.

PMID- 24902640
TI  - Public awareness of head and neck cancers: a cross-sectional survey.
AB  - IMPORTANCE: Head and neck cancer (HNC) is responsible for substantial morbidity,
      mortality, and cost in the United States. Early detection and lifestyle risk
      factors associated with HNC, both determinants of disease burden and outcomes,
      are interrelated with public knowledge of this disease. Understanding of current
      public knowledge of HNC is lacking. OBJECTIVE: To assess awareness and knowledge
      of HNC among US adults. DESIGN, SETTING, AND PARTICIPANTS: Online survey of 2126
      randomly selected adults in the United States conducted in 2013. INTERVENTIONS:
      Online survey administration. MAIN OUTCOMES AND MEASURES: Subjective and
      objective assessment of knowledge of HNC including symptoms, risk factors, and
      association with the human papillomavirus. RESULTS: Self-reported respondent
      knowledge of HNC was low, with 66.0% reporting that they were "not very" or "not
      at all" knowledgeable. This did not vary significantly with tobacco use (P =
      .92), education (P = .053), sex (P = .07), or race (P = .02). Regarding sites
      comprising HNC, 22.1% of respondents correctly identified throat cancer, 15.3%
      mouth cancer, and 2.0% cancer of the larynx, with 21.0% incorrectly identifying
      brain cancer as HNC. Regarding symptoms, 14.9% of respondents identified "red or
      white sores that do not heal," 5.2% "sore throat," 1.3% "swelling or lump in the
      throat," and 0.5% "bleeding in the mouth or throat." Smoking and chewing or
      spitting tobacco were identified by 54.5% and 32.7% of respondents as risk
      factors for mouth and throat cancer, respectively. Only 0.8% of respondents
      identified human papillomavirus (HPV) infection as a risk factor for mouth and
      throat cancer, but specific questioning revealed that 12.8% were aware of the
      association between HPV infection and throat cancer whereas 70.0% of respondents
      were aware of the vaccine targeting HPV. CONCLUSIONS AND RELEVANCE: Self-reported
      and objective measures indicate that few American adults know much about HNC
      including risk factors such as tobacco use and HPV infection and common symptoms.
      Strategies to improve public awareness and knowledge of signs, symptoms, and risk
      factors may decrease the disease burden of HNC and are important topics for
      future research.

PMID- 24902641
TI  - 'Precipitation sign': a new radiological sign for spinal intramedullary
      tubercular abscess.
AB  - STUDY DESIGN: We came across two patients with holocord tuberculosis exhibiting
      similar radiological picture, which may aid in early diagnosis. OBJECTIVES: We
      have described a new radiological sign for early diagnosis of intramedullary
      tubercular abscess. SETTING: Observations from an endemic zone for tuberculosis
      (India). METHODS: Surgical excision followed by histological and microbiological
      examination and retrospective correlation of clinical-radiological-surgical and
      pathological picture. RESULTS: 'Precipitation sign' can be helpful in the
      diagnosis of intramedullary tuberculosis. CONCLUSION: Presence of an intradural
      extramedullary mass at the lower end of the spinal cord associated with holocord
      T2 hyperintensities of the spinal cord can be called as precipitation sign and
      should raise the suspicion of intramedullary tubercular abscess.

PMID- 24902642
TI  - Myelopathy due to lumbar disc herniation in the presence of a tethered cord.
AB  - STUDY DESIGN: Single case report. OBJECTIVES: To present a case of lumbar disc
      herniation causing compression of a tethered cord that was successfully treated
      with lumbar decompression and fusion. BACKGROUND: A tethered cord is a rare
      pathology associated with a congenital spinal malformation, spinal dysraphism.
      Furthermore, myelopathy due to lumbar disc herniation in the presence of a
      tethered cord is extremely rare. METHODS: Single case report. RESULTS: A 43-year
      old male with a history of spina bifida presented to our clinic for an evaluation
      of a progressive spastic gait disturbance and numbness in the lower limbs. A
      neurological examination revealed muscle weakness and pyramidal tract signs in
      the lower limbs. Magnetic resonance imaging of the lumbar spine showed disc
      herniation at L2-3 causing compression of a low-lying cord. Surgical
      intervention, including herniotomy via a posterolateral approach and instrumented
      posterolateral fusion, was performed, and a good outcome was achieved 1 year
      after the surgery. CONCLUSION: The potential for lumbar disc herniation in the
      presence of a tethered cord should be taken into account in the differential
      diagnosis of spinal pathologies causing spastic gait disturbances. Furthermore,
      posterior decompression and fusion is a useful treatment option in such cases.

PMID- 24902643
TI  - A rare case of multifocal intramedullary germinoma in cervical spinal cord.
AB  - STUDY DESIGN: Case report. OBJECTIVES: We present for the first time a patient
      with multifocal intramedullary cervical spinal cord germ cell tumors with
      elevated serum alpha-fetoprotein (AFP). SETTING: Nanjing Drum Tower Hospital, The
      Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
      METHODS: A 19-year-old girl experienced numbness in her right leg 10 months
      before diagnosis. The numbness gradually became severe and extended up to the
      thorax. Magnetic resonance imaging (MRI) visualized several intramedullary masses
      with intensive enhancement and extensive peritumoral edema in the spinal cord at
      the C3-T1 vertebral body levels. Administration of methylprednisolone caused no
      treatment effect. The largest mass, which was located at the T1 level inside the
      normal spinal cord and confirmed by naked eye observation, was completely
      extracted under a microscope. Postoperative pathological examination demonstrated
      the so-called 'two-cell pattern,' which is typical of germinoma with placental
      alkaline phosphatase expression. The serum level of AFP was 64.50 ng ml(-1)
      (normal range: 0-5 ng ml(-1)). The residual tumor was eliminated through
      radiation therapy (local 30 Gy) following surgery. Afterward, the patient's
      neurological deficits were improved but not resolved. RESULTS: Six years after
      surgery, no recurrence was encountered and the patient remained stable.
      CONCLUSION: Radiotherapy is the salvage therapy for spinal cord germinoma.
      Steroids were of no therapeutic value in the treatment of intramedullary spinal
      cord germinoma.

PMID- 24902644
TI  - Body composition changes after 12 months of FES cycling: case report of a 60-year
      old female with paraplegia.
AB  - STUDY DESIGN: Single-subject (female, 60 years of age) case. OBJECTIVES: The
      purpose of this case report is to document body composition changes in a 60-year
      old female with chronic paraplegia after 12 months of home-based functional
      electrical stimulation lower extremities cycling (FES-LEC). SETTING: Home-based
      FES-LEC with internet connection. Southeastern United States. METHODS: FES-LEC
      three sessions per week for 12 months in participant's home and monitored by the
      research staff via internet connection. Pre- and post-exercise program testing
      for body composition including percent body fat, fat mass (FM), lean mass (LM)
      and whole-body bone mineral density (BMD) via dual-energy x-ray absorptiometry
      (DXA). RESULTS: There was a 7.7% increase in total body LM and a 4.1% increase in
      legs LM. There was a 1.2% decrease in total body FM and a 9.9% decrease in legs
      FM. Percent body fat decreased from 48.4 to 46.3 and whole-body BMD was increased
      from 0.934 to 1.023, which resulted in an improvement in the DXA T-score from 
      2.4 to -1.3. CONCLUSION: Positive body compositional changes during this study
      support the idea that long-term FES-LEC can help restore healthier ratios of LM
      and FM and possibly decrease the risk of associated diseases. Increased whole
      body BMD provides hope that long-term FES-LEC may be beneficial regarding bone
      health.

PMID- 24902645
TI  - Effect of subcutaneous injection of botulinum toxin A on spinal cord injury
      associated neuropathic pain.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To present a case of spinal cord injury
      (SCI)-associated neuropathic pain treated with botulinum toxin A injection.
      SETTING: Outpatient SCI clinic. CASE REPORT: Description of a case in the context
      of relevant literature on the subject. RESULTS: A 51-year-old man with C3 AIS B
      tetraplegia (American Spinal Injury Association Impairment Scale B) visited our
      outpatient clinic due to severe ongoing neuropathic pain and associated allodynia
      and dysesthesia of the lower limbs. He had previously tried combinations of
      pregabalin, gabapentin and oxycontin but all failed to alleviate his neuropathic
      pain during the 2 years post trauma. With the patient's consent, he was treated
      with subcutaneous injections of clostridium type A botulinum toxin. Ten units of
      type A botulinum toxin subcutaneously injected into 10 most painful sites of each
      sole. The patient was reassessed at 4 and 8 weeks after his injection with
      botulinum toxin with significant improvement of his neuropathic pain. CONCLUSION:
      Subcutaneous injection of type A botulinum toxin was effective without side
      effects, on one case of refractory neuropathic pain due to SCI. This is the first
      article to report the use of type A botulinum toxin in neuropathic pain related
      to traumatic SCI.

PMID- 24902646
TI  - Organ-preserving treatment of an epididymal abscess in a patient with spinal cord
      injury.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To describe a case of successful organ
      preserving treatment of an epididymal abscess in a tetraplegic patient. SETTING:
      Spinal Cord Injury Rehabilitation Centre in Switzerland. METHODS: We present the
      clinical course of a patient with an epididymal abscess caused by multiresistant
      bacteria. As the patient declined surgical intervention, a conservative approach
      was induced with intravenous antibiotic treatment. As the clinical findings did
      not ameliorate, adjunctive homeopathic treatment was used. RESULTS: Under
      combined treatment, laboratory parameters returned to normal, and the epididymal
      abscess was rapidly shrinking. After 1 week, merely a subcutaneous liquid
      structure was detected. Fine-needle aspiration revealed sterile purulent liquid,
      which was confirmed by microbiological testing when the subcutaneous abscess was
      drained. Postoperative course was uneventful. CONCLUSIONS: As the risk for
      recurrent epididymitis is high in persons with spinal cord injury, an organ
      preserving approach is justified even in severe cases. Homeopathic treatment was
      a valuable adjunctive treatment in the above-mentioned case. Therefore,
      prospective studies are needed to further elucidate the future opportunities and
      limitations of classical homeopathy in the treatment of urinary tract infections.

PMID- 24902647
TI  - Hydronephrosis: an unusual complication of neurogenic bowel in a patient with
      spinal cord injury: a case report.
AB  - STUDY DESIGN/METHODS: Case report. OBJECTIVES: In this case report, a consequence
      of not following proper care of the bowel affecting the genitourinary system is
      reported and discussed. SETTING: United States. RESULTS/CONCLUSION: Neurogenic
      bowel and bladder can result from a spinal cord injury. It is necessary for
      spinal cord injury patients to continually follow recommended bladder and bowel
      care programs to decrease complications.

PMID- 24902648
TI  - Particulate polycyclic aromatic hydrocarbons (PAH) in the atmosphere of Bizerte
      city, Tunisia.
AB  - The particle-phase concentrations of polycyclic aromatic hydrocarbons (PAH) were
      determined in 13 air samples collected in an urban area of Bizerte (Tunisia)
      during 2009-2010. Atmospheric particulate samples were extracted by ultrasonic
      bath and analyzed by high-performance liquid chromatography with fluorescence
      detection. PAH were found in all the analyzed air samples and the most abundant
      compounds were pyrene, fluoranthene, benzo[g,h,i]perylene, benzo[b]fluoranthene,
      chrysene and benzo[a]pyrene. ?14-PAH concentrations ranging from 9.38 to 44.81 ng
      m(-3) with mean value of 25.39 ng m(-3). PAH diagnostic ratio source analysis
      revealed gasoline and diesel vehicular emissions as major sources. The mean total
      benzo[a]pyrene toxicity equivalent calculated for samples was 3.66 ng m(-3) and
      the mean contribution of the carcinogenic potency of benzo[a]pyrene was
      determined to be 55.8 %. Concentrations of particulate PAH in Bizerte city
      atmosphere were approximately eight times greater than sampled at a nearby rural
      site.

PMID- 24902649
TI  - Health risk assessment from mercury levels in bycatch fish species from the
      coasts of Guerrero, Mexico (Eastern Pacific).
AB  - With the aim of determining Hg distribution in muscle and liver of bycatch fish
      from Guerrero state in the Eastern Pacific Ocean and assess the potential risk to
      consumer, Hg was quantified in 14 species of bycatch fish. For the majority of
      fish the order of Hg levels was liver > muscle. The highest concentration
      corresponded to the liver of Isopisthus remifer (2.05 ug g(-1)) and the lowest
      (0.02 ug g(-1)) was detected in muscle of Prionotus sp. The highest hazard
      quotient (0.75) was found in the Mexican milkfish Micropogonias ectenes;
      considering all the individuals, mean hazard quotient was 0.336.

PMID- 24902650
TI  - Exposure assessment to glyphosate of two species of annelids.
AB  - Adult mortality, biomass, fecundity and viability of cocoons were studied in
      Eisenia fetida and Octolasion tyrtaeum, in response to glyphosate exposure in
      soil. Exposure tests were carried out following USEPA procedure, with five
      concentrations of glyphosate in soil and a control. O. tyrtaeum was more
      sensitive to the highest concentration of glyphosate (50,000 mg kg(-1)), with 100
      % mortality by day 7 of exposure, compared with 71 % for E. fetida. Although
      biomass of O. tyrtaeum was significantly different between the control and 5,000
      mg kg(-1) dose at day 14, E. fetida was not affected at that concentration, and
      only showed a significant weight loss after 7 days of exposure to 50,000 mg kg(
      1). Adverse effects upon adult fecundity and cocoon viability were observed at
      glyphosate concentrations of 5,000 mg kg(-1) and above. Adverse effects were
      observed at concentrations that greatly exceeded the recommended field
      application rates of glyphosate.

PMID- 24902651
TI  - Organochlorine pesticides and polychlorinated biphenyls in fish from Lake Awassa
      in the Ethiopian Rift Valley: human health risks.
AB  - Dietary intake of fish containing organic contaminants poses a potential threat
      to human health. In the present work, an assessment has been carried out to look
      at the human health risk associated with consumption of fish contaminated with
      organochlorine pesticides (OCPs) and polychlorinated biphenyles (PCBs) in certain
      fish species collected from Lake Hawassa, Ethiopia. The health risk assessment
      was made by comparing the concentrations of OCPs and PCBs in fish muscle tissues
      with reference doses given in the USEPA guidelines.
      Dichlorodiphenyltrichloroethanes (DDTs), endosulfans, PCBs and chloridanes were
      identified in fish species collected from Lake Hawassa. The most predominant
      pesticides were DDTs, with mean concentrations of SigmaDDT ranging from 19 to 56
      ng g(-1) wet weights. The highest concentrations of DDTs were found in Barbus
      intermedius, representing the highest trophic level. PCBs, DDT and endosulfan
      concentrations found in B. intermedius exceeded the reference dose for children
      between the ages of 0-1 year (with hazard index of above 1.0). Therefore,
      consumption of fish from a high trophic level (e.g. B. intermedius) from Lake
      Hawassa may pose a special health risk to children.

PMID- 24902652
TI  - Handgrip strength as a predictor for post bariatric body composition.
AB  - BACKGROUND: After bariatric surgery, the postoperative quality of weight loss is
      variable. The aim of weight loss treatment is to reduce fat mass while keeping
      fat free mass, in particular body cell mass (BCM), constant. Detection of low BCM
      is an important aspect of surgical follow up. Handgrip dynamometry is a rapid and
      inexpensive test to measure static muscle strength, which is an independent
      outcome indicator of various medical conditions. The objective of this study is
      to examine the change in handgrip strength after bariatric surgery and its
      predictive value for postoperative body composition. Furthermore, this study was
      carried out at the University Hospital, Germany. METHODS: Twenty-five patients
      who underwent a bariatric procedure (laparoskopic Roux-Y gastric bypass n=16 or
      sleeve resection n=9) were included in this study. Bioelectrical impedance
      analysis and hand-grip strength were measured preoperatively and repeated every 6
      weeks for 4 months. An analysis of variance was performed to observe the changes
      in these individual parameters. RESULTS: Postoperatively, all patients showed a
      significant decrease in the body mass index and body fat. The extracellular mass,
      BCM, and the lean mass of the patients remained constant. Handgrip strength
      showed no significant changes during the postoperative course. Nevertheless, the
      preoperative hand-grip strength showed a strong positive correlation with the
      postoperative body composition. CONCLUSIONS: This study showed no changes in the
      static muscle force after bariatric surgery. The preoperative handgrip strength
      was strongly correlated with postoperative body composition and may be used to
      identify patients who need more attention before surgery and in the early
      postoperative phase.

PMID- 24902653
TI  - Amelioration of glycemic control by sleeve gastrectomy and gastric bypass in a
      lean animal model of type 2 diabetes: restoration of gut hormone profile.
AB  - BACKGROUND: In obese diabetic patients, bariatric surgery has been shown to
      induce remission of type 2 diabetes. Along with weight loss itself, changes in
      gut hormone profiles after surgery play an important role in the amelioration of
      glycemic control. However, the potential of gastrointestinal surgery regarding
      diabetes remission in non-severely obese diabetic patients has yet to be defined.
      In the present experimental study, we explored the effect of established
      bariatric procedures with and without duodenal exclusion on glycemic control and
      gut hormone profile in a lean animal model of type 2 diabetes. METHODS: Forty 12-
      to 14-week-old non-obese diabetic Goto-Kakizaki (GK) rats were randomly assigned
      to four groups: control group (GKC), sham surgery (GKSS), sleeve gastrectomy
      (GKSG), and gastric bypass (GKGB). Age-matched Wistar rats served as a non
      diabetic control group (WIC). Glycemic control and plasma lipids were assessed at
      the beginning of the observation period and 4 weeks after surgery. Fasting and
      mixed meal-induced plasma levels of ghrelin, glucagon-like peptide-17-36 (GLP-1),
      and peptide tyrosine-tyrosine (PYY) were measured. RESULTS: In GK rats, glycemic
      control improved after sleeve gastrectomy (SG) and gastric bypass (GB). Mixed
      meal-induced gut hormone profiles in Wistar rats (WIC) were significantly
      different from those of sham-operated or control group GK rats. After SG and GB,
      GK rats showed a similar postprandial decrease in ghrelin as observed in non
      diabetic WIC. Following both surgical procedures, a significant meal-induced
      increase in PYY and GLP-1 could be demonstrated. CONCLUSIONS: SG and GB induce a
      similar improvement in overall glycemic control in lean diabetic rodents. Meal
      induced profiles of ghrelin, GLP-1, and PYY in GK rats are significantly modified
      by SG and GB and become similar to those of non-diabetic Wistar rats. Our data do
      not support the hypothesis that duodenal exclusion and early contact of food with
      the ileal mucosa alone explain changes in gut hormone profile in GK rats after
      gastrointestinal surgery.

PMID- 24902654
TI  - Effect of carbohydrate restriction in patients with hyperinsulinemic hypoglycemia
      after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Hyperinsulinemic hypoglycemia is a rare complication of Roux-en-Y
      gastric bypass (RYGB) surgery. Meals with a high carbohydrate (carb) content and
      high glycemic index (GI) may provoke these hypoglycemic attacks. The aim of this
      study is to assess the effects of reducing meal carb content and GI on glycemic
      responses in patients with post-RYGB hypoglycemia. METHODS: Fourteen patients
      with post-RYGB hypoglycemia underwent two meal tests: a mixed meal test (MMT)
      with a carb content of 30 g and a meal test with the low GI supplement, Glucerna
      SR 1.5(r) (Glucerna meal test (GMT)). Plasma glucose and serum insulin levels
      were measured for a period of 6 h. RESULTS: Peak glucose levels were reached at T
      30 during GMT and at T 60 during MMT, and they were 1.5 +/- 0.3 mmol/L lower
      during GMT than during MMT (7.5 +/- 0.4 vs 9.0 +/- 0.4 mmol/L, P < 0.005). GMT
      induced the most rapid rise in plasma insulin: at T 30 plasma, insulin was 30.7
      +/- 8.5 mU/L higher during GMT than during MMT (P < 0.005). None of the carb
      restricted meals induced post-prandial hypoglycemia. CONCLUSION: A 30-g carb
      restricted meal may help to prevent post-prandial hypoglycemia in patients with
      post-RYGB hypoglycemia. The use of a liquid, low GI, supplement offers no
      additional advantage.

PMID- 24902655
TI  - Perioperative fluid guidance with transthoracic echocardiography and pulse
      contour device in morbidly obese patients.
AB  - BACKGROUND: In bariatric surgery, non- or mini-invasive modalities for
      cardiovascular monitoring are addressed to meet individual variability in
      hydration needs. The aim of the study was to compare conventional monitoring to
      an individualized goal-directed therapy (IGDT) regarding the need of
      perioperative fluids and cardiovascular stability. METHODS: Fifty morbidly obese
      patients were consecutively scheduled for laparoscopic bariatric surgery
      (ClinicalTrials.gov Identifier: NCT01873183). The intervention group (IG, n=30)
      was investigated preoperatively with transthoracic echocardiography (TTE) and
      rehydrated with colloid fluids if a low level of venous return was detected.
      During surgery, IGDT was continued with a pulse-contour device (FloTracTM). In
      the control group (CG, n=20), conventional monitoring was conducted. The type and
      amount of perioperative fluids infused, vasoactive/inotropic drugs administered,
      and blood pressure levels were registered. RESULTS: In the IG, 213 +/- 204 mL
      colloid fluids were administered as preoperative rehydration vs. no preoperative
      fluids in the CG (p<0.001). During surgery, there was no difference in the fluids
      administered between the groups. Mean arterial blood pressures were higher in the
      IG vs. the CG both after induction of anesthesia and during surgery (p=0.001 and
      p=0.001). CONCLUSIONS: In morbidly obese patients suspected of being hypovolemic,
      increased cardiovascular stability may be reached by preoperative rehydration.
      The management of rehydration should be individualized. Additional invasive
      monitoring does not appear to have any effect on outcomes in obesity surgery.

PMID- 24902656
TI  - Continuity of care in community midwifery.
AB  - Continuity of care is often critical in delivering high quality health care.
      However, it is difficult to achieve in community health care where shift patterns
      and a need to minimise travelling time can reduce the scope for allocating staff
      to patients. Community midwifery is one example of such a challenge in the
      National Health Service where postnatal care typically involves a series of home
      visits. Ideally mothers would receive all of their antenatal and postnatal care
      from the same midwife. Minimising the number of staff-handovers helps ensure a
      better relationship between mothers and midwives, and provides more opportunity
      for staff to identify emerging problems over a series of home visits. This study
      examines the allocation and routing of midwives in the community using a variant
      of a multiple travelling salesmen problem algorithm incorporating staff
      preferences to explore trade-offs between travel time and continuity of care.
      This algorithm was integrated in a simulation to assess the additional effect of
      staff availability due to shift patterns and part-time working. The results
      indicate that continuity of care can be achieved with relatively small increases
      in travel time. However, shift patterns are problematic: perfect continuity of
      care is impractical but if there is a degree of flexibility in the visit
      schedule, reasonable continuity is feasible. 

PMID- 24902658
TI  - The impact of on-site attending radiologist overnight coverage on radiology
      resident learning: a preliminary assessment.
AB  - The objective of this study is to assess the impact of on-site attending
      radiologist overnight coverage on resident education during transition to 24/7
      attending coverage. The study was exempted from IRB review. An anonymous survey
      was sent to 9 second year radiology residents who completed their first night
      call rotation (NC) with an attending radiologist (group 1) and 18 residents who
      completed their first NC prior to overnight attending coverage (group 2). This
      addressed anxiety level prior to NC, work pace, autonomy and confidence, and
      attending feedback, with responses graded on a five-point scale. Statistical
      analysis was performed using Spearman's rho correlation coefficient. Diagnostic
      Radiology In-Training (DXIT(TM)) exam scores were collected prior to and
      following completion of the NC rotation, and results were compared. Case volume
      before and after the transition was recorded. p value <0.05 indicated statistical
      significance. Eight out of nine residents in group 1 and 16 out of/18 residents
      in group 2 completed the survey. Group 1 was more likely to report working at a
      comfortable pace (p = 0.008) and receiving attending feedback (p = 0.004) than
      group 2. A non-significant trend towards reduced anxiety prior to NC was present
      in group 1 (p = 0.077). No difference in independence (p = 0.918), autonomy (p =
      0.635), or confidence during (p = 0.431) or after NC (p = 1.00) was identified.
      DXIT(TM) scores were not significantly different between the two groups (p =
      0.396). While overall case volume dictated by residents increased, fewer plain
      radiographs were dictated. Overnight attending coverage provides a more
      comfortable pace of study interpretation and increased attending feedback without
      decreasing resident independence or DXIT(TM) scores. Plain radiograph
      interpretation may need to be further emphasized.

PMID- 24902657
TI  - The impact of introducing a no oral contrast abdominopelvic CT examination
      (NOCAPE) pathway on radiology turn around times, emergency department length of
      stay, and patient safety.
AB  - This investigation evaluates the impact of the no oral contrast abdominopelvic CT
      examination (NOCAPE) on radiology turn around time (TAT), emergency department
      (ED) length of stay (LOS), and patient safety metrics. During a 12-month period
      at two urban teaching hospitals, 6,409 ED abdominopelvic (AP) CTs were performed
      to evaluate acute abdominal pain. NOCAPE represented 70.9 % of all ED AP CT
      examinations with intravenous contrast. Data collection included patient
      demographics, use of intravenous (IV) and/or oral contrast, order to complete and
      order to final interpretation TAT, ED LOS, admission, recall and bounce back
      rates, and comparison and characterization of impressions. The NOCAPE pathway
      reduced median order to complete TAT by 32 min (22.9 %) compared to IV and oral
      contrast AP CT examinations (traditional pathway) (P < 0.001). Median order to
      final TAT was 2.9 h in NOCAPE patients and 3.5 h in the traditional pathway, a 36
      min (17.1 %) reduction (P < 0.001). Overall, the NOCAPE pathway reduced ED LOS by
      a median of 43 min (8.8 %) compared to the traditional pathway (8.2 vs 7.5 h) (P
      = 0.003). Recall and bounce back rates were 3.2 %, and only one patient had
      change in impression after oral contrast CT was repeated. The NOCAPE pathway is
      associated with decreased radiology TAT and ED LOS metrics. The authors suggest
      that NOCAPE implementation in the ED setting is safe and positively impacts both
      radiology and emergency medicine workflow. 

PMID- 24902659
TI  - Diabetic foot ulcer: an evidence-based treatment update.
AB  - BACKGROUND: Diabetic foot ulcers (DFUs) are extremely debilitating and difficult
      to treat. Multidisciplinary management, patient education, glucose control,
      debridement, offloading, infection control, and adequate perfusion are the
      mainstays of standard care endorsed by most practice guidelines. Adjunctive
      therapies represent new treatment modalities endorsed in recent years, though
      many lack significant high-powered studies to support their use as standard of
      care. OBJECTIVE: This update intends to identify recent, exclusively high level,
      evidence-based evaluations of DFU therapies. Furthermore, it suggests a direction
      for future research. METHODS: PubMed, Embase, Ovid Technologies, CINAHL,
      Cochrane, and Web of Science databases were systematically searched for recent
      systematic reviews published after 2004, and randomized controlled trials
      published in 2012-2013 that evaluated treatment modalities for DFUs. These papers
      are reviewed and the quality of available evidence is discussed. RESULTS: A total
      of 34 studies met inclusion criteria. Studied therapies include debridement, off
      loading, negative pressure therapy, dressings, topical therapies, hyperbaric
      oxygen therapy, growth factors, bioengineered skin substitutes, electrophysical
      therapy, and alternative therapy. Good-quality evidence is lacking to justify the
      use of many of these therapies, with the exception of standard care (offloading,
      debridement) and possibly negative pressure wound therapy. LIMITATIONS: There is
      an overall lack of high-level evidence in new adjunctive management of DFU.
      Comparison of different treatment modalities is difficult, since existing studies
      are not standardized. CONCLUSIONS: Many therapeutic modalities are available to
      treat DFU. Quality high-level evidence exists for standard care such as off
      loading. Evidence for adjunctive therapies such as negative pressure wound
      therapy, skin substitutes, and platelet-derived growth factor can help guide
      adjunctive care but limitations exist in terms of evidence quality.

PMID- 24902660
TI  - The -1154 G/A VEGF gene polymorphism is associated with the incidence of basal
      cell carcinoma in patients from northern Poland.
AB  - Vascular endothelial growth factor (VEGF) is believed to play a crucial role in
      neoplastic angiogenesis. Although the genetic background of basal cell carcinoma
      (BCC) has been analyzed in some papers, the mechanism of BCC pathogenesis is not
      fully understood. To the best of our knowledge, VEGF gene polymorphisms have not
      yet been explored. The aim of the study was to asses the frequency of three
      polymorphisms in the VEGF gene (-1154 G/A, -460 T/C and +405 G/C) in patients of
      Polish origin with BCC and control group. In addition, VEGF serum levels of
      patients with BCC and controls were measured. The study involved 180 patients (96
      women, 84 men) with BCC and a mean age of 68.9 +/- 11.8, and 215 healthy age- and
      sex-matched volunteers. The VEGF polymorphisms at positions -1154 and +405 were
      analyzed using the amplification refractory mutation system polymerase chain
      reaction method. To assess the VEGF gene polymorphism at position -460, we used
      the polymerase chain reaction restriction fragment length polymorphism method.
      Serum levels of VEGF protein were measured using the ELISA test. The presence of
      the G allele (GA or GG) in the -1154 VEGF polymorphism was associated with an
      increased risk of BCC development (OR = 7.28, p < 0.0001). Furthermore, the
      carriers of the AA genotype in -1154 VEGF polymorphism showed significantly
      reduced risks of BCC (OR = 0.14, p < 0.0001). It was also shown that the GTC
      haplotype of VEGF predisposes to BCC development (OR = 1.69, p = 0.013), while
      the presence of the ATG haplotype significantly reduces this risk (OR = 0.17, p =
      0.00001). We have found significantly increased VEGF serum levels among BCC
      patients, in comparison with the healthy controls (mean 596.7 +/- 393.5 pg/ml;
      range 60.1-931.4 vs. 255.9 +/- 174.6 pg/ml; range 42.2-553.0 pg/ml; p < 0.0004).
      The serum levels of VEGF significantly correlated with tumor size: r = 0.41, p <
      0.0001. Our results testify to the importance of -1154 G/A VEGF gene
      polymorphisms in altering the risk of BCC among the population from northern
      Poland.

PMID- 24902661
TI  - Sequential molecular analysis of circulating MCAM/MUC18 expression: a promising
      disease biomarker related to clinical outcome in melanoma.
AB  - MCAM/MUC18 is a cell adhesion molecule associated with higher incidence of
      relapse in melanoma. The purpose of our study was to evaluate its role as a
      promising disease biomarker of progression through sequential molecular
      MCAM/MUC18 RT-PCR assay on serial blood samples collected during the clinical
      follow-up of 175 melanoma patients in different American Joint Committee on
      Cancer (AJCC) stages. MCAM/MUC18 molecular detection, found at least once in 22
      out of the 175 patients, was significantly associated with poor prognosis and
      death (p < 0.001), regardless of the AJCC stages. Positive expression, either if
      primarily present or later acquired, was associated with melanoma progression,
      whereas patients primarily negative or with subsequent loss gained clinical
      remission or stable disease, even if in advanced stages (p < 0.005). Six AJCC
      advanced stages always MCAM/MUC18 negative are in complete remission or with a
      stable disease (p < 0.007). Semiquantitative immunohistochemical MCAM/MUC18
      staining on corresponding primary melanomas was related to peripheral molecular
      expression. Correlations between circulating molecular and tissutal
      immunohistochemical detection, primary tumour thickness, AJCC stages and clinical
      outcome were statistically evaluated using Student's t test, ANOVA, Spearman's
      rank correlation test, Pearson chi (2)-test and McNemar's test. In our
      investigation, MCAM/MUC18 expression behaves as a "molecular warning of
      progression" even in early AJCC patients otherwise in disease-free conditions.
      Achievement of this molecule predicted the emergence of a clinically apparent
      status, whereas absence or persistent loss was related to a stable disease or to
      a disease-free status. If confirmed in larger case series, MCAM/MUC18 molecular
      expression could predict good or poor clinical outcome, possibly becoming a
      promising prognostic factor.

PMID- 24902662
TI  - Synphilin-1A is a phosphoprotein phosphatase 1-interacting protein and affects
      PPP1 sorting to subcellular compartments.
AB  - Lewy bodies (LBs) are synphilin-1 (Sph1)-containing aggregates and histological
      hallmarks of Parkinson's disease. Therefore, understanding processes which
      modulate the aggregation of Sph1, or its isoform Sph1A, will contribute to our
      understanding of LBs formation. Protein phosphorylation promotes aggregation, but
      protein phosphatases with activity towards Sph1 have not been described. The
      present study documents the identification of a novel Sph1A/phosphoprotein
      phosphatase 1 (PPP1) complex and unravels its regulatory effect on Sph1A
      aggregation. Using yeast co-transformation and overlay blot assay, the
      interaction between Sph1A and PPP1 was mapped to the Sph1A RVTF motif. Then,
      Sph1A overexpression in human embryonic kidney 293 cells demonstrated that Sph1A
      specifically targets endogenous PPP1 isoforms to inclusion bodies and that
      Sph1A/PPP1 complex disruption enhances inclusion bodies formation. Finally, as
      Sph1A interacted with PPP1CC2, a PPP1 sperm-specific isoform, Sph1 and Sph1A
      expression was addressed in male germ cells by qRT-PCR, revealing high expression
      levels in round spermatids. Together, these observations established Sph1A as a
      novel PPP1-interacting protein able to affect PPP1 sorting to subcellular
      compartments and Sph1A/PPP1 complex as a negative modulator of LBs formation.
      Contrarily, in physiological conditions, Sph1 isoforms are pointed as putative
      participants in vesicle dynamics with implications in neurotransmission and
      spermiogenesis. 

PMID- 24902663
TI  - MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor PDCD4
      and promotes cell transformation, proliferation, and metastasis in renal cell
      carcinoma.
AB  - OBJECTIVES: MiR-21 induces neoplastic transformation, cell proliferation, and
      metastasis and downregulates programmed cell death4 (PDCD4) in some cancers. The
      aim of this study was to investigate the roles and interactions of PDCD4 and miR
      21 in human renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 32
      paired tumor and normal tissue specimens from RCC patients as well as three renal
      cancer cell lines (786-O, A498, caki-1) and one normal epithelial kidney cell
      line (HK-2) were studied. The expression levels of PDCD4 (protein and mRNA) and
      miR-21 were examined by Western blot analysis and by qRT-PCR and luciferase
      reporter assays. Furthermore, we transfected 786-O cells with pre-miR-21 (mimics)
      and anti-miR-21 (inhibitor) and then again analyzed the expression of PDCD4
      protein and mRNA, and determined cell proliferation and transformation
      capabilities by EDU and soft agar colony formation assay. RESULTS: MiR-21
      expression was significantly upregulated in RCC, metastatic RCC specimens and
      renal cancer cell lines (A498, 786-O, caki-1) compared to normal non-metastatic
      RCC specimens and HK-2 cells (P<0.05). In contrast, PDCD4 protein expression
      significantly decreased (P<0.05), whereas PDCD4 mRNA expression remained
      unaltered (P>0.05). Moreover, we observed a significant reduction in PDCD4
      protein levels in miR-21mimic-transfected cells, but a significant increase in
      miR-21inhibitor-transfected cells (P<0.05), whereas PDCD4 mRNA was practically
      unaltered (P>0.05). Furthermore, miR-21mimic-transfected cells exhibited
      increased cell proliferation and transformation capacity according to EDU
      analysis and soft agar formation assay, whereas miR-21inhibitor-transfected cells
      exhibited the opposite phenomenon(P<0.05). CONCLUSIONS: MiR-21 not only promoted
      cancer cell hyperplasia and contributed to tumor cell transformation and
      metastasis, but also post-transcriptionally downregulated PDCD4 protein
      expression. PDCD4 and miR-21 expression levels potentially play an important role
      in renal cell cancer.

PMID- 24902664
TI  - Non-initiation and early discontinuation of adjuvant trastuzumab in women with
      localized HER2-positive breast cancer.
AB  - One year of trastuzumab therapy is recommended for women with HER2-positive
      breast cancer >= 1.0 cm in size to increase survival and is considered for women
      with tumors 0.5-0.9 cm in size. We analyzed compliance with trastuzumab among
      women with HER2-positive breast cancer in a prospective cohort study. Of 1145
      recruited patients with breast cancer, 152 were HER2-positive (13.2 %), of whom
      126 had tumors >= 1.0 cm; 110/126 (87.3 %) of these initiated trastuzumab. Non
      receipt was associated with older age, better prognosis tumors, and with non
      receipt of adjuvant chemotherapy. Of the 110 who initiated treatment, 18 (15 %)
      did not complete treatment, 15 (83 %) of them because of cardiotoxicity. Of 20
      women with tumors 0.5-0.9 cm, 5 (25 %) initiated trastuzumab. Compliance with
      trastuzumab was very high among those with HER2-positive breast cancer, as was
      the completion of the recommended therapy.

PMID- 24902665
TI  - Control of neural stem cell self-renewal and differentiation in Drosophila.
AB  - The neural stem cells of Drosophila, called neuroblasts, have the ability to self
      renew and at the same time produce many different types of neurons and glial
      cells. In the central brain and ventral ganglia, neuroblasts are specified and
      delaminate from the neuroectoderm during embryonic development under the control
      of proneural and neurogenic genes. In contrast, in the optic lobes,
      neuroepithelial cells are transformed into neuroblasts postembryonically by a
      spatial wave of proneural gene expression. Central brain and ventral nerve cord
      neuroblasts manifest a short embryonic proliferation period followed by a stage
      of quiescence and then undergo a prolonged postembryonic proliferation period
      during which most of the differentiated neurons of the adult CNS are generated.
      While most neuroblasts belong to a type I class that produces neuronal lineages
      through non-self-renewing ganglion mother cells, a small subset of type II
      neuroblasts generates exceptionally large neuronal lineages through self-renewing
      intermediate progenitor cells that have a transit amplifying function. All
      neuroblasts in the CNS generate their neural progeny through an asymmetric cell
      division mode in which the interplay of apical complex and basal complex
      molecules in the mitotically active progenitor results in the segregation of cell
      fate determinants into the smaller more differentiated daughter cell. Defects in
      this molecular control of asymmetric cell division in neuroblasts can result in
      brain tumor formation. Proliferating neuroblast lineages in the developing CNS
      utilize transcription factor cascades as a generic mechanism for temporal
      patterning and birth order-dependent determination of differential neural cell
      fate. This contributes to the generation of a remarkable diversity of cell types
      in the developing CNS from a surprisingly small set of neural stem cell-like
      precursors. 

PMID- 24902667
TI  - Syncytin-1 in differentiating human myoblasts: relationship to caveolin-3 and
      myogenin.
AB  - Myoblasts fuse to form myotubes, which mature into skeletal muscle fibres. Recent
      studies indicate that an endogenous retroviral fusion gene, syncytin-1, is
      important for myoblast fusions in man. We have now expanded these data by
      examining the immunolocalization of syncytin in human myoblasts induced to fuse.
      Additionally, we have compared the localization of syncytin with the localization
      of caveolin-3 and of myogenin, which are also involved in myoblast fusion and
      maturation. Syncytin was localized to areas of the cell membrane and to
      filopodial structures connecting myoblasts to each other and to myotubes. Weaker
      staining was present over intracellular vesicles and tubules. Caveolin-3 was
      detected in the sarcolemma and in vesicles and tubules in a subset of myoblasts
      and myotubes. The strongest staining occurred in multinucleated myotubes. Wide
      field fluorescence microscopy indicated a partial colocalization of syncytin and
      caveolin-3 in a subset of myoblasts. Super-resolution microscopy showed such
      colocalization to occur in the sarcolemma. Myogenin was restricted to nuclei of
      myoblasts and myotubes and the strongest staining occurred in multinucleated
      myotubes. Syncytin staining was observed in both myogenin-positive and myogenin
      negative cells. Antisense treatment downmodulated syncytin-1 expression and
      inhibited myoblast cell fusions. Importantly, syncytin-1 antisense significantly
      decreased the frequency of multinucleated myotubes demonstrating that the
      treatment inhibited secondary myoblast fusions. Thus, syncytin is involved in
      human myoblast fusions and is localized in areas of contact between fusing cells.
      Moreover, syncytin and caveolin-3 might interact at the level of the sarcolemma. 

PMID- 24902669
TI  - Effects of Ce doping on the luminescent property of Ca3 SiO4 Cl2 :Eu phosphor for
      green lighting.
AB  - White light-emitting diodes (LEDs) for green lighting are new solutions for
      energy saving and environmental protection. Ca3 SiO4 Cl2 :Ce,Eu is an efficient
      phosphor for white LEDs. Effective energy transfer from Ce(3+) to Eu(2+) occurs
      in Ca3 SiO4 Cl2 :Ce,Eu due to good spectrum overlap between the emission band of
      Ca3 SiO4 Cl2 :Ce and the excitation band of Ca3 SiO4 Cl2 :Eu, and hues vary
      systematically from blue to green at different Ce concentrations. A great
      improvement in the luminescent property of Ca3 SiO4 Cl2 :Eu has been observed on
      Ce(3+) doping, which is attributed to energy transfer from Ce(3+) to Eu(2+) and
      an increase in the number of luminescent centers (Eu(2+) ) on Ce doping. The
      optimal sample has a quantum efficiency of up to 75%, and can be an efficient
      green phosphor for white LEDs.

PMID- 24902670
TI  - Distribution, characterization, and exposure of MC252 oil in the supratidal beach
      environment.
AB  - The distribution and characteristics of MC252 oil:sand aggregates, termed surface
      residue balls (SRBs), were measured on the supratidal beach environment of oil
      impacted Fourchon Beach in Louisiana (USA). Probability distributions of 4
      variables, surface coverage (%), size of SRBs (mm(2) of projected area), mass of
      SRBs per m(2) (g/m(2)), and concentrations of polycyclic aromatic hydrocarbons
      (PAHs) and n-alkanes in the SRBs (mg of crude oil component per kg of SRB) were
      determined using parametric and nonparametric statistical techniques. Surface
      coverage of SRBs, an operational remedial standard for the beach surface, was a
      gamma-distributed variable ranging from 0.01% to 8.1%. The SRB sizes had a mean
      of 90.7 mm(2) but fit no probability distribution, and a nonparametric ranking
      was used to describe the size distributions. Concentrations of total PAHs ranged
      from 2.5 mg/kg to 126 mg/kg of SRB. Individual PAH concentration distributions,
      consisting primarily of alkylated phenanthrenes, dibenzothiophenes, and
      chrysenes, did not consistently fit a parametric distribution. Surface coverage
      was correlated with an oil mass per unit area but with a substantial error at
      lower coverage (i.e., <2%). These data provide probabilistic risk assessors with
      the ability to specify uncertainty in PAH concentration, exposure frequency, and
      ingestion rate, based on SRB characteristics for the dominant oil form on beaches
      along the US Gulf Coast.

PMID- 24902671
TI  - Early adversity, personal resources, body dissatisfaction, and disordered eating.
AB  - OBJECTIVE: Early adverse experiences have been associated with disordered eating,
      but the mechanisms underlying that association are not well understood. The
      purpose of this study is to test a structural equation model in which early
      adversity is associated with disordered eating via intrapersonal resources,
      interpersonal resources, and body dissatisfaction. METHOD: Female university
      students (n = 748) completed a series of questionnaires online, including
      measures of early adverse experiences, intrapersonal resources (self-esteem and
      personal growth initiative), interpersonal resources (gratitude and social
      support), body dissatisfaction, and disordered eating and exercising to lose
      weight. RESULTS: Structural equation modeling indicated that early adverse
      experiences were negatively associated with interpersonal and intrapersonal
      resources. Intrapersonal resources were negatively associated with body
      dissatisfaction, whereas interpersonal resources were positively associated with
      body dissatisfaction (although negative bivariate correlations in this latter
      case suggest possible suppression effects). Finally, body dissatisfaction was
      associated with a range of disordered eating behaviors and exercise. DISCUSSION:
      Early adverse experiences are important to consider in models of disordered
      eating. The results of this study highlight potential points of early prevention
      efforts, such as improving personal resources for those who experience early
      adversity, to help reduce the risk of body dissatisfaction and disordered eating
      in young women.

PMID- 24902666
TI  - Segregating neural and mechanosensory fates in the developing ear: patterning,
      signaling, and transcriptional control.
AB  - The vertebrate inner ear is composed of multiple sensory receptor epithelia, each
      of which is specialized for detection of sound, gravity, or angular acceleration.
      Each receptor epithelium contains mechanosensitive hair cells, which are
      connected to the brainstem by bipolar sensory neurons. Hair cells and their
      associated neurons are derived from the embryonic rudiment of the inner ear
      epithelium, but the precise spatial and temporal patterns of their generation, as
      well as the signals that coordinate these events, have only recently begun to be
      understood. Gene expression, lineage tracing, and mutant analyses suggest that
      both neurons and hair cells are generated from a common domain of neural and
      sensory competence in the embryonic inner ear rudiment. Members of the Shh, Wnt,
      and FGF families, together with retinoic acid signals, regulate transcription
      factor genes within the inner ear rudiment to establish the axial identity of the
      ear and regionalize neurogenic activity. Close-range signaling, such as that of
      the Notch pathway, specifies the fate of sensory regions and individual cell
      types. We also describe positive and negative interactions between basic helix
      loop-helix and SoxB family transcription factors that specify either neuronal or
      sensory fates in a context-dependent manner. Finally, we review recent work on
      inner ear development in zebrafish, which demonstrates that the relative timing
      of neurogenesis and sensory epithelial formation is not phylogenetically
      constrained. 

PMID- 24902672
TI  - Cell retention by encapsulation for the cultivation of Jurkat cells in fixed and
      fluidized bed reactors.
AB  - Jurkat cells are accepted model cells for primary human T lymphocytes, for
      example, in medical research. Their growth to tissue-like cell densities (up to
      100 * 10(6)  cells/mLcapsule ) in semi-permeable (molecular weight cut off
      <10,000 Da) sodium cellulose sulfate/poly(diallyldimethylammonium chloride)
      polyelectrolyte capsules has previously been shown by us [Werner et al. (2013).
      Use of the mitochondria toxicity assay for quantifying the viable cell density of
      microencapsulated jurkat cells. Biotechnol Prog 29(4): 986-993]. Herein, we
      demonstrate that encapsulation can be used to retain the cells in continuously
      operated bioreactors, which opens new possibilities for research, for example,
      the use of Jurkat cells in pulse response experiments under steady state
      conditions. Two reactor concepts are presented, a fluidized and a fixed bed
      reactor. A direct comparison of the growth kinetics in batch and repeated batch
      spinner cultivations, that is, under conditions where both encapsulated and non
      encapsulated cells can be cultivated under otherwise identical conditions, showed
      that maximum specific growth rates were higher for the encapsulated than for the
      non-encapsulated cells. In the subsequent batch and repeated batch bioreactor
      experiments (only encapsulated cells), growth rates were similar, with the
      exception of the fixed bed batch reactor, where growth kinetics were
      significantly slower. Concomitantly, a significant fraction of the cells towards
      the bottom of the bed were no longer metabolically active, though apparently not
      dead. In the repeated batch fluidized bed reactor cellular division could be
      maintained for more than two weeks, albeit with a specific growth rate below the
      maximum one, leading to final cell densities of approximately 180 * 10(6) 
      cell/gcapsule . At the same time, the cell cycle distribution of the cells was
      shifted to the S and G2/M phases.

PMID- 24902673
TI  - Qigong versus exercise therapy for chronic low back pain in adults--a randomized
      controlled non-inferiority trial.
AB  - BACKGROUND: The value of qigong in the treatment of chronic low back pain is
      unclear. In a randomized controlled trial, we evaluated whether qigong is non
      inferior to exercise therapy in patients with chronic low back pain. METHODS:
      German outpatients (aged 46.7 +/- 10.4) with chronic low back pain [mean visual
      analogue scale (VAS), 53.9 +/- 12.5 mm] were enrolled and randomly allocated in a
      1:1 ratio to receive either qigong (64 patients, 12 sessions with 1 * 90 min/week
      over 3 months) or exercise therapy (63 patients, 12 sessions 1 * 60 min/week).
      The primary outcome measure was the average pain intensity over the last 7 days
      on a VAS (0-100 mm, 0 = no pain, 100 = worst imaginable pain, non-inferiority
      margin = 5 mm) after 3 months. Follow-up was measured after 6 and 12 months.
      RESULTS: The mean adjusted low back pain intensity after 3 months was 34.8 mm
      [95% confidence interval (CI) 29.5; 40.2] in the qigong group and 33.1 mm (95% CI
      27.7; 38.4) in the exercise group. Non-inferiority of the qigong group compared
      with the exercise group failed to show statistical significance (p = 0.204). In
      both groups, 10 patients reported suspected adverse reactions (e.g., muscle
      soreness, dizziness, pain) the total number was comparable in both groups (qigong
      n = 40, exercise n = 44). CONCLUSIONS: Qigong was not proven to be non-inferior
      to exercise therapy in the treatment of chronic low back pain. Its role in the
      prevention of chronic low back pain might be addressed in further studies.

PMID- 24902674
TI  - The effect of zinc-carbonate hydroxyapatite versus fluoride on enamel surfaces
      after interproximal reduction.
AB  - The aim of this study was to qualitatively investigate the effects of a zinc
      carbonate hydroxyapatite (Zn-CHA) containing toothpaste on stripped enamel
      morphology in a pH cycling model in vitro and to compare the efficacy of this
      toothpaste versus fluoride one which still represent the gold standard to
      remineralize early enamel lesions. Twenty-one extracted lower incisors underwent
      to interproximal enamel reduction with metal strips (Horico 80 um) on both mesial
      and distal surfaces. They were then sliced into mesial and distal halves and the
      42 samples obtained were randomly assigned to 3 groups of 14 enamel specimens
      each. For 8 days, teeth were placed in lactic acid solution for 2 h three times a
      day with 2 h distilled water preservation in between. After each demineralization
      bath, samples of Group A were brushed with Zn-CHA containing toothpaste while
      samples of Group B were brushed with 1,400 ppm fluoride dentifrice for 5 min
      before immersion into water. Group C of untreated samples served as control. All
      the samples were then prepared for scanning electron microscopy (SEM) analysis. A
      score rating system was used to perform a non-parametric statistical analysis. No
      statistically significant differences were found between the samples brushed with
      fluoride toothpaste and those untreated (Groups B and C) where the highest grade
      of damage was found, while the lowest grade was recorded in the samples brushed
      with Zn-CHA (Group A) and there was a statistically significant difference
      between this group and the other two groups.

PMID- 24902675
TI  - Synchrotron-radiation-based soft X-ray electron spectroscopy applied to
      structural and chemical characterization of isolated species, from molecules to
      nanoparticles.
AB  - With its extended tunability from the IR to hard X-rays and the exceptional
      spectral brightness offered by the 3rd generation storage rings, synchrotron
      radiation (SR) is an invaluable investigation tool. Major methodological
      developments are now available, and are applied to simple, isolated atoms and
      molecules (which can be often modeled ab initio) and are then extended to the
      investigation of more and more complex species, up to soft and hard condensed
      matter. The present article highlights, with a few examples, the most recent
      achievements in SR-based soft X-ray electron spectroscopy applied to the
      structural characterization of isolated species of increasing complexity, from
      molecules and clusters to nanoparticles. Special attention is devoted to very
      high resolution studies of single molecules revealing electron diffraction and
      interference effects, as well as detailed information about their potential
      energy surfaces. These achievements are only possible based on the new
      opportunities offered by the most advanced SR facilities. 

PMID- 24902676
TI  - Nanoparticles of esterified polymalic acid for controlled anticancer drug
      release.
AB  - Esterification of microbial poly(malic acid) is performed with either ethanol or
      1-butanol to obtain polymalate conjugates capable to form nanoparticles (100-350
      nm). Degradation under physiological conditions takes place with release of malic
      acid and the corresponding alcohol as unique degradation products. The anticancer
      drugs Temozolomide and Doxorubicin are encapsulated in nanoparticles with
      efficiency of 17 and 37%, respectively. In vitro drug release assays show that
      Temozolomide is almost completely discharged in a few hours whereas Doxorubicin
      is steadily released along several days. Drug-loaded nano-particles show
      remarkable effectiveness against cancer cells. Partially ethylated poly(malic
      acid) nano-particles are those showing the highest cellular uptake. 

PMID- 24902677
TI  - Crystallization from the amorphous state: nucleation-growth decoupling,
      polymorphism interplay, and the role of interfaces.
AB  - The physical stability of the amorphous state is governed by crystallization,
      which results from the complex interplay of nucleation and growth processes.
      These processes can be further complicated by the preferred initial nucleation of
      less-stable phases, and interpretation requires the evaluation of the relative
      roles of structure, dynamics, and thermodynamics on the kinetics of the
      recrystallization. As a contribution to this issue, we reanalyze data sets
      concerning recrystallization of two pharmaceutical compounds: L-arabitol and RS
      ibuprofen. These compounds share the property of being good glass formers and
      present monotropic polymorphism. In the present analysis, we are mainly focusing
      on the localization of nucleation and growth zones and the role of a transient
      crystallization of the metastable phase. On the basis of the elementary theories,
      the results offer the opportunity to discuss the impact of interfacial energies,
      molecular mobility, crystal disorder, liquid short-range order, and crack
      formation in the glass.

PMID- 24902678
TI  - Chinese cohort study of chronic kidney disease: design and methods.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a common disorder associated with
      multiple adverse clinical consequences, especially cardiovascular risk and end
      stage renal disease. A recent national survey demonstrated that CKD has become a
      leading health problem in China. There is an urgent need to implement an in-depth
      investigation of the CKD burden and also to explore underlying mechanisms of CKD
      progression and it association with adverse consequences. METHODS: The Chinese
      Cohort Study of Chronic Kidney Disease (C-STRIDE) is the first national CKD
      cohort in China. It will enroll approximately 3 000 pre-dialysis CKD patients
      aged between 18 and 74 years and follow-up for at least 5 years. Questionnaires,
      anthropometric measures, laboratory tests, and biomaterials will be collected at
      baseline and annually. The principal clinical outcomes of the C-STRIDE consist of
      renal disease events, cardiovascular events, and death. Based on the longitudinal
      clinical data and biomaterials, the risk factors with CKD progression and other
      outcomes will be analyzed, and candidate markers and predicted models will be
      established. CONCLUSION: The C-STRIDE would provide important evidence for
      underlying mechanisms of CKD progression, valuable information for clinical
      guidelines, and healthcare policies in China.

PMID- 24902679
TI  - Adipogenic and insulin resistance- promoting effects of milk consumption.

PMID- 24902683
TI  - The impact of marketing language on patient preference for robot-assisted
      surgery.
AB  - Robot-assisted surgery is gaining momentum as a new trend in minimally invasive
      surgery. With limited evidence supporting its use in place of the far less
      expensive conventional laparoscopic surgery, it has been suggested that marketing
      pressure is partly responsible for its widespread adoption. The impact of phrases
      that promote the novelty of robot-assisted surgery on patient decision making has
      not been investigated. We conducted a discrete choice experiment to elicit
      preference of partial colectomy technique for a hypothetical diagnosis of colon
      cancer. A convenience sample of 38 participants in an ambulatory general surgery
      clinic consented to participate. Each participant made 2 treatment decisions
      between robot-assisted surgery and conventional laparoscopic surgery, with robot
      assisted surgery described as "innovative" and "state-of-the-art" in one of the
      decisions (marketing frame), and by a disclosure of the uncertainty of available
      evidence in the other (evidence-based frame). The magnitude of the framing effect
      was large with 12 of 38 subjects (31.6%, P = .005) selecting robot-assisted
      surgery in the marketing frame and not the evidence-based frame. This is the
      first study to our knowledge to demonstrate that words that highlight novelty
      have an important influence on patient preference for robot-assisted surgery and
      that use of more neutral language can mitigate this effect. 

PMID- 24902684
TI  - Virtual digital defogging technology improves laparoscopic imaging quality.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of a newly
      developed digital defogging (DD) system on imaging quality in laparoscopic
      surgery. Lens fogging instantly degrades image quality and interrupts the flow of
      surgical maneuvers during laparoscopic surgery. To address this problem, we
      developed a DD system based on the dark channel prior. METHODS: Two hundred
      patients with gallstones or right colon cancer were enrolled in this study. Of
      the 100 patients who underwent laparoscopic cholecystectomy, 50 used a regular
      monitor (group A) while the other 50 used a DD monitor (group B). Of the 100
      patients who underwent laparoscopic colectomy, the regular monitor was used for
      50 (group C) and the DD monitor was used for the other 50 (group D). The clarity
      of images, the ratio of lens-cleaned time to operative time, and the subjective
      anxiety of the surgeons were evaluated for all cases. RESULTS: There were
      significant differences (P < .05) in the clarity of images between groups C (2.68
      +/- 1.19) and D (1.98 +/- 1.00) and the ratio of lens-cleaned time to operative
      time between groups C (5.22 +/- 0.89) and D (4.14 +/- 0.85). Moreover, the DD
      system significantly reduced the subjective anxiety of the surgeons (P < .001) in
      colectomy procedures, compared with the regular monitor. CONCLUSIONS: The DD
      system can export a dynamic stable image to the monitor during laparoscopic
      surgery, which can result in shorter operative time with less surgeon anxiety.

PMID- 24902686
TI  - Systematic review of cyanoacrylate embolization for refractory gastrointestinal
      fistulae: a promising therapy.
AB  - BACKGROUND: Surgical management of gastrointestinal fistulae has been reported to
      carry a 30-day morbidity rate up to 82% and a mortality rate ranging from 2% to
      4.8%; thus nonoperative alternatives are required. The aim of the present study
      was to assess the current experience on the use of cyanoacrylates in the
      management of these fistulae. METHODS: A systematic review was carried out on
      Medline, Embase, The Cochrane database, Academic Search Complete, MedicLatina,
      and SciELO for English, Spanish, and Portuguese articles dealing with refractory
      fistulae by means of cyanoacrylate embolization therapy. Publication dates were
      restricted from 1969 to present. Outcome parameters were study design, number of
      participants, etiology of the fistula, approach, material used, success rate,
      complications, and mortality. RESULTS: Electronic search yielded a total of 377
      articles. After a meticulous screening, only 14 studies dealing with
      foregut/midgut fistulae and 6 addressing hindgut fistulae were included. All the
      included articles were prospective and retrospective case series. Cumulative
      success rate was 81% (range 0% to 100%) and 3 out of 203 patients (1%) developed
      minor complications. CONCLUSION: Cyanoacrylate embolization of nearly all types
      of refractory gastrointestinal fistulae is a feasible and harmless technique.
      Prospective controlled studies are required to support the available evidence.

PMID- 24902687
TI  - Mitigating the Consequences of Anastomotic Leakage After Laparoscopic Rectal
      Cancer Resection: Is It Achievable by a Simple Method?
AB  - BACKGROUND: With regard to laparoscopic low anterior resection, anastomotic
      leakage still remains a challenge and continues to account for approximately 30%
      of postoperative deaths. This study was designed to evaluate whether the
      intracolonic and perineal drainage is associated with a decreased risk for
      anastomotic leakage after laparoscopic rectal cancer surgery without stool
      diversion. PATIENTS AND METHODS: Prospective data were collected from 337
      patients with rectal cancer who underwent laparoscopic resection without
      defunctioning stoma. RESULTS: A total of 157 patients underwent laparoscopic
      rectal resection, followed by the placement of intracolonic and perineal
      drainage, while 180 underwent laparoscopic surgery routinely. No difference in
      clinically significant leakage was observed between the intracolonic and perineal
      drainage and the control groups (3.8% vs 8.3%, P = .0874). However, reoperation
      was underwent at a significantly lower rate after the placement of intracolonic
      and perineal drainage (intracolonic and perineal drainage: 1 of 6 [16.7%] vs
      control: 14 of 15 [93.3%]; P < .01). In multivariate analysis, extraperitoneal
      tumor location and operation duration >=180 minutes were independently associated
      with anastomotic leakage. CONCLUSIONS: Significant risk factors of anastomotic
      leakage include extraperitoneal tumor location and operation duration >=180
      minutes. The placement of intracolonic and perineal drainage was not found to be
      significantly associated with anastomotic leakage, but this method could mitigate
      the clinical consequences of leakage and decrease the rate of reoperation and
      transverse colostomy after laparoscopic anterior resection for rectal cancer.

PMID- 24902685
TI  - First experience on laparoscopic near-infrared fluorescence imaging of hepatic
      uveal melanoma metastases using indocyanine green.
AB  - BACKGROUND: Uveal melanoma is the most common primary intraocular tumor in
      adults, and up to 50% of patients will develop liver metastases. Complete
      surgical resection of these metastases can improve 5-year survival, but only a
      few patients are eligible for radical surgical treatment. The aim of this study
      was to introduce a near-infrared (NIR) fluorescence laparoscope during minimally
      invasive surgery for intraoperative identification of uveal melanoma hepatic
      metastases and to use it to provide guidance during resection. METHODS: Three
      patients diagnosed with one solitary liver metastasis from uveal melanoma are
      presented. Patients received 10 mg indocyanine green (ICG) intravenously 24 hours
      before surgery. A NIR fluorescence laparoscope was used to detect malignant liver
      lesions. RESULTS: In all 3 patients, laparoscopic NIR fluorescence imaging using
      ICG successfully identified uveal melanoma metastases. In 2 patients, multiple
      additional lesions were identified by inspection and NIR fluorescence imaging,
      which were not identified by preoperative conventional imaging. In one patient,
      one additional lesion, not identified by computed tomography, magnetic resonance
      imaging, laparoscopic ultrasonography, and inspection, was observed with NIR
      fluorescence imaging only. Importantly, NIR fluorescence imaging provided
      guidance during resection of these metastases. CONCLUSIONS: We describe the
      successful use of laparoscopic identification and resection of uveal melanoma
      liver metastases using NIR fluorescence imaging and ICG. This procedure is
      minimally invasive and should be used as complementary to conventional techniques
      for the detection and resection of liver metastases.

PMID- 24902688
TI  - Feasibility and Safety of Laparoscopic Colon Surgery Performed Under Intravenous
      Sedation and Local Anesthesia Using Microinvasive (<3 mm) Instruments: An Acute
      and Survival Study on Porcine Model.
AB  - PURPOSE: The purpose of the study was to evaluate the feasibility and safety of
      performing laparoscopic intestinal surgery using local anesthesia and intravenous
      sedation with instruments <3 mm in diameter. METHODS: Porcine model with acute (n
      = 2) and the survival studies (n = 8): all female pigs, weight (median 36.4 kg,
      range 33.2-38.4 kg). Surgeries were performed using only intravenous sedation
      with ketamine-midazolam and local anesthetic infiltration at the sites of trocar
      insertion, with airway protection. CO2 pneumoperitoneum was maintained using
      pressure of 3 to 5 mm Hg. Commercially available instruments, sizes <3 mm in
      diameter were used. Surgical steps were as follows: (a) exploration of all
      quadrants of the abdomen and pelvis, (b) "running" the entire length of small
      bowel, (c) dissection of bowel attachments to the peritoneal sidewall, and (d)
      creating a 2.5 cm enterotomy in the colon and suture repair of this defect.
      RESULTS: All 10 surgeries were completed successfully. Animals tolerated the
      procedure well, with no requirement of intubation. There were no decrements in
      vital signs during pneumoperitoneum or surgery. Despite spontaneous respiration
      movements, all planned surgical maneuvers were feasible. The median length of
      operations was 74 minutes (range 56-165 minutes). All survival animals had an
      uneventful recovery; there were no infectious complications, oral intake and
      bowel function returned within 24 hours. CONCLUSIONS: It appears feasible and
      safe to perform simple laparoscopic intestinal procedures using instruments <3 mm
      in diameter and low CO2 insufflation pressure under local anesthesia and
      intravenous sedation. This methodology holds promise in the development of new
      approaches to intestinal surgery and disease diagnosis.

PMID- 24902689
TI  - An alternative low-cost illumination apparatus for surgical procedures.

PMID- 24902690
TI  - D-shape asymmetric excision of sacrococcygeal pilonidal sinus with primary
      closure, suction drain, and subcuticular skin closure: an analysis of risks
      factors for long-term recurrence.
AB  - BACKGROUND: Few studies have reported long-term recurrence rates after asymmetric
      excision with primary closure in the treatment of sacrococcygeal pilonidal
      disease. METHODS: A retrospective analysis of a prospectively maintained database
      of 550 surgical excisions performed for sacrococcygeal pilonidal disease between
      1988 and 2005 was performed. RESULTS: A total of 550 patients with a diagnosis of
      pilonidal sinus underwent surgical excision over a period of 17 years. Thirty
      eight out of the 550 patients (3.5%) were lost at follow-up. At a mean follow up
      of 11.2 +/- 5.3 years, median 11 years (range = 3-22), the recurrence rate was
      8.9%. Actuarial 1-, 5-, 10-, and 20-year disease-free survival rates were 98%,
      94%, 92%, and 83%, respectively, with a median overall disease-free survival of
      10 years (95% confidence interval [CI] = 3-15). When patients were stratified
      according to several variables known to influence recurrence, an age of less or
      >=22 years (odds ratio [OR] = 1.5, 95% CI = 0.3-7.5, P = .001), a family history
      of sinus (OR = 5.9, 95% CI = 2.7-12, P = .0001), and intraoperative methylene
      blue use (OR = 6.3, 95% CI = 1.2-31, P = .024) were indicated as independent
      predictors of disease-free survival rates. CONCLUSIONS: D-shape asymmetric
      excision and scar lateralization, with primary multilayer subcuticular closure,
      suction drain insertion, and skin closure in patients with sacrococcygeal
      pilonidal disease is a safe and adequate surgical treatment offering an effective
      healing rate as well as low recurrence. Several features are likely to predict a
      better or a worse long-term recurrence rate in patients undergoing surgery for
      sinus pilonidalis.

PMID- 24902691
TI  - Design of a test system for the development of advanced video chips and software
      algorithms.
AB  - BACKGROUND: Visual deterioration is a crucial point in minimally invasive surgery
      impeding surgical performance. Modern image processing technologies appear to be
      promising approaches for further image optimization by digital elimination of
      disturbing particles. To make them mature for clinical application, an
      experimental test environment for evaluation of possible image interferences
      would be most helpful. METHODS: After a comprehensive review of the literature
      (MEDLINE, IEEE, Google Scholar), a test bed for generation of artificial surgical
      smoke and mist was evolved. Smoke was generated by a fog machine and mist
      produced by a nebulizer. The size of resulting droplets was measured
      microscopically and compared with biological smoke (electrocautery) and mist
      (ultrasound dissection) emerging during minimally invasive surgical procedures.
      RESULTS: The particles resulting from artificial generation are in the range of
      the size of biological droplets. For surgical smoke, the droplet dimension
      produced by the fog machine was 4.19 um compared with 4.65 um generated by
      electrocautery during a surgical procedure. The size of artificial mist produced
      by the nebulizer ranged between 45.38 and 48.04 um compared with the range
      between 30.80 and 56.27 um that was generated during minimally invasive
      ultrasonic dissection. CONCLUSION: A suitable test bed for artificial smoke and
      mist generation was developed revealing almost identical droplet characteristics
      as produced during minimally invasive surgical procedures. The possibility to
      generate image interferences comparable to those occurring during laparoscopy
      (electrocautery and ultrasound dissection) provides a basis for the future
      development of image processing technologies for clinical applications.

PMID- 24902692
TI  - The use of TachoSil as sealant in an experimental model of colonic perforation.
AB  - BACKGROUND: The suture dehiscence has traditionally represented a major surgical
      problem that has not fully resolved. Surgeons should perform sutures in
      nonoptimal conditions using different methods of sealing and/or reinforcement of
      suture. The aim is to assess the effectiveness of TachoSil in an experimental
      model of colon perforations in a simulated precarious situation. METHODS: Forty
      Wistar rats of both genders (14-24 weeks old) were equally divided in 2 groups;
      study group was submitted to extended starvation and segmental ischemia. The
      surgical complications analyzed were animal death, colonic leaks, or intra
      abdominal infection, either as local abscesses or diffuse peritonitis. The burst
      pressure was measured in millimeters of mercury. The histological analysis was
      performed according to Ehrlich and Hunt numerical scale modified by Phillips.
      RESULTS: Only 1 animal belonging to the study group died as a consequence of the
      colonic ischemia. The eventual colonic leak or diffuse peritonitis was reported.
      Three local abscesses were observed in the study group and one in the control
      group, and numerous microscopic abscesses in histological analysis (12 vs. 11)
      were detected. The average burst pressure in the study group was 209.47 +/-
      50.274 versus 203 +/- 51.514 mm Hg in the control group. No differences were
      observed in any of the variables analyzed in the histological activity.
      CONCLUSION: TachoSil has proven useful as a sealant of colonic perforations in
      our experimental study. We therefore conclude that its use in situations of
      insecurity may be adequate, even in optimal conditions in which reinforcement of
      previous suture is not strictly required.

PMID- 24902693
TI  - Use of buccal mucosa grafts for urethral reconstruction in children: a
      retrospective cohort study.
AB  - BACKGROUND: The use of buccal mucosa grafts (BMG) for urethral reconstruction has
      increased in popularity over the last several decades. Our aim was to describe
      our institutional experience with and outcomes after BMG urethroplasty. METHODS:
      We conducted a retrospective cohort study of boys undergoing BMG urethral
      reconstruction. Preoperative and perioperative characteristics and postoperative
      outcomes were evaluated. RESULTS: Twenty-nine patients (median age 8.2 years)
      underwent BMG urethroplasty from 1995-2012. Of the 10 patients undergoing 1-stage
      repairs, 6 had tubularized grafts, the last of which was performed in 2000 due to
      an unacceptably high revision rate (100%). A 2-stage approach was elected for 19
      patients (median follow-up 21.3 months). Complications including stricture,
      fistula, or chordee were seen in 60% of patients completing both stages and 32%
      required >=1 revision. However, 71% of 2-stage patients were free of significant
      problems at last follow-up. CONCLUSIONS: We found BMG to be a reasonable option
      for use in complex pediatric urethral reconstruction. Tubularized grafts had poor
      results, and we no longer use them. We favor a 2-stage approach for all patients
      except those with "simple" non-hypospadiac strictures. Although revision
      procedures were not uncommon, the majority of patients were ultimately free of
      long-term problems.

PMID- 24902694
TI  - Prevalence of hypovitaminosis D and predictors of vitamin D status in Italian
      healthy adolescents.
AB  - BACKGROUND: Vitamin D plays an important role in health promotion during
      adolescence. Vitamin D deficiency and insufficiency are common in adolescents
      worldwide. Few data on vitamin D status and risk factors for hypovitaminosis D in
      Italian adolescents are currently available. METHODS: 25-hydroxyvitamin D (25-OH
      D) and parathyroid hormone (PTH) levels were evaluated in 427 Italian healthy
      adolescents (10.0-21.0 years). We used the following cut-off of 25-OH-D to define
      vitamin D status: deficiency < 50 nmol/L; insufficiency 50-75 nmol/L; sufficiency
      >= 75 nmol/L. Hypovitaminosis D was defined as 25-OH-D levels < 75.0 nmol/L and
      severe vitamin D deficiency as 25-OH-D levels < 25.0 nmol/L. We evaluated gender,
      residence, season of blood withdrawal, ethnicity, weight status, sun exposure,
      use of sunscreens, outdoor physical activity, and history of fractures as
      predictors of vitamin D status. RESULTS: Enrolled adolescents had a median serum
      25-OH-D level of 50.0 nmol/L, range 8.1-174.7, with 82.2% having hypovitaminosis
      D. Vitamin D deficiency and insufficiency were detected in 49.9% and 32.3% of
      adolescents, respectively. Among those with deficiency, 38 subjects were severely
      deficient (38/427, 8.9% of the entire sample). Non-white adolescents had a higher
      prevalence of severe vitamin D deficiency than white subjects (6/17-35.3% vs
      32/410-7.8% respectively, p = 0.002). Logistic regression showed increased risk
      of hypovitaminosis D as follows: blood withdrawal taken in winter-spring (Odds
      ratio (OR) 5.64) compared to summer-fall period; overweight-obese adolescents (OR
      3.89) compared to subjects with normal body mass index (BMI); low sun exposure
      (OR 5.94) compared to moderate-good exposure and regular use of sunscreens (OR
      5.89) compared to non regular use. Adolescents who performed < 3 hours/week of
      outdoor exercise had higher prevalence of hypovitaminosis D. Gender, residence,
      and history of fractures were not associated with vitamin D status. Serum 25-OH-D
      levels were inversely related to PTH (r = -0.387, p < 0.0001) and BMI-SDS (r = 
      0.141, p = 0.007). 44/427 (10.3%) adolescents showed secondary
      hyperparathyroidism. CONCLUSIONS: Italian adolescents have high prevalence of
      vitamin D deficiency and insufficiency. Pediatricians should tackle predictors of
      vitamin D status, favoring a healthier lifestyle and promoting supplementation in
      the groups at higher risk of hypovitaminosis D.

PMID- 24902696
TI  - Ensemble analyses improve signatures of tumour hypoxia and reveal inter-platform
      differences.
AB  - BACKGROUND: The reproducibility of transcriptomic biomarkers across datasets
      remains poor, limiting clinical application. We and others have suggested that
      this is in-part caused by differential error-structure between datasets, and
      their incomplete removal by pre-processing algorithms. METHODS: To test this
      hypothesis, we systematically assessed the effects of pre-processing on biomarker
      classification using 24 different pre-processing methods and 15 distinct
      signatures of tumour hypoxia in 10 datasets (2,143 patients). RESULTS: We confirm
      strong pre-processing effects for all datasets and signatures, and find that
      these differ between microarray versions. Importantly, exploiting different pre
      processing techniques in an ensemble technique improved classification for a
      majority of signatures. CONCLUSIONS: Assessing biomarkers using an ensemble of
      pre-processing techniques shows clear value across multiple diseases, datasets
      and biomarkers. Importantly, ensemble classification improves biomarkers with
      initially good results but does not result in spuriously improved performance for
      poor biomarkers. While further research is required, this approach has the
      potential to become a standard for transcriptomic biomarkers.

PMID- 24902697
TI  - Quantity and functionality of protein fractions in chicken breast fillets
      affected by white striping.
AB  - Recently, white striations parallel to muscle fibers direction have been observed
      on the surface of chicken breast, which could be ascribed to intensive growth
      selection. The aim of this study was to evaluate the effect of white striping on
      chemical composition with special emphasis on myofibrillar and sarcoplasmic
      protein fractions that are relevant to the processing features of chicken breast
      meat. During this study, a total of 12 pectoralis major muscles from both normal
      and white striped fillets were used to evaluate chemical composition, protein
      solubility (sarcoplasmic, myofibrillar, and total protein solubility), protein
      quantity (sarcoplasmic, myofibrillar, and stromal proteins), water holding
      capacity, and protein profile by SDS-PAGE analysis. White-striped fillets
      exhibited a higher percentage of moisture (75.4 vs. 73.8%; P < 0.01),
      intramuscular fat (2.15 vs. 0.98%; P < 0.01), and collagen (1.36 vs. 1.22%; P <
      0.01), and lower content of protein (18.7 vs. 22.8%; P < 0.01) and ash (1.14 vs.
      1.34%; P < 0.01), in comparison with normal fillets. There was a great decline in
      myofibrillar (14.0 vs. 8.7%; P < 0.01) and sarcoplasmic (3.2 vs. 2.6%; P < 0.01)
      content and solubility as well as an increase in cooking loss (33.7 vs. 27.4%; P
      < 0.05) due to white striping defects. Moreover, gel electrophoresis showed that
      the concentration of 3 myofibrillar proteins corresponding to actin (42 kDa);
      LC1, slow-twitch light chain myosin (27.5 kDa); and LC3, fast-twitch light chain
      myosin (16 kDa), and almost all sarcoplasmic proteins were lower than normal. In
      conclusion, the findings of this study revealed that chicken breast meat with
      white striping defect had different chemical composition (more fat and less
      protein) and protein quality and quantity (low content of myofibrillar proteins
      and high content of stromal proteins) with respect to normal meat. Furthermore,
      white striped fillets had lower protein functionality (higher cooking loss). All
      the former changes indicate that white striping has great impact on quality
      characteristics of chicken breast meat. 

PMID- 24902698
TI  - The use of thyme and orange essential oils blend to improve quality traits of
      marinated chicken meat.
AB  - Poultry meat contains large quantities of polyunsaturated fatty acids, which lead
      to oxidative deterioration. Plant essential oils (EO) and natural compounds, with
      antioxidant properties, may be used to alleviate this problem. Two replications
      were conducted to evaluate the effects of a mixture (1:1) of thyme and orange
      oils (EO) on the quality characteristics and the oxidative stability of chicken
      meat (breast and wing). For each replication, 24 fresh breast fillets and 24
      wings were procured from a local grocery store. The EO were added to marinade
      solution to achieve a final concentration of 0.55% sodium chloride, 0.28%
      polyphosphate, and 0.05% wt/vol of EO blend. Breasts and wings were split in 2
      different groups with homogenous pH and lightness and vacuum tumbled in 2
      treatments, a 0.5% EO and a control (CON, no EO). Each group was tested for pH,
      Commission Internationale d'Eclairage color (lightness, L*; redness, a*;
      yellowness, b*), moisture content, marinade uptake, purge loss, cook yield, and
      shear force. Susceptibility to lipid oxidation was determined on fresh and frozen
      meat by TBA reactive substance analysis (induced oxidation from 0 to 150 min at
      37 degrees C). The EO breasts had lower purge loss compared with CON meat. Breast
      did not show any color, pH, marinade uptake, cooking yield, shear force, or
      moisture differences due to treatment, although cooked EO breast was slightly
      less red than CON. The EO wings presented higher a* and b* values after
      marination and lower purge loss and shear force than CON. No differences were
      detected on wings for color, pH, marinade uptake, cooking yield, or moisture
      between EO and CON wings. Both fresh and frozen EO breasts and EO wings were less
      susceptible to the lipid oxidation during all induced oxidation times compared
      with CON breasts and wings. In conclusion, EO had a positive effect on broiler
      breast and wing lipid oxidation without negatively affecting meat quality traits.

PMID- 24902695
TI  - Ryanodine receptors: physiological function and deregulation in Alzheimer
      disease.
AB  - Perturbed Endoplasmic Reticulum (ER) calcium (Ca2+) homeostasis emerges as a
      central player in Alzheimer disease (AD). Accordingly, different studies have
      reported alterations of the expression and the function of Ryanodine Receptors
      (RyR) in human AD-affected brains, in cells expressing familial AD-linked
      mutations on the beta amyloid precursor protein (betaAPP) and presenilins (the
      catalytic core in gamma-secretase complexes cleaving the betaAPP, thereby
      generating amyloid beta (Abeta) peptides), as well as in the brain of various
      transgenic AD mice models. Data converge to suggest that RyR expression and
      function alteration are associated to AD pathogenesis through the control of: i)
      betaAPP processing and Abeta peptide production, ii) neuronal death; iii)
      synaptic function; and iv) memory and learning abilities. In this review, we
      document the network of evidences suggesting that RyR could play a complex dual
      "compensatory/protective versus pathogenic" role contributing to the setting of
      histopathological lesions and synaptic deficits that are associated with the
      disease stages. We also discuss the possible mechanisms underlying RyR expression
      and function alterations in AD. Finally, we review recent publications showing
      that drug-targeting blockade of RyR and genetic manipulation of RyR reduces Abeta
      production, stabilizes synaptic transmission, and prevents learning and memory
      deficits in various AD mouse models. Chemically-designed RyR "modulators" could
      therefore be envisioned as new therapeutic compounds able to delay or block the
      progression of AD. 

PMID- 24902699
TI  - Supplemental effect of probiotic Bacillus subtilis B2A on productivity, organ
      weight, intestinal Salmonella microflora, and breast meat quality of growing
      broiler chicks.
AB  - One-day-old Ross 308 male broiler chicks were used to investigate the additive
      effect during growth of Bacillus subtilis B2A derived from soil samples on
      productivity, organ weight, intestinal Salmonella microflora, and breast meat
      quality. Five hundred seventy-six birds (46 +/- 0.5 g) were fed 3 different
      levels of B. subtilis B2A (1.1 * 10(4), 1.0 * 10(5), and 1.0 * 10(6) cfu), in a
      basal diet based on corn-soybean meal, for 28 d. In the current study, feed
      intake and feed conversion during 1 to 28 d showed significant improvement as
      dietary B. subtilis B2A increased from 1.1 * 10(4) to 1.0 * 10(6) cfu (linear, P
      < 0.05). All blood parameters, such as white blood cells, red blood cells, and
      lymphocyte and haptoglobin concentrations, were not influenced by B. subtilis B2A
      added into the diet; however, the weights of the bursa of Fabricius were
      significantly increased linearly in B. subtilis B2A-fed groups (P < 0.05).
      Bacillus subtilis B2A supplementation was associated with reduced intestinal
      Salmonella burden (linear and quadratic, P < 0.05). Breast meat pH and color were
      not affected by B. subtilis B2A, but 1 d drip loss was decreased (linear, P <
      0.05). Our observations suggest that B. subtilis B2A benefits productivity and
      reduces Salmonella in broilers. 

PMID- 24902701
TI  - Effects of phytase supplementation on phosphorus retention in broilers and
      layers: a meta-analysis.
AB  - Phytase, a widely used feed additive in poultry diets, increases P availability
      and subsequently reduces inorganic-P supplementation and P-excretion. Phytase
      supplementation effect on P-retention in poultry has been investigated, but the
      effect sizes were highly variable. The present study's objective was to conduct
      several meta-analyses to quantitatively summarize the phytase effect on P
      retention in broilers and layers. Data from 103 and 26 controlled experiments
      testing the phytase effect on P-retention were included in 2 separate meta
      analyses for broilers and layers, respectively. The mean difference calculated by
      subtracting the means of P-retention for the control group from the phytase
      supplemented group was chosen as an effect size estimate. Between-study
      variability (heterogeneity) of mean difference was estimated using random-effect
      models and had a significant effect (P < 0.01) in both broilers and layers.
      Therefore, random-effect models were extended to mixed-effect models to explain
      heterogeneity and obtain final phytase effect size estimates. Available dietary
      and bird variables were included as fixed effects in the mixed-effect models. The
      final broiler mixed-effect model included phytase dose and Ca-to-total-P ratio
      (Ca:tP), explaining 15.6% of the heterogeneity. Other variables such as breed
      might further explain between-study variance. Broilers consuming control diets
      were associated with 48.4% P-retention. Exogenous phytase supplementation at
      1,039 FTU/kg of diet increased P-retention by 8.6 percentage units on average. A
      unit increase of phytase dose and Ca:tP from their means further increased P
      retention. For layers, the final mixed-effect models included dietary Ca, age,
      and experimental period length. The variables explained 65.9% of the
      heterogeneity. Layers receiving exogenous phytase at 371 FTU/kg were associated
      with a 5.02 percentage unit increase in P-retention. A unit increase in dietary
      Ca from its mean increased P-retention, whereas an increase in the experiment
      length and layer's age decreased P-retention. Phytase supplementation had a
      significant positive effect on P-retention in both broilers and layers, but
      effect sizes across studies were significantly heterogeneous due to differences
      in Ca contents, experiment length, bird age, and phytase dose. 

PMID- 24902700
TI  - Cytotoxic and antigenotoxic activities of phosvitin from egg yolk.
AB  - Egg yolk phosvitin is one of the most phosphorylated proteins in nature, and thus
      has a strong metal-binding ability. The objective of this study was to evaluate
      the cytotoxic and antigenotoxic activities of phosvitin in vitro. Using the 3
      [4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, the
      cytotoxicity of phosvitin was evaluated in human cancer cell lines of various
      tissue origins, including the cervix (HeLa), breast (MCF-7), stomach (AGS), lung
      (A549 and SK-MES-1), liver (HepG2), and larynx (Hep-2). The growth of all cancer
      cell lines was inhibited in a dose-dependent manner by phosvitin. Among the
      cancer cell lines tested, MCF-7 and SK-MES-1 were the least sensitive and HeLa,
      AGS, and HepG2 were the most sensitive to phosvitin. The 50% inhibition of cell
      viability values of phosvitin were 5.38, 11.57, 4.78, 6.98, 11.82, 3.93, and 9.97
      mg/mL for HeLa, MCF-7, AGS, A549, SK-MES-1, HepG2, and Hep-2, respectively. The
      protective effects of phosvitin against DNA damage in human leukocytes indicated
      that phosvitin showed protective effects against the oxidative stress-induced DNA
      damages in human leukocytes. These results suggested that phosvitin has a high
      potential to be used as an anticancer agent for humans. 

PMID- 24902703
TI  - Dietary threonine requirement of Pekin ducks from 15 to 35 days of age based on
      performance, yield, serum natural antibodies, and intestinal mucin secretion.
AB  - A study was conducted to establish the dietary Thr requirement of Pekin ducks
      from 15 to 35 d of age. Experimental diets were formulated to contain 0.55, 0.60,
      0.65, 0.75, and 0.85% Thr (0.57, 0.60, 0.64, 0.72, and 0.80% on an analyzed
      basis) and were studied in 2 experiments. In experiment 1, each diet was fed to
      10 pens of 52 drakes per pen. Samples were collected at d 35 for determinations
      of carcass yields, serum immune parameters, and intestinal characteristics.
      Experiment 2 was a digestibility study, wherein 0.5% chromic oxide was mixed into
      the experimental diets and fed from 15 to 19 d. Ileal digesta were collected at d
      19 to analyze mucin secretions and apparent ileal Thr digestibility. The results
      showed that feeding 0.72% versus 0.64% Thr improved 15 to 35 d BW gain by 55 g (P
      < 0.05), reduced feed-to-gain by 0.04 (P < 0.05), as well as increased carcass
      and breast meat yields by 22 and 24 g, respectively. Also, 0.72% Thr had the
      highest crude mucin secretion on a DM intake (DMI) basis (P < 0.05), although Thr
      had no effect on villus height, crypt depth, goblet cells, and MUC2 gene
      expression in the jejunum and ileum. In addition, serum natural IgY linearly
      increased (P < 0.0001) with dietary Thr increase. Using nonlinear regressions,
      Thr requirement was estimated to range from a low of 0.70% to maximize dry crude
      mucin secretion on a DMI basis to a high of 0.80% to maximize carcass weight and
      serum IgY production by the linear or quadratic regression. Equivalently, Thr
      requirement varied between a low of 0.62% to minimize mortality and a high of
      0.73% to maximize dry crude mucin secretion expressed as DMI using the quadratic
      broken-line model. Correspondingly, the apparent ileal digestible Thr
      requirements were estimated to be 0.52 to 0.66% (0.70 to 0.80% dietary Thr) by
      quadratic and 0.47 to 0.56% (0.62 to 0.73% dietary Thr) by quadratic broken-line
      model. 

PMID- 24902702
TI  - Effects of grinding method, particle size, and physical form of the diet on
      gastrointestinal morphology and jejunal glucose transport in laying hens.
AB  - Several studies illustrated that the structure of feed, i.e., the particle size,
      particle-size distribution, and the physical form of the diet, affects the avian
      gastrointestinal function and health leading to changes in productive
      performance. However, investigations concerning the effects of feeding
      differently processed diets on laying hens are limited and primarily concentrated
      on bird performance. The current study examines the effect of feed processing on
      the gastrointestinal morphology and on the jejunal glucose transport of laying
      hens. In 8 replicates, a total of 384 hens (Lohmann Brown) aged 20 wk were
      randomly allocated to 8 different groups and fed over a period of 21 d in a 3
      factorial design. Diets differed in 1) grinding method, either hammer or roller
      mill; 2) physical form, either mash or expandate; and 3) particle size, either
      coarsely or finely ground. During the experimental trial, the laying performance
      of each feeding group was recorded daily and the feed intake and BW determined
      weekly. After slaughtering, the weights of the pancreas, proventriculus, gizzard,
      and small intestine were measured. Villus lengths and crypt depths of the
      duodenum, jejunum, and ileum were determined. The jejunal electrogenic glucose
      transport was studied in Ussing chambers. Hens that received mash instead of
      expandate had higher proventriculus (P = 0.011), gizzard (P < 0.001), and
      pancreas (P = 0.019) weights, whereas the feeding of coarsely instead of finely
      ground diets led to higher gizzard weights (P < 0.001). Mash-fed hens showed
      longer duodenal (P < 0.001) and shorter ileal villi (P = 0.047) and increased
      duodenal villus height-to-crypt depth ratios (P < 0.001) than those given the
      expandate. Mash-fed hens had higher glucose transport rates than expandate-fed
      hens (P < 0.001). In conclusion, the feeding of coarsely ground as well as mash
      diets had stimulating effects on the development of the gastrointestinal organs.
      Moreover, the feeding of mash influenced the intestinal microstructure of the
      epithelium that was accompanied by higher glucose transport capacities. 

PMID- 24902704
TI  - Effects of Bacillus amyloliquefaciens as a probiotic strain on growth
      performance, cecal microflora, and fecal noxious gas emissions of broiler
      chickens.
AB  - This experiment was conducted to investigate the effects of Bacillus
      amyloliquefaciens probiotic (BAP) as a direct-fed microbial on growth
      performance, cecal microflora, serum immunoglobulin levels, and fecal noxious gas
      emissions of broiler chickens. A total of 400 one-day-old broiler chicks (Ross
      308) were randomly assigned to 1 of 5 treatment diets formulated to supply 0, 1,
      5, 10, and 20 g/kg of BAP and were fed for 35 d. Each treatment had 8 replicate
      pens with 10 birds per replicate. On completion of the growth trial, fecal
      samples were collected, and ammonia (NH3) and hydrogen sulfide (H2S) emissions
      were measured. Increasing concentration of BAP had positive linear effect on the
      ADG of broilers (P < 0.05) throughout the experimental period, with the highest
      values being observed in broilers offered 20 g/kg of BAP. The ADFI increased
      linearly (P < 0.02) with the inclusion of BAP during the overall experimental
      period (d 0 to 35). Providing BAP had a negative linear effect on FCR from d 0 to
      21 and d 0 to 35 (P < 0.01). Supplementation with BAP did not affect cecal
      Lactobacillus and Bacillus content, but exerted negative linear effect on cecal
      Escherichia coli (P < 0.05) with increasing the level of BAP in broiler diets.
      Additionally, BAP modified immune response of broilers by linearly increasing
      serum IgG and IgA (P < 0.01). Dietary BAP resulted in decreased fecal NH3
      emissions at 0 (linear, P < 0.001), 3, 6, 12, 24, and 48 h of incubation (linear,
      P < 0.05; quadratic, P < 0.01). Supplementation of BAP exerted negative linear
      and quadratic effects on fecal emissions of H2S (P < 0.001) throughout the
      incubation period except at 48 h, and the optimum effect was found when BAP was
      provided at 5 g/kg of diet. Based on these results, Bacillus amyloliquefaciens
      could be suggested as a potential feed additive of broiler diets. 

PMID- 24902705
TI  - Growth, serum biochemistry, complement activity, and liver gene expression
      responses of Pekin ducklings to graded levels of cultured aflatoxin B1.
AB  - A 14-d study was conducted to evaluate the effects of cultured aflatoxin B1
      (AFB1) on performance, serum biochemistry, serum natural antibody and complement
      activity, and hepatic gene expression parameters in Pekin ducklings. A total of
      144 male Pekin ducklings were weighed, tagged, and randomly allotted to 4 dietary
      treatments containing 4 concentrations of AFB1 (0, 0.11, 0.14, and 0.21 mg/kg)
      from 0 to 14 d of age (6 cages per diet; 6 ducklings per cage). Compared with the
      control group, there was a 10.9, 31.7, and 47.4% (P < 0.05) decrease in
      cumulative BW gain with 0.11, 0.14, and 0.21 mg of AFB1/kg of diet, respectively,
      but feed efficiency was not affected. Increasing concentrations of AFB1 reduced
      cumulative BW gain and feed intake both linearly and quadratically, and
      regression equations were developed with r(2) >=0.73. Feeding 0.11 to 0.21 mg of
      AFB1/kg reduced serum glucose, creatinine, albumin, total protein, globulin, Ca,
      P, and creatine phosphokinase linearly, whereas serum urea N, Cl, alkaline
      phosphatase, and aspartate amino transferase concentrations increased linearly
      with increasing AFB1 (P < 0.05). Additionally, 0.11 to 0.21 mg of AFB1/kg diets
      impaired classical and alternative complement pathways in the duckling serum when
      tested by lysis of rabbit, human type O, and horse erythrocytes, and decreased
      rabbit and horse agglutinins (P < 0.05). Liver peroxisome proliferator activated
      receptor alpha (PPARalpha) expression was linearly downregulated by AFB1 (P <
      0.01). Results from this study indicate that for every 0.10 mg/kg increase in
      dietary AFB1, cumulative feed intake and BW gain decrease approximately 230 and
      169 g per duckling from hatch to 14 d; and that AFB1 at very low concentrations
      can significantly impair liver function and gene expression, and innate immune
      dynamics in Pekin ducklings. 

PMID- 24902706
TI  - Arginine affects appetite via nitric oxide in ducks.
AB  - The objective of the study was to investigate the mechanism by which arginine
      regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d
      old male Pekin ducks were randomly allotted to 3 dietary treatments with 6
      replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn
      gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet
      containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P
      < 0.05) than the other 2 groups. In experiment 2, twenty 11-d-old ducks were
      allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were
      intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl
      (L-NAME) for 3 d, respectively. Feed intake (P < 0.07) and plasma nitric oxide
      concentration (P < 0.05) 2 h postinjection in the L-NAME administered group were
      lower than those of the control group. In conclusion, the study implied that
      arginine modifies feeding behavior possibly through controlling endogenous
      synthesis of nitric oxide in Pekin ducks. 

PMID- 24902707
TI  - Effects of dietary gossypol concentration on growth performance, blood profiles,
      and hepatic histopathology in meat ducks.
AB  - The objective of this study was to determine the effects of gossypol from
      cottonseed meal (CSM) on growth performance, blood biochemical profiles, and
      liver histopathology of ducks. A total of 900 1-d-old ducks were randomly
      allocated to 5 treatments with 12 pens/treatment and 15 ducks/pen. The 5
      experimental diets were formulated in such a way that 0% (a corn-soybean meal
      basal diet, diet 1), 25% (diet 2), 50% (diet 3), 75% (diet 4), and 100% (diet 5)
      of protein from soybean meal were replaced with that from CSM. All diets were
      formulated on a digestible amino acid basis. The experiment included 2 phases,
      the starter phase (1 to 3 wk) where the test diets contained graded levels of CSM
      and the growth phase (4 to 5 wk) where birds were fed a corn-soybean basal diet
      to examine the recovery of ducks after CSM withdrawal. Dietary CSM and gossypol
      linearly (P < 0.01) and quadratically (P < 0.01) decreased ADG and ADFI during d
      1 to 14. The threshold of daily total gossypol (TG) and free gossypol (FG) intake
      based on ADG on d 1 to 7 and d 7 to 14 were 32.20 and 2.64 mg/d, and 92.12 and
      9.62 mg/d, respectively. Serum alanine aminotransferase increased (P < 0.05)
      linearly with increasing level of gossypol in the diets (d 7), whereas aspartate
      aminotransferase increased (P < 0.05) linearly and quadratically (d 14). Serum
      albumin concentration decreased (P < 0.05) quadratically with increasing dietary
      CSM concentrations on d 21. The degree of damage to the liver increased markedly
      with increasing dietary CSM and gossypol content and the length of CSM and
      gossypol intake. On d 35, there was no difference on BW and blood profiles of
      ducks among all treatments. These results suggest that meat ducks' dietary TG and
      FG concentration should be lower than 928.9 and 77.2 mg/kg, respectively, during
      d 1 to 21 of age and that a 2-wk withdrawal of diets containing gossypol should
      be considered. 

PMID- 24902709
TI  - Neurovascular complications of ovarian hyperstimulation syndrome (OHSS): from
      pathophysiology to recent treatment options.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a severe iatrogenic complication of
      ovulation induction, which has a very serious impact on the patient's health, as
      it is often associated with a high morbidity and mortality risk. Indeed, patients
      classified as having severe OHSS presented with liquid imbalance signs (such as
      rapid weight gain, tense ascites, respiratory difficulty and progressive
      oliguria), which are related to the fluid shift from the intravascular space to
      third space compartments subsequent to an increased capillary permeability. In
      this way, cardiovascular system findings include decreased intravascular volume,
      decreased blood pressure, decreased central venous perfusion, and compensatory
      increased heart rate and cardiac output with arterial vasodilation might be found
      concomitantly. Notwithstanding that venous thromboembolic phenomena are a
      possible complication in advanced phases of OHSS, arterial ischemia involving the
      cerebral circulation is a rare but recently reported problem. The pathogenesis of
      thromboembolism in OHSS is not fully understood, even though hemoconcentration
      and blood hyperviscosity seem to play a role in developing thrombotic changes
      into both venous and arterial system. Interestingly, the presence of cardiac
      abnormalities in combination with inherited or acquired hypercoagulable state
      seems to increase the risk of cerebral infarct in these subjects, as recently
      shown by our group. This review is aimed at investigating the pathomechanism and
      the management of neurovascular complications related to OHSS, including new
      treatment options. 

PMID- 24902708
TI  - Defining the malaria burden in Nchelenge District, northern Zambia using the
      World Health Organization malaria indicators survey.
AB  - BACKGROUND: Malaria is considered as one of the major public health problems and
      among the diseases of poverty. In areas of stable and relatively high
      transmission, pregnant women and their newborn babies are among the higher risk
      groups. A multicentre trial on the safety and efficacy of several formulations of
      artemisinin-based combination therapy (ACT) during pregnancy is currently on
      going in four African countries, including Zambia, whose study site is in
      Nchelenge district. As the study outcomes may be influenced by the local malaria
      endemicity, this needs to be characterized. A cross-sectional survey to determine
      the prevalence and intensity of infection among <10 years old was carried out in
      March-April 2012 in Nchelenge district. METHODS: The sampling unit was the
      household where all children < 10 years of age were included in the survey using
      simple random household selection on a GPS coded list. A blood sample for
      determining haemoglobin concentration and identifying malaria infection was
      collected from each recruited child. RESULTS: Six hundred thirty households were
      selected and 782 children tested for malaria and anaemia. Prevalence of malaria
      infection was 30.2% (236/782), the large majority (97.9%, 231/236) being
      Plasmodium falciparum and the remaining ones (2.1%, 5/236) Plasmodium malariae.
      Anaemia, defined as haemoglobin concentration <11 g/dl, was detected in 51.2%
      (398/782) children. CONCLUSION: In Zambia, despite the reported decline in
      malaria burden, pockets of high malaria endemicity, such as Nchelenge district,
      still remain. This is a border area and significant progress can be achieved only
      by concerted efforts aimed at increasing coverage of current control
      interventions across the border.

PMID- 24902710
TI  - Reshaping maternal services in Nigeria: any need for spiritual care?
AB  - BACKGROUND: High maternal and perinatal mortalities occur from deliveries
      conducted in prayer houses in Nigeria. Although some regulatory efforts have been
      deployed to tackle this problem, less attention has been placed on the possible
      motivation for seeking prayer house intervention which could be hinged on the
      spiritual belief of patients about pregnancy and childbirth. This study therefore
      seeks to determine the perception of booked antenatal patients on spiritual care
      during pregnancy and their desire for such within hospital setting. METHOD: A
      total of 397 antenatal attendees from two tertiary health institutions in
      southwest Nigeria were sampled. A pretested questionnaire was used to obtain
      information on socio-demographic features of respondents, perception of spiritual
      care during pregnancy and childbirth; and how they desire that their spiritual
      needs are addressed. Responses were subsequently collated and analyzed. RESULTS:
      Most of the women, 301 (75.8%), believe there is a need for spiritual help during
      pregnancy and childbirth. About half (48.5%) were currently seeking for help in
      prayer/mission houses while another 8.6% still intended to. Overwhelmingly, 281
      (70.8%) felt it was needful for health professionals to consider their spiritual
      needs. Most respondents, 257 (64.7%), desired that their clergy is allowed to
      pray with them while in labour and sees such collaboration as incentive that will
      improve hospital patronage. There was association between high family income and
      desire for collaboration of healthcare providers with one's clergy (OR 1.82; CI
      1.03-3.21; p = 0.04). CONCLUSION: Our women desire spiritual care during
      pregnancy and childbirth. Its incorporation into maternal health services will
      improve hospital delivery rates.

PMID- 24902711
TI  - Greek's health, waiting for the 'deus ex machina'.
AB  - Greece from May 2010 has been following Troika's (European Commission, European
      Central Bank and International Monetary Fund) austere policies in all over the
      public finance sector. Troika's instructions which are adopted by the politicians
      resulted to depressed and weak citizens. The consequences in health care sector
      are becoming visible across the society. A big part of Greek's society is
      uninsured without any access to public health care system. The vulnerable social
      groups confront catastrophic health care expenditures and impoverishment with no
      social net protection. Greeks are paying the price of their irrational way of
      living. The current paper has gathered from the literature the early effects of
      the implementation of these policies on public health and healthcare. 

PMID- 24902712
TI  - Ignorance about teaching inhaler technique is widespread among healthcare
      professionals.

PMID- 24902713
TI  - Nanomedicine for global health.
AB  - Despite modern advances, a broad range of disorders such as cancer and infectious
      diseases continually afflict the global population. Novel therapeutics are
      continuously being explored to address these challenges. Therefore, scalable,
      effective, and safe therapies that are readily accessible to third-world
      countries are of major interest. In this article, we discuss the potential
      advantages that the nanomedicine field may harness toward successful
      implementation against some of the major diseases of our generation. 

PMID- 24902714
TI  - Three-year incidence of elevated albuminuria and associated factors in a
      population-based cohort: The Taichung Community Health Study.
AB  - BACKGROUND: early-stage elevated albuminuria can be effectively detected by a
      spot urine albumin-to-creatinine ratio (UACR). Elevated albuminuria is a key
      predictor of diabetic nephropathy, progression to chronic kidney disease (CKD) or
      end-stage renal disease (ESRD), plus risk of cardiovascular disease (CVD) and
      mortality. Understanding these detectors may prevent future renal and
      cardiovascular disease. This study estimates three-year incidence in a
      representative sample of Taiwanese metropolitan adults to explore predictors.
      METHODS: the Taichung Community Health Study (TCHS) is a representative sample of
      2359 Chinese adults aged 40 years and over living in a metropolitan city during
      2004-2005. In 2007-2009, a total of 1648 (71.3%) individuals participated in
      follow-up. This study includes only individuals with normal albumin excretion at
      baseline examination. Three-year incidence and baseline factors linked with
      elevated albuminuria were evaluated. RESULTS: about 87.0% (n = 1434) of subjects
      exhibited normal albumin excretion at baseline. Three-year age- and gender
      weighted incidence was 4.5% (95% CI: 3.4-5.6%). Multivariate logistic regression
      showed subjects with elevated waist-to-hip ratio (WHR) (OR: 2.2, 95% CI: 1.2
      3.9), abnormal creatinine (OR: 3.7, 95% CI: 1.1-12.6), hyperuricaemia (OR: 1.8,
      95% CI: 1.0-3.3) and elevated baseline UACR (OR: 4.0, 95% CI: 1.1-14.3 for UACR
      of 3.20-6.39 mg/g; OR: 16.7, 95% CI: 5.0-55.5 for UACR of 6.40-29.99 mg/g) were
      more likely to have elevated albuminuria. CONCLUSIONS: this is the first
      population-based longitudinal study to rate incidence of elevated albuminuria and
      identify associated factors in a random sample of a Chinese population. Central
      obesity, renal function, hyperuricaemia and baseline UACR are independent risk
      factors.

PMID- 24902715
TI  - Integrated approaches for analyzing U1-70K cleavage in Alzheimer's disease.
AB  - The accumulation of pathologic protein fragments is common in neurodegenerative
      disorders. We have recently identified in Alzheimer's disease (AD) the
      aggregation of the U1-70K splicing factor and abnormal RNA processing. Here, we
      present that U1-70K can be cleaved into an N-terminal truncation (N40K) in ~50%
      of AD cases, and the N40K abundance is inversely proportional to the total level
      of U1-70K. To map the cleavage site, we compared tryptic peptides of N40K and
      stable isotope labeled U1-70K by liquid chromatography-tandem mass spectrometry
      (MS), revealing that the proteolysis site is located in a highly repetitive and
      hydrophilic domain of U1-70K. We then adapted Western blotting to map the
      cleavage site in two steps: (i) mass spectrometric analysis revealing that U1-70K
      and N40K share the same N-termini and contain no major modifications; (ii)
      matching N40K with a series of six recombinant U1-70K truncations to define the
      cleavage site within a small region (Arg300 +/- 6 residues). Finally, N40K
      expression led to substantial degeneration of rat primary hippocampal neurons. In
      summary, we combined multiple approaches to identify the U1-70K proteolytic site
      and found that the N40K fragment might contribute to neuronal toxicity in
      Alzheimer's disease. 

PMID- 24902716
TI  - DEF- and GLO-like proteins may have lost most of their interaction partners
      during angiosperm evolution.
AB  - BACKGROUND AND AIMS: DEFICIENS (DEF)- and GLOBOSA (GLO)-like proteins constitute
      two sister clades of floral homeotic transcription factors that were already
      present in the most recent common ancestor (MRCA) of extant angiosperms. Together
      they specify the identity of petals and stamens in flowering plants. In core
      eudicots, DEF- and GLO-like proteins are functional in the cell only as
      heterodimers with each other. There is evidence that this obligate
      heterodimerization contributed to the canalization of the flower structure of
      core eudicots during evolution. It remains unknown as to whether this strict
      heterodimerization is an ancient feature that can be traced back to the MRCA of
      extant flowering plants or if it evolved later during the evolution of the crown
      group angiosperms. METHODS: The interactions of DEF- and GLO-like proteins of the
      early-diverging angiosperms Amborella trichopoda and Nuphar advena and of the
      magnoliid Liriodendron tulipifera were analysed by employing yeast two-hybrid
      analysis and electrophoretic mobility shift assay (EMSA). Character-state
      reconstruction, including data from other species as well, was used to infer the
      ancestral interaction patterns of DEF- and GLO-like proteins. KEY RESULTS: The
      yeast two-hybrid and EMSA data suggest that DEF- and GLO-like proteins from early
      diverging angiosperms both homo- and heterodimerize. Character-state
      reconstruction suggests that the ability to form heterodimeric complexes already
      existed in the MRCA of extant angiosperms and that this property remained highly
      conserved throughout angiosperm evolution. Homodimerization of DEF- and GLO-like
      proteins also existed in the MRCA of all extant angiosperms. DEF-like protein
      homodimerization was probably lost very early in angiosperm evolution and was not
      present in the MRCA of eudicots and monocots. GLO-like protein homodimerization
      might have been lost later during evolution, but very probably was not present in
      the MRCA of eudicots. CONCLUSIONS: The flexibility of DEF- and GLO-like protein
      interactions in early-diverging angiosperms may be one reason for the highly
      diverse flower morphologies observed in these species. The results strengthen the
      hypothesis that a reduction in the number of interaction partners of DEF- and GLO
      like proteins, with DEF-GLO heterodimers remaining the only DNA-binding dimers in
      core eudicots, contributed to developmental robustness, canalization of flower
      development and the diversification of angiosperms.

PMID- 24902717
TI  - Controlling the activation of the Bv8/prokineticin system reduces
      neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic
      animals.
AB  - BACKGROUND AND PURPOSE: Chemokines are involved in neuroinflammation and
      contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2)
      and its receptors (PKR1 and PKR2 ) have a role in inflammatory pain and
      immunomodulation. In the present study, we investigated the involvement of PROK2
      and its receptors in neuropathic pain. EXPERIMENTAL APPROACH: Effects of single,
      intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1
      week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated
      in mice with chronic constriction of the sciatic nerve (CCI). Expression and
      localization of PROK2 and of its receptors at peripheral and central level was
      evaluated 10 days after CCI, following treatment for 1 week with saline or PC1.
      IL-1beta and IL-10 levels, along with glia activation, were evaluated. KEY
      RESULTS: Subcutaneous, intrathecal and perineural PC1 acutely abolished the CCI
      induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor
      PKR2 were up-regulated in nociceptors, in Schwann cells and in activated
      astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week)
      alleviated established thermal hyperalgesia and allodynia, reduced the injury
      induced overexpression of PROK2, significantly blunted nerve injury-induced
      microgliosis and astrocyte activation in the spinal cord and restored the
      physiological levels of proinflammatory and anti-inflammatory cytokines in
      periphery and in spinal cord. CONCLUSION AND IMPLICATIONS: The prokineticin
      system contributes to pain modulation via neuron-glia interaction. Sustained
      inhibition of the prokineticin system, at peripheral or central levels, blocked
      both pain symptoms and some events underlying disease progression.

PMID- 24902718
TI  - Fate of nutrients in shallow groundwater receiving treated septage, Malibu, CA.
AB  - Treated wastewater discharged from more than 400 onsite wastewater treatment
      systems (OWTS) near the Civic Center area of Malibu, California, 40 km west of
      downtown Los Angeles, composes 28% of the recharge to a 3.4 km(2) alluvial
      aquifer. On the basis of delta(18) O and deltaD data, the fraction of wastewater
      in some samples was >70%. Ammonium and nitrate concentrations in water from 15
      water-table wells sampled in July 2009 and April 2010 ranged from <0.01 to 12
      milligrams per liter as nitrogen (mg/L as N), and from <0.01 to 11 mg/L as N,
      respectively. Chemical and isotopic data (delta(15) N of ammonium and nitrate,
      and delta(18) O of nitrate) show two processes remove nitrogen discharged from
      OWTS. Where groundwater was reducing, sorption of ammonium resulted in 30 to 50%
      nitrogen removal. Where groundwater was initially oxic, nitrification with
      subsequent denitrification as reducing conditions developed, resulted in up to
      60% nitrogen removal. Nitrogen removal through sorption dominated during the
      cooler April sample period, and denitrification dominated during the warmer July
      sample period. The combination of mixing and nitrogen removal due to
      denitrification, sorption, and volatilization produces a delta(15) N apparent
      fractionation factor (epsilonapp = -5), that can be explained using laboratory
      derived fractionation factors (epsilon) for the individual processes. Phosphate
      concentrations ranged from < 0.04 to 2 mg/L as phosphorous. Sorption to iron
      oxides on the surfaces of mineral grains at near-neutral pH's removed some
      phosphate; however, little removal occurred at more alkaline pH's (>7.3). 

PMID- 24902720
TI  - Persistent homology analysis of protein structure, flexibility, and folding.
AB  - Proteins are the most important biomolecules for living organisms. The
      understanding of protein structure, function, dynamics, and transport is one of
      the most challenging tasks in biological science. In the present work, persistent
      homology is, for the first time, introduced for extracting molecular topological
      fingerprints (MTFs) based on the persistence of molecular topological invariants.
      MTFs are utilized for protein characterization, identification, and
      classification. The method of slicing is proposed to track the geometric origin
      of protein topological invariants. Both all-atom and coarse-grained
      representations of MTFs are constructed. A new cutoff-like filtration is proposed
      to shed light on the optimal cutoff distance in elastic network models. On the
      basis of the correlation between protein compactness, rigidity, and connectivity,
      we propose an accumulated bar length generated from persistent topological
      invariants for the quantitative modeling of protein flexibility. To this end, a
      correlation matrix-based filtration is developed. This approach gives rise to an
      accurate prediction of the optimal characteristic distance used in protein B
      factor analysis. Finally, MTFs are employed to characterize protein topological
      evolution during protein folding and quantitatively predict the protein folding
      stability. An excellent consistence between our persistent homology prediction
      and molecular dynamics simulation is found. This work reveals the topology
      function relationship of proteins.

PMID- 24902721
TI  - Catechol-O-methyltransferase gene methylation and substance use in adolescents:
      the TRAILS study.
AB  - Substance use often starts in adolescence and poses a major problem for society
      and individual health. The dopamine system plays a role in substance use, and
      catechol-O-methyltransferase (COMT) is an important enzyme that degrades
      dopamine. The Val(108/158) Met polymorphism modulates COMT activity and thus
      dopamine levels, and has been linked to substance use. COMT gene methylation, on
      the other hand, may affect expression and thus indirectly COMT activity. We
      investigated whether methylation of the COMT gene was associated with
      adolescents' substance use. Furthermore, we explored whether the COMT
      Val(108/158) Met polymorphism interacts with COMT gene methylation in association
      with substance use. In 463 adolescents (mean age=16, 50.8% girls), substance use
      (cigarette smoking, alcohol and cannabis use) was assessed with self-report
      questionnaires. From blood samples, COMT Val(108/158) Met genotype and
      methylation rates of membrane bound (MB) and soluble (S) COMT promoters were
      assessed. MB-COMT promoter methylation was associated with non-daily smoking
      [odds ratio (OR)=1.82, P=0.03], but not with daily smoking (OR=1.20, P=0.34), MB
      COMT promoter methylation was not associated with alcohol use. Adolescents with
      the Met/Met genotype and high rates of MB-COMT promoter methylation were less
      likely to be high-frequent cannabis users than adolescents with the Val/Val or
      Val/Met genotype. S-COMT promoter methylation was not associated with substance
      use. These results indicate that there is an association between substance use
      and COMT gene methylation. Although this association is complex, combining
      genetic and epigenetic variation of the COMT gene may be helpful in further
      elucidating the influence of the dopamine system on substance use in adolescence.

PMID- 24902722
TI  - Defining distal femoral anatomy for rotational alignment in total knee
      arthroplasty: a magnetic resonance imaging-based study.
AB  - BACKGROUND: The rotational alignment of the femoral component in total knee
      arthroplasty (TKA) is regarded as being one of the critical factors associated
      with its long-term success. Traditionally, the femoral component is aligned
      parallel to the transepicondylar axis (TEA), perpendicular to the Whiteside's
      line (WL) or at 3 degrees external rotation to the posterior condylar line (PCL).
      The aim of this study was to use magnetic resonance imaging (MRI) to evaluate the
      relationship between these anatomical axes used for femoral component rotation
      (TEA to WL and PCL to TEA) and identify if any of these relationships were
      influenced by age, sex or coronal axial deformity (mechanical axis). METHODS: Two
      hundred and sixty-five patients undergoing preoperative MRI for patient-specific
      jigs TKA were included in our study. The MRI data were then analysed via
      preoperative planning software, and values relating to WL, TEA, PCL and coronal
      axial alignment were generated. RESULTS: The mean age was 66.0 +/- 8.7 years.
      There were 102 men and 163 women. The average mechanical axis (coronal deformity)
      was 4.2 +/- 6.1 degrees of varus. TEA compared with WL was on average 92.6 +/-
      2.3 degrees. PCL was on average 2.3 +/- 1.8 degrees internally rotated to the
      TEA. The PCL was more internally rotated in women (P < 0.01) and valgus (P <
      0.001) knees. There was no significant relationship between age or varus knees
      when comparing TEA to WL (P > 0.1) and PCL to TEA (P > 0.1). CONCLUSIONS: Our
      study shows that the previously assumed values for rotational alignment of the
      femoral component may need to be reviewed. The use of advanced preoperative
      imaging (e.g. MRI) may aid to overcome this variability and assist surgeons in
      planning femoral component alignment in TKA.

PMID- 24902723
TI  - An evaluation of synthetic and natural supravital stains for the cytological
      examination of dissociated cells in a microfluidic channel.
AB  - OBJECTIVE: Advances in biotechnology will result in paradigm shifts in both
      oncology and diagnostics. In pathology, methods such as microfluidics are being
      explored as delivery tools so that processed cells can serve dual purposes:
      conventional cytology-based diagnostics and recovery of the same cells for
      molecular assays. This wet mount-based approach to diagnosis will require
      staining of these cells by supravital dyes. This study was undertaken to
      determine the optimal supravital stain for the examination of cells in the wet
      mount preparations present in microfluidic platforms. METHODS: Cells were
      dissociated from portions of tissue similar in size to a traditional core biopsy.
      These tissue-free cells were separately examined with two synthetic dyes and two
      natural dyes at varying dilutions. RESULTS: Different dilutions of the synthetic
      dyes toluidine blue and methylene blue resulted in varying degrees of staining,
      whereas different dilutions of the natural dyes resulted in fairly constant
      intensities of colour. These characteristics affected the visualization of cells
      in wet mount preparations: optimally titered synthetic dyes gave better nuclear
      detail and cytoplasmic contrast. CONCLUSIONS: All four dyes stained the test
      cells, but to different degrees and intensities. In our assessment, optimally
      titered synthetic dyes were better suited to the wet mount approach of
      microfluidics when compared with natural dyes.

PMID- 24902724
TI  - To 'Get by' or 'get help'? A qualitative study of physicians' challenges and
      dilemmas when patients have limited English proficiency.
AB  - OBJECTIVE: Encounters between patients and physicians who do not speak the same
      language are relatively common in Canada, particularly in urban settings; this
      trend is increasing worldwide. Language discordance has important effects on
      health outcomes, including mortality. This study sought to explore physicians'
      experiences of care provision in situations of language discordance in depth.
      DESIGN: Qualitative study based on individual interviews. Interview guides
      elicited physicians' perspectives on how they determined whether communication
      could proceed unaided. A descriptive qualitative approach was adopted, entailing
      inductive thematic analysis. PARTICIPANTS: 22 physicians experienced in treating
      patients in situations of language discordance were recruited from the emergency
      and internal medicine departments of an urban tertiary-care hospital. SETTING:
      Large, inner-city teaching hospital in Toronto, Canada, one of the most
      linguistically diverse cities internationally. RESULTS: Determining when to 'get
      by' or 'get help' in order to facilitate communication was described as a fluid
      and variable process. Deciding which strategy to use depended on three inter
      related factors: time/time constraints, acuity of situation and ease of
      use/availability of translation aids. Participants reported at times feeling
      conflicted about their decisions, portraying some of these clinical encounters as
      a 'troubling space' in which they experienced one or more dilemmas related to
      real versus ideal practice, responsibility and informed consent. CONCLUSIONS: In
      situations of language discordance, a physician's decision to 'get by' (vs 'get
      help') rests on a judgement of whether communication can be considered 'good
      enough' to proceed and depends on the circumstances of the specific encounter.
      The tension set up between what is 'ideal' and what is practically possible can
      be experienced as a dilemma by physicians. The study's findings have implications
      for practice and policy not only in Canada but in other multilingual settings,
      and indicate that physicians require greater support.

PMID- 24902725
TI  - Comparison of the aetiology of stillbirth over five decades in a single centre: a
      retrospective study.
AB  - OBJECTIVE: To compare the rates and aetiologies of stillbirth over the past 50
      years. STUDY DESIGN: We reviewed all autopsy reports for stillbirths occurring
      between 1989 and 2009 at the McGill University Health Centre to determine the
      pathological aetiology of stillbirths. We also reviewed maternal characteristics.
      We compared our results with a previous study published in 1992 on aetiologies of
      stillbirth from 1961 to 1988 at the same institution. RESULTS: From among the 79
      410 births between 1989 and 2009, 217 stillbirths were included in our study. The
      mean maternal age was 31.05 (+/-5.8) years. In 28.1% of cases, there was a
      history of subfertility. The mean gestational age at diagnosis was 32.69 (+/
      5.58) weeks, with a birthweight of 1888 (+/-1084) g. The main causes of
      stillbirth were unknown (26.7%), placental factors (19.8%) and abruptio placentae
      (12.9%). Other causes included haematogenous or ascending infection (10.6%),
      fetal malformations (8.3%), maternal hypertension (3.2%), intrauterine growth
      restriction (2.8%), diabetes (1.8%) and intrapartum asphyxia (1.4%). Other fetal
      causes were found in 12.4% of cases. CONCLUSIONS: Owing to detailed pathological
      examination of most stillbirth cases over the past five decades at our tertiary
      obstetrical centre, we could study the trends in the aetiology of stillbirths in
      a cohort of more than 150 000 births. In 50 years, the rate of stillbirth has
      decreased from 115 to 32 cases/10 000 births from the 1960s to 2000s, which
      represents a reduction of 72%. Stillbirth from unknown cause remains the most
      common contributor, with 40% of these cases occurring in late pregnancy.

PMID- 24902727
TI  - Unexpectedly long hospital stays as an indicator of risk of unsafe care: an
      exploratory study.
AB  - OBJECTIVES: We developed an outcome indicator based on the finding that
      complications often prolong the patient's hospital stay. A higher percentage of
      patients with an unexpectedly long length of stay (UL-LOS) compared to the
      national average may indicate shortcomings in patient safety. We explored the
      utility of the UL-LOS indicator. SETTING: We used data of 61 Dutch hospitals. In
      total these hospitals had 1 400 000 clinical discharges in 2011. PARTICIPANTS:
      The indicator is based on the percentage of patients with a prolonged length of
      stay of more than 50% of the expected length of stay and calculated among
      survivors. INTERVENTIONS: No interventions were made. OUTCOME MEASURES: The
      outcome measures were the variability of the indicator across hospitals, the
      stability over time, the correlation between the UL-LOS and standardised
      mortality and the influence on the indicator of hospitals that did have problems
      discharging their patients to other health services such as nursing homes.
      RESULTS: In order to compare hospitals properly the expected length of stay was
      computed based on comparison with benchmark populations. The standardisation was
      based on patients' age, primary diagnosis and main procedure. The UL-LOS
      indicator showed considerable variability between the Dutch hospitals: from 8.6%
      to 20.1% in 2011. The outcomes had relatively small CIs since they were based on
      large numbers of patients. The stability of the indicator over time was quite
      high. The indicator had a significant positive correlation with the standardised
      mortality (r=0.44 (p<0.001)), and no significant correlation with the percentage
      of patients that was discharged to other facilities than other hospitals and home
      (r=-0.15 (p>0.05)). CONCLUSIONS: The UL-LOS indicator is a useful addition to
      other patient safety indicators by revealing variation between hospitals and
      areas of possible patient safety improvement.

PMID- 24902728
TI  - Coproduction in commissioning decisions: is there an association with decision
      satisfaction for commissioners working in the NHS? A cross-sectional survey
      2010/2011.
AB  - OBJECTIVES: To undertake an assessment of the association between coproduction
      and satisfaction with decisions made for local healthcare communities. DESIGN: A
      coproduction scale was developed and tested to measure individual National Health
      Service (NHS) commissioners' satisfaction with commissioning decisions. SETTING:
      11 English Primary Care Trusts in 2010-2011. PARTICIPANTS: Staff employed at NHS
      band 7 or above involved in commissioning decisions in the NHS. 345/440 (78%) of
      participants completed part of all of the survey. MAIN OUTCOME MEASURE:
      Reliability and validity of a coproduction scale were assessed using a
      correlation-based principal component analysis model with direct oblimin
      rotation. Multilevel modelling was used to predict decision satisfaction.
      RESULTS: The analysis revealed that coproduction consisted of three principal
      components: productive discussion, information and dealing with uncertainty.
      Higher decision satisfaction was associated with smaller decisions, more
      productive discussion, decisions where information was readily available to use
      and those where decision-making tools were more often used. CONCLUSIONS: The
      research indicated that coproduction may be an important factor for satisfaction
      with decision-making in the commissioning of healthcare services.

PMID- 24902726
TI  - Predictors of injury mortality: findings from a large national cohort in
      Thailand.
AB  - OBJECTIVE: To present predictors of injury mortality by types of injury and by
      pre-existing attributes or other individual exposures identified at baseline.
      DESIGN: 5-year prospective longitudinal study. SETTING: Contemporary Thailand
      (2005-2010), a country undergoing epidemiological transition. PARTICIPANTS: Data
      derived from a research cohort of 87 037 distance-learning students enrolled at
      Sukhothai Thammathirat Open University residing nationwide. MEASURES: Cohort
      members completed a comprehensive baseline mail-out questionnaire in 2005
      reporting geodemographic, behavioural, health and injury data. These responses
      were matched with national death records using the Thai Citizen ID number. Age
      sex adjusted multinomial logistic regression was used to calculate ORs linking
      exposure variables collected at baseline to injury deaths over the next 5 years.
      RESULTS: Statistically significant predictors of injury mortality were being male
      (adjustedOR 3.87, 95% CI 2.39 to 6.26), residing in the southern areas (AOR 1.71,
      95% CI 1.05 to 2.79), being a current smoker (1.56, 95% CI 1.03 to 2.37), history
      of drunk driving (AOR 1.49, 95% CI 1.01 to 2.20) and ever having been diagnosed
      for depression (AOR 1.91, 95% CI 1.00 to 3.69). Other covariates such as being
      young, having low social support and reporting road injury in the past year at
      baseline had moderately predictive AORs ranging from 1.4 to 1.6 but were not
      statistically significant. CONCLUSIONS: We complemented national death
      registration with longitudinal data on individual, social and health attributes.
      This information is invaluable in yielding insight into certain risk traits such
      as being a young male, history of drunk driving and history of depression. Such
      information could be used to inform injury prevention policies and strategies.

PMID- 24902729
TI  - Validation of risk assessment scales and predictors of intentions to quit smoking
      in Australian Aboriginal and Torres Strait Islander peoples: a cross-sectional
      survey protocol.
AB  - INTRODUCTION: Tobacco smoking is a very significant behavioural risk factor for
      the health of Australian Aboriginal and Torres Strait Islanders, and is embedded
      as a social norm. With a focus on women of childbearing age, and men of similar
      age, this project aims to determine how Aboriginal and Torres Strait Islander
      smokers assess smoking risks and how these assessments contribute to their
      intentions to quit. The findings from this pragmatic study should contribute to
      developing culturally targeted interventions. METHODS AND ANALYSIS: A cross
      sectional study using quantitative and qualitative data. A total of 120
      Aboriginal and Torres Strait Islander community members aged 18-45 years will be
      recruited at community events and through an Aboriginal Community Controlled
      Health Service (ACCHS). Participants will be interviewed using a tablet computer
      or paper survey. The survey instrument uses modified risk behaviour scales, that
      is, the Risk Behaviour Diagnosis (RBD) scale and the Smoking Risk Assessment
      Target (SRAT) (adapted from the Risk Acceptance Ladder) to determine whether
      attitudes of Aboriginal and Torres Strait Islander smokers to health risk
      messages are predictors of intentions to quit smoking. The questionnaire will be
      assessed for face and content validity with a panel of Indigenous community
      members. The internal consistency of the RBD subscales and their patterns of
      correlation will be explored. Multivariate analyses will examine predictors of
      intentions to quit. This will include demographics such as age, gender, nicotine
      dependence, household smoking rules and perceived threat from smoking and
      efficacy for quitting. The two risk-assessment scales will be examined to see
      whether participant responses are correlated. ETHICS AND DISSEMINATION: The
      Aboriginal Health & Medical Research Council Ethics Committee and university
      ethics committees approved the study. The results will be published in a peer
      reviewed journal and a community report will be disseminated by the ACCHS, and at
      community forums. NOTE ABOUT TERMINOLOGY: We use the term Aboriginal and Torres
      Strait Islander peoples, except where previous research has reported findings
      from only one group for example, Aboriginal people. Indigenous is used here to
      refer to Indigenous peoples in the international context, and issues, policies or
      systems, for example, Indigenous health, Indigenous tobacco control.

PMID- 24902730
TI  - Work stress, work motivation and their effects on job satisfaction in community
      health workers: a cross-sectional survey in China.
AB  - OBJECTIVE: It is well documented that both work stress and work motivation are
      key determinants of job satisfaction. The aim of this study was to examine levels
      of work stress and motivation and their contribution to job satisfaction among
      community health workers in Heilongjiang Province, China. DESIGN: Cross-sectional
      survey. SETTING: Heilongjiang Province, China. PARTICIPANTS: The participants
      were 930 community health workers from six cities in Heilongjiang Province.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Multistage sampling procedures were used
      to measure socioeconomic and demographic status, work stress, work motivation and
      job satisfaction. Logistic regression analysis was performed to assess key
      determinants of job satisfaction. RESULTS: There were significant differences in
      some subscales of work stress and work motivation by some of the socioeconomic
      characteristics. Levels of overall stress perception and scores on all five work
      stress subscales were higher in dissatisfied workers relative to satisfied
      workers. However, levels of overall motivation perception and scores on the
      career development, responsibility and recognition motivation subscales were
      higher in satisfied respondents relative to dissatisfied respondents. The main
      determinants of job satisfaction were occupation; age; title; income; the career
      development, and wages and benefits subscales of work stress; and the
      recognition, responsibility and financial subscales of work motivation.
      CONCLUSIONS: The findings indicated considerable room for improvement in job
      satisfaction among community health workers in Heilongjiang Province in China.
      Healthcare managers and policymakers should take both work stress and motivation
      into consideration, as two subscales of work stress and one subscale of work
      motivation negatively influenced job satisfaction and two subscales of work
      motivation positively influenced job satisfaction.

PMID- 24902731
TI  - Non-pharmacological treatments for adult patients with functional constipation: a
      systematic review protocol.
AB  - INTRODUCTION: The aim of this review is to assess the effectiveness, efficacy and
      safety of non-pharmacological therapies for patients with functional
      constipation. METHODS AND ANALYSIS: We will electronically search OVID MEDLINE,
      EMBASE, Cochrane library, CINAHL, AMED and ISI web of knowledge without any
      language restrictions. We will also try to obtain literatures from other sources,
      such as a hand search of library journals or conference abstracts. After
      searching and screening of the studies, we will run a meta-analysis of the
      included randomised-controlled trials. We will summarise the results as risk
      ratio for dichotomous data and standardised or weighted mean difference for
      continuous data. DISSEMINATION: This systematic review will summarise current
      evidence for using non-pharmacological therapies to treat functional
      constipation, and will be disseminated through peer-review publications or
      conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO 2014:
      CRD42014006686.

PMID- 24902732
TI  - Physical activity, diet and BMI in children aged 6-8 years: a cross-sectional
      analysis.
AB  - OBJECTIVE: To assess relationships between current physical activity (PA),
      dietary intake and body mass index (BMI) in English children. DESIGN AND SETTING:
      Longitudinal birth cohort study in northeast England, cross-sectional analysis.
      PARTICIPANTS: 425 children (41% of the original cohort) aged 6-8 years (49%
      boys). MAIN OUTCOME MEASURES: PA over 7 days was measured objectively by an
      accelerometer; three categories of PA were created: 'active' >=60 min/day
      moderate-to-vigorous-intensity PA (MVPA); 'moderately active' 30-59 min/day MVPA;
      'inactive' <30 min/day MVPA. Dietary intake over 4 days was measured using a
      prospective dietary assessment tool which incorporated elements of the food diary
      and food frequency methods. Three diet categories were created: 'healthy',
      'unhealthy' and 'mixed', according to the number of portions of different foods
      consumed. Adherence to the '5-a-day' recommendations for portions of fruit and
      vegetables was also assessed. Children were classified as 'healthy weight' or
      'overweight or obese' (OW/OB) according to International Obesity Taskforce
      cutpoints for BMI. Associations between weight status and PA/diet categories were
      analysed using logistic regression. RESULTS: Few children met the UK-recommended
      guidelines for either MVPA or fruit and vegetable intake, with just 7% meeting
      the recommended amount of MVPA of 60 min/day, and 3% meeting the 5-a-day fruit
      and vegetable recommendation. Higher PA was associated with a lower OR for OW/OB
      in boys only (0.20, 95% CI 0.04 to 0.88). There was no association detected
      between dietary intake and OW/OB in either sex. CONCLUSIONS: Increasing MVPA may
      help to reduce OW/OB in boys; however, more research is required to examine this
      relationship in girls. Children are not meeting the UK guidelines for diet and
      PA, and more needs to be done to improve this situation.

PMID- 24902733
TI  - Use of corticosteroids during pregnancy and risk of asthma in offspring: a
      nationwide Danish cohort study.
AB  - OBJECTIVE: To examine whether in utero exposure to local and systemic
      corticosteroids is associated with asthma development in offspring. DESIGN:
      Cohort study. SETTING: Denmark. PARTICIPANTS: We included all singletons born
      alive in Denmark between 1996 and 2009. Data on maternal corticosteroid use,
      asthma in offspring and covariates were obtained from medical registries. MAIN
      OUTCOME MEASURES: We compared asthma risks of children prenatally exposed to
      corticosteroids and of children of former corticosteroid users with that of
      unexposed children. We computed absolute risks and used proportional-hazards
      regression to compute adjusted HRs (aHRs). Using logistic regression we compared
      exposed children with unexposed siblings in a 'within-mother-between-pregnancy'
      analysis. Adjustment addressed varying length of follow-up. RESULTS: We
      identified 877 778 children, 3.6% of whom were prenatally exposed to systemic
      (n=5327) or local (n=24 436) corticosteroids. A total of 105 677 children
      developed asthma during follow-up with a 10-year risk of 18.4% among the exposed
      and 13.5% among the unexposed. The aHR was 1.54 (95% CI 1.45 to 1.65) for
      systemic use, 1.45 (95% CI 1.40 to 1.50) for local use and 1.32 (95% CI 1.30 to
      1.34) for former use. The adjusted OR of the 'within-mother-between-pregnancy'
      analysis was 1.11 (95% CI 0.98 to 1.25). CONCLUSIONS: These population-based data
      do not support a strong causal association between maternal corticosteroid use
      during pregnancy and increased asthma risk in offspring.

PMID- 24902734
TI  - Impact of comorbidity on risk of venous thromboembolism in patients with breast
      cancer: a Danish population-based cohort study.
AB  - OBJECTIVES: To assess the interaction between comorbidity and breast cancer (BC)
      on the rate of venous thromboembolism (VTE) beyond what can be explained by the
      independent effects of BC and comorbidity. DESIGN: Population-based matched
      cohort study. SETTING: Denmark. PARTICIPANTS: Danish patients with BC (n=62 376)
      diagnosed in 1995-2010 and a comparison cohort of women without BC (n=304 803)
      from the general population were matched to the patients with BC on year of birth
      in 5-year intervals and on the specific diseases included in the Charlson
      Comorbidity Index (CCI) and atrial fibrillation and obesity. MEASURES: The rate
      ratios of VTE per 1000 person-years (PY) were computed by comorbidity levels
      using the CCI, and interaction contrasts (IC) were calculated as a measure of the
      excess or deficit VTE rate not explained by the independent effects of BC and
      comorbidity. RESULTS: Among patients with BC with a CCI score of 1, the 0-1 year
      VTE rate was 12/1000 PY, and interaction accounted for 10% of the rate (IC=3.2,
      95% CI 0.5 to 5.9). Among patients with BC with CCI >=4, the VTE rate was 17, and
      interaction accounted for 8% of the rate (IC=1.2, 95% CI -1.8 to 4.2). There was
      no interaction during 2-5 years of follow-up. CONCLUSIONS: There was only little
      interaction between BC and the CCI score on the rate of VTE.

PMID- 24902735
TI  - Patients' experiences of acupuncture and counselling for depression and comorbid
      pain: a qualitative study nested within a randomised controlled trial.
AB  - INTRODUCTION: Depression and pain frequently occur together and impact on
      outcomes of existing treatment for depression. Additional treatment options are
      required. This study aimed to explore patients' experiences of depression, the
      processes of change within acupuncture and counselling, and the elements that
      contributed to longer-term change. METHODS: In a substudy nested within a
      randomised controlled trial of acupuncture or counselling compared with usual
      care alone for depression, semistructured interviews of 52 purposively sampled
      participants were conducted and analysed using thematic analysis. RESULTS:
      Differences were reported by participants regarding their experience of
      depression with comorbid pain compared with depression alone. Along with physical
      symptoms often related to fatigue and sleep, participants with depression and
      comorbid pain generally had fewer internal and external resources available to
      manage their depression effectively. Those who had physical symptoms and were
      receiving acupuncture commonly reported that these were addressed as part of the
      treatment. For those receiving counselling, there was less emphasis on physical
      symptoms and more on help with gaining an understanding of themselves and their
      situation. Over the course of treatment, most participants in both groups
      reported receiving support to cope with depression and pain independently of
      treatment, with a focus on relevant lifestyle and behaviour changes. The
      establishment of a therapeutic relationship and their active engagement as
      participants were identified as important components of treatment. CONCLUSIONS:
      Participants with and without comorbid pain received acupuncture or counselling
      for depression, and reported specific identifiable treatment effects. The
      therapeutic relationship and participants' active engagement in recovery may play
      distinct roles in driving long-term change. Patients who present with depression
      and physical symptoms of care may wish to consider a short course of acupuncture
      to relieve symptoms prior to a referral for counselling if needed. TRIAL
      REGISTRATION NUMBER: ISRCTN63787732.

PMID- 24902737
TI  - STAP dance.

PMID- 24902736
TI  - Parental perceptions of school-based influenza immunisation in Ontario, Canada: a
      qualitative study.
AB  - OBJECTIVE: To understand the perspectives of Ontario parents regarding the
      advantages and disadvantages of adding influenza immunisation to the currently
      existing Ontario school-based immunisation programmes. DESIGN: Descriptive
      qualitative study. PARTICIPANTS: Parents of school-age children in Ontario,
      Canada, who were recruited using a variety of electronic strategies (social
      media, emails and media releases), and identified as eligible (Ontario resident,
      parent of one or more school-age children, able to read/write English) on the
      basis of a screening questionnaire. We used stratified purposeful sampling to
      obtain maximum variation in two groups: parents who had ever immunised at least
      one child against influenza or who had never done so. We conducted focus groups
      (teleconference or internet forum) and individual interviews to collect data.
      Thematic analysis was used to analyse the data. SETTING: Ontario, Canada.
      RESULTS: Of the 55 participants, 16 took part in four teleconference focus
      groups, 35 in 6 internet forum focus groups and four in individual interviews
      conducted between October 2012 and February 2013. Participants who stated that a
      school-based influenza immunisation programme would be worthwhile for their child
      valued its convenience and its potential to reduce influenza transmission without
      interfering with the family routine. However, most thought that for a programme
      to be acceptable, it would need to be well designed and voluntary, with adequate
      parental control and transparent communication between the key stakeholder groups
      of public health, schools and parents. CONCLUSIONS: These results will benefit
      decision-makers in the public health and education sectors as they consider the
      advantages and disadvantages of immunising children in schools as part of a
      system-wide influenza prevention approach. Further research is needed to assess
      the perceptions of school board and public health stakeholders.

PMID- 24902738
TI  - The SNARE protein vti1a functions in dense-core vesicle biogenesis.
AB  - The SNARE protein vti1a is proposed to drive fusion of intracellular organelles,
      but recent data also implicated vti1a in exocytosis. Here we show that vti1a is
      absent from mature secretory vesicles in adrenal chromaffin cells, but localizes
      to a compartment near the trans-Golgi network, partially overlapping with
      syntaxin-6. Exocytosis is impaired in vti1a null cells, partly due to fewer
      Ca(2+)-channels at the plasma membrane, partly due to fewer vesicles of reduced
      size and synaptobrevin-2 content. In contrast, release kinetics and Ca(2+)
      sensitivity remain unchanged, indicating that the final fusion reaction leading
      to transmitter release is unperturbed. Additional deletion of the closest related
      SNARE, vti1b, does not exacerbate the vti1a phenotype, and vti1b null cells show
      no secretion defects, indicating that vti1b does not participate in exocytosis.
      Long-term re-expression of vti1a (days) was necessary for restoration of
      secretory capacity, whereas strong short-term expression (hours) was ineffective,
      consistent with vti1a involvement in an upstream step related to vesicle
      generation, rather than in fusion. We conclude that vti1a functions in vesicle
      generation and Ca(2+)-channel trafficking, but is dispensable for transmitter
      release. 

PMID- 24902739
TI  - Elevated pulmonary artery systolic pressure predicts heart failure admissions in
      African Americans: Jackson Heart Study.
AB  - BACKGROUND: Although elevated pulmonary artery systolic pressure (PASP) is
      associated with heart failure (HF), whether PASP measurement can help predict
      future HF admissions is not known, especially in African Americans who are at
      increased risk for HF. We hypothesized that elevated PASP is associated with
      increased risk of HF admission and improves HF prediction in African American
      population. METHODS AND RESULTS: We conducted a longitudinal analysis using the
      Jackson Heart Study cohort (n=3125; 32.2% men) with baseline echocardiography
      derived PASP and follow-up for HF admissions. Hazard ratio for HF admission was
      estimated using Cox proportional hazard model adjusted for variables in the
      Atherosclerosis Risk in Community (ARIC) HF prediction model. During a median
      follow-up of 3.46 years, 3.42% of the cohort was admitted for HF. Subjects with
      HF had a higher PASP (35.6+/-11.4 versus 27.6+/-6.9 mm Hg; P<0.001). The hazard
      of HF admission increased with higher baseline PASP (adjusted hazard ratio per 10
      mm Hg increase in PASP: 2.03; 95% confidence interval, 1.67-2.48; adjusted hazard
      ratio for highest [>=33 mm Hg] versus lowest quartile [<24 mm Hg] of PASP: 2.69;
      95% confidence interval, 1.43-5.06) and remained significant irrespective of
      history of HF or preserved/reduced ejection fraction. Addition of PASP to the
      ARIC model resulted in a significant improvement in model discrimination (area
      under the curve=0.82 before versus 0.84 after; P=0.03) and improved net
      reclassification index (11-15%) using PASP as a continuous or dichotomous
      (cutoff=33 mm Hg) variable. CONCLUSIONS: Elevated PASP predicts HF admissions in
      African Americans and may aid in early identification of at-risk subjects for
      aggressive risk factor modification.

PMID- 24902741
TI  - Metabolic incentives for dishonest signals of strength in the fiddler crab Uca
      vomeris.
AB  - To reduce the potential costs of combat, animals may rely upon signals to resolve
      territorial disputes. Signals also provide a means for individuals to appear
      better than they actually are, deceiving opponents and gaining access to
      resources that would otherwise be unattainable. However, other than resource
      gains, incentives for dishonest signalling remain unexplored. In this study, we
      tested the idea that unreliable signallers pay lower metabolic costs for their
      signals, and that energetic savings could represent an incentive for cheating. We
      focused on two-toned fiddler crabs (Uca vomeris), a species that frequently uses
      its enlarged claws as signals of dominance to opponents. Previously, we found
      that regenerated U. vomeris claws are often large but weak (i.e. unreliable).
      Here, we found that the original claws of male U. vomeris consumed 43% more
      oxygen than weaker, regenerated claws, suggesting that muscle quantity drives
      variation in metabolic costs. Therefore, it seems that metabolic savings could
      provide a powerful incentive for dishonesty within fiddler crabs. 

PMID- 24902743
TI  - Net cardiac shunts in anuran amphibians: physiology or physics?
AB  - Amphibians have a single ventricle and common conus arteriosus that produces an
      equal pressure to the parallel pulmocutaneous and systemic vascular circuits. The
      distribution of blood flows between the pulmocutaneous (Qpul) and systemic (Qsys)
      circuits (net cardiac shunt) varies with a number of environmental conditions and
      behaviours; although autonomic regulation of pulmonary vascular resistance
      conductance has been emphasized, little attention has been paid to the possible
      contribution of the passive physical characteristics of the two circuits to
      pressure changes associated with variation in cardiac output. In this study, we
      re-analysed three recent studies that recorded net cardiac shunts in the cane
      toad (Rhinella marina) under a variety of conditions and treatments. In all three
      studies, Qpul and Qsys were linearly related to cardiac output (Qtot), but the
      slope was threefold higher for Qpul compared with Qsys as predicted by relative
      conductance increases associated with increases in pressure from perfused
      preparations where autonomic regulation and humoral control were eliminated. Our
      analysis indicates that the net cardiac shunt in the cane toad is predicted
      primarily by the physical, rather than physiological, characteristics of the
      parallel pulmonary and systemic vascular circuits.

PMID- 24902744
TI  - The relative roles of vision and chemosensation in mate recognition of Drosophila
      melanogaster.
AB  - Animals rely on sensory cues to classify objects in their environment and respond
      appropriately. However, the spatial structure of those sensory cues can greatly
      impact when, where and how they are perceived. In this study, we examined the
      relative roles of visual and chemosensory cues in the mate recognition behavior
      of fruit flies (Drosophila melanogaster) using a robotic fly dummy that was
      programmed to interact with individual males. By pairing male flies with dummies
      of various shapes, sizes and speeds, or coated with different pheromones, we
      determined that visual and chemical cues play specific roles at different points
      in the courtship sequence. Vision is essential for determining whether to
      approach a moving object and initiate courtship, and males were more likely to
      begin chasing objects with the same approximate dimensions as another fly.
      However, whereas males were less likely to begin chasing larger dummies, once
      started, they would continue chasing for a similar length of time regardless of
      the dummy's shape. The presence of female pheromones on the moving dummy did not
      affect the probability that males would initiate a chase, but did influence how
      long they would continue chasing. Male pheromone both inhibits chase initiation
      and shortens chase duration. Collectively, these results suggest that male D.
      melanogaster use different sensory cues to progress through the courtship
      sequence: visual cues are dominant when deciding whether to approach an object
      whereas chemosensory cues determine how long the male pursues its target.

PMID- 24902742
TI  - High fatty acid oxidation capacity and phosphorylation control despite elevated
      leak and reduced respiratory capacity in northern elephant seal muscle
      mitochondria.
AB  - Northern elephant seals (Mirounga angustirostris) are extreme, hypoxia-adapted
      endotherms that rely largely on aerobic metabolism during extended breath-hold
      dives in near-freezing water temperatures. While many aspects of their physiology
      have been characterized to account for these remarkable feats, the contribution
      of adaptations in the aerobic powerhouses of muscle cells, the mitochondria, are
      unknown. In the present study, the ontogeny and comparative physiology of
      elephant seal muscle mitochondrial respiratory function was investigated under a
      variety of substrate conditions and respiratory states. Intact mitochondrial
      networks were studied by high-resolution respirometry in saponin-permeabilized
      fiber bundles obtained from primary swimming muscles of pup, juvenile and adult
      seals, and compared with fibers from adult human vastus lateralis. Results
      indicate that seal muscle maintains a high capacity for fatty acid oxidation
      despite a progressive decrease in total respiratory capacity as animals mature
      from pups to adults. This is explained by a progressive increase in
      phosphorylation control and fatty acid utilization over pyruvate in adult seals
      compared with humans and seal pups. Interestingly, despite higher indices of
      oxidative phosphorylation efficiency, juvenile and adult seals also exhibit a
      ~50% greater capacity for respiratory 'leak' compared with humans and seal pups.
      The ontogeny of this phenotype suggests it is an adaptation of muscle to the
      prolonged breath-hold exercise and highly variable ambient temperatures
      experienced by mature elephant seals. These studies highlight the remarkable
      plasticity of mammalian mitochondria to meet the demands for both efficient ATP
      production and endothermy in a cold, oxygen-limited environment. 

PMID- 24902740
TI  - A bioengineered hydrogel system enables targeted and sustained intramyocardial
      delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing
      ventricular function in a murine model of ischemic cardiomyopathy.
AB  - BACKGROUND: Neuregulin-1beta (NRG) is a member of the epidermal growth factor
      family possessing a critical role in cardiomyocyte development and proliferation.
      Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal
      models, leading to clinical trials using daily NRG infusions. This approach is
      hindered by requiring daily infusions and off-target exposure. Therefore, this
      study aimed to encapsulate NRG in a hydrogel to be directly delivered to the
      myocardium, accomplishing sustained localized NRG delivery. METHODS AND RESULTS:
      NRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA
      in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were
      stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for
      proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and
      phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo
      studies, 2-month-old mice (n=60) underwent left anterior descending coronary
      artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG
      HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along
      with decreased caspase-3 activity compared with all controls. NRG was detected in
      myocardium 6 days after injection without evidence of off-target exposure in NRG
      HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular
      ejection fraction, decreased left ventricular area, and augmented borderzone
      thickness. CONCLUSIONS: Targeted and sustained delivery of NRG directly to the
      myocardial borderzone augments cardiomyocyte mitotic activity, decreases
      apoptosis, and greatly enhances left ventricular function in a model of ischemic
      cardiomyopathy. This novel approach to NRG administration avoids off-target
      exposure and represents a clinically translatable strategy in myocardial
      regenerative therapeutics.

PMID- 24902745
TI  - Echolocation behaviour of the big brown bat (Eptesicus fuscus) in an obstacle
      avoidance task of increasing difficulty.
AB  - Four big brown bats (Eptesicus fuscus) were challenged in an obstacle avoidance
      experiment to localize vertically stretched wires requiring progressively greater
      accuracy by diminishing the wire-to-wire distance from 50 to 10 cm. The
      performance of the bats decreased with decreasing gap size. The avoidance task
      became very difficult below a wire separation of 30 cm, which corresponds to the
      average wingspan of E. fuscus. Two of the bats were able to pass without
      collisions down to a gap size of 10 cm in some of the flights. The other two bats
      only managed to master gap sizes down to 20 and 30 cm, respectively. They also
      performed distinctly worse at all other gap sizes. With increasing difficulty of
      the task, the bats changed their flight and echolocation behaviour. Especially at
      gap sizes of 30 cm and below, flight paths increased in height and flight speed
      was reduced. In addition, the bats emitted approach signals that were arranged in
      groups. At all gap sizes, the largest numbers of pulses per group were observed
      in the last group before passing the obstacle. The more difficult the obstacle
      avoidance task, the more pulses there were in the groups and the shorter the
      within-group pulse intervals. In comparable situations, the better-performing
      bats always emitted groups with more pulses than the less well-performing
      individuals. We hypothesize that the accuracy of target localization increases
      with the number of pulses per group and that each group is processed as a
      package. 

PMID- 24902746
TI  - Fast and slow processes underlie the selection of both step frequency and walking
      speed.
AB  - People prefer gaits that minimize their energetic cost. Research focused on step
      frequency selection suggests that a fast predictive process and a slower
      optimization process underlie this energy optimization. Our purpose in this study
      was to test whether the mechanisms controlling step frequency selection are used
      more generally to select one of the most relevant characteristics of walking -
      preferred speed. To accomplish this, we contrasted the dynamic adjustments in
      speed following perturbations to step frequency against the dynamic adjustments
      in step frequency following perturbations to speed. Despite the use of different
      perturbations and contexts, we found that the responses were very similar. In
      both experiments, subjects responded to perturbations by first rapidly changing
      their speed or step frequency towards their preferred pattern, and then slowly
      adjusting their gait to converge onto their preferred pattern. We measured
      similar response times for both the fast processes (1.4+/-0.3 versus 2.7+/-0.6 s)
      and the slow processes (74.2+/-25.4 versus 79.7+/-20.2 s). We also found that the
      fast process, although quite variable in amplitude, dominated the adjustments in
      both speed and step frequency. These distinct but complementary experiments
      demonstrate that people appear to rely heavily on prediction to rapidly select
      the most relevant aspects of their preferred gait and then gradually fine-tune
      that selection, perhaps using direct optimization of energetic cost. 

PMID- 24902747
TI  - Enhanced memory persistence is blocked by a DNA methyltransferase inhibitor in
      the snail Lymnaea stagnalis.
AB  - Lymnaea stagnalis provides an excellent model system for studying memory because
      these snails have a well-described set of neurons, a single one of which controls
      expression of long-term memory of operantly conditioned respiratory behavior. We
      have shown that several different manipulations, including pre-training exposure
      to serotonin (5-HT) or methamphetamine, submersion of snails after training to
      prevent memory interference, and exposure to effluent from predatory crayfish
      (CE), enhance memory persistence. Changes in DNA methylation underlie formation
      of strong memories in mammals and 5-HT-enhanced long-term facilitation in
      Aplysia. Here we determined the impact of the DNA methyltransferase inhibitor, 5
      aza-2'-deoxycytidine (5-AZA; 87 MUmol l(-1)), on enhanced memory persistence by
      all four manipulations. We found that 5-HT (100 MUmol l(-1)) enhanced memory
      persistence, which was blocked by 5-AZA pretreatment. Snails pre-exposed to 3.3
      MUmol l(-1) Meth 4 h prior to training demonstrated memory 72 h later, which was
      not present in controls. This memory-enhancing effect was blocked by pre
      treatment with 87 MUmol l(-1) 5-AZA. Similarly, submersion to prevent
      interference learning as well as training in CE produced memory that was not
      present in controls, and these effects were blocked by pre-treatment with 87
      MUmol l(-1) 5-AZA. In contrast, 5-AZA injection did not alter expression of
      normal (non-enhanced) memory, suggesting that these four stimuli enhance memory
      persistence by increasing DNA methyltransferase activity, which, in turn,
      increases expression of memory-enhancing genes and/or inhibits memory suppressor
      genes. These studies lay important groundwork for delineating gene methylation
      changes that are common to persistent memory produced by different stimuli. 

PMID- 24902748
TI  - The oxidative cost of unstable social dominance.
AB  - High social rank is expected to incur fitness costs under unstable social
      conditions. A disruption of the oxidative balance may underlie such effects, but
      how markers of oxidative stress vary in relation to social rank and stability is
      unknown. We examined in mandrills whether the mating season characterized by
      social instability between males (but not between females) affected their
      oxidative balance differently according to their social rank. Outside the mating
      season, high-ranking males showed the lowest levels of oxidative damage, while
      during the mating season, they were the only males to experience increased
      oxidative damage. In contrast, the mating season increased oxidative stress in
      all females, irrespective of their social rank. These results support the
      hypothesis that the coupling between social rank and social stability is
      responsible for differential costs in terms of oxidative stress, which may
      explain inter-individual differences in susceptibility to socially induced health
      issues.

PMID- 24902749
TI  - Ultraviolet vision in lacertid lizards: evidence from retinal structure, eye
      transmittance, SWS1 visual pigment genes and behaviour.
AB  - Ultraviolet (UV) vision and UV colour patches have been reported in a wide range
      of taxa and are increasingly appreciated as an integral part of vertebrate visual
      perception and communication systems. Previous studies with Lacertidae, a lizard
      family with diverse and complex coloration, have revealed the existence of UV
      reflecting patches that may function as social signals. However, confirmation of
      the signalling role of UV coloration requires demonstrating that the lizards are
      capable of vision in the UV waveband. Here we use a multidisciplinary approach to
      characterize the visual sensitivity of a diverse sample of lacertid species.
      Spectral transmission measurements of the ocular media show that wavelengths down
      to 300 nm are transmitted in all the species sampled. Four retinal oil droplet
      types can be identified in the lacertid retina. Two types are pigmented and two
      are colourless. Fluorescence microscopy reveals that a type of colourless droplet
      is UV-transmitting and may thus be associated with UV-sensitive cones. DNA
      sequencing shows that lacertids have a functional SWS1 opsin, very similar at 13
      critical sites to that in the presumed ancestral vertebrate (which was UV
      sensitive) and other UV-sensitive lizards. Finally, males of Podarcis muralis are
      capable of discriminating between two views of the same stimulus that differ only
      in the presence/absence of UV radiance. Taken together, these results provide
      convergent evidence of UV vision in lacertids, very likely by means of an
      independent photopigment. Moreover, the presence of four oil droplet types
      suggests that lacertids have a four-cone colour vision system. 

PMID- 24902750
TI  - Cold-induced depolarization of insect muscle: differing roles of extracellular K+
      during acute and chronic chilling.
AB  - Insects enter chill coma, a reversible state of paralysis, at temperatures below
      their critical thermal minimum (CTmin), and the time required for an insect to
      recover after a cold exposure is termed chill coma recovery time (CCRT). The
      CTmin and CCRT are both important metrics of insect cold tolerance that are used
      interchangeably, although chill coma recovery is not necessarily permitted by a
      direct reversal of the mechanism causing chill coma onset. Nevertheless, onset
      and recovery of coma have been attributed to loss of neuromuscular function due
      to depolarization of muscle fibre membrane potential (Vm). Here we test the
      hypothesis that muscle depolarization at chill coma onset and repolarization
      during chill coma recovery are caused by changes in extracellular [K(+)] and/or
      other effects of low temperature. Using Locusta migratoria, we measured in vivo
      muscle resting potentials of the extensor tibialis during cooling, following
      prolonged exposure to -2 degrees C and during chill coma recovery, and related
      changes in Vm to transmembrane [K(+)] balance and temperature. Although Vm was
      rapidly depolarized by cooling, hemolymph [K(+)] did not rise until locusts had
      spent considerable time in the cold. Nonetheless, a rise in hemolymph [K(+)]
      during prolonged cold exposure further depressed muscle resting potential and
      slowed recovery from chill coma upon rewarming. Muscle resting potentials had a
      bimodal distribution, and with elevation of extracellular [K(+)] (but not
      temperature) muscle resting potentials become unimodal. Thus, a disruption of
      extracellular [K(+)] does depolarize muscle resting potential and slow CCRT
      following prolonged cold exposure. However, onset of chill coma at the CTmin
      relates to an as-yet-unknown effect of temperature on neuromuscular function. 

PMID- 24902751
TI  - Blood flow for bone remodelling correlates with locomotion in living and extinct
      birds.
AB  - Nutrient arteries enter limb bones through discrete foramina on the shafts. They
      are required for bone remodelling in response to mechanical loading and dynamic
      forces imposed by locomotion. The cross-sectional area of the nutrient foramen of
      the femur represents an index of blood flow rate to the shaft and thus provides
      insight into the animal's level of activity. Morphometric data on femoral length,
      mass and foramen size from 100 extant bird species and eight extinct moa species
      were analysed allometrically and phylogenetically. The nutrient foramen blood
      flow index (Qi) and femur mass (Mf) increase with body mass (Mb). At 1 kg body
      mass, cursorial species have approximately 2.1 times higher Qi and 1.9 times
      heavier Mf than volant species. The scaling of Qi on Mf is independent of the
      primary mode of locomotion, but the ratio Qi/Mf decreases significantly in larger
      birds, although absolute Qi increases. The overall avian equation for Qi on Mb is
      not significantly different from previous data from mammals, but when differences
      in blood pressure are accounted for, estimated blood flow to the femur is
      approximately 1.9 times higher in cursorial birds than in mammals, possibly in
      relation to bipedalism and quadrupedalism, respectively. Femoral bone blood flow
      in both endothermic groups is estimated to be 50-100 times higher than in
      ectothermic reptiles. 

PMID- 24902752
TI  - Strong negative effects of simulated heat waves in a tropical butterfly.
AB  - Climate change poses a significant challenge to all natural systems on Earth.
      Especially increases in extreme weather events such as heat waves have the
      potential to strongly affect biodiversity, though their effects are poorly
      understood because of a lack of empirical data. Therefore, we here explore the
      sensitivity of a tropical ectotherm, which are in general believed to have a low
      warming tolerance, to experimentally simulated climate change using ecologically
      realistic diurnal temperature cycles. Increasing the mean temperature permanently
      by 3 degrees C had mostly minor effects on developmental traits in the butterfly
      Bicyclus anynana. Simulated heat waves (strongly elevated temperatures for some
      time though retaining the same overall temperature mean), in contrast, caused
      strong negative effects by prolonging development time (by up to 10%) and
      reducing body mass (-21%), especially when combined with reduced relative
      humidity. Detrimental effects were carried over into the adult stage, diminishing
      subsequent performance. Most strikingly, higher temperatures suppressed adult
      immune function (haemocytes: -54%, lysozyme activity: -32%), which may
      potentially change the way species interact with antagonists. Heat waves thus
      reduced fitness parameters by 10-25% for development time and body mass and by up
      to 54% for immune parameters even in this plastic and widespread butterfly,
      exemplifying the potentially dramatic impact of extreme weather events on
      biodiversity. 

PMID- 24902754
TI  - Physical environments, policies and practices for physical activity and screen
      based sedentary behaviour among preschoolers within child care centres in
      Melbourne, Australia and Kingston, Canada.
AB  - BACKGROUND: Characteristics of preschool and child care centres have previously
      been shown to be associated with children's health behaviours such as physical
      activity and screen-based sedentary behaviour. This paper investigates
      differences in physical environments, policies and practices between child care
      centres in Melbourne, Australia and Kingston, Canada which may be associated with
      such behaviours. METHODS: Audits of child care centres were undertaken by trained
      research assistants for the Healthy Active Preschool and Primary Years
      (Melbourne, Australia; n = 136) study and the Healthy Living Habits in Pre-School
      Children (Kingston, Canada; n = 46) study. Twenty-one of the audit items (nine
      physical environment; 12 policies and practices) were assessed in both samples.
      Example items included outdoor play and shaded areas, availability of equipment,
      physical activity instruction for children and staff, opportunities to use
      electronic media and staff/child interaction during physical activity time.
      Analyses were completed using SAS version 9.2. RESULTS: Compared with Australian
      centres, a higher per cent of Canadian centres had a formal physical activity
      policy, reported children sat more frequently for 30 min or more and allowed
      children to watch television. A higher per cent of Australian centres provided an
      indoor area for physical activity, shade outdoors and physical activity education
      to staff. Children in Australian centres had access to more fixed play equipment
      and spent more time outdoors than in Canadian centres. CONCLUSIONS: These
      findings may help inform the development of best practice and policy guidelines
      to enhance opportunities for healthy levels of physical activity and screen-based
      sedentary behaviour within child care centres in both countries.

PMID- 24902753
TI  - Multiplexed modulation of behavioral choice.
AB  - Stimuli in the environment, as well as internal states, influence behavioral
      choice. Of course, animals are often exposed to multiple external and internal
      factors simultaneously, which makes the ultimate determinants of behavior quite
      complex. We observed the behavioral responses of European leeches, Hirudo
      verbana, as we varied one external factor (surrounding water depth) with either
      another external factor (location of tactile stimulation along the body) or an
      internal factor (body distention following feeding). Stimulus location proved to
      be the primary indicator of behavioral response. In general, anterior stimulation
      produced shortening behavior, midbody stimulation produced local bending, and
      posterior stimulation usually produced either swimming or crawling but sometimes
      a hybrid of the two. By producing a systematically measured map of behavioral
      responses to body stimulation, we found wide areas of overlap between behaviors.
      When we varied the surrounding water depth, this map changed significantly, and a
      new feature - rotation of the body along its long axis prior to swimming -
      appeared. We found additional interactions between water depth and time since
      last feeding. A large blood meal initially made the animals crawl more and swim
      less, an effect that was attenuated as water depth increased. The behavioral map
      returned to its pre-feeding form after approximately 3 weeks as the leeches
      digested their blood meal. In summary, we found multiplexed impacts on behavioral
      choice, with the map of responses to tactile stimulation modified by water depth,
      which itself modulated the impact that feeding had on the decision to swim or
      crawl. 

PMID- 24902755
TI  - Co-occurring malformations of cortical development and SCN1A gene mutations.
AB  - OBJECTIVE: To report on six patients with SCN1A mutations and malformations of
      cortical development (MCDs) and describe their clinical course, genetic findings,
      and electrographic, imaging, and neuropathologic features. METHODS: Through our
      database of epileptic encephalopathies, we identified 120 patients with SCN1A
      mutations, of which 4 had magnetic resonance imaging (MRI) evidence of MCDs. We
      collected two further similar observations through the European Task-force for
      Epilepsy Surgery in Children. RESULTS: The study group consisted of five males
      and one female (mean age 7.4 +/- 5.3 years). All patients exhibited
      electroclinical features consistent with the Dravet syndrome spectrum, cognitive
      impairment, and autistic features. Sequencing analysis of the SCN1A gene detected
      two missense, two truncating, and two splice-site mutations. Brain MRI revealed
      bilateral periventricular nodular heterotopia (PNH) in two patients and focal
      cortical dysplasia (FCD) in three, and disclosed no macroscopic abnormality in
      one. In the MRI-negative patient, neuropathologic study of the whole brain
      performed after sudden unexpected death in epilepsy (SUDEP), revealed multifocal
      micronodular dysplasia in the left temporal lobe. Two patients with FCD underwent
      epilepsy surgery. Neuropathology revealed FCD type IA and type IIA. Their seizure
      outcome was unfavorable. All four patients with FCD exhibited multiple seizure
      types, which always included complex partial seizures, the area of onset of which
      co-localized with the region of structural abnormality. SIGNIFICANCE: MCDs and
      SCN1A gene mutations can co-occur. Although epidemiology does not support a
      causative role for SCN1A mutations, loss or impaired protein function combined
      with the effect of susceptibility factors and genetic modifiers of the phenotypic
      expression of SCN1A mutations might play a role. MCDs, particularly FCD, can
      influence the electroclinical phenotype in patients with SCN1A-related epilepsy.
      In patients with MCDs and a history of polymorphic seizures precipitated by
      fever, SCN1A gene testing should be performed before discussing any epilepsy
      surgery option, due to the possible implications for outcome.

PMID- 24902756
TI  - Testosterone deficiency in patients with erectile dysfunction: when should a
      higher cardiovascular risk be considered?
AB  - INTRODUCTION: Low testosterone levels (low T) increase the cardiovascular (CV)
      risk of men with erectile dysfunction (ED). T levels associated with a higher CV
      risk are unknown. AIM: To determine the prevalence of CV risk factors associated
      with low T as defined by European Guidelines and their contribution to low T,
      overall and at different ages. METHODS: Multicenter, cross-sectional,
      observational study conducted in Spain among men with ED aged >= 18 years
      visiting Urology/Andrology offices for sexual dysfunction. Anthropometric,
      clinical, and laboratory data, including total T (TT) values, were collected for
      1,278 men. MAIN OUTCOME MEASURES: Risk factors were assessed in men with TT <= 8,
      8-12, and >= 12 nmol/L, and two-group comparisons were made. Bivariate and
      multivariate logistic regression analyses were performed to calculate odds ratios
      for low T after adjusting for possible confounding factors. RESULTS: Mean age
      (standard deviation) was 58.0 (9.2) years. Age and prevalence of CV risk factors
      was similar in men with TT <= 8 nmol/L or 8-12 nmol/L and significantly higher
      than in men with TT >12 nmol/L. Low T was therefore considered as TT <= 12
      nmol/L, with a prevalence of 33.3%. Obesity, hypertension, hyperlipidemia, and
      severe ED were the variables most strongly associated with low T: obesity in
      middle-aged men; hyperlipidemia, and hypertension in older men. Severe ED was a
      risk factor in both groups. Hypolipidemic therapy had the greater effect in young
      men. Multivariate analysis showed that severe ED and obesity were the strongest
      predictors of low T. CONCLUSION: T levels associated with increased CV risk could
      go as high as 12 nmol/L in men with ED, with distribution of risk factors showing
      differences according to age. Obesity and severe ED are the best predictors of
      low T-related CV risk.

PMID- 24902757
TI  - Clinical features and WNT10A mutations in seven unrelated cases of Schopf-Schulz
      Passarge syndrome.
AB  - BACKGROUND: Schopf-Schulz-Passarge syndrome (SSPS) is an autosomal recessive form
      of ectodermal dysplasia resulting from mutations in WNT10A. OBJECTIVES: To
      document the spectrum of clinical features and search for pathogenic mutations in
      seven unrelated cases of SSPS. METHODS: Clinical examination of patients and
      Sanger sequencing of genomic DNA spanning the coding exons and flanking spice
      sites of WNT10A. RESULTS: Most subjects had bilateral eyelid cysts and some
      degree of palmoplantar keratoderma, although nail, hair, and teeth abnormalities
      were variably present. Bi-allelic pathogenic mutations in WNT10A were found in
      all seven subjects. New mutations comprised p.Glu390*, p.Ser270Arg, and
      p.Cys362Arg; the recurrent mutations were p.Cys107* and p.Ala131Thr. CONCLUSIONS:
      This study reveals the range of ectodermal pathology in cases of SSPS that result
      from WNT10A mutations. Eyelid cysts provide a useful clinical clue to diagnosing
      SSPS which may be less rare than is currently appreciated.

PMID- 24902758
TI  - Family burden and family environment: comparison between patients with panic
      disorder and with clinical diseases.
AB  - AIMS: The objective of this study was to compare the family burden and
      environment of patients with panic disorder (PD) with those of a control group
      composed of relatives of patients with clinical diseases. METHODS: A cross
      sectional study was performed with 67 relatives of patients with PD, and 66
      family members of patients with clinical diseases. All patients were administered
      a set of instruments to assess family burden and environment. RESULTS:
      Multivariate analyses revealed significant between-group differences on
      measurements of objective and subjective burden, both of which can be influenced
      by kinship, since higher levels of family burden tend to be reported by the
      children of the affected individual. Levels of family burden also tend to be
      associated with the severity of PD symptoms. CONCLUSIONS: The assessment of
      family burden may be useful in developing family-focused therapeutic strategies
      and may contribute to the improvement of patient outcomes.

PMID- 24902759
TI  - Topical antibiotics may be useful for the prevention of surgical site infection
      under some circumstances.

PMID- 24902760
TI  - Comparison of bioimpedance and clinical methods for dry weight prediction in
      maintenance hemodialysis patients.
AB  - BACKGROUND: Bioelectrical impedance analysis (BIA) is a promising technique to
      evaluate dry weight. We compared the dry weight calculated by the three BIA
      equations Carlo Basile (CB) , Yanna Dou (YD) and the body composition
      spectroscopy (BCS) with clinical evaluation in maintenance hemodialysis (MHD)
      patients. METHODS: The dry weight of enrolled MHD patients (DWClin) was evaluated
      under strict clinical surveillance. The whole-body resistances at 50 kHz, intra-
      and extracellular resistances were measured to calculate the dry weight (DWCB,
      DWYD and DWBCS) using each of the three equations. RESULTS: Neither DWCB nor
      DWBCS were statistically different compared to DWClin (DWCB 63.2 +/- 17.2 vs.
      63.1 +/- 16.1 kg; DWBCS 62.8 +/- 16.8 vs. 63.1 +/- 16.1 kg, p > 0.05). DWYD was
      significantly lower than DWClin (DWYD 62.0 +/- 16.1 vs. 63.1 +/- 16.1 kg, p <
      0.05). The bias between DWCB and DWClin was the smallest among these three
      methods (DeltaDWCB -0.1 +/- 1.4 kg; DeltaDWYD 1.1 +/- 2.9 kg; DeltaDWBCS 0.3 +/-
      1.8 kg). CONCLUSION: The CB equations have better consistency with clinical dry
      weight in MHD patients.

PMID- 24902761
TI  - Radionuclide leakage monitoring during hyperthermic isolated limb perfusion for
      treatment of local melanoma metastasis in an extremity.
AB  - INTRODUCTION: The aim is to describe the importance of leakage monitoring in
      hyperthermic isolated limb perfusion (ILP). It is generally recommended that
      leakage should not exceed 10% because of risk of systemic toxicity. MATERIAL AND
      METHODS: Data retrieved by retrospective analysis of 131 perfusions performed in
      115 consecutive patients (77 women and 38 men; median age 66 years) with
      recurrent and/or clinically apparent, cutaneous or subcutaneous melanoma
      metastases in an extremity. Radionuclide monitoring was performed with
      continuous, precordial count rate determinations of an intravascular (99m) Tc
      labelled tracer infused into the isolated limb circulation. RESULTS: One hundred
      and sixteen of 131 procedures were completed. In 13%, a leakage of >=10% was
      detected; in 6% (n = 8), the cytotoxic drug was never infused because of constant
      leakage; in 7% (n = 9), leakage >=10% was measured during the perfusion resulting
      in two perfusions being terminated before 30 min, 5 perfusions were considered
      completed though with early termination (after 30 min, before 60 min), and 2
      fully completed. No patients had systemic toxicity requiring treatment, whereas
      considerable or serious local toxicity were observed in 14%. Three of the
      patients with leakage >=10% were successfully treated in a repeated procedure.
      CONCLUSION: Leakage monitoring using a threshold of 10% during ILP saves the
      patients from systemic toxicity, however, at the expense of early termination or
      cancellation of ILP treatment in a few patients and repeated ILP procedures in
      some.

PMID- 24902762
TI  - Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and
      asthma exacerbations.
AB  - BACKGROUND: We investigated the interaction between genetic variants in endotoxin
      signalling pathway and domestic endotoxin exposure in relation to asthma
      presence, and amongst children with asthma, we explored the association of these
      genetic variants and endotoxin exposure with hospital admissions due to asthma
      exacerbations. METHODS: In a case-control study, we analysed data from 824
      children (417 asthmatics, 407 controls; age 5-18 yr). Amongst asthmatics, we
      extracted data on hospitalization for asthma exacerbation from medical records.
      Endotoxin exposure was measured in dust samples collected from homes. We included
      26 single-nucleotide polymorphisms (SNPs) in the final analysis (5 CD14, 7LY96
      and 14 TLR4). RESULTS: Two variants remained significantly associated with
      hospital admissions with asthma exacerbations after correction for multiple
      testing: for CD14 SNP rs5744455, carriers of T allele had decreased risk of
      repeated hospital admissions compared with homozygotes for C allele [OR (95% CI),
      0.42 (0.25-0.88), p = 0.01, False Discovery Rate (FDR) p = 0.02]; for LY96 SNP
      rs17226566, C-allele carriers were at a lower risk of hospital admissions
      compared with T-allele homozygotes [0.59 (0.38-0.90), p = 0.01, FDR p = 0.04]. We
      observed two interactions between SNPs in CD14 and LY96 with environmental
      endotoxin exposure in relation to hospital admissions due to asthma exacerbation
      which remained significant after correction for multiple testing (CD14 SNPs
      rs2915863 and LY96 SNP rs17226566). CONCLUSION: Amongst children with asthma,
      genetic variants in CD14 and LY96 may increase the risk of hospital admissions
      with acute exacerbations. Polymorphisms in endotoxin pathway interact with
      domestic endotoxin exposure in further modification of the risk of
      hospitalization.

PMID- 24902764
TI  - Association of COPD exacerbation frequency with gene expression of pattern
      recognition receptors in inflammatory cells in induced sputum.
AB  - BACKGROUND: Bacteria and viruses are major causes of chronic obstructive
      pulmonary disease (COPD) exacerbations. Molecular components of these pathogens
      are recognized by pattern-recognition receptors (PRRs) expressed by various cells
      in the airway, which leads to initiation of inflammatory processes. Expression
      levels of PRRs in airway inflammatory cells are expected to affect susceptibility
      to COPD exacerbation. AIMS: This prospective observational study was conducted to
      detect any association between exacerbation and PRR expression. METHODS: Thirty
      one male COPD patients were recruited. At baseline, clinical history, lung
      function measurements, peripheral blood samples and induced sputum were obtained.
      Using sputum samples, we performed gene expression analysis of TLR2, TLR3, TLR4,
      NOD1, NOD2, RIG-I and MDA-5 by quantitative reverse transcription-polymerase
      chain reaction in addition to quantitative bacterial culture. COPD exacerbations
      were assessed based on Anthonisen's criteria using symptom diaries for the
      following 1-year period. RESULTS: During 1-year follow-up period, 13 patients
      experienced at least one exacerbation, but 18 patients did not. Those with
      exacerbations tended to be more severe COPD and showed larger neutrophil fraction
      in their induced sputum. Among PRRs, only TLR3 gene expression was increased in
      COPD patients with exacerbation compared with those without exacerbations.
      Multivariate logistic regression analysis including neutrophil fraction and TLR3
      gene expression as predictor variables demonstrated that only an increase of
      neutrophil fraction, but not TLR3 gene expression, was a significant predictor
      for COPD exacerbation. CONCLUSION: TLR3 expression in inflammatory cells might
      affect the susceptibility to COPD exacerbation.

PMID- 24902766
TI  - Protective effects of Fc-fused PD-L1 on two different animal models of colitis.
AB  - OBJECTIVE: Programmed death-ligand 1 (PD-L1) has been shown to negatively
      regulate immune responses via its interaction with PD-1 receptor. In this study,
      we investigated the effects of PD-L1-Fc treatment on intestinal inflammation
      using two murine models of inflammatory colitis induced by dextran sulfate sodium
      (DSS) and T-cell transfer. DESIGN: The anti-colitis effect of adenovirus
      expressing Fc-conjugated PD-L1 (Ad/PD-L1-Fc) and recombinant PD-L1-Fc protein was
      evaluated in DSS-treated wild-type and Rag-1 knockout (KO) mice. We examined
      differentiation of T-helper cells, frequency of innate immune cells, and cytokine
      production by dendritic cells (DCs) in the colon from DSS-treated mice after PD
      L1-Fc administration. In Rag-1 KO mice reconstituted with CD4 CD45RB(high) T
      cells, we assessed the treatment effect of PD-L1-Fc protein on the development of
      colitis. RESULTS: Administration of Ad/PD-L1-Fc significantly ameliorated DSS
      induced colitis, which was accompanied by diminished frequency of interleukin
      (IL)-17A-producing CD4 T cells and increased interferon-gamma-producing CD4 T
      cells in the colon of DSS-fed mice. The anti-colitic effect of PD-L1-Fc treatment
      was also observed in DSS-treated Rag-1 KO mice, indicating lymphoid cell
      independency. PD-L1-Fc modulated cytokine production by colonic DCs and the
      effect was dependent on PD-1 expression. Furthermore, PD-L1-Fc protein could
      significantly reduce the severity of colitis in CD4 CD45RB(high) T-cell
      transferred Rag-1 KO mice. CONCLUSIONS: Based on the protective effect of PD-L1
      Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1
      mediated inhibitory signals have a crucial role in limiting the development of
      colonic inflammation. This implicates that PD-L1-Fc may provide a novel
      therapeutic approach to treat inflammatory bowel disease.

PMID- 24902765
TI  - Osteopontin neutralisation abrogates the liver progenitor cell response and
      fibrogenesis in mice.
AB  - BACKGROUND: Chronic liver injury triggers a progenitor cell repair response, and
      liver fibrosis occurs when repair becomes deregulated. Previously, we reported
      that reactivation of the hedgehog pathway promotes fibrogenic liver repair.
      Osteopontin (OPN) is a hedgehog-target, and a cytokine that is highly upregulated
      in fibrotic tissues, and regulates stem-cell fate. Thus, we hypothesised that OPN
      may modulate liver progenitor cell response, and thereby, modulate fibrotic
      outcomes. We further evaluated the impact of OPN-neutralisation on murine liver
      fibrosis. METHODS: Liver progenitors (603B and bipotential mouse oval liver) were
      treated with OPN-neutralising aptamers in the presence or absence of transforming
      growth factor (TGF)-beta, to determine if (and how) OPN modulates liver
      progenitor function. Effects of OPN-neutralisation (using OPN-aptamers or OPN
      neutralising antibodies) on liver progenitor cell response and fibrogenesis were
      assessed in three models of liver fibrosis (carbon tetrachloride, methionine
      choline deficient diet, 3,5,-diethoxycarbonyl-1,4-dihydrocollidine diet) by
      quantitative real time (qRT) PCR, Sirius-Red staining, hydroxyproline assay, and
      semiquantitative double-immunohistochemistry. Finally, OPN expression and liver
      progenitor response were corroborated in liver tissues obtained from patients
      with chronic liver disease. RESULTS: OPN is overexpressed by liver progenitors in
      humans and mice. In cultured progenitors, OPN enhances viability and wound
      healing by modulating TGF-beta signalling. In vivo, OPN-neutralisation attenuates
      the liver progenitor cell response, reverses epithelial-mesenchymal-transition in
      Sox9+ cells, and abrogates liver fibrogenesis. CONCLUSIONS: OPN upregulation
      during liver injury is a conserved repair response, and influences liver
      progenitor cell function. OPN-neutralisation abrogates the liver progenitor cell
      response and fibrogenesis in mouse models of liver fibrosis.

PMID- 24902767
TI  - Overcoming barriers to the implementation of patient-reported outcomes in cancer
      clinical trials: the PROMOTION Registry.
AB  - Every cancer treatment, irrespective of its clinical effectiveness, has an impact
      on patients' quality of life (QoL). Even recently developed targeted therapies
      might have side effects and significantly impact patients' QoL. Thus,
      understanding the advantages and disadvantages of different treatments from the
      patient's standpoint has become a must in clinical research and is highly valued
      by major stakeholders. Thousands of cancer patients are enrolled into randomized
      controlled trials (RCTs) each year and many complete patient-reported outcome
      (PRO) instruments to obtain patient-centered information as part of the
      assessment of the overall effectiveness of the new therapy. Some of these RCTs
      have generated high quality PRO evidence forming the basis for approval (or
      support to approval) of drugs by the US Food and Drug Administration. However, a
      consistent strategy to determine the quality of patient centered evidence
      presented in RCTs has until recently been lacking. One of the fundamental
      questions when including PROs in clinical research revolves around methodological
      robustness and consistency of outcome reporting. Cancer patients, physicians and
      healthcare system stakeholders need to rely on solid information to make the best
      possible choice regarding treatment. Therefore generating high-quality findings
      from PRO assessment in cancer trials is of paramount importance. In an effort to
      improve quality of PRO assessment and reporting in the near future, the Patient
      Reported Outcome Measurements Over Time In ONcology (PROMOTION) Registry was
      developed. The scope of this Registry is to identify, track, analyse, and store
      information on all cancer RCTs that have included PROs, and assess the quality of
      their PRO assessments. 

PMID- 24902768
TI  - An overview of the treatment of severe narcissistic pathology.
AB  - This paper provides an overview of narcissistic personality disorders as they
      present clinically along a spectrum of severity ranging from the best functioning
      forms of pathological narcissism to the most threatening to the patient's
      psychosocial and physical survival. It proposes a general interpretive
      psychoanalytic stance with all these clinical syndromes that range from standard
      psychoanalysis to a specific psychoanalytical psychotherapy for the most
      repressive and life threatening conditions that may not respond to standard
      psychoanalysis proper. This general psychoanalytic approach is placed into the
      context of related developments in contemporary psychoanalytic understanding of
      pathological narcissism and its treatment. 

PMID- 24902770
TI  - Outcome disparities among ethnic subgroups of Waldenstrom's macroglobulinemia: a
      population-based study.
AB  - BACKGROUND: Ethnic disparities in cancers are associated with variability in
      clinical outcomes. We present a Surveillance Epidemiology and End RESULTS (SEER)
      based outcome analysis of multiethnic Waldenstrom's macroglobulinemia (WM)
      patients. METHODS: Adult WM patients diagnosed in 1992 or later (n = 3,175) were
      analyzed. Median overall survival (OS) was compared across different ethnicities
      stratified by year of diagnosis, registry identification, age at diagnosis, sex,
      and marital status. RESULTS: African-Americans (AA) had the youngest median age
      at diagnosis (63 years) and Whites had the oldest (73 years) (p < 0.001). Female
      gender, a younger age at diagnosis, and a recent year of diagnosis were
      associated with an improved OS. Hispanics had the worst (5.6 years) while Whites
      had the best (6.8 years) median OS. A significant interaction existed between
      median OS, gender, and race (p = 0.007). Among males, AA had the worst (4.3
      years) and Asians had the best (7.3 years) median OS. A significant interaction
      was also noted between median OS, age at diagnosis, and race (p = 0.033). The
      worst median OS was seen in Hispanics among patients aged >75 years, and in AA
      among those aged <65 years. CONCLUSIONS: These disparities among WM patients may
      be multifactorial but need to be explored systematically to better understand the
      disease biology and for optimal triaging of health care resources.

PMID- 24902769
TI  - Pt(IV) prodrugs designed to bind non-covalently to human serum albumin for drug
      delivery.
AB  - Albumin is the most abundant protein in human serum and drugs that are
      administered intravenously inevitably interact with it. We present here a series
      of platinum(IV) prodrugs designed specifically to enhance interaction with human
      serum albumin (HSA) for drug delivery. This goal is achieved by asymmetrically
      functionalizing the axial ligands of the prodrug so as to mimic the overall
      features of a fatty acid. Systematic variation of the length of the aliphatic
      tail tunes the cellular uptake and, consequently, the cytotoxicity of
      cis,cis,trans-[Pt(NH3)2Cl2(O2CCH2CH2COOH)(OCONHR)], 4, where R is a linear alkyl
      group. Investigation of an analogue bearing a fluorophore conjugated to the
      succinate ligand confirmed that these compounds are reduced by biological
      reductants with loss of the axial ligands. Intracellular release of cisplatin
      from 4 was further confirmed by observing the characteristic effects of cisplatin
      on the cell cycle and morphology following treatment with the prodrug. The most
      potent member of series 4, for which R is a hexadecyl chain, interacts with HSA
      in a 1:1 stoichiometry to form the platinum-protein complex 7. The interaction is
      non-covalent and extraction with octanol completely removes the prodrug from an
      aqueous solution of HSA. Construct 7 is robust and can be isolated following fast
      protein liquid chromatography. The nature of the tight interaction was
      investigated computationally, and these studies suggest that the prodrug is
      buried below the surface of the protein. Consequently, complexation to HSA is
      able to reduce the rate of reduction of the prodrug by ascorbate. The lead
      compound from series 4 also exhibited significant stability in whole human blood,
      attributed to its interaction with HSA. This favorable redox profile, in
      conjunction with the established nonimmunogenicity, biocompatibility, and
      enhanced tumor accumulation of HSA, produces a system that holds significant
      therapeutic potential. 

PMID- 24902771
TI  - Regional hippocampal volumes and development predict learning and memory.
AB  - The hippocampus is an anatomically and functionally heterogeneous structure, but
      longitudinal studies of its regional development are scarce and it is not known
      whether protracted maturation of the hippocampus in adolescence is related to
      memory development. First, we investigated hippocampal subfield development using
      170 longitudinally acquired brain magnetic resonance imaging scans from 85
      participants aged 8-21 years. Hippocampal subfield volumes were estimated by the
      use of automated segmentation of 7 subfields, including the cornu ammonis (CA)
      sectors and the dentate gyrus (DG), while longitudinal subfield volumetric change
      was quantified using a nonlinear registration procedure. Second, associations
      between subfield volumes and change and verbal learning/memory across multiple
      retention intervals (5 min, 30 min and 1 week) were tested. It was hypothesized
      that short and intermediate memory would be more closely related to CA2-3/CA4-DG
      and extended, remote memory to CA1. Change rates were significantly different
      across hippocampal subfields, but nearly all subfields showed significant volume
      decreases over time throughout adolescence. Several subfield volumes were larger
      in the right hemisphere and in males, while for change rates there were no
      hemisphere or sex differences. Partly in support of the hypotheses, greater
      volume of CA1 and CA2-3 was related to recall and retention after an extended
      delay, while longitudinal reduction of CA2-3 and CA4-DG was related to learning.
      This suggests continued regional development of the hippocampus across
      adolescence and that volume and volume change in specific subfields
      differentially predict verbal learning and memory over different retention
      intervals, but future high-resolution studies are called for.

PMID- 24902772
TI  - Circumstances and causes of falls by patients at a Spanish acute care hospital.
AB  - RATIONALE, AIMS AND OBJECTIVES: A major problem in hospitals is that of falls,
      which can seriously reduce patients' quality of life. Fall rates vary
      considerably depending on health care practices, the hospital environment and the
      measurement method used. The aim of this study was to determine the
      characteristics of hospitalized acute patients who suffer falls, by analysing the
      distribution and the profile of these patients. METHODS: This is an analytic
      cross-sectional study conducted at a Spanish hospital. All patients who suffered
      a fall during hospitalization in 2011 were studied by analysing the computerized
      register of falls. Downton index, circumstances and consequences of falls were
      analysed. Descriptive statistics, bivariate analysis and logistic regression
      analysis were performed. RESULTS: The frequency of falls was 0.64%. The rate of
      falls increased with age (mean age: 71.06 years). The highest percentage occurred
      among patients in the medical care area (63.7%). The probability of suffering a
      fall was 1.33 times higher among men than women. Differences in age, type of risk
      of fall and circumstances were found, depending on the type of hospitalization.
      Multivariate analysis revealed that patients in the medical care area suffered
      more falls with consequences: 7.01 [95% confidence interval (CI): 1.34-36.79], as
      did the patients classified as 'low risk': 2.40 (CI 95%: 1.02-5.65). CONCLUSIONS:
      Falls have diverse causes. Determining these circumstances can contribute to
      promoting a culture of prevention and to reducing the injuries provoked by falls.
      Notification procedures should be standardized in order to enable comparisons
      among different environments.

PMID- 24902774
TI  - Identification of a novel kisspeptin with high gonadotrophin stimulatory activity
      in the dog.
AB  - Kisspeptin (KISS1) and its receptor (KISS1r) are essential for normal
      reproductive function in many species, but the role of kiss1/kiss1r signalling in
      the dog has not yet been elucidated. The aims of this study were to identify the
      canine kiss1 and kiss1r genes and to determine gonadotrophin and oestradiol
      stimulatory activity of KP-10, the shortest biologically active form of KISS1.
      Canine kiss1 and kiss1r genes were localized by comparing the reference dog
      genome with relevant human cDNA sequences, using BLASTn software. The amino acid
      sequence of canine KP-10 (YNWN V FGLR Y ) differs at two positions from human KP
      10 (YNWN S FGLR F ). A single bolus of canine KP-10 was administered
      intravenously to anoestrous Beagle bitches in dosages of 0, 0.1, 0.2, 0.3, 0.5,
      1, 5, 10, and 30 MUg/kg. Blood samples were collected before and after canine KP
      10 administration for the measurement of plasma luteinizing hormone (LH, all
      doses), follicle-stimulating hormone (FSH) and oestradiol (1-30 MUg/kg). From 0.2
      MUg/kg onwards, canine KP-10 resulted in a rapid and robust rise in plasma LH
      concentration (max. at 10 min). KP-10 also resulted in a rapid and robust rise in
      plasma FSH concentration (max. at 10-20 min). Plasma oestradiol concentration
      increased significantly after dosages of 1, 5, and 10 MUg/kg and reached a
      maximum at 60-90 min. In conclusion, canine KP-10 is a potent kisspeptin which
      elicits robust gonadotrophin and oestradiol responses in anoestrous bitches,
      suggesting that canine kiss1/kiss1r are cogent targets for modulating
      reproduction in dogs.

PMID- 24902773
TI  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents lipopolysaccharide
      (LPS)-induced, sepsis-related severe acute lung injury in mice.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an energy metabolism-related
      enzyme in the glycolytic pathway. Recently, it has been reported that GAPDH has
      other physiological functions, such as apoptosis, DNA repair and autophagy. Some
      in vitro studies have indicated immunological aspects of GAPDH function, although
      there is no definite study discussing the advantage of GAPDH as a therapeutic
      target. Here, we show that GAPDH has an anti-inflammatory function by using a
      lipopolysaccharide (LPS)-induced, sepsis-related severe acute lung injury (ALI)
      mouse model, which is referred to as acute respiratory distress syndrome (ARDS)
      in humans. GAPDH pre-injected mice were protected from septic death, and their
      serum levels of proinflammatory cytokines were significantly suppressed. In lung
      tissue, LPS-induced acute injury and neutrophil accumulation were strongly
      inhibited by GAPDH pre-injection. Pulmonary, proinflammatory cytokine gene
      expression and serum chemokine expression in GAPDH pre-injected mice were also
      reduced. These data suggest the therapeutic potential of GAPDH for sepsis-related
      ALI/ARDS. 

PMID- 24902775
TI  - Effectiveness of fluorescence-based methods to detect in situ demineralization
      and remineralization on smooth surfaces.
AB  - This study aimed to evaluate the effectiveness of fluorescence-based methods
      (DIAGNOdent, LF; DIAGNOdent pen, LFpen, and VistaProof fluorescence camera, FC)
      in detecting demineralization and remineralization on smooth surfaces in situ.
      Ten volunteers wore acrylic palatal appliances, each containing 6 enamel blocks
      that were demineralized for 14 days by exposure to a 20% sucrose solution and 3
      of them were remineralized for 7 days with fluoride dentifrice. Sixty enamel
      blocks were evaluated at baseline, after demineralization and 30 blocks after
      remineralization by two examiners using LF, LFpen and FC. They were submitted to
      surface microhardness (SMH) and cross-sectional microhardness analysis. The
      integrated loss of surface hardness (DeltaKHN) was calculated. The intraclass
      correlation coefficient for interexaminer reproducibility ranged from 0.21 (FC)
      to 0.86 (LFpen). SMH, LF and LFpen values presented significant differences among
      the three phases. However, FC fluorescence values showed no significant
      differences between the demineralization and remineralization phases.
      Fluorescence values for baseline, demineralized and remineralized enamel were,
      respectively, 5.4 +/- 1.0, 9.2 +/- 2.2 and 7.0 +/- 1.5 for LF; 10.5 +/- 2.0, 15.0
      +/- 3.2 and 12.5 +/- 2.9 for LFpen, and 1.0 +/- 0.0, 1.0 +/- 0.1 and 1.0 +/- 0.1
      for FC. SMH and DeltaKHN showed significant differences between demineralization
      and remineralization phases. There was a negative and significant correlation
      between SMH and LF and LFpen in the remineralization phase. In conclusion, LF and
      LFpen devices were effective in detecting demineralization and remineralization
      on smooth surfaces provoked in situ.

PMID- 24902776
TI  - From the editor.

PMID- 24902777
TI  - Structural architecture of the social network of a non-human primate (Macaca
      sylvanus): a study of its topology in La Foret des Singes, Rocamadour.
AB  - For a decade, technological or natural networks have appeared to have a common
      mathematical architecture. This type of architecture has a node connectivity
      which follows a power law distribution. This architecture confers to these
      networks a resistance property to the loss of nodes. Such properties are
      advantageous for evolutional networks through time. Thus, this architecture can
      be expected in animal social networks. Another characteristic commonly met
      concerns the structuration of the network into communities by the mechanism of
      assortative mixing by vertex degree (i.e. by the number of ties individuals
      have). Such a structure is a reflection of evolutional mechanisms: the
      preferential attachment and the triadic closure processes. Using recent
      analytical techniques on an affiliative social network in a non-human primate
      species (Macaca sylvanus), we analysed the mathematical architecture and its
      properties. We demonstrate that in spite of the use of a recent protocol supposed
      to permit this type of analysis, the type of distribution cannot be clearly
      determined, encouraging us to carefully interpret the results obtained until
      then. Nevertheless, we observed interesting properties of the network at an
      ecological and evolutional level with network resilience that allows a cohesive
      society to be maintained even when faced with a catastrophe (high predation,
      epidemic).

PMID- 24902778
TI  - Detection of anthelmintic resistance on two Irish beef research farms.

PMID- 24902779
TI  - Treatment of peroneal paralysis with transposition of vastus lateralis muscle in
      calves.
AB  - This study aimed to clinically evaluate the results achieved by using tendon
      transposition to treat postinjection peroneal paralysis in calves. The study
      material consisted of 23 calves in all of which the clinical history indicated
      the problem had occurred within 1-3 days of intramuscular injection. Each patient
      was administered medical treatment for three weeks. After that, a decision was
      made to perform tendon transposition in all the subjects because their prognosis
      was estimated to be poor. The owners of five of the calves did not agree to the
      operation, and so, medical treatment was continued. Following intrathecal
      anaesthesia, the vastus lateralis muscle was dissected at the insertion, and the
      musculus (m) extensor (ext) digitalis (dig) longus and m fibularis tertius were
      dissected at the origin in 18 calves. The tendon ends were joined by using the
      locking loop suture technique in the 18 calves. Follow-up after two to three
      months revealed hind limb use in all surgically treated calves, while the
      medically treated calves had to be slaughtered because of lameness and decubitus.
      The results of the present study suggest that the peroneal paralysis of calves
      can be successfully treated by a tendon transposition technique. 

PMID- 24902780
TI  - Modular mechatronic system for stationary bicycles interfaced with virtual
      environment for rehabilitation.
AB  - BACKGROUND: Cycling has been used in the rehabilitation of individuals with both
      chronic and post-surgical conditions. Among the challenges with implementing
      bicycling for rehabilitation is the recruitment of both extremities, in
      particular when one is weaker or less coordinated. Feedback embedded in virtual
      reality (VR) augmented cycling may serve to address the requirement for
      efficacious cycling; specifically recruitment of both extremities and exercising
      at a high intensity. METHODS: In this paper a mechatronic rehabilitation
      bicycling system with an interactive virtual environment, called Virtual Reality
      Augmented Cycling Kit (VRACK), is presented. Novel hardware components embedded
      with sensors were implemented on a stationary exercise bicycle to monitor
      physiological and biomechanical parameters of participants while immersing them
      in an augmented reality simulation providing the user with visual, auditory and
      haptic feedback. This modular and adaptable system attaches to commercially
      available stationary bicycle systems and interfaces with a personal computer for
      simulation and data acquisition processes. The complete bicycle system includes:
      a) handle bars based on hydraulic pressure sensors; b) pedals that monitor pedal
      kinematics with an inertial measurement unit (IMU) and forces on the pedals while
      providing vibratory feedback; c) off the shelf electronics to monitor heart rate
      and d) customized software for rehabilitation. Bench testing for the handle and
      pedal systems is presented for calibration of the sensors detecting force and
      angle. RESULTS: The modular mechatronic kit for exercise bicycles was tested in
      bench testing and human tests. Bench tests performed on the sensorized handle
      bars and the instrumented pedals validated the measurement accuracy of these
      components. Rider tests with the VRACK system focused on the pedal system and
      successfully monitored kinetic and kinematic parameters of the rider's lower
      extremities. CONCLUSIONS: The VRACK system, a virtual reality mechatronic bicycle
      rehabilitation modular system was designed to convert most bicycles in virtual
      reality (VR) cycles. Preliminary testing of the augmented reality bicycle system
      was successful in demonstrating that a modular mechatronic kit can monitor and
      record kinetic and kinematic parameters of several riders.

PMID- 24902781
TI  - Sweets for the foe - effects of nonstructural carbohydrates on the susceptibility
      of Quercus robur against Phytophthora quercina.
AB  - The root-rot pathogen Phytophthora quercina is a key determinant of oak decline
      in Europe. The susceptibility of pedunculate oak (Quercus robur) to this pathogen
      has been hypothesized to depend on the carbon availability in roots as an
      essential resource for defense. Microcuttings of Q. robur undergo an alternating
      rhythm of root and shoot growth. Inoculation of mycorrhizal (Piloderma croceum)
      and nonmycorrhizal oak roots with P. quercina was performed during both growth
      phases, that is, root flush (RF) and shoot flush (SF). Photosynthetic and
      morphological responses as well as concentrations of nonstructural carbohydrates
      (NSC) were analyzed. Infection success was quantified by the presence of pathogen
      DNA in roots. Concentrations of NSC in roots depended on the alternating
      root/shoot growth rhythm, being high and low during RF and SF, respectively.
      Infection success was high during RF and low during SF, resulting in a
      significantly positive correlation between pathogen DNA and NSC concentration in
      roots, contrary to the hypothesis. The alternating growth of roots and shoots
      plays a crucial role for the susceptibility of lateral roots to the pathogen. NSC
      availability in oak roots has to be considered as a benchmark for susceptibility
      rather than resistance against P. quercina. 

PMID- 24902782
TI  - Chiral transition-metal complexes as Bronsted-acid catalysts for the asymmetric
      Friedel-Crafts hydroxyalkylation of indoles.
AB  - The Friedel-Crafts reaction between 3,3,3-trifluoropyruvates and indoles is
      efficiently catalysed by the iridium complex [(eta(5)-C5Me5)Ir{(R)
      Prophos}(H2O)][SbF6]2 (1) with up to 84% ee. Experimental data and theoretical
      calculations support a mechanism involving the Bronsted-acid activation of the
      pyruvate carbonyl by the protons of the coordinated water molecule in 1. Water is
      not dissociated during the process and, therefore, the catalytic reaction occurs
      with no direct interaction between the substrates and the metal. 

PMID- 24902783
TI  - Nickel-doped cobalt ferrite nanoparticles: efficient catalysts for the reduction
      of nitroaromatic compounds and photo-oxidative degradation of toxic dyes.
AB  - This study deals with the exploration of NixCo1-xFe2O4 (x = 0.0, 0.2, 0.4, 0.6,
      0.8, 1.0) ferrite nanoparticles as catalysts for reduction of 4-nitrophenol and
      photo-oxidative degradation of Rhodamine B. The ferrite samples with uniform size
      distribution were synthesized using the reverse micelle technique. The structural
      investigation was performed using powder X-ray diffraction, high-resolution
      transmission electron microscopy, energy dispersive X-ray and scanning tunneling
      microscopy. The spherical particles with ordered cubic spinel structure were
      found to have the crystallite size of 4-6 nm. Diffused UV-visible reflectance
      spectroscopy was employed to investigate the optical properties of the
      synthesized ferrite nanoparticles. The surface area calculated using BET method
      was found to be highest for Co0.4Ni0.6Fe2O4 (154.02 m(2) g(-1)). Co0.4Ni0.6Fe2O4
      showed the best catalytic activity for reduction of 4-nitrophenol to 4
      aminophenol in the presence of NaBH4 as reducing agent, whereas CoFe2O4 was found
      to be catalytically inactive. The reduction reaction followed pseudo-first order
      kinetics. The effect of varying the concentration of catalyst and NaBH4 on the
      reaction rates was also scrutinized. The photo-oxidative degradation of Rhodamine
      B, enhanced oxidation efficacy was observed with the introduction of Ni(2+) in to
      the cobalt ferrite lattice due to octahedral site preference of Ni(2+). Almost
      99% degradation was achieved in 20 min using NiFe2O4 nanoparticles as catalyst.

PMID- 24902784
TI  - Nanoscopic optical rulers beyond the FRET distance limit: fundamentals and
      applications.
AB  - In the last few decades, Forster resonance energy transfer (FRET) based
      spectroscopy rulers have served as a key tool for the understanding of chemical
      and biochemical processes, even at the single molecule level. Since the FRET
      process originates from dipole-dipole interactions, the length scale of a FRET
      ruler is limited to a maximum of 10 nm. Recently, scientists have reported a
      nanomaterial based long-range optical ruler, where one can overcome the FRET
      optical ruler distance dependence limit, and which can be very useful for
      monitoring biological processes that occur across a greater distance than the 10
      nm scale. Advancement of nanoscopic long range optical rulers in the last ten
      years indicate that, in addition to their long-range capability, their
      brightness, long lifetime, lack of blinking, and chemical stability make
      nanoparticle based rulers a good choice for long range optical probes. The
      current review discusses the basic concepts and unique light-focusing properties
      of plasmonic nanoparticles which are useful in the development of long range one
      dimensional to three dimensional optical rulers. In addition, to provide the
      readers with an overview of the exciting opportunities within this field, this
      review discusses the applications of long range rulers for monitoring biological
      and chemical processes. At the end, we conclude by speculating on the role of
      long range optical rulers in future scientific research and discuss possible
      problems, outlooks and future needs in the use of optical rulers for
      technological applications. 

PMID- 24902785
TI  - Candidate genes for aggression and antisocial behavior: a meta-analysis of
      association studies of the 5HTTLPR and MAOA-uVNTR.
AB  - Variation in central serotonin levels due to genetic mutations or experimental
      modifications has been associated with the manifestation of aggression in humans
      and animals. Many studies have examined whether common variants in serotonergic
      genes are implicated in aggressive or antisocial behaviors (ASB) in human
      samples. The two most commonly studied polymorphisms have been the serotonin
      transporter linked polymorphic region of the serotonin transporter gene (5HTTLPR)
      and the 30 base pair variable number of tandem repeats of the monoamine oxidase A
      gene (MAOA-uVNTR). Despite the aforementioned theoretical justification for these
      polymorphisms, findings across studies have been mixed and are thus difficult to
      interpret. A meta-analysis of associations of the 5HTTLPR and MAOA-uVNTR with ASB
      was conducted to determine: (1) the overall magnitude of effects for each
      polymorphism, (2) the extent of heterogeneity in effect sizes across studies and
      the likelihood of publication bias, and (3) whether sample-level or study-level
      characteristics could explain observed heterogeneity across studies. Both the
      5HTTLPR and the MAOA-uVNTR were significantly associated with ASB across studies.
      There was also significant and substantial heterogeneity in the effect sizes for
      both markers, but this heterogeneity was not explained by any sample-level or
      study-level characteristics examined. We did not find any evidence for
      publication bias across studies for the MAOA-uVNTR, but there was evidence for an
      oversampling of statistically significant effect sizes for the 5HTTLPR. These
      findings provide support for the modest role of common serotonergic variants in
      ASB. Implications regarding the role of serotonin in antisocial behavior and the
      conceptualization of antisocial and aggressive phenotypes are discussed. 

PMID- 24902786
TI  - Testosterone ameliorates streptozotocin-induced memory impairment in male rats.
AB  - AIM: To study the effects of testosterone on streptozotocin (STZ)-induced memory
      impairment in male rats. METHODS: Adult male Wistar rats were
      intracerebroventricularly (icv) infused with STZ (750 MUg) on d 1 and d 3, and a
      passive avoidance task was assessed 2 weeks after the first injection of STZ.
      Castration surgery was performed in another group of rats, and the passive
      avoidance task was assessed 4 weeks after the operation. Testosterone (1 mg.kg(
      1).d(-1), sc), the androgen receptor antagonist flutamide (10 mg.kg(-1).d(-1),
      ip), the estrogen receptor antagonist tamoxifen (1 mg.kg(-1).d(-1), ip) or the
      aromatase inhibitor letrozole (4 mg.kg(-1).d(-1), ip) were administered for 6 d
      after the first injection of STZ. RESULTS: STZ administration and castration
      markedly decreased both STL1 (the short memory) and STL2 (the long memory) in
      passive avoidance tests. Testosterone replacement almost restored the STL1 and
      STL2 in castrated rats, and significantly prolonged the STL1 and STL2 in STZ
      treated rats. Administration of flutamide, letrozole or tamoxifen significantly
      impaired the memory in intact rats, and significantly attenuated the testosterone
      replacement in improving STZ- and castration-induced memory impairment.
      CONCLUSION: Testosterone administration ameliorates STZ- and castration-induced
      memory impairment in male Wistar rats.

PMID- 24902787
TI  - Co-administration of paroxetine and pravastatin causes deregulation of glucose
      homeostasis in diabetic rats via enhanced paroxetine exposure.
AB  - AIM: Clinical evidence shows that co-administration of pravastatin and paroxetine
      deregulates glucose homeostasis in diabetic patients. The aim of this study was
      to verify this phenomenon in diabetic rats and to elucidate the underlying
      mechanisms. METHODS: Diabetes mellitus was induced in male SD rats by a high-fat
      diet combined with a low-dose streptozotocin injection. The rats were orally
      administered paroxetine (10 mg/kg) and pravastatin (10 mg/d) or both the drugs
      daily for 28 d. The pharmacokinetics of paroxetine and pravastatin were examined
      on d 1 and d 28. Biochemical parameters including serum insulin, glucose and
      lipids were monitored during the treatments. An insulin-secreting cell line (INS
      1) was used for measuring insulin secretion. RESULTS: In diabetic rats, co
      administration of paroxetine and pravastatin markedly increased the
      concentrations of both the drugs compared with administration of each drug alone.
      Furthermore, co-administration severely impaired glucose homeostasis in diabetic
      rats, as demonstrated by significantly increased serum glucose level, decreased
      serum and pancreatic insulin levels, and decreased pancreatic Insulin-2 mRNA and
      tryptophan hydroxylase-1 (Tph-1) mRNA levels. Treatment of INS-1 cells with
      paroxetine (5 and 10 MUmol/L) significantly inhibited insulin secretion,
      decreased the intracellular insulin, 5-HT, Insulin-2 mRNA and Tph-1 mRNA levels.
      Treatment of the cells with pravastatin (10 MUmol/L) significantly stimulated
      insulin secretion, which was weakened by co-treatment with paroxetine.
      CONCLUSION: Paroxetine inhibits insulin secretion at least via decreasing
      intracellular 5-HT and insulin biosynthesis. The deregulation of glucose
      homeostasis by co-administration of paroxetine and pravastatin in diabetic rats
      can be attributed to enhanced paroxetine exposure.

PMID- 24902788
TI  - Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+ acute
      myeloid leukemia cells in vitro.
AB  - AIM: Skewed cytoplasmic accumulation of NPM mutant protein (NPM1c+) is close
      related to leukemia pathogenesis. The aim of this study was to investigate
      whether oridonin, a diterpenoid isolated from the Chinese traditional medicine
      Rabdosia rubescens, was able to interfere with NPM1c+ protein trafficking and
      induce apoptosis in NPM1c+ acute myeloid leukemia cells in vitro. METHODS: OCI
      AML3 cell line harboring a NPM1 gene mutation was examined. Cell growth was
      detected by MTT assay. Cell apoptosis was evaluated using flow cytometry and
      Hoechst 33258 staining. The expression and subcellular localization of relevant
      proteins were detected by Western blot and immunofluorescent staining. The mRNA
      expression was detected by RT-PCR. RESULTS: Oridonin (2-12 MUmol/L) dose
      dependently inhibited the viability of OCI-AML3 cells (the IC50 value was 3.27+/
      0.23 MUmol/L at 24 h). Moreover, oridonin induced OCI-AML3 cell apoptosis
      accompanied by activation of caspase-3 and nuclear translocation of NPM1c+
      protein. Oridonin did not change the expression of Crm1 (the export receptor for
      nuclear export signal-containing proteins), but induced nuclear translocation of
      Crm1. Oridonin markedly increased the expression of nucleoporin98 (Nup98), which
      had an important role in Crm1-mediated nuclear protein export, and induced
      nuclear accumulation of Nup98. Furthermore, oridonin markedly increased the
      expression of p14arf and p53. CONCLUSION: In NPM1c+ leukemia cells, oridonin
      induces NPM1c+ protein translocation into the nucleus possibly via nuclear
      accumulation of Crm1; the compound markedly increases p53 and p14arf expression,
      which may contribute to cell apoptosis.

PMID- 24902789
TI  - Quercetin sensitizes human glioblastoma cells to temozolomide in vitro via
      inhibition of Hsp27.
AB  - AIM: Quercetin is an effective Hsp27 inhibitor and has been reported to
      facilitate tumor cell apoptosis. The aim of this study was to investigate whether
      quercetin could sensitize human glioblastoma cells to temozolomide (TMZ) in
      vitro. METHODS: Both U251 and U87 human glioblastoma cells were treated with
      quercetin and/or TMZ for 48 h. Cell viability was detected using the MTT assay.
      Cell apoptosis was analyzed with caspase-3 activity kits and flow cytometry.
      Hsp27 expression and phosphorylation were examined using Western blot analysis.
      RNA interference using Hsp27 siRNA oligos was performed to knock down the gene
      expression of Hsp27. RESULTS: TMZ (200 or 400 MUmol/L) alone effectively
      inhibited the viability of U251 and U87 cells. When combined with quercetin (30
      MUmol/L), TMZ (100 MUmol/L) significantly inhibited the cell viability, and the
      inhibition of TMZ (200 and 400 MUmol/L) was enhanced. TMZ or quercetin anole did
      not affect caspase-3 activity and cell apoptosis, while TMZ combined with
      quercetin significantly increased caspase-3 activity and induced cell apoptosis.
      TMZ anole significantly increased Hsp27 phosphorylation in U251 and U87 cells,
      while quercetin or Hsp27 siRNA oligos combined with TMZ attenuated TMZ-induced
      Hsp27 phosphorylation and significantly inhibited Hsp27 expression. CONCLUSION:
      Combined treatment with TMZ and quercetin efficiently suppressed human
      glioblastoma cell survival in vitro.

PMID- 24902790
TI  - Evaluation of doxorubicin-loaded pH-sensitive polymeric micelle release from
      tumor blood vessels and anticancer efficacy using a dorsal skin-fold window
      chamber model.
AB  - AIM: To evaluation the doxorubicin (DOX)-loaded pH-sensitive polymeric micelle
      release from tumor blood vessels into tumor interstitium using an animal vessel
      visibility model, the so-called dorsal skin-fold window chamber model. METHODS:
      DOX-loaded pH-sensitive polyHis-b-PEG micelles and DOX-loaded pH-insensitive PLLA
      b-PEG micelles were prepared. The uptake of the micelles by MDA-MB-231 breast
      cancer cells in vitro and in vivo was examined using flow cytometry. The
      pharmacokinetic parameters of the micelles were determined in SD rats after
      intravenous injection of a DOX dose (6 mg/kg). The release of the micelles from
      tumor vasculature and the antitumor efficacy were evaluated in MDA-MB-231 breast
      cancer xenografted in nude mice using a dorsal skin-fold window chamber. RESULTS:
      The effective elimination half-life t1/2 of the pH-sensitive, pH-insensitive
      polymeric micelles and DOX-PBS in rats were 11.3 h, 9.4 h, and 2.1 h,
      respectively. Intravital microscopy in MDA-MB-231 breast cancer xenografted in
      nude mice showed that the pH-sensitive polymeric micelles rapidly extravasated
      from the tumor blood vessels, and DOX carried by the pH-sensitive micelles was
      preferentially released at the tumor site as compared to the pH-insensitive
      polymeric micelles. Furthermore, the pH-sensitive polymeric micelles exhibited
      significant greater efficacy in inhibition of tumor growth in the nude mice.
      CONCLUSION: When DOX is loaded into pH-sensitive polymeric micelles, the acidity
      in tumor interstitium causes the destabilization of the micelles and triggers
      drug release, resulting in high local concentrations within the tumor, thus more
      effectively inhibiting the tumor growth in vivo.

PMID- 24902792
TI  - In vivo tricalcium phosphate, bone morphogenetic protein and autologous bone
      marrow biomechanical enhancement in vertebral fractures in a porcine model.
AB  - PURPOSE: Minimally invasive techniques that introduce cement and bone substitutes
      inside the fractured vertebral body are a new treatment line with clinically
      proven efficacy. However, mechanical behaviours between different fillers
      throughout fracture evolution is yet to be clarified, as many substances are
      available for introduction into the vertebral body fracture. METHODS: We
      comparatively studied biomechanical properties of tricalcium phosphate,
      tricalcium phosphate with bone morphogenetic protein (rhBMP-7) and autologous
      bone marrow aspirate with rhBMP-7 in vivo to determine what substance is optimal
      for repairing vertebral lesions in a porcine model. This biomechanical study was
      carried out with an Instron-type testing machine. Data registered were necessary
      strength to reach vertebral fracture [Newtons (N)], shortening (millimeters) of
      the vertebra, energy absorption until vertebral fracture (Joules) and vertebral
      unit stiffness. RESULTS: For statistical study, we used the SPSS 16 package at a
      significance level of alpha = 0.05. In the presentation of the results, mean,
      standard deviation of mean, median and interquartile range (IQR) were analysed.
      Mean and standard deviation (SD) of strength in newtons (N) for the vertebral
      fracture are 756 N (SD = 253) in group 1, 1,500 N (SD = 1598) in group 2 and
      1,230 N (SD = 1,598) in group 3. Stiffness after fracture was 229 N (SD = 123) in
      group 1, 277 N (SD = 135) in group 2 and 404 N (SD = 325) in group 3.
      CONCLUSIONS: The association of tricalcium phosphate and BMP-7 generates major
      vertebral resistance to external energy, the cause of such fractures. In such
      fractures, minor shortening occurs as soon as the vertebral body is fractured.
      Autologous bone marrow and BMP-7 provides increased biomechanical behavior, and
      the vertebral body is thus significantly strengthened.

PMID- 24902791
TI  - Lapatinib-incorporated lipoprotein-like nanoparticles: preparation and a proposed
      breast cancer-targeting mechanism.
AB  - AIM: Lapatinib is a dual inhibitor of EGFR and human epidermal growth factor
      receptor 2 (HER2), and used to treat advanced breast cancer. To overcome its poor
      water solubility, we constructed lapatinib-incorporated lipoprotein-like
      nanoparticles (LTNPs), and evaluated the particle characteristics and possible
      anti-breast cancer mechanisms. METHODS: LTNPs (lapatinib bound to albumin as a
      core, and egg yolk lecithin forming a lipid corona) were prepared. The particle
      characteristics were investigated using transmission electron microscopy (TEM)
      and atomic force microscopy (AFM). The uptake and subcellular localization of
      LTNPs, as well as the effects of LTNPs on cell cycle were examined in BT-474
      human breast cancer cells in vitro. Mice bearing BT-474 subcutaneous xenograft
      were intravenously injected with coumarin-6 loaded LTNPs (30 mg/kg) to study the
      targeting mechanisms in vivo. RESULTS: The LTNPs particles were generally
      spherical but flexible under TEM and AFM, and approximately 62.1 nm in size with
      a zeta potential of 22.80 mV. In BT-474 cells, uptake of LTNPs was mediated by
      endosomes through energy-dependent endocytosis involving clathrin-dependent
      pinocytosis and macropinocytosis, and they could effectively escape from
      endosomes to the cytoplasm. Treatment of BT-474 cells with LTNPs (20 MUg/mL)
      induced a significant cell arrest at G0/G1 phase compared with the same
      concentration of lapatinib suspension. In mice bearing BT-474 xenograft,
      intravenously injected LTNPs was found to target and accumulate in tumors, and
      colocalized with HER2 and SPRAC (secreted protein, acidic and rich in cysteine).
      CONCLUSION: LTNPs can be taken up into breast cancer cells through specific
      pathways in vitro, and targeted to breast cancer xenograft in vivo via enhanced
      permeability and retention effect and SPARC.

PMID- 24902794
TI  - Electrodiagnostics in myelopathy.

PMID- 24902793
TI  - Bone marrow enriched graft, modified by self-assembly peptide, repairs critically
      sized femur defects in goats.
AB  - PURPOSE: This study focuses on nanoscale self-assembly peptides (SAP) modified
      demineralized bone matrix (DBM) which provided a more effective osteogenesis and
      regeneration for critically-sized femur defects in goats using the selective cell
      retention (SCR) strategy. METHODS: RADA16-I peptide was used to modify DBM and
      formed a composite scaffold (SAP/DBM). The morphological change and dynamic
      expression of osteogenic genes of mesenchymal stem cells (MSCs) derived from
      marrow in SAP/DBM was observed. The cells and factors in bone marrow were
      enriched into SAP/DBM by technology of selective cells retension (SCR). The
      construct was transplanted into 20-mm femur defects in goats and their
      osteogenesis was evaluated. RESULTS: The SAP/DBM scaffold formed a three
      dimensional interweaving nanofiber in pores of DBM. MSCs exhibited better
      morphology in SAP/DBM than that in only DBM, and the levels of expression of ALP
      ,OCN and Runx2 gene in SAP/DBM samples was significantly higher than that of DBM
      at 14 days in vitro (P < 0.05). Compared with marrow-enriched DBM, the volume of
      newly formed bone from marrow-enriched SAP/DBM is higher in goats (P < 0.05).
      CONCLUSION: Our study may not only have a significant impact on the construction
      method of tissue engineering but also provide a viable, simple and effective
      method for clinical bone construction.

PMID- 24902795
TI  - Understanding infection susceptibility in patients with acute-on-chronic liver
      failure.

PMID- 24902797
TI  - A woman with swelling of the posterior pharyngeal wall.

PMID- 24902796
TI  - The synergism of biochemical components controlling lipid oxidation in lamb
      muscle.
AB  - Lipid oxidation of M. longissimus lumborum in fresh or vacuum packaged (aged)
      lamb meat stored at 3  degrees C for 0 or 4 weeks, respectively and displayed
      under refrigerated conditions for a further 4 days was assessed by measuring the
      concentration of malondialdehyde (MDA) in meat using the thiobarbituric acid
      reactive substances procedure. The effects of vitamin E, heme iron and
      polyunsaturated fatty acids (n-6 and n-3) on lipid oxidation were examined.
      Results showed a strong positive relationship between heme iron, n-6 and n-3
      fatty acids and lipid oxidation when vitamin E was below 2.95 mg/kg muscle. When
      lipid oxidation was related to vitamin E concentration and the other three
      variables, respectively, any increase in heme iron or n-6 or n-3 fatty acids
      concentration did not influence lipid oxidation. Management of diet to elevate
      muscle vitamin E concentration above 3.45 mg/kg muscle is beneficial to maintain
      the level of lipid oxidation below 2.4 mg MDA/kg muscle in meat stored for up to
      4 weeks. This demonstrates that vitamin E concentration in muscle has a greater
      influence on controlling lipid oxidation in muscle tissues than do heme iron or
      polyunsaturated fatty acids. 

PMID- 24902798
TI  - IL-22 enhances CCL20 production in IL-1beta-stimulated human gingival
      fibroblasts.
AB  - CC chemokine ligand 20 (CCL20) is involved in the recruitment of Th17 cells and
      thus in the exacerbation of periodontal disease, but the effect of simultaneous
      interleukin (IL)-22 and IL-1beta stimulation on CCL20 production in human
      gingival fibroblasts (HGFs) is uncertain. In this study, we investigated the
      mechanisms of IL-1beta- and/or IL-22-induced CCL20 production in HGFs. A single
      stimulation of IL-22 could not induce CCL20 production. On the other hand, IL-22
      could increase CCL20 production from IL-1beta-stimulated HGFs in a dose-dependent
      manner. C-Jun N terminal kinase (JNK) and inhibitor of nuclear factor kappaB
      (IkappaB)-alpha phosphorylation were increased in IL-1beta- and IL-22-stimulated
      HGFs. An inhibitor of nuclear factor (NF)-kappaB decreased IL-1beta- and IL-22
      induced CCL20 production, though an inhibitor of JNK did not modulate CCL20
      production. These data suggest that IL-1beta in cooperation with IL-22 could
      increase Th17 cell accumulation in periodontally diseased tissues to enhance
      CCL20 production in HGFs. 

PMID- 24902799
TI  - Identification of ERF genes in peanuts and functional analysis of AhERF008 and
      AhERF019 in abiotic stress response.
AB  - Ethylene-responsive factor (ERF) play an important role in regulating gene
      expression in plant development and response to stresses. In peanuts (Arachis
      hypogaea L.), which produce flowers aerially and pods underground, only a few ERF
      genes have been identified so far. This study identifies 63 ERF unigenes from
      247,313 peanut EST sequences available in the NCBI database. The phylogeny, gene
      structures, and putative conserved motifs in the peanut ERF proteins were
      analysed. Comparative analysis revealed the absence of two subgroups (A1 and A3)
      of the ERF family in peanuts; only 10 subgroups were identified in peanuts
      compared to 12 subgroups in Arabidopsis and soybeans. AP2/ERF domains were found
      to be conserved among peanuts, Arabidopsis, and soybeans. Outside the AP2/ERF
      domain, many soybean-specific conserved motifs were also detected in peanuts. The
      expression analysis of ERF family genes representing each clade revealed
      differential expression patterns in response to biotic and abiotic stresses.
      Overexpression of AhERF008 influenced the root gravity of Arabidopsis, whereas
      overexpression of AhERF019 enhanced tolerance to drought, heat, and salt stresses
      in Arabidopsis. The information generated in this study will be helpful to
      further investigate the function of ERFs in plant development and stress
      response. 

PMID- 24902800
TI  - Defining the role of trimetazidine in the treatment of cardiovascular disorders:
      some insights on its role in heart failure and peripheral artery disease.
AB  - Trimetazidine is a cytoprotective drug whose cardiovascular effectiveness,
      especially in patients with stable ischemic heart disease, has been the source of
      much controversy in recent years; some have gone so far as to treat the
      medication as a 'placebo drug' whose new side effects, such as Parkinsonian
      symptoms, outweigh its benefits. This article is an attempt to present the recent
      key studies, including meta-analyses, on the use of trimetazidine in chronic
      heart failure, also in patients with diabetes mellitus and arrhythmia, as well as
      in peripheral artery disease. This paper also includes the most recent European
      Society of Cardiology guidelines, including those of 2013, on the use of
      trimetazidine in cardiovascular disease. 

PMID- 24902801
TI  - Palatovaginal (pharyngeal) artery: clinical implication and surgical experience.
AB  - The palatovaginal or pharyngeal artery is a small branch of the internal
      maxillary artery supplying the nasopharynx. Bleeding from this artery is
      exceptional and only one case of traumatic epistaxis from this artery has been
      reported previously. We report a case of a 66-year-old male presenting with right
      recurrent posterior epistaxis. Endoscopic dissection of the pterygopalatine fossa
      and direct visualization of the palatosphenoidal canal permitted to identify the
      origin of bleeding, and coagulation of the pharyngeal artery solved the
      epistaxis. Although rare, intractable posterior epistaxis may arise from the
      pharyngeal artery. The anatomical knowledge of this artery and of the
      palatosphenoidal canal is of outmost importance in endoscopic transpterygoid and
      nasopharyngeal procedures, to identify the vidian canal, evaluate nasopharyngeal
      cancer spread in the pterygopalatine fossa, reduce bleeding during surgery of the
      nasopharynx, and harvest adequately the pedicle of the nasoseptal flap. 

PMID- 24902802
TI  - Polyhexanide-containing solution reduces ciliary beat frequency of human nasal
      epithelial cells in vitro.
AB  - In ENT, polyhexanide-containing solutions are used to treat nasal infections
      caused by multiresistant bacteria like methicillin-resistant Staphylococcus
      aureus. Many forms of commercial nasal solutions containing polyhexanide exist,
      such as gels or solutions for topical use. Data regarding the influence of
      polyhexanide on ciliary beat frequency (CBF) are lacking to date. We tested the
      CBF of nasal ciliated epithelial cells under the influence of a commercially
      available polyhexanide-containing solution (Lavasept((r)) Concentrate) in a
      therapeutic concentration (0.04, 0.02%). In addition, we tested the
      concentrations of 0.1 and 0.01%. Cells were visualized with a phase contrast
      microscope, and the CBF was measured with the SAVA system's region of interest
      method. Ringer's solution and macrogol served as negative controls. A therapeutic
      concentration of Lavasept significantly reduced CBF in a time- and concentration
      dependent manner. After 1 min, the CBF was reduced from 8.90 +/- 1.64 to 5.00 +/-
      3.72 Hz with a concentration of 0.04% (p value = 0.001). After 10 min, all cilia
      stopped beating. After 5 min, a 0.02% solution of Lavasept concentrate decreased
      CBF significantly from 8.64 +/- 1.71 to 3.30 +/- 3.27 Hz (p value < 0.001). In
      conclusion, CBF of human nasal epithelia is significantly reduced with the use of
      the polyhexanide-containing solution Lavasept in some therapeutic concentrations.
      Due to our findings in this study, Lavasept should be used on ciliated mucosa
      only with caution and in a concentration of 0.02%.

PMID- 24902803
TI  - Ovine ear model for fully endoscopic stapedectomy training.
AB  - Endoscopic surgery of the middle ear is progressively gaining the interest of
      otologists, as technological advances have overcome some of its main drawbacks.
      The long learning curve required to master this technique, urges the search for
      models to practice it. After the validation of sheep's ear as a proper training
      model for microscopic stapedectomy, our objective is to demonstrate its adequacy
      for practicing stapes surgery but performed through a fully endoscopic approach.
      Endoscopic stapedectomy was performed by two surgeons in 40 sheep ears (20
      specimens each). To analyze the effects of the learning curve on surgical
      success, complication rates and surgical time reduction, the sample was divided
      in two groups: group 1 being the first ten procedures of each surgeon, and group
      2 the second set of stapedectomies. The impact of the operated side and the
      resection of the chordal spine were also studied. No statistically significant
      differences were found considering the operated side. A statistically significant
      improvement in some of the surgical steps was demonstrated comparing both groups
      and also after the resection of the chordal spine. Mean surgical time declined
      from 38 to 31.5 min (p < 0.05). Using this model for endoscopic stapedectomy, a
      learning curve was objectively demonstrated, along with other subjective
      appreciations such as improvement in depth perception and one-hand instrument
      handling. We believe that sheep ear is an optimal model for endoscopic middle ear
      surgery, as it allows for the acquisition of the skills required to master this
      technique.

PMID- 24902804
TI  - Unfolding the role of PET FDG scan in the management of thyroid incidentaloma in
      cancer patients.
AB  - Thyroid incidentaloma detected on FDG-PET scan has been reported repeatedly in
      the last several years, though conflicting data are reported. Our aim is to
      identify the incidence and outcome of incidental FDG-PET detected thyroid lesions
      in patients undergoing FDG-PET scan for other primary malignancies and to suggest
      a management algorithm. This is a retrospective review of all patients who had a
      FDG-PET detected incidental thyroid lesion between January 2002 and December 2009
      at Peter MacCallum Cancer Center. Demographics, data relating to PET scan
      findings, FNA diagnoses, operative details, and histopathology were reviewed. Of
      the 1,034 subjects who underwent the FDG-PET study, 51 (4.9%) were identified as
      having thyroid incidentaloma, 31 females and 20 males with a mean age of 60
      years. Thyroid malignancy was noted in 39.5% (19/48 patients) who underwent FNAB.
      Sixteen underwent thyroidectomy. The histopathology revealed 12 patients with
      papillary carcinoma, 5 with follicular carcinoma and 2 with medullary carcinoma.
      The high rates are in concordance with analysis of the rates published in the
      literature. In patients with thyroid PET incidentaloma, the incidence of primary
      thyroid malignancy is very high as reported in our study and based on analysis of
      published data, necessitating further investigation. If assessment of these
      incidentalomas suggests malignancy, then appropriate surgical management may be
      warranted according to the patient's medical condition.

PMID- 24902805
TI  - [Management of dysphagia in internal intensive-care medicine].
AB  - Physicians specializing in dysphagia are needed in modern intensive care
      medicine. Long-term intubation is associated with aspiration and swallowing
      disorders. Early and standardised dysphagia management should be initiated during
      a patient's stay on intensive care unit. A clinically experienced,
      interdisciplinary team is required to provide optimal care for critically ill
      patients with dysphagia. Intensive care physicians should therefore know about
      basics in dysphagiology. 

PMID- 24902807
TI  - Lectin-like ox-LDL receptor-1 (LOX-1)-Toll-like receptor 4 (TLR4) interaction and
      autophagy in CATH.a differentiated cells exposed to angiotensin II.
AB  - Toll-like receptors (TLRs) play an essential role in innate immune response.
      Expression of TLRs has also been linked to autophagy. As the main receptor for
      oxidized low-density lipoprotein (ox-LDL) on the cell surface, lectin-like ox-LDL
      receptor-1 (LOX-1) is upregulated by proinflammatory cytokines and has been
      linked to the development of autophagy. However, the relationship between LOX-1,
      autophagy, and TLR4 in neurons has not been defined. Here, we show that
      Angiotensin II (Ang II) treatment of CATH.a differentiated neuronal cells
      resulted in the expression of TLR4 (and associated signals MyD88 and
      Toll/interleukin-1 receptor domain-containing adapter-inducing interferon
      (TRIF)), LOX-1 autophagy. LOX-1 knockdown (transfection with specific small
      interfering RNA (siRNA)) resulted in reduced expression of TLR4 (and associated
      signals MyD88 and TRIF) and P-P38 mitogen-activated protein kinase (MAPK) and
      autophagy. TLR4 knockdown with siRNA resulted in reduced LOX-1 expression and
      autophagy, indicating a positive feedback between LOX-1 and TLR4. Knockdown of
      TRIF as well as MyD88 or inhibition of P38 MAPK also inhibited the expression of
      LOX-1 and TLR4 and autophagy. Importantly, pretreatment with 3-methyladenine
      (autophagy inhibitor) enhanced while rapamycin (autophagy inducer) decreased the
      expression of LOX-1, TLR4, and P-P38 MAPK. These studies suggest the presence of
      a bidirectional link between LOX-1and TLR4 in cultured CATH.a differentiated
      cells exposed to Ang II with an important role for autophagy in this link.

PMID- 24902808
TI  - Analyses of the similarity and difference of global gene expression profiles in
      cortex regions of three neurodegenerative diseases: sporadic Creutzfeldt-Jakob
      disease (sCJD), fatal familial insomnia (FFI), and Alzheimer's disease (AD).
AB  - Neurodegenerative disease is a general designation for the disorders that are
      progressive loss of structure or function and final death of neurons, including
      Alzheimer's, Parkinson's, Huntington's, prion diseases, etc. In this study, we
      comparatively analyzed 21 individual microarray data sets of the cortex tissues
      from 11 sporadic Creutzfeldt-Jakob disease (sCJD), 3 fatal familial insomnia
      (FFI), 3 Alzheimer's disease (AD), and 4 normal controls. After normalization, a
      collection of 730 differently expressed sets (DESets) were obtained by comparison
      of the data of three diseases with their original controls. Principal component
      analysis (PCA) showed a background-related distribution within the groups of FFI,
      AD, and normal control, but two apparently different subgroups within the group
      of sCJD were observed. Review of the clinical materials of 11 sCJD patients
      identified the difference in brain PrP(Sc) deposits between two subgroups.
      Hierarchical cluster analysis illustrated the relatively independent clusters of
      normal controls, FFIs, six sCJD cases (subgroup 1) with more PrP(Sc) deposits,
      respectively, while an overlapped cluster of five cases of sCJD2 (subgroup 2)
      with less PrP(Sc) deposits and AD patients. Despite of the presence of special
      gene expressions, many common features were found among those neurodegenerative
      diseases. The most commonly changed biological processes (BPs) were signal
      transduction, synaptic transmission, and neuropeptide signaling pathway. The most
      commonly changed pathways were MAPK signaling pathway, Parkinson's disease, and
      oxidative phosphorylation. Our data here provide the similarity and difference in
      global gene expressions among the patients with sCJD, FFI, and AD, which may help
      to understand the common mechanism of neurodegenerative diseases. 

PMID- 24902809
TI  - Protective effects of Radix Pseudostellariae extract against retinal laser
      injury.
AB  - BACKGROUND: This study aimed to analyze the protective effects of a saponin
      extract from Radix Pseudostellariae (RP) on retinal laser injury based on a
      retinal photocoagulation model. METHODS: Fifty-eight rabbits were randomly
      divided into three groups: Group A (saponin extract orally), Group B
      (physiological saline), and Group C (control). The animals were sacrificed 1 day,
      7 days, 14 days, and 30 days after photocoagulation and lesions were evaluated
      with fundus photography, light microscopy, and electron microscopy. Superoxide
      dismutase (SOD) and malondialdehyde (MDA) levels were measured, and expression
      levels of c-fos and Bax genes were also determined. RESULTS: The lesion sizes in
      Group A were smaller than in Group B. The levels of SOD in Group B were
      significantly lower than in groups A and C (P<0.001) at all time points. The MDA
      levels were significantly lower than in groups B and C (P<0.001) at the 1 month
      point, while the apoptosis rate of Group A was significantly lower than that of
      Group B at all time points. The expression levels of the c-fos gene in Group B
      were significantly higher than that in groups A and C, and expression levels of
      the Bax gene in Group A were significantly lower than that in groups B and C.
      CONCLUSION: The saponin extract of RP can inhibit oxidative stress, downregulate
      the levels of c-fos and Bax gene expression, and inhibit apoptosis in the retina
      after photocoagulation.

PMID- 24902811
TI  - Toward scar-free surgery: an analysis of the increasing complexity from
      laparoscopic surgery to NOTES.
AB  - BACKGROUND: NOTES is an emerging technique for performing surgical procedures,
      such as cholecystectomy. Debate about its real benefit over the traditional
      laparoscopic technique is on-going. There have been several clinical studies
      comparing NOTES to conventional laparoscopic surgery. However, no work has been
      done to compare these techniques from a Human Factors perspective. This study
      presents a systematic analysis describing and comparing different existing NOTES
      methods to laparoscopic cholecystectomy. METHODS: Videos of
      endoscopic/laparoscopic views from fifteen live cholecystectomies were analyzed
      to conduct a detailed task analysis of the NOTES technique. A hierarchical task
      analysis of laparoscopic cholecystectomy and several hybrid transvaginal NOTES
      cholecystectomies was performed and validated by expert surgeons. To identify
      similarities and differences between these techniques, their hierarchical
      decomposition trees were compared. Finally, a timeline analysis was conducted to
      compare the steps and substeps. RESULTS: At least three variations of the NOTES
      technique were used for cholecystectomy. Differences between the observed
      techniques at the substep level of hierarchy and on the instruments being used
      were found. The timeline analysis showed an increase in time to perform some
      surgical steps and substeps in NOTES compared to laparoscopic cholecystectomy.
      CONCLUSION: As pure NOTES is extremely difficult given the current state of
      development in instrumentation design, most surgeons utilize different hybrid
      methods-combination of endoscopic and laparoscopic instruments/optics. Results of
      our hierarchical task analysis yielded an identification of three different
      hybrid methods to perform cholecystectomy with significant variability among
      them. The varying degrees to which laparoscopic instruments are utilized to
      assist in NOTES methods appear to introduce different technical issues and
      additional tasks leading to an increase in the surgical time. The NOTES continuum
      of invasiveness is proposed here as a classification scheme for these methods,
      which was used to construct a clear roadmap for training and technology
      development.

PMID- 24902810
TI  - A rapid single-tube protocol for HAV detection by nested real-time PCR.
AB  - Infections by food-borne viruses such as hepatitis A virus (HAV) and norovirus
      are significant public health concerns worldwide. Since food-borne viruses are
      rarely confirmed through direct isolation from contaminated samples, highly
      sensitive molecular techniques remain the methods of choice for the detection of
      viral genetic material. Our group has previously developed a specific nested real
      time PCR (NRT-PCR) assay for HAV detection that improved overall sensitivity.
      Furthermore in this study, we have developed a single-tube NRT-PCR approach for
      HAV detection in food samples that reduces the likelihood of cross contamination
      between tubes during sample manipulation. HAV RNA was isolated from HAV-spiked
      food samples and HAV-infected cell cultures. All reactions following HAV RNA
      isolation, including conventional reverse transcriptase PCR, nested-PCR, and RT
      PCR were performed in a single tube. Our results demonstrated that all the
      samples tested positive by RT-PCR and nested-PCR were also positive by a single
      tube NRT-PCR. The detection limits observed for HAV-infected cell cultures and
      HAV-spiked green onions were 0.1 and 1 PFU, respectively. This novel method
      retained the specificity and robustness of the original NRT-PCR method, while
      greatly reducing sample manipulation, turnaround time, and the risk of carry-over
      contamination. Single-tube NRT-PCR thus represents a promising new tool that can
      potentially facilitate the detection of HAV in foods thereby improving food
      safety and public health.

PMID- 24902812
TI  - Multidimensional analyses of the learning curve of robotic low anterior resection
      for rectal cancer: 3-phase learning process comparison.
AB  - BACKGROUND: Robotic surgery has advantages to perform rectal cancer by its
      ergonomic designs and advanced technologies. However, it was uncertain whether
      these core robotic technologies could shorten the learning curve. The aim of this
      study is to investigate the learning curve of robotic rectal cancer surgery and
      to compare the learning curve phases with respect to perioperative
      clinicopathologic outcomes. METHODS: From April 2006 to August 2011, a total of
      130 consecutive patients who were diagnosed with rectal cancer underwent a
      robotic low anterior resection (LAR) using the hybrid technique by a single
      surgeon at Severance Hospital. The moving average method and the cumulative sum
      (CUSUM) were used to analyze the learning curve. The risk-adjusted CUSUM (RA
      CUSUM) analysis was used to evaluate the points, which showed completion of
      surgical procedures in terms of R1 resection, conversion, postoperative
      complications, harvested lymph nodes less than 12, and local recurrence.
      Perioperative clinical outcomes and pathologic results were compared among the
      learning curve phases. RESULTS: According to the CUSUM, the learning curve was
      divided into three phases: phase 1 [the initial learning period (1st-44th case),
      n = 44], phase 2 [the competent period (45th-78th case), n = 34], and phase 3
      [the challenging period (79th-130th case), n = 52]. RA-CUSUM showed the minimum
      value at the 75th case, which suggested technical competence to satisfy feasible
      perioperative outcomes. The total operation time tended to decrease after phase 1
      and so did the surgeon console time and docking time. Postoperative complications
      and pathologic outcomes were not significantly different among the learning
      phases. CONCLUSIONS: The learning curve of robotic LAR consisted of three phases.
      The primary technical competence was achieved at phase 1 of the 44th case
      according to the CUSUM. The technical completion to assure feasible perioperative
      outcomes was achieved at phase 2 at the 75th case by the RA-CUSUM method.

PMID- 24902813
TI  - Long-term results of hepatic hydatid disease managed using palanivelu hydatid
      system: Indian experience in tertiary center.
AB  - BACKGROUND: Incidence of hepatic hydatid disease is increasing due to
      globalization. Surgery is the gold standard treatment. Laparoscopy has gained
      enough evidence regarding its safety and efficacy. Complete evacuation of hydatid
      contents without spillage remains a challenge. We aimed to determine long-term
      results of hepatic hydatid disease managed laparoscopically using palanivelu
      hydatid system (PHS) at our institution. METHODS: One hundred and five patients
      underwent laparoscopic surgical management using the PHS at our institute from
      May 1997 to May 2013. Clinical presentations, surgical strategy, postoperative
      morbidity, and long-term recurrence rate were evaluated. RESULTS: Of the 105
      patients, 76 were male and 29 female with a mean age of 32 years (range 14-71
      years). The most common presentation was abdominal pain in 61 patients (58%).
      Sixteen patients had multiple cysts of which nine had involvement of both lobes.
      Seventy-seven (73.3%) cysts were uncomplicated. Nineteen (18.09%) had a cyst
      biliary communication, two were ruptured cysts, and seven were recurrent cysts.
      All patients underwent successful laparoscopic management where conservative
      surgery was performed in 94 patients and radical surgery in 11 patients. Post
      operative morbidity was seen in 18 (17.14 %) patients, which included deep cavity
      infection in two cases, post-operative bile leak in 13 cases, and duodenal injury
      in one case without any mortality. Mean long-term follow-up was 36 months (range
      6 months-5 years) with recurrence in two cases. CONCLUSION: Our long-term results
      with PHS showed good outcomes in the laparoscopic management of hepatic hydatid
      disease with conservative surgery as the preferred approach reserving radical
      surgery only in selected cases.

PMID- 24902814
TI  - A prospective randomized controlled trial to compare single-port endo
      laparoscopic surgery versus conventional TEP inguinal hernia repair.
AB  - INTRODUCTION: The success of laparoscopic surgery is due to the less surgical
      trauma, including less operative pain, complications and better cosmetics.
      Objective of our study was to compare in two blind randomized groups of patients,
      the surgical outcome of total extra-peritoneal (TEP) inguinal hernia repair using
      either single-port or conventional surgical technique. We will report our interim
      results in the first group of 50 patients. MATERIALS AND METHODS: Our study is a
      prospective, randomized, controlled clinical trial conducted from August 2011 to
      June 2013. Fifty patients aged between 21 and 80 years undergoing surgery for
      unilateral inguinal hernia were randomised into two groups: conventional
      laparoscopic TEP inguinal hernia repair versus single-port TEP repair. Clinical
      data on patient demographics, surgical technique and findings, postoperative
      complications and pain scores were collected. Primary endpoint is the
      postoperative pain while secondary endpoints are recurrence, chronic pain,
      postoperative hospital stay and complications. RESULTS: Out of the 50 patients,
      26 underwent single-port hernia TEP repair and 24 had conventional 3-port TEP
      hernia repair after randomization. Mean operative time was 51.7 (+/-13.4) min in
      the multiport group and 59.3 (+/-14.9) min in the single-port group, respectively
      (P = 0.064). Mean hospital stay was 19.7 (+/-4.8) h in the conventional group and
      22.1 (+/-4.5) h in the single-port group (P = 0.079). No statistically
      significant differences were observed between the two groups for postoperative
      complications, and no recurrence reported at 11 months follow-up. There was no
      significant difference in the pain scores (visual analog scale) between the two
      groups at regular intervals post surgery. DISCUSSION: The outcomes after
      laparoscopic TEP inguinal hernia repair with a single-port device are comparable
      to the standard three-port technique.

PMID- 24902815
TI  - Threefold increased bile duct injury rate is associated with less surgeon
      experience in an insurance claims database: more rigorous training in biliary
      surgery may be needed.
AB  - INTRODUCTION: Bile duct injury (BDI) remains the dreaded complication of
      laparoscopic cholecystectomy (LC) over the last two decades. Although the
      Fundamentals of Laparoscopic Surgery (FLS) certification is now required for new
      applicants by the American Board of Surgery, the impact of FLS on procedure
      specific outcomes is unknown. Moreover, the FLS content centers on fundamental
      education and not procedure-specific complication reduction such as BDI,
      magnifying the importance of understanding the educational impact of FLS on
      specific case types. This study reviewed the impact of FLS certification and
      other factors on the incidence of bile duct injury in a large insurance claims
      database. METHODS: In total, 53,632 LCs were reviewed from July 2009 to December
      2010 from a large private payer claims database. Surgeon National Provider
      Identifier (NPI), FLS certification status, International Classification of
      Diseases, Ninth Revision (ICD-9) and Current Procedural Terminology (CPT) were
      available for each event. Each record was analyzed for evidence of any bile duct
      injury based on associated CPT or ICD-9 data in the claim record. Characteristics
      of the FLS+ and FLS- surgeon groups were analyzed by a separate reviewer blinded
      to clinical outcome on a large scale. RESULTS: A total of 53,632 LCs were
      reviewed; 1748 LC were performed by 441 FLS+ surgeons; and 58,870 LCs by 10,851
      FLS- surgeons. (Some procedures involved more than one surgeon). Eighty-two BDIs
      were identified: 8 in the FLS+ and 74 in the FLS- group. The FLS+ group had a
      higher rate of BDI than the FLS- group (0.47 vs. 0.14 %, p = 0.0013); however,
      the FLS+ group was also younger (mean age 38.2 FLS+ vs. 50.4 years) and had
      significantly fewer years in practice (FLS+ = 6.1 vs. FLS- = 20.7, p = 0.0012).
      No other complications showed differences between the groups. CONCLUSION: NPI can
      be used as a linking intermediary between skills certification and outcomes on
      claims databases. FLS certification was not associated with a reduction in bile
      duct injury in this analysis, but FLS+ surgeons were also younger and less
      experienced overall. Since FLS lacks content specific to BDI, large-scale
      validated training and assessment programs targeted at BDI prevention are needed
      to impact the rate of this complication during cholecystectomy.

PMID- 24902816
TI  - The effect of smoking on bariatric surgical outcomes.
AB  - BACKGROUND: Bariatric surgery is an effective long-term treatment for morbid
      obesity. Although smoking is known to increase postoperative complications, the
      independent effect of smoking on bariatric surgical outcomes is unclear. The
      purpose of this study was to investigate the effect of smoking on bariatric
      surgical outcomes using the National Surgical Quality Improvement Program
      (NSQIP). STUDY DESIGN: Bariatric patients from 2005 to 2010 were identified in
      NSQIP for all types of bariatric procedures except adjustable gastric banding.
      Pre-treatment variables' univariate associations with smoking were examined with
      chi-square and t tests. Association of smoking with outcomes, corrected for
      relevant covariates, was tested with logistic regression within laparoscopic and
      open treatment groups. RESULTS: A total of 41,445 patients underwent bariatric
      surgery (35,696 laparoscopic; 5,749 open). After controlling for covariates,
      smoking significantly increased the risk of organ space infection, prolonged
      intubation, reintubation, pneumonia, sepsis, shock, and longer length of stay in
      all patients undergoing bariatric surgery. In the open bariatric surgery
      subgroup, smoking was associated with a significantly higher incidence of organ
      space infection, prolonged intubation, pneumonia, and length of stay. In the
      laparoscopic surgery subgroup, smokers had a significantly increased incidence of
      prolonged intubation, reintubation, sepsis, shock, and length of stay. Smoking
      did not significantly increase the risk of mortality for patients undergoing
      bariatric surgery. CONCLUSIONS: These data suggest that smoking is a modifiable
      preoperative risk factor that significantly increases the incidence of
      postoperative morbidity but not mortality in both laparoscopic and open bariatric
      surgery. Smoking cessation may minimize the risk of adverse outcomes. Future
      investigation is needed to identify the optimal length of preoperative smoking
      cessation.

PMID- 24902817
TI  - Colonoscopy performance correlates with scores on the FESTM manual skills test.
AB  - INTRODUCTION: Achieving proficiency in flexible endoscopy is a major priority for
      general surgery training programs. The Fundamentals of Endoscopic Surgery (FESTM)
      is a high-stakes examination of the knowledge and skills required to perform
      flexible endoscopy. The objective of this study was to establish additional
      evidence for the validity of the FESTM hands-on test as a measure of flexible
      endoscopy skills by correlating clinical colonoscopy performance with FESTM
      score. METHODS: Participants included FESTM-naive general surgery residents,
      gastroenterology fellows at all levels of training and attending physicians who
      regularly perform colonoscopy. Each participant completed a live colonoscopy and
      the FESTM hands-on test within 2 weeks. Performance on live colonoscopy was
      measured using the Global Assessment of Gastrointestinal Endoscopic Skills
      Colonoscopy (GAGES-C, maximum score 20), and performance on the FESTM hands-on
      test was assessed by the simulator's computerized scoring system. The clinical
      assessor was blinded to simulator performance. Scores were compared using
      Pearson's correlation coefficient. RESULTS: A total of 24 participants were
      enrolled (mean age 30; 54 % male) with a broad range of endoscopy experience; 17
      % reported no experience, 54 % had <25 previous colonoscopies; and 21 % had >100.
      The FESTM and GAGES scores reflected the broad range of endoscopy experience of
      the study group (FESTM score range 32-105; GAGES score range 5-20). Pearson's
      correlation coefficient between GAGES-C scores and FESTM hands-on test scores was
      0.78 (0.54-0.90, p < 0.0001). All eight participants with GAGES-C score >15/20
      achieved a passing score on the FESTM hands-on test. CONCLUSION: There is a
      strong correlation between clinical colonoscopy performance and scores achieved
      on the FESTM hands-on test. These data support the validity of FESTM as a measure
      of colonoscopy skills.

PMID- 24902818
TI  - Single-stage versus 2-stage sleeve gastrectomy as a conversion after failed
      adjustable gastric banding: 30-day outcomes.
AB  - BACKGROUND: Sleeve gastrectomy (SG) is being performed as a conversion after
      adjustable gastric banding (AGB), often in a single stage. However, some argue
      that it should be performed in 2 stages to improve safety. Few studies compare
      complications between 1-stage and 2-stage procedures. Our aim is to compare the
      30-day complication rates among these two groups. METHODS: We retrospectively
      reviewed patients converted from AGB to SG between 8/2008 and 10/2013 and
      compared patients undergoing 1-stage and 2-stage techniques. Primary outcome was
      overall 30-day adverse event rate (postoperative complication, readmission, or
      reoperation). Secondary outcomes included operating room (OR) time, length of
      stay (LOS), leak, infection, and bleeding rates, as well as mortality. RESULTS: A
      total of 83 patients underwent SG after band removal; three were excluded due to
      short follow-up, leaving 60 1-stage and 20 2-stage. Mean time from band removal
      to SG for 2-stage was 438 days. Demographics, intraoperative technique (bougie
      size, staple reinforcement, oversewing staple line, and leak test), and mean
      follow-up were not statistically different. Mean OR time (132.1 min 1-stage vs.
      127.8 min 2-stage, p = 0.702) and LOS (3.1 vs. 2.4 days, p = 0.676) were similar.
      Overall 30-day adverse event rate was 12 % for 1-stage versus 15 % for 2-stage
      procedures (p = 0.705). Differences in 30-day readmission (8 vs. 5 %) and
      reoperation (5 vs. 0 %) were not statistically significant (p = 0.999 and 0.569,
      respectively). Leak (3 vs. 0 %, p = 0.999), abscess (2 vs. 5 %, p = 0.440), and
      bleeding rates (2 vs. 0 %, p = 0.999) were not different. There were no deaths.
      CONCLUSIONS: SG performed as a conversion after AGB is safe and feasible. Our
      findings indicate no statistical difference in 30-day outcomes when performed in
      1 or 2 stages. Future studies with larger sample sizes are necessary to further
      investigate these differences.

PMID- 24902820
TI  - Opinions of forensic schizophrenia patients on the use of restraints:
      controversial legislative issues.
AB  - The use of restraints is a controversial issue even though legal regulations may
      seem straightforward. Our aims were to evaluate the forensic patients' opinions
      on certain aspects of restraining and to compare these opinions with the current
      legal norms. Inpatients with schizophrenia or schizoaffective disorder at the
      Department of Forensic Psychiatry in Popovaca, Croatia, were asked the following
      questions about the use of mechanical restraints: (a) Should the patients' family
      be informed about the use of restraints? (b) Should the physician ask the patient
      whether to inform the family about the use of restraints? (c) Can the use of
      restraints be a kind of punishment for intentionally aggressive behavior toward
      people in their environment? and (d) Should restraints be used if the patient
      requests to be restrained? The patients were assessed according to the
      Temperament and character inventory and Positive and Negative Symptom Scale.
      Fifty-four forensic patients with a history of serious offences were included in
      the study. Their average age was 44.7 (+/- 8.39) years and the mean duration of
      their treatment was 6.6 (+/- 5.08) years. There was no predominant opinion on
      sharing the information with the family, but there was a relationship between the
      opinions and psychopathology and personality. Regardless of the patients' mental
      state and personality, the opinions on the voluntary use of restraints and the
      use of restraints as punishment for intentionally aggressive behavior were mainly
      positive. The patients' opinions suggest a need for the implementation of more
      specific guidelines in the area of forensic psychiatry.

PMID- 24902819
TI  - A little slower, but just as good: postgraduate year resident versus attending
      outcomes in laparoscopic ventral hernia repair.
AB  - INTRODUCTION: The purpose of this study was to analyze the effect of residents on
      patient outcomes in laparoscopic ventral hernia repair (LVHR).We hypothesized
      that increasing postgraduate year (PGY) level would correlate with better
      outcomes. METHODS: The American College of Surgeons National Surgical Quality
      Improvement Program database was queried from 2005 to 2011 for elective LVHR.
      Attending only cases were used as the control, and resident cases were stratified
      into junior (PGY 1-3), chief (4-5), and fellow (6+) cases. Standard statistical
      tests and multivariate regression controlling for age, body mass index, Charlson
      comorbidity index, smoking, functional status, and inpatient cases were performed
      for trainee involvement and PGY level. RESULTS: There were 6,841 ventral hernia
      repairs that met inclusion criteria: 2,773 attending and 4,068 resident cases.
      There were 1,644 junior, 1,983 chief, and 441 fellow cases. Patients were similar
      between the attending and resident groups. The resident group had a higher rate
      of inpatient cases, general complications, longer operative time, and hospital
      length of stay. After controlling for confounders in multivariate analysis, only
      operative time was significantly different; resident cases were 17.7 min longer
      (CI 15.0-20.6; p < 0.001). There was no significant difference in the rate of
      wound or major complications, readmission, reoperation, or mortality between
      attending and resident cases. Demographics were not significantly different
      between the PGY level strata. On multivariate regression by PGY level with
      attending alone as the reference, only operative time was significantly
      different. Juniors (15.7 min, CI 12.2-19.2), chiefs (18.0 min, CI 14.7-21.3), and
      fellows (24.9 min, CI 19.1-30.7) had significantly longer cases than attending
      alone; all p < 0.001. CONCLUSION: Trainee involvement during LVHR does not change
      the clinical outcomes for patients as compared to those performed by an attending
      only. Operative time is significantly longer with increasing PGY level, perhaps
      indicating the complexity of the operation or increasing trainee involvement as
      primary surgeon. However, patient care does not suffer, affirming the current
      surgical training curriculum is appropriate.

PMID- 24902821
TI  - Luminescence in Sr4 Al14 O25 :Ce(3+) aluminate phosphor.
AB  - Cerium-doped Sr4 Al14 O25 phosphor is prepared using a single-step combustion
      synthesis and its X-ray diffraction (XRD), scanning electron microscopy (SEM),
      photoluminescence (PL) and thermoluminescence (TL) properties are characterized.
      XRD reveals the formation of the desired phase in the prepared sample. SEM
      micrographs of the prepared Sr4 Al14 O25 phosphor show that the particle size is
      10 um. The prepared Sr4 Al14 O25 , along with Sr4 Al14 O25 :Cex (x = 0.5-5 mol%)
      shows a PL emission peak at 314 nm under UV excitation of 262 nm wavelength due
      to 5d -> 4f transition. The phosphor is suitable for higher concentrations of Ce
      ions. The TL glow peak reveals three clearly visible distinct peaks at
      temperatures around 130, 231 and 336oC. The three peaks are separated by
      deconvolution and kinetic parameters calculated using Chen's peak shape method.
      The calculation shows that the reaction follows second-order kinetics with
      activation energy (E) values of 0.52, 0.81 and 1.12 eV, and frequency factor (s)
      values of 5.58 * 10(5) , 4.53 * 10(7) and 4.57 * 10(8) s(-1) for the three
      individual peaks.

PMID- 24902822
TI  - Family functioning in two treatments for adolescent anorexia nervosa.
AB  - OBJECTIVE: Family functioning impairment is widely reported in the eating
      disorders literature, yet few studies have examined the role of family
      functioning in treatment for adolescent anorexia nervosa (AN). This study
      examined family functioning in two treatments for adolescent AN from multiple
      family members' perspectives. METHOD: Participants were 121 adolescents with AN
      ages 12-18 from a randomized-controlled trial comparing family-based treatment
      (FBT) to individual adolescent-focused therapy (AFT). Multiple clinical
      characteristics were assessed at baseline. Family functioning from the
      perspective of the adolescent and both parents was assessed at baseline and after
      1 year of treatment. Full remission from AN was defined as achieving both weight
      restoration and normalized eating disorder psychopathology. RESULTS: In general,
      families dealing with AN reported some baseline impairment in family functioning,
      but average ratings were only slightly elevated compared to published impaired
      functioning cutoffs. Adolescents' perspectives on family functioning were the
      most impaired and were generally associated with poorer psychosocial functioning
      and greater clinical severity. Regardless of initial level of family functioning,
      improvements in several family functioning domains were uniquely related to full
      remission at the end of treatment in both FBT and AFT. However, FBT had a more
      positive impact on several specific aspects of family functioning compared to
      AFT. DISCUSSION: Families seeking treatment for adolescent AN report some
      difficulties in family functioning, with adolescents reporting the greatest
      impairment. Although FBT may be effective in improving some specific aspects of
      family dynamics, remission from AN was associated with improved family dynamics,
      regardless of treatment type.

PMID- 24902823
TI  - Endogenous cannabinoid anandamide impairs cell growth and induces apoptosis in
      chondrocytes.
AB  - Endocannabinoids has been described to be involved in articular degenerative
      disease by modulating nociception and immune system. However, the role of the
      endocannabinoid anandamide on chondrocyte cell viability is still unclear.
      Therefore, we decided to study anandamide's effects on chondrocytes viability and
      to evaluate its interactions with the catabolic factor TNF (tumor necrosis
      factor). Chondrocyte vitality was evaluated by MTT assay. We investigated LDH
      release, chromatin condensation, cleavage of focal adhesion kinase (FAK), and
      caspases-3, 8, and 9 activation. c-MYC mRNA levels were determined by RT-PCR. We
      studied by Western blot the activation patterns of AKT, AMPK, ERK, p38, and JNK
      kinases. Finally, we evaluate the effect of anandamide in TNF-induced caspase-3
      cleavage. Anandamide decreased chondrocyte vitality independently of its
      receptors. It induced AMPK activation without LDH release. Anandamide induced
      chromatin condensation, activation of caspase-3, 8, and 9, and FAK cleavage.
      Surprisingly, despite anandamide inhibited cell proliferation, it increased c-MYC
      expression. Moreover anandamide inhibited AKT activation, whilst it induced a
      sustained activation of ERK, JNK, and p38. Finally, anandamide synergized with
      TNF-alpha in the cleavage of caspase-3. In conclusion, our findings suggest that
      anandamide, alone or in combination with TNF-alpha, may be a potential
      destructive agent in cartilage.

PMID- 24902824
TI  - Identification of critical parameters in liquid enzyme-catalyzed biodiesel
      production.
AB  - CalleraTM Trans L, a liquid formulation of Thermomyces lanuginosus lipase, has
      recently shown great promise as a cost-efficient catalyst for methanolysis of
      triglyceride substrates, specifically in the BioFAME process. However,
      identifying the right combination of temperature and concentrations of catalyst,
      water and methanol to realize the full potential of the reaction system has
      remained a challenge. This study presents an investigation of the impact of
      temperature, enzyme and water concentration on the reaction, as well as the
      effect of methanol feed rate for the conversion of rapeseed oil in a fed-batch
      reaction system. It was observed that the reaction can be divided into two
      distinct parts. The first part of the reaction, during which primarily tri- and
      diglycerides are converted, proceeded at a high rate and thus required a high
      rate of methanol supply. The second part of the reaction, where the remaining di-
      and monoglycerides are converted, proceeded at a much lower rate. Consequently,
      it is necessary to reduce the methanol feed rate during the latter part of the
      reaction to avoid inhibition or even inactivation of the enzyme. Since the second
      part of the reaction occupied most of the 24-h reaction time, it was concluded
      that this is the part of the process where further development efforts should be
      targeted. This point was demonstrated by partially substituting the catalyst with
      a lipase with a different specificity, which enhanced the performance during the
      second phase of the reaction.

PMID- 24902827
TI  - Foodomics: the necessary route to boost quality, safety and bioactivity of foods.

PMID- 24902831
TI  - Nanosecond intersystem crossing times in fullerene acceptors: implications for
      organic photovoltaic diodes.
AB  - Triplet-exciton formation through intersystem crossing of photogenerated singlet
      excitons in fullerene acceptors can compete with charge generation in organic
      photovoltaic diodes. This article reports the intersystem crossing timescale
      (tauISC ) of the most commonly used fullerene acceptors, PC60 BM and PC70 BM, in
      solutions and in spin-coated films. These times are on the nanosecond timescale,
      and are longer than the characteristic times for charge generation (taud ). 

PMID- 24902832
TI  - The evolution of vision.
AB  - In this review, the evolution of vision is retraced from its putative origins in
      cyanobacteria to humans. Circadian oscillatory clocks, phototropism, and
      phototaxis require the capability to detect light. Photosensory proteins allow us
      to reconstruct molecular phylogenetic trees. The evolution of animal eyes leading
      from an ancestral prototype to highly complex image forming eyes can be
      deciphered on the basis of evolutionary developmental genetic experiments and
      comparative genomics. As all bilaterian animals share the same master control
      gene, Pax6, and the same retinal and pigment cell determination genes, we
      conclude that the different eye-types originated monophyletically and
      subsequently diversified by divergent, parallel, or convergent evolution. 

PMID- 24902833
TI  - Morphogenesis of simple leaves: regulation of leaf size and shape.
AB  - Plants produce new organs throughout their life span. Leaves first initiate as
      rod-like structures protruding from the shoot apical meristem, while they need to
      pass through different developmental stages to become the flat organ specialized
      in photosynthesis. Leaf morphogenesis is an active process regulated by many
      genes and pathways that can generate organs with a wide variety of sizes and
      shapes. Important differences in leaf architecture can be seen among different
      species, but also in single individuals. A key aspect of leaf morphogenesis is
      the precise control of cell proliferation. Modification or manipulation of this
      process may lead to leaves with different sizes and shapes, and changes in the
      organ margins and curvature. Many genes required for leaf development have been
      identified in Arabidopsis thaliana, and the mechanisms underlying leaf
      morphogenesis are starting to be unraveled at the molecular level. 

PMID- 24902834
TI  - Morphogenetic movements in the neural plate and neural tube: mouse.
AB  - The neural tube (NT), the embryonic precursor of the vertebrate brain and spinal
      cord, is generated by a complex and highly dynamic morphological process. In
      mammals, the initially flat neural plate bends and lifts bilaterally to generate
      the neural folds followed by fusion of the folds at the midline during the
      process of neural tube closure (NTC). Failures in any step of this process can
      lead to neural tube defects (NTDs), a common class of birth defects that occur in
      approximately 1 in 1000 live births. These severe birth abnormalities include
      spina bifida, a failure of closure at the spinal level; craniorachischisis, a
      failure of NTC along the entire body axis; and exencephaly, a failure of the
      cranial neural folds to close which leads to degeneration of the exposed brain
      tissue termed anencephaly. The mouse embryo presents excellent opportunities to
      explore the genetic basis of NTC in mammals; however, its in utero development
      has also presented great challenges in generating a deeper understanding of how
      gene function regulates the cell and tissue behaviors that drive this highly
      dynamic process. Recent technological advances are now allowing researchers to
      address these questions through visualization of NTC dynamics in the mouse embryo
      in real time, thus offering new insights into the morphogenesis of mammalian NTC.

PMID- 24902835
TI  - Generating mosaics for lineage analysis in flies.
AB  - By generating and studying mosaic organisms, we are learning how intricate
      tissues form as cells proliferate and diversify through organism development.
      FLP/FRT-mediated site-specific mitotic recombination permits the generation of
      mosaic flies with efficiency and control. With heat-inducible or tissue-specific
      FLP transgenes at our disposal, we can engineer mosaics carrying clones of
      homozygous cells that come from specific pools of heterozygous precursors. This
      permits detailed cell lineage analysis followed by mosaic analysis of gene
      functions in the underlying developmental processes. Expression of transgenes
      (e.g., reporters) only in the homozygous cells enables mosaic analysis in the
      complex nervous system. Tracing neuronal lineages by using mosaics revolutionized
      mechanistic studies of neuronal diversification and differentiation, exemplifying
      the power of genetic mosaics in developmental biology. 

PMID- 24902836
TI  - Mass spectrometry-driven phosphoproteomics: patterning the systems biology
      mosaic.
AB  - Protein phosphorylation is the best-studied posttranslational modification and
      plays a role in virtually every biological process. Phosphoproteomics is the
      analysis of protein phosphorylation on a proteome-wide scale, and mainly uses the
      same instrumentation and analogous strategies as conventional mass spectrometry
      (MS)-based proteomics. Measurements can be performed either in a discovery-type,
      also known as shotgun mode, or in a targeted manner which monitors a set of a
      priori known phosphopeptides, such as members of a signal transduction pathway,
      across biological samples. Here, we delineate the different experimental levels
      at which measures can be taken to optimize the scope, reliability, and
      information content of phosphoproteomic analyses. Various chromatographic and
      chemical protocols exist to physically enrich phosphopeptides from proteolytic
      digests of biological samples. Subsequent mass spectrometric analysis revolves
      around peptide ion fragmentation to generate sequence information and identify
      the backbone sequence of phosphopeptides as well as the phosphate group
      attachment site(s), and different modes of fragmentation like collision-induced
      dissociation (CID), electron transfer dissociation (ETD), and higher energy
      collisional dissociation (HCD) have been established for phosphopeptide analysis.
      Computational tools are important for the identification and quantification of
      phosphopeptides and mapping of phosphorylation sites, the deposition of large
      scale phosphoproteome datasets in public databases, and the extraction of
      biologically meaningful information by data mining, integration with other data
      types, and descriptive or predictive modeling. Finally, we discuss how orthogonal
      experimental approaches can be employed to validate newly identified
      phosphorylation sites on a biochemical, mechanistic, and physiological level. 

PMID- 24902839
TI  - Infrared thermography for monitoring of freeze-drying processes: instrumental
      developments and preliminary results.
AB  - Coupling an infrared (IR) camera to a freeze dryer for on-line monitoring of
      freeze-drying cycles is described for the first time. Normally, product
      temperature is measured using a few invasive Pt-100 probes, resulting in poor
      spatial resolution. To overcome this, an IR camera was placed on a process-scale
      freeze dryer. Imaging took place every 120 s through a Germanium window
      comprising 30,000 measurement points obtained contact-free from -40  degrees C to
      25  degrees C. Results are presented for an empty system, bulk drying of cheese
      slurry, and drying of 1 mL human serum in 150 vials. During freezing of the empty
      system, differences of more than 5  degrees C were measured on the shelf. Adding
      a tray to the empty system, a difference of more than 8  degrees C was observed.
      These temperature differences probably cause different ice structures affecting
      the drying speed during sublimation. A temperature difference of maximum 13 
      degrees C was observed in bulk mode during sublimation. When drying in vials,
      differences of more than 10  degrees C were observed. Gradually, the large
      temperature differences disappeared during secondary drying and products were
      transformed into uniformly dry cakes. The experimental data show that the IR
      camera is a highly versatile on-line monitoring tool for different kinds of
      freeze-drying processes.

PMID- 24902838
TI  - Regulation of the seed to seedling developmental phase transition by the LAFL and
      VAL transcription factor networks.
AB  - In the seed, a fundamental transition between embryo and vegetative phases of
      plant development is coordinated by the interaction between the AFL and VAL sub
      clades of the plant specific B3 domain transcription factor family. The AFL B3
      factors together with LEC1-type HAP3 transcription factors promote embryo
      maturation; whereas the VAL B3 factors repress the LEC1/AFL (LAFL) network during
      seed germination. Recent advances reveal that genes in key developmental programs
      and hormone signaling pathways are downstream targets of the LAFL network
      highlighting the central role of the LAFL network in integration of intrinsic
      developmental and hormonal signals during plant development. The VAL B3 proteins
      are proposed to mediate repression by recruiting a histone deacetylase complex
      (HDAC) to LAFL genes that contain the Sph/RY cis-element recognized by AFL and
      VAL B3-DNA-binding domains. In addition to VAL B3 factors, epigenetic mechanisms
      are implicated in maintaining repression of LAFL network during vegetative
      development. 

PMID- 24902842
TI  - Patient-centred care in general dental practice--a systematic review of the
      literature.
AB  - BACKGROUND: Delivering improvements in quality is a key objective within most
      healthcare systems, and a view which has been widely embraced within the NHS in
      the United Kingdom. Within the NHS, quality is evaluated across three key
      dimensions: clinical effectiveness, safety and patient experience, with the
      latter modelled on the Picker Principles of Patient-Centred Care (PCC). Quality
      improvement is an important feature of the current dental contract reforms in
      England, with "patient experience" likely to have a central role in the
      evaluation of quality. An understanding and appreciation of the evidence
      underpinning PCC within dentistry is highly relevant if we are to use this as a
      measure of quality in general dental practice. METHODS: A systematic review of
      the literature was undertaken to identify the features of PCC relevant to
      dentistry and ascertain the current research evidence base underpinning its use
      as a measure of quality within general dental practice. RESULTS: Three papers
      were identified which met the inclusion criteria and demonstrated the use of
      primary research to provide an understanding of the key features of PCC within
      dentistry. None of the papers identified were based in general dental practice
      and none of the three studies sought the views of patients. Some distinct
      differences were noted between the key features of PCC reported within the dental
      literature and those developed within the NHS Patient Experience Framework.
      CONCLUSIONS: This systematic review reveals a lack of understanding of PCC within
      dentistry, and in particular general dental practice. There is currently a poor
      evidence base to support the use of the current patient reported outcome measures
      as indicators of patient-centredness. Further research is necessary to understand
      the important features of PCC in dentistry and patients' views should be central
      to this research.

PMID- 24902837
TI  - The developmental control of size in insects.
AB  - The mechanisms that control the sizes of a body and its many parts remain among
      the great puzzles in developmental biology. Why do animals grow to a species
      specific body size, and how is the relative growth of their body parts controlled
      to so they grow to the right size, and in the correct proportion with body size,
      giving an animal its species-characteristic shape? Control of size must involve
      mechanisms that somehow assess some aspect of size and are upstream of mechanisms
      that regulate growth. These mechanisms are now beginning to be understood in the
      insects, in particular in Manduca sexta and Drosophila melanogaster. The control
      of size requires control of the rate of growth and control of the cessation of
      growth. Growth is controlled by genetic and environmental factors. Insulin and
      ecdysone, their receptors, and intracellular signaling pathways are the principal
      genetic regulators of growth. The secretion of these growth hormones, in turn, is
      controlled by complex interactions of other endocrine and molecular mechanisms,
      by environmental factors such as nutrition, and by the physiological mechanisms
      that sense body size. Although the general mechanisms of growth regulation appear
      to be widely shared, the mechanisms that regulate final size can be quite
      diverse. 

PMID- 24902843
TI  - Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on
      human colon adenocarcinoma.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) pathway is involved in
      primary tumor progression and in promoting metastasis in a considerable
      proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage
      of TGF-beta pathway signaling via an inhibitor could be a valuable tool in CRC
      treatment. METHODS: To evaluate the efficacy of systemic targeting of the TGF
      beta pathway for therapeutic effects on CRC, we investigated the effects of a
      TGbetaRI (TGF-beta receptor 1) or TbetaRI kinase inhibitor, SD-208, on SW-48,
      colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied
      by methyl thiazolyl tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays.
      Also, the histopathological and immunohistochemical evaluations were conducted by
      hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively.
      RESULTS: Our results showed no significant reduction in cell proliferation and
      vessel formation (170 +/- 70 and 165 +/- 70, P > 0.05) in treated SW-48 cells
      with SD-208 compared to controls. CONCLUSION: Our data suggested that SD-208
      could not significantly reduce tumor growth and angiogenesis in human colorectal
      cancer model at least using SW-48 cells.

PMID- 24902844
TI  - Identification of compounds that selectively target highly chemotherapy
      refractory neuroblastoma cancer stem cells.
AB  - Relapse of cancer months or years after an apparently successful therapy is
      probably caused by cancer stem cells (CSCs) due to their intrinsic features like
      dormant periods, radiorefraction, and acquired multidrug resistance (MDR)
      phenotypes, among other mechanisms of cellular drug evasiveness. Thus, the lack
      of currently efficacious interventions remains a major problem in the treatment
      of malignancies, together with the inability of existing drugs to destroy
      specifically CSCs. Neuroblastomas per se are highly chemotherapy-refractory
      extracranial tumors in infants with very low survival rates. So far, no effective
      cytostatics against this kind of tumors are clinically available. Therefore, we
      have put much effort into the development of agents to efficiently combat this
      malignancy. For this purpose, we tested several compounds isolated from Cuban
      propolis on induced CSCs (iCSC) derived from LAN-1 neuroblastoma cells which
      expressed several characteristics of tumor-initiating cells both in in-vitro and
      in-vivo models. Some small molecules such as flavonoids and polycyclic
      polyprenylated acylphloroglucinols (PPAP) were isolated using successive RT-HPLC
      cycles and identified employing mass spectrometry and NMR spectroscopic
      techniques. Their cytotoxicity was first screened in sensitive cell systems by
      MTT proliferation assays and afterwards studied in less sensitive neuroblastoma
      iCSC models. We found several compounds with considerable anti-iCSC activity,
      most of them belonging to the PPAP class. The majority of the compounds act in a
      pleiotropic manner on the molecular biology of tumors although their specific
      targets remain unclear. Nevertheless, two substances, one of them a flavonoid,
      induced a strong disruption of tubulin polymerization. In addition, an unknown
      compound strongly inhibited replicative enzymes like toposimerases I/II and DNA
      polymerase. Here, we report for the first time cytotoxic activities of small
      molecules isolated from Caribbean propolis which could be promising therapeutics
      or lead structures against therapy-refractory neuroblastoma entities.
      *Contributed equally. 

PMID- 24902846
TI  - The management of lichen sclerosus in a genitourinary medicine setting: a 12
      month retrospective case-notes review.
AB  - A retrospective case-notes review was undertaken of all women with lichen
      sclerosus seen during a 12-month period to review their characteristics and care.
      A total of 273 case-notes were reviewed. The mean age was 61 years (range, 14
      94), and the mean duration of symptoms was 6.4 years (range, 1-50). The mean age
      at diagnosis was 55 years (range, 7-92). Sixty-two (23%) had at least one other
      autoimmune condition. Autoimmune conditions were seven times more frequent
      overall compared with United Kingdom prevalences. On-going symptoms were reported
      as none/minimal in 196 (72%), moderate in 65 (24%) and severe in 12 (4%). A total
      of 233 women (85%) had on-going treatment with clobetasol propionate (Dermovate)
      ointment with a mode of eight applications per month (range, 0-30). Forty-three
      women (16%) reported sexual dysfunction and 13 (5%) had needed at least one
      surgical procedure to restore sexual function. Eighty-six (32%) had undergone at
      least one biopsy. Nine squamous cell cancers (3%) had been diagnosed in six women
      (2%). These patients were managed in line with all current guidance. It is
      surprising that there is still no evidence to direct long-term management. 

PMID- 24902845
TI  - Identification of longitudinally dynamic biomarkers in Alzheimer's disease
      cerebrospinal fluid by targeted proteomics.
AB  - BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia affecting
      greater than 26 million people worldwide. Although cerebrospinal fluid (CSF)
      levels of Abeta42, tau, and p-tau181 are well established as diagnostic
      biomarkers of AD, there is a need for additional CSF biomarkers of neuronal
      function that continue to change during disease progression and could be used as
      pharmacodynamic measures in clinical trials. Multiple proteomic discovery
      experiments have reported a range of CSF biomarkers that differ between AD and
      control subjects. These potential biomarkers represent multiple aspects of the
      disease pathology. The performance of these markers has not been compared with
      each other, and their performance has not been evaluated longitudinally. RESULTS:
      We developed a targeted-proteomic, multiple reaction monitoring (MRM) assay for
      the absolute quantitation of 39 peptides corresponding to 30 proteins. We
      evaluated the candidate biomarkers in longitudinal CSF samples collected from
      aged, cognitively-normal control (n = 10), MCI (n = 5), and AD (n = 45)
      individuals (age > 60 years). We evaluated each biomarker for diagnostic
      sensitivity, longitudinal consistency, and compared with CSF Abeta42, tau, and p
      tau181. Four of 28 quantifiable CSF proteins were significantly different between
      aged, cognitively-normal controls and AD subjects including chitinase-3-like
      protein 1, reproducing published results. Four CSF markers demonstrated
      significant longitudinal change in AD: Amyloid precursor protein, Neuronal
      pentraxin receptor, NrCAM and Chromogranin A. Robust correlations were observed
      within some subgroups of proteins including the potential disease progression
      markers. CONCLUSION: Using a targeted proteomics approach, we confirmed previous
      findings for a subset of markers, defined longitudinal performance of our panel
      of markers, and established a flexible proteomics method for robust multiplexed
      analyses.

PMID- 24902848
TI  - Advocating for malaria elimination - learning from the successes of other
      infectious disease elimination programmes.
AB  - Malaria elimination is back on the agenda, but it remains challenging for
      countries to make the transition from effective control to elimination. Many
      other infectious diseases have been targeted by globally-coordinated elimination
      advocacy campaigns, and advocacy has been considered an essential component of
      the success of other disease elimination programmes. What can the malaria
      community learn from these successes? A review of infectious disease elimination
      programmes to identify successful elements of advocacy for disease elimination
      was undertaken. Key elements are: (i) a global elimination plan, supported by
      international health bodies; (ii) thorough costings and tools to support the
      business case; (iii) an approach that is positioned within a development
      framework; (iv) core elimination advocacy messages; (v) provision of advocacy
      tools for partners (vi) extensive and effective community engagement; and (vii)
      strong partnerships. These features provide insights into 'what works' in global
      elimination advocacy. Advocacy is a powerful tool to support the long-term
      political and financial commitment necessary for malaria elimination. The global
      malaria community needs to work together, to ensure that the early steps towards
      the end goal of malaria elimination are taken. 

PMID- 24902847
TI  - Targeted germ line disruptions reveal general and species-specific roles for
      paralog group 1 hox genes in zebrafish.
AB  - BACKGROUND: The developing vertebrate hindbrain is transiently segmented into
      rhombomeres by a process requiring Hox activity. Hox genes control specification
      of rhombomere fates, as well as the stereotypic differentiation of rhombomere
      specific neuronal populations. Accordingly, germ line disruption of the paralog
      group 1 (PG1) Hox genes Hoxa1 and Hoxb1 causes defects in hindbrain segmentation
      and neuron formation in mice. However, antisense-mediated interference with
      zebrafish hoxb1a and hoxb1b (analogous to murine Hoxb1 and Hoxa1, respectively)
      produces phenotypes that are qualitatively and quantitatively distinct from those
      observed in the mouse. This suggests that PG1 Hox genes may have species-specific
      functions, or that anti-sense mediated interference may not completely inactivate
      Hox function in zebrafish. RESULTS: Using zinc finger and TALEN technologies, we
      disrupted hoxb1a and hoxb1b in the zebrafish germ line to establish mutant lines
      for each gene. We find that zebrafish hoxb1a germ line mutants have a more severe
      phenotype than reported for Hoxb1a antisense treatment. This phenotype is similar
      to that observed in Hoxb1 knock out mice, suggesting that Hoxb1/hoxb1a have the
      same function in both species. Zebrafish hoxb1b germ line mutants also have a
      more severe phenotype than reported for hoxb1b antisense treatment (e.g. in the
      effect on Mauthner neuron differentiation), but this phenotype differs from that
      observed in Hoxa1 knock out mice (e.g. in the specification of rhombomere 5 (r5)
      and r6), suggesting that Hoxa1/hoxb1b have species-specific activities. We also
      demonstrate that Hoxb1b regulates nucleosome organization at the hoxb1a promoter
      and that retinoic acid acts independently of hoxb1b to activate hoxb1a
      expression. CONCLUSIONS: We generated several novel germ line mutants for
      zebrafish hoxb1a and hoxb1b. Our analyses indicate that Hoxb1 and hoxb1a have
      comparable functions in zebrafish and mouse, suggesting a conserved function for
      these genes. In contrast, while Hoxa1 and hoxb1b share functions in the formation
      of r3 and r4, they differ with regards to r5 and r6, where Hoxa1 appears to
      control formation of r5, but not r6, in the mouse, whereas hoxb1b regulates
      formation of r6, but not r5, in zebrafish. Lastly, our data reveal independent
      regulation of hoxb1a expression by retinoic acid and Hoxb1b in zebrafish.

PMID- 24902849
TI  - Key elements of the RNAi pathway are regulated by hepatitis B virus replication
      and HBx acts as a viral suppressor of RNA silencing.
AB  - The host-mediated RNAi pathways restrict replication of viruses in plant,
      invertebrate and vertebrate systems. However, comparatively little is known about
      the interplay between RNAi and various viral infections in mammalian hosts. We
      show in the present study that the siRNA-mediated silencing of Drosha, Dicer and
      Ago2 [argonaute RISC (RNA-induced silencing complex) catalytic component 2]
      transcripts in Huh7 cells resulted in elevated levels of HBV (hepatitis B virus)
      specific RNAs and, conversely, we observed a decrease in mRNA and protein levels
      of same RNAi components in HepG2 cells infected with HBV. Similar reductions were
      also detectable in CHB (chronic hepatitis B) patients. Analysis of CHB liver
      biopsy samples, with high serum HBV DNA load (>log108 IU/ml), revealed a reduced
      mRNA and protein levels of Drosha, Dicer and Ago2. The low expression levels of
      key RNAi pathway components in CHB patient samples as well as hepatic cells
      established a link between HBV replication and RNAi components. The HBV proteins
      were also examined for RSS (RNA-silencing suppressor) properties. Using GFP-based
      reversion of silencing assays, in the present study we found that HBx is an RSS
      protein. Through a series of deletions and substitution mutants, we found that
      the full-length HBx protein is required for optimum RSS activity. The in vitro
      dicing assays revealed that the HBx protein inhibited the human Dicer-mediated
      processing of dsRNAs into siRNAs. Together, our results suggest that the HBx
      protein might function as RSS to manipulate host RNAi defence, in particular by
      abrogating the function of Dicer. The present study may have implications in the
      development of newer strategies to combat HBV infection.

PMID- 24902850
TI  - Evaluation of the impact of transient interruption of antiangiogenic treatment
      using ultrasound-based techniques in a murine model of hepatocellular carcinoma.
AB  - BACKGROUND: Development of escape pathways from antiangiogenic treatments was
      reported to be associated with enhanced tumor aggressiveness and rebound effect
      was suggested after treatment stop. Aim of the study was to evaluate tumor
      response simulating different conditions of administration of antiangiogenic
      treatment (transient or definitive treatment stop) in a mouse model of
      hepatocellular carcinoma. METHODS: Subcutaneous tumors were created by
      inoculating 5 * 10(6) Huh7 cells into the right flank of 14 nude mice. When tumor
      size reached 5-10 mm, mice were divided in 3 groups: group 1 was treated with
      placebo, group 2 was treated with sorafenib (62 mg/kg via gavage) but temporarily
      suspended from day +5 to +9, whereas in group 3 sorafenib was definitively
      stopped at day +5. At day +13 all mice were sacrificed, collecting masses for
      Western-Blot analyses. Volume was calculated with B-mode ultrasonography at day
      0, +5, +9, +11 and +13. VEGFR2-targeted contrast-enhanced ultrasound using BR55
      (Bracco Imaging) was performed at day +5 and +13 and elastonosography (Esaote) at
      day +9 and +11 to assess tumor stiffness. RESULTS: Median growth percentage delta
      at day +13 versus day 0 was 197% (115-329) in group 1, 81% (48-144) in group 2
      and 111% (27-167) in group 3. Median growth delta at day +13 with respect to day
      +5 was 79% (48-127), 37% (-14128) and 81% (15-87) in groups 1, 2 and 3,
      respectively. Quantification of targeted-CEUS at day +13 showed higher values in
      group 3 (509 Arbitrary Units AI, range 293-652) than group 1 (275 AI, range 191
      494) and group 2 (181 AI, range 63-318) (p=0.033). Western-Blot analysis
      demonstrated higher VEGFR2 expression in group 3 with respect to group 1 and 2.
      CONCLUSIONS: A transient interruption of antiangiogenic treatment does not impede
      restoration of tumor response, while a definitive interruption tends to stimulate
      a rebound of angiogenesis to higher level than without treatment.

PMID- 24902851
TI  - Engineered cytidine triphosphate synthetase with reduced product inhibition.
AB  - Cytidine triphosphate (CTP) synthetase (CTPS) (EC number 6.3.4.2) is a key enzyme
      involved in de novo synthesis of CTP. It catalyzes the rate-limiting step of the
      process due to the product inhibition effects on the enzyme. In this study, a
      novel CTPS from Corynebacterium glutamicum ATCC 13032 (CgCTPS) was cloned,
      expressed and characterized. A series of mutagenesis in its N-terminal ammonia
      ligase (ALase) domain was performed in order to reduce CTP product inhibition.
      All single mutation variants (D160E, E162A, E168K) lowered product inhibition by
      lowering the enzyme's binding affinity for CTP. The homology model of CgCTPS
      showed that D160E mutant caused steric hindrance for the pyrimidine ring of CTP
      stacking, E162A disrupted the hydrogen bond between CTP ribose and side chain and
      D168K caused minor localized structure perturbations of CTP binding pocket. The
      triple mutant of CTPS (D160E-E162A-E168K) with halved Km, doubled Vmax and the
      23.5-fold increased IC50 for CTP shows a potential for use in industrial-scale
      CTP production by its better performance in enzyme kinetics and product
      inhibition. 

PMID- 24902852
TI  - Exams? Why worry? Interpreting anxiety as facilitative and stress appraisals.
AB  - BACKGROUND AND OBJECTIVES: The present study examined why people differ in how
      they appraise the same stressful situation (an approaching exam). DESIGN: We
      explored whether interpreting anxiety as a facilitative emotion can affect the
      type of stress appraisal people make. METHOD: One hundred and three undergraduate
      students took part in this study, which lasted for 10 days (leading up to an
      exam). The students completed a daily self-reported evaluation of anxiety,
      emotional exhaustion, and stress experienced. RESULTS: The findings suggest a
      process by which a stressful time can be experienced as motivating rather than
      threatening or emotionally exhausting. For example, interpreting anxiety as
      facilitative moderated the relationship between anxiety and stress appraisals.
      When interpreting their anxiety as facilitative, individuals showed a higher
      tendency to make challenge stress appraisals and a lower tendency to appraising
      the stressor as a threat. These differences were especially visible with high
      levels of anxiety. Furthermore, interpreting anxiety as facilitative was
      negatively associated with emotional exhaustion, but positively associated with
      the academic performance. CONCLUSIONS: These findings suggest an explanation why
      people differ in how they appraise the same stressor: how people interpret their
      anxiety may to a large part affect how they appraise difficult events and
      situations.

PMID- 24902853
TI  - Retroperitoneal fibrosis as the presenting manifestation of IgG4-related disease
      in a patient previously diagnosed with granulomatosis with polyangiitis
      (Wegener's): one disease or two?

PMID- 24902854
TI  - An analytical approach for flow analysis in aquifers with spatially varying top
      boundary.
AB  - Analytical models of groundwater flow with a spatially varying elevation of a top
      boundary are widely used. However, a vast majority of previous analytical studies
      truncated the irregularly shaped top section with little to no analyses of the
      shortcomings of the approximate solutions for the resulting rectangles or
      parallelepipeds. We present an analytical approach based on a perturbation
      technique that treats complete domains. It is especially accurate near the top
      boundary, where fluid circulation is most pronounced and higher accuracy is
      typically needed, such as in regional or hyporheic systems flow. The approach is
      illustrated by analyzing flow for a Tothian unit basin. 

PMID- 24902855
TI  - PAR1-dependent COX-2/PGE2 production contributes to cell proliferation via EP2
      receptors in primary human cardiomyocytes.
AB  - BACKGROUND AND PURPOSE: Different protease-activated receptors (PARs) activated
      by thrombin are involved in cardiovascular disease, via up-regulation of
      inflammatory proteins including COX-2. However, the mechanisms underlying
      thrombin-regulated COX-2 expression in human cardiomyocytes remain unclear.
      EXPERIMENTAL APPROACH: Human cardiomyocytes were used in the study. Thrombin
      induced COX-2 protein and mRNA expression, and signalling pathways were
      determined by Western blot, real-time PCR and COX-2 promoter luciferase reporter
      assays, and pharmacological inhibitors or siRNAs. PGE2 generation and cell
      proliferation were also determined. KEY RESULTS: Thrombin-induced COX-2 protein
      and mRNA expression, promoter activity and PGE2 release was attenuated by the
      PAR1 antagonist (SCH79797) or the inhibitors of proteinase activity (PPACK),
      MEK1/2 (U0126), p38 MAPK (SB202190) or JNK1/2 (SP600125), and transfection with
      small interfering RNA (siRNA) of PAR1, p38, p42 or JNK2. These results suggested
      that PAR1-dependent MAPKs participate in thrombin-induced COX-2 expression in
      human cardiomyocytes. Moreover, thrombin stimulated phosphorylation of MAPKs,
      which was attenuated by PPACK and SCH79797. Furthermore, thrombin-induced COX-2
      expression was blocked by the inhibitors of AP-1 (tanshinone IIA) and NF-kappaB
      (helenalin). Moreover, thrombin-stimulated phosphorylation of c-Jun/AP-1 and
      p65/NF-kappaB was attenuated by tanshinone IIA and helenalin, respectively,
      suggesting that thrombin induces COX-2 expression via PAR1/MAPKs/AP-1 or the NF
      kappaB pathway. Functionally, thrombin increased human cardiomyocyte
      proliferation through the COX-2/PGE2 system linking to EP2 receptors, as
      determined by proliferating cell nuclear antigen and cyclin D1 expression.
      CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that MAPKs-mediated
      activation of AP-1/NF-kappaB pathways is, at least in part, required for COX
      2/PGE2 /EP2 -triggered cell proliferation in human cardiomyocytes.

PMID- 24902857
TI  - In vitro evaluation of temperature changes in the root canal induced by
      ultrasonic scalers.
AB  - OBJECTIVE: To evaluate in vitro the thermal effects induced by four different
      ultrasonic scalers on the temperature in the root canal during ultrasonic
      scaling. METHODS: An extracted lower central incisor provided with a thermocouple
      in the root canal and a tube, entering the tooth incisally and exiting it
      apically to simulate an artificial bloodstream, was placed in a model of the
      lower jaw with soft artificial gingiva. Tested ultrasonic scaler systems
      included: EMS PM-600, Satelec P-max, Durr Vector and Dentsply Cavitron. The tooth
      was scaled with each system at full water supply of 21 degrees C. Furthermore,
      the amount of water supply was determined to maintain during scaling a constant
      temperature in the root canal. Finally, thermal changes due to scaling without
      water were assessed. RESULTS: Except for the Vector all scaler systems showed a
      temperature decrease in the root canal. The Vector with water/polish suspension
      showed a trend towards an increase in temperature. To maintain a constant
      temperature in the root canal the Cavitron needed twice the amount of water
      compared with PM-600 and P-max. Without water, all scaling systems induced a
      temperature increase. CONCLUSION: For safe ultrasonic scaling, care should be
      taken that the cooling water has room temperature and that, dependent on the
      scaler system, the proper amount of water is supplied.

PMID- 24902856
TI  - A comparison of two informative SNP-based strategies for typing Pseudomonas
      aeruginosa isolates from patients with cystic fibrosis.
AB  - BACKGROUND: Molecular typing is integral for identifying Pseudomonas aeruginosa
      strains that may be shared between patients with cystic fibrosis (CF). We
      conducted a side-by-side comparison of two P. aeruginosa genotyping methods
      utilising informative-single nucleotide polymorphism (SNP) methods; one targeting
      10 P. aeruginosa SNPs and using real-time polymerase chain reaction technology
      (HRM10SNP) and the other targeting 20 SNPs and based on the Sequenom MassARRAY
      platform (iPLEX20SNP). METHODS: An in-silico analysis of the 20 SNPs used for the
      iPLEX20SNP method was initially conducted using sequence type (ST) data on the P.
      aeruginosa PubMLST website. A total of 506 clinical isolates collected from
      patients attending 11 CF centres throughout Australia were then tested by both
      the HRM10SNP and iPLEX20SNP assays. Type-ability and discriminatory power of the
      methods, as well as their ability to identify commonly shared P. aeruginosa
      strains, were compared. RESULTS: The in-silico analyses showed that the 1401 STs
      available on the PubMLST website could be divided into 927 different 20-SNP
      profiles (D-value = 0.999), and that most STs of national or international
      importance in CF could be distinguished either individually or as belonging to
      closely related single- or double-locus variant groups. When applied to the 506
      clinical isolates, the iPLEX20SNP provided better discrimination over the
      HRM10SNP method with 147 different 20-SNP and 92 different 10-SNP profiles
      observed, respectively. For detecting the three most commonly shared Australian
      P. aeruginosa strains AUST-01, AUST-02 and AUST-06, the two methods were in
      agreement for 80/81 (98.8%), 48/49 (97.8%) and 11/12 (91.7%) isolates,
      respectively. CONCLUSIONS: The iPLEX20SNP is a superior new method for broader
      SNP-based MLST-style investigations of P. aeruginosa. However, because of
      convenience and availability, the HRM10SNP method remains better suited for
      clinical microbiology laboratories that only utilise real-time PCR technology and
      where the main interest is detection of the most highly-prevalent P. aeruginosa
      CF strains within Australian clinics.

PMID- 24902859
TI  - Socio-economic disadvantage and demographics as factors in stage of colorectal
      cancer presentation and survival.
AB  - BACKGROUND: Colorectal cancer (CRC) is common, and early diagnosis improves
      outcome. Overseas studies have suggested that low socio-economic status (SES) is
      related to advanced cancer stage at presentation and reduced survival. The
      situation in Australia is unclear. This study examines the effect of demographic
      and SES on CRC stage at presentation and survival in a single tertiary centre.
      METHODS: Patients undergoing surgical resection for CRC (1 January 2005 to 31
      December 2010) were identified, and socio-demographic and histopathological
      information obtained. Four socio-economic indices using 2006 Australian Census
      data were assigned by residential postcode. Factors contributing to tumour (T)
      and American Joint Committee on Cancer (AJCC) stage at presentation and survival
      were assessed. RESULTS: Five hundred and fifty-seven patients were included.
      Results did not support a relationship between SES and either advanced stage at
      presentation or survival. Only one index (economic resources) was related to a
      more advanced T stage at presentation (P = 0.011); none were related to AJCC
      stage or survival. No significant relationship was found between an individual's
      country of birth, language spoken, private insurance or employment status and
      presenting with a later T or AJCC stage. Age, AJCC and T stage at diagnosis and
      emergency presentation significantly affected survival on multivariate analysis.
      CONCLUSION: SES and most demographic factors did not appear to significantly
      influence CRC stage at presentation and outcome. A focus on obtaining equivalent
      access to health care both nationally and internationally could prove beneficial
      in improving outcomes for CRC.

PMID- 24902858
TI  - A systematic review of microRNA expression profiling studies in human gastric
      cancer.
AB  - Gastric cancer (GC) is the second leading cause of global cancer mortality. Most
      GC patients are diagnosed with advanced-stage disease and show extremely poor
      prognosis. All of the GC research has a common interest to search for the
      specific and sensitive biomarkers for early diagnosis of GC. Number of microRNAs
      play important role in GC. We carried out a systematic review of published miRNA
      profiling studies that compared the miRNA expression profiles between GC tissues
      and paired noncancerous gastric tissue. A vote-counting strategy was followed
      with the collection of information like total number of studies reporting
      differential expression of miRNA, total number of tissue samples used in the
      studies, direction of differential expression and fold change. A total of 352
      differentially expressed microRNAs were reported in the 14 microRNA expression
      profiling studies that compared GC tissues with normal tissues with 120 microRNAs
      reported at least in two studies. In the group of consistently reported
      microRNAs, miR-21 was reported upregulated in 10 studies followed by miR-25, miR
      92, and miR-223 upregulated in eight studies. MiR-375 and miR-148a were found
      downregulated in six and five studies, respectively, followed by miR-638 in four
      studies. MiR-107 and miR-103 were reported in nine and eight studies,
      respectively, but their expression were inconsistent. From this study, the most
      consistently reported upregulated microRNA was found to be miR-21. This
      systematic review study of human GC microRNA expression profiling studies would
      provide information on microRNAs with potential role as the biomarkers in gastric
      cancer. 

PMID- 24902860
TI  - Details of "never" events should be generally accessible.

PMID- 24902861
TI  - Dedicated 'cannabis only' treatment clinics in New South Wales, Australia: client
      and treatment characteristics and associations with first-time treatment seeking.
AB  - INTRODUCTION AND AIMS: Over the past decade, there has been significant
      investment in dedicated cannabis-only treatment clinics in New South Wales. This
      study aims to describe the characteristics of clients and compares first-time
      treatment seeking history and treatment completion rates between dedicated and
      non-dedicated clinics. DESIGN AND METHODS: An observational study of
      administrative information from 209,012 drug and alcohol treatment episodes from
      services reporting to the New South Wales Alcohol and Other Drug Treatment
      Services Minimum Dataset, July 2003-June 2008. RESULTS: Across all episodes,
      cannabis was the second most prevalent primary drug of concern (17.8%, n =
      37,242). The majority of clients primarily seeking treatment for cannabis were
      male (69.4%, 26,088), with a mean age of 29 years. Counselling was the most
      common cannabis treatment (34.1%, n = 12,713), with 11.6% (n = 1476) of those
      receiving counselling having done so at a cannabis clinic. Those treated in
      cannabis clinics were older (30.12 years vs. 27.95 years; P < 0.0001); had
      shorter episode durations (10.95 weeks vs. 12.71 weeks; P < 0.0001); and were
      more likely to be naive to treatment (53.7% vs. 47.7%; P < 0.0001). Indigenous
      Australian treatment seekers were more likely to complete cannabis treatment in a
      dedicated cannabis clinic (49.6%) than in a non-dedicated clinic (40.5%; P <
      0.05). DISCUSSION AND CONCLUSION: Cannabis clinics have attracted groups
      traditionally difficult to attract and retain in treatment. As the cohort of
      daily cannabis users age, it is important that service models are attractive to
      older clients, new to treatment. Rigorous, prospective research examining client
      treatment outcomes are now warranted.

PMID- 24902862
TI  - Absence of gender-based differences in the atrial and pulmonary vein substrate: a
      detailed electroanatomic mapping study.
AB  - BACKGROUND: Gender-based differences in the clinical nature of cardiac
      arrhythmias such as atrial fibrillation (AF) are well established. OBJECTIVE: The
      purpose of this study was to identify any such gender-based differences in the
      underlying pulmonary vein and atrial substrate. METHODS AND RESULTS: Thirty-eight
      patients with no history of AF undergoing catheter ablation for supraventricular
      tachycardia (SVT) and 55 with paroxysmal or persistent AF undergoing catheter
      ablation of AF underwent detailed electroanatomic mapping of the pulmonary veins
      and atria. Refractory periods in multiple locations, sinus node function,
      endocardial bipolar voltage, pulmonary vein and atrial conduction, and bipolar
      electrogram complexity were analyzed. There were no significant between-gender
      differences in age or other clinical variables known to impact on the atrial or
      pulmonary vein substrate. In neither the AF nor the non-AF cohorts were there any
      significant differences in atrial or pulmonary vein refractoriness, sinus node
      function, any measure of PV electrophysiology, or any measure of atrial
      electrophysiology. CONCLUSION: No systematic between-gender differences were
      observed in the PV or atrial substrate either in those with or without a history
      of AF, with a similar prevalence of the cardiovascular comorbidities frequently
      associated with atrial remodeling and AF seen in both male and female groups.

PMID- 24902863
TI  - Characterization of occupational exposure to air contaminants in modern
      tunnelling operations.
AB  - OBJECTIVES: Personal air measurements of aerosols and gases among tunnel
      construction workers were performed as part of a 11-day follow-up study on the
      relationship between exposure to aerosols and gases and cardiovascular and
      respiratory effects. METHODS: Ninety tunnel construction workers employed at 11
      available construction sites participated in the exposure study. The workers were
      divided into seven job groups according to tasks performed. Exposure measurements
      were carried out on 2 consecutive working days prior to the day of health
      examination. Summary statistics were computed using maximum likelihood estimation
      (MLE), and the procedure NLMIXED and LIFEREG in SAS was used to perform MLE for
      repeated measures data subject to left censoring and for calculation of within-
      and between-worker variance components. RESULTS: The geometric mean (GM) air
      concentrations for the thoracic mass aerosol sub-fraction, alpha-quartz, oil
      mist, organic carbon (OC), and elemental carbon (EC) for all workers were 561,
      63, 210, 146, and 35.2 MUg m(-3), respectively. Statistical differences of air
      concentrations between job groups were observed for all contaminants, except for
      OC, EC, and ammonia (P > 0.05). The shaft drillers, injection workers, and
      shotcreting operators were exposed to the highest GM levels of thoracic dust
      (7061, 1087, and 865 MUg m(-) (3), respectively). The shaft drillers and the
      support workers were exposed to the highest GM levels of alpha-quartz (GM = 844
      and 118 MUg m(-3), respectively). Overall, the exposure to nitrogen dioxide and
      ammonia was low (GM = 120 and 251 MUg m(-) (3), respectively). CONCLUSIONS:
      Findings from this study show significant differences between job groups with
      shaft drilling as the highest exposed job to air concentrations for all measured
      contaminants. Technical interventions in this job should be implemented to reduce
      exposure levels. Overall, diesel exhaust air concentrations seem to be lower than
      previously assessed (as EC).

PMID- 24902864
TI  - Aspirin influences megakaryocytic gene expression leading to up-regulation of
      multidrug resistance protein-4 in human platelets.
AB  - AIM: The aim of the study was to investigate whether human megakaryocytic cells
      have an adaptive response to aspirin treatment, leading to an enhancement of
      multidrug resistance protein-4 (MRP4) expression in circulating platelets
      responsible for a reduced aspirin action. We recently found that platelet MRP4
      overexpression has a role in reducing aspirin action in patients after by-pass
      surgery. Aspirin enhances MRP4-mRNA levels in rat liver and drug administration
      transcriptionally regulates MRP4 gene expression through peroxisome proliferator
      activated receptor-alpha (PPARalpha). METHODS: The effects induced by aspirin or
      PPARalpha agonist (WY14643) on MRP4 modulation were evaluated in vitro in a human
      megakaryoblastic DAMI cell line, in megakaryocytes (MKs) and in platelets
      obtained from human haematopoietic progenitor cell (HPC) cultures, and in vivo
      platelets obtained from aspirin treated healthy volunteers (HV). RESULTS: In DAMI
      cells, aspirin and WY14643 treatment induced a significant increase in MRP4 and
      PPARalpha expression. In human MKs grown in the presence of either aspirin or
      WY14643, MRP4 and PPARalpha-mRNA were higher than in control cultures and derived
      platelets showed an enhancement in MRP4 protein expression. The ability of
      aspirin to modulate MRP4 expression in MKs and to transfer it to platelets was
      also confirmed in vivo. In fact, we found the highest MRP4 mRNA and protein
      expression in platelets obtained from HV after 15 days' aspirin treatment.
      CONCLUSIONS: The present study provides evidence, for the first time, that
      aspirin treatment affects the platelet protein pattern through MK genomic
      modulation. This work represents an innovative and attractive approach, useful
      both to identify patients less sensitive to aspirin and to improve
      pharmacological treatment in cardiovascular high-risk patients.

PMID- 24902865
TI  - The pivotal role of the supplementary motor area in startle epilepsy as
      demonstrated by SEEG epileptogenicity maps.
AB  - Startle seizures belong to reflex epilepsy syndromes. They usually occur in
      patients with mental deficiency and showing widely extended cortical lesions,
      often involving the sensorimotor area. Here we report three cases who did not
      fulfill these criteria, and in whom stereotactic electroencephalography (SEEG)
      recordings demonstrated the prominent involvement of the supplementary motor area
      (SMA). Visual analysis was complemented by time-frequency analysis of SEEG
      signals using a neuroimaging approach (Epileptogenicity Maps), which showed at
      seizure onset a significant increase of high frequency oscillations (HFOs, 60-100
      Hz) over the premotor and prefrontal areas. Critically, in all cases, the SMA
      showed ictal HFOs at seizure onset and was included in the surgical resection.
      All patients became seizure-free after surgery, and histopathological
      examinations showed no specific lesion. These cases suggest the prominent but not
      exclusive role of SMA in startle seizures, and highlight the fact that surgery
      can be considered even in the absence of any magnetic resonance imaging (MRI)
      lesion.

PMID- 24902866
TI  - Intracavernous delivery of stromal vascular fraction restores erectile function
      through production of angiogenic factors in a mouse model of cavernous nerve
      injury.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a major complication of radical
      prostatectomy. Men with radical prostatectomy-induced ED respond less positively
      to oral phosphodiesterase-5 inhibitors. AIM: The study aims to examine whether
      and how stromal vascular fraction (SVF) restores erectile function in mice with
      cavernous nerve injury (CNI). METHODS: Twelve-week-old male C57BL/6J mice were
      used and the animals were distributed into five groups: sham operation group and
      CNI group receiving a single intracavernous injection of phosphate-buffered
      saline (PBS) or SVF (1 * 10(4) , 1 * 10(5) , or 3 * 10(5) cells/20 MUL,
      respectively). SVF was isolated from epididymal adipose tissues of green
      fluorescence protein transgenic mice. MAIN OUTCOME MEASURES: Two weeks after
      injection, erectile function was measured by cavernous nerve stimulation. The
      penis was stained with antibodies to platelet/endothelial cell adhesion molecule
      1, phosphohistone H3, and phosphorylated endothelial nitric oxide synthase
      (phospho-eNOS). We also performed Western blot for angiopoietin-1 (Ang-1),
      vascular endothelial growth factor-A, hepatocyte growth factor, phospho-eNOS, and
      eNOS in the corpus cavernosum tissue. RESULTS: Local delivery of SVF restored
      erectile function in a dose-dependent manner in CNI mice. The highest erectile
      response was noted at a dose of 3 * 10(5) cells, for which the response was
      comparable with that in the sham operation group. Local delivery of SVF
      significantly increased the expression of angiogenic factor proteins and induced
      cavernous endothelial cell proliferation and eNOS phosphorylation compared with
      that in the PBS-treated CNI group. SVF-induced promotion of cavernous
      angiogenesis and erectile function was diminished in the presence of soluble
      antibody to Tie2, a receptor tyrosine kinase of Ang-1. CONCLUSION: Secretion of
      angiogenic factors from SVF is an important mechanism by which SVF induces
      cavernous endothelial regeneration and restores erectile function. These findings
      suggest that cavernous endothelial regeneration by using SVF may represent a
      promising treatment strategy for radical prostatectomy-induced ED.

PMID- 24902867
TI  - 'Double trouble': diagnostic challenges in genetic skin disorders.

PMID- 24902868
TI  - Open prospective study of ziprasidone in patients with schizophrenia with
      depressive symptoms: a multicenter study.
AB  - AIMS: The goal of this study was to examine the efficacy and safety of
      ziprasidone to treat depressive symptoms in Korean patients with schizophrenia
      who showed stable symptoms. METHODS: In this 8-week, open-label, prospective, non
      randomized, multicenter study, 34 patients with schizophrenia who showed a stable
      response to previous medications, maintained a stable dose, and who had
      depressive symptoms, were recruited. Ziprasidone was the only antipsychotic agent
      allowed for 8 weeks after a 2-7-week washout period. RESULTS: Steady decreases
      were observed on the Montgomery-Asberg Depression Rating Scale, the Calgary
      Depression Scale for Schizophrenia, the Positive and Negative Syndrome Scale, and
      the Clinical Global Impression-Severity Scale scores. The Montgomery-Asberg
      Depression Rating Scale score was 20.26 +/- 4.77 at baseline and 12.21 +/- 7.94
      at the end-point (P < 0.01). The Calgary Depression Scale for Schizophrenia score
      was 9.76 +/- 4.11 at baseline and 5.00 +/- 3.94 at the end-point (P < 0.01). The
      Positive and Negative Syndrome Scale total score was 75.24 +/- 22.63 at baseline
      and 66.53 +/- 24.28 at the end-point (P < 0.01). The Clinical Global Impression
      Severity Scale score was 3.44 +/- 0.66 at baseline and 3.15 +/- 0.86 at the end
      point (P < 0.05). No significant differences were observed for total scores on
      the Simpson and Angus Rating Scale, the Barnes Akathisia Rating Scale, or the
      Abnormal Involuntary Movement Scale between the baseline and end-point.
      CONCLUSIONS: Ziprasidone was effective for improving depressive symptom scores
      and was well tolerated. Switching to ziprasidone is a good strategy in patients
      with schizophrenia who are experiencing depressive symptoms.

PMID- 24902869
TI  - Effect of tibial plateau angle on cranial cruciate ligament strain: an ex vivo
      study in the dog.
AB  - OBJECTIVE: To evaluate the relationship between tibial plateau angle (TPA) and
      strain in the intact cranial cruciate ligament (CCL) during axial loading. STUDY
      DESIGN: Ex vivo mechanical testing study. SAMPLE POPULATION: Cadaveric canine
      stifles (n = 6). METHODS: A bicentric and uni-radial Slocum saw blade was used to
      perform the osteotomy on each stifle and a custom designed plate was secured to
      the leg. Each stifle was loaded and CCL strain and axial displacement were
      recorded. TPA was adjusted to -20 degrees , -10 degrees , 0 degrees , +10 degrees
      , +20 degrees  of normal. Change in the strain was assessed during the axial
      loading period. RESULTS: For all specimens, linear displacement of the femur and
      CCL strain increased with increasing axial load. Mean change in strain was 4.41,
      5.26, 6.02, 6.3, and 7.39 at -20 degrees , -10 degrees , 0 degrees , 10 degrees ,
      and 20 degrees , respectively. The R-squared for the linear regression equation
      was 0.91, suggesting a strong relationship between change in TPA and CCL strain.
      CONCLUSIONS: The mechanical testing model used found CCL strain increased with
      increasing axial load regardless of the TPA. Decreasing TPA decreased strain in
      the intact CCL.

PMID- 24902870
TI  - Probability versus causal inference in observational studies.

PMID- 24902871
TI  - Relationship between pulse pressure variation and echocardiographic indices of
      left ventricular filling pressure in critically ill patients.
AB  - BACKGROUND: Pulse pressure variation (PPV) is a dynamic index of fluid
      responsiveness. This parameter helps clinicians in improving haemodynamic status
      while avoiding potential fluid overload. Echocardiographic indices, such as E/E'
      ratio and left atrial (LA) strain by speckle tracking echocardiography (STE), are
      used to estimate left ventricular (LV) filling pressures. This study aimed at
      exploring the relationship between PPV and echocardiographic indices of LV
      filling pressures in critically ill patients. METHODS: Twenty-two patients (mean
      age of 50.9 +/- 21.6, male/female = 15/7) admitted to intensive care unit, and
      requiring mechanical ventilation and invasive arterial pressure monitoring, were
      studied. In all patients, two independent operators assessed simultaneously PPV,
      using a pulse contour method, mean E/E' ratio and peak atrial longitudinal strain
      (PALS) by means of STE. PALS values were obtained by averaging LA segments
      measured in the 4-chamber and 2-chamber views (global PALS). RESULTS: A
      significant negative correlation was found between mean E/E' ratio and PPV (R(2)
      = -0.76; P<0.001). A positive correlation between global PALS and PPV was found
      (R(2) = 0.80, P<0.001). Mean global PALS of 26.2% demonstrated excellent accuracy
      (Area Under Roc Curve = 0.86, P<0.001), and good sensitivity (92%) and
      specificity (86%) in predicting a PPV >15%. CONCLUSION: In a group of
      mechanically ventilated patients PPV, derived from pulse contour analysis, and
      echocardiographic preload parameters were well correlated. Global PALS by STE
      provided better estimation of PPV than mean E/E' ratio. PALS seems a potential
      alternative to PPV in assessing fluid responsiveness in critically ill patients.

PMID- 24902872
TI  - Antipsychotics use in children and adolescents: An on-going challenge in clinical
      practice.
AB  - Antipsychotic medications (APs) are a well-established pharmacological treatment
      in adults with serious mental health problems. However, many adult mental health
      disorders have their origins and onset in childhood or adolescence. The
      understanding that neuropsychiatric conditions of childhood are in part
      biologically determined, led to an increase in the number of clinical trials
      supporting evidence on the efficacy of antipsychotic agents as first-line
      treatment for childhood psychotic disorders and therapeutic augmentation of
      nonpsychotic conditions. In recent years the use of antipsychotics in children
      and adolescents for neurodevelopmental, behavioural and psychiatric disorders has
      significantly increased while the age of prescription has decreased. These trends
      have not been matched by advances in the understanding of APs' safety profile in
      this group of patients. It is therefore crucial that current and future practice
      is informed by up-to-date synthesis of the evidence and clinical guidelines about
      the use and monitoring of these treatments in paediatric populations, since the
      effectiveness of early therapeutic interventions in children can affect
      positively the long-term outcome. 

PMID- 24902873
TI  - Changes in hospital and out-patient events and costs following implant naltrexone
      treatment for problematic alcohol use.
AB  - The harmful use of alcohol places a considerable burden on the community, both
      socially and financially. The aim of this study was to determine if the use of
      implant naltrexone is associated with a reduction in health care events and costs
      in patients treated for problematic alcohol use. Ninety four patients (60.6%
      male) treated between 2002 and 2007 were matched against state hospital,
      emergency department (ED), mental health out-patients and mortality data sets for
      6 months prior to and 6 months post treatment. The number of patients, events,
      and costs associated with each health event were compared before and after
      treatment. Overall health care events and costs were reduced from $509033 prior
      to treatment to $270001 following treatment. Costs associated with hospital
      admission showed the most significant reduction, falling from $424605 (82
      admissions/36 patients) before treatment to $203462 (43 admission/24 patients)
      after. While costs associated with ED attendances also fell ($74885 to $54712),
      costs associated with mental health out-patient attendances increased ($9543 to
      $11827). The use of implant naltrexone was associated with a reduction health
      events and costs in patients with problematic alcohol use in the first 6 months
      following treatment. 

PMID- 24902874
TI  - Possible recurrence of symptoms after discontinuation of omalizumab in anti-IgE
      assisted desensitization to egg.

PMID- 24902875
TI  - EDENetworks: a user-friendly software to build and analyse networks in
      biogeography, ecology and population genetics.
AB  - The recent application of graph-based network theory analysis to biogeography,
      community ecology and population genetics has created a need for user-friendly
      software, which would allow a wider accessibility to and adaptation of these
      methods. EDENetworks aims to fill this void by providing an easy-to-use interface
      for the whole analysis pipeline of ecological and evolutionary networks starting
      from matrices of species distributions, genotypes, bacterial OTUs or populations
      characterized genetically. The user can choose between several different
      ecological distance metrics, such as Bray-Curtis or Sorensen distance, or
      population genetic metrics such as FST or Goldstein distances, to turn the raw
      data into a distance/dissimilarity matrix. This matrix is then transformed into a
      network by manual or automatic thresholding based on percolation theory or by
      building the minimum spanning tree. The networks can be visualized along with
      auxiliary data and analysed with various metrics such as degree, clustering
      coefficient, assortativity and betweenness centrality. The statistical
      significance of the results can be estimated either by resampling the original
      biological data or by null models based on permutations of the data. 

PMID- 24902877
TI  - Further investigation of the psychometric properties of the Insulin Treatment
      Appraisal Scale among insulin-using and non-insulin-using adults with type 2
      diabetes: results from Diabetes MILES-Australia.
AB  - BACKGROUND: Negative attitudes towards insulin are commonly reported by people
      with type 2 diabetes mellitus (T2DM) and can act as a barrier to timely insulin
      initiation. The Insulin Treatment Appraisal Scale (ITAS) is a widely used 20-item
      measure of attitudes towards insulin. While designed for completion by both
      insulin using and non-insulin using adults with T2DM, its psychometric properties
      have not been investigated separately for these groups. Furthermore, the total
      score is routinely reported in preference to the published two-factor structure
      (negative/positive appraisals). Further psychometric validation of the ITAS is
      required to examine its properties. METHODS: The ITAS was completed by a subgroup
      of 748 Diabetes MILES-Australia study participants with T2DM, who were either
      insulin using (n = 249; 45% women; mean age = 58 +/- 9 years; mean diabetes
      duration = 13, SD = 8 years) or non-insulin using (n = 499; 47% women; mean age
      57 +/- 9 years; mean diabetes duration 7 +/- 6 years). We replicated the
      psychometric analyses reported in the ITAS development paper. In addition, we
      explored factor structure and investigated internal consistency separately for
      the insulin using and non-insulin using samples. RESULTS: Factor analyses
      supported a two-factor structure with good internal consistency (negative
      subscale alpha = .90; positive subscale alpha = .69). Scale performance differed
      slightly in the insulin using and non-insulin using samples, with some items
      loading inconsistently between groups. A one-factor solution was not supported in
      either sample, with the positive items and some negative items failing to load
      adequately. Consistent with prior research, negative appraisals were
      significantly more common among non-insulin using participants compared to those
      using insulin (d = 1.04), while the positive subscale score did not discriminate
      between groups. CONCLUSIONS: The data supported a two factor structure and the
      positive subscale did not discriminate between insulin using and non-insulin
      using participants. As such, we recommend use of the negative subscale score in
      preference to the ITAS total score, and suggest close attention is paid to the
      relevance of the positive items in the given population.

PMID- 24902876
TI  - The effects of chronic binge alcohol on the genital microenvironment of simian
      immunodeficiency virus-infected female rhesus macaques.
AB  - Alcohol abuse is a widespread problem among those at risk for and living with HIV
      and can impact transmission and disease progression. In this study we sought to
      use the simian immunodeficiency virus (SIV)-macaque model to evaluate the
      immunological and virological changes in the genital microenvironment of females
      exposed to chronic alcohol. Female rhesus macaques were treated with alcohol
      (n=6) or isocaloric sucrose (n=6) for 3 months and then inoculated with
      SIVmac251. To assess the effects of chronic alcohol on SIV disease and the
      genital microenvironment, we quantified plasma and genital SIV levels, measured
      inflammatory cells in genital fluids, and characterized microbial flora by gram
      stains over 10 weeks post-SIV infection. Following 3 months of alcohol/sucrose
      treatment, significant differences were observed in the vaginal microenvironment
      of alcohol-treated animals as compared to controls. Microbial flora of alcohol
      treated animals had decreased levels of lactobacillus morphotypes and increased
      levels of gram-positive cocci relative to sucrose controls. Alcohol-treated
      animals were also more likely to have white blood cells in vaginal fluids prior
      to SIV inoculation, which persisted through viral set point. Similar levels of
      cell-free SIV were observed in plasma and vaginal fluids of both groups, but
      alcohol-treated animals had a higher incidence and levels of cell-associated SIV
      shed in vaginal secretions. Chronic alcohol treatment negatively impacts the
      genital microenvironment prior to and over the course of SIV infection and may
      increase the risk of genital virus shedding and transmission.

PMID- 24902878
TI  - Factors influencing registered nurses perception of their overall job
      satisfaction: a qualitative study.
AB  - AIM: The purpose of this qualitative descriptive study was to explore factors
      related to critical care and medical-surgical nurses' job satisfaction as well as
      dissatisfaction in Iran. BACKGROUND: Job satisfaction is an important factor in
      healthcare settings. Strong empirical evidence supports a causal relationship
      between job satisfaction, patient safety and quality of care. METHOD: A
      convenient sample of 85 nurses from surgical, medical and critical care wards of
      a large hospital was recruited. Ten focus group discussions using a semi
      structured interview guide were conducted. Interviews were audio-recorded,
      transcribed verbatim and analysed using a thematic approach. FINDINGS: The study
      identified three main themes that influenced nurses' job satisfaction and
      dissatisfaction: (1) spiritual feeling, (2) work environment factors, and (3)
      motivation. Helping and involvement in patient care contributed to the spiritual
      feeling reported to influence nurses' job satisfaction. For work environment
      factors, team cohesion, benefit and rewards, working conditions, lack of medical
      resources, unclear nurses' responsibilities, patient and doctor perceptions, poor
      leadership skills and discrimination at work played an important role in nurses'
      job dissatisfaction. For motivation factors, task requirement, professional
      development and lack of clinical autonomy contributed to nurses' job
      satisfaction. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse
      managers should ensure a flexible practice environment with adequate staffing and
      resources with opportunities for nurses to participate in hospital's policies and
      governance. Policy makers should consider nurses' professional development needs,
      and implement initiatives to improve nurses' rewards and other benefits as they
      influence job satisfaction.

PMID- 24902879
TI  - Epidermal growth factor receptor-GEP100-Arf6 axis affects the prognosis of lung
      adenocarcinoma.
AB  - The overexpression of Arf6 and GEP100 is responsible for the invasive activity
      that is crucial for the activation of the epidermal growth factor receptor (EGFR)
      signaling pathways in human cancer. However, whether or not the expression of the
      EGFR-GEP100-Arf6 axis can be used as a biomarker for the prognosis of lung cancer
      has yet to be fully determined. Tumor specimens were collected from 182 patients
      who underwent a complete resection for lung adenocarcinoma. We analyzed phospho
      EGFR (p-EGFR), GEP100, and Arf6 expression levels in the primary tumor by
      immunohistochemical analysis. The expression of p-EGFR, GEP100, and Arf6 was
      observed in 65 (35.7%), 95 (52.2%), and 20 (11.0%) patients, respectively.
      Significant associations between p-EGFR and GEP100 expression and vessel invasion
      were identified. The expression of these individual molecules was not associated
      with any statistically significant differences in survival. However, triple
      positive expression of p-EGFR, GEP100, and Arf6 was significantly associated with
      an increased risk of death based on the multivariate analysis. The EGFR-GEP100
      Arf6 axis affected the prognosis of patients with primary lung adenocarcinoma.
      The combination of p-EGFR, GEP100, and Arf6 staining can predict the prognosis of
      patients after surgery.

PMID- 24902880
TI  - Competing risks model in screening for preeclampsia by biophysical and
      biochemical markers at 30-33 weeks' gestation.
AB  - OBJECTIVE: To assess the risk for preeclampsia (PE) by maternal characteristics,
      uterine artery pulsatility index (Ut-PI), mean arterial pressure (MAP), serum
      placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at
      30-33 weeks' gestation. METHODS: This was a screening study in singleton
      pregnancies including 2,140 that developed PE and 83,615 that were unaffected by
      PE. We developed a survival time model for the time of delivery for PE by
      combining maternal characteristics and history with Ut-PI, MAP, PlGF and sFlt-1
      multiple of the median (MoM) values (combined test). Data on third-trimester MAP
      and Ut-PI were available in 350 cases of PE, and 13,878 unaffected pregnancies
      and data on PlGF and sFlt-1 were available in 118 cases of PE and 3,734
      unaffected pregnancies. Modelled detection rate of all PE and PE requiring
      delivery within 4 and 6 weeks of the visit was estimated. RESULTS: Screening by
      the combined test would detect 66, 98 and 86% of all PE and PE requiring delivery
      within 4 and 6 weeks of the visit, respectively, at a false positive rate of 5%.
      INTERPRETATION: Screening by biophysical and biochemical testing at 30-33 weeks
      could identify most pregnancies developing PE and requiring delivery within the
      subsequent 4 weeks.

PMID- 24902881
TI  - Identification of the optimum vagal manoeuvre technique for maximising vagal
      tone.
AB  - OBJECTIVES: This study sought to determine the most effective technique for
      Valsalva Manoeuvre (VM) and Human Dive Reflex Manoeuvre (HDR) generation of vagal
      tone. METHODS: We conducted a repeated-measures trial of healthy adult volunteers
      from a university campus, aged 18-56 years, in sinus rhythm. Participants were
      randomised to VM (in supine or Trendelenberg postures) and HDR (supine or sitting
      postures) sequentially. Participants performed three trials of each technique, in
      random order, with a continuous ECG recording. Single-blinded analysis of ECG
      data was conducted. Mean differences between premanoeuvre and postmanoeuvre R-R
      intervals and heart rates were calculated for each posture within and between
      vagal manoeuvres. RESULTS: Seventy-two participants were enrolled. The difference
      between VM (supine) and VM (Trendelenberg) was not significant at 0.008 s (-0.023
      to 0.038). The difference in mean R-R intervals for HDR (supine) was greater than
      HDR (sitting) 0.062 (0.031 to 0.093), although this significance was not
      reflected in a heart-rate change of -0.87 (-3.00 to 1.26). VM supine generated
      greatest overall mean R-R interval difference, while HDR (sitting) provided the
      smallest change in R-R interval. The VM (supine) provided a significant maximum
      effectiveness over the HDR (supine) of 0.102 s (0.071 to 0.132). CONCLUSIONS:
      This study demonstrates that VM (supine) generates the greatest vagal tone
      producing the largest transient heart rate decrease in healthy volunteers. No
      advantage was identified in Trendelenberg posturing for the VM in this study.
      These results may assist in the standardisation of vagal manoeuvre technique for
      the range of therapeutic and diagnostic applications.

PMID- 24902882
TI  - Paediatric ED reattendance rates: comparing nurse practitioners and other
      clinicians.
AB  - OBJECTIVE: The aim of this project is to establish the unplanned reattendance
      rate for paediatric emergency nurse practitioners (PENPs) working in a designated
      paediatric emergency department (PED) while identifying the case mix of patients
      seen by PENPs compared with their medical counterparts. DESIGN: Quantitative data
      regarding patient characteristics and reattendance were collected during
      retrospective review of case notes across two representative 2-week periods.
      SETTING: The study site is a tertiary urban PED with an annual attendance of 32
      000 patients aged from birth to 15 years. MAIN OUTCOME MEASURES: Reattendance
      rates, patient characteristics, triage scores, presenting complaint and numbers
      of patients discussed with a paediatric emergency medicine consultant were
      evaluated. RESULTS: The results showed that PENPs have a lower reattendance rate
      (1.75%) when compared with senior and junior doctors in training (4.29%, 5.76%);
      however, PENPs treat a different population of children. When the odds of PENP
      reattendance are adjusted for this, the significance of the difference becomes
      less certain. CONCLUSIONS: PENPs work autonomously when seeing children
      presenting with minor trauma and make a positive contribution in achieving the
      reattendance Clinical Quality Indicator.

PMID- 24902883
TI  - Measuring political commitment and opportunities to advance food and nutrition
      security: piloting a rapid assessment tool.
AB  - Lack of political commitment has been identified as a primary reason for the low
      priority that food and nutrition interventions receive from national governments
      relative to the high disease burden caused by malnutrition. Researchers have
      identified a number of factors that contribute to food and nutrition's 'low
      priority cycle' on national policy agendas, but few tools exist to rapidly
      measure political commitment and identify opportunities to advance food and
      nutrition on the policy agenda. This article presents a theory-based rapid
      assessment approach to gauging countries' level of political commitment to food
      and nutrition security and identifying opportunities to advance food and
      nutrition on the policy agenda. The rapid assessment tool was piloted among food
      and nutrition policymakers and planners in 10 low- and middle-income countries in
      April to June 2013. Food and nutrition commitment and policy opportunity scores
      were calculated for each country and strategies to advance food and nutrition on
      policy agendas were designed for each country. The article finds that, in a
      majority of countries, political leaders had verbally and symbolically committed
      to addressing food and nutrition, but adequate financial resources were not
      allocated to implement specific programmes. In addition, whereas the low cohesion
      of the policy community has been viewed a major underlying cause of the low
      priority status of food and nutrition, the analysis finds that policy community
      cohesion and having a well thought-out policy alternative were present in most
      countries. This tool may be useful to policymakers and planners providing
      information that can be used to benchmark and/or evaluate advocacy efforts to
      advance reforms in the food and nutrition sector; furthermore, the results can
      help identify specific strategies that can be employed to move the food and
      nutrition agenda forward. This tool complements others that have been recently
      developed to measure national commitment to advancing food and nutrition
      security. 

PMID- 24902884
TI  - Time and deprivation trends in incidence of primary liver cancer subtypes in
      England.
AB  - RATIONALE, AIMS AND OBJECTIVES: Primary liver cancer consists of distinct
      subtypes with differing aetiology so it is valuable to study the incidence of
      these subtypes separately. This study aims to investigate time and socio-economic
      deprivation trends in the incidence of primary liver cancer subtypes in England,
      identifying the burden in the population. METHODS: Data were extracted from the
      population-based National Cancer Data Repository (NCDR) for patients diagnosed
      with primary liver cancer between 1990 and 2009. Subtypes were defined by the
      10th edition of the International Classification of Diseases (ICD-10) codes:
      liver cell carcinoma (C22.0), intrahepatic bile duct carcinoma (C22.1), other
      (C22.2-C22.4, C22.7) and unspecified (C22.9). A sensitivity analysis was carried
      out on the main histological subtypes of liver cell carcinoma and intrahepatic
      bile duct using the 2nd edition of the International Classification of Diseases
      for Oncology (ICD-O-2). Male and female age-standardized incidence rates per 100
      000 World standard population were calculated for each year and for the period
      1999-2009 by socio-economic deprivation quintile. RESULTS: A total of 40 945
      patients were diagnosed with primary liver cancer between 1990 and 2009. Liver
      cell carcinoma incidence increased in men from 0.63 in 1990 to 2.48 per 100 000
      in 2009. While incidence was low in women, rates increased from 0.18 to 0.59,
      respectively. Intrahepatic bile duct carcinoma incidence increased between 1990
      and 2009 from 0.40 to 1.25 per 100 000 in men, and from 0.28 to 1.08 in women.
      Incidence of the other liver cancer subtype remained low throughout the study
      period at less than 0.3 per 100 000 in each year in both men and women. The
      highest rate of liver cell carcinoma and intrahepatic bile duct carcinoma was
      generally in men and women resident in the most deprived areas between 1999 and
      2009. The largest difference by deprivation quintile was observed for liver cell
      carcinoma in men, where the incidence was more than double in the most deprived
      quintile with an average rate of 3.56 per 100 000 compared to the least deprived
      quintile at 1.43. CONCLUSIONS: Liver cell carcinoma and intrahepatic bile duct
      carcinoma incidence increased between 1990 and 2009 in both sexes. This pattern
      was largely driven by patients living in the most deprived areas. Differences
      observed may be due to the variation in the prevalence of known risk factors such
      as chronic hepatitis B and C viral infections and excessive alcohol consumption.

PMID- 24902885
TI  - Plastidic aspartate aminotransferases and the biosynthesis of essential amino
      acids in plants.
AB  - In the chloroplasts and in non-green plastids of plants, aspartate is the
      precursor for the biosynthesis of different amino acids and derived metabolites
      that play distinct and important roles in plant growth, reproduction, development
      or defence. Aspartate biosynthesis is mediated by the enzyme aspartate
      aminotransferase (EC 2.6.1.1), which catalyses the reversible transamination
      between glutamate and oxaloacetate to generate aspartate and 2-oxoglutarate.
      Plastids contain two aspartate aminotransferases: a eukaryotic-type and a
      prokaryotic-type bifunctional enzyme displaying aspartate and prephenate
      aminotransferase activities. A general overview of the biochemistry, regulation,
      functional significance, and phylogenetic origin of both enzymes is presented.
      The roles of these plastidic aminotransferases in the biosynthesis of essential
      amino acids are discussed. 

PMID- 24902886
TI  - Al13@Pt42 core-shell cluster for oxygen reduction reaction.
AB  - To increase Pt utilization for oxygen reduction reaction (ORR) in fuel cells,
      reducing particle sizes of Pt is a valid way. However, poisoning or surface
      oxidation limits the smallest size of Pt particles at 2.6 nm with a low utility
      of 20%. Here, using density functional theory calculations, we develop a core
      shell Al13@Pt42 cluster as a catalyst for ORR. Benefit from alloying with Al in
      this cluster, the covalent Pt-Al bonding effectively activates the Pt atoms at
      the edge sites, enabling its high utility up to 70%. Valuably, the adsorption
      energy of O is located at the optimal range with 0.0-0.4 eV weaker than Pt(111),
      while OH-poisoning does not observed. Moreover, ORR comes from O2 dissociation
      mechanism where the rate-limiting step is located at OH formation from O and H
      with a barrier of 0.59 eV, comparable with 0.50 eV of OH formation from O and H2O
      on Pt(111). 

PMID- 24902887
TI  - Similar psychopathological profiles in female and male Cushing's disease patients
      after treatment but differences in the pathogenesis of symptoms.
AB  - BACKGROUND: Female Cushing's disease (CD) patients with active disease present
      more frequently with depression compared to their male co-sufferers. This study
      investigated whether the gender difference prevails after remission and whether
      gender-specific factors contributing to mental health exist. METHODS: 72
      biochemically cured CD patients (11 male, mean age 45.9 +/- 13.7 years) who
      underwent transsphenoidal tumour removal filled out the Symptom Checklist-90
      Revised inventory on average 42.1 +/- 32.9 months after surgery. Multiple
      regression analyses included the following independent factors: (i) age, (ii)
      presence of comorbidities, (iii) presence of hypocortisolism, (iv) presence of
      hypopituitarism, (v) disease duration until diagnosis, (vi) time elapsed since
      surgery, and (vii) postoperative radiotherapy to predict postoperative
      psychopathology. RESULTS: Regarding the Global Severity Index, 23.0% of the
      female and 27.3% of the male CD patients presented with abnormal scores. In all
      nine dimensions, psychopathological abnormalities were present in both female and
      male patients with the same frequency and intensity (each p > 0.05). Prolonged
      time to diagnosis was a strong predictive factor for worse psychopathological
      status only in male patients. Among female patients, only the presence of
      comorbidities and to some extent pituitary deficiencies were related to
      psychopathological status. CONCLUSIONS: During the remission phase of CD, female
      and male patients present with similar psychopathological profiles. In males,
      long-term biochemical effects of previous hypercortisolism seem to be salient for
      psychopathology. In contrast, in females, the presence of comorbidities/stressors
      they have to cope with is the predictive factor for psychopathology. The results
      underline gender differences in CD and the need to separate them on various
      issues.

PMID- 24902888
TI  - Effect of mild pressure applied by the ultrasound transducer on fetal cephalic
      measurements at 20-24 weeks' gestation.
AB  - INTRODUCTION: The aim of this study was to assess the effect of mild pressure
      applied on the abdominal wall by the ultrasound transducer on fetal cephalic
      indices. MATERIAL AND METHODS: We examined by ultrasound 60 fetuses of healthy
      women, at 20-24 weeks of pregnancy, during routine prenatal evaluation. For every
      fetus biparietal diameter and head circumference were measured, with and without
      applying mild pressure by the ultrasound transducer. The weight and gestational
      age (GA) were calculated. RESULTS: The pressure applied by the transducer had a
      significant effect on the cephalic indices and on the weight and GA evaluations
      (p < 0.001). Fetal positioning significantly affected the impact that applied
      pressure had on head circumference and on the weight evaluation derived from it
      (p < 0.05). DISCUSSION: Applied pressure by an abdominal ultrasound probe affects
      cephalic indices and the derived weight and GA estimations. This may lead to
      incorrect diagnoses or hide pathological findings. The effect of applied pressure
      depends on fetal positioning. The examiner must be aware of this effect when
      evaluating the results of the measurements.

PMID- 24902889
TI  - Oral health determinants and caries outcome among non-privileged children.
AB  - The study aimed at identifying oral health determinants that are present in early
      childhood, are amenable to change and for which there is evidence of their
      modulation of the rate of caries progression in a sample of non-privileged
      children. The null hypothesis was that determinants associated with the child's
      institutional environment as evidenced by nursery policies significantly
      influenced the child's oral health. The sample was formed by 2,511 Brazilian 1-5
      year-olds. Caries severity and activity were recorded. Parents were interviewed
      and nurseries answered a questionnaire. According to the case status d1efs, the
      final multilevel model (generalized linear mixed model) identified significant
      associations with determinants such as bottle-feeding the child during the night
      on demand, not assisting the child in toothbrushing, ensuring visit to the
      dentist in case of troubles with teeth only (p < 0.0001) and intake of sugary
      products 2-4 times daily at nursery (p = 0.026). The likelihood of caries
      outcomes was associated with determinants related to nursery policies, not
      promoting preventive oral health care for children of mothers with 4 years of
      education (OR = 2.14; p < 0.0015) and <4 years of education (OR = 2.6; p =
      0.0010), as well as consumption of sugary products 2-4 times daily for children
      of mothers with 4 years of education (OR = 3.35; p = 0.0010) and <4 years of
      education (OR = 4.07; p = 0.0063). In conclusion, determinants related to
      parental negative practices and to nursery policies significantly influenced
      children's oral health. Of particular interest was the identification of
      determinants considered amenable to change in connection with nursery policies
      towards oral health.

PMID- 24902890
TI  - Low-allergenic hydrolyzed egg induces oral tolerance in mice.
AB  - BACKGROUND: Egg allergy is one of the most common food allergies in children. The
      standard therapy for egg allergy is strict avoidance. Yet, there is considerable
      clinical and scientific interest in primary or secondary prevention. A major
      drawback of oral tolerance (OT) induction protocols, however, is the possibility
      of severe side effects; thus, we have formulated a hypoallergenic egg product and
      demonstrate its in vivo capacity to modulate the immune system in the current
      study. METHODS: Hydrolyzed egg (HE) was produced using a combination of moderate
      heat treatment and enzymatic hydrolysis. The capacity of HE to induce OT was
      tested in experimental models and compared to whole egg (WE). Delayed-type
      hypersensitivity (DTH) responses, immune markers and potential early markers of
      OT were analyzed. RESULTS: Allergic responses, assessed by both DTH responses
      upon OVA challenge and serum OVA-specific IgE and IgG1, were decreased after
      treatment with HE and WE compared to the control group. Additionally, feeding WE
      and HE significantly decreased Th2 cytokine induction and cell proliferation,
      induced the activation of effector CD4+ T cells and increased numbers and
      percentages of ICOS+CD4+CD25+Foxp3+ cells. Furthermore, DO11.10 mouse experiments
      showed that HE contains other peptides than the OVA323-339 peptide that are able
      to induce tolerance to OVA. CONCLUSIONS: Altogether, results showed that HE
      induces OT in mice in a dose-dependent manner. Due to its low allergenicity
      compared to WE, it may represent a safer alternative for OT induction in at-risk
      subjects or oral immunotherapy in allergic patients.

PMID- 24902891
TI  - Motor imagery and electrical stimulation reproduce corticospinal excitability at
      levels similar to voluntary muscle contraction.
AB  - BACKGROUND: The combination of voluntary effort and functional electrical
      stimulation (ES) appears to have a greater potential to induce plasticity in the
      motor cortex than either electrical stimulation or voluntary training alone.
      However, it is not clear whether the motor commands from the central nervous
      system, the afferent input from peripheral organs, or both, are indispensable to
      induce the facilitative effects on cortical excitability. To clarify whether
      voluntary motor commands enhance corticospinal tract (CoST) excitability during
      neuromuscular ES, without producing voluntary muscular contraction (VMC), we
      examined the effect of a combination of motor imagery (MI) and electrical
      muscular stimulation on CoST excitability using transcranial magnetic stimulation
      (TMS). METHODS: Eight neurologically healthy male subjects participated in this
      study. Five conditions (resting, MI, ES, ES + MI [ESMI], and VMC) were
      established. In the ES condition, a 50-Hz stimulus was applied for 3 to 5 s to
      the first dorsal interosseous (FDI) while subjects were relaxed. In the MI
      condition, subjects were instructed to imagine abducting their index finger. In
      the ESMI condition, ES was applied approximately 1 s after the subject had begun
      to imagine index finger abduction. In the VMC condition, subjects modulated the
      force of index finger abduction to match a target level, which was set at the
      level produced during the ES condition. TMS was applied on the hotspot for FDI,
      and the amplitude and latency of motor evoked potentials (MEPs) were measured
      under each condition. RESULTS: MEP amplitudes during VMC and ESMI were
      significantly larger than those during other conditions; there was no significant
      difference in MEP amplitude between these 2 conditions. The latency of MEPs
      evoked during MI and VMC were significantly shorter than were those evoked during
      rest and ES. CONCLUSIONS: MEP acutely reinforced in ESMI may indicate that
      voluntary motor drive markedly contributes to enhance CoST excitability, without
      actual muscular contraction.

PMID- 24902893
TI  - Adsorption dominant catalytic activity of a carbon dots stabilized gold
      nanoparticles system.
AB  - Carbon dots (CDs) with abundant functional groups (-OH, -COOH, C=O) on their
      surface were specially designed to enhance the adsorption capacity and the
      catalytic activity of gold nanoparticles (AuNPs). The CDs stabilized gold
      nanoparticles (AuNPs-CDs) were greenly synthesized by a one-step reduction of
      HAuCl4 with CDs which were used as both the reductant and the stabilizer under
      visible light irradiation. The resulting AuNPs-CDs exhibit a high catalytic
      activity towards the reduction of 4-nitrophenol, with a good linear correlation
      of ln(C(i)/C0) versus time and a kinetic rate constant about 0.68 min(-1).
      Further detailed adsorption kinetics data indicated that the present adsorption
      system follows a predominantly second-order rate model, and the CDs capped on the
      surface of the AuNPs also enhanced the adsorption capacity and the catalytic
      activity of the AuNPs.

PMID- 24902892
TI  - AtMYB93 is a novel negative regulator of lateral root development in Arabidopsis.
AB  - Plant root system plasticity is critical for survival in changing environmental
      conditions. One important aspect of root architecture is lateral root
      development, a complex process regulated by hormone, environmental and protein
      signalling pathways. Here we show, using molecular genetic approaches, that the
      MYB transcription factor AtMYB93 is a novel negative regulator of lateral root
      development in Arabidopsis. We identify AtMYB93 as an interaction partner of the
      lateral-root-promoting ARABIDILLO proteins. Atmyb93 mutants have faster lateral
      root developmental progression and enhanced lateral root densities, while AtMYB93
      overexpressing lines display the opposite phenotype. AtMYB93 is expressed
      strongly, specifically and transiently in the endodermal cells overlying early
      lateral root primordia and is additionally induced by auxin in the basal meristem
      of the primary root. Furthermore, Atmyb93 mutant lateral root development is
      insensitive to auxin, indicating that AtMYB93 is required for normal auxin
      responses during lateral root development. We propose that AtMYB93 is part of a
      novel auxin-induced negative feedback loop stimulated in a select few endodermal
      cells early during lateral root development, ensuring that lateral roots only
      develop when absolutely required. Putative AtMYB93 homologues are detected
      throughout flowering plants and represent promising targets for manipulating root
      systems in diverse crop species. 

PMID- 24902895
TI  - Bioinspired micro-/nanostructure fibers with a water collecting property.
AB  - We review the recent research on structure-induced water collecting properties of
      spider silk and bioinspired fibers. Since the capture silks of cribellate spiders
      have a unique wet-rebuilt structure with spindle-knots and joints for directional
      water collection, we were inspired to fabricate a series of artificial gradient
      micro-/nanostructure fibers. These fibers display excellent functions, such as
      driving tiny water drops in certain directions, water capturing, multi-gradient
      cooperation effect, and wet-response to environmental humidity. This review is
      helpful to the design of novel smart functional materials that can be extended to
      develop devices or systems for water collection, sensors, fluid-control, filters
      and others. 

PMID- 24902896
TI  - Anaerobic/aerobic conditions and biostimulation for enhanced chlorophenols
      degradation in biocathode microbial fuel cells.
AB  - Anaerobic/aerobic conditions affected bacterial community composition and the
      subsequent chlorophenols (CPs) degradation in biocathode microbial fuel cells
      (MFCs). Bacterial communities acclimated with either 4-chlorophenol (4-CP) or 2,4
      dichlorophenol (2,4-DCP) under anaerobiosis can degrade the respective substrates
      more efficiently than the facultative aerobic bacterial communities. The
      anaerobic bacterial communities well developed with 2,4-DCP were then adapted to
      2,4,6-trichlorophenol (2,4,6-TCP) and successfully stimulated for enhanced 2,4,6
      TCP degradation and power generation. A 2,4,6-TCP degradation rate of 0.10
      mol/m(3)/d and a maximum power density of 2.6 W/m(3) (11.7 A/m(3)) were achieved,
      138 and 13 % improvements, respectively compared to the controls with no
      stimulation. Bacterial communities developed with the specific CPs under
      anaerobic/aerobic conditions as well as the stimulated biofilm shared some
      dominant genera and also exhibited great differences. These results provide the
      most convincing evidence to date that anaerobic/aerobic conditions affected CPs
      degradation with power generation from the biocathode systems, and using
      deliberate substrates can stimulate the microbial consortia and be potentially
      feasible for the selection of an appropriate microbial community for the target
      substrate (e.g. 2,4,6-TCP) degradation in the biocathode MFCs.

PMID- 24902894
TI  - Short leukocyte telomere length predicts incidence and progression of carotid
      atherosclerosis in American Indians: the Strong Heart Family Study.
AB  - Short leukocyte telomere length (LTL) has been associated with atherosclerosis in
      cross-sectional studies, but the prospective relationship between telomere
      shortening and risk of developing carotid atherosclerosis has not been well
      established. This study examines whether LTL at baseline predicts incidence and
      progression of carotid atherosclerosis in American Indians in the Strong Heart
      Study. The analysis included 2,819 participants who were free of overt
      cardiovascular disease at baseline (2001-2003) and were followed through the end
      of 2006-2009 (average 5.5-yr follow-up). Discrete atherosclerotic plaque was
      defined as focal protrusion with an arterial wall thickness >=50% the surrounding
      wall. Carotid progression was defined as having a higher plaque score at the end
      of study follow-up compared to baseline. Associations of LTL with incidence and
      progression of carotid plaque were examined using Cox proportional hazard
      regression, adjusting for standard coronary risk factors. Compared to
      participants in the highest LTL tertile, those in the lowest tertile had
      significantly elevated risk for both incident plaque (HR, 1.49; 95% CI, 1.09
      2.03) and plaque progression (HR, 1.61; 95% CI, 1.26-2.07). Our results provide
      initial evidence for a potential prognostic utility of LTL in risk prediction for
      atherosclerosis. 

PMID- 24902897
TI  - A highly sensitive nanoscale pH-sensor using Au nanoparticles linked by a
      multifunctional Raman-active reporter molecule.
AB  - Chemical sensing on the nanoscale has been breaking new ground since the
      discovery of surface enhanced Raman scattering (SERS). For nanoparticles,
      controlled particle aggregation is necessary to achieve the largest SERS
      enhancements. Therefore, aggregating agents such as salts or linker molecules are
      used in conjunction with chemically sensitive reporters in order to develop
      robust environmentally sensitive SERS probes. While salt-induced colloidal
      nanosphere aggregates have produced robust SERS signals, their variability in
      aggregate size contributes significantly to poor SERS signal reproducibility,
      which can complicate their use in in vitro cellular studies. Such systems often
      also lack reproducibility in spectral measurements between different nanoparticle
      clusters. Preaggregation of colloids via linkers followed by surface
      functionalization with reporter molecules results in the linker occupying
      valuable SERS hotspot volume which could otherwise be utilized by additional
      reporter molecules. Ideally, both functionalities should be obtained from a
      single molecule. Here, we report the use of 3,5-dimercaptobenzoic acid, a single
      multifunctional molecule that creates SERS hotspots via the controlled
      aggregation of nanoparticles, and also reports pH values. We show that 3,5
      dimercaptobenzoic acid bound to Au nanospheres results in an excellent pH
      nanoprobe, producing very robust, and highly reproducible SERS signals that can
      report pH across the entire physiological range with excellent pH resolution. To
      demonstrate the efficacy of our novel pH reporters, these probes were also used
      to image both the particle and pH distribution in the cytoplasm of human induced
      pluripotent stem cells (hiPSCs). 

PMID- 24902898
TI  - Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN
      formation by modulating Kras(G12D)-induced senescence.
AB  - Nuclear protein 1 (Nupr1), a small chromatin protein, has a critical role in
      cancer development, progression and resistance to therapy. Previously, we had
      demonstrated that Nupr1 cooperates with Kras(G12D) to induce pancreas
      intraepithelial neoplasias (PanIN) formation and pancreatic ductal adenocarcinoma
      development in mice. However, the molecular mechanisms by which Nupr1 influences
      Kras-mediated preneoplastic growth remain to be fully characterized. In the
      current study, we report evidence supporting a role for Nupr1 as a gene modifier
      of Kras(G12D)-induced senescence, which must be overcome to promote PanIN
      formation. We found that genetic inactivation of Nupr1 in mice impairs Kras
      induced PanIN, leading to an increase in beta-galactosidase-positive cells and an
      upregulation of surrogate marker genes for senescence. More importantly, both of
      these cellular and molecular changes are recapitulated by the results of
      mechanistic experiments using RNAi-based inactivation of Nupr1 in human
      pancreatic cancer cell models. In addition, the senescent phenotype, which
      results from Nupr1 inactivation, is accompanied by activation of the FoxO3a-Skp2
      p27(Kip1)-pRb-E2F pathway in vivo and in vitro. Thus, combined, these results
      show, for the first time, that Nupr1 aids oncogenic Kras to bypass senescence in
      a manner that cooperatively promotes PanIN formation. Besides its mechanistic
      importance, this new knowledge bears medical relevance as it delineates early
      pathobiological events that may be targeted in the future as a means to interfere
      with the formation of preneoplastic lesions early during pancreatic
      carcinogenesis. 

PMID- 24902899
TI  - RIPK1- and RIPK3-induced cell death mode is determined by target availability.
AB  - Both receptor-interacting protein kinase 1 (RIPK1) and RIPK3 can signal cell
      death following death receptor ligation. To study the requirements for RIPK
      triggered cell death in the absence of death receptor signaling, we engineered
      inducible versions of RIPK1 and RIPK3 that can be activated by dimerization with
      the antibiotic coumermycin. In the absence of TNF or other death ligands,
      expression and dimerization of RIPK1 was sufficient to cause cell death by
      caspase- or RIPK3-dependent mechanisms. Dimerized RIPK3 induced cell death by an
      MLKL-dependent mechanism but, surprisingly, also induced death mediated by FADD,
      caspase 8 and RIPK1. Catalytically active RIPK3 kinase domains were essential for
      MLKL-dependent but not for caspase 8-dependent death. When RIPK1 or RIPK3
      proteins were dimerized, the mode of cell death was determined by the
      availability of downstream molecules such as FADD, caspase 8 and MLKL. These
      observations imply that rather than a 'switch' operating between the two modes of
      cell death, the final mechanism depends on levels of the respective signaling and
      effector proteins. 

PMID- 24902900
TI  - Cerium oxide nanoparticles protect against Abeta-induced mitochondrial
      fragmentation and neuronal cell death.
AB  - Evidence indicates that nitrosative stress and mitochondrial dysfunction
      participate in the pathogenesis of Alzheimer's disease (AD). Amyloid beta (Abeta)
      and peroxynitrite induce mitochondrial fragmentation and neuronal cell death by
      abnormal activation of dynamin-related protein 1 (DRP1), a large GTPase that
      regulates mitochondrial fission. The exact mechanisms of mitochondrial
      fragmentation and DRP1 overactivation in AD remain unknown; however, DRP1 serine
      616 (S616) phosphorylation is likely involved. Although it is clear that
      nitrosative stress caused by peroxynitrite has a role in AD, effective
      antioxidant therapies are lacking. Cerium oxide nanoparticles, or nanoceria,
      switch between their Ce(3+) and Ce(4+) states and are able to scavenge superoxide
      anions, hydrogen peroxide and peroxynitrite. Therefore, nanoceria might protect
      against neurodegeneration. Here we report that nanoceria are internalized by
      neurons and accumulate at the mitochondrial outer membrane and plasma membrane.
      Furthermore, nanoceria reduce levels of reactive nitrogen species and protein
      tyrosine nitration in neurons exposed to peroxynitrite. Importantly, nanoceria
      reduce endogenous peroxynitrite and Abeta-induced mitochondrial fragmentation,
      DRP1 S616 hyperphosphorylation and neuronal cell death. 

PMID- 24902901
TI  - The PI3K regulatory subunits p55alpha and p50alpha regulate cell death in vivo.
AB  - The phosphatidylinositol 3-kinase (PI3K) regulatory subunits p55alpha and
      p50alpha are coordinately transcriptionally upregulated by signal transducer and
      activator of transcription 3 (Stat3) at the onset of mammary gland involution, a
      process that requires Stat3. Deletion of both p55alpha and p50alpha subunits in
      vivo abrogated mammary epithelial cell death during involution. This was
      associated also with reduced cytosolic levels and activity of the cysteine
      protease cathepsin L, which is implicated in lysosomal-mediated programmed cell
      death (LM-PCD) and is upregulated in involution. Furthermore, involution is
      delayed in cathepsin L-deficient mice suggesting that the p55alpha/p50alpha
      subunits mediate cell death in part by elevating the level of cathepsin L
      resulting in increased cytosolic activity. Surprisingly, we found that
      p55alpha/p50alpha localize to the nucleus where they bind to chromatin and
      regulate transcription of a subset of inflammatory/acute phase genes that are
      also Stat3 targets. Our findings reveal a novel role for these PI3K regulatory
      subunits as regulators of LM-PCD in vivo. 

PMID- 24902902
TI  - Distinct roles of RIP1-RIP3 hetero- and RIP3-RIP3 homo-interaction in mediating
      necroptosis.
AB  - Necroptosis is mediated by a signaling complex called necrosome, containing
      receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like
      (MLKL). It is known that RIP1 and RIP3 form heterodimeric filamentous scaffold in
      necrosomes through their RIP homotypic interaction motif (RHIM) domain-mediated
      oligomerization, but the signaling events based on this scaffold has not been
      fully addressed. By using inducible dimer systems we found that RIP1-RIP1
      interaction is dispensable for necroptosis; RIP1-RIP3 interaction is required for
      necroptosis signaling, but there is no necroptosis if no additional RIP3 protein
      is recruited to the RIP1-RIP3 heterodimer, and the interaction with RIP1 promotes
      the RIP3 to recruit other RIP3; RIP3-RIP3 interaction is required for necroptosis
      and RIP3-RIP3 dimerization is sufficient to induce necroptosis; and RIP3 dimer
      induced necroptosis requires MLKL. We further show that RIP3 oligomer is not more
      potent than RIP3 dimer in triggering necroptosis, suggesting that RIP3 homo
      interaction in the complex, rather than whether RIP3 has formed homo polymer, is
      important for necroptosis. RIP3 dimerization leads to RIP3 intramolecule
      autophosphorylation, which is required for the recruitment of MLKL.
      Interestingly, phosphorylation of one of RIP3 in the dimer is sufficient to
      induce necroptosis. As RIP1-RIP3 heterodimer itself cannot induce necroptosis,
      the RIP1-RIP3 heterodimeric amyloid fibril is unlikely to directly propagate
      necroptosis. We propose that the signaling events after the RIP1-RIP3 amyloid
      complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloid
      scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of
      MLKL by RIP3 to execute necroptosis. 

PMID- 24902905
TI  - The future training of combat medical technicians-where next?

PMID- 24902903
TI  - Lhx2 regulates bone remodeling in mice by modulating RANKL signaling in
      osteoclasts.
AB  - The LIM homeobox 2 (Lhx2) transcription factor Lhx2 has a variety of functions,
      including neural induction, morphogenesis, and hematopoiesis. Here we show the
      involvement of Lhx2 in osteoclast differentiation. Lhx2 was strongly expressed in
      osteoclast precursor cells but its expression was significantly reduced during
      receptor activator of nuclear factor-kappaB ligand (RANKL)-mediated
      osteoclastogenesis. Overexpression of Lhx2 in bone marrow-derived
      monocyte/macrophage lineage cells (BMMs), which are osteoclast precursor cells,
      attenuated RANKL-induced osteoclast differentiation by inhibiting the induction
      of nuclear factor of activated T cells c1 (NFATc1). Interestingly, interaction of
      Lhx2 proteins with c-Fos attenuated the DNA-binding ability of c-Fos and thereby
      inhibited the transactivation of NFATc1. Furthermore, Lhx2 conditional knockout
      mice exhibited an osteoporotic bone phenotype, which was related with increased
      osteoclast formation in vivo. Taken together, our results suggest that Lhx2 acts
      as a negative regulator of osteoclast formation in vitro and in vivo. The anti
      osteoclastogenic effect of Lhx2 may be useful for developing a therapeutic
      strategy for bone disease. 

PMID- 24902906
TI  - Rhinoplasty as a medicalized phenomenon: a 25-center survey on quality of life
      before and after cosmetic rhinoplasty.
AB  - BACKGROUND: Cosmetic surgery, including rhinoplasty, has been dramatically
      increasing in Iran through the last two decades. It is performed mainly on the
      youth for the purpose of beauty, an area not directly related to medicine but
      strongly medicalized. This study aimed to explore the effects of rhinoplasty on
      the quality of life experienced by individuals who have undergone the surgery.
      METHODS: From all the plastic surgery clinics in Teheran, 25 were selected
      randomly as sites for the study. In the next step, 110 patients who had undergone
      rhinoplasty were selected randomly from these clinics. Only patients whose
      surgery had been performed 3 to 18 months before the interview were included in
      the statistical population. Data were collected through a Likert-type
      questionnaire that queries three major quality-of-life dimensions: general
      benefit, social support, and physical health. The collected data were analyzed by
      SPSS. RESULTS: The mean scores for quality of life before and after surgery were
      66.54 and 61.11, respectively. The difference was statistically significant (P =
      0.008), showing a decline in quality of life after rhinoplasty. Whereas the mean
      score for social support and physical health decreased, the score for general
      benefit increased after the surgery. The main motivating factors for surgery were
      external factors (e.g., friends, family). In addition, the date of the surgery
      and the time of the interview were positively correlated. In other words, the
      longer the time since surgery, the greater was the increase in the patients'
      satisfaction and quality of life. CONCLUSIONS: The overall quality of life among
      the statistical population decreased. This could be attributed to unnecessary
      surgeries, medical errors, and performance of rhinoplasty because of its
      recognized popularity. The reduction in social support may have resulted from
      unacceptable consequences of rhinoplasty, particularly in terms of appearance,
      and reactions of family and peer group. The physical health of the respondents
      was negatively affected by rhinoplasty. Malfunction of the upper respiratory
      system after rhinoplasty is a known main reason for the negative effect of
      rhinoplasty on the quality of life. Correlations between the times of the surgery
      and the interview suggest a long-term rather than an immediate assessment of
      effects that such surgeries have on the quality of life. LEVEL OF EVIDENCE V:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      http://www.springer.com/00266.

PMID- 24902904
TI  - RIPK1 both positively and negatively regulates RIPK3 oligomerization and
      necroptosis.
AB  - Necroptosis is a form of programmed cell death that depends on the activation of
      receptor interacting protein kinase-1 (RIPK1) and RIPK3 by receptors such as
      tumor necrosis factor (TNF) receptor-1. Structural studies indicate that
      activation of RIPK3 by RIPK1 involves the formation of oligomers via interactions
      of the RIP homotypic interaction motif (RHIM) domains shared by both proteins;
      however, the molecular mechanisms by which this occurs are not fully understood.
      To gain insight into this process, we constructed versions of RIPK3 that could be
      induced to dimerize or oligomerize in response to a synthetic drug. Using this
      system, we find that although the formation of RIPK3 dimers is itself
      insufficient to trigger cell death, this dimerization seeds a RHIM-dependent
      complex, the propagation and stability of which is controlled by caspase-8 and
      RIPK1. Consistent with this idea, we find that chemically enforced
      oligomerization of RIPK3 is sufficient to induce necroptosis, independent of the
      presence of the RHIM domain, TNF stimulation or RIPK1 activity. Further, although
      RIPK1 contributes to TNF-mediated RIPK3 activation, we find that RIPK1
      intrinsically suppresses spontaneous RIPK3 activation in the cytosol by
      controlling RIPK3 oligomerization. Cells lacking RIPK1 undergo increased
      spontaneous RIPK3-dependent death on accumulation of the RIPK3 protein, while
      cells containing a chemically inhibited or catalytically inactive form of RIPK1
      are protected from this form of death. Together, these data indicate that RIPK1
      can activate RIPK3 in response to receptor signaling, but also acts as a negative
      regulator of spontaneous RIPK3 activation in the cytosol. 

PMID- 24902907
TI  - Closed rhinoplasty with open approach advantages: extended intranasal incisions
      and tip rearrangement sutures.
AB  - BACKGROUND: Two main well-known approaches are used in rhinoplasty: open and
      closed techniques. This study aimed to define two new tip suture modifications
      that enhance and stabilize tip shape, projection, and position through an
      extended infracartilaginous incision with an open rhinoplasty exposure. METHODS:
      This study investigated 56 consecutive primary rhinoplasty patients 18-51 years
      of age (mean age 27.8 years) who underwent surgery between June 2011 and June
      2012 and had at least a 1-year postoperative follow-up period. Rhinoplasty was
      performed through an extended infracartilaginous incision with an open exposure.
      Transdomal suture modification for columella-lobular angle augmentation and a
      footplate repositioning suture for tip projection (and position) enhancement also
      were defined. A postoperative satisfaction survey was applied to all the patients
      at their 1-year follow-up visit. RESULTS: The postoperative satisfaction rate was
      96 %. The nasal tip positions and projections of the patients were fine and
      stable in all the patients after a 1-year postoperative period. At this writing,
      no over- or underprojection, supratip deformity, saddle-nose deformity, or dorsal
      surface irregularities have been encountered. Representative cases are displayed.
      CONCLUSION: This study defined two new tip suture techniques and combined them
      with an extended infracartilaginous incision. Also, control of the entire nose
      and nasal valve area was possible through this incision. LEVEL OF EVIDENCE V:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24902908
TI  - Time spent before the mast: an emerging role for mast cells in prosthetic breast
      implant capsule formation.

PMID- 24902909
TI  - Wide-undermining neck liposuction: tips and tricks for good results.
AB  - BACKGROUND: Neck rejuvenation is one of the most sought after procedures in the
      restoration of the facial contour. Numerous techniques to improve the aesthetic
      outcome and reduce downtime have been described. In our experience, wide
      undermining and local anesthesia are key to obtaining good results in selected
      patients who want a quick recovery. This article presents our experience with
      liposuction of the neck and proposes some tips and tricks to master wide
      undermining neck liposuction. METHODS: From January 2005 to September 2012, a
      total of 118 patients (34 males, 84 females) underwent neck liposuction. Patient
      selection was based mainly on age and neck-aging features. The procedure was
      performed with the patients under local anesthesia. A wide rhomboid-shaped skin
      undermining of the submandibular and neck area was performed and a very thin fat
      layer was preserved. Dressing was applied for 3 days. RESULTS: Improvement of the
      neck's contour was observed in all patients. Redefinition of the
      cervicomandibular angle and skin redraping of the cervical area occurred in all
      cases. No further touch-ups were needed. Edema and ecchymosis resolved in a few
      days. No major complications were observed. CONCLUSIONS: Our results show that
      wide-undermining neck liposuction performed under local anesthesia is an
      effective and safe procedure. Patient selection based on age and anatomical
      features was fundamental to obtain impressive improvement of neck contour. LEVEL
      OF EVIDENCE V: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24902910
TI  - Self-mutilation by a patient with borderline personality disorder.
AB  - We present an unusual insatiable aesthetic/plastic surgery patient with
      borderline personality disorder (BPD) who removed her upper eyelids by herself
      after we rejected her request for revision blepharoplasty. This impulsive self
      injury was attributed to anxiety from what the patient considered to be
      abandonment by the surgeon. Even after the eyelid defects were successfully
      treated, the patient requested several other revisions, including tattoo removal.
      Compared with other mental disorders, including body dysmorphic disorder,
      preoccupation with appearance in BPD is less profound and shifts from one body
      part to another. In an aesthetic and plastic surgery practice, a different
      psychiatric approach should be used for individuals with BPD, and the proper
      timing for a psychiatric referral should be established. LEVEL OF EVIDENCE V:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24902911
TI  - Meta-analysis of the safety and factors contributing to complications of MS-TRAM,
      DIEP, and SIEA flaps for breast reconstruction.
AB  - BACKGROUND: Muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM),
      deep inferior epigastric perforator (DIEP), and superficial inferior epigastric
      artery (SIEA) flaps have been increasingly adopted for breast reconstruction.
      However, their safety, patient satisfaction with them, and factors contributing
      to complications are not well understood. METHODS: PubMed, MEDLINE, EMBASE, and
      The Cochrane Library were searched to identify eligible studies for inclusion in
      our analysis. The complication rates of and patient satisfaction rates with the
      flaps were measured as the outcome, and factors contributing to complications and
      patient satisfaction were also studied. The data were extracted, and pooled
      relative risks (RRs) and 95 % confidence intervals (CIs) were calculated.
      RESULTS: Thirteen studies involving 1,843 patients met the inclusion criteria.
      The results of the meta-analysis showed that patients with MS-TRAM had a higher
      rate of abdominal hernias (RR 2.354, 95 % CI 1.154-4.802, P = 0.019) and a lower
      rate of fat necrosis (RR 0.502, 95 % CI 0.347-0.727, P = 0.000) than patients
      with DIEP. In addition, there was no significant difference between MS-TRAM and
      DIEP with respect to other complications (P > 0.05), between MS-TRAM and DIEP
      with respect to patient satisfaction (P = 0.923), and between DIEP and SIEA with
      respect to complication rates (P = 0.377). The complication rates of MS-TRAM,
      DIEP, and SIEA were 25.6, 27.9, and 26.7 %, respectively. Diabetes mellitus (P =
      0.078) influenced the complication rate of MS-TRAM, and obesity (P = 0.086) and
      diabetes mellitus (P = 0.110) were the potential factors correlated with
      complications with DIEP flaps. CONCLUSION: There were no obvious differences in
      the overall incidence of complications between MS-TRAM and DIEP and between DIEP
      and SIEA. In addition, the patient satisfaction rates of MS-TRAM and DIEP were
      similar. However, MS-TRAM showed a higher rate of abdominal hernias and a lower
      rate of fat necrosis than DIEP. Obesity and diabetes mellitus were potential
      factors associated with the incidence of complications. Additional multicenter,
      large-sample-size, randomized controlled trials with long-term follow-up visits
      are necessary. LEVEL OF EVIDENCE III: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 24902912
TI  - Reconstruction for extensive groin hidradenitis suppurativa using a combination
      of inferior abdominal flap and medial thigh-lift: a case report.
AB  - Various methods for reconstructing hidradenitis suppurativa of the groin have
      been reported. However, it is difficult to attain favorable results both
      aesthetically and functionally. This report describes a case in which a defect
      was reconstructed using a combination of inferior abdominal flap and medial thigh
      lift after radical excision of extensive groin hidradenitis suppurativa. A 37
      year-old woman patient underwent radical excision of bilateral groin hidradenitis
      suppurativa. After the excision, an inferior abdominal flap and bilateral medial
      thigh flaps were created and advanced to close the defect. The operative
      procedure was simple and did not require a donor site. The postoperative scar
      coincided with the inguinal folds and was concealed by undergarments. No
      functional disorder remained. Reconstruction for extensive groin hidradenitis
      suppurativa using this method can attain good aesthetic and functional results.
      The combination of inferior abdominal flap and medial thigh-lift is potentially a
      useful option for reconstruction of extensive groin hidradenitis suppurativa.
      LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 24902913
TI  - Informed consent in Italy-traditional versus the law: a gordian knot.

PMID- 24902914
TI  - Correction of tuberous breasts using the unfolded subareolar gland flap.
AB  - In this retrospective study, the authors present 12 years of experience using a
      modified Puckett's technique with a double unfolded strictly subareolar glandular
      flap for surgical correction of the deformity known as "tuberous breast." In
      1976, Rees and Aston documented this congenital malformation of the mammary
      glands in women. Its cause is unknown, and it affects adolescent girls with
      varying severity uni- or bilaterally. The condition is characterized by a lack of
      development, primarily in the lower quadrants of the breast plus a rising of the
      inframammary fold, together with herniation and increased diameter of the areola.
      Many varied surgical techniques for correction of this malformation in its
      different degrees of severity have been documented in the available literature.
      This study examined the treatment of 42 breasts in 26 patients with a high
      percentage of full correction of the deformity. The advantages and achievements
      of the double unfolded strictly subareolar glandular flap include restructuring
      of the breast's lower pole in volume, length, and shape; reduction and even
      removal of the double-bubble effect as the flap covers the implant fitted;
      lowering of inframammary fold height; and correction of areola size and
      herniation. The procedure is performed through a hemi- or periareolar incision.
      The technique is versatile for managing the different variations of tuberous
      breasts, making it another interesting option for correction of the deformity.
      Level of Evidence IV This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 24902915
TI  - Repair of refractory wounds through grafting of artificial dermis and autologous
      epidermis aided by vacuum-assisted closure.
AB  - BACKGROUND: This study aimed to investigate the clinical efficacy of vacuum
      assisted closure (VAC) combined with grafting of artificial dermis and autologous
      epidermis in the repair of refractory wounds. METHODS: Patients with refractory
      wounds underwent debridement. Then the VAC device was used to culture wound
      granulation tissue. After the wound granulation tissue began to grow, artificial
      dermis was grafted on the wounds with VAC treatment. Then autologous epidermis
      was grafted on the artificial dermis to repair the wounds after survival of the
      artificial epidermis. The study mainly observed length of the hospital stay,
      survival of the artificial dermis, time required for culture of the granulation
      tissue using VAC before grafting of the artificial dermis, survival time of the
      artificial dermis, survival conditions of the autologous epidermis, influence on
      functions of a healed wound at a functional part, healing conditions of donor
      sites, and recurrence conditions of the wounds. RESULTS: Healing was successful
      for 22 patients (95.7%), but treatment failed for 1 child. The 22 patients were
      followed up for 6 to 24 months. According to follow-up findings, the skin grafts
      had good color and a soft texture. They were wear resistant and posed no
      influence on function. The appearance of the final results was the same as that
      of the full-thickness skin graft. Mild or no pigmentation and no scar formation
      occurred at the donor sites, and the wounds did not recur. CONCLUSION: Vacuum
      assisted closure combined with grafting of artificial dermis and autologous
      epidermis is an effective means for repairing refractory wounds and is worth
      clinical popularizing and application. LEVEL OF EVIDENCE V: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 24902916
TI  - The free-nipple breast-reduction technique performed with transfer of the nipple
      areola complex over the superior or superomedial pedicles.
AB  - BACKGROUND: Although the free-nipple breast-reduction technique is essentially an
      amputation, achieving aesthetic results still is important. The authors present
      their technique for free nipple-areola complex (NAC) transfer over the
      superomedial or superior pedicle full-thickness flaps in patients for whom a free
      nipple technique is inevitable due to certain risk factors. METHODS: The study
      included 25 patients who underwent surgery with the aforementioned method for
      addressing severe gigantomastia. The patients had a mean age of 43 years (range
      34-59 years) and a mean body mass index (BMI) of 35.8 kg/m(2) (range 28-42
      kg/m(2)). During the operation, the NAC was elevated as a full-thickness skin
      graft, then transposed to the superior or superomedial pedicles, which had been
      planned previously. The subsequent stages of the operation thus became a Wise
      pattern breast reduction. RESULTS: The mean resection per breast was 1,815 g
      (range 1,620-2,410 g). Breast projection, shape, and areolar pigmentation were
      assessed during the follow-up visit. One patient experienced a partial loss of
      the NAC graft, which healed secondarily, and three patients experienced a patchy
      hypopigmentation of the NAC. Breast projection and conical structure were
      observed to be preserved during the follow-up period. CONCLUSIONS: The modified
      free-nipple technique aimed to convert the reduction procedure to a technique
      similar to pedicle methods, yielding successful results during the early phases.
      The full-thickness flap constructed in this way provides more fullness and a
      maximum contribution to projection in patients who will inevitably undergo breast
      reduction with the free-nipple method. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24902917
TI  - Saddle-nose deformity repair with microplate-adapted costal cartilage.
AB  - Nasal deformities affecting the bone and lower two-thirds of the nose due to the
      loss of septal height and tip support are defined as "saddle-nose" deformity.
      Reconstruction of a saddle-nose deformity essentially necessitates structural
      grafting. This article presents an alternative approach for correction of saddle
      nose deformity using a microplate and costal cartilage. The results are compared
      with those of the previously applied costal cartilage repair methods. Between
      2004 and 2013, 16 patients were treated with costal cartilage autografts. Of
      these 16 patients, 7 were treated with a microplate and costal cartilage
      autograft combination, 4 were treated with a costal cartilage autograft and
      Kirschner (K)-wire, and 5 were treated with onlay costal cartilage grafts. The
      mean follow-up periods were 16 months for group treated with microplate-adapted
      autologous costal cartilage, 12 months for the group treated with K-wire and
      autologous costal cartilage, and 16 months for the group treated with onlay
      costal cartilage. The patients treated with K-wire inserted cartilages and the
      patients treated onlay dorsal costal cartilages encountered complications such as
      extrusion of the wire and warping, respectively. The seven patients treated with
      microplate and dorsal onlay costal cartilage graft did not experience any
      infection, warping, or extrusion complication. The warping tendency of the costal
      cartilage autograft can be efficiently prevented without a prominent complication
      risk by using microplate-adapted costal cartilage grafts. LEVEL OF EVIDENCE IV:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24902918
TI  - Clear to cloudy: silicone breast implants in vivo.

PMID- 24902919
TI  - Pseudolymphoma on tattoos.

PMID- 24902921
TI  - Blinding strategies in the conduct and reporting of a randomized placebo
      controlled device trial.
AB  - BACKGROUND: Blinding is a fundamental design strengthening feature in randomized
      clinical trials. Blinding is particularly important in trials whose outcome
      measures include subjective assessment of signs and symptoms, such as trials
      investigating the post-thrombotic syndrome, a frequent chronic complication of
      deep vein thrombosis. PURPOSE: To determine whether strategies used to blind site
      investigators, research coordinators and patients were successful in a specific
      device trial, a multicenter trial of active versus placebo elastic compression
      stockings worn for 2 years to prevent post-thrombotic syndrome in patients with a
      first deep vein thrombosis (the SOX Trial). METHODS: Patients were randomized to
      the active or placebo stocking intervention, which were indistinguishable in
      appearance at baseline. Replacement stockings were shipped directly to patients'
      homes and were not worn to any of the study visits during the study. Guesstimates
      of treatment group assignment were completed by site investigators, research
      coordinators and patients at the end of study follow-up. Statistical assessments
      of blinding were performed using the James and Bang blinding indices. RESULTS:
      Overall rates of correct responses were 10.4% for site investigators, 17.8% for
      research coordinators and 29.4% for patients. James blinding index values suggest
      that blinding was achieved for site investigators, research coordinators and
      patients. The treatment specific Bang blinding index values suggest that blinding
      was achieved for site investigators and research coordinators, but detected
      possible unblinding and opposite guess for patients in the active and placebo
      elastic compression stocking groups, respectively. LIMITATIONS: Post-study
      assessment of blinding, as was done for the SOX Trial, cannot distinguish between
      degree of blinding and hunches about an intervention's efficacy. However, as
      rates of post-thrombotic syndrome along with adverse events in the SOX Trial were
      similar between treatment groups, it is unlikely that hunches would have
      interfered with our end-of-trial assessment for blinding. CONCLUSION: Blinding
      strategies used in our trial were successful overall and appeared to be most
      effective for site investigators and research coordinators. For patients, there
      may have been some degree of unblinding in the active stocking group. However, as
      the trial results were negative with active elastic compression stocking showing
      no benefit over placebo elastic compression stocking, this potential unblinding
      has minimal impact on the overall conclusions of the trial.

PMID- 24902922
TI  - Optimization of behavioral dynamic treatment regimens based on the sequential,
      multiple assignment, randomized trial (SMART).
AB  - BACKGROUND AND PURPOSE: A behavioral intervention is a program aimed at modifying
      behavior for the purpose of treating or preventing disease, promoting health,
      and/or enhancing well-being. Many behavioral interventions are dynamic treatment
      regimens, that is, sequential, individualized multicomponent interventions in
      which the intensity and/or type of treatment is varied in response to the needs
      and progress of the individual participant. The multiphase optimization strategy
      (MOST) is a comprehensive framework for development, optimization, and evaluation
      of behavioral interventions, including dynamic treatment regimens. The objective
      of optimization is to make dynamic treatment regimens more effective, efficient,
      scalable, and sustainable. An important tool for optimization of dynamic
      treatment regimens is the sequential, multiple assignment, randomized trial
      (SMART). The purpose of this article is to discuss how to develop optimized
      dynamic treatment regimens within the MOST framework. METHODS AND RESULTS: The
      article discusses the preparation, optimization, and evaluation phases of MOST.
      It is shown how MOST can be used to develop a dynamic treatment regimen to meet a
      prespecified optimization criterion. The SMART is an efficient experimental
      design for gathering the information needed to optimize a dynamic treatment
      regimen within MOST. One signature feature of the SMART is that randomization
      takes place at more than one point in time. CONCLUSION: MOST and SMART can be
      used to develop optimized dynamic treatment regimens that will have a greater
      public health impact.

PMID- 24902920
TI  - The design and rationale of a multicenter clinical trial comparing two strategies
      for control of systolic blood pressure: the Systolic Blood Pressure Intervention
      Trial (SPRINT).
AB  - BACKGROUND: High blood pressure is an important public health concern because it
      is highly prevalent and a risk factor for adverse health outcomes, including
      coronary heart disease, stroke, decompensated heart failure, chronic kidney
      disease, and decline in cognitive function. Observational studies show a
      progressive increase in risk associated with blood pressure above 115/75 mm Hg.
      Prior research has shown that reducing elevated systolic blood pressure lowers
      the risk of subsequent clinical complications from cardiovascular disease.
      However, the optimal systolic blood pressure to reduce blood pressure-related
      adverse outcomes is unclear, and the benefit of treating to a level of systolic
      blood pressure well below 140 mm Hg has not been proven in a large, definitive
      clinical trial. PURPOSE: To describe the design considerations of the Systolic
      Blood Pressure Intervention Trial (SPRINT) and the baseline characteristics of
      trial participants. METHODS: The Systolic Blood Pressure Intervention Trial is a
      multicenter, randomized, controlled trial that compares two strategies for
      treating systolic blood pressure: one targets the standard target of <140 mm Hg,
      and the other targets a more intensive target of <120 mm Hg. Enrollment focused
      on volunteers of age >=50 years (no upper limit) with an average baseline
      systolic blood pressure >=130 mm Hg and evidence of cardiovascular disease,
      chronic kidney disease, 10-year Framingham cardiovascular disease risk score
      >=15%, or age >=75 years. The Systolic Blood Pressure Intervention Trial
      recruitment also targeted three pre-specified subgroups: participants with
      chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73
      m(2)), participants with a history of cardiovascular disease, and participants 75
      years of age or older. The primary outcome is first the occurrence of a
      myocardial infarction (MI), acute coronary syndrome, stroke, heart failure, or
      cardiovascular disease death. Secondary outcomes include all-cause mortality,
      decline in kidney function or development of end-stage renal disease, incident
      dementia, decline in cognitive function, and small-vessel cerebral ischemic
      disease. RESULTS: Between 8 November 2010 and 15 March 2013, Systolic Blood
      Pressure Intervention Trial recruited and randomized 9361 people at 102 clinics,
      including 3331 women, 2648 with chronic kidney disease, 1877 with a history of
      cardiovascular disease, 3962 minorities, and 2636 >=75 years of age. LIMITATIONS:
      Although the overall recruitment target was met, the numbers recruited in the
      high-risk subgroups were lower than planned. CONCLUSIONS: The Systolic Blood
      Pressure Intervention Trial will provide important information on the risks and
      benefits of intensive blood pressure treatment targets in a diverse sample of
      high-risk participants, including those with prior cardiovascular disease,
      chronic kidney disease, and those aged >=75 years.

PMID- 24902923
TI  - Organizational and physician factors associated with patient enrollment in cancer
      clinical trials.
AB  - BACKGROUND: Our purpose was to identify physicians' individual characteristics,
      attitudes, and organizational contextual factors associated with higher
      enrollment of patients in cancer clinical trials among physician participants in
      the National Cancer Institute's Community Clinical Oncology Program (CCOP). We
      hypothesized that physicians' individual characteristics, such as age, medical
      specialty, tenure, CCOP organizational factors (i.e. policies and procedures to
      encourage enrollment), and attitudes toward participating in CCOP would directly
      determine enrollment. We also hypothesized that physicians' characteristics and
      CCOP organizational factors would influence physicians' attitudes toward
      participating in CCOP, which in turn would predict enrollment. METHODS: We
      evaluated enrollment in National Cancer Institute-sponsored cancer clinical
      trials in 2011 among 481 physician participants using Structural Equation
      Modeling. The data sources include CCOP Annual Progress Reports, two surveys of
      CCOP administrators and physician participants, and the American Medical
      Association Masterfile. RESULTS: Physicians with more positive attitudes toward
      participating in CCOP enrolled more patients than physicians with less positive
      attitudes. In addition, physicians who practiced in CCOPs that had more
      supportive policies and practices in place to encourage enrollment (i.e. offered
      trainings, provided support to screen and enroll patients, gave incentives to
      enroll patients, instituted minimum accrual expectations) also significantly
      enrolled more patients. Physician status as CCOP Principal Investigator had a
      positive direct effect on enrollment, while physician age and non-oncology
      medical specialty had negative direct effects on enrollment. Neither physicians'
      characteristics nor CCOP organizational factors indirectly influenced enrollment
      through an effect on physician attitudes. CONCLUSION: We examined whether
      individual physicians' characteristics and attitudes, as well as CCOP
      organizational factors, influenced patient enrollment in cancer clinical trials
      among CCOP physicians. Physician attitudes and CCOP organizational factors had
      positive direct effects, but not indirect effects, on physician enrollment of
      patients. Our results could be used to develop physician-directed strategies
      aimed at increasing involvement in clinical research. For example, administrators
      may want to ensure physicians have access to support staff to help screen and
      enroll patients or institute minimum accrual expectations. Our results also
      highlight the importance of recruiting physicians for volunteer clinical research
      programs whose attitudes and values align with programmatic goals. Given that
      physician involvement is a key determinant of patient enrollment in clinical
      trials, these interventions could expand the overall number of patients involved
      in cancer research. These strategies will be increasingly important as the CCOP
      network continues to evolve.

PMID- 24902924
TI  - Are missing data adequately handled in cluster randomised trials? A systematic
      review and guidelines.
AB  - BACKGROUND: Missing data are a potential source of bias, and their handling in
      the statistical analysis can have an important impact on both the likelihood and
      degree of such bias. Inadequate handling of the missing data may also result in
      invalid variance estimation. The handling of missing values is more complex in
      cluster randomised trials, but there are no reviews of practice in this field.
      OBJECTIVES: A systematic review of published trials was conducted to examine how
      missing data are reported and handled in cluster randomised trials. METHODS: We
      systematically identified cluster randomised trials, published in English in
      2011, using the National Library of Medicine (MEDLINE) via PubMed. Non-randomised
      and pilot/feasibility trials were excluded, as were reports of secondary
      analyses, interim analyses, and economic evaluations and those where no data were
      at the individual level. We extracted information on missing data and the
      statistical methods used to deal with them from a random sample of the identified
      studies. RESULTS: We included 132 trials. There was evidence of missing data in
      95 (72%). Only 32 trials reported handling missing data, 22 of them using a
      variety of single imputation techniques, 8 using multiple imputation without
      accommodating the clustering and 2 stating that their likelihood-based complete
      case analysis accounted for missing values because the data were assumed Missing
      at-Random. LIMITATIONS: The results presented in this study are based on a large
      random sample of cluster randomised trials published in 2011, identified in
      electronic searches and therefore possibly missing some trials, most likely of
      poorer quality. Also, our results are based on information in the main
      publication for each trial. These reports may omit some important information on
      the presence of, and reasons for, missing data and on the statistical methods
      used to handle them. Our extraction methods, based on published reports, could
      not distinguish between missing data in outcomes and missing data in covariates.
      This distinction may be important in determining the assumptions about the
      missing data mechanism necessary for complete case analyses to be valid.
      CONCLUSIONS: Missing data are present in the majority of cluster randomised
      trials. However, they are poorly reported, and most authors give little
      consideration to the assumptions under which their analysis will be valid. The
      majority of the methods currently used are valid under very strong assumptions
      about the missing data, whose plausibility is rarely discussed in the
      corresponding reports. This may have important consequences for the validity of
      inferences in some trials. Methods which result in valid inferences under general
      Missing-at-Random assumptions are available and should be made more accessible.

PMID- 24902925
TI  - Surface recombination and charged exciton in nanocrystal quantum dots on photonic
      crystals under two-photon excitation.
AB  - In this study, the two-photon excited fluorescence spectra from cadmium selenide
      quantum dots (QDs) on a silicon nitride photonic crystal (PhC) membrane under
      femtosecond laser irradiation were investigated. These spectra can be fit to a
      tri-Gaussian function in which one component is negative in amplitude, and in
      which the Gaussian components with positive amplitude are assigned to exciton
      emission and charged-exciton emission and that with negative amplitude is
      assigned to absorption from surface recombination. The photonic crystal enhance
      the charged-exciton emission and exciton emission and, at the same time, also the
      absorption from surface recombination. Both the charged-exciton emission and the
      surface recombination are related to Auger recombination; therefore, the photonic
      crystal controls both radiative recombination and non-radiative recombination.
      The asymmetries of the two-photon excited fluorescence spectra are due to not
      only the location of the resonant guide mode of the PhC slab but also the
      enhancement of the absorption from surface recombination by PhC. 

PMID- 24902928
TI  - Course of fever and potential infection after total joint replacement.
AB  - PURPOSE: The purpose of this study was to determine the relationship between
      fever, including different patterns of fever, and infection in patients who
      received total hip arthroplasty or knee arthroplasty (THA or TKA). METHODS: Fever
      was defined as a core body temperature >=38.0  degrees C and was further
      categorized as being (1) consecutive fever (fever lasting three or more days) or
      (2) fever with body temperature >=39  degrees C. Medical records of patients who
      underwent total joint arthroplasty (TJA) between November 2009 and February 2012
      were retrospectively examined, and those who underwent one primary TJA procedure
      were considered for inclusion. RESULTS: A total of 980 patients (TKA = 597, THA =
      383) were included. Overall, 48.2% of patients experienced fever, most commonly
      on postoperative day 1, and the maximum body temperature also most commonly
      occurred on postoperative day 1. Respiratory, urinary tract, periprosthetic, and
      any infections were significantly associated with consecutive fever (P < 0.05),
      while respiratory and any infections were significantly associated with fever
      >=39  degrees C. Multivariate analysis revealed that patients who experienced
      infection had a significantly increased risk of postoperative fever (P = 0.001).
      CONCLUSIONS: Consecutive fevers or fever >=39  degrees C after TJA may be
      indicative of postoperative infection, and testing to rule out infection should
      be performed. These results may assist in the differential diagnosis of
      postoperative fever after TJA and thus help to guide treatment. LEVEL OF
      EVIDENCE: III.

PMID- 24902926
TI  - Normative rearfoot motion during barefoot and shod walking using biplane
      fluoroscopy.
AB  - PURPOSE: The ankle rearfoot complex consists of the ankle and subtalar joints.
      This is an observational study on two test conditions of the rearfoot complex.
      Using high-speed biplane fluoroscopy, we present a method to measure rearfoot
      kinematics during normal gait and compare rearfoot kinematics between barefoot
      and shod gait. METHODS: Six male subjects completed a walking trial while biplane
      fluoroscopy images were acquired during stance phase. Bone models of the
      calcaneus and tibia were reconstructed from computed tomography images and
      aligned with the biplane fluoroscopy images. An optimization algorithm was used
      to determine the three-dimensional position of the bones and calculate rearfoot
      kinematics. RESULTS: Peak plantarflexion was higher (barefoot: 9.1 degrees ; 95%
      CI 5.2:13.0; shod: 5.7 degrees ; 95% CI 3.6:7.8; p = 0.015) and neutral
      plantar/dorsiflexion occurred later in the stance phase (barefoot: 31.1%; 95% CI
      23.6:38.6; shod: 17.7%; 95% CI 14.4:21.0; p = 0.019) during barefoot walking
      compared to shod walking. An eversion peak of 8.7 degrees  (95% CI 1.9:15.5)
      occurred at 27.8% (95% CI 18.4:37.2) of stance during barefoot walking, while
      during shod walking a brief inversion to 1.2 degrees  (95% CI -2.1:4.5; p =
      0.021) occurred earlier (11.5% of stance; 95% CI 0.2:22.8; p = 0.008) during
      stance phase. The tibia was internally rotated relative to the calcaneus
      throughout stance phase in both conditions (barefoot: 5.1 degrees  (95% CI 
      1.4:11.6); shod: 3.6 degrees  (95% CI -0.4:7.6); ns.). CONCLUSIONS: Biplane
      fluoroscopy can allow for detailed quantification of dynamic in vivo ankle
      kinematics during barefoot and shod walking conditions. This methodology could be
      used in the future to study hindfoot pathology after trauma, for congenital
      disease and after sports injuries such as instability. LEVEL OF EVIDENCE: II.

PMID- 24902929
TI  - Conventional surgical repair of traumatic rupture of the thoracic aorta.
AB  - OBJECTIVE: Traumatic rupture of the thoracic aorta is a life-threatening injury
      requiring urgent surgical intervention. Despite recent improvements in
      resuscitation and emergency operative techniques, the outcomes of patients with
      multiple injuries are still associated with a high mortality rate. We
      retrospectively examined the preoperative demographic data, associated
      complications and mortality rate of these patients. MATERIALS AND METHODS: We
      analyzed the data (1991-2009) of 18 patients with acute traumatic rupture of the
      thoracic aorta. Most patients had rupture limited to the aortic isthmus and
      severe associated injuries in other organs. The aorta was repaired by direct
      suturing, patch plasty (n = 5; 27.7 %) or graft interposition (n = 9; 50 %).
      RESULTS: The overall mortality rate was 33.3 %. All six patients who underwent
      emergency surgery within 2 h died, four intra-operatively and two
      postoperatively. The causes of the intra-operative mortality were uncontrollable
      hemorrhage and irreversible cardiac arrest due to penetrating injury of the
      thoracic aorta and intercostal arteries in three patients, and uncontrollable
      hemorrhage due to severe liver laceration in one. The surgical complications
      (42.8 %) were acute lung injury (n = 2), liver insufficiency (n = 2), acute renal
      failure (n = 1) and cerebral infarction (n = 1). No patients had postsurgical
      paraplegia. The mean period between arrival and treatment and the mean Injury
      Severity Score were significantly higher in group D than in group A. CONCLUSION:
      To improve the outcome of traumatic thoracic aortic injury, the degree of multi
      organ damage, the priority of treatment be evaluated accurately is important.

PMID- 24902930
TI  - Recurrence of juxtacortical chondrosarcoma arising on the rib.
AB  - Juxtacortical chondrosarcoma developing on the surface of a bone is quite rare.
      We report a case of juxtacortical chondrosarcoma arising on the fourth rib of a
      76-year-old man. Intraregional tumor resection was performed, but local
      recurrence was detected after 6 months. The patient underwent wide resection
      including the ribs, and reconstruction of the thoracic wall. He was released with
      a good prognosis after a year. This case emphasizes the importance of biopsy
      analysis before surgery to carefully evaluate tumor spread in the cartilage and
      performing wide resection even if the tumor is easily separated from the bone. 

PMID- 24902931
TI  - The evolving identity of otolaryngology: from otolaryngology to communication to
      human behavior.

PMID- 24902932
TI  - Traditional and atypical presentations of anxiety in youth with autism spectrum
      disorder.
AB  - We assessed anxiety consistent (i.e., "traditional") and inconsistent (i.e.,
      "atypical") with diagnostic and statistical manual (DSM) definitions in autism
      spectrum disorder (ASD). Differential relationships between traditional anxiety,
      atypical anxiety, child characteristics, anxiety predictors and ASD-symptomology
      were explored. Fifty-nine participants (7-17 years, M(age) = 10.48 years; IQ >
      60) with ASD and parents completed semi-structured interviews, self- and parent
      reports. Seventeen percent of youth presented with traditional anxiety, 15 % with
      atypical anxiety, and 31 % with both. Language ability, anxious cognitions and
      hypersensitivity predicted traditional anxiety, whereas traditional anxiety and
      ASD symptoms predicted atypical anxiety. Findings suggest youth with ASD express
      anxiety in ways similar and dissimilar to DSM definitions. Similarities support
      the presence of comorbid anxiety disorders in ASD. Whether dissimilarities are
      unique to ASD requires further examination.

PMID- 24902933
TI  - The impact of a fourteen-gene molecular assay on physician treatment decisions in
      non-small-cell lung cancer.
AB  - BACKGROUND: Five-year survival in early-stage, non-squamous, non-small-cell lung
      cancer (NSCLC) remains poor compared with other solid tumors, even after complete
      resection. Post-operative management depends on prognostic staging to identify
      individuals at highest risk for death, and therefore with the greatest need for
      further intervention. A 14-gene quantitative RT-PCR test successfully
      differentiates stage I-III NSCLC patients who are at high-, intermediate-, or low
      risk for 5-year mortality. This study assesses the impact of the assay's
      prognostic information on physician decisions regarding adjuvant chemotherapy.
      METHODS: We invited 115 physicians who ordered the test to participate in an on
      line survey. The primary outcome measure was the proportion of patients with
      different pre- and post-test chemotherapy recommendations. RESULTS: Fifty-eight
      physicians (50 %) completed the survey on 120 stage I or II NSCLC patients.
      Ninety-one patients (76 %) had stage I lung cancer; 27 (23 %), 39 (33 %), and 54
      (45 %) patients had low-, intermediate-, and high-risk scores, respectively.
      Physicians' chemotherapy recommendations were changed post-testing in 37 patients
      (30.8 %, 95 % CI 22.7-39.9 %). High-risk patients were more likely to have a
      change in treatment recommendation (44.4 %, 95 % CI 30.9-58.6 %) than low risk
      patients (3.7 %, 95 % CI 0.1-19.0 %); a substantial number of changes were
      observed in both stage I (33.0 %, 95 % CI 23.5-43.6 %) and stage II (24.1 %, 95 %
      CI 10.3-43.5 %). CONCLUSIONS: Our data show that the assay resulted in a
      significant impact on physician treatment decisions in early-stage NSCLC, and
      that the nature of treatment changes generally correlated with the test's
      assessment of risk.

PMID- 24902934
TI  - Pharmacological treatment of depression in older patients with chronic
      obstructive pulmonary disease: impact on the course of the disease and health
      outcomes.
AB  - Over 40 % of older chronic obstructive pulmonary disease (COPD) patients suffer
      from clinically significant depressive symptoms, which may interfere with their
      daily activities. Untreated depression may increase physical disability, social
      isolation, hopelessness and healthcare utilization. This review examined the
      impact of depression on the course of COPD, and the efficacy of antidepressant
      drug therapy and its implications for clinical practice. The efficacy of
      antidepressants in published trials in patients with COPD has been inconclusive.
      Specifically, there has been no clear evidence that antidepressants can induce
      remission of depression or ameliorate dyspnoea or physiological indices of COPD.
      Both selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant
      (TCA) studies conducted in depressed COPD patients have been significantly
      limited by methodological weaknesses including small sample size, sample
      heterogeneity and variability in the scales used to diagnose and monitor the
      treatment of depression. For this reason, it remains unclear which SSRIs or TCAs
      should be favoured in the treatment of depressed COPD patients and what are
      appropriate dosages and duration ranges. Simply offering antidepressant drugs to
      older depressed COPD patients is unlikely to improve their condition. Promising
      treatment strategies such as a collaborative treatment approach and cognitive
      behavioural therapy should be considered for depressed COPD patients, with or
      without antidepressant drug therapy. Further studies are needed, including large,
      randomized, controlled trials with long-term follow-up, to examine the efficacy
      of antidepressants in patients with COPD.

PMID- 24902935
TI  - The use of estimated glomerular filtration rate for dose adjustment of
      medications in the elderly.
AB  - Adverse drug effects as a consequence of inappropriate dosage are a common cause
      of hospitalization among the elderly. Older individuals are at a particular risk
      of overdosing because their kidney function decreases with advancing age and the
      elderly are often prescribed several pharmaceutical drugs. In addition, serum
      creatinine levels decrease owing to a reduction in muscle mass with age.
      Therefore, drug dosing based on the serum creatinine level only, instead of using
      assessment of the renal function, may result in overdosing of frail elderly
      patients. Renal function, i.e., the glomerular filtration rate can, with simple
      formulas, be estimated from analysis of creatinine and/or plasma cystatin C
      (eGFR). Such estimations performed with modern and validated formulas, as a rule
      present renal function normalized to the body surface area (mL/min/1.73 m(2)). A
      good estimation of how much the normal dosing interval should be prolonged, or
      the dose reduced, to obtain a desired plasma concentration of drugs that are
      mainly eliminated by glomerular filtration can be obtained by calculating the
      ratio between the patient's eGFR and the normal renal function (about 90-125
      mL/min/1.73 m(2)). Increased knowledge and use of eGFR by prescribing physicians
      will reduce the risk of overdosing drugs in the elderly.

PMID- 24902936
TI  - Neural circuits of emotion regulation: a comparison of mindfulness-based and
      cognitive reappraisal strategies.
AB  - Dealing with one's emotions is a core skill in everyday life. Effective cognitive
      control strategies have been shown to be neurobiologically represented in
      prefrontal structures regulating limbic regions. In addition to cognitive
      strategies, mindfulness-associated methods are increasingly applied in
      psychotherapy. We compared the neurobiological mechanisms of these two
      strategies, i.e. cognitive reappraisal and mindfulness, during both the cued
      expectation and perception of negative and potentially negative emotional
      pictures. Fifty-three healthy participants were examined with functional magnetic
      resonance imaging (47 participants included in analysis). Twenty-four subjects
      applied mindfulness, 23 used cognitive reappraisal. On the neurofunctional level,
      both strategies were associated with comparable activity of the medial prefrontal
      cortex and the amygdala. When expecting negative versus neutral stimuli, the
      mindfulness group showed stronger activations in ventro- and dorsolateral
      prefrontal cortex, supramarginal gyrus as well as in the left insula. During the
      perception of negative versus neutral stimuli, the two groups only differed in an
      increased activity in the caudate in the cognitive group. Altogether, both
      strategies recruited overlapping brain regions known to be involved in emotion
      regulation. This result suggests that common neural circuits are involved in the
      emotion regulation by mindfulness-based and cognitive reappraisal strategies.
      Identifying differential activations being associated with the two strategies in
      this study might be one step towards a better understanding of differential
      mechanisms of change underlying frequently used psychotherapeutic interventions. 

PMID- 24902937
TI  - A case of severe aortic valve stenosis including triple-vessel ischemic heart
      disease in which multidisciplinary percutaneous coronary intervention and balloon
      aortic valvuloplasty relieved low cardiac output syndrome.
AB  - The patient was an 80-year-old man with low cardiac output syndrome associated
      with triple-vessel ischemic heart disease and severe aortic stenosis (AS).
      Deeming the patient unprepared for surgery because of his deteriorated general
      condition, we decided to perform revascularization with a percutaneous coronary
      intervention associated with intra-aortic balloon pump (IABP) and treat the
      severe AS with percutaneous balloon aortic valvuloplasty (BAV). Complete
      revascularization was successfully achieved and BAV was performed, improving the
      aortic valve area from 0.58 to 0.92 cm(2) and the pressure gradient from 41 to 26
      mmHg. Postoperative hemodynamics improved, and the IABP was successfully removed.

PMID- 24902938
TI  - Equating the HBSC Family Affluence Scale across survey years: a method to account
      for item parameter drift using the Rasch model.
AB  - PURPOSE: To investigate the measurement invariance (MI) of the Family Affluence
      Scale (FAS) measured in the Health Behavior in School-aged Children (HBSC)
      survey, and to describe a method for equating the scale when MI is violated
      across survey years. METHODS: This study used a sample of 14,076 Norwegian and
      17,365 Scottish adolescents from the 2002, 2006 and 2010 HBSC surveys to
      investigate the MI of the FAS across survey years. Violations of MI in the form
      of differential item functioning (DIF) due to item parameter drift (IPD) were
      modeled within the Rasch framework to ensure that the FAS scores from different
      survey years remain comparable. RESULTS: The results indicate that the FAS is
      upwardly biased due to IPD in the computer item across survey years in the
      Norwegian and Scottish samples. Ignoring IPD across survey years resulted in the
      conclusion that family affluence is increasing quite consistently in Norway and
      Scotland. However, the results show that a large part of the increase in the FAS
      scores can be attributed to bias in the FAS because of IPD across time. The
      increase in the FAS was more modest in Scotland and slightly negative in Norway
      once the DIF in the computer item was accounted for in this study. CONCLUSIONS:
      When the comparison of family affluence is necessary over different HBSC survey
      years or when the longitudinal implications of family affluence are of interest,
      it is necessary to account for IPD in interpretation of changes in family
      affluence across time.

PMID- 24902939
TI  - Effect of perioperative complications and functional outcomes on health-related
      quality of life after radical prostatectomy.
AB  - PURPOSE: Radical prostatectomy is a commonly performed procedure with
      perioperative complication rates of 30 % using standardized reporting
      methodology. We aim to determine whether perioperative complications and
      functional outcomes impact quality of life 1 year after surgical treatment.
      PATIENTS AND METHODS: Quality of life, functional and oncological outcomes were
      assessed in patients who underwent open retropubic radical prostatectomy at a
      single academic institution between 2003 and 2009, preoperatively and 1 year
      after surgery using the EORTC QLQ-C30, the IIEF-5 and an institutional
      questionnaire. Perioperative complications were recorded using the Clavien-Dindo
      classification. Patients without complications were compared to patients with
      any, low- or high-grade complications. The global health score domain of the
      EORTC QLQ-C30 is reported for various oncological and functional outcomes and
      contrasted to stratified categories of complications and functional outcomes.
      RESULTS: A full dataset was available for 29.5 % (n = 856) of all patients. The
      overall complication rate was 27.5 % (235/856). A total of 307 complications were
      recorded of whom 88.9 % (273/307) were low grade. In this study, population
      global health perception did not decline after surgery (70.5 +/- 21.2 vs. 74.4 +/
      19.7; p < 0.0001). Complications showed only statistical but no clinical
      meaningful influence on global health perception as well as on functional and
      symptom scales. Patients who met combined outcome criteria experienced the best
      postoperative global health score (86.0 +/- 13.1 and 86.0 +/- 14.2). CONCLUSIONS:
      Perioperative complications and functional outcomes have a measurable impact on
      quality of life 1 year following surgery. While perioperative complications have
      a statistical effect, functional outcomes showed a clinically more profound
      effect on postoperative global health perception.

PMID- 24902940
TI  - Longitudinal quality of life data: a comparison of continuous and ordinal
      approaches.
AB  - PURPOSE: In cancer clinical trials, health-related quality of life (HRQoL) is a
      major outcome measure. It is generally assessed at specified time intervals by
      filling out a questionnaire with ordered response categories. Despite recent
      advances in the statistical methodology for handling ordinal longitudinal outcome
      data, most users keep treating HRQoL scales as continuous rather than ordinal
      variables regardless of the number of categories. The purpose of this study was
      to compare the results of analyzing HRQoL longitudinal data under both
      approaches, continuous and ordinal. METHODS: The EORTC QLQ-C30 scores of two
      EORTC randomized brain cancer clinical trials (26951 and 26981) were analyzed
      using the two approaches. In the 26951 trial, a total of 368 patients were
      randomly assigned to receive either radiotherapy (RT) or the same RT plus
      procarbazine, CCNU, and vincristine. In the 26981 trial, 573 patients were
      randomly allocated to RT or RT plus temozolomide. Comparison of the two treatment
      arms was done using methods for longitudinal quantitative and longitudinal
      ordinal data. Both statistical methods were adapted to account for missing data
      and compared in terms of statistical significance of the results (p values) but
      also with respect to data interpretation. RESULTS: Three scales, i.e., appetite
      loss, insomnia, and drowsiness, presenting four response categories ("Not at
      all", "A little", "Quite a bite", and "Very much") were analyzed in each trial.
      Both statistical methods (continuous and ordinal) showed statistically
      significant differences between the two treatments, not only globally but also at
      the same assessment time points. The magnitude of the p values, however, varied
      at some time points and was less pronounced in the ordinal approach. CONCLUSIONS:
      The analysis of the two clinical trials showed that treating the HRQoL scales by
      a quantitative or an ordinal method did not make much difference as far as
      statistical significance was concerned. The interpretation of results, however,
      was easier under the ordinal approach. Treatment effects may be more meaningful
      when expressed in terms of odds ratios than as mean values, particularly when the
      number categories is small.

PMID- 24902941
TI  - Bone health in children and adolescents with steroid-sensitive nephrotic syndrome
      assessed by DXA and QUS.
AB  - BACKGROUND: The management of steroid-sensitive nephrotic syndrome (SSNS)
      requires treatment with high-dose glucocorticoids (GCs), but GC usage causes the
      most frequent form of drug-induced osteoporosis. The aim of our study was to
      evaluate the impact of GCs on bone mineralization in patients with SSNS using two
      diagnostic tools, dual-energy X-ray densitometry (DXA) and quantitative
      ultrasound (QUS), and to compare the diagnostic efficacy of these two imaging
      tools. METHODS: A total of 30 children with SSNS (age 5.20 +/- 2.20 years) were
      evaluated at the start (T0) and after 1 (T1), 2.44 +/- 0.75 (T2, 18 patients) and
      5.96 +/- 2.33 years (T4, 12 patients) of GC treatment. Patients who stopped at T2
      were also evaluated at the 1-year timepoint after ceasing GC treatment (T3).
      RESULTS: Of the patients assessed at T2, 11 had bone mineralization at the lower
      limit of normal versus those at T0 and T1, with bone mineralization rescue at the
      1-year timepoint after GC discontinuation. At T4, 6/12 patients had densitometric
      parameters at the lower limit of normal values, and 3/12 patients showed reduced
      bone mineralization. The parameters derived from measurements of DXA and QUS were
      significantly related to each timepoint. CONCLUSIONS: Patients with SSNS
      receiving GC therapy undergo bone status alteration related to the dosage and
      duration of the therapy. In terms of diagnostic efficacy, DXA and QUS were
      comparable, indicating that QUS is a reliable tool to evaluate bone health in
      children with SSNS.

PMID- 24902942
TI  - Phosphate homeostasis in Bartter syndrome: a case-control study.
AB  - BACKGROUND: Bartter patients may be hypercalciuric. Additional abnormalities in
      the metabolism of calcium, phosphate, and calciotropic hormones have occasionally
      been reported. METHODS: The metabolism of calcium, phosphate, and calciotropic
      hormones was investigated in 15 patients with Bartter syndrome and 15 healthy
      subjects. RESULTS: Compared to the controls, Bartter patients had significantly
      reduced plasma phosphate {mean [interquartile range]:1.29 [1.16-1.46] vs. 1.61
      [1.54-1.67] mmol/L} and maximal tubular phosphate reabsorption (1.16 [1.00-1.35]
      vs. 1.41 [1.37-1.47] mmol/L) and significantly increased parathyroid hormone
      (PTH) level (6.1 [4.5-7.7] vs. 2.8 [2.2-4.4] pmol/L). However, patients and
      controls did not differ in blood calcium, 25-hydroxyvitamin D, alkaline
      phosphatase, and osteocalcin levels. In patients, an inverse correlation (P <
      0.05) was noted between total plasma calcium or glomerular filtration rate and
      PTH concentration. A positive correlation was also noted between PTH and
      osteocalcin concentrations (P < 0.005), as well as between chloriduria or
      natriuria and phosphaturia (P < 0.001). No correlation was noted between
      calciuria and PTH concentration or between urinary or circulating phosphate and
      PTH. CONCLUSIONS: The results of this study demonstrate a tendency towards renal
      phosphate wasting and elevated circulating PTH levels in Bartter patients.

PMID- 24902943
TI  - Clinico-pathological correlations of congenital and infantile nephrotic syndrome
      over twenty years.
AB  - BACKGROUND: Nephrotic syndrome (NS) presenting early in life is caused by
      heterogeneous glomerular diseases. We retrospectively evaluated whether
      histological diagnosis in children presenting with NS in the first year of life
      predicts remission or progression to end-stage kidney disease (ESKD). METHODS:
      This is a single centre retrospective review of all children diagnosed with NS
      before one year of age between 1990 and 2009. All subjects had a renal biopsy,
      which was independently blindly reviewed by a single renal pathologist for the
      purpose of this study. RESULTS: Forty-nine children (25 female) who presented at
      0.1-11.6 (median 1.6) months were included with 31 presenting within the first
      three months of life. Histopathological review diagnostic categories were; 13
      Mesangial proliferative glomerulopathy (MesGN), 12 Focal and segmental
      glomerulosclerosis (FSGS), 11 Finnish type changes, eight Diffuse Mesangial
      Sclerosis (DMS), three Minimal change disease (MCD) and one each of Dense Deposit
      Disease (DDD) and Membranous nephropathy. Two children died from haemorrhagic
      complications of the biopsy. Eight children achieved remission (four MesGN, one
      Finnish type changes, one FSGS, one MCD and one membranous) with patient and
      renal survival of 73 % and 43 %, respectively, at follow-up duration of 5-222
      (median 73) months (with five lost to follow-up). All children with Finnish-type
      histopathological changes presented within five months of age. Due to the
      historical nature of the cohort, genetic testing was only available for 14
      children, nine of whom had an identifiable genetic basis (seven NPHS1, one PLCE1
      and one ITGA3) with none of these nine children achieving remission. All of them
      had presented within four months of age and required renal replacement therapy,
      and two died. CONCLUSIONS: Histopathological findings are varied in children
      presenting with NS early in life. Whilst groups of histological patterns of
      disease are associated with differing outcomes, accurate prediction of disease
      course in a specific case is difficult and more widespread genetic testing may
      improve the understanding of this group of diseases and their optimal management.

PMID- 24902944
TI  - The glucocorticoid dexamethasone inhibits U937 cell adhesion and neutrophil
      release via RhoA/ROCK1-dependent and independent pathways.
AB  - AIMS: The aim of the present study was to investigate the role of the Ras homolog
      family member A (RhoA)/Rho-associated coiled-coil-containing protein kinase 1
      (ROCK1) signaling pathway in the inhibition of inflammatory responses by the
      glucocorticoid dexamethasone (Dex). METHODS: The inhibitory effects of Dex and
      Rho-kinase inhibitor fasudil (Fas) on phorbol ester-induced release of O2(-) and
      MPO from neutrophils and on U937 mononuclear cell adhesion were examined along
      with the expression and activity levels of RhoA and ROCK1. RESULTS: High doses of
      Dex rapidly inhibited the release of O2(-) and myeloperoxidase (MPO) from
      neutrophils and the adhesion of U937 cells, while Fas was only found to inhibit
      U937 cell adhesion. Additionally, Dex suppressed ROCK1 activity. However, Dex had
      no effects on ROCK1 or RhoA expression levels or on RhoA activity. Neither the
      glucocorticoid receptor antagonist mifepristone (RU-486) nor the protein
      synthesis inhibitor cycloheximide (CHX) was able to suppress the effects of Dex
      (p>0.05). CONCLUSIONS: The present findings indicate that Dex suppressed
      neutrophil release through ROCK1-independent mechanisms and inhibited the
      adhesion of U937 mononuclear cells through ROCK1-dependent non-genomic mechanisms
      that did not involve RhoA.

PMID- 24902945
TI  - A case of hyperemesis in bulimia nervosa.
AB  - Bulimia nervosa is an eating disorder defined by recurrent episodes of binge
      eating followed by compensatory behaviors, primarily self-induced vomiting. Most
      common complications are due to purge behaviors and are frequently responsible
      for hospitalization. These include electrolyte disturbances, dehydration,
      hypovolemia, stomatitis, esophageal diseases, and functional impairment of the
      colon. However, an obstruction-like syndrome has never been reported. We report
      the case of a middle-age woman suffering from bulimia nervosa and referring at
      the emergency department with a 7-day story of hyperemesis responsible for an
      acute renal failure. During hospitalization, after the most important and common
      medical causes of hyperemesis were excluded, an upper gastrointestinal endoscopy
      was performed. The endoscopist reported the presence of an impressive bezoar,
      which underwent to mechanical fragmentation and biopsy sampling, revealing it was
      made up exclusively of liquorice wheels. An endoscopy performed few days after
      showed the complete dissolution of the bezoar, and the patient was discharged
      without any further gastrointestinal complaint.

PMID- 24902946
TI  - In vivo dynamic loading reduces bone growth without histomorphometric changes of
      the growth plate.
AB  - This in vivo study aimed at investigating the effects of dynamic compression on
      the growth plate. Rats (28 days old) were divided into three dynamically loaded
      groups, compared with two groups (control, sham). A device was implanted on the
      6th and 8th caudal vertebrae for 15 days. Controls (n = 4) did not undergo
      surgery. Shams (n = 4) were operated but not loaded. Dynamic groups had
      sinusoidal compression with a mean value of 0.2 MPa: 1.0 Hz and +/- 0.06 MPa
      (group a, n = 4); 0.1 Hz and +/- 0.2 MPa (group b, n = 4); 1.0 Hz and +/- 0.14
      MPa (group c, n = 3). Growth rates (um/day) of dynamic groups (a) and (b) were
      lower than shams (p < 0.01). Growth plate heights, hypertrophic cell heights and
      proliferative cell counts per column did not change in dynamic (a) and (b) groups
      compared with shams (p > 0.01). Rats from dynamic group (c) had repeated
      inflammations damaging tissues; consequently, their analysis was unachievable.
      Increasing magnitude or frequency leads to growth reduction without
      histomorphometric changes. However, the combined augmentation of magnitude and
      frequency alter drastically growth plate integrity. Appropriate loading
      parameters could be leveraged for developing novel growth modulation implants to
      treat skeletal deformities.

PMID- 24902947
TI  - Carbon storage in recombinant Escherichia coli during growth on glycerol and
      lactic acid.
AB  - A fed-batch process was studied with lactate and glycerol supply in the growth
      phase and glycerol supply during L-phenylalanine production with recombinant E.
      coli K-12. Lactic acid feeding was necessary for growth because the genes
      encoding the PEP-consuming pyruvate kinase isoenzymes (pykA, pykF) have been
      deleted. An unexpected glucose efflux (67.6 +/- 2.3 mgGlucose  gCDW (-1) ) was
      measured after the cells were harvested and resuspended in a mineral medium for
      metabolic perturbation experiments. As the efflux prohibited the application of
      these experiments, characterization of intracellular carbon storage was
      necessary. Therefore, two genetically engineered strains (one lacking glycogen
      metabolism and another additionally lacking trehalose synthesis) were applied in
      the fed-batch process. Trehalose synthesis and accumulation from lactate was
      clearly identified as the source for glucose efflux after cell harvest and
      resuspension. Cultivations of strains with active pyruvate kinase successfully
      identified lactate as the carbon source causing intracellular trehalose storage.
      The usage of glycerol as sole carbon source during the whole process enabled an
      improved process performance and inhibited trehalose accumulation. Overall, this
      setup allows the application of perturbation experiments.

PMID- 24902949
TI  - MR-guided laser-induced thermotherapy in ex vivo porcine kidney: comparison of
      four different imaging sequences.
AB  - PURPOSE: To evaluate the clinical value of different magnetic resonance imaging
      (MRI) sequences for a real-time thermo-monitoring during laser-induced
      thermotherapy (LITT) in kidneys. METHODS: Twenty-eight ex vivo pig kidneys were
      treated with laser ablation under MR guidance in a high-field MR scanner
      (Magnetom Espree or Avanto Fit, Siemens, Germany). For the thermal ablation of
      the kidney, a neodymium yttrium-aluminum-garnet (Nd:YAG) laser was used in
      combination with a special protective catheter (length 43 cm, 4 French) which is
      sealed at the distal end. First, ablation was performed for 7, 10, and 13 minutes
      using FLASH sequences for investigation of time-dependent growth of lesion size.
      In the second step, we evaluated the optimal imaging sequence during a 7 minutes
      ablation of the kidney and after cooling using four different MR sequences
      (Haste, FLASH, radial VIBE, and Caipirinha DIXON). RESULTS: Macroscopic lesion
      volume increased from 3,784 +/- 1,525 mm(3) to 7,683 +/- 5,756 mm(3) after the
      ablation from 7 to 13 minutes and MR volume ranged from 2,107 +/- 1,674 mm(3) to
      2,934 +/- 1,549 mm(3) after the ablation from 7 to 13 minutes. During ablation,
      FLASH (132 +/- 34%) and radial VIBE (120 +/- 43%) sequences displayed lesion
      volumes most efficiently with a trend to overestimation. The Caipirinha DIXON
      (323 +/- 24%) sequence overestimated the volumes significantly during real-time
      monitoring. The volumes measured by MRI with FLASH (61 +/- 30%), Haste (67 +/-
      28%), or radial VIBE (48 +/- 14%) sequences after cooling of the kidney after
      ablation were always underestimated. The Caipirinha DIXON (142 +/- 2%) sequence
      still overestimated the lesion volume after cooling of the kidney. CONCLUSION:
      LITT is a feasible ablation modality in kidney tissue. Moreover, macroscopic and
      MR lesion volume increases time-dependently. For online monitoring, radial VIBE
      and FLASH sequences seem to be most efficient.

PMID- 24902948
TI  - Perturbations in the carbon budget of the tropics.
AB  - The carbon budget of the tropics has been perturbed as a result of human
      influences. Here, we attempt to construct a 'bottom-up' analysis of the
      biological components of the budget as they are affected by human activities.
      There are major uncertainties in the extent and carbon content of different
      vegetation types, the rates of land-use change and forest degradation, but recent
      developments in satellite remote sensing have gone far towards reducing these
      uncertainties. Stocks of carbon as biomass in tropical forests and woodlands add
      up to 271 +/- 16 Pg with an even greater quantity of carbon as soil organic
      matter. Carbon loss from deforestation, degradation, harvesting and peat fires is
      estimated as 2.01 +/- 1.1 Pg annum(-1); while carbon gain from forest and
      woodland growth is 1.85 +/- 0.09 Pg annum(-1). We conclude that tropical lands
      are on average a small carbon source to the atmosphere, a result that is
      consistent with the 'top-down' result from measurements in the atmosphere. If
      they were to be conserved, they would be a substantial carbon sink. Release of
      carbon as carbon dioxide from fossil fuel burning in the tropics is 0.74 Pg
      annum(-1) or 0.57 MgC person(-1) annum(-1) , much lower than the corresponding
      figures from developed regions of the world.

PMID- 24902950
TI  - The speed of sound in silk: linking material performance to biological function.
AB  - Sonic properties of spider silks are measured independent of the web using laser
      vibrometry and ballistic impact providing insights into Nature's design of
      functionalized high-performance materials. Through comparison to cocoon silk and
      other industrial fibers, we find that major ampullate silk has the largest
      wavespeed range of any known material. 

PMID- 24902952
TI  - Human intestinal absorption--neutral molecules and ionic species.
AB  - Analysis of percentage human intestinal absorption (%HIA) for 280 drugs shows
      that an excellent fit can be obtained using only three descriptors for neutral
      molecules with a SD of 13.9%. Use of descriptors for individual cations and
      anions does not lead to any better goodness-of-fit. It is noted that diffusion
      coefficients in water for ionized molecules are almost identical to those for the
      corresponding neutral molecules. Comparison of equation coefficients for HIA with
      those for other processes shows that HIA resembles diffusion in water but does
      not resemble permeation through biological bilayers. It is shown that compound
      substituent effects on HIA are near those for diffusion but are far away from
      substituent effects on permeation through a typical bilayer. Calculations
      indicate that rates of permeation through an unstirred mucosal layer are of the
      same order as experimental rates of permeation in HIA. It is concluded that for
      the 280 compound set, diffusion through the unstirred mucosal layer is the rate
      determining step. The effect on pK(a) in transfer of acids and bases from water
      to another solvent, and of diffusion past a negative charge in a phase/bilayer is
      also considered.

PMID- 24902951
TI  - Development of cyclobutene- and cyclobutane-functionalized fatty acids with
      inhibitory activity against Mycobacterium tuberculosis.
AB  - Eleven fatty acid analogues incorporating four-membered carbocycles
      (cyclobutenes, cyclobutanes, cyclobutanones, and cyclobutanols) were investigated
      for the ability to inhibit the growth of Mycobacterium smegmatis (Msm) and
      Mycobacterium tuberculosis (Mtb). A number of the analogues displayed inhibitory
      activity against both mycobacterial species in minimal media. Several of the
      molecules displayed potent levels of inhibition against Mtb, with MIC values
      equal to or below those observed with the anti-tuberculosis drugs D-cycloserine
      and isoniazid. In contrast, two of the analogues that display the greatest
      activity against Mtb failed to inhibit E. coli growth under either set of
      conditions. Thus, the active molecules identified herein may provide the basis
      for the development of anti-mycobacterial agents against Mtb. 

PMID- 24902954
TI  - Mortality and translocation assay to study the protective capacity of
      Bifidobacterium lactis INL1 against Salmonella Typhimurium infection in mice.
AB  - The mouse has been largely used for the study of the protective capacity of
      probiotics against intestinal infections caused by Salmonella. In this work we
      aimed at comparing the mortality and translocation assay for the study of the
      protective capacity of the human breast milk-derived strain Bifidobacterium
      animalis subsp. lactis INL1 on a model of gut infection by Salmonella enterica
      subsp. enterica serovar Typhimurium. Different doses of S. Typhimurium FUNED and
      B. animalis subsp. lactis INL 1 were administered to Balb/c mice in a mortality
      or a translocation assay. The survival of the control group in the mortality
      assay resulted to be variable along experiments, and then we preferred to use a
      translocation assay where the preventive administration of 109 cfu of
      bifidobacteria/mouse for 10 consecutive days significantly reduced the number of
      infected animals and the levels of translocation to liver and spleen, with
      enhanced secretory immunoglobulin A and interleukin 10 production in the small
      and large intestine, respectively. Ten days of B. animalis subsp. lactis strain
      INL1 administration to mice significantly reduced both the incidence and the
      severity of Salmonella infection in a mouse model of translocation. This work
      provided the first evidence that a translocation assay, compared to a mortality
      assay, could be more useful to study the protective capacity of probiotics
      against Salmonella infection, as more information can be obtained from mice and
      less suffering is conferred to animals due to the fact that the mortality assay
      is shorter than the latter. These facts are in line with the guidelines of animal
      research recently established by the National Centre for the Replacement,
      Refinement & Reduction of Animals in Research. 

PMID- 24902953
TI  - Tooth wear in aging people: an investigation of the prevalence and the
      influential factors of incisal/occlusal tooth wear in northwest China.
AB  - BACKGROUND: The aim of this study was to estimate the prevalence of tooth wear in
      the aging population of northwest China and to investigate the factors associated
      with such tooth wear. METHODS: Cross-sectional analytic clinical and
      questionnaire study was performed in 704 participants who had a mean age of 46.5
      +/- 0.2 SD and of which 367(52.13%) were males and 337(47.87%) female. These
      participants were invited when they attended the hospital which located in
      northwest China for routine oral examination. RESULTS: In the maxilla of the
      examined patients, the rate of tooth wear varied from 85.51% for molar group,
      89.77% for premolar group, 100.0% for canine group to 87.22% for incisor group.
      In the mandible, the rates were 86.36%, 88.92%, 100.0% and 91.19% for the four
      groups respectively. Moreover, both the incisor and canine groups of these
      patients showed median scores of 3, the premolar group showed a median score of
      1, and the molar group had a median score of 2. Additionally, multiple factors
      were considered to contribute to these patterns of tooth wear, especially the
      habitual consumption of a hard or sour diet (P < 0.05,odds ratio 1.21, 95%
      confidence intervals 1.04-1.49). CONCLUSIONS: Tooth wear is a common disease in
      which the anterior teeth exhibit greater wear than posterior teeth. The data
      support an association between tooth wear and dietary patterns.

PMID- 24902955
TI  - Lactobacillus species identification by amplified ribosomal 16S-23S rRNA
      restriction fragment length polymorphism analysis.
AB  - Lactic acid bacteria strains are commonly used for animal and human consumption
      due to their probiotic properties. One of the major genera used is Lactobacillus,
      a highly diverse genus comprised of several closely related species. The
      selection of new strains for probiotic use, especially strains of Lactobacillus,
      is the focus of several research groups. Accurate identification to species level
      is fundamental for research on new strains, as well as for safety assessment and
      quality assurance. The 16S-23S internal transcribed spacer (ITS-1) is a deeply
      homologous region among prokaryotes that is commonly used for identification to
      the species level because it is able to acquire and accumulate mutations without
      compromising general bacterial metabolism. In the present study, 16S-23S ITS
      regions of 45 Lactobacillus species (48 strains) were amplified and subjected to
      independent enzymatic digestions, using 12 restriction enzymes that recognise six
      base sequences. Twenty-nine species showed unique restriction patterns, and could
      therefore be precisely identified solely by this assay (64%). This approach
      proved to be reproducible, allowing us to establish simplified restriction
      patterns for each evaluated species. The restriction patterns of each species
      were similar among homologous strains, and to a large extent reflected
      phylogenetic relationships based on 16S rRNA sequences, demonstrating the
      promising nature of this region for evolutionary studies. 

PMID- 24902956
TI  - Molecular ecological tools to decipher the role of our microbial mass in obesity.
AB  - After birth, our gastrointestinal (GI) tract is colonised by a highly complex
      assemblage of microbes, collectively termed the GI microbiota, that develops
      intimate interactions with our body. Recent evidence indicates that the GI
      microbiota and its products may contribute to the development of obesity and
      related diseases. This, coupled with the current worldwide epidemic of obesity,
      has moved microbiome research into the spotlight of attention. Although the main
      cause of obesity and its associated metabolic complications is excess caloric
      intake compared with expenditure, differences in GI tract microbial ecology
      between individuals might be an important biomarker, mediator or new therapeutic
      target. This can be investigated using a diverse set of complementary so called 
      omics technologies, such as 16S ribosomal RNA gene-targeted composition
      profiling, metabolomics, metagenomics, metatranscriptomics and metaproteomics.
      This review aims to describe the different molecular approaches and their
      contributions to our understanding of the role of the GI microbiota in host
      energy homeostasis. Correspondingly, we highlight their respective strengths, but
      also try to create awareness for their specific limitations. However, it is
      currently still unclear which bacterial groups play a role in the development of
      obesity in humans. This might partly be explained by the heterogeneity in
      genotype, lifestyle, diet and the complex ethology of obesity and its associated
      metabolic disorders (OAMD). Nevertheless, recent research on this matter has
      shown a conceptual shift by focusing on more homogenous subpopulations, through
      the use of both anthropometric (weight, total body fat) as well as biochemical
      variables (insulin resistance, hyperlipidaemia) to define categories. Combined
      with technological advances, recent data suggests that an OAMD associated
      microbiota can be characterised by a potential pro-inflammatory composition, with
      less potential for the production of short chain fatty acids and butyrate in
      particular. 

PMID- 24902957
TI  - Cryptosporidiosis - an occupational risk and a disregarded disease in Estonia.
AB  - BACKGROUND: Cases of cryptosporidiosis have not been officially reported in
      Estonia after the year 2000, and the disease appears to be either under-diagnosed
      or under-reported. FINDINGS: Based on a human case of cryptosporidiosis
      contracted during faecal sampling in dairy farms, cattle considered to be sources
      of infection were analysed for Cryptosporidium spp. by a modified Ziehl Neelsen
      technique and molecular typing. C. parvum subtype IIaA16G1R1 was detected from
      the human case and from calves from one of nine farms enrolled in the study
      providing strong circumstantial evidence of zoonotic transmission from calves to
      humans. CONCLUSION: Cryptosporidiosis presents an occupational risk to people
      with cattle contact, and may also be a risk to the human population in general.
      Thus increased public and medical awareness is warranted.

PMID- 24902958
TI  - The scope for nuclear selection within Termitomyces fungi associated with fungus
      growing termites is limited.
AB  - BACKGROUND: We investigate the scope for selection at the level of nuclei within
      fungal individuals (mycelia) of the mutualistic Termitomyces cultivated by fungus
      growing termites. Whereas in most basidiomycete fungi the number and kind of
      nuclei is strictly regulated to be two per cell, in Termitomyces mycelia the
      number of nuclei per cell is highly variable. We hypothesised that natural
      selection on these fungi not only occurs between mycelia, but also at the level
      of nuclei within the mycelium. We test this hypothesis using in vitro tests with
      five nuclear haplotypes of a Termitomyces species. RESULTS: First, we studied the
      transition from a mixture of five homokaryons (mycelia with identical nuclei)
      each with a different nuclear haplotype to heterokaryons (mycelia with
      genetically different nuclei). In vitro cultivation of this mixture for multiple
      asexual transfers led to the formation of multiple heterokaryotic mycelia, and a
      reduction of mycelial diversity over time. All heterokaryotic mycelia contained
      exactly two types of nucleus. The success of a heterokaryon during in vitro
      cultivation was mainly determined by spore production and to a lesser extent by
      mycelial growth rate. Second, heterokaryons invariably produced more spores than
      homokaryons implying that homokaryons will be outcompeted. Third, no homokaryotic
      'escapes' from a heterokaryon via the formation of homokaryotic spores were
      found, despite extensive spore genotyping. Fourth, in contrast to most studied
      basidiomycete fungi, in Termitomyces sp. no nuclear migration occurs during
      mating, limiting the scope for nuclear competition within the mycelium.
      CONCLUSIONS: Our experiments demonstrate that in this species of Termitomyces the
      scope for selection at the level of the nucleus within an established mycelium is
      limited. Although 'mate choice' of a particular nuclear haplotype is possible
      during mating, we infer that selection primarily occurs between mycelia with two
      types of nucleus (heterokaryons).

PMID- 24902959
TI  - Household health care-seeking costs: experiences from a randomized, controlled
      trial of community-based malaria and pneumonia treatment among under-fives in
      eastern Uganda.
AB  - BACKGROUND: Home and community-based combined treatment of malaria and pneumonia
      has been promoted in Uganda since mid 2011. The combined treatment is justified
      given the considerable overlap between the symptoms of malaria and pneumonia
      among infants. There is limited evidence about the extent to which community
      based care reduces healthcare-seeking costs at the household level in rural and
      urban settings. This paper assesses the rural-urban differences in direct and
      indirect costs of seeking care from formal health facilities compared to
      community medicine distributors (CMDs). METHODS: Exit interviews were conducted
      for 282 (159 rural and 123 urban) caregivers of children below five years who had
      received treatment for fever-related illnesses at selected health centres in
      Iganga and Mayuge districts. Data on the direct and indirect costs incurred while
      seeking care at the health centre visited were obtained. Using another tool,
      household level direct and indirect costs of seeking care from CMDs were
      collected from a total of 470 caregivers (304 rural and 166 urban). Costs
      incurred at health facilities were then compared with costs of seeking care from
      CMDs. RESULTS: Household direct costs of seeking care from health facilities were
      significantly higher for urban-based caregivers than the rural (median cost =
      US$0.42 for urban and zero for rural; p < 0.0001). The same is true for seeking
      care from CMDs (p = 0.0038). Overall, caregivers travelled for an average of 75
      min to reach health centres and spent an average of 80 min at the health centre
      while receiving treatment. However, households in rural areas travelled for a
      significantly longer time (p < 0.001 to reach health care facilities than the
      urban-based caregivers. Besides travelling longer distances, rural caregivers
      spent 150 min seeking care from health facilities compared to 30 min from CMDs.
      CONCLUSION: Time and monetary savings for seeking care from CMDs are
      significantly larger for rural than urban households. Thus, home and community
      based treatment of child febrile illnesses is much more cost-saving for rural
      poor communities, who would spend more time travelling to health facilities -
      which time could be re-directed to productive and income-generating activities.

PMID- 24902961
TI  - Complete pyridine-nucleotide-specific conversion of an NADH-dependent ferredoxin
      reductase.
AB  - The coenzyme specificity of enzymes is one of the critical parameters for the
      engineered production of biological compounds using bacteria. Since NADPH is
      produced abundantly in photosynthetic organisms, conversion of an NADH-specific
      enzyme into an NADPH-specific one is a useful approach for the efficient carbon
      neutral production of biological compounds in photosynthetic organisms. In the
      present study, an NADH-specific ferredoxin reductase component, BphA4 of biphenyl
      dioxygenase BphA from Acidovorax sp. strain KKS102, was changed to an NADPH
      dependent form using a method combining structure-based systematic mutations and
      site-directed random mutagenesis. The resultant CRG mutant, in which Glu175
      Thr176-Gln177 of an NADH-recognition loop in the wild-type BphA4 was replaced
      with Cys175-Arg176-Gly177, was highly specific and active for NADPH, and its
      biochemical and structural properties for NADPH were nearly the same as those of
      the wild-type BphA4 for NADH. In addition, this mutation project was assessed by
      a semi-empirical prediction method of mutation effects, and the results suggested
      that the CRG mutant was one of the best NADPH-specific mutants. 

PMID- 24902960
TI  - Attributable fraction of tobacco smoking on cancer using population-based
      nationwide cancer incidence and mortality data in Korea.
AB  - BACKGROUND: Smoking is by far the most important cause of cancer that can be
      modified at the individual level. Cancer incidence and mortality rates in Korea
      are the highest among all Asian countries, and smoking prevalence in Korean men
      is one of the highest in developed countries. The purpose of the current study
      was to perform a systematic review and provide an evidence-based assessment of
      the burden of tobacco smoking-related cancers in the Korean population. METHODS:
      Sex- and cancer-specific population-attributable fractions (PAF) were estimated
      using the prevalence of ever-smoking and second-hand smoking in 1989 among Korean
      adults, respectively, and the relative risks were estimated from the meta
      analysis of studies performed in the Korean population for ever-smoking and in
      the Asian population for passive smoking. National cancer incidence data from the
      Korea Central Cancer Registry and national cancer mortality data from Statistics
      Korea for the year 2009 were used to estimate the cancer cases and deaths
      attributable to tobacco smoking. RESULTS: Tobacco smoking was responsible for
      20,239 (20.9%) cancer incident cases and 14,377 (32.9%) cancer deaths among adult
      men and 1,930 (2.1%) cancer incident cases and 1,351 (5.2%) cancer deaths among
      adult women in 2009 in Korea. In men, 71% of lung cancer deaths, 55%-72% of upper
      aerodigestive tract (oral cavity, pharynx, esophagus and larynx) cancer deaths,
      23% of liver, 32% of stomach, 27% of pancreas, 7% of kidney and 45% of bladder
      cancer deaths were attributable to tobacco smoking. In women the proportion of
      ever-smoking-attributable lung cancer was 8.1%, while that attributable to second
      hand smoking among non-smoking women was 20.5%. CONCLUSIONS: Approximately one in
      three cancer deaths would be potentially preventable through appropriate control
      of tobacco smoking in Korean men at the population level and individual level.
      For Korean women, more lung cancer cases and deaths were attributable to second
      hand than ever-smoking. Effective control programs against tobacco smoking should
      be further developed and implemented in Korea to reduce the smoking-related
      cancer burden.

PMID- 24902962
TI  - Clinical effects of "pioglitazone", an insulin sensitizing drug, on psoriasis
      vulgaris and its co-morbidities, a double blinded randomized controlled trialx1.
AB  - OBJECTIVES: To evaluate the therapeutic efficacy of pioglitazone on psoriasis
      vulgaris and its comorbidities. MATERIALS AND METHODS: Forty-eight patients with
      moderate-to-severe psoriasis vulgaris were enrolled in this randomized double
      blinded placebo-controlled trial. Active treatment included: oral pioglitazone 30
      mg daily for 10 weeks. Primary outcome (treatment success) was PASI-75. Secondary
      outcomes included changes in metabolic syndrome, insulin resistance and
      cardiovascular risk. RESULTS: Treatment success was achieved in 5/24 (21%) in the
      pioglitazone group compared to 1/24 (4%) in the placebo group; however, this
      difference was not significant (p = 0.081). Compared to placebo, no significant
      difference existed as regards high-sensitive C reactive protein. Metabolic
      syndrome and insulin resistance were not affected. CONCLUSIONS: This short term
      (10 weeks duration) study revealed no effect of pioglitazone 30 mg daily neither
      on the clinical response of moderate-to-severe psoriasis nor on metabolic
      syndrome and insulin resistance. Cardio-protective role appears to be more
      related to improvement of psoriasis. LIMITATION: Short duration of treatment and
      small number of subgroups.

PMID- 24902963
TI  - Low production of reactive oxygen species in granulocytes is associated with
      organ damage in systemic lupus erythematosus.
AB  - INTRODUCTION: Polymorphonuclear leukocytes (PMN) are main effector cells in the
      acute immune response. While the specific role of PMN in systemic lupus
      erythematosus (SLE) and autoimmunity is still unclear, their importance in
      chronic inflammation is gaining more attention. Here we investigate aspects of
      function, bone marrow release and activation of PMN in patients with SLE.
      METHODS: The following PMN functions and subsets were evaluated using flow
      cytometry; (a) production of reactive oxygen species (ROS) after ex vivo
      stimulation with phorbol 12-myristate 13-acetate (PMA) or Escherichia coli (E.
      coli); (b) capacity to phagocytose antibody-coated necrotic cell material; (c)
      PMN recently released from bone marrow, defined as percentage of CD10(-)D16(low)
      in peripheral blood, and (d) PMN activation markers; CD11b, CD62L and C5aR.
      RESULTS: SLE patients (n = 92) showed lower ROS production compared with healthy
      controls (n = 38) after activation ex vivo. The ROS production was not associated
      with corticosteroid dose or other immunotherapies. PMA induced ROS production was
      significantly reduced in patients with severe disease. In contrast, neither ROS
      levels after E. coli activation, nor the capacity to phagocytose were associated
      with disease severity. This suggests that decreased ROS production after PMA
      activation is a sign of changed PMN behaviour rather than generally impaired
      functions. The CD10(-)CD16(low) phenotype constitute 2% of PMN in peripheral
      blood of SLE patients compared with 6.4% in controls, indicating a decreased
      release of PMN from the bone marrow in SLE. A decreased expression of C5aR on PMN
      was observed in SLE patients, pointing towards in vivo activation. CONCLUSIONS:
      Our results indicate that PMN from SLE patients have altered function, are partly
      activated and are released abnormally from bone marrow. The association between
      low ROS formation in PMN and disease severity is consistent with findings in
      other autoimmune diseases and might be considered as a risk factor.

PMID- 24902964
TI  - Return to play management after concussion in football: recommendations for team
      physicians.
AB  - A concussion is a rare but potentially serious injury of football players. Thus,
      an immediate and valid diagnosis, estimate of severity and therapeutic management
      is required. To summarise the published information on management of concussion
      with respect to a safe return to play (RTP), a literature search was conducted.
      Current guidelines on concussion in sports and significant studies on concussion
      in football were analysed. After concussion, management and RTP decision should
      remain in the area of clinical judgement on an individualised basis according to
      the current international guidelines. If a concussion is suspected, the player
      should not be allowed to RTP the same day. The RTP programme should follow a
      gradual step-wise procedure. A concussed player should not RTP unless he/she is
      asymptomatic and the neurological and neuropsychological examinations are normal.
      Untimely RTP bears an increased risk of sustaining another more severe brain
      injury and repetitive brain injury of long-term sequelae. In football, the
      management of concussion should primarily follow the recommendations proposed by
      the Concussion in Sports Group. Information and education of players and their
      medical and coaching team help to protect the players' health. Future studies on
      concussion should include validated and detailed information on RTP protocols.

PMID- 24902965
TI  - MODFLOW-Based Coupled Surface Water Routing and Groundwater-Flow Simulation.
AB  - In this paper, we present a flexible approach for simulating one- and two
      dimensional routing of surface water using a numerical surface water routing
      (SWR) code implicitly coupled to the groundwater-flow process in MODFLOW. Surface
      water routing in SWR can be simulated using a diffusive-wave approximation of the
      Saint-Venant equations and/or a simplified level-pool approach. SWR can account
      for surface water flow controlled by backwater conditions caused by small water
      surface gradients or surface water control structures. A number of typical
      surface water control structures, such as culverts, weirs, and gates, can be
      represented, and it is possible to implement operational rules to manage surface
      water stages and streamflow. The nonlinear system of surface water flow equations
      formulated in SWR is solved by using Newton methods and direct or iterative
      solvers. SWR was tested by simulating the (1) Lal axisymmetric overland flow, (2)
      V-catchment, and (3) modified Pinder-Sauer problems. Simulated results for these
      problems compare well with other published results and indicate that SWR provides
      accurate results for surface water-only and coupled surface water/groundwater
      problems. Results for an application of SWR and MODFLOW to the Snapper Creek area
      of Miami-Dade County, Florida, USA are also presented and demonstrate the value
      of coupled surface water and groundwater simulation in managed, low-relief
      coastal settings. 

PMID- 24902966
TI  - Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression.
AB  - BACKGROUND AND PURPOSE: Doxorubicin-based chemotherapy induces cardiotoxicity,
      which limits its clinical application. We previously reported the protective
      effects of quercetin against doxorubicin-induced hepatotoxicity. In this study,
      we tested the effects of quercetin on the expression of Bmi-1, a protein
      regulating mitochondrial function and ROS generation, as a mechanism underlying
      quercetin-mediated protection against doxorubicin-induced cardiotoxicity.
      EXPERIMENTAL APPROACH: Effects of quercetin on doxorubicin-induced cardiotoxicity
      was evaluated using H9c2 cardiomyocytes and C57BL/6 mice. Changes in apoptosis,
      mitochondrial function, oxidative stress and related signalling were evaluated in
      H9c2 cells. Cardiac function, serum enzyme activity and reactive oxygen species
      (ROS) generation were measured in mice after a single injection of doxorubicin
      with or without quercetin pre-treatment. KEY RESULTS: In H9c2 cells, quercetin
      reduced doxorubicin-induced apoptosis, mitochondrial dysfunction, ROS generation
      and DNA double-strand breaks. The quercetin-mediated protection against
      doxorubicin toxicity was characterized by decreased expression of Bid, p53 and
      oxidase (p47 and Nox1) and by increased expression of Bcl-2 and Bmi-1. Bmi-1
      siRNA abolished the protective effect of quercetin against doxorubicin-induced
      toxicity in H9c2 cells. Furthermore, quercetin protected mice from doxorubicin
      induced cardiac dysfunction that was accompanied by reduced ROS levels and lipid
      peroxidation, but enhanced the expression of Bmi-1 and anti-oxidative superoxide
      dismutase. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that quercetin
      decreased doxorubicin-induced cardiotoxicity in vitro and in vivo by reducing
      oxidative stress by up-regulation of Bmi-1 expression. The findings presented in
      this study have potential applications in preventing doxorubicin-induced
      cardiomyopathy.

PMID- 24902968
TI  - Multiple perianal papular lesions in a 37-year-old woman.

PMID- 24902967
TI  - A systematic review of the epidemiology of hepatitis E virus in Africa.
AB  - BACKGROUND: Hepatitis E Virus (HEV) infection is a newly recognized serious
      threat to global public health and Africa is suspected to be among the most
      severely affected regions in the world. Understanding HEV epidemiology in Africa
      will expedite the implementation of evidence-based control policies aimed at
      preventing the spread of HEV including policies for the use of available
      resources such as HEV vaccines. METHODS: Here we present a comprehensive review
      of HEV epidemiology in Africa based on published data. We searched for articles
      on HEV epidemiology in Africa from online databases such as PubMed, Scopus, and
      ISI Web of Science and critically reviewed appropriate publications to extract
      consistent findings, identify knowledge gaps, and suggest future studies.
      RESULTS: Taking a particularly high toll in pregnant women and their fetuses, HEV
      has infected human populations in 28 of 56 African countries. Since 1979, 17 HEV
      outbreaks have been reported about once every other year from Africa causing a
      reported 35,300 cases with 650 deaths. CONCLUSIONS: In Africa, HEV infection is
      not new, is widespread, and the number of reported outbreaks are likely a
      significant underestimate. The authors suggest that this is a continent-wide
      public health problem that deserves the attention of local, regional and
      international agencies to implement control policies that can save numerous
      lives, especially those of pregnant women and their fetuses.

PMID- 24902969
TI  - Evaluation of candidate spermatogonial markers ID4 and GPR125 in testes of adult
      human cadaveric organ donors.
AB  - The optimal markers for human spermatogonial stem cells (SSCs) are not known.
      Among the genes recently linked to SSCs in mice and other animals are the basic
      helix-loop-helix transcription factor ID4 and the orphan G-protein-coupled
      receptor GPR125. While ID4 and GPR125 are considered putative markers for SSCs,
      they have not been evaluated for coexpression in human tissue. Furthermore,
      neither the size nor the character of the human spermatogonial populations that
      express ID4 and GPR125, respectively, are known. A major barrier to addressing
      these questions is the availability of healthy adult testis tissue from donors
      with no known reproductive health problems. To overcome this obstacle, we have
      employed healthy testicular tissue from a novel set of organ donors (n = 16; aged
      17-68 years) who were undergoing post-mortem clinical organ procurement. Using
      immunolabelling, we found that ID4 and GPR125 are expressed on partially
      overlapping spermatogonial populations and are more broadly expressed in the
      normal adult human testis. In addition, we found that expression of ID4 remained
      stable during ageing. These findings suggest that ID4 and GPR125 could be
      efficacious for identifying previously unrecognized human spermatogonial
      subpopulations in conjunction with other putative human stem cell markers, both
      in younger and older donors.

PMID- 24902970
TI  - Mechanisms of plaque formation and rupture.
AB  - Atherosclerosis causes clinical disease through luminal narrowing or by
      precipitating thrombi that obstruct blood flow to the heart (coronary heart
      disease), brain (ischemic stroke), or lower extremities (peripheral vascular
      disease). The most common of these manifestations is coronary heart disease,
      including stable angina pectoris and the acute coronary syndromes.
      Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at
      specific sites of the arterial tree through intimal inflammation, necrosis,
      fibrosis, and calcification. After decades of indolent progression, such plaques
      may suddenly cause life-threatening coronary thrombosis presenting as an acute
      coronary syndrome. Most often, the culprit morphology is plaque rupture with
      exposure of highly thrombogenic, red cell-rich necrotic core material. The
      permissive structural requirement for this to occur is an extremely thin fibrous
      cap, and thus, ruptures occur mainly among lesions defined as thin-cap
      fibroatheromas. Also common are thrombi forming on lesions without rupture
      (plaque erosion), most often on pathological intimal thickening or
      fibroatheromas. However, the mechanisms involved in plaque erosion remain largely
      unknown, although coronary spasm is suspected. The calcified nodule has been
      suggested as a rare cause of coronary thrombosis in highly calcified and tortious
      arteries in older individuals. To characterize the severity and prognosis of
      plaques, several terms are used. Plaque burden denotes the extent of disease,
      whereas plaque activity is an ambiguous term, which may refer to one of several
      processes that characterize progression. Plaque vulnerability describes the short
      term risk of precipitating symptomatic thrombosis. In this review, we discuss
      mechanisms of atherosclerotic plaque initiation and progression; how plaques
      suddenly precipitate life-threatening thrombi; and the concepts of plaque burden,
      activity, and vulnerability. 

PMID- 24902973
TI  - Genetics of coronary artery disease.
AB  - There is almost no data on the genetics of acute coronary syndromes, so this
      review discusses primarily the 50 genetic risk variants associated with coronary
      artery disease that are of genome-wide significance in the discovery population
      and replicated in an independent population. All of these risk variants are
      extremely common with more than half occurring in >50% of the general population.
      They increased only minimally the relative risk for coronary artery disease. The
      most striking finding is that 35 of the 50 risk variants act independently of
      known risk factors, indicating there are several pathways yet to be appreciated,
      contributing to the pathogenesis of coronary atherosclerosis and myocardial
      infarction. All of the genetic variants seem to act through atherosclerosis,
      except for the ABO blood groups, which show that A and B are associated with
      increased risk for myocardial infarction, mediated by a prolonged von Willebrand
      plasma half life leading to thrombosis. The potential molecular mechanisms of
      9p21 are discussed, including cell cycle kinase inhibitors. Discovery of risk
      variants associated with PCSK9 has led to the development of novel treatment for
      plasma low-density lipoprotein cholesterol. A monoclonal antibody inhibiting
      PCSK9 has already undergone phase I and II clinical trials, showing it is a
      potent inhibitor of low-density lipoprotein cholesterol and is mediated through
      more rapid removal of low-density lipoprotein cholesterol from the plasma. This
      therapy complements that of statin therapy, which inhibits the synthesis of
      cholesterol. The benefits of Mendelian randomization to assess safety and
      efficacy and their limitations are discussed along with future directions. 

PMID- 24902972
TI  - Lipoproteins as biomarkers and therapeutic targets in the setting of acute
      coronary syndrome.
AB  - The period following an acute coronary syndrome (ACS) represents a critical time
      frame with a high risk for recurrent events and death. The pathogenesis of this
      increase in clinical cardiovascular disease events after ACS is complex, with
      molecular mechanisms including increased thrombosis and inflammation.
      Dyslipoproteinemia is common in patients with ACS and predictive of recurrent
      cardiovascular disease events after presentation with an ACS event. Although
      randomized clinical trials have provided fairly convincing evidence that high
      dose statins reduce the risk of recurrent cardiovascular events after ACS, there
      remain questions about how aggressively to reduce low-density lipoprotein
      cholesterol levels in ACS. Furthermore, no other lipid-related interventions have
      yet been proven to be effective in reducing major cardiovascular events after
      ACS. Here, we review the relationship of lipoproteins as biomarkers to
      cardiovascular risk after ACS, the evidence for lipid-targeted interventions, and
      the potential for novel therapeutic approaches in this arena. 

PMID- 24902975
TI  - Reperfusion strategies in acute coronary syndromes.
AB  - The appropriate timing of angiography to facilitate revascularization is
      essential to optimize outcomes in patents with ST-segment-elevation myocardial
      infarction and non-ST-segment-elevation acute coronary syndromes. Timely
      reperfusion of the infarct-related coronary artery in ST-segment-elevation
      myocardial infarction both with fibrinolysis or percutaneous coronary
      intervention minimizes myocardial damage, reduces infarct size, and decreases
      morbidity and mortality. Primary percutaneous coronary intervention is the
      preferred reperfusion method if it can be performed in a timely manner.
      Strategies to reduce health system-related delays in reperfusion include
      regionalization of ST-segment-elevation myocardial infarction care, performing
      prehospital ECGs, prehospital activation of the catheterization laboratory,
      bypassing geographically closer nonpercutaneous coronary intervention-capable
      hospitals, bypassing the percutaneous coronary intervention-capable hospital
      emergency department, and early and consistent availability of the
      catheterization laboratory team. With implementation of such strategies, there
      has been significant improvement in process measures, including door-to-balloon
      time. However, despite reductions in door-to-balloon times, there has been little
      change during the past several years in in-hospital mortality, suggesting
      additional factors including patient-related delays, optimization of tissue-level
      perfusion, and cardioprotection must be addressed to improve patient outcomes
      further. Early angiography followed by revascularization when appropriate also
      reduces rates of death, MI, and recurrent ischemia in patients with non-ST
      segment-elevation acute coronary syndromes, with the greatest benefits realized
      in the highest risk patients. Among patients with non-ST-segment-elevation acute
      coronary syndromes with multivessel disease, choice of revascularization modality
      should be made as in stable coronary artery disease, with a goal of complete
      ischemic revascularization. 

PMID- 24902971
TI  - Inflammation and its resolution as determinants of acute coronary syndromes.
AB  - Inflammation contributes to many of the characteristics of plaques implicated in
      the pathogenesis of acute coronary syndromes. Moreover, inflammatory pathways not
      only regulate the properties of plaques that precipitate acute coronary syndromes
      but also modulate the clinical consequences of the thrombotic complications of
      atherosclerosis. This synthesis will provide an update on the fundamental
      mechanisms of inflammatory responses that govern acute coronary syndromes and
      also highlight the ongoing balance between proinflammatory mechanisms and
      endogenous pathways that can promote the resolution of inflammation. An
      appreciation of the countervailing mechanisms that modulate inflammation in
      relation to acute coronary syndromes enriches our fundamental understanding of
      the pathophysiology of this important manifestation of atherosclerosis. In
      addition, these insights provide glimpses into potential novel therapeutic
      interventions to forestall this ultimate complication of the disease. 

PMID- 24902976
TI  - Antiplatelet and anticoagulation therapy for acute coronary syndromes.
AB  - The past 2 decades have witnessed the introduction and demise of several
      different antithrombotic medications for acute coronary syndromes. Part of the
      assessment of these compounds has been their effect on thrombotic events relative
      to the degree of increase in bleeding events. This review will outline the data
      supporting various antiplatelet and anticoagulant therapies and their
      combinations in patients with acute coronary syndromes and related disorders in
      both the acute and chronic phases of therapy. 

PMID- 24902974
TI  - Imaging plaques to predict and better manage patients with acute coronary events.
AB  - Culprit lesions of patients, who have had an acute coronary syndrome commonly,
      are ruptured coronary plaques with superimposed thrombus. The precursor of such
      lesions is an inflamed thin-capped fibroatheroma. These plaques can be imaged by
      means of invasive techniques, such as intravascular ultrasound (and derived
      techniques), optical coherence tomography, and near-infrared spectroscopy. Often
      these patients exhibit similar (multiple) plaques beyond the culprit lesion.
      These remote plaques can be assessed noninvasively by computed tomographic
      angiography and MRI and also using invasive imaging. The detection of these
      remote plaques is not only feasible but also in natural history studies have been
      associated with clinical coronary events. Different systemic pharmacological
      treatments have been studied (mostly statins) with modest success and, therefore,
      newer approaches are being tested. Local treatment for such lesions is in its
      infancy and larger, prospective, and randomized trials are needed. This review
      will describe the pathological and imaging findings in culprit lesions of
      patients with acute coronary syndrome and the assessment of remote plaques. In
      addition, the pharmacological and local treatment options will be reviewed. 

PMID- 24902977
TI  - Nonantithrombotic medical options in acute coronary syndromes: old agents and new
      lines on the horizon.
AB  - Acute coronary syndromes (ACS) constitute a spectrum of clinical presentations
      ranging from unstable angina and non-ST-segment elevation myocardial infarction
      to ST-segment myocardial infarction. Myocardial ischemia in this context occurs
      as a result of an abrupt decrease in coronary blood flow and resultant imbalance
      in the myocardial oxygen supply-demand relationship. Coronary blood flow is
      further compromised by other mechanisms that increase coronary vascular
      resistance or reduce coronary driving pressure. The goals of treatment are to
      decrease myocardial oxygen demand, increase coronary blood flow and oxygen
      supply, and limit myocardial injury. Treatments are generally divided into
      disease-modifying agents or interventions that improve hard clinical outcomes and
      other strategies that can reduce ischemia. In addition to traditional drugs such
      as beta-blockers and inhibitors of the renin-angiotensin-aldosterone system,
      newer agents have expanded the number of molecular pathways targeted for
      treatment of ACS. Ranolazine, trimetazidine, nicorandil, and ivabradine are
      medications that have been shown to reduce myocardial ischemia through diverse
      mechanisms and have been tested in limited fashion in patients with ACS.
      Attenuating the no-reflow phenomenon and reducing the injury compounded by acute
      reperfusion after a period of coronary occlusion are active areas of research.
      Additionally, interventions aimed at ischemic pre- and postconditioning may be
      useful means by which to limit myocardial infarct size. Trials are also underway
      to examine altered metabolic and oxygen-related pathways in ACS. This review will
      discuss traditional and newer anti-ischemic therapies for patients with ACS,
      exclusive of revascularization, antithrombotic agents, and the use of high
      intensity statins. 

PMID- 24902979
TI  - A nanoscale secondary ion mass spectrometry study of dinoflagellate functional
      diversity in reef-building corals.
AB  - Nutritional interactions between corals and symbiotic dinoflagellate algae lie at
      the heart of the structural foundation of coral reefs. Whilst the genetic
      diversity of Symbiodinium has attracted particular interest because of its
      contribution to the sensitivity of corals to environmental changes and bleaching
      (i.e. disruption of coral-dinoflagellate symbiosis), very little is known about
      the in hospite metabolic capabilities of different Symbiodinium types. Using a
      combination of stable isotopic labelling and nanoscale secondary ion mass
      spectrometry (NanoSIMS), we investigated the ability of the intact symbiosis
      between the reef-building coral Isopora palifera, and Symbiodinium C or D types,
      to assimilate dissolved inorganic carbon (via photosynthesis) and nitrogen (as
      ammonium). Our results indicate that Symbiodinium types from two clades naturally
      associated with I. palifera possess different metabolic capabilities. The
      Symbiodinium C type fixed and passed significantly more carbon and nitrogen to
      its coral host than the D type. This study provides further insights into the
      metabolic plasticity among different Symbiodinium types in hospite and
      strengthens the evidence that the more temperature-tolerant Symbiodinium D type
      may be less metabolically beneficial for its coral host under non-stressful
      conditions.

PMID- 24902980
TI  - Roothairless5, which functions in maize (Zea mays L.) root hair initiation and
      elongation encodes a monocot-specific NADPH oxidase.
AB  - Root hairs are instrumental for nutrient uptake in monocot cereals. The maize
      (Zea mays L.) roothairless5 (rth5) mutant displays defects in root hair
      initiation and elongation manifested by a reduced density and length of root
      hairs. Map-based cloning revealed that the rth5 gene encodes a monocot-specific
      NADPH oxidase. RNA-Seq, in situ hybridization and qRT-PCR experiments
      demonstrated that the rth5 gene displays preferential expression in root hairs
      but also accumulates to low levels in other tissues. Immunolocalization detected
      RTH5 proteins in the epidermis of the elongation and differentiation zone of
      primary roots. Because superoxide and hydrogen peroxide levels are reduced in the
      tips of growing rth5 mutant root hairs as compared with wild-type, and Reactive
      oxygen species (ROS) is known to be involved in tip growth, we hypothesize that
      the RTH5 protein is responsible for establishing the high levels of ROS in the
      tips of growing root hairs required for elongation. Consistent with this
      hypothesis, a comparative RNA-Seq analysis of 6-day-old rth5 versus wild-type
      primary roots revealed significant over-representation of only two gene ontology
      (GO) classes related to the biological functions (i.e. oxidation/reduction and
      carbohydrate metabolism) among 893 differentially expressed genes (FDR <5%).
      Within these two classes the subgroups 'response to oxidative stress' and
      'cellulose biosynthesis' were most prominently represented. 

PMID- 24902978
TI  - Global perspective on acute coronary syndrome: a burden on the young and poor.
AB  - Ischemic heart disease (IHD) is the greatest single cause of mortality and loss
      of disability-adjusted life years worldwide, and a substantial portion of this
      burden falls on low- and middle-income countries (LMICs). Deaths from IHD and
      acute coronary syndrome (ACS) occur, on average, at younger ages in LMICs than in
      high-income countries, often at economically productive ages, and likewise
      frequently affect the poor within LMICs. Although data about ACS in LMICs are
      limited, there is a growing literature in this area and the research gaps are
      being steadily filled. In high-income countries, decades of investigation into
      the risk factors for ACS and development of behavioral programs, medications,
      interventional procedures, and guidelines have provided us with the tools to
      prevent and treat events. Although similar tools can be, and in fact have been,
      implemented in many LMICs, challenges remain in the development and
      implementation of cardiovascular health promotion activities across the entire
      life course, as well as in access to treatment for ACS and IHD. Intersectoral
      policy initiatives and global coordination are critical elements of ACS and IHD
      control strategies. Addressing the hurdles and scaling successful health
      promotion, clinical and policy efforts in LMICs are necessary to adequately
      address the global burden of ACS and IHD.

PMID- 24902981
TI  - Transvenous stimulation of the renal sympathetic nerves increases systemic blood
      pressure: a potential new treatment option for neurocardiogenic syncope.
AB  - BACKGROUND: Neurocardiogenic syncope (NCS) is a common and sometimes debilitating
      disorder, with no consistently effective treatment. NCS is due to a combination
      of bradycardia and vasodilation leading to syncope. Although pacemaker devices
      have been tried in treating the bradycardic aspect of NCS, no device-based
      therapy exists to treat the coexistent vasodilation that occurs. The renal
      sympathetic innervation has been the target of denervation to treat hypertension.
      We hypothesized that stimulation of the renal sympathetic nerves can increase
      blood pressure and counteract vasodilation in NCS. METHODS AND RESULTS: High
      frequency stimulation (800-900 pps, 10 V, 30-200 seconds) was performed using a
      quadripolar catheter in the renal vein of 7 dogs and 1 baboon. A significant
      increase in blood pressure (BP; mean [SD] systolic BP 117 [+/-28] vs. 128 [+/
      33], diastolic BP 75 [+/-19] vs. 87 [+/-29] mmHg) was noted during the
      stimulation, which returned to baseline after cessation of stimulation. The mean
      increase in systolic and diastolic BP was 13.0 (+/-3.3) (P = 0.006) and 10.2 (+/
      4.6) (P = 0.08), respectively. CONCLUSION: We report the first ever study of
      feasibility and safety of high-frequency electrical stimulation of the renal
      sympathetic innervation to increase BP in animal models. This has potential
      applications in the treatment of hypotensive states such as NCS.

PMID- 24902982
TI  - Determination of optimal vitamin D3 dosing regimens in HIV-infected paediatric
      patients using a population pharmacokinetic approach.
AB  - AIMS: To investigate 25-hydroxycholecalciferol [25(OH)D] population
      pharmacokinetics in children and adolescents, to establish factors that influence
      25(OH)D pharmacokinetics and to assess different vitamin D3 dosing schemes to
      reach sufficient 25(OH)D concentrations (>30 ng ml(-1) ). METHODS: This
      monocentric prospective study included 91 young HIV-infected patients aged 3 to
      24 years. Patients received a 100 000 IU vitamin D3 supplementation. A total of
      171 25(OH)D concentrations were used to perform a population pharmacokinetic
      analysis. RESULTS: At baseline 28% of patients had 25(OH)D concentrations below
      10 ng ml(-1) , 69% between 10 and 30 ng ml(-1) and 3% above 30 ng ml(-1) .
      25(OH)D pharmacokinetics were best described by a one compartment model with an
      additional production parameter reflecting the input from diet and sun exposure.
      The effects of skin phototype and bodyweight were significant on 25(OH)D
      production before any supplementation. The basal level was 27% lower in non-white
      skin phototype patients and was slightly decreased with bodyweight. No
      significant differences in 25(OH)D concentrations were related to antiretroviral
      drugs. To obtain concentrations between 30 and 80 ng ml(-1) , patients with
      baseline concentrations between 10 and 30 ng ml(-1) should receive 100 000 IU per
      3 months. However, vitamin D deficient patients (<10 ng ml(-1) ) would need an
      intensive phase of 100 000 IU per 2 weeks (two times) followed 2 weeks later by a
      maintenance phase of 100 000 IU per 3 months. CONCLUSIONS: Skin phototype and
      bodyweight had an influence on the basal production of 25(OH)D. According to
      25(OH)D baseline concentrations, dosing schemes to reach sufficient
      concentrations are proposed.

PMID- 24902983
TI  - Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized
      phase III study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of USL255, Qudexy(TM) XR
      (topiramate) extended-release capsules, as an adjunctive treatment for refractory
      partial-onset seizures (POS) in adults taking one to three concomitant
      antiepileptic drugs. METHODS: In this global phase III study (PREVAIL;
      NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200
      mg/day) or placebo. The primary and key secondary efficacy endpoints were median
      percent reduction in weekly POS frequency and responder rate (proportion of
      patients with >= 50% reduction in seizure frequency). Seizure freedom was also
      assessed. Safety (adverse events, clinical and laboratory findings), as well as
      treatment effects on quality of life (QOLIE-31-P) and clinical global impression
      of change (CGI-C), were evaluated. RESULTS: Across the entire 11-week treatment
      phase, USL255 significantly reduced the median percent seizure frequency and
      significantly improved responder rate compared with placebo. Efficacy over
      placebo was observed early in treatment, in patients with highly refractory POS,
      and in those with the most debilitating seizure types (i.e., complex partial,
      partial secondarily generalized). USL255 was safe and generally well tolerated
      with a low incidence of neurocognitive adverse events. USL255 was associated with
      significant clinical improvement without adversely affecting quality of life.
      SIGNIFICANCE: The PREVAIL phase III clinical study demonstrated that once-daily
      USL255 (200 mg/day) significantly improved seizure control and was safe and
      generally well tolerated with few neurocognitive side effects.

PMID- 24902985
TI  - Authors' reply to Balzer and colleagues.

PMID- 24902984
TI  - Improving patients' understanding of terms and phrases commonly used in self
      reported measures of sexual function.
AB  - INTRODUCTION: There is a significant gap in research regarding the readability
      and comprehension of existing sexual function measures. Patient-reported outcome
      measures may use terms not well understood by respondents with low literacy. AIM:
      This study aims to test comprehension of words and phrases typically used in
      sexual function measures to improve validity for all individuals, including those
      with low literacy. METHODS: We recruited 20 men and 28 women for cognitive
      interviews on version 2.0 of the Patient-Reported Outcome Measurement Information
      System((r)) (PROMIS((r)) ) Sexual Function and Satisfaction measures. We assessed
      participants' reading level using the word reading subtest of the Wide Range
      Achievement Test. Sixteen participants were classified as having low literacy.
      MAIN OUTCOME MEASURES: In the first round of cognitive interviews, each survey
      item was reviewed by five or more people, at least two of whom had lower than a
      ninth-grade reading level (low literacy). Patient feedback was incorporated into
      a revised version of the items. In the second round of interviews, an additional
      three or more people (at least one with low literacy) reviewed each revised item.
      RESULTS: Participants with low literacy had difficulty comprehending terms such
      as aroused, orgasm, erection, ejaculation, incontinence, and vaginal penetration.
      Women across a range of literacy levels had difficulty with clinical terms like
      labia and clitoris. We modified unclear terms to include parenthetical
      descriptors or slang equivalents, which generally improved comprehension.
      CONCLUSIONS: Common words and phrases used across measures of self-reported
      sexual function are not universally understood. Researchers should appreciate
      these misunderstandings as a potential source of error in studies using self
      reported measures of sexual function. This study also provides evidence for the
      importance of including individuals with low literacy in cognitive pretesting
      during the measure development.

PMID- 24902986
TI  - Storage in ultra-low-temperature decreases the levels of IgM anticardiolipin
      antibody in serum samples from tuberculosis patients.
AB  - The evaluation of novel tuberculosis (TB) biomarkers relies on analysis of
      previously stored sample sets. We aimed to determine the effect of storage
      temperature on serum IgM anticardiolipin antibody levels in samples from TB
      patients. Ultra-low-temperature storage decreased IgM anticardiolipin levels. We
      recommend against using ultra-low-temperature storage when investigating IgM
      anticardiolipin biomarker-based tests.

PMID- 24902987
TI  - Possible patterns of epidermal melanocyte disappearance in nonsegmental vitiligo:
      a clinicopathological study.
AB  - BACKGROUND: The depigmentation of vitiligo results in a progressive and chronic
      melanocyte loss with rare melanocytes occasionally remaining in the epidermis or
      the hair follicle reservoirs. Destruction by immune infiltrates in close contact
      with melanocytes within microvesicles and/or detachment of melanocytes followed
      by their transepidermal elimination should be regarded as possible mechanisms of
      chronic loss of pigment cells. OBJECTIVES: To assess the frequency of these two
      histological findings and to establish a direct correlation with clinical
      features. METHODS: This was a prospective observational study that took place
      over 1 year. Each patient received a standardized evaluation that included
      daylight and Wood's lamp examinations, pictures, biopsies performed on the
      marginal area, and histological and immunohistological studies. A second
      examination to assess the activity of the lesions was performed 1 year after
      inclusion in the study. Clinical changes associated with microvesicles were
      compared with those associated with detached melanocytes from the basal layer.
      RESULTS: This study included 50 patients. The histological findings were
      classified as inflammatory with isolated microvesicles (29 cases),
      noninflammatory with only detached melanocytes from the basal layer (12 cases)
      and a combination of coexisting microvesicles and detached melanocytes (six
      cases). Correlations were obtained between the histological findings and clinical
      features (aspect and activity of the lesions) and E-cadherin expression.
      CONCLUSIONS: Our data suggest the existence of two patterns of melanocyte
      disappearance in nonsegmental vitiligo.

PMID- 24902988
TI  - Suture-free technique for canine ureteral resection-anastomosis using a
      microvascular anastomotic system: a cadaveric study.
AB  - OBJECTIVE: To describe a suture-free technique for canine ureteral resection
      anastomosis using a microvascular anastomotic system (MAS) and to compare
      surgical time and burst pressure of hand-sewn (HS) ureteral end-to-end
      anastomosis with the MAS technique. STUDY DESIGN: Experimental ex vivo study.
      ANIMALS: Canine cadavers (n = 8). METHODS: For each cadaver, 1 ureter was
      randomly assigned to undergo HS anastomosis and the contralateral ureter had MAS
      anastomosis. The first 3 cadavers (6 ureters) were used to refine the MAS
      technique. In the other 5 dogs, surgical time and ureteral burst pressure were
      compared between groups (n = 5 ureters/group). RESULTS: Preliminary procedures
      showed that selective impaling of the mucosa and submucosa (without muscularis
      and adventitia) is necessary to allow complete mechanical interlock of the
      anastomotic rings for the MAS technique. Median anastomotic time was
      significantly shorter for MAS (7.6 min) than HS (16.6 min; p = .029) and burst
      pressure higher for MAS (393 cm H2 O) than HS (180 cm H2 O; p = .012).
      CONCLUSION: This study demonstrated the feasibility of a suture-free technique of
      canine ureteral resection-anastomosis using a commercially available MAS. The MAS
      anastomosis was faster and had higher burst strength compared with the HS
      anastomosis.

PMID- 24902989
TI  - DSM-5-defined 'mixed features' and Benazzi's mixed depression: which is
      practically useful to discriminate bipolar disorder from unipolar depression in
      patients with depression?
AB  - AIMS: Irritability, psychomotor agitation, and distractibility in a major
      depressive episode (MDE) should not be counted as manic/hypomanic symptoms of DSM
      5-defined mixed features; however, this remains controversial. The practical
      usefulness of this definition in discriminating bipolar disorder (BP) from major
      depressive disorder (MDD) in patients with depression was compared with that of
      Benazzi's mixed depression, which includes these symptoms. METHODS: The
      prevalence of both definitions of mixed depression in 217 patients with MDE (57
      bipolar II disorder, 35 BP not otherwise specified, and 125 MDD cases), and their
      operating characteristics regarding BP diagnosis were compared. RESULTS: The
      prevalence of both Benazzi's mixed depression and DSM-5-defined mixed features
      was significantly higher in patients with BP than it was in patients with MDD,
      with the latter being quite low (62.0% vs 12.8% [P < 0.0001], and 7.6% vs 0% [P <
      0.0021], respectively). The area under the receiver operating curve for BP
      diagnosis according to the number of all manic/hypomanic symptoms was numerically
      larger than that according to the number of manic/hypomanic symptoms excluding
      the above-mentioned three symptoms (0.798; 95% confidence interval, 0.736-0.859
      vs 0.722; 95% confidence interval, 0.654-0.790). The sensitivity/specificity of
      DSM-5-defined mixed features and Benazzi's mixed depression for BP diagnosis were
      5.1%/100% and 55.1%/87.2%, respectively. CONCLUSIONS: DSM-5-defined mixed
      features were too restrictive to discriminate BP from MDD in patients with
      depression compared with Benazzi's definition. To confirm this finding, studies
      that include patients with BP-I and using tools to assess manic/hypomanic
      symptoms during MDE are necessary.

PMID- 24902990
TI  - Vascular access vulnerability in intensive hemodialysis: a significant Achilles'
      heel?
AB  - BACKGROUND: Frequent hemodialysis (HD) may be associated with an increased risk
      of vascular access complications. Studies addressing vascular access outcomes in
      frequent HD show conflicting results. METHODS: We searched Medline for trials
      looking at vascular access outcomes in frequent HD. RESULTS: Nineteen studies met
      the inclusion criteria; only studies with a control group were included for
      analysis (n = 15). The vascular access event rate was higher in intensive HD as
      compared to conventional HD (difference of 6.7 events per 100 patient-years, p =
      0.009). Overall event rates were not significantly different between conventional
      and intensive HD when stratified for access type, but were notably higher in the
      arteriovenous grafts and catheter group as compared to the arteriovenous fistula
      (AVF) group. CONCLUSION: Intensive HD is associated with an increased risk of
      vascular access complications. Overall reported event rates were lower in the AVF
      group. Further controlled studies should investigate whether a 'fistula first'
      strategy may be recommended also for intensive HD.

PMID- 24902991
TI  - Muscle echo intensity: reliability and conditioning factors.
AB  - OBJECTIVE: To assess the issue of muscle echo intensity reliability and to
      investigate the relationship between muscle echo intensity and size, shape and
      location of the region of interest (ROI) used for echo intensity quantification.
      METHODS: Ultrasonographic scans of the following five muscles were acquired in
      twenty healthy subjects: biceps brachii, rectus femoris, vastus lateralis,
      tibialis anterior and medial gastrocnemius. Muscle echo intensity was quantified
      in each scan. RESULTS: We found that the agreement between the different sized
      ROIs considered in each scan ranged from moderate (ICC: 0.54) to high (ICC: 0.86)
      and that the echo intensity consistency between equal sized ROIs of the three
      scans ranged from low (ICC: 0.42) to very high (0.91). The echo intensity of
      tibialis anterior and rectus femoris was different between different sized,
      shaped and located ROIs. The echo intensity of biceps brachii and tibialis
      anterior was higher than that of all other muscles, and females had higher echo
      intensity than males. Moreover, the muscle echo intensity was positively
      correlated with the subcutaneous layer thickness in three of five muscles.
      CONCLUSION: The echo intensity reliability was function of the ROI size. Muscle
      and gender variability in echo intensity was likely due to differences in fibrous
      and adipose tissue content and distribution. Possible explanations for the
      observed correlations between muscle echo intensity and subcutaneous layer
      thickness include the dependence of both variables on total body adiposity or the
      direct dependence of the extent of intramuscular fat on the amount of
      subcutaneous fat.

PMID- 24902992
TI  - Cardiovascular adaptations to 4 and 12 months of football or strength training in
      65- to 75-year-old untrained men.
AB  - The study examined the effects of 1 year of football or strength training on
      cardiovascular function in 65- to 75-year-old men. Twenty-six untrained men (age:
      68.2 +/- 3.2 years) were randomized to football training (FTG; n = 9), strength
      training (STG; n = 9), or control (CG; n = 8). In FTG, left ventricular (LV)
      internal diastolic diameter, end-diastolic volume, and mass index were 8%, 21%,
      and 18% higher (P < 0.01), respectively, after 12 months, with no changes in STG
      and CG. After 12 months, LV ejection fraction was increased (P < 0.05) by 8% and
      5% in FTG and STG, respectively, and systolic longitudinal two-dimensional strain
      by 8% and 6%, whereas right ventricular systolic function improved (P < 0.05) by
      22% in FTG, but not in STG and CG. In FTG, LV diastolic mitral inflow (E/A) ratio
      and peak early diastolic velocity (E') improved (P < 0.05) by 25% and 12%,
      respectively, after 12 months, with no changes in STG and CG. In FTG, maximum
      oxygen uptake was 16% and 18% higher (P < 0.001) after 4 and 12 months,
      respectively, and resting heart rate was 6 and 8 beats per minute lower (P <
      0.001), respectively, with no changes in STG and CG. In conclusion, football
      training elicited superior cardiovascular effects compared with strength training
      in elderly untrained men.

PMID- 24902994
TI  - Histologic confirmation of neuronal cell bodies along the spinal accessory nerve.
AB  - INTRODUCTION: Most sources conclude that the spinal accessory nerve (SAN) is a
      purely motor nerve. There are some reports that suggest a sensory component,
      although the exact nature of such sensory fibers has yet to be elucidated. With
      such discrepancies in the literature and with well-established pain syndromes of
      unknown etiology following SAN injury, the authors performed the present study to
      better clarify this anatomy. MATERIALS AND METHODS: The entire accessory nerve
      was harvested from 10 adult cadavers. Samples were then submitted for
      immunohistochemical analyses. RESULTS: Occasional microganglia cells were
      identified along the SAN in all specimens. These ganglia were most numerous along
      the intracranial segment of the SAN, but none was found along the cranial
      rootlets of the accessory nerve. CONCLUSIONS: Neuronal cell bodies were
      identified along the course of the SAN in human cadavers. Although the function
      is not certain, such cells have been found in other animals to be nocioceptive in
      nature. Pending further study, these cells may be found to be involved in
      enigmatic pain syndromes thought to arise in the sternocleidomastoid and
      trapezius muscles.

PMID- 24902993
TI  - Real-time cell cycle imaging during melanoma growth, invasion, and drug response.
AB  - Solid cancers are composed of heterogeneous zones containing proliferating and
      quiescent cells. Despite considerable insight into the molecular mechanisms
      underlying aberrant cell cycle progression, there is limited understanding of the
      relationship between the cell cycle on the one side, and melanoma cell motility,
      invasion, and drug sensitivity on the other side. Utilizing the fluorescent
      ubiquitination-based cell cycle indicator (FUCCI) to longitudinally monitor
      proliferation and migration of melanoma cells in 3D culture and in vivo, we found
      that invading melanoma cells cycle actively, while G1-arrested cells showed
      decreased invasion. Melanoma cells in a hypoxic environment or treated with
      mitogen-activated protein kinase pathway inhibitors remained G1-arrested for
      extended periods of time, with proliferation and invasion resuming after re
      exposure to a more favorable environment. We challenge the idea that the invasive
      and proliferative capacity of melanoma cells are mutually exclusive and further
      demonstrate that a reversibly G1-arrested subpopulation survives in the presence
      of targeted therapies. 

PMID- 24902995
TI  - A modified adrenal gland-sparing surgery based on retroperitoneal laparoscopic
      radical nephrectomy.
AB  - BACKGROUND: The objective of this study was to modify the adrenal gland-sparing
      strategy based on retroperitoneal laparoscopic radical nephrectomy by reviewing
      the anatomic relationship between the kidney and the adrenal gland. METHODS: From
      June 2010 to October 2012, a total of 68 patients (45 males and 23 females) with
      localized renal cell carcinoma were treated at our hospital. The study included
      35 cases that were right side and 33 cases that were left, and average patient
      age was 54.06 years. The average tumor size was 4.7 cm. Tumors were classified
      via the TNM staging system. All patients underwent adrenal gland-sparing surgery
      based on retroperitoneal laparoscopic radical nephrectomy. RESULTS: For each
      patient, surgery was successful without conversion to open surgery. The average
      operative time was 56.65 +/- 26.60 min, and the mean blood loss was 70.61 +/-
      60.96 ml. All patients were discharged from the hospital 3 to 8 days after
      surgery. During surgery, the adrenal gland was slightly lacerated in three cases
      and the peritoneum showed perforation in six cases. Only one case recurred during
      the study follow-up. CONCLUSIONS: Based on retroperitoneal laparoscopy radical
      nephrectomy, this effective adrenal gland-sparing surgery showed direct exposure
      of tissue and little interference of the upper pole of the kidney. Elevation of
      the adrenal gland could help with the complete dissection of the adrenal gland
      from the kidney. The separation of the kidney was rapid, simple and accurate. The
      probability of adrenal gland damage was reduced. This strategy is recommended for
      widespread use in T1-2 renal neoplasms.

PMID- 24902996
TI  - A review of the literature regarding stress among nursing students during their
      clinical education.
AB  - BACKGROUND: There has been increased attention in the literature about stress
      among nursing students. It has been evident that clinical education is the most
      stressful experience for nursing students. AIM: The aim of this paper was to
      critically review studies related to degrees of stress and the type of stressors
      that can be found among undergraduate nursing students during their clinical
      education. METHODS: The search strategy involved the utilization of the following
      databases: MEDLINE (Medical Literature on-Line), CINAHL (Cumulative Index to
      Nursing and Allied Health Literature), PsycINFO (Psychology Information) and
      PubMed. Keywords were stress, undergraduate nursing students, clinical practice.
      The review included those studies published between 2002 and 2013, conducted in
      any country as long as reported in English, and including a focus on the clinical
      practice experience of nursing students. Thirteen studies met the eligibility
      criteria. RESULTS: Four themes were identified: initial clinical experience,
      comparison between different academic years, cross-cultural comparison, and
      eustress aspects of clinical experience. IMPLICATIONS FOR NURSING AND HEALTH
      POLICY: This review expands current knowledge in the area of stress in clinical
      settings and calls for further research. Nursing teachers should utilize the
      findings of this review to direct their students during clinical practice.
      Moreover, hospital administrators need to promote policies to promote a training
      environment where students are supported and inspired.

PMID- 24902998
TI  - Association of a behaviorally based high school health education curriculum with
      increased exercise.
AB  - Increasing exercise in children and adolescents through academic classes is an
      understudied area. Potential benefits include associated improvements in health,
      psychosocial, and quality-of-life factors. A sample of 98 students (M(age) =
      14.3) from high school health education classes received six, 40-min lessons
      incorporating cognitive-behavioral methods to increase exercise over 6 weeks.
      Significant within-group improvements in exercise, mood, and body satisfaction
      were found, with slightly larger effect sizes identified for the boys. Increase
      in exercise was significantly associated with reduced mood distress (beta = -.17,
      p < .001). For the girls only, change in body satisfaction significantly mediated
      that relationship, and a reciprocal relationship between changes in mood and body
      satisfaction was also identified. Incorporation of lessons emphasizing goal
      setting and self-regulation within high school health education classes may
      foster increased exercise and associated improvements in mood and body
      satisfaction. For girls, the positive effects may reinforce one another.

PMID- 24902997
TI  - Urinary podocyte excretion and proteinuria in patients treated with antivascular
      endothelial growth factor therapy for solid tumor malignancies.
AB  - BACKGROUND: Urinary podocyte excretion (podocyturia) may function as a more
      specific marker of ongoing glomerular damage. This study sought to analyze the
      relationship between proteinuria and podocyturia in cancer patients treated with
      antivascular endothelial growth factor (anti-VEGF) agents. METHODS: Thirty-seven
      patients treated with anti-VEGF medications were analyzed in a single
      institution, cross-sectional study. Podocyte cultures were performed on random
      urine collections (50-100 ml), and podocytes were identified by positive podocin
      staining. The corresponding urine samples were analyzed for protein and
      creatinine (Cr) measurements. RESULTS: Proteinuria >=0.5 g/g Cr was found in 30%
      of the patients (median, 0.12; interquartile range, 0.04-0.86), and 62% had
      podocyturia. There was a significant difference in the amount of podocyturia
      between patients with proteinuria >=0.5 g/g Cr and those with a value <0.5 g/g Cr
      (median podocyturia, 1.08 cells/mg Cr, range, 0-14.55 vs. 0.03 cells/mg Cr,
      range, 0-1.64, respectively; p < 0.001). A statistically significant correlation
      was observed between the cumulative dose of bevacizumab and both proteinuria (r =
      0.48, p = 0.004) and podocyturia (r = 0.34, p = 0.045) as well as between
      proteinuria and podocyturia (r = 0.63, p < 0.001), suggesting that these are
      mechanistically related. DISCUSSION: Ongoing podocyte loss may be mechanistically
      related to the onset and severity of proteinuria in patients treated with anti
      VEGF agents.

PMID- 24902999
TI  - Lung volume reduction coil treatment in chronic obstructive pulmonary disease
      patients with homogeneous emphysema: a prospective feasibility trial.
AB  - BACKGROUND: In patients with heterogeneous emphysema, surgical and bronchoscopic
      lung volume reduction (LVR) treatments are available. However, for patients with
      homogeneous emphysema these treatments are hardly investigated and seem less
      effective. Bronchoscopic LVR coil treatment has been shown to be effective in
      patients with heterogeneous emphysema, but this treatment has not been
      exclusively investigated in homogeneous emphysema. OBJECTIVES: The aim of this
      study was to investigate the safety and efficacy of LVR coil treatment in
      patients with homogeneous emphysema. METHODS: In this single-arm, open-label
      study, patients received a maximum of 12 LVR coils (PneumRx Inc., Mountain View,
      Calif., USA) in each upper lobe in two sequential procedures. Tests were
      performed at baseline and at 6 months. The primary endpoint was the improvement
      from baseline in 6-min walking distance (6MWD) after treatment. RESULTS: Ten
      patients with severe airway obstruction and hyperinflation were treated. A median
      of 11 (range 10-12) coils were placed in each lung. Two chronic obstructive
      pulmonary disease exacerbations and one small pneumothorax were recorded as
      serious adverse events. At 6 months, 6MWD had improved from 289 to 350 m (p =
      0.005); forced vital capacity from 2.17 to 2.55 liters (p = 0.047); residual
      volume from 5.04 to 4.44 liters (p = 0.007) and St. George's Respiratory
      Questionnaire from 63 to 48 points (p = 0.028). CONCLUSION: LVR coil treatment in
      homogeneous patients improves hyperinflation, airway resistance, exercise
      capacity and quality of life with an acceptable safety profile. The benefit of
      LVR coil treatment is not limited to patients with heterogeneous emphysema, and
      patients with homogenous emphysema can benefit as well.

PMID- 24903001
TI  - Practices and preferences for detecting chronic medication toxicity: a pilot
      cross-sectional survey of health care providers focusing on decision support
      systems.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Adverse drug reactions (ADRs) are a critical
      concern: they are costly, both in dollars and in diminishing patients' quality of
      life. ADRs that occur due to prolonged exposure to a pharmaceutical agent
      (adverse drug reactions of long latency, ADRLLs) may be easier to prevent than
      acute ADRs, as ADRLLs inherently require continued medication exposures. This
      pilot study used glucocorticoid-induced osteoporosis (GIO) as an example ADRLL.
      The aims were to survey health care providers' current practices in avoiding
      ADRLLs and the perceived utility of decisional support systems (DSS) to aid them
      in preventing GIO. METHODS: We administered an anonymous, cross-sectional survey
      to health care providers (fellows, doctor assistants, nurse practitioners and
      attending doctors) focusing on their methods to monitor for and prevent ADRLLs.
      The questionnaire also gauged usage of electronic medical records (EMRs) and each
      provider's perceived utility of specific DSS-based approaches to monitoring for
      GIO. Data were interpreted using descriptive statistics and histograms. RESULTS:
      A majority of the 33 responding providers (84.8%) reported that their primary
      ADRLL avoidance technique is simply remembering that a patient is on chronic
      glucocorticoids. The most favourably perceived DSS options included tracking
      medications on a flow sheet (84.8%) and digital tracking of cumulative
      glucocorticoid exposure with real-time prompts (83.9%). CONCLUSIONS: Surveyed
      providers reported that additional DSS implementation may help in the avoidance
      of ADRLLs such as GIO. Providers ranked both digital and non-digital DSS
      favourably, but a computerized approach is appealing in that it may be integrated
      into extant EMR systems.

PMID- 24903000
TI  - Autophagy correlates with maintenance of salivary gland function following
      radiation.
AB  - The current standard of care for head and neck cancer includes surgical resection
      of the tumor followed by targeted head and neck radiation. This radiotherapy
      results in a multitude of negative side effects in adjacent normal tissues.
      Autophagy is a cellular mechanism that could be targeted to ameliorate these side
      effects based on its role in cellular homeostasis. In this study, we utilized
      Atg5(f/f);Aqp5-Cre mice which harbor a conditional knockout of Atg5, in salivary
      acinar cells. These autophagy-deficient mice display increased radiosensitivity.
      Treatment of wild-type mice with radiation did not robustly induce autophagy
      following radiotherapy, however, using a model of preserved salivary gland
      function by IGF-1-treatment prior to irradiation, we demonstrate increased
      autophagosome formation 6-8 hours following radiation. Additionally,
      administration of IGF-1 to Atg5(f/f);Aqp5-Cre mice did not preserve physiological
      function. Thus, autophagy appears to play a beneficial role in salivary glands
      following radiation and pharmacological induction of autophagy could alleviate
      the negative side effects associated with therapy for head and neck cancer. 

PMID- 24903002
TI  - Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on
      circulating steroid levels in healthy subjects.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are
      widely used psychoactive substances. MDMA primarily enhances serotonergic
      neurotransmission, and methylphenidate increases dopamine but has no serotonergic
      effects. Both drugs also increase norepinephrine, resulting in sympathomimetic
      properties. Here we studied the effects of MDMA and methylphenidate on 24-hour
      plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with
      single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate,
      and placebo on 4 separate days using a cross-over study design. Cortisol,
      cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11
      deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone
      sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to
      24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly
      increased the plasma concentrations of cortisol, corticosterone, 11
      dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately
      increase aldosterone levels compared with placebo. MDMA also increased the sum of
      cortisol + cortisone and the cortisol/cortisone ratio, consistent with an
      increase in glucocorticoid production. MDMA did not alter the levels of
      cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not
      affect any of the steroid concentrations, and it did not change the effects of
      MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute
      effects on circulating steroids. These effects are not observed after stimulation
      of the dopamine and norepinephrine systems with methylphenidate. The present
      findings support the view that serotonin rather than dopamine and norepinephrine
      mediates the acute pharmacologically induced stimulation of the hypothalamic
      pituitary-adrenal axis in the absence of other stressors.

PMID- 24903003
TI  - Test-retest reliability of an insole plantar pressure system to assess gait along
      linear and curved trajectories.
AB  - BACKGROUND: Previous studies have assessed reliability of insole technology for
      evaluating foot pressure distribution during linear walking. Since in natural
      motion straight walking is intermingled with turns, we determined the test-retest
      reliability of insole assessment for curved as well as linear trajectories, and
      estimated the minimum number of steps required to obtain excellent reliability
      for each output variable. METHODS: Sixteen young healthy participants were
      recruited. Each performed, two days apart, two sessions of three walking
      conditions: linear (LIN) and curved, clockwise (CW) and counter-clockwise (CCW).
      The Pedar-X system was used to collect pressure distribution. Foot print was
      analyzed both as a whole and as subdivided into eight regions: medial and lateral
      heel, medial and lateral arch, I metatarsal head, II-V metatarsal heads, hallux,
      lateral toes. Reliability was assessed by using intraclass correlation
      coefficient (ICC) for clinically relevant variables from analysis of 50 steps per
      trajectory: Peak Force (PF); Peak Pressure (PP); Contact Area (CA); Stance
      Duration (S). RESULTS: When considering whole-foot, all variables showed an ICC
      >0.80, therefore highly reliable. This was true for both LIN and curved
      trajectories. There was no difference in ICC of the four variables between left
      and right foot. When collapsing foot and trajectories, S had a lower ICC than PP
      and CA, and PP lower than CA. Mean percent error between the values of first and
      second session was <5%. When separately considering the eight foot regions, ICCs
      of PF, PP and CA for all regions and trajectories were generally >0.90,
      indicating excellent reliability. In curved trajectories, S showed smaller ICCs.
      Since the least ICC value for S was 0.60 in LIN trajectory, we estimated that to
      achieve an ICC >=0.90 more than 200 steps should be collected. CONCLUSIONS: High
      reliability of insole dynamic variables (PF, PP, CA) is obtained with 50 steps
      using the Pedar-X system. On the contrary, high reliability of temporal variable
      (S) requires a larger step number. The negligible differences in ICC between LIN
      and curved trajectory allow use of this device for gait assessment along mixed
      trajectories in both clinical and research setting.

PMID- 24903004
TI  - Bicuspid aortic valve morphology and associated cardiovascular abnormalities in
      fetal Turner syndrome: a pathomorphological study.
AB  - INTRODUCTION: Bicuspid aortic valve (BAV) is common in Turner syndrome (TS). In
      adult TS, 82-95% of BAVs have fusion of the right and left coronary leaflets.
      Data in fetal stages are scarce. The purpose of this study was to gain insight
      into aortic valve morphology and associated cardiovascular abnormalities in a
      fetal TS cohort with adverse outcome early in development. MATERIAL AND METHODS:
      We studied post-mortem heart specimens of 36 TS fetuses and 1 TS newborn.
      RESULTS: BAV was present in 28 (76%) hearts. BAVs showed fusion of the right and
      left coronary leaflet (type 1 BAV) in 61%, and fusion of the right coronary and
      non-coronary leaflet (type 2 BAV) in 39%. There were no significant differences
      in occurrence of additional cardiovascular abnormalities between type 1 and type
      2 BAV. However, all type 2 BAV hearts showed ascending aorta hypoplasia and
      tubular hypoplasia of the B segment, as opposed to only 55 and 64% of type 1 BAV
      hearts, respectively. DISCUSSION: The proportion of type 2 BAV seems higher in TS
      fetuses than in adults. Fetal type 2 BAV hearts all had severe aortic pathology,
      possibly contributing to a worse prognosis of type 2 than type 1 BAV in TS.

PMID- 24903005
TI  - A comprehensive analysis of middle-European molecular sensitization profiles to
      pollen allergens.
AB  - Molecular diagnosis of allergy and microarray technology have opened a completely
      new avenue of insight into sensitization profiles from both the clinical and the
      epidemiological point of view. We used this innovative tool in the description of
      sensitization patterns in pollen-sensitized patients in Middle Europe.
      Immunoglobulin E detection using 112 different allergenic molecules was carried
      out employing the ImmunoCAP ISAC microarray system. Sera from 826 patients
      sensitized to at least one pollen-derived molecule were subjected to analysis.
      The highest observed sensitization rate was 81.0% to grass-specific molecules
      (the most frequent being Phl p 1; 69.6%). The second most frequent sensitization
      was 54.8% to Betulaceae-specific molecules (Bet v 1; 54.2%). Together, grasses
      and Betulaceae components (and their cosensitizations with other components)
      comprised the vast majority of pollen sensitizations. Unexpectedly frequently
      observed sensitizations were those to Cupressaceae-specific molecules (14.1%),
      Oleaceae-specific molecules (10.8%), and the plane tree-derived molecule Pla a 2
      (15.5%). The sensitization rates for all other molecules were within the expected
      range (Art v 1, 13.6%; Pla l 1, 9.6%; Che a 1, 8.4%; Par j 2, 0.9%; Amb a 1,
      0.8%, and Sal k 1, 0.5%). Cross-reacting molecule sensitization rates were found
      to be 12.4% for profilins, 5.0% for polcalcins, and 6.4% for lipid transfer
      proteins. Molecular diagnosis of allergy gives a more precise and comprehensive
      insight into pollen sensitization patterns than extract-based testing, allowing a
      better understanding of the sensitization process and regional differences. The
      data presented here may help to improve the diagnostic and allergen-specific
      treatment procedures in the respective region.

PMID- 24903007
TI  - Prebiotics in healthy infants and children for prevention of acute infectious
      diseases: a systematic review and meta-analysis.
AB  - Prebiotics, defined as nondigestible dietary ingredients resistant to gastric
      acidity and fermented by the intestinal flora, are used to positively influence
      the composition of intestinal flora, thereby promoting health benefits. The
      objective of this systematic review was to assess the efficacy of prebiotics in
      the prevention of acute infectious diseases in children. A systematic literature
      search was conducted using the Ovid Medline, Scopus, Web of Science, and Cochrane
      Library's Central databases. Finally, five randomized controlled trials, all of
      them investigating infants and children 0-24 months of age, were included in the
      review. Pooled estimates from three studies revealed a statistically significant
      decrease in the number of infectious episodes requiring antibiotic therapy in the
      prebiotic group as compared with the placebo group (rate ratio 0.68; 95%
      confidence interval 0.61-0.77). Studies available indicate that prebiotics may
      also be effective in decreasing the rate of overall infections in infants and
      children 0-24 months of age. Further studies in the age group 3-18 years are
      required to determine whether prebiotics can be considered for the prevention of
      acute infectious diseases in the older pediatric population. 

PMID- 24903008
TI  - Tunable white-light emission from mixed lanthanide (Eu3+, Gd3+, Tb3+)
      coordination polymers derived from 4-(dipyridin-2-yl)aminobenzoate.
AB  - Herein, we have developed a series of isostructural mixed Ln(3+)-4-(dipyridin-2
      yl)aminobenzoate coordination polymers [Ln(3+) = Eu(3+) (1), Tb(3+) (2), and
      Gd(3+) (3)], and characterized and investigated their photophysical properties.
      The results demonstrated that by gently tuning the excitation wavelength of these
      mixed lanthanide complexes, white light emission can be realized with the
      Commission Internationale de I'Eclairage coordinates (0.32, 0.34). Furthermore,
      by changing the concentration profiles of lanthanide ions stoichiometrically in
      mixed-lanthanide complexes and exciting at particular wavelengths, various
      emission colours can also be successfully obtained. The antenna ligand, 4
      (dipyridin-2-yl)aminobenzoic acid, provides an efficient energy transfer for the
      sensitization of Eu(3+) and Tb(3+) complexes and exhibits red and green
      emissions, respectively. Most importantly, due to the high energy (32,150 cm(-1))
      of the Gd(3+) ion lowest-lying emission level, the corresponding Gd(3+) complex
      displays ligand-centered visible emission in the blue light region, and hence it
      acts as a blue emitter. Therefore, Eu(3+) and Tb(3+) complexes in conjunction
      with a Gd(3+) complex is a suitable choice to obtain tunable white-light-emission
      from Ln(3+) coordination polymers. The morphological analyses of the mixed
      lanthanide coordination polymers by transmission electron microscopy (TEM)
      disclose that these compounds exist as unique crystalline nano-rods with an
      average diameter of 200 nm. The developed mixed lanthanide complexes also exhibit
      high thermal stability (~420  degrees C).

PMID- 24903010
TI  - Methylthiodeoxynivalenol (MTD): insight into the chemistry, structure and
      toxicity of thia-Michael adducts of trichothecenes.
AB  - Methylthiodeoxynivalenol (MTD), a novel derivative of the trichothecene mycotoxin
      deoxynivalenol (DON), was prepared by applying a reliable procedure for the
      formal Michael addition of methanethiol to the conjugated double bond of DON.
      Structure elucidation revealed the preferred formation of the hemiketal form of
      MTD by intramolecular cyclisation between C8 and C15. Computational
      investigations showed a negative total reaction energy for the hemiketalisation
      step and its decrease in comparison with theoretical model compounds. Therefore,
      this structural behaviour seems to be a general characteristic of thia-Michael
      adducts of type B trichothecenes. MTD was shown to be less inhibitory for a
      reticulocyte lysate based in vitro translation system than the parent compound
      DON, which supports the hypothesis that trichothecenes are detoxified through
      thia-adduct formation during xenobiotic metabolism. 

PMID- 24903009
TI  - Indoleamine 2,3-dioxygenase 1 (IDO1) activity in leukemia blasts correlates with
      poor outcome in childhood acute myeloid leukemia.
AB  - Microenvironmental factors contribute to the immune dysfunction characterizing
      acute myeloid leukemia (AML). Indoleamine 2,3-dioxygenase 1 (IDO1) is an
      interferon (IFN)-gamma-inducible enzyme that degrades tryptophan into kynurenine,
      which, in turn, inhibits effector T cells and promotes regulatory T-cell (Treg)
      differentiation. It is presently unknown whether childhood AML cells express IDO1
      and whether IDO1 activity correlates with patient outcome. We investigated IDO1
      expression and function in 37 children with newly diagnosed AML other than acute
      promyelocytic leukemia. Blast cells were cultured with exogenous IFN-gamma for 24
      hours, followed by the measurement of kynurenine production and tryptophan
      consumption. No constitutive expression of IDO1 protein was detected in blast
      cells from the 37 AML samples herein tested. Conversely, 19 out of 37 (51%) AML
      samples up-regulated functional IDO1 protein in response to IFN-gamma. The
      inability to express IDO1 by the remaining 18 AML samples was not apparently due
      to a defective IFN-gamma signaling circuitry, as suggested by the measurement of
      signal transducer and activator of transcription 3 (STAT3) phosphorylation. Co
      immunoprecipitation assays indicated the occurrence of physical interactions
      between STAT3 and IDO1 in AML blasts. In line with this finding, STAT3 inhibitors
      abrogated IDO1 function in AML blasts. Interestingly, levels of IFN-gamma were
      significantly higher in the bone marrow fluid of IDO-expressing compared with IDO
      nonexpressing AMLs. In mixed tumor lymphocyte cultures (MTLC), IDO-expressing AML
      blasts blunted the ability of allogeneic naive T cells to produce IFN-gamma and
      promoted Treg differentiation. From a clinical perspective, the 8-year event-free
      survival was significantly worse in IDO-expressing children (16.4%, SE 9.8) as
      compared with IDO-nonexpressing ones (48.0%, SE 12.1; p=0.035). These data
      indicate that IDO1 expression by leukemia blasts negatively affects the prognosis
      of childhood AML. Moreover, they speak in favor of the hypothesis that IDO can be
      targeted, in adjunct to current chemotherapy approaches, to improve the clinical
      outcome of children with AML. 

PMID- 24903011
TI  - Intelligent telemetric stent for wireless monitoring of intravascular pressure
      and its in vivo testing.
AB  - This paper reports a sensor-integrated telemetric stent targeted at wireless
      detection and monitoring of restenosis, a common vascular complication induced by
      stent implantation. The developed "smart" stent incorporates the design and
      fabrication approaches that raise the practicality of the device, being tested in
      an in vivo study that validates its operating principle. The stent is produced to
      have a gold-coated helical-like structure that serves as a high-performance
      inductor/antenna and integrated with a novel capacitive pressure sensor chip, all
      based on medical-grade stainless steel. The stent device forms an inductor
      capacitor resonant tank that enables radio-frequency (RF) wireless pressure
      sensing in an operating frequency range of 30-80 MHz. With an overall length of
      20 mm, the device is designed to be compatible with standard balloon catheters
      and necessary crimping process. The balloon-expanded devices are characterized in
      saline and blood to determine selective coating of passivation layer, Parylene C,
      with tailored thicknesses in order to maximize both RF and sensing abilities. In
      vitro testing of the devices reveals a frequency sensitivity up to 146 ppm/mmHg
      over a pressure range of 250 mmHg. Tests in pig models show wireless detection of
      device's resonance and frequency response to variations in local blood pressure,
      the targeted function of the device. 

PMID- 24903012
TI  - Confined growth of carbon nanoforms in one-dimension by fusion of anthracene
      rings inside the pores of MCM-41.
AB  - We report a simple two-step procedure that uses anthracene, a cheap polyaromatic
      hydrocarbon with low melting point, as a molecular precursor to produce carbon
      nanoforms (CNFs). First, we describe the chemical synthesis of graphite from the
      fusion of anthracene rings at relatively low temperature (520  degrees C)
      followed by cyclodehydrogenation. Next, we extend this protocol to the synthesis
      of CNFs by confining the molecular precursor in a mesoporous host like MCM-41.
      The confined environment favors one-dimensional growth of CNFs with sizes
      controlled by the pores of the mesoporous host. 

PMID- 24903013
TI  - Enhanced expression of the beta4-galactosyltransferase 2 gene impairs mammalian
      tumor growth.
AB  - Altered N-glycosylation of membrane proteins is associated with malignant
      transformation of cells. We found that the expression of the beta4
      galactosyltransferase 2 (beta4GalT2) gene is decreased markedly during the
      transformation. Here, we examined whether the tumor growth activity of B16-F10
      mouse melanoma cells can be reduced by the enhanced expression of the beta4GalT2
      gene. We isolated a clone, B16-beta4GalT2, showing its beta4GalT2 transcript 2.5
      times higher than a control clone, B16-mock, by transducing its cDNA, and
      transplanted them subcutaneously into C57BL/6 mice to examine their tumor growth
      activity. The results showed that the average size of tumors formed with B16-mock
      cells is 13.1+/-0.76 mm, whereas that of tumors formed with B16-beta4GalT2 cells
      is 5.1+/-1.13 mm (P<0.01) 2 weeks after transplantation. Immunohistochemical
      analyses showed that the apoptosis and the suppression of angiogenesis are
      induced in the tumors upon transduction of the beta4GalT2 gene. To pursue a
      clinical usefulness of the beta4GalT2 gene for suppressing human tumor growth, we
      injected adenoviruses carrying the human beta4GalT2 cDNA into HuH-7 human
      hepatocellular carcinomas developed in severe combined immunodeficient mice, and
      observed marked growth retardation of the tumors. The enhancement of the
      beta4GalT2 gene expression in tumors is one of the promising approaches to
      suppress human tumor growth. 

PMID- 24903014
TI  - Experimental virotherapy of chemoresistant pancreatic carcinoma using infectivity
      enhanced fiber-mosaic oncolytic adenovirus.
AB  - Pancreatic cancer is a significant clinical problem and novel therapeutic
      approaches are desperately needed. Recent advances in conditionally replicative
      adenovirus-based (CRAd) oncolytic virus design allow the application of CRAd
      vectors as a therapeutic strategy to efficiently target and eradicate
      chemoresistant pancreatic cancer cells, thereby improving the efficacy of
      pancreatic cancer treatment. The goal of this study was to construct and validate
      the efficacy of an infectivity-enhanced, liver-untargeted, tumor-specific CRAd
      vector. A panel of CRAds has been derived that embodies the C-X-C chemokine
      receptor type 4 promoter for conditional replication, two-fiber complex mosaicism
      for targeting expansion and hexon hypervariable region 7 (HVR7) modification for
      liver untargeting. We evaluated CRAds for cancer virotherapy using a human
      pancreatic tumor xenograft model. Employment of the fiber mosaic approach
      improved CRAd replication in pancreatic tumor xenografts. Substitution of the
      HVR7 of the Ad5 hexon for Ad serotype 3 hexon resulted in decreased liver tropism
      of systemically administrated CRAd. Obtained data demonstrated that employment of
      complex mosaicism increased efficacy of the combination of oncolytic virotherapy
      with chemotherapy in a human pancreatic tumor xenograft model. 

PMID- 24903016
TI  - Comparison of two models of surgical care for patients with clefts in Peru.

PMID- 24903015
TI  - Inhibition of mTOR with everolimus and silencing by vascular endothelial cell
      growth factor-specific siRNA induces synergistic antitumor activity in multiple
      myeloma cells.
AB  - Angiogenesis has an important role in the pathogenesis and progression of
      multiple myeloma (MM). MM cells secrete vascular endothelial growth factor
      (VEGF), which further promotes proliferation of the tumor cells. Therefore, we
      evaluated the anti-myeloma effect of VEGF small interfering RNA (siRNA) silencing
      in MM cells and whether it can be augmented by the additional inhibition of the
      mammalian target of rapamycin (mTOR) by everolimus. We shown that everolimus
      inhibits cell growth of MM cells and other leukemic cells at low concentrations
      in a dose-dependent manner. After transfection with VEGF siRNA we observed a
      reduction of cell growth and VEGF expression in all studied cell lines: OPM-2,
      RPMI-8226, INA-6, JURKAT and RAJI. VEGF siRNA both significantly induced
      apoptosis and inhibited proliferation in OPM-2 cells (P<0.0001), RPMI-8226
      (P<0.0001) and in INA-6 (P<0.01) versus controls. Co-treatment with VEGF siRNA
      and everolimus in MM cells resulted in an exaggerated inhibition of proliferation
      compared with VEGF siRNA or everolimus alone (P<0.0001) and enhanced induction of
      apoptosis compared with VEGF siRNA alone (P<0.03). In addition, the combination
      of VEGF siRNA and everolimus significantly reversed P-glycoprotein expression
      (P<0.005) and HIF-1alpha expression (P<0.001) of MM cells, respectively. Our data
      suggest that mTOR inhibition and silencing of VEGF expression is associated with
      synergistic antitumor activity and this combination treatment might be a suitable
      strategy for new therapeutic approaches using RNA interference in MM. 

PMID- 24903017
TI  - Efficient detection of contagious outbreaks in massive metropolitan encounter
      networks.
AB  - Physical contact remains difficult to trace in large metropolitan networks,
      though it is a key vehicle for the transmission of contagious outbreaks. Co
      presence encounters during daily transit use provide us with a city-scale time
      resolved physical contact network, consisting of 1 billion contacts among 3
      million transit users. Here, we study the advantage that knowledge of such co
      presence structures may provide for early detection of contagious outbreaks. We
      first examine the "friend sensor" scheme--a simple, but universal strategy
      requiring only local information--and demonstrate that it provides significant
      early detection of simulated outbreaks. Taking advantage of the full network
      structure, we then identify advanced "global sensor sets", obtaining substantial
      early warning times savings over the friends sensor scheme. Individuals with
      highest number of encounters are the most efficient sensors, with performance
      comparable to individuals with the highest travel frequency, exploratory behavior
      and structural centrality. An efficiency balance emerges when testing the
      dependency on sensor size and evaluating sensor reliability; we find that
      substantial and reliable lead-time could be attained by monitoring only 0.01% of
      the population with the highest degree.

PMID- 24903018
TI  - Raising awareness of new psychoactive substances: chemical analysis and in vitro
      toxicity screening of 'legal high' packages containing synthetic cathinones.
AB  - The world's status quo on recreational drugs has dramatically changed in recent
      years due to the rapid emergence of new psychoactive substances (NPS),
      represented by new narcotic or psychotropic drugs, in pure form or in
      preparation, which are not controlled by international conventions, but that may
      pose a public health threat comparable with that posed by substances listed in
      these conventions. These NPS, also known as 'legal highs' or 'smart drugs', are
      typically sold via Internet or 'smartshops' as legal alternatives to controlled
      substances, being announced as 'bath salts' and 'plant feeders' and is often
      sought after for consumption especially among young people. Although NPS have the
      biased reputation of being safe, the vast majority has hitherto not been tested
      and several fatal cases have been reported, namely for synthetic cathinones, with
      pathological patterns comparable with amphetamines. Additionally, the
      unprecedented speed of appearance and distribution of the NPS worldwide brings
      technical difficulties in the development of analytical procedures and risk
      assessment in real time. In this study, 27 products commercialized as 'plant
      feeders' were chemically characterized by gas chromatography-mass spectrometry
      and nuclear magnetic resonance spectroscopy. It was also evaluated, for the first
      time, the in vitro hepatotoxic effects of individual synthetic cathinones, namely
      methylone, pentedrone, 4-methylethcathinone (4-MEC) and 3,4
      methylenedioxypyrovalerone (MDPV). Two commercial mixtures ('Bloom' and 'Blow')
      containing mainly cathinone derivatives were also tested, and 3,4
      methylenedioxymethamphetamine (MDMA) was used as the reference drug. The study
      allowed the identification of 19 compounds, showing that synthetic cathinones are
      the main active compounds present in these products. Qualitative and quantitative
      variability was found in products sold with the same trade name in matching or
      different 'smartshops'. In the toxicity studies performed in primary cultured rat
      hepatocytes, pentedrone and MDPV proved to be the most potent individual agents,
      with EC50 values of 0.664 and 0.742 mM, respectively, followed by MDMA (EC50 =
      0.754 mM). 4-MEC and methylone were the least potent substances, with EC50 values
      significantly higher (1.29 and 1.18 mM, respectively; p < 0.05 vs. MDMA). 'Bloom'
      and 'Blow' showed hepatotoxic effects similar to MDMA (EC50 = 0.788 and 0.870 mM,
      respectively), with cathinones present in these mixtures contributing additively
      to the overall toxicological effect. Our results show a miscellany of
      psychoactive compounds present in 'legal high' products with evident hepatotoxic
      effects. These data contribute to increase the awareness on the real composition
      of 'legal high' packages and unveil the health risks posed by NPS.

PMID- 24903019
TI  - Health status, use of healthcare, and socio-economic implications of cancer
      survivorship in Portugal: results from the Fourth National Health Survey.
AB  - PURPOSE: Understanding the morbidity and socio-economic implications of cancer
      survivorship is essential for a comprehensive management of oncological diseases.
      We compared cancer survivors (CS) with the general population regarding health
      status, use of healthcare resources and socio-economic condition. METHODS: We
      analyzed data from a representative sample of the Portuguese population aged >=15
      years (n = 35,229). We defined three groups of CS, according to the time since
      diagnosis and the latest cancer treatment: CS 1 diagnosis within 12 months of
      interview; CS 2 diagnosis more than 12 months before and treatment in the
      previous 12 months; CS 3 diagnosis and treatment more than 12 months before.
      These were compared with the general population, adjusting for differences in
      sex, age, and place of residence. RESULTS: The prevalence of CS was 2.2% (CS 1:
      0.2%; CS 2: 0.9%, CS 3: 1.1%). Self-perceived health status was worse among CS
      and short-time incapacity more frequent among CS 1 and CS 2. Health expenses were
      higher in the early stages of survivorship. Lower household income and financial
      difficulties were more frequent in CS 1 and CS 3 men, respectively. CONCLUSION:
      This study confirmed the higher consumption of healthcare resources and worse
      financial situation among CS. IMPLICATIONS FOR CANCER SURVIVORS: Our study
      provides valuable information for understanding the global impact of cancer
      survivorship.

PMID- 24903020
TI  - Incidence of keloid and risk factors following head and neck surgery.

PMID- 24903022
TI  - Health inequalities in the European Union: an empirical analysis of the dynamics
      of regional differences.
AB  - In a panel setting, we analyse the speed of (beta) convergence of (cause
      specific) mortality and life expectancy at birth in EU countries between 1995 and
      2009. Our contribution is threefold. First, in contrast to earlier literature, we
      allow the convergence rate to vary, and thereby uncover significant differences
      in the speed of convergence across time and regions. Second, we control for
      spatial correlations across regions. Third, we estimate convergence among
      regions, rather than countries, and thereby highlight noteworthy variations
      within a country. Although we find (beta) convergence on average, we also
      identify significant differences in the catching-up process across both time and
      regions. Moreover, we use the coefficient of variation to measure the dynamics of
      dispersion levels of mortality and life expectancy (sigma convergence) and,
      surprisingly, find no reduction, on average, in dispersion levels. Consequently,
      if the reduction of dispersion is the ultimate measure of convergence, then, to
      the best of our knowledge, our study is the first that shows a lack of
      convergence in health across EU regions. 

PMID- 24903021
TI  - Response to BRAF inhibition in melanoma is enhanced when combined with immune
      checkpoint blockade.
AB  - BRAF-targeted therapy results in objective responses in the majority of patients;
      however, the responses are short lived (~6 months). In contrast, treatment with
      immune checkpoint inhibitors results in a lower response rate, but the responses
      tend to be more durable. BRAF inhibition results in a more favorable tumor
      microenvironment in patients, with an increase in CD8(+) T-cell infiltrate and a
      decrease in immunosuppressive cytokines. There is also increased expression of
      the immunomodulatory molecule PDL1, which may contribute to the resistance. On
      the basis of these findings, we hypothesized that BRAF-targeted therapy may
      synergize with the PD1 pathway blockade to enhance antitumor immunity. To test
      this hypothesis, we developed a BRAF(V600E)/Pten(-/-) syngeneic tumor graft
      immunocompetent mouse model in which BRAF inhibition leads to a significant
      increase in the intratumoral CD8(+) T-cell density and cytokine production,
      similar to the effects of BRAF inhibition in patients. In this model, CD8(+) T
      cells were found to play a critical role in the therapeutic effect of BRAF
      inhibition. Administration of anti-PD1 or anti-PDL1 together with a BRAF
      inhibitor led to an enhanced response, significantly prolonging survival and
      slowing tumor growth, as well as significantly increasing the number and activity
      of tumor-infiltrating lymphocytes. These results demonstrate synergy between
      combined BRAF-targeted therapy and immune checkpoint blockade. Although clinical
      trials combining these two strategies are ongoing, important questions still
      remain unanswered. Further studies using this new melanoma mouse model may
      provide therapeutic insights, including optimal timing and sequence of therapy.

PMID- 24903023
TI  - Productivity or discrimination? An economic analysis of excess-weight penalty in
      the Swedish labor market.
AB  - This article investigates the excess-weight penalty in income for men and women
      in the Swedish labor market, using longitudinal data. It compares two
      identification strategies, OLS and individual fixed effects, and distinguishes
      between two main sources of excess-weight penalties, lower productivity because
      of bad health and discrimination. For men, the analysis finds a significant
      obesity penalty related to discrimination when applying individual fixed effects.
      We do not find any significant excess-weight penalty for women. 

PMID- 24903024
TI  - Exercise-induced regulation of matrix metalloproteinases in the skeletal muscle
      of subjects with type 2 diabetes.
AB  - Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) play a
      critical role during vascular remodelling, in both health and disease. Impaired
      MMP regulation is associated with many diabetes-related complications. This study
      examined whether exercise-induced regulation of MMPs is maintained in the
      skeletal muscle of patients with uncomplicated type 2 diabetes (T2DM). Subjects
      [12 T2DM, 9 healthy control subjects (CON)] underwent 8 weeks of physical
      training. Messenger RNA (mRNA) was measured at baseline, during and after 8 weeks
      of training. Protein was measured pre- and post-training. At baseline, there were
      no effects of diabetes on MMP or TIMP mRNA or protein. mRNA and protein response
      to training was similar in both groups, except active MMP-2 protein was elevated
      post training in T2DM only. Our results indicate that exercise-induced
      stimulation of MMPs is preserved in skeletal muscle of patients with T2DM. This
      early stage of diabetes may provide an opportunity for intervention and
      prevention of complications. 

PMID- 24903025
TI  - Neonatal spontaneous pneumomediastinum.

PMID- 24903026
TI  - Repeated cannulation of umbilical hernia with Ventriculoperiotoneal shunt
      catheter.
AB  - Ventriculoperitoneal (VP) shunts are commonly used to manage hydrocephalus in
      both adult and paediatric populations. Whilst infection remains by far the most
      common complication leading to shunt revision other causes need to be considered.
      Our case report examines a 62-year-old female who presents for operative
      management of a Choroid Plexus Papilloma. Post-operatively she develops
      hydrocephalus and is managed with a VP shunt. Interestingly the distal end of the
      catheter cannulated an unknown umbilical hernia twice creating diagnostic
      dilemma. Issues around shunt insertion in the morbidly obese population and the
      basic science behind cerebrospinal fluid reabsorption are explored. Although this
      is a rare complication it should be considered in any post-operative shunt
      patient is slow to recover particularly if they are obese. 

PMID- 24903027
TI  - Determination of oral bioavailability of fusaric acid in male Sprague-Dawley
      rats.
AB  - Head and neck squamous cell cancer accounts for 3 % of new cancer cases and 2 %
      of cancer mortality annually in the United States. Current treatment options for
      most head and neck cancers continue to be surgical excision with or without
      radiation, radiation alone, or chemotherapy with radiation depending on location,
      stage of disease, and patient preference. Fusaric acid (FA) is a novel compound
      from a novel class of nicotinic acid derivatives that have activity against head
      and neck squamous cell carcinoma (HNSCC). Although its exact mechanism is still
      unknown, FA is thought to be active by increasing damage to DNA and preventing
      its synthesis and repair. The novel mechanism of FA provides an alternative to
      present therapies, as a single agent whether given parenterally or orally. It has
      synergy with conventional agents taxol, carboplatin, and erlotinib. In order to
      determine if FA has reasonable oral bioavailability, we have determined the
      pharmacokinetics of FA in male Sprague Dawley rats following administration by
      gavage and by intravenous injection. The bioavailability of FA was sufficient (58
      %) to suggest that FA may be viable as an orally administered medication. Despite
      the encouraging bioavailability of FA, the intravenous (IV) pharmacokinetics
      suggested non-linear behavior within the IV dose range of 10, 25, and 75 mg/kg.
      These results demonstrate that further pharmacokinetic and toxicity studies in
      larger animals such as dogs and non-human primates are warranted.

PMID- 24903028
TI  - Direct interaction between CCN family protein 2 and fibroblast growth factor 1.
AB  - In an attempt to find out a new molecular counterpart of CCN family protein 2
      (CCN2), a matricellular protein with multiple functions, we performed an
      interactome analysis and found fibroblast growth factor (FGF) -1 as one of the
      candidates. Solid-phase binding assay indicated specific binding between CCN2 and
      FGF-1. This binding was also confirmed by surface plasmon resonance (SPR)
      analysis that revealed a dissociation constant (Kd) of 3.98 nM indicating strong
      molecular interaction between the two. RNA analysis suggested that both FGF-1 and
      CCN2 could be produced by chondrocytes and thus their interaction in the
      cartilage is possible. These findings for the first time indicate the direct
      interaction of CCN2 and FGF-1 and suggest the co-presence of these molecules in
      the cartilage microenvironment. CCN2 is a well-known promoter of cartilage
      development and regeneration, whereas the physiological and pathological role of
      FGF-1 in cartilage mostly remains unclear. Biological role of FGF-1 itself in
      cartilage is also suspected. 

PMID- 24903029
TI  - [Cutaneous side effects of anti-tumor therapy with BRAF and MEK inhibitors].
AB  - BACKGROUND: BRAF and MEK inhibitors are new targeted therapies which are used in
      the treatment of malignancies, in particular of malignant melanoma. SIDE EFFECTS:
      Cutaneous side effects are common during the treatment with both types of
      inhibitors. These side effects include inflammatory reactions such as
      maculopapular and papulopustular exanthema, hand-foot syndrome, panniculitis,
      paronychia, photo- and radio-sensitization. As a class effect, BRAF-inhibitors
      induce proliferative disorders of keratinocytes and melanocytes, such as
      palmoplantar hyperkeratosis (as part of the hand-foot syndrome), verruciform and
      acanthoma-like lesions, follicular and Grover disease-like hyperkeratoses,
      keratoacanthomas, squamous cell carcinomas and atypical melanocytic nevi with
      transition to secondary melanomas. Furthermore, hair alterations and xerosis are
      possible. CONCLUSIONS: Treatment with BRAF and MEK inhibitors requires close
      dermatologic monitoring of the patient. This manuscript summarizes the most
      frequent cutaneous side effects and their management.

PMID- 24903030
TI  - [Management of cutaneous lymphomas].
AB  - BACKGROUND: Cutaneous lymphomas challenge both researchers and physicians for
      several reasons. First, their pathogenesis has not been completely elucidated,
      which complicates the development of new curative therapies. DIAGNOSIS: Second,
      the diagnosis depends on a complex combination of clinic, histology,
      immunohistochemistry and molecular biology. Determination of the correct
      diagnosis is important for the patient and clinician because the different types
      of cutaneous lymphomas have very different prognoses and clinical courses,
      knowledge of which is essential for making treatment decisions. THERAPY: Third,
      no curative therapies for cutaneous lymphomas are available, so that the disease
      often relapses even during therapy. Thereby frequent changes in therapy are
      necessary, so that many patients receive a variety of treatments during the
      course of their disease. Many of the established therapeutic agents have a broad
      spectrum of side effects, so that special knowledge and experience with each
      agent is required, as well as careful monitoring. On the basis of more complex
      patient cases, general aspects of the difficult management of cutaneous lymphomas
      are discussed in this article.

PMID- 24903032
TI  - [Gametocyte carriage in asymptomatic Plasmodium falciparum infections in Haiti
      (2010-2013)].
AB  - A survey conducted from May 2010 to October 2013 in five from ten departments of
      Haiti among 5,342 persons aged from 1 to 107 years showed a gametocytic rate =
      3.2%. However, it varies greatly from one Department to another, ranging from
      0.5% in Grande Anse Department to 5.9% in Southeast Department. Malaria is
      present in Haiti in heterogeneous coastal foci. Gametocytes occur at all ages,
      but two times most often in male under 20 years. Entomological studies in Haiti
      are needed to better characterize the relationships between man and the vector
      Anopheles albimanus, adapting the fight more effectively.

PMID- 24903031
TI  - Response to deep brain stimulation in the lateral hypothalamic area in a rat
      model of obesity: in vivo assessment of brain glucose metabolism.
AB  - PURPOSE: To investigate changes in glucose brain metabolism after deep brain
      stimulation (DBS) in the lateral hypothalamic area (LHA) in a rat model of
      obesity. PROCEDURES: Ten obese male Zucker rats were divided into two groups: LHA
      control and LHA-DBS. Concentric bipolar platinum-iridium electrodes were
      implanted bilaterally. After 7 days, DBS was applied for 15 days. Weight and food
      and water intake were monitored. 2-Deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG)
      PET-CT imaging studies were performed the day after the end of DBS. Differences
      in glucose uptake between the groups were assessed with statistical parametric
      mapping. RESULTS: A difference in weight gain of 3.19 percentage points was found
      between groups. Average food consumption during the first 15 days was lower in
      DBS-treated animals than in non-stimulated animals. DBS increased metabolism in
      the mammillary body, subiculum-hippocampal area, and amygdala, while a decrease
      in metabolism was recorded in the thalamus, caudate, temporal cortex, and
      cerebellum. CONCLUSIONS: DBS produced significant changes in brain regions
      associated with the control of food intake and the brain reward system. DBS seems
      to normalize the impaired hippocampal functioning that has been described in
      obese rats. The smaller weight gain in the DBS group suggests that this technique
      could be considered an option for the treatment of obesity.

PMID- 24903033
TI  - CYP2J2 and EETs Protect against Oxidative Stress and Apoptosis in Vivo and in
      Vitro Following Lung Ischemia/Reperfusion.
AB  - BACKGROUND: Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic
      acids to epoxyeicosatrienoic acids (EETs). EETs exert various biological effects,
      including anti-inflammatory, anti-apoptotic, pro-proliferation, pro-angiogenesis,
      anti-oxidation, and anti-fibrosis effects. However, little is known about the
      role of CYP2J2 and EETs in lung ischemia/reperfusion injury. In this study, we
      examined the effects of exogenous EETs or CYP2J2 overexpression on lung
      ischemia/reperfusion injury in vivo and in vitro. METHODS AND RESULTS: CYP2J2
      gene was stably transfected into rat lungs via pcDNA3.1-CYP2J2 plasmid delivery,
      resulting in increased EETs levels in the serum and lung. A rat model of lung
      ischemia/reperfusion injury was developed by clamping the left lung hilum for 1
      hour, followed by reperfusion for 2 hours. We found that CYP2J2 overexpression
      markedly decreased the levels of oxidative stress and cell apoptosis in lung
      tissues induced by ischemia/reperfusion. Moreover, we observed that exogenous
      EETs, or CYP2J2 overexpression, enhanced cell viability, decreased intracellular
      reactive oxygen species (ROS) generation, inhibited mitochondrial dysfunction,
      and attenuated several apoptotic signaling events in a human pulmonary artery
      endothelial cells (HPAECs)-based anoxia/reoxygenation model. These apoptotic
      events included activation of NADPH oxidase, collapse of mitochondrial
      transmembrane potential, and activation of pro-apoptotic proteins and caspase-3.
      These effects were mediated, at least partially, by the PI3K/Akt signaling
      pathway. CONCLUSION: These results reveal that CYP2J2 overexpression and
      exogenous EETs can protect against oxidative stress and apoptosis following lung
      ischemia/reperfusion in vivo and in vitro, suggesting that increasing the level
      of EETs may be a novel promising strategy to prevent and treat lung
      ischemia/reperfusion injury.

PMID- 24903034
TI  - Prevalence and severity of DSM-5 eating disorders in a community cohort of
      adolescents.
AB  - OBJECTIVE: The fifth edition of the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-5) includes a considerably revised eating disorder section. The
      aim of this study was to establish the prevalence and severity of eating
      disorders based on the new DSM-5 criteria in a community cohort of adolescents.
      METHOD: This study is part of TRAILS (TRacking Adolescents' Individual Lives
      Survey), a Dutch cohort study on mental health and social development from
      preadolescence into young adulthood. At baseline, the participants (n = 2,230)
      were about 11 years old. Body mass index was measured at all four assessment
      waves. At age 19, the Composite International Diagnostic Interview was
      administered to 1,584 of the participants. A two-stage screening approach was
      used to estimate the prevalence of DSM-5 eating disorders. Adolescents at high
      risk for eating disorders (n = 312) were selected for an additional interview
      administered by eating disorder experts. RESULTS: Of the high-risk group n = 296
      (95%) could be interviewed. Among the women, the lifetime prevalence of DSM-5
      anorexia nervosa was 1.7%, of bulimia nervosa 0.8% and of binge eating disorder
      2.3%. Eating disorders were relatively rare among the men. The severity of most
      cases was mild to moderate and detection and treatment rates depended on the
      level of severity. DISCUSSION: The most common DSM-5 eating disorder diagnoses in
      adolescents in the community are anorexia nervosa and binge eating disorder.
      Severity ratings for eating disorders seem valid in terms of both the
      distribution in the community and the correlation with detection and treatment by
      health care services.

PMID- 24903035
TI  - [What are guidelines for, what can guidelines do?].

PMID- 24903036
TI  - [Visceral pain. Still a poor relation of pain medicine?].

PMID- 24903037
TI  - [Neurobiology of visceral pain].
AB  - Visceral pain is diffusely localized, referred into other tissues, frequently not
      correlated with visceral traumata, preferentially accompanied by autonomic and
      somatomotor reflexes, and associated with strong negative affective feelings. It
      belongs together with the somatic pain sensations and non-painful body sensations
      to the interoception of the body. (1) Visceral pain is correlated with the
      excitation of spinal (thoracolumbar, sacral) visceral afferents and (with a few
      exceptions) not with the excitation of vagal afferents. Spinal visceral afferents
      are polymodal and activated by adequate mechanical and chemical stimuli. All
      groups of spinal visceral afferents can be sensitized (e.g., by inflammation).
      Silent mechanoinsensitive spinal visceral afferents are recruited by
      inflammation. (2) Spinal visceral afferent neurons project into the laminae I, II
      (outer part IIo) and V of the spinal dorsal horn over several segments, medio
      lateral over the whole width of the dorsal horn and contralateral. Their activity
      is synaptically transmitted in laminae I, IIo and deeper laminae to viscero
      somatic convergent neurons that receive additionally afferent synaptic (mostly
      nociceptive) input from the skin and from deep somatic tissues of the
      corresponding dermatomes, myotomes and sclerotomes. (3) The second-order neurons
      consist of excitatory and inhibitory interneurons (about 90 % of all dorsal horn
      neurons) and tract neurons activated monosynaptically in lamina I by visceral
      afferent neurons and di- or polysynaptically in deeper laminae. (4) The
      sensitization of viscero-somatic convergent neurons (central sensitization) is
      dependent on the sensitization of spinal visceral afferent neurons, local spinal
      excitatory and inhibitory interneurons and supraspinal endogenous control
      systems. The mechanisms of this central sensitization have been little explored.
      (5) Viscero-somatic tract neurons project through the contralateral ventrolateral
      tract and presumably other tracts to the lower and upper brain stem, the
      hypothalamus and via the thalamus to various cortical areas. (6) Visceral pain is
      presumably (together with other visceral sensations and nociceptive as well as
      non-nociceptive somatic body sensations) primarily represented in the posterior
      dorsal insular cortex (primary interoceptive cortex). This cortex receives in
      primates its spinal synaptic inputs mainly from lamina I tract neurons via the
      ventromedial posterior nucleus of the thalamus. (7) The transmission of activity
      from visceral afferents to second-order neurons in spinal cord is modulated in an
      excitatory and inhibitory way by endogenous anti- and pronociceptive control
      systems in the lower and upper brain stem. These control systems are under
      cortical control. (8) Visceral pain is referred to deep somatic tissues, to the
      skin and to other visceral organs. This referred pain consists of spontaneous
      pain and mechanical hyperalgesia. The mechanisms underlying referred pain and the
      accompanying tissue changes have been little explored. 

PMID- 24903038
TI  - [Psychophysiology of visceral pain].
AB  - The psychophysiology of visceral pain is--different from cardiac psychophysiology
      -much less well investigated due to the invasiveness of its methods and problems
      associated with reliably and reproducibly stimulating as well as recording of the
      gastrointestinal tract. Despite these problems, the last 30 years have documented
      a number of psychophysiological phenomena such as the perception (interoception)
      of visceral stimuli, the effect of emotions and stress on visceral sensations,
      and the effect of visceral processes on cortical processing. This was mainly due
      to the application of neurophysiological techniques (cortical imaging and
      stimulation) in these investigations.

PMID- 24903039
TI  - [Prevalence of disabling abdominal pain and menstrual cramp. Results from a
      representative survey of the general German population].
AB  - BACKGROUND: There are no data available on the prevalence of disabling abdominal
      pain and menstrual cramp in adults in Germany. METHODS: Abdominal pain and
      menstrual cramp, additional somatic symptoms and depressive symptoms were
      assessed by the Patient Health Questionnaires (PHQ) 15 and 9 in persons >= 14
      years from a sample representative of the general German population. The
      association of disabling abdominal and menstrual cramp with demographic and
      clinical variables was tested by logistic regression analyses. RESULTS: A total
      of 2524 out of 4064 (62.1 %) contacted persons participated in the study. Of the
      participants 11.9 % reported suffering from slight abdominal pain and 0.9 %
      reported suffering from severe abdominal pain within the last 4 weeks. Female
      gender with an odds ratio (OR) of 2.23 (95 % confidence interval CI 1.67-2.98, p
      < 0.001), younger age (OR 0.97, 95 % CI 0.96-0.98, p < 0.001), physical symptom
      burden PHQ 15 (OR 1.33, 95 % CI 1.26-1.40, p < 0.0001) and depression PHQ 9 (OR
      1.13, 95 % CI 1.08-1.77, p < 0.0001) were predictive for abdominal pain. Of the
      women aged 14-55 years 19.8 % reported to be slightly troubled by menstrual cramp
      and 3.9 % reported suffering from severe menstrual cramp within the last 4 weeks.
      Menstrual cramps were predicted by younger age (OR 0.96, 95 % CI 0.94-0.97, p <
      0.001), somatic symptom burden PHQ 15 (OR 1.24, 1.12-1.36, p < 0.0001) and
      depression PHQ 9 (OR 1.08, 95 % CI 1.01-1.15, p < 0.0001). CONCLUSION: Persons in
      the general German population frequently reported slightly disabling abdominal
      pain and menstrual cramp; however, severely disabling abdominal pain and
      menstrual cramp were rarely reported. Abdominal pain and menstrual cramps were
      associated with additional somatic complaints and depression.

PMID- 24903041
TI  - [Chronic chest pain].
AB  - BACKGROUND: Chest pain is a symptom commonly reported by persons in the general
      population and represents a differential diagnostic challenge. MATERIAL AND
      METHODS: The paper is based on a narrative review with a selective search of the
      literature in Medline for reviews and guidelines on the prevalence and treatment
      of non-malignant diseases with chronic chest pain in gastroenterology, gynecology
      and cardiology. RESULTS: The prevalence and current treatment recommendations for
      the different forms of gastroesophageal reflux disease (GERD), erosive and non
      erosive types and irritable esophagus, non-cardiac chest pain, refractory angina
      in coronary heart disease and postmastectomy nand poststernotomy syndromes are
      presented. In cases of failure of the established therapy of a single medical
      discipline, an interdisciplinary assessment including psychosocial issues is
      recommended. Evidence-based guidelines are available for the management of GERD
      and of refractory angina. Treatment of postmastectomy and poststernotomy
      syndromes is based on case reports and expert opinion. CONCLUSION: There is a
      need for controlled studies on the symptomatic treatment of pain in irritable
      esophagus, non-cardiac chest pain, postmastectomy and poststernotomy syndromes.

PMID- 24903040
TI  - [Perioperative pain management for abdominal and thoracic surgery].
AB  - Abdominal and thoracic surgical procedures can result in significant acute
      postoperative pain. Present evidence shows that postoperative pain management
      remains inadequate especially after "minor" surgical procedures. Various
      therapeutic options including regional anesthesia techniques and systemic
      pharmacotherapy are available for effective treatment of postoperative pain. This
      work summarizes the pathophysiological background of postoperative pain after
      abdominal and thoracic surgery and discusses the indication, effectiveness,
      risks, and benefits of the different therapeutic options. Special focus is given
      to the controversial debate about the indication for epidural analgesia, as well
      as various alternative therapeutic options, including transversus abdominis plane
      (TAP) block, paravertebral block (PVB), wound infiltration with local
      anesthetics, and intravenous lidocaine. In additional, indications and
      contraindications of nonopioid analgesics after abdominal and thoracic surgery
      are discussed and recommendations based on scientific evidence and individual
      risk and benefit analysis are made. All therapeutic options discussed are
      eligible for clinical use and may contribute to improve postoperative pain
      outcome after abdominal and thoracic surgical procedures. 

PMID- 24903042
TI  - [Pain therapy in irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is one of the most common gastrointestinal
      diseases. It is characterized by chronic abdominal pain, typically associated
      with altered bowel habits that cannot be explained by structural abnormalities in
      routine diagnostic workup. Based on the predominant symptom, IBS can be divided
      into different subtypes: IBS with predominant constipation, diarrhea, bloating,
      or pain. Knowledge about the complex and multifactorial IBS pathophysiology has
      increased tremendously in recent years, e.g., IBS may be related to alterations
      in gastrointestinal motility, visceral sensitivity, and the mucosal immune
      system. It is important, both for the patient and the physician, that IBS
      diagnosis is made quickly and thoroughly based on the typical symptom complex and
      exclusion of relevant differential diagnoses and to reassure the patient that IBS
      is a chronic, but benign disease. These components are the fundamental basis for
      a good patient-physician relationship and for a successful long-term management
      of this potentially very compromising disorder. IBS therapy is based on general
      measures as well as symptom-oriented medical therapy, where improvement of
      abdominal pain is one of the main goals in treating IBS patients. Several pain
      treatment options are available, which may be used long-term or on demand and
      which may be combined with other therapies. General medical approaches include
      antispasmodics, improvement of bowel function, phytotherapy, and probiotics.
      Especially in patients with psychological comorbidities, antidepressants may be
      used. Modern drug treatments include the GC-C agonist linaclotide in IBS with
      predominant constipation, the locally acting antibiotic rifaximin in IBS with
      bloating, and 5-HT3 antagonists in IBS with predominant diarrhea. Psychotherapy
      should be included in an interdisciplinary approach in refractory cases or in
      psychological comorbidity. 

PMID- 24903043
TI  - [Pain management in chronic pancreatitis and chronic inflammatory bowel
      diseases].
AB  - Apart from local inflammation and defects in secretion, central mechanisms are
      important for pain etiology in chronic pancreatitis. Therefore, centrally acting
      co-analgetic agents can be used in addition to classical pain medications.
      Endoscopic interventions are preferred in patients with obvious dilation of the
      pancreatic duct. Surgical interventions are generally more effective although
      they are usually reserved for patients with prior failure of conservative
      treatment. Diverse surgical options with different efficacies and morbidities are
      used in individual patients.One of the main problems in chronic inflammatory
      bowel diseases is abdominal pain. Primarily the underlying disease needs to be
      adequately treated. Symptomatic pain management will most likely include
      treatment with acetaminophen and tramadol as well as occasionally principles of a
      multimodal pain regimen. For the treatment of arthralgia as well as enteropathy
      associated arthritis the same treatment options are available as for other
      spondyloarthritic disorders. 

PMID- 24903044
TI  - [Chronic pelvic pain in women].
AB  - BACKGROUND: Chronic pelvic pain in women represents a difficult diagnostic and
      therapeutic problem in the gynecological practice which is always a challenge
      when dealing with affected women. GYNECOLOGICAL CAUSES: Possible gynecological
      causes are endometriosis, adhesions and/or pelvic inflammatory disease (PID),
      pelvic varicosis and ovarian retention syndrome/ovarian remnant syndrome. Other
      somatic causes are irritable bowel syndrome, bladder pain syndrome, interstitial
      cystitis and fibromyalgia. PSYCHOSOCIAL FACTORS: Psychosocial causes contributing
      to chronic pelvic pain are a high comorbidity with psychological factors, such as
      anxiety disorders and substance abuse or depression but the influence of social
      factors is less certain. The association with physical and sexual abuse also
      remains unclear. DIAGNOSTICS AND THERAPY: Important diagnostic steps are
      recording the patient history, a gynecological examination and laparoscopy.
      Multidisciplinary therapeutic approaches are considered to be very promising.
      Basic psychosomatic care and psychotherapy should be integrated into the
      therapeutic concept at an early stage.

PMID- 24903045
TI  - [Chronic pelvic pain].
AB  - BACKGROUND: Chronic pelvic pain represents a multifactorial problem of unknown
      etiology. International standardized diagnostic and therapeutic approaches do not
      exist. METHODS: Medline and PubMed databases were searched for systematic reviews
      and guidelines for prevalence and therapy of chronic pelvic pain syndrome.
      RESULTS: Frequency, clinical picture, and treatment concepts for various forms of
      chronic pelvic pain are presented. If established treatments fail, then
      multimodal therapy concepts are recommended. Controlled studies, which fulfill
      evidence-based medicine criteria, are lacking. CONCLUSION: The success of
      multimodal therapeutic approaches in other chronic pain diseases should lead to
      the development and verification of these for chronic pelvic pain.

PMID- 24903047
TI  - Effect of lignin chemistry on the enzymatic hydrolysis of woody biomass.
AB  - The impact of lignin-derived inhibition on enzymatic hydrolysis is investigated
      by using lignins isolated from untreated woods and pretreated wood pulps. A new
      method, biomass reconstruction, for which isolated lignins are precipitated onto
      bleached pulps to mimic lignocellulosic biomass, is introduced, for the first
      time, to decouple the lignin distribution issue from lignin chemistry. Isolated
      lignins are physically mixed and reconstructed with bleached pulps. Lignins
      obtained from pretreated woods adsorb two to six times more cellulase than
      lignins obtained from untreated woods. The higher adsorption of enzymes on lignin
      correlates with decreased carbohydrate conversion in enzymatic hydrolysis. In
      addition, the reconstructed softwood substrate has a lower carbohydrate
      conversion than the reconstructed hardwood substrate. The degree of condensation
      of lignin increases significantly after pretreatment, especially with softwood
      lignins. In this study, the degree of condensation of lignin (0.02 to 0.64) and
      total OH groups in lignin (1.7 to 1.1) have a critical impact on cellulase
      adsorption (9 to 70%) and enzymatic hydrolysis (83.2 to 58.2%); this may provide
      insights into the more recalcitrant nature of softwood substrates.

PMID- 24903046
TI  - [Complex regional pain syndrome: A current review].
AB  - Complex regional pain syndrome (CRPS) may develop following fractures, limb
      trauma, or lesions of the peripheral or central nervous system. The clinical
      picture consists of a triad of symptoms including autonomic, sensory, and motor
      dysfunction. Diagnosis is based on clinical signs and symptoms according to the
      Budapest criteria. Therapy is based on an individual and multidisciplinary
      approach. Distinct methods of physical therapy and pharmacological strategies are
      the mainstay of therapy. Pharmacotherapy is based on individual symptoms and
      includes steroids, free radical scavengers, treatment of neuropathic pain, and
      agents interfering with bone metabolism. In some cases invasive methods may be
      considered. 

PMID- 24903050
TI  - The EFIS-EJI Ruggero Ceppellini Advanced School of Immunology: Malaria,
      Tuberculosis and HIV/AIDS: novel vaccination strategies against the three major
      killers.

PMID- 24903048
TI  - Miscibility as a factor for component crystallization in multisolute frozen
      solutions.
AB  - The relationship between the miscibility of formulation ingredients and their
      crystallization during the freezing segment of the lyophilization process was
      studied. The thermal properties of frozen solutions containing myo-inositol and
      cosolutes were obtained by performing heating scans from -70  degrees C before
      and after heat treatment at -20  degrees C to -5  degrees C. Addition of dextran
      40,000 reduced and prevented crystallization of myo-inositol. In the first scan,
      some frozen solutions containing an inositol-rich mixture with dextran showed
      single broad transitions (Tg's: transition temperatures of maximally freeze
      concentrated solutes) that indicated incomplete mixing of the concentrated
      amorphous solutes. Heat treatment of these frozen solutions induced separation of
      the solutes into inositol-dominant and solute mixture phases (Tg' splitting)
      following crystallization of myo-inositol (Tg' shifting). The crystal growth
      involved myo-inositol molecules in the solute mixture phase. The amorphous
      amorphous phase separation and resulting loss of the heteromolecular interaction
      in the freeze-concentrated inositol-dominant phase should allow ordered assembly
      of the solute molecules required for nucleation. Some dextran-rich and
      intermediate concentration ratio frozen solutions retained single Tg's of the
      amorphous solute mixture, both before and after heat treatments. The relevance of
      solute miscibility on the crystallization of myo-inositol was also indicated in
      the systems containing glucose or recombinant human albumin.

PMID- 24903057
TI  - Patches of hair loss on the occipital scalp.

PMID- 24903056
TI  - The effects of Medieval dams on genetic divergence and demographic history in
      brown trout populations.
AB  - BACKGROUND: Habitat fragmentation has accelerated within the last century, but
      may have been ongoing over longer time scales. We analyzed the timing and genetic
      consequences of fragmentation in two isolated lake-dwelling brown trout
      populations. They are from the same river system (the Gudena River, Denmark) and
      have been isolated from downstream anadromous trout by dams established ca. 600
      800 years ago. For reference, we included ten other anadromous populations and
      two hatchery strains. Based on analysis of 44 microsatellite loci we investigated
      if the lake populations have been naturally genetically differentiated from
      anadromous trout for thousands of years, or have diverged recently due to the
      establishment of dams. RESULTS: Divergence time estimates were based on 1)
      Approximate Bayesian Computation and 2) a coalescent-based isolation-with-gene
      flow model. Both methods suggested divergence times ca. 600-800 years bp,
      providing strong evidence for establishment of dams in the Medieval as the factor
      causing divergence. Bayesian cluster analysis showed influence of stocked trout
      in several reference populations, but not in the focal lake and anadromous
      populations. Estimates of effective population size using a linkage
      disequilibrium method ranged from 244 to > 1,000 in all but one anadromous
      population, but were lower (153 and 252) in the lake populations. CONCLUSIONS: We
      show that genetic divergence of lake-dwelling trout in two Danish lakes reflects
      establishment of water mills and impassable dams ca. 600-800 years ago rather
      than a natural genetic population structure. Although effective population sizes
      of the two lake populations are not critically low they may ultimately limit
      response to selection and thereby future adaptation. Our results demonstrate that
      populations may have been affected by anthropogenic disturbance over longer time
      scales than normally assumed.

PMID- 24903058
TI  - A new human leukocyte antigen-A allele, HLA-A*02:482.

PMID- 24903055
TI  - Bidirectional regulation of angiogenesis and miR-18a expression by PNS in the
      mouse model of tumor complicated by myocardial ischemia.
AB  - BACKGROUND: Panax Notoginseng Saponins (PNS) is the major class of active
      constituents of notoginseng, a natural product extensively used as a therapeutic
      agent in China. Tumor when accompanied by cardiovascular disorders poses a
      greater challenge for clinical management given the paradoxical involvement of
      angiogenesis, therefore gaining increased research attention. This study aim to
      investigate effects of PNS and its activity components in the mouse model of
      tumor complicated with myocardial ischemia. METHODS: Tumor complexed with
      myocardial ischemia mouse model was first established, which was followed by
      histological and immunohistochemistry examination to assess the effect of
      indicated treatments on tumor, myocardial ischemia and tissue specific
      angiogenesis. MicroRNA (miRNA) profiling was further carried out to identify
      potential miRNA regulators that might mechanistically underline the therapeutic
      effects of PNS in this complex model. RESULTS: PNS and its major activity
      components Rg1, Rb1 and R1 suppressed tumor growth and simultaneously attenuated
      myocardial ischemia. PNS treatment led to decreased expression of CD34 and vWF in
      tumor and increased expression of these vascular markers in heart. PNS treatment
      resulted in reduced expression of miR-18a in tumor and upregulated expression of
      miR-18a in heart. CONCLUSIONS: Our data demonstrated for the first time that PNS
      exerts tissue specific regulatory effects on angiogenesis in part through
      modulating the expression of miR-18a, which could be responsible for its
      bidirectional effect on complex disease conditions where paradoxical angiogenesis
      is implicated. Therefore, our study provides experimental evidence warranting
      evaluation of PNS and related bioactive component as a rational therapy for
      complex disease conditions including co-manifestation of cancer and ischemic
      cardiovascular disease.

PMID- 24903059
TI  - A re-evaluation of how functional groups modify the electronic structure of
      graphene oxide.
AB  - The first 4 eV of the conduction band in graphene oxide is dominated by states
      from carbon sites that are in close proximity, but not directly bonded, to
      oxidizing functional groups. The carbon sites that are bonded directly to these
      groups, such as epoxide and hydroxyl groups, are much higher in energy. 

PMID- 24903060
TI  - Correlation between architectural variables and torque in the erector spinae
      muscle during maximal isometric contraction.
AB  - This study analysed whether a significant relationship exists between the torque
      and muscle thickness and pennation angle of the erector spinae muscle during a
      maximal isometric lumbar extension with the lumbar spine in neutral position.
      This was a cross-sectional study in which 46 healthy adults performed three
      repetitions for 5 s of maximal isometric lumbar extension with rests of 90 s.
      During the lumbar extensions, bilateral ultrasound images of the erector spinae
      muscle (to measure pennation angle and muscle thickness) and torque were
      acquired. Reliability test analysis calculating the internal consistency
      (Cronbach's alpha) of the measure, correlation between pennation angle, muscle
      thickness and torque extensions were examined. Through a linear regression the
      contribution of each independent variable (muscle thickness and pennation angle)
      to the variation of the dependent variable (torque) was calculated. The results
      of the reliability test were: 0.976-0.979 (pennation angle), 0.980-0.980 (muscle
      thickness) and 0.994 (torque). The results show that pennation angle and muscle
      thickness were significantly related to each other with a range between 0.295 and
      0.762. In addition, multiple regression analysis showed that the two variables
      considered in this study explained 68% of the variance in the torque. Pennation
      angle and muscle thickness have a moderate impact on the variance exerted on the
      torque during a maximal isometric lumbar extension with the lumbar spine in
      neutral position.

PMID- 24903061
TI  - Spatiotemporal clusters of malaria cases at village level, northwest Ethiopia.
AB  - BACKGROUND: Malaria attacks are not evenly distributed in space and time. In
      highland areas with low endemicity, malaria transmission is highly variable and
      malaria acquisition risk for individuals is unevenly distributed even within a
      neighbourhood. Characterizing the spatiotemporal distribution of malaria cases in
      high-altitude villages is necessary to prioritize the risk areas and facilitate
      interventions. METHODS: Spatial scan statistics using the Bernoulli method were
      employed to identify spatial and temporal clusters of malaria in high-altitude
      villages. Daily malaria data were collected, using a passive surveillance system,
      from patients visiting local health facilities. Georeference data were collected
      at villages using hand-held global positioning system devices and linked to
      patient data. Bernoulli model using Bayesian approaches and Marcov Chain Monte
      Carlo (MCMC) methods were used to identify the effects of factors on spatial
      clusters of malaria cases. The deviance information criterion (DIC) was used to
      assess the goodness-of-fit of the different models. The smaller the DIC, the
      better the model fit. RESULTS: Malaria cases were clustered in both space and
      time in high-altitude villages. Spatial scan statistics identified a total of 56
      spatial clusters of malaria in high-altitude villages. Of these, 39 were the most
      likely clusters (LLR = 15.62, p < 0.00001) and 17 were secondary clusters (LLR =
      7.05, p < 0.03). The significant most likely temporal malaria clusters were
      detected between August and December (LLR = 17.87, p < 0.001). Travel away home,
      males and age above 15 years had statistically significant effect on malaria
      clusters at high-altitude villages. CONCLUSION: The study identified spatial
      clusters of malaria cases occurring at high elevation villages within the
      district. A patient who travelled away from home to a malaria-endemic area might
      be the most probable source of malaria infection in a high-altitude village.
      Malaria interventions in high altitude villages should address factors associated
      with malaria clustering.

PMID- 24903062
TI  - Efficacy of baby-CIMT: study protocol for a randomised controlled trial on
      infants below age 12 months, with clinical signs of unilateral CP.
AB  - BACKGROUND: Infants with unilateral brain lesions are at high risk of developing
      unilateral cerebral palsy (CP). Given the great plasticity of the young brain,
      possible interventions for infants at risk of unilateral CP deserve exploration.
      Constraint-induced movement therapy (CIMT) is known to be effective for older
      children with unilateral CP but is not systematically used for infants. The
      development of CIMT for infants (baby-CIMT) is described here, as is the
      methodology of an RCT comparing the effects on manual ability development of baby
      CIMT versus baby-massage. The main hypothesis is that infants receiving baby-CIMT
      will develop manual ability in the involved hand faster than will infants
      receiving baby-massage in the first year of life. METHOD AND DESIGN: The study
      will be a randomised, controlled, prospective parallel-group trial. Invited
      infants will be to be randomised to either the baby-CIMT or the baby-massage
      group if they: 1) are at risk of developing unilateral CP due to a known neonatal
      event affecting the brain or 2) have been referred to Astrid Lindgren Children's
      Hospital due to asymmetric hand function. The inclusion criteria are age 3-8
      months and established asymmetric hand use. Infants in both groups will receive
      two 6-weeks training periods separated by a 6-week pause, for 12 weeks in total
      of treatment. The primary outcome measure will be the new Hand Assessment for
      Infants (HAI) for evaluating manual ability. In addition, the Parenting Sense of
      Competence scale and Alberta Infant Motor Scale will be used. Clinical
      neuroimaging will be utilized to characterise the brain lesion type. To compare
      outcomes between treatment groups generalised linear models will be used.
      DISCUSSION: The model of early intensive intervention for hand function, baby
      CIMT evaluated by the Hand Assessment for Infants (HAI) will have the potential
      to significantly increase our understanding of how early intervention of upper
      limb function in infants at risk of developing unilateral CP can be performed and
      measured. TRIAL REGISTRATION: SFO-V4072/2012, 05/22/2013.

PMID- 24903063
TI  - BU08073 a buprenorphine analogue with partial agonist activity at MU-receptors in
      vitro but long-lasting opioid antagonist activity in vivo in mice.
AB  - BACKGROUND AND PURPOSE: Buprenorphine is a potent analgesic with high affinity at
      MU, delta and kappa and moderate affinity at nociceptin opioid (NOP) receptors.
      Nevertheless, NOP receptor activation modulates the in vivo activity of
      buprenorphine. Structure activity studies were conducted to design buprenorphine
      analogues with high affinity at each of these receptors and to characterize them
      in in vitro and in vivo assays. EXPERIMENTAL APPROACH: Compounds were tested for
      binding affinity and functional activity using [(35) S]GTPgammaS binding at each
      receptor and a whole-cell fluorescent assay at MU receptors. BU08073 was
      evaluated for antinociceptive agonist and antagonist activity and for its effects
      on anxiety in mice. KEY RESULTS: BU08073 bound with high affinity to all opioid
      receptors. It had virtually no efficacy at delta, kappa and NOP receptors,
      whereas at MU receptors, BU08073 has similar efficacy as buprenorphine in both
      functional assays. Alone, BU08073 has anxiogenic activity and produces very
      little antinociception. However, BU08073 blocks morphine and U50,488-mediated
      antinociception. This blockade was not evident at 1 h post-treatment, but is
      present at 6 h and remains for up to 3-6 days. CONCLUSIONS AND IMPLICATIONS:
      These studies provide structural requirements for synthesis of 'universal' opioid
      ligands. BU08073 had high affinity for all the opioid receptors, with moderate
      efficacy at MU receptors and reduced efficacy at NOP receptors, a profile
      suggesting potential analgesic activity. However, in vivo, BU08073 had long
      lasting antagonist activity, indicating that its pharmacokinetics determined both
      the time course of its effects and what receptor-mediated effects were observed.
      LINKED ARTICLES: This article is part of a themed section on Opioids: New
      Pathways to Functional Selectivity. To view the other articles in this section
      visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24903064
TI  - Catheter ablation of asymptomatic longstanding persistent atrial fibrillation:
      impact on quality of life, exercise performance, arrhythmia perception, and
      arrhythmia-free survival.
AB  - BACKGROUND: Impact of catheter ablation on exercise performance, quality of life
      (QoL) and symptom perception in asymptomatic longstanding persistent AF (LSP-AF)
      patients has not been reported yet. METHODS AND RESULTS: Sixty-one consecutive
      patients (mean age 62 +/-13 years, 71% males) with asymptomatic LSP-AF undergoing
      first catheter ablation were enrolled. Extended pulmonary vein antrum isolation
      plus ablation of complex fractionated atrial electrograms and nonpulmonary vein
      triggers was performed in all. QoL survey was taken at baseline and 12-months
      postablation, using Short Form-36 (SF-36). Information on arrhythmia perception
      was obtained using a standard questionnaire and corroborating symptoms with
      documented evidence of arrhythmia. Exercise tests were performed on 38 patients
      at baseline and 5 months after procedure. Recurrence was assessed using event
      recorder, cardiology evaluation, electrocardiogram, and 7-day holter monitoring.
      After 20 +/- 5 months follow-up, 36 (57%) patients remained recurrence-free off
      AAD. Of the 25 patients experiencing recurrence, 21 (84%) were symptomatic.
      Compared to baseline, follow-up SF-36 scores improved significantly in many
      measures. For patients with successful ablation, physical component summary (PCS)
      and mental component summary (MCS) demonstrated substantial improvement ( MCS:
      64.2 +/- 22.3 to 70.1 +/- 18.6 [P = 0.041]; PCS: 62.6 +/- 18.4 to 70.0 +/- 14.4
      [P = 0.032]). Postablation exercise study in recurrence-free patients showed
      significant reduction in resting and peak heart rate (75 +/- 11 vs. 90 +/- 17 and
      132 +/- 20 vs. 154.5 +/- 36, respectively, P < 0.001), increase in peak oxygen
      pulse (13.4 +/- 3 vs. 18.9 +/- 16 mL/beat, Delta5.5 +/- 15, P = 0.001), peak VO2
      /kg (19.7 +/- 5 to 23.4 +/- 13 mL/kg/min [Delta 3.7 +/- 10, P = 0.043]), and
      corresponding MET (5.6 +/- 1 to 6.7 +/- 4 [Delta1.1 +/- 3, P = 0.03]). No
      improvement was observed in patients with failed procedures. CONCLUSION:
      Successful ablation improves exercise performance and QoL in asymptomatic LSP-AF
      patients.

PMID- 24903065
TI  - Mode of delivery changes oxidative and antioxidative properties of human milk: a
      prospective controlled clinical investigation.
AB  - OBJECTIVE: To evaluate the influence of delivery mode on oxidative stress in
      human breast milk. METHODS: Thirty-three women who delivered by vaginal birth and
      55 women who underwent cesarean section (CS) were included in this study.
      Colostral samples were collected on the second day after delivery. Total
      antioxidative status (TAS), total oxidative status (TOS), oxidative stress index
      (OSI), malonyldialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were
      determined and compared. RESULTS: Colostrum TAS was significantly higher in women
      of vaginal birth, than in women with CS (p < 0.001). Milk TOS and OSI were found
      to be significantly increased in women with CS under general anesthesia. A marked
      increase in colostral GSH-Px levels after vaginal delivery was also noticed (p <
      0.001). CONCLUSION: This study revealed that vaginal birth is associated with
      decreased oxidative stress in colostrum than CS, which suggest that mode of
      delivery plays an important role in the antioxidative production of breast milk.

PMID- 24903066
TI  - Detection and quantification of human herpes viruses types 4-6 in sperm samples
      of patients with fertility disorders and chronic inflammatory urogenital tract
      diseases.
AB  - Acute and chronic infections of the seminal tract are among the most common
      causes of male infertility. As at least half of male infertility cases are
      classified as idiopathic, some of these cases might be attributed to asymptomatic
      infection. The detection and quantification of Epstein-Barr virus (EBV),
      cytomegalovirus (CMV) and human herpes virus type 6 (HHV-6) DNA in semen samples
      were performed. A total of 232 patients were divided into five groups: (i)
      infertile men with varicocoele; (ii) men with idiopathic infertility; (iii)
      infertile men with chronic inflammatory urogenital tract diseases (IUTD); (iv)
      fertile men with IUTD and (v) men whose partners had a history of pregnancy loss.
      In the study population, the prevalence of viral DNA was 17.7, 3.4% for EBV, 5.2%
      for CMV, 6.5% for HHV-6, 0.43% for EBV + CMV, 0.87% for EBV + HHV-6 and 1.3% for
      CMV + HHV-6. The median viral loads for EBV, CMV and HHV-6 were 500, 2250 and 250
      copies/mL respectively. Of the sperm cell fractions, derived from infected
      samples 87.5% contained viral DNA. No association between EBV and fertility
      disorders or IUTD was found. CMV detection was much higher in the group of
      patients with infertility and concomitant IUTD compared with the other groups
      combined (18.5% vs. 5.4%, p = 0.03) and associated with reduced sperm cell count
      (39.5 * 10(6) /mL vs. 72.5 * 10(6) /mL, p = 0.036). Immunostaining of spermatozoa
      from infected samples and in vitro-infected cells detected CMV in sperm heads,
      tails and connecting pieces and revealed attachment to sperm membrane and
      intracellular localization. HHV-6 was the more common in fertile men with chronic
      IUTD than in the other groups combined (19% vs. 6.3%, p = 0.018) and had no
      effect on sperm parameters. The results suggest that both CMV and HHV-6 may
      contribute to the aetiology of IUTD and, moreover, CMV-associated IUTD can lead
      to male sterility.

PMID- 24903067
TI  - The relationship between reductions in knee loading and immediate pain response
      whilst wearing lateral wedged insoles in knee osteoarthritis.
AB  - Studies of lateral wedge insoles (LWIs) in medial knee osteoarthritis (OA) have
      shown reductions in the average external knee adduction moment (EKAM) but no
      lessening of knee pain. Some treated patients actually experience increases in
      the EKAM which could explain the overall absence of pain response. We examined
      whether, in patients with painful medial OA, reductions in the EKAM were
      associated with lessening of knee pain. Each patient underwent gait analysis
      whilst walking in a control shoe and two LWI's. We evaluated the relationship
      between change in EKAM and change in knee pain using Spearman Rank Correlation
      coefficients and tested whether dichotomizing patients into biomechanical
      responders (decreased EKAM) and non-responders (increased EKAM) would identify
      those with reductions in knee pain. In 70 patients studied, the EKAM was reduced
      in both LWIs versus control shoe (-5.21% and -6.29% for typical and supported
      wedges, respectively). The change in EKAM using LWIs was not significantly
      associated with the direction of knee pain change. Further, 54% were
      biomechanical responders, but these persons did not have more knee pain reduction
      than non-responders. Whilst LWIs reduce EKAM, there is no clearcut relationship
      between change in medial load when wearing LWIs and corresponding change in knee
      pain.

PMID- 24903069
TI  - The wells of Pompeii.

PMID- 24903070
TI  - Three-year outcomes of recovery of erectile function after open radical
      prostatectomy with sural nerve grafting.
AB  - INTRODUCTION: Optimal oncologic control of higher stage prostate cancers often
      requires sacrificing the neurovascular bundles (NVB) with subsequent
      postoperative erectile dysfunction (ED), which can be treated with interposition
      graft using sural nerve. AIMS: To examine the long term outcome of sural nerve
      grafting (SNG) during radical retropubic prostatectomy (RRP) performed by a
      single surgeon. METHODS: Sixty-six patients with clinically localized prostate
      cancer and preoperative International Index of Erectile Function (IIEF) score >20
      who underwent RRP were included. NVB excision was performed if the risk of side
      specific extra-capsular extension (ECE) was >25% on Ohori' nomogram. SNG was
      harvested by a plastic surgeon, contemporaneously as the urologic surgeon was
      performing RRP. IIEF questionnaire was used pre- and postoperatively and at
      follow-up. MAIN OUTCOME MEASURES: Postoperative IIEF score at three years of men
      undergoing RRP with SNG. Recovery of potency was defined as postoperative IIEF-EF
      domain score >22. RESULTS: There were 43 (65%) unilateral SNG and 23 (35%)
      bilateral SNG. Mean surgical time was 164 minutes (71 to 221 minutes).The mean
      preoperative IIEF score was 23.4+1.6. With a mean follow-up of 35 months, 19
      (28.8%) patients had IIEF score >22. The IIEF-EF scores for those who had
      unilateral SNG and bilateral SNG were 12.9+4.9 and 14.8+5.3 respectively. History
      of diabetes (P=0.001) and age (P=0.007) negatively correlated with recovery of
      EF. 60% patients used PDE5i and showed a significantly higher EF recovery (43%
      vs. 17%, P=0.009). CONCLUSIONS: SNG can potentially improve EF recovery for
      potent men with higher stage prostate cancer undergoing RP. The contemporaneous,
      multidisciplinary approach provides a good quality graft and expedited the
      procedure without interrupting the work-flow.

PMID- 24903071
TI  - Increased level of acute phase reactants in patients infected with modern
      Mycobacterium tuberculosis genotypes in Mwanza, Tanzania.
AB  - BACKGROUND: There is increasing evidence to suggest that different Mycobacterium
      tuberculosis lineages cause variations in the clinical presentation of
      tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to
      be more likely to cause active TB in human populations from a distinct genetic
      ancestry. This study describes the genetic biodiversity of M. tuberculosis
      genotypes in Mwanza city, Tanzania and the clinical presentation of the disease
      caused by isolates of different lineages. METHODS: Two-hundred-fifty-two isolates
      from pulmonary TB patients in Mwanza, Tanzania were characterized by
      spoligotyping, and 45 isolates were further characterized by mycobacterium
      interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The
      patients' level of the acute phase reactants AGP, CRP and neutrophil counts, in
      addition to BMI, were measured and compared to the M. tuberculosis lineage of the
      infectious agent for each patient. RESULTS: The most frequent genotype was ST59
      (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE,
      followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of
      diversity (15.7% [39 different ST's out of 248 isolates]) of genotypes, in
      addition to a high level of mixed M. tuberculosis sub-populations among isolates
      with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and
      isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed.
      Isolates of the 'modern' (TbD1-) Euro-American lineage induced higher levels of
      alpha1-acid glycoprotein (beta = 0.4, P = 0.02; 95% CI [0.06-0.66]) and
      neutrophil counts (beta = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI
      score (beta = -1.0, P = 0.04; 95% CI[-1.89 - (-0.03)]). LAM11_ZWE ('modern')
      isolates induced higher levels of CRP (beta = 24.4, P = 0.05; 95% CI[0.24-48.63])
      and neutrophil counts (beta = 0.9, P = 0.03; 95% CI[0.09-1.70]). CONCLUSION: The
      low diversity of genotypes may be explained by an evolutionary advantage of the
      most common lineages over other lineages combined with optimal conditions for
      transmission, such as overcrowding and inadequate ventilation. The induction of
      higher levels of acute phase reactants in patients infected by 'modern' lineage
      isolates compared to 'ancient' lineages may suggest increased virulence among
      'modern' lineage isolates.

PMID- 24903068
TI  - Bacterial community shift is induced by dynamic environmental parameters in a
      changing coastal ecosystem (northern Adriatic, northeastern Mediterranean Sea)--a
      2-year time-series study.
AB  - The potential link between the microbial dynamics and the environmental
      parameters was investigated in a semi-enclosed and highly dynamic coastal system
      (Gulf of Trieste, northern Adriatic Sea, NE Mediterranean Sea). Our comprehensive
      2-year time-series study showed that despite the shallowness of this area, there
      was a significant difference between the surface and the bottom bacterial
      community structure. The bottom bacterial community was more diverse than the
      surface one and influenced by sediment re-suspension. The surface seawater
      temperature had a profound effect on bacterial productivity, while the bacterial
      community structure was more affected by freshwater-borne nutrients and
      phytoplankton blooms. Phytoplankton blooms caused an increase of
      Gammaproteobacteria (Alteromonadaceae, SAR86 and Vibrionaceae) and shift in
      dominance from SAR11 to Rhodobacteraceae taxon at the surface. Our results
      propose the importance of the water mass movements as drivers of freshwater-borne
      nutrients and of allochthonous microbial taxa. This study emphasizes the
      prediction power based on association networks analyses that are fed with long
      term measurements of microbial and environmental parameters. These interaction
      maps offer valuable insights into the response of marine ecosystem to climate-
      and anthropogenic-driven stressors. 

PMID- 24903072
TI  - Stability of a 1.0 mg ml(-1) aqueous pholcodine solution for allergy skin
      testing.

PMID- 24903073
TI  - IDH1 mutation is associated with seizures and protoplasmic subtype in patients
      with low-grade gliomas.
AB  - OBJECTIVE: The isocitrate dehydrogenase 1 (IDH1) R132H mutation is the most
      common mutation in World Health Organization (WHO) grade II gliomas, reported to
      be expressed in 70-80%, but only 5-10% of high grade gliomas. Low grade tumors,
      especially the protoplasmic subtype, have the highest incidence of tumor
      associated epilepsy (TAE). The IDH1 mutation leads to the accumulation of 2
      hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to
      glutamate, an excitatory neurotransmitter that has been implicated in the
      pathogenesis of TAE. We hypothesized that expression of mutated IDH1 may play a
      role in the pathogenesis of TAE in low grade gliomas. METHODS: Thirty consecutive
      patients with WHO grade II gliomas were analyzed for the presence of the IDH1
      R132H mutation using immunohistochemistry. The expression of IDH1 mutation was
      semiquantified using open-source biologic-imaging analysis software. RESULTS: The
      percentage of cells positive for the IDH1-R132H mutation was found to be higher
      in patients with TAE compared to those without TAE (median and interquartile
      range (IQR) 25.3% [8.6-53.5] vs. 5.2% [0.6-13.4], p = 0.03). In addition, we
      found a significantly higher median IDH1 mutation expression level in the
      protoplasmic subtype of low grade glioma (52.2% [IQR 19.9-58.6] vs. 13.8% [IQR
      3.9-29.4], p = 0.04). SIGNIFICANCE: Increased expression of the IDH1-R132H
      mutation is associated with seizures in low grade gliomas and also with the
      protoplasmic subtype. This supports the hypothesis that this mutation may play a
      role in the pathogenesis of both TAE and low grade gliomas.

PMID- 24903074
TI  - miR-27 inhibits adipocyte differentiation via suppressing CREB expression.
AB  - miR-27 plays a negative role in the regulation of adipogenesis. However, the
      molecular mechanism still remains to be clarified. In the present study, we found
      that miR-27 inhibits adipogenesis partially by repressing the early adipogenic
      transcription factor cAMP response element-binding protein by directly targeting
      its 3' untranslated region. In addition, we demonstrated that tumor necrosis
      factor-alpha (TNF-alpha) treatment up-regulates miR-27 through the NF-kappaB
      pathway. Furthermore, anti-miR-27 reduces the TNF-alpha-induced inhibition of
      adipogenesis. Simultaneously, the levels of miR-27 expression were decreased in
      mature adipocytes of obese mice when compared with lean mice. Our data revealed a
      novel mechanism of miR-27 in the regulation of adipogenesis. 

PMID- 24903075
TI  - Toxic epidermal necrolysis and natural remedies.

PMID- 24903077
TI  - Psoriasis and risk of heart failure: a nationwide cohort study.
AB  - AIMS: Psoriasis is a common inflammatory disease that is associated with
      increased risk of cardiovascular disease, including myocardial infarction. Heart
      failure (HF) is independently associated with several cardiovascular risk factors
      and is a major cause of cardiovascular morbidity and mortality. The association
      between psoriasis and HF is unclear and we therefore investigated the risk of new
      onset HF in a nationwide cohort of psoriasis patients compared with the
      background population. METHODS: The study included the entire Danish population
      aged >=18 years followed from 1 January 1997 until HF, death or 31 December 2011.
      Information on comorbidity and concomitant medication was identified by
      individual-level linkage of administrative registers. New-onset HF was defined as
      first hospital admission for HF. Incidence rates of new-onset HF were calculated
      and adjusted hazard ratios were estimated by multivariable Cox regression models
      adjusted for age, gender, comorbidity and cardiovascular medications. RESULTS: A
      total of 5 485 856 subjects were eligible for analysis. In the study period 66
      389 patients with new-onset psoriasis, including 11 242 patients with severe
      psoriasis, were identified. The overall incidence rates of new-onset HF were
      2.82, 4.22 and 4.70 per 1000 person-years for the reference population, mild
      psoriasis and severe psoriasis, respectively. Compared with the reference
      population, the fully adjusted hazard ratios for new-onset HF were increased in
      patients with psoriasis with a hazard ratio 1.22 (95% confidence interval 1.16
      1.29) and hazard ratio of 1.53 (95% confidence interval 1.34-1.74) for those with
      mild and severe disease, respectively. CONCLUSION: In this nationwide cohort,
      psoriasis was associated with a disease severity-dependent increased risk of new
      onset HF.

PMID- 24903076
TI  - Reduced cerebral oxygen-carbohydrate index during endotracheal intubation in
      vascular surgical patients.
AB  - Brain activation reduces balance between cerebral consumption of oxygen versus
      carbohydrate as expressed by the so-called cerebral oxygen-carbohydrate-index
      (OCI). We evaluated whether preparation for surgery, anaesthesia including
      tracheal intubation and surgery affect OCI. In patients undergoing aortic
      surgery, arterial to internal jugular venous (a-v) concentration differences for
      oxygen versus lactate and glucose were determined from before anaesthesia to when
      the patient left the recovery room. Intravenous anaesthesia was supplemented with
      thoracic epidural anaesthesia for open aortic surgery (n = 5) and infiltration
      with bupivacaine for endovascular procedures (n = 14). The a-v difference for O2
      decreased throughout anaesthesia and in the recovery room (1.6 +/- 1.9 versus 3.2
      +/- 0.8 mmol l(-1), mean +/- SD), and while a-v glucose decreased during surgery
      and into the recovery (0.4 +/- 0.2 versus 0.7 +/- 0.2 mmol l(-1) , P<0.05), a-v
      lactate did not change significantly (0.03 +/- 0.16 versus -0.03 +/- 0.09 mmol l(
      1)). Thus, OCI decreased from 5.2 +/- 1.8 before induction of anaesthesia to 3.2
      +/- 1.0 following tracheal intubation (P<0.05) because of the decrease in a-v O2
      with a recovery for OCI to 4.6 +/- 1.4 during surgery and to 5.6 +/- 1.7 in the
      recovery room. In conclusion, preparation for surgery and tracheal intubation
      decrease OCI that recovers during surgery under the influence of sensory
      blockade.

PMID- 24903078
TI  - Group psychoeducative cognitive-behaviour therapy for mixed anxiety and
      depression with older adults.
AB  - OBJECTIVES: There is a dearth of older adult evidence regarding the group
      treatment for co-morbid anxiety and depression. This research evaluated the
      effectiveness of a low-intensity group psychoeducational approach. METHOD:
      Patients attended six sessions of a manualised cognitive-behavioural group.
      Validated measures of anxiety, depression and psychological well-being were taken
      at assessment, termination and six-week follow-up from patients, who also rated
      the alliance and their anxiety/depression at each group session. Staff rated
      patients regarding their functioning at assessment, termination and six-week
      follow-up. Outcomes were categorised according to whether patients had recovered,
      improved, deteriorated or been harmed. Effect sizes were compared to extant group
      interventions for anxiety and depression. RESULTS: Eight groups were completed
      with 34 patients, with a drop-out rate of 17%. Staff and patient rated outcome
      measures showed significant improvements (with small effect sizes) in assessment
      to termination and assessment to follow-up comparisons. Over one quarter (26.47%)
      of patients met the recovery criteria at follow-up and no patients were harmed.
      Outcomes for anxiety were better than for depression with the alliance in groups
      stable over time. CONCLUSION: The intervention evaluated shows clinical and
      organisational promise. The group approach needs to be further developed and
      tested in research with greater methodological control.

PMID- 24903079
TI  - Increased lung cancer risk in patients with interstitial lung disease and
      elevated CEA and CA125 serum tumour markers.
AB  - BACKGROUND AND OBJECTIVE: The aetiology and pathogenesis of interstitial lung
      disease (ILD) and ILD combined with lung cancer (ILD-CA) are unclear. We aim to
      investigate serum tumour marker (STM) levels and to explore their predictive and
      diagnostic value of cancer in ILD. METHODS: Fifty-eight patients with ILD-CA, 632
      with ILD only and 628 with acute respiratory illness were studied. Serum levels
      of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA125 and
      neuron-specific enolase (NSE) were measured. RESULTS: All STM levels were
      elevated in ILD-CA compared with ILD group (P < 0.01). CEA and CA125 levels were
      significantly higher in ILD than in controls (P < 0.01). After adjustment for
      gender, age and smoking, ILD-CA risk in the CEA and CA125 fourth quartiles was
      increased compared with the first quartiles (CEA: odds ratio (OR) = 8.7, 95%
      confidence interval (CI) = 2.0-37.6; CA125: OR = 9.8, 95% CI = 2.3-42.7).
      Receiver operating characteristic (ROC) curve analysis in patients with ILD-CA
      showed a cut-off points of 3.99 ng/mL for CEA and 35.00 U/mL for CA125 with
      sensitivities of 74.6% and 71.9%, specificities 70.4% and 66.1%, and the areas
      under the curve 0.76 (95% CI = 0.69-0.82) and 0.75 (95% CI = 0.69-0.81),
      respectively. CONCLUSIONS: Serum CEA and CA125 levels are often elevated in ILD
      patients. The risk of cancer in ILD is increased with an elevation of serum CEA
      and CA125 levels. Serum CEA and CA125 levels may be a marker of cancer in ILD
      patients.

PMID- 24903080
TI  - Validation and comparison of CS-IHC4 scores with a nomogram to predict recurrence
      in hormone receptor-positive breast cancers.
AB  - The aim of this study was to both develop and validate a nomogram based on the Ki
      67 index to predict recurrence. We constructed a nomogram using the Cox
      proportional hazards model with 953 N0 and N1 postoperative hormone receptor (HR)
      positive breast cancer patients and validated it in an external cohort of 895
      patients. A prognostic model that used classical variables, Adjuvant! Online, St.
      Gallen risk stratification, and the four immunohistochemistry (IHC) markers (IHC4
      score) was created and assessed by the likelihood ratio chi(2) (LR-chi(2)) test
      using the bootstrapping method. The nomogram showed an area under the receiver
      operating characteristic curve (AUC) of 0.75 (95% CI 0.72-0.77) in the training
      set. The validation set showed good discrimination with an AUC of 0.63 (95% CI
      0.60-0.66). In the LR-chi(2) test, the nomogram score was found to be more
      informative than the IHC4 with clinical score (CS) [LR-chi(2) 13.365 (1 d.f.);
      95% CI 2.50-24.23 for CS-IHC4 + nomogram score vs. CS-IHC4] on distant recurrence
      free survival. This study implies that the amount of prognostic information
      contained in the nomogram is superior to that in the CS-IHC4 score in HR-positive
      N0 and N1 breast cancer patients (NCT1273415).

PMID- 24903081
TI  - Structural and functional cardiac adaptations to 6 months of football training in
      untrained hypertensive men.
AB  - We investigated the effects of 3 and 6 months of regular football training on
      cardiac structure and function in hypertensive men. Thirty-one untrained males
      with mild-to-moderate hypertension were randomized 2:1 to a football training
      group (n = 20) and a control group receiving traditional recommendations on
      healthy lifestyle (n = 11). Cardiac measures were evaluated by echocardiography.
      The football group exhibited significant (P < 0.05) changes in cardiac dimensions
      and function after just 3 months: Left ventricular (LV) end-diastolic volume
      increased from 104 +/- 25 to 117 +/- 29 mL. LV diastolic function improved
      measured as E/A ratio (1.15 +/- 0.32 to 1.54 +/- 0.38), early diastolic velocity,
      E' (11.0 +/- 2.5 to 11.9 +/- 2.6 cm/s), and isovolumetric relaxation time (74 +/-
      13 to 62 +/- 13 ms). LV systolic function improved measured as longitudinal
      displacement (10.7 +/- 2.1 to 12.1 +/- 2.3 mm). Right ventricular function
      improved with respect to tricuspid annular plane systolic excursion (21.8 +/- 3.2
      to 24.5 +/- 3.7 mm). Arterial blood pressure decreased in both groups, but
      significantly more in the football training group. No significant changes were
      observed in the control group. In conclusion, short-term football training
      improves LV diastolic function in untrained men with mild-to-moderate arterial
      hypertension. Furthermore, it may improve longitudinal systolic function of both
      ventricles. The results suggest that football training has favorable effects on
      cardiac function in hypertensive men.

PMID- 24903082
TI  - Tyrosinase-catalyzed oxidation of rhododendrol produces 2-methylchromane-6,7
      dione, the putative ultimate toxic metabolite: implications for melanocyte
      toxicity.
AB  - RS-4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD) was used as a skin-whitening
      agent until it was reported to induce leukoderma in July 2013. To explore the
      mechanism underlying its melanocyte toxicity, we characterized the tyrosinase
      catalyzed oxidation of RD using spectrophotometry and HPLC. Oxidation of RD with
      mushroom tyrosinase rapidly produced RD-quinone, which was quickly converted to 2
      methylchromane-6,7-dione (RD-cyclic quinone) and RD-hydroxy-p-quinone through
      cyclization and addition of water molecule, respectively. RD-quinone and RD
      cyclic quinone were identified as RD-catechol and RD-cyclic catechol after NaBH4
      reduction. Autoxidation of RD-cyclic catechol produced superoxide radical. RD
      quinone and RD-cyclic quinone quantitatively bound to thiols such as cysteine and
      GSH. These results suggest that the melanocyte toxicity of RD is caused by its
      tyrosinase-catalyzed oxidation through production of RD-cyclic quinone which
      depletes cytosolic GSH and then binds to essential cellular proteins through
      their sulfhydryl groups. The production of ROS through autoxidation of RD-cyclic
      catechol may augment the toxicity. 

PMID- 24903083
TI  - Prognostic and diagnostic value of eosinopenia, C-reactive protein,
      procalcitonin, and circulating cell-free DNA in critically ill patients admitted
      with suspicion of sepsis.
AB  - INTRODUCTION: The aims of this study were to assess the reliability of
      circulating cell-free DNA (cf-DNA) concentrations, compared with C-reactive
      protein (CRP), procalcitonin (PCT) and eosinophil count, in the diagnosis of
      infections in patients with systemic inflammatory response syndrome (SIRS) and
      their prognostic values in a cohort of critically ill patients. METHODS: We
      conducted a prospective cohort study in a medical-surgical intensive care unit of
      a university hospital. Eosinophil count and concentrations of cf-DNA, CRP, and
      PCT were measured in patients who fulfilled SIRS criteria at admission to the
      intensive care unit (ICU) and a second determination 24 hours later. DNA levels
      were determined by a PCR method using primers for the human beta-haemoglobin
      gene. RESULTS: One hundred and sixty consecutive patients were included: 43 SIRS
      without sepsis and 117 with sepsis. Levels of CRP and PCT, but not cf-DNA or
      eosinophil count, were significantly higher in patients with sepsis than in SIRS
      no sepsis group on days 1 and 2. PCT on day 1 achieves the best area under the
      curve (AUC) for sepsis diagnosis (0.87; 95% confidence interval = 0.81-0.94).
      Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for
      mortality prediction was lower than that shown by APACHE II score. PCT decreases
      significantly from day 1 to day 2 in survivors in the entire cohort and in
      patients with sepsis without significant changes in the other biomarkers.
      CONCLUSIONS: Our data do not support the clinical utility of cf-DNA measurement
      in critical care patients with SIRS. PCT is of value especially for infection
      identification in patients with SIRS at admission to the ICU.

PMID- 24903085
TI  - Unravelling the annual cycle in a migratory animal: breeding-season habitat loss
      drives population declines of monarch butterflies.
AB  - Threats to migratory animals can occur at multiple periods of the annual cycle
      that are separated by thousands of kilometres and span international borders.
      Populations of the iconic monarch butterfly (Danaus plexippus) of eastern North
      America have declined over the last 21 years. Three hypotheses have been posed to
      explain the decline: habitat loss on the overwintering grounds in Mexico, habitat
      loss on the breeding grounds in the United States and Canada, and extreme weather
      events. Our objectives were to assess population viability, determine which life
      stage, season and geographical region are contributing the most to population
      dynamics and test the three hypotheses that explain the observed population
      decline. We developed a spatially structured, stochastic and density-dependent
      periodic projection matrix model that integrates patterns of migratory
      connectivity and demographic vital rates across the annual cycle. We used
      perturbation analysis to determine the sensitivity of population abundance to
      changes in vital rate among life stages, seasons and geographical regions. Next,
      we compared the singular effects of each threat to the full model where all
      factors operate concurrently. Finally, we generated predictions to assess the
      risk of host plant loss as a result of genetically modified crops on current and
      future monarch butterfly population size and extinction probability. Our year
      round population model predicted population declines of 14% and a quasi
      extinction probability (<1000 individuals) >5% within a century. Monarch
      abundance was more than four times more sensitive to perturbations of vital rates
      on the breeding grounds than on the wintering grounds. Simulations that
      considered only forest loss or climate change in Mexico predicted higher
      population sizes compared to milkweed declines on the breeding grounds. Our model
      predictions also suggest that mitigating the negative effects of genetically
      modified crops results in higher population size and lower extinction risk.
      Recent population declines stem from reduction in milkweed host plants in the
      United States that arise from increasing adoption of genetically modified crops
      and land-use change, not from climate change or degradation of forest habitats in
      Mexico. Therefore, reducing the negative effects of host plant loss on the
      breeding grounds is the top conservation priority to slow or halt future
      population declines of monarch butterflies in North America. 

PMID- 24903086
TI  - Early second-trimester molar tooth sign.
AB  - Molar tooth sign (MTS) is pathognomonic for Joubert syndrome (JS) and related
      disorders. We report a case in which MTS was suspected in an 'at risk' patient at
      16 weeks' gestation by sonography and at 18 weeks by additional ultrasound. It
      was then confirmed at 20 weeks by MRI. A molecular diagnosis of JS was
      established after termination of the pregnancy. As genetic testing may not be
      feasible in JS, the ability to identify MTS sonographically as early as possible
      is important for affected families.

PMID- 24903084
TI  - Bond strength of calcium silicate-based sealers to dentine dried with different
      techniques.
AB  - OBJECTIVE: To assess the influence of various canal-drying techniques on the push
      out bond strength between radicular dentine and both MTA Fillapex and iRoot SP
      sealers. MATERIALS AND METHODS: Eighty extracted single-root teeth were
      instrumented with ProTaper Universal rotary instruments to a size F4. The teeth
      were randomly assigned to 1 of 4 groups as follows: group 1, excess fluid in the
      canals was removed using a Luer vacuum adapter; group 2, the canals were dried
      with a single paper point; group 3, the canals were dried with 3-5 paper points,
      and group 4, the canals were rinsed with 95% ethanol and then dried with 3-5
      paper points. In each group, the specimens were subgrouped according to root
      canal sealer into either subgroup A (MTA Fillapex) or subgroup B (iRoot SP
      sealer). Horizontal sections (thickness 1 +/- 0.1 mm) were obtained from each
      specimen and a push-out test was performed using a universal testing machine at a
      crosshead speed of 1 mm/min on root slices. Statistical analysis was done using
      the Kruskal-Wallis test and Dunn's test for pair-wise comparisons. p < 0.05 was
      considered statistically significant. RESULTS: Canals dried with only 1 paper
      point and obturated with the iRoot SP sealer (subgroup 2B) showed significantly
      higher bond strengths to the root canal wall compared to all other subgroups (p <
      0.05), except for subgroup 1B (p > 0.05). CONCLUSIONS: The canal-drying technique
      influenced the adhesive bond strength between calcium silicate-based root canal
      sealers and the root canal wall.

PMID- 24903087
TI  - Explaining the unexplainable - the impact of physicians' attitude towards
      litigation on their incident disclosure behaviour.
AB  - RATIONALE, AIMS AND OBJECTIVES: This study aims to provide in-depth insight into
      the emotions and thoughts of physicians towards malpractice litigation, and how
      these relate to their incident disclosure behaviour. METHODS: Thirty-one Dutch
      physicians were interviewed and completed short questionnaires regarding
      malpractice litigation. We used hierarchical cluster analysis to identify
      physician clusters. Additional qualitative data were analysed. RESULTS:
      Physicians vary largely in their attitude towards malpractice litigation, and
      their attitude is not straightforward related to their disclosure behaviour.
      Based on their responses physicians could be divided into two clusters: one with
      a positive and one with a negative attitude. Physicians with a negative attitude
      showed often, but also 6 out of 15 not, a reluctance to disclose, whereas the
      majority in the positive attitude cluster (12 out of 16) showed no reluctance.
      If, what and how physicians disclose incidents depends on a complex interplay of
      their emotions and thoughts regarding litigation, and not only on their fear of
      litigation as many studies assume. CONCLUSIONS: Due to the variation among
      physicians in their litigation attitude and behaviour in terms of incident
      disclosure the oft-heard call for 'openness' about medical incidents will not be
      easy to achieve. A coaching system in which physicians can share and discuss
      their differing attitudes and disclosure principles, teaching medical students
      and junior physicians about disclosure, and explaining how to organize emotional
      and legal support for oneself in case of litigation could decrease stress
      feelings and support open disclosure behaviour.

PMID- 24903088
TI  - Coral calcifying fluid pH dictates response to ocean acidification.
AB  - Ocean acidification driven by rising levels of CO2 impairs calcification,
      threatening coral reef growth. Predicting how corals respond to CO2 requires a
      better understanding of how calcification is controlled. Here we show how spatial
      variations in the pH of the internal calcifying fluid (pHcf) in coral (Stylophora
      pistillata) colonies correlates with differential sensitivity of calcification to
      acidification. Coral apexes had the highest pHcf and experienced the smallest
      changes in pHcf in response to acidification. Lateral growth was associated with
      lower pHcf and greater changes with acidification. Calcification showed a pattern
      similar to pHcf, with lateral growth being more strongly affected by
      acidification than apical. Regulation of pHcf is therefore spatially variable
      within a coral and critical to determining the sensitivity of calcification to
      ocean acidification. 

PMID- 24903089
TI  - Type-I interferon response affects an inoculation dose-independent mortality in
      mice following Japanese encephalitis virus infection.
AB  - BACKGROUND: The laboratory mouse model is commonly employed to study the
      pathogenesis of encephalitic flaviviruses such as Japanese encephalitis virus
      (JEV). However, it is known that some strains of these viruses do not elicit a
      typical mortality dose response curve from this organism after peripheral
      infection and the reason for it has not yet been fully understood. It is
      suggested that induction of more vigorous Type-I IFN (IFN-I) response might
      control early virus dissemination following increasing infectious challenge doses
      of the virus. Thus, the objective of this study was to examine this suggested
      role of IFN-I in the mortality of mice infected with various doses of JEV.
      METHODS: Inbred 129 mice and their IFNAR KO (A129) mice were subcutaneously
      inoculated with 100, 102, 104 or 106 pfu of JaOArS982 strain of JEV. Mice were
      weighed daily and observed for clinical signs. Virus titers in the brains and
      spleens of JEV-infected mice were determined by plaque forming assays. The
      upregulated mRNA levels of genes related to IFN-I response of mice were examined
      by real-time PCR. RESULTS: The mortality rates of 129 mice infected with
      JaOArS982 did not significantly increase despite the increase in inoculation dose
      and no significant difference of viral loads was observed between their brains.
      However, there was clear elevation of the mRNA levels of interferon regulatory
      factor (IRF)3, IRF7, IRF9, MDA5 and RIG-I at 24 hours post-infection depending on
      the inoculation dose. In A129 mice, length of survival days and the viral loads
      of spleen and brain were observed to be inoculation dose-dependent. CONCLUSIONS:
      From these results, it is suggested that early IFN-I response elicited by high
      inoculation doses of JEV provides an anti-viral effect during the early phase of
      infection. Accordingly, virus replication is counteracted by IFN-I response at
      each increasing inoculation dose resulting in the interference of impending
      severe disease course or fatal outcome; hence, this might explain the inoculation
      dose-independent mortality in mice caused by Japanese encephalitis virus.

PMID- 24903090
TI  - Adding selenium to chemotherapy and radiation in haematological malignancies:
      clinical trials are justified.

PMID- 24903091
TI  - Phosphoinositide 3-kinases p110alpha and p110beta have differential roles in
      insulin-like growth factor-1-mediated Akt phosphorylation and platelet priming.
AB  - OBJECTIVE: Platelet hyperactivity is a contributing factor in the pathogenesis of
      cardiovascular disease and can be induced by elevated levels of circulating
      growth factors, such as insulin-like growth factor-1 (IGF-1). IGF-1 is a primer
      that cannot stimulate platelet activation by itself, but in combination with
      physiological stimuli can potentiate platelet functional responses via a
      phosphoinositide 3-kinase-dependent mechanism. In this study, we explored the
      role of the phosphoinositide 3-kinase p110alpha isoform in IGF-1-mediated
      enhancement of platelet function. APPROACH AND RESULTS: Using a platelet-specific
      p110alpha knockout murine model, we demonstrate that genetic deletion, similar to
      pharmacological inactivation of p110alpha, did not affect proteinase-activated
      receptor 4 signaling to Akt/protein kinase B but significantly reduced IGF-1
      mediated Akt phosphorylation. The p110beta inhibitor TGX-221 abolished IGF-1
      induced Akt phosphorylation in p110alpha-deficient platelets, demonstrating that
      both p110alpha and p110beta contribute to IGF-1-mediated Akt phosphorylation.
      Genetic deletion of p110alpha had no effect on IGF-1-mediated increases in
      thrombus formation on collagen and enhancement of proteinase-activated receptor 4
      mediated integrin activation and alpha-granule secretion. In contrast,
      pharmacological inhibition of p110alpha blocked IGF-1-mediated potentiation of
      integrin activation and alpha-granule secretion. Functional enhancement by IGF-1
      in p110alpha knockout samples was lost after TGX-221 treatment, suggesting that
      p110beta drives priming in the absence of the p110alpha isoform. CONCLUSIONS:
      Together, these results demonstrate that both p110alpha and p110beta are involved
      in Akt signaling by IGF-1, but that it is the p110alpha isoform that is
      responsible for IGF-1-mediated potentiation of platelet function.

PMID- 24903092
TI  - Antiangiogenic cancer drug using the zebrafish model.
AB  - The process of de novo vessel formation, called angiogenesis, is essential for
      tumor progression and spreading. Targeting of molecular pathways involved in such
      tumor angiogenetic processes by using specific drugs or inhibitors is important
      for developing new anticancer therapies. Drug discovery remains to be the main
      focus for biomedical research and represents the essence of antiangiogenesis
      cancer research. To pursue these molecular and pharmacological goals, researchers
      need to use animal models that facilitate the elucidation of tumor angiogenesis
      mechanisms and the testing of antiangiogenic therapies. The past few years have
      seen the zebrafish system emerge as a valid model organism to study developmental
      angiogenesis and, more recently, as an alternative vertebrate model for cancer
      research. In this review, we will discuss why the zebrafish model system has the
      advantage of being a vertebrate model equipped with easy and powerful
      transgenesis as well as imaging tools to investigate not only physiological
      angiogenesis but also tumor angiogenesis. We will also highlight the potential of
      zebrafish for identifying antitumor angiogenesis drugs to block tumor development
      and progression. We foresee the zebrafish model as an important system that can
      possibly complement well-established mouse models in cancer research to generate
      novel insights into the molecular mechanism of the tumor angiogenesis. 

PMID- 24903093
TI  - Oxidized low-density lipoprotein induces long-term proinflammatory cytokine
      production and foam cell formation via epigenetic reprogramming of monocytes.
AB  - OBJECTIVE: Although the role of monocytes in the pathogenesis of atherosclerosis
      is well established, the persistent vascular inflammation remains largely
      unexplained. Recently, our group reported that stimulation of monocytes with
      various microbial products can induce a long-lasting proinflammatory phenotype
      via epigenetic reprogramming, a process termed trained immunity. We now
      hypothesize that oxidized low-density lipoprotein (oxLDL) also induces a long
      lasting proinflammatory phenotype in monocytes, which accelerates atherosclerosis
      by proinflammatory cytokine production and foam cell formation. APPROACH AND
      RESULTS: Isolated human monocytes were exposed for 24 hours to medium or oxLDL.
      After washing and resting for 6 days, the cells were exposed to toll-like
      receptor 2 and 4 agonists. Pre-exposure to oxLDL increased mRNA expression and
      protein formation on toll-like receptor 2 and 4 stimulation of several
      proatherogenic proteins, including interleukin-6, interleukin-18, interleukin-8,
      tumor necrosis factor-alpha, monocyte chemoattractant protein 1, and matrix
      metalloproteinase 2 and 9. In addition, foam cell formation was enhanced after
      oxLDL exposure, which was associated with an upregulation of scavenger receptors
      CD36 and scavenger receptor-A and downregulation of ATP-binding cassette
      transporters, ABCA1 and ABCG1. Chromatin immunoprecipitation performed 6 days
      after oxLDL stimulation demonstrated increased trimethylation of lysine 4 at
      histone 3 in promoter regions of tnfalpha, il-6, il-18, mcp-1, mmp2, mmp9, cd36,
      and sr-a. Finally, pretreatment of the monocytes with the histone
      methyltransferase inhibitor methylthioadenosine completely prevented the oxLDL
      induced long-lasting proinflammatory phenotype. CONCLUSIONS: Brief exposure of
      monocytes to a low concentration of oxLDL induces a long-lasting proatherogenic
      macrophage phenotype via epigenetic histone modifications, characterized by
      increased proinflammatory cytokine production and foam cell formation.

PMID- 24903094
TI  - Alternative splicing of endothelial fibronectin is induced by disturbed
      hemodynamics and protects against hemorrhage of the vessel wall.
AB  - OBJECTIVE: Abnormally low-flow conditions, sensed by the arterial endothelium,
      promote aneurysm rupture. Fibronectin (FN) is among the most abundant
      extracellular matrix proteins and is strongly upregulated in human aneurysms,
      suggesting a possible role in disease progression. Altered FN splicing can result
      in the inclusion of EIIIA and EIIIB exons, generally not expressed in adult
      tissues. We sought to explore the regulation of FN and its splicing and their
      possible roles in the vascular response to disturbed flow. APPROACH AND RESULTS:
      We induced low and reversing flow in mice by partial carotid ligation and assayed
      FN splicing in an endothelium-enriched intimal preparation. Inclusion of EIIIA
      and EIIIB was increased as early as 48 hours, with negligible increases in total
      FN expression. To test the function of EIIIA and EIIIB inclusion, we induced
      disturbed flow in EIIIAB(-/-) mice unable to include these exons and found that
      they developed focal lesions with hemorrhage and hypertrophy of the vessel wall.
      Acute deletion of floxed FN caused similar defects in response to disturbed flow,
      consistent with a requirement for the upregulation of the spliced isoforms,
      rather than a developmental defect. Recruited macrophages promote FN splicing
      because their depletion by clodronate liposomes blocked the increase in
      endothelial EIIIA and EIIIB inclusion in the carotid model. CONCLUSIONS: These
      results uncover a protective mechanism in the inflamed intima that develops under
      disturbed flow, by showing that splicing of FN mRNA in the endothelium, induced
      by macrophages, inhibits hemorrhage of the vessel wall.

PMID- 24903095
TI  - Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography
      for noninvasive characterization of vulnerable plaques: correlation with in vivo
      17.6T MRI.
AB  - OBJECTIVE: Nuclear imaging of active plaques still remains challenging. Advanced
      atherosclerotic plaques have a strong expression of P-selectin by the endothelium
      overlying active atherosclerotic plaques, but not on the endothelium overlying
      inactive fibrous plaques. We proposed a new approach for noninvasive in vivo
      characterization of P-selectin on active plaques based on (68)Ga-Fucoidan, which
      is a polysaccharidic ligand of P-selectin with a nanomolar affinity. APPROACH AND
      RESULTS: (68)Ga-Fucoidan was tested for its potential to discriminate vulnerable
      plaques on apolipoprotein E-deficient mice receiving a high cholesterol diet by
      positron emission tomography and in correlation with 17.6T MRI. Furthermore,
      (68)Ga-Fucoidan was evaluated on endothelial cells in vitro and ex vivo on active
      plaques using autoradiography. The cellular uptake rate was increased ~2-fold by
      lipopolysaccharide induction. Interestingly, on autoradiography, more intensive
      tracer accumulation at active plaques with thin fibrous caps and high-density
      foam cells were observed in comparison with a weaker focal uptake in inactive
      fibrous plaque segments (R=1.7+/-0.3; P<0.05) and fatty streaks (R=2.4+/-0.4;
      P<0.01). Strong uptake of radiotracer colocalized with increased P-selectin
      expression and high-density macrophage. Focal vascular uptake (mean of target to
      background ratio=5.1+/-0.8) of (68)Ga-Fucoidan was detected in all apolipoprotein
      E-deficient mice. Anatomic structures of plaque were confirmed by 17.6T MRI. The
      autoradiography showed a good agreement of (68)Ga-Fucoidan uptake with positron
      emission tomography. CONCLUSIONS: Our data suggest that (68)Ga-Fucoidan
      represents a versatile imaging biomarker for P-selectin with the potential to
      specifically detect P-selectin expression using positron emission tomography and
      to discriminate vulnerable plaques in vivo.

PMID- 24903096
TI  - Association between shear stress and platelet-derived transforming growth factor
      beta1 release and activation in animal models of aortic valve stenosis.
AB  - OBJECTIVE: Aortic valve stenosis (AS) is characterized by fibrosis and
      calcification of valves leading to aortic valve narrowing, resulting in high wall
      shear stress across the valves. We previously demonstrated that high shear stress
      can activate platelet-derived transforming growth factor-beta1 (TGF-beta1), a
      cytokine that induces fibrosis and calcification. The aim of this study was to
      investigate the role of shear-induced platelet release of TGF-beta1 and its
      activation in AS. APPROACH AND RESULTS: We studied hypercholesterolemic Ldlr(-/
      )Apob(100/100)/Mttp(fl/fl)/Mx1Cre(+/+) (Reversa) mice that develop AS on Western
      diet and a surgical ascending aortic constriction mouse model that acutely
      simulates the hemodynamics of AS to study shear-induced platelet TGF-beta1
      release and activation. Reversa mice on Western diet for 6 months had thickening
      of the aortic valves, increased wall shear stress, and increased plasma TGF-beta1
      levels. There were weak and moderate correlations between wall shear stress and
      TGF-beta1 levels in the progression and reversed Reversa groups and a stronger
      correlation in the ascending aortic constriction model in wild-type mice but not
      in mice with a targeted deletion of megakaryocyte and platelet TGF-beta1
      (Tgfb1(flox)). Plasma total TGF-beta1 levels correlated with collagen deposition
      in the stenotic valves in Reversa mice. Although active TGF-beta1 levels were too
      low to be measured directly, we found (1) canonical TGF-beta1 (phosphorylated
      small mothers against decapentaplegic 2/3) signaling in the leukocytes and
      canonical and noncanonical (phosphorylated extracellular signal-regulated kinases
      1/2) TGF-beta1 signaling in aortic valves of Reversa mice on a Western diet, and
      (2) TGF-beta1 signaling of both pathways in the ascending aortic constriction
      stenotic area in wild-type but not Tgfb1(flox) mice. CONCLUSIONS: Shear-induced,
      platelet-derived TGF-beta1 activation may contribute to AS.

PMID- 24903098
TI  - Immunoglobulin G values before treatment are correlated with the responsiveness
      to initial intravenous immunoglobulin therapy for Kawasaki disease.
AB  - BACKGROUND: Low levels of serum immunoglobulin G (IgG) before intravenous
      immunoglobulin (IVIG) therapy for Kawasaki disease (KD) have been reported as one
      of the risk factors for coronary artery abnormalities (CAAs). This risk factor
      needs to be re-evaluated because the dosage of IVIG has changed from 0.2-0.4
      g/kg/day for 5 days to a single high dose of 2 g/kg. METHODS: We reviewed the
      clinical records of KD patients admitted to our hospital from January 2001 to
      August 2011. Patients who were given a single high dose of IVIG within 7 days of
      illness, and who had blood collected for serum immunoglobulin values before
      treatment, were selected. The serum immunoglobulin levels and coronary artery
      diameters measured by echocardiogram were transformed to z-scores. RESULTS: The
      subjects were 197 KD patients, including 22 IVIG nonresponders and 16 patients
      with CAAs. Of these, 150 (76%) had a z-score for IgG (IgGz) of <=0. There were no
      differences in IgGz values between patients with CAAs and those without CAAs.
      However, nonresponders had higher IgGz values than responders (median, 25th
      percentile and 75th percentile: -0.26, -0.83 and 0.34 vs. -0.79, -1.40 and -0.03;
      p = 0.020). Logistic regression analysis showed that the IgGz value was an
      independent risk factor for resistance to IVIG (OR 1.36, 95% CI 1.002-1.849; p =
      0.048). CONCLUSIONS: Low IgGz values were not a risk factor for CAAs in this
      study. However, KD patients with relatively high IgGz values before treatment may
      have an increased risk of resistance to initial IVIG therapy. (c) 2014 S. Karger
      AG, Basel.

PMID- 24903097
TI  - Interacting mechanisms in the pathogenesis of cardiac allograft vasculopathy.
AB  - Cardiac allograft vasculopathy is the major cause of late graft loss in heart
      transplant recipients. Histological studies of characteristic end-stage lesions
      reveal arterial changes consisting of a diffuse, confluent, and concentric
      intimal expansion containing graft-derived cells expressing smooth muscle
      markers, extracellular matrix, penetrating microvessels, and a host mononuclear
      cell infiltrate concentrated subjacent to an intact graft-derived luminal
      endothelial cell lining with little evidence of acute injury. This intimal
      expansion combined with inadequate compensatory outward remodeling produces
      severe generalized stenosis extending throughout the epicardial and
      intramyocardial arterial tree that causes ischemic graft failure. Cardiac
      allograft vasculopathy lesions affect >=50% of transplant recipients and are both
      progressive and refractory to treatment, resulting in ~5% graft loss per year
      through the first 10 years after transplant. Lesions typically stop at the suture
      line, implicating alloimmunity as the primary driver, but pathogenesis may be
      multifactorial. Here, we will discuss 6 potential contributors to lesion
      formation (1) conventional risk factors of atherosclerosis; (2) pre- or
      peritransplant injuries; (3) infection; (4) innate immunity; (5) T-cell-mediated
      immunity; and (6) B-cell-mediated immunity through production of donor-specific
      antibody. Finally, we will consider how these various mechanisms may interact
      with each other. 

PMID- 24903100
TI  - A charge optimized many-body potential for titanium nitride (TiN).
AB  - This work presents a new empirical, variable charge potential for TiN systems in
      the charge-optimized many-body potential framework. The potential parameters were
      determined by fitting them to experimental data for the enthalpy of formation,
      lattice parameters, and elastic constants of rocksalt structured TiN. The
      potential does a good job of describing the fundamental physical properties
      (defect formation and surface energies) of TiN relative to the predictions of
      first-principles calculations. This potential is used in classical molecular
      dynamics simulations to examine the interface of fcc-Ti(0 0 1)/TiN(0 0 1) and to
      characterize the adsorption of oxygen atoms and molecules on the TiN(0 0 1)
      surface. The results indicate that the potential is well suited to model TiN thin
      films and to explore the chemistry associated with their oxidation.

PMID- 24903099
TI  - Higher working memory predicts slower functional decline in autopsy-confirmed
      Alzheimer's disease.
AB  - BACKGROUND: There is heterogeneity in the pattern of early cognitive deficits in
      Alzheimer's disease (AD). However, whether the severity of initial cognitive
      deficits relates to different clinical trajectories of AD progression is unclear.
      OBJECTIVE: To determine if deficits in specific cognitive domains at the initial
      visit relate to the rate of progression in clinical trajectories of AD dementia.
      METHODS: 68 subjects from the National Alzheimer's Coordinating Center database
      who had autopsy-confirmed AD as the primary diagnosis and at least 3 serial
      assessments a year apart, with a Mini-Mental State Examination (MMSE) score >15
      and a Clinical Dementia Rating Scale-Global (CDR-G) score <=1 at the initial
      visit were included. A mixed regression model was used to examine the association
      between initial neuropsychological performance and rate of change on the MMSE and
      CDR Sum of Boxes. RESULTS: Preservation of working memory, but not episodic
      memory, in the mild cognitive impairment and early dementia stages of AD relates
      to slower rate of functional decline. DISCUSSION: These findings are relevant for
      estimating the rate of decline in AD clinical trials and in counseling patients
      and families. Improving working memory performance as a possible avenue to
      decrease the rate of functional decline in AD dementia warrants closer
      investigation.

PMID- 24903101
TI  - Manganese-mefenamic acid complexes exhibit high lipoxygenase inhibitory activity.
AB  - The coordination of non-steroidal anti-inflammatory drugs (NSAIDs) to metal ions
      could improve the pharmaceutical efficacy of NSAIDs due to the unique
      characteristics of metal complexes. However, the structures of many metal-NSAID
      complexes are not well characterized; the functional mechanism and pharmaceutical
      effect of these complexes thus are not fully understood. In this work, three
      manganese-mefenamic acid (Mn-mef) complexes were synthesized and structurally
      characterized, and their pharmaceutical effect was investigated. We found that
      the three Mn-mef complexes exhibit higher lipoxygenase (LOX-1) inhibitory
      activity (IC50 values are 16.79, 38.63 and 28.06 MUM, respectively) than the
      parent ligand mefenamic acid (78.67 MUM). More importantly, the high inhibitory
      activity of the Mn-mef complexes is closely related to their spatial
      arrangements, which determine their interaction with LOX-1. Computer docking of
      the Mn-mef complexes with the LOX-1 confirms the experimental results: smaller Mn
      mef complexes tend to bind competitively to LOX-1 at the substrate binding site,
      which is also analogous to the binding of the ligand mefenamic acid, while the
      bulky metal complexes inhibit the enzyme activity un-competitively. In addition,
      the Mn-mef complexes exhibit higher anti-oxidant activity than the ligand
      mefenamic acid. The higher anti-oxidant activity of the Mn-mef complexes
      apparently originated from the manganese centre of the complexes. We thus
      conclude that Mn-mef complexes enhance the anti-inflammatory activity of
      mefenamic acid by increasing their activity via changing their interaction mode
      with the enzymes, and/or by improving their anti-oxidant ability using metal
      ions. This work provides experimental evidence that with the unique spatial
      arrangements, metal-NSAID complexes could interact with the target enzymes more
      specifically and efficiently, which is superior to their parent NSAID ligand. 

PMID- 24903102
TI  - Cerium(III)-catalyzed cascade cyclization: an efficient approach to
      functionalized pyrrolo[1,2-a]quinolines.
AB  - A general and practical route to the synthesis of multisubstituted pyrrolo[1,2
      a]quinolines has been described from 2-alkylazaarenes and nitroolefins using
      cerium chloride as a catalyst via a tandem Michael addition, cyclization and
      aromatization. This protocol features readily available starting materials,
      operational simplicity and high regioselectivity to access multifunctionalized
      pyrrolo[1,2-a]quinolines with the formation of multiple C-C and C-N bonds in one
      pot. In addition, various substitution patterns and functional groups were found
      to be compatible under the optimized conditions, which was lacking in the
      existing procedures. 

PMID- 24903103
TI  - OxLDL triggers retrograde translocation of arginase2 in aortic endothelial cells
      via ROCK and mitochondrial processing peptidase.
AB  - RATIONALE: Increased arginase activity contributes to endothelial dysfunction by
      competition for l-arginine substrate and reciprocal regulation of nitric oxide
      synthase (NOS). The rapid increase in arginase activity in human aortic
      endothelial cells exposed to oxidized low-density lipoprotein (OxLDL) is
      consistent with post-translational modification or subcellular trafficking.
      OBJECTIVE: To test the hypotheses that OxLDL triggers reverse translocation of
      mitochondrial arginase 2 (Arg2) to cytosol and Arg2 activation, and that this
      process is dependent on mitochondrial processing peptidase, lectin-like OxLDL
      receptor-1 receptor, and rho kinase. METHODS AND RESULTS: OxLDL-triggered
      translocation of Arg2 from mitochondria to cytosol in human aortic endothelial
      cells and in murine aortic intima with a concomitant rise in arginase activity.
      All of these changes were abolished by inhibition of mitochondrial processing
      peptidase or by its siRNA-mediated knockdown. Rho kinase inhibition and the
      absence of the lectin-like OxLDL receptor-1 in knockout mice also ablated
      translocation. Aminoterminal sequencing of Arg2 revealed 2 candidate
      mitochondrial targeting sequences, and deletion of either of these confined Arg2
      to the cytoplasm. Inhibitors of mitochondrial processing peptidase or lectin-like
      OxLDL receptor-1 knockout attenuated OxLDL-mediated decrements in endothelial
      specific NO production and increases in superoxide generation. Finally, Arg2(-/-)
      mice bred on an ApoE(-/-) background showed reduced plaque load, reduced reactive
      oxygen species production, enhanced NO, and improved endothelial function when
      compared with ApoE(-/-) controls. CONCLUSIONS: These data demonstrate dual
      distribution of Arg2, a protein with an unambiguous mitochondrial targeting
      sequence, in mammalian cells, and its reverse translocation to cytoplasm by
      alterations in the extracellular milieu. This novel molecular mechanism drives
      OxLDL-mediated arginase activation, endothelial NOS uncoupling, endothelial
      dysfunction, and atherogenesis.

PMID- 24903105
TI  - The gender gap in sickness absence: long-term trends in eight European countries.
AB  - BACKGROUND: Most studies show that women have considerably higher rates of
      sickness absence than men, but little is known on how the gender gap has
      developed over time. METHODS: Data are taken from the EU Labour Force Surveys.
      The dependent variable is whether the respondent reports being away from work the
      entire reference week or not. Trends are shown from 1980 onwards. Poisson
      regression is used to estimate relative risks for women vs. men, with various
      sets of control variables. RESULTS: Increasing gross differences in sickness
      absence between women and men are found in five countries: Spain, Ireland,
      France, Belgium and the UK. No trend in the gender gap is found in Netherlands
      and Portugal, and probably even in Italy. The trends in the gender gap have been
      largely the same for men and women without children at home as in the population
      as a whole. The trends are little affected by control for detailed occupation and
      industry. CONCLUSION: The gender gap in sickness absence has increased in five
      out of eight countries. This is not due to increased labour force participation
      by mothers of small children, and neither can it be explained as a result of
      changes in how women and men are distributed across occupations or industries.

PMID- 24903104
TI  - AT2 receptor activation induces natriuresis and lowers blood pressure.
AB  - RATIONALE: Compound 21 (C-21) is a highly selective nonpeptide AT2 receptor
      (AT2R) agonist. OBJECTIVE: To test the hypothesis that renal proximal tubule
      AT2Rs induce natriuresis and lower blood pressure in Sprague-Dawley rats and
      mice. METHODS AND RESULTS: In rats, AT2R activation with intravenous C-21
      increased urinary sodium excretion by 10-fold (P<0.0001); this natriuresis was
      abolished by direct renal interstitial infusion of specific AT2R antagonist PD
      123319. C-21 increased fractional excretion of Na(+) (P<0.05) and lithium
      (P<0.01) without altering renal hemodynamic function. AT2R activation increased
      renal proximal tubule cell apical membrane AT2R protein (P<0.001) without
      changing total AT2R expression and internalized/inactivated Na(+)-H(+) exchanger
      3 and Na(+)/K(+)ATPase. C-21-induced natriuresis was accompanied by an increase
      in renal interstitial cGMP (P<0.01); C-21-induced increases in urinary sodium
      excretion and renal interstitial cGMP were abolished by renal interstitial nitric
      oxide synthase inhibitor l-N(6)-nitroarginine methyl ester or bradykinin B2
      receptor antagonist icatibant. Renal AT2R activation with C-21 prevented Na(+)
      retention and lowered blood pressure in the angiotensin II infusion model of
      experimental hypertension. CONCLUSIONS: AT2R activation initiates its
      translocation to the renal proximal tubule cell apical membrane and the
      internalization of Na(+)-H(+) exchanger-3 and Na(+)/K(+)ATPase, inducing
      natriuresis in a bradykinin-nitric oxide-cGMP-dependent manner. Intrarenal AT2R
      activation prevents Na(+) retention and lowers blood pressure in angiotensin II
      dependent hypertension. AT2R activation holds promise as a renal proximal tubule
      natriuretic/diuretic target for the treatment of fluid-retaining states and
      hypertension.

PMID- 24903106
TI  - Identifying and characterizing resting state networks in temporally dynamic
      functional connectomes.
AB  - An important application of resting state fMRI data has been to identify resting
      state networks (RSN). The conventional RSN studies attempted to discover
      consistent networks through functional connectivity analysis over the whole scan
      time, which implicitly assumes that RSNs are static. However, the brain undergoes
      dynamic functional state changes and the functional connectome patterns vary
      along with time, even in resting state. Hence, this study aims to characterize
      temporal brain dynamics in resting state. It utilizes the temporally dynamic
      functional connectome patterns to extract a set of resting state clusters and
      their corresponding RSNs based on the large-scale consistent, reproducible and
      predictable whole-brain reference system of dense individualized and common
      connectivity-based cortical landmarks (DICCCOL). Especially, an effective multi
      view spectral clustering method was performed by treating each dynamic functional
      connectome pattern as one view, and this procedure was also applied on static
      multi-subject functional connectomes to obtain the static clusters for
      comparison. It turns out that some dynamic clusters exhibit high similarity with
      static clusters, suggesting the stability of those RSNs including the visual
      network and the default mode network. Moreover, two motor-related dynamic
      clusters show correspondence with one static cluster, which implies substantially
      more temporal variability of the motor resting network. Particularly, four
      dynamic clusters exhibited large differences in comparison with their
      corresponding static networks. Thus it is suggested that these four networks
      might play critically important roles in functional brain dynamics and
      interactions during resting state, offering novel insights into the brain
      function and its dynamics. 

PMID- 24903107
TI  - Developments toward a low-cost approach for long-term, unattended vapor intrusion
      monitoring.
AB  - There are over 450 000 sites contaminated by chemicals in the US. This large
      number of contaminated sites and the speed of subsurface migration of chemicals
      pose considerable risk to nearby residences and commercial buildings. The high
      costs for monitoring around these sites stem from the labor involved in placing
      and replacing the passive sorbent vapor samplers and the resultant laboratory
      analysis. This monitoring produces sparse data sets that do not track temporal
      changes well. To substantially reduce costs and better track exposures, less
      costly, unattended systems for monitoring soil gases and vapor intrusion into
      homes and businesses are desirable to aid in the remediation of contaminated
      sites. This paper describes progress toward the development of an inexpensive
      system specifically for monitoring vapor intrusion; the system can operate
      repeatedly without user intervention with low detection limits (1 * 10(-9), or 1
      part-per-billion). Targeted analytes include chlorinated hydrocarbons
      (dichloroethylene, trichloroethane, trichloroethylene, and perchloroethylene) and
      benzene. The system consists of a trap-and-purge preconcentrator for vapor
      collection in conjunction with a compact gas chromatography instrument to
      separate individual compounds. Chemical detection is accomplished with an array
      of chemicapacitors and a metal-oxide semiconductor combustibles sensor. Both the
      preconcentrator and the chromatography column are resistively heated. All
      components are compatible with ambient air, which serves as the carrier gas for
      the gas chromatography and detectors. 

PMID- 24903108
TI  - Ribosome profiling reveals sequence-independent post-initiation pausing as a
      signature of translation.
AB  - The journey of a newly synthesized polypeptide starts in the peptidyltransferase
      center of the ribosome, from where it traverses the exit tunnel. The interior of
      the ribosome exit tunnel is neither straight nor smooth. How the ribosome
      dynamics in vivo is influenced by the exit tunnel is poorly understood. Genome
      wide ribosome profiling in mammalian cells reveals elevated ribosome density at
      the start codon and surprisingly the downstream 5th codon position as well. We
      found that the highly focused ribosomal pausing shortly after initiation is
      attributed to the geometry of the exit tunnel, as deletion of the loop region
      from ribosome protein L4 diminishes translational pausing at the 5th codon
      position. Unexpectedly, the ribosome variant undergoes translational abandonment
      shortly after initiation, suggesting that there exists an obligatory step between
      initiation and elongation commitment. We propose that the post-initiation pausing
      of ribosomes represents an inherent signature of the translation machinery to
      ensure productive translation. 

PMID- 24903110
TI  - Effect of therapeutic aquatic exercise on symptoms and function associated with
      lower limb osteoarthritis: systematic review with meta-analysis.
AB  - BACKGROUND: Current management of osteoarthritis (OA) focuses on pain control and
      maintaining physical function through pharmacological, nonpharmacological, and
      surgical treatments. Exercise, including therapeutic aquatic exercise (TAE), is
      considered one of the most important management options. Nevertheless, there is
      no up-to-date systematic review describing the effect of TAE on symptoms and
      function associated with lower limb OA. PURPOSE: The purpose of this study was to
      conduct a systematic review with meta-analysis to determine the effect of TAE on
      symptoms and function associated with lower limb OA. DATA SOURCES: The data
      sources used in this study were: MEDLINE, PubMed, EMBASE, CINAHL, PEDro, and
      SPORTDiscus. STUDY SELECTION: All studies selected for review were randomized
      controlled trials with an aquatic exercise group and a nontreatment control
      group. In total, 11 studies fulfilled the inclusion criteria and were included in
      the synthesis and meta-analysis. DATA EXTRACTION: Data were extracted and checked
      for accuracy by 3 independent reviewers. DATA SYNTHESIS: Standardized mean
      difference (SMD) with 95% confidence interval (95% CI) was calculated for all
      outcomes. The meta-analysis showed a significant TAE effect on pain (SMD=0.26
      [95% CI=0.11, 0.41]), self-reported function (SMD=0.30 [95% CI=0.18, 0.43]), and
      physical functioning (SMD=0.22 [95% CI=0.07, 0.38]). Additionally, a significant
      effect was seen on stiffness (SMD=0.20 [95% CI=0.03, 0.36]) and quality of life
      (SMD=0.24 [95% CI=0.04, 0.45]). LIMITATIONS: Heterogeneity of outcome measures
      and small sample sizes for many of the included trials imply that conclusions
      based on these results should be made with caution. CONCLUSIONS: The results
      indicate that TAE is effective in managing symptoms associated with lower limb
      OA.

PMID- 24903111
TI  - Professionalism in a digital age: opportunities and considerations for using
      social media in health care.
AB  - Since the beginning of the millennium, there has been a remarkable change in how
      people access and share information. Much of this information is user-generated
      content found on social media sites. As digital technologies and social media
      continue to expand, health care providers must adapt their professional
      communication to meet the expectations and needs of consumers. This adaptation
      may include communication on social media sites. However, many health care
      providers express concerns that professional social media use, particularly
      interactions with patients, is ethically problematic. Social media engagement
      does not create ethical dissonance if best practices are observed and online
      communication adheres to terms of service, professional standards, and
      organizational policy. A well-executed social media presence provides health care
      providers, including physical therapists, the opportunity-and perhaps a
      professional obligation-to use social media sites to share or create credible
      health care information, filling a consumer void for high-quality online
      information on fitness, wellness, and rehabilitation. This perspective article
      provides a broad review of the emergence of social media in society and health
      care, explores policy implications of organizational adoption of health care
      social media, and proposes individual opportunities and guidelines for social
      media use by the physical therapy professional. 

PMID- 24903112
TI  - Effectiveness of the canalith repositioning procedure in the treatment of benign
      paroxysmal positional vertigo.

PMID- 24903109
TI  - Receptor-mediated mitophagy in yeast and mammalian systems.
AB  - Mitophagy, or mitochondria autophagy, plays a critical role in selective removal
      of damaged or unwanted mitochondria. Several protein receptors, including Atg32
      in yeast, NIX/BNIP3L, BNIP3 and FUNDC1 in mammalian systems, directly act in
      mitophagy. Atg32 interacts with Atg8 and Atg11 on the surface of mitochondria,
      promoting core Atg protein assembly for mitophagy. NIX/BNIP3L, BNIP3 and FUNDC1
      also have a classic motif to directly bind LC3 (Atg8 homolog in mammals) for
      activation of mitophagy. Recent studies have shown that receptor-mediated
      mitophagy is regulated by reversible protein phosphorylation. Casein kinase 2
      (CK2) phosphorylates Atg32 and activates mitophagy in yeast. In contrast, in
      mammalian cells Src kinase and CK2 phosphorylate FUNDC1 to prevent mitophagy.
      Notably, in response to hypoxia and FCCP treatment, the mitochondrial phosphatase
      PGAM5 dephosphorylates FUNDC1 to activate mitophagy. Here, we mainly focus on
      recent advances in our understanding of the molecular mechanisms underlying the
      activation of receptor-mediated mitophagy and the implications of this catabolic
      process in health and disease. 

PMID- 24903113
TI  - Can physical therapists deliver a pain coping skills program? An examination of
      training processes and outcomes.
AB  - BACKGROUND: Physical therapists are well established as providers of treatments
      for common, painful, and disabling conditions, such as knee osteoarthritis (OA).
      Thus, they are well placed to deliver treatments that integrate physical and
      psychosocial elements. Attention is usually given to outcomes of such programs,
      but few studies have examined the processes and outcomes of training physical
      therapists to deliver such treatments. OBJECTIVE: The aim of this study was to
      describe the processes in training physical therapists: (1) to deliver a
      standardized pain coping skills treatment and (2) to evaluate the effectiveness
      of that training. DESIGN: This study was an analysis of data relating to
      therapist performance in a randomized clinical trial. METHODS: Eleven physical
      therapists were trained to deliver a 10-session pain coping skills training
      program for people with knee OA as part of a randomized controlled trial (N=222).
      The initial training was provided in a workshop format and included extensive,
      ongoing supervision by a psychologist and rigorous use of well-defined
      performance criteria to assess competence. Adherence to the program, ratings of
      performance, and use of advanced skills were all measured against these criteria
      in a sample (n=74, 10%) of the audio recordings of the intervention sessions.
      RESULTS: Overall, the physical therapists achieved a very high standard of
      treatment delivery, with 96.6% adherence to the program and mean performance
      ratings all in the satisfactory range. These results were maintained throughout
      the intervention and across all sessions. LIMITATIONS: Only 10% of the delivered
      sessions were analyzed, and the physical therapists who took part in the study
      were a self-selected group. CONCLUSIONS: This study demonstrated that a
      systematic approach to training and accrediting physical therapists to deliver a
      standardized pain coping skills program can result in high and sustained levels
      of adherence to the program. Training fidelity was achieved in this group of
      motivated clinicians, but the supervision provided was time intensive. The data
      provide a promising indicator of greater potential for psychologically informed
      practice to be a feature of effective health care.

PMID- 24903115
TI  - Stepping asymmetry among individuals with unilateral transtibial limb loss might
      be functional in terms of gait stability.
AB  - BACKGROUND: The asymmetry in step length in prosthetic gait is often seen as a
      detrimental effect of the impairment; however, this asymmetry also might be a
      functional compensation. An advantage of a smaller step length of the
      nonprosthetic leg, and specifically foot forward placement (FFP), might be that
      it will bring the center of mass closer to the base of support of the leading
      foot and thus increase the backward margin of stability (BW MoS). OBJECTIVE: The
      purpose of this study was to characterize differences in step length, FFP, and
      the concomitant difference in BW MoS between steps of the prosthetic and
      nonprosthetic legs (referred to as prosthetic and nonprosthetic steps,
      respectively) of people after transtibial amputation. DESIGN: This was an
      observational and cross-sectional study. METHODS: Ten people after transtibial
      amputation walked for 4 minutes on a self-paced treadmill. Step length and FFP
      were calculated at initial contact. The size of the BW MoS was calculated for the
      moment of initial contact and at the end of the double-support phase of gait.
      RESULTS: Step length (5.4%) and FFP (7.9%) were shorter for the nonprosthetic
      step than for the prosthetic step. The BW MoS at initial contact was larger for
      the nonprosthetic step, but because of a significant leg * gait event interaction
      effect, BW MoS did not differ significantly at the end of the double-support
      phase. LIMITATIONS: All participants were relatively good walkers (score of E on
      the Special Interest Group in Amputee Medicine [SIGAM] scale). CONCLUSIONS: The
      smaller step length and FFP of the nonprosthetic step help to create a larger BW
      MoS at initial contact for the nonprosthetic step compared with the prosthetic
      step. Hence, step length asymmetry in people after transtibial amputation might
      be seen as a functional compensation to preserve BW MoS during the double-support
      phase to cope with the limited push-off power of the prosthetic ankle.

PMID- 24903114
TI  - Translating knowledge in rehabilitation: systematic review.
AB  - BACKGROUND: Clinicians are faced with using the current best evidence to make
      treatment decisions, yet synthesis of knowledge translation (KT) strategies that
      influence professional practice behaviors in rehabilitation disciplines remains
      largely unknown. PURPOSE: The purposes of this study were: (1) to examine the
      state of science for KT strategies used in the rehabilitation professions
      (physical therapy, occupational therapy, speech-language pathology), (2) to
      identify the methodological approaches utilized in studies exploring KT
      strategies, and (3) to report the extent that KT interventions are described.
      DATA SOURCES: Eight electronic databases (MEDLINE, CINAHL, ERIC, PASCAL, EMBASE,
      IPA, Scopus, and CENTRAL) were searched from January 1985 to May 2013 using
      language (English) restriction. STUDY SELECTION: Eligibility criteria specified
      articles evaluating interventions or strategies with a primary purpose of
      translating research or enhancing research uptake into clinical practice. DATA
      EXTRACTION: Two reviewers independently screened the titles and abstracts,
      reviewed full-text articles, performed data extraction, and performed quality
      assessment. The published descriptions of the KT interventions were compared with
      the Workgroup for Intervention Development and Evaluation Research's (WIDER)
      Recommendations to Improve the Reporting of the Content of Behaviour Change
      Interventions. DATA SYNTHESIS: Of a total of 2,793 articles located and titles
      and abstracts screened, 26 studies were included in the systematic review.
      Eighteen articles reported interventions that used a multicomponent KT strategy.
      Education-related components were the predominant KT intervention regardless of
      whether it was a single or multicomponent intervention. Few studies used
      reminders or audit and feedback intervention (n=3). Only one study's primary
      outcome measure was an economic evaluation. No clear delineation of the effect on
      KT strategies was seen. LIMITATIONS: Diverse studies were included; however, the
      heterogeneity of the studies was not conducive to pooling the data. CONCLUSIONS:
      The modest-to-low methodological quality assessed in the studies underscores the
      gaps in KT strategies used in rehabilitation and highlights the need for
      rigorously designed studies that are well reported.

PMID- 24903116
TI  - Postural complexity influences development in infants born preterm with brain
      injury: relating perception-action theory to 3 cases.
AB  - BACKGROUND AND PURPOSE: Perception-action theory suggests a cyclical relationship
      between movement and perceptual information. In this case series, changes in
      postural complexity were used to quantify an infant's action and perception
      during the development of early motor behaviors. CASE DESCRIPTION: Three infants
      born preterm with periventricular white matter injury were included. OUTCOMES:
      Longitudinal changes in postural complexity (approximate entropy of the center of
      pressure), head control, reaching, and global development, measured with the Test
      of Infant Motor Performance and the Bayley Scales of Infant and Toddler
      Development, were assessed every 0.5 to 3 months during the first year of life.
      All 3 infants demonstrated altered postural complexity and developmental delays.
      However, the timing of the altered postural complexity and the type of delays
      varied among the infants. For infant 1, reduced postural complexity or limited
      action while learning to control her head in the midline position may have
      contributed to her motor delay. However, her ability to adapt her postural
      complexity eventually may have supported her ability to learn from her
      environment, as reflected in her relative cognitive strength. For infant 2,
      limited early postural complexity may have negatively affected his learning
      through action, resulting in cognitive delay. For infant 3, an increase in
      postural complexity above typical levels was associated with declining
      neurological status. DISCUSSION: Postural complexity is proposed as a measure of
      perception and action in the postural control system during the development of
      early behaviors. An optimal, intermediate level of postural complexity supports
      the use of a variety of postural control strategies and enhances the perception
      action cycle. Either excessive or reduced postural complexity may contribute to
      developmental delays in infants born preterm with white matter injury.

PMID- 24903117
TI  - Initiation of movement and energy expenditure in children with developmental
      delay: a case-control study.
AB  - BACKGROUND: Lower levels of physical activity in children with developmental
      delay (DD) usually are attributed to higher energy costs. However, there is no
      evidence that children with DD spend more energy on daily physical activities,
      such as walking. OBJECTIVE: The aim of this study was to compare energy costs
      during walking and movement initiation times in children with DD and children
      with typical development (TD) and matched for age. DESIGN: This was a case
      control study. METHODS: Children who were 3 and 5 years old and had DD (n=12) or
      TD (n=12) participated in the study. Measurements included ranges of motion in
      the lower extremities, physiological costs of walking, and movement initiation
      times. A task designed to evaluate the initiation of movement (the "go play with
      the toy" task) was used to examine the reaction times for children's goal
      directed walking. RESULTS: The physiological costs of walking were similar in the
      2 groups; however, children with DD walked at a lower speed than children with
      TD. Importantly, children with DD took more time to initiate goal-directed
      walking. LIMITATIONS: The nature of the study design limited causal inference
      from the results. CONCLUSIONS: Children who were 3 to 5 years old and had DD had
      delays in goal-directed movement that may not have been attributable to motor
      impairments. The findings suggest that therapists should evaluate the movement
      initiation ability of 3- to 5-year-old children with DD as part of the design of
      an overall intervention plan.

PMID- 24903118
TI  - Variability in postural control with and without balance-based torso- weighting
      in people with multiple sclerosis and healthy controls.
AB  - BACKGROUND: People with multiple sclerosis (MS) have diminished postural control,
      and center of pressure (COP) displacement varies more in this population than in
      healthy controls. Balance-based torso-weighting (BBTW) can improve clinical
      balance and mobility in people with MS, and exploration using both linear and
      nonlinear measures of COP may help determine whether BBTW optimizes movement
      variability. OBJECTIVE: The aim of this study was to investigate the effects of
      BBTW on people with MS and healthy controls during quiet standing. DESIGN: This
      was a quasi-experimental study comparing COP variability between groups, between
      eye closure conditions, and between weighting conditions in the anterior
      posterior and medial-lateral directions. METHODS: Twenty participants with MS and
      18 healthy controls stood on a forceplate in 4 conditions: eyes open and closed
      and with and without BBTW. Linear measures of COP displacement included range and
      root mean square (RMS). Nonlinear measures included approximate entropy (ApEn)
      and Lyapunov exponent (LyE). Three-way repeated-measures analyses of variance
      compared measures across groups and conditions. The association between weighting
      response and baseline nonlinear variables was examined. When significant
      associations were found, MS subgroups were created and compared. RESULTS: The MS
      and control groups had significantly different range, RMS, and ApEn values. The
      eyes-open and eyes-closed conditions had significantly different range and RMS
      values. Change with weighting correlated with LyE (r=-.70) and ApEn (r=-.59). Two
      MS subgroups, with low and high baseline LyE values, responded to BBTW in
      opposite directions, with a significant main effect for weighting condition for
      the LyE variable in the medial-lateral direction. LIMITATIONS: The small samples
      and no identification of impairments related to LyE at baseline were limitations
      of the study. CONCLUSIONS: The LyE may help differentiate subgroups who respond
      differently to BBTW. In both subgroups, LyE values moved toward the average of
      healthy controls, suggesting that BBTW may help optimize movement variability in
      people with MS.

PMID- 24903119
TI  - Microscopically-tuned band structure of epitaxial graphene through interface and
      stacking variations using Si substrate microfabrication.
AB  - Graphene exhibits unusual electronic properties, caused by a linear band
      structure near the Dirac point. This band structure is determined by the stacking
      sequence in graphene multilayers. Here we present a novel method of
      microscopically controlling the band structure. This is achieved by epitaxy of
      graphene on 3C-SiC(111) and 3C-SiC(100) thin films grown on a 3D microfabricated
      Si(100) substrate (3D-GOS (graphene on silicon)) by anisotropic etching, which
      produces Si(111) microfacets as well as major Si(100) microterraces. We show that
      tuning of the interface between the graphene and the 3C-SiC microfacets enables
      microscopic control of stacking and ultimately of the band structure of 3D-GOS,
      which is typified by the selective emergence of semiconducting and metallic
      behaviours on the (111) and (100) portions, respectively. The use of 3D-GOS is
      thus effective in microscopically unlocking various potentials of graphene
      depending on the application target, such as electronic or photonic devices. 

PMID- 24903121
TI  - A Review and Meta-analysis of Colorectal Cancer Utilities.
AB  - OBJECTIVE: To perform a systematic review of utility weights for colorectal
      cancer (CRC) health states reported in the scientific literature and to determine
      the effects of disease factors, patient characteristics, and utility methods on
      utility values. METHODS: We identified 26 articles written in English and
      published from January 1980 to January 2013, providing 351 unique utilities for
      CRC health states elicited from 6546 unique respondents. The CRC utility data
      were analyzed using linear mixed-effects models with CRC type, stage, time to or
      from initial care, utility measurement instrument, and administration method as
      independent variables. RESULTS: In the base case model, the estimated utility for
      a patient with stage I to III CRC more than 1 year after surgery, rated using a
      self-administered time tradeoff instrument, was 0.90. Stage, time to or from
      initial care, and utility measurement instrument were associated with
      statistically significant utility differences ranging from -0.19 to 0.02.
      Utilities for patients with stage IV cancer were 0.19 lower (P < 0.001) than for
      those with stage I to III cancer. Utilities elicited at more than 1 year after
      surgery were 0.05 higher than those elicited at 3 months after surgery (P =
      0.008). Estimates of differences between utility measurement instruments were
      sensitive to how repeated scores in the same patient group were treated, and
      other findings were sensitive to how the disease stage was modeled and method of
      administration. CONCLUSIONS: Variations in reported utilities are associated with
      factors such as cancer stage, time to or from initial care, and utility
      measurement instrument. More research is needed to study why apparently similar
      patients report different quality of life.

PMID- 24903120
TI  - Brain areas associated with force steadiness and intensity during isometric ankle
      dorsiflexion in men and women.
AB  - Although maintenance of steady contractions is required for many daily tasks,
      there is little understanding of brain areas that modulate lower limb force
      accuracy. Functional magnetic resonance imaging was used to determine brain areas
      associated with steadiness and force during static (isometric) lower limb target
      matching contractions at low and high intensities. Fourteen young adults (6 men
      and 8 women; 27.1 +/- 9.1 years) performed three sets of 16-s isometric
      contractions with the ankle dorsiflexor muscles at 10, 30, 50, and 70 % of
      maximal voluntary contraction (MVC). Percent signal changes (PSCs, %) of the
      blood oxygenation level-dependent response were extracted for each contraction
      using region of interest analysis. Mean PSC increased with contraction intensity
      in the contralateral primary motor area (M1), supplementary motor area, putamen,
      pallidum cingulate cortex, and ipsilateral cerebellum (p < 0.05). The amplitude
      of force fluctuations (standard deviation, SD) increased from 10 to 70 % MVC but
      relative to the mean force (coefficient of variation, CV %) was greatest at 10 %
      MVC. The CV of force was associated with PSC in the ipsilateral parietal lobule
      (r = -0.28), putamen (r = -0.29), insula (r = -0.33), and contralateral superior
      frontal gyrus (r = -0.33, p < 0.05). There were minimal sex differences in brain
      activation across the isometric motor tasks indicating men and women were
      similarly motivated and able to activate cortical motor centers during static
      tasks. Control of steady lower limb contractions involves cortical and
      subcortical motor areas in both men and women and provides insight into key areas
      for potential cortical plasticity with impaired or enhanced leg function.

PMID- 24903122
TI  - Decision aid influences on factors associated with patient empowerment prior to
      cancer treatment decision making.
AB  - BACKGROUND: Despite progress, models that incorporate antecedent and mediating
      factors associated with shared decision making (SDM)-related outcomes remain
      limited. An experimental study tests patient decision aid (DA) effects on a
      network of antecedents and mediators associated with patient empowerment prior to
      a medical decision-making consultation regarding cancer treatment. METHODS: A
      pilot study initially evaluated measurement scales, model fit, and the overall
      effect of the DA experience. The pilot compared matched treatment and control
      group samples of US adult online panel members exposed to a vignette about
      meeting their dermatologist to decide on skin cancer treatment. The treatment
      group also experienced a skin cancer DA with treatment options and value
      clarification activity, while the control group did not. The main study employed
      a randomized experimental design to formally test hypothesized path coefficients
      across the groups. RESULTS: The pilot study suggested an overall enhanced DA
      effect on self-empowerment. In the experimental study, the DA experience
      strengthened the direct path from desire for medical information to self
      empowerment and the indirect path from comprehension/participation confidence to
      self-empowerment through cancer attitude. The DA had no strengthening effect on
      the direct path from life satisfaction to self-empowerment, but in the DA
      condition, the factor appeared to play a role by contributing to the enhanced
      association between confidence and cancer attitude. CONCLUSION: Evidence from
      this research indicates that experiencing a DA prior to treatment decision making
      affects patient empowerment through a network that includes desire for
      information, life satisfaction, and multiple mediators. The studies also
      demonstrate the role that theory-based, multigroup structural equation modeling
      (SEM) can play in increasing understanding of DA effects. Such understanding is
      critical to improving SDM between patients and their physicians.

PMID- 24903123
TI  - A prospective audit of emergency urology activity in a university teaching
      hospital.
AB  - INTRODUCTION: Urology cover is commonly available out-of-hours in most teaching
      hospitals. However, increased pressure to reduce hospital expenditure has forced
      many institutions to consider removing middle grade cover outside of normal
      working hours. The aim of this study was to audit the emergency urology activity
      in our institution over a 12-month period. METHODS: A prospective logbook was
      maintained for all urology referrals from the emergency department between August
      2012 and March 2013. The diagnosis and patient outcome was recorded for each
      referral. The emergency theatre logbook was retrospectively evaluated for all
      emergency urology procedures carried out over the same time period. A basic cost
      analysis was performed to calculate the cost of providing the on-call service.
      RESULTS: A total of 752 patients were referred to the urology service over a 12
      month period. The most common reasons for referral were renal colic and scrotal
      pain. Approximately 41 % of referrals were discharged directly from the emergency
      department. There were 167 emergency operations performed in total. The majority
      of emergency operations and referrals from the emergency department took place
      outside of normal working hours. A basic cost analysis revealed an associated
      cost saving of ?58,120. CONCLUSION: Emergency urology activity constitutes a
      large proportion of the workload at our institution. Restricting emergency
      urology cover would limit essential training opportunities for urology trainees,
      increases length of stay and delay treatment of urological emergencies. Urology
      "out of hours" cover is a cost-efficient method of service provision.

PMID- 24903124
TI  - Intraoperative laser-assisted indocyanine green imaging for objective measurement
      of the vascular delay technique in locoregional head and neck flaps.
AB  - IMPORTANCE: Reconstruction of oncologic or traumatic head and neck defects often
      requires complex planning of locoregional, pedicled, or interpolated flaps. In
      cases with a higher risk of flap failure, vascular delay with staged
      reconstruction can help improve tissue perfusion and increase chances of flap
      survival. An objective tool is needed to help guide reconstructive surgeons with
      the intraoperative decision to pursue vascular delay. OBJECTIVES: To describe a
      pilot study using a novel application of a technique that quantifies and
      validates the benefit of the vascular delay procedure in locoregional flaps and
      to demonstrate a practical and broadly applicable technology that can be easily
      incorporated into intraoperative decision making and improve outcomes for high
      risk flaps. DESIGN, SETTING, AND PARTICIPANTS: A pilot study using intraoperative
      laser-assisted indocyanine green imaging measurements and fluorescence videos to
      objectively measure the benefit of vascular delay procedures in patients with
      head and neck defects and wound healing risk factors requiring locoregional flap
      reconstruction at an academic tertiary care center. MAIN OUTCOMES AND MEASURES:
      Intraoperative laser-assisted indocyanine green imaging with video documentation
      and quantitative measurements was used to evaluate flap perfusion before a
      vascular delay procedure. Measurements were repeated after a 3-week vascular
      delay procedure. RESULTS: Two patients were identified based on comorbid
      conditions that resulted in a higher risk of flap failure, as well as the need
      for a locoregional flap for reconstruction. At the initial elevation of the flap,
      quantitative results from flap imaging demonstrated low perfusion numbers and
      minimal fluorescence, suggesting poor tissue perfusion and increased likelihood
      of postoperative flap compromise or failure. Following a vascular delay of 3
      weeks, repeat measurements were substantially improved. No wound healing issues
      were observed. CONCLUSIONS AND RELEVANCE: This is the first study to date to
      quantitatively demonstrate the benefit of the vascular delay technique in
      patients with potential vascular compromise in locoregional head and neck flap
      reconstruction. Data obtained suggest that this technology can be used to guide
      intraoperative decision making in complicated reconstructions and help optimize
      patient outcomes. LEVEL OF EVIDENCE: NA.

PMID- 24903125
TI  - Multiscale fluid-structure interaction modelling to determine the mechanical
      stimulation of bone cells in a tissue engineered scaffold.
AB  - Recent studies have shown that mechanical stimulation, by means of flow perfusion
      and mechanical compression (or stretching), enhances osteogenic differentiation
      of mesenchymal stem cells and bone cells within biomaterial scaffolds in vitro.
      However, the precise mechanisms by which such stimulation enhances bone
      regeneration is not yet fully understood. Previous computational studies have
      sought to characterise the mechanical stimulation on cells within biomaterial
      scaffolds using either computational fluid dynamics or finite element (FE)
      approaches. However, the physical environment within a scaffold under perfusion
      is extremely complex and requires a multiscale and multiphysics approach to study
      the mechanical stimulation of cells. In this study, we seek to determine the
      mechanical stimulation of osteoblasts seeded in a biomaterial scaffold under flow
      perfusion and mechanical compression using multiscale modelling by two-way fluid
      structure interaction and FE approaches. The mechanical stimulation, in terms of
      wall shear stress (WSS) and strain in osteoblasts, is quantified at different
      locations within the scaffold for cells of different attachment morphologies
      (attached, bridged). The results show that 75.4 % of scaffold surface has a WSS
      of 0.1-10 mPa, which indicates the likelihood of bone cell differentiation at
      these locations. For attached and bridged osteoblasts, the maximum strains are
      397 and 177,200 MUepsilon, respectively. Additionally, the results from
      mechanical compression show that attached cells are more stimulated (maximum
      strain = 22,600 MUepsilon) than bridged cells (maximum strain = 10.000
      MUepsilon)Such information is important for understanding the biological response
      of osteoblasts under in vitro stimulation. Finally, a combination of perfusion
      and compression of a tissue engineering scaffold is suggested for osteogenic
      differentiation.

PMID- 24903127
TI  - Experimental determination of ground and excited state dipole moments of N, N-bis
      (2, 5-di-tert-butylphenyl)-3, 4:9, 10-perylenebis (dicarboximide) (DBPI) a
      photostable laser dye.
AB  - In the present work, the absorption, emission spectra and dipole moments(MU(g),
      MU(e)) of N, N-bis (2, 5-di-tert-butylphenyl)-3, 4:9, 10- perylenebis
      (dicarboximide) (DBPI) have been studied in solvents of various polarities at
      room temperature. Using the methods of solvatochromism, the difference between
      the first excited singlet state (MU(e)) and ground state (MU(g)) dipole moments
      was estimated from Lippert - Mataga,, Bakhshiev, Kawski - Chamma - Viallet
      equations. The change in dipole moment (DeltaMU) was also calculated using the
      variation of the Stokes shift with microscopic solvent polarity parameter
      (E(T)(N)). It was observed that the value of excited singlet state dipole moment
      is higher (3.53 Debye) than the ground state one (1.92Debye), showing that the
      excited state of DBPI is more polar than the ground state.

PMID- 24903126
TI  - Scientometric trends and knowledge maps of global health systems research.
AB  - BACKGROUND: In the last few decades, health systems research (HSR) has garnered
      much attention with a rapid increase in the related literature. This study aims
      to review and evaluate the global progress in HSR and assess the current
      quantitative trends. METHODS: Based on data from the Web of Science database,
      scientometric methods and knowledge visualization techniques were applied to
      evaluate global scientific production and develop trends of HSR from 1900 to
      2012. RESULTS: HSR has increased rapidly over the past 20 years. Currently, there
      are 28,787 research articles published in 3,674 journals that are listed in 140
      Web of Science subject categories. The research in this field has mainly focused
      on public, environmental and occupational health (6,178, 21.46%), health care
      sciences and services (5,840, 20.29%), and general and internal medicine (3,783,
      13.14%). The top 10 journals had published 2,969 (10.31%) articles and received
      5,229 local citations and 40,271 global citations. The top 20 authors together
      contributed 628 papers, which accounted for a 2.18% share in the cumulative
      worldwide publications. The most productive author was McKee, from the London
      School of Hygiene & Tropical Medicine, with 48 articles. In addition, USA and
      American institutions ranked the first in health system research productivity,
      with high citation times, followed by the UK and Canada. CONCLUSIONS: HSR is an
      interdisciplinary area. Organization for Economic Co-operation and Development
      countries showed they are the leading nations in HSR. Meanwhile, American and
      Canadian institutions and the World Health Organization play a dominant role in
      the production, collaboration, and citation of high quality articles. Moreover,
      health policy and analysis research, health systems and sub-systems research,
      healthcare and services research, health, epidemiology and economics of
      communicable and non-communicable diseases, primary care research, health
      economics and health costs, and pharmacy of hospital have been identified as the
      mainstream topics in HSR fields. These findings will provide evidence of the
      current status and trends in HSR all over the world, as well as clues to the
      impact of this popular topic; thus, helping scientific researchers and policy
      makers understand the panorama of HSR and predict the dynamic directions of
      research.

PMID- 24903128
TI  - Characterization and differentiation of body fluids, putrefaction fluid, and
      blood using Hounsfield unit in postmortem CT.
AB  - The purpose of the present study was to evaluate the ranges of Hounsfield unit
      (HU) found in body fluids, putrefaction fluids, and blood on postmortem CT and
      how these ranges are affected by postmortem interval, temperatures, and CT beam
      energy. Body fluids, putrefaction fluids, and blood from a total of 53 corpses
      were analyzed to determine the ranges of HU values from postmortem CT images that
      were taken prior to autopsy. The fluids measured in CT images were obtained at
      autopsy and examined in terms of macroscopic and microscopic appearances. Body
      fluids and blood were also collected in plastic bottles, which were subjected to
      CT scans at different beam energies (80-130 kV) and at various fluid temperatures
      (4 to 40  degrees C). At a postmortem interval of 1 to 4 days, the ranges of HU
      values of the serous fluids (13-38 HU) and the nonsedimented blood (40-88 HU) did
      not overlap. In the sedimented blood, the upper serum layer exhibited HU value
      ranges that overlapped with those of the serous fluids. The putrefaction fluids
      exhibited a range of HU values between 80 and -130 HU. Elevated HU values were
      observed in fluids with accretive cell impurities. HU values decreased slightly
      with increasing temperature and CT beam energy. We concluded that serous fluids
      and blood in fresh corpses can be characterized and differentiated from each
      other based on HU value ranges. In contrast, body fluids in decomposed corpses
      cannot be differentiated by their HU value ranges. Different beam energies and
      corpse temperatures had only minor influences on HU value ranges and therefore
      should not be obstacles to the differentiation and characterization of body
      fluids and blood.

PMID- 24903129
TI  - Developing a mentorship program for psychiatry residents.
AB  - OBJECTIVE: The authors sought to evaluate a formal mentorship program for second
      year psychiatry residents at the University of Toronto after the program's first
      year of implementation. METHODS: Ten mentees and ten faculty mentors were
      interviewed by fellow second-year residents and an independent researcher,
      respectively, about their experiences in the program. Interview data were
      thematically coded and analyzed using a grounded theory approach. RESULTS: Three
      major themes were identified. First, participants emphasized the importance of a
      natural, flexible, and engaging matching process for mentors and mentees. Many
      experienced the random assignment approach to matching and the mandatory nature
      of the program as barriers to developing a meaningful relationship with their
      mentors. Second, participants expressed a preference for geographic proximity
      between mentor and mentee workplaces and for meetings to take place in informal
      settings in order to improve the quality and quantity of their interactions.
      Lastly, participants felt that clear directions and expectations about the
      program's goals should be communicated, and that a forum for information sharing
      among mentors was needed. CONCLUSIONS: Overall, the majority of participants
      believed that the program facilitated growth and development and provided
      positive opportunities for both mentors and mentees. While challenges were
      present in the program, participants provided tangible recommendations to improve
      the process.

PMID- 24903130
TI  - An assessment of attitudes towards people with mental illness among medical
      students and physicians in Ibadan, Nigeria.
AB  - OBJECTIVE: The authors surveyed attitudes towards mental illness among Nigerian
      medical personnel at three different levels of training and experience: medical
      students who had not completed their psychiatry rotation, medical students who
      had competed their psychiatry rotation, and graduate physicians. METHODS: Six
      questions addressed beliefs about the effectiveness of treatments for four
      specific mental illnesses (schizophrenia, bipolar disorder, depression, and
      anxiety) and two medical illnesses (diabetes and hypertension) among the three
      groups. A self-report questionnaire including 56 dichotomous items was used to
      compare beliefs about and attitudes towards people with mental illness. Factor
      analysis was used to identify key attitudes and analysis of covariance (ANCOVA)
      was used to compare the groups adjusting for age and personal experience with
      people with mental illness. RESULTS: There were no significant trends in
      attitudes towards the effectiveness of medication. Exploratory factor analysis of
      the beliefs and attitudes items identified four factors: (1) comfort socializing
      with people with mental, illness; (2) non-superstitious beliefs about the causes
      of mental illness; (3) neighborly feelings towards people with mental illness;
      and (4) belief that stress and abuse are part of the etiology of mental illness.
      ANCOVA comparing attitudes among the three groups showed that on three (1, 2, and
      4) of the four factors medical students who had completed a rotation in
      psychiatry had significantly higher scores than the medical students who had not
      completed a rotation in psychiatry. Graduate physicians showed a similar pattern
      scoring higher than the medical students who had not completed a rotation in
      psychiatry in two factors (1 and 4) but showed no differences from students who
      had completed their psychiatry rotation. CONCLUSION: While beliefs about
      medication effectiveness do not differ between medical trainees and graduate
      professionals, stigmatizing attitudes towards people with mental illness seem to
      be most strongly affected by clinical training. Psychiatric education and
      especially clinical experience result in more progressive attitudes towards
      people with mental illness.

PMID- 24903132
TI  - Researchers find no clear link between air pollution and heart attack or strokes.

PMID- 24903131
TI  - Efficacy of nebulised budesonide versus oral prednisolone in acute severe asthma.
AB  - OBJECTIVE: To compare the efficacy of nebulised budesonide with that of oral
      prednisone in the treatment of acute severe asthma in children. METHODS: Children
      aged 5-12 y with acute exacerbation of bronchial asthma were included. The study
      (budesonide) group received budesonide respirator solution (800 MUg) at intervals
      of 20 min and a single dose of placebo tablets. The control (prednisolone) group
      received placebo solution at intervals of 20 min and a single dose of oral
      prednisolone (2 mg/kg). Both groups received three doses of nebulised salbutamol
      (0.15 mg/kg). Heart rate, respiratory rate, oxygen saturation, PEFR (Peak
      Expiratory Flow Rate) and fitness for discharge were assessed. RESULTS: Both
      groups showed a progressive decrease in tachycardia with treatment, but it was
      significantly greater in study group (p = 0.0002). There was significant decrease
      in tachypnea and improvement in oxygen saturation in both groups, but the
      difference between the groups (p = 0.334 and p = 0.814 respectively) was not
      significant. There was significant improvement in PEFR values in budesonide group
      (p = 0.024). Both groups showed significant improvement in clinical severity
      scores at the end of 2 h (p < 0.0001). Budesonide group had significantly higher
      proportion of patients fit for discharge at 2 h (based on clinical severity
      scores) (p = 0.0278). CONCLUSIONS: Nebulised budesonide significantly improves
      PEFR levels and fitness for discharge at 2 h when compared to oral prednisolone
      in children between 5 and 12 y with acute severe asthma.

PMID- 24903133
TI  - Dorrell resigns as chairman of health select committee.

PMID- 24903134
TI  - Service redesign should be tested as rigorously as new treatments, NHS chief
      says.

PMID- 24903135
TI  - One of world's poorest countries makes "remarkable" progress on tropical
      diseases, report says.

PMID- 24903136
TI  - [Treatment of type 2 diabetes in elderly patients].
AB  - BACKGROUND: Type 2 diabetes is a disease which occurs more frequently with
      increasing age and is particularly influenced by the lifestyle of those affected
      in addition to a genetic disposition and age-related alterations. AIM: The
      purpose of this article is to discuss the evidence for special characteristics of
      the therapy of type 2 diabetes in elderly patients. MATERIAL AND METHODS: The
      study is based on a literature survey and the guidelines of the"Deutsche Diabetes
      Gesellschaft" (DDG, German Diabetes Society). RESULTS: There is increasingly more
      awareness of diabetes in advanced age not least due to the expected demographic
      changes. The therapeutic options in older patients with diabetes must be assessed
      depending on the achievable targets of therapy and comorbidities, in particular
      limited renal function.

PMID- 24903137
TI  - [Age and osteoporosis. Effects of aging on osteoporosis, the diagnostics and
      therapy].
AB  - BACKGROUND: Osteoporosis is an age-associated disease, which is influenced by
      genetic, epigenetic and environmental factors. AIM: This article examines the
      evidence for specific aspects in osteoporosis diagnosis and management in higher
      age groups. MATERIAL AND METHODS: The study was based on extraction of data from
      literature databases and from the guidelines of the "Dachverband Osteologie"
      (DVO, Governing Body for Osteology). RESULTS: Age is a high risk factor for
      osteoporosis. Vitamin D insufficiency and reduced calcium absorption are common
      in the elderly. Loss of bone and muscle develop in a vicious circle of
      immobilization caused by underlying diseases. In addition deficits in cognition
      and coordination promote falls and fragility fractures. Clinical risk assessment
      including geriatric test batteries is recommended in all women > 70 and men > 80
      years of age. Specific medication is indicated if the 10-year fracture risk
      exceeds 30 %, where in women > 75 and in men > 85 years of age bone density
      measurement can be relinquished. There is good evidence for the efficacy of
      antiosteoporotic medication even for the elderly. Prevention of falls requires
      multimodal management to enhance muscle power and coordination. It is essential
      to improve underlying cardiovascular, pulmonary and neurological diseases while
      critically evaluating the necessity of medication that boosts the risk of falls
      and fractures. There is good evidence for age and disease-adapted exercise
      programs such as Tai-Chi. Treating osteoporosis reduces the fracture risk,
      improves the quality of life, maintains independence and decreases mortality.
      CONCLUSION: Treating osteoporosis in the elderly is strongly recommended.
      Multimodal management and medication according to guidelines can be very
      successful, given that interdisciplinary and geriatric concepts consider the
      specific needs of the elderly population.

PMID- 24903138
TI  - Adaptation of the chronic disease self-management program for cancer survivors:
      feasibility, acceptability, and lessons for implementation.
AB  - Self-management in chronic disease has been shown to improve patient-reported and
      health care-related outcomes. However, relatively little information about its
      utility in cancer survivorship is known. We evaluated the feasibility and
      acceptability of the delivery of an adaptation of the evidence-based Chronic
      Disease Self-management Program (Stanford) called Cancer Thriving and Surviving
      (CTS). Triangulated mixed methods were used to capture baseline characteristics
      and post-program experiences using a combination of closed- and open-ended survey
      items; emergent coding and simple descriptive statistics were used to summarize
      the data. Twenty-seven workshops were delivered by 22 CTS leaders to 244
      participants between August 2011 and January 2013 in a variety of settings (48 %
      community, 30 % health care, 22 % regional/community cancer center). Representing
      a variety of cancer types, about half the participants were 1-3 years post
      diagnosis and 45 % were 4 or more years from diagnosis. Program attendance was
      high with 84 % of participants attending four or more of the six sessions in the
      workshop. Overall, 95 % of the participants were satisfied with the program
      content and leaders, and would recommend the program to friends and family. These
      results confirm the feasibility and acceptability of delivery of a high-fidelity,
      peer-led model for self-management support for cancer survivors. Expansion of the
      CTS represents a powerful tool toward improving health-related outcomes in this
      at-risk population.

PMID- 24903139
TI  - Smartphone Applications for the Clinical Oncologist in UK Practice.
AB  - A number of medical smartphone applications have been developed to assist
      clinical oncology specialists. Concerns have arisen that the information provided
      may not be under sufficient scrutiny. This study aims to analyse the current
      applications available for clinical oncologists in the UK. Applications aimed
      specifically at physician clinical oncologists were searched for on the major
      smartphone operating systems: Apple iOS; Google Android; Microsoft Windows OS;
      and Blackberry OS. All applications were installed and analysed. The applications
      were scrutinised to assess the following information: cost; whether the
      information included was referenced; when the information was last updated; and
      whether they made any reference to UK guidelines. A novel rating score based on
      these criteria was applied to each application. Fifty applications were
      identified: 24 for Apple's iOS; 23 for Google's Android; 2 for Blackberry OS; and
      1 for Windows OS. The categories of applications available were: drug reference;
      journal reference; learning; clinical calculators; decision support; guidelines;
      and dictionaries. Journal reference and guideline applications scored highly on
      our rating system. Drug reference application costs were prohibitive. Learning
      tools were poorly referenced and not up-to-date. Smartphones provide easy access
      to information. There are numerous applications devoted to oncology physicians,
      many of which are free and contain referenced, up-to-date data. The cost and
      quality of drug reference and learning applications have significant scope for
      improvement. A regulatory body is needed to ensure the presence of peer-reviewed,
      validated applications to ensure their reliability. 

PMID- 24903140
TI  - The Evolving Role of Regional Radiation Oncology Societies in Resident Education.
AB  - The goal of this study is to develop insight into how a regional radiation
      oncology organization like the New York Roentgen Society (NYRS) can best assist
      in the education and development of residents. From April to June 2012, an
      electronic survey was sent to all 41 post-graduate year 2-4 radiation oncology
      residents in the New York metropolitan area. Questions were formatted using
      Likert scales (ranging from 1 to 5), and the Friedman and Wilcoxon signed-rank
      tests were used to compare the mean ratings of each answer option. Surveys were
      completed by 34 residents (response rate 83 %). The three highest rated features
      that residents hope to get out of their membership in the NYRS included
      "networking" (mean 4.21), "career mentoring" (mean 4.18), and "education" (mean
      4.15), all of which were rated significantly higher (p < 0.002) than the lowest
      rated "physics boards review" (mean 3.36) and "radiation biology boards review"
      (mean 3.15). The three highest rated types of subject matter for meetings
      included "boards review" (mean 4.03), "debate on a controversial clinical topic"
      (mean 3.97), and a "career mentoring workshop" (mean 3.93), all of which were
      rated significantly higher (p < 0.001) than the lowest rated "lecture on a
      research topic" (mean 2.40) and "lecture on a radiation biology/physics topic"
      (mean 2.07). Residents favor networking, career mentoring, and clinical
      educational content (particularly as it relates to boards review) from their
      regional radiation oncology society. These findings may be applicable to similar
      organizations in other cities, as a guide for future programming.

PMID- 24903141
TI  - Mechanisms of isoform-specific Na/K pump regulation by short- and long-term
      adrenergic activation in rat ventricular myocytes.
AB  - BACKGROUND: Many stressful conditions, including cardiovascular diseases, induce
      long-term elevations in circulating catecholamines, thereby leading to changes of
      the Na/K pump and thus affecting myocardial functions. However, only short-term
      adrenergic regulation of the Na/K pump has been reported. The present study is
      the first investigation of long-term adrenergic regulation of the Na/K pump and
      the potential mechanism. METHODS: After acutely isolated Sprague-Dawley rat
      myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump
      high- (IPH) and low-affinity current (IPL), alpha-isoform mRNA, and alpha-isoform
      protein were examined using patch-clamp, RT-PCR, and Western blotting techniques,
      respectively. RESULTS: After the short-term incubation, isoprenaline reduced the
      IPL through a PKA-dependent pathway that involves alpha1-isoform translocation
      from the membrane to early endosomes, and noradrenaline increased the IPH through
      a PKC-dependent pathway that involves alpha2-isoform translocation from late
      endosomes to the membrane. After long-term incubation, isoprenaline increased the
      IPL, alpha1-isoform mRNA, and alpha1-isoform protein, and noradrenaline reduced
      the IPH, alpha2-isoform mRNA, and alpha1-isoform protein through a PKA-or PKC
      dependent pathway, respectively. CONCLUSIONS: These results suggest that long
      term adrenergic Na/K pump regulation is isoform-specific and negatively feeds
      back on the short-term response. Furthermore, long-term regulation involves
      transcription and translation of the respective alpha-isoform, whereas short-term
      regulation involves the translocation of the available alpha-isoform to the
      plasma membrane.

PMID- 24903142
TI  - Statistics for quantifying heterogeneity in univariate and bivariate meta
      analyses of binary data: the case of meta-analyses of diagnostic accuracy.
AB  - Heterogeneity in diagnostic meta-analyses is common because of the observational
      nature of diagnostic studies and the lack of standardization in the positivity
      criterion (cut-off value) for some tests. So far the unexplained heterogeneity
      across studies has been quantified by either using the I(2) statistic for a
      single parameter (i.e. either the sensitivity or the specificity) or visually
      examining the data in a receiver-operating characteristic space. In this paper,
      we derive improved I(2) statistics measuring heterogeneity for dichotomous
      outcomes, with a focus on diagnostic tests. We show that the currently used
      estimate of the 'typical' within-study variance proposed by Higgins and Thompson
      is not able to properly account for the variability of the within-study variance
      across studies for dichotomous variables. Therefore, when the between-study
      variance is large, the 'typical' within-study variance underestimates the
      expected within-study variance, and the corresponding I(2) is overestimated. We
      propose to use the expected value of the within-study variation in the
      construction of I(2) in cases of univariate and bivariate diagnostic meta
      analyses. For bivariate diagnostic meta-analyses, we derive a bivariate version
      of I(2) that is able to account for the correlation between sensitivity and
      specificity. We illustrate the performance of these new estimators using
      simulated data as well as two real data sets.

PMID- 24903143
TI  - Severe Clostridium difficile infection: incidence and risk factors at a tertiary
      care university hospital in Vienna, Austria.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is the major cause of hospital
      acquired bacterial diarrhoea. The incidence of CDI has been increasing in Canada,
      the US and Europe and severe cases are becoming more common. METHODS: A
      retrospective cohort study investigating all patients with an episode of CDI
      present at the Vienna University Hospital between 01 January 2012 and 31 December
      2012 was conducted. All microbiologically confirmed C. difficile toxin positive
      cases were included, ribotyped and analysed regarding their clinical course.
      RESULTS: A total of 278 patients with CDI were recorded, with an overall CDI
      incidence of 5.23 per 10,000 patients-days. Around 84,5 % (235/278) of CDI cases
      would have been classified as severe CDI according to European Society of
      Clinical Microbiology and Infectious Diseases (ESCMID) if all criteria were used.
      According to Society for Healthcare Epidemiology of America and the Infectious
      Diseases Society of America (SHEA/IDSA) guidelines only 16.5 % (46/278) could be
      classified as severe; with a severe CDI incidence of 4.41 and 0.86 per 10,000
      patient-days, respectively. Multivariate analysis showed only a co-morbidity
      index of >= 3 (p = 0.013) as independent risk factor for severe CDI. No link
      between ribotype 027 and severity or clustering was observed in our study
      population. CONCLUSIONS: Special attention in terms of restrictive antibiotic
      prescription should be given to patients having a Charlson co-morbidity >= 3 at
      the time of hospital admission. SHEA/IDSA guidelines were more accurate than
      ESCMID criteria in predicting severe CDI in our collective, of mostly severely
      ill patients, in a tertiary care hospital setting.

PMID- 24903144
TI  - Porous cube-aggregated Co3O4 microsphere-supported gold nanoparticles for
      oxidation of carbon monoxide and toluene.
AB  - Porous cube-aggregated monodisperse Co3O4 microspheres and their supported gold
      (xAu/Co3O4 microsphere, x=1.6-7.4 wt %) nanoparticles (NPs) were fabricated using
      the glycerol-assisted solvothermal and polyvinyl alcohol-protected reduction
      methods. Physicochemical properties of the materials were characterized by means
      of numerous analytical techniques, and their catalytic activities were evaluated
      for the oxidation of toluene and CO. It is shown that the cubic Co3O4
      microspheres were composed of aggregated cubes with a porous structure. The gold
      NPs with a size of 3.2-3.9 nm were uniformly deposited on the surface of Co3O4
      microspheres. Among the Co3O4 microsphere and xAu/Co3O4 microsphere samples, the
      7.4Au/Co3O4 microspheres performed the best, giving T90 % values (the temperature
      required for achieving a CO or toluene conversion of 90 % at a weight hourly
      space velocity of 20 000 mL g(-1)  h(-1)) of -8 and 250  degrees C for CO and
      toluene oxidation, respectively. In the case of 3.0 vol % water vapor
      introduction, a positive effect on CO oxidation and a small negative effect on
      toluene oxidation were observed over the 7.4Au/Co3O4 microsphere sample. The
      apparent activation energies obtained over the xAu/Co3O4 microsphere samples were
      in the ranges of 40.7-53.6 kJ mol(-1) for toluene oxidation and 21.6-34.6 kJ mol(
      1) for CO oxidation. It is concluded that the higher oxygen adspecies
      concentration, better low-temperature reducibility, and stronger interaction
      between gold NPs and Co3O4 as well as the porous microspherical structure were
      responsible for the excellent catalytic performance of 7.4Au/Co3O4 microsphere.

PMID- 24903146
TI  - Baicalein-nicotinamide cocrystal with enhanced solubility, dissolution, and oral
      bioavailability.
AB  - The purpose of this study was to investigate the effect of preparation methods on
      cocrystallization between baicalein (BE) and nicotinamide (NCT), their
      intermolecular interaction, and to demonstrate that BE-NCT cocrystal can achieve
      the simultaneous enhancement in solubility, dissolution, and oral bioavailability
      of BE. The cocrystals from three preparation methods have the similar
      differential scanning calorimetry thermograms and X-ray powder diffraction
      patterns. Compared with crystalline BE, BE-NCT cocrystal has significantly
      improved the solubility and dissolution of BE. In addition, the cocrystal
      exhibits a 2.49-fold higher peak plasma concentration (Cmax) and 2.80-fold higher
      area under the curve (AUC) in rats. This prominent improvement in oral
      bioavailability is even greater than the previously reported BE nanocrystal. This
      investigation enriched the present understanding of cocrystals on their behavior
      in vitro and in vivo, and built the groundwork for future development of BE as a
      promising compound into efficacious drug products.

PMID- 24903145
TI  - Bears in a forest of gene trees: phylogenetic inference is complicated by
      incomplete lineage sorting and gene flow.
AB  - Ursine bears are a mammalian subfamily that comprises six morphologically and
      ecologically distinct extant species. Previous phylogenetic analyses of
      concatenated nuclear genes could not resolve all relationships among bears, and
      appeared to conflict with the mitochondrial phylogeny. Evolutionary processes
      such as incomplete lineage sorting and introgression can cause gene tree
      discordance and complicate phylogenetic inferences, but are not accounted for in
      phylogenetic analyses of concatenated data. We generated a high-resolution data
      set of autosomal introns from several individuals per species and of Y
      chromosomal markers. Incorporating intraspecific variability in coalescence-based
      phylogenetic and gene flow estimation approaches, we traced the genealogical
      history of individual alleles. Considerable heterogeneity among nuclear loci and
      discordance between nuclear and mitochondrial phylogenies were found. A species
      tree with divergence time estimates indicated that ursine bears diversified
      within less than 2 My. Consistent with a complex branching order within a clade
      of Asian bear species, we identified unidirectional gene flow from Asian black
      into sloth bears. Moreover, gene flow detected from brown into American black
      bears can explain the conflicting placement of the American black bear in
      mitochondrial and nuclear phylogenies. These results highlight that both
      incomplete lineage sorting and introgression are prominent evolutionary forces
      even on time scales up to several million years. Complex evolutionary patterns
      are not adequately captured by strictly bifurcating models, and can only be fully
      understood when analyzing multiple independently inherited loci in a coalescence
      framework. Phylogenetic incongruence among gene trees hence needs to be
      recognized as a biologically meaningful signal. 

PMID- 24903148
TI  - Hypoxia promotes nuclear translocation and transcriptional function in the
      oncogenic tyrosine kinase RON.
AB  - Tumor hypoxia drives metastatic progression, drug resistance, and posttreatment
      relapses, but how cancer cells adapt and evolve in response to hypoxic stress is
      not well understood. In this study, we address this question with the discovery
      that the receptor tyrosine kinase RON translocates into the nucleus of hypoxic
      cancer cells. In response to hypoxia, nuclear RON interacts with the hypoxia
      inducible factor HIF-1alpha in a manner that relies on RON tyrosine kinase
      activity, binding to the c-JUN promoter and activating it. Mechanistic
      investigations revealed unexpectedly that nuclear RON played a more important
      role in activation of the c-JUN promoter than HIF-1alpha, leading to increased
      cell proliferation, survival adaptation, in vitro migration, and tumorigenicity
      under hypoxic conditions. Taken together, our results pointed to a novel function
      for RON as a transcriptional regulator that promotes the survival of cancer cells
      subjected to hypoxia. These results suggest novel implications for the use of
      small-molecule inhibitors or monoclonal antibodies targeting the RON kinase in
      the prevention or treatment of advanced cancer.

PMID- 24903147
TI  - Snail recruits Ring1B to mediate transcriptional repression and cell migration in
      pancreatic cancer cells.
AB  - Transcriptional repressor Snail is a master regulator of epithelial-mesenchymal
      transition (EMT), yet the epigenetic mechanism governing Snail to induce EMT is
      not well understood. Here, we report that in pancreatic ductal adenocarcinoma
      (PDAC), elevated levels of the ubiquitin E3 ligase Ring1B and Snail, along with
      elevated monoubiquitination of H2A at K119 (H2AK119Ub1), are highly correlated
      with poor survival. Mechanistic investigations identified Ring1B as a Snail
      interacting protein and showed that the carboxyl zinc fingers of Snail recruit
      Ring1B and its paralog Ring1A to repress its target promoters. Simultaneous
      depletion of Ring1A and Ring1B in pancreatic cancer cells decreased Snail binding
      to the target chromatin, abolished H2AK119Ub1 modification, and thereby
      compromised Snail-mediated transcriptional repression and cell migration. We
      found that Ring1B and the SNAG-associated chromatin modifier EZH2 formed distinct
      protein complexes with Snail and that EZH2 was required for Snail-Ring1A/B
      recruitment to the target promoter. Collectively, our results unravel an
      epigenetic mechanism underlying transcriptional repression by Snail, suggest
      Ring1A/B as a candidate therapeutic target, and identify H2AK119Ub1 as a
      potential biomarker for PDAC diagnosis and prognosis.

PMID- 24903149
TI  - miRNA-128 suppresses prostate cancer by inhibiting BMI-1 to inhibit tumor
      initiating cells.
AB  - microRNA-128 (miR128) is reduced in prostate cancer relative to normal/benign
      prostate tissues, but causal roles are obscure. Here we show that exogenously
      introduced miR128 suppresses tumor regeneration in multiple prostate cancer
      xenograft models. Cancer stem-like cell (CSC)-associated properties were blocked,
      including holoclone and sphere formation as well as clonogenic survival. Using a
      miR128 sensor to distinguish cells on the basis of miR128 expression, we found
      that miR128-lo cells possessed higher clonal, clonogenic, and tumorigenic
      activities than miR128-hi cells. miR128 targets the stem cell regulatory factors
      BMI-1, NANOG, and TGFBR1, the expression of which we found to vary inversely with
      miR128 expression in prostate cancer stem/progenitor cell populations. In
      particular, we defined BMI-1 as a direct and functionally relevant target of
      miR128 in prostate cancer cells, where these genes were reciprocally expressed
      and exhibited opposing biological functions. Our results define a tumor
      suppressor function for miR128 in prostate cancer by limiting CSC properties
      mediated by BMI-1 and other central stem cell regulators, with potential
      implications for prostate cancer gene therapy.

PMID- 24903150
TI  - Effects of JSOG-6 on protection against bone loss in ovariectomized mice through
      regulation of osteoblast differentiation and osteoclast formation.
AB  - BACKGROUND: JSOG-6 is used as a traditional medicine to relieve the symptoms
      associated with inflammation, rheumatism, and osteoporosis in Korea. In the
      present study, we investigated the effects of JSOG-6 on bone loss prevention both
      in in vitro and in vivo as well as its underlying mechanism of action. METHODS:
      Protection against bone loss was assessed in an ovariectomized (OVX) mouse model.
      Bone microarchitecture was measured using a micro-computed tomography to detect
      the parameters of three-dimensional structure of a trabecular bone. Serum
      biomarkers were also evaluated in an OVX-induced model. Osteoclasts derived from
      mouse bone marrow cells (BMCs) and osteoblastic MC3T3-E1 cells were also employed
      to investigate the mechanism of action. RESULTS: Oral administration of JSOG-6
      significantly increased the bone mineral density (BMD) of the femur in OVX mice
      in vivo. Especially, the reduced Tb.No (trabecular bone number) in the OVX group
      was significantly recovered by JSOG-6 treatment. The serum levels of alkaline
      phosphatase (ALP), osteocalcin, C-terminal telopeptide, and tartrate-resistant
      acid phosphatase, biomarkers of bone resorption, were significantly elevated in
      OVX mice, but JSOG-6 effectively inhibited the increase in OVX mice. JSOG-6 was
      also found to enhance the osteoblastic differentiation and maturation with the
      increase of the density and ALP activity, a marker of osteoblastic
      differentiation, as well as calcium deposition, a marker of osteoblastic
      maturation in MC3T3-E1 cells. The effects of JSOG-6 on osteoblastic
      differentiation were also associated in part with the increase of ALP and OPN
      mRNA expressions and the decrease of RANKL mRNA expression in MC3T3-E1 cells.
      CONCLUSIONS: The findings demonstrate that JSOG-6 induced protection against bone
      loss in OVX mice, and its anti-osteoporotic property might be, in part, a
      function of the stimulation of osteoblast differentiation and the inhibition of
      osteoclast formation. These findings suggest that JSOG-6 might be an applicable
      therapeutic traditional medicine for the regulation of the osteoporotic response.

PMID- 24903152
TI  - KIR3DS1*0130108 isolated using full length sequence-based typing.

PMID- 24903151
TI  - Application of community phylogenetic approaches to understand gene expression:
      differential exploration of venom gene space in predatory marine gastropods.
AB  - BACKGROUND: Predatory marine gastropods of the genus Conus exhibit substantial
      variation in venom composition both within and among species. Apart from
      mechanisms associated with extensive turnover of gene families and rapid
      evolution of genes that encode venom components ('conotoxins'), the evolution of
      distinct conotoxin expression patterns is an additional source of variation that
      may drive interspecific differences in the utilization of species' 'venom gene
      space'. To determine the evolution of expression patterns of venom genes of Conus
      species, we evaluated the expression of A-superfamily conotoxin genes of a set of
      closely related Conus species by comparing recovered transcripts of A-superfamily
      genes that were previously identified from the genomes of these species. We
      modified community phylogenetics approaches to incorporate phylogenetic history
      and disparity of genes and their expression profiles to determine patterns of
      venom gene space utilization. RESULTS: Less than half of the A-superfamily gene
      repertoire of these species is expressed, and only a few orthologous genes are
      coexpressed among species. Species exhibit substantially distinct expression
      strategies, with some expressing sets of closely related loci ('under-dispersed'
      expression of available genes) while others express sets of more disparate genes
      ('over-dispersed' expression). In addition, expressed genes show higher dN/dS
      values than either unexpressed or ancestral genes; this implies that expression
      exposes genes to selection and facilitates rapid evolution of these genes. Few
      recent lineage-specific gene duplicates are expressed simultaneously, suggesting
      that expression divergence among redundant gene copies may be established shortly
      after gene duplication. CONCLUSIONS: Our study demonstrates that venom gene space
      is explored differentially by Conus species, a process that effectively permits
      the independent and rapid evolution of venoms in these species.

PMID- 24903153
TI  - Charge transport in polycrystalline graphene: challenges and opportunities.
AB  - Graphene has attracted significant interest both for exploring fundamental
      science and for a wide range of technological applications. Chemical vapor
      deposition (CVD) is currently the only working approach to grow graphene at wafer
      scale, which is required for industrial applications. Unfortunately, CVD graphene
      is intrinsically polycrystalline, with pristine graphene grains stitched together
      by disordered grain boundaries, which can be either a blessing or a curse. On the
      one hand, grain boundaries are expected to degrade the electrical and mechanical
      properties of polycrystalline graphene, rendering the material undesirable for
      many applications. On the other hand, they exhibit an increased chemical
      reactivity, suggesting their potential application to sensing or as templates for
      synthesis of one-dimensional materials. Therefore, it is important to gain a
      deeper understanding of the structure and properties of graphene grain
      boundaries. Here, we review experimental progress on identification and
      electrical and chemical characterization of graphene grain boundaries. We use
      numerical simulations and transport measurements to demonstrate that electrical
      properties and chemical modification of graphene grain boundaries are strongly
      correlated. This not only provides guidelines for the improvement of graphene
      devices, but also opens a new research area of engineering graphene grain
      boundaries for highly sensitive electro-biochemical devices. 

PMID- 24903154
TI  - Measuring change in depression-related interpretation bias: development and
      validation of a parallel ambiguous scenarios test.
AB  - Depressed mood is associated with making negatively biased interpretations of
      ambiguous everyday events. Experimental modification towards a more optimistic
      interpretation has become a focus of recent research. However, to date, no
      measures exist that have been tested with respect to their psychometric
      properties that justify repeated administration to capture change. We aimed to
      develop and evaluate a pragmatic assessment instrument, consisting of a 30-item
      questionnaire (long version) and two 15-item parallel short versions (A and B).
      Items were generated as ambiguous sentences, reflecting three relevant content
      areas based on Beck's cognitive triad. The sentences were rated for pleasantness,
      and this emotional appraisal task indicates the emotional valence of the
      interpretation. Due to the intention to develop a parallel test version, item
      twins were generated. All three versions of the instrument were found to be
      structurally stable, internally consistent and valid. In line with Beck's
      cognitive triad in depression, confirmatory factor analyses determined a three
      factor solution (i.e. self, experiences and future). Significant correlations
      were found between all scales and depressive mood. The two short versions
      represent the same underlying constructs, share identical psychometric properties
      and possess high parallel-test reliability. This study is the first to evaluate
      and confirm the factorial validity as well as the parallel-test reliability of an
      interpretation bias measure. It is suitable to measure bias modification and has
      therefore great potential for research and clinical practice.

PMID- 24903155
TI  - Improved total variation minimization method for few-view computed tomography
      image reconstruction.
AB  - BACKGROUND: Due to the harmful radiation dose effects for patients, minimizing
      the x-ray exposure risk has been an area of active research in medical computed
      tomography (CT) imaging. In CT, reducing the number of projection views is an
      effective means for reducing dose. The use of fewer projection views can also
      lead to a reduced imaging time and minimizing potential motion artifacts.
      However, conventional CT image reconstruction methods will appears prominent
      streak artifacts for few-view data. Inspired by the compressive sampling (CS)
      theory, iterative CT reconstruction algorithms have been developed and generated
      impressive results. METHOD: In this paper, we propose a few-view adaptive prior
      image total variation (API-TV) algorithm for CT image reconstruction. The prior
      image reconstructed by a conventional analytic algorithm such as filtered
      backprojection (FBP) algorithm from densely angular-sampled projections. RESULTS:
      To validate and evaluate the performance of the proposed algorithm, we carried
      out quantitative evaluation studies in computer simulation and physical
      experiment. CONCLUSION: The results show that the API-TV algorithm can yield
      images with quality comparable to that obtained with existing algorithms.

PMID- 24903156
TI  - Repeatability of self-report measures of physical activity, sedentary and travel
      behaviour in Hong Kong adolescents for the iHealt(H) and IPEN - Adolescent
      studies.
AB  - BACKGROUND: Physical activity and sedentary behaviour are important contributors
      to adolescents' health. These behaviours may be affected by the school and
      neighbourhood built environments. However, current evidence on such effects is
      mainly limited to Western countries. The International Physical Activity and the
      Environment Network (IPEN)-Adolescent study aims to examine associations of the
      built environment with adolescent physical activity and sedentary behaviour
      across five continents.We report on the repeatability of measures of in-school
      and out-of school physical activity, plus measures of out-of-school sedentary and
      travel behaviours adopted by the IPEN - Adolescent study and adapted for Chinese
      speaking Hong Kong adolescents participating in the international Healthy
      environments and active living in teenagers-(Hong Kong) [iHealt(H)] study, which
      is part of IPEN-Adolescent. METHODS: Items gauging in-school physical activity
      and out-of-school physical activity, and out-of-school sedentary and travel
      behaviours developed for the IPEN - Adolescent study were translated from English
      into Chinese, adapted, and pilot tested. Sixty-eight Chinese-speaking 12-17 year
      old secondary school students (36 boys; 32 girls) residing in areas of Hong Kong
      differing in transport-related walkability were recruited. They self-completed
      the survey items twice, 8-16 days apart. Test-retest reliability was assessed for
      the whole sample and by gender using one-way random effects intra-class
      correlation coefficients (ICC). Test-retest reliability of items with restricted
      variability was assessed using percentage agreement. RESULTS: Overall test-retest
      reliability of items and scales was moderate to excellent (ICC = 0.47-0.92).
      Items with restricted variability in responses had a high percentage agreement
      (92%-100%). Test-retest reliability was similar in girls and boys, with the
      exception of daily hours of homework (reliability higher in girls) and number of
      school-based sports teams or after-school physical activity classes (reliability
      higher in boys). CONCLUSIONS: The translated and adapted self-report measures of
      physical activity, sedentary and travel behaviours used in the iHealt(H) study
      are sufficiently reliable. Levels of reliability are comparable or slightly
      higher than those observed for the original measures.

PMID- 24903159
TI  - Predicting hepatic steatosis and liver fat content in obese children based on
      biochemical parameters and anthropometry.
AB  - BACKGROUND: Predictors of quantitative evaluation of hepatic steatosis and liver
      fat content (LFC) using clinical and laboratory variables available in the
      general practice in the obese children are poorly identified. OBJECTIVE: To build
      predictive models of hepatic steatosis and LFC in obese children based on
      biochemical parameters and anthropometry. METHODS: Hepatic steatosis and LFC were
      determined using proton magnetic resonance spectroscopy in 171 obese children
      aged 5.5-18.0 years. Routine clinical and laboratory parameters were also
      measured in all subjects. Group analysis, univariable correlation analysis, and
      multivariate logistic and linear regression analysis were used to develop a liver
      fat score to identify hepatic steatosis and a liver fat equation to predict LFC
      in each subject. RESULTS: The predictive model of hepatic steatosis in our
      participants based on waist circumference and alanine aminotransferase had an
      area under the receiver operating characteristic curve of 0.959 (95% confidence
      interval: 0.927-0.990). The optimal cut-off value of 0.525 for determining
      hepatic steatosis had sensitivity of 93% and specificity of 90%. A liver fat
      equation was also developed based on the same parameters of hepatic steatosis
      liver fat score, which would be used to calculate the LFC in each individual.
      CONCLUSIONS: The liver fat score and liver fat equation, consisting of routinely
      available variables, may help paediatricians to accurately determine hepatic
      steatosis and LFC in clinical practice, but external validation is needed before
      it can be employed for this purpose.

PMID- 24903158
TI  - Long-term outcome of catheter ablation in atrial fibrillation patients with
      coexistent metabolic syndrome and obstructive sleep apnea: impact of repeat
      procedures versus lifestyle changes.
AB  - INTRODUCTION: Metabolic syndrome (MS) and obstructive sleep apnea (OSA) are well
      known independent risk factors for atrial fibrillation (AF) recurrence. This
      study evaluated ablation outcome in AF patients with coexistent MS and OSA and
      influence of lifestyle modifications (LSM) on arrhythmia recurrence. METHODS AND
      RESULTS: We included 1,257 AF patients undergoing first catheter ablation (30%
      paroxysmal AF). Patients having MS + OSA were classified into Group 1 (n = 126;
      64 +/- 8 years; 76% male). Group 2 (n = 1,131; 62 +/- 11 years; 72% male)
      included those with either MS (n = 431) or OSA (n = 112; no CPAP users) or
      neither of these comorbidities (n = 588). Patients experiencing recurrence after
      first procedure were divided into 2 subgroups; those having sporadic events
      (frequency < 2 months) remained on previously ineffective antiarrhythmic drugs
      (AAD) and aggressive LSM, while those with persistent arrhythmia (incessant or
      >=2 months) underwent repeat ablation. After 34 +/- 8 months of first procedure,
      66 (52%) in Group 1 and 386 (34%) in Group 2 had recurrence (P < 0.001).
      Recurrence rate in only-MS, only-OSA, and without MS/OSA groups were 40%, 38%,
      and 29%, respectively. Patients with MS + OSA experienced substantially higher
      recurrence compared to those with lone MS or OSA (52% vs. 40% vs. 38%; P =
      0.036). Of the 452 patients having recurrence, 250 underwent redo-ablation and
      194 remained on AAD and LSM. At 20 +/- 6 months, 76% of the redo group remained
      arrhythmia-free off AAD whereas 74% of the LSM group were free from recurrence (P
      = 0.71), 33% of which were off AAD. CONCLUSIONS: MS and OSA have additive
      negative effect on arrhythmia recurrence following single procedure. Repeat
      ablation or compliant LSM increase freedom from recurrent AF.

PMID- 24903160
TI  - Metformin prevents LYRM1-induced insulin resistance in 3T3-L1 adipocytes via a
      mitochondrial-dependent mechanism.
AB  - We previously proposed that LYR motif containing 1 (LYRM1)-induced mitochondrial
      reactive oxygen species (ROS) production contributes to obesity-related insulin
      resistance. Metformin inhibits ROS production and promotes mitochondrial
      biogenesis in specific tissues. We assessed the effects of metformin on insulin
      resistance in LYRM1-over-expressing 3T3-L1 adipocytes. Metformin enhanced basal
      and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and
      Akt phosphorylation and ROS levels, and affected the expression of regulators of
      mitochondrial biogenesis in LYRM1-over-expressing adipocytes. Metformin may
      ameliorate LYRM1-induced insulin resistance and mitochondrial dysfunction in part
      via a direct antioxidant effect and in part by activating the adenosine
      monophosphate-activated protein kinase (AMPK)-PGC1/NRFs pathway. 

PMID- 24903157
TI  - A novel 1,2-benzenediamine derivative FC-99 suppresses TLR3 expression and
      ameliorates disease symptoms in a mouse model of sepsis.
AB  - BACKGROUND AND PURPOSE: Sepsis is a clinical condition characterized by
      overwhelming systemic inflammation with high mortality rate and high prevalence,
      but effective treatment is still lacking. Toll-like receptor 3 (TLR3) is an
      endogenous sensor, thought to regulate the amplification of immune response
      during sepsis. Modulators of TLR3 have an advantage in the treatment of sepsis.
      Here, we aimed to explore the mechanism of a monosubstituted 1,2-benzenediamine
      derivative FC-99 {N(1) -[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine}on
      modulating TLR3 expression and its therapeutic potential on mouse model of
      sepsis. EXPERIMENTAL APPROACH: Cells were pretreated with FC-99 followed by
      poly(I:C) or IFN-alpha stimulation; TLR3 and other indicators were assayed.
      Female C57BL/6 mice were subjected to sham or caecal ligation puncture (CLP)
      surgery after i.p. injection of vehicle or FC-99; serum and tissues were
      collected for further experiments. KEY RESULTS: FC-99 suppressed inflammatory
      response induced by poly(I:C) with no effect on cell viability or uptake of
      poly(I:C). FC-99 also inhibited TLR3 expression induced by not only poly(I:C) but
      also by exogenous IFN-alpha. This inhibition of FC-99 was related to the
      poly(I:C)-evoked IRF3/IFN-alpha/JAK/STAT1 signalling pathway. In CLP-induced
      model of sepsis, FC-99 administration decreased mice mortality and serum levels
      of inflammatory factors, attenuated multiple organ dysfunction and enhanced
      bacterial clearance. Accordingly, systemic and local expression of TLR3 was
      reduced by FC-99 in vivo. CONCLUSION AND IMPLICATIONS: FC-99 reversed TLR3
      expression and ameliorate CLP-induced sepsis in mice. Thus, FC-99 will be a
      potential therapeutic candidate for sepsis.

PMID- 24903161
TI  - Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.
AB  - Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a
      high-mortality rate and long-term neurological sequelae, affecting up to 50% of
      survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an
      innate immune response and tryptophan degradation through the kynurenine pathway.
      Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a
      great number of reactions involved in the metabolism of tryptophan, preventing
      the accumulation of neurotoxic intermediates. In the present study, we evaluated
      the effects of vitamin B6 on memory and on brain-derived neurotrophic factor
      (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal
      meningitis. The animals received either 10 uL of artificial cerebral spinal fluid
      (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were
      divided into four groups: control, control treated with vitamin B6, meningitis,
      and meningitis treated with vitamin B6. Ten days after induction, the animals
      were subjected to behavioral tests: open-field task and step-down inhibitory
      avoidance task. In the open-field task, there was a significant reduction in both
      crossing and rearing in the control group, control/B6 group, and meningitis/B6
      group compared with the training session, demonstrating habituation memory.
      However, the meningitis group showed no difference in motor and exploratory
      activity between training and test sessions, demonstrating memory impairment. In
      the step-down inhibitory avoidance task, there was a difference between training
      and test sessions in the control group, control/B6 group, and meningitis/B6
      group, demonstrating aversive memory. In the meningitis group, there was no
      difference between training and test sessions, demonstrating impairment of
      aversive memory. In the hippocampus, BDNF expression decreased in the meningitis
      group when compared to the control group; however, adjuvant treatment with
      vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6
      attenuated the memory impairment in animals subjected to pneumococcal meningitis.

PMID- 24903162
TI  - Brief Communication: Copper suppression of vascular endothelial growth factor
      receptor-2 is involved in the regression of cardiomyocyte hypertrophy.
AB  - Previous studies revealed that copper (Cu)-induced regression of cardiomyocyte
      hypertrophy is associated with enhanced activity in the vascular endothelial
      growth factor receptor-1 (VEGFR-1) signaling pathway. The mechanism by which Cu
      enhances the activity of VEGFR-1 pathway remains to be defined. The present study
      was undertaken to test the hypothesis that Cu enhances the VEGFR-1 signaling
      pathway via suppression of the VEGFR-2 signaling pathway. Primary cultures of
      neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final
      concentration of 100 uM in cultures for 48 h to induce cell hypertrophy. The
      hypertrophic cardiomyocytes were exposed to copper sulfate at a final
      concentration of 5 uM Cu in cultures for 24 h. Western blot analysis showed that
      PE increased the protein levels of both VEGFR-1 and VEGFR-2. Cu supplementation
      significantly reduced the increase in VEGFR-2, but had no effect on the elevation
      of VEGFR-1. Real-time polymerase chain reaction analysis found no difference in
      the mRNA levels between the VEGFR-1 and VEGFR-2 under the conditions defined
      above. This study thus demonstrated that Cu selectively suppressed PE-elevated
      VEGFR-2 levels likely via post-translational regulation, leading to the VEGFR-1
      signaling pathway becoming dominant and thereby regressing cardiomyocyte
      hypertrophy.

PMID- 24903163
TI  - Paraoxonases function as unique protectors against cardiovascular diseases and
      diabetes: Updated experimental and clinical data.
AB  - Paraoxonase (PON) refers to a family of three enzymes, namely PON1, PON2, and
      PON3. PON1 and PON3 are found in circulation bound to high-density lipoprotein,
      whereas PON2 is an intracellular protein. PON1 was first discovered as an enzyme
      to hydrolyze the organophosphate pesticide paraoxon, an activity that both PON2
      and PON3 lack. All three PON enzymes are able to degrade oxidized lipids and
      protect against oxidative stress. PON enzymes also act to suppress inflammation.
      Animal studies show a critical role for PON enzymes, especially PON1 in
      protecting against cardiovascular diseases and related disorders, including
      diabetes and metabolic syndrome. In line with the findings in experimental
      animals, accumulating evidence from clinical research also indicates that PON
      enzymes function as potential protectors in human cardiovascular diseases and
      related disorders. Identification of PON enzymes as important players in
      cardiovascular health will facilitate the development of novel preventive and
      therapeutic modalities targeting PON enzymes to combat cardiovascular diseases
      and related disorders, which collectively constitute the chief contributors to
      the global burden of disease. This review describes the biochemical properties
      and molecular regulation of PON and summarizes the major recent findings on the
      functions of PON in protecting against cardiovascular diseases and related
      disorders.

PMID- 24903166
TI  - Seasonal growth potential of rare lake water bacteria suggest their
      disproportional contribution to carbon fluxes.
AB  - We studied the seasonal growth potential of opportunistic bacterial populations
      in Lake Zurich (Switzerland) by a series of grazer-free dilution culture assays.
      Pronounced shifts in the composition of the bacterial assemblages were observed
      within one doubling of total cell numbers, from initially abundant Actinobacteria
      to other fast-growing microbial lineages. Small populations with growth
      potentials far above community average were detected throughout the year with
      striking seasonal differences in their respective taxonomic affiliations. Members
      of Cytophaga-Flavobacteria (CF) were disproportionally proliferating only during
      phytoplankton blooms in spring and summer, while Beta- and Gammaproteobacteria
      showed superior growth at all other occasions. Growth rates of
      Alphaproteobacteria and esp. Sphingomonadaceae were significantly correlated to
      water temperatures and were far above community average in summer. Within the
      genus Flavobacterium, two species-like populations showed a tendency for fast
      growth in most experiments, while four others were exclusively proliferating
      either during a spring or during a summer phytoplankton bloom. Their high growth
      potentials but low in situ abundances hint at a tight control by bacterivorous
      grazers and at a consequently accelerated carbon flux to higher trophic levels. 

PMID- 24903167
TI  - Winchester surveillance lab shuts a year early.

PMID- 24903165
TI  - Real-time active MR-tracking of metallic stylets in MR-guided radiation therapy.
AB  - PURPOSE: To develop an active MR-tracking system to guide placement of metallic
      devices for radiation therapy. METHODS: An actively tracked metallic stylet for
      brachytherapy was constructed by adding printed-circuit micro-coils to a
      commercial stylet. The coil design was optimized by electromagnetic simulation,
      and has a radio-frequency lobe pattern extending ~5 mm beyond the strong B0
      inhomogeneity region near the metal surface. An MR-tracking sequence with phase
      field dithering was used to overcome residual effects of B0 and B1
      inhomogeneities caused by the metal, as well as from inductive coupling to
      surrounding metallic stylets. The tracking system was integrated with a graphical
      workstation for real-time visualization. The 3 Tesla MRI catheter-insertion
      procedures were tested in phantoms and ex vivo animal tissue, and then performed
      in three patients during interstitial brachytherapy. RESULTS: The tracking system
      provided high-resolution (0.6 * 0.6 * 0.6 mm(3) ) and rapid (16 to 40 frames per
      second, with three to one phase-field dithering directions) catheter localization
      in phantoms, animals, and three gynecologic cancer patients. CONCLUSION: This is
      the first demonstration of active tracking of the shaft of metallic stylet in MR
      guided brachytherapy. It holds the promise of assisting physicians to achieve
      better targeting and improving outcomes in interstitial brachytherapy.

PMID- 24903164
TI  - Systems-level view of cocaine addiction: the interconnection of the immune and
      nervous systems.
AB  - The human body is a complex assembly of physiological systems designed to manage
      the multidirectional transport of both information and nutrients. An intricate
      interplay between the nervous, circulatory, and secretory systems is therefore
      necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and
      eliminate metabolic waste products and toxins. These systems also provide
      vulnerable routes for modification by substances of abuse. Addictive substances
      are, by definition, neurologically active, but as they and their metabolites are
      spread throughout the body via the nervous, circulatory, respiratory and
      digestive systems, there is abundant opportunity for interaction with numerous
      cell and tissue types. Cocaine is one such substance that exerts a broad
      physiological effect. While a great deal of the research concerning addiction has
      addressed the neurological effects of cocaine use, only a few studies have been
      aimed at delineating the role that cocaine plays in various body systems. In this
      paper, we probe the current research regarding cocaine and the immune system, and
      map a systems-level view to outline a broader perspective of the biological
      response to cocaine. Specifically, our overview of the neurological and
      immunomodulatory effects of the drug will allow a broader perspective of the
      biological response to cocaine. The focus of this review is on the connection
      between the nervous and immune systems and the role this connection plays in the
      long-term complications of cocaine use. By describing the multiplicity of these
      connections, we hope to inspire detailed investigations into the immunological
      interplay in cocaine addiction. 

PMID- 24903168
TI  - EFSA assesses current knowledge of Schmallenberg virus.

PMID- 24903169
TI  - Welsh animal health and welfare panel appointed.

PMID- 24903170
TI  - OIE adopts a global control strategy for peste des petits ruminants.

PMID- 24903171
TI  - Getting offenders back on the right track.

PMID- 24903172
TI  - Animal hoarding: not just an animal welfare issue.

PMID- 24903174
TI  - Unusual presentation of S Dublin infection in a calf.

PMID- 24903175
TI  - Lameness in lambs: questions around joint ill.

PMID- 24903176
TI  - Bovine TB controls.

PMID- 24903177
TI  - Bovine TB controls.

PMID- 24903179
TI  - Availability of antivenom for treating adder bites in dogs.

PMID- 24903186
TI  - Microbial groundwater sampling protocol for fecal-rich environments.
AB  - Inherently, confined animal farming operations (CAFOs) and other intense fecal
      rich environments are potential sources of groundwater contamination by enteric
      pathogens. The ubiquity of microbial matter poses unique technical challenges in
      addition to economic constraints when sampling wells in such environments. In
      this paper, we evaluate a groundwater sampling protocol that relies on extended
      purging with a portable submersible stainless steel pump and Teflon((r)) tubing
      as an alternative to equipment sterilization. The protocol allows for collecting
      a large number of samples quickly, relatively inexpensively, and under field
      conditions with limited access to capacity for sterilizing equipment. The
      protocol is tested on CAFO monitoring wells and considers three cross
      contamination sources: equipment, wellbore, and ambient air. For the assessment,
      we use Enterococcus, a ubiquitous fecal indicator bacterium (FIB), in laboratory
      and field tests with spiked and blank samples, and in an extensive, multi-year
      field sampling campaign on 17 wells within 2 CAFOs. The assessment shows that
      extended purging can successfully control for equipment cross-contamination, but
      also controls for significant contamination of the well-head, within the well
      casing and within the immediate aquifer vicinity of the well-screen. Importantly,
      our tests further indicate that Enterococcus is frequently entrained in water
      samples when exposed to ambient air at a CAFO during sample collection. Wellbore
      and air contamination pose separate challenges in the design of groundwater
      monitoring strategies on CAFOs that are not addressed by equipment sterilization,
      but require adequate QA/QC procedures and can be addressed by the proposed
      sampling strategy. 

PMID- 24903187
TI  - Do gynecologists talk about sexual dysfunction with their patients?
AB  - INTRODUCTION: Female sexual problems and dysfunctions have a high prevalence,
      ranging from 12% to 80%, depending on the definition being used, underlying
      comorbidities, and age. Despite the high prevalence, there are only scarce data
      about the approach gynecologists use to address female sexual dysfunction. AIM:
      The aim of this study is to evaluate the approach of Swiss gynecologists to
      addressing sexual problems among their outpatients. METHODS: After a pilot study
      including 56 physicians, a modified 19-item self-administered questionnaire was
      sent to 856 Swiss gynecologists to evaluate their methods of management of
      patients with sexual issues and their attitudes regarding the integration of
      sexual health issues into the gynecological consultation. MAIN OUTCOME MEASURES:
      Besides demographic information, the self-administered questionnaire included
      questions about addressing sexual health as part of consultation routine,
      estimated frequency of symptoms, reasons for not addressing sexuality, clinical
      conditions in which sexuality was addressed, and methods of management of sexual
      problems. RESULTS: Of the 341 responding gynecologists (39.8% response rate),
      40.4% reported having at least brief (at least 1-2 days) of training in sexual
      medicine, 7.9% of the respondents routinely explored sexual issues with more than
      80% of their patients, 28.2% of the respondents offered appointments specifically
      for sexual issues, and 85% proposed referrals to specialized colleagues. Lack of
      motivation for therapy on the part of the patient was mentioned as the most
      common cause for persisting symptoms (63.3%). Dyspareunia was quoted as the
      most/second most prevalent type of female sexual dysfunction by 77.1% of the
      respondents. CONCLUSION: We conclude that among Swiss gynecologists, sexual
      problems are regarded as an important issue in gynecological outpatient care, but
      addressing patients' sexuality is not yet part of routine practice. Swiss
      gynecologists seem to be most likely to consider hormonal changes (although not
      so much those due to oral contraceptives) to necessitate discussion of sexual
      health issues, while psychosocial transitions or stress seem to be considered
      less important.

PMID- 24903188
TI  - Hospital days, hospitalization costs, and inpatient mortality among patients with
      mucormycosis: a retrospective analysis of US hospital discharge data.
AB  - BACKGROUND: Mucormycosis is a rare and potentially fatal fungal infection
      occurring primarily in severely immunosuppressed patients. Because it is so rare,
      reports in the literature are mainly limited to case reports or small case
      series. The aim of this study was to evaluate inpatient mortality, length of stay
      (LOS), and costs among a matched sample of high-risk patients with and without
      mucormycosis in a large nationally representative database. METHODS: We conducted
      a retrospective analysis using the 2003-2010 Healthcare Cost and Utilization
      Project - Nationwide Inpatient Sample (HCUP-NIS). The NIS is a nationally
      representative 20% sample of hospitalizations from acute care United States (US)
      hospitals, with survey weights available to compute national estimates. We
      classified hospitalizations into four mutually exclusive risk categories for
      mucormycosis: A- severely immunocompromised, B- critically ill, C-
      mildly/moderately immunocompromised, D- major surgery or pneumonia. Mucormycosis
      hospitalizations ("cases") were identified by ICD-9-CM code 117.7. Non
      mucormycosis hospitalizations ("non-cases") were propensity-score matched to
      cases 3:1. We examined demographics, clinical characteristics, and hospital
      outcomes (mortality, LOS, costs). Weighted results were reported. RESULTS: From
      319,366,817 total hospitalizations, 5,346 cases were matched to 15,999 non-cases.
      Cases and non-cases did not differ significantly in age (49.6 vs. 49.7 years),
      female sex (40.5% vs. 41.0%), White race (53.3% vs. 55.9%) or high-risk group (A
      49.1% vs. 49.0%, B-20.0% vs. 21.8%, C-25.5% vs. 23.8%, D-5.5% vs. 5.4%). Cases
      experienced significantly higher mortality (22.1% vs. 4.4%, P<0.001), with mean
      LOS and total costs more than 3-fold higher (24.5 vs. 8.0 days and $90,272 vs.
      $25,746; both P<0.001). CONCLUSIONS: In a national hospital database,
      hospitalizations with mucormycosis had significantly higher inpatient mortality,
      LOS, and hospital costs than matched hospitalizations without mucormycosis.
      Findings suggest that interventions to prevent or more effectively treat
      mucormycosis are needed.

PMID- 24903190
TI  - Whole-exome sequencing in an individual with severe global developmental delay
      and intractable epilepsy identifies a novel, de novo GRIN2A mutation.
AB  - We present a 4-year-old girl with profound global developmental delay and
      refractory epilepsy characterized by multiple seizure types (partial complex with
      secondary generalization, tonic, myoclonic, and atypical absence). Her seizure
      semiology did not fit within a specific epileptic syndrome. Despite a broad
      metabolic and genetic workup, a diagnosis was not forthcoming. Whole-exome
      sequencing with a trio analysis (affected child compared to unaffected parents)
      was performed and identified a novel de novo missense mutation in GRIN2A,
      c.2449A>G, p.Met817Val, as the likely cause of the refractory epilepsy and global
      developmental delay. GRIN2A encodes a subunit of N-methyl-d-aspartate (NMDA)
      receptor that mediates excitatory transmission in the central nervous system. A
      significant reduction in the frequency and the duration of her seizures was
      observed after the addition of topiramate over a 10-month period. Further
      prospective studies in additional patients with mutations in GRIN2A will be
      required to optimize seizure management for this rare disorder. This report
      expands the current phenotype associated with GRIN2A mutations.

PMID- 24903191
TI  - Bacterial responses to fluctuations and extremes in temperature and brine
      salinity at the surface of Arctic winter sea ice.
AB  - Wintertime measurements near Barrow, Alaska, showed that bacteria near the
      surface of first-year sea ice and in overlying saline snow experience more
      extreme temperatures and salinities, and wider fluctuations in both parameters,
      than bacteria deeper in the ice. To examine impacts of such conditions on
      bacterial survival, two Arctic isolates with different environmental tolerances
      were subjected to winter-freezing conditions, with and without the presence of
      organic solutes involved in osmoprotection: proline, choline, or glycine betaine.
      Obligate psychrophile Colwellia psychrerythraea strain 34H suffered cell losses
      under all treatments, with maximal loss after 15-day exposure to temperatures
      fluctuating between -7 and -25  degrees C. Osmoprotectants significantly reduced
      the losses, implying that salinity rather than temperature extremes presents the
      greater stress for this organism. In contrast, psychrotolerant Psychrobacter sp.
      strain 7E underwent miniaturization and fragmentation under both fluctuating and
      stable-freezing conditions, with cell numbers increasing in most cases, implying
      a different survival strategy that may include enhanced dispersal. Thus, the
      composition and abundance of the bacterial community that survives in winter sea
      ice may depend on the extent to which overlying snow buffers against extreme
      temperature and salinity conditions and on the availability of solutes that
      mitigate osmotic shock, especially during melting.

PMID- 24903189
TI  - Population pharmacokinetics of imipenem in critically ill patients with suspected
      ventilator-associated pneumonia and evaluation of dosage regimens.
AB  - AIMS: Significant alterations in the pharmacokinetics (PK) of antimicrobials have
      been reported in critically ill patients. We describe PK parameters of imipenem
      in intensive care unit (ICU) patients with suspected ventilator-associated
      pneumonia and evaluate several dosage regimens. METHODS: This French multicentre,
      prospective, open-label study was conducted in ICU patients with a presumptive
      diagnosis of ventilator-associated pneumonia caused by Gram-negative bacilli, who
      empirically received imipenem intravenously every 8 h. Plasma imipenem
      concentrations were measured during the fourth imipenem infusion using six
      samples (trough, 0.5, 1, 2, 5 and 8 h). Data were analysed with a population
      approach using the stochastic approximation expectation maximization algorithm in
      Monolix 4.2. A Monte Carlo simulation was performed to evaluate the following six
      dosage regimens: 500, 750 or 1000 mg with administration every 6 or 8 h. The
      pharmacodynamic target was defined as the probability of achieving a fractional
      time above the minimal inhibitory concentration (MIC) of >40%. RESULTS: Fifty-one
      patients were included in the PK analysis. Imipenem concentration data were best
      described by a two-compartment model with three covariates (creatinine clearance,
      total bodyweight and serum albumin). Estimated clearance (between-subject
      variability) was 13.2 l h(-1) (38%) and estimated central volume 20.4 l (31%). At
      an MIC of 4 MUg ml(-1) , the probability of achieving 40% fractional time > MIC
      was 91.8% for 0.5 h infusions of 750 mg every 6 h, 86.0% for 1000 mg every 8 h
      and 96.9% for 1000 mg every 6 h. CONCLUSIONS: This population PK model accurately
      estimated imipenem concentrations in ICU patients. The simulation showed that for
      these patients, the best dosage regimen of imipenem is 750 mg every 6 h and not
      1000 mg every 8 h.

PMID- 24903192
TI  - Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in
      cervical artery dissection: a meta-analysis.
AB  - BACKGROUND: Cervical artery dissection (CAD) is a recognized cause of ischemic
      stroke. Hyperhomocysteinemia (HHcy), i.e. an elevated concentration of plasma
      homocysteine, is identified as an independent risk factor for stroke prevalence.
      However, an association between HHcy and CAD has so far remained unknown.
      METHODS: A meta-analysis was performed to analyze the association between HHcy
      and CAD as well as the relevance of the C677T polymorphism of
      methylenetetrahydrofolate reductase (MTHFR), the key enzyme in homocysteine
      metabolism during CAD. We searched PubMed and Embase for studies reporting
      homocysteine concentrations or MTHFR genotype frequencies in CAD patients from
      1990 to 2013. Outcomes were extracted from studies meeting the inclusion criteria
      and were subjected to a meta-analysis by the random-effect model. Heterogeneity
      was assessed by the I(2) test. RESULTS: Eight case-control studies with 2,146
      individuals fulfilled the required criteria and were included in the meta
      analysis. HHcy was found to be significantly associated with CAD (pooled
      standardized mean difference: 0.96; 95% confidence interval, CI: 0.42-1.49; p <
      0.01). We also found a significantly increased risk of CAD in individuals with
      the MTHFR C677T polymorphism by both the recessive model (TT vs. CT+CC; odds
      ratio, OR = 1.81; 95% CI: 1.22-2.67; p = 0.003) and the dominant model (TT+CT vs.
      CC; OR = 1.47; 95% CI: 1.08-1.99; p = 0.014). CONCLUSION: Our data suggest
      positive correlations between HHcy and CAD and between the C677T polymorphism of
      MTHFR and CAD.

PMID- 24903194
TI  - The serum level of HMGB1 (high mobility group box 1 protein) is preferentially
      high in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia
      and systemic symptoms.

PMID- 24903193
TI  - Recent advances in DNA assembly technologies.
AB  - DNA assembly is one of the most important foundational technologies for synthetic
      biology and metabolic engineering. Since the development of the restriction
      digestion and ligation method in the early 1970s, a significant amount of effort
      has been devoted to developing better DNA assembly methods with higher
      efficiency, fidelity, and modularity, as well as simpler and faster protocols.
      This review will not only summarize the key DNA assembly methods and their recent
      applications, but also highlight the innovations in assembly schemes and the
      challenges in automating the DNA assembly methods.

PMID- 24903195
TI  - Growth-differentiation factor 15 and osteoprotegerin in acute myocardial
      infarction complicated by cardiogenic shock: a biomarker substudy of the IABP
      SHOCK II-trial.
AB  - AIMS: This study investigates the role of osteoprotegerin (OPG) and growth
      differentiation factor 15 (GDF-15) as predictors of outcome in cardiogenic shock
      (CS) complicating acute myocardial infarction. The novel biomarkers OPG and GDF
      15 have shown prognostic impact in various cardiovascular diseases including
      myocardial infarction. In acute myocardial infarction complicated by CS, the
      diagnostic and prognostic impact of these biomarkers has not been investigated
      yet. OPG and GDF-15 may have additional prognostic impact on early prognosis
      assessment, being potentially useful for decision-making in CS. METHODS AND
      RESULTS: In the randomized Intra-aortic Balloon Pump in cardiogenic Shock II
      (IABP-SHOCK II)-trial, 600 patients with CS complicating acute myocardial
      infarction undergoing early revascularization were assigned to therapy with or
      without IABP. Within a pre-defined substudy, blood samples were collected from
      190 patients during PCI. GDF-15 and OPG serum levels were measured with standard
      enzyme-linked immunosorbent assay kits. Patients with GDF-15 and OPG levels
      greater than the median showed higher rates of death at 30 days by chi(2) testing
      (OPG, 51% vs. 32%, P = 0.01; GDF-15, 52% vs. 31%, P = 0.005) and log rank testing
      [GDF-15, hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.21-2.94; P =
      0.005; OPG, HR 1.74, 95% CI 1.11-2.71; P = 0.01]. Both markers were significantly
      predictive of 30-day mortality in univariable logistic regression analysis. In a
      multivariable logistic stepwise regression model, GDF-15, TIMI (Thrombolysis In
      Myocardial Infarction) flow grade <3 after PCI, age, LVEF, and serum lactate
      remained significant predictors of 30-day mortality. CONCLUSION: GDF-15 on
      admission is a significant independent predictor of short-term mortality in
      infarct-related CS. Trail registration: NCT00491036.

PMID- 24903196
TI  - Life space and mental health: a study of older community-dwelling persons in
      Australia.
AB  - OBJECTIVES: The ability of older people to mobilise within and outside their
      community is dependent on a number of factors. This study explored the
      relationship between spatial mobility and psychological health among older adults
      living in Australia. METHODS: The survey sample consisted of 260 community
      dwelling men and women aged 75-80 years, who returned a postal survey measuring
      spatial mobility (using the Life Space Questionnaire) and psychological health
      (using the SF36 Health Related Quality of Life Profile). From the Life Space
      Questionnaire, participants were given a life-space score and multinomial
      regression was used to explore the potential effect of mental health on life
      space score. RESULTS: The study found a significant association between mental
      health and life space. However, gender, physical functioning, and ability to
      drive were most strongly associated with the extent of life space and spatial
      mobility. Compared to men, older women are more likely to experience less spatial
      mobility and restricted life space, and hence are more vulnerable to social
      isolation. CONCLUSION: Mental health and life space were associated for the older
      people in this study. These findings have important implications for health
      policy and highlight the need to support older persons to maintain independence
      and social networks, and to successfully age in place within their community.
      This study also highlights the utility of the Life Space Questionnaire in terms
      of identifying older persons at risk of poorer mental health.

PMID- 24903197
TI  - Additional benefit of hemostatic sealant in preservation of ovarian reserve
      during laparoscopic ovarian cystectomy: a multi-center, randomized controlled
      trial.
AB  - STUDY QUESTION: Is hemostasis by hemostatic sealant superior to that achieved by
      bipolar coagulation in preserving ovarian reserve in patients undergoing
      laparoscopic ovarian cystectomy? SUMMARY ANSWER: Post-operative ovarian reserve,
      determined by serial serum anti-Mullerian hormone (AMH) levels, was significantly
      less diminished after ovarian hemostasis when hemostatic sealant was used rather
      than bipolar coagulation. WHAT IS KNOWN ALREADY: Hemostasis achieved with bipolar
      coagulation at ovarian bleeding site results in damage to the ovarian reserve.
      STUDY DESIGN, SIZE, DURATION: A prospective, multi-center randomized trial was
      conducted on 100 participants with benign ovarian cysts, between December 2012
      and October 2013. PARTICIPANT/MATERIALS, SETTING, METHODS: Participants were
      randomized to undergo hemostasis by use of either hemostatic sealant (FloSealTM)
      or bipolar coagulation during laparoendoscopic single-site (LESS) ovarian
      cystectomy. The primary end-point was the rate of decline of ovarian reserve
      calculated by measuring serum AMH levels preoperatively and 3 months post
      operatively. MAIN RESULTS AND THE ROLE OF CHANCE: Age, parity, socio-demographic
      variables, preoperative AMH levels, procedures performed and histologic findings
      were similar between the two groups of patients. There were also no differences
      in operative outcomes, such as conversion to other surgical approaches, operative
      time, estimated blood loss, or perioperative complications between the two
      groups. In both study groups, post-operative AMH levels were lower than
      preoperative AMH levels (all P < 0.001). The rate of decline of AMH levels was
      significantly greater in the bipolar coagulation group than the hemostatic
      sealant group (41.2% [IQR, 17.2-54.5%] and 16.1% [IQR, 8.3-44.7%], respectively,
      P = 0.004). LIMITATIONS, REASONS FOR CAUTION: Some caution is warranted because
      other ovarian reserve markers such as serum markers (basal FSH and inhibin-B) or
      sonographic markers were not assessed. WIDER IMPLICATIONS OF THE FINDINGS: The
      present study shows that the use of a hemostatic sealant during laparoscopic
      ovarian cystectomy should be considered, as hemostatic sealant provides the
      additional benefit of preservation of ovarian reserve. STUDY FUNDING/COMPLETING
      OF INTERESTS: This study was supported by the Medical Research Funds from Kangbuk
      Samsung Hospital. No conflict of interest is declared. TRIAL REGISTRATION NUMBER:
      www.clinicaltrials.gov, no. NCT01857466.

PMID- 24903198
TI  - Prolactin is associated with metabolic risk and cortisol in 1007 women with
      polycystic ovary syndrome.
AB  - STUDY QUESTION: Is there an association between prolactin and markers of
      metabolic risk in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Low serum
      prolactin was a metabolic risk marker in PCOS. WHAT IS KNOWN ALREADY: Prolactin
      is routinely measured to exclude endocrine diseases in PCOS. Recent studies have
      suggested that prolactin can be used as a marker for metabolic and cardiovascular
      risk. STUDY DESIGN, SIZE, DURATION: Retrospective cross-sectional study in an
      academic tertiary-care medical center. Data were collected during 1997-2012.
      Premenopausal women (n = 1007) with hirsutism and/or PCOS and 116 healthy, age
      matched controls were included. Prolactin levels were measured in blood samples
      taken in the morning after a minimum of 2 h awakening time. Macroprolactinemia
      was excluded by the precipitation of serum with polyethylene glycol in patients
      with increased prolactin levels. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum
      prolactin levels were measured along with a clinical evaluation (Ferriman-Gallwey
      score, BMI, waist circumference, blood pressure) plus hormone analyses (sex
      hormones, fasting lipids, insulin, glucose), transvaginal ultrasound, and oral
      glucose tolerance (n = 234) and adrenocorticotrophic hormone tests (n = 201). All
      patients had prolactin levels below the upper reference limit (23 ug/l). MAIN
      RESULTS AND THE ROLE OF CHANCE: Prolactin levels were significantly lower in
      patients versus controls; median (quartiles) prolactin levels 7 (5-10) versus 9
      (7-13) ug/l (P < 0.001). In the patient population prolactin levels were
      inversely associated with age, smoking status, waist circumference, total
      cholesterol, triglyceride and low-density lipoprotein (LDL) and positively
      associated with high-density lipoprotein, estradiol, total testosterone,
      dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and cortisol levels. In
      multiple regression analyses, prolactin was inversely associated with LDL and
      positively associated with estradiol, 17-hydroxyprogesterone and cortisol after
      correcting for age, BMI and smoking status in patients with PCOS. LIMITATIONS,
      REASONS FOR CAUTION: The study design was cross-sectional and prospective studies
      are needed to further determine the impact of prolactin levels on cardiovascular
      outcomes. Patients included in the study were relatively lean and only 20 had
      diabetes, which could have affected our findings. In addition, the collection of
      blood samples when estrogen levels were low (follicular phase) could be related
      to the lower levels of prolactin. Furthermore, as prolactin is secreted in a
      pulsatile manner, several measures of prolactin may be needed to further
      investigate associations between prolactin and metabolic risk. WIDER IMPLICATIONS
      OF THE FINDINGS: Our findings of inverse associations between prolactin levels
      and metabolic risk markers are supported by studies in populations of women
      without PCOS. The association between prolactin and adrenal activity should be
      evaluated in future studies. STUDY FUNDING/COMPETING INTERESTS: This research did
      not receive any specific grant from any funding agency in the public, commercial
      or not-for-profit sector. There are no conflicts of interest to declare.

PMID- 24903199
TI  - The monetary value of patient-centred care: results from a discrete choice
      experiment in Dutch fertility care.
AB  - STUDY QUESTION: What are patients and insurers willing to pay for different
      aspects of fertility care, with a particular focus on patient-centredness?
      SUMMARY ANSWER: In fertility care, both patients and health insurers place a high
      value on patient-centred factors, also when taking into account the effectiveness
      of fertility care. WHAT IS KNOWN ALREADY?: The benefit patients derive from
      fertility treatment may arise from several aspects of their care, such as the
      effectiveness, safety or patient-centred factors. Patient-centredness is
      recognized as an important, multi-dimensional concept, including domains on the
      organizational level (e.g. information provision) and on the human level (e.g.
      patient involvement). STUDY DESIGN, SIZE, AND DURATION: We performed a discrete
      choice experiment (DCE) within 32 Dutch fertility clinics and five large health
      insurance companies in the Netherlands. A total of 996 infertile patients who
      underwent at least one treatment cycle for their fertility problem and 84
      healthcare insurers participated in the study which was executed in the summer of
      2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participating patients and
      health insurers completed a DCE about their preferences in fertility care
      regarding the effectiveness, patient-centredness of care and additional costs.
      Logistic regression analysis was subsequently used to determine what both
      patients and health insurers were willing to pay for a one-step increase in
      patient-centred care and 1% higher pregnancy rates. MAIN RESULTS AND THE ROLE OF
      CHANCE: Five hundred and fifty patients (55.2%) and 45 healthcare insurers
      (53.6%) completed the DCE questionnaire. Patients were willing to pay a median
      amount of ?463 for a relevant one-step increase in patient-centred care and ?107
      for 1% increase in pregnancy rates. Healthcare insurers' valuations were lower:
      ?191 for more patient-centred care and ?60 for 1% increase in pregnancy rates.
      The willingness-to-pay values depended on patients' age, patients' ethnicity,
      income, and treatment type and on health insurers' age. LIMITATIONS, REASONS FOR
      CAUTION: An important limitation of a DCE study is that other attributes, that
      were not included in our study, are relevant as well. Therefore, our study
      participants might make other choices in real life compared with our hypothetical
      DCE scenarios. We tried to prevent this potential bias by selecting the most
      important attributes from the literature, using the input of an expert panel and
      performing a pilot study to test the validity of our questionnaire. WIDER
      IMPLICATIONS OF THE FINDINGS: This study emphasizes the importance of patient
      centredness aspects of care for both infertile patients and their insurers.
      Therefore, efforts by policymakers and clinicians to improve these aspects of
      care would increase the overall value patients derive from their fertility
      treatment. Moreover, although insurers placed a lower monetary value on patient
      centredness aspects than patients, it is arguable that insurers' purchasing
      decisions should be guided by patient rather than insurer preferences. Finally,
      given the relatively high monetary value patients place on patient-centred
      aspects of their fertility care, there may be a willingness to allow for some
      optional co-payments for this quality of care dimension. STUDY FUNDING/COMPETING
      INTERESTS: This work was supported by Merck Sharp and Dohme, the Netherlands. No
      competing interests declared. TRIAL REGISTRATION NUMBER: Clinical Trials
      NCT01834313.

PMID- 24903200
TI  - The association of clinical symptoms with deep infiltrating endometriosis: the
      importance of the preoperative clinical assessment.

PMID- 24903201
TI  - A clinical score can predict associated deep infiltrating endometriosis before
      surgery for an endometrioma.
AB  - STUDY QUESTION: Is it possible to detect associated deep infiltrating
      endometriosis (DIE) before surgery for patients operated on for endometriomas
      using a preoperative clinical symptoms questionnaire? SUMMARY ANSWER: A
      diagnostic score of DIE associated with endometriomas using four clinical
      symptoms defined a high-risk group where the probability of DIE was 88% and a low
      risk group with a 10% probability of DIE. WHAT IS KNOWN ALREADY: Many clinical
      symptoms are already known to be associated with DIE but they have not yet been
      used to build a clinical prediction model. STUDY DESIGN, SIZE, DURATION: We built
      a diagnostic score of DIE based on a case control study of 326 consecutive
      patients operated on for an endometrioma between January 2005 and October 2011:
      164 had associated DIE (DIE+) and 162 had no DIE (DIE-). We derived the score on
      a training sample obtained from a random selection of 2/3 of the population (211
      patients, 101 DIE+, 110 DIE-), and validated the results on the remaining third
      (115 patients, 63 DIE+, 52 DIE-). The gold standard for the diagnosis of DIE was
      based on surgical exploration and histological diagnosis. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Participants were consecutive patients aged 18-42 years who
      underwent surgery for an endometrioma with histological confirmation and complete
      treatment of their endometriotic lesions: data for these women were extracted
      from a prospective database including a standardized preoperative questionnaire.
      On the training dataset, variables associated with DIE in a univariate analysis
      were introduced in a multiple logistic regression and selected by a backward
      stepwise procedure and a Jackknife procedure. A diagnostic score of DIE was built
      with the scaled/rounded coefficients of the multiple regression. Two cut-off
      values delimitated a high and a low risk group, and their diagnostic accuracy was
      tested on the validation dataset. MAIN RESULTS AND THE ROLE OF CHANCE: Four
      variables were independently associated with DIE: visual analogue scale of gastro
      intestinal symptoms >=5 or of deep dyspareunia >5 (adjusted diagnostic odds ratio
      (aDOR) = 6.0, 95% confidence interval (CI) [2.9-12.1]), duration of pain greater
      than 24 months (aDOR = 3.8, 95% CI [1.9-7.7]), severe dysmenorrhoea (defined as
      the prescription of the oral contraceptive pill for the treatment of a primary
      dysmenorrhoea or the worsening of a secondary dysmenorrhoea) (aDOR = 3.8, 95% CI
      [1.9-7.6]) and primary or secondary infertility (aDOR = 2.5, 95% CI [1.2-4.9]).
      The sum of these variables weighted by their rounded/scaled coefficients
      constituted the score ranging from 0 to 53. A score <13 defined a low-risk group
      where the probability of DIE was 10% (95% CI [7-15] with a sensitivity of 95%
      (95% CI [89-98]) and a negative likelihood ratio of 0.1 (95% CI [0.0-0.3]). A
      score >=35 defined a high-risk group where the probability of DIE was 88% (95% CI
      [83-92%]), with a specificity of 94% (95% CI [87-97]), and a positive likelihood
      ratio of 8.1 (95% CI [3.9-17.0]). The performance of the score was confirmed on
      the validation dataset with 11% of DIE+ patients having a score <13 (sensibility:
      95%) and 90% of DIE+ patients having a score >=35 (specificity: 94%). LIMITATION,
      REASONS FOR CAUTION: This study was performed in a department specialized in DIE
      management. Score accuracy could be different in less specialized centres. WIDER
      IMPLICATIONS OF THE FINDINGS: This score could have a major clinical impact on
      the time of diagnosis, the management of DIE and could reduce the cost of
      investigations by helping to identify high-risk patients, while preserving the
      quality of care. STUDY FUNDING/COMPETING INTERESTS: The authors have no competing
      interests to declare. No grant supported the study.

PMID- 24903202
TI  - Prognostic models for high and low ovarian responses in controlled ovarian
      stimulation using a GnRH antagonist protocol.
AB  - STUDY QUESTION: Can predictors of low and high ovarian responses be identified in
      patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist
      protocol? SUMMARY ANSWER: Common prognostic factors for high and low ovarian
      responses were female age, antral follicle count (AFC) and basal serum FSH and
      LH. WHAT IS KNOWN ALREADY: Predictors of ovarian response have been identified in
      GnRH agonist protocols. With the introduction of GnRH antagonists to prevent
      premature LH rises during COS, and the gradual shift in use of long GnRH agonist
      to short GnRH antagonist protocols, there is a need for data on the
      predictability of ovarian response in GnRH antagonist cycles. STUDY DESIGN, SIZE,
      DURATION: A retrospective analysis of data from the Engage trial and validation
      with the Xpect trial. Prognostic models were constructed for high (>18 oocytes
      retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was
      based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial.
      Multivariable logistic regression models were constructed in a stepwise fashion
      (P < 0.15 for entry). Validation based on calibration was performed in patients
      with equivalent treatment (n = 199) in the Xpect trial. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Infertile women with an indication for COS prior to IVF. The
      Engage and Xpect trials included patients of similar ethnic origins from North
      America and Europe who had regular menstrual cycles. The main causes of
      infertility were male factor, tubal factor and endometriosis. MAIN RESULTS AND
      THE ROLE OF CHANCE: In the Engage trial, 18.3% of patients had a high and 12.7%
      had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1
      were prognostic for both high and low ovarian responses. Higher AFC and LH were
      associated with an increased chance of high ovarian response. Older age and
      higher FSH correlated with an increased chance of low ovarian response. Region
      (North America/Europe) and BMI were prognostic for high ovarian response, and
      serum estradiol at stimulation Day 1 was associated with low ovarian response.
      The area under the receiver operating characteristic (ROC) curve (AUC) for the
      model for a high ovarian response was 0.82. Sensitivity and specificity were 0.82
      and 0.73; positive and negative predictive values were 0.40 and 0.95,
      respectively. The AUC for the model for a low ovarian response was 0.80.
      Sensitivity and specificity were 0.77 and 0.73, respectively; positive and
      negative predictive values were 0.29 and 0.96, respectively. In Xpect, 19.1% of
      patients were high ovarian responders and 16.1% were low ovarian responders. The
      slope of the calibration line was 0.81 and 1.35 for high and low ovarian
      responses, respectively, both not statistically different from 1.0. In summary,
      common prognostic factors for high and low ovarian responses were female age, AFC
      and basal serum FSH and LH. Simple multivariable models are presented that are
      able to predict both a too low or too high ovarian response in patients treated
      with a GnRH antagonist protocol and daily rFSH. LIMITATIONS, REASONS FOR CAUTION:
      Anti-Mullerian hormone was not included in the prediction modelling. WIDER
      IMPLICATIONS OF THE FINDINGS: The findings will help with the identification of
      patients at risk of a too high or too low ovarian response and individualization
      of COS treatment. STUDY FUNDING/COMPETING INTERESTS: Financial support for this
      study and the editorial work was provided by Merck, Sharp & Dohme Corp. (MSD), a
      subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA. F.J.B. received a
      grant from CVZ to his institution; P.J.M.V. and H.W. are employees of MSD, and
      B.M.J.L.M. was an employee of MSD at the time of development of this manuscript.
      TRIAL REGISTRATION NUMBERS: NCT 00696800 and NCT00778999.

PMID- 24903203
TI  - Scratching beneath 'The Scratching Case': systematic reviews and meta-analyses,
      the back door for evidence-based medicine.
AB  - Endometrial scratching or injury was first suggested a decade ago as a simple
      intervention to improve endometrial receptivity in patients undergoing ART. More
      than a decade later, based on weak evidence some doctors have adopted this
      strategy, although there is not yet agreement about its real benefit. In this
      opinion paper, we analyze the methodological and plausibility problem beneath
      'the Scratching Case'. This is also applicable to several other examples of
      spurious associations reported in the literature. In particular, we emphasize
      what should be done so as not to dilute evidence-based medicine by a vicious
      circle created by the over-exploitation of inadequate or insufficient data to
      compute incorrect or incomplete conclusions. 

PMID- 24903204
TI  - The good, the bad and the ugly: meta-analyses.

PMID- 24903205
TI  - WHI-P154 enhances the chemotherapeutic effect of anticancer agents in ABCG2
      overexpressing cells.
AB  - ATP-binding cassette (ABC) transmembrane proteins evidently decrease the
      intracellular accumulation of substrate chemotherapeutic drugs by extruding them
      against a concentration gradient, thereby inducing drug resistance. Here we
      reported the effect of WHI-P154, an irreversible inhibitor of Janus kinase 3 and
      epidermal growth factor receptor tyrosine kinases, on reversing ABC transporters
      mediated drug resistance. We found that WHI-P154 significantly enhanced the
      sensitivity of ABCG2-overexpressing cells to its substrates. WHI-P154 moderately
      sensitized ABCB1-overexpressing KB-C2 cells to its substrates whereas showed no
      sensitizing effect on ABCC1-, ABCC2 or ABCC10-mediated drug resistance. Moreover,
      WHI-P154 produced a significant increase in the intracellular accumulation of
      [3H]-mitoxantrone in ABCG2-overexpressing cells. The expression levels nor the
      localization of the ABCG2 protein was altered after treatment of ABCG2
      overexpressing cells with WHI-P154. Further studies indicated that WHI-P154
      enhanced the ATPase activity of ABCG2 at low concentrations (<10 MUM).
      Additionally, a docking model predicted the binding conformation of WHI-P154
      within the transmembrane region of homology-modeled human ABCG2 transporter.
      Collectively, these findings highlighted WHI-P154 could significantly reverse
      ABCG2-mediated multidrug drug resistance by directly blocking the efflux
      function.

PMID- 24903206
TI  - Cushing's syndrome in a morbidly obese patient undergoing evaluation before
      bariatric surgery.
AB  - OBJECTIVE: Cushing's syndrome (CS) is extremely rare in morbidly obese patients.
      To date, no occurrences in obese patients with BMI above 60 kg/m2 have been
      reported in the literature. CASE REPORT: This case report describes a patient who
      was admitted to the ward of the Clinical Division of Endocrinology and Metabolism
      of the Medical University of Vienna in preparation for bariatric surgery. The
      patient was a 49-year-old female who showed morbid obesity (BMI 61.6 kg/m2),
      hypertension, and substituted hypothyroidism. Preoperative work-up revealed CS
      due to an adrenal adenoma. Therefore, the patient underwent unilateral
      adrenalectomy followed by bariatric surgery 6 months later. CONCLUSION: Since
      undiagnosed CS might result in severe perioperative complications in a population
      already at increased risk, this case report underlines the importance of careful
      endocrine evaluation of morbidly obese patients. After all, even rare endocrine
      causes should be excluded.

PMID- 24903207
TI  - Recreational football improves bone mineral density and bone turnover marker
      profile in elderly men.
AB  - This study examined the effect of recreational football and resistance training
      on bone mineral density (BMD) and bone turnover markers (BTMs) in elderly men.
      Twenty-six healthy sedentary men (age 68.2 +/- 3.2 years) were randomized into
      three groups: football (F; n = 9) and resistance training (R; n = 9), completing
      45-60 min training two to three times weekly, and inactive controls (C; n = 8).
      Before, after 4 months, and after 12 months, BMD in proximal femur (PF) and whole
      body (WB) were determined together with plasma osteocalcin (OC), procollagen type
      1 amino-terminal propeptide (P1NP), and carboxy-terminal type-1 collagen
      crosslinks (CTX-1). In F, BMD in PF increased up to 1.8% (P < 0.05) from 0 to 4
      months and up to 5.4% (P < 0.001) from 0 to 12 months; WB-BMD remained unchanged.
      After 4 and 12 months of football, OC was 45% and 46% higher (P < 0.001), and
      P1NP was 41% and 40% higher (P < 0.001) than at baseline, respectively. After 12
      months, CTX-1 showed a main effect of 43% (P < 0.05). In R and C, BMD and BTM
      remained unchanged. In conclusion, 4 months of recreational football for elderly
      men had an osteogenic effect, which was further developed after 12 months,
      whereas resistance training had no effect. The anabolic response may be due to
      increased bone turnover, especially improved bone formation.

PMID- 24903208
TI  - Normative data for the repeatable battery for the assessment of
      neuropsychological status in elderly Chinese.
AB  - Asia will experience a surge in dementia prevalence within the next 20-40 years,
      but there is a dearth of well-normed neuropsychological tests that could assist
      with dementia diagnosis. Here, we report normative data for the Repeatable
      Battery for the Assessment of Neuropsychological Status (RBANS) in Elderly ethnic
      Chinese Singaporeans aged 55-91 years of age. A total of 1,165 male and female
      community-dwelling, cognitively normal elderly Chinese persons in Singapore, with
      varying levels of education and range of languages, were tested with the RBANS
      version A. The effects of age, education, language and gender on RBANS
      performance were examined. Negative effects of increased age and positive effects
      of education on the RBANS subtests, Index and Total Scale scores were found
      suggesting differential associations between age-related cognitive decline and
      education that vary according to the specific cognitive ability measured. The
      findings indicate that unique cultural and educational profile of elderly Chinese
      should be considered when applying the RBANS in this population. 

PMID- 24903209
TI  - Is pigment cell pattern formation in zebrafish a game of cops and robbers?

PMID- 24903210
TI  - Anti-carbonic anhydrase II antibodies in end-stage renal disease patients.
AB  - OBJECTIVE: The aim of this study was to investigate the presence of anti-carbonic
      anhydrase (CA II) autoantibodies in patients with end-stage renal disease (ESRD)
      and relationships between the autoantibody titers and ghrelin, glucose, blood
      urea nitrogen (BUN) and creatinine. SUBJECTS AND METHODS: Serum CA II
      autoantibody titers, malondialdehyde (MDA), BUN, creatinine and ghrelin levels
      were measured in 45 ESRD patients and 45 healthy subjects. RESULTS: The CA II
      autoantibody titers in the ESRD group (0.170 +/- 0.237) were significantly higher
      than those in the control group (0.079 +/- 0.032; p = 0.035). MDA and ghrelin
      levels were also significantly higher in the ESRD group (p < 0.001). A weak
      positive correlation was determined between anti-CA II antibody titers and MDA,
      and a negative correlation was observed between ghrelin levels and anti-CA II
      antibody titers (r = 0.287, p = 0.028 and r = -0.278, p = 0.032, respectively).
      CONCLUSIONS: In ESRD patients, the results showed the development of an
      autoimmune response against CA II. This suggests that anti-CA II antibodies could
      be involved in the pathogenesis of ESRD.

PMID- 24903212
TI  - Identification of hemiclonal reproduction in three species of Hexagrammos marine
      reef fishes.
AB  - Natural hybrids between the boreal species Hexagrammos octogrammus and two
      temperate species Hexagrammos agrammus and Hexagrammos otakii were observed
      frequently in southern Hokkaido, Japan. Previous studies revealed that H.
      octogrammus is a maternal ancestor of both hybrids; the hybrids are all fertile
      females and they frequently breed with paternal species. Although such rampant
      hybridization occurs, species boundaries have been maintained in the hybrid zone.
      Possible explanations for the absence of introgressions, despite the frequent
      backcrossing, might include clonal reproduction: parthenogenesis, gynogenesis and
      hybridogenesis. The natural hybrids produced haploid eggs that contained only the
      H. octogrammus genome (maternal ancestor) with discarded paternal genome and
      generated F1 -hybrid type offspring by fertilization with the haploid sperm of H.
      agrammus or H. otakii (paternal ancestor). This reproductive mode was found in an
      artificial backcross hybrid between the natural hybrid and a male of the paternal
      ancestor. These findings indicate that the natural hybrids adopt hybridogenesis
      with high possibility and produce successive generations through hybridogenesis
      by backcrossing with the paternal ancestor. These hybrids of Hexagrammos
      represent the first hybridogenetic system found from marine fishes that widely
      inhabit the North Pacific Ocean. In contrast with other hybridogenetic systems,
      these Hexagrammos hybrids coexist with all three ancestral species in the hybrid
      zone. The coexistence mechanism is also discussed. 

PMID- 24903211
TI  - The roles of Ca2+/NFAT signaling genes in Kawasaki disease: single- and multiple
      risk genetic variants.
AB  - Ca(2+)/nuclear factor of activated T-cells (Ca(2+)/NFAT) signaling pathway may
      play a crucial role in Kawasaki disease (KD). We investigated 16 genetic
      variants, selected by bioinformatics analyses or previous studies, in 7 key genes
      involved in this pathway in a Chinese population. We observed a significantly or
      marginally increased KD risk associated with rs2720378 GC + CC genotypes (OR =
      1.39, 95% CI = 1.07-1.80, P = 0.014) or rs2069762 AC + CC genotypes (OR = 1.28,
      95% CI = 0.98-1.67, P = 0.066), compared with their wild type counterparts. In
      classification and regression tree analysis, individuals carrying the combined
      genotypes of rs2720378 GC or CC genotype, rs2069762 CA or CC genotype and
      rs1561876 AA genotype exhibited the highest KD risk (OR = 2.12, 95% CI = 1.46
      3.07, P < 0.001), compared with the lowest risk carriers of rs2720378 GG
      genotype. Moreover, a significant dose effect was observed among these three
      variants (Ptrend < 0.001). In conclusion, this study implicates that single- and
      multiple-risk genetic variants in this pathway might contribute to KD
      susceptibility. Further studies on more comprehensive single nucleotide
      polymorphisms, different ethnicities and larger sample sizes are warranted, and
      the exact biological mechanisms need to be further clarified. 

PMID- 24903214
TI  - Prevalence of normal liver tests in patients with choledocholithiasis undergoing
      endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND/AIMS: Abnormal liver chemistry tests are a hallmark of common bile
      duct (CBD) stones. There is little information, however, on the prevalence of and
      predictors for normal liver chemistry tests in such patients. METHODS: Over an 11
      year period, all patients undergoing endoscopic retrograde
      cholangiopancreatography (ERCP) at our Center were prospectively identified.
      Patients in this study were those with CBD stones found at ERCP and where the
      indication for ERCP was CBD stones seen on imaging studies or when CBD stones
      were highly suspected based upon clinical presentation and radiographic and
      laboratory findings. Liver chemistry tests were recorded from those taken at the
      time of initial presentation as well as the time closest to ERCP. RESULTS: Of a
      total of 5,133 patients undergoing ERCP during the study period, the indication
      was suspicion for CBD stones or for radiographically identified CBD stones in 476
      and 593, respectively, with 115 patients having both indications. Of these 1184
      patients, 765 had CBD stones of whom 541 had liver tests. Of these 541, 29
      patients (5.4%) were found to consistently have normal liver chemistry tests.
      Multivariate analysis identified two factors predictive of normal liver tests
      including age >55 years and the presence of abdominal pain. CONCLUSIONS: Although
      rare, liver tests can be normal in patients with CBD stones. Patients most likely
      to have normal liver tests included older patients and those with abdominal pain.

PMID- 24903213
TI  - Molecular epidemiology of Porcine torovirus (PToV) in Sichuan Province, China:
      2011-2013.
AB  - BACKGROUND: Porcine torovirus (PToV) is a member of the genus Torovirus which is
      responsible for gastrointestinal disease in both human beings and animals with
      particular prevalence in youth. Torovirus infections are generally asymptomatic,
      however, their presence may worsen disease consequences in concurrent infections
      with other enteric pathogens. METHODS: A total of 872 diarrheic fecal samples
      from pigs of different ages were collected from 12 districts of Sichuan Province
      in the southwest of China. RT-PCR was done with PToV S gene specific primers to
      detect the presence of PToV positive samples. M gene specific primers were used
      with the PToV positive samples and the genes were sequenced. A phylogenetic tree
      was constructed based on the M gene nucleotide sequences from the 19 selected
      novel Sichuan strains and 21 PToV and BToV M gene sequences from GenBank.
      RESULTS: A total of 331 (37.96%, 331/872) samples were found to be positive for
      PToV and the highest prevalence was observed in piglets aged from 1 to 3 weeks
      old. Through phylogenetic inference the 40 PToV M gene containing sequences were
      placed into two genotypes (I & II). The 19 novel Sichuan strains of genotype I
      showed strong correlations to two Korean gene sequences (GU-07-56-11 and GU-07-56
      22). Amino-acid sequence analysis of the 40 PToV M gene strains revealed that the
      M gene protein was highly conserved. CONCLUSIONS: This study uncovered the
      presence of PToV in Sichuan Province, and demonstrated the need for continuous
      surveillance PToV of epidemiology.

PMID- 24903215
TI  - Serum selenium deficiency in patients with hematological malignancies: is a
      supplementation study mandatory?

PMID- 24903216
TI  - Development of an animal model to evaluate the allergenicity of food allergens.
AB  - SCOPE: Considering the increasing numbers of patients suffering from food allergy
      (FA) as well as the great variety of novel foods and food compositions, an unmet
      need exists for the development of preclinical approaches to characterize the
      allergenic potential of proteins. The aim of our study was to evaluate the
      allergenicity of different food allergens in a rat model. METHODS: Brown Norway
      rats were sensitized to protein extracts (RuBisCO, apple, soy, peanut, garden
      pea) or ovalbumin (OVA) combined with Bordetella pertussis and aluminium
      hydroxide, followed by oral allergen challenges. RESULTS: Allergen-specific serum
      immunoglobulin production and the proliferation of mononuclear cells from spleen
      confirmed sensitization. To assess functional alterations in the gut, intestinal
      permeability was measured, which increased in sensitized and challenged animals
      compared to non-sensitized controls. Allergens with high allergenic potential
      (peanut, OVA, soy) caused a stronger immunological response than allergens with
      low allergenic potential, such as RuBisCO and apple. Moreover, the immunological
      responses were reduced when using boiled instead of raw soy and pea proteins.
      CONCLUSION: This model mimics key features of FA and facilitates investigating
      the allergenicity of allergens in novel food or food compositions in vivo.

PMID- 24903217
TI  - Role of the glucose tolerance test as a predictor of preeclampsia.
AB  - OBJECTIVE: To determine whether oral glucose tolerance tests (OGTT) play a role
      as predictors of preeclampsia (PET) in pregnant women. METHODS: A retrospective
      case-control study was conducted in 2,002 singleton pregnancies that had a
      uterine artery (UtA) Doppler at 22-25 weeks and an OGTT. The UtA Doppler and OGTT
      were adjusted based on maternal characteristics, and the results were expressed
      as multiples of the expected normal median and compared between groups. Logistic
      regression analysis was used to determine whether maternal characteristics, OGTT,
      and UtA Doppler significantly contribute to the prediction of early- (<34 weeks),
      intermediate- (34-37 weeks), or late-onset (>37 weeks) PET. The performance of
      the screening was determined by ROC curves. RESULTS: Women who developed PET were
      characterized by an older maternal age, an increased body mass index, and an
      altered UtA Doppler. The group with intermediate-onset PET was the only one
      associated with higher 2-hour OGTT levels compared to controls. Combined models
      were developed via logistic regression analysis using maternal characteristics,
      UtA Doppler, and OGTT to predict PET. These combined models were able to detect
      around 74, 42, and 21% of women who later developed early-, intermediate-, or
      late-onset PET, respectively, with only a 5% false-positive rate. CONCLUSIONS:
      This study shows that the combination of maternal characteristics, second
      trimester UtA Doppler, and OGTT is a predictor of the development of PET in
      healthy pregnant women.

PMID- 24903218
TI  - Bacillus thuringiensis HD-1 Cry- : development of a safe, non-insecticidal
      simulant for Bacillus anthracis.
AB  - AIMS: A representative simulant for spores of Bacillus anthracis is needed for
      field testing. Bacillus thuringiensis is gaining recognition as a suitable
      organism. A strain that does not form the insecticidal, parasporal crystals that
      are characteristic of this species is a more accurate physical representative of
      B. anthracis spores. We developed noninsecticidal derivatives of two isolates of
      B. thuringiensis HD-1. METHODS AND RESULTS: Two plasmid-cured derivatives of B.
      thuringiensis HD-1, unable to make crystal toxins ('Cry(-) '), were isolated.
      These isolates and the existing Cry(-) strain, B. thuringiensis Al Hakam, were
      probed with PCR assays against the known insecticidal genes cry, vip and cyt.
      Their genomic DNA was sequenced to demonstrate a lack of insecticidal genes. This
      was confirmed by bioassays against a number of invertebrate species. Real-time
      PCR assays were developed to identify the B. thuringiensis HD-1 Cry(-)
      derivatives and an effective differential and selective medium was assessed.
      CONCLUSIONS: All three Cry(-) isolates are devoid of known insecticidal
      determinants. The B. thuringiensis HD-1 Cry(-) derivatives can easily be
      recovered from soil and identified by PCR with some selectivity. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The B. thuringiensis HD-1 Cry(-) derivatives represent
      accurate, nongenetically manipulated simulants for B. anthracis with excellent
      human and environmental safety records.

PMID- 24903220
TI  - Generalized stacking fault energies of alloys.
AB  - The generalized stacking fault energy (gamma surface) provides fundamental
      physics for understanding the plastic deformation mechanisms. Using the ab initio
      exact muffin-tin orbitals method in combination with the coherent potential
      approximation, we calculate the gamma surface for the disordered Cu-Al, Cu-Zn, Cu
      Ga, Cu-Ni, Pd-Ag and Pd-Au alloys. Studying the effect of segregation of the
      solute to the stacking fault planes shows that only the local chemical
      composition affects the gamma surface. The calculated alloying trends are
      discussed using the electronic band structure of the base and distorted
      alloys.Based on our gamma surface results, we demonstrate that the previous
      revealed 'universal scaling law' between the intrinsic energy barriers (IEBs) is
      well obeyed in random solid solutions. This greatly simplifies the calculations
      of the twinning measure parameters or the critical twinning stress. Adopting two
      twinnability measure parameters derived from the IEBs, we find that in binary Cu
      alloys, Al, Zn and Ga increase the twinnability, while Ni decreases it. Aluminum
      and gallium yield similar effects on the twinnability. 

PMID- 24903219
TI  - Hypolipidemic activity of Taraxacum mongolicum associated with the activation of
      AMP-activated protein kinase in human HepG2 cells.
AB  - This study investigated the hypolipidemic effect and potential mechanisms of T.
      mongolicum extracts. T. mongolicum was extracted by refluxing three times with
      water (TM-1), 50% ethanol (TM-2) and 95% ethanol (TM-3). TM-2 contained
      components with the most effective hypolipidemic potentials in HepG2 cells.
      Extended administration of TM-2 stimulated a significant reduction in body weight
      and levels of serum triglyceride LDL-C and total cholesterol in rats. To evaluate
      the bioactive compounds, we successively fractionated TM-2 with n-hexane (TM-4),
      dichloromethane (TM-5), ethyl acetate (TM-6), and water (TM-7). TM-4 fraction had
      the most effective hypolipidemic potential in HepG2 cells, and it decreased the
      expression of fatty acid synthase (FASN) and inhibited the activity of acetyl
      coenzyme A carboxylase (ACC) through the phosphorylation of AMP-activated protein
      kinase (AMPK). Linoleic acid, phytol and tetracosanol are bioactive compounds
      identified from TM-4. These results suggest that T. mongolicum is expected to be
      useful for hypolipidemic effects. 

PMID- 24903221
TI  - Mercuration of thiacalix[4]arenes in the cone and 1,3-alternate conformations.
AB  - The first mercuration in the thiacalixarene series using thiacalix[4]arenes
      immobilized in the cone or 1,3-alternate conformations gave a mixture of two
      monomercurated regioisomers (meta and para) in approx. 4 : 1 and 2 : 1 ratios,
      respectively. The organomercurial intermediates show unusual solid-state
      behaviour, as evidenced by the formation of eta(6) complexes, and can be easily
      transformed into halogen-substituted derivatives, so far inaccessible in
      thiacalixarene chemistry. This paves the way towards the synthesis of inherently
      chiral thiacalixarene-based receptors with an unusual substitution pattern. 

PMID- 24903222
TI  - Review of statistical methodologies for the detection of parent-of-origin effects
      in family trio genome-wide association data with binary disease traits.
AB  - The detection of parent-of-origin effects aims to identify whether the
      functionality of alleles, and in turn associated phenotypic traits, depends on
      the parental origin of the alleles. Different parent-of-origin effects have been
      identified through a variety of mechanisms and a number of statistical
      methodologies for their detection have been proposed, in particular for genome
      wide association studies (GWAS). GWAS have had limited success in explaining the
      heritability of many complex disorders and traits, but successful identification
      of parent-of-origin effects using trio (mother, father and offspring) GWAS may
      help shed light on this missing heritability. However, it is important to choose
      the most appropriate parent-of-origin test or methodology, given knowledge of the
      phenotype, amount of available data and the type of parent-of-origin effect(s)
      being considered. This review brings together the parent-of-origin detection
      methodologies available, comparing them in terms of power and type I error for a
      number of different simulated data scenarios, and finally offering guidance as to
      the most appropriate choice for the different scenarios. 

PMID- 24903223
TI  - Enhancement of adsorption selectivity for MOFs under mild activation and
      regeneration conditions.
AB  - A new concept has been proposed and proven through model experiments for
      enhancing the adsorption selectivity of metal-organic frameworks (MOFs) and
      reducing the energy cost during the activation and regeneration processes. 

PMID- 24903224
TI  - Mortality outcome among medically underserved women screened through a publicly
      funded breast cancer control program, 1997-2007.
AB  - PURPOSE: The purpose of this study was to assess treatment and mortality
      differences between women diagnosed with breast cancer through Nebraska's Every
      Woman Matters (EWM) program and women diagnosed through other sources. METHODS: A
      retrospective analysis was performed using 10 years of Nebraska Cancer Registry
      and EWM program data on women aged 40-74 years. This study used chi-square and
      multivariate logistic regression with mortality as the outcome of interest.
      RESULTS: From 1997 to 2007, 4,739 women were diagnosed with breast cancer, 435
      (9.1 %) of whom were diagnosed through EWM. The EWM and non-EWM groups differed
      significantly in age, race, marital status, location of residence at the time of
      diagnosis, neighborhood poverty level at the time of diagnosis, tumor stage at
      diagnosis, and chemotherapy. No significant differences were found between the
      two groups in radiation therapy, surgical resection, and hormone therapy. In both
      1- and 5-year multivariate mortality models, the odds of dying for those in the
      EWM program were not statistically significantly different from the odds of dying
      for those not in the EWM program. In the 1-year mortality model, residents of
      urban metropolitan counties (OR 2.079; 95 % CI 1.663-2.598) had an increased odds
      of dying compared to residents of rural counties. In the 5-year mortality model,
      black women (OR 2.239; 95 % CI 1.453-3.450), residents of areas with a high (more
      than 20 %) neighborhood poverty level at the time of diagnosis (OR 1.589; 95 % CI
      1.204-2.097), and unmarried women (OR 1.334; 95 % CI 1.164-1.528) had higher odds
      of death. Both groups have received similar treatments. CONCLUSIONS: Targeted
      outreach to vulnerable groups for cancer screening may improve cancer outcomes
      and reduce disparities.

PMID- 24903225
TI  - Obatoclax analog SC-2001 inhibits STAT3 phosphorylation through enhancing SHP-1
      expression and induces apoptosis in human breast cancer cells.
AB  - Interfering oncogenic STAT3 signaling is a promising anti-cancer strategy. We
      examined the efficacy and drug mechanism of an obatoclax analog SC-2001, a novel
      STAT3 inhibitor, in human breast cancer cells. Human breast cancer cell lines
      were used for in vitro studies. Apoptosis was examined by both flow cytometry and
      western blot. Signaling pathways were assessed by western blot. In vivo efficacy
      of SC-2001 was tested in xenograft nude mice. SC-2001 inhibited cell growth and
      induced apoptosis in association with downregulation of p-STAT3 (Tyr 705) in
      breast cancer cells. STAT3-regulated proteins, including Mcl-1, survivin, and
      cyclin D1, were repressed by SC-2001. Over-expression of STAT3 in MDA-MB-468
      cells protected cells from SC-2001-induced apoptosis. Moreover, SC-2001 enhanced
      the expression of protein tyrosine phosphatase SHP-1, a negative regulator of
      STAT3. Furthermore, the enhanced SHP-1 expression, in conjunction with increased
      SHP-1 phosphatase activity, was mediated by upregulated transcription by RFX-1.
      Chromatin immunoprecipitation assay revealed that SC-2001 increased the binding
      capacity of RFX-1 to the SHP-1 promoter. Knockdown of either RFX-1 or SHP-1
      reduced SC-2001-induced apoptosis, whereas ectopic expression of RFX-1 increased
      SHP-1 expression and enhanced the apoptotic effect of SC-2001. Importantly, SC
      2001 suppressed tumor growth in association with enhanced RFX-1 and SHP-1
      expression and p-STAT3 downregulation in MDA-MB-468 xenograft tumors. SC-2001
      induced apoptosis in breast cancer cells, an effect that was mediated by RFX-1
      upregulated SHP-1 expression and SHP-1-dependent STAT3 inactivation. Our study
      indicates targeting STAT3 signaling pathway may be a useful approach for the
      development of targeted agents for anti-breast cancer. 

PMID- 24903226
TI  - A phase I-II study of the histone deacetylase inhibitor vorinostat plus
      sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced
      breast cancer.
AB  - Histone deacetylases (HDACs) are a family of enzymes that regulate chromatin
      remodeling and gene transcription. Vorinostat is a panHDAC inhibitor that
      sensitizes breast cancer cells to taxanes and trastuzumab by suppressing HDAC6
      and Hsp90 client proteins. Fifty-five patients with clinical stage IIA-IIIC
      breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) plus vorinostat
      (200-300 mg PO BID) on days 1-3 of each paclitaxel dose plus trastuzumab (for
      Her2/neu positive disease only), followed by doxorubicin/cyclophosphamide (60/600
      mg/m(2) every 2 weeks plus pegfilgrastim). The primary study endpoint was
      pathologic complete response (pCR). pCR occurred in 13 of 24 evaluable patients
      with Her2-positive disease (54, 95 % confidence intervals [CI] 35-72 %), which
      met the prespecified study endpoint. pCR occurred in 4 of 15 patients with triple
      negative disease (27, 95 % CI 11-52 %) and none of 12 patients with ER-positive,
      Her2/neu negative disease (0, 95 % CI 0-24 %), which did not meet the
      prespecified endpoint. ER-positive tumors exhibited lower Ki67 and higher Hsp70
      expression, and HDAC6, Hsp70, p21, and p27 expression were not predictive of
      response. Vorinostat increased acetylation of Hsp90 and alpha tubulin, and
      reduced expression of Hsp90 client proteins and HDAC6 in the primary tumor.
      Combination of vorinostat with weekly paclitaxel plus trastuzumab followed by
      doxorubicin-cyclophosphamide is associated with a high pCR rate in locally
      advanced Her2/neu positive breast cancer. Consistent with cell line and xenograft
      data, vorinostat increased acetylation of Hsp90 and alpha tubulin, and decreased
      Hsp90 client protein and HDAC6 expression in human breast cancers in vivo. 

PMID- 24903227
TI  - CD36, a scavenger receptor implicated in atherosclerosis.
AB  - CD36 is a membrane glycoprotein that is present on various types of cells,
      including monocytes, macrophages, microvascular endothelial cells, adipocytes and
      platelets. Macrophage CD36 participates in atherosclerotic arterial lesion
      formation through its interaction with oxidized low-density lipoprotein (oxLDL),
      which triggers signaling cascades for inflammatory responses. CD36 functions in
      oxLDL uptake and foam cell formation, which is the initial critical stage of
      atherosclerosis. In addition, oxLDL via CD36 inhibits macrophage migration, which
      may be a macrophage-trapping mechanism in atherosclerotic lesions. The role of
      CD36 was examined in in vitro studies and in vivo experiments, which investigated
      various functions of CD36 in atherosclerosis and revealed that CD36 deficiency
      reduces atherosclerotic lesion formation. Platelet CD36 also promotes
      atherosclerotic inflammatory processes and is involved in thrombus formation
      after atherosclerotic plaque rupture. Because CD36 is an essential component of
      atherosclerosis, defining the function of CD36 and its corresponding signaling
      pathway may lead to a new treatment strategy for atherosclerosis. 

PMID- 24903228
TI  - Can magnetic resonance spectroscopy differentiate endometrial cancer?
AB  - OBJECTIVES: To investigate whether the choline-containing compounds (Cho)
      obtained from three-dimensional (1)H magnetic resonance (MR) spectroscopy can
      differentiate endometrial cancer (ECa) from benign lesions in endometria or in
      submucosa (BLs-ESm) and is associated with the aggressiveness of ECa. METHODS:
      Fifty-seven patients (ECa, 38; BLs-ESm, 19) underwent preoperative multi-voxel MR
      spectroscopy at 3.0 T. The ratio of the sum of the Cho peak integral to the sum
      of the unsuppressed water peak integral (Cho/water) and the coefficient of
      variation (CV) used to describe the variability of Cho/water in one lesion were
      calculated. RESULTS: Mean Cho/water (+/-standard deviation [SD]) was (3.02 +/-
      1.43) * 10(-3) for ECa and (1.68 +/- 0.33) * 10(-3) for BLs-ESm (p < 0.001). Mean
      Cho/water was (4.42 +/- 1.53) * 10(-3) for type II ECa and (2.65 +/- 1.17) * 10(
      3) for type I ECa (p = 0.001). There were no significant differences among
      different stages of ECa (p = 0.107) or different grades of ECa (p = 0.142). The
      Cho/water was positively correlated with tumour stage (r = 0.386, p = 0.017) and
      size (r = 0.333, p = 0.041). The CV was also positively correlated with tumour
      stage (r = 0.537, p = 0.001) and size (r = 0.34, p = 0.037). CONCLUSION: The
      Cho/water can differentiate ECa from BLs-ESm and differentiate type II from type
      I ECa, but cannot differentiate different stages of ECa or different grades of
      ECa. Cho/water increased with the increase of tumour stage and size. KEY POINTS:
      * First report to attempt to assess ECa aggressiveness with magnetic resonance
      spectroscopy (MRS). * MRS can differentiate type I from type II ECa. * MRS can
      differentiate ECa from BLs-ESm. * MRS cannot differentiate different stages of
      ECa or different grades of ECa. * Cho/water increased with the increase of tumour
      stage and size.

PMID- 24903229
TI  - Spectral CT evaluation of interstitial brachytherapy in pancreatic carcinoma
      xenografts: preliminary animal experience.
AB  - OBJECTIVES: We sought to evaluate the capability of spectral CT to detect the
      therapeutic response to (125)I interstitial brachytherapy in a pancreatic
      carcinoma xenograft nude mouse model. METHODS: Twenty mice bearing SWl990 human
      pancreatic cancer cell xenografts were randomly separated into two groups:
      experimental (n = 10; 1.0 mCi) and control (n = 10; 0 mCi). After a two-week
      treatment, spectral CT was performed. Contrast-to-noise ratio (CNR) and iodine
      concentration (IC) in the lesions were measured and normalized to the muscle
      tissue, and nIC CD31 immunohistochemistry was used to measure microvessel density
      (MVD). The relationships between the nIC and MVD of the tumours were analysed.
      RESULTS: The nIC of the experimental group was significantly lower than that of
      the control group during the multiphase examination. A significant difference in
      the MVD was observed between the two groups (P <0.001). The nIC values of the
      three-phase scans have a certain positive correlation with MVD (r = 0.57, p <
      0.0001; r = 0.48, p = 0.002; r = 0.63, p = 0.0017 in the 10, 25, and 60 s phase,
      respectively). CONCLUSIONS: Spectral CT can be a useful non-invasive imaging
      modality in evaluating the therapeutic effect of (125)I interstitial
      brachytherapy to a pancreatic carcinoma. KEY POINTS: Spectral CT offers
      opportunities to assess therapeutic response in pancreatic cancer cases. Spectral
      CT findings correlated with vascular changes associated with (125)I seed
      implantation. Spectral CT with monochromatic imaging removed most (125)I seed
      artefacts.

PMID- 24903230
TI  - Effect of inspiration on airway dimensions measured in maximal inspiration CT
      images of subjects without airflow limitation.
AB  - OBJECTIVES: To study the effect of inspiration on airway dimensions measured in
      voluntary inspiration breath-hold examinations. METHODS: 961 subjects with normal
      spirometry were selected from the Danish Lung Cancer Screening Trial. Subjects
      were examined annually for five years with low-dose CT. Automated software was
      utilized to segment lungs and airways, identify segmental bronchi, and match
      airway branches in all images of the same subject. Inspiration level was defined
      as segmented total lung volume (TLV) divided by predicted total lung capacity
      (pTLC). Mixed-effects models were used to predict relative change in lumen
      diameter (ALD) and wall thickness (AWT) in airways of generation 0 (trachea) to 7
      and segmental bronchi (R1-R10 and L1-L10) from relative changes in inspiration
      level. RESULTS: Relative changes in ALD were related to relative changes in
      TLV/pTLC, and this distensibility increased with generation (p < 0.001). Relative
      changes in AWT were inversely related to relative changes in TLV/pTLC in
      generation 3--7 (p < 0.001). Segmental bronchi were widely dispersed in terms of
      ALD (5.7 +/- 0.7 mm), AWT (0.86 +/- 0.07 mm), and distensibility (23.5 +/- 7.7%).
      CONCLUSIONS: Subjects who inspire more deeply prior to imaging have larger ALD
      and smaller AWT. This effect is more pronounced in higher-generation airways.
      Therefore, adjustment of inspiration level is necessary to accurately assess
      airway dimensions. KEY POINTS: Airway lumen diameter increases and wall thickness
      decreases with inspiration. The effect of inspiration is greater in higher
      generation (more peripheral) airways. Airways of generation 5 and beyond are as
      distensible as lung parenchyma. Airway dimensions measured from CT should be
      adjusted for inspiration level.

PMID- 24903231
TI  - Primary sequence contribution to the optical function of the eye lens.
AB  - The crystallins have relatively high refractive increments compared to other
      proteins. The Greek key motif in betagamma-crystallins was compared with that in
      other proteins, using predictive analysis from a protein database, to see whether
      this may be related to the refractive increment. Crystallins with Greek keys
      motifs have significantly higher refractive increments and more salt bridges than
      other proteins with Greek key domains. Specific amino acid substitutions: lysine
      and glutamic acid residues are replaced by arginine and aspartic acid,
      respectively as refractive increment increases. These trends are also seen in S
      crystallins suggesting that the primary sequence of crystallins may be
      specifically enriched with amino acids with appropriate values of refractive
      increment to meet optical requirements. Comparison of crystallins from five
      species: two aquatic and three terrestrial shows that the lysine/arginine
      correlation with refractive increment occurs in all species investigated. This
      may be linked with formation and maintenance of salt bridges. 

PMID- 24903232
TI  - Effect of intermittent and daily regimens of minodronic Acid on bone metabolism
      in an ovariectomized rat model of osteoporosis.
AB  - The goal of the study was to compare the effects of minodronic acid on bone
      mineral density (BMD) and bone turnover in a rat ovariectomized (OVX)
      osteoporosis model, using two intermittent treatment regimens (weekly and 4
      continuous days every 4 weeks) and a daily regimen. Female F344 rats (age 14
      weeks) underwent ovariectomy or a sham operation. Minodronic acid was orally
      administered at 0.042, 0.21, and 1.05 mg/kg in the intermittent regimens, and at
      0.03 and 0.15 mg/kg in the daily regimen for 12 weeks from the day after surgery.
      Minodronic acid dose-dependently ameliorated the decreases in areal BMD of the
      lumbar vertebrae and femur, and volumetric BMD of total and trabecular bone in
      the distal femur. Minodronic acid also suppressed the increase in urinary
      deoxypyridinoline levels and reduced serum osteocalcin levels. In bone
      histomorphometry, all three minodronic acid regimens suppressed OVX-induced
      increases in bone turnover at the tissue level and ameliorated all structural
      indices, except that an effect on trabecular thickness only occurred with daily
      treatment. In conclusion, minodronic acid administered weekly or for 4 continuous
      days every 4 weeks suppressed increased bone resorption and BMD to a similar
      extent to that of a similar total dose given daily in a rat OVX model. 

PMID- 24903234
TI  - Infliximab infusion resulting in rapid resolution of episcleritis.

PMID- 24903233
TI  - Genetics, ancestry, and hypertension: implications for targeted antihypertensive
      therapies.
AB  - Hypertension is the most common chronic condition seen by physicians in
      ambulatory care and a condition for which life-long medications are commonly
      prescribed. There is evidence for genetic factors influencing blood pressure
      variation in populations and response to medications. This review summarizes
      recent genetic discoveries that surround blood pressure, hypertension, and
      antihypertensive drug response from genome-wide association studies, while
      highlighting ancestry-specific findings and any potential implication for drug
      therapy targets. Genome-wide association studies have identified several novel
      loci for inter-individual variation of blood pressure and hypertension risk in
      the general population. Evidence from pharmacogenetic studies suggests that genes
      influence the blood pressure response to antihypertensive drugs, although results
      are somewhat inconsistent across studies. There is still much work that remains
      to be done to identify genes both for efficacy and adverse events of
      antihypertensive medications. 

PMID- 24903235
TI  - Small soft tissue sarcomas do metastasize: identification of high-risk tumors.
AB  - BACKGROUND: Small (<= 5 cm) soft tissue sarcomas (STS) of the extremities and the
      trunk wall generally have a favorable prognosis. However, 1 of 10 patients do
      develop metastases, and we therefore aimed to determine predictors of metastasis
      in a population-based cohort of patients with small STSs. PATIENTS AND METHODS:
      In the southern Sweden health care region, 848 adult patients with STS of the
      extremities or the trunk wall were diagnosed between 1986 and 2010. Of these, 243
      STS (29 %) were <=5 cm. Prognostic evaluation was performed in 229 patients with
      localized disease at diagnosis, 181 of whom had histologic high-grade tumors.
      RESULTS: None of the 48 patients with low-grade tumors developed metastases,
      whereas 24 of 181 patients with high-grade tumors (13 %) tumors did. Presence of
      either tumor necrosis or vascular invasion predicted development of metastases
      with a hazard ratio of 2.9 (95 % CI, 1.0-7.9), and tumors with both factors had a
      hazard ratio of 12 (95 % CI, 4.1-37) for metastasis (adjusted for size).
      CONCLUSIONS: Our population-based series of STSs <=5 cm demonstrate an overall
      good prognosis with metastases developing in 13 % of the patients with high-grade
      tumors. Tumor necrosis and vascular invasion were the major predictors of
      metastatic disease in this subset. Tumors with both these risk factors
      metastasized in 8 of 18 patients, which corresponds to a 12-fold increased risk
      of metastasis. These findings suggest that although small STS generally are
      linked to a good prognosis, necrosis and vascular invasion are features
      indicating biologically aggressive tumors for which treatment and surveillance
      should equal that for larger tumors.

PMID- 24903236
TI  - Survival advantage of radiofrequency ablation over transarterial
      chemoembolization for patients with hepatocellular carcinoma and good performance
      status within the Milan criteria.
AB  - BACKGROUND: Performance status is closely linked with survival in patients with
      hepatocellular carcinoma (HCC). We evaluated the impact of performance status on
      patients with small HCC receiving radiofrequency ablation (RFA) versus
      transarterial chemoembolization (TACE). METHODS: A total of 424 and 282 patients
      within the Milan criteria undergoing RFA and TACE, respectively, were analyzed.
      Patients were classified as performance status 0 (n = 516) and performance status
      >=1 (n = 190) groups. A propensity-score matching analysis with preset caliper
      width was used. A total of 167 and 68 matched pairs were selected from patients
      with a performance status of 0 and >=1, respectively. RESULTS: Radiofrequency
      ablation provided significantly better long-term survival than TACE for patients
      within the Milan criteria (p < 0.01). After being stratified by performance
      status and matched in the propensity model, the baseline characteristics were
      similar between the RFA and TACE groups for patients with a performance status of
      0 or >=1. RFA provided significantly better long-term survival than TACE in
      patients with a performance status of 0 in the propensity model (p < 0.05); TACE
      was significantly associated with 1.784-fold increased risk of mortality (95 %
      confidence interval 1.075-2.506) by using the Cox proportional hazards model.
      TACE was not a significant prognostic predictor in patients with a performance
      status >=1 in the propensity model. CONCLUSIONS: For HCC patients within the
      Milan criteria with a performance status of 0, RFA provides better long-term
      survival than TACE. RFA should be considered a priority treatment in inoperable
      HCC patients within the Milan criteria. Performance status is a feasible
      surrogate marker to enhance treatment allocation.

PMID- 24903237
TI  - EPR investigation of UV light effect on calcium carbonate powders with different
      grain sizes.
AB  - This study is based on investigation of calcium carbonate powders with different
      grain sizes exposed to UV light. Calcium carbonate is widely used in many
      branches of industry, e.g. as a filler for polymer materials; therefore, knowing
      its properties, among them also its reaction to UV light, is essential. Samples
      of powdered calcium carbonate with average grain sizes of 69 and 300 nm and 2.1,
      6, 16, 25 um were used in this investigation. Measurements were performed at room
      temperature using EPR X-band spectrometer, and they have shown the additional
      signals induced by the light from Hg lamp. The effect of annealing of the micro
      grain samples was also studied. The spectra of four micro-grain samples after
      irradiation are similar, but there are differences between them and the other two
      powders, which could be related to the different sizes of their grains. Further
      studies based on these preliminary results may prove useful in research of
      photodegradation of CaCO3-filled materials, as well as helpful in increasing the
      accuracy of dating of archaeological and geological objects. 

PMID- 24903238
TI  - Prevalence of tobacco use and exposure to environmental tobacco smoke among saudi
      medical students in Riyadh, Saudi Arabia.
AB  - This study was designed to determine the prevalence of active smoking and
      environmental tobacco smoke (ETS) exposure among medical students in Riyadh,
      Saudi Arabia, and to examine their attitudes and beliefs towards tobacco control
      programs. The investigation was a cross-sectional study conducted during the
      first semester of 2013 at King Saud University School of Medicine located in
      Riyadh, Saudi Arabia. Invited to participate in this study were 1,789 medical
      students. A descriptive data analysis was performed. A total of 805 medical
      students completed the questionnaire. The prevalence of experimentation with
      cigarette smoking was 11.3%. The estimated prevalence of current smoking among
      the study participants was 4.7%. The majority of the students held positive
      attitudes toward tobacco control and approximately 93.1% of the students felt
      that health care professionals should be required to receive training for
      cessation counseling while only 36.8% of the students reported having received
      any training in this area. Over the study's duration 57.7% of participants
      reported that ETS exposure was much higher in public places, while 13.9% reported
      exposure at home. This investigation revealed that ETS exposure among medical
      students in Riyadh is at an alarmingly high rate. The data suggests a need for a
      more robust smoke-free policy and a commitment to greater enforcement in public
      places. The results of the study also demonstrate a positive attitude among
      participants for tobacco control. It also indicates a need for cessation
      counseling and training which could be incorporated into medical school
      curriculum.

PMID- 24903239
TI  - Influence of annexin A7 on insulin sensitivity of cellular glucose uptake.
AB  - Insulin sensitivity is decreased by prostaglandin E2 (PGE2), a major product of
      cyclooxygenase (COX). As shown in erythrocytes, PGE2 formation is inhibited by
      annexin A7. The present study defined the role of annexin A7 in glucose
      metabolism. Gene-targeted mice lacking annexin A7 (annexin7 (-/-)) were compared
      to wild-type mice (annexin7 (+/+)). The serum 6-Keto-prostaglandin-F1alpha (6
      Keto-PGF1alpha) concentration was measured by ELISA and hepatic COX activity
      determined by an enzyme assay. Expression of COX-1, COX-2, prostaglandin E
      synthase, GLUT-4, and insulin receptor was determined by Western blotting.
      Glucose and insulin serum concentrations were analyzed following an
      intraperitoneal glucose load and glucose serum levels after intraperitoneal
      injection of insulin. Experiments were done without and with pretreatment of the
      mice with COX-inhibitor aspirin. The serum 6-Keto-PGF1alpha level and hepatic COX
      activity were significantly higher in annexin7 (-/-) than in annexin7 (+/+) mice.
      Hepatic COX-1 expression was higher in annexin7 (-/-) mice. Glucose tolerance was
      decreased in annexin7 (-/-) mice. Intraperitoneal insulin injection decreased the
      serum glucose level in both genotypes, an effect significantly less pronounced in
      annexin7 (-/-) mice. Glucose-induced insulin secretion was higher in annexin7 (-/
      ) mice. GLUT-4 expression in skeletal muscle from annexin7 (-/-) mice was
      reduced. Aspirin pretreatment lowered the increase in insulin concentration
      following glucose injection in both genotypes and virtually abrogated the
      differences in serum insulin between the genotypes. Aspirin pretreatment improved
      glucose tolerance in annexin7 (-/-) mice. In conclusion, annexin A7 influences
      insulin sensitivity of cellular glucose uptake and thus glucose tolerance. These
      effects depend on COX activity. 

PMID- 24903240
TI  - Preserved regulation of renal perfusion pressure by small and intermediate
      conductance KCa channels in hypertensive mice with or without renal failure.
AB  - The purpose of this study was to assess, in the murine kidney, the mechanisms
      underlying the endothelium-dependent control of vascular tone and whether or not,
      in a severe model of hypertension and renal failure, KCa channels contribute to
      its regulation. Wild-type (BL) and double-transgenic female mice expressing human
      angiotensinogen and renin (AR) genes received either control or a high-salt diet
      associated to a nitric oxide (NO) synthase inhibitor treatment (BLSL and ARSL).
      Changes in renal perfusion pressure (RPP) were measured in isolated perfused
      kidneys. BLSL and AR were moderately hypertensive without kidney disease while
      ARSL developed severe hypertension and renal failure. In the four groups,
      methacholine induced biphasic endothelium-dependent responses, a transient
      decrease in RPP followed by a cyclooxygenase-dependent increase in RPP. In the
      presence or not of indomethacin, the vasodilatations were poorly sensitive to NO
      synthase inhibition. However, in the presence of cyclooxygenase and NO synthase
      inhibitors, apamin, and/or TRAM-34, blockers of KCa2.3 and KCa3.1, respectively,
      abolished the decrease in RPP in response to either methacholine or the two
      activators of KCa2.3/KCa3.1, NS309, and SKA-31. Thus, KCa2/3 channels play a
      major role in the regulation of murine kidney perfusion and this mechanism is
      maintained in hypertension, even when severe and associated with kidney damage. 

PMID- 24903241
TI  - Activity-dependent changes in excitability of perirhinal cortex networks in
      vitro.
AB  - Rat brain slices comprising the perirhinal cortex (PC) and a portion of the
      lateral nucleus of the amygdala (LA), in standard medium, can generate
      synchronous oscillatory activity that is associated with action potential
      discharge and reflects the activation of glutamatergic and GABAergic receptors.
      We report here that similar synchronous oscillatory events are recorded in the PC
      in response to single-shock, electrical stimuli delivered in LA. In addition, we
      found that the latency of these responses progressively increased when the
      stimulus interval was varied from 10 to 1 s; for example, the response latency
      during stimuli delivered at 1 Hz was more than twofold longer than that seen
      during stimulation at 0.1 Hz. This prolongation in latency occurred after
      approximately 5 stimuli, attained a steady value after 24-35 stimuli, and
      recovered to control values 30 s after stimulation arrest. These frequency
      dependent changes in latency continued to occur during NMDA receptor antagonism
      but weakened following application of GABAA and/or GABAB receptor blockers. Our
      findings identify a new type of short-term plasticity that is mediated by GABA
      receptor function and may play a role in decreasing neuronal network
      synchronization during repeated activation. We propose that this frequency
      dependent adaptive mechanism influences the excitability of limbic networks, thus
      potentially controlling epileptiform synchronization.

PMID- 24903242
TI  - Comment on Suzuki et al.: "Fluctuation of serum C3 levels reflects disease
      activity and metabolic background in patients with IgA nephropathy".

PMID- 24903243
TI  - Fluctuation of serum C3 levels reflects disease activity and metabolic background
      in patients with IgA nephropathy: response to comment.

PMID- 24903244
TI  - The usefulness of gated blood pool scintigraphy for right ventricular function
      evaluation in pulmonary embolism patients.
AB  - OBJECTIVE: According to the international registry ICOPER, right ventricular (RV)
      dysfunction is the most significant predictor of mortality in patients with
      pulmonary embolism (PE). AIM: To identify the most informative indicators of
      gated blood pool single photon emission computer tomography (GBP-SPECT) for
      evaluation of RV function in patients with PE. METHODS: A total of 52 patients
      were included in the study. The main group (n = 37) comprised patients with PE,
      and the comparison group (n = 15) patients suffering from coronary heart disease
      (NYHA class I-II). All patients received GBP-SPECT, and assessment of plasma
      levels of endothelin-1, stable nitric oxide (NO) metabolites, and 6-keto-PG
      F1alpha. RESULTS: In patients with PE, RV end-systolic volume, stroke volume,
      ejection fraction, peak ejection rate, peak filling rate, and mean filling rate
      were significantly lower in comparison with patients without PE. In patients with
      PE, the levels of endothelin-1, 6-keto-PG F1alpha, and stable NO metabolites were
      increased in comparison with patients without PE. CONCLUSIONS: GBP-SPECT
      facilitates verification of RV dysfunction in patients without massive PE or
      severe pulmonary hypertension. Dissociation between the volume of PE and degree
      of RV dysfunction may be caused by an unbalance between humoral vasoactive
      factors.

PMID- 24903245
TI  - Contrast between hypervascularized liver lesions and hepatic parenchyma: early
      dynamic PET versus contrast-enhanced CT.
AB  - OBJECTIVES: To detect hypervascularized liver lesions, early dynamic (ED) (18)F
      FDG PET may be an alternative when contrast-enhanced (CE) imaging is infeasible.
      This retrospective pilot analysis compared contrast between such lesions and
      liver parenchyma, an important objective image quality variable, in ED PET versus
      CE CT. MATERIALS AND METHODS: Twenty-eight hypervascularized liver lesions
      detected by CE CT [21 (75%) hepatocellular carcinomas; mean (range) diameter 4.9
      +/- 3.5 (1-14) cm] in 20 patients were scanned with ED PET. Using regions of
      interest, maximum and mean lesional and parenchymal signals at baseline, arterial
      and venous phases were calculated for ED PET and CE CT. RESULTS:
      Lesional/parenchymal signal ratio was significantly higher (P < 0.005) with ED
      PET versus CE CT at the arterial phase and similar between the methods at the
      venous phase. CONCLUSION: In liver imaging, ED PET generates greater lesional
      parenchymal contrast during the arterial phase than does CE CT; these
      observations should be formally, prospectively evaluated.

PMID- 24903247
TI  - Possibilities for the efficient utilisation of spent geothermal waters.
AB  - Waters located at greater depths usually exhibit high mineral content, which
      necessitates the use of closed systems, i.e. re-injecting them into the formation
      after recovering the heat. This significantly reduces investment efficiency owing
      to the need to drill absorption wells and to perform anti-corrosion and anti
      clogging procedures. In this paper, possibilities for the efficient utilisation
      of cooled geothermal waters are considered, particularly with respect to open or
      mixed geothermal water installations. Where cooled water desalination
      technologies are used, this allows the water to be demineralised and used to meet
      local needs (as drinking water and for leisure purposes). The retentate left as a
      by-product of the process contains valuable ingredients that can be used for
      balneological and/or leisure purposes. Thus, the technology for desalinating
      spent geothermal waters with high mineral content allows improved water
      management on a local scale and makes it possible to minimise the environmental
      threat resulting from the need to dump these waters into waterways or surface
      water bodies and/or inject them into the formation. The paper is concerned with
      Polish geothermal system and provides information about the parameters of Polish
      geothermal waters. 

PMID- 24903248
TI  - Seasonal trends, meteorological impacts, and associated health risks with
      atmospheric concentrations of gaseous pollutants at an Indian coastal city.
AB  - This study presents surface ozone (O3) and carbon monoxide (CO) measurements
      conducted at Bhubaneswar from December 2010 to November 2012 and attempts for the
      very first time a health risk assessment of the atmospheric trace gases. Seasonal
      variation in average 24 h O3 and CO shows a distinct winter (December to
      February) maxima of 38.98 +/- 9.32 and 604.51 +/- 145.91 ppbv, respectively. O3
      and CO characteristics and their distribution were studied in the form of
      seasonal/diurnal variations, air flow patterns, inversion conditions, and
      meteorological parameters. The observed winter high is likely due to higher
      regional emissions, the presence of a shallower boundary layer, and long-range
      transport of pollutants from the Indo-Gangetic Plain (IGP). Large differences
      between daytime and nighttime O3 values during winter compared to other seasons
      suggest that photochemistry is much more active on this site during winter. O3
      and CO observations are classified in continental and marine air masses, and
      continental influence is estimated to increase O3 and CO by up to 20 and 120
      ppbv, respectively. Correlation studies between O3 and CO in various seasons
      indicated the role of CO as one of the O3 precursors. Health risk estimates
      predict 48 cases of total premature mortality in adults due to ambient
      tropospheric O3 during the study period. Comparatively low CO concentrations at
      the site do not lead to any health effects even during winter. This study
      highlights the possible health risks associated with O3 and CO pollution in
      Bhubaneswar, but these results are derived from point measurements and should be
      complemented either with regional scale observations or chemical transport models
      for use in design of mitigation policies.

PMID- 24903246
TI  - Linking adiponectin and autophagy in the regulation of breast cancer metastasis.
AB  - Adipokines within the tumor microenvironment may play important roles in
      regulating the early steps of breast cancer metastasis. Adiponectin (AdipoQ) is
      the most abundant adipokine and exists in multiple forms: full-length multimers
      (fAd) and a cleaved, globular isoform (gAd). While these isoforms are observed as
      having distinct biological properties, nearly all investigation into AdipoQ in
      breast cancer has focused on the antitumor roles of fAd, while mostly ignoring
      gAd. However, evidence from other disease settings suggests that gAd is linked to
      processes known to promote metastasis. Here, we discuss key areas in which
      knowledge about AdipoQ in breast cancer is lacking, expressly focusing on data
      suggesting that gAd is elevated in the microenvironment and may act directly on
      invasive breast cancer cells to support their initial metastatic progression. We
      discuss autophagy as a potential mechanism of action for this effect. Overall,
      given that AdipoQ and AdipoQ receptor agonists have been proposed as therapeutic
      strategies, it is necessary to better understand the various functions of these
      regulatory molecules in metastatic breast cancer. Doing so will help ensure the
      most effective approaches to treating this disease, for which there remain no
      curative options. 

PMID- 24903249
TI  - Quality assessment of digested sludges produced by advanced stabilization
      processes.
AB  - The European Union (EU) Project Routes aimed to discover new routes in sludge
      stabilization treatments leading to high-quality digested sludge, suitable for
      land application. In order to investigate the impact of different enhanced sludge
      stabilization processes such as (a) thermophilic digestion integrated with
      thermal hydrolysis pretreatment (TT), (b) sonication before
      mesophilic/thermophilic digestion (UMT), and (c) sequential anaerobic/aerobic
      digestion (AA) on digested sludge quality, a broad class of conventional and
      emerging organic micropollutants as well as ecotoxicity was analyzed, extending
      the assessment beyond the parameters typically considered (i.e., stability index
      and heavy metals). The stability index was improved by adding aerobic
      posttreatment or by operating dual-stage process but not by pretreatment
      integration. Filterability was worsened by thermophilic digestion, either alone
      (TT) or coupled with mesophilic digestion (UMT). The concentrations of heavy
      metals, present in ranking order Zn > Cu > Pb > Cr ~ Ni > Cd > Hg, were always
      below the current legal requirements for use on land and were not removed during
      the processes. Removals of conventional and emerging organic pollutants were
      greatly enhanced by performing double-stage digestion (UMT and AA treatment)
      compared to a single-stage process as TT; the same trend was found as regards
      toxicity reduction. Overall, all the digested sludges exhibited toxicity to the
      soil bacterium Arthrobacter globiformis at concentrations about factor 100 higher
      than the usual application rate of sludge to soil in Europe. For earthworms, a
      safety margin of factor 30 was generally achieved for all the digested samples. 

PMID- 24903250
TI  - Trace metal quantification in bladder biopsies from tumoral lesions of Tunisian
      cancer and controls subjects.
AB  - The incidence of bladder tumors has been dramatically increasing since the 1970s,
      possibly as a consequence of ongoing environmental pollution. Previous studies
      have provided some evidence of an association between cancer and exposure to
      carcinogenic metals. In order to examine the association between levels of toxic
      metals in patients with bladder tumors and controls, the amounts of arsenic,
      cadmium, chromium, and nickel were measured in tumoral lesions and adjacent
      normal part of the bladder mucosa excised for carcinoma and compared with those
      in the bladder mucosa of volunteer subjects operated for non-neoplastic diseases.
      The quantification of metals in tissue was assessed by atomic absorption
      spectroscopy. In tumoral tissues of the excised bladder mucosa, content of Cr and
      Ni was significantly low compared to that of adjacent normal tissues and control
      tissues while that of As and Cd in normal tissues adjacent to the tumor were
      significantly elevated compared to controls. Though the sample size was small,
      the present study shows that concentrations of metals such as Cd, Cr, As, and Ni
      in bladder tissue may be used as a biomarker of exposure. On the basis of the
      results obtained in this study, high amounts of As and Cd in adjacent normal
      parts of the bladders with carcinomas compared to controls would strongly suggest
      possible, individual or synergistic, effects of these pollutants on enzymatic
      systems, priming an oncogenic pathway. 

PMID- 24903251
TI  - Water and acrylamide monomer transfer rates from a settling basin to
      groundwaters.
AB  - The aim of this paper was to estimate the potential leakage of acrylamide
      monomer, used for flocculation in a settling basin, towards the groundwaters.
      Surface-groundwater interactions were conceptualized with a groundwater transport
      model, using a transfer rate to describe the clogged properties of the interface.
      The change in the transfer rate as a function of the spreading of the clogged
      layer in the settling basin was characterized with respect to time. It is shown
      that the water and the Acrylamide transfer rate are not controlled by the
      spreading of the clogged layer until this layer fully covers the interface. When
      the clogged layer spreads out, the transfer rate remains in the same order of
      magnitude until the area covered reaches 80 %. The main flux takes place through
      bank seepage. In these early stage conditions of a working settling basin, the
      acrylamide flux towards groundwaters remains constant, at close to 10 g/year (+/
      5).

PMID- 24903252
TI  - Bioremediation treatment of hydrocarbon-contaminated Arctic soils: influencing
      parameters.
AB  - The Arctic environment is very vulnerable and sensitive to hydrocarbon
      pollutants. Soil bioremediation is attracting interest as a promising and cost
      effective clean-up and soil decontamination technology in the Arctic regions.
      However, remoteness, lack of appropriate infrastructure, the harsh climatic
      conditions in the Arctic and some physical and chemical properties of Arctic
      soils may reduce the performance and limit the application of this technology.
      Therefore, understanding the weaknesses and bottlenecks in the treatment plans,
      identifying their associated hazards, and providing precautionary measures are
      essential to improve the overall efficiency and performance of a bioremediation
      strategy. The aim of this paper is to review the bioremediation techniques and
      strategies using microorganisms for treatment of hydrocarbon-contaminated Arctic
      soils. It takes account of Arctic operational conditions and discusses the
      factors influencing the performance of a bioremediation treatment plan.
      Preliminary hazard analysis is used as a technique to identify and assess the
      hazards that threaten the reliability and maintainability of a bioremediation
      treatment technology. Some key parameters with regard to the feasibility of the
      suggested preventive/corrective measures are described as well. 

PMID- 24903253
TI  - Concentration and health risk evaluation of heavy metals in market-sold
      vegetables and fishes based on questionnaires in Beijing, China.
AB  - Concentrations of heavy metals (As, Cd, Pb, Cu, Ni, Fe, Mn, and Zn) in market
      vegetables and fishes in Beijing, China, are investigated, and their health risk
      to local consumers is evaluated by calculating the target hazard quotient (THQ).
      The heavy metal concentrations in vegetables and fishes ranged from not
      detectable (ND) to 0.21 mg/kg fresh weight (f.w.) (As), ND to 0.10 mg/kg f.w.
      (Cd), and n.d to 0.57 mg/kg f.w. (Pb), with average concentrations of 0.17, 0.04,
      and 0.24 mg/kg f.w., respectively. The measured concentrations of As, Cd, Pb, Cu,
      Ni, Fe, Mn, and Zn are generally lower than the safety limits given by the
      Chinese regulation safety and quality standards of agriculture products (GB2762
      2012). As, Cd, and Pb contaminations are found in vegetables and fishes. The
      exceeding standard rates are 19 % for As, 3 % for Cd, and 25 % for Pb. Pb
      contaminations are found quite focused on the fish samples from traditional agri
      product markets. The paper further analyzed the health risk of heavy metals in
      vegetables and fishes respectively from supermarkets and traditional agri-product
      markets; the results showed that the fishes of traditional agri-product markets
      have higher health risk, while the supermarkets have vegetables of higher heavy
      metal risk, and the supervision should be strengthened in the fish supply
      channels in traditional agri-product markets.

PMID- 24903254
TI  - Evaluation of hydrocephalus and other cerebrospinal fluid disorders with MRI: An
      update.
AB  - MRI is not only beneficial in the diagnosis of cerebrospinal fluid (CSF)-related
      diseases, but also aids in planning the management and post-surgery follow-up of
      the patients. With recent advances in MRI systems, there are many newly developed
      sequences and techniques that rapidly enable evaluation of CSF-related disorders
      with greater accuracy. For a better assessment of this group of disorders,
      radiologists should follow the developments closely and should be able to apply
      them when necessary. In this pictorial review, the role of MRI in the evaluation
      of hydrocephalus, CSF diversion techniques, and other CSF disorders is
      illustrated. Teaching Points * The 3D-SPACE seems to be most efficient technique
      for evaluation of hydrocephalus and ventriculostomy. * In complex cases, PC-MRI,
      3D-heavily T2W, and/or CE-MRC images may prevent false results of 3D-SPACE.* MRI
      is beneficial in the diagnosis and management of hydrocephalus and other CSF
      related diseases. 

PMID- 24903255
TI  - Predictors and clinical implications of minimal ST-segment elevation in patients
      with ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: Some patients with suspected ST-segment elevation (STE) myocardial
      infarction (STEMI) show STE that does not fulfill the current criteria for STEMI.
      The purpose of this study was to investigate the characteristics and prognoses of
      patients with minimal STEMI. METHODS: Between November 2007 and December 2011,
      546 patients who underwent primary percutaneous coronary intervention (PCI) for
      STEMI were enrolled. RESULTS: The minimal STE group had a higher proportion of
      women (30.2 vs. 21.0%, p = 0.031), better pre-PCI antegrade flow (Thrombolysis in
      Myocardial Infarction flow 2-3, 30.2 vs. 18.8%, p = 0.006) and better
      collateralization (Rentrop score 2-3, 27.4 vs. 18.1%, p = 0.024) compared to the
      definite STE group. Multivariate analysis showed that each of them were
      independent predictors for minimal STE. However, 1-year mortality of the minimal
      STE group did not differ from that of the definite STE group (7.1 vs. 9.3%, log
      rank p = 0.315). CONCLUSIONS: Female gender, good collateral flow and good pre
      PCI antegrade flow were independent predictors for minimal STE in patients with
      STEMI. However, minimal STE was not related to a good prognosis in patients with
      STEMI.

PMID- 24903256
TI  - Epitope profiling via mixture modeling of ranked data.
AB  - We propose the use of probability models for ranked data as a useful alternative
      to a quantitative data analysis to investigate the outcome of bioassay
      experiments when the preliminary choice of an appropriate normalization method
      for the raw numerical responses is difficult or subject to criticism. We review
      standard distance-based and multistage ranking models and propose an original
      generalization of the Plackett-Luce model to account for the order of the ranking
      elicitation process. The usefulness of the novel model is illustrated with its
      maximum likelihood estimation for a real data set. Specifically, we address the
      heterogeneous nature of the experimental units via model-based clustering and
      detail the necessary steps for a successful likelihood maximization through a
      hybrid version of the expectation-maximization algorithm. The performance of the
      mixture model using the new distribution as mixture components is then compared
      with alternative mixture models for random rankings. A discussion on the
      interpretation of the identified clusters and a comparison with more standard
      quantitative approaches are finally provided.

PMID- 24903257
TI  - The pain, the oncologist.

PMID- 24903258
TI  - Worrying about one's children after breast cancer diagnosis: desired timing of
      psychosocial intervention.
AB  - BACKGROUND: The purposes of this observational study were to analyze at what time
      point mothers desired psychosocial support regarding the worry about their
      children during the year after breast cancer diagnosis and to identify any
      psychosocial factors associated with this worry. METHODS: In a population-based
      study, we analyzed data from 280 mothers diagnosed with breast cancer at
      Sahlgrenska University Hospital in Gothenburg, Sweden. RESULTS: Of those who did
      not receive chemotherapy treatment, 70 out of 112 women (63 %) reported a desire
      to receive support about the worry about their children, and of those who
      received chemotherapy treatment, 20 out of 49 (41 %) reported a need for support
      immediately following diagnosis and before surgery. We identified having children
      at home (P < 0.0001), worry about sex life (P = 0.0009), fear of dying from
      breast cancer (P = 0.0055), and worried about one's personal financial situation
      (P = 0.0413) as the variables most closely related to worry about the children.
      CONCLUSIONS: Our population-based study shows that mothers with breast cancer had
      an immediate desire to receive psychosocial support regarding the worry about
      their own children. If we wish to shorten the pain associated with this worry
      among women diagnosed with breast cancer, it may be helpful to offer support as
      early in the disease trajectory as possible as it may reduce the risk of a later,
      more complicated, unnecessarily prolonged psychosocial rehabilitation process.

PMID- 24903259
TI  - Sustainable production of acrylic acid: alkali-ion exchanged beta zeolite for gas
      phase dehydration of lactic acid.
AB  - Gas-phase dehydration of lactic acid (LA) to acrylic acid (AA) was investigated
      over alkali-exchanged beta zeolite (M(x)Na(1-x)beta, M=Li(+), K(+), Rb(+), or
      Cs(+)) of different exchange degrees (x). The reaction was conducted under
      varying conditions to understand the catalyst selectivity for AA production and
      trends of byproduct formation. The nature and exchange degree of M(+) were found
      to be critical for the acid-base properties and catalytic performance of the
      exchanged zeolite. K(x)Na(1-x)beta of x=0.94 appeared to be the best performing
      catalyst whereas Li(x)Na(1-x)beta and Nabeta were the poorest in terms of AA
      selectivity and yield. The AA yield as high as 61 mol % (selectivity: 64 mol %)
      could be obtained under optimized reaction conditions for up to 8 h over the best
      performing K0.94Na0.06beta. The acid and base properties of the catalysts were
      probed, respectively by temperature-programmed desorption (TPD) of adsorbed NH3
      and CO2, and were related to the electrostatic potentials of the alkali ions in
      the zeolite, which provided a basis for the discussion of the acid-base catalysis
      for sustainable AA formation from LA.

PMID- 24903260
TI  - African perspectives on the need for global harmonisation of food safety
      regulations.
AB  - Africa is a large continent consisting of 54 countries at different levels of
      development and reflecting numerous diverse cultures. Africa's agricultural
      potential is largely untapped, with approximately 60% of the world's non
      cultivated arable land found in sub-Saharan Africa. Excluding South Africa, which
      is the largest economy in Africa and which has a well-established food sector
      with a substantial export market, economies in sub-Saharan Africa have been
      steadily growing at over 5% per annum. Whilst most African countries face many
      challenges, including weak infrastructure as well as political and economic
      instability, many changes are occurring, one of these being identifying specific
      commodities in a particular country which warrant substantial investment for
      growth into export opportunities. These opportunities create an immediate need
      for development of food standards, including food safety standards, based on
      scientific principles to enable regional and international trade in food, thereby
      assisting in ensuring Africa's role in the global food economy.

PMID- 24903261
TI  - Parenteral nutrition product is suspected as cause of 18 cases of septicaemia in
      neonates.

PMID- 24903262
TI  - Knowledge assessment regarding secondary prevention of coronary heart disease--a
      multi centre survey.
AB  - BACKGROUND: Cardiovascular Disease (CVD) is a major cause of mortality worldwide.
      Control and reduction of cardiovascular risk factors such as elevated blood
      pressure, high cholesterol levels, excess of body weight, smoking and lack of
      exercise can contribute to a reduction of CVD mortality. METHODS: A standardized
      questionnaire was administered to all medical officers willing to participate in
      the study, who were working in the Cardiology Units all over Sri Lanka to assess
      the source of continuous medical education, attitudes on secondary prevention,
      barriers to secondary prevention and knowledge assessment of secondary prevention
      of cardiovascular diseases. Chi square was used to compare groups and p < 0.05
      was considered significant. RESULTS: 132 participants with equal numbers of males
      and female doctors participated. While 56 doctors have had no training in
      cardiology, 75 doctors have had some training in a cardiology unit. The barriers
      for secondary prevention were, poor knowledge/understanding of patients 3.82
      (1.06), too many drugs 3.74 (0.98), presence of co-morbid conditions 3.68(0.97),
      cost of medications 3.69 (0.97) and poor adherence to prevention strategies by
      patients 3.44 (1.15). Routine clinic visits 85 (65%) and public awareness day
      seminars 30 (22.2%) were the most effective methods of secondary prevention.
      Guidelines were the most popular method of continuous medical education. Those
      who have had some training in cardiology did not differ in their knowledge from
      those who have never had training in cardiology. Knowledge about prevention with
      regard to diet was inadequate and exercise and lipids were adequate but not good.
      Rates of knowledge on smoking cessation were much higher than for other CVD risk
      factors. CONCLUSION: There needs to be more adherences to clinical guidelines and
      attention paid to CVD prevention, in particular, the importance of dietary
      modifications, adequate exercise, and lipid control.

PMID- 24903264
TI  - Lentigo maligna and lentigo maligna melanoma as occupational skin diseases in a
      forestry worker with long-standing occupational UV-exposure.

PMID- 24903263
TI  - Regulatory and coding genome regions are enriched for trait associated variants
      in dairy and beef cattle.
AB  - BACKGROUND: In livestock, as in humans, the number of genetic variants that can
      be tested for association with complex quantitative traits, or used in genomic
      predictions, is increasing exponentially as whole genome sequencing becomes more
      common. The power to identify variants associated with traits, particularly those
      of small effects, could be increased if certain regions of the genome were known
      a priori to be enriched for associations. Here, we investigate whether twelve
      genomic annotation classes were enriched or depleted for significant associations
      in genome wide association studies for complex traits in beef and dairy cattle.
      We also describe a variance component approach to determine the proportion of
      genetic variance captured by each annotation class. RESULTS: P-values from large
      GWAS using 700K SNP in both dairy and beef cattle were available for 11 and 10
      traits respectively. We found significant enrichment for trait associated
      variants (SNP significant in the GWAS) in the missense class along with regions 5
      kilobases upstream and downstream of coding genes. We found that the non-coding
      conserved regions (across mammals) were not enriched for trait associated
      variants. The results from the enrichment or depletion analysis were not in
      complete agreement with the results from variance component analysis, where the
      missense and synonymous classes gave the greatest increase in variance explained,
      while the upstream and downstream classes showed a more modest increase in the
      variance explained. CONCLUSION: Our results indicate that functional annotations
      could assist in prioritization of variants to a subset more likely to be
      associated with complex traits; including missense variants, and upstream and
      downstream regions. The differences in two sets of results (GWAS enrichment
      depletion versus variance component approaches) might be explained by the fact
      that the variance component approach has greater power to capture the cumulative
      effect of mutations of small effect, while the enrichment or depletion approach
      only captures the variants that are significant in GWAS, which is restricted to a
      limited number of common variants of moderate effects.

PMID- 24903265
TI  - A novel KIR2DL3*00110 allele identified in a southern Chinese Han individual.
AB  - KIR2DL3*00110 differs from KIR2DL3*00101 by a single silent mutation at coding
      sequence (CDS) nt618 A>C in exon 5.

PMID- 24903266
TI  - Novel thermally activated delayed fluorescence materials-thioxanthone derivatives
      and their applications for highly efficient OLEDs.
AB  - Thermally activated delayed fluorescence emitters with small energy gap between
      the triplet and singlet (DeltaEST ), TXO-PhCz and TXO-TPA, have been successfully
      synthesized by combining a hole-transporting TPA/PhCz moiety and an electron
      transporting TXO moiety. Both compounds display efficient solid-state
      luminescence with an efficient up-conversion of the triplet to singlet. OLEDs
      based on them exhibt high performance up to 21.5%, which is among the best
      reported for OLEDs. 

PMID- 24903268
TI  - Role of the autonomic nervous system and baroreflex in stress-evoked
      cardiovascular responses in rats.
AB  - Restraint stress (RS) is an experimental model to study stress-related
      cardiovascular responses, characterized by sustained pressor and tachycardiac
      responses. We used pharmacologic and surgical procedures to investigate the role
      played by sympathetic nervous system (SNS) and parasympathetic nervous system
      (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic
      blockade with pentolinium significantly reduced RS-evoked pressor and
      tachycardiac responses. Intravenous treatment with homatropine methyl bromide did
      not affect the pressor response but increased tachycardia. Pretreatment with
      prazosin reduced the pressor and increased the tachycardiac response.
      Pretreatment with atenolol did not affect the pressor response but reduced
      tachycardia. The combined treatment with atenolol and prazosin reduced both
      pressor and tachycardiac responses. Adrenal demedullation reduced the pressor
      response without affecting tachycardia. Sinoaortic denervation increased pressor
      and tachycardiac responses. The results indicate that: (1) the RS-evoked
      cardiovascular response is mediated by the autonomic nervous system without an
      important involvement of humoral factors; (2) hypertension results primarily from
      sympathovascular and sympathoadrenal activation, without a significant
      involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial
      peak in the hypertensive response to restraint is sympathovascular-mediated,
      whereas the less intense but sustained hypertensive response observed throughout
      the remaining restraint session is mainly mediated by sympathoadrenal activation
      and epinephrine release; (4) tachycardia results from CSNS activation, and not
      from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and
      heart rate changes are a vector of both influences; (6) the baroreflex is
      functional during restraint, and modulates both the vascular and cardiac
      responses to restraint.

PMID- 24903267
TI  - Managerial leadership for research use in nursing and allied health care
      professions: a narrative synthesis protocol.
AB  - BACKGROUND: Nurses and allied health care professionals (physiotherapists,
      occupational therapists, speech and language pathologists, dietitians) form more
      than half of the clinical health care workforce and play a central role in health
      service delivery. There is a potential to improve the quality of health care if
      these professionals routinely use research evidence to guide their clinical
      practice. However, the use of research evidence remains unpredictable and
      inconsistent. Leadership is consistently described in implementation research as
      critical to enhancing research use by health care professionals. However, this
      important literature has not yet been synthesized and there is a lack of clarity
      on what constitutes effective leadership for research use, or what kinds of
      intervention effectively develop leadership for the purpose of enabling and
      enhancing research use in clinical practice. We propose to synthesize the
      evidence on leadership behaviours amongst front line and senior managers that are
      associated with research evidence by nurses and allied health care professionals,
      and then determine the effectiveness of interventions that promote these
      behaviours. METHODS/DESIGN: Using an integrated knowledge translation approach
      that supports a partnership between researchers and knowledge users throughout
      the research process, we will follow principles of knowledge synthesis using a
      systematic method to synthesize different types of evidence involving: searching
      the literature, study selection, data extraction and quality assessment, and
      analysis. A narrative synthesis will be conducted to explore relationships within
      and across studies and meta-analysis will be performed if sufficient homogeneity
      exists across studies employing experimental randomized control trial designs.
      DISCUSSION: With the engagement of knowledge users in leadership and practice, we
      will synthesize the research from a broad range of disciplines to understand the
      key elements of leadership that supports and enables research use by health care
      practitioners, and how to develop leadership for the purpose of enhancing
      research use in clinical practice. TRIAL REGISTRATION: PROSPERO CRD42014007660.

PMID- 24903269
TI  - Associations of hair cortisol concentration with self-reported measures of stress
      and mental health-related factors in a pooled database of diverse community
      samples.
AB  - A pooled database from diverse community samples was used to examine the
      associations of hair cortisol concentration (HCC) with self-reported stress and
      stress-linked mental health measures, including depression, anxiety, alcohol and
      drug use, disability and experiences with aggression. As part of innovative
      research using a mobile laboratory to study community mental health, data were
      pooled from five sub-studies: a random sample of the general population (n = 70),
      people who had received treatment for a mental health and/or substance use
      problem (n = 78), family members of people treated for mental health and/or
      substance use problems (n = 49), community volunteers who sometimes felt sad or
      blue or thought they drank too much (n = 83) and young adults in intimate partner
      relationships (n = 44). All participants completed a computerized questionnaire
      including standard measures of perceived stress, chronic stress, depression,
      anxiety, hazardous drinking, tobacco use, prescription drug use, illicit drug
      use, disability and intimate partner aggression. HCC was significantly associated
      with use of antidepressants, hazardous drinking, smoking and disability after
      adjusting for sub-study and potential confounders (sex, body-mass index, use of
      glucocorticoids and hair dyed). In addition, preliminary analyses suggest a
      significant curvilinear relationship between HCC and perceived stress;
      specifically, HCC increased with higher perceived stress but decreased at the
      highest level of stress. Overall, HCC was associated with mental health-related
      variables mainly reflecting substance use or experiencing a disability. The
      relationship between HCC and self-reported stress is unclear and needs further
      research.

PMID- 24903270
TI  - Monoclonal antibodies: pharmacokinetics as a basis for new dosage regimens?
AB  - Complete monoclonal IgG antibodies which are in use in clinical practice share
      some pharmacological properties resulting in high concentrations in plasma. This
      fact is reflected in their low volumes of distribution, which can also be
      correlated with a high molecular weight and water solubility. This feature allows
      a novel approach to be applied to the dosing schedule for this group of drugs
      with fixed doses being used instead of the initially developed weight- or body
      surface-adjusted dosing schedules. In addition, the development of a new
      formulation containing hyaluronidase allows a subcutaneous route of
      administration to be used, because hyaluronidase creates a space in the
      subcutaneous tissue that helps antibody absorption. This method requires higher
      doses, but has allowed testing the feasibility of administering a fixed dose,
      with no individual dose adjustments based on weight or body surface. Moreover,
      loading doses are not needed, because the first dose results, within 3 weeks, in
      minimum concentrations that are higher than effective concentrations.

PMID- 24903271
TI  - Adherence to imatinib among patients attending Saskatchewan Cancer Agency
      Pharmacies.
AB  - RATIONALE: Chronic use of imatinib confers an important survival benefit for
      individuals with chronic myeloid leukemia. In Saskatchewan, the provincial cancer
      agency addresses important barriers to adherence by providing imatinib at no cost
      through specialized cancer centers. OBJECTIVE: To describe adherence to imatinib
      dispensed through the Saskatchewan Cancer Agency. STUDY DESIGN AND METHODS: We
      conducted a retrospective analysis of electronic pharmacy dispensation records
      from the Saskatchewan Cancer Agency. All dispensations for imatinib classified
      for hematologic malignancies were electronically abstracted by cancer center
      personnel and securely forwarded to investigators with all meaningful patient
      identifiers removed. All subjects receiving a new dispensation (i.e. using a 6
      month washout period) for imatinib between 1 June 2004 and 31 December 2011 were
      included. The primary endpoint was optimal adherence to imatinib during the first
      year of therapy, defined as a medication possession ratio >= 80%. RESULTS: Ninety
      one subjects were started on imatinib during the observation period. During the
      first year of therapy, 82.4% (75/91) maintained a medication possession ratio >=
      80%. The percentage of individuals maintaining optimal adherence decreased only
      slightly when the observation period was extended to 2 (78.4%) or 3 years
      (78.8%). CONCLUSIONS: Non-adherence to imatinib is relatively infrequent when
      provided by the Saskatchewan Cancer Agency.

PMID- 24903272
TI  - Is there any cumulative dose for trastuzumab?
AB  - Trastuzumab is one of the most important agents that target human epidermal
      growth factor receptor 2, but its cardiotoxic effect limits to use it. The
      mechanism of cardiac dysfunction-related trastuzumab is still unclear. In
      literature, there is no definite information about the cumulative dose of
      trastuzumab for cardiotoxicity. In presented case, we reported a breast cancer
      patient who has been receiving long-term trastuzumab. We have not found any
      cardiac problems for duration of over four years. According to our case and
      literature review, we may say that trastuzumab is safely used with periodically
      echocardiographic control in patients with breast cancer. 

PMID- 24903273
TI  - Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and
      confers resistance to MET-targeted therapy.
AB  - The tyrosine kinase encoded by the MET oncogene is activated by gene mutation or
      amplification in tumors, which in most instances maintain addiction, i.e.,
      dependency, to MET activation. This makes MET an attractive candidate for
      targeted therapies. Here we show that, in 3/3 MET-addicted human gastric cancer
      cell lines, MET kinase inhibition resulted in a 3- to 4-fold increased expression
      of the antiapoptotic small heat-shock protein of 27 kDa (HSP27, HSPB1). HSP27
      increase depended on the inhibition of the MEK/ERK pathway and on heat-shock
      factor 1 (HSF1) and hypoxia-inducible factor-1alpha (HIF-1alpha) regulation.
      Importantly, HSP27-silenced MET-addicted cells underwent 2- and 3-fold more
      apoptosis following MET inhibition in vitro and in vivo, respectively. Likewise,
      in human cancer cells susceptible to epidermal growth factor receptor (EGFR)
      inhibition, EGFR inhibitors induced HSP27 expression and were strengthened by
      HSP27 suppression. In control cell lines that were not affected by drugs
      targeting MET or EGFR, these drugs did not induce HSP27 increase. Therefore, in
      cancer therapies targeting the MET pathway, the induction of HSP27 might limit
      the efficacy of anti-MET agents. As HSP27 increase also impairs the effectiveness
      of EGFR inhibitors and is known to protect cells from chemotherapeutics, the
      induction of HSP27 by targeted agents might strongly affect the success of
      combination treatments.

PMID- 24903274
TI  - Rac1 GTPase silencing counteracts microgravity-induced effects on osteoblastic
      cells.
AB  - Bone cells exposed to real microgravity display alterations of their cytoskeleton
      and focal adhesions, two major mechanosensitive structures. These structures are
      controlled by small GTPases of the Ras homology (Rho) family. We investigated the
      effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under
      microgravity conditions. Human MG-63 osteoblast-like cells silenced for
      RhoGTPases were cultured in the automated Biobox bioreactor (European Space
      Agency) aboard the Foton M3 satellite and compared to replicate ground-based
      controls. The cells were fixed after 69 h of microgravity exposure for postflight
      analysis of focal contacts, F-actin polymerization, vascular endothelial growth
      factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did
      not affect sensitivity to microgravity but that Rac1 and, to a lesser extent,
      Cdc42 abrogation was particularly efficient in counteracting the spaceflight
      related reduction of the number of focal contacts [-50% in silenced, scrambled
      (SiScr) controls vs. -15% for SiRac1], the number of F-actin fibers (-60% in
      SiScr controls vs. -10% for SiRac1), and the depletion of matrix-bound VEGF (-40%
      in SiScr controls vs. -8% for SiRac1). Collectively, these data point out the
      role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated
      signaling pathways as potential targets for counteracting microgravity effects.

PMID- 24903275
TI  - miR-21 normalizes vascular smooth muscle proliferation and improves coronary
      collateral growth in metabolic syndrome.
AB  - Inadequate cell proliferation is considered a major causative factor for impaired
      coronary collateral growth (CCG). Proangiogenic growth factors (GFs) stimulate
      cell proliferation, but their administration does not promote CCG in patients.
      These GFs are increased in patients with metabolic syndrome and in animal models,
      where CCG is impaired. Here, we investigated whether excessive cell proliferation
      underlies impaired CCG in metabolic syndrome. Normal [Sprague-Dawley (SD)] and
      metabolic syndrome [James C. Russell (JCR)] rats underwent repetitive ischemia
      (RI; transient, repetitive coronary artery occlusion and myocardial ischemia). We
      have shown that CCG was maximal at d 9 of RI in SD rats but did not occur in JCR
      rats. The increase in cell proliferation (PCNA, Ki-67, cyclin A, phospho- cdc2,
      p21Waf, p27Kip) was transient (~4-fold, d 3 RI) in SD rats but greater and
      sustained in JCR rats (~8- to 6-fold, d 3-9 RI). In JCR rats, this was associated
      with increased and sustained miR-21 expression and accumulation of proliferating
      synthetic vascular smooth muscle cells in the lumen of small arterioles, which
      failed to undergo outward expansion. Administration of anti-miR-21 blocked RI
      induced cell proliferation and significantly improved CCG in JCR rats (~60%). miR
      21-dependent excessive cell proliferation in the later stages of collateral
      remodeling correlates with impaired CCG in metabolic syndrome.

PMID- 24903277
TI  - Perceptions of the Previously Convicted: The Influence of Conviction Type and
      Therapy Participation.
AB  - The present study explores individuals' desires for social distance from violent
      versus non-violent offenders and investigates whether disclosure of the
      offender's therapy completion influences this desire for distance. The study also
      investigates relationships between participants' desires for social distance and
      their perceptions of therapy effectiveness with offenders. Using a 2 * 2
      factorial design, 150 undergraduate participants completed measures of social
      distance and perceived offender therapy effectiveness. Overall, respondents
      indicated higher desires for social distance from offenders convicted of violent
      versus non-violent crimes. Respondents also reported lower desire for social
      distance when the offenders reported completing therapy, even when their
      perception of therapy effectiveness was low. The results of this study have
      implications for treatment development. Results attest to the value of preparing
      incarcerated offenders with an accurate expectation of levels and patterns of
      stigma to be faced upon release and also speak to the value of disclosing
      treatment completion, especially in the context of healthy interpersonal
      relationship development and maintenance. 

PMID- 24903276
TI  - Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in
      diabetes: a novel biomarker for early diagnosis.
AB  - Diabetic retinopathy (DR) is a microvascular complication of diabetes and a
      leading cause of vision loss. Biomarkers and methods for early diagnosis of DR
      are urgently needed. Using a new molecular imaging approach, we show up to 94%
      higher accumulation of custom designed imaging probes against vascular
      endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels
      of diabetic animals (P<0.01), compared to normal controls. More than 80% of the
      VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal
      controls (P<0.01). Angiography in rabbit retinas revealed microvascular
      capillaries to be the location for VEGF-A-induced leakage, as expressed by
      significantly higher rate of fluorophore spreading with VEGF-A injection when
      compared to vehicle control (26+/-2 vs. 3+/-1 MUm/s, P<0.05).
      Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals
      but not in normal controls. Macular vessels from diabetic patients (n=7) showed
      significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral
      retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a
      new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2
      could become a key diagnostic target, one that might help to prevent retinal
      vascular leakage and proliferation in diabetic patients.

PMID- 24903278
TI  - Retrospective correction of physiological field fluctuations in high-field brain
      MRI using concurrent field monitoring.
AB  - PURPOSE: Magnetic field fluctuations caused by subject motion, such as breathing
      or limb motion, can degrade image quality in brain MRI, especially at high field
      strengths. The purpose of this study was to investigate the feasibility of
      retrospectively correcting for such physiological field perturbations based on
      concurrent field monitoring. THEORY AND METHODS: High-resolution T2*-weighted
      gradient-echo images of the brain were acquired at 7T with subjects performing
      different breathing and hand movement patterns. Field monitoring with a set of
      (19) F NMR probes distributed around the head was performed in two variants:
      concurrently with imaging or as a single field measurement per readout. The
      measured field fluctuations were then accounted for in the image reconstruction.
      RESULTS: Significant field fluctuations due to motion were observed in all
      subjects, resulting in severe artifacts in uncorrected images. The artifacts were
      largely removed by reconstruction based on field monitoring. Accounting for field
      perturbations up to the 1st spatial order was generally sufficient to recover
      good image quality. CONCLUSIONS: It has been demonstrated that artifacts due to
      physiologically induced dynamic field perturbations can be greatly reduced by
      retrospective image correction based on field monitoring. The necessity to
      perform such correction is greatest at high fields and for field-sensitive
      techniques such as T2*-weighted imaging.

PMID- 24903279
TI  - Bacteria associated with truffle-fruiting bodies contribute to truffle aroma.
AB  - Truffles, symbiotic fungi renown for the captivating aroma of their fruiting
      bodies, are colonized by a complex bacterial community of unknown function. We
      characterized the bacterial community of the white truffle Tuber borchii and
      tested the involvement of its microbiome in the production of sulphur-containing
      volatiles. We found that sulphur-containing volatiles such as thiophene
      derivatives, characteristic of T. borchii fruiting bodies, resulted from the
      biotransformation of non-volatile precursor(s) into volatile compounds by
      bacteria. The bacterial community of T. borchii was dominated by alpha- and beta
      Proteobacteria. Interestingly, all bacteria phyla/classes tested in this study
      were able to produce thiophene volatiles from T. borchii fruiting body extract,
      irrespective of their isolation source (truffle or other sources). This indicates
      that the ability to produce thiophene volatiles might be widespread among
      bacteria and possibly linked to primary metabolism. Treatment of fruiting bodies
      with antibacterial agents fully suppressed the production of thiophene volatiles
      while fungicides had no inhibitory effect. This suggests that during the sexual
      stage of truffles, thiophene volatiles are exclusively synthesized by bacteria
      and not by the truffle. At this stage, the origin of thiophenes precursor in T.
      borchii remains elusive and the involvement of yeasts or other bacteria cannot be
      excluded. 

PMID- 24903280
TI  - In vitro and in vivo pharmacological characterization of nociceptin/orphanin FQ
      tetrabranched derivatives.
AB  - BACKGROUND AND PURPOSE: An innovative chemical approach, named peptide welding
      technology (PWT), allows the synthesis of multibranched peptides with
      extraordinary high yield, purity and reproducibility. With this approach, three
      different tetrabranched derivatives of nociceptin/orphanin FQ (N/OFQ) have been
      synthesized and named PWT1-N/OFQ, PWT2-N/OFQ and PWT3-N/OFQ. In the present study
      we investigated the in vitro and in vivo pharmacological profile of PWT N/OFQ
      derivatives and compared their actions with those of the naturally occurring
      peptide. EXPERIMENTAL APPROACH: The following in vitro assays were used: receptor
      and [(35)S]-GTPgammaS binding, calcium mobilization in cells expressing the human
      N/OFQ peptide (NOP) receptor, or classical opioid receptors and chimeric G
      proteins, electrically stimulated mouse vas deferens bioassay. In vivo
      experiments were performed; locomotor activity was measured in normal mice and in
      animals with the NOP receptor gene knocked out [NOP(-/-)]. KEY RESULTS: In vitro
      PWT derivatives of N/OFQ behaved as high affinity potent and rather selective
      full agonists at human recombinant and animal native NOP receptors. In vivo PWT
      derivatives mimicked the inhibitory effects exerted by the natural peptide on
      locomotor activity showing 40-fold higher potency and extremely longer lasting
      action. The effects of PWT2-N/OFQ were no longer evident in NOP(-/-) mice.
      CONCLUSIONS AND IMPLICATIONS: The results showed that the PWT can be successfully
      applied to the peptide sequence of N/OFQ to generate tetrabranched derivatives
      characterized by a pharmacological profile similar to the native peptide and
      associated with a higher potency and marked prolongation of action in vivo.

PMID- 24903281
TI  - Right or flawed: relationship obsessions and sexual satisfaction.
AB  - INTRODUCTION: Relationship obsessive-compulsive disorder (ROCD) is marked by the
      presence of obsessions and compulsions focusing on romantic relationships. ROCD
      symptoms were previously linked with decreased relationship quality and might
      interfere with sexual functioning. AIM: The study aims to examine the association
      between ROCD symptoms and sexual satisfaction. METHODS: Participants completed an
      online survey assessing ROCD symptoms and relationship and sexual satisfaction
      levels. Depression, general worry, obsessive-compulsive disorder (OCD) symptoms,
      and attachment orientation were also measured. MAIN OUTCOME MEASURE: The main
      outcome measures were self reported relationship satisfaction and sexual
      satisfaction. RESULTS: ROCD symptoms were associated with decreased sexual
      satisfaction over and above symptoms of depression, general worry, OCD, and
      attachment orientation. The link between ROCD symptoms and sexual satisfaction
      was mediated by relationship satisfaction. CONCLUSIONS: Identifying and
      addressing ROCD symptoms may be important for treatment of sexual functioning.

PMID- 24903282
TI  - Theoretical and experimental study of the role of cell-cell dipole interaction in
      dielectrophoretic devices: application to polynomial electrodes.
AB  - BACKGROUND: We aimed to investigate the effect of cell-cell dipole interactions
      in the equilibrium distributions in dielectrophoretic devices. METHODS: We used a
      three dimensional coupled Monte Carlo-Poisson method to theoretically study the
      final distribution of a system of uncharged polarizable particles suspended in a
      static liquid medium under the action of an oscillating non-uniform electric
      field generated by polynomial electrodes. The simulated distributions have been
      compared with experimental ones observed in the case of MDA-MB-231 cells in the
      same operating conditions. RESULTS: The real and simulated distributions are
      consistent. In both cases the cells distribution near the electrodes is dominated
      by cell-cell dipole interactions which generate long chains. CONCLUSIONS: The
      agreement between real and simulated cells' distributions demonstrate the
      method's reliability. The distribution are dominated by cell-cell dipole
      interactions even at low density regimes (105 cell/ml). An improved estimate for
      the density threshold governing the interaction free regime is suggested.

PMID- 24903283
TI  - Actuating porous polyimide films.
AB  - We report a novel method for the fabrication of one-component self-folding
      polymer films. The approach is based on films with a vertical gradient of
      porosity and was demonstrated on an example of porous polyimide films. The
      inhomogeneous porosity of the films was achieved through the implementation of
      capillary forces and gravity during the drying of a dispersion of colloidal
      particles in a solution of polymer precursor. As a result, three-layered films
      were formed. A monolayer of particles comprises the top layer, the second layer
      is the pure polymer, and the third layer is formed by a mixture of particles and
      polymer. Etching out the particles leaves polyimide film with inhomogeneous
      distributed pores. These porous polymer films roll and form tubes in organic
      solvents as well as their vapors and reversibly unfold in air. The obtained films
      were used for design of actuators, which are able to capture and release
      different objects through the reversible folding. 

PMID- 24903284
TI  - The two forms of alcohol brief intervention: an uneasy coalition.

PMID- 24903285
TI  - Lost in translation: The perils of implementing alcohol brief intervention when
      there are gaps in evidence and its interpretation.

PMID- 24903286
TI  - Motivational interventions may have greater sustained impact if they trained
      imagery-based self-management.

PMID- 24903287
TI  - Big issues.

PMID- 24903288
TI  - Commentary on Schwartz et al. (2014): Where next for face-to-face, person-to
      person, computerized and online brief interventions for drug users?

PMID- 24903289
TI  - Commentary on van der Pol et al. (2014): Reconsidering the association between
      cannabis exposure and dependence.

PMID- 24903290
TI  - Commentary on Lorains et al. (2014): a potentially important advance is
      understanding different types of gamblers.

PMID- 24903292
TI  - Commentary on Vink et al. (2014): The polygenic basis of drug use-does context
      matter?

PMID- 24903293
TI  - Commentary on Pedersen & von Soest (2014): Increasing snus use among Norwegian
      adolescents--evidence of harm reduction effects?

PMID- 24903294
TI  - Commentary on Lee et al. (2014): Betel-quid-when East encounters West.

PMID- 24903295
TI  - Juha Partanen (1936-2013).

PMID- 24903296
TI  - Addiction editors respond to Mr. Leverton.

PMID- 24903297
TI  - Letter from the Global Alcohol Producers Group.

PMID- 24903298
TI  - African experience supports view that the global alcohol industry should have no
      role in the formulation of public health policies.

PMID- 24903299
TI  - Skirmishes.

PMID- 24903300
TI  - Observations on industry involvement in public health policy in Asia-Pacific.

PMID- 24903301
TI  - The alcohol industry and the World Cup in Brazil.

PMID- 24903302
TI  - Animal Farm must give way to doublethink when studying addiction.

PMID- 24903303
TI  - Regulation of e-cigarettes in U.S.A.

PMID- 24903304
TI  - Severity of psychotic episodes in predicting concurrent depressive and anxiety
      features in acute phase schizophrenia.
AB  - BACKGROUND: Considering that depressive and anxiety symptoms are common in
      schizophrenia, this study investigated whether the severity of a psychotic
      episode in an acute phase schizophrenia cohort is predictive of concurrent
      depressive and anxiety features. METHOD: Fifty one recently hospitalised patients
      suffering from acute phase schizophrenia participated prospectively in a cross
      sectional study. The severity of the psychotic episode, the depressive features
      and the anxiety features were measured by the Structured Clinical Interview for
      Positive and Negative Syndrome Scale (SCI-PANSS), the Calgary Depression Scale
      for Schizophrenia (CDSS), the Hamilton Anxiety Rating Scale (HAM-A) and the
      Staden Schizophrenia Anxiety Rating Scale (S-SARS). The total SCI-PANSS-scores
      were adjusted to exclude appropriately the depression or anxiety items contained
      therein. To examine akathisia as potential confounder, the Barnes Akathisia Scale
      was also applied. The relationships were examined using linear regressions and
      paired t-tests were performed between lower and higher scores on the SCI-PANSS.
      RESULTS: A higher adjusted total SCI-PANSS-score predicted statistically
      significantly higher scores for depressive features on the CDSS (p < 0.0001) and
      for anxiety features on the HAM-A (p = 0.05) and the S-SARS (p < 0.0001). The
      group that scored more or equal to the median (=99) of the adjusted total SCI
      PANSS, scored significantly higher (p < 0.0001) on the CDSS, the HAM-A and the S
      SARS than the group scoring below it. Akathisia measured distinctly different (p
      < 0.0001) from both the anxiety measures. CONCLUSION: The study suggests that the
      severity of a psychotic episode in acute phase schizophrenia predicts the
      severity of concurrent depressive and anxiety features respectively.

PMID- 24903306
TI  - Does prior valve surgery change outcome in patients treated with cardiac
      resynchronization therapy?
AB  - AIMS: Cardiac valve surgery (CVS) has been implicated as a potential barrier to
      optimal response after cardiac resynchronization therapy (CRT) though prospective
      data regarding outcome remains limited. We sought to determine CRT response in
      patients with a prior history of CVS. METHODS AND RESULTS: We performed a
      retrospective analysis of a prospectively acquired cohort of CRT patients with
      history of CVS. Echocardiographic response was evaluated at baseline and 6
      months. The coprimary endpoints were time to first heart failure (HF)
      hospitalization and a composite of all-cause mortality, transplantation and left
      ventricular assist device (LVAD) assessed over a 3-year follow-up period. The
      study group consisted of 569 patients undergoing CRT. Of these, 86 patients had a
      history of CVS (46.5% aortic, 37.2% mitral, 16.3% combined, and tricuspid), and
      were compared to 483 patients with no history of CVS. Baseline clinical and
      echocardiographic characteristics were not significantly different between the
      groups except for a higher incidence of atrial fibrillation (AF; 74.4% vs. 55.3%;
      P = 0.001), coronary artery bypass surgery (CABG; 58.1% vs. 38.7%; P = 0.001),
      and longer QRS duration (167.6 +/- 29.3 milliseconds vs. 159.4 +/- 27.5
      milliseconds; P = 0.01) in those with prior CVS. Survival with respect to HF
      hospitalization and composite outcome was comparable in both groups.
      Echocardiographic response (improvement in left ventricular ejection fraction of
      >=10%) was similar. No difference in clinical or echocardiographic outcome was
      found by type of valve surgery performed. CONCLUSION: Despite a higher incidence
      of AF, CABG, and longer QRS duration, history of CVS is not associated with worse
      clinical or echocardiographic outcome after CRT.

PMID- 24903305
TI  - ATF6 mediates a pro-inflammatory synergy between ER stress and TLR activation in
      the pathogenesis of liver ischemia-reperfusion injury.
AB  - Although the roles of the metabolic stress in organ ischemia-reperfusion injury
      (IRI) have been well recognized, the question of whether and how these stress
      responses regulate innate immune activation against IR remains unclear. In a
      murine liver partial warm ischemia mode, we showed that prolonged ischemia
      triggered endoplasmic reticulum (ER) stress response, particularly, the
      activating transcription factor 6 (ATF6) branch, in liver Kupffer cells (KCs) and
      altered their responsiveness against Toll-like receptor (TLR) stimulation.
      Ischemia-primed cells increased pro-, but decreased anti-, inflammatory cytokine
      productions. Alleviation of ER stress in vivo by small chemical chaperon 4
      phenylbutyrate or ATF6 small interfering RNA (siRNA) diminished the pro
      inflammatory priming effect of ischemia in KCs, leading to the inhibition of
      liver immune response against IR and protection of livers from IRI. In vitro,
      ATF6 siRNA abrogated the ER stress-mediated pro-inflammatory enhancement of
      macrophage TLR4 response, by restricting NF-kappaB and restoring Akt activations.
      Thus, ischemia primes liver innate immune cells by ATF6-mediated ER stress
      response. The IR-induced metabolic stress and TLR activation function in synergy
      to activate tissue inflammatory immune response. 

PMID- 24903307
TI  - Drug development: EU paediatric legislation, the European Medicines Agency and
      its Paediatric Committee--adolescents' melanoma as a paradigm.
AB  - The European Medicines Agency (EMA) website lists all diseases that officially
      exist in adults only. The class waiver for juvenile melanoma was revoked in 2008
      referring to US SEER statistics. This statistical justification is misleading.
      Melanoma in adolescents is much rarer than claimed by EMA/Paediatric Committee; <
      1 / 4 of adolescents with melanoma need systemic treatment; separate efficacy
      studies are neither medically justified nor feasible. The scarce adolescent
      patients should be allowed to participate in adult trials. To force companies to
      investigate them separately turns them into paediatric hostages, to adapt the
      term therapeutic orphans coined in 1968 by Shirkey. There are now five melanoma
      Paediatric Investigation Plans (PIPs). Probably none of the PIP-triggered
      clinical studies will ever be completed; we propose to call them ghost studies.
      An oncology research network considering a reasonable trial in melanoma,
      including adolescents, will compete for recruitment with the PIP-triggered trials
      designed by regulatory tunnel vision and sponsored by companies under EMA-imposed
      pressure. EMA/Paediatric Committee's territorial enthusiasm ("our patients")
      damages oncology research.

PMID- 24903308
TI  - Microbial fuel cells - Applications for generation of electrical power and
      beyond.
AB  - A Microbial Fuel Cell is a bioelectrochemical device that exploits metabolic
      activities of living microorganisms for generation of electric current. The
      usefulness and unique and exclusive architecture of this device has received wide
      attention recently of engineers and researchers of various disciplines such as
      microbiologists, chemical engineers, biotechnologists, environment engineers and
      mechanical engineers, and the subject of MFCs has thereby progressed as a well
      developed technology. Sustained innovations and continuous development efforts
      have established the usefulness of MFCs towards many specialized and value-added
      applications beyond electricity generation, such as wastewater treatment and
      implantable body devices. This review is an attempt to provide an update on this
      rapidly growing technology. 

PMID- 24903310
TI  - Commentary on: Editorial Successful failure: good for the self and science. Clark
      A.M. & Thompson D. (2013) Journal of Advanced Nursing 69(10): 2145-2147.

PMID- 24903309
TI  - MicroRNA-135a acts as a putative tumor suppressor by directly targeting very low
      density lipoprotein receptor in human gallbladder cancer.
AB  - The precise functions and mechanisms of microRNAs (miR) in gallbladder cancer
      (GBC) remain elusive. In this study, we found that miR-135a-5p expression is
      often dampened and correlated with neoplasm histologic grade in GBC. MicroRNA
      135a-5p introduction clearly inhibited GBC cell proliferation in vitro and in
      vivo. Moreover, very low density lipoprotein receptor (VLDLR), which is often
      upregulated in GBC tissues, was identified as a direct functional target of miR
      135a-5p. Furthermore, the p38 MAPK pathway was proven to be involved in miR-135a
      VLDLR downstream signaling. Together, these results suggested that the miR-135a
      VLDLR-p38 axis may contribute to GBC cell proliferation. 

PMID- 24903312
TI  - Outcome analysis of morcellation craniotomy with distraction osteogenesis for
      scaphocephaly.
AB  - BACKGROUND: Techniques for sagittal synostosis correction continue to evolve,
      thus resulting in improved outcomes and minimized morbidity. Spring-assisted
      cranioplasty and strip craniotomy with postoperative helmet usage are simple
      minimally invasive surgeries. However, these procedures are only useful in
      younger patients (generally up to 9 months of age); older children usually
      undergo total cranial remodeling, which is more stressful. We have developed a
      procedure combining morcellation craniotomy with distraction osteogenesis (MoD),
      which we have been performing since 2000. Here, we describe and evaluate this
      method of treatment. METHODS: Seven patients who underwent MoD for isolated
      sagittal synostosis were followed for 10 years postoperatively. The control group
      consisted of 7 patients who had undergone total cranial remodeling in the period
      immediately preceding the MoD operations. Cephalography, clinical examinations,
      medical record data and medical photographs were used to evaluate and compare the
      2 groups. RESULTS: In comparison with total cranial remodeling, the MoD procedure
      resulted in a significantly shorter mean operation time and a significantly lower
      mean blood transfusion volume. The postoperative cephalic index was not
      significantly different between the MoD (75.8 +/- 0.9) and the control groups
      (75.6 +/- 1.4), and satisfactory cranial shape volumes were achieved without
      serious complications. CONCLUSION: The MoD procedure is a safe, effective and
      reliable technique for dynamic total skull remodeling with minimal morbidity. It
      can be used to improve upon previous surgical concepts for treating
      scaphocephaly, particularly in older patients.

PMID- 24903313
TI  - The Hidradenitis Suppurativa Priority Setting Partnership.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) has been neglected by medical
      researchers and society in general, despite being a relatively common, painful,
      chronic skin disease. OBJECTIVES: To generate a top 10 list of HS research
      priorities, from the perspectives of patients with HS, carers and clinicians, to
      take to funding bodies. METHODS: A priority setting partnership was established
      between patients with HS, carers and clinicians, following the James Lind
      Alliance process. Survey 1 requested submission of HS uncertainties, which were
      grouped into 'indicative uncertainties' for prioritization in survey 2. The 30
      highest-ranked indicative uncertainties were reduced to a 'top 10' list using
      nominal group technique at a prioritization workshop attended by all relevant HS
      stakeholders. RESULTS: In total 1495 potential uncertainties were submitted in
      survey 1, including 57% from patients with HS and carers, and grouped into 55
      indicative uncertainties. Ranking in survey 2 was completed by 371 participants,
      50% of whom were patients and carers. The final workshop was attended by 22 HS
      stakeholders and four facilitators and produced a top 10 list, the three highest
      priorities in descending order being (i) What is the most effective and safe
      group of oral treatments in treating HS? (ii) What is the best management of an
      acute flare? (iii)What is the impact of HS and its treatment on people with HS?
      CONCLUSIONS: The top 10 HS research priorities have been directly disseminated to
      funders to raise awareness of HS. The next step is to generate research questions
      that will provide the evidence needed to improve care for patients with HS.

PMID- 24903314
TI  - Predictors of mortality in acute heart failure: interaction between diabetes and
      impaired left ventricular ejection fraction.
AB  - AIM: The aim of this study was to test the hypothesis that diabetes modifies the
      risk of mortality in acute heart failure patients, especially in patients with
      impaired LVEF, and that impaired LVEF in turn modifies the risk of mortality in
      diabetic patients. METHODS AND RESULTS: We studied 2121 patients with acute heart
      failure admitted at two centres in Singapore from 1 January 2008 to 31 December
      2009. The date of the last follow-up was 31 December 2011, with a median follow
      up time (interquartile range) of 914 (442-1190) days. Cox regression was used to
      estimate hazard ratios for all-cause mortality in patients with LVEF >=50%, LVEF
      30-49%, and LVEF <30% relative to diabetic status. Impaired LVEF (<50%) in the
      presence of diabetes substantially increased the risk of mortality compared with
      non-diabetics with LVEF <50%. The adjusted hazard ratio (aHR) and 95% confidence
      interval (CI) for diabetic patients with an LVEF of 30-49% (1.46, 95% 1.18-1.81)
      was not statistically different from the aHR in non-diabetic patients with
      severely impaired LVEF of <30% (1.38, 95% CI 1.09-1.75) (P = 0.644). The
      deleterious effects of diabetes seemed to be confined to acute heart failure
      patients with impaired LVEF, as the mortality rate in patients with LVEF >50% was
      not increased. Other clinical predictors of mortality were ageing, prior
      myocardial infarction, systolic blood pressure >140 mmHg, creatinine >=250
      umol/L, haemoglobin <9.0 g/dL, and prior stroke/transient ischaemic attack.
      CONCLUSION: The interaction of diabetes and impaired LVEF in acute heart failure
      patients significantly amplifies the deleterious effects of each as distinct
      disease entities.

PMID- 24903315
TI  - A retrospective study on the aetiology, management, and outcome of brain abscess
      in an 11-year, single-centre study from China.
AB  - BACKGROUND: Brain abscesses continue to pose diagnostic and therapeutic
      challenges in developed and developing countries. Their aetiology and management
      remain complex and unclear, making improvement of treatments and outcome
      difficult. METHODS: To determine the demographics, management, and the variables
      that affect the outcome in subjects with brain abscesses treated at a single
      centre over an 11-year period, we retrospectively analysed data in 60 patients
      with brain abscesses surgically treated with stereotactically guided aspiration
      or open craniotomy excision in Shanghai Changzheng Hospital between January 2001
      and December 2011. Such variables as age, gender, Glasgow Coma Scale (GCS) score
      at admission, clinical presentation, location, number of lesions, predisposing
      factors, mechanism of infection, aetiological agent, and therapy were analysed
      independently. RESULTS: Our analysis demonstrated that patient age and gender
      were factors that influence the occurrence of brain abscess; female patients and
      patients greater than 40 years of age were most likely to suffer a brain abscess.
      We also found that a patient's GCS score upon admission did not influence
      outcome. While frequency of successful culturing of the infectious agent was low,
      positive cultures were obtained in only 8 of the cases (13.33%), in which the
      most common isolate was Streptococcus milleri. Outcome was favourable in 78.33%
      of the subjects, while the mortality rate was 20%. The outcome of one patient was
      poor due to the abscess in the basal ganglia region. CONCLUSIONS:
      Stereotactically guided aspiration is an effective treatment for brain abscess
      with an overall favourable outcome. Mortality due to brain abscess was not
      directly related to surgery nor surgical technique. Additional studies will
      continue to reveal patients trends that may improve treatment for brain abscess.

PMID- 24903316
TI  - Feasibility and diagnostic accuracy of early mood screening to diagnose
      persisting clinical depression/anxiety disorder after stroke.
AB  - BACKGROUND: Depression/anxiety disorders are common after stroke and have a
      negative impact on outcomes. Guidelines recommend that all stroke survivors are
      screened for these problems. However, there is no consensus on timing or method
      of assessment. We investigated the feasibility and accuracy of a very early
      screening strategy and the diagnostic accuracy this has for depression/anxiety
      disorders at 1 month. METHODS: Screening tools were Hospital Anxiety and
      Depression Scale (HADS) and Depression Intensity Scale Circles (DISCs); we also
      assessed cognition using the Montreal Cognitive Assessment (MoCA). Screening was
      offered to sequential stroke admissions. At 1 month we assessed for clinical
      depression/anxiety disorder using Mini-International Neuropsychiatric Interview
      (MINI) and retested screening tools. We described test accuracy of acute
      depression/anxiety screening for clinical diagnosis of depression/anxiety
      disorder at 1 month and described temporal change in screening test scores. We
      assessed feasibility by describing proportions that were able, agreed to and
      completed the screening tests. RESULTS: Over 4 months, 102/146 admissions were
      suitable for screening following initial medical assessment, 69 (68%) agreed to
      screening, of whom 33 (48%) required researcher assistance to complete the
      screening test battery. Median time to assessment was 2 days (IQR: 1-4). Early
      HADS suggested n = 9 (13%) with depression; DISCs n = 25 (37%). Median acute MoCA
      was 21/30. At 1 month, n = 61 (88%) provided data. Repeat scores showed
      improvement over time; HADS (anxiety) mean difference: 2.5 (95% CI: 1.2-3.7),
      HADS (depression) mean difference: 1.6 (95% CI: 0.3-2.9). MINI defined n = 12
      (20%) with depression and n = 6 (10%) with anxiety disorder. Comparing baseline
      screening to 1-month clinical diagnosis, HADS sensitivity was 0.25 (95% CI: 0.09
      0.53) and specificity 0.94 (95% CI: 0.84-0.98); DISCs sensitivity was 0.92 (95%
      CI: 0.65-0.99) and specificity 0.78 (95% CI: 0.64-0.87). CONCLUSIONS: Even
      amongst 'medically stable' stroke patients, depression/anxiety screening at the
      acute stage may not be feasible or accurate. Half of participants required
      assistance from the researcher to complete assessments. The poor predictive
      accuracy of HADS for depression/anxiety disorder at 1 month may be due in part to
      the high prevalence of cognitive impairment in our sample. Screening in the first
      few days after stroke does not appear useful for detecting clinically important
      and sustained depression/anxiety problems.

PMID- 24903322
TI  - Personality, psychosocial and health-related predictors of quality of life in old
      age.
AB  - OBJECTIVES: Beyond its well-documented association with depressive symptoms
      across the lifespan, at an individual level, quality of life may be determined by
      multiple factors: psychosocial characteristics, current physical health and long
      term personality traits. METHOD: Quality of life was assessed in two distinct
      community-based age groups (89 young adults aged 36.2 +/- 6.3 and 92 older adults
      aged 70.4 +/- 5.5 years), each group equally including adults with and without
      acute depressive symptoms. Regression models were applied to explore the
      association between quality of life assessed with the World Health Organization
      Quality of Life - Bref (WHOQOL-Bref) and depression severity, education, social
      support, physical illness, as well as personality dimensions as defined by the
      Five-Factor Model. RESULTS: In young age, higher quality of life was uniquely
      associated with lower severity of depressive symptoms. In contrast, in old age,
      higher quality of life was related to both lower levels of depressive mood and of
      physical illness. In this age group, a positive association was also found
      between quality of life and higher levels of Openness to experience and
      Agreeableness personality dimensions. CONCLUSION: Our data indicated that, in
      contrast to young cohorts, where acute depression is the main determinant of poor
      quality of life, physical illness and personality dimensions represent additional
      independent predictors of this variable in old age. This observation points to
      the need for concomitant consideration of physical and psychological determinants
      of quality of life in old age.

PMID- 24903323
TI  - Effect of football or strength training on functional ability and physical
      performance in untrained old men.
AB  - The effects of 16 weeks of football or strength training on performance and
      functional ability were investigated in 26 (68.2 +/- 3.2 years) untrained men
      randomized into a football (FG; n = 9), a strength training (ST; n = 9), or a
      control group (CO; n = 8). FG and ST trained 1.6 +/- 0.1 and 1.5 +/- 0.1 times
      per week, respectively, with higher (P < 0.05) average heart rate (HR) (~140 vs
      100 bpm) and time >90%HRmax (17 vs 0%) in FG than ST, and lower (P < 0.05) peak
      blood lactate in FG than ST (7.2 +/- 0.9 vs 10.5 +/- 0.6 mmol/L). After the
      intervention period (IP), VO2 max (15%; P < 0.001), cycle time to exhaustion (7%;
      P < 0.05), and Yo-Yo Intermittent Endurance Level 1 performance (43%; P < 0.01)
      were improved in FG, but unchanged in ST and CO. HR during walking was 12% and
      10% lower (P < 0.05) in FG and ST, respectively, after IP. After IP, HR and blood
      lactate during jogging were 7% (P < 0.05) and 30% lower (P < 0.001) in FG, but
      unchanged in ST and CO. Sit-to-stand performance was improved (P < 0.01) by 29%
      in FG and 26% in ST, but not in CO. In conclusion, football and strength training
      for old men improves functional ability and physiological response to submaximal
      exercise, while football additionally elevates maximal aerobic fitness and
      exhaustive exercise performance.

PMID- 24903325
TI  - Phosphorylation of PAX3 contributes to melanoma phenotypes by affecting
      proliferation, invasion, and transformation.

PMID- 24903324
TI  - Effects of long-term developmental patterns of adiposity on levels of C-reactive
      protein and fibrinogen among North-American men and women: the Spokane Heart
      Study.
AB  - This study examined the heterogeneity in BMI development by identifying distinct
      developmental trajectories. These trajectories were further investigated by
      relating them to markers of low-grade inflammation later in life. Data from
      approximately 400 healthy volunteers participating in the Spokane Heart Study
      were collected in 2-year intervals, and four waves of data were available for the
      current analyses. Body weight was measured by BMI and low-grade inflammation by
      high-sensitivity C-reactive protein (CRP) and fibrinogen. Up to date statistical
      techniques, i.e., latent class growth models, were used to analyse heterogeneity
      in body weight, and linear regressions were run to analyse possible associations
      between trajectories of body weight and CRP/fibrinogen levels. Six trajectories
      were identified (three stable, two increasing, and one decreasing) which differed
      significantly on CRP/fibrinogen levels, highlighting the importance of weight
      trajectories. The differences were only partly explained by variations in
      lifestyle habits.

PMID- 24903327
TI  - Effects of modifying alternative respiration on nitric oxide-induced virus
      resistance and PR1 protein accumulation.
AB  - Nitric oxide (NO) is an important defensive signal in plants but its effects on
      virus infection are not well understood. Administration of NO-releasing compounds
      immediately before inoculation of tobacco leaves with potato virus X and tobacco
      mosaic virus decreased the accumulation of virus, indicating that NO can induce
      resistance rapidly. Resistance induction was inhibited by co-administration with
      an NO-scavenging compound or when experiments were done in transgenic tobacco
      plants expressing increased alternative respiratory pathway capacity due to
      constitutive expression of the plant mitochondrial enzyme, alternative oxidase
      (AOX). These results indicate that NO, which inhibits electron transport chain
      activity, is triggering defensive signalling by inducing changes in mitochondrial
      reactive oxygen species levels that are in turn regulated by AOX. Experiments
      using nahG-transgenic plants, which cannot accumulate the defensive plant hormone
      salicylic acid (SA) showed that NO rapidly induces resistance to virus infection
      independently of SA. However, this initial state of resistance may be transient.
      Subsequently, by 5 days post-treatment, NO had caused an increase in pathogenesis
      related protein 1 (PR1) expression (a proxy for increased SA biosynthesis), which
      correlated with a longer-term state of resistance to virus infection. The
      induction by NO of PR1 accumulation was modified in AOX-transgenic plants. This
      indicates that the influence of NO on defensive gene expression is in part
      mediated through its effects on mitochondria. 

PMID- 24903326
TI  - Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain
      injury.
AB  - Traumatic brain injury (TBI) induces severe harm and disability in many accident
      victims and combat-related activities. The heat-shock proteins Hsp70/Hsp110
      protect cells against death and ischemic damage. In this study, we used mice
      deficient in Hsp110 or Hsp70 to examine their potential requirement following
      TBI. Data indicate that loss of Hsp110 or Hsp70 increases brain injury and death
      of neurons. One of the mechanisms underlying the increased cell death observed in
      the absence of Hsp110 and Hsp70 following TBI is the increased expression of
      reactive oxygen species-induced p53 target genes Pig1, Pig8, and Pig12. To
      examine whether drugs that increase the levels of Hsp70/Hsp110 can protect cells
      against TBI, we subjected mice to TBI and administered Celastrol or BGP-15. In
      contrast to Hsp110- or Hsp70i-deficient mice that were not protected following
      TBI and Celastrol treatment, there was a significant improvement of wild-type
      mice following administration of these drugs during the first week following TBI.
      In addition, assessment of neurological injury shows significant improvement in
      contextual and cued fear conditioning tests and beam balance in wild-type mice
      that were treated with Celastrol or BGP-15 following TBI compared to TBI-treated
      mice. These studies indicate a significant role of Hsp70/Hsp110 in neuronal
      survival following TBI and the beneficial effects of Hsp70/Hsp110 inducers toward
      reducing the pathological consequences of TBI. Our data indicate that loss of
      Hsp110 or Hsp70 in mice increases brain injury following TBI. (a) One of the
      mechanisms underlying the increased cell death observed in the absence of these
      Hsps following TBI is the increased expression of ROS-induced p53 target genes
      known as Pigs. In addition, (b) using drugs (Celastrol or BGP-15) to increase
      Hsp70/Hsp110 levels protect cells against TBI, suggesting the beneficial effects
      of Hsp70/Hsp110 inducers to reduce the pathological consequences of TBI. 

PMID- 24903328
TI  - Prototype endogenous avian retroviruses of the genus Gallus.
AB  - Ancient endogenous retroviruses (ERVs), designated endogenous avian retrovirus
      (EAVs), are present in all Gallus spp. including the chicken, and resemble the
      modern avian sarcoma and leukosis viruses (ASLVs). The EAVs comprise several
      distinct retroviruses, including EAV-0, EAV-E51 and EAV-HP, as well as a putative
      member previously named the avian retrotransposon of chickens (ART-CH). Thus far,
      only the EAV-HP elements have been well characterized. Here, we determined
      sequences of representative EAV-0 and EAV-E51 proviruses by cloning and data
      mining of the 2011 assembly of the Gallus gallus genome. Although the EAV-0
      elements are primarily deleted in the env region, we identified two complete EAV
      0 env genes within the G. gallus genome and prototype elements sharing identity
      with an EAV-E51-related clone previously designated EAV-E33. Prototype EAV-0, EAV
      E51 and EAV-E33 gag, pol and env gene sequences used for phylogenetic analysis of
      deduced proteins showed that the EAVs formed three distinct clades, with EAV-0
      sharing the last common ancestor with the ASLVs. The EAV-E51 clade showed the
      greatest level of divergence compared with other EAVs or ASLVs, suggesting that
      these ERVs represented exogenous retroviruses that evolved and integrated into
      the germline over a long period of time. Moreover, the degree of divergence
      between the chicken and red jungle fowl EAV-E51 sequences suggested that they
      were more ancient than the other EAVs and may have diverged through mutations
      that accumulated post-integration. Finally, we showed that the ART-CH elements
      were chimeric defective ERVs comprising portions of EAV-E51 and EAV-HP rather
      than authentic retrotransposons.

PMID- 24903329
TI  - Antibody detection in tear samples as a surrogate to monitor host immunity
      against papillomavirus infections in vaccinated and naturally infected hosts.
AB  - Monitoring serum antibodies against natural infections or after immunizations has
      been a standard clinical diagnostic procedure. However, collecting blood samples
      requires trained personnel, and may cause discomfort and increase the risk of
      complications. In this study, we investigated whether tear samples could serve as
      a surrogate for serum samples to measure specific antibodies. A widely used
      preclinical cottontail rabbit papillomavirus (CRPV)/rabbit model has been a
      surrogate model for high-risk human papillomavirus (HPV) infections. New Zealand
      white rabbits, either naturally infected with CRPV or immunized with two
      clinically available HPV vaccines (Gardasil and Cervarix), were examined for
      antibody generation in both tear and serum samples. We demonstrated that
      antibodies were detectable in tears from both naturally infected as well as
      vaccinated animals. Overall, the antibody levels in tears were ~10-fold lower
      than those from the corresponding serum samples, but background noise was lower
      in tear samples. The isotypes of antibodies in tears were predominantly IgA and
      IgG. These findings showed clearly that tears could be a surrogate for serum
      samples for monitoring antibody responses. As collecting tears causes no
      discomfort and poses no risk to patients, it represents a novel and promising
      method for monitoring future HPV epidemiological studies as well as for use in
      clinical practice.

PMID- 24903330
TI  - Levels of maternal serum angiogenic factors in third-trimester normal
      pregnancies: reference ranges, influence of maternal and pregnancy factors and
      fetoplacental Doppler indices.
AB  - AIM: To establish normal ranges of maternal placental growth factor (PlGF),
      soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PlGF ratio at 32-41 weeks'
      gestation and to evaluate the influence of maternal characteristics, and of
      fetoplacental Doppler. MATERIAL AND METHODS: Serum levels of PlGF, sFlt-1 and
      sFlt-1/PlGF ratio were measured in 300 noncomplicated pregnancies (30 at each
      gestational week between 32 and 41). Quantile regression analysis was used to
      derive gestational age (GA)-adjusted normal ranges, and to account for
      characteristics that might influence serum levels. The relationship with Doppler
      indices was tested, including umbilical artery pulsatility index and middle
      cerebral artery pulsatility index. RESULTS: PlGF decreased with GA from 32 weeks,
      while sFlt-1 and sFlt-1/PlGF ratio increased steadily. None of the factors
      evaluated showed any significant influence on the levels of angiogenic factors.
      PlGF multiple of the median significantly correlated with mean uterine artery
      Doppler (R -0.17; p = 0.029). CONCLUSIONS: In normal pregnancies during the third
      trimester, serum PlGF decreases, sFlt-1 increases and sFlt-1/PlGF ratio increases
      with GA. Angiogenic factor levels needed no adjustment for factors such as
      smoking, body mass index, blood pressure or parity.

PMID- 24903331
TI  - Complicated and uncomplicated peptic ulcer disease: altered symptom response to a
      nutrient challenge linked to gastric motor dysfunction.
AB  - BACKGROUND: Bleeding peptic ulcer (BPU) frequently occurs in the absence of
      preceding dyspeptic symptoms. We have observed that patients with BPU had a
      diminished symptom response to nutrient challenge test compared to uncomplicated
      peptic ulcer disease (uPUD). We postulated that more symptoms are manifest in
      patients with uPUD than BPU because there are greater derangements in gastric
      motor function. AIM: To assess gastric emptying in patients with BPU, uPUD and
      healthy controls (HC). METHODS: We studied 17 patients with BPU, 10 with uPUD,
      and 15 HC. After an 8-hour fast, subjects ingested 200 ml of an enteral feeding
      solution, containing 5 MBq (99m)Tc-rhenium sulphide colloid, every 5 min up to a
      cumulative volume of 800 ml. Gastric emptying was measured by scintigraphy for
      the total, proximal and distal stomach. RESULTS: Patients with uPUD had
      significantly higher gastric retention in the proximal and total stomach at 100
      min than HC and BPU, while BPU had similar percent retention to HC. Patients with
      uPUD had significantly higher cumulative symptom response to the nutrient
      challenge than did HC and BPU, while BPU had similar symptom responses to HC.
      CONCLUSIONS: Patients with uPUD have significantly delayed gastric emptying
      compared to HC and BPU. Data suggest that in addition to alterations of visceral
      sensory function, altered gastric motor function occurs during a nutrient
      challenge in uPUD but not BPU. Gastric motor function may contribute to the
      manifestation of dyspeptic symptoms in PUD.

PMID- 24903333
TI  - Anticaries effect of an antioxidant-rich apple concentrate on enamel in an
      experimental biofilm-demineralization model.
AB  - AIMS: To assess the anticaries activity of an antioxidant-rich apple concentrate
      (ARAC) in an experimental biofilm caries model on enamel. METHODS AND RESULTS: A
      validated caries model with Streptococcus mutans UA159 biofilms was used.
      Biofilms were formed on enamel slabs during 5 days. To mimic cariogenic
      challenges, triplicate slabs were exposed three times per day for 5 min to 10%
      sucrose followed by five additional minutes of exposure to serial dilutions of
      ARAC in 0.9% NaCl. A triplicate slab exposed to 10% sucrose followed by 0.9% NaCl
      served as caries-positive control. Acidogenicity was estimated by medium pH twice
      per day. After the experimental phase, biofilms were recovered to determine
      biomass, viable bacteria and intra- and extracellular polysaccharides. Slabs were
      used to estimate demineralization by the percentage of surface microhardness loss
      (%SHL). Differences among treatments were analysed by anova and Bonferroni test
      (P < 0.05). Streptococcus mutans biofilms were exposed to ARAC after a cariogenic
      challenge with sucrose-induced lower enamel demineralization than the positive
      control. The highest dilution of ARAC at 1 : 100 000 (v/v) showed the most marked
      reduction in demineralization of about 57%. Although no differences were observed
      in the number of bacterial cells, the intracellular polysaccharides or in the
      biomass (P > 0.05), the highest dilution of the apple concentrate induced
      significantly lower extracellular polysaccharide formation by the biofilm.
      CONCLUSIONS: An apple concentrate in low concentrations appears to have a
      potential anticaries activity on enamel. Data suggest a metabolic rather than an
      antimicrobial mechanism, but further research is needed. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Phenolic compounds contained in apple concentrates seem to have
      anticaries properties that may be effective even in the presence of sucrose and
      in very low doses. Nutritional interventions that do not require rescinding from
      sucrose might be derived from these findings.

PMID- 24903332
TI  - The role of law and governance reform in the global response to non-communicable
      diseases.
AB  - Addressing non-communicable diseases ("NCDs") and their risk-factors is one of
      the most powerful ways of improving longevity and healthy life expectancy for the
      foreseeable future - especially in low- and middle-income countries. This paper
      reviews the role of law and governance reform in that process. We highlight the
      need for a comprehensive approach that is grounded in the right to health and
      addresses three aspects: preventing NCDs and their risk factors, improving access
      to NCD treatments, and addressing the social impacts of illness. We highlight
      some of the major impediments to the passage and implementation of laws for the
      prevention and control of NCDs, and identify important practical steps that
      governments can take as they consider legal and governance reforms at country
      level.We review the emerging global architecture for NCDs, and emphasise the need
      for governance structures to harness the energy of civil society organisations
      and to create a global movement that influences the policy agenda at the country
      level. We also argue that the global monitoring framework would be more effective
      if it included key legal and policy indicators. The paper identifies priorities
      for technical legal assistance in implementing the WHO Global Action Plan for the
      Prevention and Control of NCDs 2013-2020. These include high-quality legal
      resources to assist countries to evaluate reform options, investment in legal
      capacity building, and global leadership to respond to the likely increase in
      requests by countries for technical legal assistance. We urge development
      agencies and other funders to recognise the need for development assistance in
      these areas. Throughout the paper, we point to global experience in dealing with
      HIV and draw out some relevant lessons for NCDs. 

PMID- 24903334
TI  - The causes and molecular consequences of polyploidy in flowering plants.
AB  - Polyploidy is an important force shaping plant genomes. All flowering plants are
      descendants of an ancestral polyploid species, and up to 70% of extant vascular
      plant species are believed to be recent polyploids. Over the past century, a
      significant body of knowledge has accumulated regarding the prevalence and
      ecology of polyploid plants. In this review, we summarize our current
      understanding of the causes and molecular consequences of polyploidization in
      angiosperms. We also provide a discussion on the relationships between polyploidy
      and adaptation and suggest areas where further research may provide a better
      understanding of polyploidy. 

PMID- 24903335
TI  - Calcium signalling in pericytes.
AB  - Recent advances in pericyte research have contributed to our understanding of the
      physiology and pathophysiology of microvessels. The microvasculature consists of
      arteriolar and venular networks located upstream and downstream of the
      capillaries. Arterioles are surrounded by a monolayer of spindle-shaped myocytes,
      while terminal branches of precapillary arterioles, capillaries and all sections
      of postcapillary venules are encircled by a monolayer of morphologically diverse
      pericytes. There are physiological differences in the response of pericytes and
      myocytes to vasoactive molecules, suggesting that these two vascular cell types
      could have different functional roles in the regulation of local blood flow. The
      contractile activity of pericytes and myocytes is controlled by changes of
      cytosolic free Ca(2+) concentration. In this short review, we summarize our
      results and those of other authors on the contractility of pericytes and their
      Ca(2+) signalling. We describe results regarding sources of Ca(2+) and mechanisms
      of Ca(2+) release and Ca(2+) entry in control of the spatiotemporal
      characteristics of the Ca(2+) signals in pericytes.

PMID- 24903336
TI  - Li2ZnV3O8: a vanadium-based geometrically frustrated spinel system.
AB  - We report the synthesis and characterization of Li2ZnV3O8, which is a new Zn
      doped LiV2O4 system containing only tetravalent vanadium. A Curie-Weiss
      susceptibility with a Curie-Weiss temperature of thetaCW ~ -214 K suggests the
      presence of strong antiferromagnetic correlations in this system. We have
      observed a splitting between the zero-field cooled (ZFC) and field cooled (FC)
      susceptibility curves below 6 K. A peak is present in the ZFC curve around 3.5 K,
      suggestive of spin-freezing. Similarly, a broad hump is also seen in the inferred
      magnetic heat capacity around 9 K. The consequent entropy change is only about 8%
      of the value expected for an ordered S = 1/2 system. This reduction indicates the
      continued presence of large disorder in the system in spite of the large thetaCW,
      which might result from strong geometric frustration in the system. We did not
      find any temperature T dependence in our (7)Li nuclear magnetic resonance shift
      down to 6 K (an abrupt change in the shift does take place below 6 K), though
      considerable T-dependence has been found in the literature for LiV2O4--undoped or
      with other Zn/Ti contents. Consistent with the above observation, the (7)Li
      nuclear spin-lattice relaxation rate 1/T1 is relatively small and nearly T
      independent, except for a small increase close to the freezing temperature which,
      once again, is small compared to undoped or 10% Zn or 20% Ti-doped LiV2O4.

PMID- 24903337
TI  - Insight: implantable medical devices.
AB  - Implantable electronic medical devices have achieved remarkable medical advances
      in the treatment of the most challenging conditions, starting with the
      introduction of the first implantable pacemaker in 1958. Increasing demand for
      innovation in existing and novel implantable devices is fuelled by the growing
      aging population and the increased prevalence of chronic diseases. This
      perspective article provides an overview of the implantable medical device
      ecosystem, highlights recent developments, and discusses challenges and
      opportunities for translation of new innovative implants enabled by
      microtechnologies and microfabrication. 

PMID- 24903338
TI  - SUMOylation of the ING1b tumor suppressor regulates gene transcription.
AB  - The INhibitor of Growth (ING) proteins are encoded as multiple isoforms in five
      ING genes (ING1 -5) and act as type II tumor suppressors. They are growth
      inhibitory when overexpressed and are frequently mislocalized or downregulated in
      several forms of cancer. ING1 and ING2 are stoichiometric members of histone
      deacetylase complexes, whereas ING3-5 are stoichiometric components of different
      histone acetyltransferase complexes. The INGs target these complexes to histone
      marks, thus acting as epigenetic regulators. ING proteins affect angiogenesis,
      apoptosis, DNA repair, metastasis and senescence, but how the proteins themselves
      are regulated is not yet clear. Here, we find a small ubiquitin-like modification
      (SUMOylation) of the ING1b protein and identify lysine 193 (K193) as the
      preferred ING1b SUMO acceptor site. We also show that PIAS4 is the E3 SUMO ligase
      responsible for ING1b SUMOylation on K193. Sequence alignment reveals that the
      SUMO consensus site on ING1b contains a phosphorylation-dependent SUMOylation
      motif (PDSM) and our data indicate that the SUMOylation on K193 is enhanced by
      the S199D phosphomimic mutant. Using an ING1b protein mutated at the major
      SUMOylation site (ING1b E195A), we further demonstrate that ING1b SUMOylation
      regulates the binding of ING1b to the ISG15 and DGCR8 promoters, consequently
      regulating ISG15 and DGCR8 transcription. These results suggest a role for ING1b
      SUMOylation in the regulation of gene transcription. 

PMID- 24903339
TI  - Lung adenocarcinoma subtypes definable by lung development-related miRNA
      expression profiles in association with clinicopathologic features.
AB  - Accumulation of genetic and epigenetic changes alters regulation of a web of
      interconnected genes including microRNAs (miRNAs), which confer hallmark
      capabilities and characteristic cancer features. In this study, the miRNA and
      messenger RNA expression profiles of 126 non-small cell lung cancer specimens
      were analyzed, with special attention given to the diversity of lung
      adenocarcinomas. Of those, 76 adenocarcinomas were classified into two major
      subtypes, developing lung-like and adult lung-like, based on their distinctive
      miRNA expression profiles resembling those of either developing or adult lungs,
      respectively. A systems biology-based approach using a Bayesian network and non
      parametric regression was employed to estimate the gene regulatory circuitry
      functioning in patient tumors in order to identify subnetworks enriched for genes
      with differential expression between the two major subtypes. miR-30d and miR-195,
      identified as hub genes in such subnetworks, had lower levels of expression in
      the developing lung-like subtype, whereas introduction of miR-30d or miR-195 into
      the lung cancer cell lines evoked shifts of messenger RNA expression profiles
      toward the adult lung-like subtype. Conversely, the influence of miR-30d and miR
      195 was significantly different between the developing lung-like and adult lung
      like subtypes in our analysis of the patient data set. In addition, RRM2, a child
      gene of the miR-30d-centered subnetwork, was found to be a direct target of miR
      30d. Together, our findings reveal the existence of two miRNA expression profile
      defined lung adenocarcinoma subtypes with distinctive clinicopathologic features
      and also suggest the usefulness of a systems biology-based approach to gain
      insight into the altered regulatory circuitry involved in cancer development. 

PMID- 24903340
TI  - Three-dimensional cancer models mimic cell-matrix interactions in the tumour
      microenvironment.
AB  - Basic in vitro systems can be used to model and assess complex diseases, such as
      cancer. Recent advances in this field include the incorporation of multiple cell
      types and extracellular matrix proteins into three-dimensional (3D) models to
      recapitulate the structure, organization and functionality of live tissue in
      situ. Cells within such a 3D environment behave very differently from cells on
      two-dimensional (2D) substrates, as cell-matrix interactions trigger signalling
      pathways and cellular responses in 3D, which may not be observed in 2D. Thus, the
      use of 3D systems can be advantageous for the assessment of disease progression
      over 2D set-ups alone. Here, we highlight the current advantages and challenges
      of employing 3D systems in the study of cancer and provide an overview to guide
      the appropriate use of distinct models in cancer research. 

PMID- 24903341
TI  - Fluoroacetate biosynthesis from the marine-derived bacterium Streptomyces
      xinghaiensis NRRL B-24674.
AB  - Genome sequencing identified a fluorinase gene in the marine bacterium
      Streptomyces xinghaiensis NRRL B-24674. Fermentation of the organism with
      inorganic fluoride (2 mM) demonstrated that the organism could biosynthesise
      fluoroacetate and that fluoroacetate production is sea-salt dependent. This is
      the first fluorometabolite producing microorganism identified from the marine
      environment. 

PMID- 24903342
TI  - Propargylamine-isothiocyanate reaction: efficient conjugation chemistry in
      aqueous media.
AB  - A coupling reaction between secondary propargyl amines and isothiocyanates in
      aqueous media is described. The reaction is high-yielding and affords cyclized
      products within 2-24 h. A functionalized ether lipid was synthesized in 8 steps,
      formulated as liposomes with POPC and conjugated to FITC under mild conditions
      using this method. 

PMID- 24903343
TI  - Progression of diffuse myocardial fibrosis assessed by cardiac magnetic resonance
      T1 mapping.
AB  - To evaluate long-term changes in diffuse myocardial fibrosis using cardiac
      magnetic resonance (CMR) with late gadolinium enhancement (LGE) and T1 mapping.
      Patients with chronic stable cardiomyopathy and stable clinical status (n = 52)
      underwent repeat CMR at a 6 month or greater follow up interval and had LGE and
      left ventricular (LV) T1 mapping CMR. Diffuse myocardial fibrosis (excluding
      areas of focal myocardial scar) was assessed by post gadolinium myocardial T1
      times. Mean baseline age of 52 patients (66 % male) was 35 +/- 19 years with a
      mean interval between CMR examinations of 2.0 +/- 0.8 years. CMR parameters,
      including LV mass and ejection fraction, showed no change at follow-up CMR (p >
      0.05). LVT1 times (excluding focal scar) decreased over the study interval (from
      468 +/- 106 to 434 +/- 82 ms, p = 0.049). 38 Patients had no visual LGE-, while
      14 were LGE+. For LGE- patients, greater change in LV mass and end systolic
      volume index were associated with change in T1 time (beta = -2.03 ms/g/m(2), p =
      0.035 and beta = 2.1 ms/mL/m(2), p = 0.029, respectively). For LGE+ patients,
      scar size was stable between CMR1 and CMR2 (10.7 +/- 13.8 and 11.5 +/- 13.9 g,
      respectively, p = 0.32). These results suggest that diffuse myocardial fibrosis,
      as assessed by T1 mapping, progresses over time in patients with chronic stable
      cardiomyopathy.

PMID- 24903344
TI  - Reply: 'a review of central retinal artery occlusion: clinical presentation and
      management'.

PMID- 24903345
TI  - Medical therapy for uveal effusion syndrome.
AB  - PURPOSE: To report a case series of three patients with bilateral uveal effusion
      syndrome (UES), treated conservatively with oral carbonic anhydrase inhibitors
      and topical prostaglandin analogues (PAs). METHODS: Three patients with bilateral
      UES were treated with the same initial therapy. Topical PA latanoprost 0.005% and
      acetazolamide 250 mg were administered in order to reduce intraocular pressure,
      improve uveoscleral outflow, and facilitate resolution of uveal effusion.
      RESULTS: The chorioretinal detachment resolved within 3 months in two reported
      patients while the third one underwent surgery on his left eye. After clinical
      improvement, further oral therapy with acetazolamide was stopped, while topical
      prostaglandins were continued for at least the next 3 months. All patients were
      free from recurrence during the follow-up period. CONCLUSION: Although the
      usually recommended UES therapy is partial or full-thickness sclerectomy, our
      case series showed apparent resolution of chorioretinal detachment in two
      patients on medical therapy alone. Conservative therapy may be the first step
      before the standard recommended surgical approach, but further studies are needed
      to verify the effectiveness of reported therapy.

PMID- 24903346
TI  - Concerning central retinal artery occlusion (CRAO) and cerebral stroke.

PMID- 24903347
TI  - Impact of dutasteride on nocturia in men with lower urinary tract symptoms
      suggestive of benign prostatic hyperplasia (LUTS/BPH): a pooled analysis of three
      phase III studies.
AB  - PURPOSE: To assess the impact of dutasteride compared with placebo on nocturia in
      men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia,
      using pooled data from dutasteride phase III studies. METHODS: Nocturia was
      assessed using Question 7 of the International Prostate Symptom Score
      questionnaire. Efficacy measures included: mean change in nocturia at 24 months;
      proportion of patients with improvement/worsening in nocturia; nocturnal voiding
      frequency at baseline and study end, overall and by baseline subgroups; and
      nocturnal voiding frequency <2 at study end in patients with baseline score >= 2.
      RESULTS: In total, 4,321 patients with a mean age of 66 years were evaluated.
      From month 12 onwards, mean nocturia improvements were significantly superior
      with dutasteride than with placebo (p <= 0.05). Reduction in nocturia was
      significantly better with dutasteride than with placebo across all baseline
      subgroups tested (p <= 0.05). Also at month 24, dutasteride therapy resulted in a
      greater proportion of subjects with nocturia improvement compared with placebo (p
      <= 0.05), with the largest treatment group differences in subjects with a
      baseline nocturia score of 2 or 3. Among patients with significant nocturia at
      baseline (score >= 2), significantly more subjects with dutasteride versus
      placebo had a score <2 at month 24 (26 vs. 19 %, p < 0.001). CONCLUSIONS: After
      24 months of treatment, dutasteride treatment provided significantly greater
      improvements in nocturia, and less worsening, compared with placebo, primarily in
      subjects with two or three nocturia episodes per night. Studies specifically
      designed to assess nocturia are required to prospectively confirm these findings.

PMID- 24903348
TI  - Retroperitoneal laparoscopic renal tumour enucleation with local hypotension on
      demand.
AB  - PURPOSE: Laparoscopic partial nephrectomy is the standard treatment for
      peripheric cT1 renal tumours and is usually performed under warm ischaemia.
      However, it is important to reduce ischaemia time as much as possible to avoid
      renal damage. The aim of our study was to investigate the feasibility and safety
      of our technique and to evaluate short-term functional and oncological results.
      MATERIALS AND METHODS: From June 2010 to December 2012, 54 consecutive patients
      with T1a-T1b renal tumour were enrolled in a high-volume tertiary institution.
      All patients underwent laparoscopic enucleation with controlled selective
      hypotension on demand. Karnofsky performance status scale, R.E.N.A.L. Nephrometry
      Score and Clavien-Dindo Classification were used to assess patients' status, to
      stratify patients according to kidney disease and to evaluate complications,
      respectively. Renal function was evaluated with serum creatinine (sCr) and
      estimated glomerular filtration rate (eGFR) preoperative and 3, 5, 7 and 90 days
      postoperatively. RESULTS: All the procedures were completed laparoscopically.
      Renal hypotension was necessary in 3/54 cases. Mean intraoperatively blood loss
      was 210 +/- 98 ml. Renal carcinoma was found in 87 % patients. Margins revealed
      to be positive in 5.5 % cases. Mean hospital stay was 7.2 days. Grade IIIa and
      IIIb postoperative complications were 5.5 and 11 %, respectively. At 3 months,
      increase for sCr was 0.04 mg/dL; eGFR reduction was 1.2 ml/min. At a median
      follow-up of 20 months, there was one local recurrence that happened in a
      positive margin case. CONCLUSIONS: Our preliminary results proved laparoscopic
      enucleation with controlled selective local hypotension on demand to be a
      feasible, safe and effective technique for T1 renal tumours.

PMID- 24903349
TI  - Is there a peripheral site of action contributing to the voiding effects of
      alpha2-adrenoceptor agonists and antagonists?
AB  - PURPOSE: Since it has not been established whether there is an effect on voiding
      exerted by direct stimulation or blockade of alpha2-adrenoceptors in the bladder
      and urethra, MK-467, a peripherally acting alpha2-adrenoceptor antagonist not
      penetrating into the CNS, was used to test whether part of the voiding effects of
      systemically given alpha2-adrenoceptor agonists is peripheral. METHODS:
      Urodynamic recordings from 27 conscious male adult C57/Bl J-strain mice were
      performed. After vehicle (saline) administration, two groups of animals were
      treated first with the selective alpha2-adrenoceptor agonist dexmedetomidine
      (Dex) and then with the selective alpha2-adrenoceptor antagonists atipamezole
      (Ati) or MK-467. Two other groups were first treated with Ati or MK-467 and then
      with Dex. RESULTS: Treatment with vehicle or alpha2-adrenoceptor antagonists
      alone did not affect micturition parameters. All animals treated first with Dex
      developed overflow incontinence. Treatment with Ati after Dex reversed almost
      totally the effects of Dex on all voiding parameters, but treatment with MK-467
      after Dex showed no detectable improvement. Treatment with Dex after Ati had no
      effect on any voiding parameter except maximal pressure. When mice were treated
      with Dex after MK-467, overflow incontinence was produced in seven of eight
      animals studied. CONCLUSIONS: The absence of functionally relevant peripheral
      effects on voiding mediated via alpha2-adrenoceptors is supported by the finding
      that neither Ati nor MK-467 alone had any effect on micturition parameters and by
      the inability of MK-467 to inhibit the effects of Dex, suggesting that the
      relevant Dex effects were exerted within the CNS.

PMID- 24903350
TI  - Fingerprinting breast cancer vs. normal mammary cells by mass spectrometric
      analysis of volatiles.
AB  - There is increasing interest in the development of noninvasive diagnostic methods
      for early cancer detection, to improve the survival rate and quality of life of
      cancer patients. Identification of volatile metabolic compounds may provide an
      approach for noninvasive early diagnosis of malignant diseases. Here we analyzed
      the volatile metabolic signature of human breast cancer cell lines versus normal
      human mammary cells. Volatile compounds in the headspace of conditioned culture
      medium were directly fingerprinted by secondary electrospray ionization-mass
      spectrometry. The mass spectra were subsequently treated statistically to
      identify discriminating features between normal vs. cancerous cell types. We were
      able to classify different samples by using feature selection followed by
      principal component analysis (PCA). Additionally, high-resolution mass
      spectrometry allowed us to propose their chemical structures for some of the most
      discriminating molecules. We conclude that cancerous cells can release a
      characteristic odor whose constituents may be used as disease markers. 

PMID- 24903351
TI  - Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine
      enantiomers.
AB  - PURPOSE: We examined the effect of a single apple juice intake on the
      pharmacokinetics of fexofenadine enantiomers in healthy Japanese subjects.
      METHODS: In a randomized two phase, open-label crossover study, 14 subjects
      received 60 mg of racemic fexofenadine simultaneously with water or apple juice.
      For the uptake studies, oocytes expressing organic anion-transporting polypeptide
      2B1 (OATP2B1) were incubated with 100 MUM (R)- and (S)-fexofenadine in the
      presence or absence of 10 % apple juice. RESULTS: One-time ingestion of apple
      juice significantly decreased the area under the plasma concentration-time curve
      (AUC0-24) for (R)- and (S)-fexofenadine by 49 and 59 %, respectively, and
      prolonged the time to reach the maximum plasma concentration (t max) of both
      enantiomers (P < 0.001). Although apple juice greatly reduced the amount of (R)-
      and (S)-fexofenadine excretion into urine (Ae0-24) by 54 and 58 %, respectively,
      the renal clearances of both enantiomers were unchanged between the control and
      apple juice phases. For in vitro uptake studies, the uptake of both fexofenadine
      enantiomers into OATP2B1 complementary RNA (cRNA)-injected oocytes was
      significantly higher than that into water-injected oocytes, and this effect was
      greater for (R)-fexofenadine. In addition, apple juice significantly decreased
      the uptake of both enantiomers into OATP2B1 cRNA-injected oocytes. CONCLUSIONS:
      These results suggest that OATP2B1 plays an important role in the stereoselective
      pharmacokinetics of fexofenadine and that one-time apple juice ingestion probably
      inhibits intestinal OATP2B1-mediated transport of both enantiomers. In addition,
      this study demonstrates that the OATP2B1 inhibition effect does not require
      repeated ingestion or a large volume of apple juice.

PMID- 24903352
TI  - Botulinum toxin A's expanding role in the management of pediatric lower urinary
      tract dysfunction.
AB  - Botulinum toxin A's (Onabotulinum toxin A - OnabotA) utility in the pediatric
      population is evolving, and is currently being used in the treatment of lower
      urinary tract dysfunction, both in children with neuropathic compromise, and non
      neuropathic overactive bladders. The results of having OnabotA injected directly
      into the bladder wall cystoscopically are: a more compliant bladder with reduced
      bladder pressure, avoiding renal compromise and upper urinary tract
      deterioration; increased bladder capacity; and the ability for children to reach
      an improved degree of urinary continence through a minimally invasive approach. A
      growing body of research in patients with either neuropathic bladders or
      overactive bladders (OAB), have shown excellent results when looking at
      urodynamic parameters, patient satisfaction and improvement in symptomatology.
      One of the main indications for the use of OnabotA in children with neuropathic
      bladders is to delay or avoid the need for augmentation cystoplasty. By achieving
      the aforementioned results, some children can delay or avoid this more invasive
      and permanent procedure. Prospective studies are needed to answer questions
      regarding optimal dosage and frequency, ideal patient selection criteria and
      assessment of long-term outcomes and complications.

PMID- 24903353
TI  - Alteration of tear mucin 5AC in office workers using visual display terminals:
      The Osaka Study.
AB  - IMPORTANCE: There are limited reports on the relationship between mucin 5AC
      (MUC5AC) concentrations in tears, working hours, and the frequency of ocular
      symptoms in visual display terminal (VDT) users. This investigation evaluated
      these relationships among patients with dry eye disease (DED) and individuals
      serving as controls. OBJECTIVE: To determine the relationship between MUC5AC
      concentration in the tears of VDT users based on the diagnosis of DED and
      frequency of ocular symptoms. DESIGN, SETTING, AND PARTICIPANTS: An
      institutional, cross-sectional study was conducted. Participants included 96
      young and middle-aged Japanese office workers. Both eyes of 96 volunteers (60 men
      and 36 women) were studied. Participants working in a company that used VDTs
      completed questionnaires about their working hours and the frequency of ocular
      symptoms. Dry eye disease was diagnosed as definite or probable, or it was not
      present. Tear fluid was collected from the inferior fornix after instillation of
      50 MUL of sterilized saline. The MUC5AC concentration was normalized to tear
      protein content and expressed as MUC5AC (nanograms) per tear protein
      (milligrams). The differences in MUC5AC concentration between DED groups, between
      VDT working hours (short, intermediate, and long), and between symptomatic and
      asymptomatic groups were evaluated with 95% CIs based on nonparametric Hodges
      Lehmann determination. MAIN OUTCOMES AND MEASURES: Ocular surface evaluation,
      prevalence of DED, and MUC5AC concentration. RESULTS: The prevalence of definite
      and probable DED was 9% (n = 9) and 57% (n = 55), respectively. The mean MUC5AC
      concentration was lower in the tears of VDT users with definite DED than in those
      with no DED (P = .02; Hodges-Lehmann estimator, -2.17; 95% CI, -4.67 to -0.30).
      The mean MUC5AC concentration in tears was lower in the group that worked longer
      hours than in the group that worked shorter hours (P = .049; estimated
      difference, -1.65; 95% CI, -3.12 to 0.00). Furthermore, MUC5AC concentration was
      lower in participants with symptomatic eye strain than in asymptomatic
      individuals (P = .001; estimated difference, -1.71; 95% CI, -2.86 to -0.63).
      CONCLUSIONS AND RELEVANCE: The data obtained in the present study suggest that
      office workers with prolonged VDT use, as well as those with an increased
      frequency of eye strain, have a low MUC5AC concentration in their tears.
      Furthermore, MUC5AC concentration in the tears of patients with DED may be lower
      than that in individuals without DED.

PMID- 24903354
TI  - Immediate and 12 months follow up of function and lead integrity after cranial
      MRI in 356 patients with conventional cardiac pacemakers.
AB  - BACKGROUND: Conventional cardiac pacemakers are still often regarded as a
      contraindication to magnetic resonance imaging (MRI). We conducted this study to
      support the hypothesis that it is safe to scan patients with cardiac pacemakers
      in a 1.5 Tesla MRI, if close supervision and monitoring as well as adequate pre-
      and postscan programming is provided. METHODS: We followed up 356 patients (age
      61.3 +/- 9.1 yrs., 229 men) with single (n = 132) or dual chamber (n = 224)
      cardiac pacemakers and urgent indication for a cranial MRI for 12 months. The
      scans were performed at 1.5T. During the scan patients were monitored with a 3
      lead ECG and pulse oximetry. Prior to the scan pacemakers were programmed
      according to our own protocol. RESULTS: All 356 scans were completed without
      complications. No arrhythmias were induced, programmed parameters remained
      unchanged. No pacemaker dysfunction was identified. Follow-up examinations were
      performed immediately, 2 weeks, 2, 6, and 12 months after the scan. There was no
      significant change of pacing capture threshold (ventricular 0.9 +/- 0.4 V@0.4 ms,
      atrial 0.9 +/- 0.3 V@0.4 ms) immediately (ventricular 1.0 +/- 0.3 V@0.4 ms,
      atrial 0.9 +/- 0.4 V@0.4 ms) or at 12 months follow-up examinations (ventricular
      0.9 +/- 0.2 V@0.4 ms, atrial 0.9 +/- 0.3 V@0.4 ms). There was no significant
      change in sensing threshold (8.0 +/- 4.0 mV vs. 8.1 +/- 4.2 mV ventricular lead,
      2.0 +/- 0.9 mV vs. 2.1 +/- 1.0 mV atrial lead) or lead impedance (ventricular 584
      +/- 179 Omega vs. 578 +/- 188 Omega, atrial 534 +/- 176 Omega vs. 532 +/- 169
      Omega) after 12 months. CONCLUSIONS: This supports the evidence that patients
      with conventional pacemakers can safely undergo cranial MRI in a 1.5T system with
      suitable preparation, supervision and precautions. Long term follow-up did not
      reveal significant changes in pacing capture nor sensing threshold.

PMID- 24903356
TI  - Does the Continued Use of the MCAT Hinder Care for Minority Patients?

PMID- 24903355
TI  - Intention to Breastfeed as a Predictor of Initiation of Exclusive Breastfeeding
      in Hispanic Women.
AB  - Exclusive breastfeeding (EBF) is the most efficacious form of infant feeding and
      nutrition. Hispanic mothers in the US are more likely than mothers of other
      racial/ethnic groups to supplement with formula in the first 2 days of life. The
      purpose of this study was to explore infant feeding intentions during the
      prenatal period as a predictor of EBF at postpartum discharge in a sample of
      Hispanic women (n = 99). At discharge, 51 % of the women were EBF, 44 % were
      breastfeeding and supplementing with formula, and 5 % were feeding only formula.
      Intention to breastfeed was found to be a strong and potentially modifiable
      predictor of breastfeeding behavior, showing a significant association with EBF
      upon discharge from the hospital after birth when linked with acceptance of
      pregnancy and method of delivery. Prenatal care offers a unique opportunity to
      enhance intentions to breastfeed that may lead to improved EBF in this health
      vulnerable population. 

PMID- 24903357
TI  - Not all anthocyanins are born equal: distinct patterns induced by stress in
      Arabidopsis.
AB  - MAIN CONCLUSION: Different abiotic stress conditions induce distinct sets of
      anthocyanins, indicating that anthocyanins have different biological functions,
      or that decoration patterns of each anthocyanin are used for unique purposes
      during stress. The induction of anthocyanin accumulation in vegetative tissues is
      often considered to be a response of plants to biotic or abiotic stress
      conditions. Arabidopsis thaliana (Arabidopsis) accumulates over 20 anthocyanins
      derived from the anthocyanidin cyanidin in an organ-specific manner during
      development, but the anthocyanin chemical diversity for their alleged stress
      protective functions remains unclear. We show here that, when grown in various
      abiotic stress conditions, Arabidopsis not only often accumulates significantly
      higher levels of total anthocyanins, but different stress conditions also favor
      the accumulation of different sets of anthocyanins. For example, the anthocyanin
      patterns of seedlings grown at pH 3.3 or in media lacking phosphate are very
      similar and characterized by relatively high levels of the anthocyanins A8 and
      A11. In contrast, anthocyanin inductive conditions (AIC) provided by high sucrose
      media are characterized by high accumulation of A9* and A5 relative to other
      stress conditions. The modifications present in each condition correlate
      reasonably well with the induction of the respective anthocyanin modification
      enzymes. Taken together, our results suggest that Arabidopsis anthocyanin
      profiles provide 'fingerprints' that reflect the stress status of the plants.

PMID- 24903358
TI  - Photoprotection by foliar anthocyanins mitigates effects of boron toxicity in
      sweet basil (Ocimum basilicum).
AB  - Boron (B) toxicity is an important agricultural problem in arid environments.
      Excess edaphic B compromises photosynthetic efficiency, limits growth and reduces
      crop yield. However, some purple-leafed cultivars of sweet basil (Ocimum
      basilicum) exhibit greater tolerance to high B concentrations than do green
      leafed cultivars. We hypothesised that foliar anthocyanins protect basil leaf
      mesophyll from photo-oxidative stress when chloroplast function is compromised by
      B toxicity. Purple-leafed 'Red Rubin' and green-leafed 'Tigullio' cultivars,
      grown with high or negligible edaphic B, were given a photoinhibitory light
      treatment. Possible effects of photoabatement by anthocyanins were simulated by
      superimposing a purple polycarbonate filter on the green leaves. An ameliorative
      effect of light filtering on photosynthetic quantum yield and on photo-oxidative
      load was observed in B-stressed plants. In addition, when green protoplasts from
      both cultivars were treated with B and illuminated through a screen of
      anthocyanic protoplasts or a polycarbonate film which approximated cyanidin-3-O
      glucoside optical properties, the degree of photoinhibition, hydrogen peroxide
      production, and malondialdehyde content were reduced. The data provide evidence
      that anthocyanins exert a photoprotective role in purple-leafed basil mesophyll
      cells, thereby contributing to improved tolerance to high B concentrations. 

PMID- 24903360
TI  - Photosynthetic costs and benefits of abaxial versus adaxial anthocyanins in
      Colocasia esculenta 'Mojito'.
AB  - MAIN CONCLUSION: Anthocyanins in upper (adaxial) leaf tissues provide greater
      photoprotection than in lower (abaxial) tissues, but also predispose tissues to
      increased shade acclimation and, consequently, reduced photosynthetic capacity.
      Abaxial anthocyanins may be a compromise between these costs/benefits. Plants
      adapted to shaded understory environments often exhibit red/purple anthocyanin
      pigmentation in lower (abaxial) leaf surfaces, but rarely in upper (adaxial)
      surfaces. The functional significance of this color pattern in leaves is poorly
      understood. Here, we test the hypothesis that abaxial anthocyanins protect leaves
      of understory plants from photo-oxidative stress via light attenuation during
      periodic exposure to high incident sunlight in the forest understory, without
      interfering with sunlight capture and photosynthesis during shade conditions. We
      utilize a cultivar of Colocasia esculenta exhibiting adaxial and abaxial
      anthocyanin variegation within individual leaves to compare tissues with the
      following color patterns: green adaxial, green abaxial (GG), green adaxial, red
      abaxial (GR), red adaxial, green abaxial (RG), and red adaxial, red abaxial (RR).
      Consistent with a photoprotective function of anthocyanins, tissues exhibited
      symptoms of increasing photoinhibition in the order (from least to greatest): RR,
      RG, GR, GG. Anthocyanic tissues also showed symptoms of shade acclimation (higher
      total chl, lower chl a/b) in the same relative order. Inconsistent with our
      hypothesis, we did not observe any differences in photosynthetic CO2 uptake under
      shade conditions between the tissue types. However, GG and GR had significantly
      (39 %) higher photosynthesis at saturating irradiance (A sat) than RG and RR.
      Because tissue types did not differ in nitrogen content, these patterns likely
      reflect differences in resource allocation at the tissue level, with greater
      nitrogen allocated toward energy processing in GG and GR, and energy capture in
      RG and RR (consistent with relative sun/shade acclimation). We conclude that
      abaxial anthocyanins are likely advantageous in understory environments because
      they provide some photoprotection during high-light exposure, but without the
      cost of decreased A sat associated with adaxial anthocyanin-induced shade
      syndrome.

PMID- 24903359
TI  - Update on transparent testa mutants from Arabidopsis thaliana: characterisation
      of new alleles from an isogenic collection.
AB  - MAIN CONCLUSION: We present a comprehensive overview on flavonoid-related
      phenotypes of A. thaliana tt and tds mutants, provide tools for their
      characterisation, increase the number of available alleles and demonstrate that
      tds3 is allelic to tt12 and tds5 to aha10. Flavonoid biosynthesis is one of the
      best-studied secondary metabolite pathways in plants. In the model system
      Arabidopsis thaliana it leads to the synthesis of three phenolic compound
      classes: flavonol glycosides, anthocyanins and proanthocyanidins (PAs). PAs
      appear brown in their oxidised polymeric forms, and most A. thaliana mutants
      impaired in flavonoid accumulation were identified through screens for lack of
      this seed coat pigmentation. These mutants are referred to as transparent testa
      (tt) or tannin-deficient seed (tds). More than 20 mutants of these types have
      been published, probably representing most of the genes relevant for PA
      accumulation in A. thaliana. However, data about the genes involved in PA
      deposition or oxidation are still rather scarce. Also, for some of the known
      mutants it is unclear if they represent additional loci or if they are allelic to
      known genes. For the present study, we have performed a systematic phenotypic
      characterisation of almost all available tt and tds mutants and built a
      collection of mutants in the genetic background of the accession Columbia to
      minimise effects arising from ecotype variation. We have identified a novel tt6
      allele from a forward genetic screen and demonstrated that tds3 is allelic to
      tt12 and tds5 to aha10.

PMID- 24903361
TI  - Form and function in the digenea.

PMID- 24903362
TI  - The systematics of the trematoda.

PMID- 24903363
TI  - Schistosomiasis.

PMID- 24903364
TI  - Fascioliasis.

PMID- 24903365
TI  - Paragonimiasis.

PMID- 24903366
TI  - Liver flukes: Clonorchis and Opisthorchis.

PMID- 24903367
TI  - Intestinal trematode infections.

PMID- 24903368
TI  - Epidemiology of trematode infections.

PMID- 24903369
TI  - Diagnosis of human trematode infections.

PMID- 24903370
TI  - Schistosomatoidea and Diplostomoidea.

PMID- 24903371
TI  - Amphistomes.

PMID- 24903372
TI  - Dicrocoeliidae family: major species causing veterinary diseases.

PMID- 24903373
TI  - Selected wildlife trematodiasis.

PMID- 24903374
TI  - A Review and Analysis of the YODA Trials: What Can We Glean Clinically?
AB  - Medtronic's biologic, Infuse (rhBMP-2), was approved by the FDA in 2002. Since
      its approval, a whirlwind of controversy developed culminating in an
      investigation by the Senate Finance committee. These events led to a landmark
      agreement between Medtronic and Yale University to perform a comprehensive and
      unbiased analysis of all patient related data. The project was named the Yale
      Open Data Access (YODA). The purpose of this article is to evaluate the results
      of the YODA project and determine what is clinically meaningful. 

PMID- 24903375
TI  - Epidemiologic trends in the utilization, demographics, and cost of bone
      morphogenetic protein in spinal fusions.
AB  - Bone morphogenetic protein (BMP) utilization as an adjunct for spinal arthrodesis
      has gained considerable momentum among spine surgeons. Despite carrying Food and
      Drug Administration approval for only single level anterior lumbar interbody
      fusion from L4-S1, the majority of BMP administration is in "off label" settings.
      Over the last decade, BMP utilization has increased in all facets of spine
      surgery with the only exception being the anterior cervical spine, in which a
      downward trend resulted following the 2008 Food and Drug Administration warnings.
      The future application of BMP in spinal fusion, especially in anterior cervical
      fusions, will need to be further clarified in terms of efficacy, complications,
      and cost-effectiveness. 

PMID- 24903377
TI  - Retracted Article: Interference of Mucin 1 inhibits the growth of liver cancer
      cells by inducing mitochondria-mediated and death receptor-mediated cell
      apoptosis.

PMID- 24903376
TI  - TRPM8 promotes aggressiveness of breast cancer cells by regulating EMT via
      activating AKT/GSK-3beta pathway.
AB  - Breast cancer already taken the first place of incidence in Chinese female cancer
      patients. TRPM8 is found to be over-expressed in breast cancer, but whether it
      promotes breast cancer aggressiveness remains unknown. In our study, TRPM8 was
      identified highly expressing in all the tested breast cancer cell lines including
      MCF-7, T47D, MDA-MB-231, BT549, SKBR3 and ZR-75-30, while it just could be
      detected in MCF-10A, the normal breast epithelial cell. Then four pairs of
      clinical samples were analyzed using Western blotting and the result showed that
      TRPM8 expression is higher in tumor tissues than in adjacent nontumor tissues.
      Subsequently, we established TRPM8 high-expressing MCF-7 cell line and TRPM8
      knockout MDA-MB-231 cell line to explore expression status of cancer-related
      proteins. The Western blotting and immunofluorescence analysis outcomes
      demonstrated that TRPM8 might influence cancer cell metastasis by regulating the
      EMT phenotype via activating AKT/GSK-3beta pathway, and the hypothesis had been
      supported by cell function tests. All the results demonstrated that TRPM8
      significantly up-expressed in breast cancer cells and promoted their metastasis
      by regulating EMT via activating AKT/GSK-3beta pathway, indicating TRPM8 gets the
      prospects of to be developed as medication or diagnostic indicator to be applied
      in clinical work.

PMID- 24903379
TI  - A polysaccharide from the fruiting bodies of Agaricus blazei Murill induces
      caspase-dependent apoptosis in human leukemia HL-60 cells.
AB  - Polysaccharides are the major active ingredients of fungus Agaricus blazei for
      treating and preventing cancer. However, there are no reports showing anti-tumor
      activity of A. blazei polysaccharides (ABP) on human leukemia (HL)-60 cells in
      vitro and in vivo. In this study, we demonstrated that ABP efficiently inhibited
      proliferation of cultured HL-60 cells, which was associated with the induction of
      apoptosis. The increase in ABP-induced apoptosis was accompanied by loss of
      mitochondria membrane potential (?Psim), cytochrome c release from the
      mitochondria, activation of caspase-3, degradation of poly(ADP-ribose) polymerase
      (PARP), and the elevated ratio of Bcl-2-associated X (Bax)/B-cell lymphoma 2 (Bcl
      2). Moreover, z-DEVD-fmk, a caspase-3 inhibitor, reversed the cytotoxic effects
      and apoptotic characteristics induced by ABP in HL-60 cells. Furthermore, we
      confirmed that ABP could obviously inhibit the solid cancer growth of leukemia HL
      60 in tumor xenograft model. These data demonstrated that ABP effectively induced
      the apoptosis of HL-60 cells via a signaling cascade of mitochondrial caspase-3
      dependent pathway.

PMID- 24903378
TI  - In vitro antileukaemic activity of extracts from Daphne gnidium leaves against
      sensitive and multidrug resistant K562/R7 cells.
AB  - The antiproliferative potential of extracts of Daphne gnidium L. (Thymelaeaceae)
      on K562 cells was assessed, and the capacity of these extracts to disturb the
      cell cycle of K562 cells and to inhibit human P-glycoprotein was evaluated. The
      antiproliferative activity was evaluated using the MTT assay. The cell cycle
      analysis and the inhibition of P-glycoprotein were tested by flow cytometry. All
      the tested extracts exhibited significant anti-proliferative effects. Ethyl
      acetate extract has the strongest cytotoxic effect with an IC50 of 18.5 MUg/ml.
      Furthermore, cell cycle analysis revealed that cells treated with chloroform,
      butanol and aqueous extracts were arrested predominantly in G2-M phase. Butanol
      extract was the most active extract. Percentage of cells arrested in G2-M was 34
      %, 36.67 % and 42.63 % respectively, after treatment with 25, 75 and 100 MUg/ml
      of the extract, versus 19 % in the cells treated with the vehicle solvent. In
      addition, chloroform extract had the ability to inhibit human P-glycoprotein
      mediated daunorubicin in K562/R7 leukaemic cells in a dose-dependent manner
      compared to the positive control, cyclosporin A. These findings demonstrate that
      extracts from D. gnidium leaves have antileukaemic activity by perturbing the
      cell cycle of K562 and inhibiting human P-glycoprotein in K562/R7 cell line.

PMID- 24903380
TI  - Refute the conclusion made by Jie et al. in "prognostic role of microRNA-100 in
      various carcinomas: evidence from six studies".
AB  - Recently, we had the honor of reading a meta-analysis article published in Tumor
      Biology which was completed by Jie et al. Because of our interest in the
      correlations between microRNAs (miRs) and human cancer prognosis, we carefully
      read the entire article. Jie et al. put forward a standpoint that deregulation of
      miR-100 in cancerous tissues could significantly predict poor survival in various
      carcinomas. The pooled hazard ratio (HR) with 95 % confidence interval (CI) was
      2.19 (1.49-3.24, p = 0.0007). The reliability of the meta-analysis is
      reciprocally higher than traditional and narrative reviews. Furthermore, the
      reliability is exclusively dependent on reference retrieval, incorporating
      eligible articles as comprehensive as possible, and proper and accurate data
      extraction. We found several critical errors in their meta-analysis, and its
      conclusion was unbelievable and might misguide readers. According to their
      statistical strategies, we also conducted a meta-analysis to reevaluate the
      relationship between deregulation of miR-100 and human cancer prognosis for
      rectification. The present studies are not powerful enough to demonstrate the
      prognostic role of miR-100 in human cancers, and thus, much more works are needed
      in this field.

PMID- 24903381
TI  - MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal
      transition in lung adenocarcinoma-initiating cells.
AB  - MicroRNA-145 (MiR-145) is an important regulator of tumorigenesis. Our previous
      work indicated that miR-145 reduced the proliferation and invasion as well as the
      tumorosphere growth capacity in lung adenocarcinoma cells. However, the
      underlying molecular mechanisms remain elusive. Here, we reported that the
      expression level of miR-145 was downregulated in lung adenocarcinoma tissues and
      negatively correlated with the expression level of Oct4. MiR-145 inhibited the
      proliferation of lung cancer-initiating cells (LCICs), partially by regulating
      Oct4 expression. Furthermore, we found that miR-145 exerted repressive effect on
      cancer stem cell properties and inhibited epithelial-mesenchymal transition (EMT)
      in vitro, also partially by regulating Oct4. Finally, we confirmed the repressive
      effect of miR-145 on cancer stem cell properties and EMT in vivo. Taken together,
      these evidences suggest that miR-145 serves as a tumor suppressor which
      downregulates LCICs' cancer stem cell properties and EMT process by targeting
      Oct4, leading to the inhibition of tumor growth and metastasis.

PMID- 24903382
TI  - Silencing of Src by siRNA inhibits laryngeal carcinoma growth through the Src/PI
      3 K/Akt pathway in vitro and in vivo.
AB  - This study aimed to investigate the expression, function, and possible mechanism
      of Src in the Hep-2 cell line. We used Src-specific small interfering RNA (siRNA)
      to inhibit the expression of Src in Hep-2 cells. RT-PCR and Western blot were
      applied to evaluate the expression level of Src after RNA interference, and the
      MTT assay and flow cytometry were used to observe the expression of PI-3 K and
      Akt. siRNA can downregulate the expression of Src in Hep-2 cells. Downregulation
      of Src decreased PI-3 K and Akt expression. We found that Src knockdown inhibits
      the proliferation of Hep-2 cells and the growth of laryngeal carcinoma in vivo.
      This study has demonstrated that Src participates in the regulation of apoptosis
      through the Src/PI-3 K/Akt signaling pathway in the Hep-2 cell line. Silencing of
      Src by siRNA is a viable approach in laryngeal carcinoma treatment.

PMID- 24903383
TI  - TIMP-3 -1296 T>C and TIMP-4 -55 T>C gene polymorphisms play a role in the
      susceptibility of hepatocellular carcinoma among women.
AB  - The purpose of this study was to investigate genetic impact of TIMP-3 -1296 T>C
      (rs9619311) and TIMP-4 -55 T>C (rs3755724) gene polymorphisms on the
      susceptibility and clinicopathological characteristics of hepatocellular
      carcinoma (HCC). A total of 759 subjects, including 530 healthy controls and 229
      patients with hepatocellular carcinoma, were recruited in this study. Allelic
      discrimination of TIMP-3 -1296 T>C (rs9619311) and TIMP-4 -55 T>C (rs3755724)
      polymorphisms was assessed with the ABI StepOneTM Real-Time PCR System. Among
      women group, individuals with TC or CC alleles of TIMP-3 -1296 T>C gene
      polymorphism protected against HCC (AOR = 0.35, 95% confidence interval (CI) =
      0.12-0.97; p = 0.04) compared to individuals with TT alleles, after adjusting for
      other confounders. Also, women with TC alleles and with TC or CC alleles of TIMP
      4 -55 T>C polymorphisms had a 2.52-fold risk (95%CI = 1.23-5.13; p = 0.01) and
      2.47-fold risk (95%CI = 1.26-4.87; p = 0.008) of developing HCC compared to
      individuals with TT alleles, after adjusting for other confounders. There was no
      synergistic effect between gene polymorphism and environmental risk factors,
      including tobacco and alcohol consumptions and clinical statuses of HCC as well
      as serum expression of liver-related clinicopathological markers. In conclusion,
      gene polymorphisms of TIMP-3 -1296 T>C (rs9619311) and TIMP-4 -55 T>C (rs3755724)
      play a role in the susceptibility of HCC among Taiwan women.

PMID- 24903384
TI  - The role of sphingosine kinase isoforms and receptors S1P1, S1P2, S1P3, and S1P5
      in primary, secondary, and recurrent glioblastomas.
AB  - Sphingosine-1-phosphate (S1P), the corresponding kinases SphK1-2, and receptors
      S1P1-3 and S1P5 are involved in cell survival and growth. Pathway components are
      overexpressed in many tumors including glioblastoma. Previous studies showed that
      the expression of SphK1 influenced survival of glioblastoma patients, yet the
      roles of SphK1-2 and receptors S1P1-3 and S1P5 have not been investigated in
      different forms of glioblastoma. Samples from 59 patients (37 males, 22 females,
      age 55.1 +/- 17.1 years) suffering from primary (n = 35), recurrent (n = 18), and
      secondary (n = 6) glioblastomas were analyzed using quantitative real-time PCR
      and immunohistochemistry for expression levels of SphK1 and SphK2 and S1P1-3 and
      S1P5. Sixteen autopsy nontumorous brain specimens were used as controls.
      Expression data was correlated with clinical data and patient survival. All
      markers were overexpressed in the glioblastoma specimens compared to the non
      neoplastic brain tissue. SphK1 and all S1P receptors were expressed in increasing
      order of magnitude from primary, up to recurrent and secondary glioblastomas,
      with values of up to 44-fold compared to normal brain tissue. In contrast, SphK2
      levels were highest in primary tumors (25-fold). Expression of the sphingosine
      signaling pathway components was influenced by radio/radiochemotherapy in
      distinct ways. Immunohistochemistry for SphK1 and S1P1 confirmed the
      overexpression in glioblastoma. Uni- and multivariate survival analyses
      identified S1P5 messenger RNA levels as an independent prognostic factor of
      survival. The sphingosine pathway is overexpressed in glioma. Its components show
      distinct expression patterns in the tumor subgroups. S1P5 is identified as an
      independent prognostic factor in multivariate analysis, and this pathway promises
      to be a candidate for targeted therapies.

PMID- 24903385
TI  - Upper gastrointestinal bleeding in patients with CKD.
AB  - BACKGROUND AND OBJECTIVES: Patients with CKD receiving maintenance dialysis are
      at risk for upper gastrointestinal bleeding. However, the risk of upper
      gastrointestinal bleeding in patients with early CKD who are not receiving
      dialysis is unknown. The hypothesis was that their risk of upper gastrointestinal
      bleeding is negatively linked to renal function. To test this hypothesis, the
      association between eGFR and risk of upper gastrointestinal bleeding in patients
      with stages 3-5 CKD who were not receiving dialysis was analyzed. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with stages 3-5 CKD in the CKD
      program from 2003 to 2009 were enrolled and prospectively followed until December
      of 2012 to monitor the development of upper gastrointestinal bleeding. The risk
      of upper gastrointestinal bleeding was analyzed using competing-risks regression
      with time-varying covariates. RESULTS: In total, 2968 patients with stages 3-5
      CKD who were not receiving dialysis were followed for a median of 1.9 years. The
      incidence of upper gastrointestinal bleeding per 100 patient-years was 3.7 (95%
      confidence interval, 3.5 to 3.9) in patients with stage 3 CKD, 5.0 (95%
      confidence interval, 4.8 to 5.3) in patients with stage 4 CKD, and 13.9 (95%
      confidence interval, 13.1 to 14.8) in patients with stage 5 CKD. Higher eGFR was
      associated with a lower risk of upper gastrointestinal bleeding (P=0.03), with a
      subdistribution hazard ratio of 0.93 (95% confidence interval, 0.87 to 0.99) for
      every 5 ml/min per 1.73 m(2) higher eGFR. A history of upper gastrointestinal
      bleeding (P<0.001) and lower serum albumin (P=0.004) were independently
      associated with higher upper gastrointestinal bleeding risk. CONCLUSIONS: In
      patients with CKD who are not receiving dialysis, lower renal function is
      associated with higher risk for upper gastrointestinal bleeding. The risk is
      higher in patients with previous upper gastrointestinal bleeding history and low
      serum albumin.

PMID- 24903386
TI  - Patient-stated preferences regarding volume-related risk mitigation strategies
      for hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Larger weight gain and higher ultrafiltration rates
      have been associated with poorer outcomes among patients on dialysis. Dietary
      restrictions reduce fluid-related risk; however, adherence is challenging.
      Alternative fluid mitigation strategies include treatment time extension, more
      frequent dialysis, adjunct peritoneal dialysis, and wearable ultrafiltration
      devices. No data regarding patient preferences for fluid management exist. A
      survey was designed, tested, and administered to assess patient-stated
      preferences regarding fluid mitigation. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: A written survey concerning fluid-related symptoms, patient and
      treatment characteristics, and fluid management preferences was developed. The
      cross-sectional survey was completed by 600 patients on hemodialysis at 18
      geographically diverse ambulatory facilities. Comparisons of patient willingness
      to engage in volume mitigation strategies across fluid symptom burden, dietary
      restriction experience, and patient characteristics were performed. RESULTS:
      Final analyses included 588 surveys. Overall, if allowed to liberalize fluid
      intake, 44.6% of patients were willing to extend treatment time by 15 minutes.
      Willingness to extend treatment time was incrementally less for longer treatment
      extensions; 12.2% of patients were willing to add a fourth weekly treatment
      session, and 13.5% of patients were willing to participate in nocturnal dialysis
      three nights per week. Patients more bothered by their fluid restrictions (versus
      less bothered) were more willing to engage in fluid mitigation strategies.
      Demographic characteristics and symptoms, such as cramping and dyspnea, were not
      consistently associated with willingness to engage in the proposed strategies.
      More than 25% of patients were unsure of their dry weights and typical
      interdialytic weight gains. CONCLUSIONS: Patients were generally averse to
      treatment time extension>15 minutes. Patients more bothered (versus less
      bothered) by their prescribed fluid restrictions were more willing to engage in
      volume mitigation strategies. Additional study of patient-stated preferences in
      hemodialysis treatment practices is needed to guide patient care and identify
      deficiencies in patient treatment and disease-related knowledge.

PMID- 24903387
TI  - Use of renin-angiotensin inhibitors in people with renal artery stenosis.
AB  - BACKGROUND AND OBJECTIVES: People with atherosclerotic renal artery stenosis may
      benefit from renin-angiotensin inhibitors, angiotensin-converting enzyme
      inhibitors, and angiotensin-receptor blockers, but little is known about the
      factors associated with their use. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      The Cardiovascular Outcomes in Renal Atherosclerotic Lesions study
      (ClinicalTrials.gov identified: NCT00081731) is a prospective, international,
      multicenter clinical trial that randomly assigned participants with
      atherosclerotic renal artery stenosis who received optimal medical therapy to
      stenting versus no stenting from May 2005 through January 2010. At baseline,
      medication information was available from 853 of 931 randomly assigned
      participants. Kidney function was measured by serum creatinine-based eGFR at a
      core laboratory. RESULTS: Before randomization, renin-angiotensin inhibitors were
      used in 419 (49%) of the 853 participants. Renin-angiotensin inhibitor use was
      lower in those with CKD (eGFR<60 ml/min per 1.73 m(2)) (58% versus 68%; P=0.004)
      and higher in individuals with diabetes (41% versus 27%; P<0.001). Presence of
      bilateral renal artery stenosis or congestive heart failure was not associated
      with renin-angiotensin inhibitor use. Although therapy with renin-angiotensin
      inhibitors varied by study site, differences in rates of use were not related to
      the characteristics of the site participants. Participants receiving a renin
      angiotensin inhibitor had lower systolic BP (mean +/- SD, 148 +/- 23 versus 152
      +/- 23 mmHg; P=0.003) and more often had BP at goal (30% versus 22%; P=0.01).
      CONCLUSIONS: Kidney function and diabetes were associated with renin-angiotensin
      inhibitor use. However, these or other clinical characteristics did not explain
      variability among study sites. Patients with renal artery stenosis who received
      renin-angiotensin inhibitor treatment had lower BP and were more likely to be at
      treatment goal.

PMID- 24903388
TI  - Kidney transplant failure: failing kidneys, failing care?

PMID- 24903389
TI  - Use of renin-angiotensin system blockade in patients with renal artery stenosis.

PMID- 24903391
TI  - Filling the holes in cystic kidney disease research.
AB  - Kidney disease is a significant medical and public health problem. The National
      Institute of Diabetes and Digestive and Kidney Diseases recently asked the
      community to identify research objectives, which, if addressed, could improve
      understanding of basic kidney function and aid in prevention, treatment, and
      reversal of kidney disease. The Kidney Research National Dialogue invited
      interested parties to submit, discuss, and prioritize ideas using an interactive
      website; 1600 participants posted more than 300 ideas covering all areas of
      kidney disease, including the cystic kidney diseases. Although much is known
      about the genetics and pathogenesis of cystic diseases, there remain challenges
      to our understanding of the fundamental mechanisms of cyst formation, what genes
      act as modifiers to cause variable responses in different people, and how to
      detect and monitor disease progression. This article summarizes key research
      questions for cystic kidney diseases. 

PMID- 24903390
TI  - Gene-gene and gene-environment interactions in apolipoprotein L1 gene-associated
      nephropathy.
AB  - Molecular genetics have revolutionized the understanding of susceptibility to the
      broad spectrum of kidney diseases with light microscopic appearance of FSGS,
      particularly in populations with recent African ancestry. These disorders include
      idiopathic FSGS, HIV-associated nephropathy, severe lupus nephritis, sickle cell
      nephropathy, and the primary kidney disorder focal global glomerulosclerosis,
      which had historically been ascribed to systemic hypertension. FSGS was once
      thought to include a multitude of unrelated disorders with similar histologic
      appearance. However, variation in the apolipoprotein L1 gene locus is now known
      to account for the vast majority of such cases in African Americans as well as
      nearly all the excess risk for FSGS and related forms of progressive nondiabetic
      nephropathy in populations with recent African ancestry, relative to European
      ancestry. Inheriting two coding apolipoprotein L1 gene nephropathy risk variants
      is necessary for susceptibility to CKD; however, these variants alone are
      insufficient to produce disease. This work reviews the evidence supporting second
      hits or modifying factors that affect risk for apolipoprotein L1 gene-associated
      nephropathy and produce the protean manifestations of this common and complex
      syndrome. Targeting modifiable second factors will lead to preventive therapies
      for slowing progression of nondiabetic nephropathy in many patients possessing
      two apolipoprotein L1 gene risk variants. This model of genetic risk coupled with
      modifiable second hits will serve as a paradigm applicable to patients with CKD
      of various etiologies as well as a host of other complex disorders. 

PMID- 24903393
TI  - Subclavian artery dissection presenting as non-ST elevation myocardial
      infarction.
AB  - Spontaneous subclavian artery dissection is rarely reported. We report the case
      of a 55-year-old female who presented as an non-ST elevation myocardial
      infarction (NSTEMI) and was found to have a proximal left subclavian dissection.
      We provide an overview of current articles addressing the clinical features and
      treatments of subclavian dissection. To our knowledge, this is the first report
      of subclavian dissection presenting as an NSTEMI.

PMID- 24903392
TI  - Initial vascular access type in patients with a failed renal transplant.
AB  - BACKGROUND AND OBJECTIVES: Permanent hemodialysis vascular access is crucial for
      RRT in ESRD patients and patients with failed renal transplants, because central
      venous catheters are associated with greater risk of infection and mortality than
      arteriovenous fistulae or arteriovenous grafts. The objective of this study was
      to determine the types of vascular access used by patients initiating
      hemodialysis after a failed renal transplant. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Data from the US Renal Data System database on 16,728 patients with
      a failed renal transplant and 509,643 patients with native kidney failure who
      initiated dialysis between January 1, 2006, and September 30, 2011 were examined.
      RESULTS: At initiation of dialysis, of patients with a failed transplant, 27.7%
      (n=4636) used an arteriovenous fistula, 6.9% (n=1146) used an arteriovenous
      graft, and 65.4% (n=10,946) used a central venous catheter. Conversely, 80.8%
      (n=411,997) of patients with native kidney failure initiated dialysis with a
      central venous catheter (P<0.001). Among patients with a failed transplant,
      predictors of central venous catheter use included women (adjusted odds ratio,
      1.75; 95% confidence interval, 1.63 to 1.87), lack of referral to a nephrologist
      (odds ratio, 2.00; 95% confidence interval, 1.72 to 2.33), diabetes (odds ratio,
      1.14; 95% confidence interval, 1.06 to 1.22), peripheral vascular disease (odds
      ratio, 1.31; 95% confidence interval, 1.16 to 1.48), and being institutionalized
      (odds ratio, 1.53; 95% confidence interval, 1.23 to 1.89). Factors associated
      with lower odds of central venous catheter use included older age (odds ratio,
      0.85 per 10 years; 95% confidence interval, 0.83 to 0.87), public insurance (odds
      ratio, 0.74; 95% confidence interval, 0.68 to 0.80), and current employment (odds
      ratio, 0.87; 95% confidence interval, 0.80 to 0.95). CONCLUSIONS: Central venous
      catheters are used in nearly two thirds of failed renal transplant patients.
      These patients are usually followed closely by transplant physicians before
      developing ESRD after a failed transplant, but the relatively low prevalence of
      arteriovenous fistulae/arteriovenous grafts in this group at initiation of
      dialysis needs to be investigated more thoroughly.

PMID- 24903394
TI  - Comments on: Overview of object oriented data analysis.
AB  - This is a discussion on the paper: "Overview of Object Oriented Data Analysis" by
      J. Steve Marron and Andres M. Alonso. 

PMID- 24903395
TI  - Intraspinal canal rod migration causing late-onset paraparesis 8 years after
      scoliosis surgery.
AB  - INTRODUCTION: Complete intraspinal canal rod migration with posterior bone
      reconstitution has never been described in the adolescent idiopathic scoliosis
      (AIS) population. We present an unusual but significant delayed neurological
      complication after spinal instrumentation surgery. CASE REPORT: A 24-year-old
      woman presented with lower limb weakness (ASIA D) 8 years after posterior
      instrumentation from T2 to L4 for AIS. CT scan and MRI demonstrated intra-canal
      rod migration with complete laminar reconstitution. The C-reactive protein was
      slightly elevated (fluctuated between 10 and 20 mg/l). Radiographs showed the
      convex rod had entered the spinal canal. The patient was taken into the operating
      room for thoracic spinal decompression and removal of the convex rod. This Cotrel
      Dubousset rod, which had been placed on the convexity of the thoracic curve had
      completely entered the canal from T5 to T10 and was totally covered by bone with
      the eroded laminae entirely healed and closed. There was no pseudarthrosis. Intra
      operatively, the fusion mass was opened along the whole length of this rod and
      the rod carefully removed and the spinal cord decompressed. The bacteriological
      cultures returned positive for Propionibacterium acnes. The patient recovered
      fully within 2 months post-operatively. CONCLUSION: We opine that the progressive
      laminar erosion with intra-canal rod migration resulted from mechanical and
      infectious-related factors. The very low virulence of the strain of
      Propionibacterium acnes is probably involved in this particular presentation
      where the rod was trapped in the canal, owing to the quite extensive laminar
      reconstitution.

PMID- 24903397
TI  - Poly-benzylic ammonium chloride resins as solid catalysts for fructose
      dehydration.
AB  - 5-hydroxymethylfurfural (HMF) is one of the most promising platform molecules,
      and can be converted into a variety of interesting chemicals. The production of
      HMF is essentially targeted at bulk chemicals downstream, such as chemicals for
      the fuels and plastics industries. One critical challenge in HMF production
      processes is the link to further value-adding reactions in a simple and efficient
      way (e.g., fewer isolation and purification steps). Herein, a novel poly-benzyl
      ammonium chloride (PBnNH3 Cl) resin is developed as a highly efficient and stable
      catalyst for dehydration of carbohydrates into HMF. In the isopropanol system,
      PBnNH3 Cl produces high purity HMF that is suitable as feedstock for oxidation to
      2,5-furandicarboxylic acid (FDCA). The excellent catalytic properties together
      with its easy synthesis, low cost, and nontoxic nature make this poly-ammonium
      resin a promising catalyst for the development of new and efficient processes for
      biomass-based chemicals. 

PMID- 24903396
TI  - Evaluation of impingement behaviour in lumbar spinal disc arthroplasty.
AB  - INTRODUCTION: The objective of our in vitro study was to introduce a test method
      to evaluate impingement in lumbar spinal disc arthroplasty in terms of wear,
      contact pattern, metal ion concentration and particle release. MATERIAL AND
      METHOD: Impingement wear simulation was performed on a 6-station spinal wear
      simulator (Endolab, Germany) on a lumbar spinal disc system (activ L Aesculap AG,
      Germany) using four different protocols specific to impingement in flexion, in
      extension, in lateral bending and in combined flexion bending. Impingement
      contact stress is intentionally created by applying an angular displacement of +2
      degrees  in addition to the intended range of motion in the impingement
      direction, whereas a bending moment of 8 Nm remains constant during the
      impingement phase (plateau). RESULTS: An average volumetric wear rate of 0.67
      mm(3)/million cycles was measured by impingement under flexion, of 0.21
      mm(3)/million cycles under extension, of 0.06 mm(3)/million cycles under lateral
      bending and of 1.44 mm(3)/million cycles under combined flexion bending. The
      particle size distribution of the cobalt-chromium wear particles released by
      impingement in flexion (anterior), extension (posterior), lateral bending
      (lateral) and combined flexion bending (antero-lateral) revealed that most of the
      detected cobalt-chromium particles were in a size range between 0.2 and 2 um.
      CONCLUSION: The impingement wear simulation introduced here proved to be suitable
      to predict in vivo impingement behaviour in regard to contact pattern seen on
      retrieved devices of the activ L lumbar disc arthroplasty design in a pre
      clinical test.

PMID- 24903398
TI  - Intercollegiate Athletes and Sexual Violence: A Review of Literature and
      Recommendations for Future Study.
AB  - The 1990s saw the development of research on violence against women perpetrated
      by intercollegiate student-athletes. Research in this field stagnated during the
      last 15 years, despite the fact that this time period has evidenced multiple high
      profile, even fatal, cases of violence against women at the hands of male student
      athletes. These events prompted the Office of Civil Rights to call upon
      universities to more appropriately investigate and sanction perpetrators of
      sexual assault. The ensuing actions by universities are expected to bring a
      renewed focus on male student-athletes, requiring further research to explore
      student-athletes sexually abusing women. This article outlines the pertinent
      literature on violence against women by male student-athletes, and suggests
      future research using new institutionalism as a theoretical framework. 

PMID- 24903399
TI  - Pathways From Bullying Perpetration, Victimization, and Bully Victimization to
      Suicidality Among School-Aged Youth: A Review of the Potential Mediators and a
      Call for Further Investigation.
AB  - In the wake of several highly publicized adolescent suicides attributed to
      bullying victimization, national attention has been brought to bear on the
      profound public health problem of bullying. This article reviews the extant
      literature on the associations between bullying perpetration, victimization, and
      thoughts of or attempts at suicide and proposes five potential mediators, namely
      depression, anxiety, low self-esteem, loneliness, and hopelessness, that may
      explain this relationship. Numerous studies have found empirical support for the
      interrelations between internalizing behaviors and both bullying perpetration and
      victimization and suicide. We find that further longitudinal research needs to be
      conducted to more conclusively determine the role and causal ordering these
      various psychosocial factors may play in bullying perpetration, victimization,
      and suicide. Although the research literature implies causal directions among all
      these potential mediators, untangling the unique influence of bullying
      perpetration, victimization, and bully victimization on suicide and its
      mechanisms of action has major research and practice implications. 

PMID- 24903400
TI  - Adult Disclosure of Child Sexual Abuse: A Literature Review.
AB  - Victims of childhood sexual abuse carry the experience of abuse into adulthood.
      One of the dilemmas victims face during adulthood is the decision to disclose or
      conceal the abuse. Although adult disclosure may be affected by former disclosure
      during childhood, adult survivors face new challenges and dilemmas, such as to
      whom, when, and how to tell. The purpose of this article is to review the domains
      found in the literature on survivors' experiences regarding disclosure of child
      sexual abuse during adulthood, all of which were published between 1980 and 2013.
      Domains include decisions to disclose during adulthood, barriers and facilitators
      to disclosure and potential recipients of the disclosure, as well as the process
      of telling and its impact on survivors' well-being. The authors present
      implications for policy, practice, and research. 

PMID- 24903401
TI  - Stroke patients' utilisation of extrinsic feedback from computer-based technology
      in the home: a multiple case study realistic evaluation.
AB  - BACKGROUND: Evidence indicates that post-stroke rehabilitation improves function,
      independence and quality of life. A key aspect of rehabilitation is the provision
      of appropriate information and feedback to the learner.Advances in information
      and communications technology (ICT) have allowed for the development of various
      systems to complement stroke rehabilitation that could be used in the home
      setting. These systems may increase the provision of rehabilitation a stroke
      survivor receives and carries out, as well as providing a learning platform that
      facilitates long-term self-managed rehabilitation and behaviour change. This
      paper describes the application of an innovative evaluative methodology to
      explore the utilisation of feedback for post-stroke upper-limb rehabilitation in
      the home. METHODS: Using the principles of realistic evaluation, this study aimed
      to test and refine intervention theories by exploring the complex interactions of
      contexts, mechanisms and outcomes that arise from technology deployment in the
      home. Methods included focus groups followed by multi-method case studies (n = 5)
      before, during and after the use of computer-based equipment. Data were analysed
      in relation to the context-mechanism-outcome hypotheses case by case. This was
      followed by a synthesis of the findings to answer the question, 'what works for
      whom and in what circumstances and respects?' RESULTS: Data analysis reveals that
      to achieve desired outcomes through the use of ICT, key elements of computer
      feedback, such as accuracy, measurability, rewarding feedback, adaptability, and
      knowledge of results feedback, are required to trigger the theory-driven
      mechanisms underpinning the intervention. In addition, the pre-existing context
      and the personal and environmental contexts, such as previous experience of
      service delivery, personal goals, trust in the technology, and social
      circumstances may also enable or constrain the underpinning theory-driven
      mechanisms. CONCLUSIONS: Findings suggest that the theory-driven mechanisms
      underpinning the utilisation of feedback from computer-based technology for home
      based upper-limb post-stroke rehabilitation are dependent on key elements of
      computer feedback and the personal and environmental context. The identification
      of these elements may therefore inform the development of technology; therapy
      education and the subsequent adoption of technology and a self-management
      paradigm; long-term self-managed rehabilitation; and importantly, improvements in
      the physical and psychosocial aspects of recovery.

PMID- 24903403
TI  - Stenosing proctitis with subsequent colostomy placement.

PMID- 24903405
TI  - Genomic full-length sequence of two HLA-A alleles, A*02:01:01:01 and A*02:03:01,
      identified by cloning and sequencing.
AB  - Genomic full-length sequences of HLA-A*02:01:01:01 and HLA-A*02:03:01 were
      identified by cloning and sequencing from two Chinese donors. 

PMID- 24903402
TI  - Zinc protects against Shiga-toxigenic Escherichia coli by acting on host tissues
      as well as on bacteria.
AB  - BACKGROUND: Zinc supplements can treat or prevent enteric infections and
      diarrheal disease. Many articles on zinc in bacteria, however, highlight the
      essential nature of this metal for bacterial growth and virulence, suggesting
      that zinc should make infections worse, not better. To address this paradox, we
      tested whether zinc might have protective effects on intestinal epithelium as
      well as on the pathogen. RESULTS: Using polarized monolayers of T84 cells we
      found that zinc protected against damage induced by hydrogen peroxide, as
      measured by trans-epithelial electrical resistance. Zinc also reduced peroxide
      induced translocation of Shiga toxin (Stx) across T84 monolayers from the apical
      to basolateral side. Zinc was superior to other divalent metals to (iron,
      manganese, and nickel) in protecting against peroxide-induced epithelial damage,
      while copper also showed a protective effect.The SOS bacterial stress response
      pathway is a powerful regulator of Stx production in STEC. We examined whether
      zinc's known inhibitory effects on Stx might be mediated by blocking the SOS
      response. Zinc reduced expression of recA, a reliable marker of the SOS. Zinc was
      more potent and more efficacious than other metals tested in inhibiting recA
      expression induced by hydrogen peroxide, xanthine oxidase, or the antibiotic
      ciprofloxacin. The close correlation between zinc's effects on recA/SOS and on
      Stx suggested that inhibition of the SOS response is one mechanism by which zinc
      protects against STEC infection. CONCLUSIONS: Zinc's ability to protect against
      enteric bacterial pathogens may be the result of its combined effects on host
      tissues as well as inhibition of virulence in some pathogens. Research focused
      solely on the effects of zinc on pathogenic microbes may give an incomplete
      picture by failing to account for protective effects of zinc on host epithelia.

PMID- 24903406
TI  - Selective wetting-induced micro-electrode patterning for flexible micro
      supercapacitors.
AB  - Selective wetting-induced micro-electrode patterning is used to fabricate
      flexible micro-supercapacitors (mSCs). The resulting mSCs exhibit high
      performance, mechanical stability, stable cycle life, and hold great promise for
      facile integration into flexible devices requiring on-chip energy storage. 

PMID- 24903407
TI  - Complex disruption effect of natural polyphenols on Bcl-2-Bax: molecular dynamics
      simulation and essential dynamics study.
AB  - Apoptosis (programmed cell death) is a process by which cells died after
      completing physiological function or after a severe genetic damage. Apoptosis is
      mainly regulated by the Bcl-2 family of proteins. Anti apoptotic protein Bcl-2
      prevents the Bax activation/oligomerization to form heterodimer which is
      responsible for release of the cytochrome c from mitochondria to the cytosol in
      response to death signal. Quercetin and taxifolin (natural polyphenols)
      efficiently bound to hydrophobic groove of Bcl-2 and altered the structure by
      inducing conformational changes. Taxifolin was found more efficient when compared
      to quercetin in terms of interaction energy and collapse of hydrophobic groove.
      Taxifolin and quercetin were found to dissociate the Bcl-2-Bax complex during 12
      ns MD simulation. The effect of taxifolin and quercetin was, further validated by
      the MD simulation of ligand-unbound Bcl-2-Bax which showed stability during the
      simulation. Obatoclax (an inhibitor of Bcl-2) had no significant dissociation
      effect on Bcl-2-Bax during simulation which favored the previous experimental
      results and disruption effect of taxifolin and quercetin. 

PMID- 24903408
TI  - Associations between the home environment and children's sweet beverage
      consumption at 2-year follow-up: the 'Be active, eat right' study.
AB  - BACKGROUND: This study evaluates the association between home environmental
      characteristics and sweet beverage consumption (i.e. beverages that contain
      sugar) of 7-year-old children. METHODS: The population for analysis consisted of
      n = 2047 parents and their children from the population-based 'Be active, eat
      right' study. Data on sociodemographic characteristics, parental beliefs,
      parenting practices and child's sweet beverage consumption were obtained by
      parental report with questionnaires. We performed linear and multinomial
      regression analyses evaluating associations between characteristics at age 5
      years and (i) consumption at 7 years and (ii) consumption patterns between age 5
      and 7 years with reference category 'low consumption'. RESULTS: Based on the
      report from their parents, 5-year-old children drank on average 3.0 (SD:1.4)
      sweet beverage per day. Children consumed less sweet beverages at age 7 years
      (beta -0.16, 95% confidence interval [CI] -0.24 to -0.09) when there were less
      sweet beverages available at home. The multinomial regression model showed that
      children with parents who discouraged sweet beverage consumption were more likely
      to decrease their sweet beverage consumption over the study period (odds ratio:
      1.24, 95% CI 1.07 to 1.43). Moreover, when there were less sweet beverages
      available at home, children were less likely to increase their consumption or
      have a high consumption over the study period (odds ratio: 0.70, 95% CI 0.59 to
      0.83 and 0.61, 95% CI 0.54 to 0.70, respectively). CONCLUSIONS: The results
      showed that characteristics of the home environment are associated with the
      consumption of sweet beverages among children. Specifically, the availability of
      sweet beverages at home is associated with the child's sweet beverage
      consumption.

PMID- 24903409
TI  - MRI and (31)P magnetic resonance spectroscopy hardware for axillary lymph node
      investigation at 7T.
AB  - PURPOSE: Neoadjuvant treatment response in lymph nodes predicts patient outcome,
      but existing methods do not track response during therapy accurately. In this
      study, specialized hardware was used to adapt high-field (7T) (31) P magnetic
      resonance spectroscopy (MRS), which has been shown to track treatment response in
      small breast tumors, to monitor axillary lymph nodes. METHOD: A dual-tuned
      quadrature coil that is a (31) P (120 MHz) transceiver and a (1) H (300 MHz)
      receiver was designed using a novel detune circuit. The transceiver/receiver coil
      in the axilla is used with a fractionated dipole antenna on the back of the
      subject and the conventional breast coil for transmit. RESULTS: The novel circuit
      detuned the (1) H resonance without disturbing the (31) P resonance. In vivo
      demonstrations included: >80% homogeneous B1 (+) for (1) H over the axilla,
      identification of a small (3-mm diameter) lymph node, and (31) P MR spectra from
      a single healthy lymph node. The setup can detect <2 millimolar concentrations of
      metabolites from a 2-mL voxel. CONCLUSIONS: The first (31) P MR spectrum from an
      in vivo lymph node indicates that the presented design may be sufficiently
      sensitive to detect metabolic response to neoadjuvant therapy. Multinuclei MRS of
      the lymph nodes at 7T is possible through combining lightweight antenna elements
      with dual-tuned transceiver/receive-only coils.

PMID- 24903410
TI  - Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high
      osmolarity glycerol pathways and regulates multiple stress responses and
      secondary metabolism in Fusarium graminearum.
AB  - Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors
      of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress
      resistance, longevity and nutrient sensing. However, the functions of Sch9
      orthologs in filamentous fungi, particularly in pathogenic species, have not been
      characterized to date. Here, we investigated biological and genetic functions of
      FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (DeltaFgSch9) was
      defective in aerial hyphal growth, hyphal branching and conidial germination. The
      mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell
      wall-damaging agents, and to rapamycin, while showing increased thermal
      tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that
      plays an important role in regulating mycotoxin biosynthesis and virulence of F.
      graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays
      showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both
      DeltaFgSch9 and FgHog1 null mutant (DeltaFgHog1) exhibited increased sensitivity
      to osmotic and oxidative stresses. This defect was more severe in the
      FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a
      mediator of the TOR and high osmolarity glycerol pathways, and regulates
      vegetative differentiation, multiple stress responses and secondary metabolism in
      F. graminearum. 

PMID- 24903411
TI  - Regional frequency analysis of extreme groundwater levels.
AB  - Flood risk is generally perceived as being a consequence of surface water
      inundation. However, large damage is also caused by high groundwater levels. In
      surface hydrology, statistical frequency analysis is a standard tool to estimate
      discharge with a given return period or exceedance probability. First, a suitable
      probability distribution is fit to a series of annual maximum peaks. Second, this
      distribution is used to determine the discharge corresponding to the desired
      return period. Where only short series of recorded data are available, the
      estimates can often be improved by regional frequency analysis (RFA).
      Unfortunately, there is little information in the literature on analogous
      approaches for the estimation of extreme groundwater levels. In this
      contribution, the applicability of l-moments-based RFA for the estimation of
      extreme groundwater levels is investigated. The main issues specific to
      groundwater levels are (1) appropriate transformation of the data, (2) criteria
      for identification of statistically homogeneous regions, (3) consideration of
      correlation between sites, and (4) choice of distribution function. This study is
      based on data from more than 1100 observation sites in four shallow Austrian
      Aquifers with a record length of 10 to 50 years. Results show that homogeneous
      regions for l-moments-based RFA can be identified covering about one half of the
      total area of the aquifers. The confidence intervals for the 30- and 100-year
      return levels can be significantly reduced by RFA. Out of the four investigated
      distribution functions, none is to be preferred generally. 

PMID- 24903413
TI  - Computer-aided discovery of Trypanosoma brucei RNA-editing terminal uridylyl
      transferase 2 inhibitors.
AB  - Human African trypanosomiasis (HAT) is a major health problem in sub-Saharan
      Africa caused by Trypanosoma brucei infection. Current HAT drugs are difficult to
      administer and not effective against all parasite species at different stages of
      the disease which indicates an unmet pharmaceutical need. TbRET2 is an
      indispensable enzyme for the parasite and is targeted here using a computational
      approach that combines molecular dynamics simulations and virtual screening. The
      compounds prioritized are then tested in T. brucei via Alamar blue cell viability
      assays. This work identified 20 drug-like compounds which are candidates for
      further testing in the drug discovery process. 

PMID- 24903412
TI  - Identification of an old antibiotic clofoctol as a novel activator of unfolded
      protein response pathways and an inhibitor of prostate cancer.
AB  - BACKGROUND AND PURPOSE: Finding new indications for existing drugs, also known as
      drug repositioning or repurposing, is a powerful approach to accelerate drug
      discovery and development. The unfolded protein response pathways have been
      proposed to be a viable target for developing new anticancer drugs. EXPERIMENTAL
      APPROACH: We screened the Johns Hopkins Drug Library for inhibitors of prostate
      cancer cell proliferation to identify new antiprostate cancer treatments among
      known drugs. We systematically investigated the mechanism underlying the
      anticancer activity of a hit and assessed its efficacy in blocking prostate
      tumour growth in a mouse model. KEY RESULTS: The antibacterial drug clofoctol was
      identified as a novel inhibitor of prostate cancer cell proliferation.
      Morphologically, cells treated with clofoctol were found to undergo massive
      vacuolization, reminiscent of endoplasmic reticulum stress. Indeed, all three
      unfolded protein response pathways including inositol requiring enzyme 1, double
      stranded RNA-activated PK-like ER kinase and activating transcription factor 6
      were found to be activated by clofoctol. Activation of unfolded protein response
      pathways by clofoctol led to the inhibition of protein translation in cells and
      the induction of G1 cell cycle arrest in prostate cancer cells. Clofoctol also
      inhibited prostate cancer xenograft growth in vivo without apparent toxicity.
      CONCLUSION AND IMPLICATIONS: Our findings revealed clofoctol as a novel activator
      of the unfolded protein response pathways and a promising inhibitor of prostate
      cancer. As clofoctol has been used in the clinic for years, it is ready for
      clinical evaluation as a novel antiprostate cancer drug candidate.

PMID- 24903415
TI  - My Outsider Art.

PMID- 24903414
TI  - Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1
      family study.
AB  - BACKGROUND: Twin and multiplex family studies have established significant
      heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on
      the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct
      the genetic architecture of SZ using neurocognitive and neurophysiological
      endophenotypes, for which heritability estimates ranged from 18% to 50% (mean =
      30%). This study assessed the heritability of SZ in these families to determine
      whether there is a "heritability gap" between the diagnosis and related
      endophenotypes. METHODS: Nuclear families (N = 296) with a SZ proband, an
      unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6)
      underwent comprehensive endophenotype and clinical characterization. The Family
      Interview for Genetic Studies was administered to all participants and used to
      obtain convergent psychiatric symptom information for additional first-degree
      relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2).
      Heritability estimates of psychotic disorders were computed for both nuclear and
      extended families. RESULTS: The heritability of SZ was 31% and 44% for nuclear
      and extended families. The inclusion of bipolar disorder increased the
      heritability to 37% for the nuclear families. When major depression was added,
      heritability estimates dropped to 34% and 20% for nuclear and extended families,
      respectively. CONCLUSIONS: Endophenotypes and psychotic disorders exhibit
      comparable levels of heritability in the COGS-1 family sample. The ascertainment
      of families with discordant sibpairs to increase endophenotypic contrast may
      underestimate diagnostic heritability relative to other studies. However,
      population-based studies also report significantly lower heritability estimates
      for SZ. Collectively, these findings support the importance of endophenotype
      based strategies and the dimensional view of psychosis.

PMID- 24903416
TI  - Interdisciplinary approaches to the phenomenology of auditory verbal
      hallucinations.
AB  - Despite the recent proliferation of scientific, clinical, and narrative accounts
      of auditory verbal hallucinations (AVHs), the phenomenology of voice hearing
      remains opaque and undertheorized. In this article, we outline an
      interdisciplinary approach to understanding hallucinatory experiences which seeks
      to demonstrate the value of the humanities and social sciences to advancing
      knowledge in clinical research and practice. We argue that an interdisciplinary
      approach to the phenomenology of AVH utilizes rigorous and context-appropriate
      methodologies to analyze a wider range of first-person accounts of AVH at 3
      contextual levels: (1) cultural, social, and historical; (2) experiential; and
      (3) biographical. We go on to show that there are significant potential benefits
      for voice hearers, clinicians, and researchers. These include (1) informing the
      development and refinement of subtypes of hallucinations within and across
      diagnostic categories; (2) "front-loading" research in cognitive neuroscience;
      and (3) suggesting new possibilities for therapeutic intervention. In conclusion,
      we argue that an interdisciplinary approach to the phenomenology of AVH can
      nourish the ethical core of scientific enquiry by challenging its interpretive
      paradigms, and offer voice hearers richer, potentially more empowering ways to
      make sense of their experiences.

PMID- 24903417
TI  - Childhood residential mobility, schizophrenia, and bipolar disorder: a population
      based study in Denmark.
AB  - INTRODUCTION: Childhood adversity is gaining increasing attention as a plausible
      etiological factor in the development of psychotic disorders. Childhood
      residential mobility is a potential risk factor that has received little
      attention in this context. METHODS: We used registry data to estimate
      associations of residential mobility with narrow and broad schizophrenia and
      bipolar disorder across the course of childhood among 1.1 million individuals
      born in Denmark 1971-1991 and followed from age 15 through 2010. We assessed
      effect modification by sex, family history of mental disorder, the presence of
      siblings close in age, and distance moved. RESULTS: In individual-year models
      adjusted for family history, urbanicity at birth, and parental age, mobility at
      all ages except the year of birth was associated with heightened risk of narrow
      and broad schizophrenia, and risk increased with age at moving and with the
      number of moves. Further adjustment for mobility at all ages 0-15 revealed
      associations mainly during the latter half of childhood, which were strongest
      during adolescence. Associations between mobility and bipolar disorder were fewer
      and weaker compared to schizophrenia. There was modest evidence of interaction
      with family history of psychiatric diagnosis, but little evidence for interaction
      by sex, the presence of closely-aged siblings, or distance moved. Schizophrenia
      associations did not appear attributable to increased mobility among adolescents
      with earlier onset. CONCLUSIONS: Mobility may increase risk for psychotic
      disorders, particularly schizophrenia. Children may be especially vulnerable
      during adolescence. Future research should investigate the importance of school
      changes and the potential for interaction with genetic risk.

PMID- 24903419
TI  - Gene set analysis: limitations in popular existing methods and proposed
      improvements.
AB  - MOTIVATION: Gene set analysis is the analysis of a set of genes that collectively
      contribute to a biological process. Most popular gene set analysis methods are
      based on empirical P-value that requires large number of permutations. Despite
      numerous gene set analysis methods developed in the past decade, the most popular
      methods still suffer from serious limitations. RESULTS: We present a gene set
      analysis method (mGSZ) based on Gene Set Z-scoring function (GSZ) and asymptotic
      P-values. Asymptotic P-value calculation requires fewer permutations, and thus
      speeds up the gene set analysis process. We compare the GSZ-scoring function with
      seven popular gene set scoring functions and show that GSZ stands out as the best
      scoring function. In addition, we show improved performance of the GSA method
      when the max-mean statistics is replaced by the GSZ scoring function. We
      demonstrate the importance of both gene and sample permutations by showing the
      consequences in the absence of one or the other. A comparison of asymptotic and
      empirical methods of P-value estimation demonstrates a clear advantage of
      asymptotic P-value over empirical P-value. We show that mGSZ outperforms the
      state-of-the-art methods based on two different evaluations. We compared mGSZ
      results with permutation and rotation tests and show that rotation does not
      improve our asymptotic P-values. We also propose well-known asymptotic
      distribution models for three of the compared methods. AVAILABILITY AND
      IMPLEMENTATION: mGSZ is available as R package from cran.r-project.org.

PMID- 24903418
TI  - SensA: web-based sensitivity analysis of SBML models.
AB  - SUMMARY: SensA is a web-based application for sensitivity analysis of
      mathematical models. The sensitivity analysis is based on metabolic control
      analysis, computing the local, global and time-dependent properties of model
      components. Interactive visualization facilitates interpretation of usually
      complex results. SensA can contribute to the analysis, adjustment and
      understanding of mathematical models for dynamic systems. AVAILABILITY AND
      IMPLEMENTATION: SensA is available at http://gofid.biologie.hu-berlin.de/ and can
      be used with any modern browser. The source code can be found at
      https://bitbucket.org/floettma/sensa/ (MIT license)

PMID- 24903420
TI  - Sushi.R: flexible, quantitative and integrative genomic visualizations for
      publication-quality multi-panel figures.
AB  - MOTIVATION: Interpretation and communication of genomic data require flexible and
      quantitative tools to analyze and visualize diverse data types, and yet, a
      comprehensive tool to display all common genomic data types in publication
      quality figures does not exist to date. To address this shortcoming, we present
      Sushi.R, an R/Bioconductor package that allows flexible integration of genomic
      visualizations into highly customizable, publication-ready, multi-panel figures
      from common genomic data formats including Browser Extensible Data (BED),
      bedGraph and Browser Extensible Data Paired-End (BEDPE). Sushi.R is open source
      and made publicly available through GitHub (https://github.com/dphansti/Sushi)
      and Bioconductor (http://bioconductor.org/packages/release/bioc/html/Sushi.html).

PMID- 24903421
TI  - Improving translation initiation site and stop codon recognition by using more
      than two classes.
AB  - MOTIVATION: The recognition of translation initiation sites and stop codons is a
      fundamental part of any gene recognition program. Currently, the most successful
      methods use powerful classifiers, such as support vector machines with various
      string kernels. These methods all use two classes, one of positive instances and
      another one of negative instances that are constructed using sequences from the
      whole genome. However, the features of the negative sequences differ depending on
      the position of the negative samples in the gene. There are differences depending
      on whether they are from exons, introns, intergenic regions or any other
      functional part of the genome. Thus, the positive class is fairly homogeneous, as
      all its sequences come from the same part of the gene, but the negative class is
      composed of different instances. The classifier suffers from this problem. In
      this article, we propose the training of different classifiers with different
      negative, more homogeneous, classes and the combination of these classifiers for
      improved accuracy. RESULTS: The proposed method achieves better accuracy than the
      best state-of-the-art method, both in terms of the geometric mean of the
      specificity and sensitivity and the area under the receiver operating
      characteristic and precision recall curves. The method is tested on the whole
      human genome. The results for recognizing both translation initiation sites and
      stop codons indicated improvements in the rates of both false-negative results
      (FN) and false-positive results (FP). On an average, for translation initiation
      site recognition, the false-negative ratio was reduced by 30.2% and the FP ratio
      decreased by 10.9%. For stop codon prediction, FP were reduced by 41.4% and FN by
      31.7%. AVAILABILITY AND IMPLEMENTATION: The source code is licensed under the
      General Public License and is thus freely available. The datasets and source code
      can be obtained from http://cib.uco.es/site-recognition. CONTACT:
      npedrajas@uco.es.

PMID- 24903422
TI  - Detection of inter-patient left and right bundle branch block heartbeats in ECG
      using ensemble classifiers.
AB  - BACKGROUND: Left bundle branch block (LBBB) and right bundle branch block (RBBB)
      not only mask electrocardiogram (ECG) changes that reflect diseases but also
      indicate important underlying pathology. The timely detection of LBBB and RBBB is
      critical in the treatment of cardiac diseases. Inter-patient heartbeat
      classification is based on independent training and testing sets to construct and
      evaluate a heartbeat classification system. Therefore, a heartbeat classification
      system with a high performance evaluation possesses a strong predictive
      capability for unknown data. The aim of this study was to propose a method for
      inter-patient classification of heartbeats to accurately detect LBBB and RBBB
      from the normal beat (NORM). METHODS: This study proposed a heartbeat
      classification method through a combination of three different types of
      classifiers: a minimum distance classifier constructed between NORM and LBBB; a
      weighted linear discriminant classifier between NORM and RBBB based on Bayesian
      decision making using posterior probabilities; and a linear support vector
      machine (SVM) between LBBB and RBBB. Each classifier was used with matching
      features to obtain better classification performance. The final types of the test
      heartbeats were determined using a majority voting strategy through the
      combination of class labels from the three classifiers. The optimal parameters
      for the classifiers were selected using cross-validation on the training set. The
      effects of different lead configurations on the classification results were
      assessed, and the performance of these three classifiers was compared for the
      detection of each pair of heartbeat types. RESULTS: The study results showed that
      a two-lead configuration exhibited better classification results compared with a
      single-lead configuration. The construction of a classifier with good performance
      between each pair of heartbeat types significantly improved the heartbeat
      classification performance. The results showed a sensitivity of 91.4% and a
      positive predictive value of 37.3% for LBBB and a sensitivity of 92.8% and a
      positive predictive value of 88.8% for RBBB. CONCLUSIONS: A multi-classifier
      ensemble method was proposed based on inter-patient data and demonstrated a
      satisfactory classification performance. This approach has the potential for
      application in clinical practice to distinguish LBBB and RBBB from NORM of
      unknown patients.

PMID- 24903423
TI  - Hereditary Pheochromocytoma.
AB  - INTRODUCTION: Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare
      neuroendocrine tumors with an estimated occurrence of 2 to 5 patients per million
      per year and an incidence of about 1 per 100 000 in the general population. These
      tumors may arise sporadically or be associated to various syndromes, namely
      multiple endocrine neoplasia type 2, neurofibromatosis type 1, Von Hippel-Lindau
      syndrome, and hereditary paraganglioma-pheochromocytoma syndromes. OBJECTIVES:
      This article aims to review the current epidemiology, pathogenesis, clinical
      presentation, and genetic aspects of syndromes associated with hereditary
      PHEO/PGL. METHODS: The literature research, conducted at PubMed database,
      included review articles, published from February 2009 to February 2014, written
      in English or Portuguese, using as query: "Hereditary AND Pheochromocytoma."
      CONCLUSION: These tumors can be part of a myriad hereditary conditions that are
      not yet fully understood. Nevertheless, important systemic symptoms and even
      fatal outcomes can occur. Knowledge of these hereditary conditions can ensure a
      more efficient detection, treatment, and even prevention of these neuroectodermal
      tumors, thus new tests and studies should be conducted.

PMID- 24903424
TI  - Fabrication of antibody microarrays by light-induced covalent and oriented
      immobilization.
AB  - Antibody microarrays have important applications for the sensitive detection of
      biologically important target molecules and as biosensors for clinical
      applications. Microarrays produced by oriented immobilization of antibodies
      generally have higher antigen-binding capacities than those in which antibodies
      are immobilized with random orientations. Here, we present a UV photo-cross
      linking approach that utilizes boronic acid to achieve oriented immobilization of
      an antibody on a surface while retaining the antigen-binding activity of the
      immobilized antibody. A photoactive boronic acid probe was designed and
      synthesized in which boronic acid provided good affinity and specificity for the
      recognition of glycan chains on the Fc region of the antibody, enabling covalent
      tethering to the antibody upon exposure to UV light. Once irradiated with optimal
      UV exposure (16 mW/cm(2)), significant antibody immobilization on a boronic acid
      presenting surface with maximal antigen detection sensitivity in a single step
      was achieved, thus obviating the necessity of prior antibody modifications. The
      developed approach is highly modular, as demonstrated by its implementation in
      sensitive sandwich immunoassays for the protein analytes Ricinus communis
      agglutinin 120, human prostate-specific antigen, and interleukin-6 with limits of
      detection of 7.4, 29, and 16 pM, respectively. Furthermore, the present system
      enabled the detection of multiple analytes in samples without any noticeable
      cross-reactivities. Antibody coupling via the use of boronic acid and UV light
      represents a practical, oriented immobilization method with significant
      implications for the construction of a large array of immunosensors for
      diagnostic applications. 

PMID- 24903425
TI  - Addiction research centres and the nurturing of creativity: IFT Institut fur
      Therapieforschung in Munich, Germany.
AB  - This paper describes the history and current structure of the Institut fur
      Therapieforschung (IFT) [Institute for Therapy Research] in Munich, as well as
      major research topics and factors which might contribute to a creative structure
      and atmosphere for innovative research in the addiction field. The institute was
      founded in 1973 as a non-profit non-governmental organization (NGO) with a focus
      on applied research. Starting with behaviour therapy-based development and
      evaluation of programmes for alcohol, illicit drugs and smoking and the
      evaluation of treatment services, the institute gradually expanded its topics,
      covering prevention (1985) and epidemiology and policy evaluation (1990), and
      participated throughout this period in the development of guidelines and
      screening, diagnostic and clinical instruments. Later, the IFT tried to bridge
      the gap between basic sciences, applied research, health-care services and health
      policy, with a network of national and international contacts, including its own
      university engagements and collaborations with foreign research groups and
      national and European Union (EU) agencies. Possible creativity-promoting factors
      on the institutional and individual levels are discussed, e.g. the collaboration
      of experienced senior researchers with carefully selected innovative doctoral
      students, considerable in-house and external training of young researchers and
      the early participation and presentation of their work at international
      conferences, independence from stakeholders in the field and the refusal of
      project funds which require external clearance of publications. 

PMID- 24903428
TI  - Editorial: Noncoeliac gluten sensitivity--a disease of the mind or gut?

PMID- 24903426
TI  - Pharmacotherapy for acute mania and disconcordance with treatment guidelines:
      bipolar mania pathway survey (BIPAS) in mainland China.
AB  - BACKGROUND: With the recent attention to evidence-based medicine in psychiatry, a
      number of treatment guidelines for bipolar disorders have been published. This
      survey investigated prescribing patterns and predictors for guideline
      disconcordance in the acute treatment of a manic and mixed episode across
      mainland China. METHODS: The pharmacological treatments of 2828 patients with a
      recent hypomanic/manic episode or mixed state were examined. Guidelines
      disconcordance was determined by comparing the medication(s) patients were
      prescribed with the recommendation(s) in the guidelines of the Canadian Network
      for Mood and Anxiety Treatments. RESULTS: The most common pattern of
      pharmacological treatments for an acute manic or mixed episode was a mood
      stabilizer plus an atypical antipsychotic (n = 1345, 47.6%), and the rate of
      guideline-disconcordant treatments was 11.1%. The patients who were treated in
      general hospitals were more likely to receive guideline-disconcordant treatments
      than those who were treated in psychiatric hospitals, with an OR of 1.84 (95% CI
      1.44-2.36). Similarly, the patients with a mixed episode at study entry were more
      likely to receive guideline-disconcordant treatments than those with a manic
      episode, with an OR of 1.69 (95% CI 1.22-2.35). In contrast, the patients with a
      longer duration of disease (>5 years) were less likely to receive guideline
      disconcordant treatments than those with a short duration, with an OR of 0.47
      (95% CI 0.36-0.60). CONCLUSIONS: In mainland China, the disconcordance with
      treatment guidelines for a most recent acute manic or mixed episode was modest
      under naturalistic conditions. The higher risk for disconcordance in general
      hospitals than in psychiatric hospitals suggests that special education based on
      treatment guidelines to practitioners in general hospitals is necessary in order
      to reduce the risk for disconcordant treatments.

PMID- 24903429
TI  - Editorial: Noncoeliac gluten sensitivity--a disease of the mind or gut? Authors'
      reply.

PMID- 24903430
TI  - Editorial: Anti-viral therapy for prevention of perinatal HBV transmission-
      extending therapy beyond birth and the risk of post-partum flare.

PMID- 24903431
TI  - Editorial: Anti-viral therapy for prevention of perinatal HBV transmission-
      extending therapy beyond birth and the risk of post-partum flare; authors' reply.

PMID- 24903432
TI  - Letter: Persisting clinical symptoms in microscopic colitis in remission.

PMID- 24903433
TI  - Letter: Persisting clinical symptoms in microscopic colitis in remission-
      authors' reply.

PMID- 24903434
TI  - Letter: Faecal microbiota transplantation--not a one-size-fits-all approach;
      authors' reply.

PMID- 24903435
TI  - Letter: Faecal microbiota transplantation--not a one-size-fits-all approach.

PMID- 24903436
TI  - Letter: Limitations of studies to evaluate the significance of anti-tumour
      necrosis factor serum levels in Crohn's disease.

PMID- 24903437
TI  - Letter: Limitations of studies to evaluate the significance of anti-tumour
      necrosis factor serum levels in Crohn's disease--authors' reply.

PMID- 24903439
TI  - p.Y1449C SCN5A mutation associated with overlap disorder comprising conduction
      disease, Brugada syndrome, and atrial flutter.
AB  - Mutations in the SCN5A gene, which encodes the cardiac sodium channel, have been
      associated with cardiac arrhythmia syndromes and conduction disease. Specific
      SCN5A mutations had initially been considered to cause specific phenotypes. More
      recently, some SCN5A mutations have been associated with overlap syndromes,
      characterized by phenotypic heterogeneity within and between mutation carriers.
      Here we report and associate the presence of the p.Y1449C SCN5A mutation in a
      single family with a spectrum of cardiac phenotypes including conduction disease,
      Brugada syndrome and atrial arrhythmias, for the first time to our knowledge. 

PMID- 24903438
TI  - Long-term results in recipients of combined HLA-mismatched kidney and bone marrow
      transplantation without maintenance immunosuppression.
AB  - We report here the long-term results of HLA-mismatched kidney transplantation
      without maintenance immunosuppression (IS) in 10 subjects following combined
      kidney and bone marrow transplantation. All subjects were treated with
      nonmyeloablative conditioning and an 8- to 14-month course of calcineurin
      inhibitor with or without rituximab. All 10 subjects developed transient
      chimerism, and in seven of these, IS was successfully discontinued for 4 or more
      years. Currently, four subjects remain IS free for periods of 4.5-11.4 years,
      while three required reinstitution of IS after 5-8 years due to recurrence of
      original disease or chronic antibody-mediated rejection. Of the 10 renal
      allografts, three failed due to thrombotic microangiopathy or rejection. When
      compared with 21 immunologically similar living donor kidney recipients treated
      with conventional IS, the long-term IS-free survivors developed significantly
      fewer posttransplant complications. Although most recipients treated with none or
      two doses of rituximab developed donor-specific antibody (DSA), no DSA was
      detected in recipients treated with four doses of rituximab. Although further
      revisions of the current conditioning regimen are planned in order to improve
      consistency of the results, this study shows that long-term stable kidney
      allograft survival without maintenance IS can be achieved following transient
      mixed chimerism induction. 

PMID- 24903440
TI  - Tirone David procedure for bicuspid aortic valve disease: impact of root geometry
      and valve type on mid-term outcomes.
AB  - OBJECTIVES: A 180/180 degrees  configuration has been reported to increase repair
      durability after valve-sparing aortic root replacement (V-SARR) for bicuspid
      aortic valve (BAV) disease. We studied the impact of commissural angular
      configuration (CAC) and of BAV type on valve performance after V-SARR. METHODS: A
      total of 85 BAV patients (68 males, age 44 +/- 11 years) underwent Tirone David-V
      V-SARR between 1997 and 2013. BAV type was documented intraoperatively, and CAC
      determined from pre- and postoperative computed tomography scans as the angle
      subtended by the non-fused cusp. Transthoracic echocardiogram was performed at 6
      +/- 3 days and at 2.9 +/- 2.1 years. Functional end-points included freedom from
      aortic regurgitation (AR) 1+, AR 2+ and freedom from AR progression (0 to 1+, or
      1+ to 2+). Tested variables included preoperative CAC (>160 vs <160 degrees ) and
      changes in CAC after V-SARR (Delta > 30 degrees  vs Delta < 30 degrees ) and
      Sievers' BAV type (SO or S1). RESULTS: CAC in SO-BAV (n = 26) changed minimally
      from 164 +/- 12 to 171 +/- 11 degrees  (mean Delta = 7.2 +/- 16 degrees , P =
      0.044), whereas in S1-BAV (n = 59) CAC changed substantially from 132 +/- 19 to
      156 +/- 18 degrees  (mean Delta = 27 +/- 21 degrees , P < 0.001). Larger
      postoperative CAC angles were not linked to better mid-term valve performance,
      but Sievers' BAV type had a major effect on valve performance: mild AR in S1/i
      BAV progressed more often (76 vs 32% at 4 years, P = 0.017) and 1+ AR was more
      frequent (70 vs 36% at 4 years, P = 0.008) compared with SO-BAV. CONCLUSIONS: BAV
      type, including number of raphes, sinuses and commissures (SO superior to S1) but
      not commissure geometry within the neoroot alone, appears to be linked to
      functional outcomes after V-SARR for BAV.

PMID- 24903441
TI  - SF Box--a tool for evaluating the effects on soil functions in remediation
      projects.
AB  - Although remediation is usually aimed at reducing the risks posed by contaminants
      to human health and the environment, it is also desirable that the remediated
      soil within future green spaces is capable of providing relevant ecological
      functions, e.g., basis for primary production. Yet while addressing a
      contamination problem by reducing contaminant concentration and/or amounts in the
      soil, the remedial action itself can lead to soil structure disturbances, decline
      in organic matter and nutrient deficiencies, and in turn affect a soil's capacity
      to carry out its ecological soil functions. This article presents the Soil
      Function Box (SF Box) tool that is aimed to facilitate integration of information
      from suggested soil quality indicators (SQIs) into a management process in
      remediation using a scoring method. The scored SQIs are integrated into a soil
      quality index corresponding to 1 of 5 classes. SF Box is applied to 2 cases from
      Sweden (Kvillebacken and Hexion), explicitly taking into consideration
      uncertainties in the results by means of Monte Carlo simulations. At both sites
      the generated soil quality indices corresponded to a medium soil performance
      (soil class 3) with a high certainty. The main soil constraints at both
      Kvillebacken and Hexion were associated with biological activity in the soil, as
      soil organisms were unable to supply plant-available N. At the Kvillebacken site
      the top layer had a content of coarse fragment (o > 2 mm) higher than 35%,
      indicating plant rooting limitations. At the Hexion site, the soil had limited
      amount of organic matter, thus poor aggregate stability and nutrient cycling
      potential. In contrast, the soil at Kvillebacken was rich in organic matter. The
      soils at both sites were capable of storing a sufficient amount of water for soil
      organisms between precipitation events.

PMID- 24903443
TI  - Pregnancy complications and neonatal outcomes: problems and perspectives.

PMID- 24903444
TI  - Important lessons about ear drainage in preterm infants.

PMID- 24903445
TI  - Mitochondrial DNA and sudden infant death syndrome.

PMID- 24903446
TI  - Four-year-old female with abdominal pain (case presentation).

PMID- 24903447
TI  - Four-year-old female with abdominal pain (discussion and diagnosis).

PMID- 24903448
TI  - Perforation and bacterial contamination of microscope covers in lumbar spinal
      decompressive surgery.
AB  - OBJECTIVE: To determine the integrity of microscope covers and bacterial
      contamination at the end of lumbar spinal decompressive surgery. MATERIALS AND
      METHODS: A prospective study of 25 consecutive lumbar spinal decompressions with
      the use of a surgical microscope was performed. For detection of perforations,
      the microscope covers were filled with water at the end of surgery and the
      presence of water leakage in 3 zones (objective, ocular and control panel) was
      examined. For detection of bacterial contamination, swabs were taken from the
      covers at the same locations before and after surgery. RESULTS: Among the 25
      covers, 1 (4%) perforation was observed and no association between perforation
      and bacterial contamination was seen; 3 (4%) of 75 smears from the 25 covers
      showed post-operative bacterial contamination, i.e. 2 in the ocular zone and 1 in
      the optical zone, without a cover perforation. CONCLUSIONS: The incidence of
      microscope cover perforation was very low and was not shown to be associated with
      bacterial contamination. External sources of bacterial contamination seem to
      outweigh the problem of contamination due to failure of cover integrity.

PMID- 24903449
TI  - Canine hepacivirus and idiopathic hepatitis in dogs from a Dutch cohort.
AB  - Liver diseases are highly prevalent in the general dog population, though the
      etiology is often unknown. Recently a homolog of human hepatitis C virus was
      discovered in dogs with respiratory infections. Although this canine hepacivirus
      (CHV) was detectable in some liver samples, a clear link with liver disease has
      not been established. A recent study by Bexfield et al. showed that in a large
      cohort of dogs from the UK with idiopathic hepatitis, no evidence can be found
      for exposure to, or carrier state of CHV both in liver and in serum. The authors
      however state that 'the absence of CHV infection on dogs from the UK might not
      represent the global ecology of the virus'. We investigated CHV-infection in 267
      liver biopsies from 120 dogs idiopathic hepatitis and 135 control animals, in a
      population from the Netherlands. Using a highly sensitive PCR assay for CHV-NS3,
      no CHV was detected in all 267 liver samples. Our data show that the lack of
      association between canine hepacivirus and chronic liver disease in dogs is not
      limited to the UK, but is also found in an independent cohort from the European
      continent. 

PMID- 24903450
TI  - Chitosan-xanthan gum microparticle-based oral tablet for colon-targeted and
      sustained delivery of quercetin.
AB  - CONTEXT: Quercetin (QUE) is a flavonoid with antioxidant/anti-inflammatory
      properties, poorly absorbed when orally administered. OBJECTIVES: To prepare
      chitosan/xanthan gum microparticles to increase QUE oral bioavailability and
      optimize its release in the colon. MATERIALS AND METHODS: Chitosan/xanthan gum
      hydrogel embedding QUE was spray-dried to obtain microparticles characterized by
      size, scanning electron microscopy, differential scanning calorimetry and X-ray
      diffraction. Microparticles were compressed into tablets, coated with Eudragit(r)
      to further prevent degradation in acidic pH. The swelling degree and QUE release
      in simulated gastric and intestinal pH were investigated. RESULTS: Microparticles
      were smooth and spherical, around 5 um, with successful QUE loading.
      Microparticle tablets provided resistance to acidic conditions, allowing complete
      drug release in alkaline pH, mimicking colonic environment. The release was
      controlled by non-Fickian diffusion of the dissolved drug out of the swollen
      polymeric tablet. DISCUSSION AND CONCLUSION: Microparticle tablets represent a
      promising dosage form for QUE delivery to the colon in the oral therapy of
      inflammatory-based disorders.

PMID- 24903451
TI  - Trichophyton rubrum DNA strain switching increases in patients with onychomycosis
      failing antifungal treatments.
AB  - BACKGROUND: The dermatophyte Trichophyton rubrum is responsible for approximately
      80% of onychomycosis cases. Genetic strain typing was developed to help elucidate
      its epidemiology and pathogenicity. OBJECTIVES: To determine T. rubrum DNA strain
      types in North American patients with onychomycosis and to track the patients
      before and after their course of treatments. METHODS: T. rubrum DNA strain types
      were determined by restriction fragment length polymorphisms in ribosomal DNA and
      Southern blotting from toenails that were cultured from 50 North American
      patients with onychomycosis prior to treatment. Some of the patients were
      subsequently typed from oral terbinafine (n = 6), laser (n = 9) or placebo (n =
      8) treatment groups. Three European DNA strains were obtained for comparison. DNA
      strains from the terbinafine group were tested for in vitro susceptibility to
      terbinafine. RESULTS: Six DNA strain types (A-F) accounted for 94% of T. rubrum
      DNA strains and corresponded to European isolates. Three DNA strains (6%) novel
      to North America were detected. DNA strain type switching occurred in all
      treatment groups: terbinafine (83%), laser (56%) and placebo (25%). Most of the
      switches (50%) observed in the terbinafine group coincided with mycological cures
      followed by relapse. Patients treated with laser therapy or placebo exhibited no
      intermittent cures. DNA strains from the terbinafine group were all susceptible
      to terbinafine in vitro. CONCLUSIONS: Nine T. rubrum DNA strains were identified
      in a North American population: three novel and six predominant to a European
      population. Although DNA strain type switching in onychomycosis is a natural
      phenomenon, with presence in the placebo group, increases following the course of
      failed onychomycosis treatment suggest an antifungal-induced response.

PMID- 24903452
TI  - Early prediction of oral calcium and vitamin D requirements in post-thyroidectomy
      hypocalcaemia.
AB  - OBJECTIVE: To optimize and individualize post-thyroidectomy hypocalcemia
      management. STUDY DESIGN: A multicenter prospective cohort study. SETTING: Two
      tertiary care hospitals. SUBJECTS AND METHODS: parathyroid hormone (PTH) was
      measured preoperatively, then at 1 and 6 hours after surgery. The required doses
      of calcium and vitamin D were defined as those maintaining the patients
      asymptomatic and their cCa >= 2 mmol/L. They were used as an endpoint in a
      generalized linear mixed effect model (GLIMMEX) aiming to identify the best
      predictors of these optimal required doses. Models were evaluated by goodness of
      fit and Receiver Operating Characteristic (ROC) curves. RESULTS: One hundred and
      sixty-eight patients were analyzed; 85.1% were female, 49.3% had BMI > 30, and
      64% had vitamin D deficiency. Post-thyroidectomy hypocalcemia was found in 25.6%,
      of whom 18 (41.9%) were symptomatic and received intravenous calcium. First hour
      percentage of drop in PTH correlated positively with the severity of hypocalcemia
      (P < .0001). The GLIMMIX prediction model for oral calcium requirement was based
      on first-hour percentage change from preoperative PTH level, preoperative actual
      PTH, BMI, and thyroid function. The same predictors were identified for vitamin
      D, except that thyroid function was replaced with vitamin D status. These factors
      were used to build predictive equations for calcium and vitamin D doses.
      CONCLUSION: Our findings help to optimize management of post-thyroidectomy
      hypocalcemia by assisting in the early identification of those who are not at
      risk of hypocalcaemia and by guiding early effective management of those at risk.
      This may reduce complications and medical cost.

PMID- 24903453
TI  - Clinical value of visually identifiable 18F-fluorodeoxyglucose uptake in primary
      papillary thyroid microcarcinoma.
AB  - OBJECTIVE: This study evaluates the relationship between visually identifiable
      (18)F-fluorodeoxyglucose (FDG) uptake in primary papillary thyroid microcarcinoma
      (PTMC) and tumor aggressiveness. STUDY DESIGN: Historical cohort study. SETTING:
      Tertiary care center. METHODS: Clinicopathological factors and PET/CT findings of
      219 PTMC surgical patients who underwent preoperative (18)F-FDG positron emission
      tomography/computed tomography (PET/CT) were retrospectively reviewed. RESULTS:
      (18)F-FDG uptake was observed in the tumors of 124 (56.6%) patients. Tumor size
      (odds ratio [OR] = 1.774; 95% confidence interval [CI], 1.416-2.223; P < .0001)
      and Hashimoto thyroiditis (OR = 2.815; CI, 1.237-6.404; P = .014) independently
      predicted (18)F-FDG uptake. Tumor size (OR = 1.495; CI, 1.217-1.835; P < .0001)
      and BRAF(V600E) mutation (OR = 3.320; CI, 1.056-10.432; P = .040) independently
      predicted extrathyroidal invasion. Multiplicity (OR = 2.375; CI, 1.278-4.415; P =
      .006) independently predicted central lymph node metastasis. CONCLUSION: (18)F
      FDG uptake in PTMC depends on tumor size and Hashimoto thyroiditis. Therefore,
      preoperative PET/CT for PTMC may not help in evaluating tumor aggressiveness.

PMID- 24903454
TI  - Barriers to deferred cord clamping in preterm infants.
AB  - OBJECTIVES: To describe the range of practices employed by units conducting
      deferred cord clamping at very preterm birth. DESIGN: Qualitative study using
      semistructured interviews with neonatal doctors, nurses, midwives, obstetricians
      and managers in a sample of UK maternity units. PARTICIPANTS: 33 neonatal
      doctors, neonatal nurses, midwives, obstetricians and managers. SETTING: UK
      maternity units in 2012. RESULTS: Four key themes emerged. The first concerns the
      variation in guideline content, the absence of a practice of stabilisation with
      cord intact, and issues with implementing and maintaining changes in practice.
      The second concerns the challenges in assessing eligibility. The third concerns
      the competing priorities of delivering the intervention and proceeding with other
      stabilisation manoeuvres and the associated anxiety experienced by professionals.
      The final theme relates to the issue of uncertainty as to optimal treatment
      choices. CONCLUSIONS: The evidence surrounding deferred cord clamping in very
      preterm infants is unclear. This study describes the reported practice of units
      deferring cord clamping in 2012 and will inform trial development.

PMID- 24903455
TI  - Managing the patent ductus arteriosus: current treatment options.
AB  - Optimal management of the patent ductus arteriosus (PDA) in the premature infant
      remains controversial. Despite considerable historical and physiological data
      indicating that a persistent PDA may be harmful, robust evidence of long-term
      benefits or harms from treatment is lacking. This has been equated to a lack of
      benefit but is also a reflection of the fact that most clinical trials were
      designed to assess the effects of short-term (2-8 days) rather than prolonged
      exposure to a PDA. No clinical trials have been designed to assess the effects of
      prolonged exposure of persistent PDA on morbidity and mortality of very premature
      infants in the era of antenatal corticosteroids, surfactant and non-invasive
      respiratory support. Further research is required, but new insights and novel
      therapies are evolving, which will allow greater individual patient assessment,
      understanding of risk and optimisation of treatment. In this paper, we review the
      current literature, evidence for treatment options, including a non
      interventional approach, and research directions for infants <28 weeks'
      gestational age.

PMID- 24903456
TI  - Incidence and predictors of ischemic stroke events during hospitalization in
      patients with transient ischemic attack.
AB  - BACKGROUND: The purpose of this study was to elucidate the incidence and
      predictors of ischemic stroke or recurrent transient ischemic attack (TIA) during
      acute hospitalization in patients with TIA. METHODS: We carried out a multicenter
      retrospective study to clarify the characteristics of in-patients with TIA. The
      subjects of this study were TIA patients admitted to 13 stroke hospitals within 7
      days after onset between 2008 and 2009. TIA was defined as focal neurologic
      symptoms ascribable to a vascular etiology lasting less than 24 h. We
      investigated the incidence and predictors of ischemic events including ischemic
      stroke or recurrent TIA during hospitalization. RESULTS: A total of 464 patients
      with TIA (292 men, 69 +/- 13 years) were registered. Of those, 400 (86.2%) were
      admitted within 24 h of TIA onset. The mean length of hospital stay was 13 days.
      During hospitalization, 8 patients had ischemic strokes and 26 had recurrent
      TIAs. The leading subtype of 8 ischemic strokes was small vessel disease (n = 3)
      followed by cardioembolism (n = 2). Multiple logistic regression analysis showed
      that hypertension (OR: 3.41; 95% CI: 1.23-12.3), MRI-diffusion-weighted image
      positivity (OR: 2.49; 95% CI: 1.15-5.25), and hemiparesis (OR: 2.30; 95% CI: 1.02
      5.88) were independently associated with ischemic events during hospitalization.
      CONCLUSIONS: In this study, 1.7% of patients with TIA had ischemic stroke during
      acute hospitalization, and the most common subtype was small vessel disease.
      Subsequent ischemic stroke and recurrent TIA were associated with hypertension,
      positive DWI findings, and hemiparesis.

PMID- 24903457
TI  - Identification of a genetic variant at 2q12.1 associated with blood pressure in
      East Asians by genome-wide scan including gene-environment interactions.
AB  - BACKGROUND: Genome-wide association studies have identified many genetic loci
      associated with blood pressure (BP). Genetic effects on BP can be altered by
      environmental exposures via multiple biological pathways. Especially, obesity is
      one of important environmental risk factors that can have considerable effect on
      BP and it may interact with genetic factors. Given that, we aimed to test whether
      genetic factors and obesity may jointly influence BP. METHODS: We performed meta
      analyses of genome-wide association data for systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) that included analyses of interaction between
      single nucleotide polymorphisms (SNPs) and the obesity-related anthropometric
      measures, body mass index (BMI), height, weight, and waist/hip ratio (WHR) in
      East-Asians (n = 12,030). RESULTS: We identified that rs13390641 on 2q12.1
      demonstrated significant association with SBP when the interaction between SNPs
      and BMI was considered (P < 5 * 10 -8). The gene located nearest to rs13390641,
      TMEM182, encodes transmembrane protein 182. In stratified analyses, the effect of
      rs13390641 on BP was much stronger in obese individuals (BMI >= 30) than non
      obese individuals and the effect of BMI on BP was strongest in individuals with
      the homozygous A allele of rs13390641. CONCLUSIONS: Our analyses that included
      interactions between SNPs and environmental factors identified a genetic variant
      associated with BP that was overlooked in standard analyses in which only genetic
      factors were included. This result also revealed a potential mechanism that
      integrates genetic factors and obesity related traits in the development of high
      BP.

PMID- 24903458
TI  - Sofie's journey.

PMID- 24903460
TI  - Reflections on living with HIV over time: exploring the perspective of HIV
      infected women over 50.
AB  - OBJECTIVES: Approximately 32.7% of people living with HIV/AIDS (PLWHA) in the USA
      are now over the age of 50. Women comprise a significant percentage of the US HIV
      epidemic and the percentage of women diagnosed with HIV continues to grow;
      however, little is known about women's experiences living and coping with HIV
      over time. The goal of this study was to explore the experiences of US women over
      50 living with HIV to better understand how they make sense of their diagnosis
      and cope with their illness over time and during the aging process. METHOD:
      Nineteen women (mean age = 56.79, SD = 4.63) referred from Boston-area
      organizations and hospitals completed one-time, in-depth individual interviews,
      out of which 47% of the participants were identified as Black/African Americans,
      and 37% as White. The average time since diagnosis was 16.32 years (SD = 5.70).
      Inclusion criteria included: (1) female sex, (2) aged 50 or older, (3) HIV
      diagnosis, and (4) English speaking. Transcribed interviews were analyzed using a
      grounded theory approach and NVivo 9 software. RESULTS: Findings are described
      across the following themes: (1) experiences at diagnosis, (2) uncertainty of
      disease course, (3) acceptance, and (4) living 'well' with HIV. Participants
      appeared to be well adjusted to their HIV diagnosis and described a progression
      to acceptance and survivorship; they identified strategies to 'live well' in the
      context of HIV. For some, health-related uncertainty about the future remained.
      These findings were organized into a model of coping with HIV. CONCLUSION: Themes
      and issues identified by this study may help guide interventions across the
      lifespan for women with HIV.

PMID- 24903459
TI  - Alternative polyadenylation in the nervous system: to what lengths will 3' UTR
      extensions take us?
AB  - Alternative cleavage and polyadenylation (APA) can diversify coding and non
      coding regions, but has particular impact on increasing 3' UTR diversity. Through
      the gain or loss of regulatory elements such as RNA binding protein and microRNA
      sites, APA can influence transcript stability, localization, and translational
      efficiency. Strikingly, the central nervous systems of invertebrate and
      vertebrate species express a broad range of transcript isoforms bearing extended
      3' UTRs. The molecular mechanism that permits proximal 3' end bypass in neurons
      is mysterious, and only beginning to be elucidated. This landscape of neural 3'
      UTR extensions, many reaching unprecedented lengths, may help service the unique
      post-transcriptional regulatory needs of neurons. A combination of approaches,
      including transcriptome-wide profiling, genetic screening to identify APA
      factors, biochemical dissection of alternative 3' end formation, and manipulation
      of individual neural APA targets, will be necessary to gain fuller perspectives
      on the mechanism and biology of neural-specific 3' UTR lengthening. 

PMID- 24903461
TI  - A preliminary study: effects of football training on glucose control, body
      composition, and performance in men with type 2 diabetes.
AB  - The effects of regular football training on glycemic control, body composition,
      and peak oxygen uptake (VO2 peak) were investigated in men with type 2 diabetes
      mellitus (T2DM). Twenty-one middle-aged men (49.8 +/- 1.7 years +/- SEM) with
      T2DM were divided into a football training group (FG; n = 12) and an inactive
      control group (CG; n = 9) during a 24-week intervention period (IP). During a 1-h
      football training session, the distance covered was 4.7 +/- 0.2 km, mean heart
      rate (HR) was 83 +/- 2% of HRmax, and blood lactate levels increased (P < 0.001)
      from 2.1 +/- 0.3 to 8.2 +/- 1.3 mmol/L. In FG, VO2 peak was 11% higher (P <
      0.01), and total fat mass and android fat mass were 1.7 kg and 12.8% lower (P <
      0.001), respectively, after IP. After IP, the reduction in plasma glucose was
      greater (P = 0.02) in FG than the increase in CG, and in FG, GLUT-4 tended to be
      higher (P = 0.072) after IP. For glycosylated hemoglobin (HbA1), an overall time
      effect (P < 0.01) was detected after 24 weeks. After IP, the number of
      capillaries around type I fibers was 7% higher (P < 0.05) in FG and 5% lower (P <
      0.05) in CG. Thus, in men with T2DM, regular football training improves VO2 peak,
      reduces fat mass, and may positively influence glycemic control.

PMID- 24903462
TI  - Association between perceived health care stigmatization and BMI change.
AB  - BACKGROUND/AIMS: This study examined the association between experiences of
      health care stigmatization and BMI changes in men and women with normal weight
      and obesity in Sweden. METHODS: The participants were drawn from a population
      based survey in Sweden (1996-2006), and data on their perceived health care
      stigmatization were measured in 2008. They were categorized in individuals with
      normal weight (n = 1,064), moderate obesity (n = 1,273), and severe obesity (n =
      291). The main outcome measure was change in BMI. RESULTS: Individuals with
      severe obesity experiencing any health care stigmatization showed a BMI increase
      by 1.5 kg/m2 more than individuals with severe obesity with no such experience.
      For individuals with moderate obesity, insulting treatment by a physician and
      avoidance of health care were associated with a relative BMI increase of 0.40 and
      0.75 kg/m2, respectively, compared with their counterparts who did not experience
      stigmatization in these areas. No difference in experience of any form of health
      care stigmatizing associated BMI change was observed for men and women with
      normal weight. CONCLUSION: In this large, population-based study, perceived
      health care stigmatization was associated with an increased relative BMI in
      individuals with severe obesity. For moderate obesity, the evidence of an
      association was inconclusive.

PMID- 24903463
TI  - Support and challenges to the melanosomal casing model based on nanoscale
      distribution of metals within iris melanosomes detected by X-ray fluorescence
      analysis.
AB  - Melanin within melanosomes exists as eumelanin or pheomelanin. Distributions of
      these melanins have been studied extensively within tissues, but less often
      within individual melanosomes. Here, we apply X-ray fluorescence analysis with
      synchrotron radiation to survey the nanoscale distribution of metals within
      purified melanosomes of mice. The study allows a discovery-based characterization
      of melanosomal metals, and, because Cu is specifically associated with eumelanin,
      a hypothesis-based test of the 'casing model' predicting that melanosomes contain
      a pheomelanin core surrounded by a eumelanin shell. Analysis of Cu, Ca, and Zn
      shows variable concentrations and distributions, with Ca/Zn highly correlated,
      and at least three discrete patterns for the distribution of Cu vs. Ca/Zn in
      different melanosomes - including one with a Cu-rich shell surrounding a Ca/Zn
      rich core. Thus, the results support predictions of the casing model, but also
      suggest that in at least some tissues and genetic contexts, other arrangements of
      melanin may co-exist. 

PMID- 24903464
TI  - The design and delivery of a PKA inhibitory polypeptide to treat SCA1.
AB  - Spinocerebellar ataxia-1 (SCA1) is a neurodegenerative disease that primarily
      targets Purkinje cells (PCs) of the cerebellum. The exact mechanism of PC
      degeneration is unknown, however, it is widely believed that mutant ataxin-1
      becomes toxic because of the phosphorylation of its serine 776 (S776) residue by
      cAMP-dependent protein kinase A (PKA). Therefore, to directly modulate mutant
      ATXN1 S776 phosphorylation and aggregation, we designed a therapeutic polypeptide
      to inhibit PKA. This polypeptide comprised of a thermally responsive elastin-like
      peptide (ELP) carrier, which increases peptide half-life, a PKA inhibitory
      peptide (PKI), and a cell-penetrating peptide (Synb1). We observed that our
      therapeutic polypeptide, Synb1-ELP-PKI, inhibited PKA activity at concentrations
      similar to the PKI peptide. Additionally, Synb1-ELP-PKI significantly suppressed
      mutant ATXN1 S776 phosphorylation and intranuclear inclusion formation in cell
      culture. Further, Synb1-ELP-PKI treatment improved SCA1 PC morphology in
      cerebellar slice cultures. Furthermore, the Synb1-ELP peptide carrier crossed the
      blood-brain barrier and localized to the cerebellum via the i.p. or intranasal
      route. Here, we show the intranasal delivery of ELP-based peptides to the brain
      as a novel delivery strategy. We also demonstrate that our therapeutic
      polypeptide has a great potential to target the neurotoxic S776 phosphorylation
      pathway in the SCA1 disease.

PMID- 24903465
TI  - No effect of short-term green tea extract supplementation on metabolism at rest
      or during exercise in the fed state.
AB  - Supplementation with green tea extract (GTE) in animals has been reported to
      induce numerous metabolic adaptations including increased fat oxidation during
      exercise and improved performance. However, data regarding the metabolic and
      physiological effects of GTE during exercise in humans are limited and equivocal.
      PURPOSE: To examine the effects of short-term GTE treatment on resting energy
      expenditure (REE), wholebody substrate utilization during exercise and time trial
      performance. METHODS: Fifteen active men (24 +/- 3 y; VO(2)peak = 48 +/- 7 ml .
      kg . min(-1); BMI = 26 +/- 3 kg . m(2)((-1))) ingested GTE (3x per day = 1,000
      mg/d) or placebo (PLA) for 2 day in a double-blind, crossover design (each
      separated by a 1 week wash-out period). REE was assessed in the fasted state.
      Subjects then ingested a standardized breakfast (~5.0 kcal . kg(-1)) and 90 min
      later performed a 60 min cycling bout at an intensity corresponding to individual
      maximal fat oxidation (44 +/- 11% VO(2)peak), followed by a 250 kJ TT. RESULTS:
      REE, whole-body oxygen consumption (VO2) and substrate oxidation rates during
      steady-state exercise were not different between treatments. However, mean heart
      rate (HR) was lower in GTE vs. PLA (115 +/- 16 vs. 118 +/- 17 beats . min(-1);
      main effect, p = .049). Mixed venous blood [glycerol] was higher during rest and
      exercise after GTE vs. PLA (p = .006, main effect for treatment) but glucose,
      insulin and free-fatty acids were not different. Subsequent time trial
      performance was not different between treatments (GTE = 25:38 +/- 5:32 vs. PLA =
      26:08 +/- 8:13 min; p = .75). CONCLUSION: GTE had minimal effects on whole-body
      substrate metabolism but significantly increased plasma glycerol and lowered
      heart rate during steady-state exercise, suggesting a potential increase in
      lipolysis and a cardiovascular effect that warrants further investigation.

PMID- 24903466
TI  - Secondary or second primary malignancy in the thyroid? metastatic tumors
      suggested clinically: a differential diagnostic task.
AB  - OBJECTIVE: To describe the algorithms employed to explore the suggestion or
      consideration of metastatic malignancy in the thyroid. STUDY DESIGN: Thirty-seven
      cases with a history of malignancy (n = 21) and/or uncommon fine-needle
      aspiration biopsy (FNAB) findings (n = 37) were reviewed and reclassified
      according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).
      RESULTS: The group was heterogeneous in terms of the final histopathology
      results: the suggested metastasis was confirmed in only half of the cases (11/21;
      52.4%). Primary thyroid malignancies were mostly nondifferentiated, medullary, or
      rare. However, 3 papillary carcinomas (the less common variants) were also found.
      Finally, 5 out of 37 cases were surprisingly benign upon histopathological
      investigation (uncommon repair and fibrotizing Hashimoto thyroiditis).
      CONCLUSIONS: The metastatic nature of thyroid gland nodule(s) must be considered
      in cases of generalization of malignancy and/or uncommon FNAB findings. We must
      be as open-minded as possible from the outset. Additional techniques are helpful
      if available - cytoblock and immunocytochemistry can contribute substantially.
      Morphological comparisons with the previous malignancy are recommended whenever
      possible. To avoid overtreatment, cases without precise typing should not be
      classified as TBSRTC diagnostic category VI - malignant, but should remain in
      TBSRTC diagnostic category V - suspicious for malignancy. Repeated FNAB to enable
      additional techniques may be suggested.

PMID- 24903467
TI  - Mechanisms contributing to adverse cardiovascular events in patients with type 2
      diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone
      methyl.
AB  - BACKGROUND: Bardoxolone methyl, an Nrf2-activating and nuclear factor-kappaB
      inhibiting semisynthetic oleanane triterpenoid compound, was evaluated in a phase
      3 trial (BEACON) in patients with type 2 diabetes mellitus (T2DM) and stage 4
      chronic kidney disease (CKD). The trial was terminated because of an increase in
      heart failure events in the bardoxolone methyl group, many of which appeared
      related to fluid retention. Thus, additional analyses were conducted to explain
      these serious adverse events. METHODS: Patients (n = 2,185) were randomized to
      receive once-daily bardoxolone methyl (20 mg) or placebo. Twenty-four-hour urine
      collections were analyzed in a subset of the BEACON population and from a
      separate, open-label pharmacology study in patients with stage 3b/4 CKD and T2DM
      administered 20 mg bardoxolone methyl once daily for 56 consecutive days.
      RESULTS: Bardoxolone-methyl-treated patients in the BEACON substudy had a
      clinically meaningful reduction in urine volume and sodium excretion at week 4
      relative to baseline (p < 0.05), and a separate study revealed that decreased
      sodium excretion and urine output occurred in some patients with stage 4 CKD but
      not those with stage 3b CKD. The clinical phenotype of fluid overload and heart
      failure in BEACON was similar to that observed with endothelin receptor
      antagonists in advanced CKD patients, and preclinical data demonstrate that
      bardoxolone methyl modifies endothelin signaling. CONCLUSIONS: The totality of
      the evidence suggests that through modulation of the endothelin pathway,
      bardoxolone methyl may pharmacologically promote acute sodium and volume
      retention and increase blood pressure in patients with more advanced CKD.

PMID- 24903468
TI  - Prospective evaluation of the routine use of a nasopharyngeal airway (Wendl Tube)
      during endoscopic propofol-based sedation.
AB  - BACKGROUND/AIMS: Insertion of a nasopharyngeal airway (NPA) during endoscopic
      sedation is only recommended in the event of respiratory problems. We evaluated
      the safety and efficacy of routine insertion of an NPA during sedation in
      gastrointestinal (GI) endoscopy. METHODS: Between July 2009 and April 2012,
      patients with colonoscopy or expected longer-lasting or therapeutic upper GI
      endoscopy were pseudo-randomized in a weekly alternating fashion to perform
      sedation (midazolam in combination with propofol) with or without NPA insertion.
      The primary outcome measure was respiratory depression (oxygen saturation <90%).
      Secondary measures included hypotension (systolic blood pressure <90 mm Hg),
      bradycardia (heart rate <40 beats/min) or nasopharyngeal damage after NPA
      insertion. RESULTS: 216 (106 females, mean age 60.7 +/- 9.65 years) were
      enrolled. Colonoscopy was performed in 131 patients and upper endoscopy in 85
      patients. In 105 patients an NPA was used (intervention group). Five (4.7%) of
      those patients showed minor nasopharyngeal injury. Respiratory depression (13.5
      vs. 1.9%, p = 0.002) and hypotension (11 vs. 5%, p = 0.09) occurred more
      frequently in the control than in the intervention group. CONCLUSION: The routine
      placement of an NPA can reduce the frequency of hypoxemic events during
      endoscopic sedation with minor risks for nasopharyngeal injury.

PMID- 24903469
TI  - The Indiana University Cognitive Health Outcomes Investigation of the Comparative
      Effectiveness of dementia screening (CHOICE) study: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Dementia affects over 4 million people in the US and is frequently
      unrecognized and underdiagnosed in primary care. Routine dementia screening in
      primary care is not recommended by the US Preventive Services Task Force due to
      lack of empirical data on the benefits and harms of screening. This trial seeks
      to fill this gap and contribute information about the benefits, harms, and costs
      of routine screening for dementia in primary care. METHODS/DESIGN: Single
      blinded, parallel, randomized controlled clinical trial with 1:1 allocation. A
      total of 4,000 individuals aged >=65 years without a diagnosis of dementia,
      cognitive impairment, or serious mental illness receiving care at primary care
      practices within two cities in Indiana. Subjects will be randomized to either i)
      screening for dementia using the Memory Impairment Screen Telephone version or
      ii) no screening for dementia. Subjects who screen positive for dementia will be
      referred to the local Aging Brain Care program that delivers an evidence-based
      collaborative care model for dementia and depression. Research assistants will
      administer the 15-item Health Utility Index, Patient Health Questionnaire,
      Generalized Anxiety Disorder Scale, and Medical Outcomes Study at baseline, 1, 6,
      and 12 months. Information about advanced care planning will be collected at
      baseline and 12 months. All enrollees' medical records will be reviewed to
      collect data on health care utilization and costs. DISCUSSION: We have two
      primary hypotheses; first, in comparison to non-screened subjects, those who are
      screened and referred to a dementia collaborative care program will have a higher
      health-related quality of life as measured by the Health Utility Index at 12
      months post-screening. Second, in comparison to non-screened subjects, those who
      are screened and referred to a dementia collaborative care program will not have
      higher depression or anxiety at one month post-screening as measured by the
      Patient Health Questionnaire and Generalized Anxiety Disorder Scale scales. Our
      secondary hypothesis is that screened subjects will have an Incremental Cost
      Effectiveness Ratio below the maximum acceptable threshold of $60,000 per quality
      adjusted life year saved at 12 months. TRIAL REGISTRATION: Ongoing; registered on
      September 19, 2012. ClinicalTrials.gov Identifier: 2012 NCT01699503.

PMID- 24903470
TI  - Visceral leishmaniasis with cutaneous symptoms in a patient treated with
      infliximab followed by fatal consequences.
AB  - Leishmaniasis is an infectious disease caused by parasitic flagellates of the
      genus Leishmania. The authors present a case of 44-year-old man with Crohn's
      disease treated successfully with infliximab. This case report shows rare
      visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient.
      Skin manifestations may occur before or after the visceral infection and they are
      often diverse. 

PMID- 24903471
TI  - Electrochemotherapy: an effective local treatment of cutaneous and subcutaneous
      melanoma metastases.
AB  - Treatment of multiple cutaneous and subcutaneous melanoma metastases is still
      represents a therapeutic challenge for both dermatologists and oncologists.
      Electrochemotherapy (ECT) is a promising therapeutic procedure, owing to its
      ability to improve the penetration of cytotoxic drugs into cancer cells by
      application of current electric pulses. The aim of our study is to evaluate
      efficacy, tolerability and long-term efficacy of ECT in the treatment of advanced
      metastatic melanoma. Thirty patients affected by a total of 654 cutaneous and
      subcutaneous melanoma metastatic nodules were recruited. All patients were
      treated after they had undergone to a mild general anesthesia. Intravenous
      Bleomicina solution was administered 8 minutes before the application of electric
      pulses, generated by a Cliniporator (TM) (the device validated for ECT). The
      objective response rate of 100% (67.28% complete response and 32.72% partial
      response) was observed. A total of 214 metastatic lesions from 24 patients
      received a second ECT session, among them 141 showed a further complete response.
      Twenty-four months later, the local tumor control rate was 72%. The results of
      this study seem to demonstrate that ECT is an effective and valid therapeutic
      tool for the treatment of cutaneous metastases from melanoma. ECT can be
      considered a first-line palliative treatment since it is able to alleviate pain
      and reduce the tumor's spontaneous bleeding with a significant improve of
      patients' quality of life. 

PMID- 24903472
TI  - A case of linear atrophoderma of Moulin successfully treated with methotrexate.
AB  - Linear atrophoderma of Moulin is an acquired rare and self-limited skin
      condition. It is characterized by atrophic bandlike skin lesions that often show
      hyperpigmentation and always follow the lines of Blaschko. Usually it begins in
      childhood or adolescence and there is no evidence of any long term progression.
      We describe a case of a 21-year-old woman with clinical and histological features
      of linear atrophoderma of Moulin. The patient was successfully treated with
      methotrexate 20 mg/week during 6 months with an improvement of skin pigmentation
      and atrophy. Approximately, 30 cases of linear atrophoderma of Moulin were
      described in the literature. There is not a proven effective treatment of this
      dermatosis. High dose penicillin, topical corticosteroids, heparin, and oral
      potassium aminobenzoate have been used but found to be uneffective. To our
      knowledge, this is the first case of extensive linear atrophoderma of Moulin
      treated with methotrexate. 

PMID- 24903473
TI  - Pharmacokinetic/pharmacodynamic evaluation of marbofloxacin in the treatment of
      Haemophilus parasuis and Actinobacillus pleuropneumoniae infections in nursery
      and fattener pigs using Monte Carlo simulations.
AB  - This study evaluated the theoretical clinical outcome of three marbofloxacin
      posology regimens in two groups of pigs (weaners and fatteners) for the treatment
      of Actinobacillus pleuropneumoniae (App) and Haemophilus parasuis (Hp) infection
      and the appearance of resistant bacteria due to the antibiotic treatment. The
      probability of target attainment (PTA) for pharmacokinetic/pharmacodynamics
      (PK/PD) ratios associated with clinical efficacy and with the appearance of
      antimicrobial resistance for fluoroquinolones at each minimum inhibitory
      concentration (MIC) or mutant prevention concentration (MPC) were calculated,
      respectively. The cumulative fraction of response (CFR) was calculated for the
      three posology regimens against App and they ranged from 91.12% to 96.37% in
      weaners and from 93% to 97.43% in fatteners, respectively. In the case of Hp,
      they ranged from 80.52% to 85.14% in weaners and from 82.01% to 88.49% in
      fatteners, respectively. Regarding the PTA of the PK/PD threshold associated with
      the appearance of antimicrobial resistance, results showed that marbofloxacin
      would prevent resistances in most of the animals up to the MPC value of 1 MUg/mL.

PMID- 24903474
TI  - Hole induced Jahn Teller distortion ensuing ferromagnetism in Mn-MgO: bulk,
      surface and one dimensional structures.
AB  - Using density functional theory, we investigate the magnetic properties of Mn
      doped MgO in its bulk (3D), surface (2D) and one dimensional (1D) structures. At
      a low dilute limit (1.5 %), the Mn impurity behaves indifferent to its position
      in 3D but energetically prefers to be on one of the surfaces of 2D and 1D
      structures. At a higher dilute limit (3.1 %), the Mn impurities stabilizing at
      MN(d)((3+)) ionic states prefer to be in a close configuration (4.2 A compared to
      5.95 A) and the antiferromagnetic ordering (AFM) between them is preferred over
      the ferromagnetic ordering. The n-type extrinsic defects (O vacancy), when
      introduced to Mn doped MgO structures, also result in similar AFM exchanges as
      between the Mn impurities. However, the p-type defects (Mg vacancy) in the Mn
      doped MgO structures result in a reduced magnetic moment for the Mn atoms and
      bring a significant Jahn Teller (JT)-type of distortion to the eg and t2g
      degenerate states of MN(d)((3+)) ions. The strong hybridization between distorted
      Mnd states and O2p states results in a FM exchange coupling between the Mn ions,
      in all the three mentioned Mn doped MgO structures. As we move from 3D to 2D, to
      1D structures, the influence of JT distortion decreases, reflecting a decreasing
      trend for the strength of the FM exchange coupling between the Mn atoms.

PMID- 24903475
TI  - Investigation of acoustic streaming patterns around oscillating sharp edges.
AB  - Oscillating sharp edges have been employed to achieve rapid and homogeneous
      mixing in microchannels using acoustic streaming. Here, we used a perturbation
      approach to study the flow around oscillating sharp edges in a microchannel. This
      work extends prior experimental studies to numerically characterize the effect of
      various parameters on the acoustically induced flow. Our numerical results match
      well with the experimental results. We investigated multiple device parameters
      such as the tip angle, oscillation amplitude, and channel dimensions. Our results
      indicate that, due to the inherent nonlinearity of acoustic streaming, the
      channel dimensions could significantly impact the flow patterns and device
      performance. 

PMID- 24903476
TI  - [Diagnosis of inherited diseases of platelet function. Interdisciplinary S2K
      guideline of the Permanent Paediatric Committee of the Society of Thrombosis and
      Haemostasis Research (GTH e. V.)].
AB  - Congenital disorders of platelet function are a heterogeneous group of disorders
      that are often not detected until bleeding occurs. In clinical settings only a
      few methods have proven to be useful for identification and classification of
      inherited platelet disorders. For a rational diagnostic approach, a stepwise
      algorithm is recommended. Patient history and clinical investigation are
      mandatory. Von Willebrand disease and other coagulation disorders should always
      be ruled out prior to specific platelet testing. Platelet count, size, volume
      (MPV) and morphology may guide further investigations. The PFA-100(r) CT is
      suited for screening for severe platelet defects. Platelet aggregometry allows
      assessment of multiple aspects of platelet function. Flow cytometry enables
      diagnosis of thrombasthenia Glanzmann, Bernard-Soulier syndrome and storage pool
      defects. Molecular genetics may confirm a putative diagnosis or pave the way for
      identifying new defects. We present an unabridged version of the
      interdisciplinary guideline. 

PMID- 24903477
TI  - Biocompatible, chimeric peptide-condensed supramolecular nanoparticles for tumor
      cell-specific siRNA delivery and gene silencing.
AB  - Chimeric peptides composed of arginine-rich RNA-binding and tumor cell-targeting
      motifs have been employed to condense siRNA to form supramolecular nanoparticles
      via electrostatic associations and deliver siRNA agents in a tumor cell-specific
      manner. 

PMID- 24903478
TI  - Enhanced generation of cord blood hematopoietic stem and progenitor cells by
      culture with StemRegenin1 and Delta1(Ext-IgG.).

PMID- 24903479
TI  - Effects of the small-molecule inhibitor of integrin alpha4, TBC3486, on pre-B-ALL
      cells.

PMID- 24903480
TI  - Bispecific antibodies targeting tumor-associated antigens and neutralizing
      complement regulators increase the efficacy of antibody-based immunotherapy in
      mice.
AB  - The efficacy of antibody-based immunotherapy is due to the activation of
      apoptosis, the engagement of antibody-dependent cellular cytotoxicity and
      complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance
      CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and
      CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were
      designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59.
      Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti
      CD20 recombinant antibody in cell lines or cells isolated from patients with
      chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluated in
      a human-SCID model of Burkitt lymphoma. The distribution profile of bsAbs mimics
      the data obtained by studying the pharmacokinetics of anti-CD20 antibodies,
      showing a peak in the tumor mass 3-4 days after injection. The treatment with
      bsAbs completely prevented the development of human/SCID lymphoma. The tumor
      growth was blocked by the activation of the C cascade and by the recruitment of
      macrophages, polymorphonuclear and natural killer cells. This strategy can easily
      be applied to the other anti-tumor C-fixing antibodies currently used in the
      clinic or tested in preclinical studies using the same vector with the
      appropriate modifications. 

PMID- 24903481
TI  - MYD88 (L265P) mutation is an independent prognostic factor for outcome in
      patients with diffuse large B-cell lymphoma.

PMID- 24903482
TI  - Survivin modulates genes with divergent molecular functions and regulates
      proliferation of hematopoietic stem cells through Evi-1.
AB  - The inhibitor of apoptosis protein Survivin regulates hematopoiesis, although its
      mechanisms of regulation of hematopoietic stem cells (HSCs) remain largely
      unknown. While investigating conditional Survivin deletion in mice, we found that
      Survivin was highly expressed in phenotypically defined HSCs, and Survivin
      deletion in mice resulted in significantly reduced total marrow HSCs and
      hematopoietic progenitor cells. Transcriptional analysis of Survivin(-/-) HSCs
      revealed altered expression of multiple genes not previously linked to Survivin
      activity. In particular, Survivin deletion significantly reduced expression of
      the Evi-1 transcription factor indispensable for HSC function, and the downstream
      Evi-1 target genes Gata2, Pbx1 and Sall2. The loss of HSCs following Survivin
      deletion and impaired long-term HSC repopulating function could be partially
      rescued by ectopic Evi-1 expression in Survivin -/- HSCs. These data demonstrate
      that Survivin partially regulates HSC function by modulating the Evi-1
      transcription factor and its downstream targets and identify new genetic pathways
      in HSCs regulated by Survivin. 

PMID- 24903483
TI  - Deep renal ectopia causing sciatic mononeuropathy.
AB  - INTRODUCTION: Sciatic mononeuropathy resulting from compression by an adjacent
      pelvic ectopic kidney has not been reported in the literature. Here, the authors
      present a case of a patient presenting with unilateral lower extremity
      paresthesia correlating to the sciatic nerve distribution. RESULTS: MRI
      examination demonstrated lumbosacral plexus compression by a very unusual deeply
      situated renal ectopia. Physicians should consider other rare causes of
      mechanical lumbosacral plexus compression in patients with sciatic
      symptomatology.

PMID- 24903484
TI  - Reduction cranioplasty for macrocephaly with long-standing hydrocephalus and non
      fused fontanelle in Chiari malformation type I.
AB  - INTRODUCTION: Because hydrocephalus is diagnosed and treated at an early stage in
      pediatric patients, pediatric neurosurgeons rarely encounter patients with
      hydrocephalic macrocephaly. There are even fewer cases of infants with long
      standing hydrocephalus in whom macrocephaly progresses and is accompanied by
      skull defect due to malunion of suture lines despite long-term CSF diversion
      treatment. CASE REPORT: We report the case of a male infant with Chiari
      malformation type I who presented with congenital hydrocephalus and occipital
      encephalocele that progressed to hydrocephalic macrocephaly with frontal skull
      defect, despite numerous cerebrospinal fluid diversion operations. The patient
      eventually recovered successfully after reduction cranioplasty.

PMID- 24903485
TI  - A rare immature teratoma of the tela chorioidea of the third ventricle: late
      onset, intrapartum ultrasound diagnosis and postnatal outcome.
AB  - We describe a previously unreported case of immature teratoma originating from
      the tela chorioidea of the third ventricle diagnosed during labor at term of
      pregnancy. Postnatal MR imaging and pediatric neurosurgery with postnatal outcome
      at 6 months of age are reported.

PMID- 24903486
TI  - The carbon cycle and hurricanes in the United States between 1900 and 2011.
AB  - Hurricanes cause severe impacts on forest ecosystems in the United States. These
      events can substantially alter the carbon biogeochemical cycle at local to
      regional scales. We selected all tropical storms and more severe events that made
      U.S. landfall between 1900 and 2011 and used hurricane best track database, a
      meteorological model (HURRECON), National Land Cover Database (NLCD), U. S.
      Department of Agirculture Forest Service biomass dataset, and pre- and post-MODIS
      data to quantify individual event and annual biomass mortality. Our estimates
      show an average of 18.2 TgC/yr of live biomass mortality for 1900-2011 in the US
      with strong spatial and inter-annual variability. Results show Hurricane Camille
      in 1969 caused the highest aboveground biomass mortality with 59.5 TgC. Similarly
      1954 had the highest annual mortality with 68.4 TgC attributed to landfalling
      hurricanes. The results presented are deemed useful to further investigate
      historical events, and the methods outlined are potentially beneficial to
      quantify biomass loss in future events. 

PMID- 24903488
TI  - Identification of CNGA3 mutations in 46 families: common cause of achromatopsia
      and cone-rod dystrophies in Chinese patients.
AB  - IMPORTANCE: Mutations in CNGA3 are the most common cause of achromatopsia and
      cone-rod dystrophies. OBJECTIVE: To identify CNGA3 mutations in patients with
      cone dystrophies or Leber congenital amaurosis. DESIGN, SETTING, AND
      PARTICIPANTS: Clinical data and genomic DNA in 267 Chinese probands from 138
      families with cone dystrophies and 129 families with Leber congenital amaurosis
      collected at the Zhongshan Ophthalmic Center, Guangzhou, China. MAIN OUTCOMES AND
      MEASURES: Variants in CNGA3 and associated phenotypes, assessed by Sanger
      sequencing of CNGA3, bioinformatics of variants, and segregation analysis.
      RESULTS: Homozygous or compound heterozygous mutations in CNGA3, including 26
      novel and 13 known mutations, were identified in 46 probands from 138 families
      with cone dystrophies, but none were found in any of the probands from 129
      families with Leber congenital amaurosis. The 46 probands with CNGA3 mutations
      could be further classified as likely having achromatopsia (18 probands) and cone
      rod dystrophies (28 probands) based on electroretinographic recordings. Analysis
      of family members in 17 of 46 families demonstrated good segregation of the
      disease with the CNGA3 mutations. CONCLUSIONS AND RELEVANCE: To our knowledge,
      this study is the first systemic analysis of CNGA3 in Chinese patients and
      expands the mutational spectrum and associated phenotypes. Our results suggest
      that CNGA3 mutations are a common cause of cone-rod dystrophies and achromatopsia
      in the Chinese population. These data indicate that CNGA3-associated cone
      dystrophies may be a common form of early-onset severe retinal dystrophies.
      Therapeutic potential such as gene therapy targeting this gene may benefit some
      children with early-onset severe retinal dystrophies.

PMID- 24903487
TI  - Amphiphilic macromolecules on cell membranes: from protective layers to
      controlled permeabilization.
AB  - Antimicrobial and cell-penetrating peptides have inspired developments of abiotic
      membrane-active polymers that can coat, penetrate, or break lipid bilayers in
      model systems. Application to cell cultures is more recent, but remarkable
      bioactivities are already reported. Synthetic polymer chains were tailored to
      achieve (i) high biocide efficiencies, and selectivity for bacteria (Gram
      positive/Gram-negative or bacterial/mammalian membranes), (ii) stable and mild
      encapsulation of viable isolated cells to escape immune systems, (iii) pH-,
      temperature-, or light-triggered interaction with cells. This review illustrates
      these recent achievements highlighting the use of abiotic polymers, and compares
      the major structural determinants that control efficiency of polymers and
      peptides. Charge density, sp. of cationic and guanidinium side groups, and
      hydrophobicity (including polarity of stimuli-responsive moieties) guide the
      design of new copolymers for the handling of cell membranes. While polycationic
      chains are generally used as biocidal or hemolytic agents, anionic amphiphilic
      polymers, including Amphipols, are particularly prone to mild permeabilization
      and/or intracell delivery. 

PMID- 24903490
TI  - Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer.
AB  - Angiopoietin-like (ANGPTL) proteins are secreted proteins showing structural
      similarity to members of the angiopoietin family. Some ANGPTL proteins possess
      pleiotropic activities, being involved in cancer lipid, glucose energy
      metabolisms, and angiogenesis. ANGPTL7 is the less characterized member of the
      family whose functional role is only marginally known. In this study, we provide
      experimental evidences that ANGPTL7 is over-expressed in different human cancers.
      To understand the role played by ANGPTL7 in tumor biology, we asked whether
      ANGPTL7 is endogenously expressed by malignant cells or in response to
      environmental stimuli. We found that ANGPTL7 is marginally expressed under
      standard growth condition while it is specifically up-regulated by hypoxia.
      Interestingly, the protein is secreted and partially associated with the exosomal
      fraction, suggesting that it could be found in the systemic circulation of
      oncologic patients and act in an endocrine way. Moreover, we found that ANGPTL7
      exerts a pro-angiogenetic effect on human differentiated endothelial cells by
      stimulating their proliferation, motility, invasiveness, and capability to form
      capillary-like networks while it does not stimulate progenitor endothelial cells.
      Finally, we showed that ANGPTL7 promotes vascularization in vivo in the mouse
      Matrigel sponge assay, thereby accrediting this molecule as a pro-angiogenic
      factor.

PMID- 24903489
TI  - Cardiac stem cell therapy for cardiac repair.
AB  - OPINION STATEMENT: The discovery of adult cardiac stem cells (CSCs) and their
      potential to restore functional cardiac tissue has fueled unprecedented interest
      in recent years. Indeed, stem-cell-based therapies have the potential to
      transform the treatment and prognosis of heart failure, for they have the
      potential to eliminate the underlying cause of the disease by reconstituting the
      damaged heart with functional cardiac cells. Over the last decade, several
      independent laboratories have demonstrated the utility of c-kit+/Lin- resident
      CSCs in alleviating left ventricular dysfunction and remodeling in animal models
      of acute and chronic myocardial infarction. Recently, the first clinical trial of
      autologous CSCs for treatment of heart failure resulting from ischemic heart
      disease (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO])
      has been conducted, and the interim results are quite promising. In this phase I
      trial, no adverse effects attributable to the CSC treatment have been noted, and
      CSC-treated patients showed a significant improvement in ejection fraction at 1
      year (+13.7 absolute units versus baseline), accompanied by a 30.2 % reduction in
      infarct size. Moreover, the CSC-induced enhancement in cardiac structure and
      function was associated with a significant improvement in the New York Heart
      Association (NYHA) functional class and in the quality of life, as measured by
      the Minnesota Living with Heart failure Questionnaire. These results are exciting
      and warrant larger, phase II studies. However, CSC therapy for cardiac repair is
      still in its infancy, and many hurdles need to be overcome to further enhance the
      therapeutic efficacy of CSCs.

PMID- 24903491
TI  - Differences in observers' and teachers' fidelity assessments.
AB  - As evidence-based programs become disseminated, understanding the degree to which
      they are implemented with fidelity is crucial. This study tested the validity of
      fidelity ratings made by observers versus those made by teachers. We hypothesized
      that teachers' reports about fidelity would have a positivity bias when compared
      to observers' reports. Further, we hypothesized that there would generally be low
      correspondence between teachers' and observers' ratings of fidelity. We examined
      teachers' and observers' ratings as they were related to mediating variables
      targeted for change by the intervention. Finally, we examined the role that years
      of teaching experience played in achieving fidelity. Eighteen teachers and four
      research assistants participated in this project as raters. Teachers made video
      recordings of their implementation of All Stars and completed fidelity assessment
      forms. Trained observers independently completed parallel forms for 215 sampled
      classroom sessions. Both teachers and observers rated adherence, quality of
      delivery, attendance, and participant engagement. Teachers made more positive
      fidelity ratings than did observers. With the exception of ratings for
      attendance, teachers and observers failed to agree on fidelity ratings.
      Observers' ratings were significantly related to students' pretest assessments of
      targeted program mediators. That observers' ratings were related to students'
      pretest scores, suggests it is easier to teach well when students are predisposed
      to program success. Teachers' ratings were infrequently related to mediators, but
      when they were, the relationship was counterintuitive. Experienced teachers
      taught with greater fidelity than novice teachers. While possibly inflated and
      inaccurate, gathering fidelity assessments from teachers may sensitize them to
      issues of fidelity as a result of requiring form completion. Assessing fidelity
      through observers' ratings of video recordings has significant merit. As a
      longterm investment in improving prevention outcomes, policy makers should
      consider requiring both teacher and observer fidelity assessments as essential
      components of evaluation. 

PMID- 24903492
TI  - A French description of German psychology laboratories in 1893 by Victor Henri, a
      collaborator of Binet.
AB  - There is a rich tradition of writings about the foundation of psychology
      laboratories, particularly in the United States but also in France. Various
      documents exist concerning former German laboratories in American and French
      literature. But the most interesting French paper was certainly written by a
      young psychologist named Victor Henri (1872-1940) who was a close collaborator of
      Alfred Binet (1857-1911) in the 1890s. Visiting various psychology laboratories,
      he wrote, in 1893, a clear description of the laboratories of Wundt, G. E.
      Muller, Martius and Ebbinghaus. An English translation is given of Henri's paper
      and the historical importance of his contribution is here expounded by
      contrasting the German and French psychologies of the time. 

PMID- 24903494
TI  - Validation of threshold method for myocardial control database by use of clinical
      data.
AB  - A database is an important factor in the statistical analysis of myocardial
      scintigraphy. Our aim in this study was to verify the validity of the threshold
      method using phantoms and to create a clinical database using this method. Since
      this method involves artificially excluding a low count area on a polar map, we
      created a myocardial phantom with defects. Then, we applied this method to the
      construction of a control database (CDB) for which we used stress-rest scans of
      152 male and 52 female Japanese patients. The clinical relevance of this database
      was investigated by comparison of the values between the CDB and a Japanese
      normal database. In the study evaluation, we mainly used the summed extent score
      (SES) and a severity map (severity). Data from the phantom with defects
      demonstrated that the threshold method could compensate for defective areas,
      enabling the use of data for the creation of the CDB. Comparison of the CDB with
      the Japanese normal database showed a good relationship with respect to the SES
      and severity (Initial post-stress: SES: r = 0.978; severity: r = 0.997,
      Redistribution: SES: r = 0.944; severity: r = 0.993). The threshold method
      facilitates the effective creation of a database by use of clinical data. This
      enables individual institutions to build their own databases, taking into account
      differences in collection and processing conditions between institutions as well
      as the characteristics of individual equipment.

PMID- 24903493
TI  - Response to period shifts in tapping and circle drawing: a window into event and
      emergent components of continuous movement.
AB  - Synchronization of movement to a metronome is a well-studied task for both
      discretely and smoothly produced rhythmic movement. In particular, behavioral
      responses to unexpected changes in a regular metronome can reveal both the
      strength and the completeness of error correction mechanisms and temporal
      control. Clock-like control is exhibited by discretely produced movement and
      movement with discrete perceptual information, whereas smoothly produced movement
      does not rely on internal clock mechanisms. Documented differences in error
      correction between discretely and smoothly produced movements have been
      attributed to this different underlying control. In this study, error correction
      mechanisms were examined by inducing changes in the pace of rhythmic movement. An
      overshoot response following the pace change for both tapping and circle drawing
      is documented, and suggests the presence of phase and period correction in both
      tasks. The presence of phase correction in circle drawing also suggests that
      clock and non-clock timing may co-exist within the same movement. Furthermore, a
      sub-group of participants emerged who appropriately changed pace, but were not
      able to correct the phasing of their movement while performing the circle drawing
      task, supporting that phase and period maintenance in timing are independently
      controlled processes. 

PMID- 24903495
TI  - Vascular smooth muscle cells and monocyte-macrophages accomplice in the
      accelerated atherosclerosis of insulin resistance states.

PMID- 24903496
TI  - High-density lipoprotein, beta cells, and diabetes .
AB  - High-density lipoproteins (HDLs) exert a series of potentially beneficial effects
      on many cell types including anti-atherogenic actions on the endothelium and
      macrophage foam cells. HDLs may also exert anti-diabetogenic functions on the
      beta cells of the endocrine pancreas, notably by potently inhibiting stress
      induced cell death and enhancing glucose-stimulated insulin secretion. HDLs have
      also been found to stimulate insulin-dependent and insulin-independent glucose
      uptake into skeletal muscle, adipose tissue, and liver. These experimental
      findings and the inverse association of HDL-cholesterol levels with the risk of
      diabetes development have generated the notion that appropriate HDL levels and
      functionality must be maintained in humans to diminish the risks of developing
      diabetes. In this article, we review our knowledge on the beneficial effects of
      HDLs in pancreatic beta cells and how these effects are mediated. We discuss the
      capacity of HDLs to modulate endoplasmic reticulum stress and how this affects
      beta-cell survival. We also point out the gaps in our understanding on the
      signalling properties of HDLs in beta cells. Hopefully, this review will foster
      the interest of scientists in working on beta cells and diabetes to better define
      the cellular pathways activated by HDLs in beta cells. Such knowledge will be of
      importance to design therapeutic tools to preserve the proper functioning of the
      insulin-secreting cells in our body. 

PMID- 24903498
TI  - [Interdisciplinary treatment of osteosarcomas].

PMID- 24903497
TI  - Modulation of neointimal lesion formation by endogenous androgens is independent
      of vascular androgen receptor.
AB  - AIMS: Low androgen levels have been linked with an increased risk of
      cardiovascular disease in men. Previous studies have suggested that androgens
      directly inhibit atherosclerotic lesion formation although the underlying
      mechanisms for this remain unclear. This study addressed the hypothesis that
      endogenous androgens inhibit arterial remodelling by a direct action on the
      androgen receptor (AR) in the vascular wall. METHODS AND RESULTS: We studied a
      series of novel mouse lines with cell-specific deletion of the AR in either the
      endothelium or in smooth muscle cells or both cell types. Findings were compared
      with a model of global androgen deficiency in wild-type mice (castrated). We
      characterized the cardiovascular phenotype, vascular pharmacology and histology,
      and assessed neointimal lesion formation following vascular injury to the femoral
      artery. Cell-specific AR deletion did not alter body weight, circulating
      testosterone levels or seminal vesicle weight, but caused limited alterations in
      arterial contractility and blood pressure. Neointimal lesion formation was
      unaltered by selective deletion of AR from the vascular endothelium, smooth
      muscle, or both cell types. Castration in wild-type mice increased neointimal
      lesion volume (Sham vs. Castration: 2.4 * 10(7) +/- 4.5 * 10(6) vs. 3.9 * 10(7)
      +/- 4.9 * 10(6) um(3), P = 0.04, n = 9-10). CONCLUSION: Vascular cell-specific AR
      deletion had no effect on neointimal lesion formation, while low systemic
      androgen levels adversely affect neointimal lesion size. These findings suggest
      that the cardio-protective effects of androgens are mediated either by AR outside
      the vasculature or by AR-independent mechanisms.

PMID- 24903499
TI  - [Imaging diagnostics of bone sarcomas].
AB  - BACKGROUND: Bone tumors and especially bone sarcomas are rare lesions of the
      skeletal system in comparison to the much more frequently occurring bone
      metastases. Despite the relative rarity they are important differential diagnoses
      of bone lesions. OBJECTIVE: The aim of this article is to give the reader an
      insight into the fundamentals of the primary imaging of bone sarcomas and to
      illustrate this with the help of two examples (e.g. osteosarcoma and
      chondrosarcoma). RESULTS: The foundation of the imaging of bone sarcomas is the
      radiograph in two planes. This method delivers important information on bone
      tumors. This information should be analyzed with the help of the Lodwick
      classification, the configuration of periosteal reactions and a possible reaction
      of the cortex. A possible tumor matrix and the localization within the skeleton
      or within long bones also provide important information for differential
      diagnostic delimitation. Magnetic resonance imaging (MRI) with specific adapted
      bone tumor sequences allows an exact local staging of a bone sarcoma. In addition
      to local imaging a compartmental MRI which illustrates the entire extent of tumor
      bearing bone and the adjacent joints should be performed to rule out possible
      skip lesions. The most common distant metastases of osteosarcoma and
      chondrosarcoma occur in the lungs; therefore, a computed tomography (CT) of the
      chest is part of staging. Other imaging methods, such as CT of the tumor,
      positron emission tomography CT (PET-CT), bone scan and whole body MRI supplement
      the imaging depending on tumor type.

PMID- 24903500
TI  - [Biopsy and approach routes for bone tumors. Where and how much is sufficient?].
AB  - Although biopsies are a key step in the diagnosis of bone tumors, they are often
      still referred to as a minor intervention which can be carried out by any surgeon
      as an outpatient procedure or quickly carried out between other more important
      tasks. A biopsy should, however, be regarded as the final part of the diagnostic
      procedure preceded by careful evaluation of the clinical course and analysis of
      the required imaging studies. Although the biopsy procedure seems technically
      simple to perform, an incorrectly performed biopsy can become an obstacle to
      correct tissue analysis (sampling error) and adequate tumor resection and may
      reduce the patient's chances of survival. The principles by which an adequate and
      safe biopsy of bone tumors should be planned and executed are reviewed and the
      surgical approaches to different anatomical locations are presented. 

PMID- 24903501
TI  - [Pathological assessment of bone sarcomas].
AB  - Bone tumors are very rare. Diagnosis and treatment is an interdisciplinary task
      for experienced radiologists, pathologist, and surgeons that is ideally performed
      in specialized centers. For optimal processing of bone specimens, basic
      laboratory equipment and special techniques are required. The cornerstone of the
      histological diagnosis remains H&E staining, supplemented by special stains,
      immunohistochemistry, and molecular techniques. For an appropriate diagnosis,
      data on clinical history, age, location, topography within bone, and imaging are
      required. Major differences between histological and radiological diagnosis have
      to be clarified before starting treatment (e.g., by involving a reference
      registry). 

PMID- 24903502
TI  - [Chemotherapeutic concepts for bone sarcomas].
AB  - BACKGROUND: Osteosarcoma and Ewing sarcoma are the most common chemosensitive
      sarcomas of the bone. AIM: Development in chemotherapeutic concepts as well as
      current and future treatment strategies in osteosarcoma and Ewing sarcoma are
      presented. METHODS: A PubMed search for "Osteosarcoma" and "Ewing sarcoma" was
      performed, and pertinent results were summarized. RESULTS: In both osteosarcoma
      and Ewing sarcoma, outcomes achieved with multimodal treatment concepts combining
      conventional chemotherapy and local treatment have reached a plateau of about 70%
      for 5-year survival rates. DISCUSSION: Improved insights into the molecular
      biology and genetics of the diseases as well as insights into the interactions
      between sarcoma cells and the micro-environment and the immune system are
      necessary to identify novel therapeutic targets in bone sarcomas. Because of the
      rarity of the diseases, multinational cooperation is essential to evaluate novel
      therapies in prospective randomized trials.

PMID- 24903503
TI  - [Surveillance in patients with bone sarcomas. When, how, and for how long?].
AB  - BACKGROUND: The overall survival in patients with typical bone sarcomas such as
      Ewing-sarcoma, osteosarcoma, or chondrosarcoma exceeds 60% in localized disease
      after 5 years. Local or systemic recurrence detected by surveillance may not only
      improve or solve the local problem but also significantly improves the prognosis
      of the patient. Thus, surveillance seems to be justified. OBJECTIVES: As a
      consequence, the questions of how and how long surveillance should be performed
      must be answered. METHODS: A literature review of the last 15 years, discussion
      of review articles, and multidisciplinary expert opinions as published in major
      multinational studies. RESULTS: The decision which surveillance scheme outside of
      clinical studies might be appropriate largely depends on the prognostic benefit
      of early detection of local or systemic recurrence. The detection rate of local
      recurrence by the patient himself is high in extremities. A systematic technical
      examination for the detection of pulmonary metastases is controversial because
      the chance of cure in systemic progression is generally unfavorable. Whether the
      earlier detection of both types of recurrence due to reduced examination
      intervals and/or the use of a CT or MRI is significantly advantageous, remains
      unproven. The duration of surveillance is even less clear. Both local and
      systemic recurrences may be seen more than 10 years after treatment of the
      primary tumor. CONCLUSION: Surveillance makes sense in any case, since the
      detection of a local recurrence is possible already with methods easy to apply.
      Whether and to what extent local imaging is used is left to the individual case.
      Under the current conditions in Germany, local (e.g., MRI) imaging at least every
      6 months during the first 2-3 years, then possibly on an annual basis is
      recommended. There is no evidence-based support for the decision whether and when
      an X-ray of the chest is indicated and whether and when a CT scan should be
      performed. Striking is the lack of prospective studies on surveillance concerning
      both patient- and economically relevant aspects of tumor therapy.

PMID- 24903504
TI  - [Nerve injuries and posttraumatic therapy].
AB  - Peripheral nerve injuries are a common clinical problem and can represent a major
      challenge, especially after trauma. In order to achieve optimal therapy, an early
      and adequate diagnosis with subsequent therapy is critical for functional
      preservation and restoration. Especially after complete severance of a peripheral
      nerve, the surgical techniques for nerve coaptation are an important prerequisite
      for peripheral nerve regeneration. The importance and necessity of adequate nerve
      coaptation and nerve transplantation are presented in detail. In addition, the
      types of primary and secondary nerve reconstruction procedures are described as
      well as the optimal time point of nerve repair. This article provides a
      comprehensive overview of the possibilities for diagnosis and intervention after
      nerve injury, additionally including an algorithm for surgical intervention.
      Furthermore, possible pitfalls and factors for improving the functional outcome
      are presented to optimize results with trauma-related nerve injury. 

PMID- 24903505
TI  - [Funktionsoberarzt. Pseudo-title or meaningful position?].
AB  - The position of the Funktionsoberarzt ("functioning senior physician") is to date
      not specified. Nevertheless, in the majority of hospitals the position exists,
      although the function and responsibilities are not clearly defined. Frequently,
      it is thought that the position represents a consultant who works independently,
      but who is still supported by experienced colleagues to achieve the full
      qualification for a senior physician. In contrast, others indicate that the
      position represents a consultant who works as a senior physician with all
      responsibilities, but without an established post and without the corresponding
      reimbursement. A critical disadvantage of the position is that frequently the
      duties of both a resident and senior physician must be managed. Rotation between
      the two functions results in a higher workload, and the lack of identity and
      acceptance may lead to frustration. Therefore, we feel that the position is only
      meaningful if the Funktionsoberarzt works exclusively as a senior physician who
      is supported for complex surgeries and decisions by more experienced colleagues.
      In addition, the position should only be temporary and the time period for the
      position should be defined in advance. 

PMID- 24903506
TI  - [The position of Funktionsoberarzt at German university clinics].

PMID- 24903507
TI  - [MRI is not suitable for primary screening of wrist injuries and cannot replace
      meticulous examination by a hand surgeon].

PMID- 24903508
TI  - A possible relation between new neuronal recruitment and migratory behavior in
      Acrocephalus warblers.
AB  - Evidence suggests a possible correlation between learning abilities of adults and
      new neuronal recruitment into their brains. The hypothesis is that this brain
      plasticity enables animals to adapt to environmental changes. We examined whether
      there are differences in neuronal recruitment between resident and migrant birds.
      We predicted that migrants, which are more exposed to spatial changes than
      residents, will recruit more new neurons. To test this, we compared neuronal
      recruitment in two closely related bird species - the migrant reed warbler
      (Acrocephalus scirpaceus), and the resident Clamorous warbler (A. Stentoreus) -
      during spring, summer, and autumn. Wild birds were caught, treated with BrdU and
      sacrificed five weeks later. New neurons were recorded in the Hippocampus and
      Nidopallium caudolateral. The results support our hypothesis, as more new neurons
      were found in the migrant species, in both brain regions and all seasons. We
      suggest that this phenomenon enables enhanced navigational abilities, which are
      required for the migratory lifestyle. However, in contrast to our hypothesis, in
      spring we found less new neurons in adults of both species, as compared to other
      seasons. We suggest that in spring, when birds settle in breeding territories,
      they require less spatial skills, and this might enable to reduce the cost of
      neuronal recruitment, as reflected by less new neurons in their brains. We also
      found age differences, with overall higher neuronal recruitment in juveniles.
      Finally, we advocate the importance of studying wild populations, for a better
      understanding of the adaptive significance of neuronal replacement in the
      vertebrate brain.

PMID- 24903509
TI  - Pathogenic role of ganglioside metabolism in neurodegenerative diseases.
AB  - Ganglioside metabolism is altered in several neurodegenerative diseases, and this
      may participate in several events related to the pathogenesis of these diseases.
      Most changes occur in specific areas of the brain and their distinct membrane
      microdomains or lipid rafts. Antiganglioside antibodies may be involved in
      dysfunction of the blood-brain barrier and disease progression in these diseases.
      In lipid rafts, interactions of glycosphingolipids, including ganglioside, with
      proteins may be responsible for the misfolding events that cause the fibril
      and/or aggregate processing of disease-specific proteins, such as alpha
      synuclein, in Parkinson's disease, huntingtin protein in Huntington's disease,
      and copper-zinc superoxide dismutase in amyotrophic lateral sclerosis. Targeting
      ganglioside metabolism may represent an underexploited opportunity to design
      novel therapeutic strategies for neurodegeneration in these diseases.

PMID- 24903510
TI  - An effective approach for coupling direct analysis in real time with atmospheric
      pressure drift tube ion mobility spectrometry.
AB  - Drift tube ion mobility spectrometry (DTIMS) has evolved as a robust analytical
      platform routinely used for screening small molecules across a broad suite of
      chemistries ranging from food and pharmaceuticals to explosives and environmental
      toxins. Most modern atmospheric pressure IM detectors employ corona discharge,
      photoionization, radioactive, or electrospray ion sources for efficient ion
      production. Coupling standalone DTIMS with ambient plasma-based techniques,
      however, has proven to be an exceptional challenge. Device sensitivity with near
      ground ambient plasma sources is hindered by poor ion transmission at the source
      instrument interface, where ion repulsion is caused by the strong electric field
      barrier of the high potential ion mobility spectrometry (IMS) inlet. To overcome
      this shortfall, we introduce a new ion source design incorporating a repeller
      point electrode used to shape the electric field profile and enable ion
      transmission from a direct analysis in real time (DART) plasma ion source.
      Parameter space characterization studies of the DART DTIMS setup were performed
      to ascertain the optimal configuration for the source assembly favoring ion
      transport. Preliminary system capabilities for the direct screening of solid
      pharmaceuticals are briefly demonstrated. 

PMID- 24903511
TI  - Patients with stable coronary artery disease receiving chronic statin treatment
      who are undergoing noncardiac emergency surgery benefit from acute atorvastatin
      reload.
AB  - OBJECTIVE: This study was designed to investigate whether patients with stable
      coronary artery disease (CAD) receiving chronic statin treatment who are
      undergoing noncardiac emergency surgery benefit from acute atorvastatin reload.
      METHODS: A total of 500 patients with stable CAD and regular administration of
      statin before noncardiac emergency surgery were randomized to atorvastatin reload
      (n = 250) or placebo (n = 250). All patients received atorvastatin treatment
      thereafter. The primary end point was a 30-day incidence of major adverse cardiac
      events (MACE). Secondary end points were the incidence of atrial fibrillation
      (AF) during hospitalization and length of hospital stay. RESULTS: The primary end
      point occurred in 2.4% of patients treated with atorvastatin reload and in 8% in
      the placebo arm (p = 0.0088). The incidence of AF during hospitalization was 6.8%
      in patients treated with atorvastatin reload and 17% in the placebo arm (p =
      0.0003). Compared with the placebo arm, the atorvastatin reload arm shortened the
      length of stay (9.8 +/- 3.3 vs. 10.6 +/- 3.5 days, p = 0.009). Multivariable
      analysis suggested that atorvastatin reload conferred a 65% risk reduction of 30
      day MACE (odds ratio 0.35, 95% confidence interval 0.18-0.86; p = 0.005).
      CONCLUSION: The trial suggests that atorvastatin reload may improve the clinical
      outcome of patients with stable CAD receiving chronic statin treatment who are
      undergoing noncardiac emergency surgery.

PMID- 24903514
TI  - Forearm diaphyseal fractures in the adolescent population: treatment and
      management.
AB  - BACKGROUND: Pediatric both-bone diaphyseal forearm fractures are commonly treated
      in a variety of clinical settings. Most often, closed reduction followed by
      immobilization leads to satisfactory results. However, in the adolescent
      population (10-16 years of age), forearm fractures are more challenging due to
      less remodeling potential. The purpose of this review was to provide an overview
      of the anatomy, biomechanics, and treatment options relevant to adolescent
      patients. METHODS: A systematic review of peer-reviewed publications and
      abstracts related to the treatment for pediatric both-bone diaphyseal forearm
      fractures in adolescents was carried out. RESULTS: Forearm fractures in the
      pediatric population are most common following indirect blows to the forearm.
      When treating these fractures using closed reduction, it is important to
      recognize the muscular attachments of the forearm. In roughly 70-90% of cases,
      closed reduction leads to adequate alignment. In all cases, return to function is
      the primary goal; however, exact alignment parameters remain controversial. In
      the adolescent population, surgical treatment has risen substantially in the last
      few decades. Intramedullary nailing and open reduction using plate fixation are
      the two most common operative techniques. Unfortunately, recent results have
      shown that nonunion, malunion, and overall complication rates are higher in older
      pediatric patients. Moreover, no consensus exists regarding one technique over
      another. CONCLUSIONS: Both-bone diaphyseal fractures in the adolescent population
      present unique challenges regarding optimal treatment, especially when
      considering surgical intervention. Further research is necessary to better
      understand indications for specific surgical treatment.

PMID- 24903515
TI  - Automated semantic annotation of rare disease cases: a case study.
AB  - MOTIVATION: As the number of clinical reports in the peer-reviewed medical
      literature keeps growing, there is an increasing need for online search tools to
      find and analyze publications on patients with similar clinical characteristics.
      This problem is especially critical and challenging for rare diseases, where
      publications of large series are scarce. Through an applied example, we
      illustrate how to automatically identify new relevant cases and semantically
      annotate the relevant literature about patient case reports to capture the
      phenotype of a rare disease named cerebrotendinous xanthomatosis. RESULTS: Our
      results confirm that it is possible to automatically identify new relevant case
      reports with a high precision and to annotate them with a satisfactory quality
      (74% F-measure). Automated annotation with an emphasis to entirely describe all
      phenotypic abnormalities found in a disease may facilitate curation efforts by
      supplying phenotype retrieval and assessment of their frequency. Availability and
      Supplementary information: http://www.usc.es/keam/Phenotype Annotation/. Database
      URL: http://www.usc.es/keam/PhenotypeAnnotation/

PMID- 24903516
TI  - Assisted curation of regulatory interactions and growth conditions of OxyR in E.
      coli K-12.
AB  - Given the current explosion of data within original publications generated in the
      field of genomics, a recognized bottleneck is the transfer of such knowledge into
      comprehensive databases. We have for years organized knowledge on transcriptional
      regulation reported in the original literature of Escherichia coli K-12 into
      RegulonDB (http://regulondb.ccg.unam.mx), our database that is currently
      supported by >5000 papers. Here, we report a first step towards the automatic
      biocuration of growth conditions in this corpus. Using the OntoGene text-mining
      system (http://www.ontogene.org), we extracted and manually validated regulatory
      interactions and growth conditions in a new approach based on filters that enable
      the curator to select informative sentences from preprocessed full papers. Based
      on a set of 48 papers dealing with oxidative stress by OxyR, we were able to
      retrieve 100% of the OxyR regulatory interactions present in RegulonDB, including
      the transcription factors and their effect on target genes. Our strategy was
      designed to extract, as we did, their growth conditions. This result provides a
      proof of concept for a more direct and efficient curation process, and enables us
      to define the strategy of the subsequent steps to be implemented for a semi
      automatic curation of original literature dealing with regulation of gene
      expression in bacteria. This project will enhance the efficiency and quality of
      the curation of knowledge present in the literature of gene regulation, and
      contribute to a significant increase in the encoding of the regulatory network of
      E. coli. RegulonDB Database URL: http://regulondb.ccg.unam.mx OntoGene URL:
      http://www.ontogene.org. 

PMID- 24903517
TI  - How do physicians decide to treat: an empirical evaluation of the threshold
      model.
AB  - BACKGROUND: According to the threshold model, when faced with a decision under
      diagnostic uncertainty, physicians should administer treatment if the probability
      of disease is above a specified threshold and withhold treatment otherwise. The
      objectives of the present study are to a) evaluate if physicians act according to
      a threshold model, b) examine which of the existing threshold models [expected
      utility theory model (EUT), regret-based threshold model, or dual-processing
      theory] explains the physicians' decision-making best. METHODS: A survey
      employing realistic clinical treatment vignettes for patients with pulmonary
      embolism and acute myeloid leukemia was administered to forty-one practicing
      physicians across different medical specialties. Participants were randomly
      assigned to the order of presentation of the case vignettes and re-randomized to
      the order of "high" versus "low" threshold case. The main outcome measure was the
      proportion of physicians who would or would not prescribe treatment in relation
      to perceived changes in threshold probability. RESULTS: Fewer physicians choose
      to treat as the benefit/harms ratio decreased (i.e. the threshold increased) and
      more physicians administered treatment as the benefit/harms ratio increased (and
      the threshold decreased). When compared to the actual treatment recommendations,
      we found that the regret model was marginally superior to the EUT model [Odds
      ratio (OR) = 1.49; 95% confidence interval (CI) 1.00 to 2.23; p = 0.056]. The
      dual-processing model was statistically significantly superior to both EUT model
      [OR = 1.75, 95% CI 1.67 to 4.08; p < 0.001] and regret model [OR = 2.61, 95% CI
      1.11 to 2.77; p = 0.018]. CONCLUSIONS: We provide the first empirical evidence
      that physicians' decision-making can be explained by the threshold model. Of the
      threshold models tested, the dual-processing theory of decision-making provides
      the best explanation for the observed empirical results.

PMID- 24903518
TI  - Mechanisms underlying the effect of acupuncture on cognitive improvement: a
      systematic review of animal studies.
AB  - Acupuncture has been reported to be beneficial in treating cognitive impairment
      in various pathological conditions. This review describes the effort to
      understand the signaling pathways that underlie the acupunctural therapeutic
      effect on cognitive function. We searched the literature in 12 electronic
      databases from their inception to November 2013, with full text available and
      language limited to English. Twenty-three studies were identified under the
      selection criteria. All recruited animal studies demonstrate a significant
      positive effect of acupuncture on cognitive impairment. Findings suggest
      acupuncture may improve cognitive function through modulation of signaling
      pathways involved in neuronal survival and function, specifically, through
      promoting cholinergic neural transmission, facilitating dopaminergic synaptic
      transmission, enhancing neurotrophin signaling, suppressing oxidative stress,
      attenuating apoptosis, regulating glycometabolic enzymes and reducing microglial
      activation. However, the quality of reviewed studies has room for improvement.
      Further high-quality animal studies with randomization, blinding and estimation
      of sample size are needed to strengthen the recognition of group differences. 

PMID- 24903522
TI  - Intubation conditions in young infants after propofol and remifentanil induction
      with and without low-dose rocuronium.
AB  - BACKGROUND: Bolus injections of intravenous propofol and remifentanil can be used
      in the tracheal intubation of infants and children, but relatively large doses
      are needed. We hypothesised that addition of a small bolus of rocuronium would
      ensure good intubation conditions when modest propofol and remifentanil doses
      were used. METHODS: Seventy infants between 3 weeks and 4 months of age were
      randomised to receive either placebo or rocuronium. Anaesthesia was induced with
      IV propofol, 3 (3-5) mg/kg [median (range)]. Rocuronium (0.2 mg/kg) or placebo
      was then injected, followed 15 s later by 2 MUg/kg remifentanil. One anaesthetist
      attempted tracheal intubation 1 min after the rocuronium/placebo injection and
      used the 'Copenhagen scoring system' to assess intubation conditions. The
      neuromuscular effect of 0.2 mg/kg rocuronium was recorded in another eight,
      already intubated, infants using thumb accelerometry during train-of-four
      stimulation of the ulnar nerve. RESULTS: Intubation conditions were classified as
      'poor' in 14 of 34 (41%) patients given placebo and in 10 of 36 (28%) patients
      given rocuronium (P = 0.32). There were four failed first attempts at intubation
      in the placebo group and none in the rocuronium group (P = 0.051). Maximum
      neuromuscular depression occurred 4 (3-8) after injection of 0.2 mg/kg
      rocuronium. CONCLUSIONS: Intubation conditions were poor in almost one third of
      the patients receiving propofol-remifentanil. Adding a low-dose rocuronium did
      not significantly improve intubation conditions.

PMID- 24903523
TI  - Novel isopolyoxotungstate [H2W11O38]8- based metal organic framework: as Lewis
      acid catalyst for cyanosilylation of aromatic aldehydes.
AB  - A novel polyoxometalate-based metal organic framework (POMOF) constructed from
      isolated isopolyoxotungstate [H2W11O38](8-) cluster,
      {[Cu2(bpy)(H2O)5.5]2[H2W11O38].3H2O.0.5CH3CN} (1, where bpy = 4,4'-bpydine), has
      been synthesized under solvothermal conditions and charaterized by elemental
      analysis, infrared spectroscopy, and single-crystal X-ray diffraction. In 1,
      {W11} clusters are alternately linked by two [Cu(2)(H2O)1.5(Ot)3(N)](2+) cations
      in an unexpected end-to-end fashion leading to a one-dimensional (1D) chain.
      Adjacent 1D chains are linked through Cu(1)-bpy-Cu(2) in an opposite direction to
      form a two-dimensional (2D) wavelike sheet along the ab plane. These 2D sheets
      are further stacked in a parallel fashion giving rise to the 1D channels with
      copper(II) cations aligned in the channels. The resulting POMOF acted as a Lewis
      acid catalyst through a heterogeneous manner to prompt cyanosilylation with
      excellent efficiency. 

PMID- 24903519
TI  - Conservation of streptococcal CRISPRs on human skin and saliva.
AB  - BACKGROUND: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)
      are utilized by bacteria to resist encounters with their viruses. Human body
      surfaces have numerous bacteria that harbor CRISPRs, and their content can
      provide clues as to the types and features of viruses they may have encountered.
      RESULTS: We investigated the conservation of CRISPR content from streptococci on
      skin and saliva of human subjects over 8-weeks to determine whether similarities
      existed in the CRISPR spacer profiles and whether CRISPR spacers were a stable
      component of each biogeographic site. Most of the CRISPR sequences identified
      were unique, but a small proportion of spacers from the skin and saliva of each
      subject matched spacers derived from previously sequenced loci of S. thermophilus
      and other streptococci. There were significant proportions of CRISPR spacers
      conserved over the entire 8-week study period for all subjects, and salivary
      CRISPR spacers sampled in the mornings showed significantly higher levels of
      conservation than any other time of day. We also found substantial similarities
      in the spacer repertoires of the skin and saliva of each subject. Many skin
      derived spacers matched salivary viruses, supporting that bacteria of the skin
      may encounter viruses with similar sequences to those found in the mouth. Despite
      the similarities between skin and salivary spacer repertoires, the variation
      present was distinct based on each subject and body site. CONCLUSIONS: The
      conservation of CRISPR spacers in the saliva and the skin of human subjects over
      the time period studied suggests a relative conservation of the bacteria
      harboring them.

PMID- 24903525
TI  - Programmes to support international medical graduate doctors.

PMID- 24903524
TI  - Improved small molecule drug release from in situ forming poly(lactic-co-glycolic
      acid) scaffolds incorporating poly(beta-amino ester) and hydroxyapatite
      microparticles.
AB  - In situ forming implants are an attractive choice for controlled drug release
      into a fixed location. Currently, rapidly solidifying solvent exchange systems
      suffer from a high initial burst, and sustained release behavior is tied to
      polymer precipitation and degradation rate. The present studies investigated
      addition of hydroxyapatite (HA) and drug-loaded poly(beta-amino ester) (PBAE)
      microparticles to in situ forming poly(lactic-co-glycolic acid) (PLGA)-based
      systems to prolong release and reduce burst. PBAEs were synthesized, imbibed with
      simvastatin (osteogenic) or clodronate (anti-resorptive), and then ground into
      microparticles. Microparticles were mixed with or without HA into a PLGA
      solution, and the mixture was injected into buffer, leading to precipitation and
      creating solid scaffolds with embedded HA and PBAE microparticles. Simvastatin
      release was prolonged through 30 days, and burst release was reduced from 81 to
      39% when loaded into PBAE microparticles. Clodronate burst was reduced from 49 to
      32% after addition of HA filler, but release kinetics were unaffected after
      loading into PBAE microparticles. Scaffold dry mass remained unchanged through
      day 15, with a pronounced increase in degradation rate after day 30, while wet
      scaffolds experienced a mass increase through day 25 due to swelling. Porosity
      and pore size changed throughout degradation, likely due to a combination of
      swelling and degradation. The system offers improved release kinetics, multiple
      release profiles, and rapid solidification compared to traditional in situ
      forming implants. 

PMID- 24903526
TI  - Effects of a diabetes prevention programme on weight-specific quality of life in
      Latino youth.
AB  - OBJECTIVE: To examine the effects of a diabetes prevention programme on weight
      specific Quality of Life (QOL) in obese Latino youth. METHODS: Fifteen obese
      Latino adolescents (body mass index % = 96.4 +/- 1.2; age = 15.0 +/- 1.0)
      completed a 12-week culturally grounded, community-based intervention designed to
      improve physical and psychosocial health. Weight-specific QOL was assessed by the
      Youth Quality of Life-Weight module and compared with age, sex and ethnicity
      matched lean youth. RESULTS: At baseline, intervention youth exhibited
      significantly lower weight-specific QOL compared with lean youth (70.8 +/- 5.4
      vs. 91.2 +/- 2.2, P = 0.002). However, following the intervention, total weight
      specific QOL increased by 21.8% among obese youth (70.8 +/- 5.4 to 86.2 +/- 4.3,
      P < 0.001) and was no longer different from lean controls. Significant increases
      in weight-specific QOL were noted across all subdomains including self (45.7%),
      social (11.9%) and environmental (36.2%) despite the fact that weight did not
      change (90.6 +/- 6.8 to 89.9 +/- 7.2, P = 0.44). The improvements in QOL were
      maintained for up to 12 months after the intervention. CONCLUSION: Weight
      specific QOL among obese Latino youth can be improved through lifestyle
      interventions to a level similar to lean peers. Further, weight loss may not be
      necessary to observe improvements in QOL.

PMID- 24903528
TI  - Bilateral reperfusion injury after carotid endarterectomy with contralateral
      carotid occlusion.
AB  - Cerebral hyperperfusion syndrome represents a clinical spectrum characterized by
      severe unilateral headache, acute changes in mental status, vomiting, seizures,
      focal neurologic deficits, and, in its most severe form, intracranial hemorrhage.
      With the exception of one early case report, reperfusion injury to the brain
      following carotid endarterectomy has been reported only ipsilateral to the side
      of surgery. We report the unique case of a patient with symptomatic severe right
      internal carotid artery stenosis and contralateral carotid occlusion who
      underwent carotid endarterectomy complicated by cerebral hyperperfusion syndrome
      and associated bilateral intracranial hemorrhage. 

PMID- 24903527
TI  - Molecular determinants for the high constitutive activity of the human histamine
      H4 receptor: functional studies on orthologues and mutants.
AB  - BACKGROUND AND PURPOSE: Some histamine H4 receptor ligands act as inverse
      agonists at the human H4 receptor (hH4 R), a receptor with exceptionally high
      constitutive activity, but as neutral antagonists or partial agonists at the
      constitutively inactive mouse H4 receptor (mH4 R) and rat H4 receptor (rH4 R). To
      study molecular determinants of constitutive activity, H4 receptor reciprocal
      mutants were constructed: single mutants: hH4 R-F169V, mH4 R-V171F, hH4 R-S179A,
      hH4 R-S179M; double mutants: hH4 R-F169V+S179A, hH4 R-F169V+S179M and mH4 R
      V171F+M181S. EXPERIMENTAL APPROACH: Site-directed mutagenesis with pVL1392
      plasmids containing hH4 or mH4 receptors were performed. Wild-type or mutant
      receptors were co-expressed with Galphai2 and Gbeta1 gamma2 in Sf9 cells.
      Membranes were studied in saturation and competition binding assays ([(3) H]
      histamine), and in functional [(35) S]-GTPgammaS assays with inverse, partial and
      full agonists of the hH4 receptor. KEY RESULTS: Constitutive activity decreased
      from the hH4 receptor via the hH4 R-F169V mutant to the hH4 R-F169V+S179A and hH4
      R-F169V+S179M double mutants. F169 alone or in concert with S179 plays a major
      role in stabilizing a ligand-free active state of the hH4 receptor. Partial
      inverse hH4 receptor agonists like JNJ7777120 behaved as neutral antagonists or
      partial agonists at species orthologues with lower or no constitutive activity.
      Some partial and full hH4 receptor agonists showed decreased maximal effects and
      potencies at hH4 R-F169V and double mutants. However, the mutation of S179 in the
      hH4 receptor to M as in mH4 receptor or A as in rH4 receptor did not
      significantly reduce constitutive activity. CONCLUSIONS AND IMPLICATIONS: F169
      and S179 are key amino acids for the high constitutive activity of hH4 receptors
      and may also be of relevance for other constitutively active GPCRs. LINKED
      ARTICLES: This article is part of a themed issue on Histamine Pharmacology Update
      published in volume 170 issue 1. To view the other articles in this issue visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.2013.170.issue-1/issuetoc.

PMID- 24903529
TI  - Late onset venous thoracic outlet syndrome following clavicle non-union fracture:
      A case report.
AB  - A 59-year-old woman was admitted three times over a six-month period with
      recurrent upper extremity deep venous thrombosis (UEDVT). It was determined that
      this patient was suffering from an unusual presentation of Paget-Schroetter
      syndrome secondary to a 20-year-old non-union of a midshaft clavicle fracture.
      Following thrombolysis the patient underwent resection and plate fixation of the
      clavicle fracture non-union. Despite the anatomic proximity of the subclavian
      vessels to the clavicle, vascular complications from fracture are rare. Treatment
      of midshaft clavicle fractures is often non-operative. Non-union rates are
      generally less than 10%, and easily treated secondarily without complication.
      Clavicular pseudo-arthroses from trauma have been implicated in the development
      of the thoracic outlet syndromes, however, onset 20 years after fracture has
      never before been reported.

PMID- 24903530
TI  - A rare cause of massive haematuria: Internal iliac artery-ureteric fistula.
AB  - Ureteric fistula into the arterial tree is a well-recognised, but uncommon
      condition. The involvement of internal iliac artery is rare. We present a rare
      case of fistulous communication and subsequent infection of an internal iliac
      artery aneurysm and ureter secondary to insertion of ureteric stent following
      endovascular exclusion of the aneurysm and its management. Nephrostogram
      identified the fistula not seen on computerised tomography. This case highlights
      the awareness of such pathology allowing for prompt recognition of the condition
      and importance of appropriate imaging.

PMID- 24903533
TI  - Design, synthesis and evaluation of rhodanine derivatives as aldose reductase
      inhibitors.
AB  - Aldose reductase (ALR) enzyme plays a significant role in conversion of excess
      amount of glucose into sorbitol in diabetic condition, inhibitors of which
      decrease the secondary complication of diabetes mellitus. To understand the
      structural interaction of inhibitors with ALR enzyme and develop more effective
      ALR inhibitors, a series of substituted 5-phenylbenzoate containing N-substituted
      rhodanine derivatives were synthesized and evaluated for their in vitro ALR
      inhibitory activity. Docking studies of these compounds were carried out, which
      revealed that the 5-phenylbenzoate moiety deeply influenced the key pi-pi
      stacking while 4-oxo-2-thioxothiazolidines contributed in hydrogen bond
      interactions. The phenyl ring of benzylidene system occupied in specific pocket
      constituted from Phe115, Phe122, Leu300 and Cys303 while the rhodanine ring forms
      a tight net of hydrogen bond with Val47 at anionic binding site of the enzyme.
      The structural insights obtained from the docking study gave better understanding
      of rhodanine and macromolecular interaction and will help us in further designing
      and improving of ALR inhibitory activity of rhodanine analogs. 

PMID- 24903532
TI  - Feasibility of multianimal hyperpolarized (13) C MRS.
AB  - PURPOSE: There is great potential for real-time investigation of metabolism with
      MRS and hyperpolarized (HP) (13) C agents. Unfortunately, HP technology has high
      associated costs and efficiency limitations that may constrain in vivo studies
      involving many animals. To improve the throughput of preclinical investigations,
      we evaluate the feasibility of performing HP MRS on multiple animals
      simultaneously. METHODS: Simulations helped assess the viability of a dual-coil
      strategy for spatially localized multivolume MRS. A dual-mouse system was
      assembled and characterized with bench- and scanner-based experiments. Enzyme
      phantoms mixed with HP [1-(13) C] pyruvate emulated real-time metabolism and
      offered a controlled mechanism for evaluating system performance. Finally, a
      normal mouse and a mouse bearing a subcutaneous xenograft of colon cancer were
      simultaneously scanned in vivo using an agent containing HP [1-(13) C] pyruvate.
      RESULTS: Geometric separation/rotation, active decoupling, and use of low input
      impedance preamplifiers permitted an encode-by-channel approach for spatially
      localized MRS. A precalibrated shim allowed straightforward metabolite
      differentiation in enzyme phantom and in vivo experiments at 7 Tesla, with
      performance similar to conventional acquisitions. CONCLUSION: The initial
      feasibility of multi-animal HP (13) C MRS was established. Throughput scales with
      the number of simultaneously scanned animals, demonstrating the potential for
      significant improvements in study efficiency.

PMID- 24903534
TI  - Biodeterioration of epoxy resin: a microbial survey through culture-independent
      and culture-dependent approaches.
AB  - During the 20th century, synthetic polymers were greatly used in the field of
      art. In particular, the epoxy resins were used for both conservation and for
      creating sculptures. The biodeterioration of these polymers has not been
      adequately studied. The aim of this investigation was to examine the microflora
      responsible for the deterioration of an epoxy statue exposed to outdoor
      conditions. Fungal and bacterial microflora were isolated from the art object,
      clustered by fluorescence-ITS (internal transcribed spacer), identified by ITS
      and 16S rRNA sequencing and tested for their lipolytic abilities by three agar
      assays. Different algal, bacterial, cyanobacterial and fungal clone libraries
      were constructed. The surrounding airborne microflora was analyzed using culture
      dependent and culture-independent approaches. The results indicated the presence,
      on the statue surface, of an interesting and differentiate microbial community
      composed of rock-inhabiting members, algal photobionts (Trebouxia spp.,
      Chloroidium ellipsoideum and Chlorella angustoellipsoidea), Cyanobacteria
      (Leptolyngbya sp., Phormidium sp., Cylindrospermum stagnale, Hassallia byssoidea
      and Geitlerinema sp.), black yeasts related to the species Friedmanniomyces
      endolithicus, Pseudotaeniolina globosa, Phaeococcomyces catenatus and
      Catenulostroma germanicum and several plant-associated fungi. This investigation
      provides new information on the potential microfloral inhabitants of epoxy resin
      discovering a new ecological niche, occupied mainly by several members of rock
      colonizing microbial species. 

PMID- 24903535
TI  - A repeated cross-sectional study of socio-economic inequities in dietary sodium
      consumption among Canadian adults: implications for national sodium reduction
      strategies.
AB  - INTRODUCTION: In many countries including Canada, excess consumption of dietary
      sodium is common, and this has adverse implications for population health. Socio
      economic inequities in sodium consumption seem likely, but research is limited.
      Knowledge of socio-economic inequities in sodium consumption is important for
      informing population-level sodium reduction strategies, to ensure that they are
      both impactful and equitable. METHODS: We examined the association between socio
      economic indicators (income and education) and sodium, using two outcome
      variables: 1) sodium consumption in mg/day, and 2) reported use of table salt, in
      two national surveys: the 1970/72 Nutrition Canada Survey and the 2004 Canadian
      Community Health Survey, Cycle 2.2. This permitted us to explore whether there
      were any changes in socio-economic patterning in dietary sodium during a time
      period characterized by modest, information-based national sodium reduction
      efforts, as well as to provide baseline information against which to examine the
      impact (equitable or not) of future sodium reduction strategies in Canada.
      RESULTS: There was no evidence of a socio-economic inequity in sodium consumption
      (mg/day) in 2004. In fact findings pointed to a positive association in women,
      whereby women of higher education consumed more sodium than women of lower
      education in 2004. For men, income was positively associated with reported use of
      table salt in 1970/72, but negatively associated in 2004. CONCLUSIONS: An
      emerging inequity in reported use of table salt among men could reflect the
      modest, information-based sodium reduction efforts that were implemented during
      the time frame considered. However, for sodium consumption in mg/day, we found no
      evidence of a contemporary inequity, and in fact observed the opposite effect
      among women. Our findings could reflect data limitations, or they could signal
      that sodium differs from some other nutrients in terms of its socio-economic
      patterning, perhaps reflecting very high prevalence of excess consumption. It is
      possible that socio-economic inequities in sodium consumption will emerge as
      excess consumption declines, consistent with fundamental cause theory. It is
      important that national sodium reduction strategies are both impactful and
      equitable.

PMID- 24903537
TI  - Relationship between self-reported sleep quality and metabolic syndrome in
      general population.
AB  - BACKGROUND: To examine an association between self-reported sleep quality
      determined by Pittsburgh sleep quality index (PSQI) and metabolic syndrome.
      METHODS: This study was designed as cross-sectional study. Participants were 1481
      adults aged 20 years and above from general population (549 males and 932
      females). We assessed the global sleep quality by PSQI. PSQI consists of 7
      elements, i.e. subjective sleep quality, sleep latency (prolonged sleep onset
      time), sleep duration, habitual sleep efficiency (proportion of hours slept to
      hours spent in bed), sleep disturbance (interruption of sleep), use of sleep
      medication and daytime dysfunction (trouble staying awake while engaging in
      social activity). Any participants with score of 6 or more are diagnosed to have
      sleep disorder. We also assessed the above 7 elements, which consisted of a four
      grade system (i.e. 0, 1, 2, 3). Metabolic syndrome consisted of abdominal
      obesity, hypertension, impaired glucose tolerance and dyslipidemia. Diagnosis of
      metabolic syndrome was done when the participants have abdominal obesity and meet
      two or more other components. All analyses were adjusted by age, drinking habit,
      smoking habit, working hours, exercise habit and depression. RESULTS: Fifty-two
      male participants (9.5%) and 133 female (14.3%) scored 6 or more points in global
      PSQI score. The global PSQI score, sleep latency score and sleep disturbance
      score of participants with metabolic syndrome were higher level than those
      without the condition (p < 0.001, p = 0.009, p = 0.025 for male and p < 0.001, p
      < 0.001, p = 0.002 for females, respectively). The odds ratio of metabolic
      syndrome among participants with PSQI score of 6 or more points were 2.37 (95%
      confidence interval: 1.23-4.58) for males and 2.71 (1.45-5.07) for females in
      contrast to those with 5 or less points. The odds ratio of metabolic syndrome
      with sleep latency score of 2 was 2.65 (1.14-6.15) for male and 3.82 (1.81-8.09)
      for females in contrast with those of 0. The odds ratio of metabolic syndrome
      with sleep disturbance score of 1 was 1.76 (1.09-2.86) for males and 2.43 (1.26
      4.69) for females in contrast with those of 0. CONCLUSIONS: Global PSQI score and
      its components (especially, sleep latency and sleep disturbance) were associated
      with metabolic syndrome.

PMID- 24903536
TI  - Prenatal nicotine exposure selectively affects nicotinic receptor expression in
      primary and associative visual cortices of the fetal baboon.
AB  - Exposure to nicotine during pregnancy via maternal cigarette smoking is
      associated with visual deficits in children. This is possibly due to the
      activation of nicotinic acetylcholine receptors (nAChRs) in the occipital cortex,
      which are important in the development of visual mapping. Using a baboon model,
      we explored the effects of prenatal nicotine on parameters in the primary and
      associated visual cortices. Pregnant baboons were infused with nicotine (0.5
      mg/h, intravenous) or saline from 86 days gestation. At 161 days gestation, fetal
      brains were collected (n = 5 per group) and the occipital lobe assessed for
      nAChRs and markers of the serotonergic and catecholaminergic systems using tissue
      autoradiography and/or high-performance liquid chromatography. Neuronal nAChRs
      and serotonergic markers were expressed in a region- and subunit-dependent
      manner. Prenatal nicotine exposure was associated with increased binding for (3)
      H-epibatidine sensitive nAChRs in the primary visual cortex [Brodmann areas (BA)
      17] and BA 18, but not BA 19, of the associative visual cortex (P < 0.05).
      Markers of the serotonergic or catecholaminergic systems were not significantly
      altered. Thus, prenatal nicotine exposure is associated with alterations in the
      cholinergic system in the occipital lobe, which may aid in the explanation of the
      appearance of visual deficits in children from mothers who smoke during
      pregnancy. 

PMID- 24903538
TI  - A review of the evidence for dietary interventions in preventing or slowing the
      progression of age-related macular degeneration.
AB  - PURPOSE: To summarise the results of recent Cochrane systematic reviews that have
      investigated whether nutritional supplements prevent or slow the progression of
      age-related macular degeneration (AMD). RECENT FINDINGS: There is no good
      evidence from randomised controlled trials that the general population should be
      taking antioxidant vitamin supplements to reduce their risk of developing AMD
      later on in life. By contrast, there is moderate quality evidence that people
      with AMD may experience a delay in progression by taking specific antioxidant
      vitamin and mineral supplements. This finding is drawn from one large randomised
      controlled trial conducted in the USA in a relatively well-nourished population.
      Although observational studies have shown that the consumption of dietary omega 3
      long chain polyunsaturated fatty acids may reduce the risk of progression to
      advanced AMD, two recently published randomised controlled trials failed to show
      any benefit of omega 3 supplements on AMD progression. SUMMARY: There is no high
      quality experimental evidence that nutritional supplementation is beneficial for
      the primary prevention of AMD. However, people with AMD may benefit from
      supplementation with antioxidant vitamins. There is currently no evidence to
      support increasing levels of omega 3 long chain polyunsaturated fatty acids in
      the diet for the explicit purpose of preventing or slowing the progression of
      AMD.

PMID- 24903539
TI  - Death-defining immune responses after apoptosis.
AB  - Apoptosis is a programmed form of cell death whereby characteristic internal
      cellular dismantling is accompanied by the preservation of plasma membrane
      integrity. Maintaining this order during apoptosis prevents the release of
      cellular contents and ensures a noninflammatory death. Here, we consider examples
      of apoptosis in different contexts and discuss how the same form of cell death
      could have different immunological consequences. Multiple parameters such as cell
      death as a result of microbial infection, the nature of the inflammatory
      microenvironment, the type of responding phagocytic cells and the genetic
      background of the host organism all differentially influence the immunological
      consequences of apoptosis. 

PMID- 24903540
TI  - Severity of arterial and chronic thromboembolic pulmonary hypertension is
      associated with impairment of heart rate turbulence.
AB  - BACKGROUND: Heart rate turbulence (HRT) impairment is a validated and an
      independent indicator of cardiovascular death. There are limited data on HRT in
      pulmonary hypertension (PH), so we assessed potential HRT alterations in PH,
      especially in relation to its severity. METHODS: Thirty-three out of 41 patients
      were enrolled in the study aged 49.7 +/- 15.9 years (22 with arterial, 11 with
      chronic thromboembolic PH). Routine evaluations, right heart catheterization, and
      24-hour Holter monitoring with heart rate variability and HRT assessment were
      performed. RESULTS: HRT was significantly impaired in PH patients, as compared to
      25 healthy controls: mean turbulence onset (TO) was -0.27% versus -2.60% (P <
      0.0001), and median turbulence slope (TS) was 3.13 versus 13.5 msRR (P < 0.0001).
      Abnormal HRT (TO >= 0.0% and/or TS <= 2.5 ms/RR) was found in 63.3% of PH
      patients. Patients with PH and abnormal HRT presented more compromised
      functional, biochemical, and hemodynamic status than PH patients with normal TO
      and TS values. Multivariate stepwise regression analysis showed that TO value was
      related to oxygen desaturation <90% in 6-minute walking test (6-MWT; OR 0.41, P <
      0.001) and was related to N-Terminal pro-B type Natriuretic Peptide concentration
      (OR 0.40, P < 0.001); TS was related to 6-MWT distance (OR 0.53, P < 0.0001).
      CONCLUSIONS: Patients with arterial or chronic thromboembolic PH are
      characterized by significant impairment of HRT which is related to the disease
      severity. We hypothesize that patients with abnormal HRT could be considered as
      subjects with an increased risk of cardiovascular death, however, it needs
      further investigation.

PMID- 24903541
TI  - Somatic mosaicism for the p.His1047Arg mutation in PIK3CA in a girl with
      mesenteric lipomatosis.
AB  - We describe a patient who presented with a localized growth of mature fat tissue,
      which was surgically removed. MRI imaging identified diffuse increase in visceral
      adipose tissue. Targeted deep sequencing of the resected tissue uncovered a
      p.H1047R variant in PIK3CA, which was absent in blood. This report expands the
      phenotypic spectrum of mosaic PIK3CA mutations.

PMID- 24903542
TI  - Caesarean delivery is associated with childhood general obesity but not abdominal
      obesity in Iranian elementary school children.
AB  - AIM: This study examined the association between Caesarean delivery and general
      and abdominal obesity among children. METHODS: In a cross-sectional study, 635
      children aged from 6 to 12 years of age (476 girls and 159 boys) were randomly
      selected from Isfahan elementary schools. Weight, height and waist circumference
      were measured. General obesity and abdominal obesity were defined based on World
      Health Organization growth charts and Iranian national cut-off points,
      respectively. Parents were asked about delivery type and other factors
      potentially related to childhood obesity using a self-administered questionnaire.
      The association between delivery type and obesity was examined using univariate
      and multivariate logistic regression models. RESULTS: The overall prevalence of
      general and central obesity was 17.6% and 17.1%, respectively, and Caesarean
      delivery was significantly associated with general obesity after controlling for
      potential confounders (OR: 2.46; 95% CI: 1.30-4.63, p = 0.005). We observed a
      significant association between Caesarean delivery and abdominal obesity in crude
      analyses (OR: 1.66; 1.02-2.69, p = 0.04), but this disappeared after adjusting
      for covariates (OR: 1.96; 0.82-4.69, p = 0.13). CONCLUSION: Our results suggest
      that Caesarean delivery is adversely associated with general childhood obesity,
      but not abdominal obesity. This provides support for recommending vaginal births,
      unless contraindicated. Further research in large populations is required to
      confirm these findings.

PMID- 24903543
TI  - Should renal function become an important factor in cognitive impairment and
      cognitive decline?

PMID- 24903544
TI  - Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas
      -a randomized clinical trial.
AB  - BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal
      cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours.
      Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate
      (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate efficacy and
      safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high
      risk nBCC. METHODS: Patients with histologically verified facial nBCC (n = 32)
      defined as high-risk tumours were included; diameter > 15 mm, tumours located in
      high-risk zones, or on severely sun-damaged skin. Tumours were debulked and
      patients randomized to either AFXL-PDT (n = 16) or PDT (n = 16). Fractional CO2
      laser treatment was applied at 5% density and 1000 MUm (80 mJ) ablation depth.
      MAL was applied under occlusion for 3 h and illuminated with a 633-nm light
      emitting diode source, 37 J cm(-2) . Clinical assessments were performed at 3, 6,
      9 and 12 months and biopsies were taken at 12 months. RESULTS: Clinical cure
      rates at 3 months were 100% (16 of 16 AFXL-PDT) and 88% (14 of 16 PDT, P =
      0.484). Recurrences tended to occur later and in lower numbers after AFXL-PDT at
      6, 9 and 12 months (6%, 19%, 19%) than PDT (25%, 38%, 44%) (P = 0.114). Histology
      at 12 months documented equal tumour clearance after AFXL-PDT (63%, 10 of 16) and
      PDT (56%, 9 of 16). Cosmetic outcomes were highly satisfactory after both
      treatments (P > 0.090). CONCLUSIONS: Long-term efficacy was similar after PDT and
      AFXL-PDT with a trend for a favourable short-term cure rate after AFXL-PDT. AFXL
      PDT needs further refinement for nBCC and at present is not recommended over PDT.

PMID- 24903545
TI  - Butyricimonas faecihominis sp. nov. and Butyricimonas paravirosa sp. nov.,
      isolated from human faeces, and emended description of the genus Butyricimonas.
AB  - Two bacterial strains, designated 180-3(T) and 214-4(T), isolated from human
      faeces were characterized by using a polyphasic taxonomic approach that included
      analysis of their phenotypic and biochemical features, cellular fatty acid
      profiles, menaquinone profiles and phylogenetic positions based on 16S rRNA gene
      sequence analysis. 16S rRNA gene sequence analysis showed that these strains
      represented members of the genus Butyricimonas. These strains shared 97.9 % 16S
      rRNA gene sequence similarity with each other and were related to Butyricimonas
      virosa JCM 15149(T) (97 % sequence similarity) and Butyricimonas synergistica JCM
      15148(T) (94-95 %). Although strain 180-3(T) was related to (but distinct from)
      B. virosa JCM 15149(T) and B. synergistica JCM 15148(T), with hsp60 gene sequence
      similarities of 89.4 and 84.6 %, respectively, strain 214-4(T) exhibited high
      hsp60 gene sequence similarity (100 %) with B. virosa JCM 15149(T) and was
      different from B. synergistica JCM 15148(T) (83.5 %). DNA-DNA hybridization
      experiments demonstrated a genomic distinction of strains 180-3(T) and 214-4(T)
      from B. virosa JCM 15149(T) and B. synergistica JCM 15148(T). The strains were
      obligately anaerobic, non-pigmented, non-spore-forming, non-motile, Gram-stain
      negative rods. Growth of the strains was inhibited on medium containing 20 %
      bile. The two strains produced butyric and isobutyric acids as the end products
      from glucose, as has been observed in the other two species of the genus
      Butyricimonas. The major cellular fatty acid of strains 180-3(T) and 214-4(T) was
      iso-C15 : 0. The major menaquinone of the isolates was MK-10 (>50 %). Strains 180
      3(T) and 214-4(T) have DNA G+C contents of 45 mol%. On the basis of these data,
      strains 180-3(T) and 214-4(T) represent two novel species of the genus
      Butyricimonas, for which the names Butyricimonas faecihominis sp. nov. and
      Butyricimonas paravirosa sp. nov., respectively, are proposed. The type strains
      of B. faecihominis and B. paravirosa are 180-3(T) ( = JCM 18676(T) = CCUG
      65562(T)) and 214-4(T) ( = JCM 18677(T) = CCUG 65563(T)), respectively. 

PMID- 24903546
TI  - Wireless accelerometry is feasible in acute monitoring of upper limb motor
      recovery after ischemic stroke.
AB  - BACKGROUND: Clinical deterioration in the acute stage of ischemic stroke
      powerfully predicts outcome and may serve as a marker for urgent intervention.
      However, accurate monitoring of acute stroke patients is hampered by the lack of
      validated continuous monitoring devices. We sought to assess the use of wireless
      accelerometry in this setting, hypothesizing that stroke patients would have a
      greater difference in movement between upper limbs than controls and that the
      magnitude of correlation between upper limb movements would be negatively
      associated with the National Institutes of Health Stroke Scale (NIHSS) score.
      METHODS: In this pilot study, 20 patients with acute ischemic stroke and
      unilateral upper limb weakness and 10 controls were recruited from a
      comprehensive stroke centre. All subjects were fitted with two 3-axis
      accelerometers and underwent 24 h of continuous accelerometry recording of upper
      limb movements and repeat NIHSS assessments. The intra-class correlation
      coefficient (ICC), assessing the similarity (or otherwise) of spontaneous
      movements in each arm was calculated. The association between NIHSS (total and
      motor subset scores) and the magnitude of ICC was estimated by Spearman's rank
      correlation, receiver-operating characteristic curve analysis was performed and
      the optimal diagnostic threshold value of ICC was calculated. RESULTS: The
      magnitude of the ICC was significantly associated with the baseline NIHSS score
      (p = 0.02) and non-significantly associated with the baseline NIHSS motor score
      (p = 0.08). At the optimal diagnostic threshold of ICC magnitude = 0.7, wireless
      accelerometry distinguished patients from controls with a sensitivity of 0.95, a
      specificity of 0.6 and a diagnostic odds ratio of 28.5. CONCLUSIONS: The wireless
      accelerometry system successfully detects a motor deficit in the setting of acute
      ischemic stroke, accurately differentiating patients from controls, and
      correlates well with the baseline NIHSS score. Its use is feasible in the acute
      stroke setting. Overall, it shows promise as a diagnostic tool to continuously
      monitor acute stroke patients but requires validation in a larger trial.

PMID- 24903550
TI  - Long-term follow-up of thalamic deep brain stimulation for essential tremor -
      patient satisfaction and mortality.
AB  - BACKGROUND: Ventral intermediate thalamic nucleus (VIM) deep brain stimulation
      (DBS) is an effective treatment for tremor, but there is limited data on long
      term efficacy and mortality after VIM-DBS. Here we report the analysis of patient
      satisfaction and mortality in all patients treated in our center 1996-2010 with
      VIM-DBS for essential tremor (ET). METHODS: Forty-six consecutive patients were
      included in this study. Medical records were reviewed, and a follow-up
      questionnaire was sent to all surviving patients. RESULTS: Seventy percent of all
      possible participants (26 patients) answered the questionnaire. Follow-up time
      for the responding patients was median 6.0 years (2-16). Median self-reported
      score on visual analogue scale of the initial postoperative effect on tremor was
      8.5 (0.1-10), with a significant reduction to 7.4 (0-10) at follow-up (p =
      0.001). Patients reported a median score of 10 (0-10) for overall patient
      satisfaction with VIM-DBS treatment. Eight patients (17%) died after median 8.9
      years (0.6-15) after surgery, at median age 77.4 years (70-89). One patient (2%)
      committed suicide seven months after the operation. Calculated standard mortality
      ratio among ET patients was 1.3 (CI 0.6-2.6), similar to the general population.
      CONCLUSION: We found no significant increase in mortality in this cohort of VIM
      DBS operated ET patients compared to the general population in Norway. The
      patients reported high long-term satisfaction and continuing effect of VIM-DBS on
      tremor even after many years. VIM-DBS therefore seems to be an effective
      symptomatic long-term treatment of ET. However, one patient committed suicide.
      Only one other suicide has previously been reported after VIM-DBS. It is
      therefore still unclear whether VIM-DBS increases suicide risk.

PMID- 24903551
TI  - Sudden unexpected death in epilepsy: assessing the public health burden.
AB  - OBJECTIVE: There is not yet a clear consensus on the incidence of sudden
      unexpected death in epilepsy (SUDEP) or the extent of its burden on public
      health. In this systematic review, we seek to summarize the incidence of SUDEP
      and its age distribution, as well as the years of potential life lost and
      cumulative risks of SUDEP for persons with epilepsy. METHODS: We conducted a
      systematic search for epidemiologic studies of sudden death in epilepsy and rated
      their quality of evidence. We pooled data from comparable higher quality
      population-based studies of SUDEP incidence across all age groups, calculating
      the overall incidence of SUDEP per 100,000 population, and per 1,000 people with
      epilepsy. Using standard formulas, we also calculated the years of potential life
      lost and cumulative risks associated with SUDEP. RESULTS: SUDEP has an estimated
      overall crude annual incidence rate of 0.81 cases per 100,000 population, or 1.16
      cases per 1,000 patients with epilepsy. Comparing years of potential life lost
      from SUDEP with selected other neurologic diseases, SUDEP ranks second only to
      stroke. SIGNIFICANCE: Despite limitations to the data on which our analysis is
      based, we conclude that the public health burden of SUDEP, which has previously
      been underappreciated, is substantial and deserves much more attention from
      clinicians, researchers, and the public health community.

PMID- 24903552
TI  - Understanding melatonin receptor pharmacology: latest insights from mouse models,
      and their relevance to human disease.
AB  - Melatonin, the neuro-hormone synthesized during the night, has recently seen an
      unexpected extension of its functional implications toward type 2 diabetes
      development, visual functions, sleep disturbances, and depression. Transgenic
      mouse models were instrumental for the establishment of the link between
      melatonin and these major human diseases. Most of the actions of melatonin are
      mediated by two types of G protein-coupled receptors, named MT1 and MT2 , which
      are expressed in many different organs and tissues. Understanding the
      pharmacology and function of mouse MT1 and MT2 receptors, including MT1 /MT2
      heteromers, will be of crucial importance to evaluate the relevance of these
      mouse models for future therapeutic developments. This review will critically
      discuss these aspects, and give some perspectives including the generation of new
      mouse models. 

PMID- 24903555
TI  - Corrigendum.
AB  - The authors would like to bring attention to the error published in
      'Bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a
      fixed-combination syrup versus an oral reference product' 'Annick Janin and
      Joelle Monnet' Journal of International Medical Research 42(2) pp. 347-359. DOI:
      10.1177/0300060513503762. 

PMID- 24903553
TI  - Leucine-rich glioma inactivated 3 is a melanogenic cytokine in human skin.
AB  - Recently, we demonstrated that leucine-rich glioma inactivated 3 (LGI3) is
      expressed in human skin. However, the effects of LGI3 on melanocytes remain
      unknown. The present study demonstrated that LGI3 can serve to stimulate
      melanogenesis without affecting cell viability. To determine the effects of LGI3
      on melanin synthesis, normal human melanocytes and Mel-Ab cells were treated with
      recombinant LGI3 and melanin content was measured. Our results showed that LGI3
      promoted melanin synthesis in both cell types. Moreover, upregulation of
      microphthalmia-associated transcription factor (MITF) and tyrosinase was observed
      at both the mRNA and protein levels via RT-PCR and Western blotting,
      respectively. Furthermore, immunohistochemical staining showed that the
      expression of LGI3 increased in the basal layer of melasma skin samples, whereas
      it decreased slightly in vitiligo samples. These results suggest that LGI3 may
      play a role as a melanogenic cytokine in human skin. 

PMID- 24903554
TI  - The role of magnetic resonance diffusion-weighted imaging and three-dimensional
      arterial spin labelling perfusion imaging in the differentiation of parasellar
      meningioma and cavernous haemangioma.
AB  - OBJECTIVE: To evaluate the diagnostic value of magnetic resonance diffusion
      weighted imaging (DWI) and three-dimensional arterial spin labelling perfusion
      imaging (3D-ASL) in distinguishing cavernous haemangioma from parasellar
      meningioma, using histological data as a reference standard. METHODS: Patients
      with parasellar meningioma or parasellar cavernous haemangioma underwent
      conventional T1- and T2-weighted magnetic resonance imaging (MRI) followed by DWI
      and 3D-ASL using a 3.0 Tesla MRI. The minimum apparent diffusion coefficient
      (minADC) from DWI and the maximal normalized cerebral blood flow (nCBF) from 3D
      ASL were measured in each tumour. Diagnosis was confirmed by histology. RESULTS:
      MinADC was significantly lower and nCBF significantly higher in meningioma (n =
      19) than cavernous haemangioma (n = 15). There was a significant negative
      correlation between minADC and nCBF (r = -0.605). CONCLUSION: DWI and 3D-ASL are
      useful in differentiating cavernous haemangiomas from parasellar meningiomas,
      particularly in situations when the appearance on conventional MRI sequences is
      otherwise ambiguous.

PMID- 24903556
TI  - Role of bicyclol in preventing chemotherapeutic agent-induced liver injury in
      patients over 60 years of age with cancer.
AB  - OBJECTIVE: To evaluate the efficacy of bicyclol in preventing chemotherapy
      induced liver damage. METHODS: Patients >=60 years of age with cancer were
      equally randomized into control (chemotherapy alone) or prophylactic
      (chemotherapy supplemented with 75 mg bicyclol, oral, daily) groups. Liver
      function indices were assessed immediately before treatment, during each therapy
      cycle and following treatment. RESULTS: Of 306 patients enrolled, 300 patiets
      completed the study (n = 147 and n = 153; prophylactic and control groups,
      respectively). Incidence of grade I-IV elevation of serum transaminase and/or
      bilirubin was significantly lower in the prophylactic group (17.1%) compared with
      the control group (47.1%). Incidence of grade II-IV hepatic injury was also
      significantly lower in the prophylactic group (0.7%) than in the control group
      (12.4%). CONCLUSIONS: Prophylactic bicyclol (75 mg daily) could significantly
      reduce the incidence and degree of chemotherapeutic agent-induced liver damage in
      elderly patients with cancer. Further studies are recommended with larger sample
      sizes and long-term follow up.

PMID- 24903557
TI  - Cytokines in tears during the secondary keratoconjunctival responses induced by
      allergic reaction in the nasal mucosa.
AB  - BACKGROUND: Allergic keratoconjunctivitis (KC) can occur in a primary form due to
      an allergic reaction taking place in the conjunctivae or in a secondary form
      induced by nasal allergy. OBJECTIVES: To search for the cytokine changes in tears
      accompanying the secondary keratoconjunctival response types (SKCR), caused by
      the nasal allergy. METHODS: In 43 KC patients developing 15 immediate (SIKCR), 16
      late (SLKCR) and 12 delayed (SDYKCR) responses to nasal provocation tests with
      allergens (NPT), the NPTs were repeated with subsequent recording of cytokine
      concentrations in tears up to 72 h. RESULTS: The SIKCRs (p<0.001), occurring 10
      120 min after the NPT, were accompanied by significant changes (p<0.05) of
      interleukin (IL)-4, IL-6, IL-10, IL-12p70 and granulocyte-macrophage colony
      stimulating factor (GM-CSF). The SLKCRs (p<0.01), appearing 5-12 h after the NPT,
      were associated with significant changes (p<0.05) of IL-3, IL-4, IL-5, IL-8, IL
      10, tumor necrosis factor (TNF)-alpha, GM-CSF and granulocyte colony-stimulating
      factor. The SDYKCRs (p<0.01), occurring 24-48 h after the NPT, were accompanied
      by significant changes (p<0.05) of IL-2, IL-8, IL-10, interferon-gamma,
      transforming growth factor-beta and TNF-alpha. CONCLUSIONS: The particular SKCR
      types, induced by an allergic reaction in the nasal mucosa, were accompanied by
      different cytokine profiles in the tears, suggesting involvement of different
      hypersensitivity mechanisms. These results also stress the diagnostic usefulness
      of NPTs combined with monitoring of ocular features in KC patients who did not
      respond satisfactorily to the topical ophthalmological treatment.

PMID- 24903558
TI  - Long-term trends and outcomes of anterior vitrectomy in Western Australia.
AB  - PURPOSE: To describe trends, risk factors and outcomes of anterior vitrectomy
      during cataract and intraocular lens (IOL) surgery. METHODS: All patients 16
      years and older undergoing cataract and IOL surgery in Western Australia (WA)
      from January 1980 to December 2001 (n = 115 815) were included. Hospital
      administrative data were used to identify all cataract and IOL procedures and
      subsequent admissions for retinal detachment, IOL dislocation, endophthalmitis
      and pseudophakic corneal oedema. Data were validated with chart review and
      analysed to identify trends and risk factors for anterior vitrectomy and the risk
      of subsequent complications. RESULTS: In total, 1390 (1.2%) anterior vitrectomies
      were performed. The rate increased with change in surgical technique. Significant
      risk factors for anterior vitrectomy were age <50 years (OR 1.31), male sex (OR
      1.23), IOL procedure (OR 11.45) and operations in public hospitals (OR 1.99) or
      rural/remote (OR 1.40) areas. Anterior vitrectomy was strongly associated with
      increased risk of retinal detachment (RD) (RR 18.5), endophthalmitis (RR 3.6),
      IOL dislocation (RR 21.1) and pseudophakic corneal oedema (RR 17.3). Retinal
      detachments and IOL dislocations occur earlier after anterior vitrectomy.
      CONCLUSION: Anterior vitrectomy rates have remained stable since the introduction
      of phacoemulsification. Anterior vitrectomy is a major risk factor for serious
      complications compared with uncomplicated surgery, particularly RD and IOL
      dislocation. We identified an increasing trend in anterior vitrectomy being
      performed during extracapsular and IOL surgery.

PMID- 24903559
TI  - On the origin of grasshopper oviposition behavior: structural homology in
      pregenital and genital motor systems.
AB  - In female grasshoppers, oviposition is a highly specialized behavior involving a
      rhythm-generating neural circuit, the oviposition central pattern generator,
      unusual abdominal appendages, and dedicated muscles. This study of Schistocerca
      americana (Drury) grasshoppers was undertaken to determine whether the simpler
      pregenital abdominal segments, which do not contain ovipositor appendages, share
      common features with the genital segment, suggesting a roadmap for the genesis of
      oviposition behavior. Our study revealed that although 5 of the standard
      pregenital body wall muscles were missing in the female genital segment,
      homologous lateral nerves were, indeed, present and served 4 ovipositor muscles.
      Retrograde labeling of the corresponding pregenital nerve branches in male and
      female grasshoppers revealed motor neurons, dorsal unpaired median neurons, and
      common inhibitor neurons which appear to be structural homologues of those filled
      from ovipositor muscles. Some pregenital motor neurons displayed pronounced
      contralateral neurites; in contrast, some ovipositor motor neurons were
      exclusively ipsilateral. Strong evidence of structural homology was also obtained
      for pregenital and ovipositor skeletal muscles supplied by the identified neurons
      and of the pregenital and ovipositor skeletons. For example, transient embryonic
      segmental appendages were maintained in the female genital segments, giving rise
      to ovipositor valves, but were lost in pregenital abdominal segments. Significant
      proportional differences in sternal apodemes and plates were observed, which
      partially obscure the similarities between the pregenital and genital skeletons.
      Other changes in reorganization included genital muscles that displayed adult
      hypertrophy, 1 genital muscle that appeared to represent 2 fused pregenital
      muscles, and the insertion points of 2 ovipositor muscles that appeared to have
      been relocated. Together, the comparisons support the idea that the oviposition
      behavior of genital segments is built upon a homologous, segmentally iterated
      motor infrastructure located in the pregenital abdomen of male and female
      grasshoppers.

PMID- 24903560
TI  - Dual catalysis. Single-electron transmetalation in organoboron cross-coupling by
      photoredox/nickel dual catalysis.
AB  - The routine application of C(sp3)-hybridized nucleophiles in cross-coupling
      reactions remains an unsolved challenge in organic chemistry. The sluggish
      transmetalation rates observed for the preferred organoboron reagents in such
      transformations are a consequence of the two-electron mechanism underlying the
      standard catalytic approach. We describe a mechanistically distinct single
      electron transfer-based strategy for the activation of organoboron reagents
      toward transmetalation that exhibits complementary reactivity patterns.
      Application of an iridium photoredox catalyst in tandem with a nickel catalyst
      effects the cross-coupling of potassium alkoxyalkyl- and benzyltrifluoroborates
      with an array of aryl bromides under exceptionally mild conditions (visible
      light, ambient temperature, no strong base). The transformation has been extended
      to the asymmetric and stereoconvergent cross-coupling of a secondary
      benzyltrifluoroborate.

PMID- 24903561
TI  - Metamaterials. Invisibility cloaking in a diffusive light scattering medium.
AB  - In vacuum, air, and other surroundings that support ballistic light propagation
      according to Maxwell's equations, invisibility cloaks that are macroscopic, three
      dimensional, broadband, passive, and that work for all directions and
      polarizations of light are not consistent with the laws of physics. We show that
      the situation is different for surroundings leading to multiple light scattering,
      according to Fick's diffusion equation. We have fabricated cylindrical and
      spherical invisibility cloaks made of thin shells of polydimethylsiloxane doped
      with melamine-resin microparticles. The shells surround a diffusively reflecting
      hollow core, in which arbitrary objects can be hidden. We find good cloaking
      performance in a water-based diffusive surrounding throughout the entire visible
      spectrum and for all illumination conditions and incident polarizations of light.

PMID- 24903562
TI  - Screening for noise in gene expression identifies drug synergies.
AB  - Stochastic fluctuations are inherent to gene expression and can drive cell-fate
      specification. We used such fluctuations to modulate reactivation of HIV from
      latency-a quiescent state that is a major barrier to an HIV cure. By screening a
      diverse library of bioactive small molecules, we identified more than 80
      compounds that modulated HIV gene-expression fluctuations (i.e., "noise"),
      without changing mean expression. These noise-modulating compounds would be
      neglected in conventional screens, and yet, they synergized with conventional
      transcriptional activators. Noise enhancers reactivated latent cells
      significantly better than existing best-in-class reactivation drug combinations
      (and with reduced off-target cytotoxicity), whereas noise suppressors stabilized
      latency. Noise-modulating chemicals may provide novel probes for the
      physiological consequences of noise and an unexplored axis for drug discovery,
      allowing enhanced control over diverse cell-fate decisions. 

PMID- 24903563
TI  - Dual catalysis. Merging photoredox with nickel catalysis: coupling of alpha
      carboxyl sp3-carbons with aryl halides.
AB  - Over the past 40 years, transition metal catalysis has enabled bond formation
      between aryl and olefinic (sp(2)) carbons in a selective and predictable manner
      with high functional group tolerance. Couplings involving alkyl (sp(3)) carbons
      have proven more challenging. Here, we demonstrate that the synergistic
      combination of photoredox catalysis and nickel catalysis provides an alternative
      cross-coupling paradigm, in which simple and readily available organic molecules
      can be systematically used as coupling partners. By using this photoredox-metal
      catalysis approach, we have achieved a direct decarboxylative sp(3)-sp(2) cross
      coupling of amino acids, as well as alpha-O- or phenyl-substituted carboxylic
      acids, with aryl halides. Moreover, this mode of catalysis can be applied to
      direct cross-coupling of C(sp3)-H in dimethylaniline with aryl halides via C-H
      functionalization.

PMID- 24903564
TI  - Nutrition and training adaptations in aquatic sports.
AB  - The adaptive response to training is determined by the combination of the
      intensity, volume, and frequency of the training. Various periodized approaches
      to training are used by aquatic sports athletes to achieve performance peaks.
      Nutritional support to optimize training adaptations should take periodization
      into consideration; that is, nutrition should also be periodized to optimally
      support training and facilitate adaptations. Moreover, other aspects of training
      (e.g., overload training, tapering and detraining) should be considered when
      making nutrition recommendations for aquatic athletes. There is evidence, albeit
      not in aquatic sports, that restricting carbohydrate availability may enhance
      some training adaptations. More research needs to be performed, particularly in
      aquatic sports, to determine the optimal strategy for periodizing carbohydrate
      intake to optimize adaptations. Protein nutrition is an important consideration
      for optimal training adaptations. Factors other than the total amount of daily
      protein intake should be considered. For instance, the type of protein, timing
      and pattern of protein intake and the amount of protein ingested at any one time
      influence the metabolic response to protein ingestion. Body mass and composition
      are important for aquatic sport athletes in relation to power-to-mass and for
      aesthetic reasons. Protein may be particularly important for athletes desiring to
      maintain muscle while losing body mass. Nutritional supplements, such as b
      alanine and sodium bicarbonate, may have particular usefulness for aquatic
      athletes' training adaptation. 

PMID- 24903565
TI  - Cost savings using a protocol approach to manage anemia in a hemodialysis unit.
AB  - BACKGROUND: National guidelines recommend using anemia management protocols to
      guide treatment. The objective of this study was to determine if an anemia
      management protocol would improve hemoglobin (Hgb) indices in hemodialysis
      patients and to measure whether the protocol would reduce the use and cost of
      darbepoetin alfa (DBO) and intravenous (IV) iron in hemodialysis patients.
      METHODS: An anemia management protocol was created and implemented for
      hemodialysis patients at our institution. A retrospective observational review of
      the use of DBO and IV iron as well as changes in Hgb, transferrin saturation and
      ferritin in 174 patients was conducted 6 months before and after implementation
      of the anemia protocol. RESULTS: The number of Hgb measurements in the target
      range increased from 44.3 to 46.0% (p = 0.48) after protocol implementation. The
      mean weekly dose of DBO was reduced from 34.56 +/- 31.12 to 31.11 +/- 28.64 MUg
      post-protocol implementation (p = 0.011), which translated to a cost savings of
      USD 41,649 over 6 months. The mean monthly IV iron dose also decreased from
      139.56 +/- 98.83 to 97.65 +/- 79.05 mg (p < 0.005), a cost savings of USD 18,594
      over the same time period. CONCLUSION: The use of an anemia management protocol
      resulted in the deprescribing of DBO and iron agents while increasing the number
      of patients in the target Hgb range, which led to significant cost savings in the
      treatment of anemia.

PMID- 24903566
TI  - A new clinical scoring system to define pneumonia following esophagectomy for
      cancer.
AB  - BACKGROUND: Pneumonia is a frequently observed complication following
      esophagectomy. The lack of a uniform definition of pneumonia leads to large
      variations of pneumonia rates in literature. This study was designed to develop a
      scoring system for diagnosing pneumonia following esophagectomy at the hospital
      ward. METHODS: In a prospective cohort study of esophagectomy patients, known
      risk factors for pneumonia, temperature, leukocyte count, pulmonary radiography
      and sputum culture added were evaluated. Primary outcome was defined as the
      decision to treat suspected pneumonia. Multivariate Cox regression analysis with
      backward selection was used to identify predictors of pneumonia treatment.
      RESULTS: The majority of postoperative pneumonia treatments (88.2%) occurred at
      the hospital ward, where treatment was observed in 67 (36.2%) of 185 patients.
      Independent diagnostic determinants for pneumonia treatment were temperature
      (hazard ratio (HR) = 1.283, p = 0.073), leukocyte count (HR = 1.040, p = 0.078)
      and pulmonary radiography (HR >11.0, p = 0.000). Sputum culture did not influence
      the decision to treat pneumonia. These findings were used to develop a scoring
      system which includes temperature, leukocyte count and pulmonary radiography.
      CONCLUSION: The decision to treat pneumonia is based on temperature, leukocyte
      count and pulmonary radiography findings. The proposed clinical scoring system
      for pneumonia following esophagectomy at the hospital ward has the potential to
      aid clinical practice and improve comparability of future research in esophageal
      cancer surgery.

PMID- 24903567
TI  - Cyto-histopathological and outcome features of the prepuce squamous cell
      carcinoma of a mixed breed dog.
AB  - BACKGROUND: Squamous cell carcinomas (SCCs) are uncommon, high-grade tumors,
      predominantly composed of round cells in the prepuce. The aim of this study is to
      better define the clinicopathologic features of this neoplasm. CASE REPORT: We
      conducted cyto-histopathologic analysis on the manifestations of the prepuce SCC
      by H & E staining in a terrier mix dog. Grossly, tumor was large, multiple
      erythematous patch, and ulcerated masses frequently affecting the prepuce and
      deeply invading to distal prepuce out from the ventro-lateral of penis and the
      tumor covered by a necrotic discharge. Cytological evaluation of fine-needle
      aspirates from the cutaneous mass from the prepuce comprised of round nuclei,
      coarse chromatin pattern, distinct nucleoli and nuclear pleomorphism.
      Furthermore, the neoplastic cells were pleomorphic, round to caudate in shape,
      exhibiting prominent anisokaryosis and anisocytosis with rare mitotic features.
      Microscopically, the lesions were predominantly composed of atypical round cells
      disposed in interlacing fascicles. Frequent findings include keratin formation,
      horn pearls, mitoses and cellular atypia. The cells showed distinct borders,
      ranged from polygonal to round or elongate and had moderate amounts of
      eosinophilic cytoplasm. CONCLUSION: The histopathologic features coupled with the
      cytopathology findings led to a diagnosis of squamous cell carcinoma. To the
      authors' knowledge, this is the first time that multiple erythematous plaques
      have undergone malignant transformation in a terrier mix dog. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5748771971272873.

PMID- 24903568
TI  - Cytomegalovirus antiviral resistance: characterization of results from clinical
      specimens.
AB  - BACKGROUND: Cytomegalovirus (CMV) infections are a major cause of disease among
      immunocompromised patients. Prolonged antiviral therapy is often necessary to
      prevent or treat CMV disease, and may lead to development of antiviral resistance
      (AVR). Timely identification of viral mutations conferring resistance is
      essential for effective patient management. METHODS: Amplification by polymerase
      chain reaction followed by bi-directional nucleotide sequencing was performed for
      relevant regions of the CMV UL97 and UL54 genes. Results from 570 samples
      submitted to a commercial reference laboratory for testing were reviewed and
      characterized with respect to the frequency of mutations detected, association
      with viral load (VL), and consistency of results in a subset of patients with
      multiple samples. Only AVR mutations confirmed by marker transfer experiments
      were included in the analysis. RESULTS: AVR mutations were identified in 176
      (30.9%) of the 570 samples evaluated. A total of 17 different UL97 mutations and
      29 different UL54 mutations were detected. A single mutation per sample was most
      commonly observed, although 61 samples (10.7%) had >1 mutation, with 40 samples
      (7.0%) having mutations in both UL97 and UL54 genes. The VL of samples with AVR
      mutations ranged from 2.03-7.15 log10 copies/mL, and the VL did not differ
      significantly from samples without AVR mutations. A subset of patients (N = 85)
      had >1 sample tested, and 48.2% of these patients returned the same result for
      each sample analyzed, while the remainder had a different results. CONCLUSIONS:
      Genomic mutations conferring resistance in CMV to antiviral drugs were commonly
      identified in samples submitted from clinical patients to a reference laboratory
      for AVR testing. Mutations were identified over the full range of VLs and no
      correlation was identified between VL and the presence of AVR mutations. In
      patients with multiple samples submitted for analysis, approximately half of the
      patients had samples with variable results when the initial result was compared
      to subsequent results.

PMID- 24903569
TI  - Closantel plasma and milk disposition in dairy goats: assessment of drug residues
      in cheese and ricotta.
AB  - Closantel (CLS) is currently used in programs for the strategic control of
      gastrointestinal nematodes. CLS is extralabel used in different dairy goat
      production systems. From available data in dairy cows, it can be concluded that
      residues of CLS persist in milk. The current work evaluated the concentration
      profiles of CLS in plasma and milk from lactating orally treated dairy goats to
      assess the residues pattern in dairy products such as cheese and ricotta. Six (6)
      female Saanen dairy goats were treated orally with CLS administered at 10 mg/kg.
      Blood and milk samples were collected between 0 and 36 days post-treatment. The
      whole milk production was collected at 1, 4, 7, and 10 days post-treatment to
      produce soft cheese and ricotta. CLS concentrations in plasma, milk, cheese,
      whey, and ricotta were determined by HPLC. The concentrations of CLS measured in
      plasma were higher than those measured in milk at all sampling times. However,
      the calculated withdrawal time for CLS in milk was between 39 and 43 days
      postadministration to dairy goats. CLS residual concentrations in cheese (between
      0.93 and 1.8 MUg/g) were higher than those measured in the milk used for its
      production. CLS concentrations in ricotta were sixfold higher than those in the
      milk and 20-fold higher than those in the whey used for its production. The
      persistent and high residual concentrations of CLS in the milk and in the cheese
      and ricotta should be seriously considered before issuing any recommendation on
      the extralabel use of CLS in dairy goat farms. 

PMID- 24903570
TI  - Stroke in the rain forest: prevalence in a ribeirinha community and an urban
      population in the Brazilian Amazon.
AB  - BACKGROUND: Our objective was to determine the cerebrovascular prevalence in a
      town in the Brazilian Amazon basin and compare the ribeirinhos (riparians) to the
      urban population in the same municipality. METHODS: From May to October 2011,
      6,216 residents over 35 years of age in the town of Coari were interviewed using
      a screening questionnaire, the Stroke Symptom Questionnaire. Cerebrovascular
      prevalence rates (PRs) from the door-to-door surveillance were calculated
      according to the location of the home. RESULTS: Respondent totals were 4,897 in
      the urban area and 1,028 in the rural area. The crude prevalence of stroke was
      6.3% in rural and 3.7% in urban areas with differences maintained after sex and
      age adjustment. Among stroke cases, the ribeirinhos were those with less access
      to medical care in comparison to the urban area (32.1 vs. 52.5%, p = 0.01), and a
      positive association between rural area and no medical care for stroke remained
      (PR, 1.33; 95% confidence interval, 1.03-1.71), independently of age, sex,
      education and functional impairment. CONCLUSIONS: This study provides the first
      population-based cerebrovascular prevalence comparison between an urban and a
      rural population in the Amazon rain forest. The PRs were higher in the ribeirinha
      compared to the urban population in the same municipality.

PMID- 24903571
TI  - Ruderman-Kittel-Kasuya-Yosida interaction in silicene.
AB  - We investigate the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction between two
      magnetic impurities in a monolayer silicene. Due to spin-orbit (SO) coupling, the
      RKKY interaction can be further divided into various types according to the
      polarization directions of the magnetic impurities. We demonstrate that the
      spatial behaviors of the RKKY interaction closely relate to the external electric
      field, which together with the SO coupling gives rise to various phases in
      undoped silicene. Consequently, by probing the RKKY interaction, which contains
      all the information in the momentum space, differences between the topological
      phase and the trivial phase can be identified explicitly. Moreover, the change of
      chemical potential induced by the doping of silicene can also have a profound
      influence on the spatial behaviors of the RKKY interaction. 

PMID- 24903572
TI  - Configurations and control of magnetic fields for manipulating magnetic particles
      in microfluidic applications: magnet systems and manipulation mechanisms.
AB  - The use of a magnetic field for manipulating the motion of magnetic particles in
      microchannels has attracted increasing attention in microfluidic applications.
      Generation of a flexible and controllable magnetic field plays a crucial role in
      making better use of the particle manipulation technology. Recent advances in the
      development of magnet systems and magnetic field control methods have shown that
      it has great potential for effective and accurate manipulation of particles in
      microfluidic systems. Starting with the analysis of magnetic forces acting on the
      particles, this review gives the configurations and evaluations of three main
      types of magnet system proposed in microfluidic applications. The interaction
      mechanisms of magnetic particles with magnetic fields are also discussed. 

PMID- 24903573
TI  - A self-assembled conformational switch: a host-guest stabilized triple stem
      molecular beacon via a photoactivated and thermal regeneration mode.
AB  - We present a novel strategy for construction of a conformational switch of a
      molecular beacon based on the combination of nucleic acid (DNA) self-assembly and
      reversible host-guest inclusion interaction. With the functionalized probe, the
      nucleic acid hybridization process can be easily controlled with a photoactivated
      and thermal regeneration mode. 

PMID- 24903574
TI  - Learning the preferences of physicians for the organization of result lists of
      medical evidence articles.
AB  - BACKGROUND: Online medical knowledge repositories such as MEDLINE and The
      Cochrane Library are increasingly used by physicians to retrieve articles to aid
      with clinical decision making. The prevailing approach for organizing retrieved
      articles is in the form of a rank-ordered list, with the assumption that the
      higher an article is presented on a list, the more relevant it is. OBJECTIVES:
      Despite this common list-based organization, it is seldom studied how physicians
      perceive the association between the relevance of articles and the order in which
      articles are presented. In this paper we describe a case study that captured
      physician preferences for 3-element lists of medical articles in order to learn
      how to organize medical knowledge for decision-making. METHODS: Comprehensive
      relevance evaluations were developed to represent 3-element lists of hypothetical
      articles that may be retrieved from an online medical knowledge source such as
      MEDLINE or The Cochrane Library. Comprehensive relevance evaluations asses not
      only an article's relevance for a query, but also whether it has been placed on
      the correct list position. In other words an article may be relevant and
      correctly placed on a result list (e.g. the most relevant article appears first
      in the result list), an article may be relevant for a query but placed on an
      incorrect list position (e.g. the most relevant article appears second in a
      result list), or an article may be irrelevant for a query yet still appear in the
      result list. The relevance evaluations were presented to six senior physicians
      who were asked to express their preferences for an article's relevance and its
      position on a list by pairwise comparisons representing different combinations of
      3-element lists. The elicited preferences were assessed using a novel GRIP
      (Generalized Regression with Intensities of Preference) method and represented as
      an additive value function. Value functions were derived for individual
      physicians as well as the group of physicians. RESULTS: The results show that
      physicians assign significant value to the 1st position on a list and they expect
      that the most relevant article is presented first. Whilst physicians still prefer
      obtaining a correctly placed article on position 2, they are also quite satisfied
      with misplaced relevant article. Low consideration of the 3rd position was
      uniformly confirmed. CONCLUSIONS: Our findings confirm the importance of placing
      the most relevant article on the 1st position on a list and the importance paid
      to position on a list significantly diminishes after the 2nd position. The
      derived value functions may be used by developers of clinical decision support
      applications to decide how best to organize medical knowledge for decision making
      and to create personalized evaluation measures that can augment typical measures
      used to evaluate information retrieval systems.

PMID- 24903578
TI  - [Cognitive stimulation and music intervention for people with dementia in nursing
      homes: A pilot study, problems and perspectives].
AB  - BACKGROUND: Nonpharmacological interventions in people with dementia are becoming
      an increasingly important addition to pharmacological therapy. However, the
      current state of research in this field is limited. OBJECTIVES: The aim of this
      pilot study was to evaluate the effects of a cognitive stimulation program and a
      music intervention program on cognitive function, quality of life and activities
      of daily living in persons with dementia residing in nursing homes. In addition,
      specific challenges of randomized controlled trials in nursing homes should be
      identified to define recommendations for further studies. METHODS: Over a period
      of 6 weeks, 24 individuals with mild to moderate dementia were randomly allocated
      to participation in a cognitive stimulation program or in a music intervention.
      Each program consisted of twelve group-sessions of 90 min with two sessions per
      week. A neuropsychological test battery was performed before and after the
      training period. RESULTS: There were no significant improvements on the group
      level. In fact, performance declined in some domains. Nonetheless, heterogeneous
      results were evident in both groups after analysis on a single-case approach and
      some persons significantly improved their performance. CONCLUSION: At least on a
      single-case approach, the study provides additional support for the potential of
      nonpharmacological interventions. Future studies should target logistical aspects
      in nursing homes, realistic planning of sample size, formulating adequate
      inclusion and exclusion criteria, and choosing suitable neuropsychological tests.

PMID- 24903577
TI  - Angiopoietin-like 4 stimulates STAT3-mediated iNOS expression and enhances
      angiogenesis to accelerate wound healing in diabetic mice.
AB  - Impaired wound healing is a major source of morbidity in diabetic patients. Poor
      outcome has, in part, been related to increased inflammation, poor angiogenesis,
      and deficiencies in extracellular matrix components. Despite the enormous impact
      of these chronic wounds, effective therapies are lacking. Here, we showed that
      the topical application of recombinant matricellular protein angiopoietin-like 4
      (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by
      improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound
      injury. In contrast, ANGPTL4 expression remains low throughout the healing period
      in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks
      involved in cell migration, angiogenesis, and inflammation, as evidenced by an
      altered gene expression signature. ANGPTL4 influenced the expression profile of
      endothelial-specific CD31 in diabetic wounds, returning its profile to that
      observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production
      through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide
      synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown
      mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial
      cell communication. These data show that the replacement of ANGPTL4 may be an
      effective adjunctive or new therapeutic avenue for treating poor healing wounds.
      The present finding also confirms that therapeutic angiogenesis remains an
      attractive treatment modality for diabetic wound healing. 

PMID- 24903579
TI  - X-ray phase-contrast imaging at 100 keV on a conventional source.
AB  - X-ray grating interferometry is a promising imaging technique sensitive to
      attenuation, refraction and scattering of the radiation. Applications of this
      technique in the energy range between 80 and 150 keV pose severe technical
      challenges, and are still mostly unexplored. Phase-contrast X-ray imaging at such
      high energies is of relevant scientific and industrial interest, in particular
      for the investigation of strongly absorbing or thick materials as well as for
      medical imaging. Here we show the successful implementation of a Talbot-Lau
      interferometer operated at 100 keV using a conventional X-ray tube and a compact
      geometry, with a total length of 54 cm. We present the edge-on illumination of
      the gratings in order to overcome the current fabrication limits. Finally, the
      curved structures match the beam divergence and allow a large field of view on a
      short and efficient setup. 

PMID- 24903580
TI  - Magnetic resonance spectroscopy markers of axons and astrogliosis in relation to
      specific features of white matter injury in preterm infants.
AB  - INTRODUCTION: Punctate white matter lesions (pWMLs) and diffuse excessive high
      signal intensity (DEHSI) are commonly observed signal abnormalities on MRI scans
      of high-risk preterm infants near term-equivalent age. To establish whether these
      features are indicative abnormalities in axonal development or astroglia, we
      compared pWMLs and DEHSI to markers of axons and astrogliosis, derived from
      magnetic resonance spectroscopy (MRS). METHODS: Data from 108 preterm infants
      (gestational age at birth 31.0 weeks +/- 4.3; age at scan 41.2 weeks +/- 6.0) who
      underwent MR examinations under clinical indications were included in this study.
      Linear regression analyses were used to test the effects of pWMLs and DEHSI on N
      acetyl-aspartate (NAA) and myoinositol concentrations, respectively. RESULTS:
      Across the full sample, pWMLs were associated with a reduction in NAA whereas
      moderate to severe DEHSI altered the normal age-dependent changes in myoinositol
      such that myoinositol levels were lower at younger ages with no change during the
      perinatal period. Subgroup analyses indicated that the above associations were
      driven by the subgroup of neonates with both pWMLs and moderate to severe DEHSI.
      CONCLUSION: Overall, these findings suggest that pWMLs in conjunction with
      moderate/severe DEHSI may signify a population of infants at risk for long-term
      adverse neurodevelopmental outcome due to white matter injury and associated
      axonopathy. The loss of normal age-associated changes in myoinositol further
      suggests disrupted astroglial function and/or osmotic dysregulation.

PMID- 24903581
TI  - Prolonged Curvularia endophthalmitis due to organism sequestration.
AB  - IMPORTANCE: Endophthalmitis caused by Curvularia is a rare condition seen after
      cataract surgery and trauma. The clinical course has not been described
      previously. OBJECTIVE: To examine the clinical course of 6 postoperative and
      trauma-related cases of Curvularia endophthalmitis. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective case series. We reviewed the archives of the
      microbiology laboratory of Bascom Palmer Eye Institute, a tertiary referral
      hospital, from January 1, 1980, through September 30, 2013, to identify cases of
      Curvularia endophthalmitis. Data collected included demographic information, the
      cause of endophthalmitis, presenting features, treatment course, the number of
      recurrences, the area of organism sequestration, and final visual outcome.
      EXPOSURES: Trauma and cataract surgery. MAIN OUTCOMES AND MEASURES: Times from
      the inciting event to presentation of symptoms, diagnosis, and eradication;
      visual acuity; and identification of the area of sequestration. RESULTS: We
      identified 6 patients with Curvularia endophthalmitis, including 5 who underwent
      cataract surgery and 1 after trauma. The diagnosis was established rapidly in the
      trauma case. In the postoperative cases, the time from the surgery to first
      symptoms ranged from 2 to 5 months; from the surgery to correct diagnosis, 7 to
      24 months; and from the surgery to eradication, 8 to 27 months. Despite
      aggressive antifungal therapy, eradication of the infection could be achieved
      only by identification and removal of the nidus of sequestration. The median
      follow-up was 29.5 months. CONCLUSIONS AND RELEVANCE: In cases of endophthalmitis
      caused by Curvularia, the diagnosis and treatment are often delayed, especially
      in postoperative cases. The eradication of the organism requires identification
      and removal of the nidi of sequestration.

PMID- 24903582
TI  - Incidental Cystic Lesions in the Pancreas: Resect? EUS? Follow?
AB  - OPINION STATEMENT: Pancreatic cysts challenge clinicians due to their increased
      incidental identification on radiology imaging, the limitations of currently
      available diagnostic tools, and potential for malignancy. Following initial
      identification of an incidental pancreatic cyst, a dedicated pancreatic protocol
      abdominal CT scan or MRI pancreas with MRCP should be performed. Surgical
      resection is recommended for all surgical candidates with MD-IPMN, mixed or
      combined type IPMN, mucinous cystic neoplasm, and solid pseudopapillary neoplasm.
      Serous cystadenoma may be followed with serial imaging unless the patient
      develops symptoms, the cyst is larger than 4 cm or rapidly growing, or diagnostic
      uncertainty remains despite thorough evaluation. Surveillance is also recommended
      for BD-IPMN without the following features concerning malignancy: obstructive
      jaundice with a cyst in the head of the pancreas; solid component; nodule; main
      pancreatic duct >=10 mm; or cytology suspected or positive for malignancy. BD
      IPMN >=3 cm without concerning features may also be followed carefully, although
      surgical resection should be considered in surgically fit patients. EUS-FNA for
      cyst wall cytology, CEA, amylase, and occasionally k-ras mutation are also likely
      aids in the diagnosis of pancreatic cysts beyond radiologic imaging. This author
      typically recommends EUS-FNA to further evaluate cysts larger than 1 cm without
      definitive indication for resection. EUS is also appropriate in patients with
      solid component, nodule, or size >=3 cm to aid in decision making, especially in
      older patients who may be less suitable surgical candidates. A multidisciplinary
      approach with a team of dedicated gastrointestinal radiologists, pancreatic
      surgeons, gastrointestinal pathologists, and gastroenterologists is essential for
      managing patients with pancreatic cysts.

PMID- 24903583
TI  - Predictable chaos: a review of the effects of emotions on attention, memory and
      decision making.
AB  - Healthcare practice and education are highly emotional endeavors. While this is
      recognized by educators and researchers seeking to develop interventions aimed at
      improving wellness in health professionals and at providing them with skills to
      deal with emotional interpersonal situations, the field of health professions
      education has largely ignored the role that emotions play on cognitive processes.
      The purpose of this review is to provide an introduction to the broader field of
      emotions, with the goal of better understanding the integral relationship between
      emotions and cognitive processes. Individuals, at any given time, are in an
      emotional state. This emotional state influences how they perceive the world
      around them, what they recall from it, as well as the decisions they make. Rather
      than treating emotions as undesirable forces that wreak havoc on the rational
      being, the field of health professions education could be enriched by a greater
      understanding of how these emotions can shape cognitive processes in increasingly
      predictable ways. 

PMID- 24903584
TI  - The Bias in researching cognitive bias.

PMID- 24903586
TI  - Pan-metazoan phylogeny of the DMRT gene family: a framework for functional
      studies.
AB  - The family of Doublesex-Mab-3 Related Transcription factors (DMRTs) includes key
      regulators of sexual differentiation and neurogenesis. To help understand the
      functional diversification of this gene family, we examined DMRT gene complements
      from the whole genome sequences and predicted gene models of 32 animal species
      representing 12 different phyla and from several non-metazoan outgroups. DMRTs
      are present in all animals except the sponge Amphimedon queenslandica, but are
      not found in any of the outgroups, indicating that this gene family is specific
      to animals and has an ancient pre-eumetazoan origin. Our analyses suggest that
      DMRT genes diversified independently in bilaterian and non-bilaterian animals.
      Most clades in the DMRT gene tree, including those containing the well
      characterized DMRT1 and doublesex genes, have phylogenetically limited
      distributions. 

PMID- 24903585
TI  - Verification of accurate technical insight: a prerequisite for self-directed
      surgical training.
AB  - Simulation-based surgical skills training during preclinical education is a
      persistent challenge due to time constraints of trainees and instructors alike.
      Self-directed practice is resource-efficient and flexible; however, insight into
      technical proficiency among trainees is often lacking. The purpose of this study
      is to prospectively assess the accuracy of self-assessments among medical
      students learning basic surgical suturing. Over seven weekly practice sessions,
      preclinical medical students performed serial repetitions of a simulation-based
      suturing task under one-on-one observation by one of four trainers. Following
      each task repetition, self- and trainer-assessments (SA-TA) were performed using
      a 36-point weighted checklist of technical standards developed a priori by expert
      consensus. Upon study completion, agreement between SA and TA was measured using
      weighted Cohen's kappa coefficients. Twenty-nine medical students each performed
      a median of 25 suture task repetitions (IQR 21.5-28). Self-assessments tended to
      overestimate proficiency during the first tertile of practice attempts. Agreement
      between SA and TA improved with experience, such that the weighted kappa
      statistics for the two-handed and instrument ties were >0.81 after 18-21 task
      attempts. Inexperienced trainees frequently overestimate technical proficiency
      through self-assessments. However, this bias diminishes with repetitive practice.
      Only after trainees have attained the capacity to accurately self-assess can
      effective self-directed learning take place. 

PMID- 24903587
TI  - Religiosity and Proactive Coping with Social Difficulties in Romanian
      Adolescents.
AB  - Even though medical and psychological sciences and services evolved so much, in
      many cases, the healing process has its mystery, and some recoveries seem to be
      entirely magical. Especially in such cases, religion seems to play an important
      role, as it helps people face the "mystery" of the healing process and integrate
      it. Religion has helped people face potentially traumatic events with minimum
      consequences for their health, or, moreover, to use these experiences for
      personal development, making them more prepared for life challenges. Adolescents
      with developed proactive coping skills are less socially inhibited or non
      assertive, and those that are less cold/distant or more self-sacrificing have
      stronger spiritual values. 

PMID- 24903589
TI  - Chromogranin-A levels measured with automated immunoassay.
AB  - Measurement of chromogranin-A (CgA) levels is relevant for the diagnosis of
      neuroendocrine neoplasms. The use of CgA testing for risk stratification of
      cardiovascular diseases is also increasing. The objective of our study was to
      determine the performances and reference values of a novel automated assay for
      CgA testing. The new method was compared with an enzyme-linked immunosorbent
      assay. Our results showed that the performances of the automated assay were
      satisfactory and that the agreement between the two methods was excellent. The
      automation of CgA testing also reduced the turnaround time of analysis and,
      therefore, might contribute to a faster delivery of the results to physicians. 

PMID- 24903590
TI  - Hippocampal proteoglycans brevican and versican are linked to spatial memory of
      Sprague-Dawley rats in the morris water maze.
AB  - Proteoglycans (PGs) are major constituents of the extracellular matrix and have
      recently been proposed to contribute to synaptic plasticity. Hippocampal PGs have
      not yet been studied or linked to memory. The aim of the study, therefore, was to
      isolate and characterize rat hippocampal PGs and determine their possible role in
      spatial memory. PGs were extracted from rat hippocampi by anion-exchange
      chromatography and analyzed by nano LC-MS/MS. Twenty male Sprague-Dawley rats
      were tested in the morris water maze. PGs agrin, amyloid beta A4 protein,
      brevican, glypican-1, neurocan, phosphacan, syndecan-4, and versican were
      identified in the hippocampi. Brevican and versican levels in the membrane
      fraction were higher in the trained group, correlating with the time spent in the
      target quadrant. alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor
      GluR1 was co-precipitated with brevican and versican. Levels for a receptor
      complex containing GluR1 was higher in trained while GluR2 and GluR3-containing
      complex levels were higher in yoked rats. The findings provide information about
      the PGs present in the rat hippocampus, demonstrating that versican and brevican
      are linked to memory retrieval in the morris water maze and that PGs interact
      with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor GluR1, which
      is linked to memory retrieval. Proteoglycans (PGs) are major constituents of the
      extracellular matrix of the brain and were proposed to contribute to synaptic
      plasticity. This report addressed PGs in rat hippocampus and suggests that PGs
      brevican and versican are linked to spatial memory, and form a complex with the
      GluR1 subunit of the AMPA receptor, a key signaling molecule in memory
      mechanisms. 

PMID- 24903591
TI  - Agroinfection of sweet potato by vacuum infiltration of an infectious
      sweepovirus.
AB  - Sweepovirus is an important monopartite begomovirus that infects plants of the
      genus Ipomoea worldwide. Development of artificial infection methods for
      sweepovirus using agroinoculation is a highly efficient means of studying
      infectivity in sweet potato. Unlike other begomoviruses, it has proven difficult
      to infect sweet potato plants with sweepoviruses using infectious clones. A novel
      sweepovirus, called Sweet potato leaf curl virus-Jiangsu (SPLCV-JS), was recently
      identified in China. In addition, the infectivity of the SPLCV-JS clone has been
      demonstrated in Nicotiana benthamiana. Here we describe the agroinfection of the
      sweet potato cultivar Xushu 22 with the SPLCV-JS infectious clone using vacuum
      infiltration. Yellowing symptoms were observed in newly emerged leaves. Molecular
      analysis confirmed successful inoculation by the detection of viral DNA. A
      synergistic effect of SPLCV-JS and the heterologous betasatellite DNA-beta of
      Tomato yellow leaf curl China virus isolate Y10 (TYLCCNV-Y10) on enhanced symptom
      severity and viral DNA accumulation was confirmed. The development of a routine
      agroinoculation system in sweet potato with SPLCV-JS using vacuum infiltration
      should facilitate the molecular study of sweepovirus in this host and permit the
      evaluation of virus resistance of sweet potato plants in breeding programs. 

PMID- 24903592
TI  - Simultaneous detection of duck hepatitis A virus types 1 and 3, and of duck
      astrovirus type 1, by multiplex RT-PCR.

PMID- 24903593
TI  - Critical role of Dengue Virus NS1 protein in viral replication.
AB  - Dengue virus (DENV) nonstructural protein 1 (NS1) is a highly conserved 46-kDa
      protein that contains 2 glycosylation sites (Asn-130 and Asn-207) and 12
      conserved cysteine (Cys) residues. Here, we performed site-directed mutagenesis
      to generate systematic mutants of viral strain TSV01. The results of the
      subsequent analysis showed that an alanine substitution at the second N-linked
      glycan Asn-207 in NS1 delayed viral RNA synthesis, reduced virus plaque size, and
      weakened the cytopathic effect. Three mutants at Cys sites (Cys-4, Cys-55, Cys
      291) and a C-terminal deletion (DeltaC) mutant significantly impaired RNA
      synthesis, and consequently abolished viral growth, whereas alanine mutations at
      Asn-130 and Glu-173 resulted in phenotypes that were similar to the wild-type
      (WT) virus. Further analysis showed that the Asn-207 mutation slightly delayed
      viral replication. These results suggest that the three conserved disulfide bonds
      and the second N-linked glycan in NS1 are required for DENV-2 replication. 

PMID- 24903594
TI  - Clarification of the terminology of the major human salivary glands: acinus and
      alveolus are not synonymous.
AB  - Discrepancies in the terminology of the major human salivary glands often appear
      in anatomical textbooks and tend to adversely affect student's learning
      experience in Microscopic Anatomy. The main culprit is the inconsistent
      description of the morphology of these glands secretory end pieces where "acinus"
      and "alveolus" are used interchangeably. The correct terminology originated from
      Malpighi (1687), repeated by Kolliker (1854), but over the years has been
      misinterpreted by prominent authors as a result of the nature of specimen
      preparation. This commentary is based on etymology, current standard light
      microscopy, research studies and consultation with experts. The overall objective
      of this publication is to recommend that textbooks should endeavour to modify the
      relevant descriptions about this terminology in their future editions. The most
      appropriate terminology for the major human salivary glands would be: (1) the
      parotid gland, entirely serous, should be called compound acinar glands; (2) the
      submandibular glands are mixed glands; their serous components are compound
      acinar while some of the mucinous areas are tubular with serous, crescents or
      demilunes, as acinar end pieces hence they should be named compound tubuloacinar
      glands; (3) the sublingual glands, mainly mucous glands with tubular shape, with
      small acinar end pieces that are serous crescents thence they should be called
      compound tubuloacinar glands.

PMID- 24903595
TI  - [Surgical treatment of acetabulum fractures in the elderly. Osteosynthesis or
      endoprosthesis].
AB  - BACKGROUND: Anatomical reconstruction of acetabulum fractures and rigid
      osteosynthesis are required to achieve good postoperative results. In the 7(th)
      decade of life changes of bone quality impair stability of fixation devices in
      bone. PATIENTS AND METHODS: This retrospective study evaluates and compares
      results of osteosynthesis and implantation of total hip arthroplasty in patients
      with acetabulum fractures. A total of 24 patients older than 65 years who
      sustained acetabular fractures type A, B and C according to AO classification
      were examined using several clinical measurements. Different scores for physical
      function, pain, general health and subjective assessment including psychosocial
      aspects were used. The outcome criteria were evaluated 1.5-10 years after
      surgery. RESULTS: Good reconstruction of the acetabulum was only achieved in 40 %
      of patients which corresponded with radiological long-term results. Pain relief
      and mobility were slightly better in patients who received primary
      alloarthroplasty of the hip joint, and periarticular ossification was observed
      more frequently following osteosynthesis. Surgical revisions were necessary more
      often after osteosynthesis of the acetabulum. The small number of cases showed no
      significant differences. The functional outcome did not show significant
      differences between primary alloarthroplasty and reconstruction of the
      acetabulum. CONCLUSION: Primary implantation with alloarthroplasty of the hip
      joint in case of a complex fracture of the acetabulum can be recommended for
      elderly patients if an anatomic or good reconstruction of the hip joint cannot be
      achieved.

PMID- 24903596
TI  - Repetitive systemic morphine alters activity-dependent plasticity of Schaffer
      collateral-CA1 pyramidal cell synapses: involvement of adenosine A1 receptors and
      adenosine deaminase.
AB  - The effectiveness of O-pulse stimulation (TPS) for the reversal of O-pattern
      primed bursts (PB)-induced long-term potentiation (LTP) were examined at the
      Schaffer-collateral-CA1 pyramidal cell synapses of hippocampal slices derived
      from rats chronically treated with morphine (M-T). The results showed that slices
      derived from both control and M-T rats had normal field excitatory postsynaptic
      potential (fEPSP)-LTP, whereas PS-LTP in slices from M-T rats was significantly
      greater than that from control slices. When morphine was applied in vitro to
      slices derived from rats chronically treated with morphine, the augmentation of
      PS-LTP was not seen. TPS given 30 min after LTP induction failed to reverse the
      fEPSP- or PS-LTP in both groups of slices. However, TPS delivered in the presence
      of long-term in vitro morphine caused the PS-LTP reversal. This effect was
      blocked by the adenosine A1 receptor (A1R) antagonist CPX (200 nM) and
      furthermore was enhanced by the adenosine deaminase (ADA) inhibitor EHNA (10
      MUM). Interestingly, TPS given 30 min after LTP induction in the presence of EHNA
      (10 MUM) can reverse LTP in morphine-exposed control slices in vitro. These
      results suggest adaptive changes in the hippocampus area CA1 in particular in
      adenosine system following repetitive systemic morphine. Chronic in vivo morphine
      increases A1R and reduces ADA activity in the hippocampus. Consequently,
      adenosine can accumulate because of a stimulus train-induced activity pattern in
      CA1 area and takes the opportunity to work as an inhibitory neuromodulator and
      also to enable CA1 to cope with chronic morphine. In addition, adaptive
      mechanisms are differentially working in the dendrite layer rather than the
      somatic layer of hippocampal CA1.

PMID- 24903597
TI  - Feature-positive discriminations during a spatial-search task with humans.
AB  - During feature-positive operant discriminations, a conditional cue, X, signals
      whether responses made during a second stimulus, A, are reinforced. Few studies
      have examined how landmarks, which can be trained to control the spatial
      distribution of responses during search tasks, might operate under conditional
      control. We trained college students to search for a target hidden on a computer
      monitor. Participants learned that responses to a hidden target location signaled
      by a landmark (e.g., A) would be reinforced only if the landmark was preceded by
      a colored background display (e.g., X). In Experiment 1, participants received
      feature-positive training (+<-YB/ XA->+/A-/B-) with the hidden target to the
      right of A and to left of B. Responding during nonreinforced transfer test trials
      (XB-/YA-) indicated conditional control by the colored background, and spatial
      accuracy indicated a greater weighting of spatial information provided by the
      landmark than by the conditional cue. In Experiments 2a and 2b, the location of
      the target relative to landmark A was conditional on the colored background (+<
      YA/ XA->+/ ZB->+/ +<-C /A-/B-). At test, conditional control and a greater
      weighting for the landmark's spatial information were again found, but we also
      report evidence for spatial interference by the conditional stimulus. Overall, we
      found that hierarchical accounts best explain the observed differences in
      response magnitude, whereas spatial accuracy was best explained via spatial
      learning models that emphasize the reliability, stability, and proximity of
      landmarks to a target.

PMID- 24903598
TI  - Social and nonsocial category discriminations in a chimpanzee (Pan troglodytes)
      and American black bears (Ursus americanus).
AB  - One captive adult chimpanzee and 3 adult American black bears were presented with
      a series of natural category discrimination tasks on a touch-screen computer.
      This is the first explicit comparison of bear and primate abilities using
      identical tasks, and the first test of a social concept in a carnivore. The
      discriminations involved a social relationship category (mother/offspring) and a
      nonsocial category involving food items. The social category discrimination could
      be made using knowledge of the overarching mother/offspring concept, whereas the
      nonsocial category discriminations could be made only by using perceptual rules,
      such as "choose images that show larger and smaller items of the same type." The
      bears failed to show above-chance transfer on either the social or nonsocial
      discriminations, indicating that they did not use either the perceptual rule or
      knowledge of the overarching concept of mother/offspring to guide their choices
      in these tasks. However, at least 1 bear remembered previously reinforced stimuli
      when these stimuli were recombined, later. The chimpanzee showed transfer on a
      control task and did not consistently apply a perceptual rule to solve the
      nonsocial task, so it is possible that he eventually acquired the social concept.
      Further comparisons between species on identical tasks assessing social knowledge
      will help illuminate the selective pressures responsible for a range of social
      cognitive skills.

PMID- 24903599
TI  - Transcatheter occlusion of azygos/hemiazygos vein in patients with systemic
      venous collateral development after the bidirectional Glenn procedure.
AB  - OBJECTIVES: To elucidate the feasibility and treatment effects of transcatheter
      occlusion of the azygos/hemiazygos vein in patients with progressive cyanosis
      after performing the bidirectional Glenn procedure. METHODS: From January 2007 to
      May 2011, transcatheter closure was performed on 9 patients (7 males and 2
      females) aged 5-15 years (median 9 years). RESULTS: A total of 7 azygos veins and
      3 hemiazygos veins were occluded successfully. Coils were employed in 4 of the
      procedures, patent ductus arteriosus (PDA) occluders in 3, atrial septal defect
      occluders in 2 and a PDA occluder together with coils in 1 procedure. Immediate
      complete occlusions were achieved in 9 (81.8%) procedures and trivial residual
      shunt in 2 (18.2%). The femoral artery oxygen saturation (SaO2) rose from 81
      [interquartile range (IQR) 75-86%] to 88% (IQR 84-91%). CONCLUSIONS: Patients
      with superior vena cava azygos vein collateral channels can be treated
      successfully by transcatheter occlusion with multiple devices. The device for
      embolization depends on the extent of the severity of the shunt, the size of the
      lumen of the azygos vein/hemiazygos vein and the candidate location for
      occlusion.

PMID- 24903600
TI  - Pericellular proteolysis by matrix metalloproteinase-7 is differentially
      modulated by cholesterol sulfate, sulfatide, and cardiolipin.
AB  - Matrix metalloproteinase (MMP)-7 binds to cell surface cholesterol sulfate (CS)
      and acts as a membrane-associated protease. We have previously found that CS
      modulates the substrate preference of MMP-7, thereby regulating its pericellular
      proteolytic action. MMP-7 potentially associates with the cell surface via
      sulfatide (SM4) and cardiolipin (CL) when they are overexpressed on the cell
      surface. Here, we investigated the molecular interaction between these acidic
      lipids and MMP-7 or its substrates, and their effects on the activity of MMP-7.
      Studies using MMP-7 variants with low CS-binding ability suggested that these
      lipids interact with a similar site on MMP-7. The hydroxamate-based MMP inhibitor
      TAPI-1 markedly reduced the affinity of MMP-7 for CS and CL, whereas that for SM4
      was not affected by TAPI-1. These three acidic lipids also had different effects
      on the hydrolytic activity of MMP-7 towards a small peptide substrate: SM4, CL
      and CS reduced the activity to 80%, 92%, and 20%, respectively. Nevertheless, SM4
      and CS similarly accelerated the MMP-7-catalyzed degradation of fibronectin and
      laminin-332, whereas CL did not. The increased proteolysis of substrate was
      observed only when both substrate and enzyme had affinity for the lipid,
      suggesting that the lipids probably bring the reactants into closer proximity.
      Furthermore, MMP-7 bound to cell surface SM4 or CS cleaved specific cell surface
      proteins and released similar fragments, whereas the cleavage was not stimulated
      by cell surface CL-bound MMP-7. This study provides a novel mechanism by which
      acidic lipids differentially regulate pericellular proteolysis by MMP-7 through
      allosteric alteration of the substrate-binding site and their inherent affinities
      for MMP-7 substrates. 

PMID- 24903601
TI  - Isolation and characterization of a novel bacteriophage against Mycobacterium
      avium subspecies paratuberculosis.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of
      Johne's disease, has a doubling time of 24 hours, making rapid detection very
      difficult. Mycobacteriophages can be used in the detection of disease-causing
      mycobacteria such as MAP. Isolation and sequencing the genomes of lytic MAP
      bacteriophages are important preliminary steps towards designing phage-based
      rapid detection assays for this bacterium. A simple optimized protocol was
      developed to allow reproducible production of confluent growth of MAP on plates
      within four to six weeks of incubation at 30  degrees C. This protocol was
      applied to the screening of environmental and fecal samples for bacteriophages
      inhibiting the growth of MAP. As a result, a lytic phage, vB_MapS_FF47, was
      isolated from bovine feces. FF47 contains a double-stranded DNA genome ~48 kb in
      length with 73 protein coding sequences. It does not carry temperate or known
      virulence genes. This phage was shown to be most closely related to Mycobacterium
      phage Muddy, isolated in South Africa, and Gordonia phage GTE2; however, it could
      not infect any of the tested Gordonia, Rhodococcus, or Nocardia spp. that GTE2
      could. The protocols that were developed for growth and phage isolation have
      potential applications in a high-throughput screening for compounds inhibiting
      the growth of MAP. This work describes the first time that a phage was isolated
      against M. paratuberculosis.

PMID- 24903602
TI  - Genome sequence of a pathogenic isolate of monkey B virus (species Macacine
      herpesvirus 1).
AB  - The only genome sequence for monkey B virus (BV; species Macacine herpesvirus 1)
      is that of an attenuated vaccine strain originally isolated from a rhesus monkey
      (BVrh). Here we report the genome sequence of a virulent BV strain isolated from
      a cynomolgus macaque (BVcy). The overall genome organization is the same,
      although sequence differences exist. The greatest sequence divergence is located
      in non-coding areas of the long and short repeat regions. Like BVrh, BVcy has
      duplicated Ori elements and lacks an ORF corresponding to the gamma34.5 gene of
      herpes simplex virus. Nine of ten miRNAs and the majority of ORFs are conserved
      between BVrh and BVcy. The most divergent genes are several membrane-associated
      proteins and those encoding immediate early proteins.

PMID- 24903603
TI  - Role of water structure on the high pressure micellization and phase
      transformations of sodium dodecanoate aqueous solutions.
AB  - The aim of this work is to study the micelle formation and possible subsequent
      transformations of sodium dodecanoate aggregates in aqueous solutions at
      pressures up to 700 MPa. This pressure range is much larger than in most
      available studies on surfactant solutions and allows for evaluating the possible
      effect of the low-density to high-density water transformation on the aggregative
      behavior of the surfactant. The speed-of-sound and attenuation coefficient were
      determined at 298.15 K as a function of pressure at concentrations up to 0.13 mol
      kg(-1) in water. The speed-of-sound behavior with concentration is maintained up
      to pressures around 350 MPa. The attenuation coefficient, initially insensitive
      to pressure, exhibits a sudden increase around 250 MPa, reaching a maximum around
      350 MPa and a plateau above 500 MPa in the case of the highest studied surfactant
      concentrations. From the analysis of the changes observed in these properties, it
      was possible to extend the concentration-pressure phase diagram of sodium
      dodecanoate at constant temperature. Some peculiarities found were: (1) the
      critical micellar concentration reaches a maximum around 170 MPa, (2) the
      micellar phase disappears above 400 MPa, (3) a phase transformation starts around
      250 MPa, setting the solubility limit of the surfactant at concentrations around
      0.06 mol kg(-1) in this pressure region, and (4) further transformations occur
      between 350 and 500 MPa. We discuss in length the possibility that such
      transformations might be driven by structural changes linked to the so-called low
      density-water to high-density-water transition. 

PMID- 24903604
TI  - Practice-centred evaluation and the privileging of care in health information
      technology evaluation.
AB  - Our contribution, drawn from our experience of the case study provided, is a
      protocol for practice-centred, participative evaluation of technology in the
      clinical setting that privileges care. In this context 'practice-centred'
      evaluation acts as a scalable, coordinating framework for evaluation that
      recognises health information technology supported care as an achievement that is
      contingent and ongoing. We argue that if complex programmes of technology-enabled
      service innovation are understood in terms of their contribution to patient care
      and supported by participative, capability-building evaluation methodologies,
      conditions are created for practitioners and patients to realise the potential of
      technologies and make substantive contributions to the evidence base underpinning
      health innovation programmes. BACKGROUND: Electronic Patient Records (EPRs) and
      telemedicine are positioned by policymakers as health information technologies
      that are integral to achieving improved clinical outcomes and efficiency savings.
      However, evaluating the extent to which these aims are met poses distinct
      evaluation challenges, particularly where clinical and cost outcomes form the
      sole focus of evaluation design. We propose that a practice-centred approach to
      evaluation - in which those whose day-to-day care practice is altered (or not) by
      the introduction of new technologies are placed at the centre of evaluation
      efforts - can complement and in some instances offer advantages over, outcome
      centric evaluation models. METHODS: We carried out a regional programme of
      innovation in renal services where a participative approach was taken to the
      introduction of new technologies, including: a regional EPR system and a system
      to support video clinics. An 'action learning' approach was taken to procurement,
      pre-implementation planning, implementation, ongoing development and evaluation.
      Participants included clinicians, technology specialists, patients and external
      academic researchers. Whilst undergoing these activities we asked: how can a
      practice-centred approach be embedded into evaluation of health information
      technologies? DISCUSSION: Organising EPR and telemedicine evaluation around
      predetermined outcome measures alone can be impractical given the complex and
      contingent nature of such projects. It also limits the extent to which unforeseen
      outcomes and new capabilities are recognised. Such evaluations often fail to
      improve understanding of 'when' and 'under what conditions' technology-enabled
      service improvements are realised, and crucially, how such innovation improves
      care. SUMMARY: Our contribution, drawn from our experience of the case study
      provided, is a protocol for practice-centred, participative evaluation of
      technology in the clinical setting that privileges care. In this context
      'practice-centred' evaluation acts as a scalable, coordinating framework for
      evaluation that recognises health information technology supported care as an
      achievement that is contingent and ongoing. We argue that if complex programmes
      of technology-enabled service innovation are understood in terms of their
      contribution to patient care and supported by participative, capability-building
      evaluation methodologies, conditions are created for practitioners and patients
      to realise the potential of technologies and make substantive contributions to
      the evidence base underpinning health innovation programmes.

PMID- 24903605
TI  - Executive functioning and speech-language skills following long-term use of
      cochlear implants.
AB  - Neurocognitive processes such as executive functioning (EF) may influence the
      development of speech-language skills in deaf children after cochlear
      implantation in ways that differ from normal-hearing, typically developing
      children. Conversely, spoken language abilities and experiences may also exert
      reciprocal effects on the development of EF. The purpose of this study was to
      identify EF domains that are related to speech-language skills in cochlear
      implant (CI) users, compared to normal-hearing peers. Sixty-four prelingually
      deaf, early-implanted, long-term users of CIs and 74 normal-hearing peers
      equivalent in age and nonverbal intelligence completed measures of speech
      language skills and three domains of EF: working memory, fluency-speed, and
      inhibition-concentration. Verbal working memory and fluency-speed were more
      strongly associated with speech-language outcomes in the CI users than in the
      normal-hearing peers. Spatial working memory and inhibition-concentration
      correlated positively with language skills in normal-hearing peers but not in CI
      users. The core domains of EF that are associated with spoken language
      development are different in long-term CI users compared to normal-hearing peers,
      suggesting important dissociations in neurocognitive development. 

PMID- 24903606
TI  - Automatic segmentation of the aortic root in CT angiography of candidate patients
      for transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation is a minimal-invasive intervention for
      implanting prosthetic valves in patients with aortic stenosis. Accurate automated
      sizing for planning and patient selection is expected to reduce adverse effects
      such as paravalvular leakage and stroke. Segmentation of the aortic root in CTA
      is pivotal to enable automated sizing and planning. We present a fully automated
      segmentation algorithm to extract the aortic root from CTA volumes consisting of
      a number of steps: first, the volume of interest is automatically detected, and
      the centerline through the ascending aorta and aortic root centerline are
      determined. Subsequently, high intensities due to calcifications are masked.
      Next, the aortic root is represented in cylindrical coordinates. Finally, the
      aortic root is segmented using 3D normalized cuts. The method was validated
      against manual delineations by calculating Dice coefficients and average distance
      error in 20 patients. The method successfully segmented the aortic root in all 20
      cases. The mean Dice coefficient was 0.95 +/- 0.03, and the mean radial absolute
      error was 0.74 +/- 0.39 mm, where the interobserver Dice coefficient was 0.95 +/-
      0.03 and the mean error was 0.68 +/- 0.34 mm. The proposed algorithm showed
      accurate results compared to manual segmentations.

PMID- 24903608
TI  - Predicting new Ugi-smiles couplings: a combined experimental and theoretical
      study.
AB  - Following our previous mechanistic studies of multicomponent Ugi-type reactions,
      theoretical calculations have been performed to predict the efficiency of new
      substrates in Ugi-Smiles couplings. First, as predicted, 2,4,6-trichlorophenol
      experimentally gave the corresponding aryl-imidate. Theoretical predictions of
      nitrosophenols as good acidic partners were then successfully confirmed by
      experiments. In the latter case, the reaction offers a new access to
      benzimidazoles. 

PMID- 24903607
TI  - Identification, cloning and characterization of the tomato TCP transcription
      factor family.
AB  - BACKGROUND: TCP proteins are plant-specific transcription factors, which are
      known to have a wide range of functions in different plant species such as in
      leaf development, flower symmetry, shoot branching, and senescence. Only a small
      number of TCP genes has been characterised from tomato (Solanum lycopersicum).
      Here we report several functional features of the members of the entire family
      present in the tomato genome. RESULTS: We have identified 30 Solanum lycopersicum
      SlTCP genes, most of which have not been described before. Phylogenetic analysis
      clearly distinguishes two homology classes of the SlTCP transcription factor
      family - class I and class II. Class II differentiates in two subclasses, the CIN
      TCP subclass and the CYC/TB1 subclass, involved in leaf development and axillary
      shoots formation, respectively. The expression patterns of all members were
      determined by quantitative PCR. Several SlTCP genes, like SlTCP12, SlTCP15 and
      SlTCP18 are preferentially expressed in the tomato fruit, suggesting a role
      during fruit development or ripening. These genes are regulated by RIN (RIPENING
      INHIBITOR), CNR (COLORLESS NON-RIPENING) and SlAP2a (APETALA2a) proteins, which
      are transcription factors with key roles in ripening. With a yeast one-hybrid
      assay we demonstrated that RIN binds the promoter fragments of SlTCP12, SlTCP15
      and SlTCP18, and that CNR binds the SlTCP18 promoter. This data strongly suggests
      that these class I SlTCP proteins are involved in ripening. Furthermore, we
      demonstrate that SlTCPs bind the promoter fragments of members of their own
      family, indicating that they regulate each other. Additional yeast one-hybrid
      studies performed with Arabidopsis transcription factors revealed binding of the
      promoter fragments by proteins involved in the ethylene signal transduction
      pathway, contributing to the idea that these SlTCP genes are involved in the
      ripening process. Yeast two-hybrid data shows that SlTCP proteins can form homo
      and heterodimers, suggesting that they act together in order to form functional
      protein complexes and together regulate developmental processes in tomato.
      CONCLUSIONS: The comprehensive analysis we performed, like phylogenetic analysis,
      expression studies, identification of the upstream regulators and the
      dimerization specificity of the tomato TCP transcription factor family provides
      the basis for functional studies to reveal the role of this family in tomato
      development.

PMID- 24903609
TI  - Using standardized patients to train telephone counselors for a clinical trial.
AB  - BACKGROUND: Standardized Patients (SPs) are actors trained to portray health care
      patients during the training and assessment of health care providers. This paper
      describes the methods and costs associated with using SPs to evaluate the skills
      of telephone counselors working on a clinical trial that evaluated a telephone
      smoking cessation program tailored for smokers using Department of Veterans
      Affairs mental health clinics. FINDINGS: Conducting the SP exercises required
      five main steps: (1) Write a SP case description detailing patient demographics,
      demeanor, clinical symptoms and history, and instructions on how to respond to
      counseling, (2) Identify, select and train actors to portray the SP cases; (3)
      Conduct audio-taped counseling encounters between the SPs and counselors, (4)
      Rate the counselors on their core counseling competencies, (5) Provide feedback
      to counselors. The SPs and study supervisors reported that the checklist was easy
      to use when rating the counselors. Counselors reported that the SP encounters
      were realistic and helpful for practicing their clinical work and for building
      self-efficacy for working with real patients. The labor costs of developing two
      SP cases and training two SP actors was approximately $1,475. The per-session
      labor cost of conducting a 1-hour counseling session between one SP and one
      counselor was approximately $314. CONCLUSIONS: Using SPs to train telephone
      counselors working on a clinical trial was feasible and offered training benefits
      beyond those provided by didactic instruction and role plays. Our research group
      is now routinely using SPs for the training of incoming telephone counselors.

PMID- 24903610
TI  - Modeling the active site of [NiFe] hydrogenases and the [NiFeu] subsite of the C
      cluster of carbon monoxide dehydrogenases: low-spin iron(II) versus high-spin
      iron(II).
AB  - A series of four [S2Ni(MU-S)2FeCp*Cl] compounds with different tetradentate
      thiolate/thioether ligands bound to the Ni(II) ion is reported (Cp* = C5Me5). The
      {S2Ni(MU-S)2Fe} core of these compounds resembles structural features of the
      active site of [NiFe] hydrogenases. Detailed analyses of the electronic
      structures of these compounds by Mossbauer and electron paramagnetic resonance
      spectroscopy, magnetic measurements, and density functional theory calculations
      reveal the oxidation states Ni(II) low spin and Fe(II) high spin for the metal
      ions. The same electronic configurations have been suggested for the Cred1 state
      of the C-cluster [NiFeu] subsite in carbon monoxide dehydrogenases (CODH). The Ni
      Fe distance of ~3 A excludes a metal-metal bond between nickel and iron, which is
      in agreement with the computational results. Electrochemical experiments show
      that iron is the redox active site in these complexes, performing a reversible
      one-electron oxidation. The four complexes are discussed with regard to their
      similarities and differences both to the [NiFe] hydrogenases and the C-cluster of
      Ni-containing CODH. 

PMID- 24903611
TI  - Glucose gradients influence zonal matrix deposition in 3D cartilage constructs.
AB  - Reproducing the native collagen structure and glycosaminoglycan (GAG)
      distribution in tissue-engineered cartilage constructs is still a challenge.
      Articular cartilage has a specific nutrient supply and mechanical environment due
      to its location and function in the body. Efforts to simulate this native
      environment have been reported through the use of bioreactor systems. However,
      few of these devices take into account the existence of gradients over cartilage
      as a consequence of the nutrient supply by diffusion. We hypothesized that
      culturing chondrocytes in an environment, in which gradients of nutrients can be
      mimicked, would induce zonal differentiation. Indeed, we show that glucose
      gradients facilitating a concentration distribution as low as physiological
      glucose levels enhanced a zonal chondrogenic capacity similar to the one found in
      native cartilage. Furthermore, we found that the glucose consumption rates of
      cultured chondrocytes were higher under physiological glucose concentrations and
      that GAG production rates were highest in 5 mM glucose. From these findings, we
      concluded that this condition is better suited for matrix deposition compared to
      20 mM glucose standard used in a chondrocyte culture system. Reconsidering the
      culture conditions in cartilage tissue engineering strategies can lead to
      cartilaginous constructs that have better mechanical and structural properties,
      thus holding the potential of further enhancing integration with the host tissue.

PMID- 24903612
TI  - Home environmental determinants of children's fruit and vegetable consumption
      across different SES backgrounds.
AB  - OBJECTIVE: To investigate the association between home environmental determinants
      of fruit and vegetable consumption with childhood overweight separately for low,
      medium and high social economic status (SES) families. METHOD: A cross-sectional
      study was carried out in 2006 among 4072 children aged 4-13 years in the city of
      Zwolle, the Netherlands. Of these children, data were available on measured
      height and weight, and from a parental questionnaire, on sociodemographic
      characteristics and children's fruit and vegetables intake. Associations were
      studied using logistic regression analyses. RESULTS: Not eating the recommended
      amounts of vegetables daily was associated with overweight for children with a
      low SES background (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.66
      2.07) and medium SES background (OR: 1.73; 95% CI: 1.20-2.49). Eating < 2 pieces
      of fruit daily was associated with a lower OR for overweight among children with
      a high SES background (OR: 0.66; 95% CI: 0.50-0.88). Determinants of eating
      vegetables < 7 d were: permission to take candy without asking, eating at the
      table < 7 d per week, eating a takeaway meal >= 1 d per week, eating a home
      cooked meal < 6 d per week and cooking together with caregiver less than 5 d per
      week. CONCLUSION: Interventions regarding vegetable consumption should be
      tailored to families with low and medium SES background. The most promising
      avenues for intervention seem to be (i) to prevent eating takeaway meals on a
      weekly basis and, (ii) to promote eating a home cooked meal at the table and
      (iii) to involve children in the cooking process. Interventions should support
      parents in making these home environmental changes.

PMID- 24903614
TI  - Expression of cytokines, chemokines and other effector molecules in two
      prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet's
      syndrome.
AB  - Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) are two inflammatory skin
      diseases presenting with painful ulcers and erythematous plaques, respectively;
      both disorders have a debilitating clinical behaviour and PG is potentially life
      threatening. Recently, PG and SS have been included among the autoinflammatory
      diseases, which are characterized by recurrent episodes of sterile inflammation,
      without circulating autoantibodies and autoreactive T cells. However, an
      autoinflammatory pattern clearly supporting this inclusion has never been
      demonstrated. We studied 16 patients with PG, six with SS and six controls,
      evaluating, using a sandwich-based protein antibody array method, the expression
      profile of inflammatory effector molecules in PG, SS and normal skin. The
      expressions of interleukin (IL)-1 beta and its receptor I were significantly
      higher in PG (P = 0.0001 for both) and SS (P = 0.004-0.040) than in controls. In
      PG, chemokines such as IL-8 (P = 0.0001), chemokine (C-X-C motif) ligand (CXCL)
      1/2/3 (P = 0.002), CXCL 16 (P = 0.003) and regulated upon activation normal T
      cell expressed and secreted (RANTES) (P = 0.005) were over-expressed. In SS, IL-8
      (P = 0.018), CXCL 1/2/3 (P = 0.006) and CXCL 16 (P = 0.036) but not RANTES were
      over-expressed, suggesting that chemokine-mediated signals are lower than in PG.
      Fas/Fas ligand and CD40/CD40 ligand systems were over-expressed in PG (P = 0.0001
      for Fas, P = 0.009 for Fas ligand, P = 0.012 for CD40, P = 0.0001 for CD40
      ligand), contributing to tissue damage and inflammation, while their role seems
      to be less significant in SS. Over-expression of cytokines/chemokines and
      molecules amplifying the inflammatory network supports the view that PG and SS
      are autoinflammatory diseases. The differences in expression profile of
      inflammatory effectors between these two disorders may explain the stronger local
      aggressiveness in PG than SS.

PMID- 24903615
TI  - Crosstalk between circadian rhythmicity, mitochondrial dynamics and macrophage
      bactericidal activity.
AB  - Biological functions show rhythmic fluctuations with 24-hr periodicity regulated
      by circadian proteins encoded by the so-called 'clock' genes. The absence or
      deregulation of circadian proteins in mice leads to metabolic disorders and in
      vitro models have shown that the synthesis of pro-inflammatory cytokines by
      macrophages follows a circadian rhythm so showing a link between circadian
      rhythmicity, metabolism and immunity. Recent evidence reveals that mitochondrial
      shape, position and size, collectively referred to as mitochondrial dynamics, are
      related to both cell metabolism and immune function. However, studies addressing
      the simultaneous crosstalk between circadian rhythm, mitochondrial dynamics and
      cell immune function are scarce. Here, by using an in vitro model of synchronized
      murine peritoneal macrophages, we present evidence that the mitochondrial
      dynamics and the mitochondrial membrane potential (?psim ) follow a circadian
      rhythmic pattern. In addition, it is shown that the fusion of mitochondria along
      with high ?psim , indicative of high mitochondrial activity, precede the highest
      phagocytic and bactericidal activity of macrophages on Salmonella typhimurium.
      Taken together, our results suggest a timely coordination between circadian
      rhythmicity, mitochondrial dynamics, and the bactericidal capacity of
      macrophages. 

PMID- 24903616
TI  - Motor progression of Parkinson's disease with the leucine-rich repeat kinase 2
      G2019S mutation.
AB  - INTRODUCTION: In this retrospective study, we compared motor disease progression
      in Ashkenazi-Jewish (AJ) Parkinson's disease (PD) patients carrying the
      LRRK2*G2019S mutation with that of noncarriers. METHODS: Consecutive PD patients
      were recruited between 2004 and 2011. Disease progression of carriers versus
      noncarriers was compared using survival analysis, where the end-point was the
      time from PD onset to reaching Hoehn and Yahr stage 3 (HY3). RESULTS: Overall,
      405 AJ PD patients (males = 241[60%]) were genotyped, of whom 60 (males = 30)
      were LRRK2*G2019S mutation carriers. Time to HY3 did not differ significantly
      between mutation carriers and noncarriers (hazard ratio = 1.21, 95%CI = 0.83
      1.77, P = 0.33). Age at PD onset was younger for carriers than for noncarriers
      (59.1 +/- 9.8 vs. 63.2 +/- 12.0 years, respectively; P = 0.005). In both groups,
      young age at onset was strongly associated with longer time to HY3, (P < 0.001).
      CONCLUSION: The LRRK2*G2019S mutation status has no discernible effect on the
      rate of motor disease progression in AJ PD patients.

PMID- 24903617
TI  - Design, synthesis, and pharmacological evaluation of novel 2-(4-substituted
      piperazin-1-yl)1, 8 naphthyridine 3-carboxylic acids as 5-HT3 receptor
      antagonists for the management of depression.
AB  - 1, 8-naphthyridine-3-carboxylic acid analogs were synthesized and found to
      possess potential 5-HT3 receptor antagonism as well as antidepressant-like
      activity. Initially, 5-HT3 receptor antagonism of all the compounds was
      determined in the form of pA2 value against agonist 2-methyl 5-HT in longitudinal
      muscle-myenteric plexus preparation from guinea-pig ileum. Among all the
      compounds tested, compound 7a demonstrated most promising pA2 value of 7.6.
      Subsequently, all the compounds were evaluated for antidepressant activity using
      forced swim test and tail suspension test in mice. Compounds 7a, 7d, 7f, 7h, and
      7i exhibited significant (p < 0.05) antidepressant-like activity as compound to
      vehicle-treated group. Importantly, none of the tested compound affected
      locomotor activity of mice at tested dose levels. 

PMID- 24903618
TI  - Repeated biopsies in patients with prostate cancer on active surveillance:
      clinical implications of interobserver variation in histopathological assessment.
AB  - OBJECTIVE: To investigate the clinical implications of interobserver variation in
      the assessment of re-biopsies obtained during active surveillance (AS) of
      prostate cancer. PATIENTS AND METHODS: In all, 107 patients with low-risk
      prostate cancer with 93 diagnostic biopsy sets and 109 re-biopsy sets were
      included. The International Society of Urological Pathology 2005 Gleason scoring
      system was used for the histopathological assessment of all biopsies. Three
      different definitions of histopathological progression were applied. Unweighted
      and linear weighted Kappa (kappa) statistics were used to compare the
      interobserver agreement. RESULTS: The overall Gleason score agreement was 68.8%
      with a weighted kappa of 0.670. The interobserver agreement was 79.6% for meeting
      the AS selection criteria. According to the three progression definitions
      applied, overall agreement was between 80.7% and 89.0% with weighted kappa values
      of 0.746-0.791. Treatment recommendations would have changed in up to 10.1% (95%
      confidence interval 5.4-17.7%) of the 109 re-biopsy sets. CONCLUSION: Kappa
      statistics showed strong agreement between the histological evaluations. However,
      up to 10% of patients on AS would receive a different treatment recommendation
      depending upon which histopathological evaluation of re-biopsies was used for
      treatment planning.

PMID- 24903619
TI  - Study of the frequency of Clostridium difficile tcdA, tcdB, cdtA and cdtB genes
      in feces of Calves in south west of Iran.
AB  - BACKGROUND: Clostridium difficile (C. difficile) is a gram-positive, toxin
      producing bacillus which is an intestinal pathogen in both humans and animals and
      causes a range of digestive disorders including inflammation of the bowel,
      abdominal pain, fever and diarrhea. C. difficile toxins include enterotoxin
      (Toxin A), cytotoxin (Toxin B) and a binary toxin. Two large protein toxins A and
      B are encoded by separate genes, tcdA and tcdB. Clostridium difficile infection
      (CDI) mainly caused by the activity of the genes tcdA and tcdB. The binary toxin
      is encoded by the genes cdtA and cdtB. The binary toxin caused increased
      adherence of bacteria to intestinal epithelium. The aim of the present study was
      isolation of C. difficile from feces of calves, and study of the frequency of C.
      difficile virulence genes. METHODS: 150 samples of fresh feces from calves were
      collected and C. difficile was isolated from feces of calves using bacterial
      culture methods. DNA was extracted by a genomic DNA purification kit. Then PCR
      method was used for definitive diagnosis of C. difficile. Multiplex PCR method
      performed for identification of tcdA, tcdB, cdtA and cdtB genes. In the final
      stage antimicrobial resistance determining was carried out by standard Bauer
      Kirby disk diffusion method. RESULTS: C. difficile was isolated from 90 samples
      (60%). The tcdA was observed in 8 isolates (8.8%), tcdB in 16 isolates (17.7%),
      cdtA in 8 isolates (8.8%) and cdtB in 14 isolates (15.5%). Only 1 isolated (1.1%)
      was containing all four genes tcdA, tcdB, cdtA and cdtB, 2 isolates (2.2%) only
      had both tcdA and tcdB genes, and there was no sample positive only for both cdtA
      and cdtB. The highest rate of drug resistance was against clindamycin (100%) and
      the highest rate of drug sensitivity was against ciprofloxacin (50%). CONCLUSION:
      The results showed high incidence of C. difficile and also high antibiotic
      resistance of this bacterium, but frequency of strains containing virulence genes
      (tcdA, tcdB, cdtA and cdtB) was low.

PMID- 24903620
TI  - A theory-based online health behaviour intervention for new university students
      (U@Uni): results from a randomised controlled trial.
AB  - BACKGROUND: Too few young people engage in behaviours that reduce the risk of
      morbidity and premature mortality, such as eating healthily, being physically
      active, drinking sensibly and not smoking. This study sought to assess the
      efficacy and cost-effectiveness of a theory-based online health behaviour
      intervention (based on self-affirmation theory, the Theory of Planned Behaviour
      and implementation intentions) targeting these behaviours in new university
      students, in comparison to a measurement-only control. METHODS: Two-weeks before
      starting university all incoming undergraduates at the University of Sheffield
      were invited to take part in a study of new students' health behaviour. A
      randomised controlled design, with a baseline questionnaire, and two follow-ups
      (1 and 6 months after starting university), was used to evaluate the
      intervention. Primary outcomes were measures of the four health behaviours
      targeted by the intervention at 6-month follow-up, i.e., portions of fruit and
      vegetables, metabolic equivalent of tasks (physical activity), units of alcohol,
      and smoking status. RESULTS: The study recruited 1,445 students (intervention n =
      736, control n = 709, 58% female, Mean age = 18.9 years), of whom 1,107 completed
      at least one follow-up (23% attrition). The intervention had a statistically
      significant effect on one primary outcome, smoking status at 6-month follow-up,
      with fewer smokers in the intervention arm (8.7%) than in the control arm (13.0%;
      Odds ratio = 1.92, p = .010). There were no significant intervention effects on
      the other primary outcomes (physical activity, alcohol or fruit and vegetable
      consumption) at 6-month follow-up. CONCLUSIONS: The results of the RCT indicate
      that the online health behaviour intervention reduced smoking rates, but it had
      little effect on fruit and vegetable intake, physical activity or alcohol
      consumption, during the first six months at university. However, engagement with
      the intervention was low. Further research is needed before strong conclusions
      can be made regarding the likely effectiveness of the intervention to promote
      health lifestyle habits in new university students. TRIAL REGISTRATION: Current
      Controlled Trials, ISRCTN67684181.

PMID- 24903622
TI  - Brugada phenocopy in concomitant ethanol and heroin overdose.
AB  - Brugada phenocopy describes conditions with Brugada-like ECG pattern but without
      true congenital Brugada syndrome. We report a case of 44-year-old man with no
      known medical history who presented with loss of consciousness. Toxicology
      screening was positive for opiates and high serum alcohol level. His initial ECG
      showed Brugada type 1 pattern which resolved after several hours of observation
      and treatment with continuous naloxone infusion. Patient regained his
      consciousness and disclosed heroin abuse and drinking alcohol. This case
      highlights the heroin overdose as a possible cause of Brugada phenocopy. 

PMID- 24903621
TI  - Current prevention strategies against cytomegalovirus in the studies in pediatric
      liver transplantation (SPLIT) centers.
AB  - Cytomegalovirus (CMV) continues to be a significant posttransplant infectious
      complication after pediatric liver transplant (PLT). The optimal prevention
      strategy is not currently known. To assess current CMV prevention practices, a
      web-based survey was conducted within the North American Studies in Pediatric
      Liver Transplantation (SPLIT) network. Twenty-nine of the 31 centers (94%)
      surveyed responded. Only seven centers reported evidence-based development of
      protocols. For most at-risk (donor or recipient CMV seropositive) PLT recipients,
      a prophylactic strategy predominates current practice. For high-risk (D+/R-),
      only three centers used nonprophylaxis-based protocols: one preemptive and two
      sequential/hybrid. Duration of prophylaxis ranged from 84 to 730 days with 14
      centers using around 100 days and nine centers using around 200 days. Initial
      therapy with ganciclovir followed by valganciclovir was the most common strategy.
      For lower-risk recipients (CMV D-/R-), more centers (10/29) employed a preemptive
      strategy while the remainder described prophylaxis (15) and sequential/hybrid (3)
      strategies. Prophylaxis predominates current CMV prevention strategies for at
      risk recipients within SPLIT. The variation in duration of therapy provides the
      opportunity to perform comparative effectiveness studies within SPLIT. 

PMID- 24903623
TI  - Improving the coaching and mentoring of IMGs.

PMID- 24903626
TI  - Platelets in asthma: does size matter?

PMID- 24903624
TI  - Association between macroorchidism and intelligence in FMR1 premutation carriers.
AB  - Characteristics of fragile X syndrome include macroorchidism and intellectual
      disability, which are associated with decreased FMRP levels. FMRP is highly
      expressed in many tissues, but primarily in the brain and testis. The
      relationship between these two characteristics has not previously been studied in
      the premutation or carrier state. To examine this among premutation carriers and
      a possible association with IQ, we evaluated macroorchidism status among 213
      males including 142 premutation carriers and 71 controls. The prevalence of
      macroorchidism among premutation carriers was 32.4% (46 out of 142), and 5.6%
      among controls (4 out of 71, P < 0.0001). Among premutation carriers, the age
      adjusted odds ratio (OR) of macroorchidism was significantly increased with
      increasing FMR1 mRNA (OR 1.84, 95% confidence interval [CI] 1.04-3.25; P =
      0.035). With respect to the association between macroorchidism and IQ, after
      adjustment for number of CGG repeats and age, premutation carriers with
      macroorchidism had lower verbal IQ (104.67 +/- 15.86, P = 0.0152) and full scale
      IQ (102.98 +/- 15.78, P = 0.0227) than premutation carriers without
      macroorchidism (verbal IQ 112.38 +/- 14.14, full scale IQ 110.24 +/- 14.21).
      Similar associations were observed for both verbal IQ (P = 0.034) and full scale
      IQ (P = 0.039) after being adjusted for age and FMR1 mRNA. These preliminary data
      support a correlation between macroorchidism and lower verbal and full scale IQ
      in a relevant proportion of premutation carrier males. Whether this is due to
      higher levels of FMR1 mRNA or to lower FMRP levels it remains to be established.

PMID- 24903625
TI  - Canine pancreatic-specific lipase concentrations in clinically healthy dogs and
      dogs with naturally occurring hyperadrenocorticism.
AB  - BACKGROUND: Specificity of canine pancreatic lipase immunoreactivity (cPLI)
      assays in dogs with hyperadrenocorticism (HAC) is unknown. HYPOTHESIS: Results of
      cPLI assays differ for clinically healthy dogs and dogs with HAC. ANIMALS:
      Seventeen healthy dogs and 20 dogs with HAC diagnosed by ACTH stimulation test
      results without evidence of clinical pancreatitis. METHODS: Dogs were enrolled
      between December 2009 and November 2010. Serum cPLI concentrations were
      determined by quantitative (Spec cPL test, SPEC) and semiquantitative (SNAP cPL
      test, SNAP) assays. Results were categorized as normal, equivocal, or abnormal
      (SPEC) or negative or positive (SNAP). Associations between group and cPLI were
      assessed using Fisher's exact test or the Mann-Whitney U-test. Spearman rank
      correlation coefficients (rho) were determined for SNAP and SPEC results.
      Significance was set at P < .05. RESULTS: Spec cPL test concentrations were
      significantly (P < .001) higher in dogs with HAC (491.1 MUg/L) than in healthy
      dogs (75.2 MUg/L), with more abnormal SPEC results in HAC dogs (P < .001). There
      were more (P = .002) positive SNAP results in dogs with HAC (55%) than in healthy
      dogs (6%). SNAP and SPEC results were highly correlated (rho = 0.85; P < .001).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with HAC had higher SPEC concentrations
      and more positive SNAP results than clinically healthy dogs with normal ACTH
      stimulation test results. Specificity of SPEC and SNAP assays in HAC dogs without
      clinical pancreatitis were 65 and 45%, respectively. Pending further study, SNAP
      and SPEC results should be interpreted cautiously in dogs with HAC to avoid false
      diagnosis of concurrent pancreatitis.

PMID- 24903627
TI  - No differences in ventral striatum responsivity between adolescents with a
      positive family history of alcoholism and controls.
AB  - Individuals with alcohol-dependent parents show an elevated risk of developing
      alcohol-related problems themselves. Modulations of the mesolimbic reward circuit
      have been postulated as a pre-existing marker of alcoholism. We tested whether a
      positive family history of alcoholism is correlated with ventral striatum
      functionality during a reward task. All participants performed a modified version
      of the monetary incentive delay task while their brain responses were measured
      with functional magnetic resonance imaging. We compared 206 healthy adolescents
      (aged 13-15) who had any first- or second-degree relative with alcoholism to 206
      matched controls with no biological relative with alcoholism. Reward anticipation
      as well as feedback of win recruited the ventral striatum in all participants,
      but adolescents with a positive family history of alcoholism did not differ from
      their matched peers. Also we did not find any correlation between family history
      density and reward anticipation or feedback of win. This finding of no
      differences did not change when we analyzed a subsample of 77 adolescents with at
      least one parent with alcohol use disorder and their matched controls. Because
      this result is in line with another study reporting no differences between
      children with alcohol-dependent parents and controls at young age, but contrasts
      with studies of older individuals, one might conclude that at younger age the
      effect of family history has not yet exerted its influence on the still
      developing mesolimbic reward circuit. 

PMID- 24903628
TI  - Cell sorting enables interphase fluorescence in situ hybridization detection of
      low BCR-ABL1 producing stem cells in chronic myeloid leukaemia patients beyond
      deep molecular remission.
AB  - The exact disease state of chronic myeloid leukaemia (CML) patients in deep
      molecular remission is unknown, because even the most sensitive quantitative
      reverse transcription polymerase chain reaction (qPCR) methods cannot identify
      patients prone to relapse after treatment withdrawal. To elucidate this, CD34(+)
      stem cell and progenitor cell subpopulations were isolated by fluorescence
      activated cell sorting (FACS), and their content of residual Philadelphia
      positive (Ph(+) ) cells was evaluated in 17 CML patients (major molecular
      response, n = 6; 4-log reduction in BCR-ABL1 expression (MR(4) ), n = 11) using
      both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH).
      Despite evaluating fewer cells, iFISH proved superior to mRNA-based qPCR in
      detecting residual Ph(+) stem cells (P = 0.005), and detected Ph(+) stem- and
      progenitor cells in 9/10 patients at frequencies of 2-14%. Moreover, while all
      qPCR(+) samples also were iFISH(+) , 9/33 samples were qPCR-/iFISH(+) , including
      all positive samples from MR(4) patients. Our findings show that residual Ph(+)
      cells are low BCR-ABL1 producers, and that DNA-based methods are required to
      assess the content of persisting Ph(+) stem cells in these patients. This
      approach demonstrates a clinically applicable manner of assessing residual
      disease at the stem cell level in CML patients in MR(4) , and may enable early
      and safe identification of candidates for tyrosine kinase inhibitor withdrawal. 

PMID- 24903629
TI  - Open-label study of oral CEP-701 (lestaurtinib) in patients with polycythaemia
      vera or essential thrombocythaemia with JAK2-V617F mutation.
AB  - JAK2-V617F is central to the pathogenesis of myeloproliferative neoplasms. We
      examined whether lestaurtinib decreased JAK2-V617F allele burden and evaluated
      its clinical benefits and tolerability in patients with polycythaemia vera (PV)
      and essential thrombocythaemia (ET). This phase 2, open-label, multicentre study
      was designed to detect >=15% reduction in JAK2-V617F allele burden in 15% of
      patients. Eligible patients received lestaurtinib 80 mg twice daily for 18 weeks
      and could participate in a 1-year extension phase of treatment. Of 39 enrolled
      patients, 27 (69%) had PV; 12 (31%) had ET. While the pre-specified responder
      rate of 15% was not met, lestaurtinib modestly reduced JAK2-V617F allele burden
      and reduced spleen size in a subset of patients. Of 37 patients in the full
      efficacy analysis, 5 (14%) responded clinically. Every patient had >=1 adverse
      event, most commonly gastrointestinal (95%). Fifteen patients (38%) experienced
      serious adverse events; 23 (59%) withdrew due to adverse events. This is the
      first reported study of JAK2-inhibitor treatment in patients with PV/ET and
      highlights both the need for further studies to assess the role of JAK2
      inhibition in treatment of PV/ET and the use of JAK2-V617F as a biomarker for
      response. This trial was registered at www.clinicaltrials.gov as NCT00586651.

PMID- 24903630
TI  - Moderate endurance exercise in patients with sickle cell anaemia: effects on
      oxidative stress and endothelial activation.
AB  - Very few studies have investigated the effects of exercise on the biological
      parameters involved in vaso-occlusive events in sickle cell anaemia (SCA). The
      aim of this study was to test how a mild-moderate endurance exercise modulates
      oxidative stress, nitric oxide bioavailability and endothelial activation in SCA
      patients and healthy individuals. Eleven patients with SCA and 15 healthy
      subjects completed a 20-min duration submaximal cycling exercise at ~45 Watts.
      Plasma markers of oxidative stress, antioxidant activity, endothelial activation
      and nitric oxide bioavailability were investigated before and after the exercise.
      Nitric oxide levels, anti-oxidant capacity, soluble (s)E-selectin and sP-selectin
      did not change in response to this exercise. Except for the malondialdehyde
      levels, which increased in the two groups, the other markers of oxidative stress
      remained unchanged in both groups in response to exercise. Soluble vascular cell
      adhesion molecule 1 levels were increased at the end of exercise in both groups.
      sL-selectin decreased and soluble intercellular adhesion molecule 1 increased
      with exercise in SCA patients only. The present data suggest that patients with
      SCA may undertake mild-moderate physical activities without any acute clinical
      complications, but care should be taken because oxidative stress and endothelial
      activation significantly increased in some patients. 

PMID- 24903631
TI  - Revealing the dynamic structure of complex solid catalysts using modulated
      excitation X-ray diffraction.
AB  - X-ray diffraction (XRD) is typically silent towards information on low loadings
      of precious metals on solid catalysts because of their finely dispersed nature.
      When combined with a concentration modulation approach, time-resolved high-energy
      XRD is able to provide the detailed redox dynamics of palladium nanoparticles
      with a diameter of 2 nm in 2 wt % Pd/CZ (CZ = ceria-zirconia), which is a
      difficult sample for extended X-ray absorption fine structure (EXAFS)
      measurements because of the cerium component. The temporal evolution of the
      Pd(111) and Ce(111) reflections together with surface information from
      synchronous diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS)
      measurements reveals that Ce maintains Pd oxidized in the CO pulse, whereas
      reduction is detected at the beginning of the O2 pulse. Oxygen is likely
      transferred from Pd to Ce(3+) before the onset of Pd re-oxidation. In this
      context, adsorbed carbonates appear to be the rate-limiting species for re
      oxidation.

PMID- 24903632
TI  - Characteristics of injury of the corticospinal tract and corticoreticular pathway
      in hemiparetic patients with putaminal hemorrhage.
AB  - BACKGROUND: No study on the characteristics of injury of the corticospinal tract
      (CST) or corticoreticular pathway (CRP) in patients with putaminal hemorrhage has
      been reported. In this study, using diffusion tensor tractography, we attempted
      to investigate the characteristics of injury of the CST and CRP in hemiparetic
      patients with putaminal hemorrhage. METHOD: Fifty seven consecutive patients with
      putaminal hemorrhage and 57 healthy control subjects were recruited for this
      study. Diffusion tensor imaging was performed during the early period (8 ~ 30
      days) after onset. We defined injury of the CST or CRP in terms of the
      configuration (discontinuation of a neural tract) or abnormal DTT parameters (the
      fractional anisotrophy value or fiber number was more than two standard
      deviations lower than that of normal control subjects). The Motricity Index, the
      modified Brunnstrom Classification, and the Functional Ambulation Categories were
      used for evaluation of motor function. RESULTS: Among 57 patients, injury of the
      CST was found in 41 patients (71.9%) and injury of the CRP was found in 50
      patients (87.8%), respectively, and 37 patients (64.9%) had injury of both the
      CST and CRP. All three motor functions of patients with injury of both the CST
      and CRP were significantly lower than those of patients with injury of either the
      CST or CRP (p < 0.05). CONCLUSION: Our results indicate that the putaminal
      hemorrhage frequently accompanies injury of both the CST and CRP, and the CRP
      appears to be more vulnerable to putaminal hemorrhage than the CST. These
      findings suggest the necessity for evaluation of both the CRP and the CST in
      patients with putaminal hemorrhage.

PMID- 24903633
TI  - Distinct functional and structural MRI abnormalities in mesial temporal lobe
      epilepsy with and without hippocampal sclerosis.
AB  - OBJECTIVE: We aimed to investigate patterns of electroencephalography-correlated
      functional MRI (EEG-fMRI) and subtle structural abnormalities in patients with
      mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (MTLE-HS) or
      normal MRI (MTLE-NL). METHODS: We evaluated EEG-fMRI acquisition of the 25
      patients with diagnosis of MTLE who had interictal epileptiform discharges (IEDs)
      in the intra-MRI EEG: 13 MTLE-HS and 12 MTLE-NL. fMRI was performed using echo
      planar images in a 3T MRI coupled with EEG acquired with 64 MRI-compatible
      electrodes. In the first level analyses, the time of the IEDs ipsilateral to the
      epileptogenic zone was used as the paradigm, and four contrasts maps were built
      according to the variation of the hemodynamic response function (HRF) peaks (0,
      +3, +5, and +7 s). Second level group analyses were performed combining the
      contrast maps of MTLE-HS or MTLE-NL patients with each different HRF obtained at
      the first level. Areas of gray matter atrophy were evaluated with voxel-based
      morphometry (VBM) in both groups. RESULTS: MTLE-HS and MTLE-NL had IED-related
      positive BOLD (posBOLD) detected in the ipsilateral anterior temporal lobe and
      insula. However, only MTLE-HS had significant posBOLD on contralateral
      hippocampus and anterior cingulate, whereas MTLE-NL had areas of posBOLD on
      ipsilateral frontal lobe. Both groups had significant IED-related negBOLD
      responses in areas of the default mode network (DMN), such as posterior cingulate
      and precuneus. There was no overlap of both posBOLD and negBOLD and areas of
      atrophy detected by VBM. SIGNIFICANCE: Similar IEDs have different patterns of
      hemodynamic responses in sub-groups of MTLE. In both MTLE-HS and MTLE-NL, there
      is a possible suppression of the DMN related to IEDs, as demonstrated by the
      negBOLD in these areas. The brain areas involved in the interictal related
      hemodynamic network are not the regions with the most significant gray matter
      atrophy in MTLE with or without MRI signs of HS.

PMID- 24903634
TI  - Isolation of Moraxella bovoculi from racehorses with keratoconjunctivitis.
AB  - Moraxella bovoculi was isolated and identified in ocular fluid samples collected
      from 9 racehorses with infectious keratoconjunctivitis in China in 2013. All 9 M.
      bovoculi isolates were hemolytic, Gram-negative diplococci that were
      phenylalanine deaminase positive. The sequence of the 16S ribosomal DNA (rDNA)
      gene of the isolates matched the 16S rDNA sequence of M. bovoculi. Amplification
      of the 16S-23S intergenic spacer region followed by AfaI digestion produced a 600
      base pair product, a result characteristic of M. bovoculi isolates. The
      phylogenetic analysis based on the 16S rDNA sequence confirmed the strain
      isolated in the current study had genetic homology with M. bovoculi.

PMID- 24903635
TI  - A high-throughput biliverdin assay using infrared fluorescence.
AB  - Biliverdin is an intermediate of heme degradation with an established role in
      veterinary clinical diagnostics of liver-related diseases. The need for
      chromatographic assays has so far prevented its wider use in diagnostic
      laboratories. The current report describes a simple, fast, high-throughput, and
      inexpensive assay, based on the interaction of biliverdin with infrared
      fluorescent protein (iRFP) that yields functional protein exhibiting infrared
      fluorescence. The assay is linear in the range of 0-10 umol/l of biliverdin, has
      a limit of detection of 0.02 MUmol/l, and has a limit of quantification of 0.03
      umol/l. The assay is accurate with relative error less than 0.15, and precise,
      with coefficient of variation less than 5% in the concentration range of 2-9
      umol/l of biliverdin. More than 95% of biliverdin was recovered from biological
      samples by simple dimethyl sulfoxide extraction. There was almost no interference
      by hemin, although bilirubin caused an increase in the biliverdin concentration,
      probably due to spontaneous oxidation of bilirubin to biliverdin. The newly
      developed biliverdin assay is appropriate for reliable quantification of large
      numbers of samples in veterinary medicine.

PMID- 24903636
TI  - Inter-word variability of Hungarian affricates /ts, ?/ in the speech of
      monolingual children with and without language disorders.
AB  - This study focuses on the characteristics of inter-word variability (IWV) with
      respect to two Hungarian affricates (/ts, ?/) produced by children with typical
      language development (children with TD) aged 3;0-5;11, and those with primary
      expressive language disorders (children with LD) with the mean age of 6;7. IWV is
      described in terms of frequency of occurrence, the segments realised in place of
      the targets and the error patterns resulting in variable production. Findings
      revealed that variability is characteristic of the production of /?/ in younger
      children with TD, and of both affricates in children with LD. Beside some
      similarities, children with TD and those with LD differed from each other in the
      way in which variable productions emerged. Children with TD committed errors
      typical of their age, and their IWV mostly reflected developmental changes.
      Children with LD, however, demonstrated some indicators of phonological disorders
      such as the persistence of normal simplifications and chronological mismatch.

PMID- 24903637
TI  - Carbapenemase and virulence factors of Enterobacteriaceae in North Lebanon
      between 2008 and 2012: evolution via endemic spread of OXA-48.
AB  - OBJECTIVES: To investigate the resistance to carbapenems in Enterobacteriaceae
      and the underlying resistance mechanisms in North Lebanon between 2008 and 2012.
      METHODS: A total of 2767 Enterobacteriaceae isolates recovered from clinical
      samples collected in Nini Hospital (North Lebanon) were screened for a decrease
      in susceptibility or resistance to ertapenem (MIC >0.25 mg/L). Enterobacteriaceae
      were similarly screened from 183 faecal samples obtained from non-hospitalized
      patients. The bacterial isolates were assigned to clonal lineages by PFGE and
      multilocus sequence typing. Carbapenemase genes, their genetic environment and
      virulence genes were characterized by molecular approaches. RESULTS: The rate of
      Enterobacteriaceae exhibiting a decrease in susceptibility or resistance to
      ertapenem increased from 0.4% in 2008-10 to 1.6% in 2012 for the clinical
      isolates recovered from hospitalized patients. Of these isolates, scattered among
      seven enterobacterial species, 88% produced OXA-48 carbapenemase. However,
      Escherichia coli represented 73% of the OXA-48-producing Enterobacteriaceae
      collected in 2012 at this hospital. During the faecal carriage study performed in
      non-hospitalized patients, E. coli was the only species producing OXA-48. The
      bla(OXA-48) gene was mainly found within Tn1999.2-type transposons inserted into
      E. coli chromosomes or in ~50, ~62 or ~85 kb plasmids. The plasmids and
      chromosomal inserts were related to pOXA-48a. Molecular typing of the isolates
      revealed clonal diversity of E. coli and Klebsiella pneumoniae producing OXA-48.
      OXA-48 was observed in all major E. coli phylogroups, including D and B2, and
      isolates harbouring virulence genes of extra-intestinal pathogenic E. coli.
      Although not belonging to highly virulent capsular genotypes, the OXA-48
      producing K. pneumoniae harboured genes associated with virulence or host
      colonization. CONCLUSIONS: Horizontal transfer of related plasmids has
      facilitated the spread of the bla(OXA-48) gene into several Enterobacteriaceae
      species, including virulent E. coli. Their clonal diversity and the presence of
      faecal carriers in the community suggest an endemic spread of OXA-48.

PMID- 24903638
TI  - Invariant natural killer T cells: boon or bane in immunity to intracellular
      bacterial infections?
AB  - Invariant natural killer T (iNKT) cells represent a specialized subset of innate
      lymphocytes that recognize lipid and glycolipid antigens presented to them by
      nonclassical MHC-I CD1d molecules and are able to rapidly secrete copious amounts
      of a variety of cytokines. iNKT cells possess the ability to modulate innate as
      well as adaptive immune responses against various pathogens. Intracellular
      bacteria are one of the most clinically significant human pathogens that
      effectively evade the immune system and cause a myriad of diseases of public
      health concern globally. Emerging evidence suggests that iNKT cells can confer
      immunity to intracellular bacteria but also inflict pathology in certain cases.
      We summarize the current knowledge on the contribution of iNKT cells in the host
      defense against intracellular bacterial infections, with a focus on the
      underlying mechanisms by which these cells induce protective or pathogenic
      reactions including the pathways of direct action (acting on infected cells) and
      indirect action (modulating dendritic, NK and T cells). The rational exploitation
      of iNKT cells for prophylactic and therapeutic purposes awaits a profound
      understanding of their functional biology.

PMID- 24903639
TI  - Topical application of rapamycin ointment ameliorates Dermatophagoides farina
      body extract-induced atopic dermatitis in NC/Nga mice.
AB  - Atopic dermatitis (AD), a chronic inflammatory skin disease characterized by
      relapsing eczema and intense prurigo, requires effective and safe pharmacological
      therapy. Recently, rapamycin, an mTOR (mammalian target of rapamycin) inhibitor,
      has been reported to play a critical role in immune responses and has emerged as
      an effective immunosuppressive drug. In this study, we assessed whether
      inhibition of mTOR signalling could suppress dermatitis in mice. Rapamycin was
      topically applied to inflamed skin in a murine AD model that was developed by
      repeated topical application of Dermatophagoides farina body (Dfb) extract
      antigen twice weekly for 7 weeks in NC/Nga mice. The efficacy of topical
      rapamycin treatment was evaluated immunologically and serologically. Topical
      application of rapamycin reduced inflammatory cell infiltration in the dermis,
      alleviated the increase of serum IgE levels and resulted in a significant
      reduction in clinical skin condition score and marked improvement of histological
      findings. In addition, increased mTOR phosphorylation in the lesional skin was
      observed in our murine AD model. Topical application of rapamycin ointment
      inhibited Dfb antigen-induced dermatitis in NC/Nga mice, promising a new therapy
      for atopic dermatitis. 

PMID- 24903640
TI  - Evaluation of food provision and nutrition support at the London 2012 Olympic
      Games: the opinion of sports nutrition experts.
AB  - The aim of this study was to evaluate the food provision and nutrition support at
      the London 2012 Olympic (OG) and Paralympic Games (PG) from the perspective of
      sports nutrition experts attending the event. Participants (n = 15) were asked to
      complete an online survey and rate on a Likert scale menu qualities, food safety,
      sustainability practices, nutrition labeling, and provision for cultural needs,
      dietary regimes and specific situations. Open-ended responses were incorporated
      to explore expert opinion and areas for improvement. Participants rated their
      overall experience of the food provision as 7.6 out of 10 (range 5 to 10), with
      the majority (n = 11) rating it greater than 7. The variety, accessibility,
      presentation, temperature, and freshness of menu items rated as average to good.
      A below average rating was received for recovery food and beverages, provision of
      food for traveling to other venues, taking suitable snacks out of the dining hall
      and provision of food at other venues. However, the variety and accessibility of
      choices for Ramadan, and provision of post-competition food were rated highly. A
      number of comments were received about the lack of gluten free and lower
      energy/fat items. The inclusion of allergens on nutrition labeling was considered
      more important than nutrient content. While dietetic review of the menu in
      advance of the OG and PG is clearly a valuable process that has resulted in
      improvements in the food supply, there are still areas that need to be addressed
      that are currently not implemented during the event. 

PMID- 24903641
TI  - Assessing the potential spread and maintenance of foot-and-mouth disease virus
      infection in wild ungulates: general principles and application to a specific
      scenario in Thrace.
AB  - Foot-and-mouth disease (FMD), due to infection with serotype O virus, occurred in
      wild boar and within eleven outbreaks in domestic livestock in the south-east of
      Bulgaria, Thrace region, in 2011. Hence, the issue of the potential for the
      spread and maintenance of FMD virus (FMDV) infection in a population of wild
      ungulates became important. This assessment focused on the spread and maintenance
      of FMDV infection within a hypothetical wild boar and deer population in an
      environment, which is characterized by a climate transitional between
      Mediterranean and continental and variable wildlife population densities. The
      assessment was based on three aspects: (i) a systematic review of the literature
      focusing on experimental infection studies to identify the parameters describing
      the duration of FMDV infection in deer and wild boar, as well as observational
      studies assessing the occurrence of FMDV infection in wild deer and wild boar
      populations, (ii) prevalence survey data of wild boar and deer in Bulgaria and
      Turkey and (iii) an epidemiological model, simulating the host-to-host spread of
      FMDV infections. It is concluded, based on all three aspects, that the wildlife
      population in Thrace, and so wildlife populations in similar ecological settings,
      are probably not able to maintain FMD in the long term in the absence of FMDV
      infection in the domestic host population. However, limited spread of FMDV
      infection in time and space in the wildlife populations can occur. If there is a
      continued cross-over of FMDV between domestic and wildlife populations or a
      higher population density, virus circulation may be prolonged. 

PMID- 24903642
TI  - Pseudotumoral forms of multiple sclerosis: report of 14 cases and review of the
      literature.
AB  - BACKGROUND: The pseudotumoral form of multiple sclerosis (MS) is a rare condition
      with few descriptions in the literature. It supposes a diagnostic challenge
      especially when appearing at the onset of disease. METHODS: We retrospectively
      describe a case series of pseudotumoral MS patients that attended our hospital
      from 2004, analyzing demographic, clinical and radiological variables. We
      classified the lesions according to the recently proposed morphologic
      classification (infiltrative, megacystic, Balo or ring-like) and according to the
      contrast enhancement pattern (nodular, complete ring, incomplete ring and
      diffuse). RESULTS: Fourteen patients (11 female, 3 male), with a mean age of 35
      years, were identified. All of them suffered from a relapsing-remitting form of
      MS. Eleven patients (78.57%) had symptomatic pseudotumoral lesions (PL), being
      the form of clinical presentation in the majority of those patients that were
      symptomatic (81.81%). Several patients presented atypical clinical manifestations
      such as cognitive impairment (21.42%) and epileptic seizures (14.28%). Full
      recovery was found in 53.84% of all symptomatic episodes. After a mean follow-up
      of 43 months, recurrent PL episodes were seldom observed (21.42%), the annualized
      relapse rate was 0.95 and the mean final Expanded Disability Status Scale score
      was 1.5. The majority of PLs were supratentorial, coexisted with typical
      demyelinating plaques and showed the ring-like morphology and the ring pattern of
      contrast enhancement. Three patients had more than one PL on the same scan, all
      of the lesions with similar morphology. CONCLUSIONS: Our findings contribute to a
      better characterization of pseudotumoral forms of MS. However, larger studies are
      required to define this atypical entity more exactly.

PMID- 24903643
TI  - From swill milk to certified milk: progress in cow's milk quality in the 19th
      century.
AB  - BACKGROUND: Industrialization and urbanization jeopardized infant nutrition
      during the 19th century. Cow's milk was produced in the cities or transported
      long distances under suspect conditions. Milk was contaminated with bacteria or
      adulterated with water, flour, chalk and other substances. When distilleries
      proliferated in the metropoles, their waste slop was fed to cows which then
      produced thin and contaminated swill milk. SUMMARY: Following a press campaign in
      the USA, the sale of swill milk was prohibited by law in 1861. Bacterial counts
      became available in 1881 and helped to improve the quality of milk. Debates on
      pasteurization remained controversial; legislation varied from country to
      country. Disposal of the wastewater of millions of inhabitants and the manure of
      thousands of cows was environmentally hazardous. It was not until 1860 and after
      several pandemics of Asiatic cholera that effective sewage systems were built in
      the metropoles. Milk depots were established in the USA by Koplik for sterilized
      and by Coit for certified milk. In France, Budin and Dufour created consultation
      services named goutte de lait, which distributed sterilized milk and educated
      mothers in infant care. MESSAGE: Multiple efforts to improve milk quality
      culminated in the International gouttes de lait Congresses for the Study and
      Prevention of Infantile Mortality.

PMID- 24903644
TI  - Diversity, local knowledge and use of stingless bees (Apidae: Meliponini) in the
      municipality of Nocupetaro, Michoacan, Mexico.
AB  - BACKGROUND: Stingless bees were significant resources managed by Mesoamerican
      peoples during pre-Columbian times and remain important in particular areas. Our
      study aimed at inventorying stingless bees' species, traditional knowledge and
      forms of use and management of them at the municipality of Nocupetaro, Michoacan,
      Mexico, a region of the Balsas River Basin. METHODS: We inventoried the stingless
      bees of the municipality of Nocupetaro, Michoacan, Mexico, through extensive
      collecting of bee specimens in different vegetation types. We then conducted semi
      structured interviews to local experts in order to document their knowledge and
      management techniques of stingless bees' species. RESULTS: We identified a total
      of eight stingless bees' species in the study area as well as three additional
      unidentified taxa recognized by people through the local names. Our inventory
      included one new record of species for the region (Lestrimelitta chamelensis
      Ayala, 1999). The taxa identified are all used by local people. Scaptotrigona
      hellwegeri Friese, 1900; Melipona fasciata Latreille, 1811; Frieseomelitta nigra
      Cresson, 1878 and Geotrigona acapulconis Strand, 1919 are particularly valued as
      food (honey), medicinal (honey and pollen), and material for handcrafts (wax).
      All species recorded are wild and their products are obtained through gathering.
      On average, local experts were able to collect 4 nests of stingless bees per year
      obtaining on average 6 L of honey and 4 Kg of wax but some came to collect up 10
      12 hives per year (18 L of honey and 24 Kg of wax). CONCLUSIONS: Local knowledge
      about use, management and ecological issues on stingless bees is persistent and
      deep in the study area. Information about this group of bees is progressively
      scarcer in Mexico and significant effort should be done from ethnobiological and
      ecological perspectives in order to complement the national inventory of bee
      resources and traditional knowledge and management of them.

PMID- 24903645
TI  - Estimating marbofloxacin withdrawal time in broiler chickens using a population
      physiologically based pharmacokinetics model.
AB  - Residue depletion of marbofloxacin in broiler chicken after oral administration
      at 5 mg/kg/day for three consecutive days was studied in this study. The areas
      under the concentration-time curve from 0 h to infinity (AUC0-infinity s) of
      marbofloxacin in tissues and plasma were used to calculate tissue/plasma
      partition coefficients (PX s). Based on PX s and the other parameters derived
      from published studies, a flow-limited physiologically based pharmacokinetics
      (PBPK) model was developed to predict marbofloxacin concentrations, which were
      then compared with those derived from the residue depletion study so as to
      validate this model. Considering individual difference in drug disposition, a
      Monte Carlo simulation included 1000 iterations was further incorporated into the
      validated model to generate a population PBPK model and to estimate the
      marbofloxacin residue withdrawal times in edible tissues. The withdrawal periods
      were compared to those derived from linear regression analysis. The PBPK model
      presented here successfully predicted the measured concentrations in all tissues.
      The withdrawal times in all edible tissues derived from the population PBPK model
      were longer than those from linear regression analysis, and based on the residues
      in kidney, a withdrawal time of 4 days was estimated for marbofloxacin after oral
      administration at 5 mg/kg/day for three consecutive days. It was shown that
      population PBPK model could be used to accurately predict marbofloxacin residue
      withdrawal time in edible tissues in broiler chickens. 

PMID- 24903646
TI  - Toxoplasmic encephalitis associated with meningitis in a heart transplant
      recipient.
AB  - Toxoplasma gondii is an opportunistic pathogen that causes neurologic and
      extraneurologic manifestations in immunosuppressed patients. Encephalitis and
      intracranial mass lesions are easily recognized as typical manifestations of
      toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with
      very few cases described in the literature. We present the case of a heart
      transplant recipient who developed toxoplasmic encephalitis associated with
      meningitis. After an extensive review of the medical literature, we found only 1
      case of meningitis in solid organ transplant recipients and <25 cases in
      immunosuppressed patients, such as patients infected with human immunodeficiency
      virus or those with Hodgkin's disease. In this report, we consider toxoplasmosis
      in the differential diagnosis of meningitis in immunocompromised individuals. 

PMID- 24903647
TI  - Crystal structure and magnetism of Fe2(OH)[B2O4(OH)].
AB  - The structure and magnetism of Fe2(OH)[B2O4(OH)] are reported. Powder x-ray
      diffraction reveals a characteristic structure containing two
      crystallographically independent zigzag-ladder chains of magnetic Fe(2+) ions.
      Magnetization measurements reveal a phase transition at 85 K, below which a weak
      spontaneous magnetization (~ 0.15 MUB/Fe) appears. Below 85 K, magnetization
      increases with decreasing temperature down to 70 K, below which it decreases and
      approaches a constant value at low temperature. The Mossbauer spectrum at room
      temperature is composed of two paramagnetic doublets corresponding to the two
      crystallographic Fe(2+) sites. Below 85 K, each doublet undergoes further
      splitting because of the magnetic hyperfine fields. The temperature dependence of
      the hyperfine field is qualitatively different for the two distinguishable Fe(2+)
      sites. This is responsible for the anomalous temperature dependence of the
      magnetization.

PMID- 24903648
TI  - Paired single cell co-culture microenvironments isolated by two-phase flow with
      continuous nutrient renewal.
AB  - Cancer-stromal cell interactions are a critical process in tumorigenesis.
      Conventional dish-based assays, which simply mix two cell types, have limitations
      in three aspects: 1) limited control of the cell microenvironment; 2) inability
      to study cell behavior in a single-cell manner; and 3) have difficulties in
      characterizing single cell behavior within a highly heterogeneous cell population
      (e.g. tumor). An innovative use of microfluidic technology is for improving the
      spatial resolution for single cell assays. However, it is challenging to isolate
      the paired interacting cells while maintaining nutrient renewal. In this work,
      two-phase flow was used as a simple isolation method, separating the
      microenvironment of each individual chamber. As nutrients in an isolated chamber
      are consumed by cells, media exchange is required. To connect the cell culture
      chamber to the media exchange layer, we demonstrated a 3D microsystem integration
      technique using vertical connections fabricated by deep reactive-ion etching
      (DRIE). Compared to previous approaches, the presented process allows area
      reduction of vertical connections by an order of magnitude, enabling compact 3D
      integration. A semi-permeable membrane was sandwiched between the cell culture
      layer and the media exchange layer. The selectivity of the semi-permeable
      membrane results in the retention of the signaling proteins within the chamber
      while allowing free diffusion of nutrients (e.g., glucose and amino acids). Thus,
      paracrine signals are accumulated inside the chamber without cross-talk between
      cells in other chambers. Utilizing these innovations, we co-cultured UM-SCC-1
      (head and neck squamous cell carcinoma) cells and endothelial cells to simulate
      tumor proliferation enhancement in the vascular endothelial niche. 

PMID- 24903649
TI  - Platform for efficient switching between multiple devices in the intensive care
      unit.
AB  - INTRODUCTION: This article is part of the Focus Theme of METHODS of Information
      in Medicine on "Managing Interoperability and Complexity in Health Systems".
      OBJECTIVES: Handheld computers, such as tablets and smartphones, are becoming
      more and more accessible in the clinical care setting and in Intensive Care Units
      (ICUs). By making the most useful and appropriate data available on multiple
      devices and facilitate the switching between those devices, staff members can
      efficiently integrate them in their workflow, allowing for faster and more
      accurate decisions. This paper addresses the design of a platform for the
      efficient switching between multiple devices in the ICU. The key functionalities
      of the platform are the integration of the platform into the workflow of the
      medical staff and providing tailored and dynamic information at the point of
      care. METHODS: The platform is designed based on a 3-tier architecture with a
      focus on extensibility, scalability and an optimal user experience. After
      identification to a device using Near Field Communication (NFC), the appropriate
      medical information will be shown on the selected device. The visualization of
      the data is adapted to the type of the device. A web-centric approach was used to
      enable extensibility and portability. RESULTS: A prototype of the platform was
      thoroughly evaluated. The scalability, performance and user experience were
      evaluated. Performance tests show that the response time of the system scales
      linearly with the amount of data. Measurements with up to 20 devices have shown
      no performance loss due to the concurrent use of multiple devices. CONCLUSIONS:
      The platform provides a scalable and responsive solution to enable the efficient
      switching between multiple devices. Due to the web-centric approach new devices
      can easily be integrated. The performance and scalability of the platform have
      been evaluated and it was shown that the response time and scalability of the
      platform was within an acceptable range.

PMID- 24903650
TI  - Prenatal cocaine exposure and adolescent neural responses to appetitive and
      stressful stimuli.
AB  - Preclinical research has demonstrated the effects of prenatal cocaine exposure
      (PCE) on brain regions involved in emotional regulation, motivational control,
      and addiction vulnerability-eg, the ventral striatum (VS), anterior cingulate
      (ACC), and prefrontal cortex (PFC). However, little is known about the function
      of these regions in human adolescents with PCE. Twenty-two adolescents with PCE
      and 22 age-, gender-, and IQ-matched non-cocaine exposed (NCE) adolescents
      underwent functional magnetic resonance imaging (fMRI) during exposure to
      individually personalized neutral/relaxing, stressful, and favorite-food cues.
      fMRI data were compared using group-level two-tailed t-tests in the BioImage
      Suite. In comparison with NCE adolescents, PCE adolescents had reduced activity
      within cortical and subcortical brain regions, including the VS, ACC, and medial
      and dorslolateral PFC during exposure to favorite-food cues but did not differ in
      neural responses to stress cues. Subjective food craving was inversely related to
      dorsolateral PFC activation among PCE adolescents. Among PCE adolescents,
      subjective anxiety ratings correlated inversely with activations in the
      orbitofrontal cortex and brainstem during the stress condition and with ACC,
      dorsolateral PFC, and hippocampus activity during the neutral-relaxing condition.
      Thus adolescents with PCE display hypoactivation of brain regions involved in
      appetitive processing, with subjective intensities of craving and anxiety
      correlating inversely with extent of activation. These findings suggest possible
      mechanisms by which PCE might predispose to the development of addictions and
      related disorders, eg, substance-use disorders and binge-eating. 

PMID- 24903651
TI  - Rat nucleus accumbens core astrocytes modulate reward and the motivation to self
      administer ethanol after abstinence.
AB  - Our understanding of the active role that astrocytes play in modulating neuronal
      function and behavior is rapidly expanding, but little is known about the role
      that astrocytes may play in drug-seeking behavior for commonly abused substances.
      Given that the nucleus accumbens is critically involved in substance abuse and
      motivation, we sought to determine whether nucleus accumbens astrocytes influence
      the motivation to self-administer ethanol following abstinence. We found that the
      packing density of astrocytes that were expressing glial fibrillary acidic
      protein increased in the nucleus accumbens core (NAcore) during abstinence from
      EtOH self-administration. No change was observed in the nucleus accumbens shell.
      This increased NAcore astrocyte density positively correlated with the motivation
      for ethanol. Astrocytes can communicate with one another and influence neuronal
      activity through gap-junction hemichannels. Because of this, the effect of
      blocking gap-junction hemichannels on the motivation for ethanol was examined.
      The motivation to self-administer ethanol after 3 weeks abstinence was increased
      following microinjection of gap-junction hemichannel blockers into the NAcore at
      doses that block both neuronal and astrocytic channels. In contrast, no effect
      was observed following microinjection of doses that are not thought to block
      astrocytic channels or following microinjection of either dose into the nucleus
      accumbens shell. Additionally, the motivation for sucrose after 3 weeks
      abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next,
      Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were
      selectively expressed in NAcore astrocytes to test the effect of astrocyte
      stimulation. DREADD activation increased cytosolic calcium in primary astrocytes,
      facilitated responding for rewarding brain stimulation, and reduced the
      motivation for ethanol after 3 weeks abstinence. This is the first work to
      modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together,
      our findings demonstrate that NAcore astrocytes can shape the motivation to self
      administer ethanol; suggesting that the development of ligands which selectively
      stimulate astrocytes may be a successful strategy to abate ethanol-seeking
      behavior. 

PMID- 24903652
TI  - Cellular and behavioral outcomes of dorsal striatonigral neuron ablation: new
      insights into striatal functions.
AB  - The striatum is the input structure of the basal ganglia network that contains
      heterogeneous neuronal populations, including two populations of projecting
      neurons called the medium spiny neurons (MSNs), and different types of
      interneurons. We developed a transgenic mouse model enabling inducible ablation
      of the striatonigral MSNs constituting the direct pathway by expressing the human
      diphtheria toxin (DT) receptor under the control of the Slc35d3 gene promoter, a
      gene enriched in striatonigral MSNs. DT injection into the striatum triggered
      selective elimination of the majority of striatonigral MSNs. DT-mediated ablation
      of striatonigral MSNs caused selective loss of cholinergic interneurons in the
      dorsal striatum but not in the ventral striatum (nucleus accumbens), suggesting a
      region-specific critical role of the direct pathway in striatal cholinergic
      neuron homeostasis. Mice with DT injection into the dorsal striatum showed
      altered basal and cocaine-induced locomotion and dramatic reduction of L-DOPA
      induced dyskinesia in the parkinsonian condition. In addition, these mice
      exhibited reduced anxiety, revealing a role of the dorsal striatum in the
      modulation of behaviors involving an emotional component, behaviors generally
      associated with limbic structures. Altogether, these results highlight the
      implication of the direct striatonigral pathway in the regulation of
      heterogeneous functions from cell survival to regulation of motor and emotion
      associated behaviors. 

PMID- 24903653
TI  - Epidemiology of metastatic hepatocellular carcinoma, a nationwide perspective.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary tumor of
      the liver. AIMS: The aim of this study was to describe the prevalence, trends,
      and predictors of metastatic HCC on a national scale. METHODS: We used two
      nationwide datasets for our study: the University Health Consortium (UHC) and the
      Nationwide Inpatient Sample (NIS) databases. We included adults with a primary
      diagnosis of HCC from 2000 to 2011. We collected information regarding
      demographics, insurance, HCC risk factors, liver decompensation, and the sites
      and frequencies of metastases. Multivariable regression analysis was used to
      examine predictors of metastatic HCC. Trend analysis was performed to examine the
      change in metastatic HCC prevalence over time. RESULTS: We included 25,671 and
      26,054 HCC patients from UHC and NIS, respectively. Prevalence of metastatic HCC
      was 18 % with lung being the most frequent site (31 %). Compared with Caucasian,
      African American ethnicity was an independent predictor of metastasis in both the
      NIS [OR 1.13 (1.02-1.25)] and UHC [OR 1.4 (1.3-1.6)] databases. Lack of long-term
      insurance was associated with significantly higher prevalence of metastasis in
      both the NIS [OR 1.6 (1.4-1.9)] and UHC [OR 1.9 (1.6-2.2)] databases. There has
      been an increased prevalence of metastatic HCC over the last decade with an
      annual percentage change of +1.25 and +1.60 % (p = 0.03 and p = 0.08) for the NIS
      and UHC databases, respectively. CONCLUSIONS: Metastasis is not rare among HCC
      patients and is rising in prevalence over the last decade. Lungs were the most
      common metastatic site. Ethnicity and insurance status are independent predictors
      of metastasis.

PMID- 24903654
TI  - Selective Versus Universal Screening for Lynch Syndrome: A Six-Year Clinical
      Experience.
AB  - BACKGROUND: Lynch syndrome is the most common cause of hereditary colorectal
      cancer (CRC) and confers increased risk of other cancers. Identification of
      patients improves morbidity and mortality. Screening tumors for absent mismatch
      repair (MMR) protein expression by immunohistochemistry (IHC) is a recommended
      approach. Despite guidelines advocating universal screening, significant
      variation in clinical practice exists. AIMS/METHODS: A retrospective study of two
      different IHC-based Lynch syndrome screening protocols at an urban, university
      hospital was performed. Outcomes from a "selective" screening strategy utilized
      from August 2007-July 2010 on CRC tumors from patients with high-risk features
      were compared with a "universal" strategy of screening all CRC tumors from July
      2010-August 2013. Positively screened patients were referred for genetic
      counseling and offered germline testing. RESULTS: A total of 392 patients with
      CRC were screened: 107 selectively and 285 universally. The prevalence of Lynch
      syndrome was 3.1 %, with no difference by strategy. There was a trend (p = 0.06)
      toward fewer universally screened patients agreeing to genetic counseling
      compared with those selectively screened. Selective criteria failed to identify
      one of eight cases of Lynch syndrome from the universal group, though the
      universal strategy screened 166 additional tumors to find this additional
      patient. CONCLUSIONS: Selective screening for Lynch syndrome has similar outcomes
      as universal screening in terms of identifying Lynch syndrome, despite screening
      far fewer patients. In addition, fewer eligible patients in our study agreed to
      undergo genetic counseling and germline testing than in prior studies. These
      lower rates may better reflect uptake of these services in clinical practice.

PMID- 24903655
TI  - [Recommendations for use of abatacept in patients with rheumatoid arthritis].

PMID- 24903656
TI  - Clinical and laboratory profiles of 136 systemic sclerosis patients with and
      without echocardiographically detected pulmonary hypertension.
AB  - AIM: This study aims to review the clinical and laboratory profiles of systemic
      sclerosis (SSc) patients with and without echocardiographically detected
      pulmonary hypertension (PH) in China. PATIENTS AND METHODS: The study included
      136 consecutive patients treated from 1992 to 2012. Diagnosis of SSc was made
      according to the 1980 revision of the American College of Rheumatology SSc
      criteria. PH was defined as systolic pulmonary artery pressure >= 40 mmHg
      detected by Doppler echocardiography. The clinical and laboratory parameters of
      SSc patients with pulmonary hypertension (SSc-PH) were compared to those of SSc
      patients without pulmonary hypertension (SSc-no PH). RESULTS: Of the 136 SSc
      patients, 28 (20.6 %) were diagnosed as having PH by echocardiography. Upon
      comparison with the SSc-no PH patients, SSc-PH patients were observed to have a
      significantly higher frequency of subjective dyspnea (P = 0.010) and a higher
      rate of anti-nuclear RNP (anti-nRNP) antibody positivity (P = 0.028). We also
      observed that the percentage of SSc-PH patients with increased urea nitrogen is
      significantly higher than that of SSc-no PH patients after correction for
      multiple testing (P = 0.006, compared to patients with normal values).
      CONCLUSION: This study demonstrates that SSc patients with PH detected by
      echocardiography had characteristic clinical and laboratory features. More
      specific treatment addressing these aspects should be offered to improve the
      curative effect of therapy in SSc-PH patients.

PMID- 24903657
TI  - Dynamic equilibrium of heterogeneous and interconvertible multipotent
      hematopoietic cell subsets.
AB  - Populations of hematopoietic stem cells and progenitors are quite heterogeneous
      and consist of multiple cell subsets with distinct phenotypic and functional
      characteristics. Some of these subsets also appear to be interconvertible and
      oscillate between functionally distinct states. The multipotent hematopoietic
      cell line EML has emerged as a unique model to study the heterogeneity and
      interconvertibility of multipotent hematopoietic cells. Here we describe
      extensive phenotypic and functional heterogeneity of EML cells which stems from
      the coexistence of multiple cell subsets. Each of these subsets is phenotypically
      and functionally heterogeneous, and displays distinct multilineage
      differentiation potential, cell cycle profile, proliferation kinetics, and
      expression pattern of HSC markers and some of the key lineage-associated
      transcription factors. Analysis of their maintenance revealed that on a
      population level all EML cell subsets exhibit cell-autonomous interconvertible
      properties, with the capacity to generate all other subsets and re-establish
      complete parental EML cell population. Moreover, all EML cell subsets generated
      during multiple cell generations maintain their distinct phenotypic and
      functional signatures and interconvertible properties. The model of EML cell line
      suggests that interconvertible multipotent hematopoietic cell subsets coexist in
      a homeostatically maintained dynamic equilibrium which is regulated by currently
      unknown cell-intrinsic mechanisms. 

PMID- 24903658
TI  - Reference ranges of kidney dimensions in term newborns: sonographic measurements.
AB  - BACKGROUND: Ultrasonographic measurement of kidney dimensions is important in
      evaluation of renal disease during the neonatal period, when renal abnormalities
      are common and renal size rapidly changes with age. OBJECTIVE: To determine the
      reference ranges of kidney dimensions in newborns and to provide a reference
      chart for daily practice. MATERIALS AND METHODS: In this prospective study,
      kidney dimensions were evaluated in 385 healthy newborns with a gestational age
      >=37 weeks. Each neonate seen at an obstetrics clinic and neonatal intensive care
      unit was examined with sonography within the first week of life. Relationships of
      all dimensions with gender, gestational age, height and weight were statistically
      analyzed. RESULTS: All dimensions of the kidneys were smaller in girls than in
      boys (P < 0.05). The dimensions of the left kidney were larger than those in the
      right kidney in both genders (P < 0.01). Longitudinal and anteroposterior
      dimensions of the right and left kidneys showed no correlation with the
      gestational age in either gender. The dimensions correlated with the height in
      boys (P < 0.01), while no correlation was seen between the dimensions and height
      in girls (P < 0.05). Weight had the best correlation with all dimensions in both
      genders. CONCLUSION: The reference values of kidney lengths and diagrams from
      this study may be useful in the sonographic evaluation of kidneys in newborns.

PMID- 24903659
TI  - Accuracy of abdominal ultrasound and MRI for detection of Crohn disease and
      ulcerative colitis in children.
AB  - BACKGROUND: Endoscopy is currently the primary diagnostic technique for
      inflammatory bowel disease (IBD) in children. OBJECTIVE: To assess the accuracy
      of US and dynamic contrast-enhanced MRI for diagnosing inflammatory bowel disease
      and for distinguishing Crohn disease and ulcerative colitis in comparison to a
      reference standard. MATERIALS AND METHODS: Consecutive children with suspected
      IBD underwent diagnostic workup including ileocolonoscopy and upper
      gastrointestinal endoscopy as the reference standard, abdominal US, and MR
      enterography and colonography at 3 T. The protocol included a dynamic contrast
      enhanced 3-D sequence. Sensitivity, specificity and kappa values were calculated
      for one ultrasonographer and two MRI observers. RESULTS: We included 28 children
      (15 boys) with mean age 14 years (range 10-17 years). The diagnosis was IBD in 23
      children (72%), including 12 with Crohn disease, 10 with ulcerative colitis and 1
      with indeterminate colitis. For the diagnosis of inflammatory bowel disease the
      sensitivity was 55% for US and 57% (both observers) for MR entero- and
      colonography, and the specificity was 100% for US and 100% (observer 1) and 75%
      (observer 2) for MR entero- and colonography. Combined MRI and US had sensitivity
      and specificity of 70% and 100% (observer 1) and 74% and 80% (observer 2),
      respectively. With the addition of a dynamic contrast-enhanced MR sequence, the
      sensitivity increased to 83% and 87%. US and MRI could only distinguish between
      Crohn disease and ulcerative colitis when terminal ileum lesions were present.
      CONCLUSION: US and MR entero- and colonography have a high accuracy for
      diagnosing inflammatory bowel disease in children but cannot be used to
      distinguish Crohn disease and ulcerative colitis.

PMID- 24903660
TI  - False-positive In-111 DTPA octreotide scintigraphy in bilateral tibial
      insufficiency fracture.
AB  - We present a case of bilateral tibial insufficiency fracture in which indium (In)
      111 diethylenetriamine pentaacetic acid (DTPA) octreotide scan showed increased
      activity in the region of the fracture. The scan was performed in a 5-year-old
      girl with severe refractory hypertension and elevated plasma metanephrines for
      evaluation of possible neuroendocrine tumor. Octreotide scan is usually positive
      in neuroendocrine and some other tumors but also shows positive results in a
      number of other conditions. However insufficiency fracture has not been reported
      as a positive finding on octreotide scan in children. This may relate to the
      expression of somatostatin membrane receptor in activated white blood cells or
      expression of somatostatin receptors by bone cells. 

PMID- 24903661
TI  - Management of functional epiphora in patients with an anatomically patent
      dacryocystorhinostomy.
AB  - IMPORTANCE: Approximately 5% to 10% of patients continue to experience persistent
      epiphora following an anatomically successful dacryocystorhinostomy (DCR) for
      nasolacrimal duct obstruction or stenosis. OBJECTIVE: To investigate the
      management and success rate of so-called "functional failure" of DCR for
      nasolacrimal duct obstruction by experienced lacrimal surgeons. DESIGN, SETTING,
      AND PARTICIPANTS: Multicenter retrospective case series including 5 Australian
      and New Zealand centers. Participants included 61 patients (71% women [n = 46];
      mean age, 66 years) with functional epiphora after 65 DCRs (69% transnasal) who
      were recruited over a mean of 7.6 years. Inclusion criteria included confirmed
      preoperative diagnosis of nasolacrimal duct obstruction or stenosis, age greater
      than 18 years, recurrent or persistent epiphora after DCR, an anatomically
      successful DCR, and follow-up longer than 6 months. Exclusion criteria included
      evidence of lacrimal hypersecretion, eyelid malposition, and punctal or
      canalicular abnormalities. MAIN OUTCOMES AND MEASURES: The number, type, timing,
      and success of all clinical interventions performed for the management of
      functional epiphora after DCR. RESULTS: Epiphora recurred a mean of 8.9 months
      after primary DCR; 89% of the cases (n = 58) had evidence of a patent ostium and
      100% were patent on lacrimal irrigation. Intubation with a lacrimal stent was
      performed in 82% of the cases at the time of surgery, and all stents were removed
      a mean of 8 weeks postoperatively. Epiphora was reported immediately following
      DCR in 32% (n = 21) of the cases and within 6 weeks after removal of the stent in
      31% (n = 20); late recurrence (>12 months after DCR) developed in 37% (n = 24) of
      the cases. In a total of 15% of the cases, participants declined any treatment
      following DCR. The remainder underwent a mean of 1.3 interventions (range, 1-3)
      during a mean of 23 to 41 months after primary DCR, following which 72% (n = 47)
      of the cases had a successful outcome; 12% (n = 8) failed to achieve improvement,
      and the patients declined further intervention. Thirty-nine interventions (60%)
      were intubation with a silicone stent with a 54% success rate. Almost half of
      those undergoing intubation elected to keep the stent permanently; 34% (n = 22)
      had an eyelid-tightening procedure with 50% success, and 15% (n = 10) required a
      Lester-Jones tube despite patent canaliculi, with a success rate of 90%.
      CONCLUSIONS AND RELEVANCE: Functional epiphora after DCR among patients with
      preoperative nasolacrimal duct obstruction or stenosis appears to be uncommon.
      Benefits can be achieved in most patients with intubation (transient or
      permanent) or eyelid tightening. More than one procedure is often required.

PMID- 24903662
TI  - A nuclear transport inhibitor that modulates the unfolded protein response and
      provides in vivo protection against lethal dengue virus infection.
AB  - BACKGROUND: Dengue virus (DENV) is estimated to cause 390 million infections each
      year, but there is no licensed vaccine or therapeutic currently available.
      METHODS: We describe a novel, high-throughput screen to identify compounds
      inhibiting the interaction between DENV nonstructural protein 5 and host nuclear
      transport proteins. We document the antiviral properties of a lead compound
      against all 4 serotypes of DENV, antibody-dependent enhanced (ADE) infection, and
      ex vivo and in vivo DENV infections. In addition, we use quantitative reverse
      transcription polymerase chain reaction to examine cellular effects upon compound
      addition. RESULTS: We identify N-(4-hydroxyphenyl) retinamide (4-HPR) as
      effective in protecting against DENV-1-4 and DENV-1 ADE infections, with 50%
      effective concentrations in the low micromolar range. 4-HPR but not the closely
      related N-(4-methoxyphenyl) retinamide (4-MPR) could reduce viral RNA levels and
      titers when applied to an established infection. 4-HPR but not 4-MPR was found to
      specifically upregulate the protein kinase R-like endoplasmic reticulum kinase
      arm of the unfolded protein response. Strikingly, 4-HPR but not 4-MPR restricted
      infection in peripheral blood mononuclear cells and in a lethal ADE-infection
      mouse model. CONCLUSIONS: 4-HPR is a novel antiviral that modulates the unfolded
      protein response, effective against DENV1-4 at concentrations achievable in the
      plasma in a clinical setting, and provides protection in a lethal mouse model.

PMID- 24903663
TI  - Respiratory syncytial virus transplacental antibody transfer and kinetics in
      mother-infant pairs in Bangladesh.
AB  - BACKGROUND: Pneumonia is the leading cause of childhood mortality globally.
      Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia.
      Maternal serum antibody protects infants from RSV disease. The objective of our
      study was to characterize RSV antibody levels in mother-infant pairs. METHODS:
      Serial serum samples were collected from mother-infant pairs in Bangladesh from
      the third trimester of pregnancy to 72 weeks postpartum and tested using an RSV
      antibody microneutralization assay. Serologic infection was defined as a 4-fold
      increase in antibody titer. Maternal antibody half-life was calculated using
      infant antibody titers from birth to 20 weeks. RESULTS: The ratio of infant cord
      blood to maternal serum RSV antibody titers in 149 mother-infant pairs was 1.01
      (95% confidence interval [CI], .99-1.03). Maternal RSV antibody titers in the
      third trimester and at birth were strongly correlated (R = 0.68). Antibody half
      life was 38 days (95% CI, 36-42 days). Higher cord blood RSV antibody titers were
      associated with a lower risk of serologic infection (P = .01) and maintenance of
      antibody titer above a potentially protective threshold (P < .001). CONCLUSIONS:
      Efficient transplacental transfer of RSV-specific antibody from mother to the
      fetus was documented in mother-infant pairs in Asia. Higher cord blood antibody
      titers were associated with protection from serologic infection.

PMID- 24903664
TI  - Estimating the effectiveness of tetanus-diphtheria-acellular pertussis vaccine
      (Tdap) for preventing pertussis: evidence of rapidly waning immunity and
      difference in effectiveness by Tdap brand.
AB  - BACKGROUND: We estimated the vaccine effectiveness (VE) of tetanus-diphtheria
      acellular pertussis vaccine (Tdap) for preventing pertussis among adolescents
      during a statewide outbreak of pertussis in Wisconsin during 2012. METHODS: We
      used the population-based Wisconsin Immunization Registry (WIR) to construct a
      cohort of Wisconsin residents born during 1998-2000 and collect Tdap vaccination
      histories. Reports of laboratory-confirmed pertussis with onset during 2012 were
      matched to WIR clients. Incidence rate ratios (IRRs) of pertussis and Tdap VE
      estimates [(1 - IRR)*100%], by year of Tdap vaccine receipt and brand
      (Boostrix/Adacel), were estimated using Poisson regression. RESULTS: Tdap VE
      decreased with increasing time since receipt, with VEs of 75.3% (95% confidence
      interval [CI], 55.2%-86.5%) for receipt during 2012, 68.2% (95% CI, 60.9%-74.1%)
      for receipt during 2011, 34.5% (95% CI, 19.9%-46.4%) for receipt during 2010, and
      11.9% (95% CI, -11.1% to 30.1%) for receipt during 2009/2008; point estimates
      were higher among Boostrix recipients than among Adacel recipients. Among Tdap
      recipients, increasing time since receipt was associated with increased risk, and
      receipt of Boostrix (vs Adacel) was associated with decreased risk of pertussis
      (adjusted IRR, 0.62 [95% CI, .52-.74]). CONCLUSIONS: Our results demonstrate
      waning immunity following vaccination with either Tdap brand. Boostrix was more
      effective than Adacel in preventing pertussis in our cohort, but these findings
      may not be generalizable to adolescent cohorts that received different diphtheria
      tetanus-acellular pertussis vaccines (DTaP) during childhood and should be
      further examined in studies that include childhood DTaP history.

PMID- 24903665
TI  - Molecular evidence of Wolbachia endosymbiosis in Mansonella perstans in Gabon,
      Central Africa.
AB  - The discovery of obligatory intracellular bacteria of the genus Wolbachia in
      filariae infecting humans led to the use of antibiotics as a potent treatment
      option. Mansonella perstans is the cause of the second most prevalent filariasis
      in Gabon, but so far reports on the presence of Wolbachia in this nematode have
      been inconsistent. We report on the presence of Wolbachia in M. perstans in
      patients from Gabon, which we identified using polymerase chain reaction (PCR)
      with primer sets specific for 16S rDNA and ftsZ. Sequence analysis revealed a
      single consensus sequence, which could be phylogenetically assigned to Wolbachia
      of the supergroup F. Wolbachia could only be identified in 5 of 14 or 7 of 14
      cases, depending on the investigated gene; detection of Wolbachia was associated
      with higher-level filaremia. Before generalizing the use of antibiotics for
      mansonellosis, further clarification of the obligatory nature of the
      endosymbiosis in this nematode is needed. 

PMID- 24903667
TI  - Frailty in people aging with human immunodeficiency virus (HIV) infection.
AB  - The increasing life spans of people infected with human immunodeficiency virus
      (HIV) reflect enormous treatment successes and present new challenges related to
      aging. Even with suppression of viral loads and immune reconstitution, HIV
      positive individuals exhibit excess vulnerability to multiple health problems
      that are not AIDS-defining. With the accumulation of multiple health problems, it
      is likely that many people aging with treated HIV infection may be identified as
      frail. Studies of frailty in people with HIV are currently limited but suggest
      that frailty might be feasible and useful as an integrative marker of multisystem
      vulnerability, for organizing care and for comprehensively measuring the impact
      of illness and treatment on overall health status. This review explains how
      frailty has been conceptualized and measured in the general population,
      critically reviews emerging data on frailty in people with HIV infection, and
      explores how the concept of frailty might inform HIV research and care. 

PMID- 24903668
TI  - The significance of transplacental antibody against respiratory syncytial virus.

PMID- 24903666
TI  - Antigen-presenting phagocytic cells ingest malaria parasites and increase HIV
      replication in a tumor necrosis factor alpha-dependent manner.
AB  - BACKGROUND: Plasmodium falciparum infection induces human immunodeficiency virus
      (HIV) replication and accelerates a decline in CD4(+) T-cell count. The
      mechanisms contributing to these interactions have not been fully elucidated.
      METHODS: We infected peripheral blood mononuclear cells (PBMCs) with HIV type 1
      (HIV-1) and then cocultured them with P. falciparum-infected red blood cells
      (iRBCs) or uninfected RBCs (uRBCs). Levels of HIV-1 p24 antigen and activation
      associated cytokines were measured in culture supernatants. T-cell surface
      activation was assessed by flow cytometry. RESULTS: It has been reported that
      iRBCs increase HIV replication, compared with uRBCs; that neutralizing tumor
      necrosis factor alpha (TNF-alpha) abrogates this increase; and that hemozoin
      enhances HIV production. In this study, we confirmed that TNF-alpha plays an
      important role in this interaction. We show that iRBCs increased CD4(+) T-cell
      expression of HLA-DR(+)/CD38(+) (P = .001), that monocyte/macrophage depletion
      reduced HIV production by 40%-50% (P < .001), and that hemozoin-laden
      monocytes/macrophages that were preincubated with iRBCs also stimulated HIV
      production. CONCLUSIONS: iRBCs activate CD4(+) T cells and stimulate HIV
      replication in a TNF-alpha-dependent manner following malarial antigen processing
      by monocytes/macrophages. These results suggest that the persistent elevation of
      HIV replication during and after acute bouts of P. falciparum malaria may be due,
      at least in part, to ongoing stimulation of CD4(+) T cells by hemozoin-loaded
      antigen-presenting cells within lymphoid tissues.

PMID- 24903669
TI  - Factors underlying the success of behavioral HIV-prevention interventions for
      adolescents: a meta-review.
AB  - The purpose of this meta-review was to identify characteristics of successful HIV
      prevention interventions for adolescents based on quantitative (i.e., meta
      analyses) and qualitative reviews published to date, and to inform intervention
      utilization and future development. To that end, we were guided by principles of
      triangulation. Searches of seven electronic bibliographic databases yielded five
      meta-analyses and six qualitative reviews that satisfied the selection criteria.
      Reviews were subjected to careful content analysis. All reviews reported that
      behavioral interventions had positive outcomes on at least one of the following
      outcomes: HIV-related knowledge, subjective cognitions and beliefs enabling safer
      sex, abstinence, delaying next sexual intercourse, decreasing number of sexual
      partners, and actual condom use. Four categories, suggesting factors more
      prominently linked to intervention success, emerged: behavior change techniques
      (e.g., cognitive-behavior and motivation enhancement skills training); recipient
      characteristics (e.g., age, vulnerability to contracting STIs/HIV); prominent
      design features (e.g., use of theory, formative research); and socio-ecological
      features (e.g., supportive school environment). Future interventions would
      benefit from conducting preliminary formative research in order to enable optimal
      implementation of all these factors.

PMID- 24903670
TI  - Visual acuity and central retinal thickness: fulfilment of retreatment criteria
      for recurrent neovascular AMD in routine clinical care.
AB  - BACKGROUND: To evaluate the fulfillment of retreatment criteria in recurrent
      neovascular age-related macular degeneration (nAMD) for a pro-re-nata treatment
      regime with ranibizumab in routine clinical care. METHODS: Data from patients
      with treatment-naive nAMD were analysed retrospectively. As an 'upload', all
      patients had received three-monthly intravitreal ranibizumab injections in a
      university eye hospital and were then seen by ophthalmologists in private
      practice who referred them back in case of recurrence. Recurrence was defined as
      a decrease of visual acuity (VA) of one line or more (functional retreatment
      criteria), a central retinal thickness (CRT) increase of at least 100 um upon
      Optical Coherence Tomography (OCT) examination (morphological retreatment
      criteria) or a new macular haemorrhage (clinical retreatment criteria). RESULTS:
      We included 92 patients (36 men and 56 women). The mean VA before retreatment of
      a recurrence was -0.63 +/- 0.33 logMAR and improved significantly (p<0.001) by
      0.10 +/- 0.16 logMAR to -0.53 +/- 0.28 logMAR thereafter. Mean CRT before
      retreatment was 278.07 +/- 87.56 um and decreased significantly (p<0.001) by
      71.22 +/- 106.93 to 206.85 +/- 60.30 um. Evaluation of the fulfillment of
      retreatment criteria revealed functional retreatment criteria in 82.6% of
      patients. However, upon re-evaluation of VA using Early Treatment Diabetic
      Retinopathy Study (ETDRS) charts in the treatment centre, mean decrease of VA was
      10 letters as compared with the end of upload therapy. All patients presented an
      increased CRT when treated for recurrence of nAMD (mean increase 69.47 um), but
      the morphological retreatment criteria (CRT increase of 100 um or more) were
      fulfilled in only 44.4% of patients upon Spectral Domain OCT (SD-OCT) evaluation
      in the treatment centre. CONCLUSIONS: In a routine clinical care, evaluation of
      VA using ETDRS charts seems to be more sensitive than Snellen VA testing.
      Quantitative OCT-based retreatment criteria (eg, increase of CRT of 100 um or
      more) appear to be not sensitive enough in a clinical setting with referring
      ophthalmologists.

PMID- 24903671
TI  - Towards improving the ethics of ecological research.
AB  - We argue that the ecological research community should develop a plan for
      improving the ethical consistency and moral robustness of the field. We propose a
      particular ethics strategy--specifically, an ongoing process of collective
      ethical reflection that the community of ecological researchers, with the
      cooperation of applied ethicists and philosophers of biology, can use to address
      the needs we identify. We suggest a particular set of conceptual (in the form of
      six core values--freedom, fairness, well being, replacement, reduction, and
      refinement) and analytic (in the forms of decision theoretic software, 1000Minds)
      tools that, we argue, collectively have the resources to provide an empirically
      grounded and conceptually complete foundation for an ethics strategy for
      ecological research. We illustrate our argument with information gathered from a
      survey of ecologists conducted at the 2013 meeting of the Canadian Society of
      Ecology and Evolution.

PMID- 24903672
TI  - Foamy cell (hibernoma-like) change is a rare histopathological feature in renal
      cell carcinoma.
AB  - We report nine patients (seven males and two females, median age 64 years (range
      51-79 years)) with a renal cell carcinoma, each of which contained a significant
      component of neoplastic epithelial cells with a striking microvacuolated
      (hibernoma-like) cytoplasmic appearance. Tumor sizes ranged from 1.5 to 8.0 cm
      (mean 4.2 cm, median 4.3 cm). The basic architecture of the tumors was solid
      alveolar in two cases (classified as renal cell carcinoma-not otherwise specified
      (NOS)) and papillary in seven cases (classified as papillary renal cell carcinoma
      NOS). The nuclear grade according to the Fuhrman grading system was three in all
      cases. By immunohistochemistry, the cells with microvacuolated cytopasm and
      significantly expressed adipophilin and anti-mitochondrial antigen in a similar
      cytoplasmic pattern. On ultrastructural examination, the cytoplasm of the
      neoplastic epithelial cells was packed with distended mitochondria, most of which
      displayed lamellated cristae. Numerous microvesicles were dispersed between the
      mitochondria. No mutations in the succinate dehydrogenase B gene were identified.
      Based on our findings, we propose that the mechanism behind this phenomenon is an
      abnormal intracellular processing of lipids. No aggressive behavior was observed
      in six out of nine patients with available follow-up information.

PMID- 24903673
TI  - Fibromatosis-like metaplastic carcinoma of the breast has a claudin-low
      immunohistochemical phenotype.
AB  - Fibromatosis-like metaplastic carcinoma (FLMCa) of the breast is a rare low-grade
      spindle cell carcinoma, of which the biological characteristics have not been
      well studied. This study aims to assess, in FLMCa, immunohistochemical expression
      of claudins (CLDN) and features connected with the claudin-low subtype, such as
      the presence of tumor initiating cells (TIC), epithelial-mesenchymal transition
      (EMT) phenotype, as well as EGFR activating mutations. Three cases of FLMCa were
      retrieved from our hospital archives. Histological and immunohistochemical
      characteristics were reviewed. Expression of CLDN-1, CLDN-3, CLDN-4 and CLDN-7,
      CD44 and CD24 (TIC phenotype), and vimentin and E-cadherin (EMT features) were
      studied. EGFR mutations on exons 18, 19, 20, and 21 were investigated by real
      time PCR. In all cases, the low-grade spindle cell component was predominant,
      with two cases presenting <5 % of epithelioid and squamous areas. The tumors
      expressed basal cytokeratins and vimentin and were hormone receptor and ERBB2
      negative. CLDN membrane expression was negative in the spindle cell component.
      The epithelioid areas were CLDN-1 positive. Nuclear/cytoplasmatic expression of
      CLDN-4 was observed in all components, except in one case in which it was
      strongly expressed in the non-spindle areas. All three cases were CD44+/CD24-. E
      cadherin was focally expressed in epithelioid cells, only in the squamous areas.
      Activating EGFR mutations were not found. One patient developed local
      recurrences, metastases and died. FLMCa have the immunohistochemical profile of
      claudin-low breast tumors, with low expression of adhesion molecules, presence of
      TIC and EMT phenotype. No EGFR activating mutations were found.

PMID- 24903674
TI  - Open questions: what has genetics told us about autism spectrum disorders?
AB  - Some of the most interesting questions in biology today, in my view, derive from
      the real advances in neuropsychiatry that have come largely from human genetics.
      Research in autism spectrum disorders (ASDs) has been leading the way, mainly
      because it has become especially well funded and has recently attracted many
      outstanding scientists. (I must make it clear that I am an outsider in this
      field, as I have never worked on any neuropsychiatric disorder). 

PMID- 24903675
TI  - Experiences of racism, racial/ethnic attitudes, motivated fairness and mental
      health outcomes among primary and secondary school students.
AB  - While studies investigating the health effects of racial discrimination for
      children and youth have examined a range of effect modifiers, to date,
      relationships between experiences of racial discrimination, student attitudes,
      and health outcomes remain unexplored. This study uniquely demonstrates the
      moderating effects of vicarious racism and motivated fairness on the association
      between direct experiences of racism and mental health outcomes, specifically
      depressive symptoms and loneliness, among primary and secondary school students.
      Across seven schools, 263 students (54.4% female), ranging from 8 to 17 years old
      (M = 11.2, SD = 2.2) reported attitudes about other racial/ethnic groups and
      experiences of racism. Students from minority ethnic groups (determined by
      country of birth) reported higher levels of loneliness and more racist
      experiences relative to the majority group students. Students from the majority
      racial/ethnic group reported higher levels of loneliness and depressive symptoms
      if they had more friends from different racial/ethnic groups, whereas the number
      of friends from different groups had no effect on minority students' loneliness
      or depressive symptoms. Direct experiences of racism were robustly related to
      higher loneliness and depressive symptoms in multivariate regression models.
      However, the association with depressive symptoms was reduced to marginal
      significance when students reported low motivated fairness. Elaborating on the
      negative health effects of racism in primary and secondary school students
      provides an impetus for future research and the development of appropriate
      interventions.

PMID- 24903676
TI  - The anti-seizure drugs vinpocetine and carbamazepine, but not valproic acid,
      reduce inflammatory IL-1beta and TNF-alpha expression in rat hippocampus.
AB  - In the present study, the effects of the two classical anti-epileptic drugs,
      carbamazepine and valproic acid, and the non-classical anti-seizure drug
      vinpocetine were investigated on the expression of the pro-inflammatory cytokines
      IL-1beta and TNF-alpha in the hippocampus of rats by PCR or western blot after
      the administration of one or seven doses. Next, the effects of the anti-seizure
      drugs were investigated on the rise in cytokine expression induced by
      lipopolysaccharides (LPS) inoculation in vivo. To validate our methods, the
      changes induced by the pro-convulsive agents 4-aminopyridine, pentylenetetrazole
      and pilocarpine were also tested. Finally, the effect of the anti-seizure drugs
      on seizures and on the concomitant rise in pro-inflammatory cytokine expression
      induced by 4-aminopyridine was explored. Results show that vinpocetine and
      carbamazepine reduced the expression of IL-1beta and TNF-alpha from basal
      conditions, and the increase in both pro-inflammatory cytokines induced by LPS.
      In contrast, valproic acid failed to reduce both the expression of the cytokines
      from basal conditions and the rise in IL-1beta and TNF-alpha expression induced
      by LPS. Tonic-clonic seizures induced either by 4-aminopyridine,
      pentylenetetrazole or pilocarpine increased the expression of IL-1beta and TNF
      alpha markedly. 4-aminopyridine-induced changes were reduced by all the tested
      anti-seizure drugs, although valproic acid was less effective. We conclude that
      the anti-seizure drugs, vinpocetine and carbamazepine, whose mechanisms of action
      involve a decrease in ion channels permeability, also reduce cerebral
      inflammation. The mechanism of action of anti-seizure drugs like vinpocetine and
      carbamazepine involves a decrease in Na(+) channels permeability. We here propose
      that this mechanism of action also involves a decrease in cerebral inflammation. 

PMID- 24903677
TI  - A comprehensive immunophenotypic marker analysis of hairy cell leukemia in
      paraffin-embedded bone marrow trephine biopsies--a tissue microarray study.
AB  - Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferation characterized
      by a unique immunophenotype. Due to low number of circulating neoplastic cells
      and 'dry tap' aspiration, the diagnosis is often based on BM trephine biopsy. We
      have performed a consecutive immunohistochemical analysis to evaluate diagnostic
      usefulness of various HCL markers (CD11c, CD25, CD68, CD103, CD123, CD200,
      annexin A1, cyclin D1, DBA.44, HBME-1, phospho-ERK1/2, TRAP, and T-bet) currently
      available against fixation resistant epitopes. We analyzed tissue microarrays
      consisting of samples gained from 73 small B-cell lymphoma cases, including hairy
      cell leukemia (HCL) (n = 32), HCL variant (HCL-v) (n = 4), B-cell chronic
      lymphocytic leukemia (B-CLL) (n = 11), lymphoplasmacytic lymphoma (LPL) (n = 3),
      mantle cell lymphoma (MCL) (n = 10), splenic diffuse red pulp small B cell
      lymphoma (SDRPL) (n = 2), splenic B cell marginal zone lymphoma (SMZL) (n = 8),
      and splenic B cell lymphoma/leukemia, unclassifiable (SBCL) (n = 3) cases. The
      HCL cases were 100% positive for all but 2 (DBA.44 and CD123) of these markers.
      Annexin A1 showed 100% specificity and accuracy, which was followed by CD123,
      pERK, CD103, HBME-1, CD11c, CD25, CD68, cyclin D1, CD200, T-bet, DBA.44, and
      TRAP, in decreasing order. In conclusion, our results reassured the high
      specificity of annexin A1 and pERK, as well as the diagnostic value of standard
      HCL markers of CD11c, CD25, CD103, and CD123 also in paraffin-embedded BM
      samples. Additional markers, including HBME-1, cyclin D1, CD200, and T-bet also
      represent valuable tools in the differential diagnosis of HCL and its mimics.

PMID- 24903678
TI  - Oxytocin receptor antagonists for inhibiting preterm labour.
AB  - BACKGROUND: Preterm birth, defined as birth between 20 and 36 completed weeks, is
      a major contributor to perinatal morbidity and mortality globally. Oxytocin
      receptor antagonists (ORA), such as atosiban, have been specially developed for
      the treatment of preterm labour. ORA have been proposed as effective tocolytic
      agents for women in preterm labour to prolong pregnancy with fewer side effects
      than other tocolytic agents. OBJECTIVES: To assess the effects on maternal, fetal
      and neonatal outcomes of tocolysis with ORA for women with preterm labour
      compared with placebo or any other tocolytic agent. SEARCH METHODS: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013).
      SELECTION CRITERIA: We included all randomised controlled trials (published and
      unpublished) of ORA for tocolysis of labour between 20 and 36 completed weeks'
      gestation. DATA COLLECTION AND ANALYSIS: Two review authors independently
      evaluated methodological quality and extracted trial data. When required, we
      sought additional data from trial authors. Results are presented as risk ratio
      (RR) for categorical and mean difference (MD) for continuous data with the 95%
      confidence intervals (CI). Where appropriate, the number needed to treat for
      benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated.
      MAIN RESULTS: This review update includes eight additional studies (790 women),
      giving a total of 14 studies involving 2485 women.Four studies (854 women)
      compared ORA (three used atosiban and one barusiban) with placebo. Three studies
      were considered at low risk of bias in general (blinded allocation to treatment
      and intervention), the fourth study did not adequately blind the intervention. No
      difference was shown in birth less than 48 hours after trial entry (average RR
      1.05, 95% CI 0.15 to 7.43; random-effects, (two studies, 152 women), perinatal
      mortality (RR 2.25, 95% CI 0.79 to 6.38; two studies, 729 infants), or major
      neonatal morbidity. ORA (atosiban) resulted in a small reduction in birthweight
      (MD -138.86 g, 95% CI -250.53 to -27.18; two studies with 676 infants). In one
      study, atosiban resulted in an increase in extremely preterm birth (before 28
      weeks' gestation) (RR 3.11, 95% CI 1.02 to 9.51; NNTH 31, 95% CI 8 to 3188) and
      infant deaths (up to 12 months) (RR 6.13, 95% CI 1.38 to 27.13; NNTH 28, 95% CI 6
      to 377). However, this finding may be confounded due to randomisation of more
      women with pregnancy less than 26 weeks' gestation to atosiban. ORA also resulted
      in an increase in maternal adverse drug reactions requiring cessation of
      treatment in comparison with placebo (RR 4.02, 95% CI 2.05 to 7.85; NNTH 12, 95%
      CI 5 to 33). No differences were shown in preterm birth less than 37 weeks'
      gestation or any other adverse neonatal outcomes. No differences were evident by
      type of ORA, although data were limited.Eight studies (1402 women) compared ORA
      (atosiban only) with betamimetics; four were considered of low risk of bias
      (blinded allocation to treatment and to intervention). No statistically
      significant difference was shown in birth less than 48 hours after trial entry
      (RR 0.89, 95% CI 0.66 to 1.22; eight studies with 1389 women), very preterm birth
      (RR 1.70, 95% CI 0.89 to 3.23; one study with 145 women), extremely preterm birth
      (RR 0.84, 95% CI 0.37 to 1.92; one study with 244 women) or perinatal mortality
      (RR 0.55, 95% CI 0.21 to 1.48; three studies with 816 infants). One study (80
      women), of unclear methodological quality, showed an increase in the interval
      between trial entry and birth (MD 22.90 days, 95% CI 18.03 to 27.77). No
      difference was shown in any reported measures of major neonatal morbidity
      (although numbers were small). ORA (atosiban) resulted in less maternal adverse
      effects requiring cessation of treatment (RR 0.05, 95% CI 0.02 to 0.11; NNTB 6,
      95% CI 6 to 6; five studies with 1161 women).Two studies including (225 women)
      compared ORA (atosiban) with calcium channel blockers (CCB) (nifedipine only).
      The studies were considered as having high risk of bias as neither study blinded
      the intervention and in one study it was not known if allocation was blinded. No
      difference was shown in birth less than 48 hours after trial entry (average RR
      1.09, 95% CI 0.44 to 2.73, random-effects; two studies, 225 women) and extremely
      preterm birth (RR 2.14, 95% CI 0.20 to 23.11; one study, 145 women). No data were
      available for the outcome of perinatal mortality. One small trial (145 women),
      which did not employ blinding of the intervention, showed an increase in the
      number of preterm births (before 37 weeks' gestation) (RR 1.56, 95% CI 1.13 to
      2.14; NNTH 5, 95% CI 3 to 19), a lower gestational age at birth (MD -1.20 weeks,
      95% CI -2.15 to -0.25) and an increase in admission to neonatal intensive care
      unit (RR 1.70, 95% CI 1.17 to 2.47; NNTH 5, 95% CI 3 to 20). ORA (atosiban)
      resulted in less maternal adverse effects (RR 0.38, 95% CI 0.21 to 0.68; NNTB 6,
      95% CI 5 to 12; two studies, 225 women) but not maternal adverse effects
      requiring cessation of treatment (RR 0.36, 95% CI 0.01 to 8.62; one study, 145
      women). No longer-term outcome data were included. AUTHORS' CONCLUSIONS: This
      review did not demonstrate superiority of ORA (largely atosiban) as a tocolytic
      agent compared with placebo, betamimetics or CCB (largely nifedipine) in terms of
      pregnancy prolongation or neonatal outcomes, although ORA was associated with
      less maternal adverse effects than treatment with the CCB or betamimetics. The
      finding of an increase in infant deaths and more births before completion of 28
      weeks of gestation in one placebo-controlled study warrants caution. However, the
      number of women enrolled at very low gestations was small. Due to limitations of
      small numbers studied and methodological quality, further well-designed
      randomised controlled trials are needed. Further comparisons of ORA versus CCB
      (which has a better side-effect profile than betamimetics) are needed.
      Consideration of further placebo-controlled studies seems warranted. Future
      studies of tocolytic agents should measure all important short- and long-term
      outcomes for women and infants, and costs.

PMID- 24903679
TI  - Cognitive load imposed by knobology may adversely affect learners' perception of
      utility in using ultrasonography to learn physical examination skills, but not
      anatomy.
AB  - Ultrasonography is increasingly used for teaching anatomy and physical
      examination skills but its effect on cognitive load is unknown. This study aimed
      to determine ultrasound's perceived utility for learning, and to investigate the
      effect of cognitive load on its perceived utility. Consenting first-year medical
      students (n = 137) completed ultrasound training that includes a didactic
      component and four ultrasound-guided anatomy and physical examination teaching
      sessions. Learners then completed a survey on comfort with physical examination
      techniques (three items; alpha = 0.77), perceived utility of ultrasound in
      learning (two items; alpha = 0.89), and cognitive load on ultrasound use
      [measured with a validated nine-point scale (10 items; alpha = 0.88)]. Learners
      found ultrasound useful for learning for both anatomy and physical examination
      (mean 4.2 +/- 0.9 and 4.4 +/- 0.8, respectively; where 1 = very useless and 5 =
      very useful). Principal components analysis on the cognitive load survey revealed
      two factors, "image interpretation" and "basic knobology," which accounted for
      60.3% of total variance. Weighted factor scores were not associated with
      perceived utility in learning anatomy (beta = 0.01, P = 0.62 for "image
      interpretation" and beta = -0.04, P = 0.33 for "basic knobology"). However,
      factor score on "knobology" was inversely associated with perceived utility for
      learning physical examination (beta = -0.06; P = 0.03). While a basic
      introduction to ultrasound may suffice for teaching anatomy, more training may be
      required for teaching physical examination. Prior to teaching physical
      examination skills with ultrasonography, we recommend ensuring that learners have
      sufficient knobology skills.

PMID- 24903680
TI  - New exocrine glands in ants: the hypostomal gland and basitarsal gland in the
      genus Melissotarsus (Hymenoptera: Formicidae).
AB  - Fisher and Robertson (Insect Soc 46: 78-83, 1999) discovered the production of
      silk-like secretions emerging from slit-shaped openings along the anterior margin
      of the ventral hypostoma of Melissotarsus ant workers. The current histological
      study describes a hitherto unknown hypostomal gland from which this silk-like
      substance originates. In addition, this study describes a new basitarsal gland in
      the three pairs of legs of Melissotarsus workers. 

PMID- 24903681
TI  - Trail laying during tandem-running recruitment in the ant Temnothorax albipennis.
AB  - Tandem running is a recruitment strategy whereby one ant leads a single naive
      nest mate to a resource. While tandem running progresses towards the goal, the
      leader ant and the follower ant maintain contact mainly by tactile signals. In
      this paper, we investigated whether they also deposit chemical signals on the
      ground during tandem running. We filmed tandem-running ants and analysed the
      position of the gasters of leaders and followers. Our results show that leader
      ants are more likely to press their gasters down to the substrate compared to
      follower ants, single ants and transporter ants. Forward tandem-run leaders
      (those moving towards a new nest site) performed such trail-marking procedures
      three times more often than reverse tandem leaders (those moving towards an old
      nest site). That leader ants marked the trails more often during forward tandem
      runs may suggest that it is more important to maintain the bond with the follower
      ant on forward tandem runs than on reverse tandem runs. Marked trails on the
      ground may serve as a safety line that improves both the efficiency of tandem
      runs and their completion rates. 

PMID- 24903682
TI  - Do the various categories of somatoform disorders differ from each other in
      symptom profile and psychological correlates.
AB  - BACKGROUND: In routine clinical practice, the subcategories of various somatoform
      disorders are rarely used by the primary care physicians and there is lack of
      data to suggest any difference in the clinical manifestations of these
      subcategories. AIM: To compare the symptom profile, anxiety, depression,
      alexithymia, somato-sensory amplification and hypochondriasis of patients with
      persistent somatoform pain disorder with other subtypes of somatoform disorder.
      METHOD: A total of 119 patients diagnosed with somatoform disorders according to
      the International Classification of Diseases-10th Revision (ICD-10) were
      evaluated for prevalence of somatic symptoms, anxiety, depression, alexithymia,
      hypochondriacal worry and somato-sensory amplification. RESULTS: No significant
      differences were found in the prevalence of various somatic complaints between
      those with persistent somatoform pain disorder group and those diagnosed with
      other somatoform disorders. Co-morbid anxiety and depression were seen in two
      thirds of the patients, but again there was no difference in the prevalence of
      the same between the two groups. Similarly, no significant differences were found
      on alexithymia, hypochondriasis and somato-sensory amplification scales between
      the persistent somatoform pain disorder group and the group with other somatoform
      disorders. CONCLUSION: There are no significant differences between the various
      subcategories of somatoform disorders with regard to the prevalence of somatic
      symptoms, anxiety or depression and psychological correlates of alexithymia,
      hypochondriasis and somato-sensory amplification.

PMID- 24903683
TI  - Pathway to care for psychiatric patients in a developing country: Malawi.
AB  - BACKGROUND: Paramedics dominate primary health care in Malawi where native
      healers also play a major role in the provision of health care and psychiatric
      nurses are the backbone of district mental health services. AIM: The aim is to
      improve understanding of prior care-seeking and treatment of new patients seen at
      mental health services in a developing country like Malawi. METHOD: For one
      calendar month, 128 newly referred patients to the mental health services in the
      three psychiatric units in Malawi were interviewed using an encounter form.
      RESULTS: Most of the patients went through a first carer before attending a
      psychiatric unit with only 11.7% going straight to a psychiatric unit. All
      patients who went straight to a psychiatric unit involved the private/Christian
      Health Association of Malawi (CHAM) unit in the northern region of Malawi. About
      22.7% of the patients had a native healer as a first carer. Only 23% of all
      patients seen went through a second carer, with none going through a third carer.
      Over 8% of those who had a paramedic as their first carer had a native healer as
      their second carer. Duration of stay at different carers varied a lot with about
      half (48.2%) of all patients who saw a native healer as the first carer spending
      more than 2 weeks before referral while about 67.0% of those who saw convectional
      health workers spent 3 days or less before referral. CONCLUSION: The pathway to
      care for patients with psychological problems in Malawi is not very much
      different to pathways to care in other developing countries whereby native
      healers and paramedics play a significant role. With the high proportion of
      patients being seen by native healers and the fact that most patients stay longer
      at native healers before referral, there is need for official collaboration and
      training of native healers on mental health.

PMID- 24903684
TI  - Economic recession and suicidal behaviour: Possible mechanisms and ameliorating
      factors.
AB  - BACKGROUND: A growing body of research evidence from countries around the world
      indicates that economic recession is associated with increases in suicide,
      particularly in males of working age. AIMS: To explore contributory and
      ameliorating factors associated with economic recession and suicide and thereby
      stimulate further research in this area and encourage policy makers to consider
      how best to reduce the impact of recession on mental health and suicidal
      behaviour. METHOD: We conducted a selective review of the worldwide literature
      focusing on possible risk factors, mechanisms and preventative strategies for
      suicidal behaviour linked to economic recession. RESULTS: A model of how
      recession might affect suicide rates is presented. A major and often prolonged
      effect of recession is on unemployment and job insecurity. Other important
      effects include those exerted by financial loss, bankruptcy and home
      repossession. It is proposed these factors may lead directly or indirectly to
      mental health problems such as depression, anxiety and binge drinking and then to
      suicidal behaviour. Countries with active labour market programmes and sustained
      welfare spending during recessions have less marked increases in suicide rates
      than those that cut spending on welfare and job-search initiatives for the
      unemployed. Other measures likely to help include targeted interventions for
      unemployed people, membership of social organisations and responsible media
      reporting. Good primary care and mental health services are needed to cope with
      increased demand in times of economic recession but some governments have in fact
      reduced healthcare spending as an austerity measure. CONCLUSION: The research
      evidence linking recession, unemployment and suicide is substantial, but the
      evidence for the other mechanisms we have investigated is much more tentative. We
      describe the limitations of the existing body of research as well as make
      suggestions for future research into the effects of economic recession on
      suicidal behaviour.

PMID- 24903685
TI  - Purinergic signaling mediated by P2X7 receptors controls myelination in sciatic
      nerves.
AB  - Adenosine-5'-triphosphate, the physiological ligand of P2X receptors, is an
      important factor in peripheral nerve development. P2X7 receptor is expressed in
      Schwann cells (SCs), but the specific effects of P2X7 purinergic signaling on
      peripheral nerve development, myelination, and function are largely unknown. In
      this study, sciatic nerves from P2X7 knockout mice were analyzed for altered
      expression of myelin-associated proteins and for alterations in nerve morphology.
      Immunohistochemical analyses revealed that, in the wild-type peripheral nerves,
      the P2X7 receptor was localized mainly in myelinating SCs, with only a few
      immunopositive nonmyelinating SCs. Complete absence of P2X7 receptor protein was
      confirmed in the sciatic nerves of the knockout mice by Western blot and
      immunohistochemistry. Western blot analysis revealed that expression levels of
      the myelin proteins protein zero and myelin-associated glycoprotein are reduced
      in P2X7 knockout nerves. In accordance with the molecular results, transmission
      electron microscopy analyses revealed that P2X7 knockout nerves possess
      significantly more unmyelinated axons, contained in a higher number of Remak
      bundles. The myelinating/nonmyelinating SC ratio was also decreased in knockout
      mice, and we found a significantly increased number of irregular fibers compared
      with control nerves. Nevertheless, the myelin thickness in the knockout was
      unaltered, suggesting a stronger role for P2X7 in determining SC maturation than
      in myelin formation. In conclusion, we present morphological and molecular
      evidence of the importance of P2X7 signaling in peripheral nerve maturation and
      in determining SC commitment to a myelinating phenotype.

PMID- 24903686
TI  - A default Bayesian hypothesis test for mediation.
AB  - In order to quantify the relationship between multiple variables, researchers
      often carry out a mediation analysis. In such an analysis, a mediator (e.g.,
      knowledge of a healthy diet) transmits the effect from an independent variable
      (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g.,
      consumption of fruits and vegetables). Almost all mediation analyses in
      psychology use frequentist estimation and hypothesis-testing techniques. A recent
      exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who
      outlined a Bayesian parameter estimation procedure for mediation analysis. Here
      we complete the Bayesian alternative to frequentist mediation analysis by
      specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow
      approach. We further extend this default Bayesian test by allowing a comparison
      to directional or one-sided alternatives, using Markov chain Monte Carlo
      techniques implemented in JAGS. All Bayesian tests are implemented in the R
      package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014). 

PMID- 24903688
TI  - A method for simultaneously counterbalancing condition order and assignment of
      stimulus materials to conditions.
AB  - Counterbalanced designs are frequently used in the behavioral sciences. Studies
      often counterbalance either the order in which conditions are presented in the
      experiment or the assignment of stimulus materials to conditions. Occasionally,
      researchers need to simultaneously counterbalance both condition order and
      stimulus assignment to conditions. Lewis (1989; Behavior Research Methods,
      Instruments, & Computers 25:414-415, 1993) presented a method for constructing
      Latin squares that fulfill these requirements. The resulting Latin squares
      counterbalance immediate sequential effects, but not remote sequential effects.
      Here, we present a new method for generating Latin squares that simultaneously
      counterbalance both immediate and remote sequential effects and assignment of
      stimuli to conditions. An Appendix is provided to facilitate implementation of
      these Latin square designs. 

PMID- 24903687
TI  - Presentation and response timing accuracy in Adobe Flash and HTML5/JavaScript Web
      experiments.
AB  - Web-based research is becoming ubiquitous in the behavioral sciences, facilitated
      by convenient, readily available participant pools and relatively straightforward
      ways of running experiments: most recently, through the development of the HTML5
      standard. Although in most studies participants give untimed responses, there is
      a growing interest in being able to record response times online. Existing data
      on the accuracy and cross-machine variability of online timing measures are
      limited, and generally they have compared behavioral data gathered on the Web
      with similar data gathered in the lab. For this article, we took a more direct
      approach, examining two ways of running experiments online-Adobe Flash and HTML5
      with CSS3 and JavaScript-across 19 different computer systems. We used specialist
      hardware to measure stimulus display durations and to generate precise response
      times to visual stimuli in order to assess measurement accuracy, examining
      effects of duration, browser, and system-to-system variability (such as across
      different Windows versions), as well as effects of processing power and graphics
      capability. We found that (a) Flash and JavaScript's presentation and response
      time measurement accuracy are similar; (b) within-system variability is generally
      small, even in low-powered machines under high load; (c) the variability of
      measured response times across systems is somewhat larger; and (d) browser type
      and system hardware appear to have relatively small effects on measured response
      times. Modeling of the effects of this technical variability suggests that for
      most within- and between-subjects experiments, Flash and JavaScript can both be
      used to accurately detect differences in response times across conditions.
      Concerns are, however, noted about using some correlational or longitudinal
      designs online. 

PMID- 24903689
TI  - Optimal sample size allocation for Welch's test in one-way heteroscedastic ANOVA.
AB  - The determination of an adequate sample size is a vital aspect in the planning
      stage of research studies. A prudent strategy should incorporate all of the
      critical factors and cost considerations into sample size calculations. This
      study concerns the allocation schemes of group sizes for Welch's test in a one
      way heteroscedastic ANOVA. Optimal allocation approaches are presented for
      minimizing the total cost while maintaining adequate power and for maximizing
      power performance for a fixed cost. The commonly recommended ratio of sample
      sizes is proportional to the ratio of the population standard deviations or the
      ratio of the population standard deviations divided by the square root of the
      ratio of the unit sampling costs. Detailed numerical investigations have shown
      that these usual allocation methods generally do not give the optimal solution.
      The suggested procedures are illustrated using an example of the cost-efficiency
      evaluation in multidisciplinary pain centers. 

PMID- 24903690
TI  - When the test of mediation is more powerful than the test of the total effect.
AB  - Although previous research has studied power in mediation models, the extent to
      which the inclusion of a mediator will increase power has not been investigated.
      To address this deficit, in a first study we compared the analytical power values
      of the mediated effect and the total effect in a single-mediator model, to
      identify the situations in which the inclusion of one mediator increased
      statistical power. The results from this first study indicated that including a
      mediator increased statistical power in small samples with large coefficients and
      in large samples with small coefficients, and when coefficients were nonzero and
      equal across models. Next, we identified conditions under which power was greater
      for the test of the total mediated effect than for the test of the total effect
      in the parallel two-mediator model. These results indicated that including two
      mediators increased power in small samples with large coefficients and in large
      samples with small coefficients, the same pattern of results that had been found
      in the first study. Finally, we assessed the analytical power for a sequential
      (three-path) two-mediator model and compared the power to detect the three-path
      mediated effect to the power to detect both the test of the total effect and the
      test of the mediated effect for the single-mediator model. The results indicated
      that the three-path mediated effect had more power than the mediated effect from
      the single-mediator model and the test of the total effect. Practical
      implications of these results for researchers are then discussed. 

PMID- 24903691
TI  - A new task format for investigating information search and organization in
      multiattribute decisions.
AB  - In research on multiattribute decisions, information is typically preorganized in
      a well-structured manner (e.g., in attributes-by-options matrices). Participants
      can therefore conveniently identify the information needed for the decision
      strategy they are using. However, in everyday decision situations, we often face
      information that is not well-structured; that is, we not only have to search for,
      but we also need to organize the information. This latter aspect--subjective
      information organization--has so far largely been neglected in decision research.
      The few exceptions used crude experimental manipulations, and the assessment of
      subjective organization suffered from laborious methodology and a lack of
      objectiveness. We introduce a new task format to overcome these methodological
      issues, and we provide an organization index (OI) to assess subjective
      organization of information objectively and automatically. The OI makes it
      possible to assess information organization on the same scale as the strategy
      index (SI) typically used for assessing information search behavior. A simulation
      study shows that the OI has a similar distribution as the SI but that the two
      indices are a priori largely independent. In a validation experiment with
      instructed strategy use, we demonstrate the usefulness of the task to trace
      decision processes in multicue inference situations. 

PMID- 24903692
TI  - Occurrence, plausibility, and desirability for 124 Life Events Inventory items.
AB  - Imagination inflation is where imaginative elaboration of possible childhood
      experiences inflates (increases) participants' estimation that these events
      actually occurred, as indicated by pre- to post-manipulation ratings changes.
      This research primarily uses the Life Events Inventory (LEI), listing possible
      experiences that could have happened during childhood (Garry, Manning, Loftus, &
      Sherman, Psychonomic Bulletin & Review, 3, 208-214, 1996). Although imagination
      inflation research has spawned more than 50 investigations, no normative ratings
      exist on individual items contained in the LEI. To address this, we present
      descriptive statistics (mean, median, standard deviation, confidence interval)
      for 124 LEI items on occurrence (how likely is it that this experience happened
      to you), plausibility (how plausible is it that this event could have happened to
      someone), and desirability (how desirable is this experience). Occurrence and
      plausibility showed similar patterns of mean item ratings and were highly
      correlated, whereas desirability was moderately correlated with plausibility and
      unrelated to occurrence. These data should facilitate a more informed selection
      of specific LEI items to use in further research and can assist in clarifying the
      contributions of normative occurrence, plausibility, and desirability to
      imagination inflation effects. 

PMID- 24903693
TI  - Rotation to a partially specified target matrix in exploratory factor analysis in
      practice.
AB  - The purpose of the present study was to explore the influence of the number of
      targets specified on the quality of exploratory factor analysis solutions with a
      complex underlying structure and incomplete substantive measurement theory. We
      extended previous research in this area by (a) exploring this phenomenon in
      situations in which both the common factor model and the targeted pattern matrix
      contained specification errors and (b) comparing the performance of target
      rotation to an easier-to-use default rotation criterion (i.e., geomin) under
      conditions commonly observed in practice. A Monte Carlo study manipulated target
      error, number of targets, model error, overdetermination, communality, and sample
      size. Outcomes included bias (i.e., accuracy) and variability (i.e., stability)
      with regard to the rotated pattern matrix. The effects of target error were
      negligible for both accuracy and stability, whereas small effects were observed
      for the number of targets for both outcomes. Further, target rotation
      outperformed geomin rotation with regard to accuracy but generally performed
      worse than geomin rotation with regard to stability. These findings underscore
      the potential importance (or caution, in the case of stability) of using extant,
      even if incomplete and somewhat inaccurate, substantive measurement theory to
      inform the rotation criterion in a nonmechanical way. 

PMID- 24903694
TI  - An automated approach for measuring infant head orientation in a face-to-face
      interaction.
AB  - Head orientation in face-to-face interactions between mothers and infants is an
      important component of their communicative processes. Manual coding, however, is
      laborious. Obtaining inter-observer reliability is difficult, with disagreements
      mostly being related to the on- and offsets of a limited number of orientation
      categories. We used a motion capture system and developed an automated method for
      the quantitative measurement of infant head orientation in mother--infant face-to
      face-interactions. Automated motion capture systems have the potential to
      objectively document not only the on- and offset of behaviors, but also
      continuous changes. Infants wore a cap with three reflecting markers, and eight
      infrared cameras captured the positions of the markers. Analytic algorithms
      generated continuous three-dimensional descriptions of the infants' head
      movements. We report here on an initial feasibility study of four infants. To
      evaluate the effectiveness of the automated approach, we compared it to standard
      manual categorical coding of six infant head orientations. We found that the
      central reliability issue was disagreement at the boundaries of the coding
      categories identified by continuous automated coding versus manual coding. The
      automated method was both more feasible and more precise in capturing continuous
      small changes. The study provides evidence for the usefulness of automated
      measurement of infant head orientation when infants interact in relational space.

PMID- 24903695
TI  - Four types of manipulability ratings and naming latencies for a set of 560
      photographs of objects.
AB  - The role of objects' motor affordances in cognition is a topic that has gained in
      popularity over the last decades. However, few studies exist that have normed the
      different motor dimensions of the objects; this limits researchers regarding
      usable stimuli, as well as comparability between studies. In the present study,
      we normed a set of 560 objects on four motor dimensions: the ease with which they
      can be grasped, moved, and pantomimed and the number of actions they afford. We
      then examined whether these four dimensions predict objects' naming latency. We
      believe that these norms will allow researchers interested in the role of motor
      affordances to have a better control over the dimensions they want to manipulate.

PMID- 24903697
TI  - Frontiers in neurodegeneration--new insights and prospects--20th HUPO BPP
      Workshop: 15 September 2013, Yokohama, Japan.
AB  - The HUPO Brain Proteome Project (HUPO BPP) held its 20th workshop in Yokohama,
      Japan, September 15, 2013. The focus of the autumn workshop was on new insights
      and prospects of neurodegenerative diseases.

PMID- 24903701
TI  - Coronary atherosclerosis: the predictor of cardiovascular events.

PMID- 24903702
TI  - Self-assembled bionanoparticles based on the Sulfolobus tengchongensis spindle
      shaped virus 1 (STSV1) coat protein as a prospective bioscaffold for
      nanotechnological applications.
AB  - Biomolecule-nanoparticle hybrid bioconjugates based on bioscaffolds such as
      protein cages and virus capsules have been widely studied. Highly stable and
      durable biotemplates are a vital pillar in constructing bio-inorganic functional
      hybrid composites. Here, we introduce a highly heat-resistant coat protein (CP)
      of Sulfolobus tengchongensis spindle-shaped virus 1 (STSV1) isolated from the
      hyperthermophilic archaeon as a prospective biological matrix. Our experiments
      showed that STSV1 CP was successfully cloned and solubly expressed in the
      Escherichia coli Rosetta-(DE3) host strain. Protein expression was verified by
      SDS-PAGE and western blot analysis of the reference C-terminally six-histidine
      (His6) tagged STSV1 CP (HT-CP). Thermal stability experiments showed that the
      STSV1 coat protein remained fairly stable at 80  degrees C. The proteins can be
      purified facilely by heat treatment followed by size exclusion chromatography
      (SEC). Transmission electron microscopy (TEM) analysis of the purified STSV1 CP
      protein aggregates demonstrated that the protein could self-assemble into
      rotavirus-like nanostructures devoid of genetic materials under our experimental
      conditions. Similar results were obtained for the HT-CP purified by heat
      treatment followed by Ni-NTA and SEC, indicating that moderately engineered STSV1
      CP can retain its self-assembly property. In addition, the STSV1 CP has a high
      binding affinity for TiO2 nanoparticles. This illustrates that the STSV1 CP can
      be used as a bioscaffold in nanobiotechnological applications.

PMID- 24903704
TI  - Effects of licochalcone A on the bioavailability and pharmacokinetics of
      nifedipine in rats: possible role of intestinal CYP3A4 and P-gp inhibition by
      licochalcone A.
AB  - The purpose of this study was to investigate the possible effects of licochalcone
      A (a herbal medicine) on the pharmacokinetics of nifedipine and its main
      metabolite, dehydronifedipine, in rats. The pharmacokinetic parameters of
      nifedipine and/or dehydronifedipine were determined after oral and intravenous
      administration of nifedipine to rats in the absence (control) and presence of
      licochalcone A (0.4, 2.0 and 10 mg/kg). The effect of licochalcone A on P
      glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was also evaluated.
      Nifedipine was mainly metabolized by CYP3A4. Licochalcone A inhibited CYP3A4
      enzyme activity in a concentration-dependent manner with a 50% inhibition
      concentration (IC50 ) of 5.9 MUm. In addition, licochalcone A significantly
      enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells
      overexpressing P-gp. The area under the plasma concentration-time curve from time
      0 to infinity (AUC) and the peak plasma concentration (Cmax ) of oral nifedipine
      were significantly greater and higher, respectively, with licochalcone A. The
      metabolite (dehydronifedipine)-parent AUC ratio (MR) in the presence of
      licochalcone A was significantly smaller compared with the control group. The
      above data could be due to an inhibition of intestinal CYP3A4 and P-gp by
      licochalcone A. The AUCs of intravenous nifedipine were comparable without and
      with licochalcone A, suggesting that inhibition of hepatic CYP3A4 and P-gp was
      almost negligible.

PMID- 24903703
TI  - Geochemistry and microbial ecology in alkaline hot springs of Ambitle Island,
      Papua New Guinea.
AB  - The availability of microbiological and geochemical data from island-based and
      high-arsenic hydrothermal systems is limited. Here, the microbial diversity in
      island-based hot springs on Ambitle Island (Papua New Guinea) was investigated
      using culture-dependent and -independent methods. Waramung and Kapkai are
      alkaline springs high in sulfide and arsenic, related hydrologically to
      previously described hydrothermal vents in nearby Tutum Bay. Enrichments were
      carried out at 24 conditions with varying temperature (45, 80  degrees C), pH
      (6.5, 8.5), terminal electron acceptors (O2, SO4 (2-), S(0), NO3 (-)), and
      electron donors (organic carbon, H2, As(III)). Growth was observed in 20 of 72
      tubes, with media targeting heterotrophic metabolisms the most successful. 16S
      ribosomal RNA gene surveys of environmental samples revealed representatives in
      15 bacterial phyla and 8 archaeal orders. While the Kapkai 4 bacterial clone
      library is primarily made up of Thermodesulfobacteria (74%), no bacterial taxon
      represents a majority in the Kapkai 3 and Waramung samples (40% Proteobacteria
      and 39% Aquificae, respectively). Deinococcus/Thermus and Thermotogae are
      observed in all samples. The Thermococcales dominate the archaeal clone libraries
      (65-85%). Thermoproteales, Desulfurococcales, and uncultured Eury- and
      Crenarchaeota make up the remaining archaeal taxonomic diversity. The culturing
      and phylogenetic results are consistent with the geochemistry of the alkaline,
      saline, and sulfide-rich fluids. When compared to other alkaline, island-based,
      high-arsenic, or shallow-sea hydrothermal communities, the Ambitle Island
      archaeal communities are unique in geochemical conditions, and in taxonomic
      diversity, richness, and evenness.

PMID- 24903705
TI  - Continuous polymer nanocoating on silica nanoparticles.
AB  - Continuous polymer coating of nanoparticles is of interest in many industries
      such as pharmaceuticals, cosmetics, food, and electronics. Here we introduce a
      polymer coating/precipitation technique to achieve a uniform and controllable
      nanosize polymer coating on nanoparticles in a continuous manner. The utility of
      this technique is demonstrated by coating Aerosil silica nanoparticles (SNPs) of
      diameter 12 nm with the polymer Eudragit RL 100. Both hydrophilic and hydrophobic
      SNPs were successfully coated. After determining the cloud point of an acetone
      solution of the polymer containing a controlled amount of the nonsolvent water,
      the solid hollow fiber cooling crystallization (SHFCC) technique was employed to
      continuously coat SNPs with the polymer. A suspension of the SNPs in an acetone
      water solution of the polymer containing a surfactant was pumped through the
      lumen of solid polypropylene hollow fibers in a SHFCC device; cold liquid was
      circulated on the shell side. Because of rapid cooling-induced supersaturation
      and heterogeneous nucleation, precipitated polymers will coat the nanoparticles.
      The thickness and morphology of the nanocoating and the particle size
      distribution of the coated SNPs were analyzed by scanning transmission electron
      microscopy (STEM) with electron energy loss spectroscopy (EELS),
      thermogravimetric analysis (TGA), and dynamic light scattering (DLS). Results
      indicate that uniformly polymer-coated SNPs can be obtained from the SHFCC device
      after suitable post-treatments. The technique is also easily scalable by
      increasing the number of hollow fibers in the SHFCC device. 

PMID- 24903706
TI  - Local interaction strategies and capacity for better care in nursing homes: a
      multiple case study.
AB  - BACKGROUND: To describe relationship patterns and management practices in nursing
      homes (NHs) that facilitate or pose barriers to better outcomes for residents and
      staff. METHODS: We conducted comparative, multiple-case studies in selected NHs
      (N = 4). Data were collected over six months from managers and staff (N = 406),
      using direct observations, interviews, and document reviews. Manifest content
      analysis was used to identify and explore patterns within and between cases.
      RESULTS: Participants described interaction strategies that they explained could
      either degrade or enhance their capacity to achieve better outcomes for
      residents; people in all job categories used these 'local interaction
      strategies'. We categorized these two sets of local interaction strategies as the
      'common pattern' and the 'positive pattern' and summarize the results in two
      models of local interaction. CONCLUSIONS: The findings suggest the hypothesis
      that when staff members in NHs use the set of positive local interaction
      strategies, they promote inter-connections, information exchange, and diversity
      of cognitive schema in problem solving that, in turn, create the capacity for
      delivering better resident care. We propose that these positive local interaction
      strategies are a critical driver of care quality in NHs. Our hypothesis implies
      that, while staffing levels and skill mix are important factors for care quality,
      improvement would be difficult to achieve if staff members are not engaged with
      each other in these ways.

PMID- 24903707
TI  - Usefulness of a lead shielding device for reducing the radiation dose to tissues
      outside the primary beams during CT.
AB  - PURPOSE: This study was done to investigate the efficacy of a lead shield in
      protecting the tissues outside the primary beams, such as the breast and thyroid,
      by measurement of the entrance skin dose during CT of the brain, neck, abdomen,
      and lumbar spine. MATERIALS AND METHODS: Institutional Review Board approval was
      obtained. This study included 150 patients (male:female 25:125, age range 15-45
      years). In females, brain, lumbar spine, and abdominal CT scans, pre-/post
      contrast neck CT scans, and post-contrast liver dynamic CT scans were performed.
      In males, brain CT scans only were performed. Breast shielding was performed in
      all females, and thyroid shielding was conducted in patients with brain CT.
      During all CT studies, the left breast or left thyroid was shielded using a lead
      shield, and the contralateral side was left unshielded. Thus, each breast or
      thyroid measurement had its own control for the same demographic data. The
      efficacy of the shielding of both breasts and thyroids during CT was assessed.
      RESULTS: During brain, abdominal, lumbar, pre-/post-contrast neck, and post
      contrast liver dynamic CT, 33.5, 26.0, 17.4, 26.5, and 16.2 % of the breast skin
      dose were reduced, respectively. During brain CT, the thyroid skin dose was
      reduced by 17.9 % (females) and 20.6 % (males). There were statistically
      significant differences in the skin doses of shielded organs (p < 0.05). Breast
      shielding during neck and liver dynamic CT was the most effective compared with
      breast or thyroid shielding during other CT scans. CONCLUSIONS: We recommend
      breast shielding during neck and liver dynamic CT in young female patients to
      avoid unnecessary radiation exposure.

PMID- 24903708
TI  - Low-dose radiation protocol using 3D mode in a BGO PET/CT.
AB  - BACKGROUND: The use of positron emission tomography combined with computed
      tomography (PET/CT) has brought about significant technological advancement in
      diagnostic imaging, and a number of PET/CT scanners with bismuth germanate
      detectors can perform imaging in both 2D and 3D acquisition modes. Nevertheless,
      certain image acquisition parameters and physical features of patients have to be
      considered when designing low-dose protocols in the 3D mode. PURPOSE: The aim of
      this study was to compare images acquired in 2D and 3D modes and establish a low
      dose protocol for use in PET/CT imaging, decreasing patient exposure to radiation
      without compromising results. METHODS: A total of 30 patients, aged 4-72 years,
      participated in this prospective study, which was conducted at Albert Einstein
      Hospital, Sao Paulo, Brazil. Images were evaluated for picture quality,
      presence/absence of lesions and the number of lesions that were detectable in
      both acquisition modes. RESULTS: The results consistently showed that the loss in
      image quality in the 3D mode did not affect exam interpretation and lesion
      detection when compared with 2D at higher dose and for a longer time.
      CONCLUSIONS: We therefore conclude that administration of 3.7 MBq [(18)F]
      fluorodeoxyglucose (FDG)/kg for an acquisition time of 3 min per FOV (field of
      view) is optimal for image acquisition in the 3D mode. This protocol, which
      reduces the acquisition time and radiation dose, is quite beneficial, especially
      for children.

PMID- 24903711
TI  - The donor-stabilized silylene bis[N,N'-diisopropylbenzamidinato(-)]silicon(II):
      synthesis, electronic structure, and reactivity.
AB  - A convenient and robust synthesis of bis[N,N'-diisopropylbenzamidinato(
      )]silicon(II) (1), a donor-stabilized silylene, has been developed (35 g scale).
      To get further information about the reactivity profile of 1, a series of
      oxidative addition reactions were studied. Treatment of 1 with PhSe-SePh (Se-Se
      bond activation), C6F6 (C-F activation), and CO2 (C=O activation/cycloaddition)
      yielded the neutral six-coordinate silicon(IV) complexes 10, 11, and 13,
      respectively. Treatment of 1 with N2O resulted in the formation of the dinuclear
      five-coordinate silicon(IV) complex 12 (oxidative addition/dimerization), which
      contains a four-membered Si2O2 ring. Compounds 10-13 were characterized by NMR
      spectroscopic studies in the solid state and in solution and by crystal structure
      analyses. Silylene 1 is three-coordinate in the solid state (from crystal
      structure analysis) and exists as the four-coordinate isomer 1' in benzene
      solution (from computational studies). Based on state-of-the-art relativistic DFT
      analyses, the four-coordinate species 1' was demonstrated to be the
      thermodynamically favored isomer in benzene solution (favored by DeltaG = 6.6
      kcal mol(-1) over the three-coordinate species 1). The reason for this was
      studied by bonding analyses of 1 and 1'. Furthermore, the (29)Si NMR chemical
      shifts of 1 and 1' were computed, and in the case of 1' it was analyzed how this
      NMR spectroscopic parameter is affected by solvation. These studies further
      supported the assumption that the silylene is four-coordinate in solution.

PMID- 24903709
TI  - Tuning multiple imputation by predictive mean matching and local residual draws.
AB  - BACKGROUND: Multiple imputation is a commonly used method for handling incomplete
      covariates as it can provide valid inference when data are missing at random.
      This depends on being able to correctly specify the parametric model used to
      impute missing values, which may be difficult in many realistic settings.
      Imputation by predictive mean matching (PMM) borrows an observed value from a
      donor with a similar predictive mean; imputation by local residual draws (LRD)
      instead borrows the donor's residual. Both methods relax some assumptions of
      parametric imputation, promising greater robustness when the imputation model is
      misspecified. METHODS: We review development of PMM and LRD and outline the
      various forms available, and aim to clarify some choices about how and when they
      should be used. We compare performance to fully parametric imputation in
      simulation studies, first when the imputation model is correctly specified and
      then when it is misspecified. RESULTS: In using PMM or LRD we strongly caution
      against using a single donor, the default value in some implementations, and
      instead advocate sampling from a pool of around 10 donors. We also clarify which
      matching metric is best. Among the current MI software there are several poor
      implementations. CONCLUSIONS: PMM and LRD may have a role for imputing covariates
      (i) which are not strongly associated with outcome, and (ii) when the imputation
      model is thought to be slightly but not grossly misspecified. Researchers should
      spend efforts on specifying the imputation model correctly, rather than expecting
      predictive mean matching or local residual draws to do the work.

PMID- 24903710
TI  - Anopheles ziemanni a locally important malaria vector in Ndop health district,
      north west region of Cameroon.
AB  - BACKGROUND: Malaria transmission in Cameroon is mediated by a plethora of vectors
      that are heterogeneously distributed across the country depending on the biotope.
      To effectively guide malaria control operations, regular update on the role of
      local Anopheles species is essential. Therefore, an entomological survey was
      conducted between August 2010 and May 2011 to evaluate the role of the local
      anopheline population in malaria transmission in three villages of the Ndop
      health district in the northwest region of Cameroon where malaria is holoendemic,
      as a means to acquiring evidence based data for improved vector intervention.
      METHODS: Mosquitoes were sampled both indoor and outdoor for four consecutive
      nights in each locality during each month of survey. Sampling was done by the
      human landing catch method on volunteers. Anopheles species were identified
      morphologically and their ovaries randomly dissected for parity determination.
      Infection with Plasmodium falciparum was detected by Circumsporozoite protein
      ELISA. Members of An. gambiae complex were further identified to molecular level
      by PCR and RFLP PCR. RESULTS: An. ziemanni was the main malaria vector and
      whether outdoor or indoor. The man biting rate for the vectors ranged from 6.75
      to 8.29 bites per person per night (b/p/n). The entomological inoculation rate
      for this vector species was 0.0278 infectious bites per person per night (ib/p/n)
      in Mbapishi, 0.034 ib/p/n in Mbafuh, and 0.063 ib/p/n in Backyit. These were by
      far greater than that for An. gambiae. No difference was observed in the parity
      rate of these two vectors. PCR analysis revealed the presence of only An.
      colluzzi (M- form). CONCLUSIONS: An. ziemanni is an important local malaria
      vector in Ndop health district. The findings provide useful baseline information
      on the anopheles species composition, their distribution and role in malaria
      transmission that would guide the implementation of integrated vector management
      strategies in the locality.

PMID- 24903712
TI  - Solid-State (29)Si NMR and neutron-diffraction studies of Sr(0.7)K(0.3)SiO(2.85)
      oxide ion conductors.
AB  - K/Na-doped SrSiO3-based oxide ion conductors were recently reported as promising
      candidates for low-temperature solid-oxide fuel cells. Sr0.7K0.3SiO2.85, close to
      the solid-solution limit of Sr1-xKxSiO3-0.5x, was characterized by solid-state
      (29)Si NMR spectroscopy and neutron powder diffraction (NPD). Differing with the
      average structure containing the vacancies stabilized within the isolated Si3O9
      tetrahedral rings derived from the NPD study, the (29)Si NMR data provides new
      insight into the local defect structure in Sr0.7K0.3SiO2.85. The Q(1)-linked
      tetrahedral Si signal in the (29)Si NMR data suggests that the Si3O9 tetrahedral
      rings in the K-doped SrSiO3 materials were broken, forming Si3O8 chains. The
      Si3O8 chains can be stabilized by either bonding with the oxygen atoms of the
      absorbed lattice water molecules, leading to the Q(1)-linked tetrahedral Si, or
      sharing oxygen atoms with neighboring Si3O9 units, which is consistent with the
      Q(3)-linked tetrahedral Si signal detected in the (29)Si NMR spectra. 

PMID- 24903714
TI  - An electrohydrodynamic bioprinter for alginate hydrogels containing living cells.
AB  - In this work we present a bioprinting technique that exploits the
      electrohydrodynamic process to obtain a jet of liquid alginate beads containing
      cells. A printer is used to microfabricate hydrogels block by block following a
      bottom-up approach. Alginate beads constitute the building blocks of the
      microfabricated structures. The beads are placed at predefined position on a
      target substrate made of calcium-enriched gelatin, where they crosslink upon
      contact without the need of further postprocessing. The printed sample can be
      easily removed from the substrate at physiological temperature. Three-dimensional
      printing is accomplished by the deposition of multiple layers of hydrogel. We
      have investigated the parameters influencing the process, the compatibility of
      the printing procedure with cells, and their survival after printing. 

PMID- 24903715
TI  - Revisiting the Asset Model: a clarification of ideas and terms.

PMID- 24903717
TI  - Revoyons le modele fonde sur les atouts en clarifiant les idees et la
      terminologie.

PMID- 24903713
TI  - Intracellular Abeta pathology and early cognitive impairments in a transgenic rat
      overexpressing human amyloid precursor protein: a multidimensional study.
AB  - Numerous studies have implicated the abnormal accumulation of intraneuronal
      amyloid-beta (Abeta) as an important contributor to Alzheimer's disease (AD)
      pathology, capable of triggering neuroinflammation, tau hyperphosphorylation and
      cognitive deficits. However, the occurrence and pathological relevance of
      intracellular Abeta remain a matter of controversial debate. In this study, we
      have used a multidimensional approach including high-magnification and super
      resolution microscopy, cerebro-spinal fluid (CSF) mass spectrometry analysis and
      ELISA to investigate the Abeta pathology and its associated cognitive
      impairments, in a novel transgenic rat model overexpressing human APP. Our
      microscopy studies with quantitative co-localization analysis revealed the
      presence of intraneuronal Abeta in transgenic rats, with an immunological signal
      that was clearly distinguished from that of the amyloid precursor protein (APP)
      and its C-terminal fragments (CTFs). The early intraneuronal pathology was
      accompanied by a significant elevation of soluble Abeta42 peptides that
      paralleled the presence and progression of early cognitive deficits, several
      months prior to amyloid plaque deposition. Abeta38, Abeta39, Abeta40 and Abeta42
      peptides were detected in the rat CSF by MALDI-MS analysis even at the plaque
      free stages; suggesting that a combination of intracellular and soluble
      extracellular Abeta may be responsible for impairing cognition at early time
      points. Taken together, our results demonstrate that the intraneuronal
      development of AD-like amyloid pathology includes a mixture of molecular species
      (Abeta, APP and CTFs) of which a considerable component is Abeta; and that the
      early presence of these species within neurons has deleterious effects in the
      CNS, even before the development of full-blown AD-like pathology.

PMID- 24903719
TI  - Revisar el Modelo de los Activos: aclaracion de ideas y terminos.

PMID- 24903721
TI  - Isolated renal zygomycosis in an immunocompetent patient.
AB  - Zygomycosis is a rare opportunistic fungal infection in immunocompetent patients.
      Isolated renal involvement by zygomycosis is extremely rare and diagnosed mainly
      during postmortem study. We report a case of a 22-year-old man with right upper
      quadrant pain and fever. The CT of the abdomen revealed renal cell carcinoma and
      subsequent nephrectomy was performed. The histopathological diagnosis of
      nephrectomy established zygomycosis. After that patient was given 2 months
      antifungal therapy and is living well even after her 1 year follow-up.

PMID- 24903722
TI  - Urachal cancer with direct caecal invasion: differential diagnosis from primary
      colon cancer.
AB  - A 56-year-old man who had a history of repeated previous treatment for cystitis
      was admitted with abdominal distension, dysuria, pollakiuria, nocturia and
      sensation of urine retention after emptying the bladder. A CT scan showed a 10 cm
      irregularly shaped soft tissue mass abutting the anterosuperior aspect of the
      urinary bladder with wall thickening and a soft tissue component in the caecum.
      Colonoscopy revealed an encircling huge fungating mass on the caecum. The tumour
      was removed surgically. Histological examination showed moderately differentiated
      adenocarcinoma extending to the caecal wall and the bladder mucosa, the origin of
      the mass was consistent with that of a urachal cyst. The epicentre of the tumour
      was located in the bladder wall, with a distinct margin as a pathological
      feature. The patient was diagnosed with urachal cancer and concurrent direct
      caecal invasion. 

PMID- 24903723
TI  - Older men with unexplained hepatitis.
AB  - A 59-year-old Caucasian man presented with painless jaundice for 6 weeks. He
      drank 70 units of alcohol per week. Examination revealed jaundice, spider
      angiomata and a 3 cm firm hepatomegaly. Initial bloods: bilirubin 152 umol/L,
      alanine aminotransferase 1484 IU/L, alkaline phosphatase 130 IU/L, gamma-glutamyl
      transpeptidase 1224 IU/L and International Normalised Ratio 1.1. A standard liver
      screen was normal, and an abdominal ultrasound/CT scan suggested cirrhosis,
      confirmed by liver biopsy on day 5. Hepatitis E virus (HEV) serology on day 6
      indicated acute infection. He developed severe hepatic decompensation
      characterised by worsening jaundice, ascites and variceal bleeding. On day 33
      ribavirin 600 mg was initiated though discontinued after 2 weeks on receipt of a
      negative HEV RNA. At the last follow-up he had recovered, and remains abstinent
      from alcohol. We describe a case of autochthonously (locally) acquired HEV
      infection with life-threatening hepatic decompensation in the presence of
      undiagnosed alcohol-related cirrhosis.

PMID- 24903724
TI  - Myristicin and phenytoin toxicity in an infant.
AB  - A developmentally normal infant presented with repeated episodes of afebrile
      status epilepticus following nutmeg ingestion. He had developed two episodes of
      afebrile status epilepticus and had received different treatments earlier, but
      the details of treatment were not available. On admission, he redeveloped
      convulsions and loading doses of phenytoin, phenobarbitone and midazolam were
      administered. However, seizures persisted and extrapyramidal movements, nystagmus
      and visual dysfunction were noted. Iatrogenic phenytoin toxicity was considered
      and confirmed by drug levels. His symptoms completely disappeared after
      discontinuation of phenytoin therapy. The initial seizures were attributed to
      myristicin, an active component of nutmeg, because of the temporal association.
      However, the subsequent seizures were due to phenytoin toxicity caused by
      administration of multiple loading doses. This case highlights that nutmeg, a
      spice, can cause serious toxic effects like status epilepticus. Furthermore,
      treatment of status epilepticus with phenytoin can cause iatrogenic seizures due
      to its narrow therapeutic range. 

PMID- 24903725
TI  - Drug-associated aquagenic wrinkling of the palms in an atopic male patient.

PMID- 24903726
TI  - A midline for oxaliplatin infusion: the myth of safety devices.
AB  - Oxaliplatin is a platinum compound mainly used in the treatment of colorectal
      cancer. According to its manufacturer it is not considered vesicant agent though
      it has been shown to cause severe tissue damage if extravasation occurs in large
      doses. Several cases of extravasation have been reported; most of them from
      incorrectly placed peripheral cannula or incorrect use of central venous access
      devices. To reduce these risks, peripherally inserted central catheters and
      midline catheters have been increasingly used and are especially helpful if poor
      peripheral venous access. Midlines are mainly used for patients not receiving
      vesicant drugs, and are generally inserted without radiological guidance. They
      are believed to be safe, but we present the first ever-documented oxaliplatin
      extravasation injury from a midline catheter. 

PMID- 24903727
TI  - Mediastinitis by Actinomyces meyeri after oesophageal stent placement.
AB  - Actinomyces meyeri is a Gram-positive anaerobic forming bacterium of the genus
      Actinomyces, part of the oral cavity's flora, and its classification remains an
      unresolved issue. It is an extremely rare cause of disease, occurring in middle
      aged immunocompetent patients and frequently misdiagnosed as malignancy or lung
      abscess. A 56-year-old man diagnosed with oesophageal squamous cell carcinoma had
      an endoscopically placed stent to palliate his dysphagia. Two weeks later he
      presented with thoracalgia and fever, interpreted as a common lung infection.
      Owing to lack of improvement, additional examinations were undertaken revealing
      mediastinum involvement. Unlike the good prognosis usually associated with this
      infection, the patient eventually died, reflecting the aggressive nature of his
      underlying condition. To our knowledge, this is the first report of mediastinitis
      by A. meyeri, supporting the described propensity of this agent to disseminate,
      particularly to the thoracic cavity, although probably in this case with an
      iatrogenic contribution. 

PMID- 24903728
TI  - Posterior reversible encephalopathy syndrome resulting from repeat bortezomib
      usage.
AB  - Bortezomib is a chemotherapeutic agent that acts via proteasome inhibition
      resulting in cellular apoptosis and inhibition of angiogenesis. Although widely
      accepted as treatment of multiple myeloma and non-Hodgkin's lymphoma, it has also
      been shown to be efficacious in a variety of solid tumours such as pancreatic and
      colonic. Posterior reversible encephalopathy syndrome (PRES) is a
      neuroradiological syndrome characterised by vasogenic oedema involving the
      postero-occipital cortical and subcortical white matter resulting in visual
      disturbances, seizures and altered mental status. Although in most cases PRES is
      reversible with removal of the provoking condition or drug, if not appropriately
      recognised and treated it may lead to permanent and life-threatening sequelae
      such as intracerebral haemorrhage and ischaemic infarction. We report a case of
      PRES associated with bortezomib therapy and contrast it with four other
      previously reported cases. Recognition of this potentially severe neurological
      complication is important with the increasingly widespread use of bortezomib. 

PMID- 24903729
TI  - Horner's syndrome secondary to intervertebral disc herniation at the level of T1
      2.
AB  - A 54-year-old Caucasian woman presented with a 6 week history of periscapular
      pain and a T1 radiculopathy associated with Horner's syndrome. MRI of her
      cervicothoracic spine revealed an intervertebral disc herniation at the level of
      T1-2. During investigation she experienced some improvement in her symptoms and a
      conservative approach was pursued. At 6 months her pain and radiculopathy had
      resolved, and there was mild residual ptosis. 

PMID- 24903730
TI  - Efficacy of repeated exposure and flavour-flavour learning as mechanisms to
      increase preschooler's vegetable intake and acceptance.
AB  - BACKGROUND: Dutch children's diets, like the diets of many children in Europe and
      the US are not balanced, do not contain enough vegetables and have been
      associated with a high prevalence of childhood obesity. Promoting children's
      vegetable intake is challenging. OBJECTIVE: We investigated the relative
      effectiveness of repeated exposure and flavour-flavour learning in increasing
      vegetable intake and acceptance in preschoolers. METHODS: During an intervention
      period of 7 weeks, 39 toddlers (aged 1.5 to 4 years) consumed red beet and
      parsnip crisps at day-care centres in Wageningen, the Netherlands. Half of the
      group received red beet crisps with a dip of tomato ketchup (Conditioned [C]) and
      parsnip with a neutral white sauce (Unconditioned, [UC]), whereas for the other
      half the order was reversed (red beet [UC], parsnip [C]). Preference and ad
      libitum consumption of vegetable crisps were measured once before and three times
      after the intervention over the course of a 6-month follow-up period to assess
      longer-term effects. RESULTS: Intake increased significantly after the
      intervention for both vegetables (on average with 8 g; an increase of
      approximately 300%), and this effect was persistent even 6 months afterwards. The
      increase was irrespective of crisps being offered with C or UC dip sauce.
      CONCLUSIONS: These results suggest a robust and persistent effect of repeated
      exposure but no effect of flavour-flavour learning. Offering pure vegetable
      tastes repeatedly is sufficient to increase intake.

PMID- 24903731
TI  - Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity.
AB  - Common autoimmune disorders tend to co-exist in the same subjects and cluster in
      families. The objective of this study was to determine the prevalence of
      autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with
      and without thyroid-associated orbitopathy (TAO). This was a cross-sectional
      study conducted at an academic tertiary referral centre. Of 1310 patients with
      AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's
      thyroiditis (HT)] followed at a specialized joint thyroid-eye out-patient clinic,
      176 (13.4%) had an adult type of the autoimmune polyglandular syndrome, 129
      (9.8%) type 1 diabetes, 111 (8.5%) coeliac disease, 60 (4.6%) type A autoimmune
      gastritis, 57 (4.4%) vitiligo and 25 (1.9%) Addison's disease. Coeliac disease
      and autoimmune gastritis were associated positively with GD [odds ratio (OR) =
      2.18; P = 0.002 and OR = 6.52; P < 0.001], whereas type 1 diabetes, Addison's
      disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis
      and Sjogren's syndrome were 'protective' for GD and thus linked to HT, OR = 0.49
      (P < 0.001), 0.06 (P < 0.001), 0.25 (P < 0.001), 0.50 (P = 0.090) and 0.32 (P =
      0.003), respectively. Of 610 (46.6%) AITD patients with TAO, 584 (95.7%) and 26
      (4.3%) had GD and HT, respectively (P < 0.001). TAO was most prevalent in GD
      patients with coeliac disease (94%, OR = 1.87, P < 0.001). Multivariate analysis
      showed high OR for coeliac disease and autoimmune gastritis (3.4 and 4.03, both P
      < 0.001) pertaining to the association with TAO while type 1 diabetes, Addison's
      disease and alopecia areata were protective for TAO. In patients with TAO,
      coeliac disease is the most prevalent co-morbid autoimmune condition and rates
      are increased compared to GD patients without TAO.

PMID- 24903735
TI  - Discovery of novel 17-phenylethylaminegeldanamycin derivatives as potent Hsp90
      inhibitors.
AB  - Twenty-six 17-phenylethylamine-modified geldanamycin derivatives were synthesized
      and evaluated for antiproliferation activity in human cancer cell lines, LNCaP
      and MDA-MB-231. Five derivatives (2j, 2q, 2v, 2x, and 2 y) showed excellent in
      vitro antitumor activities. Among them, compound 2 y was the most potent lead,
      with IC50 values of 0.27 +/- 0.11 and 0.86 +/- 0.23 MUm for LNCaP and MDA-MB-231,
      respectively. In particular, compound 2 y was more active than its precursor
      geldanamycin against LNCap cells. Liver injury test in mice demonstrated that 2 y
      group showed no significant difference for serum alanine aminotransferase (ALT)
      activity versus vehicle control, indicating that 2 y was a promising antitumor
      candidate. Preliminary structure-activity relationship (SAR) and molecular
      dynamics (MD) simulations of this new series of geldanamycin derivatives were
      also investigated, suggesting a theoretical model of 17
      phenylethylaminegeldanamycins binding to Hsp90.

PMID- 24903732
TI  - Imbalance of regulatory T cells and T helper type 17 cells in patients with
      chronic hepatitis C.
AB  - Pegylated interferon and ribavirin combination therapy is known to be effective
      in suppressing viral replication in 50-60% of hepatitis C virus (HCV)-infected
      patients. However, HCV-infected patients often exhibit varied responses to
      therapy. Therefore, the identification of immunological markers associated with
      the clinical outcomes of antiviral treatment is critical for improvement of
      therapeutic options. In this study, we aimed to investigate the ratio of CD4(+)
      CD25(+) FoxP3(+) regulatory T (Treg) cells to interleukin-17A (IL-17A) -producing
      T helper type 17 (Th17) cells, and its association with clinical outcomes in
      response to anti-HCV treatment. In all, 114 patients with HCV infection received
      pegylated interferon-alpha2a and ribavirin therapy for 48 weeks, and the
      frequency of Treg cells and Th17 cells as well as the levels of secreted
      cytokines were longitudinally analysed by flow cytometry and ELISA. Treg cell
      proportions and IL-10 production were significantly elevated in HCV-infected
      patients, especially for HCV genotype 1b. However, the frequency of Th17 cells as
      well as the secretion of IL-17, IL-22 and IL-23 did not reveal notable difference
      between HCV infections and healthy individuals. Inhibition of HCV replication was
      accompanied by a reduction in Treg cells, but little influence on Th17 cells,
      which led to a significant decrease in Treg : Th17 ratios. Skewed Treg : Th17
      ratios existed in chronic hepatitis C. HCV RNA load is closely associated with
      Treg : Th17 ratios during pegylated interferon-alpha2a and ribavirin treatment in
      HCV-infected patients. The imbalance of Treg cells to Th17 cells might play an
      important role in persistent HCV infection.

PMID- 24903736
TI  - Modeling larval malaria vector habitat locations using landscape features and
      cumulative precipitation measures.
AB  - BACKGROUND: Predictive models of malaria vector larval habitat locations may
      provide a basis for understanding the spatial determinants of malaria
      transmission. METHODS: We used four landscape variables (topographic wetness
      index [TWI], soil type, land use-land cover, and distance to stream) and
      accumulated precipitation to model larval habitat locations in a region of
      western Kenya through two methods: logistic regression and random forest.
      Additionally, we used two separate data sets to account for variation in habitat
      locations across space and over time. RESULTS: Larval habitats were more likely
      to be present in locations with a lower slope to contributing area ratio (i.e.
      TWI), closer to streams, with agricultural land use relative to nonagricultural
      land use, and in friable clay/sandy clay loam soil and firm, silty clay/clay soil
      relative to friable clay soil. The probability of larval habitat presence
      increased with increasing accumulated precipitation. The random forest models
      were more accurate than the logistic regression models, especially when
      accumulated precipitation was included to account for seasonal differences in
      precipitation. The most accurate models for the two data sets had area under the
      curve (AUC) values of 0.864 and 0.871, respectively. TWI, distance to the nearest
      stream, and precipitation had the greatest mean decrease in Gini impurity
      criteria in these models. CONCLUSIONS: This study demonstrates the usefulness of
      random forest models for larval malaria vector habitat modeling. TWI and distance
      to the nearest stream were the two most important landscape variables in these
      models. Including accumulated precipitation in our models improved the accuracy
      of larval habitat location predictions by accounting for seasonal variation in
      the precipitation. Finally, the sampling strategy employed here for model
      parameterization could serve as a framework for creating predictive larval
      habitat models to assist in larval control efforts.

PMID- 24903738
TI  - Massive renal size is not a contraindication to a laparoscopic approach for
      bilateral native nephrectomies in autosomal dominant polycystic kidney disease
      (ADPKD).
AB  - OBJECTIVE: To determine if massive renal size should be a contraindication for
      attempting a laparoscopic approach to bilateral native nephrectomies in patients
      with autosomal dominant polycystic kidney disease (ADPKD). PATIENTS AND METHODS:
      We retrospectively reviewed all laparoscopic bilateral nephrectomies performed
      for ADPKD at our institution from 1 January 2000 to 31 December 2012. We
      stratified patients by kidney weight (with or without at least one kidney
      weighing >2500 g) and compared perioperative data, complications, and status of
      kidney allografts. Additionally, the subset of patients with at least one kidney
      weighing >3500 g was compared with the rest of the cohort. RESULTS: We identified
      68 patients; mean (range) individual kidney weight was 1984 (197-5042) g. In all,
      24 patients had at least one kidney weighing >2500 g, yet patients in this group
      were not significantly different from the rest of the cohort for complications,
      estimated blood loss, transfusion rate, or duration of hospitalisation. For those
      who underwent simultaneous renal allotransplantation, native kidney size was not
      associated with graft outcomes. Additionally, of the six patients with at least
      one kidney weighing >3500 g, only one required a blood transfusion, and the group
      had no intraoperative or postoperative Clavien grade >=3 complications. None of
      the cohort required conversion to open surgery. CONCLUSION: Massive size of
      polycystic kidneys is not a contraindication to attempting a laparoscopic
      approach to bilateral nephrectomies in an experienced, high-volume centre.

PMID- 24903739
TI  - External validation of the estimated posttransplant survival score for allocation
      of deceased donor kidneys in the United States.
AB  - The US kidney allocation system adopted in 2013 will allocate the best 20% of
      deceased donor kidneys (based on the kidney donor risk index [KDRI]) to the 20%
      of waitlisted patients with the highest estimated posttransplant survival (EPTS).
      The EPTS has not been externally validated, raising concerns as to its
      suitability to discriminate between kidney transplant candidates. We examined
      EPTS using data from the Australia and New Zealand Dialysis and Transplant
      (ANZDATA) Registry. We included 4983 adult kidney-only deceased donor transplants
      over 2000-2011. We constructed three Cox models for patient survival: (i) EPTS
      alone; (ii) EPTS plus donor age, hypertension and HLA-DR mismatch; and (iii) EPTS
      plus log(KDRI). All models demonstrated moderately good discrimination, with
      Harrell's C statistics of 0.67, 0.68 and 0.69, respectively. These results are
      virtually identical to the internal validation that demonstrated a c-statistic of
      0.69. These results provide external validation of the EPTS as a moderately good
      tool for discriminating posttransplant survival of adult kidney-only transplant
      recipients. 

PMID- 24903737
TI  - First-year results of the Global Influenza Hospital Surveillance Network: 2012
      2013 Northern hemisphere influenza season.
AB  - BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) was
      developed to improve understanding of severe influenza infection, as represented
      by hospitalized cases. The GIHSN is composed of coordinating sites, mainly
      affiliated with health authorities, each of which supervises and compiles data
      from one to seven hospitals. This report describes the distribution of influenza
      viruses A(H1N1), A(H3N2), B/Victoria, and B/Yamagata resulting in hospitalization
      during 2012-2013, the network's first year. METHODS: In 2012-2013, the GIHSN
      included 21 hospitals (five in Spain, five in France, four in the Russian
      Federation, and seven in Turkey). All hospitals used a reference protocol and
      core questionnaire to collect data, and data were consolidated at five
      coordinating sites. Influenza infection was confirmed by reverse-transcription
      polymerase chain reaction. Hospitalized patients admitted within 7 days of onset
      of influenza-like illness were included in the analysis. RESULTS: Of 5034
      patients included with polymerase chain reaction results, 1545 (30.7%) were
      positive for influenza. Influenza A(H1N1), A(H3N2), and both B lineages co
      circulated, although distributions varied greatly between coordinating sites and
      over time. All age groups were affected. A(H1N1) was the most common influenza
      strain isolated among hospitalized adults 18-64 years of age at four of five
      coordinating sites, whereas A(H3N2) and B viruses were isolated more often than
      A(H1N1) in adults >=65 years of age at all five coordinating sites. A total of 16
      deaths and 20 intensive care unit admissions were recorded among patients with
      influenza. CONCLUSIONS: Influenza strains resulting in hospitalization varied
      greatly between coordinating sites and over time. These first-year results of the
      GIHSN are relevant, useful, and timely. Due to its broad regional
      representativeness and sustainable framework, this growing network should
      contribute substantially to understanding the epidemiology of influenza,
      particularly for more severe disease.

PMID- 24903740
TI  - Emergency medical equipment on board German airliners.
AB  - BACKGROUND: Medical emergencies often occur on commercial airline flights, but
      valid data on their causes and consequences are rare. Therefore, it is unclear
      what emergency medical equipment is necessary. Although a minimum standard for
      medical equipment is defined in regulations, additional material is not
      standardized and may vary significantly between different airlines. METHODS:
      German airlines operating aircrafts with more than 30 seats were selected and
      interviewed with a 5-page written questionnaire between August 2011 and January
      2012. Besides pre-packed and required emergency medical material, drugs, medical
      devices, and equipment lists were queried. If no reply was received, airlines
      were contacted another three times by e-mail and/or phone. Descriptive analysis
      was used for data presentation and interpretation. RESULT: From a total of 73
      German airlines, 58 were excluded from analysis (eg, those not providing
      passenger transport). Fifteen airlines were contacted and data of 13 airlines
      were available for analysis (two airlines did not participate). A first aid kit
      was available on all airlines. Seven airlines reported having a doctor's kit, and
      another four provided an "emergency medical kit." Four airlines provided an
      automated external defibrillator (AED)/electrocardiogram (ECG). While six
      airlines reported providing anesthesia drugs, a laryngoscope, and endotracheal
      tubes, another four airlines did not provide even a resuscitator bag. One airline
      did not provide any material for cardiopulmonary resuscitation (CPR).
      CONCLUSIONS: Although the minimal material required according to European
      aviation regulations is provided by all airlines for medical emergencies, there
      are significant differences in the provision of additional material. The
      equipment on most airlines is not sufficient for the treatment of specific
      emergencies according to published medical guidelines (eg, for CPR or acute
      myocardial infarction).

PMID- 24903741
TI  - Intrauterine blood transfusion: current indications and associated risks.
AB  - Fetal anemia is a serious complication in pregnancy and associated with perinatal
      mortality and morbidity. During 25 years of worldwide experience with
      intravascular intrauterine blood transfusion, a variety of indications have been
      described. Intrauterine transfusion (IUT) treatment is considered most successful
      for fetal anemia due to red cell alloimmunization. Moreover, the use of this
      procedure has also been reported in pregnancies with parvovirus B19 infection,
      fetomaternal hemorrhage and placental chorioangiomas, for example. This review
      focuses on the current indications of intrauterine blood transfusions. In
      addition, we describe the potential complications of IUT treatment.

PMID- 24903742
TI  - Brainstem auditory evoked responses in an equine patient population. Part II:
      foals.
AB  - BACKGROUND: Reports of the use of brainstem auditory evoked response (BAER) as a
      diagnostic modality in foals have been limited. HYPOTHESIS/OBJECTIVES: To
      describe BAER findings and associated causes of hearing loss in foals. ANIMALS:
      Study group 18 foals (15 neonatal, 3 nonneonatal), control group (5 neonatal
      foals). METHODS: Retrospective. BAER records from the Clinical Neurophysiology
      Laboratory were reviewed from the years of 1982 to 2013. Peak latencies,
      amplitudes, and interpeak intervals were measured when visible. Clinical data
      were extracted from the medical records. Foals were grouped under disease
      categories. Descriptive statistics were performed. RESULTS: Ten neonatal foals
      had complete absence of BAER bilaterally and 5 had findings within reference
      range. Abnormalities were associated with common neonatal disorders such as
      sepsis, neonatal encephalopathy, neonatal isoerythrolysis, and prematurity. BAER
      loss also was observed in foals with specific coat color patterns such as
      completely or mostly white with blue irides or lavender with pale yellow irides.
      An American Miniature foal with marked facial deformation also lacked BAER
      bilaterally. One nonneonatal foal with an intracranial abscess had no detectable
      BAER peaks bilaterally, and 2 older foals, 1 with presumed equine protozoal
      myeloencephalitis and the other with progressive scoliosis and ataxia, had BAER
      within normal limits. CONCLUSIONS AND CLINICAL IMPORTANCE: In neonatal foals,
      BAER deficits commonly are complete and bilateral, and associated with common
      neonatal disorders and certain coat and eye color patterns. Sepsis, hypoxia,
      bilirubin toxicity, and prematurity should be investigated as potential causes of
      auditory loss in neonatal foals.

PMID- 24903743
TI  - Impaired contextual fear extinction and hippocampal synaptic plasticity in adult
      rats induced by prenatal morphine exposure.
AB  - Prenatal opiate exposure causes a series of neurobehavioral disturbances by
      affecting brain development. However, the question of whether prenatal opiate
      exposure increases vulnerability to memory-related neuropsychiatric disorders in
      adult offspring remains largely unknown. Here, we found that rats prenatally
      exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of
      contextual fear memory compared with control animals that were prenatally exposed
      to saline (PS). The impairment of acquisition was rescued by increasing the
      intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found
      that PM rats exhibited impaired extinction of contextual fear, which is
      associated with enhanced maintenance of fear memory. The impaired extinction
      lasted for 1 week following extinction training. Furthermore, PM rats exhibited
      reduced anxiety-like behavior in the elevated plus-maze and light/dark box test
      without differences in locomotor activity. These alterations in PM rats were
      mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1
      synapses of the hippocampus in vivo. PS rats showed blocked long-term
      potentiation and enabled long-term depression in CA1 synapses following
      contextual fear conditioning, while prenatal morphine exposure restricted
      synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM
      rats was not further blocked by contextual fear conditioning, and the long-term
      depression enabled by contextual fear conditioning was abolished. Taken together,
      our results provide the first evidence suggesting that prenatal morphine exposure
      may increase vulnerability to fear memory-related neuropsychiatric disorders in
      adulthood.

PMID- 24903744
TI  - GFAP out-performs S100beta in detecting traumatic intracranial lesions on
      computed tomography in trauma patients with mild traumatic brain injury and those
      with extracranial lesions.
AB  - Both glial fibrillary acidic protein (GFAP) and S100beta are found in glial cells
      and are released into serum following a traumatic brain injury (TBI), however,
      the clinical utility of S100beta as a biomarker has been questioned because of
      its release from bone. This study examined the ability of GFAP and S100beta to
      detect intracranial lesions on computed tomography (CT) in trauma patients and
      also assessed biomarker performance in patients with fractures and extracranial
      injuries on head CT. This prospective cohort study enrolled a convenience sample
      of adult trauma patients at a Level I trauma center with and without mild or
      moderate traumatic brain injury (MMTBI). Serum samples were obtained within 4 h
      of injury. The primary outcome was the presence of traumatic intracranial lesions
      on CT scan. There were 397 general trauma patients enrolled: 209 (53%) had a
      MMTBI and 188 (47%) had trauma without MMTBI. Of the 262 patients with a head CT,
      20 (8%) had intracranial lesions. There were 137 (35%) trauma patients who
      sustained extracranial fractures below the head to the torso and extremities.
      Levels of S100beta were significantly higher in patients with fractures, compared
      with those without fractures (p<0.001) whether MMTBI was present or not. However,
      GFAP levels were not significantly affected by the presence of fractures
      (p>0.05). The area under the receiver operating characteristics curve (AUC) for
      predicting intracranial lesions on CT for GFAP was 0.84 (0.73-0.95) and for
      S100beta was 0.78 (0.67-0.89). However, in the presence of extracranial
      fractures, the AUC for GFAP increased to 0.93 (0.86-1.00) and for S100beta
      decreased to 0.75 (0.61-0.88). In a general trauma population, GFAP out-performed
      S100beta in detecting intracranial CT lesions, particularly in the setting of
      extracranial fractures.

PMID- 24903745
TI  - Macrocyclic protease inhibitors with reduced peptide character.
AB  - There is a real need for simple structures that define a beta-strand
      conformation, a secondary structure that is central to peptide-protein
      interactions. For example, protease substrates and inhibitors almost universally
      adopt this geometry on active site binding. A planar pyrrole is used to replace
      two amino acids of a peptide backbone to generate a simple macrocycle that
      retains the required geometry for active site binding. The resulting beta-strand
      templates have reduced peptide character and provide potent protease inhibitors
      with the attachment of an appropriate amino aldehyde to the C-terminus. Picomolar
      inhibitors of cathepsin L and S are reported and the mode of binding of one
      example to the model protease chymotrypsin is defined by X-ray crystallography. 

PMID- 24903746
TI  - PLAB: time for evidence based change.

PMID- 24903747
TI  - Integrating genetics and epigenetics in myelodysplastic syndromes: advances in
      pathogenesis and disease evolution.
AB  - The myelodysplastic syndromes (MDS) are a group of clonal diseases characterized
      by inefficient haematopoiesis, increased apoptosis and risk of evolution to acute
      myeloid leukaemia. Alterations in epigenetic processes, including DNA
      methylation, histone modifications, miRNA and splicing machinery, are well known
      pathogenical events in MDS. Although many advances have been made in determining
      the mutational frequency, distribution and association affecting these epigenomic
      regulators, functional integration to better understand pathogenesis of the
      disease is a challenging and expanding area. Recent studies are shedding light on
      the molecular basis of myelodysplasia and how mutations and epimutations can
      induce and promote this neoplastic process through aberrant transcription factor
      function (RUNX1, ETV6, TP53), kinase signalling (FLT3, NRAS, KIT, CBL) and
      epigenetic deregulation (TET2, IDH1/2, DNMT3A, EZH2, ASXL1, SF3B1, U2AF1, SRSF2,
      ZRSR2). In this review we will try to focus on the description of these
      mutations, their impact on prognosis, the functional connections between the
      different epigenetic pathways, and the existing and future therapies targeting
      these processes. 

PMID- 24903748
TI  - Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and
      possible significance.
AB  - BACKGROUND: Small changes of bilirubin and liver enzymes are often detected
      during the acute phase of stroke, but their origin and significance are still
      poorly understood. METHODS: On days 0, 3, 7, and 14 after admission, 180 patients
      with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT,
      gammaGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count.
      On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day
      3 cerebral infarct volume (IV) was calculated from CT scan slices. RESULTS:
      During the first week GOT, GPT, gammaGT (P < 0.001) and CRP (P = 0.03) increased
      with subsequent plateau, while significant decrements (P < 0.001) concerned
      unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase,
      direct bilirubin and common bile duct diameter remained stable. IV correlated
      with CRP, leukocytes, GOT, gammaGT (r > 0.3, P < 0.001 for all) and direct
      bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT
      remained independently associated with IV (P < =0.001). The correlation of IV
      with GOT increased progressively from admission to day 14. GOT independently
      correlated with GPT which, in turn, correlated with gammaGT. gammaGT was also
      highly correlated with leukocytes. Unconjugated bilirubin correlated with
      haemoglobin, which was inversely correlated with CRP. CONCLUSIONS: The changes of
      bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which
      are both related to IV: 1) inflammation, with consequent increment of CRP,
      leukocytes and gammaGT, and decrease of haemoglobin and unconjugated bilirubin
      and 2) an unknown signal, independent from inflammation, leading to increasing
      GOT and GPT levels.

PMID- 24903749
TI  - Antiseizure effects of TrkB kinase inhibition.
AB  - OBJECTIVE: The principal molecular targets of conventional antiseizure drugs
      consist of ligand-gated and voltage-gated ion channels and proteins subserving
      synaptic function. Inhibition of the receptor tyrosine kinase TrkB limits
      epileptogenesis, but its effect on individual seizures is unknown. We sought to
      determine whether inhibition of TrkB kinase exerts an antiseizure effect.
      METHODS: We utilized the kindling model in combination with an inducible
      conditional knockout of the TrkB gene (Act-CreER TrkB(flox/flox) mice treated
      with tamoxifen), and also with a chemical-genetic approach in which mice carry a
      TrkB kinase with a phenylalanine to alanine substitution of residue 616 (TrkB(F)
      (616A) ), which allows inhibition of the kinase by a blood-brain barrier
      permeable small molecule, 1'-naphthylmethyl-4-amino-1-tert-butyl-3-(p
      methylphenyl)pyrazolo[3,4-d]pyrimidine (1NMPP1). RESULTS: Following induction of
      kindling, reduction of TrkB protein levels in Act-CreER TrkB(flox/flox) mice
      treated with tamoxifen was associated with reduced severity of behavioral
      seizures evoked by stimulation. Treatment with 1NMPP1 for 2 weeks following
      induction of kindling reversibly elevated both focal electrographic and
      generalized seizure thresholds in TrkB(F) (616A) , but not wild-type (WT), mice.
      In contrast to kindled animals, treatment of naive TrkB(F) (616A) mice for 2
      weeks had no detectable effect on electrographic seizure threshold (EST).
      SIGNIFICANCE: This study provides proof of concept of a novel molecular target
      for antiseizure drugs, namely the receptor tyrosine kinase TrkB.

PMID- 24903751
TI  - Mitochondrial perturbation negatively affects auxin signaling.
AB  - Mitochondria are crucial players in the signaling and metabolic homeostasis of
      the plant cell. The molecular components that orchestrate the underlying
      processes, however, are largely unknown. Using a chemical biology approach, we
      exploited the responsiveness of Arabidopsis UDP-glucosyltransferase-encoding
      UGT74E2 towards mitochondrial perturbation in order to look for novel mechanisms
      regulating mitochondria-to-nucleus communication. The most potent inducers of
      UGT74E2 shared a (2-furyl)acrylate (FAA) substructure that negatively affected
      mitochondrial function and was identified before as an auxin transcriptional
      inhibitor. Based on these premises, we demonstrated that perturbed mitochondria
      negatively affect the auxin signaling machinery. Moreover, chemical perturbation
      of polar auxin transport and auxin biosynthesis was sufficient to induce
      mitochondrial retrograde markers and their transcript abundance was
      constitutively elevated in the absence of the auxin transcriptional activators
      ARF7 and ARF19. 

PMID- 24903750
TI  - Case-control study of breast cancer in India: Role of PERIOD3 clock gene length
      polymorphism and chronotype.
AB  - BACKGROUND: This study examined a PERIOD3 (PER3) gene variable number tandem
      repeat polymorphism and chronotype as potential BrCA risk factors among Indian
      women. METHODS: This case-control study included sporadic, histologically
      confirmed BrCA cases (n = 255) and controls (n = 249) from India with data
      collection from 2010-2012. RESULTS: Women with the 4/5 or 5/5 PER3 genotype had a
      nonstatistically significant 33% increased odds of BrCA. Cases were more likely
      to have a morning (OR = 2.43, 95% CI = 1.23-4.81) or evening (OR = 2.55, 95% CI =
      1.19-5.47) chronotype. CONCLUSIONS: Findings are consistent with the possibility
      that extremes in chronotype may elicit circadian desynchronization, resulting in
      increased BrCA susceptibility.

PMID- 24903752
TI  - Vegfd can compensate for loss of Vegfc in zebrafish facial lymphatic sprouting.
AB  - Lymphangiogenesis is a dynamic process that involves the sprouting of lymphatic
      endothelial cells (LECs) from veins to form lymphatic vessels. Vegfr3 signalling,
      through its ligand Vegfc and the extracellular protein Ccbe1, is essential for
      the sprouting of LECs to form the trunk lymphatic network. In this study we
      determined whether Vegfr3, Vegfc and Ccbe1 are also required for development of
      the facial and intestinal lymphatic networks in the zebrafish embryo. Whereas
      Vegfr3 and Ccbe1 are required for the development of all lymphatic vessels, Vegfc
      is dispensable for facial lymphatic sprouting but not for the complete
      development of the facial lymphatic network. We show that zebrafish vegfd is
      expressed in the head, genetically interacts with ccbe1 and can rescue the
      lymphatic defects observed following the loss of vegfc. Finally, whereas
      knockdown of vegfd has no phenotype, double knockdown of both vegfc and vegfd is
      required to prevent facial lymphatic sprouting, suggesting that Vegfc is not
      essential for all lymphatic sprouting and that Vegfd can compensate for loss of
      Vegfc during lymphatic development in the zebrafish head. 

PMID- 24903753
TI  - Without children is required for Stat-mediated zfh1 transcription and for
      germline stem cell differentiation.
AB  - Tissue homeostasis is maintained by balancing stem cell self-renewal and
      differentiation. How surrounding cells support this process has not been entirely
      resolved. Here we show that the chromatin and telomere-binding factor Without
      children (Woc) is required for maintaining the association of escort cells (ECs)
      with germ cells in adult ovaries. This tight association is essential for
      germline stem cell (GSC) differentiation into cysts. Woc is also required in
      larval ovaries for the association of intermingled cells (ICs) with primordial
      germ cells. Reduction in the levels of two other proteins, Stat92E and its target
      Zfh1, produce phenotypes similar to woc in both larval and adult ovaries,
      suggesting a molecular connection between these three proteins. Antibody staining
      and RT-qPCR demonstrate that Zfh1 levels are increased in somatic cells that
      contact germ cells, and that Woc is required for a Stat92E-mediated upregulation
      of zfh1 transcription. Our results further demonstrate that overexpression of
      Zfh1 in ECs can rescue GSC differentiation in woc-deficient ovaries. Thus, Zfh1
      is a major Woc target in ECs. Stat signalling in niche cells has been previously
      shown to maintain GSCs non-autonomously. We now show that Stat92E also promotes
      GSC differentiation. Our results highlight the Woc-Stat-Zfh1 module as promoting
      somatic encapsulation of germ cells throughout their development. Each somatic
      cell type can then provide the germline with the support it requires at that
      particular stage. Stat is thus a permissive factor, which explains its apparently
      opposite roles in GSC maintenance and differentiation. 

PMID- 24903755
TI  - Embryonic toxicity of nanoparticles.
AB  - Applications of nanoparticles (NP) in medicine, industry and other branches of
      human activities undoubtedly contribute to technology development and well-being.
      However, as NP are very small units in a wide range of materials, there is a lack
      of information related to possible side effects potentially affecting the health
      of organisms. There is increasing experimental interest in the determination of
      environmental effects on humans exposed to NP. Most such experimental studies
      focus on adult populations or adult experimental animals. However, embryos can be
      more sensitive to pollutants and environmental impacts in some species.
      Therefore, some investigations dealing particularly with the effects of NP on
      embryonic development have appeared recently and this issue is becoming of great
      concern. The aim of this review is to summarize the knowledge on the effects of
      various nanomaterials on embryonic development. A comprehensive collection of
      significant experimental nanotoxicity data is presented, which also indicate how
      the toxic effect of NP can be mediated and modulated with respect to possible
      effective protection strategies.

PMID- 24903756
TI  - In vivo study of targeted nanomedicine delivery into Langerhans cells by
      multiphoton laser scanning microscopy.
AB  - Epidermal Langerhans cells (LCs) function as professional antigen-presenting
      cells of the skin. We investigated the LC-targeting properties of a special
      mannose-moiety-coated pathogen-like synthetic nanomedicine DermaVir (DV), which
      is capable to express antigens to induce immune responses and kill HIV-infected
      cells. Our aim was to use multiphoton laser microscopy (MLM) in vivo in order to
      visualize the uptake of Alexa-labelled DV (AF546-DV) by LCs. Knock-in mice
      expressing enhanced green fluorescent protein (eGFP) under the control of the
      langerin gene (CD207) were used to visualize LCs. After 1 h, AF546-DV penetrated
      the epidermis and entered the eGFP-LCs. The AF546-DV signal was equally
      distributed inside the LCs. After 9 h, we observed AF546-DV signal accumulation
      that occurred mainly at the cell body. We demonstrated in live animals that LCs
      picked up and accumulated the nanoparticles in the cell body. 

PMID- 24903754
TI  - PIWI homologs mediate histone H4 mRNA localization to planarian chromatoid
      bodies.
AB  - The well-known regenerative abilities of planarian flatworms are attributed to a
      population of adult stem cells called neoblasts that proliferate and
      differentiate to produce all cell types. A characteristic feature of neoblasts is
      the presence of large cytoplasmic ribonucleoprotein granules named chromatoid
      bodies, the function of which has remained largely elusive. This study shows that
      histone mRNAs are a common component of chromatoid bodies. Our experiments also
      demonstrate that accumulation of histone mRNAs, which is typically restricted to
      the S phase of eukaryotic cells, is extended during the cell cycle of neoblasts.
      The planarian PIWI homologs SMEDWI-1 and SMEDWI-3 are required for proper
      localization of germinal histone H4 (gH4) mRNA to chromatoid bodies. The
      association between histone mRNA and chromatoid body components extends beyond
      gH4 mRNA, since transcripts of other core histone genes were also found in these
      structures. Additionally, piRNAs corresponding to loci of every core histone type
      have been identified. Altogether, this work provides evidence that links PIWI
      proteins and chromatoid bodies to histone mRNA regulation in planarian stem
      cells. The molecular similarities between neoblasts and undifferentiated cells of
      other organisms raise the possibility that PIWI proteins might also regulate
      histone mRNAs in stem cells and germ cells of other metazoans. 

PMID- 24903757
TI  - Feline upper respiratory tract lymphoma: site, cyto-histology, phenotype, FeLV
      expression, and prognosis.
AB  - Lymphoma is the most common feline upper respiratory tract (URT) tumor. Primary
      nasal and nasopharyngeal lymphomas have been evaluated as distinct pathological
      entities; however, data on their differing clinical behavior are missing. A total
      of 164 endoscopic- guided URT pinch biopsies were formalin fixed and routinely
      processed. Imprint cytological specimens were stained with May Grunwald-Giemsa.
      Immunohistochemistry for anti-CD20, CD3, FeLVp27, and FeLVgp70 was performed.
      Prognostic significance of clinicopathological variables was investigated by
      univariate and multivariate analysis. Lymphoma was diagnosed in 39 cats (24%).
      Most cats with lymphoma were domestic shorthair (32 [82%]), were male (F/M =
      0.56), and had a mean age of 10.3 years (range, 1-16 years). Lymphomas were
      primary nasal in 26 cats (67%), nasopharyngeal in 6 (15%), and in both locations
      (combined lymphomas) in 7 cats (18%). Neoplastic growth pattern was diffuse in 35
      cases (90%) and nodular in 4 (10%). Epitheliotropism was observed in 10 cases
      (26%). Tumor cells were large in 15 cases, were small and medium in 11 cases
      each, and 2 had mixed cell size. Submucosal lymphoplasmacytic inflammation was
      observed in 23 cases (59%). Cytology was diagnostic for lymphoma in 12 of 25
      cases (48%). A B-cell origin prevailed (34 [87%]). Feline leukemia virus (FeLV)
      p27 or gp70 antigen was detected in 21 lymphomas (54%). URT lymphomas were
      aggressive, with survival varying from 0 to 301 days (mean, 53 days).
      Epitheliotropism in 8 B-cell lymphomas (80%) and in 2 T-cell lymphomas (20%)
      correlated with prolonged survival. Age younger or older than 10 years had a
      negative prognostic value. Lymphoplasmacytic inflammation and FeLV infection may
      represent favoring factors for URT lymphoma development.

PMID- 24903758
TI  - Nutrition for swimming.
AB  - Swimming is a sport that requires considerable training commitment to reach
      individual performance goals. Nutrition requirements are specific to the
      macrocycle, microcycle, and individual session. Swimmers should ensure suitable
      energy availability to support training while maintaining long term health.
      Carbohydrate intake, both over the day and in relation to a workout, should be
      manipulated (3-10 g/kg of body mass/day) according to the fuel demands of
      training and the varying importance of undertaking these sessions with high
      carbohydrate availability. Swimmers should aim to consume 0.3 g of high
      biological-value protein per kilogram of body mass immediately after key sessions
      and at regular intervals throughout the day to promote tissue adaptation. A mixed
      diet consisting of a variety of nutrient-dense food choices should be sufficient
      to meet the micronutrient requirements of most swimmers. Specific dietary
      supplements may prove beneficial to swimmers in unique situations, but should be
      tried only with the support of trained professionals. All swimmers, particularly
      adolescent and youth swimmers, are encouraged to focus on a well-planned diet to
      maximize training performance, which ensures sufficient energy availability
      especially during periods of growth and development. Swimmers are encouraged to
      avoid rapid weight fluctuations; rather, optimal body composition should be
      achieved over longer periods by modest dietary modifications that improve their
      food choices. During periods of reduced energy expenditure (taper, injury, off
      season) swimmers are encouraged to match energy intake to requirement. Swimmers
      undertaking demanding competition programs should ensure suitable recovery
      practices are used to maintain adequate glycogen stores over the entirety of the
      competition period.

PMID- 24903759
TI  - Factors Affecting Seroconversion Rates in Cattle Vaccinated with Two Commercial
      Inactivated BTV-8 Vaccines Under Field Conditions.
AB  - The immunogenicity of two inactivated bluetongue virus serotype 8 (BTV-8)
      vaccines was evaluated in 880 cattle under field conditions. The effect of
      selected factors on vaccine performance was also analysed at the herd and animal
      levels (vaccine, herd size and production, age, sex, time interval between
      vaccination and blood sampling and veterinary training). The immunogenicity
      elicited by vaccination with the two vaccines was monitored with the aid of a
      competitive enzyme-linked immunosorbent assay (c-ELISA) and serum neutralization
      test (SNT). To investigate whether the selected factors influenced seroconversion
      at the herd and animal levels, a multilevel logistic regression model developed
      in a mixed model was applied. Of the 880 cattle vaccinated, 76.0% yielded BTV c
      ELISA antibodies, whereas only 25.0% seroconverted based on SNT. Type of vaccine
      (odds ratio [OR] 4.5; 95% confidence interval [CI], 2.2-9.0 for SNT and OR 3.5;
      95% CI, 2.1-5.9 for c-ELISA), veterinary training in vaccine administration (OR
      8.1; 95% CI, 4.7-14.1 for SNT and OR 2.4; 95% CI, 1.3-4.2 for c-ELISA), animal
      age (OR 1.4; 95% CI, 1.1-1.8 for SNT and OR 1.7; 95% CI, 1.4-2.1 for c-ELISA) and
      days between first vaccine administration and blood collection (OR 1.9; 95% CI,
      1.1-3.1 for SNT and OR 2.6; 95% CI, 1.7-3.8 for c-ELISA) were the major factors
      affecting vaccine performance under field conditions. This is the first study to
      use multilevel logistic regression in the evaluation of selected risk factors
      affecting BTV-8 vaccine performance in cattle. 

PMID- 24903760
TI  - Online survey of cancer patients on complementary and alternative medicine.
AB  - INTRODUCTION: Complementary and alternative medicine (CAM) is often used by
      cancer patients, yet, communication with the oncologist is poor. The objective of
      our study was to gather information on patients' usage of CAM, source of
      information, and aims, in order to derive strategies to improve the communication
      between physicians and patients on this topic. MATERIALS AND METHODS: An online
      survey was conducted by linking a standardized questionnaire to the largest
      internet portal for cancer patients in Germany. The questionnaire addresses CAM
      usage, disclosure to physicians, source of information, objectives for using CAM,
      and perceived reasons for cancer. RESULTS: Of 170 participants, 77% were
      currently using CAM. Disclosure to a physician was rather high with 63% having
      informed their oncologist. Asked whether the oncologist took time to discuss CAM,
      74% answered 'no'. Most frequently used are biologically based therapies,
      relaxation techniques, prayer, and meditation. Most patients want to reduce side
      effects, boost their immune system, and get active. Almost half the participants
      had positive experiences with some type of CAM before they fell ill. CONCLUSION:
      Understanding patients' concepts of the etiology of cancer and accepting their
      goals for using CAM may help oncologists communicate with their patients and
      guide them to a safe use of CAM.

PMID- 24903761
TI  - Influence of socioeconomic status on survival and clinical outcomes in patients
      with advanced gastric cancer after chemotherapy.
AB  - BACKGROUND: Socioeconomic inequalities are known to influence the survival of
      cancer patients due to differences in treatment modalities and disease extent at
      diagnosis. However, there are few studies regarding the influence of
      socioeconomic status on patient survival, especially after palliative
      chemotherapy for advanced gastric cancer. PATIENTS AND METHODS: This
      retrospective study was performed on 138 advanced gastric cancer patients who
      received palliative chemotherapy. Demographic, socioeconomic, and cancer-related
      variables were analyzed according to education level. Effects of socioeconomic
      factors and cancer-related variables on patient survival were also evaluated.
      RESULTS: In our study, higher education level (> 6 years of schooling; p = 0.01),
      disease control (p < 0.01), and a greater number of chemotherapeutic agents (>= 5
      drugs; p < 0.01) were associated with a significant increase in median survival.
      Multivariate analysis showed that a higher education level (hazard ratio (HR)
      0.53; 95% confidence interval (CI) 0.35-0.82; p < 0.01), disease control (HR
      0.21; 95% CI 0.13-0.34), and total number of chemotherapeutic agents used (HR
      0.44; 95% CI 0.26-0.73) were significantly associated with prolonged survival.
      CONCLUSIONS: Among socioeconomic factors, only higher education level was
      associated with better survival. Increase in survival was also associated with
      clinical outcomes, including total number of chemotherapeutic agents used and
      disease control after chemotherapy.

PMID- 24903762
TI  - Best supportive care from the conservative/non-surgical perspective and its costs
      in the treatment of patients with advanced medullary thyroid cancer: results of a
      Delphi panel.
AB  - BACKGROUND: Medullary thyroid cancer (MTC) is a rare tumor entity. The contents
      of best supportive care (BSC) have not been defined in advanced MTC. The
      objective of this work is to describe the epidemiology, the treatment patterns
      with respect to symptom management, as well as palliative treatment and
      associated costs. METHOD: A Delphi panel with 9 clinical experts experienced in
      treating MTC was conducted to obtain details on the epidemiology of MTC and to
      gain insights into the therapeutic options considered for BSC in advanced MTC in
      Germany. Unit costs were applied to the described resources from the perspective
      of the German National Healthcare System in 2011. RESULTS: The annual incidence
      of MTC in Germany was estimated at about 220. 32% of all patients were estimated
      to have aggressive/symptomatic MTC, with an estimated mean survival of 36.7
      months (median: 36 months). The core element of BSC is relief of symptoms to
      maintain quality of life. The total mean cost of BSC per patient/year was
      estimated at ? 9,248, lifetime cost at ? 28,283. CONCLUSION: There was consistent
      agreement within the panel on the epidemiology of MTC and on the structure of the
      provided therapeutic measures for BSC in advanced MTC, also defining the
      management of symptoms as a crucial goal of treatment.

PMID- 24903763
TI  - Image-guided radiation therapy based on helical tomotherapy in prostate cancer:
      minimizing toxicity.
AB  - BACKGROUND: We report the clinical results and prognostic factors of image-guided
      radiation therapy (RT) with helical tomotherapy (HT) for localized and recurrent
      prostate cancer (PC). PATIENTS AND METHODS: We evaluated 70 patients with PC
      (primary diagnosis, n = 48; adjuvant, n = 5; salvage, n = 17) treated with HT
      from May 2006 through January 2011. The dose prescribed to the prostate/surgical
      bed ranged between 60 and 78 Gy. Potential risk factors for genitourinary (GU)
      and gastrointestinal (GI) toxicity were assessed. RESULTS: The median age was 68
      years (range 51-87 years). The median follow-up was 37 months (range 3-74
      months). The rates of acute grade 2 GI and GU toxicities were 10 and 13%,
      respectively. Only 1 patient experienced acute grade 3 GU toxicity. The rates of
      late grade >= 2 GI and GU toxicities were 1% each. Multivariate analysis showed
      an association between rectum mean dose > median (39 Gy) and bladder median dose
      > median (46 Gy) with a higher grade of acute GI (p = 0.017) and GU (p = 0.019)
      toxicity, respectively. Additionally, older age was associated with late GU
      toxicity (p = 0.026). CONCLUSION: Toxicity with HT is low and is associated with
      higher median/mean doses in organs at risk as well as with older age. A
      prospective validation would be necessary to confirm these results.

PMID- 24903764
TI  - Treatment and prognostic factors in primary peritoneal carcinoma: a multicenter
      study of the Anatolian Society of Medical Oncology (ASMO).
AB  - BACKGROUND: In this study, we aimed to evaluate the clinicopathological
      characteristics and prognosis of patients with primary peritoneal carcinoma
      (PPC), and the effectiveness and toxicity of first-line platinum/taxane
      combination therapy. PATIENTS AND METHODS: We retrospectively evaluated 79
      patients with PPC, who were treated and followed up between December 2001 and
      August 2012 at 10 medical oncology clinics. RESULTS: All patients were female,
      with a median age of 63 years (range 34-79 years). Histopathological diagnoses
      included primary peritoneal serous carcinoma (PPSC) (n = 69) and mixed epithelial
      carcinoma of the peritoneum (MEC) (n = 10). Patients received first-line
      treatment with carboplatin/paclitaxel (n = 67) or cisplatin/paclitaxel (n = 12)
      combination therapy. Overall response rate, median progression-free survival, and
      median survival time in the paclitaxel/carboplatin group and the
      paclitaxel/cisplatin group were 74.6 vs. 75%, 15.6 vs. 37.8 months, and 41 vs.
      70.3 months, respectively. In multivariate analysis, favorable prognostic factors
      were: ECOG performance status 0 (p < 0.001) and optimal cytoreduction (p = 0.03).
      CONCLUSION: PPC is a rare, heterogeneous disease. ECOG performance status and
      optimal cytoreduction are important prognostic factors regarding survival rates.
      Platinum/taxane combination therapy is an effective and tolerable regimen in this
      patient group.

PMID- 24903765
TI  - Relationship between serum soluble vascular adhesion protein-1 level and gastric
      cancer prognosis.
AB  - BACKGROUND: Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates
      tissue-selective lymphocyte adhesion in a sialic acid-dependent manner. The
      prognostic importance of VAP-1 was determined in various human cancers. The aim
      of this study was to determine the relationship between VAP-1 and prognosis of
      gastric cancer. MATERIALS AND METHODS: Serum of operable and metastatic gastric
      cancer patients was collected before treatment (surgery, radiotherapy, and/or
      chemotherapy). VAP-1 levels were measured by enzyme-linked immunosorbent assay.
      RESULTS: A total of 86 gastric cancer patients (32 female, 54 male) were included
      in the study. Curative surgical treatment was performed in 54 (62.8%) patients.
      The mean serum VAP-1 level was 324.4 pg/ml and significantly higher in operable
      gastric cancer patients compared to metastatic gastric cancer patients (383.1 +/-
      173.5 vs. 225.2 +/- 113.9 pg/ml; p < 0.001). When a cut-off value for VAP-1 of
      218.8 pg/ml was determined by receiver operating characteristic (ROC) curves for
      presence of metastasis, sensitivity and specificity were 81.5 and 65.6%,
      respectively. Patients with decreased VAP-1 levels had a significantly poorer
      prognosis compared to patients with increased serum VAP-1 levels (median survival
      8.2 vs. 23.5 months; p < 0.001). Multivariate analysis showed that VAP-1 is an
      independent prognostic factor of gastric cancer (odds ratio 2.3, 95% confidence
      interval 1.1-4.9; p = 0.032). CONCLUSION: A low serum VAP-1 level may be an
      indicator of poor prognosis in gastric cancer. This study demonstrated that low
      serum VAP-1 levels are associated with poor prognosis in gastric cancer patients.

PMID- 24903766
TI  - Role of the VDR Bsm I and Apa I polymorphisms in the risk of colorectal cancer in
      Kashmir.
AB  - OBJECTIVE: A case-control study aiming to evaluate the relationship between Bsm I
      and Apa I restriction fragment gene polymorphisms and colorectal cancer (CRC) was
      carried out in Kashmir, including a total of 368 subjects (180 cases and 188
      controls). METHODS: DNA samples extracted from the blood of the subjects were
      analyzed for 3' untranslated region (3' UTR) Apa I and Bsm I polymorphisms using
      restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR).
      RESULTS: A statistically significant 2.7-fold increased risk was observed in
      individuals found homozygous for the presence of the 'b' allele, in comparison to
      subjects homozygous for the 'B' allele (odds ratio (OR) 2.7, 95% confidence
      interval (CI) 1.49-4.86 (Bsm I)), and a statistically insignificant 2-fold
      increased risk was found among individuals with the 'aa' genotype, as compared to
      subjects with the 'AA' genotype (OR 2.017, 95% CI 0.86-4.7). Our study also
      yielded statistically significant results when the Apa I polymorphism was
      stratified by age (<= 50 years) and dwelling area (rural area), and the Bsm I
      polymorphism by gender (male gender), suggesting a possible role of Apa I and Bsm
      I polymorphisms in the etiology of CRC in Kashmir. CONCLUSION: We conclude that
      Apa I and Bsm I single-nucleotide polymorphisms (SNPs) in the vitamin D receptor
      gene (VDR) might be associated with susceptibility to CRC among Kashmiris.

PMID- 24903767
TI  - New-onset mediastinal and central nervous system sarcoidosis in a patient with
      metastatic melanoma undergoing CTLA4 monoclonal antibody treatment.
AB  - BACKGROUND: Ipilimumab, a cytotoxic monoclonal antibody that inhibits cytotoxic T
      lymphocyte-associated antigen-4 (CTLA-4), has been established as an effective
      therapy in the management of advanced melanoma. Immune-mediated adverse events
      are a common side effect. CASE REPORT: A 37-year-old male patient was diagnosed
      with nodal and osseous metastatic melanoma 15 months after the initial surgical
      treatment for lower limb melanoma. Therapy with the anti-CTLA-4 antibody,
      ipilimumab, was started. Follow-up staging imaging after treatment initiation
      showed symmetrical bihilar adenopathy. Transbronchial biopsy showed sarcoidosis.
      The patient had associated systemic symptoms of fatigue, joint pains, anorexia
      and weight loss. Brain magnetic resonance imaging (MRI), which was performed for
      the investigation of headaches, showed abnormal enhancing tissue in the sella
      turcica and adjacent to the pituitary infundibulum, consistent with
      neurosarcoidosis. The condition was successfully treated with corticosteroids.
      CONCLUSIONS: We report a case of immunotherapy-induced mediastinal/hilar
      sarcoidosis, with pituitary involvement, mimicking tumour progression. This
      highlights the need for awareness amongst radiologists and oncologists of the
      mechanism of action and potential side effects of new immunotherapies.

PMID- 24903768
TI  - Soft tissue sarcoma: an update on systemic treatment options for patients with
      advanced disease.
AB  - Sarcomas are a group of rare solid tumours arising from mesenchymal or connective
      tissue. This review focuses on soft tissue sarcoma and covers general topics such
      as the epidemiology, age distribution, site of disease, histogenesis,
      histological subtypes, prognosis and outcome of treatment. In more detail, the
      article reviews current systemic treatment standards and selected adverse events
      of agents such as doxorubicin, ifosfamide, trabectedin and pazopanib, and briefly
      highlights some drugs that are used off-label in specific subtypes of sarcoma.

PMID- 24903769
TI  - Emerging new markers of stroke risk and prognosis.

PMID- 24903770
TI  - Maternal immunity enhances Mycoplasma hyopneumoniae vaccination induced cell
      mediated immune responses in piglets.
AB  - BACKGROUND: Passively acquired maternal derived immunity (MDI) is a double-edged
      sword. Maternal derived antibody-mediated immunity (AMI) and cell-mediated
      immunity (CMI) are critical immediate defenses for the neonate; however, MDI may
      interfere with the induction of active immunity in the neonate, i.e. passive
      interference. The effect of antigen-specific MDI on vaccine-induced AMI and CMI
      responses to Mycoplasma hyopneumoniae (M. hyopneumoniae) was assessed in neonatal
      piglets. To determine whether CMI and AMI responses could be induced in piglets
      with MDI, piglets with high and low levels of maternal M. hyopneumoniae-specific
      immunity were vaccinated against M. hyopneumoniae at 7 d of age. Piglet M.
      hyopneumoniae-specific antibody, lymphoproliferation, and delayed type
      hypersensitivity (DTH) responses were measured 7 d and 14 d post vaccination.
      RESULTS: Piglets with M. hyopneumoniae-specific MDI failed to show vaccine
      induced AMI responses; there was no rise in M. hyopneumoniae antibody levels
      following vaccination of piglets in the presence of M. hyopneumoniae-specific
      MDI. However, piglets with M. hyopneumoniae-specific MDI had primary (antigen
      specific lymphoproliferation) and secondary (DTH) M. hyopneumoniae-specific CMI
      responses following vaccination. CONCLUSIONS: In this study neonatal M.
      hyopneumoniae-specific CMI was not subject to passive interference by MDI.
      Further, it appears that both maternal derived and endogenous CMI contribute to
      M. hyopneumoniae-specific CMI responses in piglets vaccinated in the face of MDI.

PMID- 24903773
TI  - Broadening the scope of Baeyer-Villiger monooxygenase activities toward
      alpha,beta-unsaturated ketones: a promising route to chiral enol-lactones and ene
      lactones.
AB  - Three regiodivergent Baeyer-Villiger mono-oxygenases (enantioselectively)
      oxidized a series of cyclic alpha,beta-unsaturated ketones into (chiral) either
      enol-lactones or ene-lactones. An easy-to-use and efficient biocatalytic process
      based on a host-microorganism deprived of unwanted activities (knock-out mutant)
      was developed to enable the exclusive synthesis of unsaturated lactones. 

PMID- 24903772
TI  - Serotonin-related polymorphisms in TPH1 and HTR5A genes are not associated with
      escitalopram treatment response in Korean patients with major depression.
AB  - BACKGROUND/AIMS: The genetic variations in serotonin-related genes may be
      associated with antidepressant treatment response in major depressive disorder
      (MDD). The tryptophan hydroxylase-1 (TPH1) gene and serotonin 5A receptor (HTR5A)
      gene are known to be involved in serotonin biosynthesis and signal transduction,
      respectively. The purpose of this study was to investigate a possible interaction
      between the TPH1 gene and the HTR5A gene in the treatment outcome of escitalopram
      in MDD. METHODS: In total, 245 patients diagnosed with MDD were recruited, and
      their symptoms were evaluated using the 17-item Hamilton Depression Rating scale
      (HAMD-17). The association between the TPH1 218A/C and HTR5A 12A/T polymorphisms
      and the clinical outcomes (remission, response and changes in HAMD-17 score) was
      investigated after 2, 4 and 8 weeks of escitalopram treatment using multiple
      logistic regression or multiple linear regression analysis. RESULTS: No
      significant associations of TPH1 or HTR5A gene polymorphisms were observed with
      either response rate or remission rate at 2, 4 and 8 weeks after escitalopram
      treatment. In addition, the gene-gene interaction between TPH1 and HTR5A genes
      was not associated with the treatment outcome. CONCLUSIONS: Our results suggest
      that TPH1 218A/C and HTR5A 12A/T polymorphisms cannot predict treatment response
      in major depression.

PMID- 24903771
TI  - The prediction of study-emergent suicidal ideation in bipolar disorder: a pilot
      study using ecological momentary assessment data.
AB  - OBJECTIVES: Bipolar disorder is associated with idiosyncratic precursors of
      clinically important states such as suicidal ideation. Ecological momentary
      assessment (EMA) - high frequency data collection in a subject's usual
      environment - provides the potential for development of temporal, individualized
      prediction of risk states. The present study tested the ability of EMA data to
      predict individual symptom change in clinician-rated suicidal ideation. METHODS:
      Thirty-five adults diagnosed with inter-episode bipolar disorder completed daily
      measures of affect in their home environments using diaries administered over an
      eight-week assessment timeline. Suicidal ideation was assessed monthly at in
      person visits using the Inventory of Depressive Symptomatology-Clinician Rated.
      We used a novel application of functional linear models (FLMs) to generate
      prospective predictions of suicidal ideation at in-person clinician assessments
      based on intensively sampled trajectories of daily affect. RESULTS: Eight
      instances of suicidal ideation scores > 0 were recorded during the study period
      on six participants. Utilizing trajectories of negative and positive affect,
      cross-validated predictions attained 88% sensitivity with 95% specificity for
      elevated suicidal ideation one week prior to in-person clinician assessment. This
      model strongly outperformed prediction models using cross-sectional data obtained
      at study visits alone. CONCLUSIONS: Utilizing EMA data with FLM prediction models
      substantially increases the accuracy of prediction of study-emergent suicidal
      ideation. Prediction algorithms employing intensively sampled longitudinal EMA
      data could sensitively detect the warning signs of suicidal ideation to
      facilitate improved suicide risk assessment and the timely delivery of
      preventative interventions.

PMID- 24903774
TI  - Marangoni self-propelled capsules in a maze: pollutants 'sense and act' in
      complex channel environments.
AB  - Environmental remediation is a highly pressing issue in society. Here we
      demonstrate that autonomous self-propelled millimeter sized capsules can sense
      the presence of pollutants, mark sites for visible identification and remove the
      contamination, while navigating in a complex environment of interconnected
      channels, the maze. Such long-range self-powered capsules propelled by the
      Marangoni effect are capable of releasing chemicals to alter the pH and induce
      aggregation during pollutant flocculation at a faster rate than convection or
      diffusion. These devices are foreseen to have real-world environmental
      applications in the near future. 

PMID- 24903775
TI  - Semi automated transformation to OWL formatted files as an approach to data
      integration. A feasibility study using environmental, disease register and
      primary care clinical data.
AB  - INTRODUCTION: This article is part of the Focus Theme of METHODS of Information
      in Medicine on "Managing Interoperability and Complexity in Health Systems".
      BACKGROUND: Data heterogeneity is one of the critical problems in analysing,
      reusing, sharing or linking datasets. Metadata, whilst adding semantic
      description to data, adds an additional layer of complexity in the heterogeneity
      of metadata descriptors themselves. This can be managed by using a pre-defined
      model to extract the metadata, but this can reduce the richness of the data
      extracted. OBJECTIVES: to link the South London Stroke Register (SLSR), the
      London Air Pollution toolkit (LAP) and the Clinical Practice Research Datalink
      (CPRD) while transforming data into the Web Ontology Language (OWL) format.
      METHODS: We used a four-step transformation approach to prepare meta
      descriptions, convert data, generate and update meta-classes and generate OWL
      files. We validated the correctness of the transformed OWL files by issuing
      queries and assessing results against the original source data. RESULTS: We have
      transformed SLSR LAP and CPRD into OWL format. The linked SLSR and CPRD OWL file
      contains 3644 male and 3551 female patients. The linked SLSR and LAP OWL file
      shows that there are 17 out of 35 outward postcode areas, where no overlapping
      data can support further analysis between SLSR and LAP. CONCLUSIONS:  Our
      approach generated a resultant set of transformed OWL formatted files, which are
      in a query-able format to run individual queries, or can be easily converted into
      other more suitable formats for further analysis, and the transformation was
      faithful with no loss or anomalies. Our results have shown that the proposed
      method provides a promising general approach to address data heterogeneity.

PMID- 24903777
TI  - Can you trust your animal study data?

PMID- 24903778
TI  - LIMK1 is involved in the protective effects of bone morphogenetic protein 6
      against amyloid-beta-induced neurotoxicity in rat hippocampal neurons.
AB  - Bone morphogenetic protein 6 (BMP6) has neuroprotective effects against various
      neuronal injuries, but its effect on amyloid-beta (Abeta)-induced neurotoxicity
      remains unclear. We exposed rat hippocampal neurons to different concentrations
      of Abeta25-35 to induce neurotoxicity, and then treated cells with BMP6 to assess
      the neuroprotective effects. In vivo, we bilaterally injected Abeta1-40 into
      basal forebrain to simulate the neuropathological process of Alzheimer's disease
      (AD), and explored changes in the expression of BMP6 and LIMK1. Our data
      demonstrated that BMP6 prevented apoptosis induced by a high dose of Abeta25-35,
      and inhibited rod formation induced by low dose of Abeta25-35 in hippocampal
      neurons. Forebrain injection of Abeta1-40 led to a significant downregulation of
      BMP6, and inactivation of LIMK1 pathway in basal forebrain, whereas the opposite
      changes were observed in hippocampus. Our results suggest that BMP6 has
      neuroprotective effects against Abeta25-35. The BMP6 and LIMK1 pathways may have
      different expression patterns at different stages of AD, and be self-regulating
      via a negative feedback mechanism between different brain regions. 

PMID- 24903779
TI  - Concordance between direct and imputed APOE genotypes using 1000 Genomes data.
AB  - There are a growing number of large cohorts of older persons with genome-wide
      genotyping data available, but APOE is not included in any of the common
      microarray platforms. We compared directly measured APOE genotypes with those
      imputed using microarray data and the "1000 Genomes" dataset in a sample of 320
      Caucasians. We find 90% agreement for epsilon2/epsilon3/epsilon4 genotypes and
      93% agreement for predicting epsilon4 status, yielding kappa values of 0.81 and
      0.84, respectively. More stringent thresholds around allele number estimates can
      increase this agreement to 90-97% and kappas of 0.90-0.93.

PMID- 24903776
TI  - Muscarinic acetylcholine receptors: novel opportunities for drug development.
AB  - The muscarinic acetylcholine receptors are a subfamily of G protein-coupled
      receptors that regulate numerous fundamental functions of the central and
      peripheral nervous system. The past few years have witnessed unprecedented new
      insights into muscarinic receptor physiology, pharmacology and structure. These
      advances include the first structural views of muscarinic receptors in both
      inactive and active conformations, as well as a better understanding of the
      molecular underpinnings of muscarinic receptor regulation by allosteric
      modulators. These recent findings should facilitate the development of new
      muscarinic receptor subtype-selective ligands that could prove to be useful for
      the treatment of many severe pathophysiological conditions. 

PMID- 24903780
TI  - Cognitive enhancers (nootropics). Part 2: drugs interacting with enzymes. Update
      2014.
AB  - Scientists working in the field of Alzheimer's disease and, in particular,
      cognitive enhancers are very productive. The review on Drugs interacting with
      Enzymes was accepted in August 2012. However, this field is very dynamic. New
      potential targets for the treatment of Alzheimer's disease were identified. This
      update describes drugs interacting with 60 enzymes versus 43 enzymes in the first
      paper. Some compounds progressed in their development, while many others were
      discontinued. The present review covers the evolution of research in this field
      through April 2014. 

PMID- 24903781
TI  - World Asthma Day. GINA 2014: a global asthma strategy for a global problem.

PMID- 24903782
TI  - The benefits and risks of mathematical modelling in tuberculosis.

PMID- 24903783
TI  - Understanding the costs of better tuberculosis diagnostics.

PMID- 24903785
TI  - Latent tuberculous infection prevalence among paediatric contacts of drug
      resistant and drug-susceptible cases.
AB  - SETTING: Tuberculosis (TB) clinic in Tijuana, Mexico. BACKGROUND: Tuberculin
      conversion rates in contacts of drug-resistant cases have been reported to be
      lower than among contacts of drug-susceptible cases. OBJECTIVE: To determine if
      the prevalence of latent tuberculous infection (LTBI) among paediatric contacts
      of drug-resistant cases is lower than that of contacts of drug-susceptible cases.
      DESIGN: In a cross-sectional study, LTBI among paediatric contacts of culture
      proven TB cases was evaluated using the tuberculin skin test and interferon-gamma
      release assay. Rates among contacts of drug-susceptible and drug-resistant cases
      were compared. RESULTS: The TST was positive in 83.1% of the drug-susceptible
      group vs. 76.0% for the drug-resistant group (P = 0.25). Using the QuantiFERON
      Gold In-Tube (QFT-GIT) assay, drug-resistant cases had a higher rate of
      positivity than the drug-susceptible group, although this difference did not
      reach statistical significance (42.3% positivity among drug-susceptible cases vs.
      57.7% among drug-resistant cases; P = 0.48). CONCLUSIONS: The proportion of LTBI
      is similar among paediatric contacts, regardless of whether the index case is
      drug-resistant or -susceptible.

PMID- 24903786
TI  - High tuberculosis prevalence in children exposed at home to drug-resistant
      tuberculosis.
AB  - SETTING: Urban Karachi, Pakistan. OBJECTIVE: To describe the yield of a contact
      investigation protocol implemented among children living with drug-resistant
      tuberculosis (DR-TB) patients. DESIGN: We implemented a contact investigation
      protocol in households of DR-TB patients treated at the Indus Hospital, Karachi,
      between January 2008 and April 2011. This included a detailed history and
      physical examination, tuberculin skin test, chest radiograph, smear microscopy
      and culture of sputum or gastric aspirate specimens, and drug susceptibility
      testing. Treatment supporters who visited DR-TB patients at home referred all
      child contacts for baseline evaluation and performed monthly assessments. We
      evaluated two age groups: 1) children aged <5 years, and 2) those aged 5-14
      years. RESULTS: Among 133 children aged <15 years in 40 households, 40.4%
      (51/125) were moderately to severely underweight (weight-for-age Z-score <-2).
      Overall, 7.5% (10/133) had TB disease. This proportion was 6.5% (2/31) in those
      aged <5 years and 7.8% (8/102) in those aged 5-14 years. Seven (7/10) were smear
      positive, and 4/10 had culture-confirmed multidrug-resistant Mycobacterium
      tuberculosis CONCLUSION: We detected a high prevalence of TB in children who live
      with DR-TB patients, regardless of the age of the child. Child contacts of DR-TB
      patients are a high-yield population for detecting TB cases.

PMID- 24903784
TI  - How can mathematical models advance tuberculosis control in high HIV prevalence
      settings?
AB  - Existing approaches to tuberculosis (TB) control have been no more than partially
      successful in areas with high human immunodeficiency virus (HIV) prevalence. In
      the context of increasingly constrained resources, mathematical modelling can
      augment understanding and support policy for implementing those strategies that
      are most likely to bring public health and economic benefits. In this paper, we
      present an overview of past and recent contributions of TB modelling in this key
      area, and suggest a way forward through a modelling research agenda that supports
      a more effective response to the TB-HIV epidemic, based on expert discussions at
      a meeting convened by the TB Modelling and Analysis Consortium. The research
      agenda identified high-priority areas for future modelling efforts, including 1)
      the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease
      progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty
      in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV.
      Efficient and rapid progress towards completion of this modelling agenda will
      require co-ordination between the modelling community and key stakeholders,
      including advocates, health policy makers, donors and national or regional
      finance officials. A continuing dialogue will ensure that new results are
      effectively communicated and new policy-relevant questions are addressed swiftly.

PMID- 24903787
TI  - Isoniazid/acetylisoniazid urine concentrations: markers of adherence to isoniazid
      preventive therapy in children.
AB  - The Arkansas colorimetric method monitors adherence to isoniazid (INH) by the
      detection of INH metabolites in urine. Urine samples 4 h after INH administration
      in 31 human immunodeficiency virus infected children receiving daily or thrice
      weekly INH preventive therapy were Arkansas test-positive for 29/31 (94%), while
      acetylisoniazid (AcINH) was detected in 30/31 (97%) using mass spectrometry. At
      24, 48 and 72 h, only 78%, 23% and 0 samples, respectively, were Arkansas
      positive, while INH or AcINH was detected in respectively 94%, 69% and 33%. The
      Arkansas test reliably predicted INH ingestion at a clinic visit 4 h after
      morning doses, but did not perform well at 24 h. 

PMID- 24903788
TI  - Confirming the diagnosis of tuberculosis in children in Northern Portugal.
AB  - Childhood tuberculosis (TB) is difficult to diagnose and there are no
      standardised case definitions. TB records of patients aged >5 years reported in
      Northern Portugal between 2000 and 2009 were reviewed. Of the 116 children
      diagnosed with TB, 72 (62.1%) were male; the mean age was 2.2 +/- 1.2 years. Of
      the 32 children (27.6%) with confirmed TB, only 46.7% had provided samples for
      culture, showing that little effort is made to obtain specimens for confirmation.
      We could not identify independent factors associated with the low rate of sample
      collection or anti-tuberculosis treatment without confirmation; chest radiography
      lesions were less frequent in children who began treatment without confirmation
      (adjusted OR 0.23, 95%CI 0.05-0.98). 

PMID- 24903789
TI  - A home tracing program for contacts of people with tuberculosis or HIV and
      patients lost to care.
AB  - SETTING: Primary care clinic serving a high tuberculosis (TB) and human
      immunodeficiency virus (HIV) prevalence community in South Africa. OBJECTIVE: To
      evaluate a program combining TB and HIV contact investigation with tracing of
      individuals lost to TB or HIV care. DESIGN: Contacts were offered home-based HIV
      testing, TB symptom screening, sputum collection and referral for isoniazid
      preventive therapy (IPT). Effectiveness was assessed by the number needed to
      trace (NNT). RESULTS: Only 419/1197 (35.0%) households were successfully traced.
      Among 267 contacts, we diagnosed 27 new HIV cases (10 linked to care) and two TB
      cases (both initiated treatment) and three started IPT. Of 630 patients lost to
      care, 132 (21.0%) were successfully traced and 81 (61.4%) re-engaged in care. The
      NNT to locate one individual lost to care was 4.8 (95%CI 4.1-5.6), to re-engage
      one person in care 7.8 (95%CI 6.4-9.7), to diagnose one contact with HIV 44.3
      (95%CI 30.6-67.0), to link one newly diagnosed contact to HIV care 120 (95%CI
      65.3-249.2) and to find one contact with active TB and initiate treatment 599
      (95%CI 166.0-4940.7). CONCLUSION: The effectiveness of this contact tracing
      approach in identifying new TB and HIV cases was low. Methods to optimize contact
      investigation should be explored and their cost-effectiveness assessed.

PMID- 24903790
TI  - Is introducing rapid culture into the diagnostic algorithm of smear-negative
      tuberculosis cost-effective?
AB  - SETTING: In 2007, the World Health Organization recommended introducing rapid
      Mycobacterium tuberculosis culture into the diagnostic algorithm of smear
      negative pulmonary tuberculosis (TB). OBJECTIVE: To assess the cost-effectiveness
      of introducing a rapid non-commercial culture method (thin-layer agar), together
      with Lowenstein-Jensen culture to diagnose smear-negative TB at a district
      hospital in Kenya. DESIGN: Outcomes (number of true TB cases treated) were
      obtained from a prospective study evaluating the effectiveness of a clinical and
      radiological algorithm (conventional) against the alternative algorithm
      (conventional plus M. tuberculosis culture) in 380 smear-negative TB suspects.
      The costs of implementing each algorithm were calculated using a 'micro-costing'
      or 'ingredient-based' method. We then compared the cost and effectiveness of
      conventional vs. culture-based algorithms and estimated the incremental cost
      effectiveness ratio. RESULTS: The costs of conventional and culture-based
      algorithms per smear-negative TB suspect were respectively ?39.5 and ?144. The
      costs per confirmed and treated TB case were respectively ?452 and ?913. The
      culture-based algorithm led to diagnosis and treatment of 27 more cases for an
      additional cost of ?1477 per case. CONCLUSION: Despite the increase in patients
      started on treatment thanks to culture, the relatively high cost of a culture
      based algorithm will make it difficult for resource-limited countries to afford.

PMID- 24903791
TI  - Patient costs for the diagnosis of tuberculosis in Brazil: comparison of Xpert
      MTB/RIF and smear microscopy.
AB  - SETTING: Manaus and Rio de Janeiro, two Brazilian state capitals with the
      country's fifth and sixth highest tuberculosis (TB) incidence rates (around
      90/100,000 population in 2012). OBJECTIVE: To compare the costs of the Xpert
      MTB/RIF assay with those of standard care (two smears) in diagnosing TB from the
      patient's perspective. METHOD: We interviewed 218 patients diagnosed with TB in
      the previous 4 months by Xpert or smear microscopy. Information on non-medical
      direct costs for transportation and food, indirect costs such as time spent for
      diagnostic visits and socio-demographic data were gathered. RESULTS: The median
      patient income was US$390.24. Median total costs incurred by patients were 54%
      higher with the smear process than with Xpert (US$25.24 vs. US$16.44, P < 0.000)
      due to higher indirect and direct costs. Male patients incurred higher indirect
      costs (U$10.27 vs. US$7.51, P = 0.038), and patients in Manaus incurred higher
      total costs. CONCLUSIONS: Although the diagnosis and treatment of TB in Brazil
      are free of charge, non-medical direct and indirect costs for patients may
      represent important barriers to accessing appropriate care. Compared to standard
      care, Xpert reduced the financial burden for patients. These findings support the
      decision to scale-up Xpert technology in the country.

PMID- 24903792
TI  - Outbreak of pyrazinamide-monoresistant tuberculosis identified using genotype
      cluster and social media analysis.
AB  - SETTING: Monoresistance to pyrazinamide (PZA) has infrequently been associated
      with Mycobacterium tuberculosis. OBJECTIVE: To report an outbreak of PZA
      monoresistant M. tuberculosis in Virginia involving two genotype clusters from
      December 2004 to August 2010. RESULTS: Thirty cases were identified involving a
      predominantly young, US-born population with histories of substance use and
      incarceration and a large proportion of children aged <15 years (n= 6, 20%); of
      these, 23 cases (77%) were culture-confirmed as M. tuberculosis complex. DNA
      fingerprinting and molecular analysis of the PZA resistance gene, pncA,
      demonstrated a clonal strain that was not M. bovis. Genotypic data provided the
      initial link between seemingly unrelated cases, and helped reveal a historic
      genotype cluster of cases from 2004. Further genotype cluster and contact
      investigation procedures, including the novel use of the social networking
      website Facebook.com, revealed additional links between the 2004 and 2009
      genotype clusters and described an ongoing, extensive outbreak necessitating an
      enhanced screening and treatment protocol for contacts. CONCLUSIONS: This
      outbreak demonstrates how tuberculosis can spread through a young, vulnerable
      population. The use of genotypic data and the novel incorporation of social media
      investigations were critical to understanding the settings and context of
      infectivity.

PMID- 24903793
TI  - Primary drug resistance among pulmonary treatment-naive tuberculosis patients in
      Amazonas State, Brazil.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is the main indicator of
      previous treatment in tuberculosis (TB) patients. MDR-TB among treatment-naive
      patients indicates infection with drug-resistant Mycobacterium tuberculosis
      strains, and such cases are considered primary drug-resistant cases. OBJECTIVE:
      To estimate the prevalence of drug resistance in pulmonary TB (PTB) treatment
      naive patients and to identify the socio-demographic and clinical characteristics
      of the resistant population. METHODS: A total of 205 treatment-naive PTB patients
      from Manaus, Amazonas State, Brazil, were enrolled. Drug susceptibility testing
      (DST) was performed on all positive mycobacterial cultures using the 1%
      proportion method. RESULTS: Positive M. tuberculosis cultures were obtained from
      only 175 patients for DST. The prevalence of primary MDR-TB was 1.7% (3/175);
      14.3% (25/175) of the cultures presented resistance to at least one of the drugs.
      Resistance to streptomycin, isoniazid, rifampicin and ethambutol was respectively
      8.6%, 6.9%, 3.4% and 2.3%. An association between TB patients with resistance to
      more than one drug and known previous household contact with a TB patient was
      observed (P= 0.008, OR 6.7, 95%CI 1.2-67.3). CONCLUSIONS: Although the prevalence
      of primary MDR-TB currently is relatively low, it may become a major public
      health problem if tailored treatment is not provided, as resistance to more than
      one drug is significantly associated with household contact.

PMID- 24903794
TI  - Body mass index predictive of sputum culture conversion among MDR-TB patients in
      Indonesia.
AB  - SETTING: Programmatic management of drug-resistant tuberculosis at Persahabatan
      Hospital, Jakarta, Indonesia. OBJECTIVE: To evaluate the association between body
      mass index (BMI) and sputum culture conversion during treatment for multidrug
      resistant tuberculosis (MDR-TB). DESIGN: We conducted a retrospective cohort
      study of 212 MDR-TB patients. MDR-TB was confirmed using culture in liquid medium
      and line-probe assay. Patients were treated with a standardised regimen unless
      they were resistant to any of the drugs tested. Study outcomes were time to
      culture conversion (primary) and probability of conversion within 4 months
      (secondary). Data were analysed using Kaplan-Meier curves, discrete time-survival
      analysis and Poisson regression. RESULTS: Compared to patients with normal weight
      (BMI >=18.5 kg/m(2)), severely underweight patients (BMI <16 kg/m(2)) had longer
      time to initial conversion (adjusted hazard ratio [aHR] 0.55, 95%CI 0.37-0.84)
      and a lower probability of sputum culture conversion within 4 months (adjusted
      relative risk 0.67, 95%CI 0.54-0.83). Other predictors for longer sputum culture
      conversion were female sex (aHR 0.55, 95%CI 0.39-0.78), resistance to injectables
      (aHR 0.59, 95%CI 0.42-0.83) and high baseline smear grade (aHR 0.33, 95%CI 0.18
      0.60). CONCLUSION: Severe underweight was associated with longer time to initial
      sputum culture conversion among MDR-TB patients.

PMID- 24903796
TI  - Tuberculosis in the intensive care unit: a descriptive analysis in a low-burden
      country.
AB  - BACKGROUND: Although tuberculosis (TB) is not a major public health issue in low
      burden countries, severe cases are still a matter of concern. OBJECTIVE: To
      assess the risk factors for mortality due to TB in a low-burden setting. DESIGN:
      A retrospective study of 97 patients hospitalised with active TB in the intensive
      care unit (ICU) of the Bichat-Claude Bernard Hospital, Paris, France, from 2000
      to 2009. RESULTS: The mean age was 47.4 +/- 14.7 years; 40 patients were human
      immunodeficiency virus (HIV) infected, with a median CD4 cell count of 74
      cells/mm(3). The survival analysis showed that 21 patients died during their time
      in the ICU. The observed risk factors for ICU mortality were organ failure, high
      Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure
      Assessment scores, and concomitant non-tuberculous infection. In multivariate
      analysis, only SAPS II score was significantly associated with mortality.
      CONCLUSION: Risk factors identified in this study are different from those in
      high-burden countries, and were not associated with the site of TB disease. There
      was no difference in TB presentation between HIV-infected and non-HIV-infected
      patients, and HIV was not a mortality risk factor. Low-burden countries still
      experience high death rates due to severe TB.

PMID- 24903795
TI  - Intermittent tuberculosis treatment for patients with isoniazid intolerance or
      drug resistance.
AB  - SETTING: Twenty tuberculosis (TB) clinics in the United States and Canada.
      OBJECTIVE: To evaluate the efficacy and safety of a 6-month intermittent regimen
      of rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB) in human
      immunodeficiency virus (HIV) negative patients with culture-confirmed pulmonary
      or extra-pulmonary tuberculosis and either isoniazid (INH) resistance or INH
      intolerance. DESIGN: Patients were enrolled in a single-arm clinical trial to
      receive intermittent dosing after at least 14 initial daily doses of RMP+PZA+EMB.
      Treatment was continued twice (BIW) or thrice weekly (TIW) per physician/patient
      preference for a total of 6 months, with 2 years of follow-up for relapse after
      treatment. RESULTS: From 1999 to 2004, 98 patients were enrolled, 78 with
      reported INH resistance and 20 with INH intolerance. BIW dosing was used in 77
      and TIW in 21. Study treatment was completed in 73 (74%). Reasons for
      discontinuation were hepatic adverse events (n= 12), other adverse effects (n= 3)
      and other reasons (n= 10). Failure (n= 1) and relapse (n= 2) occurred in 3 (3.5%,
      95%CI 1.2-9.8) of 86 patients eligible for efficacy analysis, all occurring in
      patients with cavitary, acid-fast bacilli smear-positive pulmonary TB.
      CONCLUSIONS: Intermittent RMP+PZA+EMB appears to be effective in HIV-negative
      patients, but the regimen is poorly tolerated, possibly due to the prolonged use
      of PZA. Alternative regimens of lower toxicity are needed.

PMID- 24903797
TI  - Genetic polymorphisms of CYP2E1 and GSTM1 loci and susceptibility to anti
      tuberculosis drug-induced hepatotoxicity.
AB  - BACKGROUND: Host genetic factors that influence predisposition to anti
      tuberculosis drug-induced hepatotoxicity (DIH) are not clear in the Indian
      population. OBJECTIVE: To investigate the possible association of DIH with
      polymorphism at the RsaI site of the 5-prime untranslated region of CYP2E1 and
      GSTM1 'null' mutations. METHODS: In this prospective study, 113 tuberculosis (TB)
      patients with DIH and 201 TB patients receiving anti-tuberculosis treatment
      without developing hepatotoxicity (non-DIH) constituted cases and controls,
      respectively. Polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) was performed to analyse genetic polymorphisms of CYP450 2E1 at the
      RsaI site and 'null' GSTM1 mutations. PCR-RFLP results were compared between 185
      non-DIH and 105 DIH patients RESULTS: A high frequency of c1c1 genotypes of
      CYP2E1 was commonly encountered, and the difference between DIH and non-DIH
      patients was not significant (75.14% vs. 77.14%). The genotypic distribution of
      c2c2 was significantly higher in the DIH than in the non-DIH group (4.8% vs.
      0.5%, OR 8.58, P = 0.03). However, adjustment for age, sex and serum albumin
      differences yielded an OR of 2.75, making it non-significant (P = 0.26).
      Homozygous 'null' mutation frequencies at the GSTM1 gene in DIH and non-DIH
      patients were observed that were not significantly different (40% and 37%,
      respectively, P = 0.61). CONCLUSION: RsaI variants of the CYP2E1 gene and GSTM1
      'null' mutation were not associated with risk of DIH in a north Indian
      population.

PMID- 24903798
TI  - Second worldwide proficiency study on variable number of tandem repeats typing of
      Mycobacterium tuberculosis complex.
AB  - BACKGROUND: The quality of variable number of tandem repeats (VNTR) typing of
      Mycobacterium tuberculosis was first investigated in 2009 in 37 laboratories
      worldwide. The results revealed an inter- and intra-laboratory reproducibility of
      respectively 60% and 72%. These data spurred an improvement in laboratory
      specific assays and global standardisation of VNTR typing. OBJECTIVE: To measure
      the effects of the technical improvements and increased standardisation, a test
      panel consisting of 30 M. tuberculosis complex DNA samples was distributed for
      VNTR typing in 41 participating laboratories from 36 countries. RESULTS: The
      inter- and intra-laboratory reproducibility increased overall to respectively 78%
      and 88%. The 33 laboratories that participated in both the first and second
      proficiency studies improved their inter- and intra-laboratory reproducibility
      from 62% and 72% to respectively 79% and 88%. The largest improvement in
      reproducibility was detected in 10 laboratories that use an in-house polymerase
      chain reaction technique and perform amplicon sizing using gel electrophoresis.
      Detailed error analysis revealed a reduction in the number of systematic errors,
      sample exchange events and non-amplifiable loci. CONCLUSION: This second
      worldwide proficiency study indicates a substantial increase in the
      reproducibility of VNTR typing of M. tuberculosis. This will contribute to a more
      meaningful interpretation of molecular epidemiological and phylogenetic studies
      on the M. tuberculosis complex.

PMID- 24903799
TI  - Serum concentrations of cycloserine and outcome of multidrug-resistant
      tuberculosis in Northern Taiwan.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) has been advocated to promote the
      efficacy of anti-tuberculosis agents. Cycloserine (CS) is a second-line anti
      tuberculosis drug whose serum concentrations in tuberculosis (TB) patients are
      largely unknown. OBJECTIVES: To investigate serum CS concentrations after drug
      ingestion in TB patients. METHODS: Multidrug-resistant TB patients who were
      taking CS in a tertiary care centre in northern Taiwan between 1 April 2009 and
      31 October 2009 were enrolled in the study. Serum CS concentrations were measured
      at 2 and 6 h after drug administration. RESULTS: Of 32 patients enrolled, 23 were
      males and 9 females. The mean CS dose was 8.8 +/- 1.3 mg/kg. The mean serum
      concentrations at 2 and 6 h were respectively 19.7 +/- 8.3 and 18.1 +/- 8.7
      MUg/ml. Seven patients (22%) had serum drug concentrations that were higher at 6
      h than at 2 h, 12 (38%) had peak serum concentrations within the recommended
      range of 20-35 MUg/ml; 18 patients (56%) had concentrations <20 MUg/ml at both 2
      h and 6 h; and 2 patients (6%) had at least one measurement >35 MUg/ml.
      CONCLUSION: Lower than recommended serum CS concentrations and delayed absorption
      were common. It is essential to develop practical TDM to maintain proper serum
      drug concentrations.

PMID- 24903800
TI  - Impact of routine sputum cytology in a population at high risk for bronchial
      carcinoma.
AB  - SETTING: Sub-Saharan Africa carries a high burden of lung cancer, with limited
      access to specialised health care. OBJECTIVE: To investigate the diagnostic value
      of sputum cytology and its potential in reducing the need for invasive diagnostic
      procedures in a high-risk population. DESIGN: We collected spontaneously
      expectorated sputum from 108 patients referred for a diagnostic procedure for
      suspected lung cancer between June 2010 and June 2012, and examined the
      diagnostic yield of sputum cytology for malignant cells as well as factors
      predicting a positive result. RESULTS: Bronchial carcinoma was diagnosed in 90
      patients (83.3%), of whom 35 (38.9%) had sputum cytology positive for malignant
      cells with 100% diagnostic accuracy. Positive sputum cytology was significantly
      associated with endobronchial tumour and obstruction seen during bronchoscopy (OR
      4.69 and OR 8.89, respectively), and with a histology of squamous cell carcinoma
      (OR 1.9). All but one patient with positive sputum were inoperable (97.1%), and
      we estimated that up to a third of all invasive procedures could be avoided if
      sputum cytology was used for triage. CONCLUSION: Sputum cytology had a high yield
      and accuracy in this high-risk group. Its routine use in selected patients is
      likely to result in reduced costs and less patient risk and discomfort.

PMID- 24903801
TI  - Indoor air pollution from solid fuel and tuberculosis: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To conduct an updated systematic review and meta-analysis on the
      association between indoor air pollution and tuberculosis (TB). DESIGN: We
      searched for English or Chinese articles using PubMed and EMBASE up to 28
      February 2013. We aimed to identify randomised controlled trials and
      observational epidemiological studies that reported the association between
      domestic use of solid fuel and TB. Two reviewers independently extracted the
      information from included studies and assessed the risk of bias of these studies
      using pre-defined criteria. The effect sizes of eligible studies were pooled
      using a random-effects model; the heterogeneity across studies was quantified
      using I(2) statistics. RESULTS: We identified 15 studies on solid fuel use and
      active TB and one on solid fuel use and latent tuberculous infection. The summary
      odds ratios from case-control and cross-sectional studies were respectively 1.17
      (95%CI 0.83 - 1.65) and 1.62 (95%CI 0.89 - 2.93), with substantial between-study
      heterogeneity (I(2) 56.2% and 80.5%, respectively). Subgroup analysis and meta
      regression analysis did not identify any study-level factors that could explain
      the heterogeneity observed. CONCLUSION: The level of evidence for the association
      between domestic use of solid fuels and TB was very low. High-quality studies are
      badly needed to clarify this association and to estimate the magnitude of the
      problem.

PMID- 24903802
TI  - Dose-related effect of urinary cotinine levels on pulmonary function among Korean
      women.
AB  - SETTING: Country-wide general population in South Korea. BACKGROUND: The dose
      response relationship between smoking and pulmonary function in women may have
      been significantly over-estimated by studies that employed a self-reporting
      questionnaire. OBJECTIVE: To evaluate whether this relationship was still
      observed among Korean women when smoking levels were determined by urinary
      cotinine measurements. DESIGN: A total of 4584 Korean women from the spirometry
      data set of the Korean National Health and Nutrition Examination Surveys IV and V
      (2008-2010) were included. Analysis of covariance was performed to estimate the
      dose-related effect of urinary cotinine levels on pulmonary function after
      adjusting for covariates in this country-wide cross-sectional study. RESULTS:
      Compared to urinary cotinine levels (cut-off 50 ng/ml), the false-positive rate
      of self-reported smoking was 53.2%. After the smokers were divided into deciles,
      the regression coefficients for percentage forced expiratory volume in 1 second
      (FEV1%) and percentage forced expiratory volume/forced volume capacity (FEV1/FVC)
      ratio (FEV1/FVC%) were -0.2903 and -0.2680 (%/decile), respectively (both P <
      0.001). CONCLUSION: It is necessary to use objective methods when determining the
      smoking status of Korean women. Even after reducing information bias, smoking
      affected pulmonary function in a dose-dependent manner.

PMID- 24903803
TI  - Fluoroquinolone resistance and Mycobacterium tuberculosis: CAP guidelines play an
      important role.

PMID- 24903804
TI  - Relapsing neuromyelitis optica temporally related to recurrent pulmonary
      tuberculosis.

PMID- 24903805
TI  - Predator-prey imbalances due to a pesticide: density and applicability timing as
      determining factors for experimental assessments.
AB  - Predator-prey relationships are determining factors in sustaining community
      structure but xenobiotics, including pesticides, have the potential to alter
      them, causing imbalances at the ecosystem level. Although invertebrate predation
      on zooplankton is of high importance in shallow lakes, there is still little
      information regarding disturbances on this trophic interaction. This work
      assessed the potential effects of a chlorpyrifos-based pesticide (CLP) on the
      interaction between prawns Macrobrachium borellii and cladocerans Ceriodaphnia
      dubia, taking into account prey densities, specific time of exposure and
      contamination level. The analysis was focused on the specific sensitivity of both
      species and, especially, on the predation rate of M. borellii on C. dubia. The
      latter was evaluated through different treatments that combined predator and/or
      prey exposure to the insecticide, before (lapse of 12 h) or during the
      interaction. Under low prey density, when prawns were previously exposed to the
      insecticide, their consumption rate was lower than that of controls. Conversely,
      when cladocerans or both species were previously exposed, the prawns' feeding
      rate was higher. Under high prey density, there were no substantial differences
      among treatments. Comparatively, cladocerans were significantly more consumed
      when the exposure of both species was performed before rather than during the
      interaction. From the results obtained, it can be assumed that the trophic
      interaction under study is sensitive to CLP and that individual density and
      specific time of exposure are important variables to be considered in similar
      studies in order to obtain realistic results.

PMID- 24903806
TI  - Chemical properties and toxicity of soils contaminated by mining activity.
AB  - This research is aimed at assessing the total content and soluble forms of metals
      (zinc, lead and cadmium) and toxicity of soils subjected to strong human pressure
      associated with mining of zinc and lead ores. The research area lay in the
      neighbourhood of the Boleslaw Mine and Metallurgical Plant in Bukowno (Poland).
      The study obtained total cadmium concentration between 0.29 and 51.91 mg, zinc
      between 7.90 and 3,614 mg, and that of lead between 28.4 and 6844 mg kg(-1) of
      soil d.m. The solubility of the heavy metals in 1 mol dm(-3) NH4NO3 was 1-49% for
      zinc, 5-45% for cadmium, and <1-10% for lead. In 1 mol HCl dm(-3), the solubility
      of the studied metals was much higher and obtained values depending on the
      collection site, from 45 to 92% for zinc, from 74 to 99%, and from 79 to 99% for
      lead. The lower solubility of the heavy metals in 1 mol dm(-3) NH4NO3 than 1 mol
      HCl dm(-3) is connected with that, the ammonium nitrate has low extraction power,
      and it is used in determining the bioavailable (active) form of heavy metals.
      Toxicity assessment of the soil samples was performed using two tests,
      Phytotoxkit and Microtox((r)). Germination index values were between 22 and 75%
      for Sinapis alba, between 28 and 100% for Lepidium sativum, and between 10 and
      28% for Sorghum saccharatum. Depending on the studied soil sample, Vibrio
      fischeri luminescence inhibition was 20-96%. The sensitivity of the test
      organisms formed the following series: S. saccharatum > S. alba = V. fischeri >
      L. sativum. Significant positive correlations (p <= 0.05) of the total and
      soluble contents of the metals with luminescence inhibition in V. fischeri and
      root growth inhibition in S. saccharatum were found. The general trend observed
      was an increase in metal toxicity measured by the biotest with increasing
      available metal contents in soils. All the soil samples were classified into
      toxicity class III, which means that they are toxic and present severe danger.
      Biotest are a good complement to chemical analyses in the assessment of quality
      of soils as well as in properly managing them.

PMID- 24903808
TI  - Explosive synchronization as a process of explosive percolation in dynamical
      phase space.
AB  - Explosive synchronization and explosive percolation are currently two independent
      phenomena occurring in complex networks, where the former takes place in
      dynamical phase space while the latter in configuration space. It has been
      revealed that the mechanism of EP can be explained by the Achlioptas process,
      where the formation of a giant component is controlled by a suppressive rule. We
      here introduce an equivalent suppressive rule for ES. Before the critical point
      of ES, the suppressive rule induces the presence of multiple, small sized,
      synchronized clusters, while inducing the abrupt formation of a giant cluster of
      synchronized oscillators at the critical coupling strength. We also show how the
      explosive character of ES degrades into a second-order phase transition when the
      suppressive rule is broken. These results suggest that our suppressive rule can
      be considered as a dynamical counterpart of the Achlioptas process, indicating
      that ES and EP can be unified into a same framework. 

PMID- 24903807
TI  - Association between different obesity measures and the risk of stroke in the EPIC
      Spanish cohort.
AB  - INTRODUCTION: There is still a scientific debate on the exact role played by
      obesity on stroke risk. OBJECTIVE: The aim of the study was to analyze the
      association between obesity, measured by different indices such as body mass
      index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and a new one
      called A Body Shape Index (ABSI) and the risk of total and ischemic stroke.
      SUBJECTS/METHODS: A total of 41,020 subjects (15,490 men and 25,530 women) aged
      29-69 years participated in the study. All participants were recruited between
      1992 and 1996 and followed up until 2008 to ascertain incident cerebrovascular
      disease events. Cox proportional hazards models were designed to estimate the
      relative risk and 95% CI between obesity and cerebrovascular disease incidence.
      RESULTS: After 13.8 years of follow-up, a total of 674 stroke cases (55.3% in
      men) were registered (531 ischemic, 79 hemorrhagic, 42 subarachnoid hemorrhage
      and 22 unspecified). WC fourth quartile (HR 1.95; 95% CI 1.20-3.19) and WHR
      fourth quartile (HR 1.58; 95% CI 1.12-2.25) were positively associated with total
      stroke only in men. BMI was not associated with stroke incidence. The new index,
      ABSI, was significantly associated with total stroke incidence only in men (HR
      1.54; 95% CI 1.06-2.23). CONCLUSIONS: Data from the Spanish EPIC cohort study
      show a strong association of WC and WHR with the relative risk of suffering a
      stroke only in men, while no associations were found for BMI. It supports the
      suggestion of other authors of using more than one obesity index in the study of
      stroke risk prediction.

PMID- 24903809
TI  - Post-production modification of industrial enzymes.
AB  - Industry has an increasing interest in the use of enzymes as environmentally
      friendly, highly efficient, and specific bio-catalysts. Enzymes have primarily
      evolved to function in aqueous environments at ambient temperature and pressure.
      These conditions however do not always correspond with industrial processes or
      applications, and only a small portion of all known enzymes are therefore
      suitable for industrial use. Protein engineering can sometimes be applied to
      convey more desirable properties to enzymes, such as increased stability, but is
      limited to the 20 naturally occurring amino acids or homologs thereof. Using post
      production modification, which has the potential to combine desirable properties
      from the enzyme and the conjugated compounds, enzymes can be modified with both
      natural and synthetic molecules. This offers access to a myriad of possibilities
      for tuning the properties of enzymes. At this moment, however, the effects of
      post-production modification cannot yet be reliably predicted. The increasing
      number of applications will improve this so that the potential of this technology
      can be fully exploited. This review will focus on post-production modification of
      enzymes and its use and opportunities in industry. 

PMID- 24903810
TI  - Short-term effect of acetate and ethanol on methane formation in biogas sludge.
AB  - Biochemical processes in biogas plants are still not fully understood.
      Especially, the identification of possible bottlenecks in the complex
      fermentation processes during biogas production might provide potential to
      increase the performance of biogas plants. To shed light on the question which
      group of organism constitutes the limiting factor in the anaerobic breakdown of
      organic material, biogas sludge from different mesophilic biogas plants was
      examined under various conditions. Therefore, biogas sludge was incubated and
      analyzed in anaerobic serum flasks under an atmosphere of N2/CO2. The batch
      reactors mirrored the conditions and the performance of the full-scale biogas
      plants and were suitable test systems for a period of 24 h. Methane production
      rates were compared after supplementation with substrates for syntrophic
      bacteria, such as butyrate, propionate, or ethanol, as well as with acetate and
      H2+CO2 as substrates for methanogenic archaea. Methane formation rates increased
      significantly by 35 to 126 % when sludge from different biogas plants was
      supplemented with acetate or ethanol. The stability of important process
      parameters such as concentration of volatile fatty acids and pH indicate that
      ethanol and acetate increase biogas formation without affecting normally
      occurring fermentation processes. In contrast to ethanol or acetate, other
      fermentation products such as propionate, butyrate, or H2 did not result in
      increased methane formation rates. These results provide evidence that
      aceticlastic methanogenesis and ethanol-oxidizing syntrophic bacteria are not the
      limiting factor during biogas formation, respectively, and that biogas plant
      optimization is possible with special focus on methanogenesis from acetate. 

PMID- 24903811
TI  - A contribution to set a legal framework for biofertilisers.
AB  - The extensive research, production and use of microorganisms to improve plant
      nutrition have resulted in an inconsistent definition of the term "biofertiliser"
      which, in some cases, is due to the different microbial mechanisms involved. The
      rationale for adopting the term biofertiliser is that it derives from "biological
      fertiliser", that, in turn, implies the use of living microorganisms. Here, we
      propose a definition for this kind of products which is distinguishing them from
      biostimulants or other inorganic and organic fertilisers. Special emphasis is
      given to microorganism(s) with multifunctional properties and biofertilisers
      containing more than one microorganism. This definition could be included in
      legal provisions regulating registration and marketing requirements. A set of
      rules is also proposed which could guarantee the quality of biofertilisers
      present on the market and thus foster their use by farmers. 

PMID- 24903812
TI  - Probiotic abilities of riboflavin-overproducing Lactobacillus strains: a novel
      promising application of probiotics.
AB  - The probiotic potential of Lactobacillus plantarum and Lactobacillus fermentum
      strains, capable of overproducing riboflavin, was investigated. The riboflavin
      production was quantified in co-cultures of lactobacilli and human intestinal
      epithelial cells, and the riboflavin overproduction ability was confirmed. When
      milk and yogurt were used as carrier matrices, L. plantarum and L. fermentum
      strains displayed a significant ability to survive through simulated
      gastrointestinal transit. Adhesion was studied on both biotic and abiotic
      surfaces. Both strains adhered strongly on Caco-2 cells, negatively influenced
      the adhesion of Escherichia coli O157:H7, and strongly inhibited the growth of
      three reference pathogenic microbial strains. Resistance to major antibiotics and
      potential hemolytic activity were assayed. Overall, this study reveals that these
      Lactobacillus stains are endowed with promising probiotic properties and thus are
      candidates for the development of novel functional food which would be both
      enriched in riboflavin and induce additional health benefits, including a
      potential in situ riboflavin production, once the microorganisms colonize the
      host intestine. 

PMID- 24903813
TI  - Souring in low-temperature surface facilities of two high-temperature Argentinian
      oil fields.
AB  - Produced waters from the Barrancas and Chihuido de la Salina (CHLS) fields in
      Argentina had higher concentrations of sulfate than were found in the injection
      waters, suggesting that the formation waters in these reservoirs had a high
      sulfate concentration and that sulfate-reducing bacteria were inactive downhole.
      Incubation of produced waters with produced oil gave rapid reduction of sulfate
      to sulfide (souring) at 37  degrees C, some at 60  degrees C, but none at 80 
      degrees C. Alkylbenzenes and alkanes served as electron donor, especially in
      incubations with CHLS oil. Dilution with water to decrease the ionic strength or
      addition of inorganic phosphate did not increase souring at 37 or 60  degrees C.
      These results indicate that souring in these reservoirs is limited by the
      reservoir temperature (80  degrees C for the Barrancas and 65-70  degrees C for
      the CHLS field) and that souring may accelerate in surface facilities where the
      oil-water mixture cools. As a result, significant sulfide concentrations are
      present in these surface facilities. The activity and presence of
      chemolithotrophic Gammaproteobacteria of the genus Thiomicrospira, which
      represented 85% of the microbial community in a water plant in the Barrancas
      field, indicated reoxidation of sulfide and sulfur to sulfate. The presence of
      these bacteria offers potential for souring control by microbial oxidation in
      aboveground facilities, provided that formation of corrosive sulfur can be
      avoided.

PMID- 24903814
TI  - Persistence of antibiotic-resistant and -sensitive Proteus mirabilis strains in
      the digestive tract of the housefly (Musca domestica) and green bottle flies
      (Calliphoridae).
AB  - Synanthropic flies have been implicated in the rapid dissemination of antibiotic
      resistant bacteria and resistance determinants in the biosphere. These flies
      stably harbor a considerable number of bacteria that exhibit resistance to
      various antibiotics, but the mechanisms underlying this phenomenon remain
      unclear. In this study, we investigated the persistence of antibiotic-resistant
      bacteria in the digestive tract of houseflies and green bottle flies, using
      Proteus mirabilis as a model microorganism. One resistant strain carried the
      blaTEM and aphA1 genes, and another carried a plasmid containing qnrD gene.
      Quantitative PCR and 454 pyrosequencing were used to monitor the relative
      abundance of the Proteus strains, as well as potential changes in the overall
      structure of the whole bacterial community incurred by the artificial induction
      of Proteus cultures. Both antibiotic-resistant and -sensitive P. mirabilis
      strains persisted in the fly digestive tract for at least 3 days, and there was
      no significant difference in the relative abundance of resistant and sensitive
      strains despite the lower growth rate of resistant strains when cultured in
      vitro. Therefore, conditions in the fly digestive tract may allow resistant
      strains to survive the competition with sensitive strains in the absence of
      antibiotic selective pressure. The composition of the fly-associated bacterial
      community changed over time, but the contribution of the artificially introduced
      P. mirabilis strains to these changes was not clear. In order to explain these
      changes, it will be necessary to obtain more information about bacterial
      interspecies antagonism in the fly digestive tract.

PMID- 24903815
TI  - Copper tolerance in Frankia sp. strain EuI1c involves surface binding and copper
      transport.
AB  - Several Frankia strains have been shown to be copper-tolerant. The mechanism of
      their copper tolerance was investigated for Frankia sp. strain EuI1c. Copper
      binding was shown by binding studies. Unusual globular structures were observed
      on the surface of the bacterium. These globular structures were composed of
      aggregates containing many relatively smaller "leaf-like" structures. Scanning
      electron microscopy with energy-dispersive X-ray (SEM-EDAX) analysis of these
      structures indicated elevated copper and phosphate levels compared to the control
      cells. Fourier transform infrared spectroscopy (FTIR) analysis indicated an
      increase in extracellular phosphate on the cell surface of copper-stressed cells.
      Bioinformatics' analysis of the Frankia sp. strain EuI1c genome revealed five
      potential cop genes: copA, copZ, copC, copCD, and copD. Experiments with Frankia
      sp. strain EuI1c using qRT-PCR indicated an increase in messenger RNA (mRNA)
      levels of the five cop genes upon Cu(2+) stress. After 5 days of Cu(2+) stress,
      the copA, copZ, copC, copCD, and copD mRNA levels increased 25-, 8-, 18-, 18-,
      and 25-fold, respectively. The protein profile of Cu(2+)-stressed Frankia sp.
      strain EuI1c cells revealed the upregulation of a 36.7 kDa protein that was
      identified as FraEuI1c_1092 (sulfate-binding periplasmic transport protein).
      Homologues of this gene were only present in the genomes of the Cu(2+)-resistant
      Frankia strains (EuI1c, DC12, and CN3). These data indicate that copper tolerance
      by Frankia sp. strain EuI1c involved the binding of copper to the cell surface
      and transport proteins. 

PMID- 24903816
TI  - Combination of heterogeneous catalase and superoxide dismutase protects
      Bifidobacterium longum strain NCC2705 from oxidative stress.
AB  - Bifidobacteria are generally sensitive to oxidative stress caused by reactive
      oxygen species (ROS). To improve oxidative-stress tolerance, the superoxide
      dismutase (SOD) gene from Streptococcus thermophilus (StSodA) and the heme
      dependent catalase (KAT) gene from Lactobacillus plantarum (LpKatL) were
      heterologously expressed in Bifidobacterium longum strain NCC2705. Three types of
      strain NCC2705 transformants were obtained: with transgenic SOD expression, with
      transgenic KAT expression, and with coexpression of the two genes. Intracellular
      expression of the genes and their functional role in oxidative-stress resistance
      were evaluated. In response to oxidative stress, B. longum NCC2705/pDP401-LpKatL
      (expressing LpKatL) and NCC2705/pDP-Kat-Sod (coexpressing LpKatL and StSodA)
      rapidly degraded exogenous H2O2 and the peroxides generated as a byproduct of
      aerobic cultivation, preventing oxidative damage to DNA and RNA. Individual
      expression of StSodA or LpKatL both improved B. longum NCC2705 cell viability.
      Survival rate of strain NCC2705 was further improved by combining SOD and KAT
      expression. The two enzymes played complementary roles in ROS-scavenging
      pathways, and coexpression led to a synergistic beneficial effect under
      conditions of intensified oxidative stress. Our results illustrate that
      heterogeneous expression of heme-dependent KAT and Mn(2+)-dependent SOD is
      functional in the B. longum oxidative-stress response, and synergistic protection
      is achieved when their expressions are combined.

PMID- 24903817
TI  - Primary study on the lesions and specific proteins in BEAS-2B cells induced with
      the 2009 A (H1N1) influenza virus.
AB  - In order to investigate the lesions and proteins with differential expression in
      cells infected with the 2009 A (H1N1) virus and to determine the specific
      proteins involved in cell damage, the present study has been performed. BEAS-2B
      cells were infected with the 2009 A (H1N1) influenza virus or the seasonal H1N1
      influenza virus for 12, 24, 48, and 72 h, and cell cycle and apoptosis were
      analyzed with flow cytometry. Total cellular proteins were extracted and
      underwent two-dimensional gel electrophoresis. The differentially expressed
      proteins underwent mass spectrometry for identification. The results showed that
      after 12 h, cells infected with the virus strain sourced from severe cases had
      the highest apoptosis rate (P < 0.05). After 48 h, cells infected with the virus
      strain sourced from fatal cases and severe cases had the highest apoptosis rate
      (P < 0.05), and after 72 h, cells infected with virus strains from fatal cases
      and ordinary cases had the highest apoptosis rate (P < 0.05). All the four
      influenza virus strains induced cell cycle arrest mainly at the G0/G1 phase.
      Eighteen differentially expressed proteins were identified, including galectin-1,
      cofilin-1, protein DJ-1, proteasome subunit alpha type-5, macrophage migration
      inhibitory factor, translationally controlled tumor protein, profilin 1, and
      interferon alpha-2. Galectin-1 was specifically observed in BEAS-2B infected with
      2009 A (H1N1) influenza viruses, and cofilin-1 was specifically observed in BEAS
      2B cells in the late stage of 2009 A (H1N1) influenza virus infection. In
      conclusion, differential effects of the 2009 A (H1N1) influenza virus and
      seasonal H1N1 influenza virus were identified on the cell cycle and apoptosis,
      and galectin-1 may play a role in cell apoptosis induced by 2009 A (H1N1)
      influenza virus.

PMID- 24903818
TI  - Improved PCR assay for the specific detection and quantitation of Escherichia
      coli serotype O157 in water.
AB  - Escherichia coli serotype O157 is still a major global healthcare problem.
      However, only limited information is now available on the molecular and
      serological detection of pathogenic bacteria. Therefore, the development of
      appropriate strategies for their rapid identification and monitoring is still
      needed. In general, the sequence analysis based on stx, slt, eae, hlyA, rfb, and
      fliCh7 genes is widely employed for the identification of E. coli serotype O157;
      but there have been critical defects in the diagnosis and identification of E.
      coli serotype O157, in that they are also present in other E. coli serogroups. In
      this study, NCBI-BLAST searches using the nucleotide sequences of the putative
      regulatory protein gene from E. coli O157:H7 str. Sakai found sequence difference
      at the serotype level. The specific primers from the putative regulatory protein
      gene were designed and investigated for their sensitivity and specificity for
      detecting the pathogen in environment water samples. The specificity of the
      primer set was evaluated using genomic DNA from 8 isolates of E. coli serotype
      O157 and 32 other reference strains. In addition, the sensitivity and specificity
      of this assay were confirmed by successful identification of E. coli serotype
      O157 in environmental water samples. In conclusion, this study showed that the
      newly developed quantitative serotype-specific PCR method is a highly specific
      and efficient tool for the surveillance and rapid detection of high-risk E. coli
      serotype O157.

PMID- 24903820
TI  - Major General Norman T. Kirk and amputee care during World War II.

PMID- 24903819
TI  - People awakening: collaborative research to develop cultural strategies for
      prevention in community intervention.
AB  - The consequences of alcohol use disorder (AUD) and suicide create immense health
      disparities among Alaska Native people. The People Awakening project is a long
      term collaboration between Alaska Native (AN) communities and university
      researchers seeking to foster health equity through development of positive
      solutions to these disparities. These efforts initiated a research relationship
      that identified individual, family, and community protective factors from AUD and
      suicide. AN co-researchers next expressed interest in translating these findings
      into intervention. This led to development of a strengths-based community
      intervention that is the focus of the special issue. The intervention builds
      these protective factors to prevent AUD and suicide risk within AN youth, and
      their families and communities. This review provides a critical examination of
      existing literature and a brief history of work leading to the intervention
      research. These work efforts portray a shared commitment of university
      researchers and community members to function as co-researchers, and to conduct
      research in accord with local Yup'ik cultural values. This imperative allowed the
      team to navigate several tensions we locate in a convergence of historical and
      contemporary ecological contextual factors inherent in AN tribal communities with
      countervailing constraints imposed by Western science. 

PMID- 24903822
TI  - Editor's Spotlight/Take 5: Hospital readmissions after treatment of proximal
      humerus fractures: is arthroplasty safer than open reduction internal fixation?

PMID- 24903823
TI  - New total knee arthroplasty designs: do young patients notice?
AB  - BACKGROUND: Although the volume of total knee arthroplasties (TKAs) performed in
      the United States continues to increase, recent reports have shown the percentage
      of patients who remain "unsatisfied" is as high as 15% to 30%. Recently, several
      newer implant designs have been developed to potentially improve patient
      outcomes. QUESTIONS/PURPOSES: The purpose of this study was to determine the
      impact of high-flex, gender-specific, and rotating-platform TKA designs on
      patient satisfaction and functional outcomes. METHODS: A four-center study was
      designed to quantify the degree of residual symptoms and functional deficits in
      patients undergoing TKA with newer implant designs compared with a 10-year-old,
      cruciate-retaining (CR) TKA system introduced in 2003. Each contributing surgeon
      was fellowship-trained and specialized in joint replacement surgery. Only
      patients younger than 60 years old were included. Data were collected by an
      independent, third-party survey center blinded to the implant type, who
      administered questionnaires about patient satisfaction, residual symptoms,
      function, and pre- and postoperative activity levels using previously published
      survey instruments. Two hundred thirty-seven CR, 137 rotating-platform, 88 gender
      specific, and 65 high-flex TKAs were included in the analysis. Differences in
      baseline demographic variables were accounted for using multiple logistic
      regression statistical analyses. RESULTS: Patients who received certain newer
      designs reported more residual symptoms (grinding, popping, and clicking) in the
      30 days before survey administration than the group receiving a 10-year-old CR
      design (CR, 24% [57 of 237 patients] versus gender-specific, 36% [32 of 88
      patients]; odds ratio [OR], 2.1; 95% confidence interval [CI], 1.1-3.8; p=0.03;
      and rotating-platform, 43% [59 of 137 patients]; OR, 2.2; 95% CI, 1.3-3.7;
      p<0.001). They also reported more functional problems, including getting in and
      out of a chair (CR, 19% [46 of 237 patients] versus gender-specific, 37% [32 of
      88 patients]; OR, 1.0; 95% CI, 1.1-3.5; p=0.001). Patients with newer TKA designs
      did not demonstrate any improvements in function or patient satisfaction versus
      those who received the 10-year-old CR design. CONCLUSIONS: When interviewed by an
      independent, blinded third party, the use of newer implant designs did not
      improve patient satisfaction and the presence of residual symptoms when compared
      with patients who received the 10-year-old CR design. Future studies should
      prospectively determine whether the purported benefits of newer implant designs
      improve patient-perceived outcomes. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 24903824
TI  - Obesity does not affect survival outcomes in extremity soft tissue sarcoma.
AB  - BACKGROUND: Obesity is a growing epidemic and has been associated with an
      increased frequency of complications after various surgical procedures. Studies
      also have shown adipose tissue to promote a microenvironment favorable for tumor
      growth. Additionally, the relationship between obesity and prognosis of soft
      tissue sarcomas has yet to be evaluated. QUESTIONS/PURPOSES: We sought to assess
      if (1) obesity affects survival outcomes (local recurrence, distant metastasis,
      and death attributable to disease) in patients with extremity soft tissue
      sarcomas; and (2) whether obesity affected wound healing and other surgical
      complications after treatment. METHODS: A BMI of 30 kg/m(2) or greater was used
      to define obesity. Querying our prospective database between 2001 and 2008, we
      identified 397 patients for the study; 154 were obese and 243 were not obese.
      Mean followup was 4.5 years (SD, 3.1 years) in the obese group and 3.9 years (SD,
      3.2 years) in the nonobese group; the group with a BMI of 30 kg/m(2) or greater
      had a higher proportion of patients with followups of at least 2 years compared
      with the group with a BMI less than 30 kg/m(2) (76% versus 62%). Outcomes,
      including local recurrence, distant metastasis, and overall survival, were
      analyzed after patients were stratified by BMI. Multivariable survival models
      were used to identify independent predictors of survival outcomes. Wilcoxon rank
      sum test was used to compare continuous variables. Based on the accrual interval
      of 8 years, the additional followup of 5 years after data collection, and the
      median survival time for the patients with a BMI less than 30 kg/m(2) of 3 years,
      we were able to detect true median survival times in the patients with a BMI of
      30 kg/m(2) of 2.2 years or less with 80% power and type I error rate of 0.05.
      RESULTS: Patients who were obese had similar survival outcomes and wound
      complication rates when compared with their nonobese counterparts. Patients who
      were obese were more likely to have lower-grade tumors (31% versus 20%; p =
      0.021) and additional comorbidities including diabetes mellitus (26% versus 7%; p
      < 0.001), hypertension (63% versus 38%; p < 0.001), and smoking (49% versus 37%;
      p = 0.027). Regression analysis confirmed that even after accounting for certain
      tumor characteristics and comorbidities, obesity did not serve as an independent
      risk factor in affecting survival outcomes. CONCLUSIONS: Although the prevalence
      of obesity continues to increase and lead to many negative health consequences,
      it does not appear to adversely affect survival, local recurrence, or wound
      complication rates for patients with extremity soft tissue sarcomas. LEVEL OF
      EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24903825
TI  - Toward neurobiological characterization of functional homogeneity in the human
      cortex: regional variation, morphological association and functional covariance
      network organization.
AB  - Local functional homogeneity of the human cortex indicates the boundaries between
      functionally heterogeneous regions and varies remarkably across the cortical
      mantle. It is unclear whether these variations have the neurobiological and
      structural basis. We employed structural and resting-state functional magnetic
      resonance imaging scans from 482 healthy subjects and computed the vertex-wise
      regional homogeneity of low-frequency fluctuations (2dReHo) and five measures of
      cortical morphology. We then used these metrics to examine regional variation,
      morphological association and functional covariance network of 2dReHo. Within the
      ventral visual stream, increases of 2dReHo reflect reduced complexity of
      information processing or functional hierarchies. Along the divisions of the
      prefrontal cortex and posteromedial cortex, the gradients of 2dReHo revealed the
      hierarchical organization within the two association areas, respectively.
      Individual differences in 2dReHo are associated with those of cortical
      morphology, and their whole-brain inter-regional covariation is organized into a
      functional covariance network, comprising five hierarchically organized modules
      with hubs of both primary sensory and high-order association areas. These highly
      reproducible observations suggest that local functional homogeneity has
      neurobiological relevance that is likely determined by anatomical, developmental
      and neurocognitive factors and should serve as a neuroimaging marker to
      investigate the human brain function. 

PMID- 24903826
TI  - Extrastriate projections in human optic radiation revealed by fMRI-informed
      tractography.
AB  - The human optic radiation (OR) is the main pathway for conveying visual input to
      occipital cortex, but it is unclear whether it projects beyond primary visual
      cortex (V1). In this study, we used functional MRI mapping to delineate early
      visual areas in 30 healthy volunteers and determined the termination area of the
      OR as reconstructed with diffusion tractography. Direct thalamo-cortical
      projections to areas V2 and V3 were found in all hemispheres tested, with a
      distinct anatomical arrangement of superior-inferior fiber placement for dorsal
      and ventral projections, respectively, and a medio-lateral nesting arrangement
      for projections to V1, V2 and V3. Finally, segment-specific microstructure was
      examined, revealing sub-fascicular information. This is to date the first in vivo
      demonstration of direct extrastriate projections of the OR in humans. 

PMID- 24903827
TI  - Dissociable roles for hippocampal and amygdalar volume in human fear
      conditioning.
AB  - Fear conditioning is a basic learning process which involves the association of a
      formerly neutral conditioned stimulus (CS) with a biologically relevant aversive
      unconditioned stimulus (US). Previous studies conducted in brain-lesioned
      patients have shown that while the acquisition of autonomic fear responses
      requires an intact amygdala, a spared hippocampus is necessary for the
      development of the CS-US contingency awareness. Although these data have been
      supported by studies using functional neuroimaging techniques in healthy people,
      attempts to extend these findings to the morphological aspects of amygdala and
      hippocampus are missing. Here we tested the hypothesis that amygdalar and
      hippocampal volumes play dissociable roles in determining autonomic responses and
      contingency awareness during fear conditioning. Fifty-two healthy individuals
      (mean age 21.83) underwent high-resolution magnetic resonance imaging. We used a
      differential delay fear conditioning paradigm while assessing skin conductance
      responses (SCRs), subjective ratings of CS-US contingency, as well as emotional
      valence and perceived arousal. Left amygdalar volume significantly predicted the
      magnitude of differential SCRs during fear acquisition, but had no impact on
      contingency learning. Conversely, bilateral hippocampal volumes were
      significantly related to contingency ratings, but not to SCRs. Moreover, left
      amygdalar volume predicted SCRs to the reinforced CS alone, but not those
      elicited by the US. Our findings bridge the gap between previous lesion and
      functional imaging studies, by showing that amygdalar and hippocampal volumes
      differentially modulate the acquisition of conditioned fear. Further, our results
      reveal that the morphology of these limbic structures moderate learning and
      memory already in healthy persons. 

PMID- 24903828
TI  - Do statins increase and Mediterranean diet decrease the risk of breast cancer?
AB  - BACKGROUND: Physical exercise and healthy dietary habits are recommended to
      prevent breast cancer. DISCUSSION: Increased intake of omega-3 fatty acids
      associated with decreased omega-6 - resulting in higher omega-3 to omega-6 ratio
      compared with Western-type diet - is inversely associated with breast cancer
      risk. The modernized Mediterranean diet with high omega-3 to omega-6 ratio, high
      fiber and polyphenol intake, and consumption of low-glycemic index foods reduces
      overall cancer risk and specifically breast cancer risk. It has been suggested
      that consuming no more than one alcoholic drink per day, preferably wine, is
      preferable. Eliminating environmental contaminants, including endocrine
      disruptors, and favoring organic foods to increase polyphenol intake and the
      omega-3 to omega-6 ratios were also shown to be beneficial. Cholesterol-lowering
      statins may decrease antitumor defenses; are toxic for the mitochondria; decrease
      the omega-3 to omega-6 ratio; increase body mass index, insulin resistance and
      diabetic risk; and have been associated with an increased breast cancer risk.
      SUMMARY: Therefore, as well as making lifestyle changes to decrease breast cancer
      risk, we argue that physicians should carefully consider (and often avoid)
      therapies that may increase breast cancer or diabetes risk in high-risk women and
      women who wish to decrease their breast cancer risk.

PMID- 24903831
TI  - Tetrodotoxin-resistant voltage-gated sodium channel Nav 1.8 constitutively
      interacts with ankyrin G.
AB  - The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel Nav 1.8 is
      predominantly expressed in peripheral afferent neurons, but in case of neuronal
      injury an ectopic and detrimental expression of Nav 1.8 occurs in neurons of the
      CNS. In CNS neurons, Nav 1.2 and Nav 1.6 channels accumulate at the axon initial
      segment, the site of the generation of the action potential, through a direct
      interaction with the scaffolding protein ankyrin G (ankG). This interaction is
      regulated by protein kinase CK2 phosphorylation. In this study, we quantitatively
      analyzed the interaction between Nav 1.8 and ankG. GST pull-down assay and
      surface plasmon resonance technology revealed that Nav 1.8 strongly and
      constitutively interacts with ankG, in comparison to what observed for Nav 1.2.
      An ion channel bearing the ankyrin-binding motif of Nav 1.8 displaced the
      endogenous Nav 1 accumulation at the axon initial segment of hippocampal neurons.
      Finally, Nav 1.8 and ankG co-localized in skin nerves fibers. Altogether, these
      results indicate that Nav 1.8 carries all the information required for its
      localization at ankG micro-domains. The constitutive binding of Nav 1.8 with ankG
      could contribute to the pathological aspects of illnesses where Nav 1.8 is
      ectopically expressed in CNS neurons.

PMID- 24903833
TI  - Nutrition and ageing: from phenomenological observations to molecular mechanisms.

PMID- 24903829
TI  - Neuropeptide Y reduces the expression of PLCB2, PLCD1 and selected PLC genes in
      cultured human endothelial cells.
AB  - Endothelial cells (EC) are the first elements exposed to mediators circulating in
      the bloodstream, and react to stimulation with finely tuned responses mediated by
      different signal transduction pathways, leading the endothelium to adapt.
      Neuropeptide Y (NPY), the most abundant peptide in heart and brain, is mainly
      involved in the neuroendocrine regulation of the stress response. The regulatory
      roles of NPY depend on many factors, including its enzymatic processing, receptor
      subtypes and related signal transduction systems, including the phosphoinositide
      (PI) pathway and related phospholipase C (PI-PLC) family of enzymes. The panel of
      expression of PI-PLC enzymes differs comparing quiescent versus differently
      stimulated human EC. Growing evidences indicate that the regulation of the
      expression of PLC genes, which codify for PI-PLC enzymes, might act as an
      additional mechanism of control of the PI signal transduction pathway. NPY was
      described to potentiate the activation of PI-PLC enzymes in different cell types,
      including EC. In the present experiments, we stimulated human umbilical vein EC
      using different doses of NPY in order to investigate a possible role upon the
      expression PLC genes. NPY reduced the overall transcription of PLC genes,
      excepting for PLCE. The most significant effects were observed for PLCB2 and
      PLCD1, both isoforms recruited by means of G-proteins and G-protein-coupled
      receptors. NPY behavior was comparable with other PI-PLC interacting molecules
      that, beside the stimulation of phospholipase activity, also affect the upcoming
      enzymes' production acting upon gene expression. That might represent a mode to
      regulate the activity of PI-PLC enzymes after activation. 

PMID- 24903832
TI  - Social behaviors increase more when children with ASD are imitated by their
      mother vs. an unfamiliar adult.
AB  - Previous research suggests that being imitated by an adult increases the social
      behaviors of children with an autism spectrum disorder (ASD). In the current
      study, we examined whether familiarity with the imitating social partner
      modulates this effect. Ten children with ASD and their mothers participated. The
      children's social behaviors were observed prior to and following a 3-min period
      in which an adult social partner imitated everything they did. In one condition
      the partner was the child's mother, and in the other condition the partner was an
      unfamiliar experimenter. The results revealed significant increases in distal
      social behaviors (gazes toward the adult, vocalizing) following imitation by both
      partners. There was a significantly greater increase in proximal social behaviors
      (including approach, being physically close, and touching) and a greater decrease
      in playing alone when the imitator was the child's mother as opposed to the
      experimenter. The findings suggest that the experience of being imitated creates
      an atmosphere of mutuality and rapport between children with ASD and their social
      partners, which increases their sociability even in interactions with already
      familiar adults.

PMID- 24903830
TI  - Carnosic acid promotes myocardial antioxidant response and prevents isoproterenol
      induced myocardial oxidative stress and apoptosis in mice.
AB  - Carnosic acid is a well-known antioxidant. Recently, it has been identified as
      modulator of nuclear factor erythroid 2-related factor 2 (Nrf2). The effect of
      carnosic acid in the context of cardiovascular disorders has not been studied. In
      the present study, we investigated the beneficial effect and the underlying
      cardioprotective mechanism of carnosic acid by using mouse model of isoproterenol
      (ISO)-induced myocardial stress. Elevated serum levels of Troponin I, CK-MB, LDH,
      SGOT and SGPT, and myofibrillar degeneration with necrotic damage, and the
      presence of epicardial inflammatory infiltrate (H & E staining) confirmed the ISO
      induced myocardial stress. Myocardial content of vitamin C, reduced glutathione,
      glutathione peroxidase, glutathione reductase, glutathione S-transferase,
      NAD(P)H: quinine oxidoreductase 1, superoxide dismutase, catalase, nuclear
      translocation of Nrf2 and protein expression heme oxygenase-1 were evaluated.
      Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and
      myocardial expression of cleaved caspase-3, caspase-9, p53, Bax, and Bcl-2 were
      investigated to assess the apoptotic cell death. Pretreatment with carnosic acid
      attenuated ISO-induced elevated serum levels of Troponin I, CK-MB, LDH, SGOT and
      SGPT, and histopathological alterations in heart. Moreover, carnosic acid
      enhanced the nuclear translocation of Nrf2 and up-regulated the phase
      II/antioxidant enzyme activities. Furthermore, TUNEL assay and apoptosis-related
      protein analysis indicated that carnosic acid prevented ISO-induced cardiomyocyte
      apoptosis. Isoproterenol-induced myocardial lipid peroxidation and protein
      oxidation were also significantly decreased by carnosic acid pretreatment. The
      overall results clearly indicate that therapeutic application of carnosic acid
      might be beneficial in treating cardiovascular disorders.

PMID- 24903834
TI  - Fatty acid synthase methylation levels in adipose tissue: effects of an
      obesogenic diet and phenol compounds.
AB  - DNA methylation is an epigenetic mechanism that can inhibit gene transcription.
      The aim of this study was to assess changes induced by an obesogenic diet in the
      methylation profile of genes involved in adipose tissue triacylglycerol
      metabolism, and to determine whether this methylation pattern can be altered by
      resveratrol and pterostilbene. Rats were divided into four groups. The control
      group was fed a commercial standard diet, and the other three groups were fed a
      commercial high-fat, high-sucrose diet (6 weeks): the high-fat, high-sucrose
      group, the resveratrol-treated group (RSV; 30 mg/kg/day), and the pterostilbene
      treated group (PT; 30 mg/kg/day). Gene expression was measured by RT-PCR and gene
      methylation by pyrosequencing. The obesogenic diet induced a significant increase
      in adipose tissue weight. Resveratrol and pterostilbene partially prevented this
      effect. Methylation pattern of ppnla2 and pparg genes was similar among the
      experimental groups. In fasn, significant hypomethylation in -90-bp position and
      significant hypermethylation in -62-bp position were induced by obesogenic
      feeding. Only pterostilbene reversed the changes induced by the obesogenic diet
      in fasn methylation pattern. By contrast, the addition of resveratrol to the diet
      did not induce changes. Both phenolic compounds averted fasn up-regulation. These
      results demonstrate that the up-regulation of fasn gene induced by an obesogenic
      feeding, based on a high-fat, high-sucrose diet, is related to hypomethylation of
      this gene in position -90 bp. Under our experimental conditions, both molecules
      prevent fasn up-regulation, but this change in gene expression seems to be
      mediated by changes in methylation status only in the case of pterostilbene. 

PMID- 24903835
TI  - Unconventional myosin ID is expressed in myelinating oligodendrocytes.
AB  - Myelin is a dynamic multilamellar structure that ensheathes axons and is crucial
      for normal neuronal function. In the central nervous system (CNS), myelin is
      produced by oligodendrocytes that wrap many layers of plasma membrane around
      axons. The dynamic membrane trafficking system, which relies on motor proteins,
      is required for myelin formation and maintenance. Previously, we found that
      myosin ID (Myo1d), a class I myosin, is enriched in the rat CNS myelin fraction.
      Myo1d is an unconventional myosin and has been shown to be involved in membrane
      trafficking in the recycling pathway in an epithelial cell line. Western blotting
      revealed that Myo1d expression begins early in myelinogenesis and continues to
      increase into adulthood. The localization of Myo1d in CNS myelin has not been
      reported, and the function of Myo1d in vivo remains unknown. To demonstrate the
      expression of Myo1d in CNS myelin and to begin to explore the function of Myo1d
      in myelination, we produced a new antibody against Myo1d that has a high titer
      and specificity for rat Myo1d. By using this antibody, we demonstrated that Myo1d
      is expressed in rat CNS myelin and is especially abundant in abaxonal and
      adaxonal regions (the outer and inner cytoplasm-containing loops, respectively),
      but that expression is low in peripheral nervous system myelin. In culture, Myo1d
      was expressed in mature rat oligodendrocytes. Furthermore, an increase in
      expression of Myo1d during maturation of CNS white matter (cerebellum and corpus
      callosum) was demonstrated by histological analysis. These results suggest that
      Myo1d may be involved in the formation and/or maintenance of CNS myelin.

PMID- 24903836
TI  - [Diagnosis and surgical treatment of postprostatectomy stress incontinence:
      recommendation of the working group Urologische Funktionsdiagnostik und Urologie
      der Frau].
AB  - Today, for the surgical treatment of postprostatectomy incontinence, several
      treatment options are available, e.g., adjustable and functional sling systems,
      artificial sphincter, bulking agents, and balloons. However, no recommendations
      in terms of specific diagnostic tools and differentiated treatment options for
      everyday life are available. Our aim is to provide some clinically relevant
      recommendations for the necessary diagnostic workup and different treatment
      options of postprostatetectomy incontinence to support clinical decisions in
      everyday life. Treatment selection should be based on contraindications. However,
      there is a broad overlap of the various surgical options. 

PMID- 24903837
TI  - [Treatment of nonmetastatic prostate cancer: a systematic review of interactive,
      personalized patient decision aids].
AB  - BACKGROUND: Patients with nonmetastatic prostate cancer face a complex treatment
      decision. To support them with personalized information, a variety of interactive
      computerized decision aids have been developed in Anglo-Saxon countries. Our goal
      was to identify relevant decision aids and investigate their didactic strengths
      and limitations. MATERIALS AND METHODS: We included decision aids that derived
      individualized content from personal and clinical data provided by the patient.
      By conducting a systematic literature and internet research through November 2013
      supplemented by expert interviews, we identified 10 decision aids of which 6 had
      been investigated scientifically. We compared their individual characteristics as
      well as the design and results of the evaluation studies. RESULTS: The decision
      aids present two to seven therapy choices, whereby radical prostatectomy and
      percutaneous radiotherapy are always included. Number and type of parameters
      provided by the patient also vary considerably. Two decision aids derive a
      therapeutic recommendation from the patient's input. Evaluation studies showed
      higher disease-related knowledge and greater confidence in the treatment decision
      after using one of six decision aids. Satisfaction with the decision aid was
      predominantly high. CONCLUSIONS: Currently personalized patient decision aids for
      treatment of nonmetastatic prostate cancer are only available in English. These
      tools can facilitate the shared decision making process for patients and
      physicians. Therefore, comparable decision aids should be developed in German.

PMID- 24903838
TI  - [Cross-sectional analysis of routine treatment for prostate cancer patients:
      CAPRIS - a healthcare research project of the IQUO].
AB  - BACKGROUND: Different practices for the treatment of prostate cancer patients
      exist in Germany. OBJECTIVES: The aim of this analysis was to investigate current
      practice for the treatment of patients with prostate cancer in urological IQUO
      partner practices (Interest Group for Quality Assurance in the Work of Office
      based Uro-oncologists in Germany) dependent on tumor stage and risk factors. The
      analysis focused on T1/T2 and T3/T4 patients. In addition, applied therapies were
      analyzed based on risk group classification (CAPRIS, cancer of the prostate
      identification screening). MATERIALS AND METHODS: This retrospective cross
      sectional analysis includes 1000 patients with prostate cancer with at least 12
      months of documentation from the OnkoDataMed (ODM) database between February 2008
      and May 2012. The 122 IQUO medical practices included were randomly selected;
      maximally 50 patients per practice were included in the analysis. The database
      was analyzed in terms of localized T1/T2 tumors and advanced T3/T4 tumors. Risk
      groups were formed according to parameters of the initial diagnosis including PSA
      value, tumor stage, and Gleason score. Descriptive statistics were performed to
      analyze all parameters. RESULTS AND CONCLUSIONS: As expected, PSA is the critical
      parameter for follow-up and therapy monitoring. Newer therapeutic options have
      only been initiated to a limited extent. Differentiated risk assessment has not
      been sufficiently used; however, it does provide a good opportunity for more
      individualized therapy in the future.

PMID- 24903840
TI  - Is there a trade-off between parent care and self-care?
AB  - Caregiving for family members is often described as a 36-hour day. Previous
      literature has suggested that family caregivers have little time to attend to
      their own health needs, such as participating in leisure-time physical activity.
      Using data from the Health and Retirement Study, we analyze whether time
      allocation decisions reflect a conflict between time devoted to informal care and
      time devoted to self-health promotion through physical activity. The empirical
      model is a system of four correlated equations, wherein the dependent variables
      are hours spent caregiving, frequency of moderate and vigorous physical activity,
      and hours spent in paid work. Results from joint estimation of the four equations
      indicate limited evidence of a competition between time spent in caregiving and
      frequency of physical activity. Parental factors that increase allocation of care
      time to parents do not comprehensively induce reductions in the frequency of any
      type of physical activity, or in hours of work, among either men or women. 

PMID- 24903841
TI  - The effect of prenatal natural disaster exposure on school outcomes.
AB  - This study looks at the impact of exposure to natural disasters during pregnancy
      on the educational outcomes of North Carolina children at the third grade level.
      A broad literature relates negative birth outcomes to poor educational
      performance, and a number of recent studies have examined the effect of prenatal
      exposure to natural disasters on birth outcomes. This study takes the next step
      by considering how prenatal exposure affects later outcomes. Combining North
      Carolina administrative data on births and school performance with disaster
      declarations from the U.S. Federal Emergency Management Agency (FEMA) allows for
      the identification of children who were exposed to disasters during prenatal
      development. These children are compared with other children born in the same
      county who were not exposed to disasters while in utero. Regression results
      suggest that children exposed to hurricanes prenatally have lower scores on third
      grade standardized tests in math and reading. Those exposed to flooding or
      tornadoes also have somewhat lower math scores. Additionally, results suggest
      that these negative effects are more concentrated among children in disadvantaged
      subgroups, especially children born to black mothers. However, no evidence exists
      that these effects are mediated by common measures of birth outcomes, including
      birth weight and gestational age. 

PMID- 24903842
TI  - Prognostic value of cardiac computed tomography angiography in patients with
      suspected coronary artery disease: a meta-analysis.
AB  - OBJECTIVES: The diagnostic accuracy of cardiac computed tomography angiography
      (CCTA) is well reported. The prognostic value of CCTA has been described in
      several studies, but many of these were underpowered and an update of the meta
      analysis is necessary to increase the power to predict rare events. The purpose
      of this study was to perform a meta-analysis of the ability of CCTA to predict
      future cardiovascular events. METHODS: We searched multiple databases for
      longitudinal studies of CCTA with a follow-up of at least 12 months of
      symptomatic patients with suspected coronary artery disease (CAD) reporting major
      adverse cardiovascular events (MACE), death, myocardial infarction and
      revascularization. Summary test parameters and receiver-operating characteristic
      curves were calculated. RESULTS: Eighteen studies evaluated 29,243 patients with
      a median follow-up of 25 months. For MACE in patients with negative findings on
      CCTA, there was a pooled negative likelihood ratio (LR) of 0.01 [95% confidence
      interval (CI) 0.00-0.08], a positive LR of 1.72 (95% CI 1.54-1.91), a sensitivity
      of 1.00 (95% CI 0.97-1.00), a specificity of 0.42 (95% CI 0.36-0.48) and a
      diagnostic odds ratio of 159.07 (95% CI 22.20-1,139.80). The weighted average
      annualized MACE rate for positive versus negative CCTA findings was 3.49 versus
      0.21%. Stratifying by no CAD, nonobstructive CAD or obstructive CAD, there were
      incrementally increasing adverse events. CONCLUSIONS: Adverse cardiovascular
      events among patients with normal findings on CCTA are rare. There are
      incrementally increasing future MACE with increasing CAD by CCTA.

PMID- 24903843
TI  - The role of hemidesmosomes and focal contacts in the skin visualized by dual
      color live cell imaging.
AB  - Live cell imaging is a powerful tool to elucidate dynamics of protein(s). Our
      group has concentrated on dynamics of two major cell-matrix adhesion devices,
      hemidesmosome and focal contact in the keratinocytes. Firstly, we observed the
      fate of hemidesmosome protein or focal contact protein by single-color live cell
      imaging in the physiological setting of keratinocytes. Both hemidesmosome
      proteins and focal contact proteins were highly dynamic. Next, in order to
      observe the interaction between hemidesmosome protein and focal contact protein,
      we observed the fate of these proteins at the same time by dual-color live cell
      imaging in physiological setting and in wound setting of keratinocytes. These
      hemidesmosome proteins and focal contact proteins showed individual dynamics with
      minimal overlap expressions in physiological settings. In sharp contrast, both
      proteins showed highly regulated interaction in wound setting of keratinocytes.
      Finally, we observed the fate of BP180 protein, which is a major target of
      autoimmune bullous disease, bullous pemphigoid, and component of hemidesmosome,
      under the existence of anti-BP180 autoantibody. In results, under such a
      circumstance, BP180 molecules were internalized and thus keratinocyte showed
      weakened adhesion to the cell matrix. Our work has elucidated dynamic aspects of
      cell-matrix adhesion devices under both physiological and pathological
      conditions. 

PMID- 24903844
TI  - Molecular surveillance of non-polio enterovirus infections in patients with acute
      gastroenteritis in Western India: 2004-2009.
AB  - Acute gastroenteritis is a major cause of childhood morbidity and mortality
      worldwide. Rotavirus (RV) and Norovirus (NoV) are the leading cause of the
      disease. Despite the use of improved diagnostic methods a significant proportion
      of gastroenteritis cases remained undiagnosed. Though nonpolio enteroviruses
      (NPEVs) have been reported frequently in children with acute gastroenteritis,
      their etiologic role has not been established. To investigate the epidemiology of
      NPEVs in gastroenteritis cases which remained negative for leading causative
      agents, 955 RV and NoV negative stool specimens from children hospitalized for
      acute gastroenteritis were included in the study. A case control study was
      conducted which includes stool specimens from 450 children with gastroenteritis
      and 162 asymptomatic control subjects to determine the association of NPEVs with
      the disease. NPEV detection and typing was carried out by RT-PCR and sequencing.
      Presence of RV, NoV, Adenovirus, and Astrovirus was confirmed by ELISA or PCR/RT
      PCR. Overall 14% NPEV prevalence was noted. The percentage of children with NPEV
      infection differed significantly between gastroenteritis and non-gastroenteritis
      patients (13.7% vs. 4.9%). NPEV was more prevalent among patients with
      gastroenteritis of undetectable etiology as compared to those detected positive
      for other viruses (17.9% vs. 7%) (P < 0.01). Genotyping of NPEV identified
      predominance of EV-B species (56.5%) followed by EV-C (16.7%), EV-A (13.8%)
      species and mixed NPEV infections (13%). These data support the association of
      NPEVs with acute gastroenteritis and highlights the clinical and epidemiological
      features of NPEV infections in patients with acute gastroenteritis from western
      India.

PMID- 24903845
TI  - Steroid conversion with CYP106A2 - production of pharmaceutically interesting
      DHEA metabolites.
AB  - BACKGROUND: Steroids are lipophilic compounds with a gonane skeleton and play an
      important role in higher organisms. Due to different functionalizations - mainly
      hydroxylations - at the steroid molecule, they vary highly in their mode of
      action. The pharmaceutical industry is, therefore, interested in hydroxysteroids
      as therapeutic agents. The insertion of hydroxyl groups into a steroid core,
      however, is hardly accomplishable by classical chemical means; that is because
      microbial steroid hydroxylations are investigated and applied since decades.
      CYP106A2 is a cytochrome P450 monooxygenase from Bacillus megaterium ATCC 13368,
      which was first described in the late 1970s and which is capable to hydroxylate a
      variety of 3-oxo-delta4 steroids at position 15beta. CYP106A2 is a soluble
      protein, easy to express and to purify in high amounts, which makes this enzyme
      an interesting target for biotechnological purposes. RESULTS: In this work a
      focused steroid library was screened in vitro for new CYP106A2 substrates using a
      reconstituted enzyme assay. Five new substrates were identified, including
      dehydroepiandrosterone and pregnenolone. NMR-spectroscopy revealed that both
      steroids are mainly hydroxylated at position 7beta. In order to establish a
      biotechnological system for the preparative scale production of 7beta
      hydroxylated dehydroepiandrosterone, whole-cell conversions with growing and
      resting cells of B. megaterium ATCC1336 the native host of CYP1062 and also with
      resting cells of a recombinant B. megaterium MS941 strain overexpressing CYP106A2
      have been conducted and conversion rates of 400 muM/h (115 mg/l/h) were obtained.
      Using the B. megaterium MS941 overexpression strain, the selectivity of the
      reaction was improved from 0.7 to 0.9 for 7beta-OH-DHEA. CONCLUSIONS: In this
      work we describe CYP106A2 for the first time as a regio-selective hydroxylase for
      3-hydroxy-delta5 steroids. DHEA was shown to be converted to 7beta-OH-DHEA which
      is a highly interesting human metabolite, supposed to act as neuroprotective,
      anti-inflammatory and immune-modulatory agent. Optimization of the whole-cell
      system using different B. megaterium strains lead to a conversion of DHEA with B.
      megaterium showing high selectivity and conversion rates and displaying a
      volumetric yield of 103 mg/l/h 7beta-OH-DHEA.

PMID- 24903846
TI  - Child-Pugh A hepatitis B-related cirrhotic patients with a single hepatocellular
      carcinoma up to 5 cm: liver transplantation vs. resection.
AB  - OBJECTIVE: This study aims to analyze the outcomes of patients with Child-Pugh A
      class cirrhosis and a single hepatocellular carcinoma (HCC) up to 5 cm in
      diameter who underwent liver transplantation vs. resection. METHODS: During 2007
      to 2012, 282 Child-Pugh A cirrhotic patients with a single HCC up to 5 cm in
      diameter either underwent liver resection (N = 243) or received liver
      transplantation (N = 39) at our center. Patient and tumor characteristics and
      outcomes were analyzed. RESULTS: Patients who underwent liver transplantation had
      a better recurrence-free survival (RFS) vs. those who underwent liver resection.
      However, the 5-year survival rates after these two treatments were comparable.
      Similar results were observed when we analyzed patients with a HCC less than 3
      cm, and for patients with portal hypertension. In the multivariate analysis,
      tumor differentiation, difference of primary treatment, and presence of
      microvascular invasion were associated with postoperative recurrence. However,
      only differentiation negatively impacted overall survival after operation.
      CONCLUSION: Although more recurrences were observed in Child A cirrhotic patients
      with a single HCC up to 5 cm after liver resection, liver resection offers a
      similar 5-year survival to liver transplantation, even for patients with portal
      hypertension.

PMID- 24903847
TI  - Pancreaticogastrostomy versus pancreaticojejunostomy after
      pancreaticoduodenectomy: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: The aim of this systematic review was to compare postoperative
      outcomes between pancreaticogastrostomy and pancreaticojejunostomy after
      pancreaticoduodenectomy. METHODS: Six databases were systematically reviewed to
      identify randomized controlled trials comparing pancreaticogastrostomy and
      pancreaticojejunostomy. Studies reporting postoperative complications,
      reoperations, and mortality were included (PROSPERO registration number
      CRD42013005383). RESULTS: The search provided a total of 1,646 references. Seven
      studies were selected including 1,121 patients, 562 in the pancreaticogastrostomy
      group and 559 in the pancreaticojejunostomy group. Overall incidence of
      pancreatic fistula and the incidence of more severe fistulas (grade B/C) were
      lower in the pancreaticogastrostomy group (relative risk 0.67; 95% confidence
      interval (CI) 0.52 to 0.86; p = 0.002 and relative risk 0.61; 95 % CI 0.40 to
      0.93; p = 0.02). Abdominal collections were more frequent in the
      pancreaticojejunostomy group. However, pancreaticogastrostomy was associated with
      an increased risk of postoperative intraluminal hemorrhage, and there were no
      differences in overall morbidity, reoperations, or mortality. CONCLUSIONS: In
      this systematic review and meta-analysis, a reduction in the incidence of
      postoperative pancreatic fistula in the pancreaticogastrostomy group was
      observed. Although this evidence comes from randomized trials,
      pancreaticogastrostomy cannot be considered superior to pancreaticojejunostomy
      due to the presence of clinical heterogeneity among studies and the absence of
      differences in overall morbidity, reoperations, and mortality.

PMID- 24903848
TI  - Expressive writing promotes self-reported physical, social and psychological
      health among Chinese undergraduates.
AB  - The present study examines the efficacy of expressive writing among Chinese
      undergraduates. The sample comprised of 74 undergraduates enrolled in a 9-week
      intervention (35 in experimental class vs. 39 in control class). The writing
      exercises were well-embedded in an elective course for the two classes. The 46
      item simplified Chinese Self-Rated Health Measurement Scale, which assesses
      psychological, physical and social health, was adopted to measure the outcome of
      this study. Baseline (second week) and post-test (ninth week) scores were
      obtained during the classes. After the intervention on the eighth week, the self
      reported psychological, social and physical health of the experimental class
      improved. Psychological health obtained the maximum degree of improvement,
      followed by social and physical health. Furthermore, female participants gained
      more psychological improvement than males. These results demonstrated that the
      expressive writing approach could improve the physical, social and psychological
      health of Chinese undergraduates, and the method can be applied in university
      psychological consulting settings in Mainland China. 

PMID- 24903849
TI  - Wild Trypanosoma cruzi I genetic diversity in Brazil suggests admixture and
      disturbance in parasite populations from the Atlantic Forest region.
AB  - BACKGROUND: Trypanosoma cruzi (Kinetoplastida, Trypanosomatidae) infection is an
      ancient and widespread zoonosis distributed throughout the Americas.
      Ecologically, Brazil comprises several distinct biomes: Amazonia, Cerrado,
      Caatinga, Pantanal and the Atlantic Forest. Sylvatic T. cruzi transmission is
      known to occur throughout these biomes, with multiple hosts and vectors involved.
      Parasite species-level genetic diversity can be a useful marker for ecosystem
      health. Our aims were to: investigate sylvatic T. cruzi genetic diversity across
      different biomes, detect instances of genetic exchange, and explore the possible
      impact of ecological disturbance on parasite diversity at an intra-species level.
      METHODS: We characterised 107 isolates of T. cruzi I (TcI; discrete typing unit,
      DTU I) from different major Brazilian biomes with twenty-seven nuclear
      microsatellite loci. A representative subset of biologically cloned isolates was
      further characterised using ten mitochondrial gene loci. We compared these data
      generated from Brazilian TcI isolates from around America. RESULTS: Genetic
      diversity was remarkably high, including one divergent cluster that branched
      outside the known genetic diversity of TcI in the Americas. We detected evidence
      for mitochondrial introgression and genetic exchange between the eastern Amazon
      and Caatinga. Finally, we found strong signatures of admixture among isolates
      from the Atlantic Forest region by comparison to parasites from other study
      sites. CONCLUSIONS: Atlantic Forest sylvatic TcI populations are highly
      fragmented and admixed by comparison to others around Brazil. We speculate on:
      the possible causes of Atlantic Forest admixture; the role of T. cruzi as a
      sentinel for ecosystem health, and the impact disrupted sylvatic transmission
      cycles might have on accurate source attribution in oral outbreaks.

PMID- 24903852
TI  - Association of dysmenorrhea with interstitial cystitis/bladder pain syndrome: a
      case-control study.
AB  - OBJECTIVE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic
      disabling condition of the urological system. Many gynecological conditions are
      reported to be associated with IC/BPS. This study presents epidemiological
      evidence of a possible association between dysmenorrhea and IC/BPS, using
      population-based data. DESIGN: A case-control study. SETTING: Taiwan. SAMPLE: The
      study sample was retrieved from Taiwan's Longitudinal Health Insurance Database
      2000, i.e. 291 women aged 18-45 years with a diagnosis of IC/BPS between January
      2000 and December 2010 (cases) and 873 randomly selected controls matched on age
      and index date of ambulatory care visit. We used logistic regression conditioned
      on age to calculate the odds ratio of cases having a prior diagnosis of
      dysmenorrhea relative to controls. RESULTS: Prior dysmenorrhea was found in 87
      (29.9%) cases and in 163 (18.7%) of the controls. Conditional logistic regression
      showed a crude odds ratio of 1.86 (95% confidence interval 1.37-2.52, p < 0.001)
      for prior dysmenorrhea among cases vs. controls. The adjusted odds ratio was 1.59
      (95% confidence interval 1.13-2.23, p = 0.007) after adjusting for medical co
      morbidities. CONCLUSION: This population-based study found that there is an
      association between IC/BPS and prior dysmenorrhea.

PMID- 24903851
TI  - Diagnosing nephrogenic systemic fibrosis in the post-FDA restriction era.
AB  - The emergence of an association between gadolinium-based contrast agents (GBCA)
      and the rare condition nephrogenic systemic fibrosis (NSF) led to a warning in
      2006 from the Food and Drug Administration (FDA) restricting the use of the GBCAs
      to patients with an estimated glomerular filtration rate of >30 mL/min/1.73m(2) .
      We discuss our experience with a post-FDA restriction presentation of NSF and
      subsequent patient death in which the prolonged lead-time of ~5.5 years led to
      challenges in ensuring a secure diagnosis of NSF and establishing risk exposures.
      Accurate contemporary records of contrast administration and clinical factors
      alongside clinical and pathological expertise ensured that we were able to
      confidently diagnose NSF, despite the length of lead time and confounding
      factors.

PMID- 24903850
TI  - Identifying patients with medically unexplained physical symptoms in electronic
      medical records in primary care: a validation study.
AB  - BACKGROUND: When medically unexplained physical symptoms (MUPS) become
      persistent, it may have major implications for the patient, the general
      practitioner (GP) and for society.Early identification of patients with MUPS in
      electronic medical records (EMRs) might contribute to prevention of persistent
      MUPS by creating awareness among GPs and providing an opportunity to start
      stepped care management. However, procedures for identification of patients with
      MUPS in EMRs are not well established yet. In this validation study we explore
      the test characteristics of an EMR screening method to identify patients with
      MUPS. METHODS: The EMR screening method consists of three steps. First, all
      patients >= 18 years were included when they had five or more contacts in the
      last 12 months. Second, patients with known chronic conditions were excluded.
      Finally, patients were included with a MUPS syndrome or when they had three or
      more complaints suggestive for MUPS. We compared the results of the EMR screening
      method with scores on the Patient Health Questionnaire-15 (PHQ-15), which we used
      as reference test. We calculated test characteristics for various cut-off points.
      RESULTS: From the 1223 patients in our dataset who completed the PHQ-15, 609
      (49/8%) scored >= 5 on the PHQ-15. The EMR screening method detected 131/1223
      (10.7%) as patients with MUPS. Of those, 102 (77.9%) scored >= 5 on the PHQ-15
      and 53 (40.5%) scored >= 10. When compared with the PHQ-15 cut-off point >= 10,
      sensitivity and specificity were 0.30 and 0.93 and positive and negative
      predictive values were 0.40 and 0.89, respectively. CONCLUSIONS: The EMR
      screening method to identify patients with MUPS has a high specificity. However,
      many potential MUPS patients will be missed. Before using this method as a
      screening instrument for selecting patients who might benefit from structured
      care, its sensitivity needs to be improved while maintaining its specificity.

PMID- 24903853
TI  - Barriers of healthcare providers against end-of-life discussions with pediatric
      cancer patients.
AB  - OBJECTIVE: End-of-life discussions with patients can be one of the most difficult
      and stressful tasks for the oncologist. However, little is known about the
      discussions that healthcare providers have with patients in such situations and
      the difficulties they face. The primary end points of this study were to describe
      the contents of end-of-life discussion in the pediatric setting and the barriers
      to end-of-life discussion for pediatric patients, as perceived by pediatric
      healthcare providers. METHODS: Participants were 10 healthcare providers. Semi
      structured interviews were conducted, and the KJ method was performed to analyze
      the data. RESULTS: We found 23 barriers against end-of-life discussion with
      pediatric cancer patients. These barriers were classified as follows: healthcare
      provider factors, patient factors, parent factors and institutional or cultural
      factors. In addition to barriers found in previous studies, some unique barriers
      were uncovered such as, 'Lack of confidence to face the patient after the
      discussion', 'Uncertain responsibility for treatment decision-making' and 'No
      compelling reason to discuss'. Healthcare providers actively discussed the
      purpose of treatment and the patients' wishes and concerns; however, they were
      reluctant to deal with the patients' own impending death and their estimated
      prognosis. CONCLUSIONS: End-of-life discussion with pediatric patients differs
      from that with adult patients. Further studies are required to analyze pediatric
      cases associated with end-of-life discussion and carefully discuss its adequacy,
      pros and cons.

PMID- 24903854
TI  - Radiation-induced breast angiosarcoma with a confirmative feature of c-MYC
      amplification.

PMID- 24903856
TI  - Defect creation by linker fragmentation in metal-organic frameworks and its
      effects on gas uptake properties.
AB  - We successfully demonstrate an approach based on linker fragmentation to create
      defects and tune the pore volumes and surface areas of two metal-organic
      frameworks, NU-125 and HKUST-1, both of which feature copper paddlewheel nodes.
      Depending on the linker fragment composition, the defect can be either a vacant
      site or a functional group that the original linker does not have. In the first
      case, we show that both surface area and pore volume increase, while in the
      second case they decrease. The effect of defects on the high-pressure gas uptake
      is also studied over a large temperature and pressure range for different gases.
      We found that despite an increase in pore volume and surface area in structures
      with vacant sites, the absolute adsorption for methane decreases for HKUST-1 and
      slightly increases for NU-125. However, the working capacity (deliverable amount
      between 65 and 5 bar) in both cases remains similar to parent frameworks due to
      lower uptakes at low pressures. In the case of NU-125, the effect of defects
      became more pronounced at lower temperatures, reflecting the greater surface
      areas and pore volumes of the altered forms. 

PMID- 24903855
TI  - Reproductive and developmental effects of phthalate diesters in males.
AB  - Phthalate diesters are a diverse group of chemicals used to make plastics
      flexible and are found in personal care products, medical equipment, and
      medication capsules. Ubiquitous in the environment, human exposure to phthalates
      is unavoidable; however, the clinical relevance of low concentrations in human
      tissues remains uncertain. The epidemiological literature was inadequate for
      prior reviews to conclusively evaluate the effects of phthalates on male
      reproductive tract development and function, but recent studies have expanded the
      literature. Therefore, we conducted a systematic review of the literature focused
      on the effects of phthalate exposure on the developing male reproductive tract,
      puberty, semen quality, fertility, and reproductive hormones. We conclude that
      although the epidemiological evidence for an association between phthalate
      exposure and most adverse outcomes in the reproductive system, at concentrations
      to which general human populations are exposed, is minimal to weak, the evidence
      for effects on semen quality is moderate. Results of animal studies reveal that,
      although DEHP was the most potent, different phthalates have similar effects and
      can adversely affect development of the male reproductive tract with semen
      quality being the most sensitive outcome. We also note that developmental
      exposure in humans was within an order of magnitude of the adverse effects
      documented in several animal studies. While the mechanisms underlying phthalate
      toxicity remain unclear, the animal literature suggests that mice are less
      sensitive than rats and potentially more relevant to estimating effects in
      humans. Potential for chemical interactions and effects across generations
      highlights the need for continued study.

PMID- 24903858
TI  - Freudian modalities of disbelief.
AB  - This article can be characterized as a 'rediscovery' of a notion of
      psychoanalysis that had disappeared or had been confused by later operations. The
      authors explore a Freudian notion that has been unjustly misunderstood,
      especially because of the multiple ways in which 'Unglaube' - disbelief - has
      been translated. We shall establish the archaeology of this term in Freud by
      extracting its three significant modes. Firstly, paranoiac disbelief designates
      an unconscious process of the rejection of belief in the subject's first
      encounter with a sexual reality that is always traumatic. Secondly, the
      obsessional neurotic's disbelief, which we shall call 'incredulity', is a
      secondary, less radical refusal of belief, one that is different from its
      paranoiac counterpart. Finally, we shall envision a third - dialectical - type of
      disbelief, which Freud called 'act of disbelief' and which will enable us to
      approach the fundamental epistemic and ethical stakes for psychoanalysis. 

PMID- 24903857
TI  - Adenosine triphosphate drives head and neck cancer pain through P2X2/3
      heterotrimers.
AB  - INTRODUCTION: Cancer pain creates a poor quality of life and decreases survival.
      The basic neurobiology of cancer pain is poorly understood. Adenosine
      triphosphate (ATP) and the ATP ionotropic receptor subunits, P2X2 and P2X3,
      mediate cancer pain in animal models; however, it is unknown whether this
      mechanism operates in human, and if so, what the relative contribution of P2X2-
      and P2X3-containing trimeric channels to cancer pain is. Here, we studied head
      and neck squamous cell carcinoma (HNSCC), which causes the highest level of
      function-induced pain relative to other types of cancer. RESULTS: We show that
      the human HNSCC tissues contain significantly increased levels of ATP compared to
      the matched normal tissues. The high levels of ATP are secreted by the cancer and
      positively correlate with self-reported function-induced pain in patients. The
      human HNSCC microenvironment is densely innervated by nerve fibers expressing
      both P2X2 and P2X3 subunits. In animal models of HNSCC we showed that ATP in the
      cancer microenvironment likely heightens pain perception through the P2X2/3
      trimeric receptors. Nerve growth factor (NGF), another cancer-derived pain
      mediator found in both human and mouse HNSCC, induces P2X2 and P2X3
      hypersensitivity and increases subunit expression in murine trigeminal ganglion
      (TG) neurons. CONCLUSIONS: These data identify a key peripheral mechanism in
      cancer pain and highlight the clinical potential of specifically targeting
      nociceptors expressing both P2X2 and P2X3 subunits (e.g., P2X2/3 heterotrimers)
      to alleviate cancer pain.

PMID- 24903859
TI  - Does the falls efficacy scale international version measure fear of falling: a
      reassessment of internal validity using a factor analytic approach.
AB  - BACKGROUND: the Falls Efficacy Scale-International (FES-I) is a widely used
      measure of fear of falling that assesses concerns with respect to falls over a
      range of physical and social activities. In the original validation study, the
      methods used (self-selection by participants) were likely to over-represent those
      with a higher educational level and socio-economic grouping. In addition, the
      factor analysis method used was potentially less applicable to older individuals
      and may have been less likely to measure the construct of fear of falling.
      OBJECTIVE: to validate the internal validity of the FES-I and assess its
      suitability as a measure of fear of falling. DESIGN: cross-sectional survey.
      SETTING: community sample. METHODS: a random sample of 200 participants aged 60
      years completed the FES-I by structured interview. We verify internal validity
      with a factor analytic approach not previously employed in this study design
      context, principal factor analysis on the matrix of polychoric correlations.
      RESULTS: we find no redundancy in the questions on the FES-I. All are found to
      strongly represent concerns about falling during social and physical activities.
      CONCLUSION: the FES-I is an appropriate tool to assess fear or concerns with
      respect to falls in the general elderly population, and more appropriately
      represents concern of falling than has previously been found. Future health
      services research with the FES-I should have its design informed by the results
      presented in this study, as the structure of the 'concern with falling' factor
      differs markedly from that found in previous validity testing.

PMID- 24903860
TI  - Shifts in hormonal stress reactivity during adolescence are not associated with
      changes in glucocorticoid receptor levels in the brain and pituitary of male
      rats.
AB  - Preadolescent animals display protracted hormonal stress responses mediated by
      the hypothalamic-pituitary-adrenal (HPA) axis compared to adults. Though the
      mechanisms that underlie this shift in stress reactivity are unknown, reduced
      glucocorticoid-dependent negative feedback on the HPA axis has been posited to
      contribute to this differential responsiveness. As the glucocorticoid receptors
      (GRs) are integral to this feedback response, we hypothesize that prior to
      puberty there will be fewer GRs in the neural-pituitary network that mediate
      negative feedback. To test this hypothesis we measured GR protein levels in the
      brains of preadolescent (28 days old), midadolescent (40 days old) and adult (77
      days old) male rats via immunohistochemistry. Additionally, we assessed stress
      induced plasma adrenocorticotropic hormone and corticosterone in prepubertal (30
      days old) and adult (70 days old) male rats and examined GR protein levels via
      Western blot in the brain and pituitary. We found that despite substantial
      adolescent-related changes in hormonal responsiveness, no significant differences
      were found between these ages in GR protein levels in regions that are important
      in negative feedback, including the medial prefrontal cortex, paraventricular
      nucleus of the hypothalamus, hippocampal formation, and pituitary. These data
      indicate that the extended hormonal stress response exhibited by preadolescent
      animals is independent of significant pubertal changes in GR protein levels.

PMID- 24903861
TI  - Comparisons between the attitudes of medical and dental students toward the
      clinical importance of gross anatomy and physiology.
AB  - Marked changes are occurring within both the medical and dental curricula and new
      ways of teaching the basic sciences have been devised and traditional methods
      (e.g., dissection for gross anatomy and of bench-based animal preparations for
      physiology) are increasingly no longer the norm. Although there is much anecdotal
      evidence that students are not in favor of such changes, there is little evidence
      for this based on quantitative analyses of students' attitudes. Using Thurstone
      and Chave attitude analyses, we assessed the attitudes of first year medical and
      dental students at Cardiff University toward gross anatomy and physiology in
      terms of their perceived clinical importance. In addition, we investigated the
      appropriateness ("fitness for purpose") of teaching methodologies used for
      anatomy and physiology. The hypotheses tested recognized the possibility that
      medical and dental students differed in their opinions, but that they had a
      preference to being taught gross anatomy through the use of dissection and had no
      preference for physiology teaching. It was found that both medical and dental
      students displayed positive attitudes toward the clinical relevance of gross
      anatomy and that they preferred to be taught by means of dissection. Although
      both medical and dental students displayed positives attitudes toward the
      clinical relevance of physiology, this was greater for the medical students. Both
      medical and dental students showed a preference for being taught physiology
      through didactic teaching in small groups but the medical students also
      appreciated being taught by means of practicals. Overall, this study highlights
      the expectations that students have for the basic science foundation teaching
      within their professional training and signals a preference for being taught
      experientially/practically. Differences were discerned between medical and dental
      students that might reflect the direct association between systems physiology and
      pathophysiology and the application of this knowledge within the medical field in
      comparison to the dental field, which is heavily skill-based.

PMID- 24903862
TI  - Genome Sequences of Two Temperate Phages, PhiCB2047-A and PhiCB2047-C, Infecting
      Sulfitobacter sp. Strain 2047.
AB  - We announce the complete genome sequences of two temperate Podoviridae,
      Sulfitobacter phages PhiCB2047-A and PhiCB2047-C, which infect Sulfitobacter sp.
      strain 2047, a member of the Roseobacter clade. This is the first report of
      temperate podophage infecting members of the Sulfitobacter genus of the
      Roseobacter clade. 

PMID- 24903863
TI  - Draft Genome Sequence of Xanthomonas arboricola pv. pruni Strain Xap33, Causal
      Agent of Bacterial Spot Disease on Almond.
AB  - We report the annotated genome sequence of Xanthomonas arboricola pv. pruni
      strain Xap33, isolated from almond leaves showing bacterial spot disease symptoms
      in Spain. The availability of this genome sequence will aid our understanding of
      the infection mechanism of this bacterium as well as its relationship to other
      species of the same genus. 

PMID- 24903864
TI  - Whole-Genome Sequences of Low-Virulence Strain CB3 and Mild Strain CB7 of
      Chlamydia psittaci.
AB  - Avian Chlamydia psittaci is an obligate intracellular zoonotic pathogen
      especially dispersed from birds, and it is known to cause pericarditis,
      pneumonia, lateral nasal adenitis, peritonitis, hepatitis, splenitis, and other
      diseases. Generalized infections result in fever, anorexia, lethargy, and
      diarrhea, depending on the chlamydial genotype and the affected bird species.
      Although many complete genomes of C. psittaci have been sequenced, we report here
      the genomes of two strains isolated from the free-living sparrows (strain CB3)
      and vinous-throated parrotbill (strain CB7) in China, which were first isolated
      from the spleens of healthy birds in a routine investigation. 

PMID- 24903865
TI  - Draft Genome Sequence of Defluviimonas indica Strain 20V17T, Isolated from a Deep
      Sea Hydrothermal Vent Environment in the Southwest Indian Ocean.
AB  - Here, we present the draft genome sequence of Defluviimonas indica 20V17(T),
      which was isolated from a deep-sea hydrothermal vent chimney sample in the
      southwest Indian Ocean. The draft genome sequence contains 4,268,338 bp, with a
      G+C content of 66.33%. 

PMID- 24903866
TI  - Genome Sequences of Two Leuconostoc pseudomesenteroides Strains Isolated from
      Danish Dairy Starter Cultures.
AB  - The lactic acid bacterium Leuconostoc pseudomesenteroides can be found in
      mesophilic cheese starters, where it produces aromatic compounds from, e.g.,
      citrate. Here, we present the draft genome sequences of two L.
      pseudomesenteroides strains isolated from traditional Danish cheese starters. 

PMID- 24903867
TI  - Genome Sequence of Leuconostoc mesenteroides subsp. cremoris Strain T26, Isolated
      from Mesophilic Undefined Cheese Starter.
AB  - Leuconostoc is the main group of heterofermentative bacteria found in mesophilic
      dairy starters. They grow in close symbiosis with the Lactococcus population and
      are able to degrade citrate. Here we present a draft genome sequence of
      Leuconostoc mesenteroides subsp. cremoris strain T26. 

PMID- 24903868
TI  - Complete Genome Sequence of a Newcastle Disease Virus Isolated from Wild Peacock
      (Pavo cristatus) in India.
AB  - We report here the complete genome sequence of a Newcastle disease virus (NDV)
      isolated from a wild peacock. Phylogenetic analysis showed that it belongs to
      genotype II, class II of NDV strains. This study helps to understand the ecology
      of NDV strains circulating in a wild avian host of this geographical region
      during the outbreak of 2012 in northwest India. 

PMID- 24903869
TI  - Complete coding sequence of zika virus from a French polynesia outbreak in 2013.
AB  - Zika virus is an arthropod-borne Flavivirus member of the Spondweni serocomplex,
      transmitted by Aedes mosquitoes. We report here the complete coding sequence of a
      Zika virus strain belonging to the Asian lineage, isolated from an infected
      patient returning from French Polynesia, an epidemic area in 2013/2014. 

PMID- 24903870
TI  - Draft Genome Sequence of Pseudomonas sp. Strain Ant30-3, a Psychrotolerant
      Bacterium with Biodegradative Attribute Isolated from Antarctica.
AB  - Pseudomonas sp. strain Ant30-3, isolated from fuel-contaminated Antarctic soil,
      exhibited distinctive psychrotolerant attributes and the potential for degrading
      aromatic hydrocarbon compounds at cold temperatures. We report here the 6.14-Mb
      draft genome of Ant30-3, which will provide insights into the genomic basis for
      the psychrotolerant and biodegradative properties of this bacterium. 

PMID- 24903872
TI  - Genome Sequence of a Promising Hydrogen-Producing Facultative Anaerobic
      Bacterium, Brevundimonas naejangsanensis Strain B1.
AB  - Brevundimonas naejangsanensis strain B1 is a newly isolated, facultative
      anaerobic bacterium capable of producing hydrogen with high efficiency. Here, we
      present a 2.94-Mb assembly of the genome sequence of strain B1, which may provide
      further insights into the molecular mechanism of hydrogen production from
      bioresource. 

PMID- 24903871
TI  - Draft Genome Sequence of the Mycobacterium tuberculosis Clinical Isolate C2,
      Belonging to the Latin American-Mediterranean Family.
AB  - Tuberculosis remains a major infectious disease in Taiwan. Here we present the
      draft genome sequence of the Mycobacterium tuberculosis C2 strain, belonging to
      the Latin American-Mediterranean lineage. The draft genome sequence comprises
      4,453,307 bp with a G+C content of 65.6%, revealing 4,390 coding genes and 45
      tRNA genes. 

PMID- 24903873
TI  - Complete Genome Sequence of the Highly Transformable Pseudomonas stutzeri Strain
      28a24.
AB  - Here, we report the complete genome sequence for an isolate of Pseudomonas
      stutzeri that is highly competent for natural transformation. This sequence
      enables insights into the genetic basis of natural transformation rate variations
      and provides an additional data point for genomic comparisons across a ubiquitous
      and highly diverse bacterial species. 

PMID- 24903874
TI  - Avian Influenza Virus with Hemagglutinin-Neuraminidase Combination H8N8, Isolated
      in Russia.
AB  - We report the genome sequence of an avian influenza virus (AIV) subtype H8N8,
      isolated in Russia. The genome analysis shows that all genes belong to AIV
      Eurasian lineages. The PB2 gene was similar to a Mongolian low-pathogenic (LP)
      AIV H7N1 and a Chinese high-pathogenic (HP) AIV H5N2. 

PMID- 24903875
TI  - Draft Genome Sequence of Aspergillus oryzae 100-8, an Increased Acid Protease
      Production Strain.
AB  - Aspergillus oryzae is a common fungus for traditional fermentation in Asia, such
      as spirit, soybean paste, and soy sauce fermentation. We report the 36.7-Mbp
      draft genome sequence of A. oryzae 100-8 and compared it to the published genome
      sequence of A. oryzae 3.042. 

PMID- 24903876
TI  - Draft Genome Sequence of Acetobacter aceti Strain 1023, a Vinegar Factory
      Isolate.
AB  - The genome sequence of Acetobacter aceti 1023, an acetic acid bacterium adapted
      to traditional vinegar fermentation, comprises 3.0 Mb (chromosome plus plasmids).
      A. aceti 1023 is closely related to the cocoa fermenter Acetobacter pasteurianus
      386B but possesses many additional insertion sequence elements. 

PMID- 24903877
TI  - Genome Sequences of Seven Mycoplasma hyosynoviae Strains Isolated from the Joint
      Tissue of Infected Swine (Sus scrofa).
AB  - Mycoplasma hyosynoviae is a Gram-negative bacterium that can cause debilitating
      arthritis in swine. Currently, there are no M. hyosynoviae genome sequences in
      the GenBank database, which makes it impossible to understand its pathogenesis,
      nutrition, or colonization characteristics, or to devise an effective strategy
      for its control. Here, we report the genome sequences of seven strains of M.
      hyosynoviae. Within each genome, several virulence factors were identified that
      may prove important in the pathogenesis of M. hyosynoviae-mediated arthritis and
      serve as potential virulence markers that may be critical in vaccine development.

PMID- 24903878
TI  - Complete Genome Sequence of a Virulent Strain, Streptococcus iniae ISET0901,
      Isolated from Diseased Tilapia.
AB  - Streptococcus iniae ISET0901 is a virulent strain isolated in 2007 from diseased
      tilapia. Its full genome is 2,070,856 bp. The availability of this genome will
      allow comparative genomics to identify virulence genes important for the
      pathogenesis of streptococcosis caused by S. iniae, as well as possible
      immunogens for vaccine development. 

PMID- 24903879
TI  - Complete Genome Sequence of a Moderately Virulent Aeromonas hydrophila Strain,
      pc104A, Isolated from Soil of a Catfish Pond in West Alabama.
AB  - Aeromonas hydrophila pc104A is a moderately virulent strain isolated from the
      soil of a catfish pond in west Alabama in 2010. Its full genome is 5,023,829 bp.
      The availability of this genome will allow comparative genomics to identify the
      virulence genes that are important for pathogenesis or immunogens for the purpose
      of vaccine development. 

PMID- 24903880
TI  - Draft Genome Sequence of Geobacillus thermopakistaniensis Strain MAS1.
AB  - Geobacillus thermopakistaniensis strain MAS1 was isolated from a hot spring
      located in the Northern Areas of Pakistan. The draft genome sequence was 3.5 Mb
      and identified a number of genes of potential industrial importance, including
      genes encoding glycoside hydrolases, pullulanase, amylopullulanase, glycosidase,
      and alcohol dehydrogenases. 

PMID- 24903881
TI  - Draft Genome Sequences of Geobacillus sp. Strains CAMR5420 and CAMR12739.
AB  - Thermophilic Geobacillus spp. can efficiently hydrolyze hemicellulose polymers
      and are therefore of interest in biotechnological applications. Here we report
      the genome sequences of two hemicellulolytic strains, Geobacillus sp. CAMR12739
      and CAMR5420. 

PMID- 24903882
TI  - Complete Genome Sequences of Salmonella enterica Serovar Heidelberg Strains
      Associated with a Multistate Food-Borne Illness Investigation.
AB  - Next-generation sequencing is being evaluated for use with food-borne illness
      investigations, especially when the outbreak strains produce patterns that cannot
      be discriminated from non-outbreak strains using conventional procedures. Here we
      report complete genome assemblies of two Salmonella enterica serovar Heidelberg
      strains with a common pulsed-field gel electrophoresis pattern isolated during an
      outbreak investigation. 

PMID- 24903883
TI  - Nanolithography based on metalized DNA templates for graphene patterning.
AB  - DNA self-assembly, such as DNA origami and single-stranded tile (SST) assembly,
      can create complex nanostructures with prescribed two-dimensional (2-D) and three
      dimensional (3-D) shapes. Distinct patterned DNA nanostructures can be used as
      templates or shadow masks for the lithographic patterning of 2-D thin-film
      materials for nanodevices. The protocols in this article describe a general
      procedure of metalized DNA nanolithography based upon DNA metalization and
      subsequent etching to transfer the shape information from DNA templates to
      graphene, such that the shape of complex graphene nanostructures can be
      rationally programmed. Spatial information within the predesigned DNA patterns,
      such as width, orientation, curvature, and angles, can be successfully
      transferred to the graphene nanostructures with sub-10 nm resolution. This method
      could be further generalized to enable patterning of nano-sized modules of
      graphene and other 2-D electronic materials with predesigned shapes for complex
      electronic and quantum circuits.

PMID- 24903884
TI  - Manipulating natural product biosynthetic pathways via DNA assembler.
AB  - DNA assembler is an efficient synthetic biology method for constructing and
      manipulating biochemical pathways. The rapidly increasing number of sequenced
      genomes provides a rich source for discovery of gene clusters involved in
      synthesizing new natural products. However, both discovery and economical
      production are hampered by our limited knowledge in manipulating most organisms
      and the corresponding pathways. By taking advantage of yeast in vivo homologous
      recombination, DNA assembler synthesizes an entire expression vector containing
      the target biosynthetic pathway and the genetic elements needed for DNA
      maintenance and replication. Here we use the spectinabilin clusters originated
      from two hosts as examples to illustrate the guidelines of using DNA assembler
      for cluster characterization and silent cluster activation. Such strategies offer
      unprecedented versatility in cluster manipulation, bypass the traditional
      laborious strategies to elicit pathway expression, and provide a new platform for
      de novo cluster assembly and genome mining for discovering new natural products.

PMID- 24903885
TI  - Synthesis of hydrogen-bond surrogate alpha-helices as inhibitors of protein
      protein interactions.
AB  - The alpha-helix is a prevalent secondary structure in proteins and is critical in
      mediating protein-protein interactions (PPIs). Peptide mimetics that adopt stable
      helices have become powerful tools for the modulation of PPIs in vitro and in
      vivo. Hydrogen-bond surrogate (HBS) alpha-helices utilize a covalent bond in
      place of an N-terminal i to i+4 hydrogen bond and have been used to target and
      disrupt PPIs that become dysregulated in disease states. These compounds have
      improved conformational stability and cellular uptake as compared to their linear
      peptide counterparts. The protocol presented here describes current methodology
      for the synthesis of HBS alpha-helical mimetics. The solid-phase synthesis of HBS
      helices involves solid-phase peptide synthesis with three key steps involving
      incorporation of N-allyl functionality within the backbone of the peptide,
      coupling of a secondary amine, and a ring-closing metathesis step.

PMID- 24903886
TI  - Rapid assays for lectin toxicity and binding changes that reflect altered
      glycosylation in mammalian cells.
AB  - Glycosylation engineering is used to generate glycoproteins, glycolipids, or
      proteoglycans with a more defined complement of glycans on their glycoconjugates.
      For example, a mammalian cell glycosylation mutant lacking a specific
      glycosyltransferase generates glycoproteins, and/or glycolipids, and/or
      proteoglycans with truncated glycans missing the sugar transferred by that
      glycosyltransferase, as well as those sugars that would be added subsequently. In
      some cases, an alternative glycosyltransferase may then use the truncated glycans
      as acceptors, thereby generating a new or different glycan subset in the mutant
      cell. Another type of glycosylation mutant arises from gain-of-function mutations
      that, for example, activate a silent glycosyltransferase gene. In this case,
      glycoconjugates will have glycans with additional sugar(s) that are more
      elaborate than the glycans of wild type cells. Mutations in other genes that
      affect glycosylation, such as nucleotide sugar synthases or transporters, will
      alter the glycan complement in more general ways that usually affect several
      types of glycoconjugates. There are now many strategies for generating a precise
      mutation in a glycosylation gene in a mammalian cell. Large-volume cultures of
      mammalian cells may also generate spontaneous mutants in glycosylation pathways.
      This article will focus on how to rapidly characterize mammalian cells with an
      altered glycosylation activity. The key reagents for the protocols described are
      plant lectins that bind mammalian glycans with varying avidities, depending on
      the specific structure of those glycans. Cells with altered glycosylation
      generally become resistant or hypersensitive to lectin toxicity, and have reduced
      or increased lectin or antibody binding. Here we describe rapid assays to compare
      the cytotoxicity of lectins in a lectin resistance test, and the binding of
      lectins or antibodies by flow cytometry in a glycan-binding assay. Based on these
      tests, glycosylation changes expressed by a cell can be revealed, and
      glycosylation mutants classified into phenotypic groups that may reflect a loss
      of-function or gain-of-function mutation in a specific gene involved in glycan
      synthesis.

PMID- 24903887
TI  - Structural basis for low-affinity binding of non-R2 carboxylate-substituted
      tricyclic quinoline analogs to CK2alpha: comparative molecular dynamics
      simulation studies.
AB  - Protein kinase CK2 is a novel potential target for cancer treatment. The
      tricyclic quinoline compound CX-4945 (R2 = COOH) is the first bioavailable CK2
      inhibitor used in human clinical trials for advanced solid tumors. CX-4945
      analogs with non-R2 carboxylate function were demonstrated to be approximately
      5000-fold less potent than compound 12 (R2 = COOH) in vitro. Molecular docking
      and molecular dynamics simulations were employed to elucidate the structural
      mechanisms through which the R2 non-ionizable and R3 carboxylic acid substituents
      influence binding affinity. Results show that the structure of CK2alpha and the
      orientation of ligands changed to different degrees in non-R2 carboxylate
      function systems. The inappropriate electrostatic interactions between the non-R2
      carboxylate group and the positive region lead to improper protein-ligand
      recognition, which is followed by the reorientation of tricyclic skeletons. For
      CK2alpha, the affected positions are distributed over the glycine-rich loop (G
      loop), C-loop, and the beta4/beta5 loop. The allosteric mechanisms between the
      deviated ligands and the changed regions are proposed. Detailed energy
      calculation and residue-based energy decomposition indicate the energetic
      influences on the contributions of the critical residues. These results are in
      accordance with one another and could provide rational clues to the design of
      more potent CK2 inhibitors.

PMID- 24903889
TI  - Homogeneous and label-free detection of microRNAs using bifunctional strand
      displacement amplification-mediated hyperbranched rolling circle amplification.
AB  - MicroRNAs (miRNAs) are an emerging class of biomarkers and therapeutic targets
      for various diseases including cancers. Here, we develop a homogeneous and label
      free method for sensitive detection of let-7a miRNA based on bifunctional strand
      displacement amplification (SDA)-mediated hyperbranched rolling circle
      amplification (HRCA). The binding of target miRNA with the linear template
      initiates the bifunctional SDA reaction, generating two different kinds of
      triggers which can hybridize with the linear template to initiate new rounds of
      SDA reaction for the production of more and more triggers. In the meantime, the
      released two different kinds of triggers can function as the first and the second
      primers, respectively, to initiate the HRCA reaction whose products can be simply
      monitored by a standard fluorometer with SYBR Green I as the fluorescent
      indicator. The proposed method exhibits high sensitivity with a detection limit
      of as low as 1.8 * 10(-13) M and a large dynamic range of 5 orders of magnitude
      from 0.1 pM to 10 nM, and it can even discriminate the single-base difference
      among the miRNA family members. Moreover, this method can be used to analyze the
      total RNA samples from the human lung tissues and might be further applied for
      sensitive detection of various proteins, small molecules, and metal ions in
      combination with specific aptamers. 

PMID- 24903888
TI  - Triglyceride-raising APOA5 genetic variants are associated with obesity and non
      HDL-C in Chinese children and adolescents.
AB  - BACKGROUND: Although the association between the apolipoprotein A5 (APOA5)
      genetic variants and hypertriglyceridemia has been extensively studied, there
      have been few studies, particularly in children and adolescents, on the
      association between APOA5 genetic variants and obesity or non-high-density
      lipoprotein cholesterol (non-HDL-C) levels. The objective of this study was to
      examine whether APOA5 gene polymorphisms affect body mass index (BMI) or plasma
      non-HDL-C levels in Chinese child population. METHODS: This was a case-control
      study. Single nucleotide polymorphisms (SNPs) were genotyped using Matrix
      Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for an
      association study in 569 obese or overweight and 194 healthy Chinese children and
      adolescents. RESULTS: Genotype distributions for all polymorphisms in both
      cohorts were in accordance with the Hardy-Weinberg distribution. The frequencies
      of the risk alleles in rs662799 and rs651821 SNPs in APOA5 gene were all
      increased in obese or overweight patients compared to the controls. After
      adjusted for age and sex, C carriers in rs662799 had a 1.496-fold [95% confidence
      interval (CI): 1.074-2.084, P = 0.017] higher risk for developing obesity or
      overweight than subjects with TT genotype, while C carriers in rs651821 had a
      1.515-fold higher risk than subjects with TT genotype (95% CI: 1.088-2.100, P =
      0.014). Triglyceride (TG) and non-HDL-C concentrations were significantly
      different among rs662799 variants and both were higher in carriers of minor
      allele than in noncarriers for TG (1.64 +/- 0.96 vs. 1.33 +/- 0.67 mmol/L) (P <
      0.001), and for non-HDL-C (3.23 +/- 0.92 vs. 3.02 +/- 0.80 mmol/L) (P = 0.005),
      respectively. There was also a trend towards increased TG and non-high-density
      lipoprotein cholesterol levels for rs651821 C carriers (P < 0.001 and P = 0.002,
      respectively). Furthermore, to confirm the independence of the associations
      between APOA5 gene and TG or non-HDL-C levels, multiple linear regression
      analysis was performed and the relationships were not eliminated by adjustment
      for age, sex and BMI. CONCLUSIONS: These findings suggest the TG-raising genetic
      variants in the APOA5 gene may influence the susceptibility of the individual to
      obesity, which may also contribute to an increased risk of high non-HDL-C levels
      in Chinese obese children and adolescents.

PMID- 24903890
TI  - Optimal liver allocation for hepatocellular carcinoma: hurry up AND wait, but
      which one when?

PMID- 24903891
TI  - Severe systemic calciphylaxis in a young cat.

PMID- 24903892
TI  - Sexual orientation, social capital and daily tobacco smoking: a population-based
      study.
AB  - BACKGROUND: Studies have suggested poorer health in the homosexual and bisexual
      groups compared to heterosexuals. Tobacco smoking, which is a health-related
      behavior associated with psychosocial stress, may be one explanation behind such
      health differences. Social capital, i.e. the generalized trust in other people
      and social participation/social networks which decreases the costs of social
      interaction, has been suggested to affect health through psychosocial pathways
      and through norms connected with health related behaviours, The aim of this study
      is to investigate the association between sexual orientation and daily tobacco
      smoking, taking social capital into account and analyzing the attenuation of the
      logit after the introduction of social participation, trust and their combination
      in the models. METHODS: In 2008 a cross-sectional public health survey was
      conducted in southern Sweden with a postal questionnaire with 28,198 participants
      aged 18-80 (55% participation rate). This study was restricted to 24,348
      participants without internally missing values on all included variables.
      Associations between sexual orientation and tobacco smoking were analyzed with
      logistic regression analysis. RESULTS: Overall, 11.9% of the men and 14.8% of the
      women were daily tobacco smokers. Higher and almost unaltered odds ratios of
      daily smoking compared to heterosexuals were observed for bisexual men and women,
      and for homosexual men throughout the analyses. The odds ratios of daily smoking
      among homosexual women were not significant. Only for the "other" sexual
      orientation group the odds ratios of daily smoking were reduced to not
      significant levels among both men and women, with a corresponding 54% attenuation
      of the logit in the "other" group among men and 31.5% among women after the
      inclusion of social participation and trust. In addition, only the "other" sexual
      orientation group had higher odds ratios of low participation than heterosexuals.
      CONCLUSIONS: Bisexual men and women and homosexual men, but not homosexual women,
      are daily smokers to a higher extent than heterosexuals. Only for the "other"
      sexual orientation group the odds ratios of daily smoking were reduced to not
      significant levels after adjustments for covariates including trust and social
      participation.

PMID- 24903893
TI  - Experiencing challenges when implementing active management of third stage of
      labor (AMTSL): a qualitative study with midwives in Accra, Ghana.
AB  - BACKGROUND: Post-partum hemorrhage (PPH) is the major cause of maternal mortality
      in Ghana and worldwide. Active management of the third stage of labor (AMTSL) is
      a globally recommended three-step method that in clinical trials has been proven
      effective in prevention of PPH. The AMTSL guidelines were introduced in 2003,
      modified in 2006, and has been part of the national guidelines in Ghana since
      2008. In 2012, the guidelines were modified a second time. Despite its positive
      effects on the incidence of PPH, the level of adherence to the guidelines seems
      to be low in the studied area. This appears to be a problem shared by several
      countries in the region. An in-depth understanding of midwives' experiences about
      AMTSL is important as it can provide a basis for further interventions in order
      to reach a higher grade of implementation. METHODS: Twelve in-depth interviews
      were conducted with labor ward midwives who all had previous training in AMTSL.
      The interviews took place in 2011 at three hospitals in Accra Metropolis and data
      was analyzed using qualitative latent content analysis. RESULTS: Our main finding
      was that the third step of AMTSL, uterine massage, was not implemented, even
      though the general attitude towards AMTSL was positive. Thus, despite regular
      training sessions, the midwives did not follow the Ghanaian national guidelines.
      Some contributing factors to difficulties in providing AMTSL to all women have
      been pointed out in this study, the most important being insufficiency in staff
      coverage. This led to a need for delegating certain steps of AMTSL to other
      health care staff, i.e. task shifting. The fact that the definition of AMTSL has
      changed several times since the introduction in 2003 might also be an aggravating
      factor. CONCLUSIONS: The results from this study highlight the need for
      continuous updates of national guidelines, extended educational interventions and
      recurrent controls of adherence to guidelines. AMTSL is an important tool in
      preventing PPH, however, it must be clarified how it should be used in countries
      with scarce resources. Also, considering the difficulties in implementing already
      existing guidelines, further modifications must be made with careful
      consideration.

PMID- 24903894
TI  - A tailor-made "tag-receptor" affinity pair for the purification of fusion
      proteins.
AB  - A novel affinity "tag-receptor" pair was developed as a generic platform for the
      purification of fusion proteins. The hexapeptide RKRKRK was selected as the
      affinity tag and fused to green fluorescent protein (GFP). The DNA fragments were
      designed, cloned in Pet-21c expression vector and expressed in E. coli host as
      soluble protein. A solid-phase combinatorial library based on the Ugi reaction
      was synthesized: 64 affinity ligands displaying complementary functionalities
      towards the designed tag. The library was screened by affinity chromatography in
      a 96-well format for binding to the RKRKRK-tagged GFP protein. Lead ligand A7C1
      was selected for the purification of RKRKRK fusion proteins. The affinity pair
      RKRKRK-tagged GFP with A7C1 emerged as a promising solution (Ka of 2.45*10(5)  M(
      1) ). The specificity of the ligand towards the tag was observed experimentally
      and theoretically through automated docking and molecular dynamics simulations. 

PMID- 24903895
TI  - Electrospinning of biomimetic scaffolds for tissue-engineered vascular grafts:
      threading the path.
AB  - Tissue-engineered vascular grafts (TEVGs) offer an alternative to synthetic
      grafts for the surgical treatment of atherosclerosis and congenital heart
      defects, and may improve graft patency and patient outcomes after implantation.
      Electrospinning is a versatile manufacturing process for the production of
      fibrous scaffolds. This review aims to investigate novel approaches undertaken to
      improve the design of electrospun scaffolds for TEVG development. The review
      describes how electrospinning can be adapted to produce aligned nanofibrous
      scaffolds used in vascular tissue engineering, while novel processes for improved
      performance of such scaffolds are examined and compared to evaluate their
      effectiveness and potential. By highlighting new drug delivery techniques and
      porogenic technologies, in addition to analyzing in vitro and in vivo testing of
      electrospun TEVGs, it is hoped that this review will provide guidance on how the
      next generation of electrospun vascular graft scaffolds will be designed and
      tested for the potential improvement of cardiovascular therapies. 

PMID- 24903896
TI  - Validation of a non-linear model of health.
AB  - PURPOSE: The purpose of this study was to evaluate the veracity of a
      theoretically derived model of health that describes a non-linear trajectory of
      health from birth to death with available population data sets. METHODS: The
      distribution of mortality by age is directly related to health at that age, thus
      health approximates 1/mortality. The inverse of available all-cause mortality
      data from various time periods and populations was used as proxy data to compare
      with the theoretically derived non-linear health model predictions, using both
      qualitative approaches and quantitative one-sample Kolmogorov-Smirnov analysis
      with Monte Carlo simulation. RESULTS: The mortality data's inverse resembles a
      log-normal distribution as predicted by the proposed health model. The curves
      have identical slopes from birth and follow a logarithmic decline from peak
      health in young adulthood. A majority of the sampled populations had a good to
      excellent quantitative fit to a log-normal distribution, supporting the
      underlying model assumptions. Post hoc manipulation showed the model predictions
      to be stable. CONCLUSIONS: This is a first theory of health to be validated by
      proxy data, namely the inverse of all-cause mortality. This non-linear model,
      derived from the notion of the interaction of physical, environmental, mental,
      emotional, social and sense-making domains of health, gives physicians a more
      rigorous basis to direct health care services and resources away from disease
      focused elder care towards broad-based biopsychosocial interventions earlier in
      life.

PMID- 24903897
TI  - A novel L1340P mutation in the ANK1 gene is associated with hereditary
      spherocytosis?

PMID- 24903898
TI  - Seizure frequency and patient-centered outcome assessment in epilepsy.
AB  - OBJECTIVE: Seizure frequency represents a commonly assessed epilepsy status, but
      in the context of the growing trend toward patient-centered care, we examined the
      adequacy of seizure frequency as a measure of epilepsy status as perceived by the
      patient. METHODS: Between 2006 and 2008, we assessed seizure frequency, mood, and
      preference-based health-related quality of life (HRQOL) measured with the visual
      analog scale metric in 182 adult patients sampled consecutively. Using
      nonparametric tests and Monte Carlo computer simulations, we analyzed the
      relationship between preference-based HRQOL and seizure frequency, and using
      regression analyses, we tested for significant predictors of preference-based
      HRQOL. RESULTS: Only patients who had been seizure-free for >1 year had
      significantly higher preference-based HRQOL (p < 0.0001) than those who
      experienced any recurrent seizure, regardless of their seizure frequency. Among
      patients with recurrent seizures, preference-based HRQOL and seizure frequency
      were not monotonically, linearly related. For patients with similar seizure
      frequency, preference-based HRQOL varied substantially with large overlaps in
      preference-based HRQOL across different seizure frequency categories. The Monte
      Carlo simulation found that seizure frequency was a poor predictor of preference
      based HRQOL about one third of the time. The presence of depressive symptoms was
      an independent predictor of preference-based HRQOL measure, accounting for 33.5%
      of the variation in scores between patients. SIGNIFICANCE: Our findings highlight
      the importance of attaining complete seizure freedom and the substantial
      variation in preference-based HRQOL among patients with similar seizure
      frequencies. To improve assessment of patient-centered outcomes in epilepsy, we
      encourage adding direct measurement of preference-based HRQOL into clinical care.

PMID- 24903899
TI  - Simultaneous determination of three dipeptides (JBP485, Gly-Sar and JBP923) in
      the cell lysates by liquid chromatography-tandem mass spectrometry: application
      to identify the function of the PEPT1 transfected cell.
AB  - A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the simultaneous determination of JBP485, Gly-Sar and JBP923 in the
      cell lysates using methanol as a deproteinization solvent was developed and
      validated. Detection was performed by turbo ionspray ionization in multiple
      reaction monitoring mode using the transitions of m/z 147.1 -> m/z 90.1 for Gly
      Sar, m/z 201.1 -> m/z 86.1 for JBP485, m/z 219.1 -> m/z 86.1 for JBP923 and m/z
      152.0 -> m/z 110.0 for paracetamol (internal standard). The analytes were
      separated on a Hypersil ODS C18 HPLC column using isocratic elution mode with a
      mobile phase containing 0.1% formic acid in water-methanol (97:3, v/v) at a flow
      rate of 0.2 mL/min. The calibration curves were demonstrated to be linear over
      the concentration range of 5.00-5000 nm with coefficient of 0.9968 for Gly-Sar,
      0.9975 for JBP485 and 0.9952 for JBP923. The intra- and inter-day precisions were
      <10.2% for each quality contro; level, and the accuracy was within +/-5.6% for
      each analyte. The matrix effect, the extraction recovery and stabilities of LC
      MS/MS analysis were also investigated. This validated method was successfully
      applied to the simultaneous determination of JBP485, Gly-Sar and JBP923 in the
      cell lysates for identification of stably transfected HeLa cells with human
      PEPT1.

PMID- 24903900
TI  - Imaging flow cytometry elucidates limitations of microparticle analysis by
      conventional flow cytometry.
AB  - Microparticles (MPs) are submicron vesicles released from cell membranes in
      response to activation, cell injury, or apoptosis. The clinical importance of MPs
      has become increasingly recognized, although no standardized method exists for
      their measurement. Flow cytometry (FCM) is the most commonly used technique,
      however, because of the small size of MPs, and the limitations of current FCM
      instrumentation, accurate identification is compromised by this methodology. We
      decided to investigate whether the use of FCM combined with imaging, such as is
      possible with the ImagestreamX imaging FC (ISX), would be a more sensitive
      approach to characterizing MPs. Combining FCM with imaging eliminates some of the
      limitations demonstrated by conventional FCM, whereas also providing
      morphological confirmation and the ability to distinguish true single events from
      aggregates and cell debris. The detection limit of standard nonspecialized FCM is
      suboptimal when compared to ISX. Evaluating MPs below 0.200 um and sizing remain
      a challenge as some MPs remain below the detection limit of ISX. Standardized
      calibrators, that more closely reflect the physical characteristics of MPs, need
      further development.

PMID- 24903901
TI  - Inflammation and glycemic tolerance status in pregnancy: the role of maternal
      adiposity.
AB  - BACKGROUND/AIMS: Although the association between inflammation and insulin
      resistance is well known, the data related to the role of inflammation in
      gestational diabetes mellitus (GDM) are conflicting. The aim of this study was to
      investigate the association of several inflammatory mediators with the glycemic
      status in pregnancy. METHODS: Leukocyte count, ferritin, C-reactive protein
      (CRP), fibrinogen and interleukin-6 levels were measured in 70 patients with
      normal glucose tolerance, in 57 patients with impaired glucose tolerance and in
      35 patients with GDM as determined based on 50-gram oral glucose tolerance test
      (OGTT) and 100-gram OGTT results. RESULTS: A significant difference among the
      groups was seen only with regard to CRP and fibrinogen levels; however, no
      significant differences were observed after adjustment for body mass index (BMI).
      CRP was found to be strongly associated with current BMI in all three groups.
      CONCLUSION: Maternal serum levels of inflammatory mediators are not related to
      GDM at the time of the glucose challenge test in the late second or early third
      trimester. The significant difference in the levels of CRP in different strata of
      glycemic tolerance was not observed after adjustment for BMI. Adiposity may have
      a central role in GDM, causing an inflammatory response.

PMID- 24903902
TI  - GMC's planned study into GP selection scheme's value in predicting MRCGP
      performance is flawed.

PMID- 24903903
TI  - Pneumothorax after endobronchial valve treatment: no drain, no gain?

PMID- 24903905
TI  - TBX21 participates in innate immune response by regulating Toll-like receptor 2
      expression in Streptococcus pneumoniae infections.
AB  - Nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) plays an
      important role in the development of invasive diseases, and is also critically
      involved in setting up respiratory bacterial and viral infections. We previously
      reported that pneumococcus, one of the commonly carried bacteria in the
      nasopharynx, regulates non-typeable Haemophilus influenzae-induced inflammation
      by upregulating the expression of Toll-like receptor 2 (TLR2). However, the
      underlying molecular mechanisms by which TLR2 expression is regulated during
      pneumococcal infections have not yet been well characterized. TBX21 is an
      important transcription factor of adaptive immunity, but there is an increasing
      body of evidence pointing to a role in regulating innate immunity. The expression
      of TBX21 was reported in epithelial cells, but the expression and role of TBX21
      in respiratory epithelium, especially for regulating TLR2, has not yet been
      studied. In this study, we found that pneumococcus upregulates TBX21 expression
      in the respiratory epithelium. The effect of pneumococcus on TBX21 expression was
      dependent on its cytoplasmic toxin, pneumolysin. In addition, epithelial TBX21
      expression was not regulated by the gram-negative bacterium non-typeable
      Haemophilus influenzae, peptidoglycan or endotoxin. Deficiency of TBX21 in mice
      or knocking down TBX21 in epithelial cells suppressed pneumococcus-induced TLR2
      expression, but not that of TLR4 or TLR9. These results indicate that the
      adaptive immune regulator TBX21 participates in regulating innate immune
      responses, through regulation of TLR2 expression during pneumococcal infections. 

PMID- 24903904
TI  - Survival prediction model of children with diffuse intrinsic pontine glioma based
      on clinical and radiological criteria.
AB  - BACKGROUND: Although diffuse intrinsic pontine glioma (DIPG) carries the worst
      prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG
      are sparse. To control for confounding variables in DIPG studies, which generally
      include relatively small patient numbers, a survival prediction tool is needed.
      METHODS: A multicenter retrospective cohort study was performed in the
      Netherlands, the UK, and Germany with central review of clinical data and MRI
      scans of children with DIPG. Cox proportional hazards with backward regression
      was used to select prognostic variables (P < .05) to predict the accumulated 12
      month risk of death. These predictors were transformed into a practical risk
      score. The model's performance was validated by bootstrapping techniques.
      RESULTS: A total of 316 patients were included. The median overall survival was
      10 months. Multivariate Cox analysis yielded 5 prognostic variables of which the
      coefficients were included in the risk score. Age <=3 years, longer symptom
      duration at diagnosis, and use of oral and intravenous chemotherapy were
      favorable predictors, while ring enhancement on MRI at diagnosis was an
      unfavorable predictor. With increasing risk score categories, overall survival
      decreased significantly. The model can distinguish between patients with very
      short, average, and increased overall survival (medians of 7.0, 9.7, and 13.7 mo,
      respectively). The area under the receiver operating characteristic curve was
      0.68. CONCLUSIONS: We developed a DIPG survival prediction tool that can be used
      to predict the outcome of patients and for stratification in trials. Validation
      of the model is needed in a prospective cohort.

PMID- 24903906
TI  - Reply to the letter by Kapoor entitled 'Emerging new markers of stroke risk and
      prognosis'.

PMID- 24903907
TI  - Cytokine-induced slowing of STAT3 nuclear import; faster basal trafficking of the
      STAT3beta isoform.
AB  - The STAT3 signal transducer and activator of transcription is a key mediator of
      gene transcription in response to cytokines such as oncostatin M (OSM). We
      performed direct live cell imaging of GFP-tagged STAT3 proteins for the first
      time, showing transient relocalization of STAT3alpha to the nucleus following OSM
      exposure, in contrast to sustained nuclear relocalization of the shorter
      STAT3beta spliceform. To explore this further, we applied fluorescence recovery
      after photobleaching (FRAP) to determine the nuclear import kinetics of
      STAT3alpha and beta, as well as of a C-terminal truncation derivative STAT3DeltaC
      comprising only the sequence shared by the spliceforms, in the absence or
      presence of OSM. The rates of basal nuclear import for STAT3beta and STAT3DeltaC
      were significantly faster than those for STAT3alpha. Strikingly, OSM slowed the
      import rates of all the three STAT3 proteins, whereas the import rates of GFP
      alone or a classical importin-mediated cargo were unaffected, with analysis of
      Y705F mutant derivatives for all the three STAT3 constructs, or of a S727A mutant
      within the unique C-terminus of STAT3alpha, reinforcing the contribution of
      specific phosphorylation to the cytokine-stimulated changes. The results
      introduce a new paradigm where cytokine treatment prolongs nuclear retention
      simultaneous with decreasing rather than increasing the rate of nuclear import. 

PMID- 24903908
TI  - Handgrip strength does not represent an appropriate measure to evaluate changes
      in muscle strength during an exercise intervention program in frail older people.
AB  - INTRODUCTION: Although handgrip strength is considered a strong predictor of
      negative health outcomes, it is unclear whether handgrip strength represents a
      useful measure to evaluate changes in muscle strength following resistance-type
      exercise training in older people. We assessed whether measuring handgrip
      strength provides proper insight in the efficacy of resistance-type exercise
      training to increase muscle mass, strength, and physical performance in frail
      older people. METHODS: Prefrail and frail older people (>= 65 y) were either
      conducting a 24-week resistance-type exercise training or no exercise training.
      Before, during, and after the intervention, handgrip strength (JAMAR), lean body
      mass (DXA), leg strength (1-RM), and physical performance (SPPB) were assessed.
      RESULTS: Handgrip strength correlated with appendicular lean mass (r = 0.68; p <
      .001) and leg strength (r = 0.67; p < .001). After 24 weeks of whole body
      resistance-type exercise training, leg extension strength improved significantly
      better when compared with the control group (57 +/- 2-78 +/- 3 kg vs 57 +/- 3-65
      +/- 3 kg: p < .001). Moreover, physical performance improved significantly more
      in the exercise group (8.0 +/- 0.4-9.3 +/- 0.4 points) when compared with the
      control group (8.3 +/- 0.4-8.9 +/- 0.4 points: p < .05). These positive changes
      were not accompanied with any significant changes in handgrip strength (26.3 +/-
      1.2-27.6 +/- 1.2 kg in the exercise group vs 26.6 +/- 1.2-26.3 +/- 1.3 kg in the
      control group: p = .71). CONCLUSION: Although handgrip strength strongly
      correlates with muscle mass and leg strength in frail older people, handgrip
      strength does not provide a valid means to evaluate the efficacy of exercise
      intervention programs to increase muscle mass or strength in an older population.

PMID- 24903909
TI  - Rate of manual leukocyte differentials in dog, cat and horse blood samples using
      ADVIA 120 cytograms.
AB  - BACKGROUND: Modern automated haematology instruments are capable of performing
      leukocyte differentials faster, cheaper and with a higher precision than the
      traditional 100-cell manual differential count. Thus, in human laboratories,
      criteria are defined for performing a manual review of the blood smear resulting
      in a marked reduction of manual differential counts. While common in human
      laboratories, this approach to reducing the number of manual differentials in
      veterinary laboratories is still not commonly performed. Thus, our aim was to
      determine the rate and causes of manual leukocyte differentials in a university
      clinical pathology laboratory using the automated laser-based haematology
      analyser ADVIA 120. Overall, 14,953 complete blood cell counts from dogs, cats
      and horses were reviewed. Manual leukocyte differentials were requested if
      abnormal ADVIA peroxidase and baso cytograms were detected (i.e. suspicion of
      left shift or atypical lymphocytes/blasts, inappropriate separation of cell
      populations). RESULTS: In 21% of canine, 32% of feline and 20% of equine samples,
      a manual differential was requested. Indistinct separation of the cell population
      was present in 10% to 15% of the cases. Depending on the species, atypical
      lymphocytes were suspected in 2% to 12%, left shift in 13% to 25% and suspicion
      of blasts was present in less than 0.4% of the cases. CONCLUSIONS: The obtained
      results are comparable to those published for human medicine and the rate of
      manual differentiation could be markedly reduced in veterinary laboratories if
      microscopic examination was used as a validation procedure rather than as a
      reflexive substitute for automated differentiation.

PMID- 24903910
TI  - Allopurinol as a kidney-protective, cardioprotective, and antihypertensive agent:
      hype or reality?
AB  - Numerous experimental and clinical studies suggest that uric acid might have
      pathobiologic implications in the development and progression of hypertension,
      kidney disease, and coronary heart disease, among others, resulting in renewed
      interest in uric acid as a potential pathogenic mediator in these clinical
      conditions. Despite encouraging animal studies showing beneficial roles of
      allopurinol, clinical studies and randomized controlled trials remain scarce,
      and, despite available clinical evidence supporting a therapeutic role for
      allopurinol, multiple issues remain before routine use of allopurinol can be
      recommended for use in patients with hyperuricemia and hypertension, kidney
      disease, or coronary heart disease. These include a need for more robust clinical
      trial data that evaluate efficacy on hard clinical outcomes, optimal dose,
      duration of treatment, and the potential for serious allergic reactions. In this
      article we review the current available evidence describing the effects of
      allopurinol in hypertension, kidney disease, and coronary heart disease,
      highlighting unresolved issues surrounding allopurinol use for uric acid lowering
      in individuals without gout.

PMID- 24903911
TI  - Regulator of G protein signaling transcript expression in human neural progenitor
      differentiation: R7 subfamily regulation by DNA methylation.
AB  - G protein-coupled receptors (GPCRs) and their ligands are critical regulators of
      neural progenitor differentiation, and GPCR signaling pathways are regulated by
      regulator of G protein signaling (RGS) proteins. RGS protein expression is
      dynamically regulated, and we have recently described the epigenetic regulation
      of RGS transcript expression. Given the potential of RGS proteins to regulate
      GPCR signaling and the established role of epigenetic regulation in progenitor
      differentiation, we explored the impact of epigenetic regulation of RGS
      transcripts during in vitro differentiation of human neural progenitors. Here, we
      demonstrate robust upregulation of the RGS transcripts RGS4, RGS5, RGS6, RGS7,
      and RGS11 during neuronal differentiation, while DNA methyltransferase (DNMT) and
      histone deacetylase enzyme expression is suppressed during differentiation.
      Transcripts encoding R7 subfamily RGS proteins and the R7-binding partners R7BP
      and R9AP showed the greatest upregulation. Further, we showed that direct
      pharmacological inhibition of DNMT activity enhances expression of RGS2, RGS4,
      RGS5, RGS6, RGS7, RGS8, RGS9L, RGS10, and RGS14 as well as R7BP and R9AP
      transcripts in progenitors, consistent with regulation by DNMTs. Our results
      reveal marked upregulation of RGS expression during neuronal differentiation and
      suggest that decreased expression of DNMT enzymes during differentiation
      contributes to upregulation.

PMID- 24903912
TI  - Neutrophils: bugging transplantation.

PMID- 24903913
TI  - Microbiota: the liver debugs the system.

PMID- 24903915
TI  - Highly sensitive in situ monitoring of catalytic reactions by surface enhancement
      Raman spectroscopy on multifunctional Fe3O4/C/Au NPs.
AB  - In this study, multifunctional Fe3O4/C/Au nanoparticles (NPs), which
      catalytically integrated active small Au NPs with surface-enhanced Raman
      scattering (SERS) active large Au NPs, were fabricated via a facile method and
      employed for the in situ SERS monitoring of a catalytic reaction of p
      nitrothiophenol (p-NTP) to p-aminothiophenol (p-ATP). In addition, the effect of
      magnet power was tested and it was demonstrated that the SERS intensity of the
      reaction system was stronger, and the reaction proceeded more smoothly because
      more hot spots existed and remained the same in the magnetic field; hence, the
      catalytic rate could be determined.

PMID- 24903916
TI  - Extraction of cochlear non-linearities with the bispectral analysis. An
      application to TEOAEs in styrene-exposed workers.

PMID- 24903917
TI  - New approach to measure cutaneous microvascular function: an improved test of NO
      mediated vasodilation by thermal hyperemia.
AB  - Cutaneous hyperemia in response to rapid skin local heating to 42 degrees C has
      been used extensively to assess microvascular function. However, the response is
      dependent on both nitric oxide (NO) and endothelial-derived hyperpolarizing
      factors (EDHFs), and increases cutaneous vascular conductance (CVC) to ~90-95%
      maximum in healthy subjects, preventing the study of potential means to improve
      cutaneous function. We sought to identify an improved protocol for isolating NO
      dependent dilation. We compared nine heating protocols (combinations of three
      target temperatures: 36 degrees C, 39 degrees C, and 42 degrees C, and three
      rates of heating: 0.1 degrees C/s, 0.1 degrees C/10 s, 0.1 degrees C/min) in
      order to select two protocols to study in more depth (protocol 1; N = 6). Then,
      CVC was measured at four microdialysis sites receiving: 1) lactated Ringer
      solution (Control), 2) 50-mM tetraethylammonium (TEA) to inhibit EDHFs, 3) 20-mM
      nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase, and 4) TEA+L-NAME,
      in response to local heating either to 39 degrees C at 0.1 degrees C/s (protocol
      2; N = 10) or 42 degrees C at 0.1 degrees C/min (protocol 3; N = 8). Rapid
      heating to 39 degrees C increased CVC to 43.1 +/- 5.2%CVCmax (Control), which was
      attenuated by L-NAME (11.4 +/- 2.8%CVCmax; P < 0.001) such that 82.8 +/- 4.2% of
      the plateau was attributable to NO. During gradual heating, 81.5 +/- 3.3% of
      vasodilation was attributable to NO at 40 degrees C, but at 42 degrees C only
      32.7 +/- 7.8% of vasodilation was attributable to NO. TEA+L-NAME attenuated CVC
      beyond L-NAME at temperatures >40 degrees C (43.4 +/- 4.5%CVCmax at 42 degrees C,
      P < 0.001 vs. L-NAME), suggesting a role of EDHFs at higher temperatures. Our
      findings suggest local heating to 39 degrees C offers an improved approach for
      isolating NO-dependent dilation and/or assessing perturbations that may improve
      microvascular function. 

PMID- 24903914
TI  - Mast cell secretory granules: armed for battle.
AB  - Mast cells are important effector cells of the immune system and recent studies
      show that they have immunomodulatory roles in diverse processes in both health
      and disease. Mast cells are distinguished by their high content of electron-dense
      secretory granules, which are filled with large amounts of preformed and pre
      activated immunomodulatory compounds. When appropriately activated, mast cells
      undergo degranulation, a process by which these preformed granule compounds are
      rapidly released into the surroundings. In many cases, the effects that mast
      cells have on an immune response are closely associated with the biological
      actions of the granule compounds that they release, as exemplified by the recent
      studies showing that mast cell granule proteases account for many of the
      protective and detrimental effects of mast cells in various inflammatory
      settings. In this Review, we discuss the current knowledge of mast cell secretory
      granules. 

PMID- 24903918
TI  - Pulmonary ventilation defects in older never-smokers.
AB  - Hyperpolarized (3)He MRI previously revealed spatially persistent ventilation
      defects in healthy, older compared with healthy, younger never-smokers. To
      understand better the physiological consequences and potential relevance of (3)He
      MRI ventilation defects, we evaluated (3)He-MRI ventilation-defect percent (VDP)
      and the effect of deep inspiration (DI) and salbutamol on VDP in older never
      smokers. To identify the potential determinants of ventilation defects in these
      subjects, we evaluated dyspnea, pulmonary function, and cardiopulmonary exercise
      test (CPET) measurements, as well as occupational and second-hand smoke exposure.
      Fifty-two never-smokers (71 +/- 6 yr) with no history of chronic respiratory
      disease were evaluated. During a single visit, pulmonary function tests, CPET,
      and (3)He MRI were performed and the Burden of Obstructive Lung Disease
      questionnaire administered. For eight of 52 subjects, there was spirometry
      evidence of airflow limitation (Global Initiative for Chronic Obstructive Lung
      Disease-Unclassified, I, and II), and occupational exposure was reported in 13 of
      52 subjects. In 13 of 52 (25%) subjects, there were no ventilation defects and in
      39 of 52 (75%) subjects, ventilation defects were observed. For those subjects
      with ventilation defects, six of 39 showed a VDP response to DI/salbutamol.
      Ventilation heterogeneity and VDP were significantly greater, and forced
      expiratory volume in 1 s (FEV1)/forced vital capacity was significantly lower (P
      < 0.05) for subjects with ventilation defects with a response to DI/salbutamol
      than subjects with ventilation defects without a response to DI/salbutamol and
      subjects without ventilation defects. In a step-wise, forward multivariate model,
      FEV1, inspiratory capacity, and airway resistance significantly predicted VDP
      (R(2) = 0.45, P < 0.001). In conclusion, most never-smokers had normal spirometry
      and peripheral ventilation defects not reversed by DI/salbutamol; such
      ventilation defects were likely related to irreversible airway narrowing/collapse
      but not to dyspnea and decreased exercise capacity. 

PMID- 24903919
TI  - Blood flow does not redistribute from respiratory to leg muscles during exercise
      breathing heliox or oxygen in COPD.
AB  - In patients with chronic obstructive pulmonary disease (COPD), one of the
      proposed mechanisms for improving exercise tolerance, when work of breathing is
      experimentally reduced, is redistribution of blood flow from the respiratory to
      locomotor muscles. Accordingly, we investigated whether exercise capacity is
      improved on the basis of blood flow redistribution during exercise while subjects
      are breathing heliox (designed to primarily reduce the mechanical work of
      breathing) and during exercise with oxygen supplementation (designed to primarily
      enhance systemic oxygen delivery but also to reduce mechanical work of
      breathing). Intercostal, abdominal, and vastus lateralis muscle perfusion were
      simultaneously measured in 10 patients with COPD (forced expiratory volume in 1
      s: 46 +/- 12% predicted) by near-infrared spectroscopy using indocyanine green
      dye. Measurements were performed during constant-load exercise at 75% of peak
      capacity to exhaustion while subjects breathed room air and, then at the same
      workload, breathed either normoxic heliox (helium 79% and oxygen 21%) or 100%
      oxygen, the latter two in balanced order. Times to exhaustion while breathing
      heliox and oxygen did not differ (659 +/- 42 s with heliox and 696 +/- 48 s with
      100% O2), but both exceeded that on room air (406 +/- 36 s, P < 0.001). At
      exhaustion, intercostal and abdominal muscle blood flow during heliox (9.5 +/-
      0.6 and 8.0 +/- 0.7 ml . min(-1).100 g(-1), respectively) was greater compared
      with room air (6.8 +/- 0.5 and 6.0 +/- 0.5 ml.min(-1).100 g., respectively; P <
      0.05), whereas neither intercostal nor abdominal muscle blood flow differed
      between oxygen and air breathing. Quadriceps muscle blood flow was also greater
      with heliox compared with room air (30.2 +/- 4.1 vs. 25.4 +/- 2.9 ml.min(-1).100
      g(-1); P < 0.01) but did not differ between air and oxygen breathing. Although
      our findings confirm that reducing the burden on respiration by heliox or oxygen
      breathing prolongs time to exhaustion (at 75% of maximal capacity) in patients
      with COPD, they do not support the hypothesis that redistribution of blood flow
      from the respiratory to locomotor muscles is the explanation. 

PMID- 24903920
TI  - Effects of resistance training on tendon mechanical properties and rapid force
      production in prepubertal children.
AB  - Children develop lower levels of muscle force, and at slower rates, than adults.
      Although strength training in children is expected to reduce this differential, a
      synchronous adaptation in the tendon must be achieved to ensure forces continue
      to be transmitted to the skeleton with efficiency while minimizing the risk of
      strain-related tendon injury. We hypothesized that resistance training (RT) would
      alter tendon mechanical properties in children concomitantly with changes in
      force production characteristics. Twenty prepubertal children (age 8.9 +/- 0.3
      yr) were equally divided into control (nontraining) and experimental (training)
      groups. The training group completed a 10-wk RT intervention consisting of 2-3
      sets of 8-15 plantar flexion contractions performed twice weekly on a recumbent
      calf-raise machine. Achilles tendon properties (cross-sectional area, elongation,
      stress, strain, stiffness, and Young's modulus), electromechanical delay (EMD;
      time between the onset of muscle activity and force), rate of force development
      (RFD; slope of the force-time curve), and rate of electromyographic (EMG)
      increase (REI; slope of the EMG time curve) were measured before and after RT.
      Tendon stiffness and Young's modulus increased significantly after RT in the
      experimental group only (~29% and ~25%, respectively); all other tendon
      properties were not significantly altered, although there were mean decreases in
      both peak tendon strain and strain at a given force level (14% and 24%,
      respectively; not significant) which may have implications for tendon injury risk
      and muscle fiber mechanics. A decrease of ~13% in EMD was found after RT for the
      experimental group, which paralleled the increase in tendon stiffness (r = 
      0.59); however, RFD and REI were unchanged. The present data show that the
      Achilles tendon adapts to RT in prepubertal children and is paralleled by a
      change in EMD, although the magnitude of this change did not appear to be
      sufficient to influence RFD. These findings are of importance within the context
      of the efficiency and execution of movement. 

PMID- 24903922
TI  - E-wave generated intraventricular diastolic vortex to L-wave relation: model
      based prediction with in vivo validation.
AB  - The Doppler echocardiographic E-wave is generated when the left ventricle's
      suction pump attribute initiates transmitral flow. In some subjects E-waves are
      accompanied by L-waves, the occurrence of which has been correlated with
      diastolic dysfunction. The mechanisms for L-wave generation have not been fully
      elucidated. We propose that the recirculating diastolic intraventricular vortex
      ring generates L-waves and based on this mechanism, we predict the presence of L
      waves in the right ventricle (RV). We imaged intraventricular flow using Doppler
      echocardiography and phase-contrast magnetic resonance imaging (PC-MRI) in 10
      healthy volunteers. L-waves were recorded in all subjects, with highest
      velocities measured typically 2 cm below the annulus. Fifty-five percent of
      cardiac cycles (189 of 345) had L-waves. Color M-mode images eliminated mid
      diastolic transmitral flow as the cause of the observed L-waves. Three
      dimensional intraventricular flow patterns were imaged via PC-MRI and
      independently validated our hypothesis. Additionally as predicted, L-waves were
      observed in the RV, by both echocardiography and PC-MRI. The re-entry of the E
      wave-generated vortex ring flow through a suitably located echo sample volume can
      be imaged as the L-wave. These waves are a general feature and a direct
      consequence of LV and RV diastolic fluid mechanics. 

PMID- 24903921
TI  - Interrelationship of CB1R and OBR pathways in regulation of metabolic,
      neuroendocrine, and behavioral responses to food restriction and voluntary wheel
      running.
AB  - We hypothesized the cannabinoid-1 receptor and leptin receptor (ObR) operate
      synergistically to modulate metabolic, neuroendocrine, and behavioral responses
      of animals exposed to a survival challenge (food restriction and wheel running).
      Obese-prone (OP) JCR:LA-cp rats, lacking functional ObR, and lean-prone (LP)
      JCR:LA-cp rats (intact ObR) were assigned to OP-C and LP-C (control) or CBR1
      antagonized (SR141716, 10 mg/kg body wt in food) OP-A and LP-A groups. After 32
      days, all rats were exposed to 1.5-h daily meals without the drug and 22.5-h
      voluntary wheel running, a survival challenge that normally culminates in
      activity-based anorexia (ABA). Rats were removed from the ABA protocol when body
      weight reached 75% of entry weight (starvation criterion) or after 14 days
      (survival criterion). LP-A rats starved faster (6.44 +/- 0.24 days) than LP-C
      animals (8.00 +/- 0.29 days); all OP rats survived the ABA challenge. LP-A rats
      lost weight faster than animals in all other groups (P < 0.001). Consistent with
      the starvation results, LP-A rats increased the rate of wheel running more
      rapidly than LP-C rats (P = 0.001), with no difference in hypothalamic and
      primary neural reward serotonin levels. In contrast, OP-A rats showed suppression
      of wheel running compared with the OP-C group (days 6-14 of ABA challenge, P <
      0.001) and decreased hypothalamic and neural reward serotonin levels (P < 0.01).
      Thus there is an interrelationship between cannabinoid-1 receptor and ObR
      pathways in regulation of energy balance and physical activity. Effective
      clinical measures to prevent and treat a variety of disorders will require
      understanding of the mechanisms underlying these effects.

PMID- 24903923
TI  - Two years of combined high-intensity physical training and heat acclimatization
      affect lymphocyte and serum HSP70 in purebred military working dogs.
AB  - Military working dogs in hot countries undergo exercise training at high ambient
      temperatures for at least 9 mo annually. Physiological adaptations to these harsh
      conditions have been extensively studied; however, studies focusing on the
      underlying molecular adaptations are limited. In the current study, military
      working dogs were chosen as a model to examine the effects of superimposing
      endurance exercise on seasonal acclimatization to environmental heat stress. The
      lymphocyte HSP70 profile and extracellular HSP70 were studied in tandem with
      physiological performance in the dogs from their recruitment for the following 2
      yr. Aerobic power and heat shock proteins were measured at the end of each
      summer, with physical performance tests (PPTs) in an acclimatized room (22
      degrees C). The study shows that together with a profound enhancement of aerobic
      power and physical performance, hsp72 mRNA induction immediately post-PPT and 45
      min later, progressively increased throughout the study period (relative change
      in median lymphocyte hsp72 mRNA first PPT, 4.22 and 12.82; second PPT, 17.19 and
      109.05, respectively), whereas induction of HSP72 protein was stable. These
      responses suggest that cellular/molecular adaptive tools for maintaining HSP72
      homeostasis exist. There was also a significant rise in basal and peak median
      optical density extracellular HSP at the end of each exercise test (first PPT,
      0.13 and 0.15; second PPT, 1.04 and 1.52, respectively). The relationship between
      these enhancements and improved aerobic power capacity is not yet fully
      understood.

PMID- 24903924
TI  - Caregiver burden in patients with Parkinson disease undergoing deep brain
      stimulation: an exploratory analysis.
AB  - BACKGROUND: Little is known about caregiver burden in Parkinson disease (PD)
      patients undergoing brain stimulation (DBS) surgery. OBJECTIVE: The aim of this
      exploratory analysis was to evaluate whether caregiver burden improves after
      bilateral subthalamic nucleus (STN) DBS for PD patients and identify baseline
      factors associated with caregiver burden. METHODS: We analyzed the motor,
      cognitive and behavioral data of 12 PD patients (9 men/3 women) who underwent
      bilateral STN DBS and whose caregivers completed the Caregiver Burden Inventory
      (CBI) both before and approximately 6 months after bilateral STN DBS. RESULTS:
      Total CBI score did not change from baseline (17.8 +/- 10.7) to the 6 month
      evaluation (18.7 +/- 13.1), despite a 29% improvement in the MDS-UPDRS motor
      score (baseline 40.3 +/- 12.1 compared to 28.7 +/- 8.4 at 6 months, p = 0.01).
      Change in total CBI score did not correlate with change in MDS-UPDRS Parts I-IV
      or MoCA from baseline to 6 months. In post-hoc analyses looking at baseline
      characteristics that may correlate with caregiver burden, only the disinhibition
      subscore on the Frontal Systems Behavioral Scale correlated positively with the
      baseline total CBI score (rho = 0.763, p = 0.004). CONCLUSION: Caregiver burden
      for PD patients (as measured by the CBI) does not change 6 months after bilateral
      STN DBS, despite significant improvement in motor function. Only baseline
      behavioral problems, specifically disinhibition, correlated with higher baseline
      caregiver burden. Clinicians may need to better counsel patients on expectations
      for caregiver burden after DBS.

PMID- 24903925
TI  - Natural radioactivity in groundwater from the south-eastern Arabian Peninsula and
      environmental implications.
AB  - Groundwater is the most valuable resource in arid regions, and recognizing
      radiological criteria among other water quality parameters is essential for
      sustainable use. In the investigation presented here, gross-alpha and gross-beta
      were measured in groundwater samples collected in the south-eastern Arabian
      Peninsula, 67 wells in Unite Arab Emirates (UAE), as well as two wells and one
      spring in Oman. The results show a wide gross-alpha and gross-beta activities
      range in the groundwater samples that vary at 0.01~19.5 Bq/l and 0.13~6.6 Bq/l,
      respectively. The data show gross-beta and gross-alpha values below the WHO
      permissible limits for drinking water in the majority of the investigated samples
      except those in region 4 (Jabel Hafit and surroundings). No correlation between
      groundwater pH and the gross-alpha and gross-beta, while high temperatures
      probably enhance leaching of radionuclides from the aquifer body and thereby
      increase the radioactivity in the groundwater. This conclusion is also supported
      by the positive correlation between radioactivity and amount of total dissolved
      solid. Particular water purification technology and environmental impact
      assessments are essential for sustainable and secure use of the groundwater in
      regions that show radioactivity values far above the WHO permissible limit for
      drinking water.

PMID- 24903926
TI  - Children's awareness of alcohol sponsorship of sport in Ireland: Munster Rugby
      and the 2008 European Rugby Cup.
AB  - OBJECTIVES: Examined children's awareness of sport sponsorship in Ireland,
      focussing on the 2008 European Rugby Cup win by Munster Rugby. METHODS: Following
      the Munster Rugby win in 2008, a cross-sectional sample of 1,175 children (7-13
      years) in 11 National Schools in Ireland were asked which company sponsored "the
      cup that Munster won" and were then asked to name the product made by that
      company. RESULTS: Significantly higher level of awareness of the sponsor by
      children in Munster (69.9 %) to those outside Munster (21.5 %). No significant
      difference in the level of awareness of their product (alcohol) by location
      (inside Munster 75.9 %, outside Munster 83.6 %). CONCLUSIONS: These findings
      support the view for an immediate introduction of legislation banning the
      sponsorship of sport.

PMID- 24903927
TI  - Nothing is wrong with descriptive papers.

PMID- 24903928
TI  - Linezolid in the treatment of drug-resistant tuberculosis: the way forward?

PMID- 24903929
TI  - Distinguishing between pulmonary tuberculosis and non-tuberculous mycobacterial
      lung disease.

PMID- 24903930
TI  - Exhaled nitric oxide as a screening tool for occupational asthma.

PMID- 24903931
TI  - The first population-based national tuberculosis prevalence survey in Ethiopia,
      2010-2011.
AB  - SETTING: Tuberculosis (TB) remains a major public health problem in Ethiopia.
      OBJECTIVE: To determine the prevalence of pulmonary TB among the general adult
      population aged >=15 years in 2010-2011. METHOD A nationwide, cluster-sampled,
      stratified (urban/rural/pastoralist), cross-sectional survey was conducted in 85
      selected clusters. All consenting participants were screened for TB using: 1)
      chest X-ray (CXR) and 2) an interview to screen for symptoms suggestive of TB
      disease. RESULT: Of 51,667 eligible individuals, 46,697 (90%) participated in the
      survey and completed at least the screening interview. CXR was performed among
      46,548 (99.7%) participants. A total of 6080 (13%) participants were eligible for
      sputum examination. From the survey, it was estimated that in the national adult
      population 1) the prevalence of smear-positive TB was 108/100,000 (95%CI 73-143),
      and 2) that of bacteriologically confirmed TB was 277/100,000 (95%CI 208-347).
      CONCLUSION: We found that the TB burden was lower than previously thought, which
      may indicate better programme performance. However, a high proportion of TB among
      young persons suggests that TB is circulating in the community and that there is
      a need for more efforts to limit the spread of TB disease.

PMID- 24903932
TI  - Predictors of contact tracing completion and outcomes in tuberculosis: a 21-year
      retrospective cohort study.
AB  - SETTING: Birmingham, UK, 1990-2010. OBJECTIVE: To identify predictors in contacts
      for completion of screening and of a positive screening outcome, i.e., a
      diagnosis of latent tuberculous infection (LTBI) or active tuberculosis (TB).
      DESIGN: A retrospective cohort study of TB notifications for a European city.
      RESULTS: A total of 46,158 contacts were identified from 7365 index cases. Over
      the study period 17,471 (40.9%) failed to complete screening. Active TB or LTBI
      was diagnosed in 2220 (7.0%) contacts of cases of pulmonary TB (PTB) and in 222
      (2.7%) contacts of cases of extra-pulmonary TB (EPTB). The proportion of contacts
      offered LTBI treatment increased (P < 0.001) over the study period. Age,
      ethnicity, sex and use of interferon-gamma release assays (IGRA) were the most
      important predictors of screening completion, with working age adult males who
      were Black or from the Indian subcontinent least likely to complete. Age, smear
      positivity status of the index case and IGRA usage were the most important
      predictors of a positive screening outcome (active TB or LTBI diagnosed).
      CONCLUSION: Contact tracing of both PTB and EPTB index cases is useful for active
      case finding. The findings of this study can be used to target screening and
      improve the effectiveness and efficiency of local contact tracing programmes.

PMID- 24903933
TI  - Cost-effectiveness of rapid susceptibility testing against second-line drugs for
      tuberculosis.
AB  - BACKGROUND: Drug susceptibility testing (DST) against second-line tuberculosis
      drugs (SLDs) is essential for improving outcomes among multidrug-resistant (MDR-)
      and extensively drug-resistant tuberculosis (XDR-TB) cases. OBJECTIVE: To
      evaluate the potential cost-effectiveness of rapid DST for SLDs. DESIGN: We
      constructed a decision analysis model of Xpert MTB/RIF-based TB diagnosis in East
      and South-East Asia to compare culture-based DST vs. a hypothetical rapid SLD DST
      system for specimens resistant to rifampin. Our primary outcomes were the
      effectiveness and incremental cost-effectiveness of a rapid SLD DST assay
      relative to culture-based DST. RESULTS: For rapid SLD DST to be more effective
      than culture-based DST, treating individuals with pre-XDR/XDR-TB with a
      standardized MDR-TB regimen while awaiting culture-based DST must incur at least
      30% excess XDR-TB mortality (100% = treatment with first-line drugs); rapid SLD
      DST should attain an aggregate sensitivity and specificity for all pre-XDR/XDR
      mutations of 88% and 96%, respectively. The unit cost of the rapid SLD DST assay
      must approach that of culture to achieve common thresholds for cost-effectiveness
      in low-income countries. CONCLUSION: Rapid SLD DST has the potential to be cost
      effective, but must meet stringent criteria for accuracy and costs, and requires
      that standardized second-line treatment for pre-XDR/XDR-TB incur substantial
      excess mortality before the return of culture results.

PMID- 24903934
TI  - Survey of tuberculosis drug resistance among Tibetan refugees in India.
AB  - SETTING: Tuberculosis (TB) is a major health problem among Tibetans living in
      exile in India. Although drug-resistant TB is considered common in clinical
      practice, precise data are lacking. OBJECTIVE: To determine the proportion of
      drug-resistant cases among new and previously treated Tibetan TB patients.
      DESIGN: In a drug resistance survey in five Tibetan settlements in India, culture
      and drug susceptibility testing (DST) for first-line drugs were performed among
      all consecutive new and previously treated TB cases from April 2010 to September
      2011. DST against kanamycin (KM), ethionamide, para-aminosalicylic acid and
      ofloxacin (OFX) was performed on multidrug-resistant TB (MDR-TB) isolates.
      RESULTS: Of 307 patients enrolled in the study, 264 (193 new and 71 previously
      treated) were culture-positive and had DST available. All patients tested for the
      human immunodeficiency virus (n = 250) were negative. Among new TB cases, 14.5%
      had MDR-TB and 5.7% were isoniazid (INH) monoresistant. Among previously treated
      cases, 31.4% had MDR-TB and 12.7% were INH-monoresistant. Of the MDR-TB isolates,
      28.6% of new and 26.1% of previously treated cases were OFX-resistant, while 7.1%
      of new cases and 8.7% of previously treated cases were KM-resistant. Three
      patients had extensively drug-resistant TB. CONCLUSIONS: MDR-TB is common in new
      and previously treated Tibetans in India, who also show additional complex
      resistance patterns. Of particular concern is the high percentage of MDR-TB
      strains resistant to OFX, KM or both.

PMID- 24903935
TI  - Multidrug-resistant tuberculosis in the United Kingdom and Lithuania.
AB  - Rates of resistance to first- and second-line drugs in multidrug-resistant
      tuberculosis (MDR-TB) cases in the United Kingdom were studied during 2010-2012.
      The highest rates for ethambutol, pyrazinamide and aminoglycosides occurred among
      patients originating in Eastern Europe, of whom 47% were Lithuanian. Rates of
      resistance to kanamycin were significantly lower (P < 0.0001) in the Lithuanian
      National TB Register than among Lithuanian patients resident in the United
      Kingdom (5% vs. 78%). In 2010, the majority of UK patients of Eastern European
      origin were located within the London region, whereas in 2011 the majority were
      located outside this region, a significant change (P = 0.01). 

PMID- 24903936
TI  - Same-day light-emitting diode fluorescence microscopy for the diagnosis of
      tuberculosis in Chhattisgarh, India.
AB  - SETTING: Three medical college hospitals using light-emitting diode fluorescence
      microscopy (LED-FM) for diagnosing tuberculosis (TB) in Chhattisgarh, India.
      OBJECTIVES: To assess and compare the proportion of sputum smear-positive TB
      patients diagnosed through same-day microscopy (spot-spot) strategy or with the
      conventional (spot-morning) strategy. METHODS: During November 2012 - March 2013,
      all consecutively enrolled presumptive TB patients (aged >= 18 years) were
      requested to provide three specimens: two spot specimens collected 1 h apart on
      the first day and one early morning specimen the next day; these were stained
      using auramine-O and examined using LED-FM. RESULTS: Of 1716 (93% of total 1845)
      presumptive TB patients who provided all three specimens, 218 (13%) were smear
      positive: 200 (11.7%) by same-day microscopy and 217 (12.7%) by the conventional
      method (McNemar's chi(2) 13.5, df 1, P = 0.0002). Eighteen (8.3%) cases were
      missed by the same-day method. CONCLUSION: Although LED-FM is more sensitive to
      paucibacillary samples, 8% of smear-positive cases were missed using the same-day
      method. These findings indicate the need to revisit the global applicability of
      the current World Health Organization recommendation of switching to same-day
      diagnosis from the conventional policy.

PMID- 24903937
TI  - Cathelicidin and human beta-defensin 2 in bronchoalveolar lavage fluid of
      children with pulmonary tuberculosis.
AB  - BACKGROUND: The antimicrobial peptide cathelicidin LL-37/hCAP-18 and human beta
      defensins (hBD) are key factors in innate immune responses of the respiratory
      tract. OBJECTIVE: To determine LL-37 and hBD-2 concentrations in the
      bronchoalveolar lavage (BAL) fluid of paediatric patients (aged <16 years) with
      pulmonary tuberculosis (TB) and to compare these with concentrations in healthy
      children. METHODS: We measured peptide concentrations using an immunosorbent
      assay (ELISA). RESULTS Forty TB patients and 40 healthy controls were enrolled in
      the study (mean age 9.2 +/- 4.7 and 8.3 +/- 4.2 years, respectively, P = 0.97).
      The two groups exhibited no statistically significant difference in terms of sex,
      body mass index, relative weight or 25-hydroxyvitamin D levels. The mean BAL LL
      37 level of the TB group was significantly higher than that of the control group
      (0.95 +/- standard deviation [SD] 1.33 vs. 0.35 +/- SD 0.51 ng/ml, P = 0.01, t =
      2.54). The hBD-2 level was also higher in the TB group; however, the difference
      was not statistically significant (0.30 +/- SD 0.58 vs. 0.14 +/- SD 0.30 ng/ml, P
      = 0.11). There was no correlation between LL-37, hBD-2 and 25-hydroxyvitamin D
      levels. CONCLUSIONS Our data suggest that LL-37 and hBD-2 may play an important
      role in TB pathogenesis in children. To our knowledge, this is the first study on
      BAL LL-37 and hBD-2 concentrations in children with pulmonary TB.

PMID- 24903938
TI  - Microbiological investigation for tuberculosis among HIV-infected children in
      Soweto, South Africa.
AB  - SETTING: A paediatric human immunodeficiency virus (HIV) clinic in an academic
      hospital in Soweto, South Africa. OBJECTIVES: 1) To describe and compare the
      clinical, immunological and virological characteristics of HIV-infected children
      co-treated for tuberculosis (TB), and 2) to compare those investigated
      microbiologically with those who were not, with a description of the results of
      the microbiological TB investigation. DESIGN: Retrospective analysis of TB-HIV
      infected children aged <15 years treated for TB between 1 October 2007 and 15
      March 2009. RESULTS: Anti-tuberculosis treatment was initiated in 616/3358 (18%)
      children during the study period. Microbiological TB investigation results were
      available for 399/616 (65%), among whom culture-confirmed TB was diagnosed in 49
      (12%). Drug susceptibility testing was performed in 29/49 (59%) children: 5/29
      (17%) were isoniazid-resistant, and 3 had multidrug-resistant TB. Children aged
      >8 years and those between 3 and 8 years were more likely to have culture
      confirmed TB than those aged <3 years (aOR 9.4, 95%CI 2.26-39.08 vs. aOR 6.7,
      95%CI 1.60-27.69), as were those with CD4 count <200 cells/mm(3) compared to
      those with >500 cells/mm(3) (aOR 3.95, 95%CI 1.23-12.72). CONCLUSION: Our study
      in HIV-infected children showed a high TB case rate, a low rate of definite TB
      and a high rate of drug-resistant TB based on World Health Organization case
      definitions. Increased uptake of available TB tests and availability of new
      diagnostic tests remains a priority in high TB-HIV burden settings.

PMID- 24903940
TI  - Double-dose lopinavir-ritonavir in combination with rifampicin-based anti
      tuberculosis treatment in South Africa.
AB  - BACKGROUND: The optimal treatment for tuberculosis (TB) in human immunodeficiency
      virus (HIV) infected patients in resource-poor settings receiving lopinavir
      ritonavir (LPV/r) based second-line antiretroviral therapy (ART) has yet to be
      determined. In South Africa, clinicians are advised to use 'double-dose' LPV/r
      dosed at 800 mg/200 mg twice daily during anti-tuberculosis treatment.
      METHODOLOGY AND PRINCIPLE FINDINGS: We conducted a retrospective study of HIV
      infected patients who received >=2 months of double-dose LPV/r-based ART during
      concomitant rifampicin-containing anti-tuberculosis treatment. We used standard
      definitions for TB and HIV outcomes; virological failure was defined as a viral
      load >1000 copies/ml. During co-administration, gastro-intestinal toxicity
      occurred in 9/25 (36%) patients, a symptomatic rise in aspartate aminotransferase
      or alanine aminotransferase of any grade was noted in 3 (12%), with two Grade 3
      events, and 3 (12%) patients required treatment discontinuation. Outcomes were
      favourable, with 20/25 (80%) patients achieving TB treatment success and
      virological failure observed among 3 (12%) patients during co-administration.
      CONCLUSION: We found the use of double-dose LPV/r during simultaneous standard
      anti-tuberculosis treatment to be an effective and reasonably well tolerated
      interim strategy.

PMID- 24903939
TI  - Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group
      Protocol A5253.
AB  - OBJECTIVE: To evaluate the association between oral candidiasis and tuberculosis
      (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan
      Africa, and to investigate oral candidiasis as a potential tool for TB case
      finding. METHODS: Protocol A5253 was a cross-sectional study designed to improve
      the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence
      countries. Participants received an oral examination to detect oral candidiasis.
      We estimated the association between TB disease and oral candidiasis using
      logistic regression, and sensitivity, specificity and predictive values. RESULTS:
      Of 454 participants with TB culture results enrolled in African sites, the median
      age was 33 years, 71% were female and the median CD4 count was 257 cells/mm(3).
      Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was
      significantly higher among TB cases (35%) than among non-TB cases (16%, P <
      0.001). The odds of having TB was 2.4 times higher among those with oral
      candidiasis when controlling for CD4 count and antifungals (95%CI 1.2-4.7, P =
      0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22
      48) and the specificity 85% (95%CI 81-88). CONCLUSION: We found a strong
      association between oral candidiasis and TB disease, independent of CD4 count,
      suggesting that in resource-limited settings, oral candidiasis may provide
      clinical evidence for increased risk of TB and contribute to TB case finding.

PMID- 24903941
TI  - Delayed antiretroviral therapy despite integrated treatment for tuberculosis and
      HIV infection.
AB  - SETTING: Five primary health care clinics in Kinshasa, Democratic Republic of
      Congo. OBJECTIVE: To examine timing and predictors of delayed initiation of
      antiretroviral therapy (ART) during anti-tuberculosis treatment. DESIGN:
      Prospective observational cohort of adult patients receiving integrated treatment
      for tuberculosis (TB) and human immunodeficiency virus (HIV) who are expected to
      initiate ART at 1 month if CD4 count is <100 cells/mm(3) or if patient is World
      Health Organization (WHO) Clinical Stage 4 for reasons other than extra-pulmonary
      TB, at 2 months if CD4 count is 100-350 cells/mm(3), or at completion of anti
      tuberculosis treatment if subsequently CD4 count is <= 350 cells/mm(3) or patient
      has WHO Clinical Stage 4. RESULTS: Of 492 patients, 235 (47.8%) experienced
      delayed initiation of ART: 171 (72.8%) initiated ART late, after a median delay
      of 12 days (interquartile range [IQR] 4-27) and 64 (27.2%) never initiated ART.
      Contraindication to any antiretroviral drug (aOR 2.91, 95%CI 1.22-6.95), lower
      baseline CD4 count (aOR 1.20, 95%CI 1.08-1.33/100 cells/mm(3)), TB drug
      intolerance (aOR 1.93, 95%CI 1.23-3.02) and non-disclosure of HIV infection (aOR
      1.50, 95%CI 1.03-2.18) predicted delayed ART initiation. CONCLUSION: Despite
      fully integrated treatment, half of all patients experienced delayed ART
      initiation. Pragmatic approaches to ensure timely ART initiation in those at risk
      of delayed ART initiation are needed.

PMID- 24903943
TI  - The association of smoking with IGRA and TST results in HIV-1-infected subjects.
AB  - OBJECTIVE: To assess the association of smoking with the interferon-gamma (IFN
      gamma) release assay and tuberculin skin test (TST) results in a comparative
      study on the detection of latent tuberculous infection (LTBI) in human
      immunodeficiency virus (HIV) 1-infected individuals. METHODS: In this cross
      sectional study, 305 HIV-1-infected subjects were tested by the QuantiFERON-TB
      Gold In-Tube assay (QFT-GIT) and the TST. We evaluated the impact of smoking and
      other LTBI risk factors on QFT-GIT and TST results. RESULTS The concordance of
      both tests was 93% (kappa = 0.71, P < 0.001). The following independent risk
      factors for both QFT-GIT and TST positivity were identified: birth in a high TB
      incidence country, self-reported contact with an active TB case and elevated
      CD4(+) T-cell count (P < 0.001). While smoking was not independently associated
      with a positive QFT-GIT (OR 1.2, 95%CI 0.5-2.8) or TST result (OR 1.8, 95%CI 0.6
      5.9), there was an inverse correlation of the number of cigarettes smoked with
      IFN-gamma levels measured using QFT-GIT (rho = -0.14, P = 0.027). In addition,
      smoking was independently associated with a quantitative QFT-GIT response in
      linear regression analysis (beta = 0.129, P = 0.025). CONCLUSIONS: Although
      smoking may have a minor inhibitory effect on QFT-GIT response, QFT-GIT results
      seem not to be affected by smoking to a clinically significant extent.

PMID- 24903944
TI  - The effects of statin use on the development of tuberculosis among patients with
      diabetes mellitus.
AB  - OBJECTIVE: To evaluate whether statin use affects the development of tuberculosis
      (TB) among patients with diabetes mellitus (DM). METHODS: This is a retrospective
      cohort study of patients with newly diagnosed type 2 DM based on the South Korean
      nationwide claims database. The participants were type 2 DM patients aged 20-99
      years who were newly treated with anti-diabetic drugs between 1 January 2007 and
      31 December 2010. Patients who had statin prescriptions before a diagnosis of
      diabetes or were diagnosed with TB before diabetes were excluded. RESULTS: Of
      840,899 newly diagnosed type 2 DM patients, 281,842 (33.5%) patients were statin
      users and 559,057 (66.5%) were non-users. During the study period, 4075
      [corrected] individuals were diagnosed with TB; the estimated incidence of TB in
      our cohort was 251/100,000 patient-years (95%CI 243-258). In comparison to non-TB
      patients, statin users were less frequent among TB patients (19.2% vs. 33.6%).
      After adjustment for potential baseline confounders, statin use was not
      associated with the development of TB in DM patients (aHR 0.98; 95%CI 0.89-1.07).
      CONCLUSIONS: TB development among newly diagnosed type 2 DM was considerable, and
      statin use among these diabetics was not associated with a protective effect on
      TB incidence.

PMID- 24903945
TI  - Comparable characteristics of tuberculous and non-tuberculous mycobacterial
      cavitary lung diseases.
AB  - OBJECTIVE: To identify characteristics that differentiate lung disease due to non
      tuberculous mycobacteria (NTM) from that due to pulmonary tuberculosis (PTB) in
      acid-fast bacilli (AFB) smear-positive patients with lung cavities. METHODS: From
      2006 to 2012, 142 AFB smear- and culture-positive patients with lung cavities
      were identified at the Wonju Severance Christian Hospital, Wonju, Korea. Clinical
      and radiographic characteristics were compared between patients with NTM disease
      and PTB. RESULTS: Of 142 patients, 112 were diagnosed with PTB and 30 with NTM
      disease. Patients with NTM disease were older (62 vs. 49 years, P = 0.001), more
      likely to have had previous anti-tuberculosis treatment (18, 60.0% vs. 34, 30.6%;
      P = 0.001), more likely to have haemoptysis (9, 30.0% vs. 13, 11.9%; P = 0.022)
      and less likely to have consolidation on chest radiograph (20, 66.7% vs. 98,
      87.5%; P = 0.007) than PTB patients. Multivariate analysis showed that age >=65
      years (OR 3.37, 95%CI 1.24-9.13, P = 0.010) and previous anti-tuberculosis
      treatment (OR 3.75, 95%CI 1.46-9.65, P = 0.006) were significantly associated
      with NTM disease. CONCLUSIONS: Cavitary patients with positive AFB smears and NTM
      or PTB had considerable overlapping clinical characteristics, although patients
      aged >=65 years or with a previous history of anti-tuberculosis treatment were
      more likely to have NTM.

PMID- 24903946
TI  - Risk factors for deterioration of nodular bronchiectatic Mycobacterium avium
      complex lung disease.
AB  - SETTING The long-term natural course of Mycobacterium avium complex (MAC) disease
      with nodular bronchiectasis, the most common pulmonary non-tuberculous
      mycobacterial disease, is not well described. OBJECTIVE: To identify risk factors
      for the deterioration of nodular bronchiectatic MAC lung disease over a 5-year
      follow-up period. DESIGN: Clinical and laboratory data of 67 patients with
      nodular bronchiectatic MAC lung disease were collected. Chest computerised
      tomographic images were used to count the number of lung segments involved at
      diagnosis and measure subcutaneous fat thickness during follow-up. RESULTS: The
      34 patients who showed deterioration had significantly lower body mass index
      (BMI) (P = 0.004) and % predicted forced vital capacity (P = 0.032), higher
      numbers of lung segments involved (P < 0.001) and MAC-positive sputum cultures (P
      = 0.028), and thinner chest subcutaneous fat during follow-up (P < 0.001) than
      patients without deterioration. In particular, patients with both BMI <21.0
      kg/m(2) and more than four lung segments involved had a 240-fold increased risk
      of deterioration (P < 0.001). CONCLUSION: Patients with poor nutritional status
      and extensive lung involvement tend to experience deterioration of nodular
      bronchiectatic MAC lung disease.

PMID- 24903942
TI  - Tuberculosis in a cohort of HIV-positive patients: epidemiology, clinical
      practice and treatment outcomes.
AB  - OBJECTIVE: To describe tuberculosis (TB) incidence, risk factors, clinical
      presentation, disease management and outcomes in human immunodeficiency virus
      (HIV) infected patients from the CoRIS cohort, Spain, 2004-2010. DESIGN: Open
      multicentre cohort of antiretroviral treatment (ART) naive patients at entry.
      Incidence and risk factors were evaluated using multivariate Poisson regression.
      RESULTS: Among 6811 patients, 271 were eligible for the study and 198 for the
      estimation of the incidence rate; TB incidence ranged from 12.1 to 14.1/1000
      person-years. TB was associated with low education level (rate ratio [RR] 2.65,
      95%CI 1.73-4.07), being sub-Saharan African (RR 3.14, 95%CI 1.81-5.45),
      heterosexual (RR 2.01, 95%CI 1.22-3.29) or an injecting drug user (RR 2.11, 95%CI
      1.20-3.69), not undergoing ART (RR 3.33, 95%CI 2.22-4.76), CD4 <200 cells/mm(3)
      (RR 5.20, 95%CI 3.25-8.33) and log-viral load of 4-5 (RR 5.44, 95%CI 3.28-9.02)
      or >5 (RR 13.10, 95%CI 8.27-20.76). Overall, 87% were new cases and 13% were
      previously treated cases; 175 (65%) were bacteriologically confirmed. Drug
      susceptibility testing was performed in 146 (83%) patients: resistance to first
      line drugs was 11.1% in new and 36.4% in previously treated cases. Standard anti
      tuberculosis treatment with four or three drugs was prescribed in respectively
      55% and 36% of cases. Treatment default was 11%, and was higher among previously
      treated cases; 80% received ART during anti-tuberculosis treatment, 80% of new
      and 50% of previously treated cases were cured or completed treatment, and 18
      (6.6%) died. CONCLUSION: TB incidence in HIV-infected patients remains high.
      Interventions should include early HIV diagnosis and access to ART, enhanced
      bacteriological confirmation, wider use of four-drug regimens and reduction in
      treatment default.

PMID- 24903948
TI  - Exhaled nitric oxide and screening for occupational asthma in two at-risk
      sectors: bakery and hairdressing.
AB  - BACKGROUND: Fractional exhaled nitric oxide (FENO) levels are increasingly being
      used in the diagnosis and management of asthma. However, this indicator has
      rarely been used to detect occupational asthma. OBJECTIVE: To examine non
      invasive methods to estimate airway inflammation. METHODS: A nested case-control
      study was conducted among a retrospective cohort of young workers in the bakery,
      pastry-making and hairdressing industries. Subjects underwent a clinical
      examination during a medical visit. Blood samples were collected and FENO levels
      measured. Cases were subjects diagnosed as suffering from 'confirmed' or
      'probable' occupational asthma. RESULTS: Of the 178 workers included in the
      study, 19 were cases. In univariate analysis, FENO was associated with
      case/control status, and height and smoking status. In a multiple linear
      regression model, case/control status (P < 0.001), height (P = 0.006) and smoking
      status (P < 0.001) remained independent risk factors for variations in FENO
      levels. Good or fair sensitivity of respectively around 80% and 70% can be
      achieved using low FENO thresholds (8.5 and 10.5 ppb, respectively). FENO >8.5
      ppb and a positive clinical examination increases specificity without loss of
      sensitivity (to 80.5% and 79.0%, respectively). CONCLUSION: This study suggests
      that FENO measurements alone cannot be considered a useful screening test for
      occupational asthma. Further investigations are needed to investigate the use of
      combined FENO and questionnaire or repeated measures.

PMID- 24903947
TI  - Health care use and economic burden of patients with diagnosed chronic
      obstructive pulmonary disease in Korea.
AB  - BACKGROUND: The prevalence and economic burden of chronic obstructive pulmonary
      disease (COPD) are increasing worldwide. However, little information is available
      concerning COPD-associated health care use and costs in Korea. OBJECTIVE: To
      analyse 1) health care use, medical costs and medication use in 2009, and 2)
      changes in costs and medication use over 5 years (2006-2010). DESIGN: Using the
      database of the Korean Health Insurance Review and Assessment Service, COPD
      patients were identified by searching on both ICD-10 codes and COPD medication.
      RESULTS A total of 192,496 COPD patients were identified in 2009. Total medical
      costs per person were US$2803 +/- 3865; the average annual number of days of out
      patient care and days of hospitalisation were respectively 40 +/- 36 and 11 +/-
      33. Methylxanthine and systemic beta-agonists were the most frequently used
      drugs. However, the number of prescriptions for long-acting muscarinic antagonist
      increased rapidly. The total cost of COPD-related medications increased by 33.1%
      over 5 years. CONCLUSION: The present study provides new insight into health care
      use and the economic burden of COPD in Korea. Changing patterns of COPD-related
      medication use could help inform COPD management policies.

PMID- 24903949
TI  - Effect of smear-negative pulmonary tuberculosis on transmission.

PMID- 24903950
TI  - Update on cost-effectiveness of a 12-dose regimen for latent tuberculous
      infection at new rifapentine prices.

PMID- 24903951
TI  - In reply.

PMID- 24903952
TI  - Jacques Prignot, 2 February 1924-2 January 2014.

PMID- 24903954
TI  - Assessment of planctomycetes cell viability after pollutants exposure.
AB  - In this study, the growth of six different planctomycetes, a particular
      ubiquitous bacterial phylum, was assessed after exposure to pollutants. In
      addition and for comparative purposes, Pseudomonas putida, Escherichia coli and
      Vibrio anguillarum were tested. Each microorganism was exposed to several
      concentrations of 21 different pollutants. After exposure, bacteria were
      cultivated using the drop plate method. In general, the strains exhibited a great
      variation of sensitivity to pollutants in the order: V. anguillarum >
      planctomycetes > P. putida > E. coli. E. coli showed resistance to all pollutants
      tested, with the exception of phenol and sodium azide. Copper, Ridomil(r)
      (fungicide), hydrazine and phenol were the most toxic pollutants. Planctomycetes
      were resistant to extremely high concentrations of nitrate, nitrite and ammonium
      but they were the only bacteria sensitive to Previcur N(r) (fungicide). Sodium
      azide affected the growth on plates of E. coli, P. putida and V. anguillarum, but
      not of planctomycetes. However, this compound affected planctomycetes cell
      respiration but with less impact than in the aforementioned bacteria. Our results
      provide evidence for a diverse response of bacteria towards pollutants, which may
      influence the structuring of microbial communities in ecosystems under stress,
      and provide new insights on the ecophysiology of planctomycetes.

PMID- 24903953
TI  - Evaluating the binding efficiency of pheromone binding protein with its natural
      ligand using molecular docking and fluorescence analysis.
AB  - Chemosignals play a crucial role in social and sexual communication among inter-
      and intra-species. Chemical cues are bound with protein that is present in the
      pheromones irrespective of sex are commonly called as pheromone binding protein
      (PBP). In rats, the pheromone compounds are bound with low molecular lipocalin
      protein alpha2u-globulin (alpha2u). We reported farnesol is a natural endogenous
      ligand (compound) present in rat preputial gland as a bound volatile compound. In
      the present study, an attempt has been made through computational method to
      evaluating the binding efficiency of alpha2u with the natural ligand (farnesol)
      and standard fluorescent molecule (2-naphthol). The docking analysis revealed
      that the binding energy of farnesol and 2-naphthol was almost equal and likely to
      share some binding pocket of protein. Further, to extrapolate the results
      generated through computational approach, the alpha2u protein was purified and
      subjected to fluorescence titration and binding assay. The results showed that
      the farnesol is replaced by 2-naphthol with high hydrophobicity of TYR120 in
      binding sites of alpha2u providing an acceptable dissociation constant indicating
      the binding efficiency of alpha2u. The obtained results are in corroboration with
      the data made through computational approach. 

PMID- 24903955
TI  - Bacillus huizhouensis sp. nov., isolated from a paddy field soil.
AB  - A Gram-stain positive, facultative aerobic bacterium, designated as strain
      GSS03(T), was isolated from a paddy field soil. The cells were observed to be
      endospore forming, rod-shaped and motile with flagella. The organism was found to
      grow optimally at 35  degrees C at pH 7.0 and in the presence of 1 % NaCl. The
      strain was classified as a novel taxon within the genus Bacillus on the basis of
      phenotypic and phylogenetic analyses. The closest phylogenetic relatives were
      identified as Bacillus psychrosaccharolyticus DSM 6(T) (97.61 %), Bacillus
      muralis DSM 16288(T) (97.55 %), Bacillus asahii JCM 12112(T) (97.48 %), Bacillus
      simplex DSM 1321(T) (97.48 %) and "Bacillus frigoritolerans" DSM 8801(T) (97.38
      %). The menaquinone was identified as MK-7, the major cellular fatty acid was
      identified as anteiso-C15:0 and the major cellular polar lipids as
      phosphatidylethanolamine, phosphatidylmonomethylethanolamine,
      diphosphatidylglycerol, phosphatidylglycerol and three unknown polar lipids. The
      DNA G+C content was determined to be 40.2 mol%. The DNA-DNA relatedness with the
      closest relatives was below 48 %. Therefore, on the basis of all the results,
      strain GSS03(T) is considered to represent a novel species within the genus
      Bacillus, for which the name Bacillus huizhouensis sp. nov. is proposed. The type
      strain is GSS03(T) (=KCTC 33172(T) =CCTCC AB 2013237(T)). 

PMID- 24903956
TI  - Isolation of novel microalgae from acid mine drainage and its potential
      application for biodiesel production.
AB  - Microalgae were selected and isolated from acid mine drainage in order to find
      microalgae species which could be cultivated in low pH condition. In the present
      investigation, 30 microalgae were isolated from ten locations of acid mine
      drainage in South Korea. Four microalgae were selected based on their growth
      rate, morphology, and identified as strains of KGE1, KGE3, KGE4, and KGE7. The
      dry biomass of microalgae species ranged between 1 and 2 g L(-1) after 21 days of
      cultivation. The growth kinetics of microalgae was well described by logistic
      growth model. Among these, KGE7 has the highest biomass production (2.05 +/- 0.35
      g L(-1)), lipid productivity (0.82 +/- 0.14 g L(-1)), and C16-C18 fatty acid
      contents (97.6 %). These results suggest that Scenedesmus sp. KGE 7 can be
      utilized for biodiesel production based on its high biomass and lipid
      productivity.

PMID- 24903957
TI  - Accumulation of flavonoids and related gene expressions in different organs of
      Astragalus membranaceus Bge.
AB  - Astragalus membranaceus is one of the important medicinal plant in China and
      Korea. It is used to increase metabolism and digestion, enhance the immune
      system, and promote the healing of wounds and injuries. In the present study, we
      used quantitative real-time PCR to investigate the expression of genes related to
      the biosynthesis of flavonoids, in addition to high-performance liquid
      chromatography to assess calycosin and calycosin-7-O-beta-D-glucoside
      accumulation, in the different plant organs of A. membranaceus. The transcript
      levels of all genes (AmPAL, AmC4H, Am4CL, AmCHS, AmCHR, AmCHI, AmIFS, AmI3'H, and
      AmUCGT) involved in calycosin and calycosin-7-O-beta-D-glucoside biosynthesis
      were the highest in the flower. Calycosin content was ordered as follows: leaf
      (145.56 MUg/g dry weight [DW]) > stem (18.3 MUg/g DW) > root (1.64 MUg/g DW) >
      flower (0.09 MUg/g DW), whereas calycosin-7-O-beta-D-glucoside content was
      ordered as follows: root (4.88 MUg/g DW) > stem (3.86 MUg/g DW) > leaf (2.0 MUg/g
      DW) > flower (not detected). All genes exhibited the highest transcription levels
      in the flower, whereas calycosin and its glycoside content were the highest in
      the leaf and root, respectively. Our results indicate that the enhancement of
      calycosin-7-O-beta-D-glucoside in the roots may originate from high calycosin
      accumulation in the stem and leaf. Thus, the mechanisms regulating calycosin and
      calycosin-7-O-beta-D-glucoside content differ in the different organs of A.
      membranaceus. The results are expected to provide baseline information from which
      the mechanism of flavonoid biosynthesis in the different organs of A.
      membranaceus may be elucidated.

PMID- 24903958
TI  - Advances in detection methods of L-amino acid oxidase activity.
AB  - L-amino acid oxidase (LAAO) is widely distributed in many different organisms and
      found to play important biological roles, thus attracting a great deal of
      attention for characterization of its activity. Diverse detection methods with
      their own properties have been established. This review advanced different LAAO
      activity assays based on substrate consumption, cofactor amount, and product
      accumulation. The description of benefits and drawbacks of each method is
      expected to help researchers find appropriate detection method of LAAO activity
      for their own purpose.

PMID- 24903959
TI  - Functional nucleic-acid-based sensors for environmental monitoring.
AB  - Efforts to replace conventional chromatographic methods for environmental
      monitoring with cheaper and easy to use biosensors for precise detection and
      estimation of hazardous environmental toxicants, water or air borne pathogens as
      well as various other chemicals and biologics are gaining momentum. Out of the
      various types of biosensors classified according to their bio-recognition
      principle, nucleic-acid-based sensors have shown high potential in terms of cost,
      sensitivity, and specificity. The discovery of catalytic activities of RNA
      (ribozymes) and DNA (DNAzymes) which could be triggered by divalent metallic ions
      paved the way for their extensive use in detection of heavy metal contaminants in
      environment. This was followed with the invention of small oligonucleotide
      sequences called aptamers which can fold into specific 3D conformation under
      suitable conditions after binding to target molecules. Due to their high
      affinity, specificity, reusability, stability, and non-immunogenicity to vast
      array of targets like small and macromolecules from organic, inorganic, and
      biological origin, they can often be exploited as sensors in industrial waste
      management, pollution control, and environmental toxicology. Further, rational
      combination of the catalytic activity of DNAzymes and RNAzymes along with the
      sequence-specific binding ability of aptamers have given rise to the most
      advanced form of functional nucleic-acid-based sensors called aptazymes.
      Functional nucleic-acid-based sensors (FNASs) can be conjugated with fluorescent
      molecules, metallic nanoparticles, or quantum dots to aid in rapid detection of a
      variety of target molecules by target-induced structure switch (TISS) mode.
      Although intensive research is being carried out for further improvements of FNAs
      as sensors, challenges remain in integrating such bio-recognition element with
      advanced transduction platform to enable its use as a networked analytical system
      for tailor made analysis of environmental monitoring. 

PMID- 24903960
TI  - Construction of spherical liposome on solid transducers for electrochemical DNA
      sensing and transfection.
AB  - Cationic 1,2-dioleoyl trimethyl ammonium propane (DOTAP) and neutral 1,2-dioleoyl
      sn-glycero-3-phosphoethanolamine (DOPE) are anchored on cysteamine (cyst),
      mercaptopropionic acid (MPA) monolayer (thiol monolayers) modified on an
      individual gold transducer. DOTAP and DOPE are mixed with gold nanoparticle
      (AuNP) to form spherical liposome-AuNP. The electrochemical behaviors of the
      surface attached DOTAP-AuNP and DOPE-AuNP in presence of [Fe(CN)6](3-/4-) depend
      on the method of layer formation. Transmission electron microscopy (TEM), Fourier
      transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and
      ultraviolet (UV)-visible spectroscopic techniques are used to characterize the
      liposome-AuNP nanocomposite. The studies indicate stability of spherical liposome
      AuNP on the gold transducer. Label-free DNA hybridization detection on these
      surfaces reveals different detection limits. Confocal laser scanning microscopy
      (CLSM) is used to confirm the cell transfection. 

PMID- 24903962
TI  - Mutation breeding of lycopene-producing strain Blakeslea trispora by a novel
      atmospheric and room temperature plasma (ARTP).
AB  - To improve the fermentation efficiency of lycopene, a plasma jet, driven by an
      active helium atom supplied with atmospheric and room temperature plasma (ARTP)
      biological breeding system, was used as a new method to generate mutations in
      Blakeslea trispora (-). After several rounds of screening, a mutant A5 with high
      concentration of lycopene and dry biomass was isolated, which showed a maximum
      lycopene concentration (26.4 +/- 0.2 mg/g dry biomass) which was 55 % higher than
      the parent strain (16.9 +/- 0.3 mg/g dry biomass) in the production of lycopene.
      Compared with parent strain, B. trispora A5 required less dissolved oxygen (10 %
      less than that of parent strain) to reach maximum concentration in a 5-L stirred
      tank reactor batch fermentation.

PMID- 24903961
TI  - Nanomaterial-based biosensors for food toxin detection.
AB  - There is an increased interest toward the development of bioelectronic devices
      for food toxin (mycotoxins) detection. Mycotoxins are highly toxic secondary
      metabolites produced by fungi like Fusarium, Aspergillus, and Penicillium that
      are frequently found in crops or during storage of food including cereals, nuts,
      fruits, etc. The contamination of food by mycotoxins has become a matter of
      increasing concern. High levels of mycotoxins in the diet can cause adverse,
      acute, and chronic effects on human health and a variety of animal species. Side
      effects may particularly affect the liver, kidney, nervous system, endocrine
      system, and immune system. Among 300 mycotoxins known till date, there are a few
      that are considered to play an important part in food safety, and for these, a
      range of analytical methods have been developed. Some of the important mycotoxins
      include aflatoxins, ochratoxins, fumonisins, citreoviridin, patulin, citrinin,
      and zearalenon. The conventional methods of analysis of mycotoxins normally
      require sophisticated instrumentation, e.g., liquid chromatography with
      fluorescence or mass detectors, combined with extraction procedures for sample
      preparation. Hence, new analysis tools are necessary to attain more sensitive,
      specific, rapid, and reliable information about the desired toxin. For the last
      about two decades, the research and development of simpler and faster analytical
      procedures based on affinity biosensors has aroused much interest due to their
      simplicity and sensitivity. The nanomaterials have recently had a great impact on
      the development of biosensors. The functionalized nanomaterials are used as
      catalytic tools, immobilization platforms, or as optical or electroactive labels
      to improve the biosensing performance to obtain higher sensitivity, stability,
      and selectivity. Nanomaterials, such as carbon nanomaterials (carbon nanotubes
      and graphene), metal nanoparticles, nanowires, nanocomposites, and nanostructured
      metal oxide nanoparticles are playing an increasing role in the design of sensing
      and biosensing systems for mycotoxin determination. Furthermore, these
      nanobiosystems are also bringing advantages in terms of the design of novel food
      toxin detection strategies. We will focus on some of the recent results related
      to fabrication of nanomaterial-based biosensors for food toxin detection obtained
      in our laboratories. 

PMID- 24903963
TI  - Immobilization of horseradish peroxidase enzyme on nanoporous titanium dioxide
      electrodes and its structural and electrochemical characterizations.
AB  - Hierarchically ordered, honeycomb-like nanoporous TiO2 electrodes are prepared by
      a simple electrochemical anodization process using ammonium fluoride dissolved in
      ethylene glycol as an electrolytic medium. Formation of hexagonally arranged
      nanopores along with the tubular structure and anatase crystalline phase of TiO2
      is confirmed by field emission scanning electron microscope (FESEM) and X-ray
      diffraction (XRD) studies. Further, these nanoporous TiO2 electrodes are employed
      as a substrate for enzyme (horseradish peroxidase, HRP) immobilization in an
      attempt to enhance the electron transport across the semiconductor electrode
      electrolyte interface. Two different strategies, namely, physical entrapment and
      covalent linking, are used for anchoring the enzyme. Various parameters such as
      conductivity, stability, enzyme loading, enzymatic activity, sensitivity, linear
      range, etc., are investigated by using electrochemical techniques. Structural and
      morphological analyses of enzyme-modified electrodes are carried out using
      spectroscopic (UV - vis) and microscopic (AFM) methods. In the case of physical
      entrapment, a simple drop casting method of HRP solution on the nanoporous TiO2
      electrodes is used in contrast to chemical linking method where a monolayer of 3
      aminopropyltrimethoxy silane (APTMS) is formed initially on TiO2 followed by HRP
      immobilization using an amide coupling reaction. Interestingly, both of these
      methods result in anchoring of HRP enzyme, but the amount of enzyme loading and
      the stability are found to be higher in the covalent linking method. Cyclic
      voltammetric studies reveal the formation of a well-defined reversible peak for
      HRP enzyme. Dependence of peak current with the scan rate suggests that HRP
      enzyme is immobilized and stable and that the overall electron transfer process
      is predominantly controlled by a diffusion process. Enzymatic activity of HRP is
      investigated by monitoring the reduction process of hydrogen peroxide by
      incremental addition using cyclic voltammetry and amperometry techniques, from
      which several kinetic parameters are determined. 

PMID- 24903965
TI  - Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone
      turnover markers and bone mineral density in women with breast cancer.
AB  - PURPOSE: While their negative impact on bone health is well established, the
      effects of aromatase inhibition (AI) on Wnt inhibitors and osteoprotegerin (OPG)
      are unknown. The aim of the study was to investigate the effects of AI on serum
      levels of sclerostin, DKK-1 and OPG, as well as their associations with PINP and
      CTX as markers of bone turnover and bone mineral density (BMD) assessed by DXA.
      METHODS: We conducted a prospective longitudinal analysis of 70 postmenopausal
      women with hormone receptor-positive early breast cancer (BC) treated with
      anastrozole. All measurements were performed at baseline, 12 and 24 months of
      treatment. We measured the association of the investigated variables with
      circulating bone turnover markers, as well as with the BMD. RESULTS: After 24
      months of AI therapy, sclerostin and OPG concentrations increased from 29.5
      pmol/l (SD = 15.1) and 6.8 pmol/l (SD = 2.2) at baseline to 43.2 pmol/l (SD =
      20.6) (p < 0.001) and 7.4 pmol/l (SD = 2.2) (p = 0.028), respectively. DKK-1
      levels decreased from 34.3 pmol/l (SD = 13.5) at baseline to 29.7 pmol/l (SD =
      12.3) at the 24-month visit (p = 0.005). Sclerostin levels significantly
      correlated with PTH, OPG and BMD of the lumbar spine, while DKK-1 correlated with
      the BMD of the femoral neck and of the total hip. CONCLUSIONS: The observed
      increase in sclerostin levels indicates a central role of osteocytes in bone
      turnover in women with BC.

PMID- 24903964
TI  - Advanced non-small cell lung cancer management in patients progressing after
      first-line treatment: results of the cross-sectional phase of the Italian LIFE
      observational study.
AB  - PURPOSE: LIFE (non-small cell Lung cancer management In patients progressing
      after First-linE of treatment in the metastatic setting) is a multicentre Italian
      observational study, including a cross-sectional and a longitudinal phase, with
      the aim of describing the therapeutic approach in clinical practice for advanced
      non-small cell lung cancer (NSCLC) patients, progressing after first-line
      treatment. METHODS: In this paper, the cross-sectional phase is outlined, with
      the primary endpoint of describing the proportion of patients receiving second
      line treatment among those progressed during or after first-line treatment
      according to clinical practice. RESULTS: From July 2011 to January 2012, 603
      patients were enrolled and 541 (90 %) were evaluable. A total of 464 (86 %)
      patients received a second-line therapy outside clinical trials. Chemotherapy and
      targeted therapies were administered to 65 and 34 % of patients, respectively (1
      % both). No tissue collection was required within the observational trial, and
      biomarkers analysis was performed at diagnosis or later in 314 patients (58 %).
      In details, activating epidermal growth factor receptor mutations were detected
      in 21 % of 311 evaluable patients, Kirsten rat sarcoma 2 viral oncogene homolog
      mutation in 22 % of the 77 evaluable patients and anaplastic lymphoma kinase
      translocations analysis was performed in 74 patients and resulted positive in 23
      % of cases. These high proportions were probably due to enriched patient
      population tested. CONCLUSIONS: These results showed a pattern of care for NSCLC
      second-line therapy which reflects international guidelines recommendations and
      current expected clinical practice. Interestingly, biomarkers analyses were
      performed in a higher percentage than expected.

PMID- 24903967
TI  - Presence of voltage-gated potassium channel complex antibody in a case of genetic
      prion disease.
AB  - Voltage-gated potassium channel (VGKC) complex antibody-mediated encephalitis is
      a recently recognised entity which has been reported to mimic the clinical
      presentation of Creutzfeldt-Jakob disease (CJD). Testing for the presence of this
      neuronal surface autoantibody in patients presenting with subacute encephalopathy
      is therefore crucial as it may both revoke the bleak diagnosis of prion disease
      and allow institution of potentially life-saving immunotherapy. Tempering this
      optimistic view is the rare instance when a positive VGKC complex antibody titre
      occurs in a definite case of prion disease. We present a pathologically and
      genetically confirmed case of CJD with elevated serum VGKC complex antibody
      titres. This case highlights the importance of interpreting the result of a
      positive VGKC complex antibody with caution and in the context of the overall
      clinical manifestation. 

PMID- 24903966
TI  - The association between sex-related interleukin-6 gene polymorphisms and the risk
      for cerebral palsy.
AB  - BACKGROUND: The relationship between genetic factors and the development of
      cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the
      genes encoding proinflammatory cytokines have been shown to be associated with
      susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL
      6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain
      injury, but conflicting results have been reported regarding the association
      between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this
      study was to analyze IL-6 gene polymorphisms and protein expression and to
      explore the role of IL-6 in the Chinese CP population. METHODS: A total of 753
      healthy controls and 713 CP patients were studied to detect the presence of five
      SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6
      locus. Of these, 77 healthy controls and 87 CP patients were selected for
      measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to
      analyze the genotyping data. For all comparisons; multiple testing on each
      individual SNP was corrected by the SNPSpD program. RESULTS: There were no
      differences in allele or genotype frequencies between the overall CP patients and
      controls among the five genetic polymorphisms. However, subgroup analysis found
      significant sex-related differences in allele and genotype frequencies.
      Differences were found between spastic CP and controls in males for rs2069837;
      between CP with periventricular leukomalacia and controls in males for rs1800796
      and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL
      6 levels were higher in CP patients than in the controls, and this difference was
      more robust in full-term male spastic CP patients. Furthermore, the genotype has
      an effect on IL-6 synthesis. CONCLUSIONS: The influence of IL-6 gene
      polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex
      and gestational age.

PMID- 24903968
TI  - Direct access to the middle meningeal artery for embolization of complex dural
      arteriovenous fistula: a hybrid treatment approach.
AB  - Endovascular embolization has become increasingly favored over microsurgical
      resection for treatment of complex dural arteriovenous fistulas (DAVFs). However,
      endovascular treatment can be restricted by tortuous transarterial access and a
      transvenous approach is not always feasible. We present a Borden III DAVF treated
      by direct access to the middle meningeal artery (MMA) and Onyx embolization
      performed in a hybrid operating room-angiography suite. A middle-aged patient
      with pulsatile headaches was found to have left transverse sinus occlusion and
      DAVF with retrograde cortical venous drainage fed by multiple external carotid
      artery (ECA) feeders. Endovascular attempts via conventional transvenous and
      transarterial routes were unsuccessful, and the major MMA feeder was accessed
      directly after temporal craniotomy was performed under neuronavigation. Onyx
      embolization was performed; complete occlusion of the fistula was achieved. Three
      month follow-up angiography showed no residual filling; the patient remains
      complication-free. A combined surgical-endovascular technique in a hybrid
      operating room-angiography suite can be an effective treatment for DAVFs
      complicated by inaccessible arterial and transvenous approaches. 

PMID- 24903969
TI  - Unexplained extensive calcification of the venae cavae extending into the right
      atrium causing partial obstruction of the tricuspid valve.

PMID- 24903970
TI  - Resection of pancreatic head neoplasm in a patient with previous coronary bypass
      grafting using right gastroepiploic artery.

PMID- 24903971
TI  - HLA-DRB1 and susceptibility to kidney allograft rejection in Southern Iranian
      patients.
AB  - Kidney transplantation is the best treatment option for the patients with end
      stage renal disease. Viral infections and genetic factors such as HLA-II antigens
      may affect the kidney transplant outcome. The compatibility of HLA-DRB1 molecules
      in the survival of kidney transplant is important. Also, the correlation between
      these molecules and viral infections is significant. The current study
      investigates the allele frequency of HLA-DRB1 in 41 recipient kidney transplant
      and 203 normal healthy controls by polymerase chain reaction using sequence
      specific primers. Moreover the relation between HLA-DRB1 allelic groups and
      hepatitis B, hepatitis C and cytomegalovirus viral infections was also studied.
      However statistical analysis of the allele frequencies didn't show any
      significant association between HLA-DRB1 allelic group distributions or sharing
      and susceptibility to acute kidney transplant rejection (P > 0.05). Comparing the
      allele frequencies between HLA-DRB1*14 and DRB1*04 allelic showed a significant
      difference in controls and patients (P = 0.03 and P = 0.05 respectively). The
      results of the present study also showed a significant association between
      possession of HLA-DRB1*07 allele in kidney transplant recipients and hepatitis C
      virus infection (P = 0.009). In conclusion however the results of the present
      study did not showed relation between HLA-DRB1 allele's frequencies or sharing
      and kidney transplantation outcome, the results indicated that HLA-DRB1 alleles
      may susceptible individuals to renal disease or play a role in susceptibility to
      viral infection in kidney transplant patients.

PMID- 24903972
TI  - Genetic predisposition to calcific aortic stenosis and mitral annular
      calcification.
AB  - Valvular calcification precedes the development of valvular stenosis and may
      represent an important early phenotype for valvular heart disease. It is known
      that development of valvular calcification is likely to occur among members of a
      family. However, the knowledge about the role of genomic predictive markers in
      valvular calcification is still elusive. Aims of this review are to assess the
      impact of gene polymorphisms on risk and severity of aortic stenosis and mitral
      annular calcification. According to the results of the investigations carried
      out, all polymorphisms may be divided into the three groups conferring the level
      of evidence of their association with valvular stenosis. It is possible to
      conclude that apoB (XbaI, rs1042031, and rs6725189), ACE (rs4340), IL10
      (rs1800896 and rs1800872), and LPA (rs10455872) gene polymorphisms may be
      associated with valvular calcific stenosis with a relatively high level of
      evidence. A number of other polymorphisms, such as PvuII polymorphism within the
      ORalpha gene, rs1042636 polymorphism within the CaSR gene, rs3024491, rs3021094,
      rs1554286, and rs3024498 polymorphisms within the IL10 gene, rs662 polymorphism
      within the PON1 gene, rs2276288 polymorphism within the MYO7A gene, rs5194
      polymorphism within the AGTR1 gene, rs2071307 polymorphism within the ELN gene,
      rs17659543 and rs13415097 polymorphisms within the IL1F9 gene may correlate with
      a risk of calcific valve stenosis with moderate level of evidence. Finally,
      rs1544410 polymorphism within the VDR gene, E2 and E4 alleles within the apoE
      gene, rs6254 polymorphism within the PTH gene, and rs1800871 polymorphism within
      the IL10 gene may be associated with aortic stenosis with low level of evidence.

PMID- 24903973
TI  - Cilostazol suppresses beta-amyloid production by activating a disintegrin and
      metalloproteinase 10 via the upregulation of SIRT1-coupled retinoic acid receptor
      beta.
AB  - The accumulation of plaques of beta-amyloid (Abeta) peptides, a hallmark of
      Alzheimer's disease, results from the sequential cleavage of amyloid precursor
      protein (APP) by activation of beta- and gamma-secretases. However, the
      production of Abeta can be avoided by alternate cleavage of APP by alpha-and
      gamma-secretases. We hypothesized that cilostazol attenuates Abeta production by
      increasing a disintegrin and metalloproteinase 10 (ADAM10)/alpha-secretase
      activity via SIRT1-coupled retinoic acid receptor-beta (RARbeta) activation in
      N2a cells expressing human APP Swedish mutation (N2aSwe). To evoke endogenous
      Abeta overproduction, the culture medium was switched from medium containing 10%
      fetal bovine serum (FBS) to medium containing 1% FBS, and cells were cultured for
      3~24 hr. After depletion of FBS in media, N2aSwe cells showed increased
      accumulations of full-length APP (FL-APP) and Abeta in a time-dependent manner (3
      24 hr) in association with decreased ADAM10 protein expression. When pretreated
      with cilostazol (10-30 MUM), FL-APP and Abeta levels were significantly reduced,
      and ADAM10 and alpha-secretase activities were restored. Furthermore, the effect
      of cilostazol on ADAM10 expression was antagonized by pretreating Rp-cAMPS and
      sirtinol and by SIRT1-gene silencing. In the N2aSwe cells overexpressing the
      SIRT1 gene, ADAM10, and sAPPalpha levels were significantly elevated. In
      addition, like all-trans retinoic acid, cilostazol enhanced the protein
      expressions of RARbeta and ADAM10, and the cilostazol-stimulated ADAM10 elevation
      was significantly attenuated by LE135 (a RARbeta inhibitor), sirtinol, and
      RARbeta-gene silencing. In conclusion, cilostazol suppresses the accumulations of
      FL-APP and Abeta by activating ADAM10 via the upregulation of SIRT1-coupled
      RARbeta.

PMID- 24903974
TI  - The neuropsychology of male adults with high-functioning autism or asperger
      syndrome.
AB  - Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms,
      but cognitive abilities may also be useful in characterizing individuals with
      ASD. One hundred seventy-eight high-functioning male adults, half with ASD and
      half without, completed tasks assessing IQ, a broad range of cognitive skills,
      and autistic and comorbid symptomatology. The aims of the study were, first, to
      determine whether significant differences existed between cases and controls on
      cognitive tasks, and whether cognitive profiles, derived using a multivariate
      classification method with data from multiple cognitive tasks, could distinguish
      between the two groups. Second, to establish whether cognitive skill level was
      correlated with degree of autistic symptom severity, and third, whether cognitive
      skill level was correlated with degree of comorbid psychopathology. Fourth,
      cognitive characteristics of individuals with Asperger Syndrome (AS) and high
      functioning autism (HFA) were compared. After controlling for IQ, ASD and control
      groups scored significantly differently on tasks of social cognition, motor
      performance, and executive function (P's < 0.05). To investigate cognitive
      profiles, 12 variables were entered into a support vector machine (SVM), which
      achieved good classification accuracy (81%) at a level significantly better than
      chance (P < 0.0001). After correcting for multiple correlations, there were no
      significant associations between cognitive performance and severity of either
      autistic or comorbid symptomatology. There were no significant differences
      between AS and HFA groups on the cognitive tasks. Cognitive classification models
      could be a useful aid to the diagnostic process when used in conjunction with
      other data sources-including clinical history.

PMID- 24903976
TI  - Neuroprotective effect of exercise in rat hippocampal slices submitted to in
      vitro ischemia is promoted by decrease of glutamate release and pro-apoptotic
      markers.
AB  - The role of physical exercise as a neuroprotective agent against ischemic injury
      has been extensively discussed. Nevertheless, the mechanisms underlying the
      effects of physical exercise on cerebral ischemia remain poorly understood. Here,
      we investigate the hypothesis that physical exercise increases ischemic tolerance
      by decreasing the induction of cellular apoptosis and glutamate release. Rats (n
      = 50) were submitted to a swimming exercise protocol for 8 weeks. Hippocampal
      slices were then submitted to oxygen and glucose deprivation. Cellular viability,
      pro-apoptotic markers (Caspase 8, Caspase 9, Caspase 3, and apoptosis-inducing
      factor), and glutamate release were analyzed. The percentage of cell death, the
      amount of glutamate release, and the expression of the apoptotic markers were all
      decreased in the exercise group when compared to the sedentary group after oxygen
      and glucose deprivation. Our results suggest that physical exercise protects
      hippocampal slices from the effects of oxygen and glucose deprivation, probably
      by a mechanism involving both the decrease of glutamatergic excitotoxicity and
      apoptosis induction.

PMID- 24903977
TI  - Evaluating the balance regulating matrix remodeling.

PMID- 24903975
TI  - Mesenchymal stem cell therapy and acute graft-versus-host disease: a review.
AB  - Mesenchymal stem cells (MSCs) are being widely studied as potential cell therapy
      agents due to their immunomodulatory properties, which have been established by
      in vitro studies and in several clinical trials. Within this context, mesenchymal
      stem cell therapy appears to hold substantial promise, particularly in the
      treatment of conditions involving autoimmune and inflammatory components.
      Nevertheless, many research findings are still contradictory, mostly due to
      difficulties in characterization of the effects of MSCs in vivo. The purpose of
      this review is to report the mechanisms underlying mesenchymal stem cell therapy
      for acute graft-versus-host disease, particularly with respect to
      immunomodulation, migration, and homing, as well as report clinical applications
      described in the literature. 

PMID- 24903978
TI  - Atrial tachyarrhythmias induced by the combined effects of beta1/2-adrenergic
      autoantibodies and thyroid hormone in the rabbit.
AB  - Activating autoantibodies (AAb) to beta-adrenergic receptors (betaAR) are
      associated with atrial fibrillation in patients with Graves' disease. In the
      present study, we examined the interaction of thyroid hormone with beta1/2AR-AAb
      in inducing atrial tachyarrhythmias in the rabbit. Immunization of rabbits with a
      beta1AR or beta2AR second extracellular loop peptide produced high titers of
      beta1AR-AAb or beta2AR-AAb. Thyroid hormone in combination with beta1AR-AAb or
      beta2AR-AAb induced a significant number of sustained sinus tachycardia and
      atrial tachycardia, respectively. Both combinations resulted in significantly
      increased inductions of sustained arrhythmias compared to AAb alone. Thyroid
      hormone alone induced sustained sinus and junctional tachycardia. Sera from
      immunized rabbits specifically bound to and activated beta1AR or beta2AR in
      transfected cells in vitro. This study demonstrates thyroid hormone qualitatively
      accentuates the specific arrhythmogenic action of these AAb and quantitatively
      enhances their rate. Our data support a dual role of AAb and thyroid hormone in
      Graves'-associated tachyarrhythmias. 

PMID- 24903979
TI  - A consensus map for Ug99 stem rust resistance loci in wheat.
AB  - KEY MESSAGE: This consensus map of stem rust genes, QTLs, and molecular markers
      will facilitate the identification of new resistance genes and provide a resource
      of in formation for development of new markers for breeding wheat varieties
      resistant to Ug99. The global effort to identify new sources of resistance to
      wheat stem rust, caused by Puccinia graminis f. sp. tritici race group Ug99 has
      resulted in numerous studies reporting both qualitative genes and quantitative
      trait loci. The purpose of our study was to assemble all available information on
      loci associated with stem rust resistance from 21 recent studies on Triticum
      aestivum L. (bread wheat) and Triticum turgidum subsp. durum desf. (durum wheat).
      The software LPmerge was used to construct a stem rust resistance loci consensus
      wheat map with 1,433 markers incorporating Single Nucleotide Polymorphism,
      Diversity Arrays Technology, Genotyping-by-Sequencing as well as Simple Sequence
      Repeat marker information. Most of the markers associated with stem rust
      resistance have been identified in more than one population. Several loci
      identified in these populations map to the same regions with known Sr genes
      including Sr2, SrND643, Sr25 and Sr57 (Lr34/Yr18/Pm38), while other significant
      markers were located in chromosome regions where no Sr genes have been previously
      reported. This consensus map provides a comprehensive source of information on
      141 stem rust resistance loci conferring resistance to stem rust Ug99 as well as
      linked markers for use in marker-assisted selection.

PMID- 24903980
TI  - CO, CO2 and H2 adsorption on ZnO, CeO2, and ZnO/CeO2 surfaces: DFT simulations.
AB  - The adsorption of the molecules CO, CO2, and H2 on several ceria and zinc oxide
      surfaces was studied by means of periodical DFT calculations and compared with
      infrared frequency data. The stable CeO2(111), CeO2(331), and ZnO(0001) perfect
      faces were the first substrates considered. Afterwards, the same surfaces with
      oxygen vacancies and a ZnO monolayer grown on Ceria(111) were also studied in
      order to compare the behaviors and reactivities of the molecules at those
      surfaces. The ceria surfaces were substantially more reactive than the ZnO
      surface towards the CO2 molecule. The highest adsorption energy for this molecule
      was obtained on the CeO2(111) surface with oxygen vacancies. The molecules CO and
      H2 both presented low or very low reactivities on all of the surfaces studied,
      although some reactivity was observed for the adsorption of CO onto the surfaces
      with oxygen vacancies, whereas H2 exhibited reactivity towards the CeO2(111)
      surface with oxygen vacancies. This work was performed to provide a firm
      foundation for novel process development in methanol synthesis from carbon
      oxides, steam reforming of methanol for hydrogen production, and/or the water-gas
      shift reaction. 

PMID- 24903981
TI  - Miktoarm star polymer based multifunctional traceable nanocarriers for efficient
      delivery of poorly water soluble pharmacological agents.
AB  - A versatile methodology to develop an inherently fluorescent and thus traceable
      multifunctional nanodelivery platform based on miktoarm polymers is reported.
      Miktoarm stars containing covalently linked tetraiodofluorescein dye,
      polyethylene glycol, and polycaprolactone self-assemble into micelles, and
      integrate multiple functions including fluorescent tags for imaging, a
      hydrophobic core for drug incorporation, and a hydrophilic corona for micelle
      stabilization. Curcumin, a pleiotropic but very poorly water-soluble drug, is
      loaded into these micelles with an efficiency of 25-60 wt%. It leads to a 25 000
      fold increase in its aqueous solubility, and a sustained release over a period of
      7 d. These micelles are rapidly internalized into murine J774A.1 macrophages, and
      accumulated into discrete cellular compartments, whereas the free and physically
      encapsulated dye is diffused in the cytoplasm. Curcumin-loaded micelles reduce
      lipopolysaccharide-induced nitric oxide release. The studies establish miktoarm
      star based nanocarriers as highly efficient in tracking their fate and expanding
      the scope of pharmacological agents with limited utility in experimental
      medicine. 

PMID- 24903982
TI  - Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic
      Stenosis study.
AB  - BACKGROUND AND PURPOSE: There are limited data on risk stratification of stroke
      in aortic stenosis. This study examined predictors of stroke in aortic stenosis,
      the prognostic implications of stroke, and how aortic valve replacement (AVR)
      with or without concomitant coronary artery bypass grafting influenced the
      predicted outcomes. METHODS: Patients with mild-to-moderate aortic stenosis
      enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.
      Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were
      exclusion criteria. Ischemic stroke was the primary end point, and poststroke
      survival a secondary outcome. Cox models treating AVR as a time-varying covariate
      were adjusted for atrial fibrillation and congestive heart failure, hypertension,
      age>=75 years, diabetes mellitus, stroke/transient ischemic attack, vascular
      disease, age 65-74 years and female sex (CHA2DS2-VASc) scores. RESULTS: One
      thousand five hundred nine patients were followed for 4.3+/-0.8 years (6529
      patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre-
      and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation
      (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1-6.6), CHA2DS2-VASc
      score (HR 1.4 per unit; 95% CI, 1.1-1.8), diastolic blood pressure (HR, 1.4 per
      10 mm Hg; 95% CI, 1.1-1.8), and AVR with concomitant coronary artery bypass
      grafting (HR, 3.2; 95% CI, 1.4-7.2, all P<=0.026) were independently associated
      with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7-14.0;
      P<0.001). CONCLUSIONS: In patients with aortic stenosis not prescribed oral
      anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass
      grafting, and CHA2DS2-VASc score were the major predictors of stroke. Incident
      stroke was strongly associated with mortality. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

PMID- 24903983
TI  - Second European Stroke Science Workshop.

PMID- 24903984
TI  - Cognitive deterioration in bilateral asymptomatic severe carotid stenosis.
AB  - BACKGROUND AND PURPOSE: This study aimed to monitor cognitive performance during
      a 3-year period in subjects with bilateral asymptomatic severe internal carotid
      artery stenosis and to explore the role of cerebral hemodynamics and
      atherosclerotic disease in the development of cognitive dysfunction. METHODS: One
      hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid
      artery stenosis were included and prospectively evaluated for a 3-year period. At
      entry, demographics, vascular risk profile, and pharmacological treatments were
      defined. Cognitive status was evaluated using the Mini-Mental State Examination
      at baseline and at follow-up. Cerebral hemodynamics was assessed by transcranial
      Doppler-based breath-holding index test. As a measure of the extent of systemic
      atherosclerotic disease, common carotid artery intima-media thickness was
      measured. A cutoff for pathological values was set at 0.69 for breath-holding
      index and 1.0 mm for intima-media thickness. RESULTS: The risk of decreasing in
      Mini-Mental State Examination score increased progressively from patients with
      bilaterally normal to those with unilaterally abnormal breath-holding index,
      reaching the highest probability in patients with bilaterally abnormal breath
      holding index (P<0.0001). Pathological values of intima-media thickness did not
      influence the risk of Mini-Mental State Examination score change. CONCLUSIONS:
      Our findings suggest that patients with asymptomatic bilateral severe internal
      carotid artery stenosis may be at risk of developing cognitive impairment. The
      evaluation of the hemodynamic status, besides providing insights about the
      possible mechanism behind the cognitive dysfunction present in carotid
      atherosclerotic disease, may be of help for the individuation of subjects
      deserving earlier and more aggressive treatments.

PMID- 24903985
TI  - Point-of-care cluster randomized trial in stroke secondary prevention using
      electronic health records.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate whether the remote
      introduction of electronic decision support tools into family practices improves
      risk factor control after first stroke. This study also aimed to develop methods
      to implement cluster randomized trials in stroke using electronic health records.
      METHODS: Family practices were recruited from the UK Clinical Practice Research
      Datalink and allocated to intervention and control trial arms by minimization.
      Remotely installed, electronic decision support tools promoted intensified
      secondary prevention for 12 months with last measure of systolic blood pressure
      as the primary outcome. Outcome data from electronic health records were analyzed
      using marginal models. RESULTS: There were 106 Clinical Practice Research
      Datalink family practices allocated (intervention, 53; control, 53), with 11 391
      (control, 5516; intervention, 5875) participants with acute stroke ever
      diagnosed. Participants at trial practices had similar characteristics as 47,887
      patients with stroke at nontrial practices. During the intervention period, blood
      pressure values were recorded in the electronic health records for 90% and
      cholesterol values for 84% of participants. After intervention, the latest mean
      systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and
      131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference
      was -0.56 mm Hg (95% confidence interval, -1.38 to 0.26; P=0.183). The financial
      cost of the trial was approximately US $22 per participant, or US $2400 per
      family practice allocated. CONCLUSIONS: Large pragmatic intervention studies may
      be implemented at low cost by using electronic health records. The intervention
      used in this trial was not found to be effective, and further research is needed
      to develop more effective intervention strategies. CLINICAL TRIAL REGISTRATION
      URL: http://www.controlled-trials.com. Current Controlled Trials identifier:
      ISRCTN35701810.

PMID- 24903986
TI  - Acute cerebrovascular disease occurring after hospital discharge for labor and
      delivery.
AB  - BACKGROUND AND PURPOSE: The risk of stroke and other postpartum cerebrovascular
      disease (CVD) occurring after hospital discharge for labor and delivery is
      uncertain. METHODS: We performed a retrospective cohort study using
      administrative databases to identify all pregnant women who were hospitalized for
      labor and delivery at nonfederal, acute care hospitals in California from 2005 to
      2011 and who were discharged without an International Classification of Diseases,
      Ninth Revision, Clinical Modification diagnosis of CVD. The primary outcome was
      an acute CVD composite defined as any ischemic stroke, intracranial hemorrhage,
      cerebral venous sinus thrombosis, pituitary apoplexy, carotid/vertebral artery
      dissection, hypertensive encephalopathy, or other acute CVD occurring after
      hospital discharge and before 6 weeks after labor and delivery. Descriptive
      statistics were used to estimate the incidence of postdischarge CVD. Multivariate
      logistic regression was used to evaluate the association between selected
      baseline factors and postdischarge CVD. RESULTS: The rate of any postdischarge
      acute CVD was 14.8 per 100 000 patients (95% confidence interval [CI], 13.2
      16.5). Risk factors for any acute CVD were eclampsia (odds ratio [OR], 10.1; 95%
      CI, 3.09-32.8), chronic kidney disease (OR, 5.4; 95% CI, 2.5-11.8), black race
      (OR, 2.5; 95% CI, 1.9-3.3), preeclampsia (OR, 2.1; 95% CI, 1.6-2.8), pregnancy
      related hematologic disorders (OR, 1.8; 95% CI, 1.3-2.5), and age (OR, 1.5 per
      decade; 95% CI, 1.3-1.8). CONCLUSIONS: The incidence of postpartum acute CVD
      after hospital discharge for labor and delivery is similar to rates reported for
      all postpartum events in previous publications, suggesting that a substantial
      proportion of postpartum CVD occurs after discharge.

PMID- 24903988
TI  - Streptomycin inhibits electrophysiological changes induced by stretching of
      chronically infarcted rat hearts.
AB  - OBJECTIVE: To investigate stretch-induced electrophysiological changes in
      chronically infarcted hearts and the effect of streptomycin (SM) on these changes
      in vivo. METHODS: Sixty Wistar rats were divided randomly into four groups: a
      control group (n=15), an SM group (n=15), a myocardial infarction (MI) group
      (n=15), and an MI+SM group (n=15). Chronic MI was obtained by ligating the left
      anterior descending branch (LAD) of rat hearts for eight weeks. The in vivo
      blockade of stretch-activated ion channels (SACs) was achieved by intramuscular
      injection of SM (180 mg/(kg?d)) for seven days after operation. The hearts were
      stretched for 5 s by occlusion of the aortic arch. Suction electrodes were placed
      on the anterior wall of left ventricle to record the monophasic action potential
      (MAP). The effect of stretching was examined by assessing the 90% monophasic
      action potential duration (MAPD90), premature ventricular beats (PVBs), and
      ventricular tachycardia (VT). RESULTS: The MAPD90 decreased during stretching in
      both the control (from (50.27+/-5.61) ms to (46.27+/-4.51) ms, P<0.05) and MI
      groups (from (65.47+/-6.38) ms to (57.47+/-5.76 ms), P<0.01). SM inhibited the
      decrease in MAPD90 during inflation ((46.27+/-4.51) ms vs. (49.53+/-3.52) ms,
      P<0.05 in normal hearts; (57.47+/-5.76) ms vs. (61.87+/-5.33) ms, P<0.05 in MI
      hearts). The occurrence of PVBs and VT in the MI group increased compared with
      that in the control group (PVB: 7.93+/-1.66 vs. 1.80+/-0.86, P<0.01; VT: 7 vs. 1,
      P<0.05). SM decreased the occurrence of PVBs in both normal and MI hearts (0.93+/
      0.59 vs. 1.80+/-0.86 in normal hearts, P<0.05; 5.40+/-1.18 vs. 7.93+/-1.66 in MI
      hearts, P<0.01). CONCLUSIONS: Stretch-induced MAPD90 changes and arrhythmias were
      observed in chronically infarcted myocardium. The use of SM in vivo decreased the
      incidence of PVBs but not of VT. This suggests that SACs may be involved in
      mechanoelectric feedback (MEF), but that there might be other mechanisms involved
      in causing VT in chronic MI.

PMID- 24903987
TI  - Is right ventricular mid-septal pacing superior to apical pacing in patients with
      high degree atrio-ventricular block and moderately depressed left ventricular
      function?
AB  - OBJECTIVE: We are aimed to investigate whether right ventricular mid-septal
      pacing (RVMSP) is superior to conventional right ventricular apical pacing (RVAP)
      in improving clinical functional capacity and left ventricular ejection fraction
      (LVEF) for patients with high-degree atrio-ventricular block and moderately
      depressed left ventricle (LV) function. METHODS: Ninety-two patients with high
      degree atrio-ventricular block and moderately reduced LVEF (ranging from 35% to
      50%) were randomly allocated to RVMSP (n=45) and RVAP (n=47). New York Heart
      Association (NYHA) functional class, echocardiographic LVEF, and distance during
      a 6-min walk test (6MWT) were determined at 18 months after pacemaker
      implantation. Serum levels of N-terminal pro-brain natriuretic peptide (NT
      proBNP) were measured using an enzyme-linked immunosorbent assay (ELISA) kit.
      RESULTS: Compared with baseline, NYHA functional class remained unchanged at 18
      months, distance during 6MWT (485 m vs. 517 m) and LVEF (36.7% vs. 41.8%) were
      increased, but BNP levels were reduced (2352 pg/ml vs. 710 pg/ml) in the RVMSP
      group compared with those in the RVAP group, especially in patients with LVEF 35%
      40% (for all comparisons, P<0.05). However, clinical function capacity and LV
      function measurements were not significantly changed in patients with RVAP,
      despite the pacing measurements being similar in both groups, such as R-wave
      amplitude and capture threshold. CONCLUSIONS: RVMSP provides a better clinical
      utility, compared with RVAP, in patients with high-degree atrioventricular block
      and moderately depressed LV function whose LVEF levels ranged from 35% to 40%.

PMID- 24903989
TI  - Anterolateral minithoracotomy versus median sternotomy for mitral valve disease:
      a meta-analysis.
AB  - OBJECTIVE: Mitral valve disease tends to be treated with anterolateral
      minithoracotomy (ALMT) rather than median sternotomy (MS), as ALMT uses
      progressively smaller incisions to promote better cosmetic outcomes. This meta
      analysis quantifies the effects of ALMT on surgical parameters and post-operative
      outcomes compared with MS. METHODS: One randomized controlled study and four case
      control studies, published in English from January 1996 to January 2013, were
      identified and evaluated. RESULTS: ALMT showed a significantly longer
      cardiopulmonary bypass time (P=0.001) and aortic cross-clamp time (P=0.05)
      compared with MS. However, the benefits of ALMT were evident as demonstrated by a
      shorter length of hospital stay (P<0.00001). According to operative
      complications, the onset of new arrhythmias following ALMT decreased
      significantly as compared with MS (P=0.05); however, the incidence of peri
      operative mortality (P=0.62), re-operation for bleeding (P=0.37), neurologic
      events (P=0.77), myocardial infarction (P=0.84), gastrointestinal complications
      (P=0.89), and renal insufficiency (P=0.67) were similar to these of MS. Long-term
      follow-up data were also examined, and revealed equivalent survival and freedom
      from mitral valve events. CONCLUSIONS: Current clinical data suggest that ALMT is
      a safe and effective alternative to the conventional approach and is associated
      with better short-term outcomes and a trend towards longer survival.

PMID- 24903990
TI  - Green tea polyphenol, epigallocatechin-3-gallate, possesses the antiviral
      activity necessary to fight against the hepatitis B virus replication in vitro.
AB  - Although several antiviral drugs and vaccines are available for use against
      hepatitis B virus (HBV), hepatitis caused by HBV remains a major public health
      problem worldwide, which has not yet been resolved, and new anti-HBV drugs are in
      great demand. The present study was performed to investigate the anti-HBV
      activity of epigallocatechin-3-gallate (EGCG), a natural-origin compound, in
      HepG2 2.2.15 cells. The antiviral activity of EGCG was examined by detecting the
      levels of HBsAg and HBeAg in the supernatant and extracellular HBV DNA. EGCG
      effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells
      in a dose- and time-dependent manner, and it showed stronger effects at the level
      of 0.11-0.44 MUmol/ml (50-200 MUg/ml) than lamivudine (3TC) at 0.87 MUmol/ml (200
      MUg/ml). EGCG also suppressed the amount of extracellular HBV DNA. The data
      indicated that EGCG possessed anti-HBV activity and suggested the potential of
      EGCG as an effective anti-HBV agent with low toxicity. 

PMID- 24903991
TI  - Ferulic acid prevents liver injury and increases the anti-tumor effect of
      diosbulbin B in vivo.
AB  - The present study is designed to investigate the protection by ferulic acid
      against the hepatotoxicity induced by diosbulbin B and its possible mechanism,
      and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor
      activity. The results show that ferulic acid decreases diosbulbin B-increased
      serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid
      also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B
      treated mice. Histological evaluation of the liver demonstrates hydropic
      degeneration in diosbulbin B-treated mice, while ferulic acid reverses this
      injury. Moreover, the activities of copper- and zinc-containing superoxide
      dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin
      B-treated mice, while ferulic acid reverses these decreases. Further results
      demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated
      mouse liver are significantly decreased, while ferulic acid prevents this
      decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor
      growth inhibition compared with diosbulbin B alone. Taken together, the present
      study shows that ferulic acid prevents diosbulbin B-induced liver injury via
      ameliorating diosbulbin B-induced liver oxidative stress injury and augments
      diosbulbin B-induced anti-tumor activity. 

PMID- 24903992
TI  - Antioxidant activity and protective effect of Clitoria ternatea flower extract on
      testicular damage induced by ketoconazole in rats.
AB  - BACKGROUND: Ketoconazole (KET), an antifungal drug, has adverse effects on the
      male reproductive system. Pre-treatments with antioxidant plant against
      testicular damage induced by KET are required. The flowers of Clitoria ternatea
      (CT) are proven to have hepatoprotective potential. However, the protective
      effect on KET-induced testicular damage has not been reported. OBJECTIVE: To
      investigate the protective effect of CT flower extracts with antioxidant activity
      on male reproductive parameters including sperm concentration, serum testosterone
      level, histopathology of the testis, and testicular tyrosine phosphorylation
      levels in rats induced with KET. METHODS: The antioxidant activity of CT flower
      extracts was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric
      reducing antioxidant power (FRAP) assays. Male rats were treated with CT flower
      extracts (10, 50, or 100 mg/kg BW) or distilled water via a gastric tube for 28 d
      (preventive period: Days 1-21) and induced by KET (100 mg/kg BW) via
      intraperitoneal injection for 7 d (induction period: Days 22-28). After the
      experiment, all animals were examined for the weights of the testis, epididymis
      plus vas deferens and seminal vesicle, serum testosterone levels, sperm
      concentration, histological structures and diameter of testis, and testicular
      tyrosine phosphorylation levels by immunoblotting. RESULTS: The CT flower
      extracts had capabilities for DPPH scavenging and high reducing power. At 100
      mg/kg BW, the extract had no toxic effects on the male reproductive system.
      Significantly, in CT+KET groups, CT flower extracts (50 and 100 mg/kg BW)
      alleviated the reduction of reproductive organ weight parameters, testosterone
      levels, and sperm concentration. In addition, CT flower extracts gave protection
      from testicular damage in KET-induced rats. Moreover, in the CT100+KET group, CT
      flower extracts significantly enhanced the expression of a testicular 50-kDa
      tyrosine phosphorylated protein compared with that of other groups. CONCLUSIONS:
      C. ternatea flower extracts possessing antioxidant activity are not harmful to
      the male reproductive system and can protect against testicular damage in KET
      induced rats.

PMID- 24903994
TI  - Proteins induced by telomere dysfunction are associated with human IgA
      nephropathy.
AB  - Aging is one of the contributing risk factors for kidney diseases. Accumulating
      evidence prompts the view that telomere length in kidney tissue cells is an
      indicator for organismal aging. Previously identified aging markers (cathelin
      related antimicrobial peptide (CRAMP), stathmin, elongation factor-1alpha (EF
      1alpha), and chitinase) were associated not only with telomere driven aging in
      mice but also with human aging and chronic diseases. This study focuses on the
      relationship between these biomarkers and IgA nephropathy (IgAN) progression in
      the Chinese population. For 260 individuals, the four markers are determined in
      blind datasets using direct enzyme-linked immunosorbent assay (ELISA) and
      immunofluorescence staining. The expression levels of CRAMP and chitinase
      increased in blood plasma, urine, and kidney tissues during human IgAN
      progression. And for the other nephropathy, such as systemic lupus erythematosus
      (SLE), diabetic nephropathy (DN), and focal segmental glomerulosclerosis (FSGS),
      there is no protein upregulation with telomere shortening. Moreover, a
      combination of CRAMP and chitinase can distinguish patients with IgAN from
      healthy individuals with 88.2%/92.5% (plasma) and 74.3%/84.2% (urine)
      sensitivity/specificity. These data provide the experimental evidence that
      telomere shortening and related inflammatory proteins are associated with human
      IgAN, and it could be a new direction for the disease progression study. 

PMID- 24903993
TI  - Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal
      injury in rats with severe acute pancreatitis.
AB  - BACKGROUND AND OBJECTIVE: It has been shown that macrophages play an important
      role in the development of severe acute pancreatitis (SAP), and eventually lead
      to multiple organ failure (MOF). Clodronate-liposome selectively depleted
      macrophages. This study was to investigate the role of renal macrophage
      infiltration in acute renal injury in rats with SAP and to evaluate the potential
      of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI)
      for diagnosis. METHODS: Superparamagnetic Fe3O4 nanoparticles were prepared by
      chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were
      prepared by the thin film method. SAP models were prepared by injection of sodium
      taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were
      randomly divided into a control group, SAP plus SPIO-liposome (P) group, and SAP
      plus SPIO-clodronate-containing liposome (T) group. Kidney injury was evaluated
      by T2-weighted MRI scan. The levels of serum amylase (SAM), blood urea nitrogen
      (BUN), and serum creatinine (SCr) were measured by an automated enzymatic method.
      Serum tumor necrosis factor-alpha (TNF-alpha) was measured by enzyme-linked
      immunosorbent assay (ELISA). Pathological changes in the pancreas and kidney were
      observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was
      detected with terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) staining. In addition, the macrophage markers (CD68) of the renal tissue
      were detected with immunohistochemistry. RESULTS: The pathological changes in the
      pancreas and kidneys of rats in the T group were milder than those in the P
      group. The MRI signal intensity of the kidneys in the P and T groups was
      significantly lower than that in the control group. There were significant
      changes in the two experimental groups (P<0.01). The levels of SAM, Bun, SCr, and
      TNF-alpha in rats in the P group were higher than those in the control group
      (P<0.01) and in the T group (P<0.01). The apoptosis of the kidney in the T group
      was higher than that in the P group at 2 and 6 h (P<0.01). CONCLUSIONS:
      Clodronate-containing liposomes protected against renal injury in SAP rats, and
      SPIO can be used as a tracer for MRI examination to detect renal injury in SAP
      rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the
      migration of macrophages after renal injury in rats with SAP.

PMID- 24903995
TI  - A preliminary evaluation of VEGF-A, VEGFR1 and VEGFR2 in patients with well
      controlled type 2 diabetes mellitus.
AB  - OBJECTIVE: Decompensated chronic hyperglycemia often leads to late microvascular
      complications such as retinopathy, diabetic foot syndrome, and diabetic kidney
      disease. The aim of this study was to determine the concentration of vascular
      endothelial growth factor A (VEGF-A) and its receptors in patients with well
      controlled diabetes. METHODS: The study was conducted on 31 patients with well
      controlled type 2 diabetes without micro- or macroangiopathy. Thirty healthy
      volunteers were enrolled in a control group. Serum concentrations of VEGF-A, VEGF
      receptors 1 and 2 (VEGFR1 and VEGFR2), fasting glucose, and lipid profiles were
      measured, and the plasma concentration of glycated hemoglobin (HbA1c) was
      determined. RESULTS: No significant differences were observed between the
      concentration of VEGF-A, VEGFR1 or VEGFR2 in the subject group and that in the
      control group. Positive correlations were noted between the levels of VEGF-A,
      VEGFR2, and triglyceride, and there was a negative correlation between the levels
      of VEGFR2 and high-density lipoprotein (HDL)-cholesterol in the study group.
      CONCLUSIONS: The concentrations of VEGF-A and its receptors 1 and 2 in patients
      with well-controlled diabetes are comparable to those of healthy individuals,
      which may indicate that appropriate control of glucose levels delays the
      occurrence of vascular complications. A negative correlation between VEGFR2 and
      HDL-cholesterol levels, and positive correlations between VEGF-A, VEGFR2, and
      triglyceride levels, suggest that lipid abnormalities occurring in diabetes may
      be involved in the modulation of angiogenesis.

PMID- 24903996
TI  - HER-2 overexpression and survival in colorectal cancer: a meta-analysis.
AB  - OBJECTIVE: Numerous studies examining the relationship between human epidermal
      growth factor receptor 2 (HER-2) overexpression and survival in patients with
      colorectal cancer (CRC) have yielded controversial results. We therefore
      performed a meta-analysis more precisely to estimate its prognostic value.
      METHODS: Published studies investigating the effect of HER-2 overexpression on
      CRC survival were identified; the hazard ratios (HRs) and their corresponding 95%
      confidence intervals (95% CIs) were pooled in terms of disease-specific or
      overall survival. RESULTS: Eleven studies were included in the meta-analysis. The
      pooled data showed that HER-2 overexpression was negatively related to CRC
      survival (HR=1.10, 95% CI: 0.77-1.44). Subgroup analyses regarding test method
      and study quality also demonstrated little association between HER-2
      overexpression and CRC survival (HR=0.89, 95% CI: 0.50-1.29; HR=0.90, 95% CI:
      0.43-1.37, respectively). CONCLUSIONS: Regardless of several limitations, our
      study suggested that HER-2 overexpression probably had little impact on CRC
      survival.

PMID- 24903997
TI  - A cross-sectional study of irritable bowel syndrome in nurses in China:
      prevalence and associated psychological and lifestyle factors.
AB  - The prevalence of irritable bowel syndrome (IBS) and associated factors,
      especially psychological and lifestyle factors, in nurses in China have not been
      investigated previously. The aims of this study were to assess the prevalence of
      IBS in nurses, to evaluate whether factors, such as psychological disorders, are
      associated with IBS, and to determine whether psychological disorders can
      influence the severity of symptoms of IBS and quality of life (QOL). A cross
      sectional study was conducted for Chinese nurses from November 2012 to February
      2013. Participants were asked to complete questionnaires. The prevalence of IBS
      was 17.4%. The revised symptom checklist 90 (SCL-90-R) scores were significantly
      higher for nurses with IBS than for those without IBS (P<0.001), and no
      difference in scores between IBS subtypes was found (F=1.893, P=0.142). The
      scores of QOL for nurses with and without IBS were 77.18+/-21.93 and 88.44+/
      11.89 (P<0.001), respectively. Psychological disorders did not show statistically
      significant correlations with severity of symptoms of IBS or QOL. Alcohol
      consumption, low level of exercise, and psychological disorders were risk factors
      for IBS. In summary, nurses in China show a high prevalence of IBS. Psychological
      disorders and some related lifestyle factors are probably responsible for the
      development of IBS in nurses. 

PMID- 24903998
TI  - Hypocalcemia: a reversible cause of T wave alternans and heart failure.

PMID- 24903999
TI  - Expression of Transthyretin during bovine myogenic satellite cell
      differentiation.
AB  - Adult myogenesis responsible for the maintenance and repair of muscle tissue is
      mainly under the control of myogenic regulatory factors (MRFs) and a few other
      genes. Transthyretin gene (TTR), codes for a carrier protein for thyroxin (T4)
      and retinol binding protein bound with retinol in blood plasma, plays a critical
      role during the early stages of myogenesis. Herein, we investigated the
      relationship of TTR with other muscle-specific genes and report their expression
      in muscle satellite cells (MSCs), and increased messenger RNA (mRNA) and protein
      expression of TTR during MSCs differentiation. Silencing of TTR resulted in
      decreased myotube formation and decreased expression of myosin light chain
      (MYL2), myosin heavy chain 3 (MYH3), matrix gla protein (MGP), and voltage
      dependent L type calcium channel (Cav1.1) genes. Increased mRNA expression
      observed in TTR and other myogenic genes with the addition of T4 decreased
      significantly following TTR knockdown, indicating the critical role of TTR in T4
      transportation. Similarly, decreased expression of MGP and Cav1.1 following TTR
      knockdown signifies the dual role of TTR in controlling muscle myogenesis via
      regulation of T4 and calcium channel. Our computational and experimental
      evidences indicate that TTR has a relationship with MRFs and may act on calcium
      channel and related genes. 

PMID- 24904001
TI  - Tumor formation and antitumor immunity; the overlooked significance of histamine.
AB  - HA is a biogenic amine, widely distributed throughout the body. Given the
      observations that HA, the decarboxylated amino acid histidine, can be induced and
      made available in an unstored, diffusible form in tissues undergoing rapid growth
      (such as tumors and regenerating tissues), it could have a role in antitumor
      response beyond the well-studied inflammatory and allergic responses. 

PMID- 24904003
TI  - Abstracts from the 16th International Symposium on Pediatric Neuro-Oncology in
      conjunction with the 8th St. Jude-VIVA Forum, June 28 - July 2, 2014, Singapore.

PMID- 24904000
TI  - Respiratory viral infection, epithelial cytokines, and innate lymphoid cells in
      asthma exacerbations.
AB  - Exacerbations of asthma are most commonly triggered by viral infections, which
      amplify allergic inflammation. Cytokines released by virus-infected AECs may be
      important in driving this response. This review focuses on accumulating evidence
      in support of a role for epithelial cytokines, including IL-33, IL-25, and TSLP,
      as well as their targets, type 2 innate lymphoid cells (ILC2s), in the
      pathogenesis of virus-induced asthma exacerbations. Production and release of
      these cytokines lead to recruitment and activation of ILC2s, which secrete
      mediators, including IL-5 and IL-13, which augment allergic inflammation.
      However, little information is currently available about the induction of these
      responses by the respiratory viruses that are strongly associated with
      exacerbations of asthma, such as rhinoviruses. Further human studies, as well as
      improved animal experimental models, are needed to investigate appropriately the
      pathogenetic mechanisms in virus-induced exacerbations of asthma, including the
      role of ILCs. 

PMID- 24904002
TI  - Increased prevalence of psoriasis in patients with coronary artery disease:
      results from a case-control study.
AB  - BACKGROUND: The incidence of myocardial events has been reported to be increased
      in patients with psoriasis. OBJECTIVES: To investigate whether psoriasis is an
      independent risk factor for coronary artery disease (CAD). METHODS: We compared
      the prevalence of psoriasis between case patients with a diagnosis of CAD based
      on coronary angiography findings and control patients with no CAD referred to the
      emergency surgery department for an acute noncardiovascular condition. Case and
      control patients were examined for the presence of psoriasis by two
      dermatologists. The prevalence of psoriasis was compared among patients with CAD
      according to CAD severity. Five-hundred cases and 500 age- and sex-matched
      controls were included. RESULTS: Using matched univariate analysis, the
      prevalence of psoriasis was about twofold higher in CAD case patients than in
      control patients [8.0% vs. 3.4%, odds ratio (OR) 2.64; 95% confidence interval
      (CI) 1.42-4.88]. Using unconditional multivariate analysis, the association of
      psoriasis with CAD appeared to be borderline significant (OR 1.84; 95% CI 0.99
      3.40). Psoriasis in patients with CAD was significantly associated with three
      vessel involvement relative to one-or two-vessel involvement (13.1% vs. 6.1%; OR
      3.07; 95% CI 1.50-6.25). CONCLUSIONS: The prevalence of psoriasis is twofold
      higher in patients with CAD than in control patients without CAD. It is
      associated with a more severe coronary artery involvement.

PMID- 24904004
TI  - Sonographic anatomy of the pubic symphysis in healthy nulliparous women.
AB  - Pregnancy-related symphyseal pain is a condition commonly encountered by
      clinicians but its pathogenesis is poorly understood. The pubic symphysis is
      readily visualized with ultrasound, yet the normal sonographic anatomy of the
      joint has not been accurately documented. This study aimed to describe the
      anatomy of the pubic symphysis in healthy, nulliparous women using ultrasound. An
      experienced and inexperienced sonographer scanned the joint in 30 female
      volunteers (mean age 26 years). Interobserver and intraobserver reliability of
      ultrasound measurements were examined and the accuracy of these measurements was
      validated by ultrasound and dissection of six female cadaver pelves (mean age 75
      years). In healthy young women, pubic symphysis morphology varied, and six
      categories of anterosuperior joint shape were defined. Mean values of several
      anatomic parameters were obtained in supine and standing positions: joint width
      (widest 10.1 mm, narrowest 2.6 mm); superior pubic ligament (SPL) length and
      depth (41.4 and 3.4 mm, respectively); and pubic crest length (left 24.4 mm,
      right 24.4 mm). Statistically significant relationships between SPL width and
      depth and anthropometric variables (body mass index, pelvic width, and body fat
      percentage) were established. Larger ultrasonographic measurements, such as wide
      joint width and SPL length, could be measured more reliably than smaller
      measurements, such as narrow joint width and SPL depth, in both healthy
      volunteers and cadavers. Findings from this study provide normative reference
      data for examination of the pubic symphysis in pregnant women and may therefore
      be relevant to understand pregnancy-related symphyseal pain.

PMID- 24904005
TI  - ?Relvar Ellipta for COPD.
AB  - ?Relvar Ellipta 92 MUg/22 MUg (GSK) is a dry powder inhaler that contains a
      corticosteroid (fluticasone furoate) and a long-acting beta2 agonist (vilanterol
      trifenatate).1 Neither ingredient is currently marketed as a single-ingredient
      inhalation product, although fluticasone furoate is available as a nasal spray
      for the treatment of allergic rhinitis. Relvar Ellipta 92 MUg/22 MUg is licensed
      for once-daily use as maintenance therapy for chronic obstructive pulmonary
      disease (COPD) and asthma. In this article we consider the evidence for its use
      in the management of patients with COPD. An article in a future issue will review
      its use in the management of patients with asthma.

PMID- 24904006
TI  - Copper-free click reactions with polar bicyclononyne derivatives for modulation
      of cellular imaging.
AB  - The ability of cells to incorporate azidosugars metabolically is a useful tool
      for extracellular glycan labelling. The exposed azide moiety can covalently react
      with alkynes, such as bicyclo[6.1.0]nonyne (BCN), by strain-promoted alkyne-azide
      cycloaddition (SPAAC). However, the use of SPAAC can be hampered by low
      specificity of the cycloalkyne. In this article we describe the synthesis of more
      polar BCN derivatives and their properties for selective cellular glycan
      labelling. The new polar derivatives [amino-BCN, glutarylamino-BCN and
      bis(hydroxymethyl)-BCN] display reaction rates similar to those of BCN and are
      less cell-permeable. The labelling specificity in HEK293 cells is greater than
      that of BCN, as determined by confocal microscopy and flow cytometry.
      Interestingly, amino-BCN appears to be highly specific for the Golgi apparatus.
      In addition, the polar BCN derivatives label the N-glycan of the membrane calcium
      channel TRPV5 in HEK293 cells with significantly enhanced signal-to-noise ratios.

PMID- 24904007
TI  - Laparotomy closure using an elastic suture: a promising approach.
AB  - BACKGROUND: Midline laparotomy wound failure like burst abdomen remains one of
      the major complications after abdominal surgery. The use of sutures with a closer
      resemblance to abdominal wall physiology, like elastic threads, could decrease
      the risk of these complications occurring. Thus, we evaluated the possibility of
      using a new elastic thread composed of thermoplastic polyurethane (TPU) as a
      suture for the closure of midline laparotomies compared to conventionally used
      polypropylene (PP) in a rabbit model. METHODS: The elastic TPU thread was
      processed and tensile tests were performed. Twenty female chinchilla rabbits
      underwent midline laparotomy. They were randomized to a TPU and a PP group
      depending on the suture used for fascia closure. After 7 or 21 days, the
      abdominal walls were assessed macroscopically for wound healing complications and
      were explanted for histopathological investigation. RESULTS: Tensile tests showed
      a mean elastic elongation of 55.5% and a sufficient material strength of the TPU
      thread. In animal experiments, there was no difference between the groups at 7
      days; however, the TPU suture showed significantly less CD68 positive cells (p <
      0.001) and a higher collagen I/III ratio (p = 0.011) than PP did after 21 days.
      The amount of apoptotic cells was significantly elevated in the TPU group (p =
      0.007) after 21 days. No differences were found concerning granuloma size and
      number of Ki67-positive cells. CONCLUSIONS: The newly developed TPU thread shows
      promising tensile characteristics. Midline laparotomy closure is feasible and
      safe in a rabbit model. Immunohistochemistry indicates similar biocompatibility
      and wound healing after implantation compared to PP after 21 days. To confirm
      these findings and to proof long-term capability further studies need to be
      conducted.

PMID- 24904008
TI  - Lessons from diversity of directed evolution experiments by an analysis of 3,000
      mutations.
AB  - Diversity generation by random mutagenesis is often the first key step in
      directed evolution experiments and screening of 1,000-2,000 clones is in most
      directed evolution campaigns sufficient to identify improved variants. For
      experimentalists important questions such as how many positions are mutated in
      the targeted gene and what amino acid substitutions can be expected after
      screening of 1,000-2,000 clones are surprisingly not answered by a statistical
      analysis of mutant libraries. Therefore three random mutagenesis experiments
      (epPCR with a low- and a high-mutation frequency and a transversion-enriched
      sequence saturation mutagenesis method named SeSaM-Tv P/P) were performed on the
      lipase BSLA and in total 3,000 mutations were analyzed to determine the diversity
      in random mutagenesis libraries employed in directed evolution experiments. The
      active fraction of the population ranged from 15% (epPCR-high), to 52% (SeSaM-Tv
      P/P), and 55% (epPCR-low) which correlates well with the average number of amino
      acid substitutions per protein (4.1, 1.6 and 1.1). In the epPCR libraries
      transitions were the predominant mutations (>72%), and >82% of all mutations
      occurred at A- or T-nts. Consecutive nucleotide (nt) mutations were obtained only
      with a low fraction (2.8%) under highly error-prone conditions. SeSaM-Tv P/P was
      enriched in transversions (43%; >1.7-fold more than epPCR libraries), and
      consecutive nt mutations (30.5%; 11-fold more than epPCR-high). A high fraction
      of wild-type BSLA protein (33%) was found in the epPCR-low mutant library
      compared to 2% in epPCR-high and 13% in SeSaM-Tv P/P. An average of 1.8-1.9 amino
      acid substitutions per residue was obtained with epPCR-low and -high compared to
      2.1 via SeSaM-Tv P/P. The chemical composition of the amino acid substitutions
      differed, however, significantly from the two epPCR methods to SeSaM-Tv P/P.

PMID- 24904009
TI  - A comparison of women with child-adolescent versus adult onset binge eating:
      results from the National Women's Study.
AB  - OBJECTIVE: Studies of age of first binge have been conducted in clinical samples
      of patients with bulimia nervosa (BN) and binge eating disorder (BED), but few
      studies have examined age of first binge using nationally representative samples.
      METHOD: We examined age of first binge and its clinical correlates using data
      generated from the National Women's Study (n = 3,006). Participants who endorsed
      ever binge eating (n = 707) were divided into two groups: (1) child-adolescent
      onset (CO)--age of first binge <18 years, and (2) adult onset (AO)--age of first
      binge >=18 years. We hypothesized that CO binge eating would be associated with
      greater (1) likelihood of developing BN/BED, (2) severity of BN/BED, (3) history
      of trauma and PTSD, and (4) history of psychiatric comorbidity, such as major
      depression and substance use. RESULTS: Of those who ever endorsed binge eating,
      212 reported CO (30%) and 495 (70%) reported AO. Although AO binge eating was
      more common, CO binge eating was associated with higher rates of lifetime BN,
      greater severity of bulimic symptoms, earlier age of first dieting; earlier age
      at highest weight, greater likelihood of ED treatment, and higher rates of
      molestation, physical assault, any direct victimization, lifetime PTSD, and
      substance abuse. CONCLUSIONS: AO binge eating is more than twice as common as CO
      binge eating in women, but CO binge eating is associated with higher rates of
      lifetime BN, greater severity of BN, and higher rates of victimization, PTSD, and
      substance abuse.

PMID- 24904011
TI  - Mycobacterial phylogenomics: an enhanced method for gene turnover analysis
      reveals uneven levels of gene gain and loss among species and gene families.
AB  - Species of the genus Mycobacterium differ in several features, from geographic
      ranges, and degree of pathogenicity, to ecological and host preferences. The
      recent availability of several fully sequenced genomes for a number of these
      species enabled the comparative study of the genetic determinants of this wide
      lifestyle diversity. Here, we applied two complementary phylogenetic-based
      approaches using information from 19 Mycobacterium genomes to obtain a more
      comprehensive view of the evolution of this genus. First, we inferred the
      phylogenetic relationships using two new approaches, one based on a Mycobacterium
      specific amino acid substitution matrix and the other on a gene content
      dissimilarity matrix. Then, we utilized our recently developed gain-and-death
      stochastic models to study gene turnover dynamics in this genus in a maximum
      likelihood framework. We uncovered a scenario that differs markedly from
      traditional 16S rRNA data and improves upon recent phylogenomic approaches. We
      also found that the rates of gene gain and death are high and unevenly
      distributed both across species and across gene families, further supporting the
      utility of the new models of rate heterogeneity applied in a phylogenetic
      context. Finally, the functional annotation of the most expanded or contracted
      gene families revealed that the transposable elements and the fatty acid
      metabolism-related gene families are the most important drivers of gene content
      evolution in Mycobacterium. 

PMID- 24904010
TI  - Attenuated virulence and genomic reductive evolution in the entomopathogenic
      bacterial symbiont species, Xenorhabdus poinarii.
AB  - Bacteria of the genus Xenorhabdus are symbionts of soil entomopathogenic
      nematodes of the genus Steinernema. This symbiotic association constitutes an
      insecticidal complex active against a wide range of insect pests. Unlike other
      Xenorhabdus species, Xenorhabdus poinarii is avirulent when injected into insects
      in the absence of its nematode host. We sequenced the genome of the X. poinarii
      strain G6 and the closely related but virulent X. doucetiae strain FRM16. G6 had
      a smaller genome (500-700 kb smaller) than virulent Xenorhabdus strains and
      lacked genes encoding potential virulence factors (hemolysins, type 5 secretion
      systems, enzymes involved in the synthesis of secondary metabolites, and toxin
      antitoxin systems). The genomes of all the X. poinarii strains analyzed here had
      a similar small size. We did not observe the accumulation of pseudogenes,
      insertion sequences or decrease in coding density usually seen as a sign of
      genomic erosion driven by genetic drift in host-adapted bacteria. Instead, genome
      reduction of X. poinarii seems to have been mediated by the excision of genomic
      blocks from the flexible genome, as reported for the genomes of attenuated free
      pathogenic bacteria and some facultative mutualistic bacteria growing exclusively
      within hosts. This evolutionary pathway probably reflects the adaptation of X.
      poinarii to specific host. 

PMID- 24904012
TI  - Genes and junk in plant mitochondria-repair mechanisms and selection.
AB  - Plant mitochondrial genomes have very low mutation rates. In contrast, they also
      rearrange and expand frequently. This is easily understood if DNA repair in genes
      is accomplished by accurate mechanisms, whereas less accurate mechanisms
      including nonhomologous end joining or break-induced replication are used in
      nongenes. An important question is how different mechanisms of repair predominate
      in coding and noncoding DNA, although one possible mechanism is transcription
      coupled repair (TCR). This work tests the predictions of TCR and finds no support
      for it. Examination of the mutation spectra and rates in genes and junk reveals
      what DNA repair mechanisms are available to plant mitochondria, and what
      selective forces act on the repair products. A model is proposed that mismatches
      and other DNA damages are repaired by converting them into double-strand breaks
      (DSBs). These can then be repaired by any of the DSB repair mechanisms, both
      accurate and inaccurate. Natural selection will eliminate coding regions repaired
      by inaccurate mechanisms, accounting for the low mutation rates in genes, whereas
      mutations, rearrangements, and expansions generated by inaccurate repair in
      noncoding regions will persist. Support for this model includes the structure of
      the mitochondrial mutS homolog in plants, which is fused to a double-strand
      endonuclease. The model proposes that plant mitochondria do not distinguish a
      damaged or mismatched DNA strand from the undamaged strand, they simply cut both
      strands and perform homology-based DSB repair. This plant-specific strategy for
      protecting future generations from mitochondrial DNA damage has the side effect
      of genome expansions and rearrangements. 

PMID- 24904013
TI  - Glycoprotein hormones and their receptors emerged at the origin of metazoans.
AB  - The cystine knot growth factor (CKGF) superfamily includes important secreted
      developmental regulators, including the families of transforming growth factor
      beta, nerve growth factor, platelet-derived growth factor, and the glycoprotein
      hormones (GPHs). The evolutionary origin of the GPHs and the related invertebrate
      bursicon hormone, and their characteristic receptors, contributes to an
      understanding of the endocrine system in metazoans. Using a sensitive search
      method with hidden Markov models, we identified homologs of the hormones and
      receptors, along with the closely related bone morphogenetic protein (BMP)
      antagonists in basal metazoans. In sponges and a comb jelly, cystine knot
      hormones (CKHs) with mixed features of GPHs, bursicon, and BMP antagonists were
      identified using primary sequence and phylogenetic analysis. Also, we identified
      potential receptors for these CKHs, leucine-rich repeat-containing G protein
      coupled receptors (LGRs), in the same species. Cnidarians, such as the sea
      anemone, coral, and hydra, diverged later in metazoan evolution and appear to
      have duplicated and differentiated CKH-like peptides resulting in bursicon/GPH
      like peptides and several BMP antagonists: Gremlin (Grem), sclerostin domain
      containing (SOSD), neuroblastoma suppressor of tumorigenicity 1 (NBL1), and
      Norrie disease protein. An expanded cnidarian LGR group also evolved, including
      receptors for GPH and bursicon. With the appearance of bilaterians, a separate
      GPH (thyrostimulin) along with bursicon and BMP antagonists were present. Synteny
      indicates that the GPHs, Grem, and SOSD have been maintained in a common gene
      neighborhood throughout much of metazoan evolution. The stable and highly
      conserved CKGFs are not identified in nonmetazoan organisms but are established
      with their receptors in the basal metazoans, becoming critical to growth,
      development, and regulation in all animals. 

PMID- 24904014
TI  - Analytical findings of an acute intoxication after inhalation of methoxetamine.
AB  - Methoxetamine (MXE) is increasingly used and abused, as it is frequently
      presented as being safer than ketamine, and legal. Cases of only MXE consumption
      being associated with the occurrence of seizures are rarely reported. A single
      MXE intoxication case by inhalation is described concerning a 21-year-old man,
      not known to be epileptic, who was found collapsed in his bedroom, supposedly
      after an epileptic seizure. He was transferred to the Emergency Department of the
      Henri Mondor Hospital, Aurillac, France. He was conscious, but with a sinus
      bradycardia (48/min) and an ST-segment elevation on the electrocardiogram, and a
      slightly increased creatine kinase level (270 U/L) and hyponatremia (127 mmol/L).
      New seizure activity occurred during hospitalization, but the clinical course in
      the intensive care unit was favorable. Quantitation of MXE in serum and urine
      using gas chromatography coupled to mass spectrometry (GC-MS) was developed, as
      well as a liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS)
      method for the determination of MXE in hair. Limits of detection and
      quantification were, respectively, 2 and 10 ug/L for the GC-MS method and both
      0.5 pg/mg for the LC-MS-MS method. Concentrations of 30 and 408 ug/L were,
      respectively, measured in serum and urine. Concentrations of 135 and 145 pg/mg
      were detected in two 2.5 cm hair strands, consistent with one or several
      consumptions during the 2 1/2 months prior to sampling. A sample of the powder
      consumed was available and also analyzed. This case illustrates the dangers of
      this drug, which justify its classification as a narcotic in France since August
      2013. 

PMID- 24904015
TI  - Pregnancy complicated by valvular heart disease: an update.

PMID- 24904016
TI  - Interventricular differences in beta-adrenergic responses in the canine heart:
      role of phosphodiesterases.
AB  - BACKGROUND: RV and LV have different embryologic, structural, metabolic, and
      electrophysiologic characteristics, but whether interventricular differences
      exist in beta-adrenergic (beta-AR) responsiveness is unknown. In this study, we
      examine whether beta-AR response and signaling differ in right (RV) versus left
      (LV) ventricles. METHODS AND RESULTS: Sarcomere shortening, Ca(2+) transients,
      ICa,L and IKs currents were recorded in isolated dog LV and RV midmyocytes.
      Intracellular [cAMP] and PKA activity were measured by live cell imaging using
      FRET-based sensors. Isoproterenol increased sarcomere shortening ~10-fold and
      Ca(2+)-transient amplitude ~2-fold in LV midmyocytes (LVMs) versus ~25-fold and
      ~3-fold in RVMs. FRET imaging using targeted Epac2camps sensors revealed no
      change in subsarcolemmal [cAMP], but a 2-fold higher beta-AR stimulation of
      cytoplasmic [cAMP] in RVMs versus LVMs. Accordingly, beta-AR regulation of ICa,L
      and IKs were similar between LVMs and RVMs, whereas cytoplasmic PKA activity was
      increased in RVMs. Both PDE3 and PDE4 contributed to the beta-AR regulation of
      cytoplasmic [cAMP], and the difference between LVMs and RVMs was abolished by
      PDE3 inhibition and attenuated by PDE4 inhibition. Finally LV and RV
      intracavitary pressures were recorded in anesthetized beagle dogs. A bolus
      injection of isoproterenol increased RV dP/dtmax~5-fold versus 3-fold in LV.
      CONCLUSION: Canine RV and LV differ in their beta-AR response due to intrinsic
      differences in myocyte beta-AR downstream signaling. Enhanced beta-AR
      responsiveness of the RV results from higher cAMP elevation in the cytoplasm, due
      to a decreased degradation by PDE3 and PDE4 in the RV compared to the LV.

PMID- 24904017
TI  - Patterns of care quality and prognosis among hospitalized ischemic stroke
      patients with chronic kidney disease.
AB  - BACKGROUND: Relatively little is known about the quality of care and outcomes for
      hospitalized ischemic stroke patients with chronic kidney disease (CKD). We
      examined quality of care and in-hospital prognoses among patients with CKD in the
      Get With The Guidelines-Stroke (GWTG-Stroke) program METHODS AND RESULTS: We
      analyzed 679 827 patients hospitalized with ischemic stroke from 1564 US centers
      participating in the GWTG-Stroke program between January 2009 and December 2012.
      Use of 7 predefined ischemic stroke performance measures, composite "defect-free"
      care compliance, and in-hospital mortality were examined based on glomerular
      filtration rate (GFR) categorized as a dichotomous (+CKD as <60) or rank-ordered
      variable: normal (>= 90), mild (>= 60 to <90), moderate (>= 30 to <60), severe
      (>= 15 to <30), and kidney failure (<15 or dialysis). There were 236 662 (35%)
      ischemic stroke patients with CKD. Patients with severe renal dysfunction or
      failure were significantly less likely to receive guideline-based therapies.
      Compared with patients with normal kidney function (>= 90), those with CKD
      (adjusted OR 0.91 [95% CI: 0.89 to 0.92]), moderate dysfunction (adjusted OR 0.94
      [95% CI: 0.92 to 0.97]), severe dysfunction (adjusted OR 0.80 [95% CI: 0.77 to
      0.84]), or failure (adjusted OR 0.72 [95% CI: 0.68 to 0.0.76]), were less likely
      to receive 100% defect-free care measure compliance. Inpatient mortality was
      higher for patients with CKD (adjusted odds ratio 1.44 [95% CI: 1.40 to 1.47]),
      and progressively rose with more severe renal dysfunction. CONCLUSIONS: Despite
      higher in-hospital mortality rates, ischemic stroke patients with CKD, especially
      those with greater severity of renal dysfunction, were less likely to receive
      important guideline-recommended therapies.

PMID- 24904020
TI  - Avoidable for whom? Hospital use at the end of life.

PMID- 24904019
TI  - Fine-mapping IGF1 and prostate cancer risk in African Americans: the multiethnic
      cohort study.
AB  - Genetic variation at insulin-like growth factor 1 (IGF1) has been linked to
      prostate cancer risk. However, the specific predisposing variants have not been
      identified. In this study, we fine-mapped the IGF1 locus for prostate cancer risk
      in African Americans. We conducted targeted Roche GS-Junior 454 resequencing of a
      156-kb region of IGF1 in 80 African American aggressive prostate cancer cases.
      Three hundred and thirty-four IGF1 SNPs were examined for their association with
      prostate cancer risk in 1,000 African American prostate cancer cases and 991
      controls. The top associated SNP in African Americans, rs148371593, was examined
      in an additional 3,465 prostate cancer cases and 3,425 controls of non-African
      American ancestry-European Americans, Japanese Americans, Latinos, and Native
      Hawaiians. The overall association of 334 IGF1 SNPs and prostate cancer risk was
      assessed using logistic kernel-machine methods. The association between each SNP
      and prostate cancer risk was evaluated through unconditional logistic regression.
      A false discovery rate threshold of q < 0.1 was used to determine statistical
      significance of associations. We identified 8 novel IGF1 SNPs. The cumulative
      effect of the 334 IGF1 SNPs was not associated with prostate cancer risk (P =
      0.13) in African Americans. Twenty SNPs were nominally associated with prostate
      cancer at P < 0.05. The top associated SNP among African Americans, rs148371593
      [minor allele frequency (MAF) = 0.03; P = 0.0014; q > 0.1], did not reach our
      criterion of statistical significance. This polymorphism was rare in non-African
      Americans (MAF < 0.003) and was not associated with prostate cancer risk (P =
      0.98). Our findings do not support the role of IGF1 variants and prostate cancer
      risk among African Americans.

PMID- 24904021
TI  - Serum uric acid and the risk of respiratory disease: a population-based cohort
      study.
AB  - INTRODUCTION: Uric acid is the most abundant molecule with antioxidant properties
      found in human blood serum. We examined the relationship between serum uric acid
      and the incidence of respiratory disease including any effect modification by
      smoking status. METHODS: A cohort with serum uric acid measured between 1 January
      2000 and 31 December 2012 was extracted from The Health Improvement Network
      primary care research database. New diagnoses of COPD and lung cancer were
      ascertained based on diagnostic codes entered into the medical records. RESULTS:
      During 1 002 496 person years (PYs) of follow-up, there were 3901 COPD diagnoses
      and 1015 cases of lung cancer. After multivariable adjustment, strong
      interactions with smoking status were detected (p<0.001) for both outcomes with
      significant negative relationships between serum uric acid and respiratory
      disease for current smokers but no strong relationships for never-smokers or ex
      smokers. The relationships were strongest for lung cancer in heavy smokers (>=20
      cigarettes per day) with predicted incidence rates 97 per 10 000 PYs (95% CI 68
      to 126) in the lowest serum uric acid quintile (100-250 umol/L) compared with a
      predicted 28 per 10 000 PYs (95% CI 14 to 41) in the highest quintile (438-700
      umol/L). CONCLUSIONS: Low levels of serum uric acid are associated with higher
      rates of COPD and lung cancer in current smokers after accounting for
      conventional risk factors.

PMID- 24904018
TI  - Cost-effectiveness of clopidogrel-aspirin versus aspirin alone for acute
      transient ischemic attack and minor stroke.
AB  - BACKGROUND: Treatment with the combination of clopidogrel and aspirin taken soon
      after a transient ischemic attack (TIA) or minor stroke was shown to reduce the
      90-day risk of stroke in a large trial in China, but the cost-effectiveness is
      unknown. This study sought to estimate the cost-effectiveness of the clopidogrel
      aspirin regimen for acute TIA or minor stroke. METHODS AND RESULTS: A Markov
      model was created to determine the cost-effectiveness of treatment of acute TIA
      or minor stroke patients with clopidogrel-aspirin compared with aspirin alone.
      Inputs for the model were obtained from clinical trial data, claims databases,
      and the published literature. The main outcome measure was cost per quality
      adjusted life-years (QALYs) gained. One-way and multivariable probabilistic
      sensitivity analyses were performed to test the robustness of the findings.
      Compared with aspirin alone, clopidogrel-aspirin resulted in a lifetime gain of
      0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental
      cost-effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic
      sensitivity analysis showed that clopidogrel-aspirin therapy was more cost
      effective in 95.7% of the simulations at a willingness-to-pay threshold
      recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per
      QALY. CONCLUSIONS: Early 90-day clopidogrel-aspirin regimen for acute TIA or
      minor stroke is highly cost-effective in China. Although clopidogrel is generic,
      Plavix is brand in China. If Plavix were generic, treatment with clopidogrel
      aspirin would have been cost saving.

PMID- 24904022
TI  - Replacing with whole grains and legumes reduces Lp-PLA2 activities in plasma and
      PBMCs in patients with prediabetes or T2D.
AB  - To determine dietary effects on circulating lipoprotein-associated phospholipase
      A2 (Lp-PLA2) activity and enzyme activity in peripheral blood mononuclear cells
      (PBMCs), 99 patients with impaired fasting glucose, impaired glucose tolerance,
      or newly-diagnosed T2D were randomly assigned to either a control group (usual
      diet with refined rice) or the whole grain and legume group. Substitution of
      whole grains and legumes for refined rice was associated with the replacement of
      7% of energy from carbohydrates with energy from protein (about 4%) and fat.
      After 12 weeks, the whole grain and legume group showed a significant decrease in
      fasting glucose, insulin, homeostasis model assessment-insulin resistance,
      hemoglobin A1c, malondialdehyde, plasma Lp-PLA2 activity, and oxidized LDL (ox
      LDL), and an increase in LDL particle size. The changes (Deltas) in these
      variables in the whole grain and legume group were significantly different from
      those in controls after adjustment for the baseline levels. When all subjects
      were considered, Delta plasma Lp-PLA2 positively correlated with Delta glucose,
      Delta PBMC Lp-PLA2, Delta ox-LDL, and Delta urinary 8-epi-prostaglandin F2alpha
      after being adjusted for confounding factors. The Delta PBMC Lp-PLA2 correlated
      positively with Delta glucose and Delta ox-LDL, and negatively with Delta LDL
      particle size and baseline PBMC Lp-PLA2 The substitution of whole grains and
      legumes for refined rice resulted in a reduction in Lp-PLA2 activities in plasma
      and PBMCs partly through improved glycemic control, increased consumption of
      protein relative to carbohydrate, and reduced lipid peroxides. 

PMID- 24904023
TI  - How long does secondhand smoke remain in household air: analysis of PM2.5 data
      from smokers' homes.
AB  - INTRODUCTION: More than 80% of secondhand smoke (SHS) is invisible to the human
      eye, and smokers are often unaware of how much SHS is produced when they smoke at
      home. Very little is known about how long SHS particles remain suspended in the
      air within household settings. METHODS: Data from a series of studies where fine
      particulate matter (PM2.5) concentrations were measured every minute in homes
      were used to identify the PM2.5 peak produced by SHS from the last cigarette
      smoked of the day. The time taken for this peak to reduce by 50% was calculated,
      as was the time between the peak and a return to the World Health Organization's
      (WHO) 24-hr guidance value for PM2.5 of 25 ug/m(3). RESULTS: From more than 230
      days worth of 1-min resolved PM2.5 data gathered from 103 smoking households, 140
      suitable peaks were identified. The median (interquartile range [IQR]) for the
      time for the SHS peak to decay by 50% was 55 (23-116) min, and the median (IQR)
      for the peak to reduce to the WHO guidance value for PM2.5 was 160 (90-313) min.
      CONCLUSIONS: SHS remains in household air for a considerable period after smoking
      a cigarette. This information is likely to be of use in public health information
      campaigns and in interventions to encourage smokers to make their home smoke
      free.

PMID- 24904024
TI  - Delayed prescribing for respiratory tract infections in primary care results in
      lower antibiotic use.

PMID- 24904025
TI  - Right-oriented bias: a comment on Roskes, Sligte, Shalvi, and De Dreu (2011).

PMID- 24904027
TI  - The importance of patient-reported outcomes: a call for their comprehensive
      integration in cardiovascular clinical trials.
AB  - Patient-reported outcomes (PROs), such as symptoms, health-related quality of
      life (HRQOL), or patient perceived health status, are reported directly by the
      patient and are powerful tools to inform patients, clinicians, and policy-makers
      about morbidity and 'patient suffering', especially in chronic diseases. Patient
      reported outcomes provide information on the patient experience and can be the
      target of therapeutic intervention. Patient-reported outcomes can improve the
      quality of patient care by creating a holistic approach to clinical decision
      making; however, PROs are not routinely used as key outcome measures in major
      cardiovascular clinical trials. Thus, limited information is available on the
      impact of cardiovascular therapeutics on PROs to guide patient-level clinical
      decision-making or policy-level decision-making. Cardiovascular clinical research
      should shift its focus to include PROs when evaluating the efficacy of
      therapeutic interventions, and PRO assessments should be scientifically rigorous.
      The European Society of Cardiology and other professional societies can take
      action to influence the uptake of PRO data in the research and clinical
      communities. This process of integrating PRO data into comprehensive efficacy
      evaluations will ultimately improve the quality of care for patients across the
      spectrum of cardiovascular disease. 

PMID- 24904026
TI  - Racial/Ethnic differences in medication uptake and clinical outcomes among
      hospitalized cardiovascular patients with hypertension and diabetes.
AB  - BACKGROUND: In the United States, hypertension and diabetes are more common among
      blacks and Hispanics than among others; the comorbidity is associated with worse
      clinical outcomes than each condition alone. Racial/ethnic differences in
      outcomes may be related to differential uptake of antihypertensive therapies, but
      data to evaluate this in real-world settings are limited. We aimed to determine
      the association between race/ethnicity and odds of rehospitalization or death,
      accounting for medication prescription, among a cohort of patients with
      hypertension and diabetes hospitalized for cardiovascular disease. METHODS: This
      was a 1-year prospective study of individuals that participated in a National
      Heart, Lung, and Blood Institute clinical outcomes study. Clinical/medication
      data and outcomes (rehospitalization and death at 30 days and at 1 year) were
      documented by electronic medical record, National Death Index, and standardized
      mail survey. Logistic regression was used to evaluate associations between
      race/ethnicity and outcomes adjusted for type of antihypertensive medication,
      demographics, and comorbidity. RESULTS: Participants (n = 1,126) were 14% black,
      28% Hispanic, and 58% white/other. A total of 611 (54%) participants were
      rehospitalized at 1 year. Predictors of rehospitalization at 1 year included
      Hispanic ethnicity, diuretic prescription, lack of health insurance, peripheral
      vascular disease, and heart failure (P < 0.05). Race/ethnicity was not associated
      with rehospitalization at 30 days or death at 30 days or at 1 year. Increased
      odds of rehospitalization at 1 year among Hispanics remained significant after
      multivariable adjustment (odds ratio = 1.6; 95% confidence interval = 1.2-2.1).
      CONCLUSIONS: In this study of hospitalized hypertension patients with diabetes,
      Hispanics had higher odds of rehospitalization than whites/others at 1 year but
      not at 30 days, and this was not explained by type of antihypertension medication
      prescribed.

PMID- 24904029
TI  - New EU clinical trials regulation.

PMID- 24904028
TI  - Nitrite transport activity of a novel HPP family protein conserved in
      cyanobacteria and chloroplasts.
AB  - Some cyanobacterial genomes encode an integral membrane protein of the HPP
      family, which exhibited nitrite transport activity when expressed in the nitrite
      transport-less NA4 mutant of the cyanobacterium Synechococcus elongatus strain
      PCC 7942. AT5G62720 and AT3G47980 were found to encode Arabidopsis homologs of
      the cyanobacterial protein. The product of AT5G62720 was localized to the
      chloroplast envelope membrane and was shown to confer nitrite uptake activity on
      the NA4 mutant when expressed with an N-terminally truncated transit peptide or
      as a fusion with the N-terminal region of the cyanobacterial HPP family protein.
      Kinetic analyses showed that the Arabidopsis protein has much higher affinity for
      nitrite (K(m) = 13 uM) than the cyanobacterial protein (K(m) = 150 uM).
      Illuminated chloroplasts isolated from the mutant lines of AT5G62720 showed much
      lower activity of nitrite uptake than the chloroplasts isolated from the wild
      type Col-0 plants, while the chloroplasts of the mutants of AT1G68570 (AtNPF3.1),
      the gene previously reported to encode a plastid nitrite transporter AtNitr1,
      showed wild-type levels of nitrite uptake activity. AT3G47980 was expressed in
      roots but not in shoots. It has a putative transit peptide similar to that of
      AT5G62720 and its fusion with the N-terminal region of the cyanobacterial HPP
      protein showed low but significant activity of nitrite transport in the
      cyanobacterial cell. Transcription of AT5G62720 (AtNITR2;1) and AT3G47980
      (AtNITR2;2) was stimulated by nitrate under the control of the NIN-like proteins,
      suggesting that the HPP proteins represent nitrate-inducible components of the
      nitrite transport system of plastids.

PMID- 24904030
TI  - Life after work: a doctor's lonely hearts club.

PMID- 24904031
TI  - London GPs march to protest against phase-out of protection for practice funding.

PMID- 24904032
TI  - European Ombudsman ramps up action against European Medicines Agency over data
      transparency plans.

PMID- 24904033
TI  - Obama administration highlights health benefits of carbon plan.

PMID- 24904034
TI  - World Cup is set to make many Chinese workers "sick".

PMID- 24904035
TI  - Local councils call for more money for integrating care.

PMID- 24904036
TI  - Multimodality imaging for pre-clinical assessment of Fabry's cardiomyopathy.
AB  - Anderson Fabry's disease (AFD) is a rare but underdiagnosed intracellular lipid
      disorder which can cause left ventricular hypertrophy (LVH). Pre-clinical
      diagnosis of Fabry's disease is important as it permits early stratification for
      enzyme replacement therapy, improving the patient's long-term prognosis, avoiding
      progression to irreversible fibrosis, and preventing cardiovascular
      complications. Combinations of imaging modalities that integrate the strengths of
      each modality and at the same time eliminate weaknesses of an individual modality
      can offer improved diagnostics, therapeutic monitoring, and pre-clinical
      assessment of Fabry's disease. This review discusses the advantages and
      challenges in developing multimodality imaging systems of Fabry's cardiomyopathy,
      highlights some successful combinations that are now routinely used in the clinic
      and in research, and discusses recent advances in multimodality instrumentation
      that may offer new opportunities for pre-clinical assessment of this disease. 

PMID- 24904037
TI  - Aggression Among Psychiatric Inpatients: The Relationship Between Time, Place,
      Victims, and Severity Ratings.
AB  - BACKGROUND: The rate of aggressive acts perpetrated by psychiatric inpatients
      remains a pressing issue. To date, few studies have distinguished between
      incident severities. OBJECTIVE: The aims of the current study were to identify
      rates of inpatient aggression in an inpatient forensic psychiatric facility and
      describe the severity of the aggression reported for aggressive incidents.
      DESIGN: All documented acts of aggression at a 1,500-bed forensic hospital
      between 2009 and 2013 provided data about the time, location, and victims of
      aggressive acts. In total, 52,109 unique incidents were analyzed. RESULTS: The
      findings showed an increase in violence rates during meal, medication, and shift
      change times. Patients (n = 3,436, 62%) were victimized more often than staff
      members (n = 2,103, 38%). Fall and winter months showed more acts of aggression
      than summer and spring, but there were no mean differences between severity
      ratings by season. The results showed that the swing shift saw more severe
      aggressive incidents than the morning or overnight shifts, p = .001, and
      significantly more serious incidents occurred when there were staff members
      working over time, p = .050. CONCLUSIONS: The current study reports some key
      findings about aggression rates with a very large sample and presents some
      valuable data regarding the severity of aggressive acts.

PMID- 24904038
TI  - Using Findings From the Human Rights Authority Reports to Inform Psychiatric
      Nursing Practice.
AB  - BACKGROUND: In Illinois, the Human Rights Authority (HRA) exists to conduct
      investigations of complaints of violations of the rights of persons with
      disabilities. PURPOSE OF STUDY: The purpose of this study is to describe the
      findings from the HRA investigations and to determine significant implications
      for psychiatric nursing practice. METHOD: A descriptive cross-sectional design
      was used, and the sample was composed of reports from the Illinois Guardianship &
      Advocacy Commission HRA (N = 129) for 2008. RESULTS: Allegations of
      restriction/notification of rights were significantly more likely to be
      substantiated than other allegation types. State hospitals were less likely to
      have allegations against them, whereas medical hospitals were less likely to have
      inadequate treatment allegations and more likely to have restriction/notification
      of rights allegations. CONCLUSIONS: The HRA findings will inform psychiatric
      nursing practice by expanding the nurses' knowledge of patient rights issues.

PMID- 24904039
TI  - A Pilot Study of the Psychological Impact of the Great East Japan Earthquake and
      Tsunami.
AB  - BACKGROUND: There is evidence that a large-scale disaster may have indirect
      psychological impact on the individuals who were not involved with the disaster
      first hand. The 2011 earthquake and tsunami disasters in Japan provide an
      opportunity to investigate the potential global effect of indirect exposure
      associated with intense media coverage. OBJECTIVES: To compare the disaster's
      psychological impact between Japanese and non-Japanese students; to determine
      what factors are associated with higher psychological impact. DESIGN: A cross
      sectional, anonymous online survey of university students in the Midwest.
      RESULTS: Japanese students scored significantly higher on the Impact of Event
      Scale-Revised (IES-R) hyperarousal subscale compared with non-Japanese students.
      Those who were in Japan when the disaster occurred exhibited significantly higher
      psychological impact levels. There were significant correlations between media
      exposure and two IES-R subscales: avoidance and hyperarousal. CONCLUSIONS: The
      results support the finding from 9/11 studies that indirect exposure is
      associated with stress-related psychological responses.

PMID- 24904041
TI  - Using Tweets to Facilitate the Conversation About Evidence-Based Psychiatric and
      Mental Health Care.

PMID- 24904040
TI  - APNA Board of Directors' Column.

PMID- 24904042
TI  - Conditional Auxin Response and Differential Cytokinin Profiles in Shoot Branching
      Mutants.
AB  - Strigolactone (SL), auxin, and cytokinin (CK) are hormones that interact to
      regulate shoot branching. For example, several ramosus (rms) branching mutants in
      pea (Pisum sativum) have SL defects, perturbed xylem CK levels, and diminished
      responses to auxin in shoot decapitation assays. In contrast with the last of
      these characteristics, we discovered that buds on isolated nodes (explants) of
      rms plants instead respond normally to auxin. We hypothesized that the presence
      or absence of attached roots would result in transcriptional and hormonal
      differences in buds and subtending stem tissues, and might underlie the
      differential auxin response. However, decapitated plants and explants both showed
      similar up-regulation of CK biosynthesis genes, increased CK levels, and down
      regulation of auxin transport genes. Moreover, auxin application counteracted
      these trends, regardless of the effectiveness of auxin at inhibiting bud growth.
      Multivariate analysis revealed that stem transcript and CK changes were largely
      associated with decapitation and/or root removal and auxin response, whereas bud
      transcript profiles related more to SL defects. CK clustering profiles were
      indicative of additional zeatin-type CKs in decapitated stems being supplied by
      roots and thus promoting bud growth in SL-deficient genotypes even in the
      presence of added auxin. This difference in CK content may explain why rms buds
      on explants respond better to auxin than those on decapitated plants. We further
      conclude that rapid changes in CK status in stems are auxin dependent but largely
      SL independent, suggesting a model in which auxin and CK are dominant regulators
      of decapitation-induced branching, whereas SLs are more important in intact
      plants.

PMID- 24904044
TI  - Cultivating a narrative sensibility in nursing practice.
AB  - Stories hold meaning, and when persons tell of their experiences of living with
      illness, they are afforded an opportunity to make sense of all that is happening.
      As nurses, we have the privilege of hearing the particular, gaining
      understanding, and creating a powerful encounter that has healing and health
      benefits. This is a call for nurses to more intentionally invite and listen to
      the stories of persons living with illness. The mnemonic STORIED is offered to
      help nurses weave together essential elements of a narrative practice approach:
      Subjective, Tell/Listen, Openness, Reflection, Invite/Intention, Engage, and
      Document. Nurses are the voice of the vulnerable, and to learn to listen to our
      patients' stories such that what is gleaned contributes to their healing is
      nothing less than a call to excellent care of the unique person before us. 

PMID- 24904045
TI  - Genomic evidence for adaptation by gene duplication.
AB  - Gene duplication is widely believed to facilitate adaptation, but unambiguous
      evidence for this hypothesis has been found in only a small number of cases.
      Although gene duplication may increase the fitness of the involved organisms by
      doubling gene dosage or neofunctionalization, it may also result in a simple
      division of ancestral functions into daughter genes, which need not promote
      adaptation. Hence, the general validity of the adaptation by gene duplication
      hypothesis remains uncertain. Indeed, a genome-scale experiment found similar
      fitness effects of deleting pairs of duplicate genes and deleting individual
      singleton genes from the yeast genome, leading to the conclusion that duplication
      rarely results in adaptation. Here we contend that the above comparison is unfair
      because of a known duplication bias among genes with different fitness
      contributions. To rectify this problem, we compare homologous genes from the
      budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces
      pombe. We discover that simultaneously deleting a duplicate gene pair in S.
      cerevisiae reduces fitness significantly more than deleting their singleton
      counterpart in S. pombe, revealing post-duplication adaptation. The duplicates
      singleton difference in fitness effect is not attributable to a potential
      increase in gene dose after duplication, suggesting that the adaptation is owing
      to neofunctionalization, which we find to be explicable by acquisitions of binary
      protein-protein interactions rather than gene expression changes. These results
      provide genomic evidence for the role of gene duplication in organismal
      adaptation and are important for understanding the genetic mechanisms of
      evolutionary innovation. 

PMID- 24904047
TI  - Musculoskeletal symptoms and orthopaedic complications in pregnancy:
      pathophysiology, diagnostic approaches and modern management.
AB  - Low back pain is a common musculoskeletal symptom in pregnancy that can present
      as lumbar pain or pelvic girdle pain, with significant physical and psychosocial
      implications. Pelvic girdle pain is more prevalent and results in greater
      disability than lumbar pain. It is possible to distinguish between these two
      conditions from a detailed history based on the site of the pain, its intensity,
      disability and pain provocation tests. Management of low back pain in pregnancy
      is conservative, with physical exercise for lumbar pain and minimising activities
      that exacerbate pain, analgesics and bed rest for pelvic girdle pain, as well as
      avoiding abduction beyond the pain-free zone in labour. There is evidence that
      stabilising exercises in patients with pelvic girdle pain postpartum have a
      beneficial effect. Other treatment modalities that have been shown to be safe and
      effective include pelvic belts, transcutaneous electrical nerve stimulation,
      spinal manipulative therapy, acupuncture and complementary therapy with yoga.
      Other orthopaedic complications in pregnancy such as carpal tunnel syndrome,
      pubic symphysis rupture, transient osteoporosis and osteonecrosis are usually
      self-limiting with a satisfactory outcome. However, a lack of awareness and
      failure to recognise these complications can result in long-term morbidity.
      Knowledge of the preoperative diagnostic investigations, surgical approaches and
      intraoperative positioning of the mother to avoid gravid uterus compression is
      vital in orthopaedic emergencies such as lumbar disc herniation, cauda equina
      syndrome, fractures and acute compartment syndrome of the lower limb to ensure a
      safe maternal and fetal outcome and to prevent serious disability. Pregnancy is
      not contraindicated in women with pre-existing orthopaedic complications such as
      kyphoscoliosis and total hip arthroplasty as there is no evidence to suggest
      increased maternal or fetal risks. 

PMID- 24904046
TI  - Digital expression profiling of the compartmentalized translatome of Purkinje
      neurons.
AB  - Underlying the complexity of the mammalian brain is its network of neuronal
      connections, but also the molecular networks of signaling pathways, protein
      interactions, and regulated gene expression within each individual neuron. The
      diversity and complexity of the spatially intermingled neurons pose a serious
      challenge to the identification and quantification of single neuron components.
      To address this challenge, we present a novel approach for the study of the
      ribosome-associated transcriptome-the translatome-from selected subcellular
      domains of specific neurons, and apply it to the Purkinje cells (PCs) in the rat
      cerebellum. We combined microdissection, translating ribosome affinity
      purification (TRAP) in nontransgenic animals, and quantitative nanoCAGE
      sequencing to obtain a snapshot of RNAs bound to cytoplasmic or rough endoplasmic
      reticulum (rER)-associated ribosomes in the PC and its dendrites. This allowed us
      to discover novel markers of PCs, to determine structural aspects of genes, to
      find hitherto uncharacterized transcripts, and to quantify biophysically relevant
      genes of membrane proteins controlling ion homeostasis and neuronal electrical
      activities. 

PMID- 24904048
TI  - Correlates of Knowledge of HIV Transmission Among Incident Cases of HIV in a
      Cohort of Injection Drug Users Receiving Harm Reduction Services at Karachi,
      Pakistan.
AB  - BACKGROUND: Knowledge of risk factors for HIV transmission in high-risk
      population plays a critical role in averting the risk of HIV transmission. In
      Pakistan, injection drug users (IDUs) constitute the core risk group of HIV
      prevalence, where the epidemic has transitioned to a "concentrated level." Still
      nothing is known about the role of knowledge in HIV transmission and HIV sero
      conversion among IDUs in Pakistan. METHODS: From 2009 to 2011, a nested case
      control study was conducted in a cohort of 636 IDUs receiving harm reduction
      services in the mega city of Karachi. RESULTS: In multivariable regression
      analysis, 3 factors, namely HIV does not spread through unprotected sex (adjusted
      odds ratio [AOR]: 3.1, 95% confidence interval [CI] 1.39-6.90, P value .01), HIV
      does not transmit by sharing syringes (AOR: 3.5, 95% CI 1.97-6.40, P value <.00),
      and the risk of HIV cannot be minimized by using new syringe every time (AOR:
      2.0, 95% CI 1.16-3.60, P value .01), were significantly associated with the
      incident cases of HIV. CONCLUSION: The study findings suggest the association
      between knowledge of HIV transmission and HIV sero-incident cases.

PMID- 24904049
TI  - Source Memory for Self and Other in Patients With Mild Cognitive Impairment due
      to Alzheimer's Disease.
AB  - OBJECTIVES: The present study examined the role of enactment in source memory in
      a cognitively impaired population. As seen in healthy older adults, it was
      predicted that source memory in people with mild cognitive impairment due to
      Alzheimer's disease (MCI-AD) would benefit from the self-reference aspect of
      enactment. METHOD: Seventeen participants with MCI-AD and 18 controls worked in
      small groups to pack a picnic basket and suitcase and were later tested for their
      source memory for each item. RESULTS: For item memory, self-referencing improved
      corrected recognition scores for both MCI-AD and control participants. The MCI-AD
      group did not demonstrate the same benefit as controls in correct source memory
      for self-related items. However, those with MCI-AD were relatively less likely to
      misattribute new items to the self and more likely to misattribute new items to
      others when committing errors, compared with controls. DISCUSSION: The enactment
      effect and self-referencing did not enhance accurate source memory more than
      other referencing for patients with MCI-AD. However, people with MCI-AD benefited
      in item memory and source memory, being less likely to falsely claim new items as
      their own, indicating some self-reference benefit occurs for people with MCI-AD.

PMID- 24904050
TI  - Endovascular treatment of internal carotid artery bifurcation aneurysms: a single
      center experience and a systematic review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Endovascular coiling of internal carotid artery
      bifurcation aneurysms can be challenging due to unfavorable morphologic features.
      With improvements in endovascular techniques, several series have detailed the
      results and complications of endovascular treatment of aneurysms at this
      location. We performed a systematic review and meta-analysis of published series
      on the endovascular treatment of ICA bifurcation aneurysms, including a tertiary
      referral center experience. MATERIALS AND METHODS: We performed a comprehensive
      literature search for reports on contemporary endovascular treatment of ICA
      bifurcation aneurysms from 2000 to 2013, and we reviewed our experience. We
      extracted information regarding periprocedural complications, procedure-related
      morbidity and mortality, immediate angiographic outcome, long-term clinical and
      angiographic outcome, and retreatment rate. Event rates were pooled across
      studies by using random-effects meta-analysis. RESULTS: Including our series of
      37 patients, 6 studies with 158 patients were analyzed. Approximately 60% of the
      aneurysms presented as unruptured; 88.0% (95% CI, 68.0%-96.0%) of aneurysms
      showed complete or near-complete occlusion at immediate postoperative angiography
      compared with 82.0% (95% CI, 73.0%-88.0%) at last follow-up. The procedure
      related morbidity and mortality were 3.0% (95% CI, 1.0%-7.0%) and 3.0% (95% CI,
      1.0%-8.0%), respectively. The retreatment rate was 14.0% (95% CI, 8.0%-25.0%).
      Good neurologic outcome was achieved in 93.0% (95% CI, 86.0%-97.0%) of patients.
      CONCLUSIONS: Endovascular treatment of ICA bifurcation aneurysms is feasible and
      effective and is associated with high immediate angiographic occlusion rates.
      However, retreatment rates and procedure-related morbidity and mortality are non
      negligible.

PMID- 24904051
TI  - Dynamic CT for parathyroid disease: are multiple phases necessary?
AB  - BACKGROUND AND PURPOSE: A 4D CT protocol for detection of parathyroid lesions
      involves obtaining unenhanced, arterial, early, and delayed venous phase images.
      The aim of the study was to determine the ideal combination of phases that would
      minimize radiation dose without sacrificing diagnostic accuracy. MATERIALS AND
      METHODS: With institutional review board approval, the records of 29 patients
      with primary hyperparathyroidism who had undergone surgical exploration were
      reviewed. Four neuroradiologists who were blinded to the surgical outcome
      reviewed the imaging studies in 5 combinations (unenhanced and arterial phase;
      unenhanced, arterial, and early venous; all 4 phases; arterial alone; arterial
      and early venous phases) with an interval of at least 7 days between each review.
      The accuracy of interpretation in lateralizing an abnormality to the side of the
      neck (right, left, ectopic) and localizing it to a quadrant in the neck (right or
      left upper, right or left lower) was evaluated. RESULTS: The lateralization and
      localization accuracy (90.5% and 91.5%, respectively) of the arterial phase alone
      was comparable with the other combinations of phases. There was no statistically
      significant difference among the different combinations of phases in their
      ability to lateralize or localize adenomas to a quadrant (P = .976 and .996,
      respectively). CONCLUSIONS: Assessment of a small group of patients shows that
      adequate diagnostic accuracy for parathyroid adenoma localization may be
      achievable by obtaining arterial phase images alone. If this outcome can be
      validated prospectively in a larger group of patients, then the radiation dose
      can potentially be reduced to one-fourth of what would otherwise be administered.

PMID- 24904052
TI  - Value of 4D MR angiography at 3T compared with DSA for the follow-up of treated
      brain arteriovenous malformation.
AB  - BACKGROUND AND PURPOSE: Four-dimensional, contrast-enhanced MRA is a useful
      technique for the diagnosis and classification of brain AVM. The purpose of this
      study was to evaluate its usefulness in the follow-up of treated brain AVM.
      MATERIALS AND METHODS: Patients with treated brain AVM (embolization,
      radiosurgery, and/or surgery) were investigated with both DSA (the "gold
      standard") and 4D MRA. Four-dimensional MRA was performed at 3T using a 4D
      sequence, combining contrast-enhanced timing-robust angiography, keyhole, and
      sensitivity encoding techniques. Examinations were evaluated by 2 independent
      readers and disagreements were resolved by a third reader. Interobserver and
      intermodality agreement with respect to residual nidus, residual venous drainage,
      and brain AVM patency were determined. RESULTS: Between May 2008 and February
      2013, 37 patients with a median age of 45 years (interquartile range = 26-55)
      were prospectively included. Examinations were acquired 36 months (IQR = 10-45.5)
      after the last treatment. Interobserver agreement for brain AVM patency was very
      good for both 4D MRA (kappa 0.82, 95% CI .67-.98) and DSA (kappa 0.84, 95% CI .69
      .98). After consensus reading, intermodality agreement for the evaluation of
      brain AVM patency was good (kappa 0.73, 95% CI .55-.90). Diagnostic accuracy of
      4D MRA for residual brain AVM compared with DSA, reached a sensitivity of 73.7%,
      specificity 100%, positive predictive value 100%, and negative predictive value
      78.3%. Agreements by technique of treatment are also detailed. CONCLUSIONS: Four
      dimensional MRA is a useful radiation-free technique for the follow-up of
      patients with treated brain AVM, especially patients treated by radiosurgery.
      However, given its actual limitations it is not sufficient to assert the cure;
      DSA remains mandatory for this purpose.

PMID- 24904053
TI  - The role of functional dopamine-transporter SPECT imaging in parkinsonian
      syndromes, part 1.
AB  - SUMMARY: As we defeat infectious diseases and cancer, one of the greatest medical
      challenges facing us in the mid-21st century will be the increasing prevalence of
      degenerative disease. Those diseases, which affect movement and cognition, can be
      the most debilitating. Dysfunction of the extrapyramidal system results in
      increasing motor disability often manifest as tremor, bradykinesia, and rigidity.
      The common pathologic pathway of these diseases, collectively described as
      parkinsonian syndromes, such as Parkinson disease, multiple system atrophy,
      progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy
      bodies, is degeneration of the presynaptic dopaminergic pathways in the basal
      ganglia. Conventional MR imaging is insensitive, especially in early disease, so
      functional imaging has become the primary method used to differentiate a true
      parkinsonian syndrome from vascular parkinsonism, drug-induced changes, or
      essential tremor. Unusually for a modern functional imaging technique, the method
      most widely used in European clinics depends on SPECT and not PET. This SPECT
      technique (described in the first of 2 parts) commonly reports dopamine
      transporter function, with decreasing striatal uptake demonstrating increasingly
      severe disease.

PMID- 24904054
TI  - Evaluation of the pontine perforators of the basilar artery using digital
      subtraction angiography in high resolution and 3D rotation technique.
AB  - BACKGROUND AND PURPOSE: Compromise of perforating branches of the basilar artery
      resulting in brain stem infarctions has been described as a major complication of
      intracranial stent placement for basilar artery stenosis or after implantation of
      endovascular flow diverters. Descriptions of pontine arteries are mainly based on
      examinations of injection specimens; however, there is a lack of consistent
      presentation of the small branches of the basilar artery in the imaging
      literature. Therefore, we retrospectively analyzed DSA images and 3D rotational
      angiography with a review of literature for an imaging definition of
      microvascular anatomy of the brain stem. MATERIALS AND METHODS: We
      retrospectively analyzed 2k DSA images (detector format 32 * 32 cm; image matrix
      2480 * 1920 pixels) and 3D rotational angiography reconstructions (5 second DSA,
      subtraction technique) obtained on Axiom Artis zee biplane neuroradiologic
      angiography equipment using standard protocol. RESULTS: On 2D and 3D DSA images,
      small arterial side branches of the basilar artery can be demonstrated in each of
      the cases but with a wide variation in the visibility of these vessels. Compared
      with 2D DSA images, 3D DSA reconstructions allow superior visualization of the
      small branches of the basilar artery. CONCLUSIONS: Our results demonstrate that
      2D DSA and 3D-rotation techniques are able to reliably visualize the penetrating
      branches of the brain stem in vivo. No zone of basilar artery is free from
      important side branches. Collateral pathways between circumferential and
      perforating arteries are occasionally detectable. In the future, further
      refinement of imaging techniques is necessary to increase the reliability of
      small vessel angiography to use this data for risk assessment before stent
      placement and aneurysm treatment.

PMID- 24904055
TI  - Role of New Diagnosis, Social Isolation, and Depression in Older Adults' Smoking
      Cessation.
AB  - PURPOSE OF THE STUDY: Though older adults smoke at a lower rate than younger
      adults, cessation can be difficult, especially after years of smoking. This paper
      examined the influence of a diagnosis of chronic illness, social isolation, and
      depression on smoking cessation among the most recent cohort of older smokers who
      were representative of U.S. Medicare beneficiaries. DESIGN AND METHODS: We used
      data from the 2011 (T1) and 2012 (T2) interview waves of the U.S. National Health
      and Aging Trends Study. Multivariate regression models examined correlates of T1
      smoking status (never smoker, former smoker, and current smoker; n = 6,680) and
      predictors of T2 smoking status among T1 smokers (quit smoking vs. continued
      smoking; n = 412). RESULTS: At T1, 8.8%, 44.7%, and 46.5% of the sample,
      respectively, were current, former, and never smokers. Current smokers had lower
      socioeconomic status, were more socially isolated, and had higher depressive
      symptoms than never smokers. At T2, 88.9% of T1 smokers continued smoking and
      11.1% no longer smoked. The odds of smoking cessation increased with a new
      diagnosis of chronic illness since T1 and decreased with a higher number of
      cigarettes smoked at T1. Social isolation at T1 increased the odds of smoking
      cessation, but depressive symptoms at T1 were not a significant factor.
      IMPLICATIONS: Heavy-smoking older adults may require extended pharmachotherapy
      and counseling. As newly diagnosed health problems can be a trigger for smoking
      cessation, health care providers can motivate and help older adults quit (or
      reduce) smoking as an integral part of their practices.

PMID- 24904057
TI  - Parathyroid hormone regulates histone deacetylase (HDAC) 4 through protein kinase
      A-mediated phosphorylation and dephosphorylation in osteoblastic cells.
AB  - Histone deacetylases (HDACs) are crucial regulators of gene expression in
      transcriptional co-repressor complexes. Previously, we reported that HDAC4 was a
      basal repressor of matrix metalloproteinase-13 (MMP-13) transcription and
      parathyroid hormone (PTH) regulates HDAC4 to control MMP-13 promoter activity
      through dissociation from Runx2. Here, we show that PTH induces the protein
      kinase A (PKA)-dependent phosphorylation of HDAC4 in the nucleus of the rat
      osteoblastic cell line, UMR 106-01. We demonstrate that PKA-dependent
      phosphorylated HDAC4 is released from Runx2 bound to the MMP-13 promoter in these
      cells. Point mutation of Ser-740 in rHDAC4 prevents the release of HDAC4 from
      Runx2 on the MMP-13 promoter and also prevents the PTH stimulation of MMP-13
      transcription. Thus, PTH-induced phosphorylation of rHDAC4 at Ser-740 is crucial
      for regulating MMP-13 transcription in osteoblasts. PTH causes degradation of
      HDAC4, and this product appears in the cytoplasm. The cytoplasmic degradation of
      HDAC4 is blocked by PKA and lysosomal inhibitors, but is not affected by
      proteasome, caspase-3, or serine and aspartic protease inhibitors. In addition,
      the phosphatase inhibitor, okadaic acid, prevents degradation indicating that
      dephosphorylation is associated with degradation. These mechanisms regulating
      HDAC4 and their roles in such processes are crucial for bone and chondrocyte
      development. Our data support a link between PTH regulating HDAC4 phosphorylation
      by PKA, trafficking, partial degradation, and the control of MMP-13 transcription
      through association with Runx2. 

PMID- 24904056
TI  - FbsC, a novel fibrinogen-binding protein, promotes Streptococcus agalactiae-host
      cell interactions.
AB  - Streptococcus agalactiae (group B Streptococcus or GBS) is a common cause of
      invasive infections in newborn infants and adults. The ability of GBS to bind
      human fibrinogen is of crucial importance in promoting colonization and invasion
      of host barriers. We characterized here a novel fibrinogen-binding protein of
      GBS, designated FbsC (Gbs0791), which is encoded by the prototype GBS strain
      NEM316. FbsC, which bears two bacterial immunoglobulin-like tandem repeat domains
      and a C-terminal cell wall-anchoring motif (LPXTG), was found to be covalently
      linked to the cell wall by the housekeeping sortase A. Studies using recombinant
      FbsC indicated that it binds fibrinogen in a dose-dependent and saturable manner,
      and with moderate affinity. Expression of FbsC was detected in all clinical GBS
      isolates, except those belonging to the hypervirulent lineage ST17. Deletion of
      fbsC decreases NEM316 abilities to adhere to and invade human epithelial and
      endothelial cells, and to form biofilm in vitro. Notably, bacterial adhesion to
      fibrinogen and fibrinogen binding to bacterial cells were abolished following
      fbsC deletion in NEM316. Moreover, the virulence of the fbsC deletion mutant and
      its ability to colonize the brain were impaired in murine models of infection.
      Finally, immunization with recombinant FbsC significantly protected mice from
      lethal GBS challenge. In conclusion, FbsC is a novel fibrinogen-binding protein
      expressed by most GBS isolates that functions as a virulence factor by promoting
      invasion of epithelial and endothelial barriers. In addition, the protein has
      significant immunoprotective activity and may be a useful component of an anti
      GBS vaccine.

PMID- 24904058
TI  - Amigo adhesion protein regulates development of neural circuits in zebrafish
      brain.
AB  - The Amigo protein family consists of three transmembrane proteins characterized
      by six leucine-rich repeat domains and one immunoglobulin-like domain in their
      extracellular moieties. Previous in vitro studies have suggested a role as
      homophilic adhesion molecules in brain neurons, but the in vivo functions remain
      unknown. Here we have cloned all three zebrafish amigos and show that amigo1 is
      the predominant family member expressed during nervous system development in
      zebrafish. Knockdown of amigo1 expression using morpholino oligonucleotides
      impairs the formation of fasciculated tracts in early fiber scaffolds of brain. A
      similar defect in fiber tract development is caused by mRNA-mediated expression
      of the Amigo1 ectodomain that inhibits adhesion mediated by the full-length
      protein. Analysis of differentiated neural circuits reveals defects in the
      catecholaminergic system. At the behavioral level, the disturbed formation of
      neural circuitry is reflected in enhanced locomotor activity and in the inability
      of the larvae to perform normal escape responses. We suggest that Amigo1 is
      essential for the development of neural circuits of zebrafish, where its
      mechanism involves homophilic interactions within the developing fiber tracts and
      regulation of the Kv2.1 potassium channel to form functional neural circuitry
      that controls locomotion. 

PMID- 24904060
TI  - Amino Acid Uptake and Metabolism of Legionella pneumophila Hosted by Acanthamoeba
      castellanii.
AB  - Legionella pneumophila survives and replicates within a Legionella-containing
      vacuole (LCV) of amoebae and macrophages. Less is known about the carbon
      metabolism of the bacteria within the LCV. We have now analyzed the transfer and
      usage of amino acids from the natural host organism Acanthamoeba castellanii to
      Legionella pneumophila under in vivo (LCV) conditions. For this purpose, A.
      castellanii was 13C-labeled by incubation in buffer containing [U
      (13)C(6)]glucose. Subsequently, these 13C-prelabeled amoebae were infected with
      L. pneumophila wild type or some mutants defective in putative key enzymes or
      regulators of carbon metabolism. 13C-Isotopologue compositions of amino acids
      from bacterial and amoebal proteins were then determined by mass spectrometry. In
      a comparative approach, the profiles documented the efficient uptake of
      Acanthamoeba amino acids into the LCV and further into L. pneumophila where they
      served as precursors for bacterial protein biosynthesis. More specifically, A.
      castellanii synthesized from exogenous [U-13C6]glucose unique isotopologue
      mixtures of several amino acids including Phe and Tyr, which were also observed
      in the same amino acids from LCV-grown L. pneumophila. Minor but significant
      differences were only detected in the isotopologue profiles of Ala, Asp, and Glu
      from the amoebal or bacterial protein fractions, respectively, indicating partial
      de novo synthesis of these amino acids by L. pneumophila. The similar
      isotopologue patterns in amino acids from L. pneumophila wild type and the
      mutants under study reflected the robustness of amino acid usage in the LCV of A.
      castellannii.

PMID- 24904059
TI  - Regulation of Fc?RI signaling in mast cells by G protein-coupled receptor kinase
      2 and its RH domain.
AB  - Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) by
      GPCRkinases (GRKs) promotes their desensitization and internalization. Here, we
      sought to determine the role of GRK2 on Fc?RI signaling and mediator release in
      mast cells. The strategies utilized included lentiviral shRNA-mediated GRK2
      knockdown, GRK2 gene deletion (GRK2(flox/flox)/cre recombinase) and
      overexpression of GRK2 and its regulator of G protein signaling homology (RH)
      domain (GRK2-RH). We found that silencing GRK2 expression caused ~50% decrease in
      antigen-induced Ca(2+) mobilization and degranulation but resulted in ablation of
      cytokine (IL-6 and IL-13) generation. The effect of GRK2 on cytokine generation
      does not require its catalytic activity but is mediated via the phosphorylation
      of p38 and Akt. Overexpression of GRK2 or its RH domain (GRK2-RH) enhanced
      antigen-induced mast cell degranulation and cytokine generation without affecting
      the expression levels of any of the Fc?RI subunits (alpha, beta, and gamma). GRK2
      or GRK2-RH had no effect on antigen-induced phosphorylation of Fc?RIgamma or Src
      but enhanced tyrosine phosphorylation of Syk. These data demonstrate that GRK2
      modulates Fc?RI signaling in mast cells via at least two mechanisms.One involves
      GRK2-RH and modulates tyrosine phosphorylation of Syk, and the other is mediated
      via the phosphorylation of p38 and Akt.

PMID- 24904061
TI  - Substitution of NS5 N-terminal domain of dengue virus type 2 RNA with type 4
      domain caused impaired replication and emergence of adaptive mutants with
      enhanced fitness.
AB  - Flavivirus NS3 and NS5 are required in viral replication and 5'-capping. NS3 has
      NS2B-dependent protease, RNA helicase, and 5'-RNA triphosphatase activities. NS5
      has 5'-RNA methyltransferase (MT)/guanylyltransferase (GT) activities within the
      N-terminal 270 amino acids and the RNA-dependent RNA polymerase (POL) activity
      within amino acids 271-900. A chimeric NS5 containing the D4MT/D4GT and the D2POL
      domains in the context of wild-type (WT) D2 RNA was constructed. RNAs synthesized
      in vitro were transfected into baby hamster kidney cells. The viral replication
      was analyzed by an indirect immunofluorescence assay to monitor NS1 expression
      and by quantitative real-time PCR. WT D2 RNA-transfected cells were NS1- positive
      by day 5, whereas the chimeric RNA-transfected cells became NS1-positive ~30 days
      post-transfection in three independent experiments. Sequence analysis covering
      the entire genome revealed the appearance of a single K74I mutation within the
      D4MT domain ~16 days post-transfection in two experiments. In the third, D290N
      mutation in the conserved NS3 Walker B motif appeared >=16 days post
      transfection. A time course study of serial passages revealed that the 30-day
      supernatant had gradually evolved to gain replication fitness. Trans
      complementation by co-expression of WT D2 NS5 accelerated viral replication of
      chimeric RNA without changing the K74I mutation. However, the MT and POL
      activities of NS5 WT D2 and the chimeric NS5 proteins with or without the K74I
      mutation are similar. Taken together, our results suggest that evolution of the
      functional interactions involving the chimeric NS5 protein encoded by the viral
      genome species is essential for gain of viral replication fitness. 

PMID- 24904062
TI  - Epigenetic modulation of intestinal cholesterol transporter Niemann-Pick C1-like
      1 (NPC1L1) gene expression by DNA methylation.
AB  - Intestinal NPC1L1 transporter is essential for cholesterol absorption and the
      maintenance of cholesterol homeostasis in the body. NPC1L1 is differentially
      expressed along the gastrointestinal tract with very low levels in the colon as
      compared with the small intestine. This study was undertaken to examine whether
      DNA methylation was responsible for segment-specific expression of NPC1L1.
      Treatment of mice with 5-azacytidine (i.p.) resulted in a significant dose
      dependent increase in NPC1L1 mRNA expression in the colon. The lack of expression
      of NPC1L1 in the normal colon was associated with high levels of methylation in
      the area flanking the 3-kb fragment upstream of the initiation site of the mouse
      NPC1L1 gene in mouse colon as analyzed by EpiTYPER(r) MassARRAY(r). The high
      level of methylation in the colon was observed in specific CpG dinucleotides and
      was significantly decreased in response to 5-azacytidine. Similar to mouse
      NPC1L1, 5-azacytidine treatment also increased the level of human NPC1L1 mRNA
      expression in the intestinal HuTu-80 cell line in a dose- and time-dependent
      manner. Silencing the expression of DNA methyltransferase DNMT1, -2, -3A, and -3B
      alone by siRNA did not affect NPC1L1 expression in HuTu-80 cells. However, the
      simultaneous attenuation of DNMT1 and -3B expression caused a significant
      increase in NPC1L1 mRNA expression as compared with control. Also, in vitro
      methylation of the human NPC1L1 promoter significantly decreased NPC1L1 promoter
      activity in human intestinal Caco2 cells. In conclusion, our data demonstrated
      for the first time that DNA methylation in the promoter region of the NPC1L1 gene
      appears to be a major mechanism underlying differential expression of NPC1L1
      along the length of the gastrointestinal tract. 

PMID- 24904064
TI  - Axl receptor tyrosine kinase expression in breast cancer.
AB  - AIMS: Triple-negative breast cancer comprises a clinically aggressive group of
      invasive carcinomas. We examined a published gene expression screen of a panel of
      breast cancer cell lines to identify a potential triple-negative breast cancer
      specific gene signature, and attempted to verify our findings by performing
      immunohistochemical analysis on tissue microarrays containing a large cohort of
      invasive breast carcinomas. METHODS: The microarray dataset for a panel of human
      breast cancer cell lines was interrogated for triple-negative breast cancer
      specific genes. Membranous immunohistochemical expression of the protein product
      of the AXL gene was assessed semiquantitatively in 569 invasive breast carcinomas
      grouped according to molecular subgroup by immunohistochemistry. RESULTS: AXL was
      significantly upregulated in triple-negative/basal B cell lines compared with
      luminal or basal A cell lines. No significant difference was observed in the
      level of immunohistochemical expression of Axl protein between triple-negative
      breast cancers and other molecular subgroups (p=0.257). Axl expression was
      significantly associated with lymphovascular invasion (LVI) in all subgroups
      combined (p=0.033), and within the luminal A (p=0.002) and triple-negative breast
      cancer subgroups (p=0.026). CONCLUSIONS: Despite preferential upregulation of AXL
      in triple-negative/basal B cell lines, analysis of Axl protein expression in a
      large series of patients' breast tumours revealed no association between Axl
      expression and triple-negative breast cancer or other subtype. The association of
      Axl expression with LVI supports previous work that implicates Axl as a promoter
      of invasiveness in breast cancer cell lines. Further studies are necessary to
      explore whether Axl expression of individual breast cancer tumours can be
      clinically useful.

PMID- 24904063
TI  - Allosteric inhibition of human immunodeficiency virus integrase: late block
      during viral replication and abnormal multimerization involving specific protein
      domains.
AB  - HIV-1 replication in the presence of antiviral agents results in evolution of
      drug-resistant variants, motivating the search for additional drug classes. Here
      we report studies of GSK1264, which was identified as a compound that disrupts
      the interaction between HIV-1 integrase (IN) and the cellular factor lens
      epithelium-derived growth factor (LEDGF)/p75. GSK1264 displayed potent antiviral
      activity and was found to bind at the site occupied by LEDGF/p75 on IN by x-ray
      crystallography. Assays of HIV replication in the presence of GSK1264 showed only
      modest inhibition of the early infection steps and little effect on integration
      targeting, which is guided by the LEDGF/p75-IN interaction. In contrast,
      inhibition of late replication steps was more potent. Particle production was
      normal, but particles showed reduced infectivity. GSK1264 promoted aggregation of
      IN and preformed LEDGF/p75-IN complexes, suggesting a mechanism of inhibition.
      LEDGF/p75 was not displaced from IN during aggregation, indicating trapping of
      LEDGF/p75 in aggregates. Aggregation assays with truncated IN variants revealed
      that a construct with catalytic and C-terminal domains of IN only formed an open
      polymer associated with efficient drug-induced aggregation. These data suggest
      that the allosteric inhibitors of IN are promising antiviral agents and provide
      new information on their mechanism of action.

PMID- 24904065
TI  - Negative Urgency Mediates the Relationship between Amygdala and Orbitofrontal
      Cortex Activation to Negative Emotional Stimuli and General Risk-Taking.
AB  - The tendency toward impulsive behavior under emotional duress (negative and
      positive urgency) predicts a wide range of maladaptive risk-taking and behavioral
      disorders. However, it remains unclear how urgency relates to limbic system
      activity as induced from emotional provocation. This study used functional
      magnetic resonance imaging to examine the relationship between brain responses to
      visual emotional stimuli and urgency traits. Twenty-seven social drinkers (mean
      age = 25.2, 14 males) viewed negative (Neg), neutral (Neu), and positive (Pos)
      images during 6 fMRI scans. Brain activation was extracted from a priori limbic
      regions previously identified in studies of emotional provocation. The right
      posterior orbitofrontal cortex (OFC) and left amygdala were activated in the
      [Neg>Neu] contrast, whereas the left posterior OFC was activated in the [Pos>Neu]
      contrast. Negative urgency was related to the right lateral OFC (r = 0.43, P =
      0.03) and the left amygdala (r = 0.39, P = 0.04) [Neg>Neu] activation. Negative
      urgency also mediated the relationship between [Neg>Neu] activation and general
      risk-taking (regression weights = 3.42 for right OFC and 2.75 for the left
      amygdala). Emotional cue-induced activation in right lateral OFC and left
      amygdala might relate to emotion-based risk-taking through negative urgency. 

PMID- 24904066
TI  - An Intracranial EEG Study of the Neural Dynamics of Musical Valence Processing.
AB  - The processing of valence is known to recruit the amygdala, orbitofrontal cortex,
      and relevant sensory areas. However, how these regions interact remains unclear.
      We recorded cortical electrical activity from 7 epileptic patients implanted with
      depth electrodes for presurgical evaluation while they listened to positively and
      negatively valenced musical chords. Time-frequency analysis suggested a specific
      role of the orbitofrontal cortex in the processing of positively valenced stimuli
      while, most importantly, Granger causality analysis revealed that the amygdala
      tends to drive both the orbitofrontal cortex and the auditory cortex in theta and
      alpha frequency bands, during the processing of valenced stimuli. Results from
      the current study show the amygdala to be a critical hub in the emotion
      processing network: specifically one that influences not only the higher order
      areas involved in the evaluation of a stimulus's emotional value but also the
      sensory cortical areas involved in the processing of its low-level acoustic
      features. 

PMID- 24904067
TI  - Parcellation of Human and Monkey Core Auditory Cortex with fMRI Pattern
      Classification and Objective Detection of Tonotopic Gradient Reversals.
AB  - Auditory cortex (AC) contains several primary-like, or "core," fields, which
      receive thalamic input and project to non-primary "belt" fields. In humans, the
      organization and layout of core and belt auditory fields are still poorly
      understood, and most auditory neuroimaging studies rely on macroanatomical
      criteria, rather than functional localization of distinct fields. A
      myeloarchitectonic method has been suggested recently for distinguishing between
      core and belt fields in humans (Dick F, Tierney AT, Lutti A, Josephs O, Sereno
      MI, Weiskopf N. 2012. In vivo functional and myeloarchitectonic mapping of human
      primary auditory areas. J Neurosci. 32:16095-16105). We propose a marker for core
      AC based directly on functional magnetic resonance imaging (fMRI) data and
      pattern classification. We show that a portion of AC in Heschl's gyrus classifies
      sound frequency more accurately than other regions in AC. Using fMRI data from
      macaques, we validate that the region where frequency classification performance
      is significantly above chance overlaps core auditory fields, predominantly A1.
      Within this region, we measure tonotopic gradients and estimate the locations of
      the human homologues of the core auditory subfields A1 and R. Our results provide
      a functional rather than anatomical localizer for core AC. We posit that inter
      individual variability in the layout of core AC might explain disagreements
      between results from previous neuroimaging and cytological studies. 

PMID- 24904068
TI  - Listen to Yourself: The Medial Prefrontal Cortex Modulates Auditory Alpha Power
      During Speech Preparation.
AB  - How do we process stimuli that stem from the external world and stimuli that are
      self-generated? In the case of voice perception it has been shown that evoked
      activity elicited by self-generated sounds is suppressed compared with the same
      sounds played-back externally. We here wanted to reveal whether neural
      excitability of the auditory cortex-putatively reflected in local alpha band
      power--is modulated already prior to speech onset, and which brain regions may
      mediate such a top-down preparatory response. In the left auditory cortex we show
      that the typical alpha suppression found when participants prepare to listen
      disappears when participants expect a self-spoken sound. This suggests an
      inhibitory adjustment of auditory cortical activity already before sound onset.
      As a second main finding we demonstrate that the medial prefrontal cortex, a
      region known for self-referential processes, mediates these condition-specific
      alpha power modulations. This provides crucial insights into how higher-order
      regions prepare the auditory cortex for the processing of self-generated sounds.
      Furthermore, the mechanism outlined could provide further explanations to self
      referential phenomena, such as "tickling yourself". Finally, it has implications
      for the so-far unsolved question of how auditory alpha power is mediated by
      higher-order regions in a more general sense.

PMID- 24904069
TI  - Electrocorticography Reveals Enhanced Visual Cortex Responses to Visual Speech.
AB  - Human speech contains both auditory and visual components, processed by their
      respective sensory cortices. We test a simple model in which task-relevant speech
      information is enhanced during cortical processing. Visual speech is most
      important when the auditory component is uninformative. Therefore, the model
      predicts that visual cortex responses should be enhanced to visual-only (V)
      speech compared with audiovisual (AV) speech. We recorded neuronal activity as
      patients perceived auditory-only (A), V, and AV speech. Visual cortex showed
      strong increases in high-gamma band power and strong decreases in alpha-band
      power to V and AV speech. Consistent with the model prediction, gamma-band
      increases and alpha-band decreases were stronger for V speech. The model predicts
      that the uninformative nature of the auditory component (not simply its absence)
      is the critical factor, a prediction we tested in a second experiment in which
      visual speech was paired with auditory white noise. As predicted, visual speech
      with auditory noise showed enhanced visual cortex responses relative to AV
      speech. An examination of the anatomical locus of the effects showed that all
      visual areas, including primary visual cortex, showed enhanced responses. Visual
      cortex responses to speech are enhanced under circumstances when visual
      information is most important for comprehension. 

PMID- 24904070
TI  - Hippocampal Wnt3a is Necessary and Sufficient for Contextual Fear Memory
      Acquisition and Consolidation.
AB  - The Wnt signaling pathway plays critical roles in development. However, to date,
      the role of Wnts in learning and memory in adults is still not well understood.
      Here, we aimed to investigate the roles and mechanisms of Wnts in hippocampal
      dependent contextual fear conditioning (CFC) memory formation in adult mice. CFC
      training induced the secretion and expression of Wnt3a and the activation of its
      downstream Wnt/Ca(2+) and Wnt/beta-catenin signaling pathways in the dorsal
      hippocampus (DH). Intrahippocampal infusion of Wnt3a antibody impaired CFC
      acquisition and consolidation, but not expression. Using the Wnt antagonist sFRP1
      or the canonical Wnt inhibitor Dkk1, we found that Wnt/Ca(2+) and Wnt/beta
      catenin signaling pathways were involved in acquisition and consolidation,
      respectively. Moreover, we found Wnt3a signaling is not only necessary but also
      sufficient for CFC memory. Intrahippocampal infusion of exogenous Wnt3a could
      enhance acquisition and consolidation of CFC. Overexpression of constitutively
      active beta-catenin in the DH could rescue the deficit in CFC memory
      consolidation, but not acquisition induced by Wnt3a antibody injection, which
      suggests beta-catenin signaling pathway acts downstream of Wnt3a to mediate CFC
      memory consolidation. Our study may help further the understanding of the precise
      regulation of Wnt3a in differential memory phases depending on divergent
      signaling pathways. 

PMID- 24904072
TI  - Environmental Enrichment Duration Differentially Affects Behavior and
      Neuroplasticity in Adult Mice.
AB  - Environmental enrichment is a powerful way to stimulate brain and behavioral
      plasticity. However the required exposure duration to reach such changes has not
      been substantially analyzed. We aimed to assess the time-course of appearance of
      the beneficial effects of enriched environment. Thus, different behavioral tests
      and neurobiological parameters (such as neurogenesis, brain monoamines levels,
      and stress-related hormones) were concomitantly realized after different
      durations of enriched environment (24 h, 1, 3, or 5 weeks). While short
      enrichment exposure (24 h) was sufficient to improve object recognition memory
      performances, a 3-week exposure was required to improve aversive stimulus-based
      memory performances and to reduce anxiety-like behavior; effects that were not
      observed with longer duration. The onset of behavioral changes after a 3-week
      exposure might be supported by higher serotonin levels in the frontal cortex, but
      seems independent of neurogenesis phenomenon. Additionally, the benefit of 3-week
      exposure on memory was not observed 3 weeks after cessation of enrichment. Thus,
      the 3-week exposure appears as an optimal duration in order to induce the most
      significant behavioral effects and to assess the underlying mechanisms.
      Altogether, these results suggest that the duration of exposure is a keystone of
      the beneficial behavioral and neurobiological effects of environmental
      enrichment. 

PMID- 24904073
TI  - Behavioral Regulation and the Modulation of Information Coding in the Lateral
      Prefrontal and Cingulate Cortex.
AB  - To explain the high level of flexibility in primate decision-making, theoretical
      models often invoke reinforcement-based mechanisms, performance monitoring
      functions, and core neural features within frontal cortical regions. However, the
      underlying biological mechanisms remain unknown. In recent models, part of the
      regulation of behavioral control is based on meta-learning principles, for
      example, driving exploratory actions by varying a meta-parameter, the inverse
      temperature, which regulates the contrast between competing action probabilities.
      Here we investigate how complementary processes between lateral prefrontal cortex
      (LPFC) and dorsal anterior cingulate cortex (dACC) implement decision regulation
      during exploratory and exploitative behaviors. Model-based analyses of unit
      activity recorded in these 2 areas in monkeys first revealed that adaptation of
      the decision function is reflected in a covariation between LPFC neural activity
      and the control level estimated from the animal's behavior. Second, dACC more
      prominently encoded a reflection of outcome uncertainty useful for control
      regulation based on task monitoring. Model-based analyses also revealed higher
      information integration before feedback in LPFC, and after feedback in dACC.
      Overall the data support a role of dACC in integrating reinforcement-based
      information to regulate decision functions in LPFC. Our results thus provide
      biological evidence on how prefrontal cortical subregions may cooperate to
      regulate decision-making. 

PMID- 24904071
TI  - Functional Maturation of GABA Synapses During Postnatal Development of the Monkey
      Dorsolateral Prefrontal Cortex.
AB  - Development of inhibition onto pyramidal cells may be crucial for the emergence
      of cortical network activity, including gamma oscillations. In primate
      dorsolateral prefrontal cortex (DLPFC), inhibitory synaptogenesis starts in utero
      and inhibitory synapse density reaches adult levels before birth. However, in
      DLPFC, the expression levels of gamma-aminobutyric acid (GABA) synapse-related
      gene products changes markedly during development until young adult age,
      suggesting a highly protracted maturation of GABA synapse function. Therefore, we
      examined the development of GABA synapses by recording GABAAR-mediated inhibitory
      postsynaptic currents (GABAAR-IPSCs) from pyramidal cells in the DLPFC of
      neonatal, prepubertal, peripubertal, and adult macaque monkeys. We found that the
      decay of GABAAR-IPSCs, possibly including those from parvalbumin-positive GABA
      neurons, shortened by prepubertal age, while their amplitude increased until the
      peripubertal period. Interestingly, both GABAAR-mediated quantal response size,
      estimated by miniature GABAAR-IPSCs, and the density of GABAAR synaptic
      appositions, measured with immunofluorescence microscopy, were stable with age.
      Simulations in a computational model network with constant GABA synapse density
      showed that the developmental changes in GABAAR-IPSC properties had a significant
      impact on oscillatory activity and predicted that, whereas DLPFC circuits can
      generate gamma frequency oscillations by prepubertal age, mature levels of gamma
      band power are attained at late stages of development. 

PMID- 24904074
TI  - Local and Global Correlations between Neurons in the Middle Temporal Area of
      Primate Visual Cortex.
AB  - In humans and other primates, the analysis of visual motion includes populations
      of neurons in the middle-temporal (MT) area of visual cortex. Motion analysis
      will be constrained by the structure of neural correlations in these populations.
      Here, we use multi-electrode arrays to measure correlations in anesthetized
      marmoset, a New World monkey where area MT lies exposed on the cortical surface.
      We measured correlations in the spike count between pairs of neurons and within
      populations of neurons, for moving dot fields and moving gratings. Correlations
      were weaker in area MT than in area V1. The magnitude of correlations in area MT
      diminished with distance between receptive fields, and difference in preferred
      direction. Correlations during presentation of moving gratings were stronger than
      those during presentation of moving dot fields, extended further across cortex,
      and were less dependent on the functional properties of neurons. Analysis of the
      timescales of correlation suggests presence of 2 mechanisms. A local mechanism,
      associated with near-synchronous spiking activity, is strongest in nearby neurons
      with similar direction preference and is independent of visual stimulus. A global
      mechanism, operating over larger spatial scales and longer timescales, is
      independent of direction preference and is modulated by the type of visual
      stimulus presented. 

PMID- 24904075
TI  - The Persistence of Experience: Prior Attentional and Emotional State Affects
      Network Functioning in a Target Detection Task.
AB  - Efficient, adaptive behavior relies on the ability to flexibly move between
      internally focused (IF) and externally focused (EF) attentional states. Despite
      evidence that IF cognitive processes such as event imagination comprise a
      significant amount of awake cognition, the consequences of internal absorption on
      the subsequent recruitment of brain networks during EF tasks are unknown. The
      present functional magnetic resonance imaging (fMRI) study employed a novel
      attentional state switching task. Subjects imagined positive and negative events
      (IF task) or performed a working memory task (EF task) before switching to a
      target detection (TD) task also requiring attention to external information,
      allowing for the investigation of neural functioning during external attention
      based on prior attentional state. There was a robust increase of activity in
      frontal, parietal, and temporal regions during TD when subjects were previously
      performing the EF compared with IF task, an effect that was most pronounced
      following negative IF. Additionally, dorsolateral prefrontal cortex was less
      negatively coupled with ventromedial prefrontal and posterior cingulate cortices
      during TD following IF compared with EF. These findings reveal the striking
      consequences for brain activity following immersion in an IF attentional state,
      which have strong implications for psychiatric disorders characterized by
      excessive internal focus. 

PMID- 24904076
TI  - Conversational Interaction in the Scanner: Mentalizing during Language Processing
      as Revealed by MEG.
AB  - Humans are especially good at taking another's perspective-representing what
      others might be thinking or experiencing. This "mentalizing" capacity is apparent
      in everyday human interactions and conversations. We investigated its neural
      basis using magnetoencephalography. We focused on whether mentalizing was engaged
      spontaneously and routinely to understand an utterance's meaning or largely on
      demand, to restore "common ground" when expectations were violated. Participants
      conversed with 1 of 2 confederate speakers and established tacit agreements about
      objects' names. In a subsequent "test" phase, some of these agreements were
      violated by either the same or a different speaker. Our analysis of the neural
      processing of test phase utterances revealed recruitment of neural circuits
      associated with language (temporal cortex), episodic memory (e.g., medial
      temporal lobe), and mentalizing (temporo-parietal junction and ventromedial
      prefrontal cortex). Theta oscillations (3-7 Hz) were modulated most prominently,
      and we observed phase coupling between functionally distinct neural circuits. The
      episodic memory and language circuits were recruited in anticipation of upcoming
      referring expressions, suggesting that context-sensitive predictions were
      spontaneously generated. In contrast, the mentalizing areas were recruited on
      demand, as a means for detecting and resolving perceived pragmatic anomalies,
      with little evidence they were activated to make partner-specific predictions
      about upcoming linguistic utterances. 

PMID- 24904077
TI  - Enteropathogenic Escherichia coli dynamically regulates EGFR signaling in
      intestinal epithelial cells.
AB  - The diarrheagenic pathogen enteropathogenic Escherichia coli (EPEC) dynamically
      modulates the survival of infected host intestinal epithelial cells. In the
      initial stages of infection, several prosurvival signaling events are activated
      in host cells. These include the phosphorylation of epidermal growth factor
      receptor (EGFR) and the consequent activation of the phosphatidylinositol-3
      kinase/Akt pathway. While studying this pathway in infected epithelial cells, we
      observed EGFR depletion at later stages of infection, followed subsequently by a
      decrease in phospho-EGFR. EGFR loss was not dependent on receptor
      phosphorylation, or on canonical proteasome- and lysosome-dependent processes.
      Although a type III secretion mutant (DeltaescN) stimulated EGFR phosphorylation,
      it failed to induce receptor degradation. To identify the specific EPEC effector
      molecule(s) that influenced EGFR stability, epithelial cells infected with
      isogenic mutant EPEC strains were examined. An EPEC DeltaespF strain failed to
      induce EGFR degradation, whereas EPEC DeltaespZ accentuated receptor loss in
      infected cells. Given the known and contrasting effects of EspF and EspZ on
      caspase activation, and the known role of proteases in cleaving EGFR, we explored
      the effect of caspase inhibitors on infection-dependent EGFR loss. The pan
      caspase inhibitor Q-VD-OPh blocked EPEC-induced EGFR cleavage in a dose-dependent
      manner. Taken together, our data suggest that EPEC EspF stimulates caspase
      dependent EGFR cleavage and loss, whereas EspZ inhibits this process. Whereas
      EGFR phosphorylation contributes to the survival of host cells early in
      infection, EspF-driven caspase activation and consequent EGFR loss likely induce
      a precipitous increase in host cell death later in the infectious process. 

PMID- 24904078
TI  - Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated,
      lipopolysaccharide-sensitive carrier-mediated process.
AB  - Biotin is essential for the normal function of pancreatic beta cells. These cells
      obtain biotin from their surroundings via transport across their cell membrane.
      Little is known about the uptake mechanism involved, how it is regulated, and how
      it is affected by internal and external factors. We addressed these issues using
      the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human
      primary pancreatic beta cells as models. The results showed biotin uptake by
      pancreatic beta-TC-6 cells occurs via a Na(+)-dependent, carrier-mediated
      process, that is sensitive to desthiobiotin, as well as to pantothenic acid and
      lipoate; the process is also saturable as a function of concentration (apparent
      Km = 22.24 +/- 5.5 MUM). These cells express the sodium-dependent multivitamin
      transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a
      sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human
      primary pancreatic islets is Na(+)-dependent and carrier-mediated, and both cell
      types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also
      adaptively regulated (via transcriptional mechanism) by extracellular substrate
      level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial
      lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition
      is mediated via a Toll-Like receptor 4-mediated process and involves a decrease
      in membrane expression of SMVT. These findings show, for the first time, that
      pancreatic beta cells/islets take up biotin via a specific and regulated carrier
      mediated process, and that the process is sensitive to the effect of LPS. 

PMID- 24904079
TI  - Cytotoxicity and metabolic stress induced by acetaldehyde in human intestinal
      LS174T goblet-like cells.
AB  - There is compelling evidence indicating that ethanol and its oxidative metabolite
      acetaldehyde can disrupt intestinal barrier function. Apart from the tight
      junctions, mucins secreted by goblet cells provide an effective barrier. Ethanol
      has been shown to induce goblet cell injury associated with alterations in mucin
      glycosylation. However, effects of its most injurious metabolite acetaldehyde
      remain largely unknown. This study aimed to assess short-term effects of
      acetaldehyde (0, 25, 50, 75, 100 MUM) on functional characteristics of intestinal
      goblet-like cells (LS174T). Oxidative stress, mitochondrial function, ATP, and
      intramitochondrial calcium (Ca(2+)) were assessed by dichlorofluorescein,
      methyltetrazolium, and bioluminescence, MitoTracker green and rhod-2 double
      labeling. Membrane integrity and apoptosis were evaluated by measuring lactate
      dehydrogenase (LDH), caspase 3/7, and cleavage of cytokeratin 18 (CK18).
      Expression of mucin 2 (MUC2) was determined by cell-based ELISA. Acetaldehyde
      significantly increased reactive oxygen species generation and decreased
      mitochondrial function compared with negative controls (P < 0.05). In addition,
      acetaldehyde dose-dependently decreased ATP levels and induced intramitochondrial
      Ca(2+) accumulation compared with negative controls (P < 0.05). Furthermore,
      acetaldehyde induced LDH release and increased caspase3/7 activity and percentage
      of cells expressing cleaved CK18 and increased MUC2 protein expression compared
      with negative controls (P < 0.0001). ATP depletion and LDH release could be
      largely prevented by the antioxidant N-acetylcysteine, suggesting a pivotal role
      for oxidative stress. Our data demonstrate that acetaldehyde has distinct oxidant
      dependent metabolic and cytotoxic effects on LS174T cells that can lead to
      induction of cellular apoptosis. These effects may contribute to acetaldehyde
      induced intestinal barrier dysfunction and subsequently to liver injury. 

PMID- 24904081
TI  - Odor coding in a disease-transmitting herbivorous insect, the Asian citrus
      psyllid.
AB  - Olfactory systems discriminate odorants very efficiently and herbivorous insects
      use them to find hosts in confounding and complex odor landscapes. The Asian
      citrus psyllid (ACP), Diaphorina citri, feeds on citrus flush and transmits
      Candidatus Liberibacter that causes citrus greening disease globally. Here, we
      perform a systematic analysis of odor detection in the ACP antenna using single
      unit electrophysiology of rhinarial plate sensilla to a large panel of odorants
      from plants. We identify neurons that respond strongly to odorants found in the
      host citrus plants. Comparisons with the generalist yeast-feeding Drosophila
      melanogaster and specialist anthropophilic Anopheles gambiae reveal differences
      in odor-coding strategies for the citrus-seeking ACP. These findings provide a
      foundation for understanding host-odor coding in herbivorous insects. 

PMID- 24904080
TI  - Argininosuccinate lyase in enterocytes protects from development of necrotizing
      enterocolitis.
AB  - Necrotizing enterocolitis (NEC), the most common neonatal gastrointestinal
      emergency, results in significant mortality and morbidity, yet its pathogenesis
      remains unclear. Argininosuccinate lyase (ASL) is the only enzyme in mammals that
      is capable of synthesizing arginine. Arginine has several homeostatic roles in
      the gut and its deficiency has been associated with NEC. Because enterocytes are
      the primary sites of arginine synthesis in neonatal mammals, we evaluated the
      consequences of disruption of arginine synthesis in the enterocytes on the
      pathogenesis of NEC. We devised a novel approach to study the role of enterocyte
      derived ASL in NEC by generating and characterizing a mouse model with enterocyte
      specific deletion of Asl (Asl(flox/flox); VillinCre(tg/+), or CKO). We
      hypothesized that the presence of ASL in a cell-specific manner in the
      enterocytes is protective in the pathogenesis of NEC. Loss of ASL in enterocytes
      resulted in an increased incidence of NEC that was associated with a
      proinflammatory state and increased enterocyte apoptosis. Knockdown of ASL in
      intestinal epithelial cell lines resulted in decreased migration in response to
      lipopolysaccharide. Our results show that enterocyte-derived ASL has a protective
      role in NEC. 

PMID- 24904082
TI  - A novel atypical hemolytic uremic syndrome-associated hybrid CFHR1/CFH gene
      encoding a fusion protein that antagonizes factor H-dependent complement
      regulation.
AB  - Genomic aberrations affecting the genes encoding factor H (FH) and the five FH
      related proteins (FHRs) have been described in patients with atypical hemolytic
      uremic syndrome (aHUS), a rare condition characterized by microangiopathic
      hemolytic anemia, thrombocytopenia, and ARF. These genomic rearrangements occur
      through nonallelic homologous recombinations caused by the presence of repeated
      homologous sequences in CFH and CFHR1-R5 genes. In this study, we found
      heterozygous genomic rearrangements among CFH and CFHR genes in 4.5% of patients
      with aHUS. CFH/CFHR rearrangements were associated with poor clinical prognosis
      and high risk of post-transplant recurrence. Five patients carried known
      CFH/CFHR1 genes, but we found a duplication leading to a novel CFHR1/CFH hybrid
      gene in a family with two affected subjects. The resulting fusion protein
      contains the first four short consensus repeats of FHR1 and the terminal short
      consensus repeat 20 of FH. In an FH-dependent hemolysis assay, we showed that the
      hybrid protein causes sheep erythrocyte lysis. Functional analysis of the FHR1
      fraction purified from serum of heterozygous carriers of the CFHR1/CFH hybrid
      gene indicated that the FHR1/FH hybrid protein acts as a competitive antagonist
      of FH. Furthermore, sera from carriers of the hybrid CFHR1/CFH gene induced more
      C5b-9 deposition on endothelial cells than control serum. These results suggest
      that this novel genomic hybrid mediates disease pathogenesis through
      dysregulation of complement at the endothelial cell surface. We recommend that
      genetic screening of aHUS includes analysis of CFH and CFHR rearrangements,
      particularly before a kidney transplant. 

PMID- 24904083
TI  - Klotho gene deficiency causes salt-sensitive hypertension via monocyte
      chemotactic protein-1/CC chemokine receptor 2-mediated inflammation.
AB  - Klotho (KL) is a newly discovered aging suppressor gene. In mice, the KL gene
      extends the lifespan when overexpressed and shortens the lifespan when disrupted.
      This study investigated if KL deficiency affects BP and salt sensitivity using KL
      mutant heterozygous (+/-) mice and wild-type (WT) mice (9 weeks of age, 16 mice
      per group). Notably, systolic BP in KL(+/-) mice began to increase at the age of
      15 weeks, reached a peak level at the age of 17 weeks, and remained elevated
      thereafter, whereas systolic BP remained consistent in WT mice. High salt (HS)
      intake further increased BP in KL(+/-) mice but did not affect BP in WT mice.
      Blockade of CC chemokine receptor 2 (CCR2), involved in monocyte chemotaxis, by a
      specific CCR2 antagonist (INCB3284) abolished the HS-induced increase in BP in
      KL(+/-) mice. Furthermore, HS loading substantially increased the expression of
      monocyte chemotactic protein-1 and the infiltration of macrophages and T cells in
      kidneys in KL(+/-) mice, and treatment with INCB3284 abolished these effects.
      Treatment of KL(+/-) mice with INCB3284 also attenuated the increased renal
      expressions of serum glucocorticoid-regulated kinase 1, thiazide-sensitive NaCl
      cotransporter, and ATP synthase beta along with the renal structural damage and
      functional impairment induced by HS loading. In conclusion, KL deficiency caused
      salt-sensitive hypertension and renal damage by CCR2-mediated inflammation. 

PMID- 24904085
TI  - Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury
      and predicts progression to ESRD in type I diabetes.
AB  - Currently, no blood biomarker that specifically indicates injury to the proximal
      tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is
      highly upregulated in proximal tubular cells following kidney injury. The
      ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of
      kidney injury. We report that shed KIM-1 also serves as a blood biomarker of
      kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats,
      and humans were developed and validated in the current study. Plasma KIM-1 levels
      increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as
      early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7)
      in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In
      humans, plasma KIM-1 levels were higher in patients with AKI than in healthy
      controls or post-cardiac surgery patients without AKI (area under the curve,
      0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels
      increased within 2 days after surgery only in patients who developed AKI
      (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous
      etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum
      KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD
      during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to
      creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood
      biomarker that specifically reflects acute and chronic kidney injury. 

PMID- 24904084
TI  - Adam10 mediates the choice between principal cells and intercalated cells in the
      kidney.
AB  - A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM
      family of cell membrane-anchored proteins, has been linked to the regulation of
      the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear
      what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10
      deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary
      concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10
      deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2)(+)
      principal cells (PCs) in the collecting ducts that was accompanied by a
      proportional increase in the percentage of intercalated cells (ICs). This
      increase was more prominent in type A ICs than in type B ICs. Foxi1, a
      transcription factor important for the differentiation of ICs, was upregulated in
      the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant
      collecting duct epithelium and the similar reduction of PC/IC ratios in the
      collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a
      key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling
      pathways, suggest that Adam10 regulates cell fate determination through the
      activation of Notch signaling, probably through the regulation of Foxi1
      expression. However, phenotypic differences between the Adam10 mutants, the Mib1
      mutants, and the Foxi1 mutants suggest that the functions of Adam10 in
      determining the fate of collecting duct cells are more complex than those of a
      simple upstream factor in a linear pathway involving Notch and Foxi1. 

PMID- 24904086
TI  - Improved glycemic control and risk of ESRD in patients with type 1 diabetes and
      proteinuria.
AB  - Most patients with type 1 diabetes (T1D) and proteinuria have poor glycemic
      control and a high risk of ESRD. We investigated whether long-term improvement of
      glycemic control reduces risk of ESRD in a prospective 7- to 15-year follow-up
      observation of 349 patients with CKD stages 1-3 enrolled in the Joslin
      Proteinuria Cohort of adults with T1D. All patients developed proteinuria between
      1990 and 2004 and were followed until 2011 to ascertain onset of ESRD and deaths
      unrelated to ESRD. Furthermore, we analyzed data from 279 patients with >=3 years
      of clinic follow-up available to assess the level of glycemic control after
      enrollment. Average HbA1c during the 5 years before study enrollment
      (prebaseline) was compared with HbA1c (postbaseline) averaged during the first
      half of follow-up (median, 5.1 years). Median prebaseline HbA1c was 9.3%,
      decreasing to 8.7% postbaseline. Cumulative risk of ESRD after 15 years was
      significantly lower for patients whose HbA1c decreased than for those whose HbA1c
      increased or remained poor (29% versus 42%; P<0.001). The difference between
      these groups was not visible at 5 years of follow-up but became visible at 10 and
      15 years of follow-up. In multivariate Cox regression analysis of ESRD risk, the
      hazard ratio corresponding to a 1-percentage point improvement in postbaseline
      HbA1c was 0.76 (95% confidence interval, 0.63 to 0.91; P=0.003). In conclusion,
      results of this study suggest that long-term sustained improvement in HbA1c
      decelerates eGFR loss and delays the onset of ESRD in patients with T1D and
      proteinuria.

PMID- 24904087
TI  - Collecting duct-derived cells display mesenchymal stem cell properties and retain
      selective in vitro and in vivo epithelial capacity.
AB  - We previously described a mesenchymal stem cell (MSC)-like population within the
      adult mouse kidney that displays long-term colony-forming efficiency,
      clonogenicity, immunosuppression, and panmesodermal potential. Although
      phenotypically similar to bone marrow (BM)-MSCs, kidney MSC-like cells display a
      distinct expression profile. FACS sorting from Hoxb7/enhanced green fluorescent
      protein (GFP) mice identified the collecting duct as a source of kidney MSC-like
      cells, with these cells undergoing an epithelial-to-mesenchymal transition to
      form clonogenic, long-term, self-renewing MSC-like cells. Notably, after
      extensive passage, kidney MSC-like cells selectively integrated into the
      aquaporin 2-positive medullary collecting duct when microinjected into the
      kidneys of neonatal mice. No epithelial integration was observed after injection
      of BM-MSCs. Indeed, kidney MSC-like cells retained a capacity to form epithelial
      structures in vitro and in vivo, and conditioned media from these cells supported
      epithelial repair in vitro. To investigate the origin of kidney MSC-like cells,
      we further examined Hoxb7(+) fractions within the kidney across postnatal
      development, identifying a neonatal interstitial GFP(lo) (Hoxb7(lo)) population
      displaying an expression profile intermediate between epithelium and
      interstitium. Temporal analyses with Wnt4(GCE/+):R26(tdTomato/+) mice revealed
      evidence for the intercalation of a Wnt4-expressing interstitial population into
      the neonatal collecting duct, suggesting that such intercalation may represent a
      normal developmental mechanism giving rise to a distinct collecting duct
      subpopulation. These results extend previous observations of papillary stem cell
      activity and collecting duct plasticity and imply a role for such cells in
      collecting duct formation and, possibly, repair. 

PMID- 24904088
TI  - Loss of the podocyte-expressed transcription factor Tcf21/Pod1 results in
      podocyte differentiation defects and FSGS.
AB  - Podocytes are terminally differentiated cells with an elaborate cytoskeleton and
      are critical components of the glomerular barrier. We identified a bHLH
      transcription factor, Tcf21, that is highly expressed in developing and mature
      podocytes. Because conventional Tcf21 knockout mice die in the perinatal period
      with major cardiopulmonary defects, we generated a conditional Tcf21 knockout
      mouse to explore the role of this transcription factor in podocytes in vivo.
      Tcf21 was deleted from podocytes and podocyte progenitors using podocin-cre
      (podTcf21) and wnt4-cre (wnt4creTcf21) driver strains, respectively. Loss of
      Tcf21 from capillary-loop stage podocytes (podTcf21) results in simplified
      glomeruli with a decreased number of endothelial and mesangial cells. By 5 weeks
      of age, 40% of podTcf21 mice develop massive proteinuria and lesions similar to
      FSGS. Notably, the remaining 60% of mice do not develop proteinuria even when
      aged to 8 months. By contrast, earlier deletion of Tcf21 from podocyte precursors
      (wnt4creTcf21) results in a profound developmental arrest of podocyte
      differentiation and renal failure in 100% of mice during the perinatal period.
      Taken together, our results demonstrate a critical role for Tcf21 in the
      differentiation and maintenance of podocytes. Identification of direct targets of
      this transcription factor may provide new therapeutic avenues for proteinuric
      renal disease, including FSGS. 

PMID- 24904090
TI  - Recombination signal binding protein for Ig-kappaJ region regulates
      juxtaglomerular cell phenotype by activating the myo-endocrine program and
      suppressing ectopic gene expression.
AB  - Recombination signal binding protein for Ig-kappaJ region (RBP-J), the major
      downstream effector of Notch signaling, is necessary to maintain the number of
      renin-positive juxtaglomerular cells and the plasticity of arteriolar smooth
      muscle cells to re-express renin when homeostasis is threatened. We hypothesized
      that RBP-J controls a repertoire of genes that defines the phenotype of the renin
      cell. Mice bearing a bacterial artificial chromosome reporter with a mutated RBP
      J binding site in the renin promoter had markedly reduced reporter expression at
      the basal state and in response to a homeostatic challenge. Mice with conditional
      deletion of RBP-J in renin cells had decreased expression of endocrine (renin and
      Akr1b7) and smooth muscle (Acta2, Myh11, Cnn1, and Smtn) genes and regulators of
      smooth muscle expression (miR-145, SRF, Nfatc4, and Crip1). To determine whether
      RBP-J deletion decreased the endowment of renin cells, we traced the fate of
      these cells in RBP-J conditional deletion mice. Notably, the lineage staining
      patterns in mutant and control kidneys were identical, although mutant kidneys
      had fewer or no renin-expressing cells in the juxtaglomerular apparatus.
      Microarray analysis of mutant arterioles revealed upregulation of genes usually
      expressed in hematopoietic cells. Thus, these results suggest that RBP-J
      maintains the identity of the renin cell by not only activating genes
      characteristic of the myo-endocrine phenotype but also, preventing ectopic gene
      expression and adoption of an aberrant phenotype, which could have severe
      consequences for the control of homeostasis. 

PMID- 24904089
TI  - CXCL5 drives neutrophil recruitment in TH17-mediated GN.
AB  - Neutrophil trafficking to sites of inflammation is essential for the defense
      against bacterial and fungal infections, but also contributes to tissue damage in
      TH17-mediated autoimmunity. This process is regulated by chemokines, which often
      show an overlapping expression pattern and function in pathogen- and autoimmune
      induced inflammatory reactions. Using a murine model of crescentic GN, we show
      that the pathogenic TH17/IL-17 immune response induces chemokine (C-X-C motif)
      ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive
      neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was
      dispensable for neutrophil recruitment and effective bacterial clearance in a
      murine model of acute bacterial pyelonephritis. In line with these findings,
      CXCL5 expression was highly upregulated in the kidneys of patients with ANCA
      associated crescentic GN as opposed to patients with acute bacterial
      pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic
      target for the restriction of pathogenic neutrophil infiltration in TH17-mediated
      autoimmune diseases while leaving intact the neutrophil function in protective
      immunity against invading pathogens. 

PMID- 24904091
TI  - Renin lineage cells repopulate the glomerular mesangium after injury.
AB  - Mesangial cell injury has a major role in many CKDs. Because renin-positive
      precursor cells give rise to mesangial cells during nephrogenesis, this study
      tested the hypothesis that the same phenomenon contributes to glomerular
      regeneration after murine experimental mesangial injury. Mesangiolysis was
      induced by administration of an anti-mesangial cell serum in combination with
      LPS. In enhanced green fluorescent protein-reporter mice with constitutively
      labeled renin lineage cells, the size of the enhanced green fluorescent protein
      positive area in the glomerular tufts increased after mesangial injury.
      Furthermore, we generated a novel Tet-on inducible triple-transgenic LacZ
      reporter line that allowed selective labeling of renin cells along renal afferent
      arterioles of adult mice. Although no intraglomerular LacZ expression was
      detected in healthy mice, about two-thirds of the glomerular tufts became LacZ
      positive during the regenerative phase after severe mesangial injury.
      Intraglomerular renin descendant LacZ-expressing cells colocalized with mesangial
      cell markers alpha8-integrin and PDGF receptor-beta but not with endothelial,
      podocyte, or parietal epithelial cell markers. In contrast with LacZ-positive
      cells in the afferent arterioles, LacZ-positive cells in the glomerular tuft did
      not express renin. These data demonstrate that extraglomerular renin lineage
      cells represent a major source of repopulating cells for reconstitution of the
      intraglomerular mesangium after injury. 

PMID- 24904093
TI  - The ultra-performance liquid chromatography determination of domperidone and its
      process-related impurities.
AB  - A rapid ultra-performance liquid chromatography (UPLC) method for the
      determination of domperidone in the presence of its process impurities and
      droperidol was developed and validated. The rapid chromatographic separation was
      achieved using a sub 2 um Hypersil Zorbax eXtra Densely Bonded C18 column (30 *
      4.6 mm, i.d., 1.8 um). A gradient mobile phase consisting of Solvent A: 0.06 M
      ammonium acetate and Solvent B: methanol, with a flow rate of 1 mL/min was
      employed. The column temperature was set at 40 degrees C, and the diode-array
      detector was set at 280 nm. An injection volume of 3 uL was used. The currently
      utilized European Pharmacopeia (Eur. Pharm.) method employed by Janssen
      Pharmaceuticals Ltd was run on a Hypersil Base-Deactivated Silica C18 column (100
      * 4.6 mm, i.d., 3 um) with a run time of 12.5 min. The developed UPLC method,
      with a run time of 7.5 min was determined to be accurate, precise, specific,
      robust and highly sensitive according to the International Conference on
      Harmonization guidelines. The method herein demonstrated a reduction in analysis
      time of 40%, allowing for a much higher sample throughput. A solvent consumption
      decrease of over 58% was also observed, which results in a dramatic reduction in
      running costs for Janssen Pharmaceuticals Ltd. 

PMID- 24904092
TI  - Imaging classification of autosomal dominant polycystic kidney disease: a simple
      model for selecting patients for clinical trials.
AB  - The rate of renal disease progression varies widely among patients with autosomal
      dominant polycystic kidney disease (ADPKD), necessitating optimal patient
      selection for enrollment into clinical trials. Patients from the Mayo Clinic
      Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic
      resonance images and three or more eGFR measurements over >=6 months were
      classified radiologically as typical (n=538) or atypical (n=52). Total kidney
      volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe).
      Typical patients were randomly partitioned into development and internal
      validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges
      for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of
      PKD (CRISP) participants (n=173) were used for external validation. TKVe
      correlated strongly with TKVs, without systematic underestimation or
      overestimation. A longitudinal mixed regression model to predict eGFR decline
      showed that log2HtTKV and age significantly interacted with time in typical
      patients, but not in atypical patients. When 1A-1E classifications were used
      instead of log2HtTKV, eGFR slopes were significantly different among subclasses
      and, except for 1A, different from those in healthy kidney donors. The equation
      derived from the development set predicted eGFR in both validation sets. The
      frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in
      the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort.
      Class and subclass designations were stable. An easily applied classification of
      ADPKD based on HtTKV and age should optimize patient selection for enrollment
      into clinical trials and for treatment when one becomes available. 

PMID- 24904094
TI  - Worming along in amyloid cardiotoxicity.

PMID- 24904095
TI  - PDGFRB disease: right diagnosis to prolong survival.

PMID- 24904096
TI  - AML drug resistance: c-Myc comes into play.

PMID- 24904097
TI  - Socioeconomic disparities in lymphoma.

PMID- 24904098
TI  - Is glutamine depletion needed in ALL disease?

PMID- 24904099
TI  - CLL cells under flow.

PMID- 24904100
TI  - Liver not making hepcidin? Hemochromatosis!

PMID- 24904101
TI  - Me or not me? The danger of spontaneity.

PMID- 24904102
TI  - The donor's dilemma.

PMID- 24904103
TI  - The PRDX2 gene is transcriptionally silenced and de novo methylated in Hodgkin
      and Reed-Sternberg cells of classical Hodgkin lymphoma.

PMID- 24904104
TI  - Phenotypically aberrant clonal T cells in the lungs of patients with type II
      refractory celiac disease.

PMID- 24904105
TI  - ETV6 and signaling gene mutations are associated with secondary transformation of
      myelodysplastic syndromes to chronic myelomonocytic leukemia.

PMID- 24904106
TI  - CALR mutations in patients with essential thrombocythemia diagnosed in childhood
      and adolescence.

PMID- 24904107
TI  - Prospective detection of chikungunya virus in blood donors, Caribbean 2014.

PMID- 24904108
TI  - Electrodiagnosis of GBS subtypes by a single study: not yet the squaring of the
      circle.

PMID- 24904110
TI  - Performance assessment of a preclinical PET scanner with pinhole collimation by
      comparison to a coincidence-based small-animal PET scanner.
AB  - PET imaging of rodents is increasingly used in preclinical research, but its
      utility is limited by spatial resolution and signal-to-noise ratio of the images.
      A recently developed preclinical PET system uses a clustered-pinhole collimator,
      enabling high-resolution, simultaneous imaging of PET and SPECT tracers. Pinhole
      collimation strongly departs from traditional electronic collimation achieved via
      coincidence detection in PET. We investigated the potential of such a design by
      direct comparison to a traditional PET scanner. METHODS: Two small-animal PET
      scanners, 1 with electronic collimation and 1 with physical collimation using
      clustered pinholes, were used to acquire data from Jaszczak (hot rod) and uniform
      phantoms. Mouse brain imaging using (18)F-FDG PET was performed on each system
      and compared with quantitative ex vivo autoradiography as a gold standard. Bone
      imaging using (18)F-NaF allowed comparison of imaging in the mouse body. Images
      were visually and quantitatively compared using measures of contrast and noise.
      RESULTS: Pinhole PET resolved the smallest rods (diameter, 0.85 mm) in the
      Jaszczak phantom, whereas the coincidence system resolved 1.1-mm-diameter rods.
      Contrast-to-noise ratios were better for pinhole PET when imaging small rods
      (<1.1 mm) for a wide range of activity levels, but this reversed for larger rods.
      Image uniformity on the coincidence system (<3%) was superior to that on the
      pinhole system (5%). The high (18)F-FDG uptake in the striatum of the mouse brain
      was fully resolved using the pinhole system, with contrast to nearby regions
      equaling that from autoradiography; a lower contrast was found using the
      coincidence PET system. For short-duration images (low-count), the coincidence
      system was superior. CONCLUSION: In the cases for which small regions need to be
      resolved in scans with reasonably high activity or reasonably long scan times, a
      first-generation clustered-pinhole system can provide image quality in terms of
      resolution, contrast, and the contrast-to-noise ratio superior to a traditional
      PET system.

PMID- 24904111
TI  - A hepatic dose-toxicity model opening the way toward individualized
      radioembolization planning.
AB  - The 50% normal-tissue complication probability (NTCP) after lobar irradiation of
      the liver results in highly variable biologic effective doses depending on the
      modality used: a biologic effective dose for 50% (BED50) of 115, 93, and 250 Gy
      for external-beam radiotherapy, resin microsphere radioembolization, and glass
      microsphere radioembolization, respectively. This misunderstood property has made
      it difficult to predict the maximal tolerable dose as a function of microsphere
      activity and targeted liver volume. The evolution toward more selective
      catheterization techniques, resulting in more variable targeted volumes, makes it
      urgent to solve this issue. METHODS: We computed by Monte Carlo simulations the
      microsphere distribution in the portal triads based on microsphere transport
      dynamics through a synthetically grown hepatic arterial tree. Afterward, the
      microscale dose distribution was computed using a dose deposition kernel. We
      showed that the equivalent uniform dose cannot handle microscale dosimetry and
      fails to solve the discordance between the BED50 values. Consequently, we
      developed a new radiobiologic model to compute the liver NTCP from the microscale
      dose distribution. RESULTS: The new model explains all the observed BED50 values
      and provides a way to compute the hepatic dose-toxicity relationship as a
      function of microsphere activity and targeted liver volume. The NTCP obtained is
      in agreement with the data reported from clinical radioembolization studies.
      CONCLUSION: The results should encourage interventional radiologists to fine-tune
      the delivered dose to the liver as a function of the targeted volume. The present
      model could be used as the backbone of the treatment planning, allowing
      optimization of the absorbed dose to the tumors.

PMID- 24904112
TI  - In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with
      (18)F-PBR111 PET.
AB  - PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of
      patients with multiple sclerosis (MS) primarily reflects activated microglia and
      macrophages. We previously developed genetic stratification for accurate
      quantitative estimation of TSPO using second-generation PET radioligands. In this
      study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the
      lesional, perilesional, and surrounding normal-appearing white matter of MS
      patients, as an index of the innate immune response. METHODS: (18)F-PBR111
      binding was quantified in 11 MS patients and 11 age-matched healthy volunteers,
      stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated
      inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to
      segment the white matter in MS patients as lesions, perilesional volumes,
      nonlesional white matter with reduced MTR, and nonlesional white matter with
      normal MTR. RESULTS: (18)F-PBR111 binding was higher in the white matter lesions
      and perilesional volumes of MS patients than in white matter of healthy controls
      (P < 0.05). Although there was substantial heterogeneity in binding between
      different lesions, a within-subject analysis showed higher (18)F-PBR111 binding
      in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white
      matter with reduced MTR (P < 0.005) than in nonlesional white matter with a
      normal MTR. A positive correlation was observed between the mean (18)F-PBR111
      volume of distribution increase in lesions relative to nonlesional white matter
      with a normal MTR and the MS severity score (Spearman rho = 0.62, P < 0.05).
      CONCLUSION: This study demonstrates that quantitative TSPO PET with a second
      generation radioligand can be used to characterize innate immune responses in MS
      in vivo and provides further evidence supporting an association between the white
      matter TSPO PET signal in lesions and disease severity. Our approach is practical
      for extension to studies of the role of the innate immune response in MS for
      differentiation of antiinflammatory effects of new medicines and their longer
      term impact on clinical outcome.

PMID- 24904113
TI  - Visual versus quantitative assessment of intratumor 18F-FDG PET uptake
      heterogeneity: prognostic value in non-small cell lung cancer.
AB  - The goal of this study was to compare visual assessment of intratumor (18)F-FDG
      PET uptake distribution with a textural-features (TF) automated quantification
      and to establish their respective prognostic value in non-small cell lung cancer
      (NSCLC). METHODS: The study retrospectively included 102 consecutive patients.
      Only primary tumors were considered. Intratumor heterogeneity was visually scored
      (3-level scale [Hvisu]) by 2 nuclear medicine physicians. Tumor volumes were
      automatically delineated, and heterogeneity was quantified with TF. Mean and
      maximum standardized uptake value were also included. Visual interobserver
      agreement and correlations with quantitative assessment were evaluated using the
      kappa test and Spearman rank (rho) coefficient, respectively. Association with
      overall survival and recurrence-free survival was investigated using the Kaplan
      Meier method and Cox regression models. RESULTS: Moderate correlations (0.4 < rho
      < 0.6) between TF parameters and Hvisu were observed. Interobserver agreement for
      Hvisu was moderate (kappa = 0.64, discrepancies in 27% of the cases). High
      standardized uptake value, large metabolic volumes, and high heterogeneity
      according to TF were associated with poorer overall survival and recurrence-free
      survival and remained an independent prognostic factor of overall survival with
      respect to clinical variables. CONCLUSION: Quantification of (18)F-FDG uptake
      heterogeneity in NSCLC through TF was correlated with visual assessment by
      experts. However, TF also constitutes an objective heterogeneity quantification,
      with reduced interobserver variability, and independent prognostic value
      potentially useful for patient stratification and management.

PMID- 24904114
TI  - Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1
      in zebrafish.
AB  - Type 2 diabetes, obesity, and metabolic syndrome are pathologies where insulin
      resistance plays a central role, and that affect a large population worldwide.
      These pathologies are usually associated with a dysregulation of insulin
      secretion leading to a chronic exposure of the tissues to high insulin levels
      (i.e. hyperinsulinemia), which diminishes the concentration of key downstream
      elements, causing insulin resistance. The complexity of the study of insulin
      resistance arises from the heterogeneity of the metabolic states where it is
      observed. To contribute to the understanding of the mechanisms triggering insulin
      resistance, we have developed a zebrafish model to study insulin metabolism and
      its associated disorders. Zebrafish larvae appeared to be sensitive to human
      recombinant insulin, becoming insulin-resistant when exposed to a high dose of
      the hormone. Moreover RNA-seq-based transcriptomic profiling of these larvae
      revealed a strong downregulation of a number of immune-relevant genes as a
      consequence of the exposure to hyperinsulinemia. Interestingly, as an exception,
      the negative immune modulator protein tyrosine phosphatase nonreceptor type 6
      (ptpn6) appeared to be upregulated in insulin-resistant larvae. Knockdown of
      ptpn6 was found to counteract the observed downregulation of the immune system
      and insulin signaling pathway caused by hyperinsulinemia. These results indicate
      that ptpn6 is a mediator of the metabolic switch between insulin-sensitive and
      insulin-resistant states. Our zebrafish model for hyperinsulinemia has therefore
      demonstrated its suitability for discovery of novel regulators of insulin
      resistance. In addition, our data will be very useful in further studies of the
      function of immunological determinants in a non-obese model system. 

PMID- 24904115
TI  - Matriptase-2 is essential for hepcidin repression during fetal life and postnatal
      development in mice to maintain iron homeostasis.
AB  - Iron is an essential element required for development and survival of all living
      organisms. In fetuses, maternofetal iron transfer across the placenta is
      essential for growth and development. In neonates, efficient intestinal iron
      absorption is required to scavenge as much iron as possible from the low-iron
      content milk. During these periods, efficient iron mobilization is ensured by the
      downregulation of the iron regulatory hormone hepcidin by as-yet uncharacterized
      molecular mechanisms. Here we demonstrate that the recently described hepcidin
      repressor-the serine protease matriptase-2 (encoded by Tmprss6)-is responsible
      for this repression throughout development, with its deficiency leading to
      increased hepcidin levels triggering iron deficiency and anemia starting in
      utero. This result might have implications for a better understanding of iron
      homeostasis during early development in iron-refractory iron deficiency anemia
      patients, who present with microcytic anemia caused by hyperhepcidinemia, and of
      questions about the role of matriptase-2 in human neonates. 

PMID- 24904116
TI  - Infection-related mortality in children with acute lymphoblastic leukemia: an
      analysis of infectious deaths on UKALL2003.
AB  - Although infection is the major cause of treatment-related mortality (TRM) in
      childhood acute lymphoblastic leukemia, factors associated with infection-related
      mortality (IRM) are poorly understood. To address this, we report an analysis of
      all 75 cases of IRM in the United Kingdom Childhood Acute Lymphoblastic Leukaemia
      Randomised Trial 2003 (UKALL 2003). The 5-year cumulative incidence of IRM was
      2.4% (95% confidence interval [CI], 1.9%-3.0%), accounting for 75 (30%) of 249
      trial deaths and 75 (64%) of 117 TRM deaths. Risk for IRM as a proportion of TRM
      was greater in induction than other phases (77% vs 56%; P = .02). Sixty-eight
      percent of cases were associated with bacterial infection (64% Gram-negative) and
      20% with fungal infection. Down syndrome was the most significant risk factor for
      IRM (odds ratio [OR], 12.08; 95% CI, 6.54-22.32; P < .0001). In addition, there
      was a trend toward increased IRM in girls (OR, 1.63; 95% CI, 1.02-2.61; P = .04),
      as well as increasing treatment intensity (regimen B vs A: OR, 2.11 [95% CI, 1.24
      3.60]; regimen C vs A: OR, 1.41 [95% CI, 0.76-2.62]; P = .02). Importantly,
      patients with Down syndrome were at significantly higher risk for IRM during
      maintenance (P = .048). Our results confirm Down syndrome as a major risk factor
      for IRM. Enhanced supportive care and prophylactic antibiotics should be
      considered in high-risk patient groups and during periods of increased risk. This
      study was registered at http://www.controlled-trials.com/ as #ISRCTN07355119. 

PMID- 24904117
TI  - PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by
      illegitimate RAG-mediated recombination events.
AB  - Phosphatase and tensin homolog (PTEN)-inactivating mutations and/or deletions are
      an independent risk factor for relapse of T-cell acute lymphoblastic leukemia (T
      ALL) patients treated on Dutch Childhood Oncology Group or German Cooperative
      Study Group for Childhood Acute Lymphoblastic Leukemia protocols. Some
      monoallelic mutated or PTEN wild-type patients lack PTEN protein, implying that
      additional PTEN inactivation mechanisms exist. We show that PTEN is inactivated
      by small deletions affecting a few exons in 8% of pediatric T-ALL patients. These
      microdeletions were clonal in 3% and subclonal in 5% of patients. Conserved
      deletion breakpoints are flanked by cryptic recombination signal sequences
      (cRSSs) and frequently have non-template-derived nucleotides inserted in between
      breakpoints, pointing to an illegitimate RAG recombination-driven activity.
      Identified cRSSs drive RAG-dependent recombination in a reporter system as
      efficiently as bona fide RSSs that flank gene segments of the T-cell receptor
      locus. Remarkably, equivalent microdeletions were detected in thymocytes of
      healthy individuals. Microdeletions strongly associate with the TALLMO subtype
      characterized by TAL1 or LMO2 rearrangements. Primary and secondary
      xenotransplantation of TAL1-rearranged leukemia allowed development of leukemic
      subclones with newly acquired PTEN microdeletions. Ongoing RAG activity may
      therefore actively contribute to the acquisition of preleukemic hits, clonal
      diversification, and disease progression. 

PMID- 24904118
TI  - HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression.
AB  - Mutations in HFE are the most common cause of hereditary hemochromatosis (HH).
      HFE mutations result in reduced expression of hepcidin, a hepatic hormone, which
      negatively regulates iron absorption from the duodenum and iron release from
      macrophages. However, the mechanism by which HFE regulates hepcidin expression in
      hepatocytes is not well understood. It is known that the bone morphogenetic
      protein (BMP) pathway plays a central role in controlling hepcidin expression in
      the liver. Here we show that HFE overexpression increased Smad1/5/8
      phosphorylation and hepcidin expression, whereas inhibition of BMP signaling
      abolished HFE-induced hepcidin expression in Hep3B cells. HFE was found to
      associate with ALK3, inhibiting ALK3 ubiquitination and proteasomal degradation
      and increasing ALK3 protein expression and accumulation on the cell surface. The
      2 HFE mutants associated with HH, HFE C282Y and HFE H63D, regulated ALK3 protein
      ubiquitination and trafficking differently, but both failed to increase ALK3 cell
      surface expression. Deletion of Hfe in mice resulted in a decrease in hepatic
      ALK3 protein expression. Our results provide evidence that HFE induces hepcidin
      expression via the BMP pathway: HFE interacts with ALK3 to stabilize ALK3 protein
      and increase ALK3 expression at the cell surface. 

PMID- 24904119
TI  - A tour through the transcriptional landscape of platelets.
AB  - The RNA code found within a platelet and alterations of that code continue to
      shed light onto the mechanistic underpinnings of platelet function and
      dysfunction. It is now known that features of messenger RNA (mRNA) in platelets
      mirror those of nucleated cells. This review serves as a tour guide for readers
      interested in developing a greater understanding of platelet mRNA. The tour
      provides an in-depth and interactive examination of platelet mRNA, especially in
      the context of next-generation RNA sequencing. At the end of the expedition, the
      reader will have a better grasp of the topography of platelet mRNA and how it
      impacts platelet function in health and disease. 

PMID- 24904122
TI  - Weight gain is greater with some antidepressants than others, US study finds.

PMID- 24904121
TI  - Modeling visual clutter perception using proto-object segmentation.
AB  - We introduce the proto-object model of visual clutter perception. This
      unsupervised model segments an image into superpixels, then merges neighboring
      superpixels that share a common color cluster to obtain proto-objects-defined
      here as spatially extended regions of coherent features. Clutter is estimated by
      simply counting the number of proto-objects. We tested this model using 90 images
      of realistic scenes that were ranked by observers from least to most cluttered.
      Comparing this behaviorally obtained ranking to a ranking based on the model
      clutter estimates, we found a significant correlation between the two (Spearman's
      rho = 0.814, p < 0.001). We also found that the proto-object model was highly
      robust to changes in its parameters and was generalizable to unseen images. We
      compared the proto-object model to six other models of clutter perception and
      demonstrated that it outperformed each, in some cases dramatically. Importantly,
      we also showed that the proto-object model was a better predictor of clutter
      perception than an actual count of the number of objects in the scenes,
      suggesting that the set size of a scene may be better described by proto-objects
      than objects. We conclude that the success of the proto-object model is due in
      part to its use of an intermediate level of visual representation-one between
      features and objects-and that this is evidence for the potential importance of a
      proto-object representation in many common visual percepts and tasks.

PMID- 24904120
TI  - Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor
      ixazomib in relapsed/refractory multiple myeloma.
AB  - Proteasome inhibition is an effective treatment strategy for multiple myeloma.
      With improving survival, attention is increasingly focusing on ease of
      administration and toxicity profile. Ixazomib is an investigational, orally
      bioavailable 20S proteasome inhibitor. Sixty patients with relapsed and/or
      refractory multiple myeloma were enrolled on this phase 1 trial to evaluate
      safety and tolerability and determine the maximum tolerated dose (MTD) of single
      agent, oral ixazomib given weekly for 3 of 4 weeks. Upon MTD determination,
      patients were enrolled to 4 different cohorts based on relapsed/refractory status
      and prior bortezomib and carfilzomib exposure. The MTD was determined to be 2.97
      mg/m(2). Dose-limiting toxicities were grade 3 nausea, vomiting, and diarrhea in
      2 patients, and grade 3 skin rash in 1 patient. Common drug-related adverse
      events were thrombocytopenia (43%), diarrhea (38%), nausea (38%), fatigue (37%),
      and vomiting (35%). The observed rate of peripheral neuropathy was 20%, with only
      1 grade 3 event reported. Nine (18%) patients achieved a partial response or
      better, including 8 of 30 (27%) evaluable patients treated at the MTD.
      Pharmacokinetic studies suggested a long terminal half-life of 3.6 to 11.3 days,
      supporting once-weekly dosing. This trial was registered at
      www.clinicaltrials.gov as #NCT00963820. 

PMID- 24904123
TI  - Digging for data on harms in duloxetine trials.

PMID- 24904124
TI  - Schizophrenia is associated with increased rates of violence and suicide, Swedish
      study finds.

PMID- 24904125
TI  - Transthoracic echocardiogram in a parasternal long axis window.

PMID- 24904126
TI  - Science diplomacy with Cuba.

PMID- 24904131
TI  - Interview. Kickoff looms for demo of brain-controlled machine.

PMID- 24904132
TI  - Climate change. A bold baby step on emissions.

PMID- 24904134
TI  - Reproductive biology. Gearing up for a closer look at the human placenta.

PMID- 24904133
TI  - Cell biology. Lengthy RNAs earn respect as cellular players.

PMID- 24904135
TI  - Materials science. Solar furnace rises from the Soviet ashes in Central Asia.

PMID- 24904136
TI  - Minority voice.

PMID- 24904137
TI  - The killing ground.

PMID- 24904139
TI  - Planetary science. Speed metal.

PMID- 24904138
TI  - Ecology. Change is coming to the northern oceans.

PMID- 24904140
TI  - Neuroscience. Memories--getting wired during sleep.

PMID- 24904141
TI  - Atmospheric science. Just add aerosols.

PMID- 24904142
TI  - Agriculture policy. EU agricultural reform fails on biodiversity.

PMID- 24904143
TI  - Evolution. Energy at life's origin.

PMID- 24904144
TI  - Interfacial chemistry. Disrupting dissolving ions at surfaces with fluid flow.

PMID- 24904145
TI  - Plant science. Best practices for biofuels.

PMID- 24904146
TI  - Overlooked local biodiversity loss.

PMID- 24904147
TI  - Overlooked local biodiversity loss--response.

PMID- 24904148
TI  - Talk therapy results speak for themselves.

PMID- 24904150
TI  - Response to Comment on "Engineering coherence among excited states in synthetic
      heterodimer systems".
AB  - Halpin, Johnson, and Miller contest our assignment of quantum beating signals
      observed in the two-dimensional electronic spectra of a series of fluorescein
      heterodimers to electronic coherences. Here, we present resonance Raman spectra,
      statistical analysis on multiple data sets, and an explanation of differences
      between the family of molecules described in our Report and the homodimer
      examined by the commenters. We contend that these results all support our
      assignment of the beating signals to electronic coherences. 

PMID- 24904149
TI  - Comment on "Engineering coherence among excited states in synthetic heterodimer
      systems".
AB  - Hayes et al. (Reports, 21 June 2013, p. 1431) used two-dimensional (2D)
      electronic spectroscopy to study molecular heterodimers and reported a general
      mechanism for the prolongation of electronic coherences, consistent with previous
      interpretations of 2D spectra for light-harvesting systems. We argue that the
      dynamics attributed to electronic coherences are inconclusive based on
      experimental inconsistencies arising from limited sample characterization and
      insufficient control measurements. 

PMID- 24904151
TI  - The global supply chain. Rethinking the global supply chain. Introduction.

PMID- 24904152
TI  - The information highway gets physical.

PMID- 24904153
TI  - The whole chain.

PMID- 24904154
TI  - Emerging approaches, challenges and opportunities in life cycle assessment.
AB  - In the modern economy, international value chains--production, use, and disposal
      of goods--have global environmental impacts. Life Cycle Assessment (LCA) aims to
      track these impacts and assess them from a systems perspective, identifying
      strategies for improvement without burden shifting. We review recent developments
      in LCA, including existing and emerging applications aimed at supporting
      environmentally informed decisions in policy-making, product development and
      procurement, and consumer choices. LCA constitutes a viable screening tool that
      can pinpoint environmental hotspots in complex value chains, but we also caution
      that completeness in scope comes at the price of simplifications and
      uncertainties. Future advances of LCA in enhancing regional detail and accuracy
      as well as broadening the assessment to economic and social aspects will make it
      more relevant for producers and consumers alike.

PMID- 24904155
TI  - Humanity's unsustainable environmental footprint.
AB  - Within the context of Earth's limited natural resources and assimilation
      capacity, the current environmental footprint of humankind is not sustainable.
      Assessing land, water, energy, material, and other footprints along supply chains
      is paramount in understanding the sustainability, efficiency, and equity of
      resource use from the perspective of producers, consumers, and government. We
      review current footprints and relate those to maximum sustainable levels,
      highlighting the need for future work on combining footprints, assessing trade
      offs between them, improving computational techniques, estimating maximum
      sustainable footprint levels, and benchmarking efficiency of resource use.
      Ultimately, major transformative changes in the global economy are necessary to
      reduce humanity's environmental footprint to sustainable levels. 

PMID- 24904157
TI  - The science of sustainable supply chains.
AB  - Recent advances in the science and technology of global supply chain management
      offer near-real-time demand-response systems for decision-makers across
      production networks. Technology is helping propel "fast fashion" and "lean
      manufacturing," so that companies are better able to deliver products consumers
      want most. Yet companies know much less about the environmental and social
      impacts of their production networks. The failure to measure and manage these
      impacts can be explained in part by limitations in the science of sustainability
      measurement, as well as by weaknesses in systems to translate data into
      information that can be used by decision-makers inside corporations and
      government agencies. There also remain continued disincentives for firms to
      measure and pay the full costs of their supply chain impacts. I discuss the
      current state of monitoring, measuring, and analyzing information related to
      supply chain sustainability, as well as progress that has been made in
      translating this information into systems to advance more sustainable practices
      by corporations and consumers. Better data, decision-support tools, and
      incentives will be needed to move from simply managing supply chains for costs,
      compliance, and risk reduction to predicting and preventing unsustainable
      practices. 

PMID- 24904156
TI  - Slowing Amazon deforestation through public policy and interventions in beef and
      soy supply chains.
AB  - The recent 70% decline in deforestation in the Brazilian Amazon suggests that it
      is possible to manage the advance of a vast agricultural frontier. Enforcement of
      laws, interventions in soy and beef supply chains, restrictions on access to
      credit, and expansion of protected areas appear to have contributed to this
      decline, as did a decline in the demand for new deforestation. The supply chain
      interventions that fed into this deceleration are precariously dependent on
      corporate risk management, and public policies have relied excessively on
      punitive measures. Systems for delivering positive incentives for farmers to
      forgo deforestation have been designed but not fully implemented. Territorial
      approaches to deforestation have been effective and could consolidate progress in
      slowing deforestation while providing a framework for addressing other important
      dimensions of sustainable development. 

PMID- 24904159
TI  - Electrically driven nuclear spin resonance in single-molecule magnets.
AB  - Recent advances in addressing isolated nuclear spins have opened up a path toward
      using nuclear-spin-based quantum bits. Local magnetic fields are normally used to
      coherently manipulate the state of the nuclear spin; however, electrical
      manipulation would allow for fast switching and spatially confined spin control.
      Here, we propose and demonstrate coherent single nuclear spin manipulation using
      electric fields only. Because there is no direct coupling between the spin and
      the electric field, we make use of the hyperfine Stark effect as a magnetic field
      transducer at the atomic level. This quantum-mechanical process is present in all
      nuclear spin systems, such as phosphorus or bismuth atoms in silicon, and offers
      a general route toward the electrical control of nuclear-spin-based devices. 

PMID- 24904158
TI  - Structural basis for a pH-sensitive calcium leak across membranes.
AB  - Calcium homeostasis balances passive calcium leak and active calcium uptake.
      Human Bax inhibitor-1 (hBI-1) is an antiapoptotic protein that mediates a calcium
      leak and is representative of a highly conserved and widely distributed family,
      the transmembrane Bax inhibitor motif (TMBIM) proteins. Here, we present crystal
      structures of a bacterial homolog and characterize its calcium leak activity. The
      structure has a seven-transmembrane-helix fold that features two triple-helix
      sandwiches wrapped around a central C-terminal helix. Structures obtained in
      closed and open conformations are reversibly interconvertible by change of pH. A
      hydrogen-bonded, pKa (where Ka is the acid dissociation constant)-perturbed pair
      of conserved aspartate residues explains the pH dependence of this transition,
      and biochemical studies show that pH regulates calcium influx in proteoliposomes.
      Homology models for hBI-1 provide insights into TMBIM-mediated calcium leak and
      cytoprotective activity. 

PMID- 24904160
TI  - Liquid flow along a solid surface reversibly alters interfacial chemistry.
AB  - In nature, aqueous solutions often move collectively along solid surfaces (for
      example, raindrops falling on the ground and rivers flowing through riverbeds).
      However, the influence of such motion on water-surface interfacial chemistry is
      unclear. In this work, we combine surface-specific sum frequency generation
      spectroscopy and microfluidics to show that at immersed calcium fluoride and
      fused silica surfaces, flow leads to a reversible modification of the surface
      charge and subsequent realignment of the interfacial water molecules. Obtaining
      equivalent effects under static conditions requires a substantial change in bulk
      solution pH (up to 2 pH units), demonstrating the coupling between flow and
      chemistry. These marked flow-induced variations in interfacial chemistry should
      substantially affect our understanding and modeling of chemical processes at
      immersed surfaces. 

PMID- 24904161
TI  - From aerosol-limited to invigoration of warm convective clouds.
AB  - Among all cloud-aerosol interactions, the invigoration effect is the most
      elusive. Most of the studies that do suggest this effect link it to deep
      convective clouds with a warm base and cold top. Here, we provide evidence from
      observations and numerical modeling of a dramatic aerosol effect on warm clouds.
      We propose that convective-cloud invigoration by aerosols can be viewed as an
      extension of the concept of aerosol-limited clouds, where cloud development is
      limited by the availability of cloud-condensation nuclei. A transition from
      pristine to slightly polluted atmosphere yields estimated negative forcing of ~15
      watts per square meter (cooling), suggesting that a substantial part of this
      anthropogenic forcing over the oceans occurred at the beginning of the industrial
      era, when the marine atmosphere experienced such transformation. 

PMID- 24904162
TI  - Identification of the giant impactor Theia in lunar rocks.
AB  - The Moon was probably formed by a catastrophic collision of the proto-Earth with
      a planetesimal named Theia. Most numerical models of this collision imply a
      higher portion of Theia in the Moon than in Earth. Because of the isotope
      heterogeneity among solar system bodies, the isotopic composition of Earth and
      the Moon should thus be distinct. So far, however, all attempts to identify the
      isotopic component of Theia in lunar rocks have failed. Our triple oxygen isotope
      data reveal a 12 +/- 3 parts per million difference in Delta(17)O between Earth
      and the Moon, which supports the giant impact hypothesis of Moon formation. We
      also show that enstatite chondrites and Earth have different Delta(17)O values,
      and we speculate on an enstatite chondrite-like composition of Theia. The
      observed small compositional difference could alternatively be explained by a
      carbonaceous chondrite-dominated late veneer. 

PMID- 24904163
TI  - Protracted core formation and rapid accretion of protoplanets.
AB  - Understanding core formation in meteorite parent bodies is critical for
      constraining the fundamental processes of protoplanet accretion and
      differentiation within the solar protoplanetary disk. We report variations of 5
      to 20 parts per million in (182)W, resulting from the decay of now-extinct
      (182)Hf, among five magmatic iron meteorite groups. These (182)W variations
      indicate that core formation occurred over an interval of ~1 million years and
      may have involved an early segregation of Fe-FeS and a later segregation of Fe
      melts. Despite this protracted interval of core formation, the iron meteorite
      parent bodies probably accreted concurrently ~0.1 to 0.3 million years after the
      formation of Ca-Al-rich inclusions. Variations in volatile contents among these
      bodies, therefore, did not result from accretion at different times from an
      incompletely condensed solar nebula but must reflect local processes within the
      nebula. 

PMID- 24904164
TI  - Marine teleost locates live prey through pH sensing.
AB  - We report that the Japanese sea catfish Plotosus japonicus senses local pH
      associated increases in H(+)/CO2 equating to a decrease of <=0.1 pH unit in
      ambient seawater. We demonstrated that these sensors, located on the external
      body of the fish, detect undamaged cryptic respiring prey, such as polychaete
      worms. Sensitivity is maximal at the natural pH of seawater (pH 8.1 to 8.2) and
      decreases dramatically in seawater with a pH <8.0. 

PMID- 24904165
TI  - Defining an essential transcription factor program for naive pluripotency.
AB  - The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells
      choose between self-renewal and differentiation appears vast and has yet to be
      distilled into an executive molecular program. We developed a data-constrained,
      computational approach to reduce complexity and to derive a set of functionally
      validated components and interaction combinations sufficient to explain observed
      ES cell behavior. This minimal set, the simplest version of which comprises only
      16 interactions, 12 components, and three inputs, satisfies all prior
      specifications for self-renewal and furthermore predicts unknown and nonintuitive
      responses to compound genetic perturbations with an overall accuracy of 70%. We
      propose that propagation of ES cell identity is not determined by a vast
      interactome but rather can be explained by a relatively simple process of
      molecular computation. 

PMID- 24904166
TI  - A mutually assured destruction mechanism attenuates light signaling in
      Arabidopsis.
AB  - After light-induced nuclear translocation, phytochrome photoreceptors interact
      with and induce rapid phosphorylation and degradation of basic helix-loop-helix
      transcription factors, such as PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), to
      regulate gene expression. Concomitantly, this interaction triggers feedback
      reduction of phytochrome B (phyB) levels. Light-induced phosphorylation of PIF3
      is necessary for the degradation of both proteins. We report that this PIF3
      phosphorylation induces, and is necessary for, recruitment of LRB [Light-Response
      Bric-a-Brack/Tramtrack/Broad (BTB)] E3 ubiquitin ligases to the PIF3-phyB
      complex. The recruited LRBs promote concurrent polyubiqutination and degradation
      of both PIF3 and phyB in vivo. These data reveal a linked signal-transmission and
      attenuation mechanism involving mutually assured destruction of the receptor and
      its immediate signaling partner. 

PMID- 24904167
TI  - Caspase-mediated cleavage of phospholipid flippase for apoptotic
      phosphatidylserine exposure.
AB  - Phospholipids are asymmetrically distributed in the plasma membrane. This
      asymmetrical distribution is disrupted during apoptosis, exposing
      phosphatidylserine (PtdSer) on the cell surface. Using a haploid genetic screen
      in human cells, we found that ATP11C (adenosine triphosphatase type 11C) and
      CDC50A (cell division cycle protein 50A) are required for aminophospholipid
      translocation from the outer to the inner plasma membrane leaflet; that is, they
      display flippase activity. ATP11C contained caspase recognition sites, and
      mutations at these sites generated caspase-resistant ATP11C without affecting its
      flippase activity. Cells expressing caspase-resistant ATP11C did not expose
      PtdSer during apoptosis and were not engulfed by macrophages, which suggests that
      inactivation of the flippase activity is required for apoptotic PtdSer exposure.
      CDC50A-deficient cells displayed PtdSer on their surface and were engulfed by
      macrophages, indicating that PtdSer is sufficient as an "eat me" signal. 

PMID- 24904169
TI  - Sleep promotes branch-specific formation of dendritic spines after learning.
AB  - How sleep helps learning and memory remains unknown. We report in mouse motor
      cortex that sleep after motor learning promotes the formation of postsynaptic
      dendritic spines on a subset of branches of individual layer V pyramidal neurons.
      New spines are formed on different sets of dendritic branches in response to
      different learning tasks and are protected from being eliminated when multiple
      tasks are learned. Neurons activated during learning of a motor task are
      reactivated during subsequent non-rapid eye movement sleep, and disrupting this
      neuronal reactivation prevents branch-specific spine formation. These findings
      indicate that sleep has a key role in promoting learning-dependent synapse
      formation and maintenance on selected dendritic branches, which contribute to
      memory storage. 

PMID- 24904170
TI  - Specific disruption of thalamic inputs to the auditory cortex in schizophrenia
      models.
AB  - Auditory hallucinations in schizophrenia are alleviated by antipsychotic agents
      that inhibit D2 dopamine receptors (Drd2s). The defective neural circuits and
      mechanisms of their sensitivity to antipsychotics are unknown. We identified a
      specific disruption of synaptic transmission at thalamocortical glutamatergic
      projections in the auditory cortex in murine models of schizophrenia-associated
      22q11 deletion syndrome (22q11DS). This deficit is caused by an aberrant
      elevation of Drd2 in the thalamus, which renders 22q11DS thalamocortical
      projections sensitive to antipsychotics and causes a deficient acoustic startle
      response similar to that observed in schizophrenic patients. Haploinsufficiency
      of the microRNA-processing gene Dgcr8 is responsible for the Drd2 elevation and
      hypersensitivity of auditory thalamocortical projections to antipsychotics. This
      suggests that Dgcr8-microRNA-Drd2-dependent thalamocortical disruption is a
      pathogenic event underlying schizophrenia-associated psychosis. 

PMID- 24904171
TI  - On the road again.

PMID- 24904168
TI  - The sheep genome illuminates biology of the rumen and lipid metabolism.
AB  - Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of
      wool and represent a distinct class of animals that have a specialized digestive
      organ, the rumen, that carries out the initial digestion of plant material. We
      have developed and analyzed a high-quality reference sheep genome and
      transcriptomes from 40 different tissues. We identified highly expressed genes
      encoding keratin cross-linking proteins associated with rumen evolution. We also
      identified genes involved in lipid metabolism that had been amplified and/or had
      altered tissue expression patterns. This may be in response to changes in the
      barrier lipids of the skin, an interaction between lipid metabolism and wool
      synthesis, and an increased role of volatile fatty acids in ruminants compared
      with nonruminant animals. 

PMID- 24904172
TI  - Proneural transcription factor Atoh1 drives highly efficient differentiation of
      human pluripotent stem cells into dopaminergic neurons.
AB  - Human pluripotent stem cells (PSCs) are a promising cell resource for various
      applications in regenerative medicine. Highly efficient approaches that
      differentiate human PSCs into functional lineage-specific neurons are critical
      for modeling neurological disorders and testing potential therapies. Proneural
      transcription factors are crucial drivers of neuron development and hold promise
      for driving highly efficient neuronal conversion in PSCs. Here, we study the
      functions of proneural transcription factor Atoh1 in the neuronal differentiation
      of PSCs. We show that Atoh1 is induced during the neuronal conversion of PSCs and
      that ectopic Atoh1 expression is sufficient to drive PSCs into neurons with high
      efficiency. Atoh1 induction, in combination with cell extrinsic factors,
      differentiates PSCs into functional dopaminergic (DA) neurons with >80% purity.
      Atoh1-induced DA neurons recapitulate key biochemical and electrophysiological
      features of midbrain DA neurons, the degeneration of which is responsible for
      clinical symptoms in Parkinson's disease (PD). Atoh1-induced DA neurons provide a
      reliable disease model for studying PD pathogenesis, such as neurotoxin-induced
      neurodegeneration in PD. Overall, our results determine the role of Atoh1 in
      regulating neuronal differentiation and neuron subtype specification of human
      PSCs. Our Atoh1-mediated differentiation approach will enable large-scale
      applications of PD patient-derived midbrain DA neurons in mechanistic studies and
      drug screening for both familial and sporadic PD. 

PMID- 24904173
TI  - Efficient generation of integration-free human induced pluripotent stem cells
      from keratinocytes by simple transfection of episomal vectors.
AB  - Keratinocytes represent an easily accessible cell source for derivation of human
      induced pluripotent stem (hiPS) cells, reportedly achieving higher reprogramming
      efficiency than fibroblasts. However, most studies utilized a retroviral or
      lentiviral method for reprogramming of keratinocytes, which introduces
      undesirable transgene integrations into the host genome. Moreover, current
      protocols of generating integration-free hiPS cells from keratinocytes are mostly
      inefficient. In this paper, we describe a more efficient, simple-to-use, and cost
      effective method for generating integration-free hiPS cells from keratinocytes.
      Our improved method using lipid-mediated transfection achieved a reprogramming
      efficiency of ~0.14% on average. Keratinocyte-derived hiPS cells showed no
      integration of episomal vectors, expressed stem cell-specific markers and
      possessed potentials to differentiate into all three germ layers by in vitro
      embryoid body formation as well as in vivo teratoma formation. To our knowledge,
      this represents the most efficient method to generate integration-free hiPS cells
      from keratinocytes. 

PMID- 24904174
TI  - Concise review: breast cancer stem cells: regulatory networks, stem cell niches,
      and disease relevance.
AB  - Accumulating evidence has shown that cancer stem cells (CSCs), the cancer cells
      that have long-term proliferative potential and the ability to regenerate tumors
      with phenotypically heterogeneous cell types, are important mediators of tumor
      metastasis and cancer relapse. In breast cancer, these cells often possess
      attributes of cells that have undergone an epithelial-mesenchymal transition
      (EMT). Signaling networks mediated by microRNAs and EMT-inducing transcription
      factors connect the EMT program with the core stem cell regulatory machineries.
      These signaling networks are also regulated by extrinsic niche signals that
      induce and maintain CSCs, contributing to metastatic colonization and promoting
      the reactivation of dormant tumor cells. Targeting these CSC pathways is likely
      to improve the efficacy of conventional chemo- and radiotherapies. 

PMID- 24904176
TI  - Unusual redo mitral valve replacement for bleeding in Glanzmann thrombasthenia.
AB  - We report the case of 23-year-old man with mitral valve regurgitation and
      Glanzmann thrombasthenia, who underwent mechanical mitral valve replacement.
      Warfarin therapy was devastating, causing bilateral hemothorax, pericardial
      effusion, gastrointestinal bleeding, and hematuria. Redo mitral valve replacement
      with a biological prosthesis was required to resolve this critical situation. To
      our knowledge, this is the first report of mitral valve replacement in Glanzmann
      thrombasthenia, highlighting the danger of oral anticoagulation in this
      pathology. 

PMID- 24904175
TI  - Mesenchymal stromal cell therapy is associated with increased adenovirus
      associated but not cytomegalovirus-associated mortality in children with severe
      acute graft-versus-host disease.
AB  - Beneficial effects of mesenchymal stromal cells (MSCs) in patients with severe
      steroid-refractory acute graft-versus-host disease (aGvHD) have been reported.
      However, controversy exists about the effect of MSCs on virus-specific T cells.
      We evaluated 56 patients with grade II-IV aGvHD who responded to steroids (n =
      21) or were steroid refractory receiving either MSCs (n = 22) or other second
      line therapy (n = 13). Although the overall incidence of cytomegalovirus (CMV),
      Epstein-Barr virus, and human adenovirus (HAdV) infections was not significantly
      increased, HAdV infection was associated with decreased survival in children
      treated with MSCs. Thus, we investigated in vitro the effects of MSCs on virus
      specific T cells. Both CMV-specific and, to a lesser extent, HAdV-specific T-cell
      activation and proliferation were negatively affected by MSCs either after
      induction of a response in peripheral blood mononuclear cells (PBMCs) or after
      restimulation of virus-specific T-cell lines. In patient-derived PBMCs, CMV
      specific proliferative responses were greatly decreased on first-line treatment
      of aGvHD with systemic steroids and slowly recovered after MSC administration and
      tapering of steroids. HAdV-specific T-cell proliferation could not be detected.
      In contrast, the proportion of CMV- and HAdV-specific effector T cells, measured
      as interferon-gamma-secreting cells, remained stable or increased after treatment
      with MSCs. In conclusion, although in vitro experimental conditions indicated a
      negative impact of MSCs on CMV- and HAdV-specific T-cell responses, no solid
      evidence was obtained to support such an effect of MSCs on T-cell responses in
      vivo. Still, the susceptibility of steroid-refractory severe aGvHD patients to
      viral reactivation warrants critical viral monitoring during randomized
      controlled trials on second-line treatment including MSCs. 

PMID- 24904177
TI  - Finite element analysis to model complex mitral valve repair.
AB  - Although finite element analysis has been used to model simple mitral repair, it
      has not been used to model complex repair. A virtual mitral valve model was
      successful in simulating normal and abnormal valve function. Models were then
      developed to simulate an edge-to-edge repair and repair employing quadrangular
      resection. Stress contour plots demonstrated increased stresses along the mitral
      annulus, corresponding to the annuloplasty. The role of finite element analysis
      in guiding clinical practice remains undetermined. 

PMID- 24904178
TI  - Decomposing differences in medical care access among cancer survivors by race and
      ethnicity.
AB  - More research is needed to identify factors that explain why minority cancer
      survivors ages 18 to 64 are more likely to delay or forgo care when compared with
      whites. Data were merged from the 2000-2011 National Health Interview Survey to
      identify 12 125 adult survivors who delayed medical care. The Fairlie
      decomposition technique was applied to explore contributing factors that explain
      the differences. Compared with whites, Hispanics were more likely to delay care
      because of organizational barriers (odds ratio = 1.38; P < .05), and African
      Americans were more likely to delay medical care or treatment because of
      transportation barriers (odds ratio = 1.54; P < .001). The predicted probability
      of not receiving timely care because of each barrier was lowest among minorities.
      Age, insurance, perceived health, comorbidity, nativity, and year were
      significant factors that contributed to the disparities. Although expanded
      insurance coverage through the Affordable Care Act is expected to increase
      access, organizational factors and transportation play a major role. 

PMID- 24904180
TI  - Acute cardiotoxic effects of adjuvant trastuzumab treatment and its relation to
      oxidative stress.

PMID- 24904181
TI  - Correlation of carotid artery disease severity and vasomotor response of cerebral
      blood vessels.
AB  - We assessed reactivity of cerebral vessels on hypercapnia in patients with
      carotid occlusive disease. The effects of vascular risk factors on carotid
      atherosclerosis and vasomotor reactivity (VMR) of cerebral arterioles were also
      examined. Patients (n = 50) with carotid stenosis (>=30% in 1 or both sides) were
      included; 30 patients acted as controls. Hypertension, hyperlipidemia, diabetes,
      cardiac diseases, inflammation, and smoking were recorded. Vasomotor reactivity
      was assessed with the apnea test by transcranial Doppler ultrasonography and
      estimated by flow velocity changes in the middle cerebral artery before and after
      hypercapnia induction. Vasomotor reactivity was defined by the breath holding
      index, and values under 0.69 were considered critical for VMR impairment.
      Vasomotor reactivity reduction was significant (P = .004) in patients with severe
      carotid stenosis (>70%) and with symptomatic carotid disease (P < .05). The risk
      factors did not significantly influence VMR reduction. Severe carotid stenosis
      impairs VMR and may increase the risk of stroke, especially in symptomatic
      patients. 

PMID- 24904182
TI  - Association between nonalcoholic fatty liver disease and carotid artery
      inflammation evaluated by 18F-fluorodeoxyglucose positron emission tomography.
AB  - We assessed the association between nonalcoholic fatty liver disease (NAFLD) and
      carotid artery inflammation measured by (18)F-fluorodeoxyglucose (FDG) positron
      emission tomography/computed tomography. Participants were 755 consecutive
      otherwise healthy adult males who underwent a general health screening program.
      Carotid FDG uptake, represented as maximum target-to-background ratio, was
      increased with mild (n = 237; 1.61 +/- 0.14; P = .033) and moderate NAFLD (n =
      145; 1.63 +/- 0.16; P = .005) compared with controls (n = 373; 1.58 +/- 0.15). In
      patients aged >50 years, moderate NAFLD was the only independent risk factor for
      high carotid FDG uptake (odds ratio, 2.12; 95% confidence interval, 1.10-4.07; P
      = .001). Apparently healthy adult males with NAFLD have elevated carotid FDG
      uptake as well as increased carotid intima-media thickness, suggesting that they
      may be at an increased risk of having inflammatory atherosclerotic plaques in the
      carotid arteries. 

PMID- 24904183
TI  - Regimen-Related Distress, Medication Adherence, and Glycemic Control in Rural
      African American Women With Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Regimen-related emotional distress in patients with type 2 diabetes
      mellitus (T2DM) is associated with poor glycemic control, but the mediators of
      this relationship are not well described. OBJECTIVE: This cross-sectional study
      at baseline examines these relationships, including the specific role of
      medication adherence in rural African American women. METHODS: At baseline in the
      EMPOWER randomized trial, the investigators collected the following data: Regimen
      Related Distress (RRD; subscale of the validated Diabetes Distress Scale),
      diabetes medications, medication adherence using the Morisky Medication Adherence
      Scale, and hemoglobin A1C (A1C). RESULTS: The study enrolled 189 rural African
      American women with T2DM (mean age = 53 +/- 11 years, A1C = 9.1% +/- 1.8%, body
      mass index = 37.7% +/- 8.2%; 61% on insulin); 56% reported elevated RRD (mean >=
      3.0), and this was associated with significantly lower medication adherence (4.4
      vs 6.4, P < 0.001) and significantly higher A1C (9.5% vs 8.6%, P < 0.001). In
      multivariate modeling, both elevated RRD (exp beta = 2.1; 95% CI = 1.1-4.2; P <
      0.05) and lower medication adherence (exp beta = 3.3; 95% CI = 1.1-9.6; P < 0.05)
      were independently associated with higher A1C values. In mediation analysis,
      medication adherence was a significant mediator of the effects of RRD on A1C.
      CONCLUSION: Among rural African American women with T2DM, elevated levels of RRD
      were common and were associated with higher A1C values, in part via effects on
      medication adherence. Complex treatment regimens accompanied by psychological
      distress may be associated with poorer glycemic control.

PMID- 24904179
TI  - Management and 1-year outcomes of patients with atrial fibrillation in the Middle
      East: Gulf survey of atrial fibrillation events.
AB  - We describe management and outcomes of patients with nonvalvular atrial
      fibrillation (AF) in the Middle East. Consecutive patients with AF presenting to
      emergency departments (EDs) were prospectively enrolled. Among 1721 patients with
      nonvalvular AF, mean age was 59 +/- 16 years and 44% were women. Comorbidities
      were common such as hypertension (59%), diabetes (33%), and coronary artery
      disease (33%). Warfarin was not prescribed to 40% of patients with Congestive
      heart failure, Hypertension, Age, Diabetes mellitus, Stroke/TIA2 score of >=2.
      One-year rates of stroke/transient ischemic attack (TIA) and all-cause mortality
      were 4.2% and 15.3%, respectively. Warfarin use at hospital-ED discharge was
      independently associated with lower 1-year rate of stroke/TIA (odds ratio [OR],
      0.38; 95% confidence interval [CI], 0.17-0.85; P = .015) and all-cause mortality
      (OR, 0.51; 95% CI, 0.32-0.83; P = .006). Prior history of heart failure and
      peripheral vascular disease was independent mortality predictors. Our patients
      are relatively young with significant cardiovascular risk. Their anticoagulation
      treatment is suboptimal, and 1-year all-cause mortality and stroke/TIA event
      rates are relatively high. 

PMID- 24904184
TI  - Utilization of Pharmacist Responders as a Component of a Multidisciplinary Sepsis
      Bundle.
AB  - BACKGROUND: Sepsis and septic shock remain a significant burden on the US health
      care system. A multidisciplinary response system (Coordinated Response to Sepsis,
      CaRTS) that included a pharmacist responder was implemented for patients with
      newly suspected sepsis. OBJECTIVE: To evaluate the time to appropriate antibiotic
      administration among patients with the CaRTS intervention compared with
      historical controls. METHOD: The CaRTS intervention included an electronic order
      set as well as activation of a multidisciplinary team of pharmacy and nursing
      personnel to coordinate resuscitation and medication administration. The CaRTS
      group was compared to historical controls. The primary outcome of the study was
      the proportion of patients with appropriate antibiotic administration within 1
      hour of recognition of sepsis. Secondary outcomes included achievement of mean
      arterial pressure (MAP) >=65 mm Hg and central venous pressure (CVP) of 8 to 12
      mm Hg within 6 hours. RESULT: The CaRTS intervention was used for 49 patients and
      59 historical controls were included for analysis. Patients with the CaRTS
      intervention had a greater than 20 times higher odds of antibiotic administration
      within 1 hour compared with controls (odds ratio [OR] 22.4, 95% confidence
      interval [CI] 7.5-69) and were more likely to have a CVP >=8 mm Hg at 6 hours (OR
      2.4, 95% CI 1.0-5.6) compared with controls. CaRTS patients achieved
      statistically nonsignificant increases in MAP >=65 mm Hg (OR 2.2, 95% CI 0.7
      7.7). CONCLUSION: Utilization of a multidisciplinary sepsis bundle that included
      a pharmacist responder improved the proportion of patients receiving appropriate
      antibiotics within 1 hour of recognition of sepsis compared to historical
      controls.

PMID- 24904185
TI  - The Motherhood Penalty at Midlife: Long-Term Effects of Children on Women's
      Careers.
AB  - The authors build on prior research on the motherhood wage penalty to examine
      whether the career penalties faced by mothers change over the life course. They
      broaden the focus beyond wages to also consider labor force participation and
      occupational status and use data from the National Longitudinal Survey of Young
      Women to model the changing impact of motherhood as women age from their 20s to
      their 50s (n = 4,730). They found that motherhood is "costly" to women's careers,
      but the effects on all 3 labor force outcomes attenuate at older ages. Children
      reduce women's labor force participation, but this effect is strongest when women
      are younger, and is eliminated by the 40s and 50s. Mothers also seem able to
      regain ground in terms of occupational status. The wage penalty for having
      children varies by parity, persisting across the life course only for women who
      have 3 or more children.

PMID- 24904186
TI  - Nanopatterned Protein Films Directed by Ionic Complexation with Water-Soluble
      Diblock Copolymers.
AB  - The use of ionic interactions to direct both protein templating and block
      copolymer self-assembly into nanopatterned films with only aqueous processing
      conditions is demonstrated using block copolymers containing both thermally
      responsive and pH responsive blocks. Controlled reversible addition-fragmentation
      chain-transfer (RAFT) polymerization is employed to synthesize poly(N
      isopropylacrylamide-b-2-(dimethylamino)ethyl acrylate) (PNIPAM-b-PDMAEA) diblock
      copolymers. The pH-dependent ionic complexation between the fluorescent protein,
      mCherry, and the ionic PDMAEA block is established using dynamic light scattering
      (DLS) and UV-Vis spectroscopy. DLS shows that the size of the resulting
      coacervate micelles depends strongly on pH, while UV-Vis spectroscopy shows a
      correlation between the protein's absorption maximum and the ionic
      microenvironment. Zeta potential measurements clearly indicate the ionic nature
      of the complex-forming interactions. Spin casting was used to prepare
      nanostructured films from the protein-block copolymer coacervates. After film
      formation, the lower critical solution temperature (LCST) of the PNIPAM blocks
      allows the nanomaterial to be effectively immobilized in aqueous environments at
      physiological temperatures, enabling potential use as a controlled protein
      release material or polymer matrix for protein immobilization. At pH 9.2 and 7.8,
      the release rates are at least 10 times faster than that at pH 6.4 due to weaker
      interaction between protein and PNIPAM-b-PDMAEA (PND) diblock copolymer. Due to
      the ionic environment in which protein is confined, the majority of the protein
      (80%) remains active, independent of pH, even after having been dehydrated in
      vacuum and confined in the films.

PMID- 24904187
TI  - Partisan Activism and Access to Welfare in Lebanon.
AB  - How do welfare regimes function when state institutions are weak and ethnic or
      sectarian groups control access to basic services? This paper explores how people
      gain access to basic services in Lebanon, where sectarian political parties from
      all major religious communities are key providers of social assistance and
      services. Based on analyses of an original national survey (n= 1,911) as well as
      in-depth interviews with providers and other elites (n= 175) and beneficiaries of
      social programs (n= 135), I make two main empirical claims in the paper. First,
      political activism and a demonstrated commitment to a party are associated with
      access to social assistance; and second, higher levels of political activism may
      facilitate access to higher levels or quantities of aid, including food baskets
      and financial assistance for medical and educational costs. These arguments
      highlight how politics can mediate access to social assistance in direct ways and
      add new dimensions to scholarly debates about clientelism by focusing on contexts
      with politicized religious identities and by problematizing the actual goods and
      services exchanged.

PMID- 24904188
TI  - Manganese terpyridine artificial metalloenzymes for benzylic oxygenation and
      olefin epoxidation.
AB  - New catalysts for non-directed hydrocarbon functionalization have great potential
      in organic synthesis. We hypothesized that incorporating a Mn-terpyridine
      cofactor into a protein scaffold would lead to artificial metalloenzymes (ArMs)
      in which the selectivity of the Mn cofactor could be controlled by the protein
      scaffold. We designed and synthesized a maleimide-substituted Mn-terpyridine
      cofactor and demonstrated that this cofactor could be incorporated into two
      different scaffold proteins to generate the desired ArMs. The structure and
      reactivity of one of these ArMs was explored, and the broad oxygenation
      capability of the Mn-terpyridine catalyst was maintained, providing a robust
      platform for optimization of ArMs for selective hydrocarbon functionalization.

PMID- 24904189
TI  - Computerizing Audit Studies.
AB  - This paper briefly discusses the history, benefits, and shortcomings of
      traditional audit field experiments to study market discrimination. Specifically
      it identifies template bias and experimenter bias as major concerns in the
      traditional audit method, and demonstrates through an empirical example that
      computerization of a resume or correspondence audit can efficiently increase
      sample size and greatly mitigate these concerns. Finally, it presents a useful
      meta-tool that future researchers can use to create their own resume audits.

PMID- 24904191
TI  - Dispositional Mindfulness Co-varies with Self-Reported Positive Reappraisal.
AB  - Emerging research suggests that mindfulness is associated with positive
      reappraisal and that mindfulness practice may be a means of encouraging positive
      reappraisal capacities. These findings, linking mindfulness with the promotion of
      cognitive coping strategies, challenge traditional Western conceptualizations of
      mindfulness as non-discursive. This study explored the relationship between
      dispositional mindfulness and self-reported positive reappraisal across five
      distinct samples: a general sample of American adults, contemplative
      practitioners, college students chronic pain outpatients, and alcohol dependent
      inpatient. Results indicate that dispositional mindfulness is positively related
      with self-reported positive reappraisal in all five studies as well as in an
      aggregated analysis combining all five studies. Furthermore, a second set of
      analyses statistically controlling for factors previously associated with
      positive reappraisal (i.e., psychological well-being, positive affect, and
      positive refocusing), provided evidence that mindfulness is uniquely associated
      with self-reported positive reappraisal. While more research is needed to refine
      our understanding of the relationship between mindfulness and positive
      reappraisal, the present investigation contributes to the growing evidence base
      supporting the hypothesized link between dispositional mindfulness and self
      reported reappraisal by demonstrating a significant association between these
      constructs across a variety of samples and in the largest combined dataset on
      this phenomenon collected to date (N=819).

PMID- 24904190
TI  - Pain-Suppressed Behaviors in the Red-tailed Hawk 1 (Buteo jamaicensis).
AB  - Our ability to provide analgesia in wild and exotic patients is hampered by a
      lack of species-specific information on effective drugs and protocols. One
      contributing factor is the difficulty of applying data from traditional
      laboratory tests of nociception to clinical conditions frequently involving
      combinations of inflammatory, mechanical, and neuropathic pain. Pain-suppressed
      behaviors have become a valuable predictor of clinical utility in other species;
      in this study we extend this framework to red -tailed hawks in a wildlife
      hospital, in an attempt to develop a new, humane testing method for birds of
      prey. We scored six behaviors in hawks hospitalized either for orthopedic trauma
      or for non-painful conditions. These behaviors included: movement about the cage,
      grooming, head motions, foot shifts, beak clacks, and rouse. Movement, head
      motions, and beak clacks were all significantly reduced in hawks with recent
      orthopedic injury, but not in hawks with healed or minor injuries (P<0.05 for all
      behaviors). However, it should be noted that due to stringent admission criteria,
      and the difficulties inherent in studying naturally-occuring injury in wild
      patients, this study only included -subjects in four experimental groups, and
      this limited our ability to fully investigate confounds within our data. A follow
      up experiment was conducted to determine potential effects of buprenorphine, a mu
      opioid agonist, on the behaviors listed above. Buprenorphine in the absence of
      pain caused minor, non-significant decreases in most behaviors, and had no effect
      on head movement frequency. This suggests that head movements in particular may
      be sensitive to pain but not to sedative side-effects of buprenorphine. Overall,
      red -tailed hawks with recent orthopedic trauma show consistent and marked red
      uctions in several normal maintenance behaviors. Head movements, reported for the
      first time in this study as a potential marker of pain in birds, in particular
      seem to be insensitive to sedative side effects of buprenorphine, while being a
      sensitive measu re of affective state in hawks with painful injuries. These
      behaviors can be scored humanely and with minimal expense, and should be
      considered for further research on pain and analgesia in avian species.

PMID- 24904192
TI  - Synthesis and Properties of Heavy Chalcogen Analogues of the Texas Reds and
      Related Rhodamines.
AB  - Analogues of Texas red incorporating the heavy chalcogens S, Se, and Te atoms in
      the xanthylium core were prepared from the addition of aryl Grignard reagents to
      appropriate chalcogenoxanthone precursors. The xanthones were prepared via
      directed metalation of amide precursors, addition of dichalcogenide
      electrophiles, and electrophilic cyclization of the resulting chalcogenides with
      phosphorus oxychloride and triethylamine. The Texas red analogues incorporate two
      fused julolidine rings containing the rhodamine nitrogen atoms. Analogues
      containing two "half-julolidine" groups (a trimethyltetrahydroquinoline) and one
      julolidine and one "half-julolidine" were also prepared. The photophysics of the
      Texas red analogues were examined. The S-analogues were highly fluorescent, the
      Se-analogues generated single oxygen (1O2) efficiently upon irradiation, and the
      Te-analogues were easily oxidized to rhodamines with the telluroxide oxidation
      state. The tellurorhodamine telluroxides absorb at wavelengths >=690 nm and emit
      with fluorescence maxima >720 nm. A mesityl-substituted tellurorhodamine
      derivative localized in the mitochondria of Colo-26 cells (a murine colon
      carcinoma cell line) and was oxidized in vitro to the fluorescent telluroxide.

PMID- 24904193
TI  - Metal complexes with varying intramolecular hydrogen bonding networks.
AB  - Alfred Werner described the attributes of the primary and secondary coordination
      spheres in his development of coordination chemistry. To examine the effects of
      the secondary coordination sphere on coordination chemistry, a series of tripodal
      ligands containing differing numbers of hydrogen bond (H-bond) donors were used
      to examine the effects of H-bonds on Fe(II), Mn(II)-acetato, and Mn(III)-OH
      complexes. The ligands containing varying numbers of urea and amidate donors
      allowed for systematic changes in the secondary coordination spheres of the
      complexes. Two of the Fe(II) complexes that were isolated as their Bu4N+ salts
      formed dimers in the solid-state as determined by X-ray diffraction methods,
      which correlates with the number of H-bonds present in the complexes (i.e.,
      dimerization is favored as the number of H-bond donors increases). Electron
      paramagnetic resonance (EPR) studies suggested that the dimeric structures
      persist in acetonitrile. The Mn(II) complexes were all isolated as their acetato
      adducts. Furthermore, the synthesis of a rare Mn(III)-OH complex via dioxygen
      activation was achieved that contains a single intramolecular H-bond; its
      physical properties are discussed within the context of other Mn(III)-OH
      complexes.

PMID- 24904194
TI  - Bayesian Transformation Models for Multivariate Survival Data.
AB  - In this paper we propose a general class of gamma frailty transformation models
      for multivariate survival data. The transformation class includes the commonly
      used proportional hazards and proportional odds models. The proposed class also
      includes a family of cure rate models. Under an improper prior for the
      parameters, we establish propriety of the posterior distribution. A novel Gibbs
      sampling algorithm is developed for sampling from the observed data posterior
      distribution. A simulation study is conducted to examine the properties of the
      proposed methodology. An application to a data set from a cord blood
      transplantation study is also reported.

PMID- 24904195
TI  - Asking to Speak to Another: A Skill for Soliciting Survey Participation.
AB  - This paper is in the vein of applied conversation analysis, dealing with a
      problem of declining participation rates for survey interviews. When calling a
      household to request participation in a survey, interviewers may ask for a pre
      selected "sample person." We first explore how interviewers design this request
      in a more or less presumptive way, depending on how and when they identify
      themselves. Secondly, we analyze different linguistic structures that embody
      degrees of entitlement. Thirdly, we examine greeting items for their degree of
      ceremoniousness and in terms of what work they do when not part of an explicit
      greeting sequence. We examine other features of asking to speak to another as
      well, including "please" and references to the sample person. Our strategy for
      analyzing survey interview data is to explore the design of "switchboard"
      requests in ordinary telephone calls. We relate our analysis to previous research
      that addresses whether the detailed practices for asking to speak to another
      matter for obtaining consent to do an interview. We draw implications for
      obtaining participation in the survey interview and other kinds of phone call
      solicitations. Data in American English.

PMID- 24904196
TI  - Stress-induced mast cell activation in glabrous and hairy skin.
AB  - Mast cells play a key role in modulation of stress-induced cutaneous
      inflammation. In this study we investigate the impact of repeated exposure to
      stress on mast cell degranulation, in both hairy and glabrous skin. Adult male
      Wistar rats were randomly divided into four groups: Stress 1 day (n = 8), Stress
      10 days (n = 7), Stress 21 days (n = 6), and Control (n = 8). Rats in the stress
      groups were subjected to 2 h/day restraint stress. Subsequently, glabrous and
      hairy skin samples from animals of all groups were collected to assess mast cell
      degranulation by histochemistry and transmission electron microscopy. The impact
      of stress on mast cell degranulation was different depending on the type of skin
      and duration of stress exposure. Short-term stress exposure induced an
      amplification of mast cell degranulation in hairy skin that was maintained after
      prolonged exposure to stress. In glabrous skin, even though acute stress exposure
      had a profound stimulating effect on mast cell degranulation, it diminished
      progressively with long-term exposure to stress. The results of our study
      reinforce the view that mast cells are active players in modulating skin
      responses to stress and contribute to further understanding of pathophysiological
      mechanisms involved in stress-induced initiation or exacerbation of cutaneous
      inflammatory processes.

PMID- 24904197
TI  - Ouabain affects the expression of activation markers, cytokine production, and
      endocytosis of human monocytes.
AB  - Ouabain is a steroid capable of binding to and inhibiting Na(+),-K(+)-ATPase.
      Studies have demonstrated some actions of ouabain on immune cells, which
      indicated both pro- and anti-inflammatory properties of this molecule.
      Nevertheless, its effects on human monocytes are still poorly understood. Thus,
      the present work investigated effects of ouabain in the activation and function
      of human adherent monocytes. Our results show that there is an increase in
      intracellular calcium levels already 5 minutes following monocyte treatment with
      10(-7) M of ouabain. Furthermore, monocytes expressed increased amounts of
      surface activation markers such as CD69, HLA-DR, CD86, and CD80 and also
      presented an augmented endocytic activity of dextran-FITC particles after 24
      hours of culture in the presence of ouabain. However, monocytes treated with
      ouabain did not have an increased stimulatory capacity in allogeneic mixed
      leukocyte reaction. Ouabain-treated monocytes produced higher levels of IL-1 beta
      and TNF- alpha as reported before. A novel observation was the fact that ouabain
      induced IL-10 and VEGF as well. Collectively, these results suggest that ouabain
      impacts monocyte activation and modulates monocyte functions, implying that this
      steroid could act as an immunomodulator of these cells.

PMID- 24904199
TI  - Prescribing practices in hospice patients with adult failure to thrive or
      debility.
AB  - OBJECTIVES: Despite being a common admitting diagnosis, there is very little
      published literature on medication management in hospice patients admitted with a
      diagnosis of failure to thrive or debility. The purpose of this study was to
      describe medication prescribing practices in hospice patients with either of
      these primary diagnoses by characterizing prescribed medications by name and by
      pharmaceutical class, and determining whether the patient or the hospice
      organization provided each medication. METHODS: A retrospective review of a
      patient information database compiled by a national hospice organization was
      conducted. Patients were included in this retrospective study if they were
      admitted to hospice care with a primary diagnosis of failure to thrive or
      debility, and if they were admitted on or after 1 January 2010, and discharged by
      death on or before 31 December 2010. RESULTS: Overall 293 patients and 6181
      medication entries were evaluated. The most commonly prescribed drugs were
      acetaminophen, lorazepam, morphine, atropine, prochlorperazine, haloperidol,
      docusate, aspirin, and bisacodyl. The most commonly prescribed pharmacological
      classes were opioid and non-opioid analgesics, anxiolytics, anticholinergics,
      antihypertensives, laxatives, antidepressants, and supplements. The hospice
      organization provided over 90% of prescriptions for analgesics, antipsychotics,
      anticholinergics, and anxiolytics, and these medications were discontinued before
      death in less than 5% of patients. CONCLUSION: Recognized clinical components of
      failure to thrive syndrome include cognitive impairment, malnutrition, and
      depression. The hospice organization provided 80% of antidepressants, but
      infrequently provided appetite stimulants and drugs treating dementia. The most
      commonly provided drugs were those used for symptoms associated with most end
      stage diseases.

PMID- 24904198
TI  - Protective effects of lipoxin A4 in testis injury following testicular torsion
      and detorsion in rats.
AB  - PURPOSE: To investigate the protective effects of lipoxin A4 (LXA4) in rat testis
      injury following testicular torsion/detorsion. METHODS: A rat testicular torsion
      model has been established as described. Rats were randomly divided into 6
      groups: sham group, torsion group, torsion/detorsion (T/D) group, and T/D plus
      LXA4-pretreated groups (3 subgroups). Rats in LXA4-pretreated groups received
      LXA4 injection (0.1, 1.0, and 10 MUg/kg body weight in LXA4-pretreated subgroups
      1-3, resp.) at a single dose 1 h before detorsion. Biochemical analysis,
      apoptosis assessment, and morphologic evaluation were carried out after
      orchiectomies. RESULTS: GPx and SOD levels significantly increased and MDA levels
      significantly reduced in LXA4-pretreated groups compared to T/D group. LXA4 also
      reverted IL-2 and TNF- alpha to basal levels and improved the expression of IL-4
      and IL-10 in LXA4-pretreated groups. Moreover, the expression of NF- kappa B was
      downregulated in LXA4-pretreated groups. LXA4 treatment also showed an improved
      testicular morphology and decreased apoptosis in testes. CONCLUSION: Lipoxin A4
      protects rats against testes injury after torsion/detorsion via modulation of
      cytokines, oxidative stress, and NF- kappa B activity.

PMID- 24904200
TI  - Use of Psychotropic Medications among Youth in Treatment Foster Care.
AB  - We describe the use of psychotropic medications among youth in treatment foster
      care (TFC). Data from 240 youth were coded to examine rates of medication use,
      including polypharmacy and an indicator of "questionable polypharmacy." Fifty
      nine percent of youth in TFC had taken a psychotropic medication within the past
      two months. Of the youth taking psychotropics, 61% took two or more and 22% met
      criteria for questionable polypharmacy. The majority of youth taking
      psychotropics also received psychosocial mental health services and were more
      likely to receive such services than youth not taking medication. Use of
      psychotropic medication use was not significantly related to demographic factors,
      maltreatment history, or custody. However, youth with more severe symptoms were
      more likely to be on medications and to be on multiple medications. Youth with
      "questionable polypharmacy" were less likely than other youth on multiple
      medications to have a recent visit to a psychiatrist.

PMID- 24904201
TI  - Using semantic web technologies to annotate and align microarray designs.
AB  - In this paper, we annotate and align two different gene expression microarray
      designs using the Genomic ELement Ontology (GELO). GELO is a new ontology that
      leverages an existing community resource, Sequence Ontology (SO), to create views
      of genomically-aligned data in a semantic web environment. We start the process
      by mapping array probes to genomic coordinates. The coordinates represent an
      implicit link between the probes and multiple genomic elements, such as genes,
      transcripts, miRNA, and repetitive elements, which are represented using concepts
      in SO. We then use the RDF Query Language (SPARQL) to create explicit links
      between the probes and the elements. We show how the approach allows us to easily
      determine the element coverage and genomic overlap of the two array designs. We
      believe that the method will ultimately be useful for integration of cancer data
      across multiple omic studies. The ontology and other materials described in this
      paper are available at http://krauthammerlab.med.yale.edu/wiki/Gelo. 

PMID- 24904202
TI  - Golimumab in unresponsive ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammation mainly affecting the colon
      mucosa. It predominantly occurs in younger patients. Until recently, the main
      goals in the treatment of UC were to temper the symptoms, such as diarrhea, pain,
      and weight loss, by using mesalazine and steroids. With newer medications, such
      as immunomodulators (thiopurines) and the biologics providing blockade of tumor
      necrosis factor (TNF), the goals of the therapy in UC have changed to long-term
      remission and mucosal healing. The first available anti-TNF therapy in UC
      included infusion therapy with infliximab every few weeks. In 2012,
      subcutaneously administered adalimumab gained approval for the treatment of UC in
      Germany. In patients with a mild disease, therapy with mesalazine, orally or
      topically, can be sufficient. In patients with moderate to severe disease,
      therapy with azathioprine or anti-TNF is often required to reach disease control;
      however, this is only efficient in about two-thirds of patients. Some patients
      either show no response or a lost response while on treatment. So, further
      medical options are warranted in the treatment of UC. With golimumab, a new
      approach in the treatment of mild to moderate UC recently became available in
      Germany and is a promising new option in the therapy regimen for patients with
      UC. 

PMID- 24904203
TI  - Importance of acute renal failure with ibuprofen.

PMID- 24904204
TI  - Transcutaneous electrical nerve stimulation in the treatment of patients with
      poststroke urinary incontinence.
AB  - PURPOSE: To investigate the therapeutic effect of transcutaneous electrical nerve
      stimulation (TENS) on poststroke urinary incontinence (UI). PATIENTS AND METHODS:
      Sixty-one patients with poststroke UI were enrolled at the Neurology Department
      in the Shanghai Tenth People's Hospital of Tongji University between January 2010
      January 2011 and were divided into treatment and control groups (n=32 and n=29,
      respectively). TENS was applied to the treatment group, while the control group
      received basic therapy. The therapeutic group completed the whole set of TENS
      therapy with a treatment frequency of 30 minutes once a day for 60 days. The
      positive electrode was placed on the second lumbar spinous process, and the
      negative electrodes were inside the middle and lower third of the junction
      between the posterior superior iliac spine and ischia node. The overactive
      bladder symptom score, Barthel Index, and urodynamics examination were estimated
      before and after therapy in both groups. RESULTS: The daily micturition,
      nocturia, urgent urination, and urge UI in the treatment group significantly
      improved compared to the control group (P<0.05). The patients in the treatment
      group were superior in the self-care ability of daily living and also had an
      advantage over the indexes on maximum cystometry volume, flow rate, and the
      pressure of detrusor in the end of the filling phase. CONCLUSION: TENS improved
      incontinence symptoms, enhanced the quality of life, and decreased adverse
      effects; hence, it is recommended in treating poststroke UI.

PMID- 24904205
TI  - Association between previously identified loci affecting telomere length and
      coronary heart disease (CHD) in Han Chinese population.
AB  - PURPOSE: To replicate previously confirmed telomere-length loci in a Chinese Han
      population with coronary heart disease (CHD), and investigate these loci and the
      possibility of and age at onset of CHD. PATIENTS AND METHODS: 1514 CHD patients
      and 2470 normal controls were recruited. Medical data including age, sex, body
      mass index, lipid profiles, history of hypertension, type 2 diabetes mellitus,
      and dyslipidemia were collected from all the participants. Seven previously
      identified single-nucleotide polymorphisms (SNPs) related to leucocyte telomere
      length were genotyped, including rs10936599 in TERC, rs2736100 in TERT, rs7675998
      in NAF1, rs9420907 in OBFC1, rs8105767 in ZNF208, rs755017 in RTEL1, and
      rs11125529 in ACYP2. RESULTS: No significant difference in genotype frequencies
      from the Hardy-Weinberg equilibrium test was noted for all tested SNPs both in
      the CHD patients and the normal controls. No polymorphism was observed for
      rs9420907, and AA genotype was noted in both the CHD patients and the controls.
      Neither the genotype nor the allele frequencies of rs2736100, rs8105767,
      rs11125529, and rs2967374 were significantly different between the CHD patients
      and the normal controls. For rs10936599 and rs755017, statistical difference was
      found for the allele frequency but not genotype. Distributions of genotype and
      allele were significantly different between the two groups for rs7675998. The
      odds ratio for carriers of CHD was 2.127 (95% confidence interval: 1.909-2.370)
      for the A allele of rs7675998. By one-way analysis of variance test, rs7675998
      was associated with the onset age of CHD. CHD patients with the AA genotype of
      rs7675998 had significantly lower onset age (P<0.05). CONCLUSION: In a Chinese
      Han population, NAF1 gene encoding proteins with known function in telomere
      biology may influence both the possibility of and the age at onset of CHD, as
      previously reported in European studies.

PMID- 24904206
TI  - Social embeddedness as a mechanism for linking social cohesion to well-being
      among older adults: moderating effect of gender.
AB  - BACKGROUND: The positive effect of social cohesion on well-being in older adults
      has been well documented. However, relatively few studies have attempted to
      understand the mechanisms by which social cohesion influences well-being. The
      main aim of the current study is to identify social pathways in which social
      cohesion may contribute to well-being. METHODS: The data for this study (taken
      from 1,880 older adults, aged 60 years and older) were drawn from a national
      survey conducted during 2008-2009. The survey employed a two-stage stratified
      sampling process for data collection. Structural equation modeling was used to
      test mediating and moderating analyses. RESULTS: The proposed model documented a
      good fit to the data (GFI =98; CFI =0.99; RMSEA =0.04). The findings from
      bootstrap analysis and the Sobel test revealed that the impact of social cohesion
      on well-being is significantly mediated by social embeddedness (Z=5.62; P<0.001).
      Finally, the results of a multigroup analysis test showed that social cohesion
      influences well-being through the social embeddedness mechanism somewhat
      differently for older men than women. CONCLUSION: The findings of this study, in
      addition to supporting the importance of neighborhood social cohesion for the
      well-being of older adults, also provide evidence that the impact of social
      cohesion towards well-being is mediated through the mechanism of social
      embeddedness.

PMID- 24904207
TI  - Effects of hypercapnia on peripheral vascular reactivity in elderly patients with
      acute exacerbation of chronic obstructive pulmonary disease.
AB  - Blood acid-base imbalance has important effects on vascular reactivity, which can
      be related to nitric oxide (NO) concentration and increased during hypercapnia.
      Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation
      of chronic obstructive pulmonary disease (COPD), a common medical condition in
      the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk
      indicator, allows assessment of endothelial-dependent vasodilation, which is to a
      certain extent mediated by NO. We investigated the effects of hypercapnia and
      acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD
      in 96 elderly patients with acute exacerbation of COPD. Patients underwent
      complete arterial blood gas analysis and FMD measurement before (phase 1) and
      after (phase 2) standard therapy for acute exacerbation of COPD and recovery.
      Significant differences between phase 1 and phase 2 were observed in the mean
      values of pH (7.38+/-0.03 versus 7.40+/-0.02, P<0.001), pO2 (59.6+/-4.9 mmHg
      versus 59.7+/-3.6 mmHg, P<0.001), pCO2 (59.3+/-8.63 mmHg versus 46.7+/-5.82 mmHg,
      P<0.001), FMD (10.0%+/-2.8% versus 8.28%+/-2.01%, P<0.001) and blood flow rate
      (1.5+/-0.3 m/s versus 1.5+/-0.3 m/s, P=0.001). FMD values were positively
      correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant
      correlation was also found between relative changes in FMD and pCO2 levels,
      passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline
      endothelium-dependent vasodilation as evaluated by FMD showed greater
      modification with regard to pCO2 changes (2.6+/-1.39 versus 1.59+/-1.4, P=0.012).
      In conclusion, endothelium-dependent vasodilation as evaluated by FMD was
      elevated during hypercapnia, and varied significantly according to pCO2 changes
      in patients with higher baseline levels, suggesting that vascular reactivity in
      acute COPD exacerbations in the elderly depends on integrity of the vascular
      endothelium.

PMID- 24904208
TI  - Validity and reliability of the Thai version of the Confusion Assessment Method
      for the Intensive Care Unit (CAM-ICU).
AB  - PURPOSE: The purpose of this study was to determine the validity and reliability
      of the Thai version of the Confusion Assessment Method for the Intensive Care
      Unit (CAM-ICU), when compared to the diagnoses made by delirium experts. PATIENTS
      AND METHODS: This was a cross-sectional study conducted in both surgical
      intensive care and subintensive care units in Thailand between February-June
      2011. Seventy patients aged 60 years or older who had been admitted to the units
      were enrolled into the study within the first 48 hours of admission. Each patient
      was randomly assessed as to whether they had delirium by a nurse using the Thai
      version of the CAM-ICU algorithm (Thai CAM-ICU) or by a delirium expert using the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision. RESULTS: The prevalence of delirium was found to be 18.6% (n=13) by the
      delirium experts. The sensitivity of the Thai CAM-ICU's algorithms was found to
      be 92.3% (95% confidence interval [CI] =64.0%-99.8%), while the specificity was
      94.7% (95% CI =85.4%-98.9%). The instrument displayed good interrater reliability
      (Cohen's kappa =0.81; 95% CI =0.64-0.99). The time taken to complete the Thai CAM
      ICU was 1 minute (interquatile range, 1-2 minutes). CONCLUSION: The Thai CAM-ICU
      demonstrated good validity, reliability, and ease of use when diagnosing delirium
      in a surgical intensive care unit setting. The use of this diagnostic tool should
      be encouraged for daily, routine use, so as to promote the early detection of
      delirium and its rapid treatment.

PMID- 24904209
TI  - One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted
      magnetic resonance imaging.
AB  - In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized
      using a one-pot solution phase method for detection of atherosclerosis by
      magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of
      its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs
      stable and water-dispersible. The DMNCs were 65.6+/-4.3 nm, had a narrow size
      distribution, and were superparamagnetic with a high magnetization value of 60.1
      emu/g. Further, they showed biocompatibility and high cellular uptake efficiency,
      as indicated by a strong interaction between dextran and macrophages. In vivo
      magnetic resonance imaging demonstrated the ability of DMNCs to act as an
      efficient magnetic resonance imaging contrast agent capable of targeted detection
      of atherosclerosis. In view of these findings, it is concluded that DMNCs can be
      used as magnetic resonance imaging contrast agents to detect inflammatory
      disease. 

PMID- 24904210
TI  - Osteogenic response of human mesenchymal stem cells to well-defined nanoscale
      topography in vitro.
AB  - BACKGROUND: Patterning medical devices at the nanoscale level enables the
      manipulation of cell behavior and tissue regeneration, with topographic features
      recognized as playing a significant role in the osseointegration of implantable
      devices. METHODS: In this study, we assessed the ability of titanium-coated
      hemisphere-like topographic nanostructures of different sizes (approximately 50,
      100, and 200 nm) to influence the morphology, proliferation, and osteogenic
      differentiation of human mesenchymal stem cells (hMSCs). RESULTS: We found that
      the proliferation and osteogenic differentiation of hMSCs was influenced by the
      size of the underlying structures, suggesting that size variations in topographic
      features at the nanoscale level, independently of chemistry, can be exploited to
      control hMSC behavior in a size-dependent fashion. CONCLUSION: Our studies
      demonstrate that colloidal lithography, in combination with coating technologies,
      can be exploited to investigate the cell response to well defined nanoscale
      topography and to develop next-generation surfaces that guide tissue regeneration
      and promote implant integration.

PMID- 24904211
TI  - Optimization and evaluation of a thermoresponsive ophthalmic in situ gel
      containing curcumin-loaded albumin nanoparticles.
AB  - This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ
      gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin
      nanoparticles were prepared via a desolvation method, and the gels were prepared
      via a cold method. The central composite design and response surface method was
      used to evaluate the effects of varying Pluronic F127 and Pluronic F68
      concentrations on the sol-gel transition temperature, which is an indicator of
      optimum formulations. The optimized formulation was a free-flowing liquid below
      30.9 degrees C that transformed into a semi-solid gel above 34.2 degrees C after
      dilution with simulated tear fluid. Results of the in vitro release and erosion
      behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release
      effects and that incorporation of albumin nanoparticles exerted minimal effects
      on the gel structure. In addition, in vivo ophthalmic experiments employing Cur
      BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation
      results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug
      delivery. The in vivo study also revealed that the formulation could
      significantly increase curcumin bioavailability in the aqueous humor. In
      conclusion, the optimized in situ gel formulation developed in this work has
      significant potential for ocular application.

PMID- 24904212
TI  - Iodinated oil-loaded, fluorescent mesoporous silica-coated iron oxide
      nanoparticles for magnetic resonance imaging/computed tomography/fluorescence
      trimodal imaging.
AB  - In this study, a novel magnetic resonance imaging (MRI)/computed tomography
      (CT)/fluorescence trifunctional probe was prepared by loading iodinated oil into
      fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles
      (i-fmSiO4@SPIONs). Fluorescent mesoporous silica-coated superparamagnetic iron
      oxide nanoparticles (fmSiO4@SPIONs) were prepared by growing fluorescent dye
      doped silica onto superparamagnetic iron oxide nanoparticles (SPIONs) directed by
      a cetyltrimethylammonium bromide template. As prepared, fmSiO4@SPIONs had a
      uniform size, a large surface area, and a large pore volume, which demonstrated
      high efficiency for iodinated oil loading. Iodinated oil loading did not change
      the sizes of fmSiO4@SPIONs, but they reduced the MRI T2 relaxivity (r2) markedly.
      I-fmSiO4@SPIONs were stable in their physical condition and did not demonstrate
      cytotoxic effects under the conditions investigated. In vitro studies indicated
      that the contrast enhancement of MRI and CT, and the fluorescence signal
      intensity of i-fmSiO4@SPION aqueous suspensions and macrophages, were intensified
      with increased i-fmSiO4@SPION concentrations in suspension and cell culture
      media. Moreover, for the in vivo study, the accumulation of i-fmSiO4@SPIONs in
      the liver could also be detected by MRI, CT, and fluorescence imaging. Our study
      demonstrated that i-fmSiO4@SPIONs had great potential for MRI/CT/fluorescence
      trimodal imaging. 

PMID- 24904214
TI  - Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of
      isolated porcine coronary arteries: role of nitric oxide and calcium.
AB  - BACKGROUND AND PURPOSE: Cinnamaldehyde, a major component of cinnamon, induces
      the generation of reactive oxygen species and exerts vasodilator and anticancer
      effects, but its short half-life limits its clinical use. The present experiments
      were designed to compare the acute relaxing properties of cinnamaldehyde with
      those of self-assembling polymer micelles either loaded with cinnamaldehyde or
      consisting of a polymeric prodrug [poly(cinnamaldehyde)] that incorporates the
      compound in its backbone. METHODS: Rings of porcine coronary arteries were
      contracted with the thromboxane A2 receptor agonist U46619 or 40 mM KCl, and
      changes in isometric tension were recorded. RESULTS: Cinnamaldehyde induced
      concentration-dependent but endothelium-independent, nitric oxide synthase (NOS)
      independent, cyclooxygenase-independent, soluble guanylyl cyclase (sGC)
      independent, calcium-activated potassium-independent, and TRPA1 channel
      independent relaxations. Cinnamaldehyde also inhibited the contractions induced
      by 40 mM KCl Ca(2+) reintroduction in 40 mM KCl Ca(2+)-free solution or by the
      Ca(2+) channel opener Bay K8644. Cinnamaldehyde-loaded control micelles induced
      complete, partly endothelium-dependent relaxations sensitive to catalase and
      inhibitors of NOS or sGC, but not cyclooxygenase or TRPA1, channels.
      Cinnamaldehyde-loaded micelles also inhibited contractions induced by 40 mM KCl
      Ca(2+) reintroduction or Bay K8644. Poly(cinnamaldehyde) micelles induced only
      partial, endothelium-dependent relaxations that were reduced by inhibitors of NOS
      or sGC and by catalase and the antioxidant tiron, but not by indomethacin or
      TRPA1 channel blockers. CONCLUSION: The present findings demonstrate that
      cinnamaldehyde-loaded and poly(cinnamaldehyde) micelles possess vasodilator
      properties, but that the mechanism underlying the relaxation that they cause
      differs from that of cinnamaldehyde, and thus could be used both to relieve
      coronary vasospasm and for therapeutic drug delivery.

PMID- 24904213
TI  - Nanomedicine for drug targeting: strategies beyond the enhanced permeability and
      retention effect.
AB  - The growing research interest in nanomedicine for the treatment of cancer and
      inflammatory-related pathologies is yielding encouraging results. Unfortunately,
      enthusiasm is tempered by the limited specificity of the enhanced permeability
      and retention effect. Factors such as lack of cellular specificity, low vascular
      density, and early release of active agents prior to reaching their target
      contribute to the limitations of the enhanced permeability and retention effect.
      However, improved nanomedicine designs are creating opportunities to overcome
      these problems. In this review, we present examples of the advances made in this
      field and endeavor to highlight the potential of these emerging technologies to
      improve targeting of nanomedicine to specific pathological cells and tissues. 

PMID- 24904216
TI  - Transparent, biocompatible nanostructured surfaces for cancer cell capture and
      culture.
AB  - Circulating tumor cells (CTCs) in the blood which have detached from both the
      primary tumor and any metastases may be considered as a "liquid biopsy" and are
      expected to replace tumor biopsies in the monitoring of treatment response and
      determining patient prognosis. Here, we introduce a facile and efficient CTC
      detection material made of hydroxyapatite/chitosan (HA/CTS), which is beneficial
      because of its transparency and excellent biological compatibility. Atomic force
      microscopy images show that the roughness of the HA/CTS nanofilm (HA/CTSNF)
      substrates can be controlled by changing the HA:CTS ratio. Enhanced local
      topographic interactions between nano-components on cancer cell membranes, and
      the antibody coated nanostructured substrate lead to improved CTC capture and
      separation. This remarkable nanostructured substrate has the potential for CTC
      culture in situ and merits further analysis. CTCs captured from artificial blood
      samples were observed in culture on HA/CTSNF substrates over a period of 14 days
      by using conventional staining methods (hematoxylin eosin and Wright's stain). We
      conclude that these substrates are multifunctional materials capable of isolating
      and culturing CTCs for subsequent studies. 

PMID- 24904217
TI  - Opioid-induced constipation in patients with chronic noncancer pain in the USA,
      Canada, Germany, and the UK: descriptive analysis of baseline patient-reported
      outcomes and retrospective chart review.
AB  - BACKGROUND: The characteristics of patients who suffer from noncancer pain and
      opioid-induced constipation are not well understood. METHODS: Cross-sectional
      patient survey and chart review data from the baseline assessment of an ongoing
      longitudinal study in the USA, Canada, Germany, and the UK were evaluated via
      descriptive statistics. Participants had confirmation of daily opioid therapy
      >=30 mg for >=4 weeks and self-reported opioid-induced constipation. Response to
      laxatives was defined by classifying participants into categories of laxative use
      and evaluating the prevalence of inadequate response to one laxative agent and
      two or more agents from at least two different laxative classes. Outcomes
      included the Patient Assessment of Constipation-Symptoms, Work Productivity and
      Activity Impairment Questionnaire-Specific Health Problem, EuroQOL 5 Dimensions,
      and Global Assessment of Treatment Benefit, Satisfaction, and Willingness to
      Continue. RESULTS: Patients reported a mean of 1.4 bowel movements not preceded
      by laxatives and 3.7 bowel movements with laxative use per week; 83% wanted at
      least one bowel movement per day. Most commonly reported on Patient Assessment of
      Constipation-Symptoms were straining/squeezing to pass bowel movements (83%),
      bowel movements too hard (75%), flatulence (69%), and bloating (69%). Eighty-four
      percent were taking natural or behavioral therapies; 60% were taking at least one
      over-the-counter laxative; and 19% were taking at least one prescription
      laxative. Prevalence of inadequate response to one laxative agent was 94%;
      inadequate response to two or more agents from at least two different laxative
      classes was 27%. Mean Work Productivity and Activity Impairment Questionnaire
      Specific Health Problem values for percent work time missed, percent impairment
      while working, and percent activity impairment were 9%, 32% (equivalent of 14
      hours of lost productivity per week), and 38%. Mean EuroQOL 5 Dimensions index
      and visual analog scale scores were 0.49 and 50.6, respectively. Forty-four
      percent reported being satisfied with their treatment for constipation.
      CONCLUSION: Patients treated with opioids for noncancer pain commonly endure
      constipation symptoms that limit their work productivity and overall health
      related quality of life while adhering to treatments that provide little relief.
      Further research is needed to identify more efficacious constipation therapies
      for this patient population.

PMID- 24904218
TI  - Comparison of the costs of nonoperative care to minimally invasive surgery for
      sacroiliac joint disruption and degenerative sacroiliitis in a United States
      commercial payer population: potential economic implications of a new minimally
      invasive technology.
AB  - INTRODUCTION: Low back pain is common and treatment costly with substantial lost
      productivity and lost wages in the working-age population. Chronic low back pain
      originating in the sacroiliac (SI) joint (15%-30% of cases) is commonly treated
      with nonoperative care, but new minimally invasive surgery (MIS) options are also
      effective in treating SI joint disruption. We assessed whether the higher initial
      MIS SI joint fusion procedure costs were offset by decreased nonoperative care
      costs from a US commercial payer perspective. METHODS: An economic model compared
      the costs of treating SI joint disruption with either MIS SI joint fusion or
      continued nonoperative care. Nonoperative care costs (diagnostic testing,
      treatment, follow-up, and retail pharmacy pain medication) were from a
      retrospective study of Truven Health MarketScan((r)) data. MIS fusion costs were
      based on the Premier's PerspectiveTM Comparative Database and professional fees
      on 2012 Medicare payment for Current Procedural Terminology code 27280. RESULTS:
      The cumulative 3-year (base-case analysis) and 5-year (sensitivity analysis)
      differentials in commercial insurance payments (cost of nonoperative care minus
      cost of MIS) were $14,545 and $6,137 per patient, respectively (2012 US dollars).
      Cost neutrality was achieved at 6 years; MIS costs accrued largely in year 1
      whereas nonoperative care costs accrued over time with 92% of up front MIS
      procedure costs offset by year 5. For patients with lumbar spinal fusion, cost
      neutrality was achieved in year 1. CONCLUSION: Cost offsets from new
      interventions for chronic conditions such as MIS SI joint fusion accrue over
      time. Higher initial procedure costs for MIS were largely offset by decreased
      nonoperative care costs over a 5-year time horizon. Optimizing effective resource
      use in both nonoperative and operative patients will facilitate cost-effective
      health care delivery. The impact of SI joint disruption on direct and indirect
      costs to commercial insurers, health plan beneficiaries, and employers warrants
      further consideration.

PMID- 24904219
TI  - Randomized controlled trial of a water-soluble nail lacquer based on
      hydroxypropyl-chitosan (HPCH), in the management of nail psoriasis.
AB  - BACKGROUND: Nail psoriasis occurs in up to 50% of patients affected by psoriasis,
      with a significant impact on quality of life that leads to a real clinical need
      for new therapeutic options. AIM: To confirm whether the strengthening and
      hardening properties of the hydroxypropyl-chitosan (HPCH) nail lacquer could
      improve the structure of the nail plates on psoriatic nails. MATERIALS AND
      METHODS: A randomized, double-blind, placebo controlled, parallel-group trial was
      carried out to evaluate the efficacy and tolerability of a hydrosoluble nail
      lacquer containing HPCH, Equisetum arvense, and methylsulfonylmethane on nail
      psoriasis. The test product or a placebo was applied once daily for 24 weeks to
      all fingernails. Efficacy assessments were performed on the target fingernail by
      means of the modified Nail Psoriasis Severity Index score. A cut-off score of 4
      was considered to define the clinical cure rate (ie, Cure <=4, Failure >4).
      RESULTS: After 24 weeks, the clinical cure rate showed the statistically
      significant superiority of the HPCH nail lacquer compared to placebo in both the
      intention-to-treat (Fisher's exact test, P=0.0445) and the per protocol
      population (Fisher's exact test, P=0.0437). This superiority was already present
      after 16 weeks of treatment. Moreover, the analysis of the modified Nail
      Psoriasis Severity Index-50 showed a statistically significant clinical
      improvement after 12 weeks of treatment in comparison to the results obtained
      after 8 weeks (Fisher's exact test, P<0.05). CONCLUSION: The trial showed that
      HPCH nail lacquer could be a new, valid, effective, and safe option for
      decreasing the signs of nail dystrophy in psoriatic patients.

PMID- 24904220
TI  - Profile of ustekinumab and its potential in patients with moderate-to-severe
      Crohn's disease.
AB  - The advent of anti-tumor necrosis factor (TNF)-alpha therapy has been a major
      advance in the medical management of Crohn's disease (CD). However, a significant
      proportion of patients with CD do not respond adequately to treatment with these
      agents. Primary and secondary nonresponse to anti-TNFalpha therapy represents a
      common clinical challenge, and highlights the need for the development of
      additional medication options for CD. The proinflammatory cytokines interleukin
      (IL)-12 and IL-23 are thought to play a key role in the pathogenesis of CD, and
      serve as a potential target for additional biologic therapies. Monoclonal
      antibodies targeting IL-12/23 have shown efficacy in animal models of colitis,
      and are currently being studied in Phase III clinical trials of CD. This review
      focuses on ustekinumab, a fully human immunoglobulin G1 monoclonal antibody,
      which blocks activity of IL-12 and IL-23 through binding the p40 subunit, and
      describes the current efficacy and safety data for ustekinumab in patients with
      CD. 

PMID- 24904221
TI  - Serum-derived bovine immunoglobulin/protein isolate: postulated mechanism of
      action for management of enteropathy.
AB  - The health and performance of the gastrointestinal tract is influenced by the
      interaction of a variety of factors, including diet, nutritional status,
      genetics, environment, stress, the intestinal microbiota, immune status, and gut
      barrier. Disruptions in one or more of these factors can lead to enteropathy or
      intestinal disorders that are known to occur in concert with certain disease
      states or conditions such as irritable bowel syndrome or human immunodeficiency
      virus (HIV) infection. Nutritional support in the form of a medical food along
      with current therapies could help manage the adverse effects of enteropathy,
      which include effects on nutrient digestion, absorption, and metabolism, as well
      as utilization of nutrients from foodstuffs. Numerous studies have demonstrated
      that oral administration of plasma- or serum-derived protein concentrates
      containing high levels of immunoglobulins can improve weight management,
      normalize gut barrier function, and reduce the severity of enteropathy in
      animals. Recent trials in humans provide preliminary evidence that a serum
      derived bovine immunoglobulin/protein isolate is safe and improves symptoms,
      nutritional status, and various biomarkers associated with enteropathy in
      patients with HIV infection or diarrhea-predominant irritable bowel syndrome.
      This review summarizes data from preclinical and clinical studies with
      immunoglobulin-containing plasma/serum protein concentrates, with a focus on the
      postulated mode of action of serum-derived bovine immunoglobulin/protein isolate
      for patients with enteropathy. 

PMID- 24904223
TI  - Presentation and management of docetaxel-related adverse effects in patients with
      breast cancer.
AB  - The taxane chemotherapeutic agent docetaxel has been utilized in the management
      of breast cancer in the adjuvant, neoadjuvant and metastatic setting. Although
      well tolerated by the majority of patients, docetaxel toxicity may limit the dose
      which can be administered. Adverse events include infusion reactions, febrile
      neutropenia, fatigue, fluid retention, pneumonitis, cutaneous and nail toxicity,
      epiphora and lacrimal duct stenosis, gastrointestinal complications, and
      neuropathies. In this review, we explore these complications and how they can be
      effectively managed to improve patient quality of life during and following
      docetaxel therapy. 

PMID- 24904222
TI  - Novel drugs that target the estrogen-related receptor alpha: their therapeutic
      potential in breast cancer.
AB  - THE INCIDENCE OF BREAST CANCER CONTINUES TO RISE: 1.7 million women were
      diagnosed with and 521,000 women died from breast cancer in 2012. This review
      considers first current treatment options: surgery; radiotherapy; and systemic
      endocrine, anti-biological, and cytotoxic therapies. Clinical management includes
      prevention, early detection by screening, treatment with curative intent,
      management of chronic disease, and palliative control of advanced breast cancer.
      Next, the potential of novel drugs that target DNA repair, growth factor
      dependence, intracellular and intercellular signal transduction, and cell cycle
      are considered. Estrogen-related receptor alpha has attracted attention as a
      therapeutic target in triple-negative breast cancers with de novo resistance to,
      and in breast cancers with acquired resistance to, endocrine therapies such as
      antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an
      orphan receptor and transcription factor. Its activity is regulated by
      coregulator proteins and posttranslational modification. It is an energy sensor
      that controls adaptation to energy demand and may facilitate glycolytic
      metabolism and mitochondrial oxidative respiration in breast cancer cells.
      Estrogen-related receptor alpha increases breast cancer cell migration,
      proliferation, and tumor development. It is expressed at high levels in estrogen
      receptor-negative tumors, and is proposed to activate estrogen-responsive genes
      in endocrine-resistant tumors. The structures and functions of the ligand-binding
      domains of estrogen receptor alpha and estrogen-related receptor alpha, their
      ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects
      of ligand agonists, antagonists, and inverse agonists on biological activity, are
      evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in
      preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology.
      The clinical settings in which these novel drugs might have utility in the
      management of advanced breast cancer, and biomarkers for stratification of
      patients likely to benefit, are discussed. Finally, the potential side effects of
      the novel drugs on metabolism, osteoporosis, osteo-metastasis, and cachexia are
      considered.

PMID- 24904225
TI  - Interns' perceived abuse during their undergraduate training at King Abdul Aziz
      University.
AB  - BACKGROUND AND OBJECTIVES: Abuse occurs in all workplaces, including the medical
      field. The aim of this study was to determine the prevalence of perceived abuse
      among medical students, the types of abuse experienced during medical training,
      the source of abuse, and the perceived barriers to reporting abuse. METHOD: This
      cross-sectional survey was conducted between September 2013 and January 2014
      among medical graduates of King Abdul Aziz University, Jeddah. The survey
      questionnaire was designed to gather information regarding the frequency with
      which participants perceived themselves to have experienced abuse, the type of
      abuse, the source of abuse, and the reasons for nonreporting of perceived abuse.
      Data were analyzed using the Statistical Package for the Social Sciences. RESULT:
      Of the 186 students enrolled in this study, 169 (90.9%) reported perceiving some
      form of abuse during medical school training. Perceived abuse was most often
      verbal (86.6%), although academic abuse (73.1%), sex discrimination (38.7%),
      racial or ethnic discrimination (29.0%), physical abuse (18.8%), religious
      discrimination (15.1%), and sexual harassment (8.6%) were also reported.
      Professors were most often cited as the sources of perceived abuse, followed by
      associate professors, demonstrators (or assistant teaching staff), and assistant
      professors. The Internal Medicine Department was the most frequently cited
      department where students perceived themselves to have experienced abuse. Only
      14.8% of the students reported the abuse to a third party. CONCLUSION: The self
      reported prevalence of medical student abuse at King Abdul Aziz University is
      high. A proper system for reporting abuse and for supporting victims of abuse
      should be set up, to promote a good learning environment.

PMID- 24904226
TI  - Stress management in dental students: a systematic review.
AB  - This study compared the effectiveness of stress management programs in dental
      education by systematic review of the literature. The number of studies
      concerning stress management programs for dental students is limited compared
      with studies discussing sources of stress. Several types of programs for stress
      management have been reported, and differ in their duration, content, and
      outcomes. Two main strategies have been used to help stressed students, ie,
      decreasing the number of stressors and increasing the ability to cope with
      stress. The first strategy includes several components, such as reducing fear of
      failure and workload pressure due to examinations and requirements. The second
      strategy includes coping techniques, such as deep breathing exercises. Although
      positive effects have been reported for most of the programs, these have mainly
      been evaluated using subjective self-report measures. There is a need for more
      research to identify the most effective stress management program. 

PMID- 24904224
TI  - A review of frovatriptan for the treatment of menstrual migraine.
AB  - The objective of this review is to provide an overview of menstrual migraine (MM)
      and of frovatriptan and to assess clinical trial data regarding the efficacy and
      safety of frovatriptan for the acute and short-term prophylaxis of MM. Randomized
      controlled trials comparing frovatriptan with placebo or a triptan comparator for
      the acute or prophylactic treatment of MM were selected for review. MM affects up
      to 60% of women with migraine. Compared with attacks at other times of the cycle,
      menstrual attacks are longer, more severe, less responsive to treatment, more
      likely to relapse, and more disabling than attacks at other times of the cycle.
      No drugs are licensed for acute treatment of MM; triptans are recommended for
      treatment of moderate to severe attacks for menstrual and nonmenstrual attacks.
      Perimenstrual prophylaxis is indicated for patients with predictable MM that does
      not respond to symptomatic treatment alone. Treatment is unlicensed, but options
      include triptans, nonsteroidal anti-inflammatory drugs, and hormone manipulation.
      Frovatriptan is distinctive from other triptans due to its long elimination half
      life of 26 hours, which confers a longer duration of action. Post hoc analyses
      from randomized trials of MM show similar pain relief and pain-free rates for
      frovatriptan compared with other triptans (2 hours pain-free: relative risk [RR]
      1.27, 95% confidence interval [CI] 0.91-1.76) but significantly lower relapse
      rates (24 hours sustained pain-free: RR 0.34, 95% CI 0.18-0.62). Data from
      randomized controlled trials show a significant reduction in risk of MM in women
      using frovatriptan 2.5 mg once daily (RR 1.56, 95% CI 1.31-1.86) or twice daily
      (RR 1.98, 95% CI 1.68-2.34) for perimenstrual prophylaxis compared with placebo.
      The twice daily dosing was more effective than once daily (RR 1.27, 95% CI 1.11
      1.46). These findings support the use of frovatriptan as a first-line acute
      treatment for MM and for perimenstrual prophylaxis. 

PMID- 24904227
TI  - Risk factors for long-term outcome of drug-eluting stenting in adults with early
      onset coronary artery disease.
AB  - OBJECTIVE: We lack data on the long-term outcome of drug-eluting stenting in
      patients with early-onset coronary artery disease (CAD). Here, we investigated
      the association of traditional risk factors and major adverse cardiovascular
      events (MACEs) after drug-eluting stenting in patients with CAD who were < 50
      years old. METHODS: We enrolled 437 consecutive CAD patients < 50 years old who
      underwent drug-eluting stenting and 132 subjects who were age- and sex-matched
      and angiographically shown to be disease free as controls. MACEs were analyzed in
      CAD patients for a median of 24 months [interquartile range 14-34 months].
      RESULTS: Male patients accounted for 90.4% of cases. As compared with controls,
      patients with early-onset CAD had higher body mass index and rates of smoking,
      family history of CAD, and diabetes and hypercholesterolemia. During the hospital
      stay, 1 patient died, and the incidence of MACEs was 1.1%. At the end of follow
      up, the overall death rate was 0.7%. MACEs were observed in 54 patients (12.4%).
      On Cox proportional hazard analyses, positive family history and diabetes were
      independent risk factors of MACEs (HR 2.61, 95% confidence interval 1.29-4.00, p
      = 0.002; and HR 2.48, 95% confidence interval 0.86-3.14, p = 0.004,
      respectively). CONCLUSIONS: Drug-eluting stenting is a reliable treatment for
      patients with early-onset CAD. Positive family history of CAD and diabetes are
      independent risk factors of adverse cardiovascular events in this subgroup of
      patients after drug-eluting stent implantation.

PMID- 24904228
TI  - Polymorphism of Nrf2, an antioxidative gene, is associated with blood pressure
      and cardiovascular mortality in hemodialysis patients.
AB  - OBJECTIVE: Nrf2 is a transcription factor that regulates the expression of
      antioxidant genes. This study aimed to investigate the association of Nrf2 gene
      single nucleotide polymorphisms (SNPs), rs35652124 (-653A/G) and rs6721961 (
      617C/A), with laboratory data and mortality in hemodialysis (HD) patients.
      METHODS: Blood samples were obtained from 216 HD patients (119 males and 97
      females; 60 diabetics and 156 non-diabetics) with mean age of 60.3+/-13.3 (SD)
      years, and mean HD duration of 9.10+/-8.28 years. Genotyping was performed using
      polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay.
      RESULTS: As for rs35652124, diastolic blood pressure (BP) was significantly high
      in total AA carriers. beta2-microglobulin was significantly low in male AA
      carriers. Systolic BP, diastolic BP and albumin were significantly high in female
      AA carriers. As for 6721961, systolic BP and diastolic BP were significantly high
      in female AA carriers. Cox proportional hazard analysis adjusted for age, HD
      duration, diabetes and Kt/V demonstrated that rs35652124 AA carriers showed
      higher cardiovascular mortality than (GG+GA) carriers. CONCLUSION: Nrf2 SNPs were
      associated with BP in Japanese HD patients. More notably, rs35652124 was
      associated with cardiovascular mortality in these patients.

PMID- 24904230
TI  - Cyanidin 3-O-glucoside reduces Helicobacter pylori VacA-induced cell death of
      gastric KATO III cells through inhibition of the SecA pathway.
AB  - Two key virulence factors of Helicobacter pylori are the secreted virulent
      proteins of vacuolating toxin A (VacA) and cytotoxin associated protein A (CagA)
      which lead to damages of gastric epithelial cells. We previously identified that
      the cyanidin 3-O-glucoside (C3G) inhibits the secretion of both VacA and CagA. In
      the current report, we show that C3G inhibits VacA secretion in a dose-dependent
      manner by inhibiting secretion system subunit protein A (SecA) synthesis. As SecA
      is involved in translocation of bacterial proteins, we predicted that inhibition
      of the SecA pathway by C3G should decrease H. pylori-induced cell death. To test
      this hypothesis, the human gastric cell line KATO III cells were co-cultured with
      H. pylori 60190 (VacA(+)/CagA(+)) and C3G. We found that C3G treatment caused a
      decrease in activation of the pro-apoptotic proteins caspase-3/-8 in H. pylori
      infected cells leading to a decrease in cell death. Our data suggest that
      consumption of foods containing anthocyanin may be beneficial in reducing cell
      damage due to H. pylori infection. 

PMID- 24904229
TI  - Paratyphoid fever: splicing the global analyses.
AB  - The incidence of enteric fever caused by Salmonella enterica serovar Paratyphi A
      (S. Paratyphi A) is increasing in many parts of the world. Although there is no
      major outbreak of paratyphoid fever in recent years, S. Paratyphi A infection
      still remains a public health problem in many tropical countries. Therefore,
      surveillance studies play an important role in monitoring infections and the
      emergence of multidrug resistance, especially in endemic countries such as India,
      Nepal, Pakistan and China. In China, enteric fever was caused predominantly by S.
      Paratyphi A rather than by Salmonella enterica serovar Typhi (S. Typhi).
      Sometimes, S. Paratyphi A infection can evolve into a carrier state which
      increases the risk of transmission for travellers. Hence, paratyphoid fever is
      usually classified as a "travel-associated" disease. To date, diagnosis of
      paratyphoid fever based on the clinical presentation is not satisfactory as it
      resembles other febrile illnesses, and could not be distinguished from S. Typhi
      infection. With the availability of Whole Genome Sequencing technology, the
      genomes of S. Paratyphi A could be studied in-depth and more specific targets for
      detection will be revealed. Hence, detection of S. Paratyphi A with Polymerase
      Chain Reaction (PCR) method appears to be a more reliable approach compared to
      the Widal test. On the other hand, due to increasing incidence of S. Paratyphi A
      infections worldwide, the need to produce a paratyphoid vaccine is essential and
      urgent. Hence various vaccine projects that involve clinical trials have been
      carried out. Overall, this review provides the insights of S. Paratyphi A,
      including the bacteriology, epidemiology, management and antibiotic
      susceptibility, diagnoses and vaccine development. 

PMID- 24904231
TI  - A novel catechol-O-methyltransferase variant associated with human disc
      degeneration.
AB  - BACKGROUND: Disc degeneration and its associated low back pain are a major health
      care concern causing disability with a prominent role in this country's medical,
      social and economic structure. Low back pain is devastating and influences the
      quality of life for millions. Low back pain lifetime prevalence approximates 80%
      with an estimated direct cost burden of $86 billion per year. Back pain patients
      incur higher costs, greater health care utilization, and greater work loss than
      patients without back pain. METHODS: Research was performed following approval of
      our Institutional Review Board. DNA was isolated, processed and amplified using
      routine techniques. Amplified DNA was hybridized to Affymetrix Genome-Wide Human
      SNP Arrays. Quality control and genotyping analysis were performed using
      Affymetrix Genotyping Console. The Birdseed v2 algorithm was used for genotyping
      analysis. 2589 SNPs were selected a priori to enter statistical analysis using
      lotistic regression in SAS. RESULTS: Our objective was to search for novel single
      nucleotide polymorphisms (SNPs) associated with disc degeneration. Four SNPs were
      found to have a significant relationship to disc degeneration; three are novel.
      Rs165656, a new SNP found to be associated with disc degeneration, was in
      catechol-O-methyltransferase (COMT), a gene with well-recognized pain
      involvement, especially in female subjects (p=0.01). Analysis confirmed the
      previously association between COMT SNP rs4633 and disc degeneration. We also
      report two novel disc degeneration-related SNPs (rs2095019 and rs470859) located
      in intergenic regions upstream to thrombospondin 2. CONCLUSIONS: Findings
      contribute to the challenging field of disc degeneration and pain, and are
      important in light of the high clinical relevance of low back pain and the need
      for improved understanding of its fundamental basis.

PMID- 24904232
TI  - Cyclin A1 is expressed in mouse ovary.
AB  - Cyclin A1 belongs to the type-A cyclins and participates in cell cycle
      regulation. Since its discovery, cyclin A1 has been shown mostly in testis. It
      plays important roles in spermatogenesis. However, there were also reports on
      ovary expression of cyclin A1. Therefore, we intended to revisit the expression
      of cyclin A1 in mouse ovary. Our study showed that cyclin A1 was expressed at the
      mRNA level and the protein level in mouse ovary. Tissue staining revealed that
      cyclin A1 was expressed in maturating oocytes. With the recent data on the
      functions of cyclins in somatic and stem cells, we also discussed the
      possibilities of further studies of cyclin A1 in mouse oocytes and perhaps in the
      oogonial stem cells. Our findings not only add to the supportive evidence of
      cyclin A1 expression in oocytes, but also may promote more interest in exploring
      cyclin A1 functions in ovary. 

PMID- 24904233
TI  - Cardiac arrest is a predictor of difficult tracheal intubation independent of
      operator experience in hospitalized patients.
AB  - BACKGROUND: Placement of advanced airways has been associated with worsened
      neurologic outcome in survivors of out-of-hospital cardiac arrest. These findings
      have been attributed to factors such as inexperienced operators, prolonged
      intubation times and other airway related complications. As an initial step to
      examine outcomes of advanced airway placement during in-hospital cardiac arrest
      (IHCA), where immediate assistance and experienced operators are continuously
      available, we examined whether cardiopulmonary resuscitation efforts affect
      intubation difficulty. Additionally, we examined whether or not the use of
      videolaryngoscopy increases the odds of first attempt intubation success compared
      with traditional direct laryngoscopy. METHODS: The study setting is a large urban
      university-affiliated teaching hospital where experienced airway managers are
      available to perform emergent intubation for any indication in any out-of-the
      operating room location 24 hours a day, 7 days-a-week, 365 days-a-year.
      Intubations occurring in all adults >18 years-of-age who required emergent
      tracheal intubation outside of the operating room between January 1, 2008 and
      December 31, 2012 were examined retrospectively. Multivariate logistic regression
      was used to estimate the odds of difficult intubation during IHCA compared to
      other emergent non-IHCA indications with adjustment for a priori defined
      potential confounders (body mass index, operator experience, use of
      videolaryngoscopy versus direct laryngoscopy, and age). RESULTS: In adjusted
      analyses, the odds of difficult intubation were higher when taking place during
      IHCA (OR=2.63; 95% CI 1.1-6.3, p=0.03) compared to other emergent indications.
      Use of video versus direct laryngoscopy for initial intubation attempts during
      IHCA, however, did not improve the odds of success (adjusted OR = 0.71; 95% CI
      0.35-1.43, p = 0.33). CONCLUSIONS: Difficult intubation is more likely when
      intubation takes place during IHCA compared to other emergent indications, even
      when experienced operators are available. Under these conditions, direct
      laryngoscopy (versus videolaryngoscopy) remains a reasonable first choice
      intubation technique.

PMID- 24904234
TI  - TIP peptide inhalation in experimental acute lung injury: effect of repetitive
      dosage and different synthetic variants.
AB  - BACKGROUND: Inhalation of TIP peptides that mimic the lectin-like domain of TNF
      alpha is a novel approach to attenuate pulmonary oedema on the threshold to
      clinical application. A placebo-controlled porcine model of acute respiratory
      distress syndrome (ARDS) demonstrated a reduced thermodilution-derived
      extravascular lung water index (EVLWI) and improved gas exchange through TIP
      peptide inhalation within three hours. Based on these findings, the present study
      compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two
      alternate peptide versions (TIP-A, TIP-B). METHODS: Following animal care
      committee approval ARDS was induced by bronchoalveolar lavage followed by
      injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group
      setting compared the single-dosed peptide variants TIP-A and TIP-B as well as
      single versus repetitive inhalation of TIP-A (n = 7 per group). Over two three
      hour intervals parameters of gas exchange, transpulmonary thermodilution,
      calculated alveolar fluid clearance, and ventilation/perfusion-distribution were
      assessed. Post-mortem measurements included pulmonary wet/dry ratio and
      haemorrhage/congestion scoring. RESULTS: The repetitive TIP-A inhalation led to a
      significantly lower wet/dry ratio than a single dose and a small but
      significantly lower EVLWI. However, EVLWI changes over time and the derived
      alveolar fluid clearance did not differ significantly. The comparison of TIP-A
      and B showed no relevant differences. Gas exchange and ventilation/perfusion
      distribution significantly improved in all groups without intergroup differences.
      No differences were found in haemorrhage/congestion scoring. CONCLUSIONS: In
      comparison to a single application the repetitive inhalation of a TIP peptide in
      three-hour intervals may lead to a small additional reduction the lung water
      content. Two alternate TIP peptide versions showed interchangeable
      characteristics.

PMID- 24904235
TI  - Patients' experiences of lifestyle discussions based on motivational
      interviewing: a qualitative study.
AB  - BACKGROUND: According to World Health Organization about 75% of cardiovascular
      diseases and type 2 diabetes and 40% of all cases of cancer could be prevented if
      the risk factors tobacco use, unhealthy diets, physical inactivity and harmful
      use of alcohol could be eliminated. Patients often need help in monitoring
      themselves to make the proper lifestyle changes and it is important that adequate
      support is provided to enable the patients to take control over their health.
      Motivational interviewing is a framework that can help to facilitate this
      movement. The aim of this study was to describe how patients in primary health
      care settings experience lifestyle discussions based on motivational
      interviewing. METHODS: This study has a descriptive design and qualitative
      content analysis was used as the method. Sixteen patients who had each visited a
      registered nurse for lifestyle discussions were interviewed. RESULTS: The results
      show that the lifestyle discussions could enable self-determination in the
      process of lifestyle change but that certain conditions were required. Mutual
      interaction between the patient and the nurse that contributes to a sense of well
      being in the patients was a necessary condition for the lifestyle discussion to
      be helpful. When the discussion resulted in a new way of thinking about lifestyle
      and when patient initiative was encouraged, the discussion could contribute to
      change. The patient's free will to make a lifestyle change and the nurse's
      sensitivity in the discussions created fertile soil for change. CONCLUSIONS: This
      study focuses on MI-based discussions, and the result shows that a subset of
      patients, who self-reported that they are motivated and aware of their role in
      making lifestyle changes, appreciate these strategies. However, it is not known
      whether discussions would be experienced in the same way if RNs used another
      method or if patients who were less motivated, engaged, or aware of their role in
      making lifestyle changes were interviewed.

PMID- 24904236
TI  - Green Tea Extract (GTE) improves differentiation in human osteoblasts during
      oxidative stress.
AB  - BACKGROUND: Oxidative stress is involved in the pathogenesis of bone diseases
      such as osteoporosis, which has a high coincidence with fractures in elderly.
      Several studies showed positive effects of herbal bioactive substances on
      oxidative stress. This study analyses the effect of green tea extract (GTE)
      Sunphenon 90LB on primary human osteoblasts differentiation and viability during
      H2O2-induced oxidative stress. Moreover, it was analyzed, whether GTE acts during
      the HO-1 signaling pathway. METHODS: Human osteoblasts were isolated from femoral
      heads of patients undergoing total hip replacement. Beneficial effects of GTE on
      osteoblasts were examined in a dose- and time-dependent manner. Furthermore, GTE
      was given before, simultaneous with and after induction of oxidative stress with
      1 mM H2O2 to simulate prophylactic, acute and therapeutic use, respectively. Cell
      damage was measured by LDH leakage and cell viability by MTT assay. Flow
      cytometry was applied to measure formation of Reactive Oxygen Species by using
      2'7'-dichlorofluorescein-diacetate. The formation of Extracellular Matrix after
      differentiation with GTE supplementation during oxidative stress was visualized
      with von Kossa and Alizarin Red staining. Last one was additionally
      photometrically quantified. To assess the effects of H2O2 and GTE on the
      osteogenic genes, RT-PCR was performed. To evaluate the intramolecular influence
      of GTE after the stimulation the protein levels of HO-1 were analyzed. RESULTS:
      Stimulation of primary human osteoblasts with low doses of GTE during oxidative
      stress over 21 days improved mineralization. Furthermore, GTE supplementation in
      combination with H2O2 leads to a higher gene expression of osteocalcin and
      collagen1alpha1 during osteoblasts differentiation. Both are important for bone
      quality. Pre-incubation, co-incubation and post-incubation of osteoblasts with
      high doses of GTE protect the osteoblasts against acute oxidative stress as shown
      by increased cell viability, decreased LDH leakage, and reduced production of
      intracellular free radicals. Functional analysis revealed an increased HO-1
      protein synthesis after stimulation with GTE. CONCLUSIONS: Incubation of human
      primary osteoblasts with GTE significantly reduces oxidative stress and improves
      cell viability. GTE also has a beneficial effect on ECM production which might
      improve the bone quality. Our findings suggest that dietary supplementation of
      GTE might reduce inflammatory events in bone-associated diseases such as
      osteoporosis.

PMID- 24904237
TI  - Effect of remote ischemic post-conditioning on systemic inflammatory response and
      survival rate in lipopolysaccharide-induced systemic inflammation model.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) and postconditioning (RpostC)
      have protective effects on ischemia and reperfusion injury. The effects have been
      reported to activate heme oxygenase-1 (HO-1) and attenuate nuclear factor kappa B
      (NF-kappaB) and subsequently reduce systemic inflammation. Ischemic
      preconditioning prevented inflammatory responses by modulating HO-1 expression in
      endotoxic shock model. Therefore, we investigated whether RpostC could have
      protective effects on lipopolysaccharide (LPS)-induced systemic inflammation.
      METHODS: The LPS-induced sepsis mice received LPS (20 mg/kg) intraperitoneally.
      Remote ischemic conditioning was induced with three 10-min ischemia/10-min
      reperfusion cycles of the right hind limbs using tourniquet before LPS injection
      (RIPC) or after LPS injection (RpostC). The effects of RIPC and RpostC were
      examined for the survival rate, serum cytokines, NF-kappaB, HO-1 and liver
      pathology in the LPS injected mice. RESULTS: Survival rate within 120 hours
      significantly increased in the LPS injected and remote ischemic conditioned mice
      than in LPS only injected mice (60-65% vs 5%, respectively, p < 0.01). Tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin
      6 (IL-6) increased markedly in the LPS only injected mice, however, remote
      ischemic conditioning suppressed the changes (p < 0.05). Interleukin-10 (IL-10)
      level was significantly higher in the LPS injected and RpostC treated mice than
      in the LPS only injected mice (p = 0.014). NF-kappaB activation was significantly
      attenuated (p < 0.05) and HO-1 levels were substantially higher in the LPS
      injected and remote ischemic conditioned mice than in the LPS only injected mice.
      Neutrophil infiltration was significantly attenuated in the LPS injected and
      remote ischemic conditioned mice than in the only LPS injected mice (p < 0.05).
      CONCLUSIONS: RpostC attenuated inflammatory responses and improved survival
      outcomes of mice with LPS-induced systemic inflammation. The mechanism may be
      caused by modifying NF-kappaB mediated expression of cytokines.

PMID- 24904238
TI  - Protein phosphorylation differs significantly among ontogenetic phases in Malus
      seedlings.
AB  - BACKGROUND: Although protein phosphorylation is an important post-translational
      modification affecting protein function and metabolism, dynamic changes in this
      process during ontogenesis remain unexplored in woody angiosperms. METHODS:
      Phosphorylated proteins from leaves of three apple seedlings at juvenile, adult
      vegetative and reproductive stages were extracted and subjected to alkaline
      phosphatase pre-treatment. After separating the proteins by two-dimensional gel
      electrophoresis and phosphoprotein-specific Pro-Q Diamond staining,
      differentially expressed phosphoproteins were identified by MALDI-TOF-TOF mass
      spectrometry. RESULTS: A total of 107 phosphorylated protein spots on nine gels
      (three ontogenetic phases * three seedlings) were identified by MALDI-TOF-TOF
      mass spectrometry. The 55 spots of ribulose-1, 5-bisphosphate
      carboxylase/oxygenase (Rubisco) large-chain fragments varied significantly in
      protein abundance and degree of phosphorylation among ontogenetic phases.
      Abundances of the 27 spots corresponding to Rubisco activase declined between
      juvenile and reproductive phases. More extensively, phosphorylated beta-tubulin
      chain spots with lower isoelectric points were most abundant during juvenile and
      adult vegetative phases. CONCLUSIONS: Protein phosphorylation varied
      significantly during vegetative phase change and floral transition in apple
      seedlings. Most of the observed changes were consistent among seedlings and
      between hybrid populations.

PMID- 24904239
TI  - Detecting type 2 diabetes and prediabetes among asymptomatic adults in the United
      States: modeling American Diabetes Association versus US Preventive Services Task
      Force diabetes screening guidelines.
AB  - BACKGROUND: Screening to detect prediabetes and diabetes enables early prevention
      and intervention. This study describes the number and characteristics of
      asymptomatic, undiagnosed adults in the United States who could be detected with
      prediabetes and type 2 diabetes using the American Diabetes Association (ADA)
      guidelines compared to the United States Preventive Services Task Force (USPSTF)
      guidelines. METHODS: We developed predictive models for undiagnosed diabetes and
      prediabetes using polytomous logistic regression from data on risk factors in the
      2003-2010 National Health and Nutrition Examination Survey (n = 19,056). We
      applied these predictive models to the 2010 Medical Expenditure Panel Survey,
      which contains health care use data, to generate probabilities of undiagnosed
      diabetes and undetected prediabetes for each adult. We summed individual
      probabilities to estimate the number of adults who would be detected with
      prediabetes and/or type 2 diabetes if screened under ADA or USPSTF guidelines. We
      analyzed health care use patterns of people at high risk for diabetes. RESULTS:
      In 2010, 59.1 million adults met the USPSTF screening criteria including 24.4
      million people with undetected prediabetes and 3.7 million people with
      undiagnosed diabetes. In comparison, among the 86.3 million people who met the
      ADA screening criteria, there were 33.9 million with undetected prediabetes and
      4.6 million with undiagnosed type 2 diabetes. The ADA guidelines detected 38.9%
      more cases of prediabetes and 24.3% more cases of type 2 diabetes compared to the
      USPSTF guidelines. Subgroup analysis showed that ADA guidelines would detect 78%
      more cases of diabetes among the age 54 and younger population, in 40% more
      blacks, and in more than twice as many Hispanics than USPSTF guidelines. Only 58%
      of adults meeting ADA guidelines and 70% meeting USPSTF guidelines had >= 1
      primary care office visit in 2010. CONCLUSIONS: Compared to USPSTF guidelines,
      ADA guidelines would screen more people and detect more cases of both prediabetes
      and type 2 diabetes, though a substantial percentage of patients with undetected
      cases had no contact with a primary care provider in 2010. Addressing the problem
      of large numbers of undetected prediabetes and type 2 diabetes cases will require
      new strategies for screening.

PMID- 24904240
TI  - Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with
      juvenile idiopathic arthritis.
AB  - BACKGROUND: There are controversies regarding the accuracy of the tuberculin skin
      test (TST) and methods based on the production of interferon gamma by sensitized
      T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics
      and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T.
      SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing
      methotrexate, the correlation between both and the sensitivity and specificity of
      T. SPOT.TB. METHODS: This is an observational prospective longitudinal study in
      which children and adolescents with JIA undergoing methotrexate therapy were
      assessed for clinical and epidemiological data for LTBI, in addition to
      performing TST and T. SPOT.TB at baseline and after 3 and 12months. RESULTS:
      There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the
      incidence after initiation of immunosuppressions 26.3% and the prevalence at the
      end of the study 41.6%. Epidemiological history positive for TB showed a relative
      risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB
      but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a
      sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No
      patient developed TB disease at a mean follow-up of 47months. CONCLUSIONS: We
      found a high prevalence of ILTB that doubled with immunosuppression and that
      epidemiological history was an important relative risk. T. SPOT.TB showed low
      sensitivity and high specificity, and no superiority over TST. There was low
      agreement and little influence of immunosuppression on the results of both tests.

PMID- 24904241
TI  - mmeta: An R Package for Multivariate Meta-Analysis.
AB  - This paper describes the core features of the R package mmeta, whichimplements
      the exact posterior inference of odds ratio, relative risk, and risk difference
      given either a single 2 * 2 table or multiple 2 * 2 tables when the risks within
      the same study are independent or correlated.

PMID- 24904242
TI  - Connecting heterogeneous single slip to diffraction peak evolution in high-energy
      monochromatic X-ray experiments.
AB  - A forward modeling diffraction framework is introduced and employed to identify
      slip system activity in high-energy diffraction microscopy (HEDM) experiments. In
      the framework, diffraction simulations are conducted on virtual mosaic crystals
      with orientation gradients consistent with Nye's model of heterogeneous single
      slip. Simulated diffraction peaks are then compared against experimental
      measurements to identify slip system activity. Simulation results compared
      against diffraction data measured in situ from a silicon single-crystal specimen
      plastically deformed under single-slip conditions indicate that slip system
      activity can be identified during HEDM experiments.

PMID- 24904243
TI  - Stoichiometries and affinities of interacting proteins from concentration series
      of solution scattering data: decomposition by least squares and quadratic
      optimization.
AB  - In studying interacting proteins, complementary insights are provided by
      analyzing both the association model (the stoichiometry and affinity constants of
      the intermediate and final complexes) and the quaternary structure of the
      resulting complexes. Many current methods for analyzing protein interactions
      either give a binary answer to the question of association and no information
      about quaternary structure or at best provide only part of the complete picture.
      Presented here is a method to extract both types of information from X-ray or
      neutron scattering data for a series of equilibrium mixtures containing the
      initial components at different concentrations. The method determines the
      association pathway and constants, along with the scattering curves of the
      individual members of the mixture, so as to best explain the scattering data for
      the mixtures. The derived curves then enable reconstruction of the intermediate
      and final complexes. Using simulated solution scattering data for four hetero
      oligomeric complexes with different structures, molecular weights and association
      models, it is demonstrated that this method accurately determines the simulated
      association model and scattering profiles for the initial components and
      complexes. Recognizing that experimental mixtures contain static contaminants and
      nonspecific complexes with the lowest affinities (inter-particle interference) as
      well as the desired specific complex(es), a new analytical method is also
      employed to extend this approach to evaluating the association models and
      scattering curves in the presence of static contaminants, testing both a
      nonparticipating monomer and a large homo-oligomeric aggregate. It is
      demonstrated that the method is robust to both random noise and systematic noise
      from such contaminants, and the treatment of nonspecific complexes is discussed.
      Finally, it is shown that this method is applicable over a large range of weak
      association constants typical of specific but transient protein-protein
      complexes.

PMID- 24904244
TI  - An improved method for calibrating time-of-flight Laue single-crystal neutron
      diffractometers.
AB  - A robust and comprehensive method for determining the orientation matrix of a
      single-crystal sample using the neutron Laue time-of-flight (TOF) technique is
      described. The new method enables the measurement of the unit-cell parameters
      with an uncertainty in the range 0.015-0.06%, depending upon the crystal symmetry
      and the number of reflections measured. The improved technique also facilitates
      the location and integration of weak reflections, which are often more difficult
      to discern amongst the increased background at higher energies. The technique
      uses a mathematical model of the relative positions of all the detector pixels of
      the instrument, together with a methodology that establishes a reproducible
      reference frame and a method for determining the parameters of the instrument
      detector model. Since all neutron TOF instruments require precise detector
      calibration for their effective use, it is possible that the method described
      here may be of use on other instruments where the detector calibration cannot be
      determined by other means.

PMID- 24904245
TI  - Magnetic field dependent small-angle neutron scattering on a Co nanorod array:
      evidence for intraparticle spin misalignment.
AB  - The structural and magnetic properties of a cobalt nanorod array have been
      studied by means of magnetic field dependent small-angle neutron scattering
      (SANS). Measurement of the unpolarized SANS cross section dSigma/dOmega of the
      saturated sample in the two scattering geometries where the applied magnetic
      field H is either perpendicular or parallel to the wavevector ki of the incoming
      neutron beam allows one to separate nuclear from magnetic SANS, without employing
      the usual sector-averaging procedure. The analysis of the SANS data in the
      saturated state provides structural parameters (rod radius and centre-to-centre
      distance) that are in good agreement with results from electron microscopy.
      Between saturation and the coercive field, a strong field dependence of
      dSigma/dOmega is observed (in both geometries), which cannot be explained using
      the conventional expression of the magnetic SANS cross section of magnetic
      nanoparticles in a homogeneous nonmagnetic matrix. The origin of the strong field
      dependence of dSigma/dOmega is believed to be related to intradomain spin
      misalignment, due to magnetocrystalline and magnetoelastic anisotropies and
      magnetostatic stray fields.

PMID- 24904246
TI  - Cheetah: software for high-throughput reduction and analysis of serial
      femtosecond X-ray diffraction data.
AB  - The emerging technique of serial X-ray diffraction, in which diffraction data are
      collected from samples flowing across a pulsed X-ray source at repetition rates
      of 100 Hz or higher, has necessitated the development of new software in order to
      handle the large data volumes produced. Sorting of data according to different
      criteria and rapid filtering of events to retain only diffraction patterns of
      interest results in significant reductions in data volume, thereby simplifying
      subsequent data analysis and management tasks. Meanwhile the generation of
      reduced data in the form of virtual powder patterns, radial stacks, histograms
      and other meta data creates data set summaries for analysis and overall
      experiment evaluation. Rapid data reduction early in the analysis pipeline is
      proving to be an essential first step in serial imaging experiments, prompting
      the authors to make the tool described in this article available to the general
      community. Originally developed for experiments at X-ray free-electron lasers,
      the software is based on a modular facility-independent library to promote
      portability between different experiments and is available under version 3 or
      later of the GNU General Public License.

PMID- 24904247
TI  - GENFIT: software for the analysis of small-angle X-ray and neutron scattering
      data of macro-molecules in solution.
AB  - Many research topics in the fields of condensed matter and the life sciences are
      based on small-angle X-ray and neutron scattering techniques. With the current
      rapid progress in source brilliance and detector technology, high data fluxes of
      ever-increasing quality are produced. In order to exploit such a huge quantity of
      data and richness of information, wider and more sophisticated approaches to data
      analysis are needed. Presented here is GENFIT, a new software tool able to fit
      small-angle scattering data of randomly oriented macromolecular or nanosized
      systems according to a wide list of models, including form and structure factors.
      Batches of curves can be analysed simultaneously in terms of common fitting
      parameters or by expressing the model parameters via physical or phenomenological
      link functions. The models can also be combined, enabling the user to describe
      complex heterogeneous systems.

PMID- 24904248
TI  - A suite of software for processing MicroED data of extremely small protein
      crystals.
AB  - Electron diffraction of extremely small three-dimensional crystals (MicroED)
      allows for structure determination from crystals orders of magnitude smaller than
      those used for X-ray crystallography. MicroED patterns, which are collected in a
      transmission electron microscope, were initially not amenable to indexing and
      intensity extraction by standard software, which necessitated the development of
      a suite of programs for data processing. The MicroED suite was developed to
      accomplish the tasks of unit-cell determination, indexing, background
      subtraction, intensity measurement and merging, resulting in data that can be
      carried forward to molecular replacement and structure determination. This ad hoc
      solution has been modified for more general use to provide a means for processing
      MicroED data until the technique can be fully implemented into existing
      crystallographic software packages. The suite is written in Python and the source
      code is available under a GNU General Public License.

PMID- 24904250
TI  - A new view on crystal harvesting.
AB  - X-ray crystallography typically requires the mounting of crystals, which can make
      the sample difficult to manipulate when it is small and the microscope objective
      is close to the crystallization plate. By simply moving the objective to the
      bottom of a clear crystallization plate (inverting the normal view), crystals
      were able to be manipulated and harvested from wells having a 0.9 mm diameter and
      5.0 mm depth. The mounting system enabled the structural solution of the 187
      amino acid N-terminal domain of Saccharomyces cerevisiae glutaminyl-tRNA
      synthetase from crystals that appeared during high-throughput screening but
      proved recalcitrant to scale-up and optimization. While not a general mounting
      solution, the simple expedient of removing the objective lens from the area where
      manipulation and harvesting occur greatly facilitates the manual, or even
      automated, process.

PMID- 24904249
TI  - Using a commodity high-definition television for collaborative structural
      biology.
AB  - Visualization of protein structures using stereoscopic systems is frequently
      needed by structural biologists working to understand a protein's structure
      function relationships. Often several scientists are working as a team and need
      simultaneous interaction with each other and the graphics representations. Most
      existing molecular visualization tools support single-user tasks, which are not
      suitable for a collaborative group. Expensive caves, domes or geowalls have been
      developed, but the availability and low cost of high-definition televisions
      (HDTVs) and game controllers in the commodity entertainment market provide an
      economically attractive option to achieve a collaborative environment. This paper
      describes a low-cost environment, using standard consumer game controllers and
      commercially available stereoscopic HDTV monitors with appropriate signal
      converters for structural biology collaborations employing existing binary
      distributions of commonly used software packages like Coot, PyMOL, Chimera, VMD,
      O, Olex2 and others.

PMID- 24904251
TI  - Closed-loop control of spinal cord stimulation to restore hand function after
      paralysis.
AB  - As yet, no cure exists for upper-limb paralysis resulting from the damage to
      motor pathways after spinal cord injury or stroke. Recently, neural activity from
      the motor cortex of paralyzed individuals has been used to control the movements
      of a robot arm but restoring function to patients' actual limbs remains a
      considerable challenge. Previously we have shown that electrical stimulation of
      the cervical spinal cord in anesthetized monkeys can elicit functional upper-limb
      movements like reaching and grasping. Here we show that stimulation can be
      controlled using cortical activity in awake animals to bypass disruption of the
      corticospinal system, restoring their ability to perform a simple upper-limb
      task. Monkeys were trained to grasp and pull a spring-loaded handle. After
      temporary paralysis of the hand was induced by reversible inactivation of primary
      motor cortex using muscimol, grasp-related single-unit activity from the ventral
      premotor cortex was converted into stimulation patterns delivered in real-time to
      the cervical spinal gray matter. During periods of closed-loop stimulation, task
      modulated electromyogram, movement amplitude, and task success rate were improved
      relative to interleaved control periods without stimulation. In some sessions,
      single motor unit activity from weakly active muscles was also used successfully
      to control stimulation. These results are the first use of a neural prosthesis to
      improve the hand function of primates after motor cortex disruption, and
      demonstrate the potential for closed-loop cortical control of spinal cord
      stimulation to reanimate paralyzed limbs. 

PMID- 24904252
TI  - Learning to maximize reward rate: a model based on semi-Markov decision
      processes.
AB  - WHEN ANIMALS HAVE TO MAKE A NUMBER OF DECISIONS DURING A LIMITED TIME INTERVAL,
      THEY FACE A FUNDAMENTAL PROBLEM: how much time they should spend on each decision
      in order to achieve the maximum possible total outcome. Deliberating more on one
      decision usually leads to more outcome but less time will remain for other
      decisions. In the framework of sequential sampling models, the question is how
      animals learn to set their decision threshold such that the total expected
      outcome achieved during a limited time is maximized. The aim of this paper is to
      provide a theoretical framework for answering this question. To this end, we
      consider an experimental design in which each trial can come from one of the
      several possible "conditions." A condition specifies the difficulty of the trial,
      the reward, the penalty and so on. We show that to maximize the expected reward
      during a limited time, the subject should set a separate value of decision
      threshold for each condition. We propose a model of learning the optimal value of
      decision thresholds based on the theory of semi-Markov decision processes (SMDP).
      In our model, the experimental environment is modeled as an SMDP with each
      "condition" being a "state" and the value of decision thresholds being the
      "actions" taken in those states. The problem of finding the optimal decision
      thresholds then is cast as the stochastic optimal control problem of taking
      actions in each state in the corresponding SMDP such that the average reward rate
      is maximized. Our model utilizes a biologically plausible learning algorithm to
      solve this problem. The simulation results show that at the beginning of learning
      the model choses high values of decision threshold which lead to sub-optimal
      performance. With experience, however, the model learns to lower the value of
      decision thresholds till finally it finds the optimal values. 

PMID- 24904253
TI  - Pharmacological or genetic orexin1 receptor inhibition attenuates MK-801 induced
      glutamate release in mouse cortex.
AB  - The orexin/hypocretin neuropeptides are produced by a cluster of neurons within
      the lateral posterior hypothalamus and participate in neuronal regulation by
      activating their receptors (OX1 and OX2 receptors). The orexin system projects
      widely through the brain and functions as an interface between multiple
      regulatory systems including wakefulness, energy balance, stress, reward, and
      emotion. Recent studies have demonstrated that orexins and glutamate interact at
      the synaptic level and that orexins facilitate glutamate actions. We tested the
      hypothesis that orexins modulate glutamate signaling via OX1 receptors by
      monitoring levels of glutamate in frontal cortex of freely moving mice using
      enzyme coated biosensors under inhibited OX1 receptor conditions. MK-801, an NMDA
      receptor antagonist, was administered subcutaneously (0.178 mg/kg) to indirectly
      disinhibit pyramidal neurons and therefore increase cortical glutamate release.
      In wild-type mice, pretreatment with the OX1 receptor antagonist GSK-1059865 (10
      mg/kg S.C.) which had no effect by itself, significantly attenuated the cortical
      glutamate release elicited by MK-801. OX1 receptor knockout mice had a blunted
      glutamate release response to MK-801 and exhibited about half of the glutamate
      release observed in wild-type mice in agreement with the data obtained with
      transient blockade of OX1 receptors. These results indicate that pharmacological
      (transient) or genetic (permanent) inhibition of the OX1 receptor similarly
      interfere with glutamatergic function in the cortex. Selectively targeting the
      OX1 receptor with an antagonist may normalize hyperglutamatergic states and thus
      may represent a novel therapeutic strategy for the treatment of various
      psychiatric disorders associated with hyperactive states. 

PMID- 24904254
TI  - The feedback-related negativity reflects "more or less" prediction error in
      appetitive and aversive conditions.
AB  - Humans make predictions and use feedback to update their subsequent predictions.
      The feedback-related negativity (FRN) has been found to be sensitive to negative
      feedback as well as negative prediction error, such that the FRN is larger for
      outcomes that are worse than expected. The present study examined prediction
      errors in both appetitive and aversive conditions. We found that the FRN was more
      negative for reward omission vs. wins and for loss omission vs. losses,
      suggesting that the FRN might classify outcomes in a "more-or-less than expected"
      fashion rather than in the "better-or-worse than expected" dimension. Our
      findings challenge the previous notion that the FRN only encodes negative
      feedback and "worse than expected" negative prediction error. 

PMID- 24904257
TI  - A confidence metric for using neurobiological feedback in actor-critic
      reinforcement learning based brain-machine interfaces.
AB  - Brain-Machine Interfaces (BMIs) can be used to restore function in people living
      with paralysis. Current BMIs require extensive calibration that increase the set
      up times and external inputs for decoder training that may be difficult to
      produce in paralyzed individuals. Both these factors have presented challenges in
      transitioning the technology from research environments to activities of daily
      living (ADL). For BMIs to be seamlessly used in ADL, these issues should be
      handled with minimal external input thus reducing the need for a
      technician/caregiver to calibrate the system. Reinforcement Learning (RL) based
      BMIs are a good tool to be used when there is no external training signal and can
      provide an adaptive modality to train BMI decoders. However, RL based BMIs are
      sensitive to the feedback provided to adapt the BMI. In actor-critic BMIs, this
      feedback is provided by the critic and the overall system performance is limited
      by the critic accuracy. In this work, we developed an adaptive BMI that could
      handle inaccuracies in the critic feedback in an effort to produce more accurate
      RL based BMIs. We developed a confidence measure, which indicated how appropriate
      the feedback is for updating the decoding parameters of the actor. The results
      show that with the new update formulation, the critic accuracy is no longer a
      limiting factor for the overall performance. We tested and validated the system
      onthree different data sets: synthetic data generated by an Izhikevich neural
      spiking model, synthetic data with a Gaussian noise distribution, and data
      collected from a non-human primate engaged in a reaching task. All results
      indicated that the system with the critic confidence built in always outperformed
      the system without the critic confidence. Results of this study suggest the
      potential application of the technique in developing an autonomous BMI that does
      not need an external signal for training or extensive calibration. 

PMID- 24904255
TI  - Directed midbrain and spinal cord neurogenesis from pluripotent stem cells to
      model development and disease in a dish.
AB  - Induction of specific neuronal fates is restricted in time and space in the
      developing CNS through integration of extrinsic morphogen signals and intrinsic
      determinants. Morphogens impose regional characteristics on neural progenitors
      and establish distinct progenitor domains. Such domains are defined by unique
      expression patterns of fate determining transcription factors. These processes of
      neuronal fate specification can be recapitulated in vitro using pluripotent stem
      cells. In this review, we focus on the generation of dopamine neurons and motor
      neurons, which are induced at ventral positions of the neural tube through Sonic
      hedgehog (Shh) signaling, and defined at anteroposterior positions by fibroblast
      growth factor (Fgf) 8, Wnt1, and retinoic acid (RA). In vitro utilization of
      these morphogenic signals typically results in the generation of multiple
      neuronal cell types, which are defined at the intersection of these signals. If
      the purpose of in vitro neurogenesis is to generate one cell type only, further
      lineage restriction can be accomplished by forced expression of specific
      transcription factors in a permissive environment. Alternatively, cell-sorting
      strategies allow for selection of neuronal progenitors or mature neurons.
      However, modeling development, disease and prospective therapies in a dish could
      benefit from structured heterogeneity, where desired neurons are appropriately
      synaptically connected and thus better reflect the three-dimensional structure of
      that region. By modulating the extrinsic environment to direct sequential
      generation of neural progenitors within a domain, followed by self-organization
      and synaptic establishment, a reductionist model of that brain region could be
      created. Here we review recent advances in neuronal fate induction in vitro, with
      a focus on the interplay between cell intrinsic and extrinsic factors, and
      discuss the implications for studying development and disease in a dish. 

PMID- 24904258
TI  - Perception and coding of high-frequency spectral notches: potential implications
      for sound localization.
AB  - The interaction of sound waves with the human pinna introduces high-frequency
      notches (5-10 kHz) in the stimulus spectrum that are thought to be useful for
      vertical sound localization. A common view is that these notches are encoded as
      rate profiles in the auditory nerve (AN). Here, we review previously published
      psychoacoustical evidence in humans and computer-model simulations of inner hair
      cell responses to noises with and without high-frequency spectral notches that
      dispute this view. We also present new recordings from guinea pig AN and "ideal
      observer" analyses of these recordings that suggest that discrimination between
      noises with and without high-frequency spectral notches is probably based on the
      information carried in the temporal pattern of AN discharges. The exact nature of
      the neural code involved remains nevertheless uncertain: computer model
      simulations suggest that high-frequency spectral notches are encoded in spike
      timing patterns that may be operant in the 4-7 kHz frequency regime, while "ideal
      observer" analysis of experimental neural responses suggest that an effective cue
      for high-frequency spectral discrimination may be based on sampling rates of
      spike arrivals of AN fibers using non-overlapping time binwidths of between 4 and
      9 ms. Neural responses show that sensitivity to high-frequency notches is
      greatest for fibers with low and medium spontaneous rates than for fibers with
      high spontaneous rates. Based on this evidence, we conjecture that inter-subject
      variability at high-frequency spectral notch detection and, consequently, at
      vertical sound localization may partly reflect individual differences in the
      available number of functional medium- and low-spontaneous-rate fibers. 

PMID- 24904256
TI  - Insult-induced adaptive plasticity of the auditory system.
AB  - The brain displays a remarkable capacity for both widespread and region-specific
      modifications in response to environmental challenges, with adaptive processes
      bringing about the reweighing of connections in neural networks putatively
      required for optimizing performance and behavior. As an avenue for investigation,
      studies centered around changes in the mammalian auditory system, extending from
      the brainstem to the cortex, have revealed a plethora of mechanisms that operate
      in the context of sensory disruption after insult, be it lesion-, noise trauma,
      drug-, or age-related. Of particular interest in recent work are those aspects of
      auditory processing which, after sensory disruption, change at multiple-if not
      all-levels of the auditory hierarchy. These include changes in excitatory,
      inhibitory and neuromodulatory networks, consistent with theories of homeostatic
      plasticity; functional alterations in gene expression and in protein levels; as
      well as broader network processing effects with cognitive and behavioral
      implications. Nevertheless, there abounds substantial debate regarding which of
      these processes may only be sequelae of the original insult, and which may, in
      fact, be maladaptively compelling further degradation of the organism's
      competence to cope with its disrupted sensory context. In this review, we aim to
      examine how the mammalian auditory system responds in the wake of particular
      insults, and to disambiguate how the changes that develop might underlie a
      correlated class of phantom disorders, including tinnitus and hyperacusis, which
      putatively are brought about through maladaptive neuroplastic disruptions to
      auditory networks governing the spatial and temporal processing of acoustic
      sensory information. 

PMID- 24904260
TI  - Online tracking of the contents of conscious perception using real-time fMRI.
AB  - Perception is an active process that interprets and structures the stimulus input
      based on assumptions about its possible causes. We use real-time functional
      magnetic resonance imaging (rtfMRI) to investigate a particularly powerful
      demonstration of dynamic object integration in which the same physical stimulus
      intermittently elicits categorically different conscious object percepts. In this
      study, we simulated an outline object that is moving behind a narrow slit. With
      such displays, the physically identical stimulus can elicit categorically
      different percepts that either correspond closely to the physical stimulus
      (vertically moving line segments) or represent a hypothesis about the underlying
      cause of the physical stimulus (a horizontally moving object that is partly
      occluded). In the latter case, the brain must construct an object from the input
      sequence. Combining rtfMRI with machine learning techniques we show that it is
      possible to determine online the momentary state of a subject's conscious percept
      from time resolved BOLD-activity. In addition, we found that feedback about the
      currently decoded percept increased the decoding rates compared to prior fMRI
      recordings of the same stimulus without feedback presentation. The analysis of
      the trained classifier revealed a brain network that discriminates contents of
      conscious perception with antagonistic interactions between early sensory areas
      that represent physical stimulus properties and higher-tier brain areas. During
      integrated object percepts, brain activity decreases in early sensory areas and
      increases in higher-tier areas. We conclude that it is possible to use BOLD
      responses to reliably track the contents of conscious visual perception with a
      relatively high temporal resolution. We suggest that our approach can also be
      used to investigate the neural basis of auditory object formation and discuss the
      results in the context of predictive coding theory. 

PMID- 24904261
TI  - What we can and cannot (yet) do with functional near infrared spectroscopy.
AB  - Functional near infrared spectroscopy (NIRS) is a relatively new technique
      complimentary to EEG for the development of brain-computer interfaces (BCIs).
      NIRS-based systems for detecting various cognitive and affective states such as
      mental and emotional stress have already been demonstrated in a range of adaptive
      human-computer interaction (HCI) applications. However, before NIRS-BCIs can be
      used reliably in realistic HCI settings, substantial challenges oncerning signal
      processing and modeling must be addressed. Although many of those challenges have
      been identified previously, the solutions to overcome them remain scant. In this
      paper, we first review what can be currently done with NIRS, specifically, NIRS
      based approaches to measuring cognitive and affective user states as well as
      demonstrations of passive NIRS-BCIs. We then discuss some of the primary
      challenges these systems would face if deployed in more realistic settings,
      including detection latencies and motion artifacts. Lastly, we investigate the
      effects of some of these challenges on signal reliability via a quantitative
      comparison of three NIRS models. The hope is that this paper will actively engage
      researchers to acilitate the advancement of NIRS as a more robust and useful tool
      to the BCI community. 

PMID- 24904259
TI  - Advances in non-dopaminergic treatments for Parkinson's disease.
AB  - Since the 1960's treatments for Parkinson's disease (PD) have traditionally been
      directed to restore or replace dopamine, with L-Dopa being the gold standard.
      However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting
      its effectiveness. This has resulted in extensive efforts to develop new
      therapies that work in ways other than restoring or replacing dopamine. Here we
      describe newly emerging non-dopaminergic therapeutic strategies for PD, including
      drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as
      well as GLP-1 agonists, calcium channel blockers, iron chelators, anti
      inflammatories, neurotrophic factors, and gene therapies. We provide a detailed
      account of their success in animal models and their translation to human clinical
      trials. We then consider how advances in understanding the mechanisms of PD,
      genetics, the possibility that PD may consist of multiple disease states,
      understanding of the etiology of PD in non-dopaminergic regions as well as
      advances in clinical trial design will be essential for ongoing advances. We
      conclude that despite the challenges ahead, patients have much cause for optimism
      that novel therapeutics that offer better disease management and/or which slow
      disease progression are inevitable. 

PMID- 24904263
TI  - The functional significance of newly born neurons integrated into olfactory bulb
      circuits.
AB  - The olfactory bulb (OB) is the first central processing center for olfactory
      information connecting with higher areas in the brain, and this neuronal
      circuitry mediates a variety of odor-evoked behavioral responses. In the adult
      mammalian brain, continuous neurogenesis occurs in two restricted regions, the
      subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate
      gyrus. New neurons born in the SVZ migrate through the rostral migratory stream
      and are integrated into the neuronal circuits of the OB throughout life. The
      significance of this continuous supply of new neurons in the OB has been
      implicated in plasticity and memory regulation. Two decades of huge investigation
      in adult neurogenesis revealed the biological importance of integration of new
      neurons into the olfactory circuits. In this review, we highlight the recent
      findings about the physiological functions of newly generated neurons in rodent
      OB circuits and then discuss the contribution of neurogenesis in the brain
      function. Finally, we introduce cutting edge technologies to monitor and
      manipulate the activity of new neurons. 

PMID- 24904264
TI  - Beyond cell replacement: unresolved roles of NG2-expressing progenitors.
AB  - NG2-expressing parenchymal precursors (NG2+p) serve as primary source of
      myelinating oligodendrocytes in both the developing and adult Central Nervous
      System (CNS). However, their abundance, limited differentiation potential at
      adult stages along with stereotypic reaction to injury independent of the extent
      of myelin loss suggest that NG2+p exert functions additional to myelin
      production. In support of this view, NG2+p express a complex battery of molecules
      known to exert neuromodulatory and neuroprotective functions. Further, they
      establish intimate physical associations with the other CNS cell types, receive
      functional synaptic contacts and possess ion channels apt to constantly sense the
      electrical activity of surrounding neurons. These latter features could endow
      NG2+p with the capability to affect neuronal functions with potential homeostatic
      outcomes. Here we summarize and discuss current evidence favoring the view that
      NG2+p can participate in circuit formation, modulate neuronal activity and
      survival in the healthy and injured CNS, and propose perspectives for studies
      that may complete our understanding of NG2+p roles in physiology and pathology. 

PMID- 24904267
TI  - Do we measure gray matter activation with functional diffusion tensor imaging?

PMID- 24904262
TI  - Engram formation in psychiatric disorders.
AB  - Environmental factors substantially influence beginning and progression of mental
      illness, reinforcing or reducing the consequences of genetic vulnerability. Often
      initiated by early traumatic events, "engrams" or memories are formed that may
      give rise to a slow and subtle progression of psychiatric disorders. The large
      delay between beginning and time of onset (diagnosis) may be explained by
      efficient compensatory mechanisms observed in brain metabolism that use optional
      pathways in highly redundant molecular interactions. To this end, research has to
      deal with mechanisms of learning and long-term memory formation, which involves
      (a) epigenetic changes, (b) altered neuronal activities, and (c) changes in
      neuron-glia communication. On the epigenetic level, apparently DNA-methylations
      are more stable than histone modifications, although both closely interact.
      Neuronal activities basically deliver digital information, which clearly can
      serve as basis for memory formation (LTP). However, research in this respect has
      long time neglected the importance of glia. They are more actively involved in
      the control of neuronal activities than thought before. They can both reinforce
      and inhibit neuronal activities by transducing neuronal information from
      frequency-encoded to amplitude and frequency-modulated calcium wave patterns
      spreading in the glial syncytium by use of gap junctions. In this way, they serve
      integrative functions. In conclusion, we are dealing with two concepts of
      encoding information that mutually control each other and synergize: a digital
      (neuronal) and a wave-like (glial) computing, forming neuron-glia functional
      units with inbuilt feedback loops to maintain balance of excitation and
      inhibition. To better understand mental illness, we have to gain more insight
      into the dynamics of adverse environmental impact on those cellular and molecular
      systems. This report summarizes existing knowledge and draws some outline about
      further research in molecular psychiatry. 

PMID- 24904265
TI  - Multimodal decoding and congruent sensory information enhance reaching
      performance in subjects with cervical spinal cord injury.
AB  - Cervical spinal cord injury (SCI) paralyzes muscles of the hand and arm, making
      it difficult to perform activities of daily living. Restoring the ability to
      reach can dramatically improve quality of life for people with cervical SCI. Any
      reaching system requires a user interface to decode parameters of an intended
      reach, such as trajectory and target. A challenge in developing such decoders is
      that often few physiological signals related to the intended reach remain under
      voluntary control, especially in patients with high cervical injuries.
      Furthermore, the decoding problem changes when the user is controlling the motion
      of their limb, as opposed to an external device. The purpose of this study was to
      investigate the benefits of combining disparate signal sources to control reach
      in people with a range of impairments, and to consider the effect of two feedback
      approaches. Subjects with cervical SCI performed robot-assisted reaching,
      controlling trajectories with either shoulder electromyograms (EMGs) or EMGs
      combined with gaze. We then evaluated how reaching performance was influenced by
      task-related sensory feedback, testing the EMG-only decoder in two conditions.
      The first involved moving the arm with the robot, providing congruent sensory
      feedback through their remaining sense of proprioception. In the second, the
      subjects moved the robot without the arm attached, as in applications that
      control external devices. We found that the multimodal-decoding algorithm worked
      well for all subjects, enabling them to perform straight, accurate reaches. The
      inclusion of gaze information, used to estimate target location, was especially
      important for the most impaired subjects. In the absence of gaze information,
      congruent sensory feedback improved performance. These results highlight the
      importance of proprioceptive feedback, and suggest that multi-modal decoders are
      likely to be most beneficial for highly impaired subjects and in tasks where such
      feedback is unavailable. 

PMID- 24904266
TI  - Lactate transport and receptor actions in cerebral malaria.
AB  - Cerebral malaria (CM), caused by Plasmodium falciparum infection, is a prevalent
      neurological disorder in the tropics. Most of the patients are children,
      typically with intractable seizures and high mortality. Current treatment is
      unsatisfactory. Understanding the pathogenesis of CM is required in order to
      identify therapeutic targets. Here, we argue that cerebral energy metabolic
      defects are probable etiological factors in CM pathogenesis, because malaria
      parasites consume large amounts of glucose metabolized mostly to lactate.
      Monocarboxylate transporters (MCTs) mediate facilitated transfer, which serves to
      equalize lactate concentrations across cell membranes in the direction of the
      concentration gradient. The equalizing action of MCTs is the basis for lactate's
      role as a volume transmitter of metabolic signals in the brain. Lactate binds to
      the lactate receptor GPR81, recently discovered on brain cells and cerebral blood
      vessels, causing inhibition of adenylyl cyclase. High levels of lactate delivered
      by the parasite at the vascular endothelium may damage the blood-brain barrier,
      disrupt lactate homeostasis in the brain, and imply MCTs and the lactate receptor
      as novel therapeutic targets in CM. 

PMID- 24904268
TI  - Localization of MEG human brain responses to retinotopic visual stimuli with
      contrasting source reconstruction approaches.
AB  - Magnetoencephalography (MEG) allows the physiological recording of human brain
      activity at high temporal resolution. However, spatial localization of the source
      of the MEG signal is an ill-posed problem as the signal alone cannot constrain a
      unique solution and additional prior assumptions must be enforced. An adequate
      source reconstruction method for investigating the human visual system should
      place the sources of early visual activity in known locations in the occipital
      cortex. We localized sources of retinotopic MEG signals from the human brain with
      contrasting reconstruction approaches (minimum norm, multiple sparse priors, and
      beamformer) and compared these to the visual retinotopic map obtained with fMRI
      in the same individuals. When reconstructing brain responses to visual stimuli
      that differed by angular position, we found reliable localization to the
      appropriate retinotopic visual field quadrant by a minimum norm approach and by
      beamforming. Retinotopic map eccentricity in accordance with the fMRI map could
      not consistently be localized using an annular stimulus with any reconstruction
      method, but confining eccentricity stimuli to one visual field quadrant resulted
      in significant improvement with the minimum norm. These results inform the
      application of source analysis approaches for future MEG studies of the visual
      system, and indicate some current limits on localization accuracy of MEG signals.

PMID- 24904269
TI  - Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in
      C57BL/6J mice.
AB  - Some anti-inflammatory medications reduce alcohol consumption in rodent models.
      Inhibition of phosphodiesterases (PDE) increases cAMP and reduces inflammatory
      signaling. Rolipram, an inhibitor of PDE4, markedly reduced ethanol intake and
      preference in mice and reduced ethanol seeking and consumption in alcohol
      preferring fawn-hooded rats (Hu et al., 2011; Wen et al., 2012). To determine if
      these effects were specific for PDE4, we compared nine PDE inhibitors with
      different subtype selectivity: propentofylline (nonspecific), vinpocetine (PDE1),
      olprinone, milrinone (PDE3), zaprinast (PDE5), rolipram, mesopram, piclamilast,
      and CDP840 (PDE4). Alcohol intake was measured in C57BL/6J male mice using 24-h
      two-bottle choice and two-bottle choice with limited (3-h) access to alcohol.
      Only the selective PDE4 inhibitors reduced ethanol intake and preference in the
      24-h two-bottle choice test. For rolipram, piclamilast, and CDP840, this effect
      was observed after the first 6 h but not after the next 18 h. Mesopram, however,
      produced a long-lasting reduction of ethanol intake and preference. In the
      limited access test, rolipram, piclamilast, and mesopram reduced ethanol
      consumption and total fluid intake and did not change preference for ethanol,
      whereas CDP840 reduced both consumption and preference without altering total
      fluid intake. Our results provide novel evidence for a selective role of PDE4 in
      regulating ethanol drinking in mice. We suggest that inhibition of PDE4 may be an
      unexplored target for medication development to reduce excessive alcohol
      consumption. 

PMID- 24904271
TI  - Insights into the role of RD3 in guanylate cyclase trafficking, photoreceptor
      degeneration, and Leber congenital amaurosis.
AB  - Retinal degeneration 3 (RD3) is an evolutionarily conserved 23 kDa protein
      expressed in rod and cone photoreceptor cells. Mutations in the gene encoding RD3
      resulting in unstable non-functional C-terminal truncated proteins are
      responsible for early onset photoreceptor degeneration in Leber Congenital
      Amaurosis 12 patients, the rd3 mice, and the rcd2 collies. Recent studies have
      shown that RD3 interacts with guanylate cyclases GC1 and GC2 in retinal cell
      extracts and HEK293 cells co-expressing GC and RD3. This interaction inhibits GC
      catalytic activity and promotes the exit of GC1 and GC2 from the endoplasmic
      reticulum and their trafficking to photoreceptor outer segments. Adeno-associated
      viral vector delivery of the normal RD3 gene to photoreceptors of the rd3 mouse
      restores GC1 and GC2 expression and outer segment localization and leads to the
      long-term recovery of visual function and photoreceptor cell survival. This
      review focuses on the genetic and biochemical studies that have provided insight
      into the role of RD3 in photoreceptor function and survival. 

PMID- 24904270
TI  - Regulation of intraocular pressure by soluble and membrane guanylate cyclases and
      their role in glaucoma.
AB  - Glaucoma is a progressive optic neuropathy characterized by visual field defects
      that ultimately lead to irreversible blindness (Alward, 2000; Anderson et al.,
      2006). By the year 2020, an estimated 80 million people will have glaucoma, 11
      million of which will be bilaterally blind. Primary open-angle glaucoma (POAG) is
      the most common type of glaucoma. Elevated intraocular pressure (IOP) is
      currently the only risk factor amenable to treatment. How IOP is regulated and
      can be modulated remains a topic of active investigation. Available therapies,
      mostly geared toward lowering IOP, offer incomplete protection, and POAG often
      goes undetected until irreparable damage has been done, highlighting the need for
      novel therapeutic approaches, drug targets, and biomarkers (Heijl et al., 2002;
      Quigley, 2011). In this review, the role of soluble (nitric oxide (NO)-activated)
      and membrane-bound, natriuretic peptide (NP)-activated guanylate cyclases that
      generate the secondary signaling molecule cyclic guanosine monophosphate (cGMP)
      in the regulation of IOP and in the pathophysiology of POAG will be discussed. 

PMID- 24904273
TI  - NF-kappaB signaling regulates myelination in the CNS.
AB  - Besides myelination of neuronal axons by oligodendrocytes to facilitate
      propagation of action potentials, oligodendrocytes also support axon survival and
      function. A key transcription factor involved in these processes is nuclear
      factor-kappaB (NF-kappaB), a hetero or homodimer of the Rel family of proteins,
      including p65, c-Rel, RelB, p50, and p52. Under unstimulated, NF-kappaB remains
      inactive in the cytoplasm through interaction with NF-kappaB inhibitors
      (IkappaBs). Upon activation of NF-kappaB the cytoplasmic IkappaBs gets
      degradated, allowing the translocation of NF-kappaB into the nucleus where the
      dimer binds to the kappaB consensus DNA sequence and regulates gene
      transcription. In this review we describe how oligodendrocytes are, directly or
      indirectly via neighboring cells, regulated by NF-kappaB signaling with
      consequences for innate and adaptive immunity and for regulation of cell
      apoptosis and survival. 

PMID- 24904272
TI  - GSK-3beta, a pivotal kinase in Alzheimer disease.
AB  - Alzheimer disease (AD) is the most common form of age-related dementia. The
      etiology of AD is considered to be multifactorial as only a negligible percentage
      of cases have a familial or genetic origin. Glycogen synthase kinase-3 (GSK-3) is
      regarded as a critical molecular link between the two histopathological hallmarks
      of the disease, namely senile plaques and neurofibrillary tangles. In this
      review, we summarize current data regarding the involvement of this kinase in
      several aspects of AD development and progression, as well as key observations
      highlighting GSK-3 as one of the most relevant targets for AD treatment. 

PMID- 24904274
TI  - Cellular function and pathological role of ATP13A2 and related P-type transport
      ATPases in Parkinson's disease and other neurological disorders.
AB  - Mutations in ATP13A2 lead to Kufor-Rakeb syndrome, a parkinsonism with dementia.
      ATP13A2 belongs to the P-type transport ATPases, a large family of primary active
      transporters that exert vital cellular functions. However, the cellular function
      and transported substrate of ATP13A2 remain unknown. To discuss the role of
      ATP13A2 in neurodegeneration, we first provide a short description of the
      architecture and transport mechanism of P-type transport ATPases. Then, we
      briefly highlight key P-type ATPases involved in neuronal disorders such as the
      copper transporters ATP7A (Menkes disease), ATP7B (Wilson disease), the
      Na(+)/K(+)-ATPases ATP1A2 (familial hemiplegic migraine) and ATP1A3 (rapid-onset
      dystonia parkinsonism). Finally, we review the recent literature of ATP13A2 and
      discuss ATP13A2's putative cellular function in the light of what is known
      concerning the functions of other, better-studied P-type ATPases. We critically
      review the available data concerning the role of ATP13A2 in heavy metal transport
      and propose a possible alternative hypothesis that ATP13A2 might be a flippase.
      As a flippase, ATP13A2 may transport an organic molecule, such as a lipid or a
      peptide, from one membrane leaflet to the other. A flippase might control local
      lipid dynamics during vesicle formation and membrane fusion events. 

PMID- 24904275
TI  - LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter
      release through modulation of LRRK2 macro-molecular complex.
AB  - Mutations in Leucine-rich repeat kinase 2 gene (LRRK2) are associated with
      familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that
      consists of multiple domains executing several functions, including GTP
      hydrolysis, kinase activity, and protein binding. Robust evidence suggests that
      LRRK2 acts at the synaptic site as a molecular hub connecting synaptic vesicles
      to cytoskeletal elements via a complex panel of protein-protein interactions.
      Here we investigated the impact of pharmacological inhibition of LRRK2 kinase
      activity on synaptic function. Acute treatment with LRRK2 inhibitors reduced the
      frequency of spontaneous currents, the rate of synaptic vesicle trafficking and
      the release of neurotransmitter from isolated synaptosomes. The investigation of
      complementary models lacking LRRK2 expression allowed us to exclude potential off
      side effects of kinase inhibitors on synaptic functions. Next we studied whether
      kinase inhibition affects LRRK2 heterologous interactions. We found that the
      binding among LRRK2, presynaptic proteins and synaptic vesicles is affected by
      kinase inhibition. Our results suggest that LRRK2 kinase activity influences
      synaptic vesicle release via modulation of LRRK2 macro-molecular complex. 

PMID- 24904280
TI  - Differential regulation of collapsin response mediator protein 2 (CRMP2)
      phosphorylation by GSK3beta and CDK5 following traumatic brain injury.
AB  - Aberrant ion channel function has been heralded as a main underlying mechanism
      driving epilepsy and its symptoms. However, it has become increasingly clear that
      treatment strategies targeting voltage-gated sodium or calcium channels merely
      mask the symptoms of epilepsy without providing disease-modifying benefits. Ion
      channel function is likely only one important cog in a highly complex machine.
      Gross morphological changes, such as reactive sprouting and outgrowth, may also
      play a role in epileptogenesis. Mechanisms responsible for these changes are not
      well-understood. Here we investigate the potential involvement of the neurite
      outgrowth-promoting molecule collapsin response mediator protein 2 (CRMP2). CRMP2
      activity, in this respect, is regulated by phosphorylation state, where
      phosphorylation by a variety of kinases, including glycogen synthase kinase 3
      beta (GSK3beta) renders it inactive. Phosphorylation (inactivation) of CRMP2 was
      decreased at two distinct phases following traumatic brain injury (TBI). While
      reduced CRMP2 phosphorylation during the early phase was attributed to the
      inactivation of GSK3beta, the sustained decrease in CRMP2 phosphorylation in the
      late phase appeared to be independent of GSK3beta activity. Instead, the
      reduction in GSK3beta-phosphorylated CRMP2 was attributed to a loss of priming by
      cyclin-dependent kinase 5 (CDK5), which allows for subsequent phosphorylation by
      GSK3beta. Based on the observation that the proportion of active CRMP2 is
      increased for up to 4 weeks following TBI, it was hypothesized that it may drive
      neurite outgrowth, and therefore, circuit reorganization during this time.
      Therefore, a novel small-molecule tool was used to target CRMP2 in an attempt to
      determine its importance in mossy fiber sprouting following TBI. In this report,
      we demonstrate novel differential regulation of CRMP2 phosphorylation by GSK3beta
      and CDK5 following TBI. 

PMID- 24904276
TI  - Microglia centered pathogenesis in ALS: insights in cell interconnectivity.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common and most aggressive form
      of adult motor neuron (MN) degeneration. The cause of the disease is still
      unknown, but some protein mutations have been linked to the pathological process.
      Loss of upper and lower MNs results in progressive muscle paralysis and
      ultimately death due to respiratory failure. Although initially thought to derive
      from the selective loss of MNs, the pathogenic concept of non-cell-autonomous
      disease has come to the forefront for the contribution of glial cells in ALS, in
      particular microglia. Recent studies suggest that microglia may have a protective
      effect on MN in an early stage. Conversely, activated microglia contribute and
      enhance MN death by secreting neurotoxic factors, and impaired microglial
      function at the end-stage may instead accelerate disease progression. However,
      the nature of microglial-neuronal interactions that lead to MN degeneration
      remains elusive. We review the contribution of the neurodegenerative network in
      ALS pathology, with a special focus on each glial cell type from data obtained in
      the transgenic SOD1G93A rodents, the most widely used model. We further discuss
      the diverse roles of neuroinflammation and microglia phenotypes in the modulation
      of ALS pathology. We provide information on the processes associated with
      dysfunctional cell-cell communication and summarize findings on pathological
      cross-talk between neurons and astroglia, and neurons and microglia, as well as
      on the spread of pathogenic factors. We also highlight the relevance of
      neurovascular disruption and exosome trafficking to ALS pathology. The harmful
      and beneficial influences of NG2 cells, oligodendrocytes and Schwann cells will
      be discussed as well. Insights into the complex intercellular perturbations
      underlying ALS, including target identification, will enhance our efforts to
      develop effective therapeutic approaches for preventing or reversing symptomatic
      progression of this devastating disease. 

PMID- 24904279
TI  - The sodium leak channel, NALCN, in health and disease.
AB  - Ion channels are crucial components of cellular excitability and are involved in
      many neurological diseases. This review focuses on the sodium leak, G protein
      coupled receptors (GPCRs)-activated NALCN channel that is predominantly expressed
      in neurons where it regulates the resting membrane potential and neuronal
      excitability. NALCN is part of a complex that includes not only GPCRs, but also
      UNC-79, UNC-80, NLF-1 and src family of Tyrosine kinases (SFKs). There is growing
      evidence that the NALCN channelosome critically regulates its ion conduction.
      Both in mammals and invertebrates, animal models revealed an involvement in many
      processes such as locomotor behaviors, sensitivity to volatile anesthetics, and
      respiratory rhythms. There is also evidence that alteration in this NALCN
      channelosome can cause a wide variety of diseases. Indeed, mutations in the NALCN
      gene were identified in Infantile Neuroaxonal Dystrophy (INAD) patients, as well
      as in patients with an Autosomal Recessive Syndrome with severe hypotonia, speech
      impairment, and cognitive delay. Deletions in NALCN gene were also reported in
      diseases such as 13q syndrome. In addition, genes encoding NALCN, NLF- 1, UNC-79,
      and UNC-80 proteins may be susceptibility loci for several diseases including
      bipolar disorder, schizophrenia, Alzheimer's disease, autism, epilepsy,
      alcoholism, cardiac diseases and cancer. Although the physiological role of the
      NALCN channelosome is poorly understood, its involvement in human diseases should
      foster interest for drug development in the near future. Toward this goal, we
      review here the current knowledge on the NALCN channelosome in physiology and
      diseases. 

PMID- 24904281
TI  - Selective modulation of cellular voltage-dependent calcium channels by hyperbaric
      pressure-a suggested HPNS partial mechanism.
AB  - Professional deep sea divers experience motor and cognitive impairment, known as
      High Pressure Neurological Syndrome (HPNS), when exposed to pressures of 100 msw
      (1.1 MPa) and above, considered to be the result of synaptic transmission
      alteration. Previous studies have indicated modulation of presynaptic Ca(2+)
      currents at high pressure. We directly measured for the first time pressure
      effects on the currents of voltage dependent Ca(2+) channels (VDCCs) expressed in
      Xenopus oocytes. Pressure selectivity augmented the current in CaV1.2 and
      depressed it in CaV3.2 channels. Pressure application also affected the channels'
      kinetics, such as TRise, TDecay. Pressure modulation of VDCCs seems to play an
      important role in generation of HPNS signs and symptoms. 

PMID- 24904282
TI  - The ventricular-subventricular zone: a source of oligodendrocytes in the adult
      brain.

PMID- 24904277
TI  - Modulation of GABAergic transmission in development and neurodevelopmental
      disorders: investigating physiology and pathology to gain therapeutic
      perspectives.
AB  - During mammalian ontogenesis, the neurotransmitter GABA is a fundamental
      regulator of neuronal networks. In neuronal development, GABAergic signaling
      regulates neural proliferation, migration, differentiation, and neuronal-network
      wiring. In the adult, GABA orchestrates the activity of different neuronal cell
      types largely interconnected, by powerfully modulating synaptic activity. GABA
      exerts these functions by binding to chloride-permeable ionotropic GABAA
      receptors and metabotropic GABAB receptors. According to its functional
      importance during development, GABA is implicated in a number of
      neurodevelopmental disorders such as autism, Fragile X, Rett syndrome, Down
      syndrome, schizophrenia, Tourette's syndrome and neurofibromatosis. The strength
      and polarity of GABAergic transmission is continuously modulated during
      physiological, but also pathological conditions. For GABAergic transmission
      through GABAA receptors, strength regulation is achieved by different mechanisms
      such as modulation of GABAA receptors themselves, variation of intracellular
      chloride concentration, and alteration in GABA metabolism. In the never-ending
      effort to find possible treatments for GABA-related neurological diseases, of
      great importance would be modulating GABAergic transmission in a safe and
      possibly physiological way, without the dangers of either silencing network
      activity or causing epileptic seizures. In this review, we will discuss the
      different ways to modulate GABAergic transmission normally at work both during
      physiological and pathological conditions. Our aim is to highlight new research
      perspectives for therapeutic treatments that reinstate natural and physiological
      brain functions in neuro-pathological conditions. 

PMID- 24904284
TI  - Extended two-photon microscopy in live samples with Bessel beams: steadier focus,
      faster volume scans, and simpler stereoscopic imaging.
AB  - Two-photon microscopy has revolutionized functional cellular imaging in tissue,
      but although the highly confined depth of field (DOF) of standard set-ups yields
      great optical sectioning, it also limits imaging speed in volume samples and ease
      of use. For this reason, we recently presented a simple and retrofittable
      modification to the two-photon laser-scanning microscope which extends the DOF
      through the use of an axicon (conical lens). Here we demonstrate three
      significant benefits of this technique using biological samples commonly employed
      in the field of neuroscience. First, we use a sample of neurons grown in culture
      and move it along the z-axis, showing that a more stable focus is achieved
      without compromise on transverse resolution. Second, we monitor 3D population
      dynamics in an acute slice of live mouse cortex, demonstrating that faster
      volumetric scans can be conducted. Third, we acquire a stereoscopic image of
      neurons and their dendrites in a fixed sample of mouse cortex, using only two
      scans instead of the complete stack and calculations required by standard
      systems. Taken together, these advantages, combined with the ease of integration
      into pre-existing systems, make the extended depth-of-field imaging based on
      Bessel beams a strong asset for the field of microscopy and life sciences in
      general. 

PMID- 24904283
TI  - Strategies to increase the activity of microglia as efficient protectors of the
      brain against infections.
AB  - In healthy individuals, infections of the central nervous system (CNS) are
      comparatively rare. Based on the ability of microglial cells to phagocytose and
      kill pathogens and on clinical findings in immunocompromised patients with CNS
      infections, we hypothesize that an intact microglial function is crucial to
      protect the brain from infections. Phagocytosis of pathogens by microglial cells
      can be stimulated by agonists of receptors of the innate immune system. Enhancing
      this pathway to increase the resistance of the brain to infections entails the
      risk of inducing collateral damage to the nervous tissue. The diversity of
      microglial cells opens avenue to selectively stimulate sub-populations
      responsible for the defence against pathogens without stimulating sub-populations
      which are responsible for collateral damage to the nervous tissue.
      Palmitoylethanolamide (PEA), an endogenous lipid, increased phagocytosis of
      bacteria by microglial cells in vitro without a measurable proinflammatory
      effect. It was tested clinically apparently without severe side effects.
      Glatiramer acetate increased phagocytosis of latex beads by microglia and
      monocytes, and dimethyl fumarate enhanced elimination of human immunodeficiency
      virus from infected macrophages without inducing a release of proinflammatory
      compounds. Therefore, the discovery of compounds which stimulate the elimination
      of pathogens without collateral damage of neuronal structures appears an
      achievable goal. PEA and, with limitations, glatiramer acetate and dimethyl
      fumarate appear promising candidates. 

PMID- 24904285
TI  - siRNA screen of ES cell-derived motor neurons identifies novel regulators of
      tetanus toxin and neurotrophin receptor trafficking.
AB  - Neurons rely on the long-range transport of several signaling molecules such as
      neurotrophins and their receptors, which are required for neuronal development,
      function and survival. However, the nature of the machinery controlling the
      trafficking of signaling endosomes containing activated neurotrophin receptors
      has not yet been completely elucidated. We aimed to identify new players involved
      in the dynamics of neurotrophin signaling endosomes using a medium-throughput
      unbiased siRNA screening approach to quantify the intracellular accumulation of
      two fluorescently tagged reporters: the binding fragment of tetanus neurotoxin
      (HCT), and an antibody directed against the neurotrophin receptor p75(NTR). This
      screen performed in motor neurons differentiated from mouse embryonic stem (ES)
      cells identified a number of candidate genes encoding molecular motors and motor
      adaptor proteins involved in regulating the intracellular trafficking of these
      probes. Bicaudal D homolog 1 (BICD1), a molecular motor adaptor with pleiotropic
      roles in intracellular trafficking, was selected for further analyses, which
      revealed that BICD1 regulates the intracellular trafficking of HCT and
      neurotrophin receptors and likely plays an important role in nervous system
      development and function. 

PMID- 24904287
TI  - Spatially selective photoconductive stimulation of live neurons.
AB  - Synaptic activity is intimately linked to neuronal structure and function.
      Stimulation of live cultured primary neurons, coupled with fluorescent indicator
      imaging, is a powerful technique to assess the impact of synaptic activity on
      neuronal protein trafficking and function. Current technology for neuronal
      stimulation in culture include chemical techniques or microelectrode or
      optogenetic based techniques. While technically powerful, chemical stimulation
      has limited spatial resolution and microelectrode and optogenetic techniques
      require specialized equipment and expertise. We report an optimized and improved
      technique for laser based photoconductive stimulation of live neurons using an
      inverted confocal microscope that overcomes these limitations. The advantages of
      this approach include its non-invasive nature and adaptability to temporal and
      spatial manipulation. We demonstrate that the technique can be manipulated to
      achieve spatially selective stimulation of live neurons. Coupled with live
      imaging of fluorescent indicators, this simple and efficient technique should
      allow for significant advances in neuronal cell biology. 

PMID- 24904286
TI  - Biophysical properties of presynaptic short-term plasticity in hippocampal
      neurons: insights from electrophysiology, imaging and mechanistic models.
AB  - Hippocampal neurons show different types of short-term plasticity (STP). Some
      exhibit facilitation of their synaptic responses and others depression. In this
      review we discuss presynaptic biophysical properties behind heterogeneity in STP
      in hippocampal neurons such as alterations in vesicle priming and docking,
      fusion, neurotransmitter filling and vesicle replenishment. We look into what
      types of information electrophysiology, imaging and mechanistic models have given
      about the time scales and relative impact of the different properties on STP with
      an emphasis on the use of mechanistic models as complementary tools to
      experimental procedures. Taken together this tells us that it is possible for a
      multitude of different mechanisms to underlie the same STP pattern, even though
      some are more important in specific cases, and that mechanistic models can be
      used to integrate the biophysical properties to see which mechanisms are more
      important in specific cases of STP. 

PMID- 24904288
TI  - Involvement of ClC-3 chloride/proton exchangers in controlling glutamatergic
      synaptic strength in cultured hippocampal neurons.
AB  - ClC-3 is a member of the CLC family of anion channels and transporters that
      localizes to early and late endosomes as well as to synaptic vesicles (SV). Its
      genetic disruption in mouse models results in pronounced hippocampal and retinal
      neurodegeneration, suggesting that ClC-3 might be important for normal excitatory
      and/or inhibitory neurotransmission in central neurons. To characterize the role
      of ClC-3 in glutamate accumulation in SV we compared glutamatergic synaptic
      transmission in cultured hippocampal neurons from WT and Clcn3-/- mice. In Clcn3
      /- neurons the amplitude and frequency of miniature as well as the amplitudes of
      action-potential evoked EPSCs were significantly increased as compared to WT
      neurons. The low-affinity competitive AMPA receptor antagonist gamma-DGG reduced
      the quantal size of synaptic events more effectively in WT than in Clcn3-/-
      neurons, whereas no difference was observed for the high-affinity competitive non
      NMDA antagonist NBQX. Paired pulse ratios of evoked EPSCs were significantly
      reduced, whereas the size of the readily releasable pool was not affected by the
      genetic ablation of ClC-3. Electron microscopy revealed increased volumes of SV
      in hippocampi of Clcn3-/- mice. Our findings demonstrate that ClC-3 controls fast
      excitatory synaptic transmission by regulating the amount of neurotransmitter as
      well as the release probability of SV. These results provide novel insights into
      the role of ClC-3 in synaptic transmission and identify excessive glutamate
      release as a likely basis of neurodegeneration in Clcn3-/-. 

PMID- 24904290
TI  - TLR4-mediated brain inflammation halts neurogenesis: impact of hormonal
      replacement therapy.
AB  - Experimental and epidemiological data show that the severity and the duration of
      brain inflammation are attenuated in females compared to males. This attenuated
      brain inflammation is ascribed to 17beta-estradiol. However, several studies
      suggest that 17beta-estradiol is also endowed with proinflammatory properties.
      The aim of the present study is to assess the effect of hormonal replacement
      therapies on lipopolysaccharide (LPS)-induced brain inflammation and its
      consequent effect on newly born neurons. Bilaterally ovariectomized rats received
      intrastriatal injection of LPS (250 ng/MUl) and were subsequently given daily
      subcutaneous injections of either vehicle, 17beta-estradiol (25 MUg/kg) or 17beta
      estradiol and progesterone (5 mg/kg). Microglial activation and newly born
      neurons in the rostral migratory stream were monitored using double
      immunofluorescence. Nuclear factor kappaB (NFkappaB) signaling pathway and its
      target inflammatory proteins were assessed by either western blot [cyclooxygenase
      2 (COX-2) and interleukin-6 (IL-6)] or enzyme-linked immunosorbent assay [tumor
      necrosis factor-alpha (TNF-alpha)]. LPS-induced activation of microglia, promoted
      NFkappaB signaling pathway and enhanced the production of proinflammatory
      proteins (TNF-alpha and COX-2). These proinflammatory responses were not
      attenuated by 17beta-estradiol injection. Supplementation of 17beta-estradiol
      with progesterone significantly dampened these proinflammatory processes.
      Interestingly, LPS-induced brain inflammation dampened the number of newly born
      neurons in the rostral migratory stream. Administration of combined 17beta
      estradiol and progesterone resulted in a significantly higher number of newly
      born neurons when compared to those seen in rats given either vehicle or 17beta
      estradiol alone. These data strongly suggest that combined 17beta-estradiol and
      progesterone, and not 17beta-estradiol alone, rescues neurogenesis from the
      deleterious effect of brain inflammation likely via the inhibition of the
      signaling pathways leading to the activation of proinflammatory genes. 

PMID- 24904289
TI  - CXCL12 modulation of CXCR4 and CXCR7 activity in human glioblastoma stem-like
      cells and regulation of the tumor microenvironment.
AB  - Chemokines are crucial autocrine and paracrine players in tumor development. In
      particular, CXCL12, through its receptors CXCR4 and CXCR7, affects tumor
      progression by controlling cancer cell survival, proliferation and migration,
      and, indirectly, via angiogenesis or recruiting immune cells. Glioblastoma (GBM)
      is the most prevalent primary malignant brain tumor in adults and despite current
      multimodal therapies it remains almost incurable. The aggressive and recurrent
      phenotype of GBM is ascribed to high growth rate, invasiveness to normal brain,
      marked angiogenesis, ability to escape the immune system and resistance to
      standard of care therapies. Tumor molecular and cellular heterogeneity severely
      hinders GBM therapeutic improvement. In particular, a subpopulation of chemo- and
      radio-therapy resistant tumorigenic cancer stem-like cells (CSCs) is believed to
      be the main responsible for tumor cell dissemination to the brain. GBM cells
      display heterogeneous expression levels of CXCR4 and CXCR7 that are overexpressed
      in CSCs, representing a molecular correlate for the invasive potential of GBM.
      The microenvironment contribution in GBM development is increasingly emphasized.
      An interplay exists between CSCs, differentiated GBM cells, and the
      microenvironment, mainly through secreted chemokines (e.g., CXCL12) causing
      recruitment of fibroblasts, endothelial, mesenchymal and inflammatory cells to
      the tumor, via specific receptors such as CXCR4. This review covers recent
      developments on the role of CXCL12/CXCR4-CXCR7 networks in GBM progression and
      the potential translational impact of their targeting. The biological and
      molecular understanding of the heterogeneous GBM cell behavior, phenotype and
      signaling is still limited. Progress in the identification of chemokine-dependent
      mechanisms that affect GBM cell survival, trafficking and chemo-attractive
      functions, opens new perspectives for development of more specific therapeutic
      approaches that include chemokine-based drugs. 

PMID- 24904291
TI  - Deregulated expression of cytoskeleton related genes in the spinal cord and
      sciatic nerve of presymptomatic SOD1(G93A) Amyotrophic Lateral Sclerosis mouse
      model.
AB  - Early molecular events related to cytoskeleton are poorly described in
      Amyotrophic Lateral Sclerosis (ALS), especially in the Schwann cell (SC), which
      offers strong trophic support to motor neurons. Database for Annotation,
      Visualization and Integrated Discovery (DAVID) tool identified cytoskeleton
      related genes by employing the Cellular Component Ontology (CCO) in a large gene
      profiling of lumbar spinal cord and sciatic nerve of presymptomatic SOD1(G93A)
      mice. One and five CCO terms related to cytoskeleton were described from the
      spinal cord deregulated genes of 40 days (actin cytoskeleton) and 80 days
      (microtubule cytoskeleton, cytoskeleton part, actin cytoskeleton, neurofilament
      cytoskeleton, and cytoskeleton) old transgene mice, respectively. Also, four
      terms were depicted from the deregulated genes of sciatic nerve of 60 days old
      transgenes (actin cytoskeleton, cytoskeleton part, microtubule cytoskeleton and
      cytoskeleton). Kif1b was the unique deregulated gene in more than one studied
      region or presymptomatic age. The expression of Kif1b [quantitative polymerase
      chain reaction (qPCR)] elevated in the lumbar spinal cord (40 days old) and
      decreased in the sciatic nerve (60 days old) of presymptomatic ALS mice, results
      that were in line to microarray findings. Upregulation (24.8 fold) of Kif1b was
      seen in laser microdissected enriched immunolabeled motor neurons from the spinal
      cord of 40 days old presymptomatic SOD1(G93A) mice. Furthermore, Kif1b was
      dowregulated in the sciatic nerve Schwann cells of presymptomatic ALS mice (60
      days old) that were enriched by means of cell microdissection (6.35 fold), cell
      sorting (3.53 fold), and primary culture (2.70 fold) technologies. The gene
      regulation of cytoskeleton molecules is an important occurrence in motor neurons
      and Schwann cells in presymptomatic stages of ALS and may be relevant in the
      dying back mechanisms of neuronal death. Furthermore, a differential regulation
      of Kif1b in the spinal cord and sciatic nerve cells emerged as key event in ALS. 

PMID- 24904293
TI  - Distinctive behavioral and cellular responses to fluoxetine in the mouse model
      for Fragile X syndrome.
AB  - Fluoxetine is used as a therapeutic agent for autism spectrum disorder (ASD),
      including Fragile X syndrome (FXS). The treatment often associates with
      disruptive behaviors such as agitation and disinhibited behaviors in FXS. To
      identify mechanisms that increase the risk to poor treatment outcome, we
      investigated the behavioral and cellular effects of fluoxetine on adult Fmr1
      knockout (KO) mice, a mouse model for FXS. We found that fluoxetine reduced
      anxiety-like behavior of both wild-type and Fmr1 KO mice seen as shortened
      latency to enter the center area in the open field test. In Fmr1 KO mice,
      fluoxetine normalized locomotor hyperactivity but abnormally increased
      exploratory activity. Reduced brain-derived neurotrophic factor (BDNF) and
      increased TrkB receptor expression levels in the hippocampus of Fmr1 KO mice
      associated with inappropriate coping responses under stressful condition and
      abolished antidepressant activity of fluoxetine. Fluoxetine response in the cell
      proliferation was also missing in the hippocampus of Fmr1 KO mice when compared
      with wild-type controls. The postnatal mRNA expression of serotonin transporter
      (SERT) was reduced in the thalamic nuclei of Fmr1 KO mice during the time of
      transient innervation of somatosensory neurons suggesting that developmental
      changes of SERT expression were involved in the differential cellular and
      behavioral responses to fluoxetine in wild-type and Fmr1 mice. The results
      indicate that changes of BDNF/TrkB signaling contribute to differential
      behavioral responses to fluoxetine among individuals with ASD. 

PMID- 24904294
TI  - Engineering a thalamo-cortico-thalamic circuit on SpiNNaker: a preliminary study
      toward modeling sleep and wakefulness.
AB  - We present a preliminary study of a thalamo-cortico-thalamic (TCT) implementation
      on SpiNNaker (Spiking Neural Network architecture), a brain inspired hardware
      platform designed to incorporate the inherent biological properties of
      parallelism, fault tolerance and energy efficiency. These attributes make
      SpiNNaker an ideal platform for simulating biologically plausible computational
      models. Our focus in this work is to design a TCT framework that can be simulated
      on SpiNNaker to mimic dynamical behavior similar to Electroencephalogram (EEG)
      time and power-spectra signatures in sleep-wake transition. The scale of the
      model is minimized for simplicity in this proof-of-concept study; thus the total
      number of spiking neurons is ~1000 and represents a "mini-column" of the
      thalamocortical tissue. All data on model structure, synaptic layout and
      parameters is inspired from previous studies and abstracted at a level that is
      appropriate to the aims of the current study as well as computationally suitable
      for model simulation on a small 4-chip SpiNNaker system. The initial results from
      selective deletion of synaptic connectivity parameters in the model show
      similarity with EEG power spectra characteristics of sleep and wakefulness. These
      observations provide a positive perspective and a basis for future implementation
      of a very large scale biologically plausible model of thalamo-cortico-thalamic
      interactivity-the essential brain circuit that regulates the biological sleep
      wake cycle and associated EEG rhythms. 

PMID- 24904296
TI  - Unsupervised classification of neocortical activity patterns in neonatal and pre
      juvenile rodents.
AB  - Flexible communication within the brain, which relies on oscillatory activity, is
      not confined to adult neuronal networks. Experimental evidence has documented the
      presence of discontinuous patterns of oscillatory activity already during early
      development. Their highly variable spatial and time-frequency organization has
      been related to region specificity. However, it might be equally due to the
      absence of unitary criteria for classifying the early activity patterns, since
      they have been mainly characterized by visual inspection. Therefore, robust and
      unbiased methods for categorizing these discontinuous oscillations are needed for
      increasingly complex data sets from different labs. Here, we introduce an
      unsupervised detection and classification algorithm for the discontinuous
      activity patterns of rodents during early development. For this, in a first step
      time windows with discontinuous oscillations vs. epochs of network "silence" were
      identified. In a second step, the major features of detected events were
      identified and processed by principal component analysis for deciding on their
      contribution to the classification of different oscillatory patterns. Finally,
      these patterns were categorized using an unsupervised cluster algorithm. The
      results were validated on manually characterized neonatal spindle bursts (SB),
      which ubiquitously entrain neocortical areas of rats and mice, and prelimbic
      nested gamma spindle bursts (NG). Moreover, the algorithm led to satisfactory
      results for oscillatory events that, due to increased similarity of their
      features, were more difficult to classify, e.g., during the pre-juvenile
      developmental period. Based on a linear classification, the optimal number of
      features to consider increased with the difficulty of detection. This algorithm
      allows the comparison of neonatal and pre-juvenile oscillatory patterns in their
      spatial and temporal organization. It might represent a first step for the
      unbiased elucidation of activity patterns during development. 

PMID- 24904297
TI  - Interplay between low threshold voltage-gated K(+) channels and synaptic
      inhibition in neurons of the chicken nucleus laminaris along its frequency axis.
AB  - Central auditory neurons that localize sound in horizontal space have specialized
      intrinsic and synaptic cellular mechanisms to tightly control the threshold and
      timing for action potential generation. However, the critical interplay between
      intrinsic voltage-gated conductances and extrinsic synaptic conductances in
      determining neuronal output are not well understood. In chicken, neurons in the
      nucleus laminaris (NL) encode sound location using interaural time difference
      (ITD) as a cue. Along the tonotopic axis of NL, there exist robust differences
      among low, middle, and high frequency (LF, MF, and HF, respectively) neurons in a
      variety of neuronal properties such as low threshold voltage-gated K(+) (LTK)
      channels and depolarizing inhibition. This establishes NL as an ideal model to
      examine the interactions between LTK currents and synaptic inhibition across the
      tonotopic axis. Using whole-cell patch clamp recordings prepared from chicken
      embryos (E17-E18), we found that LTK currents were larger in MF and HF neurons
      than in LF neurons. Kinetic analysis revealed that LTK currents in MF neurons
      activated at lower voltages than in LF and HF neurons, whereas the inactivation
      of the currents was similar across the tonotopic axis. Surprisingly, blockade of
      LTK currents using dendrotoxin-I (DTX) tended to broaden the duration and
      increase the amplitude of the depolarizing inhibitory postsynaptic potentials
      (IPSPs) in NL neurons without dependence on coding frequency regions. Analyses of
      the effects of DTX on inhibitory postsynaptic currents led us to interpret this
      unexpected observation as a result of primarily postsynaptic effects of LTK
      currents on MF and HF neurons, and combined presynaptic and postsynaptic effects
      in LF neurons. Furthermore, DTX transferred subthreshold IPSPs to spikes. Taken
      together, the results suggest a critical role for LTK currents in regulating
      inhibitory synaptic strength in ITD-coding neurons at various frequencies. 

PMID- 24904298
TI  - mRNA expression profile of serotonin receptor subtypes and distribution of
      serotonergic terminations in marmoset brain.
AB  - To better understand serotonin function in the primate brain, we examined the
      mRNA expression patterns of all the 13 members of the serotonin receptor (5HTR)
      family, by in situ hybridization (ISH) and the distribution of serotonergic
      terminations by serotonin transporter (SERT) protein immunohistochemical
      analysis. Ten of the 13 5HTRs showed significant mRNA expressions in the marmoset
      brain. Our study shows several new features of the organization of serotonergic
      systems in the marmoset brain. (1) The thalamus expressed only a limited number
      of receptor subtypes compared with the cortex, hippocampus, and other subcortical
      regions. (2) In the cortex, there are layer-selective and area-selective mRNA
      expressions of 5HTRs. (3) Highly localized mRNA expressions of 5HT1F and 5HT3A
      were observed. (4) There was a conspicuous overlap of the mRNA expressions of
      receptor subtypes known to have somatodendritic localization of receptor proteins
      with dense serotonergic terminations in the visual cortex, the central lateral
      (CL) nucleus of the thalamus, the presubiculum, and the medial mammillary nucleus
      of the hypothalamus. This suggests a high correlation between serotonin
      availability and receptor expression at these locations. (5) The 5HTRs show
      differences in mRNA expression pattern between the marmoset and mouse cortices
      whereas the patterns of both the species were much similar in the hippocampus. We
      discuss the possible roles of 5HTRs in the marmoset brain revealed by the
      analysis of their overall mRNA expression patterns. 

PMID- 24904299
TI  - New perspectives on catecholaminergic regulation of executive circuits: evidence
      for independent modulation of prefrontal functions by midbrain dopaminergic and
      noradrenergic neurons.
AB  - Cognitive functions associated with prefrontal cortex (PFC), such as working
      memory and attention, are strongly influenced by catecholamine [dopamine (DA) and
      norepinephrine (NE)] release. Midbrain dopaminergic neurons in the ventral
      tegmental area and noradrenergic neurons in the locus coeruleus are major sources
      of DA and NE to the PFC. It is traditionally believed that DA and NE neurons are
      homogeneous with highly divergent axons innervating multiple terminal fields and
      once released, DA and NE individually or complementarily modulate the prefrontal
      functions and other brain regions. However, recent studies indicate that both DA
      and NE neurons in the mammalian brain are heterogeneous with a great degree of
      diversity, including their developmental lineages, molecular phenotypes,
      projection targets, afferent inputs, synaptic connectivity, physiological
      properties, and behavioral functions. These diverse characteristics could
      potentially endow DA and NE neurons with distinct roles in executive function,
      and alterations in their responses to genetic and epigenetic risk factors during
      development may contribute to distinct phenotypic and functional changes in
      disease states. In this review of recent literature, we discuss how these
      advances in DA and NE neurons change our thinking of catecholamine influences in
      cognitive functions in the brain, especially functions related to PFC. We review
      how the projection-target specific populations of neurons in these two systems
      execute their functions in both normal and abnormal conditions. Additionally, we
      explore what open questions remain and suggest where future research needs to
      move in order to provide a novel insight into the cause of neuropsychiatric
      disorders related to DA and NE systems. 

PMID- 24904300
TI  - Severe drug-induced repetitive behaviors and striatal overexpression of VAChT in
      ChAT-ChR2-EYFP BAC transgenic mice.
AB  - In drug users, drug-related cues alone can induce dopamine release in the dorsal
      striatum. Instructive cues activate inputs to the striatum from both dopaminergic
      and cholinergic neurons, which are thought to work together to support motor
      learning and motivated behaviors. Imbalances in these neuromodulatory influences
      can impair normal action selection and might thus contribute to pathologically
      repetitive and compulsive behaviors such as drug addiction. Dopamine and
      acetylcholine can have either antagonistic or synergistic effects on behavior,
      depending on the state of the animal and the receptor signaling systems at play.
      Semi-synchronized activation of cholinergic interneurons in the dorsal striatum
      drives dopamine release via presynaptic nicotinic acetylcholine receptors located
      on dopamine terminals. Nicotinic receptor blockade is known to diminish abnormal
      repetitive behaviors (stereotypies) induced by psychomotor stimulants. By
      contrast, blockade of postsynaptic acetylcholine muscarinic receptors in the
      dorsomedial striatum exacerbates drug-induced stereotypy, exemplifying how
      different acetylcholine receptors can also have opposing effects. Although
      acetylcholine release is known to be altered in animal models of drug addiction,
      predicting whether these changes will augment or diminish drug-induced behaviors
      thus remains a challenge. Here, we measured amphetamine-induced stereotypy in BAC
      transgenic mice that have been shown to overexpress the vesicular acetylcholine
      transporter (VAChT) with consequent increased acetylcholine release. We found
      that drug-induced stereotypies, consisting of confined sniffing and licking
      behaviors, were greatly increased in the transgenic mice relative to sibling
      controls, as was striatal VAChT protein. These findings suggest that VAChT
      mediated increases in acetylcholine could be critical in exacerbating drug
      induced stereotypic behaviors and promoting exaggerated behavioral fixity. 

PMID- 24904303
TI  - Brainstem projections of neurons located in various subdivisions of the
      dorsolateral hypothalamic area-an anterograde tract-tracing study.
AB  - The projections from the dorsolateral hypothalamic area (DLH) to the lower
      brainstem have been investigated by using biotinylated dextran amine (BDA), an
      anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial
      hypothalamus, perifornical area, lateral hypothalamic area), and further
      subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA
      into individual DLH subdivisions, the correct sites of injections were controlled
      histologically, and the distribution patterns of BDA-positive fibers were mapped
      on serial sections between the hypothalamus and spinal cord in 22 rats. BDA
      labeled fibers were observable over 100 different brainstem areas, nuclei, or
      subdivisions. Injections into the 8 DLH subdivisions established distinct
      topographical patterns. In general, the density of labeled fibers was low in the
      lower brainstem. High density of fibers was seen only 4 of the 116 areas: in the
      lateral and ventrolateral parts of the periaqueductal gray, the Barrington's, and
      the pedunculopontine tegmental nuclei. All of the biogenic amine cell groups in
      the lower brainstem (9 noradrenaline, 3 adrenaline, and 9 serotonin cell groups)
      received labeled fibers, some of them from all, or at least 7 DLH subdivisions,
      mainly from perifornical and ventral lateral hypothalamic neurons. Some of the
      tegmental nuclei and nuclei of the reticular formation were widely innervated,
      although the density of the BDA-labeled fibers was generally low. No definitive
      descending BDA-positive pathway, but long-run solitaire BDA-labeled fibers were
      seen in the lower brainstem. These descending fibers joined some of the large
      tracts or fasciculi in the brainstem. The distribution pattern of BDA-positive
      fibers of DLH origin throughout the lower brainstem was comparable to patterns of
      previously published orexin- or melanin-concentrating hormone-immunoreactive
      fibers with somewhat differences. 

PMID- 24904301
TI  - Historical first descriptions of Cajal-Retzius cells: from pioneer studies to
      current knowledge.
AB  - Santiago Ramon y Cajal developed a great body of scientific research during the
      last decade of 19th century, mainly between 1888 and 1892, when he published more
      than 30 manuscripts. The neuronal theory, the structure of dendrites and spines,
      and fine microscopic descriptions of numerous neural circuits are among these
      studies. In addition, numerous cell types (neuronal and glial) were described by
      Ramon y Cajal during this time using this "reazione nera" or Golgi method. Among
      these neurons were the special cells of the molecular layer of the neocortex.
      These cells were also termed Cajal cells or Retzius cells by other colleagues.
      Today these cells are known as Cajal-Retzius cells. From the earliest
      description, several biological aspects of these fascinating cells have been
      analyzed (e.g., cell morphology, physiological properties, origin and cellular
      fate, putative function during cortical development, etc). In this review we will
      summarize in a temporal basis the emerging knowledge concerning this cell
      population with specific attention the pioneer studies of Santiago Ramon y Cajal.

PMID- 24904302
TI  - The Cajal school and the physiological role of astrocytes: a way of thinking.
AB  - Cajal is widely recognized by the scientific community for his important
      contributions to our knowledge of the neuronal organization of the nervous
      system. His studies on neuroglial cells are less recognized, yet they are no less
      relevant to our current understanding of the cellular bases of brain structure.
      Two pioneering studies published a century ago -"Something about the
      physiological significance of neuroglia" (Ramon y Cajal, 1897) and "A
      contribution to the understanding of neuroglia in the human brain" (Ramon y
      Cajal, 1913)-focused on glial cells and their role in brain physiology. Novel
      findings obtained using state-of-the-art and sophisticated technologies largely
      confirm many of the groundbreaking hypotheses proposed by Cajal related to the
      structural-functional properties of neuroglia. Here we propose to the reader a
      journey guided by the ideas of Cajal through the recent findings on the
      functional significance of astrocytes, the most abundant neuroglial cell type in
      the nervous system. Astrocyte-neuron interaction, which represents an emerging
      field in current neuroscience with important implications for our understanding
      of the cellular processes underlying brain function, has its roots in many of the
      original concepts proposed by Cajal. 

PMID- 24904304
TI  - Revisiting a historic human brain with magnetic resonance imaging - the first
      description of a divided central sulcus.
AB  - In 1860 and 1862, the German physiologist Wagner published two studies, in which
      he compared the cortical surfaces of brain specimens. This provided the first
      account of a rare anatomical variation - bridges across the central sulci in both
      hemispheres connecting the forward and backward facing central convolutions in
      one of the brains. The serendipitous rediscovery of the preserved historic brain
      specimen in the collections at Gottingen University, being mistaken as the brain
      of the mathematician C.F. Gauss, allowed us to further investigate the morphology
      of the bridges Wagner had described with magnetic resonance imaging (MRI). On the
      historic lithograph, current photographs and MRI surface reconstructions of the
      brain, a connection across the central sulcus can only be seen in the left
      hemisphere. In the right hemisphere, contrary to the description of Wagner, a
      connecting structure is only present across the post-central sulcus. MRI reveals
      that the left-hemispheric bridge extends into the depth of the sulcus, forming a
      transverse connection between the two opposing gyri. This rare anatomical
      variation, generally not associated with neurological symptoms, would nowadays be
      categorized as a divided central sulcus. The left-hemispheric connection seen
      across the post-central sulcus, represents the very common case of a segmented
      post-central sulcus. MRI further disclosed a connection across the right
      hemispheric central sulcus, which terminates just below the surface of the brain
      and is therefore not depicted on the historical lithography. This explains the
      apparent inconsistency between the bilateral description of bridges across the
      central sulci and the unilateral appearance on the brain surface. The results are
      discussed based on the detailed knowledge of anatomists of the late 19th century,
      who already recognized the divided central sulcus as an extreme variation of a
      deep convolution within the central sulcus. 

PMID- 24904305
TI  - Three counting methods agree on cell and neuron number in chimpanzee primary
      visual cortex.
AB  - Determining the cellular composition of specific brain regions is crucial to our
      understanding of the function of neurobiological systems. It is therefore useful
      to identify the extent to which different methods agree when estimating the same
      properties of brain circuitry. In this study, we estimated the number of neuronal
      and non-neuronal cells in the primary visual cortex (area 17 or V1) of both
      hemispheres from a single chimpanzee. Specifically, we processed samples
      distributed across V1 of the right hemisphere after cortex was flattened into a
      sheet using two variations of the isotropic fractionator cell and neuron counting
      method. We processed the left hemisphere as serial brain slices for stereological
      investigation. The goal of this study was to evaluate the agreement between these
      methods in the most direct manner possible by comparing estimates of cell density
      across one brain region of interest in a single individual. In our hands, these
      methods produced similar estimates of the total cellular population
      (approximately 1 billion) as well as the number of neurons (approximately 675
      million) in chimpanzee V1, providing evidence that both techniques estimate the
      same parameters of interest. In addition, our results indicate the strengths of
      each distinct tissue preparation procedure, highlighting the importance of
      attention to anatomical detail. In summary, we found that the isotropic
      fractionator and the stereological optical fractionator produced concordant
      estimates of the cellular composition of V1, and that this result supports the
      conclusion that chimpanzees conform to the primate pattern of exceptionally high
      packing density in V1. Ultimately, our data suggest that investigators can
      optimize their experimental approach by using any of these counting methods to
      obtain reliable cell and neuron counts. 

PMID- 24904306
TI  - Active learning of neuron morphology for accurate automated tracing of neurites.
AB  - Automating the process of neurite tracing from light microscopy stacks of images
      is essential for large-scale or high-throughput quantitative studies of neural
      circuits. While the general layout of labeled neurites can be captured by many
      automated tracing algorithms, it is often not possible to differentiate reliably
      between the processes belonging to different cells. The reason is that some
      neurites in the stack may appear broken due to imperfect labeling, while others
      may appear fused due to the limited resolution of optical microscopy. Trained
      neuroanatomists routinely resolve such topological ambiguities during manual
      tracing tasks by combining information about distances between branches, branch
      orientations, intensities, calibers, tortuosities, colors, as well as the
      presence of spines or boutons. Likewise, to evaluate different topological
      scenarios automatically, we developed a machine learning approach that combines
      many of the above mentioned features. A specifically designed confidence measure
      was used to actively train the algorithm during user-assisted tracing procedure.
      Active learning significantly reduces the training time and makes it possible to
      obtain less than 1% generalization error rates by providing few training
      examples. To evaluate the overall performance of the algorithm a number of image
      stacks were reconstructed automatically, as well as manually by several trained
      users, making it possible to compare the automated traces to the baseline inter
      user variability. Several geometrical and topological features of the traces were
      selected for the comparisons. These features include the total trace length, the
      total numbers of branch and terminal points, the affinity of corresponding
      traces, and the distances between corresponding branch and terminal points. Our
      results show that when the density of labeled neurites is sufficiently low,
      automated traces are not significantly different from manual reconstructions
      obtained by trained users. 

PMID- 24904307
TI  - Selective alterations of neurons and circuits related to early memory loss in
      Alzheimer's disease.
AB  - A progressive loss of episodic memory is a well-known clinical symptom that
      characterizes Alzheimer's disease (AD). The beginning of this loss of memory has
      been associated with the very early, pathological accumulation of tau and
      neuronal degeneration observed in the entorhinal cortex (EC). Tau-related
      pathology is thought to then spread progressively to the hippocampal formation
      and other brain areas as the disease progresses. The major cortical afferent
      source of the hippocampus and dentate gyrus is the EC through the perforant
      pathway. At least two main circuits participate in the connection between EC and
      the hippocampus; one originating in layer II and the other in layer III of the EC
      giving rise to the classical trisynaptic (ECII -> dentate gyrus -> CA3 -> CA1)
      and monosynaptic (ECIII -> CA1) circuits. Thus, the study of the early
      pathological changes in these circuits is of great interest. In this review, we
      will discuss mainly the alterations of the granule cell neurons of the dentate
      gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to
      the possible differential alterations of these two main circuits. 

PMID- 24904308
TI  - Adult neurogenesis and its anatomical context in the hippocampus of three mole
      rat species.
AB  - African mole-rats (family Bathyergidae) are small to medium sized, long-lived,
      and strictly subterranean rodents that became valuable animal models as a result
      of their longevity and diversity in social organization. The formation and
      integration of new hippocampal neurons in adult mammals (adult hippocampal
      neurogenesis, AHN) correlates negatively with age and positively with habitat
      complexity. Here we present quantitative data on AHN in wild-derived mole-rats of
      1 year and older, and briefly describe its anatomical context including markers
      of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats
      (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus
      pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed.
      Compared to other rodents, the hippocampal formation in mole-rats is small, but
      shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of
      the calcium-binding proteins differ from those seen in rodents; e.g., calbindin
      in CA3 of naked mole-rats distributes similar to the pattern seen in early
      primate development, and calbindin staining extends into the stratum lacunosum
      moleculare of Cape mole-rats. Proliferating cells and young neurons are found in
      low numbers in the hippocampus of all three mole-rat species. Resident granule
      cell numbers are low as well. Proliferating cells expressed as a percentage of
      resident granule cells are in the range of other rodents, while the percentage of
      young neurons is lower than that observed in surface dwelling rodents. Between
      mole-rat species, we observed no difference in the percentage of proliferating
      cells. The percentages of young neurons are high in social highveld and naked
      mole-rats, and low in solitary Cape mole-rats. The findings support that
      proliferation is regulated independently of average life expectancy and habitat.
      Instead, neuronal differentiation reflects species-specific demands, which appear
      lower in subterranean rodents. 

PMID- 24904309
TI  - Mechanism of parkinsonian neuronal oscillations in the primate basal ganglia:
      some considerations based on our recent work.
AB  - Accumulating evidence suggests that abnormal neuronal oscillations in the basal
      ganglia (BG) contribute to the manifestation of parkinsonian symptoms. In this
      article, we would like to summarize our recent work on the mechanism underlying
      abnormal oscillations in the parkinsonian state and discuss its significance in
      pathophysiology of Parkinson's disease. We recorded neuronal activity in the BG
      of parkinsonian monkeys treated with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine. Systemic administration of L-DOPA alleviated parkinsonian
      motor signs and decreased abnormal neuronal oscillations (8-15 Hz) in the
      internal (GPi) and external (GPe) segments of the globus pallidus and the
      subthalamic nucleus (STN). Inactivation of the STN by muscimol (GABAA receptor
      agonist) injection also ameliorated parkinsonian signs and suppressed GPi
      oscillations. The blockade of glutamatergic inputs to the STN by local
      microinjection of a mixture of 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic
      acid (glutamatergic NMDA receptor antagonist) and 1,2,3,4-tetrahydro-6-nitro-2,3
      dioxo-benzo[f]quinoxaline-7-sulfonamide (glutamatergic AMPA/kainate receptor
      antagonist) suppressed neuronal oscillations in the STN. STN oscillations were
      also attenuated by the blockade of GABAergic neurotransmission from the GPe to
      the STN by muscimol inactivation of the GPe. These results suggest that cortical
      glutamatergic inputs to the STN and reciprocal GPe-STN interconnections are both
      important for the generation and amplification of the oscillatory activity of GPe
      and STN neurons in the parkinsonian state. The oscillatory activity in the STN is
      subsequently transmitted to the GPi and may contribute to manifestation of
      parkinsonian symptoms. 

PMID- 24904310
TI  - Diffusion tensor imaging in children with unilateral hearing loss: a pilot study.
AB  - OBJECTIVE: Language acquisition was assumed to proceed normally in children with
      unilateral hearing loss (UHL) since they have one functioning ear. However,
      children with UHL score poorly on speech-language tests and have higher rates of
      educational problems compared to normal hearing (NH) peers. Diffusion tensor
      imaging (DTI) is an imaging modality used to measure microstructural integrity of
      brain white matter. The purpose of this pilot study was to investigate
      differences in fractional anisotropy (FA) and mean diffusivity (MD) in hearing-
      and non-hearing-related structures in the brain between children with UHL and
      their NH siblings. STUDY DESIGN: Prospective observational cohort. SETTING:
      Academic medical center. SUBJECTS AND METHODS: Sixty one children were recruited,
      tested and imaged. Twenty nine children with severe-to-profound UHL were compared
      to 20 siblings with NH using IQ and oral language testing, and MRI with DTI.
      Twelve children had inadequate MRI data. Parents provided demographic data and
      indicated whether children had a need for an individualized educational program
      (IEP) or speech therapy (ST). DTI parameters were measured in auditory and non
      auditory regions of interest (ROIs). Between-group comparisons were evaluated
      with non-parametric tests. RESULTS: Lower FA of left lateral lemniscus was
      observed for children with UHL compared to their NH siblings, as well as trends
      toward differences in other auditory and non-auditory regions. Correlation
      analyses showed associations between several DTI parameters and outcomes in
      children with UHL. Regression analyses revealed relationships between educational
      outcome variables and several DTI parameters, which may provide clinically useful
      information for guidance of speech therapy. DISCUSSION/CONCLUSION: Our data
      suggests that white matter microstructural patterns in several brain regions are
      preserved despite unilateral rather than bilateral auditory input which contrasts
      with findings in patients with bilateral hearing loss.

PMID- 24904311
TI  - Alternation of up and down states at a dynamical phase-transition of a neural
      network with spatiotemporal attractors.
AB  - Complex collective activity emerges spontaneously in cortical circuits in vivo
      and in vitro, such as alternation of up and down states, precise spatiotemporal
      patterns replay, and power law scaling of neural avalanches. We focus on such
      critical features observed in cortical slices. We study spontaneous dynamics
      emerging in noisy recurrent networks of spiking neurons with sparse structured
      connectivity. The emerging spontaneous dynamics is studied, in presence of noise,
      with fixed connections. Note that no short-term synaptic depression is used. Two
      different regimes of spontaneous activity emerge changing the connection strength
      or noise intensity: a low activity regime, characterized by a nearly exponential
      distribution of firing rates with a maximum at rate zero, and a high activity
      regime, characterized by a nearly Gaussian distribution peaked at a high rate for
      high activity, with long-lasting replay of stored patterns. Between this two
      regimes, a transition region is observed, where firing rates show a bimodal
      distribution, with alternation of up and down states. In this region, one
      observes neuronal avalanches exhibiting power laws in size and duration, and a
      waiting time distribution between successive avalanches which shows a non
      monotonic behavior. During periods of high activity (up states) consecutive
      avalanches are correlated, since they are part of a short transient replay
      initiated by noise focusing, and waiting times show a power law distribution. One
      can think at this critical dynamics as a reservoire of dynamical patterns for
      memory functions. 

PMID- 24904312
TI  - Effects of ketamine and propofol on motor evoked potentials elicited by
      intracranial microstimulation during deep brain stimulation.
AB  - Few preclinical or clinical studies have evaluated the effect of anesthetics on
      motor evoked potentials (MEPs), either alone or in the presence of conditioning
      stimuli such as deep brain stimulation (DBS). In this study we evaluated the
      effects of two commonly used anesthetic agents, propofol and ketamine (KET), on
      MEPs elicited by intra-cortical microstimulation of the motor cortex in a rodent
      model with and without DBS of the dentatothalamocortical (DTC) pathway. The
      effects of propofol anesthesia on MEP amplitudes during DTC DBS were found to be
      highly dose dependent. Standard, but not high, dose propofol potentiated the
      facilitatory effects of 30 Hz DTC DBS on MEPs. This facilitation was sustained
      and phase-dependent indicating that, compared to high dose propofol, standard
      dose propofol has a beta-band excitatory effect on cortical networks. In
      contrast, KET anesthetic demonstrated a monotonic relationship with increasing
      frequencies of stimulation, such that the highest frequency of stimulation
      resulted in the greatest MEP amplitude. KET also showed phase dependency but less
      pronounced than standard dose propofol. The results underscore the importance of
      better understanding the complex effects of anesthetics on cortical networks and
      exogenous stimuli. Choice of anesthetic agents and dosing may significantly
      confound or even skew research outcomes, including experimentation in novel DBS
      indications and paradigms. 

PMID- 24904313
TI  - Pharmacological enhancement of memory or cognition in normal subjects.
AB  - The possibility of expanding memory or cognitive capabilities above the levels in
      high functioning individuals is a topic of intense discussion among scientists
      and in society at large. The majority of animal studies use behavioral endpoint
      measures; this has produced valuable information but limited predictability for
      human outcomes. Accordingly, several groups are pursuing a complementary strategy
      with treatments targeting synaptic events associated with memory encoding or
      forebrain network operations. Transcription and translation figure prominently in
      substrate work directed at enhancement. Notably, the question of why new proteins
      would be needed for a now-forming memory given that learning-driven synthesis
      presumably occurred throughout the immediate past has been largely ignored.
      Despite this conceptual problem, and some controversy, recent studies have
      reinvigorated the idea that selective gene manipulation is a plausible route to
      enhancement. Efforts to improve memory by facilitating synaptic encoding of
      information have also progressed, in part due of breakthroughs on mechanisms that
      stabilize learning-related, long-term potentiation (LTP). These advances point to
      a reductionistic hypothesis for a diversity of experimental results on
      enhancement, and identify under-explored possibilities. Cognitive enhancement
      remains an elusive goal, in part due to the difficulty of defining the target.
      The popular view of cognition as a collection of definable computations seems to
      miss the fluid, integrative process experienced by high functioning individuals.
      The neurobiological approach obviates these psychological issues to directly test
      the consequences of improving throughput in networks underlying higher order
      behaviors. The few relevant studies testing drugs that selectively promote
      excitatory transmission indicate that it is possible to expand cortical networks
      engaged by complex tasks and that this is accompanied by capabilities not found
      in normal animals. 

PMID- 24904315
TI  - Interhemispheric claustral circuits coordinate sensory and motor cortical areas
      that regulate exploratory behaviors.
AB  - The claustrum has a role in the interhemispheric transfer of certain types of
      sensorimotor information. Whereas the whisker region in rat motor (M1) cortex
      sends dense projections to the contralateral claustrum, the M1 forelimb
      representation does not. The claustrum sends strong ipsilateral projections to
      the whisker regions in M1 and somatosensory (S1) cortex, but its projections to
      the forelimb cortical areas are weak. These distinctions suggest that one
      function of the M1 projections to the contralateral claustrum is to coordinate
      the cortical areas that regulate peripheral sensor movements during behaviors
      that depend on bilateral sensory acquisition. If this hypothesis is true, then
      similar interhemispheric circuits should interconnect the frontal eye fields
      (FEF) with the contralateral claustrum and its network of projections to vision
      related cortical areas. To test this hypothesis, anterograde and retrograde
      tracers were placed in physiologically-defined parts of the FEF and primary
      visual cortex (V1) in rats. We observed dense FEF projections to the
      contralateral claustrum that terminated in the midst of claustral neurons that
      project to both FEF and V1. While the FEF inputs to the claustrum come
      predominantly from the contralateral hemisphere, the claustral projections to FEF
      and V1 are primarily ipsilateral. Detailed comparison of the present results with
      our previous studies on somatomotor claustral circuitry revealed a well-defined
      functional topography in which the ventral claustrum is connected with visuomotor
      cortical areas and the dorsal regions are connected with somatomotor areas. These
      results suggest that subregions within the claustrum play a critical role in
      coordinating the cortical areas that regulate the acquisition of modality
      specific sensory information during exploration and other behaviors that require
      sensory attention. 

PMID- 24904314
TI  - Distinct regions of the cerebellum show gray matter decreases in autism, ADHD,
      and developmental dyslexia.
AB  - Differences in cerebellar structure have been identified in autism spectrum
      disorder (ASD), attention deficit hyperactivity disorder (ADHD), and
      developmental dyslexia. However, it is not clear if different cerebellar regions
      are involved in each disorder, and thus whether cerebellar anatomical differences
      reflect a generic developmental vulnerability or disorder-specific
      characteristics. To clarify this, we conducted an anatomic likelihood estimate
      (ALE) meta-analysis on voxel-based morphometry (VBM) studies which compared ASD
      (17 studies), ADHD (10 studies), and dyslexic (10 studies) participants with age
      matched typically-developing (TD) controls. A second ALE analysis included
      studies in which the cerebellum was a region of interest (ROI). There were no
      regions of significantly increased gray matter (GM) in the cerebellum in ASD,
      ADHD, or dyslexia. Data from ASD studies revealed reduced GM in the inferior
      cerebellar vermis (lobule IX), left lobule VIIIB, and right Crus I. In ADHD,
      significantly decreased GM was found bilaterally in lobule IX, whereas
      participants with developmental dyslexia showed GM decreases in left lobule VI.
      There was no overlap between the cerebellar clusters identified in each disorder.
      We evaluated the functional significance of the regions revealed in both whole
      brain and cerebellar ROI ALE analyses using Buckner and colleagues' 7-network
      functional connectivity map available in the SUIT cerebellar atlas. The
      cerebellar regions identified in ASD showed functional connectivity with
      frontoparietal, default mode, somatomotor, and limbic networks; in ADHD, the
      clusters were part of dorsal and ventral attention networks; and in dyslexia, the
      clusters involved ventral attention, frontoparietal, and default mode networks.
      The results suggest that different cerebellar regions are affected in ASD, ADHD,
      and dyslexia, and these cerebellar regions participate in functional networks
      that are consistent with the characteristic symptoms of each disorder. 

PMID- 24904316
TI  - Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by
      antidromic stimulation.
AB  - In Parkinson's disease (PD), cortical networks show enhanced synchronized
      activity but whether this precedes motor signs is unknown. We investigated this
      question in PINK1(-)/(-) mice, a genetic rodent model of the PARK6 variant of
      familial PD which shows impaired spontaneous locomotion at 16 months. We used two
      photon calcium imaging and whole-cell patch clamp in slices from juvenile (P14
      P21) wild-type or PINK1(-)/(-) mice. We designed a horizontal tilted cortico
      subthalamic slice where the only connection between cortex and subthalamic
      nucleus (STN) is the hyperdirect cortico-subthalamic pathway. We report excessive
      correlation and synchronization in PINK1(-)/(-) M1 cortical networks 15 months
      before motor impairment. The percentage of correlated pairs of neurons and their
      strength of correlation were higher in the PINK1(-)/(-) M1 than in the wild type
      network and the synchronized network events involved a higher percentage of
      neurons. Both features were independent of thalamo-cortical pathways, insensitive
      to chronic levodopa treatment of pups, but totally reversed by antidromic
      invasion of M1 pyramidal neurons by axonal spikes evoked by high frequency
      stimulation (HFS) of the STN. Our study describes an early excess of
      synchronization in the PINK1(-)/(-) cortex and suggests a potential role of
      antidromic activation of cortical interneurons in network desynchronization. Such
      backward effect on interneurons activity may be of importance for HFS-induced
      network desynchronization. 

PMID- 24904318
TI  - Extraction and restoration of hippocampal spatial memories with non-linear
      dynamical modeling.
AB  - To build a cognitive prosthesis that can replace the memory function of the
      hippocampus, it is essential to model the input-output function of the damaged
      hippocampal region, so the prosthetic device can stimulate the downstream
      hippocampal region, e.g., CA1, with the output signal, e.g., CA1 spike trains,
      predicted from the ongoing input signal, e.g., CA3 spike trains, and the
      identified input-output function, e.g., CA3-CA1 model. In order for the
      downstream region to form appropriate long-term memories based on the restored
      output signal, furthermore, the output signal should contain sufficient
      information about the memories that the animal has formed. In this study, we
      verify this premise by applying regression and classification modelings of the
      spatio-temporal patterns of spike trains to the hippocampal CA3 and CA1 data
      recorded from rats performing a memory-dependent delayed non-match-to-sample
      (DNMS) task. The regression model is essentially the multiple-input, multiple
      output (MIMO) non-linear dynamical model of spike train transformation. It
      predicts the output spike trains based on the input spike trains and thus
      restores the output signal. In addition, the classification model interprets the
      signal by relating the spatio-temporal patterns to the memory events. We have
      found that: (1) both hippocampal CA3 and CA1 spike trains contain sufficient
      information for predicting the locations of the sample responses (i.e., left and
      right memories) during the DNMS task; and more importantly (2) the CA1 spike
      trains predicted from the CA3 spike trains by the MIMO model also are sufficient
      for predicting the locations on a single-trial basis. These results show
      quantitatively that, with a moderate number of unitary recordings from the
      hippocampus, the MIMO non-linear dynamical model is able to extract and restore
      spatial memory information for the formation of long-term memories and thus can
      serve as the computational basis of the hippocampal memory prosthesis. 

PMID- 24904317
TI  - Topographical distribution and morphology of NADPH-diaphorase-stained neurons in
      the human claustrum.
AB  - We studied the topographical distribution and morphological characteristics of
      NADPH-diaphorase-positive neurons and fibers in the human claustrum. These
      neurons were seen to be heterogeneously distributed throughout the claustrum.
      Taking into account the size and shape of stained perikarya as well as dendritic
      and axonal characteristics, Nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPHd)-positive neurons were categorized by diameter into three
      types: large, medium and small. Large neurons ranged from 25 to 35 MUm in
      diameter and typically displayed elliptical or multipolar cell bodies. Medium
      neurons ranged from 20 to 25 MUm in diameter and displayed multipolar, bipolar
      and irregular cell bodies. Small neurons ranged from 14 to 20 MUm in diameter and
      most often displayed oval or elliptical cell bodies. Based on dendritic
      characteristics, these neurons were divided into spiny and aspiny subtypes. Our
      findings reveal two populations of NADPHd-positive neurons in the human claustrum
      one comprised of large and medium cells consistent with a projection neuron
      phenotype, the other represented by small cells resembling the interneuron
      phenotype as defined by previous Golgi impregnation studies. 

PMID- 24904319
TI  - Characterization of claustral neurons by comparative gene expression profiling
      and dye-injection analyses.
AB  - The identity of the claustrum as a part of cerebral cortex, and in particular of
      the adjacent insular cortex, has been investigated by connectivity features and
      patterns of gene expression. In the present paper, we mapped the cortical and
      claustral expression of several cortical genes in rodent and macaque monkey
      brains (nurr1, latexin, cux2, and netrinG2) to further assess shared features
      between cortex and claustrum. In mice, these genes were densely expressed in the
      claustrum, but very sparsely in the cortex and not present in the striatum. To
      test whether the cortical vs. claustral cell types can be distinguished by co
      expression of these genes, we performed a panel of double ISH in mouse and
      macaque brain. NetrinG2 and nurr1 genes were co-expressed across entire cortex
      and claustrum, but cux2 and nurr1 were co-expressed only in the insular cortex
      and claustrum. Latexin was expressed, in the macaque, only in the claustrum. The
      nurr1 (+) claustral neurons expressed VGluT1, a marker for cortical glutamatergic
      cells and send cortical projections. Taken together, our data suggest a partial
      commonality between claustral neurons and a subtype of cortical neurons in the
      monkey brain. Moreover, in the embryonic (E110) macaque brain, many nurr1 (+)
      neurons were scattered in the white matter between the claustrum and the insular
      cortex, possibly representing their migratory history. In a second set of
      experiments, we injected Lucifer Yellow intracellularly in mouse and rat slices
      to investigate whether dendrites of insular and claustral neurons can cross the
      border of the two brain regions. Dendrites of claustral neurons did not invade
      the overlying insular territory. In summary, gene expression profile of the
      claustrum is similar to that of the neocortex, in both rodent and macaque brains,
      but with modifications in density of expression and cellular co-localization of
      specific genes. 

PMID- 24904320
TI  - Expression of calcium-binding proteins and selected neuropeptides in the human,
      chimpanzee, and crab-eating macaque claustrum.
AB  - The claustrum is present in all mammalian species examined so far and its
      morphology, chemoarchitecture, physiology, phylogenesis and ontogenesis are still
      a matter of debate. Several morphologically distinct types of immunostained cells
      were described in different mammalian species. To date, a comparative study on
      the neurochemical organization of the human and non-human primates claustrum has
      not been fully described yet, partially due to technical reasons linked to the
      postmortem sampling interval. The present study analyze the localization and
      morphology of neurons expressing parvalbumin (PV), calretinin (CR), NPY, and
      somatostatin (SOM) in the claustrum of man (# 5), chimpanzee (# 1) and crab
      eating monkey (# 3). Immunoreactivity for the used markers was observed in
      neuronal cell bodies and processes distributed throughout the anterior-posterior
      extent of human, chimpanzee and macaque claustrum. Both CR- and PV-immunoreactive
      (ir) neurons were mostly localized in the central and ventral region of the
      claustrum of the three species while SOM- and NPY-ir neurons seemed to be equally
      distributed throughout the ventral-dorsal extent. In the chimpanzee claustrum SOM
      ir elements were not observed. No co-localization of PV with CR was found, thus
      suggesting the existence of two non-overlapping populations of PV and CR-ir
      interneurons. The expression of most proteins (CR, PV, NPY), was similar in all
      species. The only exception was the absence of SOM-ir elements in the claustrum
      of the chimpanzee, likely due to species specific variability. Our data suggest a
      possible common structural organization shared with the adjacent insular region,
      a further element that emphasizes a possible common ontogeny of the claustrum and
      the neocortex. 

PMID- 24904321
TI  - Corticofugal projections induce long-lasting effects on somatosensory responses
      in the trigeminal complex of the rat.
AB  - The sensory information flow at subcortical relay stations is controlled by the
      action of topographic connections from the neocortex. To determinate the
      functional properties of the somatosensory corticofugal projections to the
      principal (Pr5) and caudal spinal (Sp5C) trigeminal nuclei, we performed unitary
      recordings in anesthetized rats. To examine the effect of these cortical
      projections we used tactile stimulation of the whisker and electrical stimulation
      of somatosensory cortices. Corticofugal anatomical projections to Pr5 and Sp5C
      nuclei were detected by using retrograde fluorescent tracers. Neurons projecting
      exclusively to Pr5 were located in the cingulate cortex while neurons projecting
      to both Sp5C and Pr5 nuclei were located in the somatosensory and insular
      cortices (>75% of neurons). Physiological results indicated that primary
      somatosensory cortex produced a short-lasting facilitating or inhibiting effects
      (<5 min) of tactile responses in Pr5 nucleus through activation of NMDA
      glutamatergic or GABAA receptors since effects were blocked by iontophoretically
      application of APV and bicuculline, respectively. In contrast, stimulation of
      secondary somatosensory cortex did not affect most of the Pr5 neurons; however
      both cortices inhibited the nociceptive responses in the Sp5C nucleus through
      activation of glycinergic or GABAA receptors because effects were blocked by
      iontophoretically application of strychnine and bicuculline, respectively. These
      and anatomical results demonstrated that the somatosensory cortices projects to
      Pr5 nucleus to modulate tactile responses by excitatory and inhibitory actions,
      while projections to the Sp5C nucleus control nociceptive sensory transmission by
      only inhibitory effects. Thus, somatosensory cortices may modulate innocuous and
      noxious inputs simultaneously, contributing to the perception of specifically
      tactile or painful sensations. 

PMID- 24904323
TI  - Brain-machine interfaces can accelerate clarification of the principal mysteries
      and real plasticity of the brain.
AB  - This perspective emphasizes that the brain-machine interface (BMI) research has
      the potential to clarify major mysteries of the brain and that such clarification
      of the mysteries by neuroscience is needed to develop BMIs. I enumerate five
      principal mysteries. The first is "how is information encoded in the brain?" This
      is the fundamental question for understanding what our minds are and is related
      to the verification of Hebb's cell assembly theory. The second is "how is
      information distributed in the brain?" This is also a reconsideration of the
      functional localization of the brain. The third is "what is the function of the
      ongoing activity of the brain?" This is the problem of how the brain is active
      during no-task periods and what meaning such spontaneous activity has. The fourth
      is "how does the bodily behavior affect the brain function?" This is the problem
      of brain-body interaction, and obtaining a new "body" by a BMI leads to a
      possibility of changes in the owner's brain. The last is "to what extent can the
      brain induce plasticity?" Most BMIs require changes in the brain's neuronal
      activity to realize higher performance, and the neuronal operant conditioning
      inherent in the BMIs further enhances changes in the activity. 

PMID- 24904324
TI  - Crowdsourcing taste research: genetic and phenotypic predictors of bitter taste
      perception as a model.
AB  - Understanding the influence of taste perception on food choice has captured the
      interest of academics, industry, and the general public, the latter as evidenced
      by the extent of popular media coverage and use of the term supertaster.
      Supertasters are highly sensitive to the bitter tastant propylthiouracil (PROP)
      and its chemical relative phenylthiocarbamide. The well-researched differences in
      taste sensitivity to these bitter chemicals are partially controlled by variation
      in the TAS2R38 gene; however, this variation alone does not explain the
      supertaster phenomenon. It has been suggested that density of papillae, which
      house taste buds, may explain supertasting. To address the unresolved role of
      papillae, we used crowdsourcing in the museum-based Genetics of Taste Lab. This
      community lab is uniquely situated to attract both a large population of human
      subjects and host a team of citizen scientists to research population-based
      questions about human genetics, taste, and health. Using this model, we find that
      PROP bitterness is not in any way predicted by papillae density. This result
      holds within the whole sample, when divided into major diplotypes, and when
      correcting for age, sex, and genotype. Furthermore, it holds when dividing
      participants into oft-used taster status groups. These data argue against the use
      of papillae density in predicting taste sensitivity and caution against imprecise
      use of the term supertaster. Furthermore, it supports a growing volume of
      evidence that sets the stage for hypergeusia, a reconceptualization of heightened
      oral sensitivity that is not based solely on PROP or papillae density. Finally,
      our model demonstrates how community-based research can serve as a unique venue
      for both study participation and citizen science that makes scientific research
      accessible and relevant to people's everyday lives. 

PMID- 24904325
TI  - Phase-amplitude coupling and infraslow (<1 Hz) frequencies in the rat brain:
      relationship to resting state fMRI.
AB  - Resting state functional magnetic resonance imaging (fMRI) can identify network
      alterations that occur in complex psychiatric diseases and behaviors, but its
      interpretation is difficult because the neural basis of the infraslow BOLD
      fluctuations is poorly understood. Previous results link dynamic activity during
      the resting state to both infraslow frequencies in local field potentials (LFP)
      (<1 Hz) and band-limited power in higher frequency LFP (>1 Hz). To investigate
      the relationship between these frequencies, LFPs were recorded from rats under
      two anesthetics: isoflurane and dexmedetomidine. Signal phases were calculated
      from low-frequency LFP and compared to signal amplitudes from high-frequency LFP
      to determine if modulation existed between the two frequency bands (phase
      amplitude coupling). Isoflurane showed significant, consistent phase-amplitude
      coupling at nearly all pairs of frequencies, likely due to the burst-suppression
      pattern of activity that it induces. However, no consistent phase-amplitude
      coupling was observed in rats that were anesthetized with dexmedetomidine. fMRI
      LFP correlations under isoflurane using high frequency LFP were reduced when the
      low frequency LFP's influence was accounted for, but not vice-versa, or in any
      condition under dexmedetomidine. The lack of consistent phase-amplitude coupling
      under dexmedetomidine and lack of shared variance between high frequency and low
      frequency LFP as it relates to fMRI suggests that high and low frequency neural
      electrical signals may contribute differently, possibly even independently, to
      resting state fMRI. This finding suggests that researchers take care in
      interpreting the neural basis of resting state fMRI, as multiple dynamic factors
      in the underlying electrophysiology could be driving any particular observation. 

PMID- 24904322
TI  - Translational studies of goal-directed action as a framework for classifying
      deficits across psychiatric disorders.
AB  - The ability to learn contingencies between actions and outcomes in a dynamic
      environment is critical for flexible, adaptive behavior. Goal-directed actions
      adapt to changes in action-outcome contingencies as well as to changes in the
      reward-value of the outcome. When networks involved in reward processing and
      contingency learning are maladaptive, this fundamental ability can be lost, with
      detrimental consequences for decision-making. Impaired decision-making is a core
      feature in a number of psychiatric disorders, ranging from depression to
      schizophrenia. The argument can be developed, therefore, that seemingly disparate
      symptoms across psychiatric disorders can be explained by dysfunction within
      common decision-making circuitry. From this perspective, gaining a better
      understanding of the neural processes involved in goal-directed action, will
      allow a comparison of deficits observed across traditional diagnostic boundaries
      within a unified theoretical framework. This review describes the key processes
      and neural circuits involved in goal-directed decision-making using evidence from
      animal studies and human neuroimaging. Select studies are discussed to outline
      what we currently know about causal judgments regarding actions and their
      consequences, action-related reward evaluation, and, most importantly, how these
      processes are integrated in goal-directed learning and performance. Finally, we
      look at how adaptive decision-making is impaired across a range of psychiatric
      disorders and how deepening our understanding of this circuitry may offer
      insights into phenotypes and more targeted interventions. 

PMID- 24904326
TI  - Induction of central nervous system plasticity by repetitive transcranial
      magnetic stimulation to promote sensorimotor recovery in incomplete spinal cord
      injury.
AB  - Cortical and spinal cord plasticity may be induced with non-invasive transcranial
      magnetic stimulation to encourage long term potentiation or depression of
      neuronal circuits. Such plasticity inducing stimulation provides an attractive
      approach to promote changes in sensorimotor circuits that have been degraded by
      spinal cord injury (SCI). If residual corticospinal circuits can be conditioned
      appropriately there should be the possibility that the changes are accompanied by
      functional recovery. This article reviews the attempts that have been made to
      restore sensorimotor function and to obtain functional benefits from the
      application of repetitive transcranial magnetic stimulation (rTMS) of the cortex
      following incomplete spinal cord injury. The confounding issues that arise with
      the application of rTMS, specifically in SCI, are enumerated. Finally,
      consideration is given to the potential for rTMS to be used in the restoration of
      bladder and bowel sphincter function and consequent functional recovery of the
      guarding reflex. 

PMID- 24904327
TI  - Spatial cognition, body representation and affective processes: the role of
      vestibular information beyond ocular reflexes and control of posture.
AB  - A growing number of studies in humans demonstrate the involvement of vestibular
      information in tasks that are seemingly remote from well-known functions such as
      space constancy or postural control. In this review article we point out three
      emerging streams of research highlighting the importance of vestibular input: (1)
      Spatial Cognition: Modulation of vestibular signals can induce specific changes
      in spatial cognitive tasks like mental imagery and the processing of numbers.
      This has been shown in studies manipulating body orientation (changing the input
      from the otoliths), body rotation (changing the input from the semicircular
      canals), in clinical findings with vestibular patients, and in studies carried
      out in microgravity. There is also an effect in the reverse direction; top-down
      processes can affect perception of vestibular stimuli. (2) Body Representation:
      Numerous studies demonstrate that vestibular stimulation changes the
      representation of body parts, and sensitivity to tactile input or pain. Thus, the
      vestibular system plays an integral role in multisensory coordination of body
      representation. (3) Affective Processes and Disorders: Studies in psychiatric
      patients and patients with a vestibular disorder report a high comorbidity of
      vestibular dysfunctions and psychiatric symptoms. Recent studies investigated the
      beneficial effect of vestibular stimulation on psychiatric disorders, and how
      vestibular input can change mood and affect. These three emerging streams of
      research in vestibular science are-at least in part-associated with different
      neuronal core mechanisms. Spatial transformations draw on parietal areas, body
      representation is associated with somatosensory areas, and affective processes
      involve insular and cingulate cortices, all of which receive vestibular input.
      Even though a wide range of different vestibular cortical projection areas has
      been ascertained, their functionality still is scarcely understood. 

PMID- 24904329
TI  - A virtual reality task based on animal research - spatial learning and memory in
      patients after the first episode of schizophrenia.
AB  - OBJECTIVES: Cognitive deficit is considered to be a characteristic feature of
      schizophrenia disorder. A similar cognitive dysfunction was demonstrated in
      animal models of schizophrenia. However, the poor comparability of methods used
      to assess cognition in animals and humans could be responsible for low predictive
      validity of current animal models. In order to assess spatial abilities in
      schizophrenia and compare our results with the data obtained in animal models, we
      designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals
      Navigation (vFGN) task. METHODS: Twenty-nine patients after the first psychotic
      episode with schizophrenia symptoms and a matched group of healthy volunteers
      performed the vFGN task. They were required to find and remember four hidden goal
      positions in an enclosed virtual arena. The task consisted of two parts. The
      Reference memory (RM) session with a stable goal position was designed to test
      spatial learning. The Delayed-matching-to-place (DMP) session presented a
      modified working memory protocol designed to test the ability to remember a
      sequence of three hidden goal positions. RESULTS: Data obtained in the RM session
      show impaired spatial learning in schizophrenia patients compared to the healthy
      controls in pointing and navigation accuracy. The DMP session showed impaired
      spatial memory in schizophrenia during the recall of spatial sequence and a
      similar deficit in spatial bias in the probe trials. The pointing accuracy and
      the quadrant preference showed higher sensitivity toward the cognitive deficit
      than the navigation accuracy. Direct navigation to the goal was affected by sex
      and age of the tested subjects. The age affected spatial performance only in
      healthy controls. CONCLUSIONS: Despite some limitations of the study, our results
      correspond well with the previous studies in animal models of schizophrenia and
      support the decline of spatial cognition in schizophrenia, indicating the
      usefulness of the vFGN task in comparative research.

PMID- 24904328
TI  - Getting a grip on problem gambling: what can neuroscience tell us?
AB  - In problem gamblers, diminished cognitive control and increased impulsivity is
      present compared to healthy controls. Moreover, impulsivity has been found to be
      a vulnerability marker for the development of pathological gambling (PG) and
      problem gambling (PrG) and to be a predictor of relapse. In this review, the most
      recent findings on functioning of the brain circuitry relating to impulsivity and
      cognitive control in PG and PrG are discussed. Diminished functioning of several
      prefrontal areas and of the anterior cingulate cortex (ACC) indicate that
      cognitive-control related brain circuitry functions are diminished in PG and PrG
      compared to healthy controls. From the available cue reactivity studies on PG and
      PrG, increased responsiveness towards gambling stimuli in fronto-striatal reward
      circuitry and brain areas related to attentional processing is present compared
      to healthy controls. At this point it is unresolved whether PG is associated with
      hyper- or hypo-activity in the reward circuitry in response to monetary cues.
      More research is needed to elucidate the complex interactions for reward
      responsivity in different stages of gambling and across different types of
      reward. Conflicting findings from basic neuroscience studies are integrated in
      the context of recent neurobiological addiction models. Neuroscience studies on
      the interface between cognitive control and motivational processing are discussed
      in light of current addiction theories. CLINICAL IMPLICATIONS: We suggest that
      innovation in PG therapy should focus on improvement of dysfunctional cognitive
      control and/or motivational functions. The implementation of novel treatment
      methods like neuromodulation, cognitive training and pharmacological
      interventions as add-on therapies to standard treatment in PG and PrG, in
      combination with the study of their effects on brain-behavior mechanisms could
      prove an important clinical step forward towards personalizing and improving
      treatment results in PG.

PMID- 24904330
TI  - Neural correlates of sensorimotor gating: a metabolic positron emission
      tomography study in awake rats.
AB  - Impaired sensorimotor gating occurs in neuropsychiatric disorders such as
      schizophrenia and can be measured using the prepulse inhibition (PPI) paradigm of
      the acoustic startle response. This assay is frequently used to validate animal
      models of neuropsychiatric disorders and to explore the therapeutic potential of
      new drugs. The underlying neural network of PPI has been extensively studied with
      invasive methods and genetic modifications. However, its relevance for healthy
      untreated animals and the functional interplay between startle- and PPI-related
      areas during a PPI session is so far unknown. Therefore, we studied awake rats in
      a PPI paradigm, startle control and background noise control, combined with
      behavioral [(18)F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET).
      Subtractive analyses between conditions were used to identify brain regions
      involved in startle and PPI processing in well-hearing Black hooded rats. For
      correlative analysis with regard to the amount of PPI we also included hearing
      impaired Lister hooded rats that startled more often, because their hearing
      threshold was just below the lowest prepulses. Metabolic imaging showed that the
      brain areas proposed for startle and PPI mediation are active during PPI
      paradigms in healthy untreated rats. More importantly, we show for the first time
      that the whole PPI modulation network is active during "passive" PPI sessions,
      where no selective attention to prepulse or startle stimulus is required. We
      conclude that this reflects ongoing monitoring of stimulus significance and
      constant adjustment of sensorimotor gating. 

PMID- 24904331
TI  - The effects of acute stress exposure on striatal activity during Pavlovian
      conditioning with monetary gains and losses.
AB  - Pavlovian conditioning involves the association of an inherently neutral stimulus
      with an appetitive or aversive outcome, such that the neutral stimulus itself
      acquires reinforcing properties. Across species, this type of learning has been
      shown to involve subcortical brain regions such as the striatum and the amygdala.
      It is less clear, however, how the neural circuitry involved in the acquisition
      of Pavlovian contingencies in humans, particularly in the striatum, is affected
      by acute stress. In the current study, we investigate the effect of acute stress
      exposure on Pavlovian conditioning using monetary reinforcers. Participants
      underwent a partial reinforcement conditioning procedure in which neutral stimuli
      were paired with high and low magnitude monetary gains and losses. A between
      subjects design was used, such that half of the participants were exposed to cold
      stress while the remaining participants were exposed to a no stress control
      procedure. Cortisol measurements and subjective ratings were used as measures of
      stress. We observed an interaction between stress, valence, and magnitude in the
      ventral striatum, with the peak in the putamen. More specifically, the stress
      group exhibited an increased sensitivity to magnitude in the gain domain. This
      effect was driven by those participants who experienced a larger increase in
      circulating cortisol levels in response to the stress manipulation. Taken
      together, these results suggest that acute stress can lead to individual
      differences in circulating cortisol levels which influence the striatum during
      Pavlovian conditioning with monetary reinforcers. 

PMID- 24904332
TI  - The effect of psilocin on memory acquisition, retrieval, and consolidation in the
      rat.
AB  - The involvement of the serotonin system in the pathophysiology of schizophrenia
      has been elucidated by experiments with hallucinogens. Application of a
      hallucinogen to humans leads to changes in perception, cognition, emotions, and
      induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In
      rodent studies, their acute administration affects sensorimotor gating, locomotor
      activity, social behavior, and cognition including working memory, the phenotypes
      are considered as an animal model of schizophrenia. The complexity and
      singularity of human cognition raises questions about the validity of animal
      models utilizing agonists of 5-HT2A receptors. The present study thus
      investigated the effect of psilocin on memory acquisition, reinforced retrieval,
      and memory consolidation in rats. Psilocin is a main metabolite of psilocybin
      acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A
      receptors. First, we tested the effect of psilocin on the acquisition of a
      Carousel maze, a spatial task requiring navigation using distal cues, attention,
      and cognitive coordination. Psilocin significantly impaired the acquisition of
      the Carousel maze at both doses (1 and 4 mg/kg). The higher dose of psilocin
      blocked the learning processes even in an additional session when the rats
      received only saline. Next, we examined the effect of psilocin on reinforced
      retrieval and consolidation in the Morris water maze (MWM). The dose of 4 mg/kg
      disrupted reinforced retrieval in the MWM. However, the application of a lower
      dose was without any significant effect. Finally, neither the low nor high dose
      of psilocin injected post-training caused a deficit in memory consolidation in
      the MWM. Taken together, the psilocin dose dependently impaired the acquisition
      of the Carousel maze and reinforced retrieval in MWM; however, it had no effect
      on memory consolidation. 

PMID- 24904333
TI  - Heterozygous ambra1 deficiency in mice: a genetic trait with autism-like behavior
      restricted to the female gender.
AB  - Autism-spectrum disorders (ASD) are heterogeneous, highly heritable
      neurodevelopmental conditions affecting around 0.5% of the population across
      cultures, with a male/female ratio of approximately 4:1. Phenotypically, ASD are
      characterized by social interaction and communication deficits, restricted
      interests, repetitive behaviors, and reduced cognitive flexibility. Identified
      causes converge at the level of the synapse, ranging from mutation of synaptic
      genes to quantitative alterations in synaptic protein expression, e.g., through
      compromised transcriptional or translational control. We wondered whether reduced
      turnover and degradation of synapses, due to deregulated autophagy, would lead to
      similar phenotypical consequences. Ambra1, strongly expressed in cortex,
      hippocampus, and striatum, is a positive regulator of Beclin1, a principal player
      in autophagosome formation. While homozygosity of the Ambra1 null mutation causes
      embryonic lethality, heterozygous mice with reduced Ambra1 expression are viable,
      reproduce normally, and lack any immediately obvious phenotype. Surprisingly,
      comprehensive behavioral characterization of these mice revealed an autism-like
      phenotype in Ambra1 (+/-) females only, including compromised communication and
      social interactions, a tendency of enhanced stereotypies/repetitive behaviors,
      and impaired cognitive flexibility. Reduced ultrasound communication was found in
      adults as well as pups, which achieved otherwise normal neurodevelopmental
      milestones. These features were all absent in male Ambra1 (+/-) mice. As a first
      hint explaining this gender difference, we found a much stronger reduction of
      Ambra1 protein in the cortex of Ambra1 (+/-) females compared to males. To
      conclude, Ambra1 deficiency can induce an autism-like phenotype. The restriction
      to the female gender of autism-generation by a defined genetic trait is unique
      thus far and warrants further investigation. 

PMID- 24904334
TI  - Orexin receptor antagonist-induced sleep does not impair the ability to wake in
      response to emotionally salient acoustic stimuli in dogs.
AB  - The ability to awaken from sleep in response to important stimuli is a critical
      feature of normal sleep, as is maintaining sleep continuity in the presence of
      irrelevant background noise. Dual orexin receptor antagonists (DORAs) effectively
      promote sleep across species by targeting the evolutionarily conserved wake
      promoting orexin signaling pathway. This study in dogs investigated whether DORA
      induced sleep preserved the ability to awaken appropriately to salient acoustic
      stimuli but remain asleep when exposed to irrelevant stimuli. Sleep and wake in
      response to DORAs, vehicle, GABA-A receptor modulators (diazepam, eszopiclone and
      zolpidem) and antihistamine (diphenhydramine) administration were evaluated in
      telemetry-implanted adult dogs with continuous electrocorticogram, electromyogram
      (EMG), electrooculogram (EOG), and activity recordings. DORAs induced sleep, but
      GABA-A modulators and antihistamine induced paradoxical hyperarousal. Thus,
      salience gating studies were conducted during DORA-22 (0.3, 1, and 5 mg/kg; day
      and night) and vehicle nighttime sleep. The acoustic stimuli were either
      classically conditioned using food reward and positive attention (salient
      stimulus) or presented randomly (neutral stimulus). Once conditioned, the tones
      were presented at sleep times corresponding to maximal DORA-22 exposure. In
      response to the salient stimuli, dogs woke completely from vehicle and orexin
      antagonized sleep across all sleep stages but rarely awoke to neutral stimuli.
      Notably, acute pharmacological antagonism of orexin receptors paired with
      emotionally salient anticipation produced wake, not cataplexy, in a species where
      genetic (chronic) loss of orexin receptor signaling leads to
      narcolepsy/cataplexy. DORA-induced sleep in the dog thereby retains the desired
      capacity to awaken to emotionally salient acoustic stimuli while preserving
      uninterrupted sleep in response to irrelevant stimuli. 

PMID- 24904336
TI  - Sweet lies: neural, visual, and behavioral measures reveal a lack of self-control
      conflict during food choice in weight-concerned women.
AB  - Despite their intentions, weight-concerned individuals generally fail to control
      their eating behavior. However, it is unknown whether this failure is due to a
      lack of effortful self-control, or to not experiencing an internal conflict
      between weight goals and food temptations. The present study used fMRI, eye
      tracking and reaction times to assess the degree of conflict experienced by
      weight-concerned women during food choices that posed either a self-control
      dilemma (i.e., requiring a choice between healthy and palatable foods), or not.
      Contrary to the common assumption in self-control theory that food choices posing
      a self-control dilemma evoke internal conflict, we found that choices requiring
      self-control induced no conflict, as demonstrated by lower reaction times,
      fixation durations, number of gaze switches between snacks, and lower activation
      of the anterior cingulate cortex. Our results suggest that self-control failure
      might be due to a lack of experienced conflict, rather than to failing to act
      upon the perception of such conflict. This implies that effectiveness of weight
      maintenance interventions might be improved if they also focus on increasing the
      ability to detect a self-control dilemma, in addition to the current focus on
      increasing self-regulatory capacity. 

PMID- 24904335
TI  - Behavioral and electrophysiological effects of endocannabinoid and dopaminergic
      systems on salient stimuli.
AB  - Rewarding effects have been related to enhanced dopamine (DA) release in
      corticolimbic and basal ganglia structures. The DAergic and endocannabinoid
      interaction in the responses to reward is described. This study investigated the
      link between endocannabinoid and DAergic transmission in the processes that are
      related to response to two types of reward, palatable food and novelty. Mice
      treated with drugs acting on endocannabinoid system (ECS) (URB597, AM251) or
      DAergic system (haloperidol) were submitted to approach-avoidance conflict tasks
      with palatable food or novelty. In the same mice, the cannabinoid type-1 (CB1)
      mediated GABAergic transmission in medium spiny neurons of the dorsomedial
      striatum was analyzed. The endocannabinoid potentiation by URB597 magnified
      approach behavior for reward (food and novelty) and in parallel inhibited
      dorsostriatal GABAergic neurotransmission. The decreased activity of CB1 receptor
      by AM251 (alone or with URB597) or of DAergic D2 receptor by haloperidol had
      inhibitory effects toward the reward and did not permit the inhibition of
      dorsostriatal GABAergic transmission. When haloperidol was coadministered with
      URB597, a restoration effect on reward and reward-dependent motor activity was
      observed, only if the reward was the palatable food. In parallel, the
      coadministration led to restoring inhibition of CB1-mediated GABAergic
      transmission. Thus, in the presence of simultaneous ECS activation and inhibition
      of DAergic system the response to reward appears to be a stimulus-dependent
      manner. 

PMID- 24904337
TI  - Motor patterns during active electrosensory acquisition.
AB  - Motor patterns displayed during active electrosensory acquisition of information
      seem to be an essential part of a sensory strategy by which weakly electric fish
      actively generate and shape sensory flow. These active sensing strategies are
      expected to adaptively optimize ongoing behavior with respect to either motor
      efficiency or sensory information gained. The tight link between the motor domain
      and sensory perception in active electrolocation make weakly electric fish like
      Gnathonemus petersii an ideal system for studying sensory-motor interactions in
      the form of active sensing strategies. Analyzing the movements and electric
      signals of solitary fish during unrestrained exploration of objects in the dark,
      we here present the first formal quantification of motor patterns used by fish
      during electrolocation. Based on a cluster analysis of the kinematic values we
      categorized the basic units of motion. These were then analyzed for their
      associative grouping to identify and extract short coherent chains of behavior.
      This enabled the description of sensory behavior on different levels of
      complexity: from single movements, over short behaviors to more complex
      behavioral sequences during which the kinematics alter between different
      behaviors. We present detailed data for three classified patterns and provide
      evidence that these can be considered as motor components of active sensing
      strategies. In accordance with the idea of active sensing strategies, we found
      categorical motor patterns to be modified by the sensory context. In addition
      these motor patterns were linked with changes in the temporal sampling in form of
      differing electric organ discharge frequencies and differing spatial
      distributions. The ability to detect such strategies quantitatively will allow
      future research to investigate the impact of such behaviors on sensing. 

PMID- 24904338
TI  - Decreasing ventromedial prefrontal cortex deactivation in risky decision making
      after simulated microgravity: effects of -6 degrees  head-down tilt bed rest.
AB  - Space is characterized by risk and uncertainty. As humans play an important role
      in long-duration space missions, the ability to make risky decisions effectively
      is important for astronauts who spend extended time periods in space. The present
      study used the Balloon Analog Risk Task to conduct both behavioral and fMRI
      experiments to evaluate the effects of simulated microgravity on individuals'
      risk-taking behavior and the neural basis of the effect. The results showed that
      participants' risk-taking behavior was not affected by bed rest. However, we
      found that the ventromedial prefrontal cortex (VMPFC) showed less deactivation
      after bed rest and that the VMPFC activation in the active choice condition
      showed no significant difference between the win outcome and the loss outcome
      after bed rest, although its activation was significantly greater in the win
      outcome than in the loss outcome before bed rest. These results suggested that
      the participants showed a decreased level of value calculation after the bed
      rest. Our findings can contribute to a better understanding of the effect of
      microgravity on individual higher-level cognitive functioning. 

PMID- 24904341
TI  - Comparative chemosensory cognition.

PMID- 24904339
TI  - Local control of striatal dopamine release.
AB  - The mesolimbic and nigrostriatal dopamine (DA) systems play a key role in the
      physiology of reward seeking, motivation and motor control. Importantly, they are
      also involved in the pathophysiology of Parkinson's and Huntington's disease,
      schizophrenia and addiction. Control of DA release in the striatum is tightly
      linked to firing of DA neurons in the ventral tegmental area (VTA) and the
      substantia nigra (SN). However, local influences in the striatum affect release
      by exerting their action directly on axon terminals. For example, endogenous
      glutamatergic and cholinergic activity is sufficient to trigger striatal DA
      release independently of cell body firing. Recent developments involving genetic
      manipulation, pharmacological selectivity or selective stimulation have allowed
      for better characterization of these phenomena. Such termino-terminal forms of
      control of DA release transform considerably our understanding of the mesolimbic
      and nigrostriatal systems, and have strong implications as potential mechanisms
      to modify impaired control of DA release in the diseased brain. Here, we review
      these and related mechanisms and their implications in the physiology of
      ascending DA systems. 

PMID- 24904342
TI  - Oxytocin facilitates social approach behavior in women.
AB  - In challenging environments including both numerous threats and scarce resources,
      the survival of an organism depends on its ability to quickly escape from dangers
      and to seize opportunities to gain rewards. The phylogenetically ancient
      neurohormonal oxytocin (OXT) system has been shown to influence both approach and
      avoidance (AA) behavior in men, but evidence for comparable effects in women is
      still lacking. We thus conducted a series of pharmacological behavioral
      experiments in a randomized double-blind study involving 76 healthy heterosexual
      women treated with either OXT (24 IU) or placebo intranasally. In Experiment 1,
      we tested how OXT influenced the social distance subjects maintained between
      themselves and either a female or male experimenter. In Experiment 2, we applied
      a reaction time based AA task. In Experiment 3 we investigated effects on peri
      personal space by measuring the lateral attentional bias in a line bisection
      task. We found that OXT specifically decreased the distance maintained between
      subjects and the male but not the female experimenter and also accelerated
      approach toward pleasant social stimuli in the AA task. However, OXT did not
      influence the size of peri-personal space, suggesting that it does not alter
      perception of personal space per se, but rather that a social element is
      necessary for OXT's effects on AA behavior to become evident. Taken together, our
      results point to an evolutionarily adaptive mechanism by which OXT in women
      selectively promotes approach behavior in positive social contexts. 

PMID- 24904340
TI  - A neurobiological hypothesis of treatment-resistant depression - mechanisms for
      selective serotonin reuptake inhibitor non-efficacy.
AB  - First-line treatment of major depression includes administration of a selective
      serotonin reuptake inhibitor (SSRI), yet studies suggest that remission rates
      following two trials of an SSRI are <50%. The authors examine the putative
      biological substrates underlying "treatment resistant depression (TRD)" with the
      goal of elucidating novel rationales to treat TRD. We look at relevant articles
      from the preclinical and clinical literature combined with clinical exposure to
      TRD patients. A major focus was to outline pathophysiological mechanisms whereby
      the serotonin system becomes impervious to the desired enhancement of serotonin
      neurotransmission by SSRIs. A complementary focus was to dissect neurotransmitter
      systems, which serve to inhibit the dorsal raphe. We propose, based on a body of
      translational studies, TRD may not represent a simple serotonin deficit state but
      rather an excess of midbrain peri-raphe serotonin and subsequent deficit at key
      fronto-limbic projection sites, with ultimate compromise in serotonin-mediated
      neuroplasticity. Glutamate, serotonin, noradrenaline, and histamine are activated
      by stress and exert an inhibitory effect on serotonin outflow, in part by
      "flooding" 5-HT1A autoreceptors by serotonin itself. Certain factors putatively
      exacerbate this scenario - presence of the short arm of the serotonin transporter
      gene, early-life adversity and comorbid bipolar disorder - each of which has been
      associated with SSRI-treatment resistance. By utilizing an incremental approach,
      we provide a system for treating the TRD patient based on a strategy of rescuing
      serotonin neurotransmission from a state of SSRI-induced dorsal raphe stasis.
      This calls for "stacked" interventions, with an SSRI base, targeting, if
      necessary, the glutamatergic, serotonergic, noradrenergic, and histaminergic
      systems, thereby successively eliminating the inhibitory effects each are capable
      of exerting on serotonin neurons. Future studies are recommended to test this
      biologically based approach for treatment of TRD. 

PMID- 24904343
TI  - The behavioral and immunological impact of maternal separation: a matter of
      timing.
AB  - Maternal separation (MS), an early life stressful event, has been demonstrated to
      trigger neuropsychiatric disorders later in life, in particular depression.
      Experiments using rodents subjected to MS protocols have been very informative
      for the establishment of this association. However, the mechanism by which MS
      leads to neuropsychiatric disorders is far from being understood. This is
      probably associated with the multifactorial nature of depression but also with
      the fact that different research MS protocols have been used (that vary on
      temporal windows and time of exposure to MS). In the present study, MS was
      induced in rats in two developmental periods: for 6 h per day for 14 days between
      postnatal days 2-15 (MS2-15) and 7-20 (MS7-20). These two periods were defined to
      differ essentially on the almost complete (MS2-15) or partial (MS7-20) overlap
      with the stress hypo-responsive period. Behavioral, immunological, and endocrine
      parameters, frequently associated with depressive-like behavior, were analyzed in
      adulthood. Irrespectively from the temporal window, both MS exposure periods led
      to increased sera corticosterone levels. However, only MS2-15 animals displayed
      depressive and anxious-like behaviors. Moreover, MS2-15 was also the only group
      presenting alterations in the immune system, displaying decreased percentage of
      CD8(+) T cells, increased spleen T cell CD4/CD8 ratio, and thymocytes with
      increased resistance to dexamethasone-induced cell death. A linear regression
      model performed to predict depressive-like behavior showed that both
      corticosterone levels and T cell CD4/CD8 ratio explained 37% of the variance
      observed in depressive-like behavior. Overall, these findings highlight the
      existence of "critical periods" for early life stressful events to exert
      programing effects on both central and peripheral systems, which are of relevance
      for distinct patterns of susceptibility to emotional disorders later in life. 

PMID- 24904344
TI  - Getting ready for an emotion: specific premotor brain activities for self
      administered emotional pictures.
AB  - Emotional perception has been extensively studied, but only a few studies have
      investigated the brain activity preceding exposure to emotional stimuli,
      especially when they are triggered by the subject himself. Here, we sought to
      investigate the emotional expectancy by means of movement related cortical
      potentials (MRCPs) in a self-paced task, in which the subjects begin the
      affective experience by pressing a key. In this experiment, participants had to
      alternatively press two keys to concomitantly display positive, negative,
      neutral, and scrambled images extracted from the International Affective Pictures
      System (IAPS). Each key press corresponded to a specific emotional category, and
      the experimenter communicated the coupling before each trial so that the subjects
      always knew the valence of the forthcoming picture. The main results of the
      present study included a bilateral positive activity in prefrontal areas during
      expectancy of more arousing pictures (positive and negative) and an early and
      sustained positivity over occipital areas, especially during negative expectancy.
      In addition, we observed more pronounced and anteriorly distributed Late Positive
      Potential (LPPs) components in the emotional conditions. In conclusion, these
      results show that emotional expectancy can influence brain activity in both motor
      preparation and stimulus perception, suggesting enhanced pre-processing in the to
      be-stimulated areas. We propose that before a predictable emotional stimulus,
      both appetitive and defensive motivational systems act to facilitate the
      forthcoming processing of survival-relevant contents by means of an enhancement
      of attention toward more arousing pictures. 

PMID- 24904345
TI  - Near-death experiences in non-life-threatening events and coma of different
      etiologies.
AB  - BACKGROUND: Near death experiences (NDEs) are increasingly being reported as a
      clearly identifiable physiological and psychological reality of clinical
      significance. However, the definition and causes of the phenomenon as well as the
      identification of NDE experiencers is still a matter of debate. To date, the most
      widely used standardized tool to identify and characterize NDEs in research is
      the Greyson NDE scale. Using this scale, retrospective and prospective studies
      have been trying to estimate their incidence in various populations but few
      studies have attempted to associate the experiences' intensity and content to
      etiology. METHODS: This retrospective investigation assessed the intensity and
      the most frequently recounted features of self-reported NDEs after a non-life
      threatening event (i.e., "NDE-like" experience) or after a pathological coma
      (i.e., "real NDE") and according to the etiology of the acute brain insult. We
      also compared our retrospectively acquired data in anoxic coma with historical
      data from the published literature on prospective post-anoxic studies using the
      Greyson NDE scale. RESULTS: From our 190 reports who met the criteria for NDE
      (i.e., Greyson NDE scale total score >7/32), intensity (i.e., Greyson NDE scale
      total score) and content (i.e., Greyson NDE scale features) did not differ
      between "NDE-like" (n = 50) and "real NDE" (n = 140) groups, nor within the "real
      NDE" group depending on the cause of coma (anoxic/traumatic/other). The most
      frequently reported feature was peacefulness (89-93%). Only 2 patients (1%)
      recounted a negative experience. The overall NDE core features' frequencies were
      higher in our retrospective anoxic cohort when compared to historical published
      prospective data. CONCLUSIONS: It appears that "real NDEs" after coma of
      different etiologies are similar to "NDE-like" experiences occurring after non
      life threatening events. Subjects reporting NDEs retrospectively tend to have
      experienced a different content compared to the prospective experiencers.

PMID- 24904346
TI  - The effects of psilocybin and MDMA on between-network resting state functional
      connectivity in healthy volunteers.
AB  - Perturbing a system and observing the consequences is a classic scientific
      strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness
      in a marked and novel way and thus are powerful tools for studying its
      mechanisms. In the present analysis, we measured changes in resting-state
      functional connectivity (RSFC) between a standard template of different
      independent components analysis (ICA)-derived resting state networks (RSNs) under
      the influence of two different psychoactive drugs, the stimulant/psychedelic
      hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo
      controlled designs and produced marked subjective effects, although reports of
      more profound changes in consciousness were given after psilocybin. Between
      network RSFC was generally increased under psilocybin, implying that networks
      become less differentiated from each other in the psychedelic state. Decreased
      RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably
      less marked effect on between-network RSFC, implying that the extensive changes
      observed under psilocybin may be exclusive to classic psychedelic drugs and
      related to their especially profound effects on consciousness. The novel
      analytical approach applied here may be applied to other altered states of
      consciousness to improve our characterization of different conscious states and
      ultimately advance our understanding of the brain mechanisms underlying them. 

PMID- 24904347
TI  - Big data, open science and the brain: lessons learned from genomics.
AB  - The BRAIN Initiative aims to break new ground in the scale and speed of data
      collection in neuroscience, requiring tools to handle data in the magnitude of
      yottabytes (10(24)). The scale, investment and organization of it are being
      compared to the Human Genome Project (HGP), which has exemplified "big science"
      for biology. In line with the trend towards Big Data in genomic research, the
      promise of the BRAIN Initiative, as well as the European Human Brain Project,
      rests on the possibility to amass vast quantities of data to model the complex
      interactions between the brain and behavior and inform the diagnosis and
      prevention of neurological disorders and psychiatric disease. Advocates of this
      "data driven" paradigm in neuroscience argue that harnessing the large quantities
      of data generated across laboratories worldwide has numerous methodological,
      ethical and economic advantages, but it requires the neuroscience community to
      adopt a culture of data sharing and open access to benefit from them. In this
      article, we examine the rationale for data sharing among advocates and briefly
      exemplify these in terms of new "open neuroscience" projects. Then, drawing on
      the frequently invoked model of data sharing in genomics, we go on to demonstrate
      the complexities of data sharing, shedding light on the sociological and ethical
      challenges within the realms of institutions, researchers and participants,
      namely dilemmas around public/private interests in data, (lack of) motivation to
      share in the academic community, and potential loss of participant anonymity. Our
      paper serves to highlight some foreseeable tensions around data sharing relevant
      to the emergent "open neuroscience" movement. 

PMID- 24904349
TI  - Influences of semantic and syntactic incongruence on readiness potential in turn
      end anticipation.
AB  - Knowing when it is convenient to take a turn in a conversation is an important
      task for dialog partners. As it appears that this decision is made before the
      transition point has been reached, it seems to involve anticipation. There are a
      variety of studies in the literature that provide possible explanations for turn
      end anticipation. This study particularly focuses on how turn-end anticipation
      relies on syntactic and/or semantic information during utterance processing, as
      tested with syntactically and semantically violated sentences. With a combination
      reaction time and EEG experiment, we used the onset latencies of the readiness
      potential (RP) to uncover possible differences in response preparation. Although
      the mean anticipation timing accuracy (ATA) values of the behavioral test were
      all within a similar time range (control sentences: 108 ms, syntactically
      violated sentences: 93 ms and semantically violated sentences: 116 ms), we found
      evidence that response preparation is indeed different for syntactically and
      semantically violated sentences in comparison with control sentences. Our
      preconscious EEG data, in the form of RP results, indicated a response
      preparation onset to sentence end interval of 1452 ms in normal sentences, 937 ms
      in sentences with syntactic violations and 944 ms in sentences with semantic
      violations. Compared with control sentences, these intervals resulted in a
      significant RP interruption for both sentence types and indicate an interruption
      of preconscious response preparation. However, the behavioral response to
      sentence types occurred at comparable time points. 

PMID- 24904350
TI  - Consumer neuroscience to inform consumers-physiological methods to identify
      attitude formation related to over-consumption and environmental damage.

PMID- 24904348
TI  - Evidence for evolutionary specialization in human limbic structures.
AB  - Increasingly, functional and evolutionary research has highlighted the important
      contribution emotion processing makes to complex human social cognition. As such,
      it may be asked whether neural structures involved in emotion processing,
      commonly referred to as limbic structures, have been impacted in human brain
      evolution. To address this question, we performed an extensive evolutionary
      analysis of multiple limbic structures using modern phylogenetic tools. For this
      analysis, we combined new volumetric data for the hominoid (human and ape)
      amygdala and 4 amygdaloid nuclei, hippocampus, and striatum, collected using
      stereological methods in complete histological series, with previously published
      datasets on the amygdala, orbital and medial frontal cortex, and insula, as well
      as a non-limbic structure, the dorsal frontal cortex, for contrast. We performed
      a parallel analysis using large published datasets including many anthropoid
      species (human, ape, and monkey), but fewer hominoids, for the amygdala and 2
      amygdaloid subdivisions, hippocampus, schizocortex, striatum, and septal nuclei.
      To address evolutionary change, we compared observed human values to values
      predicted from regressions run through (a) non-human hominoids and (b) non-human
      anthropoids, assessing phylogenetic influence using phylogenetic generalized
      least squares regression. Compared with other hominoids, the volumes of the
      hippocampus, the lateral nucleus of the amygdala, and the orbital frontal cortex
      were, respectively, 50, 37, and 11% greater in humans than predicted for an ape
      of human hemisphere volume, while the medial and dorsal frontal cortex were,
      respectively, 26 and 29% significantly smaller. Compared with other anthropoids,
      only human values for the striatum fell significantly below predicted values.
      Overall, the data present support for the idea that regions involved in emotion
      processing are not necessarily conserved or regressive, but may even be enhanced
      in recent human evolution. 

PMID- 24904351
TI  - The relation between structural and functional connectivity depends on age and on
      task goals.
AB  - The last decade has seen an increase in neuroimaging studies examining structural
      (i.e., structural integrity of white matter tracts) and functional connectivity
      (e.g., correlations in neural activity throughout the brain). Although structural
      and functional connectivity changes have often been measured independently,
      examining the relation between these two measures is critical to understanding
      the specific function of neural networks and the ways they may differ across
      tasks and individuals. The current study addressed this question by examining the
      effect of age (treated as a continuous variable) and emotional valence on the
      relation between functional and structural connectivity. As prior studies have
      suggested that prefrontal regions may guide and regulate emotional memory search
      via functional connections with the amygdala, the current analysis focused on
      functional connectivity between the left amygdala and the left prefrontal cortex,
      and structural integrity of the uncinate fasciculus, a white matter tract
      connecting prefrontal and temporal regions. Participants took part in a scanned
      retrieval task in which they recalled positive, negative, and neutral images
      associated with neutral titles. Aging was associated with a significant increase
      in the relation between measures of structural integrity (specifically,
      fractional anisotropy, or FA) along the uncinate fasciculus and functional
      connectivity between the left ventral prefrontal cortex and amygdala during
      positive event retrieval, but not negative or neutral retrieval. Notably, during
      negative event retrieval, age was linked to stronger structure-function relations
      between the amygdala and the dorsal anterior cingulate cortex, such that
      increased structural integrity predicted stronger negative functional
      connectivity in older adults only. These findings suggest that young and older
      adults may utilize a structural pathway to engage different retrieval and
      regulatory strategies, even when structural integrity along that pathway does not
      differ. 

PMID- 24904352
TI  - Interaction between perceptual and cognitive processing well acknowledged in
      perceptual expertise research.

PMID- 24904355
TI  - The role of consciousness in triggering intellectual habits.

PMID- 24904354
TI  - Cortical entrainment to continuous speech: functional roles and interpretations.
AB  - Auditory cortical activity is entrained to the temporal envelope of speech, which
      corresponds to the syllabic rhythm of speech. Such entrained cortical activity
      can be measured from subjects naturally listening to sentences or spoken
      passages, providing a reliable neural marker of online speech processing. A
      central question still remains to be answered about whether cortical entrained
      activity is more closely related to speech perception or non-speech-specific
      auditory encoding. Here, we review a few hypotheses about the functional roles of
      cortical entrainment to speech, e.g., encoding acoustic features, parsing
      syllabic boundaries, and selecting sensory information in complex listening
      environments. It is likely that speech entrainment is not a homogeneous response
      and these hypotheses apply separately for speech entrainment generated from
      different neural sources. The relationship between entrained activity and speech
      intelligibility is also discussed. A tentative conclusion is that theta-band
      entrainment (4-8 Hz) encodes speech features critical for intelligibility while
      delta-band entrainment (1-4 Hz) is related to the perceived, non-speech-specific
      acoustic rhythm. To further understand the functional properties of speech
      entrainment, a splitter's approach will be needed to investigate (1) not just the
      temporal envelope but what specific acoustic features are encoded and (2) not
      just speech intelligibility but what specific psycholinguistic processes are
      encoded by entrained cortical activity. Similarly, the anatomical and spectro
      temporal details of entrained activity need to be taken into account when
      investigating its functional properties. 

PMID- 24904353
TI  - The social brain meets the reactive genome: neuroscience, epigenetics and the new
      social biology.
AB  - The rise of molecular epigenetics over the last few years promises to bring the
      discourse about the sociality and susceptibility to environmental influences of
      the brain to an entirely new level. Epigenetics deals with molecular mechanisms
      such as gene expression, which may embed in the organism "memories" of social
      experiences and environmental exposures. These changes in gene expression may be
      transmitted across generations without changes in the DNA sequence. Epigenetics
      is the most advanced example of the new postgenomic and context-dependent view of
      the gene that is making its way into contemporary biology. In my article I will
      use the current emergence of epigenetics and its link with neuroscience research
      as an example of the new, and in a way unprecedented, sociality of contemporary
      biology. After a review of the most important developments of epigenetic
      research, and some of its links with neuroscience, in the second part I reflect
      on the novel challenges that epigenetics presents for the social sciences for a
      re-conceptualization of the link between the biological and the social in a
      postgenomic age. Although epigenetics remains a contested, hyped, and often
      uncritical terrain, I claim that especially when conceptualized in broader non
      genecentric frameworks, it has a genuine potential to reformulate the ossified
      biology/society debate. 

PMID- 24904356
TI  - Age, dyslexia subtype and comorbidity modulate rapid auditory processing in
      developmental dyslexia.
AB  - The nature of Rapid Auditory Processing (RAP) deficits in dyslexia remains
      debated, together with the specificity of the problem to certain types of stimuli
      and/or restricted subgroups of individuals. Following the hypothesis that the
      heterogeneity of the dyslexic population may have led to contrasting results, the
      aim of the study was to define the effect of age, dyslexia subtype and
      comorbidity on the discrimination and reproduction of non-verbal tone sequences.
      Participants were 46 children aged 8-14 (26 with dyslexia, subdivided according
      to age, presence of a previous language delay, and type of dyslexia).
      Experimental tasks were a Temporal Order Judgment (TOJ) (manipulating tone
      length, ISI and sequence length), and a Pattern Discrimination Task. Dyslexic
      children showed general RAP deficits. Tone length and ISI influenced dyslexic and
      control children's performance in a similar way, but dyslexic children were more
      affected by an increase from 2 to 5 sounds. As to age, older dyslexic children's
      difficulty in reproducing sequences of 4 and 5 tones was similar to that of
      normally reading younger (but not older) children. In the analysis of subgroup
      profiles, the crucial variable appears to be the advantage, or lack thereof, in
      processing long vs. short sounds. Dyslexic children with a previous language
      delay obtained the lowest scores in RAP measures, but they performed worse with
      shorter stimuli, similar to control children, while dyslexic-only children showed
      no advantage for longer stimuli. As to dyslexia subtype, only surface dyslexics
      improved their performance with longer stimuli, while phonological dyslexics did
      not. Differential scores for short vs. long tones and for long vs. short ISIs
      predict non-word and word reading, respectively, and the former correlate with
      phonemic awareness. In conclusion, the relationship between non-verbal RAP,
      phonemic skills and reading abilities appears to be characterized by complex
      interactions with subgroup characteristics. 

PMID- 24904357
TI  - A case for neuroscience in mathematics education.

PMID- 24904358
TI  - Music-supported motor training after stroke reveals no superiority of
      synchronization in group therapy.
AB  - BACKGROUND: Music-supported therapy has been shown to be an effective tool for
      rehabilitation of motor deficits after stroke. A unique feature of music
      performance is that it is inherently social: music can be played together in
      synchrony. AIM: The present study explored the potential of synchronized music
      playing during therapy, asking whether synchronized playing could improve fine
      motor rehabilitation and mood. METHOD: Twenty-eight patients in neurological
      early rehabilitation after stroke with no substantial previous musical training
      were included. Patients learned to play simple finger exercises and familiar
      children's songs on the piano for 10 sessions of half an hour. Patients first
      received three individual therapy sessions and then continued in pairs. The
      patient pairs were divided into two groups. Patients in one group played
      synchronously (together group) whereas the patients in the other group played one
      after the other (in-turn group). To assess fine motor skill recovery the patients
      performed standard clinical tests such as the nine-hole-pegboard test (9HPT) and
      index finger-tapping speed and regularity, and metronome-paced finger tapping.
      Patients' mood was established using the Profile of Mood States (POMS). RESULTS:
      Both groups showed improvements in fine motor control. In metronome-paced finger
      tapping, patients in both groups improved significantly. Mood tests revealed
      reductions in depression and fatigue in both groups. During therapy, patients in
      the in-turn group rated their partner as more sympathetic than the together-group
      in a visual-analog scale. CONCLUSIONS: Our results suggest that music-supported
      stroke rehabilitation can improve fine motor control and mood not only
      individually but also in patient pairs. Patients who were playing in turn rather
      than simultaneously tended to reveal greater improvement in fine motor skill. We
      speculate that patients in the former group may benefit from the opportunity to
      learn from observation.

PMID- 24904359
TI  - Audiotactile interaction can change over time in cochlear implant users.
AB  - Recent results suggest that audiotactile interactions are disturbed in cochlear
      implant (CI) users. However, further exploration regarding the factors
      responsible for such abnormal sensory processing is still required. Considering
      the temporal nature of a previously used multisensory task, it remains unclear
      whether any aberrant results were caused by the specificity of the interaction
      studied or rather if it reflects an overall abnormal interaction. Moreover,
      although duration of experience with a CI has often been linked with the recovery
      of auditory functions, its impact on multisensory performance remains uncertain.
      In the present study, we used the parchment-skin illusion, a robust illustration
      of sound-biased perception of touch based on changes in auditory frequencies, to
      investigate the specificities of audiotactile interactions in CI users. Whereas
      individuals with relatively little experience with the CI performed similarly to
      the control group, experienced CI users showed a significantly greater illusory
      percept. The overall results suggest that despite being able to ignore auditory
      distractors in a temporal audiotactile task, CI users develop to become greatly
      influenced by auditory input in a spectral audiotactile task. When considered
      with the existing body of research, these results confirm that normal sensory
      interaction processing can be compromised in CI users. 

PMID- 24904360
TI  - Methodological considerations for the neurophenomenology of dreaming: commentary
      on Windt's "Reporting dream experience".

PMID- 24904363
TI  - Delay and trace fear conditioning in a complex virtual learning environment
      neural substrates of extinction.
AB  - Extinction is an important mechanism to inhibit initially acquired fear
      responses. There is growing evidence that the ventromedial prefrontal cortex
      (vmPFC) inhibits the amygdala and therefore plays an important role in the
      extinction of delay fear conditioning. To our knowledge, there is no evidence on
      the role of the prefrontal cortex in the extinction of trace conditioning up to
      now. Thus, we compared brain structures involved in the extinction of human delay
      and trace fear conditioning in a between-subjects-design in an fMRI study.
      Participants were passively guided through a virtual environment during learning
      and extinction of conditioned fear. Two different lights served as conditioned
      stimuli (CS); as unconditioned stimulus (US) a mildly painful electric stimulus
      was delivered. In the delay conditioning group (DCG) the US was administered with
      offset of one light (CS+), whereas in the trace conditioning group (TCG) the US
      was presented 4 s after CS+ offset. Both groups showed insular and striatal
      activation during early extinction, but differed in their prefrontal activation.
      The vmPFC was mainly activated in the DCG, whereas the TCG showed activation of
      the dorsolateral prefrontal cortex (dlPFC) during extinction. These results point
      to different extinction processes in delay and trace conditioning. VmPFC
      activation during extinction of delay conditioning might reflect the inhibition
      of the fear response. In contrast, dlPFC activation during extinction of trace
      conditioning may reflect modulation of working memory processes which are
      involved in bridging the trace interval and hold information in short term
      memory. 

PMID- 24904364
TI  - Constraints are the solution, not the problem.

PMID- 24904361
TI  - Robot-assisted vs. sensory integration training in treating gait and balance
      dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
AB  - BACKGROUND: Extensive research on both healthy subjects and patients with central
      nervous damage has elucidated a crucial role of postural adjustment reactions and
      central sensory integration processes in generating and "shaping" locomotor
      function, respectively. Whether robotic-assisted gait devices might improve these
      functions in Multiple sclerosis (MS) patients is not fully investigated in
      literature. PURPOSE: The aim of this study was to compare the effectiveness of
      end-effector robot-assisted gait training (RAGT) and sensory integration balance
      training (SIBT) in improving walking and balance performance in patients with MS.
      METHODS: Twenty-two patients with MS (EDSS: 1.5-6.5) were randomly assigned to
      two groups. The RAGT group (n = 12) underwent end-effector system training. The
      SIBT group (n = 10) underwent specific balance exercises. Each patient received
      twelve 50-min treatment sessions (2 days/week). A blinded rater evaluated
      patients before and after treatment as well as 1 month post treatment. Primary
      outcomes were walking speed and Berg Balance Scale. Secondary outcomes were the
      Activities-specific Balance Confidence Scale, Sensory Organization Balance Test,
      Stabilometric Assessment, Fatigue Severity Scale, cadence, step length, single
      and double support time, Multiple Sclerosis Quality of Life-54. RESULTS: Between
      groups comparisons showed no significant differences on primary and secondary
      outcome measures over time. Within group comparisons showed significant
      improvements in both groups on the Berg Balance Scale (P = 0.001). Changes
      approaching significance were found on gait speed (P = 0.07) only in the RAGT
      group. Significant changes in balance task-related domains during standing and
      walking conditions were found in the SIBT group. CONCLUSION: Balance disorders in
      patients with MS may be ameliorated by RAGT and by SIBT.

PMID- 24904366
TI  - Notational usage modulates attention networks in binumerates.
AB  - Multicultural environments require learning multiple number notations wherein
      some are encountered more frequently than others. This leads to differences in
      exposure and consequently differences in usage between notations. We find that
      differential notational usage imposes a significant neurocognitive load on number
      processing. Despite simultaneous acquisition, twenty four adult binumerates,
      familiar with two positional writing systems namely Hindu Nagari digits and Hindu
      Arabic digits, reported significantly lower preference and usage for Nagari as
      compared to Arabic. Twenty-four participants showed significantly increased
      reaction times and reduced accuracy while performing magnitude comparison tasks
      in Nagari with respect to Arabic. Functional magnetic resonance imaging revealed
      that processing Nagari elicited significantly greater activity in number
      processing and attention networks. A direct subtraction of networks for Nagari
      and Arabic notations revealed a neural circuit comprising of bilateral Intra
      parietal Sulcus (IPS), Inferior and Mid Frontal Gyri, Fusiform Gyrus and the
      Anterior Cingulate Cortex (FDR p < 0.005). Additionally, whole brain correlation
      analysis showed that activity in the left inferior parietal region was modulated
      by task performance in Nagari. We attribute the increased activation in Nagari to
      increased task difficulty due to infrequent exposure and usage. Our results
      reiterate the role of left IPS in modulating performance in numeric tasks and
      highlight the role of the attention network for monitoring symbolic notation mode
      in binumerates. 

PMID- 24904367
TI  - Investigating bottom-up auditory attention.
AB  - Bottom-up attention is a sensory-driven selection mechanism that directs
      perception toward a subset of the stimulus that is considered salient, or
      attention-grabbing. Most studies of bottom-up auditory attention have adapted
      frameworks similar to visual attention models whereby local or global "contrast"
      is a central concept in defining salient elements in a scene. In the current
      study, we take a more fundamental approach to modeling auditory attention;
      providing the first examination of the space of auditory saliency spanning pitch,
      intensity and timbre; and shedding light on complex interactions among these
      features. Informed by psychoacoustic results, we develop a computational model of
      auditory saliency implementing a novel attentional framework, guided by processes
      hypothesized to take place in the auditory pathway. In particular, the model
      tests the hypothesis that perception tracks the evolution of sound events in a
      multidimensional feature space, and flags any deviation from background
      statistics as salient. Predictions from the model corroborate the relationship
      between bottom-up auditory attention and statistical inference, and argues for a
      potential role of predictive coding as mechanism for saliency detection in
      acoustic scenes. 

PMID- 24904365
TI  - Enhanced corticomuscular coherence by external stochastic noise.
AB  - Noise can have beneficial effects as shown by the stochastic resonance (SR)
      phenomenon which is characterized by performance improvement when an optimal
      noise is added. Modern attempts to improve human performance utilize this
      phenomenon. The purpose of the present study was to investigate whether
      performance improvement by addition of optimum noise (ON) is related to increased
      cortical motor spectral power (SP) and increased corticomuscular coherence. Eight
      subjects performed a visuomotor task requiring to compensate with the right index
      finger a static force (SF) generated by a manipulandum on which Gaussian noise
      was applied. The finger position was displayed on-line on a monitor as a small
      white dot which the subjects had to maintain in the center of a green bigger
      circle. Electroencephalogram from the contralateral motor area, electromyogram
      from active muscles and finger position were recorded. The performance was
      measured by the mean absolute deviation (MAD) of the white dot from the zero
      position. ON compared to the zero noise condition induced an improvement in motor
      accuracy together with an enhancement of cortical motor SP and corticomuscular
      coherence in beta-range. These data suggest that the improved sensorimotor
      performance via SR is consistent with an increase in the cortical motor SP and in
      the corticomuscular coherence. 

PMID- 24904368
TI  - Mental representation and motor imagery training.
AB  - Research in sports, dance and rehabilitation has shown that basic action concepts
      (BACs) are fundamental building blocks of mental action representations. BACs are
      based on chunked body postures related to common functions for realizing action
      goals. In this paper, we outline issues in research methodology and an
      experimental method, the structural dimensional analysis of mental representation
      (SDA-M), to assess action-relevant representational structures that reflect the
      organization of BACs. The SDA-M reveals a strong relationship between cognitive
      representation and performance if complex actions are performed. We show how the
      SDA-M can improve motor imagery training and how it contributes to our
      understanding of coaching processes. The SDA-M capitalizes on the objective
      measurement of individual mental movement representations before training and the
      integration of these results into the motor imagery training. Such motor imagery
      training based on mental representations (MTMR) has been applied successfully in
      professional sports such as golf, volleyball, gymnastics, windsurfing, and
      recently in the rehabilitation of patients who have suffered a stroke. 

PMID- 24904369
TI  - Ten years of inhibition revisited.

PMID- 24904370
TI  - Habits: bridging the gap between personhood and personal identity.
AB  - In philosophy, the criteria for personhood (PH) at a specific point in time
      (synchronic), and the necessary and sufficient conditions of personal identity
      (PI) over time (diachronic) are traditionally separated. Hence, the transition
      between both timescales of a person's life remains largely unclear. Personal
      habits reflect a decision-making (DM) process that binds together synchronic and
      diachronic timescales. Despite the fact that the actualization of habits takes
      place synchronically, they presuppose, for the possibility of their generation,
      time in a diachronic sense. The acquisition of habits therefore rests upon PI
      over time; that is, the temporal extension of personal decisions is the necessary
      condition for the possible development of habits. Conceptually, habits can thus
      be seen as a bridge between synchronic and diachronic timescales of a person's
      life. In order to investigate the empirical mediation of this temporal linkage,
      we draw upon the neuronal mechanisms underlying DM; in particular on the
      distinction between internally and externally guided DM. Externally guided DM
      relies on external criteria at a specific point in time (synchronic); on a neural
      level, this has been associated with lateral frontal and parietal brain regions.
      In contrast, internally guided DM is based on the person's own preferences that
      involve a more longitudinal and thus diachronic timescale, which has been
      associated with the brain's intrinsic activity. Habits can be considered to
      reflect a balance between internally and externally guided DM, which implicates a
      particular temporal balance between diachronic and synchronic elements, thus
      linking two different timescales. Based on such evidence, we suggest a habit
      based neurophilosophical approach of PH and PI by focusing on the empirically
      based linkage between the synchronic and diachronic elements of habits. By doing
      so, we propose to link together what philosophically has been described and
      analyzed separately as PH and PI. 

PMID- 24904372
TI  - We should have seen this coming.

PMID- 24904371
TI  - Spatial and temporal attention in developmental dyslexia.
AB  - Although the dominant view posits that developmental dyslexia (DD) arises from a
      deficit in phonological processing, emerging evidence suggest that DD could
      result from a more basic cross-modal letter-to-speech sound integration deficit.
      Letters have to be precisely selected from irrelevant and cluttering letters by
      rapid orienting of visual attention before the correct letter-to-speech sound
      integration applies. In the present study the time-course of spatial attention
      was investigated measuring target detection reaction times (RTs) in a cuing
      paradigm, while temporal attention was investigated by assessing impaired
      identification of the first of two sequentially presented masked visual objects.
      Spatial and temporal attention were slower in dyslexic children with a deficit in
      pseudoword reading (N = 14) compared to chronological age (N = 43) and to
      dyslexics without a deficit in pseudoword reading (N = 18), suggesting a direct
      link between visual attention efficiency and phonological decoding skills.
      Individual differences in these visual attention mechanisms were specifically
      related to pseudoword reading accuracy in dyslexics. The role of spatial and
      temporal attention in the graphemic parsing process might be related to a basic
      oscillatory "temporal sampling" dysfunction. 

PMID- 24904373
TI  - Mirror neuron activity is no proof for action understanding.

PMID- 24904375
TI  - Motor modules of human locomotion: influence of EMG averaging, concatenation, and
      number of step cycles.
AB  - Locomotion can be investigated by factorization of electromyographic (EMG)
      signals, e.g., with non-negative matrix factorization (NMF). This approach is a
      convenient concise representation of muscle activities as distributed in motor
      modules, activated in specific gait phases. For applying NMF, the EMG signals are
      analyzed either as single trials, or as averaged EMG, or as concatenated EMG
      (data structure). The aim of this study is to investigate the influence of the
      data structure on the extracted motor modules. Twelve healthy men walked at their
      preferred speed on a treadmill while surface EMG signals were recorded for 60s
      from 10 lower limb muscles. Motor modules representing relative weightings of
      synergistic muscle activations were extracted by NMF from 40 step cycles
      separately (EMGSNG), from averaging 2, 3, 5, 10, 20, and 40 consecutive cycles
      (EMGAVR), and from the concatenation of the same sets of consecutive cycles
      (EMGCNC). Five motor modules were sufficient to reconstruct the original EMG
      datasets (reconstruction quality >90%), regardless of the type of data structure
      used. However, EMGCNC was associated with a slightly reduced reconstruction
      quality with respect to EMGAVR. Most motor modules were similar when extracted
      from different data structures (similarity >0.85). However, the quality of the
      reconstructed 40-step EMGCNC datasets when using the muscle weightings from
      EMGAVR was low (reconstruction quality ~40%). On the other hand, the use of
      weightings from EMGCNC for reconstructing this long period of locomotion provided
      higher quality, especially using 20 concatenated steps (reconstruction quality
      ~80%). Although EMGSNG and EMGAVR showed a higher reconstruction quality for
      short signal intervals, these data structures did not account for step-to-step
      variability. The results of this study provide practical guidelines on the
      methodological aspects of synergistic muscle activation extraction from EMG
      during locomotion. 

PMID- 24904374
TI  - Accurate expectancies diminish perceptual distraction during visual search.
AB  - The load theory of visual attention proposes that efficient selective perceptual
      processing of task-relevant information during search is determined automatically
      by the perceptual demands of the display. If the perceptual demands required to
      process task-relevant information are not enough to consume all available
      capacity, then the remaining capacity automatically and exhaustively "spills
      over" to task-irrelevant information. The spill-over of perceptual processing
      capacity increases the likelihood that task-irrelevant information will impair
      performance. In two visual search experiments, we tested the automaticity of the
      allocation of perceptual processing resources by measuring the extent to which
      the processing of task-irrelevant distracting stimuli was modulated by both
      perceptual load and top-down expectations using behavior, functional magnetic
      resonance imaging, and electrophysiology. Expectations were generated using a
      trial-by-trial cue that provided information about the likely load of the
      upcoming visual search task. When the cues were valid, behavioral interference
      was eliminated and the influence of load on frontoparietal and visual cortical
      responses was attenuated relative to when the cues were invalid. In conditions in
      which task-irrelevant information interfered with performance and modulated
      visual activity, individual differences in mean blood oxygenation level dependent
      responses measured from the left intraparietal sulcus were negatively correlated
      with individual differences in the severity of distraction. These results are
      consistent with the interpretation that a top-down biasing mechanism interacts
      with perceptual load to support filtering of task-irrelevant information. 

PMID- 24904376
TI  - Critical neuroscience-or critical science? A perspective on the perceived
      normative significance of neuroscience.
AB  - Members of the Critical Neuroscience initiative raised the question whether the
      perceived normative significance of neuroscience is justified by the discipline's
      actual possibilities. In this paper I show how brain research was assigned the
      ultimate political, social, and moral authority by some leading researchers who
      suggested that neuroscientists should change their research priorities, promising
      solutions to social challenges in order to increase research funds. Discussing
      the two examples of cognitive enhancement and the neuroscience of (im)moral
      behavior I argue that there is indeed a gap between promises and expectations on
      the one hand and knowledge and applications on the other. However it would be
      premature to generalize this to the neurosciences at large, whose knowledge
      producing, innovative, and economic potentials have just recently been confirmed
      by political and scientific decision-makers with the financial support for the
      Human Brain Project and the BRAIN Initiative. Finally, I discuss two explanations
      for the analyzed communication patterns and argue why Critical Neuroscience is
      necessary, but not sufficient. A more general Critical Science movement is
      required to improve the scientific incentive system. 

PMID- 24904377
TI  - Encoding cortical dynamics in sparse features.
AB  - Distributed cortical solutions of magnetoencephalography (MEG) and
      electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The
      extraction of patterns of interest and dynamic features from these cortical
      signals has so far relied on the expertise of investigators. There is a definite
      need in both clinical and neuroscience research for a method that will extract
      critical features from high-dimensional neuroimaging data in an automatic
      fashion. We have previously demonstrated the use of optical flow techniques for
      evaluating the kinematic properties of motion field projected on non-flat
      manifolds like in a cortical surface. We have further extended this framework to
      automatically detect features in the optical flow vector field by using the
      modified and extended 2-Riemannian Helmholtz-Hodge decomposition (HHD). Here, we
      applied these mathematical models on simulation and MEG data recorded from a
      healthy individual during a somatosensory experiment and an epilepsy pediatric
      patient during sleep. We tested whether our technique can automatically extract
      salient dynamical features of cortical activity. Simulation results indicated
      that we can precisely reproduce the simulated cortical dynamics with HHD; encode
      them in sparse features and represent the propagation of brain activity between
      distinct cortical areas. Using HHD, we decoded the somatosensory N20 component
      into two HHD features and represented the dynamics of brain activity as a
      traveling source between two primary somatosensory regions. In the epilepsy
      patient, we displayed the propagation of the epileptic activity around the
      margins of a brain lesion. Our findings indicate that HHD measures computed from
      cortical dynamics can: (i) quantitatively access the cortical dynamics in both
      healthy and disease brain in terms of sparse features and dynamic brain activity
      propagation between distinct cortical areas, and (ii) facilitate a reproducible,
      automated analysis of experimental and clinical MEG/EEG source imaging data. 

PMID- 24904378
TI  - The neural basis of task switching changes with skill acquisition.
AB  - Learning novel skills involves reorganization and optimization of cognitive
      processing involving a broad network of brain regions. Previous work has shown
      asymmetric costs of switching to a well-trained task vs. a poorly-trained task,
      but the neural basis of these differential switch costs is unclear. The current
      study examined the neural signature of task switching in the context of
      acquisition of new skill. Human participants alternated randomly between a novel
      visual task (mirror-reversed word reading) and a highly practiced one (plain word
      reading), allowing the isolation of task switching and skill set maintenance. Two
      scan sessions were separated by 2 weeks, with behavioral training on the mirror
      reading task in between the two sessions. Broad cortical regions, including
      bilateral prefrontal, parietal, and extrastriate cortices, showed decreased
      activity associated with learning of the mirror reading skill. In contrast,
      learning to switch to the novel skill was associated with decreased activity in a
      focal subcortical region in the dorsal striatum. Switching to the highly
      practiced task was associated with a non-overlapping set of regions, suggesting
      substantial differences in the neural substrates of switching as a function of
      task skill. Searchlight multivariate pattern analysis also revealed that learning
      was associated with decreased pattern information for mirror vs. plain reading
      tasks in fronto-parietal regions. Inferior frontal junction and posterior
      parietal cortex showed a joint effect of univariate activation and pattern
      information. These results suggest distinct learning mechanisms task performance
      and executive control as a function of learning. 

PMID- 24904379
TI  - Pre-dispositional constitution and plastic disposition: toward a more adequate
      descriptive framework for the notions of habits, learning and plasticity.

PMID- 24904381
TI  - Reduced procedural motor learning in deaf individuals.
AB  - Studies in the deaf suggest that cross-modal neuroplastic changes may vary across
      modalities. Only a handful of studies have examined motor capacities in the
      profoundly deaf. These studies suggest the presence of deficits in manual
      dexterity and delays in movement production. As of yet, the ability to learn
      complex sequential motor patterns has not been explored in deaf populations. The
      aim of the present study was to investigate the procedural learning skills of
      deaf adults. A serial reaction-time task (SRTT) was performed by 18 deaf subjects
      and 18 matched controls to investigate possible motor alteration subsequent to
      auditory deprivation. Deaf participants had various degrees of hearing loss. Half
      of the experimental group were early deaf adults mostly using hearing aids, the
      remaining half were late-deaf adults using a cochlear implant (CI). Participants
      carried out a repeating 12-item sequence of key presses along with random blocks
      containing no repeating sequence. Non-specific and sequence-specific learning was
      analyzed in relation to individual features related to the hearing loss. The
      results revealed significant differences between groups in sequence-specific
      learning, with deaf subjects being less efficient than controls in acquiring
      sequence-specific knowledge. We interpret the results in light of cross-modal
      plasticity and the auditory scaffolding hypothesis. 

PMID- 24904380
TI  - Precise timing when hitting falling balls.
AB  - People are extremely good at hitting falling balls with a baseball bat. Despite
      the ball's constant acceleration, they have been reported to time hits with a
      standard deviation of only about 7 ms. To examine how people achieve such
      precision, we compared performance when there were no added restrictions, with
      performance when looking with one eye, when vision was blurred, and when various
      parts of the ball's trajectory were hidden from view. We also examined how the
      size of the ball and varying the height from which it was dropped influenced
      temporal precision. Temporal precision did not become worse when vision was
      blurred, when the ball was smaller, or when balls falling from different heights
      were randomly interleaved. The disadvantage of closing one eye did not exceed
      expectations from removing one of two independent estimates. Precision was higher
      for slower balls, but only if the ball being slower meant that one saw it longer
      before the hit. It was particularly important to see the ball while swinging the
      bat. Together, these findings suggest that people time their hits so precisely by
      using the changing elevation throughout the swing to adjust the bat's movement to
      that of the ball. 

PMID- 24904382
TI  - Comparative genomics of brain size evolution.
AB  - Which genetic changes took place during mammalian, primate and human evolution to
      build a larger brain? To answer this question, one has to correlate genetic
      changes with brain size changes across a phylogeny. Such a comparative genomics
      approach provides unique information to better understand brain evolution and
      brain development. However, its statistical power is limited for example due to
      the limited number of species, the presumably complex genetics of brain size
      evolution and the large search space of mammalian genomes. Hence, it is crucial
      to add functional information, for example by limiting the search space to genes
      and regulatory elements known to play a role in the relevant cell types during
      brain development. Similarly, it is crucial to experimentally follow up on
      hypotheses generated by such a comparative approach. Recent progress in
      understanding the molecular and cellular mechanisms of mammalian brain
      development, in genome sequencing and in genome editing, promises to make a close
      integration of evolutionary and experimental methods a fruitful approach to
      better understand the genetics of mammalian brain size evolution. 

PMID- 24904384
TI  - Mind over brain, brain over mind: cognitive causes and consequences of
      controlling brain activity.

PMID- 24904383
TI  - Functional neuroanatomy of developmental dyslexia: the role of orthographic
      depth.
AB  - Orthographic depth (OD) (i.e., the complexity, consistency, or transparency of
      grapheme-phoneme correspondences in written alphabetic language) plays an
      important role in the acquisition of reading skills. Correspondingly,
      developmental dyslexia is characterized by different behavioral manifestations
      across languages varying in OD. This review focuses on the question of whether
      these different behavioral manifestations are associated with different
      functional neuroanatomical manifestations. It provides a review and critique of
      cross-linguistic brain imaging studies of developmental dyslexia. In addition, it
      includes an analysis of state-of-the-art functional neuroanatomical models of
      developmental dyslexia together with orthography-specific predictions derived
      from these models. These predictions should be tested in future brain imaging
      studies of typical and atypical reading in order to refine the current
      neurobiological understanding of developmental dyslexia, especially with respect
      to orthography-specific and universal aspects. 

PMID- 24904386
TI  - Re-engaging with the past: recapitulation of encoding operations during episodic
      retrieval.
AB  - Recollection of events is accompanied by selective reactivation of cortical
      regions which responded to specific sensory and cognitive dimensions of the
      original events. This reactivation is thought to reflect the reinstatement of
      stored memory representations and therefore to reflect memory content, but it may
      also reveal processes which support both encoding and retrieval. The present
      study used event-related functional magnetic resonance imaging to investigate
      whether regions selectively engaged in encoding face and scene context with
      studied words are also re-engaged when the context is later retrieved. As
      predicted, encoding face and scene context with visually presented words elicited
      activity in distinct, context-selective regions. Retrieval of face and scene
      context also re-engaged some of the regions which had shown successful encoding
      effects. However, this recapitulation of encoding activity did not show the same
      context selectivity observed at encoding. Successful retrieval of both face and
      scene context re-engaged regions which had been associated with encoding of the
      other type of context, as well as those associated with encoding the same type of
      context. This recapitulation may reflect retrieval attempts which are not context
      selective, but use shared retrieval cues to re-engage encoding operations in
      service of recollection. 

PMID- 24904385
TI  - Cortical alpha oscillations as a tool for auditory selective inhibition.
AB  - Listening to speech is often demanding because of signal degradations and the
      presence of distracting sounds (i.e., "noise"). The question how the brain
      achieves the task of extracting only relevant information from the mixture of
      sounds reaching the ear (i.e., "cocktail party problem") is still open. In
      analogy to recent findings in vision, we propose cortical alpha (~10 Hz)
      oscillations measurable using M/EEG as a pivotal mechanism to selectively inhibit
      the processing of noise to improve auditory selective attention to task-relevant
      signals. We review initial evidence of enhanced alpha activity in selective
      listening tasks, suggesting a significant role of alpha-modulated noise
      suppression in speech. We discuss the importance of dissociating between noise
      interference in the auditory periphery (i.e., energetic masking) and noise
      interference with more central cognitive aspects of speech processing (i.e.,
      informational masking). Finally, we point out the adverse effects of age-related
      hearing loss and/or cognitive decline on auditory selective inhibition. With this
      perspective article, we set the stage for future studies on the inhibitory role
      of alpha oscillations for speech processing in challenging listening situations. 

PMID- 24904387
TI  - Improvements to executive function during exercise training predict maintenance
      of physical activity over the following year.
AB  - Previous studies have shown that exercise training benefits cognitive, neural,
      and physical health markers in older adults. It is likely that these positive
      effects will diminish if participants return to sedentary lifestyles following
      training cessation. Theory posits that that the neurocognitive processes
      underlying self-regulation, namely executive function (EF), are important to
      maintaining positive health behaviors. Therefore, we examined whether better EF
      performance in older women would predict greater adherence to routine physical
      activity (PA) over 1 year following a 12-month resistance exercise training
      randomized controlled trial. The study sample consisted of 125 community-dwelling
      women aged 65-75 years old. Our primary outcome measure was self-reported PA, as
      measured by the Physical Activity Scale for the Elderly (PASE), assessed on a
      monthly basis from month 13 to month 25. Executive function was assessed using
      the Stroop Test at baseline (month 0) and post-training (month 12). Latent growth
      curve analyses showed that, on average, PA decreased during the follow-up period
      but at a decelerating rate. Women who made greater improvements to EF during the
      training period showed better adherence to PA during the 1-year follow-up period
      (beta = -0.36, p < 0.05); this association was unmitigated by the addition of
      covariates (beta = -0.44, p < 0.05). As expected, EF did not predict changes in
      PA during the training period (p > 0.10). Overall, these findings suggest that
      improving EF plays an important role in whether older women maintain higher
      levels of PA following exercise training and that this association is only
      apparent after training when environmental support for PA is low. 

PMID- 24904388
TI  - Lateralization of brain activation in fluent and non-fluent preschool children: a
      magnetoencephalographic study of picture-naming.
AB  - The neural causes of stuttering remain unknown. One explanation comes from
      neuroimaging studies that have reported abnormal lateralization of activation in
      the brains of people who stutter. However, these findings are generally based on
      data from adults with a long history of stuttering, raising the possibility that
      the observed lateralization anomalies are compensatory rather than causal. The
      current study investigated lateralization of brain activity in language-related
      regions of interest in young children soon after the onset of stuttering. We
      tested 24 preschool-aged children, half of whom had a positive diagnosis of
      stuttering. All children participated in a picture-naming experiment whilst their
      brain activity was recorded by magnetoencephalography. Source analysis performed
      during an epoch prior to speech onset was used to assess lateralized activation
      in three regions of interest. Activation was significantly lateralized to the
      left hemisphere in both groups and not different between groups. This study shows
      for the first time that significant speech preparatory brain activation can be
      identified in young children during picture-naming and supports the contention
      that, in stutterers, aberrant lateralization of brain function may be the result
      of neuroplastic adaptation that occurs as the condition becomes chronic. 

PMID- 24904389
TI  - Empirical neuroenchantment: from reading minds to thinking critically.
AB  - While most experts agree on the limitations of neuroimaging, the unversed public
      and indeed many a scholar-often valorizes brain imaging without heeding its
      shortcomings. Here we test the boundaries of this phenomenon, which we term
      neuroenchantment. How much are individuals ready to believe when encountering
      improbable information through the guise of neuroscience? We introduced
      participants to a crudely-built mock brain scanner, explaining that the machine
      would measure neural activity, analyze the data, and then infer the content of
      complex thoughts. Using a classic magic trick, we crafted an illusion whereby the
      imaging technology seemed to decipher the internal thoughts of participants. We
      found that most students-even undergraduates with advanced standing in
      neuroscience and psychology, who have been taught the shortcomings of
      neuroimaging-deemed such unlikely technology highly plausible. Our findings
      highlight the influence neuro-hype wields over critical thinking. 

PMID- 24904390
TI  - Nutritional influences on human neurocognitive functioning.

PMID- 24904392
TI  - Body, space, and pain.

PMID- 24904391
TI  - Imaging the where and when of tic generation and resting state networks in adult
      Tourette patients.
AB  - INTRODUCTION: Tourette syndrome (TS) is a neuropsychiatric disorder with the core
      phenomenon of tics, whose origin and temporal pattern are unclear. We
      investigated the When and Where of tic generation and resting state networks
      (RSNs) via functional magnetic resonance imaging (fMRI). METHODS: Tic-related
      activity and the underlying RSNs in adult TS were studied within one fMRI
      session. Participants were instructed to lie in the scanner and to let tics occur
      freely. Tic onset times, as determined by video-observance were used as
      regressors and added to preceding time-bins of 1 s duration each to detect prior
      activation. RSN were identified by independent component analysis (ICA) and
      correlated to disease severity by the means of dual regression. RESULTS: Two
      seconds before a tic, the supplementary motor area (SMA), ventral primary motor
      cortex, primary sensorimotor cortex and parietal operculum exhibited activation;
      1 s before a tic, the anterior cingulate, putamen, insula, amygdala, cerebellum
      and the extrastriatal-visual cortex exhibited activation; with tic-onset, the
      thalamus, central operculum, primary motor and somatosensory cortices exhibited
      activation. Analysis of resting state data resulted in 21 components including
      the so-called default-mode network. Network strength in those regions in SMA of
      two premotor ICA maps that were also active prior to tic occurrence, correlated
      significantly with disease severity according to the Yale Global Tic Severity
      Scale (YGTTS) scores. DISCUSSION: We demonstrate that the temporal pattern of tic
      generation follows the cortico-striato-thalamo-cortical circuit, and that
      cortical structures precede subcortical activation. The analysis of spontaneous
      fluctuations highlights the role of cortical premotor structures. Our study
      corroborates the notion of TS as a network disorder in which abnormal RSN
      activity might contribute to the generation of tics in SMA.

PMID- 24904393
TI  - Prefrontal control and internet addiction: a theoretical model and review of
      neuropsychological and neuroimaging findings.
AB  - Most people use the Internet as a functional tool to perform their personal goals
      in everyday-life such as making airline or hotel reservations. However, some
      individuals suffer from a loss of control over their Internet use resulting in
      personal distress, symptoms of psychological dependence, and diverse negative
      consequences. This phenomenon is often referred to as Internet addiction. Only
      Internet Gaming Disorder has been included in the appendix of the DSM-5, but it
      has already been argued that Internet addiction could also comprise problematic
      use of other applications with cybersex, online relations, shopping, and
      information search being Internet facets at risk for developing an addictive
      behavior. Neuropsychological investigations have pointed out that certain
      prefrontal functions in particular executive control functions are related to
      symptoms of Internet addiction, which is in line with recent theoretical models
      on the development and maintenance of the addictive use of the Internet. Control
      processes are particularly reduced when individuals with Internet addiction are
      confronted with Internet-related cues representing their first choice use. For
      example, processing Internet-related cues interferes with working memory
      performance and decision making. Consistent with this, results from functional
      neuroimaging and other neuropsychological studies demonstrate that cue
      reactivity, craving, and decision making are important concepts for understanding
      Internet addiction. The findings on reductions in executive control are
      consistent with other behavioral addictions, such as pathological gambling. They
      also emphasize the classification of the phenomenon as an addiction, because
      there are also several similarities with findings in substance dependency. The
      neuropsychological and neuroimaging results have important clinical impact, as
      one therapy goal should enhance control over the Internet use by modifying
      specific cognitions and Internet use expectancies. 

PMID- 24904394
TI  - Balanced neural architecture and the idling brain.
AB  - A signature feature of cortical spike trains is their trial-to-trial variability.
      This variability is large in the spontaneous state and is reduced when cortex is
      driven by a stimulus or task. Models of recurrent cortical networks with
      unstructured, yet balanced, excitation and inhibition generate variability
      consistent with evoked conditions. However, these models produce spike trains
      which lack the long timescale fluctuations and large variability exhibited during
      spontaneous cortical dynamics. We propose that global network architectures which
      support a large number of stable states (attractor networks) allow balanced
      networks to capture key features of neural variability in both spontaneous and
      evoked conditions. We illustrate this using balanced spiking networks with
      clustered assembly, feedforward chain, and ring structures. By assuming that
      global network structure is related to stimulus preference, we show that signal
      correlations are related to the magnitude of correlations in the spontaneous
      state. Finally, we contrast the impact of stimulation on the trial-to-trial
      variability in attractor networks with that of strongly coupled spiking networks
      with chaotic firing rate instabilities, recently investigated by Ostojic (2014).
      We find that only attractor networks replicate an experimentally observed
      stimulus-induced quenching of trial-to-trial variability. In total, the
      comparison of the trial-variable dynamics of single neurons or neuron pairs
      during spontaneous and evoked activity can be a window into the global structure
      of balanced cortical networks. 

PMID- 24904395
TI  - Emergence of task-dependent representations in working memory circuits.
AB  - A wealth of experimental evidence suggests that working memory circuits
      preferentially represent information that is behaviorally relevant. Still, we are
      missing a mechanistic account of how these representations come about. Here we
      provide a simple explanation for a range of experimental findings, in light of
      prefrontal circuits adapting to task constraints by reward-dependent learning. In
      particular, we model a neural network shaped by reward-modulated spike-timing
      dependent plasticity (r-STDP) and homeostatic plasticity (intrinsic excitability
      and synaptic scaling). We show that the experimentally-observed neural
      representations naturally emerge in an initially unstructured circuit as it
      learns to solve several working memory tasks. These results point to a critical,
      and previously unappreciated, role for reward-dependent learning in shaping
      prefrontal cortex activity. 

PMID- 24904397
TI  - Allen Brain Atlas-Driven Visualizations: a web-based gene expression energy
      visualization tool.
AB  - The Allen Brain Atlas-Driven Visualizations (ABADV) is a publicly accessible web
      based tool created to retrieve and visualize expression energy data from the
      Allen Brain Atlas (ABA) across multiple genes and brain structures. Though the
      ABA offers their own search engine and software for researchers to view their
      growing collection of online public data sets, including extensive gene
      expression and neuroanatomical data from human and mouse brain, many of their
      tools limit the amount of genes and brain structures researchers can view at
      once. To complement their work, ABADV generates multiple pie charts, bar charts
      and heat maps of expression energy values for any given set of genes and brain
      structures. Such a suite of free and easy-to-understand visualizations allows for
      easy comparison of gene expression across multiple brain areas. In addition, each
      visualization links back to the ABA so researchers may view a summary of the
      experimental detail. ABADV is currently supported on modern web browsers and is
      compatible with expression energy data from the Allen Mouse Brain Atlas in situ
      hybridization data. By creating this web application, researchers can immediately
      obtain and survey numerous amounts of expression energy data from the ABA, which
      they can then use to supplement their work or perform meta-analysis. In the
      future, we hope to enable ABADV across multiple data resources. 

PMID- 24904398
TI  - A simple tool for neuroimaging data sharing.
AB  - Data sharing is becoming increasingly common, but despite encouragement and
      facilitation by funding agencies, journals, and some research efforts, most
      neuroimaging data acquired today is still not shared due to political, financial,
      social, and technical barriers to sharing data that remain. In particular,
      technical solutions are few for researchers that are not a part of larger efforts
      with dedicated sharing infrastructures, and social barriers such as the time
      commitment required to share can keep data from becoming publicly available. We
      present a system for sharing neuroimaging data, designed to be simple to use and
      to provide benefit to the data provider. The system consists of a server at the
      International Neuroinformatics Coordinating Facility (INCF) and user tools for
      uploading data to the server. The primary design principle for the user tools is
      ease of use: the user identifies a directory containing Digital Imaging and
      Communications in Medicine (DICOM) data, provides their INCF Portal
      authentication, and provides identifiers for the subject and imaging session. The
      user tool anonymizes the data and sends it to the server. The server then runs
      quality control routines on the data, and the data and the quality control
      reports are made public. The user retains control of the data and may change the
      sharing policy as they need. The result is that in a few minutes of the user's
      time, DICOM data can be anonymized and made publicly available, and an initial
      quality control assessment can be performed on the data. The system is currently
      functional, and user tools and access to the public image database are available
      at http://xnat.incf.org/. 

PMID- 24904399
TI  - Web based tools for visualizing imaging data and development of XNATView, a zero
      footprint image viewer.
AB  - Advances in web technologies now allow direct visualization of imaging data sets
      without necessitating the download of large file sets or the installation of
      software. This allows centralization of file storage and facilitates image review
      and analysis. XNATView is a light framework recently developed in our lab to
      visualize DICOM images stored in The Extensible Neuroimaging Archive Toolkit
      (XNAT). It consists of a PyXNAT-based framework to wrap around the REST
      application programming interface (API) and query the data in XNAT. XNATView was
      developed to simplify quality assurance, help organize imaging data, and
      facilitate data sharing for intra- and inter-laboratory collaborations. Its zero
      footprint design allows the user to connect to XNAT from a web browser, navigate
      through projects, experiments, and subjects, and view DICOM images with
      accompanying metadata all within a single viewing instance. 

PMID- 24904400
TI  - CBRAIN: a web-based, distributed computing platform for collaborative
      neuroimaging research.
AB  - The Canadian Brain Imaging Research Platform (CBRAIN) is a web-based
      collaborative research platform developed in response to the challenges raised by
      data-heavy, compute-intensive neuroimaging research. CBRAIN offers transparent
      access to remote data sources, distributed computing sites, and an array of
      processing and visualization tools within a controlled, secure environment. Its
      web interface is accessible through any modern browser and uses graphical
      interface idioms to reduce the technical expertise required to perform large
      scale computational analyses. CBRAIN's flexible meta-scheduling has allowed the
      incorporation of a wide range of heterogeneous computing sites, currently
      including nine national research High Performance Computing (HPC) centers in
      Canada, one in Korea, one in Germany, and several local research servers. CBRAIN
      leverages remote computing cycles and facilitates resource-interoperability in a
      transparent manner for the end-user. Compared with typical grid solutions
      available, our architecture was designed to be easily extendable and deployed on
      existing remote computing sites with no tool modification, administrative
      intervention, or special software/hardware configuration. As October 2013, CBRAIN
      serves over 200 users spread across 53 cities in 17 countries. The platform is
      built as a generic framework that can accept data and analysis tools from any
      discipline. However, its current focus is primarily on neuroimaging research and
      studies of neurological diseases such as Autism, Parkinson's and Alzheimer's
      diseases, Multiple Sclerosis as well as on normal brain structure and
      development. This technical report presents the CBRAIN Platform, its current
      deployment and usage and future direction. 

PMID- 24904401
TI  - Neurovascular Network Explorer 1.0: a database of 2-photon single-vessel diameter
      measurements with MATLAB((r)) graphical user interface.
AB  - We present a database client software-Neurovascular Network Explorer 1.0 (NNE
      1.0)-that uses MATLAB((r)) based Graphical User Interface (GUI) for interaction
      with a database of 2-photon single-vessel diameter measurements from our previous
      publication (Tian et al., 2010). These data are of particular interest for
      modeling the hemodynamic response. NNE 1.0 is downloaded by the user and then
      runs either as a MATLAB script or as a standalone program on a Windows platform.
      The GUI allows browsing the database according to parameters specified by the
      user, simple manipulation and visualization of the retrieved records (such as
      averaging and peak-normalization), and export of the results. Further, we provide
      NNE 1.0 source code. With this source code, the user can database their own
      experimental results, given the appropriate data structure and naming
      conventions, and thus share their data in a user-friendly format with other
      investigators. NNE 1.0 provides an example of seamless and low-cost solution for
      sharing of experimental data by a regular size neuroscience laboratory and may
      serve as a general template, facilitating dissemination of biological results and
      accelerating data-driven modeling approaches. 

PMID- 24904403
TI  - Behavior control in the sensorimotor loop with short-term synaptic dynamics
      induced by self-regulating neurons.
AB  - The behavior and skills of living systems depend on the distributed control
      provided by specialized and highly recurrent neural networks. Learning and memory
      in these systems is mediated by a set of adaptation mechanisms, known
      collectively as neuronal plasticity. Translating principles of recurrent neural
      control and plasticity to artificial agents has seen major strides, but is
      usually hampered by the complex interactions between the agent's body and its
      environment. One of the important standing issues is for the agent to support
      multiple stable states of behavior, so that its behavioral repertoire matches the
      requirements imposed by these interactions. The agent also must have the capacity
      to switch between these states in time scales that are comparable to those by
      which sensory stimulation varies. Achieving this requires a mechanism of short
      term memory that allows the neurocontroller to keep track of the recent history
      of its input, which finds its biological counterpart in short-term synaptic
      plasticity. This issue is approached here by deriving synaptic dynamics in
      recurrent neural networks. Neurons are introduced as self-regulating units with a
      rich repertoire of dynamics. They exhibit homeostatic properties for certain
      parameter domains, which result in a set of stable states and the required short
      term memory. They can also operate as oscillators, which allow them to surpass
      the level of activity imposed by their homeostatic operation conditions. Neural
      systems endowed with the derived synaptic dynamics can be utilized for the neural
      behavior control of autonomous mobile agents. The resulting behavior depends also
      on the underlying network structure, which is either engineered or developed by
      evolutionary techniques. The effectiveness of these self-regulating units is
      demonstrated by controlling locomotion of a hexapod with 18 degrees of freedom,
      and obstacle-avoidance of a wheel-driven robot. 

PMID- 24904402
TI  - Accumulated source imaging of brain activity with both low and high-frequency
      neuromagnetic signals.
AB  - Recent studies have revealed the importance of high-frequency brain signals (>70
      Hz). One challenge of high-frequency signal analysis is that the size of time
      frequency representation of high-frequency brain signals could be larger than 1
      terabytes (TB), which is beyond the upper limits of a typical computer
      workstation's memory (<196 GB). The aim of the present study is to develop a new
      method to provide greater sensitivity in detecting high-frequency
      magnetoencephalography (MEG) signals in a single automated and versatile
      interface, rather than the more traditional, time-intensive visual inspection
      methods, which may take up to several days. To address the aim, we developed a
      new method, accumulated source imaging, defined as the volumetric summation of
      source activity over a period of time. This method analyzes signals in both low-
      (1~70 Hz) and high-frequency (70~200 Hz) ranges at source levels. To extract
      meaningful information from MEG signals at sensor space, the signals were
      decomposed to channel-cross-channel matrix (CxC) representing the spatiotemporal
      patterns of every possible sensor-pair. A new algorithm was developed and tested
      by calculating the optimal CxC and source location-orientation weights for
      volumetric source imaging, thereby minimizing multi-source interference and
      reducing computational cost. The new method was implemented in C/C++ and tested
      with MEG data recorded from clinical epilepsy patients. The results of
      experimental data demonstrated that accumulated source imaging could effectively
      summarize and visualize MEG recordings within 12.7 h by using approximately 10 GB
      of computer memory. In contrast to the conventional method of visually
      identifying multi-frequency epileptic activities that traditionally took 2-3 days
      and used 1-2 TB storage, the new approach can quantify epileptic abnormalities in
      both low- and high-frequency ranges at source levels, using much less time and
      computer memory. 

PMID- 24904404
TI  - Decoding spectrotemporal features of overt and covert speech from the human
      cortex.
AB  - Auditory perception and auditory imagery have been shown to activate overlapping
      brain regions. We hypothesized that these phenomena also share a common
      underlying neural representation. To assess this, we used electrocorticography
      intracranial recordings from epileptic patients performing an out loud or a
      silent reading task. In these tasks, short stories scrolled across a video screen
      in two conditions: subjects read the same stories both aloud (overt) and silently
      (covert). In a control condition the subject remained in a resting state. We
      first built a high gamma (70-150 Hz) neural decoding model to reconstruct
      spectrotemporal auditory features of self-generated overt speech. We then
      evaluated whether this same model could reconstruct auditory speech features in
      the covert speech condition. Two speech models were tested: a spectrogram and a
      modulation-based feature space. For the overt condition, reconstruction accuracy
      was evaluated as the correlation between original and predicted speech features,
      and was significant in each subject (p < 10(-5); paired two-sample t-test). For
      the covert speech condition, dynamic time warping was first used to realign the
      covert speech reconstruction with the corresponding original speech from the
      overt condition. Reconstruction accuracy was then evaluated as the correlation
      between original and reconstructed speech features. Covert reconstruction
      accuracy was compared to the accuracy obtained from reconstructions in the
      baseline control condition. Reconstruction accuracy for the covert condition was
      significantly better than for the control condition (p < 0.005; paired two-sample
      t-test). The superior temporal gyrus, pre- and post-central gyrus provided the
      highest reconstruction information. The relationship between overt and covert
      speech reconstruction depended on anatomy. These results provide evidence that
      auditory representations of covert speech can be reconstructed from models that
      are built from an overt speech data set, supporting a partially shared neural
      substrate. 

PMID- 24904405
TI  - Organic electrode coatings for next-generation neural interfaces.
AB  - Traditional neuronal interfaces utilize metallic electrodes which in recent years
      have reached a plateau in terms of the ability to provide safe stimulation at
      high resolution or rather with high densities of microelectrodes with improved
      spatial selectivity. To achieve higher resolution it has become clear that
      reducing the size of electrodes is required to enable higher electrode counts
      from the implant device. The limitations of interfacing electrodes including low
      charge injection limits, mechanical mismatch and foreign body response can be
      addressed through the use of organic electrode coatings which typically provide a
      softer, more roughened surface to enable both improved charge transfer and lower
      mechanical mismatch with neural tissue. Coating electrodes with conductive
      polymers or carbon nanotubes offers a substantial increase in charge transfer
      area compared to conventional platinum electrodes. These organic conductors
      provide safe electrical stimulation of tissue while avoiding undesirable chemical
      reactions and cell damage. However, the mechanical properties of conductive
      polymers are not ideal, as they are quite brittle. Hydrogel polymers present a
      versatile coating option for electrodes as they can be chemically modified to
      provide a soft and conductive scaffold. However, the in vivo chronic inflammatory
      response of these conductive hydrogels remains unknown. A more recent approach
      proposes tissue engineering the electrode interface through the use of
      encapsulated neurons within hydrogel coatings. This approach may provide a method
      for activating tissue at the cellular scale, however, several technological
      challenges must be addressed to demonstrate feasibility of this innovative idea.
      The review focuses on the various organic coatings which have been investigated
      to improve neural interface electrodes. 

PMID- 24904408
TI  - Gender-specific impact of personal health parameters on individual brain aging in
      cognitively unimpaired elderly subjects.
AB  - Aging alters brain structure and function. Personal health markers and modifiable
      lifestyle factors are related to individual brain aging as well as to the risk of
      developing Alzheimer's disease (AD). This study used a novel magnetic resonance
      imaging (MRI)-based biomarker to assess the effects of 17 health markers on
      individual brain aging in cognitively unimpaired elderly subjects. By employing
      kernel regression methods, the expression of normal brain-aging patterns forms
      the basis to estimate the brain age of a given new subject. If the estimated age
      is higher than the chronological age, a positive brain age gap estimation
      (BrainAGE) score indicates accelerated atrophy and is considered a risk factor
      for developing AD. Within this cross-sectional, multi-center study 228
      cognitively unimpaired elderly subjects (118 males) completed an MRI at 1.5Tesla,
      physiological and blood parameter assessments. The multivariate regression model
      combining all measured parameters was capable of explaining 39% of BrainAGE
      variance in males (p < 0.001) and 32% in females (p < 0.01). Furthermore, markers
      of the metabolic syndrome as well as markers of liver and kidney functions were
      profoundly related to BrainAGE scores in males (p < 0.05). In females, markers of
      liver and kidney functions as well as supply of vitamin B12 were significantly
      related to BrainAGE (p < 0.05). In conclusion, in cognitively unimpaired elderly
      subjects several clinical markers of poor health were associated with subtle
      structural changes in the brain that reflect accelerated aging, whereas
      protective effects on brain aging were observed for markers of good health.
      Additionally, the relations between individual brain aging and miscellaneous
      health markers show gender-specific patterns. The BrainAGE approach may thus
      serve as a clinically relevant biomarker for the detection of subtly abnormal
      patterns of brain aging probably preceding cognitive decline and development of
      AD. 

PMID- 24904407
TI  - The low-density lipoprotein receptor-related protein 1 and amyloid-beta clearance
      in Alzheimer's disease.
AB  - Accumulation and aggregation of amyloid-beta (Abeta) peptides in the brain
      trigger the development of progressive neurodegeneration and dementia associated
      with Alzheimer's disease (AD). Perturbation in Abeta clearance, rather than Abeta
      production, is likely the cause of sporadic, late-onset AD, which accounts for
      the majority of AD cases. Since cellular uptake and subsequent degradation
      constitute a major Abeta clearance pathway, the receptor-mediated endocytosis of
      Abeta has been intensely investigated. Among Abeta receptors, the low-density
      lipoprotein receptor-related protein 1 (LRP1) is one of the most studied
      receptors. LRP1 is a large endocytic receptor for more than 40 ligands, including
      apolipoprotein E, alpha2-macroglobulin and Abeta. Emerging in vitro and in vivo
      evidence demonstrates that LRP1 is critically involved in brain Abeta clearance.
      LRP1 is highly expressed in a variety of cell types in the brain including
      neurons, vascular cells and glial cells, where LRP1 functions to maintain brain
      homeostasis and control Abeta metabolism. LRP1-mediated endocytosis regulates
      cellular Abeta uptake by binding to Abeta either directly or indirectly through
      its co-receptors or ligands. Furthermore, LRP1 regulates several signaling
      pathways, which also likely influences Abeta endocytic pathways. In this review,
      we discuss how LRP1 regulates the brain Abeta clearance and how this unique
      endocytic receptor participates in AD pathogenesis. Understanding of the
      mechanisms underlying LRP1-mediated Abeta clearance should enable the rational
      design of novel diagnostic and therapeutic strategies for AD. 

PMID- 24904406
TI  - Caenorhabditis elegans: a model to investigate oxidative stress and metal
      dyshomeostasis in Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by progressive motor impairment
      attributed to progressive loss of dopaminergic (DAergic) neurons in the
      substantia nigra pars compacta. Additional clinical manifestations include non
      motor symptoms such as insomnia, depression, psychosis, and cognitive impairment.
      PD patients with mild cognitive impairment have an increased risk of developing
      dementia. The affected brain regions also show perturbed metal ion levels,
      primarily iron. These observations have led to speculation that metal ion
      dyshomeostasis plays a key role in the neuronal death of this disease. However,
      the mechanisms underlying this metal-associated neurodegeneration have yet to be
      completely elucidated. Mammalian models have traditionally been used to
      investigate PD pathogenesis. However, alternate animal models are also being
      adopted, bringing to bear their respective experimental advantage. The nematode,
      Caenorhabditis elegans, is one such system that has well-developed genetics, is
      amenable to transgenesis and has relatively low associated experimental costs. C.
      elegans has a well characterized neuronal network that includes a simple DAergic
      system. In this review we will discuss mechanisms thought to underlie PD and the
      use of C. elegans to investigate these processes. 

PMID- 24904410
TI  - Motor Variability during Sustained Contractions Increases with Cognitive Demand
      in Older Adults.
AB  - To expose cortical involvement in age-related changes in motor performance, we
      compared steadiness (force fluctuations) and fatigability of submaximal isometric
      contractions with the ankle dorsiflexor muscles in older and young adults and
      with varying levels of cognitive demand imposed. Sixteen young (20.4 +/- 2.1
      year: 8 men, 9 women) and 17 older adults (68.8 +/- 4.4 years: 9 men, 8 women)
      attended three sessions and performed a 40 s isometric contraction at 5% maximal
      voluntary contraction (MVC) force followed by an isometric contraction at 30% MVC
      until task failure. The cognitive demand required during the submaximal
      contractions in each session differed as follows: (1) high-cognitive demand
      session where difficult mental math was imposed (counting backward by 13 from a 4
      digit number); (2) low-cognitive demand session which involved simple mental math
      (counting backward by 1); and (3) control session with no mental math. Anxiety
      was elevated during the high-cognitive demand session compared with other
      sessions for both age groups but more so for the older adults than young adults
      (p  < 0.05). Older adults had larger force fluctuations than young adults during:
      (1) the 5% MVC task as cognitive demand increased (p  = 0.007), and (2) the
      fatiguing contraction for all sessions (p  = 0.002). Time to task failure did not
      differ between sessions or age groups (p  > 0.05), but the variability between
      sessions (standard deviation of three sessions) was greater for older adults than
      young (2.02 +/- 1.05 vs. 1.25 +/- 0.51 min, p  < 0.05). Thus, variability in
      lower limb motor performance for low- and moderate-force isometric tasks
      increased with age and was exacerbated when cognitive demand was imposed, and may
      be related to modulation of synergist and antagonist muscles and an altered
      neural strategy with age originating from central sources. These data have
      significant implications for cognitively demanding low-force motor tasks that are
      relevant to functional and ergonomic in an aging workforce. 

PMID- 24904409
TI  - Cognitive spare capacity in older adults with hearing loss.
AB  - Individual differences in working memory capacity (WMC) are associated with
      speech recognition in adverse conditions, reflecting the need to maintain and
      process speech fragments until lexical access can be achieved. When working
      memory resources are engaged in unlocking the lexicon, there is less Cognitive
      Spare Capacity (CSC) available for higher level processing of speech. CSC is
      essential for interpreting the linguistic content of speech input and preparing
      an appropriate response, that is, engaging in conversation. Previously, we
      showed, using a Cognitive Spare Capacity Test (CSCT) that in young adults with
      normal hearing, CSC was not generally related to WMC and that when CSC decreased
      in noise it could be restored by visual cues. In the present study, we
      investigated CSC in 24 older adults with age-related hearing loss, by
      administering the CSCT and a battery of cognitive tests. We found generally
      reduced CSC in older adults with hearing loss compared to the younger group in
      our previous study, probably because they had poorer cognitive skills and
      deployed them differently. Importantly, CSC was not reduced in the older group
      when listening conditions were optimal. Visual cues improved CSC more for this
      group than for the younger group in our previous study. CSC of older adults with
      hearing loss was not generally related to WMC but it was consistently related to
      episodic long term memory, suggesting that the efficiency of this processing
      bottleneck is important for executive processing of speech in this group. 

PMID- 24904411
TI  - Cognitive impairments associated with medial temporal atrophy and white matter
      hyperintensities: an MRI study in memory clinic patients.
AB  - In this retrospective study, we investigated the independent effects of white
      matter hyperintensities (WMH) and hippocampal atrophy on cognitive functions in a
      broad sample of patients seen in a memory clinic. To ensure generalizability,
      these associations were examined irrespective of diagnosis and with minimal
      exclusion criteria. Next to these independent effects, interactions between WMH
      and hippocampal atrophy were examined. Between January 2006 and September 2011 a
      total of 500 patients visited the memory clinic, 397 of whom were included.
      Magnetic resonance images of 397 patients were visually analyzed for WMH, medial
      temporal atrophy (MTA), and global atrophy. We evaluated the association of WMH
      and MTA with the following cognitive domains: global cognition, episodic memory,
      working memory, executive function and psychomotor speed. Main effects and
      interaction effects were examined by means of correlation and regression
      analyses. In the regression analyses, we controlled for potential confounding
      effects of global atrophy. The correlational results revealed that WMH were
      associated with global cognition, executive function and psychomotor speed,
      whereas a trend was found for episodic memory. MTA was associated with all these
      four cognitive domains; an additional trend was observed for working memory.
      Hierarchical regression analyses revealed main independent effects of MTA for
      episodic memory, executive function, psychomotor speed and global cognition; WMH
      were only associated with global cognition. The interaction between MTA and WMH
      was significant for episodic memory only. This study demonstrates that
      predominantly MTA is an independent predictor not only for memory function, with
      which is it classically associated, but also for global cognition and executive
      function. Taken together, MTA may be an important correlate of cognitive deficits
      found in people attending the memory clinic. 

PMID- 24904413
TI  - Impairment of vocal expression of negative emotions in patients with Alzheimer's
      disease.
AB  - Vocal expression of emotions (EE) in retrieval of events from autobiographical
      memory was investigated in patients in early stages of Alzheimer's disease (AD).
      Twenty-one AD patients and 19 controls were interviewed, and EE of the reported
      memories was rated by 8 independent evaluators. The AD group had lower EE of both
      recent and remote memory than controls, although EE in remote memories was better
      preserved in both groups. We observed positive correlations between EE and
      indicators of cognitive competence in AD patients. AD Patients are impaired in
      the ability to express emotions already at early stages of the disease, and EE
      seems to deteriorate along with the progression of cognitive impairment. 

PMID- 24904412
TI  - Degeneration of neuromuscular junction in age and dystrophy.
AB  - Functional denervation is a hallmark of aging sarcopenia as well as of muscular
      dystrophy. It is thought to be a major factor reducing skeletal muscle mass,
      particularly in the case of sarcopenia. Neuromuscular junctions (NMJs) serve as
      the interface between the nervous and skeletal muscular systems, and thus they
      may receive pathophysiological input of both pre- and post-synaptic origin.
      Consequently, NMJs are good indicators of motor health on a systemic level.
      Indeed, upon sarcopenia and dystrophy, NMJs morphologically deteriorate and
      exhibit altered characteristics of primary signaling molecules, such as nicotinic
      acetylcholine receptor and agrin. Since a remarkable reversibility of these
      changes can be observed by exercise, there is significant interest in
      understanding the molecular mechanisms underlying synaptic deterioration upon
      aging and dystrophy and how synapses are reset by the aforementioned treatments.
      Here, we review the literature that describes the phenomena observed at the NMJ
      in sarcopenic and dystrophic muscle as well as to how these alterations can be
      reversed and to what extent. In a second part, the current information about
      molecular machineries underlying these processes is reported. 

PMID- 24904414
TI  - Early Brain Loss in Circuits Affected by Alzheimer's Disease is Predicted by
      Fornix Microstructure but may be Independent of Gray Matter.
AB  - In a cohort of community-recruited elderly subjects with normal cognition at
      initial evaluation, we found that baseline fornix white matter (WM)
      microstructure was significantly correlated with early volumetric longitudinal
      tissue change across a region of interest (called fornix significant ROI, fSROI),
      which overlaps circuits known to be selectively vulnerable to Alzheimer's
      dementia pathology. Other WM and gray matter regions had much weaker or non
      existent associations with longitudinal tissue change. Tissue loss in fSROI was
      in turn a significant factor in a survival model of cognitive decline, as was
      baseline fornix microstructure. These findings suggest that WM deterioration in
      the fornix and tissue loss in fSROI may be the early beginnings of posterior
      limbic circuit and default mode network degeneration. We also found that gray
      matter baseline volumes in the entorhinal cortex and hippocampus predicted
      cognitive decline in survival models. But since GM regions did not also
      significantly predict brain-tissue loss, our results may imply a view in which
      early, prodromal deterioration appears as two quasi independent processes in
      white and gray matter regions of the limbic circuit crucial to memory. 

PMID- 24904415
TI  - CD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via
      suppression of FGF-9 production in the TGF-beta1 exposed murine lung.
AB  - Pulmonary fibrosis is a difficult to treat, often fatal disease whose
      pathogenesis involves dysregulated TGF-beta1 signaling. CD4+CD25+FoxP3+
      Regulatory T cells ("Tregs") exert important effects on host tolerance and arise
      from naive CD4+ lymphocytes in response to TGF-beta1. However, the precise
      contribution of Tregs to experimentally induced murine lung fibrosis remains
      unclear. We sought to better understand the role of Tregs in this context. Using
      a model of fibrosis caused by lung specific, doxycycline inducible overexpression
      of the bioactive form of the human TGF-beta1 gene we find that Tregs accumulate
      in the lung parenchyma within 5 days of transgene activation and that this
      enhancement persists to at least 14 days. Anti-CD25 Antibody mediated depletion
      of Tregs causes increased accumulation of soluble collagen and of intrapulmonary
      CD45+Col Ialpha1 fibrocytes. These effects are accompanied by enhanced local
      concentrations of the classical inflammatory mediators CD40L, TNF-alpha, and IL
      1alpha, along with the neuroimmune molecule fibroblast growth factor 9 (FGF-9,
      also known as "glial activating factor"). FGF-9 expression localizes to
      parenchymal cells and alveolar macrophages in this model and antibody mediated
      neutralization of FGF-9 results in attenuated detection of intrapulmonary
      collagen and fibrocytes without affecting Treg quantities. These data indicate
      that CD4+CD25+FoxP3+ Tregs attenuate TGF-beta1 induced lung fibrosis and
      fibrocyte accumulation in part via suppression of FGF-9. 

PMID- 24904416
TI  - Brain tissue oxygen reactivity: clinical implications and pathophysiology.

PMID- 24904417
TI  - Mechanisms of iron metabolism in Caenorhabditis elegans.
AB  - Iron is involved in many biological processes essential for sustaining life. In
      excess, iron is toxic due to its ability to catalyze the formation of free
      radicals that damage macromolecules. Organisms have developed specialized
      mechanisms to tightly regulate iron uptake, storage and efflux. Over the past
      decades, vertebrate model organisms have led to the identification of key genes
      and pathways that regulate systemic and cellular iron metabolism. This review
      provides an overview of iron metabolism in the roundworm Caenorhabditis elegans
      and highlights recent studies on the role of hypoxia and insulin signaling in the
      regulation of iron metabolism. Given that iron, hypoxia and insulin signaling
      pathways are evolutionarily conserved, C. elegans provides a genetic model
      organism that promises to provide new insights into mechanisms regulating
      mammalian iron metabolism. 

PMID- 24904421
TI  - Quantitative phenotypic and pathway profiling guides rational drug combination
      strategies.
AB  - Advances in target-based drug discovery strategies have enabled drug discovery
      groups in academia and industry to become very effective at generating molecules
      that are potent and selective against single targets. However, it has become
      apparent from disappointing results in recent clinical trials that a major
      challenge to the development of successful targeted therapies for treating
      complex multifactorial diseases is overcoming heterogeneity in target mechanism
      among patients and inherent or acquired drug resistance. Consequently,
      reductionist target directed drug-discovery approaches are not appropriately
      tailored toward identifying and optimizing multi-targeted therapeutics or
      rational drug combinations for complex disease. In this article, we describe the
      application of emerging high-content phenotypic profiling and analysis tools to
      support robust evaluation of drug combination performance following dose-ratio
      matrix screening. We further describe how the incorporation of high-throughput
      reverse phase protein microarrays with phenotypic screening can provide rational
      drug combination hypotheses but also confirm the mechanism-of-action of novel
      drug combinations, to facilitate future preclinical and clinical development
      strategies. 

PMID- 24904420
TI  - Epidemiological associations between iron and cardiovascular disease and
      diabetes.
AB  - Disruptions in iron homeostasis are linked to a broad spectrum of chronic
      conditions including cardiovascular, malignant, metabolic, and neurodegenerative
      disease. Evidence supporting this contention derives from a variety of analytical
      approaches, ranging from molecular to population-based studies. This review
      focuses on key epidemiological studies that assess the relationship between body
      iron status and chronic diseases, with particular emphasis on atherosclerosis
      ,metabolic syndrome and diabetes. Multiple surrogates have been used to measure
      body iron status, including serum ferritin, transferrin saturation, serum iron,
      and dietary iron intake. The lack of a uniform and standardized means of
      assessing body iron status has limited the precision of epidemiological
      associations. Intervention studies using depletion of iron to alter risk have
      been conducted. Genetic and molecular techniques have helped to explicate the
      biochemistry of iron metabolism at the molecular level. Plausible explanations
      for how iron contributes to the pathogenesis of these chronic diseases are
      beginning to be elucidated. Most evidence supports the hypothesis that excess
      iron contributes to chronic disease by fostering excess production of free
      radicals. Overall, epidemiological studies, reinforced by basic science
      experiments, provide a strong line of evidence supporting the association between
      iron and elevated risk of cardiovascular disease and diabetes. In this narrative
      review we attempt to condense the information from existing literature on this
      topic. 

PMID- 24904418
TI  - Heme on innate immunity and inflammation.
AB  - Heme is an essential molecule expressed ubiquitously all through our tissues.
      Heme plays major functions in cellular physiology and metabolism as the
      prosthetic group of diverse proteins. Once released from cells and from
      hemeproteins free heme causes oxidative damage and inflammation, thus acting as a
      prototypic damage-associated molecular pattern. In this context, free heme is a
      critical component of the pathological process of sterile and infectious
      hemolytic conditions including malaria, hemolytic anemias, ischemia-reperfusion,
      and hemorrhage. The plasma scavenger proteins hemopexin and albumin reduce heme
      toxicity and are responsible for transporting free heme to intracellular
      compartments where it is catabolized by heme-oxygenase enzymes. Upon hemolysis or
      severe cellular damage the serum capacity to scavenge heme may saturate and
      increase free heme to sufficient amounts to cause tissue damage in various
      organs. The mechanism by which heme causes reactive oxygen generation, activation
      of cells of the innate immune system and cell death are not fully understood.
      Although heme can directly promote lipid peroxidation by its iron atom, heme can
      also induce reactive oxygen species generation and production of inflammatory
      mediators through the activation of selective signaling pathways. Heme activates
      innate immune cells such as macrophages and neutrophils through activation of
      innate immune receptors. The importance of these events has been demonstrated in
      infectious and non-infectious diseases models. In this review, we will discuss
      the mechanisms behind heme-induced cytotoxicity and inflammation and the
      consequences of these events on different tissues and diseases. 

PMID- 24904419
TI  - It's MORe exciting than mu: crosstalk between mu opioid receptors and
      glutamatergic transmission in the mesolimbic dopamine system.
AB  - Opioids selective for the G protein-coupled mu opioid receptor (MOR) produce
      potent analgesia and euphoria. Heroin, a synthetic opioid, is considered one of
      the most addictive substances, and the recent exponential rise in opioid
      addiction and overdose deaths has made treatment development a national public
      health priority. Existing medications (methadone, buprenorphine, and naltrexone),
      when combined with psychosocial therapies, have proven efficacy in reducing
      aspects of opioid addiction. Unfortunately, these medications have critical
      limitations including those associated with opioid agonist therapies (e.g.,
      sustained physiological dependence and opioid withdrawal leading to high relapse
      rates upon discontinuation), non-adherence to daily dosing, and non-renewal of
      monthly injection with extended-release naltrexone. Furthermore, current
      medications fail to ameliorate key aspects of addiction such as powerful
      conditioned associations that trigger relapse (e.g., cues, stress, the drug
      itself). Thus, there is a need for developing novel treatments that target neural
      processes corrupted with chronic opioid use. This requires a basic understanding
      of molecular and cellular mechanisms underlying effects of opioids on synaptic
      transmission and plasticity within reward-related neural circuits. The focus of
      this review is to discuss how crosstalk between MOR-associated G protein
      signaling and glutamatergic neurotransmission leads to immediate and long-term
      effects on emotional states (e.g., euphoria, depression) and motivated behavior
      (e.g., drug-seeking, relapse). Our goal is to integrate findings on how opioids
      modulate synaptic release of glutamate and postsynaptic transmission via alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate
      receptors in the nucleus accumbens and ventral tegmental area with the clinical
      (neurobehavioral) progression of opioid dependence, as well as to identify gaps
      in knowledge that can be addressed in future studies. 

PMID- 24904422
TI  - The therapeutic potential of antioxidants, ER chaperones, NO and H2S donors, and
      statins for treatment of preeclampsia.
AB  - Preeclampsia is a complex multifactorial disease. Placental oxidative stress, a
      result of deficient spiral artery remodeling, plays an important role in the
      pathophysiology of preeclampsia. Antiangiogenic factors secreted from malperfused
      placenta are instrumental in mediating maternal endothelial dysfunction and
      consequent symptoms of preeclampsia; the mechanism is likely to involve increased
      ET-1 secretion and reduced NO bioavailability. Therapeutic interventions so far
      remain only experimental and there is no established remedy for the treatment of
      preeclampsia. This review concentrates on the evidence for the therapeutic
      potential of antioxidants, ER chaperones, NO and H2S donors, and statins. These
      compounds display pleitropic antioxidant, anti-inflammatory, and pro-angiogenic
      effects in animal and in vitro studies. Although clinical trials on the use of
      antioxidant vitamins in pregnancy proved largely unsuccessful, the scope for
      their use still exists given the beneficial cardioprotective effects of
      antioxidant-rich Mediterranean diet, periconceptual vitamin use and the
      synergistic effect of vitamin C and L-arginine. Encouraging clinical evidence
      exists for the use of NO donors, and a clinical trial is underway testing the
      effect of statins in treatment of preeclampsia. H2S recently emerged as a novel
      therapeutic agent for cardiovascular disease, and its beneficial effects were
      also tested in animal models of preeclampsia. It is risky to prescribe any
      medication to pregnant women on a large scale, and any future therapeutic
      intervention has to be well tested and safe. Many of the compounds discussed
      could be potential candidates. 

PMID- 24904423
TI  - In vitro clinical trials: the future of cell-based profiling.
AB  - The drug discovery process classically revolves around a set of biochemical and
      cellular assays to drive potency optimization and structural-activity
      relationship models. Layered on top of these concepts is the inclusion of
      molecular features that affect final drug use, things like: bioavailability,
      toxicity, stability, solubility, formulation, route of administration, etc.
      Paradoxically, most drugs entering clinical trials are only tested in a handful
      of human genetic backgrounds before they are given to people. Here we review
      efforts and opine on the use of large scale in vitro cellular and in vivo models
      that attempt to model human disease and include diversity found in the human
      genetic population. Because hundreds to thousands of individual assays are needed
      to scratch the surface of human genetic diversity, sophisticated high throughput
      automation technologies or pooling and deconvolution strategies are required.
      Characterization of each model needs to be extensive to enable non-biased
      informatics based modeling. Such approaches will enable deep understanding of
      genetic to pharmacological response and result in new methods for patient
      stratification in the clinic. Oncology medicines and cancer genetics have been
      paving the way for these approaches and we expect to see continued expansion to
      other fields such as immunology and neuroscience. 

PMID- 24904424
TI  - Fibroblasts in fibrosis: novel roles and mediators.
AB  - Fibroblasts are the most common cell type of the connective tissues found
      throughout the body and the principal source of the extensive extracellular
      matrix (ECM) characteristic of these tissues. They are also the central mediators
      of the pathological fibrotic accumulation of ECM and the cellular proliferation
      and differentiation that occurs in response to prolonged tissue injury and
      chronic inflammation. The transformation of the fibroblast cell lineage involves
      classical developmental signaling programs and includes a surprisingly diverse
      range of precursor cell types-most notably, myofibroblasts that are the apex of
      the fibrotic phenotype. Myofibroblasts display exaggerated ECM production;
      constitutively secrete and are hypersensitive to chemical signals such as
      cytokines, chemokines, and growth factors; and are endowed with a contractile
      apparatus allowing them to manipulate the ECM fibers physically to close open
      wounds. In addition to ECM production, fibroblasts have multiple concomitant
      biological roles, such as in wound healing, inflammation, and angiogenesis, which
      are each interwoven with the process of fibrosis. We now recognize many common
      fibroblast-related features across various physiological and pathological
      protracted processes. Indeed, a new appreciation has emerged for the role of non
      cancerous fibroblast interactions with tumors in cancer progression. Although the
      predominant current clinical treatments of fibrosis involve non-specific
      immunosuppressive and anti-proliferative drugs, a variety of potential therapies
      under investigation specifically target fibroblast biology. 

PMID- 24904425
TI  - Exposure to hot and cold environmental conditions does not affect the decision
      making ability of soccer referees following an intermittent sprint protocol.
AB  - Soccer referees enforce the laws of the game and the decisions they make can
      directly affect match results. Fixtures within European competitions take place
      in climatic conditions that are often challenging (e.g., Moscow ~ -5 degrees C,
      Madrid ~30 degrees C). Effects of these temperatures on player performance are
      well-documented; however, little is known how this environmental stress may
      impair cognitive performance of soccer referees and if so, whether exercise
      exasperates this. The present study aims to investigate the effect of cold [COLD;
      -5 degrees C, 40% relative humidity (RH)], hot (HOT; 30 degrees C, 40% RH) and
      temperate (CONT; 18 degrees C, 40% RH) conditions on decision making during
      soccer specific exercise. On separate occasions within each condition, 13
      physically active males; either semi-professional referees or semi-professional
      soccer players completed three 90 min intermittent treadmill protocols that
      simulated match play, interspersed with 4 computer delivered cognitive tests to
      measure vigilance and dual task capacity. Core and skin temperature, heart rate,
      rating of perceived exertion (RPE) and thermal sensation (TS) were recorded
      throughout the protocol. There was no significant difference between conditions
      for decision making in either the dual task (interaction effects: FALSE p = 0.46;
      MISSED p = 0.72; TRACKING p = 0.22) or vigilance assessments (interaction
      effects: FALSE p = 0.31; HIT p = 0.15; MISSED p = 0.17) despite significant
      differences in measured physiological variables (skin temperature: HOT vs. CONT
      95% CI = 2.6 to 3.9, p < 0.001; HOT vs. COLD 95% CI = 6.6 to 9.0, p < 0.001; CONT
      vs. COLD 95% CI = 3.4 to 5.7, p < 0.01). It is hypothesized that the lack of
      difference observed in decision making ability between conditions was due to the
      exercise protocol used, as it may not have elicited an appropriate and valid
      soccer specific internal load to alter cognitive functioning. 

PMID- 24904427
TI  - Cardiovascular consequence of reclining vs. sitting beach-chair body position for
      induction of anesthesia.
AB  - The sitting beach-chair position is regularly used for shoulder surgery and
      anesthesia may be induced in that position. We tested the hypothesis that the
      cardiovascular challenge induced by induction of anesthesia is attenuated if the
      patient is placed in a reclining beach-chair position. Anesthesia was induced
      with propofol in the sitting beach-chair (n = 15) or with the beach-chair tilted
      backwards to a reclining beach-chair position (n = 15). The last group was
      stepwise tilted to the sitting beach-chair position prior to surgery. Hypotension
      was treated with ephedrine. Continuous hemodynamic variables were recorded by
      photoplethysmography and frontal cerebral oxygenation (ScO2) by near infrared
      spectroscopy. Significant differences were only observed immediately after the
      induction when patients induced in a reclining beach-chair position had higher
      mean arterial pressure (MAP) (35 +/- 12 vs. 45 +/- 15 % reduction from baseline,
      p = 0.04) and ScO2 (7 +/- 6 vs. 1 +/- 8% increase from baseline, p = 0.02) and
      received less ephedrine (mean: 4 vs. 13 mg, p = 0.048). The higher blood pressure
      and lower need of vasopressor following induction of anesthesia in the reclining
      compared to the sitting beach-chair position indicate more stable hemodynamics
      with the clinical implication that anesthesia should not be induced with the
      patient in the sitting position. 

PMID- 24904426
TI  - Influence of drugs on gap junctions in glioma cell lines and primary astrocytes
      in vitro.
AB  - Gap junctions (GJs) are hemichannels on cell membrane. Once they are
      intercellulary connected to the neighboring cells, they build a functional
      syncytium which allows rapid transfer of ions and molecules between cells. This
      characteristic makes GJs a potential modulator in proliferation, migration, and
      development of the cells. So far, several types of GJs are recognized on
      different brain cells as well as in glioma. Astrocytes, as one of the major cells
      that maintain neuronal homeostasis, express different types of GJs that let them
      communicate with neurons, oligodendrocytes, and endothelial cells of the blood
      brain barrier; however, the main GJ in astrocytes is connexin 43. There are
      different cerebral diseases in which astrocyte GJs might play a role. Several
      drugs have been reported to modulate gap junctional communication in the brain
      which can consequently have beneficial or detrimental effects on the course of
      treatment in certain diseases. However, the exact cellular mechanism behind those
      pharmaceutical efficacies on GJs is not well-understood. Accordingly, how
      specific drugs would affect GJs and what some consequent specific brain diseases
      would be are the interests of the authors of this chapter. We would focus on
      pharmaceutical effects on GJs on astrocytes in specific diseases where GJs could
      possibly play a role including: (1) migraine and a novel therapy for migraine
      with aura, (2) neuroautoimmune diseases and immunomodulatory drugs in the
      treatment of demyelinating diseases of the central nervous system such as
      multiple sclerosis, (3) glioma and antineoplastic and anti-inflammatory agents
      that are used in treating brain tumors, and (4) epilepsy and anticonvulsants that
      are widely used for seizures therapy. All of the above-mentioned therapeutic
      categories can possibly affect GJs expression of astrocytes and the role is
      discussed in the upcoming chapter. 

PMID- 24904428
TI  - Functional sympatholysis and sympathetic escape in a theoretical model for blood
      flow regulation.
AB  - A mathematical simulation of flow regulation in vascular networks is used to
      investigate the interaction between arteriolar vasoconstriction due to
      sympathetic nerve activity (SNA) and vasodilation due to increased oxygen demand.
      A network with 13 vessel segments in series is used, each segment representing a
      different size range of arterioles or venules. The network includes five actively
      regulating arteriolar segments with time-dependent diameters influenced by shear
      stress, wall tension, metabolic regulation, and SNA. Metabolic signals are
      assumed to be propagated upstream along vessel walls via a conducted response.
      The model exhibits functional sympatholysis, in which sympathetic
      vasoconstriction is partially abrogated by increases in metabolic demand, and
      sympathetic escape, in which SNA elicits an initial vasoconstriction followed by
      vasodilation. In accordance with experimental observations, these phenomena are
      more prominent in small arterioles than in larger arterioles when SNA is assumed
      to act equally on arterioles of all sizes. The results imply that a mechanism
      based on the competing effects on arteriolar tone of SNA and conducted metabolic
      signals can account for several observed characteristics of functional
      sympatholysis, including the different responses of large and small arterioles. 

PMID- 24904429
TI  - PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid
      modulation of voltage-dependent gating.
AB  - Voltage-gated potassium (Kv) channels contain voltage-sensing (VSD) and pore-gate
      (PGD) structural domains. During voltage-dependent gating, conformational changes
      in the two domains are coupled giving rise to voltage-dependent opening of the
      channel. In addition to membrane voltage, KCNQ (Kv7) channel opening requires the
      membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies
      suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1
      channels. In this review, we put these findings in the context of the current
      understanding of voltage-dependent gating, lipid modulation of Kv channel
      activation, and PIP2-regulation of KCNQ channels. We suggest that lipid-mediated
      coupling of functional domains is a common mechanism among KCNQ channels that may
      be applicable to other Kv channels and membrane proteins. 

PMID- 24904431
TI  - MFS multidrug transporters in pathogenic fungi: do they have real clinical
      impact?
AB  - Infections caused by opportunistic fungal pathogens have reached concerning
      numbers due to the increase of the immunocrompromised human population and to the
      development of antifungal resistance. This resistance is often attributed to the
      action of multidrug efflux pumps, belonging to the ATP-binding cassette (ABC)
      superfamily and the major facilitator superfamily (MFS). Although many studies
      have focused on the role of ABC multidrug efflux transporters, little is still
      known on the part played by the Drug:H(+) Antiporter (DHA) family of the MFS in
      this context. This review summarizes current knowledge on the role in antifungal
      drug resistance, mode of action and phylogenetic relations of DHA transporters,
      from the model yeast S. cerevisiae to pathogenic yeasts and filamentous fungi.
      Through the compilation of the predicted DHA transporters in the medically
      relevant Candida albicans, C. glabrata, C. parapsilosis, C. lusitaniae, C.
      tropicalis, C. guilliermondii, Cryptococcus neoformans, and Aspergillus fumigatus
      species, the fact that only 5% of the DHA transporters from these organisms have
      been characterized so far is evidenced. The role of these transporters in
      antifungal drug resistance and in pathogen-host interaction is described and
      their clinical relevance discussed. Given the knowledge gathered for these few
      DHA transporters, the need to carry out a systematic characterization of the DHA
      multidrug efflux pumps in fungal pathogens, with emphasis on their clinical
      relevance, is highlighted. 

PMID- 24904430
TI  - Dendritic cells in atherosclerotic inflammation: the complexity of functions and
      the peculiarities of pathophysiological effects.
AB  - Atherosclerosis is considered as a chronic disease of arterial wall, with a
      strong contribution of inflammation. Dendritic cells (DCs) play a crucial role in
      the initiation of proatherogenic inflammatory response. Mature DCs present self
      antigens thereby supporting differentiation of naive T cells to effector cells
      that further propagate atherosclerotic inflammation. Regulatory T cells (Tregs)
      can suppress proinflammatory function of mature DCs. In contrast, immature DCs
      are able to induce Tregs and prevent differentiation of naive T cells to
      proinflammatory effector T cells by initiating apoptosis and anergy in naive T
      cells. Indeed, immature DCs showed tolerogenic and anti-inflammatory properties.
      Thus, DCs play a double role in atherosclerosis: mature DCs are proatherogenic
      while immature DCs appear to be anti-atherogenic. Tolerogenic and anti
      inflammatory capacity of immature DCs can be therefore utilized for the
      development of new immunotherapeutic strategies against atherosclerosis. 

PMID- 24904432
TI  - Greater glucose uptake heterogeneity in knee muscles of old compared to young men
      during isometric contractions detected by [(18)F]-FDG PET/CT.
AB  - We used positron emission tomography/computed tomography (PET/CT) and [(18)F]-FDG
      to test the hypothesis that glucose uptake (GU) heterogeneity in skeletal muscles
      as a measure of heterogeneity in muscle activity is greater in old than young men
      when they perform isometric contractions. Six young (26 +/- 6 years) and six old
      (77 +/- 6 years) men performed two types of submaximal isometric contractions
      that required either force or position control. [(18)F]-FDG was injected during
      the task and PET/CT scans were performed immediately after the task. Within
      muscle heterogeneity of knee muscles was determined by calculating the
      coefficient of variation (CV) of GU in PET image voxels within the muscles of
      interest. The average GU heterogeneity (mean +/- SD) for knee extensors and
      flexors was greater for the old (35.3 +/- 3.3%) than the young (28.6 +/- 2.4%) (P
      = 0.006). Muscle volume of the knee extensors were greater for the young compared
      to the old men (1016 +/- 163 vs. 598 +/- 70 cm(3), P = 0.004). In a multiple
      regression model, knee extensor muscle volume was a predictor (partial r = -0.87;
      P = 0.001) of GU heterogeneity for old men (R (2) = 0.78; P < 0.001), and MVC
      force predicted GU heterogeneity for young men (partial r = -0.95, P < 0.001).
      The findings demonstrate that GU is more spatially variable for old than young
      men and especially so for old men who exhibit greater muscle atrophy. 

PMID- 24904433
TI  - Possibilities for examining the neural control of gait in humans with fNIRS.

PMID- 24904435
TI  - Implicit motivational processes underlying smoking in american and dutch
      adolescents.
AB  - INTRODUCTION: Research demonstrates that cognitive biases toward drug-related
      stimuli are correlated with substance use. This study aimed to investigate
      differences in cognitive biases (i.e., approach bias, attentional bias, and
      memory associations) between smoking and non-smoking adolescents in the US and
      the Netherlands. Within the group of smokers, we examined the relative predictive
      value of the cognitive biases and impulsivity related constructs (including
      inhibition skills, working memory, and risk taking) on daily smoking and nicotine
      dependence. METHOD: A total of 125 American and Dutch adolescent smokers (n = 67)
      and non-smokers (n = 58) between 13 and 18 years old participated. Participants
      completed the smoking approach-avoidance task, the classical and emotional Stroop
      task, brief implicit associations task, balloon analog risk task, the self
      ordering pointing task, and a questionnaire assessing level of nicotine
      dependence and smoking behavior. RESULTS: The analytical sample consisted of 56
      Dutch adolescents (27 smokers and 29 non-smokers) and 37 American adolescents (19
      smokers and 18 non-smokers). No differences in cognitive biases between smokers
      and non-smokers were found. Generally, Dutch adolescents demonstrated an
      avoidance bias toward both smoking and neutral stimuli whereas the American
      adolescents did not demonstrate a bias. Within the group of smokers, regression
      analyses showed that stronger attentional bias and weaker inhibition skills
      predicted greater nicotine dependence while weak working memory predicted more
      daily cigarette use. CONCLUSION: Attentional bias, inhibition skills, and working
      memory might be important factors explaining smoking in adolescence. Cultural
      differences in approach-avoidance bias should be considered in future research.

PMID- 24904436
TI  - Prefrontal Gray Matter and Motivation for Treatment in Cocaine-Dependent
      Individuals with and without Personality Disorders.
AB  - Addiction treatment is a long-term goal and therefore prefrontal-striatal regions
      regulating goal-directed behavior are to be associated with individual
      differences on treatment motivation. We aimed at examining the association
      between gray matter volumes in prefrontal cortices and striatum and readiness to
      change at treatment onset in cocaine users with and without personality
      disorders. Participants included 17 cocaine users without psychiatric
      comorbidities, 17 cocaine users with Cluster B disorders, and 12 cocaine users
      with Cluster C disorders. They completed the University of Rhode Island Change
      Assessment Scale, which measures four stages of treatment change
      (precontemplation, contemplation, action, and maintenance) and overall readiness
      to change, and were scanned in a 3 T MRI scanner. We defined three regions of
      interest (ROIs): the ventromedial prefrontal cortex (including medial
      orbitofrontal cortex and subgenual and rostral anterior cingulate cortex), the
      dorsomedial prefrontal cortex (i.e., superior medial frontal cortex), and the
      neostriatum (caudate and putamen). We found that readiness to change correlated
      with different aspects of ventromedial prefrontal gray matter as a function of
      diagnosis. In cocaine users with Cluster C comorbidities, readiness to change
      positively correlated with gyrus rectus gray matter, whereas in cocaine users
      without comorbidities it negatively correlated with rostral anterior cingulate
      cortex gray matter. Moreover, maintenance scores positively correlated with
      dorsomedial prefrontal gray matter in cocaine users with Cluster C comorbidities,
      but negatively correlated with this region in cocaine users with Cluster B and
      cocaine users without comorbidities. Maintenance scores also negatively
      correlated with dorsal striatum gray matter in cocaine users with Cluster C
      comorbidities. We conclude that the link between prefrontal-striatal gray matter
      and treatment motivation is modulated by co-existence of personality disorders. 

PMID- 24904438
TI  - Corrigendum: frontal hemodynamic responses to high frequency yoga breathing in
      schizophrenia: a functional near-infrared spectroscopy study.

PMID- 24904434
TI  - The role of dopamine in schizophrenia from a neurobiological and evolutionary
      perspective: old fashioned, but still in vogue.
AB  - Dopamine is an inhibitory neurotransmitter involved in the pathology of
      schizophrenia. The revised dopamine hypothesis states that dopamine abnormalities
      in the mesolimbic and prefrontal brain regions exist in schizophrenia. However,
      recent research has indicated that glutamate, GABA, acetylcholine, and serotonin
      alterations are also involved in the pathology of schizophrenia. This review
      provides an in-depth analysis of dopamine in animal models of schizophrenia and
      also focuses on dopamine and cognition. Furthermore, this review provides not
      only an overview of dopamine receptors and the antipsychotic effects of
      treatments targeting them but also an outline of dopamine and its interaction
      with other neurochemical models of schizophrenia. The roles of dopamine in the
      evolution of the human brain and human mental abilities, which are affected in
      schizophrenia patients, are also discussed. 

PMID- 24904439
TI  - Impulsive and reflective processes related to alcohol use in young adolescents.
AB  - BACKGROUND: Dual process models suggest that the development of addictive
      behaviors is the result of interplay between impulsive and reflective processes,
      modulated by boundary conditions such as individual or situational factors.
      Empirical support for this model has been repeatedly demonstrated in adult
      samples [for a meta-analysis, see Ref. (1)]. The purpose of this study was to
      test these processes as they relate to emerging alcohol use in adolescents.
      Specifically, the interactive effects of several measures of impulsive and
      reflective processes and working memory capacity (WMC) are examined as predictors
      of changes in alcohol use among adolescents. It was expected that measures of
      reflective processes would better predict changes in alcohol use than measures of
      impulsive processes. Moreover, it was anticipated that WMC would moderate the
      relation between alcohol-specific impulsive and reflective processes and changes
      in adolescent alcohol use. METHODS: The sample consisted of 427 adolescents
      (47.7% male) between 12 and 16 years of age (M = 13.96, SD = 0.78) who reported
      drinking alcohol at least once. Four measures of impulsive processes were
      included. Attentional bias for alcohol was assessed with a Visual Probe Test;
      approach bias toward alcohol was assessed with a Stimulus Response Compatibility
      (SRC) Test; and memory associations with alcohol were assessed with an Implicit
      Association Test (IAT) and a Word Association Test. Two measures of reflective
      measures were included: positive and negative expectancies. WMC was measured
      using a Self-Ordered Pointing Task. RESULTS: RESULTS showed that positive
      expectancies predicted changes in alcohol use, but this effect was qualified by
      an interaction with IAT scores. Moreover, SRC scores predicted changes in alcohol
      use only when negative expectancies were low. Attentional bias and word
      association scores did not predict changes in alcohol use. The relations between
      alcohol-specific processes or reflective processes and alcohol use were not
      moderated by WMC. CONCLUSION: Although there is empirical evidence for the
      validity of the model in predicting heavier alcohol use in adolescents, or
      alcohol abuse and dependence in adults, these observations do not generalize to a
      sample of normative, early adolescents. More specifically, results indicated that
      reflective processes are more important predictors of changes in alcohol use than
      impulsive process during adolescence.

PMID- 24904440
TI  - Water for thought: is there a role for aquaporin channels in delirium?

PMID- 24904441
TI  - Memory, emotion, and age: the work of kinugawa et Al. (2013).

PMID- 24904442
TI  - A Case of Chronic Wernicke's Encephalopathy: A Neuropsychological Study.
AB  - A 54-year-old woman was referred to our Korsakoff Center because of extensive
      cognitive problems following acute Wernicke's encephalopathy (WE). She had a
      relatively short history of alcohol abuse and was found lying on the floor in her
      home by her son. After 5 days without treatment, she was diagnosed with WE in a
      general hospital. During the course of the disease, minimal change to the acute
      situation occurred, with chronic confusion, attention deficits, and incoherent
      behavior symptoms most notable unlike classical Korsakoff's syndrome.
      Neuropsychological assessment after 4 and 16 months after admission to the
      hospital revealed global cognitive decline, with striking impairments in
      attentional, executive, and memory functions. The present case study suggests
      that the state of confusion and the neuropsychological symptoms in WE can become
      chronic in case of very late treatment. We therefore recommend that confused
      alcoholics should receive appropriate parenteral thiamine according to the
      current clinical standards. 

PMID- 24904443
TI  - Can Antipsychotic Agents be Considered as Real Antimanic Treatments?

PMID- 24904445
TI  - Group membership prediction when known groups consist of unknown subgroups: a
      Monte Carlo comparison of methods.
AB  - Classification using standard statistical methods such as linear discriminant
      analysis (LDA) or logistic regression (LR) presume knowledge of group membership
      prior to the development of an algorithm for prediction. However, in many real
      world applications members of the same nominal group, might in fact come from
      different subpopulations on the underlying construct. For example, individuals
      diagnosed with depression will not all have the same levels of this disorder,
      though for the purposes of LDA or LR they will be treated in the same manner. The
      goal of this simulation study was to examine the performance of several methods
      for group classification in the case where within group membership was not
      homogeneous. For example, suppose there are 3 known groups but within each group
      two unknown classes. Several approaches were compared, including LDA, LR,
      classification and regression trees (CART), generalized additive models (GAM),
      and mixture discriminant analysis (MIXDA). Results of the study indicated that
      CART and mixture discriminant analysis were the most effective tools for
      situations in which known groups were not homogeneous, whereas LDA, LR, and GAM
      had the highest rates of misclassification. Implications of these results for
      theory and practice are discussed. 

PMID- 24904444
TI  - What makes deeply encoded items memorable? Insights into the levels of processing
      framework from neuroimaging and neuromodulation.
AB  - When we form new memories, their mnestic fate largely depends upon the cognitive
      operations set in train during encoding. A typical observation in experimental as
      well as everyday life settings is that if we learn an item using semantic or
      "deep" operations, such as attending to its meaning, memory will be better than
      if we learn the same item using more "shallow" operations, such as attending to
      its structural features. In the psychological literature, this phenomenon has
      been conceptualized within the "levels of processing" framework and has been
      consistently replicated since its original proposal by Craik and Lockhart in
      1972. However, the exact mechanisms underlying the memory advantage for deeply
      encoded items are not yet entirely understood. A cognitive neuroscience
      perspective can add to this field by clarifying the nature of the processes
      involved in effective deep and shallow encoding and how they are instantiated in
      the brain, but so far there has been little work to systematically integrate
      findings from the literature. This work aims to fill this gap by reviewing,
      first, some of the key neuroimaging findings on the neural correlates of deep and
      shallow episodic encoding and second, emerging evidence from studies using
      neuromodulatory approaches such as psychopharmacology and non-invasive brain
      stimulation. Taken together, these studies help further our understanding of
      levels of processing. In addition, by showing that deep encoding can be modulated
      by acting upon specific brain regions or systems, the reviewed studies pave the
      way for selective enhancements of episodic encoding processes. 

PMID- 24904437
TI  - Gone to Pot - A Review of the Association between Cannabis and Psychosis.
AB  - Cannabis is the most commonly used illicit drug worldwide, with ~5 million daily
      users worldwide. Emerging evidence supports a number of associations between
      cannabis and psychosis/psychotic disorders, including schizophrenia. These
      associations-based on case-studies, surveys, epidemiological studies, and
      experimental studies indicate that cannabinoids can produce acute, transient
      effects; acute, persistent effects; and delayed, persistent effects that
      recapitulate the psychopathology and psychophysiology seen in schizophrenia.
      Acute exposure to both cannabis and synthetic cannabinoids (Spice/K2) can produce
      a full range of transient psychotomimetic symptoms, cognitive deficits, and
      psychophysiological abnormalities that bear a striking resemblance to symptoms of
      schizophrenia. In individuals with an established psychotic disorder,
      cannabinoids can exacerbate symptoms, trigger relapse, and have negative
      consequences on the course of the illness. Several factors appear to moderate
      these associations, including family history, genetic factors, history of
      childhood abuse, and the age at onset of cannabis use. Exposure to cannabinoids
      in adolescence confers a higher risk for psychosis outcomes in later life and the
      risk is dose-related. Individuals with polymorphisms of COMT and AKT1 genes may
      be at increased risk for psychotic disorders in association with cannabinoids, as
      are individuals with a family history of psychotic disorders or a history of
      childhood trauma. The relationship between cannabis and schizophrenia fulfills
      many but not all of the standard criteria for causality, including temporality,
      biological gradient, biological plausibility, experimental evidence, consistency,
      and coherence. At the present time, the evidence indicates that cannabis may be a
      component cause in the emergence of psychosis, and this warrants serious
      consideration from the point of view of public health policy. 

PMID- 24904446
TI  - Prevention of depression and anxiety symptoms in adolescents: 42 and 54 months
      follow-up of the Aussie Optimism Program-Positive Thinking Skills.
AB  - Anxiety and depression are the most commonly reported mental health problems
      amongst Australian children and adolescents. The Aussie Optimism: Program
      Positive Thinking Skills (AOP-PTS) is a universal intervention program based on
      cognitive and behavioral strategies and aimed to prevent anxiety and depression
      in the middle primary school children aged 9-10 years old. 370 students randomly
      assigned to the intervention and control condition participated in the 42 and 54
      months follow-up study. The intervention group received the AOP-PTS 10-week
      program and the control group received the regular health education curriculum.
      Students were assessed on anxiety, depression and attribution style at school
      whilst parents reported on their child's externalizing and internalizing problems
      at home. Results showed there were no significant reductions across groups in the
      depressive and anxiety symptoms, and attribution style at either 42 or 54 months
      follow-up. These findings suggest that AOP-PTS has short and medium term effects
      but were not sustained in longer term period. Future strategies to achieve the
      desirable outcomes in a longitudinal study are discussed. 

PMID- 24904447
TI  - Color associations for days and letters across different languages.
AB  - While colors are commonplace in everyday metaphors, relatively little is known
      about implicit color associations to linguistic or semantic concepts in a general
      population. In this study, we test color associations for ordered linguistic
      concepts (letters and days). The culture and language specificity of these
      effects was examined in a large group (457) of Dutch-speaking participants, 92
      English-speaking participants, and 49 Hindi-speaking participants. Non-random
      distributions of color choices were revealed; consistencies were found across the
      three language groups in color preferences for both days and letters.
      Interestingly, while the Hindi-speaking participants were presented with letter
      stimuli matched on phonology, their pattern of letter-to-color preferences still
      showed similarities with Dutch- and English-speaking participants. Furthermore,
      we found that that the color preferences corresponded between participants
      indicating to have conscious color experiences with letters or days (putative
      synesthetes) and participants who do not (non-synesthetes). We also explored
      possible mechanisms underlying the color preferences. There were a few specific
      associations, including red for "A," red for "Monday," and white for "Sunday." We
      also explored more general mechanisms, such as overall color preferences as shown
      by Simner et al. (2005). While certainly not all variation can be explained or
      predicted, the results show that regularities are present in color-to-letter or
      color-to-day preferences in both putative synesthetes and non-synesthetes across
      languages. Both letter-to-color and day-to-color preferences were influenced by
      multiple factors. The findings support a notion of abstract concepts (such as
      days and letters) that are not represented in isolation, but are connected to
      perceptual representational systems. Interestingly, at least some of these
      connections to color representations are shared across different
      language/cultural groups. 

PMID- 24904448
TI  - The impact of multisensory integration deficits on speech perception in children
      with autism spectrum disorders.

PMID- 24904449
TI  - Multimodal integration in statistical learning: evidence from the McGurk
      illusion.
AB  - Recent advances in the field of statistical learning have established that
      learners are able to track regularities of multimodal stimuli, yet it is unknown
      whether the statistical computations are performed on integrated representations
      or on separate, unimodal representations. In the present study, we investigated
      the ability of adults to integrate audio and visual input during statistical
      learning. We presented learners with a speech stream synchronized with a video of
      a speaker's face. In the critical condition, the visual (e.g., /gi/) and auditory
      (e.g., /mi/) signals were occasionally incongruent, which we predicted would
      produce the McGurk illusion, resulting in the perception of an audiovisual
      syllable (e.g., /ni/). In this way, we used the McGurk illusion to manipulate the
      underlying statistical structure of the speech streams, such that perception of
      these illusory syllables facilitated participants' ability to segment the speech
      stream. Our results therefore demonstrate that participants can integrate audio
      and visual input to perceive the McGurk illusion during statistical learning. We
      interpret our findings as support for modality-interactive accounts of
      statistical learning. 

PMID- 24904450
TI  - Eye movements during listening reveal spontaneous grammatical processing.
AB  - Recent research using eye-tracking typically relies on constrained visual
      contexts in particular goal-oriented contexts, viewing a small array of objects
      on a computer screen and performing some overt decision or identification.
      Eyetracking paradigms that use pictures as a measure of word or sentence
      comprehension are sometimes touted as ecologically invalid because pictures and
      explicit tasks are not always present during language comprehension. This study
      compared the comprehension of sentences with two different grammatical forms: the
      past progressive (e.g., was walking), which emphasizes the ongoing nature of
      actions, and the simple past (e.g., walked), which emphasizes the end-state of an
      action. The results showed that the distribution and timing of eye movements
      mirrors the underlying conceptual structure of this linguistic difference in the
      absence of any visual stimuli or task constraint: Fixations were shorter and
      saccades were more dispersed across the screen, as if thinking about more dynamic
      events when listening to the past progressive stories. Thus, eye movement data
      suggest that visual inputs or an explicit task are unnecessary to solicit analog
      representations of features such as movement, that could be a key perceptual
      component to grammatical comprehension. 

PMID- 24904451
TI  - How is the McGurk effect modulated by Cued Speech in deaf and hearing adults?
AB  - Speech perception for both hearing and deaf people involves an integrative
      process between auditory and lip-reading information. In order to disambiguate
      information from lips, manual cues from Cued Speech may be added. Cued Speech
      (CS) is a system of manual aids developed to help deaf people to clearly and
      completely understand speech visually (Cornett, 1967). Within this system, both
      labial and manual information, as lone input sources, remain ambiguous.
      Perceivers, therefore, have to combine both types of information in order to get
      one coherent percept. In this study, we examined how audio-visual (AV)
      integration is affected by the presence of manual cues and on which form of
      information (auditory, labial or manual) the CS receptors primarily rely. To
      address this issue, we designed a unique experiment that implemented the use of
      AV McGurk stimuli (audio /pa/ and lip-reading /ka/) which were produced with or
      without manual cues. The manual cue was congruent with either auditory
      information, lip information or the expected fusion. Participants were asked to
      repeat the perceived syllable aloud. Their responses were then classified into
      four categories: audio (when the response was /pa/), lip-reading (when the
      response was /ka/), fusion (when the response was /ta/) and other (when the
      response was something other than /pa/, /ka/ or /ta/). Data were collected from
      hearing impaired individuals who were experts in CS (all of which had either
      cochlear implants or binaural hearing aids; N = 8), hearing-individuals who were
      experts in CS (N = 14) and hearing-individuals who were completely naive of CS (N
      = 15). Results confirmed that, like hearing-people, deaf people can merge
      auditory and lip-reading information into a single unified percept. Without
      manual cues, McGurk stimuli induced the same percentage of fusion responses in
      both groups. Results also suggest that manual cues can modify the AV integration
      and that their impact differs between hearing and deaf people. 

PMID- 24904452
TI  - A Bayesian generative model for learning semantic hierarchies.
AB  - Building fine-grained visual recognition systems that are capable of recognizing
      tens of thousands of categories, has received much attention in recent years. The
      well known semantic hierarchical structure of categories and concepts, has been
      shown to provide a key prior which allows for optimal predictions. The
      hierarchical organization of various domains and concepts has been subject to
      extensive research, and led to the development of the WordNet domains hierarchy
      (Fellbaum, 1998), which was also used to organize the images in the ImageNet
      (Deng et al., 2009) dataset, in which the category count approaches the human
      capacity. Still, for the human visual system, the form of the hierarchy must be
      discovered with minimal use of supervision or innate knowledge. In this work, we
      propose a new Bayesian generative model for learning such domain hierarchies,
      based on semantic input. Our model is motivated by the super-subordinate
      organization of domain labels and concepts that characterizes WordNet, and
      accounts for several important challenges: maintaining context information when
      progressing deeper into the hierarchy, learning a coherent semantic concept for
      each node, and modeling uncertainty in the perception process. 

PMID- 24904453
TI  - How getting noticed helps getting on: successful attention capture doubles
      children's cooperative play.
AB  - Cooperative social interaction is a complex skill that involves maintaining
      shared attention and continually negotiating a common frame of reference.
      Privileged in human evolution, cooperation provides support for the development
      of social-cognitive skills. We hypothesize that providing audio support for
      capturing playmates' attention will increase cooperative play in groups of young
      children. Attention capture was manipulated via an audio-augmented toy to boost
      children's attention bids. Study 1 (48 6- to 11-year-olds) showed that the
      augmented toy yielded significantly more cooperative play in triads compared to
      the same toy without augmentation. In Study 2 (33 7- to 9-year-olds) the
      augmented toy supported greater success of attention bids, which were associated
      with longer cooperative play, associated in turn with better group narratives.
      The results show how cooperation requires moment-by-moment coordination of
      attention and how we can manipulate environments to reveal and support mechanisms
      of social interaction. Our findings have implications for understanding the role
      of joint attention in the development of cooperative action and shared
      understanding. 

PMID- 24904454
TI  - Atypical audio-visual speech perception and McGurk effects in children with
      specific language impairment.
AB  - Audiovisual speech perception of children with specific language impairment (SLI)
      and children with typical language development (TLD) was compared in two
      experiments using /aCa/ syllables presented in the context of a masking release
      paradigm. Children had to repeat syllables presented in auditory alone, visual
      alone (speechreading), audiovisual congruent and incongruent (McGurk) conditions.
      Stimuli were masked by either stationary (ST) or amplitude modulated (AM) noise.
      Although children with SLI were less accurate in auditory and audiovisual speech
      perception, they showed similar auditory masking release effect than children
      with TLD. Children with SLI also had less correct responses in speechreading than
      children with TLD, indicating impairment in phonemic processing of visual speech
      information. In response to McGurk stimuli, children with TLD showed more fusions
      in AM noise than in ST noise, a consequence of the auditory masking release
      effect and of the influence of visual information. Children with SLI did not show
      this effect systematically, suggesting they were less influenced by visual
      speech. However, when the visual cues were easily identified, the profile of
      responses to McGurk stimuli was similar in both groups, suggesting that children
      with SLI do not suffer from an impairment of audiovisual integration. An analysis
      of percent of information transmitted revealed a deficit in the children with
      SLI, particularly for the place of articulation feature. Taken together, the data
      support the hypothesis of an intact peripheral processing of auditory speech
      information, coupled with a supra modal deficit of phonemic categorization in
      children with SLI. Clinical implications are discussed. 

PMID- 24904456
TI  - Implication of the anterior commissure in the allocation of attention to action.
AB  - Our recent target article on the allocation of attention to action (herein called
      the AAA model; Franz, 2012) considered implicated subcortical processes and
      networks in people with intact corpus callosum (CC) and people without a CC due
      to commissurotomy or callosotomy. However, a small error in print-namely that the
      term "commissurotomy" was printed in place of "callosotomy" in some instances-led
      us to further explore whether any key functional roles have been attributed to
      the two primary cortical commissures (the anterior and posterior commissures)
      which remain intact in people with callosotomy, and if so, whether those would be
      relevant to our current AAA framework. Although existing evidence is sparse, here
      we consider the hypothesis that the anterior commissure (AC) is a remnant fiber
      tract which has been largely replaced with evolution of the CC (and we do not
      herein discuss the posterior commissure further). Indeed, a dearth of studies is
      available on the AC, calling the need for further research. Herein, we briefly
      review literature on the AC in humans and then propose a method that might be
      worthwhile to pursue in future studies. 

PMID- 24904457
TI  - Sound mind, irrational behavior?

PMID- 24904458
TI  - The intentionality of smell.
AB  - If any sense modality represents, vision does, but argument is needed to show
      that smell does. This paper rebuts two reasons for doubting that smell
      represents, and offers several arguments that it does. The paper then considers
      several recent proposals as to exactly what a smell represents, and defends a
      version of the author's original proposal-that a smell represents a miasma in the
      air-against its competitors. 

PMID- 24904459
TI  - The subjective meaning of cognitive architecture: a Marrian analysis.
AB  - Marr famously decomposed cognitive theories into three levels. Newell, Pylyshyn,
      and Anderson offered parallel decompositions of cognitive architectures, which
      are psychologically plausible computational formalisms for expressing
      computational models of cognition. These analyses focused on the objective
      meaning of each level - how it supports computational models that correspond to
      cognitive phenomena. This paper develops a complementary analysis of the
      subjective meaning of each level - how it helps cognitive scientists understand
      cognition. It then argues against calls to eliminatively reduce higher levels to
      lower levels, for example, in the name of parsimony. Finally, it argues that the
      failure to attend to the multiple meanings and levels of cognitive architecture
      contributes to the current, disunified state of theoretical cognitive science. 

PMID- 24904455
TI  - Internally directed cognition and mindfulness: an integrative perspective derived
      from predictive and reactive control systems theory.
AB  - In the present paper, we will apply the predictive and reactive control systems
      (PARCS) theory as a framework that integrates competing theories of neural
      substrates of awareness by describing the "default mode network" (DMN) and
      anterior insula (AI) as parts of two different behavioral and homeostatic control
      systems. The DMN, a network that becomes active at rest when there is no external
      stimulation or task to perform, has been implicated in self-reflective awareness
      and prospection. By contrast, the AI is associated with awareness and task
      related attention. This has led to competing theories stressing the role of the
      DMN in self-awareness vs. the role of interoceptive and emotional information
      integration in the AI in awareness of the emotional moment. In PARCS, the
      respective functions of the DMN and AI in a specific control system explains
      their association with different qualities of awareness, and how mental states
      can shift from one state (e.g., prospective self-reflection) to the other (e.g.,
      awareness of the emotional moment) depending on the relative dominance of control
      systems. These shifts between reactive and predictive control are part of
      processes that enable the intake of novel information, integration of this novel
      information within existing knowledge structures, and the creation of a
      continuous personal context in which novel information can be integrated and
      understood. As such, PARCS can explain key characteristics of mental states, such
      as their temporal and spatial focus (e.g., a focus on the here and now vs. the
      future; a first person vs. a third person perspective). PARCS further relates
      mental states to brain states and functions, such as activation of the DMN or
      hemispheric asymmetry in frontal cortical functions. Together, PARCS deepens the
      understanding of a broad range of mental states, including mindfulness, mind
      wandering, rumination, autobiographical memory, imagery, and the experience of
      self. 

PMID- 24904460
TI  - Prediction-learning in infants as a mechanism for gaze control during object
      exploration.
AB  - We are pursuing the hypothesis that visual exploration and learning in young
      infants is achieved by producing gaze-sample sequences that are sequentially
      predictable. Our recent analysis of infants' gaze patterns during image free
      viewing (Schlesinger and Amso, 2013) provides support for this idea. In
      particular, this work demonstrates that infants' gaze samples are more easily
      learnable than those produced by adults, as well as those produced by three
      artificial-observer models. In the current study, we extend these findings to a
      well-studied object-perception task, by investigating 3-month-olds' gaze patterns
      as they view a moving, partially occluded object. We first use infants' gaze data
      from this task to produce a set of corresponding center-of-gaze (COG) sequences.
      Next, we generate two simulated sets of COG samples, from image-saliency and
      random-gaze models, respectively. Finally, we generate learnability estimates for
      the three sets of COG samples by presenting each as a training set to an SRN.
      There are two key findings. First, as predicted, infants' COG samples from the
      occluded-object task are learned by a pool of simple recurrent networks faster
      than the samples produced by the yoked, artificial-observer models. Second, we
      also find that resetting activity in the recurrent layer increases the network's
      prediction errors, which further implicates the presence of temporal structure in
      infants' COG sequences. We conclude by relating our findings to the role of image
      saliency and prediction-learning during the development of object perception. 

PMID- 24904461
TI  - Registered report: measuring unconscious deception detection by skin temperature.
AB  - Findings from the deception detection literature suggest that although people are
      not skilled in consciously detecting a liar, they may intuit that something about
      the person telling a lie is off. In the current proposal, we argue that observing
      a liar influences the observer's physiology even though the observer may not be
      consciously aware of being lied to (i.e., the observers' direct deception
      judgment does not accurately differentiate between liars and truth-tellers). To
      test this hypothesis, participants' finger temperature will be measured while
      they watch videos of persons who are either honest or dishonest about their
      identity. We hypothesize that skin temperature will be lower when observing a
      liar than when observing a truth-teller. Additionally, we test whether perceiving
      a liar influences finger skin temperature differently when an individual is, or
      is not, alerted to the possibility of deceit. We do this by varying participants'
      awareness of the fact that they might be lied to. Next to measuring physiological
      responses to liars and truth-tellers, self-reported direct and indirect veracity
      judgments (i.e., trustworthiness and liking) of the target persons will be
      assessed. We hypothesize that indirect veracity judgments will better distinguish
      between liars and truth-tellers than direct veracity judgments. 

PMID- 24904463
TI  - Effortless inhibition: habit mediates the relation between self-control and
      unhealthy snack consumption.
AB  - In contrast to prevailing beliefs, recent research suggests that trait self
      control promotes health behavior not because those high in self-control are more
      successful at resisting single temptations, but rather because they develop
      adaptive habits. The present paper presents a first empirical test of this novel
      suggestion by investigating the mediating role of habit in explaining the
      relation between self-control and unhealthy snacking behavior. Results showed
      that self-control was negatively associated with unhealthy snack consumption and
      unhealthy snacking habits. As hypothesized, the relation between self-control and
      unhealthy snack intake was mediated by habit strength. Self-control was not
      associated with fruit consumption or fruit consumption habits. These results
      provide the first evidence for the notion that high self-control may influence
      the formation of habits and in turn affect behavior. Moreover, results imply that
      self-control may be particularly influential in case of inhibiting unhealthy food
      intake rather than promoting healthy food intake. 

PMID- 24904462
TI  - Longitudinal and concurrent links between memory span, anxiety symptoms, and
      subsequent executive functioning in young children.
AB  - It has been conjectured that basic individual differences in attentional control
      influence higher-level executive functioning and subsequent academic performance
      in children. The current study sets out to complement the limited body of
      research on early precursors of executive functions (EFs). It provides both a
      cross-sectional, as well as a longitudinal exploration of the relationship
      between EF and more basic attentional control mechanisms, assessed via children's
      performance on memory storage tasks, and influenced by individual differences in
      anxiety. Multiple measures of verbal and visuospatial short-term memory (STM)
      were administered to children between 3 and 6 years old, alongside a non-verbal
      measure of intelligence, and a parental report of anxiety symptoms. After 9
      months, children were re-tested on the same STM measures, at which time we also
      administered multiple measures of executive functioning: verbal and visuospatial
      working memory (WM), inhibition, and shifting. A cross-sectional view of STM
      development indicated that between 3 and 6 years the trajectory of visuospatial
      STM and EF underwent a gradual linear improvement. However, between 5 and 6 years
      progress in verbal STM performance stagnated. Hierarchical regression models
      revealed that trait anxiety was negatively associated with WM and shifting, while
      non-verbal intelligence was positively related to WM span. When age, gender, non
      verbal intelligence, and anxiety were controlled for, STM (measured at the first
      assessment) was a very good predictor of overall executive performance. The
      models were most successful in predicting WM, followed by shifting, yet poorly
      predicted inhibition measures. Further longitudinal research is needed to
      directly address the contribution of attentional control mechanisms to emerging
      executive functioning and to the development of problematic behavior during early
      development. 

PMID- 24904464
TI  - Educational attainment in poor comprehenders.
AB  - To date, only one study has investigated educational attainment in poor (reading)
      comprehenders, providing evidence of poor performance on national UK school tests
      at age 11 years relative to peers (Cain and Oakhill, 2006). In the present study,
      we adopted a longitudinal approach, tracking attainment on such tests from 11
      years to the end of compulsory schooling in the UK (age 16 years). We aimed to
      investigate the proposal that educational weaknesses (defined as poor performance
      on national assessments) might become more pronounced over time, as the
      curriculum places increasing demands on reading comprehension. Participants
      comprised 15 poor comprehenders and 15 controls; groups were matched for
      chronological age, nonverbal reasoning ability and decoding skill. Children were
      identified at age 9 years using standardized measures of nonverbal reasoning,
      decoding and reading comprehension. These measures, along with a measure of oral
      vocabulary knowledge, were repeated at age 11 years. Data on educational
      attainment were collected from all participants (n = 30) at age 11 and from a
      subgroup (n = 21) at 16 years. Compared to controls, educational attainment in
      poor comprehenders was lower at ages 11 and 16 years, an effect that was
      significant at 11 years. When poor comprehenders were compared to national
      performance levels, they showed significantly lower performance at both time
      points. Low educational attainment was not evident for all poor comprehenders.
      Nonetheless, our findings point to a link between reading comprehension
      difficulties in mid to late childhood and poor educational outcomes at ages 11
      and 16 years. At these ages, pupils in the UK are making key transitions: they
      move from primary to secondary schools at 11, and out of compulsory schooling at
      16. 

PMID- 24904465
TI  - ADHD among young adults born at extremely low birth weight: the role of fluid
      intelligence in childhood.
AB  - Poor executive function (EF) has been linked to attention-deficit/hyperactivity
      disorder (ADHD). Children born at extremely low birth weight (ELBW; <1000 g) have
      been found to show both poor EF, as well as elevated levels of symptoms of ADHD.
      In the present study, we examined whether fluid intelligence moderates the link
      between birth weight and later ADHD symptoms by prospectively following a cohort
      of 179 survivors who were born at ELBW. When participants were 8 years-old, they
      were matched with 145 normal birth weight (NBW; >=2500 g) control participants.
      At age 8, fluid intelligence was measured, and during young adulthood (ages 22
      26), participants' self-reported levels of ADHD symptoms were examined. We found
      that ELBW survivors, who also showed poor fluid intelligence, had the highest
      rates of ADHD symptoms, and particularly, symptoms of inattention. These findings
      point to the importance of examining developmental trajectories that contribute
      to risk for psychopathology in those exposed to intrauterine adversity. 

PMID- 24904466
TI  - Executive function and food approach behavior in middle childhood.
AB  - Executive function (EF) has long been considered to be a unitary, domain-general
      cognitive ability. However, recent research suggests differentiating "hot"
      affective and "cool" cognitive aspects of EF. Yet, findings regarding this two
      factor construct are still inconsistent. In particular, the development of this
      factor structure remains unclear and data on school-aged children is lacking.
      Furthermore, studies linking EF and overweight or obesity suggest that EF
      contributes to the regulation of eating behavior. So far, however, the links
      between EF and eating behavior have rarely been investigated in children and non
      clinical populations. First, we examined whether EF can be divided into hot and
      cool factors or whether they actually correspond to a unitary construct in middle
      childhood. Second, we examined how hot and cool EF are associated with different
      eating styles that put children at risk of becoming overweight during
      development. Hot and cool EF were assessed experimentally in a non-clinical
      population of 1657 elementary-school children (aged 6-11 years). The "food
      approach" behavior was rated mainly via parent questionnaires. Findings indicate
      that hot EF is distinguishable from cool EF. However, only cool EF seems to
      represent a coherent functional entity, whereas hot EF does not seem to be a
      homogenous construct. This was true for a younger and an older subgroup of
      children. Furthermore, different EF components were correlated with eating
      styles, such as responsiveness to food, desire to drink, and restrained eating in
      girls but not in boys. This shows that lower levels of EF are not only seen in
      clinical populations of obese patients but are already associated with food
      approach styles in a normal population of elementary school-aged girls. Although
      the direction of effect still has to be clarified, results point to the
      possibility that EF constitutes a risk factor for eating styles contributing to
      the development of overweight in the long-term. 

PMID- 24904467
TI  - Memory impairment is not sufficient for choice blindness to occur.
AB  - Choice blindness refers to the phenomenon that people can be easily misled about
      the choices they made in the recent past. The aim of this study was to explore
      the cognitive mechanisms underlying choice blindness. Specifically, we tested
      whether memory impairment may account for choice blindness. A total of N = 88
      participants provided sympathy ratings on 10-point scales for 20 female faces.
      Subsequently, participants motivated some of their ratings. However, on three
      trials, they were presented with sympathy ratings that deviated from their
      original ratings by three full scale points. On nearly 41% of the trials,
      participants failed to detect (i.e., were blind) the manipulation. After a short
      interval, participants were informed that some trials had been manipulated and
      were asked to recall their original ratings. Participants adopted the manipulated
      outcome in only 3% of the trials. Furthermore, the extent to which the original
      ratings were accurately remembered was not higher for detected as compared with
      non-detected trials. From a theoretical point of view our findings indicate that
      memory impairment does not fully account for blindness phenomena. 

PMID- 24904468
TI  - Counterfactual thinking in moral judgment: an experimental study.
AB  - Counterfactual thinking is thinking about a past that did not happen. This is
      often the case in "if only..." situations, where we wish something had or had not
      happened. To make a choice in a moral decision-making situation is particularly
      hard and, therefore, may be often associated with the imagination of a different
      outcome. The main aim of the present study is to investigate counterfactual
      thinking in the context of moral reasoning. We used a modified version of
      Greene's moral dilemmas test, studying both the time needed to provide a
      counterfactual in the first and third person and the type of given response (in
      context-out of context) in a sample of 90 healthy subjects. We found a longer
      response time for personal vs. impersonal moral dilemmas. This effect was
      enhanced in the first person perspective, while in the elderly there was an
      overall slowing of response time. Out of context/omissive responses were more
      frequent in the case of personal moral dilemmas presented in the first person
      version, with females showing a marked increase in this kind of response. These
      findings suggest that gender and perspective have a critical role in
      counterfactual thinking in the context of moral reasoning, and may have
      implications for the understanding of gender-related inclinations as well as
      differences in moral judgment. 

PMID- 24904470
TI  - The effects of visual half-field priming on the categorization of familiar
      intransitive gestures, tool use pantomimes, and meaningless hand movements.
AB  - Although the control of meaningful gestures is one of the most left-lateralized
      functions, the relative contribution of the two hemispheres to their processing
      is still debated. We tested the effects of primes appearing in the left or right
      visual field in the form of pictures (Experiment 1), and words (Experiment 2) on
      categorization of movies showing intransitive ("communicative") gestures, tool
      use (transitive) pantomimes, and meaningless movements. Fifteen participants
      (eight women) watched 36 movies (12 from each category) primed for 150 ms with
      either a congruent or incongruent stimulus followed by a 50-ms mask. On congruent
      trials, a picture or word was directly related to the presented gesture,
      including nonsense pictures or non-words for meaningless actions. On incongruent
      trials, a picture or word belonged to a different category. In Experiment 1,
      intransitive gestures were categorized significantly faster than the other two
      types of hand movements. Moreover, whereas the categorization of transitive
      gestures was significantly facilitated by congruent pictures on the right, the
      effect was weaker for intransitive, and reversed for meaningless movements. In
      Experiment 2, intransitive gestures were again categorized significantly faster,
      but transitive significantly slower than the other two gesture categories. Yet,
      there was now a significant facilitation of intransitive, and inhibition of
      transitive gesture categorization following congruent prime words in the right
      visual field, and significantly faster categorization of intransitive gestures
      following incongruent words in the left visual field. These outcomes lend support
      to the complexity account of differences in left-hemisphere representations of
      meaningful gestures reported in the neuropsychological, behavioral, and
      neuroimaging literature. Nevertheless, they also indicate that the
      representations of intransitive gestures show some differential, and sometimes
      counterintuitive sensitivity to right hemisphere processing. 

PMID- 24904471
TI  - Can creative productivity be both positively and negatively correlated with
      psychopathology? Yes!

PMID- 24904469
TI  - Neural processing of visual information under interocular suppression: a critical
      review.
AB  - When dissimilar stimuli are presented to the two eyes, only one stimulus
      dominates at a time while the other stimulus is invisible due to interocular
      suppression. When both stimuli are equally potent in competing for awareness,
      perception alternates spontaneously between the two stimuli, a phenomenon called
      binocular rivalry. However, when one stimulus is much stronger, e.g., due to
      higher contrast, the weaker stimulus can be suppressed for prolonged periods of
      time. A technique that has recently become very popular for the investigation of
      unconscious visual processing is continuous flash suppression (CFS): High
      contrast dynamic patterns shown to one eye can render a low-contrast stimulus
      shown to the other eye invisible for up to minutes. Studies using CFS have
      produced new insights but also controversies regarding the types of visual
      information that can be processed unconsciously as well as the neural sites and
      the relevance of such unconscious processing. Here, we review the current state
      of knowledge in regard to neural processing of interocularly suppressed
      information. Focusing on recent neuroimaging findings, we discuss whether and to
      what degree such suppressed visual information is processed at early and more
      advanced levels of the visual processing hierarchy. We review controversial
      findings related to the influence of attention on early visual processing under
      interocular suppression, the putative differential roles of dorsal and ventral
      areas in unconscious object processing, and evidence suggesting privileged
      unconscious processing of emotional and other socially relevant information. On a
      more general note, we discuss methodological and conceptual issues, from
      practical issues of how unawareness of a stimulus is assessed to the overarching
      question of what constitutes an adequate operational definition of unawareness.
      Finally, we propose approaches for future research to resolve current
      controversies in this exciting research area. 

PMID- 24904472
TI  - Distinct mechanisms subserve location- and object-based visual attention.
AB  - Visual attention can be allocated to either a location or an object, named
      location- or object-based attention, respectively. Despite the burgeoning
      evidence in support of the existence of two kinds of attention, little is known
      about their underlying mechanisms in terms of whether they are achieved by
      enhancing signal strength or excluding external noises. We adopted the noise
      masking paradigm in conjunction with the double-rectangle method to probe the
      mechanisms of location-based attention and object-based attention. Two rectangles
      were shown, and one end of one rectangle was cued, followed by the target
      appearing at (a) the cued location; (b) the uncued end of the cued rectangle; and
      (c) the equal-distant end of the uncued rectangle. Observers were required to
      detect the target that was superimposed at different levels of noise contrast. We
      explored how attention affects performance by assessing the threshold versus
      external noise contrast (TvC) functions and fitted them with a divisive
      inhibition model. Results show that location-based attention - lower threshold at
      cued location than at uncued location - was observed at all noise levels, a
      signature of signal enhancement. However, object-based attention - lower
      threshold at the uncued end of the cued than at the uncued rectangle - was found
      only in high-noise conditions, a signature of noise exclusion. Findings here shed
      a new insight into the current theories of object-based attention. 

PMID- 24904473
TI  - The potential adverse effect of energy drinks on executive functions in early
      adolescence.
AB  - INTRODUCTION: Manufacturers of energy drinks (EDs) claim their products improve
      cognitive performance. Young adolescents are in a critical developmental phase.
      The impact of ED intake on their development is not yet clear. Therefore, we
      studied the associations of both caffeine intake and ED consumption with
      executive functions (EFs), and the role of pubertal status and sleeping problems.
      METHODS: A sample of 509 participants (mean age: 13.1 years, SD 0.85; age range:
      11-16 years) participated in the study. The level of pubertal development was
      classified in five pubertal status categories. Participants were asked to report
      their caffeine (for example coffee) and ED consumption for each day of the week.
      In addition, they indicated sleep quality by reporting problems falling asleep or
      waking up and/or interrupted sleep. EFs were assessed by self- and parent reports
      of the Behavior Rating Inventory of Executive Function (BRIEF). RESULTS:
      Consuming on average one or more ED(s) a day was associated with more problems in
      self-reported behavior regulation and metacognition, and with more problems in
      parent-reported metacognition. Only high caffeine consumption (two or more cups a
      day) was associated with parent-reported problems with metacognition. The sum of
      caffeine and ED use was associated with a higher amount of problems with self
      reported metacognition and parent reported behavior regulation. The effect
      estimates for the association between caffeine and ED use combined and EFs did
      not exceed those of EDs or caffeine separately. Adjusting for pubertal status,
      gender, educational level, number of sleeping problems and hours of sleep did not
      change the effect estimates substantially. CONCLUSION: The observed associations
      between ED consumption and EFs suggest that regular consumption of EDs-even in
      moderate amounts-may have a negative impact on daily life behaviors related to EF
      in young adolescents.

PMID- 24904474
TI  - Children's giving: moral reasoning and moral emotions in the development of
      donation behaviors.
AB  - This study investigated the role of moral reasoning and moral emotions (i.e.,
      sympathy and guilt) in the development of young children's donating behavior (N =
      160 4- and 8-year-old children). Donating was measured through children's
      allocation of resources (i.e., stickers) to needy peers and was framed as a
      donation to "World Vision." Children's sympathy was measured with both self- and
      primary caregiver-reports and participants reported their anticipation of guilt
      feelings following actions that violated prosocial moral norms, specifically the
      failure to help or share. Participants also provided justifications for their
      anticipated emotions, which were coded as representing moral or non-moral
      reasoning processes. Children's moral reasoning emerged as a significant
      predictor of donating behavior. In addition, results demonstrated significant
      developmental and gender effects, with 8-year-olds donating significantly more
      than 4-year-olds and 4-year-old girls making higher value donations than boys of
      the same age. We discuss donation behaviors within the broader context of giving
      and highlight the moral developmental antecedents of giving behaviors in
      childhood. 

PMID- 24904475
TI  - Learning mathematics in two dimensions: a review and look ahead at teaching and
      learning early childhood mathematics with children's literature.
AB  - In the past 25 years an identifiable interest in using children's literature in
      mathematics learning emerged (Clyne and Griffiths, 1991; Welchman-Tischler, 1992;
      Hong, 1996; Hellwig etal., 2000; Haury, 2001). We critically review the
      rationales given for the use of picture books in mathematics learning, with a
      special focus on geometry due to its underrepresentation in this body of
      literature and the need for greater focus on this topic. The benefits and
      effectiveness of using picture books for children's mathematics learning and
      interest have been documented (Hong, 1996; O'Neill etal., 2004; Young-Loveridge,
      2004). For geometry, although much learning of shape ideas should be hands-on,
      two-dimensional figures are essential to develop children's understanding of
      plane geometry. Books may effectively engage pre-literate children with plane
      shapes (van den Heuvel-Panhuizen and van den Boogaard, 2008; Skoumpourdi and
      Mpakopoulou, 2011) and shapes as gestalt wholes or prototypes (van Hiele, 1986;
      Clements etal., 1999; Hannibal, 1999). We review several guidelines and
      evaluative criteria for book selection, including Cianciolo (2000), Schiro
      (1997), Hunsader (2004), and van den Heuvel-Panhuizen and Elia (2012). Geometry
      concepts have proven challenging for young students, but their difficulties may
      stem, in part, from inadequate teacher training and professional development
      (Clements and Sarama, 2000; Chard etal., 2008) which lead to misconceptions
      (Oberdorf and Taylor-Cox, 1999; Inan and Dogan-Temur, 2010). Using picture books
      in teacher training may be an inviting way for early childhood teachers to
      enhance their own knowledge. We will examine the literature for guidance on
      incorporating children's literature into teacher training. In closing we will
      outline a comprehensive, multi-pronged agenda for best instructional practices
      for selection and use of children's books in mathematics activities and for
      teacher training. 

PMID- 24904477
TI  - Preliminary evidence that different mechanisms underlie the anger superiority
      effect in children with and without Autism Spectrum Disorders.
AB  - Previous studies have demonstrated that angry faces capture humans' attention
      more rapidly than emotionally positive faces. This phenomenon is referred to as
      the anger superiority effect (ASE). Despite atypical emotional processing, adults
      and children with Autism Spectrum Disorders (ASD) have been reported to show ASE
      as well as typically developed (TD) individuals. So far, however, few studies
      have clarified whether or not the mechanisms underlying ASE are the same for both
      TD and ASD individuals. Here, we tested how TD and ASD children process schematic
      emotional faces during detection by employing a recognition task in combination
      with a face-in-the-crowd task. Results of the face-in-the-crowd task revealed the
      prevalence of ASE both in TD and ASD children. However, the results of the
      recognition task revealed group differences: In TD children, detection of angry
      faces required more configural face processing and disrupted the processing of
      local features. In ASD children, on the other hand, it required more feature
      based processing rather than configural processing. Despite the small sample
      sizes, these findings provide preliminary evidence that children with ASD, in
      contrast to TD children, show quick detection of angry faces by extracting local
      features in faces. 

PMID- 24904476
TI  - Breaking continuous flash suppression: competing for consciousness on the pre
      semantic battlefield.
AB  - Traditionally, interocular suppression is believed to disrupt high-level (i.e.,
      semantic or conceptual) processing of the suppressed visual input. The
      development of a new experimental paradigm, breaking continuous flash suppression
      (b-CFS), has caused a resurgence of studies demonstrating high-level processing
      of visual information in the absence of visual awareness. In this method the time
      it takes for interocularly suppressed stimuli to breach the threshold of
      visibility, is regarded as a measure of access to awareness. The aim of the
      current review is twofold. First, we provide an overview of the literature using
      this b-CFS method, while making a distinction between two types of studies: those
      in which suppression durations are compared between different stimulus classes
      (such as upright faces versus inverted faces), and those in which suppression
      durations are compared for stimuli that either match or mismatch concurrently
      available information (such as a colored target that either matches or mismatches
      a color retained in working memory). Second, we aim at dissociating high-level
      processing from low-level (i.e., crude visual) processing of the suppressed
      stimuli. For this purpose, we include a thorough review of the control conditions
      that are used in these experiments. Additionally, we provide recommendations for
      proper control conditions that we deem crucial for disentangling high-level from
      low-level effects. Based on this review, we argue that crude visual processing
      suffices for explaining differences in breakthrough times reported using b-CFS.
      As such, we conclude that there is as yet no reason to assume that interocularly
      suppressed stimuli receive full semantic analysis. 

PMID- 24904478
TI  - The association between higher education and approximate number system acuity.
AB  - Humans are equipped with an approximate number system (ANS) supporting non
      symbolic numerosity representation. Studies indicate a relationship between ANS
      precision (acuity) and math achievement. Whether the ANS is a prerequisite for
      learning mathematics or if mathematics education enhances the ANS remains an open
      question. We investigated the association between higher education and ANS acuity
      with university students majoring in subjects with varying amounts of mathematics
      (mathematics, business, and humanities), measured either early (First year) or
      late (Third year) in their studies. The results suggested a non-significant trend
      where students taking more mathematics had better ANS acuity and a significant
      improvement in ANS acuity as a function of study length that was mainly confined
      to the business students. The results provide partial support for the hypothesis
      that education in mathematics can enhance the ANS acuity. 

PMID- 24904479
TI  - Conflict components of the Stroop effect and their "control".

PMID- 24904480
TI  - Box-and-arrow explanations need not be more abstract than neuroscientific
      mechanism descriptions.
AB  - The nature of the relationship between box-and-arrow (BA) explanations and
      neuroscientific mechanism descriptions (NMDs) is a key foundational issue for
      cognitive science. In this article we attempt to identify the nature of the
      constraints imposed by BA explanations on the formulation of NMDs. On the basis
      of a case study about motor control, we argue that BA explanations and NMDs both
      identify regularities that hold in the system, and that these regularities place
      constraints on the formulation of NMDs from BA analyses, and vice versa. The
      regularities identified in the two kinds of explanation play a crucial role in
      reasoning about the relationship between them, and in justifying the use of
      neuroscientific experimental techniques for the empirical testing of BA analyses
      of behavior. In addition, we make claims concerning the similarities and
      differences between BA analyses and NMDs. First, we argue that both types of
      explanation describe mechanisms. Second, we propose that they differ in terms of
      the theoretical vocabulary used to denote the entities and properties involved in
      the mechanism and engaging in regular, mutual interactions. On the contrary, the
      notion of abstractness, defined as omission of detail, does not help to
      distinguish BA analyses from NMDs: there is a sense in which BA analyses are more
      detailed than NMDs. In relation to this, we also focus on the nature of the extra
      detail included in NMDs and missing from BA analyses, arguing that such detail
      does not always concern how the system works. Finally, we propose reasons for
      doubting that BA analyses, unlike NMDs, may be considered "mechanism sketches."
      We have developed these views by critically analyzing recent claims in the
      philosophical literature regarding the foundations of cognitive science. 

PMID- 24904481
TI  - The effect of attentional load on implicit sequence learning in children and
      young adults.
AB  - We investigated the effect of a secondary task on implicit sequence learning in
      children and young adults. A serial reaction time (SRT) task was administered to
      8-to-10 year old children and 18-to-22 year old adults. Participants reacted to
      the location of a target presented in one of four locations on the screen with a
      spatially corresponding response key. Unknown to participants, the location at
      which the target appeared was structured according to a deterministic sequence.
      Occasionally, the black target dot was replaced by a red target dog. To assess
      the effect of attentional load on implicit sequence learning, half of the
      participants of each age group was assigned to the single task condition, while
      the other half executed the task under dual task conditions. Whereas participants
      in the single task condition could ignore the change in target identity, dual
      task participants additionally had to count the number of times the black dot was
      replaced by a red dog to increase the attentional load. Sequence learning was
      tested under single task conditions in both conditions. Z-transformed results
      indicate that young adults generally showed more sequence learning than children.
      Importantly, the secondary task had no effect on sequence learning in children,
      since children learned as much under dual task conditions as under single task
      conditions. Adults, on the other hand, showed a different result pattern, as they
      displayed more sequence learning under single task than under dual task
      conditions. We surmise that this result is due to the vainly attempt of adults,
      but not children, to integrate both sequences. 

PMID- 24904482
TI  - Individual differences in associative learning.

PMID- 24904483
TI  - The control processes and subjective well-being of Chinese teachers: evidence of
      convergence with and divergence from the key propositions of the motivational
      theory of life-span development.
AB  - An analytical review of the motivational theory of life-span development reveals
      that this theory has undergone a series of elegant theoretical integrations. Its
      claim to universality nonetheless brings forth unresolved controversies. With the
      purpose of scrutinizing the key propositions of this theory, an empirical study
      was designed to examine the control processes and subjective well-being of
      Chinese teachers (N = 637). The OPS-Scales (Optimization in Primary and Secondary
      Control Scales) for the Domain of Teaching were constructed to assess patterns of
      control processes. Three facets of subjective well-being were investigated with
      the Positive and Negative Affect Schedule, the Life Satisfaction Scale, and the
      Subjective Vitality Scale. The results revealed certain aspects of alignment with
      and certain divergences from the key propositions of the motivational theory of
      life-span development. Neither "primacy of primary control" nor "primacy of
      secondary control" was clearly supported. Notably, using different criteria for
      subjective well-being yielded different subtypes of primary and secondary control
      as predictors. The hypothesized life-span trajectories of primary and secondary
      control received limited support. To advance the theory in this area, we
      recommend incorporating Lakatos' ideas about sophisticated falsification by
      specifying the hard core of the motivational theory of life-span development and
      articulating new auxiliary hypotheses. 

PMID- 24904484
TI  - The development of sympathy from 5 to 7 years: increase, decline or stability? A
      longitudinal study.
AB  - In the present study the development of sympathy in a group of 85 children (43
      girls) was investigated over a 3-year period, starting with the last year of
      child care, when the children were 5 years-old. Sympathy was measured via
      different measures: two standardized observations, where the children were
      observed as they witnessed the distress of a puppet in two different situations;
      two follow-up interviews with the children immediately after the observations; a
      self-report questionnaire and two other-report questionnaires by parents and
      teachers. At all three periods the observations and the children's self-reports
      (interviews, questionnaire) were intercorrelated. The teachers' and the parents'
      reports were not significantly correlated with any of the other measures at time
      1. At times 2 and 3, a few low but significant correlations emerged. As a
      consequence, the other reports were dropped from further analyses and a composed
      sympathy measure consisting of observations and self-reports was created. Rank
      order stability of this composed measure over the course of the 3 years proved to
      be high; suggesting that interindividual differences maintained stability. Mean
      level differences showed a significant increase over the course of the study with
      the highest increase in the initial 2 years. Neither gender nor the interaction
      between gender and time were significant. In conclusion, the measurement of
      sympathy has proven valid for the childrens' observations and self-reports. To
      the question of age-correlated development, stability in sympathy is firstly high
      and secondly sympathy increases mainly during the time between the last year in
      child care and the first year in elementary school. 

PMID- 24904485
TI  - Designing a "better" brain: insights from experts and savants.

PMID- 24904486
TI  - The mind-body relationship in psychotherapy: grounded cognition as an explanatory
      framework.
AB  - As a discipline, psychology is defined by its location in the ambiguous space
      between mind and body, but theories underpinning the application of psychology in
      psychotherapy are largely silent on this fundamental metaphysical issue. This is
      a remarkable state of affairs, given that psychotherapy is typically a real-time
      meeting between two embodied agents, with the goal of facilitating behavior
      change in one party. The overarching aim of this paper is to problematize the
      mind-body relationship in psychotherapy in the service of encouraging advances in
      theory and practice. The paper briefly explores various psychotherapeutic
      approaches to help explicate relationships between mind and body from these
      perspectives. Themes arising from this analysis include a tendency toward dualism
      (separation of mind and body from the conceptualization of human functioning),
      exclusivism (elimination of either mind or body from the conceptualization of
      human functioning), or mind-body monism (conceptualization of mind and body as a
      single, holistic system). We conclude that the literature, as a whole, does not
      demonstrate consensus, regarding the relationship between mind and body in
      psychotherapy. We then introduce a contemporary, holistic, psychological
      conceptualization of the relationship between mind and body, and argue for its
      potential utility as an organizing framework for psychotherapeutic theory and
      practice. The holistic approach we explore, "grounded cognition," arises from a
      long philosophical tradition, is influential in current cognitive science, and
      presents a coherent empirically testable framework integrating subjective and
      objective perspectives. Finally, we demonstrate how this "grounded cognition"
      perspective might lead to advances in the theory and practice of psychotherapy. 

PMID- 24904487
TI  - Tool use disorders after left brain damage.
AB  - In this paper we review studies that investigated tool use disorders in left
      brain damaged (LBD) patients over the last 30 years. Four tasks are classically
      used in the field of apraxia: Pantomime of tool use, single tool use, real tool
      use and mechanical problem solving. Our aim was to address two issues, namely,
      (1) the role of mechanical knowledge in real tool use and (2) the cognitive
      mechanisms underlying pantomime of tool use, a task widely employed by clinicians
      and researchers. To do so, we extracted data from 36 papers and computed the
      difference between healthy subjects and LBD patients. On the whole, pantomime of
      tool use is the most difficult task and real tool use is the easiest one.
      Moreover, associations seem to appear between pantomime of tool use, real tool
      use and mechanical problem solving. These results suggest that the loss of
      mechanical knowledge is critical in LBD patients, even if all of those tasks (and
      particularly pantomime of tool use) might put differential demands on semantic
      memory and working memory. 

PMID- 24904488
TI  - Experimentally induced distraction impacts cognitive but not emotional processes
      in think-aloud cognitive assessment.
AB  - Studies have examined the impact of distraction on basic task performance (e.g.,
      working memory, motor responses), yet research is lacking regarding its impact in
      the domain of think-aloud cognitive assessment, where the threat to assessment
      validity is high. The Articulated Thoughts in Simulated Situations think-aloud
      cognitive assessment paradigm was employed to address this issue. Participants
      listened to scenarios under three conditions (i.e., while answering trivia
      questions, playing a visual puzzle game, or with no experimental distractor).
      Their articulated thoughts were then content-analyzed both by the Linguistic
      Inquiry and Word Count (LIWC) program and by content analysis of emotion and
      cognitive processes conducted by trained coders. Distraction did not impact
      indices of emotion but did affect cognitive processes. Specifically, with the
      LIWC system, the trivia questions distraction condition resulted in significantly
      higher proportions of insight and causal words, and higher frequencies of non
      fluencies (e.g., "uh" or "umm") and filler words (e.g., "like" or "you know").
      Coder-rated content analysis found more disengagement and more misunderstanding
      particularly in the trivia questions distraction condition. A better
      understanding of how distraction disrupts the amount and type of cognitive
      engagement holds important implications for future studies employing cognitive
      assessment methods. 

PMID- 24904490
TI  - Toward a dynamical theory of body movement in musical performance.
AB  - Musicians sway expressively as they play in ways that seem clearly related to the
      music, but quantifying the relationship has been difficult. We suggest that a
      complex systems framework and its accompanying tools for analyzing non-linear
      dynamical systems can help identify the motor synergies involved. Synergies are
      temporary assemblies of parts that come together to accomplish specific goals. We
      assume that the goal of the performer is to convey musical structure and
      expression to the audience and to other performers. We provide examples of how
      dynamical systems tools, such as recurrence quantification analysis (RQA), can be
      used to examine performers' movements and relate them to the musical structure
      and to the musician's expressive intentions. We show how detrended fluctuation
      analysis (DFA) can be used to identify synergies and discover how they are
      affected by the performer's expressive intentions. 

PMID- 24904492
TI  - Predicted causality in decision making: the role of culture.

PMID- 24904489
TI  - Sustained invisibility through crowding and continuous flash suppression: a
      comparative review.
AB  - The study of non-conscious vision benefits from several alternative methods that
      allow the suppression of an image from awareness. Here, we present and compare
      two of them that are particularly well-suited for creating sustained periods of
      invisibility, namely visual crowding and continuous flash suppression (CFS). In
      visual crowding, a peripheral image surrounded by similar flankers becomes
      impossible to discriminate. In CFS, an image presented to one eye becomes
      impossible to detect when rapidly changing patterns are presented to the other
      eye. After discussing the experimental specificities of each method, we give a
      comparative overview of the main empirical results derived from them, from the
      mere analysis of low-level features to the extraction of semantic contents. We
      conclude by proposing practical guidelines and future directions to obtain more
      quantitative and systematic measures of non-conscious processes under prolonged
      stimulation. 

PMID- 24904491
TI  - Mirror-image discrimination in the literate brain: a causal role for the left
      occpitotemporal cortex.
AB  - Previous studies show that the primate and human visual system automatically
      generates a common and invariant representation from a visual object image and
      its mirror reflection. For humans, however, this mirror-image generalization
      seems to be partially suppressed through literacy acquisition, since literate
      adults have greater difficulty in recognizing mirror images of letters than those
      of other visual objects. At the neural level, such category-specific effect on
      mirror-image processing has been associated with the left occpitotemporal cortex
      (L-OTC), but it remains unclear whether the apparent "inhibition" on mirror
      letters is mediated by suppressing mirror-image representations covertly
      generated from normal letter stimuli. Using transcranial magnetic stimulation
      (TMS), we examined how transient disruption of the L-OTC affects mirror-image
      recognition during a same-different judgment task, while varying the semantic
      category (letters and non-letter objects), identity (same or different), and
      orientation (same or mirror-reversed) of the first and second stimuli. We found
      that magnetic stimulation of the L-OTC produced a significant delay in mirror
      image recognition for letter-strings but not for other objects. By contrast, this
      category specific impact was not observed when TMS was applied to other control
      sites, including the right homologous area and vertex. These results thus
      demonstrate a causal link between the L-OTC and mirror-image discrimination in
      literate people. We further suggest that left-right sensitivity for letters is
      not achieved by a local inhibitory mechanism in the L-OTC but probably relies on
      the inter-regional coupling with other orientation-sensitive occipito-parietal
      regions. 

PMID- 24904493
TI  - No smile like another: adult age differences in identifying emotions that
      accompany smiles.
AB  - People smile in various emotional contexts, for example, when they are amused or
      angry or simply being polite. We investigated whether younger and older adults
      differ in how well they are able to identify the emotional experiences
      accompanying smile expressions, and whether the age of the smiling person plays a
      role in this respect. With this aim, we produced 80 video episodes of three types
      of smile expressions: positive-affect smiles had been spontaneously displayed by
      target persons as they were watching amusing film clips and cartoons. Negative
      affect smiles had been displayed spontaneously by target persons during an
      interaction in which they were being unfairly accused. Affectively neutral smiles
      were posed upon request. Differences in the accompanying emotional experiences
      were validated by target persons' self-reports. These smile videos served as
      experimental stimuli in two studies with younger and older adult participants. In
      Study 1, older participants were less likely to attribute positive emotions to
      smiles, and more likely to assume that a smile was posed. Furthermore, younger
      participants were more accurate than older adults at identifying emotional
      experiences accompanying smiles. In Study 2, both younger and older participants
      attributed positive emotions more frequently to smiles shown by older as compared
      to younger target persons, but older participants did so less frequently than
      younger participants. Again, younger participants were more accurate than older
      participants in identifying emotional experiences accompanying smiles, but this
      effect was attenuated for older target persons. Older participants could better
      identify the emotional state accompanying smiles shown by older than by younger
      target persons. Taken together, these findings indicate that there is an age
      related decline in the ability to decipher the emotional meaning of smiles
      presented without context, which, however, is attenuated when the smiling person
      is also an older adult. 

PMID- 24904494
TI  - A feed-forward spiking model of shape-coding by IT cells.
AB  - The ability to recognize a shape is linked to figure-ground (FG) organization.
      Cell preferences appear to be correlated across contrast-polarity reversals and
      mirror reversals of polygon displays, but not so much across FG reversals. Here
      we present a network structure which explains both shape-coding by simulated IT
      cells and suppression of responses to FG reversed stimuli. In our model FG
      segregation is achieved before shape discrimination, which is itself evidenced by
      the difference in spiking onsets of a pair of output cells. The studied example
      also includes feature extraction and illustrates a classification of binary
      images depending on the dominance of vertical or horizontal borders. 

PMID- 24904495
TI  - Spatially rearranged object parts can facilitate perception of intact whole
      objects.
AB  - The familiarity of an object depends on the spatial arrangement of its parts;
      when the parts are spatially rearranged, they form a novel, unrecognizable
      configuration. Yet the same collection of parts comprises both the familiar and
      novel configuration. Is it possible that the collection of familiar parts
      activates a representation of the intact familiar configuration even when they
      are spatially rearranged? We presented novel configurations as primes before test
      displays that assayed effects on figure-ground perception from memories of intact
      familiar objects. In our test displays, two equal-area regions shared a central
      border; one region depicted a portion of a familiar object. Previous research
      with such displays has shown that participants are more likely to perceive the
      region depicting a familiar object as the figure and the abutting region as its
      ground when the familiar object is depicted in its upright orientation rather
      than upside down. The novel primes comprised either the same or a different
      collection of parts as the familiar object in the test display (part-rearranged
      and control primes, respectively). We found that participants were more likely to
      perceive the familiar region as figure in upright vs. inverted displays following
      part-rearranged primes but not control primes. Thus, priming with a novel
      configuration comprising the same familiar parts as the upcoming figure-ground
      display facilitated orientation-dependent effects of object memories on figure
      assignment. Similar results were obtained when the spatially rearranged
      collection of parts was suggested on the groundside of the prime's border,
      suggesting that familiar parts in novel configurations access the representation
      of their corresponding intact whole object before figure assignment. These data
      demonstrate that familiar parts access memories of familiar objects even when
      they are arranged in a novel configuration. 

PMID- 24904496
TI  - Is a bird in the hand worth two in the future? Intertemporal choice, attachment
      and theory of mind in school-aged children.
AB  - Intertemporal choice is a decision-making dilemma related to outcomes of
      different entity located at different time points. Economic and psychological
      literature on this topic showed the phenomen of temporal discounting, i.e., the
      proclivity to devalue the outcome distant in time on the basis of the time delay
      necessary to obtain it. The goals of this research are to investigate two
      different components of intertemporal choice separately, namely time and outcome,
      in school-age children, and the possible link among such components and the
      security of attachment style and theory of mind. Ninety one children aged between
      6 and 10 years performed two intertemporal choice tasks, first and second order
      false belief tasks and the Separation Anxiety Task in the Family and School
      versions. Results showed that the two components of intertemporal choice (waiting
      tolerance and sensitivity to delayed outcome) are stately interrelated; the
      quality of the attachment to the family caregiver affects the tolerance to
      waiting time and first order false belief understanding affects both the
      components of intertemporal choice. 

PMID- 24904497
TI  - How sensory-motor systems impact the neural organization for language: direct
      contrasts between spoken and signed language.
AB  - To investigate the impact of sensory-motor systems on the neural organization for
      language, we conducted an H2 (15)O-PET study of sign and spoken word production
      (picture-naming) and an fMRI study of sign and audio-visual spoken language
      comprehension (detection of a semantically anomalous sentence) with hearing
      bilinguals who are native users of American Sign Language (ASL) and English.
      Directly contrasting speech and sign production revealed greater activation in
      bilateral parietal cortex for signing, while speaking resulted in greater
      activation in bilateral superior temporal cortex (STC) and right frontal cortex,
      likely reflecting auditory feedback control. Surprisingly, the language
      production contrast revealed a relative increase in activation in bilateral
      occipital cortex for speaking. We speculate that greater activation in visual
      cortex for speaking may actually reflect cortical attenuation when signing, which
      functions to distinguish self-produced from externally generated visual input.
      Directly contrasting speech and sign comprehension revealed greater activation in
      bilateral STC for speech and greater activation in bilateral occipital-temporal
      cortex for sign. Sign comprehension, like sign production, engaged bilateral
      parietal cortex to a greater extent than spoken language. We hypothesize that
      posterior parietal activation in part reflects processing related to spatial
      classifier constructions in ASL and that anterior parietal activation may reflect
      covert imitation that functions as a predictive model during sign comprehension.
      The conjunction analysis for comprehension revealed that both speech and sign
      bilaterally engaged the inferior frontal gyrus (with more extensive activation on
      the left) and the superior temporal sulcus, suggesting an invariant bilateral
      perisylvian language system. We conclude that surface level differences between
      sign and spoken languages should not be dismissed and are critical for
      understanding the neurobiology of language. 

PMID- 24904498
TI  - Never too late? An advantage on tests of auditory attention extends to late
      bilinguals.
AB  - Recent studies, using predominantly visual tasks, indicate that early bilinguals
      tend to outperform monolinguals on attention tests. It remains less clear whether
      such advantages extend to those bilinguals who have acquired their second
      language later in life. We examined this question in 38 monolingual and 60
      bilingual university students. The bilingual group was further subdivided into
      early childhood (ECB), late childhood (LCB), and early adulthood bilinguals
      (EAB). The assessment consisted of five subtests from the clinically validated
      Test of Everyday Attention (TEA). Overall, bilinguals outperformed monolinguals
      on auditory attention tests, but not on visual search tasks. The latter
      observation suggests that the differences between bilinguals and monolinguals are
      specific and not due to a generally higher cognitive performance in bilinguals.
      Within the bilingual group, ECB showed a larger advantage on attention switching,
      LCB/EAB on selective attention. We conclude that the effects of bilingualism
      extend into the auditory domain and are not confined to childhood bilinguals,
      although their scope might be slightly different in early and late bilinguals. 

PMID- 24904499
TI  - Attachment to inanimate objects and early childcare: A twin study.
AB  - Extensive non-maternal childcare plays an important role in children's
      development. This study examined a potential coping mechanism for dealing with
      daily separation from caregivers involved in childcare experience - children's
      development of attachments toward inanimate objects. We employed the twin design
      to estimate relative environmental and genetic contributions to the presence of
      object attachment, and assess whether childcare explains some of the
      environmental variation in this developmental phenomenon. Mothers reported about
      1122 3-year-old twin pairs. Variation in object attachment was accounted for by
      heritability (48%) and shared environment (48%), with childcare quantity
      accounting for 2.2% of the shared environment effect. Children who spent half
      days in childcare were significantly less likely to attach to objects relative to
      children who attended full-day childcare. 

PMID- 24904500
TI  - Relations between executive function and emotionality in preschoolers: Exploring
      a transitive cognition-emotion linkage.
AB  - Emotions play a crucial role in appraisal of experiences and environments and in
      guiding thoughts and actions. Moreover, executive function (EF) and emotion
      regulation (ER) have received much attention, not only for positive associations
      with children's social-emotional functioning, but also for potential central
      roles in cognitive functioning. In one conceptualization of ER (Campos etal.,
      2004), processes of ER, and those of emotional expression and experience
      (hereafter referred to as emotionality) are highly related and reciprocal; yet,
      there has been little research on young children's EF that focuses on
      emotionality, although it is easily observed within a classroom. The two goals of
      the study were to: (1) investigate the relatively unexplored role of emotionality
      in the development of EF in early childhood and (2) assess the relations between
      an observational rating of EF obtained after direct assessment with a
      standardized EF rating scale. We predicted that observed emotionality and EF
      would both demonstrate stability and predict one another within and across time.
      175 children aged 35-60 months were recruited from Head Start and private
      childcare centers. Using partial least squares modeling, we chose T1 emotionality
      as the exogenous variable and tested pathways between emotionality and EF across
      two time points, 6 months apart. Results showed that both T1 observed EF and
      emotionality predicted their respective T2 counterparts, supporting the idea that
      both constructs build upon existing systems. Further, T1 emotionality predicted
      T1 observed EF and the T2 BRIEF-P composite. In turn, T1 observed EF predicted
      emotionality and the T2 BRIEF-P composite. These findings fit with literature on
      older populations in which EF and emotionality have been related, yet are the
      first to report such relations in early childhood. Last, T1 observed EF's
      positive prediction of the T2 BRIEF-P composite lends credence to the use of both
      EF measures in applied and research settings. 

PMID- 24904501
TI  - Development and necessary norms of reasoning.
AB  - The question of whether reasoning can, or should, be described by a single
      normative model is an important one. In the following, I combine epistemological
      considerations taken from Piaget's notion of genetic epistemology, a hypothesis
      about the role of reasoning in communication and developmental data to argue that
      some basic logical principles are in fact highly normative. I argue here that
      explicit, analytic human reasoning, in contrast to intuitive reasoning, uniformly
      relies on a form of validity that allows distinguishing between valid and invalid
      arguments based on the existence of counterexamples to conclusions. 

PMID- 24904502
TI  - An asymmetric inhibition model of hemispheric differences in emotional
      processing.
AB  - Two relatively independent lines of research have addressed the role of the
      prefrontal cortex in emotional processing. The first examines hemispheric
      asymmetries in frontal function; the second focuses on prefrontal interactions
      between cognition and emotion. We briefly review each perspective and highlight
      inconsistencies between them. We go on to describe an alternative model that
      integrates approaches by focusing on hemispheric asymmetry in inhibitory
      executive control processes. The asymmetric inhibition model proposes that right
      lateralized executive control inhibits processing of positive or approach-related
      distractors, and left-lateralized control inhibits negative or withdrawal-related
      distractors. These complementary processes allow us to maintain and achieve
      current goals in the face of emotional distraction. We conclude with a research
      agenda that uses the model to generate novel experiments that will advance our
      understanding of both hemispheric asymmetries and cognition-emotion interactions.

PMID- 24904504
TI  - The emergence of use of a rake-like tool: a longitudinal study in human infants.
AB  - We describe the results of a longitudinal study on five infants from age 12 to 20
      months, presented with an out of reach toy and a rake-like tool within reach.
      Five conditions of spatial relationship between toy and rake were tested.
      Outcomes and types of behavior were analyzed. There were successes observed
      around 12 months in the condition of spatial contiguity between rake and toy, but
      these could not be interpreted as corresponding to full understanding of the use
      of the rake. At this age and for the following months, in the conditions
      involving spatial separation between rake and toy, infants' strategies fluctuated
      between paying attention to the toy only, exploring the rake for its own sake,
      and connecting rake and toy but with no apparent attempt to bring the toy closer.
      Only between 16 and 20 months did infants fairly suddenly start to intentionally
      try to bring the toy closer with the tool: at this stage the infants also became
      able to learn from their failures and to correct their actions, as well as to
      benefit from demonstration from an adult. We examine the individual differences
      in the pattern of change in behaviors leading to tool use in the five infants,
      and find no increase in any one type of behavior that systematically precedes
      success. We conclude that sudden success at 18 months probably corresponds to the
      coming together of a variety of capacities. 

PMID- 24904503
TI  - Attention and word learning in autistic, language delayed and typically
      developing children.
AB  - Previous work has demonstrated that patterns of social attention hold predictive
      value for language development in typically developing infants. The goal of this
      research was to explore how patterns of attention in autistic, language delayed,
      and typically developing children relate to early word learning and language
      abilities. We tracked patterns of eye movements to faces and objects while
      children watched videos of a woman teaching them a series of new words.
      Subsequent test trials measured participants' recognition of these novel word
      object pairings. Results indicated that greater attention to the speaker's mouth
      was related to higher scores on standardized measures of language development for
      autistic and typically developing children (but not for language delayed
      children). This effect was mediated by age for typically developing, but not
      autistic children. When effects of age were controlled for, attention to the
      mouth among language delayed participants was negatively correlated with
      standardized measures of language learning. Attention to the speaker's mouth and
      eyes while she was teaching the new words was also predictive of faster
      recognition of those words among autistic children. These results suggest that
      language delays among children with autism may be driven in part by aberrant
      social attention, and that the mechanisms underlying these delays may differ from
      those in language delayed participants without autism. 

PMID- 24904505
TI  - ERP topographic analyses from concept to articulation in word production studies.
AB  - Most ERP studies using overt speech production tasks have analyzed fixed time
      windows of stimulus-aligned ERPs, not exceeding the fastest production latency.
      These fixed ERP time-windows may cover the whole speech planning process for fast
      trials or participants, but only part of the planning processes for trials or
      participants with production latencies exceeding the analyzed period. Two core
      questions thus emerge when analysing fixed time-windows in overt language
      production, namely (1) to what extent do ERPs capture "later" encoding processes,
      especially phonological and phonetic encoding, and (2) how to account for
      different production latencies across conditions or individuals. Here we review a
      methodological approach combining waveform and topographic analyses on integrated
      stimulus- and response-aligned ERPs according to response latencies in each
      participant and condition. Then we illustrate the approach with a picture naming
      task. Crucially for the purpose of the methodological illustration, the separate
      analysis of fixed stimulus- and response-locked ERPs led to a counter-intuitive
      result (longer lasting periods of stable global electrophysiological activity for
      the fastest condition). Coherent results with longer lasting periods of
      topographic stability in the slower condition only appeared when combining
      stimulus- and response-aligned ERPs in order to cover the actual word planning
      time-windows. Thus this combined analysis enabled to disentangle the possible
      interpretations of the neurophysiological processes underlying differences across
      conditions observed on waveforms and on topographies in the fixed ERP periods. 

PMID- 24904507
TI  - Assimilation and contrast effects in suboptimal affective priming paradigm.

PMID- 24904506
TI  - The specificity of action knowledge in sensory and motor systems.
AB  - Neuroimaging studies have found that sensorimotor systems are engaged when
      participants observe actions or comprehend action language. However, most of
      these studies have asked the binary question of whether action concepts are
      embodied or not, rather than whether sensory and motor areas of the brain contain
      graded amounts of information during putative action simulations. To address this
      question, we used repetition suppression (RS) functional magnetic resonance
      imaging to determine if functionally-localized motor movement and visual motion
      regions-of-interest (ROI) and two anatomical ROIs (inferior frontal gyrus, IFG;
      left posterior middle temporal gyrus, pMTG) were sensitive to changes in the
      exemplar (e.g., two different people "kicking") or representational format (e.g.,
      photograph or schematic drawing of someone "kicking") within pairs of action
      images. We also investigated whether concrete versus more symbolic depictions of
      actions (i.e., photographs or schematic drawings) yielded different patterns of
      activation throughout the brain. We found that during a conceptual task, sensory
      and motor systems represent actions at different levels of specificity. While the
      visual motion ROI did not exhibit RS to different exemplars of the same action or
      to the same action depicted by different formats, the motor movement ROI did.
      These effects are consistent with "person-specific" action simulations: if the
      motor system is recruited for action understanding, it does so by activating
      one's own motor program for an action. We also observed significant repetition
      enhancement within the IFG ROI to different exemplars or formats of the same
      action, a result that may indicate additional cognitive processing on these
      trials. Finally, we found that the recruitment of posterior brain regions by
      action concepts depends on the format of the input: left lateral occipital cortex
      and right supramarginal gyrus responded more strongly to symbolic depictions of
      actions than concrete ones. 

PMID- 24904508
TI  - Exploring the effects of suboptimal affective priming: enhancement and
      minimization.

PMID- 24904509
TI  - Phonetic detail in German syllable pronunciation: influences of prosody and
      grammar.
AB  - This study presents two experiments designed to disentangle various influences on
      syllable pronunciation. Target syllables were embedded in carrier sentences, read
      aloud by native German participants, and analyzed in terms of syllable and vowel
      duration, acoustic prominence, and spectral similarity. Both experiments revealed
      a complex interaction of different factors, as participants attempted to
      disambiguate semantically and syntactically ambiguous structures while at the
      same time distinguishing between important and unimportant information. The first
      experiment examined German verb prefixes that formed prosodic minimal pairs.
      Carrier sentences were formulated so as to systematically vary word stress,
      sentence focus, and the type of syntactic boundary following the prefix. We found
      clear effects of word stress on duration, prominence, and spectral similarity as
      well as a small influence of sentence focus on prominence levels of lexically
      stressed prefixes. While sentence boundaries were marked by particularly high
      prominence and duration values, hardly any effect was shown for word boundaries.
      The second experiment compared German function words which were segmentally
      identical but appeared in different grammatical roles. Here, definite articles
      were found to be shorter than relative pronouns and still shorter than
      demonstrative pronouns. As definite articles are also much more common than the
      other two lexical classes, effects of lemma frequency might also have played a
      role. 

PMID- 24904510
TI  - Reduced empathic concern leads to utilitarian moral judgments in trait
      alexithymia.
AB  - Recent research with moral dilemmas supports dual-process model of moral decision
      making. This model posits two different paths via which people can endorse
      utilitarian solution that requires personally harming someone in order to achieve
      the greater good (e.g., killing one to save five people): (i) weakened emotional
      aversion to the prospect of harming someone due to reduced empathic concern for
      the victim; (ii) enhanced cognition which supports cost-benefit analysis and
      countervails the prepotent emotional aversion to harm. Direct prediction of this
      model would be that personality traits associated with reduced empathy would show
      higher propensity to endorse utilitarian solutions. As per this prediction, we
      found that trait alexithymia, which is well-known to have deficits in empathy,
      was indeed associated with increased utilitarian tendencies on emotionally
      aversive personal moral dilemmas and this was due to reduced empathic concern for
      the victim. Results underscore the importance of empathy for moral judgments in
      harm/care domain of morality. 

PMID- 24904512
TI  - How (not) to argue about is/ought inferences in the cognitive sciences.

PMID- 24904511
TI  - Is crying a self-soothing behavior?
AB  - This contribution describes the current state-of-the-art of the scientific
      literature regarding the self-soothing effects of crying. Starting from the
      general hypothesis that crying is a self-soothing behavior, we consider different
      mechanisms through which these effects may appear. In the first section, we
      briefly explain the main functions of human crying. Then we define self-soothing
      in terms of homeostatic processes of mood regulation and stress reduction and we
      underline the importance of distinguishing self-soothing effects of crying from
      social-soothing that it may elicit. We then provide a comprehensive review of the
      putative mood-enhancing and -relieving effects of crying and their variations
      stemming from characteristics of crying person, antecedents, manifestations, and
      social consequences of crying. We also discuss the possible methodological
      explanations for the seemingly discrepant findings regarding mood improvement and
      relief that may follow crying. We then provide theoretical and empirical support
      for our general hypothesis that crying is a self-soothing behavior by presenting
      and evaluating the possible physiological, cognitive, and behavioral mechanisms
      that may play a mediating role in the relationship between crying and homeostatic
      regulation that includes mood improvement and relief. Starting from the idea that
      social-soothing and self-soothing mechanisms share the same physiological
      systems, we propose that biological processes act in parallel with learning and
      reappraisal processes that accompany crying, which results in homeostatic
      regulation. Given the parallels between self-soothing behaviors in humans and
      animals, we also propose that crying might self-soothe through a mechanism that
      shares key properties with rhythmical, stereotypic behaviors. We conclude that,
      in addition to the importance of socially mediated mechanisms for the mood
      enhancing effects of crying, there is converging evidence for the direct, self
      soothing effects of crying. 

PMID- 24904513
TI  - Developing embodied cognition: insights from children's concepts and language
      processing.
AB  - Over the past decade, theories of embodied cognition have become increasingly
      influential with research demonstrating that sensorimotor experiences are
      involved in cognitive processing; however, this embodied research has primarily
      focused on adult cognition. The notion that sensorimotor experience is important
      for acquiring conceptual knowledge is not a novel concept for developmental
      researchers, and yet theories of embodied cognition often do not fully integrate
      developmental findings. We propose that in order for an embodied cognition
      perspective to be refined and advanced as a lifelong theory of cognition, it is
      important to consider what can be learned from research with children. In this
      paper, we focus on development of concepts and language processing, and examine
      the importance of children's embodied experiences for these aspects of cognition
      in particular. Following this review, we outline what we see as important
      developmental issues that need to be addressed in order to determine the extent
      to which language and conceptual knowledge are embodied and to refine theories of
      embodied cognition. 

PMID- 24904515
TI  - The long is not just a sum of the shorts: on time experienced and other times.

PMID- 24904514
TI  - Affective and contextual values modulate spatial frequency use in object
      recognition.
AB  - Visual object recognition is of fundamental importance in our everyday
      interaction with the environment. Recent models of visual perception emphasize
      the role of top-down predictions facilitating object recognition via initial
      guesses that limit the number of object representations that need to be
      considered. Several results suggest that this rapid and efficient object
      processing relies on the early extraction and processing of low spatial
      frequencies (LSF). The present study aimed to investigate the SF content of
      visual object representations and its modulation by contextual and affective
      values of the perceived object during a picture-name verification task. Stimuli
      consisted of pictures of objects equalized in SF content and categorized as
      having low or high affective and contextual values. To access the SF content of
      stored visual representations of objects, SFs of each image were then randomly
      sampled on a trial-by-trial basis. Results reveal that intermediate SFs between
      14 and 24 cycles per object (2.3-4 cycles per degree) are correlated with fast
      and accurate identification for all categories of objects. Moreover, there was a
      significant interaction between affective and contextual values over the SFs
      correlating with fast recognition. These results suggest that affective and
      contextual values of a visual object modulate the SF content of its internal
      representation, thus highlighting the flexibility of the visual recognition
      system. 

PMID- 24904516
TI  - Primary Motor Cortex Neurons during Individuated Finger and Wrist Movements:
      Correlation of Spike Firing Rates with the Motion of Individual Digits versus
      Their Principal Components.
AB  - The joints of the hand provide 24 mechanical degrees of freedom. Yet 2-7
      principal components (PCs) account for 80-95% of the variance in hand joint
      motion during tasks that vary from grasping to finger spelling. Such findings
      have led to the hypothesis that the brain may simplify operation of the hand by
      preferentially controlling PCs. We tested this hypothesis using data recorded
      from the primary motor cortex (M1) during individuated finger and wrist
      movements. Principal component analysis (PCA) of the simultaneous position of the
      five digits and the wrist showed relatively consistent kinematic synergies across
      recording sessions in two monkeys. The first three PCs typically accounted for
      85% of the variance. Cross-correlations then were calculated between the firing
      rate of single neurons and the simultaneous flexion/extension motion of each of
      the five digits and the wrist, as well as with each of their six PCs. For each
      neuron, we then compared the maximal absolute value of the cross-correlations
      (MAXC) achieved with the motion of any digit or the wrist to the MAXC achieved
      with motion along any PC axis. The MAXC with a digit and the MAXC with a PC were
      themselves highly correlated across neurons. A minority of neurons correlated
      more strongly with a PC than with any digit. But for the populations of neurons
      sampled from each of two subjects, MAXCs with digits were slightly but
      significantly higher than those with PCs. We therefore reject the hypothesis that
      M1 neurons preferentially control PCs of hand motion. We cannot exclude the
      possibility that M1 neurons might control kinematic synergies identified using
      linear or non-linear methods other than PCA. We consider it more likely, however,
      that neurons in other centers of the motor system - such as the pontomedullary
      reticular formation and the spinal gray matter - drive synergies of movement
      and/or muscles, which M1 neurons act to fractionate in producing individuated
      finger and wrist movements. 

PMID- 24904517
TI  - Treatment of intracranial vasospasm following subarachnoid hemorrhage.
AB  - Vasospasm has been a long known source of delayed morbidity and mortality in
      aneurysmal subarachnoid hemorrhage patients. Delayed ischemic neurologic deficits
      associated with vasospasm may account for as high as 50% of the deaths in
      patients who survive the initial period after aneurysm rupture and its treatment.
      The diagnosis and treatment of vasospasm has still been met with some
      controversy. It is clear that subarachnoid hemorrhage is best cared for in
      tertiary care centers with modern resources and access to cerebral angiography.
      Ultimately, a high degree of suspicion for vasospasm must be kept during ICU
      care, and any signs or symptoms must be investigated and treated immediately to
      avoid permanent stroke and neurologic deficit. Treatment for vasospasm can occur
      through both ICU intervention and endovascular administration of intra-arterial
      vasodilators and balloon angioplasty. The best outcomes are often attained when
      these methods are used in conjunction. The following article reviews the
      literature on cerebral vasospasm and its treatment and provides the authors'
      approach to treatment of these patients. 

PMID- 24904518
TI  - Distinct neuropsychological correlates of cognitive, behavioral, and affective
      apathy sub-domains in acquired brain injury.
AB  - Apathy has a high prevalence and a significant contribution to treatment and
      rehabilitation outcomes in acquired brain damage. Research on the disorder's
      neuropsychological correlates has produced mixed results. While the mixed picture
      may be due to the use of varied assessment tools on different patient
      populations, it is also the case that most studies treat apathy as a unitary
      syndrome. This is despite the evidence that apathy is a multifaceted and
      multidimensional syndrome. This study investigates the neuropsychological
      correlates of apathy in 49 patients with acquired brain damage. It further
      fractionates apathy symptoms into affective, cognitive, and behavioral sub
      domains and investigates their individual relations with standard measures of
      affective, cognitive, and behavioral functioning. Global apathy scores were not
      related to any of these measures. Affective apathy was associated with emotion
      perception deficits, and cognitive apathy was associated with executive deficits
      on the Brixton test. These results demonstrate that treating apathy as a single
      entity may hide important correlates to apathy symptoms that become visible when
      the disorder is fractionated into its sub-domains. The study highlights the
      research and clinical importance of treating apathy as a multidimensional
      syndrome. 

PMID- 24904519
TI  - Kinematics of the Reach-to-Grasp Movement in Vascular Parkinsonism: A Comparison
      with Idiopathic Parkinson's Disease Patients.
AB  - The performance of patients with vascular parkinsonism (VPD) on a reach-to-grasp
      task was compared with that of patients affected by idiopathic Parkinson's
      disease (IPD) and age-matched control subjects. The aim of the study was to
      determine how patients with VPD and IPD compare at the level of the kinematic
      organization of prehensile actions. We examined how subjects concurrently
      executed the transport and grasp components of reach-to-grasp movements when
      grasping differently sized objects. When comparing both VPD and IPD groups to
      control subjects, all patients showed longer movement duration and smaller hand
      opening, reflecting bradykinesia and hypometria, respectively. Furthermore, for
      all patients, the onset of the manipulation component was delayed with respect to
      the onset of the transport component. However, for patients with VPD this delay
      was significantly smaller than that found for the IPD group. It is proposed that
      this reflects a deficit - which is moderate for VPD as compared to IPD patients -
      in the simultaneous (or sequential) implementation of different segments of a
      complex movement. Altogether these findings suggest that kinematic analysis of
      reach-to-grasp movement has the ability to provide potential instruments to
      characterize different forms of parkinsonism. 

PMID- 24904520
TI  - The Sub-Classification of Amnestic Mild Cognitive Impairment Using MRI-Based
      Cortical Thickness Measures.
AB  - BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered to be the
      transitional stage between healthy aging and Alzheimer's disease (AD). Moreover,
      aMCI individuals with additional impairment in one or more non-memory cognitive
      domains are at higher risk of conversion to AD. Hence accurate identification of
      the sub-types of aMCI would enable earlier detection of individuals progressing
      to AD. METHODS: We examine the group differences in cortical thickness between
      single-domain and multiple-domain sub-types of aMCI, and as well as with respect
      to age-matched controls in a well-balanced cohort from the Sydney Memory and
      Aging Study. In addition, the diagnostic value of cortical thickness in the sub
      classification of aMCI as well as from normal controls using support vector
      machine (SVM) classifier is evaluated, using a novel cross-validation technique
      that can handle class-imbalance. RESULTS: This study revealed an increased, as
      well as a wider spread, of cortical thinning in multiple-domain aMCI compared to
      single-domain aMCI. The best performances of the classifier for the pairs (1)
      single-domain aMCI and normal controls, (2) multiple-domain aMCI and normal
      controls, and (3) single and multiple-domain aMCI were AUC = 0.52, 0.66, and
      0.54, respectively. The accuracy of the classifier for the three pairs was just
      over 50% exhibiting low specificity (44-60%) and similar sensitivity (53-68%).
      CONCLUSION: Analysis of group differences added evidence to the hypothesis that
      multiple-domain aMCI is a later stage of AD compared to single-domain aMCI. The
      classification results show that discrimination among single, multiple-domain sub
      types of aMCI and normal controls is limited using baseline cortical thickness
      measures.

PMID- 24904521
TI  - Cytomorphometric Changes in Hippocampal CA1 Neurons Exposed to Simulated
      Microgravity Using Rats as Model.
AB  - Microgravity and sleep loss lead to cognitive and learning deficits. These
      behavioral alterations are likely to be associated with cytomorphological changes
      and loss of neurons. To understand the phenomenon, we exposed rats (225-275 g) to
      14 days simulated microgravity (SMg) and compared its effects on CA1 hippocampal
      neuronal plasticity, with that of normal cage control rats. We observed that the
      mean area, perimeter, synaptic cleft, and length of active zone of CA1
      hippocampal neurons significantly decreased while dendritic arborization and
      number of spines significantly increased in SMg group as compared with controls.
      The mean thickness of the postsynaptic density and total dendritic length
      remained unaltered. The changes may be a compensatory effect induced by exposure
      to microgravity; however, the effects may be transient or permanent, which need
      further study. These findings may be useful for designing effective prevention
      for those, including the astronauts, exposed to microgravity. Further, subject to
      confirmation, we propose that SMg exposure might be useful for recovery of stroke
      patients. 

PMID- 24904522
TI  - Serotonin System Implication in l-DOPA-Induced Dyskinesia: From Animal Models to
      Clinical Investigations.
AB  - In the recent years, the serotonin system has emerged as a key player in the
      induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson's
      disease. In fact, serotonin neurons possess the enzymatic machinery able to
      convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and
      release. However, serotonin neurons lack a feedback control mechanism able to
      regulate synaptic DA levels. While in a situation of partial DA depletion spared
      DA terminals can buffer DA released from serotonin neurons, the progression of DA
      neuron degeneration impairs this protective mechanism, causing swings in synaptic
      DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with
      this view, removal of serotonin neurons by selective toxin, or pharmacological
      silencing of their activity, produced complete suppression of LID in animal
      models of Parkinson's disease. In this article, we will revise the experimental
      evidence pointing to the important role of serotonin neurons in dyskinesia, and
      we will discuss the clinical implications. 

PMID- 24904523
TI  - Insulin-Like Growth Factor Receptor Signaling is Necessary for Epidermal Growth
      Factor Mediated Proliferation of SVZ Neural Precursors in vitro Following
      Neonatal Hypoxia-Ischemia.
AB  - In this study, we assessed the importance of insulin-like growth factor (IGF) and
      epidermal growth factor (EGF) receptor co-signaling for rat neural precursor (NP)
      cell proliferation and self-renewal in the context of a developmental brain
      injury that is associated with cerebral palsy. Consistent with previous studies,
      we found that there is an increase in the in vitro growth of subventricular zone
      NPs isolated acutely after cerebral hypoxia-ischemia; however, when cultured in
      medium that is insufficient to stimulate the IGF type 1 receptor, neurosphere
      formation and the proliferative capacity of those NPs was severely curtailed.
      This reduced growth capacity could not be attributed simply to failure to
      survive. The growth and self-renewal of the NPs could be restored by addition of
      both IGF-I and IGF-II. Since the size of the neurosphere is predominantly due to
      cell proliferation we hypothesized that the IGFs were regulating progression
      through the cell cycle. Analyses of cell cycle progression revealed that IGF-1R
      activation together with EGFR co-signaling decreased the percentage of cells in
      G1 and enhanced cell progression into S and G2. This was accompanied by increases
      in expression of cyclin D1, phosphorylated histone 3, and phosphorylated Rb.
      Based on these data, we conclude that coordinate signaling between the EGF
      receptor and the IGF type 1 receptor is necessary for the normal proliferation of
      NPs as well as for their reactive expansion after injury. These data indicate
      that manipulations that maintain or amplify IGF signaling in the brain during
      recovery from developmental brain injuries will enhance the production of new
      brain cells to improve neurological function in children who are at risk for
      developing cerebral palsy. 

PMID- 24904524
TI  - Young Adults' Sleep Duration on Work Days: Differences between East and West.
AB  - Human sleep schedules vary widely across countries. We investigated whether these
      variations were related to differences in social factors, Morningness-Eveningness
      (ME) preference, or the natural light-dark cycle by contrasting the sleep
      duration and timing of young adults (age: 18-35 years) on work and free days in
      Singapore (n = 1898) and the UK (n = 837). On work days, people in Singapore had
      later bedtimes, but wake times were similar to the UK sample, resulting in
      shorter sleep duration. In contrast, sleep duration on free days did not differ
      between the two countries. Shorter sleep on work days, without compensatory extra
      long sleep hours on free days, suggest greater demands from work and study in
      Singapore. While the two samples differed slightly in ME preference, the
      associations between eveningness preference and greater extension in sleep
      duration as well as delays in sleep timing on free days were similar in the two
      countries. Thus, differences in ME preference did not account for the differences
      in sleep schedules between the two countries. The greater variability in the
      photoperiod in the UK was not associated with more prominent seasonal changes in
      sleep patterns compared to Singapore. Furthermore, in the UK, daylight saving
      time did not alter sleep schedules relative to clock time. Collectively, these
      findings suggest that differences in social demands, primarily from work or
      study, could account for the observed differences in sleep schedules between
      countries, and that in industrialized societies, social zeitgebers, which
      typically involve exposure to artificial light, are major determinants of sleep
      schedules. 

PMID- 24904525
TI  - Hypothalamic response to the chemo-signal androstadienone in gender dysphoric
      children and adolescents.
AB  - The odorous steroid androstadienone, a putative male chemo-signal, was previously
      reported to evoke sex differences in hypothalamic activation in adult
      heterosexual men and women. In order to investigate whether puberty modulated
      this sex difference in response to androstadienone, we measured the hypothalamic
      responsiveness to this chemo-signal in 39 pre-pubertal and 41 adolescent boys and
      girls by means of functional magnetic resonance imaging. We then investigated
      whether 36 pre-pubertal children and 38 adolescents diagnosed with gender
      dysphoria (GD; DSM-5) exhibited sex-atypical (in accordance with their
      experienced gender), rather than sex-typical (in accordance with their natal sex)
      hypothalamic activations during olfactory stimulation with androstadienone. We
      found that the sex difference in responsiveness to androstadienone was already
      present in pre-pubertal control children and thus likely developed during early
      perinatal development instead of during sexual maturation. Adolescent girls and
      boys with GD both responded remarkably like their experienced gender, thus sex
      atypical. In contrast, pre-pubertal girls with GD showed neither a typically male
      nor female hypothalamic activation pattern and pre-pubertal boys with GD had
      hypothalamic activations in response to androstadienone that were similar to
      control boys, thus sex-typical. We present here a unique data set of boys and
      girls diagnosed with GD at two different developmental stages, showing that these
      children possess certain sex-atypical functional brain characteristics and may
      have undergone atypical sexual differentiation of the brain. 

PMID- 24904526
TI  - Thyroid hormone role on cerebellar development and maintenance: a perspective
      based on transgenic mouse models.
AB  - Cerebellum development is sensitive to thyroid hormone (TH) levels, as THs
      regulate neuronal migration, differentiation, and myelination. Most effects of
      THs are mediated by the thyroid hormone receptor (TR) isoforms TRbeta1, TRbeta2,
      and TRalpha1. Studies aimed at identifying TH target genes during cerebellum
      development have only achieved partial success, as some of these genes do not
      possess classical TH-responsive elements, and those that do are likely to be
      temporally and spatially regulated by THs. THs may also affect neurodevelopment
      by regulating transcription factors that control particular groups of genes.
      Furthermore, TH action can also be affected by TH transport, which is mediated
      mainly by monocarboxylate transporter family members. Studies involving
      transgenic animal models and genome-wide expression analyses have helped to
      address the unanswered questions regarding the role of TH in cerebellar
      development. Recently, a growing body of evidence has begun to clarify the
      molecular, cellular, and functional aspects of THs in the developing cerebellum.
      This review describes the current findings concerning the effects of THs on
      cerebellar development and maintenance as well as advances in the genetic animal
      models used in this field. 

PMID- 24904528
TI  - The central mechanisms of secretin in regulating multiple behaviors.
AB  - Secretin (SCT) was firstly discovered as a gut peptide hormone in stimulating
      pancreatic secretion, while its novel neuropeptide role has drawn substantial
      research interests in recent years. SCT and its receptor (SCTR) are widely
      expressed in different brain regions, where they exert multiple cellular
      functions including neurotransmission, gene expression regulation, neurogenesis,
      and neural protection. As all these neural functions ultimately can affect
      behaviors, it is hypothesized that SCT controls multiple behavioral paradigms.
      Current findings support this hypothesis as SCT-SCTR axis participates in
      modulating social interaction, spatial learning, water and food intake, motor
      coordination, and motor learning behaviors. This mini-review focuses on various
      aspects of SCT and SCTR in hippocampus, hypothalamus, and cerebellum including
      distribution profiles, cellular functions, and behavioral phenotypes to elucidate
      the link between cellular mechanisms and behavioral control. 

PMID- 24904527
TI  - The IGF Hormonal Network in Endometrial Cancer: Functions, Regulation, and
      Targeting Approaches.
AB  - Epidemiological as well as clinical and experimental data identified the insulin
      like growth factors (IGF1, IGF2) as important players in gynecological cancers in
      general, and endometrial tumors in particular. The IGF1 receptor (IGF1R), which
      mediates the proliferative and anti-apoptotic activities of both ligands, emerged
      in recent years as a promising therapeutic target in oncology. However, most
      clinical trials conducted so far led to mixed results, emphasizing the need to
      identify biomarkers that can predict responsiveness to anti-IGF1R-targeted
      therapies. This article will review recent data regarding the role and expression
      of IGF system components in endometrial cancer. In addition, we will review data
      on the interplay between the IGF signaling pathway and tumor suppressors p53 and
      breast cancer susceptibility gene-1 (BRCA1). Anti-oncogenes p53 and BRCA1 play a
      key role in the etiology of gynecological cancers and, therefore, their
      interaction with IGF1R is of high relevance in translational terms. A better
      understanding of the complex mechanisms underlying the regulation of the IGF
      system will improve our ability to develop effective treatment modalities for
      endometrial tumors. 

PMID- 24904529
TI  - Insulin analogs and cancer: a note of caution.
AB  - In view of the lifelong exposure and large patient populations involved, insulin
      analogs with an increased mitogenic effect in comparison to human insulin may
      potentially constitute a major health problem, since these analogs may possibly
      induce the growth of pre-existing neoplasms. At present, the available data
      suggest that insulin analogs are safe. In line with these findings, we observed
      that serum of diabetic patients treated with insulin analogs, compared to that of
      diabetic patients treated with human insulin, did not induce an increased
      phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor
      (IGF-IR). However, the classical model of the IGF-IR signaling may be
      insufficient to explain (all) mitogenic effects of insulin analogs since also non
      canonical signaling pathways of the IGF-IR may play a major role in this respect.
      Although phosphorylation of tyrosine residues of the IGF-IR is generally
      considered to be the initial activation step within the intracellular IGF-IR
      signaling pathway, it has been found that cells undergo a signaling switch under
      hyperglycemic conditions. After this switch, a completely different mechanism is
      utilized to activate the mitogenic (mitogen-activated protein kinase) pathways of
      the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At
      present it is unknown whether activation of this alternative intracellular
      pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is
      stronger in patients treated with (some) insulin analogs than in patients treated
      with human insulin. In addition, it is unknown whether the insulin receptors
      (IRs) also undergo a signaling switch during hyperglycemia. This should be
      investigated in future studies. Finally, relative overexpression of IR isoform A
      (IR-A) in (pre) cancer tissues may play a key role in the development and
      progression of human cancers during treatment with insulin (analogs). Further
      studies are required to unravel whether the IR-A is involved in the development
      of cancers and whether, in this respect (some) insulin analogs differ from human
      insulin. 

PMID- 24904530
TI  - Effects of Estetrol on Migration and Invasion in T47-D Breast Cancer Cells
      through the Actin Cytoskeleton.
AB  - Estetrol (E4) is a natural human estrogen present at high concentrations during
      pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is
      particularly suitable for therapeutic applications. E4 acts as a selective
      estrogen receptor (ER) modulator, exerting estrogenic actions on the endometrium
      or the central nervous system, while antagonizing the actions of estradiol in the
      breast. We tested the effects of E4 on its own or in the presence of 17beta
      estradiol (E2) on T47-D ER+ breast cancer cell migration and invasion of three
      dimensional matrices. E4 administration to T47-D cells weakly stimulated
      migration and invasion. However, E4 decreased the extent of movement and invasion
      induced by E2. Breast cancer cell movement requires a remodeling of the actin
      cytoskeleton. During exposure to E4, a weak, concentration-dependent, re
      distribution of actin fibers toward the cell membrane was observed. However, when
      E4 was added to E2, an inhibition of actin remodeling induced by E2 was seen.
      Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin
      moesin family of actin regulatory proteins, inducing actin and cell membrane
      remodeling. E4 was a weak inducer of moesin phosphorylation on Thr(558), which
      accounts for its functional activation. In co-treatment with E2, E4 blocked the
      activation of this actin controller in a concentration-related fashion. These
      effects were obtained through recruitment of estrogen receptor-alpha. In
      conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton
      remodeling and movement. However, when E2 was present, E4 counteracted the
      stimulatory actions of E2. This contributes to the emerging hypothesis that E4
      may be a naturally occurring ER modulator in the breast. 

PMID- 24904531
TI  - Regulation of Energy Homeostasis by GPR41.
AB  - Imbalances in energy regulation lead to metabolic disorders such as obesity and
      diabetes. Diet plays an essential role in the maintenance of body energy
      homeostasis by acting not only as energy source but also as a signaling modality.
      Excess energy increases energy expenditure, leading to a consumption of it. In
      addition to glucose, mammals utilize short-chain fatty acids (SCFAs), which are
      produced by colonic bacterial fermentation of dietary fiber, as a metabolic fuel.
      The roles of SCFAs in energy regulation have remained unclear, although the roles
      of glucose are well-studied. Recently, a G-protein-coupled receptor deorphanizing
      strategy successfully identified GPR41 (also called free fatty acid receptor 3 or
      FFAR3) as a receptor for SCFAs. GPR41 is expressed in adipose tissue, gut, and
      the peripheral nervous system, and it is involved in SCFA-dependent energy
      regulation. In this mini-review, we focus on the role of GPR41 in host energy
      regulation. 

PMID- 24904532
TI  - Recent progress in research on cell-to-cell movement of rice viruses.
AB  - To adapt to plants as hosts, plant viruses have evolutionally needed the capacity
      to modify the host plasmodesmata (PD) that connect adjacent cells. Plant viruses
      have acquired one or more genes that encode movement proteins (MPs), which
      facilitate the cell-to-cell movement of infectious virus entities through PD to
      adjacent cells. Because of the diversity in their genome organization and in
      their coding sequences, rice viruses may each have a distinct cell-to-cell
      movement strategy. The complexity of their unusual genome organizations and
      replication strategies has so far hampered reverse genetic research on their
      genome in efforts to investigate virally encoded proteins that are involved in
      viral movement. However, the MP of a particular virus can complement defects in
      cell-to-cell movement of other distantly related or even unrelated viruses. Trans
      complementation experiments using a combination of a movement-defective virus and
      viral proteins of interest to identify MPs of several rice viruses have recently
      been successful. In this article, we reviewed recent research that has advanced
      our understanding of cell-to-cell movement of rice viruses. 

PMID- 24904533
TI  - Calcifying nanoparticles: one face of distinct entities?

PMID- 24904535
TI  - Deciphering microbial interactions and detecting keystone species with co
      occurrence networks.
AB  - Co-occurrence networks produced from microbial survey sequencing data are
      frequently used to identify interactions between community members. While this
      approach has potential to reveal ecological processes, it has been insufficiently
      validated due to the technical limitations inherent in studying complex microbial
      ecosystems. Here, we simulate multi-species microbial communities with known
      interaction patterns using generalized Lotka-Volterra dynamics. We then construct
      co-occurrence networks and evaluate how well networks reveal the underlying
      interactions and how experimental and ecological parameters can affect network
      inference and interpretation. We find that co-occurrence networks can
      recapitulate interaction networks under certain conditions, but that they lose
      interpretability when the effects of habitat filtering become significant. We
      demonstrate that networks suffer from local hot spots of spurious correlation in
      the neighborhood of hub species that engage in many interactions. We also
      identify topological features associated with keystone species in co-occurrence
      networks. This study provides a substantiated framework to guide environmental
      microbiologists in the construction and interpretation of co-occurrence networks
      from microbial survey datasets. 

PMID- 24904536
TI  - Lipid domains in HIV-1 assembly.
AB  - In CD(+) 4 T cells, HIV-1 buds from the host cell plasma membrane. The viral Gag
      polyprotein is mainly responsible for this process. However, the intimate
      interaction of Gag and lipids at the plasma membrane as well as its consequences,
      in terms of lipids lateral organization and virus assembly, is still under
      debate. In this review we propose to revisit the role of plasma membrane lipids
      in HIV-1 Gag targeting and assembly, at the light of lipid membranes biophysics
      and literature dealing with Gag-lipid interactions. 

PMID- 24904534
TI  - Functional annotation of human cytomegalovirus gene products: an update.
AB  - Human cytomegalovirus is an opportunistic double-stranded DNA virus with one of
      the largest viral genomes known. The 235 kB genome is divided in a unique long
      (UL) and a unique short (US) region which are flanked by terminal and internal
      repeats. The expression of HCMV genes is highly complex and involves the
      production of protein coding transcripts, polyadenylated long non-coding RNAs,
      polyadenylated anti-sense transcripts and a variety of non-polyadenylated RNAs
      such as microRNAs. Although the function of many of these transcripts is unknown,
      they are suggested to play a direct or regulatory role in the delicately
      orchestrated processes that ensure HCMV replication and life-long persistence.
      This review focuses on annotating the complete viral genome based on three
      sources of information. First, previous reviews were used as a template for the
      functional keywords to ensure continuity; second, the Uniprot database was used
      to further enrich the functional database; and finally, the literature was
      manually curated for novel functions of HCMV gene products. Novel discoveries
      were discussed in light of the viral life cycle. This functional annotation
      highlights still poorly understood regions of the genome but more importantly it
      can give insight in functional clusters and/or may be helpful in the analysis of
      future transcriptomics and proteomics studies. 

PMID- 24904538
TI  - Characterizing the avian gut microbiota: membership, driving influences, and
      potential function.
AB  - Birds represent a diverse and evolutionarily successful lineage, occupying a wide
      range of niches throughout the world. Like all vertebrates, avians harbor diverse
      communities of microorganisms within their guts, which collectively fulfill
      important roles in providing the host with nutrition and protection from
      pathogens. Although many studies have investigated the role of particular
      microbes in the guts of avian species, there has been no attempt to unify the
      results of previous, sequence-based studies to examine the factors that shape the
      avian gut microbiota as a whole. In this study, we present the first meta
      analysis of the avian gut microbiota, using 16S rRNA gene sequences obtained from
      a range of publicly available clone-library and amplicon pyrosequencing data. We
      investigate community membership and structure, as well as probe the roles of
      some of the key biological factors that influence the gut microbiota of other
      vertebrates, such as host phylogeny, location within the gut, diet, and
      association with humans. Our results indicate that, across avian studies, the
      microbiota demonstrates a similar phylum-level composition to that of mammals.
      Host bird species is the most important factor in determining community
      composition, although sampling site, diet, and captivity status also contribute.
      These analyses provide a first integrated look at the composition of the avian
      microbiota, and serve as a foundation for future studies in this area. 

PMID- 24904537
TI  - A new paradigm: innate immune sensing of viruses via the unfolded protein
      response.
AB  - THE IMMUNE SYSTEM DEPENDS UPON COMBINATIONS OF SIGNALS TO MOUNT APPROPRIATE
      RESPONSES: pathogen specific signals in the context of co-stimulatory "danger"
      signals drive immune strength and accuracy. Viral infections trigger anti-viral
      type I interferon (IFN) responses by stimulating endosomal and cytosolic pattern
      recognition receptors (PRRs). However, viruses have also evolved many strategies
      to counteract IFN responses. Are there intracellular danger signals that enhance
      immune responses to viruses? During infection, viruses place a heavy demand on
      the protein folding machinery of the host endoplasmic reticulum (ER). To survive
      ER stress, host cells mount an unfolded protein response (UPR) to decrease ER
      protein load and enhance protein-folding capacity. Viruses also directly elicit
      the UPR to enhance their replication. Increasing evidence supports an
      intersection between the host UPR and inflammation, in particular the production
      of pro-inflammatory cytokines and type I IFN. The UPR directly activates pro
      inflammatory cytokine transcription factors and dramatically enhances cytokine
      production in response to viral PRR engagement. Additionally, viral PRR
      engagement may stimulate specific pathways within the UPR to enhance cytokine
      production. Through these mechanisms, viral detection via the UPR and
      inflammatory cytokine production are intertwined. Consequently, the UPR response
      is perfectly poised to act as an infection-triggered "danger" signal. The UPR may
      serve as an internal "co-stimulatory" signal that (1) provides specificity and
      (2) critically augments responses to overcome viral subterfuge. Further work is
      needed to test this hypothesis during viral infections. 

PMID- 24904539
TI  - DNA polymerase hybrids derived from the family-B enzymes of Pyrococcus furiosus
      and Thermococcus kodakarensis: improving performance in the polymerase chain
      reaction.
AB  - The polymerase chain reaction (PCR) is widely applied across the biosciences,
      with archaeal Family-B DNA polymerases being preferred, due to their high
      thermostability and fidelity. The enzyme from Pyrococcus furiosus (Pfu-Pol) is
      more frequently used than the similar protein from Thermococcus kodakarensis
      (Tkod-Pol), despite the latter having better PCR performance. Here the two
      polymerases have been comprehensively compared, confirming that Tkod-Pol: (1)
      extends primer-templates more rapidly; (2) has higher processivity; (3)
      demonstrates superior performance in normal and real time PCR. However, Tkod-Pol
      is less thermostable than Pfu-Pol and both enzymes have equal fidelities. To
      understand the favorable properties of Tkod-Pol, hybrid proteins have been
      prepared. Single, double and triple mutations were used to site arginines,
      present at the "forked-point" (the junction of the exonuclease and polymerase
      channels) of Tkod-Pol, at the corresponding locations in Pfu-Pol, slightly
      improving PCR performance. The Pfu-Pol thumb domain, responsible for double
      stranded DNA binding, has been entirely replaced with that from Tkod-Pol, again
      giving better PCR properties. Combining the "forked-point" and thumb swap
      mutations resulted in a marked increase in PCR capability, maintenance of high
      fidelity and retention of the superior thermostability associated with Pfu-Pol.
      However, even the arginine/thumb swap mutant falls short of Tkod-Pol in PCR,
      suggesting further improvement within the Pfu-Pol framework is attainable. The
      significance of this work is the observation that improvements in PCR performance
      are easily attainable by blending elements from closely related archaeal
      polymerases, an approach that may, in future, be extended by using more
      polymerases from these organisms. 

PMID- 24904540
TI  - Thaumarchaeal ammonium oxidation and evidence for a nitrogen cycle in a
      subsurface radioactive thermal spring in the Austrian Central Alps.
AB  - Previous studies had suggested the presence of ammonium oxidizing Thaumarchaeota
      as well as nitrite oxidizing Bacteria in the subsurface spring called Franz Josef
      Quelle (FJQ), a slightly radioactive thermal mineral spring with a temperature of
      43.6-47 degrees C near the alpine village of Bad Gastein, Austria. The
      microbiological consortium of the FJQ was investigated for its utilization of
      nitrogen compounds and the putative presence of a subsurface nitrogen cycle.
      Microcosm experiments made with samples from the spring water, containing
      planktonic microorganisms, or from biofilms, were used in this study. Three
      slightly different media, enriched with vitamins and trace elements, and two
      incubation temperatures (30 and 40 degrees C, respectively) were employed. Under
      aerobic conditions, high rates of conversion of ammonium to nitrite, as well as
      nitrite to nitrate were measured. Under oxygen-limited conditions nitrate was
      converted to gaseous compounds. Stable isotope probing with (15)NH4Cl or
      ((15)NH4)2SO4as sole energy sources revealed incorporation of (15)N into
      community DNA. Genomic DNA as well as RNA were extracted from all microcosms. The
      following genes or fragments of genes were successfully amplified, cloned and
      sequenced by standard PCR from DNA extracts: Ammonia monooxygenase subunit A
      (amoA), nitrite oxidoreductase subunits A and B (nxrA and nxrB), nitrate
      reductase (narG), nitrite reductase (nirS), nitric oxide reductases (cnorB and
      qnorB), nitrous oxide reductase (nosZ). Reverse transcription of extracted total
      RNA and real-time PCR suggested the expression of each of those genes. Nitrogen
      fixation (as probed with nifH and nifD) was not detected. However, a geological
      origin of NH(+) 4 in the water of the FJQ cannot be excluded, considering the
      silicate, granite and gneiss containing environment. The data suggested the
      operation of a nitrogen cycle in the subsurface environment of the FJQ. 

PMID- 24904542
TI  - Antibacterial activity of silver nanoparticles: sensitivity of different
      Salmonella serovars.
AB  - Salmonella spp. is one of the main causes of foodborne illnesses in humans
      worldwide. Consequently, great interest exists in reducing its impact on human
      health by lowering its prevalence in the food chain. Antimicrobial formulations
      in the form of nanoparticles exert bactericidal action due to their enhanced
      reactivity resultant from their high surface/volume ratio. Silver nanoparticles
      (AgNPs) are known to be highly toxic to Gram-negative and Gram-positive
      microorganisms, including multidrug resistant bacteria. However, few data
      concerning their success against different Salmonella serovars are available.
      Aims of the present study were to test the antimicrobial effectiveness of AgNPs,
      against Salmonella Enteritidis, Hadar, and Senftenberg, and to investigate the
      causes of their different survival abilities from a molecular point of view.
      Results showed an immediate, time-limited and serovar-dependent reduction of
      bacterial viability. In the case of S. Senftenberg, the reduction in numbers was
      observed for up to 4 h of incubation in the presence of 200 mg/l of AgNPs; on the
      contrary, S. Enteritidis and S. Hadar resulted to be inhibited for up to 48 h.
      Reverse transcription and polymerase chain reaction experiments demonstrated the
      constitutive expression of the plasmidic silver resistance determinant (SilB) by
      S. Senftenberg, thus suggesting the importance of a cautious use of AgNPs. 

PMID- 24904543
TI  - Parasitic chytrids sustain zooplankton growth during inedible algal bloom.
AB  - This study assesses the quantitative impact of parasitic chytrids on the
      planktonic food web of two contrasting freshwater lakes during different algal
      bloom situations. Carbon-based food web models were used to investigate the
      effects of chytrids during the spring diatom bloom in Lake Pavin (oligo
      mesotrophic) and the autumn cyanobacteria bloom in Lake Aydat (eutrophic). Linear
      inverse modeling was employed to estimate undetermined flows in both lakes. The
      Monte Carlo Markov chain linear inverse modeling procedure provided estimates of
      the ranges of model-derived fluxes. Model results confirm recent theories on the
      impact of parasites on food web function through grazers and recyclers. During
      blooms of "inedible" algae (unexploited by planktonic herbivores), the epidemic
      growth of chytrids channeled 19-20% of the primary production in both lakes
      through the production of grazer exploitable zoospores. The parasitic throughput
      represented 50% and 57% of the zooplankton diet, respectively, in the oligo
      mesotrophic and in the eutrophic lakes. Parasites also affected ecological
      network properties such as longer carbon path lengths and loop strength, and
      contributed to increase the stability of the aquatic food web, notably in the
      oligo-mesotrophic Lake Pavin. 

PMID- 24904541
TI  - Epidemiology of virus-induced asthma exacerbations: with special reference to the
      role of human rhinovirus.
AB  - Viral respiratory infections may be associated with the virus-induced asthma in
      adults as well as children. Particularly, human rhinovirus is strongly suggested
      a major candidate for the associations of the virus-induced asthma. Thus, in this
      review, we reviewed and focused on the epidemiology, pathophysiology, and
      treatment of virus-induced asthma with special reference on human rhinovirus.
      Furthermore, we added our preliminary data regarding the clinical and virological
      findings in the present review. 

PMID- 24904544
TI  - Loss of diversity in wood-inhabiting fungal communities affects decomposition
      activity in Norway spruce wood.
AB  - Hundreds of wood-inhabiting fungal species are now threatened, principally due to
      a lack of dead wood in intensively managed forests, but the consequences of
      reduced fungal diversity on ecosystem functioning are not known. Several
      experiments have shown that primary productivity is negatively affected by a loss
      of species, but the effects of microbial diversity on decomposition are less
      studied. We studied the relationship between fungal diversity and the in vitro
      decomposition rate of slightly, moderately and heavily decayed Picea abies wood
      with indigenous fungal communities that were diluted to examine the influence of
      diversity. Respiration rate, wood-degrading hydrolytic enzymes and fungal
      community structure were assessed during a 16-week incubation. The number of
      observed OTUs in DGGE was used as a measure of fungal diversity. Respiration rate
      increased between early- and late-decay stages. Reduced fungal diversity was
      associated with lower respiration rates during intermediate stages of decay, but
      no effects were detected at later stages. The activity of hydrolytic enzymes
      varied among decay stages and fungal dilutions. Our results suggest that
      functioning of highly diverse communities of the late-decay stage were more
      resistant to the loss of diversity than less diverse communities of early
      decomposers. This indicates the accumulation of functional redundancy during the
      succession of the fungal community in decomposing substrates. 

PMID- 24904545
TI  - Recoding of the stop codon UGA to glycine by a BD1-5/SN-2 bacterium and niche
      partitioning between Alpha- and Gammaproteobacteria in a tidal sediment microbial
      community naturally selected in a laboratory chemostat.
AB  - Sandy coastal sediments are global hotspots for microbial mineralization of
      organic matter and denitrification. These sediments are characterized by
      advective porewater flow, tidal cycling and an active and complex microbial
      community. Metagenomic sequencing of microbial communities sampled from such
      sediments showed that potential sulfur oxidizing Gammaproteobacteria and members
      of the enigmatic BD1-5/SN-2 candidate phylum were abundant in situ (>10% and ~2%
      respectively). By mimicking the dynamic oxic/anoxic environmental conditions of
      the sediment in a laboratory chemostat, a simplified microbial community was
      selected from the more complex inoculum. Metagenomics, proteomics and
      fluorescence in situ hybridization showed that this simplified community
      contained both a potential sulfur oxidizing Gammaproteobacteria (at 24 +/- 2%
      abundance) and a member of the BD1-5/SN-2 candidate phylum (at 7 +/- 6%
      abundance). Despite the abundant supply of organic substrates to the chemostat,
      proteomic analysis suggested that the selected gammaproteobacterium grew
      partially autotrophically and performed hydrogen/formate oxidation. The
      enrichment of a member of the BD1-5/SN-2 candidate phylum enabled, for the first
      time, direct microscopic observation by fluorescent in situ hybridization and the
      experimental validation of the previously predicted translation of the stop codon
      UGA into glycine. 

PMID- 24904546
TI  - The activity of Nef on HIV-1 infectivity.
AB  - The replication and pathogenicity of lentiviruses is crucially modulated by
      "auxiliary proteins" which are expressed in addition to the canonical retroviral
      ORFs gag, pol, and env. Strategies to inhibit the activity of such proteins are
      often sought and proposed as possible additions to increase efficacy of the
      traditional antiretroviral therapy. This requires the acquisition of an in-depth
      knowledge of the molecular mechanisms underlying their function. The Nef
      auxiliary protein is expressed uniquely by primate lentiviruses and plays an
      important role in virus replication in vivo and in the onset of AIDS. Among its
      several activities Nef enhances the intrinsic infectivity of progeny virions
      through a mechanism which remains today enigmatic. Here we review the current
      knowledge surrounding such activity and we discuss its possible role in HIV
      biology. 

PMID- 24904548
TI  - Tsg101 regulates PI(4,5)P2/Ca(2+) signaling for HIV-1 Gag assembly.
AB  - Our previous studies identified the 1,4,5-inositol trisphosphate receptor (IP3R),
      a channel mediating release of Ca(2+) from ER stores, as a cellular factor
      differentially associated with HIV-1 Gag that might facilitate ESCRT function in
      virus budding. Channel opening requires activation that is initiated by binding
      of 1,4,5-triphosphate (IP3), a product of phospholipase C (PLC)-mediated
      PI(4,5)P2 hydrolysis. The store emptying that follows stimulates store refilling
      which requires intact PI(4,5)P2. Raising cytosolic Ca(2+) promotes viral particle
      production and our studies indicate that IP3R and the ER Ca(2+) store are the
      physiological providers of Ca(2+) for Gag assembly and release. Here, we show
      that Gag modulates ER store gating and refilling. Cells expressing Gag exhibited
      a higher cytosolic Ca(2+) level originating from the ER store than control cells,
      suggesting that Gag induced release of store Ca(2+). This property required the
      PTAP motif in Gag that recruits Tsg101, an ESCRT-1 component. Consistent with
      cytosolic Ca(2+) elevation, Gag accumulation at the plasma membrane was found to
      require continuous IP3R activation. Like other IP3R channel modulators, Gag was
      detected in physical proximity to the ER and to endogenous IP3R, as indicated
      respectively by total internal reflection fluorescence (TIRF) and immunoelectron
      microscopy (IEM) or indirect immunofluorescence. Reciprocal co
      immunoprecipitation suggested that Gag and IP3R proximity is favored when the
      PTAP motif in Gag is intact. Gag expression was also accompanied by increased
      PI(4,5)P2 accumulation at the plasma membrane, a condition favoring store
      refilling capacity. Supporting this notion, Gag particle production was
      impervious to treatment with 2-aminoethoxydiphenyl borate, an inhibitor of a
      refilling coupling interaction. In contrast, particle production by a Gag mutant
      lacking the PTAP motif was reduced. We conclude that a functional PTAP L domain,
      and by inference Tsg101 binding, confers Gag with an ability to modulate both ER
      store Ca(2+) release and ER store refilling. 

PMID- 24904550
TI  - Interactions of the cell-wall glycopolymers of lactic acid bacteria with their
      bacteriophages.
AB  - Lactic acid bacteria (LAB) are Gram positive bacteria widely used in the
      production of fermented food in particular cheese and yoghurts. Bacteriophage
      infections during fermentation processes have been for many years a major
      industrial concern and have stimulated numerous research efforts. Better
      understanding of the molecular mechanisms of bacteriophage interactions with
      their host bacteria is required for the development of efficient strategies to
      fight against infections. The bacterial cell wall plays key roles in these
      interactions. First, bacteriophages must adsorb at the bacterial surface through
      specific interactions with receptors that are cell wall components. At next step,
      phages must overcome the barrier constituted by cell wall peptidoglycan (PG) to
      inject DNA inside bacterial cell. Also at the end of the infection cycle, phages
      synthesize endolysins able to hydrolyze PG and lyse bacterial cells to release
      phage progeny. In the last decade, concomitant development of genomics and
      structural analysis of cell wall components allowed considerable advances in the
      knowledge of their structure and function in several model LAB. Here, we describe
      the present knowledge on the structure of the cell wall glycopolymers of the best
      characterized LAB emphasizing their structural variations and we present the
      available data regarding their role in bacteria-phage specific interactions at
      the different steps of the infection cycle. 

PMID- 24904552
TI  - Short-sighted evolution of bacterial opportunistic pathogens with an
      environmental origin.

PMID- 24904547
TI  - Unfolded protein response in hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of
      clinical importance. The virus establishes a chronic infection and can progress
      from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular
      carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly
      understood. Recently the unfolded protein response (UPR), a cellular homeostatic
      response to endoplasmic reticulum (ER) stress, has emerged to be a major
      contributing factor in many human diseases. It is also evident that viruses
      interact with the host UPR in many different ways and the outcome could be pro
      viral, anti-viral or pathogenic, depending on the particular type of infection.
      Here we present evidence for the elicitation of chronic ER stress in HCV
      infection. We analyze the UPR signaling pathways involved in HCV infection, the
      various levels of UPR regulation by different viral proteins and finally, we
      propose several mechanisms by which the virus provokes the UPR. 

PMID- 24904551
TI  - Plugging in or going wireless: strategies for interspecies electron transfer.
AB  - Interspecies exchange of electrons enables a diversity of microbial communities
      to gain energy from reactions that no one microbe can catalyze. The first
      recognized strategies for interspecies electron transfer were those that relied
      on chemical intermediates that are recycled through oxidized and reduced forms.
      Well-studied examples are interspecies H2 transfer and the cycling of sulfur
      intermediates in anaerobic photosynthetic communities. Direct interspecies
      electron transfer (DIET) in which two species establish electrical contact is an
      alternative. Electrical contacts documented to date include electrically
      conductive pili, as well as conductive iron minerals and conductive carbon
      moieties such as activated carbon and biochar. Interspecies electron transfer is
      central to the functioning of methane-producing microbial communities. The
      importance of interspecies H2 transfer in many methanogenic communities is clear,
      but under some circumstances DIET predominates. It is expected that further
      mechanistic studies and broadening investigations to a wider range of
      environments will help elucidate the factors that favor specific forms of
      interspecies electron exchange under different environmental conditions. 

PMID- 24904553
TI  - Potential role of bacteria packaging by protozoa in the persistence and
      transmission of pathogenic bacteria.
AB  - Many pathogenic bacteria live in close association with protozoa. These
      unicellular eukaryotic microorganisms are ubiquitous in various environments. A
      number of protozoa such as amoebae and ciliates ingest pathogenic bacteria,
      package them usually in membrane structures, and then release them into the
      environment. Packaged bacteria are more resistant to various stresses and are
      more apt to survive than free bacteria. New evidence indicates that protozoa and
      not bacteria control the packaging process. It is possible that packaging is more
      common than suspected and may play a major role in the persistence and
      transmission of pathogenic bacteria. To confirm the role of packaging in the
      propagation of infections, it is vital that the molecular mechanisms governing
      the packaging of bacteria by protozoa be identified as well as elements related
      to the ecology of this process in order to determine whether packaging acts as a
      Trojan Horse. 

PMID- 24904556
TI  - Microbial acetone oxidation in coastal seawater.
AB  - Acetone is an important oxygenated volatile organic compound (OVOC) in the
      troposphere where it influences the oxidizing capacity of the atmosphere.
      However, the air-sea flux is not well quantified, in part due to a lack of
      knowledge regarding which processes control oceanic concentrations, and,
      specifically whether microbial oxidation to CO2 represents a significant loss
      process. We demonstrate that (14)C labeled acetone can be used to determine
      microbial oxidation to (14)CO2. Linear microbial rates of acetone oxidation to
      CO2 were observed for between 0.75-3.5 h at a seasonally eutrophic coastal
      station located in the western English Channel (L4). A kinetic experiment in
      summer at station L4 gave a V max of 4.1 pmol L(-1) h(-1), with a K m constant of
      54 pM. We then used this technique to obtain microbial acetone loss rates ranging
      between 1.2 and 42 pmol L(-1) h(-1.)(monthly averages) over an annual cycle at
      L4, with maximum rates observed during winter months. The biological turnover
      time of acetone (in situ concentration divided by microbial oxidation rate) in
      surface waters varied from ~3 days in February 2011, when in situ concentrations
      were 3 +/- 1 nM, to >240 days in June 2011, when concentrations were more than
      twofold higher at 7.5 +/- 0.7 nM. These relatively low marine microbial acetone
      oxidation rates, when normalized to in situ concentrations, suggest that marine
      microbes preferentially utilize other OVOCs such as methanol and acetaldehyde. 

PMID- 24904555
TI  - Unexplored hypersaline habitats are sources of novel actinomycetes.

PMID- 24904554
TI  - Antibacterial activities of bacteriocins: application in foods and
      pharmaceuticals.
AB  - Bacteriocins are a kind of ribosomal synthesized antimicrobial peptides produced
      by bacteria, which can kill or inhibit bacterial strains closely-related or non
      related to produced bacteria, but will not harm the bacteria themselves by
      specific immunity proteins. Bacteriocins become one of the weapons against
      microorganisms due to the specific characteristics of large diversity of
      structure and function, natural resource, and being stable to heat. Many recent
      studies have purified and identified bacteriocins for application in food
      technology, which aims to extend food preservation time, treat pathogen disease
      and cancer therapy, and maintain human health. Therefore, bacteriocins may become
      a potential drug candidate for replacing antibiotics in order to treat multiple
      drugs resistance pathogens in the future. This review article summarizes
      different types of bacteriocins from bacteria. The latter half of this review
      focuses on the potential applications in food science and pharmaceutical
      industry. 

PMID- 24904557
TI  - Ecological functions of zoosporic hyperparasites.
AB  - Zoosporic parasites have received increased attention during the last years, but
      it is still largely unnoted that these parasites can themselves be infected by
      hyperparasites. Some members of the Chytridiomycota, Blastocladiomycota,
      Cryptomycota, Hyphochytriomycota, Labyrinthulomycota, Oomycota, and Phytomyxea
      are hyperparasites of zoosporic hosts. Because of sometimes complex tripartite
      interactions between hyperparasite, their parasite-host, and the primary host,
      hyperparasites can be difficult to detect and monitor. Some of these
      hyperparasites use similar mechanisms as their parasite-hosts to find and infect
      their target and to access food resources. The life cycle of zoosporic
      hyperparasites is usually shorter than the life cycle of their hosts, so
      hyperparasites may accelerate the turnaround times of nutrients within the
      ecosystem. Hyperparasites may increase the complexity of food webs and play
      significant roles in regulating population sizes and population dynamics of their
      hosts. We suggest that hyperparasites lengthen food chains but can also play a
      role in conducting or suppressing diseases of animals, plants, or algae.
      Hyperparasites can significantly impact ecosystems in various ways, therefore it
      is important to increase our understanding about these cryptic and diverse
      organisms. 

PMID- 24904558
TI  - Identification of genes specifically required for the anaerobic metabolism of
      benzene in Geobacter metallireducens.
AB  - Although the biochemical pathways for the anaerobic degradation of many of the
      hydrocarbon constituents in petroleum reservoirs have been elucidated, the
      mechanisms for anaerobic activation of benzene, a very stable molecule, are not
      known. Previous studies have demonstrated that Geobacter metallireducens can
      anaerobically oxidize benzene to carbon dioxide with Fe(III) as the sole electron
      acceptor and that phenol is an intermediate in benzene oxidation. In an attempt
      to identify enzymes that might be involved in the conversion of benzene to
      phenol, whole-genome gene transcript abundance was compared in cells metabolizing
      benzene and cells metabolizing phenol. Eleven genes had significantly higher
      transcript abundance in benzene-metabolizing cells. Five of these genes had
      annotations suggesting that they did not encode proteins that could be involved
      in benzene metabolism and were not further studied. Strains were constructed in
      which one of the remaining six genes was deleted. The strain in which the
      monocistronic gene Gmet 0232 was deleted metabolized phenol, but not benzene.
      Transcript abundance of the adjacent monocistronic gene, Gmet 0231, predicted to
      encode a zinc-containing oxidoreductase, was elevated in cells metabolizing
      benzene, although not at a statistically significant level. However, deleting
      Gmet 0231 also yielded a strain that could metabolize phenol, but not benzene.
      Although homologs of Gmet 0231 and Gmet 0232 are found in microorganisms not
      known to anaerobically metabolize benzene, the adjacent localization of these
      genes is unique to G. metallireducens. The discovery of genes that are
      specifically required for the metabolism of benzene, but not phenol in G.
      metallireducens is an important step in potentially identifying the mechanisms
      for anaerobic benzene activation. 

PMID- 24904559
TI  - Elucidation of Zymomonas mobilis physiology and stress responses by quantitative
      proteomics and transcriptomics.
AB  - Zymomonas mobilis is an excellent ethanologenic bacterium. Biomass pretreatment
      and saccharification provides access to simple sugars, but also produces
      inhibitors such as acetate and furfural. Our previous work has identified and
      confirmed the genetic change of a 1.5-kb deletion in the sodium acetate tolerant
      Z. mobilis mutant (AcR) leading to constitutively elevated expression of a sodium
      proton antiporter encoding gene nhaA, which contributes to the sodium acetate
      tolerance of AcR mutant. In this study, we further investigated the responses of
      AcR and wild-type ZM4 to sodium acetate stress in minimum media using both
      transcriptomics and a metabolic labeling approach for quantitative proteomics the
      first time. Proteomic measurements at two time points identified about eight
      hundreds proteins, or about half of the predicted proteome. Extracellular
      metabolite analysis indicated AcR overcame the acetate stress quicker than ZM4
      with a concomitant earlier ethanol production in AcR mutant, although the final
      ethanol yields and cell densities were similar between two strains.
      Transcriptomic samples were analyzed for four time points and revealed that the
      response of Z. mobilis to sodium acetate stress is dynamic, complex, and involved
      about one-fifth of the total predicted genes from all different functional
      categories. The modest correlations between proteomic and transcriptomic data may
      suggest the involvement of posttranscriptional control. In addition, the
      transcriptomic data of forty-four microarrays from four experiments for ZM4 and
      AcR under different conditions were combined to identify strain-specific, media
      responsive, growth phase-dependent, and treatment-responsive gene expression
      profiles. Together this study indicates that minimal medium has the most dramatic
      effect on gene expression compared to rich medium followed by growth phase,
      inhibitor, and strain background. Genes involved in protein biosynthesis,
      glycolysis and fermentation as well as ATP synthesis and stress response play key
      roles in Z. mobilis metabolism with consistently strong expression levels under
      different conditions. 

PMID- 24904560
TI  - Connecting lignin-degradation pathway with pre-treatment inhibitor sensitivity of
      Cupriavidus necator.
AB  - To produce lignocellulosic biofuels economically, the complete release of
      monomers from the plant cell wall components, cellulose, hemicellulose, and
      lignin, through pre-treatment and hydrolysis (both enzymatic and chemical), and
      the efficient utilization of these monomers as carbon sources, is crucial. In
      addition, the identification and development of robust microbial biofuel
      production strains that can tolerate the toxic compounds generated during pre
      treatment and hydrolysis is also essential. In this work, Cupriavidus necator was
      selected due to its capabilities for utilizing lignin monomers and producing
      polyhydroxylbutyrate (PHB), a bioplastic as well as an advanced biofuel
      intermediate. We characterized the growth kinetics of C. necator in pre-treated
      corn stover slurry as well as individually in the pre-sence of 11 potentially
      toxic compounds in the saccharified slurry. We found that C. necator was
      sensitive to the saccharified slurry produced from dilute acid pre-treated corn
      stover. Five out of 11 compounds within the slurry were characterized as toxic to
      C. necator, namely ammonium acetate, furfural, hydroxymethylfurfural (HMF),
      benzoic acid, and p-coumaric acid. Aldehydes (e.g., furfural and HMF) were more
      toxic than the acetate and the lignin degradation products benzoic acid and p
      coumaric acid; furfural was identified as the most toxic compound. Although toxic
      to C. necator at high concentration, ammonium acetate, benzoic acid, and p
      coumaric acid could be utilized by C. necator with a stimulating effect on C.
      necator growth. Consequently, the lignin degradation pathway of C. necator was
      reconstructed based on genomic information and literature. The efficient
      conversion of intermediate catechol to downstream products of cis,cis-muconate or
      2-hydroxymuconate-6-semialdehyde may help improve the robustness of C. necator to
      benzoic acid and p-coumaric acid as well as improve PHB productivity. 

PMID- 24904561
TI  - Malaria drives T cells to exhaustion.
AB  - Malaria is a significant global burden but after >30 years of effort there is no
      vaccine on the market. While the complex life cycle of the parasite presents
      several challenges, many years of research have also identified several
      mechanisms of immune evasion by Plasmodium spp. Recent research on malaria, has
      investigated the programmed cell death-1 (PD-1) pathway which mediates exhaustion
      of T cells, characterized by poor effector functions and recall responses and in
      some cases loss of the cells by apoptosis. Such studies have shown exhaustion of
      CD4(+) T cells and an unappreciated role for CD8(+) T cells in promoting sterile
      immunity against blood stage malaria. This is because PD-1 mediates up to a 95%
      reduction in numbers and functional capacity of parasite-specific CD8(+) T cells,
      thus masking their role in protection. The role of T cell exhaustion during
      malaria provides an explanation for the absence of sterile immunity following the
      clearance of acute disease which will be relevant to future malaria-vaccine
      design and suggests the need for novel therapeutic solutions. This review will
      thus examine the role of PD-1-mediated T cell exhaustion in preventing lasting
      immunity against malaria. 

PMID- 24904564
TI  - Effect of the strain Bacillus amyloliquefaciens FZB42 on the microbial community
      in the rhizosphere of lettuce under field conditions analyzed by whole metagenome
      sequencing.
AB  - Application of the plant associated bacterium Bacillus amyloliquefaciens FZB42 on
      lettuce (Lactuca sativa) confirmed its capability to promote plant growth and
      health by reducing disease severity (DS) caused by the phytopathogenic fungus
      Rhizoctonia solani. Therefore this strain is commercially applied as an eco
      friendly plant protective agent. It is able to produce cyclic lipopeptides (CLP)
      and polyketides featuring antifungal and antibacterial properties. Production of
      these secondary metabolites led to the question of a possible impact of strain
      FZB42 on the composition of microbial rhizosphere communities after its
      application. Rating of DS and lettuce growth during a field trial confirmed the
      positive impact of strain FZB42 on the health of the host plant. To verify B.
      amyloliquefaciens as an environmentally compatible plant protective agent, its
      effect on the indigenous rhizosphere community was analyzed by metagenome
      sequencing. Rhizosphere microbial communities of lettuce treated with B.
      amyloliquefaciens FZB42 and non-treated plants were profiled by high-throughput
      metagenome sequencing of whole community DNA. Fragment recruitments of metagenome
      sequence reads on the genome sequence of B. amyloliquefaciens FZB42 proved the
      presence of the strain in the rhizosphere over 5 weeks of the field trial.
      Comparison of taxonomic community profiles only revealed marginal changes after
      application of strain FZB42. The orders Burkholderiales, Actinomycetales and
      Rhizobiales were most abundant in all samples. Depending on plant age a general
      shift within the composition of the microbial communities that was independent of
      the application of strain FZB42 was observed. In addition to the taxonomic
      profiling, functional analysis of annotated sequences revealed no major
      differences between samples regarding application of the inoculant strain. 

PMID- 24904563
TI  - Trait-based approaches for understanding microbial biodiversity and ecosystem
      functioning.
AB  - In ecology, biodiversity-ecosystem functioning (BEF) research has seen a shift in
      perspective from taxonomy to function in the last two decades, with successful
      application of trait-based approaches. This shift offers opportunities for a
      deeper mechanistic understanding of the role of biodiversity in maintaining
      multiple ecosystem processes and services. In this paper, we highlight studies
      that have focused on BEF of microbial communities with an emphasis on integrating
      trait-based approaches to microbial ecology. In doing so, we explore some of the
      inherent challenges and opportunities of understanding BEF using microbial
      systems. For example, microbial biologists characterize communities using gene
      phylogenies that are often unable to resolve functional traits. Additionally,
      experimental designs of existing microbial BEF studies are often inadequate to
      unravel BEF relationships. We argue that combining eco-physiological studies with
      contemporary molecular tools in a trait-based framework can reinforce our ability
      to link microbial diversity to ecosystem processes. We conclude that such trait
      based approaches are a promising framework to increase the understanding of
      microbial BEF relationships and thus generating systematic principles in
      microbial ecology and more generally ecology. 

PMID- 24904565
TI  - Identification of overexpressed genes in Sodalis glossinidius inhabiting
      trypanosome-infected self-cured tsetse flies.
AB  - Sodalis glossinidius, one of the three tsetse fly maternally inherited symbionts,
      was previously shown to favor fly infection by trypanosomes, the parasites
      causing human sleeping sickness. Among a population of flies taking a trypanosome
      infected blood meal, only a few individuals will acquire the parasite; the others
      will escape infection and be considered as refractory to trypanosome infection.
      The aim of the work was to investigate whether fly refractoriness could be
      associated with specific Sodalis gene expression. The transcriptome of S.
      glossinidius harbored by flies that were fed either with a non-infected blood
      meal (control) or with a trypanosome-infected meal but that did not develop
      infection were analyzed, using microarray technology, and compared. The analysis
      using the microarray procedure yielded 17 genes that were found to have a
      significant differential expression between the two groups. Interestingly, all
      these genes were overexpressed in self-cured (refractory) flies. Further analysis
      of functional annotation of these genes indicated that most associated biological
      process terms were related to metabolic and biosynthetic processes as well as to
      oxido-reduction mechanisms. These results evidence the occurrence of molecular
      crosstalk between the different partners, induced by the passage of the
      trypanosomes through the fly's gut even though the parasites were unable to
      establish in the gut and to develop a permanent infection. 

PMID- 24904562
TI  - Cellular unfolded protein response against viruses used in gene therapy.
AB  - Viruses are excellent vehicles for gene therapy due to their natural ability to
      infect and deliver the cargo to specific tissues with high efficiency. Although
      such vectors are usually "gutted" and are replication defective, they are
      subjected to clearance by the host cells by immune recognition and destruction.
      Unfolded protein response (UPR) is a naturally evolved cyto-protective signaling
      pathway which is triggered due to endoplasmic reticulum (ER) stress caused by
      accumulation of unfolded/misfolded proteins in its lumen. The UPR signaling
      consists of three signaling pathways, namely PKR-like ER kinase, activating
      transcription factor 6, and inositol-requiring protein-1. Once activated, UPR
      triggers the production of ER molecular chaperones and stress response proteins
      to help reduce the protein load within the ER. This occurs by degradation of the
      misfolded proteins and ensues in the arrest of protein translation machinery. If
      the burden of protein load in ER is beyond its processing capacity, UPR can
      activate pro-apoptotic pathways or autophagy leading to cell death. Viruses are
      naturally evolved in hijacking the host cellular translation machinery to
      generate a large amount of proteins. This phenomenon disrupts ER homeostasis and
      leads to ER stress. Alternatively, in the case of gutted vectors used in gene
      therapy, the excess load of recombinant vectors administered and encountered by
      the cell can trigger UPR. Thus, in the context of gene therapy, UPR becomes a
      major roadblock that can potentially trigger inflammatory responses against the
      vectors and reduce the efficiency of gene transfer. 

PMID- 24904566
TI  - Vibrio ecology, pathogenesis, and evolution.

PMID- 24904567
TI  - Quantification of fungal abundance on cultural heritage using real time PCR
      targeting the beta-actin gene.
AB  - The traditional methodology used for the identification of microbes colonizing
      our cultural heritage was the application of cultivation methods and/or
      microscopy. This approach has many advantages, as living microorganisms may be
      obtained for physiological investigations. In addition, these techniques allow
      the quantitative and qualitative assessment of the investigated environment.
      Quantitative analyses are done by plate count and the determination of abundance
      by the colony forming unit (CFU). Nevertheless, these techniques have many
      drawbacks that lead to an underestimation of the cell numbers and do not provide
      a comprehensive overview of the composition of the inhabiting microbiota. In the
      last decades, several molecular techniques have been developed enabling many
      advantages over the cultivation approach. Mainly PCR-based, fingerprinting
      techniques allow a qualitative detection and identification of the microbiota. In
      this study, we developed a real time PCR method as a simple, rapid and reliable
      tool to detect and quantify fungal abundance using the beta-actin gene, which is
      known to appear as a single-copy gene in fungi. To this end, five different
      indoor thermal insulation materials applied for historical buildings that were
      previously tested for their bio-susceptibility against various fungi were
      subjected to qPCR analyses. The obtained results were compared with those
      obtained from a previous study investigating the bio-susceptibility of the
      insulation materials using classical cultivation experiments. Both results
      correlated well, revealing that Perlite plaster was the most suitable insulation
      material, showing the lowest fungal CFU and qPCR values. In contrast, insulations
      made of wood showed to be not recommendable from the microbiological point of
      view. In addition, the potential of qPCR was tested in other materials of
      cultural heritage, as old parchments, showing to be a suitable method for
      measuring fungal abundance in these delicate materials. 

PMID- 24904568
TI  - The life and fate of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) are present throughout the body and are thought to
      play a role in tissue regeneration and control of inflammation. MSC can be easily
      expanded in vitro and their potential as a therapeutic option for degenerative
      and inflammatory disease is therefore intensively investigated. Whilst it was
      initially thought that MSC would replace dysfunctional cells and migrate to sites
      of injury to interact with inflammatory cells, experimental evidence indicates
      that the majority of administered MSC get trapped in capillary networks and have
      a short life span. In this review, we discuss current knowledge on the migratory
      properties of endogenous and exogenous MSC and confer on how culture-induced
      modifications of MSC may affect these properties. Finally, we will discuss how,
      despite their limited survival, administered MSC can bring about their
      therapeutic effects. 

PMID- 24904569
TI  - The promising potential of menstrual stem cells for antenatal diagnosis and cell
      therapy.
AB  - Menstrual-derived stem cells (MenSCs) are a new source of mesenchymal stem cells
      isolated from the menstrual fluid. Currently, there is a growing interest in
      their clinical potential due to fact that they are multipotent, highly
      proliferative, and easy to obtain in a non-invasive manner. Sampling can be
      repeated periodically in a simplified and reproducible manner devoid of
      complications that no existing cell source can match. MenSCs are also free of
      ethical dilemmas, and display novel properties with regard to presently known
      adult derived stem cells. This review details their distinctive biological
      properties regarding immunophenotype and function, proliferation rate,
      differentiation potential, and paracrine effects mediated by secreted factors.
      Their possible role in antenatal diagnosis is also discussed. While more insight
      on their immunomodulatory and diagnostic properties is needed, the impact of
      clinical and epidemiological factors, such as age, use of contraceptives, or
      hormonal status still requires further investigations to properly assess their
      current and future use in clinical application and diagnosis. 

PMID- 24904570
TI  - Opportunistic Autoimmune Disorders Potentiated by Immune-Checkpoint Inhibitors
      Anti-CTLA-4 and Anti-PD-1.
AB  - To improve the efficacy of immunotherapy for cancer and autoimmune diseases,
      recent ongoing and completed clinical trials have focused on specific targets to
      redirect the immune network toward eradicating a variety of tumors and
      ameliorating the self-destructive process. In a previous review, both systemic
      immunomodulators and monoclonal antibodies (mAbs), anti-CTLA-4, and anti-CD52,
      were discussed regarding therapeutics and autoimmune sequelae, as well as
      predisposing factors known to exacerbate immune-related adverse events (irAEs).
      This review will focus on immune-checkpoint inhibitors, and the data from most
      clinical trials involve blockade with anti-CTLA-4 such as ipilimumab. However,
      despite the mild to severe irAEs observed with ipilimumab in ~60% of patients,
      overall survival (OS) averaged ~22-25% at 3-5 years. To boost OS, other mAbs
      targeting programed death-1 and its ligand are undergoing clinical trials as
      monotherapy or dual therapy with anti-CTLA-4. Therapeutic combinations may
      generate different spectrum of opportunistic autoimmune disorders. To simulate
      clinical scenarios, we have applied regulatory T cell perturbation to murine
      models combined to examine the balance between thyroid autoimmunity and tumor
      specific immunity. 

PMID- 24904571
TI  - Antigen-Specific Priming is Dispensable in Depletion of Apoptosis-Sensitive T
      Cells for GvHD Prophylaxis.
AB  - Prophylactic approaches to graft versus host disease (GvHD) have employed both
      phenotypic reduction of T cells and selective elimination of host-primed donor T
      cells in vitro and in vivo. An additional approach to GvHD prophylaxis by
      functional depletion of apoptosis-sensitive donor T cells without host-specific
      sensitization ex vivo showed remarkable reduction in GHD incidence and severity.
      We address the role and significance of antigen-specific sensitization of donor T
      cells and discuss the mechanisms of functional T cell purging by apoptosis for
      GvHD prevention. Host-specific sensitization is dispensable because migration is
      antigen-independent and donor T cell sensitization is mediated by multiple and
      redundant mechanisms of presentation of major and minor histocompatibility
      complex and tissue antigens by donor and host antigen-presenting cells. Our data
      suggest that potential murine and human GvH effectors reside within subsets of
      preactivated T cells susceptible to negative regulation by apoptosis prior to
      encounter of and sensitization to specific antigens. 

PMID- 24904572
TI  - HLA-C Incompatibilities in Allogeneic Unrelated Hematopoietic Stem Cell
      Transplantation.
AB  - An increasingly larger fraction of patients with hematological diseases are
      treated by hematopoietic stem cells transplantation (HSCT) from HLA matched
      unrelated donors. Polymorphisms of HLA genes represent a major barrier to HSCT
      because HLA-A, -B, -C and DRB1 incompatibilities confer a higher risk of acute
      graft-versus-host disease (aGVHD) and mortality. Although >22 million volunteer
      HLA-typed donors are available worldwide, still a significant number of patients
      do not find a highly matched HSC donor. Because of the large haplotypic diversity
      in HLA-B-C associations, incompatibilities occur most frequently at HLA-C, so
      that unrelated donors with a single HLA-C mismatch often represent the only
      possible choice. The ratio of HLA-C-mismatched HSCT over the total number of
      transplants varies from 15 to 30%, as determined in 12 multicenter studies. Six
      multicenter studies involving >1800 patients have reported a 21-43% increase in
      mortality risk. By using in vitro cellular assays, a large heterogeneity in T
      cell allorecognition has been observed. Yet the permissiveness of individual HLA
      C mismatches remains poorly defined. It could be linked to the position and
      nature of the mismatched residues on HLA-C molecules, but also to variability in
      the expression levels of the mismatched alleles. The permissive C*03:03-03:04
      mismatch is characterized by full compatibility at residues 9, 97, 99, 116, 152,
      156, and 163 reported to be key positions influencing T-cell allorecognition.
      With a single difference among these seven key residues the C*07:01-07:02
      mismatch might also be considered by analogy as permissive. High variability of
      HLA-C expression as determined by quantitative RT-PCR has been observed within
      individual allotypes and shows some correlation with A-B-C-DRB1 haplotypes. Thus
      in addition to the position of mismatched amino acid residues, expression level
      of patient's mismatched HLA-C allotype might influence T-cell allorecognition,
      with patients low expression-C alleles representing possible permissive
      mismatches. 

PMID- 24904573
TI  - Dendritic Cell Therapy in an Allogeneic-Hematopoietic Cell Transplantation
      Setting: An Effective Strategy toward Better Disease Control?
AB  - Hematopoietic cell transplantation (HCT) is a last treatment resort and only
      potentially curative treatment option for several hematological malignancies
      resistant to chemotherapy. The induction of profound immune regulation after
      allogeneic HCT is imperative to prevent graft-versus-host reactions and, at the
      same time, allow protective immune responses against pathogens and against tumor
      cells. Dendritic cells (DCs) are highly specialized antigen-presenting cells that
      are essential in regulating this balance and are of major interest as a tool to
      modulate immune responses in the complex and challenging phase of immune
      reconstitution early after allo-HCT. This review focuses on the use of DC
      vaccination to prevent cancer relapses early after allo-HCT. It describes the
      role of host and donor-DCs, various vaccination strategies, different DC subsets,
      antigen loading, DC maturation/activation, and injection sites and dose. At last,
      clinical trials using DC vaccination post-allo-HCT and the future perspectives of
      DC vaccination in combination with other cancer immunotherapies are discussed. 

PMID- 24904574
TI  - The T-Cell Response to Lipid Antigens of Mycobacterium tuberculosis.
AB  - T-cells recognize lipid antigens presented by dedicated antigen-presenting
      molecules that belong to the CD1 family. This review discusses the structural
      properties of CD1 molecules, the nature of mycobacterial lipid antigens, and the
      phenotypic and functional properties of T-cells recognizing mycobacterial lipids.
      In humans, the five CD1 genes encode structurally similar glycoproteins that
      recycle in and thus survey different cellular endosomal compartments. The
      structure of the CD1-lipid-binding pockets, their mode of intracellular recycling
      and the type of CD1-expressing antigen-presenting cells all contribute to
      diversify lipid immunogenicity and presentation to T-cells. Mycobacteria produce
      a large variety of lipids, which form stable complexes with CD1 molecules and
      stimulate specific T-cells. The structures of antigenic lipids may be greatly
      different from each other and each lipid may induce unique T-cells capable of
      discriminating small lipid structural changes. The important functions of some
      lipid antigens within mycobacterial cells prevent the generation of negative
      mutants capable of escaping this type of immune response. T-cells specific for
      lipid antigens are stimulated in tuberculosis and exert protective functions. The
      mechanisms of antigen recognition, the type of effector functions and the mode of
      lipid-specific T-cell priming are discussed, emphasizing recent evidence of the
      roles of lipid-specific T-cells in tuberculosis. 

PMID- 24904575
TI  - TLR-CD40 Cross-Talk in Anti-Leishmanial Immune Response.

PMID- 24904577
TI  - Higher Expression of Activating Receptors on Cytotoxic NK Cells is Associated
      with Early Control on HIV-1C Multiplication.
AB  - Natural killer (NK) cells may be important in modulating HIV replication in early
      course of HIV infection. The effector function of NK cells is finely tuned by a
      balance between signals delivered by activating and inhibitory receptors.
      However, the influence of expression of these receptors on the early course of
      HIV replication and subsequent disease progression is not explored in the context
      of HIV-1C infection. The expression pattern of activating (NKp46, NKp44, NKp30,
      NKG2D, and NKG2C) and inhibitory (CD158b, NKG2A, and ILT2) receptors was
      determined in 20 patients with recent HIV-1C infection within 3-7 months of
      acquiring HIV infection and was compared with the expression pattern in
      individuals with progressive (N = 12), non-progressive HIV-1C infection (LTNPs, N
      = 12) and healthy seronegative individuals (N = 20). The association of the
      expression of these receptors on the rate of disease progression was assessed
      using viral load set point of recently infected individuals as a marker of
      disease progression. The study showed that higher cytotoxic potency of NK cells
      was associated with low viral load set point in recent HIV infection (r = -0.701;
      p = 0.0006) and higher CD4 counts (r = 0.720; p = 0.001). The expression of
      activating receptors (NKp46, NKp30, and NKG2D) on cytotoxic NK cells but not on
      regulatory NK cells was also significantly associated with low viral set point (p
      < 0.01) and viral load in LTNPs and progressors (p < 0.01). The study also
      indicated that cytotoxic NK cells might show the ability to specifically lyse HIV
      infected CD4 cells. This data collectively showed that early and sustained higher
      expression of activating receptors on cytotoxic NK cells could be responsible for
      increased cytotoxicity, reduced viral burden, and thus delaying the disease
      progression. The study to identify the molecular mechanism of the expression of
      these receptors in HIV infection will be helpful in further understanding of NK
      cell mediated control in early HIV infection. 

PMID- 24904576
TI  - Role of toll-like receptors in immune activation and tolerance in the liver.
AB  - Liver has a unique vascular system receiving the majority of the blood supply
      from the gastrointestinal tract through the portal vein and faces continuous
      exposure to foreign pathogens and commensal bacterial products. These gut-derived
      antigens stimulate liver cells and result in a distinctive immune response via a
      family of pattern recognition receptors, the Toll-like receptors (TLRs). TLRs are
      expressed on Kupffer cells, dendritic cells, hepatic stellate cells, endothelial
      cells, and hepatocytes in the liver. The crosstalk between gut-derived antigens
      and TLRs on immune cells trigger a distinctive set of mechanisms to induce
      immunity, contributing to various acute and chronic liver diseases including
      liver cirrhosis and hepatocellular carcinoma. Accumulating evidence has shown
      that TLRs stimulation by foreign antigens induces the production of
      immunoactivating and immunoregulatory cytokines. Furthermore, the
      immunoregulatory arm of TLR stimulation can also control excessive tissue damage.
      With this knowledge at hand, it is important to clarify the dual role of disease
      specific TLRs as activators and regulators, especially in the liver. We will
      review the current understanding of TLR signaling and subsequent immune
      activation and tolerance by the innate immune system in the liver. 

PMID- 24904578
TI  - Toll-like receptor mediated regulation of breast cancer: a case of mixed
      blessings.

PMID- 24904579
TI  - Phenotypic changes in growth-arrested T cell hybrids: a possible avenue to
      produce functional T cell hybridoma.

PMID- 24904581
TI  - Mast cell-mediated and associated disorders in pregnancy: a risky game with an
      uncertain outcome?
AB  - During pregnancy, the maternal organism is under the influence of tremendous
      endocrine as well as immunological changes as an adaptation to the implanted and
      developing fetus. In most cases, the maternal adaptations to pregnancy ensure
      both, the protection against harmful pathogens and the tolerance toward the
      growing semi-allogeneic fetus. However, under certain circumstances the unique
      hormonal milieu during pregnancy is causative of a shift into an unfavorable
      direction. Of particular importance are cellular disorders previous to pregnancy
      that involve cell types known for their susceptibility to hormones. One
      interesting cell type is the mast cell (MC), one of the key figures in allergic
      disorders. While physiological numbers of MCs were shown to positively influence
      pregnancy outcome, at least in mouse models, uncontrolled augmentations in
      quantity, and/or activation can lead to pregnancy complications. Women that have
      the desire of getting pregnant and been diagnosed with MC mediated disorders such
      as urticaria and mastocytosis or chronic inflammatory diseases in which MCs are
      involved, including atopic dermatitis, asthma, or psoriasis, may benefit from
      specialized medical assistance to ensure a positive pregnancy outcome. In the
      present review, we address the course of pregnancy in women affected by MC
      mediated or associated disorders. 

PMID- 24904580
TI  - The role of placental tryptophan catabolism.
AB  - This review discusses the mechanisms and consequences of degradation of
      tryptophan (Trp) in the placenta, focusing mainly on the role of indoleamine 2,3
      dioxygenase-1 (IDO1), one of three enzymes catalyzing the first step of the
      kynurenine pathway of Trp degradation. IDO1 has been implicated in regulation of
      feto-maternal tolerance in the mouse. Local depletion of Trp and/or the presence
      of metabolites of the kynurenine pathway mediate immunoregulation and exert
      antimicrobial functions. In addition to the decidual glandular epithelium, IDO1
      is localized in the vascular endothelium of the villous chorion and also in the
      endothelium of spiral arteries of the decidua. Possible consequences of IDO1
      mediated catabolism of Trp in the endothelium encompass antimicrobial activity
      and immunosuppression, as well as relaxation of the placental vasotonus, thereby
      contributing to placental perfusion and growth of both placenta and fetus. It
      remains to be evaluated whether other enzymes mediating Trp oxidation, such as
      indoleamine 2,3-dioxygenase-2, Trp 2,3-dioxygenase, and Trp hydroxylase-1 are of
      relevance to the biology of the placenta. 

PMID- 24904582
TI  - Characterization of Novel PI3Kdelta Inhibitors as Potential Therapeutics for SLE
      and Lupus Nephritis in Pre-Clinical Studies.
AB  - SLE is a complex autoimmune inflammatory disease characterized by pathogenic
      autoantibody production as a consequence of uncontrolled T-B cell activity and
      immune-complex deposition in various organs, including kidney, leading to tissue
      damage and function loss. There is a high unmet need for better treatment options
      other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase delta
      (PI3Kdelta) is a promising target in this respect as it is essential in mediating
      B- and T-cell function in mouse and human. We report the identification of
      selective PI3Kdelta inhibitors that blocked B-, T-, and plasmacytoid dendritic
      cell activities in human peripheral blood and in primary cell co-cultures
      (BioMAP((r))) without detecting signs of undesired toxicity. In an IFNalpha
      accelerated mouse SLE model, our PI3Kdelta inhibitors blocked nephritis
      development, whether administered at the onset of autoantibody appearance or the
      onset of proteinuria. Disease amelioration correlated with normalized immune cell
      numbers in the spleen, reduced immune-complex deposition as well as reduced
      inflammation, fibrosis, and tissue damage in the kidney. Improvements were
      similar to those achieved with a frequently prescribed drug for lupus nephritis,
      the potent immunosuppressant mycophenolate mofetil. Finally, we established a
      pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained
      PI3Kdelta inhibition of 50% is sufficient to achieve full efficacy in our disease
      model. These data demonstrate the therapeutic potential of PI3Kdelta inhibitors
      in SLE and lupus nephritis. 

PMID- 24904583
TI  - Immune responses to inhalant Mammalian allergens.
AB  - In Europe and the USA, at least one person in four is exposed every day to
      inhalant allergens of mammalian origin, a considerable number is regularly
      exposed for professional reasons and almost everyone is occasionally exposed to
      inhalant allergens from pets or domestic animals. The production of IgE to these
      inhalant allergens, often complicated by asthma and rhinitis, defines the atopic
      status. However, the immune response to these allergens largely imprints the
      cellular immune compartment and also drives non-IgE humoral immune responses in
      the allergic and non-allergic population. During the recent years, it has become
      clear that IgE antibodies recognize mammalian allergens that belong to three
      protein or glycoprotein families: the secretoglobins, the lipocalins, and the
      serum albumins. In this article, we review the humoral and cellular immune
      responses to the major members of these families and try to define common
      characteristics and also distinctive features. 

PMID- 24904584
TI  - The PGRS Domain from PE_PGRS33 of Mycobacterium tuberculosis is Target of Humoral
      Immune Response in Mice and Humans.
AB  - The PE_PGRS33 protein is a member of the PE family, which encompasses the PE and
      the PE_PGRS subfamilies. Among PE_PGRS's, this protein is one of the most studied
      antigens and its immunomodulatory properties are influence by both PE and PGRS
      domains. However, the contribution of these domains to the host immune
      recognition of the PE_PGRS33 protein and their potential role in latent
      tuberculosis infection in humans is still unknown. In this study, the immunogenic
      properties of the complete PE_PGRS33 protein and each domain separately were
      evaluated in BALB/c mice and latent tuberculosis infected (LTBI) humans. In mice,
      PE_PGRS33 and its domains induced similar antibody production and secretion of
      IFN-gamma. PE_PGRS33 and the PE domain stimulated higher CD4(+) and CD8(+) T-cell
      proliferation compared to the PGRS domain. This demonstrated that the principal
      difference in the immune recognition of the domains is the higher activation of T
      cell subpopulations involved in the control of tuberculosis. In humans, the
      secretion of IFN-gamma in response to PE_PGRS33 was detected in both LTBI and in
      non-infected vaccinated individuals. The same was observed for antibody response,
      which targets epitopes located in the PGRS domain but not in the PE domain. These
      observations suggest that T and B cell responses to PE_PGRS33 are induced by BCG
      vaccination and can be maintained for many years in non-infected individuals.
      This also indicates that the IFN-gamma response detected might not be associated
      with latent tuberculosis infection. These results contribute to the elucidation
      of the role of the PE_PGRS33 protein and its PE and PGRS domains in the immune
      response against Mycobacterium tuberculosis. 

PMID- 24904585
TI  - A major hindrance in antibody affinity maturation investigation: we never
      succeeded in falsifying the hypothesis of single-step selection.

PMID- 24904586
TI  - Plasmacytoid Dendritic Cells: Neglected Regulators of the Immune Response to
      Staphylococcus aureus.
AB  - Plasmacytoid dendritic cells (pDC) are a rare subset of leukocytes equipped with
      Fcgamma and Fcepsilon receptors, which exert contrary effects on sensing of
      microbial nucleic acids by endosomal Toll-like receptors. In this article, we
      explain how pDC contribute to the immune response to Staphylococcus aureus. Under
      normal circumstances the pDC participates in the memory response to the pathogen:
      pDC activation is initiated by uptake of staphylococcal immune complexes with IgG
      or IgE. However, protein A-expressing S. aureus strains additionally trigger pDC
      activation in the absence of immunoglobulin. In this context, staphylococci
      exploit the pDC to induce antigen-independent differentiation of IL-10 producing
      plasmablasts, an elegant means to propagate immune evasion. We further discuss
      the role of type I interferons in infection with S. aureus and the implications
      of these findings for the development of immune based therapies and vaccination. 

PMID- 24904587
TI  - Harnessing Human Cross-Presenting CLEC9A(+)XCR1(+) Dendritic Cells for
      Immunotherapy.

PMID- 24904588
TI  - A novel pax5-binding regulatory element in the igkappa locus.
AB  - The Igkappa locus undergoes a variety of different molecular processes during B
      cell development, including V(D)J rearrangement and somatic hypermutations (SHM),
      which are influenced by cis regulatory regions (RRs) within the locus. The
      Igkappa locus includes three characterized RRs termed the intronic (iEkappa),
      3'Ekappa, and Ed enhancers. We had previously noted that a region of DNA upstream
      of the iEkappa and matrix attachment region (MAR) was necessary for demethylation
      of the locus in cell culture. In this study, we further characterized this
      region, which we have termed Dm, for demethylation element. Pre-rearranged
      Igkappa transgenes containing a deletion of the entire Dm region, or of a Pax5
      binding site within the region, fail to undergo efficient CpG demethylation in
      mature B cells in vivo. Furthermore, we generated mice with a deletion of the
      full Dm region at the endogenous Igkappa locus. The most prominent phenotype of
      these mice is reduced SHM in germinal center B cells in Peyer's patches. In
      conclusion, we propose the Dm element as a novel Pax5-binding cis regulatory
      element, which works in concert with the known enhancers, and plays a role in
      Igkappa demethylation and SHM. 

PMID- 24904589
TI  - Biomarkers of safety and immune protection for genetically modified live
      attenuated leishmania vaccines against visceral leishmaniasis - discovery and
      implications.
AB  - Despite intense efforts there is no safe and efficacious vaccine against visceral
      leishmaniasis, which is fatal and endemic in many tropical countries. A major
      shortcoming in the vaccine development against blood-borne parasitic agents such
      as Leishmania is the inadequate predictive power of the early immune responses
      mounted in the host against the experimental vaccines. Often immune correlates
      derived from in-bred animal models do not yield immune markers of protection that
      can be readily extrapolated to humans. The limited efficacy of vaccines based on
      DNA, subunit, heat killed parasites has led to the realization that acquisition
      of durable immunity against the protozoan parasites requires a controlled
      infection with a live attenuated organism. Recent success of irradiated malaria
      parasites as a vaccine candidate further strengthens this approach to
      vaccination. We developed several gene deletion mutants in Leishmania donovani as
      potential live attenuated vaccines and reported extensively on the immunogenicity
      of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited
      studies using genetically modified live attenuated Leishmania parasites as
      vaccine candidates have been reported. However, for the live attenuated parasite
      vaccines, the primary barrier against widespread use remains the absence of clear
      biomarkers associated with protection and safety. Recent studies in evaluation of
      vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools
      demonstrated the power of such strategies in understanding the immunological
      mechanisms that underpin a protective phenotype. Applying similar tools in
      isolated human tissues such as PBMCs from healthy individuals infected with live
      attenuated parasites such as LdCen(-/-) in vitro followed by human microarray
      hybridization experiments will enable us to understand how early vaccine-induced
      gene expression profiles and the associated immune responses are coordinately
      regulated in normal individuals. In addition, comparative analysis of biomarkers
      in PBMCs from asymptomatic or healed visceral leishmaniasis individuals in
      response to vaccine candidates including live attenuated parasites may provide
      clues about determinants of protective immunity and be helpful in shaping the
      final Leishmania vaccine formulation in the clinical trials. 

PMID- 24904590
TI  - The unique neonatal NK cells: a critical component required for neonatal
      autoimmune disease induction by maternal autoantibody.
AB  - Human maternal autoantibodies can trigger autoimmune diseases such as congenital
      heart block (CHB) in the progeny of women with lupus or Sjogren's disease. The
      pathogenic effect of early autoantibody (autoAb) exposure has been investigated
      in a murine neonatal autoimmune ovarian disease (nAOD) model triggered by a
      unique ZP3 antibody. Although immune complexes (IC) are formed in adult and
      neonatal ovaries, ZP3 antibody triggers severe nAOD only in <7-day-old neonatal
      mice. Propensity to nAOD is due to the uniquely hyper-responsive neonatal natural
      killer (NK) cells that lack the inhibitory Ly49C/I receptors. In nAOD, the
      neonatal NK cells directly mediate ovarian inflammation and oocyte depletion
      while simultaneously promoting de novo pathogenic ovarian-specific T cell
      responses. Resistance to nAOD in older mice results from the emergence of the
      Ly49C/I(+) NK cells that regulate effector NK cells and from CD25(+) regulatory T
      cell control. In preliminary studies, FcgammaRIII(+) NK cells as well as the
      ovarian resident FcgammaRIII(+) macrophages and/or dendritic cells were found to
      be as indispensable players. Activated by ovarian IC, they migrate to lymphoid
      organs where NK cell priming occurs. Remarkably, the findings in nAOD are very
      similar to those reported for neonatal responses to a retrovirus and its cognate
      antibody that lead to long-lasting immunity. Studies on nAOD therefore provide
      insights into maternal autoAb-mediated neonatal autoimmunity, including CHB,
      while simultaneously uncovering new properties of the neonatal innate and
      adaptive responses, lethality of premature infant infection, and novel neonatal
      antiviral vaccine design. 

PMID- 24904592
TI  - Hepatitis C-associated mixed cryoglobulinemic vasculitis induces differential
      gene expression in peripheral mononuclear cells.
AB  - This study examines the distinct gene expression profile of peripheral blood
      mononuclear cells from patients with chronic hepatitis C infection and mixed
      cryoglobulinemic (MC) vasculitis. Our DNA microarray analysis indicates that
      hepatitis C virus (HCV)-associated MC vasculitis is characterized by compromised
      neutrophil function, impaired chemotaxis, and increased interferon-stimulated
      gene (ISG) expression, contributing to overall MC pathogenesis and end-organ
      damage. Increased ISG expression is suggestive of an enhanced endogenous
      interferon gene signature. PBMC depletion assays demonstrate that this increased
      expression is likely due to an activation of monocytes and not a direct result of
      B cell expansion. Notably, this monocyte activation of ISG expression in HCV
      associated MC vasculitis suggests a poor predictor status of interferon-based
      treatment. Further analysis of PBMC gene expression profiles before and after in
      vivo B cell depletion therapy is critical to completely understanding the
      mechanisms of MC vasculitis pathogenesis. 

PMID- 24904591
TI  - Innate immune system and preeclampsia.
AB  - Normal pregnancy is considered as a Th2 type immunological state that favors an
      immune-tolerance environment in order to prevent fetal rejection. Preeclampsia
      (PE) has been classically described as a Th1/Th2 imbalance; however, the Th1/Th2
      paradigm has proven insufficient to fully explain the functional and molecular
      changes observed during normal/pathological pregnancies. Recent studies have
      expanded the Th1/Th2 into a Th1/Th2/Th17 and regulatory T-cells paradigm and
      where dendritic cells could have a crucial role. Recently, some evidence has
      emerged supporting the idea that mesenchymal stem cells might be part of the feto
      maternal tolerance environment. This review will discuss the involvement of the
      innate immune system in the establishment of a physiological environment that
      favors pregnancy and possible alterations related to the development of PE. 

PMID- 24904594
TI  - Mouse Model of Devil Facial Tumour Disease Establishes That an Effective Immune
      Response Can be Generated Against the Cancer Cells.
AB  - The largest carnivorous marsupial in Australia, the Tasmanian devil (Sarcophilus
      harrisii) is facing extinction in the wild due to a transmissible cancer known as
      Devil Facial Tumour Disease (DFTD). DFTD is a clonal cell line transmitted from
      host to host with 100% mortality and no known immunity. While it was first
      considered that low genetic diversity of the population of devils enabled the
      allograft transmission of DFTD recent evidence reveals that genetically diverse
      animals succumb to the disease. The lack of an immune response against the DFTD
      tumor cells may be due to a lack of immunogenicity of the tumor cells. This could
      facilitate transmission between devils. To test immunogenicity, mice were
      injected with viable DFTD cells and anti-DFTD immune responses analyzed. A range
      of antibody isotypes against DFTD cells was detected, indicating that as DFTD
      cells can induce an immune response they are immunogenic. This was supported by
      cytokine production, when splenocytes from mice injected with DFTD cells were
      cultured in vitro with DFTD cells and the supernatant analyzed. There was a
      significant production of IFN-gamma and TNF-alpha following the first injection
      with DFTD cells and a significant production of IL-6 and IL-10 following the
      second injection. Splenocytes from naive or immunized mice killed DFTD cells in
      in vitro cytotoxicity assays. Thus, they are also targets for immunological
      destruction. We conclude that as an immune response can be generated against DFTD
      cells they would be suitable targets for a vaccine. 

PMID- 24904593
TI  - NOTCH1 Can Initiate NF-kappaB Activation via Cytosolic Interactions with
      Components of the T Cell Signalosome.
AB  - T cell stimulation requires the input and integration of external signals.
      Signaling through the T cell receptor (TCR) is known to induce formation of the
      membrane-tethered CBM complex, comprising CARMA1, BCL10, and MALT1, which is
      required for TCR-mediated NF-kappaB activation. TCR signaling has been shown to
      activate NOTCH proteins, transmembrane receptors also implicated in NF-kappaB
      activation. However, the link between TCR-mediated NOTCH signaling and early
      events leading to induction of NF-kappaB activity remains unclear. In this
      report, we demonstrate a novel cytosolic function for NOTCH1 and show that it is
      essential to CBM complex formation. Using a model of skin allograft rejection, we
      show in vivo that NOTCH1 acts in the same functional pathway as PKCtheta, a T
      cell-specific kinase important for CBM assembly and classical NF-kappaB
      activation. We further demonstrate in vitro NOTCH1 associates physically with
      PKCtheta and CARMA1 in the cytosol. Unexpectedly, when NOTCH1 expression was
      abrogated using RNAi approaches, interactions between CARMA1, BCL10, and MALT1
      were lost. This failure in CBM assembly reduced inhibitor of kappa B alpha
      phosphorylation and diminished NF-kappaB-DNA binding. Finally, using a luciferase
      gene reporter assay, we show the intracellular domain of NOTCH1 can initiate
      robust NF-kappaB activity in stimulated T cells, even when NOTCH1 is excluded
      from the nucleus through modifications that restrict it to the cytoplasm or hold
      it tethered to the membrane. Collectively, these observations provide evidence
      that NOTCH1 may facilitate early events during T cell activation by nucleating
      the CBM complex and initiating NF-kappaB signaling. 

PMID- 24904595
TI  - Pathobiology of salmonella, intestinal microbiota, and the host innate immune
      response.
AB  - Salmonella is a relevant pathogen under a clinical and public health perspective.
      Therefore, there has been a significant scientific effort to learn about
      pathogenic determinants of this pathogen. The clinical relevance of the disease,
      associated with the molecular tools available to study Salmonella as well as
      suitable animal models for salmonellosis, have provided optimal conditions to
      drive the scientific community to generate a large expansion of our knowledge
      about the pathogenesis of Salmonella-induced enterocolitis that took place during
      the past two decades. This research effort has also generated a wealth of
      information on the host immune mechanisms that complements gaps in the
      fundamental research in this area. This review focus on how the interaction
      between Salmonella, the microbiota and intestinal innate immunity leads to
      disease manifestation. As a highly successful enteropathogen, Salmonella actively
      elicits a robust acute intestinal inflammatory response from the host, which
      could theoretically lead to the pathogen demise. However, Salmonella has evolved
      redundant molecular machineries that renders this pathogen highly adapted to the
      inflamed intestinal environment, in which Salmonella is capable of outcompete
      resident commensal organisms. The adaptation of Salmonella to the inflamed
      intestinal lumen associated with the massive inflammatory response that leads to
      diarrhea, generate perfect conditions for transmission of the pathogen. These
      conditions illustrate the complexity of the co-evolution and ecology of the
      pathogen, commensals, and the host. 

PMID- 24904596
TI  - Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10
      during Pregnancy.
AB  - Inflammation mediated by both innate and adaptive immune cells is necessary for
      several important processes during pregnancy. Pro-inflammatory immune cell
      activation plays a critical role in embryo implantation, placentation, and
      parturition; however dysregulation of these cells can lead to detrimental
      pregnancy outcomes including spontaneous abortion, fetal growth restriction,
      maternal pathology including hypertensive disorders, or fetal and maternal death.
      The resolution of inflammation plays an important role throughout pregnancy and
      is largely mediated by immune cells that produce interleukin (IL)-4 and IL-10.
      The temporal and spatial aspects of reducing inflammation during pregnancy
      represent a complex process that if not functioning optimally can lead to
      persistent inflammation and pregnancy complications. In this review, we examine
      how immune cells that produce IL-4 and IL-10 are regulated throughout pregnancy
      as well as the effects that reduced IL-4 and IL-10 signaling has on fetal and
      maternal physiology. 

PMID- 24904597
TI  - The transcriptional regulatory network in the drought response and its crosstalk
      in abiotic stress responses including drought, cold, and heat.
AB  - Drought negatively impacts plant growth and the productivity of crops around the
      world. Understanding the molecular mechanisms in the drought response is
      important for improvement of drought tolerance using molecular techniques. In
      plants, abscisic acid (ABA) is accumulated under osmotic stress conditions caused
      by drought, and has a key role in stress responses and tolerance. Comprehensive
      molecular analyses have shown that ABA regulates the expression of many genes
      under osmotic stress conditions, and the ABA-responsive element (ABRE) is the
      major cis-element for ABA-responsive gene expression. Transcription factors (TFs)
      are master regulators of gene expression. ABRE-binding protein and ABRE-binding
      factor TFs control gene expression in an ABA-dependent manner. SNF1-related
      protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were
      shown to control the ABA signaling pathway. ABA-independent signaling pathways
      such as dehydration-responsive element-binding protein TFs and NAC TFs are also
      involved in stress responses including drought, heat, and cold. Recent studies
      have suggested that there are interactions between the major ABA signaling
      pathway and other signaling factors in stress responses. The important roles of
      these TFs in crosstalk among abiotic stress responses will be discussed. Control
      of ABA or stress signaling factor expression can improve tolerance to
      environmental stresses. Recent studies using crops have shown that stress
      specific overexpression of TFs improves drought tolerance and grain yield
      compared with controls in the field. 

PMID- 24904599
TI  - Silica uptake by Spartina-evidence of multiple modes of accumulation from salt
      marshes around the world.
AB  - Silicon (Si) plays a critical role in plant functional ecology, protecting plants
      from multiple environmental stressors. While all terrestrial plants contain some
      Si, wetland grasses are frequently found to have the highest concentrations,
      although the mechanisms driving Si accumulation in wetland grasses remain in
      large part uncertain. For example, active Si accumulation is often assumed to be
      responsible for elevated Si concentrations found in wetland grasses. However,
      life stage and differences in Si availability in the surrounding environment also
      appear to be important variables controlling the Si concentrations of wetland
      grasses. Here we used original data from five North American salt marshes, as
      well as all known published literature values, to examine the primary drivers of
      Si accumulation in Spartina, a genus of prolific salt marsh grasses found
      worldwide. We found evidence of multiple modes of Si accumulation in Spartina,
      with passive accumulation observed in non-degraded marshes where Spartina was
      native, while rejective accumulation was found in regions where Spartina was
      invasive. Evidence of active accumulation was found in only one marsh where
      Spartina was native, but was also subjected to nutrient over-enrichment. We
      developed a conceptual model which hypothesizes that the mode of Si uptake by
      Spartina is dependent on local environmental factors and genetic origin,
      supporting the idea that plant species should be placed along a spectrum of Si
      accumulation. We hypothesize that Spartina exhibits previously unrecognized
      phenotypic plasticity with regard to Si accumulation, allowing these plants to
      respond to changes in marsh condition. These results provide new insight
      regarding how salt marsh ecosystems regulate Si exchange at the land-sea
      interface. 

PMID- 24904598
TI  - On the role of some ARGONAUTE proteins in meiosis and DNA repair in Arabidopsis
      thaliana.
AB  - In plants, small non-coding RNAs (~20-30 nt) play a major role in a gene
      regulation mechanism that controls development, maintains heterochromatin and
      defends against viruses. However, their possible role in cell division (mitosis
      and meiosis) still remains to be ascertained. ARGONAUTE (AGO) proteins are key
      players in the different small RNA (sRNA) pathways. Arabidopsis contains 10 AGO
      proteins belonging to three distinct phylogenetic clades based on amino acid
      sequence, namely: AGO1/AGO5/AGO10, AGO2/AGO3/AGO7, and AGO4/AGO6/AGO8/AGO9. To
      gain new insights into the role of AGO proteins, we have focused our attention on
      AGO2, AGO5, and AGO9 by means of the analysis of plants carrying mutations in the
      corresponding genes. AGO2 plays a role in the natural cis-antisense (nat-siRNA)
      pathway and is required for an efficient DNA repair. On the other hand, AGO5,
      involved in miRNA (microRNA)-directed target cleavage, and AGO9, involved in RNA
      directed DNA methylation (RdDM), are highly enriched in germline. On these
      grounds, we have analyzed the effects of these proteins on the meiotic process
      and also on DNA repair. It was confirmed that AGO2 is involved in DNA repair. In
      ago2-1 the mean cell chiasma frequency in pollen mother cells (PMCs) was
      increased relative to the wild-type (WT). ago5-4 showed a delay in germination
      time and a slight decrease in fertility, however the meiotic process and chiasma
      levels were normal. Meiosis in PMCs of ago9-1 was characterized by a high
      frequency of chromosome interlocks from pachytene to metaphase I, but chiasma
      frequency and fertility were normal. Genotoxicity assays have confirmed that AGO9
      is also involved in somatic DNA repair. 

PMID- 24904601
TI  - Structural and functional basis for starch binding in the SnRK1 subunits
      AKINbeta2 and AKINbetagamma.
AB  - Specialized carbohydrate-binding domains, the Starch-Binding Domain (SBD) and the
      Glycogen Binding Domain (GBD), are motifs of approximately 100 amino acids
      directly or indirectly associated with starch or glycogen metabolism. Members of
      the regulatory beta subunit of the heterotrimeric complex AMPK/SNF1/SnRK1 contain
      an SBD or GBD. In Arabidopsis thaliana, the beta regulatory subunit AKINbeta2 and
      a gamma-type subunit, AKINbetagamma, also have an SBD. In this work, we compared
      the SBD of AKINbeta2 and AKINbetagamma with the GBD present in rat AMPKbeta1 and
      demonstrated that they conserved the same overall topology. The majority of the
      amino acids identified in the protein-carbohydrate interactions in the rat
      AMPKbeta1 are conserved in the two plant proteins. In AKINbetagamma, there is an
      insertion of three amino acids that creates a loop adjacent to one of the
      conserved tryptophan residues. Functionally, the SBD from AKINbetagamma and
      AKINbeta2 could bind starch, but there was an important difference in the
      association when an amylose/amylopectin (A/A) mixture was used. The physiological
      relevance of binding to starch was clear for AKINbetagamma, because
      immunolocalization experiments identified this protein inside the chloroplast.
      SnRK1 activity was not affected by the addition of A/A to the reaction mixture.
      However, addition of starch inhibited the activity 85%. Furthermore, proteins
      associated with A/A and starch in an in vitro-binding assay accounted for 10-20%
      of total SnRK1 kinase activity. Interestingly, the identification of the SnRK1
      subunits associated to the protein-carbohydrate complex indicated that only the
      catalytic subunits, AKIN10 and AKIN11, and the regulatory subunit AKINbetagamma
      were present. These results suggest that a dimer formed between either catalytic
      subunit and AKINbetagamma could be associated with the A/A mixture in its active
      form but the same subunits are inactivated when binding to starch. 

PMID- 24904602
TI  - Overcoming barriers to seedling regeneration during forest restoration on
      tropical pasture land and the potential value of woody weeds.
AB  - Combating the legacy of deforestation on tropical biodiversity requires the
      conversion to forest of large areas of established pasture, where barriers to
      native plant regeneration include competition with pasture grasses and poor
      propagule supply (seed availability). In addition, initial woody plants that
      colonise pasture are often invasive, non-native species whose ecological roles
      and management in the context of forest regeneration are contested. In a
      restoration experiment at two 0.64 ha sites we quantified the response of native
      woody vegetation recruitment to (1) release from competition with introduced
      pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal
      provided by scattered woody plants and artificial bird perches. Herbicide pasture
      grass suppression during 20 months caused a significant but modest increase in
      density of native woody seedlings, together with abundant co-recruitment of the
      prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of
      native species was further enhanced by local structure in herbicide-treated
      areas, being consistently greater under live trees and dead non-native shrubs
      (herbicide-treated) than in open areas, and intermediate under bird perches.
      Native seedling recruitment comprised 28 species across 0.25 ha sampled but was
      dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias
      murrayi). These early results are consistent with the expected increase in woody
      vegetation recruitment in response to release from competitive and dispersive
      barriers to rainforest regeneration. The findings highlight the need for a
      pragmatic consideration of the ecological roles of woody weeds and the potential
      roles of "new forests" more broadly in accelerating succession of humid tropical
      forest across large areas of retired agricultural land. 

PMID- 24904600
TI  - Mechanisms of regulation of SNF1/AMPK/SnRK1 protein kinases.
AB  - The SNF1 (sucrose non-fermenting 1)-related protein kinases 1 (SnRKs1) are the
      plant orthologs of the budding yeast SNF1 and mammalian AMPK (AMP-activated
      protein kinase). These evolutionarily conserved kinases are metabolic sensors
      that undergo activation in response to declining energy levels. Upon activation,
      SNF1/AMPK/SnRK1 kinases trigger a vast transcriptional and metabolic reprograming
      that restores energy homeostasis and promotes tolerance to adverse conditions,
      partly through an induction of catabolic processes and a general repression of
      anabolism. These kinases typically function as a heterotrimeric complex composed
      of two regulatory subunits, beta and gamma, and an alpha-catalytic subunit, which
      requires phosphorylation of a conserved activation loop residue for activity.
      Additionally, SNF1/AMPK/SnRK1 kinases are controlled by multiple mechanisms that
      have an impact on kinase activity, stability, and/or subcellular localization.
      Here we will review current knowledge on the regulation of SNF1/AMPK/SnRK1 by
      upstream components, post-translational modifications, various metabolites,
      hormones, and others, in an attempt to highlight both the commonalities of these
      essential eukaryotic kinases and the divergences that have evolved to cope with
      the particularities of each one of these systems. 

PMID- 24904603
TI  - Biochemical quantitation of the eIF5A hypusination in Arabidopsis thaliana
      uncovers ABA-dependent regulation.
AB  - The eukaryotic translation elongation factor eIF5A is the only protein known to
      contain the unusual amino acid hypusine which is essential for its biological
      activity. This post-translational modification is achieved by the sequential
      action of the enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase
      (DOHH). The crucial molecular function of eIF5A during translation has been
      recently elucidated in yeast and it is expected to be fully conserved in every
      eukaryotic cell, however the functional description of this pathway in plants is
      still sparse. The genetic approaches with transgenic plants for either eIF5A
      overexpression or antisense have revealed some activities related to the control
      of cell death processes but the molecular details remain to be characterized. One
      important aspect of fully understanding this pathway is the biochemical
      description of the hypusine modification system. Here we have used recombinant
      eIF5A proteins either modified by hypusination or non-modified to establish a bi
      dimensional electrophoresis (2D-E) profile for the three eIF5A protein isoforms
      and their hypusinated or unmodified proteoforms present in Arabidopsis thaliana.
      The combined use of the recombinant 2D-E profile together with 2D-E/western blot
      analysis from whole plant extracts has provided a quantitative approach to
      measure the hypusination status of eIF5A. We have used this information to
      demonstrate that treatment with the hormone abscisic acid produces an alteration
      of the hypusine modification system in Arabidopsis thaliana. Overall this study
      presents the first biochemical description of the post-translational modification
      of eIF5A by hypusination which will be functionally relevant for future studies
      related to the characterization of this pathway in Arabidopsis thaliana. 

PMID- 24904604
TI  - Transcriptional and biochemical responses of monoacylglycerol acyltransferase
      mediated oil synthesis and associated senescence-like responses in Nicotiana
      benthamiana.
AB  - Triacylglycerol (TAG) accumulates in plant seeds as a major renewable source of
      carbon for food, fuel and industrial feedstock. Approaches to enhance TAG content
      by altering lipid pathways and genes in vegetative parts have gained significant
      attention for biofuel and other applications. However, consequences of these
      modifications are not always studied in detail. In an attempt to increase TAG
      levels in leaves we previously demonstrated that a novel substrate,
      monoacylglycerol (MAG), can be used for the biosynthesis of diacylglycerol (DAG)
      and TAG. Transient expression of the Mus musculus monoacylglycerol
      acyltransferases MGAT1 and 2 in the model plant Nicotiana benthamiana increased
      TAG levels at 5 days post-infiltration (dpi). Here we show that increased TAG and
      DAG levels can be achieved as early as 2 dpi. In addition, the MGAT1 infiltrated
      areas showed senescence-like symptoms from 3 dpi onwards. To unravel underlying
      molecular mechanisms, Illumina deep sequencing was carried out (a) for de-novo
      assembling and annotation of N. benthamiana leaf transcripts and (b) to
      characterize MGAT1-responsive transcriptome. We found that MGAT1-responsive genes
      are involved in several processes including TAG biosynthesis, photosynthesis,
      cell-wall, cutin, suberin, wax and mucilage biosynthesis, lipid and hormone
      metabolism. Comparative analysis with transcript profiles from other senescence
      studies identified characteristic gene expression changes involved in senescence
      induction. We confirmed that increased TAG and observed senescence-symptoms are
      due to the MAG depletion caused by MGAT1 activity and suggest a mechanism for
      MGAT1 induced TAG increase and senescence-like symptoms. The data generated will
      serve as a valuable resource for oil and senescence related studies and for
      future N. benthamiana transcriptome studies. 

PMID- 24904605
TI  - Impacts of environmental factors on fine root lifespan.
AB  - The lifespan of fast-cycling roots is a critical parameter determining a large
      flux of plant carbon into soil through root turnover and is a biological feature
      regulating the capacity of a plant to capture soil water and nutrients via root
      age-related physiological processes. While the importance of root lifespan to
      whole-plant and ecosystem processes is increasingly recognized, robust
      descriptions of this dynamic process and its response to changes in climatic and
      edaphic factors are lacking. Here we synthesize available information and propose
      testable hypotheses using conceptual models to describe how changes in
      temperature, water, nitrogen (N), and phosphorus (P) availability impact fine
      root lifespan within a species. Each model is based on intrinsic responses
      including root physiological activity and alteration of carbohydrate allocation
      at the whole-plant level as well as extrinsic factors including mycorrhizal fungi
      and pressure from pathogens, herbivores, and other microbes. Simplifying
      interactions among these factors, we propose three general principles describing
      fine root responses to complex environmental gradients. First, increases in a
      factor that strongly constrains plant growth (temperature, water, N, or P) should
      result in increased fine root lifespan. Second, increases in a factor that
      exceeds plant demand or tolerance should result in decreased lifespan. Third, as
      multiple factors interact fine root responses should be determined by the most
      dominant factor controlling plant growth. Moving forward, field experiments
      should determine which types of species (e.g., coarse vs. fine rooted, obligate
      vs. facultative mycotrophs) will express greater plasticity in response to
      environmental gradients while ecosystem models may begin to incorporate more
      detailed descriptions of root lifespan and turnover. Together these efforts will
      improve quantitative understanding of root dynamics and help to identify areas
      where future research should be focused. 

PMID- 24904606
TI  - Genomic stability in response to high versus low linear energy transfer radiation
      in Arabidopsis thaliana.
AB  - Low linear energy transfer (LET) gamma rays and high LET HZE (high atomic weight,
      high energy) particles act as powerful mutagens in both plants and animals. DNA
      damage generated by HZE particles is more densely clustered than that generated
      by gamma rays. To understand the genetic requirements for resistance to high
      versus low LET radiation, a series of Arabidopsis thaliana mutants were exposed
      to either 1GeV Fe nuclei or gamma radiation. A comparison of effects on the
      germination and subsequent growth of seedlings led us to conclude that the
      relative biological effectiveness (RBE) of the two types of radiation (HZE versus
      gamma) are roughly 3:1. Similarly, in wild-type lines, loss of somatic
      heterozygosity was induced at an RBE of about a 2:1 (HZE versus gamma).
      Checkpoint and repair defects, as expected, enhanced sensitivity to both agents.
      The "replication fork" checkpoint, governed by ATR, played a slightly more
      important role in resistance to HZE-induced mutagenesis than in resistance to
      gamma induced mutagenesis. 

PMID- 24904608
TI  - The effect of NGATHA altered activity on auxin signaling pathways within the
      Arabidopsis gynoecium.
AB  - The four NGATHA genes (NGA) form a small subfamily within the large family of B3
      domain transcription factors of Arabidopsis thaliana. NGA genes act redundantly
      to direct the development of the apical tissues of the gynoecium, the style, and
      the stigma. Previous studies indicate that NGA genes could exert this function at
      least partially by directing the synthesis of auxin at the distal end of the
      developing gynoecium through the upregulation of two different YUCCA genes, which
      encode flavin monooxygenases involved in auxin biosynthesis. We have compared
      three developing pistil transcriptome data sets from wildtype, nga quadruple
      mutants, and a 35S::NGA3 line. The differentially expressed genes showed a
      significant enrichment for auxin-related genes, supporting the idea of NGA genes
      as major regulators of auxin accumulation and distribution within the developing
      gynoecium. We have introduced reporter lines for several of these differentially
      expressed genes involved in synthesis, transport and response to auxin in NGA
      gain- and loss-of-function backgrounds. We present here a detailed map of the
      response of these reporters to NGA misregulation that could help to clarify the
      role of NGA in auxin-mediated gynoecium morphogenesis. Our data point to a very
      reduced auxin synthesis in the developing apical gynoecium of nga mutants, likely
      responsible for the lack of DR5rev::GFP reporter activity observed in these
      mutants. In addition, NGA altered activity affects the expression of protein
      kinases that regulate the cellular localization of auxin efflux regulators, and
      thus likely impact auxin transport. Finally, protein accumulation in pistils of
      several ARFs was differentially affected by nga mutations or NGA overexpression,
      suggesting that these accumulation patterns depend not only on auxin distribution
      but could be also regulated by transcriptional networks involving NGA factors. 

PMID- 24904609
TI  - A phylogenetic approach to study the origin and evolution of plasmodesmata
      localized glycosyl hydrolases family 17.
AB  - Colonization of the land by plants required major modifications in cellular
      structural composition and metabolism. Intercellular communication through
      plasmodesmata (PD) plays a critical role in the coordination of growth and cell
      activities. Changes in the form, regulation or function of these channels are
      likely linked to plant adaptation to the terrestrial environments. Constriction
      of PD aperture by deposition of callose is the best-studied mechanism in PD
      regulation. Glycosyl hydrolases family 17 (GHL17) are callose degrading enzymes.
      In Arabidopsis this is a large protein family, few of which have been PD
      localized. The objective here is to identify correlations between evolution of
      this protein family and their role at PD and to use this information as a tool to
      predict the localization of candidates isolated in a proteomic screen. With this
      aim, we studied phylogenetic relationship between Arabidopsis GHL17 sequences and
      those isolated from fungi, green algae, mosses and monocot representatives. Three
      distinct phylogenetic clades were identified. Clade alpha contained only
      embryophytes sequences suggesting that this subgroup appeared during land
      colonization in organisms with functional PD. Accordingly, all PD-associated
      GHL17 proteins identified so far in Arabidopsis thaliana and Populus are grouped
      in this 'embryophytes only' phylogenetic clade. Next, we tested the use of this
      knowledge to discriminate between candidates isolated in the PD proteome.
      Transient and stable expression of GFP protein fusions confirmed PD localization
      for candidates contained in clade alpha but not for candidates contained in clade
      beta. Our results suggest that GHL17 membrane proteins contained in the alpha
      clade evolved and expanded during land colonization to play new roles, among
      others, in PD regulation. 

PMID- 24904610
TI  - Comparative transcriptome analysis of the metal hyperaccumulator Noccaea
      caerulescens.
AB  - The metal hyperaccumulator Noccaea caerulescens is an established model to study
      the adaptation of plants to metalliferous soils. Various comparators have been
      used in these studies. The choice of suitable comparators is important and
      depends on the hypothesis to be tested and methods to be used. In high-throughput
      analyses such as microarray, N. caerulescens has been compared to non-tolerant,
      non-accumulator plants like Arabidopsis thaliana or Thlaspi arvense rather than
      to the related hypertolerant or hyperaccumulator plants. An underutilized source
      is N. caerulescens populations with considerable variation in their capacity to
      accumulate and tolerate metals. Whole transcriptome sequencing (RNA-Seq) is
      revealing interesting variation in their gene expression profiles. Combining
      physiological characteristics of N. caerulescens accessions with their RNA-Seq
      has a great potential to provide detailed insight into the underlying molecular
      mechanisms, including entirely new gene products. In this review we will
      critically consider comparative transcriptome analyses carried out to explore
      metal hyperaccumulation and hypertolerance of N. caerulescens, and demonstrate
      the potential of RNA-Seq analysis as a tool in evolutionary genomics. 

PMID- 24904611
TI  - Root systems biology.

PMID- 24904607
TI  - Enhancing crop resilience to combined abiotic and biotic stress through the
      dissection of physiological and molecular crosstalk.
AB  - Plants growing in their natural habitats are often challenged simultaneously by
      multiple stress factors, both abiotic and biotic. Research has so far been
      limited to responses to individual stresses, and understanding of adaptation to
      combinatorial stress is limited, but indicative of non-additive interactions.
      Omics data analysis and functional characterization of individual genes has
      revealed a convergence of signaling pathways for abiotic and biotic stress
      adaptation. Taking into account that most data originate from imposition of
      individual stress factors, this review summarizes these findings in a
      physiological context, following the pathogenesis timeline and highlighting
      potential differential interactions occurring between abiotic and biotic stress
      signaling across the different cellular compartments and at the whole plant
      level. Potential effects of abiotic stress on resistance components such as
      extracellular receptor proteins, R-genes and systemic acquired resistance will be
      elaborated, as well as crosstalk at the levels of hormone, reactive oxygen
      species, and redox signaling. Breeding targets and strategies are proposed
      focusing on either manipulation and deployment of individual common regulators
      such as transcription factors or pyramiding of non- (negatively) interacting
      components such as R-genes with abiotic stress resistance genes. We propose that
      dissection of broad spectrum stress tolerance conferred by priming chemicals may
      provide an insight on stress cross regulation and additional candidate genes for
      improving crop performance under combined stress. Validation of the proposed
      strategies in lab and field experiments is a first step toward the goal of
      achieving tolerance to combinatorial stress in crops. 

PMID- 24904613
TI  - Genetic architecture of main effect QTL for heading date in European winter
      wheat.
AB  - A genome-wide association study (GWAS) for heading date (HD) was performed with a
      panel of 358 European winter wheat (Triticum aestivum L.) varieties and 14 spring
      wheat varieties through the phenotypic evaluation of HD in field tests in eight
      environments. Genotyping data consisted of 770 mapped microsatellite loci and
      7934 mapped SNP markers derived from the 90K iSelect wheat chip. Best linear
      unbiased estimations (BLUEs) were calculated across all trials and ranged from
      142.5 to 159.6 days after the 1st of January with an average value of 151.4 days.
      Considering only associations with a -log10 (P-value) >= 3.0, a total of 340 SSR
      and 2983 SNP marker-trait associations (MTAs) were detected. After Bonferroni
      correction for multiple testing, a total of 72 SSR and 438 SNP marker-trait
      associations remained significant. Highly significant MTAs were detected for the
      photoperiodism gene Ppd-D1, which was genotyped in all varieties. Consistent
      associations were found on all chromosomes with the highest number of MTAs on
      chromosome 5B. Linear regression showed a clear dependence of the HD score BLUEs
      on the number of favorable alleles (decreasing HD) and unfavorable alleles
      (increasing HD) per variety meaning that genotypes with a higher number of
      favorable or a low number of unfavorable alleles showed lower HD and therefore
      flowered earlier. For the vernalization gene Vrn-A2 co-locating MTAs on
      chromosome 5A, as well as for the photoperiodism genes Ppd-A1 and Ppd-B1 on
      chromosomes 2A and 2B were detected. After the construction of an integrated map
      of the SSR and SNP markers and by exploiting the synteny to sequenced species,
      such as rice and Brachypodium distachyon, we were able to demonstrate that a
      marker locus on wheat chromosome 5BL with homology to the rice photoperiodism
      gene Hd6 played a significant role in the determination of the heading date in
      wheat. 

PMID- 24904614
TI  - ER network dynamics are differentially controlled by myosins XI-K, XI-C, XI-E, XI
      I, XI-1, and XI-2.
AB  - The endoplasmic reticulum (ER) of higher plants is a complex network of tubules
      and cisternae. Some of the tubules and cisternae are relatively persistent, while
      others are dynamically moving and remodeling through growth and shrinkage, cycles
      of tubule elongation and retraction, and cisternal expansion and diminution.
      Previous work showed that transient expression in tobacco leaves of the motor
      less, truncated tail of myosin XI-K increases the relative area of both
      persistent cisternae and tubules in the ER. Likewise, transient expression of XI
      K tail diminishes the movement of organelles such as Golgi and peroxisomes. To
      examine whether other class XI myosins are involved in the remodeling and
      movement of the ER, other myosin XIs implicated in organelle movement, XI-1
      (MYA1),XI-2 (MYA2), XI-C, XI-E, XI-I, and one not, XI-A, were expressed as motor
      less tail constructs and their effect on ER persistent structures determined.
      Here, we indicate a differential effect on ER dynamics whereby certain class XI
      myosins may have more influence over controlling cisternalization rather than
      tubulation. 

PMID- 24904612
TI  - Analysis of plant microbe interactions in the era of next generation sequencing
      technologies.
AB  - Next generation sequencing (NGS) technologies have impressively accelerated
      research in biological science during the last years by enabling the production
      of large volumes of sequence data to a drastically lower price per base, compared
      to traditional sequencing methods. The recent and ongoing developments in the
      field allow addressing research questions in plant-microbe biology that were not
      conceivable just a few years ago. The present review provides an overview of NGS
      technologies and their usefulness for the analysis of microorganisms that live in
      association with plants. Possible limitations of the different sequencing
      systems, in particular sources of errors and bias, are critically discussed and
      methods are disclosed that help to overcome these shortcomings. A focus will be
      on the application of NGS methods in metagenomic studies, including the analysis
      of microbial communities by amplicon sequencing, which can be considered as a
      targeted metagenomic approach. Different applications of NGS technologies are
      exemplified by selected research articles that address the biology of the plant
      associated microbiota to demonstrate the worth of the new methods. 

PMID- 24904615
TI  - Post-embryonic organogenesis and plant regeneration from tissues: two sides of
      the same coin?
AB  - Plants have extraordinary developmental plasticity as they continuously form
      organs during post-embryonic development. In addition they may regenerate organs
      upon in vitro hormonal induction. Advances in the field of plant regeneration
      show that the first steps of de novo organogenesis through in vitro culture in
      hormone containing media (via formation of a proliferating mass of cells or
      callus) require root post-embryonic developmental programs as well as regulators
      of auxin and cytokinin signaling pathways. We review how hormonal regulation is
      delivered during lateral root initiation and callus formation. Implications in
      reprograming, cell fate and pluripotency acquisition are discussed. Finally, we
      analyze the function of cell cycle regulators and connections with epigenetic
      regulation. Future work dissecting plant organogenesis driven by both endogenous
      and exogenous cues (upon hormonal induction) may reveal new paradigms of common
      regulation. 

PMID- 24904616
TI  - Putative sugarcane FT/TFL1 genes delay flowering time and alter reproductive
      architecture in Arabidopsis.
AB  - Agriculturally important grasses such as rice, maize, and sugarcane are
      evolutionarily distant from Arabidopsis, yet some components of the floral
      induction process are highly conserved. Flowering in sugarcane is an important
      factor that negatively affects cane yield and reduces sugar/ethanol production
      from this important perennial bioenergy crop. Comparative studies have
      facilitated the identification and characterization of putative orthologs of key
      flowering time genes in sugarcane, a complex polyploid plant whose genome has yet
      to be sequenced completely. Using this approach we identified
      phosphatidylethanolamine-binding protein (PEBP) gene family members in sugarcane
      that are similar to the archetypical FT and TFL1 genes of Arabidopsis that play
      an essential role in controlling the transition from vegetative to reproductive
      growth. Expression analysis of ScTFL1, which falls into the TFL1-clade of floral
      repressors, showed transcripts in developing leaves surrounding the shoot apex
      but not at the apex itself. ScFT1 was detected in immature leaves and apical
      regions of vegetatively growing plants and, after the floral transition,
      expression also occurred in mature leaves. Ectopic over-expression of ScTFL1 in
      Arabidopsis caused delayed flowering in Arabidopsis, as might be expected for a
      gene related to TFL1. In addition, lines with the latest flowering phenotype
      exhibited aerial rosette formation. Unexpectedly, over-expression of ScFT1, which
      has greatest similarity to the florigen-encoding FT, also caused a delay in
      flowering. This preliminary analysis of divergent sugarcane FT and TFL1 gene
      family members from Saccharum spp. suggests that their expression patterns and
      roles in the floral transition has diverged from the predicted role of similar
      PEBP family members. 

PMID- 24904617
TI  - Mitochondrial dynamics and the cell cycle.
AB  - Nuclear-mitochondrial (NM) communication impacts many aspects of plant
      development including vigor, sterility, and viability. Dynamic changes in
      mitochondrial number, shape, size, and cellular location takes place during the
      cell cycle possibly impacting the process itself and leading to distribution of
      this organelle into daughter cells. The genes that underlie these changes are
      beginning to be identified in model plants such as Arabidopsis. In animals
      disruption of the drp1 gene, a homolog to the plant drp3A and drp3B, delays
      mitochondrial division. This mutation results in increased aneuploidy due to
      chromosome mis-segregation. It remains to be discovered if a similar outcome is
      observed in plants. Alloplasmic lines provide an opportunity to understand the
      communication between the cytoplasmic organelles and the nucleus. Examples of
      studies in these lines, especially from the extensive collection in wheat, point
      to the role of mitochondria in chromosome movement, pollen fertility and other
      aspects of development. 

PMID- 24904618
TI  - Transcription regulation by CHD proteins to control plant development.
AB  - Chromodomain-Helicase-DNA (CHD)-binding proteins have been characterized in
      various species as important transcription regulators by their chromatin
      remodeling activity. However, in plant the function of these proteins has hardly
      been analyzed before except that Arabidopsis PIKLE and rice CHR729 are identified
      to play critical roles in the regulation of series of genes involved in
      developmental or stress responding process. In this review we focus on how plant
      CHD proteins regulate gene expression and the role of these proteins in
      controlling plant development and stress response. 

PMID- 24904620
TI  - Biogenesis of the oxidative phosphorylation machinery in plants. From gene
      expression to complex assembly.

PMID- 24904621
TI  - Plant responses to flooding.

PMID- 24904619
TI  - Physiological and genomic basis of mechanical-functional trade-off in plant
      vasculature.
AB  - Some areas in plant abiotic stress research are not frequently addressed by
      genomic and molecular tools. One such area is the cross reaction of gravitational
      force with upward capillary pull of water and the mechanical-functional trade-off
      in plant vasculature. Although frost, drought and flooding stress greatly impact
      these physiological processes and consequently plant performance, the genomic and
      molecular basis of such trade-off is only sporadically addressed and so is its
      adaptive value. Embolism resistance is an important multiple stress- opposition
      trait and do offer scopes for critical insight to unravel and modify the input of
      living cells in the process and their biotechnological intervention may be of
      great importance. Vascular plants employ different physiological strategies to
      cope with embolism and variation is observed across the kingdom. The genomic
      resources in this area have started to emerge and open up possibilities of
      synthesis, validation and utilization of the new knowledge-base. This review
      article assesses the research till date on this issue and discusses new
      possibilities for bridging physiology and genomics of a plant, and foresees its
      implementation in crop science. 

PMID- 24904622
TI  - What lies beyond the eye: the molecular mechanisms regulating tomato fruit weight
      and shape.
AB  - Domestication of fruit and vegetables resulted in a huge diversity of shapes and
      sizes of the produce. Selections that took place over thousands of years of
      alleles that increased fruit weight and altered shape for specific culinary uses
      provide a wealth of resources to study the molecular bases of this diversity.
      Tomato (Solanum lycopersicum) evolved from a wild ancestor (S. pimpinellifolium)
      bearing small and round edible fruit. Molecular genetic studies led to the
      identification of two genes selected for fruit weight: FW2.2 encoding a member of
      the Cell Number Regulator family; and FW3.2 encoding a P450 enzyme and the
      ortholog of KLUH. Four genes were identified that were selected for fruit shape:
      SUN encoding a member of the IQD family of calmodulin-binding proteins leading to
      fruit elongation; OVATE encoding a member of the OVATE family proteins involved
      in transcriptional repression leading to fruit elongation; LC encoding most
      likely the ortholog of WUSCHEL controlling meristem size and locule number; FAS
      encoding a member in the YABBY family controlling locule number leading to flat
      or oxheart shape. For this article, we will provide an overview of the putative
      function of the known genes, when during floral and fruit development they are
      hypothesized to act and their potential importance in regulating morphological
      diversity in other fruit and vegetable crops. 

PMID- 24904624
TI  - Ectomycorrhizal identification in environmental samples of tree roots by Fourier
      transform infrared (FTIR) spectroscopy.
AB  - Roots of forest trees are associated with various ectomycorrhizal (ECM) fungal
      species that are involved in nutrient exchange between host plant and the soil
      compartment. The identification of ECM fungi in small environmental samples is
      difficult. The present study tested the feasibility of attenuated total
      reflection Fourier-transform infrared (ATR-FTIR) spectroscopy followed by
      hierarchical cluster analysis (HCA) to discriminate in situ collected ECM fungal
      species. Root tips colonized by distinct ECM fungal species, i.e., Amanita
      rubescens, Cenococcum geophilum, Lactarius subdulcis, Russula ochroleuca, and
      Xerocomus pruinatus were collected in mono-specific beech (Fagus sylvatica) and
      mixed deciduous forests in different geographic areas to investigate the
      environmental variability of the ECM FTIR signatures. A clear HCA discrimination
      was obtained for ECM fungal species independent of individual provenance.
      Environmental variability neither limited the discrimination between fungal
      species nor provided sufficient resolution to discern species sub-clusters for
      different sites. However, the de-convoluted FTIR spectra contained site-related
      spectral information for fungi with wide nutrient ranges, but not for Lactarius
      subdulcis, a fungus residing only in the litter layer. Specific markers for
      distinct ECM were identified in spectral regions associated with carbohydrates
      (i.e., mannans), lipids, and secondary protein structures. The present results
      support that FTIR spectroscopy coupled with multivariate analysis is a reliable
      and fast method to identify ECM fungal species in minute environmental samples.
      Moreover, our data suggest that the FTIR spectral signatures contain information
      on physiological and functional traits of ECM fungi. 

PMID- 24904623
TI  - Plant cell wall dynamics and wall-related susceptibility in plant-pathogen
      interactions.
AB  - The cell wall is a dynamic structure that often determines the outcome of the
      interactions between plants and pathogens. It is a barrier that pathogens need to
      breach to colonize the plant tissue. While fungal necrotrophs extensively destroy
      the integrity of the cell wall through the combined action of degrading enzymes,
      biotrophic fungi require a more localized and controlled degradation of the cell
      wall in order to keep the host cells alive and utilize their feeding structures.
      Also bacteria and nematodes need to degrade the plant cell wall at a certain
      stage of their infection process, to obtain nutrients for their growth. Plants
      have developed a system for sensing pathogens and monitoring the cell wall
      integrity, upon which they activate defense responses that lead to a dynamic cell
      wall remodeling required to prevent the disease. Pathogens, on the other hand,
      may exploit the host cell wall metabolism to support the infection. We review
      here the strategies utilized by both plants and pathogens to prevail in the cell
      wall battleground. 

PMID- 24904625
TI  - Distinct evolutionary strategies in the GGPPS family from plants.
AB  - Multiple geranylgeranyl diphosphate synthases (GGPPS) for biosynthesis of
      geranylgeranyl diphosphate (GGPP) exist in plants. GGPP is produced in the
      isoprenoid pathway and is a central precursor for various primary and specialized
      plant metabolites. Therefore, its biosynthesis is an essential regulatory point
      in the isoprenoid pathway. We selected 119 GGPPSs from 48 species representing
      all major plant lineages, based on stringent homology criteria. After the
      diversification of land plants, the number of GGPPS paralogs per species
      increases. Already in the moss Physcomitrella patens, GGPPS appears to be encoded
      by multiple paralogous genes. In gymnosperms, neofunctionalization of GGPPS may
      have enabled optimized biosynthesis of primary and specialized metabolites.
      Notably, lineage-specific expansion of GGPPS occurred in land plants. As a
      representative species we focused here on Arabidopsis thaliana, which retained
      the highest number of GGPPS paralogs (twelve) among the 48 species we considered
      in this study. Our results show that the A. thaliana GGPPS gene family is an
      example of evolution involving neo- and subfunctionalization as well as
      pseudogenization. We propose subfunctionalization as one of the main mechanisms
      allowing the maintenance of multiple GGPPS paralogs in A. thaliana genome.
      Accordingly, the changes in the expression patterns of the GGPPS paralogs
      occurring after gene duplication led to developmental and/or condition specific
      functional evolution. 

PMID- 24904626
TI  - Current challenges in photosynthesis: from natural to artificial.

PMID- 24904627
TI  - Seed dormancy and germination-emerging mechanisms and new hypotheses.
AB  - Seed dormancy has played a significant role in adaptation and evolution of seed
      plants. While its biological significance is clear, molecular mechanisms
      underlying seed dormancy induction, maintenance and alleviation still remain
      elusive. Intensive efforts have been made to investigate gibberellin and abscisic
      acid metabolism in seeds, which greatly contributed to the current understanding
      of seed dormancy mechanisms. Other mechanisms, which might be independent of
      hormones, or specific to the seed dormancy pathway, are also emerging from
      genetic analysis of "seed dormancy mutants." These studies suggest that chromatin
      remodeling through histone ubiquitination, methylation and acetylation, which
      could lead to transcription elongation or gene silencing, may play a significant
      role in seed dormancy regulation. Small interfering RNA and/or long non-coding
      RNA might be a trigger of epigenetic changes at the seed dormancy or germination
      loci, such as DELAY OF GERMINATION1. While new mechanisms are emerging from
      genetic studies of seed dormancy, novel hypotheses are also generated from seed
      germination studies with high throughput gene expression analysis. Recent studies
      on tissue-specific gene expression in tomato and Arabidopsis seeds, which
      suggested possible "mechanosensing" in the regulatory mechanisms, advanced our
      understanding of embryo-endosperm interaction and have potential to re-draw the
      traditional hypotheses or integrate them into a comprehensive scheme. The
      progress in basic seed science will enable knowledge translation, another
      frontier of research to be expanded for food and fuel production. 

PMID- 24904628
TI  - A new member of the psToc159 family contributes to distinct protein targeting
      pathways in pea chloroplasts.
AB  - Protein import into chloroplasts relies on specific targeting of preproteins from
      the cytosol to the organelles and coordinated translocation processes across the
      double envelope membrane. Here, two complex machineries constitute the so called
      general import pathway, which consists of the TOC and TIC complexes (translocon
      at the outer envelope of chloroplasts and translocon at the inner envelope of
      chloroplasts, respectively). The majority of canonical preproteins feature an N
      terminal cleavable transit peptide, which is necessary for targeting and
      recognition at the chloroplast surface by receptors of TOC, where Toc159 acts as
      the primary contact site. We identified a non-canonical preprotein without the
      classical transit peptide, the superoxide dismutase (FSD1), which was then used
      in chemical crosslinking approaches to find new interaction partners at the outer
      envelope from pea chloroplasts. In this way we could link FSD1 to members of the
      Toc159 family in pea, namely psToc132 and psToc120. Using deletion mutants as
      well as a peptide scanning approach we defined regions of the preprotein, which
      are involved in receptor binding. These are distributed across the entire
      sequence; however the extreme N-terminus as well as a C-proximal domain turned
      out to be essential for targeting and import. En route into the plastid FSD1
      engages components of the general import pathway, implying that in spite of the
      non-canonical targeting information and recognition by a specific receptor this
      preprotein follows a similar way across the envelope as the majority of plastid
      preproteins. 

PMID- 24904629
TI  - Control of foliar pathogens of spring barley using a combination of resistance
      elicitors.
AB  - The ability of the resistance elicitors acibenzolar-S-methyl (ASM), beta
      aminobutyric acid (BABA), cis-jasmone (CJ), and a combination of the three
      products, to control infection of spring barley by Rhynchosporium commune was
      examined under glasshouse conditions. Significant control of R. commune was
      provided by ASM and CJ, but the largest reduction in infection was obtained with
      the combination of the three elicitors. This elicitor combination was found to up
      regulate the expression of PR-1b, which is used as a molecular marker for
      systemic acquired resistance (SAR). However, the elicitor combination also down
      regulated the expression of LOX2, a gene involved in the biosynthesis of jasmonic
      acid (JA). In field experiments over 3 consecutive years, the effects of the
      elicitor combination were influenced greatly by crop variety and by year. For
      example, the elicitor combination applied on its own provided significant control
      of powdery mildew (Blumeria graminis f.sp. hordei) and R. commune in 2009,
      whereas no control on either variety was observed in 2007. In contrast,
      treatments involving both the elicitor combination and fungicides provided
      disease control and yield increases which were equal to, and in some cases better
      than that provided by the best fungicide-only treatment. The prospects for the
      use of elicitor plus fungicide treatments to control foliar pathogens of spring
      barley in practice are discussed. 

PMID- 24904630
TI  - Functional evaluation of DNA repair in human biopsies and their relation to other
      cellular biomarkers.
AB  - Thousands of DNA lesions are estimated to occur in each cell every day and almost
      all are recognized and repaired. DNA repair is an essential system that prevents
      accumulation of mutations which can lead to serious cellular malfunctions.
      Phenotypic evaluation of DNA repair activity of individuals is a relatively new
      approach. Methods to assess base and nucleotide excision repair pathways (BER and
      NER) in peripheral blood cells based on modified comet assay protocols have been
      widely applied in human epidemiological studies. These provided some interesting
      observations of individual DNA repair activity being suppressed among cancer
      patients. However, extension of these results to cancer target tissues requires a
      different approach. Here we describe the evaluation of BER and NER activities in
      extracts from deep-frozen colon biopsies using an upgraded version of the in
      vitro comet-based DNA repair assay in which 12 reactions on one microscope slide
      can be performed. The aim of this report is to provide a detailed, easy-to-follow
      protocol together with results of optimization experiments. Additionally, results
      obtained by functional assays were analyzed in the context of other cellular
      biomarkers, namely single nucleotide polymorphisms and gene expressions. We have
      shown that measuring DNA repair activity is not easily replaceable by genomic or
      transcriptomic approaches, but should be applied with the latter techniques in a
      complementary manner. The ability to measure DNA repair directly in cancer target
      tissues might finally answer questions about the tissue-specificity of DNA repair
      processes and their real involvement in the process of carcinogenesis. 

PMID- 24904631
TI  - Heterologous expression in Caenorhabditis elegans as an alternative approach to
      functional studies in Schistosoma mansoni.

PMID- 24904632
TI  - Network Assessor: an automated method for quantitative assessment of a network's
      potential for gene function prediction.
AB  - Significant effort has been invested in network-based gene function prediction
      algorithms based on the guilt by association (GBA) principle. Existing approaches
      for assessing prediction performance typically compute evaluation metrics, either
      averaged across all functions being considered, or strictly from properties of
      the network. Since the success of GBA algorithms depends on the specific function
      being predicted, evaluation metrics should instead be computed for each function.
      We describe a novel method for computing the usefulness of a network by measuring
      its impact on gene function cross validation prediction performance across all
      gene functions. We have implemented this in software called Network Assessor, and
      describe its use in the GeneMANIA (GM) quality control system. Network Assessor
      is part of the GM command line tools. 

PMID- 24904633
TI  - Adaptation through chromosomal inversions in Anopheles.
AB  - Chromosomal inversions have been repeatedly involved in local adaptation in a
      large number of animals and plants. The ecological and behavioral plasticity of
      Anopheles species-human malaria vectors-is mirrored by high amounts of
      polymorphic inversions. The adaptive significance of chromosomal inversions has
      been consistently attested by strong and significant correlations between their
      frequencies and a number of phenotypic traits. Here, we provide an extensive
      literature review of the different adaptive traits associated with chromosomal
      inversions in the genus Anopheles. Traits having important consequences for the
      success of present and future vector control measures, such as insecticide
      resistance and behavioral changes, are discussed. 

PMID- 24904634
TI  - Identification of potential therapeutic targets in a model of neuropathic pain.
AB  - Neuropathic pain (NP) is caused by damage to the nervous system, resulting in
      dysfunction and aberrant pain. The cellular functions (e.g., peripheral neuron
      spinal cord innervation, neuronal excitability) associated with NP often develop
      over time and are likely associated with gene expression changes. Gene expression
      studies on the cells involved in NP (e.g., sensory dorsal root ganglion neurons)
      are publically available; the mining of these studies may enable the
      identification of novel targets and the subsequent development of therapies that
      are essential for improving quality of life for the millions of individuals
      suffering with NP. Here we analyzed a publically available microarray dataset
      (GSE30165) in order to identify new RNAs (e.g., messenger RNA (mRNA) isoforms and
      non-coding RNAs) underlying NP. GSE30165 profiled gene expression in dorsal root
      ganglion neurons (DRG) and in sciatic nerve (SN) after resection, a NP model.
      Gene ontological analysis shows enrichment for sensory and neuronal processes.
      Protein network analysis demonstrates DRG upregulated genes typical to an injury
      and NP response. Of the top changing genes, 34 and 36% are associated with more
      than one protein coding isoform in the DRG and SN, respectively. The majority of
      genes are receptor and enzymes. We identified 15 long non-coding RNAs (lncRNAs)
      targeting these genes in LNCipedia.org, an online comprehensive lncRNA database.
      These RNAs represent new therapeutic targets for preventing NP development and
      this approach demonstrates the feasibility of data reanalysis for their
      identification. 

PMID- 24904635
TI  - Genome-wide association mapping including phenotypes from relatives without
      genotypes in a single-step (ssGWAS) for 6-week body weight in broiler chickens.
AB  - The purpose of this study was to compare results obtained from various
      methodologies for genome-wide association studies, when applied to real data, in
      terms of number and commonality of regions identified and their genetic variance
      explained, computational speed, and possible pitfalls in interpretations of
      results. Methodologies include: two iteratively reweighted single-step genomic
      BLUP procedures (ssGWAS1 and ssGWAS2), a single-marker model (CGWAS), and BayesB.
      The ssGWAS methods utilize genomic breeding values (GEBVs) based on combined
      pedigree, genomic and phenotypic information, while CGWAS and BayesB only utilize
      phenotypes from genotyped animals or pseudo-phenotypes. In this study, ssGWAS was
      performed by converting GEBVs to SNP marker effects. Unequal variances for
      markers were incorporated for calculating weights into a new genomic relationship
      matrix. SNP weights were refined iteratively. The data was body weight at 6 weeks
      on 274,776 broiler chickens, of which 4553 were genotyped using a 60 k SNP chip.
      Comparison of genomic regions was based on genetic variances explained by local
      SNP regions (20 SNPs). After 3 iterations, the noise was greatly reduced for
      ssGWAS1 and results are similar to that of CGWAS, with 4 out of the top 10
      regions in common. In contrast, for BayesB, the plot was dominated by a single
      region explaining 23.1% of the genetic variance. This same region was found by
      ssGWAS1 with the same rank, but the amount of genetic variation attributed to the
      region was only 3%. These findings emphasize the need for caution when comparing
      and interpreting results from various methods, and highlight that detected
      associations, and strength of association, strongly depends on methodologies and
      details of implementations. BayesB appears to overly shrink regions to zero,
      while overestimating the amount of genetic variation attributed to the remaining
      SNP effects. The real world is most likely a compromise between methods and
      remains to be determined. 

PMID- 24904636
TI  - Novel roles of the multi-functional CCR4-NOT complex in post-transcriptional
      regulation.
AB  - The CCR4-NOT complex is a highly conserved specific gene silencer that also
      serves more general post-transcriptional functions. Specific regulatory proteins
      including the miRNA-induced silencing complex and its associated proteins, bind
      to 3'-UTR elements of mRNA and recruit the CCR4-NOT complex thereby promoting
      poly(A) shortening and repressing translation and/or mRNA degradation. Recent
      studies have shown that the CCR4-NOT complex that is tethered to mRNA by such
      regulator(s) represses translation and facilitates mRNA decay independent of a
      poly(A) tail and its shortening. In addition to deadenylase activity, the CCR4
      NOT complex also has an E3 ubiquitin ligase activity and is involved in a novel
      protein quality control system, i.e., co-translational proteasomal-degradation of
      aberrant proteins. In this review, we describe recent progress in elucidation of
      novel roles of the multi-functional complex CCR4-NOT in post-transcriptional
      regulation. 

PMID- 24904637
TI  - Insights into the structure and architecture of the CCR4-NOT complex.
AB  - The CCR4-NOT complex is a highly conserved, multifunctional machinery with a
      general role in controlling mRNA metabolism. It has been implicated in a number
      of different aspects of mRNA and protein expression, including mRNA degradation,
      transcription initiation and elongation, ubiquitination, and protein
      modification. The core CCR4-NOT complex is evolutionarily conserved and consists
      of at least three NOT proteins and two catalytic subunits. The L-shaped complex
      is characterized by two functional modules bound to the CNOT1/Not1 scaffold
      protein: the deadenylase or nuclease module containing two enzymes required for
      deadenylation, and the NOT module. In this review, we will summarize the
      currently available information regarding the three-dimensional structure and
      assembly of the CCR4-NOT complex, in order to provide insight into its roles in
      mRNA degradation and other biological processes. 

PMID- 24904638
TI  - Beyond fossil calibrations: realities of molecular clock practices in
      evolutionary biology.
AB  - Molecular-based divergence dating methods, or molecular clocks, are the primary
      neontological tool for estimating the temporal origins of clades. While the
      appropriate use of vertebrate fossils as external clock calibrations has
      stimulated heated discussions in the paleontological community, less attention
      has been given to the quality and implementation of other calibration types. In
      lieu of appropriate fossils, many studies rely on alternative sources of age
      constraints based on geological events, substitution rates and heterochronous
      sampling, as well as dates secondarily derived from previous analyses. To
      illustrate the breadth and frequency of calibration types currently employed, we
      conducted a literature survey of over 600 articles published from 2007 to 2013.
      Over half of all analyses implemented one or more fossil dates as constraints,
      followed by geological events and secondary calibrations (15% each). Vertebrate
      taxa were subjects in nearly half of all studies, while invertebrates and plants
      together accounted for 43%, followed by viruses, protists and fungi (3% each).
      Current patterns in calibration practices were disproportionate to the number of
      discussions on their proper use, particularly regarding plants and secondarily
      derived dates, which are both relatively neglected in methodological evaluations.
      Based on our survey, we provide a comprehensive overview of the latest approaches
      in clock calibration, and outline strengths and weaknesses associated with each.
      This critique should serve as a call to action for researchers across multiple
      communities, particularly those working on clades for which fossil records are
      poor, to develop their own guidelines regarding selection and implementation of
      alternative calibration types. This issue is particularly relevant now, as time
      calibrated phylogenies are used for more than dating evolutionary origins, but
      often serve as the backbone of investigations into biogeography, diversity
      dynamics and rates of phenotypic evolution. 

PMID- 24904639
TI  - Identification of developmentally-specific kinotypes and mechanisms of Varroa
      mite resistance through whole-organism, kinome analysis of honeybee.
AB  - Recent investigations associate Varroa destructor (Mesostigmata: Varroidae)
      parasitism and its associated pathogens and agricultural pesticides with negative
      effects on colony health, resulting in sporadic global declines in domestic
      honeybee (Apis mellifera) populations. These events have motivated efforts to
      develop research tools that can offer insight into the causes of declining bee
      health as well as identify biomarkers to guide breeding programs. Here we report
      the development of a bee-specific peptide array for characterizing global
      cellular kinase activity in whole bee extracts. The arrays reveal distinct,
      developmentally-specific signaling profiles between bees with differential
      susceptibility to infestation by Varroa mites. Gene ontology analysis of the
      differentially phosphorylated peptides indicates that the differential
      susceptibility to Varroa mite infestation does not reflect compromised immunity;
      rather, there is evidence for mite-mediated immune suppression within the
      susceptible phenotype that may reduce the ability of these bees to counter
      secondary viral infections. This hypothesis is supported by the demonstration of
      more diverse viral infections in mite-infested, susceptible adult bees. The bee
      specific peptide arrays are an effective tool for understanding the molecular
      basis of this complex phenotype as well as for the discovery and utilization of
      phosphorylation biomarkers for breeding programs. 

PMID- 24904640
TI  - Redundancy of the genetic code enables translational pausing.
AB  - The codon redundancy ("degeneracy") found in protein-coding regions of mRNA also
      prescribes Translational Pausing (TP). When coupled with the appropriate
      interpreters, multiple meanings and functions are programmed into the same
      sequence of configurable switch-settings. This additional layer of Ontological
      Prescriptive Information (PIo) purposely slows or speeds up the translation
      decoding process within the ribosome. Variable translation rates help prescribe
      functional folding of the nascent protein. Redundancy of the codon to amino acid
      mapping, therefore, is anything but superfluous or degenerate. Redundancy
      programming allows for simultaneous dual prescriptions of TP and amino acid
      assignments without cross-talk. This allows both functions to be coincident and
      realizable. We will demonstrate that the TP schema is a bona fide rule-based
      code, conforming to logical code-like properties. Second, we will demonstrate
      that this TP code is programmed into the supposedly degenerate redundancy of the
      codon table. We will show that algorithmic processes play a dominant role in the
      realization of this multi-dimensional code. 

PMID- 24904641
TI  - The role of the E3 ligase Not4 in cotranslational quality control.
AB  - Cotranslational quality control (QC) is the mechanism by which the cell checks
      the integrity of newly synthesized proteins and mRNAs. In the event of mistakes
      these molecules are degraded. The Ccr4-Not complex has been proposed to play a
      role in this process. It contains both deadenylation and ubiquitination
      activities, thus it may target both aberrant proteins and mRNAs. Deadenylation is
      the first step in mRNA degradation. In yeast it is performed by the Ccr4 subunit
      of the Ccr4-Not complex. Another complex subunit, namely Not4, is a RING E3
      ligase and it provides the ubiquitination activity of the complex. It was found
      associated with translating ribosomes. Thus, it has been suggested that Not4 is
      involved in ribosome-associated ubiquitination and degradation of aberrant
      peptides. However, several other E3 ligases have been associated with peptide
      ubiquitination on the ribosome and the relevance of Not4 in this process remains
      unclear. In this review we summarize the recent data and suggest a role for Not4
      in cotranslational protein QC. 

PMID- 24904642
TI  - tRNA gene diversity in the three domains of life.
AB  - Transfer RNA (tRNA) is widely known for its key role in decoding mRNA into
      protein. Despite their necessity and relatively short nucleotide sequences, a
      large diversity of gene structures and RNA secondary structures of pre-tRNAs and
      mature tRNAs have recently been discovered in the three domains of life. Growing
      evidences of disrupted tRNA genes in the genomes of Archaea reveals unique gene
      structures such as, intron-containing tRNA, split tRNA, and permuted tRNA. Coding
      sequence for these tRNAs are either separated with introns, fragmented, or
      permuted at the genome level. Although evolutionary scenario behind the tRNA gene
      disruption is still unclear, diversity of tRNA structure seems to be co-evolved
      with their processing enzyme, so-called RNA splicing endonuclease. Metazoan
      mitochondrial tRNAs (mtRNAs) are known for their unique lack of either one or two
      arms from the typical tRNA cloverleaf structure, while still maintaining
      functionality. Recently identified nematode-specific V-arm containing tRNAs (nev
      tRNAs) possess long variable arms that are specific to eukaryotic class II
      tRNA(Ser) and tRNA(Leu) but also decode class I tRNA codons. Moreover, many tRNA
      like sequences have been found in the genomes of different organisms and viruses.
      Thus, this review is aimed to cover the latest knowledge on tRNA gene diversity
      and further recapitulate the evolutionary and biological aspects that caused such
      uniqueness. 

PMID- 24904643
TI  - Deadenylation of mRNA by the CCR4-NOT complex in Drosophila: molecular and
      developmental aspects.
AB  - Controlled shortening of the poly(A) tail of mRNAs is the first step in
      eukaryotic mRNA decay and can also be used for translational inactivation of
      mRNAs. The CCR4-NOT complex is the most important among a small number of
      deadenylases, enzymes catalyzing poly(A) tail shortening. Rates of poly(A)
      shortening differ between mRNAs as the CCR4-NOT complex is recruited to specific
      mRNAs by means of either sequence-specific RNA binding proteins or miRNAs. This
      review summarizes our current knowledge concerning the subunit composition and
      deadenylation activity of the Drosophila CCR4-NOT complex and the mechanisms by
      which the complex is recruited to particular mRNAs. We discuss genetic data
      implicating the complex in the regulation of specific mRNAs, in particular in the
      context of development. 

PMID- 24904646
TI  - Last-gen nostalgia: a lighthearted rant and reflection on genome sequencing
      culture.

PMID- 24904645
TI  - Glycans - the third revolution in evolution.
AB  - The development and maintenance of a complex organism composed of trillions of
      cells is an extremely complex task. At the molecular level every process requires
      a specific molecular structures to perform it, thus it is difficult to imagine
      how less than tenfold increase in the number of genes between simple bacteria and
      higher eukaryotes enabled this quantum leap in complexity. In this perspective
      article we present the hypothesis that the invention of glycans was the third
      revolution in evolution (the appearance of nucleic acids and proteins being the
      first two), which enabled the creation of novel molecular entities that do not
      require a direct genetic template. Contrary to proteins and nucleic acids, which
      are made from a direct DNA template, glycans are product of a complex
      biosynthetic pathway affected by hundreds of genetic and environmental factors.
      Therefore glycans enable adaptive response to environmental changes and, unlike
      other epiproteomic modifications, which act as off/on switches, glycosylation
      significantly contributes to protein structure and enables novel functions. The
      importance of glycosylation is evident from the fact that nearly all proteins
      invented after the appearance of multicellular life are composed of both
      polypeptide and glycan parts. 

PMID- 24904647
TI  - Homologous recombination is involved in the diversity of replacement flexible
      genomic islands in aquatic prokaryotes.
AB  - Different strains of the same prokaryotic species, even very similar ones, vary
      in large regions of their genomes. This flexible genome represents a huge
      reservoir of diversity that allows prokaryotes to exploit their environment
      efficiently. Most of the flexible genome is concentrated in genomic islands, some
      of which are present in all the strains and coding for similar functions but
      containing different genes. These replacement genomic islands are typically
      involved in exposed cellular structures, and their diversity has been connected
      to their recognition as targets by prokaryotic viruses (phages). We have compared
      genomes of closely related aquatic microbes from different origins and found
      examples of recent replacement of some of these flexible genomic islands. In all
      cases, that include Gram positive and negative bacteria and one archaeon, the
      replaced regions boundaries contain tell-tale peaks of increased, mostly
      synonymous, nucleotide substitutions. They tended to be sharper at the boundary
      closest to the origin of replication of the island. We will present the
      hypothesis that replacement flexible genomic islands are often exchanged by
      homologous recombination between different clonal frames. These recombination
      events are possibly selected due to the immediate reward provided by a change in
      the phage sensitivity spectrum. 

PMID- 24904648
TI  - In silico identification of genetic variants in glucocerebrosidase (GBA) gene
      involved in Gaucher's disease using multiple software tools.
AB  - Gaucher's 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.
      Polymorphisms in GBA gene have been associated with the development of Gaucher
      disease. We hypothesize that prediction of SNPs using multiple state of the art
      software tools will help in increasing the confidence in identification of SNPs
      involved in GD. Enzyme replacement therapy is the only option for GD. Our goal is
      to use several state of art SNP algorithms to predict/address harmful SNPs using
      comparative studies. In this study seven different algorithms (SIFT, MutPred,
      nsSNP Analyzer, PANTHER, PMUT, PROVEAN, and SNPs&GO) were used to predict the
      harmful polymorphisms. Among the seven programs, SIFT found 47 nsSNPs as
      deleterious, MutPred found 46 nsSNPs as harmful. nsSNP Analyzer program found 43
      out of 47 nsSNPs are disease causing SNPs whereas PANTHER found 32 out of 47 as
      highly deleterious, 22 out of 47 are classified as pathological mutations by
      PMUT, 44 out of 47 were predicted to be deleterious by PROVEAN server, all 47
      shows the disease related mutations by SNPs&GO. Twenty two nsSNPs were commonly
      predicted by all the seven different algorithms. The common 22 targeted mutations
      are F251L, C342G, W312C, P415R, R463C, D127V, A309V, G46E, G202E, P391L, Y363C,
      Y205C, W378C, I402T, S366R, F397S, Y418C, P401L, G195E, W184R, R48W, and T43R. 

PMID- 24904644
TI  - Methylated nucleosides in tRNA and tRNA methyltransferases.
AB  - To date, more than 90 modified nucleosides have been found in tRNA and the
      biosynthetic pathways of the majority of tRNA modifications include a methylation
      step(s). Recent studies of the biosynthetic pathways have demonstrated that the
      availability of methyl group donors for the methylation in tRNA is important for
      correct and efficient protein synthesis. In this review, I focus on the
      methylated nucleosides and tRNA methyltransferases. The primary functions of tRNA
      methylations are linked to the different steps of protein synthesis, such as the
      stabilization of tRNA structure, reinforcement of the codon-anticodon
      interaction, regulation of wobble base pairing, and prevention of frameshift
      errors. However, beyond these basic functions, recent studies have demonstrated
      that tRNA methylations are also involved in the RNA quality control system and
      regulation of tRNA localization in the cell. In a thermophilic eubacterium, tRNA
      modifications and the modification enzymes form a network that responses to
      temperature changes. Furthermore, several modifications are involved in genetic
      diseases, infections, and the immune response. Moreover, structural, biochemical,
      and bioinformatics studies of tRNA methyltransferases have been clarifying the
      details of tRNA methyltransferases and have enabled these enzymes to be
      classified. In the final section, the evolution of modification enzymes is
      discussed. 

PMID- 24904649
TI  - Different miRNA expression profiles between human breast cancer tumors and serum.
AB  - A bunch of microRNAs (miRNAs) have been demonstrated to be aberrantly expressed
      in cancer tumor tissue and serum. The miRNA signatures identified from the serum
      samples could serve as potential noninvasive diagnostic markers for breast
      cancer. The role of the miRNAs in cancerigenesis is unclear. In this study, we
      generated the expression profiles of miRNAs from the paired breast cancer tumors,
      normal, tissue, and serum samples from eight patients using small RNA-sequencing.
      Serum samples from eight healthy individuals were used as normal controls. We
      identified total 174 significantly differentially expressed miRNAs between tumors
      and the normal tissues, and 109 miRNAs between serum from patients and serum from
      healthy individuals. There are only 10 common miRNAs. This suggests that only a
      small portion of tumor miRNAs are released into serum selectively. Interestingly,
      the expression change pattern of 28 miRNAs is opposite between breast cancer
      tumors and serum. Functional analysis shows that the differentially expressed
      miRNAs and their target genes form a complex interaction network affecting many
      biological processes and involving in many types of cancer such as prostate
      cancer, basal cell carcinoma, acute myeloid leukemia, and more. 

PMID- 24904650
TI  - Quality control on the frontier.
AB  - In the world of high-throughput sequencing there are numerous challenges to
      effective data quality control. There are no single quality metrics which are
      appropriate in all conditions. Here we detail the different open source software
      used at the Exeter Sequencing Service to provide generic quality control
      information, as well as more specific metrics for genomic and transcriptomic
      libraries run on Illumina platforms. 

PMID- 24904651
TI  - Meta-analysis of randomized trials on access site selection for percutaneous
      coronary intervention in ST-segment elevation myocardial infarction.
AB  - INTRODUCTION: Superior outcomes with transradial (TRPCI) versus transfemoral
      coronary intervention (TFPCI) in the setting of acute ST-segment elevation
      myocardial infarction (STEMI) have been suggested by earlier studies. However,
      this effect was not evident in randomized controlled trials (RCTs), suggesting a
      possible allocation bias in observational studies. Since important studies with
      heterogeneous results regarding mortality have been published recently, we aimed
      to perform an updated review and meta-analysis on the safety and efficacy of
      TRPCI compared to TFPCI in the setting of STEMI. MATERIAL AND METHODS: Electronic
      databases were searched for relevant studies from January 1993 to November 2012.
      Outcome parameters of RCTs were pooled with the DerSimonian-Laird random-effects
      model. RESULTS: Twelve RCTs involving 5,124 patients were identified. According
      to the pooled analysis, TRPCI was associated with a significant reduction in
      major bleeding (odds ratio (OR): 0.52 (95% confidence interval (CI) 0.38-0.71, p
      < 0.0001)). The risk of mortality and major adverse events was significantly
      lower after TRPCI (OR = 0.58 (95% CI: 0.43-0.79), p = 0.0005 and OR = 0.67 (95%
      CI: 0.52-0.86), p = 0.002 respectively). CONCLUSIONS: Robust data from randomized
      clinical studies indicate that TRPCI reduces both ischemic and bleeding
      complications in STEMI. These findings support the preferential use of radial
      access for primary PCI.

PMID- 24904652
TI  - Second- versus first-generation drug-eluting stents for diabetic patients: a meta
      analysis.
AB  - INTRODUCTION: The issue of whether various drug-eluting stents (DES) provide
      similar benefit in diabetic patients with coronary artery disease remains
      unclear. The purpose of the study is to assess the clinical utility of the second
      generation and first-generation DES in patients with diabetes mellitus by a meta
      analysis. MATERIAL AND METHODS: A systematic literature search of PubMed, EMBASE,
      and Cochrane databases was conducted. We included randomized trials involving
      head-to-head comparison of clinical outcomes of second- versus first-generation
      DES in patients with a diagnosis of diabetes with at least 6-month follow-up
      data. Summary statistics were calculated using random-effects models. RESULTS: A
      total of 10 trials with 4503 patients were available for analysis. The pooled
      analyses showed that the second-generation everolimus-eluting stent (EES)
      significantly lowered all-cause mortality (risk ratio (RR) = 0.58, 95% CI: 0.37
      0.90; p = 0.01) and the risk of stent thrombosis (RR = 0.46, 95% CI: 0.22-0.95; p
      = 0.03) compared with the first-generation sirolimus-eluting stents (SES) and the
      overall first-generation DES, respectively. Moreover, the EES showed a tendency
      toward reducing the incidence of recurrent myocardial infarction when compared
      with paclitaxel-eluting stents (PES) (RR = 0.58, p = 0.08). In contrast, the
      second-generation zotarolimus-eluting stents (ZES) were associated with increased
      rates of stent thrombosis and risk of target lesion revascularization in
      comparison with the SES (both p < 0.05) or the overall first-generation DES (both
      p < 0.05). CONCLUSIONS: The second-generation EES are highly effective in
      reducing the risk of major cardiac events in diabetic patients with coronary
      artery disease.

PMID- 24904654
TI  - Detection and significance of TregFoxP3(+) and Th17 cells in peripheral blood of
      non-small cell lung cancer patients.
AB  - INTRODUCTION: The aim of this study was to explore the relationships between
      TregFoxP3(+) cells and Th17 cells and occurrence of lung cancer. MATERIAL AND
      METHODS: The proportions of TregFoxP3(+) and Th17 cells, the expression of FoxP3
      and RORgammat mRNA, and the levels of related cell factors such as transforming
      growth factor-beta (TGF-beta), interleukin IL-17 (IL-17) and IL-23 were
      determined respectively by flow cytometry analysis, real-time-polymerase chain
      reaction (PCR), and ELISA in peripheral blood of 18 healthy people and 26
      patients with non-small cell lung cancer (NSCLC). RESULTS: The levels of
      TregFoxP3(+) and Th17, expression of FoxP3 and RORgammat mRNA, and ratios of
      TregFoxP3(+)/Th17 and FoxP3/RORgammat in peripheral blood with NSCLC were higher
      than those in healthy controls (p < 0.05). The proportion of Th17 cells from
      NSCLC patients was positively correlated with that of TregFoxP3(+) (r = 0.81, p <
      0.05). The receiver-operating characteristic (ROC) curve demonstrates that the
      increased level of TregFoxP3(+)/Th17 in the peripheral blood may be a useful
      indicator in early diagnosis of non-small cell lung carcinoma. The
      TregFoxP3(+)/Th17 and FoxP3/RORgammat levels for patients in stage IV were higher
      than those of patients in stages I, II, and III (p < 0.05). The levels of TGF
      beta, IL-17, and IL-23 were higher in NSCLC patients than those in healthy
      controls. CONCLUSIONS: The results suggest that ratios of Treg/Th17 correlate
      with the stage of NSCLC.

PMID- 24904653
TI  - Positron emission tomography alone, positron emission tomography-computed
      tomography and computed tomography in diagnosing recurrent cervical carcinoma: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: The aim of the study was to assess systematically the accuracies of
      positron emission tomography (PET), PET/computed tomography (CT), and CT in
      diagnosing recurrent cervical cancer. MATERIAL AND METHODS: We searched for
      articles published from January 1980 to June 2013 using the following inclusion
      criteria: articles were reported in English; the use of PET, interpreted with or
      without the use of CT; use of CT to detect recurrent cervical cancer; and
      histopathologic analysis and/or close clinical and imaging follow-up for at least
      6 months. We extracted data to calculate sensitivity, specificity, summary
      receiver operating characteristic curves, and the area under the receiver
      operating characteristic curve (AUC) as well as test for heterogeneity. RESULTS:
      In 23 included studies, PET had the highest pooled specificity at 92% (95% CI: 90
      94), whereas PET/CT had the highest pooled sensitivity at 94% (95% CI: 90-97).
      The area under the curve (AUC) of PET alone, PET/CT, and CT were 0.9594, 0.9508,
      and 0.9363, respectively. Results of the pairwise comparison between each
      modality show that the specificity of PET was higher than that of PET/CT (p <
      0.05). The difference in the pooled sensitivities and AUC of PET alone and PET/CT
      showed no statistical significance. No evidence of publication bias was found.
      However, evidence of heterogeneity was observed. CONCLUSIONS: The PET/CT may be a
      useful supplement to current surveillance techniques, particularly for patients
      with negative CT imaging. However, in terms of diagnostic accuracy, interpreted
      CT images may have limited additional value to PET in detecting recurrent
      cervical cancer.

PMID- 24904655
TI  - Arg389Gly beta1-adrenergic receptor polymorphism and susceptibility to syncope
      during tilt test.
AB  - INTRODUCTION: Numerous hormones, neurotransmitters, and other stimuli exert their
      biological effect on cellular functioning through heptahelical receptors coupled
      to G proteins (GPCR - G protein-coupled receptors). Adrenergic receptors that
      belong to this superfamily of receptors are components of the sympathetic nervous
      system. They play a pivotal role in blood pressure regulation and myocardial
      contractility. Alterations of the adrenergic receptor pathway have been suggested
      to be involved in the pathophysiology of vasovagal syncope (VVS). The aim of the
      present study was to evaluate the distribution of Arg389Gly polymorphism within
      the ADRB1 gene among patients with recurrent syncope. MATERIAL AND METHODS:
      Arg389Gly single nucleotide polymorphism was analyzed in 205 patients with
      recurrent syncope. Ninety-five patients (46%) had a positive head-up tilt test
      (HUT) result. The control group comprised 143 non-fainting subjects. Genotyping
      was performed by restriction fragment length polymorphism (RFLP) with BstNI
      enzyme. RESULTS: Both analyzed groups had similar distribution of the 389Gly
      allele. Sixty percent of polymorphic 389Gly carriers belong to the group of
      syncopal patients, while 40% belong to the control group of healthy subjects.
      CONCLUSIONS: An association between syncopal incidence and Arg389Gly polymorphism
      within the ADRB1 gene was not found. The analyzed polymorphism affecting
      sympathetic activity does not influence vasovagal syncope in Polish patients.

PMID- 24904656
TI  - Effects of natural honey on polymicrobial culture of various human pathogens.
AB  - INTRODUCTION: Honey has a wide range of antimicrobial activity. All previous
      studies have considered honey's effect on a single microbe. The present study
      investigated activity of honey towards a high dose of single or polymicrobial
      culture. MATERIAL AND METHODS: 10 ul specimens of Staphylococcus aureus (S.
      aureus), Streptococcus pyogenes (S. pyogenes), Escherichia coli (E. coli) and
      Candida albicans (C. albicans) were cultured in 10 ml of 10-100% (wt/v) honey
      diluted in broth. Six types of polymicrobial microbial cultures were prepared by
      culturing the isolates with each other onto broth (control) and broth containing
      various concentrations of honey (10-100% wt/v). Microbial growth was assessed on
      solid plate media after 24 h incubation. RESULTS: Honey (30-70%) prevents growth
      of 10 ul specimens of all the isolates. Greater reduction in growth of E. coli
      was observed when cultured with S. aureus. Culturing of S. aureus with S.
      pyogenes, C. albicans, or E. coli increased its sensitivity to honey. S. aureus
      and S. pyogenes increased sensitivity of C. albicans to honey while E. coli and
      C. albicans decreased sensitivity of S. pyogenes. CONCLUSIONS: It might be
      concluded that honey prevents and inhibits growth of single and polymicrobial
      pathogenic cultures. Polymicrobial culture affects growth of the isolates and
      increases their sensitivity to honey.

PMID- 24904657
TI  - Hyperkalemia among hospitalized patients and association between duration of
      hyperkalemia and outcomes.
AB  - INTRODUCTION: The aim of the study was to investigate predictors of mortality in
      patients hospitalized with hyperkalemia. MATERIAL AND METHODS: Data among
      hospitalized patients with hyperkalemia (serum potassium >= 5.1 mEq/l) were
      collected. Patients with end-stage renal disease on dialysis were excluded.
      RESULTS: Of 15,608 hospitalizations, 451 (2.9%) episodes of hyperkalemia occurred
      in 408 patients. In patients with hyperkalemia, chronic kidney disease,
      hypertension, diabetes, coronary artery disease and heart failure were common
      comorbidities. Acute kidney injury (AKI) and metabolic acidosis were common
      metabolic abnormalities, and 359 patients (88%) were on at least one drug
      associated with hyperkalemia. Mean duration to resolution of hyperkalemia was 12
      +/-9.9 h. Nonsteroidal anti-inflammatory drugs (HR = 1.59), highest potassium
      level (HR = 0.61), tissue necrosis (HR = 0.61), metabolic acidosis (HR = 0.77),
      and AKI (HR = 0.77) were significant independent determinants of duration prior
      to hyperkalemia resolution. Tissue necrosis (OR = 4.55), potassium
      supplementation (OR = 5.46), metabolic acidosis (OR = 4.84), use of calcium
      gluconate for treatment of hyperkalemia (OR = 4.62), AKI (OR = 3.89), and
      prolonged duration of hyperkalemia (OR = 1.06) were significant independent
      predictors of in-hospital mortality. CONCLUSIONS: Tissue necrosis, potassium
      supplementation, metabolic acidosis, calcium gluconate for treatment of
      hyperkalemia, AKI and prolonged duration of hyperkalemia are independent
      predictors of in-hospital mortality.

PMID- 24904658
TI  - Endocardial Lead Extraction in the Polish Registry - clinical practice versus
      current Heart Rhythm Society consensus.
AB  - INTRODUCTION: Over the last 10 years, there has been an increasing number of
      patients with pacemaker (PM) and cardioverter-defibrillator (ICD). This study is
      a retrospective analysis of indications for endocardial pacemaker and ICD lead
      extractions between 2003 and 2009 based on the experience of three Polish
      Referral Lead Extraction Centers. MATERIAL AND METHODS: Since 2003, the authors
      have consecutively retrospectively collected all cases and entered the
      information in the database. All patients which had indication for lead
      extraction according to Heart Rhythm Society Guidelines were included to final
      analyze. Between 2003 and 2005, the data were analyzed together. Since 2006, data
      have been collected and analyzed annually. RESULTS: In each year, a significant
      increase in lead extraction was observed. The main indications for LE were
      infections in 52.4% of patients. Nonfunctioning lead extraction constituted the
      second group of indications for LE in 29.7% of patients. During the registry
      period, the percentage of class I indications decreased from 80% in 2006 to only
      47% in 2009. On the other hand, increasingly more leads were removed because of
      class 2, especially class 2b. In 2009, 40% of leads were extracted due to class
      2b. CONCLUSIONS: Polish Registry of Endocardial Lead Extraction 2003-2009, shows
      an increasing frequency of lead extraction. The main indication for LE is
      infection: systemic and pocket. An increase in class 2, especially 2b, LE
      indication in every center during the study period was found.

PMID- 24904659
TI  - Contact force mapping during catheter ablation for atrial fibrillation:
      procedural data and one-year follow-up.
AB  - INTRODUCTION: Pulmonary vein isolation (PVI) is the state-of-the-art treatment of
      atrial fibrillation (AF). Pulmonary vein reconnection is one of the main
      mechanisms of AF recurrence after ablation. Catheter-tissue contact is essential
      for effective ablation lesions. The aim of this study was to evaluate the impact
      of catheter contact monitoring during PVI on AF recurrence rate. MATERIAL AND
      METHODS: One hundred and forty-three patients who underwent PVI were analysed. In
      31 patients, PVI was performed by monitoring the catheter-tissue contact with a
      contact force (CF) sensing catheter. One hundred and twelve patients in whom
      conventional PVI was performed without CF information served as the control
      group. Procedural data and recurrence rate within 12-month follow-up were
      compared. RESULTS: A significant reduction in procedure duration was seen in the
      CF mapping group (128.4 +/-29 min vs. 157.7 +/-30.8 min, p = 0.001). Complete
      pulmonary vein isolation was achieved in 100% of the patients. Rate of AF
      recurrence within 12 months after ablation was significantly lower in the contact
      force group (16.1%) when compared to the standard ablation group (36.6%) (p =
      0.031). CONCLUSIONS: Pulmonary vein isolation with the use of contact force
      information results in a shorter procedure duration and a lower rate of AF
      recurrence after 12 months compared to conventional PVI without this information.
      Catheter-tissue contact monitoring may have a beneficial effect on mid-term and
      long-term results of PVI procedures.

PMID- 24904660
TI  - Abdominal aortic aneurysm repair: long-term follow-up of endovascular versus open
      repair.
AB  - INTRODUCTION: To compare early and long-term outcomes of endovascular abdominal
      aortic aneurysm repair (EVAR) versus open repair (OPEN). DESIGN: Prospective
      observational, per protocol, non-randomized, with retrospective analyses.
      MATERIAL AND METHODS: Between 2000 and 2005, a total of 311 patients having EVAR
      or OPEN repair of infrarenal abdominal aortic aneurysms were identified and
      included in this prospective single-center observational study. A propensity
      score-based optimal-matching algorithm was employed, and 138 patients undergoing
      EVAR procedures were matched (1: 1) to OPEN repair. RESULTS: Open repair showed
      higher hospital mortality (17% vs. 6%, p = 0.004), respiratory failure (p <
      0.026), transfusion requirement (p < 0.001), and intensive care unit admission
      (27% vs. 7%, p < 0.001), and longer hospitalization (p < 0.001). Median follow-up
      was 70 months (25(th) to 75(th) percentile, 24 to 101). Actuarial survival
      estimates at 1, 5 and 10 years were 93%, 74%, 49% for the OPEN group compared to
      89%, 69%, 59% for the EVAR group (p = 0.465). A significant difference between
      groups was observed in younger patients (< 75 years) only (p < 0.044). Late
      complication and re-intervention rates were significantly higher in EVAR patients
      (p < 0.001 and p = 0.002, respectively). Freedom from late complications at 1, 5
      and 10 years was 96%, 92%, 86%, and 84%, 70%, 64% for OPEN and EVAR procedures,
      respectively. CONCLUSIONS: Our experience confirms the excellent results of the
      EVAR procedures, offering excellent early and long-term results in terms of
      safety and reduction of mortality. Patients < 75 years seem to benefit from EVAR
      not only in the immediate postoperative period but even in a long-term
      perspective.

PMID- 24904661
TI  - Application of gentamicin-collagen sponge shortened wound healing time after
      minor amputations in diabetic patients - a prospective, randomised trial.
AB  - INTRODUCTION: Diabetic foot infections are frequently polymicrobial. The lower
      tissue concentration of systemically administered antibiotics in diabetic
      patients was reported. Collatamp((r))EG (Syntacoll GmbH Saal/Donau, Germany) is a
      bioabsorbable, gentamicin impregnated collagen spongeused for local treatment.
      The aim of this randomized trial was to assess influence of gentamicin-collagen
      sponge applied to a wound on surgical outcomes after minor amputations in
      diabetic patients. MATERIAL AND METHODS: Fifty diabetic patients indicated for
      minor amputation in 2009 at our surgery department were included in the study.
      Patients were pre-operatively randomised into two groups. Twenty-five patients in
      group A were treated with gentamicin impregnated collagen sponge applied into
      wound peri-operatively while 25 patients in group B had minor amputation without
      gentamicin sponge. RESULTS: There was no significant difference in the
      demographic data, procedures performed, diabetes duration and peripheral vascular
      disease severity between the groups. The median glycosylated haemoglobin was 6.0%
      (range: 4.6-9.5%) in group A and 6.2% (range: 4.0-8.4%) in control group B (non
      significant). Median TcPO2 level was 44 (range: 13-67) in group A and 48 (range:
      11-69) in control group B (non-significant). The median of wound healing duration
      in group A was 3.0 weeks (range: 1.7-17.1 weeks) compared to 4.9 weeks (range:
      2.6-20.0 weeks) in control group B. This was with a statistically significant
      difference (p < 0.05). CONCLUSIONS: Application of gentamicin impregnated
      collagen sponge shortened wound healing duration after minor amputations in
      diabetic patients by almost 2 weeks.

PMID- 24904662
TI  - Pancreatic head carcinoma and vascular endothelial growth factor (VEGF-A)
      concentration in portal blood: its association with cancer grade, tumor size and
      probably poor prognosis.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF) is overexpressed in
      pancreatic cancer. Although VEGF has been shown to be a probable marker for poor
      prognosis, the VEGF concentration in portal blood has not yet been clinically
      reported in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to
      measure VEGF-A portal blood concentration in patients with PDAC and to evaluate
      its performance as a prognostic marker. MATERIAL AND METHODS: Thirty-six
      consecutive patients out of 57 operated on for pancreatic head lesion with
      pathologically verified diagnosis of PDAC were enrolled in this study. We
      evaluated the VEGF concentration in portal blood samples obtained
      intraoperatively and associated their values with tumor size, stage, grade and
      survival. RESULTS: The portal VEGF-A concentration was associated with tumor
      grade (G1: 80.52 +/-43.05 vs. G2: 185.39 +/-134.98, p = 0.006, G2: 185.39 +/
      134.98 vs. G3: 356.46 +/-229.12, p = 0.08), and there was a positive correlation
      with tumor size (r = 0.42, p < 0.05). In the multivariate regression analysis
      high levels of VEGF-A were not correlated with poor survival (HR = 5.22, 95% CI =
      -0.6457 to 3.9513, p = 0.19). CONCLUSIONS: The portal VEGF-A concentration is
      associated with tumor grade and size. The correlation of portal VEGF-A with poor
      survival is not clear and needs further investigation.

PMID- 24904663
TI  - Assessment of the response to gluten-free diet in an Iraqi population with
      coeliac disease. A histological and serological follow-up study.
AB  - INTRODUCTION: Coeliac disease (CD) is a common diagnosis among children and
      adults in Iraq; however, removal of gluten from the diet is essential for
      patients with CD. The aim of this study, the first such study in Iraq, was to
      assess the serological and histological recovery profiles of coeliac patients, in
      both children and adults groups after commencing a gluten-free diet (GFD) for at
      least 1 year +/- 1 month. MATERIAL AND METHODS: The study group comprised 78
      proved coeliac patients (46 children and 32 adults, median age: 15 years, range:
      1-66 years) who all agreed to undergo endoscopy in addition to serological
      assessment before and after treatment. The duodenal biopsies were interpreted
      histologically according to modified Marsh criteria and the sera were tested for
      anti-gliadin antibody (AGA), endomysium antibody (EMA) and anti-tissue
      transglutaminase antibody (tTG). RESULTS: Complete histological remission was
      seen in 29 (63.1%) of 46 treated children CD patients, while only 5 (10.9%)
      showed Marsh IIIa changes compared with 11 (24%) before GFD. Similarly none of
      the 32 adults after GFD showed Marsh IIIb and Marsh IIIc compared with 46.9% and
      28.1% before treatment respectively (p = 001). Meanwhile, there was strongly
      significant reduction in AGA, EMA, and tTG antibodies levels (p = 0.00001)
      following GFD. CONCLUSIONS: Repeating the duodenal biopsy 1 year +/-1 month after
      diagnosis and starting a GFD supports the routine measurement of using
      histological findings as a gold standard test to confirm recovery of Iraqi CD
      patients along with using known coeliac serology antibodies.

PMID- 24904664
TI  - Intraoperative blood loss during surgical treatment of low-rectal cancer by
      abdominosacral resection is higher than during extra-levator abdominosacral
      amputation of the rectum.
AB  - INTRODUCTION: Abdominosacral resection (ASR) usually required blood transfusions,
      which are virtually no longer in use in the modified abdominosacral amputation of
      the rectum (ASAR). The aim of this study was to compare the intra-operative
      bleeding in low-rectal patients subjected to ASR or ASAR. MATERIAL AND METHODS:
      The study included low-rectal cancer patients subjected to ASR (n = 114) or ASAR
      (n = 46) who were retrospectively compared in terms of: 1) the frequency of blood
      transfusions during surgery and up to 24 h thereafter; 2) the volume of
      intraoperative blood loss (ml of blood transfused) during surgery and up to 24 h
      thereafter; 3) hemoglobin concentrations (Hb) 1, 3 and 5 days after surgery; 4)
      the duration of hospitalization. RESULTS: Blood transfusions were necessary in
      107 ASR patients but in none of those subjected to ASAR (p < 0.001). Median blood
      loss in the ASR group was 800 ml (range: 100-4500 ml). The differences between
      the groups in median Hb determined 1, 3 and 5 days following surgery were
      insignificant. The proportions of patients with abnormal values of Hb, however,
      were significantly higher in the ASR group on postoperative days 1 and 3 (day 1:
      71.9% vs. 19.6% in the ASAR group, p = 0.025; day 3: 57.% vs. 13.0%, p = 0.009).
      Average postoperative hospitalization in ASR patients was 13 days compared to 9
      days in the ASAR group (p = 0.031). CONCLUSIONS: Abdominosacral amputation of the
      rectum predominates over ASR in terms of the prevention of intra- and
      postoperative bleeding due to the properly defined surgical plane in low-rectal
      cancer patients.

PMID- 24904665
TI  - The hypotensive effect of selective laser trabeculoplasty depending on
      iridocorneal angle pigmentation in primary open angle glaucoma patients.
AB  - INTRODUCTION: Selective laser trabeculoplasty (SLT) is applied to reduce
      intraocular pressure in primary open angle glaucoma therapy. It selectively
      subjects trabecular pigmented cells to a pulsed, frequency-doubled Nd:YAG laser.
      The biostimulatory effect on trabecular macrophages was also postulated even in
      low-pigmented angles. The aim of the study was to assess the hypotensive
      effectiveness of SLT depending on the degree of iridocorneal angle pigmentation.
      MATERIAL AND METHODS: Sixty-three eyes of 53 patients with primary open angle
      glaucoma (POAG) were included in this study and than divided into three
      subgroups, dependind of iridocorneal angle pigmentation. All subjects underwent
      SLT on 270 degrees of the angle. Intraocular pressure (IOP) was assesed at
      baseline and 6 weeks after the laser procedure. RESULTS: Six weeks post-SLT mean
      IOP reduction was 2.63 mm Hg. The degree of IOP reduction showed a significant
      correlation with angle pigmentation. Intraocular pressure fell by 2.06 mm Hg,
      2.46 mm Hg and 4.75 mm Hg in subgroups with low, marked and high pigmentation,
      respectively. CONCLUSIONS: The SLT procedure most effectively reduces IOP only in
      the subgroup of POAG patients with marked angle pigmentation and it is equal to
      clinically succesfull hypontesive therapeutic effect, according to European
      Glaucoma Society guidelines. However, lower hypotensive effect in other study
      subjects may also be the valuable addition to pharmacological therapy of
      glaucoma.

PMID- 24904667
TI  - Comparison of the GenoType((r)) MTBC Molecular Genetic Assay with culture methods
      in the diagnosis of tuberculosis.
AB  - INTRODUCTION: Clinical samples from 433 patients pre-diagnosed with tuberculosis
      in Konya, Turkey, were investigated prospectively to compare the GenoType((r))
      MTBC test (GenoType((r)) MTBC) with conventional "gold standard" culture methods.
      MATERIAL AND METHODS: Lowenstein Jensen (LJ) and Mycobacteria Growth Indicator
      Tube (MGIT)-960 culture methods and GenoType((r)) MTBC were performed together.
      RESULTS: Mycobacterium tuberculosis (M. tuberculosis) detection rates were 16.2%
      by culture methods, 15.4% by GenoType((r)) MTBC, and 6% by acid-fast bacilli
      microscopy. The LJ or MGIT-960 with GenoType((r)) MTBC detected M. tuberculosis
      in 12 samples each that were negative according to the other culture method
      alone. Among 70 M. tuberculosis-positive samples, detection rates were 37%
      (26/70) by microscopy and 82.8% (58/70) by LJ and MGIT-960, but 95.7% (67/70) by
      GenoType((r)) MTBC. CONCLUSIONS: GenoType((r)) MTBC may be used as a beneficial
      adjunct test to culture methods for the detection of M. tuberculosis.

PMID- 24904666
TI  - Naloxone therapy in opioid overdose patients: intranasal or intravenous? A
      randomized clinical trial.
AB  - INTRODUCTION: This study was designed to compare the effects of intranasal (IN)
      and intravenous (IV) administration of naloxone in patients who had overdosed on
      opioids. MATERIAL AND METHODS: This randomized clinical trial study was conducted
      in the Department of Poisoning Emergencies at Noor and Ali Asghar (PBUH)
      University Hospital. One hundred opioid overdose patients were assigned by random
      allocation software into two study groups (n = 50). Both groups received 0.4 mg
      naloxone: one group IN and the other IV. Outcomes included change in the level of
      consciousness (measured using a descriptive scale and the Glasgow Coma Scale
      (GCS)), time to response, vital signs (blood pressure, heart rate and respiratory
      rate), arterial blood O2 saturation before and after naloxone administration,
      side-effects (agitation) and length of hospital stay. RESULTS: Patients who had
      been administered IN naloxone demonstrated significantly higher levels of
      consciousness than those in the IV group using both descriptive and GCS scales (p
      < 0.001). There was a significant difference in the heart rate between IN and IV
      groups (p = 0.003). However, blood pressure, respiratory rate and arterial O2
      saturation were not significantly different between the two groups after naloxone
      administration (p = 0.18, p = 0.17, p = 0.32). There was also no significant
      difference in the length of hospital stay between the two groups (p = 0.14).
      CONCLUSIONS: Intranasal naloxone is as effective as IV naloxone in reversing both
      respiratory depression and depressive effects on the central nervous system
      caused by opioid overdose.

PMID- 24904668
TI  - Prevalence of Demodex spp. in eyelash follicles in different populations.
AB  - INTRODUCTION: The pathologic relevance of Demodex infestation in blepharitis is
      still controversial. The aim of the study was to determine the prevalence of
      Demodex spp. in eyelash follicles and its relationship to eye symptoms. MATERIAL
      AND METHODS: A total of 290 individuals were studied for the presence of Demodex
      folliculorum and Demodex brevis within eyelash follicles. Participants belonged
      to one of four groups: inpatients, drug abusers, health professionals, and
      medical students. Ten eyelashes were epilated from each subject, placed on
      microscope slides and examined for parasites. The sample was defined as positive
      if at least one parasite or parasite's ova were present. The presence of
      parasites was analyzed according to age, gender, place of living, reported eye
      problems, and use of contact lenses or glasses. RESULTS: The prevalence of
      Demodex spp. infestation among all studied subjects was 41%, with the highest
      infestation rate among inpatients (p < 0.01) and elderly people (p < 0.001). No
      difference regarding the presence of Demodex was found between women and men (p =
      0.76). Demodex folliculorum was about 2.4 times more frequent than D. brevis. The
      prevalence of Demodex spp. in subjects with and without eye complaints suggesting
      blepharitis was similar (41.6% vs. 40.2%, respectively, p = 0.9). On the other
      hand, wearing glasses was linked to Demodex infestation (48.4% vs. 32.3%, p <
      0.01). CONCLUSIONS: Demodex is a common saprophyte found in human eyelash
      follicles. Its presence might be related to some ocular discomfort; however, in
      the vast majority of cases the infestation seems to be asymptomatic.

PMID- 24904669
TI  - HLA-DR expression, cytokines and bioactive lipids in sepsis.
AB  - Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both
      inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the
      early phase dominated by the hyperinflammatory response and the late phase by
      immunosuppression. This late immunosuppression phase leads to loss of the delayed
      type hypersensitivity response, failure to clear the primary infection and
      development of secondary infections. Based on the available data, I hypothesize
      that failure to produce adequate amounts of inflammation resolving lipid
      mediators may be at the centre of both the hyperinflammatory response and late
      immunosuppression seen in sepsis. These proresolving lipids - lipoxins, resolvins
      and protectins - suppress exacerbated activation of leukocytes and macrophages,
      inhibit excess production of pro-inflammatory cytokines, initiate resolution of
      inappropriate inflammation, augment clearance of bacteria and other pathogens,
      and restore homeostasis. If true, this implies that administration of naturally
      occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves
      or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)
      lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)
      methyl-LXA4 may form a new approach in the prevention (in the high-risk
      subjects), management of sepsis and in resolving the imbalanced inflammatory
      process such that sepsis is ameliorated early. In addition, recent studies have
      suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also
      have a role in the pathobiology of sepsis. It is suggested that both nociceptin
      and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins,
      and nitrolipids and thus play a role in sepsis and septic shock. 

PMID- 24904670
TI  - Dietary and nutraceutical approach to type 2 diabetes.
AB  - Nutritional medical treatment is the first step to achieve adequate glycemic
      control and prevent diabetic complications. Lifestyle changes include moderate
      weight loss (7%) and regular physical activity (150 min/week). The appropriate
      diet composition is < 30% total fat, < 10% saturated fats, > 15 g/1000 kcal
      fiber, half soluble, 45-60% of carbohydrates with amoderate intake of sugar (50
      g/day) and protein intake of 15-20% of the total calories a day. Patients need to
      limit the intake of saturated fats to < 7% of the daily calorie intake.
      Monounsaturated fatty acids such as olive oil and other vegetable oils are
      recommended. L-carnitine, alpha-lipoic acid, berberine and omega-3 fatty acids
      can be useful supplements. 

PMID- 24904672
TI  - General public awareness of heart failure: results of questionnaire survey during
      Heart Failure Awareness Day 2011.
AB  - INTRODUCTION: General public views about heart failure (HF) alone and in
      comparison with other chronic conditions are largely unknown; thus we conducted
      this survey to evaluate general public awareness about HF and HF disease burden
      relative to common chronic disease. MATERIAL AND METHODS: This was a cross
      sectional survey during European Heart Failure Awareness Day 2011. People
      visiting the stands and other activities in 12 Slovenian cities were invited to
      complete a 14-item questionnaire. RESULTS: The analysis included 850 subjects
      (age 56 +/-15 years, 44% men, 55% completed secondary education or higher).
      Overall, 83% reported to have heard about HF, 58% knew someone with HF, and 35%
      believed that HF is a normal consequence of ageing. When compared to other
      chronic diseases, HF was perceived as less important than cancer, myocardial
      infarction, stroke and diabetes with only 6%, 12%, 7%, and 5% of subjects ranking
      HF as number 1 in terms of prevalence, cost, quality of life, and survival. A
      typical patient with HF symptoms was recognized by 30%, which was comparable to
      the description of myocardial ischemia (33%) and stroke (39%). Primary care
      physicians (53%) or specialists (52%) would be primary sources of information
      about HF. If experiencing HF, 83% would prefer their care to be focused on
      quality of life rather than on survival (14%). CONCLUSIONS: Many participants
      reported to have heard about heart failure but the knowledge was poor and with
      several misbeliefs. Heart failure was perceived as less important than several
      other chronic diseases, where cancer appears as a main concern among the general
      public.

PMID- 24904671
TI  - Advances in the diagnosis and management of diabetic distal symmetric
      polyneuropathy.
AB  - Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of
      diabetes mellitus. The pathogenesis of DSPN is not fully elucidated, but it is
      certainly multifactorial in nature and attributable to metabolic and microvessel
      disorders related to chronic hyperglycemia, diabetes duration, and several
      cardiovascular risk factors. Early diagnosis and appropriate management are
      extremely important, since up to 50% of DSPN cases may be asymptomatic, and
      patients are unaware of foot injury leading to foot ulcers and amputation.
      Simple, validated tests such as the Neuropathy Disability Score and/or Vibration
      Perception Threshold may be used to diagnose DSPN. Similarly, neurological
      dysfunction screening questionnaires should be used to assess the quality and
      severity of DSPN symptoms. Using both methods enables prediction of the prognosis
      of diabetic patients with DSPN. No causative treatment of DSPN is known, but the
      results of clinical trials indicate that several treatment options are highly
      effective in symptomatic treatment of painful DSPN. The appropriate treatment of
      DSPN may improve the outcome, preventing or delaying the development of numerous
      diabetic complications. 

PMID- 24904673
TI  - Quality of pregnant women's diet in Poland - macro-elements.
AB  - INTRODUCTION: The objective was to assess the quality of pregnant women's diet in
      Poland concerning macro-elements and to analyze reasons for low or high quality
      diets. MATERIAL AND METHODS: Five hundred and twelve pregnant women in their
      20(th) to 30(th) week of pregnancy took part in the research conducted by means
      of a 7-day observation of diet. Consumed products were analyzed by means of
      DIETETYK software developed by the Polish National Food and Nutrition Institute.
      Obtained macro values were averaged. The results were compared with the
      recommendations from the World Health Organization, European Union and Polish
      National Food and Nutrition Institute and analyzed statistically (chi(2) test).
      RESULTS: The pregnant women consumed an average of 1898 +/-380 kcal daily.
      Average value of macro components supplied with the diet did not deviate from EU
      and NFNI nutrition recommendations: protein - 72.1 g/person daily, fats overall -
      72.8 g, polyunsaturated fatty acids - 10.93 g, cholesterol - 283 mg,
      carbohydrates - 257 g. The study proved a significant relation between a higher
      quality diet of pregnant women and tertiary or secondary education (p = 0.05) as
      well as urban residence (p = 0.01). CONCLUSIONS: Pregnant women's diet in Poland
      is not significantly different from diet quality of pregnant women from other
      countries. A lower quality diet was observed among women who smoked during
      pregnancy and lived in rural areas.

PMID- 24904674
TI  - A glimpse into the early origins of medieval anatomy through the oldest conserved
      human dissection (Western Europe, 13(th) c. A.D.).
AB  - INTRODUCTION: Medieval autopsy practice is very poorly known in Western Europe,
      due to a lack of both descriptive medico-surgical texts and conserved dissected
      human remains. This period is currently considered the dark ages according to a
      common belief of systematic opposition of Christian religious authorities to the
      opening of human cadavers. MATERIAL AND METHODS: The identification in a private
      collection of an autopsied human individual dated from the 13(th) century A.D. is
      an opportunity for better knowledge of such practice in this chrono-cultural
      context, i.e. the early origins of occidental dissections. A complete forensic
      anthropological procedure was carried out, completed by radiological and
      elemental analyses. RESULTS: The complete procedure of this body opening and
      internal organs exploration is explained, and compared with historical data about
      forensic and anatomical autopsies from this period. During the analysis, a red
      substance filling all arterial cavities, made of mercury sulfide (cinnabar) mixed
      with vegetal oil (oleic and palmitic acids) was identified; it was presumably
      used to highlight vascularization by coloring in red such vessels, and help in
      the preservation of the body. CONCLUSIONS: Of particular interest for the
      description of early medical and anatomical knowledge, this "human preparation"
      is the oldest known yet, and is particularly important for the fields of history
      of medicine, surgery and anatomical practice.

PMID- 24904675
TI  - Electrophysiological effect of rotigaptide in rabbits with heart failure.
AB  - INTRODUCTION: Rotigaptide is a new anti-arrhythmic peptide, which has recently
      been found to increase junctional conductance and prevent ischemia-induced
      ventricular tachycardia. In this study, we attempted to investigate the effects
      and mechanisms of rotigaptide on the vulnerability to ventricular arrhythmias in
      rabbits with heart failure (HF). MATERIAL AND METHODS: Chronic volume-pressure
      overload was used to induce HF. After rotigaptide infusion, an
      electrophysiological study was performed to record monophasic action potential
      (MAP), determine the effective refractory period (ERP) and ventricular
      fibrillation threshold (VFT), and assess the susceptibility to ventricular
      arrhythmia. Finally, real-time PCR was used to detect the changes of connexin 43
      (Cx43) mRNA expression. RESULTS: HF rabbits exhibited significant down-regulation
      of Cx43 mRNA, increase of effective refractory period (ERP) and decrease of VFT
      (p < 0.05, respectively). These changes resulted in an increase of vulnerability
      to ventricular tachyarrhythmias (VT/VF). Rotigaptide administration shortened ERP
      (113.3 +/-8.6 ms vs. 131.7 +/-12.5 ms, p < 0.05), restored VFT (15.0 +/-2.0 V vs.
      6.3 +/-1.4 V, p < 0.05), and decreased the vulnerability to VT/VF. However, short
      term rotigaptide treatment had no significant effect on MAP duration (MAP
      duration at 90% repolarization: 169.3 +/-6.0 ms vs. 172.7 +/-6.2 ms, p > 0.05) or
      connexin 43 mRNA expression (p > 0.05). CONCLUSIONS: Rotigaptide decreases the
      ERP, elevates VFT, and reduces the vulnerability to ventricular arrhythmias
      without changing Cx43 expression in rabbits with HF. It may be a promising
      antiarrhythmic drug for preventing ventricular arrhythmia in HF.

PMID- 24904676
TI  - Effect of glucocorticoids on indomethacin-induced gastric ulcer in the adult male
      albino rat - histological, morphometric and electron microscopy study.
AB  - INTRODUCTION: Indomethacin is a non steroidal anti-inflammatory drug (NSAID)
      which is capable of producing injury to gastric mucosa. To prevent of NSAID
      induced gastropathy, it is important to evaluate the risk factors. One of them is
      steroid. The aim is to study time dependent effects of glucocorticoids (GC) on
      indomethacin induced gastric ulcer. MATERIAL AND METHODS: Forty-nine albino rats
      were used. They were divided into control and experimental groups. The
      experimental group was subgroup I (rats were given indomethacin and were
      sacrificed 1 day after drug intake), subgroup II (rats were given indomethacin +
      dexamethasone and were sacrificed 1 day after drug intake), subgroup III (rats
      were given indomethacin + dexamethasone and were sacrificed 3 days after drug
      intake) and subgroup IV (rats were given indomethacin + dexamethasone and were
      sacrificed 7 days day after drug intake). Histological, scanning electron
      microscopy and morphometric studies were used. RESULTS: Indomethacin induced
      gastric ulceration with shredding of the superficial epithelial cells. The fundic
      glands were dilated in the subgroups II, III, IV. The surface epithelial cells
      were shredded and the ulcer sizes were big in subgroup IV. All subgroups
      exhibited abnormal surface epithelial cells within the gastric ulcer area.
      CONCLUSIONS: Indomethacin is capable of producing injury to gastrointestinal
      mucosa. With prolonged use of GC the surface epithelial cells became more
      affected and the ulcer sizes became bigger. Concomitant use of both medications
      will delay the healing of the indomethacin induced gastric ulcer and induce more
      gastric complication.

PMID- 24904677
TI  - Improved methodology to obtain large quantities of correctly folded recombinant N
      terminal extracellular domain of the human muscle acetylcholine receptor for
      inducing experimental autoimmune myasthenia gravis in rats.
AB  - INTRODUCTION: Human myasthenia gravis (MG) is an autoimmune disorder of the
      neuromuscular system. Experimental autoimmune myasthenia gravis (EAMG) is a well
      established animal model for MG that can be induced by active immunization with
      the Torpedo californica-derived acetylcholine receptor (AChR). Due to the
      expensive cost of purifying AChR from Torpedo californica, the development of an
      easier and more economical way of inducing EAMG remains critically needed.
      MATERIAL AND METHODS: Full-length cDNA of the human skeletal muscle AChR alpha1
      subunit was obtained from TE671 cells. The DNA fragment encoding the
      extracellular domain (ECD) was then amplified by polymerase chain reaction (PCR)
      and inserted into pET-16b. The reconstructed plasmid was transformed into the
      host strain BL21(DE3)pLysS, which was derived from Escherichia coli. Isopropyl
      beta-D-thiogalactopyranoside (IPTG) was used to induce the expression of the N
      terminal ECD. The produced protein was purified with immobilized Ni(2+) affinity
      chromatography and refolded by dialysis. RESULTS: The recombinant protein was
      efficiently refolded to soluble active protein, which was verified by ELISA.
      After immunization with the recombinant ECD, all rats acquired clinical signs of
      EAMG. The titer of AChR antibodies in the serum was significantly higher in the
      EAMG group than in the control group, indicating successful induction of EAMG.
      CONCLUSIONS: We describe an improved procedure for refolding recombinant ECD of
      human muscle AChR. This improvement allows for the generation of large quantities
      of correctly folded recombinant ECD of human muscle AChR, which provides for an
      easier and more economical way of inducing the animal model of MG.

PMID- 24904679
TI  - Diabetes insipidus as a main symptom of cancer.

PMID- 24904678
TI  - Effect of Hypericum perforatum on intraperitoneal adhesion formation in rats.
AB  - INTRODUCTION: The aim of this study was to evaluate the efficacy of Hypericum
      perforatum for prevention of adhesion formation in rats. MATERIAL AND METHODS:
      Twenty-four female wistar rats underwent left uterine horn adhesion model. Rats
      were randomised into 4 groups. Group 1 (Control): Closure of abdominal incision
      without any agent administration. Group 2: Closure of incision after
      administration of intraperitoneal (i.p.) Ringer's lactate solution. Group 3:
      Closure of incision after administration of i.p. olive oil (diluent of H.
      perforatum). Group 4: Hypericum perforatum extract (Ecodab((r))) was administered
      i.p. before the closure of incision. Fourteen days later, relaparatomy was
      performed and surgical adhesion scores, inflammation and fibrosis scores were
      noted. Groups were compared according to these scores. RESULTS: There was
      statistical significant difference between ringer's lactate group and olive oil
      group according to surgical adhesion score (p = 0.009). However, groups were not
      different according to inflammation and fibrosis scores (p > 0.05). CONCLUSIONS:
      Despite antiinflammatory, antioxidants and antimicrobial properties of H.
      perforatum, our results revealed no positive effect of H. perforatum on the
      prevention of intraperitoneal adhesion formation.

PMID- 24904680
TI  - Favorable outcome in non-Hodgkin lymphoma of the maxillary sinus treated with R
      CHOP.

PMID- 24904681
TI  - Computational modeling helps uncover mechanisms related to the progression of
      emphysema.
AB  - Emphysema is a progressive disease characterized by deterioration of alveolar
      structure and decline in lung function. While morphometric and molecular biology
      studies have not fully uncovered the underlying mechanisms, they have produced
      data to advance computational modeling. In this review, we discuss examples in
      which modeling has led to novel insight into mechanisms related to disease
      progression. Finally, we propose a general scheme of multiscale modeling approach
      that could help unravel the progressive nature of emphysema and provide patient
      specific mechanisms perhaps suitable for use in treatment therapies.

PMID- 24904682
TI  - A genotypic HIV-1 proviral DNA coreceptor tropism assay: characterization in
      viremic subjects.
AB  - BACKGROUND: HIV-1 coreceptor tropism testing is used to evaluate eligibility for
      CCR5 antagonist therapy. However, HIV-1 RNA-based tests are not suitable for
      virologically suppressed patients, therefore the use of proviral DNA tropism
      testing has been investigated. We describe a novel proviral DNA-based genotypic
      tropism assay and compare its performance to that of a sensitive HIV-1 RNA-based
      genotypic test. METHODS: Tropism was determined using HIV-1 plasma RNA and
      proviral DNA from 42 paired samples from patients with plasma viral loads >=1000
      HIV-1 RNA copies/mL. Proviral DNA sample types included whole blood, separated
      peripheral blood mononuclear cells resuspended in phosphate-buffered saline and
      peripheral blood mononuclear cells resuspended in spun plasma. The HIV-1 envelope
      V3 region was PCR-amplified, sequenced in triplicate, and analyzed for tropism
      with the geno2pheno algorithm using a 10% false-positive rate (FPR). RESULTS:
      Amplicons were obtained from proviral DNA and plasma RNA in 41/42 samples.
      Tropism predictions were highly concordant (93%-98%) between proviral DNA and
      plasma RNA, regardless of the proviral DNA isolation method. Non-R5 proviral DNA
      results were obtained for 100% of patients with detectable non-R5 plasma HIV-1
      RNA results. Geno2pheno FPRs for proviral DNA and plasma RNA were highly
      correlated (Spearman rho = 0.86). CONCLUSIONS: Our findings demonstrate that
      proviral DNA tropism determinations from whole blood or peripheral blood
      mononuclear cells were highly concordant with plasma HIV-1 RNA tropism
      determinations. This assay may be useful for screening virologically suppressed
      patients for CCR5-antagonist eligibility and for research purposes.

PMID- 24904683
TI  - Prevalence of exclusive breastfeeding and associated factors among mothers in
      rural Bangladesh: a cross-sectional study.
AB  - BACKGROUND: Exclusive breastfeeding (EBF) means that the infant receives only
      breast milk for the first six months of life after birth. In Bangladesh, the
      prevalence of EBF remained largely unchanged for nearly two decades and was 43%
      in 2007. However, in 2011, a prevalence of 64% was reported, an increase by 21
      percentage points. The reasons for this large change remain speculative at this
      point. Thus to investigate the issue further, this study was conducted. The
      objective was to assess the prevalence of EBF and associated factors among
      mothers having children aged 0-6 months in rural Bangladesh. METHODS: A cross
      sectional study was conducted in Mirzapur Upazilla (sub district) among 121
      mothers of infants aged 0-6 months. Eligible mothers were identified and randomly
      selected using the demographic surveillance system's computerized database that
      is updated weekly. A semi-structured questionnaire was used for interviews that
      inquired information on socio-demographic characteristics, obstetric, health
      service, breastfeeding related factors (initiation of breastfeeding, prelacteal
      feeding and colostrum feeding) and economic factors. EBF prevalence was
      calculated using 24 hour recall method. In multivariate analysis, a logistic
      regression model was developed using stepwise modeling to analyze the factors
      associated with EBF. RESULTS: The prevalence of EBF in the last 24 hours
      preceding the survey was 36%. Bivariate and multivariate analysis revealed no
      significant association between EBF and its possible predictors at 0.05 level of
      alpha. However, there was some evidence of an association between EBF and having
      a caesarean delivery (OR = 0.47, 95% CI: 0.21, 1.06). In multivariate analysis,
      type of delivery: caesarean (AOR = 0.45, 95% CI: 0.19, 1.03) and wealth quintile:
      richer (AOR = 2.40, 95% CI: 0.94, 6.16) also showed some evidence of an
      association with EBF. CONCLUSION: The prevalence of EBF in Mirzapur (36%) is
      lower than the national figure (64%). Prelacteal feeding was not uncommon. These
      findings suggest that there is a need for breastfeeding support provided by
      health services. Hence, promotion of EBF during the first six months of life
      needs to be addressed and future breastfeeding promotion programmes should give
      special attention to those women who are not practicing EBF.

PMID- 24904684
TI  - Genes and environment: effects on the development of second malignancies in
      retinoblastoma survivors.
AB  - Although it is a rare cancer, retinoblastoma has served as an important model in
      our understanding of genetic cancer syndromes. All patients with a germinal rb1
      mutation possess a risk of the development of second malignancies. Approximately
      40-50% of all retinoblastoma cases are considered germinal cases and recent work
      has indicated that nearly all retinoblastoma patients probably demonstrate a
      degree of mosaicism for the rb1 mutation, and thus are at risk of secondary
      malignancies. The risk of the development of these cancers continues throughout
      the patients' lives due to the loss of a functional RB1 protein and its critical
      tumor suppressive function in all cells. These cancers can develop in diverse
      anatomic locations, including the skull and long bones, soft tissues, nasal
      cavity, skin, orbit, brain, breast and lung. Treatments used for retinoblastoma
      such as external-beam radiation and chemotherapy can have a significant impact on
      the risk for and pattern of development of these secondary cancers. Second
      malignancies are the leading cause of death in germinal retinoblastoma survivors
      in the USA and thus continue to be an important subject of study in this patient
      population. Second malignancies following the germinal form of retinoblastoma are
      the subject of this review.

PMID- 24904686
TI  - Prognosis and delay of diagnosis among Kaposi's sarcoma patients in Uganda: a
      cross-sectional study.
AB  - BACKGROUND: In low- and middle-income countries, the association between delay to
      treatment and prognosis for Kaposi's sarcoma (KS) patients is yet to be studied.
      METHODS: This is a prospective study of HIV-infected adults with histologically
      confirmed KS treated at the Uganda Cancer Institute (UCI). Standardized
      interviews were conducted in English or Luganda. Medical records were abstracted
      for KS stage at admission to UCI. Multivariable logistic regression assessed
      relationships between diagnostic delay and stage at diagnosis. RESULTS: Of 161
      patients (90% response rate), 69% were men, and the mean age was 34.0 years (SD
      7.7). 26% had been seen in an HIV clinic within 3 months, 72% were on
      antiretroviral therapy, and 26% had visited a traditional healer prior to
      diagnosis. 45% delayed seeking care at UCI for >=3 months from symptom onset.
      Among those who delayed, 36% waited 6 months, and 25% waited 12 months. Common
      reasons for delay were lack of pain (48%), no money (32%), and distance to UCI
      (8%). In adjusted analysis patients who experienced diagnostic delay were more
      likely than those who did not delay to have poor-risk KS stage (OR 3.41, p =
      0.002, 95% CI: 1.46-7.45). In adjusted analyses visiting a traditional healer was
      the only variable associated with greater likelihood of delay (OR 2.69, p =
      0.020, 95% CI: 1.17-6.17). CONCLUSIONS: Diagnostic delay was associated with poor
      risk stage at diagnosis, and visiting a traditional healer was associated with
      higher odds of delay. The relationship between traditional and Western medicine
      presents a critical intervention point to improve KS-related outcomes in Uganda.

PMID- 24904685
TI  - Lemierre's disease: a case with bilateral iliopsoas abscesses and a literature
      review.
AB  - Lemierre's disease is characterized by sepsis, often with an oropharyngeal
      source, secondary septic emboli and internal jugular vein thrombosis (Lancet
      1:701-3, 1936. Clin Microbiol Rev 20(4):622-59, 2007). Septic emboli affecting
      many bodily sites have been reported, including the lungs, joints, bones, and
      brain. The case report describes an unusual case of Lemierre's disease in a 64
      year old gentleman causing profound sepsis, acute kidney injury, bilateral
      iliopsoas abscesses and a right hand abscess. To our knowledge, this is the first
      reported case of Lemierre's disease in the context of bilateral psoas abscesses,
      and highlights the ambiguity surrounding the definition of Lemierre's disease.
      The clinical literature review highlights the difficulty in definitively
      diagnosing the condition and offers some suggestions for recognising and refining
      the diagnostic criterion of Lemierre's. 

PMID- 24904687
TI  - Modeling students' instrumental (mis-) use of substances to enhance cognitive
      performance: Neuroenhancement in the light of job demands-resources theory.
AB  - BACKGROUND: Healthy university students have been shown to use psychoactive
      substances, expecting them to be functional means for enhancing their cognitive
      capacity, sometimes over and above an essentially proficient level. This behavior
      called Neuroenhancement (NE) has not yet been integrated into a behavioral theory
      that is able to predict performance. Job Demands Resources (JD-R) Theory for
      example assumes that strain (e.g. burnout) will occur and influence performance
      when job demands are high and job resources are limited at the same time. The aim
      of this study is to investigate whether or not university students' self-reported
      NE can be integrated into JD-R Theory's comprehensive approach to psychological
      health and performance. METHODS: 1,007 students (23.56 +/- 3.83 years old, 637
      female) participated in an online survey. Lifestyle drug, prescription drug, and
      illicit substance NE together with the complete set of JD-R variables (demands,
      burnout, resources, motivation, and performance) were measured. Path models were
      used in order to test our data's fit to hypothesized main effects and
      interactions. RESULTS: JD-R Theory could successfully be applied to describe the
      situation of university students. NE was mainly associated with the JD-R Theory's
      health impairment process: Lifestyle drug NE (p < .05) as well as prescription
      drug NE (p < .001) is associated with higher burnout scores, and lifestyle drug
      NE aggravates the study demands-burnout interaction. In addition, prescription
      drug NE mitigates the protective influence of resources on burnout and on
      motivation. CONCLUSION: According to our results, the uninformed trying of NE
      (i.e., without medical supervision) might result in strain. Increased strain is
      related to decreased performance. From a public health perspective, intervention
      strategies should address these costs of non-supervised NE. With regard to future
      research we propose to model NE as a means to reach an end (i.e. performance
      enhancement) rather than a target behavior itself. This is necessary to provide a
      deeper understanding of the behavioral roots and consequences of the phenomenon.

PMID- 24904688
TI  - Genome-wide RNAi screen reveals the E3 SUMO-protein ligase gene SIZ1 as a novel
      determinant of furfural tolerance in Saccharomyces cerevisiae.
AB  - BACKGROUND: Furfural is a major growth inhibitor in lignocellulosic hydrolysates
      and improving furfural tolerance of microorganisms is critical for rapid and
      efficient fermentation of lignocellulosic biomass. In this study, we used the
      RNAi-Assisted Genome Evolution (RAGE) method to select for furfural resistant
      mutants of Saccharomyces cerevisiae, and identified a new determinant of furfural
      tolerance. RESULTS: By using a genome-wide RNAi (RNA-interference) screen in S.
      cerevisiae for genes involved in furfural tolerance, we identified SIZ1, a gene
      encoding an E3 SUMO-protein ligase. Disruption of SIZ1 gene function by knockdown
      or deletion conferred significantly higher furfural tolerance compared to other
      previously reported metabolic engineering strategies in S. cerevisiae. This
      improved furfural tolerance of siz1Delta cells is accompanied by rapid furfural
      reduction to furfuryl alcohol and leads to higher ethanol productivity in the
      presence of furfural. In addition, the siz1Delta mutant also exhibited tolerance
      towards oxidative stress, suggesting that oxidative stress tolerance related
      proteins may be under the SUMO regulation of SIZ1p and responsible for furfural
      tolerance. CONCLUSIONS: Using a genome-wide approach, we identified a novel
      determinant for furfural tolerance, providing valuable insights into the design
      of recombinant microbes for efficient lignocellulose fermentation.

PMID- 24904689
TI  - Ventricular trigeminy in a patient with serologically confirmed dengue
      haemorrhagic fever.
AB  - BACKGROUND: Cardiac arrhythmias occur during the acute stage of Dengue
      Haemorrhagic Fever. Dengue myocarditis is the most likely cause of the
      arrhythmias. CASE PRESENTATION: We report a 55-year-old patient with Dengue
      Haemorrhagic Fever presenting with transient ventricular trigeminy which has not
      been reported before. CONCLUSION: Among many other known cardiac arrhythmia seen
      in DHF, ventricular trigeminy is also a possibility. Clinicians should be aware
      of this cardiac rhythm abnormality that can occur in dengue patients.

PMID- 24904690
TI  - Analysis of DNA methylation acquisition at the imprinted Dlk1 locus reveals
      asymmetry at CpG dyads.
AB  - BACKGROUND: Differential distribution of DNA methylation on the parental alleles
      of imprinted genes distinguishes the alleles from each other and dictates their
      parent of origin-specific expression patterns. While differential DNA methylation
      at primary imprinting control regions is inherited via the gametes, additional
      allele-specific DNA methylation is acquired at secondary sites during embryonic
      development and plays a role in the maintenance of genomic imprinting. The
      precise mechanisms by which this somatic DNA methylation is established at
      secondary sites are not well defined and may vary as methylation acquisition at
      these sites occurs at different times for genes in different imprinting clusters.
      RESULTS: In this study, we show that there is also variability in the timing of
      somatic DNA methylation acquisition at multiple sites within a single imprinting
      cluster. Paternal allele-specific DNA methylation is initially acquired at
      similar stages of post-implantation development at the linked Dlk1 and Gtl2
      differentially methylated regions (DMRs). In contrast, unlike the Gtl2-DMR, the
      maternal Dlk1-DMR acquires DNA methylation in adult tissues. CONCLUSIONS: These
      data suggest that the acquisition of DNA methylation across the Dlk1/Gtl2
      imprinting cluster is variable. We further found that the Dlk1 differentially
      methylated region displays low DNA methylation fidelity, as evidenced by the
      presence of hemimethylation at approximately one-third of the methylated CpG
      dyads. We hypothesize that the maintenance of DNA methylation may be less
      efficient at secondary differentially methylated sites than at primary imprinting
      control regions.

PMID- 24904692
TI  - Mobile DNA: an evolving field.
AB  - During the Mobile Genetic Elements and Genome Evolution Keystone Symposium in
      March 2014, the Editors of Mobile DNA caught up with a panel of conference
      speakers to select key advances in the field, and hear their thoughts on where
      mobile DNA research is going. 

PMID- 24904693
TI  - Epigenetic analyses of the insulin-like growth factor binding protein 1 gene in
      type 1 diabetes and diabetic nephropathy.
AB  - BACKGROUND: Clinical observations have demonstrated that high levels of
      circulating insulin-like growth factor binding protein-1 (IGFBP-1) are associated
      with type 1 diabetes (T1D), whereas low serum IGFBP-1 levels are associated with
      the risk of type 2 diabetes (T2D). Recently, we reported that increased DNA
      methylation levels in the IGFBP1 gene were associated with T2D. In the present
      study, we evaluated the epigenetic changes of IGFBP1 in T1D and diabetic
      nephropathy (DN). RESULTS: In total, 778 Swedish individuals, including T1D
      patients with or without DN and subjects with the normal glucose tolerance (NGT),
      were involved in the study. IGFBP1 methylation levels in genomic DNA extracted
      from peripheral blood were analyzed with bisulfite pyrosequencing. Serum IGFBP-1
      levels were measured with radioimmunoassay. We found that DNA methylation levels
      in the IGFBP1 gene were decreased (15.6% versus 16.9%; P < 0.001), whereas serum
      IGFBP-1 levels were increased (31 versus 24 MUg/L, P = 0.003) in T1D patients
      compared with NGT subjects. Furthermore, T1D patients with DN had increased
      circulating IGFBP-1 concentration compared with the patients without DN (52
      versus 28 MUg/L; P = 0.006). However, no difference of the IGFBP1 DNA methylation
      levels between T1D patients with and without DN was observed. CONCLUSIONS: This
      study shows for the first time that T1D patients had decreased DNA methylation
      levels in the IGFBP1 gene and further implies that increased circulating IGFBP-1
      levels are associated with T1D and DN.

PMID- 24904694
TI  - News from the NIH: research to evaluate "natural experiments" related to obesity
      and diabetes.

PMID- 24904695
TI  - What influences park use and physical activity?

PMID- 24904696
TI  - School factors as barriers to and facilitators of a preventive intervention for
      pediatric type 2 diabetes.
AB  - School-based interventions are essential to prevent pediatric obesity and type 2
      diabetes. School environmental factors influence implementation of these
      interventions. This article examines how school factors acted as barriers to and
      facilitators of the HEALTHY intervention. The HEALTHY study was a cluster
      randomized trial of a multicomponent intervention implemented in 21 schools.
      Interview data were analyzed to identify barriers and facilitators. Barriers
      included teacher frustration that intervention activities detracted from tested
      subjects, student resistance and misbehavior, classroom management problems,
      communication equipment problems, lack of teacher/staff engagement, high cost and
      limited availability of nutritious products, inadequate facility space, and large
      class sizes. Facilitators included teacher/staff engagement, effective classroom
      management, student engagement, schools with direct control over food service,
      support from school leaders, and adequate facilities and equipment. Contextual
      barriers and facilitators must be taken into account in the design and
      implementation of school-based health interventions. 

PMID- 24904697
TI  - Translation and sustainability of an HIV prevention intervention in Lusaka,
      Zambia.
AB  - The scale-up of HIV treatment programs in sub-Saharan Africa necessitates
      creative solutions that do not further burden the health system to meet global
      initiatives in prevention and care. This study assessed the work environment and
      impact of providing a behavioral risk reduction intervention in six community
      health centers (CHCs) in Lusaka, Zambia; opportunities and challenges to long
      term program sustainability were identified. CHC staff participants (n = 82) were
      assessed on perceived clinic burden, job satisfaction, and burnout before and
      after implementation of the intervention. High levels of clinic burden were
      identified; however, no increase in perceived clinic burden or staff burnout was
      associated with providing the intervention. The intervention was sustained at the
      majority of CHCs and also adopted at additional clinics. Behavioral interventions
      can be successfully implemented and maintained in resource-poor settings.
      Creative strategies to overcome structural and economic challenges should be
      applied to enhance translation research. 

PMID- 24904698
TI  - Translating the Diabetes Prevention Program in Native Hawaiian and Pacific
      Islander communities: the PILI 'Ohana Project.
AB  - Native Hawaiians/Pacific Islanders experience a high prevalence of
      overweight/obesity. The Diabetes Prevention Program Lifestyle Intervention (DPP
      LI) was translated into a 3-month community-based intervention to benefit these
      populations. The weight loss and other clinical and behavioral outcomes of the
      translated DPP-LI and the socio-demographic, behavioral, and biological factors
      associated with the weight loss were examined. A total of 239 Native
      Hawaiian/Pacific Islander adults completed the translated DPP-LI through four
      community-based organizations (CBOs). Changes from pre- to post-intervention
      assessments in weight, blood pressure, physical functioning, exercise frequency,
      and fat in diet were measured. Significant improvements on all variables were
      found, with differences observed across the four CBOs. CBOs with predominately
      Native Hawaiian and ethnically homogenous intervention groups had greater weight
      loss. General linear modeling indicated that larger baseline weight and CBO
      predicted weight loss. The translated DPP-LI can be effective for Native
      Hawaiians/Pacific Islanders, especially when socio-cultural, socio-economic, and
      CBO-related contextual factors are taken into account. 

PMID- 24904699
TI  - Translating a health behavior change intervention for delivery to 2-year college
      students: the importance of formative research.
AB  - Young adults are at risk for weight gain in the transition to independent
      adulthood; 2-year college students are at greater risk and understudied relative
      to 4-year students. This project conducted formative research for a randomized
      controlled weight gain prevention trial among 2-year college students, to ensure
      appropriateness of content and delivery of a curriculum originally developed for
      4-year college students. Data were collected from community college students,
      faculty, and staff from October 2009 to August 2011. Work included focus groups
      and key informant interviews, curriculum pilot testing, and social network and
      support website beta testing. Based on focus groups and interviews, program
      content, course delivery modes, and communication channels were adjusted to meet
      population interests and preferences. The course was delivered successfully in
      pilot testing, and the website was received well by beta testers. Formative work
      successfully guided program adaptations to address population needs. 

PMID- 24904700
TI  - The Affordable Care Act and implications for young adult health.
AB  - In the USA, young adults are most likely to be uninsured and least likely to
      report a usual source of medical care than any age group. The Patient Protection
      and Affordable Care Act (ACA) recognizes the critical need for expanded insurance
      coverage for this age group, and multiple provisions of the ACA address insurance
      coverage and health care utilization in young adults. This paper presents a brief
      overview of the challenges of maintaining health insurance coverage and accessing
      health care in young adults, provisions of the ACA relevant to young adults, and
      early impact of the ACA on young adult health insurance status and health care
      access and utilization. We offer policy suggestions for behavioral health
      providers to address continued challenges related to health care for young
      adults. 

PMID- 24904701
TI  - Implementing brief cognitive behavioral therapy in primary care: A pilot study.
AB  - Effective implementation strategies are needed to improve the adoption of
      evidence-based psychotherapy in primary care settings. This study provides pilot
      data on the test of an implementation strategy conducted as part of a multisite
      randomized controlled trial examining a brief cognitive-behavioral therapy versus
      usual care for medically ill patients in primary care, using a hybrid (type II)
      effectiveness/implementation design. The implementation strategy was multifaceted
      and included (1) modular-based online clinician training, (2) treatment fidelity
      auditing with expert feedback, and (3) internal and external facilitation to
      provide ongoing consultation and support of practice. Outcomes included
      descriptive and qualitative data on the feasibility and acceptability of the
      implementation strategy, as well as initial indicators of clinician adoption and
      treatment fidelity. Results suggest that a comprehensive implementation strategy
      to improve clinician adoption of a brief cognitive-behavioral therapy in primary
      care is feasible and effective for reaching high levels of adoption and fidelity.

PMID- 24904702
TI  - Development and application of an electronic health record information extraction
      tool to assess quality of pain management in primary care.
AB  - Chronic pain is one of the most common presenting problems in primary care.
      Standards and guidelines have been developed for managing chronic pain, but it is
      unclear whether primary care providers routinely engage in guideline-concordant
      care. The purpose of this study is to develop a tool for extracting information
      about the quality of pain care in the primary care setting. Quality indicators
      were developed through review of the literature, input from an interdisciplinary
      panel of pain experts, and pilot testing. A comprehensive coding manual was
      developed, and inter-rater reliability was established. The final tool consists
      of 12 dichotomously scored indicators assessing quality and documentation of pain
      care in three domains: assessment, treatment, and reassessment. Presence of
      indicators varied widely. The tool is reliable and can be utilized to gather
      valuable information about pain management in the primary care setting. 

PMID- 24904703
TI  - Process evaluation and proximal impact of an affect-based exercise intervention
      among adolescents.
AB  - The objective of this study was to evaluate the implementation and proximal
      impact of an intervention designed to enhance adolescents' affective experience
      during Physical Education (PE). Healthy adolescents (N = 74) were randomly
      assigned to an affect-based or a traditional exercise prescription. Intervention
      logs, observations and interviews documented the implementation of the
      intervention. Participants completed a 30-min exercise task at an intensity that
      felt "good" to them before and after the intervention. Study procedures were
      implemented successfully and students enjoyed study participation. The
      intervention had no impact on exercise intensity during PE or during the "feels
      good" exercise task. Among adolescents who manifested a negative affective
      response to moderate-intensity exercise at baseline, the selected intensity
      during the "feels-good" task increased over time. The intervention may have been
      too weak to impact behavior over and above a high-quality PE program. The results
      do suggest, however, that reluctant exercisers may choose to exercise at a higher
      intensity after experiencing a high-quality PE program in combination with heart
      rate monitoring. 

PMID- 24904704
TI  - Using qualitative comparative analysis to understand and quantify translation and
      implementation.
AB  - Understanding the factors that facilitate implementation of behavioral medicine
      programs into practice can advance translational science. Often, translation or
      implementation studies use case study methods with small sample sizes.
      Methodological approaches that systematize findings from these types of studies
      are needed to improve rigor and advance the field. Qualitative comparative
      analysis (QCA) is a method and analytical approach that can advance
      implementation science. QCA offers an approach for rigorously conducting
      translational and implementation research limited by a small number of cases. We
      describe the methodological and analytic approach for using QCA and provide
      examples of its use in the health and health services literature. QCA brings
      together qualitative or quantitative data derived from cases to identify
      necessary and sufficient conditions for an outcome. QCA offers advantages for
      researchers interested in analyzing complex programs and for practitioners
      interested in developing programs that achieve successful health outcomes. 

PMID- 24904705
TI  - Quitting the "Cancer Tube": a qualitative examination of the process of indoor
      tanning cessation.
AB  - This study examined health belief model (HBM) relevant constructs in the context
      of indoor tanning cessation. Telephone interviews were conducted between December
      2011 and April 2012 with participants drawn from the Growing Up Today Study
      (GUTS) population, specifically, former tanning bed users (N = 14, all females;
      mean age, 25.65 years) who reported frequent use in 2007, but had quit by 2010.
      Participants identified important motivations for quitting including health and
      financial reasons and the central role of family and friends in providing
      encouragement for indoor tanning cessation. However, participants also noted
      substantial barriers to maintaining indoor tanning quitting (e.g., social
      pressures to look good, tanning salon incentives). Participants' experience of
      withdrawal highlighted psychological factors more often than physical factors;
      some were open to resuming use in the future. The findings will be useful in
      intervention development to encourage cessation, the strengthening of policies to
      regulate the indoor tanning industry, as well as public health messaging to raise
      awareness of this prevalent, easily accessible cancer risk behavior. 

PMID- 24904706
TI  - How stable are stop smoking practitioner success rates over time?
AB  - Stop smoking practitioners appear to differ in effectiveness, but the stability
      of their success rates over time is unknown. The purpose of this study was to
      assess the degree of stability of success rates of stop smoking practitioners
      over several years of practice. Using routinely collected practice data, the
      success rates of 197 practitioners active between April 2009 and April 2012 in
      the English stop smoking services were correlated across years before and after
      adjusting for client and intervention characteristics. Changes in client and
      intervention characteristics were assessed. Success rates for individual
      practitioners correlated highly in successive years (r = 0.64 to 0.68, p < 0.001,
      ICC = 0.56) and moderately over non-successive years (r = 0.39 to 0.51, p <
      0.001). There was no evidence for increasing effectiveness over time.
      Practitioners' effectiveness is moderately stable over time. Research is needed
      to establish what characterises the practice of the more successful
      practitioners. 

PMID- 24904707
TI  - Harnessing the potential of older adults to measure and modify their
      environments: long-term successes of the Neighborhood Eating and Activity
      Advocacy Team (NEAAT) Study.

PMID- 24904709
TI  - The relationship between use of sexually explicit media and sexual risk behavior
      in men who have sex with men: exploring the mediating effects of sexual self
      esteem and condom use self-efficacy.
AB  - This study tests the following three hypotheses: 1) there is a direct association
      between consumption of sexually explicit media (SEM) depicting non-condom use and
      STI-related sexual risk behavior among men who have sex with men (MSM), 2) The
      association between SEM consumption and STI-related sexual risk behavior is
      mediated by men's sexual self-esteem, and 3) the relationship between SEM
      consumption and sexual risk behavior is mediated by condom use self-efficacy. A
      cross-sectional, Internet-based survey on exposure to SEM and sexual behavior of
      1,391 MSM in the USA was conducted in 2011. The results confirmed hypothesis 1
      and 3 while hypothesis 2 was rejected. Accordingly, a significant association
      between the use of SEM picturing condom use and STI related sexual risk behavior
      among MSM was found. Likewise, we found that the association between the use of
      SEM and sexual risk behavior was mediated by condom use self-efficacy in an
      indirect path. However, SEM did not influence sexual risk behavior via sexual
      self-esteem. To promote STI prevention, the actors in SEM may be used as role
      models in managing condom use in sexual contexts.

PMID- 24904710
TI  - Health, Education, and the Post-Retirement Evolution of Household Assets.
AB  - We explore the relationship between education and the evolution of wealth after
      retirement. Asset growth following retirement depends in part on health capital
      and financial capital accumulated prior to retirement, which in turn are strongly
      related to educational attainment. These "initial conditions" at retirement can
      have a lingering effect on subsequent asset evolution. We aim to disentangle the
      effects of education that operate through health and financial pathways (such as
      Social Security benefits and the general level of health) prior to retirement
      from the effects of education that impinge directly on asset evolution after
      retirement. We also consider the additional effects of education that are not
      captured through these pathways. We find a substantial effect of education on
      asset growth through each of the pathways as well as a substantial additional
      effect not captured by the identified pathways.

PMID- 24904711
TI  - Correlation analysis of histomorphometry and motor neurography in the median
      nerve rat model.
AB  - OBJECTIVE: Standard methods to evaluate the functional regeneration after injury
      of the rat median nerve are insufficient to identify any further differences of
      axonal nerve regeneration after restitution of motor recovery is completed. An
      important complementary method for assessing such differences is a
      histomorphometric analysis of the distal to lesion nerve fibers. Recently, an
      electrophysiological method has been proposed as a sensitive method to examine
      the quality of axonal nerve regeneration. METHODS: A linear regression analysis
      has been performed to correlate histomorphometric and neurographic data
      originating from 31 rats subjected to neurotmesis and immediate reconstruction of
      their right median nerve. RESULTS: A significant linear correlation between the
      velocity of neuromuscular conduction and the total number of nerve fibers (P =
      .037) as well as between the amplitude of compound muscle action potential and
      the total number of nerve fibers (P = .026) has been identified. Interestingly, a
      significant correlation between the velocity of neuromuscular conduction and the
      square root of the cross-sectional area of the nerve could be found (P = .008).
      This corresponds to a linear correlation between the velocity of neuromuscular
      conduction and the radius of the nerve. CONCLUSION: These results contribute in a
      better interpretation of morphological predictors of nerve regeneration and
      verify the previously described electrophysiological assessment in the median
      nerve rat model as a valid method.

PMID- 24904708
TI  - Early exposure to nicotine during critical periods of brain development:
      Mechanisms and consequences.
AB  - Tobacco use during pregnancy continues to be a major problem with more than 16%
      of pregnant women in the United States continuing to smoke during pregnancy.
      Tobacco smoke is known to contain more than 4,000 different chemicals, and while
      many of these compounds have the potential to interfere with proper
      neurodevelopment, there is direct evidence that nicotine, the major psychoactive
      substance present in tobacco, acts as a neuroteratogen. Nicotine activates, and
      subsequently desensitizes, neuronal nicotinic acetylcholine receptor subtypes
      (AChRs), which are expressed in the developing central nervous system (CNS) prior
      to the in-growth of cholinergic neurons. Nicotinic AChRs are present by the first
      trimester of development in both humans and rodents, and activation of these
      receptors by acetylcholine is thought to play a critical role in CNS development.
      The purpose of the current review is to provide an overview of the role that
      nicotinic AChRs play in the developing CNS and to describe the effects of
      nicotine exposure during early development on neuronal cell biology, nicotinic
      AChR expression and neurotransmitter system (e.g., dopamine, norepinephrine,
      serotonin) function. In particular, differences that occur as a result of the
      timing and duration of nicotine exposure will be discussed. Emphasis will be
      placed on preclinical studies examining particular periods of time which
      correspond to periods of prenatal development in humans (i.e., first, second and
      third trimesters). Finally, the effects of early nicotine exposure on
      neurobehavioral development as it pertains to specific disorders, i.e., attention
      deficit hyperactivity disorder (ADHD), depression and addiction, will be
      discussed.

PMID- 24904712
TI  - Exposure of a microvascular anastomotic coupler in head and neck reconstruction:
      a case report.
AB  - OBJECTIVE: We present a case of exposure of a microvascular anastomotic coupler.
      METHODS: We performed venous anastomoses using microvascular anastomotic couplers
      in head and neck reconstruction. RESULTS: A microvascular anastomotic coupler was
      exposed in the seventh month postoperation, and an anastomosed vein was
      disrupted. CONCLUSIONS: Although the usefulness of the microvascular anastomotic
      coupler in microsurgical flap reconstruction is not in doubt, as described
      previously, we believe that it is necessary to remember that use of a
      microvascular anastomotic coupler involves potential risks of exposure and
      anastomosed vessel disruption.

PMID- 24904713
TI  - Uncovering patterns of technology use in consumer health informatics.
AB  - Internet usage and accessibility has grown at a staggering rate, influencing
      technology use for healthcare purposes. The amount of health information
      technology (Health IT) available through the Internet is immeasurable and growing
      daily. Health IT is now seen as a fundamental aspect of patient care as it
      stimulates patient engagement and encourages personal health management. It is
      increasingly important to understand consumer health IT patterns including who is
      using specific technologies, how technologies are accessed, factors associated
      with use, and perceived benefits. To fully uncover consumer patterns it is
      imperative to recognize common barriers and which groups they disproportionately
      affect. Finally, exploring future demand and predictions will expose significant
      opportunities for health IT. The most frequently used health information
      technologies by consumers are gathering information online, mobile health
      (mHealth) technologies, and personal health records (PHRs). Gathering health
      information online is the favored pathway for healthcare consumers as it is used
      by more consumers and more frequently than any other technology. In regard to
      mHealth technologies, minority Americans, compared with White Americans utilize
      social media, mobile Internet, and mobile applications more frequently. Consumers
      believe PHRs are the most beneficial health IT. PHR usage is increasing rapidly
      due to PHR integration with provider health systems and health insurance plans.
      Key issues that have to be explicitly addressed in health IT are privacy and
      security concerns, health literacy, unawareness, and usability. Privacy and
      security concerns are rated the number one reason for the slow rate of health IT
      adoption.

PMID- 24904714
TI  - The effect of exercise training on the level of tissue IL-6 and vascular
      endothelial growth factor in breast cancer bearing mice.
AB  - OBJECTIVES: The goal of this study was assessing the prophylactic effect of
      exercise and its role as an adjuvant therapy on level of cytokines involved in
      angiogenesis in estrogen-dependent breast cancer. MATERIALS AND METHODS: Forty
      female BALB/c mice were randomly assigned to exercise-tumor-exercise (ETE),
      exercise-tumor-rest (ETR), rest-tumor-exercise (RTE) and rest-tumor-rest (RTR)
      groups. After orientation in the environment, two groups of mice performed
      continuous endurance exercise for 8 weeks, and thereafter estrogen-dependent
      MC4L2 cancer cells were injected to them. Then, one group of each of trained and
      non-trained mice performed endurance exercise 5 days per week for 6 weeks. Tumor
      volume was measured by a digital caliper weekly. Finally, the mice were
      sacrificed; tumor tissue was removed, immediately frozen and kept in -70 degrees
      C. Tumor sample was homogenized; levels of cytokines were measured and quantified
      using ELISA. RESULTS: There was significant reduction in the level of interlukin
      6 (IL-6) (P=0.001), Vascular endothelial growth factor (VEGF) (P=0.0001) and
      tumor volume (P=0.0001) among the groups performing endurance exercise after
      malignancy (RTE and ETE) in comparison with groups not performing endurance
      exercise (ETR and RTR), and these results were in agreement with tumor growth
      rate. CONCLUSION: Exercise can cause reduction in levels of pro-inflammatory
      cytokines in tumor tissue. Decreased IL-6 production could reduce the generation
      of VEGF, resulting in reduced intra-tumor angiogenesis. Due to reduction of the
      level of these cytokines in groups doing exercise before and after malignancy,
      exercise is presumed to be an adjuvant therapy in estrogen-receptor dependent
      tumors in addition to its effective prophylactic role.

PMID- 24904715
TI  - The effect of eight weeks endurance training and high-fat diet on appetite
      regulating hormones in rat plasma.
AB  - OBJECTIVES: Consumption of high-fat foods is one of the major causes of obesity.
      Physical exercise is a strategy used to counteract obesity. The aim of this study
      was to investigate the effect of eight weeks endurance training and high-fat diet
      (HFD) on appetite-regulating hormones in rat plasma. MATERIALS AND METHODS:
      TWENTY EIGHT MALE WISTAR RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS: Control
      group with standard diet (CSD), endurance training with a standard diet (ESD),
      control group with high-fat diet (CHFD) and endurance training with high-fat diet
      (EHFD). Twenty-four hr after the last training session, the blood samples were
      obtained and analyzed for hormones levels. RESULTS: The significant increased
      weight gain and food intake and decreased plasma nesfatin-1 and PYY3-36 levels
      were observed in CHFD group, while exercise under the HFD antagonized these
      effects. There were no significant changes in ghrelin, insulin and leptin levels
      in different groups. CONCLUSION: These results suggest that exercise can prevent
      fattening effect of HFD. Probably, performing exercise makes a reduction of food
      intake and weight gain in rat via the increase in nesfatin-1 and PYY levels.
      However, further studies are necessary to understand the exact mechanisms
      involved in this field.

PMID- 24904716
TI  - The protective activity of noscapine on renal ischemia-reperfusion injury in male
      Wistar rat.
AB  - OBJECTIVES: Bradykinin is a part of the kinin-kallikrein system which is involved
      in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non
      competitive antagonist of bradykinin receptors. Noscapine has been reported to to
      be able to protect some organs against ischemia-reperfusion injury but its effect
      on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the
      present study was designed to evaluate the effect of noscapine on renal ischemia
      reperfusion injury in rats. MATERIALS AND METHODS: Twenty four rats were randomly
      assigned to four groups; sham, RIR control, pre-and post-treatment with
      noscapine. To induce RIR injury, 20 days after right nephrectomy, animals
      underwent a midline laparotomy and the renal artery was clamped for 40 min to
      induce ischemia, and the clamp was then removed to allow reperfusion for 48 hr.
      Animals received noscapine or vehicle 1 hr before RIR or just prior to
      reperfusion. At the end of the experiment, animals were killed by cardiac
      exsanguination. Blood samples were collected to assess blood urea nitrogen (BUN)
      and creatinine. The kidneys were also removed for histopathlogical and western
      blot analysis. RESULTS: Noscapine treatment 1 hr before RIR or just prior to
      reperfusion protects the renal tissue structure as compared with the control. The
      expression levels of the studied inflammatory mediators, TNF-alpha and MCP-1in
      pretreated-, and treated-noscapine groups decreased as compared with the control
      group. The levels of BUN and creatinine in pre-, and post-treated noscapine
      groups were significantly lower than in control animals. CONCLUSION: Noscapine
      protects renal tissue structure and function against RIR through down-regulation
      of the inflammatory mediators.

PMID- 24904717
TI  - Numerical status of CD4(+)CD25(+)FoxP3(+) and CD8(+)CD28(-) regulatory T cells in
      multiple sclerosis.
AB  - OBJECTIVES: Regulatory T cells, including CD4+CD25+Fox3+ and CD8+CD28- cells play
      an important role in regulating the balance between immunity and tolerance. Since
      multiple sclerosis is an inflammatory autoimmune disease, regulatory T cells are
      considered to be involved in its pathogenesis. In this study, we investigated the
      circulatory numbers of the two mentioned types of regulatory T cells and also
      their association with different clinical characteristics in 84 multiple
      sclerosis patients. MATERIALS AND METHODS: 84 patients with multiple sclerosis
      and 75 normal individuals were studied. Demographic and clinical information of
      all participants were collected via questionnaire and clinical examination as
      well as MRI. The peripheral blood frequency of two different subgroups of
      regulatory T cells (CD4+ CD25+Foxp3+ and CD8+CD28- cells) were analyzed by flow
      cytometry using anti-human antibodies conjugated with CD4-FITC / CD25-PE/Foxp3-PE
      Cy5, CD3-PE/CD8a-PE-Cy5/CD28-FITC. RESULTS: The frequency of CD4+CD25+Foxp3+
      cells in multiple sclerosis patients was significantly less than that in healthy
      controls (P=0.006) and in mild forms less than that in sever forms (P=0.003).
      There was not any correlation between the frequency of regulatory T cells and
      different clinical variables. CONCLUSION: Our results showed that the number of
      CD4+CD25+Foxp3+ cells decreases significantly in multiple sclerosis patients,
      which probably shows the regulatory role of these cells in multiple sclerosis.

PMID- 24904718
TI  - Spectrofluorimetric determination of cefixime using terbium-danofloxacin probe.
AB  - OBJECTIVES: Cefixime (Cfx), is a semi-synthetic third-generation oral
      cephalosporin antibiotic that is prescribed for the treatment of susceptible
      infections. There are some procedures for the determination of Cfx in
      pharmaceutical formulations and biological samples. Herein a spectrofluorimetric
      method was proposed for Cfx determination based on the fluorescence quenching of
      terbium-danofloxacin (Tb(3+)-Dano) in the presence of Cfx. MATERIALS AND METHODS:
      Cfx was detected based on fluorescence quenching of terbium-danofloxacin (Tb(3+)
      Dano) in the presence of Cfx with maximum excitation and emission wavelengths at
      347 nm and 545 nm, respectively. The quenched fluorescence intensity of Tb(3+)-
      Dano system is proportional to the concentration of Cfx. The optimum conditions
      for the determination of Cfx were studied. RESULTS: The maximum response was
      achieved under optimum conditions of [Tris buffer]= 0.008 mol/l (pH 6.5),
      [Tb(3+)]=1*10(-4) mol/l and [Dano]=1*10(-4) mol/l. The developed method was
      evaluated in terms of accuracy, precision and limit of detection. The linear
      concentration ranges for quantification of Cfx were 8.8*10(-8)-8.8*10(-7) mol/l
      and 1.1*10(-7)-8.8*10(-7) mol/l in standard and human serum samples with the
      detection limits (S/N=3) of 2.8*10(-8) mol/l and 3.9*10(-8) mol/l, respectively.
      The Cfx was determined in pharmaceutical tablets and spiked serum samples and the
      results were satisfactory. CONCLUSION: This method is simple, practical and
      relatively interference-free for determination of Cfx in pharmaceutical tablets
      and serum samples.

PMID- 24904719
TI  - Zataria multiflora increases insulin sensitivity and PPARgamma gene expression in
      high fructose fed insulin resistant rats.
AB  - OBJECTIVES: In insulin resistance, the insulin action in liver, muscles and
      adipocytes decreases and result in hyperglycemia, dyslipidemia and
      hyperinsulinemia. In this study we evaluate the effect of Zataria multiflora
      extract on insulin sensitivity in high fructose fed insulin resistant rats, since
      this extract was shown antihyperglycemic effect in streptozotocin induced
      diabetes in rats. MATERIALS AND METHODS: Experimental rats were fed with high
      fructose diet for 6 weeks and then were treated with Z. multiflora extract or a
      pioglitazone solution for 2 weeks. Blood and tissue samples were collected for
      analysis at the end of two weeks. Blood glucose, serum level of triglyceride and
      cholesterol were measured by auto analyzer. Insulin and adiponectin levels were
      assayed by enzyme-linked immunosorbent assay (ELISA) method. Plasma free fatty
      acids profile was studied by gas chromatography. Peroxisome proliferator
      activated receptor (PPAR.gamma) and Glucose transporter type 4 (GLUT.4) gene
      expressions were assessed by real time polymerase chain reaction (PCR) and
      western blotting. RESULTS: Animals were treated by Z. multiflora extract showed
      insulin (43+/-11pmol/l), adiponectin (5.3+/-0.5 MUg/ml), glucose (144+/-9.8
      mg/dl), and triglyceride (120+/-10 mg/dl) levels significantly improved as
      compare with the control group [insulin (137+/-34 pmol/l), adiponectin (3.9+/
      0.15 MUg/ml), glucose (187+/-15mg/dl), and triglycerides (217+/-18 mg/dl)].
      PPARgamma protein level, also significantly increased in Zataria multiflora
      treated group. CONCLUSION: This study demonstrates the beneficial effects of
      Zataria multiflora extract on insulin resistance in rats fed with a high-fructose
      diet through at least three mechanisms including direct insulin like effect,
      increasing in adiponectin and of PPARgamma protein expression.

PMID- 24904720
TI  - Voluntary and forced exercises prevent the development of tolerance to analgesic
      effects of morphine in rats.
AB  - OBJECTIVES: Morphine is widely used to treat chronic pain. However, its utility
      is hindered by the development of tolerance to its analgesic effects. Despite the
      renowned beneficial effects of physical exercise on cognitive functions and signs
      of morphine withdrawal in morphine-dependent rats, little is known about the
      roles of voluntary and forced exercises in tolerance to analgesic effect of
      morphine in rats. MATERIALS AND METHODS: In this study, rats were injected with
      10 mg/kg of morphine, once daily, SC over a period of 8 days of either voluntary
      or treadmill exercise. Following these injections, the percent of maximum
      possible effect (%MPE) of morphine was measured on the 1(st), 4(th), and 8(th)
      days by hot plate test. RESULTS: Both voluntary and forced exercises
      significantly increased pain threshold compared to the sedentary group (P<0.05).
      Voluntary and forced exercises also significantly increased potency of morphine
      compared to sedentary morphine group (P<0.05). Thus, we concluded that voluntary
      and forced exercises blocked the development of tolerance during 8 daily
      simultaneously treatments. When exercising rats were returned to sedentary
      conditions, sensitivity to the analgesic effects of morphine increased
      significantly and persisted during sedentary period in the exercising rats. In
      other words, %MPE of the exercising morphine-group increased significantly
      compared to saline group (P<0.05). CONCLUSION: Our results showed that voluntary
      and forced exercises may be possible methods for treating the development of
      tolerance to analgesic effect of morphine in rats.

PMID- 24904721
TI  - Immunohistological and electrophysiological characterization of Globose basal
      stem cells.
AB  - OBJECTIVES: In the past few decades, variety of foetal, embryonic and adult stem
      and progenitor cells have been tried with conflicting outcome for cell therapy of
      central nervous system injury and diseases. Cellular characteristics and
      functional plasticity of Globose basal stem cells (GBCs) residing in the
      olfactory epithelium of rat olfactory mucosa have not been studied in the past by
      the neuroscientists due to unavailability of specific markers for GBCs. In the
      present research, we standardized some techniques to isolate GBCs from rat
      olfactory epithelium in pure form using a highly selective GBC-III antibody
      passaged through fluorescence activated cell sorter (FACS). We also characterized
      these cells immunohistologically using various pluripotent stem cell markers.
      This work also throws some light on ionic channels present on these stem cells
      which are responsible for their neuron induction potential. MATERIALS AND
      METHODS: Globose basal stem cells were isolated from rat olfactory epithelium
      using GBC-III antibody and were characterized as multipotent stem cells using
      various neural progenitor markers. Ionic channels on GBCs were studied with
      voltage clamping. RESULTS: GBCs could be isolated in pure (99% purity) form and
      were found to be stained positive for all neural progenitor cell markers. Voltage
      gated Na(+) channels were completely absent, which proves the unexcitable nature
      of GBCs. Leaky K(+) channels were found to be present on the GBC which was of no
      significance. CONCLUSION: This research work can be helpful in understanding the
      nature of these stem cells and utilising them in future as potent candidates for
      neuro-regenerative therapies.

PMID- 24904722
TI  - Effect of normobaric hyperoxia on gentamicin-induced nephrotoxicity in rats.
AB  - OBJECTIVES: Gentamicin sulphate (GS) nephrotoxicity seems to be related to the
      generation of reactive oxygen species. There is evidence that oxygen
      preconditioning increases the activity of antioxidant enzymes. MATERIALS AND
      METHODS: Forty eight female rats were divided into 6 groups (n=8) as follows:
      group 1 was the control, group 2 received daily GS, groups 3,4 and 5 received
      oxygen 2 hr/day for 2 days, 4 hr/day for 2 days, 4 hr/day for 4 days,
      recpectively and then received daily GS, group 6 received oxygen 2 hr/day for 2
      days and then received 2 hr oxygen before daily GS injection. Oxygen (with 90%
      purity) used at the flow rate of 4 l/min. GS administred for 8 days (100 mg/kg,
      IP). Tissue sections prepared from the left kidney, stained with PAS method and
      then studied hisopathologically and stereologically. The right kidneys were
      homogenized and the supernatants were prepared. Serum MDA, creatinine and urea,
      renal MDA, gluthatione and catalase activity were measured. The data were
      analyzed by Mann-Whitney U test at the significant level of P<0.05. RESULTS:
      Oxygen therapy significantly improves serum creatinine and urea, preserve tubular
      volume density, reduce tubular necrosis in groups 4 and 6 compared to group 2.
      Oxygen therapy significantly increases renal catalase in groups 4 and 6 compared
      to group 2. CONCLUSION: Pretreatment with normobaric hyperoxia and daily oxygen
      therapy improved gentamicin nephrotoxicity possibly via inhibition of lipid
      peroxidation and increasing the renal catalase activity but could not restore any
      parameter at the same levels as control group.

PMID- 24904723
TI  - Bilateral ovarian ischemia/reperfusion injury and treatment options in rats with
      an induced model of diabetes.
AB  - OBJECTIVES: This study investigated the effects of melatonin, famotidine,
      mirtazapine, and thiamine pyrophosphate on ischemia/reperfusion (I/R) injury in
      diabetic rats and evaluated oxidant and antioxidant marker measurement results.
      It also examined the effects of the drugs aimed at preventing infertility that
      may result from I/R injury. MATERIALS AND METHODS: Diabetic rats were divided
      into a control group (IRC) to be exposed to I/R, an ovarian I/R + 2.2 mg/kg
      melatonin (IRML) group, an ovarian I/R + famotidine (IRFA) group, an ovarian I/R
      + 20 mg/kg mirtazapine (IRMR) group, an ovarian I/R + 20 mg/kg thiamine
      pyrophosphate (IRTP) group, and a sham operation (SO) group. RESULTS: In the
      control group exposed to I/R, the levels of the oxidant parameters
      Malondialdehyde (MDA) and Myeloperoxidase (MPO) were significantly higher
      compared with the SO group, while the levels of the antioxidant parameters
      glutathione (GSH), Glutathione peroxidase (GPO), Glutathione reductase (GSHRd),
      Glutathione S - transferase (GST), and Superoxide dismutase (SOD) were
      significantly lower. Melatonin, famotidine, mirtazapine, and thiamin
      pyrophosphate prevented a rise in oxidant parameters and a decrease in
      antioxidants in ovarian tissue exposed to I/R. However, apart from thiamin
      pyrophosphate, none of the drugs were able to prevent infertility caused by I/R
      injury. CONCLUSION: Prevention of ovarian I/R injury-related infertility in rats
      with induced diabetes is not through antioxidant activity. Thiamine pyrophosphate
      prevents infertility through an as yet unknown mechanism. This study suggests
      that thiamine pyrophosphate may be useful in the prevention of I/R-related
      infertility in diabetics.

PMID- 24904724
TI  - Evaluation of the effects of paederus beetle extract and gamma irradiation on
      HeLa cells.
AB  - OBJECTIVES: Cervical cancer is a malignancy that is the second most common cause
      of death from cancer in women throughout the world. Paederus beetle (Paederus
      fuscipes) extract (PBE), contains bioactive compounds such as pederine which has
      cytotoxic properties and blocks DNA and protein synthesis at very low
      concentrations. In this investigation we tried to determine the effects co
      treatment with PBE and gamma irradiation on HeLa cells. MATERIALS AND METHODS:
      THE VIABILITY OF THE CELLS WAS MEASURED BY TWO METHODS: MTT and Colony assay.
      RESULTS: We found that supplementing gamma irradiation therapy with PBE does not
      increase cell death and it might even interfere with its cytotoxicty at the
      concentrations below 0.1 ng/ml and the viability for irradiation vs irradiation +
      PBE was 37%: 60%. CONCLUSION: This finding might be due to radioprotective
      effects of the very low doses of PBE against gamma radiation.

PMID- 24904725
TI  - Neuromodulatory role of Bacopa monnieri on oxidative stress induced by postnatal
      exposure to decabromodiphenyl ether (PBDE -209) in neonate and young female mice.
AB  - OBJECTIVES: Bacopa monnieri (BM), a traditional ayurvedic medicine, is a well
      known memory enhancer. We have explored the role of BM against decabrominated
      diphenyl ether (PBDE-209)-induced alterations in neonate and young female mice.
      MATERIALS AND METHODS: Mice were orally administered with B. monnieri at the
      doses of 40, 80 or 120 mg/kg body weight along with PBDE-209 (20 mg/kg body
      weight) from postnatal day (PND) 3-10. Levels of malondialdehyde, protein
      carbonyl and activities of superoxide dismutase and glutathione peroxidase were
      measured at both ages. The correct choices and reference/working memory errors of
      young mice were evaluated by Morris water and radial arm maze. RESULTS: The
      results showed that BM at the dose of 120 mg/kg significantly (P<0.05) restored
      the levels of oxidants and the activities of antioxidant enzymes in frontal
      cortex and hippocampus of neonates against PBDE-209-induced toxicity. CONCLUSION:
      BM plays a neuroprotective role against PBDE-209-induced alterations in oxidative
      status.

PMID- 24904726
TI  - Investigation of the limits of nanoscale filopodial interactions.
AB  - Mesenchymal stem cells are sensitive to changes in feature height, order and
      spacing. We had previously noted that there was an inverse relationship between
      osteoinductive potential and feature height on 15-, 55- and 90 nm-high titania
      nanopillars, with 15 nm-high pillars being the most effective substrate at
      inducing osteogenesis of human mesenchymal stem cells. The osteoinductive effect
      was somewhat diminished by decreasing the feature height to 8 nm, however, which
      suggested that there was a cut-off point, potentially associated with a change in
      cell-nanofeature interactions. To investigate this further, in this study, a
      scanning electron microscopy/three-dimensional scanning electron microscopy
      approach was used to examine the interactions between mesenchymal stem cells and
      the 8 and 15 nm nanopillared surfaces. As expected, the cells adopted a
      predominantly filopodial mode of interaction with the 15 nm-high pillars.
      Interestingly, fine nanoscale membrane projections, which we have termed
      'nanopodia,' were also employed by the cells on the 8 nm pillars, and it seems
      that this is analogous to the cells 'clinging on with their fingertips' to this
      scale of features. 

PMID- 24904727
TI  - In vitro osteoinductive potential of porous monetite for bone tissue engineering.
AB  - Tissue engineering-based bone grafts are emerging as a viable alternative
      treatment modality to repair and regenerate tissues damaged as a result of
      disease or injury. The choice of the biomaterial component is a critical
      determinant of the success of the graft or scaffold; essentially, it must induce
      and allow native tissue integration, and most importantly mimic the hierarchical
      structure of the native bone. Calcium phosphate bioceramics are widely used in
      orthopaedics and dentistry applications due to their similarity to bone mineral
      and their ability to induce a favourable biological response. One such material
      is monetite, which is biocompatible, osteoconductive and has the ability to be
      resorbed under physiological conditions. The osteoinductive properties of
      monetite in vivo are known; however, little is known of the direct effect on
      osteoinduction of human mesenchymal stem cells in vitro. In this study, we
      evaluated the potential of monetite to induce and sustain human mesenchymal stem
      cells towards osteogenic differentiation. Human mesenchymal stem cells were
      seeded on the monetite scaffold in the absence of differentiating factors for up
      to 28 days. The gene expression profile of bone-specific markers in cells on
      monetite scaffold was compared to the control material hydroxyapatite. At day 14,
      we observed a marked increase in alkaline phosphatase, osteocalcin and
      osteonectin expressions. This study provides evidence of a suitable material that
      has potential properties to be used as a tissue engineering scaffold. 

PMID- 24904728
TI  - Cefazolin-loaded mesoporous silicon microparticles show sustained bactericidal
      effect against Staphylococcus aureus.
AB  - Cefazolin is an antibiotic frequently used in preoperative prophylaxis of
      orthopedic surgery and to fight secondary infections post-operatively. Although
      its systemic delivery in a bulk or bolus dose is usually effective, the local and
      controlled release can increase its effectiveness by lowering dosages, minimizing
      total drug exposure, abating the development of antibiotic resistance and
      avoiding the cytotoxic effect. A delivery system based on mesoporous silicon
      microparticles was developed that is capable of efficiently loading and
      continuously releasing cefazolin over several days. The in vitro release kinetics
      from mesoporous silicon microparticles with three different nanopore sizes was
      evaluated, and minimal inhibitory concentration of cefazolin necessary to
      eliminate a culture of Staphylococcus aureus was identified to be 250 ug/mL. A
      milder toxicity toward mesenchymal stem cells was observed from mesoporous
      silicon microparticles over a 7-day period. Medium pore size-loaded mesoporous
      silicon microparticles exhibited long-lasting bactericidal properties in a zone
      inhibition assay while they were able to kill all the bacteria growing in
      suspension cultures within 24 h. This study demonstrates that the sustained
      release of cefazolin from mesoporous silicon microparticles provides immediate
      and long-term control over bacterial growth both in suspension and adhesion while
      causing minimal toxicity to a population of mesenchymal stem cell. Mesoporous
      silicon microparticles offer significant advantageous properties for drug
      delivery applications in tissue engineering as it favorably extends drug
      bioavailability and stability, while reducing concomitant cytotoxicity to the
      surrounding tissues. 

PMID- 24904729
TI  - Combined decellularisation and dehydration improves the mechanical properties of
      tissue-engineered sinews.
AB  - Novel sources of replacement sinews are needed to repair damaged tissue after
      injury. The current methods of repair ultilise autografts, allografts or
      xenografts, although each method has distinct disadvantages that limit their
      success. Decellularisation of harvested tissues has been previously investigated
      for sinew repair with the long-term aim of repopulating the structure with
      autologous cells. Although this procedure shows promise, the demand for donor
      scaffolds will always outweigh supply. Here, we report the fabrication of fibrin
      based tissue-engineered sinews, which can be decellularised, dehydrated and
      stored. The sinews may then be rehydrated and repopulated with an autologous cell
      population. In addition to enabling production of patient-specific implants,
      interestingly, the process of combined decellularisation, dehydration and
      rehydration enhanced the mechanical properties of the sinew. The treated sinews
      exhibited a 2.6-fold increase in maximum load and 8-fold increase in ultimate
      tensile strength when compared with the control group (p < 0.05 in both cases). 

PMID- 24904730
TI  - Calcium phosphate thin films enhance the response of human mesenchymal stem cells
      to nanostructured titanium surfaces.
AB  - The development of biomaterial surfaces possessing the topographical cues that
      can promote mesenchymal stem cell recruitment and, in particular, those capable
      of subsequently directing osteogenic differentiation is of increasing importance
      for the advancement of tissue engineering. While it is accepted that it is the
      interaction with specific nanoscale topography that induces mesenchymal stem cell
      differentiation, the potential for an attendant bioactive chemistry working in
      tandem with such nanoscale features to enhance this effect has not been
      considered to any great extent. This article presents a study of mesenchymal stem
      cell response to conformal bioactive calcium phosphate thin films sputter
      deposited onto a polycrystalline titanium nanostructured surface with proven
      capability to directly induce osteogenic differentiation in human bone marrow
      derived mesenchymal stem cells. The sputter deposited surfaces supported high
      levels of human bone marrow-derived mesenchymal stem cell adherence and
      proliferation, as determined by DNA quantification. Furthermore, they were also
      found to be capable of directly promoting significant levels of osteogenic
      differentiation. Specifically, alkaline phosphatase activity, gene expression and
      immunocytochemical localisation of key osteogenic markers revealed that the
      nanostructured titanium surfaces and the bioactive calcium phosphate coatings
      could direct the differentiation towards an osteogenic lineage. Moreover, the
      addition of the calcium phosphate chemistry to the topographical profile of the
      titanium was found to induce increased human bone marrow-derived mesenchymal stem
      cell differentiation compared to that observed for either the titanium or calcium
      phosphate coating without an underlying nanostructure. Hence, the results
      presented here highlight that a clear benefit can be achieved from a surface
      engineering strategy that combines a defined surface topography with an
      attendant, conformal bioactive chemistry to enhance the direct osteogenic
      differentiation of human bone marrow-derived mesenchymal stem cells. 

PMID- 24904731
TI  - GenderMedDB: an interactive database of sex and gender-specific medical
      literature.
AB  - BACKGROUND: Searches for sex and gender-specific publications are complicated by
      the absence of a specific algorithm within search engines and by the lack of
      adequate archives to collect the retrieved results. We previously addressed this
      issue by initiating the first systematic archive of medical literature containing
      sex and/or gender-specific analyses. This initial collection has now been greatly
      enlarged and re-organized as a free user-friendly database with multiple
      functions: GenderMedDB (http://gendermeddb.charite.de). DESCRIPTION: GenderMedDB
      retrieves the included publications from the PubMed database. Manuscripts
      containing sex and/or gender-specific analysis are continuously screened and the
      relevant findings organized systematically into disciplines and diseases.
      Publications are furthermore classified by research type, subject and participant
      numbers. More than 11,000 abstracts are currently included in the database, after
      screening more than 40,000 publications. The main functions of the database
      include searches by publication data or content analysis based on pre-defined
      classifications. In addition, registrants are enabled to upload relevant
      publications, access descriptive publication statistics and interact in an open
      user forum. CONCLUSIONS: Overall, GenderMedDB offers the advantages of a
      discipline-specific search engine as well as the functions of a participative
      tool for the gender medicine community.

PMID- 24904732
TI  - A computational model for the formation of lamin-B mitotic spindle envelope and
      matrix.
AB  - Recent reports show that, after nuclear envelope breakdown, lamin-B, a component
      of the nuclear lamina in interphase, localizes around the mitotic spindle as a
      membranous network. How this process occurs, however, and how it influences
      mitotic spindle morphogenesis is unclear. Here, we develop a computational model
      based on a continuum description to represent the abundance and location of
      various molecular species involved during mitosis, and use the model to test a
      number of hypotheses regarding the formation of the mitotic matrix. Our model
      illustrates that freely diffusible nuclear proteins can be captured and
      transported to the spindle poles by minus-end-directed microtubule (MT) motors.
      Moreover, simulations show that these proteins can be used to build a shell-like
      region that envelopes the mitotic spindle, which helps to improve the focusing of
      the mitotic spindle by spatially restricting MT polymerization and limiting the
      effective diffusion of the free MTs. Simulations also confirm that spatially
      dependent regulation of the spindle network through the Ran system improves
      spindle focusing and morphology. Our results agree with experimental observations
      that lamin-B reorganizes around the spindle and helps to maintain spindle
      morphology. 

PMID- 24904733
TI  - Quantitative implementation of the endogenous molecular-cellular network
      hypothesis in hepatocellular carcinoma.
AB  - A quantitative hypothesis for cancer genesis and progression-the endogenous
      molecular-cellular network hypothesis, intended to include both genetic and
      epigenetic causes of cancer-has been proposed recently. Using this hypothesis,
      here we address the molecular basis for maintaining normal liver and
      hepatocellular carcinoma (HCC), and the potential strategy to cure or relieve
      HCC. First, we elaborate the basic assumptions of the hypothesis and establish a
      core working network of HCC according to the hypothesis. Second, we quantify the
      working network by a nonlinear dynamical system. We show that the working network
      reproduces the main known features of normal liver and HCC at both the modular
      and molecular levels. Lastly, the validated working network reveals that (i)
      specific positive feedback loops are responsible for the maintenance of normal
      liver and HCC; (ii) inhibiting proliferation and inflammation-related positive
      feedback loops and simultaneously inducing a liver-specific positive feedback
      loop is predicated as a potential strategy to cure or relieve HCC; and (iii) the
      genesis and regression of HCC are asymmetric. In light of the characteristic
      properties of the nonlinear dynamical system, we demonstrate that positive
      feedback loops must exist as a simple and general molecular basis for the
      maintenance of heritable phenotypes, such as normal liver and HCC, and regulating
      the positive feedback loops directly or indirectly provides potential strategies
      to cure or relieve HCC. 

PMID- 24904734
TI  - Epigenetic state network approach for describing cell phenotypic transitions.
AB  - Recent breakthroughs of cell phenotype reprogramming impose theoretical
      challenges on unravelling the complexity of large circuits maintaining cell
      phenotypes coupled at many different epigenetic and gene regulation levels, and
      quantitatively describing the phenotypic transition dynamics. A popular picture
      proposed by Waddington views cell differentiation as a ball sliding down a
      landscape with valleys corresponding to different cell types separated by ridges.
      Based on theories of dynamical systems, we establish a novel 'epigenetic state
      network' framework that captures the global architecture of cell phenotypes,
      which allows us to translate the metaphorical low-dimensional Waddington
      epigenetic landscape concept into a simple-yet-predictive rigorous mathematical
      framework of cell phenotypic transitions. Specifically, we simplify a high
      dimensional epigenetic landscape into a collection of discrete states
      corresponding to stable cell phenotypes connected by optimal transition pathways
      among them. We then apply the approach to the phenotypic transition processes
      among fibroblasts (FBs), pluripotent stem cells (PSCs) and cardiomyocytes (CMs).
      The epigenetic state network for this case predicts three major transition
      pathways connecting FBs and CMs. One goes by way of PSCs. The other two pathways
      involve transdifferentiation either indirectly through cardiac progenitor cells
      or directly from FB to CM. The predicted pathways and multiple intermediate
      states are supported by existing microarray data and other experiments. Our
      approach provides a theoretical framework for studying cell phenotypic
      transitions. Future studies at single-cell levels can directly test the model
      predictions. 

PMID- 24904735
TI  - Control of cell growth, division and death: information processing in living
      cells.
AB  - By way of surface receptor molecules and internal surveillance mechanisms, the
      living cell receives information about its external environment and internal
      state. In light of this information, the cell must determine its most appropriate
      course of action under the circumstances and initiate the relevant response
      pathways. Typical responses include growth and division, sexual reproduction,
      movement, differentiation and programmed cell death. Similar to a digital
      computer that uses bistable electrical switches to store and process information,
      the living cell uses bistable biochemical switches to implement its decision
      making capabilities. In this review article, we describe some of the lines of
      thought that led, over the last 50 years, to our current understanding of
      cellular information processing, particularly related to cell growth, division
      and death. 

PMID- 24904736
TI  - Modelling chromosome dynamics in mitosis: a historical perspective on models of
      metaphase and anaphase in eukaryotic cells.
AB  - Mitosis is the process by which the genome is segregated to form two identical
      daughter cells during cell division. The process of cell division is essential to
      the maintenance of every form of life. However, a detailed quantitative
      understanding of mitosis has been difficult owing to the complexity of the
      process. Indeed, it has been long recognized that, because of the complexity of
      the molecules involved, their dynamics and their properties, the mitotic events
      that mediate the segregation of the genome into daughter nuclei cannot be fully
      understood without the contribution of mathematical/quantitative modelling. Here,
      we provide an overview of mitosis and describe the dynamic and mechanical
      properties of the mitotic apparatus. We then discuss several quantitative models
      that emerged in the past decades and made an impact on our understanding of
      specific aspects of mitosis, including the motility of the chromosomes within the
      mitotic spindle during metaphase and anaphase, the maintenance of spindle length
      during metaphase and the switch to spindle elongation that occurs during
      anaphase. 

PMID- 24904738
TI  - The balance between cell cycle arrest and cell proliferation: control by the
      extracellular matrix and by contact inhibition.
AB  - To understand the dynamics of the cell cycle, we need to characterize the balance
      between cell cycle arrest and cell proliferation, which is often deregulated in
      cancers. We address this issue by means of a detailed computational model for the
      network of cyclin-dependent kinases (Cdks) driving the mammalian cell cycle.
      Previous analysis of the model focused on how this balance is controlled by
      growth factors (GFs) or the levels of activators (oncogenes) and inhibitors
      (tumour suppressors) of cell cycle progression. Supra-threshold changes in the
      level of any of these factors can trigger a switch in the dynamical behaviour of
      the Cdk network corresponding to a bifurcation between a stable steady state,
      associated with cell cycle arrest, and sustained oscillations of the various
      cyclin/Cdk complexes, corresponding to cell proliferation. Here, we focus on the
      regulation of cell proliferation by cellular environmental factors external to
      the Cdk network, such as the extracellular matrix (ECM), and contact inhibition,
      which increases with cell density. We extend the model for the Cdk network by
      including the phenomenological effect of both the ECM, which controls the
      activation of the focal adhesion kinase (FAK) that promotes cell cycle
      progression, and cell density, which inhibits cell proliferation via the
      Hippo/YAP pathway. The model shows that GFs and FAK activation are capable of
      triggering in a similar dynamical manner the transition to cell proliferation,
      while the Hippo/YAP pathway can arrest proliferation once cell density passes a
      critical threshold. The results account for the dependence or independence of
      cell proliferation on serum and/or cell anchorage to ECM. Whether the balance in
      the Cdk network is tilted towards cell cycle arrest or proliferation depends on
      the direction in which the threshold associated with the bifurcation is passed
      once the cell integrates the multiple, internal or external signals that promote
      or impede progression in the cell cycle. 

PMID- 24904737
TI  - Modelling mammalian cellular quiescence.
AB  - Cellular quiescence is a reversible non-proliferating state. The reactivation of
      'sleep-like' quiescent cells (e.g. fibroblasts, lymphocytes and stem cells) into
      proliferation is crucial for tissue repair and regeneration and a key to the
      growth, development and health of higher multicellular organisms, such as
      mammals. Quiescence has been a primarily phenotypic description (i.e. non
      permanent cell cycle arrest) and poorly studied. However, contrary to the earlier
      thinking that quiescence is simply a passive and dormant state lacking
      proliferating activities, recent studies have revealed that cellular quiescence
      is actively maintained in the cell and that it corresponds to a collection of
      heterogeneous states. Recent modelling and experimental work have suggested that
      an Rb-E2F bistable switch plays a pivotal role in controlling the quiescence
      proliferation balance and the heterogeneous quiescent states. Other quiescence
      regulatory activities may crosstalk with and impinge upon the Rb-E2F bistable
      switch, forming a gene network that controls the cells' quiescent states and
      their dynamic transitions to proliferation in response to noisy environmental
      signals. Elucidating the dynamic control mechanisms underlying quiescence may
      lead to novel therapeutic strategies that re-establish normal quiescent states,
      in a variety of hyper- and hypo-proliferative diseases, including cancer and
      ageing. 

PMID- 24904740
TI  - A queueing approach to multi-site enzyme kinetics.
AB  - Multi-site enzymes, defined as where multiple substrate molecules can bind
      simultaneously to the same enzyme molecule, play a key role in a number of
      biological networks, with the Escherichia coli protease ClpXP a well-studied
      example. These enzymes can form a low latency 'waiting line' of substrate to the
      enzyme's catalytic core, such that the enzyme molecule can continue to collect
      substrate even when the catalytic core is occupied. To understand multi-site
      enzyme kinetics, we study a discrete stochastic model that includes a single
      catalytic core fed by a fixed number of substrate binding sites. A natural
      queueing systems analogy is found to provide substantial insight into the
      dynamics of the model. From this, we derive exact results for the probability
      distribution of the enzyme configuration and for the distribution of substrate
      departure times in the case of identical but distinguishable classes of substrate
      molecules. Comments are also provided for the case when different classes of
      substrate molecules are not processed identically. 

PMID- 24904739
TI  - It is not the parts, but how they interact that determines the behaviour of
      circadian rhythms across scales and organisms.
AB  - Biological rhythms, generated by feedback loops containing interacting genes,
      proteins and/or cells, time physiological processes in many organisms. While many
      of the components of the systems that generate biological rhythms have been
      identified, much less is known about the details of their interactions. Using
      examples from the circadian (daily) clock in three organisms, Neurospora,
      Drosophila and mouse, we show, with mathematical models of varying complexity,
      how interactions among (i) promoter sites, (ii) proteins forming complexes, and
      (iii) cells can have a drastic effect on timekeeping. Inspired by the
      identification of many transcription factors, for example as involved in the
      Neurospora circadian clock, that can both activate and repress, we show how these
      multiple actions can cause complex oscillatory patterns in a transcription
      translation feedback loop (TTFL). Inspired by the timekeeping complex formed by
      the NMO-PER-TIM-SGG complex that regulates the negative TTFL in the Drosophila
      circadian clock, we show how the mechanism of complex formation can determine the
      prevalence of oscillations in a TTFL. Finally, we note that most mathematical
      models of intracellular clocks model a single cell, but compare with experimental
      data from collections of cells. We find that refitting the most detailed model of
      the mammalian circadian clock, so that the coupling between cells matches
      experimental data, yields different dynamics and makes an interesting prediction
      that also matches experimental data: individual cells are bistable, and network
      coupling removes this bistability and causes the network to be more robust to
      external perturbations. Taken together, we propose that the interactions between
      components in biological timekeeping systems are carefully tuned towards proper
      function. We also show how timekeeping can be controlled by novel mechanisms at
      different levels of organization. 

PMID- 24904742
TI  - Protein phosphatase 4 is an essential positive regulator for Treg development,
      function, and protective gut immunity.
AB  - BACKGROUND: Protein phosphates 4 (PP4), encoded by the ppp4c gene, is a
      ubiquitously expressed phosphatase that has been implicated in the regulation of
      cytokine signaling and lymphocyte survival; recent reports suggest that PP4 may
      be involved in pre-TCR signaling and B cell development. However, whether PP4
      also modulates the functions of peripheral T cells has not been investigated due
      to the lack of a suitable in vivo model. Treg cells are a specialized subset of
      CD4 helper T cells that can suppress the proliferation of activated effector T
      cells. In the absence of this negative regulation, autoimmune syndromes and
      inflammatory diseases, such as human Crohn's disease, will arise. RESULTS: In
      this report, we generated mice with T cell-specific ablation of the ppp4c gene
      (CD4cre:PP4(f/f)) and a Foxp3-GFP reporter gene to examine the roles of PP4 in
      Treg development and function. Characterizations of the CD4cre:PP4(f/f) mice
      showed that PP4 deficiency induced partial alphabeta T lymphopenia and T cell
      hypo-proliferation. Further analyses revealed significant reductions in the
      numbers of thymic and peripheral Treg cells, as well as in the efficiency of in
      vitro Treg polarization. In addition, PP4-deficient Treg cells exhibited reduced
      suppressor functions that were associated with decreased IL-10, CTLA4, GITR and
      CD103 expression. More interestingly, the CD4cre:PP4(f/f) mice developed
      spontaneous rectal prolapse and colitis with symptoms similar to human Crohn's
      disease. The pathogenesis of colitis required the presence of commensal bacteria,
      and was correlated with reduced Treg cells in the gut. Nevertheless, PP4
      deficient Treg cells were still capable of suppressing experimental colitis,
      suggesting that multiple factors contributed to the onset of the spontaneous
      colitis. CONCLUSIONS: While the molecular mechanisms remain to be investigated,
      our results clearly show that PP4 plays a non-redundant role for the
      differentiation, suppressor activity and gut homeostasis of Treg cells. The onset
      of spontaneous colitis in the CD4cre:PP4(f/f) mice further suggests that PP4 is
      essential for the maintenance of protective gut immunity. The CD4cre:PP4(f/f)
      mice thus may serve as a good model for studying the interactions between Treg
      cells and gut commensal bacteria for the regulation of mucosal immunity.

PMID- 24904743
TI  - Autophagy protects against palmitate-induced apoptosis in hepatocytes.
AB  - BACKGROUND: Non-alcoholic fatty liver disease, one of the most common liver
      diseases, has obtained increasing attention. Palmitate (PA)-induced liver injury
      is considered a risk factor for the development of non-alcoholic fatty liver
      disease. Autophagy, a cellular degradative pathway, is an important self-defense
      mechanism in response to various stresses. In this study, we investigated whether
      autophagy plays a protective role in the progression of PA-induced hepatocytes
      injury. RESULTS: Annexin V-FITC/PI staining by FCM analysis, TUNEL assay and the
      detection of PARP and cleaved caspase3 expression levels demonstrated that PA
      treatment prominently induced the apoptosis of hepatocytes. Meanwhile, treatment
      of PA strongly induced the formation of GFP-LC3 dots, the conversion from LC3I to
      LC3II, the decrease of p62 protein levels and the increase of autophagosomes.
      These results indicated that PA also induced autophagy activation. Autophagy
      inhibition through chloroquine pretreatment or Atg5shRNA infection led to the
      increase of cell apoptosis after PA treatment. Moreover, induction of autophagy
      by pretreatment with rapamycin resulted in distinct decrease of PA-induced
      apoptosis. Therefore, autophagy can prevent hepatocytes from PA-induced
      apoptosis. In the further study, we explored pathway of autophagy activation in
      PA-treated hepatocytes. We found that PA activated PKCalpha in hepatocytes, and
      had no influence on mammalian target of rapamycin and endoplasmic reticulum
      stress pathways. CONCLUSIONS: These results demonstrated that autophagy plays a
      protective role in PA-induced hepatocytes apoptosis. And PA might induce
      autophagy through activating PKCalpha pathway in hepatocytes.

PMID- 24904745
TI  - How can medical schools contribute to bringing about health equity?
AB  - The role of medical schools is in a process of change. The World Health
      Organization has declared that they can no longer be ivory towers whose primary
      focus is the production of specialist physicians and cutting edge laboratory
      research. They must also be socially accountable and direct their activities
      towards meeting the priority health concerns of the areas they serve. The agenda
      must be set in partnership with stakeholders including governments, health care
      organisations and the public. The concept of social accountability has particular
      resonance for the Bar Ilan Faculty of Medicine in the Galilee, Israel's newest
      medical school, which was established with a purpose of reducing health
      inequities in the Region. As a way of exploring and understanding the issues,
      discussions were held with international experts in the field who visited the
      Galilee. A symposium involving representatives from other medical schools in
      Israel was also held to extend the discourse. Deliberations that took place are
      reported here. The meaning of social accountability was discussed, and how it
      could be achieved. Three forms of action were the principal foci - augmentation
      of the medical curriculum, direct action through community engagement and
      political advocacy. A platform was set for taking the social accountability
      agenda forward, with the hope that it will impact on health inequalities in
      Israel and contribute to discussions elsewhere. 

PMID- 24904744
TI  - Transcriptional and epigenetic regulation of PPARgamma expression during
      adipogenesis.
AB  - The nuclear receptor PPARgamma is a master regulator of adipogenesis. PPARgamma
      is highly expressed in adipose tissues and its expression is markedly induced
      during adipogenesis. In this review, we describe the current knowledge, as well
      as future directions, on transcriptional and epigenetic regulation of PPARgamma
      expression during adipogenesis. Investigating the molecular mechanisms that
      control PPARgamma expression during adipogenesis is critical for understanding
      the development of white and brown adipose tissues, as well as pathological
      conditions such as obesity and diabetes. The robust induction of PPARgamma
      expression during adipogenesis also serves as an excellent model system for
      studying transcriptional and epigenetic regulation of cell-type-specific gene
      expression. 

PMID- 24904746
TI  - Introducing an osteopathic approach into neonatology ward: the NE-O model.
AB  - BACKGROUND: Several studies showed the effect of osteopathic manipulative
      treatment on neonatal care in reducing length of stay in hospital,
      gastrointestinal problems, clubfoot complications and improving cranial asymmetry
      of infants affected by plagiocephaly. Despite several results obtained, there is
      still a lack of standardized osteopathic evaluation and treatment procedures for
      newborns recovered in neonatal intensive care unit (NICU). The aim of this paper
      is to suggest a protocol on osteopathic approach (NE-O model) in treating
      hospitalized newborns. METHODS: The NE-O model is composed by specific evaluation
      tests and treatments to tailor osteopathic method according to preterm and term
      infants' needs, NICU environment, medical and paramedical assistance. This model
      was developed to maximize the effectiveness and the clinical use of osteopathy
      into NICU. RESULTS: The NE-O model was adopted in 2006 to evaluate the efficacy
      of OMT in neonatology. Results from research showed the effectiveness of this
      osteopathic model in reducing preterms' length of stay and hospital costs.
      Additionally the present model was demonstrated to be safe. CONCLUSION: The
      present paper defines the key steps for a rigorous and effective osteopathic
      approach into NICU setting, providing a scientific and methodological example of
      integrated medicine and complex intervention.

PMID- 24904747
TI  - Mapping intended spinal site of care from the upright to prone position: an
      interexaminer reliability study.
AB  - BACKGROUND: Upright examination procedures like radiology, thermography, manual
      muscle testing, and spinal motion palpation may lead to spinal interventions with
      the patient prone. The reliability and accuracy of mapping upright examination
      findings to the prone position is unknown. This study had 2 primary goals: (1)
      investigate how erroneous spine-scapular landmark associations may lead to errors
      in treating and charting spine levels; and (2) study the interexaminer
      reliability of a novel method for mapping upright spinal sites to the prone
      position. METHODS: Experiment 1 was a thought experiment exploring the
      consequences of depending on the erroneous landmark association of the inferior
      scapular tip with the T7 spinous process upright and T6 spinous process prone
      (relatively recent studies suggest these levels are T8 and T9, respectively).
      This allowed deduction of targeting and charting errors. In experiment 2, 10
      examiners (2 experienced, 8 novice) used an index finger to maintain contact with
      a mid-thoracic spinous process as each of 2 participants slowly moved from the
      upright to the prone position. Interexaminer reliability was assessed by
      computing Intraclass Correlation Coefficient, standard error of the mean, root
      mean squared error, and the absolute value of the mean difference for each
      examiner from the 10 examiner mean for each of the 2 participants. RESULTS: The
      thought experiment suggesting that using the (inaccurate) scapular tip landmark
      rule would result in a 3 level targeting and charting error when radiological
      findings are mapped to the prone position. Physical upright exam procedures like
      motion palpation would result in a 2 level targeting error for intervention, and
      a 3 level error for charting. The reliability experiment showed examiners
      accurately maintained contact with the same thoracic spinous process as the
      participant went from upright to prone, ICC (2,1) = 0.83. CONCLUSIONS: As manual
      therapists, the authors have emphasized how targeting errors may impact upon
      manual care of the spine. Practitioners in other fields that need to accurately
      locate spinal levels, such as acupuncture and anesthesiology, would also be
      expected to draw important conclusions from these findings.

PMID- 24904748
TI  - Spinal manipulation and exercise for low back pain in adolescents: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Low back pain is among the most common and costly chronic health care
      conditions. Recent research has highlighted the common occurrence of non-specific
      low back pain in adolescents, with prevalence estimates similar to adults. While
      multiple clinical trials have examined the effectiveness of commonly used
      therapies for the management of low back pain in adults, few trials have
      addressed the condition in adolescents. The purpose of this paper is to describe
      the methodology of a randomized clinical trial examining the effectiveness of
      exercise with and without spinal manipulative therapy for chronic or recurrent
      low back pain in adolescents. METHODS/DESIGN: This study is a randomized
      controlled trial comparing twelve weeks of exercise therapy combined with spinal
      manipulation to exercise therapy alone. Beginning in March 2010, a total of 184
      participants, ages 12 to 18, with chronic or recurrent low back pain are enrolled
      across two sites. The primary outcome is self-reported low back pain intensity.
      Other outcomes include disability, quality of life, improvement, satisfaction,
      activity level, low back strength, endurance, and motion. Qualitative interviews
      are conducted to evaluate participants' perceptions of treatment. DISCUSSION:
      This is the first randomized clinical trial assessing the effectiveness of
      combining spinal manipulative therapy with exercise for adolescents with low back
      pain. The results of this study will provide important evidence on the role of
      these conservative treatments for the management of low back pain in adolescents.
      TRIAL REGISTRATION: (ClinicalTrials.gov NCT01096628).

PMID- 24904749
TI  - Learning from myocarditis: mimicry, chaos and black holes.
AB  - Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes
      of heart failure, especially in children and young adults. We have developed
      animal models to investigate their pathogenesis by infecting genetically
      susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin
      or its immunodominant peptide. A number of valuable lessons have emerged from our
      study of this paradigm of an infection-induced autoimmune disease. We understand
      more clearly how natural autoimmunity, as an important component of normal
      physiology, must be recalibrated regularly due to changes caused by infection or
      other internal and external stimuli. A new normal homeostatic platform will be
      established based on its evolutionary fitness. A loss of homeostasis with out-of
      control normal autoimmunity leads to autoimmune disease. It is signified early on
      by a spread of an adaptive autoimmune response to novel epitopes and neighboring
      antigens. The progression from infection to normal, well-balanced autoimmunity to
      autoimmune disease and on to irreversible damage is a complex, step-wise process.
      Yet, chaos theory provides hope that the pattern is potentially predictable.
      Infection-induced autoimmune disease represents a sequence of events heading for
      a train wreck at the end of the line. Our aim in autoimmune disease research must
      be to stop the train before this happens. 

PMID- 24904750
TI  - Recovery of the failing heart: emerging approaches and mechanisms in excitation
      contraction coupling.
AB  - Heart failure (HF) is a growing cause of morbidity and mortality globally. All
      clinical therapies that reduce mortality have been shown to induce reverse
      remodeling. In this article, we discuss a conceptual approach to the evolving
      treatment of HF using emerging treatment modalities for the drug-refractory
      patient. This approach is based on the combinatorial, integrated application of
      therapies shown to influence reverse remodeling in the laboratory. 

PMID- 24904751
TI  - Perivascular adipose tissue contains functional catecholamines.
AB  - The sympathetic nervous system and its neurotransmitter effectors are undeniably
      important to blood pressure control. We made the novel discovery that
      perivascular adipose tissue (PVAT) contains significant concentrations of
      catecholamines. We hypothesized that PVAT contains sufficient releasable
      catecholamines to affect vascular function. HPLC, isometric contractility,
      immunohistochemistry, whole animal approaches and pharmacology were used to test
      this hypothesis. In normal rat thoracic aorta and superior mesenteric artery, the
      indirect sympathomimetic tyramine caused a concentration-dependent contraction
      that was dependent on the presence of PVAT. Tyramine stimulated release of NA,
      dopamine (DA) and the tryptamine serotonin (5-HT) from PVAT isolated from both
      arteries. In both arteries, tyramine-induced concentration-dependent contraction
      was rightward-shifted and reduced by the noradrenaline transporter inhibitor
      nisoxetine (1 MUM), the vesicular monoamine transporter tetrabenazine (10 MUM)
      and abolished by the alpha adrenoreceptor antagonist prazosin (100 nM).
      Inhibitors of the DA and 5-HT transporter did not alter tyramine-induced, PVAT
      dependent contraction. Removal of the celiac ganglion as a neuronal source of
      catecholamines for superior mesenteric artery PVAT did not significantly reduce
      the maximum or shift the concentration dependent contraction to tyramine.
      Electrical field stimulation of the isolated aorta was not affected by the
      presence of PVAT. These data suggest that PVAT components that are independent of
      sympathetic nerves can release NA in a tyramine-sensitive manner to result in
      arterial contraction. Because PVAT is intimately apposed to the artery, this
      raises the possibility of local control of arterial function by PVAT
      catecholamines.

PMID- 24904752
TI  - Sleep quality and general health status of employees exposed to extremely low
      frequency magnetic fields in a petrochemical complex.
AB  - BACKGROUND: Advances in science and technology of electrical equipment, despite
      increasing human welfare in everyday life, have increased the number of people
      exposed to Electro-Magnetic Fields (EMFs). Because of possible adverse effects on
      the health of exposed individuals, the EMFs have being the center of attention.
      This study was performed to determine possible correlation between Extremely Low
      Frequency Electro-Magnetic Fields (ELF EMFs) and sleep quality and public health
      of those working in substation units of a petrochemical complex in southern Iran.
      MATERIALS AND METHOD: To begin with, magnetic flux density was measured at
      different parts of a Control Building and two substations in accordance with IEEE
      std 644-1994. Subsequently, the questionnaires "Pittsburgh Sleep Quality Index"
      (PSQI) and "General Health Quality (GHQ)" were used to investigate relationship
      between ELF exposure level and sleep quality and public health, respectively.
      Both questionnaires were placed at disposal of a total number of 40 workers at
      the complex. The filled out questionnaires were analyzed by T-test, Duncan and
      the Chi-square tests. RESULTS: The obtained results revealed that 28% of those in
      case group suffered from poor health status and 61% were diagnosed with a sleep
      disorder. However, all members in control group were in good health condition and
      only 4.5% of them had undesirable sleep quality. CONCLUSION: In spite of a
      significant difference between the case and control groups in terms of sleep
      quality and general health, no significant relationship was found between the
      exposure level and sleep quality and general health. It is worth noting that the
      measured EMF values were lower than the standard limits recommended by American
      Conference of Industrial Hygienists (ACGIH). However, given the uncertainties
      about the pathogenic effects caused by exposure to ELF EMFs, further
      epidemiological studies and periodic testing of personnel working in high voltage
      substations are of utmost importance.

PMID- 24904753
TI  - Retracted: Therapeutic management of the hallux rigidus.

PMID- 24904754
TI  - T cell immunosenescence, hypertension, and arterial stiffness.

PMID- 24904755
TI  - Multi-marker Solid Tumor Panels Using Next-generation Sequencing to Direct
      Molecularly Targeted Therapies.
AB  - In contemporary oncology practices there is an increasing emphasis on concurrent
      evaluation of multiple genomic alterations within the biological pathways driving
      tumorigenesis. At the foundation of this paradigm shift are several commercially
      available tumor panels using next-generation sequencing to develop a more
      complete molecular blueprint of the tumor. Ideally, these would be used to
      identify clinically actionable variants that can be matched with available
      molecularly targeted therapy, regardless of the tumor site or histology.
      Currently, there is little information available on the post-analytic processes
      unique to next-generation sequencing platforms used by the companies offering
      these tests. Additionally, evidence of clinical validity showing an association
      between the genetic markers curated in these tests with treatment response to
      approved molecularly targeted therapies is lacking across all solid-tumor types.
      To date, there is no published data of improved outcomes when using the
      commercially available tests to guide treatment decisions. The uniqueness of
      these tests from other genomic applications used to guide clinical treatment
      decisions lie in the sequencing platforms used to generate large amounts of
      genomic data, which have their own related issues regarding analytic and clinical
      validity, necessary precursors to the evaluation of clinical utility. The
      generation and interpretation of these data will require new evidentiary
      standards for establishing not only clinical utility, but also analytical and
      clinical validity for this emerging paradigm in oncology practice. 

PMID- 24904756
TI  - Cohesin mutations in myeloid malignancies: underlying mechanisms.
AB  - Recently, whole genome sequencing approaches have pinpointed mutations in genes
      that were previously not associated with cancer. For Acute Myeloid Leukaemia
      (AML), and other myeloid disorders, these approaches revealed a high prevalence
      of mutations in genes encoding the chromosome cohesion complex, cohesin. Cohesin
      mutations represent a novel genetic pathway for AML, but how AML arises from
      these mutations is unknown. This review will explore the potential mechanisms by
      which cohesin mutations contribute to AML and other myeloid malignancies. 

PMID- 24904757
TI  - Treatment of Gambling Disorders.
AB  - Preclinical and clinical research implicate several neurotransmitter systems in
      the pathophysiology of gambling disorder (GD). In particular, neurobiological
      research suggests alterations in serotonergic, dopaminergic, glutamatergic and
      opioidergic functioning. The relative efficacy of medications targeting these
      systems remains a topic of ongoing research, and there is currently no Food and
      Drug Administration (FDA) approved medication with an indication for GD.
      Considering co-occurring disorders may be particularly important when devising a
      treatment plan for GD: extant data suggest that the opioid antagonist naltrexone
      may by the most effective form of current pharmacotherapy for GD, particularly
      for individuals with a co-occurring substance-use disorder (SUD) or with a family
      history of alcoholism. In contrast, lithium or other mood stabilizers may be most
      effective for GD for patients presenting with a co-occurring bipolar-spectrum
      disorder (BSD). Further, serotonin reuptake inhibitors (SRIs) may be efficacious
      in reducing GD symptoms for individuals also presenting with a (non-BSD) mood or
      anxiety disorder. Finally, elevated rates of GD (and other Impulse Control
      Disorders; ICDs) have been noted among individuals with Parkinson's Disease (PD),
      and clinicians should assess for vulnerability to GD when considering treatment
      options for PD. Reducing levodopa or dopamine agonist (DA) dosages may partially
      reduce GD symptoms among patients with co-occurring PD. For GD patients not
      willing to consider drug treatment, n-acetyl cysteine or behavioral therapies may
      be effective. Ongoing research into the effectiveness of combined behavioral and
      pharmacotherapies is being conducted; thus combined treatments should also be
      considered.

PMID- 24904758
TI  - Molecular patterns of multidrug resistance of Mycobacterium tuberculosis in
      Georgia.
AB  - BACKGROUND: Tuberculosis (TB) infections caused by multidrug-resistant
      Mycobacterium tuberculosis (MDR MTB) remain a significant public health concern
      worldwide. Georgia has a high prevalence of MDR MTB. The genetic mechanisms
      underlying the emergence of MDR MTB strains in this region are poorly understood
      and need to be determined for developing better strategies for TB control. This
      study investigated the frequency of major drug resistance mutations across rpoB,
      katG and inhA loci of Georgian MDR MTB strains and explored differences between
      new and previously treated patients. A total of 634 MTB strains were examined for
      which an MDR phenotype had been previously determined by the proportions method.
      The GenoType(r)MTBDRplus system was applied to screen the strains for the
      presence of rpoB (S531L, H526D, H526Y, and D516V), katG (S315T) and inhA promoter
      region (C15T and T8C) mutations. The target loci were amplified by PCR and then
      hybridized with the respective site-specific and wild type (control) probes.
      RESULTS: Out of the 634 isolates tested considered by phenotypic testing to be
      resistant to RIF and INH, this resistance was confirmed by the
      GenoType(r)MTBDRplus assay in 575 (90.7%) isolates. RIF resistance was seen in
      589 (92.9%) and INH resistance was seen in 584 (92.1%); 67.2% and 84.3% of MDR
      strains harbored respectively rpoB S531L and katG S315T mutations (generally
      known as having low or no fitness cost in MTB). The inhA C15T mutation was
      detected in 22.6% of the strains, whereas rpoB H526D, rpoB H526Y, rpoB D516V and
      inhA T8C were revealed at a markedly lower frequency (<=5.2%). The specific
      mutations responsible for the RIF resistance of 110 isolates (17.4%) could not be
      detected as no corresponding mutant probe was indicated in the assay. There was
      no specific association of the presence of mutations with the gender/age groups.
      All types of prevailing mutations had higher levels in new cases. A great
      majority of the Georgian MDR MTB strains have a strong preference for the drug
      resistance mutations carrying no or low fitness cost. Thus, it can be suggested
      that MDR MTB strains with such mutations will continue to arise in Georgia at a
      high frequency even in the absence of antibiotic pressure.

PMID- 24904759
TI  - Arthroscopic tenoplasty in congenital split biceps long head.
AB  - The long head of the biceps brachii tendon arises mainly from the superior
      glenoid labrum and supraglenoid tubercle. Biceps brachii display anatomic
      variations, but these are rarely encountered. We report, for the first time, a
      technique called arthroscopic intra-articular biceps tenoplasty describing
      restoration of the long head of the biceps tendon using the superior capsule in a
      case of anomalous congenital split biceps tendon encountered incidentally during
      diagnostic glenohumeral arthroscopy in a patient who was treated for shoulder
      instability and SLAP tear. 

PMID- 24904760
TI  - Hip arthroscopy for challenging deformities: global pincer femoroacetabular
      impingement.
AB  - Pincer femoroacetabular impingement occurs in focal or global forms, the latter
      having more generalized and typically more extreme acetabular overcoverage.
      Severe global deformities are often treated with open surgical dislocation of the
      hip. Arthroscopic technical challenges relate to difficulties with hip
      distraction; central-compartment access; and instrument navigation,
      acetabuloplasty, and chondrolabral surgery of the posterior acetabulum.
      Techniques addressing these challenges are introduced permitting dual-portal hip
      arthroscopy with central-compartment access, subtotal acetabuloplasty, and
      circumferential chondrolabral surgery. The modified midanterior portal in
      combination with a zone-specific sequence of acetabular rim reduction monitored
      with fluoroscopic templating enables precision subtotal acetabuloplasty.
      Guidelines for acetabular rim reduction include the following suggested
      radiographic endpoints: postoperative center-edge angle of 35 degrees , a neutral
      posterior wall sign, and an anterior margin ratio of 0.5. Arthroscopic zone
      specific chondrophobic rim preparation and circumferential labral reparative and
      reconstructive techniques and tools permit the arthroscopic treatment of these
      challenging deformities. 

PMID- 24904761
TI  - Arthroscopic glenohumeral arthrodesis with o-arm navigation.
AB  - Glenohumeral arthrodesis is an end-stage salvage operation that has traditionally
      been performed in an open fashion. In recent years an arthroscopic approach has
      been described. The purpose of this report was to present an arthroscopic
      glenohumeral arthrodesis technique with the assistance of O-arm-based navigation.
      An illustrative case example is presented. This technique allows not only a
      minimally invasive glenohumeral arthrodesis but also precise screw fixation by
      navigation, which may be particularly useful in cases of limited bone stock
      and/or bony deformity. 

PMID- 24904762
TI  - Medial patellofemoral ligament reconstruction with a looped semitendinosus
      tendon, using knotless anchor fixation on the patella and hybrid fixation on the
      femur.
AB  - Medial patellofemoral ligament (MPFL) reconstruction is a reliable surgical
      method for stabilizing a dislocating patella, with multiple techniques previously
      described. Although outcomes are generally favorable, the procedure is
      technically demanding and relies on precise identification of native MPFL
      insertion sites, secure fixation of the graft to these sites, and appropriate
      graft tension. We describe a technique for MPFL reconstruction with a looped
      semitendinosus tendon. The 2 free limbs of the graft are secured into blind-end
      patellar sockets with knotless anchors, and the looped end is initially secured
      into a medial femoral socket with a button on the opposite (lateral) cortex. Use
      of an adjustable-loop button allows for gradual adjustment of graft tension, as
      well as re-tensioning after cycling of the knee, before final aperture fixation
      on the femur with an interference screw. 

PMID- 24904764
TI  - Arthroscopic double-locked stitch: a new technique for suturing rotator cuff
      tears.
AB  - There are a number of reasons for failed rotator cuff tear repair. In such cases
      the suture-tendon interface seems to be the most vulnerable area, especially when
      tendon degeneration is present. We describe a new technique, the arthroscopic
      double-locked suture, that increases the tendon fixation and has the added
      benefit of being placed parallel to the blood vessels, therefore avoiding damage
      to the tendon vascularization. The suture may be achieved by use of knots or
      knotless anchors and suture passers, without the need for any additional
      instrumentation. The new technique is especially helpful in cases in which the
      tendon is retracted and degeneration is present, impeding the use of the double
      row technique or its transosseous equivalents. 

PMID- 24904763
TI  - A novel technique for ligamentum teres reconstruction with "all-suture" anchors
      in the medial acetabular wall.
AB  - The function of the ligamentum teres remains poorly understood, but tears have
      been recognized as a source of hip pain. In some patients with complete
      ligamentum teres tears, symptoms of instability are described. Microinstability
      and excess motion are hypothesized to be a source of pain and mechanical
      symptoms. Efforts in recent years to improve symptoms have led to the development
      of techniques used to reconstruct the ligamentum teres, with some early evidence
      that reconstruction can improve symptoms in appropriately selected patients. We
      describe our technique for ligamentum teres allograft reconstruction using
      anchors made only of suture seated in the acetabular floor. 

PMID- 24904765
TI  - Simultaneous medial and lateral patellofemoral ligament reconstruction for
      combined medial and lateral patellar subluxation.
AB  - Medial patellar subluxation (MPS) is a disabling, often iatrogenic patellar
      instability due to previous lateral release for patellar instability. Lateral
      release destabilizes the patella on the lateral side, worsening the initial
      lateral instability and causing MPS. MPS is poorly recognized and may range from
      subluxation to true dislocation. This report describes a technique developed in
      response to episodes of medial and lateral patellar subluxation after failed
      lateral release for patellar instability. The technique uses a graft that extends
      from the medial patellofemoral ligament origin through the quadriceps tendon to
      the lateral epicondyle, thereby reconstructing both the medial and lateral
      patellofemoral ligaments, as well as providing simultaneous stability to both the
      medial and lateral sides of the patella. 

PMID- 24904766
TI  - A novel and cheap method of outside-in meniscal repair for anterior horn tears.
AB  - Outside-in meniscal repair techniques can involve the use of expensive passing
      devices that may not be readily available to all orthopaedic surgeons. There are
      many different ways to repair a meniscus, and we describe a quick and simple
      technique that requires no special equipment. 

PMID- 24904767
TI  - Arthroscopic treatment of calcific tendonitis.
AB  - Calcific tendonitis, or calcifying tendonitis, is a common disorder characterized
      by the multifocal accumulation of basic calcium phosphate crystals within the
      rotator cuff tendons. In most cases, the multifocal calcifications are located 1
      to 2 cm from the insertion of the supraspinatus tendon on the greater tuberosity.
      The initial treatment should be nonoperative including oral anti-inflammatory
      medication and physical therapy. If this is unsuccessful, arthroscopic
      debridement of the deposit is effective. The technique used is an arthroscopic
      localization and debridement without associated subacromial decompression. The
      rotator cuff should be evaluated for partial- and full-thickness tears before and
      after the debridement of calcifications. If a partial- or full-thickness rotator
      cuff tendon tear is identified, it should be treated in a fashion consistent with
      those without associated calcium deposits. In our hands, tears 5 mm or greater in
      depth are repaired using a tendon-to-tendon or tendon-to-bone technique. Tears
      with less depth are debrided and then left alone. Arthroscopic debridement of
      calcific tendonitis can yield excellent functional results and high patient
      satisfaction. 

PMID- 24904768
TI  - Inside out: a novel labral repair and advancement technique.
AB  - Labral tears are a significant cause of hip pain and are currently the most
      common indication for hip arthroscopy. Compared with labral debridement, labral
      repair has significantly better outcomes in terms of both daily activities and
      athletic pursuits in the setting of femoral acetabular impingement. The
      techniques described in the literature all use anchor placement on the capsular
      aspect of the acetabular rim, which can be difficult especially anteriorly, where
      the rim is very thin, and has the potential for significant complications. Anchor
      breakage, anchor slippage into the surrounding (capsular side) soft tissue, and
      penetration of the cartilage surface are among the most common complications. We
      describe an intra-articular anchor placement technique for labral repair from
      inside out. This technique, because of the location of the anchor and direction
      of suture pull, can assist in labral advancement in cases in which the native
      labrum fails to create a seal because of its location away from the femoral head.

PMID- 24904769
TI  - The intracapsular atraumatic arthroscopic technique for closure of the hip
      capsule.
AB  - The hip joint capsule is a critical static stabilizer of the hip. During hip
      arthroscopy, the capsule is breached to gain exposure to treat femoroacetabular
      impingement lesions. There have been recent concerns regarding hip instability
      after hip arthroscopy, and relatively few techniques have been described for
      atraumatic arthroscopic closure of the hip capsule. We describe an atraumatic,
      inside-out, 2-portal technique to repair the capsule. 

PMID- 24904770
TI  - The rigid curette technique for the application of fibrin bioadhesive during hip
      arthroscopy for articular cartilage lesions.
AB  - Encouraging midterm results have recently been reported for the arthroscopic
      treatment of delaminating articular cartilage lesions at the capsulolabral
      junction of the hip joint using fibrin bioadhesive. The needle used to introduce
      the bioadhesive is long, flexible, and often difficult to position. We describe a
      novel technique for introducing the needle that allows accurate placement behind
      the delaminated articular cartilage pocket during hip arthroscopy. 

PMID- 24904771
TI  - T2 Mapping Magnetic Resonance Imaging Encourages an Arthroscopic Approach for
      Osteoid Osteoma in the Acetabulum.
AB  - Intra-articular osteoid osteoma (OO) is uncommon, especially in the hip joint.
      Delayed treatment may cause early osteoarthritis; however, diagnosis and complete
      excision are often challenging. We describe the feasibility of the combination of
      T2 mapping magnetic resonance imaging evaluation and arthroscopic excision of OO
      in the acetabulum. A 12-year-old boy presented with a 6-month history of hip
      pain. An undifferentiated tumor of the medial wall of the acetabulum was
      suspected on radiographs and computed tomography. T2 mapping showed joint
      effusion, and the T2 value of the acetabular cartilage just above the tumor was
      significantly high. These findings suggested OO in the acetabulum. An
      arthroscopic excision was performed for biopsy and excision of the tumor to avoid
      damage to the normal cartilage and growth plate. Histologic examination confirmed
      the OO. At 16 months' follow-up, there was no evidence of recurrence. This is the
      first report to evaluate intra-articular OO by T2 mapping and to treat it
      arthroscopically. Arthroscopic treatment assisted by T2 mapping has excellent
      potential as a minimally invasive technique to enable us to approach the tumor
      from the area of discriminative abnormal cartilage with minimal damage to the
      normal cartilage and surrounding tissue. 

PMID- 24904772
TI  - Ultrasound-assisted hip arthroscopy.
AB  - We describe the use of intraoperative ultrasound for the safe development of
      arthroscopic portals during hip arthroscopy without the requirement for
      fluoroscopy. We find this technique consistently accurate, allowing the safe
      introduction of arthroscopic instruments into the hip with a very low rate of
      iatrogenic injury. We have further developed the technique for application to
      both central- and peripheral-compartment procedures. We now have a total
      experience of more than 700 procedures to date. With the described technique of
      ultrasound guidance for portal placement, fluoroscopy is required in fewer than
      2% of hip arthroscopy procedures at our institution. 

PMID- 24904773
TI  - Arthroscopic reduction of complex dorsal metacarpophalangeal dislocation of index
      finger.
AB  - Complex dorsal dislocation of the metacarpophalangeal joint is an uncommon
      injury, typically caused by entrapment of the volar plate within the joint space.
      Closed reduction of the dislocation is not effective; instead, open reduction is
      necessary to release the soft tissues interposed between the metacarpal head and
      the proximal phalanx. However, an operative risk of digital nerve injury exists
      because of intricate displacement of the normal anatomy. We successfully reduced
      a dislocation by arthroscopic release of the entrapped volar plate. The case
      involved an 11-year-old boy with a complex dorsal dislocation of the
      metacarpophalangeal joint of the right index finger that had failed closed
      reduction. This technique allowed for reliable joint reduction, enabling
      observation of the structures obstructing the reduction; was less invasive; and
      avoided the risk of neurovascular injury. It is a reasonable method to use when
      the volar plate prevents reduction of the dislocation. 

PMID- 24904774
TI  - Anatomic outside-in anterior cruciate ligament reconstruction using a suspension
      device for femoral fixation.
AB  - Cortical suspension is one of the most frequently used methods of femoral
      fixation in anterior cruciate ligament reconstruction. We present a simple
      technique for anterior cruciate ligament reconstruction using a suspension device
      for femoral fixation. The purposes of this technique are to ensure greater
      contact between the graft and the tunnel walls-a goal that is achieved by using
      the femoral fixation device with the shortest possible loop-to avoid the flip
      step and the need for hyperflexion, and in short, to minimize the risk of
      complications that can occur when using the anteromedial portal to drill the
      femoral tunnel. To this end, both the femoral and tibial tunnels are created in
      an outside-in manner and with the same guide. The graft is passed through in a
      craniocaudal direction, and the suspension device is fitted inside an expansion
      piece for a better adaptation to the femoral cortex. 

PMID- 24904775
TI  - Arthroscopic treatment of talar body fractures.
AB  - Talar fractures can be severe injuries with complications leading to functional
      disability. Open reduction-internal fixation remains the treatment of choice for
      displaced talar fractures. Arthroscopic evaluation of the fracture and articular
      surfaces can play an important role in the treatment of these fractures.
      Arthroscopic reduction-internal fixation (ARIF) is increasingly used for certain
      intra-articular fracture types through the body. The minimally invasive nature of
      ARIF and high accuracy are enviable attributes of an evolving technique. This
      technical note describes arthroscopic evaluation of 2 intra-articular talar head
      fractures, using posterior portals, with ARIF performed in 1 case and excision of
      the fracture fragments in the other case. 

PMID- 24904776
TI  - A surgical trick for adjusting an inaccurate guide pin to the center of the
      tibial footprint in anatomic single-bundle anterior cruciate ligament
      reconstruction.
AB  - Anatomic positioning of the graft in anatomic anterior cruciate ligament
      reconstruction is the key to improved knee stability, restoration of normal knee
      kinematics, and the prevention of long-term joint degeneration. We have developed
      a technique for adjusting inaccurate drill guide placement to the center of the
      tibial footprint in anatomic single-bundle anterior cruciate ligament
      reconstruction. This technique can solve the inaccurate drill guide placement
      problems that may be encountered during this surgical procedure. 

PMID- 24904777
TI  - Matrix-associated chondroplasty: a novel platelet-rich plasma and concentrated
      nucleated bone marrow cell-enhanced cartilage restoration technique.
AB  - Bone marrow stimulation techniques such as microfracture for the treatment of
      articular cartilage defects so far solely reproduce mechanically inferior fibrous
      cartilage tissue, which might result in unsatisfactory clinical results at
      midterm. The combination of microfracture and biomaterials-for example,
      autologous matrix-induced chondrogenesis technology-has not yet proved that the
      disadvantages of the marrow stimulation techniques can be overcome. At present,
      only laboratory-cultivated autologous chondrocytes are able to restore a
      biomechanically superior cartilage layer and might lead to superior functional
      results. However, the costs are high and the patient must undergo a 2-stage
      procedure. By selecting the appropriate cell fraction in conjunction with a
      controlled release of differentiating growth factors, sufficient cartilage
      regeneration might be achievable on the basis of bone marrow aspirate as well. We
      thus describe an advanced surgical technique for the treatment of articular
      cartilage defects based on platelet-rich plasma and bone marrow aspirate
      concentrate to overcome these drawbacks. 

PMID- 24904778
TI  - Arthroscopic treatment of bucket-handle labral tear and acetabular fracture.
AB  - Traumatic hip dislocations are associated with chondral and labral pathology as
      well as loose bodies that can be incarcerated in the joint. These types of injury
      often lead to traumatic arthritis. In some cases an osseo-labral fragment may
      become incarcerated in the joint that is not readily visualized preoperatively.
      In place of open surgery, hip arthroscopy permits a technique to remove loose
      bodies and repair labral tears to restore joint congruity and achieve fracture
      reduction and fixation. 

PMID- 24904779
TI  - Hip capsulolabral spacer placement for the treatment of severe capsulolabral
      adhesions after hip arthroscopy.
AB  - Recently, there has been a rapid increase in the number of hip arthroscopies
      performed. The increase in the number of primary surgeries has been associated
      with a similar increase in the number of revision procedures. The most frequent
      indications for revision hip arthroscopy are residual bony deformity
      (impingement), persistent labral pathology, and intra-articular adhesions. Our
      current understanding of capsulolabral adhesions is limited. Although adhesions
      between the capsule and labrum are common after hip arthroscopy, generally, they
      are mild and asymptomatic. However, in severe cases they may cause persistent
      synovitis and pain, and they may tether the labrum away from the femoral head,
      causing loss of the suction-seal effect. Such patients present with nonspecific
      symptoms such as persistent pain, giving way, catching, and pain in hip flexion.
      Magnetic resonance imaging can aid in the diagnosis by showing the absence of
      liquid in the capsulolabral recess, although the definitive diagnosis is based on
      dynamic arthroscopic evaluation. We present our approach to the lysis of
      capsulolabral adhesions with preservation of labral tissue and describe a
      technique that uses an iliotibial band allograft to prevent recurrence of such
      adhesions by maintaining space between the capsule and labrum. 

PMID- 24904780
TI  - Surgical technique for treatment of recalcitrant adductor longus tendinopathy.
AB  - Chronic groin pain in the athlete can be a difficult problem to manage. Adductor
      dysfunction is the most common cause of groin pain in athletes, with the adductor
      longus being the tendon most commonly involved. The most reproducible finding for
      adductor longus tendinopathy is tenderness along the tendon with passive
      abduction and resisted hip adduction in extension. Magnetic resonance imaging and
      injection of a corticosteroid and anesthetic into the proximal muscle-tendon
      junction are both helpful in confirming the diagnosis. Nonoperative treatment may
      consist of protected weight bearing, ice application, ultrasonography, electrical
      stimulation, and gentle stretching with progressive strengthening. However,
      nonoperative management is not always successful. In these instances, surgical
      treatment can be quite effective. We present the indications, surgical technique,
      and rehabilitation protocol of adductor tenotomy for chronic tendinopathy. This
      can prove a useful tool for the treatment of recalcitrant groin pain attributable
      to the adductor longus. 

PMID- 24904781
TI  - Description of the posterolateral rotatory drawer maneuver for the identification
      of posterolateral corner injury.
AB  - Injury to the posterolateral corner (PLC) is difficult to diagnose; most lesions
      of this type are included within the context of complex knee injuries. Study of
      the posterolateral complex is growing in importance because of the complex
      instability generated by these injuries. Although various physical examination
      tests are described for the diagnosis of PLC lesions, in 72% of cases these
      lesions are not identified at their initial presentation, which shows the
      difficulty in both performing these tests and interpreting the results. The
      maneuver described in this report is performed by executing external rotation of
      the leg. With the thumb of the proximally positioned hand, the examiner evaluates
      the positioning of the lateral tibial plateau in relation to the femoral condyle.
      With this maneuver, in lesions of the PLC and particularly lesions of its
      external rotation-restricting structures, we observe external rotation of the
      tibia and posterior subluxation of the lateral tibial plateau that cause the
      anterior edge of the tibial plateau to be posteriorized in relation to the
      anterior edge of the lateral femoral condyle. The idea behind this maneuver is
      not to eliminate the use of other tests but, rather, to add it to a diagnostic
      arsenal that still has interpretation flaws. 

PMID- 24904782
TI  - Anatomic reconstruction of the medial patellofemoral ligament in children and
      adolescents using a pedicled quadriceps tendon graft.
AB  - Reconstruction of the medial patellofemoral ligament (MPFL) has recently become a
      popular procedure for children and adolescents with patellofemoral instability.
      Nevertheless, high complication rates of up to 26% have been reported. The
      traditionally used technique requires patellar bone tunnels that may place the
      proportionately smaller patella at higher risk of fracture. Because of the
      adjacent physis of the femoral insertion, anatomic reconstruction of the MPFL has
      the risk of injury to the growth plate. This technical report therefore presents
      a technique for anatomic reconstruction of the MPFL in a skeletally immature
      population using a pedicled superficial quadriceps tendon graft, hardware-free
      patellar graft attachment, and anatomic femoral fixation distal to the femoral
      physis. The advantages of this technique include avoidance of bony patellar
      complications, an anatomically truer reconstruction, a single incision, and
      sparing of the hamstring tendons for reconstruction of any future ligamentous
      injuries. 

PMID- 24904784
TI  - Using pulsed radiofrequency for chronic pain.

PMID- 24904783
TI  - Defining functional changes in the brain caused by targeted stereotaxic
      radiosurgery.
AB  - Brain tumor patients routinely undergo cranial radiotherapy, and while
      beneficial, this treatment often results in debilitating cognitive dysfunction.
      This serious and unresolved problem has at present, no clinical recourse, and has
      driven our efforts to more clearly define the consequences of different brain
      irradiation paradigms on specific indices of cognitive performance and on the
      underlying cellular mechanisms believed to affect these processes. To accomplish
      this we have developed the capability to deliver highly focused X-ray beams to
      small and precisely defined volumes of the athymic rat brain, thereby providing
      more realistic simulations of clinical irradiation scenarios. Using this
      technique, termed stereotaxic radiosurgery, we evaluated the cognitive
      consequences of irradiation targeted to the hippocampus in one or both
      hemispheres of the brain, and compared that to whole brain irradiation. While
      whole brain irradiation was found to elicit significant deficits in novel place
      recognition and fear conditioning, standard platforms for quantifying hippocampal
      and non-hippocampal decrements, irradiation targeted to both hippocampi was only
      found to elicit deficits in fear conditioning. Cognitive decrements were more
      difficult to demonstrate in animals subjected to unilateral hippocampal ablation.
      Immunohistochemical staining for newly born immature (doublecortin positive) and
      mature (NeuN positive) neurons confirmed our capability to target irradiation to
      the neurogenic regions of the hippocampus. Stereotaxic radiosurgery (SRS) of the
      ipsilateral hemisphere reduced significantly the number of doublecortin and NeuN
      positive neurons by 80% and 27% respectively. Interestingly, neurogenesis on the
      contralateral side was upregulated in response to stereotaxic radiosurgery, where
      the number of doublecortin and NeuN positive neurons increased by 22% and 36%
      respectively. Neuroinflammation measured by immunostaining for activated
      microglia (ED1 positive cells) was significantly higher on the ipsilateral versus
      contralateral sides, as assessed throughout the various subfields of the
      hippocampus. These data suggest that certain cognitive decrements are linked to
      changes in neurogenesis, and that the unilaterally irradiated brain exhibits
      distinct neurogenic responses that may be regulated by regional differences in
      neuroinflammation. Compensatory upregulation of neurogenesis on the contralateral
      hemisphere may suffice to maintain cognition under certain dose limits. Our
      results demonstrate unique cognitive and neurogenic consequences as a result of
      targeted stereotaxic radiosurgery, and suggest that these irradiation paradigms
      elicit responses distinct from those found after exposing the whole brain to more
      uniform radiation fields.

PMID- 24904785
TI  - Effects of premedication with metoprolol on bleeding and induced hypotension in
      nasal surgery.
AB  - BACKGROUND: One of the major problems in surgery is intraoperative bleeding which
      reduces visibility in the operative field. An important task for an anesthetist
      during head and neck surgery is to improve intraoperative visibility. OBJECTIVES:
      The purpose of this study was to compare the amount of bleeding using different
      doses of oral metoprolol during three common types of nasal operation;
      rhinoplasty, septoplasty and functional endoscopic sinus surgery, as this is one
      of the complications during head and neck surgery. PATIENTS AND METHODS: In a
      randomized, controlled, open clinical trial, 88 patients who were candidates for
      nasal operations were studied. Patients entering the study were divided into four
      groups and randomly assigned to receive 50 mg metoprolol a night before the
      operation, 50 mg metoprolol on the day of operation, 50 mg metoprolol on the
      night and on the day of operation, or a placebo. Following the patient's
      preparation on the operating table and after intubation, systolic and diastolic
      blood pressures were measured in a non-invasive oscillometric way, and their
      pulse rate was recorded simultaneously. All the data were recorded during the
      surgery as well. Bleeding was measured by the quality scale proposed by Formme
      and Boezaart. RESULTS: There was a statistical significance between using
      metoprolol and the amount of intraoperative bleeding. All patients who received
      metoprolol the night before surgery and on the day of surgery had slight bleeding
      during the surgery. In addition, there was a statistical significance between
      patients' agitation levels and the time they received metoprolol. CONCLUSIONS:
      Decreases in both systolic blood pressure and heart rate to less than 60 beats
      per minute reduces intraoperative bleeding. These rates can be achieved by using
      beta-blocker drugs. In this study, using a double-dose of metoprolol
      significantly reduced intraoperative bleeding and improved the quality of the
      operative field. It also reduced patients' agitation in the recovery room.

PMID- 24904786
TI  - Whiplash patients with cervicogenic headache after lateral atlanto-axial joint
      pulsed radiofrequency treatment.
AB  - BACKGROUND: Whiplash patients regard cervicogenic headache (CEH) as the most
      burdensome symptom of their condition. Sufferers experience a significant degree
      of disability from headache, associated neck pain and disability, and sleep
      disturbance. Lateral C1/2 joint pulsed radiofrequency (PRF) treatment has been
      shown to produce significant relief from headache in patients with CEH.
      OBJECTIVES: The objective of this retrospective questionnaire study of 45
      consecutive whiplash patients with CEH who had undergone antero-lateral
      atlantoaxial joint pulsed radiofrequency treatment (AA PRF) was to evaluate the
      treatment's long-term effects on pain-related disability and health-related
      quality of life. PATIENTS AND METHODS: Four questionnaires were sent to all 45
      patients who had undergone AA PRF: 1) The short form-36 (SF-36); 2) The neck
      disability index (NDI); 3) The medical outcome scale-sleep scale (MOS-SS); 4) The
      headache impact test-6 (HIT-6). All 45 patients received AA PRF under
      fluoroscopic guidance. PRF treatment was conducted at 45 V with a pulsed
      frequency of 4 Hz and a pulsed width of 10 ms for 4 minutes . RESULTS: Patients
      who responded to the procedure reported lower pain scores at 2, 6, and 12 months
      of follow-up compared to nonresponders. More important, patients reported marked
      improvements in headache impact (P < 0.01), neck-disability scores (P < 0.01),
      awakening due to headache (P < 0.01), and sleep problems (9-item; P < 0.05) on
      the MOS-SS. Responders to the procedure also reported a significantly higher
      health-related quality of life in terms of bodily pain (P < 0.05) and health
      change (P < 0.01) on the SF-36. CONCLUSIONS: In light of the inherent limitations
      of our retrospective study, AA PRF treatment can only be tentatively viewed as a
      promising treatment modality for whiplash patients with CEH and is subject to
      validation in future studies.

PMID- 24904787
TI  - Evaluation of pulsed radiofrequency denervation in the treatment of chronic
      facetjoint pain: an observational study.
AB  - BACKGROUND: Low back disorder is the most common problem in the entire spinal
      axis. About two-thirds of adults suffer from low back pain (LBP) at some time.
      Pain generators in the lumbar spine include the annulus of the disc, the
      posterior longitudinal ligament, a portion of the dural membrane, the facet
      joints, the spinal nerve roots and ganglia, and the associated paravertebral
      muscle fascia. There is no doubt that the facet joint is a potential source of
      chronic LBP. Facet joints are true synovial joints that have a joint space,
      hyaline cartilage surfaces, a synovial membrane, and a fibrous capsule. Two
      medial branches of the dorsal rami innervate the facet joints. If conservative
      measures fail in the treatment of facet joint pain, pulsed radiofrequency (PRF)
      of the medial branches can be administered. OBJECTIVES: The aim of this
      observational study was to evaluate the efficacy of PRF in the treatment of
      lumbar chronic facet joint pain. PATIENTS AND METHODS: In this prospective
      observational study, we selected 300 patients who suffered from lumbar facet
      joint pain, were referred to the Pain Therapy Department, and underwent PRF
      treatment of the lumbar medial branches. We analyzed patients with facet joint
      pain that was unresponsive to conventional treatment, with a positive response to
      diagnostic medial branch block, who underwent PRF of the lumbar area for 18
      months at San Giovanni Hospital of Rome. RESULTS: Three hundred patients were
      eligible for the study. After 1 month, 62% of patients (186 patients) reported
      good pain relief [95% confidence interval (CI) 0.53, 0.7]; 8.6% (26 patients)
      reported excellent pain relief (95% CI 0.07-0.09); 20. 4% (61 patients) reported
      poor pain relief (95% CI 0.18-0.22), and 9% (27 patients) reported no pain relief
      (95% CI 0.08-0.099). The average pain numeric rating scale (NRS) score before the
      procedure was 6 (range 4-9), decreasing to 2 after the procedure (range 0-4). SF
      36 physical and mental parameters improved significantly after the treatment [>=
      1 standard deviation (SD)]. Results after 6 months were similar to those obtained
      after 1 month. CONCLUSIONS: This study suggests that PRF treatment of the lumbar
      medial branches provides good pain relief for at least 6 months in 70% of
      patients who suffer from lumbar facet joint pain.

PMID- 24904788
TI  - Caudal additives do not improve the analgesia afforded by levobupivacaine after
      hypospadias repair.
AB  - BACKGROUND: Caudal analgesia is commonly employed to provide excellent intra- and
      postoperative analgesia for primary hypospadias repair in children. Several
      additives to local anesthetics are commonly employed to increase the block
      duration, although these have uncertain benefits. OBJECTIVES: This study
      investigated whether, in caudal analgesia with levobupivacaine 0.25%, the
      addition of S (+)-ketamine, clonidine, or both agents combined, would prolong
      postoperative analgesia in patients undergoing primary hypospadias repair.
      PATIENTS AND METHODS: We conducted a retrospective chart analysis for all
      patients who underwent hypospadias repair with caudal analgesia over a
      consecutive 3-period at this institution. The study examined four patient groups,
      classified according to the analgesia used: No additive, levobupivacaine
      aloneLevobupivacaine and S (+)-ketamineLevobupivacaine and
      clonidineLevobupivacaine, S (+)-ketamine, and clonidinePRIMARY OUTCOME MEASURES
      WERE AS FOLLOWS: time to the first postoperative request for analgesia, total
      first 24-hour postoperative analgesia, and time to hospital discharge. RESULTS:
      The 87 patients included had a mean +/- SD age of 21.4 +/- 13.5 months and weight
      of 11.9 +/- 2.4 kg. The median doses of levobupivacaine, S (+)-ketamine, and
      clonidine were 0.7 mg/kg (range, 0.4-1.3), 0.5 mg/kg (0.2-1.1), and 1.8 MUg/kg
      (0.8-2.3), respectively. The addition of S(+)-ketamine, clonidine, or both did
      not increase the time to first oral analgesia request. Neither did it reduce the
      total first 24-hour postoperative analgesia requirements or alter hospital
      discharge time. However, the additive drugs in combination did increase
      postoperative sedation. CONCLUSIONS: The addition of S (+)-ketamine or clonidine
      to levobupivacaine 0.25% in caudal analgesia for hypospadias repair appears to be
      of no benefit. However, use of the additives in combination increased
      postoperative sedation.

PMID- 24904789
TI  - Comparative evaluation of continuous lumbar paravertebral versus continuous
      epidural block for post-operative pain relief in hip surgeries.
AB  - BACKGROUND: Effective control of postoperative pain remains one of the most
      important and pressing issues in the field of surgery and has a significant
      impact on our health care system. In too many patients, pain is treated
      inadequately, causing them needless suffering and they can develop complications
      as an indirect consequence of pain. Analgesic modalities, if properly applied,
      can prevent or at least minimize this needless suffering and these complications.
      OBJECTIVES: The aim of this study was to compare the efficacy of continuous
      infusions of local anesthetic drugs by paravertebral and epidural routes in
      controlling postoperative pain in patients undergoing hip surgeries. PATIENTS AND
      METHODS: The study involved 60 patients who were undergoing hip surgery under the
      subarachnoid block. They were randomly divided into 2 groups of 30 patients.
      Group I (paravertebral group) received a single dose of spinal anesthesia with
      2.5 mL 0.5% bupivacaine (heavy) + a continuous infusion of 0.125% bupivacaine at
      5 mL/h in the paravertebral space. Group II (epidural group) received a single
      dose of spinal anesthesia with 0.5% bupivacaine (heavy) + a continuous infusion
      of 0.125% bupivacaine at a rate of 5 mL/hr in the epidural space for 48 hours in
      the postoperative period. Visual analogue scale (VAS) score, vital statistics,
      rescue analgesia, and procedure time were compared with the corresponding times
      between the 2 groups by student's t-test and repeated measures ANOVA with post
      hoc Bonferroni. P < 0.05 was considered significant. There were no statistically
      significant differences between the 2 groups regarding mean pain score in the
      first 48 hours. RESULTS: Mean arterial pressure was significantly lower in the
      epidural group compared with the paravertebral group from 2 hours after start of
      the infusion until 48 hrs. Regional anesthesia procedure time was significantly
      longer in the epidural group (P < 0.001). There was no significant difference
      between the 2 groups regarding frequency of postoperative complications and
      catheter-related problems. CONCLUSIONS: The results of our study indicate that
      for patients who are scheduled for hip surgery, both continuous paravertebral and
      continuous epidural analgesia are effective in controlling postoperative pain but
      that the former has several crucial advantages.

PMID- 24904790
TI  - Pain management after surgery: a brief review.
AB  - Proper pain management, particularly postoperative pain management, is a major
      concern for clinicians as well as for patients undergoing surgery. Although many
      advances have been made in the field of pain management, particularly during the
      past decades, not all patients achieve complete relief from postoperative pain.
      In this paper, we have emphasized the importance of postoperative analgesia and
      discussed the new developments in this field. 

PMID- 24904791
TI  - Scalp block for awake craniotomy in a patient with a frontal bone mass: a case
      report.
AB  - "Anesthesia" for awake craniotomy is a unique clinical condition that requires
      the anesthesiologist to provide changing states of sedation and analgesia, to
      ensure optimal patient comfort without interfering with electrophysiologic
      monitoring and patient cooperation, and also to manipulate cerebral and systemic
      hemodynamics while guaranteeing adequate ventilation and patency of airways.
      Awake craniotomy is not as popular in developing countries as in European
      countries. This might be due to the lack of information regarding awake
      craniotomy and its benefits among the neurosurgeons and anesthetists in
      developing countries. From the economic perspective, this procedure may decrease
      resource utilization by reducing the use of invasive monitoring, the duration of
      the operation, and the length of postoperative hospital stay. All these reasons
      also favor its use in the developing world, where the availability of resources
      still remains a challenge. In this case report we presented a successful awake
      craniotomy in patient with a frontal bone mass. 

PMID- 24904792
TI  - Pain of chronic sacro-iliac joint atrhopathy: managed successfully with
      conventional bipolar radiofrequency procedure: a case report.
AB  - BACKGROUND: Chronic sacroiliac (SI) joint pain constitutes 16% to 30% of the
      total prevalence of chronic low back pain, which is commonly unilateral. Apart
      from conservative management, various interventional pain management procedures
      have been reported. Intraarticular deposteroid injection has been described as
      the most evidence-based, but different various radio frequency (RF) procedures
      have been described with varied success. Conventional bipolar RF is relatively
      new in the management of SI joint pain. We have successfully managed pain of the
      SI joint origin. CASE REPORT: A 53-year-old female who presented with unilateral
      back pain with radiation to the leg was diagnosed with pain from SI joint
      arthropathy by clinical and diagnostic interventional procedures. She was treated
      conservatively without any result. Deposteriod gave good but very short-term
      relief. She underwent a bipolar RF procedure. An RF needle was placed at the L5
      medial branch, and 2 were placed on each lateral side of the sacral foramina for
      the lateral branches of the S1, S2, and S3 nerve roots. Conventional RF was
      performed at 80 degrees C for 90 seconds. DISCUSSION: This case report supports
      the use of bipolar RF nerve ablation for chronic sacroiliac joint pain that does
      abate with deposteroid injection. In this patient, the Rt L5 medial branch nerve
      was ablated using conventional RF technique, followed by conventional bipolar RF
      nerve ablation for the S1, S2 and S3 lateral branches. We recommend the use of
      bipolar RF nerve ablation for chronic sacroiliac joint pain that has an
      inadequate response to deposteroid injection.

PMID- 24904794
TI  - Post-dural puncture headache: haunts the anaesthetist.

PMID- 24904793
TI  - Pulsed radiofrequency of lumbar dorsal root ganglion for chronic postamputation
      phantom pain.
AB  - Chronic pain following lower-limb amputation is now a well-known neuropathic,
      chronic-pain syndrome that usually presents as a combination of phantom and stump
      pain. Controlling these types of neuropathic pain is always complicated and
      challenging. If pharmacotherapy does not control the patient's pain,
      interventional procedures have to be taken. The aim of this study was to evaluate
      the efficacy of using pulsed radiofrequency (PRF) on the dorsal root ganglia at
      the L4 and L5 nerve roots to improve phantom pain. Two patients with phantom pain
      were selected for the study. After a positive response to segmental nerve
      blockade at the L4 and L5 nerve roots, PRF was performed on the L4 and L5 dorsal
      root ganglia. Global clinical improvement was good in one patient, with a 40%
      decrease in pain on the visual analogue scale (VAS) in 6 months, and moderate in
      the second patient, with a 30% decrease in pain scores in 4 months. PRF of the
      dorsal root ganglia at the L4 and L5 nerve roots may be an effective therapeutic
      option for patients with refractory phantom pain. 

PMID- 24904795
TI  - Commentary on: Quality-of-Life Evaluation of Patients Undergoing Lumbar
      Discectomy Using Short Form 36.

PMID- 24904796
TI  - Trigeminal neuralgia: a condition to be better understood.

PMID- 24904797
TI  - Quality of life evaluation.

PMID- 24904798
TI  - Importance of choice of drugs and timing of their administration.

PMID- 24904799
TI  - Why don't all individuals who undergo dura mater/arachnoid puncture develop
      postdural puncture headache?

PMID- 24904800
TI  - Tracheal intubation without use of muscle relaxants: comparison of remifentanil
      and alfentanil.

PMID- 24904801
TI  - The anatomical distribution of trigeminal neuralgia: a perspective and future
      directions.

PMID- 24904803
TI  - Would we be able to vaildate diagnostic criteria and pave the way for discerning
      causality in trigeminal neuralgia?

PMID- 24904802
TI  - Commentary on: Trigeminal Neuralgia: Frequency of Occurrence in Different Nerve
      Branches.

PMID- 24904804
TI  - Are we anesthesiologists, aware about the incidence of muscle stiffness
      associated with remifentanil?

PMID- 24904805
TI  - Interventional pain management according to evidence-based medicine.

PMID- 24904806
TI  - Pain management in the intensive care unit: do we need special protocols?

PMID- 24904808
TI  - Effects of suppository acetaminophen, bupivacaine wound infiltration, and caudal
      block with bupivacaine on postoperative pain in pediatric inguinal herniorrhaphy.
AB  - BACKGROUND: The control of postoperative pain is important in children, and poor
      pain control leads to organ dysfunction and behavioral problems. OBJECTIVES: We
      compared the analgesic effects of suppository acetaminophen, bupivacaine wound
      infiltration, and caudal block with bupivacaine on postoperative pain in
      pediatric inguinal herniorrhaphy. PATIENTS AND METHODS: In this double-blinded,
      randomized controlled clinical trial, 90 children of American Society of
      Anesthesiologists (ASA) grade I-II, aged between 3 months and 7 years, and
      scheduled for elective unilateral inguinal herniorrhaphy under general anesthesia
      were assigned to three equal groups. Patients in the first group received 20
      mg/kg of suppository acetaminophen. In the second group, 2 mg/kg of 0.5%
      bupivacaine was infiltrated in the incisional site, and in the third group, a
      caudal block was performed with 0.75 mL/kg of 0.25% bupivacaine. The Face, Legs,
      Activity, Cry, Consolability (FLACC) pain scale was applied 30 minutes after
      operation. Thereafter, the FLACC score was obtained every hour during the next 6
      hours. If the FLACC score was 4 or over, we administered 0.5 mg/kg of intravenous
      meperidine. The data was transferred to SPSS-10 software and analyzed
      statistically with chi-square and analysis of variance tests. P < 0.05 was
      considered significant. RESULTS: The mean analgesic duration in the
      acetaminophen, bupivacaine infiltration, and caudal block groups was 4.07, 5.40,
      and 5.37 hours, respectively. Significant differences were not observed between
      the bupivacaine infiltration and caudal block groups (P = 0.9), but the
      differences between the bupivacaine infiltration and acetaminophen groups (P =
      0.034) and the caudal block and acetaminophen groups (P = 0.039) were
      significant. With regard to meperidine administration, significant differences
      were not observed between the bupivacaine infiltration and caudal block groups (P
      = 0.848), but significant differences were observed between these two groups and
      the acetaminophen group (P < 0.05). CONCLUSIONS: Patients in the bupivacaine
      infiltration and caudal block groups had less postoperative pain than those in
      the acetaminophen group and received lower amount of meperidine. We concluded
      that in children, bupivacaine infiltration and caudal block with bupivacaine
      produce better analgesia than suppository acetaminophen. It seems that
      bupivacaine infiltration is better than caudal block because of its simplicity,
      lower incidence of complications, and failure rate.

PMID- 24904807
TI  - Postoperative pain control for total knee arthroplasty: continuous femoral nerve
      block versus intravenous patient controlled analgesia.
AB  - BACKGROUND: Pain after total knee arthroplasty is severe and impacts functional
      recovery. OBJECTIVES: We performed a retrospective study, comparing conventional
      patient control analgesia (PCA) modalities versus continuous femoral nerve
      blockade (CFNB) for 1582 post-TKA (total knee arthroplasty) patients. PATIENTS
      AND METHODS: Using our electronic acute pain service (APS) database, we reviewed
      the data of 579 patients who had received CFNBs compared with 1003 patients with
      intravenous PCA over 4 years. RESULTS: Our results show that the incidence of a
      severe pain episode was higher in the PCA compared with the CFNB group. Lower
      pain scores were observed in the CFNB group compared with the PCA group from
      postoperative day (POD) 1 to 3, primarily due to lower rest pain scores in the
      CFNB group. CONCLUSIONS: Our study shows that there is improvement in pain
      scores, at rest and on movement, as well as a reduction in incidence of severe
      pain, in patients who receive CFNB versus those who receive intravenous PCA.

PMID- 24904809
TI  - Premedication with midazolam nasal spray: an alternative to oral midazolam in
      children.
AB  - BACKGROUND: Midazolam is a water soluble benzodiazepine which is frequently
      administered by intravenous and oral routes in our institution. Its nasal spray
      has become recently available. OBJECTIVES: To compare the efficacy of midazolam
      administered orally and by intranasal spray, with the specific objective of
      assessing their efficacy in terms of acceptability to the patients, whether they
      achieve a satisfactory sedation score, and the overall ease of inducing general
      anesthesia. PATIENTS AND METHODS: Sixty healthy children of ASA grade I or II,
      aged 2-6 years who were undergoing elective surgery of approximately 30 minutes
      duration, were assigned to receive midazolam premedication in a randomized
      controlled trial. They were divided into 2 groups of 30 patients each. Group I:
      30 patients received midazolam orally (parenteral solution mixed in honey). Group
      II: 30 patients received a commercially available midazolam nasal spray. RESULTS:
      The study shows that children better accepted the drug when administered orally
      than when administered intranasally, although satisfactory sedation scores at 10
      and 20 minutes were better in the nasal spray group than in the oral group [i.e.,
      6 (20%) vs. 0 (0%) at 10 min and 16 (53.3%) vs. 13 (43.3%), respectively].
      Satisfactory ease of induction scores [24 (80%) vs. 13 (43.3%)], recovery times
      [11.63 +/- 4.19 minutes vs. 25.20 +/- 9.36 minutes], and post-anesthesia recovery
      scores were better in the nasal spray group (group II) than in the oral group
      (group I). CONCLUSIONS: On the basis of our study, we conclude that nasal
      midazolam spray is acceptable and is a good alternative to oral midazolam as
      premedication in the pediatric population.

PMID- 24904810
TI  - Effect of clonidine premedication on blood loss in spine surgery.
AB  - BACKGROUND: Blood loss in spine surgery is an important issue, even though it has
      been understudied compared with hip and knee arthroplasty. OBJECTIVES: In this
      study, we evaluated the effect of oral clonidine as premedication on blood loss
      in lumbar spine fusion surgery under anesthesia with propofol and remifentanil.
      PATIENTS AND METHODS: In this double-blind, randomized clinical trial, 30
      patients who were undergoing lumbar spine posterior fusion surgery due to
      traumatic fracture were allocated randomly into 2 groups. The study group
      (clonidine group) received a 200-MUg oral clonidine tablet 60-90 minutes before
      anesthesia, and the control group received placebo at the same time. Induction
      and maintenance of anesthesia and the mean target arterial pressure for
      controlled hypotension with remifentanil were the same in the 2 groups. We
      compared the amount of intraoperative blood loss, dose of remifentanil/hour
      administered, need for nitroglycerine to reach the mean target arterial pressure
      when remifentanil was insufficient, duration of operation, and surgeon's
      satisfaction of a bloodless field between groups. RESULTS: There was no
      statistically significant difference between groups in age (P = 0.115), sex (P =
      0.439), weight (P = 0.899), operation time (P = 0.2), or American Society of
      Anesthesiologists physical status score (P = 0.390). Intraoperative blood loss
      and remifentanil dose administered per hour in the clonidine group were
      significantly less than in the control group (P = 0.002 and P = 0.001,
      respectively), but there was no significant difference in surgeon's satisfaction
      between groups (P = 0.169). CONCLUSIONS: As an oral premedication, clonidine can
      reduce surgical blood loss in lumbar spine posterior fusion surgery, even at the
      same levels of mean arterial pressure (MAP) with the control group. Its use can
      be studied in more complicated spine surgeries, such as scoliosis and spinal
      deformity surgeries.

PMID- 24904811
TI  - Pulsed radiofrequency treatment for trigeminal neuralgia.
AB  - BACKGROUND: Pulsed radiofrequency (PRF) treatment is defined as the delivery of
      short pulses of radiofrequency via a needle tip, which does not result in an
      actual thermal lesions. There are mixed views regarding the use of PRF for
      trigeminal neuralgia (TN). In our opinion, one of the main reasons for the
      contrasting views is the insufficient PRF dose employed in previous studies. In a
      recent study on the effects of PRF on resiniferatoxin-induced neuropathic pain in
      an animal model, the anti-allodynic effects of PRF were significantly greater
      when the PRF exposure duration was increased from 2 to 6 minutes. OBJECTIVES: The
      primary objective of this retrospective study is to report the results for 36
      consecutive patients who underwent PRF treatment for TN, for 6 minutes at 45 V at
      a pulsed frequency of 4 Hz and a pulse width of 10 ms. PATIENTS AND METHODS: For
      the study, we obtained procedural records of 36 consecutive patients. Their
      current state of pain was evaluated over a telephonic survey and the post
      procedural data at 2, 6, and 12 months were retrieved thereafter from the patient
      records. The main outcome measure was excellent pain relief (more than 80%),
      which was assessed at 2, 6, and 12 months. RESULTS: The percentages of patients
      who showed excellent pain relief (> 80% pain relief) at 2, 6, and 12 months were
      73.5% (25/34), 61.8% (21/34), and 55.9% (19/34), respectively. The percentages of
      patients showing satisfactory pain relief (50-80% pain relief) at 2, 6, and 12
      months were 14.7% (5/34), 17.6% (6/34), and 17.6% (6/34), respectively, and those
      of patients showing less than satisfactory pain relief (< 50% pain relief) at 2,
      6, and 12 months were 11.8% (4/34), 20.6% (7/34), and 23.5% (8/34), respectively.
      No complications were reported, and none of the patients required
      hospitalization. CONCLUSIONS: PRF of the trigeminal ganglion should be further
      evaluated as an alternative treatment method for TN.

PMID- 24904812
TI  - Use of oxycodone in pain management.
AB  - Oxycodone is widely used to alleviate moderate-to severe acute pain, It is an
      effective analgesic for many types of pain, and is especially useful for
      paroxysmal spontaneous pain, steady pain, allodynia associated with postherpetic
      neuralgia, and it is also increasingly used in the management of cancer-related
      and chronic pain, oxycodone has been found to improve the quality of life of
      patients with many types of pain. In 2011, following chemical and physical
      manipulation, an extended-release form of oxycodone was developed in order to
      maintain its rate-controlling mechanism. This new formulation significantly
      improved analgesia among patients with moderate-to-severe chronic osteoarthritis
      pain with an adverse event profile similar to that of other opioids. The long
      term safety and efficacy of extended-release form of oxycodone in relieving
      moderate-to-severe chronic pain has been demonstrated. In this study we discussed
      about different aspects of this drug in managing of various types of pain. 

PMID- 24904813
TI  - Commentary on: Use of Remifentanil and Alfentanil in Endotracheal Intubation: A
      Comparative Study.

PMID- 24904814
TI  - Endotracheal intubation without neuromuscular blocking agents: is it a good and
      safe option?

PMID- 24904815
TI  - Commentary on: Quality of Life Evaluation of Patients Undergoing Lumbar
      Discectomy Using Short Form 36.

PMID- 24904816
TI  - Trigeminal pain and its distribution in different trigeminal nerve branches.

PMID- 24904817
TI  - Post-dural puncture headache.

PMID- 24904818
TI  - Assessing quality of life in spinal surgery.

PMID- 24904819
TI  - Remifentanil or alfentanil for endotracheal intubation.

PMID- 24904822
TI  - Companion diagnostics for targeted cancer drugs - clinical and regulatory
      aspects.
AB  - Companion diagnostics (CDx) holds the promise of improving the predictability of
      the oncology drug development process and become an important tool for the
      oncologist in relation to the choice of treatment for the individual patient. A
      number of drug-diagnostic co-development programs have already been completed
      successfully, and in the clinic, the use of several targeted cancer drugs is now
      guided by a CDx. This central role of the CDx assays has attracted the attention
      of the regulators, and especially the US Food and Drug Administration has been at
      the forefront in relation to developing regulatory strategies for CDx and the
      drug-diagnostic co-development project. For an increasing number of cancer
      patients the treatment selection will depend on the result generated by a CDx
      assay, and consequently this type of assay has become critical for the care and
      safety of the patients. In order to secure that the CDx assays have a high degree
      of analytical and clinical validity, they must undergo an extensive non-clinical
      and clinical testing before release for routine patient management. This review
      will give a brief introduction to some of the scientific and medical challenges
      related to the CDx development with specific emphasis on the regulatory
      requirements in different regions of the world. 

PMID- 24904821
TI  - Role of integrin alpha4 in drug resistance of leukemia.
AB  - Chemotherapeutic drug resistance in acute lymphoblastic leukemia (ALL) is a
      significant problem, resulting in poor responsiveness to first-line treatment or
      relapse after transient remission. Classical anti-leukemic drugs are non-specific
      cell cycle poisons; some more modern drugs target oncogenic pathways in leukemia
      cells, although in ALL these do not play a very significant role. By contrast,
      the molecular interactions between microenvironment and leukemia cells are often
      neglected in the design of novel therapies against drug resistant leukemia. It
      was shown however, that chemotherapy resistance is promoted in part through cell
      cell contact of leukemia cells with bone marrow (BM) stromal cells, also called
      cell adhesion-mediated drug resistance (CAM-DR). Incomplete response to
      chemotherapy results in persistence of resistant clones with or without
      detectable minimal residual disease (MRD). Approaches for how to address CAM-DR
      and MRD remain elusive. Specifically, studies using anti-functional antibodies
      and genetic models have identified integrin alpha4 as a critical molecule
      regulating BM homing and active retention of normal and leukemic cells. Pre
      clinical evidence has been provided that interference with alpha4-mediated
      adhesion of ALL cells can sensitize them to chemotherapy and thus facilitate
      eradication of ALL cells in an MRD setting. To this end, Andreeff and colleagues
      recently provided evidence of stroma-induced and alpha4-mediated nuclear factor
      kappaB signaling in leukemia cells, disruption of which depletes leukemia cells
      of strong survival signals. We here review the available evidence supporting the
      targeting of alpha4 as a novel strategy for treatment of drug resistant leukemia.

PMID- 24904823
TI  - Targeting T cell immunometabolism for cancer immunotherapy; understanding the
      impact of the tumor microenvironment.
AB  - The immune system has a key role to play in controlling cancer initiation and
      progression. T cell activation, which is central to anti-tumor immune responses,
      coincides with changes in cellular metabolism. Naive T cells predominantly
      require an ATP generating metabolic profile, whereas proliferating effector T
      cells require anabolic metabolic profiles that promote rapid growth and
      proliferation. Furthermore, specific T cell subsets require distinct energetic
      and biosynthetic pathways to match their functional requirements. The often
      hostile tumor microenvironment can affect T cell immune responses by altering the
      resulting cellular metabolism. Tailoring immune responses by manipulating
      cellular metabolic pathways may provide an exciting new option for cancer
      immunotherapy. T cell responses might also be skewed via metabolic manipulation
      to treat the complications of obesity-associated inflammation, which is a rapidly
      growing global health problem and a major risk factor for many malignancies. In
      this review, the diverse metabolic requirements of T cells in anti-tumor immunity
      are discussed, as well as the profound influence of the tumor microenvironment
      and the possible avenues for manipulation to enhance anti-tumor immunity. 

PMID- 24904824
TI  - Targeting the PI3K/mTOR Pathway in Pediatric Hematologic Malignancies.
AB  - A complex interplay of intracellular signaling networks orchestrates normal cell
      growth and survival, including translation, transcription, proliferation, and
      cell cycle progression. Dysregulation of such signals occurs commonly in many
      malignancies, thereby giving the cancer cell a survival advantage, but also
      providing possible targets for therapeutic intervention. Activation of the
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of
      rapamycin (mTOR) signaling pathway contributes to the proliferative advantage of
      malignant cells and may confer resistance to chemotherapy in various hematologic
      malignancies. The initial mTOR inhibitor, sirolimus (also known as rapamycin),
      was first discovered in 1975 in the soil of Easter Island. Sirolimus was
      originally developed as an anti-fungal agent given its macrolide properties, but
      was approved by the Food and Drug Administration (FDA) in 1999 as an
      immunosuppressive agent for renal transplantation patients once its T cell
      suppression characteristics were recognized. Shortly thereafter, recognition of
      sirolimus's ability to inhibit cellular proliferation and cell cycle progression
      brought sirolimus to the forefront as a possible inhibitor of mTOR. In the
      subsequent decade, the functional roles of the mTOR protein have been more fully
      elucidated, and this protein is now known to be a key regulator in a highly
      complex signaling pathway that controls cell growth, proliferation, metabolism,
      and apoptosis. This article discusses the dysregulation of PI3K/mTOR signaling in
      hematologic malignancies, including acute and chronic leukemias, lymphomas, and
      lymphoproliferative disorders. The current repertoire of PI3K/mTOR pathway
      inhibitors in development and clinical trials to date are described with emphasis
      upon pediatric hematologic malignancies (Figure 1). Investigation of small
      molecule inhibitors of this complex signaling network is an active area of
      oncology drug development. 

PMID- 24904825
TI  - Clinical Benefit from Ipilimumab Therapy in Melanoma Patients may be Associated
      with Serum CTLA4 Levels.
AB  - Stage IV metastatic melanoma patients historically have a poor prognosis with 5
      10% 5-year survival. Ipilimumab, a monoclonal antibody against cytotoxic T
      lymphocyte antigen 4 (CTLA4), is one of the first treatments to provide
      beneficial durable responses in advanced melanoma. However, less than 25% of
      those treated benefit, treatment is expensive, and side effects can be fatal.
      Since soluble (s) CTLA4 may mediate inhibitory effects previously ascribed to the
      membrane-bound isoform (mCTLA4), we hypothesized patients benefiting from
      ipilimumab have higher serum levels of sCTLA4. We found that higher sCTLA4 levels
      correlated both with response and improved survival in patients treated with
      ipilimumab in a small patient cohort [patients with (n = 9) and without (n = 5)
      clinical benefit]. sCTLA4 levels were statistically higher in ipilimumab-treated
      patients with response to ipilimumab. In contrast, sCTLA4 levels did not
      correlate with survival in patients who did not receive ipilimumab (n = 11).
      These preliminary observations provide a previously unrecognized link between
      serum sCTLA4 levels and response to ipilimumab as well as to improved survival in
      ipilimumab-treated melanoma patients and a potential mechanism by which
      ipilimumab functions. 

PMID- 24904820
TI  - The CK1 Family: Contribution to Cellular Stress Response and Its Role in
      Carcinogenesis.
AB  - Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family
      play major regulatory roles in many cellular processes including DNA-processing
      and repair, proliferation, cytoskeleton dynamics, vesicular trafficking,
      apoptosis, and cell differentiation. As a consequence of cellular stress
      conditions, interaction of CK1 with the mitotic spindle is manifold increased
      pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is
      able to alter the activity of key proteins in signal transduction and signal
      integration molecules. In line with this notion, CK1 is tightly connected to the
      regulation and degradation of beta-catenin, p53, and MDM2. Considering the
      importance of CK1 for accurate cell division and regulation of tumor suppressor
      functions, it is not surprising that mutations and alterations in the expression
      and/or activity of CK1 isoforms are often detected in various tumor entities
      including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer,
      adenocarcinomas of the pancreas, and ovarian cancer. Therefore, scientific effort
      has enormously increased (i) to understand the regulation of CK1 and its
      involvement in tumorigenesis- and tumor progression-related signal transduction
      pathways and (ii) to develop CK1-specific inhibitors for the use in personalized
      therapy concepts. In this review, we summarize the current knowledge regarding
      CK1 regulation, function, and interaction with cellular proteins playing central
      roles in cellular stress-responses and carcinogenesis. 

PMID- 24904826
TI  - The therapeutic potential of class I selective histone deacetylase inhibitors in
      ovarian cancer.
AB  - Epithelial ovarian cancer remains the deadliest gynecologic malignancy. Despite
      advances in treatment, new approaches are needed. Histone deacetylases (HDACs)
      are a family of enzymes that regulate gene expression by removing acetyl groups
      from lysine residues on histones and non-histone proteins. Inhibition of HDACs
      with small molecules has led to the development of histone deacetylase inhibitors
      (HDACi) that are in clinical use, primarily for hematologic malignancies.
      Although clinical trials with HDACi as single agents in solid tumors have been
      disappointing, data from independent labs and recent work by our group show that
      class I selective HDACi have potent anti-tumor effects in pre-clinical models of
      ovarian cancer. This review summarizes the role of HDACs in ovarian cancer and
      the potential niche for selective class I HDACi, particularly HDAC3 in ovarian
      cancer therapy. 

PMID- 24904827
TI  - MicroRNA Machinery Genes as Novel Biomarkers for Cancer.
AB  - MicroRNAs (miRNAs) directly and indirectly affect tumorigenesis. To be able to
      perform their myriad roles, miRNA machinery genes, such as Drosha, DGCR8, Dicer1,
      XPO5, TRBP, and AGO2, must generate precise miRNAs. These genes have specific
      expression patterns, protein-binding partners, and biochemical capabilities in
      different cancers. Our preliminary analysis of data from The Cancer Genome Atlas
      consortium on multiple types of cancer revealed significant alterations in these
      miRNA machinery genes. Here, we review their biological structures and functions
      with an eye toward understanding how they could serve as cancer biomarkers. 

PMID- 24904830
TI  - Adenocarcinoma arising from sacrococcygeal mature teratoma in an adult female:
      report of a case.
AB  - We report a case of adenocarcinoma arising from a sacrococcygeal mature teratoma
      in an adult female. A 62-year-old female was diagnosed with a presacral tumor 10
      years ago. Pelvic computed tomography (CT) demonstrated a presacral heterogeneous
      tumor, containing multiloculated cystic area and enhanced solid component with
      calcification. Percutaneous needle biopsy for the solid component of the tumor
      identified an adenocarcinoma and the patient was diagnosed as having a
      sacrococcygeal teratoma with malignant transformation. Abdomino-sacral rectal
      resection with sacral amputation at the upper edge of the S5 was performed. The
      pathological diagnosis was adenocarcinoma derived from a mature teratoma. The
      tumor cells had infiltrated the rectal wall. After 7 months, a follow-up CT
      demonstrated swelling of the right inguinal lymph nodes and a right inguinal
      lymphadenectomy was performed. Pathological examination showed metastatic lymph
      nodes. The patient is doing well 21 months after the second surgery, with no
      signs of recurrence. 

PMID- 24904829
TI  - Dihydroartemisinin is a Hypoxia-Active Anti-Cancer Drug in Colorectal Carcinoma
      Cells.
AB  - Tumor hypoxia is one main biological factor that drives resistance to
      chemotherapy and radiotherapy. To develop a novel strategy for overcoming hypoxia
      induced therapy resistance, we examined the anti-neoplastic activity of the
      reactive oxygen donor dihydroartemisinin (DHA) in human colon cancer cell lines
      in normoxia and severe hypoxia. In addition, we analyzed the involvement of the
      intrinsic apoptosis pathway for DHA-mediated cytotoxicity in HCT116 cells in
      short-term and long-term in vitro assays. When applied at lower concentrations
      (<=25 MUM), DHA induced apoptosis in Colo205, HCT15, and HCT116 cells, whereas
      necrotic cell death was increased when cells were treated with higher DHA
      concentrations (50 MUM). However, no preference for DHA-induced apoptosis or
      necrosis could be detected between the treatment under normoxic or hypoxic
      conditions. Moreover, DHA potently reduced clonogenic survival of HCT116 cells in
      normoxia and hypoxia. Treatment of HCT116 cells with 25 MUM DHA resulted in
      activation of Bax under normoxic and hypoxic conditions. Interestingly,
      cytochrome c release from the mitochondria and caspase-activation were observed
      only under normoxic conditions, whereas, under hypoxic conditions DHA induced a
      caspase-independent apoptosis-like cell death. However, under both conditions,
      generation of reactive oxygen species was an important mediator of DHA-induced
      toxicity. Further molecular analysis suggests that DHA-mediated cell death
      involves different sets of pro-apoptotic Bcl-2 family members. The pronounced
      cytotoxic activity of DHA in severe hypoxia as well as normoxia offers new
      perspectives for targeting the hypoxic tumor cell fraction to improve treatment
      outcome for cancer patients. 

PMID- 24904832
TI  - A Comparison of Techniques for (90)Y PET/CT Image-Based Dosimetry Following
      Radioembolization with Resin Microspheres.
AB  - (90)Y PET/CT following radioembolization has recently been established as a
      viable diagnostic tool, capable of producing images that are both quantitative
      and have superior image quality than alternative (90)Y imaging modalities.
      Because radioembolization is assumed to be a permanent implant, it is possible to
      convert quantitative (90)Y PET image sets into data representative of spatial
      committed absorbed-dose. Multiple authors have performed this transformation
      using dose-point kernel (DPK) convolution to account for the transport of the
      high-energy (90)Y beta-particles. This article explores a technique called the
      Local Deposition Method (LDM), an alternative to DPK convolution for (90)Y image
      based dosimetry. The LDM assumes that the kinetic energy from each (90)Y beta
      particle is deposited locally, within the voxel where the decay occurred. Using
      the combined analysis of phantoms scanned using (90)Y PET/CT and ideal
      mathematical phantoms, an accuracy comparison of DPK convolution and the LDM has
      been performed. Based on the presented analysis, DPK convolution provides no
      detectible accuracy benefit over the LDM for (90)Y PET-based dosimetry. For PET
      systems with (90)Y resolution poorer than 3.25 mm at full-width and half-max
      using a small voxel size, the LDM may produce a dosimetric solution that is more
      accurate than DPK convolution under ideal conditions; however, image noise can
      obscure some of the perceived benefit. As voxel size increases and resolution
      decreases, differences between the LDM and DPK convolution are reduced. The LDM
      method of post-radioembolization dosimetry has the advantage of not requiring
      additional post-processing. The provided conversion factors can be used to
      determine committed absorbed-dose using conventional PET image analysis tools.
      The LDM is a recommended option for routine post-radioembolization (90)Y
      dosimetry based on PET/CT imaging. 

PMID- 24904831
TI  - Prognostic Significance of beta-Catenin, E-Cadherin, and SOX9 in Colorectal
      Cancer: Results from a Large Population-Representative Series.
AB  - Robust biomarkers that can precisely stratify patients according to treatment
      needs are in great demand. The literature is inconclusive for most reported
      prognostic markers for colorectal cancer (CRC). Hence, adequately reported
      studies in large representative series are necessary to determine their clinical
      potential. We investigated the prognostic value of three Wnt signaling-associated
      proteins, beta-catenin, E-cadherin, and SOX9, in a population-representative
      single-hospital series of 1290 Norwegian CRC patients by performing
      immunohistochemical analyses of each marker using the tissue microarray
      technology. Loss of membranous or cytosolic beta-catenin and loss of cytosolic E
      cadherin protein expression were significantly associated with reduced 5-year
      survival in 903 patients who underwent major resection (722 evaluable tissue
      cores) independently of standard clinicopathological high-risk parameters. Pre
      specified subgroup analyses demonstrated particular effect for stage IV patients
      for beta-catenin membrane staining (P = 0.018; formal interaction test P =
      0.025). Among those who underwent complete resection (714 patients, 568
      evaluable), 5-year time-to-recurrence analyses were performed, and stage II
      patients with loss of cytosolic E-cadherin were identified as an independent high
      risk subgroup (P = 0.020, formal interaction test was not significant). Nuclear
      beta-catenin and SOX9 protein, regardless of intracellular location, were not
      associated with prognosis. In conclusion, the protein expression level of
      membranous or cytosolic beta-catenin and E-cadherin predicts CRC patient
      subgroups with inferior prognosis. 

PMID- 24904828
TI  - Glycobiology of neuroblastoma: impact on tumor behavior, prognosis, and
      therapeutic strategies.
AB  - Neuroblastoma (NB), accounting for 10% of childhood cancers, exhibits aberrant
      cell-surface glycosylation patterns. There is evidence that changes in
      glycolipids and protein glycosylation pathways are associated to NB biological
      behavior. Polysialic acid (PSA) interferes with cellular adhesion, and correlates
      with NB progression and poor prognosis, as well as the expression of
      sialyltransferase STX, the key enzyme responsible for PSA synthesis. Galectin-1
      and gangliosides, overexpressed and actively shedded by tumor cells, can modulate
      normal cells present in the tumor microenvironment, favoring angiogenesis and
      immunological escape. Different glycosyltransferases are emerging as tumor
      markers and potential molecular targets. Immunotherapy targeting
      disialoganglioside GD2 rises as an important treatment option. One anti-GD2
      antibody (ch14.18), combined with IL-2 and GM-CSF, significantly improves
      survival for high-risk NB patients. This review summarizes our current knowledge
      on NB glycobiology, highlighting the molecular basis by which carbohydrates and
      protein-carbohydrate interactions impact on biological behavior and patient
      clinical outcome. 

PMID- 24904833
TI  - Clinical characteristics and management of late urinary symptom flare following
      stereotactic body radiation therapy for prostate cancer.
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly utilized as
      primary treatment for clinically localized prostate cancer. While acute post-SBRT
      urinary symptoms are well recognized, the late genitourinary toxicity of SBRT has
      not been fully described. Here, we characterize the clinical features of late
      urinary symptom flare and recommend conservative symptom management approaches
      that may alleviate the associated bother. METHODS: Between February 2008 and
      August 2011, 216 men with clinically localized prostate cancer were treated
      definitively with SBRT at Georgetown University Hospital. Treatment was delivered
      using the CyberKnife with doses of 35-36.25 Gy in five fractions. The prevalence
      of each of five Common Terminology Criteria for Adverse Events (CTCAE) graded
      urinary toxicities was assessed at each follow-up visit. Medication usage was
      documented at each visit. Patient-reported urinary symptoms were assessed using
      the American Urological Association (AUA) symptom score and the Expanded Prostate
      Cancer Index Composite (EPIC)-26 at 1, 3, 6, 9, 12, 18, and 24 months. Late
      urinary symptom flare was defined as an increase in the AUA symptom score of >=5
      points above baseline with a degree of severity in the moderate to severe range
      (AUA symptom score >=15). The relationship between the occurrence of flare and
      pre-treatment characteristics were examined. RESULTS: For all patients, the AUA
      symptom score spiked transiently at 1 month post-SBRT. Of the 216 patients, 29
      (13.4%) experienced a second transient increase in the AUA symptom score that met
      the criteria for late urinary symptom flare. Among flare patients, the median age
      was 66 years compared to 70 for those without flare (p = 0.007). In patients who
      experienced flare, CTCAE urinary toxicities including dysuria, frequency/urgency,
      and retention peaked at 9-18 months, and alpha-antagonist utilization increased
      at 1 month post-treatment, rose sharply at 12 months post-treatment, and peaked
      at 18 months (85%) before decreasing at 24 months. The EPIC urinary summary score
      of flare patients declined transiently at 1 month and experienced a second, more
      protracted decline between 6 and 18 months before returning to near baseline at 2
      year post-SBRT. Statistically and clinically significant increases in patient
      reported frequency, weak stream, and dysuria were seen at 12 months post-SBRT.
      Among flare patients, 42.9% felt that urination was a moderate to big problem at
      12 months following SBRT. CONCLUSION: In this study, we characterize late urinary
      symptom flare following SBRT. Late urinary symptom flare is a constellation of
      symptoms including urinary frequency/urgency, weak stream, and dysuria that
      transiently occurs 6-18 months post-SBRT. Provision of appropriate anticipatory
      counseling and the maintenance of prophylactic alpha-antagonists may limit the
      bother associated with this syndrome.

PMID- 24904834
TI  - Size Does Matter: Why Polyploid Tumor Cells are Critical Drug Targets in the War
      on Cancer.
AB  - Tumor evolution presents a formidable obstacle that currently prevents the
      development of truly curative treatments for cancer. In this perspective, we
      advocate for the hypothesis that tumor cells with significantly elevated genomic
      content (polyploid tumor cells) facilitate rapid tumor evolution and the
      acquisition of therapy resistance in multiple incurable cancers. We appeal to
      studies conducted in yeast, cancer models, and cancer patients, which all
      converge on the hypothesis that polyploidy enables large phenotypic leaps,
      providing access to many different therapy-resistant phenotypes. We develop a
      flow-cytometry based method for quantifying the prevalence of polyploid tumor
      cells, and show the frequency of these cells in patient tumors may be higher than
      is generally appreciated. We then present recent studies identifying promising
      new therapeutic strategies that could be used to specifically target polyploid
      tumor cells in cancer patients. We argue that these therapeutic approaches should
      be incorporated into new treatment strategies aimed at blocking tumor evolution
      by killing the highly evolvable, therapy-resistant polyploid cell subpopulations,
      thus helping to maintain patient tumors in a drug sensitive state. 

PMID- 24904835
TI  - Perspectives of differentiation therapies of acute myeloid leukemia: the search
      for the molecular basis of patients' variable responses to 1,25-dihydroxyvitamin
      d and vitamin d analogs.
AB  - The concept of differentiation therapy of cancer is ~40 years old. Despite many
      encouraging results obtained in laboratories, both in vitro and in vivo studies,
      the only really successful clinical application of differentiation therapy was
      all-trans-retinoic acid (ATRA)-based therapy of acute promyelocytic leukemia
      (APL). ATRA, which induces granulocytic differentiation of APL leukemic blasts,
      has revolutionized the therapy of this disease by converting it from a fatal to a
      curable one. However, ATRA does not work for other acute myeloid leukemias
      (AMLs). Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing monocytic
      differentiation of leukemic cells, the idea of treating other AMLs with vitamin D
      analogs (VDAs) was widely accepted. Also, some types of solid cancers responded
      to in vitro applied VDAs, and hence it was postulated that VDAs can be used in
      many clinical applications. However, early clinical trials in which cancer
      patients were treated either with 1,25D or with VDAs, did not lead to conclusive
      results. In order to search for a molecular basis of such unpredictable responses
      of AML patients toward VDAs, we performed ex vivo experiments using patient's
      blast cells. Experiments were also performed using 1,25D-responsive and 1,25D-non
      responsive cell lines, to study their mechanisms of resistance toward 1,25D
      induced differentiation. We found that one of the possible reasons might be due
      to a very low expression level of vitamin D receptor (VDR) mRNA in resistant
      cells, which can be increased by exposing the cells to ATRA. Our considerations
      concerning the molecular mechanism behind the low VDR expression and its
      regulation by ATRA are reported in this paper. 

PMID- 24904836
TI  - Functions and therapeutic roles of exosomes in cancer.
AB  - The role of exosomes in cancer development has become the focus of much research,
      due to the many emerging roles possessed by exosomes. These micro-vesicles that
      are ubiquitously released in to the extracellular milieu, have been found to
      regulate immune system function, particularly in tumorigenesis, as well as
      conditioning future metastatic sites for the attachment and growth of tumor
      tissue. Through an interaction with a range of host tissue, exosomes are able to
      generate a pro-tumor environment that is essential for carcinogenesis. Herein, we
      discuss the contents of exosomes and their contribution to tumorigenesis, as well
      as their role in chemotherapeutic resistance and the development of novel cancer
      treatments and the identification of cancer biomarkers. 

PMID- 24904838
TI  - Cell-wall deficient L. monocytogenes L-forms feature abrogated pathogenicity.
AB  - Stable L-forms are cell wall-deficient bacteria which are able to multiply and
      propagate indefinitely, despite the absence of a rigid peptidoglycan cell wall.
      We investigated whether L-forms of the intracellular pathogen L. monocytogenes
      possibly retain pathogenicity, and if they could trigger an innate immune
      response. While phagocytosis of L. monocytogenes L-forms by non-activated
      macrophages sometimes resulted in an unexpected persistence of the bacteria in
      the phagocytes, they were effectively eliminated by IFN-gamma preactivated or
      bone marrow-derived macrophages (BMM). These findings were in line with the
      observed down-regulation of virulence factors in the cell-wall deficient L.
      monocytogenes. Absence of Interferon-beta (IFN-beta) triggering indicated
      inability of L-forms to escape from the phagosome into the cytosol. Moreover,
      abrogated cytokine response in MyD88-deficient dendritic cells (DC) challenged
      with L. monocytogenes L-forms suggested an exclusive TLR-dependent host response.
      Taken together, our data demonstrate a strong attenuation of Listeria
      monocytogenes L-form pathogenicity, due to diminished expression of virulence
      factors and innate immunity recognition, eventually resulting in elimination of L
      form bacteria from phagocytes. 

PMID- 24904839
TI  - Transposon mutagenesis as an approach to improved understanding of Borrelia
      pathogenesis and biology.
AB  - Transposon insertion provides a method for near-random mutation of bacterial
      genomes, and has been utilized extensively for the study of bacterial
      pathogenesis and biology. This approach is particularly useful for organisms that
      are relatively refractory to genetic manipulation, including Lyme disease
      Borrelia. In this review, progress to date in the application of transposon
      mutagenesis to the study of Borrelia burgdorferi is reported. An effective Himar1
      based transposon vector has been developed and used to acquire a sequence-defined
      library of nearly 4500 mutants in the infectious, moderately transformable B.
      burgdorferi B31 derivative 5A18NP1. Analysis of these transposon mutants using
      signature-tagged mutagenesis (STM) and Tn-seq approaches has begun to yield
      valuable information regarding the genes important in the pathogenesis and
      biology of this organism. 

PMID- 24904837
TI  - Phagosomal TLR signaling upon Borrelia burgdorferi infection.
AB  - Internalization and degradation of live Bb within phagosomal compartments of
      monocytes, macrophages and dendritic cells (DCs), allows for the release of
      lipoproteins, nucleic acids and other microbial products, triggering a broad and
      robust inflammatory response. Toll-like receptors (TLRs) are key players in the
      recognition of spirochetal ligands from whole viable organisms (i.e., vita
      PAMPs). Herein we will review the role of endosomal TLRs in the response to the
      Lyme disease spirochete. 

PMID- 24904841
TI  - A scoring method to standardize lesion monitoring following intra-dermal
      infection of Leishmania parasites in the murine ear.

PMID- 24904840
TI  - Challenges in the culture-independent analysis of oral and respiratory samples
      from intubated patients.
AB  - The spread of microorganisms in hospitals is an important public health threat,
      and yet few studies have assessed how human microbial communities (microbiota)
      evolve in the hospital setting. Studies conducted so far have mainly focused on a
      limited number of bacterial species, mostly pathogenic ones and primarily during
      outbreaks. We explored the bacterial community diversity of the microbiota from
      oral and respiratory samples of intubated patients hospitalized in the intensive
      care unit and we discuss the technical challenges that may arise while using
      culture-independent approaches to study these types of samples. 

PMID- 24904842
TI  - The role of eicosanoids in experimental Lyme arthritis.
AB  - Experimental Lyme arthritis is an inflammatory arthritis caused by infection of
      mice with the spirochete, Borrelia burgdorferi. It recapitulates many of the
      disease parameters seen in human patients with Lyme arthritis, and thus serves as
      a model system for the investigation of disease pathogenesis. While much progress
      has been made in defining components of the immune response to Borrelia
      infection, an overall understanding of the host response leading to arthritis
      resistance or susceptibility remains elusive. In this review, we will focus on
      recent advancements of our understanding of the roles of eicosanoids as
      inflammatory mediators in the regulation of experimental Lyme arthritis.
      Eicosanoids, such as PGE2 and LTB4, are powerful regulators of inflammatory
      responses and thus may be important mediators of Lyme arthritis. 

PMID- 24904843
TI  - The current state of dyslipidemia in Korean children and adolescents and its
      management in clinical practice.
AB  - Cardiovascular disease (CVD) is a leading cause of death worldwide including
      Korea. The risk factors of CVD are known as positive family history of early CVD,
      obesity, hypertension, diabetes, and dyslipidemia. Among those, dyslipidemia is
      one of modifiable risk factors. Dyslipidemia starts in childhood and progress to
      adulthood. Furthermore, dyslipidemia cause atherosclerosis and is closely related
      to other CVD risks. On the rationale that early identification and control of
      pediatric dyslipidemia will reduce the risk and severity of CVD in adulthood, the
      National Heart, Lung, and Blood Institute guidelines expanded to universal
      screening for lipid levels. However, there was no guideline for lipid screening
      and management in Korean children and adolescents yet. This review deals with the
      rationale of early identification and control of pediatric dyslipidemia along
      with the current Korean status of pediatric dyslipidemia. This review also deals
      with how to screen, diagnosis, and treatment of pediatric dyslipidemia. 

PMID- 24904844
TI  - Role of insulin-like growth factor binding protein-3 in glucose and lipid
      metabolism.
AB  - Insulin-like growth factor binding protein (IGFBP)-3 has roles in modulating the
      effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF
      independent manner. Although recent studies have been reported that IGFBP-3 has
      also roles in metabolic regulation, their exact roles in adipose tissue are
      poorly understood. In this review, we summarized the studies about the biological
      roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice
      suggested that IGFBP-3 results in glucose intolerance, and insulin resistance.
      IGFBP-3 knockout (KO) mice exhibited normal insulin level and glucose response
      after glucose challenge. More recent study in IGFBP-3 KO mice with a high-fat
      diet demonstrated that IGFBP-3 KO mice exhibited elevated fasting glucose and
      insulin, but normal response to glucose challenge, suggesting that IGFBP-3 KO
      mice may induce insulin resistance even though preserved insulin sensitivity. In
      vitro and in vivo studies using 3T3-L1 adipocytes and rat, IGFBP-3 induced
      insulin resistance by inhibiting glucose uptake. In contrast, the reduced levels
      of IGFBP-3 in obesity might induce insulin resistance by suppression of IGFBP-3's
      anti-inflammatory function, suggesting IGFBP-3 has a protective effect on insulin
      resistance. Also, proteolysis of IGFBP-3 might contribute to the insulin
      resistance in obesity and type 2 diabetes mellitus. In addition, IGFBP-3
      inhibited adipocyte differentiation, suggesting IGFBP-3 may contribute to the
      insulin insensitivity. Taken together, it is not yet certain that IGFBP-3 has a
      protective effect or enhancing effect on insulin resistance, and more studies
      will be needed to clarify the roles of IGFBP-3 in metabolic regulation. 

PMID- 24904845
TI  - Response to three years of growth hormone therapy in girls with Turner syndrome.
AB  - PURPOSE: Short stature is the most common finding in patients with Turner
      syndrome. Improving the final adult height in these patients is a challenge both
      for the patients and physicians. We investigated the clinical response of
      patients to growth hormone treatment for height improvement over the period of
      three years. METHODS: Review of medical records from 27 patients with Turner
      syndrome treated with recombinant human growth hormone for more than 3 years was
      done. Differences in the changes of height standard deviation scores according to
      karyotype were measured and factors influencing the height changes were analyzed.
      RESULTS: The response to recombinant human growth hormone was an increase in the
      height of the subjects to a mean value of 1.1 standard deviation for subjects
      with Turner syndrome at the end of the 3-year treatment. The height increment in
      the first year was highest. The height standard deviation score in the third year
      was negatively correlated with the age at the beginning of the recombinant human
      growth hormone treatment. Different karyotypes in subjects did not seem to affect
      the height changes. CONCLUSION: Early growth hormone administration in subjects
      with Turner syndrome is helpful to improve height response to the treatment.

PMID- 24904846
TI  - Different clinical courses of central precocious girls according to their age at
      presentation and treatment.
AB  - PURPOSE: The progressivity of central precocious puberty (CPP) seems to depend on
      the age at presentation. We evaluated the clinical courses of CPP girls according
      to their age at initiation of treatment. METHODS: One hundred thirty five girls
      with CPP diagnosed between Jan. 2003 and Dec. 2009 and regularly followed for
      more than one year were included. They were treated with gonadotropin-releasing
      hormone agonists (GnRHa) every four weeks. Subjects were divided into two groups
      based on whether they were treated before (Group I, N=20) or after seven years of
      age (Group II, N=115). We compared the anthropometric parameters, the predicted
      adult height (PAH), predicted treatment periods, and the laboratory findings of
      the two groups every six months. RESULTS: Out of 135 CPP patients, 123 were
      idiopathic and twelve had neurogenic problems. At the baseline, patients' average
      bone age (BA) was significantly older than chronologic age (CA) and PAH was
      significantly shorter than target height (TH). BA and CA were significantly older
      in group II, but the BA/CA ratio was significantly greater in group I. The
      average treatment period required to overcome the CA-BA difference was 4.64 yr
      (group I vs II; 7.98 yr vs 4.24 yr, P < 0.01), and the period needed to overcome
      PAH-TH difference was 2.49 yr (group I vs II; 4.37 yr vs 2.32 yr, P < 0.01).
      CONCLUSION: Among the girls with CPP, the younger age group had more advanced BA
      than CA, and needed significantly longer treatment periods to overcome the BA-CA
      gap and PAH-TH gaps.

PMID- 24904847
TI  - Combined aerobic and resistance exercise is effective for achieving weight loss
      and reducing cardiovascular risk factors without deteriorating bone health in
      obese young adults.
AB  - PURPOSE: Weight loss reduces cardiovascular risk factors in the obese. However,
      weight reduction through diet negatively affects long-term bone health. The aim
      of study was to determine the ability of combined aerobic and resistance exercise
      (CE) to reduce weight and cardiovascular risk without diminishing bone health.
      METHODS: Twenty-five young adults participated in an 8-week weight loss CE
      program. Subjects were allocated to an obese group or a control group by body
      mass index (BMI). Body weight, BMI, body composition, and bone mineral density
      (BMD) of the lumbar spine and total hip were measured before and after the CE
      trial. Serum levels of metabolic markers, including adipokines and bone markers,
      were also evaluated. RESULTS: Weight loss was evident in the obese group after
      the 8 weeks CE trial. Fat mass was significantly reduced in both groups. Fasting
      insulin, homeostatic model assessment-insulin resistance (HOMA-IR), leptin and
      aminotransferases level were significantly reduced from baseline only in the
      obese group. High density lipoprotein cholesterol increased in both groups. Hip
      BMD increased in the obese group. In all study subjects, BMI changes were
      correlated with HOMA-IR, leptin, and HDL changes. BMI decreases were correlated
      with lumbar spine BMD increases, lumbar spine BMD increases were positively
      correlated with osteocalcin changes, and lumbar spine bone mineral content
      increases were correlated negatively with C-terminal telopeptide of type 1
      collagen changes. CONCLUSION: These findings suggest that CE provides effective
      weight loss and improves cardiovascular risk factors without diminishing BMD.
      Furthermore, they indicate that lumbar spine BMD might be maintained by
      increasing bone formation and decreasing bone resorption.

PMID- 24904848
TI  - Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves'
      disease.
AB  - Hypoglycemia was detected in a 15-year-old girl due to loss of consciousness. She
      was diagnosed with Graves' disease and was being treated with methimazole for the
      past 4 months. A paradoxically increased insulin levels was found when she
      suffered from the hypoglycemic episode. An imaging study showed no mass lesion in
      the pancreas, and insulin antibodies were found in the serum. She was diagnosed
      with insulin autoimmune syndrome. Her HLA typing was performed, and it revealed
      HLA-DRB1 (*)04:06. The patient was treated with a corticosteroid for 2 months.
      After discontinuing the steroid, the insulin antibody titer decreased
      dramatically, and she did not have any episode of hypoglycemia since. This is the
      first report of insulin autoimmune syndrome in a Korean girl, and we have
      revealed the connection between HLA type and insulin autoimmune syndrome in
      Korea. 

PMID- 24904849
TI  - Gitelman syndrome combined with complete growth hormone deficiency.
AB  - Gitelman syndrome is a rare autosomal recessive hereditary salt-losing
      tubulopathy, that manifests as hypokalemic metabolic alkalosis, hypomagnesemia,
      and hypocalciuria. It is caused by mutations in the solute carrier family
      12(sodium/chloride transporters), member 3 (SLC12A3) gene encoding the thiazide
      sensitive sodium chloride cotransporter channel (NCCT) in the distal convoluted
      tubule of the kidney. It is associated with muscle weakness, cramps, tetany,
      vomiting, diarrhea, abdominal pain, and growth retardation. The incidence of
      growth retardation, the exact cause of which is unknown, is lower than that of
      Bartter syndrome. Herein, we discuss the case of an overweight 12.9-year-old girl
      of short stature presenting with hypokalemic metabolic alkalosis. The patient, on
      the basis of detection of a heterozygous mutation in the SLC12A3 gene and poor
      growth hormone (GH) responses in two provocative tests, was diagnosed with
      Gitelman syndrome combined with complete GH deficiency. GH treatment accompanied
      by magnesium oxide and potassium replacement was associated with a good clinical
      response. 

PMID- 24904850
TI  - p.R182C mutation in Korean twin with congenital lipoid adrenal hyperplasia.
AB  - Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of
      congenital adrenal hyperplasia which is caused by mutations in the steroidogenic
      acute regulatory protein (StAR). The mutations in StAR gene resulted in failure
      of the transport cholesterol into mitochondria for steroidogenesis in the adrenal
      gland. Twin sisters (A, B) with normal 46, XX were born at 36+2 gestational week,
      premature to nonrelated parents. They had symptoms as hyperpigmentation, slightly
      elevated potassium level and low level of sodium. Laboratory finding revealed
      normal 17-hydroxyprogesterone level, elevated adrenocorticotropin hormone (A,
      4,379.2 pg/mL; B, 11,616.1 pg/mL), and high plasma renin activity (A, 49.02
      ng/mL/hr; B, 52.7 ng mL/hr). However, the level of plasma cortisol before
      treatment was low (1.5 ug/dL) in patient B but normal (8.71 ug/dL) in patient A.
      Among them, only patient A was presented with adrenal insufficiency symptoms
      which was suggestive of CLAH and prompted us to order a gene analysis in both
      twin. The results of gene analysis of StAR in twin revealed same heterozygous
      conditions for c.544C>T (Arg182Cys) in exon 5 and c.722C>T (Gln258(*)) in exon 7.
      We report the first case on the mutation of p.R182C in exon 5 of the StAR gene in
      Korea. 

PMID- 24904851
TI  - The pleiomorphic actions of vitamin D and its importance for children.
AB  - Knowledge regarding the physiological role and dietary requirements of vitamin D
      has dramatically expanded over the past several decades. The "new" vitamin D is
      not only a mediator of calcium homeostasis, it also has important
      immunomodulatory, antimicrobial, and antiproliferative actions. In spite of the
      interest in vitamin D as a mediator in many chronic diseases of adulthood such as
      cancer and type II diabetes, less attention has been given to the implications of
      the new understanding of vitamin D for child and adolescent health. Recently,
      rickets caused by vitamin D deficiency is resurging in developed countries.
      Therefore, pharmacokinetic studies and epidemiologic research that incorporates
      clinical and functional outcomes are needed to clarify the role of vitamin D in
      growth and development in Korean children and adolescents and to determine
      vitamin D dietary requirements. 

PMID- 24904852
TI  - Kisspeptin/G protein-coupled receptor-54 system as an essential gatekeeper of
      pubertal development.
AB  - Puberty is the end-point of a complex series of developmental events, defined by
      the dynamic interaction between genetic factors and environmental cues,
      ultimately leading to the attainment of reproductive capacity. Kisspeptins,
      products of the KISS1 gene, were originally identified as metastasis suppressor
      peptides with the ability to bind G protein-coupled receptors (GPR54). In 2003,
      loss-of-function mutations of the GPR54 gene were found in patients with
      hypogonadotropic hypogonadism. This finding triggered study of the role of the
      kisspeptin/GPR54 system as an essential gatekeeper of control of reproduction and
      pubertal development. Kisspeptins are very potent elicitors of gonadotropin
      secretion, primarily through stimulation of gonadotropin-releasing hormone
      release. KISS1 also functions as an essential integrator for peripheral inputs,
      including gonadal steroids and nutritional signals, and for controlling GnRH and
      gonadotropin secretion. Whether the kisspeptin/GPR54 system is the trigger for
      puberty onset and/or it operates as integrator and effector of up-stream
      regulatory factors warrants further investigation. 

PMID- 24904853
TI  - Age at menarche in the Korean female: secular trends and relationship to
      adulthood body mass index.
AB  - PURPOSE: The objective of this study is to estimate the trend in age at menarche
      in the Korean female and evaluate the relationship between age at menarche and
      adult body mass index (BMI), which is a indicator of later-life health. METHODS:
      We conducted a cross-sectional analysis of a nationally representative sample
      (self-reported age at menarche and measured height and weight) of 11,065 females
      aged 15 and older. Data were obtained from the Fourth Korea National Health and
      Nutrition Examination Survey (KNHANES IV, 2007-2009). RESULTS: We found a
      statistically significant decline in age at menarche in successive birth groups,
      indicating a 0.726 year decrease per decade. The age at menarche in 1990-1994
      year birth group was 12.60 years, which showed a significant decreased from 3.11
      years in the 1980-1984 birth group. We also found a significant negative
      association between age at menarche and current BMI. A one-year decrease in age
      at menarche was associated with mean BMI increase of 0.109 kg/m(2) (95%
      confidence interval [CI], 0.069 to 0.150) after adjustment for age. In
      multivariate logistic regression, the odds ratios of obesity in females with
      early menarche (<12 years) was 1.845 fold (95% CI, 1.441 to 2.361). CONCLUSION:
      We found that age at menarche is still falling in the Korean female. We also
      found that early menarche is a risk factor for obesity in adults.

PMID- 24904854
TI  - Comparison of the prevalence of islet autoantibodies according to age and disease
      duration in patients with type 1 diabetes mellitus.
AB  - PURPOSE: This study investigated the prevalence of islet autoantibodies in
      children and adults with T1DM according to their age and the duration of disease.
      METHODS: We measured the levels of islet autoantibodies, including antiglutamic
      acid decarboxylase antibody (anti-GAD Ab), and combined these with anthropometric
      measurements and laboratory tests of 137 patients newly diagnosed with T1DM
      during the last 20 years. The subjects were subdivided into four groups according
      to their age at the onset of the disease. We then compared the prevalence of
      islet autoantibodies in the different age groups with the duration of disease.
      RESULTS: Among the 137 patients, 68.9% tested positive for islet autoantibodies
      (71.4% within 1 year; 67.7% after 1 year of the disease onset). Within 1 year of
      the onset of the disease, 66.3% of the patients were positive for the anti-GAD
      Ab, and 35.6% were positive for IAAs. The prevalence of islet autoantibodies was
      significantly higher in the prepubertal groups than in the postpubertal groups
      (80.0% vs. 58.3%). The rate of positive islet autoantibodies changed with the
      duration of disease, and it differed according to the type of autoantibody and
      the age of the patient. CONCLUSION: The rates of positive islet autoantibodies
      were significantly higher in younger than in older patients at the time of the
      diagnosis of the disease. The positive rates were significantly changed 1 year
      after the onset of the disease in the preschool and the children groups. So these
      findings suggest that we need to diagnose type 1B diabetes distinguished T2DM in
      aldolescent group, carefully.

PMID- 24904855
TI  - Estrogen receptor alpha polymorphism in boys with constitutional delay of growth
      and puberty.
AB  - PURPOSE: There were a lot of reports regarding associations of polymorphisms in
      the estrogen receptor alpha (ESR1). with many disorders. But, those with
      constitutional delay of growth and puberty (CDGP) are not known. Our aim is to
      find out any association between CDGP and ESR1. METHODS: In a total of 27
      subjects, we compared 7 CDGP patients with 20 healthy controls with their heights
      and sexual maturity rates were within normal range. We selected three single
      nucleotide polymorphisms from intron 1 of ESR1 (rs3778609, rs12665044, and
      rs827421) as candidates, respectively. RESULTS: In genotype analyses, the
      frequency of G/G genotype at rs827421 in intron 1 of ESR1 was increased in CDGP
      boys (P=0.03). CONCLUSION: The genetic variation of ESR1 can be a contributing
      factor of tempo of growth and puberty.

PMID- 24904856
TI  - Age at menarche and adult height in girls born small for gestational age.
AB  - PURPOSE: The aim of this study was to evaluate the association between birth
      characteristics based on birth weight for gestational age, timing of menarche and
      adult height in girls born small for gestational age (SGA). METHODS: Thirty
      subjects born from 1988 through 1999 whose birth weight below 10th percentile for
      their gestational ages were recruited based on hospital chart reviews. The age of
      each subject at menarche was recorded, and the subject's heights and bone age
      were assessed. RESULTS: The adult height of the girls born SGA was significantly
      lower than the normal adult height and slightly shorter than their target height.
      The adult height was associated with the birth weight for gestational age. The
      age at menarche was not different with the menarche timing of the general
      population. CONCLUSION: More attention may need to be paid to the growth outcomes
      of SGA patients whose birth weight is lower for their gestational age than other
      SGA subjects.

PMID- 24904857
TI  - Sex hormone binding globulin, free estradiol index, and lipid profiles in girls
      with precocious puberty.
AB  - PURPOSE: Sex hormone-binding globulin (SHBG) modulates the availability of
      biologically active free sex hormones. The regulatory role of SHBG might be
      important in the relationship between hormone levels and the modification of
      lipid profiles in girls with precocious puberty. However, few studies have
      evaluated the relationship of SHBG, free estradiol index (FEI), and lipid levels
      in these girls. METHODS: One hundred and nine girls less than 8 years of age with
      pubertal development were enrolled. FEI was calculated with SHBG and estradiol
      (E2). We analyzed SHBG between peak luteinizing hormone (LH)>=5 (IU/L) (group 1)
      and LH<5 (IU/L) (group 2) through a gonadotropin releasing hormone stimulation
      test. RESULTS: Body mass index (BMI) standard deviation score (SDS) was higher in
      group 2 than in group 1 (P=0.004). Serum SHBG levels did not differ and FEI was
      not higher in group 1 (P=0.122). Serum cholesterol, HDL, and LDL did not differ;
      however, triglyceride levels were higher in group 2 (P=0.023). SHBG was
      negatively correlated with bone age advancement, BMI, BMI SDS, and FEI, and was
      positively correlated with HDL. However, SHBG was not correlated with E2 or peak
      LH. CONCLUSION: Serum SHBG itself might not be associated with precocious puberty
      in girls, but it might be related to BMI and lipid profiles. Further studies are
      needed to reveal the relationship between sex hormone and obesity in girls with
      precocious puberty.

PMID- 24904858
TI  - Turner syndrome with primary hyperparathyroidism.
AB  - Turner syndrome has multiple comorbidities such as osteoporosis, obesity,
      diabetes, hypothyroidism, and hypertension. As they are treatable conditions in
      Turner syndrome, early recognition and proper treatment should be needed. We
      report on a 23-year-old woman with Turner syndrome who presented with severe
      osteoporosis and hypercalcemia. Laboratory tests showed elevated levels of serum
      calcium and parathyroid hormone. Dual-energy X-ray absorptiometry showed severe
      osteopo-rosis (z score, -3.5). Ultrasound and (99m)Tc scintigraphy of parathyroid
      glands showed an adenoma in the right inferior gland. She was diagnosed with
      primary hyperparathyroidism due to an adenoma of the parathyroid gland. After
      excision of the adenoma, the patient's serum calcium and parathyroid hormone
      levels returned to normal. Although only a few cases of Turners syndrome with
      primary hyperparathyroidism have been reported, hyperparathyroidism should be
      considered in cases of Turner syndrome with severe osteoporosis and
      hypercalcemia. 

PMID- 24904859
TI  - Central precocious puberty in a patient with X-linked adrenal hypoplasia
      congenita and Xp21 contiguous gene deletion syndrome.
AB  - X-linked adrenal hypoplasia congenita is caused by the mutation of DAX-1 gene
      (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome
      X, gene 1), and can occur as part of a contiguous gene deletion syndrome in
      association with glycerol kinase (GK) deficiency, Duchenne muscular dystrophy and
      X-linked interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) gene
      deficiency. It is usually associated with hypogonadotropic hypogonadism, although
      in rare cases, it has been reported to occur in normal puberty or even central
      precocious puberty. This study addresses a case in which central precocious
      puberty developed in a boy with X-linked adrenal hypoplasia congenita who had
      complete deletion of the genes DAX-1, GK and IL1RAPL1 (Xp21 contiguous gene
      deletion syndrome). Initially he was admitted for the management of adrenal
      crisis at the age of 2 months, and managed with hydrocortisone and florinef. At
      45 months of age, his each testicular volumes of 4 mL and a penile length of 5 cm
      were noted, with pubic hair of Tanner stage 2. His bone age was advanced and a
      gonadotropin-releasing hormone (GnRH) stimulation test showed a luteinizing
      hormone peak of 8.26 IU/L, confirming central precocious puberty. He was then
      treated with a GnRH agonist, as well as steroid replacement therapy. In Korea,
      this is the first case of central precocious puberty developed in a male patient
      with X-linked adrenal hypoplasia congenita. 

PMID- 24904860
TI  - Hyponatremia caused by excessive intake of water as a form of child abuse.
AB  - Hyponatremia is the most common electrolyte disorder that requires careful
      management. Water intoxication with hyponatremia is rare condition that
      originated from overhydration. Water intoxication, also known as dilutional
      hyponatremia, develops only because the intake of water exceeds the kidney's
      ability to eliminate water. Causes of this water intoxication include psychiatric
      disorder, forced water intake as a form of child abuse and iatrogenic infusion of
      excessive hypotonic fluid. We experienced and reported a case of symptomatic
      hyponatremia by forced water intake as a form of child abuse. 

PMID- 24904861
TI  - Genetic syndromes associated with overgrowth in childhood.
AB  - Overgrowth syndromes comprise a diverse group of conditions with unique clinical,
      behavioral and molecular genetic features. While considerable overlap in
      presentation sometimes exists, advances in identification of the precise etiology
      of specific overgrowth disorders continue to improve clinicians' ability to make
      an accurate diagnosis. Among them, this paper introduces two classic genetic
      overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome.
      Historically, the diagnosis was based entirely on clinical findings. However, it
      is now understood that Sotos syndrome is caused by a variety of molecular genetic
      alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35
      and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in
      the imprinting of a number of growth regulatory genes within chromosome 11p15 in
      the majority of cases. Interestingly, the 11p15 imprinting region is also
      associated with Russell-Silver syndrome which is a typical growth retardation
      syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical
      features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome.
      Although the exact functions of the causing genes have not yet been completely
      understood, these overgrowth syndromes can be good models to clarify the complex
      basis of human growth and help to develop better-directed therapies in the
      future. 

PMID- 24904862
TI  - Diabetes care for emerging adults: transition from pediatric to adult diabetes
      care systems.
AB  - With the increasing prevalence of diabetes mellitus in children, transitioning
      patients from childhood to adulthood are increasing. High-risk behaviors and poor
      glycemic control during the transition period increase the risk for hypoglycemia
      and hyperglycemia as well as chronic microvascular and macrovascular
      complications. Discussions regarding complications and preparations for
      transition must take place before the actual transition to adult care systems.
      Pediatric care providers should focus on diabetes self-management skills and
      prepare at least 1 year prior to the transfer. Pediatric providers should also
      provide a written summary about previous and current glycemic control,
      complications and the presence of mental health problems such as disordered
      eating behaviors and affective disorders. Transition care should be
      individualized, with an emphasis on diabetes self-management to prevent acute and
      long-term complications. Regular screening and management of complications should
      proceed according to pediatric and adult guidelines. Birth control, use of
      alcohol, smoking and driving should also be discussed. Barriers to self
      management and care must be recognized and solutions sought. The goals of
      transitional care are to effectively transition the diabetic patient from the
      pediatric to adult care system with less elapsed time in between and to improve
      post-transition outcome. Previous studies regarding diabetes transitional care
      programs including patient education programs, medical coordinators and auxiliary
      service systems reported promising results. However, there is a lack of evidence
      regarding best practices in transition care. Further studies are needed to
      provide evidence based transitional care programs that take both medical and
      psychosocial aspects of diabetes care into consideration. 

PMID- 24904863
TI  - Various endocrine disorders in children with t(13;14)(q10;q10) Robertsonian
      translocation.
AB  - PURPOSE: 45,XY,t(13;14)(q10;q10) karyotype can suggest infertility associated
      with more or less severe oligospermia in male adults. In addition,
      45,XX,t(13;14)(q10;q10) karyotype carries reproductive risks such as miscarriage
      or infertility in female adults. However, reports on the phenotype of this
      karyotype in children are very rare. This study was done to observe various
      phenotypes of this karyotype in children. METHODS: Between January 2007 and
      December 2012, children diagnosed with 45,XY,t(13;14)(q10;q10) or
      45,XX,t(13;14)(q10;q10) karyotype by chromosome analysis were analyzed
      retrospectively. RESULTS: Eight children (5 boys and 3 girls) were diagnosed with
      45,XY,t(13;14)(q10;q10) or 45,XX,t(13;14)(q10;q10) karyotype. They ranged in age
      from 5 years and 6 months to 12 years and 4 months. The phenotypes of the study
      patients consisted of 1 hypogonadotrophic hypogonadism, 1 precocious puberty, 3
      early puberty, 2 growth hormone deficiency (GHD) (partial) and 1 idiopathic short
      stature. As shown here t(13;14)(q10;q10) Robertsonian translocation shows a wide
      range of phenotypes. CONCLUSION: It can be said that t(13;14)(q10;q10)
      Robertsonian translocation shows various phenotypes from GHD to precocious
      puberty in children. Further large-scale studies are necessary.

PMID- 24904864
TI  - Relationship of age at menarche on anthropometric index and menstrual
      irregularity in late adolescent girls in Seoul.
AB  - PURPOSE: To examine the relationship between menarcheal age and anthropometric
      indices and menstrual irregularity in late adolescent girls in Seoul. METHODS: We
      surveyed 4,218 fertile adolescent girls between the ages of 16 and 18 years to
      determine their anthropometric indices and menarcheal age. Measurements were
      taken from June 2008 to October 2009 at seven girl's high schools in Seoul,
      Korea. Participants were offered self-report questionnaire as a survey tool that
      included questions on anthropometric indices (height, weight, waist
      circumference), menarcheal age, menstrual pattern, frequency of menstruation per
      year. RESULTS: THE PARTICIPANTS WERE CATEGORIZED INTO THREE GROUPS BASED ON
      MENARCHEAL AGE: early menarche group (younger than 2 standard deviations [SD]),
      mid menarche group (within +/-2 SD), late menarche group (older than 2 SD). The
      mean age of early menarche group was 9.9+/-0.2 years, mid menarche group 12.5+/
      0.9 years, late menarche group 15.1+/-0.3 years (P < 0.001). Heights were
      recorded as 160.4+/-5.2 cm, 161.8+/-4.9 cm, 162.3+/-4.7 cm in early, mid, and
      late menarche group, respectively (P = 0.001). Body mass index (BMI) and waist
      circumference significantly were lager in early menarche group than mid and late
      menarche ones (P < 0.001). The menarcheal age had a positive correlation with
      height and negative correlations with weight, BMI, waist circumference (P <
      0.001). The prevalence of oligomenorrhea was more frequent in late menarche group
      than early and mid menarche group. CONCLUSION: The menarcheal age have positive
      relationship with height and inverse relationship with BMI and waist
      circumference in late adolescent girls in Seoul. Late menarcheal girls are
      disposed to have menstrual irregularity compared to early menarcheal girls.

PMID- 24904865
TI  - Psychological characteristics of Korean children and adolescents with type 1
      diabetes mellitus.
AB  - PURPOSE: This study investigates the behavioral and emotional characteristics of
      Korean children and adolescents with type 1 diabetes mellitus (T1DM) as compared
      to healthy controls, and examines whether their psychological status is
      associated with glycemic control, insulin regimens, or disease duration. METHODS:
      A total of 37 Korean children and adolescents with T1DM, aged 6-17 years, and 38
      sex- and age-matched healthy controls were included in this study. Psychological
      distress was assessed using the Korean child behavior checklist (K-CBCL) and
      children's depression inventory (CDI) after the subjects and their parents were
      interviewed. RESULTS: The CDI and K-CBCL scores were significantly higher in T1DM
      subjects compared to normal controls. The T1DM subjects with "poorly controlled"
      blood glucose (glycosylated hemoglobin >=8%) and "old patients" (disease duration
      >=1 year) had a tendency to show higher CDI and K-CBCL scores. There were no
      significant differences in CDI and K-CBCL scores between the intensive and
      conventional insulin therapy groups. CONCLUSION: Children and adolescents with
      T1DM seem to have inferior psychological adjustment to their normal counterparts,
      which might be associated with glycemic control and disease duration.
      Psychological evaluation and intervention should be considered in the management
      of T1DM in children and adolescents.

PMID- 24904866
TI  - Genotype-phenotype correlation in 27 pediatric patients in congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency in a single center.
AB  - PURPOSE: The purpose of the study was to evaluate endocrine patterns of patients
      with congenital adrenal hyperplasia and each gene mutation and to analyze the
      correlation between each phenotype and genotype. METHODS: This was a
      retrospective study of the patients with congenital adrenal hyperplasia in the
      pediatric outpatient clinic at the Samsung Medical Center from November 1994 to
      December 2012. We analyzed the medical records of 27 patients (male, 19; female,
      8) with congenital adrenal hyperplasia who had been diagnosed by genetic testing
      to have 21-hydroxylase deficiency. RESULTS: In genetic analysis of 54 alleles
      from 27 patients, 13 types of mutations were identified. The distribution of 21
      hydroxylase deficiency gene mutations revealed that intron 2 splice site (c.293
      13A/C>G) mutations and large deletions were the most common, at 31.5% and 22.2%
      respectively, followed by p.I173N, p.R356W, and p.I172N mutations at 11.1%, 9.3%,
      and 9.3%, respectively. Other mutations were observed at 1.9-3.7%. No novel
      mutations were detected. CONCLUSION: The analysis of 54 alleles revealed 13 types
      of mutation. The salt wasting form showed a good correlation between genotype and
      phenotype, but the simple virilizing and nonclassic forms showed inconsistencies
      between genotype and phenotype. The distribution of CYP21A2 mutations was
      evaluated for 21-hydroxylase deficiency patients from a single center. This study
      provides limited data on mutation spectrum and genotype-phenotype correlation of
      21-hydroxylase deficiency in Korea.

PMID- 24904867
TI  - Depression and self-concept in girls with perception of pubertal onset.
AB  - PURPOSE: Early pubertal timing in girls is associated with psychological and
      behavioral problems. This study aimed to evaluate the psychological features of
      girls who perceived breast development beginning by analyzing their depression
      levels and self-concept. METHODS: From March 2007 to December 2012, 93 girls were
      enrolled and assigned to a pre-8 (younger than 8 years, n=43) or post-8 (8 years
      and older, n=50) group according to the age at onset of perceived breast
      development, and their height, body weight, body mass index, bone age (BA),
      Tanner stage, and luteinizing hormone and follicle-stimulating hormone levels
      were examined. We investigated their psychological state with the Korean
      Children's Depression Inventory (CDI) and Piers-Harris Children's Self-Concept
      Scale (PHCSC) to evaluate depression levels and self-concept, respectively.
      RESULTS: The pre-8 group had a significantly greater height standard deviation
      score, (0.5+/-1.01 vs. 0.11+/-0.86, P = 0.048) and more advanced BA (2.07+/-1.02
      years vs. 1.40+/-0.98 years, P = 0.004) compared to the post-8 group. There were
      no statistically significant intergroup differences for the CDI and PHCSC scores;
      however, the pre-8 group scored higher than the post-8 group in the physical
      appearance and attributes domain of the PHCSC (9.93+/-2.57 vs. 8.52+/-3.03, P =
      0.017). CONCLUSION: The timing of perceived breast development among girls who
      thought puberty to begin did not affect depression levels and self-concept. There
      was no correlation between Tanner stage and depression levels and self-concept
      despite the perception of pubertal onset. The pre-8 group had a more positive
      view of their physical appearance than the post-8 group.

PMID- 24904868
TI  - Serum ferritin level is higher in male adolescents with obesity: results from the
      Korean National Health and Nutrition Examination Survey 2010.
AB  - PURPOSE: Previous reports show an association between high serum ferritin levels
      and metabolic syndrome (MS) in adults. In adolescents, little information is
      available with obesity and serum ferritin levels. METHODS: This is a cross
      sectional study. Data were obtained from the 5th Korean National Health and
      Nutrition Examination Survey (K-NHANES) conducted during 2010 by the Korean
      Ministry of Health and Welfare. A total of 849 subjects aged 10-18 years
      participated in the 2010 survey. A body mass index (BMI) >=95th percentile for
      age and sex or a BMI >=25 was used to diagnose as obesity. RESULTS: The weighted
      prevalence of obesity was 13.4% (62/462) in male and 8.5% (33/387) in female. We
      observed significantly higher serum ferritin in male than in female (mean+/
      standard error [SE], 50.5+/-2.3 uU/L vs. 30.6+/-1.3 uU/L; P<0.0001). In male,
      serum ferritin is positively correlated with age (P<0.0001). White blood cell
      (WBC) count, serum fasting blood sugar, triglyceride (TG), total cholesterol, low
      density lipoprotein, insulin, homeostasis model assessment-insulin resistance
      (HOMA-IR), systolic and diastolic blood pressure, and ferritin levels were higher
      and high-density lipoprotein (HDL) were lower in the obesity than in the normal
      group. In female adolescents, WBC count, TG, insulin, and HOMA-IR were higher and
      HDL were lower in the obesity than in the normal group. In male, serum ferritin
      levels showed positive association with obesity (beta=21.196, P=0.016).
      CONCLUSION: Serum ferritin levels appear to be associated with obesity in Korean
      male adolescents.

PMID- 24904869
TI  - Insulin pump therapy in transient neonatal diabetes mellitus.
AB  - Neonatal diabetes mellitus (NDM) is a rare disease requiring insulin treatment.
      Its treatment is primarily focused on maintaining adequate glycemic control and
      avoiding hypoglycemia. Although insulin pump therapy is frequently administered
      to adults and children, there is no consensus on the use of insulin pumps in NDM.
      A 10 day-old female infant was referred to us with intrauterine growth
      retardation and poor weight gain. Hyperglycemia was noted, and continuous
      intravenous insulin infusion was initiated. However, the patient's serum glucose
      levels fluctuated widely, and maintaining the intravenous route became difficult
      within the following weeks. Continuous subcutaneous insulin infusion with an
      insulin pump was introduced on the twenty-fifth day of life, and good glycemic
      control was achieved without any notable adverse effects including hypoglycemia.
      We suggest that the insulin pump is a safe and effective mode for treating NDM
      and its early adoption may shorten the length of hospital stays in patients with
      NDM. 

PMID- 24904870
TI  - Refractory rickets caused by mild distal renal tubular acidosis.
AB  - Type I (distal) renal tubular acidosis (RTA) is a disorder associated with the
      failure to excrete hydrogen ions from the distal renal tubule. It is
      characterized by hyperchloremic metabolic acidosis, an abnormal increase in urine
      pH, reduced urinary excretion of ammonium and bicarbonate ions, and mild
      deterioration in renal function. Hypercalciuria is common in distal RTA because
      of bone resorption, which increases as a buffer against metabolic acidosis. This
      can result in intractable rickets. We describe a case of distal RTA with
      nephrocalcinosis during follow-up of rickets in a patient who presented with
      clinical manifestations of short stature, failure to thrive, recurrent vomiting,
      dehydration, and irritability. 

PMID- 24904871
TI  - Pathophysiology and clinical characteristics of hypothalamic obesity in children
      and adolescents.
AB  - The hypothalamus plays a key role in the regulation of body weight by balancing
      the intake of food, energy expenditure, and body fat stores, as evidenced by the
      fact that most monogenic syndromes of morbid obesity result from mutations in
      genes expressed in the hypothalamus. Hypothalamic obesity is a result of
      impairment in the hypothalamic regulatory centers of body weight and energy
      expenditure, and is caused by structural damage to the hypothalamus,
      radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R
      and CART genes. The pathophysiology includes loss of sensitivity to afferent
      peripheral humoral signals, such as leptin, dysregulated insulin secretion, and
      impaired activity of the sympathetic nervous system. Dysregulation of 11beta
      hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the
      development of hypothalamic obesity. Intervention of this complex entity requires
      simultaneous targeting of several mechanisms that are deranged in patients with
      hypothalamic obesity. Despite a great deal of theoretical understanding,
      effective treatment for hypothalamic obesity has not yet been developed.
      Therefore, understanding the mechanisms that control food intake and energy
      homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of
      the development of new treatments options. Early identification of patients at
      risk can relieve the severity of weight gain by the provision of dietary and
      behavioral modification, and antiobesity medication. This review summarizes
      recent advances of the pathophysiology, endocrine characteristics, and treatment
      strategies of hypothalamic obesity. 

PMID- 24904872
TI  - Reduced male fertility in childhood cancer survivors.
AB  - With advances in cancer treatment, more pediatric cancer patients have increased
      their life expectancy. Because cancer-related therapy causes various physical and
      psychological problems, many male survivors experience later problems with
      thyroid and sexual functions, and with growth. As outcomes have improved, more
      survivors need to maintain their reproductive function to maximize their long
      term quality of life. Cancer and cancer-related treatment can impair fertility by
      damage to the testes, to the hypothalamic-pituitary-gonadal axis, or to the
      genitourinary organs. Prior radiation therapy to the testes, the use of
      alkylating agents, and central hypogonadism further impair fertility in male
      survivors of childhood cancer. Following any course of chemotherapy, peripubertal
      maturation, any testicular volume changes, and symptoms of androgen deficiency
      should be monitored systematically. If patients request fertility testing,
      spermatogenesis status can be evaluated either directly by semen analysis or
      indirectly by determination of the levels of testosterone/gonadotropins and by
      monitoring any changes in testicular volume. According to the patient's
      condition, semen cryopreservation, hormonal therapy, or assisted reproduction
      technologies should be provided. 

PMID- 24904873
TI  - Multicenter clinical trial of leuprolide acetate depot (Luphere depot 3.75 mg)
      for efficacy and safety in girls with central precocious puberty.
AB  - PURPOSE: We evaluated the efficacy, safety and psychological aspect of monthly
      administrations of the gonadotropin-releasing hormone agonists (GnRHa),
      leuprolide acetate depot (Luphere depot 3.75 mg), in patients with precocious
      puberty. METHODS: A total of 54 girls with central precocious puberty were
      administered with leuprolide acetate (Luphere depot 3.75 mg) every four weeks
      over 24 weeks. We evaluated the percentage of children exhibiting a suppressed
      luteinizing hormone (LH) response to GnRH (LH peak<=3 IU/L), peak LH/follicle
      stimulating hormone (FSH) ratio of GnRH stimulation test less than 1, change in
      bone age/chronologic age ratio, change in the Tanner stage and change in eating
      habit and psychological aspect. RESULTS: (1) The percentage of children
      exhibiting a suppressed LH response to GnRH, defined as an LH peak<=3 IU/L at 24
      weeks was 96.3 % (52/54). (2) The percentage of children exhibiting peak LH/FSH
      ratio<1 at 24 weeks of the study was 94.4 % (51/54). (3) The ratio of bone age
      and chronological age significantly declined from 1.27+/-0.07 to 1.24+/-0.01
      after the 6 months of the study. (4) The mean Tanner stage manifested a
      significant change 2.3+/-0.48 at baseline, down to 1.70+/-0.61 at 24 weeks. (5)
      Based on the questionnaires, the score for eating habits showed a significant
      change from the baseline 34.0+/-6.8 to 31.3+/-6.8. (6) The psychological
      assessment did not exhibit a significant difference except with scores for
      sociability, problem behavior total score and other problems. CONCLUSION: The
      leuprolide 3.75 mg (Luphere depot) is useful and safety for treating children
      with central precocious puberty.

PMID- 24904874
TI  - Changes of antithroglobulin antibody in children with congenital hypothyroidism.
AB  - PURPOSE: It has been reported that antithroglobulin (anti-TG) antibody is
      increased in the sera of both children with transient congenital hypothyroidism
      and their mothers. And transplacental transport of thyroid autoantibody was
      proposed as the pathogenesis of transient congenital hypothyroidism. However this
      is not known in nontransient congenital hypothyroidism. This study was done to
      see changes of anti-TG antibody in children with nontransient congenital
      hypothyroidism. METHODS: Study patients consisted of 60 patients diagnosed as
      congenital hypothyroidism in the Department of Pediatrics, Kyungpook National
      University Children's Hospital, Daegu, Republic of Korea between January 2010 and
      March 2013. Healthy control were 45 children showing normal thyroid function.
      Anti-TG antibody and various laboratory tests were analyzed retrospectively, and
      compared in both children with congenital hypothyroidism and controls. RESULTS:
      Anti-TG antibody was significantly higher in children with congenital
      hypothyroidism compared to healthy controls, 119.4+/-34.7 U/mL versus 80.6+/-19.6
      U/mL, respectively (P<0.001). There was no significant difference of anti-TG
      antibody in gender and age. CONCLUSION: We observed a significant increase of
      anti-TG antibody in children with nontransient congenital hypothyroidism compared
      to healthy controls. Further study focusing pathogenetic role of anti-TG antibody
      in nontransient congenital hypothyroidism is necessary. Furthermore, the clinical
      significance in the course of congenital hypothyroidism need to be known.

PMID- 24904875
TI  - Boys with precocious or early puberty: incidence of pathological brain magnetic
      resonance imaging findings and factors related to newly developed brain lesions.
AB  - PURPOSE: Brain magnetic resonance imaging (MRI) findings and factors predictive
      of pathological brain lesions in boys with precocious puberty (PP) or early
      puberty (EP) were investigated. METHODS: Sixty-one boys with PP or EP who had
      brain MRI performed were included. PP was classified into the central or
      peripheral type. Brain MRI findings were categorized into group I (pathological
      brain lesion known to cause puberty; newly diagnosed [group Ia] or previously
      diagnosed [group Ib]); group II (brain lesion possibly related to puberty); and
      group III (incidental or normal findings). Medical history, height, weight,
      hormone test results, and bone age were reviewed. RESULTS: Brain lesions in
      groups I and II were detected in 17 of 23 boys (74%) with central PP, 9 of 30
      boys (30%) with EP, and 7 of 8 boys (88%) with peripheral PP. All brain lesions
      in boys with peripheral PP were germ cell tumors (GCT), and 3 lesions developed
      later during follow-up. Group I showed earlier pubertal onset (P<0.01) and
      greater bone age advancement (P<0.05) than group III. Group III had lower birth
      weight and fewer neurological symptoms than "Ia and II" (all P<0.05). CONCLUSION:
      Earlier onset of puberty, greater bone age advancement, and/or neurological
      symptoms suggested a greater chance of pathological brain lesions in boys with
      central PP or EP. All boys with peripheral PP, even those with normal initial MRI
      findings, should be evaluated for the emergence of GCT during follow-up.

PMID- 24904876
TI  - The difference in serum alkaline phosphatase levels between girls with precocious
      puberty and those with normal puberty.
AB  - PURPOSE: Serum alkaline phosphatase (ALP) level is the most valid marker of bone
      formation. Precocious puberty (PP) in girls is characterized by early growth
      acceleration. The aim of this study was to determine whether serum ALP levels
      differ between girls with PP and those with normal puberty, and whether ALP level
      varies with age or Tanner stage. METHODS: This retrospective study included girls
      with PP (n=61) and normal puberty (n=71) who visited the outpatient clinic at
      Department of Pediatrics, Chungnam National University Hospital from March 2010
      to August 2011. We obtained age, height, parental height, weight, bone age,
      Tanner stage, and concentrations of luteinizing hormone, follicular-stimulating
      hormone, estradiol, ALP, and insulin-like growth factor-1 (IGF-1) from the
      participants' medical records. RESULTS: Age and predicted adult height were
      significantly lower in girls with PP than in those with normal puberty. The
      height standard deviation score (SDS), weight SDS, body mass index, midparental
      height, bone age, and IGF-1 level were higher in girls with PP than in those with
      normal puberty. ALP level was significantly higher in 5- to 8-year-old girls with
      PP than in age-matched girls with normal puberty. The mean ALP levels were higher
      in girls with PP than bone age-matched girls with normal puberty (P=0.0003).
      CONCLUSION: Serum ALP level showed the significance differences between girls
      with PP and those with normal puberty. The reasons for and the mechanisms
      underlying this elevation in serum ALP level in girls with PP should be
      investigated further.

PMID- 24904877
TI  - Basal luteinizing hormone and follicular stimulating hormone: is it sufficient
      for the diagnosis of precocious puberty in girls?
AB  - PURPOSE: A gonadotropin-releasing hormone stimulation test (GnRHST) is the gold
      standard in diagnosing central precocious puberty (CPP). The aim of this study
      was to investigate the diagnostic accuracy of basal gonadotropin levels for girls
      with suspected precocious puberty and to evaluate the factors affecting positive
      results of the GnRHST. METHODS: Korean girls with early pubertal development who
      visited the clinic during 2010-2012 were included. Auxological and biochemical
      tests were evaluated and a standard GnRHST was performed. A peak luteinizing
      hormone (LH) level of >=5 IU/L was considered a positive response during the
      GnRHST. RESULTS: A total of 336 girls were included. The positive responses were
      observed in 241 girls (71.7%), and negative responses were found in 95 girls
      (28.3%). In the logistic regression analysis, the coefficient of the basal LH and
      basal LH/follicular stimulating hormone (FSH) ratio was 4.23 (P<0.001) and 21.28
      (P<0.001), respectively. Receiver operating characteristic analysis showed that
      the basal LH/FSH ratio is a better predictor of the pubertal result after the
      GnRHST than the basal LH (area under the curve was 0.745 and 0.740, respectively;
      P=0.027). Among 189 girls with a basal LH of <0.1 IU/L, 105 (55.6%) had positive
      responses. CONCLUSION: An elevated level of the basal LH and basal LH/FSH ratio
      was a significant predicting factor of positive responses during the GnRHST.
      However a GnRHST was still necessary for diagnostic confirmation of CPP because
      more than half of the girls with a basal LH level below the detection limit
      revealed to have CPP.

PMID- 24904879
TI  - Serum glycated albumin as a new glycemic marker in pediatric diabetes.
AB  - PURPOSE: Serum glycated albumin (GA) has been recently used as another glycemic
      marker that reflects shorter term glycemic control than glycated hemoglobin
      (HbA1c). Insulin secretory function and glycemic fluctuation might be correlated
      with the ratio of GA to HbA1c (GA/HbA1c) in diabetic adult patients. This study
      investigated the association of GA and GA/HbA1c ratio with the levels of fasting
      C-peptide, fasting plasma glucose in type 1 and type 2 pediatric diabetes.
      METHODS: Total 50 cases from 42 patients were included. The subjects were
      classified into type 1 diabetes mellitus (T1DM) (n=30) and type 2 diabetes
      mellitus (T2DM) (n=20) group. The associations among HbA1c, GA, and GA/HbA1c
      ratio were examined. The relationship between the three glycemic indices and
      fasting glucose, fasting C-peptide were analyzed. RESULTS: Mean values of GA, the
      GA/HbA1c ratio were significantly higher in T1DM than T2DM. GA (r=0.532,
      P=0.001), HbA1c (r=0.519, P=0.002) and the GA/HbA1c ratio (r=0.409, P=0.016) were
      correlated with the fasting plasma glucose. Fasting C-peptide level arranged
      4.22+/-3.22 ng/mL in T2DM, which was significantly above the values in T1DM
      (0.26+/-0.49 ng/mL). There were no significant correlation between HbA1c and
      fasting C-peptide level. However, GA and the GA/HbA1c ratio exhibited inverse
      correlations with fasting C-peptide level (r=-0.214, P=0.002; r=-0.516, P<0.001).
      CONCLUSION: GA seems to more accurately reflects fasting plasma glucose level
      than HbA1c. GA, GA/HbA1c ratio appear to reflect insulin secretory function.

PMID- 24904878
TI  - Factors that predict a positive response on gonadotropin-releasing hormone
      stimulation test for diagnosing central precocious puberty in girls.
AB  - PURPOSE: The rapid increase in the incidence of precocious puberty in Korea has
      clinical and social significance. Gonadotropin-releasing hormone (GnRH)
      stimulation test is required to diagnose central precocious puberty (CPP),
      however this test is expensive and time-consuming. This study aimed to identify
      factors that can predict a positive response to the GnRH stimulation test.
      METHODS: Clinical and laboratory parameters, including basal serum luteinizing
      hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), were
      measured in 540 girls with clinical signs of CPP. RESULTS: Two hundred twenty
      nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L
      (the CPP group). The CPP group had advanced bone age (P<0.001), accelerated
      yearly growth rate (P<0.001), increased basal levels of LH (P=0.02), FSH
      (P<0.001), E2 (P=0.001), and insulin-like growth factor-I levels (P<0.001)
      compared to the non-CPP group. In contrast, body weight (P<0.001) and body mass
      index (P<0.001) were lower in the CPP group. Although basal LH was significantly
      elevated in the CPP group compared to the non-CPP group, there was considerable
      overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L) detected CPP
      with 87.8% sensitivity and 20.9% specificity. CONCLUSION: No single parameter can
      predict a positive response on the GnRH stimulation test with both high
      sensitivity and specificity. Therefore, multiple factors should be considered in
      evaluation of sexual precocity when deciding the timing of the GnRH stimulation
      test.

PMID- 24904880
TI  - Nongoitrous autoimmune thyroiditis with facial palsy.
AB  - We report a case of severe hypothyroidism with nongoitrous, autoimmune
      thyroiditis and pituitary hyperplasia in a 13-year-old boy, who presented with
      sudden palsy on the left side of his face. Prednisolone and antiviral medication
      was administered. However, the facial palsy did not improve completely. The
      medications were replaced with thyroxine, and the facial palsy recovered.
      Endocrinological testing showed severe hypothyroidism as follows: thyroid
      stimulating hormone (TSH) level >100 uIU/mL, T4 of 1.04 ug/dL, T3 of 0.31 ng/mL,
      and free T4 of 0.07 ng/dL. Level of serum antithyroid peroxidase antibodies was
      1,933.39 IU/mL, and that of antithyroglobulin antibodies was 848.16 IU/mL. Level
      of TSH receptor antibodies was >40 IU/L. Bioassay result for TSH receptor
      stimulating antibodies was negative. Thyroid sonography revealed no increase in
      the size or vascularity of the bilateral gland. Thyroid scintigraphy with 99mTc
      showed decreased uptake, and magnetic resonance imaging demonstrated an enlarged
      pituitary gland. 

PMID- 24904881
TI  - New take-off to an international journal.

PMID- 24904882
TI  - Current trends in glioblastoma multiforme treatment: radiation therapy and immune
      checkpoint inhibitors.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain cancer. Even with
      aggressive combination therapy, the median life expectancy for patients with GBM
      remains approximately 14 months. In order to improve the outcomes of patients
      with GBM, the development of newer treatments is critical. The concept of using
      the immune system as a therapeutic option has been suggested for several decades;
      by harnessing the body's adaptive immune mechanisms, immunotherapy could provide
      a durable and targeted treatment against cancer. However, many cancers, including
      GBM, have developed mechanisms that protect tumor cells from being recognized and
      eliminated by the immune system. For new immunotherapeutic regimens to be
      successful, overcoming immunosuppression via immune checkpoint signaling should
      be taken into consideration. 

PMID- 24904883
TI  - Molecular culprits generating brain tumor stem cells.
AB  - Despite current advances in multimodality therapies, such as surgery,
      radiotherapy, and chemotherapy, the outcome for patients with high-grade glioma
      remains fatal. Understanding how glioma cells resist various therapies may
      provide opportunities for developing new therapies. Accumulating evidence
      suggests that the main obstacle for successfully treating high-grade glioma is
      the existence of brain tumor stem cells (BTSCs), which share a number of cellular
      properties with adult stem cells, such as self-renewal and multipotent
      differentiation capabilities. Owing to their resistance to standard therapy
      coupled with their infiltrative nature, BTSCs are a primary cause of tumor
      recurrence post-therapy. Therefore, BTSCs are thought to be the main glioma cells
      representing a novel therapeutic target and should be eliminated to obtain
      successful treatment outcomes. 

PMID- 24904884
TI  - An updated nationwide epidemiology of primary brain tumors in republic of Korea.
AB  - OBJECTIVE: The aim of this report is to provide accurate nationwide epidemiologic
      data on primary brain and central nervous system (CNS) tumors in Republic of
      Korea. In 2010, we had reported first nationwide epidemiologic data on primary
      brain tumors diagnosed in 2005. In this report, we updated the data by analyzing
      primary brain and CNS tumors diagnosed in 2010 using the data from national
      cancer incidence database. METHODS: Data on primary brain and CNS tumors
      diagnosed in 2010 were collected from the Korean Central Cancer Registry. Crude
      and age-standardized rates were calculated in terms of gender, age, and
      histological type. RESULTS: A total of 10,004 patients diagnosed with primary
      brain and CNS tumors in 2010 were included in this study. Brain and CNS tumors
      occurred in females more often than in males (female to male, 1.59 : 1). The most
      common tumor was meningioma (35.5%). Pituitary tumors (18.7%), gliomas (15.1%),
      and nerve sheath tumors (10.3%) were followed in incidence. Glioblastoma
      accounted for 34.6% of all gliomas. In children (<20 years), sellar region tumors
      (pituitary and craniopharyngioma), embryonal/primitive/medulloblastoma, and germ
      cell tumors were the most common tumors. CONCLUSION: Data from this study should
      provide valuable information regarding the primary brain tumors epidemiology in
      Republic of Korea.

PMID- 24904885
TI  - Pain assessment in brain tumor patients after elective craniotomy.
AB  - OBJECTIVE: This study was performed to assess the postoperative pain of brain
      tumor patients who underwent elective craniotomy and to evaluate the factors
      associated with pain intensity. METHODS: From January 2010 to December 2011, 47
      patients with newly diagnosed brain tumors who underwent craniotomy were
      enrolled. The postoperative pain status was assessed daily until discharge using
      the visual analogue scale (VAS). RESULTS: The study participants comprised of 22
      males and 25 females with ages ranging from 18-76 years (median age, 50 years).
      Patients were divided into two groups: the painful group included patients who
      had a VAS score of more than 3 during their hospital stay after the craniotomy,
      and the tolerable group included patients who had a VAS score of 1 to 3 during
      their hospital stay. There were no differences between the two groups in terms of
      age, sex, location of surgery, history of diabetes, hypertension and smoking,
      body mass index, and hospital stay. Univariate analysis revealed that operating
      time, length of wound, head fixation, and perioperative administration of opioid
      were not associated with the intensity of postoperative pain. Daily assessment of
      VAS revealed the two peaks of pain on the operation day and the 4th postoperative
      day. The intensity of pain during the ambulation period was higher than that
      during intensive care unit (ICU) stay. CONCLUSION: Pain following elective
      craniotomy for brain tumor removal is insufficiently managed, especially after
      discharge from the ICU. More attention needs to be paid to patients' pain
      throughout the hospital stay.

PMID- 24904886
TI  - Inflamed symptomatic sellar arachnoid cyst: case report.
AB  - Sellar arachnoid cysts are rare; an infected arachnoid cyst is extremely rare as
      only one case has been reported to date in the literature. Here, we report a
      patient with an infected or inflamed sellar arachnoid cyst that was successfully
      treated with transsphenoidal surgery (TSA). A 53-year-old female with a history
      of chronic sinusitis developed a headache 5 months ago, and one month before
      admission polyuria, polydipsia, and abnormal vaginal bleeding occurred. The
      magnetic resonance imaging (MRI) showed a sellar cystic mass with a thickened
      pituitary stalk. Preoperative hormonal study revealed normal pituitary hormone
      levels except for a moderate elevation of prolactin. She was diagnosed with
      diabetes insipidus of the central nervous system origin based on a water
      deprivation test. TSA was performed under an impression of symptomatic Rathke's
      cleft cyst according to the MRI findings. Intraoperative findings showed
      confirmation of turbid intracystic contents, but micro-organisms were
      unidentified on microbial culture. Pathology of the cyst wall revealed inflamed
      meningoepithelial lining cells compatible with an arachnoid cyst. 

PMID- 24904887
TI  - Primary malignant lymphoma of the cranial vault with extra- and intracranial
      extension.
AB  - Bone involvement is a common finding in many types of lymphomas, particularly in
      advanced stages. However, cranial vault affliction has been regarded as an
      exceedingly rare presentation. Here, we report the case of a patient with cranial
      vault lymphoma who presented with a scalp mass. An 81-year-old woman presented
      with a gradually growing and non-painful frontal scalp mass that she noticed one
      month before admission. It was a flatly elevated, round mass measuring about
      6*4*4 cm. Computed tomography and magnetic resonance imaging of the brain
      revealed a contrast-enhancing intracranial extradural mass at the counter
      location of the scalp mass. The superior sagittal sinus was involved at the tumor
      site. Cerebral angiography showed that the tumor feeding vessels originated from
      the bilateral external carotid arteries. An operation was performed and the
      tumors were removed together with the involved bone. The pathologic diagnosis was
      malignant diffuse large B-cell type lymphoma. The patient was transferred to the
      Hemato-Oncology department for chemotherapy. Primary lymphoma of the cranial
      vault with scalp mass is very rare but it should be considered in the
      differential diagnosis of scalp masses. Although the results of reported cases
      are variable, the combination of surgery, radiation, and chemotherapy appears to
      offer favorable outcomes. 

PMID- 24904888
TI  - Solitary primary leptomeningeal glioma: case report.
AB  - We report a case of solitary primary leptomeningeal glioma. The mass was totally
      removed under awake surgery. Intraoperatively, no parenchymal involvement was
      noted. Histopathological study revealed a predominant anaplastic
      oligodendroglioma component and a focal anaplastic astrocytoma component, which
      was consistent with an anaplastic oligoastrocytoma. Adjuvant tomotherapy was
      followed and the tumor has not recurred until 12 months after surgery. A focal
      type of primary leptomeningeal glioma is extremely rare. We report a rare case of
      solitary primary leptomeningeal anaplastic oligoastrocytoma. 

PMID- 24904889
TI  - An intracranial chondroma with intratumoral hemorrhage: a case report and review
      of the literature.
AB  - A 55-year-old female presented to the emergency room with a complaint of aphasia.
      Her initial brain computed tomography scan showed an intracranial hemorrhage in
      the left frontal area. After surgery, histopathological examination confirmed the
      diagnosis of a chondroma. Intradural chondroma is a rare, slow growing, benign
      intracranial neoplasm, but is even rarer in combination with an intratumoral
      hemorrhage. Chondromas are generally avascular cartilaginous lesions. Our case
      was thought to be caused by the rupture of abnormally weak vessels derived from
      the friable tumor. Intradural chondromas may be included in the differential
      diagnosis of intracranial tumors with acute hemorrhages. 

PMID- 24904890
TI  - 5-aminolevulinic Acid fluorescence discriminates the histological grade of
      extraventricular neurocytoma.
AB  - Extraventricular neurocytomas are rare brain tumors that have a diverse range of
      clinical characteristics. We describe two cases involving fluorescence-guided
      resection of extraventricular neurocytoma using 5-aminolevulinic acid (5-ALA) and
      evaluate the efficacy of the technique. We found that the tumor reactions to 5
      ALA differed depending on the histologic grade. This finding shows that the 5-ALA
      fluorescence reaction may potentially be used as a biomarker of the clinical
      behavior of these tumors. To our knowledge, this is the first report in which
      fluorescence-guided resection was utilized for the resection of extraventricular
      neurocytomas. 

PMID- 24904891
TI  - A suprasellar cystic germ cell tumor initially diagnosed as an arachnoid cyst.
AB  - We report here the case of a suprasellar cystic germ cell tumor (GCT) initially
      diagnosed as an arachnoid cyst. A 10-year-old boy experienced headache,
      dizziness, and diplopia, and was shown to have an approximately 2 cm suprasellar
      cyst. Two months after endoscopic third ventriculostomy was performed, a 5-6 cm
      cystic mass with an internal enhancing component was observed in the suprasellar
      cistern. Serum human chorionic gonadotropin levels were slightly increased in the
      serum and cerebrospinal fluid (55 and 162 IU/L, respectively) but were strikingly
      elevated in the cystic fluid (14,040 IU/L). The patient showed complete
      remission, with only a very small cystic lesion remaining after surgery,
      chemotherapy, and radiation treatment for a suprasellar mixed GCT. However,
      follow-up after treatment was complicated by moyamoya syndrome and cerebral
      infarction. GCT can be considered as a rare differential diagnosis in the case of
      a suprasellar cystic mass. Evaluation of tumor markers and close follow-up will
      be necessary. 

PMID- 24904892
TI  - Pituitary symptomatic salivary gland rest cyst: case report.
AB  - Although salivary gland rest in posterior pituitary is frequently observed during
      microscopic examination at autopsy, this rest tissue rarely causes clinical
      symptoms. So far, only three symptomatic salivary gland rest cyst in pituitary
      was reported. The author reports the 4(th) case of symptomatic pituitary salivary
      gland rest cyst in 26-year-old woman presenting with severe headache. The lesion
      showed hyperdense shadow on computed tomography, high signal on T1-weighted image
      and low signal on T2-weighted image magnetic resonance imaging. There was no
      enhancement of the mass after gadolinium injection. Trans-sphenoidal approach
      revealed that the cyst wall consisted of normal appearing salivary gland and
      gelatinous cyst content. Although the pituitary salivary gland rest cyst is
      rarely symptomatic, it should be take into consideration in the differential
      diagnosis of pituitary lesions. 

PMID- 24904894
TI  - Outcome of surgical resection of symptomatic cerebral lesions in non-small cell
      lung cancer patients with multiple brain metastases.
AB  - OBJECTIVE: Patients with symptomatic brain metastases secondary to mass effect
      are often candidates for surgery. However, many of these surgical candidates are
      also found to have multiple asymptomatic tumors. This study aimed to determine
      the outcome of surgical resection of symptomatic brain metastases followed by
      chemotherapy or radiotherapy (RT) for the remnant asymptomatic lesions in non
      small cell lung cancer (NSCLC) patients with multiple brain metastases. METHODS:
      We conducted a retrospective review of the medical records of 51 NSCLC patients
      with symptomatic multiple brain metastases who underwent surgical resection, of
      whom 38 had one or more unresected asymptomatic lesions subsequently treated with
      chemotherapy and/or RT. Thirteen patients underwent resection of all metastatic
      lesions. RESULTS: Median survival for overall patient population after surgical
      resection was 10.8 months. Median survival for patients with surgical resection
      of all brain metastases was not significantly different with patients who
      underwent surgical resection of only symptomatic lesions (6.5 months vs. 10.8
      months; p=0.97). There was no statistically significant difference in survival
      according to the number of tumors (p=0.86, 0.16), or post-surgical treatment
      modalities (p=0.69). CONCLUSION: The survival time of NSCLC patients with
      multiple brain metastases after surgery for only symptomatic brain metastases is
      similar to that of patients who underwent surgery for all brain metastases. The
      remaining asymptomatic lesions may be treated with chemotherapy or radiotherapy.
      The optimal treatment modality, however, needs to be defined in prospective
      trials with larger patient cohort.

PMID- 24904893
TI  - Pyruvate dehydrogenase kinase as a potential therapeutic target for malignant
      gliomas.
AB  - Metabolic aberrations in the form of altered flux through key metabolic pathways
      are the major hallmarks of several life-threatening malignancies including
      malignant gliomas. These adaptations play an important role in the enhancement of
      the survival and proliferation of gliomas at the expense of the surrounding
      normal/healthy tissues. Recent studies in the field of neurooncology have
      directly targeted the altered metabolic pathways of malignant tumor cells for the
      development of anti-cancer drugs. Aerobic glycolysis due to elevated production
      of lactate from pyruvate regardless of oxygen availability is a common metabolic
      alteration in most malignancies. Aerobic glycolysis offers survival advantages in
      addition to generating substrates such as fatty acids, amino acids and
      nucleotides required for the rapid proliferation of cells. This review outlines
      the role of pyruvate dehydrogenase kinase (PDK) in gliomas as an inhibitor of
      pyruvate dehydrogenase that catalyzes the oxidative decarboxylation of pyruvate.
      An in-depth investigation on the key metabolic enzyme PDK may provide a novel
      therapeutic approach for the treatment of malignant gliomas. 

PMID- 24904895
TI  - Bromocriptine therapy for the treatment of invasive prolactinoma: the single
      institute experience.
AB  - OBJECTIVE: The objective of this study was to describe and characterize the
      clinical course of treatment for invasive prolactinoma patients using
      bromocriptine. METHODS: The study group included 23 patients who were treated
      with bromocriptine for their invasive prolactinomas. Clinical histories, serum
      prolactin level and pituitary hormone assessments, tumor diameter and signal
      intensity on sella magnetic resonance imaging (MRI), visual field exams and the
      dosage of medications were reviewed for each patient. RESULTS: During 30 months
      (median, range 6-99) of follow-up period, 19 patients treated with bromocriptine
      alone achieved biochemical remission. Four patients changed the medication to
      cabergoline due to the adverse effects or observed resistance of bromocriptine
      treatment. All of five patients who had visual symptoms improved after the course
      of medication. Four surgically treated patients were not able to discontinue
      medication because they could not maintain biochemical remission state without
      medication. Multivariate analysis showed that decreased enhancement on the
      initial followed MRI after medication and longer follow-up periods were
      associated with higher radiologic response. CONCLUSION: We reassure that the
      dopamine agonist is safe and effective for the treatment of invasive pituitary
      adenomas. Meanwhile, surgery has a limited role on biochemical remission.
      Decreased enhancement on the initial follow-up MRI after medication may reflect
      the treatment response. Further study is required to validate the role of MRI or
      other factors on the actual prognosis.

PMID- 24904896
TI  - Treatment Options of Metastatic Brain Tumors from Hepatocellular Carcinoma:
      Surgical Resection vs. Gamma Knife Radiosurgery vs. Whole Brain Radiation
      Therapy.
AB  - OBJECTIVE: Although metastasis of hepatocellular carcinoma to the brain is
      uncommon, it is associated with a very high mortality rate and most patients
      usually expire within 1 year after brain metastasis. The aim of this study is to
      identify the effectiveness of the active interventions such as gamma knife
      radiosurgery or surgical intervention for these patients. METHODS: We
      retrospectively reviewed the medical records and imaging data of 59 patients with
      metastatic brain tumors from hepatocellular carcinoma from May 2004 to September
      2012. The study included patients with available clinical and radiological data
      who had been diagnosed with metastatic hepatocellular carcinoma of the brain,
      confirmed by magnetic resonance imaging. The overall survival time was analyzed
      and compared according to each risk factor. RESULTS: The mean age at diagnosis of
      metastatic brain tumor was 52.2 years (14-77). The mean follow-up duration was
      13.3 weeks (0.1-117.6). Overall median survival was 4.3 weeks (95% confidence
      interval, 2.2-6.4). The results from an analysis of clinical factors related to
      survival revealed that treatment modalities were significantly related to the
      patient's survival (log rank, p=0.006). Twenty patients (32.8%) experienced tumor
      bleeding, and the survival time of the patients with tumor bleeding tended to be
      shorter, although the result was not statistically significant (log rank,
      p=0.058). Hepatic reserve, by Child-Pugh classification, was grade A in 38
      patients (64.4%), grade B in 16 patients (27.1%), and grade C in 5 patients
      (8.5%), and was significantly related to the patient's survival (log rank,
      p=0.000). CONCLUSION: Although patients with metastatic brain tumors from
      hepatocellular carcinoma showed poor survival, active intervention including
      surgical resection or gamma knife radiosurgery may result in better survival,
      especially if patients have preserved liver function.

PMID- 24904897
TI  - Long term clinical outcomes of malignant meningiomas.
AB  - OBJECTIVE: Malignant meningiomas are rare and have worse prognosis than benign
      meningiomas. We report our experience of a malignant meningioma and review
      relevant literature in an attempt to investigate the clinical features,
      treatment, and prognosis of these tumors. METHODS: Fifteen patients underwent
      surgical treatment for intracranial malignant meningiomas between year 1990 and
      2012 in our institution. Anaplastic meningiomas were diagnosed in thirteen cases
      and papillary meningiomas in two. Fourteen patients (93.3%) received radiotherapy
      after surgical resection. All patients were followed regularly including clinical
      neurological follow-up as well as magnetic resonance imaging. Progression was
      determined radiographically when there was more than 10% of mass volume increase
      or when there were onset or worsening of neurological symptoms not attributable
      to other causes. RESULTS: Six patients were male and nine were women, and their
      mean age was 56.9 years (range 36-78). The median follow-up was 54 months (range
      3-246). According to our study result, the 5-year progression free survival rate
      of malignant meningiomas was 53.6%. There were 2 cases (13.3%) of postoperative
      complications. Recurrences were confirmed in 4 patients (26.7%) during follow-up,
      the median recurrence time was 35 months (range 12-61), and further procedures
      were performed. Two of the recurred patients were treated with radiosurgery after
      secondary tumor resection, and other two patients were treated with radiosurgery
      alone. There was no more recurred disease patients in the follow-up period after
      then. CONCLUSION: We report the outcomes of the aggressive surgery with radiation
      of malignant meningiomas. Although the data is limited, we found that
      radiosurgery treatment had favorable tumor control on recurred patients from our
      experience.

PMID- 24904898
TI  - Primary intracranial fibrosarcoma presenting with hemorrhage.
AB  - Primary intracranial fibrosarcomas (PIFs) are extremely rare and the origin of
      these tumors is still controversial. The rarity of primary intracranial
      fibrosarcomas makes it difficult to diagnose them correctly and establish a
      standard treatment. The pathologic diagnosis is made by distinguishing findings
      from light microscopic and immunohistochemistry analysis. PIFs have been known to
      be very aggressive neoplasms. The extra-axial location of the tumor could provide
      an opportunity to perform a total resection even if it does not mean a cure. We
      present a case of PIFs mimicking a falx meningioma in a 17-year-old man. 

PMID- 24904899
TI  - Hemangiopericytoma of the posterior fossa: a case report and review of the
      literature.
AB  - Intracranial hemangiopericytoma is unusual, and those occurring in the posterior
      fossa is extremely rare; we report such a rare case of hemangiopericytoma of the
      posterior fossa. The radiologic findings and gross characteristics of
      hemangiopericytomas are sometimes quite similar to those of meningiomas. Although
      extremely rare, the operator should be aware of the existence of this disorder to
      dexterously manage the aggressive nature and high vascular tendency of
      hemangiopericytomas. The radiological features and histological findings in this
      case are discussed in this study. 

PMID- 24904900
TI  - Extremely delayed brain metastasis from renal cell carcinoma.
AB  - Brain metastasis occurs in 3.9-24% of patients with renal cell carcinoma (RCC),
      with an average interval from nephrectomy to brain metastasis of 1 to 3 years. A
      few cases have been reported where brain metastasis occurred after a delay of
      more than 10 years from the initial onset of renal cell carcinoma. This long
      interval for central nervous system metastasis from the primary cancer has been
      recognized as an indicator of better prognosis. Histopathological confirmation
      and aggressive treatment must be considered in these delayed brain metastases
      cases, since the patients usually show long survival and good prognosis. We
      present a case of a 76-year-old woman who developed extremely late multiple brain
      metastases 18 years after a nephrectomy for RCC. 

PMID- 24904901
TI  - A case of multiple myeloma with brain parenchyme involvement.
AB  - Multiple myelomas (MM) are characterized by monoclonal proliferation of
      immunoglobulin (Ig)-secreting plasma cells. Central nervous system involvement is
      a rare complication of MM, and it can present as either an intraparenchymal or a
      leptomeningeal lesion. A 77-year-old woman was transferred from the dementia
      clinic in July 2012. She had a large heterogeneous signal mass with central
      necrosis and with pial involvement in the left frontal lobe with destruction of
      the frontal bone that was observed on computed tomography and magnetic resonance
      imaging. Multiple punched out radiolucent lesions were also noted on the skull X
      ray. Serum protein electrophoresis revealed an IgA-kappa monoclonal gammopathy.
      External lumbar drainage was helpful for treating the fluid collection underneath
      the scalp after an orbitozygomatic craniotomy with duroplasty. 

PMID- 24904902
TI  - Fulminant meningitis after radiotherapy for clival chordoma.
AB  - The best treatment for clival chordoma is obtained with total surgical excision,
      sometimes combined with adjuvant radiotherapy. A cerebrospinal fluid (CSF)
      fistula is a fatal complication that may occur following extended transsphenoidal
      surgery (TSS) and adjuvant radiotherapy. We report a case of fulminant meningitis
      without a CSF fistula in a 57-year-old woman who underwent TSS and multiple
      radiotherapies for a clival chordoma. She presented to our emergency room with
      copious epistaxis and odor inside her nasal cavity and had an unexpected fatal
      outcome. She was diagnosed with meningitis based on CSF culture and blood
      culture. While treating clival chordomas with adjuvant radiotherapy, clinicians
      should be aware of the possibility of fulminant meningitis. 

PMID- 24904903
TI  - Pituitary apoplexy mimicking meningitis.
AB  - Pituitary apoplexy is a rare but life-threatening disorder. Clinical presentation
      of this condition includes severe headaches, impaired consciousness, fever,
      visual disturbance, and variable ocular paresis. The clinical presentation of
      meningeal irritation is very rare. Nonetheless, if present and associated with
      fever, pituitary apoplexy may be misdiagnosed as a meningitis. We experienced a
      case of pituitary apoplexy masquerading as a meningitis. A 42-year-old man
      presented with meningitis associated symptoms and initial imaging studies did not
      show evidence of intra-lesional hemorrhage in the pituitary mass. However, a
      follow-up imaging after neurological deterioration revealed pituitary apoplexy.
      Hereby, we report our case with a review of literatures. 

PMID- 24904904
TI  - Primary spinal cord melanoma in thoracic spine with leptomeningeal dissemination
      and presenting hydrocephalus.
AB  - Primary spinal cord melanoma is a rare central nervous system malignant tumor.
      Usually it resembles an intradural extramedullary (IDEM) nerve sheath tumor or
      melanoma. We experienced a patient with upper thoracic primary IDEM spinal cord
      melanoma who was diagnosed to be with hydrocephalus and without intracranial
      lesions. Initial symptoms of the patient were related to the hydrocephalus and
      the primary spinal cord melanoma was diagnosed eight months later. At the first
      operation, complete resection was impossible and the patient refused additional
      radiotherapy or chemotherapy. At 22 months after surgery, the patient revisited
      our institution with recurrent both leg weakness. Leptomeningeal dissemination
      was present in the whole spinal cord and only partial resection of tumor was
      performed. The symptoms slightly improved after surgery. Primary spinal cord
      melanoma is extremely rare but complete resection and additional radiotherapy or
      chemotherapy can prolong the disease free interval. Hydrocephalus or signs of
      increased intracranial pressure may be the diagnostic clue of spinal cord
      malignancy and progression. 

PMID- 24904905
TI  - An ependymal cyst in cerebello-pontine angle presenting with syncope.
AB  - Intracranial ependymal cysts are rare, congenital, benign lesions. These commonly
      occur in the supratentorial regions and usually generate no symptoms. The
      cerebellopontine angle (CPA) is an extremely rare site for ependymal cysts.
      Furthermore, there are no previous reports of CPA ependymal cysts related to
      syncope. We report a case of ependymal cyst in the left CPA with syncope. The
      patient underwent a cardiologic evaluation for syncope after admission, but there
      were no definite cardiologic abnormal findings. He underwent fenestration into
      the subarachnoid space, and the pathologic diagnosis revealed an ependymal cyst.
      We analyzed this case with review of other literatures. 

PMID- 24904906
TI  - Potential contribution of type I alveolar epithelial cells to chronic neonatal
      lung disease.
AB  - The alveolar surface is covered by large flat Type I cells (alveolar epithelial
      cells 1, AEC1). The normal physiological function of AEC1s involves gas exchange,
      based on their location in approximation to the capillary endothelium and their
      thinness, and in ion and water flux, as shown by the presence of solute active
      transport proteins, water channels, and impermeable tight junctions between
      cells. With the recent ability to produce relatively pure cultures of AEC1 cells,
      new functions have been described. These may be relevant to lung injury, repair,
      and the abnormal development that characterizes bronchopulmonary dysplasia (BPD).
      To hypothesize a potential role for AEC1 in the development of lung injury and
      abnormal repair/development in premature lungs, evidence is presented for their
      presence in the developing lung, how their source may not be the Type II cell
      (AEC2) as has been assumed for 40 years, and how the cell can be damaged by same
      type of stressors as those which lead to BPD. Recent work shows that the cells
      are part of the innate immune response, capable of producing pro-inflammatory
      mediators, which could contribute to the increase in inflammation seen in early
      BPD. One of the receptors found exclusively on AEC1 cells in the lung, called
      RAGE, may also have a role in increased inflammation and alveolar simplification.
      While the current evidence for AEC1 involvement in BPD is circumstantial and
      limited at present, the accumulating data supports several hypotheses and
      questions regarding potential differences in the behavior of AEC1 cells from
      newborn and premature lung compared with the adult lung. 

PMID- 24904907
TI  - Moderate Alcohol Exposure during the Rat Equivalent to the Third Trimester of
      Human Pregnancy Alters Regulation of GABAA Receptor-Mediated Synaptic
      Transmission by Dopamine in the Basolateral Amygdala.
AB  - Fetal ethanol (EtOH) exposure leads to a range of neurobehavioral alterations,
      including deficits in emotional processing. The basolateral amygdala (BLA) plays
      a critical role in modulating emotional processing, in part, via dopamine (DA)
      regulation of GABA transmission. This BLA modulatory system is acquired during
      the first 2 weeks of postnatal life in rodents (equivalent to the third trimester
      of human pregnancy) and we hypothesized that it could be altered by EtOH exposure
      during this period. We found that exposure of rats to moderate levels of EtOH
      vapor during the third trimester-equivalent [postnatal days (P) 2-12] alters DA
      modulation of GABAergic transmission in BLA pyramidal neurons during
      periadolescence. Specifically, D1R-mediated potentiation of spontaneous
      inhibitory postsynaptic currents (IPSCs) was significantly attenuated in EtOH
      exposed animals. However, this was associated with a compensatory decrease in D3R
      mediated suppression of miniature IPSCs. Western blot analysis revealed that
      these effects were not a result of altered D1R or D3R levels. BLA samples from
      EtOH-exposed animals also had significantly lower levels of the DA precursor (L
      3,4-dihydroxyphenylalanine) but DA levels were not affected. This is likely a
      consequence of reduced catabolism of DA, as indicated by reduced levels of 3,4
      dihydroxyphenylacetic acid and homovanillic acid in the BLA samples. Anxiety-like
      behavior was not altered in EtOH-exposed animals. This is the first study to
      demonstrate that the modulatory actions of DA in the BLA are altered by
      developmental EtOH exposure. Although compensatory adaptations were engaged in
      our moderate EtOH exposure paradigm, it is possible that these are not able to
      restore homeostasis and correct anxiety-like behaviors under conditions of
      heavier EtOH exposure. Therefore, future studies should investigate the potential
      role of alterations in the modulatory actions of DA in the pathophysiology of
      fetal alcohol spectrum disorders. 

PMID- 24904908
TI  - Use of emerging technologies to assess differences in outdoor physical activity
      in st. Louis, missouri.
AB  - INTRODUCTION: Abundant evidence shows that regular physical activity (PA) is an
      effective strategy for preventing obesity in people of diverse socioeconomic
      status (SES) and racial groups. The proportion of PA performed in parks and how
      this differs by proximate neighborhood SES has not been thoroughly investigated.
      The present project analyzes online public web data feeds to assess differences
      in outdoor PA by neighborhood SES in St. Louis, MO, USA. METHODS: First, running
      and walking routes submitted by users of the website MapMyRun.com were
      downloaded. The website enables participants to plan, map, record, and share
      their exercise routes and outdoor activities like runs, walks, and hikes in an
      online database. Next, the routes were visually illustrated using geographic
      information systems. Thereafter, using park data and 2010 Missouri census poverty
      data, the odds of running and walking routes traversing a low-SES neighborhood,
      and traversing a park in a low-SES neighborhood were examined in comparison to
      the odds of routes traversing higher-SES neighborhoods and higher-SES parks.
      RESULTS: RESULTS show that a majority of running and walking routes occur in or
      at least traverse through a park. However, this finding does not hold when
      comparing low-SES neighborhoods to higher-SES neighborhoods in St. Louis. The
      odds of running in a park in a low-SES neighborhood were 54% lower than running
      in a park in a higher-SES neighborhood (OR = 0.46, CI = 0.17-1.23). The odds of
      walking in a park in a low-SES neighborhood were 17% lower than walking in a park
      in a higher-SES neighborhood (OR = 0.83, CI = 0.26-2.61). CONCLUSION: The novel
      methods of this study include the use of inexpensive, unobtrusive, and publicly
      available web data feeds to examine PA in parks and differences by neighborhood
      SES. Emerging technologies like MapMyRun.com present significant advantages to
      enhance tracking of user-defined PA across large geographic and temporal
      settings.

PMID- 24904910
TI  - Mental health research in the Syrian humanitarian crisis.

PMID- 24904909
TI  - Development and implementation of a smartphone application to promote physical
      activity and reduce screen-time in adolescent boys.
AB  - PURPOSE: To describe the development and implementation of a smartphone
      application (app) designed to promote physical activity and reduce screen-time in
      adolescent boys considered "at-risk" of obesity. METHODS: An app was developed to
      support the delivery of a face-to-face school-based obesity prevention program
      known as the "Active Teen Leaders Avoiding Screen-time" (ATLAS) program. ATLAS
      was guided by self-determination theory and social cognitive theory and evaluated
      using a cluster randomized controlled trial with 361 boys (12.7 +/- 0.5 years) in
      14 secondary schools. Following the completion of the study, participants in the
      intervention group completed a process evaluation questionnaire and focus groups
      were conducted with 42 students to explore their general perceptions of the ATLAS
      program and their experience with the smartphone app. Barriers and challenges
      encountered in the development, implementation, and evaluation of the app are
      also described. RESULTS: Participation in the study was not contingent on
      ownership of a smartphone, but 70% of participants in the intervention group
      reported having access to a smartphone or tablet device. Focus group participants
      reported an enjoyment of the program, and felt that it had provided them with new
      skills, techniques, and routines for the future. However, their engagement with
      the smartphone app was limited, due to a variety of reasons. Barriers to the
      implementation and evaluation of the app included limited access to smartphone
      devices, technical problems with the push notifications, lack of access to usage
      data, and the challenges of maintaining participants' interest in using the app.
      CONCLUSION: Although participants reported high levels of satisfaction with the
      ATLAS program in general, the smartphone app was not used extensively. Additional
      strategies and features may be needed to enhance engagement in adolescent boys.

PMID- 24904911
TI  - The Effects of Storage Temperature on the Growth of Vibrio parahaemolyticus and
      Organoleptic Properties in Oysters.
AB  - During harvesting and storage, microbial pathogens and natural spoilage flora may
      grow, negatively affecting the composition and texture of oysters and posing a
      potential health threat to susceptible consumers. A solution to these problems
      would mitigate associated damaging effects on the seafood industry. The purpose
      of this study was to investigate the effects of storage temperature on growth of
      vibrios as well as other microbial, sensory, and textural characteristics of post
      harvest shellstock Eastern oysters (Crassostrea virginica). Oysters harvested
      from the Chesapeake Bay, Maryland, during summer months (June, July, and August,
      2010) were subjected to three storage temperatures (5, 10, and 20 degrees C) over
      a 10-day period. At selected time intervals (0, 1, 3, 7, and 10 days), two
      separate samples of six oysters each were homogenated and analyzed for pH,
      halophilic plate counts (HPC), total vibrios, and Vibrio parahaemolyticus (Vp).
      Oyster meats shucked after storage were also organoleptically evaluated
      (acceptability, appearance, and odor). Texture analysis was performed using a
      texture analyzer on meats shucked from oysters held under the same conditions.
      The pH of the oyster homogenates showed no consistent pattern with storage time
      and temperature. The HPC (4.5-9.4 log CFU/g) were highest on day 7 at 20 degrees
      C while olfactory acceptance reduced with time and increasing storage
      temperatures. The Vp counts increased over time from 3.5 to 7.5 log MPN/g by day
      10. Loss of freshness as judged by appearance and odor was significant over time
      (p < 0.05). Toughness of oysters increased with storage time at 5 and 10 degrees
      C from days 1 to 3 but was inconsistent after day 7. The results indicate that
      the length of storage and temperature had a significant effect on bacterial
      counts and olfactory acceptance of oysters but had an inconsistent effect on
      texture. 

PMID- 24904913
TI  - The European Masters Degree in Disaster Medicine (EMDM): A Decade of Exposure.

PMID- 24904914
TI  - The grand challenge: use of a new approach in developing policies in the area of
      radiation and health.

PMID- 24904912
TI  - Estimating the potential annual welfare impact of innovative drugs in use in
      Switzerland.
AB  - Expenditures of health care systems are increasing from year to year. Therefore,
      this study aimed to estimate the difference in costs and benefits of innovative
      pharmaceuticals launched 2000 onward compared to standard treatment on the
      national economy of Switzerland in 2010. The approach and formula described in
      the pilot study by Tsiachristas et al. (1), which analyzed the situation of
      welfare effects in the Netherlands, served as a model for our own calculations. A
      literature search was performed to identify cost-utility or cost-effectiveness
      studies of drugs launched 2000 onward compared to standard treatment. All
      parameters required for the calculation of welfare effects were derived from
      these analyses. The base-case threshold value of a quality-adjusted life year was
      set to CHF 100,000. Overall, 31 drugs were included in the welfare calculations.
      The introduction of innovative pharmaceuticals since 2000 onward to the Swiss
      market led to a potential welfare gain of about CHF 781 million in the year 2010.
      Univariate sensitivity analysis showed that results were robust. Probably because
      of the higher benefits of new drugs on health and quality of life compared to
      standard treatment, these drugs are worth the higher costs. The literature search
      revealed that there is a lack of information about the effects of innovative
      pharmaceuticals on the overall economy of Switzerland. Our study showed that
      potential welfare gains in 2010 by introducing innovative pharmaceuticals to the
      Swiss market were substantial. Considering costs and benefits of new drugs is
      important. 

PMID- 24904915
TI  - Help-seeking in people with exceptional experiences: results from a general
      population sample.
AB  - BACKGROUND: Exceptional experiences (EE) are experiences that deviate from
      ordinary experiences, for example precognition, supernatural appearances, or deja
      vues. In spite of the high frequency of EE in the general population, little is
      known about their effect on mental health and about the way people cope with EE.
      This study aimed to assess the quality and quantity of EE in persons from the
      Swiss general population, to identify the predictors of their help-seeking, and
      to determine how many of them approach the mental health system. METHODS: An on
      line survey was used to evaluate a quota sample of 1580 persons representing the
      Swiss general population with respect to gender, age, and level of education.
      Multinomial logistic regression was applied to integrate help-seeking, self
      reported mental disorder, and other variables in a statistical model designed to
      identify predictors of help-seeking in persons with EE. RESULTS: Almost all
      participants (91%) experienced at least one EE. Generally, help-seeking was more
      frequent when the EE were of negative valence. Help-seeking because of EE was
      less frequent in persons without a self-reported mental disorder (8.6%) than in
      persons with a disorder (35.1%) (OR = 5.7). Even when frequency and attributes of
      EE were controlled for, people without a disorder sought four times less often
      help because of EE than expected. Persons with a self-reported diagnosis of
      mental disorder preferred seeing a mental health professional. Multinomial
      regression revealed a preference for healers in women with less education, who
      described themselves as believing and also having had more impressive EE.
      CONCLUSION: Persons with EE who do not indicate a mental disorder less often
      sought help because of EE than persons who indicated a mental disorder. We
      attribute this imbalance to a high inhibition threshold to seek professional
      help. Moreover, especially less educated women did not approach the mental health
      care system as often as other persons with EE, but preferred seeing a healer.

PMID- 24904916
TI  - The built environment predicts observed physical activity.
AB  - BACKGROUND: In order to improve our understanding of the relationship between the
      built environment and physical activity, it is important to identify associations
      between specific geographic characteristics and physical activity behaviors.
      PURPOSE: Examine relationships between observed physical activity behavior and
      measures of the built environment collected on 291 street segments in
      Indianapolis and St. Louis. METHODS: Street segments were selected using a
      stratified geographic sampling design to ensure representation of neighborhoods
      with different land use and socioeconomic characteristics. Characteristics of the
      built environment on-street segments were audited using two methods: in-person
      field audits and audits based on interpretation of Google Street View imagery
      with each method blinded to results from the other. Segments were dichotomized as
      having a particular characteristic (e.g., sidewalk present or not) based on the
      two auditing methods separately. Counts of individuals engaged in different forms
      of physical activity on each segment were assessed using direct observation. Non
      parametric statistics were used to compare counts of physically active
      individuals on each segment with built environment characteristic. RESULTS:
      Counts of individuals engaged in physical activity were significantly higher on
      segments with mixed land use or all non-residential land use, and on segments
      with pedestrian infrastructure (e.g., crosswalks and sidewalks) and public
      transit. CONCLUSION: Several micro-level built environment characteristics were
      associated with physical activity. These data provide support for theories that
      suggest changing the built environment and related policies may encourage more
      physical activity.

PMID- 24904917
TI  - Problems and future approaches for assessment of periodontal disease.

PMID- 24904918
TI  - The HEART Mobile Phone Trial: The Partial Mediating Effects of Self-Efficacy on
      Physical Activity among Cardiac Patients.
AB  - BACKGROUND: The ubiquitous use of mobile phones provides an ideal opportunity to
      deliver interventions to increase physical activity levels. Understanding
      potential mediators of such interventions is needed to increase their
      effectiveness. A recent randomized controlled trial of a mobile phone and
      Internet (mHealth) intervention was conducted in New Zealand to determine the
      effectiveness on exercise capacity and physical activity levels in addition to
      current cardiac rehabilitation (CR) services for people (n = 171) with ischemic
      heart disease. Significant intervention effect was observed for self-reported
      leisure-time physical activity and walking, but not peak oxygen uptake at 24
      weeks. There was also significant improvement in self-efficacy. OBJECTIVE: To
      evaluate the mediating effect of self-efficacy on physical activity levels in an
      mHealth delivered exercise CR program. METHODS: Treatment evaluations were
      performed on the principle of intention to treat. Adjusted regression analyses
      were conducted to evaluate the main treatment effect on leisure-time physical
      activity and walking at 24 weeks, with and without change in self-efficacy as the
      mediator of interest. RESULTS: Change in self-efficacy at 24 weeks significantly
      mediated the treatment effect on leisure-time physical activity by 13%, but only
      partially mediated the effect on walking by 4% at 24 weeks. CONCLUSION: An
      mHealth intervention involving text messaging and Internet support had a positive
      treatment effect on leisure-time physical activity and walking at 24 weeks, and
      this effect was likely mediated through changes in self-efficacy. Future trials
      should examine other potential mediators related to this type of intervention.

PMID- 24904920
TI  - New insight into rheology and flow properties of complex fluids with Doppler
      optical coherence tomography.
AB  - Flow properties of complex fluids such as colloidal suspensions, polymer
      solutions, fiber suspensions and blood have a vital function in many
      technological applications and biological systems. Yet, the basic knowledge on
      their properties is inadequate for many practical purposes. One important reason
      for this has been the lack of effective experimental methods that would allow
      detailed study of the flow behavior of especially opaque multi-phase fluids.
      Optical Coherence Tomography (OCT) is an emerging technique capable of
      simultaneous measurement of the internal structure and motion of most opaque
      materials, with resolution in the micrometer scale and measurement frequency up
      to 100 kHz. This mini-review will examine the recent results on the use of
      Doppler-OCT in the context of flows and rheological properties of complex fluids
      outside biomedical field. 

PMID- 24904919
TI  - Jump In! An Investigation of School Physical Activity Climate, and a Pilot Study
      Assessing the Acceptability and Feasibility of a Novel Tool to Increase Activity
      during Learning.
AB  - Physical activity (PA) benefits children's physical and mental health and
      enhances academic performance. However, in many nations, PA time in school is
      decreasing under competing pressures for time during the school day. The present
      paper argues that PA should not be reduced or seen as incompatible with academic
      learning. Instead, the authors contend that it is critical to develop tools that
      incorporate PA into content learning during the school day. To facilitate the
      development of such tools, the authors conducted 6 focus group discussions with
      12 primary school teachers and administrators to better understand the school
      climate around PA as well as school readiness to embrace PA tools that can be
      used during academic content learning. In addition, a pilot test of a new health
      promotion tool, the Jump In! educational response mat, was conducted with 21
      second-grade students from one classroom in Northern Colorado in 2013. The
      results of both studies demonstrated acceptability and feasibility of
      incorporating PA into classroom learning, and suggested that tools like Jump In!
      may be effective at overcoming many of the PA barriers at schools. Teachers and
      administrators valued PA, believed that students were not getting enough PA, and
      were receptive to the idea of incorporating PA into classroom learning. Students
      who used Jump In! mats during a math lesson reported more interest in the class
      material and rated themselves as more alert during the lesson, compared to
      students who did not use the response mats. In addition, incorporating PA into
      the lesson did not impair performance on a quiz that assessed learning of the
      math content. Jump In! mats were successfully integrated into the lesson plan and
      were well-received by teachers and students. Together, the results of these
      studies suggest that, given the right tools, incorporating more PA into classroom
      learning may be beneficial and well-received by students, teachers, and
      administrators. 

PMID- 24904921
TI  - Realizing serine/threonine ligation: scope and limitations and mechanistic
      implication thereof.
AB  - Serine/Threonine ligation (STL) has emerged as an alternative tool for protein
      chemical synthesis, bioconjugations as well as macrocyclization of peptides of
      various sizes. Owning to the high abundance of Ser/Thr residues in natural
      peptides and proteins, STL is expected to find a wide range of applications in
      chemical biology research. Herein, we have fully investigated the compatibility
      of the STL strategy for X-Ser/Thr ligation sites, where X is any of the 20
      naturally occurring amino acids. Our studies have shown that 17 amino acids are
      suitable for ligation, while Asp, Glu, and Lys are not compatible. Among the
      working 17 C-terminal amino acids, the retarded reaction resulted from the bulky
      beta-branched amino acid (Thr, Val, and Ile) is not seen under the current
      ligation condition. We have also investigated the chemoselectivity involving the
      amino group of the internal lysine which may compete with the N-terminal Ser/Thr
      for reaction with the C-terminal salicylaldehyde (SAL) ester aldehyde group. The
      result suggested that the free internal amino group does not adversely slow down
      the ligation rate. 

PMID- 24904923
TI  - Paroxysmal sympathetic hyperactivity in hemispheric intraparenchymal hemorrhage.
AB  - INTRODUCTION: Paroxysmal sympathetic hyperactivity (PSH) is a hyperadrenergic
      syndrome that may follow acute brain injury characterized by episodic,
      hyperadrenergic alterations in vital signs. Identifying commonality in lesion
      localization in patients with PSH is challenging, but intraparenchymal hemorrhage
      (IPH) represents a focal injury that might provide insight. We describe a series
      of patients with IPH that developed PSH, and review the literature. METHODS:
      Patients with IPH who developed PSH were identified from OHSU hospital records. A
      literature review was conducted to identify similar cases through PUBMED, OVID,
      and Google Scholar. RESULTS: Three cases meeting criteria for PSH were
      identified. Hemorrhage volume ranged from 70 to 128 mL, and intracranial
      hemorrhage score ranged from 2 to 3. The laterality of the hemorrhage and
      significant volume of hemorrhage was similar in each of the patients,
      specifically all hemorrhages were large, subcortical, and right-sided. A
      literature search identified six additional cases, half of whom reported a right
      hemisphere hemorrhage and the majority also had subcortical localization.
      CONCLUSIONS: Our literature review identified six cases of IPH associated with
      PSH with five cases having subcortical lesion locations, echoing the areas of
      disruption in our three cases. On the basis of these observations, we hypothesize
      that injuries along the pathway from the insular cortex to downstream sympathetic
      centers may remove tonic inhibition leading to unchecked sympathetic outflow.
      Prospective investigations of lesion location in patients with IPH and PSH are
      warranted to test this hypothesis, especially with advanced neuroimaging
      techniques.

PMID- 24904922
TI  - RGD-conjugated rod-like viral nanoparticles on 2D scaffold improve bone
      differentiation of mesenchymal stem cells.
AB  - Viral nanoparticles have uniform and well-defined nano-structures and can be
      produced in large quantities. Several plant viral nanoparticles have been tested
      in biomedical applications due to the lack of mammalian cell infectivity. We are
      particularly interested in using Tobacco mosaic virus (TMV), which has been
      demonstrated to enhance bone tissue regeneration, as a tunable nanoscale building
      block for biomaterials development. Unmodified TMV particles have been shown to
      accelerate osteogenic differentiation of adult stem cells by synergistically
      upregulating bone morphogenetic protein 2 (BMP2) and integrin-binding bone
      sialoprotein (IBSP) expression with dexamethasone. However, their lack of
      affinity to mammalian cell surface resulted in low initial cell adhesion. In this
      study, to increase cell binding capacity of TMV based material the chemical
      functionalization of TMV with arginine-glycine-aspartic acid (RGD) peptide was
      explored. An azide-derivatized RGD peptide was "clicked" to tyrosine residues on
      TMV outer surface via an efficient copper(I) catalyzed azide-alkyne cycloaddition
      (CuAAC) reaction. The ligand spacing is calculated to be 2-4 nm, which could
      offer a polyvalent ligand clustering effect for enhanced cell receptor signaling,
      further promoting the proliferation and osteogenic differentiation of bone marrow
      derived mesenchymal stem cells (BMSCs). 

PMID- 24904924
TI  - Diffeomorphometry and geodesic positioning systems for human anatomy.
AB  - The Computational Anatomy project has largely been a study of large deformations
      within a Riemannian framework as an efficient point of view for generating
      metrics between anatomical configurations. This approach turns D'Arcy Thompson's
      comparative morphology of human biological shape and form into a metrizable
      space. Since the metric is constructed based on the geodesic length of the flows
      of diffeomorphisms connecting the forms, we call it diffeomorphometry. Just as
      importantly, since the flows describe algebraic group action on anatomical
      submanifolds and associated functional measurements, they become the basis for
      positioning information, which we term geodesic positioning. As well the geodesic
      connections provide Riemannian coordinates for locating forms in the anatomical
      orbit, which we call geodesic coordinates. These three components taken together 
      the metric, geodesic positioning of information, and geodesic coordinates - we
      term the geodesic positioning system. We illustrate via several examples in human
      and biological coordinate systems and machine learning of the statistical
      representation of shape and form.

PMID- 24904925
TI  - Aphasia: Current Concepts in Theory and Practice.
AB  - Recent advances in neuroimaging contribute to a new insights regarding brain
      behavior relationships and expand understanding of the functional neuroanatomy of
      language. Modern concepts of the functional neuroanatomy of language invoke rich
      and complex models of language comprehension and expression, such as dual stream
      networks. Increasingly, aphasia is seen as a disruption of cognitive processes
      underlying language. Rehabilitation of aphasia incorporates evidence based and
      person-centered approaches. Novel techniques, such as methods of delivering
      cortical brain stimulation to modulate cortical excitability, such as repetitive
      transcranial magnetic stimulation and transcranial direct current stimulation,
      are just beginning to be explored. In this review, we discuss the historical
      context of the foundations of neuroscientific approaches to language. We sample
      the emergent theoretical models of the neural substrates of language and
      cognitive processes underlying aphasia that contribute to more refined and
      nuanced concepts of language. Current concepts of aphasia rehabilitation are
      reviewed, including the promising role of cortical stimulation as an adjunct to
      behavioral therapy and changes in therapeutic approaches based on principles of
      neuroplasticity and evidence-based/person-centered practice to optimize
      functional outcomes.

PMID- 24904926
TI  - The influence of elastin degradation products, glucose and atorvastatin on
      metalloproteinase-1, -2, -9 and tissue inhibitor of metalloproteinases-1, -2, -3
      expression in human retinal pigment epithelial cells.
AB  - PURPOSE: Hyperglycemia and increased concentrations of elastin degradation
      products (EDPs) are common findings in patients with diabetes, atherosclerosis
      and hypertension. The aim of this study was to assess the influence of high
      glucose, EDPs and atorvastatin on MMP-1, MMP-2, MMP-9 and TIMP1-3 gene expression
      in human retinal pigment epithelial cells (HRPE) in vitro. METHOD: HRPE were
      cultured for 24 hours with the substances being tested (glucose, EDPs), alone or
      in combination. Additionally, the cells were treated with atorvastatin in two
      different concentrations (1 or 10 MUM). After incubation, total cellular RNA was
      extracted and used for gene expression evaluation. Gene expression was measured
      using the real-time RT-PCR technique. RESULTS: Glucose, EDPs and atorvastatin had
      no impact on TIMP-1 and TIMP-3 expression. HRPE cells treated with glucose or
      EDPs with the addition of atorvastatin had a statistically significant decrease
      of TIMP-2 expression; glucose alone decreased MMP-1 expression. Atorvastatin
      decreased expression of all assessed genes, except TIMP-1 and TIMP-3 in a dose
      dependent manner. CONCLUSIONS: Our results confirm the importance of MMPs and
      TIMPs in retinal vascular biology. Atorvastatin-induced MMPs gene expression can
      deeply affect extracellular matrix turnover, which may play an important role in
      the progression of ocular diseases.

PMID- 24904927
TI  - Graves' disease, Celiac disease and liver function abnormalities in a patient-
      clinical manifestation and diagnostic difficulties.
AB  - Autoimmune diseases due to probable common pathogenesis tend to coexist in some
      patients. Complex clinical presentation with diverse timing of particular
      symptoms and sophisticated treatment with numerous side effects, may cause
      diagnostic difficulties, especially in children. The paper presents diagnostic
      difficulties and pitfalls in a child with Graves' disease, celiac disease and
      liver function abnormalities. 

PMID- 24904928
TI  - Genetic diversity of F1 and F2 interspecific hybrids between dwarf birch (Betula
      nana L.) and Himalayan birch (B. utilis var. jacquemontii (Spach) Winkl.
      'Doorenbos') using RAPD-PCR markers and ploidy analysis.
AB  - Crosses between Betula nana and B. utilis 'Doorenbos' were undertaken in order to
      obtain interspecific hybrids which could be characterized by wide spreading
      stems, strong branching habit, decorative clear white bark and an interesting
      shape of purple leaves. The research purpose was to examine genetic diversity of
      the 16 F1 and F2 putative progenies by using the RAPD-PCR method and the ploidy
      analysis. A total of 242 RAPD markers were scored with 24 primers and 220 (90.9%)
      polymorphic bands were found. In the NJ dendrogram, cluster I consisted of the
      female parent--B. nana and 12 hybrids and cluster II grouped the male parent--B.
      utilis 'Doorenbos' with 4 hybrids (F2/2, F1/8, F1/7 and F2/1). The 2-D scaling by
      PCoA was in agreement with the similarity index, i.e. two hybrids (F1/8, F2/2)
      grouped with the male parent while others with female parent. Classification of
      the hybrid plants by chromosome counting demonstrated that 13 hybrids were
      confirmed with accurate chromosome counts as being diploid (2n=2x=28) and 3
      plants (F1/7, F1/8, F2/2) as triploid with 42 chromosomes.

PMID- 24904929
TI  - Pilot study on feasibility of application of gas chromatography for the
      assessment of acrylamide concentration in sewage sludge.
AB  - The aim of this study was to determine the possibility of using gas
      chromatography to measurement of the acrylamide concentration in sewage sludge.
      Acrylamide, as a toxic substance, is not indifferent to human health, but it is
      used in the production of plastics, dyes, adhesives, cosmetics, mortar, as well
      as a coagulant for water treatment, wastewater or sewage sludge conditioning.
      Determination of acrylamide by gas chromatography was based on standard: EPA
      Method 8032A "Acrylamid by gas chromatography." It consists of a bromination
      reaction of the compound in the presence of dibromopropendial derivative, a
      triple extraction with the ethyl acetate, a concentration of the eluate sample up
      to the 1 ml volume, and an analysis by the gas chromatography using an electron
      capture detector (ECD). The acrylamide concentration of was calculated according
      to the formula presented in the mentioned standard. All samples were performed
      twice (the difference between the results was not greater than 10%), and the
      average value of the four samples was 17.64 ug/L(-1). The presence of acrylamide
      in sewage sludge has been confirmed. 

PMID- 24904930
TI  - Biocatalytic synthesis of delta-gluconolactone and epsilon-caprolactone
      copolymers.
AB  - The biodegradability and biocompatibility properties of epsilon-caprolactone
      homopolymers place it as a valuable raw material, particularly for controlled
      drug delivery and tissue engineering applications. However, the usefulness of
      such materials is limited by their low hydrophilicity and slow biodegradation
      rate. In order to improve polycaprolactone properties and functionalities,
      copolymerization of epsilon-caprolactone with delta-gluconolactone was
      investigated. Since enzymatic reactions involving sugars are usually hindered by
      the low solubility of these compounds in common organic solvents, finding the
      best reaction medium was a major objective of this research. The optimal
      copolymerization conditions were set up by using different organic media (solvent
      and solvents mixtures), as well as solvent free systems that are able to dissolve
      (completely or partially) sugars, and are nontoxic for enzymes. Native and
      immobilized lipases by different immobilization techniques from Candida
      antarctica B and Thermomyces lanuginosus have been used as biocatalyst at 80
      degrees C. Although the main copolymer amount was synthesized in DMSO:t-BuOH
      (20:80) medium, the highest polymerization degrees, up to 16 for the copolymer
      product, were achieved in solventless conditions. The products, cyclic and linear
      polyesters, have been characterized by FT-IR and MALDI-TOF MS analysis. The
      reaction product analysis revealed the formation of cyclic products that could be
      the major impediment of further increase of the chain length. 

PMID- 24904931
TI  - Increased levels of antibodies against heat shock proteins in stroke patients.
AB  - Ischemic stroke is the second leading cause of death worldwide. One of the main
      risk factors of the ischemic stroke is atherosclerosis which is a chronic
      inflammatory and immune-mediated disease. Bacterial infections generate specific
      human antibodies against various antigens, including Hsps. It has been
      demonstrated that Hsps are selectively overexpressed in the atherosclerotic
      lesions. The amino acid sequence homology between human and bacterial Hsps may
      lead to an autoimmune response by immunological cross-reaction. Such immune
      response against Hsps overexpressed in the blood vessels under stressful
      conditions may contribute to inflammatory processes and subsequent development of
      atherosclerosis. In this study we determined the antibody levels against
      bacterial and human Hsp by ELISA in blood plasma obtained from stroke patients.
      Using ANOVA we analyzed levels of Hsp-antibodies in control and patient groups
      and correlate them with several stroke risk factors. The group of stroke patients
      had elevated levels of anti-Hsp antibodies compared to the control group. We also
      discovered an antibody level increase in patients that previously underwent
      another stroke. Our data provide evidence that autoimmunity could underlie
      formation of atherosclerosis plaque leading to stroke. 

PMID- 24904932
TI  - Cryptic sex in Symbiodinium (Alveolata, Dinoflagellata) is supported by an
      inventory of meiotic genes.
AB  - Symbiodinium encompasses a diverse clade of dinoflagellates that are ecologically
      important as symbionts of corals and other marine organisms. Despite decades of
      study, cytological evidence of sex (karyogamy and meiosis) has not been
      demonstrated in Symbiodinium, although molecular population genetic patterns
      support the occurrence of sexual recombination. Here, we provide additional
      support for sex in Symbiodinium by uncovering six meiosis-specific and 25 meiosis
      related genes in three published genomes. Cryptic sex may be occurring in
      Symbiodinium's seldom-seen free-living state while being inactive in the
      symbiotic state.

PMID- 24904933
TI  - Comparison of corneal deformation parameters after SMILE, LASEK, and femtosecond
      laser-assisted LASIK.
AB  - PURPOSE: To investigate the differences in corneal deformation parameters after
      femtosecond laser small incision lenticule extraction (SMILE), laser-assisted
      subepithelial keratomileusis (LASEK), and femtosecond laser-assisted LASIK (FS
      LASIK). METHODS: In this retrospective study, 17 eyes of 17 patients after SMILE,
      18 eyes of 18 patients after LASEK, and 17 eyes of 17 patients after FS-LASIK
      were included. Corneal deformation parameters were measured with the CorVis ST
      tonometer (Oculus Optikgerate GmbH, Wetzlar, Germany) 3 months postoperatively.
      RESULTS: The mean value of deformation amplitude of the FS-LASIK group was
      significantly higher than that of the LASEK group (P = .022). The mean value of
      applanation time (applanation 1) of the LASEK group was significantly higher than
      that of the FS-LASIK group (P = .038). No significant difference was detected in
      the mean values of deformation amplitude and applanation time (applanation 1) (P
      > .05) between the LASEK and SMILE groups or between the SMILE and FS-LASIK
      groups. Multiple linear regression model analysis revealed that after adjustment
      for age and preoperative central corneal thickness and manifest refraction
      spherical equivalent, the significance of the difference in the mean values of
      applanation time (applanation 1) and deformation amplitude between the LASEK and
      FS-LASIK groups were P = .084 and .059, respectively. In all three groups, the
      values of applanation 1 negatively correlated to those of applanation time
      (applanation 2) (SMILE: r = -0.577, P = .015; LASEK: r = -0.833, P < .001; FS
      LASIK: r = -0.516, P = .034) and deformation amplitude (SMILE: r = -0. 556, P =
      .021; LASEK: r = -0.877, P < .001; FS-LASIK: r = -0.509, P = .037). CONCLUSIONS:
      Applanation time (applanation 1) and deformation amplitude (as measured with the
      CorVis ST tonometer) may be helpful in assessing corneal biomechanical changes
      after corneal refractive surgery. The relations between these parameters should
      be discussed in further studies.

PMID- 24904934
TI  - Cardiologists urged to reduce inappropriate  radiation exposure.

PMID- 24904936
TI  - Strengthening the BVA's influence in Europe.

PMID- 24904935
TI  - Too busy for a sabbatical abroad: Lars Wallentin, the all-Swedish, yet
      international, superstar cardiologist.

PMID- 24904937
TI  - After the treated mole.

PMID- 24904938
TI  - Revision of the diagnosis of a case of hereditary hemolytic anemia by supravital
      staining.

PMID- 24904939
TI  - Synthetic biology: back to the basics.

PMID- 24904940
TI  - With sadness on the passing of Louis Gifford a patient centred practitioner.

PMID- 24904942
TI  - Adrian Barnes MSc(Ost) D.O, principal of the European School of Osteopathy (ESO).

PMID- 24904941
TI  - Robin Kirk DO ND MSc 1939-2014.

PMID- 24904943
TI  - Propargylic cation-induced intermolecular  electrophilic addition-semipinacol 
      rearrangement.
AB  - A novel propargylic electrophile-induced tandem intermolecular addition
      semipinacol rearrangement was developed efficiently under mild conditions.
      Various allylic silylether substrates as well as Co-complexed propargylic species
      were applicable to this protocol and gave a series of synthetically useful beta
      propargyl spirocyclic ketones in moderate to good yields. Its synthetic
      application was also demonstrated by an efficient construction of the key
      tricyclic moiety of daphlongamine E.

PMID- 24904944
TI  - Electrophoretic separation in a microfluidic  paper-based analytical device with
      an on-column  wireless electrogenerated chemiluminescence  detector.
AB  - In this work, a microfluidic paper-based analytical device was further exploited
      by coupling with an electrophoretic separation technique for the first time. A
      low-cost, simple, portable, and disposable microfluidic paper-based
      electrophoretic device with an on-column wireless electro-generated
      chemiluminescence detector was demonstrated.

PMID- 24904945
TI  - Facile method to attach transition metal ions to the surface of anatase TiO(2)
      nanorods.
AB  - We report a robust, low-cost method to attach transition metal ions directly to
      the surface of anatase TiO2 rod-shaped nanocrystals with preservation of the host
      nanocrystal morphology and phase. The procedure has been optimized to achieve
      quantitative control of metal ion loading on the surface of the nanorods. The
      metal ion can be attached to the nanocrystal surface up to fullmonolayer
      coverage, after which the surface becomes saturated and there is no further
      addition.

PMID- 24904946
TI  - Why the labour ward first?

PMID- 24904947
TI  - Trapped in a hospital setting.

PMID- 24904948
TI  - Private versus government funded: how two Uganda hospitals differed.

PMID- 24904949
TI  - Labour drugs associated with drop in breastfeeding rates.

PMID- 24904950
TI  - VBAC and the birthing pool: advice wanted.

PMID- 24904952
TI  - New technology for fetal testing.

PMID- 24904951
TI  - From Devon to Tonga: one midwife's experience of life in Sudan.

PMID- 24904953
TI  - Disillusioned and disgruntled too.

PMID- 24904954
TI  - Hepatitis E infection in patients with severe acute alcoholic hepatitis.
AB  - BACKGROUND & AIMS: Hepatitis E virus (HEV) infection is a known cause of acute-on
      chronic liver failure in developing countries, but its implication in Western
      countries remains unknown. HEV burden in the setting of severe acute alcoholic
      hepatitis (AAH) was assessed. METHODS: Patients admitted for severe AAH from 2007
      to 2013, with available sera and histologically proven AAH, were included and
      managed according to current European guidelines. At admission, clinical and
      biological characteristics were collected; HEV serology and RNA detection were
      retrospectively performed. RESULTS: Eighty-four patients were included. Mean age
      was 50.8 +/- 9.6 years, 65.5% were male, 91.7% were cirrhotic and 33.3% presented
      with encephalopathy. Mean MELD and Maddrey scores were respectively 32.4 +/- 11.4
      and 73.3 +/- 37. Liver biopsy showed mild, moderate and severe hepatitis in 25
      (29.8%), 23 (27.4%) and 32 (38.1%) patients respectively. Steroids were given to
      61 patients (72.6%) of whom 35 (57.4%) presented corticoresistance (mean Lille
      score: 0.78 +/- 0.21). During hospitalization, 24 patients (28.6%) died and 11
      (13.1%) were transplanted. Three patients (3.6%) presented markers of acute HEV
      infection and 21 (25%) markers of past HEV infection. Patient with acute
      infection were men, cirrhotic, and 2/3 presented with encephalopathy. Steroids
      were given to two patients without any response. The third patient died. None
      were transplanted. CONCLUSIONS: A substantial proportion of patients with severe
      AAH had markers of acute HEV infection, with similar clinical presentation and
      outcomes. Larger studies are needed to evaluate HEV impact on AAH management,
      resistance to steroids, and outcome.

PMID- 24904955
TI  - The reverse fluorine Perlin-like effect and related stereoelectronic
      interactions.
AB  - A similar effect to the well-known reverse Perlin effect was observed on the
      (1)JC-F coupling constants of alpha- and beta-d-glucopyranosyl fluoride
      tetracetate, both in nonpolar and polar solution. This can be called "reverse
      fluorine Perlin-like effect", and it is shown to be ruled by dipolar interactions
      rather than by hyperconjugation. The reverse fluorine Perlin-like effect does not
      have a general relationship with the anomeric effect, and it can be useful to
      determine the structure and stereochemistry of organofluorine compounds. 

PMID- 24904956
TI  - Seamless Phase I/II Adaptive Design for Oncology Trials of Molecularly Targeted
      Agents.
AB  - In dose-finding trials of chemotherapeutic agents, the goal of identifying the
      maximum tolerated dose is usually determined by considering information on
      toxicity only, with the assumption that the highest safe dose also provides the
      most promising outlook for efficacy. Trials of molecularly targeted agents
      challenge accepted dose-finding methods because minimal toxicity may arise over
      all doses under consideration and higher doses may not result in greater
      response. In this article, we propose a new early-phase method for trials
      investigating targeted agents. We provide simulation results illustrating the
      operating characteristics of our design. 

PMID- 24904958
TI  - Evaluating the MEDLINE Core Clinical Journals filter: data-driven evidence
      assessing clinical utility.
AB  - RATIONALE, AIMS AND OBJECTIVES: MEDLINE offers the Core Clinical Journals filter
      to limit to clinically useful journals. To determine its effectiveness for
      searching and patient-centric decision making, this study compared literature
      used for Morning Report in Internal Medicine with journals in the filter. METHOD:
      An EndNote library with references answering 327 patient-related questions during
      Morning Report from 2007 to 2012 was exported to a file listing variables
      including designated Core Clinical Journal, Impact Factor, date used and medical
      subject. Bradford's law of scattering was applied ranking the journals and
      reflecting their clinical utility. Recall (sensitivity) and precision of the Core
      Morning Report journals and non-Core set was calculated. This study applied
      bibliometrics to compare the 628 articles used against these criteria to
      determine journals impacting decision making. RESULTS: Analysis shows 30% of
      clinically used articles are from the Core Clinical Journals filter and 16% of
      the journals represented are Core titles. When Bradford-ranked, 55% of the top 20
      journals are Core. Articles <5 years old furnish 63% of sources used. Among the
      63 Morning Report subjects, 55 have <50% precision and 41 have <50% recall
      including 37 subjects with 0% precision and 0% recall. CONCLUSIONS: Low usage of
      publications within the Core Clinical Journals filter indicates less relevance
      for hospital-based care. The divergence from high-impact medicine titles suggests
      clinically valuable journals differ from academically important titles. With few
      subjects demonstrating high recall or precision, the MEDLINE Core Clinical
      Journals filter may require a review and update to better align with current
      clinical needs.

PMID- 24904957
TI  - Overweight, high blood pressure and impaired fasting glucose in Uyghur, Han, and
      Kazakh Chinese children and adolescents.
AB  - OBJECTIVES: To investigate whether the levels of blood pressure and fasting
      glucose differ among Chinese children of three different ethnicities (i.e.,
      Uyghurs, Kazakhs, and Hans) and whether the differences are explained by
      childhood obesity. METHODS: A school-based cross-sectional study was conducted in
      a large three ethnic pediatric population (n = 6633), whose ages ranged from 7 to
      18 years. Anthropometrics and blood pressure were measured using standard
      protocols. Fasting glucose was measured in a subset of children (n = 2295) who
      were randomly selected based on ethnicity and age. The age-sex stratified Chinese
      national cut-offs were used to define obesity and high blood pressure (HBP). The
      prevalence of HBP, impaired fasting glucose (IFG), mean levels of blood pressure,
      and glucose were compared among three ethnic groups. RESULTS: 2142 Uyghurs, 2078
      Han, and 1997 Kazakhs were analyzed. After adjusting for age and body mass index
      (BMI), the mean blood pressure for Uyghurs was on average, 2-4 mm Hg lower than
      those for Hans and Kazakhs. Kazakhs had the lowest mean fasting glucose compared
      with Hans and Uyghurs (4.5 vs. 5.0 vs. 4.8 mmol/L, respectively). The differences
      in blood pressure and fasting glucose persisted even after adjusting for age and
      BMI, and the differences among ethnic groups in blood pressure levels and fasting
      glucose levels were observed as early as 7-9 years of age. CONCLUSIONS: The
      prevalence of HBP and IFG differed significantly among Uyghurs, Hans, and
      Kazakhs, and the ethnic differences observed in childhood were consistent with
      those observed in adults from the same region. While childhood obesity is a
      significant risk factor for hypertension and elevated glucose, the differences
      among ethnic groups were not explained by obesity alone.

PMID- 24904959
TI  - A general synthetic approach for ordered mesoporous metal sulfides.
AB  - Mesoporous non-silica materials have shown unique properties in many fields such
      as heterogeneous catalysis and energy conversion and storage. Many studies have
      been devoted to the synthesis of mesoporous transition-metal-containing
      materials. However, the range of materials that can be made is mainly limited to
      oxides. In this work, we developed an oxide-to-sulfide transformation approach as
      a general synthetic method to prepare ordered mesoporous metal sulfides. Three
      first-row transition-metal sulfides, FeS2, CoS2, and NiS2, with highly ordered
      mesoporous structures and crystalline walls have been successfully synthesized
      for the first time. A preliminary investigation was performed to explore the
      photocatalytic properties of the newly synthesized mesoporous metal sulfides. All
      of the mesoporous metal sulfides exhibited higher activity than their bulk
      counterparts for the photocatalytic degradation of methylene blue dye under
      visible-light irradiation. More importantly, the preparation method introduced in
      this work may be extended to other mesoporous metal chalcogenides for a variety
      of potential applications. 

PMID- 24904960
TI  - Relationship between stearoyl-CoA desaturase 1 gene expression, relative protein
      abundance, and its fatty acid products in bovine tissues.
AB  - Stearoyl-CoA desaturase 1 (SCD1) greatly contributes to the unsaturated fatty
      acids present in milk and meat of cattle. The SCD1 enzyme introduces a double
      bond into certain saturated fatty acyl-CoAs producing monounsaturated fatty acids
      (MUFA). The SCD1 enzyme also has been shown to be active in the bovine mammary
      gland converting t11 18:1 (vaccenic acid) to c9 t11 conjugated linoleic acid
      (CLA). The objective of this study was to determine any association between the
      gene expression of SCD1 and occurrence of its products (c9 14:1, c9 16:1, c9
      18:1, and c9 t11 18:2) in various bovine tissues. Tissue samples were obtained
      from lactating Holstein cows (n=28) at slaughter, frozen in liquid nitrogen and
      stored at -80  degrees C. Total RNA was extracted and converted to complementary
      DNA for quantitative real time polymerase chain reaction (PCR) analysis of the
      SCD1 gene. Extracted lipid was converted to fatty acid methyl esters and analysed
      by GC. Tissues varied in expression of SCD1 gene with mammary, cardiac,
      intestinal adipose, and skeletal muscle expressing greater copy number as
      compared with lung, large intestine, small intestine and liver (371, 369, 328,
      286, 257, 145, 73, and 21 copies/ng RNA, respectively). Tissues with high mRNA
      expression of SCD1 contained greater SCD1 protein whereas detection of SCD1
      protein in tissues with low SCD1 mRNA expression was very faint or absent. Across
      tissues, the desaturase indices for c9 18:1 (r=0.24) and sum of SCD products
      (r=0.20) were positively correlated with SCD1 gene expression (P<0.01 for both).
      Within each tissue, the relationship between SCD1 gene expression and the
      desaturase indices varied. No correlation was detected between SCD1 expression
      and desaturase indices in the liver, large and small intestines, lung, cardiac or
      skeletal muscles. Positive correlations, however, were detected between SCD1
      expression and the desaturase indices in intestinal adipose tissue (P<0.02 for
      all) except 14:1, whereas only c9 18:1, c9 t11 18:2 and sum of all desaturase
      indices were positively correlated with SCD1 expression in mammary tissue (P < or
      = 0.03). Overall, the relationship between SCD1 gene expression and occurrence of
      its products seems to be tissue specific.

PMID- 24904961
TI  - Synthesis and in vivo SAR study of indolin-2-one-based multi-targeted inhibitors
      as potential anticancer agents.
AB  - A series of indolin-2-one analogues were designed and synthesized, and all of
      them exhibited excellent in vitro potency. The structure and in vivo activity or
      toxicity relationship (in-vivo SAR) investigation of indolin-2-one structural
      analogues was carried out. In vivo efficacy studies indicated that 3b
      significantly suppressed tumor growth in HT-29 and NCI-H460 xenografts without
      causing significant loss of body weight. Kinase assay showed that compound 3b
      effectively inhibited the VEGFR-2, VEGFR-3, FLT3, Ret and PDGFR-beta kinases, but
      had little effect on the VEGFR-1 kinase. Besides, 3b showed higher selectivity
      for VEGFR-2 compared with PDGFR-beta. On the basis of its selectivity and safety
      properties, 3b was identified as a drug candidate for the treatment of cancer.

PMID- 24904962
TI  - New mixed ligand zinc(II) complexes based on the antiepileptic drug sodium
      valproate and bioactive nitrogen-donor ligands. Synthesis, structure and
      biological properties.
AB  - Starting from the precursor [Zinc Valproate complex] (1), new mixed ligand
      zinc(II) complexes of valproic acid and nitrogen-based ligands, formulating as,
      [Zn(valp)22,9-dmphen] (2), [Zn2(valp)4(quin)2] (3), [Zn(valp)2(2-ampy)2] (4), and
      [Zn(valp)2(2-ampic)2] (5) (valp = valproate, 2,9-dmphen = 2,9-dimethyl-1,10
      phenanthroline, quin = quinoline, 2-ampy = 2-aminopyridine, 2-ampic = 2-amino-6
      picoline) were synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR
      and UV-Vis spectrometry. The crystal structures of complexes 2, 3 and 4 were
      determined using single-crystal X-ray diffraction. The complexes were also
      evaluated for their anti-bacterial activity using in-vitro agar diffusion method
      against three Gram-positive (Micrococcus luteus, Staphylococcus aureus, and
      Bacillus subtilis) and three Gram-negative (Escherichia coli, Klebsiella
      pneumoniae, and Proteus mirabilis) species. Complex 2 showed considerable
      activity against all tested microorganisms and the effect of complexation on the
      anti-bacterial activity of the parent ligand of 2 was also investigated. The anti
      bacterial activity of 2,9-dmphen against Gram-negative bacteria was enhanced upon
      complexation with zinc valproate. On the other hand, complexes 1 and 3 showed
      weak inhibition activity against the tested species and complexes 4 and 5 didn't
      show any activity at all. Two methods were used for testing the inhibition of
      ferriprotoporphyrinIX bio-mineralization: a semi-quantitative micro-assay and a
      previously self-developed quantitative in-vitro method. Both were used to study
      the efficiency of these complexes in inhibiting the formation of the Malaria
      pigment which considered being the target of many known anti-malarial drugs such
      as Chloroquine and Amodiaquine. Results showed that the efficiency of complex 2
      in preventing the formation of beta-Hematin was 80%. The efficiency of
      Amodiaquine as a standard drug was reported to give 91%.

PMID- 24904963
TI  - New insights into the biological properties of Crocus sativus L.: chemical
      modifications, human monoamine oxidases inhibition and molecular modeling
      studies.
AB  - Although there are clinical trials and in vivo studies in literature regarding
      the anxiolytic and antidepressant activities of the components of Crocus sativus
      L., their effects on the human monoamine oxidases (hMAO-A and hMAO-B), enzymes
      which are involved in mental disorders and neurodegenerative diseases, have not
      yet been investigated. We have thus examined the hMAO inhibitory activities of
      crocin and safranal (the most important active principles in saffron) and,
      subsequently, designed a series of safranal derivatives to evaluate which
      chemical modifications confer enhanced inhibition of the hMAO isoforms. Docking
      simulations were performed in order to identify key molecular recognitions of
      these inhibitors with both isoforms of hMAO. In this regard, different mechanisms
      of action were revealed. This study concludes that safranal and crocin represent
      useful leads for the discovery of novel hMAO inhibitors for the clinical
      management of psychiatric and neurodegenerative disorders.

PMID- 24904964
TI  - Effect of carbon chain length on biological activity of novel palladium (II)
      complexes.
AB  - A series of complexes [Pd(L1)(Phen)].2H2O (1), [Pd(L2)(Phen)].H2O (2),
      [Pd(L3)(Phen)].H2O (3), [Pd(L4)(Phen)].2H2O (4) and [Pd(L5)(Phen)].2H2O (5) were
      prepared. The complexes were characterized by IR, (1)H NMR, elemental analysis,
      and single-crystal X-ray diffractometry. The binding of the complexes was
      investigated by fluorescence spectrum and UV spectrum, showing the ability of
      interaction with DNA of intercalative mode. Gel electrophoresis assay
      demonstrated the ability of the complexes to cleave the pBR322 DNA. Moreover, the
      five complexes bind to DNA with different binding affinities, in ascending order:
      complex 1 < 2<3 < 4 < 5. Evaluation of cytotoxic activity of the complexes
      against five different cancer cell lines proved that the complexes exhibited
      cytotoxic specificity and significant cancer cell inhibitory rate.

PMID- 24904965
TI  - Design, synthesis and systematic evaluation of cytotoxic 3
      heteroarylisoquinolinamines as topoisomerases inhibitors.
AB  - A series of 3-heteroarylisoquinolinamines were designed, synthesized and
      evaluated for cytotoxicity, topoisomerases (topos) inhibitory activities and cell
      cycle inhibition. Several of the 3-heteroarylisoquinolines exhibited selective
      cytotoxicity against human ductal breast epithelial tumor (T47D) cells over non
      cancerous human breast epithelial (MCF-10A) and human prostate cancer (DU145)
      cells. Most of the derivatives showed greater cytotoxicity in human colorectal
      adenocarcinoma (HCT-15) cells than camptothecin (CPT), etoposide and doxorubicin
      (DOX). Generally, 3-heteroarylisoquinolinamines displayed greater affinity for
      topo I than topo II. 3-Heteroarylisoquinolinamines with greater topo I inhibitory
      effect exhibited potent cytotoxicity. Piperazine-substituted derivative, 5b, with
      potent topo I and moderate topo II activities intercalated between DNA bases and
      interacted with topos through H-bonds at the DNA cleavage site of a docking
      model. Moreover, flow cytometry indicated that cytotoxic 3
      heteroarylisoquinolinamines led to accumulation of human cervical (HeLa) cancer
      cells in the different phases of the cell cycle before apoptosis. Taken together,
      3-heteroarylisoquinolinamines possessed potent cytotoxicity with topos and cell
      cycle inhibitory activities.

PMID- 24904966
TI  - Discovery of potent anticancer agent HJC0416, an orally bioavailable small
      molecule inhibitor of signal transducer and activator of transcription 3 (STAT3).
AB  - In a continuing effort to develop orally bioavailable small-molecule STAT3
      inhibitors as potential therapeutic agents for human cancer, a series of novel
      diversified analogues based on our identified lead compound HJC0149 (1) (5-chloro
      N-(1,1-dioxo-1H-1lambda(6)-benzo[b]thiophen-6-yl)-2-hydroxybenzamide, Eur. J.
      Med. Chem. 2013, 62, 498-507) have been rationally designed, synthesized, and
      pharmacologically evaluated. Molecular docking studies and biological
      characterization supported our earlier findings that the O-alkylamino-tethered
      side chain on the hydroxyl group is an effective and essential structural
      determinant for improving biological activities and druglike properties of these
      molecules. Compounds with such modifications exhibited potent antiproliferative
      effects against breast and pancreatic cancer cell lines with IC50 values from low
      micromolar to nanomolar range. Among them, the newly discovered STAT3 inhibitor
      12 (HJC0416) displayed an intriguing anticancer profile both in vitro and in vivo
      (i.p. & p.o.). More importantly, HJC0416 is an orally bioavailable anticancer
      agent as a promising candidate for further development.

PMID- 24904967
TI  - Discovery of HDAC inhibitors with potent activity against multiple malaria
      parasite life cycle stages.
AB  - In this work we investigated the antiplasmodial activity of a series of HDAC
      inhibitors containing an alkoxyamide connecting-unit linker region. HDAC
      inhibitor 1a (LMK235), previously shown to be a novel and specific inhibitor of
      human HDAC4 and 5, was used as a starting point to rapidly construct a mini
      library of HDAC inhibitors using a straightforward solid-phase supported
      synthesis. Several of these novel HDAC inhibitors were found to have potent in
      vitro activity against asexual stage Plasmodium falciparum malaria parasites.
      Representative compounds were shown to hyperacetylate P. falciparum histones and
      to inhibit deacetylase activity of recombinant PfHDAC1 and P. falciparum nuclear
      extracts. All compounds were also screened in vitro for activity against
      Plasmodium berghei exo-erythrocytic stages and selected compounds were further
      tested against late stage (IV and V) P. falciparum gametocytes. Of note, some
      compounds showed nanomolar activity against all three life cycle stages tested
      (asexual, exo-erythrocytic and gametocyte stages) and several compounds displayed
      significantly increased parasite selectivity compared to the reference HDAC
      inhibitor suberoylanilide hydroxamic acid (SAHA). These data suggest that it may
      be possible to develop HDAC inhibitors that target multiple malaria parasite life
      cycle stages.

PMID- 24904968
TI  - Design of alpha7 nicotinic acetylcholine receptor ligands in quinuclidine,
      tropane and quinazoline series. Chemistry, molecular modeling, radiochemistry, in
      vitro and in rats evaluations of a [(18)F] quinuclidine derivative.
AB  - In this report, we describe the synthesis of a novel library of alpha7 nAChR
      ligands based on the modulation of the quinuclidine, quinazoline and tropane
      moieties. Spirane derivatives were newly synthesized under stereo specific 1,3
      dipolar cylcoadditions. Only amide derivatives bonded efficiently to the receptor
      with Ki measured between 14 and 133 nM. The best fluorinated candidate was
      selected and radiolabeled. The potent [(18)F]4 PET tracer was evaluated in rats
      and its brain accumulation quantified.

PMID- 24904970
TI  - Photochemistry of fumaronitrile radical anion and its clusters.
AB  - The photodetachment and photochemistry of the radical anion of fumaronitrile
      (trans-1,2-dicyanoethylene) and its clusters are investigated using photoelectron
      imaging and photofragment spectroscopy. We report the first direct spectroscopic
      determination of the adiabatic electron affinity (EA) of fumaronitrile (fn) in
      the gas phase, EA = 1.21 +/- 0.02 eV. This is significantly smaller than one-half
      the EA of tetracyanoethylene (TCNE). The singlet-triplet splitting in
      fumaronitrile is determined to be DeltaES-T <= 2.6 eV, consistent with the known
      properties. An autodetachment transition is observed at 392 and 355 nm and
      assigned to the (2)Bu anionic resonance in the vicinity of 3.3 eV. The results
      are in good agreement with the predictions of the CCSD(T) and EOM-XX-CCSD(dT) (XX
      = IP, EE) calculations. The H2O and Ar solvation energies of fn(-) are found to
      be similar to the corresponding values for the anion of TCNE. In contrast, a very
      large (0.94 eV) photodetachment band shift, relative to fn(-), is observed for
      (fn)2(-). In addition, while the photofragmentation of fn(-), fn(-).Ar, and fn(
      )(H2O)1,2 yielded only the CN(-) fragment ions, the dominant anionic
      photofragment of (fn)2(-) is the fn(-) monomer anion. The band shift, exceeding
      the combined effect of two water molecules, and the fragmentation pattern,
      inconsistent with an intact fn(-) chromophore, rule out an electrostatically
      solvated fn(-).fn structure of (fn)2(-) and favor a covalently bound dimer anion.
      A C2 symmetry (fn)2(-) structure, involving a covalent bond between the two fn
      moieties, is proposed. 

PMID- 24904969
TI  - Design and synthesis of calcium responsive magnetic resonance imaging agent: Its
      relaxation and luminescence studies.
AB  - Calcium concentration modulation both inside and outside cell is of considerable
      interest for nervous system function in normal and pathological conditions. MRI
      has potential for very high spatial resolution at molecular/cellular level.
      Design, synthesis and evaluation of Gd-DO3A-AME-NPHE, a calcium responsive MRI
      contrast agent is presented. The probe is comprised of a Gd(3+)-DO3A core coupled
      to iminoacetate coordinating groups for calcium induced relaxivity switching. In
      the absence of Ca(2+) ions, inner sphere water binding to the Gd-DO3A-AME-NPHE is
      restricted with longitudinal relaxivity, r1 = 4.37 mM(-1) s(-1) at 4.7 T.
      However, addition of Ca(2+) triggers a marked enhancement in r1 = 6.99 mM(-1) s(
      1) at 4.7 T (60% increase). The construct is highly selective for Ca(2+) over
      competitive metal ions at extracellular concentration. The r1 is modulated by
      changes in the hydration number (0.2 to 1.05), which was confirmed by
      luminescence emission lifetimes of the analogous Eu(3+) complex. T1 phantom
      images establish the capability of complex of visualizing changes in [Ca(2+)] by
      MRI.

PMID- 24904971
TI  - Grizzly bear hair reveals toxic exposure to mercury through salmon consumption.
AB  - Mercury obtained from the diet accumulates in mammalian hair as it grows thus
      preserving a record of mercury intake over the growth period of a given hair
      segment. We adapted a microanalysis approach, using laser ablation inductively
      coupled plasma mass spectrometry, to characterize temporal changes in mercury
      exposure and uptake in wild and captive grizzly bears. Captive grizzlies fed
      diets containing known and varied amounts of mercury provided data to allow
      prediction of Hg ingestion rates in wild bears. Here, we show, for the first
      time, that 70% of the coastal grizzly bears sampled had Hg levels exceeding the
      neurochemical effect level proposed for polar bears. In a context where the
      international community is taking global actions to reduce Hg emissions through
      the "Minamata Convention on Mercury", our study provides valuable information on
      the exposure to mercury of these grizzly bears already under many threats. 

PMID- 24904974
TI  - Halogen-bonding-induced hydrogen transfer to C?N bond with Hantzsch ester.
AB  - Several bidentate dihydroimidazolines were prepared and investigated as catalysts
      for hydrogen transfer reduction of C?N bond with Hantzsch ester. Highly efficient
      reactions were observed for quinolines and imines with low catalyst loading of 2
      mol %. The presence of halogen bonding was elucidated using NMR studies and
      isothermal calorimeric titrations. Binding constants of the XB donors were also
      measured using isothermal calorimeric titrations (ITC). 

PMID- 24904976
TI  - Nanoparticulate carrier system: a novel treatment approach for hyperlipidemia.
AB  - Hyperlipidemia is a prevailing risk factor that leads to development and
      progression of atherosclerosis and consequently cardiovascular diseases. Several
      antihyperlipidemic drugs are having various disadvantages such as low water
      solubility and poor bioavailabilty due to presystemic gastrointestinal clearance.
      Thus, there is a considerable need for the development of efficient delivery
      methods and carriers. This review focuses on the importance and role of various
      nanoparticulate systems as carrier for antihyperlipidemic drugs in the treatment
      of hyperlipidemia. Some nanoparticle technology-based products are approved by
      FDA for effective treatment of hyperlipidemia, namely Tricor(r) by Abbott
      Laboratories (Chicago, IL, USA) and Triglide(r) by Skye Pharma (London, UK).
      Efforts to address each of these issues are going on, and should remain the focus
      on the future studies and look forward to many more clinical products in the
      future. 

PMID- 24904975
TI  - Preparation, characterization, and anticancer efficacy of evodiamine-loaded PLGA
      nanoparticles.
AB  - Evodiamine (EVO) is a plant-derived indolequinazoline alkaloid with potential
      anticancer activity. However, low bioavailability caused by its poor water
      solubility limits it anticancer efficacy in clinic. To enhance the solubility and
      improve the bioavailability of EVO, a delivery system based on poly (lactic-co
      glycolic acid) (PLGA) nanoparticles loaded with EVO (EVO-PLGA NPs) for treating
      breast cancer was prepared in this study. The physicochemical characterization
      and in vitro antitumor evaluation of EVO-PLGA NPs were determined. EVO-PLGA NPs
      could persistently control the release of EVO for 180 h. 3-[4,5-Dimethyl-2
      thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assessment and colony formation
      assay showed that EVO-PLGA NPs could enhance the toxicity and the proliferation
      inhibition effect of EVO on MCF-7 breast cancer cells. EVO-PLGA NPs did not
      strengthen G2/M arrest effect of EVO-treated cells after 24h incubation.
      Meanwhile, EVO-PLGA NPs could increase the expression of cyclin B1 and decrease
      the expression of beta-actin. Taken together, these results suggested that -PLGA
      NPs is promising for improving anticancer efficacy of EVO in breast cancer
      therapy. 

PMID- 24904977
TI  - Posterior hypothalamic modulation of ocular-responsive trigeminal subnucleus
      caudalis neurons is mediated by Orexin-A and Orexin1 receptors.
AB  - Orexin-A (OxA) is synthesized in posterior and lateral regions of the
      hypothalamus and contributes to homeostatic regulation of body functions
      including pain modulation. To determine if orexinergic mechanisms contribute to
      posterior hypothalamus (PH)-induced modulation of ocular input to subnucleus
      caudalis/upper cervical (Vc/C1) neurons, the orexin-1 receptor antagonist
      SB334867 was applied to the dorsal brainstem surface prior to PH disinhibition,
      by bicuculline methiodide, in male rats under isoflurane anesthesia. Ocular input
      to Vc/C1 units by bright light or hypertonic saline was markedly reduced by PH
      disinhibition and reversed completely by local Vc/C1 application of SB334867. OxA
      applied to the Vc/C1 surface mimicked the effects of PH disinhibition in a dose
      dependent manner. OxA-induced inhibition was prevented by co-application of
      SB334867, but not by the orexin-2 receptor antagonist TCS Ox2 29. PH
      disinhibition and local OxA application also reduced the high threshold
      convergent cutaneous receptive field area of ocular units, suggesting widespread
      effects on somatic input to Vc/C1 ocular units. Vc/C1 application of OxA or
      SB334867 alone did not affect the background discharge of ocular units and
      suggested that the PH-OxA influence on ocular unit activity was not tonically
      active. Vc/C1 application of OxA or SB334867 alone also did not alter mean
      arterial pressure, whereas PH disinhibition evoked prompt and sustained
      increases. These results suggest that stimulus-evoked increases in PH outflow
      acts through OxA and orexin-1 receptors to alter the encoding properties of
      trigeminal brainstem neurons responsive to input from the ocular surface and deep
      tissues of the eye. 

PMID- 24904978
TI  - Plasma amino acids patterns and age of onset of amyotrophic lateral sclerosis.
AB  - The aim of this study was to verify whether abnormalities in plasma amino acid
      (AA) levels could be biological correlates of the age of onset in amyotrophic
      lateral sclerosis (ALS). We undertook plasma AA profiling in a large population
      comprising 117 newly diagnosed ALS patients and 117 matched controls. ALS
      patients were stratified in early (58 patients aged < 55 years) versus late onset
      (59 patients aged > 74 years). We applied a rapid and reproducible method for the
      analysis of AA using amine reactive isotope coded tags in conjunction with liquid
      chromatography coupled to Multiple Reaction Monitoring-Mass Spectrometry. Results
      showed that values of only three AA were significantly different in ALS patients
      and controls. We found lower levels of leucine and higher levels of glutamate and
      leucine in early-onset ALS compared to their matched controls. In conclusion,
      different AA patterns related to the ALS age of onset were found, providing
      insight into possibly aberrant biochemical pathways that might unlock key
      pathological pathways.

PMID- 24904979
TI  - WITHDRAWN: Positive force feedback in development of substrate grip in the stick
      insect tarsus.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.asd.2014.06.002. The duplicate article has therefore
      been withdrawn.

PMID- 24904980
TI  - Calcium signaling and beta2-adrenergic receptors regulate 1-nitropyrene induced
      CXCL8 responses in BEAS-2B cells.
AB  - Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread environmental
      pollutants, generated from reactions between PAHs and nitrogen oxides during
      combustion processes. In the present study we have investigated the mechanisms of
      CXCL8 (IL-8) responses induced by 1-nitropyrene (1-NP) in human bronchial
      epithelial BEAS-2B cells, with focus on the possible importance of Ca(2+)
      signaling and activation of beta2-adrenergic receptors (beta2AR). Ca(2+)-chelator
      treatment obliterated 1-NP-induced CXCL8 (IL-8) responses. 1-NP at 10MUM (but not
      1MUM) induced a rapid and sustained increase in intracellular Ca(2+)-levels
      ([Ca(2+)]i). The early but not the later, sustained phase of 1-NP-induced
      [Ca(2+)]i was suppressed by beta-blocker treatment (carazolol). Moreover,
      inhibition of beta2AR by blocking-antibody, beta-blocker treatment (ICI 118551)
      or siRNA transfection attenuated CXCL8 responses induced by 1-NP. The results
      confirm that PAHs may induce Ca(2+)-signaling also in BEAS-2B cells, at least
      partly through activation of beta2AR, and suggest that both beta2AR- and Ca(2+)
      signaling may be involved in 1-NP-induced CXCL8 responses in bronchial epithelial
      cells. 

PMID- 24904981
TI  - Knowledge of bout duration influences pacing strategies during small-sided games.
AB  - This investigation examines pacing during intermittent team sports. Sixteen
      junior Rugby League players participated in eight different small-sided offside
      touch games. All games were 24 min, but bout durations differed in continuous (1
      * 24 min) or repeated (2 * 12, 3 * 8, 4 * 6, 6 * 4, 8 * 3, 12 * 2 or 24 * 1 min)
      formats. Repeat bouts were interspersed by 2 min of passive rest, and
      participants were informed of the bout duration immediately prior to the game.
      Heart rates, ratings of perceived exertion and data gathered from global
      positioning system devices were used to investigate the pacing strategies
      employed within each game. No significant (P > 0.05) between-game differences
      were observed in total distance; however, during the 1-min bouts, high-speed
      movement was significantly (P < 0.05) increased, during the first and second
      quarters of the 24 * 1-min game compared to all other formats (effect size range:
      0.75 +/- 0.61-1.38 +/- 0.47). Furthermore, the rate of decline in high-speed
      movement over-time was greatest during the 24 * 1-min game with large differences
      observed between the first and third quarters (effect size: 0.90 +/- 0.58).
      Greater moderate-speed (effect size range: 0.62 +/- 0.63-1.56 +/- 0.40) and less
      low-speed (effect size range: 0.69 +/- 0.62-1.54 +/- 0.40) distances were also
      observed during the 1-min bouts, yet heart rates were higher during the
      continuous 1 * 24-min game. Pacing strategies during intermittent activities are
      influenced by the number and duration of exercise bouts. Practitioners should
      consider within-game bout durations when prescribing game-based activities to
      improve aerobic capacity.

PMID- 24904983
TI  - Factors Influencing Break-Time Physical Activity of South African Primary School
      Learners From Low-Income Communities.
AB  - BACKGROUND: The purpose of this study was to assess factors that influence
      physical activity (PA) levels during break-times in South African primary school
      children. METHODS: The System for Observing Play and Leisure Activities in Youth
      (SOPLAY) was used to observe PA levels during break-times at low-income schools
      (4 intervention, 4 control). The intervention was based on action-planning
      including: school environment, curriculum, and family involvement. Categories of
      observed activity included Sedentary, Eating, Walking, or Vigorous PA. Contextual
      factors assessed included teacher supervision, equipment, and crowding. Chi
      square tests were used to determine associations between PA levels and contextual
      factors. RESULTS: In the 970 observations made, 31% of learners were sedentary,
      14% were eating, 29% were walking, and 26% were engaged in vigorous PA. There
      were no differences in break-time PA between intervention and control groups
      (NS). With supervision, children were more likely to eat and less likely to do
      vigorous PA (P = .035). Playground crowding was associated with lower levels of
      vigorous activity and more sedentary behavior (P = .000). CONCLUSIONS: PA during
      break-time was adversely affected by over-crowding and lower with supervision.
      The results suggest that interventions may be targeted at the school policy
      environment to reduce these barriers to PA.

PMID- 24904982
TI  - Effects of in utero exposure of C57BL/6J mice to 2,3,7,8-tetrachlorodibenzo-p
      dioxin on epidermal permeability barrier development and function.
AB  - BACKGROUND: Development of the epidermal permeability barrier (EPB) is essential
      for neonatal life. Defects in this barrier are found in many skin diseases such
      as atopic dermatitis. OBJECTIVE: We investigated the effects of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) on the development and function of the EPB.
      METHODS: Timed-pregnant C57BL/6J mice were gavaged with corn oil or TCDD (10
      MUg/kg body weight) on gestation day 12. Embryos were harvested on embryonic day
      (E) 15, E16, E17, and postnatal day (PND) 1. RESULTS: A skin permeability assay
      showed that TCDD accelerated the development of the EPB, beginning at E15. This
      was accompanied by a significant decrease in transepidermal water loss (TEWL),
      enhanced stratification, and formation of the stratum corneum (SC). The levels of
      several ceramides were significantly increased at E15 and E16. PND1 histology
      revealed TCDD-induced acanthosis and epidermal hyperkeratosis. This was
      accompanied by disrupted epidermal tight junction (TJ) function, with increased
      dye leakage at the terminal claudin-1-staining TJs of the stratum granulosum.
      Because the animals did not have enhanced rates of TEWL, a commonly observed
      phenotype in animals with TJ defects, we performed tape-stripping. Removal of
      most of the SC resulted in a significant increase in TEWL in TCDD-exposed PND1
      pups compared with their control group. CONCLUSIONS: These findings demonstrate
      that in utero exposure to TCDD accelerates the formation of an abnormal EPB with
      leaky TJs, warranting further study of environmental exposures, epithelial TJ
      integrity, and atopic disease.

PMID- 24904984
TI  - Bicycle Commuting and Exposure to Air Pollution: A Questionnaire-Based
      Investigation of Perceptions, Symptoms, and Risk Management Strategies.
AB  - BACKGROUND: An increase in bicycle commuting participation may improve public
      health and traffic congestion in cities. Information on air pollution exposure
      (such as perception, symptoms, and risk management) contributes to the
      responsible promotion of bicycle commuting participation. METHODS: To determine
      perceptions, symptoms, and willingness for specific exposure risk management
      strategies of exposure to air pollution, a questionnaire-based cross-sectional
      investigation was conducted with adult bicycle commuters (n = 153; age = 41 +/-
      11 years; 28% female). RESULTS: Frequency of acute respiratory signs and symptoms
      were positively associated with in-commute and postcommute compared with
      precommute time periods (P < .05); there was greater positive association with
      respiratory disorder compared with healthy, and female compared with male,
      participants. The perception (but not signs or symptoms) of in-commute exposure
      to air pollution was positively associated with the estimated level of in-commute
      proximity to motorized traffic. The majority of participants indicated a
      willingness (which varied with health status and gender) to adopt risk management
      strategies (with desired features) if shown to be appropriate and effective.
      CONCLUSIONS: While acute signs and symptoms of air pollution exposure are
      indicated with bicycle commuting, and more so in susceptible individuals, there
      is willingness to manage exposure risk by adopting effective strategies with
      desired features.

PMID- 24904985
TI  - Effects of protein-ligand interactions on hydrogen/deuterium exchange kinetics:
      canonical and noncanonical scenarios.
AB  - Hydrogen/deuterium exchange (HDX) methods are widely used for monitoring protein
      ligand interactions. This approach relies on the fact that ligand binding can
      modulate the extent of protein structural fluctuations that transiently disrupt
      hydrogen bonds and expose backbone amides to the solvent. It is commonly observed
      that ligand binding causes a reduction of HDX rates. This reduction can be
      restricted to elements adjacent to the binding site, but other regions can be
      affected as well. Qualitatively, ligand-induced HDX protection can be
      rationalized on the basis of two-state models that equate structural dynamics
      with global unfolding/refolding. Unfortunately, such models tend to be
      unrealistic because the dynamics of native proteins are dominated by subglobal
      transitions and local fluctuations. Ligand binding lowers the ground-state free
      energy. It is not obvious why this should necessarily be accompanied by a
      depletion of excited-state occupancies, which would be required for a reduction
      of HDX rates. Here, we propose a framework that implies that ligand binding can
      either slow or accelerate amide deuteration throughout the protein. These
      scenarios are referred to as "type 1" and "type 2", respectively. Evidence for
      type 1 binding is abundant in the literature, whereas the viability of type 2
      interactions is less clear. Using HDX mass spectrometry (MS), we demonstrate that
      the oxygenation of hemoglobin (Hb) provides a dramatic example of a type 2
      scenario. The observed behavior is consistent with cooperative T -> R switching,
      where part of the intrinsic O2 binding energy is reinvested for destabilization
      of the ground state. This destabilization increases the Boltzmann occupancy of
      unfolded conformers, thereby enhancing HDX rates. Surprisingly, O2 binding to
      myoglobin (Mb) also induces elevated HDX rates. These Mb data reveal that type 2
      behavior is not limited to cooperative multisubunit systems. Although enhanced
      protection from deuteration is widely considered to be a hallmark of protein
      ligand interactions, this work establishes that an overall deuteration increase
      also represents a viable outcome. HDX-based ligand screening assays, therefore,
      have to allow for canonical as well as noncanonical effects. 

PMID- 24904986
TI  - An Adaptive Staggered Dose Design for a Normal Endpoint.
AB  - In a clinical trial where several doses are compared to a control, a multi-stage
      design that combines both the selection of the best dose and the confirmation of
      this selected dose is desirable. An example is the two-stage drop-the-losers or
      pick-the-winner design, where inferior doses are dropped after interim analysis.
      Selection of target dose(s) can be based on ranking of observed effects,
      hypothesis testing with adjustment for multiplicity, or other criteria at interim
      stages. A number of methods have been proposed and have made significant gains in
      trial efficiency. However, many of these designs started off with all doses with
      equal allocation and did not consider prioritizing the doses using existing dose
      response information. We propose an adaptive staggered dose procedure that allows
      explicit prioritization of doses and applies error spending scheme that favors
      doses with assumed better responses. This design starts off with only a subset of
      the doses and adaptively adds new doses depending on interim results. Using
      simulation, we have shown that this design performs better in terms of increased
      statistical power than the drop-the-losers design given strong prior information
      of dose response. 

PMID- 24904987
TI  - Messenger RNA (mRNA) nanoparticle tumour vaccination.
AB  - Use of mRNA-based vaccines for tumour immunotherapy has gained increasing
      attention in recent years. A growing number of studies applying nanomedicine
      concepts to mRNA tumour vaccination show that the mRNA delivered in nanoparticle
      format can generate a more robust immune response. Advances in the past decade
      have deepened our understanding of gene delivery barriers, mRNA's biological
      stability and immunological properties, and support the notion for engineering
      innovations tailored towards a more efficient mRNA nanoparticle vaccine delivery
      system. In this review we will first examine the suitability of mRNA for
      engineering manipulations, followed by discussion of a model framework that
      highlights the barriers to a robust anti-tumour immunity mediated by mRNA
      encapsulated in nanoparticles. Finally, by consolidating existing literature on
      mRNA nanoparticle tumour vaccination within the context of this framework, we aim
      to identify bottlenecks that can be addressed by future nanoengineering research.

PMID- 24904988
TI  - Different effects of guanine nucleotides (GDP and GTP) on protein-mediated
      mitochondrial proton leak.
AB  - In this study, we compared the influence of GDP and GTP on isolated mitochondria
      respiring under conditions favoring oxidative phosphorylation (OXPHOS) and under
      conditions excluding this process, i.e., in the presence of carboxyatractyloside,
      an adenine nucleotide translocase inhibitor, and/or oligomycin, an FOF1-ATP
      synthase inhibitor. Using mitochondria isolated from rat kidney and human
      endothelial cells, we found that the action of GDP and GTP can differ
      diametrically depending on the conditions. Namely, under conditions favoring
      OXPHOS, both in the absence and presence of linoleic acid, an activator of
      uncoupling proteins (UCPs), the addition of 1 mM GDP resulted in the state 4 (non
      phosphorylating respiration)-state 3 (phosphorylating respiration) transition,
      which is characteristic of ADP oxidative phosphorylation. In contrast, the
      addition of 1 mM GTP resulted in a decrease in the respiratory rate and an
      increase in the membrane potential, which is characteristic of UCP inhibition.
      The stimulatory effect of GDP, but not GTP, was also observed in inside-out
      submitochondrial particles prepared from rat kidney mitochondria. However, the
      effects of GDP and GTP were more similar in the presence of OXPHOS inhibitors.
      The importance of these observations in connection with the action of UCPs,
      adenine nucleotide translocase (or other carboxyatractyloside-sensitive
      carriers), carboxyatractyloside- and purine nucleotide-insensitive carriers, as
      well as nucleoside-diphosphate kinase (NDPK) are considered. Because the
      measurements favoring oxidative phosphorylation better reflect in vivo
      conditions, our study strongly supports the idea that GDP cannot be considered a
      significant physiological inhibitor of UCP. Moreover, it appears that, under
      native conditions, GTP functions as a more efficient UCP inhibitor than GDP and
      ATP. 

PMID- 24904989
TI  - Implicit theories about intelligence and growth (personal best) goals: Exploring
      reciprocal relationships.
AB  - BACKGROUND: There has been increasing interest in growth approaches to students'
      academic development, including value-added models, modelling of academic
      trajectories, growth motivation orientations, growth mindsets, and growth goals.
      AIMS: This study sought to investigate the relationships between implicit
      theories about intelligence (incremental and entity theories) and growth
      (personal best, PB) goals - with particular interest in the ordering of factors
      across time. SAMPLE: The study focused on longitudinal data of 969 Australian
      high school students. METHOD: The classic cross-lagged panel design (using
      structural equation modelling) was employed to shed light on the ordering of Time
      1 growth goals, incremental theories, and entity theories relative to Time 2 (1
      year later) growth goals, incremental theories, and entity theories. RESULTS:
      Findings showed that Time 1 growth goals predicted Time 2 incremental theories
      (positively) and entity theories (negatively); Time 1 entity and incremental
      theories negatively predicted Time 2 incremental and entity theories
      respectively; but, Time 1 incremental theories and entity theories did not
      predict growth goals at Time 2. CONCLUSION: This suggests that entity and
      incremental theories are negatively reciprocally related across time, but growth
      goals seem to be directionally salient over incremental and entity theories.
      Implications for promoting growth goals and growth mindsets are discussed.

PMID- 24904991
TI  - Effects of social context on feedback-related activity in the human ventral
      striatum.
AB  - It is now well established that activation of the ventral striatum (VS) encodes
      feedback related information, in particular, aspects of feedback validity, reward
      magnitude, and reward probability. More recent findings also point toward a role
      of VS in encoding social context of feedback processing. Here, we investigated
      the effect of social observation on neural correlates of feedback processing. To
      this end, subjects performed a time estimation task and received positive,
      negative, or uninformative feedback. In one half of the experiment subjects
      thought that an experimenter closely monitored their face via a camera. We
      successfully replicated an elevated VS response to positive relative to negative
      feedback. Further, our data demonstrate that this reward-related activation of
      the VS is increased during observation by others. Using uninformative feedback as
      reference condition, we show that specifically VS activation during positive
      feedback was modulated by observation manipulation. Our findings support accounts
      which posit a role of VS in integrating social context into the processing of
      feedback and, in doing so, signaling its social relevance. 

PMID- 24904990
TI  - Serum estradiol levels predict survival and acute kidney injury in patients with
      septic shock--a prospective study.
AB  - Sex hormones have diverse immunomodulatory effects that may be involved in the
      pathogenesis of sepsis. However, the roles of serum sex hormones in predicting
      outcomes and the severity of organ dysfunction, especially acute kidney injury
      (AKI), in septic shock patients remains controversial. We prospectively enrolled
      107 clinically diagnosed pneumonia-related septic shock patients and serum sex
      hormone levels were measured on the day of shock onset. The aim of the present
      study was to investigate the predictive values of serum sex hormones levels for
      28-day mortality and organs dysfunction, especially AKI. Compared with survivors,
      serum levels of progesterone (p<0.001) and estradiol (p<0.001) were significantly
      elevated in non-survivors. In multivariate Cox regression analysis, serum level
      of estradiol >40 pg/mL (p = 0.047) and APACHE II score >=25 (p = <0.001) were
      found to be independent predictors of day 28 mortality. Inclusion of estradiol
      levels further enhanced the ability of APACHE II scores to predict survival in
      patients with high mortality risk. A serum level of estradiol >40 pg/mL was also
      an independent predictor of concomitant AKI (p = 0.002) and correlated well with
      severity of renal dysfunction using RIFLE classification. Elevated serum
      estradiol levels also predicted the development of new AKI within 28 days of
      shock onset (p = 0.013). In conclusion, serum estradiol levels appear to have
      value in predicting 28-day mortality in septic shock patients. Increased serum
      estradiol levels are associated with higher severity of concomitant AKI and
      predict development of new AKI. 

PMID- 24904993
TI  - Self-regulation of inter-hemispheric visual cortex balance through real-time fMRI
      neurofeedback training.
AB  - Recent advances in neurofeedback based on real-time functional magnetic resonance
      imaging (fMRI) allow for learning to control spatially localized brain activity
      in the range of millimeters across the entire brain. Real-time fMRI neurofeedback
      studies have demonstrated the feasibility of self-regulating activation in
      specific areas that are involved in a variety of functions, such as perception,
      motor control, language, and emotional processing. In most of these previous
      studies, participants trained to control activity within one region of interest
      (ROI). In the present study, we extended the neurofeedback approach by now
      training healthy participants to control the interhemispheric balance between
      their left and right visual cortices. This was accomplished by providing feedback
      based on the difference in activity between a target visual ROI and the
      corresponding homologue region in the opposite hemisphere. Eight out of 14
      participants learned to control the differential feedback signal over the course
      of 3 neurofeedback training sessions spread over 3 days, i.e., they produced
      consistent increases in the visual target ROI relative to the opposite visual
      cortex. Those who learned to control the differential feedback signal were
      subsequently also able to exert that control in the absence of neurofeedback.
      Such learning to voluntarily control the balance between cortical areas of the
      two hemispheres might offer promising rehabilitation approaches for neurological
      or psychiatric conditions associated with pathological asymmetries in brain
      activity patterns, such as hemispatial neglect, dyslexia, or mood disorders.

PMID- 24904992
TI  - Interpreting response time effects in functional imaging studies.
AB  - It has been suggested that differential neural activity in imaging studies is
      most informative if it is independent of response time (RT) differences. However,
      others view RT as a behavioural index of key cognitive processes, which is likely
      linked to underlying neural activity. Here, we reconcile these views using the
      effort and engagement framework developed by Taylor, Rastle, and Davis (2013) and
      data from the domain of reading aloud. We propose that differences in neural
      engagement should be independent of RT, whereas, differences in neural effort
      should co-vary with RT. We illustrate these different mechanisms using data from
      an fMRI study of neural activity during reading aloud of regular words, irregular
      words, and pseudowords. In line with our proposals, activation revealed by
      contrasts designed to tap differences in neural engagement (e.g., words are
      meaningful and therefore engage semantic representations more than pseudowords)
      survived correction for RT, whereas activation for contrasts designed to tap
      differences in neural effort (e.g., it is more difficult to generate the
      pronunciation of pseudowords than words) correlated with RT. However, even for
      contrasts designed to tap neural effort, activity remained after factoring out
      the RT-BOLD response correlation. This may reveal unpredicted differences in
      neural engagement (e.g., learning phonological forms for pseudowords>words) that
      could further the development of cognitive models of reading aloud. Our framework
      provides a theoretically well-grounded and easily implemented method for
      analysing and interpreting RT effects in neuroimaging studies of cognitive
      processes. 

PMID- 24904994
TI  - tDCS-induced alterations in GABA concentration within primary motor cortex
      predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy
      study.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive brain
      stimulation technique that alters cortical excitability in a polarity specific
      manner and has been shown to influence learning and memory. tDCS may have both on
      line and after-effects on learning and memory, and the latter are thought to be
      based upon tDCS-induced alterations in neurochemistry and synaptic function. We
      used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with
      a robotic force adaptation and de-adaptation task, to investigate whether tDCS
      induced alterations in GABA and Glutamate within motor cortex predict motor
      learning and memory. Note that adaptation to a robot-induced force field has long
      been considered to be a form of model-based learning that is closely associated
      with the computation and 'supervised' learning of internal 'forward' models
      within the cerebellum. Importantly, previous studies have shown that on-line tDCS
      to the cerebellum, but not to motor cortex, enhances model-based motor learning.
      Here we demonstrate that anodal tDCS delivered to the hand area of the left
      primary motor cortex induces a significant reduction in GABA concentration. This
      effect was specific to GABA, localised to the left motor cortex, and was polarity
      specific insofar as it was not observed following either cathodal or sham
      stimulation. Importantly, we show that the magnitude of tDCS-induced alterations
      in GABA concentration within motor cortex predicts individual differences in both
      motor learning and motor memory on the robotic force adaptation and de-adaptation
      task.

PMID- 24904995
TI  - Indications for intervention during active surveillance of prostate cancer: a
      comparison of the Johns Hopkins and Prostate Cancer Research International Active
      Surveillance (PRIAS) protocols.
AB  - OBJECTIVE: To analyse how patients enrolled in our biopsy based surveillance
      programme would fare under the Prostate Cancer Research International Active
      Surveillance (PRIAS) protocol, which uses PSA kinetics. PATIENTS AND METHODS:
      Since 1995, 1125 men with very-low-risk prostate cancer have enrolled in the AS
      programme at the Johns Hopkins Hospital (JHH), which is based on monitoring with
      annual biopsy. The PRIAS protocol uses a combination of periodic biopsies (in
      years 1, 4, and 7) and prostate-specific antigen doubling time (PSADT) to trigger
      intervention. Patients enrolled in the JHH AS programme were retrospectively
      reviewed to evaluate how the use of the PRIAS protocol would alter the timing and
      use of curative intervention. RESULTS: Over a median of 2.1 years of follow up,
      38% of men in the JHH AS programme had biopsy reclassification. Of those, 62%
      were detected at biopsy intervals corresponding to the PRIAS criteria, while 16%
      were detected between scheduled PRIAS biopsies, resulting in a median delay in
      detection of 1.9 years. Of the 202 men with >5 years of follow-up, 11% in the JHH
      programme were found to have biopsy reclassification after it would have been
      identified in the PRIAS protocol, resulting in a median delay of 4.7 years to
      reclassification. In all, 12% of patients who would have undergone immediate
      intervention under PRIAS due to abnormal PSA kinetics would never have undergone
      reclassification on the JHH protocol and thus would not have undergone definitive
      intervention. CONCLUSIONS: There are clear differences between PSA kinetics-based
      AS programmes and biopsy based programmes. Further studies should address whether
      and how the differences in timing of intervention impact subsequent disease
      progression and prostate cancer mortality.

PMID- 24904996
TI  - Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.
AB  - As the major lysosomal degradation pathway, autophagy represents the guardian of
      cellular homeostasis, removing damaged and potentially harmful material and
      replenishing energy reserves in conditions of starvation. Given its vast
      physiological importance, autophagy is crucially involved in the process of aging
      and associated pathologies. Although the regulation of autophagy strongly depends
      on nutrient availability, specific metabolites that modulate autophagic responses
      are poorly described. Recently, we revealed nucleo-cytosolic acetyl-coenzyme A
      (AcCoA) as a phylogenetically conserved inhibitor of starvation-induced and age
      associated autophagy. AcCoA is the sole acetyl-group donor for protein
      acetylation, explaining why pharmacological or genetic manipulations that modify
      the concentrations of nucleo-cytosolic AcCoA directly affect the levels of
      protein acetylation. The acetylation of histones and cytosolic proteins inversely
      correlates with the rate of autophagy in yeast and mammalian cells, respectively,
      despite the fact that the routes of de novo AcCoA synthesis differ across phyla.
      Thus, we propose nucleo-cytosolic AcCoA to act as a conserved metabolic rheostat,
      linking the cellular metabolic state to the regulation of autophagy via effects
      on protein acetylation. 

PMID- 24904998
TI  - The negations of conjunctions, conditionals, and disjunctions.
AB  - How do reasoners understand and formulate denials of compound assertions, such as
      conjunctions and disjunctions? A theory based on mental models postulates that
      individuals enumerate models of the various possibilities consistent with the
      assertions. It therefore predicts a novel interaction: in affirmations,
      conjunctions, A and B, which refer to one possibility, should be easier to
      understand than disjunctions, A or B, which refer to more than one possibility;
      in denials, conjunctions, not(A and B), which refer to more than one possibility,
      should be harder to understand than disjunctions, not(A or B), which do not.
      Conditionals are ambiguous and they should be of intermediate difficulty.
      Experiment 1 corroborated this trend with a task in which the participants
      selected which possibilities were consistent with assertions, such as: Bob denied
      that he wore a yellow shirt and he wore blue pants on Tuesday. Experiment 2
      likewise showed that participants' own formulations of verbal denials yielded the
      same trend in which denials of conjunctions were harder than denials of
      conditionals, which in turn were harder than denials of disjunctions. 

PMID- 24904997
TI  - Proteomic analysis of bladder cancer indicates Prx-I as a key molecule in BI
      TK/GCV treatment system.
AB  - In order to understand the molecular mechanisms of Bifidobacterium infantis
      thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) treatment system
      which was proven to exhibit sustainable anti-tumor growth activity and induce
      apoptosis in bladder cancer, a proteomic approach of isobaric tags for relative
      and absolute quantification (iTRAQ), followed by liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) was used. 192 down-regulated and 210 up-regulated
      proteins were identified after treatment with BI-TK/GCV system in Sprague-Dawley
      (SD) rats. Western blot analysis and immunohistochemistry analysis confirmed that
      Peroxiredoxin-I (Prx-I) was significantly down-regulated in bladder cancer after
      treatment. Prx-I silencing by transfection of Prx-I shRNA significantly
      suppressed growth, promoted apoptosis and regulated the cell cycle in T24 cells
      and reduced the phospho-NF-kappaB p50 and p65 protein expression which revealed
      the links between Prx-I and NF-kappaB pathway implied by Ingenuity pathway
      analysis (IPA). These findings yield new insights into the therapy of bladder
      cancer, revealing Prx-I as a new therapeutic target and indicating BI-TK/GCV
      system as a prospective therapy by down-regulation of Prx-I through NF-kappaB
      signaling pathway. 

PMID- 24904999
TI  - The locus of the emotional Stroop effect: a study with the PRP paradigm.
AB  - Stimuli that are clearly positive or negative (hence valence-laden stimuli) have
      the potential to interrupt unrelated task processing. A typical example is the
      emotional Stroop effect (ESE) in which responding to a certain task feature
      (e.g., color) is delayed by the presentation of task-irrelevant valent stimuli
      (e.g., negative pictures) compared to valence-neutral stimuli. Here we scrutinize
      which processes are slowed down by irrelevant but valent stimulation. In
      Experiment 1, participants performed in a Psychological Refractory Period (PRP)
      experiment with tone discrimination as Task 1 and color discrimination as Task 2.
      Importantly, colors in Task 2 were accompanied by valent or neutral pictures.
      Valent pictures delayed responding in Task 2 (thus an ESE) and this delay was
      additive to the time interval between tasks. In Experiment 2, task order was
      reversed and the ESE in Task 1 fully propagated to the Task 2 tone
      discrimination. These results imply that irrelevant valence-laden stimulation
      delays capacity-limited processes, and we suggest that this is a late perceptual
      process acting on stimulus categorization. 

PMID- 24905001
TI  - Gastrointestinal symptoms and food/nutrition concerns after the great East Japan
      earthquake in March 2011: survey of evacuees in a temporary shelter.
AB  - On March 11, 2011, a 9.1 magnitude earthquake occurred in the eastern Pacific
      Ocean off the coast of northern Japan. A resulting tsunami struck the Japan
      Pacific coast, causing >20,000 deaths, injuries and missing persons. Survivors'
      post-tsunami health and nutritional status were surveyed one month after the
      disaster in a school shelter in Ishinomaki City. Hyogo College of Medicine's
      disaster relief team observations and survivors' questionnaires were used to
      assess the disaster's effects on survivors' lifestyles and gastrointestinal
      symptoms while residing in temporary shelters. Of 236 disaster evacuees 9-88
      years of age (mean age 52 years), 23% lost weight and 28% reported decreased food
      intake one month after the earthquake. Up to 25% of the participants presented
      with gastrointestinal symptoms, including constipation (10%), appetite loss
      (6.4%), vomiting (6.4%), and nausea (2.1%). Although the victims preferred more
      vegetables (44%) or fruit (33%), most food aid received, such as rice balls or
      bread, was carbohydrate-based, possibly because of easy provision and abundance
      in emergency food pantries. The authors asked the volunteers and the Japan Self
      Defense Forces to provide a more balanced diet, including vegetables and fruit.
      Consumption of imbalanced diets may have caused more gastrointestinal symptoms
      for the survivors. Because of the victims' hesitation to request more balanced
      diets, and because of poorly controlled existing chronic disease and mental
      stress, professional public health providers should assure emergency food
      nutrition after disasters.

PMID- 24905003
TI  - Competitive endogenous RNAs cannot alter microRNA function in vivo.
AB  - In this issue of Molecular Cell, Denzler et al. (2014) report a quantitative
      study of microRNA function in adult mouse liver, suggesting that the natural
      abundance of miRNAs and their binding sites generally excludes the previously
      proposed regulation of miRNAs by competitive endogenous RNAs (ceRNAs).

PMID- 24905002
TI  - Dormancy of cancer cells with suppression of AKT activity contributes to survival
      in chronic hypoxia.
AB  - A hypoxic microenvironment in tumors has been recognized as a cause of malignancy
      or resistance to various cancer therapies. In contrast to recent progress in
      understanding the acute response of cancer cells to hypoxia, the characteristics
      of tumor cells in chronic hypoxia remain elusive. We have identified a pancreatic
      cancer cell line, AsPC-1, that is exceptionally able to survive for weeks under
      1% oxygen conditions while most tested cancer cell lines die after only some days
      under these conditions. In chronic hypoxia, AsPC-1 cells entered a state of
      dormancy characterized by no proliferation, no death, and metabolic suppression.
      They reversibly switched to active status after being placed again in optimal
      culture conditions. ATP turnover, an indicator of energy demand, was markedly
      decreased and accompanied by reduced AKT phosphorylation. Forced activation of
      AKT resulted in increased ATP turnover and massive cell death in vitro and a
      decreased number of dormant cells in vivo. In contrast to most cancer cell lines,
      primary-cultured colorectal cancer cells easily entered the dormant status with
      AKT suppression under hypoxia combined with growth factor-depleted conditions.
      Primary colorectal cancer cells in dormancy were resistant to chemotherapy. Thus,
      the ability to survive in a deteriorated microenvironment by entering into
      dormancy under chronic hypoxia might be a common property among cancer cells.
      Targeting the regulatory mechanism inducing this dormant status could provide a
      new strategy for treating cancer. 

PMID- 24905004
TI  - Regulating microtubules and genome stability via the CUL7/3M syndrome complex and
      CUL9.
AB  - In this issue, two studies from Yue Xiong and colleagues (Li et al., 2014; Yan et
      al., 2014) show that CUL7, OBSL1, and CCDC8, all mutated in 3M short stature
      syndrome, form a centrosomal complex that regulates CUL9 and its substrate
      survivin to link mitosis to cell survival.

PMID- 24905005
TI  - Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug
      resistance.
AB  - The existence of subpopulations of cells in cancers with increased tumor
      initiating capacities and self-renewal potential, often termed "cancer stem
      cells," is a much discussed and key area of cancer biology. Such cellular
      heterogeneity is very important because of its impact on therapy and especially
      states of treatment resistance. A major question is whether there is plasticity
      for evolution of these cell states during tumorigenesis that can involve movement
      between cell populations in a reversible fashion. In this review, we discuss the
      possible role of epigenetic abnormalities as well as genetic alterations in such
      dynamics and in the creation of cellular heterogeneity in cancers of all types. 

PMID- 24905006
TI  - The mechanisms behind the therapeutic activity of BET bromodomain inhibition.
AB  - The bromodomain and extraterminal (BET) protein Brd4 recruits transcriptional
      regulatory complexes to acetylated chromatin. While Brd4 is considered to be a
      general transcriptional regulator, pharmacological inhibition of BET proteins
      shows therapeutic activity in a variety of different pathologies, particularly in
      models of cancer and inflammation. Such effects have been attributed to a
      specific set of downstream target genes whose expression is disproportionately
      sensitive to pharmacological targeting of BET proteins. Emerging evidence links
      the transcriptional consequences of BET inhibition to the association of Brd4
      with enhancer elements, which tend to be involved in lineage-specific gene
      regulation. Furthermore, Brd4 engages in direct regulatory interactions with
      several DNA-binding transcription factors to influence their disease-relevant
      functions. Here we review the current understanding of molecular mechanisms that
      underlie the promising therapeutic effects of BET bromodomain inhibition. 

PMID- 24905008
TI  - Immobilization of volatile and corrosive iodine monochloride (ICl) and I(2)
      reagents in a stable metal-organic framework.
AB  - The major discovery here is a robust and water-stable metal-organic framework
      (MOF) material capable of reversible binding of the volatile and reactive
      molecules of ICl and I2. The immobilization of I2 and ICl, as well as their
      controllable release thus achieved, is to facilitate the wide-ranging
      applications of these volatile species as catalysts and reagents in chemical and
      industrial processes. The framework material TMBP.CuI (hereafter TCuI) can be
      conveniently prepared in quantitative yields by heating CuI and the organic
      linker TMBP (3,3',5,5'-tetramethyl-4,4'-bipyrazol) in acetonitrile. The
      microporous three-dimensional net of TCuI features CuI chains that contribute to
      efficient and reversible binding of ICl and I2 molecules, to result in the
      stoichiometrically well-defined adducts of TCuI.ICl and TCuI.I2, respectively.
      Moreover, the confinement of a volatile compound like ICl within the MOF medium
      provides unique opportunities to enhance its reactivity and selectivity as a
      chemical reagent, as is exemplified by the iodination reactions examined herein.
      With this exemplary study, we intend to stimulate interest in further exploring
      MOFs and other porous media (e.g., porous polymers) for entrapping ICl and other
      volatile reagents (e.g., Br2, SCl2, S2Cl2, and SOCl2) and for potentially novel
      reactivity associated with the porous medium. 

PMID- 24905007
TI  - The genetic and biochemical basis of FANCD2 monoubiquitination.
AB  - Fanconi anaemia (FA) is a cancer predisposition syndrome characterized by
      cellular sensitivity to DNA interstrand crosslinkers. The molecular defect in FA
      is an impaired DNA repair pathway. The critical event in activating this pathway
      is monoubiquitination of FANCD2. In vivo, a multisubunit FA core complex
      catalyzes this step, but its mechanism is unclear. Here, we report purification
      of a native avian FA core complex and biochemical reconstitution of FANCD2
      monoubiquitination. This demonstrates that the catalytic FANCL E3 ligase subunit
      must be embedded within the complex for maximal activity and site specificity. We
      genetically and biochemically define a minimal subcomplex comprising just three
      proteins (FANCB, FANCL, and FAAP100) that functions as the monoubiquitination
      module. Residual FANCD2 monoubiquitination activity is retained in cells
      defective for other FA core complex subunits. This work describes the in vitro
      reconstitution and characterization of this multisubunit monoubiquitin E3 ligase,
      providing key insight into the conserved FA DNA repair pathway.

PMID- 24905009
TI  - Reaction kinetics for the biocatalytic conversion of phenazine-1-carboxylic acid
      to 2-hydroxyphenazine.
AB  - The phenazine derivative 2-hydroxyphenazine (2-OH-PHZ) plays an important role in
      the biocontrol of plant diseases, and exhibits stronger bacteriostatic and
      fungistatic activity than phenazine-1-carboxylic acid (PCA) toward some
      pathogens. PhzO has been shown to be responsible for the conversion of PCA to 2
      OH-PHZ, however the kinetics of the reaction have not been systematically
      studied. Further, the yield of 2-OH-PHZ in fermentation culture is quite low and
      enhancement in our understanding of the reaction kinetics may contribute to
      improvements in large-scale, high-yield production of 2-OH-PHZ for biological
      control and other applications. In this study we confirmed previous reports that
      free PCA is converted to 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the
      action of a single enzyme PhzO, and particularly demonstrate that this reaction
      is dependent on NADP(H) and Fe3+. Fe3+ enhanced the conversion from PCA to 2-OH
      PHZ and 28 degrees C was a optimum temperature for the conversion. However, PCA
      added in excess to the culture inhibited the production of 2-OH-PHZ. 2-OH-PCA was
      extracted and purified from the broth, and it was confirmed that the
      decarboxylation of 2-OH-PCA could occur without the involvement of any enzyme. A
      kinetic analysis of the conversion of 2-OH-PCA to 2-OH-PHZ in the absence of
      enzyme and under different temperatures and pHs in vitro, revealed that the
      conversion followed first-order reaction kinetics. In the fermentation, the
      concentration of 2-OH-PCA increased to about 90 mg/L within a red precipitate
      fraction, as compared to 37 mg/L within the supernatant. The results of this
      study elucidate the reaction kinetics involved in the biosynthesis of 2-OH-PHZ
      and provide insights into in vitro methods to enhance yields of 2-OH-PHZ. 

PMID- 24905011
TI  - Nonstructural protein 5A is incorporated into hepatitis C virus low-density
      particle through interaction with core protein and microtubules during
      intracellular transport.
AB  - Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) serves dual functions
      in viral RNA replication and virus assembly. Here, we demonstrate that HCV
      replication complex along with NS5A and Core protein was transported to the lipid
      droplet (LD) through microtubules, and NS5A-Core complexes were then transported
      from LD through early-to-late endosomes to the plasma membrane via microtubules.
      Further studies by cofractionation analysis and immunoelectron microscopy of the
      released particles showed that NS5A-Core complexes, but not NS4B, were present in
      the low-density fractions, but not in the high-density fractions, of the HCV RNA
      containing virions and associated with the internal virion core. Furthermore,
      exosomal markers CD63 and CD81 were also detected in the low-density fractions,
      but not in the high-density fractions. Overall, our results suggest that HCV NS5A
      is associated with the core of the low-density virus particles which exit the
      cell through a preexisting endosome/exosome pathway and may contribute to HCV
      natural infection. 

PMID- 24905010
TI  - Chromatin structure and replication origins: determinants of chromosome
      replication and nuclear organization.
AB  - The DNA replication program is, in part, determined by the epigenetic landscape
      that governs local chromosome architecture and directs chromosome duplication.
      Replication must coordinate with other biochemical processes occurring
      concomitantly on chromatin, such as transcription and remodeling, to insure
      accurate duplication of both genetic and epigenetic features and to preserve
      genomic stability. The importance of genome architecture and chromatin looping in
      coordinating cellular processes on chromatin is illustrated by two recent sets of
      discoveries. First, chromatin-associated proteins that are not part of the core
      replication machinery were shown to affect the timing of DNA replication. These
      chromatin-associated proteins could be working in concert, or perhaps in
      competition, with the transcriptional machinery and with chromatin modifiers to
      determine the spatial and temporal organization of replication initiation events.
      Second, epigenetic interactions are mediated by DNA sequences that determine
      chromosomal replication. In this review, we summarize recent findings and current
      models linking spatial and temporal regulation of the replication program with
      epigenetic signaling. We discuss these issues in the context of the genome's
      three-dimensional structure with an emphasis on events occurring during the
      initiation of DNA replication. 

PMID- 24905012
TI  - A method to assess adherence in inhaler use through analysis of acoustic
      recordings of inhaler events.
AB  - RATIONALE: Poor adherence to inhaler use can be due to poor temporal and/or
      technique adherence. Up until now there has been no way of reliably tracking both
      these factors in everyday inhaler use. OBJECTIVES: This paper introduces a device
      developed to create time stamped acoustic recordings of an individual's inhaler
      use, in which empirical evidence of temporal and technique adherence in inhaler
      use can be monitored over time. The correlation between clinical outcomes and
      adherence, as determined by this device, was compared for temporal adherence
      alone and combined temporal and technique adherence. FINDINGS: The technology was
      validated by showing that the doses taken matched the number of audio recordings
      (r2 = 0.94, p<0.01). To demonstrate that audio analysis of inhaler use gives
      objective information, in vitro studies were performed. These showed that
      acoustic profiles of inhalations correlated with the peak inspiratory flow rate
      (r2 = 0.97, p<0.01), and that the acoustic energy of exhalations into the inhaler
      was related to the amount of drug removed. Despite training, 16% of participants
      exhaled into the mouthpiece after priming, in >20% of their inhaler events.
      Repeated training reduced this to 7% of participants (p = 0.03). When time of use
      was considered, there was no evidence of a relationship between adherence and
      changes in AQLQ (r2 = 0.2) or PEFR (r2 = 0.2). Combining time and technique the
      rate of adherence was related to changes in AQLQ (r2 = 0.53, p = 0.01) and PEFR
      (r2 = 0.29, p = 0.01). CONCLUSIONS: This study presents a novel method to
      objectively assess how errors in both time and technique of inhaler use impact on
      clinical outcomes. TRIAL REGISTRATION: EudraCT 2011-004149-42.

PMID- 24905016
TI  - PtrBAM1, a beta-amylase-coding gene of Poncirus trifoliata, is a CBF regulon
      member with function in cold tolerance by modulating soluble sugar levels.
AB  - beta-Amylase (BAM) catalyses starch breakdown to generate maltose, which can be
      incorporated into sugar metabolism. However, the role of BAM genes in cold
      tolerance is less characterized. In this study, we report the isolation and
      functional characterization of a chloroplast-localizing BAM-encoding gene PtrBAM1
      from Poncirus trifoliata. PtrBAM1 was induced by cold, dehydration and salt, but
      repressed by maltose. Overexpression of PtrBAM1 in tobacco (Nicotiana nudicaulis)
      increased BAM activity, promoted starch degradation and enhanced the contents of
      maltose and soluble sugars, whereas opposite changes were observed when PtrBAM1
      homolog in lemon (Citrus lemon) was knocked down. The tobacco overexpressing
      lines exhibited enhanced tolerance to cold at chilling or freezing temperatures.
      Under cold stress, higher BAM activity and greater accumulation of maltose and
      soluble sugars were observed in the overexpressing lines when compared with the
      wild-type or empty vector transformants. Bioinformatics analysis demonstrated
      that PtrBAM1 promoter contained a CBF-recognizing element. Yeast one-hybrid assay
      demonstrated that PtrCBF could interact with the promoter fragment containing the
      element. Taken together, these results demonstrate that PtrBAM1 is a member of
      CBF regulon and plays an important role in cold tolerance by modulating the
      levels of soluble sugars acting as osmolytes or antioxidants.

PMID- 24905017
TI  - Age-related spatiotemporal reorganization during response inhibition.
AB  - As a key high-level cognitive function in human beings, response inhibition is
      crucial for adaptive behavior. Previous neuroimaging studies have shown that
      older individuals exhibit greater neural activation than younger individuals
      during response inhibition tasks. This finding has been interpreted within a
      neural compensation framework, in which additional neural resources are recruited
      in response to age-related cognitive decline. Although this interpretation has
      received empirical support, the precise event-related temporal course of this age
      related compensatory neural response remains unexplored. In the present study, we
      conducted source analysis on inhibition-related ERP components (i.e., N2 and P3)
      that were recorded while healthy younger and older adults participated in a
      visual Go/NoGo task. We found that older adults showed increased source current
      densities of the N2 and P3 components than younger adults, which support previous
      hemodynamic findings. Further, such age-related differences in neural activation
      were successfully separated between the N2 and P3 periods by source localization
      analysis. Interestingly, the increased activations in older adults were primarily
      localized to the right precentral and postcentral gyri during the N2 period,
      which shifted to the right dorsolateral prefrontal cortex and the right inferior
      frontal gyrus during the P3 period. Taken together, our results clearly
      illustrate the spatiotemporal dynamics of age-related functional brain
      reorganization, and further specify the exact temporal course at the millisecond
      scale by which age-related compensatory neural responses occur during response
      inhibition. 

PMID- 24905014
TI  - NFAT1 and NFAT3 cooperate with HDAC4 during regulation of alternative splicing of
      PMCA isoforms in PC12 cells.
AB  - BACKGROUND: The bulk of human genes undergo alternative splicing (AS) upon
      response to physiological stimuli. AS is a great source of protein diversity and
      biological processes and is associated with the development of many diseases.
      Pheochromocytoma is a neuroendocrine tumor, characterized by an excessive Ca2+
      dependent secretion of catecholamines. This underlines the importance of balanced
      control of calcium transport via regulation of gene expression pattern, including
      different calcium transport systems, such as plasma membrane Ca2+-ATPases
      (PMCAs), abundantly expressed in pheochromocytoma chromaffin cells (PC12 cells).
      PMCAs are encoded by four genes (Atp2b1, Atp2b2, Atp2b3, Atp2b4), whose
      transcript products undergo alternative splicing giving almost 30 variants.
      RESULTS: In this scientific report, we propose a novel mechanism of regulation of
      PMCA alternative splicing in PC12 cells through cooperation of the nuclear factor
      of activated T-cells (NFAT) and histone deacetylases (HDACs). Luciferase assays
      showed increased activity of NFAT in PC12 cells, which was associated with
      altered expression of PMCA. RT-PCR experiments suggested that inhibition of the
      transcriptional activity of NFAT might result in the rearrangement of PMCA
      splicing variants in PC12 cells. NFAT inhibition led to dominant expression of
      2x/c, 3x/a and 4x/a PMCA variants, while in untreated cells the 2w,z/b,
      3z,x/b,c,e,f, and 4x/b variants were found as well. Furthermore, chromatin
      immunoprecipitation experiments showed that NFAT1-HDAC4 or NFAT3-HDAC4 complexes
      might be involved in regulation of PMCA2x splicing variant generation.
      CONCLUSIONS: We suggest that the influence of NFAT/HDAC on PMCA isoform
      composition might be important for altered dopamine secretion by PC12 cells.

PMID- 24905019
TI  - Lymphatic vessel invasion and lymph node metastasis in patients with clinical
      stage I non-small cell lung cancer.
AB  - BACKGROUND: The aim of this study was to investigate the association between the
      presence of lymphatic vessel invasion (LVI) in primary tumors and lymph node (LN)
      metastasis in clinical stage I non-small cell lung cancer (NSCLC) patients.
      MATERIALS AND METHODS: A total of 76 patients who underwent complete resection
      for clinical stage I adenocarcinoma and squamous cell carcinoma were
      retrospectively examined. RESULTS: Tumors consisted of 51 cases of adenocarcinoma
      and 25 cases of squamous cell carcinoma as determined by histology. LN metastasis
      was detected in 24.4% (19/76) of patients. Factors associated with LN metastasis
      on univariate analysis included LVI (p < 0.001) and increased tumor dimensions (p
      < 0.05). Binary logistic regression analysis showed that the presence of LVI (p <
      0.001) was the only predictor of LN metastasis. CONCLUSION: LVI is significantly
      associated with LN metastasis in patients with clinical stage I NSCLC. These
      findings may be helpful in determining the most appropriate operative strategy
      for patients if preoperative detection of LVI becomes feasible.

PMID- 24905020
TI  - Recent trials in immunosuppression and their consequences for current therapy.
AB  - PURPOSE OF REVIEW: Although the scarcity of clinical trials with de-novo
      immunosuppression has been typical over the last 2 years, several attempts have
      been made in drug conversion, dosing optimization, and bioequivalence. On the
      basis of recent clinical and animal studies, future directions of management and
      treatment are outlined. RECENT FINDINGS: Studies with new tacrolimus formulations
      showed better bioavailability and lower doses, which might translate into less
      toxicity. The long-term results of studies with costimulation blockade confirmed
      their safety and efficacy. Calcineurin inhibitor (CNI)-free regimens based on
      mTOR inhibitors were shown to be associated with increased risk of the humoral
      response. Therefore, ongoing trials are predominantly designed to minimize
      calcineurin inhibitor dose only. Biologics, such as B-cell-specific agents
      (bortezomib and rituximab) and complement inhibitors (eculizumab) used to treat
      antibody-mediated rejection, recurrence of glomerulonephritis, are shifted to
      more preventive applications. The pretransplant quantification of alloreactive
      memory/effector T cell response may help to better stratify a patient's
      immunologic risk and allow for drug minimization. SUMMARY: Despite clinical
      trials with innovative protocols with already established agents, tacrolimus
      based and induction-based protocols have been shown to be the mainstay of
      immunosuppressive regimens. In the future, research aims to focus on biomarker
      driven immunosuppression and cell therapy approaches.

PMID- 24905021
TI  - The effect of ischemia/reperfusion on the kidney graft.
AB  - PURPOSE OF REVIEW: Ischemia/reperfusion injury is an unavoidable companion after
      kidney transplantation and influences short-term as well as long-term graft
      outcome. Clinically ischemia/reperfusion injury is associated with delayed graft
      function, graft rejection, and chronic graft dysfunction. Ischemia/reperfusion
      affects many regulatory systems at the cellular level as well as in the renal
      tissue that eventually result in a distinct inflammatory reaction of the kidney
      graft. RECENT FINDINGS: Underlying factors include energy metabolism, cellular
      changes of the mitochondria and cellular membranes, initiation of different forms
      of cell death-like apoptosis and necrosis together with a recently discovered
      mixed form termed necroptosis. Chemokines and cytokines together with other
      factors promote the inflammatory response leading to activation of the innate
      immune system as well as the adaptive immune system. If the inflammatory reaction
      continues within the graft tissue, a progressive interstitial fibrosis develops
      that impacts long-term graft outcome. SUMMARY: It is of particular importance in
      kidney transplantation to understand the underlying mechanisms and effects of
      ischemia/reperfusion on the graft as this knowledge also opens strategies to
      prevent or treat ischemia/reperfusion injury after transplantation in order to
      improve graft outcome.

PMID- 24905018
TI  - GWAS in a box: statistical and visual analytics of structured associations via
      GenAMap.
AB  - With the continuous improvement in genotyping and molecular phenotyping
      technology and the decreasing typing cost, it is expected that in a few years,
      more and more clinical studies of complex diseases will recruit thousands of
      individuals for pan-omic genetic association analyses. Hence, there is a great
      need for algorithms and software tools that could scale up to the whole omic
      level, integrate different omic data, leverage rich structure information, and be
      easily accessible to non-technical users. We present GenAMap, an interactive
      analytics software platform that 1) automates the execution of principled machine
      learning methods that detect genome- and phenome-wide associations among
      genotypes, gene expression data, and clinical or other macroscopic traits, and 2)
      provides new visualization tools specifically designed to aid in the exploration
      of association mapping results. Algorithmically, GenAMap is based on a new
      paradigm for GWAS and PheWAS analysis, termed structured association mapping,
      which leverages various structures in the omic data. We demonstrate the function
      of GenAMap via a case study of the Brem and Kruglyak yeast dataset, and then
      apply it on a comprehensive eQTL analysis of the NIH heterogeneous stock mice
      dataset and report some interesting findings. GenAMap is available from
      http://sailing.cs.cmu.edu/genamap. 

PMID- 24905022
TI  - Megadose stem cell administration as a route to mixed chimerism.
AB  - PURPOSE OF REVIEW: To discuss recent innovations for the application of
      mismatched haploidentical hematopoietic stem cell transplantation as a means to
      achieve immune tolerance prior to allograft transplantation. We highlight the
      advantages of utilizing novel 'veto' cells, to facilitate induction of mixed
      chimerism, under nonmyeloablative conditioning. RECENT FINDINGS: Haploidentical
      hematopoietic stem cell transplantation has been used for leukemia patients,
      where reduction of graft-versus-host disease risk has been routinely attained by
      depleting grafts of T-cells, and escalated doses of CD34 progenitors (i.e.
      megadose) to overcome graft rejection. These 'megadose' transplants overcome
      rejection through a unique immunoregulatory 'veto' capacity. The importance of
      attaining mixed chimerism for allograft tolerance induction in humans has been
      highlighted by several studies of combined haploidentical hematopoietic stem cell
      transplantation and kidney transplants. However, stable chimerism could only by
      attained by making use of T-cell replete haploidentical hematopoietic stem cell
      transplantation, posing a significant risk for graft-versus-host or other immune
      abnormalities. The use of nonalloreactive 'veto' cells, such as anti-third-party
      central memory CD8 T cells, could potentially overcome this barrier. SUMMARY:
      Achieving stable mixed chimerism after haploidentical hematopoietic stem cell
      transplantation, key to utilizing transplantation as a prelude for organ
      tolerance, may be realized by coadministration of 'veto' cells under current
      nonmyeloablative protocols.

PMID- 24905023
TI  - Control of innate immunological mechanisms as a route to drug minimization.
AB  - PURPOSE OF REVIEW: Much research in transplantation focuses on treatments for
      rejection and induction of tolerance. Recent evidence has shown that initial
      inflammation induced by innate immune effectors after transplantation has a key
      role in modulating adaptive immune responses that cause organ rejection. Here, we
      describe the role of the innate immune system, particularly the complement
      activation pathways, and how they influence adaptive immune responses post
      transplantation and current strategies, which are under development to block
      these innate pathways. RECENT FINDINGS: Anaphylatoxins and their respective
      receptors are proving to be important in T-cell-mediated immunity and make
      attractive targets for therapies designed to promote tolerance in solid organ
      transplantation. Additionally, regulators of complement activation are currently
      being tested in clinical trials, with improvements in drug delivery. SUMMARY:
      Preventing ischaemia-reperfusion injury in transplanted organs significantly
      reduces immune activation and promotes graft survival. Research into the
      mechanisms of complement activation in both native organ ischaemia and
      transplantation models detail emerging roles for complement intermediates that
      can serve as targets for intervention, with the aim of reducing early post
      transplant inflammation, reducing the intensity of immunosuppressive regimens,
      leading to prolonged graft survival.

PMID- 24905025
TI  - Flexible margin kinematics and vortex formation of Aurelia aurita and Robojelly.
AB  - The development of a rowing jellyfish biomimetic robot termed as "Robojelly", has
      led to the discovery of a passive flexible flap located between the flexion point
      and bell margin on the Aurelia aurita. A comparative analysis of biomimetic
      robots showed that the presence of a passive flexible flap results in a
      significant increase in the swimming performance. In this work we further
      investigate this concept by developing varying flap geometries and comparing
      their kinematics with A. aurita. It was shown that the animal flap kinematics can
      be replicated with high fidelity using a passive structure and a flap with curved
      and tapered geometry gave the most biomimetic performance. A method for
      identifying the flap location was established by utilizing the bell curvature and
      the variation of curvature as a function of time. Flaps of constant cross-section
      and varying lengths were incorporated on the Robojelly to conduct a systematic
      study of the starting vortex circulation. Circulation was quantified using
      velocity field measurements obtained from planar Time Resolved Digital Particle
      Image Velocimetry (TRDPIV). The starting vortex circulation was scaled using a
      varying orifice model and a pitching panel model. The varying orifice model which
      has been traditionally considered as the better representation of jellyfish
      propulsion did not appear to capture the scaling of the starting vortex. In
      contrast, the pitching panel representation appeared to better scale the
      governing flow physics and revealed a strong dependence on the flap kinematics
      and geometry. The results suggest that an alternative description should be
      considered for rowing jellyfish propulsion, using a pitching panel method instead
      of the traditional varying orifice model. Finally, the results show the
      importance of incorporating the entire bell geometry as a function of time in
      modeling rowing jellyfish propulsion. 

PMID- 24905024
TI  - Effect of exercise-induced enhancement of the leg-extensor muscle-tendon unit
      capacities on ambulatory mechanics and knee osteoarthritis markers in the
      elderly.
AB  - OBJECTIVE: Leg-extensor muscle weakness could be a key component in knee joint
      degeneration in the elderly because it may result in altered muscular control
      during locomotion influencing the mechanical environment within the joint. This
      work aimed to examine whether an exercise-induced enhancement of the triceps
      surae (TS) and quadriceps femoris (QF) muscle-tendon unit (MTU) capacities would
      affect mechanical and biological markers for knee osteoarthritis in the elderly.
      METHODS: Twelve older women completed a 14-week TS and QF MTU exercise
      intervention, which had already been established as increasing muscle strength
      and tendon stiffness. Locomotion mechanics and serum cartilage oligomeric matrix
      protein (COMP) levels were examined during incline walking. MTU mechanical
      properties were assessed using simultaneously ultrasonography and dynamometry.
      RESULTS: Post exercise intervention, the elderly had higher TS and QF contractile
      strength and tendon-aponeurosis stiffness. Regarding the incline gait task, the
      subjects demonstrated a lower external knee adduction moment and lower knee
      adduction angular impulse during the stance phase post-intervention. Furthermore,
      post-intervention compared to pre-intervention, the elderly showed lower external
      hip adduction moment, but revealed higher plantarflexion pushoff moment. The
      changes in the external knee adduction moment were significantly correlated with
      the improvement in ankle pushoff function. Serum COMP concentration increased in
      response to the 0.5-h incline walking exercise with no differences in the
      magnitude of increment between pre- and post-intervention. CONCLUSIONS: This work
      emphasizes the important role played by the ankle pushoff function in knee joint
      mechanical loading during locomotion, and may justify the inclusion of the TS MTU
      in prevention programs aiming to positively influence specific mechanical markers
      for knee osteoarthritis in the elderly. However, the study was unable to show
      that COMP is amenable to change in the elderly following a 14-week exercise
      intervention and, therefore, the physiological benefit of improved muscle
      function for knee cartilage requires further investigation.

PMID- 24905026
TI  - Singlet oxygen triplet energy transfer-based imaging technology for mapping
      protein-protein proximity in intact cells.
AB  - Many cellular processes are carried out by large protein complexes that can span
      several tens of nanometres. Whereas forster resonance energy transfer has a
      detection range of <10 nm, here we report the theoretical development and
      experimental demonstration of a new fluorescence-imaging technology with a
      detection range of up to several tens of nanometres: singlet oxygen triplet
      energy transfer. We demonstrate that our method confirms the topology of a large
      protein complex in intact cells, which spans from the endoplasmic reticulum to
      the outer mitochondrial membrane and the matrix. This new method is thus suited
      for mapping protein proximity in large protein complexes.

PMID- 24905027
TI  - High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared
      photothermal-triggered drug delivery for effective cancer therapy.
AB  - We report here a simple, high-yield yet low-cost approach to design single-layer
      MoS2 nanosheets with controllable size via an improved oleum treatment
      exfoliation process. By decorating MoS2 nanosheets with chitosan, these
      functionalized MoS2 nanosheets have been developed as a chemotherapeutic drug
      nanocarrier for near-infrared (NIR) photothermal-triggered drug delivery,
      facilitating the combination of chemotherapy and photothermal therapy into one
      system for cancer therapy. Loaded doxorubicin could be controllably released upon
      the photothermal effect induced by 808 nm NIR laser irradiation. In vitro and in
      vivo tumor ablation studies demonstrate a better synergistic therapeutic effect
      of the combined treatment, compared with either chemotherapy or photothermal
      therapy alone. Finally, MoS2 nanosheets can also be used as a promising contrast
      agent in X-ray computed tomography imaging due to the obvious X-ray absorption
      ability of Mo. As a result, the high-throughput oleum treatment exfoliation
      process could be extended for fabricating other 2D nanomaterials, and the NIR
      triggered drug release strategy was encouraging for simultaneous imaging-guided
      cancer theranostic application. 

PMID- 24905029
TI  - Direct assembly of 2-oxazolidinones by chemical fixation of carbon dioxide.
AB  - The reaction of beta- and gamma-haloamines with carbon dioxide to give
      pharmaceutically relevant 2-oxazolidinones and 1,3-dioxazin-2-ones, was found to
      proceed efficiently in the presence of a base and in the absence of catalyst.
      After optimization of reaction conditions, the system was successfully expanded
      to a variety of haloamines, even at multigram scale. The reaction was further
      studied in silico by DFT calculations. 

PMID- 24905031
TI  - Fiberoptic and retrograde intubation in difficult pediatric airway: useful
      suggestions.

PMID- 24905030
TI  - A randomized, phase II study of the anti-insulin-like growth factor receptor type
      1 (IGF-1R) monoclonal antibody robatumumab (SCH 717454) in patients with advanced
      colorectal cancer.
AB  - Overexpression of insulin-like growth factor receptor type 1 (IGF-1R) may promote
      tumor development and progression in some cancer patients. Our objective was to
      assess tumor uptake of fluorodeoxyglucose by positron-emission tomography in
      patients with chemotherapy-refractory colorectal cancer treated with an anti
      insulin-like growth factor receptor type 1 (anti-IGF-1R) monoclonal antibody,
      robatumumab. This was a randomized, open-label study with two periods (P1 and
      P2). Patients were randomized 3:1 into treatment arms R/R and C/R that received,
      respectively, one cycle of 0.3 mg/kg robatumumab or one or more cycles of second
      line chemotherapy in P1, followed in either case by 10 mg/kg robatumumab biweekly
      in P2. The primary measure of fluorodeoxyglucose uptake was maximum standardized
      uptake value (SUV(max)). The primary endpoint was the proportion of patients in
      the R/R arm having a mean percent decrease from baseline in SUV(max) (DiSUV)
      greater than 20% 12-14 days postdose in P2. Secondary endpoints included Response
      Evaluation Criteria in Solid Tumors (RECIST)-defined tumor response and
      pharmacodynamic measures of target engagement. Among 41 patients who were
      evaluable for the primary endpoint, seven (17%, 95% CI 7%-32%) had DiSUV greater
      than 20%. Fifty robatumumab-treated patients were evaluable for RECIST-defined
      tumor response and six (12%) had stable disease lasting greater than or equal to
      7 weeks in P2. Pharmacodynamic endpoints indicated target engagement after dosing
      with 10 mg/kg robatumumab, but not 0.3 mg/kg. The most frequently reported
      adverse events were fatigue/asthenia, nausea, anorexia, and gastrointestinal
      disturbances. In this study, few patients with chemotherapy-refractory colorectal
      cancer appeared to benefit from treatment with the IGF-1R antagonist robatumumab.

PMID- 24905032
TI  - Pneumocephalus after epidural anesthesia in an adult who has undergone lumbar
      laminectomy.

PMID- 24905033
TI  - Pulsed radiofrequency for the suprascapular nerve for patients with chronic
      headache.

PMID- 24905034
TI  - Pulsed radiofrequency for the suprascapular nerve for patients with chronic
      headache.

PMID- 24905035
TI  - Hypotension artifact with somatosensory-evoked potential monitoring.

PMID- 24905036
TI  - Ideal blood pressure management and our specialty.

PMID- 24905037
TI  - Therapeutic potential of metformin in papillary thyroid cancer in vitro and in
      vivo.
AB  - Metformin, an anti-diabetic drug used in type 2 diabetes treatment, is reported
      to have oncopreventive or therapeutic roles in several human cancers. The present
      study investigated the therapeutic potential of physiologic dose of metformin in
      PTC. Metformin inhibited PTC cell viability and increased cell apoptosis in
      various doses (0.5-20mM) in BCPAP and BHP10-3SC cells. Western blot analysis
      demonstrated that the p-AMPK/AMPK ratio increased with increased metformin
      treatment. The ectopic tumor experiment was performed using BHP10-3SC cells and
      athymic nude mice. Oral metformin treatment via drinking water significantly
      delayed tumor growth in both tumor development model and established tumor
      models. Necrotic area in tumors significantly increased with metformin treatment.
      Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions
      of mTOR and Akt expressions in metformin-treated mice compared to the results in
      mock-treated control mice. Our results indicate that a physiologic dose of
      metformin has anti-tumorigenic effects that result from activation of AMPK
      signaling and inhibition of Akt signaling.

PMID- 24905039
TI  - Deriving a CO2-permselective carbon membrane from a multilayered matrix of
      polyion complexes.
AB  - A multilayered assembly consisting of polyion complexes was developed over porous
      ceramic as a unique precursor for a carbon membrane (CM). This specific layer was
      attained through in situ polymerization of N-methylpyrrole (mPy) over a prime
      coating layer of poly(4-styrenesulfonic acid) (PSSA) with an embedded oxidant on
      the ceramic surface. Extensive ion-pair complexation between the sulfonic acid
      groups of PSSA and the tertiary amine groups of the resulting poly(N
      methylpyrrole) (PmPy) sustains this assembly layer. Incorporating
      cetyltrimethylammonium bromide (CTAB) into the PSSA is critical in facilitating
      the infiltration of mPy into the PSSA layer and promoting interfacial contact
      between the two polymers. Upon pyrolysis, the precursor coating was collectively
      converted into a carbon composite matrix. Such copyrolysis restrains the grain
      sizes of the carbonized PmPy, thereby halting defects in the resultant
      carbonaceous matrix. The gas separation performances of the CMs obtained at
      various graphitization temperatures showed that the least graphitized carbon
      matrix exhibited the best selectivity of CO2/CH4 = 167 with a CO2 permeability of
      7.19 Barrer. This specific feature is attributed to both imine and imide pendant
      groups that function as selective adsorption sites for CO2 in the carbon
      skeleton. 

PMID- 24905040
TI  - Obstetric triage: a systematic review of the past fifteen years: 1998-2013.
AB  - BACKGROUND: Triage concepts have shifted the focus of obstetric care to include
      obstetric triage units. The purpose of this systematic review is to examine the
      literature on use of triage concepts in obstetrics during a 15-year time frame.
      METHODS: A systematic review was completed of the obstetric triage literature
      from 1998 to 2013 using the electronic online databases from PubMed, CINHAL,
      Ovid, and Cochrane Library Reviews within the English language. Reference lists
      of articles were reviewed to identify other pertinent publications. Both peer
      reviewed and non-peer-reviewed documents were used. INCLUSION CRITERIA: articles
      specifically related to obstetric triage or obstetric emergency practices in the
      hospital setting. Exclusion criteria included: manuscripts that focused on
      general, nonobstetric emergency and triage units, telephone triage, out-of
      hospital practices, other clinical conditions, and references outside the time
      frame of 1998-2013. RESULTS: Key categories were identified: legal issues and
      impact of Emergency Medical Treatment and Active Labor Act (EMTALA); liability
      pitfalls; risk stratification (acuity tools); clinical decision aids;
      utilization, patient flow, and patient satisfaction; impact on interprofessional
      education and advanced nursing practice; and management of selected clinical
      conditions. Components of a best practice model for obstetric triage are
      introduced. CONCLUSION: Seven key triage categories from the literature were
      identified and best practices were developed for obstetric triage units from this
      systematic review. Both can be used to guide future practice and research within
      obstetric triage.

PMID- 24905041
TI  - The catalytic pyrolysis of food waste by microwave heating.
AB  - This study describes a series of experiments that tested the use of microwave
      pyrolysis for treating food waste. Characteristics including rise in temperature,
      and the three-phase products, were analyzed at different microwave power levels,
      after adding 5% (mass basis) metal oxides and chloride salts to the food waste.
      Results indicated that, the metal oxides MgO, Fe2O3 and MnO2 and the chloride
      salts CuCl2 and NaCl can lower the yield of bio-oil and enhance the yield of gas.
      Meanwhile, the metal oxides MgO and MnO2 can also lower the low heating value
      (LHV) of solid residues and increase the pH values of the lower layer bio-oils.
      However, the chloride salts CuCl2 and NaCl had the opposite effects. The optimal
      microwave power for treating food waste was 400W; among the tested catalysts,
      CuCl2 was the best catalyst and had the largest energy ratio of production to
      consumption (ERPC), followed by MnO2.

PMID- 24905038
TI  - Epigenomics of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a large and growing public health problem. It is
      characterized by the accumulation of amyloid beta peptides and abnormally
      phosphorylated tau proteins that are associated with cognitive decline and
      dementia. Much has been learned about the genomics of AD from linkage analyses
      and, more recently, genome-wide association studies. Several but not all aspects
      of the genomic landscape are involved in amyloid beta metabolism. The moderate
      concordance of disease among twins suggests other factors, potentially epigenomic
      factors, are related to AD. We are at the earliest stages of examining the
      relation of the epigenome to the clinical and pathologic phenotypes that
      characterize AD. Our literature review suggests that there is some evidence of
      age-related changes in human brain methylation. Unfortunately, studies of AD have
      been relatively small with limited coverage of methylation sites and microRNA,
      let alone other epigenomic marks. We are in the midst of 2 large studies of human
      brains including coverage of more than 420,000 autosomal cytosine-guanine
      dinucleotides with the Illumina Infinium HumanMethylation450 BeadArray, and
      histone acetylation with chromatin immunoprecipitation sequencing. We present
      descriptive data to help inform other researchers what to expect from these
      approaches to better design and power their studies. We then discuss future
      directions to inform on the epigenomic architecture of AD. 

PMID- 24905042
TI  - Biodiesel production from wet municipal sludge: evaluation of in situ
      transesterification using xylene as a cosolvent.
AB  - This study proposes a method to produce biodiesel from wet wastewater sludge.
      Xylene was used as an alternative cosolvent to hexane for transesterification in
      order to enhance the biodiesel yield from wet wastewater sludge. The water
      present in the sludge could be separated during transesterification by employing
      xylene, which has a higher boiling point than water. Xylene enhanced the
      biodiesel yield up to 8.12%, which was 2.5 times higher than hexane. It was
      comparable to the maximum biodiesel yield of 9.68% obtained from dried sludge.
      Xylene could reduce either the reaction time or methanol consumption, when
      compared to hexane for a similar yield. The fatty acid methyl esters (FAMEs)
      content of the biodiesel increased approximately two fold by changing the
      cosolvent from hexane to xylene. The transesterification method using xylene as a
      cosolvent can be applied effectively and economically for biodiesel recovery from
      wet wastewater sludge without drying process. 

PMID- 24905043
TI  - Rapid cultivation of aerobic granular sludge in a pilot scale sequencing batch
      reactor.
AB  - Aerobic granular sludge which had good performance to pollutants removal was
      successfully cultivated within 18 days in a pilot scale sequencing batch reactor,
      about 25% mature aerobic granular sludge was inoculated when the setting time of
      activated sludge was reduced to 10 min. Anaerobic biological selector was
      implemented to inhibit filamentous bacteria overgrowth, where the maximum COD
      could reach to 1703.74 mg/L. The cultivated aerobic granular sludge was irregular
      and pale yellow, average particle size, SVI, SV30/SV5, PN/PS, EPS and water
      content were 1.58 mm, 67.64 mL/g, 0.91, 2.17, 268.90 mg EPS/g MLVSS and 98.16% on
      the 18th day. Mechanism of rapid granulation mainly included crystal nucleus
      hypothesis and selection pressure hypothesis. The inoculated aerobic granules
      could maintain stable under short setting time environment, making it directly as
      the crystal nucleus and the carriers for new particles without obvious
      disintegration, which eventually shortened the granulation time greatly.

PMID- 24905044
TI  - Metabolic engineering of Escherichia coli for improving shikimate synthesis from
      glucose.
AB  - Shikimate is a key intermediate for the synthesis of the neuraminidase
      inhibitors. Microbial production of shikimate and related derivatives has the
      benefit of cost reduction when compared to traditional methods. In this study, an
      overproducing shikimate Escherichia coli strain was developed by rationally
      engineering certain metabolic pathways. To achieve this, the shikimate pathway
      was blocked by deletion of shikimate kinases and quinic acid/shikimate
      dehydrogenase. EIICB(glc) protein involved in the phosphotransferase system, and
      acetic acid pathway were also removed to increase the amount of available
      phosphoenolpyruvate and decrease byproduct formation, respectively. Thereafter,
      three critical enzymes of mutated 3-deoxy-D-arabinoheptulosonate-7-phosphate
      (DAHP) synthase (encoded by aroG(fbr)), PEP synthase (encoded by ppsA), and
      transketolase A (encoded by tktA) were modularly overexpressed and the resulting
      recombinant strain produced 1207 mg/L shikimate in shake flask cultures. Using
      the fed-batch process, 14.6g/L shikimate with a yield of 0.29 g/g glucose was
      generated in a 7-L bioreactor.

PMID- 24905045
TI  - Bioremediation of coking wastewater containing carbazole, dibenzofuran and
      dibenzothiophene by immobilized naphthalene-cultivated Arthrobacter sp. W1 in
      magnetic gellan gum.
AB  - In this study, the cometabolic degradation of carbazole (CA), dibenzofuran (DBF),
      and dibenzothiophene (DBT) by immobilized Arthrobacter sp. W1 cells pregrown with
      naphthalene was investigated. Four kinds of polymers were evaluated as
      immobilization supports for strain W1. After comparison with agar, alginate, and
      kappa-carrageenan, gellan gum was selected as the optimal immobilization support.
      Furthermore, magnetic Fe3O4 nanoparticle was selected as most suitable
      nanoparticle for immobilization and the optimal concentration was 80 mg/L. The
      relationship between specific degradation rate and the initial concentration of
      CA, DBF and DBT was described well by Michaelis-Menten kinetics. The recycling
      experiments demonstrated that the magnetically immobilized cells coupling with
      activation zeolite showed highly bioremediation activity on the coking wastewater
      containing high concentration of phenol, naphthalene, CA, DBF and DBT during
      seven recycles. Toxicity assessment indicated the treatment of the coking
      wastewater by magnetically immobilized cells with activation zeolite led to less
      toxicity than untreated wastewater.

PMID- 24905046
TI  - Determination of methylene blue biosorption by Rhizopus arrhizus in the presence
      of surfactants with different chemical structures.
AB  - Methylene blue (MB) biosorption properties of Rhizopus arrhizus were investigated
      in the presence of surfactants. The effects of cationic and anionic surfactants
      on MB removal by dead biomass (1 g L(-1)) were determined. MB removal was tested
      as a function of initial pH (2-12), contact time (5-1440 min), and dye (37.4
      944.7 mg L(-1)) and surfactant (0-10 mM) concentrations. The opposite charged
      anionic surfactant dodecylbenzenesulfonic acid sodium salt (DBS) enhanced
      sorption of cationic MB by biomass dramatically. Maximum biosorption capacity was
      471.5 mg g(-1) at pH 8 with 0.5 mM DBS at 944.7 mg L(-1) MB concentration. The
      surfactant-stimulated fungal decolorization method may provide a highly
      efficient, inexpensive, and time-saving procedure in biological wastewater
      treatment technologies.

PMID- 24905047
TI  - Efficient proteolysis and application of an alkaline protease from halophilic
      Bacillus sp. EMB9.
AB  - A salt-stable alkaline protease from moderately halophilic Bacillus sp. EMB9,
      isolated from the western coast of India, is described. This protease was capable
      of efficiently removing silver from used/waste X-Ray films, as well as
      hydrolyzing defatted soy flour with 31% degree of hydrolysis (DH). Production of
      the protease was optimized by using response surface methodology. Ca(2+) and NaCl
      were the most critical factors in enhancing the yield. Under optimized culture
      conditions, a maximum of 369 U protease/mL was obtained, which is quite
      comparable to the yields of commercial proteases. The elevated production level
      coupled with ability to efficiently hydrolyze protein-laden soy flour and
      complete recovery of silver from used X-Ray films makes it a prospective
      industrial enzyme.

PMID- 24905048
TI  - Ultrasonic-assisted production of antioxidative polysaccharides from Crassostrea
      hongkongensis.
AB  - The beneficial effects of oyster extract against various disorders and diseases
      induced by oxidative stress have aroused great interest. In this article,
      ultrasonic-assisted enzymolysis was employed to produce polysaccharides of
      Crassostrea hongkongensis (CHP) and their antioxidant activity was investigated.
      A single-factor experiment and then a four-factor, three-level Box-Behnken design
      were first used to optimize ultrasonic extraction for polysaccharides. On the
      basis of ridge analysis, the optimum conditions are obtained as ultrasonic
      treatment time of 24 min, power of 876 W, temperature of 49 degrees C, and
      material-solvent ratio of 1:6 (w/v). It is found that ultrasound pretreatment
      before protease hydrolysis was a great help to improve CHP yield and purity,
      especially more favorable with flavorzyme, neutrase, alcalase, and pepsin.
      Furthermore, the polysaccharide fraction, which was obtained by ultrasonic
      pretreatment and then alcalase hydrolysis at the conditions of 3000 U/g, 55
      degrees C, pH 8.0, for 4 hr, exhibited an obvious scavenging effect on 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (98.48 +/- 0.55% and 99.20
      +/- 0.12%, respectively) and a lenoleic acid peroxidation inhibition effect
      (85.48 +/- 0.65%) at a concentration of 5.0 mg/mL. These results reveal the
      potential application of CHP in functional food and nutraceuticals.

PMID- 24905049
TI  - Purification and properties of detergent-compatible extracellular alkaline
      protease from Scopulariopsis spp.
AB  - A fungal alkaline protease of Scopulariopsis spp. was purified to homogeneity
      with a recovery of 32.2% and 138.1 U/mg specific activity on lectin-agarose
      column. The apparent molecular mass was 15 +/- 1 kD by sodium dodecyl sulfate
      polyacryalamide gel electrophoresis (SDS-PAGE). It was a homogenous monomeric
      glycoprotein as shown by a single band and confirmed by native PAGE and gelatin
      zymography. The enzyme was active and stable over pH range 8.0-12.0 with optimum
      activity at pH 9.0. The maximum activity was recorded at 50 degrees C and
      remained unaltered at 50 degrees C for 24 hr. The enzyme was stimulated by Co(2+)
      and Mn(2+) at 10 mM but was unaffected by Ba(2+), Mg(2+), Cu(2+), Na(+), K(+),
      and Fe(2+). Ca(2+) and Fe(3+) moderately reduced the activity (~18%); however, a
      reduction of about 40% was seen for Zn(2+) and Hg(2+). The enzyme activity was
      completely inhibited by 5 mM phenylmethylsulfonyl fluoride (PMSF) and partially
      by N-bromosuccinimide (NBS) and tocylchloride methylketone (TLCK). The serine,
      tryptophan, and histidine may therefore be at or near the active site of the
      enzyme. The protease was more active against gelatin compared to casein,
      fibrinogen, egg albumin, and bovine serum albumin (BSA). With casein as
      substrate, Km and Vmax were 4.3 mg/mL and 15.9 U/mL, respectively. An activation
      was observed with sodium dodecyl sulfate (SDS), Tween-80, and Triton X-100 at 2%
      (v/v); however, H2O2 and NaClO did not affect the protease activity. Storage
      stability was better for all the temperatures tested (-20, 4, and 28 +/- 2
      degrees C) with a retention of more than 85% of initial activity after 40 days.
      The protease retained more than 50% activity after 24 hr of incubation at 28, 60,
      and 90 degrees C in the presence (0.7%, w/v) of commercial enzymatic and
      nonenzymatic detergents. The Super Wheel-enzyme solution was able to completely
      remove blood staining, differing from the detergent solution alone. The stability
      at alkaline pH and high temperatures, broad substrate specificity, stability in
      the presence of surfactants and oxidizing and bleaching agents, and excellent
      compatibility with detergents clearly suggested the use of the enzyme in
      detergent formulations.

PMID- 24905050
TI  - A phenolic acid phenethyl urea derivative protects against irradiation-induced
      osteoblast damage by modulating intracellular redox state.
AB  - Because irradiation may cause osteoradionecrosis, antioxidant supplementation is
      often used to suppress irradiation-mediated injury. This study examined whether a
      synthetic phenethyl urea compound, (E)-1-(3,4-dihydroxyphenethyl)-3-(3,4
      dihydroxystyryl)urea (DPDS-U), prevents irradiation-mediated cellular damage in
      MC3T3-E1 osteoblastic cells. A relatively high dose of irradiation (>4 Gy)
      decreased cell viability and proliferation and induced DNA damage and cell cycle
      arrest at the G(2)/M phase with the attendant increase of cyclin B1. Irradiation
      with 8 Gy induced intracellular reactive oxygen species (ROS) production and
      lipid peroxidation, and reduced glutathione content and superoxide dismutase
      activity in the cells. These events were significantly suppressed by treatment
      with 200 uM DPDS-U or 5 mM N-acetyl cysteine (NAC). DPDS-U or irradiation alone
      significantly increased heme oxygenase-1 (HO-1) expression and nuclear factor E2
      p45-related factor-2 (Nrf2) nuclear translocation. Interestingly, pretreatment
      with DPDS-U facilitated irradiation-induced activation of the Nrf2/HO-1 pathway.
      The potential of DPDS-U to mediate HO-1 induction and protect against irradiation
      mediated cellular damage was almost completely attenuated by transient
      transfection with Nrf2-specific siRNA or treatment with a pharmacological HO-1
      inhibitor, zinc protoporphyrin IX. Additional experiments revealed that DPDS-U
      induced a radioprotective mechanism that differs from that induced by NAC through
      activation of Nrf2/HO-1 signaling. Collectively, our data suggest that DPDS-U
      induced radioprotection is due to its dual function as an antioxidant to remove
      directly excessive intracellular ROS and as a prooxidant to stimulate
      intracellular redox-sensitive survival signal.

PMID- 24905051
TI  - Synthesis, structure, and peculiar green emission of NaBaBO3:Ce3+ phosphors.
AB  - Polycrystalline samples of Ce(3+)-doped NaBaBO3 (0.5-15 mol%) were prepared by
      the solid-phase synthesis. The phase formation was confirmed by X-ray powder
      diffraction (XRD) measurements and structural refinement. The photoluminescence
      excitation and emission spectra and decay curves were measured. The absolute
      luminescence quantum efficiency (QE) and the activation energy (DeltaE) were
      reported. Under the excitation of near-UV light, Ce(3+)-doped NaBaBO3 presents a
      green-emission band centred at 505 nm from the allowed inter-configurational 4f
      5d transition. The maximum absolute QE of NaBaBO3:Ce(3+) was measured to be 58%
      excited with 395 nm light at 300 K. The thermal stability of the green
      luminescence was evaluated by the luminescence decays as a function of
      temperature. The phosphor shows an excellent thermal stability on temperature
      quenching effects. Compared with the reported Ce(3+)-doped alkali metal and
      alkaline earth orthoborates with the general formula MNBO3 with only blue
      luminescence, the peculiarity of NaBaBO3:Ce(3+) is the green emission and a high
      doping concentration in the lattices. The results were discussed on the
      relationship between the structure and the luminescence properties. 

PMID- 24905052
TI  - Distribution and histopathological changes induced by cysts of Taenia solium in
      the brain of pigs from Tanzania.
AB  - Neurocysticercosis (NCC) caused by Taenia solium cysts is a frequent but
      neglected parasitic disease of the central nervous system (CNS) worldwide. The
      aim of this study was to describe anatomical locations of cysts in the CNS and
      the corresponding inflammation. A total of 17 naturally infected pigs were used
      to evaluate the distribution of cysts and, of these, seven were used to evaluate
      the corresponding inflammation further, through histopathology. Clinical signs in
      the pigs included dullness, sluggishness, somnolence, apathy and loss of
      consciousness. Cysts were distributed in all cerebral lobes, i.e. 39.7% in the
      frontal lobe, 20.3% in the parietal lobe, 20.0% in the occipital lobe and 19.7%
      in the temporal lobe, and only 0.4% in the cerebellum. No cysts were found in the
      spinal cord. Cysts were localized as follows: 47.9% in the dorsal subarachnoid,
      46.9% in the parenchyma, 4.4% in the subarachnoid base and 0.9% in the
      ventricles. The results of the histopathology revealed lesions in an early
      inflammatory stage, i.e. stage I, in all anatomical locations except for two,
      which showed more of an inflammatory reaction, stage III, in one pig. It was
      concluded that clinical signs in pigs were neither pathognomonic nor consistent.
      These signs, therefore, cannot be used as a reliable indicator of porcine NCC.
      Furthermore, T. solium cysts were found to be in abundance in all cerebral lobes,
      and only a few were found in the cerebellum. Regarding the inflammatory response,
      no significant differences were found in the location and total number of cysts.
      Thus, further studies are needed to explain the determinants of cyst distribution
      in the CNS and assess in detail clinical signs associated with porcine NCC.

PMID- 24905053
TI  - Graphitic nanostripes in silicon carbide surfaces created by swift heavy ion
      irradiation.
AB  - The controlled creation of defects in silicon carbide represents a major
      challenge. A well-known and efficient tool for defect creation in dielectric
      materials is the irradiation with swift (E(kin) >= 500 keV/amu) heavy ions, which
      deposit a significant amount of their kinetic energy into the electronic system.
      However, in the case of silicon carbide, a significant defect creation by
      individual ions could hitherto not be achieved. Here we present experimental
      evidence that silicon carbide surfaces can be modified by individual swift heavy
      ions with an energy well below the proposed threshold if the irradiation takes
      place under oblique angles. Depending on the angle of incidence, these grooves
      can span several hundreds of nanometres. We show that our experimental data are
      fully compatible with the assumption that each ion induces the sublimation of
      silicon atoms along its trajectory, resulting in narrow graphitic grooves in the
      silicon carbide matrix.

PMID- 24905054
TI  - Factors That Influence Park Use and Physical Activity in Predominantly Hispanic
      and Low-Income Neighborhoods.
AB  - BACKGROUND: Park features' association with physical activity among predominantly
      Hispanic communities is not extensively researched. The purpose of this study was
      to assess factors associated with park use and physical activity among park users
      in predominantly Hispanic neighborhoods. METHODS: Data were collected across 6
      parks and included park environmental assessments to evaluate park features,
      physical activity observations to estimate physical activity energy expenditure
      as kcal/kg/ minute per person, and park user interviews to assess motivators for
      park use. Quantitative data analysis included independent t tests and ANOVA.
      Thematic analysis of park user interviews was conducted collectively and by
      parks. RESULTS: Parks that were renovated had higher physical activity energy
      expenditure scores (mean = .086 +/- .027) than nonrenovated parks (mean = .077 +/
      .028; t = -3.804; P < .01). Basketball courts had a significantly higher number
      of vigorously active park users (mean = 1.84 +/- .08) than tennis courts (mean =
      .15 +/- .01; F = 21.9, eta(2) = 6.1%, P < .01). Thematic analysis of qualitative
      data revealed 4 emerging themes-motivation to be physically active, using the
      play spaces in the park, parks as the main place for physical activity, and
      social support for using parks. CONCLUSION: Renovations to park amenities, such
      as increasing basketball courts and trail availability, could potentially
      increase physical activity among low-socioeconomic-status populations.

PMID- 24905055
TI  - Waist-Worn Actigraphy: Population-Referenced Percentiles for Total Activity
      Counts in U.S. Adults.
AB  - BACKGROUND: Accelerometer-derived total activity count is a measure of total
      physical activity (PA) volume. The purpose of this study was to develop age- and
      gender-specific percentiles for daily total activity counts (TAC), minutes of
      moderate-to-vigorous physical activity (MVPA), and minutes of light physical
      activity (LPA) in U.S. adults. METHODS: Waist-worn accelerometer data from the
      2003-2006 National Health and Nutrition Examination Survey were used for this
      analysis. The sample included adults >= 20 years with >= 10 hours accelerometer
      wear time on >= 4 days (N = 6093). MVPA and LPA were defined as the number of 1
      minute epochs with counts >= 2020 and 100 to 2019, respectively. TAC represented
      the activity counts acquired daily. TAC, MVPA, and LPA were averaged across valid
      days to produce a daily mean. RESULTS: Males in the 50th percentile accumulated
      288 140 TAC/day, with 357 and 22 minutes/day spent in LPA and MVPA, respectively.
      The median for females was 235 741 TAC/ day, with 349 and 12 minutes/day spent in
      LPA and MVPA, respectively. CONCLUSIONS: Population-referenced TAC percentiles
      reflect the total volume of PA, expressed relative to other adults. This is a
      different approach to accelerometer data reduction that complements the current
      method of looking at time spent in intensity subcategories.

PMID- 24905056
TI  - Simulation-based study comparing multiple imputation methods for non-monotone
      missing ordinal data in longitudinal settings.
AB  - The application of multiple imputation (MI) techniques as a preliminary step to
      handle missing values in data analysis is well established. The MI method can be
      classified into two broad classes, the joint modeling and the fully conditional
      specification approaches. Their relative performance for the longitudinal ordinal
      data setting under the missing at random (MAR) assumption is not well documented.
      This article intends to fill this gap by conducting a large simulation study on
      the estimation of the parameters of a longitudinal proportional odds model. The
      two MI methods are also illustrated in quality of life data from a cancer
      clinical trial. 

PMID- 24905057
TI  - Protecting our Khmer daughters: ghosts of the past, uncertain futures, and the
      human papillomavirus vaccine.
AB  - OBJECTIVES: The FDA approved the first human papillomavirus (HPV) vaccine in
      2006. Research into parental decision-making and concerns about HPV vaccination
      highlights questions about parenting and parents' role in the crafting of their
      daughters' future sexuality. In contrast to much of this literature, we explore
      narratives from interviews with Cambodian mothers of HPV vaccine-age eligible
      daughters who experienced genocide and came to the USA as refugees. DESIGN: We
      conducted in-depth, in-person interviews with 25 Cambodian mothers of HPV vaccine
      age eligible daughters. Interviews were conducted in Khmer and translated into
      English for analysis. We followed standard qualitative analysis techniques
      including iterative data review, multiple coders, and 'member checking.' Five
      members of the research team reviewed all transcripts and two members
      independently coded each transcript for concepts and themes. RESULTS: Interview
      narratives highlight the presence of the past alongside desires for protection
      from uncertain futures. We turn to Quesada and colleagues' concept structural
      vulnerability to outline the constraints posed by these women's positionalities
      as genocide survivors when faced with making decisions in an area with which they
      have little direct knowledge or background: cervical cancer prevention.
      CONCLUSION: Our study sheds light on the prioritization of various protective
      health practices, including but not exclusive to HPV vaccination, for Khmer
      mothers, as well as the rationalities informing decision-making regarding their
      daughters' health.

PMID- 24905059
TI  - Nonparametric Variable Selection for Predictive Models and Subpopulations in
      Clinical Trials.
AB  - Most clinical trials have heterogeneous treatment effect among patient
      individuals. It is desirable to identify a patient subpopulation, which has a
      stronger treatment effect than the rest of patients, so that researchers will be
      able to determine who will benefit the most or the least from the treatment and
      design treatment strategies accordingly. This paper develops a nonparametric
      method for predicting clinical response and identifying subpopulations. The
      method first selects predictors using kernel-based local regression and a forward
      procedure via F-tests. It then defines subpopulations with enhanced treatment
      effects based on the selected predictors and the nonparametric model of the
      clinical response. Simulation examples and a pharmacogenomics study of bortezomib
      in multiple myeloma demonstrate the proposed method and show favorable
      performances compared to other existing methods. The proposed method provides an
      alternative way to define subpopulations and is not limited by parametric models
      and their possible misspecification for the clinical response. 

PMID- 24905058
TI  - Liraglutide in the treatment of obesity.
AB  - INTRODUCTION: Obesity is a global epidemic with important healthcare and
      financial implications. Most current antiobesity pharmacological therapies are
      unsatisfactory due to undesirable side effects. Many drugs have been withdrawn
      due to safety concerns. Maintaining weight loss remains the Achilles' heel of
      antiobesity therapy. AREAS COVERED: This is an overview of the use of liraglutide
      for obesity treatment. Clinical efficacy on weight, cardiovascular parameters, as
      well as safety and tolerability issues are discussed. EXPERT OPINION: Liraglutide
      is a glucagon-like peptide 1 (GLP-1) receptor agonist, which has a protracted
      pharmacokinetic profile compared to native GLP-1 while maintaining its biological
      activity. It induces weight loss by reducing appetite and energy intake. It
      stimulates insulin release and decreases glucagon secretion in response to
      hyperglycaemia. Treatment with liraglutide, in addition with diet and exercise,
      induces sustained mean weight loss of 7.6 kg at 2 years (weight loss induced by
      orlistat = 5.7 kg, phentermine/topiramate controlled release 15/92 = 10.9 kg). It
      reduces blood pressure and improves glycaemic control, which has clinically
      relevant significance on reducing obesity-related morbidity and mortality.
      Liraglutide is reasonably well tolerated with gastrointestinal side effects being
      most commonly encountered. Novo Nordisk filed for regulatory approval of
      liraglutide 3.0 mg for obesity treatment in December 2013.

PMID- 24905060
TI  - Enterovirus 71 inhibits cellular type I interferon signaling by downregulating
      JAK1 protein expression.
AB  - Enterovirus 71 (EV71) infection can cause severe disease and lead to death in
      children. Recurring outbreaks of EV71 have been reported in several countries.
      Interferons (IFNs) have been used for decades to treat several types of viral
      infection, but have a limited ability to inhibit EV71 replication. Herein, we
      intend to investigate the mechanisms by which EV71 inhibits the cellular type I
      IFN response. In this study, MRC-5 (human embryonic lung fibroblast) or RD (human
      rhabdomyosarcoma) cells were infected with EV71, and then treated with or without
      IFN-alpha2b. Cells were harvested and analyzed by flow cytometry to determine the
      level of IFNAR1. Cell lysis were prepared to detect the levels of STAT1, STAT2,
      phosphorylated STAT1, phosphorylated STAT2, IFNAR1, JAK1, and TYK2 by Western
      blotting. The phosphorylation of STAT1 and STAT2 induced by IFN were inhibited
      without significant downregulation of IFNAR1 in EV71-infected cells. The EV71
      induced suppression of STAT1 and STAT2 phosphorylation was not rescued by the
      protein tyrosine phosphatases inhibitor, and was independent of suppressor of
      cytokine signaling protein 1/3 levels. The phosphorylation of JAK1 and TYK2 were
      inhibited accompanied by EV71-induced downregulation of JAK1, which occurred at a
      post-transcriptional level and was proteasome independent. JAK1 expression did
      not decrease, and IFN-alpha-stimulated STAT1 and STAT2 phosphorylation were not
      blocked in HEK293T cells overexpressing the EV71 viral protein 2A or 3C. This
      study demonstrates that EV71 inhibits the cellular type I IFN antiviral pathway
      by downregulating JAK1, while the expression of IFNAR1 does not significantly
      alter in EV71-infected cells. Additionally, the EV71 viral proteins 2A and 3C do
      not act as antagonists of cellular type I IFN signaling.

PMID- 24905061
TI  - Effects of rosiglitazone vs metformin on circulating osteoclast and osteogenic
      precursor cells in postmenopausal women with type 2 diabetes mellitus.
AB  - CONTEXT: Thiazolidinediones are associated with increased fractures in type 2
      diabetes mellitus (T2D). One explanation is that activation of peroxisome
      proliferator-activated receptor-gamma expression alters bone remodeling cells.
      OBJECTIVE: To investigate whether osteoclast and osteogenic precursor cells are
      altered by rosiglitazone (RSG) treatment in T2D as compared to metformin (MET)
      treatment. DESIGN: A randomized controlled trial of RSG or MET for 52 weeks,
      followed by 24 weeks of MET. SETTING: Data were generated at a tertiary care
      center. PATIENTS: Seventy-three T2D postmenopausal women participated. MAIN
      OUTCOME MEASURES: Peripheral blood mononuclear cells were isolated and cultured
      with receptor activator of nuclear factor kappaB ligand and stained for tartrate
      resistant acid phosphatase to measure circulating osteoclast precursors.
      Peripheral blood mononuclear cells were also characterized for osteogenic,
      endothelial, and calcification markers by flow cytometry with the ligands
      osteocalcin (OCN), CD34, and CD 146. RESULTS: Tartrate-resistant acid phosphatase
      positive cells increased between weeks 0 and 52 (RSG, 2.9 +/- 2 to 14.0 +/- 3
      U/L, P = .001; MET, 3.3 +/- 2 to 16.7 +/- 2 U/L, P = .001), increasing further in
      the RSG group after changing to MET (to 26.5 +/- 5 U/L, P = .05 vs wk 52). With
      RSG, OCN+ cells with CD34 but without CD146 fell from weeks 0 to 52 (20.1 +/- 1%
      to 15.5 +/- 2%; P = .03), remaining stable through week 76. The OCN+ cells
      lacking both CD34 and CD146 increased from weeks 0 to 52 (67.3 +/- 2 to 74.4 +/-
      2%; P = .02), but returned to baseline after switching to MET. CONCLUSION: In
      postmenopausal women with T2D, circulating osteoclast precursor cells increase
      with both RSG and MET, and increase further when switching from RSG to MET.
      Subpopulations of cells that may be involved in the osteogenic lineage pathway
      are also altered with RSG. Further work is necessary to elucidate how these
      changes may relate to fracture risk.

PMID- 24905062
TI  - A new type of natural bispecific antibody with potential protective effect in
      Hashimoto thyroiditis.
AB  - CONTEXT: As a new antibody concept, natural bispecific antibodies (nBsAbs) have
      been detected in long-term passive immunization and some diseases, but their
      potential immunomodulatory role remains unclear. Hashimoto thyroiditis (HT)
      appears to fulfill the condition for nBsAb production but has not yet been
      characterized. OBJECTIVE: The objective of the study was to identify a new nBsAb
      against thyroid peroxidase (TPO) and thyroglobulin (Tg) in HT patients and to
      preliminarily explore its immunomodulatory role. DESIGN, SETTING, AND PATIENTS:
      Serum samples were obtained from 136 HT patients, 92 diseased controls, and 99
      healthy controls for anti-TPO/Tg nBsAb detection. The relationship between anti
      TPO/Tg nBsAb and other clinical parameters was also analyzed. MAIN OUTCOME
      MEASURES: The anti-TPO/Tg nBsAb was detected using a double-antigen sandwich
      ELISA. Higher nBsAb levels were found to be associated with decreased
      inflammation in HT patients. RESULTS: The prevalence of anti-TPO/Tg nBsAb in HT
      was 44.9% (61 of 136), significantly higher than that of diseased controls (2.2%,
      2 of 92) (P < .0001) and healthy controls (0%, 0 of 99) (P < .0001). HT patients
      who were nBsAb positive were prone to have significantly lower levels of serum C
      reactive protein and TNF-alpha compared with the nBsAb-negative individuals (P <
      .05). The serum amyloid A and interferon-gamma levels also showed a similar trend
      in the two groups. The IgG subclass of anti-TPO/Tg nBsAb was IgG4. Further
      analysis showed a negative correlation between anti-TPO/Tg nBsAb and serum total
      IgG4 (r = -0.697, P = .025) in IgG4 thyroiditis patients. CONCLUSIONS: A new type
      of nBsAb against TPO and Tg in HT patients is identified. Our data also indicate
      a protective effect of anti-TPO/Tg nBsAb in the pathogenesis of HT and extend
      prior knowledge about nBsAb in diseases.

PMID- 24905063
TI  - Bone mineral density in young women with primary ovarian insufficiency: results
      of a three-year randomized controlled trial of physiological transdermal
      estradiol and testosterone replacement.
AB  - CONTEXT: Women with primary ovarian insufficiency have significantly lower serum
      estradiol and T levels compared with regularly menstruating women. They also have
      significantly reduced bone mineral density (BMD). OBJECTIVE: The objective of the
      study was to evaluate the efficacy of hormone replacement in maintaining BMD in
      these young women. DESIGN AND SETTING: This was a randomized, double-blind,
      single-center, placebo-controlled clinical trial at the National Institutes of
      Health clinical center (Bethesda, Maryland). PARTICIPANTS: Young women with
      primary ovarian insufficiency participated in the study. INTERVENTIONS: We
      compared the effect of estradiol and progestin replacement (n = 72) vs estradiol,
      progestin, and T replacement (n = 73) on BMD. We also compared findings with a
      contemporaneous control group of normal women (n = 70). All patients received
      transdermal estradiol (100 MUg/d) plus oral medroxyprogesterone acetate 10 mg/d
      (12 d/mo) for a 3-month run-in period before being randomized in a double-blinded
      fashion to the addition of transdermal T (150 MUg/d) or placebo. MAIN OUTCOME
      MEASURE: Change in BMD at the femoral neck was measured by dual-energy x-ray
      absorptiometry. RESULTS: At screening, patients had significantly lower femoral
      neck BMD compared with control women (0.77 vs 0.81 g/cm(2), P = .001) and did not
      differ in body mass index, age at menarche, or education level. Normal control
      women lost femoral neck BMD over the study period, whereas patients on estradiol
      and progestin therapy gained BMD; and at the end of the study period, femoral
      neck BMD of patients on estradiol and progestin therapy did not differ from that
      of control women (0.80 g/cm(2) in both groups, P = .9). The addition of T showed
      no further benefit (percentage change in BMD 3.9 vs 2.4, respectively, P = .9).
      Nonetheless, using a repeated-measures model, the T group achieved a mean BMD in
      the femoral neck 0.015 g/cm(2) higher than the placebo group at 3 years (95%
      confidence interval -0.005 to 0.034, P = .13). Similar findings were observed in
      the lumbar spine BMD as well. CONCLUSION: Long-term physiological transdermal
      estradiol replacement in combination with oral medroxyprogesterone acetate
      restores mean femoral neck BMD to normal in young women with spontaneous 46,XX
      primary ovarian insufficiency. However, the addition of physiological transdermal
      T replacement did not provide additional benefit.

PMID- 24905064
TI  - ARMC5 mutations are common in familial bilateral macronodular adrenal
      hyperplasia.
AB  - CONTEXT: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of
      adrenal Cushing's syndrome. Familial cases have been reported, but at the time we
      conducted this study, the genetic basis of BMAH was unknown. Recently, germline
      variants of armadillo repeat containing 5 (ARMC5) in patients with isolated BMAH
      and somatic, second-hit mutations in tumor nodules, were identified. OBJECTIVE:
      Our objective was to identify the genetic basis of familial BMAH. DESIGN: We
      performed whole exome capture and sequencing of 2 affected individuals from each
      of 4 BMAH families (BMAH-01, BMAH-02, BMAH-03, and BMAH-05). Based on clinical
      evaluation, there were 7, 3, 3, and 4 affected individuals in these families,
      respectively. Sanger sequencing of ARMC5 was performed in 1 other BMAH kindred,
      BMAH-06. RESULTS: Exome sequencing identified novel variants Chr16:g.31477540,
      c.2139delT, p.(Thr715Leufs*1) (BMAH-02) and Chr16:g.31473811, c.943C->T,
      p.(Arg315Trp) (BMAH-03) in ARMC5 (GRch37/hg19), validated by Sanger sequencing.
      BMAH-01 had a recently reported mutation Chr16:g.31476121, c.1777C->T,
      p.(Arg593Trp). Sanger sequencing of ARMC5 in BMAH-06 identified a previously
      reported mutation, Chr16:g. 31473688; c.799C->T, p.(Arg267*). The genetic basis
      of BMAH in BMAH-05 was not identified. CONCLUSIONS: Our studies have detected
      ARMC5 mutations in 4 of 5 BMAH families tested, confirming that these mutations
      are a frequent cause of BMAH. Two of the 4 families had novel mutations,
      indicating allelic heterogeneity. Preclinical evaluation did not predict mutation
      status. The ARMC5-negative family had unusual prominent hyperaldosteronism.
      Further studies are needed to determine the penetrance of BMAH in ARMC5 mutation
      positive relatives of affected patients, the practical utility of genetic
      screening and genotype-phenotype correlations.

PMID- 24905065
TI  - Parathyroid hormone-related peptide (PTHrP) secretion by gastroenteropancreatic
      neuroendocrine tumors (GEP-NETs): clinical features, diagnosis, management, and
      follow-up.
AB  - CONTEXT: Only a small number of case reports has been published on patients with
      PTHrP-hypersecreting metastatic gastroenteropancreatic (GEP) neuroendocrine
      tumors (NETs). OBJECTIVE: The objective of this study was to evaluate the
      clinical, biochemical, and radiological features, management, and treatment
      outcome of patients with PTHrP-hypersecreting GEP-NETs. DESIGN: Retrospective
      case series. SETTING: Tertiary referral hospital. MAIN OUTCOME MEASURES:
      Clinical, biochemical, and radiological features were measured, as well as
      response to therapy and survival. PATIENTS: Ten patients with PTHrP-secreting GEP
      NETs (nine pancreatic and one unknown primary) with a median age of 50.4 years
      (range, 38.3-61.1) were studied. Multiple endocrine neoplasia type 1 patients
      were excluded. RESULTS: The median follow-up was 57.2 months (range, 11.6-204.5
      mo). Median overall survival was 86.0 months. In total, 51 different treatment
      interventions and combinations were applied. In seven of the 10 patients,
      somatostatin analog (SSA) treatment resulted in a temporary normalization of
      serum calcium levels with a long-term response observed in two patients (up to
      35.2 mo). Peptide receptor radiotherapy (PRRT) with radiolabeled SSAs induced
      long-term responses ranging from 9.0-49.0 months in four of six patients treated
      with PRRT. CONCLUSIONS: Hypersecretion of PTHrP by metastatic GEP-NETs is very
      rare and seems to be exclusively associated with metastatic pancreatic NETs.
      PTHrP production has major clinical impact because poorly controllable
      hypercalcemia is associated with increased morbidity and mortality. The most
      successful treatment options for PTHrP-producing GEP-NETs are SSAs and PRRT using
      radiolabeled SSAs. Isotonic saline and bisphosphonates can be considered as
      supportive therapies.

PMID- 24905066
TI  - Genetic predictors of long-term response to growth hormone (GH) therapy in
      children with GH deficiency and Turner syndrome: the influence of a SOCS2
      polymorphism.
AB  - BACKGROUND: There is great interindividual variability in the response to GH
      therapy. Ascertaining genetic factors can improve the accuracy of growth response
      predictions. Suppressor of cytokine signaling (SOCS)-2 is an intracellular
      negative regulator of GH receptor (GHR) signaling. OBJECTIVE: The objective of
      the study was to assess the influence of a SOCS2 polymorphism (rs3782415) and its
      interactive effect with GHR exon 3 and -202 A/C IGFBP3 (rs2854744) polymorphisms
      on adult height of patients treated with recombinant human GH (rhGH). DESIGN AND
      PATIENTS: Genotypes were correlated with adult height data of 65 Turner syndrome
      (TS) and 47 GH deficiency (GHD) patients treated with rhGH, by multiple linear
      regressions. Generalized multifactor dimensionality reduction was used to
      evaluate gene-gene interactions. RESULTS: Baseline clinical data were
      indistinguishable among patients with different genotypes. Adult height SD scores
      of patients with at least one SOCS2 single-nucleotide polymorphism rs3782415-C
      were 0.7 higher than those homozygous for the T allele (P < .001). SOCS2 (P =
      .003), GHR-exon 3 (P= .016) and -202 A/C IGFBP3 (P = .013) polymorphisms,
      together with clinical factors accounted for 58% of the variability in adult
      height and 82% of the total height SD score gain. Patients harboring any two
      negative genotypes in these three different loci (homozygosity for SOCS2 T
      allele; the GHR exon 3 full-length allele and/or the -202C-IGFBP3 allele) were
      more likely to achieve an adult height at the lower quartile (odds ratio of 13.3;
      95% confidence interval of 3.2-54.2, P = .0001). CONCLUSION: The SOCS2
      polymorphism (rs3782415) has an influence on the adult height of children with TS
      and GHD after long-term rhGH therapy. Polymorphisms located in GHR, IGFBP3, and
      SOCS2 loci have an influence on the growth outcomes of TS and GHD patients
      treated with rhGH. The use of these genetic markers could identify among rhGH
      treated patients those who are genetically predisposed to have less favorable
      outcomes.

PMID- 24905067
TI  - Multiple metabolic genetic risk scores and type 2 diabetes risk in three
      racial/ethnic groups.
AB  - CONTEXT/RATIONALE: Meta-analyses of genome-wide association studies have
      identified many single-nucleotide polymorphisms associated with various metabolic
      and cardiovascular traits, offering us the opportunity to learn about and
      capitalize on the links between cardiometabolic traits and type 2 diabetes (T2D).
      DESIGN: In multiple datasets comprising over 30 000 individuals and 3
      ethnic/racial groups, we calculated 17 genetic risk scores (GRSs) for glycemic,
      anthropometric, lipid, hemodynamic, and other traits, based on the results of
      recent trait-specific meta-analyses of genome-wide association studies, and
      examined associations with T2D risk. Using a training-testing procedure, we
      evaluated whether additional GRSs could contribute to risk prediction. RESULTS:
      In European Americans, we find that GRSs for T2D, fasting glucose, fasting
      insulin, and body mass index are associated with T2D risk. In African Americans,
      GRSs for T2D, fasting insulin, and waist-to-hip ratio are associated with T2D. In
      Hispanic Americans, GRSs for T2D and body mass index are associated with T2D. We
      observed a trend among European Americans suggesting that genetic risk for
      hyperlipidemia is inversely associated with T2D risk. The use of additional GRSs
      resulted in only small changes in prediction accuracy in multiple independent
      validation datasets. CONCLUSIONS: The analysis of multiple GRSs can shed light on
      T2D etiology and how it varies across ethnic/racial groups. Our findings using
      multiple GRSs are consistent with what is known about the differences in T2D
      pathogenesis across racial/ethnic groups. However, further work is needed to
      understand the putative inverse correlation of genetic risk for hyperlipidemia
      and T2D risk and to develop ethnic-specific GRSs.

PMID- 24905068
TI  - The acute effects of interval- Vs continuous-walking exercise on glycemic control
      in subjects with type 2 diabetes: a crossover, controlled study.
AB  - CONTEXT: Glycemic control improves with physical activity, but the optimal
      exercise mode is unknown. OBJECTIVE: The objective of the study was to determine
      whether interval-based exercise improves postprandial glucose tolerance and free
      living glycemia more than oxygen consumption- and time duration-matched
      continuous exercise. DESIGN: This was a crossover, controlled study with trials
      performed in randomized order. SETTING: The study was conducted in hospitalized
      and ambulatory care. PATIENTS: PATIENTS diagnosed with type 2 diabetes mellitus
      (n=10, no withdrawals) participated in the study. INTERVENTIONS: Subjects
      performed three 1-hour interventions: 1) interval walking (IW; repeated cycles of
      3 min of slow and fast walking); 2) continuous walking (CW); and 3) control
      (CON). Oxygen consumption (VO2) was measured continuously to match mean VO2
      between exercise sessions (~75% VO2peak). MAIN OUTCOME MEASURES: A mixed-meal
      tolerance test (MMTT; 450 kcal, 55% carbohydrate) with stable glucose isotopic
      tracers was provided after each intervention, and glucose kinetics were measured
      during the following 4 hours. Free-living glycemic control was assessed for
      approximately 32 hours after the MMTT using continuous glucose monitoring.
      RESULTS: VO2 was well matched between the exercise interventions. IW decreased
      the mean and maximal incremental plasma glucose during the MMTT when compared
      with the CON (mean 1.2 +/- 0.4 vs 2.0 +/- 0.5 mmol/L, P < .001; maximal 3.7 +/-
      0.6 vs 4.6 +/- 0.7 mmol/L, P = .005) and mean when compared with CW (1.7 +/- 0.4
      mmol/L, P = .02). No differences in the mean or maximal incremental plasma
      glucose values were seen between the CW and CON. The metabolic clearance rate of
      glucose during the MMTT was increased in the IW compared with CW (P = .049) and
      CON (P < .001). Continuous glucose monitoring mean glucose was reduced in IW
      compared with CW for the rest of the intervention day (8.2 +/- 0.4 vs 9.3 +/- 0.7
      mmol/L, P = .03), whereas no differences were found between IW and CW the
      following day. CONCLUSIONS: One interval-based exercise session improves glycemic
      control in type 2 diabetes mellitus subjects when compared with an oxygen
      consumption- and time duration-matched continuous exercise session.

PMID- 24905069
TI  - Including illness behavior in the assessment of endocrine patients.

PMID- 24905070
TI  - The behavioral intervention technology model: an integrated conceptual and
      technological framework for eHealth and mHealth interventions.
AB  - A growing number of investigators have commented on the lack of models to inform
      the design of behavioral intervention technologies (BITs). BITs, which include a
      subset of mHealth and eHealth interventions, employ a broad range of
      technologies, such as mobile phones, the Web, and sensors, to support users in
      changing behaviors and cognitions related to health, mental health, and wellness.
      We propose a model that conceptually defines BITs, from the clinical aim to the
      technological delivery framework. The BIT model defines both the conceptual and
      technological architecture of a BIT. Conceptually, a BIT model should answer the
      questions why, what, how (conceptual and technical), and when. While BITs
      generally have a larger treatment goal, such goals generally consist of smaller
      intervention aims (the "why") such as promotion or reduction of specific
      behaviors, and behavior change strategies (the conceptual "how"), such as
      education, goal setting, and monitoring. Behavior change strategies are
      instantiated with specific intervention components or "elements" (the "what").
      The characteristics of intervention elements may be further defined or modified
      (the technical "how") to meet the needs, capabilities, and preferences of a user.
      Finally, many BITs require specification of a workflow that defines when an
      intervention component will be delivered. The BIT model includes a technological
      framework (BIT-Tech) that can integrate and implement the intervention elements,
      characteristics, and workflow to deliver the entire BIT to users over time. This
      implementation may be either predefined or include adaptive systems that can
      tailor the intervention based on data from the user and the user's environment.
      The BIT model provides a step towards formalizing the translation of developer
      aims into intervention components, larger treatments, and methods of delivery in
      a manner that supports research and communication between investigators on how to
      design, develop, and deploy BITs. 

PMID- 24905071
TI  - Spontaneous germline excision of Tol1, a DNA-based transposable element naturally
      occurring in the medaka fish genome.
AB  - DNA-based transposable elements are ubiquitous constituents of eukaryotic
      genomes. Vertebrates are, however, exceptional in that most of their DNA-based
      elements appear to be inactivated. The Tol1 element of the medaka fish, Oryzias
      latipes, is one of the few elements for which copies containing an undamaged gene
      have been found. Spontaneous transposition of this element in somatic cells has
      previously been demonstrated, but there is only indirect evidence for its
      germline transposition. Here, we show direct evidence of spontaneous excision in
      the germline. Tyrosinase is the key enzyme in melanin biosynthesis. In an albino
      laboratory strain of medaka fish, which is homozygous for a mutant tyrosinase
      gene in which a Tol1 copy is inserted, we identified de novo reversion mutations
      related to melanin pigmentation. The gamete-based reversion rate was as high as
      0.4%. The revertant fish carried the tyrosinase gene from which the Tol1 copy had
      been excised. We previously reported the germline transposition of Tol2, another
      DNA-based element that is thought to be a recent invader of the medaka fish
      genome. Tol1 is an ancient resident of the genome. Our results indicate that even
      an old element can contribute to genetic variation in the host genome as a
      natural mutator. 

PMID- 24905072
TI  - A tool for classifying individuals with chronic back pain: using multivariate
      pattern analysis with functional magnetic resonance imaging data.
AB  - Chronic pain is one of the most prevalent health problems in the world today, yet
      neurological markers, critical to diagnosis of chronic pain, are still largely
      unknown. The ability to objectively identify individuals with chronic pain using
      functional magnetic resonance imaging (fMRI) data is important for the
      advancement of diagnosis, treatment, and theoretical knowledge of brain processes
      associated with chronic pain. The purpose of our research is to investigate
      specific neurological markers that could be used to diagnose individuals
      experiencing chronic pain by using multivariate pattern analysis with fMRI data.
      We hypothesize that individuals with chronic pain have different patterns of
      brain activity in response to induced pain. This pattern can be used to classify
      the presence or absence of chronic pain. The fMRI experiment consisted of
      alternating 14 seconds of painful electric stimulation (applied to the lower
      back) with 14 seconds of rest. We analyzed contrast fMRI images in stimulation
      versus rest in pain-related brain regions to distinguish between the groups of
      participants: 1) chronic pain and 2) normal controls. We employed supervised
      machine learning techniques, specifically sparse logistic regression, to train a
      classifier based on these contrast images using a leave-one-out cross-validation
      procedure. We correctly classified 92.3% of the chronic pain group (N = 13) and
      92.3% of the normal control group (N = 13) by recognizing multivariate patterns
      of activity in the somatosensory and inferior parietal cortex. This technique
      demonstrates that differences in the pattern of brain activity to induced pain
      can be used as a neurological marker to distinguish between individuals with and
      without chronic pain. Medical, legal and business professionals have recognized
      the importance of this research topic and of developing objective measures of
      chronic pain. This method of data analysis was very successful in correctly
      classifying each of the two groups. 

PMID- 24905073
TI  - Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice
      by elevating body defense capacity.
AB  - Quercetin is a plant-derived flavonoid that is widely distributed in nature. The
      present study is designed to analyze the underlying mechanism in the protection
      of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury
      in vivo. Serum transaminases, total bilirubin analysis, and liver histological
      evaluation demonstrated the protection of quercetin against clivorine-induced
      liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin
      reduced the increased amount of liver apoptotic cells induced by clivorine.
      Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved
      activation of caspase-3 induced by clivorine. Results also showed that quercetin
      reduced the increase in liver glutathione and lipid peroxidative product
      malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver
      immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results
      of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array
      demonstrated that the expression of genes related with oxidative or metabolic
      stress and heat shock was obviously altered after quercetin treatment. Some of
      the alterations were confirmed by real-time PCR. Our results demonstrated that
      quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting
      apoptotic cell death and ameliorating oxidative stress injury. This protection
      may be caused by the elevation of the body defense capacity induced by quercetin.

PMID- 24905074
TI  - Cell-based biosensors and their application in biomedicine.

PMID- 24905076
TI  - Theoretical investigation of the open circuit voltage: P3HT/9,9'
      bisfluorenylidene derivative devices.
AB  - The calculation of the power conversion efficiency (PCE) value for a bulk
      heterojunction (BHJ) organic solar cell is complex due to the wide number of
      parameters involved in the processes. This study focuses the attention on the
      molecular parameters involved into the open circuit voltage and the PCE
      definitions and in particular on the electronic coupling and on the lowest
      unoccupied molecular orbital (LUMO) of the acceptor. A simplified model system
      composed by a polymer as donor and a novel class of molecules (9,9'
      bisfluorenylidene derivatives) as acceptor has been proposed as prototype to
      simulate the BHJ organic solar cell interface. Several substituents on different
      positions are tested and the chemical nature/position of substituents have a
      relevant influence on the electronic coupling and energy level values.
      Geometrical and electronic properties are obtained using density functional
      theory (DFT) and time-dependent (TD)-DFT calculations, respectively. A new
      hypothesis suggests that the minimization of the electronic coupling between the
      LUMO of the acceptor and the highest occupied molecular orbital (HOMO) of the
      donor can enhance the PCE reducing the recombination interface processes and
      calculations showing the possibility to minimize this parameter and fine-tune
      acceptor energy level through the acceptor functionalization. An accurate balance
      between electronic coupling and on the LUMO of the acceptor allows to propose the
      more performing candidate as electron acceptor in a P3HT/99'BF derivative BHJ
      solar cell. 

PMID- 24905075
TI  - Catalytic enantioselective iodoaminocyclization of hydrazones.
AB  - The first catalytic enantioselective iodoaminocyclization of beta,gamma
      unsaturated hydrazones has been developed with the help of a trans-1,2
      diaminocyclohexane-derived bifunctional thiourea catalyst and allows for the
      direct access to Delta(2)-pyrazolines containing a quaternary stereogenic center
      in high yield with good enantioselectivity (up to 95% yield and 95:5 er). 

PMID- 24905077
TI  - Molecular level description of the sorptive fractionation of a fulvic acid on
      aluminum oxide using electrospray ionization Fourier transform mass spectrometry.
AB  - We addressed here, by means of electrospray ionization mass spectrometry (ESI-MS)
      with ultrahigh resolution, the molecular level fractionation of a reference
      fulvic acid (SRFA) during its sorption at an alumina surface, taken as a model
      for surfaces of natural aluminum oxide hydrates. Examination of ESI-MS spectra of
      a native SRFA solution and of supernatants collected in sorption experiments at
      acidic pH showed that the ~5700 compounds identified in the native solution were
      partitioned between the solution and alumina surface to quite varying degrees.
      Compounds showing the highest affinity for the surface were aromatic compounds
      with multiple oxygenated functionalities, polycyclic aromatic compounds depleted
      of hydrogen and carrying few oxygenated groups, and aliphatic compounds with very
      high O/C values, highlighting the fact that SRFA constituents were sorbed mainly
      via chemical sorption involving their oxygenated functionalities. We observed an
      inverse correlation between the degree of sorption of a molecule within a CH2
      series and its number of CH2 groups and a positive correlation between the degree
      of sorption and the number of CO2 groups in a COO series, which was remarkable.
      These correlations provide evidence at the molecular scale that molecule acidity
      is the key parameter governing fulvic acid (FA) sorptive fractionation, and they
      are useful for predicting sorption of FA at a natural oxide surface. 

PMID- 24905079
TI  - Cu-catalyzed cascades to carbocycles: union of diaryliodonium salts with alkenes
      or alkynes exploiting remote carbocations.
AB  - Copper-catalyzed cascade reactions between alkenes or alkynes and diaryliodonium
      salts form carbocyclic products in a single step. Arylation of the unsaturated
      functional group is proposed to form a carbocation intermediate that facilitates
      hydride shift pathways to translocate the positive charge to a remote position
      and enables ring formation via a Friedel-Crafts-type reaction. 

PMID- 24905078
TI  - Bottom-up low molecular weight heparin analysis using liquid chromatography
      Fourier transform mass spectrometry for extensive characterization.
AB  - Low molecular weight heparins (LMWHs) are heterogeneous, polydisperse, and highly
      negatively charged mixtures of glycosaminoglycan chains prescribed as
      anticoagulants. The detailed characterization of LMWH is important for the drug
      quality assurance and for new drug research and development. In this study,
      online hydrophilic interaction chromatography (HILIC) Fourier transform mass
      spectrometry (FTMS) was applied to analyze the oligosaccharide fragments of LMWHs
      generated by heparin lyase II digestion. More than 40 oligosaccharide fragments
      of LMWH were quantified and used to compare LMWHs prepared by three different
      manufacturers. The quantified fragment structures included unsaturated
      disaccharides/oligosaccharides arising from the prominent repeating units of
      these LMWHs, 3-O-sulfo containing tetrasaccharides arising from their
      antithrombin III binding sites, 1,6-anhydro ring-containing oligosaccharides
      formed during their manufacture, saturated uronic acid oligosaccharides coming
      from some chain nonreducing ends, and oxidized linkage region oligosaccharides
      coming from some chain reducing ends. This bottom-up approach provides rich
      detailed structural analysis and quantitative information with high accuracy and
      reproducibility. When combined with the top-down approach, HILIC LC-FTMS based
      analysis should be suitable for the advanced quality control and quality
      assurance in LMWH production. 

PMID- 24905080
TI  - Matrix isolation, zero-field splitting parameters, and photoreactions of septet
      2,4,6-trinitrenopyrimidines.
AB  - The key intermediates of decomposition of high-energy 2,4,6-triazidopyrimidine
      and its 5-chloro-substituted derivative, the detonation of which is used for
      preparation of carbon nitrides, were investigated using electron paramagnetic
      resonance (EPR) spectroscopy in combination with quantum chemical calculations.
      The decomposition of the triazides was carried out photochemically, using the
      matrix isolation technique. The photodecomposition of both triazides with 254 nm
      light in argon matrices at 5 K occurred selectively to subsequently give the
      corresponding triplet 4,6-diazido-2-nitrenopyrimidines, quintet 4-azido-2,6
      dinitrenopyrimidines, and septet 2,4,6-trinitrenopyrimidines. The latter were
      photochemically unstable and decomposed to form triplet nitrenes NCN and NNC as
      well as triplet carbenes NCCCN, HCCN, and HCCCCN. The results obtained provide
      important information about exchange interactions in high-spin nitrenes with the
      pyrimidine ring and the mechanism of the formation of carbon nitrides during
      thermolysis of 2,4,6-triazidopyrimidine. 

PMID- 24905081
TI  - Parental involvement in homework: relations with parent and student achievement
      related motivational beliefs and achievement.
AB  - BACKGROUND: Parental involvement in homework is a home-based type of involvement
      in children's education. Research and theory suggest that it is beneficial for
      learning and achievement under certain conditions and for particular groups of
      individuals. AIMS: The study examined whether different types of parents'
      involvement in homework (autonomy support, control, interference, cognitive
      engagement) (1) are predicted by their mastery and performance goals for their
      child and their beliefs of the child's academic efficacy, and (2) predict student
      achievement goal orientations, efficacy beliefs, and achievement. Grade-level
      differences were also investigated. SAMPLE: The sample consisted of 282
      elementary school (5th grade) and junior high school students (8th grade) and one
      of their parents. METHODS: Surveys were used for data collection. Structural
      equation modelling was applied for data analysis. RESULTS: (1) Autonomy support
      during homework was predicted by parent mastery goal, parents' control and
      interference by their performance goal and perceptions of child efficacy, and
      cognitive engagement as supplementary to homework by parent perceptions of child
      efficacy. (2) Parental autonomy support, control, and interference were
      differentially associated with student mastery and performance goal orientations,
      whereas parent cognitive engagement was associated with student efficacy beliefs.
      (3) The structural model was the same for elementary and junior high school
      students but the latent means for a number of variables were different.
      CONCLUSION: Different types of parental involvement in homework were associated
      with different outcomes with parent autonomy support to be the most beneficial
      one.

PMID- 24905082
TI  - Neuron type- and input pathway-dependent expression of Slc4a10 in adult mouse
      brains.
AB  - Slc4a10 was originally identified as a Na(+) -driven Cl(-) /HCO3 (-) exchanger
      NCBE that transports extracellular Na(+) and HCO3 (-) in exchange for
      intracellular Cl(-) , whereas other studies argue against a Cl(-) -dependence for
      Na(+) -HCO3 (-) transport, and thus named it the electroneutral Na(+) /HCO3 (-)
      cotransporter NBCn2. Here we investigated Slc4a10 expression in adult mouse
      brains by in situ hybridization and immunohistochemistry. Slc4a10 mRNA was widely
      expressed, with higher levels in pyramidal cells in the hippocampus and cerebral
      cortex, parvalbumin-positive interneurons in the hippocampus, and Purkinje cells
      (PCs) in the cerebellum. Immunohistochemistry revealed an uneven distribution of
      Slc4a10 within the somatodendritic compartment of cerebellar neurons. In the
      cerebellar molecular layer, stellate cells and their innervation targets (i.e. PC
      dendrites in the superficial molecular layer) showed significantly higher
      labeling than basket cells and their targets (PC dendrites in the basal molecular
      layer and PC somata). Moreover, the distal dendritic trees of PCs (i.e. parallel
      fiber-targeted dendrites) had significantly greater labeling than the proximal
      dendrites (climbing fiber-targeted dendrites). These observations suggest that
      Slc4a10 expression is regulated in neuron type- and input pathway-dependent
      manners. Because such an elaborate regulation is also found for K(+) -Cl(-)
      cotransporter KCC2, a major neuronal Cl(-) extruder, we compared their
      expression. Slc4a10 and KCC2 overlapped in most somatodendritic elements.
      However, relative abundance was largely complementary in the cerebellar cortex,
      with particular enrichments of Slc4a10 in PC dendrites and KCC2 in molecular
      layer interneurons, granule cells and PC somata. These properties might reflect
      functional redundancy and distinction of these transporters, and their
      differential requirements by individual neurons and respective input domains. 

PMID- 24905083
TI  - Data Pre-Processing for Label-Free Multiple Reaction Monitoring (MRM)
      Experiments.
AB  - Multiple Reaction Monitoring (MRM) conducted on a triple quadrupole mass
      spectrometer allows researchers to quantify the expression levels of a set of
      target proteins. Each protein is often characterized by several unique peptides
      that can be detected by monitoring predetermined fragment ions, called
      transitions, for each peptide. Concatenating large numbers of MRM transitions
      into a single assay enables simultaneous quantification of hundreds of peptides
      and proteins. In recognition of the important role that MRM can play in
      hypothesis-driven research and its increasing impact on clinical proteomics,
      targeted proteomics such as MRM was recently selected as the Nature Method of the
      Year. However, there are many challenges in MRM applications, especially data pre
      processing where many steps still rely on manual inspection of each observation
      in practice. In this paper, we discuss an analysis pipeline to automate MRM data
      pre-processing. This pipeline includes data quality assessment across replicated
      samples, outlier detection, identification of inaccurate transitions, and data
      normalization. We demonstrate the utility of our pipeline through its
      applications to several real MRM data sets. 

PMID- 24905084
TI  - Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive
      urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a
      retrospective international study of >1500 patients.
AB  - OBJECTIVE: To compare outcomes of patients with lymph node (LN)-positive
      urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based
      combined adjuvant chemotherapy (AC) after radical cystectomy (RC). PATIENTS AND
      METHODS: We retrospectively analysed 1523 patients with LN-positive UCB, who
      underwent RC with bilateral pelvic LN dissection. All patients had no evidence of
      disease after RC. AC was administered within 3 months. Competing-risks models
      were applied to compare UCB-related mortality. RESULTS: Of the 1523 patients, 874
      (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates
      for all patients were 16%, 36% and 56%, respectively. Administration of AC was
      associated with an 18% relative reduction in the risk of UCB-related death
      (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5%
      at 5 years. The positive effect of AC was detectable in patients aged <=70 years,
      in women, in pT3-4 disease, and in those with a higher LN density and
      lymphovascular invasion. This study is limited by its retrospective and non
      randomised design, selection bias, the absence of central pathological review and
      lack in standardisation of LN dissection and cisplatin-based protocols.
      CONCLUSION: AC seems to reduce UCB-related mortality in patients with LN-positive
      UCB after RC. Younger patients, women and those with high-risk features such as
      pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit
      most. Appropriately powered prospective randomised trials are necessary to
      confirm these findings.

PMID- 24905085
TI  - Renin-angiotensin system and fibrosis in non-alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Therapeutic options are limited for patients with non
      alcoholic fatty liver disease (NAFLD). One promising approach is the attenuation
      of necroinflammation and fibrosis by inhibition of the renin-angiotensin system
      (RAS). We explored whether the risk of fibrosis was associated with the use of
      commonly used medications in NAFLD patients with hypertension. Specifically, we
      sought to determine the association between RAS blocking agents and severity of
      hepatic fibrosis in NAFLD patients with hypertension. METHODS: Cross-sectional
      study where clinical information including demographics, anthropometry, medical
      history, concomitant medication use, biochemical and histological features were
      ascertained in 290 hypertensive patients with biopsy proven NAFLD followed at two
      hepatology outpatient clinics. Stage of hepatic fibrosis was compared in patients
      with and without RAS blocker use. Other risk factors for fibrosis were evaluated
      from the electronic medical records and patient follow-up. RESULTS: Baseline
      characteristics of hypertensive patients treated with and without RAS blockers
      were similar except for less ballooning (1.02 vs. 1.31, P = 0.001) and lower
      fibrosis stage (1.63 vs. 2.16, P = 0.002) in patients on RAS blockers On
      multivariate analysis, advancing age (OR: 1.04; 95%CI: 1.01-1.06, P = 0.012) and
      presence of diabetes (OR: 2.55; 95%CI: 1.28-5.09, P = 0.008) had an independent
      positive association, while use of RAS blockers (OR: 0.37; 95%CI: 0.21-0.65, P =
      0.001) and statins (OR: 0.52; 95%CI: 0.29-0.93, P = 0.029) had a negative
      association with advanced fibrosis. CONCLUSION: Hypertensive patients with NAFLD
      on baseline RAS blockers had less advanced hepatic fibrosis suggesting a
      beneficial effect of RAS blockers in NAFLD.

PMID- 24905087
TI  - Microanalysis of thermal-induced changes at the resin-dentin interface.
AB  - The purpose of this study was to evaluate the ability of two dentin adhesive
      systems to induce remineralization in the bonded dentin interface after in vitro
      thermo-cycling. Dentin surfaces were treated with two different adhesive
      approaches: (1) 37% phosphoric acid (PA) plus an "etch-and-rinse" dentin adhesive
      (single bond, SB) (PA+SB) or (2) application of a "self-etch" dentin adhesive
      (Clearfil SE bond, SEB). Three groups were established: (i) 24 h or (ii) 3 m
      storage, and (iii) specimens submitted to thermal cycling (100,000 cy/5 and
      55oC). Atomic force microscopy imaging/nanoindentation, Raman
      spectroscopy/cluster analysis with dye-assisted confocal laser scanning
      microscopy (CLSM) evaluation and Masson's trichrome staining assessments were
      implemented for characterization. Thermo-cycling increased nanohardness in PA+SB
      at the hybrid layer (HL) and in SEB at the bottom of the HL (BHL). Young's
      modulus increased at both the HL and BHL in SEB and at the HL in PA+SB, after
      thermal stress. Cluster analysis demonstrated an augmentation of the mineral
      matrix ratio in thermo-cycled specimens. CLSM showed a decrease of both
      micropermeability and nanoleakage after thermo-cycling in PA+SB, and were
      completely absent in SEB. Trichrome staining reflected a scarce demineralized
      front in PA+SB after thermo-cycling and total remineralization in SEB. 

PMID- 24905086
TI  - Microbial lipids reveal carbon assimilation patterns on hydrothermal sulfide
      chimneys.
AB  - Sulfide 'chimneys' characteristic of seafloor hydrothermal venting are diverse
      microbial habitats. 13C/12C ratios of microbial lipids have rarely been used to
      assess carbon assimilation pathways on these structures, despite complementing
      gene- and culture-based approaches. Here, we integrate analyses of the diversity
      of intact polar lipids (IPL) and their side-chain delta13C values (delta13
      C(lipid)) with 16S rRNA gene-based phylogeny to examine microbial carbon flow on
      active and inactive sulfide structures from the Manus Basin. Surficial crusts of
      active structures, dominated by Epsilonproteobacteria, yield bacterial
      delta13C(lipid) values higher than biomass delta13C (total organic carbon),
      implicating autotrophy via the reverse tricarboxylic acid cycle. Our data also
      suggest delta13C(lipid) values vary on individual active structures without
      accompanying microbial diversity changes. Temperature and/or dissolved substrate
      effects - likely relating to variable advective-diffusive fluxes to chimney
      exteriors - may be responsible for differing 13C fractionation during
      assimilation. In an inactive structure, delta13C(lipid) values lower than biomass
      delta13C and a distinctive IPL and 16S rRNA gene diversity suggest a shift to a
      more diverse community and an alternate carbon assimilation pathway after venting
      ceases. We discuss here the potential of IPL and delta13C(lipid) analyses to
      elucidate carbon flow in hydrothermal structures when combined with other
      molecular tools.

PMID- 24905088
TI  - DNA mediated wire-like clusters of self-assembled TiO2 nanomaterials:
      supercapacitor and dye sensitized solar cell applications.
AB  - A new route for the formation of wire-like clusters of TiO2 nanomaterials self
      assembled in DNA scaffold within an hour of reaction time is reported. TiO2
      nanomaterials are synthesized by the reaction of titanium-isopropoxide with
      ethanol and water in the presence of DNA under continuous stirring and heating at
      60  degrees C. The individual size of the TiO2 NPs self-assembled in DNA and the
      diameter of the wires can be tuned by controlling the DNA to Ti-salt molar ratios
      and other reaction parameters. The eventual diameter of the individual particles
      varies between 15 +/- 5 nm ranges, whereas the length of the nanowires varies in
      the 2-3 MUm range. The synthesized wire-like DNA-TiO2 nanomaterials are excellent
      materials for electrochemical supercapacitor and DSSC applications. From the
      electrochemical supercapacitor experiment, it was found that the TiO2
      nanomaterials showed different specific capacitance (Cs) values for the various
      nanowires, and the order of Cs values are as follows: wire-like clusters (small
      size) > wire-like clusters (large size). The highest Cs of 2.69 F g(-1) was
      observed for TiO2 having wire-like structure with small sizes. The study of the
      long term cycling stability of wire-like clusters (small size) electrode were
      shown to be stable, retaining ca. 80% of the initial specific capacitance, even
      after 5000 cycles. The potentiality of the DNA-TiO2 nanomaterials was also tested
      in photo-voltaic applications and the observed efficiency was found higher in the
      case of wire-like TiO2 nanostructures with larger sizes compared to smaller
      sizes. In future, the described method can be extended for the synthesis of other
      oxide based materials on DNA scaffold and can be further used in other
      applications like sensors, Li-ion battery materials or treatment for
      environmental waste water.

PMID- 24905090
TI  - Calcium sensing receptor modulates extracellular calcium entry and proliferation
      via TRPC3/6 channels in cultured human mesangial cells.
AB  - Calcium-sensing receptor (CaSR) has been demonstrated to be present in several
      tissues and cells unrelated to systemic calcium homeostasis, where it regulates a
      series of diverse cellular functions. A previous study indicated that CaSR is
      expressed in mouse glomerular mesangial cells (MCs), and stimulation of CaSR
      induces cell proliferation. However, the signaling cascades initiated by CaSR
      activation in MCs are currently unknown. In this study, our data demonstrate that
      CaSR mRNA and protein are expressed in a human mesangial cell line. Activating
      CaSR with high extracellular Ca2+ concentration ([Ca2+]o) or spermine induces a
      phospholipase C (PLC)-dependent increase in intracellular Ca2+ concentration
      ([Ca2+]i). Interestingly, the CaSR activation-induced increase in [Ca2+]i results
      not only from intracellular Ca2+ release from internal stores but also from
      canonical transient receptor potential (TRPC)-dependent Ca2+ influx. This
      increase in Ca2+ was attenuated by treatment with a nonselective TRPC channel
      blocker but not by treatment with a voltage-gated calcium blocker or Na+/Ca2+
      exchanger inhibitor. Furthermore, stimulation of CaSR by high [Ca2+]o enhanced
      the expression of TRPC3 and TRPC6 but not TRPC1 and TRPC4, and siRNA targeting
      TRPC3 and TRPC6 attenuated the CaSR activation-induced [Ca2+]i increase. Further
      experiments indicate that 1-oleoyl-2-acetyl-sn-glycerol (OAG), a known activator
      of receptor-operated calcium channels, significantly enhances the CaSR activation
      induced [Ca2+]i increase. Moreover, under conditions in which intracellular
      stores were already depleted with thapsigargin (TG), CaSR agonists also induced
      an increase in [Ca2+]i, suggesting that calcium influx stimulated by CaSR
      agonists does not require the release of calcium stores. Finally, our data
      indicate that pharmacological inhibition and knock down of TRPC3 and TRPC6
      attenuates the CaSR activation-induced cell proliferation in human MCs. With
      these data, we conclude that CaSR activation mediates Ca2+ influx and cell
      proliferation via TRPC3 and TRPC6 in human MCs. 

PMID- 24905091
TI  - Atg1 kinase organizes autophagosome formation by phosphorylating Atg9.
AB  - The conserved Ser/Thr kinase Atg1/ULK1 plays a crucial role in the regulation of
      autophagy. However, only very few Atg1 targets have been identified, impeding
      elucidation of the mechanisms by which Atg1 regulates autophagy. In our study, we
      determined the Saccharomyces cerevisiae Atg1 consensus phosphorylation sequence
      using a peptide array-based approach. Among proteins containing this sequence we
      identified Atg9, another essential component of the autophagic machinery. We
      showed that phosphorylation of Atg9 by Atg1 is required for phagophore
      elongation, shedding light on the mechanism by which Atg1 regulates early steps
      of autophagy. 

PMID- 24905093
TI  - Impact of pneumococcal conjugate vaccines on the incidence of pneumonia in
      hospitalized children after five years of its introduction in Uruguay.
AB  - BACKGROUND: Data on the burden of pneumococcal disease and the most frequent
      serotypes demonstrated that invasive disease and pneumonia were important
      manifestations affecting children under 5 years of age. Therefore, pneumococcal
      diseases prevention became a public health priority. Uruguay was the first Latin
      American country to incorporate PCV7 into its National Immunization Program. The
      aim of this study is to compare the incidence rates for hospitalized pneumonia in
      children from the pre PCV introduction period and the following five years of
      PCVs application in Uruguay. METHODS AND FINDINGS: Population-based surveillance
      of pneumonia hospitalization rates, in children, less than 14 years of age, had
      been performed prior pneumococcal vaccination, and continued following PCV7
      introduction and PCV13 replacement, using the same methodology. Hospitalized
      children with pneumonia were enrolled from January 1, 2009 through December 31st,
      2012. The study was carried out in an area with a population of 238,002
      inhabitants of whom 18, 055 were under five years of age. Patients with acute
      lower respiratory infections for whom a chest radiograph was performed on
      admission were eligible. Digitalized radiographs were interpreted by a reference
      radiologist, using WHO criteria. Pneumonia was confirmed in 2,697 patients, 1,267
      with consolidated and 1,430 with non consolidated pneumonia of which incidence
      decrease, between 2009 and 2012, was 27.3% and 46.4% respectively. 2001-2004 and
      2009-2012 comparison showed a significant difference of 20.4% for consolidated
      pneumonia hospitalizations. A significant incidence decline was recorded among
      children 6 to 35 months of age. CONCLUSIONS: An overall significant reduction in
      pneumonia hospitalizations was observed following the introduction of PCV7 and
      furthermore following the change to PCV13.

PMID- 24905092
TI  - Comparison of efficacy and safety of tenofovir and entecavir in chronic hepatitis
      B virus infection: a systematic review and meta-analysis.
AB  - OBJECTIVE: Tenofovir (TDF) and entecavir (ETV) are both potent antiviral agents
      for the treatment of chronic hepatitis B virus (HBV) infection. Multiple studies
      have compared efficacy and safety of these two agents, but yielded inconsistent
      results. Hence, we conducted a meta-analysis to discern comparative efficacy and
      safety. METHODS: Published data relevant to a comparison of TDF and ETV used in
      HBV were included. HBV DNA suppression rate, ALT normalization rate, and HBeAg
      seroconversion rate at 24 weeks and 48 weeks were reviewed. Drug safety profiles
      and resistance were also discussed. RESULTS: Seven articles met entry criteria.
      Four and six articles included data for 24 and 48-week HBV DNA suppression rates,
      respectively, and no significant differences for the rates between the two drugs
      were found in chronic HBV patients (TDF vs. ETV: relative risk [RR] = 1.10, 95%
      CI = 0.91-1.33 and RR = 1.07, 95% CI = 0.99-1.17 for 24 weeks and 48 weeks,
      respectively). For the ALT normalization rate (three studies for 24 weeks, four
      articles for 48 weeks) and HBeAg seroconversion rate (two and four studies for 24
      weeks and 48 weeks, respectively), no difference was observed between TDF and
      ETV. Additionally, no significant distinction in short term safety was found for
      CHB patients. CONCLUSIONS: TDF and ETV are similarly effective and safe in
      chronic HBV patients after 24 weeks and 48 weeks of anti-viral therapy.
      Nevertheless, the long-term efficacy and safety of TDF and ETV should be
      monitored in prolonged therapy.

PMID- 24905094
TI  - Can exercise capacity assessed by the 6 minute walk test predict the development
      of major adverse cardiac events in patients with STEMI after fibrinolysis?
AB  - BACKGROUND: To assess the added value of the 6 minute walk test distance (6MWTD)
      in the risk-stratification methods for patients with ST -segment elevation
      myocardial infarction (STEMI) treated with fibrinolysis. METHODOLOGY/PRINCIPAL
      FINDINGS: This is a prospective cohort study of one hundred consecutive patients
      with STEMI, who had received fibrinolysis, at Assuit University Hospital. All
      patients underwent 6MWT pre- discharge and were followed up for 3 months to
      monitor the incidence of major adverse cardiac events (MACE). Patients were
      divided into 3 groups according to the level of 6MWTD (level I>450 m, level II =
      300-450 m and level III<300 m). Among the study population, the median 6MWT
      distance was 370 meters (interquartile range 162-462). The mean age was 60.9+/
      10.7 years, 71.9% of them were males, 2/3 had anterior MI. only 10.5% had
      successful thrombolysis. Compared to patients in level I (>450 m), patients in
      level III (<300 m) were more likely to have clinical risk factors as
      hypertension, diabetes and impaired renal function. The patient's mean TIMI score
      was 3.4+/-2.2, the mean GRACE score was 150.5+/-27.7. There was a significant
      negative correlation between the 6 MWTD and GRACE risk score (r = -0.80,
      p<0.001). At 3 months of follow-up, 51% had MACE including 16% were dead.
      Multivariate logistic regression analysis identified that the GRACE risk score
      and 6MWT distance levels were the best predictors of the MACE at 3 month of
      follow up. The incidence of MACE was 4 times higher in patients with high GRACE
      risk score who couldn't walk more than 300 meters (OR = 4.66, 95% CI = 1.1-14.5,
      p = 0.006). CONCLUSIONS/SIGNIFICANCE: In patients with STEMI treated with
      fibrinolysis, the addition of 6MWTD assessment pre-discharge to the traditional
      GRACE risk score improved the risk prediction of cardiovascular events at 3 month
      follow up.

PMID- 24905095
TI  - Synaptonemal complex protein 3 is a prognostic marker in cervical cancer.
AB  - Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated
      in various cancer cells; however, its oncogenic potential and clinical
      significance has not yet been characterized. In the present study, we
      investigated the oncogenic role of SCP3 and its relationship with phosphorylated
      AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was
      investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3
      and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro
      and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181
      cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by
      immunohistochemistry and analyzed the correlation between SCP3 expression and
      clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT
      mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3
      cells demonstrated that the C-terminal region of human SCP3 is important for AKT
      activation and its oncogenic potential. High expression of SCP3 was significantly
      associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3
      expression was positively associated with pAKT protein level in cervical
      neoplasias. Survival times for patients with cervical cancer overexpressing both
      SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for
      patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as
      determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3
      plays an important role in the progression of cervical cancer through the AKT
      signaling pathway, supporting the possibility that SCP3 may be a promising novel
      cancer target for cervical cancer therapy. 

PMID- 24905098
TI  - CLOCK 3111 T/C SNP interacts with emotional eating behavior for weight-loss in a
      Mediterranean population.
AB  - OBJECTIVE: The goals of this research was (1) to analyze the role of emotional
      eating behavior on weight-loss progression during a 30-week weight-loss program
      in 1,272 individuals from a large Mediterranean population and (2) to test for
      interaction between CLOCK 3111 T/C SNP and emotional eating behavior on the
      effectiveness of the weight-loss program. DESIGN AND METHODS: A total of 1,272
      overweight and obese participants (BMI: 31+/-5 kg/m2), aged 20 to 65 years,
      attending outpatient weight-loss clinics were recruited for this analysis.
      Emotional eating behavior was assessed by the Emotional Eating Questionnaire
      (EEQ), a questionnaire validated for overweight and obese Spanish subjects.
      Anthropometric measures, dietary intake and weight-loss progression were assessed
      and analyzed throughout the 30-week program. Multivariate analysis and linear
      regression models were performed to test for gene-environment interaction.
      RESULTS: Weight-loss progression during the 30-week program differed
      significantly according to the degree of emotional eating behavior. Participants
      classified as 'very emotional eaters' experienced more irregular (P = 0.007)
      weight-loss, with a lower rate of weight decline (-0.002 vs. -0.003, P<0.05) in
      comparison with less emotional eaters. The percentage of weight-loss was also
      significantly higher in 'non-emotional eaters' (P = 0.009). Additionally, we
      identified a significant gene-environment interaction associated with weight-loss
      at the CLOCK 3111 T/C locus (P = 0.017). By dichotomizing the emotional eating
      behavior score, linear regression analysis indicated that minor C allele carriers
      with a high emotional score (> = 11), lost significantly less weight than those C
      carriers with a low emotional score (<11) (P = 0.005). CONCLUSIONS: Emotional
      eating behavior associates with weight-loss pattern, progression and total weight
      loss. Additionally, CLOCK 3111 T/C SNP interacts with emotional eating behavior
      to modulate total weight loss. These results suggest that the assessment of this
      locus and emotional eating behavior could improve the development of effective,
      long-tern weight-management interventions.

PMID- 24905099
TI  - Kineret(r)/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant
      Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus
      infection.
AB  - OBJECTIVES: Community-acquired Staphylococcus aureus necrotizing pneumonia is a
      life-threatening disease. Panton Valentine Leukocidin (PVL) has been associated
      with necrotizing pneumonia. PVL triggers inflammasome activation in human
      macrophages leading to IL-1beta release. IL-1beta activates lung epithelial cells
      to release IL-8. This study aimed to assess the relevance of this inflammatory
      cascade in vivo and to test the potential of an IL-1 receptor antagonist (IL
      1Ra/Kineret) to decrease inflammation-mediated lung injury. METHODS: We used the
      sequential instillation of Heat-killed S. aureus and PVL or S. aureus infection
      to trigger necrotizing pneumonia in rabbits. In these models, we investigated
      inflammation in the presence or absence of IL-1Ra/Kineret. RESULTS: We
      demonstrated that the presence of PVL was associated with IL-1beta and IL-8
      release in the lung. During PVL-mediated sterile pneumonia, Kineret/IL-1Ra
      reduced IL-8 production indicating the relevance of the PVL/IL-1/IL-8 cascade in
      vivo and the potential of Kineret/IL-1Ra to reduce lung inflammation. However,
      Kineret/IL-1Ra was ineffective in blocking IL-8 production during infection with
      S. aureus. Furthermore, treatment with Kineret increased the bacterial burden in
      the lung. CONCLUSIONS: Our data demonstrate PVL-dependent inflammasome activation
      during S.aureus pneumonia, indicate that IL-1 signaling controls bacterial burden
      in the lung and suggest that therapy aimed at targeting this pathway might be
      deleterious during pneumonia.

PMID- 24905100
TI  - Interaction of APOBEC3A with DNA assessed by atomic force microscopy.
AB  - The APOBEC3 family of DNA cytosine deaminases functions to block the spread of
      endogenous retroelements and retroviruses including HIV-1. Potency varies among
      family members depending on the type of parasitic substrate. APOBEC3A (A3A) is
      unique among the human enzymes in that it is expressed predominantly in myeloid
      lineage cell types, it is strongly induced by innate immune agonists such as type
      1 interferon, and it has the capacity to accommodate both normal and 5-methyl
      cytosine nucleobases. Here we apply atomic force microscopy (AFM) to characterize
      the interaction between A3A and single- and double-stranded DNA using a hybrid
      DNA approach in which a single-stranded region is flanked by defined length
      duplexes. AFM image analyses reveal A3A binding to single-stranded DNA, and that
      this interaction becomes most evident (~80% complex yield) at high protein-to-DNA
      ratios (at least 100?1). A3A is predominantly monomeric when bound to single
      stranded DNA, and it is also monomeric in solution at concentrations as high as
      50 nM. These properties agree well with recent, biochemical, biophysical, and
      structural studies. However, these characteristics contrast with those of the
      related enzyme APOBEC3G, which in similar assays can exist as a monomer but tends
      to form oligomers in a concentration-dependent manner. These AFM data indicate
      that A3A has intrinsic biophysical differences that distinguish it from APOBEC3G.
      The potential relationships between these properties and biological functions in
      innate immunity are discussed. 

PMID- 24905101
TI  - Old wine in new bottles: decanting systemic family process research in the era of
      evidence-based practice.
AB  - Social cybernetic (systemic) ideas from the early Family Process era, though
      emanating from qualitative clinical observation, have underappreciated heuristic
      potential for guiding quantitative empirical research on problem maintenance and
      change. The old conceptual wines we have attempted to repackage in new, science
      friendly bottles include ironic processes (when "solutions" maintain problems),
      symptom-system fit (when problems stabilize relationships), and communal coping
      (when we-ness helps people change). Both self-report and observational
      quantitative methods have been useful in tracking these phenomena, and together
      the three constructs inform a team-based family consultation approach to working
      with difficult health and behavior problems. In addition, a large-scale,
      quantitatively focused effectiveness trial of family therapy for adolescent drug
      abuse highlights the importance of treatment fidelity and qualitative approaches
      to examining it. In this sense, echoing the history of family therapy research,
      our experience with juxtaposing quantitative and qualitative methods has gone
      full circle-from qualitative to quantitative observation and back again. 

PMID- 24905102
TI  - Hyperhidrosis: review of recent advances and new therapeutic options for primary
      hyperhidrosis.
AB  - PURPOSE OF REVIEW: Primary focal hyperhidrosis is a common condition that
      negatively impacts quality of life for many pediatric patients and can be
      challenging to treat. Standard treatments for hyperhidrosis can be used with
      success in many patients, and newer therapies and techniques offer options that
      have demonstrated efficacy and safety. This review highlights standard therapies
      for primary focal hyperhidrosis as well as the most recent technique advancements
      and alternative treatment options. RECENT FINDINGS: The standard approach to
      treating primary focal hyperhidrosis remains initiation of topical preparations,
      followed by advancement to systemic medications, local administration of
      medication and/or surgical procedures. Recent studies focus on enhancing
      tolerability of topical preparations as well as evaluating the efficacy of
      neuromodulator injections, oral anticholinergic medications and laser therapy.
      Microwave technology has also been introduced for the treatment of focal
      hyperhidrosis with promising results. SUMMARY: Many therapies exist for
      hyperhidrosis, and each treatment plan must be evaluated on a patient-by-patient
      basis. Advances in standard therapies and emergence of new treatment techniques
      are the main emphases of current published literature on hyperhidrosis. This
      article presents recent therapeutic options as well as updates on more
      established strategies to help practitioners treat this challenging condition.

PMID- 24905103
TI  - IgG4 antibodies in autoimmune polyglandular disease and IgG4-related
      endocrinopathies: pathophysiology and clinical characteristics.
AB  - PURPOSE OF REVIEW: This review discusses the IgG4-related disease spectrum (IgG4
      RD), the autoimmune polyglandular syndromes (APS), the association of IgG4 with
      APS, and possible pathobiology. RECENT FINDINGS: IgG4-RD is a multiorgan
      autoimmune disorder characterized by fibrous inflammation, IgG4-positive plasma
      cell infiltration in affected tissues, and elevated serum concentrations of IgG4.
      IgG4-RD can affect any organ and has a heterogeneous presentation. Consensus
      criteria for diagnosis in specific organs have been established. The recognition
      and diagnosis of IgG4-RD are crucial because the disease responds favorably to
      immunosuppression (e.g., glucocorticoids, rituximab). The precise mechanisms
      leading to disease are unknown, but IgG4 antibodies may undergo a half antibody
      exchange, which renders them incapable of activating the complement pathway.
      SUMMARY: Despite significant advances in disease recognition and treatment
      strategies, the disorder remains poorly understood. The precise role of IgG4,
      whether it is protective or pathogenic, is still being debated.

PMID- 24905104
TI  - Role of growth factors in control of pancreatic beta cell mass: focus on
      betatrophin.
AB  - PURPOSE OF REVIEW: Betatrophin is a newly described hormone, which potently
      stimulates beta cell replication in mice. This discovery has engendered great
      hope that it could prove clinically important in the treatment of type 1 and type
      2 diabetes. RECENT FINDINGS: Betatrophin, a 198-amino acid protein secreted by
      liver and adipose tissue, stimulates growth of pancreatic beta cell mass in
      insulin-resistant mice. Betatrophin has previously been named RIFL, lipasin, and
      ANGPLT8, and its salutory effects on lipid metabolism have been described in
      mouse and human studies. Serum betatrophin levels in humans correlate with
      improved adipose tissue lipid storage and lower serum triglyceride levels in the
      fed state, but do not correlate with insulin resistance or carbohydrate tolerance
      in humans. Betatrophin has not yet been shown to have an effect on beta cell
      replication in human pancreatic islets. SUMMARY: Many endocrine and paracrine
      factors, of which betatrophin is the newest described, increase beta cell mass in
      murine models. None of these factors, including betatrophin, have displayed the
      same activity in clinical studies. This may reflect a profound species difference
      in beta cell regeneration pathways in mice and humans.

PMID- 24905105
TI  - The influence of affective empathy and autism spectrum traits on empathic
      accuracy.
AB  - Autism spectrum disorder is characterized by interpersonal deficits and has been
      associated with limited cognitive empathy, which includes perspective taking,
      theory of mind, and empathic accuracy (EA). The capacity for affective empathy
      may also be impaired. In the present study we aimed to determine if EA in
      normally developing individuals with varying levels of autism spectrum traits is
      moderated by trait affective empathy. Fifty male and fifty female participants
      ('perceivers') completed the Autism-Spectrum Quotient and the Balanced Emotional
      Empathy Scale to assess autism spectrum traits and trait affective empathy,
      respectively. EA was assessed using a Dutch-language version of a previously
      developed task and involved rating the feelings of others ('targets') verbally
      recounting autobiographical emotional events. Targets varied in trait emotional
      expressivity, assessed using the Berkeley Expressivity Questionnaire. Perceivers
      with more autism spectrum traits performed worse on the EA task, particularly
      when their trait affective empathy was relatively low. Interpersonal deficits in
      autism spectrum disorder may be partially explained by low cognitive empathy.
      Further, they might be aggravated by a limited capacity for affective empathy. 

PMID- 24905106
TI  - [Development of gastrointestinal infectious diseases between 2000 and 2012].
AB  - BACKGROUND: Infectious gastroenterological diseases are of increasing medical and
      health-economic significance. METHOD: To evaluate the development of
      gastroenterolgical infections (GI) over the past 10 years, we have analysed the
      published data of the German Federal Statistics Office on GI hospital admissions
      between 2001 and 2011 and the data on cases of infection reported to the Robert
      Koch Institute between 2001 and 2012. RESULTS: In 2011 520795 patients with
      infectious diarrhoea (ICD 10 A00-A09) required hospital admission. The number of
      coded main diagnoses alone has more than doubled from 127867 to 282199 cases per
      year. The increase in the group of over 65-year-old patients was particularly
      high. The highest increase among hospitalised patients was seen for Clostridium
      difficile infections (99779 cases in 2011) together with noro- and rotavirus
      infections, whereas the number of cases with salmonella declined. The number of
      hospital deaths related to infectious gastrointestinal diseases (major clinical
      diagnosis) rose from 401 in 2000 to 4152 in 2011. Particularly frequent were
      deaths coded under the ICD 10 diagnosis A04, which includes Clostridium difficile
      infections (CDI). DISCUSSION: In spite of the limitations due to differing data
      sources, reporting and recording rules, the analysed data do allow conclusions as
      to the development of the last 10 years. Gastrointestinal infections have not
      only markedly increased but also required increasing hospital capacities in
      gastroenterological departments. Since, with the exception of rotavirus
      infections, no vaccination strategies are available, these developments will have
      to be combatted above all by improved infectiological training for
      gastroenterologists.

PMID- 24905107
TI  - Prevalence of risk factors for liver disease in a random population sample in
      southern Germany.
AB  - BACKGROUND: Chronic liver disease leads to fibrosis and cirrhosis of the liver.
      This may, in turn, result in chronic liver failure or the development of
      hepatocellular carcinoma (HCC). Main risk factors for chronic liver disease are
      viral hepatitis and alcoholism. The present study assessed a randomly selected
      population in southern Germany for risk factors for chronic liver disease such as
      fatty liver disease, viral hepatis infection and life-style factors. In addition,
      the potential association with elevated liver enzymes was investigated. METHODS:
      A total of 2256 subjects (1182 females, 1074 males), aged 18 - 65 years,
      participated in the study. Each subject underwent a standardized ultrasound
      examination, and anthropometric and biochemical assessments. Test subjects were
      randomly selected from the general population of a town in southwestern Germany.
      Data were acquired from November to December 2002 without further follow-up.
      RESULTS: Several factors were found to be associated with chronic liver disease
      in the study population. Alcohol consumption >20 g/d was seen in 18.1% (n=409).
      Metabolic syndrome was diagnosed in 5.9% (n=132). The number of people with a BMI
      greater than 25 kg/m(2) was 45.1% (n=1017). The prevalence of subjects with
      chronic hepatitis B was 0.7% (n=15), that of anti-HCV positive patients,
      0.6%(n=15). Elevated gGT was seen in 10.4% (n=14) of the patients. Prevalence of
      hepatic steatosis was 25.0% (n=564). CONCLUSIONS: Many cases of chronic liver
      disease could be prevented by healthy nutrition, optimized medical treatment of
      associated disorders, and prevention strategies such as routine vaccination, in
      particular, against hepatitis B virus (HBV).

PMID- 24905108
TI  - Tacrolimus as a reasonable alternative in a patient with steroid-dependent and
      thiopurine-refractory autoimmune pancreatitis with IgG4-associated cholangitis.
AB  - BACKGROUND: More recently, autoimmune pancreatitis (AIP) in association with IgG4
      positive cholangitis (IAC) has been recognised as a new and challenging entity.
      Currently, initiation of high dose steroids (e.g., prednisolone 0.5 - 1
      mg/kg/day) followed by a steroid dose taper in combination with purine
      antagonists (e.g., azathioprine or 6-mercaptopurine) after resolution has been
      recommended as standard therapy. CASE REPORT: A 68-year-old male patient was
      referred to our institution in February 2012 for therapy evaluation of a steroid
      dependent course of autoimmune pancreatitis type 1 with IgG4-associated
      cholangitis. Since the first diagnosis in March 2011, the patient was treated
      with high-dose steroids with good response. Whenever steroids were tapered down
      to a daily dose <20 mg, cholestatic liver enzymes increased dramatically despite
      concurrent immunosuppressive therapy primarily with azathioprine and 6-MP
      thereafter. Therefore, we restarted steroid therapy (1 mg/kg/day) in combination
      with tacrolimus achieving a target level of 5 - 7 ng/mL. During the down-tapering
      phase, follow-up examinations presented a patient in good general condition
      without jaundice. Moreover, liver and pancreatic enzymes and also immunoglobulins
      returned to normal values without any evidence of relapse up today (66 weeks).
      CONCLUSION: In this case, the combination of steroids with tacrolimus seems to be
      a reasonable alternative in a patient with steroid-dependent and thiopurine
      refractory autoimmune pancreatitis with IgG4-associated cholangitis. To date,
      this is the first description of such a therapeutic approach for this entity.

PMID- 24905109
TI  - [Abdominal actinomycosis: a rare differential diagnosis to colon carcinoma and
      Morbus Crohn].
AB  - Abdominal actinomycosis is a rare, chronic and slowly progressive granulomatous
      disease. The clinical presentation of abdominal actinomycosis shows a great
      variability and it often mimics other intraabdominal pathologies like chronic
      inflammatory bowel diseases or malignancies. A correct diagnosis can rarely be
      established before radical surgery especially in patients with advanced tumors
      and an acute clinical presentation. Actinomyces are considered to be residential
      saprophytes in the gastroinstetinal tract and require a mucosal lesion to cause
      an opportunistic infection. Microbiological culture is the gold standard for
      diagnosis, despite high false-negative rates in daily routine testing. Therefore,
      actinomycosis is diagnosed more often histopathologically by detection of sulfur
      granules in the surgical specimen. The postoperative treatment of choice is
      intravenous followed by oral penicillin over a few weeks due to good response and
      low resistance rates. There are no evidence based recommendations concerning the
      duration of antibiotic treatment, but a treatment of at least 4 weeks depending
      on the clinical course is advisable to achieve permanent recovery. The following
      case report deals with a severe clinical course of an abdominal actinomycosis.
      The 49-year-old female patient had to be operated as an emergency under suspicion
      of an advanced colonic carcinoma with bowel obstruction. She needed an elaborate
      operative and postoperative therapy. 

PMID- 24905111
TI  - [Refeeding syndrome: a review of the literature].
AB  - The refeeding syndrome is a dangerous condition, which may even lead to death.
      The syndrome occurs after re-establishment of adequate nutrition in malnourished
      and cachectic patients. More specifically its occurrence has been reported during
      oral, enteral and parenteral feeding. Early diagnosis is crucial for adequate and
      timely therapy. However, due to a lack of knowledge in the community this is not
      always achieved. The leading symptom is hypophosphatemia, often accompanied by
      electrolyte disturbances and vitamin and trace element deficiencies. Due to a
      concomitant administration of carbohydrates and intravenous fluid volume it may
      also lead to hypervolemia with cardiac failure. Compromise of other organ
      functions with a varying degree of severity, even leading to death, have been
      reported. The most efficient prevention of the refeeding syndrom is recommended
      by an early identification of patients at risk and the administration of an
      initially lower caloric nutrition accompanied by a tight and regularly scheduled
      observation of relevant laboratory parameters. METHODS: This literature research
      included the following terms: "refeeding syndrome" and "hypophosphataemia"
      including the 2006 guidelines from the National Institute for Health and Clinical
      Excellence (UK).

PMID- 24905110
TI  - [Gastroenterology in the former GDR (1975-1990) and the changes after German
      reunification].
AB  - This short overview sketches the state of Gastroenterology in the GDR (1975 -
      1990) from the point of view of an East-German contemporary witness. The "Society
      for Gastroenterology/GDR" (GfG) has played a decisive role for the development of
      the Gastroenterology in the GDR. The society promoted medical education and
      constitutions of gastroenterological centers, fostered gastroenterological
      research and controlled the standards for the recognition of Gastroenterology as
      a state-accepted medical sub-discipline. An extensive program of scientific and
      educative events included two-annual meetings of scientific congresses, the
      "Berka-Talks", endoscopic workshops" and featured special symposia such as for
      Hepatology, Pancreatology and gastro-intestinal Microbiology. Temporary working
      groups developed technical and professional legal advice. Although the GfG was a
      full member of the respective international organizations (OMGE, ASNEMGE, ESGE),
      it was almost impossible building up reliable international contacts in a mutual
      interest. Especially, contacts with colleagues representing the "German Society
      of Digestion and Metabolic Diseases" (DGVS) were impeded. With the political
      changes of 1989/1990, an association of the two German Societies for
      Gastroenterology seemed within reach. At a meeting in Halle (Saale) (March, 22nd,
      1990), representatives of DGVS and GfG quickly agreed on modalities to merge the
      two societies. After the 45th meeting of the DGVS (October 3rd-6th, Essen) more
      than 600 GDR physicians could join the BRD society under accommodating
      conditions. The GfG had fulfilled its historical function as a "bridge" during
      the division of Germany with dignity and was suspended (November, 24nd,1990). 

PMID- 24905112
TI  - [Should We Look for Celiac Disease in Fibromyalgia/IBS Patients?].

PMID- 24905113
TI  - [Diagnosis of atypical reflux: new probe - more problems].

PMID- 24905114
TI  - [Position paper of the professional societies to apply recommendation of
      endoscopic biliodigestive diversion in Germany - DDG / DGAV / DGVS -].

PMID- 24905115
TI  - Ethyl 1,8-naphthyridone-3-carboxylates downregulate human papillomavirus-16 E6
      and E7 oncogene expression.
AB  - Strong epidemiological and molecular data associate cervical cancer (CC) with
      high-risk human papillomavirus (HPV) infections. The carcinogenic mechanism
      depends mainly on the expression of E6 and E7 oncoproteins encoded by the viral
      genome. Using a cell-based high-throughput assay, an in-house library of
      compounds was screened identifying the 1,8-naphthyridone 1 that efficiently
      inhibited the transcription driven by the long control region of the HPV genome.
      A series of analogues were then synthesized, obtaining more potent derivatives
      able to downregulate E6 and E7 transcripts in HPV-16-positive CC CaSki cells. An
      unusual structural insight emerged for the C-3 position of the 1,8-naphthyridone
      core, where the ethyl carboxylate esters, but not the carboxylic acids, are
      responsible for the activity. In vitro uptake studies showed that the 3-ethyl
      carboxylates do not act as prodrugs. The 1,8-naphthyridones emerged as valid
      starting points for the development of innovative agents potentially useful for
      the treatment of HPV-induced CC. 

PMID- 24905117
TI  - When in doubt about lab tests...

PMID- 24905118
TI  - Intimate partner violence: screen others, besides heterosexual women.

PMID- 24905116
TI  - A functional network perspective on response inhibition and attentional control.
AB  - Inferior frontal cortex (IFC) modules that inhibit dominant behaviours are a
      popular feature in theories of cognitive dysfunction. However, the paradigms on
      which these theories are based fail to distinguish between inhibitory and non
      inhibitory cognitive demands. Here we use four novel fMRI variants of the classic
      stop-signal task to test whether the IFC houses unique inhibitory modules. Our
      results demonstrate that IFC sub-regions are not functionally unique in their
      sensitivities to inhibitory cognitive demands, but instead form components of
      spatially distributed networks. These networks are most strongly activated when
      infrequent stimuli are being processed, regardless of behavioural inhibitory
      demands, and when novel tasks are being acquired, as opposed to when routine
      responses must be suppressed. We propose that there are no inhibitory modules
      within the frontal lobes and that behavioural inhibition is an emergent property
      of spatially distributed functional networks, each of which supports a broader
      class of cognitive demands. 

PMID- 24905119
TI  - A guide to better wound closures.

PMID- 24905120
TI  - Should you suspect the female athlete triad?

PMID- 24905121
TI  - Case review. Lemierre's syndrome.
AB  - A previously healthy 35-year-old man with a one-week history of left-sided neck
      pain and fever as high as 104 degrees F sought care at our emergency department.
      He was given a diagnosis of viral pharyngitis and discharged. He returned the
      next day and indicated that he was now experiencing drenching night sweats and
      weakness. 

PMID- 24905122
TI  - Pitfalls & pearls for 8 common lab tests.

PMID- 24905123
TI  - PURLs: Prolotherapy: a nontraditional approach to knee osteoarthritis.

PMID- 24905124
TI  - Adolescent with rash on face and scalp.

PMID- 24905125
TI  - Clinical inquiry: How can we effectively treat stress urinary incontinence
      without drugs or surgery?

PMID- 24905126
TI  - Clinical inquiry: How do hydrochlorothiazide and chlorthalidone compare for
      treating hypertension?

PMID- 24905127
TI  - Clinical inquiry: Which prophylactic therapies best prevent gout attacks?

PMID- 24905128
TI  - How to discuss sex with elderly patients.

PMID- 24905129
TI  - PURLs: Should you consider antibiotics for exacerbations of mild COPD?

PMID- 24905130
TI  - What you should know about patients who bring a list to their office visit.
AB  - PURPOSE: Little is known about patients who present a written list during a
      medical consultation.In this preliminary study, we sought to examine and
      characterize patients who use a prepared list. METHODS: The design was an open
      observational case-controlled study that took place at 2 urban primary care
      clinics. We enrolled patients consecutively as they arrived with a written list
      for consultation. Consecutive patients presenting without a list served as the
      control group. Physician interviews and completed questionnaires provided
      demographic and medical characteristics of this group and explanations for list
      preparation. RESULTS: Fifty-four patients presented with a list and were compared
      with controls. Statistically, patients arriving with a list were significantly
      more likely to be older and retired, and less likely to be salaried workers or
      housewives. These patients had more chronic diseases and consumed more long-term
      medications. They had a greater number of doctor visits in the past year compared
      with controls, and perceived an increase in memory loss. There were no
      differences between the groups in terms of psychiatric disease or personality
      disorders. CONCLUSIONS: Aside from certain demographic and health
      characteristics, patients who use written lists do not differ substantially from
      those who don't. They have no discernible ill intention, and the list serves as a
      memory aid to make the most of the visit.

PMID- 24905131
TI  - Impacted cerumen or something else?
AB  - Despite having a tick in his ear canal for more than a month, the patient was
      doing well. 

PMID- 24905132
TI  - Recognizing and managing concussion in school sport.
AB  - Every country around the world enjoys some sort of sport. The Olympics sees
      countries from all over the globe participate in elite sport, in both winter and
      summer competitions. Australia is widely known for cricket and rugby; America is
      known for baseball and gridiron football (among others). These sports are played
      at an elite level as well as beginners from early ages as young as 4 years in the
      backyard. Yet, it is also these sports that can deliver a ball at the speed of
      100 km/h (football), 105 km/h (baseball), 112 km/h (rugby), 150 km/h (cricket),
      and 211 km/h (soccer). This is the same force that a car collision can produce.
      That force eventually finds a target, and in some cases, unfortunately, it is a
      head. Damage to the brain is not only from the impact of the ball hitting its
      target but rather also the shearing forces of acceleration-deceleration injury
      that can cause extensive injuries. There has been much discussion of late
      regarding concussion in sport and the accumulative effects of head blows
      resulting in varying degrees of memory loss and dementia later in life. The media
      have been saturated with heightened awareness of chronic traumatic
      encephalopathy. This, however, is still being researched. It is true that each
      concussion compounds the one before, but rather than focus on the injury,
      managers/coaches and sporting codes should be focusing on the identification and
      proper management of a suspected concussion and the return-to-play protocols.
      This is especially important in our schools where growing brains need nurturing.
      Neuroscience nurses are at the forefront of educating school children, teachers,
      and coaches through partnering with local schools. This article will focus on
      concussion recognition and management in school sport. 

PMID- 24905133
TI  - Facile synthesis of graphite/PEDOT/MnO2 composites on commercial supercapacitor
      separator membranes as flexible and high-performance supercapacitor electrodes.
AB  - A facile and low-cost method is presented to synthesize graphite/PEDOT/MnO2
      composites with controlled network structures on commercial supercapacitor
      separator (CSS) membranes for high-performance supercapacitors, in which pencil
      lead and a cellulose-based commercial supercapacitor separator membrane were
      applied as the graphite source and the flexible substrate, respectively. The
      dependence of PEDOT and MnO2 loading on the structural formation, the
      electrochemical performance of the hybrid electrode, and the formation mechanism
      of MnO2 nanowires are systematically investigated. The optimized electrode
      possesses a high areal capacitance of 316.4 mF/cm(2) at a scan rate of 10 mV/s
      and specific capacitance of 195.7 F/g at 0.5 A/g. The asymmetric supercapacitor
      device assembled using optimized CSS/Graphite/PEDOT/MnO2 electrode and activated
      carbon electrode exhibits a high energy density of 31.4 Wh/kg at a power density
      of 90 W/kg and maintains 1 Wh/kg at 4500 W/kg. After 2000 cycles, the device
      retains 81.1% of initial specific capacitance, and can drive a mini DC-motor for
      ca. 10 s. The enhanced capability of the CSS-based graphite/PEDOT/MnO2 network
      electrode has high potential for low-cost, high-performance, and flexible
      supercapacitors. 

PMID- 24905134
TI  - A prospective randomized controlled trial comparing N-butyl-2 cyanoacrylate
      (Histoacryl), octyl cyanoacrylate (Dermabond), and subcuticular suture for
      closure of surgical incisions.
AB  - INTRODUCTION: The use of tissue adhesives for the closure of surgical incisions
      is increasing. Few studies directly compare tissue adhesives to one another or
      focus on the difference in wound closure time between tissue adhesives. We
      compared the use of N-butyl-2 cyanoacrylate (Histoacryl), octyl cyanoacrylate
      (Dermabond), or subcuticular suture in incisions resulting from reduction
      mammoplasty, mastopexy, panniculectomy, and abdominoplasty. METHODS: A 2-armed
      prospective randomized controlled trial was performed. Part 1 compared closure of
      surgical incisions with N-butyl-2 cyanoacrylate and octyl cyanoacrylate. Part 2
      compared the closure of surgical incisions with N-butyl-2 cyanoacrylate and
      subcuticular suture. End points were closure time, scar width, and satisfaction
      ratings. RESULTS: Both study arms revealed significantly faster closer times with
      N-butyl-2 cyanoacrylate [9/10 in part 1 (P = 0.022) and 10/10 in part 2 (P =
      0.002)]. Scar width difference did not reach statistical significance, and there
      was no difference in surgeon, independent reviewer, or patient satisfaction among
      the materials. CONCLUSIONS: Our results demonstrate a decreased time required for
      wound closure using N-butyl-2 cyanoacrylate compared to both suture and octyl
      cyanoacrylate regardless of incision type with no significant difference in scar
      width or satisfaction ratings.

PMID- 24905135
TI  - A Subcutaneous Alar Base (SCAB) flap to restore symmetry of the ala in primary
      cleft-lip nose repair.
AB  - Primary surgical correction of cleft-lip nose deformity is now well accepted.
      Despite various surgical techniques proposed, perfect nasal symmetry has not been
      persistently attained. The main reason is that the maxillary deficiency is
      frequently overlooked.This paper presents 62 cases of unilateral cleft lip
      repaired over the last 20 years by using the author's modification of the Millard
      primary lip nose repair. Each of these patients had a minimum follow-up of 1 year
      (range 1-12 years).The technique consists of raising a small subcutaneous alar
      base flap (SCAB) from the nasolabial region. The flap is turned over like a book
      page to add bulk to the deficient maxilla and to elevate the depressed ala. It
      also controls alar rotation and permits its permanent fixation to the anterior
      nasal spine.The results show that this modification has improved the alar contour
      and symmetry in patients undergoing primary cleft-lip nasal repair. There was
      minimal increase in the operating time and the final scar is similar to the
      original Millard technique. 

PMID- 24905136
TI  - The complete mitochondrial genome of the Border Collie dog.
AB  - Border Collie dog is one of the famous breed of dog. In the present work we
      report the complete mitochondrial genome sequence of Border Collie dog for the
      first time. The total length of the mitogenome was 16,730 bp with the base
      composition of 31.6% for A, 28.7% for T, 25.5% for C, and 14.2% for G and an A-T
      (60.3%)-rich feature was detected. It harbored 13 protein-coding genes, two
      ribosomal RNA genes, 22 transfer RNA genes and one non-coding control region (D
      loop region). The arrangement of all genes was identical to the typical
      mitochondrial genomes of dogs.

PMID- 24905137
TI  - Treatment of both native and deamidated gluten peptides with an endo-peptidase
      from Aspergillus niger prevents stimulation of gut-derived gluten-reactive T
      cells from either children or adults with celiac disease.
AB  - Celiac disease (CD) is characterized by an inappropriate immunological reaction
      against gluten driven by gluten-specific CD4+ T cells. We screened 25 proteases
      and tested 10 for their potential to degrade gluten in vitro. Five proteases were
      further tested for their ability to prevent the proliferative response by a
      gluten-specific CD4+ T cell clone and seven gluten-reactive T cell lines to
      protease-digested gluten peptides. A proline-specific endo-peptidase from
      Aspergillus niger (AnP2) was particularly efficient at diminishing proliferation
      after stimulation with cleaved antigen, and could completely block the response
      against both native and deamidated gluten peptides. We found that AnP2 was
      efficient down to a 1:64 protease:substrate ratio (w:w). When AnP2 was tested in
      assays using seven gluten-reactive T cell lines from individual CD patients
      (three adults and four children), the response to gluten was diminished in all
      cases. Our study indicates a therapeutic benefit of AnP2 to CD patients. 

PMID- 24905138
TI  - Orosomucoid secretion levels by epicardial adipose tissue as possible indicator
      of endothelial dysfunction in diabetes mellitus or inflammation in coronary
      artery disease.
AB  - OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with fat and autonomic
      system dysfunction. Epicardial adipose tissue (EAT) plays an endocrine role over
      the heart. Since orosomucoid (ORM) has local actions around the coronaries, our
      aim was to assess the relationship between its secretion profile by EAT and its
      catecholaminergic regulation in patients with T2DM and coronary artery disease
      (CAD). METHODS: We obtained EAT, subcutaneous adipose tissue (SAT) and plasma
      from 55 patients undergoing cardiac surgery. Fat explants were stimulated with
      isoproterenol (ISO) 1 MUM for 6 h. After, the fat explants released-ORM and
      plasma levels were analyzed by ELISA. mRNA or protein expression was analyzed by
      real time PCR or western blot, respectively. The effects of ORM on endothelial
      cells were analyzed by impedance and wound healing assays. RESULTS: We observed
      that EAT-released ORM levels were higher than SAT (328 +/- 185 vs 58 +/- 45
      ng/mL; p < 0.001). Interestingly, EAT secretion was lower in patients with than
      those without T2DM (260 +/- 141 vs 370 +/- 194 ng/mL; p < 0.05) and this
      difference was enhanced after ISO stimulation (p < 0.01). However, plasma levels
      (412 +/- 119 vs 594 +/- 207 MUg/mL) and EAT-released ORM levels were higher in
      patients with than those without CAD (384 +/- 195 vs 279 +/- 159 ng/mL; p <
      0.05). ISO stimulation, also reduced the EAT released-ORM levels in patients with
      CAD. On human endothelial cells, ORM induced an increase of healing and
      proliferation in a dose-dependent manner. CONCLUSION: EAT-released ORM levels in
      patients with T2DM or CAD and its regulation by catecholamines might be the
      mirror of local endothelium dysfunction or inflammatory process in different
      cardiovascular disorders.

PMID- 24905139
TI  - Relationship between plasma apelin level and coronary collateral circulation.
AB  - OBJECTIVE: Coronary collaterals play a crucial role during an acute ischemic
      attack. Angiogenesis has an important role in the formation of coronary
      collateral vessels. Previously, it was shown that apelin is a potential
      angiogenetic factor. Thus, we aimed to investigate relationship between plasma
      apelin levels and coronary collateral circulation in patients with stable
      coronary artery disease. METHODS: Among patients who underwent coronary
      angiography with stable angina pectoris, patients with a stenosis of >=90% were
      included in our study. Collateral degree was graded according to Rentrop-Cohen
      classification. Patients with grade 2 or 3 collateral degree were included in
      good collateral group and patients with grade 0 or 1 collateral degree were
      included in poor collateral group. RESULTS: Plasma apelin level was significantly
      higher in good collateral group (0.69 +/- 0.2 vs 0.59 +/- 0.2 ng/dl, p < 0.001).
      Serum nitric oxide levels were similar between two groups. In multivariate
      regression analysis apelin [6.95 (1.46-33.15), p = 0.015] and presence of total
      occlusion [4.40 (1.04-18.62), p = 0.044] remained as independent predictors for
      good coronary collateral development. CONCLUSIONS: Higher plasma apelin level was
      related to better coronary collateral development. Demonstration of favorable
      affects of apelin on good collateral development may lead to consider apelin in
      antiischemic treatment strategies in order to increase collateral development.

PMID- 24905140
TI  - Naringenin (NAR) and 8-prenylnaringenin (8-PN) reduce the developmental
      competence of porcine oocytes in vitro.
AB  - Flavanones such as naringenin (NAR) and 8-prenylnaringenin (8-PN) are
      increasingly used as dietary supplements despite scientific concern regarding
      adverse effects on female reproduction upon excessive intake. In the present
      study, NAR and 8-PN (0.3-1MUM) significantly affected porcine oocyte maturation
      in vitro by decreasing cumulus expansion. In addition, NAR and 8-PN decreased
      percentages of meiotic spindle formation, oocyte cleavage and blastocyst
      formation. The effects of NAR and 8-PN were different from estradiol (3.12MUM)
      induced effects. Still, the flavanone-induced effects were observed at
      concentrations that can be found in human plasma upon supplement intake and that
      resemble physiological estrogen equivalence levels in follicular fluids.
      Considering that abnormal oocyte maturation can cause subfertility, our study
      warrants that precautions are in place and excessive intake of NAR and 8-PN e.g.
      via dietary supplements should be avoided by women. 

PMID- 24905141
TI  - Aqueous (99)Tc, (129)I and (137)Cs removal from contaminated groundwater and
      sediments using highly effective low-cost sorbents.
AB  - Technetium-99 ((99)Tc), iodine-129 ((129)I), and cesium-137 ((137)Cs) are among
      the key risk-drivers for environmental cleanup. Immobilizing these radionuclides,
      especially TcO4(-) and I(-), has been challenging. TcO4(-) and I(-) bind very
      weakly to most sediments, such that distribution coefficients (Kd values;
      radionuclide concentration ratio of solids to liquids) are typically <2 mL/g;
      while Cs sorbs somewhat more strongly (Kd ~ 50 mL/g). The objective of this
      laboratory study was to evaluate 13 cost-effective sorbents for TcO4(-), I(-),
      and Cs(+) uptake from contaminated groundwater and sediments. Two organoclays
      sorbed large amounts of TcO4(-) (Kd > 1 * 10(5) mL/g), I(-) (Kd >= 1 * 10(4)
      mL/g), and Cs(+) (Kd > 1 * 10(3) mL/g) and also demonstrated a largely
      irreversible binding of the radionuclides. Activated carbon GAC 830 was effective
      at sorbing TcO4(-) (Kd > 1 * 10(5) mL/g) and I(-) (Kd = 6.9 * 10(3) mL/g), while
      a surfactant modified chabazite was effective at sorbing TcO4(-) (Kd > 2.5 *
      10(4) mL/g) and Cs(+) (Kd > 6.5 * 10(3) mL/g). Several sorbents were effective
      for only one radionuclide, e.g., modified zeolite Y had TcO4(-)Kd > 2.3 * 10(5)
      mL/g, AgS had I(-) Kd = 2.5 * 10(4) mL/g, and illite, chabazite, surfactant
      modified clinoptilolite, and thiol-SAMMS had Cs(+)Kd > 10(3) mL/g. These low-cost
      and high capacity sorbents may provide a sustainable solution for environmental
      remediation. 

PMID- 24905142
TI  - Associations between xerostomia, histopathological alterations, and autonomic
      innervation of labial salivary glands in men in late midlife.
AB  - OBJECTIVE: One aim of the present study was to investigate whether symptoms of
      oral dryness (xerostomia) during daytime, assessed in a study group of middle
      aged male positive and negative outliers in cognition scores, were associated
      with age-related degenerative changes in human labial salivary glands and with
      quantitative measures of the glandular autonomic innervation. Another aim was to
      study the relation between the autonomic innervation and loss of secretory acinar
      cells in these glands. METHODS: Labial salivary gland biopsies were taken from
      the lower lip from 190 men, born in 1953 and members of the Danish Metropolit
      birth cohort, who were examined for age-related changes in cognitive function and
      dental health as part of the Copenhagen University Center for Healthy Aging
      clinical neuroscience project. The glands were routinely processed and semi
      quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte
      infiltration. Sections of labial salivary gland tissue were stained with the
      panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic
      innervation of the glands was analyzed quantitatively by use of stereology.
      RESULTS: Labial salivary gland tissue samples from 33% of all participants
      displayed moderate to severe acinar atrophy and fibrosis (31%). Xerostomia was
      not significantly associated with structural changes of labial salivary glands,
      but in the subsample it was inversely related to the total nerve length in the
      glandular connective tissue. Acinar atrophy and fibrosis were negatively
      correlated with the parenchymal innervation and positively related to diffuse
      inflammation. CONCLUSIONS: The results from the present study indicate that
      aspects of the autonomic innervation of labial salivary glands may play a role in
      the occurrence of xerostomia which in the present study group was not
      significantly associated with degenerative changes in these glands. The findings
      further indicate that the integrity of labial salivary gland acini is related to
      the parenchymal autonomic innervation, whereas inflammatory processes may
      compromise it by alternative mechanisms.

PMID- 24905143
TI  - Electrical properties of human skin as aging biomarkers.
AB  - A non-invasive bioimpedance spectroscopy (BIS) and Cole-Cole impedance model
      parameters (R0, Rinfinity, tau and alpha) were used to analyze electrical
      properties of intact and stripped human skin for both gender subjects divided
      into younger and older age groups. R0, Rinfinity and tau significantly increased
      while alpha significantly decreased with age in stripped skin for both genders
      (p<0.031). Using pooled data with respect to age, gender and skin stripping, R0,
      Rinfinity and tau values were shown to increase with age (p<0.0034), R0, tau and
      alpha were different between genders (p<0.024) and R0, Rinfinity and tau
      decreased with skin stripping (p<0.000008). All of four Cole-Cole parameters were
      age dependent with specific differences observed for genders and intact and
      stripped skin layers. Therefore, Cole-Cole parameters, obtained by non-invasive
      BIS measurements, are a new type of age dependent biomarkers. 

PMID- 24905144
TI  - Pharmacological evaluation of the anxiolytic-like effects of EMD 386088, a
      partial 5-HT6 receptor agonist, in the rat elevated plus-maze and Vogel conflict
      tests.
AB  - The 5-HT6 is one of the most recent additions to the 5-HT receptor family. Its
      pharmacological profile and anatomical distribution is suggestive of a putative
      role in mood disorders. Most of preclinical evidence suggests an anxiolytic-like
      action of 5-HT6 receptor antagonists. Evaluation the anxiolytic-like effects of
      EMD 386088, a partial 5-HT6receptor agonist, and its putative mechanism of action
      in rats. EMD 386088, administered intraperitoneally at a dose of 2.5 mg/kg evoked
      specific anxiolytic-like activity in the automated version of the conflict
      drinking Vogel and the elevated plus-maze tests visible by increasing all
      parameters indicating a potential anti-anxiety effect. Its activity was blocked
      by the selective 5-HT6 receptor antagonist SB 271046, but not by the selective
      GABAA/benzodiazepine receptor antagonist flumazenil. EMD 386088 did not intensify
      an anxiolytic-like effect produced by diazepam in the elevated plus-maze test.
      These findings suggest that EMD 386088, a 5-HT6 receptor agonist, produces
      anxiolytic-like activity after systemic administration which may result from
      direct stimulation of 5-HT6 receptors. 

PMID- 24905145
TI  - Low-level gamma-ray spectrometry at the underground laboratory Garching.
AB  - Two low-background setups for material screening based on HPGe detectors were
      built in the Garching Underground Laboratory with an overburden of ~10 m.w.e.
      They include several layers of passive shielding as well as an active muon veto.
      The first setup (GEM) comprises a 150% efficiency HPGe detector which can
      optionally be surrounded by a NaI(Tl) scintillation detector that serves as anti
      Compton veto. The second setup (LoAx) consists of two smaller HPGe detectors
      which are arranged face-to-face to cover a larger solid angle around the sample
      and to allow coincidence measurements. For a 5.6 kg piece of copper after 11 days
      of measurement we have reached a sensitivity for (226)Ra and (228)Ra/(228)Th of
      ~5 mBq kg(-1) with the GEM setup. In the LoAx setup we have achieved limits of
      less than 100 mBq kg(-1) for (234)Th and (210)Pb with a 156 g sample of PPO
      wavelength shifter after 18 days of measurement.

PMID- 24905146
TI  - Whole genome sequence of Clostridium bornimense strain M2/40 isolated from a lab
      scale mesophilic two-phase biogas reactor digesting maize silage and wheat straw.
AB  - The bacterium Clostridium bornimense M2/40 is a mesophilic, anaerobic bacterium
      isolated from a two-phase biogas reactor continuously fed with maize silage and
      5% wheat straw. Grown on glucose, it produced H2, CO2, formiate, lactate and
      propionate as the main fermentation products, of which some compounds serve as
      substrates for methanogenic Archaea to form methane. Here, the whole genome
      sequence of the bacterium consisting of two circular replicons is reported. This
      genome information provides the basis for further studies addressing metabolic
      features of the isolate and its role in anaerobic biomass degradation. 

PMID- 24905147
TI  - Interaction of 2-oxoglutarate dehydrogenase OdhA with its inhibitor OdhI in
      Corynebacterium glutamicum: Mutants and a model.
AB  - Pyruvate dehydrogenase and oxoglutarate dehydrogenase catalyze key reactions in
      central metabolism. In Corynebacterium glutamicum and related bacteria like
      Mycobacterium tuberculosis both activities reside in a novel protein supercomplex
      with the fusion protein OdhA catalyzing the conversion of oxoglutarate to
      succinyl-coenzyme A. This activity is inhibited by the forkhead-associated (FHA)
      domain of the small autoinhibitory protein OdhI. Here we used a biological screen
      which enabled us to isolate suppressor mutants that are influenced in OdhA-OdhI
      interaction. Five mutants carrying an OdhI mutation were isolated and one with an
      OdhA mutation. The OdhA mutein OdhA-C704E and three additional C704 variants were
      constructed. They exhibited unaltered or even slightly enhanced OdhA activity but
      showed reduced inhibition and interaction with OdhI. The FHA domain of OdhI was
      crystallized and its structure found in full agreement with previously determined
      NMR structures. Based on further structural studies, OdhA-OdhI crosslinking
      experiments, and modeling we discuss the experimental data generated on OdhA-OdhI
      interaction, with the latter protein representing a rare example of an FHA domain
      also recognizing a non-phosphorylated interaction partner. 

PMID- 24905148
TI  - Expression of an evolved engineered variant of a bacterial glycine oxidase leads
      to glyphosate resistance in alfalfa.
AB  - The main strategy for resistance to the herbicide glyphosate in plants is the
      overexpression of an herbicide insensitive, bacterial 5-enolpyruvylshikimate-3
      phosphate synthase (EPSPS). A glyphosate resistance strategy based on the ability
      to degrade the herbicide can be useful to reduce glyphosate phytotoxicity to the
      crops. Here we present the characterization of glyphosate resistance in
      transgenic alfalfa (Medicago sativa L.) expressing a plant-optimized variant of
      glycine oxidase (GO) from Bacillus subtilis, evolved in vitro by a protein
      engineering approach to efficiently degrade glyphosate. Two constructs were used,
      one with (GO(TP+)) and one without (GO(TP-)) the pea rbcS plastid transit
      peptide. Molecular and biochemical analyses confirmed the stable integration of
      the transgene and the correct localization of the plastid-imported GO protein.
      Transgenic alfalfa plants were tested for glyphosate resistance both in vitro and
      in vivo. Two GO(TP+) lines showed moderate resistance to the herbicide in both
      conditions. Optimization of expression of this GO variant may allow to attain
      sufficient field resistance to glyphosate herbicides, thus providing a resistance
      strategy based on herbicide degradation. 

PMID- 24905149
TI  - Engineering of cyanobacteria for the photosynthetic production of limonene from
      CO2.
AB  - Isoprenoids, major secondary metabolites in many organisms, are utilized in
      various applications. We constructed a model photosynthetic production system for
      limonene, a volatile isoprenoid, using a unicellular cyanobacterium that
      expresses the plant limonene synthase. This system produces limonene
      photosynthetically at a nearly constant rate and that can be efficiently
      recovered using a gas-stripping method. This production does not affect the
      growth of the cyanobacteria and is markedly enhanced by overexpression of three
      enzymes in the intrinsic pathway to provide the precursor of limonene, geranyl
      pyrophosphate. The photosynthetic production of limonene in our system is more or
      less sustained from the linear to stationary phase of cyanobacterial growth for
      up to 1 month. 

PMID- 24905150
TI  - Evaluating the utility of hexapod species for calculating a confidence interval
      about a succession based postmortem interval estimate.
AB  - Carrion insect succession patterns have long been used to estimate the postmortem
      interval (PMI) during a death investigation. However, no published carrion
      succession study included sufficient replication to calculate a confidence
      interval about a PMI estimate based on occurrence data. We exposed 53 pig
      carcasses (16+/-2.5 kg), near the likely minimum needed for such statistical
      analysis, at a site in north-central Indiana, USA, over three consecutive summer
      seasons. Insects and Collembola were sampled daily from each carcass for a total
      of 14 days, by this time each was skeletonized. The criteria for judging a life
      stage of a given species to be potentially useful for succession-based PMI
      estimation were (1) nonreoccurrence (observed during a single period of presence
      on a corpse), and (2) found in a sufficiently large proportion of carcasses to
      support a PMI confidence interval. For this data set that proportion threshold is
      45/53. Of the 266 species collected and identified, none was nonreoccuring in
      that each showed at least a gap of one day on a single carcass. If the definition
      of nonreoccurrence is relaxed to include such a single one-day gap the larval
      forms of Necrophilaamericana, Fanniascalaris, Cochliomyia macellaria,
      Phormiaregina, and Luciliaillustris satisfied these two criteria. Adults of
      Creophilus maxillosus, Necrobiaruficollis, and Necrodessurinamensis were common
      and showed only a few, single-day gaps in occurrence. C.maxillosus, P.regina, and
      L.illustris displayed exceptional forensic utility in that they were observed on
      every carcass. Although these observations were made at a single site during one
      season of the year, the species we found to be useful have large geographic
      ranges. We suggest that future carrion insect succession research focus only on a
      limited set of species with high potential forensic utility so as to reduce
      sample effort per carcass and thereby enable increased experimental replication. 

PMID- 24905151
TI  - Development of a GC-MS method for methamphetamine detection in Calliphora
      vomitoria L. (Diptera: Calliphoridae).
AB  - Entomotoxicology is the study of using insects for the detection of drugs and
      other chemical substances in decomposing tissues. One research aspect in
      particular is the effects of these substances on arthropod development and
      morphology, and their consequences on the post mortem interval estimation. Since
      methamphetamine (MA) is becoming commonplace as an illegal recreational drug, a
      GC-MS method for the detection of MA in Calliphora vomitoria L. (Diptera:
      Calliphoridae) was developed and validated. Furthermore, the effect of MA on the
      development, growth rates and survival of the blowfly was investigated. Larvae
      were reared on liver substrates homogeneously spiked with measured amounts of MA
      (5 ng/g and 10 ng/g) based on typical concentrations found in human tissue in
      cases of death caused by MA overdose. The experimental results demonstrated that
      (i) MA produced a significant increase in the developmental time from egg to
      adult in C. vomitoria, (ii) approximately 60% of larvae exposed to either dose of
      MA died during the pupation period and (iii) the resultant lengths of larvae and
      pupae were on average significantly larger than the controls.

PMID- 24905152
TI  - Effects of methamphetamine and its primary human metabolite, p
      hydroxymethamphetamine, on the development of the Australian blowfly Calliphora
      stygia.
AB  - The larvae of necrophagous fly species are used as forensic tools for the
      determination of the minimum postmortem interval (PMI). However, any ingested
      drugs in corpses may affect larval development, thus leading to incorrect
      estimates of the period of infestation. This study investigated the effects of
      methamphetamine and its metabolite, p-hydroxymethamphetamine, on the forensically
      important Australian blowfly Calliphora stygia. It was found that the presence of
      the drugs significantly accelerated larval growth and increased the size of all
      life stages. Furthermore, drug-exposed samples remained as pupae for up to 78 h
      longer than controls. These findings suggest that estimates of the minimum PMI of
      methamphetamine-dosed corpses could be incorrect if the altered growth of C.
      stygia is not considered. Different temperatures, drug concentrations and
      substrate types are also likely to affect the development of this blowfly.
      Pending further research, the application of C. stygia to the entomological
      analysis of methamphetamine-related fatalities should be appropriately qualified.

PMID- 24905153
TI  - Postmortem volumetric CT data analysis of pulmonary air/gas content with regard
      to the cause of death for investigating terminal respiratory function in forensic
      autopsy.
AB  - Postmortem CT (PMCT) is useful to investigate air/gas distribution and content in
      body cavities and viscera. The present study investigated the procedure to
      estimate total lung air/gas content and aeration ratio as possible indices of
      terminal respiratory function, using three-dimensional (3-D) PMCT data analysis
      of forensic autopsy cases without putrefactive gas formation (within 3 days
      postmortem, n=75), and analyzed the volumetric data with regard to the cause of
      death. When 3-D bilateral lung images were reconstructed using an image analyzer,
      combined lung volume was larger in drowning (n=12) than in alcohol/sedative
      hypnotic intoxication (n=8) and sudden cardiac death (SCD; n=10), and
      intermediate in other cases, including mechanical asphyxiation (n=12), fire
      fatalities due to burns (n=6) and carbon monoxide intoxication (n=7), fatal
      methamphetamine abuse (n=7), hyperthermia (heatstroke; n=6) and fatal hypothermia
      (cold exposure; n=7). Air/gas content of the lung as detected using HU interval
      between -2000 and -400 ('effective' lung aeration areas) and between -2000 and 
      191 (total lung aeration areas) as well as the ratios to total lung volume
      ('effective' and total lung aeration ratios, respectively) was higher in
      mechanical asphyxiation, drowning, fatal burns and hypothermia (cold exposure)
      than in SCD, and was intermediate in other cases. 'Effective' and total lung
      aeration ratios may be useful for comparisons between specific causes of death to
      discriminate between hypothermia (cold exposure) and drug intoxication, and
      between SCD and other causes of death, respectively. These findings provide
      interesting insights into potential efficacy of PMCT data analyses of lung volume
      and CT density as well as lung air/gas content and aeration ratio with regard to
      the cause of death, as possible indicators of terminal respiratory function, as
      part of virtual autopsy of the viscera in situ. 

PMID- 24905154
TI  - A primer on the phylogeography of Lagothrix lagotricha (sensu Fooden) in northern
      South America.
AB  - The taxonomic history of the genus Lagothrix is complex, with molecular and
      morphological assessments giving conflicting results for the separation between
      its taxa. Phylogeographic studies of the most widely distributed species,
      Lagothrix lagotricha, have only been attempted recently and are limited to few
      individuals per collection site, many of which were captive making their
      geographical origin dubious. There is debate regarding the possibility of raising
      subspecies of Lagothrix lagotricha to the species level, therefore the
      geographical origin of samples is particularly relevant. In the present work we
      revisit the intraspecific phylogeography of L. lagotricha from northwestern South
      America, including the subspecies L. l. poeppiggi, L. l. lagotricha and L. l.
      lugens (sensu Fooden, 1963), using DNA sequence data from hypervariable region I
      of the mitochondrial control region (D-loop HVI). Our results suggest a complex
      picture in which there are well delimited evolutionary units that, nonetheless,
      do not correlate well with the morphological variation used to support the
      current delimitation of taxa. Additionally, we corroborate previous results
      showing a lack of reciprocal monophyly between the putative subspecies of
      Lagothrix lagotricha, and we propose that this may be due to ancestral
      polymorphism that has been maintained following the recent spread of woolly
      monkeys throughout the western Amazonian lowlands and into the inter-Andean
      region of Colombia. 

PMID- 24905155
TI  - Keeping score.

PMID- 24905156
TI  - Lost in transition: dynamic enhancer organization across naive and primed stem
      cell states.
AB  - Pluripotent stem cells transition between distinct naive and primed states that
      are controlled by overlapping sets of master regulatory transcription factors. In
      this issue of Cell Stem Cell, Buecker et al. (2014) and Factor et al. (2014)
      demonstrate that alternate enhancer usage, regulated by state-specific binding
      partners of master regulators, defines these pluripotent state transitions.

PMID- 24905157
TI  - Disease progression in myelodysplastic syndromes: do mesenchymal cells pave the
      way?
AB  - Early events driving the initiation and evolution of neoplasms remain poorly
      defined but involvement of an instructive or permissive niche has been
      implicated. In this issue of Cell Stem Cell, Medyouf et al. (2014) provide
      insights into the role of the niche in myelodysplastic syndromes, the principle
      preleukemic disorder of the hematopoietic system.

PMID- 24905158
TI  - Common ground: stem cell approaches find shared pathways underlying ALS.
AB  - The development of curative therapies for genetically complex diseases such as
      ALS has been delayed by the lack of relevant disease models. Recent advances
      using induced-pluripotent-stem-cell-derived motoneurons from patients harboring
      distinct ALS mutations have recapitulated essential disease features and have
      identified some common pathways driving disease pathogenesis.

PMID- 24905159
TI  - Human somatic cell nuclear transfer is alive and well.
AB  - In this issue, Chung et al. (2014) generate human embryonic stem cells by fusing
      an adult somatic cell to a previously enucleated human oocyte, in agreement with
      recent reports by the Mitalipov and Egli groups. We can now safely say that human
      somatic cell nuclear transfer is alive and well.

PMID- 24905160
TI  - Stem cells go soft: pliant substrate surfaces enhance motor neuron
      differentiation.
AB  - Derivation of motor neurons from human pluripotent stem cells is inefficient and
      requires complex culture protocols. Recently in Nature Materials, Sun et al.
      (2014) report that differentiating human pluripotent stem cells on soft
      substrates increases the efficiency of mature motor neuron differentiation by
      altering cytoskeletal mechanotransduction through the Hippo/YAP/Smad pathway.

PMID- 24905161
TI  - Saying no to drugs: fasting protects hematopoietic stem cells from chemotherapy
      and aging.
AB  - Aging and chemotherapeutics damage hematopoietic stem cells (HSCs), leading to
      dysregulation of asymmetric division and subsequent immunosuppression and blood
      related diseases. In this issue, Cheng et al. (2014) use prolonged fasting as a
      medical intervention to decrease IGF-1/PKA signaling and protect HSCs against
      chemotherapeutic toxicity and promote rejuvenation.

PMID- 24905162
TI  - Reprogramming the methylome: erasing memory and creating diversity.
AB  - The inheritance of epigenetic marks, in particular DNA methylation, provides a
      molecular memory that ensures faithful commitment to transcriptional programs
      during mammalian development. Epigenetic reprogramming results in global
      hypomethylation of the genome together with a profound loss of memory, which
      underlies naive pluripotency. Such global reprogramming occurs in primordial germ
      cells, early embryos, and embryonic stem cells where reciprocal molecular links
      connect the methylation machinery to pluripotency. Priming for differentiation is
      initiated upon exit from pluripotency, and we propose that epigenetic mechanisms
      create diversity of transcriptional states, which help with symmetry breaking
      during cell fate decisions and lineage commitment. 

PMID- 24905164
TI  - Chromatin repressive complexes in stem cells, development, and cancer.
AB  - The chromatin environment is essential for the correct specification and
      preservation of cell identity through modulation and maintenance of transcription
      patterns. Many chromatin regulators are required for development, stem cell
      maintenance, and differentiation. Here, we review the roles of the polycomb
      repressive complexes, PRC1 and PRC2, and the HDAC1- and HDAC2-containing
      complexes, NuRD, Sin3, and CoREST, in stem cells, development, and cancer, as
      well as the ongoing efforts to develop therapies targeting these complexes in
      human cancer. Furthermore, we discuss the role of repressive complexes in
      modulating thresholds for gene activation and their importance for specification
      and maintenance of cell fate. 

PMID- 24905163
TI  - Molecular control of induced pluripotency.
AB  - Deciphering the mechanisms of epigenetic reprogramming provides fundamental
      insights into cell fate decisions, which in turn reveal strategies to make the
      reprogramming process increasingly efficient. Here we review recent advances in
      epigenetic reprogramming to pluripotency with a focus on the principal molecular
      regulators. We examine the trajectories connecting somatic and pluripotent cells,
      genetic and chemical methodologies for inducing pluripotency, the role of
      endogenous master transcription factors in establishing the pluripotent state,
      and functional interactions between reprogramming factors and epigenetic
      regulators. Defining the crosstalk among the diverse molecular actors implicated
      in cellular reprogramming presents a major challenge for future inquiry. 

PMID- 24905165
TI  - Long noncoding RNAs in cell-fate programming and reprogramming.
AB  - In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class
      of regulators of gene expression. lncRNAs exhibit several distinctive features
      that confer unique regulatory functions, including exquisite cell- and tissue
      specific expression and the capacity to transduce higher-order spatial
      information. Here we review evidence showing that lncRNAs exert critical
      functions in adult tissue stem cells, including skin, brain, and muscle, as well
      as in developmental patterning and pluripotency. We highlight new approaches for
      ascribing lncRNA functions and discuss mammalian dosage compensation as a classic
      example of an lncRNA network coupled to stem cell differentiation. 

PMID- 24905166
TI  - The 3D genome in transcriptional regulation and pluripotency.
AB  - It can be convenient to think of the genome as simply a string of nucleotides,
      the linear order of which encodes an organism's genetic blueprint. However, the
      genome does not exist as a linear entity within cells where this blueprint is
      actually utilized. Inside the nucleus, the genome is organized in three
      dimensional (3D) space, and lineage-specific transcriptional programs that direct
      stem cell fate are implemented in this native 3D context. Here, we review
      principles of 3D genome organization in mammalian cells. We focus on the emerging
      relationship between genome organization and lineage-specific transcriptional
      regulation, which we argue are inextricably linked. 

PMID- 24905167
TI  - Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based
      regeneration and reverse immunosuppression.
AB  - Immune system defects are at the center of aging and a range of diseases. Here,
      we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity
      in various cell populations, leading to signal transduction changes in long-term
      hematopoietic stem cells (LT-HSCs) and niche cells that promote stress
      resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of
      fasting abated the immunosuppression and mortality caused by chemotherapy and
      reversed age-dependent myeloid-bias in mice, in agreement with preliminary data
      on the protection of lymphocytes from chemotoxicity in fasting patients. The
      proregenerative effects of fasting on stem cells were recapitulated by
      deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1. These
      findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and
      establish their crucial role in regulating hematopoietic stem cell protection,
      self-renewal, and regeneration. 

PMID- 24905168
TI  - Reorganization of enhancer patterns in transition from naive to primed
      pluripotency.
AB  - Naive and primed pluripotency is characterized by distinct signaling
      requirements, transcriptomes, and developmental properties, but both cellular
      states share key transcriptional regulators: Oct4, Sox2, and Nanog. Here, we
      demonstrate that transition between these two pluripotent states is associated
      with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer
      chromatin landscapes. Our genomic and biochemical analyses identified candidate
      mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even
      when differentiation cues are blocked, premature Otx2 overexpression is
      sufficient to exit the naive state, induce transcription of a substantial subset
      of primed pluripotency-associated genes, and redirect Oct4 to previously
      inaccessible enhancer sites. However, the ability of Otx2 to engage new enhancer
      regions is determined by its levels, cis-encoded properties of the sites, and the
      signaling environment. Our results illuminate regulatory mechanisms underlying
      pluripotency and suggest that the capacity of transcription factors such as Otx2
      and Oct4 to pioneer new enhancer sites is highly context dependent. 

PMID- 24905169
TI  - Epigenomic comparison reveals activation of "seed" enhancers during transition
      from naive to primed pluripotency.
AB  - Naive mouse embryonic stem cells (mESCs) and primed epiblast stem cells (mEpiSCs)
      represent successive snapshots of pluripotency during embryogenesis. Using
      transcriptomic and epigenomic mapping we show that a small fraction of
      transcripts are differentially expressed between mESCs and mEpiSCs and that these
      genes show expected changes in chromatin at their promoters and enhancers.
      Unexpectedly, the cis-regulatory circuitry of genes that are expressed at
      identical levels between these cell states also differs dramatically. In mESCs,
      these genes are associated with dominant proximal enhancers and dormant distal
      enhancers, which we term seed enhancers. In mEpiSCs, the naive-dominant enhancers
      are lost, and the seed enhancers take up primary transcriptional control. Seed
      enhancers have increased sequence conservation and show preferential usage in
      downstream somatic tissues, often expanding into super enhancers. We propose that
      seed enhancers ensure proper enhancer utilization and transcriptional fidelity as
      mammalian cells transition from naive pluripotency to a somatic regulatory
      program.

PMID- 24905170
TI  - Klf2 is an essential factor that sustains ground state pluripotency.
AB  - The maintenance of mouse embryonic stem cells (mESCs) requires LIF and serum.
      However, a pluripotent "ground state," bearing resemblance to preimplantation
      mouse epiblasts, can be established through dual inhibition (2i) of both
      prodifferentiation Mek/Erk and Gsk3/Tcf3 pathways. While Gsk3 inhibition has been
      attributed to the transcriptional derepression of Esrrb, the molecular mechanism
      mediated by Mek inhibition remains unclear. In this study, we show that Kruppel
      like factor 2 (Klf2) is phosphorylated by Erk2 and that phospho-Klf2 is
      proteosomally degraded. Mek inhibition hence prevents Klf2 protein
      phosphodegradation to sustain pluripotency. Indeed, while Klf2-null mESCs can
      survive under LIF/Serum, they are not viable under 2i, demonstrating that Klf2 is
      essential for ground state pluripotency. Importantly, we also show that ectopic
      Klf2 expression can replace Mek inhibition in mESCs, allowing the culture of Klf2
      null mESCs under Gsk3 inhibition alone. Collectively, our study defines the
      Mek/Erk/Klf2 axis that cooperates with the Gsk3/Tcf3/Esrrb pathway in mediating
      ground state pluripotency. 

PMID- 24905172
TI  - Understanding the switch from pain-to-itch in dermatitis.

PMID- 24905171
TI  - Does the age-related "anterior shift" of the P3 reflect an inability to habituate
      the novelty response?
AB  - Old adults often generate larger anterior neural responses than young adults when
      carrying out task requirements. A common finding in the ERP literature is an
      "anterior shift" of the P3b to targets. Utilizing principal component analysis
      (PCA), we recently demonstrated that rather than the P3b moving anteriorly, old
      adults generate a large P3a that temporally overlaps with their P3b. A dominant
      hypothesis for the age-related increase in anterior P3 is the failure to
      habituate the brain's novelty response to rare targets. We tested this hypothesis
      in young and old adults by comparing the amplitude of the PCA factor representing
      P3a to targets presented in the first versus last of eight blocks of a visual
      oddball task. If, unlike young adults, old adults are unable to habituate a
      novelty response, one would expect (1) the P3a amplitude to decrease between the
      first and last blocks for young, but not old subjects and (2) the difference in
      P3a amplitude between young and old subjects to be greater in the last than the
      first block. Our results indicate the amplitude of the P3a was larger in old
      adults than young adults. However, this effect was not modulated by block. These
      findings argue against the hypothesis that an age-related increase in the P3a to
      targets reflects an inability of old subjects to habituate a novelty response. An
      alternative hypothesis is that the augmented P3a indexes the increased
      utilization of frontal executive functions to provide compensatory scaffolding to
      carry out a task. 

PMID- 24905173
TI  - Does chloride channel accessory 3 have a role in arthritis pain? A study on
      murine antigen-induced arthritis.
AB  - Calcium-activated chloride channels (CaCCs) are thought to regulate neuronal
      excitability, and recently chloride (Cl(-)) regulation in DRG neurons has
      attracted much attention in pain research. Furthermore, the activity of CaCCs is
      modified by a family of CLCA proteins. In acute antigen-induced arthritis (AIA),
      a remarkable up-regulation of the murine chloride channel accessory 3 (mClca3)
      was shown in dorsal root ganglion (DRG) neurons. Therefore we tested the
      hypothesis that mClca3 is involved in arthritic pain perception. In mClca3 knock
      out mice and wild-type control mice, AIA was induced and measures of inflammation
      and pain were assessed. In the very acute phase of AIA, joint swelling was
      reduced in mClca3 knock-out mice. This effect disappeared during the course of
      AIA. We could not show significant differences in mechanical hyperalgesia between
      both groups of mice, neither at the acute nor at the chronic stage (21 days of
      AIA). Additional experiments on thermal hyperalgesia in wild-type and mClca3
      knock-out mice in the first 3 days of AIA did not show a difference either. In
      addition, niflumic acid, an antagonist at CaCCs, did not significantly influence
      hyperalgesia during AIA. Thus, we were not able to provide evidence for a role of
      CaCCs, and in particular of mClca3, on the expression of arthritis or
      inflammation-evoked hyperalgesia. 

PMID- 24905174
TI  - Acupuncture at HT7 suppresses morphine self-administration at high dose through
      GABA system.
AB  - In the previous study, acupuncture at HT7 has shown to attenuate the self
      administration of morphine at a low dose (0.1mg/kg). In this study, it was
      further investigated whether acupuncture at HT7 could attenuate the morphine self
      administration at a high dose (0.5mg/kg). Male Sprague-Dawley rats weighing 270
      300g were used. After surgery of catheterization, animals were trained to self
      administer morphine solution (0.5mg/kg) using daily 1h session under fixed ratio
      1 schedule for 3 weeks. Animals that had shown stable morphine-taking (establish
      baseline: variation less than 20% of the mean of three consecutive days) were
      subjected to the acupuncture treatment. Bicuculline and SCH 50911 were used to
      investigate the possible relation between the effect of acupuncture and the GABA
      receptor system. Acupuncture at HT7, but not at control acupoint, LI5, suppressed
      spontaneous morphine-taking behavior significantly. In addition, the effect of
      acupuncture was blocked by both GABA receptor antagonists. The results of this
      study suggest that acupuncture at HT7 suppresses morphine-taking behavior through
      the mediation of GABA receptor system. 

PMID- 24905175
TI  - Fasudil reduces GFAP expression after hypoxic injury.
AB  - Fasudil (HA-1077), a specific Rho kinase II (ROCKII) inhibitor, is in clinical
      trials for recovery from spinal cord injury (SCI). The primary role of Fasudil is
      in axonal regeneration, as it inhibits ROCKII, the key signaling molecule
      involved in collapse of axon growth cone. Astrogliosis, due to the activation of
      astrocytes is an indicator of CNS injury. In early stages of injury, GFAP
      expression increases, helping to restore the integrity of the CNS. An increase in
      GFAP expression is also a marker of astrogliosis. Thus, reducing GFAP and hence
      astrogliosis at later stages of SCI is important for neuroregeneration and
      functional recovery. CoCl2 was used to induce hypoxic injury in astrocytic cell
      lines A172 (24h) and in spinal cord dorsal column white matter (8h). Several
      different techniques were used to study the changes in GFAP expression such as
      real-time PCR, western blotting and immunofluorescence staining with confocal
      microscopy. Hypoxia increased the expression of GFAP in A172 cells and in the
      spinal cord dorsal column after CoCl2 (100MUM) treatment for 24h and 8h,
      respectively. We observed 11 folds increase in protein expression in A172 cells
      (24h) and 4.5 folds in spinal cord dorsal column (8h). The RNA expression was
      increased 3 folds in A172 cells after 24h of treatment and 4 folds in spinal cord
      dorsal column after 8h of treatment with 100MUM CoCl2. Treatment with fasudil
      (20MUM) significantly reduces the expression of GFAP in A172 cells and in spinal
      cord dorsal column. Fasudil also decreased activation of NF-kappaB in A172 cells
      after hypoxic injury. In the present study, we observed that fasudil reduces the
      expression of GFAP (consequently, astrogliosis) after hypoxic injury to A172
      cells and spinal cord dorsal column. Our studies demonstrate that fasudil also
      plays a role in GFAP expression by reducing NF-kappaB activation at the injury
      site which could further help in axonal regeneration. 

PMID- 24905176
TI  - Modifying a known gelator scaffold for nitrite detection.
AB  - The process of selecting and modifying a known gelator scaffold to develop a new
      nitrite-based sensor is described. Five new azo-sulfonate gelators were
      discovered and characterized. The most promising scaffold exhibits a stable
      diazonium intermediate, proceeds in a high yield, and gels nitrite-spiked tap,
      river, and pond water. 

PMID- 24905177
TI  - Superior mechanical performance of highly porous, anisotropic nanocellulose
      montmorillonite aerogels prepared by freeze casting.
AB  - Directionally solidified nanofibrillated cellulose (NFC)-sodium-montmorillonite
      (MMT) composite aerogels with a honeycomb-like pore structure were compared with
      non-directionally frozen aerogels with equiaxed pore structure and identical
      composition and found to have superior functionalities. To explore structure
      property correlations, three different aerogel compositions of 3wt% MMT, and
      0.4wt%, 0.8wt%, and 1.2wt% NFC, respectively, were tested. Young's modulus,
      compressive strength and toughness were found to increase with increasing NFC
      content for both architectures. The modulus increased from 25.8kPa to 386kPa for
      the isotropic and from 2.13MPa to 3.86MPa for the anisotropic aerogels, the
      compressive yield strength increased from 3.3kPa to 18.0kPa for the isotropic and
      from 32.3kPa to 52.5kPa for the anisotropic aerogels, and the toughness increased
      from 6.3kJ/m(3) to 24.1kJ/m(3) for the isotropic and from 22.9kJ/m(3) to
      46.2kJ/m(3) for the anisotropic aerogels. The great range of properties, which
      can be achieved through compositional as well as architectural variations, makes
      these aerogels highly attractive for a large range of applications, for which
      either a specific composition, or a particular pore morphology, or both are
      required. Finally, because NFC is flammable, gasification experiments were
      performed, which revealed that the inclusion of MMT increased the heat endurance
      and shape retention functions of the aerogels dramatically up to 800 degrees C
      while the mechanical properties were retained up to 300 degrees C. 

PMID- 24905178
TI  - Strengthening of dental adhesives via particle reinforcement.
AB  - The bond between methacrylic polymer adhesives and dental restoratives is not
      perfect and may fail either in the short or in the long term. This study aims to
      evaluate the effects of particle incorporation in a self-etch model adhesive on
      mechanical and physical properties that are relevant during application and
      service. Filled adhesives containing 5, 10, 15 or 25wt% glass fillers were
      compared to their unfilled counterpart in terms of water sorption and solubility;
      viscosity and dynamic viscosity during polymerization were recorded using
      rheological measurements and compared to FTIR analysis of the real-time degree of
      cure. Elastic modulus and ultimate tensile strength measurements were performed
      in uniaxial tension; the energy to fracture was used to calculate the fracture
      toughness of the adhesives. Finally, the experimental adhesives were applied on
      dentin substrate to test the bond strength using the microtensile test. Results
      showed that the incorporation of 5-10wt% nanofiller to self-etching dental
      adhesives is efficient in accelerating the polymerization reaction and increasing
      the degree of cure without compromising the film viscosity for good wettability
      or water sorption and solubility. Fillers increased the elastic modulus, tensile
      strength and fracture toughness to a plateau between 5 and 15wt% filler
      concentration, and despite the tendency to form agglomerations, active crack
      pinning/deflection toughening mechanisms have been observed. The bond strength
      between resin composite and dentin was also improved when adhesives with up to
      10wt% fillers were used, with no additional improvements with further packing.
      The use of fillers to reinforce dental adhesives may therefore be of great
      practical benefit by improving curing and mechanical properties. 

PMID- 24905179
TI  - Characterization and nanomechanical properties of novel dental implant coatings
      containing copper decorated-carbon nanotubes.
AB  - Fluorapatite-titania coated Ti-based implants are promising for using in dental
      surgery for restoring teeth. One of the challenges in implantology is to achieve
      a bioactive coating with appropriate mechanical properties. In this research,
      simple sol-gel method was developed for synthesis of fluorapatite-titania-carbon
      nanotube decorated with antibacterial agent. Triethyl phosphate [PO4(C2H5)3],
      calcium nitrate [Ca(NO3)2] and ammonium fluoride (NH4F) were used as precursors
      under an ethanol-water based solution for fluorapatite (FA) production. Titanium
      isopropoxide and isopropanol were used as starting materials for making TiO2 sol
      gels. Also, Copper acetate [Cu(C2H3O2)2.H2O] was used as precursor for decoration
      of multi walled carbon nanotubes (MWCNTs) with wet chemical method. The decorated
      MWCNTs (CNT(Cu)) were evaluated by transmission electron microscopy (TEM). The
      phase identification of the FA-TiO2-CNT(Cu) coating was carried out by XRD
      analysis. Morphology of coated samples was investigated by SEM observations. The
      surface elastic modulus and hardness of coatings were studied using
      nanoindentation technique. The results indicate that novel dental implant coating
      containing FA, TiO2 and copper decorated MWCNTs have proper morphological
      features. The results of nanoindentation test show that incorporation of CNT(Cu)
      in FA-TiO2 matrix can improve the nanomechanical properties of composite coating.

PMID- 24905180
TI  - Effect of grinding with diamond-disc and -bur on the mechanical behavior of a Y
      TZP ceramic.
AB  - This study compared the effects of grinding on the surface micromorphology, phase
      transformation (t->m), biaxial flexural strength and structural reliability
      (Weibull analysis) of a Y-TZP (Lava) ceramic using diamond-discs and -burs. 170
      discs (15*1.2mm) were produced and divided into 5 groups: without treatment
      (Ctrl, as-sintered), and ground with 4 different systems: extra-fine (25um,
      Xfine) and coarse diamond-bur (181um, Coarse), 600-grit (25um, D600) and 120-grit
      diamond-disc (160um, D120). Grinding with burs was performed using a contra-angle
      handpiece (T2-Revo R170, Sirona), while for discs (Allied) a Polishing Machine
      (Ecomet, Buehler) was employed, both under water-cooling. Micromorphological
      analysis showed distinct patterns generated by grinding with discs and burs,
      independent of grit size. There was no statistical difference for characteristic
      strength values (MPa) between smaller grit sizes (D600 - 1050.08 and Xfine -
      1171.33), although they presented higher values compared to Ctrl (917.58). For
      bigger grit sizes, a significant difference was observed (Coarse - 1136.32>D120 -
      727.47). Weibull Modules were statistically similar between the tested groups.
      Within the limits of this study, from a micromorphological point-of-view, the
      treatments performed did not generate similar effects, so from a methodological
      point-of-view, diamond-discs should not be employed to simulate clinical abrasion
      performed with diamond-burs on Y-TZP ceramics. 

PMID- 24905182
TI  - Stenting of the obstructed ductus venosus as emergency and bridging strategy in a
      very low birth weight infant with infradiaphragmatic total anomalous pulmonary
      venous connection.
AB  - A very low birth weight neonate (1.2 kg) with total anomalous pulmonary venous
      connection and obstructed infracardiac pulmonary venous drainage was treated by
      stenting of the ductus venosus via a transjugular approach. With one
      reintervention to dilate an in-stent stenosis, the palliative stented situation
      stabilized the patient for as long as three months until definitive surgical
      correction at a weight of 2 kg. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24905181
TI  - African American women's perceptions of cancer clinical trials.
AB  - Cancer clinical trials are important for resolving cancer health disparities for
      several reasons; however, clinical trial participation among African Americans is
      significantly lower than Caucasians. This study engaged focus groups of 82 female
      African American cancer survivors or cancer caregivers, including those in better
      resourced, more urban areas and less resourced, more rural areas. Informed by an
      integrated conceptual model, the focus groups examined perceptions of cancer
      clinical trials and identified leverage points that future interventions may use
      to improve enrollment rates. Study findings highlight variation in community
      knowledge regarding cancer clinical trials, and the importance of community
      education regarding clinical trials and overcoming historical stigma associated
      with clinical research specifically and the health care system more generally.
      Study participants commented on the centrality of churches in their communities,
      and thus the promise of the church as loci of such education. Findings also
      suggested the value of informed community leaders as community information
      sources, including community members who have a previous diagnosis of cancer and
      clinical trial experience. The sample size and location of the focus groups may
      limit the generalizability of the results. Since the women in the focus groups
      were either cancer survivors or caregivers, they may have different experiences
      than nonparticipants who lack the close connection with cancer. Trust in the
      health system and in one's physician was seen as important factors associated
      with patient willingness to enroll in clinical trials, and participants suggested
      that physicians who were compassionate and who engaged and educated their
      patients would build important trust requisite for patient participation in
      clinical trials. 

PMID- 24905183
TI  - Expression of survivin and p53 modulates honokiol-induced apoptosis in colorectal
      cancer cells.
AB  - Honokiol is a small biphenolic compound, which exerts antitumor activities;
      however, the precise mechanism of honokiol-induced apoptosis in the human
      colorectal cancer cells remains unclear. Here, we show that survivin and p53
      display the opposite role on the regulation of honokiol-induced apoptosis in the
      human colorectal cancer cells. Honokiol induced the cell death and apoptosis in
      various colorectal cancer cell lines. Moreover, honokiol elicited the extrinsic
      death receptor pathway of DR5 and caspase 8 and the intrinsic pathway of caspase
      9. The common intrinsic and extrinsic downstream targets of activated caspase 3
      and PARP protein cleavage were induced by honokiol. Interestingly, honokiol
      reduced anti-apoptotic survivin protein and gene expression. Transfection with a
      green fluorescent protein (GFP)-survivin-expressed vector increased the
      colorectal cancer cell viability and resisted the honokiol-induced apoptosis.
      Meantime, honokiol increased total p53 and the phosphorylated p53 proteins at
      Ser15 and Ser46. The p53-wild type colorectal cancer cells were exhibited greater
      cytotoxicity, apoptosis and survivin reduction than the p53-null cancer cells
      after treatment with honokiol. Together, these findings demonstrate that the
      existence of survivin and p53 can modulate the honokiol-induced apoptosis in the
      human colorectal cancer cells.

PMID- 24905184
TI  - Metal ions and solvents ratio co-regulate four new magnetic coordination polymers
      based upon an unsymmetric tricarboxylate acid ligand.
AB  - Four new coordination polymers (CPs), [Co3(L)2(bib)3(EtOH)2].2H2O (1),
      [Mn3(L)2(bib)2(H2O)4].4H2O (2), [Ni(HL)(bib)(H2O)3] (3) and
      [Ni3(bib)4(H2O)10].2(L).12(H2O) (4), were synthesized under solvothermal
      conditions with an unsymmetrical tricarboxylic acid ligand [biphenyl-3,3',5
      tricarboxylic acid (H3L)] in the presence of the 1,4-bis(1H-imidazol-4-yl)benzene
      (bib) ligand. In compound 1, tricarboxylate acid ligands (H3L) link Co centers to
      generate two-dimensional (2D) layers which are further connected by bib ligands
      to exhibit a three-dimensional (3D) framework with a (4,4,5)-connected
      (4(2).6(3).8)2(4(2).6(7).8)2(6(4).8.10) topology. The three-dimensional (3D)
      framework of 2 is defined as a (3,3,4)-connected topology with the point symbol
      of (6.8(2))2(6(2).8)2(8.10(4).12). Compound 3 contains a one-dimensional (1D)
      left-hand helix chain along the a direction and further extends into a 2D
      supramolecular network and a 3D supramolecular framework via hydrogen bonds.
      Compound 4 displays a one-dimensional (1D) molecular ladder, which is further
      combined with each other through pi...pi stacking to extend into 2D
      supramolecular sheets. The supramolecular networks of 3 and 4 resulted from the
      different solvent ratios [V(H2O)-V(EtOH)] in the reaction. All the CPs are
      characterized by single-crystal X-ray diffraction analyses, powder X-ray
      diffraction (PXRD), elemental analyses, IR spectroscopy, and TGA analyses.
      Moreover, the weak ferromagnetic properties of 2 and 3 and antiferromagnetic
      properties of 1 and 4 have also been investigated.

PMID- 24905185
TI  - Endolymphatic sac surgical anatomy and transmastoid decompression of the sac for
      the management of Meniere's disease.
AB  - BACKGROUND: Decompression of the endolymphatic sac for Meniere's disease gives
      unpredictable results. This may be because the sac is difficult to identify and
      decompress accurately without causing surgical trauma. METHODS: In order to test
      this idea, transmastoid decompression was simulated in 5 cadaver half heads and
      the anatomy of the endolymphatic sac was reviewed in a further 14 specimens.
      RESULTS: The endolymphatic sac was found and confirmed by histology in all five
      simulated decompressions. A newly described feature, a trapezoid thickening of
      dura, was a useful guide. The review showed that the sac was constant proximally,
      but variable distally. The posterior semicircular canal, posterior fossa dura and
      sigmoid sinus are at risk during dissection. CONCLUSION: The endolymphatic sac
      may be identified on inspection by an overlying patch of dura, thereby reducing
      exploratory dissection. It is best to decompress the sac as far proximally as
      possible, whilst protecting the posterior semicircular canal.

PMID- 24905186
TI  - Ten-year trends in total physical activity practice in Brazilian adults: 2002
      2012.
AB  - BACKGROUND: One-third of adults worldwide are physically inactive causing over
      5.3 million deaths annually. Despite a growing focus on physical activity and
      health, population-based data on physical activity trends in low- and middle
      income countries are still limited. To help fill the gap, this study provides
      trend data over a 10-year period in Pelotas, a southern Brazilian city. METHODS:
      The short version of the International Physical Activity Questionnaire was used
      to assess the prevalence of physical inactivity in 2002 (n = 3119), 2007 (n =
      2969), and 2012 (n = 2868). Levels of inactivity and trends were assessed
      according to sex, age, schooling, and socioeconomic position (SEP). RESULTS: The
      prevalence of physical inactivity rose from 41.1% (95% CI: 37.4-44.9) in 2002 and
      52.0% (95% CI: 49.1-53.8) in 2007 to 54.4% (95% CI: 51.8-56.9) in 2012 (P <
      .001). Physical inactivity significantly increased in all subgroups except in the
      highest SEP and 70+ year age subgroups. CONCLUSIONS: After a sharp increase in
      the prevalence of physical inactivity from 2002-2007, levels plateaued from 2007
      2012. However, it is important to stress that current levels are still
      unacceptably high, and that efforts must be intensified to reverse the trend.

PMID- 24905187
TI  - Measuring and Statistically Testing the Size of the Effect of a Chemical Compound
      on a Continuous In-Vitro Pharmacological Response Through a New Statistical Model
      of Response Detection Limit.
AB  - Biomolecular screening research frequently searches for the chemical compounds
      that are most likely to make a biochemical or cell-based assay system produce a
      strong continuous response. Several doses are tested with each compound and it is
      assumed that, if there is a dose-response relationship, the relationship follows
      a monotonic curve, usually a version of the median-effect equation. However, the
      null hypothesis of no relationship cannot be statistically tested using this
      equation. We used a linearized version of this equation to define a measure of
      pharmacological effect size, and use this measure to rank the investigated
      compounds in order of their overall capability to produce strong responses. The
      null hypothesis that none of the examined doses of a particular compound produced
      a strong response can be tested with this approach. The proposed approach is
      based on a new statistical model of the important concept of response detection
      limit, a concept that is usually neglected in the analysis of dose-response data
      with continuous responses. The methodology is illustrated with data from a study
      searching for compounds that neutralize the infection by a human immunodeficiency
      virus of brain glioblastoma cells. 

PMID- 24905189
TI  - Drug-drug interaction between NSAIDS and low-dose aspirin: a focus on
      cardiovascular and GI toxicity.
AB  - INTRODUCTION: The aging of the population in the US and other countries means
      that a large number of people will likely take NSAIDs for the relief of pain and
      low-dose aspirin (LD-ASA) for cardioprotection. However, the cardioprotective
      value of LD-ASA can be compromised in patients who take NSAIDs concomitantly,
      because some NSAIDs competitively bind to critical amino-acid residues on
      cyclooxygenase (COX) enzymes and interfere with the mechanism of antiplatelet
      activity of LD-ASA. AREAS COVERED: A review of the literature was conducted to
      provide an overview of current issues surrounding the concomitant use of NSAIDs
      and LD-ASA, to explore potential mechanisms for this drug-drug interaction and to
      consider current and future treatment options that may mitigate the risk
      associated with their concomitant use. EXPERT OPINION: NSAIDs offer effective
      pain relief for the most common forms of pain, such as low back pain,
      musculoskeletal pain associated with arthritis, postsurgical pain, headache,
      acute pain syndromes, menstrual pain and dental pain. The development of NSAID
      formulations that offer effective pain control with fewer or less serious adverse
      effects due to interference with ASA would be a valuable medical advance. Several
      promising treatment options and regimens may be available in the future.

PMID- 24905190
TI  - Transit-Related Walking to Work in Promoting Physical Activity.
AB  - BACKGROUND: Transit-related walking to work is a potential strategy for
      incorporating physical activity into daily life and promoting health benefits.
      This study estimated the transit-related walking time for work trips on the
      journey to and from work and examined the predictors of transit users who walked
      to/from transit and the workplace and those who walked 30 minutes or more per
      day. METHODS: This study used the 2009 National Household Travel Survey and
      identified 772 subjects who took transit to/from work, 355 subjects who walked
      to/from transit and the workplace, and 145 subjects who walked 30 minutes or more
      per day among the 40,659 workers. Weighted logistic regressions were used for the
      analysis. RESULTS: Of the people who walked to/from transit and the workplace,
      40.9% walked 30 minutes or more per day. The weighted logistic regressions
      revealed that low-income groups and workers living in high population density
      areas were more likely to walk to/from transit and the workplace. Workers living
      in high population density areas were more likely to walk 30 minutes or more per
      day. CONCLUSIONS: Transit-related walking to work provides an opportunity to
      increase physical activity levels and to meet the physical activity
      recommendations.

PMID- 24905188
TI  - Dysregulation of Mfn2 and Drp-1 proteins in heart failure.
AB  - Therapeutic approaches for cardiac regenerative mechanisms have been explored
      over the past decade to target various cardiovascular diseases (CVD). Structural
      and functional aberrations of mitochondria have been observed in CVD. The
      significance of mitochondrial maturation and function in cardiomyocytes is
      distinguished by their attribution to embryonic stem cell differentiation into
      adult cardiomyocytes. An abnormal fission process has been implicated in heart
      failure, and treatment with mitochondrial division inhibitor 1 (Mdivi-1), a
      specific inhibitor of dynamin related protein-1 (Drp-1), has been shown to
      improve cardiac function. We recently observed that the ratio of mitofusin 2
      (Mfn2; a fusion protein) and Drp-1 (a fission protein) was decreased during heart
      failure, suggesting increased mitophagy. Treatment with Mdivi-1 improved cardiac
      function by normalizing this ratio. Aberrant mitophagy and enhanced oxidative
      stress in the mitochondria contribute to abnormal activation of MMP-9, leading to
      degradation of the important gap junction protein connexin-43 (Cx-43) in the
      ventricular myocardium. Reduced Cx-43 levels were associated with increased
      fibrosis and ventricular dysfunction in heart failure. Treatment with Mdivi-1
      restored MMP-9 and Cx-43 expression towards normal. In this review, we discuss
      mitochondrial dynamics, its relation to MMP-9 and Cx-43, and the therapeutic role
      of fission inhibition in heart failure. 

PMID- 24905191
TI  - Evidence of natural Wolbachia infections in field populations of Anopheles
      gambiae.
AB  - Wolbachia are maternally transmitted intracellular bacteria that invade insect
      populations by manipulating their reproduction and immunity and thus limiting the
      spread of numerous human pathogens. Experimental Wolbachia infections can reduce
      Plasmodium numbers in Anopheles mosquitoes in the laboratory, however, natural
      Wolbachia infections in field anophelines have never been reported. Here we show
      evidence of Wolbachia infections in Anopheles gambiae in Burkina Faso, West
      Africa. Sequencing of the 16S rRNA gene identified Wolbachia sequences in both
      female and male germlines across two seasons, and determined that these sequences
      are vertically transmitted from mother to offspring. Whole-genome sequencing of
      positive samples suggests that the genetic material identified in An. gambiae
      belongs to a novel Wolbachia strain, related to but distinct from strains
      infecting other arthropods. The evidence of Wolbachia infections in natural
      Anopheles populations promotes further investigations on the possible use of
      natural Wolbachia-Anopheles associations to limit malaria transmission. 

PMID- 24905192
TI  - Utilizing a Meals on Wheels program to teach falls risk assessment to medical
      students.
AB  - Falls are a critical public health issue for older adults, and falls risk
      assessment is an expected competency for medical students. The aim of this study
      was to design an innovative method to teach falls risk assessment using community
      based resources and limited geriatrics faculty. The authors developed a Fall
      Prevention Program through a partnership with Meals-on-Wheels (MOW). A 3rd-year
      medical student accompanies a MOW client services associate to a client's home
      and performs a falls risk assessment including history of falls, fear of falling,
      medication review, visual acuity, a Get Up and Go test, a Mini-Cog, and a home
      safety evaluation, reviewed in a small group session with a faculty member.
      During the 2010 academic year, 110 students completed the in-home falls risk
      assessment, rating it highly. One year later, 63 students voluntarily completed a
      retrospective pre/postsurvey, and the proportion of students reporting moderate
      to very high confidence in performing falls risk assessments increased from 30.6%
      to 87.3% (p < .001). Students also reported using most of the skills learned in
      subsequent clerkships. A single educational intervention in the MOW program
      effectively addressed geriatrics competencies with minimal faculty effort and
      could be adopted by many medical schools. 

PMID- 24905193
TI  - A pattern-mixture model with nonfuture dependence and shift in current missing
      values.
AB  - For incomplete continuous longitudinal data with a monotone pattern, we study a
      pattern-mixture model which assumes that missingness only depends on observed
      data and the current missing value, and that the conditional distribution of the
      current missing value differ from that of the observed patterns by location and
      scale shifts. The shift parameters measure the departure from the missing at
      random mechanism. We show that a numerical or Monte Carlo approximation is needed
      to obtain the posterior draw of the mean at the final time point as a function of
      the posterior draw of the observed data model parameters and shift parameters,
      and that scale shifts have negligible impact on the estimated mean at the final
      time point. We use multiple imputation to avoid numerical integration and
      demonstrate that the usual multiple imputation variance estimator is valid for
      the estimated mean at the final time point when scale shifts are not considered.
      The multiple imputation method is applied to a clinical study of major depressive
      disorders. 

PMID- 24905194
TI  - Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the
      heart from ischemia and reperfusion.
AB  - Nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme for
      nicotinamide adenine dinucleotide (NAD+) synthesis, and Sirt1, an NAD+-dependent
      histone deacetylase, protect the heart against ischemia/reperfusion (I/R). It
      remains unknown whether Nampt mediates the protective effect of ischemic
      preconditioning (IPC), whether nicotinamide mononucleotide (NMN, 500 mg/kg), a
      product of Nampt in the NAD+ salvage pathway, mimics the effect of IPC, or
      whether caloric restriction (CR) upregulates Nampt and protects the heart through
      a Sirt1-dependent mechanism. IPC upregulated Nampt protein, and the protective
      effect of IPC against ischemia (30 minutes) and reperfusion (24 hours) was
      attenuated at both early and late phases in Nampt +/- mice, suggesting that Nampt
      plays an essential role in mediating the protective effect of IPC. In order to
      mimic the effect of Nampt, NMN was administered by intraperitoneal injection. NMN
      significantly increased the level of NAD+ in the heart at baseline and prevented
      a decrease in NAD+ during ischemia. NMN protected the heart from I/R injury when
      it was applied once 30 minutes before ischemia or 4 times just before and during
      reperfusion, suggesting that exogenous NMN protects the heart from I/R injury in
      both ischemic and reperfusion phases. The protective effect of NMN was
      accompanied by decreases in acetylation of FoxO1, but it was not obvious in Sirt1
      KO mice, suggesting that the effect of NMN is mediated through activation of
      Sirt1. Compared to control diet (90% calories), CR (60% calories for 6 weeks) in
      mice led to a significant reduction in I/R injury, accompanied by upregulation of
      Nampt. The protective effect of CR against I/R injury was not significant in
      cardiac-specific Sirt1 KO mice, suggesting that the protective effect of CR is in
      part mediated through the Nampt-Sirt1 pathway. In conclusion, exogenous
      application of NMN and CR protects the heart by both mimicking IPC and activating
      Sirt1. 

PMID- 24905196
TI  - Biological functions of double-stranded RNA and its binding proteins.

PMID- 24905197
TI  - Philip I. Marcus: a gentleman of science (1927-2013).

PMID- 24905195
TI  - The form of a conditioned stimulus can influence the degree to which it acquires
      incentive motivational properties.
AB  - There is considerable individual variation in the extent to which food- and drug
      associated cues (conditioned stimuli, CSs) acquire incentive salience, as
      indicated by whether they elicit approach towards them, and/or act as conditioned
      reinforcers. Here we asked whether this variation is influenced by properties of
      the CS itself. In rats, we assessed both the attractiveness and conditioned
      reinforcing properties of two CSs: a manipulable lever CS versus an auditory
      (tone) CS. There was considerable individual variation in the extent to which a
      lever CS acquired incentive motivational properties, as indicated by whether it
      became attractive (evoked a sign-tracking or goal-tracking conditioned response)
      or acted as a conditioned reinforcer. However, with a tone CS all rats learned a
      goal-tracking response, and the tone CS was an equally effective conditioned
      reinforcer in sign-trackers and goal-trackers. Even when presented in compound (a
      lever-tone CS), the two elements of the compound differentially acquired
      motivational properties. In contrast, amphetamine and stress potentiated the
      conditioned reinforcing properties of both visual and auditory CSs similarly in
      rats that primarily sign-tracked or goal-tracked. We conclude that variation in
      the to the ability of CSs to acquire incentive salience, and thus their ability
      to act as incentive stimuli capable of motivating behavior, is determined in part
      by properties of the CS itself. 

PMID- 24905198
TI  - Extracellular dsRNA: its function and mechanism of cellular uptake.
AB  - Double-stranded RNA (dsRNA) is arguably the most potent viral trigger of innate
      immune signaling. Its activity has been recognized for over 5 decades, first as a
      toxin, then as a central component of the interferon system, as an efficient
      activator of antiviral responses and an immunomodulator for therapeutic
      applications. Nucleic acid sensing is the main basis for antiviral defense
      systems throughout the diverse forms of life from bacteria to plants and animals.
      Pattern recognition receptors of the host defense system not only sense viral
      dsRNA as a pathogen-associated molecular pattern in infected cells, but also
      recognize circulating endogenous dsRNA, a nonmicrobial signal, as a danger
      associated molecular pattern, often leading to autoimmunity. Despite the effects
      of extracellular viral and host dsRNA associated with infection and autoimmunity,
      respectively, the understanding of cellular mechanisms for its recognition and
      uptake has only been appreciated in recent years. This review presents an
      overview of this unique form of nucleic acid, addressing its roles in infection,
      autoimmunity, and host sensing mechanisms. The goal of this review is to
      highlight the novel findings with a focus on extracellular recognition and uptake
      by the cell. 

PMID- 24905199
TI  - dsRNA-activation of TLR3 and RLR signaling: gene induction-dependent and
      independent effects.
AB  - Double-stranded (ds) RNA has diverse roles in host defense and disease
      prevention. dsRNA, produced by viral replication, elicits strong antiviral
      responses in host; similar protective responses can also be triggered by cellular
      dsRNA produced by necrotic, apoptotic, or otherwise stressed, uninfected cells.
      dsRNA is recognized in the cell by a large family of dsRNA-binding proteins,
      among which are the pattern recognition receptors (PRRs), toll-like receptor 3
      (TLR3), and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). TLR3
      signals from the endosomal membrane where it senses extracellular dsRNA that has
      been endocytosed, whereas RLRs signal from the cytoplasm using a mitochondrial
      adaptor protein. In this review, we will summarize the signaling pathways used by
      these 2 PRRs, which lead to the activation of specific transcription factors and
      the induction of many proinflammatory and antiviral genes. However, it is
      becoming increasingly clear that all host responses are not mediated by the
      products of these induced genes; signal-dependent post-translational
      modifications of existing proteins can also profoundly change cellular
      properties. We will discuss how Src activation by TLR3 changes cell migration,
      adhesion, and proliferation rates and how IRF-3 activation by RLR triggers a gene
      induction-independent pro-apoptotic pathway that provides strong antiviral
      protection. 

PMID- 24905201
TI  - Protein kinase R and the inflammasome.
AB  - Protein kinase R (PKR) was first identified as a mediator of the double-stranded
      RNA (dsRNA)-mediated inhibition of protein synthesis in extracts from interferon
      treated cells. In a physiological context, viral replication results in
      production of dsRNA, activation of PKR by autophosphorylation, and
      phosphorylation of the protein synthesis initiation factor eIF2alpha. Subsequent
      biochemical, structural, and genetic analyses have identified the dsRNA and
      kinase domain structure of PKR, and shown that its deletion from the germline of
      mice results in impaired resistance to infection by many different viruses. These
      studies have also opened up roles for PKR in different signaling pathways, the
      most recent being regulation of the inflammasome. Here we review evidence for
      this newly ascribed function for PKR and discuss roles in inflammasome regulation
      and associated diseases. 

PMID- 24905200
TI  - An RNA editor, adenosine deaminase acting on double-stranded RNA (ADAR1).
AB  - Adenosine deaminase acting on RNA1 (ADAR1) catalyzes the C6 deamination of
      adenosine (A) to produce inosine (I) in regions of RNA with double-stranded (ds)
      character. This process is known as A-to-I RNA editing. Alternative promoters
      drive the expression of the Adar1 gene and alternative splicing gives rise to
      transcripts that encode 2 ADAR1 protein size isoforms. ADAR1 p150 is an
      interferon (IFN)-inducible dsRNA adenosine deaminase found in the cytoplasm and
      nucleus, whereas ADAR1 p110 is constitutively expressed and nuclear in
      localization. Dependent on the duplex structure of the dsRNA substrate,
      deamination of adenosine by ADAR can be either highly site-selective or
      nonspecific. A-to-I editing can alter the stability of RNA structures and the
      coding of RNA as I is read as G instead of A by ribosomes during mRNA translation
      and by polymerases during RNA replication. A-to-I editing is of broad physiologic
      significance. Both the production and the action of IFNs, and hence the
      subsequent interaction of viruses with their hosts, are among the processes
      affected by A-to-I editing. 

PMID- 24905203
TI  - Viral proteins that bind double-stranded RNA: countermeasures against host
      antiviral responses.
AB  - Several animal viruses encode proteins that bind double-stranded RNA (dsRNA) to
      counteract host dsRNA-dependent antiviral responses. This article discusses the
      structure and function of the dsRNA-binding proteins of influenza A virus and
      Ebola viruses (EBOVs). 

PMID- 24905204
TI  - Processing of double-stranded RNA in mammalian cells: a direct antiviral role?
AB  - Processing of viral double-stranded RNA (dsRNA) into small interfering RNAs
      (siRNAs) contributes directly to an antiviral effect in plants and invertebrates,
      which is amplified through the recruitment of RNA interference (RNAi). In
      mammals, viral dsRNAs are the substrate of the innate immune response and limit
      viral spread by impacting on cellular translation and cytokine production, as
      well as promoting cell death. Recent studies suggest that viral siRNAs also exert
      a direct antiviral activity in mammalian cells. Here, I review the current
      knowledge of dsRNA processing in mammalian cells and discuss the recent findings
      in light of the complex interplay between RNAi and dsRNA-driven innate immune
      responses toward the common goal of virus restriction. 

PMID- 24905202
TI  - Viral phosphodiesterases that antagonize double-stranded RNA signaling to RNase L
      by degrading 2-5A.
AB  - The host interferon (IFN) antiviral response involves a myriad of diverse
      biochemical pathways that disrupt virus replication cycles at many different
      levels. As a result, viruses have acquired and evolved genes that antagonize the
      host antiviral proteins. IFNs inhibit viral infections in part through the 2',5'
      oligoadenylate (2-5A) synthetase (OAS)/RNase L pathway. OAS proteins are pathogen
      recognition receptors that exist at different basal levels in different cell
      types and that are IFN inducible. Upon activation by the pathogen-associated
      molecular pattern viral double-stranded RNA, certain OAS proteins synthesize 2-5A
      from ATP. 2-5A binds to the antiviral enzyme RNase L causing its dimerization and
      activation. Recently, disparate RNA viruses, group 2a betacoronaviruses, and
      group A rotaviruses, have been shown to produce proteins with 2',5'
      phosphodiesterase (PDE) activities that eliminate 2-5A thereby evading the
      antiviral activity of the OAS/RNase L pathway. These viral proteins are members
      of the eukaryotic-viral LigT-like group of 2H phosphoesterases, so named for the
      presence of 2 conserved catalytic histidine residues. Here, we will review the
      biochemistry, biology, and implications of viral and cellular 2',5'-PDEs that
      degrade 2-5A. In addition, we discuss alternative viral and cellular strategies
      for limiting the activity of OAS/RNase L. 

PMID- 24905205
TI  - Comparative genome-scale analysis of niche-based stress-responsive genes in
      Lactobacillus helveticus strains.
AB  - Next generation sequencing technologies with advanced bioinformatic tools present
      a unique opportunity to compare genomes from diverse niches. The identification
      of niche-specific stress-responsive genes can help in characterizing robust
      strains for multiple applications. In this study, we attempted to compare the
      stress-responsive genes of a potential probiotic strain, Lactobacillus helveticus
      MTCC 5463, and a cheese starter strain, Lactobacillus helveticus DPC 4571, from a
      gut and dairy niche, respectively. Sequencing of MTCC 5463 was done using 454 GS
      FLX, and contigs were assembled using GS Assembler software. Genome analysis was
      done using BLAST hits and the prokaryotic annotation server RAST. The MTCC 5463
      genome carried multiple orthologs of genes governing stress responses, whereas
      the DPC 4571 genome lacked in the number of major stress-response proteins. The
      absence of the bile salt hydrolase gene in DPC 4571 and its presence in MTCC 5463
      clearly indicated niche adaptation. Further, MTCC 5463 carried higher copy
      numbers of genes contributing towards heat, cold, osmotic, and oxidative stress
      resistance as compared with DPC 4571. Through comparative genomics, we could thus
      identify stress-responsive gene sets required to adapt to gut and dairy niches. 

PMID- 24905206
TI  - Implicit theories of writing and their impact on students' response to a SRSD
      intervention.
AB  - BACKGROUND: In the field of intelligence research, it has been shown that some
      people conceive intelligence as a fixed trait that cannot be changed (entity
      beliefs), whereas others conceive it as a malleable trait that can be developed
      (incremental beliefs). What about writing? Do people hold similar implicit
      theories about the nature of their writing ability? Furthermore, are these
      beliefs likely to influence students' response to a writing intervention? AIMS:
      We aimed to develop a scale to measure students' implicit theories of writing
      (pilot study) and to test whether these beliefs influence strategy-instruction
      effectiveness (intervention study). SAMPLE: In the pilot and intervention studies
      participated, respectively, 128 and 192 students (Grades 5-6). METHOD: Based on
      existing instruments that measure self-theories of intelligence, we developed the
      Implicit Theories of Writing (ITW) scale that was tested with the pilot sample.
      In the intervention study, 109 students received planning instruction based on
      the self-regulated strategy development model, whereas 83 students received
      standard writing instruction. Students were evaluated before, in the middle, and
      after instruction. RESULTS: ITW's validity was supported by piloting results and
      their successful cross-validation in the intervention study. In this,
      intervention students wrote longer and better texts than control students.
      Moreover, latent growth curve modelling showed that the more the intervention
      students conceived writing as a malleable skill, the more the quality of their
      texts improved. CONCLUSION: This research is of educational relevance because it
      provides a measure to evaluate students' implicit theories of writing and shows
      their impact on response to intervention.

PMID- 24905207
TI  - Shock wave study of the thermal dissociations of C3F6 and c-C3F6. II.
      dissociation of hexafluorocyclopropane and dimerization of CF2.
AB  - The thermal dissociation of c-C3F6 has been studied in shock waves over the range
      620-1030 K monitoring the UV absorption of CF2. The reaction was studied close to
      its high-pressure limit, but some high-temperature falloff was accounted for.
      Quantum-chemical and kinetic modeling rationalized the experimental data. The
      reaction is suggested to involve the 1,3 biradical CF2CF2CF2 intermediate. CF2
      formed by the dissociation of c-C3F6 dimerizes to C2F4. The measured rate of this
      reaction is also found to correspond to the falloff range. Rate constants for
      2CF2 -> C2F4 as a function of temperature and bath gas concentration [Ar] are
      given and shown to be consistent with literature values for the high-pressure
      rate constants from experiments at lower temperatures and dissociation rate
      constants obtained in the falloff range at higher temperatures. The onset of
      falloff at intermediate temperatures is analyzed. 

PMID- 24905208
TI  - Comparative body compartment composition and in ovo transfer of organophosphate
      flame retardants in North American Great Lakes herring gulls.
AB  - Although recent usage of organophosphate (OP) flame retardants has increased
      substantially, very few studies have reported on OPs in biota including wildlife,
      and essentially there is no information on OP body compartment composition and in
      ovo or in utero transfer for any given wildlife species. Concentrations and
      patterns of 16 OP triesters were presently screened for and/or determined in six
      body compartments from female herring gulls (Larus argentatus; n=8) and the
      separate egg yolk and albumen of their entire clutches of eggs (n=16) (collected
      in 2010 from a Lake Huron colony site, Laurentian Great Lakes of North America).
      Fat (32.3+/-9.8 ng/g wet weight; ww) contained the highest SigmaOP concentration,
      followed by egg yolk (14.8+/-2.4 ng/g ww)~egg albumen (14.8+/-5.9 ng/g ww)>muscle
      (10.9+/-5.1 ng/g ww)?red blood cells (1.00+/-0.62 ng/g ww), whereas in liver,
      blood plasma, and brain all OPs were not detectable. Nine OPs accumulated in
      herring gulls, but the concentrations and proportions of OPs were dependent on
      the body and egg compartment. For example, tris(2-butoxyethyl) phosphate (TBOEP)
      accounted for 66% of the SigmaOP concentration in albumen, but only for 13% in
      yolk. Tri-n-butyl phosphate (TNBP) accounted for 25% of the SigmaOP concentration
      in yolk, but was not detected in albumen. Estimates showed that overall OP
      burdens in the body (3.5 MUg) were greater than in the whole egg (1.2 MUg),
      although depuration via in ovo transfer was substantial.

PMID- 24905211
TI  - Aminated thermoresponsive microgels prepared from the Hofmann rearrangement of
      amides without side reactions.
AB  - Thermoresponsive microgels bearing primary amine groups were prepared by the
      Hofmann rearrangement of methacrylamide groups present in cross-linked NIPMAM (N
      isopropylmethacrylamide) microgels. Most thermoresponsive microgels are based on
      NIPAM (N-isopropylacrylamide). By substituting NIPMAM for NIPAM, and
      methacrylamide for acrylamide, side reactions and the generation of carboxyl
      groups were prevented during the Hofmann reaction. The Hofmann rearrangement is
      sufficiently slow under our conditions (1 h for a 51% conversion) to permit fine
      control of the primary amine contents in the microgels. When starting with
      PNIPMAM microgels containing both methacrylamide and acrylic acid residues, we
      prepared a series of amphoteric microgels spanning a range of amine contents, all
      from a common parent microgel. Therefore, every microgel in the series had the
      same microstructure, cross-link density, and molecular weight. 

PMID- 24905210
TI  - Prediction of postoperative mortality in liver transplantation in the era of MELD
      based liver allocation: a multivariate analysis.
AB  - BACKGROUND AND AIMS: Liver transplantation is the only curative treatment for end
      stage liver disease. While waiting list mortality can be predicted by the MELD
      score, reliable scoring systems for the postoperative period do not exist. This
      study's objective was to identify risk factors that contribute to postoperative
      mortality. METHODS: Between December 2006 and March 2011, 429 patients underwent
      liver transplantation in our department. Risk factors for postoperative mortality
      in 266 consecutive liver transplantations were identified using univariate and
      multivariate analyses. Patients who were <18 years, HU-listings, and split-,
      living related, combined or re-transplantations were excluded from the analysis.
      The correlation between number of risk factors and mortality was analyzed.
      RESULTS: A labMELD >=20, female sex, coronary heart disease, donor risk index
      >1.5 and donor Na+>145 mmol/L were identified to be independent predictive
      factors for postoperative mortality. With increasing number of these risk
      factors, postoperative 90-day and 1-year mortality increased (0-1: 0 and 0%; 2:
      2.9 and 17.4%; 3: 5.6 and 16.8%; 4: 22.2 and 33.3%; 5-6: 60.9 and 66.2%).
      CONCLUSIONS: In this analysis, a simple score was derived that adequately
      identified patients at risk after liver transplantation. Opening a discussion on
      the inclusion of these parameters in the process of organ allocation may be a
      worthwhile venture.

PMID- 24905212
TI  - Successful retrieval of broken coiled guidewire from left atrium during balloon
      mitral valvotomy: a rare complication.
AB  - Abstract Balloon mitral valvotomy (BMV) is the procedure of choice for rheumatic
      mitral stenosis with favorable valve morphology. Fracture of 0.025 inch coiled
      guidewire during BMV is a very rare complication. The various factors which may
      cause this complication are utilization of reused hardware, improper placement of
      guidewire, abnormal angulation between guidewire and dilator with forceful septal
      dilation and rarely manufacturing defect. Here, we report successful retrieval of
      broken 0.025 inch coiled guidewire from left atrium during BMV using 10F
      Amplatzer long sheath without any complication. 

PMID- 24905213
TI  - Predicting supramolecular self-assembly on reconstructed metal surfaces.
AB  - The prediction of supramolecular self-assembly onto solid surfaces is still
      challenging in many situations of interest for nanoscience. In particular, no
      previous simulation approach has been capable to simulate large self-assembly
      patterns of organic molecules over reconstructed surfaces (which have
      periodicities over large distances) due to the large number of surface atoms and
      adsorbing molecules involved. Using a novel simulation technique, we report here
      large scale simulations of the self-assembly patterns of an organic molecule
      (DIP) over different reconstructions of the Au(111) surface. We show that on
      particular reconstructions, the molecule-molecule interactions are enhanced in a
      way that long-range order is promoted. Also, the presence of a distortion in a
      reconstructed surface pattern not only induces the presence of long-range order
      but also is able to drive the organization of DIP into two coexisting homochiral
      domains, in quantitative agreement with STM experiments. On the other hand, only
      short range order is obtained in other reconstructions of the Au(111) surface.
      The simulation strategy opens interesting perspectives to tune the supramolecular
      structure by simulation design and surface engineering if choosing the right
      molecular building blocks and stabilising the chosen reconstruction pattern. 

PMID- 24905214
TI  - Distribution of G (VP7) and P (VP4) genotypes of group A bovine rotaviruses from
      Tunisian calves with diarrhoea.
AB  - AIMS: To investigate the incidence, viral load and genetic diversity of bovine
      rotaviruses strains in Tunisia. METHODS AND RESULTS: A total of 169 faecal
      specimens, collected from diarrhoeic calves from several farms located in the
      central eastern regions of Tunisia, between January 2006 and October 2010, were
      analysed by semi-nested multiplex RT-PCRs for P and G genotypes identification or
      were genotyped by DNA sequencing. Positive samples were tested by TaqMan real
      time RT-PCR to quantify the viral load. Group A bovine rotaviruses were detected
      in 15.4% (26/169) of the total studied cases of diarrhoea. Overall, G10 was the
      predominant G type, detected in 12/26 samples (46.2%) and G6 accounted for 42.3%
      (11/26) while P[11] was the predominant P type, detected in 12/26 samples
      (46.2%). Two P[5] genotypes (7.7%) were found in the collection. Dual G or P
      combination and genotype G8 were not found. The most common VP7/VP4 combinations
      were G6P[11] (30.8%; n = 8) and G10P[11] (11.5%; n = 3). The combination G10P[14]
      was seen in one sample, and partial typing was assessed in 53.8% (n = 14) of the
      cases. The viral load determined by real-time RT-PCR showed an average of 1.68 *
      10(9) genome copies/g of faeces. CONCLUSION: Knowledge of P and G types could
      help us understand the relatedness of animal rotaviruses to viruses causing
      disease in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first time
      that the viral load and P types of bovine rotaviruses have been determined in
      Tunisia, and this study contributes to a better understanding of the epidemiology
      of such viruses circulating in Tunisia. Nevertheless, continuous surveillance is
      necessary to detect the emergence of new variants.

PMID- 24905215
TI  - Superior bactericidal activity of N-bromine compounds compared to their N
      chlorine analogues can be reversed under protein load.
AB  - AIMS: To investigate and compare the bactericidal activity (BA) of active bromine
      and chlorine compounds in the absence and presence of protein load. METHODS AND
      RESULTS: Quantitative killing tests against Escherichia coli and Staphylococcus
      aureus were performed both in the absence and in the presence of peptone with
      pairs of isosteric active chlorine and bromine compounds: hypochlorous and
      hypobromous acid (HOCl and HOBr), dichloro- and dibromoisocyanuric acid,
      chlorantine and bromantine (1,3-dibromo- and 1,3 dichloro-5,5
      dimethylhydantoine), chloramine T and bromamine T (N-chloro- and N-bromo-4
      methylbenzenesulphonamide sodium), and N-chloro- and N-bromotaurine sodium. To
      classify the bactericidal activities on a quantitative basis, an empirical
      coefficient named specific bactericidal activity (SBA), founded on the parameters
      of killing curves, was defined: SBA= mean log reductions/(mean exposure times x
      concentration) [mmol 1(-1) min (-1)]. In the absence of peptone, tests with
      washed micro-organisms revealed a throughout higher BA of bromine compounds with
      only slight differences between single substances. This was in contrast to
      chlorine compounds, whose killing times differed by a factor of more than four
      decimal powers. As a consequence, also the isosteric pairs showed according
      differences. In the presence of peptone, however, bromine compounds showed an
      increased loss of BA, which partly caused a reversal of efficacy within isosteric
      pairs. CONCLUSIONS: In medical practice, weakly oxidizing active chlorine
      compounds like chloramines have the highest potential as topical anti-infectives
      in the presence of proteinaceous material (mucous membranes, open wounds). Active
      bromine compounds, on the other hand, have their chance at insensitive body
      regions with low organic matter, for example skin surfaces. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The expected protein load is one of the most important
      parameters for selection of a suited active halogen compound.

PMID- 24905216
TI  - Enhanced bactericidal action of acidified sodium chlorite caused by the
      saturation of reactants.
AB  - AIMS: Factors affecting the antibacterial action of acidified sodium chlorite
      (ASC), a widely used disinfectant, have not been determined. This study
      investigated the significant factors suggesting efficient production method to
      maximize bactericidal action of ASC. METHODS AND RESULTS: The effects of (i)
      preparation procedures (total three methods); (ii) initial concentrations of
      reactants: sodium chlorite (SC) and citric acid (CTA) (up to maximum solubility
      of each reactant) and (iii) final pH values (3.0 and 2.5) to the bactericidal
      action of ASC were investigated with a fixed final concentration of SC (10 ppm)
      using various foodborne pathogens (Escherichia coli O157:H7, Listeria
      monocytogenes, Salmonella Typhimurium and Staphylococcus aureus). The
      antimicrobial compounds produced and the bactericidal effects depended on the
      preparation procedure and the initial concentrations of the reactants. The ASC
      prepared by premixing highly concentrated reactants (in particular > 40%)
      followed by dilution (dilution after reaction, DAR) was more effective in
      inactivating foodborne pathogens, and it produced higher antimicrobial compound
      (Cl(2) and ClO(2)) yields than the other procedures. A 5-min treatment with ASC,
      produced using the other procedures, resulted in a reduction of < 3.5 log CFU ml(
      1) (Gram positive = 0.18-0.78; Gram negative = 0.03-3.49 log CFU ml(-1)), whereas
      ASC produced with the DAR procedure using the saturated reactants completely
      inactivated all of the test pathogens within 5 min without recovery (initial
      concentration = 6.94-7.08 log CFU ml(-1)). CONCLUSION: The ASC production with
      the DAR procedure using the saturated reactants maximizes both the antimicrobial
      compound yields and bactericidal effects of the ASC solutions. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study will contribute to increase the efficiency of ASC
      treatments for disinfections reducing the effective SC concentrations for
      industrial use.

PMID- 24905217
TI  - Application of r-PFE hyperimmune sera for concurrent detection of Bacillus
      anthracis, Yersinia pestis and staphylococcal enterotoxin B.
AB  - AIM: To evaluate the potential of an intergeneric multidomain recombinant
      chimeric protein for the simultaneous detection of Bacillus anthracis, Yersinia
      pestis and Staphylococcal enterotoxin B. METHODS AND RESULTS: Truncated portions
      of protective antigen (pag) of B. anthracis, fraction 1 capsular antigen (F1) of
      Y. pestis and enterotoxin B (entB) of Staphylococcus aureus were PCR amplified
      and linked each other using ligation-dependent cloning. The fusion gene was codon
      optimized for expression in Escherichia coli and encoded a 55 kDa recombinant PFE
      protein (rPFE). Hyperimmune antiserum raised against rPFE specifically reacted
      individually with the native PA of B. anthracis, F1 antigen of Y. pestis and SEB
      of S. aureus on Western blot analysis as well as in enzyme-linked immunosorbent
      assay (ELISA). For simultaneous detection of these three antigens from culture
      supernatants, common media consisting of BHI broth supplemented with 0.2% xylose
      were used. To assess the detection capability, a known number of these organisms
      (10(8) -10(2) CFU ml(-1)) were experimentally spiked on to the meat and blood
      samples, the polyclonal antibodies were again clearly able to identify all three
      target proteins up to a dilution of 10(5) CFU ml(-1). CONCLUSIONS: This
      recombinant chimeric protein-based immunodetection approach may eventually
      provide advantages over PCR formats during onsite investigations of biological
      emergencies or even during routine testing by laboratories. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The trivalent recombinant PFE protein could be a novel
      intervention for possible diagnosis/detection of potential biological agents
      simultaneously in environmental and clinical samples to reduce the responding
      time and minimize the impact of the bioattack.

PMID- 24905218
TI  - Molecular differentiation of Pantoea stewartii subsp. indologenes from subspecies
      stewartii and identification of new isolates from maize seeds.
AB  - AIMS: Assays to detect Pantoea stewartii from maize seeds should include
      differentiation of P. stewartii subsp. stewartii and P. stewartii subsp.
      indologenes. METHODS AND RESULTS: Previously published PCR primers for the
      identification of P. stewartii subsp. stewartii amplified signals from both
      subspecies using both conventional and quantitative PCR. In MALDI-TOF mass
      spectroscopy analysis with the Biotyper software (Bruker), subspecies stewartii
      and indologenes produced identical score values. Analysis against the Biotyper
      database produced similar score values for both subspecies. From the subtyping
      methods provided by the Biotyper software, only composite correlation indexing
      (CCI) separated both groups. By alignment of 16S rRNA sequences, no subspecies
      distinction was possible. To develop new techniques for the separation of these
      subspecies, the partial sequences of several housekeeping genes were compared.
      The type strains of the two subspecies showed characteristic single-nucleotide
      polymorphisms (SNPs) in the genes galE, glmS and recA. Other reference strains of
      P. stewartii subsp. stewartii followed the same nucleotide pattern, whereas known
      P. stewartii subsp. indologenes strains were different. Based on single
      nucleotide polymorphisms in galE and recA, PCR primers were created to separate
      the subspecies by stepdown PCR analysis. Two putative P. stewartii strains were
      isolated from imported maize seeds. They were not virulent on maize seedlings,
      were positive in the indole assay with Kovacs reagent and identified as P.
      stewartii subsp. indologenes. The subspecies-specific PCR primers confirmed they
      were subspecies indologenes. CONCLUSIONS: By stepdown PCR, P. stewartii subsp.
      indologenes can be differentiated from P. stewartii subsp. stewartii.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A possible detection of P. stewartii subsp.
      stewartii, the causative agent of Stewart's wilt of maize, in plant material by
      immunological or molecular assays must exclude contamination with P. stewartii
      subsp. indologenes, which would create false positives in seed tests and affect
      quarantine measurements.

PMID- 24905219
TI  - The endophyte Verticillium Vt305 protects cauliflower against Verticillium wilt.
AB  - AIMS: To investigate the interaction between cauliflower and the isolate
      VerticilliumVt305, obtained from a field suppressive to Verticillium wilt of
      cauliflower, and to evaluate the ability of VerticilliumVt305 to control
      Verticillium wilt of cauliflower caused by V. longisporum. METHODS AND RESULTS:
      Single and combined inoculations of VerticilliumVt305 and V. longisporum were
      performed on cauliflower seedlings. Symptom development was evaluated, and fungal
      colonization was measured in the roots, hypocotyl and stem with real-time PCR. No
      symptoms were observed after single inoculation of VerticilliumVt305, although it
      colonized the plant tissues. Pre-inoculation of VerticilliumVt305 reduced symptom
      development and colonization of plant tissues by V. longisporum. CONCLUSIONS:
      VerticilliumVt305 is an endophyte on cauliflower plants and showed effective
      biological control of V. longisporum in controlled conditions. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work can contribute to the development of a sustainable
      control measure of V. longisporum in Brassicaceae hosts, which is currently not
      available. Additionally, this study provides evidence for the different roles of
      Verticillium species present in the agro-ecosystem.

PMID- 24905220
TI  - Antimicrobial and plant growth-promoting properties of the cacao endophyte
      Bacillus subtilis ALB629.
AB  - AIMS: To investigate the effects of the endophyte Bacillus subtilisALB629 on the
      growth of cacao seedlings at early developmental stage and to evaluate its
      antimicrobial properties. METHODS AND RESULTS: Germinating cacao seeds were
      inoculated with ALB629, and seedlings growth was evaluated 30 days later.
      Significant increase (P < 0.05) was observed in the root system (up to 30%), leaf
      area (14%) and stem height (7.6%). ALB629 colonized the entire plant, prevailing
      over indigenous micro-organisms. In addition, it was tested in vitro, by pairing
      assays, and showed antagonistic effect against the phytopathogenic fungi
      Moniliophthora perniciosa, Colletotrichum sp. and C. gossypii. When tested in
      cacao-grafting procedure in the field, ALB629 increased the grafting success rate
      (24%), indicating its protective effect. In addition, this Bacillus secretes an
      antagonist compound, as shown by the antifungal activity of the cell-free
      culture. CONCLUSIONS: Bacillus subtilisALB629 promotes cacao root growth, besides
      promoting growth of the aerial part of cacao seedlings. It has antimicrobial
      properties and produces an antifungal compound. SIGNIFICANCE AND IMPACT OF THE
      STUDY: ALB629 presented beneficial characteristics for cacao cultivation, being a
      good biological control agent candidate. Furthermore, it is a potential source of
      antifungal compound with potential for commercial exploitation.

PMID- 24905221
TI  - Probiotic bacteria survive in Cheddar cheese and modify populations of other
      lactic acid bacteria.
AB  - AIMS: Starter lactic acid bacteria in Cheddar cheese face physico-chemical
      stresses during manufacture and ageing that alter their abilities to survive and
      to interact with other bacterial populations. Nonstarter bacteria are derived
      from milk handling, cheese equipment and human contact during manufacture.
      Probiotic bacteria are added to foods for human health benefits that also
      encounter physiological stresses and microbial competition that may mitigate
      their survival during ageing. We added probiotic Lactobacillus acidophilus,
      Lactobacillus casei, Lactobacillus paracasei and Bifidobacterium animalis subsp.
      lactis to full-fat, reduced-fat and low-fat Cheddar cheeses, aiming to study
      their survival over 270 days of ageing and to determine the role of the cheese
      matrix in their survival. METHODS AND RESULTS: Probiotic and other lactic acid
      bacterial populations were enumerated by quantitative PCR using primers
      specifically targeting the different bacterial genera or species of interest.
      Bifidobacteria were initially added at 10(6) CFU g(-1) cheese and survived
      variably in the different cheeses over the 270-day ageing process. Probiotic
      lactobacilli that were added at 10(7) CFU g(-1) cheese and incident nonstarter
      lactobacilli (initially at 10(8) CFU g(-1) cheese) increased by 10- to 100-fold
      over 270 days. Viable bacterial populations were differentiated using propidium
      monoazide followed by species-specific qPCR assays, which demonstrated that the
      starter and probiotic microbes survived over ageing, independent of cheese type.
      Addition of probiotic bacteria, at levels 100-fold below that of starter
      bacteria, modified starter and nonstarter bacterial levels. CONCLUSIONS: We
      demonstrated that starter lactococci, nonstarter lactobacilli and probiotic
      bacteria are capable of surviving throughout the cheesemaking and ageing process,
      indicating that delivery via hard cheeses is possible. Probiotic addition at
      lower levels may also alter starter and nonstarter bacterial survival.
      SIGNIFICANCE AND IMPACT OF THE STUDY: We applied qPCR to study multispecies
      survival and viability and distinctly enumerated bacterial species in commercial
      scale Cheddar cheese manufacture.

PMID- 24905222
TI  - Saccharide breakdown and fermentation by the honey bee gut microbiome.
AB  - The honey bee, the world's most important agricultural pollinator, relies
      exclusively on plant-derived foods for nutrition. Nectar and pollen collected by
      honey bees are processed and matured within the nest through the activities of
      honey bee-derived microbes and enzymes. In order to better understand the
      contribution of the microbial community to food processing in the honey bee, we
      generated a metatranscriptome of the honey bee gut microbiome. The function of
      the microbial community in the honey bee, as revealed by metatranscriptome
      sequencing, resembles that of other animal guts and food-processing environments.
      We identified three major bacterial classes that are active in the gut (gamma
      Proteobacteria, Bacilli and Actinobacteria), all of which are predicted to
      participate in the breakdown of complex macromolecules (e.g. polysaccharides and
      polypeptides), the fermentation of component parts of these macromolecules, and
      the generation of various fermentation products, such as short-chain fatty acids
      and alcohol. The ability of the microbial community to metabolize these carbon
      rich food sources was confirmed through the use of community-level physiological
      profiling. Collectively, these findings suggest that the gut microflora of the
      honey bee harbours bacterial members with unique roles, which ultimately can
      contribute to the processing of plant-derived food for colonies. 

PMID- 24905224
TI  - ER-mitochondria contacts as sites of mitophagosome formation.
AB  - Mitophagy is a degradative process that adapts the quantity and quality of
      mitochondria to the cellular needs. Mitochondria destined for degradation are
      marked by specific receptors that recruit the core autophagic machinery to the
      organellar surface. The organelle is then enclosed by a phagophore (PG) which
      fuses with the lysosome or vacuole where the mitochondrion is degraded. In spite
      of significant progress in recent years, several parts of the molecular machinery
      of mitophagy remain unknown. We used yeast as a model organism to screen for
      novel components and identified the mitochondria-ER tether ERMES (ER-mitochondria
      encounter structure) as a major player contributing to mitophagy and formation of
      mitophagosomes. Tethering of mitochondria to the ER appears to be important to
      supply the growing PG with lipids synthesized in the ER. 

PMID- 24905223
TI  - Dynamics in the cytoadherence phenotypes of Plasmodium falciparum infected
      erythrocytes isolated during pregnancy.
AB  - Pregnant women become susceptible to malaria infection despite their acquired
      immunity to this disease from childhood. The placental sequestration of
      Plasmodium falciparum infected erythrocytes (IE) is the major feature of malaria
      during pregnancy, due to ability of these parasites to bind chondroitin sulfate A
      (CSA) in the placenta through the VAR2CSA protein that parasites express on the
      surface of IE. We collected parasites at different times of pregnancy and
      investigated the adhesion pattern of freshly collected isolates on the three well
      described host receptors (CSPG, CD36 and ICAM-1). Var genes transcription profile
      and VAR2CSA surface-expression were assessed in these isolates. Although adhesion
      of IE to CD36 and ICAM-1 was observed in some isolates, CSA-adhesion was the
      predominant binding feature in all isolates analyzed. Co-existence in the
      peripheral blood of several adhesion phenotypes in early pregnancy isolates was
      observed, a diversity that gradually tightens with gestational age in favour of
      the CSA-adhesion phenotype. Infections occurring in primigravidae were often by
      parasites that adhered more to CSA than those from multigravidae. Data from this
      study further emphasize the specificity of CSA adhesion and VAR2CSA expression by
      parasites responsible for pregnancy malaria, while drawing attention to the
      phenotypic complexity of infections occurring early in pregnancy as well as in
      multigravidae. 

PMID- 24905225
TI  - Optical imaging for monitoring tumor oxygenation response after initiation of
      single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer
      patients.
AB  - PURPOSE: Optical imaging techniques for measuring tissue hemoglobin concentration
      have been recently accepted as a way to assess tumor vascularity and oxygenation.
      We investigated the correlation between early optical response to single-agent
      bevacizumab and treatment outcome. METHODS: Seven patients with advanced or
      metastatic breast cancer were treated with single-agent bevacizumab followed by
      addition of weekly paclitaxel. Optical imaging of patient's breasts was performed
      to measure tumor total hemoglobin concentration (tHb) and oxygen saturation
      (stO2) at baseline and on days 1, 3, 6, 8, and 13 after the first infusion of
      bevacizumab. To assess early metabolic response, 2-deoxy-2-(18F)-fluoro-D-glucose
      (FDG) positron emission tomography/computed tomography (PET/CT), 18F
      fluoromisonidazole (FMISO)-PET/CT, and magnetic resonance imaging were performed
      at baseline and after two cycles of the regimen. RESULTS: Seven patients were
      grouped as responders (n = 4) and nonresponders (n = 3) on the basis of metabolic
      response measured by FDG-PET/CT. The responders showed remarkable tumor shrinkage
      and low accumulations of FMISO tracer relative to those of the nonresponders at
      the completion of two cycles of chemotherapy. Tumors of both groups showed
      remarkable attenuation of mean tHb as early as day 1 after therapy initiation.
      The nonresponders had lower baseline stO2 levels compared with adjacent breast
      tissue stO2 levels along with a pattern of steadily low stO2 levels during the
      observation window. On the other hand, the responders appeared to sustain high
      stO2 levels with temporal fluctuation. CONCLUSIONS: Low tumor stO2 level after
      single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor
      stO2 level could be a predictor of an additional benefit of bevacizumab over that
      provided by paclitaxel.

PMID- 24905226
TI  - Protective effects of astragaloside IV against amyloid beta1-42 neurotoxicity by
      inhibiting the mitochondrial permeability transition pore opening.
AB  - Mitochondrial dysfunction caused by amyloid beta-peptide (Abeta) plays an
      important role in the pathogenesis of Alzheimer disease (AD). Substantial
      evidence has indicated that the mitochondrial permeability transition pore (mPTP)
      opening is involved in Abeta-induced neuronal death and reactive oxygen species
      (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents
      of Astragalus membranaceus, has been reported as an effective anti-oxidant for
      treating neurodegenerative diseases. However, the molecular mechanisms still need
      to be clarified. In this study, we investigated whether AS-IV could prevent
      Abeta1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening.
      The results showed that pretreatment of AS-IV significantly increased the
      viability of neuronal cells, reduced apoptosis, decreased the generation of
      intracellular reactive oxygen species (ROS) and decreased mitochondrial
      superoxide in the presence of Abeta1-42. In addition, pretreatment of AS-IV
      inhibited the mPTP opening, rescued mitochondrial membrane potential (DeltaPsim),
      enhanced ATP generation, improved the activity of cytochrome c oxidase and
      blocked cytochrome c release from mitochondria in Abeta1-42 rich milieu.
      Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase
      3 and increased the expression of Bcl-2 in an Abeta1-42 rich environment. These
      data indicate that AS-IV prevents Abeta1-42-induced SK-N-SH cell apoptosis via
      inhibiting the mPTP opening and ROS generation. These results provide novel
      insights of AS-IV for the prevention and treatment of neurodegenerative disorders
      such as AD. 

PMID- 24905229
TI  - Synthetic approaches to 3-(2-nitroalkyl) indoles and their use to access
      tryptamines and related bioactive compounds.

PMID- 24905227
TI  - Purification and characterization of a novel and robust L-asparaginase having low
      glutaminase activity from Bacillus licheniformis: in vitro evaluation of anti
      cancerous properties.
AB  - L-asparaginase having low glutaminase has been a key therapeutic agent in the
      treatment of acute lymphpoblastic leukemia (A.L.L). In the present study, an
      extracellular L-asparaginase with low glutaminase activity, produced by Bacillus
      licheniformis was purified to homogeneity. Protein was found to be a homotetramer
      of 134.8 KDa with monomeric size of 33.7 KDa and very specific for its natural
      substrate i.e. L-asparagine. The activity of purified L-asparaginase enhanced in
      presence of cations including Na+ and K+, whereas it was moderately inhibited in
      the presence of divalent cations and thiol group blocking reagents. The purified
      enzyme was maximally active over the range of pH 6.0 to 10.0 and temperature of
      40 degrees C and enzyme was stable maximum at pH 9.0 and -20 degrees C. CD
      spectra of L-asparaginase predicted the enzyme to consist of 63.05% alpha-helix
      and 3.29% beta-sheets in its native form with T222 of 58 degrees C. Fluorescent
      spectroscopy showed the protein to be stable even in the presence of more than 3
      M GdHCl. Kinetic parameters Km, Vmax and kcat of purified enzyme were found as
      1.4*10(-5) M, 4.03 IU and 2.68*10(3) s(-1), respectively. The purified L
      asparaginase had cytotoxic activity against various cancerous cell lines viz.
      Jurkat clone E6-1, MCF-7 and K-562 with IC50 of 0.22 IU, 0.78 IU and 0.153 IU
      respectively. However the enzyme had no toxic effect on human erythrocytes and
      CHO cell lines hence should be considered potential candidate for further
      pharmaceutical use as an anticancer drug.

PMID- 24905230
TI  - Effect of amiloride on endoplasmic reticulum stress response in the injured
      spinal cord of rats.
AB  - After traumatic spinal cord injury (SCI), endoplasmic reticulum (ER) stress
      exacerbates secondary injury, leading to expansion of demyelination and reduced
      remyelination due to oligodendrocyte precursor cell (OPC) apoptosis. Although
      recent studies have revealed that amiloride controls ER stress and leads to
      improvement in several neurological disorders including SCI, its mechanism is not
      completely understood. Here, we used a rat SCI model to assess the effects of
      amiloride on functional recovery, secondary damage expansion, ER stress-induced
      cell death and OPC survival. Hindlimb function in rats with spinal cord contusion
      significantly improved after amiloride administration. Amiloride significantly
      decreased the expression of the pro-apoptotic transcription factor CHOP in the
      injured spinal cord and significantly increased the expression of the ER
      chaperone GRP78, which protects cells against ER stress. In addition, amiloride
      treatment led to a significant decrease in ER stress-induced apoptosis and a
      significant increase of NG2-positive OPCs in the injured spinal cord.
      Furthermore, in vitro experiments performed to investigate the direct effect of
      amiloride on OPCs revealed that amiloride reduced CHOP expression in OPCs
      cultured under ER stress. These results suggest that amiloride controls ER stress
      in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present
      study suggests that amiloride may be an effective treatment to reduce ER stress
      induced cell death in the acute phase of SCI. 

PMID- 24905231
TI  - Expression pattern of long non-coding RNAs in renal cell carcinoma revealed by
      microarray.
AB  - BACKGROUND: Recent large-scale transcriptome analyses have found large numbers of
      transcripts, including that of long non-coding RNAs (lncRNAs), which are aberrant
      in various diseases, especially cancers. However, it is not clear whether lncRNAs
      are involved specifically in renal cell carcinoma (RCC). We investigated the
      expression patterns of lncRNAs in five RCC tumor samples (T) relative to those of
      matched adjacent non-tumor tissues (N) via microarray. METHODS: A microarray with
      33,045 lncRNA probes and 30,215 mRNA probes was used to identify deregulated
      lncRNAs in five RCC patients. Furthermore, we confirmed the relative expression
      levels of AK096725 and ENST00000453068 in 70 paired samples by quantitative
      reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The lncRNA
      microarray revealed 27,279 lncRNAs in RCC samples, of which 480 were
      significantly upregulated (P<0.05; T/N>1.5) and 417 were significantly
      downregulated (P<0.05; N/T>1.5) compared with the matched non-tumor samples. In
      addition, 19,995 mRNAs were detected, of which 458 were significantly upregulated
      (P<0.05; T/N>1.5) and 413 were significantly downregulated (P<0.05; N/T>1.5). The
      expression level changes of AK096725 (P = 0.043) and ENST00000453068 (P<0.001) in
      70 paired samples were in accord with the microarray data. CONCLUSIONS: The study
      uncovered expression patterns of lncRNAs in 5 RCC patients, as well as a number
      of aberrant lncRNAs and mRNAs in tumor samples compared with the non-tumor
      tissues. The revelation of an association between AK096725 expression and RCC is
      especially noteworthy. These findings may help to find new biomarkers in RCC.

PMID- 24905232
TI  - The characterization of obese polycystic ovary syndrome rat model suitable for
      exercise intervention.
AB  - OBJECTIVE: To develop a new polycystic ovary syndrome (PCOS) rat model suitable
      for exercise intervention. METHOD: Thirty six rats were randomly divided into
      three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats
      with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6).
      Two kinds of PCOS rat model were made by adjustment diet structure and
      testosterone injection for 28 days. After a successful animal model, PF model
      rats were randomly assigned to three groups: exercise with a continuation of high
      fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n
      = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG)
      and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in
      serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro
      plus 6.0. RESULTS: Body weight, Lee index, FINS increased significantly in PF rat
      model. Serum levels of E2 and T were significantly higher in PF and PO than in
      CO. Ovary organ index and ovarian areas were significant lower in PF than in CO.
      After intervention for 2 weeks, the levels of 1 h postprandial blood glucose
      (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T
      decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was
      significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed
      that the numbers of preantral follicles and atretic follicles decreased
      significantly, and the numbers of antral follicles and corpora lutea increased
      significantly in the rats of PF-EF and PF-EO. CONCLUSION: By combination of high
      fat diet and testosterone injection, the obese PCOS rat model is conformable with
      the lifestyle habits of fatty foods and insufficient exercise, and has metabolic
      and reproductive characteristics of human PCOS. This model can be applied to
      study exercise intervention.

PMID- 24905233
TI  - Global phosphoproteomics of activated B cells using complementary metal ion
      functionalized soluble nanopolymers.
AB  - Engagement of the B cell receptor for antigen (BCR) leads to immune responses
      through a cascade of intracellular signaling events. Most studies to date have
      focused on the BCR and protein tyrosine phosphorylation. Because spleen tyrosine
      kinase, Syk, is an upstream kinase in multiple BCR-regulated signaling pathways,
      it also affects many downstream events that are modulated through the
      phosphorylation of proteins on serine and threonine residues. Here, we report a
      novel phosphopeptide enrichment strategy and its application to a comprehensive
      quantitative phosphoproteomics analysis of Syk-dependent downstream signaling
      events in B cells, focusing on serine and threonine phosphorylation. Using a
      combination of the Syk inhibitor piceatannol, SILAC quantification, peptide
      fractionation, and complementary PolyMAC-Ti and PolyMAC-Zr enrichment techniques,
      we analyzed changes in BCR-stimulated protein phosphorylation that were dependent
      on the activity of Syk. We identified and quantified over 13,000 unique
      phosphopeptides, with a large percentage dependent on Syk activity in BCR
      stimulated B cells. Our results not only confirmed many known functions of Syk,
      but more importantly, suggested many novel roles, including in the ubiquitin
      proteasome pathway, that warrant further exploration.

PMID- 24905234
TI  - Himalayan origin and evolution of Myricaria (Tamaricaeae) in the neogene.
AB  - BACKGROUND: Myricaria consists of about twelve-thirteen species and occurs in
      Eurasian North Temperate zone, most species in the Qinghai-Tibet Plateau (QTP)
      and adjacent areas. METHODOLOGY/PRINCIPAL FINDINGS: Twelve species of Myricaria
      plus two other genera Tamarix and Reaumuria in Tamaricaceae, were sampled, and
      four markers, ITS, rps16, psbB-psbH, and trnL-trnF were sequenced. The relaxed
      Bayesian molecular clock BEAST method was used to perform phylogenetic analysis
      and molecular dating, and Diva, S-Diva, and maximum likelihood Lagrange were used
      to estimate the ancestral area. The results indicated that Myricaria could be
      divided into four phylogenetic clades, which correspond to four sections within
      the genus, of them two are newly described in this paper. The crown age of
      Myricaria was dated to early Miocene ca. 20 Ma, at the probable early uplifting
      time of the Himalayas. The Himalayas were also shown as the center of origin for
      Myricaria from the optimization of ancestral distribution. Migration and
      dispersal of Myricaria were indicated to have taken place along the Asian
      Mountains, including the Himalayas, Kunlun, Altun, Hendukosh, Tianshan, Altai,
      and Caucasus etc., westward to Europe, eastward to Central China, and northward
      to the Mongolian Plateau. CONCLUSIONS/SIGNIFICANCE: Myricaria spatiotemporal
      evolution presented here, especially the Himalayan origin at early Miocene ca. 20
      Ma, and then migrated westward and eastward along the Asian mountains, offers a
      significant evolutionary case for QTP and Central Asian biogeography.

PMID- 24905235
TI  - The potential cost-effectiveness of quadrivalent versus trivalent influenza
      vaccine in elderly people and clinical risk groups in the UK: a lifetime multi
      cohort model.
AB  - OBJECTIVE: To estimate the potential cost-effectiveness of quadrivalent influenza
      vaccine compared with trivalent influenza vaccine in the UK. METHODS: A lifetime,
      multi-cohort, static Markov model was constructed, with nine age groups each
      divided into healthy and at-risk categories. Influenza A and B were accounted for
      separately. The model was run in one-year cycles for a lifetime (maximum age: 100
      years). The analysis was from the perspective of the UK National Health Service.
      Costs and benefits were discounted at 3.5%. 2010 UK vaccination policy
      (vaccination of people at risk and those aged >=65 years) was applied. Herd
      effect was not included. Inputs were derived from national databases and
      published sources where possible. The quadrivalent influenza vaccine price was
      not available when the study was conducted. It was estimated at L6.72,15% above
      the trivalent vaccine price of L5.85. Sensitivity analyses used an incremental
      price of up to 50%. RESULTS: Compared with trivalent influenza vaccine, the
      quadrivalent influenza vaccine would be expected to reduce the numbers of
      influenza cases by 1,393,720, medical visits by 439,852 complications by 167,357,
      hospitalisations for complications by 26,424 and influenza deaths by 16,471. The
      estimated base case incremental cost-effectiveness ratio (ICER) was
      L5,299/quality-adjusted life-year (QALY). Sensitivity analyses indicated that the
      ICER was sensitive to changes in circulation of influenza virus subtypes and
      vaccine mismatch; all other parameters had little effect. In 96% of simulations
      the ICER was <L20,000/QALY. Since this analysis was completed, quadrivalent
      influenza vaccine has become available in the UK at a list price of L9.94. Using
      this price in the model, the estimated ICER for quadrivalent compared with
      trivalent vaccination was L27,378/QALY, still within the NICE cost-effectiveness
      threshold (L20,000-L30,000). CONCLUSIONS: Quadrivalent influenza vaccine could
      reduce influenza disease burden and would be cost-effective compared with
      trivalent influenza vaccine in elderly people and clinical risk groups in the UK.

PMID- 24905236
TI  - Major depression and suicide attempts in patients with liver disease in the
      United States.
AB  - BACKGROUND & AIMS: Depression is common in patients with liver disease. Moreover,
      alcohol use is intricately linked with both major depression and liver disease,
      and has also been linked with suicidal behaviours, suggesting that the alcohol
      use may have an intermediate role in the relationship between liver disease and
      major depression or suicidal behaviours. This study presents nationally
      representative data on the prevalence of major depression in patients with liver
      disease in the United States and its association with suicide attempts. METHODS:
      Data were drawn from the 2001-2002 National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC). The NESARC is a survey of 43 093 adults aged 18
      years and older in the United States. Medically recognized liver diseases were
      self-reported, and diagnoses of major depression were based on the Alcohol Use
      Disorder and Associated Disabilities Interview Schedule-DSM-IV version. RESULT:
      The prevalence of liver disease was estimated at 0.7%. Respondents with a liver
      disease reported 12-month rates of major depression (17.2%) that were
      significantly higher than among respondents without liver disease (7.0%; Adjusted
      OR:2.2; CI: 1.2-4.1). Lifetime rates of suicide attempts among participants with
      a major depression were also higher in participants with a liver disease (33.2%)
      than among respondents without liver disease (13.7%; OR: 3.1; CI: 1.3-7.6).
      CONCLUSIONS: Liver diseases are associated with major depression and suicide
      attempts among adults in the community. Adjustment for the amount of alcohol used
      or sociodemographical factors did not explain the observed association of liver
      disease with both major depression and suicide attempts.

PMID- 24905237
TI  - Chronic light deprivation inhibits appetitive associative learning induced by
      ethanol and its respective c-Fos and pCREB expression.
AB  - To address the role of mixed anxiety/mood disorder on appetitive associative
      learning, we verify whether previous chronic light deprivation changes ethanol
      induced conditioned place preference and its respective expression of c-Fos and
      pCREB, markers of neuronal activity and plasticity. The experimental group was
      maintained in light deprivation for 24 h for a period of 4 wk. Subsequently, it
      was adapted to a standard light-dark cycle for 1 wk. As a control, some mice were
      maintained in standard cycle for a period of 4 wk (Naive group). Then, all
      animals were submitted to behavioral tests to assess emotionality: elevated plus
      maze; open field; and forced swim. After that, they were submitted to ethanol
      induced conditioned place preference. Ninety minutes after the place preference
      test, they were perfused, and their brains processed for c-Fos and pCREB
      immunohistochemistry. Light deprivation induced anxiety-like trait (elevated plus
      maze), despair (forced swim), and hyperlocomotion (open field), common features
      seen in other animal models of depression. Ethanol-induced conditioned place
      preference was accompanied by increases on c-Fos and pCREB in the hippocampus,
      prefrontal cortex and striatum. Interestingly, mice previously submitted to light
      deprivation did not develop either acquisition and/or expression of ethanol
      induced conditioned place preference or increases in c-Fos and pCREB. Therefore,
      chronic light deprivation mimics several behavioral aspects of other animal
      models of depression. Furthermore, it could be useful to study the neurochemical
      mechanisms involved in the dual diagnosis. However, given its likely deleterious
      effects on appetitive associative memory, it should be used with caution to
      investigate the cognitive aspects related to the dual diagnosis. 

PMID- 24905238
TI  - Stability studies of antiandrogenic compounds in Curcuma aeruginosa Roxb.
      extract.
AB  - OBJECTIVES: Curcuma aeruginosa Roxb. extract is a 5alpha-reductase antagonist
      that can be used to treat hair loss. We aimed to study the stability of
      antiandrogenic constituents, germacrone and other sesquiterpene components in the
      extract. METHODS: Germacrone and the extract were analyzed as solid forms or
      solublized with polyethylene glycol-40 (PEG-40) or methanol using high
      performance liquid chromatography and gas chromatography with flame ionization
      detector. The effects of pH, temperature and light on their stability were
      studied. KEY FINDINGS: Degradation of antiandrogenic compounds in C. aeruginosa
      was highly sensitive to temperature especially pure anhydrous germacrone, which
      was completely lost within 3 days at 45 degrees C. Curiously, degradation was
      slower than as a dried extract. Paradoxically, when solubilized with PEG-40, it
      was largely intact even after 90 days at 45 degrees C. The MS spectrum of a major
      degradation product suggested that it was elemenone probably produced by Cope
      rearrangement. Two other putative degradation products were germacrone-1,10
      epoxide and germacrone-4,5-epoxide suggesting that oxidation of double bonds was
      an important mechanism. Germacrone stability was unaffected by pH (2.0-9.0) but
      only as dried extract it was slightly degraded by light. CONCLUSION:
      Antiandrogenic constituents of C. aeruginosa were instable at high temperature
      and in solid form. Thus, the extract would be optimately stored as a solution or
      otherwise as solid form at low temperature.

PMID- 24905240
TI  - Organocatalytic chemo- and regioselective oxyarylation of styrenes via a cascade
      reaction: remote activation of hydroxyl groups.
AB  - The first organocatalytic oxyarylation of styrenes has been established through a
      cascade of vinylogous Michael addition/alkoxyl transfer reactions of o- or p
      hydroxylstyrenes with quinone imine ketals. The process leads to a highly chemo-
      and regioselective oxyarylation of styrenes and provides access to m-alkylated
      anilines in generally high yields and excellent diastereoselectivity (up to 99%
      yield, >95:5 dr). An investigation of the reaction pathway revealed that the
      existence and position of the hydroxyl group of styrene played crucial roles in
      the cascade reaction, suggesting that the two reactants were simultaneously
      activated by binaphthyl-derived phosphoric acid via hydrogen bonding interactions
      and long-distance conjugative effects. In addition, the activating group of the
      hydroxyl functionality in the products can be easily removed or transformed,
      demonstrating the applicability and utility of this strategy in styrene
      oxyarylation and in the synthesis of styrene-based compounds. 

PMID- 24905239
TI  - Risk factors of hospital readmission after radical cystectomy and urinary
      diversion: analysis of a large contemporary series.
AB  - OBJECTIVES: To determine the incidence, risk factors and causes of hospital
      readmission in a large series of patients who underwent radical cystectomy (RC)
      and urinary diversion. PATIENTS AND METHODS: We retrospectively analysed the data
      of 1000 patients who underwent RC and urinary diversion between January 2004 and
      September 2009 in our tertiary referral centre. Patients stayed in hospital for
      21 and 11 days for orthotopic and ileal conduit diversions, respectively. The
      primary outcome was the development of a complication requiring hospital
      readmission at <=3 months (early) and >3 months (late). Causes of hospital
      readmissions were categorised according to frequency of readmissions. Predictors
      were determined using univariate and multivariate logistic regression models.
      RESULTS: In all, 895 patients were analysed excluding 105 patients because of
      perioperative mortality and loss to follow-up. Early and late readmissions
      occurred in 8.6% and 11% patients, respectively. The commonest causes of first
      readmission were upper urinary tract obstruction (UUO, 13%) and pyelonephritis
      (12.4%) followed by intestinal obstruction (11.9%) and metabolic acidosis
      (11.3%). The development of postoperative high-grade complications (odds ratio
      [OR] 1.955; 95% confidence interval [CI] 1.254-3.046; P = 0.003) and orthotopic
      bladder substitution (OR 1.585; 95% CI 1.095-2.295; P = 0.015) were independent
      predictors for overall hospital readmission after RC. Postoperative high-grade
      complications (OR 2.488; 95% CI 1.391-4.450; P = 0.002), orthotopic bladder
      substitution (OR 2.492; 95% CI 1.423-4.364; P = 0.001) and prolonged hospital
      stay (OR 1.964; 95% CI:1.166-3.308; P = 0.011) were independent predictors for
      early readmission while hypertension (OR 1.670; 95% CI 1.007-2.769; P = 0.047)
      was an independent predictor for late readmission. CONCLUSION: Hospital
      readmissions are a significant problem after RC. In the present study, UUO,
      pyelonephritis, metabolic acidosis and intestinal obstruction were the main
      causes of readmission. Orthotopic bladder substitution and development of
      postoperative high-grade complications were significant predictors for overall
      readmission.

PMID- 24905243
TI  - The public health impacts of climate change in the former Yugoslav Republic of
      Macedonia.
AB  - Projected climatic changes for the former Yugoslav Republic of Macedonia for the
      period 2025-2100 will be most intense in the warmest period of the year with more
      frequent and more intense heat-waves, droughts and flood events compared with the
      period 1961-1990. The country has examined their vulnerabilities to climate
      change and many public health impacts have been projected. A variety of
      qualitative and quantitative methodologies were used in the assessment:
      literature reviews, interviews, focus groups, time series and regression
      analysis, damage and adaptation cost estimation, and scenario-based assessment.
      Policies and interventions to minimize the risks and development of long-term
      adaptation strategies have been explored. The generation of a robust evidence
      base and the development of stakeholder engagement have been used to support the
      development of an adaptation strategy and to promote adaptive capacity by
      improving the resilience of public health systems to climate change. Climate
      change adaptation has been established as a priority within existing national
      policy instruments. The lessons learnt from the process are applicable to
      countries considering how best to improve adaptive capacity and resilience of
      health systems to climate variability and its associated impacts. 

PMID- 24905241
TI  - A qualitative process evaluation of classroom-based cognitive behaviour therapy
      to reduce adolescent depression.
AB  - Small scale trials indicate that classroom-based Cognitive Behaviour Therapy
      (CBT) for adolescents has good reach and can help prevent depression. However,
      under more diverse everyday conditions, such programmes tend not to show such
      positive effects. This study examined the process of implementing a classroom
      based CBT depression prevention programme as part of a large (n = 5,030)
      randomised controlled trial across eight UK secondary schools which was not found
      to be effective (PROMISE, ISRCTN19083628). The views of young people (n = 42),
      teachers (n = 12) and facilitators (n = 16) involved in the Resourceful
      Adolescent Programme (RAP) were obtained via focus groups and interviews which
      were thematically analysed. The programme was considered to be well structured
      and contain useful content, particularly for younger pupils. However, challenges
      associated with implementation were its age appropriateness for all year groups,
      its perceived lack of flexibility, the consistency of quality of delivery, the
      competing demands for teacher time and a culture where academic targets were
      prioritised over personal, social and health education. Whilst schools are
      convenient locations for introducing such programmes and allow good reach, the
      culture around improving well-being of young people in schools, increasing
      engagement with teachers and young people and sustaining such programmes are
      issues that need addressing. 

PMID- 24905244
TI  - Higher urinary heavy metal, phthalate, and arsenic but not parabens
      concentrations in people with high blood pressure, U.S. NHANES, 2011-2012.
AB  - Link between environmental chemicals and human health has emerged but not been
      completely examined in risk factors. Therefore, it was aimed to study the
      relationships of different sets of urinary environmental chemical concentrations
      and risk of high blood pressure (BP) in a national, population-based study. Data
      were retrieved from United States National Health and Nutrition Examination
      Surveys, 2011-2012 including demographics, BP readings, and urinary environmental
      chemical concentrations. Analyses included chi-square test, t-test and survey
      weighted logistic regression modeling. After full adjustment (adjusting for
      urinary creatinine, age, sex, ethnicity, and body mass index), urinary cesium (OR
      1.56, 95%CI 1.11-2.20, P = 0.014), molybden (OR 1.46, 95%CI 1.06-2.01, P =
      0.023), manganese (OR 1.42, 95%CI 1.09-1.86, P = 0.012), lead (OR 1.58, 95%CI
      1.28-1.96, P < 0.001), tin (OR 1.44, 95%CI 1.25-1.66, P < 0.001), antimony (OR
      1.39, 95%CI 1.10-1.77, P = 0.010), and tungsten (OR 1.49, 95%CI 1.25-1.77, P <
      0.001) concentrations were observed to be associated with high BP. People with
      higher urinary mono-2-ethyl-5-carboxypentyl phthalate (OR 1.33, 95%CI 1.00-1.62,
      P = 0.006), mono-n-butyl phthalate (OR 1.35, 95%CI 1.13-1.62, P = 0.002), mono-2
      ethyl-5-hydroxyhexyl (OR 1.25, 95%CI 1.05-1.49, P = 0.014), mono-n-methyl
      phthalate (OR 1.26, 95%CI 1.07-1.48, P = 0.007), mono-2-ethyl-5-oxohexyl (OR
      1.25, 95%CI 1.07-1.48, P = 0.009), and monobenzyl phthalate (OR 1.40, 95%CI 1.15
      1.69, P = 0.002) tended to have high BP as well. However, there are no clear
      associations between environmental parabens and high BP, nor between pesticides
      and high BP. In addition, trimethylarsine oxide (OR 2.47, 95%CI 1.27-4.81, P =
      0.011) and dimethylarsonic acid concentrations (OR 1.42, 95%CI 1.12-1.79, P =
      0.006) were seen to be associated with high BP. In sum, urinary heavy metal,
      phthalate, and arsenic concentrations were associated with high BP, although the
      causal effect cannot be established from the current study design. Elimination of
      environmental chemicals in humans would still need to be continued. 

PMID- 24905245
TI  - A global, multi-disciplinary, multi-sectorial initiative to combat leptospirosis:
      Global Leptospirosis Environmental Action Network (GLEAN).
AB  - Leptospirosis has emerged as a major public health problem in both animals and
      humans. The true burden of this epidemic and endemic disease is likely to be
      grossly under-estimated due to the non-specific clinical presentations of the
      disease and the difficulty of laboratory confirmation. The complexity that
      surrounds the transmission dynamics, particularly in epidemic situations,
      requires a coordinated, multi-disciplinary effort. Therefore, the Global
      Leptospirosis Environmental Action Network (GLEAN) was developed to improve
      global and local strategies of how to predict, prevent, detect, and intervene in
      leptospirosis outbreaks in order to prevent and control leptospirosis in high
      risk populations. 

PMID- 24905247
TI  - Renewing partnerships.

PMID- 24905248
TI  - The "carrion cast": an intracavernosal antimicrobial cast for the treatment of
      infected penile implant.

PMID- 24905246
TI  - Are we driving our kids to unhealthy habits? Results of the active healthy kids
      Canada 2013 report card on physical activity for children and youth.
AB  - This article examines the time trends in patterns of school travel mode among
      Canadian children and youth to inform the Active Transportation (AT) indicator of
      the 2013 Active Healthy Kids Canada Report Card on Physical Activity for Children
      and Youth. The AT grade was assigned based on a comprehensive synthesis of the
      2000 and 2010 Physical Activity Monitor studies from the Canadian Fitness and
      Lifestyle Research Institute and the 1992, 1998, 2005, and 2010 General Social
      Survey from Statistics Canada. The results showed that in 2013, AT was graded a
      D, because less than half of Canadian children and youth used only active modes
      of transportation to get to and from school. The proportion of Canadian children
      and youth who used only inactive modes of transportation for school travel
      increased significantly from 51% to 62% over the last decade. Children and youth
      from larger communities and those with lower household income levels were
      significantly more likely to use AT than those living in smaller communities and
      those in higher income households, respectively. In conclusion, motorized
      transport for school travel has increased steadily over the last decade across
      Canada. Regional and socio-demographic disparities should be considered in
      efforts to increase the number of children using AT. 

PMID- 24905250
TI  - Will I have a heart attack or stroke if I take testosterone therapy?

PMID- 24905251
TI  - The assessment and management of cancer cachexia: hypogonadism and
      hypermetabolism among supportive and palliative care patients.
AB  - PURPOSE OF REVIEW: To update the healthcare providers on the potential
      contribution of increased basal metabolic rate, hypermetabolism, and low
      testosterone in the development of weight loss in cancer patients. RECENT
      FINDINGS: Cancer cachexia, the loss of skeletal muscle with or without the loss
      of fat, is a multifactorial syndrome. A wide variation in the frequency of
      hypermetabolism exists in cancer patients and can only be accurately identified
      by an indirect calorimeter. The frequency of hypermetabolism increases depending
      on the histology and stage of tumor, associated with the presence of an acute
      inflammatory response, and is often accompanied by weight loss. Hypogonadism, as
      a result of chemotherapy, radiation treatment, or the use of opioids to treat
      chronic pain, is frequently noted in male cancer patients and has been reported
      to be also associated with anorexia and weight loss. SUMMARY: Cancer patients may
      develop weight loss, cachexia, which can be distressing for both patients and
      their family. Treatments directed at reducing the basal metabolic rate and
      supplementation of testosterone in hypogonadic male patients may have the
      potential to improve lean body mass, but more research is needed.

PMID- 24905253
TI  - Retinal structural changes in a case of spontaneous resolution of vitreomacular
      traction syndrome: multimodal retinal imaging approach.
AB  - PURPOSE: Retinal structural changes in a case of spontaneous resolution of
      vitreomacular traction (VMT) syndrome were followed by means of multimodal
      retinal imaging approach. METHODS: Confocal scanning laser ophthalmoscopy (cSLO)
      including digital infrared and blue reflectance (BR) imaging and spectral-domain
      optical coherence tomography (SD-OCT) were performed in a young man with VMT
      syndrome. RESULTS: At the time of diagnosis, multimodal retinal imaging
      documented outer retina abnormalities linked to VMT. At 1 month follow-up visit,
      improvement of best-corrected visual acuity and resolution of metamorphopsia were
      accompanied by documentation of VMT resolution and outer retina restoration.
      CONCLUSIONS: Both cSLO and SD-OCT imaging, particularly BR and en face OCT
      adapted to the outer plexiform layer contour, allowed to depict outer retina
      changes in the course of VMT resolution. A strict correlation between topographic
      BR images and en face OCT scans was evident.

PMID- 24905252
TI  - Efficient modulation of gamma-aminobutyric acid type A receptors by piperine
      derivatives.
AB  - Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor)
      receptors and modulates gamma-aminobutyric acid type A receptors (GABAAR). We
      have synthesized a library of 76 piperine analogues and analyzed their effects on
      GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were
      expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were
      established to identify structural elements essential for efficiency and potency.
      Efficiency of piperine derivatives was significantly increased by exchanging the
      piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p
      methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by
      replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N
      bistrifluoroethyl groups. Linker modifications did not substantially enhance the
      effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4
      pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced
      chloride current modulation (IGABA-max = 1673% +/- 146%, EC50 = 51.7 +/- 9.5
      MUM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide]
      displayed the highest potency (EC50 = 13.8 +/- 1.8 MUM, IGABA-max = 760% +/-
      47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine
      and thus may serve as a starting point for developing novel GABAAR modulators.

PMID- 24905255
TI  - Correlation of intraocular pressure with central corneal thickness in premature
      and full-term newborns.
AB  - PURPOSE: To evaluate the relation of central corneal thickness (CCT) and
      intraocular pressure (IOP) in preterm and full-term newborns. METHODS: The study
      included preterm infants who were admitted to the neonatal intensive care unit. A
      group of consecutive full-term newborns served as control group. Linear and
      multiple regression analysis were carried out to assess the association of IOP
      with sex, gestational/postconceptional age, birthweight, mean oxygenation time,
      stages of retinopathy of prematurity (ROP), and CCT. Linear and multiple
      regression analysis were also carried out to assess the association of CCT with
      sex, gestational/postconceptional age, birthweight, mean oxygenation time, and
      stages of ROP. RESULTS: Mean IOP was 17.5 +/- 2.1 mm Hg in premature newborns and
      16.3 +/- 1.9 mm Hg in full-term newborns (p = 0.001). Mean CCT was 576.5 +/- 16.8
      um in premature newborns and 562.7 +/- 18.5 mm in full-term newborns (p = 0.000).
      Intraocular pressure was not correlated with CCT in preterm infants. Intraocular
      pressure was moderately correlated with CCT in full-term infants. Sex,
      postconceptional age at birth and at measurement, age after birth at measurement,
      birthweight, mean oxygenation time, and stage of ROP were not related to IOP.
      Central corneal thickness was not correlated with any parameter. CONCLUSIONS: Our
      results showed that the CCT does not affect IOP significantly in preterm infants.
      More prospective studies are needed for determining the effect of CCT and other
      ocular and systemic factors on IOP in preterm infants.

PMID- 24905254
TI  - Yellow micropulse laser in diabetic macular edema: a short-term pilot study.
AB  - PURPOSE: To evaluate the effects of yellow micropulse laser in eyes with diabetic
      macular edema (DME). METHODS: In this retrospective interventional case series,
      22 eyes of 17 patients with visual impairment secondary to persistent DME
      received one single session of yellow micropulse laser. Patients were divided
      into 2 groups: group 1, naive eyes; and group 2, previously treated eyes. Main
      outcome measures included changes in central retinal thickness (CRT) and best
      corrected visual acuity (BCVA). Possible atrophic changes of the retinal pigment
      epithelium as a result of yellow micropulse laser application were evaluated with
      fundus autofluorescence. RESULTS: At baseline, the mean logMAR BCVA was 0.39 +/-
      0.18 and the mean CRT was 361.8 +/- 70.95. The mean BCVA improved to 0.31 +/-
      0.19 (p = 0.0091) and 0.31 +/- 0.19 (p = 0.0078) at 3 and 6 months of follow-up,
      respectively. The mean CRT improved to 331.3 +/- 48.46 (p<0.0001) and 328.1 +/-
      53.25 (p<0.0001) at 3 and 6 months of follow-up. Subgroup analysis showed that
      only in naive eyes was there a beneficial effect on visual acuity and central
      macular thickness. CONCLUSIONS: In eyes with DME, yellow micropulse laser
      produces a statistically significant improvement in BCVA and CRT in the short
      term.

PMID- 24905257
TI  - Wetlands as long-term sources of metals to receiving waters in mining-impacted
      landscapes.
AB  - Wetlands are prevalent in the Sudbury, Ontario region and often operate at the
      interface between terrestrial and aquatic ecosystems, modifying water chemistry
      and potentially affecting the recovery of impacted lakes. The deposition of
      metals and sulphur in Sudbury in 2010-2012 was far below that reported in the
      1970's, but still higher than background values. Wetlands in the area have
      accumulated large quantities of metals, and high concentrations of these metals
      in streams occurred primarily in response to SO4-related acidification events or
      associated with high dissolved organic carbon production in early summer.
      Concentrations of most metals in streams exceeded provincial guidelines and
      fluxes of some metals from catchments exceeded deposition inputs to lakes by as
      much as 12 times. The release of metals long after emissions reductions have been
      achieved must be considered in ecosystem recovery studies, particularly as dry
      conditions may become more prevalent in boreal regions affected by mining. 

PMID- 24905256
TI  - Atmospheric polycyclic aromatic hydrocarbons in rural and urban areas of northern
      China.
AB  - Air pollution in rural China has often been ignored, especially for the less
      developed west China. Atmospheric polycyclic aromatic hydrocarbons (PAHs) were
      measured monthly at 11 rural sites (5 rural villages and 6 rural fields) together
      with 7 urban stations in northern China between April 2010 and March 2011. PAH
      concentrations at rural village sites were similar to those in urban areas and
      significantly higher than those in rural fields, indicating severe contamination
      in rural villages. PAH concentrations in the west were similar to those in the
      more developed North China Plain, and higher than those along the coast. Such a
      geographical distribution is mainly caused by the differences in residential
      energy consumption and meteorological conditions, which can explain approximately
      48% of the total variation in PAH concentrations. With heavy dependence on
      biofuel combustion for heating, seasonality in rural areas is more profound than
      that in urban areas. 

PMID- 24905258
TI  - On parafunctional considerations in implant therapy.

PMID- 24905259
TI  - Should occlusal splints be a routine prescription for diagnosed bruxers
      undergoing implant therapy?
AB  - Despite the documented excellent clinical performance of dental implants,
      concerns linger regarding the best way to protect the restored dentition in
      patients with bruxism. This is because of the risk of occlusal overload that is
      reported to cause biological and biomechanical failures in the implant-prosthesis
      system. To better distribute occlusal loads to the rigid components of the
      prosthesis and to the interface between bone and implant during parafunctional
      movements, several dentists prescribe acrylic resin occlusal splints for
      nocturnal use by patients considered at risk. However, it is unclear whether this
      recommendation is based on scientific evidence or expert clinical opinion. This
      report reflects our effort to employ the systematic review protocol to assess
      whether there is scientific evidence to recommend an occlusal splint in bruxers
      after implant therapy. 

PMID- 24905260
TI  - Immediate versus delayed loading of dental implants in edentulous patients'
      maxillae: a 6-year prospective study.
AB  - PURPOSE: This study compared the surgical protocol efficacy of immediate and
      delayed implant loading in edentulous maxillae opposed by natural or restored
      mandibular dentitions over an observational period of 6 years or longer. The
      selected outcome determinants included individual implant survival data,
      progressive measurements of peri-implant bone resorption, prosthodontic survival
      and success data, and report of complications. MATERIALS AND METHODS: A
      convenience sample of 49 patients requiring fixed implant-supported maxillary
      prostheses was split into two groups. The test group (34 patients) was treated
      according to the Columbus Bridge Protocol, which prescribes the insertion of four
      to six implants, including distally tilted implants, and load within 24 hours.
      The control group (15 patients) was treated via a two-stage surgical protocol of
      6 to 9 straight implants that were loaded a mean 8.75 months after stage-one
      implant surgery. Two hundred sixty implants (test: n = 163, control: n = 97) were
      placed, and all subjects were ultimately treated with screw-retained full-arch
      prostheses. RESULTS: Two patients dropped out (one in the test group and one in
      the control group) by the time of the scheduled sixth annual visit. The other
      patients were followed up for 75.2 months (range: 72 to 90 months). At the 6-year
      follow-up, no differences in implant cumulative survival rates were found between
      groups. Significantly less bone loss was found in the test group (mean: 1.62 mm)
      compared with the control group (mean: 2.44 mm). All of the original prostheses
      were maintained throughout the study's observation period and were functioning
      satisfactorily at each patient's last recall appointment. CONCLUSION: Patients
      who received immediate and delayed implant loading in their edentulous maxillae
      demonstrated similar survival outcomes. However, less marginal bone loss was
      recorded around the immediately loaded implants over the study's 6-year follow-up
      period.

PMID- 24905261
TI  - Effect of chemical disinfection on the surface roughness of hard denture base
      materials: a systematic literature review.
AB  - PURPOSE: To assess the effect of chemical disinfection procedures on the surface
      roughness of hard denture base materials. MATERIALS AND METHODS: A systematic
      literature review was conducted using five electronic databases (Medline,
      Cochrane Library, OpenGrey, Lilac, and Google Scholar) along with hand searching
      of the bibliographies of all located articles. RESULTS: The review yielded 193
      articles. This number was reduced to 25 by using defined inclusion and exclusion
      criteria. Only one in vivo study was included; all others were in vitro
      evaluations. For every disinfecting agent, studies were found that reported
      surface alteration after chemical disinfection. The current literature suggests
      that changes in roughness might be more often associated with sodium perborate
      (three out of three studies with positive correlation) and less often with
      chlorhexidine digluconate and glutaraldehyde (two out of seven and one out of
      four studies with positive correlation, respectively). Because only single
      studies were found for glycine-type amphoteric surfactant solution, enzyme
      solution, ethanol, berberine hydrochloride, chlorine, reactive oxygen species,
      peracetic acid, cetylpyridinium chloride, and citric acid, no conclusions can be
      drawn about these disinfectants. CONCLUSIONS: Physical surface alteration is only
      one aspect when deciding on the use of chemical disinfection procedures. More
      research is needed to clarify whether these procedures can be recommended to
      patients.

PMID- 24905262
TI  - Patient satisfaction with single-tooth implant therapy in the esthetic zone.
AB  - This prospective study assessed patient satisfaction before and after single
      tooth implant therapy in the esthetic zone. Before implant therapy, patients wore
      an acrylic resin tissue-supported removable partial denture (RPD). A total of 153
      patients were included. Self-administered questionnaires regarding function,
      comfort, and esthetics were used to measure patient satisfaction with the RPD and
      with the implant at 6 and 18 months post-implant placement. Overall satisfaction
      was explored with a visual analog scale. It was suggested that patient
      satisfaction with a single-tooth implant in the esthetic zone is high and it
      improved when compared with an RPD that patients wore before implant treatment. 

PMID- 24905264
TI  - Accuracy of medical subject heading indexing of dental survival analyses.
AB  - PURPOSE: To assess the Medical Subject Headings (MeSH) indexing of articles that
      employed time-to-event analyses to report outcomes of dental treatment in
      patients. MATERIALS AND METHODS: Articles published in 2008 in 50 dental journals
      with the highest impact factors were hand searched to identify articles reporting
      dental treatment outcomes over time in human subjects with time-to-event
      statistics (included, n = 95), without time-to-event statistics (active controls,
      n = 91), and all other articles (passive controls, n = 6,769). The search was
      systematic (kappa 0.92 for screening, 0.86 for eligibility). Outcome-, statistic-
      and time-related MeSH were identified, and differences in allocation between
      groups were analyzed with chi-square and Fischer exact statistics. RESULTS: The
      most frequently allocated MeSH for included and active control articles were
      "dental restoration failure" (77% and 52%, respectively) and "treatment outcome"
      (54% and 48%, respectively). Outcome MeSH was similar between these groups (86%
      and 77%, respectively) and significantly greater than passive controls (10%, P <
      .001). Significantly more statistical MeSH were allocated to the included
      articles than to the active or passive controls (67%, 15%, and 1%, respectively,
      P < .001). Sixty-nine included articles specifically used Kaplan-Meier or life
      table analyses, but only 42% (n = 29) were indexed as such. Significantly more
      time-related MeSH were allocated to the included than the active controls (92%
      and 79%, respectively, P = .02), or to the passive controls (22%, P < .001).
      CONCLUSIONS: MeSH allocation within MEDLINE to time-to-event dental articles was
      inaccurate and inconsistent. Statistical MeSH were omitted from 30% of the
      included articles and incorrectly allocated to 15% of active controls. Such
      errors adversely impact search accuracy.

PMID- 24905263
TI  - Cytotoxicity of soft denture lining materials depending on their component types.
AB  - PURPOSE: To evaluate the difference in cytotoxicity of soft denture lining
      materials depending on their component types. MATERIALS AND METHODS: Ten
      commercially available soft denture lining materials (SDLM) consisting of five
      silicone-based materials and five acrylic-based materials were evaluated. For the
      MTT test, cured SDLM samples were extracted in a culture medium for 24 hours, and
      L-929 cells were incubated in the extracted medium for 24 hours. Cell viability
      was determined using a microplate reader and compared with those of the negative
      control, which were cultured in a culture medium without test material. Agar
      overlay test was performed for the cured SDLM samples according to International
      Organization for Standardization (ISO) 7405. RESULTS: Among silicone-based lining
      materials, GC Reline Soft, Mollosil plus, and Dentusil showed a cell viability of
      107.2% +/- 4.5%, 102.3% +/- 2.84%, and 93.0% +/- 8.0%, respectively, compared
      with the control. Mucopren and Sofreliner Tough displayed significantly lower
      cell viability (86.4% +/- 10.3% and 81.5% +/- 4.3%,respectively) compared with
      the control (P < .05). Among acrylic-based materials, Kooliner, Visco-gel, Soft
      liner, Dura Base, and Coe-Soft displayed cell viability of 99.2% +/- 14.6%, 93.1%
      +/- 9.5%, 89.1% +/- 9.8%, 87.6% +/- 7.9%, and 75.9% +/- 15.7%, respectively,
      compared with the control. Dura Base and Coe-Soft displayed significantly lower
      cell viability compared to the control. However, for all tested materials, cell
      viability exceeded the requirement limit of 70% specified in ISO 10993-5. In the
      agar overlay test, all five silicone-based materials and acrylic-based Kooliner
      were ranked as "noncytotoxic." However, Visco-gel was ranked as "mildly
      cytotoxic," and Soft liner, Coe-Soft, and Dura Base were ranked as "moderately
      cytotoxic." CONCLUSION: When an acrylic-based soft denture lining material is
      used, the possibility of a cytotoxic effect should be considered.

PMID- 24905265
TI  - Influence of the patient's clinical information on the diagnostic reproducibility
      and accuracy of MRI scans of temporomandibular joint pathologies.
AB  - PURPOSE: To evaluate the influence of the patient's clinical information on the
      accuracy as well as interexaminer and intraexaminer reproducibilities of
      temporomandibular joint (TMJ) magnetic resonance imaging (MRI) scans. MATERIALS
      AND METHODS: Forty MRI scans from 20 TMJs corresponding to 7 TMJ pathologies (ie,
      degenerative alterations of the condyle, degenerative alterations of the
      mandibular fossa, alterations in the morphology of the TMJ disc, disc
      displacement with reduction, disc displacement without reduction, TMJ effusion,
      and TMJ hypermobility) were assessed by seven uncalibrated specialists in
      temporomandibular disorders (TMD) at baseline, 30 day-, and 60-day follow-ups for
      accuracy and reproducibility. No clinical information was provided before the 60
      day follow up. RESULTS: Examiners had a poor to regular accuracy (0.10 to 0.36),
      kappa index and 5% to 60% correct positive diagnosis) when compared with the
      radiologist's diagnoses (gold standard). The interexaminer reproducibility ranged
      from moderate to substantial (kappa = 0.32 to 0.71), and the intraexaminer
      reproducibility ranged from moderate to perfect (kappa = 0.38 to 1.00). Provision
      of clinical information improved neither the accuracy nor the reproducibility of
      the results (P < .05), with the exception of the intraexaminer reproducibility of
      one examiner. CONCLUSIONS: Calibration is needed in assessing TMJ MRI scans, even
      when trained specialists are provided with clinical information from the patient.

PMID- 24905266
TI  - Mortality patterns in partially edentulous and edentulous elderly patients
      treated with dental implants.
AB  - An association between oral health, number of teeth, and mortality has been
      reported in the literature, but limited knowledge is available on mortality in
      elderly partially edentulous and edentulous patients treated with implants.
      PURPOSE: The aim of this retrospective study was to compare the mortality pattern
      in elderly patients (80 years or older) who were provided with implants and were
      partially or completely edentulous. MATERIALS AND METHODS: Between 1986 and 2003,
      a total of 266 elderly patients with a mean age of 83.0 years at the time of
      implant placement were included. The patients were provided with 1,384 Branemark
      System implants (Nobel Biocare) in 285 arches. The sample was divided into two
      subgroups: 108 edentulous patients and 158 partially edentulous patients.
      Information was collected for each individual regarding expected remaining
      lifetime at the time of implant surgery. Cumulative survival rate (CSR) was
      calculated and compared for the two subgroups covering 10 years and was also
      compared to expected CSR data for normal populations of comparable distribution.
      RESULTS: Mortality was significantly decreased (P < .05) for partially edentulous
      compared with edentulous patients (-10.4%) after 10 years of follow-up. CSR for
      the elderly groups showed a significant decrease in mortality compared with
      comparable groups of normal populations (P < .05). There was no significant
      difference in morality between healthy/nonhealthy patients at first surgery or
      patients with reported/unreported implant failures (P > .05). CONCLUSIONS:
      Elderly partially edentulous patients had significantly lower mortality compared
      with edentulous patients over a 10-year period of follow-up. Both subgroups also
      showed significantly lower mortality compared with normal populations of
      comparable sex and age at the time of implant surgery. The observation is
      interpreted as that these patients are healthier and more motivated to replace
      their lost teeth with implants than the normal population rather than that
      implant treatment per se reduces mortality.

PMID- 24905267
TI  - Agenesis of maxillary lateral incisor and tooth replacement: cost-effectiveness
      of different treatment alternatives.
AB  - PURPOSE: To evaluate the long-term cost-effectiveness of five treatment
      alternatives for maxillary lateral incisor agenesis where space maintenance and
      tooth replacement are indicated. MATERIALS AND METHODS: The following treatment
      modalities were considered: single-tooth implant-supported crown, resin-bonded
      fixed partial denture (FPD), cantilever FPD, full-coverage FPD, and
      autotransplantation. The cost-effectiveness for each treatment modality was
      determined as the ratio of the outcome of each modality divided by the cost.
      Direct costs, clinical and laboratory, were calculated based on national fee
      schedules and converted to international dollars using purchasing power parity
      exchange rates. Outcomes were based on the most recently published long-term (10
      year) survival rates. Sensitivity analyses were carried out, testing the
      robustness of the cost-effectiveness analysis. RESULTS: The five treatment
      modalities ranked in the following order from most to least cost-effective:
      autotransplantation, cantilever FPDs, resin-bonded FPDs, single-tooth implants
      and implant-supported crowns, and full-coverage FPDs. Sensitivity analysis
      illustrated that the cost-effectiveness analysis was reliable in identifying
      autotransplantation as the most and full-coverage FPDs as the least cost
      effective treatment modalities. CONCLUSIONS: When replacing a missing maxillary
      lateral incisor, the most costeffective, long-term treatment modality is
      autotransplantation, whereas the least cost-effective is full-coverage FPDs.
      However, factors such as patient age, the state of the dentition, occlusion, and
      tooth conservation should also influence the choice of restoration.

PMID- 24905268
TI  - Fracture resistance of a selection of full-contour all-ceramic crowns: an in
      vitro study.
AB  - This study aimed to evaluate the fracture resistance of monolithic single crowns
      made from zirconia (ZI), lithium disilicate (LS2), or feldspar ceramic (FC). Five
      groups of crowns representing a maxillary first molar were made with the
      appropriate dimensions according to the manufacturer's instructions. The ZI and
      LS2 crowns were luted adhesively or cemented conventionally on a metal abutment
      tooth analog. The feldspar ceramic crowns were luted adhesively. All specimens
      underwent axial loading until fracture. The crowns in the ZI groups possessed the
      highest fracture resistance independent of the mode of fixation.

PMID- 24905269
TI  - Zirconia-composite bonding after plasma of argon treatment.
AB  - PURPOSE: To compare the shear bond strength (SBS) values of resin cement to
      zirconia treated with a new activating method. MATERIALS AND METHODS: Forty-five
      zirconia specimens were divided into three groups: no treatment (group 1), plasma
      of argon cleaning for 375 seconds (group 2), and plasma of argon cleaning for 750
      seconds (group 3). Composite cylinders were bonded with a self-adhesive cement.
      After 40 days of water storage, specimens were subjected to the SBS test. Data
      were analyzed with one-way analysis of variance and the Neuman-Keuls multiple
      comparison test. RESULTS: Test groups obtained SBS values significantly higher
      (101% for group 2 and 81% for group 3) than controls. CONCLUSION: Plasma of argon
      appeared to improve bonding between zirconia and resin cement.

PMID- 24905271
TI  - Accidental ingestion of an untethered instrument during implant surgery.
AB  - During dental treatment, patients can swallow or inhale a foreign object as a
      result of several patient- and clinician-related factors; however, several
      methods can be used to prevent this complication. A 65-year-old man was referred
      to the Oral Implantology Clinic at the University of Amsterdam (ACTA) for a fixed
      prosthesis in the maxilla. While placing the implants, the screwdriver
      accidentally slipped from the fingers of the surgeon and was ingested by the
      patient. Since the difference between swallowing and inhaling cannot be
      accurately diagnosed, patient follow-up is advisable. 

PMID- 24905270
TI  - Bone mineral density and mandibular residual ridge resorption.
AB  - PURPOSE: This prospective, cross-sectional study evaluated the relationship
      between bone mineral density (BMD) and the width and height parameters of the
      mandibular residual ridge. MATERIALS AND METHODS: BMD was determined in the
      lumbar spine and femoral necks by dual energy x-ray absorptiometry (DXA) in 45
      edentulous, postmenopausal women (mean age, 72.08 +/- 8.53 years) who had used
      conventional complete dentures for at least 3 years. Measurements of the
      mandibular residual ridge were performed using cone beam computed tomography
      (CBCT). Height and width measurements were performed in the midline and adjacent
      to the mental foramina. Data were analyzed with descriptive and analytic
      statistics. The relationship between BMD and mandibular height and width
      measurements was assessed using analysis of variance as well as linear and
      multivariate regression analyses. Eight patients were excluded from the study
      because they did not complete both of the required imaging analyses (DXA and/or
      CBCT). RESULTS: There was no statistically significant relationship between BMD
      and mandibular bone height measurements in the midline and both regions of the
      mental foramina, and no statistically significant relationship existed between
      BMD and mandibular bone width measurements in the midline and both of the mental
      foramina regions. CONCLUSIONS: Postmenopausal women with reduced general BMD do
      not appear to have a reduction in the size of the mandibular residual ridge.

PMID- 24905272
TI  - Intraoral-extraoral combination prosthesis: improving retention using
      interconnecting magnets.
AB  - Osseointegrated implants have been well documented for retaining an obturator
      prosthesis as well as a facial prosthesis. However, when the defect extends to
      both the facial area and the maxilla, it is difficult to rehabilitate those
      defects to the satisfaction of the patient, especially in cases where implants
      cannot be placed on both sites. This case report describes the use of magnets to
      connect two prostheses, thereby increasing retention and patient comfort. 

PMID- 24905273
TI  - Eye movements during saccadic and fixation tasks in patients with homonymous
      hemianopia.
AB  - BACKGROUND: The aim of our study was to quantify ocular motor performance in
      patients with homonymous hemianopia and in healthy controls during saccadic and
      fixation tasks and to detect potential spontaneous adaptive mechanisms in the
      hemianopic patients. METHODS: Eye movements were recorded in 33 hemianopic
      patients (15 right, 18 left; disease duration, 0.2-29 years) and 14 healthy
      subjects by scanning laser ophthalmoscope allowing determination of the absolute
      fovea position relative to the stimulus without calibration. Landing accuracy of
      saccades was determined for 5 degrees  saccades, indicated by the number of
      dysmetric saccades (DS), and fixation stability (FS) after landing. In addition,
      during continuous fixation of a central cross, FS, and distribution of fixational
      eye movements (FEMs) were measured. Size of macular sparing was determined using
      custom microperimetry software (stimulus grid, 0.5 degrees ). RESULTS: Compared
      with controls, landing accuracy was decreased in hemianopic patients, indicated
      by significantly more DS (hypometric and hypermetric) to the blind side compared
      with the seeing side. The number of DS was greater in patients with macular
      sparing of <4 degrees . DS were not correlated with age and disease duration. FS
      after landing was lower after saccades to the blind side. Distribution of FEM
      during continuous fixation was asymmetrically shifted to the blind side,
      especially in cases of macular sparing of <4 degrees . CONCLUSIONS: Number of DS
      was not correlated with disease duration indicating insufficient spontaneous long
      term adaptation. Increased number of DS and decreased FS after landing in
      patients with small or absent macular sparing stresses the importance of intact
      parafoveal vision. Asymmetric FEMs during continuous fixation indicate an
      advantageous adaptive mechanism to shift the visual field border towards the
      hemianopic side.

PMID- 24905274
TI  - Vasospastic transient monocular visual loss: effect of treatment with different
      doses of nifedipine.
AB  - Transient monocular visual loss (TMVL) usually is due to hypoperfusion of the
      optic nerve or retinal circulation. After the exclusion of thromboembolic and
      carotid artery diseases, retinal vasospasm should be considered as an underlying
      cause of TMVL. We report a patient with an increasing number of transient attacks
      of unilateral blindness. Vasospasm was confirmed as the etiology by fundus
      photography during an attack. Nifedipine 10 mg/d decreased the severity of the
      visual loss and the number of attacks. The patient was relieved of symptoms
      entirely with a nifedipine dose of 20 mg/d.

PMID- 24905275
TI  - Optic neuritis in the setting of NMDA receptor encephalitis.

PMID- 24905276
TI  - Annual meeting of the North American neuro-ophthalmology society, Puerto Rico,
      March 1-6, 2014.

PMID- 24905277
TI  - Innervation pattern of polycystic ovaries in the women.
AB  - The aim of the present study was to determine the changes in both the
      distribution pattern and density of nerve fibers containing dopamine beta
      hydroxylase (DbetaH), vesicular acetylcholine transporter (VAChT), neuronal
      nitric oxide synthase (nNOS), substance P (SP), calcitonin gene related peptide
      (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin
      (SOM), galanin (GAL) and pituitary adenylate cyclase-activating polypeptide
      (PACAP) in the human polycystic ovaries. In the polycystic ovaries, when compared
      to the immunoreactions pattern observed in the control gonads, following changes
      were revealed: (1) an increase in the number of DbetaH-, VAChT-, VIP- or GAL
      immunoreactive (IR) nerve fibers within the stroma as well as in the number of
      DbetaH-IR fibers near primordial follicles and medullar veins and venules; (2) a
      reduction in the number of nerve fibers containing nNOS, CGRP, SOM, PACAP within
      the stroma and in the numbers of CGRP-IR fibers around arteries; (3) an
      appearance of SP- and GAL-IR fibers around medullar and cortical arteries,
      arterioles, veins and venules, with except of GAL-IR fibers supplying medullar
      veins; and (4) the lack of nNOS-IR nerve fibers near primordial follicles and VIP
      IR nerves around medullar arteries and arterioles. In conclusion, our results
      suggest that the changes in the innervation pattern of the polycystic ovaries in
      human may play an important role in the pathogenesis and/or course of this
      disorder. 

PMID- 24905278
TI  - Association of adiponectin with serum preheparin lipoprotein lipase mass in women
      independent of fat mass and distribution, insulin resistance, and inflammation.
AB  - Abstract Background: Substantially increased lipoprotein lipase (LPL) activity
      was reported in mice overexpressing adiponectin. METHODS: Associations of serum
      adiponectin with serum preheparin LPL mass (serum LPL), fat mass, and fat
      distribution and markers of insulin resistance and inflammation were examined in
      311 young and 148 middle-aged women. RESULTS: In young women, serum adiponectin
      was positively associated with high-density lipoprotein cholesterol (HDL-C) and
      serum LPL and inversely with body mass index (BMI), abdominal girth, trunk fat
      mass, trunk/lower-body fat ratio, serum leptin, and log high-sensitivity C
      reactive protein. These associations were confirmed in middle-aged women.
      Adiponectin showed positive association with the Matsuda insulin sensitivity
      index and inverse associations with homeostasis model assessment of insulin
      resistance, serum triglycerides, leukocyte count, interleukin-6, and plasminogen
      activator inhibitor-1 in middle-aged women but not in young women. Multivariate
      analysis revealed that serum LPL and trunk/lower-body fat ratio were significant
      determinants of adiponectin, not only in young women but also in middle-aged
      women. These associations were independent of markers of inflammation and insulin
      sensitivity/resistance. CONCLUSIONS: LPL mass in preheparin serum was associated
      with adiponectin levels independently of fat mass and distribution, systemic
      inflammation, and insulin resistance in healthy women. Therefore, LPL may
      represent a link between low adiponectin and dyslipidemia found in metabolic
      syndrome and type 2 diabetes mellitus.

PMID- 24905279
TI  - Tungsten sulfide enhancing solar-driven hydrogen production from silicon
      nanowires.
AB  - Tungsten sulfides, including WS2 (crystalline) and WS3 (amorphous), were
      introduced to silicon nanowires, and both can promote the photoelectrochemical
      hydrogen production of silicon nanowires. In addition, more enhancement of energy
      conversion efficiency can be achieved by the loading of WS3, in comparison with
      loading of WS2. Polarization curves of WS3 and WS2 suggest that WS3 has higher
      catalytic activity in the hydrogen evolution reaction than WS2, affording higher
      energy conversion efficiency in silicon nanowires decorated with WS3. The higher
      electrocatalytic activity of WS3 correlates with the amorphous structure of WS3
      and larger surface area of WS3, which result in more active sites in comparison
      with crystalline WS2. 

PMID- 24905280
TI  - Widespread hyperalgesia in adolescents with symptoms of irritable bowel syndrome:
      results from a large population-based study.
AB  - Widespread hyperalgesia is well documented among adult patients with irritable
      bowel syndrome (IBS), but little is known about pain sensitivity among
      adolescents with IBS. We examined pain sensitivity in 961 adolescents from the
      general population (mean age 16.1 years), including pain threshold and tolerance
      measurements of heat (forearm) and pressure pain (fingernail and shoulder) and
      cold pressor tolerance (hand). Adolescents with IBS symptoms (Rome III criteria)
      had lower heat pain thresholds compared to controls after adjustments for sex,
      comorbid pain, and psychological distress (mean difference = -.8  degrees C; 95%
      confidence interval [CI] = -1.6 to -.04). Similar results were found for pressure
      pain threshold at the shoulder (mean difference = -46 kPa; 95% CI = -78 to -13)
      and fingernail (mean difference = -62 kPa; 95% CI = -109 to -15), and for an
      aggregate of all 3 threshold measures (z-score difference = -.4; 95% CI = -.6 to 
      .2), though pressure pain threshold differences were nonsignificant after the
      final adjustments for psychological distress. No difference of pain tolerance was
      found between the IBS cases and controls. Our results indicate that adolescents
      in the general population with IBS symptoms, like adults, have widespread
      hyperalgesia. PERSPECTIVE: This is the first report of widespread hyperalgesia
      among adolescents with IBS symptoms in the general population, with lower pain
      thresholds found to be independent of sex and comorbid pain. Our results suggest
      that central pain sensitization mechanisms in IBS may contribute to triggering
      and maintaining chronic pain symptoms.

PMID- 24905281
TI  - Phosphatidylinositol 5-phosphate regulates invasion through binding and
      activation of Tiam1.
AB  - PtdIns5P is a lipid messenger acting as a stress-response mediator in the
      nucleus, and known to maintain cell activation through traffic alterations upon
      bacterial infection. Here, we show that PtdIns5P regulates actin dynamics and
      invasion via recruitment and activation of the exchange factor Tiam1 and Rac1.
      Restricted Rac1 activation results from the binding of Tiam1 DH-PH domains to
      PtdIns5P. Using an assay that mimics Rac1 membrane anchoring by using Rac1-His
      and liposomes containing Ni(2+)-NTA modified lipids, we demonstrate that
      intrinsic Tiam1 DH-PH activity increases when Rac1 is anchored in a PtdIns5P
      enriched environment. This pathway appears to be general since it is valid in
      different pathophysiological models: receptor tyrosine kinase activation,
      bacterial phosphatase IpgD expression and the invasive NPM-ALK(+) lymphomas. The
      discovery that PtdIns5P could be a keystone of GTPases and cytoskeleton
      spatiotemporal regulation opens important research avenues towards unravelling
      new strategies counteracting cell invasion. 

PMID- 24905282
TI  - Spatiotemporal neural dynamics of moral judgment: a high-density ERP study.
AB  - Morality is a pervasive aspect of human nature across all cultures, and
      neuroscience investigations are necessary for identifying what computational
      mechanisms underpin moral cognition. The current study used high-density ERPs to
      examine how moral evaluations are mediated by automatic and controlled processes
      as well as how quickly information and causal-intentional representations can be
      extracted when viewing morally laden behavior. The study also explored the extent
      to which individual dispositions in affective and cognitive empathy as well as
      justice sensitivity influence the encoding of moral valence when healthy
      participants make moral judgments about prosocial (interpersonal assistance) and
      antisocial (interpersonal harm) actions. Moral judgment differences were
      reflected in differential amplitudes for components associated with cognitive
      appraisal (LPP) as well as early components associated with emotional salience
      (N1 and N2). Moreover, source estimation was performed to indicate potential
      neural generators. A posterior-to-anterior shift was observed, with current
      density peaks first in right inferior parietal cortex (at the temporoparietal
      junction), then later in medial prefrontal cortex. Cognitive empathy scores
      predicted behavioral ratings of blame as well as differential amplitudes in LPP
      and component activity at posterior sites. Overall, this study offers important
      insights into the temporal unfolding of moral evaluations, including when in time
      individual differences in empathy influence neural encoding of moral valence. 

PMID- 24905283
TI  - Predictors of language lateralization in temporal lobe epilepsy.
AB  - Among patients with epilepsy, atypical (rightward) language lateralization has
      been associated with left-handedness, a left seizure focus, an early age at
      seizure onset, and familial sinistrality, although these associations are not
      consistently observed. No study has examined all of these factors in relation to
      language lateralization in the same epilepsy sample, let alone in a sample
      comprised only of patients with temporal lobe epilepsy. Moreover, little
      consideration has been given in previous studies to how language lateralization
      might be influenced by the interplay between different factors, or how much
      unique variance in language lateralization is explained by each factor. The
      primary aim of this study was to examine the combined influences of handedness,
      side of seizure focus, age at seizure onset, and familial sinistrality on
      language lateralization in temporal lobe epilepsy patients. A secondary aim was
      to determine which factors uniquely contribute to the prediction of language
      lateralization. 162 patients with intractable temporal lobe epilepsy underwent
      functional MRI language mapping, from which language lateralization indexes were
      derived. Degree of handedness was measured via the Edinburgh Handedness
      Inventory. Main and 2-way interaction effects on language lateralization indexes
      were examined via linear regressions and Fisher exact tests. Significant effects
      were next examined in multiple regressions to identify unique predictors of
      language lateralization indexes. When examined in isolation in regressions, only
      left-handedness and a left seizure focus predicted atypical (rightward) language
      lateralization. These results, however, were qualified by interaction effects
      demonstrating that stronger left hand preference was associated with greater
      atypical language lateralization only among patients with a left seizure focus,
      an early or intermediate age at seizure onset, or no familial sinistrality. In
      follow-up multiple regressions, the interaction terms accounted for a significant
      amount of variance in language lateralization indexes above and beyond main
      effects. Additionally, side of seizure focus and its interaction with handedness
      uniquely predicted language lateralization indexes. Results indicate that degree
      of left-handedness is a marker of greater atypical (rightward) language
      lateralization in temporal lobe epilepsy but only in the context of seizure
      characteristics that have the potential to drive joint reorganization of language
      and hand preference (i.e., left seizure focus, or early or intermediate age at
      seizure onset) or in the absence of a genetic predisposition for left-handedness
      (i.e., no familial sinistrality). This study advances existing knowledge by
      illustrating how different factors combine to jointly affect language
      lateralization, and by identifying side of seizure focus and its interaction with
      handedness as unique predictors of language lateralization in temporal lobe
      epilepsy. 

PMID- 24905284
TI  - Is the emotion recognition deficit associated with frontotemporal dementia caused
      by selective inattention to diagnostic facial features?
AB  - Frontotemporal dementia (FTD) is a debilitating neurodegenerative disorder
      characterized by severely impaired social and emotional behaviour, including
      emotion recognition deficits. Though fear recognition impairments seen in
      particular neurological and developmental disorders can be ameliorated by
      reallocating attention to critical facial features, the possibility that similar
      benefits can be conferred to patients with FTD has yet to be explored. In the
      current study, we examined the impact of presenting distinct regions of the face
      (whole face, eyes-only, and eyes-removed) on the ability to recognize expressions
      of anger, fear, disgust, and happiness in 24 patients with FTD and 24 healthy
      controls. A recognition deficit was demonstrated across emotions by patients with
      FTD relative to controls. Crucially, removal of diagnostic facial features
      resulted in an appropriate decline in performance for both groups; furthermore,
      patients with FTD demonstrated a lack of disproportionate improvement in emotion
      recognition accuracy as a result of isolating critical facial features relative
      to controls. Thus, unlike some neurological and developmental disorders featuring
      amygdala dysfunction, the emotion recognition deficit observed in FTD is not
      likely driven by selective inattention to critical facial features. Patients with
      FTD also mislabelled negative facial expressions as happy more often than
      controls, providing further evidence for abnormalities in the representation of
      positive affect in FTD. This work suggests that the emotional expression
      recognition deficit associated with FTD is unlikely to be rectified by adjusting
      selective attention to diagnostic features, as has proven useful in other select
      disorders. 

PMID- 24905285
TI  - Perceived animacy influences the processing of human-like surface features in the
      fusiform gyrus.
AB  - While decades of research have demonstrated that a region of the right fusiform
      gyrus (FG) responds selectively to faces, a second line of research suggests that
      the FG responds to a range of animacy cues, including biological motion and goal
      directed actions, even in the absence of faces or other human-like surface
      features. These findings raise the question of whether the FG is indeed sensitive
      to faces or to the more abstract category of animate agents. The current study
      uses fMRI to examine whether the FG responds to all faces in a category-specific
      way or whether the FG is especially sensitive to the faces of animate agents.
      Animate agents are defined here as intentional agents with the capacity for
      rational goal-directed actions. Specifically, we examine how the FG responds to
      an entity that looks like an animate agent but that lacks the capacity for goal
      directed rational action. Region-of-interest analyses reveal that the FG
      activates more strongly to the animate compared with the inanimate entity, even
      though the surface features of both animate and inanimate entities were
      identical. These results suggest that the FG does not respond to all faces in a
      category-specific way, and is instead especially sensitive to whether an entity
      is animate. 

PMID- 24905286
TI  - Functional correlates of the speech-in-noise perception impairment in dyslexia:
      an MRI study.
AB  - Dyslexia is a language-based neurodevelopmental disorder. It is characterized as
      a persistent deficit in reading and spelling. These difficulties have been shown
      to result from an underlying impairment of the phonological component of
      language, possibly also affecting speech perception. Although there is little
      evidence for such a deficit under optimal, quiet listening conditions, speech
      perception difficulties in adults with dyslexia are often reported under more
      challenging conditions, such as when speech is masked by noise. Previous studies
      have shown that these difficulties are more pronounced when the background noise
      is speech and when little spatial information is available to facilitate
      differentiation between target and background sound sources. In this study, we
      investigated the neuroimaging correlates of speech-in-speech perception in
      typical readers and participants with dyslexia, focusing on the effects of
      different listening configurations. Fourteen adults with dyslexia and 14 matched
      typical readers performed a subjective intelligibility rating test with single
      words presented against concurrent speech during functional magnetic resonance
      imaging (fMRI) scanning. Target words were always presented with a four-talker
      background in one of three listening configurations: Dichotic, Binaural or
      Monaural. The results showed that in the Monaural configuration, in which no
      spatial information was available and energetic masking was maximal,
      intelligibility was severely decreased in all participants, and this effect was
      particularly strong in participants with dyslexia. Functional imaging revealed
      that in this configuration, participants partially compensate for their poorer
      listening abilities by recruiting several areas in the cerebral networks engaged
      in speech perception. In the Binaural configuration, participants with dyslexia
      achieved the same performance level as typical readers, suggesting that they were
      able to use spatial information when available. This result was, however,
      associated with increased activation in the right superior temporal gyrus,
      suggesting the need to reallocate neural resources to overcome speech-in-speech
      difficulties. Taken together, these results provide further understanding of the
      speech-in-speech perception deficit observed in dyslexia. 

PMID- 24905287
TI  - Effect of temperature on symptom expression and sequence polymorphism of
      grapevine yellow speckle viroid 1 in grapevine.
AB  - Symptom expression of yellow speckle disease was studied in a row of 32
      individual Vitis vinifera cv. Chardonnay vines in the warmer summer of 2009/2010
      as compared with the cooler summer of 2011/2012 in South Australia. RT-PCR
      analysis showed that all these vines were positive for hop stunt viroid,
      grapevine yellow speckle viroid 1 (GYSVd-1) and grapevine rupestris stem pitting
      associated virus. Four vines named Vines 1, 8, 11 and 15 were selected for
      further analyses. Vines 1 and 8 had never shown yellow speckle (YS) symptoms,
      Vine 11 had always been symptomatic, and Vine 15 showed YS symptoms only in the
      summer of 2009/2010, but not in 2011/2012. Analysis of partial nucleotide (nt)
      sequence of GYSVd-1 from these vines showed two major sequence polymorphisms in
      the pathogenicity domain coinciding with the YS symptoms and the prevailing
      temperature in each season. One group designated UA group had a uridine (U) at
      position 309 and an adenine (A) at position 311, while another group designated
      AU group had the other way around: an "A" at position 309 and a "U" at position
      311. The AU group had never been reported before. The AU group was a minor
      variant in the GYSVd-1 population and not present in symptomatic Vine 11. In
      contrast, the UA group was dominant and present in all the vine samples.
      Surprisingly, all the asymptomatic vines, but not symptomatic vines, had the
      signature of the AU group. Whether the AU group is associated with the YS symptom
      expression is interesting. Our result provides a new insight into the sequence
      variability of viroid-inducing symptoms during two significantly different
      growing seasons. 

PMID- 24905288
TI  - TLR3 mediated innate immune response in mice brain following infection with
      Chikungunya virus.
AB  - Chikungunya virus (CHIKV) has received global attention due to the series of
      large-scale outbreaks in different parts of the world. Many unusual clinical
      severities including neurological complications and death were reported in recent
      outbreaks. The mechanism underlying the host immune response to CHIKV in the
      brain is poorly characterized. In this study, the neuropathogenesis of CHIKV with
      E1:A226V mutation was elucidated in 1 week old BALB/c mice. The virus was found
      to replicate in mice brain with peak titer of 10(4) on 6th day post infection.
      Immunohistochemical analysis revealed preferential virus localization in neuronal
      cells of cerebellum. The expression profiling of TLR, antiviral genes and
      cytokines in mice brain revealed significant up regulation of TLR3, TRAF-6, TICAM
      1, MCP-1, CXCL-10, IL-6, IL-4, ISG-15, MX-2, IFN-beta, OAS-3 genes that
      ultimately resulted in virus clearance from brain by day 9-10 suggesting
      activation of innate immune pathway. Further the effect of poly I: C
      (Polyinosinic: Polycytidylic acid), a TLR-3 agonist and potent IFN inducer on
      CHIKV neuropathogenesis was studied. Pretreatment of mice with Poly I: C caused
      reduction of CHIKV titer in brain and offered 100% protection of animals. The
      protection was mediated by an increased induction of TLR3, IFN-beta and antiviral
      genes in mice brain. Our result demonstrates that pre immune stimulation of
      animals by Poly I: C is effective inhibitor of CHIKV replication and might be a
      promising prevention agent against this virus. 

PMID- 24905289
TI  - First identification and quantification of lorcaserin in an herbal slimming
      dietary supplement.
AB  - The weight-loss drug lorcaserin, a FDA approved anorectic drug, was isolated from
      the dietary supplement "Lose quickly" claimed to be a pure natural fast slimming
      diet pill. After its purification by means of preparative liquid chromatography,
      its structure was characterized using LC-UV, NMR, MS, MS/MS, and IR spectroscopy.
      The amount of lorcaserin measured by qNMR was 6.6mg/capsule. 

PMID- 24905290
TI  - Binding of antioxidant flavone isovitexin to human serum albumin investigated by
      experimental and computational assays.
AB  - The flavonoids are a large class of polyphenolic compounds which occur naturally
      in plants where they are widely distributed. Isovitexin (ISO) is a glycosylated
      flavonoid that exhibits a potential antioxidant activity. Some recent studies
      have shown the pharmacokinetic activity of isovitexin in rat blood plasma,
      however, without detailing the molecular target that is linked and what
      physicochemical forces govern the interaction. In mammalians, the most abundant
      protein in blood plasma is the albumin and is not unlike with human, which human
      serum albumin (HSA) is the major extracellular protein and functions as a carrier
      of various drugs. The interaction between HSA and ISO was investigated using
      fluorescence, UV-vis absorbance, circular dichroism (CD), Fourier transform
      infrared spectroscopy (FT-IR) together with, computational methods like ab initio
      and molecular modeling calculation. Fluorescence quenching indicated that ISO
      location is within the hydrophobic pocket in subdomain IIA (site 1) of HSA, close
      to the Trp214 residue. The Stern-Volmer quenching constants determined at 288,
      298 and 308K and its dependence on temperature indicated that the quenching
      mechanism was static. From the analysis of binding equilibrium were determined;
      the binding site number and binding constants, with the correspondent
      thermodynamic parameters, DeltaH, DeltaG and DeltaS for HSA-ISO complex. Also, a
      second binding analysis, binding density function (BDF) method, which is
      independent of any binding model pre-established obtained similar results. The
      fluorescence resonance energy transfer estimated the distance between the donor
      (HSA-Trp214) and acceptor (ISO), while FT-IR and CD spectroscopy measured
      possible changes of secondary structure at the formation of the HSA-ISO complex.
      The optimized geometry of isovitexin calculation performed with its ground state
      by using DFT/B3LYP/6-311+G(d,p) method. The HSA-ISO complex interactions
      determined by molecular modeling tool corroborated with the thermodynamic
      analysis from the experimental data. 

PMID- 24905292
TI  - Evaluation of the photoprotective effect of beta-cyclodextrin on the emission of
      volatile degradation products of ranitidine.
AB  - The process of the photo-excitation of ranitidine hydrochloride (RAN) in a solid
      state makes visible changes to its colour and generates an unpleasant odour. The
      purpose of the present study was to observe the protective effects of beta
      cyclodextrin (CD) complexation as well as the effect of the mixture of two
      stoichiometries 1:1 and 1:2 (RAN:CD, IC) on the photostability of samples in a
      solid state. Samples of inclusion complexes (IC) and physical mixtures (PM) were
      prepared and irradiated for 48h in a Suntest CPS+ chamber. Irradiated samples
      were analyzed using nuclear magnetic resonance ((1)H NMR), infrared spectroscopy
      (FT-IR), the differential scanning calorimetry method (DSC) and thermogravimetry
      analysis (TGA). Volatiles were monitored with the use of headspace-solid phase
      microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The
      protective effect of CD was noticed with respect to IC, and also PM. Achieved
      photostabilization of complexed RAN against photodegradation could be explained
      due to either the inclusion of the furan part of RAN into the CD cavity as shown
      by the (1)H NMR ROESY (rotation frame nuclear Overhauser effect spectroscopy)
      spectrum or the screening effect of CD. FT-IR spectra, DSC curves and microscope
      images of irradiated samples of protected RAN did not indicate any physical
      changes, such as phase transfer. 

PMID- 24905291
TI  - Quantitative determination of telavancin in pregnant baboon plasma by solid-phase
      extraction and LC-ESI-MS.
AB  - The increasing incidence and severity of methicillin- and vancomycin-resistant
      infections during pregnancy prompted further development of telavancin. The
      understanding of the pharmacokinetics of telavancin during pregnancy is critical
      to optimize dosing. Due to ethical and safety concerns the study is conducted on
      the pregnant baboons. A method using solid-phase extraction coupled with liquid
      chromatography-single quadrupole mass spectrometry for the quantitative
      determination of telavancin in baboon plasma samples was developed and validated.
      Teicoplanin was used as an internal standard. Telavancin was extracted from
      baboon plasma samples by using Waters Oasis((r)) MAX 96-Well SPE plate and
      achieved extraction recovery was >66% with variation <12%. Telavancin was
      separated on Waters Symmetry C18 column with gradient elution. Two SIM channels
      were monitored at m/z 823 and m/z 586 to achieve quantification with simultaneous
      confirmation of telavancin identification in baboon plasma samples. The linearity
      was assessed in the range of 0.188MUg/mL to75.0MUg/mL, with a correlation
      coefficient of 0.998. The relative standard deviation of this method was <11% for
      within- and between-run assays, and the accuracy ranged between 96% and 114%. 

PMID- 24905293
TI  - Characterising African tick communities at a wild-domestic interface using
      repeated sampling protocols and models.
AB  - The sharing of habitat by wild and domestic animals may result in pathogen
      transmission, notably via ectoparasite vectors such as ticks. Interfaces between
      protected and communal lands constitute sharp transitions between areas occupied
      by host communities that are extremely contrasted in terms of composition,
      diversity and density. Empirical characterizations of tick communities and of
      their vertebrate hosts are strongly relevant for understanding the mechanisms
      leading to disease transmission between wild and domestic animals. In the present
      study we aimed at depicting the pattern of spatial variation in the density of
      immature ticks at such an interface located in Zimbabwe. At the end of the 2011
      rainy season, we applied a hierarchical repeated protocol to collect ticks. We
      used the drag-sampling method in the vegetation surrounding water pans used by
      ungulates in 3 distinct landscape compartments (i.e. national park, mixed
      compartment and communal lands) characterized by a differential use by wild and
      domestic hosts. We combined generalized linear mixed models with site occupancy
      models to (1) assess tick aggregation levels at different spatial scales, (2)
      identify and disentangle factors which influence the density and probability of
      tick detection, and (3) compare robust estimations of tick densities among the
      landscape compartments. Ticks belonging to the Amblyomma and Riphicephalus
      genuses were found to be the most abundant. At small scale, ticks were more often
      detected in the afternoon and were more abundant close to water pans for
      Amblyomma and Riphicephalus genuses. Riphicephalus spp. density was also higher
      in grassland and bushland vegetation types as compared to woodland vegetation
      type. At large scale, for the three detected genuses, density was much higher
      near water pans located in the communal lands as compared to the national park
      and mixed compartment. Given that host community's diversity is much lower in the
      communal areas than in the two other landscape compartments, these results are
      compatible with a dilution effect but not sufficient to demonstrate this effect
      without additional studies. Up to date, it is the first utilization of these
      rigorous sampling and statistical modelling methodologies to estimate tick
      density in African ecosystem simultaneously at large and small scales. 

PMID- 24905294
TI  - Histamine H1-receptor antagonists against Leishmania (L.) infantum: an in vitro
      and in vivo evaluation using phosphatidylserine-liposomes.
AB  - Considering the limited and toxic therapeutic arsenal available for visceral
      leishmaniasis (VL), the drug repositioning approach could represent a promising
      tool to the introduction of alternative therapies. Histamine H1-receptor
      antagonists are drugs belonging to different therapeutic classes, including
      antiallergics and anxyolitics. In this work, we described for the first time the
      activity of H1-antagonists against L. (L.) infantum and their potential
      effectiveness in an experimental hamster model. The evaluation against
      promastigotes demonstrated that chlorpheniramine, cinnarizine, hydroxyzine,
      ketotifen, loratadine, quetiapine and risperidone exerted a leishmanicidal effect
      against promastigotes, with IC50 values in the range of 13-84MUM. The
      antihistaminic drug cinnarizine demonstrated effectiveness against the
      intracellular amastigotes, with an IC50 value of 21MUM. The mammalian
      cytotoxicity was investigated in NCTC cells, resulting in IC50 values in the
      range of 57-229MUM. Cinnarizine was in vivo studied as a free formulation and
      entrapped into phosphatidylserine-liposomes. The free drug was administered for
      eight consecutive days at 50mg/kg by intraperitoneal route (i.p.) and at 100mg/kg
      by oral route to L. infantum-infected hamsters, but showed lack of effectiveness
      in both regimens, as detected by real time PCR. The liposomal formulation was
      administered by i.p. route at 3mg/kg for eight days and reduced the parasite
      burden to 54% in liver when compared to untreated group; no improvement was
      observed in the spleen of infected hamsters. Cinnarizine is the first
      antihistaminic drug with antileishmanial activity and could be used as scaffold
      for drug design studies for VL. 

PMID- 24905295
TI  - Trastuzumab-induced cardiomyopathy: incidence and associated risk factors in an
      inner-city population.
AB  - BACKGROUND: Although it is known that trastuzumab causes cardiotoxicity, its
      extent and reversibility are still in question. Earlier studies have not
      evaluated consecutive patients with reproducible nuclear ventriculography.
      OBJECTIVE: We sought to evaluate the baseline characteristics which predispose
      patients to increased risk of trastuzumab cardiotoxicity and to determine the
      natural history of the cardiotoxicity. METHODS AND RESULTS: Left ventricular
      ejection fraction (LVEF) was measured in 76 women aged 36-73 years who had been
      treated with trastuzumab at the University of Maryland Greenebaum Cancer Center.
      LVEF was determined at baseline and then 3, 6, 9, and 12 months after treatment
      initiation. Cardiotoxicity was defined as >= 16% decrease in LVEF or >= 10%
      decrease in LVEF to <50%. There were no differences in comorbidities, earlier
      treatment, or demographics between patients with and without trastuzumab-induced
      cardiomyopathy except that African Americans were more likely to develop
      decreased LVEF (P < .05). Twenty-one patients (28%) met criteria for
      cardiotoxicity. Four of those patients were continued on trastuzumab and 17
      patients had therapy withheld at some point. Only 1 patient developed symptomatic
      heart failure requiring inpatient hospitalization. LVEF improved in most patients
      regardless of whether or not trastuzumab was continued. CONCLUSIONS: Decreased
      LVEF while undergoing trastuzumab therapy occurs frequently and is usually
      reversible. African Americans had a higher risk of developing decreased LVEF.
      These findings raise clinically important questions as to whether it is necessary
      to discontinue trastuzumab for asymptomatic decrease in LVEF and whether African
      Americans are more predisposed to a decrease in LVEF while receiving trastuzumab.
      Further studies carefully assessing LVEF should address these hypotheses.

PMID- 24905296
TI  - Effects of spironolactone treatment in elderly women with heart failure and
      preserved left ventricular ejection fraction.
AB  - BACKGROUND: Although spironolactone has been shown to decrease morbidity and
      mortality in patients with heart failure and reduced left ventricular ejection
      fraction, its role in patients with heart failure and preserved left ventricular
      ejection fraction (HFpEF) is not well defined. In this study we investigated the
      mechanisms involved when elderly women with HFpEF are treated with
      spironolactone. METHODS AND RESULTS: Forty-eight women with HFpEF were enrolled
      in a randomized placebo-controlled trial and were assigned to 25 mg
      spironolactone daily (n = 24) or placebo (n = 24) for 6 months. Six-minute walk
      distance, clinical composite score, Doppler echocardiography, and biomarkers were
      determined at baseline and after 3 and 6 months of therapy. Six months of
      spironolactone treatment stabilized clinical symptoms, as demonstrated by
      significant worsening of the clinical composite score in the placebo group (P =
      .02). In addition, spironolactone treatment improved diastolic function by
      significantly increasing early diastolic tissue Doppler velocity of the lateral
      mitral annulus (lateral e'; P = .003) and significantly reducing the mitral peak
      E velocity to lateral e' ratio (lateral E/e'; P = .0001). Finally, spironolactone
      favorably affected remodeling through a reduction in myocardial fibrosis measured
      by a reduction in type III procollagen levels (P = .035). Six-minute walk
      distance did not significantly improve with spironolactone treatment compared
      with placebo. CONCLUSIONS: Spironolactone stabilizes functional capacity and
      symptoms and improves diastolic function, possibly through its ability to
      suppress type III procollagen synthesis.

PMID- 24905297
TI  - An experimental cell-based model for studying the cell biology and molecular
      pharmacology of 5-lipoxygenase-activating protein in leukotriene biosynthesis.
AB  - BACKGROUND: Subcellular distribution of 5-lipoxygenase (5-LO) to the perinuclear
      region and interaction with the 5-LO-activating protein (FLAP) are assumed as key
      steps in leukotriene biosynthesis and are prone to FLAP antagonists. METHODS:
      FLAP and/or 5-LO were stably expressed in HEK293 cells, 5-LO products were
      analyzed by HPLC, and 5-LO and FLAP subcellular localization was visualized by
      immunofluorescence microscopy. RESULTS: 5-LO and FLAP were stably expressed in
      HEK293 cells, and upon Ca(2+)-ionophore A23187 stimulation exogenous AA was
      efficiently transformed into the 5-LO products 5-hydro(pero)xyeicosatetraenoic
      acid (5-H(p)ETE) and the trans-isomers of LTB4. A23187 stimulation caused 5-LO
      accumulation at the nuclear membrane only when FLAP was co-expressed.
      Unexpectedly, A23187 stimulation of HEK cells expressing 5-LO and FLAP without
      exogenous AA failed in 5-LO product synthesis. HEK cells liberated AA in response
      to A23187, and transfected HEK cells expressing 12-LO generated 12-HETE after
      A23187 challenge from endogenous AA. FLAP co-expression increased 5-LO product
      formation in A23187-stimulated cells at low AA concentrations. Only in cells
      expressing FLAP and 5-LO, the FLAP antagonist MK886 blocked FLAP-mediated
      increase in 5-LO product formation, and prevented 5-LO nuclear membrane
      translocation and co-localization with FLAP. CONCLUSION: The cellular
      biosynthesis of 5-LO products from endogenously derived substrate requires not
      only functional 5-LO/FLAP co-localization but also additional prerequisites which
      are dispensable when exogenous AA is supplied; identification of these
      determinants is challenging. GENERAL SIGNIFICANCE: We present a cell model to
      study the role of FLAP as 5-LO interacting protein in LT biosynthesis in intact
      cells and for characterization of putative FLAP antagonists.

PMID- 24905298
TI  - Diabetes, oxidative stress and therapeutic strategies.
AB  - BACKGROUND: Diabetes has emerged as a major threat to health worldwide. SCOPE OF
      REVIEW: The exact mechanisms underlying the disease are unknown; however, there
      is growing evidence that excess generation of reactive oxygen species (ROS),
      largely due to hyperglycemia, causes oxidative stress in a variety of tissues.
      Oxidative stress results from either an increase in free radical production, or a
      decrease in endogenous antioxidant defenses, or both. ROS and reactive nitrogen
      species (RNS) are products of cellular metabolism and are well recognized for
      their dual role as both deleterious and beneficial species. In type 2 diabetic
      patients, oxidative stress is closely associated with chronic inflammation.
      Multiple signaling pathways contribute to the adverse effects of glucotoxicity on
      cellular functions. There are many endogenous factors (antioxidants, vitamins,
      antioxidant enzymes, metal ion chelators) that can serve as endogenous modulators
      of the production and action of ROS. Clinical trials that investigated the effect
      of antioxidant vitamins on the progression of diabetic complications gave
      negative or inconclusive results. This lack of efficacy might also result from
      the fact that they were administered at a time when irreversible alterations in
      the redox status are already under way. Another strategy to modulate oxidative
      stress is to exploit the pleiotropic properties of drugs directed primarily at
      other targets and thus acting as indirect antioxidants. MAJOR CONCLUSIONS: It
      appears important to develop new compounds that target key vascular ROS producing
      enzymes and mimic endogenous antioxidants. GENERAL SIGNIFICANCE: This strategy
      might prove clinically relevant in preventing the development and/or retarding
      the progression of diabetes associated with vascular diseases.

PMID- 24905299
TI  - Behavioral and biochemical evidences for antidepressant-like activity of
      palmatine in mice subjected to chronic unpredictable mild stress.
AB  - BACKGROUND: In the present study, antidepressant-like activity of palmatine was
      evaluated in unstressed and stressed young male Swiss albino mice. METHODS: The
      animals were subjected to unpredictable mild stress daily for 21 successive days
      to induce depression-like behavior. Palmatine (0.25, 0.5, 1 mg/kg, ip) was
      administered for 21 successive days to unstressed and stressed mice. The
      antidepressant-like activity was evaluated using the tail suspension test, forced
      swim test and sucrose preference test. RESULTS: Palmatine (0.5 and 1 mg/kg, ip)
      significantly decreased immobility periods of unstressed and stressed mice in the
      forced swim test and tail suspension test, thus indicating its significant
      antidepressant-like activity. Only the highest dose (1 mg/kg) of palmatine
      significantly reversed the stress-induced decrease in sucrose preference. There
      was no significant effect on locomotor activity of the mice by palmatine and
      fluoxetine. The antidepressant-like activity of palmatine was found to be
      comparable to fluoxetine (10 mg/kg) administered for successive 21 days.
      Palmatine (0.5 and 1 mg/kg, ip) significantly reversed the stress-induced
      increase in brain catalase levels, MAO-A activity, lipid peroxidation, plasma
      nitrite and corticosterone levels. CONCLUSIONS: Palmatine showed significant
      antidepressant-like activity in unstressed and stressed mice probably through
      inhibition of MAO-A activity, decrease in plasma nitrite levels and due to its
      antioxidant activity. In addition, palmatine also showed antidepressant-like
      activity in stressed mice probably through decrease in plasma corticosterone
      levels.

PMID- 24905300
TI  - The effect of intra-ventral hippocampus administration of TRPV1 agonist and
      antagonist on spatial learning and memory in male rats.
AB  - BACKGROUND: The role of transient receptor potential vanilloid 1 (TRPV1) in
      peripheral nervous system has been studied well but its role in the central
      nervous system remains to be studied in detail. The expression of TRPV1 receptors
      in hippocampus is suggesting that they may play an important role in higher
      cognitive functions such as learning and memory. METHODS: In the present study,
      the role of TRPV1 receptors in acquisition and retrieval of spatial memory of
      male Wistar rats was evaluated by intra-ventral hippocampus administration of
      TRPV1 selective agonist (OLDA) and antagonist (AMG9810) using Morris water maze.
      RESULTS: The results demonstrated that administration of either OLDA (0.001, 0.01
      and 0.1 MUg/rat) or AMG9810 (0.003, 0.03 and 0.3 MUg/rat) did not influence
      memory acquisition or retrieval. CONCLUSIONS: These data suggest that ventral
      hippocampal TRPV1 receptors possibly are not involved in spatial learning and
      memory.

PMID- 24905301
TI  - Possible involvement of nitric oxide mechanism in the neuroprotective effect of
      rutin against immobilization stress induced anxiety like behaviour, oxidative
      damage in mice.
AB  - Dietary supplements are widely used to manage stress and related consequences.
      However, the exact pathological mechanism and cellular cascades involved in the
      action of these supplements are not properly understood so far. Therefore, the
      present study has been designed to explore the neuroprotective mechanism of rutin
      against immobilization stress-induced anxiety-like behavioural and oxidative
      damage in mice. Laboratory Animal Centre A-strain (laca) mice were used in the
      present study. Rutin (20, 40, and 80 mg/kg), l-arginine (100 mg/kg), l
      nitroarginine methyl ester (l-NAME) (5 mg/kg) and vitamin-E (50 mg/kg) were
      administered for 5 days before 6h immobilization stress on 6th day. Various
      behavioural parameters (mirror chamber test, locomotor activity) followed by
      biochemical parameters (lipid peroxidation, nitrite concentration, reduced
      glutathione and catalase) in brain and then serum corticosterone level were
      assessed. 6 h immobilization stress produced anxiety-like behavioural in mirror
      chamber test, raised corticosterone level and oxidative stress (as evidenced by
      rise in lipid peroxidation, nitrite concentration, depletion of reduced
      glutathione and catalase activity) significantly as compared to naive group. 5
      days pre-treatment with rutin (40 and 80 mg/kg) causes a significant attenuation
      of locomotor activity, corticosterone level, oxidative stress as compared to
      control. Further, l-arginine (100 mg/kg) pre-treatment significantly reversed the
      protective effect of rutin (40 mg/kg) in 6 h immobilized animals. However, l-NAME
      (5 mg/kg) pre-treatment with rutin (40 mg/kg) potentiated their protective effect
      which was significant as compared to their effect per se. The present study
      suggests the involvement of nitric oxide mechanism in the neuroprotective effect
      of rutin against immobilization stress-induced anxiety-like behaviour and
      oxidative damage in mice.

PMID- 24905302
TI  - The influence of mianserin on TNF-alpha, IL-6 and IL-10 serum levels in rats
      under chronic mild stress.
AB  - BACKGROUND: Antidepressants are known to affect the immunological system through
      mechanisms which are not completely understood. The aim of the present study was
      to evaluate the effect of the atypical antidepressant mianserin on the levels of
      tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and interleukin-10
      (IL-10) in the blood of rats in an experimental model of depression. METHODS:
      Male Wistar rats were subjected to chronic mild stress (CMS) according to
      Willner's method for 6 weeks. Following the development of anhedonia, the
      stressed and control rats (non-stressed animals) were treated with mianserin (10
      mg/kg ip, twice daily) for three weeks. On the last day of the experiment, a
      lipopolysaccharide (LPS, 100 MUg/kg ip) was injected to mianserin- or vehicle
      treated rats. TNFalpha, IL-6 and IL-10 levels in the blood of the rats were
      assayed using ELISA methods. RESULTS: The results indicated a significantly
      increased TNFalpha level in stressed animals when compared with the non-stressed
      (control) group. The levels of IL-6 and IL-10 were also elevated, especially
      after LPS administration. Treatment with mianserin resulted in a significant
      lowering of TNFalpha and IL-6 levels both in LPS-treated and LPS-untreated
      animals. There was also a decrease in IL-10 concentration in LPS-treated stressed
      animals. CONCLUSIONS: The results confirm an increase in proinflammatory
      cytokines in the blood of rats with experimentally induced depression and show
      the protective role of the activity of mianserin on the cytokine levels,
      expressed in a lowering of TNFalpha and IL-6 levels in stressed animals, and of
      IL-10 levels after LPS administration.

PMID- 24905303
TI  - Drinking of flavored solutions by high preferring (WHP) and low preferring (WLP)
      alcohol-drinking rats.
AB  - BACKGROUND: Selective breeding alcohol-preferring (P) and alcohol-nonpreferring
      (NP) rats showed a strong preference for the sucrose solutions, whereas P rats
      intake greater amounts than NP rats. The aim of this study was the estimation of
      selectively bred ethanol-preferring (WHP - Warsaw High Preferring) and ethanol
      nonpreferring (WLP - Warsaw Low Preferring) rats for their preference for various
      tastes. METHODS: The oral drinking of the following substances was studied at a
      range of concentrations: sucrose (0.5-64.0 g/100 ml), NaCl (0.025-3.2 g/100 ml),
      citric acid (0.008-2.048 g/l), and sucrose octaacetate (0.002-0.512 g/l)
      solutions. Separate groups of 7-8 rats from each line were investigated of each
      of the four tastes. The investigated solutions were presented continuously
      keeping water and food always available. Concentrations of the various flavors
      were doubled every 48 h. RESULTS: Rats from WHP and WLP lines clearly revealed
      the preference for the sucrose solution and the highest preference was at the 4.0
      and 8.0 g/100ml sucrose concentration. Similar to sucrose, both lines exposed
      strong preference for the NaCl solution and this preference enhanced together
      with the increase of the NaCl concentration. Nevertheless their preference for
      the NaCl solutions decreased when the concentration of NaCl reached 1.600 g/100
      ml. Both lines of rats did not differ in citric acid or sucrose octaacetate
      intake at any of the concentrations studied. CONCLUSION: Selective breeding of
      rats (WHP) for high and rats (WLP) for low ethanol drinking is favorably
      correlated with the drinking of sweet and salty solutions and negatively
      correlated with the consumption of sour and bitter tastes.

PMID- 24905304
TI  - Imipramine and fluoxetine inhibit LPS-induced activation and affect morphology of
      microglial cells in the rat glial culture.
AB  - BACKGROUND: Recent evidence has suggested that antidepressants evoke
      neuroprotective and immunomodulatory effects in the brain, partly at least, by
      inhibiting glia activation. This study has been conducted on the
      lipopolysaccharide (LPS)-stimulated primary rat mixed glial cell culture in order
      to better recognize the influence of imipramine (a tricyclic antidepressant) and
      fluoxetine (a selective serotonin reuptake inhibitor) on the important balance
      between pro- and anti-inflammatory cytokines produced by the glial cells.
      Moreover, microscopic observations were made to describe the morphological
      alterations in the studied cell cultures exposed to the drugs. METHODS: The
      effect of both antidepressants on TNF-alpha, IL-1beta and IL-10 levels was
      determined by ELISA. The mRNA levels of mentioned cytokines were evaluated by qRT
      PCR assay. Moreover, drug influence on the LPS-stimulated level of NF-kappaB p65
      subunit in nuclear fraction was determined by the colorimetric transcription
      factor assay. RESULTS: After LPS-stimulation both drugs decreased concentration
      of TNF-alpha and IL-1beta in culture medium and expression of TNF-alpha and IL
      1beta mRNAs in cellular extracts. They also diminished the LPS-induced nuclear
      translocation of NF-kappaB p65 subunit. In contrast, imipramine and fluoxetine
      induced a few-fold weaker suppressing effect on the levels of IL-10. Parallelly
      to the inhibition of the LPS-induced inflammatory response, the antidepressants
      prevented the morphological alterations of cells elicited by LPS. Moreover, in
      unstimulated cultures imipramine but not fluoxetine caused transformation of
      microglia cells into cells with neuron-like morphology. CONCLUSIONS: Imipramine
      and fluoxetine, by modulating glia activation, may exert anti-inflammatory
      effects in the CNS. It also seems that microglia cells are important target
      particularly for imipramine.

PMID- 24905305
TI  - Assessment of antioxidant supplementation on the neuropathic pain score and
      quality of life in diabetic neuropathy patients - a randomized controlled study.
AB  - BACKGROUND: Diabetes is a chronic disease characterized by elevated blood glucose
      levels. The appropriate goals in the management of diabetes include maintaining
      blood glucose levels as close to the normal range as possible, minimizing the
      adverse effects of free radicals by enhancing antioxidant defenses.
      Supplementation with appropriate vitamins may therefore be of value in the
      prevention and treatment of diabetes. METHODS: A total of 92 patients with
      diabetic neuropathy were enrolled in this randomized controlled study from the
      general medicine department of a tertiary care hospital. Patients were randomized
      into two groups viz., usual care (n = 46) and intervention group (n = 46). Usual
      care group patients received pregabalin with oral hypoglycemic agents. Patients
      in the intervention group received vitamin-E along with their regular medicines.
      Pain intensity and quality of life (QoL) of patients were assessed using
      Neuropathy Pain Score and RAND 36 questionnaire. Blood samples were analyzed for
      the levels of random blood sugar level and HbA(1c) at the baseline and on the
      12th week. RESULTS: Significant (p < 0.05) decrease in the random blood sugar
      level was observed in intervention group when compared with the usual care group
      and a significant (p < 0.01) reduction in total pain score, and a significant (p
      < 0.05) improvement in physical health after 12 week treatment of vitamin-E was
      observed. CONCLUSION: The study concluded that vitamin-E is a natural antioxidant
      and it is found to be effective in reducing pain score in diabetic neuropathy
      patients. The future studies may be directed towards extended duration of action.

PMID- 24905306
TI  - Menin regulates spinal glutamate-GABA balance through GAD65 contributing to
      neuropathic pain.
AB  - BACKGROUND: Our previous work found that tumor suppressor menin potentiates
      spinal synaptic plasticity in the context of peripheral nerve injury-induced
      neuropathic hypersensitivity, but the underlying molecular mechanisms are not
      clear. We hereby assessed the role of menin in regulating the spinal balance
      between glutamate and GABA and its contribution to the pathological condition of
      nerve injury-induced hypersensitivity. METHODS: In spared nerve injury induced
      C57BL/6 mice, mechanical withdrawal threshold was measured with von Frey
      filaments after intrathecal administration of small interfering RNA (siRNA) of
      MEN1 or/and subcutaneous histone deacetylase (HDAC) inhibitors to control the
      level of glutamic acid decarboxylase 65 (GAD65). Immunoblotting and high
      performance liquid chromatography were used to detect the level of protein
      expression and spinal glutamate and GABA, respectively. RESULTS: Genetic
      knockdown of spinal menin alleviated nerve injury evoked mechanical
      hypersensitivity, which was strongly associated with the alteration of the spinal
      level of GAD65 that resulted in an imbalance of glutamate/GABA ratio from the
      baseline ratio of 5.8 +/- 0.9 (*10(-4)) to the peak value of 58.6 +/- 11.8 (*10(
      4)) at the day 14 after SNI (p < 0.001), which was reversed by MEN1 siRNA to 14.7
      +/- 2.1 (*10(-4)) at the day 14 after nerve injury (p < 0.01). In further,
      selective inhibitors of HDACs considerably reversed the ratio of spinal glutamate
      and GABA, and also alleviated the mechanical withdrawal threshold markedly.
      CONCLUSION: Our findings provide mechanistic insight into the contribution of the
      upregulated spinal menin to peripheral nerve injury induced neuropathic
      hypersensitivity by regulating glutamate-GABA balance through deactivating GAD65.

PMID- 24905307
TI  - The effect of safranal, a constituent of Crocus sativus (saffron), on tracheal
      responsiveness, serum levels of cytokines, total NO and nitrite in sensitized
      guinea pigs.
AB  - BACKGROUND: The effect of safranal (one of the constituents of Crocus sativus) on
      ovalbumin (OVA) sensitized guinea pigs was examined. METHODS: One group of
      sensitized guinea pigs were given drinking water alone (group S), three groups
      drinking water containing three concentrations of safranal and one group contain
      dexamethasone (S + D). Tracheal responses (TR) of the animals to methacholine as
      effective concentration causing 50% of maximum response (EC(50) M), TR to 0.1%
      OVA, relative to contraction induced by 100 MUM methacholine, IL-4, IFN-gamma,
      total NO and nitrite levels in serum were measured. RESULTS: The TR to both
      methacholine and OVA, the level of total NO, nitrite and IL-4 significantly
      increased but IFN-gamma and IFN-gamma/IL-4 ratio was decreased in group S
      compared controls (p < 0.05 to p < 0.001). The TR to both methacholine and OVA in
      treated animals with dexamethasone and all concentrations of safranal were
      significantly decreased compared to S group (p < 0.01 to p < 0.001). The level of
      serum IL-4 in treated guinea pigs was significantly decreased but IFN-gamma and
      IFN-gamma/IL-4 ratio was increased compared to S group (p < 0.01 to p < 0.001).
      The levels of total NO and nitrite were significantly decreased in treated groups
      compared to sensitized group (p < 0.05 to p < 0.001). CONCLUSION: These results
      showed a preventive effect for safranal on tracheal responses and serum cytokine,
      total NO and nitrite levels as well as increased Th1/Th2 balance in sensitized
      guinea pigs.

PMID- 24905308
TI  - Renoprotective activity of aliskiren, a renin inhibitor in cyclosporine A induced
      hypertensive nephropathy in dTG mice.
AB  - BACKGROUND: Hypertensive nephropathy is moving up the charts to number 2 after
      diabetic nephropathy in terms of diagnostic frequency cited as causing end stage
      renal disease (ESRD). METHOD: Hypertensive nephropathy was produced in mildly
      hypertensive C57BL/6-(hREN)/(hAGT) double transgenic (dTG) mice with 20 mg/kg of
      cyclosporine A (CsA) administered subcutaneously (sc) daily for 28 days. CsA dose
      20 mg/kg was selected for the study as this dose offered significant alteration
      in blood pressure, biochemical parameters and moderate nephropathy in kidney.
      Effect of aliskiren oral treatment twice daily consequently for 28 days at 10
      mg/kg body weight was evaluated against CsA induced hypertensive nephropathy.
      Systolic blood pressure (SBP) was measured by non invasive tail cuff method.
      Kidney function test (blood urea nitrogen, serum creatinine, urea and uric acid)
      and kidney injury biomarker (tumor necrosis factor-alpha (TNF-alpha) and
      interlekin-6) level was assessed in serum, TNF-alpha, IL-6, transforming growth
      factor-beta1 (TGF-beta1) and kidney injury molecule-1 (KIM-1) was assayed in
      kidney homogenate. Urinary KIM-1 levels were assessed as an early biomarker of
      nephropathy. RESULT: Significant hypertensive nephropathy and increase in serum
      levels of biomarkers was observed in CsA treated animals when compared with
      Control group. Aliskiren treatment elicited significant renoprotection by
      preventing the increase in blood pressure and levels of serum biomarkers and also
      reduced the nephropathic alterations in the kidney histoarchitecture. CONCLUSION:
      A correlation between pharmacological, biochemical and histological findings has
      been established in mouse model. The present findings have indicated the
      renoprotective activity of aliskiren in CsA induced hypertensive nephropathy,
      which may be due to its antihypertensive, anti-inflammatory as well as anti
      apoptopic action.

PMID- 24905309
TI  - The effects of celiprolol on serum concentrations of proinflammatory cytokines in
      hypertensive (SHR) and normotensive (WKY) rats.
AB  - BACKGROUND: A growing body of evidence suggests that some cardiovascular drugs
      could modulate the level of proinflammatory cytokines. Therefore, the aim of the
      present study was to investigate whether celiprolol, a third generation beta
      adrenoceptor blocker, affects lipopolysaccharide (LPS)-induced serum
      concentrations of TNF-alpha, IL-1beta, IL-6 in normotensive (WKY) and
      spontaneously hypertensive (SHR) rats. METHODS: Celiprolol (150 mgkg(-1)) or
      vehicle was administered by gavage once daily for 21 days. Arterial blood
      pressure was measured in conscious rats, using the tail-cuff method. Serum
      concentrations of proinflammatory cytokines were measured with enzyme-linked
      immunosorbent assay kits. Additionally, plasma concentrations of total
      cholesterol, HDL-cholesterol and triglycerides were evaluated. RESULTS: In
      normotensive WKY rats celiprolol did not affect heart rate, blood pressure, or
      the serum concentrations of triglycerides, total cholesterol or HDL-cholesterol.
      In hypertensive animals the drug decreased lipid parameters, increased diastolic
      and mean blood pressure after the first week of administration, and produced a
      small but significant decrease in heart rate after the first two weeks of the
      treatment. In both groups of animals, celiprolol decreased LPS-stimulated serum
      concentration of IL-6 but did not affect levels of TNF-alpha and IL-1beta.
      CONCLUSIONS: It is suggested that the IL-6-modulating properties of celiprolol
      could provide additional value to the therapeutic effectiveness of the drug in
      the treatment of hypertension.

PMID- 24905310
TI  - Effect of calcium channel blockers on paraoxonase-1 (PON1) activity and oxidative
      stress.
AB  - BACKGROUND: In this study, we investigated the in vitro effects of calcium
      channel blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate)
      on the activity of paraoxonase-1 (PON1). METHODS: PON1 was purified from human
      serum using simple chromatographic methods, including DEAE-Sephadex anion
      exchange and Sephadex G-200 gel filtration chromatography. RESULTS: The calcium
      channel blockers decreased the in vitro PON1 activity. The inhibition mechanism
      of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and
      isradipine were competitive inhibitors. CONCLUSIONS: Our results showed that
      calcium channel blockers exhibit inhibitory effects on PON1 at low
      concentrations. The IC(50) values for nifedipine, nitrendipine, isradipine, and
      amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304
      mM, respectively, and the K(i) constants were calculated to be 0.222 +/- 0.049
      mM, 0.151 +/- 0.067 mM, 0.286 +/- 0.137 mM, and 0.321 +/- 0.002 mM, respectively.

PMID- 24905311
TI  - Effects of carnosine on prooxidant-antioxidant status in heart tissue, plasma and
      erythrocytes of rats with isoproterenol-induced myocardial infarction.
AB  - Rats were injected with isoproterenol (ISO; 110 mg/kg, ip, 2 doses, 24 h
      interval) to induce acute myocardial infarction (AMI) and were sacrificed 6 and
      24 h after the last ISO injection. The heart tissue, plasma and erythrocytes of
      these rats were evaluated for cardiac markers and oxidative stress parameters.
      Levels of cardiac troponin T (cTnT) and the activities of creatine kinase (CK),
      lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in plasma were
      increased 6 and 24 h after ISO treatment. The levels of malondialdehyde (MDA),
      diene conjugate (DC), and protein carbonyl (PC) were increased in heart tissue
      and plasma, while levels of erythrocyte MDA and glutathione (GSH) and plasma
      ferric reducing antioxidant power (FRAP) were also increased. However, GSH levels
      and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH
      Px) decreased in heart tissue of rats with AMI. We also investigated the effects
      of carnosine (CAR) treatment on these parameters 24 h after the last ISO
      injection. CAR (250 mg/kg/day; ip) treatments were carried out either 10 days
      before ISO injection or 2 days concomitant with ISO. Pretreatment with CAR
      decreased plasma LDH and AST activities and ameliorated cardiac histopathological
      changes in ISO-treated rats. Cardiac MDA, DC and PC levels decreased, but GSH
      levels and SOD and GSH-Px activities increased. However, the increases in plasma
      MDA and PC levels as well as erythrocyte H(2)O(2)-induced MDA and GSH levels did
      not change due to CAR pretreatment. In conclusion, our findings indicate that CAR
      pretreatment may have protective effects on ISO-induced cardiac toxicity by
      decreasing oxidative stress.

PMID- 24905312
TI  - The effect of lipoic acid on cyanate toxicity in the rat heart.
AB  - BACKGROUND: Cyanate is a uremic toxin formed principally via spontaneous urea
      biodegradation. Its active isoform, isocyanate, is capable of reaction with
      proteins by N and S carbamoylation, which influences their structure and
      function. Sulfurtransferases implicated in anaerobic cysteine transformation and
      cyanide detoxification belong to the enzymes possessing SH groups in their active
      centers. The present studies aimed to demonstrate the effect of cyanate and
      lipoic acid on the activity of these enzymes as well as on the level of
      antioxidants and prooxidants in the rat heart. METHODS: Wistar rats, which
      received intraperitoneal injections of cyanate and lipoic acid alone and in
      combination were sacrificed 2.5 h after the first injection. The hearts were
      isolated and homogenized in phosphate buffer and next biochemical assays were
      performed comprising determination of the level of glutathione, malondialdehyde
      and sulfane sulfur and the activity of antioxidant enzymes as well as glutathione
      S-transferase and gamma glutamyl transferase. RESULTS: Sulfurtransferases and
      glutathione S-transferase were deactivated by cyanate treatment. It was
      accompanied by the decreased level of glutathione and sulfane sulfur and the
      increased level of reactive oxygen species and malondialdehyde. In parallel,
      antioxidant enzymes: catalase, glutathione peroxidase and gamma glutamyl
      transferase were activated under such circumstances. Lipoic acid, administered in
      combination with cyanate prevented the decrease in the level of glutathione and
      reduction of a pool of sulfane sulfur-containing compounds, concomitantly
      preserving the activity of antioxidant enzymes. CONCLUSIONS: Since uremia,
      characterized by the elevated cyanate/isocyanate level, is accompanied by
      frequent cases of cardiovascular diseases, the addition of lipoic acid to the
      therapy seems promising in prophylaxis of heart diseases in uremic patients.

PMID- 24905314
TI  - Biological approach of anticancer activity of new benzimidazole derivatives.
AB  - BACKGROUND: A series of new benzimidazole derivatives, earlier synthesized, was
      tested in vitro as new bioreductive prodrugs with the potential anticancer
      activity. Their effect on the DNA destruction and growth inhibition into selected
      tumor cell lines at normoxia and hypoxia conditions was determined. METHODS: The
      human lung adenocarcinoma A549 cell line was used to determine the anticancer
      activity of the analyzed compounds by using WST-1 assay. The apoptosis test
      (caspase 3/7 assay) was used to define the cytotoxic way of tumor cells death.
      Additionally test In situ DNA Damage Assay Kit was applied to recognize the DNA
      destruction. RESULTS: Four of the examined compounds (1, 3, 7, 9) show a very
      good antiproliferative effect and three of them are specific for hypoxia
      conditions (2, 4, 8). CONCLUSION: Compound 8 is the most cytotoxic against human
      lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/normoxia cytotoxic
      coefficient of compound 8 (4.75) is close to hypoxia/normoxia cytotoxic
      coefficient of tirapazamine (5.59) - reference substance in our experiments and
      this parameter locates it between mitomycin C and 2-nitroimidazole
      (misonidazole). The screening test of the caspase-dependent apoptosis proved that
      the exposure of compounds 1-2 and 7-8 against A549 cells for a 48 h promote
      apoptotic cell death. Additionally, the test of the DNA damage established that
      compounds 1, 2, 7, 8 are specific agents for the hypoxia-selective cytotoxicity
      of nitrobenzimidazoles [6,26].

PMID- 24905313
TI  - Modifications of histamine receptor signaling affect bone mechanical properties
      in rats.
AB  - Histamine receptors are expressed on bone cells and histamine may be involved in
      regulation of bone metabolism. The aim of the present study was to investigate
      the effects of loratadine (an H(1) receptor antagonist), ranitidine (an H(2)
      receptor antagonist) and betahistine (an H(3) receptor antagonist and H(1)
      receptor agonist) on bone mechanical properties in rats. Loratadine (5 mg/kg/day,
      po), ranitidine (50 mg/kg/day, po), or betahistine dihydrochloride (5 mg/kg/day,
      po), were administered for 4 weeks to non-ovariectomized and bilaterally
      ovariectomized (estrogen-deficient) 3-month-old rats, and their effects were
      compared with appropriate controls. Serum levels of bone turnover markers, bone
      mineralization and mechanical properties of the proximal tibial metaphysis,
      femoral diaphysis and femoral neck were studied. In rats with normal estrogen
      level, administration of loratadine slightly favorably affected mechanical
      properties of compact bone, significantly increasing the strength of the femoral
      neck (p < 0.05), and tending to increase the strength of the femoral diaphysis.
      Ranitidine did not significantly affect the investigated parameters, and
      betahistine decreased the strength of the tibial metaphysis (cancellous bone, p <
      0.01). There were no significant effects of the drugs on serum bone turnover
      markers. In estrogen-deficient rats, the drugs did not significantly affect the
      investigated skeletal parameters. In conclusion, the effects of histamine H(1),
      H(2) and H(3) receptor antagonists on the skeletal system in rats were
      differential and dependent on estrogen status.

PMID- 24905315
TI  - The effects of selected inhibitors of histone modifying enzyme on C6 glioma
      cells.
AB  - BACKGROUND: Aberrant epigenetic histone modifications are implicated in cancer
      pathobiology, therefore histone modifying enzymes are emerging targets for anti
      cancer therapy. There is a few evidence for deregulation of the histone modifying
      enzymes in glioblastomas. Glioma treatment is a clinical challenge due to its
      resistance to current therapies. METHODS: The effect of selected inhibitors on
      epigenetic modifications and viability of glioma C6 cells were studied using
      immunofluorescence and MTT metabolism test. RESULTS: We found that VPA and TSA
      increase histone H4 acetylation in glioma cells, while chaetocin and BIX01294 at
      low concentrations reduce H3K9me3, and 3DZNep decreases H3K27me3. Long-term
      treatment with some epigenetic inhibitors affects viability of glioma cells.
      CONCLUSIONS: We established the concentrations of selected inhibitors which in C6
      glioma cells inhibit the enzyme activity, but do not decrease cell viability,
      hence allow to study the role of histone modifications in C6 glioma biology.

PMID- 24905317
TI  - Fluvastatin inhibits growth and alters the malignant phenotype of the C6 glioma
      cell line.
AB  - BACKGROUND: Fluvastatin is a member of the family of HMG-CoA reductase inhibitors
      (statins) extensively used in medical practice. Increasing evidence suggests that
      fluvastatin may be implicated in suppression of cancer growth and development.
      The aim of the present study was to investigate the anti-cancer potential of
      fluvastatin in C6 rat malignant glioma cells. METHODS: First, the effects of
      fluvastatin on cell viability (MTT assay), proliferation (BrdU assay), cell
      morphology, and cytoskeleton were examined. Subsequently, its effect on
      extracellular signal regulated kinase 1 and 2 (ERK1/2) and c-Jun N-terminal
      kinase 1 and 2 (JNK 1/2) expression was estimated by Western blot. Finally, the
      influence of fluvastatin on cell migration and production of MMP-9 and VEGF was
      determined using a wound-healing assay and ELISA test, respectively. RESULTS: The
      results obtained showed that fluvastatin had a remarkable inhibitory and
      cytotoxic effect on tumor C6 cells (IC(50) = 8.6 MUM, 48 h), but did not inhibit
      the growth of normal neuronal cells. The concentrations from 1 to 10 MUM induced
      marked morphologic alterations typical for apoptosis including shrinkage of
      cytoplasm, chromatin condensation, and nucleus breakdown. CONCLUSION: The
      inhibitory effects of fluvastatin on cell proliferation seemed to be associated
      with decreased p-ERK1/2 expression, upregulation of p-JNK1/2, and reduction in
      the MMP-9 and VEGF concentrations in culture media. The high anticancer
      (antiproliferative, proapoptotic, antiinvasive) activity of fluvastatin and lack
      of its toxicity against normal cells indicate a potential use of this statin in
      the treatment of malignant glioma.

PMID- 24905316
TI  - Antitumoral effect of a selective Rho-kinase inhibitor Y-27632 against Ehrlich
      ascites carcinoma in mice.
AB  - BACKGROUND: The Rho proteins and Rho-kinase (ROCK) enzymes are responsible for
      signal transduction, and cause cell permeability, contractility, differentiation,
      migration, proliferation or apoptosis depending on cell types. All of these
      functions are vital for cancer initiation and progression. In this study, the
      preventive and protective effects of a selective ROCK inhibitor Y-27632 against
      Ehrlich ascites carcinoma in Swiss albino mice were investigated. METHODS: Adult
      male albino mice were divided into five equal groups, and Y-27632 (0.1, 1, and 10
      mg/kg) was given to groups as two steps; before (pre-carcinoma) and after
      inoculation of carcinoma cell suspensions (post-carcinoma). At the end of the
      experiments (at day 15), cardiac blood samples, the ascitic fluid, and intestinal
      specimens were collected for histopathology and biochemical investigation.
      RESULTS: Significant decreases in the body weight and immunostaining scores in
      small and large intestine for ROCK2, preservation of serum glutathione (GSH)
      levels, and an increase in tumor level of nitric oxide were recorded in groups
      pretreated with Y-27632. However, treatment with Y-27632 after tumor inoculation
      did not affect body weight and ROCK2 immunostaining scores, increased serum MDA
      levels, and decreased GSH levels. CONCLUSIONS: This is the first study on the
      effectiveness of Y-27632 in this experimental tumor model. Our findings provided
      direct evidence for ROCK involvement in tumor development. These data suggest
      that pretreatment with Y-27632 has a protective effect against tumor formation.

PMID- 24905318
TI  - Kynurenic acid inhibits proliferation and migration of human glioblastoma T98G
      cells.
AB  - BACKGROUND: Kynurenic acid (KYNA), tryptophan metabolite synthesized in the
      kynurenine pathway, is an endogenous antagonist of alpha-7 nicotinic receptor and
      all ionotropic glutamate receptors: N-methyl-D-aspartate (NMDA) receptor, alpha
      amino-3-hydroxy-5-methyl-4-isoxasole propionate (AMPA) receptor and kainate
      receptor. The antiproliferative activity of KYNA toward colon and renal cancer
      cells has recently been discovered. The aim of the study was to verify whether
      human Glioblastoma tumors contain KYNA and if KYNA influences glioma cell
      proliferation and migration. METHODS: KYNA content in Glioblastoma tumor samples
      was determined using HPLC. Proliferation of human glioblastoma T98G cells was
      measured by means of MTT and BrdU assays. Wound assay was used to evaluate the
      effect of KYNA on cancer cell migration. RESULTS: KYNA was detected in all tested
      Glioblastoma tumor samples (100.3 +/- 17.6 pmol/g wet weight). In a series of
      experiments the antiproliferative activity of KYNA against T98G cells was
      revealed (IC(50) = 1.3 mM). Moreover, KYNA reversed the stimulatory effect of
      glutamate on glioma cell proliferation and enhanced antiproliferative effect of
      glutamate receptor antagonists MK801 and GYKI 52466. Next, KYNA at concentrations
      much lower than those needed to reduce cell proliferation elicited a prominent
      inhibitory effect on glioma cell motility. Moreover, co-incubation of
      temozolomide, a drug commonly used in antiglioblastoma therapy, with KYNA gave a
      superior effect than each of the substances applied alone. CONCLUSIONS: We
      demonstrate the antiproliferative and antimigrative potential of KYNA against
      glioma cells in vitro.

PMID- 24905319
TI  - Epicutaneous immunization with protein antigen TNP-Ig and NOD2 ligand muramyl
      dipeptide (MDP) reverses skin-induced suppression of contact hypersensitivity.
AB  - BACKGROUND: Epicutaneous (EC) immunization offers a new method of a needle-free
      and self-administrable immunization by using a topically applied patch to deliver
      vaccine. We have previously shown that EC immunization with hapten-conjugated
      protein antigen TNP-Ig prior to hapten sensitization inhibits Th1-mediated
      contact hypersensitivity (CHS) in mice. Our further work showed that EC
      immunization with TNP-Ig and Toll-like receptor (TLR) ligands prior to hapten
      sensitization reverses skin-induced suppression. METHODS: Animal model of contact
      hypersensitivity was used to study reversal of skin-induced suppression. RESULTS:
      Current work showed that EC immunization with protein antigen TNP-Ig and MDP NOD2
      agonist - muramyldipeptide (L isoform) reverses skin-induced suppression of CHS.
      On the other hand L18-MDP NOD2 agonist - muramyldipeptide with a C18 fatty acid
      chain and MDP control - negative control for MDP - muramyldipeptide (D isoform,
      inactive) did not reverse skin-induced suppression. "Transfer in" experiment
      showed that reversal of skin-induced suppression can be adoptively transferred
      with lymphoid cells isolated from donors EC treated with TNP-Ig and MDP NOD2
      agonist. Moreover, experiment employing two non-cross-reacting antigens TNP-Ig
      and OX-Ig proved that reversal of skin-induced suppression is antigen specific.
      Additionally, lymph node cells isolated from mice EC immunized with TNP-Ig and
      MDP NOD2 agonist produced increased level of IFN-gamma suggesting that this
      cytokine might be involved in reversal of skin-induced suppression. CONCLUSION:
      This work shows that EC immunization with protein antigen plus NOD2 ligand MDP
      may be a potential tool to increase the immunogenicity of weekly immunogenic
      antigens.

PMID- 24905320
TI  - The influence of the time of day on midazolam pharmacokinetics and
      pharmacodynamics in rabbits.
AB  - BACKGROUND: This study evaluates the time-of-day effect on midazolam and 1-OH
      midazolam pharmacokinetics, and on the sedative pharmacodynamic response in
      rabbits. Also, circadian fluctuations in rabbits' vital signs, such as the blood
      pressure, heart rate and body temperature were examined. The water intake was
      measured in order to confirm the presence of the animals' diurnal activity. The
      secondary aim involved the comparison of two methods of data analysis: a
      noncompartmental and a population modeling approach. METHODS: Twelve rabbits were
      sedated with intravenous midazolam 0.35 mg/kg at four local times: 09.00, 14.00,
      18.00 and 22.00 h. Each rabbit served as its own control by being given a single
      infusion at the four different times of the day on four separate occasions. The
      values of the monitored physiological parameters were recorded during the
      experiment and arterial blood samples were collected for midazolam assay. The
      pedal withdrawal reflex was used as the measurement of the sedation response. Two
      and one compartmental models were successfully used to describe midazolam and 1
      OH midazolam pharmacokinetics. The categorical pharmacodynamic data were
      described with a logistic model. RESULTS AND CONCLUSIONS: We did not find any
      time-of-day effects for the pharmacokinetic and pharmacodynamics parameters of
      midazolam. For 1-OH midazolam, statistically significant time-of-day differences
      in the apparent volume of distribution and clearance were noticed. They
      corresponded well with the rabbits' water intake. The noncompartmental and model
      based parameters were essentially similar. However, more information can be
      obtained from the population model and this method should be preferred in
      chronopharmacokinetic and chronopharmacodynamic studies.

PMID- 24905321
TI  - Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after
      intravenous administration in Chinese patients with pain.
AB  - OBJECTIVES: The aim of this study is to evaluate the pharmacokinetic profile of
      oxycodone and three of its metabolites, noroxycodone, oxymorphone and
      noroxymorphone after intravenous administration in Chinese patients with pain.
      METHODS: Forty-two subjects were assigned to receive intravenous administration
      of oxycodone hydrochloride of 2.5, 5 or 10 mg. Plasma and urine samples were
      collected for up to 24 h after intravenous administration of oxycodone
      hydrochloride. RESULTS: Pharmacokinetic parameters showed that mean values of
      C(max), AUC(0-t) and AUC(0-infinity) of oxycodone were dose dependent, whereas
      Tmax and t(1/2) were not. The mean AUC(0-t) ratio of noroxycodone to oxycodone
      ranged from 0.35 to 0.42 over three doses, and those of noroxymorphone, or
      oxymorphone, to oxycodone were ranging of 0.06-0.08 and 0.007-0.008,
      respectively. Oxycodone and its three metabolites were excreted from urine.
      Approximately 10% of unchanged oxycodone was recovered in 24 h. Most adverse
      events (AEs) reported were mild to moderate. The frequently occurred AEs were
      dizziness, nausea, vomiting, drowsiness and fatigue. No dose-related AEs were
      found. CONCLUSION: Our pharmacokinetics of oxycodone injection in Chinese
      patients with pain strongly support continued development of oxycodone as an
      effective analgesic drug in China.

PMID- 24905323
TI  - Combination therapy of gamma-aminobutyric acid derivative promotes proton pump
      inhibitor based healing of reflux esophagitis in animal model.
AB  - BACKGROUND: The present study was undertaken to elucidate the effect of
      omeprazole and baclofen on experimental esophagitis in albino rats. METHODS:
      Groups of rats, fasted overnight received normal saline (3 ml/kg, ip; sham
      control) or toxic control (3 ml/kg, ip) or omeprazole (30 mg/kg, ip) or baclofen
      (20 mg/kg, ip) or their combinations, were subjected to the pylorus and
      forestomach ligation. Animals were sacrificed after 6 h and evaluated for the
      gastric pH, volume of gastric juices, total acidity, esophagitis index and free
      acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH,
      catalase and SOD. RESULTS: Treatment with omeprazole and baclofen significantly
      inhibited the gastric secretion, total acidity and esophagitis index. The
      treatment also helped to restore the altered level's oxidative stress parameters
      to normal. CONCLUSION: The beneficial effect of omeprazole and baclofen against
      GERD could be conglomerately attributed to the antisectretory action of
      omeprazole and reduction in the tracheal lower esophageal sphincter release rate
      by baclofen.

PMID- 24905322
TI  - The pharmacokinetics of the effervescent vs. conventional tramadol/paracetamol
      fixed-dose combination tablet in patients after total gastric resection.
AB  - BACKGROUND: Tramadol/paracetamol is a fixed-dose combination prescribed for the
      relief of moderate to severe pain. The combination acts synergistically and
      guarantees the rapid onset of paracetamol and the prolonged analgesic effect of
      tramadol with good tolerability. These drugs are often used in various
      formulations in the treatment of patients with postoperative pain, e.g. after
      stomach resection. Gastrectomy leads to pathophysiological changes within the
      alimentary tract, which may affect the process of drug absorption. The aim of the
      research was an analysis of the pharmacokinetics of tramadol/paracetamol from
      effervescent and conventional tablets in patients after total gastrectomy.
      METHODS: The research was carried out on patients after gastrectomy with Roux-en
      Y reconstruction. The patients received two tramadol/paracetamol fixed-dose
      combination tablets in a single orally administered dose of 75/650 mg (2 *
      37.5/325 mg). The patients were subjected to one of the two study drug group
      with: I. effervescent tablet (ET) (n = 14; mean [SD] age, 63.4 [10.1] years;
      weight, 75.5 [15.3]kg; and BMI, 26.0 [4.6]kg/m(2)) and II. conventional tablet
      (CT) (n = 12; mean [SD] age, 66.8 [7.7] years; weight, 79.8 [17.8]kg; and BMI,
      27.4 [5.3]kg/m(2)). Blood samples were collected within 10 h after the drug
      administration. The plasma concentrations of tramadol and paracetamol were
      measured with validated HPLC (high-performance liquid chromatography) method with
      UV detection. RESULTS: The comparison of the paracetamol and tramadol C(max)
      ratio for the ET group with that of the CT group gave ratios of 1.16 [90%
      confidence interval (CI) 1.06, 1.27] and 0.86 (90% CI 0.72, 1.02), respectively.
      The comparison of the paracetamol and tramadol AUC(0-t) ratio for the ET group
      with that of the CT group showed ratios of 0.99 (90% CI 0.88, 1.10) and 1.00 (90%
      CI 0.82, 1.22), respectively. The comparison of the difference for the
      effervescent and conventional formulation gave an estimated decrease in t(max) of
      0.5 h for paracetamol and 0.13 h for tramadol. CONCLUSIONS: In view of the
      changes in the pharmacokinetics of paracetamol and tramadol in the patients after
      gastric resection for both formulations compared the conventional tablet seems to
      be more appropriate due to the comparable rate of absorption of both substances,
      higher concentrations of tramadol and comparable exposure to paracetamol.

PMID- 24905324
TI  - Protective effect of quercetin against acetic acid induced inflammatory bowel
      disease (IBD) like symptoms in rats: possible morphological and biochemical
      alterations.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is characterized by most common
      symptoms such as rectal bleeding. Lack of specific, curative treatments tempted
      us to evaluate the therapeutic efficacy of quercetin against acetic acid induced
      IBD like symptoms. METHODS: Animals were randomly divided into five groups (n =
      6): naive, control, sulphasalazine and quercetin, and were pretreated for three
      days. Colitis was induced by intra-rectal administration of 3% acetic acid.
      RESULTS: Pretreatment with sulphasalazine or quercetin significantly attenuated
      the biochemical and morphological alterations in the colon induced by acetic acid
      in rats. CONCLUSIONS: The findings of the study suggest the possible role of
      quercetin as therapeutics in IBD.

PMID- 24905327
TI  - Self-assembly of pyrene derivatives on Au(111): substituent effects on
      intermolecular interactions.
AB  - The adsorption behaviour as well as the influence of bromine substituents on the
      formation of highly-ordered two-dimensional structures of pyrene derivatives on
      Au(111) are studied by a combination of scanning tunnelling microscopy (STM) and
      density functional theory (DFT) calculations. 

PMID- 24905325
TI  - Inhibition of sphingosine kinase-2 ablates androgen resistant prostate cancer
      proliferation and survival.
AB  - BACKGROUND: Endogenous sphingolipid signaling has been shown to play an important
      role in prostate cancer endocrine resistance. METHODS: The novel SphK2 inhibitor,
      ABC294640, was used to explore SphK signaling in androgen resistant prostate
      cancer cell death signaling. RESULTS: It dose-dependently decreased PC-3 and
      LNCaP cell viability, IC(50) of 28 +/- 6.1 MUM (p < 0.05) and 25 +/- 4.0 MUM (p <
      0.05), respectively. ABC294640 was more potent in long-term clonogenic survival
      assays; IC(50) of 14 +/- 0.4 MUM (p < 0.05) in PC-3 cells and 12 +/- 0.9 MUM (p <
      0.05) in LNCaP cells. Intrinsic apoptotic assays failed to demonstrate increased
      caspase-9 activity. Ki-67 staining demonstrated decreased proliferation by 50 +/-
      8.4% (p < 0.01) in PC-3 cells. CONCLUSIONS: SphK2 inhibition decreases androgen
      resistant prostate cancer viability, survival, and proliferation independently of
      the intrinsic apoptotic pathway. Findings are in contrast to recent observations
      of ABC29460 acting dependently on the intrinsic pathway in other endocrine
      resistant cancer cell lines.

PMID- 24905326
TI  - Oral dosing in adult zebrafish: proof-of-concept using pharmacokinetics and
      pharmacological evaluation of carbamazepine.
AB  - BACKGROUND AND METHODS: We describe a method for obtaining pharmacokinetics (PK)
      and pharmacology data from adult zebrafish in terms of mg/kg using a novel method
      of oral administration. Using carbamazepine (CBZ) as a test drug, we employed
      dried blood spot (DBS) cards to enable drug quantification for PK; and we
      evaluated the pharmacological anxiolytic effect using novel tank test. RESULTS:
      The PK study confirmed the presence of CBZ in both blood and brain and the
      behavioural study showed dose dependent anxiolytic effect. The reproducibility of
      oral dosing was confirmed by the fact that the results obtained in both the
      experiments had negligible errors. CONCLUSIONS: This report enables a novel
      approach for optimizing the utility of zebrafish in drug discovery and drug
      delivery research.

PMID- 24905328
TI  - Investigations of scope and mechanism of nickel-catalyzed transformations of
      glycosyl trichloroacetimidates to glycosyl trichloroacetamides and subsequent,
      atom-economical, one-step conversion to alpha-urea-glycosides.
AB  - The development and mechanistic investigation of a highly stereoselective
      methodology for preparing alpha-linked-urea neo-glycoconjugates and pseudo
      oligosaccharides is described. This two-step procedure begins with the selective
      nickel-catalyzed conversion of glycosyl trichloroacetimidates to the
      corresponding alpha-trichloroacetamides. The alpha-selective nature of the
      conversion is controlled with a cationic nickel(II) catalyst, [Ni(dppe)(OTf)2 ]
      (dppe=1,2-bis(diphenylphosphino)ethane, OTf=triflate). Mechanistic studies have
      identified the coordination of the nickel catalyst with the equatorial C2 -ether
      functionality of the alpha-glycosyl trichloroacetimidate to be paramount for
      achieving an alpha-stereoselective transformation. A cross-over experiment has
      indicated that the reaction does not proceed in an exclusively intramolecular
      fashion. The second step in this sequence is the direct conversion of alpha
      glycosyl trichloroacetamide products into the corresponding alpha-urea glycosides
      by reacting them with a wide variety of amine nucleophiles in presence of cesium
      carbonate. Only alpha-urea-product formation is observed, as the reaction
      proceeds with complete retention of stereochemical integrity at the anomeric C?N
      bond. 

PMID- 24905329
TI  - Combined physical activity/sedentary behaviour associations with indices of
      adiposity in 8- to 10-year-old children.
AB  - OBJECTIVE: Individuals may achieve high physical activity (PA) yet also be highly
      sedentary (SED). This study assessed adiposity in children classified by PA/SED
      groups. METHODS: Participants were 520 8- to 10-year-old children with >= 1 obese
      parent. Moderate-to-vigorous PA (MVPA) and SED were measured by accelerometer,
      and screen-time was measured by self-report. Height, weight, waist circumference
      (WC), body fat percentage (BF%), and VO2peak were objectively measured; energy
      intake was measured by dietary recall. Elevated adiposity was defined as BMI >=
      85th percentile, WC >= 90th percentile, BF% >= 85th percentile, or waist-to
      height ratio (WHR) >= 0.5. RESULTS: Up to 27% of boys and 15% of girls were
      active/SED. Adiposity was lowest for active/non-SED, highest for inactive/SED,
      and intermediate and similar for active/SED and inactive/non-SED. Using 60 min/d
      MVPA and 2 h/d screen-time cut-offs, prevalence ranges for elevated adiposity in
      the active/non-SED, active/SED, inactive/non-SED, and inactive/SED groups were 0%
      to 14%, 15% to 44%, 16% to 40%, and 32% to 51%, respectively. Corresponding odds
      and 95% confidence intervals of being overweight/obese for the latter groups were
      3.8 (95% CI, 1.7-8.4), 3.8 (1.8-8.2), and 4.9 (2.3-10.3) versus active/non-SED.
      PA/SED-adiposity associations were mediated by fitness but not energy intake.
      CONCLUSIONS: Combined PA/SED levels are strongly associated with adiposity in
      children, but associations are mediated by fitness. Active children who
      accumulate >2 h/d of screen time and inactive children are equally likely to be
      overweight/obese.

PMID- 24905330
TI  - The basic helix-loop-helix/leucine zipper transcription factor USF2 integrates
      serum-induced PAI-1 expression and keratinocyte growth.
AB  - Plasminogen activator inhibitor type-1 (PAI-1), a major regulator of the plasmin
      dependent pericellular proteolytic cascade, is prominently expressed during the
      tissue response to injury although the factors that impact PAI-1 induction and
      their role in the repair process are unclear. Kinetic modeling using established
      biomarkers of cell cycle transit (c-MYC; cyclin D1; cyclin A) in synchronized
      human (HaCaT) keratinocytes, and previous cytometric assessments, indicated that
      PAI-1 transcription occurred early after serum-stimulation of quiescent (G0)
      cells and prior to G1 entry. It was established previously that differential
      residence of USF family members (USF1->USF2 switch) at the PE2 region E box
      (CACGTG) characterized the G0  -> G1 transition period and the transcriptional
      status of the PAI-1 gene. A consensus PE2 E box motif (5'-CACGTG-3') at
      nucleotides -566 to -561 was required for USF/E box interactions and serum
      dependent PAI-1 transcription. Site-directed CG -> AT substitution at the two
      central nucleotides inhibited formation of USF/probe complexes and PAI-1 promoter
      driven reporter expression. A dominant-negative USF (A-USF) construct or double
      stranded PE2 "decoy" attenuated serum- and TGF-beta1-stimulated PAI-1 synthesis.
      Tet-Off induction of an A-USF insert reduced both PAI-1 and PAI-2 transcripts
      while increasing the fraction of Ki-67(+) cells. Conversely, overexpression of
      USF2 or adenoviral-delivery of a PAI-1 vector inhibited HaCaT colony expansion
      indicating that the USF1 -> USF2 transition and subsequent PAI-1 transcription
      are critical events in the epithelial go-or-grow response. Collectively, these
      data suggest that USF2, and its target gene PAI-1, regulate serum-stimulated
      keratinocyte growth, and likely the cadence of cell cycle progression in
      replicatively competent cells as part of the injury repair program.

PMID- 24905331
TI  - Response of rocky reef top predators (Serranidae: Epinephelinae) in and around
      marine protected areas in the Western Mediterranean Sea.
AB  - Groupers species are extremely vulnerable to overfishing and many species are
      threatened worldwide. In recent decades, Mediterranean groupers experienced
      dramatic population declines. Marine protected areas (MPAs) can protect
      populations inside their boundaries and provide individuals to adjacent fishing
      areas through the process of spillover and larval export. This study aims to
      evaluate the effectiveness of six marine reserves in the Western Mediterranean
      Sea to protect the populations of three species of grouper, Epinephelus
      marginatus, Epinephelus costae and Mycteroperca rubra, and to understand in which
      circumstances MPAs are able to export biomass to neighbouring areas. All the
      studied MPAs, except one where no grouper was observed, were able to maintain
      high abundance, biomass and mean weight of groupers. Size classes were more
      evenly distributed inside than outside MPAs. In two reserves, biomass gradients
      could be detected through the boundaries of the reserve as an indication of
      spillover. In some cases, habitat structure appeared to exert a great influence
      on grouper abundance, biomass and mean individual weight, influencing the
      gradient shape. Because groupers are generally sedentary animals with a small
      home range, we suggest that biomass gradients could only occur where groupers
      attain sufficient abundance inside MPA limits, indicating a strongly density
      dependent process. 

PMID- 24905333
TI  - Transcatheter occlusion of large pulmonary arteriovenous malformations using
      multiple devices in a neonate.
AB  - Pulmonary arteriovenous malformations (PAVMs) are usually well-tolerated
      hemodynamically. Rarely, they cause severe neonatal cyanosis, requiring urgent
      treatment. We report the use of multiple transcatheter vascular occlusion devices
      to reduce right-to-left shunting in a neonate with multiple, large PAVMs.

PMID- 24905334
TI  - Dog mitochondrial genome sequencing to enhance dog mtDNA discrimination power in
      forensic casework.
AB  - A Belgian dog population sample and several population studies worldwide have
      confirmed that only a limited number of mtDNA control region haplotypes is
      observed in the majority of dogs. The high population frequency of these
      haplotypes negatively impacts both the exclusion probability of dog mtDNA
      analysis and the evidential value of a match with one of these haplotypes in
      casework. Variation within the mtDNA coding region was explored to improve the
      discrimination power of dog mtDNA analysis. In the current study, the entire
      mitochondrial genome of 161 dogs was sequenced applying a quality assured
      strategy and resulted in a total of 119 different mitochondrial genome sequences.
      Our research was focused on those dogs with the six most common control region
      haplotypes from a previous Belgian population study. We identified 33 informative
      SNPs that successfully divide the six most common control region haplotypes into
      32 clusters of mitochondrial genome sequences. Determining the identity of these
      33 polymorphic sites in addition to control region sequencing in case of a match
      with one of these 6 control region haplotypes could augment the exclusion
      probability of forensic dog mtDNA analysis from 92.5% to 97.5%. 

PMID- 24905332
TI  - Uridine 5'-triphosphate promotes in vitro Schwannoma cell migration through
      matrix metalloproteinase-2 activation.
AB  - In response to peripheral nerve injury, Schwann cells adopt a migratory phenotype
      and modify the extracellular matrix to make it permissive for cell migration and
      axonal re-growth. Uridine 5'-triphosphate (UTP) and other nucleotides are
      released during nerve injury and activate purinergic receptors expressed on the
      Schwann cell surface, but little is known about the involvement of purine
      signalling in wound healing. We studied the effect of UTP on Schwannoma cell
      migration and wound closure and the intracellular signaling pathways involved. We
      found that UTP treatment induced Schwannoma cell migration through activation of
      P2Y2 receptors and through the increase of extracellular matrix metalloproteinase
      2 (MMP-2) activation and expression. Knockdown P2Y2 receptor or MMP-2 expression
      greatly reduced wound closure and MMP-2 activation induced by UTP. MMP-2
      activation evoked by injury or UTP was also mediated by phosphorylation of all 3
      major mitogen-activated protein kinases (MAPKs): JNK, ERK1/2, and p38. Inhibition
      of these MAPK pathways decreased both MMP-2 activation and cell migration.
      Interestingly, MAPK phosphorylation evoked by UTP exhibited a biphasic pattern,
      with an early transient phosphorylation 5 min after treatment, and a late and
      sustained phosphorylation that appeared at 6 h and lasted up to 24 h. Inhibition
      of MMP-2 activity selectively blocked the late, but not the transient, phase of
      MAPK activation. These results suggest that MMP-2 activation and late MAPK
      phosphorylation are part of a positive feedback mechanism to maintain the
      migratory phenotype for wound healing. In conclusion, our findings show that
      treatment with UTP stimulates in vitro Schwannoma cell migration and wound repair
      through a MMP-2-dependent mechanism via P2Y2 receptors and MAPK pathway
      activation. 

PMID- 24905336
TI  - Error rates in forensic DNA analysis: definition, numbers, impact and
      communication.
AB  - Forensic DNA casework is currently regarded as one of the most important types of
      forensic evidence, and important decisions in intelligence and justice are based
      on it. However, errors occasionally occur and may have very serious consequences.
      In other domains, error rates have been defined and published. The forensic
      domain is lagging behind concerning this transparency for various reasons. In
      this paper we provide definitions and observed frequencies for different types of
      errors at the Human Biological Traces Department of the Netherlands Forensic
      Institute (NFI) over the years 2008-2012. Furthermore, we assess their actual and
      potential impact and describe how the NFI deals with the communication of these
      numbers to the legal justice system. We conclude that the observed relative
      frequency of quality failures is comparable to studies from clinical laboratories
      and genetic testing centres. Furthermore, this frequency is constant over the
      five-year study period. The most common causes of failures related to the
      laboratory process were contamination and human error. Most human errors could be
      corrected, whereas gross contamination in crime samples often resulted in
      irreversible consequences. Hence this type of contamination is identified as the
      most significant source of error. Of the known contamination incidents, most were
      detected by the NFI quality control system before the report was issued to the
      authorities, and thus did not lead to flawed decisions like false convictions.
      However in a very limited number of cases crucial errors were detected after the
      report was issued, sometimes with severe consequences. Many of these errors were
      made in the post-analytical phase. The error rates reported in this paper are
      useful for quality improvement and benchmarking, and contribute to an open
      research culture that promotes public trust. However, they are irrelevant in the
      context of a particular case. Here case-specific probabilities of undetected
      errors are needed. These should be reported, separately from the match
      probability, when requested by the court or when there are internal or external
      indications for error. It should also be made clear that there are various other
      issues to consider, like DNA transfer. Forensic statistical models, in particular
      Bayesian networks, may be useful to take the various uncertainties into account
      and demonstrate their effects on the evidential value of the forensic DNA
      results. 

PMID- 24905337
TI  - Direct amplification of casework bloodstains using the Promega PowerPlex((r)) 21
      PCR amplification system.
AB  - A significant number of evidence items submitted to Forensic Science Service
      Tasmania (FSST) are blood swabs or bloodstained items. Samples from these items
      routinely undergo phenol:chloroform:isoamyl alcohol organic extraction and
      quantitative Polymerase Chain Reaction (qPCR) testing prior to PowerPlex((r)) 21
      amplification. This multi-step process has significant cost and timeframe
      implications in a fiscal climate of tightening government budgets, pressure
      towards improved operating efficiencies, and an increasing emphasis on rapid
      techniques better supporting intelligence-led policing. Direct amplification of
      blood and buccal cells on cloth and Whatman FTATM card with PowerPlex((r)) 21 has
      already been successfully implemented for reference samples, eliminating the
      requirement for sample pre-treatment. Scope for expanding this method to include
      less pristine casework blood swabs and samples from bloodstained items was
      explored in an endeavour to eliminate lengthy DNA extraction, purification and
      qPCR steps for a wider subset of samples. Blood was deposited onto a range of
      substrates including those historically found to inhibit STR amplification.
      Samples were collected with micro-punch, micro-swab, or both. The potential for
      further fiscal savings via reduced volume amplifications was assessed by
      amplifying all samples at full and reduced volume (25 and 13MUL). Overall success
      rate data showed 80% of samples yielded a complete profile at reduced volume,
      compared to 78% at full volume. Particularly high success rates were observed for
      the blood on fabric/textile category with 100% of micro-punch samples yielding
      complete profiles at reduced volume and 85% at full volume. Following the success
      of this trial, direct amplification of suitable casework blood samples has been
      implemented at reduced volume. Significant benefits have been experienced, most
      noticeably where results from crucial items have been provided to police
      investigators prior to interview of suspects, and a coronial identification has
      been successfully completed in a short timeframe to avoid delay in the release of
      human remains to family members. 

PMID- 24905335
TI  - Developmental validation of the PowerPlex((r)) Fusion System for analysis of
      casework and reference samples: A 24-locus multiplex for new database standards.
AB  - The original CODIS database based on 13 core STR loci has been overwhelmingly
      successful for matching suspects with evidence. Yet there remain situations that
      argue for inclusion of more loci and increased discrimination. The PowerPlex((r))
      Fusion System allows simultaneous amplification of the following loci:
      Amelogenin, D3S1358, D1S1656, D2S441, D10S1248, D13S317, Penta E, D16S539,
      D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX,
      DYS391, D8S1179, D12S391, D19S433, FGA, and D22S1045. The comprehensive list of
      loci amplified by the system generates a profile compatible with databases based
      on either the expanded CODIS or European Standard Set (ESS) requirements.
      Developmental validation testing followed SWGDAM guidelines and demonstrated the
      quality and robustness of the PowerPlex((r)) Fusion System across a number of
      variables. Consistent and high-quality results were compiled using data from 12
      separate forensic and research laboratories. The results verify that the
      PowerPlex((r)) Fusion System is a robust and reliable STR-typing multiplex
      suitable for human identification. 

PMID- 24905338
TI  - A simple identification method for vaginal secretions using relative
      quantification of Lactobacillus DNA.
AB  - In criminal investigations there are some cases in which identifying the presence
      of vaginal secretions provides crucial evidence in proving sexual assault.
      However, there are no methods for definitively identifying vaginal secretions. In
      the present study, we focused on Lactobacillus levels in vaginal secretions and
      developed a novel identification method for vaginal secretions by relative
      quantification based on real time PCR. We designed a Lactobacillus conserved
      region primer pair (LCP) by aligning 16S rRNA gene sequences from major vaginal
      Lactobacillus species (Lactobacillus crispatus, Lactobacillus gasseri,
      Lactobacillus iners and Lactobacillus jensenii), and selected the human specific
      primer pair (HSP) as an endogenous control for relative quantification. As a
      result, the DeltaCt (DeltaCt=Ct[LCP]-Ct[HSP]) values of vaginal secretions (11
      out of 12 samples) were significantly lower than those of saliva, semen and skin
      surface samples, and it was possible to discriminate between vaginal secretions
      and other body fluids. For the one remaining sample, it was confirmed that the
      predominant species in the microflora was not of the Lactobacillus genus. The
      DeltaCt values in this study were calculated when the total DNA input used from
      the vaginal secretions was 10pg or more. Additionally, the DeltaCt values of
      samples up to 6-months-old, which were kept at room temperature, remained
      unchanged. Thus, we concluded in this study that the simple DeltaCt method by
      real time PCR is a useful tool for detecting the presence of vaginal secretions. 

PMID- 24905339
TI  - Nanofiber: Synthesis and biomedical applications.
AB  - Electrospinning uses an electrical charge to draw very fine (typically on the
      micro or nano scale) fibers from a liquid. Electrospinning or electrostatic
      spinning shares characteristics of both electrospraying and conventional solution
      dry spinning of fibers. The method does not need the use of coagulation chemistry
      or high temperatures to produce solid threads from solution. This makes the
      process particularly suited for the production of fibers using large and complex
      molecules. Because the full potential of biomaterials being used in various
      applications, field of nanofibers have involved considerable interest in
      biotechnology and medicine and there has been fast development in this area in
      recent years. 

PMID- 24905340
TI  - Ameliorative role of gemfibrozil against partial abdominal aortic constriction
      induced cardiac hypertrophy in rats.
AB  - Fibrates are peroxisome proliferator-activated receptor-alpha agonists and are
      clinically used for treatment of dyslipidemia and hypertriglyceridemia.
      Fenofibrate is reported as a cardioprotective agent in various models of cardiac
      dysfunction; however, limited literature is available regarding the role of
      gemfibrozil as a possible cardioprotective agent, especially in a non-obese model
      of cardiac remodelling. The present study investigated the role of gemfibrozil
      against partial abdominal aortic constriction-induced cardiac hypertrophy in
      rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in
      rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by
      measuring left ventricular weight to body weight ratio, left ventricular wall
      thickness, and protein and collagen content. The oxidative stress in the cardiac
      tissues was assessed by measuring thiobarbituric acid-reactive substances,
      superoxide anion generation, and reduced glutathione level. The haematoxylin
      eosin and picrosirius red staining was used to observe cardiomyocyte diameter and
      collagen deposition, respectively. Moreover, serum levels of cholesterol, high
      density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil
      (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic
      constriction and continued for 4 weeks. The partial abdominal aortic constriction
      induced cardiac oxidative stress and hypertrophy are indicated by significant
      change in various parameters used in the present study that were ameliorated with
      gemfibrozil treatment in rats. No significant change in serum parameters was
      observed between various groups used in the present study. It is concluded that
      gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac
      oxidative stress and hypertrophy and in rats. 

PMID- 24905342
TI  - An 18-gene signature for vascular invasion is associated with aggressive features
      and reduced survival in breast cancer.
AB  - AIMS: Vascular invasion by tumor cells is known to be important for cancer
      progression. By microarray and qPCR analyses, we earlier identified an 18-gene
      signature associated with vascular involvement in endometrial cancer. Here, we
      explored the significance of this vascular invasion signature in multiple series
      of breast cancer patients. METHODS AND RESULTS: The study includes 11 open access
      gene expression data sets which collectively provide information on 2423 breast
      cancer patients. The 18-gene signature showed consistent associations with
      aggressive features of breast cancer, like high tumor grade, hormone receptor
      negativity, HER2 positivity, a basal-like phenotype, reduced patient survival,
      and response to neoadjuvant chemotherapy. Also, the vascular invasion signature
      was associated with several other gene expression profiles related to vascular
      biology and tumor progression, including the Oncotype DX breast cancer recurrence
      signature. CONCLUSIONS: The 18-gene vascular invasion signature showed strong and
      consistent associations with aggressive features of breast cancer and reduced
      survival.

PMID- 24905343
TI  - Patient selection and the volume effect in pancreatic surgery: unequal benefits?
AB  - BACKGROUND: The volume effect in pancreatic surgery is well established.
      Regionalization to high-volume centres has been proposed. The effect of this
      proposal on practice patterns is unknown. METHODS: Retrospective review of
      pancreatectomy patients in the Nationwide Inpatient Sample 2004-2011. Inpatient
      mortality and complication rates were calculated. Patients were stratified by
      annual centre pancreatic resection volume (low <5, medium 5-18, high >18).
      Multivariable regression model evaluated predictors of resection at a high-volume
      centre. RESULTS: In total, 129,609 patients underwent a pancreatectomy. The crude
      inpatient mortality rate was 4.3%. 36.0% experienced complications. 66.5%
      underwent a resection at high-volume centres. In 2004, low-, medium- and high
      volume centres resected 16.3%, 24.5% and 59.2% of patients, compared with 7.6%,
      19.3% and 73.1% in 2011. High-volume centres had lower mortality (P < 0.001),
      fewer complications (P < 0.001) and a shorter median length of stay (P < 0.001).
      Patients at non-high-volume centres had more comorbidities (P = 0.001), lower
      rates of private insurance (P < 0.001) and more non-elective admissions (P <
      0.001). DISCUSSION: In spite of a shift to high-volume hospitals, a substantial
      cohort still receives a resection outside of these centres. Patients receiving
      non-high-volume care demonstrate less favourable comorbidities, insurance and
      urgency of operation. The implications are twofold: already disadvantaged
      patients may not benefit from the high-volume effect; and patients predisposed to
      do well may contribute to observed superior outcomes at high-volume centres.

PMID- 24905344
TI  - Atg37 regulates the assembly of the pexophagic receptor protein complex.
AB  - Like other selective autophagy pathways, the selective autophagy of peroxisomes,
      pexophagy, is controlled by receptor protein complexes (RPCs). The pexophagic RPC
      in Pichia pastoris consists of several proteins: Pex3 and Pex14 ligands in the
      peroxisomal membrane, Atg30 receptor, Atg11, and Atg17 scaffolds, and the
      phagophore protein Atg8. Recently, we identified a new component of the
      pexophagic RPC, Atg37, which is involved in the assembly of this complex. Atg37
      is an integral peroxisomal membrane protein (PMP) that binds Pex3 and Atg30, but
      not Pex14 or Atg8. In the absence of Atg37, the recognition of Pex3 and
      recruitment of Atg17 by Atg30 are normal. However, the recruitment of Atg11 is
      severely affected suggesting that the role of Atg37 is to facilitate the Atg30
      Atg11 interaction. Palmitoyl-CoA competes with Atg30 for the acyl-CoA binding
      domain of Atg37 in vitro and might regulate the dynamics of the pexophagic RPC in
      vivo. The human counterpart of Atg37, ACBD5, also localizes to peroxisomes and is
      specifically required for pexophagy. Therefore, it is tempting to speculate that
      ACBD5/ATG37 regulates the assembly of the pexophagic RPC in mammalian cells. 

PMID- 24905345
TI  - Is a coded physical activity diary valid for assessing physical activity level
      and energy expenditure in stroke patients?
AB  - OBJECTIVES: to determine the concurrent validity of a physical activity diary for
      measuring physical activity level and total energy expenditure in hospitalized
      stroke patients. METHOD: Sixteen stroke patients kept coded activity diaries and
      wore SenseWear Pro2 multi-sensor activity monitors during daytime hours for one
      day. A researcher observed the patients and completed a diary. Data from the
      patients' diaries were compared with observed and measured data to determine
      total activity (METs*minutes), activity level and total energy expenditure.
      RESULTS: Spearman correlations between the patients' and researchers' diaries
      revealed a high correlation for total METs*minutes (rs = 0.75, p<0.01) for
      sedentary (rs = 0.74,p<0.01) and moderate activities (rs = 0.71,p<0.01) and a
      very high correlation (rs = 0.92, p<0.01) for the total energy expenditure.
      Comparisons between the patients' diaries and activity monitor data revealed a
      low correlation (rs 0.29) for total METs*minutes and energy expenditure.
      CONCLUSION: Coded self-monitoring activity diaries appear feasible as a low-tech
      alternative to labor-intensive observational diaries for determining sedentary,
      moderate, and total physical activity and for quantifying energy expenditure in
      hospitalized stroke patients. Given the poor correlation with objective
      measurements of physical activity, however, further research is needed to
      validate its use against a gold-standard measure of physical activity intensity
      and energy expenditure.

PMID- 24905347
TI  - Dearomatization-induced transannular cyclization: synthesis of electron-accepting
      thiophene-S,S-dioxide-fused biphenylene.
AB  - The transannular cyclization of dehydroannulenes bearing several alkyne moieties
      in close proximity is a powerful synthetic method for producing polycyclic
      aromatic hydrocarbons. We report that the reactivity can be switched by the
      aromaticity of the ring skeletons fused with the dehydroannulene core. Thus,
      while thiophene-fused bisdehydro[12]annulene 1 was handled as a stable compound
      in the air at room temperature, the oxidation with m-chloroperbenzoic acid from
      the aromatic thiophene rings to the nonaromatic thiophene-S,S-dioxides induced
      the transannular cyclization, even at room temperature, which was completed
      within 1 day to produce the formal [2 + 2] cycloadduct 3. This is in stark
      contrast to the fact that the thermal cyclization of 1 itself required heating at
      80  degrees C for 9 days for completion. Experimental and theoretical studies
      indicate that the oxidation of even one thiophene ring in 1 sufficiently
      decreases the activation barrier for the transannular cyclization that proceeds
      through the 8pi and 4pi electrocyclic reaction sequence. The thiophene-S,S
      dioxide-fused biphenylene 3 thus produced exhibits a set of intriguing
      properties, such as a higher electron affinity (E1/2 = -1.17 V vs Fc and Fc(+))
      and a stronger fluorescence (PhiF = 0.20) than the other relevant biphenylene
      derivatives, which have electron-donating and nonfluorescent characteristics. 

PMID- 24905346
TI  - Exposure to Beta-(1,3)-D-glucan in house dust at age 7-10 is associated with
      airway hyperresponsiveness and atopic asthma by age 11-14.
AB  - BACKGROUND: Mould exposure has been linked to childhood asthma and bronchial
      hyper-responsiveness. Few studies have assessed beta-(1,3)-d-glucan (beta
      glucan), a significant fungal cell wall constituent, in relation to asthma in
      adolescence. OBJECTIVE: To determine whether house dust-derived beta-glucan
      exposure at age 7-10 is associated with the development and persistence of atopic
      and non-atopic asthma, and bronchial hyper-responsiveness (BHR) by age 11-14.
      METHODS: Dust samples were collected from the 1995 Study of Asthma, Genes, and
      Environment (SAGE) birth cohort. This cohort was derived from Manitoba provincial
      healthcare administrative records of children high and low risk for asthma.
      Samples were collected from the homes of 422 children at age 7-10 and analyzed
      using beta-glucan and endotoxin-specific Limulus Amoebocyte Lysate assays.
      Asthma, atopy, and BHR status of each child were also assessed at ages 7-10 and
      11-14. RESULTS: At age 7-10, beta-glucan dust levels in the home were associated
      with persistent atopic asthma at age 11-14 (OR 1.79 for each unit increase in
      levels, 95% CI 1.14-2.81), independent of endotoxin exposure, and Alternaria or
      Cladosporium sensitization. The likelihood of BHR almost doubled with unit
      increases in dust beta-glucan in asthmatic children. In children without asthma,
      exposure to high beta-glucan levels at age 7-10 also elevated risk for BHR in
      adolescence (OR 1.74, 95% CI 1.05-2.89). New-onset atopic asthma was twice more
      likely following high beta-glucan exposure in children without asthma but the
      association did not reach statistical significance. No associations were evident
      with concurrent asthma phenotype at age 7-10 or non-atopic asthma at age 11-14.
      CONCLUSION: These findings implicate home beta-glucan exposure at school-age as a
      risk factor for persistent atopic asthma and new-onset BHR. The higher prevalence
      of BHR in urban adolescents may be propagated by this home exposure.

PMID- 24905348
TI  - Risk versus risk: a review of benzodiazepine reduction in older adults.
AB  - INTRODUCTION: Benzodiazepines (BZD) are potentially inappropriate for older
      adults, yet their use persists. Patients and providers may hesitate to
      discontinue BZDs due to concerns for withdrawal or relapse. We reviewed the
      literature for BZD reduction protocols to examine common elements, safety and
      efficacy. A framework is proposed for clinicians to address BZD reduction
      challenges. AREAS COVERED: Following a systematic literature review, this
      analysis included 28 studies of older out-patients tapering chronic BZDs.
      Populations included insomnia, depression and anxiety. Protocols included taper
      alone (32%), taper plus cognitive behavioral therapy (32%) and taper plus
      medication substitution (36%). Success rates were favorable for all modalities
      (mean 60%, median 67%, range 25 - 85%) and independent of dose or duration of
      use. Common schedules included a 25% dose reduction over 1 - 2 weeks until drug
      free. Withdrawal symptoms included mainly mild psychological and somatic
      concerns. No serious safety events were reported. EXPERT OPINION: BZD reduction
      protocols among older adults are feasible and successful. Given unique cognitive
      and functional abilities and comorbidities of older adults, a patient-centered
      approach to reduction is needed. Our framework guides clinicians in planning and
      persisting with BZD reduction, while our checklist addresses tailored tapers.
      Monitoring and support is emphasized, and taper modifications are proposed for
      struggling patients.

PMID- 24905349
TI  - Power and fairness in a generalized ultimatum game.
AB  - Power is the ability to influence others towards the attainment of specific
      goals, and it is a fundamental force that shapes behavior at all levels of human
      existence. Several theories on the nature of power in social life exist,
      especially in the context of social influence. Yet, in bargaining situations,
      surprisingly little is known about its role in shaping social preferences. Such
      preferences are considered to be the main explanation for observed behavior in a
      wide range of experimental settings. In this work, we set out to understand the
      role of bargaining power in the stylized environment of a Generalized Ultimatum
      Game (GUG). We modify the payoff structure of the standard Ultimatum Game (UG) to
      investigate three situations: two in which the power balance is either against
      the proposer or against the responder, and a balanced situation. We find that
      other-regarding preferences, as measured by the amount of money donated by
      participants, do not change with the amount of power, but power changes the
      offers and acceptance rates systematically. Notably, unusually high acceptance
      rates for lower offers were observed. This finding suggests that social
      preferences may be invariant to the balance of power and confirms that the role
      of power on human behavior deserves more attention. 

PMID- 24905350
TI  - Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a
      previously unrecognized mechanism for acrolein-mediated oxidative stress.
AB  - Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress,
      readily reacts with a variety of nucleophilic biomolecules. Polyamines, which
      produced acrolein in the presence of amine oxidase, were then found to react with
      acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but
      significant downstream product of oxidative stress. Although diazacyclooctane
      formation effectively neutralized acrolein toxicity, the diazacyclooctane
      hydrogel produced through a sequential diazacyclooctane polymerization reaction
      was highly cytotoxic. This study suggests that diazacyclooctane formation is
      involved in the mechanism underlying acrolein-mediated oxidative stress. 

PMID- 24905351
TI  - Psychological and drug abuse symptoms associated with nonmedical use of opioid
      analgesics among adolescents.
AB  - BACKGROUND: Approximately 18% of US adolescents engaged in prescription opioid
      abuse in 2013. However, this estimate may be misleading because it includes both
      medical misusers and nonmedical users, and there is evidence that these are 2
      groups that differ relative to substance abuse and criminal risk. Thus, this
      study does not combine medical and nonmedical users; rather, it seeks to better
      understand the characteristics of nonmedical users. METHODS: This was a school
      based, cross-sectional study that was conducted during 2009-2010 in southeastern
      Michigan with a sample of 2627 adolescents using a Web-based survey. Three
      mutually exclusive groups were created based on responses regarding medical and
      nonmedical use of opioid analgesics. Group 1 had never used an opioid analgesic,
      Group 2 used an opioid analgesic only as prescribed, and Group 3 nonmedically
      used an opioid analgesic. In addition, Group 3 was divided into 2 mutually
      exclusive subgroups (self-treaters and sensation-seekers) based on reasons for
      nonmedical use. A series of multinomial logistic regressions were conducted to
      determine if the groups differed on the presence of pain, psychological symptoms
      (e.g., affective disorder, conduct disorder, attention-deficit/hyperactivity
      disorder [ADHD]), and drug abuse. RESULTS: Sixty-five percent (65.0%) of the
      sample was white/Caucasian and 29.5% was African American. The average age was
      14.8 years (SD = 1.9). Seventy percent (70.4%; n = 1850) reported no lifetime
      opioid use, 24.5% (n = 644) were medical users, 3.5% (n = 92) were nonmedical
      users who used for pain relief only, and 1.6% (n = 41) were classified as
      nonmedical users for reasons other than for pain relief (e.g., to get high). Both
      medical users and nonmedical users reported more pain and substance abuse
      symptoms compared with never users. Those nonmedical users who used opioids for
      sensation-seeking motivations had greater odds of having psychological symptoms.
      CONCLUSIONS: These data support the need to further consider subgroups of
      nonmedical users of opioid analgesics.

PMID- 24905354
TI  - Nutrition 411: an introduction to herbs for wound healing professionals.

PMID- 24905355
TI  - A prospective pilot study to evaluate wound outcomes and levels of serum C
      reactive protein and interleukin-6 in the wound fluid of patients with trauma
      related chronic wounds.
AB  - If surgical closure of chronic wounds is an option, choosing an appropriate time
      to definitely close these wounds remains a challenge. Although the underlying
      mechanisms of nonhealing are not completely understood, serum C-reactive protein
      (CRP) and interleukin-6 (IL-6) in wound fluid have been found to be markers of
      the systemic and local inflammation state of chronic wounds. The purpose of this
      prospective, descriptive pilot study was to evaluate the effect of debridement,
      systemic antibiotics, and negative pressure wound therapy (NPWT) on the outcomes
      of trauma-related chronic wounds and changes in local inflammation responses,
      measured using CRP and IL-6 levels as indicators of cytokine regulation. Between
      June 2012 and May 2013, 20 consecutive patients (14 men, six women, mean age 40
      [range 17-56] years) with various trauma-related, nonhealing chronic wounds were
      enrolled in the study after failing to heal for an average of 8.5 (range 6-16)
      weeks using a protocol of regular debridement and gauze dressings. Before the
      start of the study, wounds were cultured, and laboratory values for white blood
      cell count (WBC), neutrophils, and levels of serum CRP and IL-6 in the wound
      fluid obtained. Wounds were surgically debrided and NPWT (continuous at 125 mm
      Hg) applied. All patients were prescribed systemic antibiotics, and mean time
      interval between NPWT dressing changes was 5 (range 3-7) days. During an average
      mean NPWT treatment time of 13 (range 5-20) days, CRP and IL-6 concentrations
      decreased from 66.4 mg/L to 10.4 mg/L and 44.1 pg/mL to 8.6 pg/mL, respectively
      (P <0.001). The presence/absence of bacteria, WBC, and neutrophil counts did not
      change. No complications were noted, and all wounds were successfully closed
      using various surgical procedures. In this study, clinical wound improvement and
      a significant decrease in wound fluid CRP and IL-6 levels were observed. Studies
      with a larger sample size and a more robust study design may help elucidate the
      relationship between inflammatory molecules, infection, and healing outcomes. 

PMID- 24905353
TI  - New insights into 1-aminocyclopropane-1-carboxylate (ACC) deaminase phylogeny,
      evolution and ecological significance.
AB  - The main objective of this work is the study of the phylogeny, evolution and
      ecological importance of the enzyme 1-aminocyclopropane-1-carboxylate (ACC)
      deaminase, the activity of which represents one of the most important and studied
      mechanisms used by plant growth-promoting microorganisms. The ACC deaminase gene
      and its regulatory elements presence in completely sequenced organisms was
      verified by multiple searches in diverse databases, and based on the data
      obtained a comprehensive analysis was conducted. Strain habitat, origin and ACC
      deaminase activity were taken into account when analyzing the results. In order
      to unveil ACC deaminase origin, evolution and relationships with other closely
      related pyridoxal phosphate (PLP) dependent enzymes a phylogenetic analysis was
      also performed. The data obtained show that ACC deaminase is mostly prevalent in
      some Bacteria, Fungi and members of Stramenopiles. Contrary to previous reports,
      we show that ACC deaminase genes are predominantly vertically inherited in
      various bacterial and fungal classes. Still, results suggest a considerable
      degree of horizontal gene transfer events, including interkingdom transfer
      events. A model for ACC deaminase origin and evolution is also proposed. This
      study also confirms the previous reports suggesting that the Lrp-like regulatory
      protein AcdR is a common mechanism regulating ACC deaminase expression in
      Proteobacteria, however, we also show that other regulatory mechanisms may be
      present in some Proteobacteria and other bacterial phyla. In this study we
      provide a more complete view of the role for ACC deaminase than was previously
      available. The results show that ACC deaminase may not only be related to plant
      growth promotion abilities, but may also play multiple roles in microorganism's
      developmental processes. Hence, exploring the origin and functioning of this
      enzyme may be the key in a variety of important agricultural and biotechnological
      applications. 

PMID- 24905356
TI  - A prospective, descriptive cohort study of malignant wound characteristics and
      wound care strategies in patients with breast cancer.
AB  - Few studies have addressed the effects of dressings on malignant wounds. A 20
      month (May 2010 to January 2011) descriptive, prospective cohort study was
      conducted by the Wound Care Unit of Institute Curie, Paris, France to evaluate
      the use of various local care procedures and characteristics of malignant wounds.
      Symptoms and wound management methods were observed over a period of 42 days in
      32 patients (all women, mean age 60 years, range 30-96 years, most with
      infiltrating ductal carcinoma). After cleansing (with either sterile saline or
      water), a variety of wound treatments were used based on specific wound
      characteristics, including calcium alginate, hydrocellular, interface, and active
      charcoal and superabsorbent dressings. Wound size, color (red, pink, black,
      yellow), periwound condition, surface wound organisms (number of species and
      quantity), and signs of infection, along with wound-related pain (rated on a
      verbal rating scale), odor, bleeding (spontaneous or induced), and exudate (rated
      on a four-level scale as none, slight, moderate, intense) were assessed at
      baseline and on days 21 and 42 of treatment. The degree to which each symptom was
      managed was scored as controlled, partly controlled, or not controlled. Mean
      initial wound size did not change over the evaluation period; most (74%) wounds
      were characterized as being inflamed. No infectious episodes were observed during
      the duration of the evaluation. Exudate and bleeding were generally controlled
      with hemostatic dressings, calcium alginate dressings, or absorbent pads. Odor
      was not completely controlled with charcoal dressing and was noted to be
      significantly greater in patients with >105/g bacterial counts and/or with one or
      more anaerobic bacteria (P = 0.05). At day 0, 13 out of 25 patients (50%) had
      uncontrolled pain; pain ratings did not change over the course of the study.
      Clinical research on specific clinical practice (eg, topical morphine for pain)
      and to assess the comparative efficacy of different care approaches on
      controlling the local symptoms of malignant wounds is warranted to improve the
      quality of care, which may affect patient quality of life. 

PMID- 24905352
TI  - Autophagy promotes resistance to photodynamic therapy-induced apoptosis
      selectively in colorectal cancer stem-like cells.
AB  - Recent studies have indicated that cancer stem-like cells (CSCs) exhibit a high
      resistance to current therapeutic strategies, including photodynamic therapy
      (PDT), leading to the recurrence and progression of colorectal cancer (CRC). In
      cancer, autophagy acts as both a tumor suppressor and a tumor promoter. However,
      the role of autophagy in the resistance of CSCs to PDT has not been reported. In
      this study, CSCs were isolated from colorectal cancer cells using PROM1/CD133
      (prominin 1) expression, which is a surface marker commonly found on stem cells
      of various tissues. We demonstrated that PpIX-mediated PDT induced the formation
      of autophagosomes in PROM1/CD133(+) cells, accompanied by the upregulation of
      autophagy-related proteins ATG3, ATG5, ATG7, and ATG12. The inhibition of PDT
      induced autophagy by pharmacological inhibitors and silencing of the ATG5 gene
      substantially triggered apoptosis of PROM1/CD133(+) cells and decreased the
      ability of colonosphere formation in vitro and tumorigenicity in vivo. In
      conclusion, our results revealed a protective role played by autophagy against
      PDT in CSCs and indicated that targeting autophagy could be used to elevate the
      PDT sensitivity of CSCs. These findings would aid in the development of novel
      therapeutic approaches for CSC treatment. 

PMID- 24905357
TI  - Treating peristomal pyoderma gangrenosum with topical crushed prednisone: a
      report of three cases.
AB  - The main goals of treating peristomal pyoderma gangrenosum (PPG) - ulcerations in
      the stomal area - are to decrease pain, increase pouch adherence, and decrease
      pyoderma. The literature suggests a wide variety of approaches to achieve this
      goal, but few studies report outcomes on the use of topical steroids. The purpose
      of this case study is to describe the results of a protocol developed to meet the
      goals of care for patients with PPG. Three patients presenting with PPG lesions
      were instructed to crush a 1-mg prednisone tablet for mixing with an equal part
      of a hydrocolloid powder. The mix was applied directly on the PPG lesions,
      covered with a calcium alginate (or hydrofiber) primary dressing, and secured
      with a hydrocolloid secondary dressing. The pouching system then was applied over
      the hydrocolloid dressing. Three goals of treatment were met: pain dissipated (in
      as quickly as 1 week); pouch adherence improved (within 0 to 3 days); and
      closure/healing of the lesions occurred (within 3 to 5 weeks), recurring in only
      one case in which the patient had a peristomal hernia. No side effects were
      observed. Although this self-treatment provided satisfactory results, further
      study is needed to evaluate its effectiveness in a larger population and longer
      follow-up. 

PMID- 24905359
TI  - Independent component analysis and decision trees for ECG holter recording de
      noising.
AB  - We have developed a method focusing on ECG signal de-noising using Independent
      component analysis (ICA). This approach combines JADE source separation and
      binary decision tree for identification and subsequent ECG noise removal. In
      order to to test the efficiency of this method comparison to standard filtering a
      wavelet- based de-noising method was used. Freely data available at Physionet
      medical data storage were evaluated. Evaluation criteria was root mean square
      error (RMSE) between original ECG and filtered data contaminated with artificial
      noise. Proposed algorithm achieved comparable result in terms of standard noises
      (power line interference, base line wander, EMG), but noticeably significantly
      better results were achieved when uncommon noise (electrode cable movement
      artefact) were compared. 

PMID- 24905358
TI  - Interpersonal engagement mediates the relation between maternal affect and
      externalising behaviour in young children with type 1 diabetes.
AB  - Mother-child interactions around a shared activity have been shown to play a key
      role in the development of young children's capacity to interact cooperatively
      with others. This evidence is particularly germane to type 1 diabetes (T1D)
      management in younger children where cooperation with parental treatment efforts
      is crucial for treatment success and where maternal distress and child
      behavioural problems are risk factors for treatment management, biomedical and
      psychological outcomes. In 49 4-to-8 year old children with T1D, we investigated
      whether the association between maternal affect and child problematic behaviour
      is mediated by mother-child interactions in the context of a T1D-relevant
      collaborative problem-solving activity. Mothers completed standardised measures
      of maternal and child psychological adjustment and interacted with their children
      in the problem-solving activity, analysed for quality of interpersonal engagement
      based on evaluations of maternal (sensitivity and cognitive stimulation) and
      dyadic (joint attention and warmth) behaviours. Mediation analyses confirmed the
      hypothesis that interpersonal engagement mediates the relation between maternal
      affective state and child behavioural problems. Specifically, more negative
      maternal affect is associated with lower levels of interpersonal engagement;
      these less engaged interactions in turn are associated with more behavioural
      problems in children. These findings are consistent with research involving
      typically developing children. The implications of our findings are twofold.
      First, in the context of psychological adjustment to T1D, maternal affect and
      mother-child interactions are 2 potential targets for interventions which promote
      cooperative interactions. Second, understanding and caring for children at
      biological risk requires attention to developmental psychology theory and method;
      in particular, research addressing parent-child cooperation carries both
      conceptual and clinical relevance. 

PMID- 24905360
TI  - Social variables affecting mate preferences, copulation and reproductive outcome
      in a pack of free-ranging dogs.
AB  - Mating and reproductive outcome is often determined by the simultaneous operation
      of different mechanisms like intra-sexual competition, mating preferences and
      sexual coercion. The present study investigated how social variables affected
      mating outcome in a pack of free-ranging dogs, a species supposed to have lost
      most features of the social system of wolves during domestication. We found that,
      although the pack comprised multiple breeding individuals, both male copulation
      success and female reproductive success were positively influenced by a linear
      combination of dominance rank, age and leadership. Our results also suggest that
      mate preferences affect mating outcome by reinforcing the success of most
      dominant individuals. In particular, during their oestrous period bitches clearly
      searched for the proximity of high-ranking males who displayed affiliative
      behaviour towards them, while they were more likely to reject the males who
      intimidated them. At the same time, male courting effort and male-male
      competition for receptive females appeared to be stronger in the presence of
      higher-ranking females, suggesting a male preference for dominant females. To our
      knowledge, these results provide the first clear evidence of social regulation of
      reproductive activities in domestic dogs, and suggest that some common organizing
      mechanisms may contribute to shape the social organization of both dogs and
      wolves. 

PMID- 24905361
TI  - Finding ATF4/p75NTR/IL-8 signal pathway in endothelial-mesenchymal transition by
      safrole oxide.
AB  - Targeting the endothelial-to-mesenchymal transition (EndoMT) may be a novel
      therapeutic strategy for cancer and various diseases induced by fibrosis. We
      aimed to identify a small chemical molecule as an inducer of EndoMT and find a
      new signal pathway by using the inducer. Safrole oxide (SFO), 50 ug/ml, could
      most effectively induce EndoMT within 12 h. To understand the underlying
      molecular mechanism, we performed microarray, quantitative real-time PCR and
      western blot analysis to find key factors involved in SFO-induced EndoMT and
      demonstrated the involvement of the factors by RNAi. The expression of activating
      transcription factor 4 (ATF4), p75 neurotrophin receptor (p75NTR), and
      interleukin 8 (IL-8) was greatly increased in SFO-induced EndoMT. Knockdown of
      ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8
      partially inhibited the EndoMT, which suggests that all three factors were
      involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO
      increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO
      increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may
      have an important role in EndoMT induced by SFO. Our findings support potential
      novel targets for the therapeutics of cancer and fibrosis disease. 

PMID- 24905363
TI  - Performance of adaptive designs for single-armed phase II oncology trials.
AB  - When planning a single-armed clinical trial with binary endpoint, the sample size
      is determined such that the desired power is achieved for a single value of the
      target rate. However, there is usually some uncertainty with respect to the true
      treatment effect. It is therefore more realistic to specify an interval for the
      possible true rate to accommodate this uncertainty. For this situation, we
      examine comprehensively the overall performance of various Phase II oncology
      designs and sample size recalculation strategies. The methods and results of our
      investigations can be used to identify the most appropriate approach for a
      specific clinical trial situation at hand. Application is illustrated with a
      clinical trial in rectal cancer. 

PMID- 24905362
TI  - Antigen capture and archiving by lymphatic endothelial cells following
      vaccination or viral infection.
AB  - Antigen derived from viral infections with influenza and vesicular stomatitis
      virus can persist after resolution of infection. Here we show that antigen can
      similarly persist for weeks following viral challenge and vaccination. Antigen is
      captured by lymphatic endothelial cells (LECs) under conditions that induce LEC
      proliferation. Consistent with published data showing that viral antigen
      persistence impacts the function of circulating memory T cells, we find that
      vaccine-elicited antigen persistence, found on LECs, positively influences the
      degree of protective immunity provided by circulating memory CD8(+) T cells. The
      coupling of LEC proliferation and antigen capture identifies a mechanism by which
      the LECs store, or 'archive', antigens for extended periods of time after antigen
      challenge, thereby increasing IFNgamma/IL-2 production and enhancing protection
      against infection. These findings therefore have the potential to have an impact
      on future vaccination strategies and our understanding of the role for persisting
      antigen in both vaccine and infectious settings. 

PMID- 24905364
TI  - Implementing a Public Bicycle Share Program: Impact on Perceptions and Support
      for Public Policies for Active Transportation.
AB  - BACKGROUND: Favorable public opinion and support for policies are essential to
      favor the sustainability of environmental interventions. This study examined
      public perceptions and support for active living policies associated with
      implementing a public bicycle share program (PBSP). METHODS: Two cross-sectional
      population-based telephone surveys were conducted in 2009 and 2010 among 5011
      adults in Montreal, Canada. Difference-in-differences analyses tested the impact
      of the PBSP on negative perceptions of the impact of the PBSP on the image of the
      city, road safety, ease of traveling, active transportation, health, and
      resistance to policies. RESULTS: People living closer to docking stations were
      less likely to have negative perceptions of the effect of the PBSP on the image
      of the city (OR = 0.5; 95% CI, 0.4-0.8) and to be resistant to policies (OR =
      0.8; 95% CI, 0.6-1.0). The likelihood of perceiving negative effects on road
      safety increased across time (OR = 1.4; 95% CI, 1.2-1.8). Significant
      interactions were observed for perceptions of ease of traveling (OR = 0.5; 95%
      CI, 0.4-0.8), active transportation (OR = 0.6; 95% CI, 0.4-1.0), and health (OR =
      0.6; 95% CI, 0.4-0.8): likelihood of negative perceptions decreased across time
      among people exposed. CONCLUSION: Findings indicate that negative perceptions
      were more likely to abate among those living closer to the PBSP.

PMID- 24905365
TI  - TNF-alpha gene promoter polymorphisms contribute to periodontitis susceptibility:
      evidence from 46 studies.
AB  - AIM: Tumour necrosis factor-alpha (TNF-alpha) plays a critical role in the
      pathogenesis of periodontal disease. TNF-alpha gene polymorphisms can influence
      the TNF-alpha production. Many studies have focused the association between TNF
      alpha gene promoter polymorphisms and periodontitis risk, but these results are
      still controversial. MATERIALS AND METHODS: A meta-analysis was performed to
      assess the effect of TNF-alpha -308G/A (rs1800629), -238G/A (rs361525) and 
      863C/A (rs1800630) polymorphisms on either chronic (CP) or aggressive
      periodontitis (AgP) risk. Odds ratios (ORs) along with their 95% confidence
      intervals (CIs) were calculated to assess the strength of the association. Forty
      six studies involving 5186 cases and 6683 controls were retrieved and analyzed.
      RESULTS: The TNF-alpha -308G/A AA genotype was associated with increased CP risk
      in Asians, non-smoking Asians and Caucasians, and this polymorphism was
      significantly associated with elevated risk of AgP in Asians and Caucasians.
      Asian individuals carrying AA genotype had a significantly increased risk for 
      863C/A. No significant association was identified between TNF -238G/A
      polymorphism and CP. CONCLUSIONS: These findings supported that TNF-alpha -308G/A
      and -863C/A polymorphisms may contribute to the susceptibility of periodontitis.

PMID- 24905366
TI  - Retirement: for better or worse?

PMID- 24905367
TI  - The moral heritage of the corner drugstore.

PMID- 24905368
TI  - Identifying and managing psychiatric emergencies.

PMID- 24905369
TI  - Delirium: presentation, epidemiology, and diagnostic evaluation (part 1).
AB  - Delirium is a highly prevalent and complex neuro- psychiatric disorder marked by
      attentional dysfunction, disturbances in multiple cognitive domains, and changes
      in motor behavior, perception, sleep, and thought process. Delirium results from
      diverse toxic, metabolic, infectious, and structural etiologies and is associated
      with a number of adverse outcomes. Delirium pathophysiology involves perturbation
      of multiple neurotransmitter systems. Behavioral presentations of delirium are
      common and are often misattributed to primary psychiatric processes. Diagnostic
      assessment of delirium includes thorough physical examination, careful cognitive
      testing, appropriate metabolic and infectious studies, review of medications, and
      structural brain imaging and electroencephalography as indicated. Pharmacologic
      and non-pharmacologic interventions have been documented to reduce the incidence
      and severity of delirium. Anti- psychotics are the treatment of choice for
      delirium-related agitation and psychosis.

PMID- 24905370
TI  - Delirium: treatment and prevention (part 2).
AB  - Delirium management begins with non-pharmacologic interventions and treatment of
      the underlying causes. There are no FDA-approved medications for delirium-related
      psychosis and agitation, although numerous agents have been studied. Small sample
      size, narrow inclusion criteria, lack of placebo controls and variable
      methodologies limit the generalizability of findings to date. Studies and expert
      guidelines support the use of antipsychotics for delirium-related psychosis and
      agitation, and demonstrate comparable efficacy and safety between first- and
      second- generation agents. Mounting evidence also suggests that antipsychotics
      and dexmedetomidine are effective in preventing delirium in surgical and
      mechanically- ventilated patients, respectively.

PMID- 24905371
TI  - The 'problem patient': modest advice for frustrated clinicians.
AB  - "Problem patients" are rare, but they take up a disproportionate amount of
      clinician time and energy. They often are defined in terms of the effect they
      have on clinicians rather than any specific behavior - such effects can include
      frustration, self-doubt and unprofessional behavior. The key to avoiding those
      pitfalls is to take a deeper look and understand what is behind patients'
      problematic behaviors. Given the vagueness of the term there are many potential
      etiologies, most of which are addressable, at least in part. This article
      presents a brief guide to identifying and managing the various conditions that
      can cause a disruption of the usually rewarding doctor-patient relationship, and
      also encourages us to consider the role we might play in this disruption.

PMID- 24905372
TI  - Serotonin syndrome: a concise review of a toxic state.
AB  - The serotonin syndrome is a toxic state caused by increased intrasynaptic
      serotonin and characterized by a triad of altered mental status, autonomic
      instability and neuromuscular abnormalities. It can result from exposure to a
      single serotonergic agent but is more likely to be due to polypharmacy, often
      with drugs from multiple classes. It develops over a short period of time and
      resolves just as quickly once identified and treated. Diagnostic criteria have
      been developed to assist in clinical practice. Treatment is largely supportive
      and prognosis is generally very favorable. Pharmacologic vigilance and prevention
      are key.

PMID- 24905373
TI  - Practical management of Alzheimer's dementia.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the elderly.
      There currently is no effective treatment that delays the onset or slows the
      progression of AD. Significant advances in neuroscience, genetics and molecular
      biology over the past 25 years have changed the way we think about AD. This
      article reviews the literature on diagnosis and treatment of AD so that primary
      care physicians can manage this complex disease.

PMID- 24905374
TI  - Emerging drugs of abuse: clinical and legal considerations.
AB  - Over the past several decades, nontraditional drugs of abuse, including bath
      salts, synthetic cannabinoids, and salvia, have increased in popularity and use.
      Despite this fact, they remain unfamiliar to many healthcare providers. Commonly
      marketed as "legal highs," these substances are being used for their desired
      neuropsychiatric effects, taking advantage of their accessibility, low cost,
      variable legality, and limited detection on traditional urine drug screens.
      Similar to traditional drugs of abuse, these substances have varying degrees of
      toxicity and may lead to potentially adverse effects, ranging from benign to life
      threatening. This paper offers a review of three of the more widely-used emerging
      drugs (or classes of drugs): bath salts, synthetic cannabinoids, and salvia. For
      each we review its history and development, the neurochemical basis for its
      clinical effects, the nature and route of ingestion, the range of desired
      effects, potential toxicities, diagnostic and therapeutic approaches, as well as
      social and legal considerations. [Full text available at
      http://rimed.org/rimedicaljournal-2014-06.asp, free with no login]. 

PMID- 24905375
TI  - Outpatient, awake, ultra-minimally invasive endoscopic treatment of lumbar disc
      herniations.
AB  - BACKGROUND: Endoscopic discectomy is an ultra- minimally invasive outpatient
      surgical option for the treatment of lumbar herniated discs. The purpose of this
      study was to assess the benefit of tranforaminal versus interlaminar endoscopic
      discectomy in patients with single level Lumbar 5-Sacral 1(L5-S1) disc
      herniations and lumbar radiculopathy. METHODS: After Institutional Review Board
      Approval, charts from 41 consecutive patients with complaints of lower back and
      radicular pain and an L5-S1 herniated disc who underwent an endoscopic procedure
      between 2007 and 2012 were reviewed. The transforaminal approach was used for
      patients with far lateral, foraminal, and paracentral disc herniations and the
      intralaminar approach was used for herniations that were more central. RESULTS:
      The average pain relief 1-year postoperatively was 75.9% for the transforaminal
      group and 75.3% for the interlaminar group, both excellent results as defined by
      MacNab. The average preoperative visual analogue scale (VAS) scores were 8.2 and
      8.4 for the transforaminal and interlaminar groups respectively, indicated in our
      questionnaire as severe and constant pain. The average 1-year postoperative VAS
      scores were 1.7 and 2.1, indicated in our questionnaire as mild and intermittent
      pain. There were no complications in the series of patients treated. CONCLUSIONS:
      The 1-year follow-up data presented here for transforaminal and intralaminar
      approaches to L5-S1 disc herniations appears to indicate that either approach can
      be used as determined to best suit the pathology without sacrificing the
      probability of postoperative pain improvement.

PMID- 24905376
TI  - Promoting medical student research productivity: the student perspective.
AB  - One-third of medical students complete medical school without significant
      exposure to research. This gap in their medical education is significant:
      research not only exposes medical students to scientific methodology and academic
      writing, but also encourages them to multi-task, communicate, and critically
      analyze the scientific literature - valuable skills that will serve them well in
      their future medical careers. We report herein the proceedings from a student-led
      symposium that aimed to promote student involvement in research at the Alpert
      Medical School of Brown University by providing practical information on how to
      successfully complete a research project.

PMID- 24905377
TI  - Gastrointestinal CMV in an elderly, immunocompetent patient.
AB  - An 83-year-old male with a history of diabetes but with an otherwise intact
      immune system presented with melena. Upper endoscopy showed gastric and duodenal
      ulcers. Colonoscopy showed colonic ulcers. Biopsies revealed cytomegalovirus
      (CMV). Therapy with an antiviral such as ganciclovir should be considered even in
      an immunocompetent patient if male and over the age of 55, or if they have
      chronic diseases such as diabetes or chronic kidney disease.

PMID- 24905378
TI  - An unusual case of pulmonary embolism in a young healthy female competitive
      rower.
AB  - Young healthy women without a genetic predisposition are considered to be at low
      risk for deep vein thrombosis and pulmonary emboli. We present an unusual case of
      pulmonary embolism in a 21-year-old female competitive rower likely caused by
      oral contraception and trauma of the axillary-subclavian vein by extrinsic
      compression due to repetitive arm movements.

PMID- 24905379
TI  - Rhode Island Clostridium difficile infection trends and laboratory ID events
      ranking.

PMID- 24905380
TI  - Using the Rhode Island Prescription Drug Monitoring Program (PMP).

PMID- 24905381
TI  - Enhanced surveillance for opioid overdose in Rhode Island.

PMID- 24905382
TI  - Do antiparasitic medicines used in aquaculture pose a risk to the Norwegian
      aquatic environment?
AB  - Aquaculture production is an important industry in many countries and there has
      been a growth in the use of medicines to ensure the health and cost effectiveness
      of the industry. This study focused on the inputs of sea lice medication to the
      marine environment. Diflubenzuron, teflubenzuron, emamectin benzoate,
      cypermethrin, and deltamethrin were measured in water, sediment, and biota
      samples in the vicinity of five aquaculture locations along the Norwegian coast.
      Deltamethrin and cypermethrin were not detected above the limits of detection in
      any samples. Diflubenzuron, teflubenzuron, and emamectin benzoate were detected,
      and the data was compared the UK Environmental Quality Standards. The
      concentrations of emamectin benzoate detected in sediments exceed the
      environmental quality standard (EQS) on 5 occasions in this study. The EQS for
      teflubenzuron in sediment was exceeded in 67% of the samples and exceeded for
      diflubenzuron in 40% of the water samples collected. A crude assessment of the
      concentrations detected in the shrimp collected from one location and the levels
      at which chronic effects are seen in shrimp would suggest that there is a
      potential risk to shrimp. It would also be reasonable to extrapolate this to any
      species that undergoes moulting during its life cycle. 

PMID- 24905383
TI  - Shock wave study of the thermal dissociations of C3F6 and c-C3F6. I. dissociation
      of hexafluoropropene.
AB  - The thermal dissociation of C3F6 was studied between 1330 and 2210 K in shock
      waves monitoring the UV absorption of CF2. CF2 yields of about 2.6 per parent
      C3F6 were obtained at reactant concentrations of 500-1000 ppm in the bath gas Ar.
      These yields dropped to about 1.8 when reactant concentrations were lowered to 60
      ppm. The increase of the CF2 yield with increasing concentration was attributed
      to bimolecular reactions between primary and secondary dissociation products.
      Quantum-chemical and kinetic modeling calculations helped to estimate the
      contributions from the various primary dissociation steps. It was shown that the
      measurements correspond to unimolecular reactions in their falloff range. Falloff
      representations of the rate constants are given, leading to an overall high
      pressure rate constant kinfinity = 2.0 * 10(17)(-104 kcal mol(-1)/RT) s(-1) and a
      relative rate of about 2/3:1/3 for the reactions C3F6 -> CF3CF + CF2 versus C3F6 
      > C2F3 + CF3. 

PMID- 24905384
TI  - Local gene silencing in plants via synthetic dsRNA and carrier peptide.
AB  - Quick and facile transient RNA interference (RNAi) is one of the most valuable
      plant biotechnologies for analysing plant gene functions. To establish a novel
      double-strand RNA (dsRNA) delivery system for plants, we developed an ionic
      complex of synthetic dsRNA with a carrier peptide in which a cell-penetrating
      peptide is fused with a polycation sequence as a gene carrier. The dsRNA-peptide
      complex is 100-300 nm in diameter and positively charged. Infiltration of the
      complex into intact leaf cells of Arabidopsis thaliana successfully induced rapid
      and efficient down-regulation of exogenous and endogenous genes such as yellow
      fluorescent protein and chalcone synthase. The present method realizes quick and
      local gene silencing in specific tissues and/or organs in plants. 

PMID- 24905385
TI  - Intranasal administration of a combination of choline chloride, vitamin C, and
      selenium attenuates the allergic effect in a mouse model of airway disease.
AB  - Respiratory allergic disease is an inflammatory condition accompanied by
      oxidative stress. Supplementation of an anti-inflammatory agent with antioxidants
      may have a therapeutic effect. In this study, the effects of choline chloride in
      combination with antioxidants were evaluated via the intranasal route in a mouse
      model of allergic airway disease. Balb/c mice were sensitized on days 0, 7, and
      14 and challenged on days 25-30 with cockroach extract (CE) and with a booster
      challenge on day 38. They were treated with choline chloride (ChCl; 1mg/kg),
      vitamin C (Vit C; 308.33 mg/kg), and selenium (Se; 1mg/kg) alone or in
      combination via the intranasal route on days 31, 33, 35, 37, and 39. The mice
      were sacrificed on day 40 to collect blood, bronchoalveolar lavage fluid, lungs,
      and spleen. Mice immunized with CE showed a significant increase in airway
      hyperresponsiveness (AHR), lung inflammation, Th2 cytokines, and the oxidative
      stress markers intracellular reactive oxygen species and 8-isoprostanes compared
      to the phosphate-buffered saline control group. A significant decrease was
      observed in these parameters with all the treatments (p<0.01). The highest
      decrease was noticed in the ChCl+Vit C+Se-treated group, with AHR decreased to
      the normal level. This group also showed the highest decrease in airway
      inflammation (p<0.001), IL-4 and IL-5 (p<0.001), IgE and IgG1 (p<0.001), NF
      kappaB (p<0.001), and 8-isoprostane levels (p<0.001). Glutathione peroxidase
      activity, which was decreased significantly in CE-immunized mice, was restored to
      normal levels in this group (p<0.001). IL-10 level was decreased in CE-immunized
      mice and was restored to normal by combination treatment. The combination
      treatment induced FOXP3(+) cells in splenocyte culture, responsible for the
      upregulation of IL-10. In conclusion, the combination of choline chloride,
      vitamin C, and selenium via the intranasal route reduces AHR, inflammation, and
      oxidative stress, probably by causing IL-10 production by FOXP3(+) cells, and
      possesses therapeutic potential against allergic airway disease.

PMID- 24905386
TI  - Rare hemoglobin variants in Tunisian population.
AB  - During the last 30 years, many studies concerning hemoglobinopathies were
      realized among Tunisians. More than twenty different thalassemic alleles were
      detected on the beta-globin gene, and less are affecting the alpha-globin genes.
      Unusual hemoglobin (Hb) variants other than Hb S, Hb C, and Hb O-arab, which are
      the most frequent variants in Tunisia, were also detected. Eight Tunisian
      subjects were studied at phenotypic and molecular levels. Hematological indices
      and hemoglobin (Hb) pattern were performed by alkaline electrophoresis and
      isoelectric focusing (IEF),and the Hb fractions were quantitated by cation
      exchange HPLC. On genomic level, coding regions were amplified by polymerase
      chain reaction (PCR) followed by a sequencing of the purified PCR products using
      the dye terminator method. Seven uncommon Hb variants were detected and described
      for the first time among Tunisians. HbA2-Tunis [delta46(CD5), Gly -> Glu, GGG ->
      GAG] is the newly described delta-chain variant in our laboratory, and some other
      variants (Hb Constant Spring, G San Jose, and Hb J-Bangkok) are very uncommon in
      the Mediterranean region. We present here an updated review of the Hb variants
      detected among Tunisians. Twenty-one rare Hb variants were detected affecting the
      alpha1-, alpha2-, delta-, gamma-, and beta-globin genes, leading in some cases to
      a severe phenotype especially when the stability is completely altered. The
      ethnical history of Tunisia could explain this important variability of the
      observed rare Hb variants. 

PMID- 24905387
TI  - The magic of collective emotional intelligence in learning groups: No guys needed
      for the spell!
AB  - Using a cross-lagged design, the present study tests an integrative model of
      emergent collective emotions in learning groups. Our results indicate that the
      percentage of women in the group fosters the emergence of collective emotional
      intelligence, which in turn stimulates social integration within groups
      (increases group cohesion and reduces relationship conflict) and the associated
      affective similarity, with beneficial effects for group effectiveness.

PMID- 24905388
TI  - Hypermobility accelerates adjacent-segment disease after ACDF?

PMID- 24905389
TI  - Iatrogenic cerebrospinal fluid leak and intracranial hypotension after
      gynecological surgery.
AB  - Perineural cysts are common lesions of the sacral spine. They have rarely been
      reported in a presacral location, leading to their misdiagnosis as a
      gynecological lesion. The authors report the second such case, in a patient
      undergoing fenestration of what was presumed to be a benign pelvic cyst, and the
      resultant high-flow CSF leak that occurred. They describe the clinical
      presentation and manifestations of intracranial hypotension, as well as the
      pertinent investigations. They also review the literature for the best management
      options for this condition. Although they are uncommon, large perineural cysts
      should be included in the differential diagnosis when examining patients with a
      pelvic lesion. Appropriate imaging investigations should be performed to rule out
      a perineural cyst. The CSF leak that occurs from iatrogenic cyst fenestration may
      not respond to traditional first-line treatments for intracranial hypotension and
      may require early surgical intervention. The authors would recommend
      neurosurgical involvement prior to definitive treatment. 

PMID- 24905391
TI  - Validating the Thoracolumbar Injury Classification and Severity Score.

PMID- 24905390
TI  - Molecular characterization of chordoma xenografts generated from a novel primary
      chordoma cell source and two chordoma cell lines.
AB  - OBJECT: Chordoma cells can generate solid-like tumors in xenograft models that
      express some molecular characteristics of the parent tumor, including positivity
      for brachyury and cytokeratins. However, there is a dearth of molecular markers
      that relate to chordoma tumor growth, as well as the cell lines needed to advance
      treatment. The objective in this study was to isolate a novel primary chordoma
      cell source and analyze the characteristics of tumor growth in a mouse xenograft
      model for comparison with the established U-CH1 and U-CH2b cell lines. METHODS:
      Primary cells from a sacral chordoma, called "DVC-4," were cultured alongside U
      CH1 and U-CH2b cells for more than 20 passages and characterized for expression
      of CD24 and brachyury. While brachyury is believed essential for driving tumor
      formation, CD24 is associated with healthy nucleus pulposus cells. Each cell type
      was subcutaneously implanted in NOD/SCID/IL2Rgamma(null) mice. The percentage of
      solid tumors formed, time to maximum tumor size, and immunostaining scores for
      CD24 and brachyury (intensity scores of 0-3, heterogeneity scores of 0-1) were
      reported and evaluated to test differences across groups. RESULTS: The DVC-4
      cells retained chordoma-like morphology in culture and exhibited CD24 and
      brachyury expression profiles in vitro that were similar to those for U-CH1 and U
      CH2b. Both U-CH1 and DVC-4 cells grew tumors at rates that were faster than those
      for U-CH2b cells. Gross tumor developed at nearly every site (95%) injected with
      U-CH1 and at most sites (75%) injected with DVC-4. In contrast, U-CH2b cells
      produced grossly visible tumors in less than 50% of injected sites. Brachyury
      staining was similar among tumors derived from all 3 cell types and was intensely
      positive (scores of 2-3) in a majority of tissue sections. In contrast,
      differences in the pattern and intensity of staining for CD24 were noted among
      the 3 types of cell-derived tumors (p < 0.05, chi-square test), with evidence of
      intense and uniform staining in a majority of U-CH1 tumor sections (score of 3)
      and more than half of the DVC-4 tumor sections (scores of 2-3). In contrast, a
      majority of sections from U-CH2b cells stained modestly for CD24 (scores of 1-2)
      with a predominantly heterogeneous staining pattern. CONCLUSIONS: This is the
      first report on xenografts generated from U-CH2b cells in which a low
      tumorigenicity was discovered despite evidence of chordoma-like characteristics
      in vitro. For tumors derived from a primary chordoma cell and U-CH1 cell line,
      similarly intense staining for CD24 was observed, which may correspond to their
      similar potential to grow tumors. In contrast, U-CH2b tumors stained less
      intensely for CD24. These results emphasize that many markers, including CD24,
      may be useful in distinguishing among chordoma cell types and their
      tumorigenicity in vivo.

PMID- 24905392
TI  - Estimating EQ-5D values from the Neck Disability Index and numeric rating scales
      for neck and arm pain.
AB  - OBJECT: The Neck Disability Index (NDI) and numeric rating scales (0 to 10) for
      neck pain and arm pain are widely used cervical spine disease-specific measures.
      Recent studies have shown that there is a strong relationship between the SF-6D
      and the NDI such that using a simple linear regression allows for the estimation
      of an SF-6D value from the NDI alone. Due to ease of administration and scoring,
      the EQ-5D is increasingly being used as a measure of utility in the clinical
      setting. The purpose of this study is to determine if the EQ-5D values can be
      estimated from commonly available cervical spine disease-specific health-related
      quality of life measures, much like the SF-6D. METHODS: The EQ-5D, NDI, neck pain
      score, and arm pain score were prospectively collected in 3732 patients who
      presented to the authors' clinic with degenerative cervical spine disorders.
      Correlation coefficients for paired observations from multiple time points
      between the NDI, neck pain and arm pain scores, and EQ-5D were determined.
      Regression models were built to estimate the EQ-5D values from the NDI, neck
      pain, and arm pain scores. RESULTS: The mean age of the 3732 patients was 53.3 +/
      12.2 years, and 43% were male. Correlations between the EQ-5D and the NDI, neck
      pain score, and arm pain score were statistically significant (p < 0.0001), with
      correlation coefficients of -0.77, -0.62, and -0.50, respectively. The regression
      equation 0.98947 + (-0.00705 * NDI) + (-0.00875 * arm pain score) + (-0.00877 *
      neck pain score) to predict EQ-5D had an R-square of 0.62 and a root mean square
      error (RMSE) of 0.146. The model using NDI alone had an R-square of 0.59 and a
      RMSE of 0.150. The model using the individual NDI items had an R-square of 0.46
      and an RMSE of 0.172. The correlation coefficient between the observed and
      estimated EQ-5D scores was 0.79. There was no statistically significant
      difference between the actual EQ-5D score (0.603 +/- 0.235) and the estimated EQ
      5D score (0.603 +/- 0.185) using the NDI, neck pain score, and arm pain score
      regression model. However, rounding off the coefficients to fewer than 5 decimal
      places produced less accurate results. CONCLUSIONS: The regression model
      estimating the EQ-5D from the NDI, neck pain score, and arm pain score accounted
      for 60% of the variability of the EQ-5D with a relatively large RMSE. This
      regression model may not be sufficient to accurately or reliably estimate actual
      EQ-5D values.

PMID- 24905393
TI  - Subacute posttraumatic ascending myelopathy in a 15-year-old boy.
AB  - Secondary injury following initial spinal cord trauma is uncommon and frequently
      attributed to mismanagement of an unprotected cord in the acute time period after
      injury. Subacute posttraumatic ascending myelopathy (SPAM) is a rare occurrence
      in the days to weeks following an initial spinal cord injury that is unrelated to
      manipulation of an unprotected cord and involves 4 or more vertebral levels above
      the original injury. The authors present a case of SPAM occurring in a 15-year
      old boy who sustained a T3-4 fracture-dislocation resulting in a complete spinal
      cord injury, and they highlight the imaging findings and optimum treatment for
      this rare event. 

PMID- 24905395
TI  - Tumor extravasation following a cement augmentation procedure for vertebral
      compression fracture in metastatic spinal disease.
AB  - Balloon kyphoplasty (BKP) has been proven to be safe and effective in the
      management of pathological vertebral compression fracture (VCF) due to metastatic
      spinal disease. The most common serious complications related to BKP include
      cement extravasation and new fractures at adjacent levels. Although the potential
      for "tumor extravasation" has been discussed as a potential iatrogenic
      complication, it has yet to be confirmed. The authors report on 2 cases of tumor
      extravasation following BKP, which they base on an observed unusual rapid tumor
      spread pattern into the adjacent tissues. They postulate that by increasing the
      vertebral body internal pressure and disrupting the tissues during balloon
      inflation and cement application, a soft-tissue tumor can be forced beyond the
      vertebral bony boundaries through pathological cortical defects. This phenomenon
      can manifest radiologically as subligamentous spread and/or extension into venous
      sinusoids, resulting in epidural venous plexus involvement, with subsequent tumor
      migration into the adjacent vertebral segments. Accordingly, the authors advise
      caution in using BKP when significant epidural tumor is present. The complication
      they encountered has caused them to modify their preference such that they now
      first use radiosurgery and subsequently BKP to ensure the target is appropriately
      treated, and they are currently developing possible modifications of procedural
      technique to reduce the risk. 

PMID- 24905394
TI  - Teriparatide increases the insertional torque of pedicle screws during fusion
      surgery in patients with postmenopausal osteoporosis.
AB  - OBJECT: The object of this study was to examine the efficacy of preoperative
      teriparatide treatment for increasing the insertional torque of pedicle screws
      during fusion surgery in postmenopausal women with osteoporosis. METHODS: Fusion
      surgery for the thoracic and/or lumbar spine was performed in 29 postmenopausal
      women with osteoporosis aged 65-82 years (mean 72.2 years). The patients were
      divided into 2 groups based on whether they were treated with teriparatide (n =
      13) or not (n = 16) before the surgery. In the teriparatide-treated group,
      patients received preoperative teriparatide therapy as either a daily (20
      MUg/day, n = 7) or a weekly (56.5 MUg/week, n = 6) injection for a mean of 61.4
      days and a minimum of 31 days. During surgery, the insertional torque was
      measured in 212 screws inserted from T-7 to L-5 and compared between the 2
      groups. The correlation between the insertional torque and the duration of
      preoperative teriparatide treatment was also investigated. RESULTS: The mean
      insertional torque value in the teriparatide group was 1.28 +/- 0.42 Nm, which
      was significantly higher than in the control group (1.08 +/- 0.52 Nm, p < 0.01).
      There was no significant difference between the daily and the weekly teriparatide
      groups with respect to mean insertional torque value (1.34 +/- 0.50 Nm and 1.18
      +/- 0.43 Nm, respectively, p = 0.07). There was negligible correlation between
      insertional torque and duration of preoperative teriparatide treatment (r(2) =
      0.05, p < 0.01). CONCLUSIONS: Teriparatide injections beginning at least 1 month
      prior to surgery were effective in increasing the insertional torque of pedicle
      screws during surgery in patients with postmenopausal osteoporosis. Preoperative
      teriparatide treatment might be an option for maximizing the purchase of the
      pedicle screws to the bone at the time of fusion surgery.

PMID- 24905396
TI  - A step-up test procedure to find the minimum effective dose.
AB  - It is of great interest to find the minimum effective dose (MED) in dose-response
      studies. A sequence of decreasing null hypotheses to find the MED is formulated
      under the assumption of nondecreasing dose response means. A step-up multiple
      test procedure that controls the familywise error rate (FWER) is constructed
      based on the maximum likelihood estimators for the monotone normal means. When
      the MED is equal to one, the proposed test is uniformly more powerful than Hsu
      and Berger's test (1999). Also, a simulation study shows a substantial power
      improvement for the proposed test over four competitors. Three R-codes are
      provided in Supplemental Materials for this article. Go to the publishers online
      edition of Journal of Biopharmaceutical Statistics to view the files. 

PMID- 24905397
TI  - Existential behavioral therapy for informal caregivers of palliative patients:
      barriers and promoters of support utilization.
AB  - OBJECTIVE: Several interventions have been developed during recent years to
      support informal caregivers of palliative patients. However, these trials
      reported low enrollment rates. Employing a newly developed group intervention,
      existential behavioral therapy (EBT), one study reported that only 13.6% of
      approached informal caregivers participated. The purpose of our present study was
      to identify the reasons for this low enrollment rate in order to improve future
      support designs. METHOD: All participants in the EBT trial (intervention vs.
      standard-care control group) as well as those who declined participation during a
      4-month recruitment period were studied prospectively over 12 months. Andersen's
      behavioral model of healthcare service use was employed to identify group
      differences between acceptors and decliners: predisposing (age, gender,
      education, family status, relationship), enabling (social support, distance to
      hospital, caring vs. bereaved), and need factors (psychological distress, quality
      of life) were evaluated in a binary-logistic model. RESULTS: Some 94 decliners
      were compared to 160 EBT participants (n = 81 intervention, n = 79 control).
      Caregivers who took part were significantly more distressed and suffered from a
      lower quality of life compared to decliners. Not only these need factors but also
      predisposing (age <55 years) and enabling (use of social/professional support,
      familiarity with caregiving institution) factors were associated with EBT
      utilization. At the 12-month follow-up, EBT intervention participants reported
      greater quality of life improvements than decliners or controls (p = 0.05). While
      all groups had mean anxiety scores below the cutoff at 12-month follow-up,
      decliners showed better improvement in anxiety compared to EBT participants
      (intervention p = 0.04, controls p = 0.03). SIGNIFICANCE OF RESULTS: On average,
      decliners are less burdened: they may be more resilient, may have better coping
      strategies, or already have a sufficient support network in place. Screening
      caregivers with regard to their experienced quality of life and targeting those
      in need, especially younger caregivers with low levels of quality of life, may
      help to allocate resources more appropriately.

PMID- 24905398
TI  - A distinct role of pectate lyases in the formation of feeding structures induced
      by cyst and root-knot nematodes.
AB  - Pectin in the primary plant cell wall is thought to be responsible for its
      porosity, charge density, and microfibril spacing and is the main component of
      the middle lamella. Plant-parasitic nematodes secrete cell wall-degrading enzymes
      that macerate the plant tissue, facilitating the penetration and migration within
      the roots. In sedentary endoparasitic nematodes, these enzymes are released only
      during the migration of infective juveniles through the root. Later, nematodes
      manipulate the expression of host plant genes, including various cell wall
      enzymes, in order to induce specific feeding sites. In this study, we
      investigated expression of two Arabidopsis pectate lyase-like genes (PLL), PLL18
      (At3g27400) and PLL19 (At4g24780), together with pectic epitopes with different
      degrees of methylesterification in both syncytia induced by the cyst nematode
      Heterodera schachtii and giant cells induced by the root-knot nematode
      Meloidogyne incognita. We confirmed upregulation of PLL18 and PLL19 in both types
      of feeding sites with quantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR) and in situ RT-PCR. Furthermore, the functional analysis of
      mutants demonstrated the important role of both PLL genes in the development and
      maintenance of syncytia but not giant cells. Our results show that both enzymes
      play distinct roles in different infected root tissues as well as during
      parasitism of different nematodes. 

PMID- 24905399
TI  - Transferrin targeted core-shell nanomedicine for combinatorial delivery of
      doxorubicin and sorafenib against hepatocellular carcinoma.
AB  - Combinatorial drug delivery is an attractive, but challenging requirement of next
      generation cancer nanomedicines. Here, we report a transferrin-targeted core
      shell nanomedicine formed by encapsulating two clinically used single-agent
      drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in
      poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by
      a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell
      inhibited aberrant oncogenic signaling involved in cell proliferation,
      doxorubicin from the nano-core evoked DNA intercalation thereby killing >75% of
      cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed
      enhanced cellular uptake and synergistic cytotoxicity in ~92% of cells,
      particularly in iron-deficient microenvironment. Studies using 3D spheroids of
      liver tumor indicated efficient penetration of targeted core-shell nanoparticles
      throughout the tissue causing uniform cell killing. Thus, we show that rationally
      designed core-shell nanoparticles can effectively combine clinically relevant
      single-agent drugs for exerting synergistic activity against liver cancer. FROM
      THE CLINICAL EDITOR: Transferrin-targeted core-shell nanomedicine encapsulating
      doxorubicin and sorafenib was studied as a drug delivery system against
      hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic
      effects, paving the way towards potential future clinical applications of similar
      techniques.

PMID- 24905400
TI  - Preclinical development and ocular biodistribution of gemini-DNA nanoparticles
      after intravitreal and topical administration: towards non-invasive glaucoma gene
      therapy.
AB  - Gene therapy could offer improvement in the treatment of glaucoma compared to the
      current standard of lowering intraocular pressure. We have developed and
      characterized non-viral gemini surfactant-phospholipid nanoparticles (GL-NPs) for
      intravitreal and topical administration. Optimized GL-NPs (size range 150-180 nm)
      were biocompatible with rat retinal ganglion (RGC-5) cells with >95% viability by
      PrestoBlueTM assay. GL-NPs carrying Cy5-labeled plasmid DNA demonstrated distinct
      trafficking behavior and biodisposition within the eye in vivo after intravitreal
      or topical application with respect to pathways of movement and physicochemical
      stability. After intravitreal injection in mice, GL-NPs localized within the
      nerve fiber layer of the retina, whereas after topical application, GL-NPs were
      located in several anterior chamber tissues, including the limbus, iris and
      conjunctiva. GL-NPs were thermodynamically stable in the vitreous and tear fluid
      and were trafficked as single, non-aggregated particles after both types of
      administration. FROM THE CLINICAL EDITOR: In this paper, the development and
      characterization of non-viral gemini surfactant-phospholipid nanoparticles is
      reported with the goal of establishing a gene delivery system that addresses
      glaucoma in a non-invasive fashion. The authors found that after topical
      application, the concentration of these nanoparticles was higher in anterior
      chamber-related components of the eye, whereas intra-vitreal administration
      resulted in accumulation in the retinal nerve fibre layer.

PMID- 24905401
TI  - Monitoring the formation of carbide crystal phases during the thermal
      decomposition of 3d transition metal dicarboxylate complexes.
AB  - Single molecule precursors can help to simplify the synthesis of complex alloys
      by minimizing the amount of necessary starting reagents. However, single molecule
      precursors are time consuming to prepare with very few being commercially
      available. In this study, a simple precipitation method is used to prepare Fe,
      Co, and Ni fumarate and succinate complexes. These complexes were then thermally
      decomposed in an inert atmosphere to test their efficiency as single molecule
      precursors for the formation of metal carbide phases. Elevated temperature X-ray
      diffraction was used to identify the crystal phases produced upon decomposition
      of the metal dicarboxylate complexes. Thermogravimetric analysis coupled with an
      infrared detector was used to identify the developed gaseous decomposition
      products. All complexes tested showed a reduction from the starting M(2+)
      oxidation state to the M(0) oxidation state, upon decomposition. Also, each
      complex tested showed CO2 and H2O as gaseous decomposition products. Nickel
      succinate, iron succinate, and iron fumarate complexes were found to form carbide
      phases upon decomposition. This proves that transition metal dicarboxylate salts
      can be employed as efficient single molecule precursors for the formation of
      metal carbide crystal phases. 

PMID- 24905402
TI  - Variation in general practice prostate-specific antigen testing and prostate
      cancer outcomes: an ecological study.
AB  - Knowledge is sparse about the consequences of variation in prostate-specific
      antigen (PSA) testing rates in general practice. This study investigated
      associations between PSA testing and prostate cancer- related outcomes in Danish
      general practice, where screening for prostate cancer is not recommended.
      National registers were used to divide general practices into four groups based
      on their adjusted PSA test rate 2004-2009. We analysed associations between PSA
      test rate and prostate cancer-related outcomes using Poisson regression adjusted
      for potential confounders. We included 368 general practices, 303,098 men and
      4,199 incident prostate cancers. Men in the highest testing quartile of practices
      compared to men in the lowest quartile had increased risk of trans-rectal
      ultrasound (incidence rate ratio (IRR): 1.20, 95% CI, 0.95-1.51), biopsy (IRR:
      1.76, 95% CI, 1.54-2.02), and getting a prostate cancer diagnosis (IRR: 1.37, 95%
      CI, 1.23-1.52). More were diagnosed with local stage disease (IRR: 1.61, 95% CI,
      1.37-1.89) with no differences regarding regional or distant stage. The IRR for
      prostatectomy was 2.25 (95% CI, 1.72-2.94) and 1.28 (95% CI, 1.02-1.62) for
      radiotherapy. No differences in prostate cancer or overall mortality were found
      between the groups. These results show that the highest PSA testing general
      practices may not reduce prostate cancer mortality but increase the downstream
      use of diagnostic and surgical procedures with potentially harmful side effects. 

PMID- 24905403
TI  - Prospective study to investigate the use of fine needle aspiration techniques in
      UK veterinary practice.
AB  - OBJECTIVES: To document the fine needle aspiration methods used by UK veterinary
      practitioners for the assessment of cutaneous masses and relate this to the
      achievement of a representative sample. METHODS: An internet-based questionnaire
      was designed and publicised in the UK national veterinary press, at a national
      surgical meeting, and in letters to veterinary surgeons. RESULTS: One hundred and
      seventy respondents replied to the questionnaire: 58 . 2% sampled cutaneous
      masses on the basis of appearance or behaviour; 41 . 3% sampled every cutaneous
      mass. Practitioners with a greater oncological caseload or who graduated more
      recently were more likely to recommend fine needle aspiration for every cutaneous
      mass (P = 0 . 019 and P = 0 . 0002 respectively); 66 . 5% of respondents applied
      suction during fine needle aspiration; 89% of all respondents used a 2 or 5 mL
      syringe in combination with a 21 or 23 G needle. There was no statistically
      significant association between achievement of a representative sample and
      syringe (P = 0 . 64) or needle size (P = 0 . 63). CLINICAL SIGNIFICANCE: Fine
      needle aspiration is widely used in UK practice, but may be underutilised in
      practices with lower oncological caseloads. Survey participants reported a high
      rate of representative samples obtained using all the commonly used techniques.
      Further work is required to confirm these observations.

PMID- 24905405
TI  - Genetic variation of the endangered Gentiana lutea L. var. aurantiaca
      (Gentianaceae) in populations from the Northwest Iberian Peninsula.
AB  - Gentiana lutea L. (G. lutea L.) is an endangered plant, patchily distributed
      along the mountains of Central and Southern Europe. In this study, inter-simple
      sequence repeat (ISSR) markers were used to investigate the genetic variation in
      this species within and among populations of G. lutea L. var. aurantiaca of the
      Cantabrian Mountains (Northwest Iberian Peninsula). Samples of G. lutea L.
      collected at different locations of the Pyrenees and samples of G. lutea L.
      subsp. vardjanii of the Dolomites Alps were also analyzed for comparison. Using
      nine ISSR primers, 106 bands were generated, and 89.6% of those were polymorphic.
      The populations from the Northwest Iberian Peninsula were clustered in three
      different groups, with a significant correlation between genetic and geographic
      distances. Gentiana lutea L. var. aurantiaca showed 19.8% private loci and
      demonstrated a remarkable level of genetic variation, both among populations and
      within populations; those populations with the highest level of isolation show
      the lowest genetic variation within populations. The low number of individuals,
      as well as the observed genetic structure of the analyzed populations makes it
      necessary to protect them to ensure their survival before they are too small to
      persist naturally. 

PMID- 24905404
TI  - Cytotoxic autophagy in cancer therapy.
AB  - Autophagy is a process of cellular self-digestion, whereby the cell degrades
      subcellular materials in order to generate energy and metabolic precursors in
      order to prolong survival, classically under conditions of nutrient deprivation.
      Autophagy can also involve the degradation of damaged or aged organelles, and
      misfolded or damaged proteins to eliminate these components that might otherwise
      be deleterious to cellular survival. Consequently, autophagy has generally been
      considered a prosurvival response. Many, if not most chemotherapeutic drugs and
      radiation also promote autophagy, which is generally considered a cytoprotective
      response, in that its inhibition frequently promotes apoptotic cells death.
      Furthermore, it has been shown that conventional chemotherapeutic drugs and
      radiation alone rarely induce a form of autophagy that leads to cell death.
      However, there are multiple examples in the literature where newer
      chemotherapeutic agents, drug combinations or drugs in combination with radiation
      promote autophagic cell death. This review will describe autophagic cell death
      induced in breast tumor cells, lung cancer cells as well as glioblastoma,
      demonstrating that it cannot be concluded that stress induced autophagy is, of
      necessity, cytoprotective in function. 

PMID- 24905406
TI  - Direct analysis of hCGbetacf glycosylation in normal and aberrant pregnancy by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - The analysis of human chorionic gonadotropin (hCG) in clinical chemistry
      laboratories by specific immunoassay is well established. However, changes in
      glycosylation are not as easily assayed and yet alterations in hCG glycosylation
      is associated with abnormal pregnancy. hCGbeta-core fragment (hCGbetacf) was
      isolated from the urine of women, pregnant with normal, molar and hyperemesis
      gravidarum pregnancies. Each sample was subjected to matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) analysis
      following dithiothreitol (DTT) reduction and fingerprint spectra of peptide
      hCGbeta 6-40 were analyzed. Samples were variably glycosylated, where most
      structures were small, core and largely mono-antennary. Larger single bi
      antennary and mixtures of larger mono-antennary and bi-antennary moieties were
      also observed in some samples. Larger glycoforms were more abundant in the
      abnormal pregnancies and tri-antennary carbohydrate moieties were only observed
      in the samples from molar and hyperemesis gravidarum pregnancies. Given that such
      spectral profiling differences may be characteristic, development of small sample
      preparation for mass spectral analysis of hCG may lead to a simpler and faster
      approach to glycostructural analysis and potentially a novel clinical diagnostic
      test. 

PMID- 24905407
TI  - A comprehensive insight into tetracycline resistant bacteria and antibiotic
      resistance genes in activated sludge using next-generation sequencing.
AB  - In order to comprehensively investigate tetracycline resistance in activated
      sludge of sewage treatment plants, 454 pyrosequencing and Illumina high
      throughput sequencing were used to detect potential tetracycline resistant
      bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with
      different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene
      revealed that tetracycline treatment greatly affected the bacterial community
      structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas,
      Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus,
      Novosphingobium and Rhodobacter were identified as potential TRB in the sludge.
      Results of qPCR, molecular cloning and metagenomic analysis consistently
      indicated that tetracycline treatment could increase both the abundance and
      diversity of the tet genes, but decreased the occurrence and diversity of non
      tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis
      showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was
      found to pose greater effects on the bacterial community composition, which may
      be responsible for the variations of the ARGs abundance. This study indicated
      that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can
      be effectively used to explore ARB and ARGs in the environment, and future
      studies should include an in-depth investigation of the relationship between
      microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge.

PMID- 24905408
TI  - Systemic injection of low-dose lipopolysaccharide fails to break down the blood
      brain barrier or activate the TLR4-MyD88 pathway in neonatal rat brain.
AB  - We aimed to investigate whether peripheral low-dose lipopolysaccharide (LPS)
      induces the breakdown of the blood-brain barrier (BBB) and/or the activation of
      toll-like receptor 4 (TLR4) in the neonatal rat brain. Neonatal rats received
      intraperitoneal injections of low-dose LPS (0.3 mg/kg?bw), and the BBB compromise
      was detected by Evans Blue extravasation and electron microscopy. Meanwhile,
      TLR4, adaptin myeloid differentiation factor 88 (MyD88), nuclear transcription
      factor kappa-B (NF-kappaB) p50 and tumor necrosis factor alpha (TNFalpha) in the
      neonatal rat brain were determined by quantitative real-time polymerase chain
      reaction (PCR) and Western Blot. Immunohistochemistry was used to determine the
      distribution and activation of microglia in the brain after LPS administration.
      It was demonstrated that Evans Blue extravasation was not observed in the brain
      parenchyma, and that tight junctions of cerebral endothelial cells remained
      intact after systemic injections of LPS in neonatal rats. Although
      intracerebroventricular injections of LPS activated microglia and up-regulated
      the expression of TLR4, MyD88, NF-kappaB p50 and TNFalpha in the neonatal rat
      brain, systemic LPS did not induce these responses. These findings indicate that
      while the neonatal rat brain responds to the direct intra-cerebral administration
      of LPS through robust TLR4 activation, systemic low-dose LPS does not induce the
      innate immune reaction or compromise the BBB in neonatal rats. 

PMID- 24905409
TI  - The role of AhR in autoimmune regulation and its potential as a therapeutic
      target against CD4 T cell mediated inflammatory disorder.
AB  - AhR has recently emerged as a critical physiological regulator of immune
      responses affecting both innate and adaptive systems. Since the AhR signaling
      pathway represents an important link between environmental stimulators and immune
      mediated inflammatory disorder, it has become the object of great interest among
      researchers recently. The current review discusses new insights into the
      mechanisms of action of a select group of inflammatory autoimmune diseases and
      the ligand-activated AhR signaling pathway. Representative ligands of AhR, both
      exogenous and endogenous, are also reviewed relative to their potential use as
      tools for understanding the role of AhR and as potential therapeutics for the
      treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper
      T cells, which play important roles both in self-immune tolerance and in
      inflammatory autoimmune diseases. Evidence indicating the potential use of these
      ligands in regulating inflammation in various diseases is highlighted, and
      potential mechanisms of action causing immune system effects mediated by AhR
      signaling are also discussed. The current review will contribute to a better
      understanding of the role of AhR and its signaling pathway in CD4 helper T cell
      mediated inflammatory disorder. Considering the established importance of AhR in
      immune regulation and its potential as a therapeutic target, we also think that
      both further investigation into the molecular mechanisms of immune regulation
      that are mediated by the ligand-specific AhR signaling pathway, and integrated
      research and development of new therapeutic drug candidates targeting the AhR
      signaling pathway should be pursued urgently. 

PMID- 24905410
TI  - The effect of lithospermic acid, an antioxidant, on development of diabetic
      retinopathy in spontaneously obese diabetic rats.
AB  - BACKGROUND: Lithospermic acid B (LAB), an active component isolated from Salvia
      miltiorrhiza radix, has been reported to have antioxidant effects. We examined
      the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS AND
      FINDINGS: LAB (10 or 20 mg/kg) or normal saline were given orally once daily to
      24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic
      findings, vascular endothelial growth factor (VEGF) expression in the eyeball,
      VEGF levels in the ocular fluid, and any structural abnormalities in the retina
      were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive
      protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor
      alpha (TNFalpha) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were
      also measured. Treatment with LAB prevented vascular leakage and basement
      membrane thickening in retinal capillaries in a dose-dependent manner. Insulin
      resistance and glucose intolerance were significantly improved by LAB treatment.
      The levels of serum hsCRP, MCP1, TNFalpha, and urinary 8-OHdG were lower in the
      LAB-treated OLETF rats than in the controls. CONCLUSIONS: Treatment with LAB had
      a preventive effect on the development of diabetic retinopathy in this animal
      model, probably because of its antioxidative effects and anti-inflammatory
      effects.

PMID- 24905411
TI  - Limited evolution of inferred HIV-1 tropism while viremia is undetectable during
      standard HAART therapy.
AB  - BACKGROUND: HIV patients on suppressive antiretroviral therapy have undetectable
      viremia making it impossible to screen plasma HIV tropism if regimen change is
      required during suppression. We investigated the prevalence and predictors of
      tropism switch from CCR5-using ("R5") to non-CCR5-using ("non-R5") before and
      after viral suppression in the initially therapy-naive HOMER cohort from British
      Columbia, Canada. METHODS: We compared pre-therapy and post-suppression viral
      genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral
      regimens between 1996-1999 (n = 462). Virologic suppression was defined as having
      two consecutive viral loads of <500 copies/mL, which was the sensitivity limit of
      most viral load assays at the time. Viral tropism was inferred by V3-loop
      population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false
      positive rate (FPR). RESULTS: When virologic suppression was defined as two
      consecutive viral loads <500 copies/mL, 34 (9%) of the 397 patients with pre
      therapy R5-virus switched to non-R5 at viral load rebound after a median of 19
      months (IQR 8-41 months) of undetectable viremia. Duration of viral load
      suppression was not a predictor of switch, but lower CD4 count during suppression
      (median 400 versus 250 cells/mL) and an increased prevalence of pre-therapy non
      R5 HIV by "deep" sequencing (median 0.2% versus 3.2%) were independently
      associated with switch (p = 0.03 and p<0.0001, respectively). CONCLUSION: R5-to
      non-R5 tropism switches in plasma virus after undetectable viremia were
      relatively rare events especially among patients with higher CD4 counts during
      virologic suppression. Our study supports the use of pre-suppression tropism
      results if maraviroc is being considered during virologic suppression in this
      subgroup of patients.

PMID- 24905413
TI  - Sulfoximine-directed ruthenium-catalyzed ortho-C-H alkenylation of
      (hetero)arenes: synthesis of EP3 receptor antagonist analogue.
AB  - The reusable sulfoximine directing-group-assisted Ru(II)-catalyzed chemo- and
      regioselective ortho-C-H alkenylation of arenes and heteroarenes with acrylates
      and alpha,beta-unsaturated ketones/vinyl sulfone is shown. The N-aroyl
      sulfoximine undergoes annulation with diphenylacetylene, delivering
      isoquinolinones and methyl phenyl sulfoxide. The present protocol is successfully
      employed for the synthesis of the EP3 receptor antagonist analogue. 

PMID- 24905412
TI  - The use of guideline images to improve histological estimation of hepatic
      steatosis.
AB  - BACKGROUND & AIMS: Guideline images of specific fat proportionate area (FPA)
      percentages have recently been published to aid the histological assessment of
      liver steatosis as subjective estimates of FPA are usually overestimated. To
      assess, (i) the effect of guideline images on accuracy and concordance of
      estimated FPA (eFPA), (ii) experience of steatosis grading systems on eFPA, (iii)
      the effect of magnification on assessment of FPA (iv) and produce a range of
      guideline images at x4 objective magnification (OM). METHODS: Two circulations of
      sample images (C1 and C2) were circulated to UK liver external quality assessment
      histopathology scheme members who were asked to independently evaluate steatosis.
      Each circulation consisted of 15 images taken at both x20 and x4OM representing
      the full range of steatosis. C1 was distributed first, then C2 with guideline
      images of FPA 6 weeks later. RESULTS: Participants overestimated FPA in C1. In
      C2, there was significant improvement in accuracy (P < 0.001) of eFPA for sample
      images with mFPA >5%. Concordance of x4OM eFPA was substantial in both
      circulations (C1 K = 0.878, C2 K = 0.724). CONCLUSION: The tendency to
      overestimate eFPA has been corroborated and can be largely corrected with the use
      of guideline images (without needing digital image analysis). There is a need to
      redefine steatosis grades that are clinically significant and validated using an
      accurate quantification of steatosis.

PMID- 24905415
TI  - Recurrent pregnancy loss: a risk factor for long-term maternal atherosclerotic
      morbidity?
AB  - OBJECTIVE: We sought to investigate whether patients with a history of recurrent
      pregnancy loss (RPL) have an increased risk for future maternal atherosclerotic
      morbidity. STUDY DESIGN: A population-based study compared the incidence of long
      term atherosclerotic morbidity (renal and cardiovascular) in a cohort of women
      with and without a diagnosis of RPL. Patients had a mean follow-up duration of
      more than a decade. Women with known atherosclerotic disease were excluded from
      the study. Cardiovascular morbidity was divided into 4 categories according to
      severity and type including simple and complex cardiovascular events and invasive
      and noninvasive cardiac procedures. Kaplan-Meier survival curves were used to
      estimate cumulative incidence of cardiovascular and renal hospitalizations. Cox
      proportional hazards models were used to estimate the adjusted hazard ratios for
      cardiovascular and renal morbidity. RESULTS: During the study period 99,285
      patients were included; of these 6.7% (n = 6690) had a history of RPL. Patients
      with RPL had higher rates of renal and cardiovascular morbidity including cardiac
      invasive and noninvasive diagnostic procedures, simple as well as complex
      cardiovascular events, and hospitalizations due to cardiovascular causes. Using
      Kaplan-Meier survival curves, patients with a previous diagnosis of RPL had a
      significantly higher cumulative incidence of cardiovascular but not renal
      hospitalizations. Using a Cox proportional hazards model, adjusted for
      confounders such as preeclampsia, diabetes mellitus, obesity, and smoking, a
      history of RPL remained independently associated with cardiovascular
      hospitalizations (adjusted hazard ratio, 1.6; 95% confidence interval, 1.4-1.8; P
      = .001). CONCLUSION: RPL is an independent risk factor for long-term maternal
      cardiovascular complications.

PMID- 24905414
TI  - Modulating hydrogel crosslink density and degradation to control bone
      morphogenetic protein delivery and in vivo bone formation.
AB  - Bone morphogenetic proteins (BMPs) show promise in therapies for improving bone
      formation after injury; however, the high supraphysiological concentrations
      required for desired osteoinductive effects, off-target concerns, costs, and
      patient variability have limited the use of BMP-based therapeutics. To better
      understand the role of biomaterial design in BMP delivery, a matrix
      metalloprotease (MMP)-sensitive hyaluronic acid (HA)-based hydrogel was used for
      BMP-2 delivery to evaluate the influence of hydrogel degradation rate on bone
      repair in vivo. Specifically, maleimide-modified HA (MaHA) macromers were
      crosslinked with difunctional MMP-sensitive peptides to permit protease-mediated
      hydrogel degradation and growth factor release. The compressive, rheological, and
      degradation properties of MaHA hydrogels were characterized as a function of
      crosslink density, which was varied through either MaHA concentration (1-5wt.%)
      or maleimide functionalization (10-40%f). Generally, the compressive moduli
      increased, the time to gelation decreased, and the degradation rate decreased
      with increasing crosslink density. Furthermore, BMP-2 release increased with
      either a decrease in the initial crosslink density or an increase in collagenase
      concentration (non-specific MMP degradation). Lastly, two hydrogel formulations
      with distinct BMP-2 release profiles were evaluated in a critical-sized calvarial
      defect model in rats. After six weeks, minimal evidence of bone repair was
      observed within defects left empty or filled with hydrogels alone. For hydrogels
      that contained BMP-2, similar volumes of new bone tissue were formed; however,
      the faster degrading hydrogel exhibited improved cellular invasion, bone volume
      to total volume ratio, and overall defect filling. These results illustrate the
      importance of coordinating hydrogel degradation with the rate of new tissue
      formation. 

PMID- 24905416
TI  - Effect of lactation on maternal postpartum cardiac function and adiposity: a
      murine model.
AB  - OBJECTIVE: Lactation is associated with reduction in maternal metabolic disease
      and hypertension later in life; however, findings in humans may be confounded by
      socioeconomic factors. We sought to determine the independent contribution of
      lactation on cardiovascular parameters and adiposity in a murine model. STUDY
      DESIGN: Following delivery, CD-1 female mice were randomly divided into 2 groups:
      lactated (L; nursed pups for 3 weeks, n = 10), and nonlactated (NL; pups were
      removed after birth, n = 12). Blood pressure (BP) was assessed prepregnancy and
      at 1 and 2 months' postpartum. Visceral and subcutaneous adipose tissue
      determined by computed tomography and left ventricular ejection fraction, cardiac
      output, and the E/A ratio determined by microultrasound were evaluated at 1 and 2
      months' postpartum. The results were analyzed using a Student t test
      (significance at P < .05). RESULTS: We observed a significantly different
      maternal BP at 2 months' postpartum with relatively greater BP in NL (systolic
      BP: NL, 122.2 +/- 7.2 vs L, 96.8 +/- 9.8 mm Hg; P = .04; diastolic BP: NL, 87.0
      +/- 6.8 vs L, 65.9 +/- 6.2 mm Hg; P = .04). Visceral adipose tissue was
      significantly increased in NL mice at 1 (22.0 +/- 4.1% vs 10.7 +/- 1.8%, P = .04)
      and 2 months' postpartum (22.9 +/- 3.5% vs 11.2 +/- 2.2%, P = .02), whereas
      subcutaneous adipose tissue did not differ between the groups. At 2 months'
      postpartum, ejection fraction (51.8 +/- 1.5% vs 60.5 +/- 3.8%; P = .04), cardiac
      output (14.2 +/- 1.0 vs 18.0 +/- 1.3 mL/min; P = .02) and mitral valve E/A ratio
      (1.38 +/- 0.06 vs 1.82 +/- 0.13; P = .04) were significantly lower in NL mice
      than L mice. CONCLUSION: Our data provide evidence that interruption of lactation
      adversely affects postpartum maternal cardiovascular function and adiposity.

PMID- 24905417
TI  - Outcomes in pregnancies complicated by methamphetamine use.
AB  - OBJECTIVE: Methamphetamine use is widespread. Our goal was to examine the effects
      of methamphetamine use on various maternal and neonatal outcomes. STUDY DESIGN:
      We conducted a retrospective cohort study looking at all pregnancies between 2005
      and 2008 in the state of California that were associated with a diagnosis of
      methamphetamine use. Outcomes examined included gestational hypertension,
      preeclampsia, preterm birth, small for gestational age, birthweight, abruption,
      intrauterine fetal death, neonatal death, infant death, jaundice, and gestational
      diabetes mellitus. Statistical analysis included chi-squared tests and
      multivariable logistic regression analyses. RESULTS: After adjustment for
      multiple confounding variables on multivariable regression analysis, results
      indicated that compared with control subjects, methamphetamine users had greater
      odds of gestational hypertension (odds ratio [OR], 1.8; 95% confidence interval
      [CI], 1.6-2.0), preeclampsia (OR, 2.7; 95% CI, 2.4-3.0), intrauterine fetal death
      (OR, 5.1; 95% CI, 3.7-7.2), and abruption (OR, 5.5; 95% CI, 4.9-6.3).
      Additionally, these patients had higher odds of preterm birth (OR, 2.9; 95% CI,
      2.7-3.1), neonatal death (OR, 3.1; 95% CI, 2.3-4.2), and infant death (OR, 2.5;
      95% CI, 1.7-3.7). CONCLUSION: Methamphetamine use in pregnancy was found to be
      associated with specific patterns of increased maternal and fetal morbidity and
      death. With these results in mind, further work can be done to improve the care
      of pregnancies that are complicated by methamphetamine use in hopes of reducing
      these complications.

PMID- 24905418
TI  - Long-chain base phosphates modulate pollen tube growth via channel-mediated
      influx of calcium.
AB  - Long-chain base phosphates (LCBPs) have been correlated with amounts of crucial
      biological processes ranging from cell proliferation to apoptosis in animals.
      However, their functions in plants remain largely unknown. Here, we report that
      LCBPs, sphingosine-1-phosphate (S1P) and phytosphingosine-1-phosphate (Phyto
      S1P), modulate pollen tube growth in a concentration-dependent bi-phasic manner.
      The pollen tube growth in the stylar transmitting tissue was promoted by SPHK1
      overexpression (SPHK1-OE) but dampened by SPHK1 knockdown (SPHK1-KD) compared
      with wild-type of Arabidopsis; however, there was no detectable effect on in
      vitro pollen tube growth caused by misexpression of SPHK1. Interestingly,
      exogenous S1P or Phyto-S1P applications could increase the pollen tube growth
      rate in SPHK1-OE, SPHK1-KD and wild-type of Arabidopsis. Calcium ion (Ca(2+) )
      imaging analysis showed that S1P triggered a remarkable increase in cytosolic
      Ca(2+) concentration in pollen. Extracellular S1P induced hyperpolarization
      activated Ca(2+) currents in the pollen plasma membrane, and the Ca(2+) current
      activation was mediated by heterotrimeric G proteins. Moreover, the S1P-induced
      increase of cytosolic free Ca(2+) inhibited the influx of potassium ions in
      pollen tubes. Our findings suggest that LCBPs functions in a signaling cascade
      that facilitates Ca(2+) influx and modulates pollen tube growth. 

PMID- 24905419
TI  - Organometallic nucleoside analogues with ferrocenyl linker groups: synthesis and
      cancer cell line studies.
AB  - Examples of organometallic compounds as nucleoside analogues are rare within the
      field of medicinal bioorganometallic chemistry. We report on the synthesis and
      properties of two chiral ferrocene derivatives containing a nucleobase and a
      hydroxyalkyl group. These so-called ferronucleosides show promising anticancer
      activity, with cytostatic studies on five different cancer cell lines indicating
      that both functional groups are required for optimal activity.

PMID- 24905420
TI  - Confocal XANES and the Attic black glaze: the three-stage firing process through
      modern reproduction.
AB  - The decorated black- and red-figured Athenian vases (sixth and fifth century BC)
      and the plain black-glazed ware represent a milestone in our material culture due
      to their aesthetic and technological value; the Attic black glaze is of
      particular interest since it is a highly resistant potash-alumino-silicate glass,
      colored by magnetite nanocrystals (<200 nm). This study presents a new
      methodological approach for correlating the iron oxidation state in the black
      glaze layer with the manufacturing process by means of conventional and confocal
      X-ray absorption near edge spectroscopy (XANES). The enhanced surface sensitivity
      of confocal XANES is combined with conventional XANES resulting in higher
      counting rates to reliably evaluate the iron oxidation state (Fe(3+)/SigmaFe) of
      the surface layer. A detailed description of the new evaluation procedure is
      presented. The three-stage firing process was retraced by correlating selected
      attic black-glazed (BG) specimens from different periods (Archaic, Classical,
      Hellenistic) with laboratory reproductions. The modern BG specimens serving as
      reference samples were produced by following the three-stage firing process
      (i.e., under oxidizing-reducing-oxidizing (ORO) conditions) at different top
      temperatures, using clay suspensions of different particle size produced with
      treatment of raw illitic clays from Attica. 

PMID- 24905422
TI  - Effects of emotional eating and short sleep duration on weight gain in female
      employees.
AB  - OBJECTIVE: To investigate whether there is an interaction between emotional
      eating and sleep duration on weight change and whether this effect is stronger in
      women. DESIGN: One-year follow-up study. SETTING: Banking environment.
      PARTICIPANTS: 553 women and 911 men. MEASUREMENTS AND RESULTS: Self-reported
      emotional eating and body mass index (BMI) at T1 were measured in 2008, and sleep
      duration and BMI at follow-up (T2) were measured in 2009. A significant emotional
      eating-sleep duration interaction on BMI change was found in women, but not in
      men. CONCLUSIONS: The finding that the highest weight gain was found in women who
      combined short sleep duration with high emotional eating-both of them are markers
      of (chronic) distress-suggests a possible role of poor psychological health and
      (chronic) stress in this relationship.

PMID- 24905421
TI  - Health promotion in small business: a systematic review of factors influencing
      adoption and effectiveness of worksite wellness programs.
AB  - OBJECTIVE: To assess the evidence regarding the adoption and efficacy of worksite
      health promotion programs (WHPPs) in small businesses. METHODS: Peer-reviewed
      research articles were identified from a database search. Included articles were
      published before July 2013, described a study that used an experimental or
      quasiexperimental design and either assessed adoption of WHPPs or conducted
      interventions in businesses with fewer than 500 employees. A review team scored
      the study's rigor using the WHO-adapted GRADEprofiler "quality of evidence"
      criteria. RESULTS: Of the 84 retrieved articles, 19 met study inclusion criteria.
      Of these, only two met criteria for high rigor. CONCLUSIONS: Fewer small
      businesses adopt WHPPs compared with large businesses. Two high-rigor studies
      found that employees were healthier postintervention. Higher quality research is
      needed to better understand why small businesses rarely adopt wellness programs
      and to demonstrate the value of such programs.

PMID- 24905425
TI  - Rothia aeria endocarditis in a patient with a bicuspid aortic valve: case report.
AB  - Rothia aeria is an uncommon pathogen mainly associated with endocarditis in case
      reports. In previous reports, endocarditis by R. aeria was complicated by central
      nervous system embolization. In the case we report herein, endocarditis by R.
      aeria was diagnosed after acute self-limited diarrhea. In addition to the common
      translocation of R. aeria from the oral cavity, we hypothesize the possibility of
      intestinal translocation. Matrix-assisted laser desorption ionization-time of
      flight mass spectrometry and genetic sequencing are important tools that can
      contribute to early and more accurate etiologic diagnosis of severe infections
      caused by Gram-positive rods. 

PMID- 24905426
TI  - Punctuated equilibrium based on a locally ambiguous niche.
AB  - Punctuated equilibrium, recently regarded as the power law distribution of
      lifespan, is estimated with respect to self-organized criticality. Previous
      explanations were based on a global property, such as the selection of species
      depending on their fitness, however a particular entity defined through such
      global property cannot be relevant to the notion of "self". Here, we introduce
      local ambiguity of a niche with respect to function and define a function network
      by using two types of maps. Due to the local complex structure of the function
      network, motif and lateral connections, some species are easily replaced by
      others, and other species have long lives. Punctuated equilibrium can, therefore,
      be explained by local ambiguous interaction, which suggests the notion of self
      and supports the idea of self-organized criticality. 

PMID- 24905427
TI  - Association of exercise therapy and reduction of pain sensitivity in patients
      with knee osteoarthritis: a randomized controlled trial.
AB  - OBJECTIVE: Exercise has beneficial effects on pain in knee osteoarthritis (OA),
      yet the underlying mechanisms are unclear. The purpose of this study was to
      investigate the effects of exercise on pressure-pain sensitivity in patients with
      knee OA. METHODS: In a randomized controlled trial, participants were assigned to
      12 weeks of supervised exercise therapy (ET; 36 sessions) or a no attention
      control group (CG). Pressure-pain sensitivity was assessed by cuff pressure
      algometry on the calf of the most symptomatic leg. The coprimary outcomes were
      pressure-pain thresholds (PPTs) and cumulated visual analog scale pain scores
      during constant pressure for 6 minutes at 125% of the PPT as a measure of
      temporal summation (TS) of pressure-pain. Secondary outcomes included self
      reported pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS)
      questionnaire. Analyses were based on the "per-protocol" population (participants
      following the protocol). RESULTS: Sixty participants were randomized (31 in ET
      group, 29 in CG), and the per-protocol population included 48 participants (25 in
      ET group, 23 in CG). At followup, mean group differences in the change from
      baseline were 3.1 kPa (95% confidence interval [95% CI] 0.2, 6.0; P = 0.038) for
      the PPT, 2,608 mm * seconds (95% CI 458, 4,758; P = 0.019) for TS, and 6.8 points
      (95% CI 1.2, 12.4; P = 0.018) for KOOS pain, all in favor of ET. CONCLUSION:
      Pressure-pain sensitivity, TS, and self-reported pain are reduced among patients
      completing a 12-week supervised exercise program compared to a no attention CG.
      These results demonstrate beneficial effects of exercise on basic pain mechanisms
      and further exploration may provide a basis for optimized treatment.

PMID- 24905428
TI  - Predictability influences whether outcomes are processed in terms of original or
      relative values.
AB  - Previous studies have provided insights into the representations of original and
      relative values and the influence of predictability on decision making. However,
      whether the predictability of outcomes can influence the processing manner of
      outcomes (i.e. whether the outcomes are processed in terms of original or
      relative values) is still unknown. To investigate this issue, we had participants
      perform a monetary decision task which resulted in two outcomes with the same
      relative values but different original values in either a predictable or
      unpredictable condition, while recording event-related potentials (ERP). ERP
      results showed that the outcome processing in the unpredictable condition
      elicited more positive deflections in the time window of 300-500ms (P300) than
      did those in the predictable condition. More importantly, the outcome with high
      original value elicited a greater P300 component than did that with low original
      value in the unpredictable condition even though these two outcomes had the same
      relative values, while in the predictable condition no significant difference was
      observed between ERPs elicited by the two outcomes even though their original
      values were different. These results suggest that the outcomes might be processed
      in terms of relative values in the predictable condition but original values in
      the unpredictable condition. 

PMID- 24905429
TI  - Trial-to-trial dynamics of selective long-term-memory retrieval with continuously
      changing retrieval targets.
AB  - How do we control the successive retrieval of behaviorally relevant information
      from long-term memory (LTM) without being distracted by other potential retrieval
      targets associated to the same retrieval cues? Here, we approach this question by
      investigating the nature of trial-by-trial dynamics of selective LTM retrieval,
      i.e., in how far retrieval in one trial has detrimental or facilitatory effects
      on selective retrieval in the following trial. Participants first learned
      associations between retrieval cues and targets, with one cue always being linked
      to three targets, forming small associative networks. In successive trials,
      participants had to access either the same or a different target belonging to
      either the same or a different cue. We found that retrieval times were faster for
      targets that had already been relevant in the previous trial, with this
      facilitatory effect being substantially weaker when the associative network
      changed in which the targets were embedded. Moreover, staying within the same
      network still had a facilitatory effect even if the target changed, which became
      evident in a relatively higher memory performance in comparison to a network
      change. Furthermore, event-related brain potentials (ERPs) showed topographically
      and temporally dissociable correlates of these effects, suggesting that they
      result from combined influences of distinct processes that aid memory retrieval
      when relevant and irrelevant targets change their status from trial to trial.
      Taken together, the present study provides insight into the different processing
      stages of memory retrieval when fast switches between retrieval targets are
      required. 

PMID- 24905430
TI  - A combined metabolomic and phylogenetic study reveals putatively prebiotic
      effects of high molecular weight arabino-oligosaccharides when assessed by in
      vitro fermentation in bacterial communities derived from humans.
AB  - Prebiotic oligosaccharides are defined by their selective stimulation of growth
      and/or activity of bacteria in the digestive system in ways claimed to be
      beneficial for health. However, apart from the short chain fatty acids, little is
      known about bacterial metabolites created by fermentation of prebiotics, and the
      significance of the size of the oligosaccharides remains largely unstudied. By in
      vitro fermentations in human fecal microbial communities (derived from six
      different individuals), we studied the effects of high-mass (HA, >1 kDa), low
      mass (LA, <1 kDa) and mixed (BA) sugar beet arabino-oligosaccharides (AOS) as
      carbohydrate sources. Fructo-oligosaccharides (FOS) were included as reference.
      The changes in bacterial communities and the metabolites produced in response to
      incubation with the different carbohydrates were analyzed by quantitative PCR
      (qPCR) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. All
      tested carbohydrate sources resulted in a significant increase of Bifidobacterium
      spp. between 1.79 fold (HA) and 1.64 fold (FOS) in the microbial populations
      after fermentation, and LC-MS analysis suggested that the bifidobacteria
      contributed to decomposition of the arabino-oligosaccharide structures, most
      pronounced in the HA fraction, resulting in release of the essential amino acid
      phenylalanine. Abundance of Lactobacillus spp. correlated with the presence of a
      compound, most likely a flavonoid, indicating that lactobacilli contribute to
      release of such health-promoting substances from plant structures. Additionally,
      the combination of qPCR and LC-MS revealed a number of other putative
      interactions between intestinal microbes and the oligosaccharides, which
      contributes to the understanding of the mechanisms behind prebiotic impact on
      human health. 

PMID- 24905431
TI  - Regulation of NucB2/Nesfatin-1 throughout rat pregnancy.
AB  - Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage
      from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region
      (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases.
      This neuropeptide was originally localized in different appetite controlling
      areas such as the hypothalamic paraventricular nucleus, arcuate nucleus,
      supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius.
      The objective of this study was to determine the expression and the changes that
      occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation.
      This study utilized molecular and immunological approaches to investigate the
      expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat
      fed under ad libitum and food restricted conditions (30% nutrient restriction).
      NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin
      1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19
      and 21, showing a significant (p<0.01) decrease in serum levels after day 12
      until the end of gestation in rats fed ad libitum. These results were correlated
      with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed
      in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21.
      It was also observed that food restriction decreases Nesfatin-1 serum levels and
      NucB2 placental expression at day 16 of gestation when compared to pregnant rats
      fed ad libitum. This study illustrates for the first time through molecular and
      immunological approaches the NucB2 expression and regulation on rat placenta and
      that this peptide is regulated throughout pregnancy. Consistent with previous
      reports, our results provide additional evidence supporting the role of NucB2
      protein as an anorexigenic peptide that may contribute to the regulation of
      feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important
      metabolic role during pregnancy and fetal development and its energy balance
      mediating role should be studied in various physiological and pathological
      conditions throughout gestation. 

PMID- 24905432
TI  - Increased objectively assessed vigorous-intensity exercise is associated with
      reduced stress, increased mental health and good objective and subjective sleep
      in young adults.
AB  - The role of physical activity as a factor that protects against stress-related
      mental disorders is well documented. Nevertheless, there is still a dearth of
      research using objective measures of physical activity. The present study
      examines whether objectively assessed vigorous physical activity (VPA) is
      associated with mental health benefits beyond moderate physical activity (MPA).
      Particularly, this study examines whether young adults who accomplish the
      American College of Sports Medicine's (ACSM) vigorous-intensity exercise
      recommendations differ from peers below these standards with regard to their
      level of perceived stress, depressive symptoms, perceived pain, and subjective
      and objective sleep. A total of 42 undergraduate students (22 women, 20 men;
      M=21.24years, SD=2.20) volunteered to take part in the study. Stress, pain,
      depressive symptoms, and subjective sleep were assessed via questionnaire,
      objective sleep via sleep-EEG assessment, and VPA via actigraphy. Meeting VPA
      recommendations had mental health benefits beyond MPA. VPA was associated with
      less stress, pain, subjective sleep complaints and depressive symptoms. Moreover,
      vigorous exercisers had more favorable objective sleep pattern. Especially, they
      had increased total sleep time, more stage 4 and REM sleep, more slow wave sleep
      and a lower percentage of light sleep. Vigorous exercisers also reported fewer
      mental health problems if exposed to high stress. This study provides evidence
      that meeting the VPA standards of the ACSM is associated with improved mental
      health and more successful coping among young people, even compared to those who
      are meeting or exceeding the requirements for MPA. 

PMID- 24905434
TI  - Educating parents on gastrostomy devices: necessary components to achieve
      success.
AB  - Often parents leave the hospital without the education needed to care for their
      child's gastrostomy device. Lack of nurse knowledge and the use of various types
      of devices contribute to their confusion and inability to adequately educate
      parents. An enhanced methodology and process to standardize gastrostomy education
      were designed and implemented. Data results confirmed an improvement in the
      knowledge and competency of both staff nurses and parents. Empowering staff
      nurses with knowledge and the necessary resources and tools to confidently
      educate parents, along with a standardized process, has improved overall
      outcomes. 

PMID- 24905435
TI  - In situ intercalation dynamics in inorganic-organic layered perovskite thin
      films.
AB  - The properties of layered inorganic semiconductors can be manipulated by the
      insertion of foreign molecular species via a process known as intercalation. In
      the present study, we investigate the phenomenon of organic moiety (R-NH3I)
      intercalation in layered metal-halide (PbI2)-based inorganic semiconductors,
      leading to the formation of inorganic-organic (IO) perovskites [(R-NH3)2PbI4].
      During this intercalation strong resonant exciton optical transitions are
      created, enabling study of the dynamics of this process. Simultaneous in situ
      photoluminescence (PL) and transmission measurements are used to track the
      structural and exciton evolution. On the basis of the experimental observations,
      a model is proposed which explains the process of IO perovskite formation during
      intercalation of the organic moiety through the inorganic semiconductor layers.
      The interplay between precursor film thickness and organic solution
      concentration/solvent highlights the role of van der Waals interactions between
      the layers, as well as the need for maintaining stoichiometry during
      intercalation. Nucleation and growth occurring during intercalation matches a
      Johnson-Mehl-Avrami-Kolmogorov model, with results fitting both ideal and
      nonideal cases. 

PMID- 24905433
TI  - The complex roles of NADPH oxidases in fungal infection.
AB  - NADPH oxidases play key roles in immunity and inflammation that go beyond the
      production of microbicidal reactive oxygen species (ROS). The past decade has
      brought a new appreciation for the diversity of roles played by ROS in signalling
      associated with inflammation and immunity. NADPH oxidase activity affects disease
      outcome during infections by human pathogenic fungi, an important group of
      emerging and opportunistic pathogens that includes Candida, Aspergillus and
      Cryptococcus species. Here we review how alternative roles of NADPH oxidase
      activity impact fungal infection and how ROS signalling affects fungal
      physiology. Particular attention is paid to roles for NADPH oxidase in immune
      migration, immunoregulation in pulmonary infection, neutrophil extracellular trap
      formation, autophagy and inflammasome activity. These recent advances highlight
      the power and versatility of spatiotemporally controlled redox regulation in the
      context of infection, and point to a need to understand the molecular
      consequences of NADPH oxidase activity in the cell.

PMID- 24905436
TI  - Overcompensation and phase effects in a cyclic common vole population: between
      first and second-order cycles.
AB  - Population cycles in voles are often thought to be generated by one-year delayed
      density dependence on the annual population growth rate. In common voles,
      however, it has been suggested by Turchin (2003) that some populations exhibit
      first-order cycles, resulting from strong overcompensation (i.e. carrying
      capacity overshoots in peak years, with only an effect of the current year
      abundance on annual growth rates). We focus on a common vole (Microtus arvalis)
      population from western France that exhibits 3-year cycles. Several
      overcompensating nonlinear models for populations dynamics are fitted to the
      data, notably those of Hassell, and Maynard-Smith and Slatkin. Overcompensating
      direct density dependence (DD) provides a satisfactory description of winter
      crashes, and one-year delayed density dependence is not responsible for the
      crashes, thus these are not classical second-order cycles. A phase-driven
      modulation of direct density dependence maintains a low-phase, explaining why the
      cycles last three years instead of two. Our analyses suggest that some of this
      phase dependence can be expressed as one-year delayed DD, but phase dependence
      provides a better description. Hence, modelling suggests that cycles in this
      population are first-order cycles with a low phase after peaks, rather than fully
      second-order cycles. However, based on the popular log-linear second-order
      autoregressive model, we would conclude only that negative delayed density
      dependence exists. The additive structure of this model cannot show when delayed
      DD occurs (here, during lows rather than peaks). Our analyses thus call into
      question the automated use of second-order log-linear models, and suggests that
      more attention should be given to non-(log)linear models when studying cyclic
      populations. From a biological viewpoint, the fast crashes through
      overcompensation that we found suggest they might be caused by parasites or food
      rather than predators, though predators might have a role in maintaining the low
      phase and spatial synchrony. 

PMID- 24905438
TI  - Enhanced visual responses in the superior colliculus in an animal model of
      attention-deficit hyperactivity disorder and their suppression by D-amphetamine.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental
      disorder characterized by overactivity, impulsiveness and attentional problems,
      including an increase in distractibility. A structure that is intimately linked
      with distractibility is the superior colliculus (SC), a midbrain sensory
      structure which plays a particular role in the production of eye and head
      movements. Although others have proposed the involvement of such diverse elements
      as the frontal cortex and forebrain noradrenaline in ADHD, given the role of the
      colliculus in distractibility and the increased distractibility in ADHD, we have
      proposed that distractibility in ADHD arises due to collicular sensory hyper
      responsiveness. To further investigate this possibility, we recorded the
      extracellular activity (multi-unit (MUA) and local field potential (LFP)) in the
      superficial visual layers of the SC in an animal model of ADHD, the New Zealand
      genetically hypertensive (GH) rat, in response to wholefield light flashes. The
      MUA and LFP peak amplitude and summed activity within a one-second time window
      post-stimulus were both significantly greater in GH rats than in Wistar controls,
      across the full range of stimulus intensities. Given that baseline firing rate
      did not differ between the strains, this suggests that the signal-to-noise ratio
      is elevated in GH animals. D-Amphetamine reduced the peak amplitude and summed
      activity of the multi-unit response in Wistar animals. It also reduced the peak
      amplitude and summed activity of the multi-unit response in GH animals, at higher
      doses bringing it down to levels that were equivalent to those of Wistar animals
      at baseline. The present results provide convergent evidence that a collicular
      dysfunction (sensory hyper-responsiveness) is present in ADHD, and that it may
      underlie the enhanced distractibility. In addition, D-amphetamine - a widely used
      treatment in ADHD - may have one of its loci of therapeutic action at the level
      of the colliculus.

PMID- 24905439
TI  - Corticosterone affects the differentiation of a neuronal cerebral cortex-derived
      cell line through modulation of the nicotinic acetylcholine receptor.
AB  - Chronic exposure to stress hormones has an impact on brain structures relevant to
      cognition. Nicotinic acetylcholine receptors (AChRs) are involved in numerous
      cognitive processes including learning and memory formation. In order to better
      understand the molecular mechanisms of chronic stress-triggered mental disease,
      the effect of corticosterone (CORT) on the biology of AChRs was studied in the
      neuronal cell line CNh. We found that chronic treatment with CORT reduced the
      expression levels of the alpha7-type neuronal AChR and, to a lesser extent, of
      alpha4-AChR. CORT also delayed the acquisition of the mature cell phenotype in
      CNh cells. Chronic nicotine treatment affected the differentiation of CNh cells
      and exerted a synergistic effect with CORT, suggesting that AChR could
      participate in signaling pathways that control the cell cycle. Overexpression of
      alpha7-AChR-GFP abolished the CORT effects on the cell cycle and the specific
      alpha7-AChR inhibitor, methyllycaconitine, mimicked the proliferative action
      exerted by CORT. Whole-cell voltage-clamp recordings showed a significant
      decrease in nicotine-evoked currents in CORT-treated cells. Taken together, these
      observations indicate that AChRs, and the alpha7-AChR in particular, could act as
      modulators of the differentiation of CNh cells and that CORT could impair the
      acquisition of a mature phenotype by affecting the function of this AChR subtype.

PMID- 24905437
TI  - Astrocytes, but not microglia, are activated in oxaliplatin and bortezomib
      induced peripheral neuropathy in the rat.
AB  - Spinal microglia are widely recognized as activated by and contributing to the
      generation and maintenance of inflammatory and nerve injury related chronic pain;
      whereas the role of spinal astrocytes has received much less attention, despite
      being the first glial cells identified as activated following peripheral nerve
      injury. Recently it was suggested that microglia do not appear to play a
      significant role in chemotherapy-induced peripheral neuropathy (CIPN), but in
      contrast astrocytes appear to have a key role. In spite of the generalizability
      of astrocyte recruitment across chemotherapy drugs, its correlation to the onset
      of the behavioral CIPN phenotype has not been determined. The astroglial and
      microglial markers glial fibrillary acidic protein (GFAP) and OX-42 were imaged
      here to examine glial reactivity in multiple models of CIPN over time and to
      contrast this response to that produced in the spinal nerve ligation (SNL) model.
      Microglia were strongly activated following SNL, but not activated at any of the
      time points observed following chemotherapy treatments. Astrocytes were activated
      following both oxaliplatin and bortezomib treatment in a manner that paralleled
      chemotherapy-evoked behavioral changes. Both the behavioral phenotype and
      activation of astrocytes were prevented by co-administration of minocycline
      hydrochloride in both CIPN models, suggesting a common mechanism. 

PMID- 24905441
TI  - Triphenylphosphine oxide-catalyzed stereoselective poly- and dibromination of
      unsaturated compounds.
AB  - A novel PPh3O catalyzed bromophosphonium salt-mediated dibromination of
      alpha,beta-unsaturated esters and beta,gamma-unsaturated alpha-ketoesters has
      been developed. The products were obtained with good to excellent yields and
      excellent diastereoselectivities. This dibromination reaction is a good
      complement to the field of dibromination. 

PMID- 24905440
TI  - Prostate progenitor cells proliferate in response to castration.
AB  - Androgen-deprivation is a mainstay of therapy for advanced prostate cancer but
      tumor regression is usually incomplete and temporary because of androgen
      independent cells in the tumor. It has been speculated that these tumor cells
      resemble the stem/progenitor cells of the normal prostate. The purpose of this
      study was to examine the response of slow-cycling progenitor cells in the adult
      mouse prostate to castration. Proliferating cells in the E16 urogenital sinus
      were pulse labeled by BrdU administration or by doxycycline-controlled labeling
      of the histone-H2B GFP mouse. A small population of labeled epithelial cells in
      the adult prostate localized at the junction of the prostatic ducts and urethra.
      Fluorescence-activated cell sorting (FACS) showed that GFP label-retaining cells
      were enriched for cells co-expressing stem cell markers Sca-1, CD133, CD44 and
      CD117 (4- marker cells; 60-fold enrichment). FACS showed, additionally, that 4
      marker cells were androgen receptor positive. Castration induced proliferation
      and dispersal of E16 labeled cells into more distal ductal segments. When naive
      adult mice were administered BrdU daily for 2 weeks after castration, 16% of 4
      marker cells exhibited BrdU label in contrast to only 6% of all epithelial cells
      (P<0.01). In sham-castrated controls less than 4% of 4-marker cells were BrdU
      labeled (P<0.01). The unexpected and admittedly counter-intuitive finding that
      castration induced progenitor cell proliferation suggests that androgen
      deprivation therapy in men with advanced prostate cancer could not only exert
      pleiotrophic effects on tumor sub-populations but may induce inadvertent
      expansion of tumor stem cells.

PMID- 24905442
TI  - Increased expression of TIGIT on CD4+ T cells ameliorates immune-mediated bone
      marrow failure of aplastic anemia.
AB  - Aplastic anemia (AA) is an autoimmune disease in which T cell activation is
      suspected to play an important role. T cell immunoglobulin and ITIM
      (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) is an inhibitory
      receptor, which exhibits inhibitory functions on the immune response. However,
      its role in AA has not been clearly determined. In the current study, we showed
      that the frequency of TIGIT-positive CD4(+) T cells was reduced in the vast
      majority of AA patients (85%, 17/20). In TIGIT-silenced human CD4(+) T cells,
      stimulation of agonistic anti-TIGIT monoclonal antibody significantly facilitated
      cell proliferation, increased production of IL-2 and IFN-gamma, and inhibited
      production of IL-10. However, in TIGIT-overexpressed human CD4(+) T cells, cell
      proliferation and the production of IL-2, IFN-gamma, and TNF-alpha were
      significantly hindered; in contrast, the secretion of IL-10 was improved. RT-PCR
      and Western blotting showed that T-bet expression in human CD4(+) T cells was
      significantly decreased by TIGIT overexpression, but only slightly altered by
      TIGIT knockdown. In mouse models, lentivirus-mediated TIGIT-overexpressed CD4(+)
      T cell transfer significantly rescued the decreased red blood cell count,
      attenuated the increase in serum INF-gamma and TNF-alpha levels, and lengthened
      the median survival time. The mRNA levels of CD34, stem cell factor (SCF), and
      granulocyte/macrophage-colony-stimulating factor (GM-CSF) in bone marrow
      mononuclear cells were also up-regulated. In conclusion, increased expression of
      TIGIT could inhibit the function of CD4(+) T cells in vitro and ameliorate immune
      mediated bone marrow failure of AA in vivo providing a new potential strategy for
      the treatment of AA.

PMID- 24905443
TI  - Monolithically integrated mid-infrared lab-on-a-chip using plasmonics and quantum
      cascade structures.
AB  - The increasing demand of rapid sensing and diagnosis in remote areas requires the
      development of compact and cost-effective mid-infrared sensing devices. So far,
      all miniaturization concepts have been demonstrated with discrete optical
      components. Here we present a monolithically integrated sensor based on mid
      infrared absorption spectroscopy. A bi-functional quantum cascade laser/detector
      is used, where, by changing the applied bias, the device switches between laser
      and detector operation. The interaction with chemicals in a liquid is resolved
      via a dielectric-loaded surface plasmon polariton waveguide. The thin dielectric
      layer enhances the confinement and enables efficient end-fire coupling from and
      to the laser and detector. The unamplified detector signal shows a slope of 1.8-7
      MUV per p.p.m., which demonstrates the capability to reach p.p.m. accuracy over a
      wide range of concentrations (0-60%). Without any hybrid integration or
      subwavelength patterning, our approach allows a straightforward and cost-saving
      fabrication.

PMID- 24905444
TI  - Simultaneous kissing stent in a patient with severe bifurcation pulmonary vein
      stenosis.
AB  - Pulmonary vein stenosis (PVS) is a late and rare complication of pulmonary vein
      isolation for the treatment of atrial fibrillation. The ideal approach to the
      management of PVS has not yet been established, however, corrective procedures
      may include both surgical and percutaneous techniques. We describe the case of a
      complex bifurcation lesion involving the left superior pulmonary vein. The
      condition required percutaneous intervention using a modified kissing stent
      technique with bare metal stents that resulted in an excellent post-operative
      course, sustained symptomatic relief, and uncomplicated 1-year follow-up. (c)
      2014 Wiley Periodicals, Inc. 

PMID- 24905445
TI  - Use of triple ultra-high-pressure balloons for obstructed right ventricular
      outflow conduits in adults can be safe and effective.
AB  - To date, no transcatheter valve has been approved for placement in the pulmonary
      position in Japan. Consequently, percutaneous balloon dilatation may be advised
      for stenotic right ventricular outflow lesions; however, technical difficulties
      persist, particularly in adults. We describe the acute haemodynamic changes and
      outcome of balloon dilatation of right ventricular outflow obstruction using
      triple ultra-high pressure balloons. This is the first report of such a technical
      development, which seems to be safe and effective. A total of three adult
      patients, aged 25, 29, and 37 years, with severe conduit obstruction were
      referred for balloon dilatation. A triple ultra-high-pressure balloon technique
      was used in the three patients after unsuccessful double-balloon dilatation, or
      for highly calcified lesions, which were expected to require ultra-high pressure
      for effective relief. Following balloon dilatation, the pressure gradient
      decreased from 24, 30, 65 to 3, 25, 30 mmHg, respectively. There were no
      procedural complications except slightly increased pulmonary regurgitation.
      Balloon dilatation using a triple ultra-high pressure balloon technique can be a
      safe and effective palliative procedure for conduit obstruction in adult
      patients. 

PMID- 24905446
TI  - A domino approach to the enantioselective total syntheses of blennolide C and
      gonytolide C.
AB  - The first enantioselective total syntheses of the tetrahydroxanthenone (-)
      blennolide C (ent-4) and related gamma-lactonyl chromanone (-)-gonytolide C (ent
      3) are reported. Key to the syntheses is an enantioselective domino
      Wacker/carbonylation/methoxylation reaction to set up the stereocentre at C-4a.
      Various chiral BOXAX ligands were investigated, including novel (S,S)-iBu-BOXAX,
      and allowed access to chromane 8 in an excellent enantioselectivity of 99 %. The
      second stereocentre at C-4 was established employing a diastereoselective
      Sharpless dihydroxylation. An extensive survey of (DHQ)- and (DHQD)-based ligands
      enabled the preparation of both the anti-isomer 14 a and the syn-isomer 14 b in
      very good to reasonable selectivities of 13.7:1 and 1:3.7, respectively. While 14
      a was further converted to ent-3 and ent-4, 14 b was elaborated to syn-acid 25
      and 2'-epi-gonytolide C 28. 

PMID- 24905447
TI  - Low serum potassium concentration is a predictor of chronic kidney disease.
AB  - AIMS: The aim of this study was to examine whether low serum potassium
      concentration could be a predictor of chronic kidney disease (CKD) in a community
      based cohort. MATERIALS AND METHODS: We enrolled 1001 subjects, median period of
      5.7 years, and evaluated the risk factors for CKD, defined as estimated
      glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), and assessed whether low
      serum potassium concentration could predict CKD. RESULTS: Compared with the
      subjects without development of CKD, age, body mass index, fasting plasma
      glucose, uric acid (UA), creatinine and serum sodium concentration were higher,
      and serum potassium concentration was lower in subjects with development of CKD.
      Univariate Cox regression analyses demonstrated that age, body mass index,
      fasting plasma glucose, UA, creatinine, serum sodium concentration and serum
      potassium concentration were associated with progression of CKD. Multiple Cox
      regression analysis revealed that age, gender, creatinine and serum potassium
      concentration were independent predictors of CKD after adjustment for covariates.
      When serum potassium concentration was below 4.0 mmol/l at baseline, hazard ratio
      (95% confidence interval) of developing CKD was 2.65 (2.04-3.44; p < 0.0001).
      CONCLUSIONS: Serum potassium concentration could be a clinically relevant risk
      factor for the progression of CKD, defined as eGFR < 60 ml/min/1.73 m(2) , in
      healthy subjects.

PMID- 24905448
TI  - The effect of maternal low-protein diet on the heart of adult offspring: role of
      mitochondria and oxidative stress.
AB  - Protein restriction during perinatal and early postnatal development is
      associated with a greater incidence of disease in the adult, such arterial
      hypertension. The aim in the present study was to investigate the effect of
      maternal low-protein diet on mitochondrial oxidative phosphorylation capacity,
      mitochondrial reactive oxygen species (ROS) formation, antioxidant levels
      (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the
      adult offspring. Pregnant Wistar rats received either 17% casein (normal protein,
      NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After
      weaning male progeny of these NP or LP fed rats, females were maintained on
      commercial chow (Labina-Purina). At 100 days post-birth, the male rats were
      sacrificed and heart tissue was harvested and stored at -80  degrees C. Our
      results show that restricting protein consumption in pregnant females induced
      decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP
      stimulated oxygen consumption and 49.5% reduction in respiratory control ratio)
      in their progeny when compared with NP group. In addition, maternal low-protein
      diet induced a significant decrease in enzymatic antioxidant capacity (37.8%
      decrease in superoxide dismutase activity; 42% decrease in catalase activity;
      44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in
      glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and
      glutathione level (34.8% decrease) when compared with control. From these
      findings, we hypothesize that an increased production of ROS and decrease in
      antioxidant activity levels induced by protein restriction during development
      could potentiate the progression of metabolic and cardiac diseases in adulthood. 

PMID- 24905449
TI  - Prognostic factors for myositis-associated interstitial lung disease.
AB  - BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of
      polymyositis (PM), dermatomyositis (DM), and clinically amyopathic
      dermatomyositis (CADM); however, little is known about the factors influencing
      the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the
      present study is to assess prognostic factors for PM/DM/CADM-ILD. METHODS: The
      clinical features and survival of 114 consecutive patients diagnosed with
      PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed
      retrospectively. RESULTS: The study group included 30 PM-associated ILD, 41 DM
      associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of
      ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55
      patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever.
      High-resolution computed tomography frequently revealed ground-glass opacities,
      traction bronchiectasis, and consolidation. Most of the patients were treated
      with corticosteroids or corticosteroids in combination with immunosuppressive
      agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital
      capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and
      a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in
      univariate Cox proportional hazards models. Multivariate Cox proportional hazards
      analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM)
      as significant predictors of overall mortality. Patients with acute/subacute ILD
      had a much lower survival rate than those with the chronic form (p<0.001).
      Patients with CADM-ILD had a lower survival rate than those with PM-ILD (p =
      0.034). CONCLUSIONS: Acute/subacute form, older age, lower level of FVC and
      diagnosis of CADM predict poor outcome in PM/DM/CADM-ILD.

PMID- 24905450
TI  - Current Phase II investigational proteasome inhibitors for the treatment of
      multiple myeloma.
AB  - INTRODUCTION: The introduction and exploration of novel agents has significantly
      improved patient outcome in the treatment of multiple myeloma (MM). One such
      compound, bortezomib, was the first proteasome inhibitor (PI) to be approved as a
      MM therapeutic. The efficacy and safety data provided by bortezomib usage has
      provided the basis for the development of a second generation of PIs. AREAS
      COVERED: This review focuses on PIs that are currently under evaluation in Phase
      II clinical trials for the treatment of MM. Furthermore, the article summarizes
      the currently understood mechanisms of action and the available clinical data for
      its use in MM. EXPERT OPINION: Second generation PIs have demonstrated promising
      activity in patients with advanced-stage myeloma, including those refractory to
      bortezomib. It should be noted, however, that their efficacy in upfront settings
      is currently under investigation. Future PI development should include schedule
      optimization and the investigation of PIs potential synergistic activity with
      other anti-myeloma agents.

PMID- 24905451
TI  - The physical activity energy cost of the latest active video games in young
      adults.
AB  - BACKGROUND: Although promoted for weight loss, especially in young adults, it has
      yet to be determined if the physical activity energy expenditure (PAEE) and
      intensity of the newest active video games (AVGs) qualifies as moderate-to
      vigorous physical activity (MVPA; > 3.0 METs). This study compared the PAEE and
      intensity of AVGs to traditional seated video games (SVGs). METHODS: Fifty-three
      young adults (18-35 y; 27 females) volunteered to play 6 video games (4 AVGs, 2
      SVGs). Anthropometrics and resting metabolism were measured before testing. While
      playing the games (6-10 min) in random order against a playmate, the participants
      wore a portable metabolic analyzer for measuring PAEE (kcal/min) and intensity
      (METs). A repeated-measures ANOVA compared the PAEE and intensity across games
      with sex, BMI, and PA status as main effects. RESULTS: The intensity of AVGs (6.1
      +/- 0.2 METs) was significantly greater than SVGs (1.8 +/- 0.1 METs). AVGs
      elicited greater PAEE than SVGs in all participants (5.3 +/- 0.2 vs 0.8 +/- 0.0
      kcal/min); PAEE during the AVGs was greater in males and overweight participants
      compared with females and healthy weight participants (p's < .05). CONCLUSIONS:
      The newest AVGs do qualify as MVPA and can contribute to the recommended dose of
      MVPA for weight management in young adults.

PMID- 24905452
TI  - Coupling of elasticity to capillarity in soft aerated materials.
AB  - We study the elastic properties of soft solids containing air bubbles. Contrary
      to standard porous materials, the softness of the matrix allows for a coupling of
      the matrix elasticity to surface tension forces acting on the bubble surface.
      Thanks to appropriate experiments on model systems, we demonstrate how the
      elastic response of the soft porous solid is governed by two dimensionless
      parameters: the gas volume fraction and a capillary number comparing the
      elasticity of the matrix with the stiffness of the bubbles. Furthermore, we show
      that our experimental results are accurately predicted by computations of the
      shear modulus through a micro-mechanical approach. 

PMID- 24905453
TI  - Comparative analysis of glucuronidation of ethanol in treeshrews, rats and
      humans.
AB  - 1. The treeshrews consume food-derived alcohol (ethanol) at a dose that would
      intoxicate humans, highlighting a marked difference in detoxification of ethanol
      between the animal species and humans. 2. In this study, we reported that the
      treeshrews and rats exhibited considerably high glucuronidation capacity for
      ethanol. Ethanol glucuronidation was 7.1-fold (for the liver microsomes) or 29.2
      fold (for the intestine microsomes) more efficient in treeshrews than in humans.
      Similar to treeshrews, rats also showed a high efficiency in glucuronidating
      ethanol. 3. In the single-pass perfused intestinal model, significant amount of
      ethyl glucuronide (EtG) was excreted into the perfusate (for both treeshrews and
      rats) and bile (for rats). Biliary excretion of EtG was 8.8-13.4 times of
      intestinal excretion of EtG, suggesting that the liver played a determinant role
      in glucuronidation of ethanol. In vivo pharmacokinetics showed that EtG
      production was rapid in the animals with a Tmax value of <= 1.75 h. The excreted
      EtG into urine was 0.11-0.13% of dosed ethanol, a value increased by a 5.5- to
      6.6-fold compared to that in humans. 4. This was the first report that the
      glucuronidation activity toward ethanol was much higher in treeshrews and rats
      than that in humans, revealing a marked species difference in ethanol
      glucuronidation.

PMID- 24905454
TI  - Additional nitrogen fertilization at heading time of rice down-regulates
      cellulose synthesis in seed endosperm.
AB  - The balance between carbon and nitrogen is a key determinant of seed storage
      components, and thus, is of great importance to rice and other seed-based food
      crops. To clarify the influence of the rhizosphere carbon/nitrogen balance during
      the maturation stage of several seed components, transcriptome analysis was
      performed on the seeds from rice plants that were provided additional nitrogen
      fertilization at heading time. As a result, it was assessed that genes associated
      with molecular processes such as photosynthesis, trehalose metabolism, carbon
      fixation, amino acid metabolism, and cell wall metabolism were differentially
      expressed. Moreover, cellulose and sucrose synthases, which are involved in
      cellulose synthesis, were down-regulated. Therefore, we compared cellulose
      content of mature seeds that were treated with additional nitrogen fertilization
      with those from control plants using calcofluor staining. In these experiments,
      cellulose content in endosperm from plants receiving additional nitrogen
      fertilization was less than that in control endosperm. Other starch synthesis
      related genes such as starch synthase 1, starch phosphorylase 2, and branching
      enzyme 3 were also down-regulated, whereas some alpha-amylase and beta-amylase
      genes were up-regulated. On the other hand, mRNA expression of amino acid
      biosynthesis-related molecules was up-regulated. Moreover, additional nitrogen
      fertilization caused accumulation of storage proteins and up-regulated Cys-poor
      prolamin mRNA expression. These data suggest that additional nitrogen
      fertilization at heading time changes the expression of some storage substance
      related genes and reduces cellulose levels in endosperm. 

PMID- 24905455
TI  - KIAA1524/CIP2A promotes cancer growth by coordinating the activities of MTORC1
      and MYC.
AB  - KIAA1524/CIP2A/cancerous inhibitor of protein phosphatase 2A is a cancer
      promoting protein that stabilizes the MYC proto-oncogene protein by inhibiting
      its dephosphorylation. Our recent report demonstrates that KIAA1524/CIP2A
      supports cancer cell growth also at the level of the mechanistic target of
      rapamycin complex 1 (MTORC1), a key signaling module that drives cell growth by
      stimulating protein synthesis and inhibiting autophagy. KIAA1524/CIP2A suppresses
      MTORC1-associated protein phosphatase 2A (PP2A) activity in an allosteric manner
      thereby stabilizing the phosphorylation of MTORC1 substrates and keeping the cell
      in an anabolic mode. In the absence of growth stimulating signals or nutrients,
      reduced MTORC1 activity triggers SQSTM1/p62-dependent autophagic degradation of
      KIAA1524/CIP2A enhancing the PP2A-mediated dephosphorylation of MTORC1 substrates
      and MYC. Thus, KIAA1524/CIP2A emerges as an oncoprotein that can coordinate the
      growth-promoting activities of MTORC1 and MYC in response to environmental and
      intrinsic cues. 

PMID- 24905456
TI  - MicroRNA array normalization: an evaluation using a randomized dataset as the
      benchmark.
AB  - MicroRNA arrays possess a number of unique data features that challenge the
      assumption key to many normalization methods. We assessed the performance of
      existing normalization methods using two microRNA array datasets derived from the
      same set of tumor samples: one dataset was generated using a blocked
      randomization design when assigning arrays to samples and hence was free of
      confounding array effects; the second dataset was generated without blocking or
      randomization and exhibited array effects. The randomized dataset was assessed
      for differential expression between two tumor groups and treated as the
      benchmark. The non-randomized dataset was assessed for differential expression
      after normalization and compared against the benchmark. Normalization improved
      the true positive rate significantly in the non-randomized data but still
      possessed a false discovery rate as high as 50%. Adding a batch adjustment step
      before normalization further reduced the number of false positive markers while
      maintaining a similar number of true positive markers, which resulted in a false
      discovery rate of 32% to 48%, depending on the specific normalization method. We
      concluded the paper with some insights on possible causes of false discoveries to
      shed light on how to improve normalization for microRNA arrays. 

PMID- 24905457
TI  - MCP-1 as a potential target to inhibit the bone invasion by oral squamous cell
      carcinoma.
AB  - Bone invasion is a common complication of oral squamous cell carcinoma (OSCC),
      and this study sought to explore whether suppressed expression of monocyte
      chemotactic protein-1 (MCP-1) can be used to inhibit the bone invasion by OSCC.
      Strong staining of MCP-1 protein was observed from 10 archival blocks of OSCC by
      immunohistochemistry (IHC). Real-time PCR showed MCP-1 mRNA was highly expressed
      by OSCC cell lines (SCC25, HN5, and Tca8113), and SCC25 cells had the highest
      expression. An expression construct of a dominant negative variant of MCP-1 with
      7 amino acids truncated (7ND), in the vector pcDNA was used to transfect SCC25
      cells, and resultant stabilized SCC25 cells (SCC25-7ND) were generated by
      antibiotic selection. 10% conditioned media (CM, supernatant) of SCC25-7ND cells
      efficiently inhibited the formation of human osteoclasts grown from CD14(+)
      monocyte subpopulation, comparing with 10% CM of SCC25 cells. Further, cells of
      SCC25 or SCC25-7ND were injected onto the surface of calvariae of nude mice to
      establish an animal model of bone invasion by OSCC. H&E staining showed well
      differentiated OSCC was formed in both groups, tumour cells invading the bone
      while osteoclasts locating in typical resorption lacunae. TRAP staining indicated
      significantly fewer osteoclasts were found in calvariae with cells of SCC25-7ND
      in comparison to cells of SCC25. These data demonstrate the relevance of MCP-1
      with research on bone invasion by OSCC, and suggest the potential value of MCP-1
      as a target to inhibit this common complication.

PMID- 24905458
TI  - Small intestinal intraepithelial TCRgammadelta+ T lymphocytes are present in the
      premature intestine but selectively reduced in surgical necrotizing
      enterocolitis.
AB  - BACKGROUND: Gastrointestinal barrier immaturity predisposes preterm infants to
      necrotizing enterocolitis (NEC). Intraepithelial lymphocytes (IEL) bearing the
      unconventional T cell receptor (TCR) gammadelta (gammadelta IEL) maintain
      intestinal integrity and prevent bacterial translocation in part through
      production of interleukin (IL) 17. OBJECTIVE: We sought to study the development
      of gammadelta IEL in the ileum of human infants and examine their role in NEC
      pathogenesis. We defined the ontogeny of gammadelta IEL proportions in murine and
      human intestine and subjected tcrdelta-/- mice to experimental gut injury. In
      addition, we used polychromatic flow cytometry to calculate percentages of viable
      IEL (defined as CD3+ CD8+ CD103+ lymphocytes) and the fraction of gammadelta IEL
      in surgically resected tissue from infants with NEC and gestational age matched
      non-NEC surgical controls. RESULTS: In human preterm infants, the proportion of
      IEL was reduced by 66% in 11 NEC ileum resections compared to 30 non-NEC controls
      (p<0.001). While gammadelta IEL dominated over conventional alphabeta IEL early
      in gestation in mice and in humans, gammadelta IEL were preferential decreased in
      the ileum of surgical NEC patients compared to non-NEC controls (50% reduction,
      p<0.05). Loss of IEL in human NEC was associated with downregulation of the Th17
      transcription factor retinoic acid-related orphan nuclear hormone receptor C
      (RORC, p<0.001). TCRdelta-deficient mice showed increased severity of
      experimental gut injury (p<0.05) with higher TNFalpha expression but
      downregulation of IL17A. CONCLUSION: Complimentary mouse and human data suggest a
      role of gammadelta IEL in IL17 production and intestinal barrier production early
      in life. Specific loss of the gammadelta IEL fraction may contribute to NEC
      pathogenesis. Nutritional or pharmacological interventions to support gammadelta
      IEL maintenance in the developing small intestine could serve as novel strategies
      for NEC prevention.

PMID- 24905459
TI  - Additive effects of repetition and predictability during comprehension: evidence
      from event-related potentials.
AB  - Previous research has shown that neural responses to words during sentence
      comprehension are sensitive to both lexical repetition and a word's
      predictability in context. While previous research has often contrasted the
      effects of these variables (e.g. by looking at cases in which word repetition
      violates sentence-level constraints), little is known about how they work in
      tandem. In the current study we examine how recent exposure to a word and its
      predictability in context combine to impact lexical semantic processing. We
      devise a novel paradigm that combines reading comprehension with a recognition
      memory task, allowing for an orthogonal manipulation of a word's predictability
      and its repetition status. Using event-related brain potentials (ERPs), we show
      that word repetition and predictability have qualitatively similar and additive
      effects on the N400 amplitude. We propose that prior exposure to a word and
      predictability impact lexical semantic processing in an additive and independent
      fashion. 

PMID- 24905460
TI  - Itraconazole suppresses the growth of glioblastoma through induction of
      autophagy: involvement of abnormal cholesterol trafficking.
AB  - Glioblastoma is one of the most aggressive human cancers with poor prognosis, and
      therefore a critical need exists for novel therapeutic strategies for management
      of glioblastoma patients. Itraconazole, a traditional antifungal drug, has been
      identified as a novel potential anticancer agent due to its inhibitory effects on
      cell proliferation and tumor angiogenesis; however, the molecular mechanisms
      involved are still unclear. Here, we show that itraconazole inhibits the
      proliferation of glioblastoma cells both in vitro and in vivo. Notably, we
      demonstrate that treatment with itraconazole induces autophagic progression in
      glioblastoma cells, while blockage of autophagy markedly reverses the
      antiproliferative activities of itraconazole, suggesting an antitumor effect of
      autophagy in response to itraconazole treatment. Functional studies revealed that
      itraconazole retarded the trafficking of cholesterol from late endosomes and
      lysosomes to the plasma membrane by reducing the levels of SCP2, resulting in
      repression of AKT1-MTOR signaling, induction of autophagy, and finally inhibition
      of cell proliferation. Together, our studies provide new insights into the
      molecular mechanisms regarding the antitumor activities of itraconazole, and may
      further assist both the pharmacological investigation and rational use of
      itraconazole in potential clinical applications. 

PMID- 24905463
TI  - Rift migration explains continental margin asymmetry and crustal hyper-extension.
AB  - When continents break apart, continental crust and lithosphere are thinned until
      break-up is achieved and an oceanic basin is formed. The most remarkable and
      least understood structures associated with this process are up to 200 km wide
      areas of hyper-extended continental crust, which are partitioned between
      conjugate margins with pronounced asymmetry. Here we show, using high-resolution
      thermo-mechanical modelling, that hyper-extended crust and margin asymmetry are
      produced by steady state rift migration. We demonstrate that rift migration is
      accomplished by sequential, oceanward-younging, upper crustal faults, and is
      balanced through lower crustal flow. Constraining our model with a new South
      Atlantic plate reconstruction, we demonstrate that larger extension velocities
      may account for southward increasing width and asymmetry of these conjugate magma
      poor margins. Our model challenges conventional ideas of rifted margin evolution,
      as it implies that during rift migration large amounts of material are
      transferred from one side of the rift zone to the other.

PMID- 24905461
TI  - Testicular differentiation factor SF-1 is required for human spleen development.
AB  - The transcription factor steroidogenic factor 1 (SF-1; also known as NR5A1) is a
      crucial mediator of both steroidogenic and nonsteroidogenic tissue
      differentiation. Mutations within SF1 underlie different disorders of sexual
      development (DSD), including sex reversal, spermatogenic failure, ovarian
      insufficiency, and adrenocortical deficiency. Here, we identified a recessive
      mutation within SF1 that resulted in a substitution of arginine to glutamine at
      codon 103 (R103Q) in a child with both severe 46,XY-DSD and asplenia. The R103Q
      mutation decreased SF-1 transactivation of TLX1, a transcription factor that has
      been shown to be essential for murine spleen development. Additionally, the SF1
      R103Q mutation impaired activation of steroidogenic genes, without affecting
      synergistic SF-1 and sex-determining region Y (SRY) coactivation of the testis
      development gene SOX9. Together, our data provide evidence that SF-1 is required
      for spleen development in humans via transactivation of TLX1 and that mutations
      that only impair steroidogenesis, without altering the SF1/SRY transactivation of
      SOX9, can lead to 46,XY-DSD.

PMID- 24905464
TI  - Use of genetic data to infer population-specific ecological and phenotypic traits
      from mixed aggregations.
AB  - Many applications in ecological genetics involve sampling individuals from a
      mixture of multiple biological populations and subsequently associating those
      individuals with the populations from which they arose. Analytical methods that
      assign individuals to their putative population of origin have utility in both
      basic and applied research, providing information about population-specific life
      history and habitat use, ecotoxins, pathogen and parasite loads, and many other
      non-genetic ecological, or phenotypic traits. Although the question is initially
      directed at the origin of individuals, in most cases the ultimate desire is to
      investigate the distribution of some trait among populations. Current practice is
      to assign individuals to a population of origin and study properties of the trait
      among individuals within population strata as if they constituted independent
      samples. It seemed that approach might bias population-specific trait inference.
      In this study we made trait inferences directly through modeling, bypassing
      individual assignment. We extended a Bayesian model for population mixture
      analysis to incorporate parameters for the phenotypic trait and compared its
      performance to that of individual assignment with a minimum probability threshold
      for assignment. The Bayesian mixture model outperformed individual assignment
      under some trait inference conditions. However, by discarding individuals whose
      origins are most uncertain, the individual assignment method provided a less
      complex analytical technique whose performance may be adequate for some common
      trait inference problems. Our results provide specific guidance for method
      selection under various genetic relationships among populations with different
      trait distributions. 

PMID- 24905462
TI  - Expression and function analysis of mitotic checkpoint genes identifies TTK as a
      potential therapeutic target for human hepatocellular carcinoma.
AB  - The mitotic spindle checkpoint (SAC) genes have been considered targets of
      anticancer therapies. Here, we sought to identify the attractive mitotic spindle
      checkpoint genes appropriate for human hepatocellular carcinoma (HCC) therapies.
      Through expression profile analysis of 137 selected mitotic spindle checkpoint
      genes in the publicly available microarray datasets, we showed that 13 genes were
      dramatically up-regulated in HCC tissues compared to normal livers and adjacent
      non-tumor tissues. A role of the 13 genes in proliferation was evaluated by
      knocking them down via small interfering RNA (siRNA) in HCC cells. As a result,
      several mitotic spindle checkpoint genes were required for maintaining the
      proliferation of HCC cells, demonstrated by cell viability assay and soft agar
      colony formation assay. Then we established sorafenib-resistant sublines of HCC
      cell lines Huh7 and HepG2. Intriguingly, increased TTK expression was
      significantly associated with acquired sorafenib-resistance in Huh7, HepG2 cells.
      More importantly, TTK was observably up-regulated in 46 (86.8%) of 53 HCC
      specimens. A series of in vitro and in vivo functional experiment assays showed
      that TTK overexpression promoted cell proliferation, anchor-dependent colony
      formation and resistance to sorafenib of HCC cells; TTK knockdown restrained cell
      growth, soft agar colony formation and resistance to sorafenib of HCC cells.
      Collectively, TTK plays an important role in proliferation and sorafenib
      resistance and could act as a potential therapeutic target for human
      hepatocellular carcinoma. 

PMID- 24905465
TI  - Impact of Copula Directional Specification on Multi-Trial Evaluation of Surrogate
      End Points.
AB  - Evaluation of surrogate end points using patient-level data from multiple trials
      is the gold standard, where multi-trial copula models are used to quantify both
      patient-level and trial-level surrogacy. While limited consideration has been
      given in the literature to copula choice (e.g., Clayton), no prior consideration
      has been given to direction of implementation (via survival vs. distribution
      functions). We demonstrate that even with the "correct" copula family,
      directional misspecification leads to biased estimates of patient-level and trial
      level surrogacy. We illustrate with a simulation study and a reanalysis of
      disease-free survival as a surrogate for overall survival in early stage colon
      cancer. 

PMID- 24905467
TI  - Contributions of dental colour to the physical attractiveness stereotype.
AB  - Dental appearance may play a key role on the way we develop a first impression of
      another person. To test whether relatively minor changes in the lightness of
      tooth colour would influence the perceived social appeal (social, intellectual,
      psychological and relational abilities) of an unknown male and unknown female,
      this cross-sectional study was performed on 555 Spanish adults. The two major
      independent variables related to the photograph were tooth lightness (computer
      derived), divided into three levels that included lightened teeth, natural teeth
      and darkened teeth, and the gender of the observed face. Moreover, six
      independent variables related to the observer were assessed (age, gender,
      educational level, place of residence, frequency of brushing and self-reported
      health status). The dependent variables were scored on five-point Likert scales
      designed to quantify four domains (social, intellectual, psychological and
      relationship competences) of the Social Appeal Scale (SAS). Tooth lightness
      influences the perception of social appeal in all dimensions, as darkened smiles
      received significantly poorer scores than natural-colour smiles, but these were
      also worse than lightened smiles. A logistic regression analysis revealed that
      the major predictor of social appeal was tooth lightness, and for each increment
      in lightness (from darkened to lightened smiles), the odds ratio (OR) of positive
      values being perceived increased significantly in all items (from 2.3 in
      Popularity to 6.9 in Happiness). A perceptible change in dental lightness is the
      strongest factor associated with the dental attractiveness stereotype, affecting
      significantly the 12 traits assessed, but mainly the Happiness, Social Relations
      and Academic Performance. 

PMID- 24905466
TI  - Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma
      progression in vitro and in vivo.
AB  - Insulin-like-factor-binding-protein 3 (IGFBP-3) is known to modulate the activity
      of insulin-like growth factors (IGFs) besides having a number of IGF-independent
      effects on cell growth and survival. IGFBP-3 has been reported to decrease
      significantly in the blood serum of patients affected by certain cancers. In the
      present work, we have evaluated the levels of IGFBP-3 in the blood serum and
      tissues of patients affected by cutaneous melanoma, showing that loss of IGFBP-3
      from both is strongly correlated with disease progression and reduced survival.
      In vitro treatment with IGFBP-3 of human and murine metastatic melanoma cell
      lines specifically inhibited the cells' migratory and invasive behaviour,
      inducing up-regulation of melanocytic differentiation markers such as tyrosinase
      activity and melanin content. A molecular analysis of the cellular pathways
      transducing the effect of IGFBP-3 implicated the Akt-GSK3beta axis. Moreover,
      administration of IGFBP-3 in vivo to SCID mice inoculated with human metastatic
      melanoma cells strongly reduced or completely inhibited tumor growth. In summary,
      IGFBP-3 appears to exert a specific inhibitory effect on melanoma growth and
      dissemination, suggesting that it may qualify as a useful therapeutic agent in
      melanomas and perhaps other cancers, at the least as a valid adjuvant therapy
      during treatment with conventional anti-tumoral drugs. 

PMID- 24905468
TI  - FFBSKAT: fast family-based sequence kernel association test.
AB  - The kernel machine-based regression is an efficient approach to region-based
      association analysis aimed at identification of rare genetic variants. However,
      this method is computationally complex. The running time of kernel-based
      association analysis becomes especially long for samples with genetic (sub)
      structures, thus increasing the need to develop new and effective methods,
      algorithms, and software packages. We have developed a new R-package called fast
      family-based sequence kernel association test (FFBSKAT) for analysis of
      quantitative traits in samples of related individuals. This software implements a
      score-based variance component test to assess the association of a given set of
      single nucleotide polymorphisms with a continuous phenotype. We compared the
      performance of our software with that of two existing software for family-based
      sequence kernel association testing, namely, ASKAT and famSKAT, using the Genetic
      Analysis Workshop 17 family sample. Results demonstrate that FFBSKAT is several
      times faster than other available programs. In addition, the calculations of the
      three-compared software were similarly accurate. With respect to the available
      analysis modes, we combined the advantages of both ASKAT and famSKAT and added
      new options to empower FFBSKAT users. The FFBSKAT package is fast, user-friendly,
      and provides an easy-to-use method to perform whole-exome kernel machine-based
      regression association analysis of quantitative traits in samples of related
      individuals. The FFBSKAT package, along with its manual, is available for free
      download at http://mga.bionet.nsc.ru/soft/FFBSKAT/. 

PMID- 24905469
TI  - Reaction and detection click in high-voltage assisted laser desorption ionization
      mass spectrometry.
AB  - A click reaction (copper-catalyzed azide-alkyne cycloaddition) catalyzed by
      "naked" copper ions (without ligands) generated in situ from a copper substrate
      by laser ablation in a high-voltage assisted laser desorption/ionization (HALDI)
      ion source is demonstrated. 

PMID- 24905470
TI  - Effect of hydrofracking fluid on colloid transport in the unsaturated zone.
AB  - Hydraulic fracturing is expanding rapidly in the US to meet increasing energy
      demand and requires high volumes of hydrofracking fluid to displace natural gas
      from shale. Accidental spills and deliberate land application of hydrofracking
      fluids, which return to the surface during hydrofracking, are common causes of
      environmental contamination. Since the chemistry of hydrofracking fluids favors
      transport of colloids and mineral particles through rock cracks, it may also
      facilitate transport of in situ colloids and associated pollutants in unsaturated
      soils. We investigated this by subsequently injecting deionized water and
      flowback fluid at increasing flow rates into unsaturated sand columns containing
      colloids. Colloid retention and mobilization was measured in the column effluent
      and visualized in situ with bright field microscopy. While <5% of initial
      colloids were released by flushing with deionized water, 32-36% were released by
      flushing with flowback fluid in two distinct breakthrough peaks. These peaks
      resulted from 1) surface tension reduction and steric repulsion and 2) slow
      kinetic disaggregation of colloid flocs. Increasing the flow rate of the flowback
      fluid mobilized an additional 36% of colloids, due to the expansion of water
      filled pore space. This study suggests that hydrofracking fluid may also
      indirectly contaminate groundwater by remobilizing existing colloidal pollutants.

PMID- 24905471
TI  - Toward enabling large-scale open-shell equation-of-motion coupled cluster
      calculations: triplet states of beta-carotene.
AB  - In this paper we discuss the application of novel parallel implementation of the
      coupled cluster (CC) and equation-of-motion coupled cluster methods (EOMCC) in
      calculations of excitation energies of triplet states in beta-carotene.
      Calculated excitation energies are compared with experimental data, where
      available. We also provide a detailed description of the new parallel algorithms
      for iterative CC and EOMCC models involving singles and doubles excitations. 

PMID- 24905472
TI  - Pharmacophore generation of 2-substituted benzothiazoles as AdeABC efflux pump
      inhibitors in A. baumannii.
AB  - RND family efflux pumps are important for multidrug resistance in Gram-negative
      bacteria. To date no efflux pump inhibitors for clinical use have been found, so
      developing the specific inhibitors of this pump system will be beneficial for the
      treatment of infections caused by these multidrug-resistant pathogens. A set of
      BSN-coded 2-substituted benzothiazoles were tested alone and in combination with
      ciprofloxacin (CIP) against the RND family efflux pump AdeABC overexpressor
      Acinetobacter baumannii SbMox-2 strain. The results indicated that the BSN
      compounds did not have antimicrobial activity when tested alone. However, if they
      were applied in combination with CIP, it was observed that the antibiotic had
      antimicrobial activity against the tested pathogen, possessing a minimum
      inhibitory concentration value that could be utilized in clinical treatment. A 3D
      common features pharmacophore model was applied by using the HipHop method and
      the generated pharmacophore hypothesis revealed that the hydrogen bond acceptor
      property of nitrogen in the thiazole ring and the oxygen of the amide substituted
      at the second position of the benzothiazole ring system were significant for
      binding to the target protein. Moreover, three hydrophobic aromatic features were
      found to be essential for inhibitory activity. 

PMID- 24905473
TI  - Epidermal growth factor inhibits transforming growth factor-beta-induced
      fibrogenic differentiation marker expression through ERK activation.
AB  - Transforming growth factor-beta (TGF-beta) signaling plays an important and
      complex role in renal fibrogenesis. The seemingly simple TGF-beta/Smad cascade is
      intensively regulated at several levels, including crosstalk with other signaling
      pathways. Epidermal growth factor (EGF) is a potent mitogen for epithelial cells
      and is elevated in diseased kidneys. In this study, we examined its effect on TGF
      beta-induced fibrotic changes in human proximal tubular epithelial cells.
      Simultaneous treatment with EGF specifically inhibited basal and TGF-beta-induced
      type-I collagen and alpha-smooth muscle actin (alphaSMA) expression at both mRNA
      and protein levels. These effects were prevented by inhibition of either the EGF
      receptor kinase or its downstream MEK kinase but not by blockade of either the
      JNK or PI3K pathway. Overexpression of a constitutively active MEK1 construct
      mimicked the inhibitory effect of EGF. Further, EGF suppressed Smad
      transcriptional activities, as shown by reduced activation of ARE-luc and SBE
      luc. Both reductions were prevented by MEK inhibition. However, EGF did not block
      Smad2 or Smad3 phosphorylation by TGF-beta, or Smad2/3 nuclear import. Finally
      EGF induced the phosphorylation and expression of TGIF, a known TGF-beta/Smad
      repressor. Both the phosphorylation and the induction were blocked by a MEK
      inhibitor. Overexpression of TGIF abolished TGF-beta-induced alphaSMA promoter
      activity. Together these results suggest that EGF inhibits two TGF-beta
      stimulated markers of EMT through EGF receptor tyrosine kinase and downstream ERK
      activation, but not through PI3K or JNK. The inhibition results from effector
      mechanisms downstream of Smads, and most likely involves the transcriptional
      repressor, TGIF.

PMID- 24905476
TI  - Quantifying ligand-receptor interactions for gorge-spanning acetylcholinesterase
      inhibitors for the treatment of Alzheimer's disease.
AB  - There is a need for continued development of acetylcholinesterase (AChE)
      inhibitors that could prolong the life of acetylcholine in the synaptic cleft and
      also prevent the aggregation of amyloid peptides associated with Alzheimer's
      disease. The lack of a 3D-QSAR model which specifically deconvulates the type of
      interactions and quantifies them in terms of energies has motivated us to report
      a CoRIA model vis-a-vis the standard 3D-QSAR methods, CoMFA and CoMSIA. The CoRIA
      model was found to be statistically superior to the CoMFA and CoMSIA models and
      it could efficiently extract key residues involved in ligand recognition and
      binding to AChE. These interactions were quantified to gauge the magnitude of
      their contribution to the biological activity. In order to validate the CoRIA
      model, a pharmacophore map was first constructed and then used to virtually
      screen public databases, from which novel scaffolds were cherry picked that were
      not present in the training set. The biological activities of these novel
      molecules were then predicted by the CoRIA, CoMFA, and CoMSIA models. The hits
      identified were purchased and their biological activities were measured by the
      Ellman's method for AChE inhibition. The predicted activities are in unison with
      the experimentally measured biological activities. 

PMID- 24905477
TI  - Development of a self-administered questionnaire to assess the psychological
      competencies for surviving a disaster.
AB  - OBJECTIVE: To find the psychological competencies for surviving a disaster and
      develop a self-report questionnaire to assess them. METHODS: Interviews with 16
      earthquake survivors and 16 fire fighters followed by qualitative analysis were
      used to find psychological competencies. Formation of the item pool, a pilot
      study among 20 college teachers and students, a series of principal component
      analyses for the data from 345 college students, and a confirmatory factor
      analysis for the data from 307 participants with various occupations were used to
      develop the Psychological Competencies for Surviving a Disaster Questionnaire
      (PCSDQ). RESULTS: We found 4 psychological competencies: risk perception of a
      disaster, disaster knowledge and self-relief skills, low fear in a disaster, and
      sense of control over a disaster. The 24-item PCSDQ assessed these psychological
      competencies. The Cronbach alpha of PCSDQ subscales ranged from .75 to .87.
      CONCLUSIONS: The psychological competencies for surviving a disaster were found
      to be risk perception of a disaster, disaster knowledge and self-relief skills,
      low fear in a disaster, and sense of control over a disaster. Using the PCSDQ to
      assess a person's psychological competencies for disaster survival will make it
      possible to provide that person with an individualized and targeted disaster self
      relief education and/or training program.

PMID- 24905474
TI  - The protein tyrosine phosphatase PTPN22 controls forkhead box protein 3 T
      regulatory cell induction but is dispensable for T helper type 1 cell
      polarization.
AB  - Protein tyrosine phosphatases (PTPs) regulate T cell receptor (TCR) signalling
      and thus have a role in T cell differentiation. Here we tested whether the
      autoimmune predisposing gene PTPN22 encoding for a PTP that inhibits TCR
      signalling affects the generation of forkhead box protein 3 (FoxP3)(+) T
      regulatory (Treg ) cells and T helper type 1 (Th1) cells. Murine CD4(+) T cells
      isolated from Ptpn22 knock-out (Ptpn22(KO) ) mice cultured in Treg cell
      polarizing conditions showed increased sensitivity to TCR activation compared to
      wild-type (WT) cells, and subsequently reduced FoxP3 expression at optimal-to
      high levels of activation. However, at lower levels of TCR activation, Ptpn22(KO)
      CD4(+) T cells showed enhanced expression of FoxP3. Similar experiments in humans
      revealed that at optimal levels of TCR activation PTPN22 knock-down by specific
      oligonucleotides compromises the differentiation of naive CD4(+) T cells into
      Treg cells. Notably, in vivo Treg cell conversion experiments in mice showed
      delayed kinetic but overall increased frequency and number of Treg cells in the
      absence of Ptpn22. In contrast, the in vitro and in vivo generation of Th1 cells
      was comparable between WT and Ptpn22(KO) mice, thus suggesting PTPN22 as a FoxP3
      specific regulating factor. Together, these results propose PTPN22 as a key
      factor in setting the proper threshold for FoxP3(+) Treg cell differentiation.

PMID- 24905478
TI  - On Comparison of Clustering Methods for Pharmacoepidemiological Data.
AB  - The high consumption of psychotropic drugs is a public health problem. Rigorous
      statistical methods are needed to identify consumption characteristics in post
      marketing phase. Agglomerative hierarchical clustering (AHC) and latent class
      analysis (LCA) can both provide clusters of subjects with similar
      characteristics. The objective of this study was to compare these two methods in
      pharmacoepidemiology, on several criteria: number of clusters, concordance,
      interpretation, and stability over time. From a dataset on bromazepam
      consumption, the two methods present a good concordance. AHC is a very stable
      method and it provides homogeneous classes. LCA is an inferential approach and
      seems to allow identifying more accurately extreme deviant behavior. 

PMID- 24905479
TI  - Co-existence of uterine myomas and endometriosis in women undergoing laparoscopic
      myomectomy: risk factors and surgical implications.
AB  - STUDY OBJECTIVE: To investigate the prevalence of and explore risk factors for
      the coexistence of uterine myomas and endometriosis and to assess operative
      outcomes during laparoscopic myomectomy. DESIGN: Retrospective cohort study
      (Canadian Task Force classification II-2). SETTING: Tertiary referral center in
      London, England. PATIENTS: Two hundred twelve women undergoing laparoscopic
      myomectomy to treat symptomatic uterine myomas. INTERVENTION: Laparoscopic
      myomectomy. MEASUREMENTS AND MAIN RESULTS: Coexisting myomas and endometriosis
      were identified in 21.2% of patients. Endometriosis was more common in those with
      subfertility (44% vs 25.7%; p = .02) and less common in those with bleeding
      disorders (20% vs 45%; p = .003). Parity, location of myoma, and race/ethnicity
      affected risk of endometriosis, whereas size and number of myomas did not. Of
      patients with endometriosis, 42% underwent surgical treatment of endometriosis
      during myomectomy. Significantly more patients with endometriosis also underwent
      ovarian cystectomy than did those without endometriosis (15.6% vs 3%; p = .004).
      Operative time was similar in both groups (109.6 minutes vs 116.4 minutes; p =
      .83), as was estimated blood loss (271 mL vs 327 mL; p = .16). CONCLUSIONS: A
      diagnosis of concomitant endometriosis should be considered, in particular in
      patients with subfertility and pain. This enables optimal preoperative counseling
      and consent for potential additional procedures such as treatment of
      endometriosis or ovarian cystectomy.

PMID- 24905480
TI  - A monomer-dimer nanoswitch that mimics the working principle of the SARS-CoV
      3CLpro enzyme controls copper-catalysed cyclopropanation.
AB  - A triangular framework with a terpyridine and shielded phenanthroline at its
      termini constitutes an open/close nanoswitch that is toggled by chemical inputs.
      In the presence of copper(I) ions, the open triangular framework (OPEN-I) firmly
      closes to a catalytically inactive heteroleptic [Cu(phen)(terpy)](+) complex
      (CLOSE). Reversible switching between CLOSE and OPEN-I states was demonstrated by
      successive addition and removal of Cu(+). In contrast, after addition of iron(II)
      ions to the CLOSE state a bishomoleptic dimeric [Fe(terpy)2](2+) complex is
      formed with the copper(I) ions placed in the phenanthroline cavities (OPEN-II).
      Due to its coordinatively unsaturated [Cu(Phen)](+) sites the dimeric iron
      complex is able to serve as a catalyst in the cyclopropanation of Z-cyclooctene
      using ethyl diazoacetate.

PMID- 24905481
TI  - The use of linked activity schedules to teach children with autism to play hide
      and-seek.
AB  - Linked activity schedules were used to establish appropriate game play in
      children with autism during a game of hide-and-seek. All 6 participants
      demonstrated acquisition of appropriate play skills in the presence of the
      activity schedules and maintained responding during subsequent phases. When the
      schedules were removed, responding decreased to baseline levels, demonstrating
      that the schedules controlled responding. Implications for future research on the
      use of activity schedules to teach social behavior are discussed. 

PMID- 24905483
TI  - Characterization of a novel Conus bandanus conopeptide belonging to the M
      superfamily containing bromotryptophan.
AB  - A novel conotoxin (conopeptide) was biochemically characterized from the crude
      venom of the molluscivorous marine snail, Conus bandanus (Hwass in Bruguiere,
      1792), collected in the south-central coast of Vietnam. The peptide was
      identified by screening bromotryptophan from chromatographic fractions of the
      crude venom. Tandem mass spectrometry techniques were used to detect and localize
      different post-translational modifications (PTMs) present in the BnIIID
      conopeptide. The sequence was confirmed by Edman's degradation and mass
      spectrometry revealing that the purified BnIIID conopeptide had 15 amino acid
      residues, with six cysteines at positions 1, 2, 7, 11, 13, and 14, and three
      PTMs: bromotryptophan, gamma-carboxy glutamate, and amidated aspartic acid, at
      positions "4", "5", and "15", respectively. The BnIIID peptide was synthesized
      for comparison with the native peptide. Homology comparison with conopeptides
      having the III-cysteine framework (-CCx1x2x3x4Cx1x2x3Cx1CC-) revealed that BnIIID
      belongs to the M-1 family of conotoxins. This is the first report of a member of
      the M-superfamily containing bromotryptophan as PTM. 

PMID- 24905484
TI  - Chromomycins A2 and A3 from marine actinomycetes with TRAIL resistance-overcoming
      and Wnt signal inhibitory activities.
AB  - A biological screening study of an actinomycetes strain assembly was conducted
      using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea
      sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture
      broth, which exhibited cytotoxicity, led to the isolation of chromomycins A2 (1)
      and A3 (2). 1 and 2 showed potent cytotoxicity against the human gastric
      adenocarcinoma (AGS) cell line (IC50 1; 1.7 and 2; 22.1 nM), as well as strong
      inhibitory effects against TCF/beta-catenin transcription (IC50 1; 1.8 and 2;
      15.9 nM). 2 showed the ability to overcome tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL) resistance. To the best of our knowledge, the
      effects of chromomycins A2 (1) and A3 (2) on TRAIL resistance-overcoming
      activity, and on the Wnt signaling pathway, have not been reported previously.
      Thus, 1 and 2 warrant potential drug lead studies in relation to TRAIL-resistant
      and Wnt signal-related diseases and offer potentially useful chemical probes for
      investigating TRAIL resistance and the Wnt signaling pathway. 

PMID- 24905482
TI  - Metabolomic tools for secondary metabolite discovery from marine microbial
      symbionts.
AB  - Marine invertebrate-associated symbiotic bacteria produce a plethora of novel
      secondary metabolites which may be structurally unique with interesting
      pharmacological properties. Selection of strains usually relies on literature
      searching, genetic screening and bioactivity results, often without considering
      the chemical novelty and abundance of secondary metabolites being produced by the
      microorganism until the time-consuming bioassay-guided isolation stages. To fast
      track the selection process, metabolomic tools were used to aid strain selection
      by investigating differences in the chemical profiles of 77 bacterial extracts
      isolated from cold water marine invertebrates from Orkney, Scotland using liquid
      chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic
      resonance (NMR) spectroscopy. Following mass spectrometric analysis and
      dereplication using an Excel macro developed in-house, principal component
      analysis (PCA) was employed to differentiate the bacterial strains based on their
      chemical profiles. NMR 1H and correlation spectroscopy (COSY) were also employed
      to obtain a chemical fingerprint of each bacterial strain and to confirm the
      presence of functional groups and spin systems. These results were then combined
      with taxonomic identification and bioassay screening data to identify three
      bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio
      splendidus strain LGP32, to prioritize for scale-up based on their chemically
      interesting secondary metabolomes, established through dereplication and
      interesting bioactivities, determined from bioassay screening. 

PMID- 24905486
TI  - Polycystic kidney disease in a Neva Masquerade cat.

PMID- 24905485
TI  - Cespitulones A and B, cytotoxic diterpenoids of a new structure class from the
      soft coral Cespitularia taeniata.
AB  - Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts
      of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented
      bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and
      between C-20 and C-11. Their structures were elucidated on the basis of extensive
      spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against
      human medulloblastoma and colon adenocarcinoma cancer cells. 

PMID- 24905487
TI  - Airborne particulates (PM10) and tracheal mucus: A case-control study at an
      American Thoroughbred racetrack.
AB  - REASONS FOR PERFORMING STUDY: Particle mapping within stalls has demonstrated a
      relationship between particulate concentrations and visible accumulations of
      tracheal mucus. However, measurement of breathing zone particulate
      concentrations, which is the most accurate way to measure exposure, has not been
      performed to determine the relationship between exposures and accumulations of
      tracheal mucus sufficient to affect performance. OBJECTIVES: To compare breathing
      zone particulate exposures between horses with tracheal mucus scores (MS)
      previously demonstrated to affect performance (MS>=2) and those without (MS = 0)
      visible tracheal mucus. STUDY DESIGN: Case-control study. METHODS: We
      endoscopically examined 649 Thoroughbred racehorses over 7 months and selected
      113 age-matched cases and controls based on the presence (MS>=2) or absence (MS =
      0) of tracheal mucus, respectively. Inflammatory cell numbers in tracheal lavage
      were also determined. Breathing zone monitors recorded particulate exposure
      during 3 time periods (mid-day, evening and overnight). Total recording time
      averaged 17.5 h/horse. RESULTS: The overall prevalence of MS>=2 in the observed
      stables was 23%. Breathing zone particular matter (PM10) concentrations were very
      similar to previously reported ambient concentrations. During the evening and
      overnight, cases had significantly higher breathing zone PM10 concentrations and
      neutrophil counts than controls. Inflammatory cell counts were associated with
      average PM10 concentrations throughout the day. CONCLUSIONS: Breathing zone
      particulate concentrations are associated with MS>=2 and inflammatory cell
      numbers. If breathing zone particulate exposures are predominantly influenced by
      ambient PM concentrations, racing stable management practices to reduce particle
      exposures should greatly reduce the prevalence of tracheal mucus.

PMID- 24905488
TI  - Sleep disorders among French anaesthesiologists and intensivists working in
      public hospitals: a self-reported electronic survey.
AB  - BACKGROUND: Sleep disorders can affect the health of physicians and patient
      outcomes. OBJECTIVES: To determine the prevalence of sleep disorders among French
      anaesthesiologists and intensivists working in a public hospital. DESIGN: A cross
      sectional survey. SETTING: Anaesthesiologists and intensivists working in French
      public hospitals. MAIN OUTCOME MEASURES: Sleep quality was assessed using the
      Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) was
      used to assess the degree of excessive daytime sleepiness. RESULTS: Among 1504
      responders, 677 (45%) physicians reported sleep disorders. The independent
      factors associated with sleep disorders were reporting of sleep disorders [odds
      ratio (OR) 12.04, 95% CI (95% confidence interval) 8.89 to 16.46], sleep time
      less than 7 h (OR 8.86, 95% CI 6.50 to 12.20), work stress (OR 2.04, 95% CI 1.49
      to 2.83), stress at home (OR 1.77, 95% CI 1.24 to 2.53), anxiolytic use (OR 3.69,
      95% CI 2.23 to 6.25), psychotropic drug use (OR 3.91, 95% CI 1.51 to 11.52) and
      excessive daytime sleepiness (OR 1.81, 95% CI 1.34 to 2.45). Six hundred and
      seventy-six (44%) responders reported excessive daytime sleepiness during their
      professional activity. The independent factors associated with excessive daytime
      sleepiness were female sex (OR 1.86, 95% CI 1.49 to 2.34), tea consumption (OR
      1.47, 95% CI 1.14 to 1.91), regular practice of nap (OR 1.68, 95% CI 1.34 to
      2.09), stress at home (OR 1.31, 95% CI 1.02 to 1.68), more than four extended
      work shifts monthly (OR 1.25, 95% CI 1.01 to 1.56) and sleep disorders (OR 1.73,
      95% CI 1.31 to 2.29). Reporting sleep disorder duration and a sleep time less
      than 7 h were the two major risk factors for sleep disorders. Female sex was the
      major risk factor for excessive daytime sleepiness. CONCLUSION: French
      anaesthesiologists did not report more sleep disorders than the general
      population, but their alertness is impaired by a factor of two.

PMID- 24905489
TI  - Are postoperative behavioural changes after adenotonsillectomy in children
      influenced by the type of anaesthesia?: A randomised clinical study.
AB  - BACKGROUND: Negative postoperative behavioural changes (NPOBCs) are very frequent
      in children after surgery and general anaesthesia. If they persist, emotional and
      cognitive development may be affected significantly. OBJECTIVE: To assess whether
      the choice of different anaesthetic techniques for adenotonsillectomy may impact
      upon the incidence of NPOBC in repeated measurements. DESIGN: A randomised,
      controlled, parallel-group trial. SETTING: University Hospital Split, Croatia.
      PATIENTS: Sixty-four children (aged 6 to 12 years, ASA 1 to 2) undergoing
      adenotonsillectomy assigned into one of two groups: sevoflurane (S) (n = 32) or
      total intravenous anaesthesia (TIVA) (n = 32). INTERVENTIONS: Permuted-block
      randomisation with random block sizes of 4, 6 and 8, administering anaesthesia,
      and evaluation of NPOBC with the Post Hospitalization Behavior Questionnaire
      (PHBQ: 27 items describing six subscales). The PHBQ was filled out by parents at
      postoperative days (POD) 1, 3, 7 and 14, and 6 months after surgery. MAIN OUTCOME
      MEASURES: Differences in numbers of NPOBCs between two anaesthesia techniques,
      and NPOBC analysis by subscales. RESULTS: The prevalence of at least one NPOBC
      after surgery ranged from a maximum of 80% [95% confidence interval (CI) 71 to
      90%] on POD 1 to a minimum of 43% (95% CI 31 to 56%) 6 months after surgery.
      Absolute risk reduction for at least one NPOBC in the TIVA group compared with
      the S group increased from 0.24 on POD 1 to 0.55 6 months after surgery. The
      number of NPOBCs was also lower in the TIVA group [median 5, interquartile range
      (IQR) 2 to 10] than in the S group (median 22, IQR 10 to 32) (P < 0.001). The
      overall number of NPOBCs within PHBQ subscales was significantly lower in the
      TIVA group than in the S group. The largest difference in the number of NPOBCs
      between groups was observed for the separation anxiety subscale (mean 5, 95% CI 1
      to 9; P < 0.001) followed by the general anxiety subscale (mean 4, 95% CI 3 to 5;
      P < 0.001) and apathy/withdrawal subscale (mean 3, 95% CI 1 to 5; P < 0.001).
      CONCLUSION: The prevalence of NPOBC after elective adenotonsillectomy in 6 to 12
      year-old children was very high (80%). The choice of anaesthetic technique for
      adenotonsillectomy in children influenced the incidence and type of NPOBC.
      Sevoflurane/nitrous oxide anaesthesia was associated with more frequent and
      prolonged NPOBCs than TIVA, especially in the separation anxiety, general anxiety
      and withdrawal/apathy subscales.

PMID- 24905490
TI  - Apolipoprotein H expression is associated with IL28B genotype and viral clearance
      in hepatitis C virus infection.
AB  - BACKGROUND & AIMS: HCV requires host lipid metabolism for replication, and
      apolipoproteins have been implicated in the response to treatment. METHODS: We
      examined plasma apolipoprotein concentrations in three cohorts of patients: mono
      infected patients with symptomatic acute hepatitis C (aHCV); those undergoing
      treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being
      treated for their chronic hepatitis C. We also evaluated associations between
      apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral
      clearance. RESULTS: Plasma apolipoprotein H (ApoH) levels were significantly
      higher in patients who achieved spontaneous clearance or responded to pegylated
      interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860
      CC SNP correlated with the plasma concentration of ApoH in all three cohorts.
      Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate
      analysis. Additional multivariate analysis revealed that the association between
      IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance,
      suggesting that both belong to the same biological pathway to clearance. The
      association between IL28B CC SNP and ApoH was not observed in healthy
      individuals, suggesting that early post-infection events trigger differential
      ApoH expression in an IL28B allele dependent manner. CONCLUSIONS: This
      relationship identifies ApoH as the first induced protein quantitative trait
      associated with IL28B, and characterises a novel host factor implicated in HCV
      clearance.

PMID- 24905491
TI  - Chronic HDV/HBV co-infection: predictors of disease stage---a case series of HDV
      3 patients.
AB  - BACKGROUND & AIMS: Chronic HDV/HBV co-infection is perhaps the most intriguing
      amongst all viral hepatitis. Only few studies focus deeply on this topic,
      particularly with patients infected with HDV-3. This study aimed to identify
      predictors of advanced disease, examining a cross-sectional data of 64 patients.
      METHODS: Histological grading was used to characterize the disease stages and
      viral loads were tested as predictors of necroinflammatory activity and fibrosis.
      RESULTS: We identified three HDV/HBV co-infection patterns: patients with
      predominant HDV replication (56.3%), patients with similar viral loads of both
      viruses (40.6%), and patients with predominant HBV replication (3.1%). Mean HDV
      RNA showed a positive trend regarding inflammatory activity and grade of
      fibrosis. HDV viral load correlated positively with serum levels of liver enzymes
      and inversely with platelets count. HBV viral load showed no correlation with any
      of the above parameters. Advanced fibrosis was associated with age, splenomegaly,
      and HDV viral load of more than 2 log10. Multiple logistic regression confirmed
      the independent effect of HDV viral predominance. Advanced necroinflammatory
      activity was independently associated with HDV viral load and splenomegaly.
      CONCLUSIONS: HDV may possibly play an important and direct role in the
      establishment of necroinflammatory activity and fibrosis. Data show an indigenous
      HDV genotype, HDV-3, similar to those described in the Amazon region.

PMID- 24905492
TI  - Restoration of HCV-specific CD8+ T cell function by interferon-free therapy.
AB  - BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is characterised by
      a failure of virus-specific CD8+ T cells that is mainly caused by viral escape
      and T cell exhaustion. Constant antigen stimulation has been suggested to
      contribute to HCV-specific CD8+ T cell exhaustion. However, IFN-based therapies
      failed to recover HCV-specific CD8+ T cell function suggesting that the damage to
      CD8+ T cells may be permanent even after antigen removal. It was therefore the
      objective of this study to analyse the impact of inhibition of ongoing viral
      replication by IFN-free therapy with direct acting antivirals (DAA) on the
      phenotype and function of HCV-specific CD8+ T cells. METHODS: Virus-specific CD8+
      T cells obtained from a patient cohort of 51 previously untreated chronically
      infected patients undergoing IFN-free therapy with a combination of faldaprevir
      (a protease inhibitor) and deleobuvir (a non-nucleoside polymerase inhibitor)
      with or without ribavirin were analysed ex vivo and after in vitro expansion at
      baseline, wk4, wk 12, and after treatment. RESULTS: Our results show the rapid
      restoration of proliferative HCV-specific CD8+ T cells in the majority of
      patients with SVR12 within 4 weeks of therapy suggesting that IFN-free therapy
      mediated antigen removal may restore CD8+ T cell function. CONCLUSIONS: This
      study indicates a specific restoration of proliferative HCV-specific CD8+ T cells
      under IFN-free therapy. This is in contrast to PegIFN-based therapies that have
      been shown not to restore T cell function during and after chronic infection.

PMID- 24905493
TI  - Use of artificial intelligence as an innovative donor-recipient matching model
      for liver transplantation: results from a multicenter Spanish study.
AB  - BACKGROUND & AIMS: There is an increasing discrepancy between the number of
      potential liver graft recipients and the number of organs available. Organ
      allocation should follow the concept of benefit of survival, avoiding human
      innate subjectivity. The aim of this study is to use artificial-neural-networks
      (ANNs) for donor-recipient (D-R) matching in liver transplantation (LT) and to
      compare its accuracy with validated scores (MELD, D-MELD, DRI, P-SOFT, SOFT, and
      BAR) of graft survival. METHODS: 64 donor and recipient variables from a set of
      1003 LTs from a multicenter study including 11 Spanish centres were included. For
      each D-R pair, common statistics (simple and multiple regression models) and ANN
      formulae for two non-complementary probability-models of 3-month graft-survival
      and -loss were calculated: a positive-survival (NN-CCR) and a negative-loss (NN
      MS) model. The NN models were obtained by using the Neural Net Evolutionary
      Programming (NNEP) algorithm. Additionally, receiver-operating-curves (ROC) were
      performed to validate ANNs against other scores. RESULTS: Optimal results for NN
      CCR and NN-MS models were obtained, with the best performance in predicting the
      probability of graft-survival (90.79%) and -loss (71.42%) for each D-R pair,
      significantly improving results from multiple regressions. ROC curves for 3
      months graft-survival and -loss predictions were significantly more accurate for
      ANN than for other scores in both NN-CCR (AUROC-ANN=0.80 vs. -MELD=0.50; -D
      MELD=0.54; -P-SOFT=0.54; -SOFT=0.55; -BAR=0.67 and -DRI=0.42) and NN-MS (AUROC
      ANN=0.82 vs. -MELD=0.41; -D-MELD=0.47; -P-SOFT=0.43; -SOFT=0.57, -BAR=0.61 and 
      DRI=0.48). CONCLUSIONS: ANNs may be considered a powerful decision-making
      technology for this dataset, optimizing the principles of justice, efficiency and
      equity. This may be a useful tool for predicting the 3-month outcome and a
      potential research area for future D-R matching models.

PMID- 24905494
TI  - Clinical significance of a single multi-slice CT assessment in patients with
      coronary chronic total occlusion lesions prior to revascularization.
AB  - Accurate assessment of coronary chronic total occlusion (CTO) lesion is essential
      to design an appropriate procedural strategy before revascularization. The
      present study aims to evaluate the significance of a single multislice computed
      tomography (MSCT) examination in patients with CTO lesion. We retrospectively
      analyzed the clinical data of 23 CTO lesions in twenty patients underwent
      computed tomography coronary angiography (CTCA) and SPECT. The CTCA was more
      powerful and sensitive to determine the CTO lesion length (100% v.s 47.8%) and to
      identify the length and location of calcification in occluded vessels compared
      with the coronary angiography (CAG). The LVEF measured by MSCT was comparable to
      that from the gated SPECT. Myocardial perfusion imaging showed that the location
      of the early defect region identified by MSCT was corresponded to the nuclide
      filling defect on the stressed 201thallium-SPECT imaging. The late
      hyperenhancement on MSCT was presented as incomplete nuclide filling on the 99mTc
      MIBI imaging. The results suggested that a single MSCT examination in previous
      myocardial infarction without revascularization facilitates to provide some
      valuable information on the nature of the occluded lesion, myocardial perfusion
      and globe cardiac function, which would be helpful to design appropriate
      revascularization strategy in these subjects. 

PMID- 24905495
TI  - Revisiting liver disease progression in HIV/HCV-coinfected patients: the
      influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3.
AB  - BACKGROUND & AIMS: To perform a comprehensive study on independent modulators of
      liver fibrosis progression and determinants of portal pressure considering immune
      status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels,
      genetic variants of patatin-like phospholipase domain-containing protein 3
      (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of
      HIV/hepatitis C-coinfected (HIV/HCV) patients. PATIENTS & METHODS: 25(OH)D
      deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were
      defined as 25(OH)D <20 ng * ml(-1) , HOMA-IR >2 and CD4nadir <200 cells * MUl(-1)
      respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F
      units divided by the number of years since HCV infection. Patients with a FPR >
      median FPR were assigned to the highFPR group. RESULTS: Among 86 HIV/HCV, the
      median FPR was 0.167 units * years(-1) . While the prevalence of prior alcohol
      abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence
      of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in
      a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are
      not affected by the severity of liver disease. The distribution of IL28B C/C and
      PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR
      patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR:
      5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR
      and showed an additive effect. Portal pressure correlated with prior alcohol
      abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels. CONCLUSIONS: Two
      potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both
      independent modulators of liver fibrosis progression and determinants of portal
      pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR
      in HIV/HCV.

PMID- 24905496
TI  - Increasing levels of cardiolipin differentially influence packing of
      phospholipids found in the mitochondrial inner membrane.
AB  - It is essential to understand the role of cardiolipin (CL) in mitochondrial
      membrane organization given that changes in CL levels contribute to mitochondrial
      dysfunction in type II diabetes, ischemia-reperfusion injury, heart failure,
      breast cancer, and aging. Specifically, there are contradictory data on how CL
      influences the molecular packing of membrane phospholipids. Therefore, we
      determined how increasing levels of heart CL impacted molecular packing in large
      unilamellar vesicles, modeling heterogeneous lipid mixtures found within the
      mitochondrial inner membrane, using merocyanine (MC540) fluorescence. We broadly
      categorized lipid vesicles of equal mass as loosely packed, intermediate, and
      highly packed based on peak MC540 fluorescence intensity. CL had opposite effects
      on loosely versus highly packed vesicles. Exposure of loosely packed vesicles to
      increasing levels of CL dose-dependently increased membrane packing. In contrast,
      increasing amounts of CL in highly packed vesicles decreased the packing in a
      dose-dependent manner. In vesicles that were categorized as intermediate packing,
      CL had either no effect or decreased packing at select doses in a dose
      independent manner. Altogether, the results aid in resolving some of the
      discrepant data by demonstrating that CL displays differential effects on
      membrane packing depending on the composition of the lipid environment. This has
      implications for mitochondrial protein activity in response to changing CL levels
      in microdomains of varying composition. 

PMID- 24905498
TI  - The plant glycosyltransferase clone collection for functional genomics.
AB  - The glycosyltransferases (GTs) are an important and functionally diverse family
      of enzymes involved in glycan and glycoside biosynthesis. Plants have evolved
      large families of GTs which undertake the array of glycosylation reactions that
      occur during plant development and growth. Based on the Carbohydrate-Active
      enZymes (CAZy) database, the genome of the reference plant Arabidopsis thaliana
      codes for over 450 GTs, while the rice genome (Oryza sativa) contains over 600
      members. Collectively, GTs from these reference plants can be classified into
      over 40 distinct GT families. Although these enzymes are involved in many
      important plant specific processes such as cell-wall and secondary metabolite
      biosynthesis, few have been functionally characterized. We have sought to develop
      a plant GTs clone resource that will enable functional genomic approaches to be
      undertaken by the plant research community. In total, 403 (88%) of CAZy defined
      Arabidopsis GTs have been cloned, while 96 (15%) of the GTs coded by rice have
      been cloned. The collection resulted in the update of a number of Arabidopsis GT
      gene models. The clones represent full-length coding sequences without
      termination codons and are Gateway(r) compatible. To demonstrate the utility of
      this JBEI GT Collection, a set of efficient particle bombardment plasmids
      (pBullet) was also constructed with markers for the endomembrane. The utility of
      the pBullet collection was demonstrated by localizing all members of the
      Arabidopsis GT14 family to the Golgi apparatus or the endoplasmic reticulum (ER).
      Updates to these resources are available at the JBEI GT Collection website
      http://www.addgene.org/.

PMID- 24905497
TI  - Value of prominent flow voids without cord edema in the detection of spinal
      arteriovenous fistulae.
AB  - PURPOSE: To determine the prevalence of spinal dural arteriovenous fistulae
      (SDAVF) in patients presenting with prominent vascular flow voids on imaging
      without other imaging findings suggestive of SDAVF. METHODS: We retrospectively
      identified patients from January 1, 2005 to March 1, 2012 who underwent spinal
      angiography for suspected SDAVF with prominent vascular flow voids on prior
      imaging. We excluded patients with other major spinal pathology or other imaging
      findings of SDAVF including cord hyperintensity, enhancement, or expansion. We
      calculated the proportion of patients with positive findings for SDAVF on
      angiography and evaluated the prevalence of SDAVF for this finding alone and in
      correlation with clinical findings. RESULTS: 18 patients underwent spinal
      angiography for prominent flow voids on imaging without other spinal pathology or
      imaging findings of SDAVF. Three had a SDAVF detected on angiography. The
      prevalence of SDAVF in this population was low, only 17% (95% CI 6-39%). All of
      the patients with positive angiography findings had myelopathy, increasing the
      prevalence to 100% if the additional clinical finding of myelopathy was present.
      CONCLUSIONS: Prominent flow voids without other imaging findings suggestive of
      SDAVF is poorly predictive of the presence of a SDAVF, unless myelopathy is
      present clinically.

PMID- 24905499
TI  - Antifungal and cytotoxic 2-acylcyclohexane-1,3-diones from Peperomia alata and P.
      trineura.
AB  - Bioactivity-guided fractionation of the separate CH2Cl2 extracts from the aerial
      parts of Peperomia alata and P. trineura yielded seven polyketides: alatanone A
      [3-hydroxy-2-(5'-phenylpent-4'E-enoyl)cyclohex-2-en-1-one, 1a] and alatanone B [3
      hydroxy-2-(3'-phenyl-6'-methylenedioxypropanoyl)cyclohex-2-en-1-one, 2a] from P.
      alata and trineurone A [3-hydroxy-2-(11'-phenylundec-10'E-enoyl)cyclohex-2-en-1
      one, 1b], trineurone B [3-hydroxy-2-(15'-phenyl-18'
      methylenedioxypentadecanoyl)cyclohex-2-en-1-one, 2b], trineurone C [3-hydroxy-2
      (17'-phenyl-20'-methylenedioxyheptadecanoyl)cyclohex-2-en-1-one, 2c], trineurone
      D [3-hydroxy-2-(hexadec-10'Z-enoyl)cyclohex-2-en-1-one, 3a], and trineurone E
      [(6R)-(+)-3,6-dihydroxy-2-(hexadec-10'Z-enoyl)cyclohex-2-en-1-one, 3b] from P.
      trineura. The isolated compounds were evaluated for antifungal activity against
      Cladosporium cladosporioides and C. sphaeospermum and for cytotoxicity against
      the K562 and Nalm-6 leukemia cell lines. 

PMID- 24905500
TI  - From pair to single: sole fluorophore for ratiometric sensing by dual-emitting
      quantum dots.
AB  - Intrinsic dual-emitting doped ZnS:Mn(2+) quantum dots are promising as sole
      fluorophore for ratiometric sensing. The ratiometric signals are reliably output
      by three kinds of modulation modes, namely, electron transfer, energy transfer,
      and chemical reaction, respectively. Compared with a conventional QD-based pair
      fluorophore system, such a comprehensively ratiometric signal readout from a
      single fluorophore not only means a fundamental breakthrough but will
      substantially simplify the design and greatly promote the application of
      ratiometric sensing. 

PMID- 24905505
TI  - Surgical outcomes for painless drop foot due to degenerative lumbar disorders.
AB  - STUDY DESIGN: Twenty patients presenting with painless drop foot who had
      undergone lumbar spine surgery for degenerative lumbar diseases were included in
      this retrospective study. OBJECTIVE: This study aims to investigate which
      causative factors and patient symptoms significantly affected surgical outcome.
      SUMMARY OF BACKGROUND DATA: Drop foot is a neuromuscular condition that results
      in dorsiflexion palsy of the ankle. Patients with drop foot often complain of leg
      pain. Rarely, patients experience painless drop foot due to lumbar degenerative
      disease. For these patients, the only purpose of surgery is to improve the palsy;
      this makes it difficult to determine whether surgical intervention is indicated.
      No studies have focused on the results of surgical treatment for painless drop
      foot caused by degenerative lumbar diseases. METHODS: Preoperative strength of
      the tibialis anterior and duration of palsy were recorded and considered with
      surgical outcome. RESULTS: Sixty-five percent of patients recovered from drop
      foot after surgery. Drop foot was caused mainly by impairment of the L5 nerve
      root. Patients with a longer duration of palsy had poorer results. CONCLUSIONS:
      Duration of palsy had the greatest effect on recovery. As the only goal of this
      surgery is improvement in the strength of the tibialis anterior, caution must be
      exercised when considering surgery for patients with longstanding palsy.

PMID- 24905507
TI  - Modulation of adenosinergic system and its application for the treatment of
      epilepsy.
AB  - Adenosine is present in all cells and is implicated in the control of the
      function of every tissue and organ. The elevated adenosine levels seem to play a
      significant role in a protection against cellular damage in the regions with
      increased metabolic demand and prevent the subsequent dysfunction of the affected
      organs. Furthermore, adenosine has been shown to play an important role not only
      in the regulation of pathophysiological processes, but also in the modulation of
      normal physiological processes, for example, the regulation of sleep and arousal
      as well as by impact on pre- or postsynaptic receptors involved in releasing
      neurotransmitters (e.g. glutamate, acetylcholine, norepinephrine, 5
      hydroxytryptamine, dopamine, GABA and others). Experimental studies provide
      evidence supporting the role of adenosine as an endogenous anticonvulsant agent.
      Numerous adenosine agonists acting through A1, A2 and A3 receptors were proven as
      potent anticonvulsant compounds in a wide variety of animal models of epilepsy.
      However, despite their efficacy in such models, adenosine receptor agonists do
      not appear to be good candidates for successful clinical applications. The
      therapeutic range of systemically administered adenosine receptor agonists is
      very narrow and they often produce profound adverse events. It seems, therefore,
      that adenosine receptor agonists could only be used clinically when co
      administered with other antiepileptic drugs or when used in local therapies,
      where their side effect profile is much more tolerable. An alternative strategy
      would be to enhance the natural adenosinergic feedback mechanism triggered by
      seizures by using adenosine uptake inhibitors. This approach seems very
      attractive as it would allow limiting the action only in the active areas such as
      seizure foci and thus, preventing the systemic side effects. 

PMID- 24905508
TI  - Glutamate and modeling of schizophrenia symptoms: review of our findings: 1990
      2014.
AB  - In the early 90s, we studied the role of perception disturbances in schizophrenia
      in our first clinical approaches, using the Bender test in schizophrenic
      patients. Results were clear, showing a shape discrimination failure. Following
      this initial results, we reproduced nuclear symptoms of schizophrenia in animal
      models, showing that perceptual disturbances, acquisition disturbances, decrease
      in affective levels and working memory disturbances can be induced by specific N
      methyl-D-aspartic acid (NMDA) glutamatergic blockade within the nucleus accumbens
      septi (NAS). We studied also another glutamatergic and dopaminergic drugs,
      finding that a decrease in glutamatergic transmission within NAS led to cognitive
      disturbances and affective flattening. An increase in glutamatergic transmission
      fully enhances cognition in the tasks used. Dopaminergic D-2 antagonists
      partially improved cognition. Our results link the proposed corticostriatal
      dysfunction with the thalamocortical disturbances underlying perceptual problems,
      but also influencing affective levels and cognitive variables. According to our
      translational findings, core schizophrenia symptoms may be translationally
      reproduced antagonizing NMDA receptors within NAS, and improved blocking the
      glutamate auto-receptor. Dopaminergic transmission appears to have a role in
      therapeutic but not in the early pathophysiology of schizophrenia.

PMID- 24905509
TI  - Pharmacological characterization of carrageenan induced heat muscle hyperalgesia
      in rats using non-selective, preferential and selective COX-2 inhibitors.
AB  - BACKGROUND: Previous studies have shown that unilateral injection of carrageenan
      into the gastrocnemius muscle produces chronic thermal and mechanical
      hyperalgesia. AIM: In the present study, we have characterized this model of
      muscoskeletal inflammatory pain, by evaluating the antihyperalgesic effects of
      selective and non-selective COX-2 inhibitors after systemic administration.
      MATERIALS AND METHODS: Rats were injected with 3% carrageenan in the left
      gastrocnemius muscle and hyperalgesia to heat stimuli (measured as decreased
      withdrawal latency) to paws was assessed before and at varying times after
      injection, till end of 2nd week. Histological changes and the determination of
      prostaglandin E2 (PGE2) concentration were performed after the completion of drug
      treatment protocol. RESULTS: Intraperitoneal administrations of the selective COX
      2 inhibitor celecoxib (7 mg/kg) as well as preferential COX-2 inhibitors like
      nimisulide (5mg/kg) and aceclofenac (5mg/kg) attenuated hyperalgesia whereas non
      COX-2 selective inhibitors like ibuprofen (40 mg/kg) and indomethacin (10mg/kg)
      did not. Also the histopathological evidence suggests the beneficial effects of
      COX-2 selective inhibitors. The data suggest that selective inhibition of COX-2
      produce good anti-inflammatory, analgesic and antihyperalgesic effects on
      Carrageenan-induced thermal inflammatory hyperalgesia. CONCLUSION: In the present
      carrageenan induced chronic pain model we have determined the role of analgesics
      in the reversal and inhibition of the state of chronic hyperalgesia. While
      considering the characterization of the present model our observations suggest
      the importance of a spinal COX-2 mechanism, a spinal action of systemically
      delivered drugs in the face of peripheral inflammation.

PMID- 24905510
TI  - Mechanisms of the sarcoplasmic reticulum Ca2+ release induced by P2X receptor
      activation in mesenteric artery myocytes.
AB  - BACKGROUND: ATP is one of the principal sympathetic neurotransmitters which
      contracts vascular smooth muscle cells (SMCs) via activation of ionotropic P2X
      receptors (P2XRs). We have recently demonstrated that contraction of the guinea
      pig small mesenteric arteries evoked by stimulation of P2XRs is sensitive to
      inhibitors of IP3 receptors (IP3Rs). Here we analyzed contribution of IP3Rs and
      ryanodine receptors (RyRs) to [Ca(2+)]i transients induced by P2XR agonist
      alphabeta-meATP (10 MUM) in single SMCs from these vessels. METHODS: The effects
      of inhibition of L-type Ca(2+) channels (VGCCs), RyRs and IP3Rs (5 MUM
      nicardipine, 100 MUM tetracaine and 30 MUM 2-APB, respectively) on alphabeta
      meATP-induced [Ca(2+)]i transients were analyzed using fast x-y confocal Ca(2+)
      imaging. RESULTS: The effect of IP3R inhibition on the [Ca(2+)]i transient was
      significantly stronger (67 +/- 7%) than that of RyR inhibition (40 +/- 5%) and
      was attenuated by block of VGCCs. The latter indicates that activation of VGCCs
      is linked to IP3R-mediated Ca(2+) release. Immunostaining of RyRs and IP3Rs
      revealed that RyRs are located mainly in deeper sarcoplasmic reticulum (SR) while
      sub-plasma membrane (PM) SR elements are enriched with type 1 IP3Rs. This
      structural peculiarity makes IP3Rs more accessible to Ca(2+) entering the cell
      via VGCCs. Thus, IP3Rs may serve as an "intermediate amplifier" between voltage
      gated Ca(2+) entry and RyR-mediated Ca(2+) release. CONCLUSIONS: P2X receptor
      activation in mesenteric artery SMCs recruits IP3Rs-mediated Ca(2+) release from
      sub-PM SR, which is facilitated by activation of VGCCs. Sensitivity of IP3R
      mediated release to VGCC antagonists in vascular SMCs makes this mechanism of
      special therapeutic significance.

PMID- 24905511
TI  - Comparison of the effects of methanethiol and sodium sulphide on uterine
      contractile activity.
AB  - BACKGROUND: Our aim was to investigate the effect of methanethiol (CH3SH) on
      contractility of rat uterus and activities of redox-active enzymes, and to
      compare them with the effect of sodium sulphide (Na2S), a hydrogen sulphide
      (H2S/HS(-)) donor. METHODS: Uteri were isolated from virgin Wistar rats, divided
      into six groups, controls (untreated uteri allowed to contract spontaneously and
      in the presence of Ca(2+)(6mM)), CH3SH treated (spontaneously active and Ca(2+)
      induced) and Na2S treated (spontaneously active and Ca(2+) induced). Underlying
      antioxidative enzyme activities (superoxide dismutase--SOD, glutathione
      peroxidase--GSHPx, glutathione reductase--GR) in CH3SH- or Na2S-treated uteri
      were compared to controls. RESULTS: Our experiments showed that CH3SH and Na2S
      provoked reversible relaxation of both spontaneous and Ca(2+)-induced uterine
      contractions. The dose-response curves differed in shape, and CH3SH curve was
      shifted to higher concentration compared to H2S/HS(-). The effects of Na2S fitted
      sigmoid curve, whereas those of CH3SH fitted linearly. CH3SH provoked increased
      SOD activity and decreased GR activity. However, Na2S (H2S/HS(-)) provoked an
      increase in SOD activity exclusively in Ca(2+)-stimulated uteri, while the
      activity of GSHPx was increased in both types of active uteri. CONCLUSION: Our
      results imply that CH3SH may have a constructive role in the control of muscle
      function and metabolism. Observed differences between CH3SH and H2S/HS(-) could
      be attributed to a larger moiety that is present in CH3SH compared to H2S, but
      they are more likely to be a consequence of the specific actions of HS(-), in
      relation to its negative charge.

PMID- 24905512
TI  - Tumor necrosis factor alpha abolished the suppressive effect of insulin on
      hepatic glucose production and glycogenolysis stimulated by cAMP.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNFalpha) is implicated in the
      development of insulin resistance in obesity, type 2 diabetes and cancer.
      However, its ability to modulate the action of insulin on glycogen catabolism in
      the liver is controversial. The aim of the present study was to investigate
      whether TNFalpha acutely affects the suppression by insulin of hepatic glucose
      production (HGP) and glycogenolysis stimulated by cyclic adenosine monophosphate
      (cAMP). METHODS: TNFalpha (10 MUg/kg) was injected intravenously to rats and, 1
      or 6h later, their livers were subjected to in situ perfusion with cAMP (3 MUM),
      in the presence or absence of physiological (20 MUU/mL) or supraphysiological
      (500 MUU/mL) concentrations of insulin. RESULTS: The injection of TNFalpha, 1 or
      6h before liver perfusion, had no direct effect on the action of cAMP in
      stimulating HGP and glycogenolysis. However, when TNFalpha was injected 1h, but
      not 6h, before liver perfusion it completely abolished (p<0.05) the suppressive
      effect of 20 MUU/mL insulin on HGP and glycogenolysis stimulated by cAMP.
      Furthermore, the injection of TNFalpha 1h or 6h before liver perfusion did not
      influence the suppression of cAMP-stimulated HGP and glycogenolysis by 500 MUU/mL
      insulin. CONCLUSION: TNFalpha acutely abolished the suppressive effect of
      physiological, but not supraphysiological, levels of insulin on HGP and
      glycogenolysis stimulated by cAMP, suggesting an important role of this mechanism
      to the increased HGP in several pathological states.

PMID- 24905513
TI  - Opioid modulation of prolactin secretion induced by stress during late pregnancy.
      Role of ovarian steroids.
AB  - BACKGROUND: The opioid system modulates prolactin release during late pregnancy.
      Its role and the participation of ovarian hormones in this modulation are
      explored in ether stress-induced prolactin release. METHODS/RESULTS: Estrous, 3
      day and 19-day pregnant rats were used. We administered the antagonist
      mifepristone (Mp) and tamoxifen to evaluate progesterone and estradiol action in
      naloxone (NAL, opioid antagonist) or saline treated rats. Ether stress had no
      effect on serum prolactin levels in controls but increased prolactin release in
      NAL-treated rats. Prolactin response to stress in NAL-treated rats was blocked by
      l-DOPA administration. Mp treatment on day 18 of pregnancy increased prolactin
      levels after stress without alterations by NAL. Tamoxifen on days 14 and 15 of
      pregnancy completely blocked Mp and NAL effects on prolactin release at late
      pregnancy. In contrast, stress significantly increased prolactin levels in
      estrous rats and pretreatment with NAL prevented this. On day 3 of pregnancy, at
      6.00 p.m., stress and NAL treatment inhibited prolactin levels in saline-treated
      rat. No effect of stress or NAL administration was detected on day 3 of pregnancy
      at 9.00 a.m. icv administration of specific opioids antagonist, B-Funaltrexamine
      but not Nor-Binaltorphimine or Naltrindole, caused a significant increase in
      stress-induced prolactin release. CONCLUSIONS: Opioid system suppression of
      prolactin stress response during late pregnancy was observed only after
      progesterone withdrawal, involving a different opioid mechanism from its well
      established stimulatory role. This mechanism acts through a mu opioid receptor
      and requires estrogen participation. The opioid system and progesterone may
      modulate stress-induced prolactin release, probably involving a putative
      prolactin-releasing factor.

PMID- 24905514
TI  - Role of glutamate and advantages of combining memantine with a 5HT6 ligand in a
      model of depression.
AB  - BACKGROUND: It is a well-known fact that 5HT6 ligands increase glutamate levels.
      In the current study we investigated whether a 5HT6 antagonist, SB399885 would
      show antidepressant like property at a dose which would significantly increase
      the glutamate levels. Further we studied if the combination of a 5HT6 antagonist
      and N-methyl-D-aspartate (NMDA) antagonist, memantine would restore the
      antidepressant property. As dementia and depression are co-morbid, we evaluated
      if this combination would have an effect on cognition. METHODS: The
      antidepressant like property of SB399885 alone and in combination with memantine
      was investigated using the forced swim test (FST). Object recognition task (ORT)
      was used to investigate the combination therapy on cognition. Additionally,
      glutamate levels in prefrontal cortex and corresponding brain concentration of
      SB399885 were determined. RESULTS: Brain concentrations of SB399885 equal to or
      greater than 553 nM significantly increased brain glutamate levels and reduced
      immobility time in FST. When combined with memantine, glutamate levels and
      immobility time in FST was reduced. A dose dependent increase in the
      discriminative index was observed in ORT. CONCLUSION: Loss of antidepressant like
      property seen at the highest tested dose of SB399885 could be due to increased
      glutamate levels which was reversed by memantine. Combining memantine and
      SB399885 offers the advantage of extending the therapeutic window of
      antidepressant like property of SB399885 as well as having procognitive effect.
      The combination therapy holds promise in treatment of dementia associated with
      depression.

PMID- 24905515
TI  - Orphenadrine-induced convulsive status epilepticus in rats responds to the NMDA
      antagonist dizocilpine.
AB  - BACKGROUND: Identification of new molecular targets as well as the new models
      recapitulating different aspects of pathophysiology of status epilepticus (SE) in
      humans might prove essential for the breakthrough in the efforts against
      pharmacoresistance in epilepsy. Recently, we described a new model of generalized
      convulsive SE induced with orphenadrine (ORPH) in rats with unique
      characteristics [5]. The current study was aimed at assessing the efficacy of a
      new generation antiepileptic drugs (AEDs) and some of the experimental agents in
      suppressing ORPH-evoked seizures in rats. METHODS: ORPH was administered
      intraperitoneally (ip) in the dose of 80 mg/kg in male Wistar rats. The latency
      to first seizure, the number of seizure episodes and the duration of overt SE, as
      well as the incidence of deaths was scored with simultaneous
      electroencephalographic (EEG) recordings. RESULTS: ORPH induced seizures in 100%
      of animals at a dose of 80 mg/kg, associated with low mortality and good
      behavioural outcome. Among new generation AEDs: felbamate, levetiracetam,
      topiramate, lamotrigine and progabide did not affect the seizure incidence. Among
      the experimental drugs, only dizocilpine, the non-competitive NMDA antagonist,
      dose-dependently affected the occurrence of the SE (p<0.001). However, CGP-39551
      competitive NMDA antagonist, the same as scopolamine and mecamylamine (muscarinic
      and nicotinic receptors antagonists, respectively) showed no effect. CONCLUSIONS:
      Based on the above findings, one may speculate that NMDA activation is partly
      involved in the proconvulsant activity of orphenadrine but may not be the primary
      pathomechanism. ORPH-induced seizures may provide an interesting option for
      studying novel targets for pharmacological interventions in status epilepticus.

PMID- 24905516
TI  - The influence of aripiprazole, olanzapine and enriched environment on depressant
      like behavior, spatial memory dysfunction and hippocampal level of BDNF in
      prenatally stressed rats.
AB  - BACKGROUND: Cognitive function deficits caused by impaired neurogenesis of the
      brain structures are considered an important pathogenic factor in many
      neurological and mental diseases such as schizophrenia and depression. The aim of
      the study was to determine the effect of the enriched environment on cognitive
      functions and antidepressant-like effect of prenatally stressed rats. It was
      important to determine the effect of aripiprazole ARI and olanzapine OLA and
      clarify whether the enriched environment induces increases in brain derived
      neurothropic factor BDNF in the hippocampus in the prenatally stressed group
      (PSG) and non-stressed control group (NSCG). METHODS: The effect of chronic
      stress applied to pregnant rats and the use of ARI (1.5mg/kg ip) and OLA
      (0.5mg/kg ip) were studied in the Morris water maze (MWM), Porsolt Forced
      swimming test (FST) and by determining BDNF levels. RESULTS: The results
      indicated that enriched environment improved spatial memory and also had an
      antidepressant-like effect on prenatally stressed rats. ARI improved spatial
      memory both in the NSCG and PSG, while OLA caused memory improvement only in the
      PSG. Moreover, both ARI and OLA reduced immobility time in the NSCG and PSG. In
      PSG rats, BDNF decrease was observed while chronic treatment with ARI and OLA
      increased BDNF levels in the hippocampi of NSCG and PSG rats. CONCLUSION: It has
      been confirmed that enriched environment improves spatial memory of animals,
      removes symptoms of stress, has an antidepressant-like effect, and that new
      neuroleptics, such as ARI or OLA, modulate these functions (increased BDNF).

PMID- 24905517
TI  - Effect of glimepiride on the skeletal system of ovariectomized and non
      ovariectomized rats.
AB  - BACKGROUND: Diabetes mellitus type 2 and osteoporosis are major health problem,
      especially in postmenopausal women. Glimepiride is a third-generation
      sulfonylurea derivative and is used as a first-line drug in the treatment of type
      2 diabetes mellitus. The effect of this drug on bone tissue is unknown. The aim
      of the present study was to investigate the influence of glimepiride on the
      skeletal system in ovariectomized and non-ovariectomized rats. METHODS: The
      experiment was conducted on 3-month-old female Wistar rats, divided into 4 groups
      (n=10 per group): I (NOVX)-non-ovariectomized control rats, II (NOVX+G)-non
      ovariectomized rats receiving glimepiride (0.8 mg/kg po), III (OVX)
      ovariectomized control rats, IV (OVX+G)-ovariectomized rats receiving glimepiride
      (0.8 mg/kg po). Bilateral ovariectomy was performed 7 days before the start of
      the experiment, under ketamine-xylazine anesthesia. Glimepiride was administered
      once daily for 28 days. The effect of glimepiride on the skeletal system was
      assessed based on macrometric parameters, histomorphometric parameters and
      mechanical properties of the tibial metaphysis, femoral diaphysis and femoral
      neck. Bone mass, mineral mass, calcium and phosphorus content, as well as serum
      estrogen, osteocalcin and RatLaps levels were also studied. RESULTS: Estrogen
      deficiency in ovariectomized rats caused increased bone remodeling, with an
      intensification of bone resorption and formation, and mineralization impairment.
      Glimepiride in ovariectomized rats inhibited the development of changes in the
      skeletal system caused by estrogen deficiency, intensifying bone formation. In
      the presence of estrogens (in non-ovariectomized rats), glimepiride also
      intensified bone formation, but to a lesser extent. CONCLUSIONS: Glimepiride, in
      the therapy of type 2 diabetes mellitus in postmenopausal women, may have a
      beneficial effect on bone remodeling and may reduce the risk of development of
      osteoporosis.

PMID- 24905518
TI  - Metformin affects macrophages' phenotype and improves the activity of glutathione
      peroxidase, superoxide dismutase, catalase and decreases malondialdehyde
      concentration in a partially AMPK-independent manner in LPS-stimulated human
      monocytes/macrophages.
AB  - BACKGROUND: Diabetic patients experience accelerated atherosclerosis. Metformin
      is a cornerstone of the current therapy of type 2 diabetes. Macrophages are the
      key cells associated with the development of atherosclerotic plaques. Therefore,
      our aim was to assess the in vitro effects of metformin on macrophages and its
      influence on the mechanisms involved in the development of atherosclerosis.
      MATERIALS AND METHODS: Peripheral blood mononuclear cells were obtained from the
      group including 16 age-matched healthy non-smoking volunteers aged 18-40 years.
      Monocytes were further incubated with metformin, LPS and compound C--a
      pharmacological inhibitor of AMPK. The impact of metformin on oxidative stress
      markers, antioxidative properties, inflammatory cytokines and phenotypical
      markers of macrophages was studied. RESULTS: We showed that macrophages treated
      with metformin expressed less reactive oxygen species (ROS), which resulted from
      increased antioxidative potential. Furthermore, a reduction in inflammatory
      cytokines was observed. We also observed a phenotypic shift toward the
      alternative activation of macrophages that was induced by metformin. All the
      aforementioned results resulted from AMPK activation, but a residual activity of
      metformin after AMPK blockade was still noticeable even after inhibition of AMPK
      by compound C. CONCLUSIONS: Authors believe that metformin-based therapy, a
      cornerstone in diabetes therapy, not only improves the prognosis of diabetics by
      reducing blood glucose but also by reducing oxidative stress, inflammatory
      cytokine production and the shift toward alternative activation of macrophages.

PMID- 24905519
TI  - Reboxetine and its influence on the action of classical antiepileptic drugs in
      the mouse maximal electroshock model.
AB  - BACKGROUND: Our previous studies revealed that different classes of
      antidepressant drugs differently affect seizure phenomena. Continuing our
      research in this field, in the present study we wanted to investigate the
      influence of acute and chronic treatment with reboxetine, a selective
      norepinephrine reuptake inhibitor, on the anticonvulsant action of classical
      antiepileptic drugs. METHODS: Experiments were conducted in the model of
      electroconvulsive threshold and maximal electroshock in mice. Motor coordination
      was evaluated in the chimney test and long term memory in the step-through
      passive avoidance task. Brain concentrations of antiepileptic drugs were detected
      by fluorescence polarization immunoassay. RESULTS: Acute treatment with
      reboxetine (8-16 mg/kg) significantly raised the electroconvulsive threshold. In
      contrast, chronic reboxetine (2-16 mg/kg) did not affect this parameter. Single
      administration of the antidepressant applied at its subthreshold doses enhanced
      the action of valproate, carbamazepine and phenobarbital. The antielectroshock
      effect of phenytoin was also potentiated by acute reboxetine, but only at doses
      increasing the threshold. Repeated administration of reboxetine (8-12 mg/kg)
      enhanced the anticonvulsant action of carbamazepine, but not that of three
      remaining antiepileptic drugs. Neither acute nor chronic reboxetine changed the
      brain concentrations of valproate, carbamazepine, phenytoin or phenobarbital.
      Therefore, all revealed interactions seem to be pharmacodynamic. In terms of
      undesired effects, acute/chronic reboxetine and its combinations with classical
      antiepileptic drugs did not significantly impair motor performance or long-term
      memory in mice. CONCLUSIONS: As far as the obtained data can be extrapolated into
      clinical conditions, it seems that reboxetine may be safely used in the treatment
      of depressive disorders in epileptic patients.

PMID- 24905520
TI  - Telmisartan attenuates cognitive impairment caused by chronic stress in rats.
AB  - BACKGROUND: The potential effect of chronic treatment with telmisartan, an
      angiotensin type 1 receptor blocker (ARB) and partial agonist of peroxisome
      proliferator--activated receptor gamma (PPARgamma), on stress-related disorders
      is a matter of considerable interest. The existing data suggest that angiotensin
      II (Ang II) plays a major role in exaggerated sympathetic and hormonal response
      to stress. Enhanced formation of Ang II and increased AT1 receptor activity is
      associated with devastating impact of stress on central nervous system, which may
      trigger many psychiatric disorders such as depression, schizophrenia or post
      traumatic stress disorder. Some of the anti-stress effects of ARBs have already
      been proven but these on the stress-induced cognitive impairment were examined
      only for candesartan. In this study, we tested a hypothesis that blockade of
      stress response by another ARB telmisartan alleviates the negative effect of
      prolonged restraint stress on cognitive functions of male Wistar rats. METHODS:
      The preventive action of long-lasting treatment with telmisartan (1mg/kg body
      weight) against impairment caused by chronic stress (2h daily for 21 days) on
      recall was evaluated in a passive avoidance (PA) situation and object recognition
      test (ORT). Locomotor activity and anxiety behavior were tested respectively, in
      an open field and an elevated plus-maze. RESULTS: The results of this study
      indicate that telmisartan diminishes deleterious effects of chronic restraint
      stress on memory in a statistically significant manner (p<0.01) in both, PA
      situation and ORT. CONCLUSION: It appears that telmisartan may constitute a new
      therapeutic option in a stress-related cognitive impairment.

PMID- 24905521
TI  - The effect of ezetimibe on adipose tissue hormones in patients with isolated
      hypercholesterolemia.
AB  - BACKGROUND: Extra-lipid effects of ezetimibe, a new lipid-lowering agent, are so
      far poorly understood. METHODS: Twenty-two patients with elevated total and LDL
      cholesterol levels, statin-intolerant or having contraindications to statin
      therapy, were treated with ezetimibe (10mg daily) for 90 days. Plasma levels of
      lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin,
      visfatin, tumor necrosis factor-alpha (TNF-alpha), free fatty acids (FFA) and
      high sensitivity C-reactive protein (hsCRP) were examined at the beginning of the
      study and after 30 and 90 days of treatment. RESULTS: Compared with the control
      age-, sex-, and weight-matched healthy subjects, isolated hypercholesterolemic
      patients exhibited higher plasma levels of leptin, visfatin and TNF-alpha and
      lower plasma levels of adiponectin. Their baseline FFA and hsCRP levels were also
      increased. Ezetimibe decreased circulating levels of total cholesterol, LDL
      cholesterol and apolipoprotein B-100. The drug significantly reduced plasma
      levels of visfatin and only tended to reduce plasma levels of leptin, TNF-alpha,
      visfatin, FFA and CRP. The effect of ezetimibe on these markers was lipid
      independent but stronger in insulin-sensitive than in insulin-resistant patients.
      CONCLUSIONS: The obtained results indicate that the presence of isolated
      hypercholesterolemia is associated with abnormal hormonal function of the adipose
      tissue. They also show that ezetimibe induces relatively small changes in adipose
      tissue hormonal function and systemic inflammation in patients with elevated
      cholesterol levels.

PMID- 24905522
TI  - Mortality in hypertensive patients with coronary heart disease depends on
      chronopharmacotherapy and dipping status.
AB  - BACKGROUND: The goal of our study was to assess the influence of hypertension
      chronopharmacotherapy on diurnal blood pressure (BP) profile and mortality.
      METHODS: Subjects with established coronary heart disease (CHD) (n = 1345, mean
      age 63.2 +/- 9.2 years) were included. RESULTS: Non-dipping status was related to
      a lack of nighttime hypertensive drug administration (OR 3.87, 95% CI 3.00-4.98).
      In a Cox proportional hazards regression model, non-dipping status (HR 1.17, 95%
      CI 1.02-1.47) and non-nighttime antihypertensive drug administration (HR 1.13,
      95% CI 1.01-1.45) were predictors of all-cause mortality. CONCLUSIONS: The non
      dipping profile of CHD patients and increased mortality were related to a lack of
      antihypertensive drug administration at bedtime.

PMID- 24905523
TI  - Essential difference between the pharmacological spectrum of (-)-deprenyl and
      rasagiline.
AB  - BACKGROUND: (-)-Deprenyl and rasagiline are classified as selective inhibitors of
      B-type MAO. The DATATOP study revealed that the administration of (-)-deprenyl to
      untreated patients with Parkinson's disease (PD) significantly delays the need
      for levodopa therapy (Parkinson Study Group, 1989). Rasagiline was ineffective in
      this respect (Parkinson Study Group, 2002). The aim of this paper is to explain
      the reasoning behind the differentiation between (-)-deprenyl and rasagiline.
      METHODS: In the shuttle box the acquisition of a two way conditioned avoidance
      response (CAR) was analyzed on male Wistar rats during 5 consecutive days.
      Tetrabenazine-treatment (1mg/kg sc) depletes the transmitters from their stores
      in the nerve terminals of the catecholaminergic neurons and blocks the
      acquisition of a CAR. Catecholaminergic activity enhancer (CAE) substances [(-)
      deprenyl, (-)-BPAP] fully antagonize the tetrabenazine-induced learning deficit.
      Using (-)-deprenyl and (-)-BPAP as reference substances, we measured the effect
      of rasagiline and J-508 in this test. Rasagiline is the desmethyl-analog of J
      508, described by Knoll in 1978. RESULTS: In contrast to (-)-deprenyl and (-)
      BPAP, J-508 and rasagiline were found in the shuttle box test to be devoid of the
      CAE effect. CONCLUSIONS: Since convincing experimental and clinical evidence
      speaks in favor for the conclusion that the catecholaminergic activity enhancer
      (CAE) effect of (-)-deprenyl is responsible for the significantly delayed need
      for levodopa therapy in untreated patients with PD (Knoll, 2012) and rasagiline
      is devoid of the CAE effect, this might explain why "...based on current
      evidence, rasagiline cannot be said to definitely have a disease-modifying
      effect" [Robottom, 2011].

PMID- 24905524
TI  - Analgesic effects of antidepressants alone and after their local co
      administration with morphine in a rat model of neuropathic pain.
AB  - BACKGROUND: The therapy of neuropathic pain may include the use of co-analgesics,
      such as antidepressants, however, their desired analgesic effect is associated
      with significant side effects. An alternative approach to this is their local
      administration which has been proposed, but there is little data regarding their
      local co-administration with morphine and the nature of the interaction between
      morphine and either doxepin or venlafaxine, two antidepressant drugs that have
      been recently used in neuropathic pain therapies. METHODS: This study was
      performed on rats after chronic constriction injury (CCI) to the sciatic nerve.
      The von Frey and Hargreaves' tests were used to assess mechanical allodynia and
      thermal hyperalgesia, respectively, after intraplantar (ipl) or subcutaneous (sc)
      administration of amitriptyline, doxepin, or venlafaxine, or their ipl co
      administration with morphine on day 12-16 after injury. RESULTS: The ipl
      administration of amitriptyline (3, 15 mg), doxepin (1, 5, 10, 15 mg), or
      venlafaxine (2, 7 mg) was effective in antagonizing CCI-induced allodynia. Their
      sc injection at a site distal to the injured side, did not induce alterations in
      pain thresholds, which supports the local mode of action. Of the three
      antidepressants used in this study, only ipl co-administration of amitriptyline
      with morphine significantly enhanced its effect in contrast to doxepin and
      venlafaxine, both of which weakened the analgesic effect of morphine.
      CONCLUSIONS: In summary, the results suggest that when amitriptyline (but not
      doxepin or venlafaxine) is locally co-administered with morphine the
      effectiveness under neuropathic pain is enhanced, although additional studies are
      necessary to explain differential mechanisms of interaction of antidepressant
      drugs with morphine after local administration.

PMID- 24905525
TI  - Modulation by kynurenine of extracellular kynurenate and glutamate in cerebral
      cortex of rats with acute liver failure.
AB  - BACKGROUND: Kynurenic acid (KYNA) modulates the glutamatergic tone by controlling
      neuronal glutamate (GLU) release. The present study tested the potential of the
      KYNA precursor, kynurenine (KYN) to counter increased extracellular GLU
      associated with the pathogenesis of hepatic encephalopathy accompanying acute
      liver failure (ALF). METHODS: ALF was induced in adult rats by administration of
      a hepatotoxin, thioacetamide. KYNA and GLU were measured in the cerebral cortical
      microdialysates of control (saline-treated) and ALF rats using HPLC. The
      expression of mRNA coding for kynurenine aminotransferase II (KAT-II), the
      astrocytic enzyme converting KYN to KYNA, was assayed by real-time PCR. RESULTS:
      Cerebral cortical extracellular KYNA was increased in ALF rats not treated with
      KYN, consistent with a previously observed increase of cerebral cortical KATII
      activity in this ALF model. Single intraperitoneal administration of KYN (50
      mg/kg, 120 min before microdialysate collection), produced a further substantial
      increase of extracellular KYNA, paralleled by a decrease of extracellular GLU. In
      cultured cerebral cortical astrocytes, the cells which in situ are the primary
      target of blood-derived ammonia and other toxins liberated due to ALF, elevation
      of KAT-II mRNA expression was noted upon their incubation with KYN and the KYN
      precursor, tryptophan (Trp), which is normally elevated by ALF. CONCLUSIONS:
      Administration of exogenous KYN to stimulate KYNA synthesis may help correcting
      excessive extracellular accumulation of GLU in cerebral cortex caused by ALF. The
      therapeutic potential of KYN in ALF appears to be fostered by increased
      expression of KAT-II in astrocytes upon exposure to KYN or Trp.

PMID- 24905526
TI  - A novel synthetic HTB derivative, BECT inhibits lipopolysaccharide-mediated
      inflammatory response by suppressing the p38 MAPK/JNK and NF-kappaB activation
      pathways.
AB  - Activated microglia cells are well recognized as mediators of neuroinflammation,
      as they release nitric oxide and pro-inflammatory cytokines in various
      neuroinflammatory diseases. Thus, suppressing microglial activation may alleviate
      neuroinflammatory and neurodegenerative processes. In the present study, we
      synthesized and investigated the anti-neuroinflammatory effect of a novel HTB (2
      hydroxy-4-trifuoromethylbenzoic acid) derivative in lipopolysaccharide (LPS)
      stimulated microglial cells. Among the synthesized derivatives, the BECT [But-2
      enedioic acid bis-(2-carboxy-5-trifluoromethyl-phenyl) ester] significantly
      decreased production of nitric oxide and other pro-inflammatory cytokines
      including tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in
      microglial cells. BECT also mitigated the expression of inducible nitric oxide
      synthase and cyclooxygenase-2 at both the mRNA and protein levels. Further
      mechanistic studies demonstrated that the HTB derivative inhibited
      phosphorylation of JNK and p38 mitogen-activated protein kinase and nuclear
      translocation of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells.
      Thus BECT, our novel synthesized compound have anti-inflammatory activity in
      microglial cells, and may have therapeutic potential for treating
      neuroinflammatory diseases. 

PMID- 24905527
TI  - Berberine inhibits LPS-induced TF procoagulant activity and expression through NF
      kappaB/p65, Akt and MAPK pathway in THP-1 cells.
AB  - BACKGROUND: Considering the key role of TF in coagulation of sepsis or acute lung
      injury (ALI), we investigated whether berberine (BBR) could inhibit TF expression
      and procoagulant activity and explored its possible mechanism. METHODS: The
      effects of berberine on the expression, procoagulant activity of TF and related
      signal pathways induced by lipopolysaccharide (LPS) were observed in THP-1 cells.
      RESULTS: Our results showed that berberine could inhibit LPS-induced TF activity
      and expression, and down-regulate NF-kappaB, Akt and MAPK/JNK/p38/ERK pathways.
      CONCLUSION: Berberine inhibits TF expression and related pathway, which provides
      some new insights on its mechanism for sepsis treatment.

PMID- 24905528
TI  - Interaction of famotidine, an H2 histamine receptor antagonist, with conventional
      antiepileptic drugs in mice.
AB  - H2 histamine receptors are localized postsynaptically in the CNS. The aim of this
      study was to evaluate the effects of acute (1 day) and prolonged (7 day)
      administration of the H2 histamine receptor antagonist, famotidine, on the
      anticonvulsant activity of conventional antiepileptic drugs (AEDs; valproate,
      carbamazepine, diphenylhydantoin and phenobarbital) against maximal electroshock
      (MES)-induced seizures in mice. In addition, the effects of these drugs alone or
      in combination with famotidine were studied on motor performance and long-term
      memory. The influence of H2 receptor antagonist on brain concentrations and free
      plasma levels of the antiepileptic drugs was also evaluated. After acute or
      prolonged administration of famotidine (at dose of 10mg/kg) the drug raised the
      threshold for electroconvulsions. No effect was observed on this parameter at
      lower doses. Famotidine (5mg/kg), given acutely, significantly enhanced the
      anticonvulsant activity of valproate, which was expressed by a decrease in ED50.
      After the 7-day treatment, famotidine (5mg/kg) increased the anticonvulsant
      activity of diphenylhydantoin against MES. Famotidine (5mg/kg), after acute and
      prolonged administration, combined with valproate, phenobarbital,
      diphenylhydantoin and carbamazepine did not alter their free plasma levels. In
      contrast, brain concentrations of valproate were elevated for 1-day treatment
      with famotidine (5mg/kg). Moreover, famotidine co-applied with AEDs, given
      prolonged, worsened motor coordination in mice treated with carbamazepine or
      diphenylhydantoin. In contrast this histamine antagonist, did not impair the
      performance of mice evaluated in the long-term memory task. The results of this
      study indicate that famotidine modifies the anticonvulsant activity of some
      antiepileptic drugs. 

PMID- 24905529
TI  - Circadian profile of salivary melatonin secretion and its concentration after
      epileptic seizure in patients with drug-resistant epilepsy--preliminary report.
AB  - BACKGROUND: The results of a few previous studies assessing melatonin
      concentration in epileptic patient are ambiguous. This study aimed at: (1)
      comparing the circadian profile of salivary melatonin excretion in epileptic
      patients with that in healthy subjects and with circadian frequency profile of
      seizures and (2) assessing the effect of epileptic seizure upon salivary
      melatonin concentration. METHODS: The study included thirty patients suffering
      from drug-resistant epilepsy aged from 22 to 45 years (mean age 37.17, SD +/-
      10.25). All subjects had their saliva taken in order to determine melatonin
      concentration and its circadian excretion profile performed every 4h.
      Additionally, saliva samples were collected in order to assess concentration of
      melatonin directly after epileptic seizure and 2h later. RESULTS: The circadian
      profile of melatonin secretion in epileptic patients did not differ significantly
      from a profile in healthy subjects. Epileptic women showed statistically higher
      average salivary melatonin concentration at 2a.m., 6a.m. and 10a.m., compared to
      epileptic men; this may be related to lower age average of women as well as to
      their different hormonal profile. CONCLUSION: The significantly higher salivary
      melatonin concentration at 6a.m. in patients with diurnal seizures (occurring
      mainly in the morning) may suggest proconvulsive effect of this hormone.
      Epileptic seizure did not lead to significantly elevated salivary melatonin
      concentration. Epileptogenic effect of melatonin might be corroborated by
      significantly elevated salivary melatonin levels directly after nocturnal tonic
      clonic seizure which affected patients with highest concentration of this hormone
      at 2a.m. These observations would need confirmation based on studies of larger
      groups of epileptic patients.

PMID- 24905530
TI  - Alpha lipoic acid protects the heart against myocardial post ischemia-reperfusion
      arrhythmias via KATP channel activation in isolated rat hearts.
AB  - The cardiovascular effects of alpha lipoic acid were evaluated in isolated rat
      hearts exposed to ischemia-reperfusion injury in vitro. Alpha-lipoic acid raised
      the level of sulfane sulfur playing an important role in the release of hydrogen
      sulfide. H2S was shown to prevent the post-reperfusion arrhythmias and to protect
      the cardiomyocytes from death caused by hypoxia. The activation of potassium ATP
      sensitive channels (K(ATP) channels) is one of the most important mechanisms of
      action of hydrogen sulfide in the cardiovascular system. The aim of this study
      was to investigate whether alpha lipoic acid can prevent the occurrence of post
      reperfusion arrhythmias in vitro using a Langendorff model of ischemia
      reperfusion in rats affecting the K(ATP) channels. Alpha lipoic acid
      significantly improved post-reperfusion cardiac function (reducing incidence of
      arrhythmias), especially in a dose of 10(-7)M. These cardiovascular effects of
      this compound on the measured parameters were reversed by glibenclamide, a
      selective K(ATP) blocker. Alpha lipoic acid increased the level of sulfane sulfur
      in the hearts. This may suggest that the positive effects caused by alpha lipoic
      acid in the cardiovascular system are not only related to its strong antioxidant
      activity, and the influence on the activity of such enzymes as aldehyde
      dehydrogenase 2, as previously suggested, but this compound can affect K(ATP)
      channels. It is possible that this indirect effect of alpha lipoic acid is
      connected with changes in the release of sulfane sulfur and hydrogen sulfide.

PMID- 24905531
TI  - 7-3-Chlorophenypiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione as a
      serotonin receptor ligands with potential antidepressant activity.
AB  - BACKGROUND: The previous study showed that arylpiperazine can condition affinity
      to alpha-adrenoceptors, 5-HT1A/5-HT2A receptors and compounds with arylpiperazine
      had antidepressant-like effect. The aim of this study was to determine the
      antidepressant-like activity of new arylpiperazines containing novel 8-alkoxy
      purine-2,6-dione fragments. METHODS: New 3-chloroarylpiperazinylalkyl analogs of
      8-alkoxy-purine-2,6-dione and their purine-2,6,8-trione analogs (2-5) were tested
      for their alpha1, alpha2, 5-HT1A,5-HT2A, and 5-HT7 receptor affinities in
      radioreceptor binding study. Moreover, in search for potential antidepressant
      properties of these compounds, the forced swim test in mice was conducted.
      RESULTS: Compounds 2 and 3 were potent 5-HT1A receptor ligands with Ki within the
      range on 12-15 nM. All investigated compounds were found to be highly active 5
      HT2A receptor (Ki 15-28 nM) and alpha1 adrenoceptor (Ki 21-89 nM) ligands. In the
      forced swim test all the compounds showed a significantly activity in spite of
      their reducing ability of locomotor activity. The most potent effect was produced
      by compound 4 and 5, which reduced the immobility time in this test in all used
      doses. CONCLUSION: In our study the most potent antidepressant-like activity was
      produced by compounds 4 and 5, which are selective for the 5-HT2A and alpha1
      receptors.

PMID- 24905532
TI  - The relationship between plasma concentration of metoprolol and CYP2D6 genotype
      in patients with ischemic heart disease.
AB  - BACKGROUND: Metoprolol is the one of the most commonly used beta-blockers in the
      treatment of ischemic heart disease and it is extensively metabolized in the
      liver undergoing oxidation by CYP2D6 isoenzyme of cytochrome P450. Gene encoding
      the CYP2D6 enzyme is characterized by genetic polymorphism. The CYP2D6 oxidation
      polymorphism has a major impact on the effectiveness and safety of the treatment.
      The aim of the study was to evaluate the relationship between plasma
      concentration of metoprolol and the CYP2D6 genotype in patients with ischemic
      heart disease. METHODS: Fifty patients were interviewed and subsequently enrolled
      into the study. The patients received metoprolol twice daily at a dose of 50mg.
      The blood samples were analyzed for two major defective alleles for CYP2D6 -
      CYP2D6*4 and CYP2D6*3--by the polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method. Metoprolol concentration in plasma was
      determined by using the new and unique high-performance liquid chromatography
      (HPLC) method in the author's own modification with Corona CAD detector (Charged
      Aerosol Detection). RESULTS: In the test group, genotypes conditioning poor
      oxidation (PM) occurred in 3 patients (6%), while 47 patients (94%) had genotypes
      coding for extensive metabolism (EM). Patients with PM genotypes had
      significantly higher plasma concentrations of metoprolol than the patients with
      EM genotype (mean 92.25 +/- SD 36.78 ng/ml vs. mean 168.22 +/- SD 5.61 ng/ml,
      respectively). Established relationships were statistically significant (NIR
      test, p=0.0009). CONCLUSIONS: This study demonstrated that the CYP2D6 genotype
      remains a major determinant of the metoprolol plasma concentrations. The
      pharmacogenetic effect is likely to have consequences on both, the clinical
      benefit of metoprolol treatment and adverse drug reactions. The use of Corona CAD
      detector seems to be a very good alternative method for the determination of
      metoprolol concentration in plasma.

PMID- 24905533
TI  - Chalcones derivatives as potent Cell division cycle 25B phosphatase inhibitors.
AB  - To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the
      mechanisms of inhibition in cancer cells. Nineteen 2'-hydroxy-4'
      isoprenyloxychalcone derivatives (a-s) were evaluated the inhibition CDC25B
      activity. The enzymatic activities of the CDC25B catalytic domain were determined
      by monitoring the dephosphorylation of OMFP. Cell growth inhibition was detected
      by MTT assay. The results showed that sixteen compounds significantly inhibited
      cycle 25B phosphatase in vitro. Among, three compounds k, r and s had the best
      inhibition activity and significantly inhibited CDC25B with inhibition rates
      against CDC25B of 99.95%, 99.75%, and 97.77%, respectively, which is similar to
      the reference drugs Na3VO4 (98%). Cytotoxic activity assays showed compounds k
      and r are the potent against HCT116, HeLa, and A549 cells, moreover, compound k
      delayed the potent tumor inhibitory activity in a colo205 xenograft model in
      vivo. 

PMID- 24905534
TI  - Risk of bias and brand explain the observed inconsistency in trials on
      glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo
      controlled trials.
AB  - OBJECTIVE: To determine whether study sponsor, chemical formulation, brand of
      glucosamine, and/or risk of bias explain observed inconsistencies in trials of
      glucosamine's efficacy for treating pain in osteoarthritis (OA). METHODS: A
      systematic review and stratified meta-analysis of randomized placebo-controlled
      trials was performed, and random-effects models were applied with inconsistency
      (I(2) ) and heterogeneity (tau(2) ) estimated using Review Manager and SAS,
      respectively. The major outcome was reduction of pain; the standardized mean
      difference (SMD [95% confidence interval (95% CI)]) served as effect size.
      RESULTS: The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine
      moderately reduced pain (SMD -0.51 [95% CI -0.72, -0.30]), although a high level
      of between-trial inconsistency was observed (I(2) = 88%). The single most
      important explanation (i.e., covariate) was brand, reducing heterogeneity by 41%
      (P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product
      resulted in significant pain reduction (SMD -1.07 [95% CI -1.47, -0.67]),
      although a sensitivity analysis of 3 low risk of bias trials using the
      Rottapharm/Madaus product showed less promising results (SMD -0.27 [95% CI -0.43,
      -0.12]), which is only a small effect size. Thirteen trials (1,963 patients)
      using non-Rottapharm/Madaus products consistently failed to show a reduction in
      pain (SMD -0.11 [95% CI -0.46, 0.24]). The second most important explanation was
      overall risk of bias (reducing heterogeneity by 32%). CONCLUSION: Most of the
      observed heterogeneity in glucosamine trials is explained by brand. Trials using
      the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA
      compared to other preparations of glucosamine. Large inconsistency was found,
      however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a
      small effect size.

PMID- 24905535
TI  - The lack of upstream elements of the Cek1 and Hog1 mediated pathways leads to a
      synthetic lethal phenotype upon osmotic stress in Candida albicans.
AB  - Different signal transduction pathways mediated by MAP kinases have been
      described in Candida albicans. These pathways sense different stimuli and,
      therefore, elaborate specific responses. Hog1 was identified as the MAPK that is
      primarily involved in stress response and virulence, while Cek1 was more specific
      to cell wall biogenesis, mating and biofilm formation. In the present work,
      mutants defective in both pathways have been characterized under osmotic stress.
      Both routes are required for a full response against high osmotic challenge,
      since mutants defective in both pathways displayed aberrant morphology, cell
      polarity defects and abnormal chitin deposition, which correlate with loss of
      viability and appearance of apoptotic markers. These alterations occurred in
      spite of proper Hog1 and Cek1 phosphorylation and increased intra-cellular
      glycerol accumulation. The relevance of both routes in virulence is shown as ssk1
      msb2 sho1 opy2 mutants are avirulent in a mouse systemic model of infection and
      display reduced virulence in the Galleria mellonella model. 

PMID- 24905536
TI  - Occult retinal detachment after mild traumatic brain injury: case report and
      literature review.
AB  - Concussions, or mild traumatic brain injuries (mTBI), are on the forefront of
      sports medicine. There is a spectrum of symptoms associated with mTBI, some of
      which include blurriness, double vision, and light sensitivity. Further
      evaluation for nonconcussion-related causes is warranted if vision changes do not
      improve concurrently with other symptoms. Keeping in mind other less obvious
      injuries, including retinal detachment, is important when performing an initial
      evaluation or follow-up of an mTBI.

PMID- 24905538
TI  - Utilization of a text-messaging robot to assess intraday variation in concussion
      symptom severity scores.
AB  - OBJECTIVE: To determine the amount of within-day variation of Concussion Symptom
      Severity Scores (CSSSs) in athletes with a clinically diagnosed concussion.
      DESIGN: This prospective cohort study used a text-messaging robot to survey
      concussed athletes using the CSSS 5-times daily while they remained symptomatic.
      SETTING: Academic sports concussion clinic at a large tertiary care medical
      center. PARTICIPANTS: Fourteen 14- to 22-year-old athletes with clinically
      diagnosed concussions were enrolled. All were injured in sport, still in season,
      English speaking, and used a cellular telephone to text message on a regular
      basis. ASSESSMENT OF RISK FACTORS: This study did not collect any demographic or
      other information about the subjects. The only data collected were the individual
      responses to the questions in the Post Concussion Symptom Score (PCSS). The only
      aim of this study was to evaluate the variability in responses to the CSSS, which
      is calculated from the PCSS. MAIN OUTCOME MEASUREMENTS: The primary outcome
      measure was a repeatability coefficient from a random-effects model. Concussion
      Symptom Severity Score, mean daily CSSS, and standard deviation of CSSS
      differences from the mean were also calculated. RESULTS: Mean follow-up was 23.9
      days. A total of 24 180 text messages were received from subjects. Eight hundred
      four complete surveys were analyzed. Repeatability coefficient was +/-23.1.
      CONCLUSIONS: When surveyed frequently by a text-messaging robot, concussed
      athletes report poorly repeatable Sport Concussion Assessment Tool 2 (SCAT2)
      Symptom Severity Scores. CLINICAL RELEVANCE: The SCAT2 Symptom Severity Score may
      be an invalid method of tracking concussion severity and resolution over time.

PMID- 24905537
TI  - Risk of athletes with Chiari malformations suffering catastrophic injuries during
      sports participation is low.
AB  - OBJECTIVE: To estimate the risk of athletes with Chiari malformations sustaining
      a catastrophic injury. DESIGN: Retrospective, descriptive cohort study.
      PARTICIPANTS: All patients diagnosed with Chiari malformation at our institution
      between June 2008 and November 2011. ASSESSMENT OF RISK FACTORS: Participants
      were mailed a questionnaire regarding the number of seasons they participated in
      organized athletics. Magnetic resonance images were reviewed to describe the
      characteristics of respondent's Chiari malformations. MAIN OUTCOME MEASURES:
      Whether or not the patient had sustained an injury resulting in death, coma, or
      paralysis. RESULTS: We had a 53% (N = 147) response rate. Respondents were of a
      mean age of 15 years (SD, 2 years) at the time of diagnosis. The mean length of
      protrusion of the cerebellar tonsils below the foramen magnum was 11.2 mm (SD,
      5.7 mm). Most of the respondents had pointed cerebellar tonsils and some degree
      of crowding within the foramen magnum. During a total of 1627 athletic seasons
      played by patients with Chiari malformation, 0 respondents [95% confidence
      interval (CI), 0.0000-0.0023] sustained an injury resulting in death, coma, or
      paralysis. Likewise, during 191 collision sport athletic seasons, 0 (95% CI,
      0.0000-0.0191) respondents sustained an injury resulting in death, coma, or
      paralysis. CONCLUSIONS: The risk of athletes with Chiari malformations suffering
      catastrophic injuries during sports participation is low. This estimate of risk
      should be considered when making return-to-play decisions. Given the variability
      of anatomical consideration for patients with Chiari malformations, however, each
      return-to-play decision must continue to be made on a case-by-case basis,
      considering all of the available information. CLINICAL RELEVANCE: The low risk of
      athletes with Chiari malformations suffering catastrophic injuries in sports
      should be considered when making return-to-play decisions.

PMID- 24905539
TI  - Validation of a virtual reality balance module for use in clinical concussion
      assessment and management.
AB  - OBJECTIVE: To determine the criterion and content validity of a virtual reality
      (VR) balance module for use in clinical practice. DESIGN: Retrospective, VR
      balance module completed by participants during concussion baseline or assessment
      testing session. SETTING: A Pennsylvania State University research laboratory.
      PARTICIPANTS: A total of 60 control and 28 concussed students and athletes from
      the Pennsylvania State University. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      This study examined: (1) the relationship between VR composite balance scores
      (final, stationary, yaw, pitch, and roll) and area of the center-of-pressure
      (eyes open and closed) scores and (2) group differences (normal volunteers and
      concussed student-athletes) on VR composite balance scores. RESULTS: With the
      exception of the stationary composite score, all other VR balance composite
      scores were significantly correlated with the center of pressure data obtained
      from a force platform. Significant correlations ranged from r = -0.273 to -0.704
      for the eyes open conditions and from r = -0.353 to -0.876 for the eyes closed
      condition. When examining group differences on the VR balance composite modules,
      the concussed group did significantly (P < 0.01) worse on all measures compared
      with the control group. CONCLUSIONS: The VR balance module met or exceeded the
      criterion and content validity standard set by the current balance tools and may
      be appropriate for use in a clinical concussion setting. CLINICAL RELEVANCE:
      Virtual reality balance module is a valid tool for concussion assessment in
      clinical settings. This novel type of balance assessment may be more sensitive to
      concussion diagnoses, especially later (7-10 days) in the recovery phase than
      current clinical balance tools.

PMID- 24905540
TI  - Acute phototoxic reaction in a century cyclist.
AB  - Medications can cause photosensitivity. Several of these medications,
      specifically the nonsteroidal anti-inflammatory medications (NSAIDs), may be
      taken by athletes to treat joint and muscle discomfort. Many athletic events
      occur outdoors, which in turn exposes athletes to sunlight. Athletes taking
      NSAIDs and performing extensive outdoor activities may be at higher risk for
      phototoxic drug reactions. Clinicians may wish consider the potential for patient
      photosensitivity when recommending prescription and non-prescription medications
      to outdoor athletes.

PMID- 24905541
TI  - Comparison of isokinetic hip abduction and adduction peak torques and ratio
      between sexes.
AB  - OBJECTIVE: To evaluate hip abductor and adductor peak torque outputs and compare
      their ratios between sexes. DESIGN: A cross-sectional laboratory-controlled
      study. SETTING: Participants visited a laboratory and performed an isokinetic hip
      abductor and adductor test. All participants performed 2 sets of 5 repetitions of
      concentric hip abduction and adduction in a standing position at 60 degrees per
      second. Gravity was determined as a function of joint angle relative to the
      horizontal plane and was corrected by normalizing the weight of the limb on an
      individual basis. PARTICIPANTS: A total of 36 collegiate athletes. INDEPENDENT
      VARIABLES: Sex (20 females and 16 males). MAIN OUTCOME MEASURES: Bilateral peak
      hip abductor and adductor torques were measured. The 3 highest peak torque values
      were averaged for each subject. RESULTS: Independent t tests were used to compare
      sex differences in hip abductor and adductor peak torques and the
      abductor:adductor peak torque ratios. Males demonstrated significantly greater
      hip abductor peak torque compared with females (males 1.29 +/- 0.24 Nm/kg,
      females 1.13 +/- 0.20 Nm/kg; P = 0.03). Neither hip adductor peak torque nor
      their ratios differed between sexes. CONCLUSIONS: Sex differences in hip abductor
      strength were observed. The role of weaker hip abductors in females deserves
      further attention and may be a factor for higher risk of knee pathologies.

PMID- 24905543
TI  - Haemorrhagic toxin and lethal toxin from Clostridium sordellii strain vpi9048:
      molecular characterization and comparative analysis of substrate specificity of
      the large clostridial glucosylating toxins.
AB  - Large clostridial glucosylating toxins (LCGTs) are produced by toxigenic strains
      of Clostridium difficile, Clostridium perfringens, Clostridium novyi and
      Clostridium sordellii. While most C. sordellii strains solely produce lethal
      toxin (TcsL), C. sordellii strain VPI9048 co-produces both hemorrhagic toxin
      (TcsH) and TcsL. Here, the sequences of TcsH-9048 and TcsL-9048 are provided,
      showing that both toxins retain conserved LCGT features and that TcsL and TcsH
      are highly related to Toxin A (TcdA) and Toxin B (TcdB) from C. difficile strain
      VPI10463. The substrate profile of the toxins was investigated with recombinant
      LCGT transferase domains (rN) and a wide panel of small GTPases. rN-TcsH-9048 and
      rN-TcdA-10463 glucosylated preferably Rho-GTPases but also Ras-GTPases to some
      extent. In this respect, rN-TcsH-9048 and rN-TcdA-10463 differ from the
      respective full-length TcsH-9048 and TcdA-10463, which exclusively glucosylate
      Rho-GTPases. rN-TcsL-9048 and full length TcsL-9048 glucosylate both Rho- and Ras
      GTPases, whereas rN-TcdB-10463 and full length TcdB-10463 exclusively glucosylate
      Rho-GTPases. Vero cells treated with full length TcsH-9048 or TcdA-10463 also
      showed glucosylation of Ras, albeit to a lower extent than of Rho-GTPases. Thus,
      in vitro analysis of substrate spectra using recombinant transferase domains
      corresponding to the auto-proteolytically cleaved domains, predicts more
      precisely the in vivo substrates than the full length toxins. Except for TcdB
      1470, all LCGTs evoked increased expression of the small GTPase RhoB, which
      exhibited cytoprotective activity in cells treated with TcsL isoforms, but pro
      apoptotic activity in cells treated with TcdA, TcdB, and TcsH. All LCGTs induced
      a rapid dephosphorylation of pY118-paxillin and of pS144/141-PAK1/2 prior to
      actin filament depolymerization indicating that disassembly of focal adhesions is
      an early event leading to the disorganization of the actin cytoskeleton. 

PMID- 24905544
TI  - Embodied free will beliefs: some effects of physical states on metaphysical
      opinions.
AB  - The present research suggests that people's bodily states affect their beliefs
      about free will. People with epilepsy and people with panic disorder, which are
      disorders characterized by a lack of control over one's body, reported less
      belief in free will compared to people without such disorders (Study 1). The more
      intensely people felt sexual desire, physical tiredness, and the urge to urinate,
      the less they believed in free will (Study 2). Among non-dieters, the more
      intensely they felt hunger, the less they believed in free will. However, dieters
      showed a trend in the opposite direction (Study 3). 

PMID- 24905542
TI  - Mechanisms of acetaminophen-induced cell death in primary human hepatocytes.
AB  - Acetaminophen (APAP) overdose is the most prevalent cause of drug-induced liver
      injury in western countries. Numerous studies have been conducted to investigate
      the mechanisms of injury after APAP overdose in various animal models; however,
      the importance of these mechanisms for humans remains unclear. Here we
      investigated APAP hepatotoxicity using freshly isolated primary human hepatocytes
      (PHH) from either donor livers or liver resections. PHH were exposed to 5mM, 10mM
      or 20mM APAP over a period of 48 h and multiple parameters were assessed. APAP
      dose-dependently induced significant hepatocyte necrosis starting from 24h, which
      correlated with the clinical onset of human liver injury after APAP overdose.
      Interestingly, cellular glutathione was depleted rapidly during the first 3h.
      APAP also resulted in early formation of APAP-protein adducts (measured in whole
      cell lysate and in mitochondria) and mitochondrial dysfunction, indicated by the
      loss of mitochondrial membrane potential after 12h. Furthermore, APAP time
      dependently triggered c-Jun N-terminal kinase (JNK) activation in the cytosol and
      translocation of phospho-JNK to the mitochondria. Both co-treatment and post
      treatment (3h) with the JNK inhibitor SP600125 reduced JNK activation and
      significantly attenuated cell death at 24h and 48h after APAP. The clinical
      antidote N-acetylcysteine offered almost complete protection even if administered
      6h after APAP and a partial protection when given at 15 h. CONCLUSION: These data
      highlight important mechanistic events in APAP toxicity in PHH and indicate a
      critical role of JNK in the progression of injury after APAP in humans. The JNK
      pathway may represent a therapeutic target in the clinic.

PMID- 24905545
TI  - Modelling unsupervised online-learning of artificial grammars: linking implicit
      and statistical learning.
AB  - Humans rapidly learn complex structures in various domains. Findings of above
      chance performance of some untrained control groups in artificial grammar
      learning studies raise questions about the extent to which learning can occur in
      an untrained, unsupervised testing situation with both correct and incorrect
      structures. The plausibility of unsupervised online-learning effects was modelled
      with n-gram, chunking and simple recurrent network models. A novel evaluation
      framework was applied, which alternates forced binary grammaticality judgments
      and subsequent learning of the same stimulus. Our results indicate a strong
      online learning effect for n-gram and chunking models and a weaker effect for
      simple recurrent network models. Such findings suggest that online learning is a
      plausible effect of statistical chunk learning that is possible when
      ungrammatical sequences contain a large proportion of grammatical chunks. Such
      common effects of continuous statistical learning may underlie statistical and
      implicit learning paradigms and raise implications for study design and testing
      methodologies. 

PMID- 24905546
TI  - Bottom-up or top-down in dream neuroscience? A top-down critique of two bottom-up
      studies.
AB  - Recent neuroscientific studies of dreaming, specifically those in relation to
      waking sensory-motor impairments, but also more generally, betray a faulty
      understanding of the sort of process that dreaming is. They adhere to the belief
      that dreaming is a bottom-up phenomenon, whose form and content is dictated by
      sensory-motor brain stem activity, rather than a top-down process initiated and
      controlled by higher-level cognitive systems. But empirical data strongly support
      the latter alternative, and refute the conceptualization and interpretation of
      recent studies of dreaming in sensory-motor impairment in particular and of
      recent dream neuroscience in general. 

PMID- 24905547
TI  - Practitioner review: Long-term pharmacological treatment of pediatric bipolar
      disorder.
AB  - BACKGROUND: Although long-term treatment is a core aspect of the management of
      children and adolescents with bipolar disorder (BD), most clinical
      recommendations are based on results from short-term studies or adult data. In
      order to guide clinical practice, we review the efficacy and safety profile of
      mood stabilizers, antipsychotics, and other pharmacological strategies for the
      long-term treatment of BD in pediatric patients. METHODS: A MEDLINE, EMBASE,
      Cochrane and PsycInfo search (inception through November 2013) was performed to
      identify prospective studies longer than 12 weeks assessing the use of
      pharmacological strategies for the long-term treatment of BD in pediatric
      patients (0-18 years of age). RESULTS: Four randomized controlled trials (RCT)
      [three placebo-controlled (assessing aripiprazole (2) and flax oil), and one head
      to-head comparison of lithium vs. divalproex], and thirteen noncontrolled studies
      (six open-label studies assessing lithium or anticonvulsants, five assessing
      second-generation antipsychotics (SGAs) and four assessing combination
      strategies) were included in the review. Aripiprazole has shown efficacy for
      relapse prevention in children with pediatric bipolar disorder (PBD) 4-9 years of
      age in one placebo-controlled RCT. Positive results have been reported in
      noncontrolled studies with quetiapine and lithium for relapse prevention, as well
      as with lithium, quetiapine, ziprasidone, and the combination of risperidone and
      divalproex or lithium for long-term symptom reduction in PBD. The most frequently
      reported adverse events in children and adolescents treated with lithium and
      anticonvulsants are gastrointestinal and neurological, whereas use of SGAs is
      mainly related to weight gain and sedation. CONCLUSION: According to the limited
      empirical evidence, aripiprazole can be useful for relapse prevention in children
      with PBD. Given the lack of consistent efficacy data, clinical decision making
      should be based on individual clinical aspects and safety concerns.

PMID- 24905548
TI  - RIFAMPICIN: an antibiotic with brain protective function.
AB  - Besides its well known antibiotic activity rifampicin exerts multiple brain
      protective functions in acute cerebral ischemia and chronic neurodegeneration.
      The present mini-review gives an update of the unique activity of rifampicin in
      different diseases including Parkinson's disease, meningitis, stroke, Alzheimer's
      disease and optic nerve injury. 

PMID- 24905549
TI  - The O-specific polysaccharide of the marine bacterium Rheinheimera pacifica KMM
      1406T containing D- and L-2-acetamido-2-deoxy-galacturonic acids.
AB  - The O-specific polysaccharide was isolated from the lipopolysaccharide of
      Rheinheimera pacifica KMM 1406T and studied by chemical methods along with 1H and
      13C NMR spectroscopy. It was shown that the polysaccharide contains one residue
      each of 2-acetamido-2-deoxy-D-galactose (D-GalNAc), 2-acetamido-2-deoxy-D- and 2
      acetamido-2-deoxy-L-galacturonic acids (D-GalNAcA, L-GalNAcA), 2,4-diacetamido
      2,4,6-trideoxy-D-glucose (D-QuiNAc4NAc), and 4-(N-acetyl-D-alanyl)amino-4,6
      dideoxy-D-glucose (D-Qui4NAlaAc) and has the following structure: ->4)-alpha-D
      GalpNAc-(1->4)-alpha-L-GalpNAcA-(1->3)-beta-D-QuipNAc4NAc-(1->2)-beta-D
      Quip4NDAlaAc-(1->4)-alpha-D-GalpNAcA-(1->

PMID- 24905550
TI  - New ureas containing glycosyl and diphenylphosphinyl scaffolds: synthesis and the
      first attempts to use them in asymmetric synthesis.
AB  - Chiral ureas containing glycosyl and diphenylphosphinyl scaffolds were found to
      be an effective organocatalyst. They were synthesised in high yields by a one-pot
      tandem Staudinger/aza-Wittig coupling reaction. The first attempts of using them
      in asymmetric synthesis are presented. Yields of the Morita-Baylis-Hillman
      reaction were moderate with an enantiomeric excess of up to 80%. 

PMID- 24905551
TI  - Heat, heat waves, and hospital admissions among the elderly in the United States,
      1992-2006.
AB  - BACKGROUND: Heat-wave frequency, intensity, and duration are increasing with
      global climate change. The association between heat and mortality in the elderly
      is well documented, but less is known regarding associations with hospital
      admissions. OBJECTIVES: Our goal was to determine associations between moderate
      and extreme heat, heat waves, and hospital admissions for nonaccidental causes
      among Medicare beneficiaries >= 65 years of age in 114 cities across five U.S.
      climate zones. METHODS: We used Medicare inpatient billing records and city
      specific data on temperature, humidity, and ozone from 1992 through 2006 in a
      time-stratified case-crossover design to estimate the association between
      hospitalization and moderate [90th percentile of apparent temperature (AT)] and
      extreme (99th percentile of AT) heat and heat waves (AT above the 95th percentile
      over 2-8 days). In sensitivity analyses, we additionally considered confounding
      by ozone and holidays, different temperature metrics, and alternate models of the
      exposure-response relationship. RESULTS: Associations between moderate heat and
      hospital admissions were minimal, but extreme heat was associated with a 3% (95%
      CI: 2%, 4%) increase in all-cause hospital admissions over the subsequent 8 days.
      In cause-specific analyses, extreme heat was associated with increased
      hospitalizations for renal (15%; 95% CI: 9%, 21%) and respiratory (4%; 95% CI:
      2%, 7%) diseases, but not for cardiovascular diseases. An added heat-wave effect
      was observed for renal and respiratory admissions. CONCLUSION: Extreme heat is
      associated with increased hospital admissions, particularly for renal causes,
      among the elderly in the United States.

PMID- 24905552
TI  - Tension force-induced ATP promotes osteogenesis through P2X7 receptor in
      osteoblasts.
AB  - Orthodontic tooth movement induces alveolar bone resorption and formation by
      mechanical stimuli. Force exerted on the traction side promotes bone formation.
      Adenosine triphosphate (ATP) is one of the key mediators that respond to bone
      cells by mechanical stimuli. However, the effect of tension force (TF)-induced
      ATP on osteogenesis is inadequately understood. Accordingly, we investigated the
      effect of TF on ATP production and osteogenesis in MC3T3-E1 cells. Cells were
      incubated in the presence or absence of P2X7 receptor antagonist A438079, and
      then stimulated with or without cyclic TF (6% or 18%) for a maximum of 24 h using
      Flexercell Strain Unit 3000. TF significantly increased extracellular ATP release
      compared to control. Six percent TF had maximum effect on ATP release compared to
      18% TF and control. Six percent TF induced the expression of Runx2 and Osterix.
      Six percent TF also increased the expression of extracellular matrix proteins
      (ECMPs), ALP activity, and the calcium content in ECM. A438079 blocked the
      stimulatory effect of 6% TF on the expression of Runx2, Osterix and ECMPs, ALP
      activity, and calcium content in ECM. This study indicated that TF-induced
      extracellular ATP is released in osteoblasts, suggesting that TF-induced ATP
      promotes osteogenesis by autocrine action through P2X7 receptor in osteoblasts.

PMID- 24905553
TI  - Incidence and clinical features of acute rheumatic fever in Kayseri, Central
      Anatolia, 1998-2011.
AB  - BACKGROUND: In developing countries, acute rheumatic fever is the most common
      cause of acquired heart disease in the paediatric and adolescent population. It
      is believed that vulnerability to developing acute rheumatic fever is associated
      with several factors such as socio-economic and living conditions. Aim Determine
      the incidence and clinical characteristics of acute rheumatic fever in the
      Central Anatolia region of Kayseri within the last 14 years, and to make a
      comparison of two 7-year periods. Material and methods We performed a
      retrospective analysis of 624 patients who were diagnosed with acute rheumatic
      fever at the Department of Pediatric Cardiology in the Medical Faculty of Erciyes
      University between January, 1998 and December, 2011. RESULTS: The mean age of
      patients was 10.9+/-2.7 years. The female/male ratio was 1.4. When patients were
      categorised according to age groups, the largest group represented 376 patients
      (60.3%) aged between 10 and 14 years. The estimated incidence rate of acute
      rheumatic fever was 7.4/100,000 in the Central Anatolia region of Kayseri. Among
      the major findings, the most common included carditis at 54%, arthritis at 35%,
      Sydenham's chorea at 25%, and subcutaneous nodules at 0.5%, respectively. No
      significant difference was found between the first 7-year period and second 7
      year period in distributions of age, gender, and major findings. CONCLUSION:
      Although there has been socio-economic development in Turkey in the recent years,
      the incidence of acute rheumatic fever is still high in the Central Anatolia
      region of Kayseri.

PMID- 24905554
TI  - Real world comparison of the MGuard Stent versus the bare metal stent for ST
      elevation myocardial infarction (the REWARD-MI study).
AB  - AIM: The MGuard Stent (MGS) was designed to prevent distal embolization of
      thrombus and has been shown to improve microcirculation in ST-elevation
      myocardial infarction (STEMI). However, there are no real world data comparing it
      with the bare metal stent (BMS). The aim of this study is to determine the
      efficacy and safety of the MGS in STEMI in the real world compared to the BMS.
      METHODS AND RESULTS: In total, 262 patients were included from a single centre,
      of which 35.9% had an MGS implanted. Two groups of 79 patients were established
      after propensity score matching, and they were similar in terms of baseline and
      periprocedural variables. The mean follow-up was 321 +/- 12.94 days. There was no
      difference in mortality (7.6% in both groups), major adverse cardiac events
      (20.3% vs. 12.7%, P = 0.198), non-cardiac mortality, or non-fatal myocardial
      infarction (6.3% in both groups). Target lesion revascularization (TLR) was
      significantly higher in the MGS group (11.4% (9) vs. 1.3% (1) P < 0.01; RR 10.02
      [1.23-81.16]). CONCLUSION: Our study is the first to compare the MGS with the BMS
      in STEMI in the real world, and it also appears to confirm that although the MGS
      is a safe device in STEMI that is not associated with increased mortality, it is
      associated with a higher long-term TLR rate. (c) 2014 Wiley Periodicals, Inc.

PMID- 24905555
TI  - Metal-catalyzed reductive coupling reactions of organic halides with carbonyl
      type compounds.
AB  - Metal-catalyzed reductive coupling reactions of aryl halides and (pseudo)halides
      with carbonyl-type compounds have undergone an impressive development within the
      last years. These methodologies have shown to be a powerful alternate strategy,
      practicality aside, to the use of stoichiometric, well-defined, and, in some
      cases, air-sensitive organometallic species. In this Minireview, the recent
      findings in this field are summarized, with particular emphasis on the
      mechanistic interpretation of the results and future aspects of this area of
      expertise. 

PMID- 24905556
TI  - Deformation of the water/oil interface during the adsorption of sterically
      stabilized particles.
AB  - The adsorption of sterically stabilized colloids at water/oil (w/o) interfaces is
      studied experimentally by the formation of Pickering emulsions. Specifically, the
      effect of the steric stabilizer with respect to the rate of particle adsorption
      is investigated. Uniform, micrometer-sized poly(methyl methacrylate) (pMMA)
      particles, which are sterically stabilized with poly(isobutylene) (pIB), are
      used. The pIB concentration on the particle surface (GammaPIB) is controlled
      during the synthesis by adjusting the pIB/monomer ratio. Pickering emulsions are
      formed directly by the addition of water to the nonaqueous pMMA dispersions and
      subsequent emulsification. A strong dependence of the rate of particle adsorption
      on GammaPIB is found. The rate constant k for particle adsorption decays
      exponentially with GammaPIB, which suggest the use of a Boltzmann factor to model
      the experimentally found rate constants. The experimental results can be
      explained when the activation barrier for particle adsorption EA is of the same
      order as the average kinetic energy EK of a particle colliding with an emulsion
      droplet, which is equivalent to 10(5) kBT. Interestingly, this makes EA several
      orders of magnitude greater than the steric interaction with another particle. A
      possible mechanism that can lead to such a significant repulsive force is the
      inhibited drainage of solvent between the particle and o/w interface. Deformation
      of the o/w interface then occurs, when the solvent does not have time to drain,
      which results in a dramatic increase in the interfacial energy. This study
      identified the relevance of drainage in the formation of Pickering emulsions.

PMID- 24905558
TI  - Who prefers the 'cost-effectiveness ratio' prioritization approach in health-care
      decisions? Results of an empirical analysis.
AB  - BACKGROUND: The problem of resource scarcity has led to an on-going debate about
      priority setting in the health-care system. Prioritization via the economic-based
      cost-effectiveness ratio (CER), for example, is controversial and has many
      advocates as well as opponents. Hence, the aim of our research is to analyse the
      fairness consideration of the CER approach in comparison with other
      prioritization approaches and to investigate whether these preferences depend on
      the field of study. METHODS: We developed and tested a unique questionnaire.
      Between October 2011 and January 2012, freshmen and advanced university students
      of medicine, law, economics, philosophy and religion in Germany were asked to
      choose among four prioritization approaches (CER, minimum health, random
      selection and age) using a dichotomous choice technique. The data were analysed
      by descriptive and microeconometric regression techniques. RESULTS: Data on 913
      students were included in the study. A majority of the students prioritized cost
      effectiveness second after minimum health. Advanced economics students preferred
      the CER approach significantly more than did incoming economics students. The
      attitudes of the advanced philosophy/religion students towards the CER were
      significantly more negative compared with the respective freshmen. Further,
      gender had a strong, significant impact on attitudes: women chose the CER less
      often than men did (P < 0.01). CONCLUSION: The results of this study indicate
      that attitudes presented by opinion leaders in the investigated fields of study
      seem to be in line with the perceptions of the respective fields' advanced
      students. Because of these differences, the debate on how to deal with scarce
      resources may remain complicated.

PMID- 24905559
TI  - Running sprint interval training induces fat loss in women.
AB  - Data on whether sprint interval training (SIT) (repeated supermaximal intensity,
      short-duration exercise) affects body composition are limited, and the data that
      are available suggest that men respond more favourably than do women. Moreover,
      most SIT data involve cycling exercise, and running may differ because of the
      larger muscle mass involved. Further, running is a more universal exercise type.
      This study assessed whether running SIT can alter body composition (air
      displacement plethysmography), waist circumference, maximal oxygen consumption,
      peak running speed, and (or) the blood lipid profile. Fifteen recreationally
      active women (age, 22.9 +/- 3.6 years; height, 163.9 +/- 5.1 cm; mass, 60.8 +/-
      5.2 kg) completed 6 weeks of running SIT (4 to 6, 30-s "all-out" sprints on a
      self-propelled treadmill separated by 4 min of rest performed 3 times per week).
      Training decreased body fat mass by 8.0% (15.1 +/- 3.6 to 13.9 +/- 3.4 kg, P =
      0.002) and waist circumference by 3.5% (80.1 +/- 4.2 to 77.3 +/- 4.4 cm, P =
      0.048), whereas it increased fat-free mass by 1.3% (45.7 +/- 3.5 to 46.3 +/- 2.9
      kg, P = 0.05), maximal oxygen consumption by 8.7% (46 +/- 5 to 50 +/- 6
      mL/(kg.min), P = 0.004), and peak running speed by 4.8% (16.6 +/- 1.7 to 17.4 +/-
      1.4 km/h, P = 0.026). There were no differences in food intake assessed by 3-day
      food records (P > 0.329) or in blood lipids (P > 0.595), except for a slight
      decrease in high-density lipoprotein concentration (1.34 +/- 0.28 to 1.24 +/-
      0.24 mmol/L, P = 0.034). Running SIT is a time-efficient strategy for decreasing
      body fat while increasing aerobic capacity, peak running speed, and fat-free mass
      in healthy young women. 

PMID- 24905560
TI  - Quantifying accuracy and precision of diffusion MR tractography of the
      corticospinal tract in brain tumors.
AB  - OBJECT: The aim of this paper was to validate the diffusion tensor imaging (DTI)
      model for delineation of the corticospinal tract using cortical and subcortical
      white matter electrical stimulation for the location of functional motor
      pathways. METHODS: The authors compare probabilistic versus deterministic DTI
      fiber tracking by reconstructing the pyramidal fiber tracts on preoperatively
      acquired DTI in patients with brain tumors. They determined the accuracy and
      precision of these 2 methods using subcortical stimulation points and the
      sensitivity using cortical stimulation points. The authors further explored the
      reliability of these methods by estimation of the potential that the found
      connections were due to a random chance using a novel neighborhood permutation
      method. RESULTS: The probabilistic tracking method delineated tracts that were
      significantly closer to the stimulation points and was more sensitive than
      deterministic DTI fiber tracking to define the tracts directed to the motor
      sites. However, both techniques demonstrated poor sensitivity to finding lateral
      motor regions. CONCLUSIONS: This study highlights the importance of the
      validation and quantification of preoperative fiber tracking with the aid of
      electrophysiological data during the surgery. The poor sensitivity of DTI to
      delineate lateral motor pathways reported herein suggests that DTI fiber tracking
      must be used with caution and only as adjunctive data to established methods for
      motor mapping.

PMID- 24905561
TI  - Clinical and radiological outcomes following traumatic Grade 1 and 2 vertebral
      artery injuries: a 10-year retrospective analysis from a Level 1 trauma center.
AB  - OBJECT: Screening of blunt vertebral artery (VA) injuries has increased since
      research has shown that they occur at a higher incidence than originally
      reported. Grade 1 and 2 injuries are the most common form of blunt VA injury.
      Proper screening, management, and follow-up of these injuries remain
      controversial. In this report, imaging, progression, treatment, and outcomes of
      Grade 1 and 2 blunt VA injuries were analyzed to better define their natural
      history and to establish a rational management plan based upon their risk of
      progression and cerebral infarct. METHODS: A retrospective review of all blunt
      traumatic carotid artery and VA injuries from December 2003 to April 2013 was
      performed. For the purposes of this report, focus was given to Grade 1 and 2 VA
      injuries. Grade 1 injuries were defined as a vessel lumen stenosis of less than
      25%, and Grade 2 injuries were defined as vessel lumen stenosis between 25% and
      50%. Demographic information, radiological imaging, number of images performed
      per individual, length of radiological follow-up, radiological outcome at the end
      of follow-up, treatment provided, and documentation of stroke or transient
      ischemic attack were recorded. RESULTS: One hundred eighty-seven Grade 1 and 2 VA
      injuries in 143 patients were identified. Of these 143 patients, 120 with 152
      Grade 1 or 2 blunt VA injuries were available for follow-up. The mean duration of
      follow-up was 40 days. Repeat imaging showed that 148 (97.4%) Grade 1 or 2 blunt
      VA injuries were stable, improved, or resolved on final follow-up imaging.
      Seventy-nine patients (66%) were treated with aspirin, whereas 35 patients (29%)
      received no treatment. The remaining patients were treated with other
      antiplatelet agents or anticoagulant medication. Neuroimaging demonstrated 2
      cases (1.7%) with posterior circulation infarcts that were believed to be related
      to their blunt VA injuries, both of which occurred during the initial
      hospitalization and within the first 4 days after injury. CONCLUSIONS: Although
      follow-up imaging showed progressive worsening without radiological improvement
      in only a small number of patients with low-grade blunt VA injuries, these
      findings did not correlate with adverse clinical outcome. The posttraumatic
      cerebral infarction rate of 1.7% may be overestimated, and the use of
      acetylsalicylic acid or other antiplatelet or anticoagulant medication did not
      correlate with radiological changes or rate of cerebral infarction. While these
      data suggest the possibility that these low-grade VA injuries may not require
      treatment or follow-up, future prospective studies are needed to make conclusive
      changes related to management.

PMID- 24905562
TI  - Emergent surgical embolectomy for middle cerebral artery occlusion due to carotid
      plaque rupture followed by elective carotid endarterectomy.
AB  - Embolic intracranial large artery occlusion with severe neurological deficit is
      associated with an extremely poor prognosis. The safest and most effective
      treatment strategy has not yet been determined when such emboli are associated
      with unstable proximal carotid plaque. The authors performed emergent surgical
      embolectomy for left middle cerebral artery (MCA) occlusion, and the patient
      experienced marked neurological recovery without focal deficit and regained
      premorbid activity. Postoperative investigation revealed "vulnerable plaque" of
      the left internal carotid artery without apparent evidence of cardiac embolism,
      such as would be seen with atrial fibrillation. Specimens from subsequent
      elective carotid endarterectomy (CEA) showed ruptured vulnerable plaque that was
      histologically consistent as a source of the intracranial embolic specimen.
      Surgical embolectomy for MCA occlusion due to carotid plaque rupture followed by
      CEA could be a safer and more effective alternative to endovascular treatment
      from the standpoint of obviating the risk of secondary embolism that could
      otherwise occur as a result of the manipulation of devices through an extremely
      unstable portion of plaque. Further, this strategy is associated with a high
      probability of complete recanalization with direct removal of hard and large,
      though fragile, emboli. 

PMID- 24905563
TI  - Virtual interactive presence for real-time, long-distance surgical collaboration
      during complex microsurgical procedures.
AB  - OBJECT: The shortage of surgeons compels the development of novel technologies
      that geographically extend the capabilities of individual surgeons and enhance
      surgical skills. The authors have developed "Virtual Interactive Presence" (VIP),
      a platform that allows remote participants to simultaneously view each other's
      visual field, creating a shared field of view for real-time surgical
      telecollaboration. METHODS: The authors demonstrate the capability of VIP to
      facilitate long-distance telecollaboration during cadaveric dissection. Virtual
      Interactive Presence consists of local and remote workstations with integrated
      video capture devices and video displays. Each workstation mutually connects via
      commercial teleconferencing devices, allowing worldwide point-to-point
      communication. Software composites the local and remote video feeds, displaying a
      hybrid perspective to each participant. For demonstration, local and remote VIP
      stations were situated in Indianapolis, Indiana, and Birmingham, Alabama,
      respectively. A suboccipital craniotomy and microsurgical dissection of the
      pineal region was performed in a cadaveric specimen using VIP. Task and system
      performance were subjectively evaluated, while additional video analysis was used
      for objective assessment of delay and resolution. RESULTS: Participants at both
      stations were able to visually and verbally interact while identifying anatomical
      structures, guiding surgical maneuvers, and discussing overall surgical strategy.
      Video analysis of 3 separate video clips yielded a mean compositing delay of 760
      +/- 606 msec (when compared with the audio signal). Image resolution was adequate
      to visualize complex intracranial anatomy and provide interactive guidance.
      CONCLUSIONS: Virtual Interactive Presence is a feasible paradigm for real-time,
      long-distance surgical telecollaboration. Delay, resolution, scaling, and
      registration are parameters that require further optimization, but are within the
      realm of current technology. The paradigm potentially enables remotely located
      experts to mentor less experienced personnel located at the surgical site with
      applications in surgical training programs, remote proctoring for proficiency,
      and expert support for rural settings and across different counties.

PMID- 24905564
TI  - Meta-analysis comparing deep brain stimulation of the globus pallidus and
      subthalamic nucleus to treat advanced Parkinson disease.
AB  - OBJECT: Deep brain stimulation (DBS) is the surgical procedure of choice for
      patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi)
      and the subthalamic nucleus (STN) are commonly targeted by this procedure. The
      purpose of this meta-analysis was to compare the efficacy of DBS in each region.
      METHODS: MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were
      searched for English-language studies published before April 2013. RESULTS: of
      studies investigating the efficacy and clinical outcomes of DBS of the GPi and
      STN for PD were analyzed. RESULTS: Six eligible trials containing a total of 563
      patients were included in the analysis. Deep brain stimulation of the GPi or STN
      equally improved motor function, measured by the Unified Parkinson's Disease
      Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off
      medication phases), within 1 year postsurgery. The change score for the on
      medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518
      patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p >
      0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living)
      scores for patients on medication improved equally in both DBS groups (p = 0.97).
      STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27
      316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by
      Beck Depression Inventory, 2nd edition scores, showed greater improvement from
      baseline after GPi DBS than after STN DBS (standardized mean difference -2.28,
      95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). CONCLUSIONS: GPi and
      STN DBS improve motor function and activities of daily living for PD patients.
      Differences in therapeutic efficacy for PD were not observed between the 2
      procedures. STN DBS allowed greater reduction in medication for patients, whereas
      GPi DBS provided greater relief from psychiatric symptoms. An understanding of
      other symptomatic aspects of targeting each region and long-term observations on
      therapeutic effects are needed.

PMID- 24905565
TI  - The emergent role of metabolic phenotyping in dynamic patient stratification.
AB  - The role that metabolic phenotyping can increasingly play in patient
      stratification and personalised medicine is discussed. The background to the
      general approach, comprehensive and simultaneous analysis of small-molecule
      metabolites in biofluids, tissues and tissue extracts combined with suitable
      multivariate statistical models, is summarised. The main techniques used (NMR and
      mass spectrometry) are cited, and the implementation of dedicated phenome centres
      is explained. Finally, the advantages and limitations, opportunities and
      drawbacks of the approach are discussed. 

PMID- 24905567
TI  - Predictors of Weight Loss for African-American Women in the Faith, Activity, and
      Nutrition (FAN) Study.
AB  - BACKGROUND: Understanding predictors of weight loss can assist in developing
      targeted evidence-based programs to reduce obesity in faith-based settings. The
      purpose of this study was to examine predictors of weight loss for a sample of
      African-American women taking part in in a church-based study. METHODS:
      Participants (N = 350) completed physical assessments and comprehensive surveys
      at baseline and 15 months later. Analyses examined baseline variables and change
      in variables from baseline to posttest, as predictors of >= 5% weight loss at
      posttest. Demographic, health-related, and behavioral variables were examined.
      RESULTS: Lower baseline stress predicted greater likelihood of weight loss.
      Increased leisure-time physical activity (LTPA) from baseline to posttest was
      predictive of greater weight loss. The odds of >= 5% weight loss was 38% lower
      for every 1-point increase in baseline stress (OR = 0.62, CI = 0.39, 0.98, P =
      .04) and 6% greater for every 1-hour increase in posttest LTPA (OR = 1.06, CI =
      1.0, 1.12, P = .049). CONCLUSIONS: Increased LTPA appears to be an independent
      predictor of modest but meaningful reductions in weight among African-American
      women. African-American women reporting higher levels of stress at baseline may
      require more intense strategies emphasizing increased LTPA to lose weight.

PMID- 24905566
TI  - Interferon tau alleviates obesity-induced adipose tissue inflammation and insulin
      resistance by regulating macrophage polarization.
AB  - Chronic adipose tissue inflammation is a hallmark of obesity-induced insulin
      resistance and anti-inflammatory agents can benefit patients with obesity
      associated syndromes. Currently available type I interferons for therapeutic
      immunomodulation are accompanied by high cytotoxicity and therefore in this study
      we have examined anti-inflammatory effects of interferon tau (IFNT), a member of
      the type I interferon family with low cellular toxicity even at high doses. Using
      a diet-induced obesity mouse model, we observed enhanced insulin sensitivity in
      obese mice administered IFNT compared to control mice, which was accompanied by a
      significant decrease in secretion of proinflammatory cytokines and elevated anti
      inflammatory macrophages (M2) in adipose tissue. Further investigations revealed
      that IFNT is a potent regulator of macrophage activation that favors anti
      inflammatory responses as evidenced by activation of associated surface antigens,
      production of anti-inflammatory cytokines, and activation of selective cell
      signaling pathways. Thus, our study demonstrates, for the first time, that IFNT
      can significantly mitigate obesity-associated systemic insulin resistance and
      tissue inflammation by controlling macrophage polarization, and thus IFNT can be
      a novel bio-therapeutic agent for treating obesity-associated syndromes and type
      2 diabetes. 

PMID- 24905568
TI  - Breakdown of continuum elasticity in amorphous solids.
AB  - We show numerically that the response of simple amorphous solids (elastic
      networks and particle packings) to a local force dipole is characterized by a
      lengthscale lc that diverges as unjamming is approached as lc ~ (z - 2d)(-1/2),
      where z >= 2d is the mean coordination, and d is the spatial dimension, at odds
      with previous numerical claims. We also show how the magnitude of the lengthscale
      lc is amplified by the presence of internal stresses in the disordered solid. Our
      data suggests a divergence of lc ~ (pc - p)(-1/4) with proximity to a critical
      internal stress pc at which soft elastic modes become unstable. 

PMID- 24905569
TI  - Monitoring (un)consciousness: the implications of a new definition of
      'anaesthesia'.

PMID- 24905572
TI  - A note on Conium maculatum L., the plant that defeated Alexander the Great.

PMID- 24905571
TI  - 'Crazy Monkey' poisons man and dog: Human and canine seizures due to PB-22, a
      novel synthetic cannabinoid.
AB  - CONTEXT: Synthetic cannabinoids have been manufactured, sold, and consumed for
      recreational purposes since at least 2004; their use has been associated with
      adverse psychiatric, cardiovascular, renal, pulmonary, and neurologic effects. We
      report simultaneous canine and human clinical cases associated with exposure to a
      novel synthetic cannabinoid, PB-22 (QUPIC). CASE REPORT: A 22-year-old man
      brought his dog to a veterinary clinic after it had a seizure. During the course
      of the canine's evaluation, the human patient was witnessed to have a generalized
      tonic-clonic seizure. He was intubated for agitation and combativeness after his
      arrival to the emergency department (ED). He was extubated the next day without
      discernable sequelae. The canine patient received intravenous hydration and was
      also discharged to home after a period of close observation. The man later
      endorsed smoking three containers of a substance called "Crazy Monkey" daily for
      several weeks, but would not disclose how his dog had been exposed. The
      convulsant effects of "Crazy Monkey" were confirmed in this patient when, three
      months later, he was sedated, paralyzed, intubated, and admitted to another local
      hospital for seizures in the context of smoking the same product. DISCUSSION:
      Laboratory analysis of samples obtained from the human and canine patients. A
      sample of the product (labeled "Crazy Monkey") revealed the presence of PB-22
      (QUPIC), a novel synthetic cannabinoid. Additionally, serum and urine samples
      from the human patient contained metabolites of a second compound, UR-144.
      CONCLUSION: We present a laboratory-confirmed case report of human and canine
      neurotoxicity associated with a novel synthetic cannabinoid, PB-22 (QUIPIC).

PMID- 24905573
TI  - Barium toxicity and the role of the potassium inward rectifier current.
AB  - INTRODUCTION: Barium is a stable divalent earth metal and highly toxic upon acute
      and chronic exposure. Barium is present in many products and involved in a number
      of industrial processes. Barium targets the potassium inward rectifier channels
      (IRCs) of the KCNJx gene family. Extracellular barium enters and strongly binds
      the potassium selectivity filter region resulting in blockade of the potassium
      conducting pore. IRCs are involved in numerous physiological processes of the
      human body and the most barium sensitive IRCs are highly expressed in all muscle
      types. OBJECTIVE: Our purpose was correlate to the clinical outcome of acute
      barium poisoning in man to current knowledge on IRC function. METHODOLOGY: The
      primary literature search was performed using Medline, Scopus and Google Scholar
      using search terms "barium AND poisoning"; "barium AND intoxication"; "barium AND
      case report" and retrieved publications from 1945 through 2012. Additional case
      reports were retrieved based on the reference lists of the primary hits.
      Duplicate publications, or publications presenting identical cases were omitted.
      A total of 39 case reports on acute barium poisoning containing 226 human
      subjects were identified for review. RESULTS: BaCO3 was the most frequent source
      and food the most frequent mode of poisoning. Patients suffered from
      gastrointestinal (vomiting, diarrhea), cardiovascular (arrhythmias,
      hypertension), neuromuscular (abnormal reflexes, paralysis), respiratory
      (respiratory arrest/failure) and metabolic (hypokalemia) symptoms. Severe
      hypokalemia (< 2.5 mM) was observed from barium serum concentrations greater than
      or equal to 0.0025 mM. Review of the ECG outcomes demonstrated ventricular
      extrasystoles, ST changes and profound U-waves to be associated strongly with
      poisoning. Most common treatment modalities were gastric lavage, oral sulfates,
      potassium i.v. and cardiorespiratory support. 27 patients (12%) died from barium
      poisoning. CONCLUSIONS: Barium is a potent, non-specific inhibitor of the
      potassium IRC current and affects all types of muscle at micromolar
      concentrations. Gastrointestinal symptoms frequently occur early in the course of
      barium poisoning. Hypokalemia resulting from an intracellular shift of potassium
      and the direct effect of barium at the potassium channels explain the cardiac
      arrhythmias and muscle weakness which commonly occur in barium poisoning.
      Treatment of barium poisoning is mainly supportive. Orally administered sulfate
      salts to form insoluble barium sulfate in the intestinal tract and potassium
      supplementation have potential but unproven benefit.

PMID- 24905570
TI  - Salinomycin suppresses LRP6 expression and inhibits both Wnt/beta-catenin and
      mTORC1 signaling in breast and prostate cancer cells.
AB  - Emerging evidence indicates that activation of Wnt/beta-catenin signaling at the
      cell surface results in inhibition of glycogen synthase kinase 3beta (GSK3beta),
      leading to activation of mTORC1 signaling in cancer cells. The low density
      lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for
      Wnt/beta-catenin signaling. Salinomycin is a novel small molecule inhibitor of
      LRP6. In the present study, we found that LRP6 overexpression induced mTORC1
      signaling activation in cancer cells, and that salinomycin was not only a potent
      Wnt/beta-catenin signaling inhibitor, but also a strong mTORC1 signaling
      antagonist in breast and prostate cancer cells. Mechanistically, salinomycin
      activated GSK3beta in cancer cells. Moreover, salinomycin was able to suppress
      the expression of cyclin D1 and survivin, two targets of both Wnt/beta-catenin
      and mTORC1 signaling, in prostate and breast cancer cells, and displayed
      remarkable anticancer activity. Our results present novel mechanisms underlying
      salinomycin-mediated cancer cell death.

PMID- 24905575
TI  - Viruses customize autophagy protein for efficient viral entry.
AB  - While the cell imposes multiple barriers to virus entry, enveloped viruses are
      remarkably still able to gain entry to their cellular hosts by hitchhiking and
      remodeling the endomembrane system to traffic within, and eventually escape from,
      endosomal organelles for their genome release. Elucidating viral entry mechanisms
      and their interaction with the host trafficking network is necessary for
      antiviral therapy. Here, we focus on the use of host autophagy molecular factors
      during the entry of prototypic negative-stranded RNA viruses, and highlight
      recent progress in our understanding of the role of one such factor, UVRAG, in
      both viral and cellular endocytic membrane trafficking and fusion events. 

PMID- 24905574
TI  - Streptococcus pneumoniae carriage prevalence in Nepal: evaluation of a method for
      delayed transport of samples from remote regions and implications for vaccine
      implementation.
AB  - BACKGROUND: Pneumococcal disease is a significant cause of morbidity and
      mortality in young children in Nepal, and currently available pneumococcal
      conjugate vaccines offer moderate coverage of invasive disease isolates. METHODS:
      A prevalence study of children aged 1.5 to 24 months in urban and rural Nepal was
      conducted. In the urban group, nasopharyngeal swabs (NPS) were transported using
      silica desiccant packages (SDP) with delayed processing (2 weeks), or skim-milk
      tryptone-glucose-glycerin (STGG) with immediate processing (within 8 hours).
      Pneumococcal nasopharyngeal carriage prevalence, serogroup/type distribution and
      isolate genotypes (as defined by multilocus sequence typing) were determined.
      RESULTS: 1101 children were enrolled into the study: 574 in the urban group and
      527 in the rural group. Overall carriage prevalence based on culture from
      specimens transported and stored in STGG was 58.7% (337/574), compared to 40.9%
      (235/574) in SDP. There was concordance of detection of pneumococcus in 67% of
      samples. Using the SDP method, pneumococcal carriage prevalence was higher in the
      rural population (69.2%; 364/526) compared to the urban population (40.9%;
      235/574). Serogroup/type distribution varied with geographical location. Over
      half of the genotypes identified in both the urban and rural pneumococcal
      populations were novel. CONCLUSION: The combination of delayed culture and
      transport using SDP underestimates the prevalence of pneumococcal carriage;
      however, in remote areas, this method could still provide a useful estimate of
      carriage prevalence and serogroup/type distribution. Vaccine impact is
      unpredictable in a setting with novel genotypes and limited serotype coverage as
      described here. Consequently, continued surveillance of pneumococcal isolates
      from carriage and disease in Nepali children following the planned introduction
      of pneumococcal conjugate vaccines introduction will be essential.

PMID- 24905576
TI  - Usefulness of decrease in oxygen uptake efficiency to identify gas exchange
      abnormality in patients with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Decline in oxygen uptake efficiency (OUE), especially during
      exercise, is found in patients with chronic heart failure. In this study we aimed
      to test the validity and usefulness of OUE in evaluating gas exchange abnormality
      of patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: We
      retrospectively investigated the cardiopulmonary exercise test (CPET) with gas
      exchange measurements in 32 patients with confirmed IPAH. All patients also had
      resting hemodynamic measurements and pulmonary function test (PFT). Sixteen
      healthy subjects, matched by age, sex, and body size were used as controls, also
      had CPET and PFT measurements. RESULTS: In IPAH patients, the magnitude of
      absolute and percentage of predicted (%pred) oxygen uptake efficiency slope
      (OUES) and oxygen uptake efficiency plateau (OUEP), as well as several other CPET
      parameters, were strikingly worse than healthy subjects (P<0.0001). Pattern of
      changes in OUE in patients is similar to that in controls, In IPAH patients, OUE
      values at rest, warming up, anaerobic threshold and peak exercise were all
      significantly lower than in normal (P<0.0001). OUEP%pred, better than OUES%pred,
      correlated significantly with New York Heart Association (NYHA) functional Class
      (r = -0.724, P<0.005), Total Pulmonary Vascular Resistance (TPVR) (r = -0.694,
      P<0.005), diffusing capacity for carbon monoxide (DLCO) (r = 0.577, P<0.05), and
      the lowest ventilation versus CO2 output ratio during exercise (LowestVE/VCO2) (r
      = -0.902, P<0.0001). In addition, the coefficient of variation (COV) of OUEP was
      lower (20.9%) markedly than OUES (34.3%) (P<0.0001). CONCLUSIONS: In patients
      with IPAH, OUES and OUEP are both significantly lower than the healthy subjects.
      OUEP is a better physiological parameter than OUES in evaluating the gas exchange
      abnormality of patients with IPAH.

PMID- 24905577
TI  - Estrogen induces Vav1 expression in human breast cancer cells.
AB  - Vav1, a guanine nucleotide exchange factor (GEF) for Rho family GTPases, is a
      hematopoietic protein involved in a variety of cellular events. In recent years,
      aberrant expression of Vav1 has been reported in non-hematopoietic cancers
      including human breast cancer. It remains to be answered how Vav1 is expressed
      and what Vav1 does in its non-resident tissues. In this study, we aimed to
      explore the mechanism for Vav1 expression in breast cancer cells in correlation
      with estrogen-ER pathway. We not only verified the ectopic expression of Vav1 in
      human breast cancer cell lines, but also observed that Vav1 expression was
      induced by 17beta-estradiol (E2), a typical estrogen receptor (ER) ligand, in ER
      positive cell lines. On the other hand, Tamoxifen, a selective estrogen receptor
      modulator (SERM), and ICI 182,780, an ER antagonist, suppressed the expression of
      Vav1. The estrogen receptor modulating Vav1 expression was identified to be alpha
      form, not beta. Furthermore, treatment of E2 increased the transcription of vav1
      gene by enhancing the promoter activity, though there was no recognizable
      estrogen response element (ERE). Nevertheless, two regions at the vav1 gene
      promoter were defined to be responsible for E2-induced activation of vav1
      promoter. Chromatin immunoprecipitation (ChIP) and co-immunoprecipitation (Co-IP)
      analyses suggested that ERalpha might access to the vav1 promoter via interacting
      with transcription factors, c-Myb and ELF-1. Consequently, the enhanced
      expression of Vav1 led to the elevation of Cyclin D1 and the progression of cell
      cycle. The present study implies that estrogen-ER modulates the transcription and
      expression of Vav1, which may contribute to the proliferation of cancerous cells.

PMID- 24905578
TI  - iPSC-derived neurons from GBA1-associated Parkinson's disease patients show
      autophagic defects and impaired calcium homeostasis.
AB  - Mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the
      lysosomal storage disorder Gaucher's disease (GD), are the strongest genetic risk
      factor for Parkinson's disease (PD) known to date. Here we generate induced
      pluripotent stem cells from subjects with GD and PD harbouring GBA1 mutations,
      and differentiate them into midbrain dopaminergic neurons followed by enrichment
      using fluorescence-activated cell sorting. Neurons show a reduction in
      glucocerebrosidase activity and protein levels, increase in glucosylceramide and
      alpha-synuclein levels as well as autophagic and lysosomal defects. Quantitative
      proteomic profiling reveals an increase of the neuronal calcium-binding protein 2
      (NECAB2) in diseased neurons. Mutant neurons show a dysregulation of calcium
      homeostasis and increased vulnerability to stress responses involving elevation
      of cytosolic calcium. Importantly, correction of the mutations rescues such
      pathological phenotypes. These findings provide evidence for a link between GBA1
      mutations and complex changes in the autophagic/lysosomal system and
      intracellular calcium homeostasis, which underlie vulnerability to
      neurodegeneration. 

PMID- 24905581
TI  - The Influence of the Breast on Physical Activity Participation in Females.
AB  - BACKGROUND: The importance of physical activity is well known. However, previous
      research suggests that breast movement during exercise can be painful,
      embarrassing, and anecdotally deter exercise participation. Therefore, this
      research investigates whether the breast influences physical activity
      participation. METHODS: Female respondents (n = 249) completed a breast health
      and physical activity survey assessing bras and bra fit, physical activity,
      breast pain, comments and improvements, breast history, and demographics.
      RESULTS: Results found that the breast was a barrier to physical activity
      participation for 17% of women. "I can't find the right sports bra" and "I am
      embarrassed by excessive breast movement" were the most influential breast
      related barriers to activity. Breast pain increased with vigorous activity and
      poor breast support. Breast health knowledge increased the use of a sports bra
      and levels of physical activity. CONCLUSIONS: The breast was the fourth greatest
      barrier to physical activity, behind energy/motivation (first), time constraints
      (second), and health (third), despite its omission from previous physical
      activity literature. As 33% of women were not meeting physical activity
      guidelines, increasing breast health knowledge may reduce barriers to physical
      activity.

PMID- 24905582
TI  - Test Equality between Three Treatments under an Incomplete Block Crossover
      Design.
AB  - Under a random effects linear additive risk model, we compare two experimental
      treatments with a placebo in continuous data under an incomplete block crossover
      trial. We develop three test procedures for simultaneously testing equality
      between two experimental treatments and a placebo, as well as interval estimators
      for the mean difference between treatments. We apply Monte Carlo simulations to
      evaluate the performance of these test procedures and interval estimators in a
      variety of situations. We note that the bivariate test procedure accounting for
      the dependence structure based on the F-test is preferable to the other two
      procedures when there is only one of the two experimental treatments has a non
      zero effect vs. the placebo. We note further that when the effects of the two
      experimental treatments vs. a placebo are in the same relative directions and are
      approximately of equal magnitude, the summary test procedure based on a simple
      average of two weighted-least-squares (WLS) estimators can outperform the other
      two procedures with respect to power. When one of the two experimental treatments
      has a relatively large effect vs. the placebo, the univariate test procedure with
      using Bonferroni's equality can be still of use. Finally, we use the data about
      the forced expiratory volume in 1 s (FEV1) readings taken from a double-blind
      crossover trial comparing two different doses of formoterol with a placebo to
      illustrate the use of test procedures and interval estimators proposed here. 

PMID- 24905579
TI  - Clonal analysis of the T-cell response to in vivo expressed Mycobacterium
      tuberculosis protein Rv2034, using a CD154 expression based T-cell cloning
      method.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading
      cause of death worldwide. A better understanding of the role of CD4+ and CD8+ T
      cells, which are both important to TB protection, is essential to unravel the
      mechanisms of protection and to identify the key antigens seen by these T cells.
      We have recently identified a set of in vivo expressed Mtb genes (IVE-TB) which
      is expressed during in vivo pulmonary infection in mice, and shown that their
      encoded antigens are potently recognized by polyclonal T cells from tuberculin
      skin test-positive, in vitro ESAT-6/CFP10-responsive individuals. Here we have
      cloned T cells specific for one of these newly identified in vivo expressed Mtb
      (IVE-TB) antigens, Rv2034. T cells were enriched based on the expression of CD154
      (CD40L), which represents a new method for selecting antigen-specific (low
      frequency) T cells independent of their specific function. An Rv2034-specific
      CD4+ T-cell clone expressed the Th1 markers T-bet, IFN-gamma, TNF-alpha, IL-2 and
      the cytotoxicity related markers granzyme B and CD107a as measured by flow
      cytometry. The clone specifically recognized Rv2034 protein, Rv2034 peptide p81
      100 and Mtb lysate. Remarkably, while the recognition of the dominant p81-100
      epitope was HLA-DR restricted, the T-cell clone also recognized a neighboring
      epitope (p88-107) in an HLA-DR- as well as HLA-DQ1-restricted fashion.
      Importantly, the T-cell clone was able to inhibit Mtb outgrowth from infected
      monocytes significantly. The characterization of the polyfunctional and Mtb
      inhibitory T-cell response to IVE-TB Rv2034 at the clonal level provides detailed
      further insights into the potential of IVE-TB antigens as new vaccine candidate
      antigens in TB. Our new approach allowed the identification of T-cell subsets
      that likely play a significant role in controlling Mtb infection, and can be
      applied to the analysis of T-cell responses in patient populations. 

PMID- 24905584
TI  - Dual-stimuli responsive i-motif/nanoflares for sensing ATP in lysosomes.
AB  - A dual-stimuli responsive i-motif/nanoflare for molecule detection in lysosomes
      was designed. By combining the structure-switchable i-motif sequence and high
      recognition ability of an adenosine triphosphate (ATP) aptamer, subcellular
      sensing and visualization sensing of ATP in lysosomes at the subcellular level
      can be achieved. This general sensing technique can be applied for a broad range
      of cellular communication studies to improve our understanding of subcellular
      signaling and function. 

PMID- 24905583
TI  - beta2-Adrenoceptor involved in smoking-induced airway mucus hypersecretion
      through beta-arrestin-dependent signaling.
AB  - Progression of chronic obstructive pulmonary disease is associated with small
      airway obstruction by accumulation of inflammatory mucous exudates. However, the
      mechanism of mucin hypersecretion after exposure to cigarette smoke (CS) is still
      not clear. In this study, we explored the contribution of beta2-adrenoceptor
      (beta2-AR) signaling to CS extract (CSE)-induced mucus hypersecretion in vitro
      and examined the effect of a beta-blocker on airway mucin hypersecretion in vivo.
      NCI-H292 epithelial cell line was used to determine the contribution of beta2-AR
      signaling to CSE-induced MUC5AC production by treatment with beta2-AR antagonists
      propranolol and ICI118551 and beta2-AR-targeted small interfering RNA. The effect
      of propranolol on airway mucus hypersecretion was examined in a rat model exposed
      to CS. MUC5AC expression was assayed by real-time PCR, immunohistochemistry and
      ELISA. beta2-AR and its downstream signaling were detected by western blot
      analysis. We found that pretreating NCI-H292 cells with propranolol, ICI118551
      for 30 min or beta2AR-targeted siRNA for 48 h reduced MUC5AC mRNA and protein
      levels stimulated by CSE. However,inhibiting the classical beta2AR-cAMP-PKA
      pathway didn't attenuate CSE-induced MUC5AC production, while silencing beta
      arretin2 expression significantly decreased ERK and p38MAPK phosphorylation, thus
      reduced the CSE-stimulated MUC5AC production. In vivo, we found that
      administration of propranolol (25 mg kg(-1) d(-1)) for 28 days significantly
      attenuated the airway goblet cell metaplasia, mucus hypersecretion and MUC5AC
      expression of rats exposed to CS. From the study, beta2-AR-beta-arrestin2-ERK1/2
      signaling was required for CS-induced airway MUC5AC expression. Chronic
      propranolol administration ameliorated airway mucus hypersecretion and MUC5AC
      expression in smoking rats. The exploration of these mechanisms may contribute to
      the optimization of beta2-AR target therapy in chronic obstructive pulmonary
      disease.

PMID- 24905585
TI  - Mercury stable isotope signatures of world coal deposits and historical coal
      combustion emissions.
AB  - Mercury (Hg) emissions from coal combustion contribute approximately half of
      anthropogenic Hg emissions to the atmosphere. With the implementation of the
      first legally binding UNEP treaty aimed at reducing anthropogenic Hg emissions,
      the identification and traceability of Hg emissions from different
      countries/regions are critically important. Here, we present a comprehensive
      world coal Hg stable isotope database including 108 new coal samples from major
      coal-producing deposits in South Africa, China, Europe, India, Indonesia,
      Mongolia, former USSR, and the U.S. A 4.70/00 range in delta(202)Hg (-3.9 to
      0.80/00) and a 10/00 range in Delta(199)Hg (-0.6 to 0.40/00) are observed.
      Fourteen (p < 0.05) to 17 (p < 0.1) of the 28 pairwise comparisons between eight
      global regions are statistically distinguishable on the basis of delta(202)Hg,
      Delta(199)Hg or both, highlighting the potential application of Hg isotope
      signatures to coal Hg emissions tracing. A revised coal combustion Hg isotope
      fractionation model is presented, and suggests that gaseous elemental coal Hg
      emissions are enriched in the heavier Hg isotopes relative to oxidized forms of
      emitted Hg. The model explains to first order the published delta(202)Hg
      observations on near-field Hg deposition from a power plant and global scale
      atmospheric gaseous Hg. Yet, model uncertainties appear too large at present to
      permit straightforward Hg isotope source identification of atmospheric forms of
      Hg. Finally, global historical (1850-2008) coal Hg isotope emission curves were
      modeled and indicate modern-day mean delta(202)Hg and Delta(199)Hg values for
      bulk coal emissions of -1.2 +/- 0.50/00 (1SD) and 0.05 +/- 0.060/00 (1SD). 

PMID- 24905587
TI  - Doubling down: delving into the details of diacid adsorption at aqueous surfaces.
AB  - The behavior of complex interfacial systems is central to an ever-increasing
      number of applications. Vibrational sum frequency (VSF) spectroscopy is a
      powerful technique for obtaining surface specific structural information. The
      coherent nature of VSF that provides surface specificity, however, also creates
      difficulty in spectral interpretation especially as the system complexity
      increases. Computations of VSF spectra shed light on the molecular level source
      of the experimental VSF signal, allowing for the analysis of more complicated
      systems. Unfortunately, the majority of calculations of VSF spectra look at the
      response of the solvent or of rigid molecules and therefore often poorly reflect
      the experimental environment of most VSF spectroscopic measurements. In this
      work, flexible solute molecules at interfaces are investigated by doubling down,
      obtaining and comparing experimental and theoretical spectra, to determine a more
      accurate computational treatment. The surface behavior and VSF spectra of
      glutaric acid and adipic acid at the air/water interface are determined
      experimentally and calculated using a combination of classical molecular dynamics
      and density functional theory. Both diacids are found to be surface active. At
      high concentrations, glutaric acid forms dimers altering its VSF response and
      acidic properties. Calculated VSF spectra are found to be sensitive to
      vibrational mode frequencies, with ordering and spacing affecting relative
      intensities, as well as molecular conformation. A proper description requires
      consideration of multiple conformers and anharmonic effects on the molecular
      vibrational energies. 

PMID- 24905586
TI  - Kinetics and prediction of HBsAg loss during long-term therapy with nucleos(t)ide
      analogues of different potency in patients with chronic hepatitis B.
AB  - BACKGROUND & AIMS: About 350-400 million people are infected with hepatitis B
      virus (HBV) chronically and 1 million people die of hepatitis B virus (HBV)
      related liver diseases. Nucleos(t)ide analogues (NAs) have been used for the
      treatment against HBV. However, few studies have investigated the long-term
      effects of different nucleos(t)ide analogues on levels of hepatitis B surface
      antigen (HBsAg) in patients with chronic hepatitis B (CHB). The aims of this
      study were to measure the magnitude of HBsAg reduction by long-term monotherapy
      with adefovir dipivoxil (ADV) and entecavir (ETV), to compare HBsAg reduction
      between the two drugs of different potency and to predict the expected time
      needed to achieve HBsAg loss. METHODS: We retrospectively evaluated the kinetics
      of HBsAg in 67 patients with CHB who all exhibited persistent viral suppression.
      These patients were treated with ADV or ETV for at least 6 years. HBV genotype
      was determined at baseline. Liver biochemistry, HBV serological markers, serum
      HBV DNA and HBsAg titers were determined at baseline, half year and yearly from
      year 1 to 6. RESULTS: Serum HBsAg titers after treatment with ADV or ETV were
      significantly lower than the baseline titers (P<0.05). HBsAg reduction rate of
      patients treated with ETV (0.11 log10 IU/mL/ year) was higher than that treated
      with ADV (0.10 log10 IU/mL/year), and the calculated expected time to HBsAg loss
      for patients treated with ETV (approximate 24.99 years) was shorter than that
      with ADV (approximate 30.33 years), but there was no statistically significant
      difference between two groups (P>0.05). CONCLUSION: Serum HBsAg titers gradually
      decreased during long-term treatment with either ADV or ETV. It appears that the
      potency of ADV on HBsAg reduction is close to that of ETV, as long as patients
      have achieved persistent viral suppression.

PMID- 24905588
TI  - In silico models to predict dermal absorption from complex agrochemical
      formulations.
AB  - Dermal absorption is a critical part in the risk assessment of complex mixtures
      such as agrochemical formulations. To reduce the number of in vivo or in vitro
      absorption experiments, the present study aimed to develop an in silico
      prediction model that considers mixture-related effects. Therefore, an
      experimental 'real-world' dataset derived from regulatory in vitro studies with
      human and rat skin was processed. Overall, 56 test substances applied in more
      than 150 mixtures were used. Descriptors for the substances as well as the
      mixtures were generated and used for multiple linear regression analysis.
      Considering the heterogeneity of the underlying data set, the final model
      provides a good fit (r2 = 0.75) and is able to estimate the influence of a newly
      composed formulation on dermal absorption of a well-known substance (predictivity
      Q2Ext = 0.73). Application of this model would reduce animal and non-animal
      testings when used for the optimization of formulations in early developmental
      stages, or would simplify the registration process, if accepted for read-across. 

PMID- 24905589
TI  - Clinical impact of de-regulated Notch-1 and Notch-3 in the development and
      progression of HPV-associated different histological subtypes of precancerous and
      cancerous lesions of human uterine cervix.
AB  - BACKGROUND: Cervical cancer is the leading cause of cancer related deaths among
      women in India. Limited reports are available for Notch-1 and Notch-3 protein in
      cervical carcinoma, which play crucial role in cell proliferation,
      differentiation, and apoptosis. METHODS: This study was designed to evaluate the
      role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma.
      A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98),
      precancer (n = 30) and non-neoplastic cervical tissues (n = 40) were screened for
      HPV infection by PCR and expression of Notch-1 and Notch-3 protein by
      Immunohistochemistry and Immunoblotting. RESULTS: 80% (24/30) were found to be
      positive for HPV in precancer and 86.7% (85/98) in cancer patients. Notch-1
      expression of precancer and cancer cases was found to be significantly down
      regulated with severity of disease in nuclear (3.43+/-0.29; 2.04+/-0.19, p =
      0.0001, p = 0.0001) and cytoplasm (3.07+/-0.29; 2.29+/-0.17, p = 0.0001, p =
      0.0001) obtained from different stages as compared to normal cervix tissue
      (5.40+/-0.19, 4.97+/-0.15; p<0.001; p<0.001). However, Notch-3 expression of
      above cases was significantly up-regulated with severity of disease and showed
      intense nuclear (4.17+/-0.39; 4.74+/-0.18, p = 0.0001, p = 0.0001) and cytoplasm
      (3.67+/-0.36; 4.48+/-0.18, p = 0.0001, p = 0.0001) of different stages as
      compared to normal cervix tissue (0.95+/-0.20, 0.70+/-0.20; p<0.001; p<0.001)
      respectively. CONCLUSIONS: These findings suggest that Notch-1 and Notch-3 may
      play an important role with synergistic effect of HPV in regulating development
      and proliferation of cervical cancer through the deregulation of Notch
      signalling. This study also shows the clinical utility of both proteins which may
      be used as predictable biomarkers in diagnosing different histological sub-types
      of HPV associated cervical cancer. Nevertheless, abnormal activation of this
      pathway may provide legitimate targets for cervical cancer therapy.

PMID- 24905590
TI  - A longitudinal study on dual-tasking effects on gait: cognitive change predicts
      gait variance in the elderly.
AB  - Neuropsychological abilities have found to explain a large proportion of variance
      in objective measures of walking gait that predict both dementia and falling
      within the elderly. However, to this date there has been little research on the
      interplay between changes in these neuropsychological processes and walking gait
      overtime. To our knowledge, the present study is the first to investigate intra
      individual changes in neurocognitive test performance and gait step time at two
      time points across a one-year span. Neuropsychological test scores from 440
      elderly individuals deemed cognitively normal at Year One were analyzed via
      repeated measures t-tests to assess for decline in cognitive performance at Year
      Two. 34 of these 440 individuals neuropsychological test performance
      significantly declined at Year Two; whereas the "non-decliners" displayed
      improved memory, working memory, attention/processing speed test performance.
      Neuropsychological test scores were also submitted to factor analysis at both
      time points for data reduction purposes and to assess the factor stability
      overtime. Results at Year One yielded a three-factor solution: Language/Memory,
      Executive Attention/Processing Speed, and Working Memory. Year Two's test scores
      also generated a three-factor solution (Working Memory, Language/Executive
      Attention/Processing Speed, and Memory). Notably, language measures loaded on
      Executive Attention/Processing Speed rather than on the Memory factor at Year
      Two. Hierarchal multiple regression revealed that both Executive
      Attention/Processing Speed and sex significantly predicted variance in dual task
      step time at both time points. Remarkably, in the "decliners", the magnitude of
      the contribution of the neuropsychological characteristics to gait variance
      significantly increased at Year Two. In summary, this study provides longitudinal
      evidence of the dynamic relationship between intra-individual cognitive change
      and its influence on dual task gait step time. These results also indicate that
      the failure to show improved test performance (particularly, on memory tests)
      with repeated administrations might prove to be useful of indicator of early
      cognitive decline. 

PMID- 24905591
TI  - Francois Jacob, or the thirst for novelty.
AB  - Francois Jacob tackled embryonic development from 1972 onwards, in the "Genetique
      cellulaire" Unit of the Molecular Biology Department at the Pasteur Institute,
      taking as models teratocarcinoma and the early stages of mouse embryo
      development. Studies on teratocarcinoma provided no major information about
      developmental processes, but they were the essential step without which embryonic
      stem cells (ES, iPS) would probably not have been discovered. The mechanisms of
      development were revealed by genetic approaches coupled to molecular biology, but
      with the Drosophila model rather than the mouse embryo. Since these studies, it
      has been revealed that developmental mechanisms among animals have proven to be
      universal. None of these results were predicted in 1972. 

PMID- 24905592
TI  - From stress to psychosis: whom, how, when and why?
AB  - The role of stress in precipitating the onset and relapse of psychosis has been
      now widely recognised. Over the past decade, the major challenge of research in
      this field has been to elucidate the biological mechanisms involved in the
      interaction between stress and psychosis onset. Obvious focus of this research
      has been the study of biological systems involved in the stress response. I will
      here briefly discuss the current evidence of abnormalities in stress biomarkers,
      such as cortisol and inflammatory markers, in patients with psychosis and their
      possible clinical implications. Stress biomarkers appear to hold strong potential
      as predictors of psychosis as well as of clinical outcome, and may represent
      optimal targets for the development of novel therapeutic agents for psychosis. 

PMID- 24905593
TI  - Jointly Modeling Event Time and Skewed-Longitudinal Data with Missing Response
      and Mismeasured Covariate for AIDS Studies.
AB  - In longitudinal studies it is often of interest to investigate how a repeatedly
      measured marker in time is associated with a time to an event of interest. This
      type of research question has given rise to a rapidly developing field of
      biostatistics research that deals with the joint modeling of longitudinal and
      time-to-event data. Normality of model errors in longitudinal model is a routine
      assumption, but it may be unrealistically obscuring important features of subject
      variations. Covariates are usually introduced in the models to partially explain
      between- and within-subject variations, but some covariates such as CD4 cell
      count may be often measured with substantial errors. Moreover, the responses may
      encounter nonignorable missing. Statistical analysis may be complicated
      dramatically based on longitudinal-survival joint models where longitudinal data
      with skewness, missing values, and measurement errors are observed. In this
      article, we relax the distributional assumptions for the longitudinal models
      using skewed (parametric) distribution and unspecified (nonparametric)
      distribution placed by a Dirichlet process prior, and address the simultaneous
      influence of skewness, missingness, covariate measurement error, and time-to
      event process by jointly modeling three components (response process with missing
      values, covariate process with measurement errors, and time-to-event process)
      linked through the random-effects that characterize the underlying individual
      specific longitudinal processes in Bayesian analysis. The method is illustrated
      with an AIDS study by jointly modeling HIV/CD4 dynamics and time to viral rebound
      in comparison with potential models with various scenarios and different
      distributional specifications. 

PMID- 24905594
TI  - Coding and transformations in the olfactory system.
AB  - How is sensory information represented in the brain? A long-standing debate in
      neural coding is whether and how timing of spikes conveys information to
      downstream neurons. Although we know that neurons in the olfactory bulb (OB)
      exhibit rich temporal dynamics, the functional relevance of temporal coding
      remains hotly debated. Recent recording experiments in awake behaving animals
      have elucidated highly organized temporal structures of activity in the OB. In
      addition, the analysis of neural circuits in the piriform cortex (PC)
      demonstrated the importance of not only OB afferent inputs but also intrinsic PC
      neural circuits in shaping odor responses. Furthermore, new experiments involving
      stimulation of the OB with specific temporal patterns allowed for testing the
      relevance of temporal codes. Together, these studies suggest that the relative
      timing of neuronal activity in the OB conveys odor information and that neural
      circuits in the PC possess various mechanisms to decode temporal patterns of OB
      input. 

PMID- 24905595
TI  - The neurobiology of language beyond single words.
AB  - A hallmark of human language is that we combine lexical building blocks retrieved
      from memory in endless new ways. This combinatorial aspect of language is
      referred to as unification. Here we focus on the neurobiological infrastructure
      for syntactic and semantic unification. Unification is characterized by a high
      speed temporal profile including both prediction and integration of retrieved
      lexical elements. A meta-analysis of numerous neuroimaging studies reveals a
      clear dorsal/ventral gradient in both left inferior frontal cortex and left
      posterior temporal cortex, with dorsal foci for syntactic processing and ventral
      foci for semantic processing. In addition to core areas for unification, further
      networks need to be recruited to realize language-driven communication to its
      full extent. One example is the theory of mind network, which allows listeners
      and readers to infer the intended message (speaker meaning) from the coded
      meaning of the linguistic utterance. This indicates that sensorimotor simulation
      cannot handle all of language processing. 

PMID- 24905597
TI  - Emotion and decision making: multiple modulatory neural circuits.
AB  - Although the prevalent view of emotion and decision making is derived from the
      notion that there are dual systems of emotion and reason, a modulatory
      relationship more accurately reflects the current research in affective
      neuroscience and neuroeconomics. Studies show two potential mechanisms for
      affect's modulation of the computation of subjective value and decisions.
      Incidental affective states may carry over to the assessment of subjective value
      and the decision, and emotional reactions to the choice may be incorporated into
      the value calculation. In addition, this modulatory relationship is reciprocal:
      Changing emotion can change choices. This research suggests that the neural
      mechanisms mediating the relation between affect and choice vary depending on
      which affective component is engaged and which decision variables are assessed.
      We suggest that a detailed and nuanced understanding of emotion and decision
      making requires characterizing the multiple modulatory neural circuits underlying
      the different means by which emotion and affect can influence choices. 

PMID- 24905599
TI  - The purifying trend in the chromosomal integron in Vibrio cholerae strains during
      the seventh pandemic.
AB  - Chromosomal integron (CI) arrays in Vibrio spp. are generally large and display
      great variation. Here we determined the sequence of CI array in a toxigenic O139
      Vibriocholerae strain and compared it with the arrays from the genome of
      different O1 biotypes available in GenBank. Then PCR scanning was used to
      determine the CI array variations in 83 epidemic O139 strains and subsequently
      these variations were compared with that found in toxigenic O1 El Tor strains in
      our previous work. Few differences were observed in the cohort of toxigenic O139
      strains compared to the toxigenic O1 El Tor strains. On the basis of CI arrays,
      the toxigenic O1 El Tor and O139 strains isolated concurrently in recent years
      appear to be more similar to each other than to the O1 strains isolated in
      previous decades, suggesting a closer evolutionary relationship between them.
      Comparison of CI arrays in toxigenic O1 El Tor and O139 V. cholerae strains
      isolated between 1961 and 2009 revealed a purifying trend in the CI arrays in the
      chronological order during the seventh pandemic. 

PMID- 24905596
TI  - Functions and dysfunctions of adult hippocampal neurogenesis.
AB  - Adult neurogenesis, a developmental process of generating functionally integrated
      neurons, occurs throughout life in the hippocampus of the mammalian brain and
      showcases the highly plastic nature of the mature central nervous system.
      Significant progress has been made in recent years to decipher how adult
      neurogenesis contributes to brain functions. Here we review recent findings that
      inform our understanding of adult hippocampal neurogenesis processes and special
      properties of adult-born neurons. We further discuss potential roles of adult
      born neurons at the circuitry and behavioral levels in cognitive and affective
      functions and how their dysfunction may contribute to various brain disorders. We
      end by considering a general model proposing that adult neurogenesis is not a
      cell-replacement mechanism, but instead maintains a plastic hippocampal neuronal
      circuit via the continuous addition of immature, new neurons with unique
      properties and structural plasticity of mature neurons induced by new-neuron
      integration. 

PMID- 24905600
TI  - Genetic variations of live attenuated plague vaccine strains (Yersinia pestis
      EV76 lineage) during laboratory passages in different countries.
AB  - Plague, one of the most devastating infectious diseases in human history, is
      caused by the bacterial species Yersinia pestis. A live attenuated Y. pestis
      strain (EV76) has been widely used as a plague vaccine in various countries
      around the world. Here we compared the whole genome sequence of an EV76 strain
      used in China (EV76-CN) with the genomes of Y. pestis wild isolates to identify
      genetic variations specific to the EV76 lineage. We identified 6 SNPs and 6
      Indels (insertions and deletions) differentiating EV76-CN from its counterparts.
      Then, we screened these polymorphic sites in 28 other strains of EV76 lineage
      that were stored in different countries. Based on the profiles of SNPs and
      Indels, we reconstructed the parsimonious dissemination history of EV76 lineage.
      This analysis revealed that there have been at least three independent imports of
      EV76 strains into China. Additionally, we observed that the pyrE gene is a
      mutation hotspot in EV76 lineages. The fine comparison results based on whole
      genome sequence in this study provide better understanding of the effects of
      laboratory passages on the accumulation of genetic polymorphisms in plague
      vaccine strains. These variations identified here will also be helpful in
      discriminating different EV76 derivatives. 

PMID- 24905601
TI  - Microfluidic in-reservoir pre-concentration using a buffer drain technique.
AB  - Pre-concentration methods are essential for detecting low concentrations of
      influenza virus in biological samples from patients. Here, we describe a new
      method for draining buffer from solution in the reservoir of a microfluidic
      device to increase the concentration of virus in the reservoir. Viruses were
      captured in the reservoir by an ion depletion barrier from connected ion
      selective microfluidic channels. 75 MUl of buffer was successfully drained from a
      100 MUl sample, resulting in a 4-fold increase in influenza hemagglutinin
      concentration in the reservoir. The volume of the final concentrated sample was
      suitable for detection of influenza hemagglutinin by the enzyme-linked
      immunosorbent assay, demonstrating the usefulness of the developed platform for
      enhanced sensitivity of virus detection in a conventional analysis. 

PMID- 24905602
TI  - Spindle microtubule dysfunction and cancer predisposition.
AB  - Chromosome segregation and spindle microtubule dynamics are strictly coordinated
      during cell division in order to preserve genomic integrity. Alterations in the
      genome that affect microtubule stability and spindle assembly during mitosis may
      contribute to genomic instability and cancer predisposition, but directly testing
      this potential link poses a significant challenge. Germ-line mutations in tumor
      suppressor genes that predispose patients to cancer and alter spindle microtubule
      dynamics offer unique opportunities to investigate the relationship between
      spindle dysfunction and carcinogenesis. Mutations in two such tumor suppressors,
      adenomatous polyposis coli (APC) and Shwachman-Bodian-Diamond syndrome (SBDS),
      affect multifunctional proteins that have been well characterized for their roles
      in Wnt signaling and interphase ribosome assembly, respectively. Less understood,
      however, is how their shared involvement in stabilizing the microtubules that
      comprise the mitotic spindle contributes to cancer predisposition. Here, we
      briefly discuss the potential for mutations in APC and SBDS as informative tools
      for studying the impact of mitotic spindle dysfunction on cellular
      transformation.

PMID- 24905604
TI  - Fabrication of implantable, enzyme-immobilized glutamate sensors for the
      monitoring of glutamate concentration changes in vitro and in vivo.
AB  - Glutamate sensors based on the immobilization of glutamate oxidase (GlutOx) were
      prepared by adsorption on electrodeposited chitosan (Method 1) and by
      crosslinking with glutaraldehyde (Method 2) on micromachined platinum
      microelectrodes. It was observed that glutamate sensors prepared by Method 1 have
      faster response time (<2 s) and lower detection limit (2.5+/-1.1 MUM) compared to
      that prepared by Method 2 (response time: <5 sec and detection limit: 6.5+/-1.7
      MUM); glutamate sensors prepared by Method 2 have a larger linear detection range
      (20-352 MUM) and higher sensitivity (86.8+/-8.8 nA.MUM-1.cm-2, N=12) compared to
      those prepared by Method 1 (linear detection range: 20-217 MUM and sensitivity:
      34.9+/-4.8 nA.MUM-1.cm-2, N=8). The applicability of the glutamate sensors in
      vivo was also demonstrated. The glutamate sensors were implanted into the rat
      brain to monitor the stress-induced extracellular glutamate release in the
      hypothalamus of the awake, freely moving rat.

PMID- 24905603
TI  - Resveratrol and calcium signaling: molecular mechanisms and clinical relevance.
AB  - Resveratrol is a naturally occurring compound contributing to cellular defense
      mechanisms in plants. Its use as a nutritional component and/or supplement in a
      number of diseases, disorders, and syndromes such as chronic diseases of the
      central nervous system, cancer, inflammatory diseases, diabetes, and
      cardiovascular diseases has prompted great interest in the underlying molecular
      mechanisms of action. The present review focuses on resveratrol, specifically its
      isomer trans-resveratrol, and its effects on intracellular calcium signaling
      mechanisms. As resveratrol's mechanisms of action are likely pleiotropic, its
      effects and interactions with key signaling proteins controlling cellular calcium
      homeostasis are reviewed and discussed. The clinical relevance of resveratrol's
      actions on excitable cells, transformed or cancer cells, immune cells and retinal
      pigment epithelial cells are contrasted with a review of the molecular mechanisms
      affecting calcium signaling proteins on the plasma membrane, cytoplasm,
      endoplasmic reticulum, and mitochondria. The present review emphasizes the
      correlation between molecular mechanisms of action that have recently been
      identified for resveratrol and their clinical implications. 

PMID- 24905605
TI  - Oligo-carrageenan kappa-induced reducing redox status and increase in TRR/TRX
      activities promote activation and reprogramming of terpenoid metabolism in
      Eucalyptus trees.
AB  - In order to analyze whether the reducing redox status and activation of
      thioredoxin reductase (TRR)/thioredoxin(TRX) system induced by oligo-carrageenan
      (OC) kappa in Eucalyptus globulus activate secondary metabolism increasing
      terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa,
      or with inhibitors of NAD(P)H, ascorbate (ASC) and (GSH) synthesis and TRR
      activity, CHS-828, lycorine, buthionine sulfoximine (BSO) and auranofine,
      respectively, and with OC kappa and cultivated for four months. The main
      terpenoids in control Eucalyptus trees were eucalyptol (76%), alpha-pinene
      (7.4%), aromadendrene (3.6%), silvestrene (2.8%), sabinene (2%) and alpha
      terpineol (0.9%). Treated trees showed a 22% increase in total essential oils as
      well as a decrease in eucalyptol (65%) and sabinene (0.8%) and an increase in
      aromadendrene (5%), silvestrene (7.8%) and other ten terpenoids. In addition,
      treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to
      carene, alpha-terpinene, alpha-fenchene, gamma-maaliene, spathulenol and alpha
      camphenolic aldehyde. Most increased and de novo synthesized terpenoids have
      potential insecticidal and antimicrobial activities. Trees treated with CHS-828,
      lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased
      and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status
      and activation of TRR/TRX system enhance secondary metabolism increasing the
      synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus
      trees. 

PMID- 24905607
TI  - Molecular classification of pesticides including persistent organic pollutants,
      phenylurea and sulphonylurea herbicides.
AB  - Pesticide residues in wine were analyzed by liquid chromatography-tandem mass
      spectrometry. Retentions are modelled by structure-property relationships.
      Bioplastic evolution is an evolutionary perspective conjugating effect of
      acquired characters and evolutionary indeterminacy-morphological determination
      natural selection principles; its application to design co-ordination index
      barely improves correlations. Fractal dimensions and partition coefficient
      differentiate pesticides. Classification algorithms are based on information
      entropy and its production. Pesticides allow a structural classification by
      nonplanarity, and number of O, S, N and Cl atoms and cycles; different behaviours
      depend on number of cycles. The novelty of the approach is that the structural
      parameters are related to retentions. Classification algorithms are based on
      information entropy. When applying procedures to moderate-sized sets, excessive
      results appear compatible with data suffering a combinatorial explosion. However,
      equipartition conjecture selects criterion resulting from classification between
      hierarchical trees. Information entropy permits classifying compounds agreeing
      with principal component analyses. Periodic classification shows that pesticides
      in the same group present similar properties; those also in equal period, maximum
      resemblance. The advantage of the classification is to predict the retentions for
      molecules not included in the categorization. Classification extends to
      phenyl/sulphonylureas and the application will be to predict their retentions. 

PMID- 24905606
TI  - The fruits of wampee inhibit H2O2-induced apoptosis in PC12 cells via the NF
      kappaB pathway and regulation of cellular redox status.
AB  - Wampee (Clausena lansium) fruits (CLS), whose pulp can be used to prepare fruit
      cups, desserts, jam, or jelly, can be eaten along with the peel. In this study, a
      PC12 cell model was built to observe the protective effect of CLS against H2O2
      induced oxidative stress. We found that pretreatment with CLS increased cell
      viability and inhibited cytotoxicity, caspase-3 activity and DNA condensation.
      CLS also attenuated the increase in ROS production and MMP reduction. Moreover,
      we attempted to determine whether CLS suppressed the expression and
      phosphorylation of NF-kappaB. Western blot and immunostaining assay revealed that
      CLS inhibited H2O2-induced up-regulation of NF-kappaB p65 and pNF-kappaB p65. And
      CLS significantly suppressed the translocation of NF-kappaB p65 and pNF-kappaB
      p65 from cytoplasm to nuclear. Also, seven major compounds including a new
      flavanoid, luteolin-4'-O-beta-d-gluco-pyranoside (3) and six known compounds 1,2,
      4-7 were isolated and identified from CLS. Their antioxidative and H2O2-induced
      PC12 cell apoptosis-reversing activity were determined. These findings suggest
      that CLS and its major constituents (flavanoids) may be potential antioxidant
      agents and should encourage further research into their use as a functional food
      for neurodegenerative diseases. 

PMID- 24905608
TI  - Drug-induced conformational population shifts in topoisomerase-DNA ternary
      complexes.
AB  - Type II topoisomerases (TOP2) are enzymes that resolve the topological problems
      during DNA replication and transcription by transiently cleaving both strands and
      forming a cleavage complex with the DNA. Several prominent anti-cancer agents
      inhibit TOP2 by stabilizing the cleavage complex and engendering permanent DNA
      breakage. To discriminate drug binding modes in TOP2-alpha and TOP2-beta, we
      applied our newly developed scoring function, dubbed AutoDock4RAP, to evaluate
      the binding modes of VP-16, m-AMSA, and mitoxantrone to the cleavage complexes.
      Docking reproduced crystallographic binding mode of VP-16 in a ternary complex of
      TOP2-beta with root-mean-square deviation of 0.65 A. Molecular dynamics
      simulation of the complex confirmed the crystallographic binding mode of VP-16
      and the conformation of the residue R503. Drug-related conformational changes in
      R503 have been observed in ternary complexes with m-AMSA and mitoxantrone.
      However, the R503 rotamers in these two simulations deviate from their
      crystallographic conformations, indicating a relaxation dynamics from the
      conformations determined with the drug replacement procedure. The binding mode of
      VP-16 in the cleavage complex of TOP2-alpha was determined by the conjoint use of
      docking and molecular dynamics simulations, which fell within a similar binding
      pocket of TOP2-beta cleavage complex. Our findings may facilitate more efficient
      design efforts targeting TOP2-alpha specific drugs. 

PMID- 24905609
TI  - EAACI food allergy and anaphylaxis guidelines: managing patients with food
      allergy in the community.
AB  - The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and
      Anaphylaxis Guidelines, managing patients with food allergy (FA) in the
      community, intend to provide guidance to reduce the risk of accidental allergic
      reactions to foods in the community. This document is intended to meet the needs
      of early-childhood and school settings as well as providers of non-prepackaged
      food (e.g., restaurants, bakeries, takeaway, deli counters, and fast-food
      outlets) and targets the audience of individuals with FA, their families, patient
      organizations, the general public, policymakers, and allergists. Food allergy is
      the most common trigger of anaphylaxis in the community. Providing children and
      caregivers with comprehensive information on food allergen avoidance and prompt
      recognition and management of allergic reactions are of the utmost importance.
      Provision of adrenaline auto-injector devices and education on how and when to
      use these are essential components of a comprehensive management plan. Managing
      patients at risk of anaphylaxis raises many challenges, which are specific to the
      community. This includes the need to interact with third parties providing food
      (e.g., school teachers and restaurant staff) to avoid accidental exposure and to
      help individuals with FA to make safe and appropriate food choices. Education of
      individuals at risk and their families, their peers, school nurses and teachers
      as well as restaurant and other food retail staff can reduce the risk of
      severe/fatal reactions. Increased awareness among policymakers may improve
      decision-making on legislation at local and national level. 

PMID- 24905610
TI  - Saddle fit and management: An investigation of the association with equine
      thoracolumbar asymmetries, horse and rider health.
AB  - REASONS FOR PERFORMING STUDY: No previous studies have investigated
      interrelationships between saddle fit/management, equine thoracolumbar
      asymmetries, rider and horse health. OBJECTIVES: To assess associations between
      data obtained by clinical assessment and those provided by riders via a
      questionnaire. STUDY DESIGN: Clinical assessment of a convenience sample of
      horses and riders compared with a Web-based questionnaire survey (n = 205).
      METHODS: Horse thoracolumbar asymmetries at predetermined sites, the presence of
      lameness (in hand and/or ridden), saddle slip, saddle fit/management and rider
      straightness were assessed. Kappa statistics were used to assess the relationship
      between categorical clinical data and questionnaire data from riders. Spearman's
      correlation was used to investigate associations between outcomes from clinical
      assessment (horse, saddle and rider data) and information provided by riders.
      RESULTS: There was a 40.5% (205 of 506) questionnaire response rate. Thirty
      horses (14.6%) had saddle slip, which was significantly associated with hindlimb
      lameness or gait abnormalities (P<0.001), but only 2 riders had considered a link
      between saddle slip and lameness. Rider back pain was common (38.5%) and
      associated with ill-fitting saddles (P = 0.03) and either a quadrupedally reduced
      cranial phase of the step or a stiff, stilted canter (P = 0.006). Well-fitted
      saddles were associated with frequent saddle fit checks (P = 0.004). Minor
      thoracolumbar asymmetries (P = 0.04) were negatively associated with ill-fitting
      saddles and positively associated with rider skill level (P = 0.001).
      CONCLUSIONS: The interaction between the horse, saddle and rider is complex. Ill
      fitting saddles and a stiff, stilted canter or quadrupedally reduced cranial
      phase of the step are associated with rider back pain. Equine back pain and minor
      thoracolumbar asymmetries are associated with ill-fitting saddles. Saddle fit
      should be checked more often than once yearly to lower the number of ill-fitting
      saddles. Riders, trainers and other professionals involved in equine care and
      performance need better education to recognise ill-fitting saddles, lameness,
      saddle slip and rider crookedness.

PMID- 24905611
TI  - Intraoperative frozen section risk assessment accurately tailors the surgical
      staging in patients affected by early-stage endometrial cancer: the application
      of 2 different risk algorithms.
AB  - OBJECTIVE: The aim of this study was to investigate the frozen section (FS)
      accuracy in tailoring the surgical staging of patients affected by endometrial
      cancer, using 2 different risk classifications. METHODS/MATERIALS: A
      retrospective analysis of 331 women affected by type I endometrial cancer and
      submitted to FS assessment at the time of surgery. Pathologic features were
      examined on the frozen and permanent sections according to both the GOG33 and the
      Mayo Clinic algorithms. We compared the 2 models through the determination of
      Landis and Koch kappa statistics, concordance rate, sensitivity, specificity,
      positive predictive value, and negative predictive value for each risk algorithm,
      to assess whether there are differences in FS accuracy depending on the model
      used. RESULTS: The observed agreement between the frozen and permanent sections
      was respectively good (k = 0.790) for the GOG33 and optimal (k = 0.810) for the
      Mayo classification. Applying the GOG33 algorithm, 20 patients (6.7%) were moved
      to an upper risk status, and 20 (6.7%) were moved to a lower risk status on the
      permanent section; the concordance rate was 86.5%. With the Mayo Clinic
      algorithm, discordant cases between frozen and permanent sections were 19 (7.6%),
      and the risk of lymphatic spread was underestimated only in 1 case (0.4%); the
      concordance rate was 92.4%. The sensitivity, specificity, positive predictive
      value, and negative predictive value for the GOG33 were 92%, 94%, 92%, and 93%,
      whereas with the Mayo algorithm, these were 98%, 91%, 77%, and 99%, respectively.
      CONCLUSIONS: According to higher correlation rate and observed agreement (92.4%
      vs 86.5% and k = 0.810 vs 0.790, respectively), the Mayo Clinic algorithm
      minimizes the number of patients undertreated at the time of surgery than the
      GOG33 classification and can be adopted as an FS algorithm to tailor the surgical
      treatment of early-stage endometrial cancer even in different centers.

PMID- 24905612
TI  - Recurrence patterns of advanced ovarian, fallopian tube, and peritoneal cancers
      after complete cytoreduction during interval debulking surgery.
AB  - OBJECTIVES: Similar to primary debulking surgery, complete resection of all
      macroscopic diseases during interval debulking surgery (IDS) is the primary
      objective while using neoadjuvant chemotherapy followed by IDS for advanced
      ovarian, fallopian tube, and peritoneal cancers. However, most patients develop
      recurrent disease even after complete cytoreduction during IDS. This study aims
      to identify recurrence patterns of the ovarian, fallopian tube, and peritoneal
      cancers in patients who underwent complete cytoreduction during IDS. METHODS: We
      retrospectively reviewed data of patients with stage III or IV ovarian, fallopian
      tube, and peritoneal cancers who were treated at our hospital from January 1,
      2005, to December 31, 2011. RESULTS: In this study, 105 patients underwent
      neoadjuvant chemotherapy followed by IDS and achieved complete cytoreduction. The
      median follow-up period was 42.1 months. Recurrence was documented in 70 patients
      (66.7%), and 35 (33.3%) showed no evidence of disease. Peritoneal dissemination
      was the most common recurrence (60.0%) observed. In multivariate analysis,
      positive peritoneal cytology (P = 0.0003) and elevated pre-IDS serum CA125 levels
      (P = 0.046) were independent risk factors for recurrence. CONCLUSIONS: After
      complete cytoreduction during IDS in patients with stage III or IV ovarian,
      fallopian tube, and peritoneal cancers, positive peritoneal cytology at IDS and
      elevated pre-IDS CA125 levels are associated with an increased risk of cancer
      recurrence. Positive peritoneal cytology during IDS is a particularly strong
      predictive factor for poor outcomes in these patients.

PMID- 24905613
TI  - Venous thromboembolism in advanced ovarian cancer patients undergoing frontline
      adjuvant chemotherapy.
AB  - OBJECTIVE: The aim of this study was to define the incidence and prognostic
      significance of venous thromboembolism (VTE) in patients with advanced,
      epithelial ovarian cancer undergoing frontline adjuvant chemotherapy after an
      extended period (28 days) of postoperative prophylaxis. METHODS: A retrospective
      analysis of patients with advanced, epithelial ovarian cancer who underwent
      surgery and chemotherapy at a single institution from January 2008 through
      December 2011 was performed. Exclusion criteria were history of VTE, VTE during
      the postoperative period, clear cell histology, use of anticoagulation for a
      different indication, and lack of compliance with 28 days of postoperative
      prophylaxis with a low-molecular-weight heparin. Baseline patient demographics
      and oncologic outcomes were analyzed. Clinically symptomatic VTE was identified
      and confirmed with imaging studies. Otherwise, VTE was identified on imaging
      studies done to assess disease status at the conclusion of adjuvant chemotherapy.
      RESULTS: One hundred twenty-eight patients met criteria for inclusion. Sixteen
      patients had a reported VTE during the time they were on frontline chemotherapy
      (12.5%). Nine patients (7%) had a pulmonary embolus, and 8 (6.3%) had a deep vein
      thrombus. The mean BMI in the group that developed VTE was 28, and in the group
      without VTE, it was 26.5 (P = 0.23). Three (23%) of the 16 patients who developed
      VTE had undergone a suboptimal cytoreduction compared with 12 (11%) of the 112 in
      the group with no VTE (P = 0.4). Six (37%) of the 16 patients who developed VTE
      during chemotherapy underwent a bowel resection and/or splenectomy during their
      cytoreductive surgery compared with 18 (16%) of the 112 patients who did not
      develop VTE (P = 0.079). Eight of the patients in the VTE group had indwelling
      venous catheters during chemotherapy (50%) compared with 39 (35%) in the group
      with no VTE (P = 0.27). In the group that developed VTE, there was a trend toward
      increased preoperative CA-125, higher rates of bowel resection and/or splenectomy
      during surgery, decreased use of aspirin, and inferior survival. On multivariate
      analysis, patients who developed VTE had significantly longer postoperative
      hospital stays (7 vs 5 days [P = 0.009]) and lower rates of complete response (P
      = 0.01). CONCLUSIONS: A 12.5% risk for VTE merits consideration of prophylaxis
      during chemotherapy in this cohort. A randomized, controlled trial is needed to
      clarify whether the benefits of long-term prophylaxis outweigh the risks and
      costs of such therapy.

PMID- 24905614
TI  - Femoral nerve injury complicating surgery for gynecologic cancer.
AB  - OBJECTIVE: The aim of this study was to report the incidence, severity, and
      factors associated with femoral nerve injury during gynecologic cancer surgery.
      METHODS: All patients who underwent abdominal surgery for gynecologic cancer
      entered the study. A retrospective review of the medical records was carried out
      for patients operated on from 2003 to April 2011. After this analysis, the use of
      the Bookwalter retractor was modified and the data were prospectively recorded.
      RESULTS: In the first period, femoral nerve injury was observed in 11 (2.7%) of
      406 patients, occurring with a significantly higher frequency when the Bookwalter
      retractor was used (5.1% vs 0%, P < 0.01) and when pelvic lymphadenectomy was
      performed (5.1% vs 0.9%, P < 0.01). The analysis of the 212 patients (52.2%) in
      the Bookwalter group showed higher frequency of nerve injury in the patients
      undergoing pelvic lymphadenectomy (7.8% vs 2.0%, P = 0.05). In the second period,
      femoral nerve injury was observed in 1 (0.7%) of 132 patients operated on and in
      1 (2.3%) of 43 patients (32.6%) in the Bookwalter group. When comparing the 2
      periods, the lesser use of the Bookwalter retractor and the reduced time of
      maximal traction of the pelvic blades decreased the nerve injury rate from 2.7%
      to 0.7% and, in the Bookwalter group, from 5.1% to 2.3%. These results, although
      not statistically significant, are clinically relevant. CONCLUSIONS: Femoral
      nerve injury during gynecologic cancer surgery was associated with the Bookwalter
      retractor. The pelvic blades of the retractor may exert a compression on the
      nerve. The weakened muscles suggest that the nerve compression occurred
      intrapelvically over the iliacus muscle. Shortening the time of maximal traction
      of the pelvic blades reduced the incidence of femoral nerve injury. When
      performing gynecologic surgery with the use of the Bookwalter retractor, care
      must taken with the placement of the pelvic blades.

PMID- 24905615
TI  - Zambian women's experiences and understanding of cervical cancer: a qualitative
      study.
AB  - OBJECTIVE: Cervical cancer is the most common cancer in Zambian women, and
      approximately 28% of all patients with cancer seen at the Cancer Diseases
      Hospital in Lusaka experience this disease. Our objective was to gain insight
      into the knowledge, understanding, and experiences of women treated for cervical
      cancer at the specific hospital. METHODS: We selected a qualitative research
      design and descriptive phenomenological approach for the study. Twenty-one (n =
      21) semistructured interviews directed by an interview schedule were conducted.
      We used Patton's open coding steps and a template analyses style guided by the 4
      themes of the interview schedule to analyze the data. RESULTS: Most participants
      indicated that they did not know and understand anything of cervical cancer. They
      believed they were bewitched and consulted traditional healers and used
      traditional medicine. Most described that they experienced symptoms for extended
      periods of time before they were diagnosed. They described how the offensive
      vaginal bleeding and watery discharge they experienced led to isolation,
      rejection, and humiliation. The participants said they did not understand how
      they would be treated and treatment was described as a terrible experience.
      CONCLUSIONS: The women's lived experiences of cervical cancer tell of severe
      suffering. They knew and understood very little about this disease. Their
      suffering became so unbearable that some wanted to end their lives. They were
      subjected to the opinions of others who knew equally as little but were quite
      willing to speak out, judge, and reject. Most battled through the treatment and
      the distressing adverse effects because it was their only hope to become better.
      RECOMMENDATIONS: Zambian women must be empowered with knowledge and skills to
      protect themselves against cervical cancer. Suggestions for improving outcomes
      include changing high-risk behavior, taking advantage of screening opportunities,
      recognizing the signs of cervical cancer, and seeking health care without delay.

PMID- 24905616
TI  - Can pelvic lymphadenectomy be omitted in stage IA2 to IIB uterine cervical
      cancer?
AB  - OBJECTIVES: The aims of this study were to predict pelvic lymph node metastasis
      in uterine cervical cancer before surgery and to evaluate the potential efficacy
      of omitting pelvic lymphadenectomy. MATERIALS AND METHODS: A total of 163
      patients with invasive uterine cervical cancer in FIGO stage IA2 to IIB, all of
      whom underwent primary radical hysterectomy with pelvic lymphadenectomy,
      participated in this study. RESULTS: The incidences of pelvic lymph node
      metastasis in stage IA2, stage IB1, stage IB2, stage IIA, and stage IIB cervical
      cancer were 0% (0/12), 17% (13/76), 22% (6/27), 33% (8/24), and 63% (15/24),
      respectively. A significant difference was observed in overall survival with
      nodal metastasis status (P < 0.0001). Univariate analysis revealed that
      parametrial invasion (P < 0.0001), tumor markers (P = 0.0006), tumor size greater
      than 2 cm (P < 0.0001), tumor size less than 3 cm (P = 0.0009), and tumor size
      greater than 4 cm (P = 0.0024) were correlated with pelvic lymph node metastasis.
      However, multivariate analysis revealed that parametrial invasion (P = 0.01; odds
      ratio, 3.37; 95% confidence interval, 1.31-9.0) and tumor size greater than 2 cm
      (P = 0.005; odds ratio, 4.93; 95% confidence interval, 1.54-22.01) were
      independently associated with nodal metastasis. CONCLUSIONS: Pelvic
      lymphadenectomy may be avoided in patients with negative parametrial invasion and
      a tumor size less than 2 cm, thereby minimizing postoperative complications.

PMID- 24905617
TI  - Analysis of patients with stage IIIC endometrial cancer.
AB  - OBJECTIVE: We aimed to define the factors that are related to recurrence and
      survival in patients with stage IIIC endometrial carcinoma in this study.
      MATERIALS AND METHODS: A total of 147 patients who underwent staging surgery and
      had a diagnosis of stage IIIC1 to IIIC2 endometrial cancer according to the
      International Federation of Gynecology and Obstetrics 2009 were included.
      Patients whose data could not be obtained and patients with a diagnosis of
      uterine sarcoma and with synchronous tumors were excluded. RESULTS: Mean age of
      the patients was 58.6 years. Among these patients, 63 had stage IIIC1 and 84 had
      stage IIIC2 disease. Extrauterine spread was detected in 22% of the patients.
      Median number of paraaortic (PA) and pelvic lymph nodes removed were 16.5 and 38,
      respectively. Paraaortic and pelvic nodal involvements were detected in 84
      patients and 125 patients, respectively. Radiotherapy was applied more commonly
      as an adjuvant therapy. Three-year progression-free survival (PFS) and 3-year
      disease-specific survival (DSS) were 65% and 84%, respectively. Seventy percent
      of the recurrences were outside the pelvis. Site of metastatic lymph nodes and
      the number of metastatic PA lymph nodes were associated with 3-year PFS and
      lymphovascular space invasion; site of metastatic lymph nodes and the presence of
      recurrence were associated with 3-year DSS in the univariate analysis. Although
      any surgicopathological factor was not related to 3-year PFS, only the presence
      of recurrence was an independent prognostic factor for a 3-year DSS in the
      multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002
      0.183). CONCLUSIONS: The number of debulked metastatic lymph nodes and PA
      involvement were associated with recurrence in the univariate analysis. The
      presence of recurrence was the only independent prognostic factor detecting
      survival. Therefore, systematic lymphadenectomy involving PA lymph nodes instead
      of sampling should be performed in patients with high risk for nodal involvement
      in endometrial cancer.

PMID- 24905618
TI  - Patient preferences for side effects associated with cervical cancer treatment.
AB  - OBJECTIVES: The aim of this study was to assess patient preferences regarding
      side effects associated with cervical cancer treatment. METHODS/MATERIALS: The
      visual analog scale (VAS) and modified standard gamble (SG) were used to elicit
      preferences of women with no evidence of disease after primary treatment of
      cervical cancer. Higher scores on VAS and SG indicated more favorable ratings for
      a given health state. Health states (HS) included vaginal shortening, diarrhea,
      dietary changes, menopause, moderate nausea/vomiting, rectal bleeding, sexual
      dysfunction, and urinary self-catheterization. Descriptive statistics, Kruskal
      Wallis, Mann-Whitney U, and Wilcoxon signed-ranks tests and correlation
      coefficients were used for statistical analysis. RESULTS: Seventy-eight patients
      participated in the study. Median age was 44.1 years (range, 24.9-67.8 years).
      Median time since treatment completion was 31.2 months (range, 1.0-113.3 months).
      The HSs rated as most favorable by VAS were also rated as most favorable by SG.
      Increasing age was associated with higher VAS scores for menopause and vaginal
      shortening (P = 0.04 and 0.036). African Americans had higher VAS scores for
      dietary changes (P = 0.05), sexual dysfunction (P = 0.028), and diarrhea (P =
      0.05) when compared with Hispanic and non-Hispanic white patients. Women
      receiving radiation had more favorable VAS scores for menopause compared with
      women undergoing radical hysterectomy (P = 0.05). Women receiving chemotherapy
      rated urinary self-catheterization less favorably by VAS score compared with
      those not receiving chemotherapy (P = 0.045). CONCLUSIONS: Multiple demographic
      and clinical factors influence the severity of treatment-related adverse effects
      perceived by women surviving cervical cancer. A better understanding of factors
      influencing patient preferences regarding treatment side effects will allow
      providers to formulate care better tailored to the individual desires of each
      patient.

PMID- 24905619
TI  - Interleukin 1beta and interleukin 1 receptor antagonist gene polymorphisms and
      cervical cancer: a meta-analysis.
AB  - OBJECTIVES: Previous studies investigating the association between interleukin
      1beta (IL-1beta) and its receptor antagonist (IL-1RN) polymorphism and cervical
      cancer risk have reported controversial results. Thus, we examined these
      associations by performing meta-analyses. METHODS AND MATERIALS: Fourteen studies
      testing the association between IL-1beta and/or IL-1RN gene polymorphisms and
      cervical cancer were examined: 5 studies of IL-1beta-511C/T, 3 studies of IL
      1beta-31T/C, and 6 studies of IL-1RN. Overall and ethnicity-specific summary odds
      ratios (ORs) and corresponding 95% confidence intervals (CIs) for cervical cancer
      associated with these polymorphisms were estimated using fixed- and random
      effects models. Heterogeneity and publication bias were evaluated. RESULTS: Meta
      analysis of all 6 studies showed variant genotypes of IL-1RN to be associated
      with an elevated cervical cancer risk (RN2/RN2 vs RN1/RN1: OR, 2.64; 95% CI, 1.29
      5.40; recessive: OR, 2.15; 95% CI, 1.06-4.38; dominant: OR, 1.60; 95% CI, 1.07
      2.38). Combined analysis indicated that IL-1beta-511C/T polymorphism was also
      associated with increased risk of cervical cancer (TT vs CC: OR, 1.56; 95% CI,
      1.22-1.99; CT vs CC: OR, 1.61; 95% CI, 1.31-1.99; dominant: OR, 1.60; 95% CI,
      1.31-1.95). No significant association of IL-1beta-31T/C and cervical cancer risk
      was detected. There was no evidence of publication bias. CONCLUSIONS: This meta
      analysis suggested that the IL-1RN and IL-1beta-511C/T polymorphisms may
      contribute to genetic susceptibility of cervical cancer. More studies are needed
      to further evaluate the role of the IL-1beta-31T/C polymorphism in the etiology
      of cancer.

PMID- 24905620
TI  - Twelve serum proteins progressively increase with disease stage in squamous cell
      cervical cancer patients.
AB  - OBJECTIVE: This study aimed to reliably identify serum protein profile
      alterations that may be useful for elucidation of the disease mechanism and/or
      finding new targets for treatment and intervention. MATERIALS AND METHODS: A
      total of 1057 women at 4 different squamous cell cervical cancer stages
      (noninvasive, invasive International Federation of Gynecology and Obstetrics
      stages I, II, and III) were included in this cross-sectional study. Forty-seven
      serum proteins were profiled using multiplex Luminex immunoassays. RESULTS: Serum
      concentration of serum amyloid A (SAA), C-reactive protein (CRP), soluble tumor
      necrosis factor receptor I and II (sTNFRI and sTNFRII), soluble interleukin 2
      receptor alpha (sIL2Ralpha), CXCL1, CXCL9, hepatocyte growth factor, squamous
      cell carcinoma antigen (SCCA), insulin-like growth factor binding protein 2,
      CA125, and carcinoembryonic antigen (CEA) were elevated significantly as disease
      progressed in cervical cancer patients. Serum levels are significantly different
      at early stage (I) for SAA, CRP, sIL2Ralpha, sTNFRII, SCCA, and CEA (P values
      ranged from 0.02 for CEA to 0.0001 for CRP and SCCA) and at late stages (II and
      III) for all 12 proteins (P values ranged from 8.78E-5 for CA125 to 3.49E-47 for
      SAA), as compared to the noninvasive stage. The areas under the curves of these
      proteins for disease state separation also improved with the advancement of the
      disease. The correlations between serum concentrations of these proteins also
      show different patterns at different clinical stages. These proteins are involved
      in multiple mechanisms including inflammation and immunity, angiogenesis, growth
      promotion, and metastasis. CONCLUSIONS: A number of serum proteins are
      significantly different between patients at different stages of cervical cancer.

PMID- 24905621
TI  - Carotid chemoreceptor afferent projections to leptin receptor containing neurons
      in nucleus of the solitary tract.
AB  - Neurons expressing the leptin receptor (Ob-R) exist within the caudal nucleus of
      the solitary tract (NTS). Additionally, afferent neurons expressing the Ob-R have
      been identified within the nodose ganglion and NTS. Furthermore, systemic
      injections or focal injections of leptin directly into NTS potentiate the
      response of NTS neurons to carotid chemoreceptor activation. However, the
      distribution of carotid body afferents in relation to Ob-R containing neurons
      within NTS is not known. In this study, chemoreceptor afferent fibers were
      labeled following microinjection of the anterograde tract tracer biotinylated
      dextran amine (BDA) into the carotid body or petrosal/nodose ganglion of Wistar
      rats. After a survival period of 10-14 days, the NTS was processed for BDA and Ob
      R immunoreactivity. Afferent axons originating in the carotid body were found to
      project to the lateral (Slt), gelantinosa (Sg), and medial (Sm) subnuclei of the
      NTS complex. A similar, but more robust distribution of BDA labeled fibers was
      observed in the NTS complex after injections into the petrosal/nodose ganglion.
      Carotid body BDA labeled fibers were observed in close apposition to Ob-R
      immunoreactive neurons in the region of Slt, Sg and Sm. In addition, a small
      number of carotid body afferents were found to contain both BDA and express Ob-R
      like immunoreactivity within the regions of Slt, Sg and Sm. Taken together, these
      data suggest that leptin may modulate carotid chemoreceptor function not only
      through direct effects on NTS neurons, but also through a direct effect on
      carotid body primary afferent fibers that innervate NTS neurons. 

PMID- 24905622
TI  - Plasma copeptin level predicts acute traumatic coagulopathy and progressive
      hemorrhagic injury after traumatic brain injury.
AB  - Higher plasma copeptin levels correlate with poor clinical outcomes after
      traumatic brain injury. Nevertheless, their links with acute traumatic
      coagulopathy and progressive hemorrhagic injury are unknown. Therefore, we aimed
      to investigate the relationship between plasma copeptin levels, acute traumatic
      coagulopathy and progressive hemorrhagic injury in patients with severe traumatic
      brain injury. We prospectively studied 100 consecutive patients presenting within
      6h from head trauma. Progressive hemorrhagic injury was present when the follow
      up computerized tomography scan reported any increase in size or number of the
      hemorrhagic lesion, including newly developed ones. Acute traumatic coagulopathy
      was defined as an activated partial thromboplastic time greater than 40s and/or
      international normalized ratio greater than 1.2 and/or a platelet count less than
      120*10(9)/L. We measured plasma copeptin levels on admission using an enzyme
      linked immunosorbent assay in a blinded fashion. In multivariate logistic
      regression analysis, plasma copeptin level emerged as an independent predictor of
      progressive hemorrhagic injury and acute traumatic coagulopathy. Using receiver
      operating characteristic curves, we calculated areas under the curve for
      progressive hemorrhagic injury and acute traumatic coagulopathy. The predictive
      performance of copeptin was similar to that of Glasgow Coma Scale score. However,
      copeptin did not obviously improve the predictive value of Glasgow Coma Scale
      score. Thus, copeptin may help in the prediction of progressive hemorrhagic
      injury and acute traumatic coagulopathy after traumatic brain injury. 

PMID- 24905623
TI  - Adipokinetic hormone induces changes in the fat body lipid composition of the
      beetle Zophobas atratus.
AB  - In insects, neuropeptide adipokinetic hormone (AKH) released from the corpora
      cardiaca mobilizes lipids and carbohydrates in the fat body. We examined the
      developmental differences in the action of Tenmo-AKH, a bioanalogue belonging to
      the adipokinetic/hypertrahelosemic family (AKH/HrTH), on the lipid composition of
      larval and pupal fat bodies in the beetle Zophobas atratus. Tenmo-AKH was
      administered to the beetle larvae and pupae either as a single dose or as two
      doses of 20 pmol during a 24h interval. Extracts of fat bodies were used to
      analyse the lipid composition by gas chromatography (GC) combined with mass
      spectrometry (GC-MS). Control extracts were analyzed using the same method. Fatty
      acids (FA) and fatty acid methyl esters (FAME) were the most abundant compounds
      in the fat bodies from both developmental stages. We observed significant
      differences in their concentrations following hormonal treatment. Tenmo-AKH also
      induced a distinct increase in larval sterols, fatty alcohols and benzoic acid.

PMID- 24905624
TI  - High post-transplant virological response in hepatitis C virus infected patients
      treated with pretransplant protease inhibitor-based triple therapy.
AB  - BACKGROUND & AIMS: Prevention of recurrent hepatitis C virus (HCV) following
      liver transplant (LT) with pre-LT antiviral therapy is limited by poor
      tolerability and efficacy. We aimed to evaluate the safety and efficacy of NS3/4A
      protease inhibitor (PI)-based triple therapy in patients awaiting LT. METHODS:
      Consecutive patients treated with triple therapy pre-LT from two centers were
      prospectively enrolled in an observational cohort. Overall 12 week sustained
      virological response (SVR12) was the primary outcome. Pre- and post-LT (pTVR)
      virological response rates and safety were secondary outcomes. RESULTS: Twenty
      nine patients (mean age 57.9, 79% male, 66% prior non-responders) were treated
      with telaprevir (93%) or boceprevir-based (7%) triple therapy for a median
      (range) of 27 (3-50) weeks, including a pegylated-interferon and ribavirin lead
      in in 18%. Median (range) MELD at treatment was 8 (6-16), 39% had hepatocellular
      carcinoma and all patients were Child-Turcotte-Pugh class A (62%) or B (38%).
      Twelve patients underwent LT, 75% with undetectable viral load. The overall SVR12
      rate was 52%, including pre-LT SVR12 of 41% in patients who completed treatment
      and follow-up on the wait list and pTVR12 of 67% among transplanted patients. The
      pTVR12 rate was 89% among those patients with undetectable viral load at LT.
      Serious adverse events occurred in nine (31%) patients including one (3%) on
      treatment death and eight (28%) hospitalizations. CONCLUSIONS: Overall SVR12 and
      pTVR12 rates are high among patients treated with PI-based triple therapy while
      awaiting LT, even in this difficult to treat population. However, caution is
      needed as early discontinuation and serious adverse events are common.

PMID- 24905625
TI  - A semicircular controlled cortical impact produces long-term motor and cognitive
      dysfunction that correlates well with damage to both the sensorimotor cortex and
      hippocampus.
AB  - Animal models of traumatic brain injury (TBI) are essential for testing novel
      hypotheses and therapeutic interventions. Unfortunately, due to the broad
      heterogeneity of TBI in humans, no single model has been able to reproduce the
      entire spectrum of these injuries. The controlled cortical impact (CCI) model is
      one of the most commonly used models of contusion TBI. However, behavioral
      evaluations have revealed transient impairment in motor function after CCI in
      rats and mice. Here we report a new semicircular CCI (S-CCI) model by increasing
      the impact tip area to cover both the motor cortex and hippocampal regions in
      adult mice. Mice were subjected to S-CCI or CCI using an electromagnetic impactor
      (Impactor One, MyNeuroLab; semicircular tip: 3mm radius; CCI tip diameter: 3mm).
      We showed that S-CCI, at two injury severities, significantly decreased the
      neuroscore and produced deficits in performance on a rotarod device for the
      entire duration of the study. In contrast, the CCI induced motor deficits only at
      early stages after the injury, suggesting that the S-CCI model produces long
      lasting motor deficits. Morris water maze test showed that both CCI and S-CCI
      produced persisting memory deficits. Furthermore, adhesive removal test showed
      significant somatosensory and motor deficits only in the S-CCI groups.
      Histological analysis showed a large extent of cortical contusion lesions,
      including both the sensory and motor cortex, and hippocampal damage in the S-CCI.
      These findings collectively suggest that the current model may offer sensitive,
      reliable, and clinically relevant outcomes for assessments of therapeutic
      strategies for TBI.

PMID- 24905626
TI  - Age-related differences in working memory evoked gamma oscillations.
AB  - OBJECTIVE: Working memory is associated with gamma oscillations (30-50 Hz).
      Previous studies have demonstrated altered gamma oscillations in the elderly
      population that may be related to general cognitive decline. However, it is
      unknown how gamma oscillations change with age or if there is an age when gamma
      oscillations optimally mediate working memory performance. That is, gamma
      oscillations may be maximal in middle-aged adults compared to younger and elderly
      adults. The objective of this study was to evaluate working memory evoked gamma
      oscillations in adults aged 19-29 years (mean 23.32 +/- 2.85 1 SD) compared to
      adults aged 30-60 years (mean 39.10 +/- 8.11 1 SD). METHODS: Subjects completed
      the verbal N-back task administered at four working loads (0, 1, 2, 3), while
      electroencephalography (EEG) was collected. Gamma power was measured during
      correct responses. RESULTS: Reduced gamma oscillations were observed in the
      adults aged 19-29 compared to those aged 30-60 years. Age was found to be
      positively related to the power of gamma oscillations. No differences were found
      on N-Back accuracy. CONCLUSIONS: Increased working memory evoked gamma
      oscillatory activity may provide a neurophysiological marker in the healthy aging
      brain.

PMID- 24905627
TI  - In-vivo detection of inflammation and neurodegeneration in the chronic phase
      after permanent embolic stroke in rats.
AB  - Neuroinflammation with microglia activation (MA) constitutes a key tissue
      response in acute stroke. Until now, its course in the chronic stage is less well
      defined. Here, we investigated (i) neuroinflammation in the chronic stage of a
      rat model of embolic stroke (n=6), and (ii) whether this process can be
      visualized in vivo by multimodal imaging using Magnetic Resonance Imaging (MRI)
      and Positron-Emission-Tomography (PET). Imaging data were verified using
      histology and immunohistochemistry. Repetitive PET studies until week 6 after
      stroke reveal poststroke inflammation as a dynamic process that involved the
      infarct, the surrounding tissue and secondary degenerating areas in a complex
      fashion. At the end, 7 months after stroke, neuroinflammation had almost
      completely vanished at the lesion side. In contrast, remote from the primarily
      infarcted areas, a marked T2(*)- hypointensity was detected in the ipsilateral
      thalamus. In the corresponding area, [(11)C]PK11195-PET detected microglia
      activation. Immunohistochemistry confirmed activated microglia in the ipsilateral
      thalamus with signs of extensive phagocytosis and iron deposition around plaque
      like amyloid deposition. Neuronal staining (NeuN) revealed pronounced neuronal
      loss as an endpoint of neurodegeneration in these areas. In conclusion, the data
      demonstrate not only ongoing thalamic neuroinflammation but also marked
      neurodegeneration remote from the lesion site in the chronic phase after stroke
      in rats. Both, neuroinflammation and neurodegeneration were accessible to (immuno
      ) histochemical methods as well as to in vivo methods using [(11)C]PK11195-PET
      and T2(*)-weighted MRI. Although the functional roles of these dynamic processes
      remain to be elucidated, ongoing destruction of neuronal tissue is conceivable.
      Its inhibition using anti-inflammatory substances may be beneficial in chronic
      post-stroke conditions, while multimodal imaging can be used to evaluate putative
      therapeutic effects in vivo.

PMID- 24905628
TI  - Pharmaceutical care of older people: what do older people want from community
      pharmacy?
AB  - OBJECTIVES: To explore older people's opinions of current community pharmacy
      provision and identify potential areas for improvement. METHODS: A pilot focus
      group was conducted to finalise the topic areas for discussion. Three focus
      groups and three small group interviews were held with a total of 25 people aged
      over 65 years. A purposive sampling approach was used to maximise variation in
      likely responses. All focus group discussions were transcribed and analysed for
      emerging themes. Data collection continued until saturation was reached. Finally,
      the themes were taken to a further five community groups to discuss and confirm
      the findings. KEY FINDINGS: Two main interlinked themes emerged around 'personal
      and relational factors' and 'service factors'. The participants valued continuity
      of personalised pharmaceutical care and described receiving this care in small
      community pharmacies. The ability to build a trusting relationship over time was
      important to the people in this study. There was a lack of awareness of services
      already available from community pharmacies. Ongoing disruption in the supply of
      medicines caused problems for this client group, and the complexity of
      prescription ordering, collection and delivery systems presented challenges for
      participants. Good communication from the community pharmacy helped to improve
      the experience. CONCLUSION: This study contributes some qualitative data on the
      opinions of older people about community pharmacies. There may be planning
      implications for the size of future community pharmacies and the range of
      services provided. Community pharmacies may need to take a more proactive role in
      promoting innovative services to older people who may benefit from these
      services.

PMID- 24905631
TI  - Hammock sign.

PMID- 24905629
TI  - Muscle uncoupling protein 3 expression is unchanged by chronic ephedrine/caffeine
      treatment: results of a double blind, randomised clinical trial in morbidly obese
      females.
AB  - Ephedrine/caffeine combination (EC) has been shown to induce a small-to-moderate
      weight loss in obese patients. Several mechanisms have been proposed, among which
      an increased thermogenic capacity of skeletal muscle consequent to the EC-induced
      up-regulation of uncoupling protein 3 (UCP3) gene expression. We did a parallel
      group double-blind, placebo-controlled, 4-week trial to investigate this
      hypothesis. Thirteen morbidly obese women (25-52 years of age, body-mass index
      48.0+/-4.0 kg/m2, range 41.1-57.6) were randomly assigned to EC (200/20 mg, n =
      6) or to placebo (n = 7) administered three times a day orally, before undergoing
      bariatric surgery. All individuals had an energy-deficit diet equal to about 70%
      of resting metabolic rate (RMR) diet (mean 5769+/-1105 kJ/day). The RMR analysed
      by intention to treat and the UCP3 (long and short isoform) mRNA levels in rectus
      abdominis were the primary outcomes. Body weight, plasma levels of adrenaline,
      noradrenaline, triglycerides, free fatty acids, glycerol, TSH, fT4, and fT3 were
      assessed, as well as fasting glucose, insulin and HOMA index, at baseline and at
      the end of treatments. Body weight loss was evident in both groups when compared
      to baseline values (overall -5.2+/-3.2%, p<0.0001) without significant
      differences between the treated groups. EC treatment increased the RMR (+9.2+/
      6.8%, p = 0.020), differently from placebo which was linked to a reduction of RMR
      (-7.6+/-6.5%, p = 0.029). No significant differences were seen in other metabolic
      parameters. Notably, no changes of either UCP3 short or UCP3 long isoform mRNA
      levels were evident between EC and placebo group. Our study provides evidence
      that 4-week EC administration resulted in a pronounced thermogenic effect not
      related to muscle UCP3 gene expression and weight loss in morbidly obese females
      under controlled conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02048215.

PMID- 24905632
TI  - Expert opinion: United States Preventive Services Task Force recommendation on
      screening for lung cancer.

PMID- 24905630
TI  - Manipulation of endogenous kinase activity in living cells using photoswitchable
      inhibitory peptides.
AB  - Optogenetic control of endogenous signaling can be an important tool for probing
      cell behavior. Using the photoresponse of the LOV2 domain of Avena sativa
      phototropin 1, we developed analogues of kinase inhibitors whose activity is
      light dependent. Inhibitory peptides were appended to the Jalpha helix, where
      they potently inhibited kinases in the light but were sterically blocked from
      kinase interaction in the dark. Photoactivatable inhibitors for cyclic-AMP
      dependent kinase (PKA) and myosin light chain kinase (MLCK) are described,
      together with studies that shed light on proper positioning of the peptides in
      the LOV domain. These inhibitors altered endogenous signaling in living cells and
      produced light-dependent changes in cell morphodynamics. 

PMID- 24905633
TI  - ACR appropriateness criteria(r) nonischemic myocardial disease with clinical
      manifestations (ischemic cardiomyopathy already excluded).
AB  - Nonischemic myocardial disease or cardiomyopathy can present as arrhythmia,
      palpitations, heart failure, dyspnea, lower extremity edema, ascites, syncope,
      and/or chest discomfort and can be classified as either systolic, diastolic, or a
      combination of both. Echocardiography is the mainstay of evaluating left
      ventricular function. However, cardiac magnetic resonance imaging (MRI) is now
      considered the reference standard imaging technique to assess myocardial anatomy,
      function, and viability. Advanced MRI techniques with delayed myocardial
      enhancement, especially, can provide information beyond echocardiography for
      tissue characterization in CM and can assist in determining specific etiology or
      in narrowing the differential. Often imaging enhancement patterns, signal
      characteristics, and morphology on MRI can lead to specific diagnoses such as
      amyloidosis, hypertrophic CM, or iron deposition. Cardiac computed tomography is
      usually used in excluding coronary artery disease but can also be used in some
      patients unable to undergo cardiac MRI to assess arrhythmogenic right ventricular
      dysplasia. Both 18-F-fluoro-2-deoxyglucose positron emission tomography and
      delayed contrast-enhanced MRI can be used to assess for cardiac sarcoidosis. The
      American College of Radiology Appropriateness Criteria are evidence-based
      guidelines for specific clinical conditions that are reviewed every 3 years by a
      multidisciplinary expert panel. The guideline development and review include an
      extensive analysis of current medical literature from peer-reviewed journals and
      the application of a well-established consensus methodology (modified Delphi) to
      rate the appropriateness of imaging and treatment procedures by the panel. In
      those instances in which evidence is lacking or not definitive, expert opinion
      may be used to recommend imaging or treatment. 

PMID- 24905634
TI  - Room temperature ferromagnetic (Fe1-xCox)3BO5 nanorods.
AB  - Cobalt-doped ferroferriborate ((Fe1-xCox)3BO5) nanorods (NRs) are synthesized by
      a one-pot high-temperature organic-solution-phase method. The aspect ratios of
      the NRs are tuned by the heating rate. These NRs form via anisotropic growth
      along twin boundaries of the multiply twinned nuclei. Magnetic properties are
      dramatically modified by Co substitutional doping, changing from
      antiferromagnetic order at low temperatures to ferromagnetic above room
      temperature, with a greatly enhanced magnetic ordering temperature. These
      anisotropic ferromagnetic NRs with a high ordering temperature may provide a new
      platform for understanding nanomagnetism and for magnetic applications. 

PMID- 24905635
TI  - Does exposure to a radiofrequency electromagnetic field modify thermal preference
      in juvenile rats?
AB  - Some studies have shown that people living near a mobile phone base station may
      report sleep disturbances and discomfort. Using a rat model, we have previously
      shown that chronic exposure to a low-intensity radiofrequency electromagnetic
      field (RF-EMF) was associated with paradoxical sleep (PS) fragmentation and
      greater vasomotor tone in the tail. Here, we sought to establish whether sleep
      disturbances might result from the disturbance of thermoregulatory processes by a
      RF-EMF. We recorded thermal preference and sleep stage distribution in 18 young
      male Wistar rats. Nine animals were exposed to a low-intensity RF-EMF (900 MHz, 1
      V x m(-1)) for five weeks and nine served as non-exposed controls. Thermal
      preference was assessed in an experimental chamber comprising three
      interconnected compartments, in which the air temperatures (Ta) were set to 24
      degrees C, 28 degrees C and 31 degrees C. Sleep and tail skin temperature were
      also recorded. Our results indicated that relative to control group, exposure to
      RF-EMF at 31 degrees C was associated with a significantly lower tail skin
      temperature (-1.6 degrees C) which confirmed previous data. During the light
      period, the exposed group preferred to sleep at Ta = 31 degrees C and the
      controls preferred Ta = 28 degrees C. The mean sleep duration in exposed group
      was significantly greater (by 15.5%) than in control group (due in turn to a
      significantly greater amount of slow wave sleep (SWS, +14.6%). Similarly,
      frequency of SWS was greater in exposed group (by 4.9 episodes.h-1). The PS did
      not differ significantly between the two groups. During the dark period, there
      were no significant intergroup differences. We conclude that RF-EMF exposure
      induced a shift in thermal preference towards higher temperatures. The shift in
      preferred temperature might result from a cold thermal sensation. The change in
      sleep stage distribution may involve signals from thermoreceptors in the skin.
      Modulation of SWS may be a protective adaptation in response to RF-EMF exposure.

PMID- 24905636
TI  - Shikonin inhibits prostate cancer cells metastasis by reducing matrix
      metalloproteinase-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways.
AB  - Metastasis is one of the most important factors related to prostate cancer
      therapeutic efficacy. In previous studies, shikonin, an active naphthoquinone
      isolated from the Chinese medicine Zi Cao, has various anticancer activities both
      in vivo and in vitro. However, the mechanisms underlying shikonin's anticancer
      activity are not fully elucidated on prostate cancer cells. In the present study,
      we aimed to investigate the potential effects of shikonin on prostate cancer
      cells and the underlying mechanisms by which shikonin exerted its actions. With
      cell proliferation, flow cytometric cell cycle, migration and invasion assays, we
      found that shikonin potently suppressed PC-3 and DU145 cell growth by cell cycle
      arrest at the G2 phase and metastasis in a dose-dependent manner. Mechanically,
      we presented that shikonin could suppress the metastasis of PC-3 and DU145 cells
      via inhibiting the matrix metalloproteinase-2 (MMP-2) and MMP-9 expression and
      activation. In addition, shikonin significantly decreased the phosphorylation of
      AKT and mTOR in a dose-dependent manner while it induced extracellular signal
      regulated kinase (ERK), p38 mitogen activated protein kinase (MAPK) and c-Jun N
      terminal kinase (JNK) phosphorylation. Further investigation of the underlying
      mechanism revealed that shikonin also induced the production of reactive oxygen
      species (ROS) that was reversed by the ROS scavenger dithiothreitol (DTT).
      Additionally, DTT reversed the shikonin induced activation of ERK1/2, thereby
      maintaining MMP-2 and MMP-9 expression and restoring cell metastasis. Together,
      shikonin inhibits aggressive prostate cancer cell migration and invasion by
      reducing MMP-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways and presents a
      potential novel alternative agent for the treatment of human prostate cancer. 

PMID- 24905638
TI  - An analysis of the feasibility of carbon management policies as a mechanism to
      influence water conservation using optimization methods.
AB  - Studies of how carbon reduction policies would affect agricultural production
      have found that there is a connection between carbon emissions and irrigation.
      Using county level data we develop an optimization model that accounts for the
      gross carbon emitted during the production process to evaluate how carbon
      reducing policies applied to agriculture would affect the choices of what to
      plant and how much to irrigate by producers on the Texas High Plains. Carbon
      emissions were calculated using carbon equivalent (CE) calculations developed by
      researchers at the University of Arkansas. Carbon reduction was achieved in the
      model through a constraint, a tax, or a subsidy. Reducing carbon emissions by 15%
      resulted in a significant reduction in the amount of water applied to a crop;
      however, planted acreage changed very little due to a lack of feasible
      alternative crops. The results show that applying carbon restrictions to
      agriculture may have important implications for production choices in areas that
      depend on groundwater resources for agricultural production. 

PMID- 24905637
TI  - Linkage of a de-identified United States rheumatoid arthritis registry with
      administrative data to facilitate comparative effectiveness research.
AB  - OBJECTIVE: Linkages between registries and administrative data may provide a
      valuable resource for comparative effectiveness research. However, personal
      identifiers that uniquely identify individuals are not always available. Here we
      describe methods to link a de-identified arthritis registry and US Medicare data.
      The linked data set was also used to evaluate the generalizability of the
      registry to the US Medicare population. METHODS: Rheumatoid arthritis (RA)
      patients participating in the Consortium of Rheumatology Researchers of North
      America (CORRONA) registry were linked to Medicare data restricted to
      rheumatology claims or claims for RA. Deterministic linkage was performed using
      age, sex, provider identification number, and geographic location of the CORRONA
      site. We then searched for visit dates in Medicare matching visit dates in
      CORRONA, requiring >=1 exact matching date. Linkage accuracy was quantified as a
      positive predictive value in a subcohort (n = 1,581) with more precise
      identifiers. RESULTS: CORRONA participants with self-reported Medicare (n =
      11,001) were initially matched to 30,943 Medicare beneficiaries treated by
      CORRONA physicians. A total of 8,431 CORRONA participants matched on >=1 visit;
      5,317 matched uniquely on all visits. The number of patients who linked and
      linkage accuracy (from the subcohort) were high for patients with >2 visits (n =
      3,458, 98% accuracy), exactly 2 visits (n = 822, 96% accuracy), and 1 visit (n =
      1,037, 79% accuracy) that matched exactly on calendar date. Demographics and
      comorbidity profiles of registry participants were similar to nonparticipants,
      except participants were more likely to take disease-modifying antirheumatic
      drugs and biologic agents. CONCLUSION: Linkage between a national, de-identified
      outpatient arthritis registry and Medicare data on multiple nonunique identifiers
      appears feasible and valid.

PMID- 24905639
TI  - Cysteine-grafted nonwoven geotextile: a new and efficient material for heavy
      metals sorption--Part B.
AB  - The development of a new material designed to trap heavy metals from sediments or
      wastewater, based on a polypropylene non-woven covalently grafted with cysteine,
      has been reported in a previous paper (Part A). The non-woven was first
      functionalized with acrylic acid (AA) which is used as spacer, and then cysteine
      was immobilized on the substrate through covalent coupling in order to obtain the
      so-called PP-g-AA-cysteine. Some preliminary heavy metals adsorption tests gave
      interesting results: at 20  degrees C for 24 h and in a 1000 mg/L heavy metals
      solution, PP-g-AA-cysteine adsorbs 95 mg Cu/g PP (CuSO4 solution), 104 mg Cu/g PP
      (Cu(NO3)2 solution), 135 mg Pb/g PP (Pb(NO3)2 solution) and 21 mg Cr/g PP
      (Cr(NO3)3 solution). In this second part of the work, heavy metals sorption tests
      were carried out with Cu (II), Pb (II), and Cr (III) separately, in order to
      determine the sorption capacity of this new sorbent as a function of (i) the
      heavy metals concentration in the solution, (ii) the contact time with the
      solution, (iii) the pH and (iv) the ionic strength of the solution containing
      heavy metals. Moreover, the sorption capacity of PP-g-AA-Cysteine was studied
      using a polluted solution consisting of a mixture of these different heavy
      metals. An Electron Paramagnetic Resonance study was finally carried out in order
      to determine the coordination geometry in the environment of the copper trapped
      by the PP-g-AA-cysteine. 

PMID- 24905640
TI  - Solarization and biosolarization using organic wastes for the bioremediation of
      soil polluted with terbuthylazine and linuron residues.
AB  - Strategies for remediation of polluted soils are needed to accelerate the
      degradation and natural attenuation of pesticides. This study was conducted to
      assess the effect of solarization (S) and biosolarization (BS) during the summer
      season using organic wastes (composted sheep manure and sugar beet vinasse) for
      the bioremediation of soil containing residues of terbuthylazine and linuron. The
      results showed that both S and BS enhanced herbicide dissipation rates compared
      with the non-disinfected control, an effect which was attributed to the increased
      soil temperature and organic matter. Linuron showed similar behavior under S and
      BS conditions. However, terbuthylazine was degraded to a greater extent in the
      biosolarization experiment using sugar beet vinasse than in the both the
      solarization and biosolarization experiments using composted sheep manure
      treatments. The main organic intermediates detected during the degradation of
      terbuthylazine and linuron were identified, enabling the main steps of
      degradation to be proposed. The results confirm that both S and BS techniques can
      be considered as a remediation tools for polluted soils containing these
      herbicides. 

PMID- 24905641
TI  - Silage effluent management: a review.
AB  - Silage effluent is a potent wastewater that can be produced when ensiling crops
      that have a high moisture content (MC). Silage effluent can cause fish-kills and
      eutrophication due to its high biochemical oxygen demand (BOD) and nutrient
      content, respectively. It has a high acidity (pH ~ 3.5-5) making it corrosive to
      steel and damaging to concrete, which makes handling, storage and disposal a
      challenge. Although being recognized as a concentrated wastewater, most research
      has focused on preventing its production. Despite noted imprecision in effluent
      production models-and therefore limited ability to predict when effluent will
      flow-there has been little research aimed at identifying effective reactive
      management options, such as containment and natural treatment systems. Increasing
      climate variability and intensifying livestock agriculture are issues that will
      place a greater importance on developing comprehensive, multi-layered management
      strategies that include both preventative and reactive measures. This paper
      reviews important factors governing the production of effluent, approaches to
      minimize effluent flows as well as treatment and disposal options. The challenges
      of managing silage effluent are reviewed in the context of its chemical
      constituents. A multi-faceted approach should be utilized to minimize
      environmental risks associated with silage effluent. This includes: (i) managing
      crop moisture content prior to ensiling to reduce effluent production, (ii)
      ensuring the integrity of silos and effluent storages, and (iii) establishing
      infrastructure for effluent treatment and disposal. A more thorough investigation
      of constructed wetlands and vegetated infiltration areas for treating dilute
      silage effluent is needed. In particular, there should be efforts to improve
      natural treatment system design criteria by identifying pre-treatment processes
      and appropriate effluent loading rates. There is also a need for research aimed
      at understanding the effects of repeated land application of effluent on soil
      quality and crop yields, as spreading is a common disposal practice. 

PMID- 24905642
TI  - Suitability of Miscanthus species for managing inorganic and organic contaminated
      land and restoring ecosystem services. A review.
AB  - The mitigation of potential health hazards and land scarcity due to land use
      change can be addressed by restoring functional and ecosystem services of
      contaminated land. Physico-chemical remediation options are criticized as being
      costly and not providing environment-friendly solutions. The use of plants and
      associated microorganisms could be a sustainable, cost-effective option to reduce
      pollutant exposure. Phytomanagement aims at using valuable non-food crops to
      alleviate environmental and health risks induced by pollutants, and at restoring
      ecosystem services. Suitable plant species must be tolerant to contaminants,
      reduce their transfer into the food chain, and efficiently produce marketable
      biomass. Based on Miscanthus' capacity to sequestrate inorganic contaminants into
      the root system and to induce dissipation of persistent organic contaminants in
      soil, these plant species are favorable for phytostabilization and
      phytodegradation. Among Miscanthus species, the noninvasive hybrid Miscanthus *
      giganteus, with a high lignocellulosic content, is a promising biomass crop for
      the bio-economy, notably the biorefinery and bioenergy industries. Planting this
      species on contaminated and marginal land is a promising option to avoid changes
      in arable land use to mitigate the food vs. biofuel controversy. Key issues in
      promoting sustainable management of Miscanthus sp. on contaminated land are: (a)
      crop suitability, integration, and sustainability in a region with a potential
      local market; (b) site suitability in relation to the species' requirements and
      potential, (c) biotic interactions in the landscape diversity; and (d) increase
      in shoot yields in line with various stressors (e.g., pollutants, drought, cold
      temperatures), and with minimal inputs. 

PMID- 24905643
TI  - A high throughout semi-quantification method for screening organic contaminants
      in river sediments.
AB  - A high throughout semi-quantification method for screening nearly 900 organic
      contaminants (OCs) in river sediments has been developed. For most OCs tested,
      concentrations calculated from the proposed semi-quantification method deviated
      from actual values by a factor of 4. The overall recovery tests indicated that
      most OCs can be successfully extracted from sediments with recovery rates from
      84.1 to 128.6%. To demonstrate the effectiveness of our method towards OC
      quantification, we screened OCs from sediments collected from the Haihe River
      basin. Seventy unregulated OCs (including pesticides, flame retardants, PPCPs,
      etc.) were identified and quantified at concentrations up to 2600 ng/g from 24
      sediment samples. From these results, it is confirmed that the developed method
      is a useful way to fulfill a comprehensive analysis of OCs in sediments and would
      be valuable for the identification and prioritization of priority pollutants in
      watershed management. 

PMID- 24905644
TI  - Mapping and monitoring High Nature Value farmlands: challenges in European
      landscapes.
AB  - The importance of low intensity farming for the conservation of biodiversity
      throughout Europe was acknowledged early in the 1990s when the concept of 'High
      Nature Value farmlands' (HNVf) was devised. HNVf has subsequently been given high
      priority within the EU Rural Development Programme. This puts a requirement on
      each EU Member State not only to identify the extent and condition of HNVf within
      their borders but also to track trends in HNVf over time. However, the diversity
      of rural landscapes across the EU, the scarcity of (adequate) datasets on
      biodiversity, land cover and land use, and the lack of a common methodology for
      HNVf mapping currently represent obstacles to the implementation of the HNVf
      concept across Europe. This manuscript provides an overview of the
      characteristics of HNVf across Europe together with a description of the
      development of the HNVf concept. Current methodological approaches for the
      identification and mapping of HNVf across EU-27 and Switzerland are then
      reviewed, the main limitations of these approaches highlighted and
      recommendations made as to how the identification, mapping and reporting of HNVf
      state and trends across Europe can potentially be improved and harmonised. In
      particular, we propose a new framework that is built on the need for strategic
      HNVf monitoring based on a hierarchical, bottom-up structure of assessment units,
      coincident with the EU levels of political decision and devised indicators, and
      which is linked strongly to a collaborative European network that can provide the
      integration and exchange of data from different sources and scales under common
      standards. Such an approach is essential if the scale of the issues facing HNVf
      landscapes are to be identified and monitored properly at the European level.
      This would then allow relevant agri-environmental measures to be developed,
      implemented and evaluated at the scale(s) required to maintain the habitats and
      species of high nature conservation value that are intimately associated with
      those landscapes. 

PMID- 24905645
TI  - Household's willingness to pay for arsenic safe drinking water in Bangladesh.
AB  - This study examines willingness to pay (WTP) in Bangladesh for arsenic (As) safe
      drinking water across different As-risk zones, applying a double bound discrete
      choice value elicitation approach. The study aims to provide a robust estimate of
      the benefits of As safe drinking water supply, which is compared to the results
      from a similar study published almost 10 years ago using a single bound
      estimation procedure. Tests show that the double bound valuation design does not
      suffer from anchoring or incentive incompatibility effects. Health risk awareness
      levels are high and households are willing to pay on average about 5 percent of
      their disposable average annual household income for As safe drinking water.
      Important factors influencing WTP include the bid amount to construct communal
      deep tubewell for As safe water supply, the risk zone where respondents live,
      household income, water consumption, awareness of water source contamination,
      whether household members are affected by As contamination, and whether they
      already take mitigation measures. 

PMID- 24905646
TI  - Are there different requirements for trace elements in eumelanin- and pheomelanin
      based color production? A case study of two passerine species.
AB  - Melanin is the most common pigment in animal integuments including bird plumage.
      It has been shown that several trace elements may play roles in the production
      and signaling function of melanin-colored plumage. We investigated coloration and
      content of various metal elements in the rectrices of two insectivorous
      passerines, Common Redstarts (Phoenicurus phoenicurus) and Blackcaps (Sylvia
      atricapilla), which have eumelanin- and pheomelanin-based coloration,
      respectively. We hypothesized that 1) the two species would differ in
      concentrations of metals important in melanin synthesis (Ca, Fe, Cu, Zn), 2)
      differences in metal concentration levels would be related to feather coloration.
      Our study confirmed the first prediction and provides the first evidence that
      selected elements may play a greater role in pheomelanin than in eumelanin
      synthesis. Concentrations of three elements considered as important in melanin
      synthesis (Ca, Fe, Zn) were 52% to 93% higher in rusty colored Common Redstart
      feathers compared to the dark gray Blackcap feathers. However, element
      concentrations were not correlated with feather coloration or sex in either
      species. Our study suggests that, of the two melanin forms, pheomelanin synthesis
      may bear higher costs associated with the acquisition of specific elements or
      limited elements may create trade-offs between ornamentation and other
      physiological functions. Our findings warrant further investigations designed to
      better understand the roles of macro- and microelements in the synthesis of both
      forms of melanin. 

PMID- 24905647
TI  - PHA-induced inflammation is not energetically costly in the subterranean rodent
      Ctenomys talarum (tuco-tucos).
AB  - Immune activity has been proposed to be associated with substantial costs, due to
      trade-offs with other functions or activities that share common resources and
      contribute to an animal's fitness. However, direct estimates of the cost of
      mounting an immune response are few and have been performed mainly in birds.
      Thus, further work is needed to clarify the relative costs of different
      components of the immune system and the role of environmental and life-history
      traits in modulating the costs of resistance. Within the components of immunity,
      inflammation is considered to be associated with a larger energetic expenditure.
      Here, we evaluated the energetic cost of the inflammatory response to
      phytohemagglutinin (PHA) in a wild population of a subterranean rodent, Ctenomys
      talarum, and the trade-offs between immune activity and reproduction. C. talarum
      develops an inflammatory response to PHA, but contrary to our predictions, this
      response was not associated with an increase in oxygen consumption regardless of
      reproductive status or sex. Our study shows that an immune challenge may not
      always result in a detectable energetic cost. We discuss the possibility that
      other currencies could be underlying the cost, such as micro-or macronutrients
      requirements, autoimmunity or oxidative stress. 

PMID- 24905648
TI  - Studies on the teratogenicity of anabasine in a rat model.
AB  - A number of plant toxins have been shown to be teratogenic to livestock. The
      teratogenic action of some of these alkaloids is mediated by nicotinic
      acetylcholine receptors (nAChR). However, for many of these alkaloids it is
      difficult to obtain sufficient quantities of individual alkaloids to perform
      teratology studies in livestock species. Therefore the objective of this study
      was to determine if a rat model can be utilized to characterize the teratogenic
      nature of individual plant toxins that are nAChR agonists. In this study, we
      evaluated the teratogenicity of anabasine by feeding pregnant rats anabasine
      containing rodent chow from gestational day (GD) 6-21. On GD21, the dams were
      euthanized and the gravid uteri were removed. The gravid uteri and individual
      pups were weighed. The pups were evaluated for bone malformations including cleft
      palate and scoliosis. Overall, the results of this study suggest that the rat is
      not a good model to study the teratogenicity of plant toxins that are nAChR
      agonists. It is possible that in the rat model, anabasine administered orally via
      the chow may not result in sufficient reduction in fetal movement to cause the
      significant malformations observed in livestock species. 

PMID- 24905649
TI  - Protein C activity in dogs envenomed by Vipera palaestinae.
AB  - Vipera palaestinae is responsible for most envenomations in humans and domestic
      animal in Israel. Its venom has pro- and anticoagulant properties. Protein C is a
      major natural anticoagulant, preventing excess clotting and thrombosis. This
      study investigated protein C activity and its prognostic value, as well as
      several other hemostatic analytes in dogs (Canis familiaris) accidently envenomed
      by V. palaestinae. Protein C activity was compared between envenomed dogs and 33
      healthy control dogs. Mean protein C was lower in dogs envenomed by V.
      palaestinae compared to controls (12.9% vs. 22.9%, respectively; P < 0.01). It
      was positively correlated with antithrombin activity (r = 0.3, P = 0.04), but not
      with other hemostatic analytes. The overall mortality rate was 13%, and at
      presentation no significant protein C activity difference was noted between
      survivors and non-survivors. A receiver operator characteristics analysis of
      protein C activity as a predictor of mortality had an area under the curve of 0.7
      (95% confidence interval 0.52-0.87). A protein C cutoff point of 8% corresponded
      to sensitivity and specificity of 70% and 57%, respectively. Dogs diagnosed with
      consumptive coagulopathy (14%) tended to have lower protein C activity compared
      to others; however, their mortality did differ from that of other dogs. This is
      the first study assessing protein C activity in V. palaestinae victims. Decreased
      protein C activity in such dogs may play a role in formation of thrombosis and
      hemostatic derangement as well as inflammation in V. palaestinae envenomations. 

PMID- 24905650
TI  - Expanding Flp-RMCE options: the potential of Recombinase Mediated Twin-Site
      Targeting (RMTT).
AB  - Where possible, developments enabling the establishment of cell lines with
      predictable, long-term stable expression capacity are based on single-copy
      integrations at safe genomic loci with predictable properties. Robust performance
      could be assigned to lentiviral transduction systems anchoring single LV-units at
      sites with adequate transcription potential. In the case of gene therapeutic
      vectors it is essential that the expression interval can be safely terminated
      following individual requirements, which has mostly been achieved by lox-mediated
      excision ("floxing"). To extend the spectrum of possible applications we replaced
      the common, phage-derived Cre/loxP-setup by modules derived from the yeast
      "Flp/FRT" site-specific recombination system. This change enables a variety of
      additional options, for instance by "multiplexing" strategies, which rely on a
      variety of heterospecific FRT-site variants (F'). If we provide lentiviral LTRs
      with a "twin-site", here an FF3 fusion, the presence of Flp-recombinase will
      effectively excise the expression cassette, leaving behind a single neutral,
      genomically anchored FF3 unit. This tag serves to identify the integration locus
      and to apply sequence- and structural (SIDD-) analyses to predict its functions.
      Candidate loci are then used to accommodate, at the given site, other genes of
      interest by "Recombinase-Mediated Twin Site Targeting" (RMTT), a contemporary
      extension of existing cassette exchange (RMCE-) routines. Supported by the fact
      that FF3 twins remain accessible within the host genome, RMTT provides access to
      certified cell lines as it complies with recently defined stringent genomic safe
      harbor criteria. Our discussion- and outlook-sections will cover lentiviral
      targeting strategies and current possibilities to enable their fine-tuning. 

PMID- 24905651
TI  - Cloning, characterization, expression analysis and inhibition studies of a novel
      gene encoding Bowman-Birk type protease inhibitor from rice bean.
AB  - This paper presents the first study describing the isolation, cloning and
      characterization of a full length gene encoding Bowman-Birk protease inhibitor
      (RbTI) from rice bean (Vigna umbellata). A full-length protease inhibitor gene
      with complete open reading frame of 327 bp encoding 109 amino acids was cloned
      from rice bean seeds using degenerate primer set. BlastP search revealed that the
      RbTI encoded amino acid of approx 13.0 kDa and shared 99% homology each with BBI
      from Phaseolus parvulus, Vigna trilobata and Vigna vexilata. Phylogenetic tree
      also showed close relationship of RbTI with BBI from other members of
      Leguminaceae family. RbTI gene was further confirmed as intronless (GenBank
      accession no. KJ159908). The secondary and 3D-structural models for the RbTI were
      predicted with homology modeling. qRT-PCR studies revealed the highest RbTI
      expression in the seeds nearing maturity, whereas the low expression of the gene
      was noticed in young leaves. The isolated RbTI was successfully expressed in
      Escherichiacoli and the highest expression was recorded after 5.5h of induction.
      Study on the inhibitory activity of expressed protein against the gut proteases
      of Hessian fly larvae revealed 87% inhibition. The novel RbTI gene will further
      broaden the pool of plant defense genes and could be an ideal choice for
      developing transgenic crops resistant to insect pests with high economic value.
      In addition, it has the potential to be used as a probe for selection of insect-
      and pathogen-resistant genotypes.

PMID- 24905652
TI  - Nucleotide diversity of Pita, a major blast resistance gene and identification of
      its minimal promoter.
AB  - Improvement of host plant resistance is one of the best methods to protect the
      yield from biotic stresses. Incorporation of major resistance genes or their
      variants into elite rice varieties will enhance the host plant resistance and its
      durability. Allele mining is a preferred choice to discover the novel allelic
      variants of major genes from wide range of germplasm. 'True' allele mining
      includes coding and noncoding regions, which are known to affect the plant
      phenotype, eventually. In this study, major blast resistance gene, Pita was
      analyzed by allele and promoter mining strategy and its different allelic
      variants were discovered from landraces and wild Oryza species. Polymorphisms at
      allelic sequences as well as transcription factor binding motif (TFBM) level were
      examined. At motif level, MYB1AT is present in Pita(Tadukan) and other resistance
      alleles, but was absent in the susceptible allele. Core promoter was demarked
      with 449 bp, employing serial promoter deletion strategy. Promoter with 1592 bp
      upstream region could express the gfp two fold higher than the core promoter. The
      identified Pita resistance allele (Pita(Konibora)) can be directly used in rice
      blast resistance breeding programs. Moreover, characterization of Pita core
      promoter led to deeper understanding of resistance gene's regulation and the
      identified core promoter can be utilized to express similar genes in rice.

PMID- 24905653
TI  - Carvedilol has stronger anti-inflammation and anti-virus effects than metoprolol
      in murine model with coxsackievirus B3-induced viral myocarditis.
AB  - AIMS: This study aims to compare the effects of carvedilol and metoprolol in
      alleviating viral myocarditis (VMC) induced by coxsackievirus B3 (CVB3) in mice.
      METHODS: A total of 116 Balb/c mice were included in this study. Ninety-six mice
      were inoculated intraperitoneally with CVB3 to induce VMC. The CVB3 inoculated
      mice were evenly divided into myocarditis group (n=32), carvedilol group (n=32)
      and metoprolol group (n=32). Twenty mice (control group) were inoculated
      intraperitoneally with normal saline. Hematoxylin and eosin staining and
      histopathologic scoring were used to investigate the effects of carvedilol and
      metoprolol on myocardial histopathologic changes on days 3 and 5. In addition,
      serum cTn-I levels, cytokine levels and virus titers were determined using
      chemiluminescence immunoassay, enzyme-linked immunosorbent assay and plaque
      assay, respectively, on days 3 and 5. Finally, the levels of phosphorylated
      p38MAPK were studied using immunohistochemical staining and Western blotting on
      day 5. RESULTS: Carvedilol had a stronger effect than metoprolol in reducing the
      pathological scores of VMC induced by CVB3. Both carvedilol and metoprolol
      reduced the levels of cTn-I, but the effect of carvedilol was stronger.
      Carvedilol and metoprolol decreased the levels of myocardial pro-inflammatory
      cytokines and increased the expression of anti-inflammatory cytokine, with the
      effects of carvedilol being stronger than those of metoprolol. Carvedilol had a
      stronger effect in reducing myocardial virus concentration compared with
      metoprolol. Carvedilol was stronger than metoprolol in decreasing the levels of
      myocardial phosphorylated p38MAPK. CONCLUSIONS: In conclusion, carvedilol was
      more potent than metoprolol in ameliorating myocardial lesions in VMC, probably
      due to its stronger modulation of the balance between pro- and anti-inflammatory
      cytokines by inhibiting the activation of p38MAPK pathway through beta1- and
      beta2-adrenoreceptors.

PMID- 24905655
TI  - Multiparametric magnetic resonance imaging (MRI) and active surveillance for
      prostate cancer: future directions.

PMID- 24905656
TI  - Squamous cell carcinoma of the penis: therapeutic targeting of the epidermal
      growth factor receptor.

PMID- 24905657
TI  - Early stent removal after pyeloplasty.

PMID- 24905658
TI  - Mirabegron the first beta3-adrenoceptor agonist for overactive bladder (OAB): a
      summary of the phase III studies.

PMID- 24905659
TI  - Know your nomograms.

PMID- 24905660
TI  - Peptides derived from the transmembrane domain of Bcl-2 proteins as potential
      mitochondrial priming tools.
AB  - The Bcl-2 family of proteins is crucial for apoptosis regulation. Members of this
      family insert through a specific C-terminal anchoring transmembrane domain (TMD)
      in the mitochondrial outer membrane where they hierarchically interact to
      determine cell fate. While the mitochondrial membrane has been proposed to
      actively participate in these protein-protein interactions, the influence of the
      TMD in the membrane-mediated interaction is poorly understood. Synthetic peptides
      (TMD-pepts) corresponding to the putative TMD of antiapoptotic (Bcl-2, Bcl-xL,
      Bcl-w, and Mcl-1) and pro-apoptotic (Bax, Bak) members were synthesized and
      characterized. TMD-pepts bound more efficiently to mitochondria-like bilayers
      than to plasma membrane-like bilayers, and higher binding correlated with greater
      membrane perturbation. The Bcl-2 TMD peptides promoted mitochondrial outer
      membrane permeabilization (MOMP) and cytochrome c release from isolated
      mitochondria and different cell lines. TMD-pepts exhibited nonapoptotic pro-death
      activity when apoptosis stimuli were absent. In addition, the peptides enhanced
      the apoptotic pathway induced by chemotherapeutic agents in cotreatment. Overall,
      the membrane perturbation effects of the TMD-pepts observed in the present study
      open the way for their use as new chemical tools to sensitize tumor cells to
      chemotherapeutic agents, in accordance with the concept of mitochondria priming. 

PMID- 24905661
TI  - Perfluoroalkyl chemicals and asthma among children 12-19 years of age: NHANES
      (1999-2008).
AB  - BACKGROUND: Perfluoroalkyl chemicals (PFCs) are a family of commonly used
      industrial chemicals whose persistence and ubiquity in human blood samples has
      led to concern about possible toxicity. Several animal studies and one recent
      human study have suggested a link between exposure to PFCs and asthma, although
      few epidemiologic studies have been conducted. OBJECTIVES: We investigated
      children's PFC serum concentrations and their associations with asthma-related
      outcomes. METHODS: We evaluated the association between serum concentrations of
      eight PFCs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic
      acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid
      (PFHxS), with self-reported lifetime asthma, recent wheezing, and current asthma
      using data from participants 12-19 years of age from the 1999-2000 and 2003-2008
      National Health and Nutrition Examination Surveys. RESULTS: In multivariable
      adjusted models, PFOA was associated with higher odds of ever having received a
      diagnosis of asthma [odds ratio (OR) = 1.18; 95% CI: 1.01, 1.39 for a doubling in
      PFOA], whereas for PFOS there were inverse relationships with both asthma and
      wheezing (OR = 0.88; 95% CI: 0.74, 1.04, and OR = 0.83; 95% CI: 0.67, 1.02,
      respectively). The associations were attenuated after accounting for sampling
      weights. No associations were seen between the other PFCs and any outcome.
      CONCLUSIONS: This cross-sectional study provides some evidence for associations
      between exposure to PFCs and asthma-related outcomes in children. The evidence is
      inconsistent, however, and prospective studies are needed.

PMID- 24905662
TI  - The prevalence of clinical features associated with primary ciliary dyskinesia in
      a heterotaxy population: results of a web-based survey.
AB  - Primary ciliary dyskinesia and heterotaxy are rare but not mutually exclusive
      disorders, which result from cilia dysfunction. Heterotaxy occurs in at least
      12.1% of primary ciliary dyskinesia patients, but the prevalence of primary
      ciliary dyskinesia within the heterotaxy population is unknown. We designed and
      distributed a web-based survey to members of an international heterotaxy
      organisation to determine the prevalence of respiratory features that are common
      in primary ciliary dyskinesia and that might suggest the possibility of primary
      ciliary dyskinesia. A total of 49 members (25%) responded, and 37% of the
      respondents have features suggesting the possibility of primary ciliary
      dyskinesia, defined as (1) the presence of at least two chronic respiratory
      symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting
      primary ciliary dyskinesia. Of the respondents, four completed comprehensive, in
      person evaluations, with definitive primary ciliary dyskinesia confirmed in one
      individual, and probable primary ciliary dyskinesia identified in two others. The
      high prevalence of respiratory features compatible with primary ciliary
      dyskinesia in this heterotaxy population suggests that a subset of heterotaxy
      patients have dysfunction of respiratory, as well as embryonic nodal cilia. To
      better assess the possibility of primary ciliary dyskinesia, heterotaxy patients
      with chronic oto-sino-respiratory symptoms should be referred for a primary
      ciliary dyskinesia evaluation. 

PMID- 24905663
TI  - Regulation of microRNA-155 in endothelial inflammation by targeting nuclear
      factor (NF)-kappaB P65.
AB  - Increasing evidences have illuminated the fundamental role of inflammation in
      mediating all stages of atherosclerosis. miR-155, a typical multi-functional
      miRNA, has recently emerged as a novel component of inflammatory signal
      transduction in the pathogenesis of atherosclerosis. However, little is known
      about whether endothelial highly expressed miR-155 can regulate endothelial
      inflammation-related transcription factors and the predicted role of miR-155 as a
      negative feedback regulator in endothelial inflammation involved in
      atherosclerosis. Bioinformatics analysis showed that RELA (nuclear factor-kappaB
      p65) is a potential target gene of miR-155 and this was confirmed by a luciferase
      reporter assay. Our results show that microRNA-155 mediate endothelial
      inflammation and decrease NFkB p65 and adhesion molecule expression in TNFalpha
      stimulated endothelial cells. Transfection with miR-155 significantly inhibited
      TNFalpha-induced monocyte adhesion to endothelium. Inhibition of miR-155 enhanced
      p65 level and endothelial inflammatory response which was counteracted through
      the depletion of P65 by Si-P65. On the other hand, knockdown of eNOS, another
      target of miR-155, while transfecting with miR-155 inhibitor resulted in more
      significant inflammatory response. miR-155 is highly expressed in TNFalpha
      treated HUVECs, deprived of endogenous p65 could reverse TNFalpha-induced
      upregulation of miR-155. Thus, TNFalpha induced miR-155 may serve as a negative
      feedback regulator in endothelial inflammation involved in atherosclerosis by
      targeting nuclear transcription factor P65. These results provide a rationale for
      intervention of intracellular microRNA as possible anti-atherosclerotic targets.

PMID- 24905664
TI  - A novel domino synthesis of quinazolinediones by palladium-catalyzed double
      carbonylation.
AB  - Combining commercially available bromoanilines and bromobenzonitriles in a novel
      double carbonylation process allows for a straightforward synthesis of
      isoindolo[1,2-b]quinazoline-10,12-diones. At least five different C?C and/or C?N
      bonds are selectively formed in this 3-component reaction, which likely proceeds
      through sequential carbonylation-cyclization-isomerisation-carbonylation steps.
      Notably, two molecules of CO are inserted in this highly efficient palladium
      catalyzed process. 

PMID- 24905665
TI  - MitraClip for severe symptomatic mitral regurgitation in patients at high
      surgical risk: a comprehensive systematic review.
AB  - BACKGROUND: The optimal treatment of patients with severe mitral regurgitation
      (MR) at high surgical risk (HSR) is unknown. Recently, the EVEREST II
      (Endovascular Valve Edge-to-Edge Repair) High Risk Study suggested MitraClip (MC)
      was a safe and effective treatment option. METHODS: We performed a search
      strategy for MC or mitral valve surgery (MVS) in patients at HSR for surgical
      mortality (logistic EuroSCORE >18 or STS score > 10) using Medline databases,
      proceedings of international meetings, and the STS database. We identified 21
      studies utilizing MC (n = 3,198) and MVS (n = 3,265, >90% from the STS database)
      from 2003 to 2013. Information about patient characteristics, surgical risk, and
      30-day and 1-year outcomes were extracted. RESULTS: Patients who underwent MC or
      MVS had a mean age of 74 +/- 10 years with no differences in surgical risk, NYHA
      class, or MR grade (P = 0.46). Technical success was achieved in 96% of patients
      undergoing MC versus 98% in the MVS group (P = 0.45). Patients undergoing MC were
      treated with one or two MC in 90% (n = 2,878) with only a few requiring repeat MC
      (0.4%, n = 13) or mitral surgery (0.3%, n = 52) at 30 days. The pooled event
      rates for mortality was 3.2% (95% CI [2.5-4.2]), stroke was 1.1% (95% CI [0.7
      0.2]) at 30 days. At 31 days to 1 year, the pooled event rate for mortality was
      13.0% [95% CI (9-18.3)], stroke was 1.6% [95% CI (0.8-3.2)], and repeat MVS was
      1.3% [95% CI (0.7-2.6)] with the majority of patients in the mild/moderate MR
      grade and NYHA class after MC. The 30-day event rates for mortality and stroke
      were 16.8% (95% CI [14-19]) and 4.5% (95% CI [3.9-5.3]) after MVS, respectively.
      CONCLUSION: Based on high risk MC studies and high risk MVS data predominantly
      from STS database, patients with severe MR who are at HSR can be effectively
      treated with MC or MVS. MC can be safely implanted in high risk patients with
      relatively low mortality and stroke risk.

PMID- 24905667
TI  - Toward the design of smart delivery systems controlled by integrated enzyme-based
      biocomputing ensembles.
AB  - We report herein the design of a smart delivery system in which cargo delivery
      from capped mesoporous silica (MS) nanoparticles is controlled by an integrated
      enzyme-based "control unit". The system consists of Janus-type nanoparticles
      having opposing Au and MS faces, functionalized with a pH-responsive beta
      cyclodextrin-based supramolecular nanovalve on the MS surface and two effectors,
      glucose oxidase and esterase, immobilized on the Au face. The nanodevice behaves
      as an enzymatic logical OR operator which is selectively fueled by the presence
      of D-glucose and ethyl butyrate.

PMID- 24905666
TI  - Jump-landing mechanics after anterior cruciate ligament reconstruction: a landing
      error scoring system study.
AB  - CONTEXT: The Landing Error Scoring System (LESS) is a clinical evaluation of jump
      landing mechanics and may provide useful information in assisting with return-to
      sport decisions in patients after anterior cruciate ligament reconstruction
      (ACLR). However, it is currently unknown how patients with ACLR perform on the
      LESS compared with healthy controls. OBJECTIVE: To determine if the total LESS
      score differed between individuals with ACLR and healthy controls and to
      determine the types of errors that differ between groups. DESIGN: Cross-sectional
      study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of
      27 individuals with unilateral ACLR (age = 19.8 +/- 1.8 years, height = 170 +/-
      5.5 cm, mass = 68.8 +/- 11.9 kg) and 27 controls (age = 20.5 +/- 1.7 years,
      height = 169 +/- 8.4 cm, mass = 66.6 +/- 9.0 kg) with no history of ACLR.
      INTERVENTION(S): Each participant completed 3 trials of a standardized jump
      landing task. MAIN OUTCOME MEASURE(S): Each jump landing was assessed for
      specific postures using standardized LESS criteria by a blinded evaluator.
      Individual LESS items were summed to create a total LESS score. The dominant limb
      was assessed in the control group, and the reconstructed limb was assessed in the
      ACLR group. RESULTS: The ACLR group had higher LESS scores compared with controls
      (ACLR: 6.7 +/- 2.1 errors, control: 5.6 +/- 1.5 errors, P = .04). Additionally,
      the ACLR group was more likely to err when landing with lateral trunk flexion
      (Fisher exact test, P = .002). CONCLUSIONS: Individuals with ACLR had worse
      landing mechanics as measured by the LESS. Lateral trunk deviation may be related
      to quadriceps avoidance in the reconstructed limb or poor trunk neuromuscular
      control. The LESS is useful for evaluating landing errors in patients with ACLR
      and may help to identify areas of focus during rehabilitation and before return
      to sport.

PMID- 24905669
TI  - Effect of ITO surface modification on the OLED device lifetime.
AB  - Pretreatment of the indium tin oxide (ITO) surface is generally adopted to
      improve the charge injection and device performance in the fabrication of organic
      light-emitting diodes (OLEDs). For the common approaches of surface treatment,
      such as oxygen plasma treatment, self-assembled monolayer (SAM) adsorption, and
      the PEDOT:PSS coating, different effects on the device lifetime were observed. A
      distinctly different driving voltage change with device operation time was
      obtained and was correlated with the device lifetime. The fast increase in
      driving voltage for devices based on oxygen-plasma-treated ITO is attributed to
      the work function change as a result of the change in the composition of the
      interface with device operation, whereas a rather stable work function for SAM
      modified ITO is suggested due to the permanent dipoles associated with the
      monolayer and the protecting effect of the covalently bound monolayer on the
      surface composition. 

PMID- 24905670
TI  - Research on gender differences in deployment stress and postdeployment mental
      health: addressing conceptual and methodological challenges and expanding our
      research agenda.

PMID- 24905668
TI  - Exploring consumer opinions on the presentation of side-effects information in
      Australian Consumer Medicine Information leaflets.
AB  - BACKGROUND: Consumer Medicine Information (CMI) is a brand-specific and
      standardized source of written medicine information available in Australia for
      all prescription medicines. Side-effect information is poorly presented in CMI
      and may not adequately address consumer information needs. OBJECTIVE: To explore
      consumer opinions on (i) the presentation of side-effect information in existing
      Australian CMI leaflets and alternative study-designed CMIs and (ii) side-effect
      risk information and its impact on treatment decision making. DESIGN: Fuzzy
      trace, affect heuristic, frequency hypothesis and cognitive-experiential theories
      were applied when revising existing CMI side-effects sections. Together with good
      information design, functional linguistics and medicine information expertise,
      alternative ramipril and clopidogrel CMI versions were proposed. Focus groups
      were then conducted to address the study objectives. PARTICIPANTS AND SETTING:
      Three focus groups (n = 18) were conducted in Sydney, Australia. Mean consumer
      age was 58 years (range 50-65 years), with equal number of males and females.
      RESULTS: All consumers preferred the alternative CMIs developed as part of the
      study, with unequivocal preference for the side-effects presented in a simple
      tabular format, as it allowed quick and easy access to information. Consumer
      misunderstandings reflected literacy and numeracy issues inherent in consumer
      risk appraisal. Many preferred no numerical information and a large proportion
      preferred natural frequencies. CONCLUSIONS: One single method of risk
      presentation in CMI is unable to cater for all consumers. Consumer
      misunderstandings are indicative of possible health literacy and numeracy factors
      that influence consumer risk appraisal, which should be explored further.

PMID- 24905671
TI  - Estrogen-negative feedback and estrous cyclicity are critically dependent upon
      estrogen receptor-alpha expression in the arcuate nucleus of adult female mice.
AB  - The location and characteristics of cells within the brain that suppress GnRH
      neuron activity to contribute to the estrogen-negative feedback mechanism are
      poorly understood. Using adeno-associated virus (AAV)-mediated Cre-LoxP
      recombination in estrogen receptor-alpha (ERalpha) floxed mice
      (ERalpha(flox/flox)), we aimed to examine the role of ERalpha-expressing neurons
      located in the arcuate nucleus (ARN) in the estrogen-negative feedback mechanism.
      Bilateral injection of AAV-Cre into the ARN of ERalpha(flox/flox) mice (n = 14)
      resulted in the time-dependent ablation of up to 99% of ERalpha-immunoreactive
      cell numbers throughout the rostrocaudal length of the ARN. These mice were all
      acyclic by 5 weeks after AAV-Cre injections with most mice in constant estrous.
      Control wild-type mice injected with AAV-Cre (n = 13) were normal. Body weight
      was not altered in ERalpha(flox/flox) mice. After ovariectomy, a significant
      increment in LH secretion was observed in all genotypes, although its magnitude
      was reduced in ERalpha(flox/flox) mice. Acute and chronic estrogen-negative
      feedback were assessed by administering 17beta-estradiol to mice as a bolus (LH
      measured 3 h later) or SILASTIC brand capsule implant (LH measured 5 d later).
      This demonstrated that chronic estrogen feedback was absent in ERalpha(flox/flox)
      mice, whereas the acute feedback was normal. These results reveal a critical role
      for ERalpha-expressing cells within the ARN in both estrous cyclicity and the
      chronic estrogen negative feedback mechanism in female mice. This suggests that
      ARN cells provide a key indirect, transsynpatic route through which estradiol
      suppresses the activity of GnRH neurons. 

PMID- 24905673
TI  - Intima-Media Thickness in 11- to 13-Year-Old Children: Variation Attributed to
      Sedentary Behavior, Physical Activity, Cardiorespiratory Fitness, and Waist
      Circumference.
AB  - BACKGROUND: It is unclear how sedentary behavior (SED), physical activity (PA),
      and cardiorespiratory fitness (CRF) influence vascular structure in children of
      varying body size. This study examined whether associations between SED, PA, and
      CRF with intima-media thickness (IMT) added to that of abdominal fatness and IMT.
      Differences in physiological measures among waist circumference (WC) percentiles
      were tested. METHODS: We assessed IMT of the carotid artery in 265 children aged
      11 to 13 years (135 girls). Measures included IMT assessed with high-resolution
      ultrasonography, WC, body fat mass (BFM) from DXA, and CRF determined using a
      maximal cycle test. SED and PA were assessed by accelerometry. Association
      between IMT and CRF adjusted for PA variables, and body composition phenotypes
      were tested with multiple linear regression analysis. RESULTS: CRF was related to
      IMT independently of moderate to vigorous PA (MVPA) and SED (P < .05). When WC
      was added to the model CRF was no longer associated with IMT (P > .05). Children
      in the higher WC group had increased mean values of BMI, BFM, WC, and IMT and
      lower MVPA and CRF (P < .05). CONCLUSION: Full modeling of SED, MVPA, CRF, and WC
      revealed that regional adiposity appears to have the biggest role in arterial
      structure of children.

PMID- 24905674
TI  - Self-assembly of lipopolysaccharide layers on allantoin crystals.
AB  - Self-assembly of lipopolysaccharides (LPS) on solid surfaces is important for the
      study of bacterial membranes, but has not been possible due to technical
      difficulties and the lack of suitable solid supports. Recently we found that
      crystals of the natural compound allantoin selectively bind pure LPS with sub
      nanomolar affinity. The physicochemical origins of this selectivity and the
      adsorption mode of LPS on allantoin crystals remain, however, unknown. In this
      study we present evidence that LPS adsorption on allantoin crystals is initiated
      through hydrogen-bond attachment of hydrophilic LPS regions. Hydrophobic
      interactions between alkyl chains of adjacently adsorbed LPS molecules
      subsequently promote self-assembly of LPS layers. The essential role of hydrogen
      bond interactions is corroborated by our finding that allantoin crystals bind to
      practically any hydrophilic surface chemistry. Binding contributions of
      hydrophobic interactions between LPS alkyl chains are evidenced by the
      endothermic nature of the adsorption process and explain why the binding affinity
      for LPS is several orders of magnitude higher than for proteins (lysozyme, BSA
      and IgG) and polysaccharides. Self-assembly of LPS layers via hydrogen-bond
      attachment on allantoin crystals emerges as a novel binding mechanism and could
      be considered as a practical method for preparing biomimetic membranes on a solid
      support. 

PMID- 24905675
TI  - Surface plasmon resonance biosensor for label-free and highly sensitive detection
      of point mutation using polymerization extension reaction.
AB  - A novel biosensing technique was developed for label-free and highly sensitive
      detection of point mutation using surface plasmon resonance (SPR) biosensor
      coupled with polymerization extension reaction. In this work, 3'-thiolated DNA
      probes with complementary sequences to target DNA were immobilized onto the
      sensor surface via molecular self-assembly. In the presence of wild target
      sequences, the primers can be selectively extended by DNA polymerase to form
      double-stranded DNA. In contrast, mutant target sequences, containing one
      mutation site mismatched with the 3'-end base of the primer, cannot be elongated.
      Thus, the extension reaction products can hybridize with the capture probes
      modified on the sensor surface to induce an SPR signal. The experimental results
      showed that the presented approach could detect the mutant sequences in BRCA1
      gene related to inherited breast cancer, and the wild-type and mutant-type
      sequences were successfully discriminated. Using synthetic DNA sequences as
      targets, 100pM detection limits were achieved under the optimal reaction
      conditions. Hence, this highly sensitive and specific assay might have the
      potential to become an efficient alternative technique for point mutation
      detection in biomedical research and clinical diagnosis. 

PMID- 24905676
TI  - The study of zinc ions binding to casein.
AB  - The presented research was focused on physicochemical study of casein properties
      and the kinetics of zinc ions binding to the protein. Moreover, a fast and simple
      method of casein extraction from cow's milk has been proposed. Casein isoforms,
      zeta potential (zeta) and particle size of the separated caseins were
      characterized with the use of capillary electrophoresis, zeta potential analysis
      and field flow fractionation (FFF) technique, respectively. The kinetics of the
      metal-binding process was investigated in batch adsorption experiments.
      Intraparticle diffusion model, first-order and zero-order kinetic models were
      applied to test the kinetic experimental data. Analysis of changes in infrared
      bands registered for casein before and after zinc binding was also performed. The
      obtained results showed that the kinetic process of zinc binding to casein is not
      homogeneous but is expressed with an initial rapid stage with about 70% of zinc
      ions immobilized by casein and with a much slower second step. Maximum amount of
      bound zinc in the experimental conditions was 30.04mgZn/g casein. 

PMID- 24905677
TI  - In vitro degradability, bioactivity and cell responses to mesoporous magnesium
      silicate for the induction of bone regeneration.
AB  - Mesoporous magnesium silicate (m-MS) was synthesized, and the in vitro
      degradability, bioactivity and primary cell responses to m-MS were investigated.
      The results suggested that the m-MS with mesoporous channels of approximately 5nm
      possessed the high specific surface area of 451.0m(2)/g and a large specific pore
      volume of 0.41cm(3)/g compared with magnesium silicate (MS) without mesopores of
      75m(2)/g and 0.21cm(3)/g, respectively. The m-MS was able to absorb a large
      number of water, with water absorption of 74% compared with 26% for MS. The m-MS
      was also degradable in a Tris-HCl solution, with a weight loss ratio of 40wt%
      after a 70-day immersion period. The m-MS exhibited good in vitro bioactivity,
      inducing apatite formation on its surfaces after soaking in simulated body fluid
      (SBF) at a faster rate than observed for MS. The m-MS surface clearly promoted
      the proliferation and differentiation of MC3T3-E1 cells, and their normal cell
      morphology indicated excellent cytocompatibility. This study suggested that
      mesoporous magnesium silicate with a high specific surface area and pore volume
      had suitable degradability and good bioactivity and biocompatibility, making it
      an excellent candidate biomaterial for the induction of bone regeneration. 

PMID- 24905678
TI  - Fabrication of cell penetration enhanced poly (l-lactic acid-co-E
      caprolactone)/silk vascular scaffolds utilizing air-impedance electrospinning.
AB  - In the vascular prosthetic field, the prevailing thought is that for clinical,
      long-term success, especially bioresorbable grafts, cellular migration and
      penetration into the prosthetic structure is required to promote neointima
      formation and vascular wall development. In this study, we fabricated poly (l
      lactic acid-co-E-caprolactone) P(LLA-CL)/silk fibroin (SF) vascular scaffolds
      through electrospinning using both perforated mandrel subjected to various
      intraluminal air pressures (0-300kPa), and solid mandrel. The scaffolds were
      evaluated the cellular infiltration in vitro and mechanical properties. Vascular
      scaffolds were seeded with smooth muscle cells (SMCs) to evaluate cellular
      infiltration at 1, 7, and 14 days. The results revealed that air-impedance
      scaffolds allowed significantly more cell infiltration as compared to the
      scaffolds fabricated with solid mandrel. Meanwhile, results showed that both
      mandrel model and applied air pressure determined the interfiber distance and the
      alignment of fibers in the enhanced porosity regions of the structure which
      influenced cell infiltration. Uniaxial tensile testing indicated that the air
      impedance scaffolds have sufficient ultimate strength, suture retention strength,
      and burst pressure as well as compliance approximating a native artery. In
      conclusion, the air-impedance scaffolds improved cellular infiltration without
      compromising overall biomechanical properties. These results support the
      scaffold's potential for vascular grafting and in situ regeneration. 

PMID- 24905679
TI  - Preparation of transparent zein films for cell culture applications.
AB  - In our previous studies, zein has shown good cell compatibility in both films and
      porous scaffolds. To use the zein film in microfluidic devices or as a cell
      culture substrate, swelling and excessive degradation should be avoided.
      Moreover, the film should be transparent. In this study, we found that the zein
      film could maintain good transparency even after swelling when it was treated for
      20min at 121 degrees C, 100% relative humidity and 103.4kPa, especially for the
      zein film without the addition of a plasticizer. FT-IR and XRD analysis showed
      that the ratio of alpha-helix of zein structure decreased and the ratio of its
      beta-sheet increased. Proliferation of NIH 3T3 cells on the transparent zein film
      was as cytocompatible as the untreated one and the cell culture plate. The
      improved transparency of zein films after swelling will expand the application
      field of zein. 

PMID- 24905680
TI  - The effect of soy protein structural modification on emulsion properties and
      oxidative stability of fish oil microcapsules.
AB  - Hydrolysates of soy protein isolate-maltodextrin (SPI-Md) conjugate were used as
      wall material to prepare fish oil microcapsules by freeze-drying method. Effects
      of the protein structural modifications on the physicochemical properties of the
      emulsion and the oxidative stability of the microcapsules were characterized.
      Compared with emulsions of SPI-Md conjugates or soy protein isolate/maltodextrin
      (SPI/Md) mixture, lower droplet size (212.5-329.3nm) and polydispersity index
      (PDI) (0.091-0.193) were obtained in the fish oil emulsions prepared by SPI-Md
      conjugate hydrolysates. The improved amphiphilic property of SPI-Md conjugate
      hydrolysates was supported by the results of surface and interfacial tension, and
      further confirmed by the improved emulsion stability during the storage period.
      Although the microencapsulation efficiency (MEE) of SPI-Md conjugate hydrolysates
      slightly decreased from 97.84% to 91.47% with the increasing degree of hydrolysis
      (DH), their oxidative stabilities (peroxide value and headspace propanal) were
      apparently improved compared with native SPI/Md mixture or SPI-Md conjugates
      system. Moreover, favorable thermal stability as well as a porous and uniform
      surface structure of the microcapsules coated by SPI-Md conjugate hydrolysates
      (DH 2.9%) was observed via the thermal analysis and scanning electron microscope
      (SEM) micrographs, respectively. 

PMID- 24905682
TI  - Latex-protein complexes from an acute phase recombinant antigen of Toxoplasma
      gondii for the diagnosis of recently acquired toxoplasmosis.
AB  - The synthesis and characterization of latex-protein complexes (LPC), from the
      acute phase recombinant antigen P35 (P35Ag) of Toxoplasma gondii and "core-shell"
      carboxylated or polystyrene (PS) latexes (of different sizes and charge
      densities) are considered, with the aim of producing immunoagglutination reagents
      able to detect recently acquired toxoplasmosis. Physical adsorption (PA) and
      chemical coupling (CC) of P35Ag onto latex particles at different pH were
      investigated. Greater amounts of adsorbed protein were obtained on PS latexes
      than on carboxylated latexes, indicating that hydrophobic forces govern the
      interactions between the protein and the particle surface. In the CC experiments,
      the highest amount of bound protein was obtained at pH 6, near the isoelectric
      point of the protein (IP=6.27). At this pH, it decreased both the repulsion
      between particle surface and protein, and the repulsion between neighboring
      molecules. The LPC were characterized and the antigenicity of the P35Ag protein
      coupled on the particles surface was evaluated by Enzyme-Linked ImmunoSorbent
      Assay (ELISA). Results from ELISA showed that the P35Ag coupled to the latex
      particles surface was not affected during the particles sensitization by PA and
      CC and the produced LPC were able to recognize specific anti-P35Ag antibodies
      present in the acute phase of the disease. 

PMID- 24905681
TI  - Binding interactions of bacterial lipopolysaccharide and the cationic amphiphilic
      peptides polymyxin B and WLBU2.
AB  - Passage of blood through a sorbent device for removal of bacteria and endotoxin
      by specific binding with immobilized, membrane-active, bactericidal peptides
      holds promise for treating severe blood infections. Peptide insertion in the
      target membrane and rapid/strong binding is desirable, while membrane disruption
      and release of degradation products to the circulating blood is not. Here we
      describe interactions between bacterial endotoxin (lipopolysaccharide, LPS) and
      the membrane-active, bactericidal peptides WLBU2 and polymyxin B (PmB). Analysis
      of the interfacial behavior of mixtures of LPS and peptide using air-water
      interfacial tensiometry and optical waveguide lightmode spectroscopy strongly
      suggests insertion of intact LPS vesicles by the peptide WLBU2 without vesicle
      destabilization. In contrast, dynamic light scattering (DLS) studies show that
      LPS vesicles appear to undergo peptide-induced destabilization in the presence of
      PmB. Circular dichroism spectra further confirm that WLBU2, which shows
      disordered structure in aqueous solution and substantially helical structure in
      membrane-mimetic environments, is stably located within the LPS membrane in
      peptide-vesicle mixtures. We therefore expect that presentation of WLBU2 at an
      interface, if tethered in a fashion which preserves its mobility and solvent
      accessibility, will enable the capture of bacteria and endotoxin without
      promoting reintroduction of endotoxin to the circulating blood, thus minimizing
      adverse clinical outcomes. On the other hand, our results suggest no such
      favorable outcome of LPS interactions with polymyxin B. 

PMID- 24905683
TI  - Nanomechanical properties of poly(l-lactide) nanofibers after deformation.
AB  - Atomic force microscopy (AFM) technique was used to investigate the
      nanomechanical properties of poly(l-lactide) (PLLA) nanofibers produced by the
      thermally induced phase separation (TIPS) method. Firstly, AFM-based
      nanolithography was employed to produce localized deformations on the surface of
      single PLLA nanofiber, in which the AFM tip served as a nanoscale burin to draw a
      scratch longitudinally along the nanofiber. Secondly, the morphology and physical
      properties of the nanofiber before and immediately after the deformation were
      characterized with AFM and force spectroscopy measurement. During the initial
      stage of TIPS process, the crystallization of PLLA resulted in a regular
      arrangement of crystalline domains along the thinner fibrils which then assembled
      laterally into larger nanofibers. The deformation due to the nanoindentation and
      plowing with the probe induced structural variation of PLLA nanofibers and led to
      a functional consequence in their nanomechanical properties. The region after
      deformation had a higher adhesion force and elastic modulus, probably because the
      polymer chains became more compact and ordered under both compression and shear
      stresses. 

PMID- 24905684
TI  - Molecular engineering of avidin and hydrophobin for functional self-assembling
      interfaces.
AB  - Control over the functionality of interfaces through biomolecular engineering is
      a central tool for nanoscale technology as well as many current applications of
      biology. In this work we designed fusion proteins that combined the surface
      adhesion and interfacial activity of a hydrophobin-protein together with the high
      affinity biotin-binding capability of an avidin-protein. We found that an overall
      architecture that was based on a circularly permuted version of avidin, dual
      chain avidin, and hydrophobin gave a highly functional combination. The protein
      was produced in the filamentous fungus Trichoderma reesei and was efficiently
      purified using an aqueous two-phase partitioning procedure. The surface adhesive
      properties were widely different compared to wild-type avidin. Functional
      characterization showed that the protein assembled on hydrophobic surfaces as a
      thin layer even at very low concentrations and efficiently bound a biotinylated
      compound. The work shows how the challenge of creating a fusion protein with
      proteins that form multimers can be solved by structural design and how protein
      self-assembly can be used to efficiently functionalize interfaces. 

PMID- 24905685
TI  - Lipid based nanoemulsifying resveratrol for improved physicochemical
      characteristics, in vitro cytotoxicity and in vivo antiangiogenic efficacy.
AB  - Resveratrol, a dietary non-flavonoid polyphenolic phytoalexin, has gained
      attention in cancer chemoprevention. However, poor aqueous solubility and
      cellular bioavailability has limited its therapeutic application. We formulated a
      lipid based delivery system of resveratrol with self nanoemulsifying ability.
      Several edible and safe lipids, surfactants and cosolvents were screened for
      solubilization of resevratrol. Developed formulation comprised of Acrysol K 150
      as a lipid and mixture of Labrasol and Transcutol HP as the surfactant system, as
      these components showed higher solubility. Pseudoternary phase diagram was
      constructed to identify the region of nanoemulsification. The formulations showed
      rapid emulsification with an average globule diameter; 85nm to 120nm and slight
      negative zeta potential. The nanocompositions exhibited cloud point above 55
      degrees C and were stable toward the gastrointestinal pH and thermodynamic stress
      testing. As compared to pristine resveratrol, the developed delivery system
      showed significant increase in vitro cytotoxicity in MCF-7 breast cancer cells.
      In vivo chick chorioallantoic membrane assay revealed enhanced antiangiogenic
      activity of composition with high lipid level. Briefly, lipid based
      nanoemulsifying resveratrol dramatically enhanced the anticancer and
      antiangiogenic activities, thus increasing its potential application in cancer
      chemotherapy. 

PMID- 24905686
TI  - Evidence of conformational changes in oil molecules with protein aggregation and
      conformational changes at oil-'protein solution' interface.
AB  - Time-dependent conformational changes of proteins and oil molecules at oil
      'protein solution' interface were studied using ATR (Attenuated Total Reflection)
      FTIR spectroscopic technique for the case of Bacillus subtilis extracellular
      proteins (BSEPs) and bovine serum albumin (BSA) in hexane-'protein solution'
      system. The IR spectra collected on the protein aggregate - film - formed at the
      hexane-'protein solution' interface demonstrated time-dependent conformational
      changes of the proteins through changes in the shapes and positions of the H2O
      'amide I' cross peaks and the amide II peaks as a function of time (0-90th
      minute). Hexane-protein intermolecular association in the film was evident as the
      CH stretching vibration peaks of hexane were present along with the amide peaks
      in all the spectra collected over a period of 90min. Conformational changes of
      the hexane molecules, along with that of the proteins, were observed via
      variations (broadening and red/blue shifts) in the CH stretching vibration peaks
      of the CH3 and the CH2 groups of hexane. The red/blue shifts of the CH stretching
      vibration peaks of hexane were different with BSEPs and BSA, further indicating
      that the conformational changes of hexane molecules being protein specific. As
      similar to the protein types considered here, at oil-'protein solution'
      interfaces, conformational changes of the oil molecules appear to be a regular
      phenomenon. 

PMID- 24905687
TI  - The effect of continuous popliteal sciatic nerve block on unplanned postoperative
      visits and readmissions after foot surgery--a randomised, controlled study
      comparing day-care and inpatient management.
AB  - Regional anaesthesia has been shown to have several advantages over general
      anaesthesia in reducing the need for, and hence cost of, unscheduled outpatient
      visits or readmission to hospital. However, the benefit has not been evaluated in
      a direct comparison between day-care patients and inpatients. We randomly
      allocated 120 patients undergoing unilateral foot surgery to either inpatient
      (two-day postoperative stay) or day-care management under continuous regional
      anaesthesia, and compared the impact on unscheduled postoperative outpatient
      visits, readmissions to hospital and the associated costs. The operations were
      performed under popliteal sciatic nerve block. A perineural catheter was inserted
      before surgery and removed from all patients on the third postoperative day. We
      found no significant difference in the incidence of outpatient visits (3.3% day
      care vs 5.0% inpatient, p = 0.640), readmissions (6.7% day-care vs 3.3%
      inpatient, p = 0.395) or complications between the two groups. Costs were also
      significantly lower in the day-care group (net difference ?8011 (L6684; $10 986)
      per patient, p < 0.001). We conclude that continuous regional anaesthesia allows
      foot surgery to be performed as a day-care procedure more cheaply than in
      inpatients, without an increase in clinical complications. 

PMID- 24905688
TI  - Buckling of dielectric elastomeric plates for soft, electrically active
      microfluidic pumps.
AB  - Elastic instabilities, when properly implemented within soft, mechanical
      structures, can generate advanced functionality. In this work, we use the voltage
      induced buckling of thin, flexible plates to pump fluids within a microfluidic
      channel. The soft electrodes that enable electrical actuation are compatible with
      fluids, and undergo large, reversible deformations. We quantified the onset of
      voltage-induced buckling, and measured the flow rate within the microchannel.
      This embeddable, flexible microfluidic pump will aid in the generation of new
      stand-alone microfluidic devices that require a tunable flow rate. 

PMID- 24905690
TI  - Low dose of arsenic trioxide triggers oxidative stress in zebrafish brain:
      expression of antioxidant genes.
AB  - Occurrence of arsenic in the aquatic environment of West Bengal (India),
      Bangladesh and other countries are of immediate environmental concern. In the
      present study, zebrafish (Danio rerio) was used as a model to investigate
      oxidative stress related enzyme activities and expression of antioxidant genes in
      the brain to 50ug/L arsenic trioxide for 90 days. In treated fish, generation of
      reactive oxygen species (ROS), malondialdehyde (MDA) and conjugated diene (CD)
      showed a triphasic response attaining a peak at the end of the exposure. In
      addition, a gradual increase in GSH level was noted until 60 days and at 90 days,
      a sudden fall was recorded which heightened arsenic toxicity. However, GSH level
      does not correlate well with the glutathione reductase (GR) activity. Generation
      of ROS in zebrafish brain due to As2O3 exposure was further evidenced by
      significant alteration of glutathione peroxidase (GPx) and catalase (CAT)
      activity, which converts H2O2 to water and helps in detoxication. Moreover,
      enhanced mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in
      As2O3 exposed zebrafish indicates a protective role of Nrf2. kelch-like ECH
      associated protein 1 (Keap1), a negative regulator of Nrf2, inversely correlates
      with the mRNA expression of Nrf2. As2O3 induced toxicity was also validated by
      the alteration in NRF2 and NRF2 dependent expression of proteins such as heme
      oxygenase1 (HO1) and NAD(P)H dehydrogenase quinone1 (NQO1). The mRNA expression
      of glutathione peroxidase (Gpx1), catalase (Cat), manganese superoxide dismutase
      (Mn-Sod), copper/zinc superoxide dismutase (Cu/Zn Sod) and cytochrome c oxidase1
      (Cox1) were also up regulated. The expression of uncoupling protein 2 (Ucp2), an
      important mitochondrial enzyme was also subdued in arsenic exposed zebrafish. The
      oxidative stress induced by arsenic also cause reduced mRNA expression of B-cell
      lymphoma 2 (Bcl2) present in the inner mitochondrial membrane and thereby
      indicating onset of apoptosis in treated fish. It is concluded that even a low
      dose of arsenic trioxide is toxic enough to induce significant oxidative stress
      in zebrafish brain.

PMID- 24905689
TI  - Transfer entropy reconstruction and labeling of neuronal connections from
      simulated calcium imaging.
AB  - Neuronal dynamics are fundamentally constrained by the underlying structural
      network architecture, yet much of the details of this synaptic connectivity are
      still unknown even in neuronal cultures in vitro. Here we extend a previous
      approach based on information theory, the Generalized Transfer Entropy, to the
      reconstruction of connectivity of simulated neuronal networks of both excitatory
      and inhibitory neurons. We show that, due to the model-free nature of the
      developed measure, both kinds of connections can be reliably inferred if the
      average firing rate between synchronous burst events exceeds a small minimum
      frequency. Furthermore, we suggest, based on systematic simulations, that even
      lower spontaneous inter-burst rates could be raised to meet the requirements of
      our reconstruction algorithm by applying a weak spatially homogeneous stimulation
      to the entire network. By combining multiple recordings of the same in silico
      network before and after pharmacologically blocking inhibitory synaptic
      transmission, we show then how it becomes possible to infer with high confidence
      the excitatory or inhibitory nature of each individual neuron. 

PMID- 24905691
TI  - Leaching behaviour and ecotoxicity evaluation of chars from the pyrolysis of
      forestry biomass and polymeric materials.
AB  - The main objective of this study was to assess the environmental risk of chars
      derived from the pyrolysis of mixtures of pine, plastics, and scrap tires, by
      studying their leaching potential and ecotoxicity. Relationships between chemical
      composition and ecotoxicity were established to identify contaminants responsible
      for toxicity. Since metallic contaminants were the focus of the present study, an
      EDTA washing step was applied to the chars to selectively remove metals that can
      be responsible for the observed toxicity. The results indicated that the
      introduction of biomass to the pyrolysis feedstock enhanced the acidity of chars
      and promote the mobilisation of inorganic compounds. Chars resulting from the
      pyrolysis of blends of pine and plastics did not produce ecotoxic eluates. A
      relationship between zinc concentrations in eluates and their ecotoxicity was
      found for chars obtained from mixtures with tires. A significant reduction in
      ecotoxicity was found when the chars were treated with EDTA, which was due to a
      significant reduction in zinc in chars after EDTA washing. 

PMID- 24905692
TI  - Identifying the component responsible for antagonism within ionic liquid mixtures
      using the up-to-down procedure integrated with a uniform design ray method.
AB  - Various chemicals in the environment always exist as mixtures. Toxicity
      interaction within mixtures may pose potential hazards and risks to the
      environmental safety and human health. Recent studies showed that toxicity
      interaction by ionic liquid (IL) mixtures can be related to a certain component.
      To identify the component, we developed a novel procedure integrating an up-to
      down process with the uniform design-based ray method (UDUD) and applied it into
      an IL mixture system of four 1-butyl-3-methylimidazolium ILs (simply [bmim]X)
      where X=Cl(-), Br(-), CH3OSO3(-) and CH3(CH2)7OSO3(-). It was shown that two
      mixture rays in the quaternary system exhibited significant antagonistic
      interaction. In this paper, the UDUD was first employed to design four ternary
      mixture systems. The microplate toxicity analysis was used to determine the
      toxicities of various mixtures to a freshwater photobacterium Vibrio qinghaiensis
      sp.-Q67. The concentration addition was taken as an additive reference to assess
      the toxicity interactions taking place in mixtures. The results revealed that
      some ternary mixture rays including [bmim]CH3(CH2)7OSO3 display antagonism while
      the ternary rays without [bmim]CH3(CH2)7OSO3 exhibit additivity. On these
      grounds, we again designed all binary mixtures containing [bmim]CH3(CH2)7OSO3,
      determined their toxicities and assessed toxicity interaction. The results showed
      that three binary mixture systems produce antagonism. Thus, it may be concluded
      that [bmim]CH3(CH2)7OSO3 is indeed a key component inducing mixture antagonism.

PMID- 24905693
TI  - Short term exposure to multi-walled carbon nanotubes induce oxidative stress and
      DNA damage in Xenopus laevis tadpoles.
AB  - The potential impact of Multiwalled Carbon NanoTubes (MWCNTs) was investigated on
      Xenopus laevis tadpoles exposed to 0.1, 1 and 10mg/L. Oxidative stress was
      measured in entire larvae exposed and DNA damage (Comet assay) was carried out in
      erythrocytes of circulating blood from 2h to 24h according to standardized
      recommendations. Results showed significant H2O2 production when larvae were
      exposed to 1mg/L and 10mg/L of MWCNTs after 4h and 2h of exposure, respectively.
      Antioxidant enzyme activities showed significant induction of catalase (CAT),
      glutathione reductase (GR) and superoxide dismutase (SOD) from only 2h of
      exposure to 10mg/L of MWCNTs. In presence of 1mg/L of MWCNTs, only GR and CAT
      activities were significantly induced at 4h. Enzyme activities do not follow a
      simple dose-effect relation, but the time of induction is shortened in relation
      with the tested concentration. The Comet assay results showed significant DNA
      damages with a dose dependent response. The profiles of DNA damages show
      fluctuations, in course of time, which are characteristics of oxidative stress
      response in relation with the continuous balance between damage and compensation
      process.

PMID- 24905694
TI  - Chlorination and chloramination of tetracycline antibiotics: disinfection by
      products formation and influential factors.
AB  - Formation of disinfection by-products (DBPs) from chlorination and chloramination
      of tetracycline antibiotics (TCs) was comprehensively investigated. It was
      demonstrated that a connection existed between the transformation of TCs and the
      formation of chloroform (CHCl3), carbon tetrachloride (CCl4),
      dichloroacetonitrile (DCAN) and dichloroacetone (DCAce). Factors evaluated
      included chlorine (Cl2) and chloramine(NH2Cl) dosage, reaction time, solution pH
      and disinfection modes. Increased Cl2/NH2Cl dosage and reaction time improved the
      formation of CHCl3 and DCAce. Formation of DCAN followed an increasing and then
      decreasing pattern with increasing Cl2 dosage and prolonged reaction time. pH
      affected DBPs formation differently, with CHCl3 and DCAN decreasing in
      chlorination, and having maximum concentrations at pH 7 in chloramination. The
      total concentrations of DBPs obeyed the following order:
      chlorination>chloramination>pre-chlorination (0.5h)>pre-chlorination (1h)>pre
      chlorination (2h).

PMID- 24905695
TI  - Three novel superoxide dismutase genes identified in the marine polychaete
      Perinereis nuntia and their differential responses to single and combined metal
      exposures.
AB  - To identify superoxide dismutase (SOD) genes and evaluate their usefulness as
      potential markers for monitoring metal toxicity in aquatic environment, we
      cloned, sequenced, and characterized 3 SOD genes (Cu/Zn-SOD1, Cu/Zn-SOD2, and Mn
      SOD) from the marine polychaete Perinereis nuntia. The accumulated metal contents
      and expressions of 3 SOD genes were compared after exposure to single and
      combinations of heavy metals, As, Ni, and Pb. The deduced amino acid sequences of
      the 3 SODs had evolutionary conserved domains, such as metal binding sites, and
      signature sequences. The phylogenetic analysis revealed that Cu/Zn-SOD1, Cu/Zn
      SOD2, and Mn-SOD were clustered with extracellular Cu/Zn-SOD, intracellular Cu/Zn
      SOD and mitochondrial Mn-SOD, respectively, of other species. The accumulated
      contents of Ni and Pb increased significantly in a time - dependent manner after
      exposure to both single and combination of the metals. However, the concentration
      of As did not change significantly in the exposure test. The quantitative real
      time polymerase chain reaction (PCR) array showed that the 3 SOD genes had
      differential expression patterns depending on the exposure condition. The
      expression of all SODs mRNAs was significantly elevated in response to Pb alone
      and in combination with As. The mRNA level of Cu/Zn-SOD1 was the highest after
      exposure to Pb alone, while that of Mn-SOD was remarkably enhanced after exposure
      to a combination of As and Pb. Exposure to Ni alone rapidly elevated the
      expression of Cu/Zn-SOD1 and Mn-SOD mRNA, which then gradually decreased.
      Exposure to As had no significant effect on the modulation of any of the SOD
      genes of P. nuntia. These results suggest that all SOD genes might play important
      roles in cellular protection as antioxidant enzymes against heavy metal toxicity
      via different modes of action in P. nuntia and might have the potential to act as
      indicators in an environment containing a mixture of metals. 

PMID- 24905696
TI  - Arsenate induced differential response in rice genotypes.
AB  - To study the differential response in two rice genotypes (PB1 and IR-64),
      hydroponically grown 14 days old plants were exposed to 50, 150 and 300uM As(V)
      for 24 and 96h. Accumulation of As was not significantly higher in PB1 variety
      except at higher concentration (300MUM) and duration (96h), but up regulation of
      gene transcripts were higher as compared to IR-64. Inhibition in seed
      germination, root-shoot length, chlorophyll and protein content was observed in
      both varieties with increasing concentration and exposure time. PB1 variety was
      found more capable to detoxify As(V) through induction of antioxidant defense
      system and other stress related parameters (cysteine, proline content). SDS-PAGE
      and semi quantitative RT-PCR analysis showed significant changes in protein
      profile and gene expression analysis. The results suggests that various studied
      parameters and transcripts accumulation showed a combinatorial type of tolerance
      mechanism in PB1 variety to provide better protection against As(V) stress.

PMID- 24905697
TI  - Metal, metallothionein and glutathione levels in blue crab (Callinectes sp.)
      specimens from southeastern Brazil.
AB  - Metal concentrations (Cu, Pb, Zn and Cd) were determined in muscle, gills, soft
      tissues and eggs in male, non-ovigerous and ovigerous female Callinectes sp.
      specimens from a reference site in Southeastern Brazil. Metallothionein (MT) and
      reduced glutathione (GSH) levels were also determined. Results demonstrate that
      sex has a significant influence on metal, MT and GSH concentrations. Significant
      maternal transfer of Pb and Zn from ovigerous females to eggs was verified, while
      female crabs, both ovigerous and non-ovigerous, showed elevated GSH and MT in
      viscera when compared to males, indicating possible MT role in excreting metals
      to eggs in ovigerous females of this species. Several strong statistical
      correlations between metals and MT indicate MTs role in detoxification of both
      toxic and essential elements in different organs. Pb and Zn were significantly
      correlated to GSH, indicating oxidative stress caused by the former and a direct
      link between Zn and GSH in maintaining homeostasis. Regarding human consumption,
      metal concentrations were lower than the maximum permissible levels established
      by international and Brazilian regulatory agencies, indicating that this species
      is safe for human consumption concerning this parameter. The presence of metals
      in Callinectes sp., however, is still of importance considering that this is a
      key species within the studied ecosystem and, therefore, plays a major role in
      the transference of pollutants to higher trophic levels. In addition, the
      presence of significant metal concentrations found in eggs must be considered in
      this context, since crab eggs are eaten by several other species, such as
      shorebirds, seabirds, and fish. Also, to the best of our knowledge, this is the
      first study regarding both MT and GSH levels in Callinectes sp. eggs and is of
      interest in the investigation of molecular mechanisms regarding metal exposure in
      these crustaceans. Data reported in this study support the conclusions from
      previous reports, provide mechanistic insights regarding metal exposure,
      metallothionein and oxidative stress induction in this species and also present
      novel data regarding eggs.

PMID- 24905698
TI  - Effects of combined exposure to 17alpha-ethynylestradiol and dibutyl phthalate on
      the growth and reproduction of adult male zebrafish (Danio rerio).
AB  - To evaluate the combined effects of 17alpha-ethynylestradiol (EE2) and dibutyl
      phthalate (DBP) on the growth and reproduction of male zebrafish, three-month-old
      fish were exposed to 0.005 or 0.020ug/L EE2, 100 or 500ug/L DBP or their binary
      mixtures under semi-static conditions. Investigated parameters include the
      length, weight, condition factor, vitellogenin (VTG) induction, acyl-CoA oxidase
      (AOX) protein level, histopathological alteration of testis, liver and gill, and
      reproductive capacity. After 21d exposure, no statistical difference was found
      among the weights, lengths and condition factors of different treatment groups.
      In all binary mixture groups, decreased VTG levels were detected compared to EE2
      only groups; and the AOX levels were significantly lower than DBP-only treatments
      while both chemicals can individually induce AOX synthesis. Therefore, EE2 and
      DBP may act additively on VTG and antagonistically on AOX induction in males.
      After 45d exposure, delayed gametogenesis was observed for the DBP-only groups,
      indicated by fewer spermatozoa and more spermatocytes, which was further
      aggravated with the addition of EE2. The developmental delay of testis partially
      recovered after a 30d depuration in clean water. Combined exposure also caused
      liver and gill lesions, which were not alleviated during the 30d depuration,
      suggesting a nonreversible harmful effect the same as single exposure. Mixed EE2
      and DBP were observed to impair the reproductive capability (the fecundity and
      fertilization rate) of males, while single exposure did not. Co-exposed to
      0.020ug/L EE2 and 100ug/L DBP promoted the early hatching of offspring (F1
      generation) at 48h post-fertilization (hpf), but the survival rates of the F1
      generation were similar in all treatments. Our findings indicate that the effects
      of mixed EE2 and DBP at environmentally relevant levels can be either
      antagonistic or additive relying on the specific toxicological endpoints and the
      respective doses of each chemical. 

PMID- 24905699
TI  - Plasma metabolites, ions and thyroid hormones levels, and hepatic enzymes'
      activity in Caspian roach (Rutilus rutilus caspicus) exposed to waterborne
      manganese.
AB  - To investigate the effect of waterborne manganese on plasma biochemical
      characteristics in fish, Caspian roach (Rutilus rutilus caspicus) was exposed to
      0 (control), 60 (M60), 150 (M150) and 300 (M300) mg/L water manganese for 96h.
      Thereafter, plasma biochemical characteristics were studied. Plasma glucose level
      significantly increased in M60 and decreased in M150 and M300 groups, compared to
      the control. M300 had significantly lower hematocrit compared to the control.
      Albumin remained unchanged after manganese exposure, however, the manganese
      exposed fish showed significant increase in plasma total protein levels. M150 and
      M300 showed significant increase in the plasma cholesterol and triglyceride
      levels compared to the control and M60. M60 and M150 had significantly higher
      alkaline phosphatase (ALP) activity compared to the control. The manganese
      exposed groups had significantly higher alanine aminotransferase (ALT) activity
      compared to the control. M150 and M300 had aspartate aminotransferase (AST)
      activity significantly higher than those of the control and M60. M300 had
      significantly higher triiodothyronine (T3) levels than the other groups. All
      manganese-exposed fish had significantly higher thyroxin (T4) levels than the
      control. The plasma levels of chloride showed a significant decrease in the
      manganese-exposed fish, compared to the control. M150 and M300 had significantly
      lower sodium levels, compared to the control. M60 and M150 had significantly
      lower plasma calcium levels compared to the other groups. It is concluded that
      clinical chemistry along with thyroid hormones levels can be the useful tools to
      monitor manganese toxicity in fish. The possible mechanisms involving in the
      biochemical changes were discussed.

PMID- 24905700
TI  - Protein kinase A regulates the osteogenic activity of Osterix.
AB  - Osterix belongs to the SP gene family and is a core transcription factor
      responsible for osteoblast differentiation and bone formation. Activation of
      protein kinase A (PKA), a serine/threonine kinase, is essential for controlling
      bone formation and BMP-induced osteoblast differentiation. However, the
      relationship between Osterix and PKA is still unclear. In this report, we
      investigated the precise role of the PKA pathway in regulating Osterix during
      osteoblast differentiation. We found that PKA increased the protein level of
      Osterix; PKA phosphorylated Osterix, increased protein stability, and enhanced
      the transcriptional activity of Osterix. These results suggest that Osterix is a
      novel target of PKA, and PKA modulates osteoblast differentiation partially
      through the regulation of Osterix.

PMID- 24905702
TI  - Redox chemistry and metal-insulator transitions intertwined in a nano-porous
      material.
AB  - Metal-organic frameworks are nano-porous adsorbents of relevance to gas
      separation and catalysis, and separation of oxygen from air is essential to
      diverse industrial applications. The ferrous salt of 2,5-dihydroxy-terephthalic
      acid, a metal-organic framework of the MOF74 family, can selectively adsorb
      oxygen in a manner that defies the classical picture: adsorption sites either do
      or do not share electrons over a long range. Here we propose, and then justify
      phenomenologically and computationally, a mechanism. Charge-transfer-mediated
      adsorption of electron acceptor oxygen molecules in the metal-organic framework,
      which is a quasi-one-dimensional electron-donor semiconductor, drives and is
      driven by quasi-one-dimensional metal-insulator-metal transitions that localize
      or delocalize the quasi-one-dimensional electrons. This mechanism agrees with the
      empirical evidence, and predicts a class of nano-porous semiconductors or metals
      and potential adsorbents and catalysts in which chemistry and metal-insulator
      metal transitions intertwine. 

PMID- 24905701
TI  - Genomic analysis and differential expression of HMG and S100A family in human
      arthritis: upregulated expression of chemokines, IL-8 and nitric oxide by HMGB1.
AB  - We applied global gene expression arrays, quantitative real-time PCR,
      immunostaining, and functional assays to untangle the role of High Mobility
      Groups proteins (HMGs) in human osteoarthritis (OA)-affected cartilage.
      Bioinformatics analysis showed increased mRNA expression of Damage-Associated
      Molecular Patterns (DAMPs): HMGA, HMGB, HMGN, SRY, LEF1, HMGB1, MMPs, and
      HMG/RAGE-interacting molecules (spondins and S100A4, S100A10, and S100A11) in
      human OA-affected cartilage as compared with normal cartilage. HMGB2 was down
      regulated in human OA-affected cartilage. Immunohistological staining identified
      HMGB1 in chondrocytes in the superficial cartilage. Cells of the deep cartilage
      and subchondral bone showed increased expression of HMGB1 in OA-affected
      cartilage. HMGB1 was expressed in the nucleus, cytosol, and extracellular milieu
      of chondrocytes in cartilage. Furthermore, HMGB1 was spontaneously released from
      human OA-affected cartilage in ex vivo conditions. The effects of recombinant
      HMGB1 was tested on human cartilage and chondrocytes in vitro. HMGB1 stimulated
      mRNA of 2 NFkappaB gene enhancers (NFkappaB1 and NFkappaB2), 16 CC and CXC
      chemokines (IL-8, CCL2, CCL20, CCL3, CCL3L1, CCL3L3, CCL4, CCL4L1, CCL4L2, CCL5,
      CCL8, CXCL1, CXCL10, CXCL2, CXCL3, and CXCL6) by >=10-fold. Furthermore, HMGB1
      and IL-1beta and/or tumor necrosis factor alpha (but not HMGI/Y) also
      significantly induced inducible nitric oxide synthase, NO, and interleukin (IL)-8
      production in human cartilage and chondrocytes. The recombinant HMGB1 utilized in
      this study shows properties that are similar to disulfide-HMGB1. The
      differential, stage and/or tissue-specific expression of HMGB1, HMGB2, and S100A
      in cartilage was associated with regions of pathology and/or cartilage
      homeostasis in human OA-affected cartilage. Noteworthy similarities in the
      expression of mouse and human HMGB1 and HMGB2 were conserved in normal and
      arthritis-affected cartilage. The multifunctional forms of HMGB1 and S100A could
      perpetuate damage-induced cartilage inflammation in late-stage OA-affected joints
      similar to sterile inflammation. The paracrine effects of HMGB1 can induce
      chemokines and NO that are perceived to change cartilage homeostasis in human OA
      affected cartilage. 

PMID- 24905704
TI  - A comparison of different statistical methods analyzing hypoglycemia data using
      bootstrap simulations.
AB  - Hypoglycemia has long been recognized as a major barrier to achieving
      normoglycemia with intensive diabetic therapies. It is a common safety concern
      for the diabetes patients. Therefore, it is important to apply appropriate
      statistical methods when analyzing hypoglycemia data. Here, we carried out
      bootstrap simulations to investigate the performance of the four commonly used
      statistical models (Poisson, negative binomial, analysis of covariance [ANCOVA],
      and rank ANCOVA) based on the data from a diabetes clinical trial. Zero-inflated
      Poisson (ZIP) model and zero-inflated negative binomial (ZINB) model were also
      evaluated. Simulation results showed that Poisson model inflated type I error,
      while negative binomial model was overly conservative. However, after adjusting
      for dispersion, both Poisson and negative binomial models yielded slightly
      inflated type I errors, which were close to the nominal level and reasonable
      power. Reasonable control of type I error was associated with ANCOVA model. Rank
      ANCOVA model was associated with the greatest power and with reasonable control
      of type I error. Inflated type I error was observed with ZIP and ZINB models. 

PMID- 24905705
TI  - Does need matter? Needs assessments and decision-making among major humanitarian
      health agencies.
AB  - Disasters of physical origin, including earthquakes, floods, landslides, tidal
      waves, tropical storms, tsunamis, and volcanic eruptions, have affected millions
      of people globally over the past 100 years. Proportionately, there is far greater
      likelihood of being affected by such disasters in low-income countries than in
      high-income countries. Furthermore, low-income countries are in need of
      international assistance following disasters more often than high-income
      countries. The funding of international humanitarian assistance has increased
      from USD 12.9 billion in 2006 to an estimated USD 16.7 billion in 2010. The
      majority of this funding is channelled through humanitarian agencies and is
      supposed to be distributed based on the need of those affected, as assessed using
      needs assessments. Such needs assessments may be used to inform decisions
      internally, to influence others, to justify response decisions, and to obtain
      funding. Little is known about the quality of needs assessments in practical
      applications. Consequently, this paper reports on and analyses the views of
      operational decision-makers in major health-related humanitarian agencies on
      needs assessments. 

PMID- 24905706
TI  - Attitude before method: disability in vulnerability and capacity assessment.
AB  - Many agencies working on disaster risk reduction use vulnerability and capacity
      assessment (VCA) to identify vulnerable groups, to assess their needs and
      capacities, and to develop appropriate programmes and policies. In theory, VCA
      offers a good opportunity to incorporate disabled people's needs and resources in
      counter-disaster programming. This paper seeks to establish and explain the
      extent to which disability is included in VCA in practice. It reviews VCA reports
      and findings, formal VCA guidance, and other methodological literature. The
      review indicates that disability is a neglected issue in VCA practice and that
      manuals and guidelines, while promoting the general ideal of inclusiveness, are
      insufficiently aware of the challenges to achieving this in practice and do not
      offer enough guidance on how to reach and include disabled people. Ways of
      overcoming these problems are suggested. However, the real challenge may be to
      change core attitudes and perceptions of disability within implementing
      organisations. 

PMID- 24905703
TI  - Physical Activity for Campus Employees: A University Worksite Wellness Program.
AB  - BACKGROUND: Workplaces provide ideal environments for wellness programming. The
      purpose of this study was to explore exercise self-efficacy among university
      employees and the effects of a worksite wellness program on physical activity,
      cardiorespiratory fitness, and cardiovascular disease (CVD) risk factors.
      METHODS: Participants included 121 university employees (85% female). The
      worksite wellness program included cardiovascular health assessments, personal
      health reports, 8 weeks of pedometer-based walking and tracking activities, and
      weekly wellness sessions. Daily step count was assessed at baseline, Week 4, and
      Week 8. Exercise self-efficacy and CVD risk factors were evaluated at baseline
      and follow-up. RESULTS: Daily step count increased from 6566 +/- 258 (LSM +/- SE)
      at baseline to 8605 +/- 356 at Week 4 and 9107 +/- 388 at Week 8 (P < .0001).
      Steps increased among normal weight, overweight, and obese subgroups. Exercise
      self-efficacy correlated with baseline steps (P < .05). Small improvements were
      observed in cardiorespiratory fitness, body mass index, blood pressure, blood
      glucose, total cholesterol, and triglycerides (all P < .01). CONCLUSIONS: A
      worksite wellness program was effective for improving physical activity,
      cardiorespiratory fitness, and CVD risk factors among university employees.
      Exercise barriers and outcome expectations were identified and have implications
      for future worksite wellness programming.

PMID- 24905707
TI  - The impact of a natural disaster on altruistic behaviour and crime.
AB  - Institutional altruism in the form of a public-sector intervention and support
      for victims and social altruism generated by mutual aid and solidarity among
      citizens constitute a coming together in a crisis. This coming together and
      mutual support precipitate a decrease in crime rates during such an event. This
      paper presents an analysis of daily fluctuations in crime during the prolonged
      ice storms in Quebec, Canada, in January 1998 that provoked an electrical
      blackout. Of particular interest are the principal crisis-related influences on
      daily crime patterns. A first series of analyses examines the impact of
      altruistic public-sector mobilisation on crime. A significant decline in property
      crime rates was noticed when cheques were distributed to crisis victims in
      financial need in Monteregie, and hence they were attributable to public
      intervention (institutional altruism). Moreover, the rate of social altruism
      (financial donations), which was more substantial in adjoining rather than
      distant regions, was inversely proportional to crime rates. 

PMID- 24905708
TI  - Livestock mortality in pastoralist herds in Ethiopia and implications for drought
      response.
AB  - Participatory epidemiology methods were employed retrospectively in three
      pastoralist regions of Ethiopia to estimate the specific causes of excess
      livestock mortality during drought. The results showed that
      starvation/dehydration accounted for between 61.5 and 100 per cent of excess
      livestock mortality during drought, whereas disease-related mortality accounted
      for between 0 and 28.1 per cent of excess mortality. Field observations indicate
      that, in livestock, disease risks and mortality increase in the immediate post
      drought period, during rain. The design of livelihoods-based drought response
      programmes should include protection of core livestock assets, and it should take
      account of the specific causes of excess livestock mortality during drought and
      immediately afterwards. This study shows that, when comparing livestock feed
      supplementation and veterinary support, relatively more aid should be directed at
      the former if the objective is to protect core livestock during drought.
      Veterinary support should consider disease-related mortality in the immediate
      post-drought period, and tailor inputs accordingly. 

PMID- 24905709
TI  - Conflict resilience among community forestry user groups: experiences in Nepal.
AB  - This paper explores the impact of violent conflict in Nepal on the functioning of
      community forestry user groups (CFUGs), particularly those supported by the
      Livelihoods and Forestry Programme, funded by the United Kingdom's Department for
      International Development (DFID). The key questions are: (i) what explains the
      resilience of CFUGs operating at the time of conflict?; (ii) what institutional
      arrangements and strategies allowed them to continue working under conflict
      conditions?; and (iii) what lessons can be drawn for donor-supported development
      around the world? The study contributes to other research on the everyday
      experiences of residents of Nepal living in a period of conflict. It suggests
      that CFUG resilience was the result of the institutional set up of community
      forestry and the employment of various tactics by the CFUGs. While the
      institutional design of community forestry (structure) was very important for
      resilience, it was the ability of the CFUGs to support and use it effectively
      that was the determining factor in this regard. 

PMID- 24905710
TI  - The adoption of a climate disaster resilience index in Chennai, India.
AB  - Results derived from the Climate Disaster Resilience Index (CDRI)-consisting of
      five dimensions (economic, institutional, natural, physical, and social), 25
      parameters, and 125 variables-reflect the abilities of people and institutions to
      respond to potential climate-related disasters in Chennai, India. The findings of
      this assessment, applied in the 10 administrative zones of the city, reveal that
      communities living in the northern and older parts of Chennai have lower overall
      resilience as compared to the flourishing areas (vis-a-vis economic growth and
      population) along the urban fringes. The higher resilience of communities along
      the urban fringes suggests that urbanisation may not necessarily lead to a
      deterioration of basic urban services, such as electricity, housing, and water.
      This indication is confirmed by a strong statistical correlation between physical
      resilience and population growth in Chennai. The identification of the resilience
      of different urban areas of Chennai has the potential to support future planning
      decisions on the city's scheduled expansion. 

PMID- 24905711
TI  - General overview of the disaster management framework in Cameroon.
AB  - Efficient and effective disaster management will prevent many hazardous events
      from becoming disasters. This paper constitutes the most comprehensive document
      on the natural disaster management framework of Cameroon. It reviews critically
      disaster management in Cameroon, examining the various legislative,
      institutional, and administrative frameworks that help to facilitate the process.
      Furthermore, it illuminates the vital role that disaster managers at the
      national, regional, and local level play to ease the process. Using empirical
      data, the study analyses the efficiency and effectiveness of the actions of
      disaster managers. Its findings reveal inadequate disaster management policies,
      poor coordination between disaster management institutions at the national level,
      the lack of trained disaster managers, a skewed disaster management system, and a
      top-down hierarchical structure within Cameroon's disaster management framework.
      By scrutinising the disaster management framework of the country, policy
      recommendations based on the research findings are made on the institutional and
      administrative frameworks. 

PMID- 24905712
TI  - Uniting multi-adult households during emergency evacuation planning.
AB  - When a no-notice emergency prompts an evacuation, family members in different
      locations throughout a city may unite so that they can evacuate as a group. This
      paper draws on data from more than 300 interviews conducted in the metropolitan
      area of Chicago, Illinois, United States. The study uses discrete choice models
      to analyse the expectations of respondents regarding whether their likely plans
      for evacuation involve gathering spouses, parents, adult-age children, and/or non
      family members. In addition, it addresses the matter of whether respondents plan
      to reunite with family members at home. Individuals' access to a personal car is
      the dominating factor in predicting whether respondents plan to gather a spouse.
      Being the parent of a child under the age of 18 years increases the tendency to
      report planning to reunite with family members at home. Both commute mode and car
      availability are not significantly associated with plans to reunite at home. 

PMID- 24905713
TI  - Decision-making and evacuation planning for flood risk management in the
      Netherlands.
AB  - A traditional view of decision-making for evacuation planning is that, given an
      uncertain threat, there is a deterministic way of defining the best decision. In
      other words, there is a linear relation between threat, decision, and execution
      consequences. Alternatives and the impact of uncertainties are not taken into
      account. This study considers the 'top strategic decision-making' for mass
      evacuation owing to flooding in the Netherlands. It reveals that the top
      strategic decision-making process itself is probabilistic because of the decision
      makers involved and their crisis managers (as advisers). The paper concludes that
      deterministic planning is not sufficient, and it recommends probabilistic
      planning that considers uncertainties in the decision-making process itself as
      well as other uncertainties, such as forecasts, citizens responses, and the
      capacity of infrastructure. This results in less optimistic, but more realistic,
      strategies and a need to pay attention to alternative strategies. 

PMID- 24905714
TI  - Social dimensions of science-humanitarian collaboration: lessons from Padang,
      Sumatra, Indonesia.
AB  - This paper contains a critical exploration of the social dimensions of the
      science-humanitarian relationship. Drawing on literature on the social role of
      science and on the social dimensions of humanitarian practice, it analyses a
      science-humanitarian partnership for disaster risk reduction (DRR) in Padang,
      Sumatra, Indonesia, an area threatened by tsunamigenic earthquakes. The paper
      draws on findings from case study research that was conducted between 2010 and
      2011. The case study illustrates the social processes that enabled and hindered
      collaboration between the two spheres, including the informal partnership of
      local people and scientists that led to the co-production of earthquake and
      tsunami DRR and limited organisational capacity and support in relation to
      knowledge exchange. The paper reflects on the implications of these findings for
      science-humanitarian partnering in general, and it assesses the value of using a
      social dimensions approach to understand scientific and humanitarian dialogue. 

PMID- 24905715
TI  - Cyclone shelters and their locational suitability: an empirical analysis from
      coastal Bangladesh.
AB  - Bangladesh is one of the poorest and the most disaster-prone countries in Asia;
      it is important, therefore, to know how its disaster reduction strategies are
      organised and planned. Cyclone shelters comprise a widely acceptable form of
      infrastructural support for disaster management in Bangladesh. This paper
      attempts to analyse empirically their use during cyclones in a sample study area
      along the southwest coastal belt of the country. It shows how the location of a
      cyclone shelter can determine the social power structure in coastal Bangladesh.
      The results reveal that the establishment of cyclone shelters in the studied
      communities is determined by neither a right-based nor a demand-based planning
      approach; rather, their creation is dependent on the socio-political affluence of
      local-level decision-makers. The paper goes on to demonstrate that socially
      vulnerable households (defined, for example, by income or housing conditions) are
      afforded disproportionately less access to cyclone shelters as compared to less
      socially vulnerable households. 

PMID- 24905716
TI  - Antenatal hypoxia induces programming of reduced arterial blood pressure response
      in female rat offspring: role of ovarian function.
AB  - In utero exposure to adverse environmental factors increases the risk of
      cardiovascular disease in adulthood. The present study tested the hypothesis that
      antenatal hypoxia causes a gender-dependent programming of altered arterial blood
      pressure response (BP) in adult offspring. Time-dated pregnant rats were divided
      into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation) groups. The
      experiments were conducted in adult offspring. Antenatal hypoxia caused
      intrauterine growth restriction, and resulted in a gender-dependent increase
      Angiotensin II (Ang II)-induced BP response in male offspring, but significant
      decrease in BP response in female offspring. The baroreflex sensitivity was not
      significantly altered. Consistent with the reduced blood pressure response,
      antenatal hypoxia significantly decreased Ang II-induced arterial
      vasoconstriction in female offspring. Ovariectomy had no significant effect in
      control animals, but significantly increased Ang II-induced maximal BP response
      in prenatally hypoxic animals and eliminated the difference of BP response
      between the two groups. Estrogen replacement in ovariectomized animals
      significantly decreased the BP response to angiotensin II I only in control, but
      not in hypoxic animals. The result suggests complex programming mechanisms of
      antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary
      dysfunction results in the phenotype of reduced vascular contractility and BP
      response in female adult offspring. 

PMID- 24905718
TI  - Boron-nitrogen substituted perylene obtained through photocyclisation.
AB  - A BN substituted hexabenzotriphenylene (B3N3) closes one C-C-bond upon
      irradiation with light of 280-400 nm in the presence of iodine to yield a
      phenanthrene annelated B3N3 tribenzoperylene. Upon hydrolysis a B2N2
      dibenzoperylene is obtained. 

PMID- 24905717
TI  - Exploring the electron transfer pathway in the oxidation of avermectin by
      CYP107Z13 in Streptomyces ahygroscopicus ZB01.
AB  - Streptomyces ahygroscopicus ZB01 can effectively oxidize 4"-OH of avermectin to
      form 4"-oxo-avermectin. CYP107Z13 is responsible for this site-specific oxidation
      in ZB01. In the present study, we explored the electron transfer pathway in
      oxidation of avermectin by CYP107Z13 in ZB01. A putative [3Fe-4S] ferredoxin gene
      fd68 and two possible NADH-dependent ferredoxin reductase genes fdr18 and fdr28
      were cloned from the genomic DNA of ZB01. fd68 gene disruption mutants showed no
      catalytic activity in oxidation of avermectin to form 4"-oxo-avermectin. To
      clarify whether FdR18 and FdR28 participate in the electron transfer during
      avermectin oxidation by CYP107Z13, two whole-cell biocatalytic systems were
      designed in E. coli BL21 (DE3), with one co-expressing CYP107Z13, Fd68 and FdR18
      and the other co-expressing CYP107Z13, Fd68 and FdR28. Both of the two
      biocatalytic systems were found to be able to mediate the oxidation of avermectin
      to form 4"-oxo-avermectin. Thus, we propose an electron transfer pathway NADH
      >FdR18/FdR28->Fd68->CYP107Z13 for oxidation of avermectin to form 4"-oxo
      avermectin in ZB01. 

PMID- 24905720
TI  - Assessing the impact of multiple stressors on aquatic biota: the receptor's side
      matters.
AB  - Aquatic ecosystems are confronted with multiple stress factors. Current
      approaches to assess the risk of anthropogenic stressors to aquatic ecosystems
      are developed for single stressors and determine stressor effects primarily as a
      function of stressor properties. The cumulative impact of several stressors,
      however, may differ markedly from the impact of the single stressors and can
      result in nonlinear effects and ecological surprises. To meet the challenge of
      diagnosing and predicting multiple stressor impacts, assessment strategies should
      focus on properties of the biological receptors rather than on stressor
      properties. This change of paradigm is required because (i) multiple stressors
      affect multiple biological targets at multiple organizational levels, (ii)
      biological receptors differ in their sensitivities, vulnerabilities, and response
      dynamics to the individual stressors, and (iii) biological receptors function as
      networks, so that actions of stressors at disparate sites within the network can
      lead via indirect or cascading effects, to unexpected outcomes. 

PMID- 24905721
TI  - EMG and heart rate responses decline within 5 days of daily whole-body vibration
      training with squatting.
AB  - In this study, we examined the acute effects of a 5-day daily whole-body
      vibration (WBV) training on electromyography (EMG) responses of the m. rectus
      femoris and m. gastrocnemius lateralis, heart rate (HR, continuously recorded),
      and blood lactate levels. The purpose of the study was to investigate the
      adaptation of muscle activity, heart rate and blood lactate levels during 5 days
      of daily training. Two groups of healthy male subjects performed either squat
      exercises with vibration at 20 Hz on a side alternating platform (SE+V, n = 20,
      age  = 31.9+/-7.5 yrs., height  = 178.8+/-6.2 cm, body mass  = 79.2+/-11.4 kg) or
      squat exercises alone (SE, n = 21, age  = 28.4+/-7.3 years, height  = 178.9+/-7.4
      cm, body mass  = 77.2+/-9.7 kg). On training day 1, EMG amplitudes of the m.
      rectus femoris were significantly higher (P<0.05) during SE+V than during SE.
      However, this difference was no longer statistically significant on training days
      3 and 5. The heart rate (HR) response was significantly higher (P<0.05) during
      SE+V than during SE on all training days, but showed a constant decline
      throughout the training days. On training day 1, blood lactate increased
      significantly more after SE+V than after SE (P<0.05). On the following training
      days, this difference became much smaller but remained significantly different.
      The specific physiological responses to WBV were largest on the initial training
      day and most of them declined during subsequent training days, showing a rapid
      neuromuscular and cardiovascular adaptation to the vibration stimulus. 

PMID- 24905723
TI  - Evaluation of ovarian reserve in Hashimoto's thyroiditis.
AB  - Human ovary is commonly the target of an autoimmune attack in cases of organ- or
      non-organ-specific autoimmune disorders. Hashimoto's thyroiditis (HT) is likely
      to be associated with ovarian dysfunction and diminished ovarian reserve. In this
      study, we aimed to evaluate the possible negative association between this
      significantly prevalent autoimmune disease and the ovarian reserve. Thirty-two
      premenopausal women with primary hypothyroidism, who under replacement therapy
      with thyroxine were recruited. Forty-nine healthy female subjects who had normal
      anti-thyroid antibody levels and were comparable with the HT group in terms of
      age and BMI values, comprised the control group. There was no statistically
      significant difference between the study and the control patients in terms of
      antral follicle count. Serum anti-Mullerian hormone (AMH) levels were
      significantly higher in woman with HT compared to the control group. The results
      of this study found no impairment in ovarian reserve parameters of patients with
      HT. Interestingly, the results revealed a significant increase in serum AMH
      levels of the patients with HT compared to controls. Hashimoto's thyroiditis may
      share a common etiologic linkage with polycystic ovary syndrome; therefore,
      leading to elevated serum AMH levels, which we are currently unable to define
      elaborately.

PMID- 24905724
TI  - Novel insights on the malignant transformation of endometriosis into ovarian
      carcinoma.
AB  - The malignant transformation of endometriosis is an uncommon event, which happens
      in 0.7-2.5% of the cases, and, when occurs, it usually involves the ovary. A 2 to
      3-fold higher risk of ovarian endometrioid and clear cell carcinoma has been
      reported in women with endometriosis. Pathological studies have detected a
      morphological continuum of sequential steps from normal endometriotic cyst
      epithelium to atypical endometriosis and finally to invasive carcinoma. Ovarian
      endometrioid carcinoma harbors mutations of CTNNB1 in 16-53.3%, of PTEN in 14-20%
      and of ARID1A in 30-55% of the cases. Ovarian clear cell carcinoma harbors
      mutations of PIK3CA in 20-40% and of ARID1 in 15-75% of the cases. Whereas
      estrogen receptors and progesterone receptors are quite always absent, HNF-1b is
      often over-expressed in this histotype. Atypical endometriosis and endometriosis
      related ovarian neoplasms share molecular alterations, such as PTEN mutations,
      ARID1A mutations and up-regulation of HNF-1b. Moreover, ARID1A mutations have
      been noted in clear cell tumors and contiguous atypical endometriosis, but not in
      distant endometriotic lesions. The loss of BAF250a protein expression is
      suggestive for the presence of ARID1A mutations, and represents an useful marker
      of malignant transformation of endometriosis.

PMID- 24905725
TI  - Efficacy of dienogest in the treatment of symptomatic adenomyosis: a pilot study.
AB  - Adenomyosis is a common disorder in premenopausal women that causes dysmenorrhea,
      pelvic pain and menorrhagia. Considering that adenomyosis is an estrogen
      dependent disease, the medical treatment is based on this hormone. Effective and
      well-tolerated medical treatments for symptomatic adenomyosis are needed.
      Dienogest, an oral progestin, has been extensively investigated in the treatment
      of endometriosis. In this report, we present the results on the efficacy and
      safety of dienogest in the treatment of symptomatic adenomyosis. Seventeen
      patients with symptomatic adenomyosis were included in this study, of which 15
      continued dienogest for up to 24 weeks. Dienogest significantly reduced
      adenomyosis-associated pelvic pain as well as serum CA-125 and CA19-9 levels. It
      also demonstrated a modest suppression of estradiol (>50 pg/ mL), which is
      consistent with the findings of other reports. During treatment, five patients
      experienced worsening anemia because of metrorrhagia, which is the most frequent
      adverse effect associated with dienogest. This report suggests that dienogest is
      an effective and well-tolerated therapy for symptomatic adenomyosis.

PMID- 24905722
TI  - Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral
      sclerosis.
AB  - Pharmacological activation of autophagy is becoming an attractive strategy to
      induce the selective degradation of aggregate-prone proteins. Recent evidence
      also suggests that autophagy impairment may underlie the pathogenesis of several
      neurodegenerative diseases. Mutations in the gene encoding SOD1 (superoxide
      disumutase 1) trigger familial amyotrophic lateral sclerosis (ALS), inducing its
      misfolding and aggregation and the progressive loss of motoneurons. It is still
      under debate whether autophagy has a protective or detrimental role in ALS. Here
      we evaluate the impact of BECN1/Beclin 1, an essential autophagy regulator, in
      ALS. BECN1 levels were upregulated in both cells and animals expressing mutant
      SOD1. To evaluate the impact of BECN1 to the pathogenesis of ALS in vivo, we
      generated mutant SOD1 transgenic mice heterozygous for Becn1. We observed an
      unexpected increase in life span of mutant SOD1 transgenic mice haploinsufficient
      for Becn1 compared with littermate control animals. These effects were
      accompanied by enhanced accumulation of SQSTM1/p62 and reduced levels of LC3-II,
      and an altered equilibrium between monomeric and oligomeric mutant SOD1 species
      in the spinal cord. At the molecular level, we detected an abnormal interaction
      of mutant SOD1 with the BECN1-BCL2L1 complex that may impact autophagy
      stimulation. Our data support a dual role of BECN1 in ALS and depict a complex
      scenario in terms of predicting the effects of manipulating autophagy in a
      disease context. 

PMID- 24905726
TI  - Effects of a prolonged, 72 hours, interval between mifepristone and gemeprost in
      second trimester termination of pregnancy: a retrospective analysis.
AB  - OBJECTIVE: To evaluate if the 72 hours interval between mifepristone and
      gemeprost has a similar efficacy compared to the 48 hours interval for second
      trimester termination of pregnancy STUDY DESIGN: Two-hundred and fifteen
      consecutive pregnant women, admitted to our hospital, for second trimester TOP,
      were included in this retrospective analysis. Standard protocol was followed for
      all patients. On the first day of the procedure oral mifepristone 200 mg was
      administered. After 72 (group A, n = 78) or 48 hours (group B, n = 113) women
      were admitted for administration of gemeprost 1 mg pessary as per protocol. The
      induction to abortion time was defined as the interval between the insertion of
      the first gemeprost pessary and the expulsion of the fetus. RESULTS: There are no
      significant differences in the number of pessaries in the two groups. The
      induction to abortion interval was longer in group A than in group B. Twenty-one
      women required surgical evacuation of the uterus for retained placenta or
      incomplete abortion without difference between groups. CONCLUSION: A 48-hours
      interval between mifepristone and gemeprost leads to better results than a 72
      hours interval, with a shorter abortion length and represents the elective method
      for second trimester TOP.

PMID- 24905727
TI  - Effectiveness, tolerability and acceptance of an oral estradiol/levonorgestrel
      formulation for the treatment of menopausal complaints: a non-interventional
      observational study over six cycles of 28 days.
AB  - BACKGROUND: Use of hormone therapy for menopausal complaints is a subject of
      controversy and increased uncertainty and concerns. This non-interventional study
      aimed to investigate a marketed oral formulation containing 1 mg estradiol and
      0.04 mg levonorgestrel for continuous treatment of menopausal symptoms for
      approximately 6 months in women visiting gynecological practices in Germany.
      METHODS: Changes in the menopause rating scale (MRS) total and sub-domain scores
      after three and six 28-d cycles served as primary endpoint. Skin- and hair
      related complaints, quality of sexual life and subjective satisfaction with the
      treatment were assessed. Adverse drug reactions (ADRs), adverse events (AEs) and
      vaginal bleeding were evaluated. RESULTS: MRS scores improved significantly above
      5 points of clinical relevance as compared to baseline (n = 736, p < 0.0001).
      Skin- and hair-related symptoms abated; quality of sexual life improved. AEs were
      registered in 9.9% of the participants. No unexpected ADRs were reported.
      Bleeding episodes consistently decreased; >75% of the subjects were amenorrheic
      throughout the study. Medication's effectiveness and tolerability was rated very
      good/good by >80% of the participants, who also continued treatment. CONCLUSION:
      This estradiol/low-dose levonorgestrel formulation safely alleviates menopausal
      symptoms in peri- and postmenopausal women with add-on benefits regarding
      dermatological and sexual life complaints.

PMID- 24905728
TI  - Resistance determinants and mobile genetic elements of an NDM-1-encoding
      Klebsiella pneumoniae strain.
AB  - Multidrug-resistant Enterobacteriaceae are emerging as a serious infectious
      disease challenge. These strains can accumulate many antibiotic resistance genes
      though horizontal transfer of genetic elements, those for beta-lactamases being
      of particular concern. Some beta-lactamases are active on a broad spectrum of
      beta-lactams including the last-resort carbapenems. The gene for the broad
      spectrum and carbapenem-active metallo-beta-lactamase NDM-1 is rapidly spreading.
      We present the complete genome of Klebsiella pneumoniae ATCC BAA-2146, the first
      U.S. isolate found to encode NDM-1, and describe its repertoire of antibiotic
      resistance genes and mutations, including genes for eight beta-lactamases and 15
      additional antibiotic-resistance enzymes. To elucidate the evolution of this rich
      repertoire, the mobile elements of the genome were characterized, including four
      plasmids with varying degrees of conservation and mosaicism and eleven
      chromosomal genomic islands. One island was identified by a novel phylogenomic
      approach, that further indicated the cps-lps polysaccharide synthesis locus,
      where operon translocation and fusion was noted. Unique plasmid segments and
      mosaic junctions were identified. Plasmid-borne blaCTX-M-15 was transposed
      recently to the chromosome by ISEcp1. None of the eleven full copies of IS26, the
      most frequent IS element in the genome, had the expected 8-bp direct repeat of
      the integration target sequence, suggesting that each copy underwent homologous
      recombination subsequent to its last transposition event. Comparative analysis
      likewise indicates IS26 as a frequent recombinational junction between plasmid
      ancestors, and also indicates a resolvase site. In one novel use of high
      throughput sequencing, homologously recombinant subpopulations of the bacterial
      culture were detected. In a second novel use, circular transposition
      intermediates were detected for the novel insertion sequence ISKpn21 of the ISNCY
      family, suggesting that it uses the two-step transposition mechanism of IS3.
      Robust genome-based phylogeny showed that a unified Klebsiella cluster contains
      Enterobacter aerogenes and Raoultella, suggesting the latter genus should be
      abandoned. 

PMID- 24905729
TI  - Characterization and treatment of persistent hepatocellular secretory failure.
AB  - BACKGROUND & AIMS: Hepatocellular secretory failure induced by drugs, toxins or
      transient biliary obstruction may sometimes persist for months after removal of
      the initiating factor and may then be fatal without liver transplantation. We
      characterized patients with severe persistent hepatocellular secretory failure
      (PHSF) and treated them with the pregnane X receptor (PXR) agonist, rifampicin.
      We also studied the effect of rifampicin on PXR-dependent expression of genes
      involved in biotransformation and secretion in vitro. METHODS: Thirteen patients
      (age 18-81 years, 6 male) with hepatocellular secretory failure that persisted
      after removal of the inducing factor (drugs/toxin: 9) or biliary obstruction (4)
      were identified over 6 years. Six of these patients were screened for ATP8B1 or
      ABCB11 mutations. All were treated with rifampicin (300 mg daily) for 1-10 weeks.
      Expression of genes involved in biotransformation and secretion was determined by
      rtPCR in human hepatocytes and intestinal cells incubated with rifampicin (10
      MUmol/L). RESULTS: Serum bilirubin of patients with PHSF ranged from 264 to 755
      MUmol/L. Normal gammaGT was found in 10/13 patients of whom 3/6 tested positive
      for ATP8B1/ABCB11 mutations. Serum bilirubin declined to <33 MUmol/L after 1-10
      weeks of rifampicin treatment. In vitro, rifampicin PXR-dependently upregulated
      biotransformation phase 1 (CYP3A4), phase 2 (UGT1A1) and phase 3 (MRP2)
      enzymes/carriers as well as the basolateral bile salt exporter OSTbeta.
      CONCLUSION: Persistent hepatocellular secretory failure may develop in carriers
      of transporter gene mutations. In severe cases, rifampicin may represent an
      effective therapeutic option of PHSF. PXR-dependent induction of CYP3A4, UGT1A1,
      MRP2 and OSTbeta could contribute to the anticholestatic effect of rifampicin in
      PHSF.

PMID- 24905731
TI  - Associations of all-cause mortality with census-based neighbourhood deprivation
      and population density in Japan: a multilevel survival analysis.
AB  - BACKGROUND: Despite evidence that neighbourhood conditions affect residents'
      health, no prospective studies of the association between neighbourhood socio
      demographic factors and all-cause mortality have been conducted in non-Western
      societies. Thus, we examined the effects of areal deprivation and population
      density on all-cause mortality in Japan. METHODS: We employed census and survival
      data from the Japan Public Health Center-based Prospective Study, Cohort I (n =
      37,455), consisting of middle-aged residents (40 to 59 years at the baseline in
      1990) living in four public health centre districts. Data spanned between 1990
      and 2010. A multilevel parametric proportional-hazard regression model was
      applied to estimate the hazard ratios (HRs) of all-cause mortality by two census
      based areal variables--areal deprivation index and population density--as well as
      individualistic variables such as socioeconomic status and various risk factors.
      RESULTS: We found that areal deprivation and population density had moderate
      associations with all-cause mortality at the neighbourhood level based on the
      survival data with 21 years of follow-ups. Even when controlling for
      individualistic socio-economic status and behavioural factors, the HRs of the two
      areal factors (using quartile categorical variables) significantly predicted
      mortality. Further, this analysis indicated an interaction effect of the two
      factors: areal deprivation prominently affects the health of residents in
      neighbourhoods with high population density. CONCLUSIONS: We confirmed that
      neighbourhood socio-demographic factors are significant predictors of all-cause
      death in Japanese non-metropolitan settings. Although further study is needed to
      clarify the cause-effect relationship of this association, the present findings
      suggest that health promotion policies should consider health disparities between
      neighbourhoods and possibly direct interventions towards reducing mortality in
      densely populated and highly deprived neighbourhoods.

PMID- 24905732
TI  - Genetics of the human metabolome, what is next?
AB  - Increases in throughput and decreases in costs have facilitated large scale
      metabolomics studies, the simultaneous measurement of large numbers of
      biochemical components in biological samples. Initial large scale studies focused
      on biomarker discovery for disease or disease progression and helped to
      understand biochemical pathways underlying disease. The first population-based
      studies that combined metabolomics and genome wide association studies (mGWAS)
      have increased our understanding of the (genetic) regulation of biochemical
      conversions. Measurements of metabolites as intermediate phenotypes are a
      potentially very powerful approach to uncover how genetic variation affects
      disease susceptibility and progression. However, we still face many hurdles in
      the interpretation of mGWAS data. Due to the composite nature of many
      metabolites, single enzymes may affect the levels of multiple metabolites and,
      conversely, levels of single metabolites may be affected by multiple enzymes.
      Here, we will provide a global review of the current status of mGWAS. We will
      specifically discuss the application of prior biological knowledge present in
      databases to the interpretation of mGWAS results and discuss the potential of
      mathematical models. As the technology continuously improves to detect
      metabolites and to measure genetic variation, it is clear that comprehensive
      systems biology based approaches are required to further our insight in the
      association between genes, metabolites and disease. This article is part of a
      Special Issue entitled: From Genome to Function.

PMID- 24905733
TI  - Axotrophin/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in
      vitro impairing microtubule binding.
AB  - Tau is the major microtubule-associated protein in neurons involved in
      microtubule stabilization in the axonal compartment. Changes in tau gene
      expression, alternative splicing and posttranslational modification regulate tau
      function and in tauopathies can result in tau mislocalization and dysfunction,
      causing tau aggregation and cell death. To uncover proteins involved in the
      development of tauopathies, a yeast two-hybrid system was used to screen for tau
      interacting proteins. We show that axotrophin/MARCH7, a RING-variant domain
      containing protein with similarity to E3 ubiquitin ligases interacts with tau. We
      defined the tau binding domain to amino acids 552-682 of axotrophin comprising
      the RING-variant domain. Co-immunoprecipitation and co-localization confirmed the
      specificity of the interaction. Intracellular localization of axotrophin is
      determined by an N-terminal nuclear targeting signal and a C-terminal nuclear
      export signal. In AD brain nuclear localization is lost and axotrophin is rather
      associated with neurofibrillary tangles. We find here that tau becomes mono
      ubiquitinated by recombinant tau-interacting RING-variant domain, which
      diminishes its microtubule-binding. In vitro ubiquitination of four-repeat tau
      results in incorporation of up to four ubiquitin molecules compared to two
      molecules in three-repeat tau. In summary, we present a novel tau modification
      occurring preferentially on 4-repeat tau protein which modifies microtubule
      binding and may impact on the pathogenesis of tauopathies. 

PMID- 24905735
TI  - From genome to phenome-Simple inborn errors of metabolism as complex traits.
AB  - Sporadically, patients with a proven defect in either mFAO or OXPHOS are
      described presenting with a metabolic profile and clinical phenotype expressing
      concurrent defects in both pathways. Biochemical linkages between both processes
      are tight. Therefore, it is striking that concurrent dysfunction of both systems
      occurs so infrequent. In this review, the linkages between OXPHOS and mFAO and
      the hypothesized processes responsible for concurrent problems in both systems
      are reviewed, both from the point of view of primary biochemical connections and
      secondary cellular responses, i.e. signaling pathways constituting nutrient
      sensing networks. We propose that affected signaling pathways may play an
      important role in the phenomenon of concurrent defects. Recent data indicate that
      interference in the affected signaling pathways may resolve the pathological
      phenotype even though the primary enzyme deficiency persists. This offers new
      (unexpected) prospects for treatment of these inborn errors of metabolism. This
      article is part of a Special Issue entitled: From Genome to Function.

PMID- 24905734
TI  - Energy crisis: the role of oxidative phosphorylation in acute inflammation and
      sepsis.
AB  - Mitochondrial dysfunction is increasingly recognized as an accomplice in most of
      the common human diseases including cancer, neurodegeneration, diabetes,
      ischemia/reperfusion injury as seen in myocardial infarction and stroke, and
      sepsis. Inflammatory conditions, both acute and chronic, have recently been shown
      to affect mitochondrial function. We here discuss the role of oxidative
      phosphorylation (OxPhos), focusing on acute inflammatory conditions, in
      particular sepsis and experimental sepsis models. We discuss mitochondrial
      alterations, specifically the suppression of oxidative metabolism and the role of
      mitochondrial reactive oxygen species in disease pathology. Several signaling
      pathways including metabolic, proliferative, and cytokine signaling affect
      mitochondrial function and appear to be important in inflammatory disease
      conditions. Cytochrome c oxidase (COX) and cytochrome c, the latter of which
      plays a central role in apoptosis in addition to mitochondrial respiration, serve
      as examples for the entire OxPhos system since they have been studied in more
      detail with respect to cell signaling. We propose a model in which inflammatory
      signaling leads to changes in the phosphorylation state of mitochondrial
      proteins, including Tyr304 phosphorylation of COX catalytic subunit I. This
      results in an inhibition of OxPhos, a reduction of the mitochondrial membrane
      potential, and consequently a lack of energy, which can cause organ failure and
      death as seen in septic patients. 

PMID- 24905736
TI  - A phylogeographic survey of the pygmy mouse Mus minutoides in South Africa:
      taxonomic and karyotypic inference from cytochrome b sequences of museum
      specimens.
AB  - The African pygmy mice (Mus, subgenus Nannomys) are a group of small-sized
      rodents that occur widely throughout sub-Saharan Africa. Chromosomal diversity
      within this group is extensive and numerous studies have shown the karyotype to
      be a useful taxonomic marker. This is pertinent to Mus minutoides populations in
      South Africa where two different cytotypes (2n = 34, 2n = 18) and a modification
      of the sex determination system (due to the presence of a Y chromosome in some
      females) have been recorded. This chromosomal diversity is mirrored by
      mitochondrial DNA sequences that unambiguously discriminate among the various
      pygmy mouse species and, importantly, the different M. minutoides cytotypes.
      However, the geographic delimitation and taxonomy of pygmy mice populations in
      South Africa is poorly understood. To address this, tissue samples of M.
      minutoides were taken and analysed from specimens housed in six South African
      museum collections. Partial cytochrome b sequences (400 pb) were successfully
      amplified from 44% of the 154 samples processed. Two species were identified: M.
      indutus and M. minutoides. The sequences of the M. indutus samples provided two
      unexpected features: i) nuclear copies of the cytochrome b gene were detected in
      many specimens, and ii) the range of this species was found to extend
      considerably further south than is presently understood. The phylogenetic
      analysis of the M. minutoides samples revealed two well-supported clades: a
      Southern clade which included the two chromosomal groups previously identified in
      South Africa, and an Eastern clade that extended from Eastern Africa into South
      Africa. Congruent molecular phylogenetic and chromosomal datasets permitted the
      tentative chromosomal assignments of museum specimens within the different clades
      as well as the correction of misidentified museum specimens. 

PMID- 24905737
TI  - Diagnostic performance of the PTSD checklist and the Vietnam Era Twin Registry
      PTSD scale.
AB  - AIMS: Self-report questionnaires are frequently used in clinical and
      epidemiologic studies to assess post-traumatic stress disorder (PTSD). A number
      of studies have evaluated these scales relative to clinician administered
      structured interviews; however, there has been no formal evaluation of their
      performance relative to non-clinician administered epidemiologic assessments such
      as the Composite International Diagnostic Interview (CIDI). We examined the
      diagnostic performance of two self-report PTSD scales, the PTSD checklist (PCL)
      and the Vietnam Era Twin Registry (VET-R) PTSD scale, compared to the CIDI.
      METHODS: Data were derived from a large epidemiologic follow-up study of PTSD in
      5141 Vietnam Era Veterans. Measures included the PCL, VET-R PTSD scale and CIDI.
      For both the PCL and VET-R PTSD scale, ROC curves, areas under the curve (AUC),
      sensitivity, specificity, % correctly classified, likelihood ratios, predictive
      values and quality estimates were generated based on the CIDI PTSD diagnosis.
      RESULTS: For the PCL and VET-R PTSD scale the AUCs were 89.0 and 87.7%,
      respectively. Optimal PCL cutpoints varied from the 31-33 range (when considering
      sensitivity and specificity) to the 36-56 range (when considering quality
      estimates). Similar variations were found for the VET-R PTSD, ranging from 31
      (when considering sensitivity and specificity) to the 37-42 range (when
      considering quality estimates). CONCLUSIONS: The PCL and VET-R PTSD scale
      performed similarly using a CIDI PTSD diagnosis as the criterion. There was a
      range of acceptable cutpoints, depending on the metric used, but most metrics
      suggested a lower PCL cutpoint than in previous studies in Veteran populations.

PMID- 24905739
TI  - Designing Issues in Confirmatory Adaptive Population Enrichment Trials.
AB  - Adaptive population enrichment designs enable the data-driven selection of one or
      more pre-specified subpopulations in an interim analysis, and the confirmatory
      proof of efficacy in the selected subset at the end of the trial. Sample size
      reassessment and other adaptive design changes can be performed as well. Strong
      control of the experimentwise Type I error rate is guaranteed by use of the
      combination testing principle together with the closed testing argument. In this
      paper the general methodology and designing issues when planning such a design
      are reviewed. It is shown how to derive overall confidence intervals and p
      values. Criteria for assessing the operating characteristics of these designs are
      given, and the application is illustrated by examples. 

PMID- 24905738
TI  - Perturbing the cellular levels of steroid receptor coactivator-2 impairs murine
      endometrial function.
AB  - As pleiotropic coregulators, members of the p160/steroid receptor coactivator
      (SRC) family control a broad spectrum of transcriptional responses that underpin
      a diverse array of physiological and pathophysiological processes. Because of
      their potent coregulator properties, strict controls on SRC expression levels are
      required to maintain normal tissue functionality. Accordingly, an unwarranted
      increase in the cellular levels of SRC members has been causally linked to the
      initiation and/or progression of a number of clinical disorders. Although
      knockout mouse models have underscored the critical non-redundant roles for each
      SRC member in vivo, there are surprisingly few mouse models that have been
      engineered to overexpress SRCs. This deficiency is significant since SRC
      involvement in many of these disorders is based on unscheduled increases in the
      levels (rather than the absence) of SRC expression. To address this deficiency,
      we used recent mouse technology that allows for the targeted expression of human
      SRC-2 in cells which express the progesterone receptor. Through cre-loxP
      recombination driven by the endogenous progesterone receptor promoter, a marked
      elevation in expression levels of human SRC-2 was achieved in endometrial cells
      that are positive for the progesterone receptor. As a result of this increase in
      coregulator expression, female mice are severely subfertile due to a
      dysfunctional uterus, which exhibits a hypersensitivity to estrogen exposure. Our
      findings strongly support the proposal from clinical observations that increased
      levels of SRC-2 are causal for a number of endometrial disorders which compromise
      fertility. Future studies will use this mouse model to decipher the molecular
      mechanisms that underpin the endometrial defect. We believe such mechanistic
      insight may provide new molecular descriptors for diagnosis, prognosis, and/or
      therapy in the clinical management of female infertility. 

PMID- 24905741
TI  - Lipidomics for clinical diagnosis: Dye-Assisted Laser Desorption/Ionization
      (DALDI) method for lipids detection in MALDI mass spectrometry imaging.
AB  - Lipid-based biomarkers for research and diagnosis are rapidly emerging to unpack
      the basis of person-to-person and population variations in disease
      susceptibility, drug and nutritional responses, to name but a few. Hence, with
      the advent of MALDI Mass Spectrometry Imaging, lipids have begun to be
      investigated intensively. However, lipids are highly mobile during tissue
      preparation, and are soluble in the solvent used for matrix preparation or in the
      fixing fluid such as formalin, resulting in substantial delocalization. In the
      present article, we investigated as another alternative, the possibility of using
      specific dyes that can absorb UV wavelengths, in order to desorb the lipids
      specifically from tissue sections, and are known to immobilize them in tissues.
      Indeed, after lipid insolubilization with chromate solution or chemical fixation
      with osmium tetroxide, heterocyclic-based dyes can be directly used without
      matrix. Taking into account the fact that some dyes have this matrix-free
      capability, we identified particular dyes dedicated to histological staining of
      lipids that could be used with MALDI mass spectrometry imaging. We stained tissue
      sections with either Sudan Black B, Nile Blue A, or Oil Red O. An important
      advantage of this assay relies on its compatibility with usual practices of
      histopathological investigation of lipids. As a new method, DALDI stands for Dye
      Assisted Laser Desorption Ionization and allows for future clinical and
      histopathological applications using routine histological protocols.
      Additionally, this novel methodology was validated in human ovarian cancer
      biopsies to demonstrate its use as a suitable procedure, for histological
      diagnosis in lipidomics field.

PMID- 24905743
TI  - Morphological analysis of the pancreas and liver in diabetic KK-A(y) mice treated
      with zinc and oxovanadium complexes.
AB  - The relationship between biometals, such as zinc (Zn(2+)), vanadium, copper,
      cobalt, and magnesium ions, and diabetes therapy has been recognized for several
      years. In particular, the antidiabetic activities of Zn(2+) and oxovanadium
      (VO(2+)) complexes have been measured using biochemical approaches. In the
      present study, diabetic KK-A(y) mice were treated with bis(1-oxy-2-pyridine
      thiolato)Zn(2+) (Zn(opt)2) and bis(1-oxy-2-pyridine-thiolato)VO(2+) (VO(opt)2)
      for 4 weeks, and the antidiabetic activities of these metal complexes were
      evaluated using biochemical and morphological methods. Additionally, zinc
      gluconate (Zn(glc)2) and bis(ethylmaltolato)VO(2+) (VO(emal)2) were used as
      reference compounds. Pancreatic islet cells were smaller, and there was a
      tendency towards a lower islet cell area ratio in Zn(opt)2-treated mice compared
      with nontreated KK-A(y) mice. Furthermore, plasma insulin concentrations were
      significantly reduced to 27.2% of insulin concentrations in nontreated KK-A(y)
      mice. These results suggest that Zn(opt)2 administration provides morphological
      and biochemical improvements in hyperinsulinaemia. In contrast, in mice that
      received Zn(glc)2 and VO(2+) complexes, the islet cell size and islet cell area
      ratio did not differ from those in nontreated controls. Zn(opt)2- and VO(opt)2
      treated mice exhibited significantly lower fat deposition and fat deposition area
      ratio in the liver (63.6% and 65.8% of nontreated KK-A(y) mice, respectively)
      compared to those observed in nontreated KK-A(y) mice. The differences in
      morphological improvements of the pancreas and liver owing to Zn(opt)2 or
      VO(opt)2 treatment may be explained by differences in the sites of actions of
      Zn(2+) and VO(2+) complexes in different organs in KK-A(y) mice. In conclusion,
      Zn(opt)2 exhibited superior antidiabetic effects over those of VO(opt)2, and this
      was owing to greater amelioration of the morphological parameters of the liver
      and pancreas. 

PMID- 24905740
TI  - Associations of filaggrin gene loss-of-function variants and human papillomavirus
      related cancer and pre-cancer in Danish adults.
AB  - PURPOSE: Filaggrin proteins are expressed in the skin, oral cavity, oesophagus,
      and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG)
      reduce filaggrin expression and cause an impaired skin barrier function. We
      hypothesized that FLG mutation carriers would be more susceptible to human
      papillomavirus (HPV) infection and thus a higher risk of HPV-related cancer and
      pre-cancer. We investigated the association of the FLG genotype with incidence of
      HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and
      pre-cancer of the cervix. METHODS: We included 13,376 persons from four
      population-based studies conducted in the same background population in
      Copenhagen, Denmark. Participants were genotyped for the most common FLG
      mutations in Europeans. Information on cancer was obtained from The Danish Cancer
      Registry until 11 July 2011. RESULTS: There were 489 cases of prevalent and 97
      cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5
      years). There was a statistically significant association between FLG genotype
      and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95%
      confidence intervals, CI: 1.2, 3.7) for FLG mutation carriers vs. wild types.
      CONCLUSIONS: FLG loss-of-function mutations were associated with higher incidence
      of HPV-related cancers and pre-cancers that are potentially screening and vaccine
      preventable.

PMID- 24905745
TI  - Sources of health information among rural women in Western Kentucky.
AB  - OBJECTIVE: To identify sources of general and mental health information for rural
      women to inform the development of public health nursing interventions that
      consider preferences for obtaining information. DESIGN AND SAMPLE: One thousand
      women (mean age = 57 years; 96.9% White) living in primarily nonmetropolitan
      areas of Western Kentucky participated via a random-digit-dial survey. MEASURES:
      Data were collected on demographics, sources of health information, depression,
      and stigma. RESULTS: Most participants preferred anonymous versus interpersonal
      sources for both general (68.1%) and mental health (69.4%) information. All
      participants reported at least one source of general health information, but
      20.8% indicated not seeking or not knowing where to seek mental health
      information. The Internet was the most preferred anonymous source. Few women
      cited health professionals as the primary information source for general (11.4%)
      or mental (9.9%) health. Public stigma was associated with preferring anonymous
      sources and not seeking information. CONCLUSIONS: Public health nurses should
      understand the high utilization of anonymous sources, particularly for mental
      health information, and focus efforts on helping individuals to navigate
      resources to ensure they obtain accurate information about symptoms, effective
      treatments, and obtaining care. Reducing stigma should remain a central focus of
      prevention and education in rural areas.

PMID- 24905744
TI  - Two domains of the smoothelin-like 1 protein bind apo- and calcium-calmodulin
      independently.
AB  - The smoothelin-like 1 protein (SMTNL1) is a modulator of smooth and skeletal
      muscle contractility and can bind to calmodulin and tropomyosin. Calmodulin is
      the major calcium sensor of eukaryotic cells and it can cycle between calcium
      free (apo-CaM) and calcium-bound (Ca-CaM) forms. Bioinformatic screening of the
      SMTNL1 sequence predicted a second CaM-binding region (CBD1) that is located N
      terminal to the previously defined apo-CaM-binding site (CBD2). Pull-down assays,
      surface plasmon resonance, isothermal calorimetry and NMR techniques were used to
      determine that CBD1 associated preferentially to Ca-CaM while CBD2 bound
      preferentially to apo-CaM. Mutation of hydrophobic residues abolished Ca-CaM
      binding to CBD1 while acidic residues in CBD2 were necessary for apo-CaM-binding
      to CBD2. The dissociation constant (Kd) for Ca-CaM-binding to a CBD1 peptide was
      26*10(-6)M while the value for binding to a longer protein construct was 0.5*10(
      6)M. The binding of SMTNL1 to both apo-CaM and Ca-CaM suggests that endogenous
      CaM is continuously associated with SMTNL1 to allow for quick response to changes
      in intracellular calcium levels. We also found that the intrinsically disordered
      N-terminus of SMTNL1 can reduce binding to apo-CaM and increase binding to Ca
      CaM. This finding suggests that an additional CaM-binding region may exist and/or
      that intramolecular interactions between the N-terminus and the folded C-terminus
      reduce apo-CaM-binding to CBD2. Intriguingly, CBD1 is located close to the SMTNL1
      phosphorylation site and tropomyosin-binding region. We discuss the possibility
      that all three signals are integrated at the region surrounding CBD1. 

PMID- 24905747
TI  - Chill out with rockcress: quantitative genetics of frost tolerance in the North
      American wild perennial Boechera stricta.

PMID- 24905746
TI  - Disruption of crosstalk between mesenchymal stromal and tumor cells in bone
      marrow as a therapeutic target to prevent metastatic bone disease.
AB  - Skeletal metastasis is a serious complication of many primary cancers. A common
      feature of tumor cells that metastasize to the bone marrow microenvironment is
      that they initiate a cascade of events, recruiting and presumably/potentially
      altering the phenotype of bone marrow mesenchymal stromal cells (MSC) to produce
      an environment that allows for tumor growth and in some cases, drug-resistant
      dormancy of latent cancer cells. Consequently the MSC population can contribute
      to metastatic disease through several distinct mechanisms by differentiating into
      cancer-associated fibroblasts (CAFs). Understanding the expression and epigenetic
      changes that occur as normal MSCs become associated with metastatic tumors would
      reveal possible therapeutic targets for treating skeletal metastasis.

PMID- 24905748
TI  - Sasa borealis stem extract attenuates hepatic steatosis in high-fat diet-induced
      obese rats.
AB  - The aim of the current study is to examine the improving effect of Sasa borealis
      stem (SBS) extract extracts on high-fat diet (HFD)-induced hepatic steatosis in
      rats. To determine the hepatoprotective effect of SBS, we fed rats a normal
      regular diet (ND), HFD, and HFD supplemented with 150 mg/kg body weight (BW) SBS
      extracts for five weeks. We found that the body weight and liver weight of rats
      in the HFD + SBS group were significantly lower than those in the HFD group.
      Significantly lower serum total cholesterol (TC) and triglyceride (TG)
      concentrations were observed in the SBS-supplemented group compared with the HFD
      group. We also found that the HFD supplemented with SBS group showed dramatically
      reduced hepatic lipid accumulation compared to the HFD alone group, and
      administration of SBS resulted in dramatic suppression of TG, TC in the HFD
      induced fatty liver. In liver gene expression within the SBS treated group,
      PPARalpha was significantly increased and SREBP-1c was significantly suppressed.
      SBS induced a significant decrease in the hepatic mRNA levels of PPARgamma, FAS,
      ACC1, and DGAT2. In conclusion, SBS improved cholesterol metabolism, decreased
      lipogenesis, and increased lipid oxidation in HFD-induced hepatic steatosis in
      rats, implying a potential application in treatment of non-alcoholic fatty liver
      disease. 

PMID- 24905749
TI  - Emerging roles of microRNAs in chronic pain.
AB  - Chronic pain is a debilitating syndrome caused by a variety of disorders, and
      represents a major clinical problem because of the lack of adequate medication.
      In chronic pain, massive changes in gene expression are observed in a variety of
      cells, including neurons and glia, in the overall somatosensory system from the
      sensory ganglia to the higher central nervous system. The protein expressions of
      hundreds of genes are thought to be post-transcriptionally regulated by a single
      type of microRNA in a sequence-specific manner. Recently, critical roles of
      microRNAs in the pathophysiology of chronic pain have been emerging. Genome-wide
      screenings of microRNA expression changes have been reported in a variety of
      painful conditions, including peripheral nerve injury, inflammatory diseases,
      cancer and spinal cord injury. The data obtained suggest that a wide range of
      microRNAs change their expressions in individual pain conditions, although the
      pathological significance of individual microRNAs as causal mediators in distinct
      pain conditions remains to be revealed for a limited number of microRNAs.
      Insights into the roles of microRNAs in chronic pain will enhance our
      understanding of the pathophysiology of chronic pain and allow prompt therapeutic
      application of microRNA-related drugs against intractable persistent pain. 

PMID- 24905751
TI  - Maintaining a strong yeast research community.

PMID- 24905752
TI  - Emotional working memory during sustained wakefulness.
AB  - In the present study we investigated whether one night of sleep deprivation can
      affect working memory (WM) performance with emotional stimuli. Twenty-five
      subjects were tested after one night of sleep deprivation and after one night of
      undisturbed sleep at home. As a second aim of the study, to evaluate the
      cumulative effects of sleep loss and of time-of-day changes on emotional WM
      ability, the subjects were tested every 4 h, from 22:00 to 10:00 hours, in four
      testing sessions during the sleep deprivation period (deprivation sessions: D1,
      D2, D3 and D4). Subjects performed the following test battery: Psychomotor
      Vigilance Task, 0-back task, 2-back task and an 'emotional 2-back task' with
      neutral, positive and negative emotional pictures selected from the International
      Affective Picture System. Results showed lower accuracy in the emotional WM task
      when the participants were sleep-deprived relative to when they had slept,
      suggesting the crucial role of sleep for preserving WM ability. In addition, the
      accuracy for the negative pictures remains stable during the sessions performed
      from 22:00 to 06:00 hours (D1, D2 and D3), while it drops at the D4 session, when
      the participants had accumulated the longest sleep debt. It is suggested that,
      during sleep loss, attentional and WM mechanisms may be sustained by the higher
      arousing characteristics of the emotional (negative) stimuli. 

PMID- 24905750
TI  - B cells and ectopic follicular structures: novel players in anti-tumor
      programming with prognostic power for patients with metastatic colorectal cancer.
AB  - Remarkably limited information is available about biological mechanisms that
      determine the disease entity of metastatic colorectal cancer in the liver (CRCLM)
      with no good clinical parameters to estimate prognosis. For the last few years,
      understanding the relationship between tumor characteristics and local immune
      response has gained increasing attention. Given the multifaceted roles of B-cell
      driven responses, we aimed to elucidate the immunological imprint of B
      lymphocytes at the metastatic site, the interrelation with macrophages, and their
      prognostic relevance. Here we present novel algorithm allowing to assess a link
      between the local patient-specific immunological capacity and clinical outcome.
      The microscopy-based imaging platform was used for automated scanning of large
      scale tissue sections and subsequent qualitative and quantitative analyses of
      immune cell subtypes using lineage markers and single-cell recognition strategy.
      Results indicate massive infiltration of CD45-positive leukocytes confined to the
      metastatic border. We report for the first time the accumulation of CD20-positive
      B lymphocytes at the tumor-liver interface comprising the major population within
      the large CD45-positive aggregates. Strikingly, functionally active, activation
      induced cytidine deaminase (AID)-positive ectopic lymphoid structures were found
      to be assembled within the metastatic margin. Furthermore, the CD20-based data
      set revealed a strong prognostic power: patients with high CD20 content and/or
      ectopic follicles had significantly lower risk for disease recurrence as revealed
      by univariate analysis (p<0.001 for both) and in models adjusted for
      clinicopathological variables (p<0.001 and p = 0.01, respectively), and showed
      prolonged overall survival. In contrast, CD68 staining-derived data set did not
      show an association with clinical outcome. Taken together, we nominate the
      magnitude of B lymphocytes, including those organized in ectopic follicles, as
      novel prognostic marker which is superior to clinicopathological parameters.
      Findings emphasize anti-tumoral role of B cell-driven mechanism(s) and thus
      indicate a new way of thinking about potential treatment strategies for CRCLM
      patients.

PMID- 24905753
TI  - Hierarchicality of trade flow networks reveals complexity of products.
AB  - With globalization, countries are more connected than before by trading flows,
      which amounts to at least 36 trillion dollars today. Interestingly, around 30-60
      percents of exports consist of intermediate products in global. Therefore, the
      trade flow network of particular product with high added values can be regarded
      as value chains. The problem is weather we can discriminate between these
      products from their unique flow network structure? This paper applies the flow
      analysis method developed in ecology to 638 trading flow networks of different
      products. We claim that the allometric scaling exponent eta can be used to
      characterize the degree of hierarchicality of a flow network, i.e., whether the
      trading products flow on long hierarchical chains. Then, it is pointed out that
      the flow networks of products with higher added values and complexity like
      machinary, transport equipment etc. have larger exponents, meaning that their
      trade flow networks are more hierarchical. As a result, without the extra data
      like global input-output table, we can identify the product categories with
      higher complexity, and the relative importance of a country in the global value
      chain by the trading network solely.

PMID- 24905754
TI  - Prescription drugs or heroin: the overdoses continue.

PMID- 24905755
TI  - Protective factors against relapse for practicing nurse anesthetists in recovery
      from anesthetic opiate dependency.
AB  - This qualitative inquiry explored factors that protect recovering anesthetic
      opioid-dependent nurse anesthetists from relapse after their return to anesthesia
      practice. Practicing nurse anesthetists in recovery from potent opioids were
      recruited through online advertising and individually interviewed over the
      telephone. The interview consisted of open-ended questions that aided description
      of personal experience of individual factors. Content analysis of the interviews
      revealed an overarching theme of a commitment to the recovery process, which
      provided the foundational protective element against relapse. Within this
      context, two major thematic factors emerged: personal factors and external
      factors. Personal factors came from within the individual and included such
      features as removing the obsession to use, self-realization, inner strength, and
      seeing the future. External factors were external to the individual and described
      as time away from practice, state regulatory agency involvement, and talking with
      significant others. Although the Twelve-Step process was not a factor per se, it
      was credited by all participants as the structure on which their recovery was
      built. This process provided mechanisms for developing the motivation and
      learning the tools necessary to maintain their sobriety. 

PMID- 24905756
TI  - Measuring chronic pain intensity among veterans in a residential rehabilitation
      treatment program.
AB  - The purpose of this study was to identify whether veterans with chronic pain,
      substance abuse, and posttraumatic stress disorder (PTSD) diagnoses residing in a
      Residential Rehabilitation Treatment Program (RRTP) perceived a higher level of
      pain than those veterans who had chronic pain but did not have active substance
      abuse issues or PTSD. A sample of veterans (n = 200) with chronic pain undergoing
      treatment for either chemical dependency and/or PTSD in an RRTP and a Surgical
      Specialty Care outpatient clinic at a Department of Veterans Affairs medical
      center took part in the study. Multiple analysis of variance and further
      univariate statistics were examined to determine the association between groups
      on the different scales. There was a considerable difference in terms of which
      group of veterans perceived a higher rate of pain even with the use of the same
      four pain assessment scales (i.e., Numeric Rating, Visual Analog, Faces, and
      Mankoski). Scores were significantly higher for the RRTP group than the Surgical
      Specialty Care group on all screening measures (p < .001). Veterans with chronic
      pain, substance abuse, and/or PTSD diagnoses residing in an RRTP tended to have a
      higher perception of chronic pain compared to those without substance abuse or
      PTSD diagnoses. 

PMID- 24905757
TI  - Assessing the extent to which healthcare workers advised and assisted smokers to
      quit based on patient motivation levels.
AB  - Smoking remains the leading cause of preventable death in the United States.
      Although healthcare workers play a key role in helping patients quit smoking, the
      degree to which they provide help varies. This study assesses the extent to which
      smokers report that their healthcare worker advised and assisted them with
      quitting based on their level of readiness to make a change. The 2006 Hawaii
      Adult Tobacco Survey asked questions regarding smoking status and if advice and
      assistance with quitting was given from a healthcare worker. Percentages for
      reporting healthcare worker's advice and assistance were compared among the three
      levels of motivational readiness using the chi-square test of association for 331
      current, everyday smokers (56% women; 38% in the age group of 45-54 years). Most
      smokers are given advice to quit smoking. However, only about half of those
      motivated to quit are given assistance to do so. Most smokers across all
      motivation levels received advice to quit smoking with no significant difference
      between levels of readiness to quit. Less than half of smokers received any type
      of assistance with quitting smoking, with higher motivated smokers significantly
      receiving more assistance with cessation medication or nicotine replacement
      therapy and setting a quit date. This is a call to action for healthcare workers
      to address smoking with every patient. Adjustments to protocols for addressing
      smoking cessation and readiness to quit may be warranted. 

PMID- 24905759
TI  - Differences in risk perception and quit rates among hospitalized veteran pipe
      smokers, cigarette smokers, and dual users.
AB  - OBJECTIVE: This study examined differences in perception of risk, hospitalization
      quit rates, and 6-month quit rates between pipe smokers, cigarettes smokers, and
      those who smoke both in the Department of Veterans Affairs. METHODS: Before
      implementing the Tobacco Tactics intervention (among 811 smokers), smoking quit
      rates were determined (among N = 465 patients with 6-month follow-up data
      available) in three Midwestern hospitals during 2006-2010. RESULTS: Pipe smokers
      were less likely to believe that they needed to quit tobacco, that quitting would
      be difficult, and that quitting tobacco was important to their health. Eighty
      five percent of pipe smokers remained tobacco free throughout their hospital stay
      compared with 59% of dual smokers and 60% of cigarette smokers (p < .10). Twenty
      three percent of pipe smokers remained tobacco free at 6 months compared with 19%
      of dual users and 7% of cigarette smokers (p < .10). CONCLUSION: Although pipe
      smokers had higher spontaneous quit rates than dual smokers and cigarette
      smokers, the perception of the risk of smoking was less among pipe smokers
      suggesting a need to expel the myths surrounding pipe smoking and increase
      cessation efforts.

PMID- 24905760
TI  - Determination of smoking and drinking and preventive measures in adolescents.
AB  - Smoking and alcohol drinking in adolescents cause significant problems in most
      countries. The aim of this cross-sectional descriptive study was to determine the
      prevalence, causes, risk factors, and preventive factors for cigarette and
      alcohol use in adolescents. The sample included 1,133 students enrolled in grades
      9-12. Data were collected using a descriptive data form, the Psychological
      Resilience and Adolescent Development Scale, and the Family Environment Scale.
      Most adolescents stated that stress and psychological problems were the causes of
      smoking and alcohol use. Preventive factors were indicated as developing skills
      for saying "no," good coping skills, and peer groups not using cigarettes. The
      Psychological Resilience and Adolescent Development Scale mean score for
      cigarette and alcohol use was significantly higher than for nonuse. The Family
      Environment Scale mean score for cigarette and alcohol use was significantly
      lower than for nonuse. 

PMID- 24905761
TI  - Pharmacology corner. Buprenorphine.

PMID- 24905762
TI  - Educating individuals and communities about drugs and addiction.

PMID- 24905763
TI  - An interview with Laurence Tisserand, RN: an innovative care model in France.

PMID- 24905764
TI  - Mapping of amino acid substitutions conferring herbicide resistance in wheat
      glutathione transferase.
AB  - We have used design of experiments (DOE) and systematic variance to efficiently
      explore glutathione transferase substrate specificities caused by amino acid
      substitutions. Amino acid substitutions selected using phylogenetic analysis were
      synthetically combined using a DOE design to create an information-rich set of
      gene variants, termed infologs. We used machine learning to identify and quantify
      protein sequence-function relationships against 14 different substrates. The
      resulting models were quantitative and predictive, serving as a guide for
      engineering of glutathione transferase activity toward a diverse set of
      herbicides. Predictive quantitative models like those presented here have broad
      applicability for bioengineering. 

PMID- 24905765
TI  - Exciton kinetics, quantum efficiency, and efficiency droop of monolayer MoS2
      light-emitting devices.
AB  - We have investigated the quantum efficiency of monolayer MoS2 light-emitting
      devices through detailed temperature and power-dependent photoluminescence
      studies and rate equation analysis. The internal quantum efficiency can reach 45
      and 8.3% at 83 and 300 K, respectively. However, efficiency droop is clearly
      measured with increasing carrier injection due to the unusually large Auger
      recombination coefficient, which is found to be ~10(-24) cm(6)/s at room
      temperature, nearly 6 orders of magnitude higher than that of conventional bulk
      semiconductors. The significantly elevated Auger recombination in the emerging
      two-dimensional (2D) semiconductors is primarily an indirect process and is
      attributed to the abrupt bounding surfaces and the enhanced correlation, mediated
      by magnified Coulomb interactions, between electrons and holes confined in a 2D
      structure.

PMID- 24905766
TI  - Peptidophospholipids: synthesis, phospholipase A2 catalyzed hydrolysis, and
      application to development of phospholipid prodrugs.
AB  - New phospholipid analogues incorporating sn-2-peptide substituents have been
      prepared to probe the fundamental structural requirements for phospholipase A2
      catalyzed hydrolysis of PLA2-directed synthetic substrates. Two structurally
      different antiviral oligopeptides with C-terminal glycine were introduced
      separately at the sn-2-carboxylic ester position of phospholipids to assess the
      role of the alpha-methylene group adjacent to the ester carbonyl in allowing
      hydrolytic cleavage by the enzyme. The oligopeptide-carrying phospholipid
      derivatives were readily incorporated into mixed micelles consisting of natural
      phospholipid (dipalmitoyl phosphatidylcholine, DPPC) and Triton X-100 as
      surfactant. Hydrolytic cleavage of the synthetic peptidophospholipids by the
      phospholipase A2 occurred slower, but within the same order of magnitude as the
      natural substrate alone. The results provide useful information toward better
      understanding the mechanism of action of the enzyme, and to improve the design
      and synthesis of phospholipid prodrugs targeted at secretory PLA2 enzymes. 

PMID- 24905767
TI  - Lower activity levels are related to higher plantar pressures in overweight
      children.
AB  - PURPOSE: This study aimed to establish whether the peak plantar pressures
      generated by overweight and obese school-age children during walking were
      associated with their objectively measured physical activity. METHODS: Physical
      activity levels of a subset of 73 overweight/obese children from a randomized
      controlled trial (mean +/- SD: age, 8.3 +/- 1.1 yr; 47 girls; body mass index z
      score, 2.7 +/- 0.7) were objectively measured using accelerometers. Plantar
      pressure distributions were also quantified as the participants walked over a
      pressure platform. Pearson product moment correlation coefficients were
      calculated to determine the strength of the relations between the peak plantar
      pressures generated during walking and the physical activity levels for
      overweight/obese children. RESULTS: Peak pressures generated beneath the forefoot
      during walking were inversely correlated with time spent in different intensity
      levels of physical activity. Moderate-intensity (r = -0.321, P = 0.007), vigorous
      intensity (r = -0.326, P = 0.006), and moderate- to vigorous-intensity (r = 
      0.342, P = 0.004) physical activity were significantly correlated with middle
      forefoot pressure and with lateral forefoot pressure (r = -0.248, P = 0.040; r = 
      0.264, P = 0.028; r = -0.267, P = 0.027, respectively). Lateral midfoot (r = 
      0.244, P = 0.044) and second toe (r = 0.227, P = 0.021) pressure were also
      significantly correlated with vigorous-intensity activity. CONCLUSIONS: Those
      children who generated higher pressures beneath their forefoot and midfoot during
      walking had lower levels of physical activity. Further research is required to
      determine the long-term effects of excessive body mass on participation in
      physical activity and whether the walking plantar pressure patterns associated
      with reduced physical activity are related to foot pain or discomfort.

PMID- 24905768
TI  - Mesenchymal stem cells augment the adaptive response to eccentric exercise.
AB  - PURPOSE: The alpha7beta1 integrin is a transmembrane protein expressed in the
      skeletal muscle that can link the actin cytoskeleton to the surrounding basal
      lamina. We have previously demonstrated that transgenic mice overexpressing the
      alpha7B integrin in the skeletal muscle (MCK:alpha7B; alpha7Tg) mount an enhanced
      satellite cell and growth response to single or multiple bouts of eccentric
      exercise. In addition, interstitial stem cells characterized as mesenchymal stem
      cells (MSCs) accumulate in alpha7Tg muscle (mMSCs) in the sedentary state and
      after exercise. The results from these studies prompted us to determine the
      extent to which mMSC underlie the beneficial adaptive responses observed in
      alpha7Tg skeletal muscle after exercise. METHODS: mMSCs (Sca-1CD45) were isolated
      from alpha7Tg mice, dye-labeled, and intramuscularly injected into adult wild
      type recipient mice. After injection of mMSCs or saline, mice remained sedentary
      (SED) or were subjected to eccentric exercise training (TR) (downhill running) on
      a treadmill (three times per week) for 2 or 4 wk. Gastrocnemius-soleus complexes
      were collected 24 h after the last bout of exercise. RESULTS: mMSCs did not
      directly fuse with existing fibers; however, mMSCs injection enhanced Pax7
      satellite cell number and myonuclear content compared with all other groups at 2
      wk after exercise. Mean CSA, percentage of larger caliber fibers (>3000 MUm), and
      grip strength were increased in mMSCs/TR compared with saline/SED and mMSCs/SED
      at 4 wk. mMSC transplantation did not enhance repair or growth in the absence of
      exercise. CONCLUSIONS: The results from this study demonstrate that mMSCs
      contribute to beneficial changes in satellite cell expansion and growth in
      alpha7Tg muscle after eccentric exercise. Thus, MSCs that naturally accumulate in
      the muscle after eccentric contractions may enhance the adaptive response to
      exercise.

PMID- 24905769
TI  - The first case of bacteraemia due to non-O1/non-O139 Vibrio cholerae in a type 2
      diabetes mellitus patient in mainland China.
AB  - Bacteraemia due to non-O1/non-O139 Vibrio cholerae is rarely documented in
      mainland China. We report such a case in a 70-year-old male with type 2 diabetes
      mellitus. The clinical features, phenotypic analyses, and presence of a panel of
      known virulence genes in the isolated strain are described. To the best of our
      knowledge, this is the first reported case of bacteraemia due to this strain in a
      T2DM patient without other coexisting underlying diseases in mainland China. 

PMID- 24905770
TI  - Choosing the right rituximab dose for the right patient: comment on the article
      by Bredemeier et al.

PMID- 24905771
TI  - The study of severe cutaneous drug hypersensitivity reactions from a systems
      biology perspective.
AB  - PURPOSE OF REVIEW: Stevens-Johnson syndrome and toxic epidermal necrolysis are
      severe hypersensitivity reactions, the majority of which are drug induced. The
      underlying mechanisms are not fully understood. Here, we review recent findings
      concerning both mechanistic and genetic factors related to these diseases and
      propose future approaches to unravel their complexity. RECENT FINDINGS: Genome
      wide association study studies have identified several variants in the human
      leukocyte antigen region associated with these reactions. These are highly
      dependent on the population studied and the triggering drug. The T-cell receptor
      repertoire of the patient is also key. Fas-Fas ligand interactions, perforin and
      granulysin have also been identified as important players. Furthermore, a high
      throughput gene expression study has identified a number of genes that increase
      in expression in patients during the acute phase of these reactions. SUMMARY: We
      review recent high-throughput studies on these diseases and suggest ways in which
      the data can be combined and reanalyzed using integrative systems biology
      techniques. We also suggest future lines of research using recent technology that
      could shed further light on their underlying mechanisms.

PMID- 24905773
TI  - Endometrial cancer: a review and current management strategies: part I.
AB  - Endometrial carcinoma is the most common gynecologic malignancy. A thorough
      understanding of the epidemiology, pathophysiology, and management strategies for
      this cancer allows the obstetrician-gynecologist to identify women at increased
      risk, contribute toward risk reduction, and facilitate early diagnosis. The
      Society of Gynecologic Oncology's Clinical Practice Committee has reviewed the
      literature and created evidence-based practice recommendations for diagnosis and
      treatment. This article examines: * Risk factors, including genetic
      predisposition * Diagnostic and metastatic evaluation * Surgical management of
      early and advanced cancer, including lymphadenectomy in early cancer.

PMID- 24905772
TI  - Accuracy of dry vaginal self-sampling for detecting high-risk human
      papillomavirus infection in cervical cancer screening: a cross-sectional study.
AB  - OBJECTIVE: Cervical cancer screening coverage remains insufficient in most
      countries. Testing self-collected samples for high-risk human papillomavirus (HR
      HPV) could be an alternative to the Pap smear, but costs, sampling methods and
      transport issues hamper its wide use. Our objective was to compare diagnostic
      accuracy of 2 vaginal self-collection methods, a dry swab (vsc-DRY) or swab in
      liquid medium (vsc-LIQ), for detecting HR-HPV cervical infection assessed by a
      cervical clinician-collected sample in liquid medium (ccc-LIQ). METHODS: Women 20
      to 65 years attending a Pap smear were recruited between September, 2009 and
      March, 2011. Each sample (3 per woman) underwent HPV DNA testing. Samples were
      classified as HR-HPV+ with detection of at least one HR-HPV or probable HR-HPV
      type. RESULTS: Of 734 women included, 722 had complete HPV data. HR-HPV was
      detected in 20.9% of ccc-LIQ samples. Estimated sensitivity and specificity to
      detect HR-HPV in vsc-DRY samples were 88.7% and 92.5%, respectively, and in vsc
      LIQ samples, 87.4% and 90.9%. Cytology findings were abnormal for 79 women
      (10.9%): among 27 samples of low-grade squamous intraepithelial lesions, 25 were
      HR-HPV+ in vsc-DRY, vsc-LIQ and ccc-LIQ samples. Among 6 samples of high-grade
      squamous intraepithelial lesions, all were HR-HPV+ in vsc-DRY samples, 1 was HR
      HPV- in vsc-LIQ samples and 1 was HR-HPV- in ccc-LIQ samples. CONCLUSIONS:
      Vaginal self-sampling with a dry swab is accurate to detect HR-HPV infection as
      compared with cervical clinician-collection and accurate as compared with
      cytology results. This cheap and easy-to-ship sampling method could be widely
      used in a cervical cancer screening program.

PMID- 24905775
TI  - Racial disparity in the 30-day morbidity and mortality after surgery for
      endometrial cancer.
AB  - OBJECTIVES: To examine postoperative 30-day morbidity and mortality in African
      American (AA) compared to white patients (W) with endometrial cancer (EC).
      METHODS: Patients with EC were identified from the American College of Surgeons
      National Surgical Quality Improvement Program from 2005 to 2011. AA and W
      subgroups were studied. Multivariable logistic regression models were performed.
      RESULTS: Of 3248 patients, 2899 (89%) W and 349 (11%) AA were identified. AA were
      more likely to have diabetes, hypertension, ascites, neurologic morbidities,
      weight loss, non-independent functional status, higher ASA class, higher serum
      creatinine >= 2 mg/dl, hypoalbuminemia and anemia. Laparoscopic surgery was
      performed less frequently in AA than W (41.4% vs. 50.3%, p<0.001). AA had a
      significantly higher risk of postoperative complications than W (21% vs. 12%,
      p<0.001) including surgical (17% vs. 10%, p<0.001) and non-surgical complications
      (7% vs. 4%, p=0.022). Mean length of hospital stay and operative time were longer
      in AA than W but there was no difference in surgical re-exploration. In
      multivariable model after adjustment for confounders including surgical
      complexity and associated morbidities, AA race was not an independent predictor
      of "any postoperative complications" for both laparotomy group (OR 1.1, 95% CI
      0.73-1.61, p=0.65) and laparoscopic group (OR 1.43, 95% CI 0.80-2.45, p=0.21). No
      difference in 30-day mortality was found between AA and W (1% vs. 1%, p=0.11).
      CONCLUSIONS: AA patients with EC have more preoperative morbidities,
      postoperative complications and were less likely to undergo minimally invasive
      surgery. However, AA race was not an independent predictor of poor 30-day
      outcomes after controlling for other confounders.

PMID- 24905774
TI  - Growth factor progranulin contributes to cervical cancer cell proliferation and
      transformation in vivo and in vitro.
AB  - OBJECTIVE: The growth factor progranulin (PGRN) is overexpressed in a number of
      tumors. We aimed to investigate the expression and role of PGRN in cervical
      cancer tumorigenesis. METHODS: PGRN expression and secretion was assessed in
      cells and normal and cancerous cervical tissues by Western blot analysis, ELISA
      or immunohistochemistry. The role of PGRN in cervical carcinogenesis was explored
      by cell-proliferation, colony-formation and tumor-growth assays. We assessed the
      role of PGRN-mediated signaling in the cervical cell with specific inhibitors.
      RESULTS: PGRN expression was upregulated in cervical cancer cell lines and
      tissue. PGRN promoted the transformation of human cervical mucosa epithelial H8
      cells in vitro and tumor formation in vivo. Knockdown of PGRN expression in
      cervical cancer cells in vivo decreased cell proliferation and slowed tumor
      growth. PGRN stimulated cervical cell proliferation, and transformation was
      mediated, at least in part, by Akt and Erk signaling. CONCLUSIONS: PGRN is
      overexpressed in cervical cancer and promotes the malignant growth and
      transformation of cervical cells. Therefore, PGRN plays a critical role in
      carcinogenesis of cervical cancer and shows promise for therapeutic strategies
      for cervical cancer.

PMID- 24905776
TI  - A co-delivery system based on paclitaxel grafted mPEG-b-PLG loaded with
      doxorubicin: preparation, in vitro and in vivo evaluation.
AB  - Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin
      hydrochloride (DOX.HCl) based on methoxypoly(ethylene glycol)-block-poly(L
      glutamic acid) (mPEG-b-PLG) for cancer treatment. PTX was grafted to the mPEG-b
      PLG by esterification to give mPEG-b-PLG-g-PTX. DOX.HCl was encapsulated via
      electrostatic interaction and hydrophobic stack between the DOX.HCl and mPEG-b
      PLG-g-PTX in aqueous solution. The release rate of DOX.HCl from the drug-loaded
      nanoparticles (mPEG-b-PLG-g-PTX-DOX) was slow at blood pH (pH 7.4), but obviously
      increased at endosome pH (pH 5.4). The mPEG-b-PLG-g-PTX-DOX exhibited slight
      synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer
      cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG-b
      PLG-g-PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a
      95.5% tumor-suppression-rate which was significantly higher than those of related
      single anticancer agents such as free DOX.HCl and mPEG-b-PLG-g-PTX. These results
      indicated that the mPEG-b-PLG-g-PTX-DOX would have great potential in cancer
      therapy.

PMID- 24905777
TI  - MUC1 aptamer conjugated to chitosan nanoparticles, an efficient targeted carrier
      designed for anticancer SN38 delivery.
AB  - Molecularly targeted therapy is of great interest for diagnosis and treatment of
      cancerous cells due to its low toxicity for normal cells. In this study, chitosan
      was utilized as a promising carrier for delivery, and aptamer (Apt) was employed
      for active targeting of SN38 to colon cancer. SN38 cannot be used clinically due
      to its poor solubility and high toxicity. Developing nanoparticles (NPs) of drug
      polymer conjugates can be a good candidate for overcoming such problems. N
      Carboxyethyl chitosan ester (CS-EA) was synthesized as an intermediate for
      conjugation of SN38 to chitosan. MUC1 DNA aptamer with 5'-NH2 functional group
      was conjugated to the self-assembled conjugate as a targeting agent. Prepared NPs
      had smooth and spherical morphology with 200 nm particle size. Conjugation of
      aptamer was confirmed by gel electrophoresis. In vitro cytotoxicity of NPs was
      assessed by HT-29 as MUC1 positive cell line through MTT assay. Aptamer
      conjugated NPs (Apt NPs) were more toxic than non-targeted NPs, however they were
      as toxic as free drug. Cellular uptake and targeting ability of prepared NPs were
      also confirmed via confocal microscopy. As a conclusion, prepared CS-SN38-Apt NPs
      can increase efficacy of drug SN38 through increasing solubility and specific
      delivery to the target tissue.

PMID- 24905778
TI  - Lack of association of joint hypermobility with urinary incontinence subtypes and
      pelvic organ prolapse.
AB  - OBJECTIVE: To test the hypothesis that joint hypermobility (JHM) is associated
      with specific urinary incontinence (UI) subtypes and uterovaginal prolapse.
      PATIENTS AND METHODS: In all, 270 women scheduled to undergo urodynamic
      investigations were invited to self-complete a validated five-item JHM
      questionnaire. Women underwent history taking, symptoms assessing via the King's
      Health Questionnaire and clinical examination using the Pelvic Organ Prolapse
      Quantification system. Associations between JHM and pelvic floor disorders in
      univariate and multivariate ordinal regression were reported using odds ratios
      (ORs) and 95% confidence intervals (CIs). RESULTS: The prevalence of JHM was
      31.1%. JHM had a negative association with age (OR 0.98/year, P = 0.04). There
      was no association between JHM and either urodynamic (P = 0.41), or symptomatic
      stress UI (P = 0.48). Nor was there association with detrusor overactivity or
      symptomatic urgency UI. Multivariate ordinal regression of JHM with maximum
      prolapse stage, adjusting for age, showed a significant relationship (OR
      1.26/stage, 95% CI 1.06-1.46, P < 0.05). CONCLUSION: Although JHM is highly
      prevalent amongst women with lower urinary tract symptoms (LUTS), there is no
      strong association of JHM with any UI subtype. There is a trend towards higher
      prolapse staging in women with JHM, which becomes significant only after
      adjustment for the confounding negative association between age and JHM.

PMID- 24905779
TI  - Molecular robots with sensors and intelligence.
AB  - CONSPECTUS: What we can call a molecular robot is a set of molecular devices such
      as sensors, logic gates, and actuators integrated into a consistent system. The
      molecular robot is supposed to react autonomously to its environment by receiving
      molecular signals and making decisions by molecular computation. Building such a
      system has long been a dream of scientists; however, despite extensive efforts,
      systems having all three functions (sensing, computation, and actuation) have not
      been realized yet. This Account introduces an ongoing research project that
      focuses on the development of molecular robotics funded by MEXT (Ministry of
      Education, Culture, Sports, Science and Technology, Japan). This 5 year project
      started in July 2012 and is titled "Development of Molecular Robots Equipped with
      Sensors and Intelligence". The major issues in the field of molecular robotics
      all correspond to a feedback (i.e., plan-do-see) cycle of a robotic system. More
      specifically, these issues are (1) developing molecular sensors capable of
      handling a wide array of signals, (2) developing amplification methods of signals
      to drive molecular computing devices, (3) accelerating molecular computing, (4)
      developing actuators that are controllable by molecular computers, and (5)
      providing bodies of molecular robots encapsulating the above molecular devices,
      which implement the conformational changes and locomotion of the robots. In this
      Account, the latest contributions to the project are reported. There are four
      research teams in the project that specialize on sensing, intelligence, amoeba
      like actuation, and slime-like actuation, respectively. The molecular sensor team
      is focusing on the development of molecular sensors that can handle a variety of
      signals. This team is also investigating methods to amplify signals from the
      molecular sensors. The molecular intelligence team is developing molecular
      computers and is currently focusing on a new photochemical technology for
      accelerating DNA-based computations. They also introduce novel computational
      models behind various kinds of molecular computers necessary for designing such
      computers. The amoeba robot team aims at constructing amoeba-like robots. The
      team is trying to incorporate motor proteins, including kinesin and microtubules
      (MTs), for use as actuators implemented in a liposomal compartment as a robot
      body. They are also developing a methodology to link DNA-based computation and
      molecular motor control. The slime robot team focuses on the development of slime
      like robots. The team is evaluating various gels, including DNA gel and BZ gel,
      for use as actuators, as well as the body material to disperse various molecular
      devices in it. They also try to control the gel actuators by DNA signals coming
      from molecular computers.

PMID- 24905781
TI  - Interactive features of proteins composing eukaryotic circadian clocks.
AB  - Research into the molecular mechanisms of eukaryotic circadian clocks has
      proceeded at an electrifying pace. In this review, we discuss advances in our
      understanding of the structures of central molecular players in the timing
      oscillators of fungi, insects, and mammals. A series of clock protein structures
      demonstrate that the PAS (Per/Arnt/Sim) domain has been used with great variation
      to formulate the transcriptional activators and repressors of the clock. We
      discuss how posttranslational modifications and external cues, such as light,
      affect the conformation and function of core clock components. Recent
      breakthroughs have also revealed novel interactions among clock proteins and new
      partners that couple the clock to metabolic and developmental pathways. Overall,
      a picture of clock function has emerged wherein conserved motifs and structural
      platforms have been elaborated into a highly dynamic collection of interacting
      molecules that undergo orchestrated changes in chemical structure, conformational
      state, and partners. 

PMID- 24905780
TI  - Lead exposure, B vitamins, and plasma homocysteine in men 55 years of age and
      older: the VA normative aging study.
AB  - BACKGROUND: Lead (Pb) exposure may influence the plasma concentration of
      homocysteine, a one-carbon metabolite associated with cardiovascular and
      neurodegenerative diseases. Little is known about the associations between Pb and
      homocysteine over time, or the potential influence of dietary factors.
      OBJECTIVES: We examined the longitudinal association of recent and cumulative Pb
      exposure with homocysteine concentrations and the potential modifying effect of
      dietary nutrients involved in one-carbon metabolism. METHODS: In a subcohort of
      the Veterans Affairs (VA) Normative Aging Study (1,056 men with 2,301 total
      observations between 1993 and 2011), we used mixed-effects models to estimate
      differences in repeated measures of total plasma homocysteine across
      concentrations of Pb in blood and tibia bone, assessing recent and cumulative Pb
      exposure, respectively. We also assessed effect modification by dietary intake
      and plasma concentrations of folate, vitamin B6, and vitamin B12. RESULTS: An
      interquartile range (IQR) increment in blood Pb (3 MUg/dL) was associated with a
      6.3% higher homocysteine concentration (95% CI: 4.8, 7.8%). An IQR increment in
      tibia bone Pb (14 MUg/g) was associated with a 3.7% higher homocysteine (95% CI:
      1.6, 5.6%), which was attenuated to 1.5% (95% CI: -0.5, 3.6%) after adjusting for
      blood Pb. For comparison, a 5-year increase in time from baseline was associated
      with a 5.7% increase in homocysteine (95% CI: 4.3, 7.1%). The association between
      blood Pb and homocysteine was significantly stronger among participants with
      estimated dietary intakes of vitamin B6 and folate below (vs. above) the study
      population medians, which were similar to the U.S. recommended dietary allowance
      intakes. CONCLUSIONS: Pb exposure was positively associated with plasma
      homocysteine concentration. This association was stronger among men with below
      median dietary intakes of vitamins B6 and folate. These findings suggest that
      increasing intake of folate and B6 might reduce Pb-associated increases in
      homocysteine, a risk factor for cardiovascular disease and neurodegeneration.

PMID- 24905783
TI  - Activity-based profiling of proteases.
AB  - Proteolytic enzymes are key signaling molecules in both normal physiological
      processes and various diseases. After synthesis, protease activity is tightly
      controlled. Consequently, levels of protease messenger RNA and protein often are
      not good indicators of total protease activity. To more accurately assign
      function to new proteases, investigators require methods that can be used to
      detect and quantify proteolysis. In this review, we describe basic principles,
      recent advances, and applications of biochemical methods to track protease
      activity, with an emphasis on the use of activity-based probes (ABPs) to detect
      protease activity. We describe ABP design principles and use case studies to
      illustrate the application of ABPs to protease enzymology, discovery and
      development of protease-targeted drugs, and detection and validation of proteases
      as biomarkers. 

PMID- 24905784
TI  - Bringing dynamic molecular machines into focus by methyl-TROSY NMR.
AB  - Large macromolecular assemblies, so-called molecular machines, are critical to
      ensuring proper cellular function. Understanding how proper function is achieved
      at the atomic level is crucial to advancing multiple avenues of biomedical
      research. Biophysical studies often include X-ray diffraction and cryo-electron
      microscopy, providing detailed structural descriptions of these machines.
      However, their inherent flexibility has complicated an understanding of the
      relation between structure and function. Solution NMR spectroscopy is well suited
      to the study of such dynamic complexes, and continued developments have increased
      size boundaries; insights into function have been obtained for complexes with
      masses as large as 1 MDa. We highlight methyl-TROSY (transverse relaxation
      optimized spectroscopy) NMR, which enables the study of such large systems, and
      include examples of applications to several cellular machines. We show how this
      emerging technique contributes to an understanding of cellular function and the
      role of molecular plasticity in regulating an array of biochemical activities. 

PMID- 24905785
TI  - Enzyme inhibitor discovery by activity-based protein profiling.
AB  - Eukaryotic and prokaryotic organisms possess huge numbers of uncharacterized
      enzymes. Selective inhibitors offer powerful probes for assigning functions to
      enzymes in native biological systems. Here, we discuss how the chemical proteomic
      platform activity-based protein profiling (ABPP) can be implemented to discover
      selective and in vivo-active inhibitors for enzymes. We further describe how
      these inhibitors have been used to delineate the biochemical and cellular
      functions of enzymes, leading to the discovery of metabolic and signaling
      pathways that make important contributions to human physiology and disease. These
      studies demonstrate the value of selective chemical probes as drivers of
      biological inquiry. 

PMID- 24905782
TI  - Metabolic compensation and circadian resilience in prokaryotic cyanobacteria.
AB  - For a biological oscillator to function as a circadian pacemaker that confers a
      fitness advantage, its timing functions must be stable in response to
      environmental and metabolic fluctuations. One such stability enhancer,
      temperature compensation, has long been a defining characteristic of these
      timekeepers. However, an accurate biological timekeeper must also resist changes
      in metabolism, and this review suggests that temperature compensation is actually
      a subset of a larger phenomenon, namely metabolic compensation, which maintains
      the frequency of circadian oscillators in response to a host of factors that
      impinge on metabolism and would otherwise destabilize these clocks. The circadian
      system of prokaryotic cyanobacteria is an illustrative model because it is
      composed of transcriptional and nontranscriptional oscillators that are coupled
      to promote resilience. Moreover, the cyanobacterial circadian program regulates
      gene activity and metabolic pathways, and it can be manipulated to improve the
      expression of bioproducts that have practical value. 

PMID- 24905786
TI  - Histone chaperones: assisting histone traffic and nucleosome dynamics.
AB  - The functional organization of eukaryotic DNA into chromatin uses histones as
      components of its building block, the nucleosome. Histone chaperones, which are
      proteins that escort histones throughout their cellular life, are key actors in
      all facets of histone metabolism; they regulate the supply and dynamics of
      histones at chromatin for its assembly and disassembly. Histone chaperones can
      also participate in the distribution of histone variants, thereby defining
      distinct chromatin landscapes of importance for genome function, stability, and
      cell identity. Here, we discuss our current knowledge of the known histone
      chaperones and their histone partners, focusing on histone H3 and its variants.
      We then place them into an escort network that distributes these histones in
      various deposition pathways. Through their distinct interfaces, we show how they
      affect dynamics during DNA replication, DNA damage, and transcription, and how
      they maintain genome integrity. Finally, we discuss the importance of histone
      chaperones during development and describe how misregulation of the histone flow
      can link to disease. 

PMID- 24905788
TI  - PTEN.
AB  - The importance of PTEN in cellular function is underscored by the frequency of
      its deregulation in cancer. PTEN tumor-suppressor activity depends largely on its
      lipid phosphatase activity, which opposes PI3K/AKT activation. As such, PTEN
      regulates many cellular processes, including proliferation, survival, energy
      metabolism, cellular architecture, and motility. More than a decade of research
      has expanded our knowledge about how PTEN is controlled at the transcriptional
      level as well as by numerous posttranscriptional modifications that regulate its
      enzymatic activity, protein stability, and cellular location. Although the role
      of PTEN in cancers has long been appreciated, it is also emerging as an important
      factor in other diseases, such as diabetes and autism spectrum disorders. Our
      understanding of PTEN function and regulation will hopefully translate into
      improved prognosis and treatment for patients suffering from these ailments. 

PMID- 24905789
TI  - A longitudinal high-risk study of adolescent anxiety, depression and parent
      severity on the developmental course of risk-adjustment.
AB  - BACKGROUND: Adolescence is associated with developments in the reward system and
      increased rates of emotional disorders. Familial risk for depression may be
      associated with disruptions in the reward system. However, it is unclear how
      symptoms of depression and anxiety influence the development of reward-processing
      over adolescence and whether variation in the severity of parental depression is
      associated with hyposensitivity to reward in a high-risk sample. METHODS: We
      focused on risk-adjustment (adjusting decisions about reward according to the
      probability of obtaining reward) as this was hypothesized to improve over
      adolescence. In a one-year longitudinal sample (N = 197) of adolescent offspring
      of depressed parents, we examined how symptoms of depression and anxiety
      (generalized anxiety and social anxiety) influenced the development of risk
      adjustment. We also examined how parental depression severity influenced
      adolescent risk-adjustment. RESULTS: Risk-adjustment improved over the course of
      the study indicating improved adjustment of reward-seeking to shifting
      contingencies. Depressive symptoms were associated with decreases in risk
      adjustment over time while social anxiety symptoms were associated with increases
      in risk-adjustment over time. Specifically, depression was associated with
      reductions in reward-seeking at favourable reward probabilities only, whereas
      social anxiety (but not generalized anxiety) led to reductions in reward-seeking
      at low reward probabilities only. Parent depression severity was associated with
      lowered risk-adjustment in offspring and also influenced the longitudinal
      relationship between risk-adjustment and offspring depression. CONCLUSIONS:
      Anxiety and depression distinctly alter the pattern of longitudinal change in
      reward-processing. Severity of parent depression was associated with alterations
      in adolescent offspring reward-processing in a high-risk sample.

PMID- 24905790
TI  - Scimitar syndrome in a case with VACTERL association.
AB  - VACTERL association and Scimitar syndrome are rare congenital diseases. In this
      study, we report on a neonate with prenatal suspicion of VACTERL association and
      small left-sided cardiac structures, which, only on postnatal angiography, could
      be revealed to be part of a Scimitar syndrome. As this is the second reported
      case of VACTERL association and Scimitar syndrome, the presence of Scimitar
      syndrome should be considered in the prenatal and postnatal evaluation of VACTERL
      association. 

PMID- 24905791
TI  - HERFD-XAS and valence-to-core-XES: new tools to push the limits in research with
      hard X-rays?
AB  - In this perspective, the HERFD-XANES (high energy resolution fluorescence
      detected X-ray absorption near edge structure) and Kbeta2,5- or V2C-XES (valence
      to-core X-ray emission spectroscopy) methods are discussed as new and powerful
      tools for chemical research with hard X-rays. This includes a brief survey of the
      underlying physical processes and the introduction of experimental issues. The
      potential of both methods to overcome limitations of conventional XAS (X-ray
      absorption spectroscopy) and to push the limits for obtaining new information
      about the electronic and geometric structures of metal centers, in the solid
      state structure or heterogeneous catalysts, but also in metal complexes and
      homogeneous catalysts, is discussed by presenting a survey of representative
      references and recent own studies, rounded off by a conclusion and outlook. 

PMID- 24905793
TI  - Abstracts of the Eighteenth International Congress of Parkinson's Disease and
      Movement Disorders, June 8-12, 2014, Stockholm, Sweden.

PMID- 24905792
TI  - Laparoscopic splenectomy for primary immune thrombocytopenia: clinical outcome
      and prognostic factors.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is considered the standard treatment
      for patients with refractory primary immune thrombocytopenia (ITP). PATIENTS AND
      METHODS: All patients with ITP who underwent LS during the last 17 years and who
      had a minimum follow-up of 1 year were included. Several perioperative variables
      such as age, platelet count, and duration of preoperative therapy were recorded
      and analyzed, looking for potential predictive variables of clinical response.
      RESULTS: In total, 150 patients were included: 108 (72%) women and 42 (28%) men,
      with a mean age of 37.3+/-15.8 years. In the evaluation 1 year after surgery, 133
      (88.7%) patients had achieved complete response, 4 (2.7%) had a response, and in
      13 (8.6%) there was no response. None of the analyzed preoperative variables was
      identified as a predictive factor of response at 1 year. Immediate responders
      after surgery (>=150,000 platelets/mL during the first week) had a higher
      platelet count and rate of complete response at 1 year (94.2%). CONCLUSIONS: LS
      has a high success rate in patients with refractory ITP. Potential predictive
      indicators of success remain to be determined.

PMID- 24905787
TI  - Mechanism and function of oxidative reversal of DNA and RNA methylation.
AB  - The importance of eukaryotic DNA methylation [5-methylcytosine (5mC)] in
      transcriptional regulation and development was first suggested almost 40 years
      ago. However, the molecular mechanism underlying the dynamic nature of this
      epigenetic mark was not understood until recently, following the discovery that
      the TET proteins, a family of AlkB-like Fe(II)/alpha-ketoglutarate-dependent
      dioxygenases, can oxidize 5mC to generate 5-hydroxymethylcytosine (5hmC), 5
      formylcytosine (5fC), and 5-carboxylcytosine (5caC). Since then, several
      mechanisms that are responsible for processing oxidized 5mC derivatives to
      achieve DNA demethylation have emerged. Our biochemical understanding of the DNA
      demethylation process has prompted new investigations into the biological
      functions of DNA demethylation. Characterization of two additional AlkB family
      proteins, FTO and ALKBH5, showed that they possess demethylase activity toward
      N(6)-methyladenosine (m(6)A) in RNA, indicating that members of this subfamily of
      dioxygenases have a general function in demethylating nucleic acids. In this
      review, we discuss recent advances in this emerging field, focusing on the
      mechanism and function of TET-mediated DNA demethylation. 

PMID- 24905794
TI  - Case of cholangiocellular carcinoma in a patient with glycogen storage disease
      type Ia.
AB  - Glycogen storage disease (GSD) type Ia is caused by a deficiency in glucose-6
      phosphatase. Long-term complications, including renal disease, gout, osteoporosis
      and pulmonary hypertension, develop in patients with GSD type Ia. In the second
      or third decade, 22-75% of GSD type Ia patients develop hepatocellular adenoma
      (HCA). In some of these patients, the HCA evolves into hepatocellular carcinoma.
      However, little is known about GSD type Ia patients with HCA who develop
      cholangiocellular carcinoma (CCC). Here, we report for the first time, a patient
      with GSD type Ia with HCA, in whom intrahepatic CCC was developed. 

PMID- 24905795
TI  - Two-year safety and effectiveness of the platinum chromium everolimus-eluting
      stent for the treatment of small vessels and longer lesions.
AB  - OBJECTIVES: To report 1- and 2-year clinical outcomes of patients receiving
      platinum chromium everolimus-eluting stents (PtCr-EES) in the prospective, single
      arm PLATINUM small vessel (SV) and long lesion (LL) studies. BACKGROUND: Small
      vessel diameter and long lesion length are independently associated with
      increased risk of adverse cardiac events after drug-eluting stent implantation.
      METHODS: The PLATINUM SV study enrolled 94 patients with coronary artery lesions
      in vessels >=2.25 mm to <2.50 mm in diameter and <=28 mm in length. The PLATINUM
      LL study enrolled 102 patients with lesions >24 to <=34 mm long in vessels >=2.50
      to <=4.25 mm in diameter. The primary endpoint for both studies was target lesion
      failure (TLF) at 1 year compared to a prespecified performance goal based on
      outcomes with the TAXUS Express paclitaxel-eluting stent in small vessels and
      long lesions. RESULTS: One-year TLF rates with the PtCr-EES were significantly (P
      < 0.001) lower than the predetermined performance goals: 2.4% versus 21.1% in the
      SV cohort and 3.2% versus 19.4% in the LL cohort. Cumulative rates of TLF to 2
      years were 4.7% in the SV cohort and 8.8% in the LL cohort. No myocardial
      infarction or ARC definite/probable stent thromboses occurred in either cohort
      through 2-year follow-up. CONCLUSIONS: The clinical efficacy and safety outcomes
      observed in these small vessel and long lesion cohorts support the use of the
      PtCr-EES in the treatment of small diameter vessels and long lesions.

PMID- 24905797
TI  - Cation- and anion-exchanges induce multiple distinct rearrangements within
      metallosupramolecular architectures.
AB  - Different anionic templates act to give rise to four distinct Cd(II)-based
      architectures: a Cd2L3 helicate, a Cd8L12 distorted cuboid, a Cd10L15 pentagonal
      prism, and a Cd12L18 hexagonal prism, which respond to both anionic and cationic
      components. Interconversions between architectures are driven by the addition of
      anions that bind more strongly within a given product framework. The addition of
      Fe(II) prompted metal exchange and transformation to a Fe4L6 tetrahedron or a
      Fe10L15 pentagonal prism, depending on the anionic templates present. The
      equilibrium between the Cd12L18 prism and the Cd2L3 triple helicate displayed
      concentration dependence, with higher concentrations favoring the prism. The
      Cd12L18 structure serves as an intermediate en route to a hexafluoroarsenate
      templated Cd10L15 complex, whereby the structural features of the hexagonal prism
      preorganize the system to form the structurally related pentagonal prism. In
      addition to the interconversion pathways investigated, we also report the single
      crystal X-ray structure of bifluoride encapsulated within a Cd10L15 complex and
      report solution state data for J-coupling through a CH...F(-) hydrogen bond
      indicating the strength of these interactions in solution. 

PMID- 24905796
TI  - A new approach for pancreatic tissue engineering: human endometrial stem cells
      encapsulated in fibrin gel can differentiate to pancreatic islet beta-cell.
AB  - Metabolic diabetes mellitus as the most serious and prevalent metabolic disease
      in the world has various complications. The most effective treatment of type I
      diabetes seems to be islet cell transplantation. Shortage of donors and difficult
      procedures and high rate of rejection have always restricted this approach.
      Tissue engineering is a novel effective solution to many medical problems such as
      diabetes. Endometrial mesenchymal stem cells as a lineage which have the
      potential to differentiate to mesodermal and endodermal tissues seem to be
      suitable for this purpose. Fibrin hydrogel with a high degree of biocompatibility
      and specific properties making it similar to normal pancreas seems to be an ideal
      scaffold. After successfully isolating stem cells (hEnSCs) from human
      endometrium, a three-step protocol was used to differentiate them into pancreatic
      beta cells. Fibrin was used as 3D scaffold. After 2 weeks, cells formed clusters
      like islets cells, and secretion of insulin was measured by chemiluminescence.
      PDX1, proinsulin, and c-peptide as special markers of beta cells were detected by
      immunofluorescence. Expression of glucagon, PDX1, and insulin genes in mRNA level
      was detected by Real time PCR and gel electrophoresis. The former showed higher
      levels of gene expression in 3D cultures. SEM analysis showed good integrity
      between cells and scaffold. No toxicity was detected with fibrin scaffold by MTT
      assay. 

PMID- 24905798
TI  - Monitoring the brain: processed electroencephalogram and peri-operative outcomes.
AB  - Although the brain is the target organ of general anaesthesia, the utility of
      intra-operative brain monitoring remains controversial. Ideally, the
      incorporation of brain monitoring into routine practice would promote the
      maintenance of an optimal depth of anaesthesia, with an ultimate goal of avoiding
      the negative outcomes that have been associated with inadequate or excessive
      anaesthesia. A variety of processed electroencephalogram devices exist, of which
      the bispectral index is the most widely used, particularly in the research
      setting. Whether such devices prove to be useful will depend not only on their
      ability to influence anaesthetic management but also on whether the changes they
      promote can actually affect clinically important outcomes. This review highlights
      the evidence for the role of bispectral index monitoring, in particular, in
      guiding anaesthetic management and influencing clinical outcomes, specifically
      intra-operative awareness, measures of early recovery, mortality and
      neurocognitive outcomes. 

PMID- 24905799
TI  - Measuring lipid packing of model and cellular membranes with environment
      sensitive probes.
AB  - The extent of lipid packing is one of the key physicochemical features of
      biological membranes and is involved in many membrane processes. Polarity
      sensitive fluorescent probes are commonly used tools to measure membrane lipid
      packing in both artificial and biological membranes. In this paper, we have
      systematically compared eight different probes to measure membrane lipid
      ordering. We investigated how these probes behave in small unilamellar liposomes,
      phase-separated giant unilamellar vesicles, cell-derived giant plasma membrane
      vesicles, and live cells. We have tested the order sensitivity of a variety of
      measurable parameters, including generalized polarization, peak shift, or
      intensity shift. We also investigated internalization and photostability of the
      probes to assess probe potential for time-lapse live cell imaging. These results
      provide a catalogue of properties to facilitate the choice of probe according to
      need. 

PMID- 24905800
TI  - Children's Physical Activity While Gardening: Development of a Valid and Reliable
      Direct Observation Tool.
AB  - BACKGROUND: Gardens are a promising intervention to promote physical activity
      (PA) and foster health. However, because of the unique characteristics of
      gardening, no extant tool can capture PA, postures, and motions that take place
      in a garden. METHODS: The Physical Activity Research and Assessment tool for
      Garden Observation (PARAGON) was developed to assess children's PA levels, tasks,
      postures, and motions, associations, and interactions while gardening. PARAGON
      uses momentary time sampling in which a trained observer watches a focal child
      for 15 seconds and then records behavior for 15 seconds. Sixty-five children (38
      girls, 27 boys) at 4 elementary schools in New York State were observed over 8
      days. During the observation, children simultaneously wore Actigraph GT3X+
      accelerometers. RESULTS: The overall interrater reliability was 88% agreement,
      and Ebel was .97. Percent agreement values for activity level (93%), garden tasks
      (93%), motions (80%), associations (95%), and interactions (91%) also met
      acceptable criteria. Validity was established by previously validated PA codes
      and by expected convergent validity with accelerometry. CONCLUSIONS: PARAGON is a
      valid and reliable observation tool for assessing children's PA in the context of
      gardening.

PMID- 24905801
TI  - Managing lung cancer in high-risk patients: what to consider.
AB  - Lung cancer patients with medical comorbidity are a challenge for care providers.
      As with other solid tumors, treatment is stage dependent; but a critical
      difference is the invasive nature of lung resections and the resulting importance
      of surgical risk stratification for treatment of early stage disease. External
      beam radiation was considered the only treatment option for early stage disease
      in non-operative candidates 10-15 years ago. With recent advances in image-guided
      technologies, robotics, and the resurgence in interest of sublobar resection
      there are now numerous treatment options which offer excellent local control and
      reasonable short and long term survival. Extensive work has been done to clarify
      interventional risk, and accurately describe anticipated outcomes of these varied
      treatments in the high risk population. The aim of this article is to review
      recent literature and provide a better understanding of the considerations used
      in the management of these patients in the current era. 

PMID- 24905802
TI  - 2014 Presidential Address: the power of the pharmacy family.

PMID- 24905803
TI  - Tim-3 polymorphism downregulates gene expression and is involved in the
      susceptibility to ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disorder primarily
      affecting the sacroiliac joints and the spine. T-cell immunoglobulin- and mucin
      domain-containing molecule 3 (TIM-3) has been established as a negative
      regulatory molecule that plays a critical role in controlling inflammation.
      Studies have shown that polymorphisms in TIM-3 gene may be associated with
      inflammatory diseases. The current study investigated the association between
      polymorphisms in the TIM-3 gene and susceptibility to AS, and it examined the
      effects of these polymorphisms on gene expression. Two polymorphisms in TIM-3 
      574G/T and +4259T/G polymorphisms were identified by polymerase chain reaction
      restriction fragment length polymorphism in 282 AS patients and 298 healthy
      controls. Results showed that frequency of the TIM-3 -574GT genotype was
      significantly increased in cases than in controls (Odd ratio [OR]=2.50, 95%
      confidence interval [CI]: 1.39-4.48, p=0.002). Similarly, TIM-3 -574T allele
      revealed a positive association with the disease (OR=2.39, p=0.002). The TIM-3
      +4259T/G polymorphism did not show any correlation with AS. We further evaluated
      TIM-3 mRNA and protein levels in CD4(+) T cells, CD8(+) T cells, and monocytes
      from subjects carrying different TIM-3 genotypes. Results revealed that subjects
      carrying polymorphic -574GT genotype had significantly lower TIM-3 mRNA and
      protein levels in CD4(+) T cells, CD8(+) T cells, and monocytes than those with
      wild-type GG genotype. These data suggest that TIM-3 polymorphism is associated
      with increased susceptibility to AS possibly by downregulating gene expression. 

PMID- 24905807
TI  - Fitness Testing for Children: Let's Mount the Zebra!

PMID- 24905804
TI  - High-resolution molecular validation of self-renewal and spontaneous
      differentiation in clinical-grade adipose-tissue derived human mesenchymal stem
      cells.
AB  - Improving the effectiveness of adipose-tissue derived human mesenchymal
      stromal/stem cells (AMSCs) for skeletal therapies requires a detailed
      characterization of mechanisms supporting cell proliferation and multi-potency.
      We investigated the molecular phenotype of AMSCs that were either actively
      proliferating in platelet lysate or in a basal non-proliferative state. Flow
      cytometry combined with high-throughput RNA sequencing (RNASeq) and RT-qPCR
      analyses validate that AMSCs express classic mesenchymal cell surface markers
      (e.g., CD44, CD73/NT5E, CD90/THY1, and CD105/ENG). Expression of CD90 is
      selectively elevated at confluence. Self-renewing AMSCs express a standard cell
      cycle program that successively mediates DNA replication, chromatin packaging,
      cyto-architectural enlargement, and mitotic division. Confluent AMSCs
      preferentially express genes involved in extracellular matrix (ECM) formation and
      cellular communication. For example, cell cycle-related biomarkers (e.g., cyclins
      E2 and B2, transcription factor E2F1) and histone-related genes (e.g., H4, HINFP,
      NPAT) are elevated in proliferating AMSCs, while ECM genes are strongly
      upregulated (>10-fold) in quiescent AMSCs. AMSCs also express pluripotency genes
      (e.g., POU5F1, NANOG, KLF4) and early mesenchymal markers (e.g., NES, ACTA2)
      consistent with their multipotent phenotype. Strikingly, AMSCs modulate
      expression of WNT signaling components and switch production of WNT ligands (from
      WNT5A/WNT5B/WNT7B to WNT2/WNT2B), while upregulating WNT-related genes (WISP2,
      SFRP2, and SFRP4). Furthermore, post-proliferative AMSCs spontaneously express
      fibroblastic, osteogenic, chondrogenic, and adipogenic biomarkers when maintained
      in confluent cultures. Our findings validate the biological properties of self
      renewing and multi-potent AMSCs by providing high-resolution quality control data
      that support their clinical versatility.

PMID- 24905806
TI  - Interleukin 17A promotes gastric cancer invasiveness via NF-kappaB mediated
      matrix metalloproteinases 2 and 9 expression.
AB  - Interleukin 17A (IL-17A), as a pro-inflammatory cytokine, is involved in
      pathology of inflammatory diseases and tumor microenvironment. The aim of this
      study is to investigate the effect of IL-17A on the invasiveness of gastric
      cancer (GC). In the study, we found that IL-17A could promote the migration and
      invasion of GC cells. Furthermore, after treated with IL-17A, the expressions and
      activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated,
      while the expressions of TIMP-1 and TIMP-2 were downregulated. Moreover, the
      nuclear/overall fractions of p65 and p50 were dramatically elevated by IL-17A.
      Pretreatment with helenalin, a nuclear factor-kappaB (NF-kappaB) inhibitor, was
      proved to abolish the promoting effect of IL-17A on the invasion ability of GC
      cells and upregulation of MMP-2 and MMP-9. In conclusion, our findings
      illustrated that IL-17A could promote the invasion of GC cells by activating NF
      kappaB pathway, and subsequently upregulating the expression of MMP-2 and MMP-9.
      These results may lead to the identification of new diagnostic markers and
      therapeutic targets of GC. 

PMID- 24905805
TI  - Dynamic haematopoietic cell contribution to the developing and adult epicardium.
AB  - The epicardium is a cellular source with the potential to reconstitute lost
      cardiovascular tissue following myocardial infarction. Here we show that the
      adult epicardium contains a population of CD45+ haematopoietic cells (HCs), which
      are located proximal to coronary vessels and encased by extracellular matrix
      (ECM). This complex tertiary structure is established during the regenerative
      window between post-natal days 1 and 7. We show that these HCs proliferate within
      the first 24 h and are released between days 2 and 7 after myocardial infarction.
      The ECM subsequently reforms to encapsulate HCs after 21 days. Vav1-tdTomato
      labelling reveals an integral contribution of CD45+ HCs to the developing
      epicardium, which is not derived from the proepicardial organ. Transplantation
      experiments with either whole bone marrow or a Vav1+ subpopulation of cells
      confirm a contribution of HCs to the intact adult epicardium, which is elevated
      during the first 24 weeks of adult life but depleted in aged mice.

PMID- 24905809
TI  - A revisit to contingency table and tests of independence: bootstrap is preferred
      to Chi-square approximations as well as Fisher's exact test.
AB  - To test the mutual independence of two qualitative variables (or attributes), it
      is a common practice to follow the Chi-square tests (Pearson's as well as
      likelihood ratio test) based on data in the form of a contingency table. However,
      it should be noted that these popular Chi-square tests are asymptotic in nature
      and are useful when the cell frequencies are "not too small." In this article, we
      explore the accuracy of the Chi-square tests through an extensive simulation
      study and then propose their bootstrap versions that appear to work better than
      the asymptotic Chi-square tests. The bootstrap tests are useful even for small
      cell frequencies as they maintain the nominal level quite accurately. Also, the
      proposed bootstrap tests are more convenient than the Fisher's exact test which
      is often criticized for being too conservative. Finally, all test methods are
      applied to a few real-life datasets for demonstration purposes. 

PMID- 24905808
TI  - Australian wild rice reveals pre-domestication origin of polymorphism deserts in
      rice genome.
AB  - BACKGROUND: Rice is a major source of human food with a predominantly Asian
      production base. Domestication involved selection of traits that are desirable
      for agriculture and to human consumers. Wild relatives of crop plants are a
      source of useful variation which is of immense value for crop improvement.
      Australian wild rices have been isolated from the impacts of domestication in
      Asia and represents a source of novel diversity for global rice improvement.
      Oryza rufipogon is a perennial wild progenitor of cultivated rice. Oryza
      meridionalis is a related annual species in Australia. RESULTS: We have examined
      the sequence of the genomes of AA genome wild rices from Australia that are close
      relatives of cultivated rice through whole genome re-sequencing. Assembly of the
      resequencing data to the O. sativa ssp. japonica cv. Nipponbare shows that
      Australian wild rices possess 2.5 times more single nucleotide polymorphisms than
      in the Asian wild rice and cultivated O. sativa ssp. indica. Analysis of the
      genome of domesticated rice reveals regions of low diversity that show very
      little variation (polymorphism deserts). Both the perennial and annual wild rice
      from Australia show a high degree of conservation of sequence with that found in
      cultivated rice in the same 4.58 Mbp region on chromosome 5, which suggests that
      some of the 'polymorphism deserts' in this and other parts of the rice genome may
      have originated prior to domestication due to natural selection. CONCLUSIONS:
      Analysis of genes in the 'polymorphism deserts' indicates that this selection may
      have been due to biotic or abiotic stress in the environment of early rice
      relatives. Despite having closely related sequences in these genome regions, the
      Australian wild populations represent an invaluable source of diversity
      supporting rice food security.

PMID- 24905810
TI  - The tsunami's impact on mortality in a town severely damaged by the 2011 Great
      East Japan Earthquake.
AB  - This study identifies the relationship between tsunami damage and mortality
      through a demographic pyramid of a town severely damaged by the tsunami following
      the Great East Japan Earthquake of 11 March 2011. It uses cross-sectional data
      collection. Volunteers visited all households, including shelters, and asked
      residents about the whereabouts of family members and neighbours. The information
      was collated with lists of evacuees and the dead to confirm the whereabouts of
      all residents about 50 days after the disaster. Demographic pyramids for the
      whole population based on pre- and post-disaster data were drawn. In all, 1,412
      (8.8 per cent) were dead or missing, 60.2 per cent of whom were aged 65 and over
      and 37.5 per cent aged 75 and over, suggesting that the very old should be
      located beyond the reach of tsunamis. The mortality rate of children was lower
      than that in other studies, which may indicate the efficacy of disaster
      evacuation drills. 

PMID- 24905811
TI  - Multi-level functionality of social media in the aftermath of the Great East
      Japan Earthquake.
AB  - This study examines the multi-level functionalities of social media in the
      aftermath of the Great East Japan Earthquake of 11 March 2011. Based on a
      conceptual model of multi-level story flows of social media (Jung and Moro,
      2012), the study analyses the multiple functionalities that were ascribed to
      social media by individuals, organisations, and macro-level social systems
      (government and the mass media) after the earthquake. Based on survey data, a
      review of Twitter timelines and secondary sources, the authors derive five
      functionalities of social media: interpersonal communications with others (micro
      level); channels for local governments; organisations and local media (meso
      level); channels for mass media (macro level); information sharing and gathering
      (cross level); and direct channels between micro-/meso- and macro-level agents.
      The study sheds light on the future potential of social media in disaster
      situations and suggests how to design an effective communication network to
      prepare for emergency situations. 

PMID- 24905812
TI  - Relaying support in disaster-affected areas: the social implications of a 'pay-it
      forward' network.
AB  - When a disaster strikes a country, a temporary so-called post-disaster utopia
      emerges in which local residents help each other and outsiders support survivors
      and victims. However, this utopia does not last. Survivors are likely to have no
      chance to pay people back for the help they have received and thus return to
      their daily lives with a sense of debt. After the Great East Japan Earthquake the
      author motivated survivors of other disasters to help survivors in the Tohoku
      region in eastern Japan in return for the support they had received in the past.
      Two findings are revealed: firstly, this pay-it-forward support among disaster
      affected areas allows for intermittent rebuilding of the post-disaster utopia.
      Secondly, a theoretical examination of the network theory also suggests that the
      pay-it-forward network is likely to expand and cover the whole of society very
      quickly. The psychological and sociological implications of these findings are
      also discussed. 

PMID- 24905813
TI  - Post-tsunami recovery and reconstruction: governance issues and implications of
      the Great East Japan Earthquake.
AB  - Post-disaster governance is a popular discussion topic in disaster research, but
      in practice understanding of the issue is limited. This paper discusses recovery
      governance since the 2011 Japanese earthquake and tsunami, focusing on two
      dimensions: decentralisation and citizen participation in local governance.
      Regional Japan's socio-spatial vitality has been shrinking and weakening under
      the developmental state system. The 2011 disaster exposed vulnerabilities in the
      socio-political system. For a short time it appeared that local political space
      had been opened for alternative governance systems; however, only limited
      improvements have occurred in decentralisation reform and civic participation
      systems. Tsunami recovery was constrained and delayed by predisaster
      trajectories, although socio-spatial inequalities increased. The paper suggests
      the implications of this for the developmental state and argues that drastic
      action should be taken to rectify the faults of the socio-political system, to
      stop the disaster-affected area's decline, and to promote regional and community
      recovery. 

PMID- 24905814
TI  - Parenting in Fukushima City in the post-disaster period: short-term strategies
      and long-term perspectives.
AB  - Growing evidence indicates the adverse psychological and welfare consequences of
      nuclear power accidents particularly among parents of small children. However,
      little has been published about the public health experiences of and practical
      countermeasures to deal with such consequences for parents of small children in
      the aftermath of disasters. Based on our past research efforts to develop
      parenting support programmes in Fukushima City, we describe here the discussions
      and resulting strategies that developed from collaborative efforts between
      university researchers and public health nurses after the Fukushima nuclear plant
      accident caused by the Great East Japan Earthquake. The processes presented here
      may be useful to improve national and international preparedness to protect the
      health of parents and children in future nuclear disasters. 

PMID- 24905815
TI  - Disaster myths after the Great East Japan Disaster and the effects of information
      sources on belief in such myths.
AB  - This study examines how well disaster myths were rooted in Japanese people after
      the Great East Japan Disaster, as well as the effects of information sources on
      these misconceptions. Five common disaster myths are covered (panic,
      psychological shock, looting, increases in the crime rate, and material
      convergence), and information sources were divided into two types: public and
      private. Three hundred participants were asked how much credit they would give
      the five myths and which information sources they would rely on in post-disaster
      situations. The results found that, as in Western societies, these disaster myths
      do exist among Japanese people. Also, only public sources of disaster
      information, such as television and Internet news websites, had some effect on
      the degree of belief in disaster myths, while private sources, such as one's
      family, friends, and social networking sites, did not. Factors affecting the
      degree to which people believe in disaster myths are also discussed. 

PMID- 24905816
TI  - Applying the natural disasters vulnerability evaluation model to the March 2011
      north-east Japan earthquake and tsunami.
AB  - Natural hazards have a potentially large impact on economic growth, but measuring
      their economic impact is subject to a great deal of uncertainty. The central
      objective of this paper is to demonstrate a model--the natural disasters
      vulnerability evaluation (NDVE) model--that can be used to evaluate the impact of
      natural hazards on gross national product growth. The model is based on five
      basic indicators-natural hazards growth rates (alphai), the national natural
      hazards vulnerability rate (OmegaT), the natural disaster devastation magnitude
      rate (Pi), the economic desgrowth rate (i.e. shrinkage of the economy) (delta),
      and the NHV surface. In addition, we apply the NDVE model to the north-east Japan
      earthquake and tsunami of March 2011 to evaluate its impact on the Japanese
      economy.

PMID- 24905817
TI  - Synthesis, luminescence, and energy-transfer properties of beta
      Na2Ca4(PO4)2(SiO4):A (A = Eu(2+), Dy(3+), Ce(3+)/Tb(3+)) phosphors.
AB  - A series of beta-Na2Ca4(PO4)2(SiO4) (beta-NCPS):A (A = Eu(2+), Dy(3+),
      Ce(3+)/Tb(3+)) phosphors were prepared via a high-temperature solid-state
      reaction route. The X-ray diffraction, Fourier transform infrared,
      photoluminescence (PL), cathodoluminescence (CL) properties, fluorescent
      lifetimes, and absolute quantum yield were exploited to characterize the samples.
      Under UV radiation, the beta-NCPS:Eu(2+) phosphors present bright green
      emissions, and the beta-NCPS:Ce(3+) phosphors show strong blue emissions, which
      are attributed to their 4f(6)5d(1) -> 4f(7) and 5d-4f allowed transitions,
      respectively. The beta-NCPS:Ce(3+), Tb(3+) phosphors display intense tunable
      color from blue to green and high absolute quantum yields (81% for beta
      NCPS:0.12Ce(3+) and 83% for beta-NCPS:0.12Ce(3+), 0.08Tb(3+)) when excited at 365
      nm. Simultaneously, the energy transfer from Ce(3+) to Tb(3+) ions is deduced
      from the spectral overlap between Ce(3+) emission and Tb(3+) excitation spectra
      and demonstrated by the change of emission spectra and decay lifetimes. Moreover,
      the energy-transfer mechanism from Ce(3+) to Tb(3+) ions is confirmed to be
      exchange interaction according to the discussion of expression from Dexter and
      Reisfeld. Under a low-voltage electron-beam excitation, the beta-NCPS:A (A =
      Eu(2+), Dy(3+), Ce(3+)/Tb(3+)) phosphors exhibit their characteristic emissions,
      and the emission profiles of beta-NCPS:Ce(3+),Tb(3+) phosphors are obviously
      different from those of the PL spectra; this difference might be ascribed to
      their different luminescence mechanisms. These results in PL and CL properties
      suggest that beta-NCPS:A (A = Eu(2+), Dy(3+), Ce(3+)/Tb(3+)) phosphors are
      potential candidates for solid-state lighting and field-emission displays. 

PMID- 24905818
TI  - Multi-scale characterization of lyotropic liquid crystals using 2H and diffusion
      MRI with spatial resolution in three dimensions.
AB  - The ability of lyotropic liquid crystals to form intricate structures on a range
      of length scales can be utilized for the synthesis of structurally complex
      inorganic materials, as well as in devices for controlled drug delivery. Here we
      employ magnetic resonance imaging (MRI) for non-invasive characterization of nano
      , micro-, and millimeter scale structures in liquid crystals. The structure is
      mirrored in the translational and rotational motion of the water, which we assess
      by measuring spatially resolved self-diffusion tensors and 2H spectra. Our
      approach differs from previous works in that the MRI parameters are mapped with
      spatial resolution in all three dimensions, thus allowing for detailed studies of
      liquid crystals with complex millimeter-scale morphologies that are stable on the
      measurement time-scale of 10 hours. The 2H data conveys information on the
      nanometer-scale structure of the liquid crystalline phase, while the combination
      of diffusion and 2H data permits an estimate of the orientational distribution of
      micrometer-scale anisotropic domains. We study lamellar phases consisting of the
      nonionic surfactant C10E3 in 2H2O, and follow their structural equilibration
      after a temperature jump and the cessation of shear. Our experimental approach
      may be useful for detailed characterization of liquid crystalline materials with
      structures on multiple length scales, as well as for studying the mechanisms of
      phase transitions.

PMID- 24905819
TI  - Solvatochromism in a pyridinium cyclopentadienylide: insights from a sequential
      Car-Parrinello QM/MM and TD-DFT/semicontinuum approach.
AB  - Understanding the working mechanism and establishing structure-property
      relationships for optical probes is an essential step to develop design
      principles for novel molecular probes. Here we study optical properties of a
      small-sized dielectric probe, namely, 4-carbamido pyridinium cyclopentadienylide
      (CPYC) in benzene and in water solvents using a sequential approach. In
      particular, the structure modeling has been carried out using a Car-Parrinello
      hybrid QM/MM molecular dynamics approach, while the excitation energies were
      computed using time dependent density functional theory. To incorporate the
      solvent effect either a polarizable continuum model or a semicontinuum
      description was employed. The molecular dipole moment of CPYC in water is more
      than two times larger than in benzene solvent. The positive and negative charges
      tend to accumulate on pyridinium and cyclopentadienylide rings, respectively,
      with increasing solvent polarity. Significant solvent-induced geometrical changes
      have been reported in CPYC and this contributes to a significant red shift in
      spectra. Even though the absorption maxima for CPYC in benzene and water solvents
      were underestimated, the solvatochromic shift has been reproduced in good
      agreement with experiments. We also report that CPYC can be used as a two photon
      probe. 

PMID- 24905820
TI  - The chemical life(1).
AB  - You write this narrative autoethnography to open up a conversation about our
      chemical lives. You go through your day with chemical mindfulness, questioning
      taken-for-granted ideas about natural and artificial, healthy and unhealthy,
      dependency and addiction, trying to understand the chemical messages we consume
      through the experiences of everyday life. You reflect on how messages about
      chemicals influence and structure our lives and why some chemicals are celebrated
      and some are condemned. Using a second-person narrative voice, you show how the
      personal is relational and the chemical is cultural. You write because you seek a
      connection, a chemical bond. 

PMID- 24905821
TI  - Low molecular weight procyanidins from grape seeds enhance the impact of 5
      Fluorouracil chemotherapy on Caco-2 human colon cancer cells.
AB  - OBJECTIVE: Grape seed procyanidins (PC) are flavan-3-ol oligomers and polymers
      known for their biological activity in the gut. Grape seed extract (GSE) have
      been reported to reduce intestinal injury in a rat model of mucositis. We sought
      to investigate effects of purified PC fractions differing in mean degree of
      polymerization (mDP) combined with 5-Fluorouracil (5-FU) chemotherapy on the
      viability of colon cancer cells (Caco-2). DESIGN: SixPC fractions (F1-F6) were
      isolated from Cabernet Sauvignon seeds at two ripeness stages: pre-veraison
      unripe (immature) and ripe (mature), utilizing step gradient, low-pressure
      chromatography on a Sephadex LH-20 resin. Fractions were tested on Caco-2 cells,
      alone and in combination with 5-FU. Eluted fractions were characterized by
      phloroglucinolysis and gel permeation chromatography. Cell viability was
      determined by the 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide)
      (MTT) assay. RESULTS: All isolated fractions significantly reduced Caco-2 cell
      viability compared to the control (P<0.05), but F2 and F3 (mDP 2-6) were the most
      active fractions (immature F2 = 32% mDP 2.4, F3 = 35% mDP 5.8 and mature F2 = 13%
      mDP 3.6 and F3 = 17% mDP 5.9; percentage of viable cells remaining) on Caco-2
      cells. When combined with 5-FU, immature fractions F1-F3 enhanced the cell
      toxicity effects of 5-FU by 27-73% (P<0.05). Mature seed PC fractions (F1-F4)
      significantly enhanced the toxicity of 5-FU by 60-83% against Caco-2 cells
      (P<0.05). Moreover, some fractions alone were more potent at decreasing viability
      in Caco-2 cells (P<0.05; immature fractions = 65-68% and mature fractions = 83
      87%) compared to 5-FU alone (37%). CONCLUSIONS: PCs of mDP 2-6 (immature F1-F3
      and mature F1 and F4)not only enhanced the impact of 5-FU in killing Caco-2
      cells, but also surpassed standard 5-FU chemotherapy as an anti-cancer agent.The
      bioactivity of PC is therefore attributed primarily to lower molecular weight
      PCs.

PMID- 24905823
TI  - Oxidative stress in patients with type 1 diabetes mellitus: is it affected by a
      single bout of prolonged exercise?
AB  - Presently, no clear-cut guidelines are available to suggest the more appropriate
      physical activity for patients with type 1 diabetes mellitus due to paucity of
      experimental data obtained under patients' usual life conditions. Accordingly, we
      explored the oxidative stress levels associated with a prolonged moderate
      intensity, but fatiguing, exercise performed under usual therapy in patients with
      type 1 diabetes mellitus and matched healthy controls. Eight patients (4 men, 4
      women; 49+/-11 years; Body Mass Index 25.0+/-3.2 kg.m(-2); HbA1c 57+/-10
      mmol.mol(-1)) and 14 controls (8 men, 6 women; 47+/-11 years; Body Mass Index
      24.3+/-3.3 kg.m(-2)) performed a 3-h walk at 30% of their heart rate reserve.
      Venous blood samples were obtained before and at the end of the exercise for
      clinical chemistry analysis and antioxidant capacity. Capillary blood samples
      were taken at the start and thereafter every 30 min to determine lipid
      peroxidation. Patients showed higher oxidative stress values as compared to
      controls (95.9+/-9.7 vs. 74.1+/-12.2 mg.L(-1) H2O2; p<0.001). In both groups,
      oxidative stress remained constant throughout the exercise (p = NS), while
      oxidative defence increased significantly at the end of exercise (p<0.02) from
      1.16+/-0.13 to 1.19+/-0.10 mmol.L(-1) Trolox in patients and from 1.09+/-0.21 to
      1.22+/-0.14 mmol.L(-1) Trolox in controls, without any significant difference
      between the two groups. Oxidative stress was positively correlated to HbA1c
      (p<0.005) and negatively related with uric acid (p<0.005). In conclusion, we were
      the first to evaluate the oxidative stress in patients with type 1 diabetes
      exercising under their usual life conditions (i.e. usual therapy and diet).
      Specifically, we found that the oxidative stress was not exacerbated due to a
      single bout of prolonged moderate intensity aerobic exercise, a condition
      simulating several outdoor leisure time physical activities. Oxidative defence
      increased in both patients and controls, suggesting beneficial effects of
      prolonged aerobic fatiguing exercise.

PMID- 24905825
TI  - Upregulation of matrilin-2 expression in murine hepatic stellate cells during
      liver injury has no effect on fibrosis formation and resolution.
AB  - BACKGROUND & AIMS: Matrilins are a family of four oligomeric adaptor proteins
      whose functions in extracellular matrix assembly during pathophysiological events
      still need to be explored in more detail. Matrilin-2 is the largest family member
      and the only matrilin expressed in the naive liver. Several studies demonstrate
      that matrilin-2 interacts with collagen I, fibronectin or laminin-111-nidogen-1
      complexes. All these matrix components get upregulated during hepatic scar tissue
      formation. Therefore, we tested whether matrilin-2 has an influence on the
      formation and/or the resolution of fibrotic tissue in the mouse liver. METHODS:
      Fibrosis was induced by infection with an adenovirus encoding cytochrome P450 2D6
      (autoimmune liver damage) or by exposure to the hepatotoxin carbon tetrachloride.
      Fibrosis severity and matrilin-2 expression were assessed by
      immunohistochemistry. Hepatic stellate cells (HSCs) were isolated and analysed by
      immunocytochemistry and Transwell migration assays. RESULTS: Both autoimmune as
      well as chemically induced liver damage led to simultaneous upregulation of
      matrilin-2 and collagen I expression. Discontinuation of carbon tetrachloride
      exposure resulted in concomitant dissolution of both proteins. Activated HSCs
      were the source of de novo matrilin-2 expression. Comparing wild type and
      matrilin-2-deficient mice, no differences were detected in fibronectin and
      collagen I upregulation and resolution kinetics as well as amount or location of
      fibronectin and collagen I production and degradation. CONCLUSIONS: Our findings
      suggest that the absence of matrilin-2 has no effect on HSC activation and
      regression kinetics, synthetic activity, proliferative capacity, motility, or HSC
      apoptosis.

PMID- 24905824
TI  - Reciprocal regulation of autophagy and dNTP pools in human cancer cells.
AB  - Ribonucleotide reductase (RNR) plays a critical role in catalyzing the
      biosynthesis and maintaining the intracellular concentration of 4
      deoxyribonucleoside triphosphates (dNTPs). Unbalanced or deficient dNTP pools
      cause serious genotoxic consequences. Autophagy is the process by which
      cytoplasmic constituents are degraded in lysosomes to maintain cellular
      homeostasis and bioenergetics. However, the role of autophagy in regulating dNTP
      pools is not well understood. Herein, we reported that starvation- or rapamycin
      induced autophagy was accompanied by a decrease in RNR activity and dNTP pools in
      human cancer cells. Furthermore, downregulation of the small subunit of RNR
      (RRM2) by siRNA or treatment with the RNR inhibitor hydroxyurea substantially
      induced autophagy. Conversely, cancer cells with abundant endogenous
      intracellular dNTPs or treated with dNTP precursors were less responsive to
      autophagy induction by rapamycin, suggesting that autophagy and dNTP pool levels
      are regulated through a negative feedback loop. Lastly, treatment with si-RRM2
      caused an increase in MAP1LC3B, ATG5, BECN1, and ATG12 transcript abundance in
      xenografted Tu212 tumors in vivo. Together, our results revealed a previously
      unrecognized reciprocal regulation between dNTP pools and autophagy in cancer
      cells. 

PMID- 24905826
TI  - Highly sensitive determination of 2,4,6-trinitrotoluene and related byproducts
      using a diol functionalized column for high performance liquid chromatography.
AB  - In this work, a new detection method for complete separation of 2,4,6
      trinitrotoluene (TNT); 2,4-dinitrotoluene (2,4-DNT); 2,6-dinitrotoluene (2,6
      DNT); 2-aminodinitrotoluene (2-ADNT) and 4-aminodinitrotoluene (4-ADNT) molecules
      in high-performance liquid-chromatography (HPLC) with UV sensor has been
      developed using diol column. This approach improves on cost, time, and
      sensitivity over the existing methods, providing a simple and effective
      alternative. Total analysis time was less than 13 minutes including column re
      equilibration between runs, in which water and acetonitrile were used as gradient
      elution solvents. Under optimized conditions, the minimum resolution between 2,4
      DNT and 2,6-DNT peaks was 2.06. The recovery rates for spiked environmental
      samples were between 95-98%. The detection limits for diol column ranged from
      0.78 to 1.17 ug/L for TNT and its byproducts. While the solvent consumption was
      26.4 mL/min for two-phase EPA and 30 mL/min for EPA 8330 methods, it was only 8.8
      mL/min for diol column. The resolution was improved up to 49% respect to two
      phase EPA and EPA 8330 methods. When compared to C-18 and phenyl-3 columns,
      solvent usage was reduced up to 64% using diol column and resolution was enhanced
      approximately two-fold. The sensitivity of diol column was afforded by the
      hydroxyl groups on polyol layer, joining the formation of charge-transfer
      complexes with nitroaromatic compounds according to acceptor-donor interactions.
      Having compliance with current requirements, the proposed method demonstrates
      sensitive and robust separation. 

PMID- 24905827
TI  - BETting on a new prostate cancer treatment.

PMID- 24905829
TI  - Formulation and evaluation of lipid based taste masked granules of ondansetron
      HCl.
AB  - INTRODUCTION AND AIM: Various taste masking approaches comprising the excipients
      which delay the reach of the drug to taste buds are reported. Lipidic substances
      can act as release retarding agent and provides a matrix base responsible for
      suppressing the bitter taste of drug. This work was aimed to study the influence
      of different proportions of a lipid carrier on the inhibition of bitterness of
      the drug vis-a-vis in vitro release of drug from the granules. METHODS: The lipid
      matrix granules of ondansetron HCl with Geleol pellets (glycerol monostearate)
      were obtained by manual hot melt fusion technique. The prepared granules were
      characterized by SEM, DSC and XRD. The taste assessment of prepared granules was
      done by in vitro method based on drug release. RESULTS: Distribution of drug
      inside the lipid-matrix granules was not properly analyzed by DSC and XRD,
      moreover these studies revealed no interaction between the drug and lipid. The
      dissolution tests displayed the significant retardation of drug release from the
      granules compared to pure drug and additionally indicated the attainment of
      matrix system via appearance of unbroken granules during in vitro testing.
      Higuchi relationship for drug release was obtained by drug release kinetics,
      which also revealed the functioning drug release mechanism, as diffusion
      controlled but the addition of hydrophilic substance (Cab-o-sil) has changed the
      mechanism of drug release. CONCLUSION: The proportions of Geleol and Cab-o-sil
      taken in granules had affected the dissolution profile. Higher amount of GE
      resulted in high taste masking ability.

PMID- 24905828
TI  - Grouper tshbeta promoter-driven transgenic zebrafish marks proximal kidney tubule
      development.
AB  - Kidney tubule plays a critical role in recovering or secreting solutes, but the
      detailed morphogenesis remains unclear. Our previous studies have found that
      grouper tshbeta (gtshbeta) is also expressed in kidney, however, the distribution
      significance is still unknown. To understand the gtshbeta role and kidney tubule
      morphogenesis, here, we have generated a transgenic zebrafish line
      Tg(gtshbeta:GFP) with green fluorescent protein driven by the gtshbeta promoter.
      Similar to the endogenous tshbeta in zebrafish or in grouper, the gtshbeta
      promoter-driven GFP is expressed in pituitary and kidney, and the developing
      details of proximal kidney tubule are marked in the transgenic zebrafish line.
      The gfp initially transcribes at 16 hours post fertilization (hpf) above the
      dorsal mesentery, and partially co-localizes with pronephric tubular markers
      slc20a1a and cdh17. Significantly, the GFP specifically localizes in proximal
      pronephric segments during embryogenesis and resides at kidney duct epithelium in
      adult fish. To test whether the gtshbeta promoter-driven GFP may serve as a
      readout signal of the tubular development, we have treated the embryos with
      retinoic acid signaing (RA) reagents, in which exogenous RA addition results in a
      distal extension of the proximal segments, while RA inhibition induces a weakness
      and shortness of the proximal segments. Therefore, this transgenic line provides
      a useful tool for genetic or chemical analysis of kidney tubule. 

PMID- 24905830
TI  - Proniosome-derived niosomes for tacrolimus topical ocular delivery: in vitro
      cornea permeation, ocular irritation, and in vivo anti-allograft rejection.
AB  - The objective of this study was to develop proniosome-derived niosomes for
      topical ophthalmic delivery of Tacrolimus (FK506). The FK506 loaded proniosomes
      containing poloxamer 188 and lecithin as surfactants, cholesterol as a
      stabilizer, and minimal amount of ethanol and trace water reconstituted to
      niosomes prior to use. The stability of FK506 loaded proniosomes was assessed,
      and the morphology, size, zeta potential, surface tension, and entrapment
      efficiency of the derived niosomes were characterized, indicating they were
      feasible for instillation in the eyes. The in vitro permeation of FK506 through
      the freshly excised rabbit cornea, the cumulative permeation amount of FK506 from
      niosomes, and the drug retention in the cornea all exhibited significant increase
      as compared to 0.1% FK506 commercial ointments. The in vivo ocular irritation
      test of 0.1% FK506 loaded niosomes instilled 4 times per day in rat eyes for 21
      consecutive days showed no irritation and good biocompatibility with cornea. The
      in vivo anti-allograft rejection assessment was performed in a Sprague-Dawley
      (SD) rat corneal xenotransplantation model. The results showed treatment with
      0.1% FK506 loaded niosomes delayed the occurrence of corneal allograft rejection
      and significantly prolonged the median survival time of corneal allografts
      to13.86+/-0.80days as compared with those treated with 1% Cyclosporine (CsA) eye
      drops, drug-free niosomes, or untreated. In conclusion, the proniosome-derived
      niosomes may be a promising vehicle for effective ocular drug delivery of FK506. 

PMID- 24905831
TI  - Epidemic process over the commute network in a metropolitan area.
AB  - An understanding of epidemiological dynamics is important for prevention and
      control of epidemic outbreaks. However, previous studies tend to focus only on
      specific areas, indicating that application to another area or intervention
      strategy requires a similar time-consuming simulation. Here, we study the
      epidemic dynamics of the disease-spread over a commute network, using the Tokyo
      metropolitan area as an example, in an attempt to elucidate the general
      properties of epidemic spread over a commute network that could be used for a
      prediction in any metropolitan area. The model is formulated on the basis of a
      metapopulation network in which local populations are interconnected by actual
      commuter flows in the Tokyo metropolitan area and the spread of infection is
      simulated by an individual-based model. We find that the probability of a global
      epidemic as well as the final epidemic sizes in both global and local
      populations, the timing of the epidemic peak, and the time at which the epidemic
      reaches a local population are mainly determined by the joint distribution of the
      local population sizes connected by the commuter flows, but are insensitive to
      geographical or topological structure of the network. Moreover, there is a strong
      relation between the population size and the time that the epidemic reaches this
      local population and we are able to determine the reason for this relation as
      well as its dependence on the commute network structure and epidemic parameters.
      This study shows that the model based on the connection between the population
      size classes is sufficient to predict both global and local epidemic dynamics in
      metropolitan area. Moreover, the clear relation of the time taken by the epidemic
      to reach each local population can be used as a novel measure for intervention;
      this enables efficient intervention strategies in each local population prior to
      the actual arrival. 

PMID- 24905832
TI  - A gestational profile of placental exosomes in maternal plasma and their effects
      on endothelial cell migration.
AB  - Studies completed to date provide persuasive evidence that placental cell-derived
      exosomes play a significant role in intercellular communication pathways that
      potentially contribute to placentation and development of materno-fetal vascular
      circulation. The aim of this study was to establish the gestational-age release
      profile and bioactivity of placental cell-derived exosome in maternal plasma.
      Plasma samples (n = 20 per pregnant group) were obtained from non-pregnant and
      pregnant women in the first (FT, 6-12 weeks), second (ST, 22-24 weeks) and third
      (TT, 32-38 weeks) trimester. The number of exosomes and placental exosome
      contribution were determined by quantifying immunoreactive exosomal CD63 and
      placenta-specific marker (PLAP), respectively. The effect of exosomes isolated
      from FT, ST and TT on endothelial cell migration were established using a real
      time, live-cell imaging system (Incucyte). Exosome plasma concentration was more
      than 50-fold greater in pregnant women than in non-pregnant women (p<0.001).
      During normal healthy pregnancy, the number of exosomes present in maternal
      plasma increased significantly with gestational age by more that two-fold
      (p<0.001). Exosomes isolated from FT, ST and TT increased endothelial cell
      migration by 1.9+/-0.1, 1.6+/-0.2 and 1.3+/-0.1-fold, respectively compared to
      the control. Pregnancy is associated with a dramatic increase in the number of
      exosomes present in plasma and maternal plasma exosomes are bioactive. While the
      role of placental cell-derived exosome in regulating maternal and/or fetal
      vascular responses remains to be elucidated, changes in exosome profile may be of
      clinical utility in the diagnosis of placental dysfunction. 

PMID- 24905835
TI  - Economic analysis of greenhouse lighting: light emitting diodes vs. high
      intensity discharge fixtures.
AB  - Lighting technologies for plant growth are improving rapidly, providing numerous
      options for supplemental lighting in greenhouses. Here we report the
      photosynthetic (400-700 nm) photon efficiency and photon distribution pattern of
      two double-ended HPS fixtures, five mogul-base HPS fixtures, ten LED fixtures,
      three ceramic metal halide fixtures, and two fluorescent fixtures. The two most
      efficient LED and the two most efficient double-ended HPS fixtures had nearly
      identical efficiencies at 1.66 to 1.70 micromoles per joule. These four fixtures
      represent a dramatic improvement over the 1.02 micromoles per joule efficiency of
      the mogul-base HPS fixtures that are in common use. The best ceramic metal halide
      and fluorescent fixtures had efficiencies of 1.46 and 0.95 micromoles per joule,
      respectively. We also calculated the initial capital cost of fixtures per photon
      delivered and determined that LED fixtures cost five to ten times more than HPS
      fixtures. The five-year electric plus fixture cost per mole of photons is thus
      2.3 times higher for LED fixtures, due to high capital costs. Compared to
      electric costs, our analysis indicates that the long-term maintenance costs are
      small for both technologies. If widely spaced benches are a necessary part of a
      production system, the unique ability of LED fixtures to efficiently focus
      photons on specific areas can be used to improve the photon capture by plant
      canopies. Our analysis demonstrates, however, that the cost per photon delivered
      is higher in these systems, regardless of fixture category. The lowest lighting
      system costs are realized when an efficient fixture is coupled with effective
      canopy photon capture. 

PMID- 24905834
TI  - Genomics of post-prandial lipidomic phenotypes in the Genetics of Lipid lowering
      Drugs and Diet Network (GOLDN) study.
AB  - BACKGROUND: Increased postprandial lipid (PPL) response to dietary fat intake is
      a heritable risk factor for cardiovascular disease (CVD). Variability in
      postprandial lipids results from the complex interplay of dietary and genetic
      factors. We hypothesized that detailed lipid profiles (eg, sterols and fatty
      acids) may help elucidate specific genetic and dietary pathways contributing to
      the PPL response. METHODS AND RESULTS: We used gas chromatography mass
      spectrometry to quantify the change in plasma concentration of 35 fatty acids and
      11 sterols between fasting and 3.5 hours after the consumption of a high-fat meal
      (PPL challenge) among 40 participants from the GOLDN study. Correlations between
      sterols, fatty acids and clinical measures were calculated. Mixed linear
      regression was used to evaluate associations between lipidomic profiles and
      genomic markers including single nucleotide polymorphisms (SNPs) and methylation
      markers derived from the Affymetrix 6.0 array and the Illumina Methyl450 array,
      respectively. After the PPL challenge, fatty acids increased as well as sterols
      associated with cholesterol absorption, while sterols associated with cholesterol
      synthesis decreased. PPL saturated fatty acids strongly correlated with
      triglycerides, very low-density lipoprotein, and chylomicrons. Two SNPs
      (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1)
      gene were associated with b-Sitosterol after correction for multiple testing
      (P<=4.5*10(-10)). SORBS1 has been linked to obesity and insulin signaling. No
      other markers reached the genome-wide significance threshold, yet several other
      biologically relevant loci are highlighted (eg, PRIC285, a co-activator of
      PPARa). CONCLUSIONS: Integration of lipidomic and genomic data has the potential
      to identify new biomarkers of CVD risk.

PMID- 24905836
TI  - Nonparametric Prediction of Event Times for Analysis of Failure-Time Data.
AB  - In trials with failure-time outcomes, statistical information is determined by
      accumulated events. Interim and final analyses are performed after a prespecified
      number of events have been observed. It is of interest to predict when a
      prespecified number of events will be observed based on accumulating data. We
      propose a fully Bayesian nonparametric approach in modeling the survival
      probabilities. We compare the accuracy and precision of this approach to proposed
      parametric and semi-parametric methods. In summary, the proposed method offers
      greater flexibility and based on our studies has the ability to match or
      outperform existing methods. 

PMID- 24905837
TI  - Temperature management in neurological and neurosurgical intensive care units.

PMID- 24905838
TI  - Intraoperative temperature management.

PMID- 24905839
TI  - Editorial: do skull fractures matter?

PMID- 24905840
TI  - Pediatric skull fractures: the need for surgical intervention, characteristics,
      complications, and outcomes.
AB  - OBJECT: Head trauma is a common cause of morbidity and mortality in the pediatric
      population and often results in a skull fracture. Pediatric skull fractures are
      distinct from adult fractures. Pediatric fractures have a greater capacity to
      remodel, but the pediatric brain and craniofacial skeleton are still developing.
      Although pediatric head trauma has been extensively studied, there is sparse
      literature regarding skull fractures. The authors' aim was to investigate the
      characteristics, injuries, complications, and outcomes of the patients in whom
      surgical intervention was needed for skull fractures. METHODS: The authors
      performed a retrospective review of patients presenting to the emergency
      department of a pediatric Level I trauma center between 2000 and 2005 with skull
      fractures. Patient demographics, mechanism of injury, associated injuries,
      fracture bone involvement, surgical intervention, complications, and outcomes
      were analyzed. Groups treated nonoperatively, for skull fracture repair, and for
      traumatic brain injury were compared. RESULTS: A total of 897 patients with a
      skull fracture were analyzed. Most patients (n = 772, 86.1%) were treated
      nonoperatively (Non-Op group). Fifty-eight patients (6.5%) underwent repair of
      the fracture (Repair group) and 67 (7.5%) required intervention for treatment of
      traumatic brain injury (TBI group). The Non-Op group was significantly younger,
      and the TBI group had a lower initial Glasgow Coma Scale (GCS) score. A fall
      (51.2%) was the most common mechanism of injury in the Non-Op group, whereas a
      motor vehicle crash (23.9%) and being hit in the head with an object (48.2%) were
      most prevalent in the TBI and Repair groups, respectively. Associated injuries
      were seen in all 3 groups, with brain injury (hematoma) being the most common.
      Frontal bone fracture was seen most in the Repair and TBI groups, and the
      parietal bone was the most frequent bone fractured in the Non-Op group. Patients
      in the TBI group were much more likely to have 2 or 3 skull bones fractured. In
      the Repair group, 36.2% had a complication (38.0% intervention related and 62.0%
      trauma related), but no patient had a worsening of their neurological status. In
      the TBI group, 48.7% of the patients suffered a complication, the vast majority
      (90.6%) of which were related to the trauma. CONCLUSIONS: The majority of
      pediatric skull fractures can be managed conservatively. Of those requiring
      surgical intervention, fewer than half of the surgeries are performed solely for
      skull fracture repair only. Patients hit in the head with an object or involved
      in a motor vehicle crash are more likely to need surgical intervention either to
      repair the skull fracture or for TBI management, respectively. Frontal bone
      fractures are more likely to necessitate repair, and those patients treated for
      TBI have a greater incidence of 2 or 3 bones involved in the fracture.
      Complications occurred but most were related to underlying trauma, not the
      surgery. No patients who underwent intervention for repair of their skull
      fracture only had a worsening of their neurological status.

PMID- 24905842
TI  - Intracranial infantile hemangiopericytoma.
AB  - Intracranial infantile hemangiopericytomas (HPCs) are exceedingly rare lesions.
      Only 11 cases have been previously reported in the literature. As such, little is
      known about the etiology, long-term prognosis, and optimal treatment paradigm.
      Clinically, they are consistently less aggressive than those in adults. The
      authors present the case of a 2-month-old boy with an intracranial HPC, review
      the available literature, discuss the evolving concepts of what defines an HPC,
      and offer a potential explanation to how HPC histology might relate to the
      clinical behavior of these lesions. 

PMID- 24905841
TI  - Differences in vascular endothelial growth factor receptor expression and
      correlation with the degree of enhancement in medulloblastoma.
AB  - OBJECT: Vascular endothelial growth factor (VEGF) is the major proangiogenic
      factor in many solid tumors. Vascular endothelial growth factor receptor (VEGFR)
      is expressed in abundance in pediatric patients with medulloblastoma and is
      associated with tumor metastasis, poor prognosis, and proliferation. Gadolinium
      enhancement on MRI has been suggested to have prognostic significance for some
      tumors. The association of VEGF/VEGFR and Gd enhancement in medulloblastoma has
      never been closely examined. The authors therefore sought to evaluate whether Gd
      enhancing medulloblastomas have higher levels of VEGFR and CD31. Outcomes and
      survival in patients with enhancing and nonenhancing tumors were also compared.
      METHODS: A retrospective analysis of patients with enhancing, nonenhancing, and
      partially enhancing medulloblastomas was performed. Primary end points included
      risk stratification, extent of resection, and perioperative complications. A
      cohort of 3 enhancing and 3 nonenhancing tumors was selected for VEGFR and CD31
      analysis as well as microvessel density measurements. RESULTS: Fifty-eight
      patients were analyzed, and 20.7% of the medulloblastomas in these patients were
      nonenhancing. Enhancing medulloblastomas exhibited strong VEGFR1/2 and CD31
      expression relative to nonenhancing tumors. There was no significant difference
      in perioperative complications or patient survival between the 2 groups.
      CONCLUSIONS: These results suggest that in patients with medulloblastoma the
      presence of enhancement on MRI may correlate with increased vascularity and
      angiogenesis, but does not correlate with worse patient prognosis in the short or
      long term.

PMID- 24905843
TI  - Experimental use of photodynamic therapy in high grade gliomas: a review focused
      on 5-aminolevulinic acid.
AB  - Photodynamic therapy (PDT) consists of a laser light exposure of tumor cells
      photosensitized by general or local administration of a pharmacological agent.
      Nowadays, PDT is a clinically established modality for treatment of many cancers.
      5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven its
      rational in fluoro-guided resection of malignant gliomas due to a selective tumor
      uptake and minimal skin sensitization. Moreover, the relatively specific
      accumulation of photosensitizing PPIX within the tumor cells has gained interest
      in the PDT of malignant gliomas. Several experimental and clinical studies have
      then established ALA-PDT as a valuable adjuvant therapy in the management of
      malignant gliomas. However, the procedure still requires optimizations in the
      fields of tissue oxygenation status, photosensitizer concentration or scheme of
      laser light illumination. In this extensive review, we focused on the methods and
      results of ALA-PDT for treating malignant gliomas in experimental conditions. The
      biological mechanisms, the effects on tumor and normal brain tissue, and finally
      the critical issues to optimize the efficacy of ALA-PDT were discussed. 

PMID- 24905844
TI  - How much does mental health discrimination cost: valuing experienced
      discrimination in relation to healthcare care costs and community participation.
AB  - AIMS: This study builds on existing research on the prevalence and consequences
      of mental illness discrimination by investigating and quantifying the
      relationships between experienced discrimination and costs of healthcare and
      leisure activities/social participation among secondary mental health service
      users in England. METHODS: We use data from the Mental Illness-Related
      Investigations on Discrimination (MIRIAD) study (n = 202) and a subsample of the
      Viewpoint study (n = 190). We examine experiences of discrimination due to mental
      illness in the domains of personal relationships, community activities, and
      health care, and how such experienced discrimination relates to patterns of
      service use and engagement in leisure activities. RESULTS: Our findings show that
      the cost of health services used for individuals who reported previous
      experiences of discrimination in a healthcare setting was almost twice as high as
      for those who did not report any discrimination during the last 12 months
      (Relative Risk: 1.73; 95% Confidence Interval (CI): 1.39, 2.17) and this was
      maintained after controlling for symptoms and functioning. Experienced
      discrimination in healthcare (Relative Risk: 0.83; 95% CI: 0.81, 0.84) or in
      relationships (Relative Risk: 0.89; 95% CI: 0.87, 0.91), however, was associated
      with lower participation in, and hence lower costs of, leisure activities.
      Individuals who reported any discrimination in a healthcare setting had, on
      average, L434 higher costs associated with health service use while reported
      discrimination in the community was associated with increased leisure costs of
      L32. CONCLUSIONS: These findings make an important initial step towards
      understanding the magnitude of the costs of mental health-related discrimination.

PMID- 24905845
TI  - Heme-heme oxygenase 1 system is involved in ammonium tolerance by regulating
      antioxidant defence in Oryza sativa.
AB  - Despite substantial evidence showing the ammonium-altered redox homeostasis in
      plants, the involvement and molecular mechanism of heme-heme oxygenase 1 (heme
      HO1), a novel antioxidant system, in the regulation of ammonium tolerance remain
      elusive. To fill in these gaps, the biological function of rice HO1 (OsSE5) was
      investigated. Results showed that NH4 Cl up-regulated rice OsSE5 expression.
      Oxidative stress and subsequent growth inhibition induced by excess NH4 Cl was
      partly mitigated by pretreatment with carbon monoxide (CO, a by-product of HO1
      activity) or intensified by zinc protoporphyrin (ZnPP, a potent inhibitor of HO1
      activity). Pretreatment with HO1 inducer hemin, not only up-regulated OsSE5
      expression and HO activity, but also rescued the down-regulation of antioxidant
      transcripts, total and related isozymatic activities, thus significantly
      counteracting the excess NH4 Cl-triggered reactive oxygen species overproduction,
      lipid peroxidation and growth inhibition. OsSE5 RNAi transgenic rice plants
      revealed NH4 Cl-hypersensitive phenotype with impaired antioxidant defence, both
      of which could be rescued by CO but not hemin. Transgenic Arabidopsis plants over
      expressing OsSE5 also exhibited enhanced tolerance to NH4 Cl, which might be
      attributed to the up-regulation of several antioxidant transcripts. Altogether,
      these results illustrated the involvement of heme-HO1 system in ammonium
      tolerance by enhancing antioxidant defence, which may improve plant tolerance to
      excess ammonium fertilizer. 

PMID- 24905846
TI  - Artificial warming facilitates growth but not survival of plateau frog (Rana
      kukunoris) tadpoles in presence of gape-limited predatory beetles.
AB  - BACKGROUND: Global warming has been frequently demonstrated to increase growth
      rate in larval amphibians that have considerable phenotypic plasticity; this may
      lead to an increase in larval survival because large larvae are less likely to be
      captured by gape-limited predators. This study is to test whether warming could
      improve tadpole growth and thereby enhance the tadpole survival in plateau frog
      Rana kukunoris. METHODOLOGY: We conducted an experiment involving growing
      tadpoles under two contrasting temperatures, i.e. ambient temperature vs. warming
      by 3.8 degrees C, with and without their major predators--the gape-limited
      predaceous diving beetles Agabus sp. in eastern Tibetan Plateau, in a factorial
      arrangement. We recorded the survival and measured body fresh weight and
      morphological characteristics of the tadpoles. PRINCIPAL FINDINGS: Warming
      significantly increased body fresh weight in the presence of predators after
      three weeks of treatments. However, the predators imposed significant and similar
      effects on the survival of tadpoles under both ambient and elevated temperatures,
      with the effects mostly occurring in the first three weeks of the experiment.
      Changes in the body form, i.e. the greater whole length at a given fresh weight
      and the longer tail at a given body length, could have acted as mechanisms of
      defense and escape for the tadpoles. CONCLUSIONS/SIGNIFICANCE: Warming did not
      increase tadpole survival with or without presence of predators. Moreover, an
      increased growth rate (due to warming in the presence of predators) was not a
      major factor contributing to the tadpole survival. We postulate that even if
      warming increases the tadpole growth rate in the plateau frog, it does not
      necessarily improve their survival in the presence of gape-limited predators.

PMID- 24905847
TI  - Screening of diabetes of youth for hepatocyte nuclear factor 1 mutations:
      clinical phenotype of HNF1beta-related maturity-onset diabetes of the young and
      HNF1alpha-related maturity-onset diabetes of the young in Japanese.
AB  - AIM: To compare the prevalence and clinical features of HNF1beta-related MODY and
      HNF1alpha-related MODY in Japanese. METHODS: We enrolled 230 Japanese patients
      with suspected MODY and examined them for HNF1alpha and HNF1beta mutations. We
      characterized the clinical features of HNF1beta-related MODY (HNF1beta-MODY) and
      HNF1alpha-related MODY (HNF1alpha-MODY). RESULTS: Six patients had HNF1beta
      mutations, four of which were large gene deletions and 24 patients had HNF1alpha
      mutations, which included one gene deletion. The mean fasting plasma glucose
      level at onset of HNF1beta-MODY was considerably higher and the age of onset of
      HNF1beta-MODY was considerably older than they were for HNF1alpha-MODY, while the
      mean BMI and C-peptide index at onset were similar. Three patients with HNF1beta
      MODY were found to have dorsal pancreatic agenesis and four of them had whole
      gene deletion. Five of the patients with HNF1beta-MODY had insulin secretion
      defects and were treated with insulin, and four of these did not have a parent
      with overt diabetes. CONCLUSION: HNF1beta-MODY may present as beta-cell
      dysfunction in Japanese rather than as hyperinsulinaemia, which it does among
      European/American. This dysfunction might result from an intrinsically lower
      capacity for insulin secretion in Japanese. HNF1beta-MODY has an older age of
      onset than HNF1alpha-MODY, which may suggest lower penetrance of the disease. In
      addition, HNF1beta-MODY has a broad spectrum of clinical manifestations, some of
      which are detectable by imaging. This may be helpful in some cases for selecting
      HNF1beta-MODY candidates for genetic testing.

PMID- 24905848
TI  - Effect of CTGF/CCN2 on osteo/cementoblastic and fibroblastic differentiation of a
      human periodontal ligament stem/progenitor cell line.
AB  - Appropriate mechanical loading during occlusion and mastication play an important
      role in maintaining the homeostasis of periodontal ligament (PDL) tissue.
      Connective tissue growth factor (CTGF/CCN2), a matricellular protein, is known to
      upregulate extracellular matrix production, including collagen in PDL tissue.
      However, the underlying mechanisms of CTGF/CCN2 in regulation of PDL tissue
      integrity remain unclear. In this study, we investigated the effect of CTGF/CCN2
      on osteo/cementoblastic and fibroblastic differentiation of human PDL stem cells
      using the cell line 1-11. CTGF/CCN2 expression in rat PDL tissue and human PDL
      cells (HPDLCs) was confirmed immunohisto/cytochemically. Mechanical loading was
      found to increase gene expression and secretion of CTGF/CCN2 in HPDLCs. CTGF/CCN2
      upregulated the proliferation and migration of 1-11 cells. Furthermore, increased
      bone/cementum-related gene expression in this cell line led to mineralization. In
      addition, combined treatment of 1-11 cells with CTGF/CCN2 and transforming growth
      factor-beta1 (TGF-beta1) significantly promoted type I collagen and fibronectin
      expression compared with that of TGF-beta1 treatment alone. Thus, these data
      suggest the underlying biphasic effects of CTGF/CCN2 in 1-11 cells, inducible
      osteo/cementoblastic, and fibroblastic differentiation dependent on the
      environmental condition. CTGF/CCN2 may contribute to preservation of the
      structural integrity of PDL tissue, implying its potential use as a therapeutic
      agent for PDL regeneration.

PMID- 24905849
TI  - Polybrominated diphenyl ether accumulation in an agricultural soil ecosystem
      receiving wastewater sludge amendments.
AB  - Few studies have addressed bioaccumulation of organic pollutants associated with
      land-application of biosolids. We thus examined PBDE burdens within a soil
      ecosystem receiving long-term sludge amendments and a reference soil ecosystem
      receiving only manure inputs. No PBDEs were detected in reference site samples,
      but sludge-amended soils contained 17 600 +/- 2330 MUg/kg ?3-7PBDE (total organic
      carbon (TOC) basis). ?3-7PBDE burdens were highest in soil invertebrates with the
      greatest contact with sludge-amended soil (e.g., ?3-7PBDE of 10 300 +/- 2670 and
      3000 +/- 200 MUg/kg lipid for earthworms and detritivorous woodlice,
      respectively). PBDEs were below quantitation limits in vegetation from the sludge
      amended site. Surprisingly, we measured quantifiable PBDE burdens in only a
      single sample of predaceous ground spiders from the sludge-amended site. BDE-209
      burdens in sludge-amended soil and earthworms were 7500 +/- 2800 MUg/kg TOC and
      6500 +/- 4100 MUg/kg lipid, respectively. BDE 209 was detected in fewer taxa, but
      the burden in a detritivorous millipede composite was high (86 000 MUg/kg lipid).
      PBDE congener patterns differed among species, with worms and ground beetles
      exhibiting Penta-BDE-like patterns. Penta-BDE biota-soil accumulation factors
      (BSAFs) ranged from 0.006 to 1.2, while BDE-209 BSAFs ranged from 0.07 to 10.5.
      delta(13)C and delta(15)N isotope signatures were poorly correlated with PBDE
      burdens, but sludge-amended samples were significantly delta(15)N enriched. 

PMID- 24905850
TI  - Macrophages: central regulators of iron balance.
AB  - Macrophages are important to immune function and also actively participate in
      iron homeostasis. The involvement of splenic and liver macrophages in the
      processing of effete erythrocytes and the subsequent return of iron to the
      circulation is well established, and the molecular details of iron recycling have
      been characterized recently. Another important aspect regarding iron handling by
      macrophages is their capacity to act as immune cells, which involves the
      inflammatory response, as well as other pathological conditions in which
      macrophages are central. This review discusses the latest advances in macrophage
      iron trafficking and the pathophysiological consequences of altered iron
      homeostasis in these cells. 

PMID- 24905851
TI  - LiFe(MoO4)2 as a novel anode material for lithium-ion batteries.
AB  - Polycrystalline LiFe(MoO4)2 is successfully synthesized by solid-state reaction
      and examined as anode material for lithium-ion batteries in terms of
      galvanostatic charge-discharge cycling, cyclic voltammograms (CV), galvanostatic
      intermittent titration technique (GITT), and electrochemical impedance
      spectroscopy (EIS). The LiFe(MoO4)2 electrode delivers a high capacity of 1034
      mAh g(-1) at a current density of 56 mA g(-1) between 3 and 0.01 V, indicating
      that nearly 15 Li(+) ions are involved in the electrochemical cycling.
      LiFe(MoO4)2 also exhibits a stable capacity of 580 mAh g(-1) after experiencing
      irreversible capacity loss in the first several cycles. Moreover, the Li-ion
      storage mechanism for LiFe(MoO4)2 is suggested on the basis of the ex situ X-ray
      diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) at
      different insertion/extraction depths. A successive structural transition from
      triclinic structure to cubic structure is observed, and the tetrahedral
      coordination of Mo by oxygen in LiFe(MoO4)2 changes to octahedral coordination in
      Li2MoO3, correspondingly. When being discharged to 0.01 V, the active electrode
      is likely to be composed of Fe and Mo metal particles and amorphous Li2O due to
      the multielectron conversion reaction. The insights obtained from this study will
      benefit the design of new anode materials for lithium-ion batteries. 

PMID- 24905852
TI  - Infantile haemangiomas that failed treatment with propranolol: clinical and
      histopathological features.
AB  - AIM: To describe the clinical and histopathological characteristics of infantile
      haemangiomas that failed treatment with oral propranolol . DESIGN: This study is
      a case series from the vascular birthmarks clinic at Royal Children's Hospital,
      Melbourne. PATIENTS: The patients for this study were infants who commenced
      treatment with oral propranolol before 6 months of age and who were treated for
      at least 4 months without a satisfactory result. For histology and
      immunohistochemistry, tissue from the four non-responding patients who
      subsequently underwent surgical excision was matched with four historical
      controls. OUTCOME MEASURES: Based on medical record review and photographic
      assessments, infants were defined as having failed treatment with oral
      propranolol if the infantile haemangioma either continued to grow or showed 20%
      improvement or less. Tissue sections were examined for tissue structure, mast
      cells, sympathetic innervations and beta-2 adrenergic receptor expression, and
      the number of mast cells and beta-2 adrenergic positive cells. RESULTS: From a
      group of 135 infants who met the inclusion criteria, 14 infants failed
      propranolol treatment. Eleven of these infants had focal facial haemangiomas. No
      difference was seen in tissue morphology, tissue innervations, beta-2 adrenergic
      receptor expression, cell number or mast cell distribution, and number between
      non-responding and control haemangiomas. CONCLUSION: We report a treatment
      failure rate of 10%, which is higher than previously reported. Focal facial
      lesions failed to respond twice as frequently as other types of haemangioma. No
      histopathological reason was identified to indicate why some haemangiomas failed
      to respond.

PMID- 24905853
TI  - Monitoring and detection platform to prevent anomalous situations in home care.
AB  - Monitoring and tracking people at home usually requires high cost hardware
      installations, which implies they are not affordable in many situations. This
      study/paper proposes a monitoring and tracking system for people with medical
      problems. A virtual organization of agents based on the PANGEA platform, which
      allows the easy integration of different devices, was created for this study. In
      this case, a virtual organization was implemented to track and monitor patients
      carrying a Holter monitor. The system includes the hardware and software required
      to perform: ECG measurements, monitoring through accelerometers and WiFi
      networks. Furthermore, the use of interactive television can moderate
      interactivity with the user. The system makes it possible to merge the
      information and facilitates patient tracking efficiently with low cost. 

PMID- 24905854
TI  - "SmartMonitor"--an intelligent security system for the protection of individuals
      and small properties with the possibility of home automation.
AB  - "SmartMonitor" is an intelligent security system based on image analysis that
      combines the advantages of alarm, video surveillance and home automation systems.
      The system is a complete solution that automatically reacts to every learned
      situation in a pre-specified way and has various applications, e.g., home and
      surrounding protection against unauthorized intrusion, crime detection or
      supervision over ill persons. The software is based on well-known and proven
      methods and algorithms for visual content analysis (VCA) that were appropriately
      modified and adopted to fit specific needs and create a video processing model
      which consists of foreground region detection and localization, candidate object
      extraction, object classification and tracking. In this paper, the "SmartMonitor"
      system is presented along with its architecture, employed methods and algorithms,
      and object analysis approach. Some experimental results on system operation are
      also provided. In the paper, focus is put on one of the aforementioned
      functionalities of the system, namely supervision over ill persons. 

PMID- 24905855
TI  - Kondo effect of cobalt adatoms on a graphene monolayer controlled by substrate
      induced ripples.
AB  - The Kondo effect, a widely studied phenomenon in which the scattering of
      conduction electrons by magnetic impurities increases as the temperature T is
      lowered, depends strongly on the density of states at the Fermi energy. It has
      been predicted by theory that magnetic impurities on free-standing monolayer
      graphene exhibit the Kondo effect and that control of the density of states at
      the Fermi level by external means can be used to switch the effect on and off.
      However, though transport data for Co adatoms on graphene monolayers on several
      substrates have been reported, there exists no evidence for a Kondo effect. Here
      we probe the role of the substrate on the Kondo effect of Co on graphene by
      combining low-temperature scanning tunneling microscopy and spectroscopy
      measurements with density functional theory calculations. We use a Ru(0001)
      substrate that is known to cause graphene to ripple, yielding a moire
      superlattice. The experimental data show a sharp Kondo resonance peak near the
      Fermi energy from only Co adatoms at the edge of atop regions of the moire
      pattern. The theoretical results show that the variation of the distance from the
      graphene to the Ru substrate, which controls the spin polarization and local
      density of states at the Fermi energy, is the key factor for the appearance of
      the Kondo resonance. The results suggest that rippling of graphene by suitable
      substrates is an additional lever for tuning and selectively switching the
      appearance of the Kondo effect. 

PMID- 24905856
TI  - Assembly of highly standardized gene fragments for high-level production of
      porphyrins in E. coli.
AB  - Standardization of molecular cloning greatly facilitates advanced DNA
      engineering, parts sharing, and collaborative efforts such as the iGEM
      competition. All of these attributes facilitate exploitation of the wealth of
      genetic information made available by genome and RNA sequencing. Standardization
      also comes at the cost of reduced flexibility. We addressed this paradox by
      formulating a set of design principles aimed at maximizing standardization while
      maintaining high flexibility in choice of cloning technique and minimizing the
      impact of standard sequences. The design principles were applied to formulate a
      molecular cloning pipeline and iteratively assemble and optimize a six-gene
      pathway for protoporphyrin IX synthesis in Escherichia coli. State of the art
      production levels were achieved through two simple cycles of engineering and
      screening. The principles defined here are generally applicable and simplifies
      the experimental design of projects aimed at biosynthetic pathway construction or
      engineering.

PMID- 24905857
TI  - New drugs 2014, part 2.

PMID- 24905858
TI  - Tropisetron attenuates cisplatin-induced nephrotoxicity in mice.
AB  - Nephrotoxicity is one of the most important complications of cisplatin, a potent
      chemotherapeutic agent used in the treatment of various malignancies. 5-HT3
      antagonists are widely used to counteract chemotherapy-induced emesis and new
      studies reveal that they poses notable anti-inflammatory properties. In current
      study, we investigated the effects of 5-HT3 antagonists on cisplatin induced
      nephrotoxicity in mice. To identify the underlying mechanism of renal protection
      by tropisetron, we investigated the probable involvement of alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR). A single injection of cisplatin (20mg/kg;
      i.p) induced nephrotoxicity, 5-HT3 antagonists (tropisetron, granisetron and
      ondansetron,) were given twice daily for 3 day (3mg/kg; i.p). Finally animals
      were euthanized and blood sample was collected to measure urea and creatinin
      level. Also kidneys were removed for histopathological examination and
      biochemical measurements including glutathione (GSH), malondialdehyde (MDA),
      superoxide dismutase (SOD) activity, inducible nitric oxide synthase (iNOS)
      expression and inflammatory cytokines. Tropisetron decreased the expression of
      inflammatory molecules including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1beta) and iNOS and improved histopathological damage and
      renal dysfunction. However other 5-HT3 antagonists, granisetron or ondansetron do
      not have any elicit effects on biochemical markers and histological damages.
      Since methyllycaconitine, antagonist of alpha7nAChR, was unable to reverse the
      beneficial effect of tropisetron, we concluded that this effect of tropisetron is
      not mediated by alpha7nAChR.Our results showed that tropisetron treatment
      markedly ameliorated the experimental cisplatin induced-nephrotoxicity and this
      effect might be 5-HT3 receptor and alpha7nAChR independent.

PMID- 24905859
TI  - Emerging role of advanced glycation-end products (AGEs) in the pathobiology of
      eye diseases.
AB  - Advanced glycation end products (AGEs) have been implicated in vision loss
      associated with macula degeneration, cataract formation, diabetic retinopathy and
      glaucoma. This pathogenic potential is mainly attributed to their accumulation in
      ocular tissues where they mediate aberrant crosslinking of extracellular matrix
      proteins and disruption of endothelial junctional complexes that affects cell
      permeability, mediates angiogenesis and breakdown of the inner blood-retinal
      barrier. Furthermore, AGEs severely affect cellular metabolism by disrupting ATP
      production, enhancing oxidative stress and modulating gene expression of anti
      angiogenic and anti-inflammatory genes. Elucidation of AGE-induced mechanisms of
      action in different eye compartments will help in the understanding of the
      complex cellular and molecular processes associated with eye diseases. Several
      pharmaceutical agents with anti-glycating and anti-oxidant properties as well as
      AGE crosslink 'breakers' have been currently applied to eye diseases. The role of
      diet and the beneficial effects of certain nutriceuticals provide an alternative
      way to manage chronic visual disorders that affect the quality of life of
      millions of people. 

PMID- 24905860
TI  - Functional impairments characterizing mild, moderate, and severe hallux valgus.
AB  - OBJECTIVE: Hallux valgus (HV) has been linked to functional disability and
      increased risk of falls, but mechanisms underpinning functional disability are
      unclear. This study investigated functional performance, muscle strength, and
      plantar pressures in adults with mild, moderate, and severe HV compared to
      controls, while considering the influence of foot pain. METHODS: Sixty adults
      with HV (classified as mild, moderate, and severe on dorsalplantar radiographs)
      and 30 controls participated. Measures included hallux plantar flexion and
      abduction strength, walking performance, postural sway, and forefoot plantar
      pressures. Multivariate analysis of covariance and pairwise comparisons (P < 0.05
      after Bonferroni adjustment) were used to investigate differences between groups,
      adjusting for age, sex, body mass index, and foot pain. RESULTS: Hallux plantar
      flexion and abduction strength were significantly reduced in those with moderate
      (mean differences: plantar flexion -45.8 N, abduction -12.3 N; P < 0.001) and
      severe HV (plantar flexion -50.1 N; P < 0.001, abduction -11.2 N; P = 0.01)
      compared to controls. A significant reduction in hallux peak pressure and
      pressure-time integral was evident in moderate (peak pressure -90.8 kPa; P <
      0.001) and severe HV (peak pressure -106.2 kPa; P < 0.001) compared to controls.
      Those with severe HV also demonstrated increased mediolateral postural sway in
      single leg stance compared to controls (3.5 cm; P = 0.01). CONCLUSION: Moderate
      to severe HV is associated with reduced hallux plantar pressures and strength
      measures, while relatively normal function compared to controls was found in
      those with mild deformity. Greater understanding of specific functional deficits
      associated with different stages of HV will help inform clinical management and
      future research.

PMID- 24905861
TI  - Early oral feeding after emergency abdominal operations: another paradigm to be
      broken?
AB  - PURPOSE OF REVIEW: The scope of this article is to provide an updated review
      examining the role of early feeding in the postoperative period. RECENT FINDINGS:
      Guidelines for postoperative care after abdominal surgery have historically
      outlined the dogma of 'nil by mouth' until bowel movement returns, but they are
      currently questioned. This change in mindset, especially after colorectal
      surgery, was initiated with fast-track or enhanced recovery after surgery
      programs, which particularly led to an opioid-sparing strategy. Many randomized
      trials and meta-analyses suggested an absence of benefit in keeping patients 'nil
      by mouth'. Conversely, in elective abdominal surgery, improvement in comfort
      without increased morbidity is now demonstrated with a liberal strategy, and a
      recent meta-analysis even demonstrated a decrease in mortality. Early caloric
      hydration and chewing gum are the most acceptable actions with a high level of
      proof. After emergency surgery, few data are available but a similar strategy
      should probably be chosen with no obvious benefit from maintenance of fasting.
      SUMMARY: Early oral intake is possible after elective abdominal surgery and
      should be moderate and progressive to be well tolerated. Any sign of nausea may
      mean intestinal or gastric disturbance and is a caution not to pursue this
      policy. The strategy in emergency abdominal surgery still requires adequately
      powered, randomized controlled trials.

PMID- 24905862
TI  - Ghrelin: from discovery to cancer cachexia therapy.
AB  - PURPOSE OF REVIEW: Despite the high prevalence of cancer cachexia, a condition
      that negatively impacts patients' prognosis and quality of life, effective
      therapies are still lacking. Ghrelin is a peptide hormone involved in anabolic
      and homeostatic functions, whose mechanisms of action are still only partially
      clarified, but with promising positive effects in cancer cachexia. Recently, the
      therapeutic administration of ghrelin in cancer has been shown to counteract loss
      of body mass and function, including muscle, and we specifically focus on this
      novel evidence. RECENT FINDINGS: Recent research aimed at developing new
      pharmacological therapies to prevent muscle wasting has used ghrelin and
      molecules acting as synthetic ghrelin receptor agonists with different modalities
      of administration and with high selectivity for specific targeted tissues.
      Positive effects of these therapies were described in cancer cachexia and
      chemotherapy-induced muscle wasting. New insights into the mechanisms of action
      of ghrelin revealed how its pleiotropic effects should be ascribed both to
      systemic anti-inflammation effect and to muscle-specific action through the
      activation of the antiatrophic molecular cascade. SUMMARY: Growing interest
      arises from the identification of ghrelin as a valid and well tolerated
      therapeutic option to counteract structural and functional wasting derived from
      tumour growth.

PMID- 24905863
TI  - Efficacy of face masks and respirators in preventing upper respiratory tract
      bacterial colonization and co-infection in hospital healthcare workers - authors'
      reply.

PMID- 24905864
TI  - Smoking initiation among Israeli adolescents: a 24-year time-to-event analysis.
AB  - INTRODUCTION: Preventing smoking initiation will protect future generations from
      smoking-attributable death and disease. This study examines the correlates and
      patterns of initiation among Israeli youth using time-to-event analysis and other
      methods. METHODS: Twenty-four consecutive representative samples (1986-2009) of
      new military recruits (N=50,254) were analyzed. Cox regression and Kaplan-Meier
      analysis were used to identify factors associated with smoking initiation, and
      logistic regression was used to identify factors associated with smoking status.
      RESULTS: The most hazardous age for smoking initiation was seventeen, subsequent
      to the mean age of smoking initiation (males: 15.7, females: 16.0). Age of
      initiation and age of greatest hazard for initiation declined among recruits
      between the years 1986 and 2009. Earlier smoking initiation among boys and girls
      was significantly associated with low education levels (<12years) (males:
      HR=2.98, CI: [2.79, 3.18]; females: HR=3.35, CI: [2.96, 3.80]), low paternal
      education levels, Russian birthplace, and religion. Earlier initiation in boys
      was associated with high fitness levels and low/medium socio-economic status.
      Earlier initiation in girls was associated with being Western-born and ever-use
      of contraception. CONCLUSIONS: Smoking initiation among Israeli youth recruited
      to the armed forces is associated with individual and family characteristics,
      particularly low education levels. Time-to-event analysis complements traditional
      means of understanding smoking initiation by identifying ages at which initiation
      hazard is high.

PMID- 24905865
TI  - The effect of Chinese herbal medicine on non-biliogenic severe acute
      pancreatitis: a systematic review and meta-analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: More and more clinicians and researchers have
      realized that clinical trials are necessary to define clinical efficacy effect.
      Even though the number has been substantially growing for the past years, the
      finished and reported trials are limited. Nevertheless, those documented trials
      are important and precious, and comprehensive evaluation and analysis of them are
      warranted at current stage. Our goal was to evaluate the effect of Chinese herbal
      medicine (CHM) on non-biliogenic severe acute pancreatitis (SAP) by conducting a
      systematic review and meta-analysis of prospective randomized controlled studies.
      METHODS: Relevant studies were identified by PubMed, Cochrane Library, EMBASE,
      China Biomedical Database web (CBM), China National Knowledge Infrastructure
      Databases (CNKI), and Wanfang database up to 2014.Reference lists of retrieved
      articles were also reviewed. Two reviewers independently assessed studies for
      inclusion and extracted data. The main outcome data of trials were analyzed by
      using RevMan5.2. Odds ratio (OR) or mean difference (MD) with a 95% confidence
      interval (CI) was used as effect measure. Either a fixed or a random-effect model
      was used to evaluate the effect of CHM on non-biliogenic SAP. RESULTS: Twenty two
      prospective randomized controlled studies involving 1388 participants were
      included in the meta-analysis. CHM was tested to be more effective than reference
      group: Mortality [OR: 0.43, 95% CI (0.29, 0.64)], overall efficiency [OR: 4.0,
      95% CI (2.72, 5.89)], operability [OR: 0.313, 95% CI (0.21, 0.46)], rate of
      complications [OR: 0.37, 95% CI (0.27, 0.50)], Length of hospitalization [MD: 
      9.70, 95% CI (-12.88, -6.51)] compared with reference group. CONCLUSIONS: No
      serious adverse events were reported. This meta-analysis provides evidence
      suggesting that CHM seems to be an effective and safe treatment for people with
      non-biliogenic severe acute pancreatitis (SAP). However, the poor methodological
      quality of most of the trials means that we may be unable to reach a definitive
      conclusion. Hence, the effect of CHM in the treatment of non-biliogenic SAP
      warrants rigorously designed, multicentre, large-scale trials with higher quality
      worldwide.

PMID- 24905866
TI  - The traditional Chinese medicine prescription patterns of Sjogren's patients in
      Taiwan: a population-based study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCM), when given
      for symptom relief, have gained widespread popularity among Sjogren's patients.
      The aim of this study was to analyze the utilization of TCM among Sjogren's
      patients in Taiwan. MATERIALS AND METHODS: The usage, frequency of service, and
      the Chinese herbal products prescribed among Sjogren's patients were evaluated in
      a cohort of 1,000,000 beneficiaries recruited from the National Health Insurance
      Research Database. The logistic regression method was employed to estimate the
      odds ratios (ORs) for utilization of a TCM. RESULTS: More than 90% of Sjogren's
      patients received TCM out-patient services at least once during the study period.
      Patients with secondary Sjogren's syndrome were more likely to seek TCM treatment
      than those with primary Sjogren's syndrome. The aOR for those suffering from at
      least one rheumatologic disease was 1.56 (95% CI: 1.26-1.93), those with two
      rheumatologic diseases was 1.98 (95% CI: 1.29-3.04), while those with three or
      more rheumatologic diseases was 7.86 (95% CI: 1.09-56.58). Compared to Sjogren's
      patients who used no medical treatment, the aOR for those who took one type of
      conventional medication was 1.55 (95% CI: 1.25-1.92), those who took two types
      was 1.98 (95% CI: 1.60-2.47) while those who took three or more types was 2.91
      (95% CI: 2.20-3.84). Qi-Ju-Di-Huang-Wan (Lycium Berry, Chrysanthemum, and
      Rehmannia Pill) was the most frequently prescribed formula among Sjogren's
      patients. CONCLUSION: Qi-Ju-Di-Huang-Wan is the most commonly prescribed Chinese
      herbal formula for Sjogren's syndrome and its effects should be taken into
      account by healthcare providers.

PMID- 24905868
TI  - Safety and diagnostic accuracy of percutaneous biopsy in upper tract urothelial
      carcinoma.
AB  - OBJECTIVE: To assess the diagnostic accuracy and safety of percutaneous biopsy
      for upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: From 2002 to
      2013, 26 upper tract lesions in 24 patients (20 men; median [range] age 67.8
      [51.7-85.9] years) were percutaneously biopsied. Analysis was separated based on
      lesion appearance: (i) mass infiltrating renal parenchyma, (ii) filling defect in
      the collecting system, (iii) urothelial wall thickening. We tracked immediate
      complications and tract seeding on follow-up imaging. RESULTS: Of the 26 upper
      tract lesions, 15 (58%) were masses infiltrating the renal parenchyma (mean
      [range] size 5.4 [1.1-14.0] cm), six (23%) were urothelial wall thickenings (mean
      [range] size 0.8 [0.4-1.1] cm), and five (19%) were filling defects within the
      renal pelvis or calyx (mean [range] size 2.7 [1.0-4.6] cm). Definitive diagnosis
      of UTUC was made by biopsy in 22 of 26 lesions (85%). Biopsy characterised 14 of
      15 infiltrative masses and five of five filling defects; biopsy characterised
      three of six cases of urothelial wall thickening. CT follow-up was available for
      19 patients (73%) at a median (range) of 13.6 (1.0-98.9) months. Three patients
      (11%) developed recurrence in the nephrectomy bed at 5.6, 9.7, and 29.0 months
      after biopsy; none were attributed to tract seeding after independent review,
      because recurrence was remote from the biopsy site. CONCLUSION: Percutaneous
      biopsy is effective for diagnosis of UTUC, providing tissue diagnosis in 85% of
      cases. While case reports cite a risk of tract seeding, no cases of recurrence
      were definitely attributable to percutaneous biopsy. Thus, for upper tract
      urothelial lesions, which are not amenable to endoscopic biopsy, percutaneous
      biopsy is a safe and effective technique.

PMID- 24905867
TI  - The pharmacology of medieval sedatives: the "Great Rest" of the Antidotarium
      Nicolai.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Past practices of compound drugs from different
      plant ingredients enjoyed remarkable longevity over centuries yet are largely
      dismissed by modern science as subtherapeutic, lethal or fanciful. AIM OF THE
      STUDY: To examine the phytochemical content of a popular medieval opiate drug
      called the "Great Rest" and gauge the bioavailability and combined effects of its
      alkaloid compounds (morphine, codeine, hyoscyamine, scopolamine) on the human
      body according to modern pharmacokinetic and pharmacodynamic parameters
      established for these compounds. CALCULATIONS AND THEORY: We reviewed the most
      recent studies on the pharmacodynamics of morphine, codeine, hyoscyamine and
      scopolamine to ascertain plasma concentrations required for different
      physiological effects and applied these findings to dosage of the Great Rest.
      RESULTS: Given the proportional quantities of the alkaloid rich plants, we
      calculate the optimal dose of Great Rest to be 3.1+/-0.1-5.3+/-0.76 g and reveal
      that the lethal dose of Great Rest is double the therapeutic concentration where
      all three alkaloid compounds are biologically active. CONCLUSION: This study
      helps establish the effective dose (ED50), toxic dose (TD50) and lethal dose
      (LD50) rates for the ingestion of raw opium, henbane and mandrake, and describes
      their probable combined effects, which may be applied to similar types of pre
      modern pharmaceuticals to reveal the empirical logic behind past practices.

PMID- 24905869
TI  - Engineering orthogonality in supramolecular polymers: from simple scaffolds to
      complex materials.
AB  - Owing to the mastery exhibited by Nature in integrating both covalent and
      noncovalent interactions in a highly efficient manner, the quest to construct
      polymeric systems that rival not only the precision and fidelity but also the
      structure of natural systems has remained a daunting challenge. Supramolecular
      chemists have long endeavored to control the interplay between covalent and
      noncovalent bond formation, so as to examine and fully comprehend how function is
      predicated on self-assembly. The ability to reliably control polymer self
      assembly is essential to generate "smart" materials and has the potential to
      tailor polymer properties (i.e., viscosity, electronic properties) through fine
      tuning the noncovalent interactions that comprise the polymer architecture. In
      this context, supramolecular polymers have a distinct advantage over fully
      covalent systems in that they are dynamically modular, since noncovalent
      recognition motifs can be engineered to either impart a desired functionality
      within the overall architecture or provide a designed bias for the self-assembly
      process. In this Account, we describe engineering principles being developed and
      pursued by our group that exploit the orthogonal nature of noncovalent
      interactions, such as hydrogen bonding, metal coordination, and Coulombic
      interactions, to direct the self-assembly of functionalized macromolecules,
      resulting in the formation of supramolecular polymers. To begin, we describe our
      efforts to fabricate a modular poly(norbornene)-based scaffold via ring-opening
      metathesis polymerization (ROMP), wherein pendant molecular recognition elements
      based upon nucleobase-mimicking elements (e.g., thymine, diaminotriazine) or SCS
      Pd(II) pincer were integrated within covalent monofunctional or symmetrically
      functionalized polymers. The simple polymer backbones exhibited reliable self
      assembly with complementary polymers or small molecules. Within these systems, we
      applied successful protecting group strategies and template polymerizations to
      enhance the control afforded by ROMP. Main-chain-functionalized alternating block
      polymers based upon SCS-Pd(II) pincer-pyridine motifs were achieved through the
      combined exploitation of bimetallic initiators and supramolecularly
      functionalized terminators. Our initial design principles led to the successful
      fabrication of both main-chain- and side-chain-functionalized poly(norbornenes)
      via ROMP. Utilizing all of these techniques in concert led to engineering
      orthogonality while achieving complexity through the installation of multiple
      supramolecular motifs within the side chain, main chain, or both in our polymer
      systems. The exploitation and modification of design principles based upon
      functional ROMP initiators and terminators has resulted in the first synthesis of
      main-chain heterotelechelic polymers that self-assemble into A/B/C supramolecular
      triblock polymers composed of orthogonal cyanuric acid-Hamilton wedge and SCS
      Pd(II) pincer-pyridine motifs. Furthermore, supramolecular A/B/A triblock
      copolymers were realized through the amalgamation of functionalized monomers,
      ROMP initiators, and terminators. To date, this ROMP-fabricated system represents
      the only known method to afford polymer main chains and side chains studded with
      orthogonal motifs. We end by discussing the impetus to attain functional
      materials via orthogonal self-assembly. Collectively, our studies suggest that
      combining covalent and noncovalent bonds in a well-defined and precise manner is
      an essential design element to achieve complex architectures. The results
      discussed in this Account illustrate the finesse associated with engineering
      orthogonal interactions within supramolecular systems and are considered
      essential steps toward developing complex biomimetic materials with high
      precision and fidelity.

PMID- 24905870
TI  - A prospective analysis of airborne metal exposures and risk of Parkinson disease
      in the nurses' health study cohort.
AB  - BACKGROUND: Exposure to metals has been implicated in the pathogenesis of
      Parkinson disease (PD). OBJECTIVES: We sought to examine in a large prospective
      study of female nurses whether exposure to airborne metals was associated with
      risk of PD. METHODS: We linked the U.S. Environmental Protection Agency (EPA)'s
      Air Toxics tract-level data with the Nurses' Health Study, a prospective cohort
      of female nurses. Over the course of 18 years of follow-up from 1990 through
      2008, we identified 425 incident cases of PD. We examined the association of risk
      of PD with the following metals that were part of the first U.S. EPA collections
      in 1990, 1996, and 1999: arsenic, antimony, cadmium, chromium, lead, manganese,
      mercury, and nickel. To estimate hazard ratios (HRs) and 95% CIs, we used the Cox
      proportional hazards model, adjusting for age, smoking, and population density.
      RESULTS: In adjusted models, the HR for the highest compared with the lowest
      quartile of each metal ranged from 0.78 (95% CI: 0.59, 1.04) for chromium to 1.33
      (95% CI: 0.98, 1.79) for mercury. CONCLUSIONS: Overall, we found limited evidence
      for the association between adulthood ambient exposure to metals and risk of PD.
      The results for mercury need to be confirmed in future studies.

PMID- 24905871
TI  - Sound-producing voice prostheses: 150 years of research.
AB  - Advanced laryngeal cancer sometimes necessitates the removal of the complete
      larynx. This procedure involves suturing the trachea to an opening in the neck,
      the most disturbing consequence of which is the loss of voice. Since 1859,
      several devices have been developed for voice restoration, based mainly on a
      vibrating reed element. However, the resulting sound is very monotonous and thus
      unpleasant. Presently the most successful way of voice restoration is the
      placement of a one-way shunt valve in the tracheo-esophageal wall, thus
      preventing aspiration and allowing air to flow from the lungs to the esophagus,
      where soft tissues start to vibrate for substitute voicing. However, the quality
      of this voice is often poor. New artificial vocal folds to be placed within the
      shunt valve have been developed, and a membrane-principle concept appears very
      promising, owing to the self-cleaning construction and the high voice quality.
      Future developments will include electronic voice sources. Hopefully these
      developments will result in a high-quality voice, after 150 years of research. 

PMID- 24905873
TI  - Recent advances in nanoparticle-mediated siRNA delivery.
AB  - Inhibiting specific gene expression by short interfering RNA (siRNA) offers a new
      therapeutic strategy to tackle many diseases, including cancer, metabolic
      disorders, and viral infections, at the molecular level. The macromolecular and
      polar nature of siRNA hinders its cellular access to exert its effect.
      Nanoparticulate delivery systems can promote efficient intracellular delivery.
      Despite showing promise in many preclinical studies and potential in some
      clinical trials, siRNA has poor delivery efficiency, which continues to demand
      innovations, from carrier design to formulation, in order to overcome transport
      barriers. Previous findings for optimal plasmid DNA delivery cannot be
      generalized to siRNA delivery owing to significant discrepancy in size and subtle
      differences in chain flexibility between the two types of nucleic acids. In this
      review, we highlight the recent advances in improving the stability of siRNA
      nanoparticles, understanding their intracellular trafficking and release
      mechanisms, and applying judiciously the promising formulations to disease
      models. 

PMID- 24905872
TI  - Mechanosensing at the vascular interface.
AB  - Mammals are endowed with a complex set of mechanisms that sense mechanical forces
      imparted by blood flow to endothelial cells (ECs), smooth muscle cells, and
      circulating blood cells to elicit biochemical responses through a process
      referred to as mechanotransduction. These biochemical responses are critical for
      a host of other responses, including regulation of blood pressure, control of
      vascular permeability for maintaining adequate perfusion of tissues, and control
      of leukocyte recruitment during immunosurveillance and inflammation. This review
      focuses on the role of the endothelial surface proteoglycan/glycoprotein layer
      the glycocalyx (GCX)-that lines all blood vessel walls and is an agent in
      mechanotransduction and the modulation of blood cell interactions with the EC
      surface. We first discuss the biochemical composition and ultrastructure of the
      GCX, highlighting recent developments that reveal gaps in our understanding of
      the relationship between composition and spatial organization. We then consider
      the roles of the GCX in mechanotransduction and in vascular permeability control
      and review the prominent interaction of plasma-borne sphingosine-1 phosphate
      (S1P), which has been shown to regulate both the composition of the GCX and the
      endothelial junctions. Finally, we consider the association of GCX degradation
      with inflammation and vascular disease and end with a final section on future
      research directions. 

PMID- 24905874
TI  - From unseen to seen: tackling the global burden of uncorrected refractive errors.
AB  - Worldwide, more than one billion people suffer from poor vision because they do
      not have the eyeglasses they need. Their uncorrected refractive errors are a
      major cause of global disability and drastically reduce productivity, educational
      opportunities, and overall quality of life. The problem persists most prevalently
      in low-resource settings, even though prescription eyeglasses serve as a simple,
      effective, and largely affordable solution. In this review, we discuss barriers
      to obtaining, and approaches for providing, refractive eye care. We also
      highlight emerging technologies that are being developed to increase the
      accessibility of eye care. Finally, we describe opportunities that exist for
      engineers to develop new solutions to positively impact the diagnosis and
      treatment of correctable refractive errors in low-resource settings. 

PMID- 24905876
TI  - Electroporation-based technologies for medicine: principles, applications, and
      challenges.
AB  - When high-amplitude, short-duration pulsed electric fields are applied to cells
      and tissues, the permeability of the cell membranes and tissue is increased. This
      increase in permeability is currently explained by the temporary appearance of
      aqueous pores within the cell membrane, a phenomenon termed electroporation.
      During the past four decades, advances in fundamental and experimental
      electroporation research have allowed for the translation of electroporation
      based technologies to the clinic. In this review, we describe the theory and
      current applications of electroporation in medicine and then discuss current
      challenges in electroporation research and barriers to a more extensive spread of
      these clinical applications. 

PMID- 24905875
TI  - 3D biofabrication strategies for tissue engineering and regenerative medicine.
AB  - Over the past several decades, there has been an ever-increasing demand for organ
      transplants. However, there is a severe shortage of donor organs, and as a result
      of the increasing demand, the gap between supply and demand continues to widen. A
      potential solution to this problem is to grow or fabricate organs using
      biomaterial scaffolds and a person's own cells. Although the realization of this
      solution has been limited, the development of new biofabrication approaches has
      made it more realistic. This review provides an overview of natural and synthetic
      biomaterials that have been used for organ/tissue development. It then discusses
      past and current biofabrication techniques, with a brief explanation of the state
      of the art. Finally, the review highlights the need for combining vascularization
      strategies with current biofabrication techniques. Given the multitude of
      applications of biofabrication technologies, from organ/tissue development to
      drug discovery/screening to development of complex in vitro models of human
      diseases, these manufacturing technologies can have a significant impact on the
      future of medicine and health care. 

PMID- 24905878
TI  - Effects of biomechanical properties of the bone-implant interface on dental
      implant stability: from in silico approaches to the patient's mouth.
AB  - Dental implants have become a routinely used technique in dentistry for replacing
      teeth. However, risks of failure are still experienced and remain difficult to
      anticipate. Multiscale phenomena occurring around the implant interface determine
      the implant outcome. The aim of this review is to provide an understanding of the
      biomechanical behavior of the interface between a dental implant and the region
      of bone adjacent to it (the bone-implant interface) as a function of the
      interface's environment. First, we describe the determinants of implant stability
      in relation to the different multiscale simulation approaches used to model the
      evolution of the bone-implant interface. Then, we review the various aspects of
      osseointegration in relation to implant stability. Next, we describe the
      different approaches used in the literature to measure implant stability in vitro
      and in vivo. Last, we review various factors affecting the evolution of the bone
      implant interface properties. 

PMID- 24905877
TI  - Photoacoustic microscopy and computed tomography: from bench to bedside.
AB  - Photoacoustic imaging (PAI) of biological tissue has seen immense growth in the
      past decade, providing unprecedented spatial resolution and functional
      information at depths in the optical diffusive regime. PAI uniquely combines the
      advantages of optical excitation and those of acoustic detection. The hybrid
      imaging modality features high sensitivity to optical absorption and wide
      scalability of spatial resolution with the desired imaging depth. Here we first
      summarize the fundamental principles underpinning the technology, then highlight
      its practical implementation, and finally discuss recent advances toward clinical
      translation. 

PMID- 24905881
TI  - Parthenogenesis in a whitetip reef shark Triaenodon obesus involves a reduction
      in ploidy.
AB  - Genetic analysis of a female whitetip reef shark Triaenodon obesus and her
      stillborn pup, assumed to be of parthenogenetic origin, revealed that the pup was
      homozygous at all 24 nuclear-encoded microsatellites assayed, consistent with the
      idea that diploidy in the pup had been restored via terminal fusion. Flow
      cytometric analysis, however, indicated that the genome size of the pup was no
      more than half that of the mother, and microscopy revealed that nuclear volume
      was c. 1.73 times larger in the mother than in the pup. Together these data
      suggest that the pup was genetically haploid, developing directly from an
      unfertilized egg; as far as is known, this is the first observation of a
      spontaneously produced haploid vertebrate.

PMID- 24905880
TI  - Inertial focusing in microfluidics.
AB  - When Segre and Silberberg in 1961 witnessed particles in a laminar pipe flow
      congregating at an annulus in the pipe, scientists were perplexed and spent
      decades learning why such behavior occurred, finally understanding that it was
      caused by previously unknown forces on particles in an inertial flow. The advent
      of microfluidics opened a new realm of possibilities for inertial focusing in the
      processing of biological fluids and cellular suspensions and created a field that
      is now rapidly expanding. Over the past five years, inertial focusing has enabled
      high-throughput, simple, and precise manipulation of bodily fluids for a myriad
      of applications in point-of-care and clinical diagnostics. This review describes
      the theoretical developments that have made the field of inertial focusing what
      it is today and presents the key applications that will make inertial focusing a
      mainstream technology in the future. 

PMID- 24905879
TI  - Induced pluripotent stem cells for regenerative medicine.
AB  - With the discovery of induced pluripotent stem (iPS) cells, it is now possible to
      convert differentiated somatic cells into multipotent stem cells that have the
      capacity to generate all cell types of adult tissues. Thus, there is a wide
      variety of applications for this technology, including regenerative medicine, in
      vitro disease modeling, and drug screening/discovery. Although biological and
      biochemical techniques have been well established for cell reprogramming,
      bioengineering technologies offer novel tools for the reprogramming, expansion,
      isolation, and differentiation of iPS cells. In this article, we review these
      bioengineering approaches for the derivation and manipulation of iPS cells and
      focus on their relevance to regenerative medicine. 

PMID- 24905883
TI  - Atomistic simulations of TeO2-based glasses: interatomic potentials and molecular
      dynamics.
AB  - In this work we present for the first time empirical interatomic potentials that
      are able to reproduce TeO2-based systems. Using these potentials in classical
      molecular dynamics simulations, we obtained first results for the pure TeO2 glass
      structure model. The calculated pair distribution function is in good agreement
      with the experimental one, which indicates a realistic glass structure model. We
      investigated the short- and medium-range TeO2 glass structures. The local
      environment of the Te atom strongly varies, so that the glass structure model has
      a broad Q polyhedral distribution. The glass network is described as weakly
      connected with a large number of terminal oxygen atoms. 

PMID- 24905882
TI  - Successful implantation of a dual-chamber pacemaker in an ELBW infant for long QT
      syndrome.
AB  - Long QT syndromes encompass the most prevalent group of ion channelopathies. Long
      QT syndromes are predominantly familial and predispose the affected individual to
      ventricular arrhythmias and sudden death. Permanent pacemaker insertion for long
      QT syndrome is discouraged apart from younger patients exhibiting 2:1
      atrioventricular block. However, permanent pacemaker insertion is a relatively
      common procedure in neonates with atrioventricular block, and dual-chamber
      permanent pacemaker insertion in low birth weight infants is challenging. We
      describe the management of long QT syndrome - type 2 - presenting in an extremely
      preterm neonate including epicardial, dual-chamber permanent pacemaker insertion.

PMID- 24905885
TI  - Intracorporeal mesenteric division of the colon can make the specimen more
      suitable for natural orifice extraction.
AB  - Laparoscopic surgery combined with natural orifice specimen extraction (NOSE)
      avoids extra incisions to the abdominal wall and causes less pain and fewer wound
      complications, together with a shorter recovery and reduced time off from work.
      However, the size of the specimen is a limiting factor for NOSE. We describe a
      novel method for natural orifice colorectal specimen extraction that reduces the
      diameter of the specimen and provides an easier extraction through the vagina. A
      totally laparoscopic right hemicolectomy for a cecal adenocarcinoma 5 cm in
      diameter was performed on a 62-year-old woman. Ileocolic anastomosis was done
      intracorporeally. Before transvaginal extraction, the largest width of the
      specimen was measured as 12 cm. The bulky mesentery of the cecum that limited the
      NOSE was divided partially along the bowel with a LigaSureTM (Covidien, Boulder,
      CO) device. The largest width of the specimen was reduced to 9 cm, and the
      specimen was extracted without difficulty through the vagina in a bag. The stage
      of the tumor was pT3pN1. There was no recurrence with a 7-month follow-up.
      Transvaginal specimen extraction may fail because of the size of the specimen.
      Reduction of the width of the specimen by partial division of the mesocolon
      provides a high success rate for NOSE. This novel technique should be in the
      repertoire of laparoscopic colorectal surgeons.

PMID- 24905886
TI  - ACE-R or MMSE? A weighted comparison.

PMID- 24905887
TI  - Are we forcing people with dementia to receive care?

PMID- 24905888
TI  - Seroprevalence, genotypic distribution and potential risk factors of hepatitis B
      and C virus infections among adults in Siem Reap, Cambodia.
AB  - AIM: We investigated hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections among adults in Siem Reap, Cambodia, to consider the prevention
      strategy in cooperation with the Ministry of Health in Cambodia. METHODS:
      Serological tests for determining HBV and HCV infections and questionnaires were
      performed from 2010 to 2012 among the general population in the province of Siem
      Reap. Multivariate logistic regression analysis was conducted to clarify the
      factors related to HBV and HCV infections. RESULTS: There were 483 participants,
      comprising 194 men and 289 women (age range, 18-89 years). The prevalence of
      hepatitis B surface antigen was not very high at 4.6%, while anti-hepatitis B
      core (anti-HBc) was high at 38.5%. All HBV DNA samples were classified as
      genotype C. Anti-HBc showed the trend that the older the age, the higher the
      positive rate (P = 0.0002). The prevalence of HCV RNA and anti-HCV were 2.3% and
      5.8%, respectively. HCV RNA was detected in 39.3% of anti-HCV positive samples
      and most of them were classified as genotype 6 (54.5%) and 1 (27.3%). Remarkably,
      in multivariate logistic regression analysis, history of operation and blood
      transfusion were significantly associated with the positivity for HBV infection
      and HCV RNA, respectively. CONCLUSION: Our results showed that operation and
      blood transfusion were potential risk factors for HBV and HCV infection,
      respectively, and supposed that horizontal HBV transmission may be frequent in
      adults in Cambodia. Hence, for reducing HBV and HCV infections, it is necessary
      to improve the safety of blood and medical treatment.

PMID- 24905890
TI  - Averaging of diffusion tensor imaging direction-encoded color maps for localizing
      substantia nigra.
AB  - Diffusion tensor imaging (DTI) is a form of MRI that has been used extensively to
      map in vivo the white matter architecture of the human brain. It is also used for
      mapping subcortical nuclei because of its general sensitivity to tissue
      orientation differences and effects of iron accumulation on the diffusion signal.
      While DTI provides excellent spatial resolution in individual subjects, a
      challenge is visualizing consistent patterns of diffusion orientation across
      subjects. Here we present a simple method for averaging direction-encoded color
      anisotropy maps in standard space, explore this technique for visualizing the
      substantia nigra (SN) in relation to other midbrain structures, and show with
      signal-to-noise analysis that averaging improves the direction-encoded color
      signature. SN is distinguished on averaged maps from neighboring structures,
      including red nucleus (RN) and cerebral crus, and is proximal to SN location from
      existing brain atlases and volume of interest (VOI) delineation on individual
      scans using two blinded raters. 

PMID- 24905889
TI  - Intravenous xenogeneic transplantation of human adipose-derived stem cells
      improves left ventricular function and microvascular integrity in swine
      myocardial infarction model.
AB  - OBJECTIVES: The potential for beneficial effects of adipose-derived stem cells
      (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial
      ischemia (MI) has not been tested following intravenous delivery. METHODS:
      Surviving pigs following induction of MI were randomly assigned to 1 of 3
      different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7,
      15 * 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 * 10(7) ASCs/day for
      three consecutive days). Myocardial perfusion defect area and coronary flow
      reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in
      the absolute number of circulating CD4(+) T and CD8(+) T cells were measured.
      RESULTS: The increases in ejection fraction were significantly greater in both
      the SB and the DD groups compared to the placebo group (5.4 +/- 0.9%, 3.7 +/-
      0.7%, and -0.4 +/- 0.6%, respectively), and the decrease in the perfusion defect
      area was significantly greater in the SB group than the placebo group (-36.3 +/-
      1.8 and -11.5 +/- 2.8). CFR increased to a greater degree in the SB and the DD
      groups than in the placebo group (0.9 +/- 0.2, 0.8 +/- 0.1, and 0.2 +/- 0.2,
      respectively). The circulating number of CD8(+) T cells was significantly greater
      in the SB and DD groups than the placebo group at day 7 (3,687 +/- 317/uL, 3,454
      +/- 787/uL, and 1,928 +/- 457/uL, respectively). The numbers of small vessels
      were significantly greater in the SB and the DD groups than the placebo group in
      the peri-infarct area. CONCLUSIONS: Both intravenous SB and DD delivery of ASCs
      are effective modalities for the treatment of MI in swine. Intravenous delivery
      of ASCs, with its immunomodulatory and angiogenic effects, is an attractive
      noninvasive approach for myocardial rescue.

PMID- 24905892
TI  - Long-range electron transfer over graphene-based catalyst for high-performing
      oxygen reduction reactions: importance of size, N-doping, and metallic
      impurities.
AB  - N-doped carbon materials are considered as next-generation oxygen reduction
      reaction (ORR) catalysts for fuel cells due to their prolonged stability and low
      cost. However, the underlying mechanism of these catalysts has been only
      insufficiently identified, preventing the rational design of high-performing
      catalysts. Here, we show that the first electron is transferred into O2 molecules
      at the outer Helmholtz plane (ET-OHP) over a long range. This is in sharp
      contrast to the conventional belief that O2 adsorption must precede the ET step
      and thus that the active site must possess as good an O2 binding character as
      that which occurs on metallic catalysts. Based on the ET-OHP mechanism, the
      location of the electrode potential dominantly characterizes the ORR activity.
      Accordingly, we demonstrate that the electrode potential can be elevated by
      reducing the graphene size and/or including metal impurities, thereby enhancing
      the ORR activity, which can be transferred into single-cell operations with
      superior stability. 

PMID- 24905893
TI  - Development and application of an enzyme-linked immunosorbent assay (ELISA) for
      the quantification of amygdalin, a cyanogenic glycoside, in food.
AB  - Amygdalin is a member of the cyanogenic glycoside group of plant secondary
      metabolites capable of generating hydrogen cyanide under certain conditions. As a
      consequence, the cyanogenic glycosides have been associated with incidents of
      acute and subacute food poisoning. Specific antibodies were raised against an
      amygdalin-bovine serum albumin immunogen synthesized using a novel approach. The
      antibodies were used in a microtitration plate enzyme-linked immunosorbent assay
      (ELISA) for the quantification, for the first time, of amygdalin in commercially
      available foods. Correlation of results with high-performance liquid
      chromatography was very high (r = 0.983). The limit of detection of the
      immunoassay was 200 +/- 0.05 pg mL(-1), and the 50% inhibitory concentration of
      amygdalin was 50 +/- 0.02 ng mL(-1), making the ELISA particularly sensitive. 

PMID- 24905891
TI  - Coating of electrospun poly(lactic-co-glycolic acid) nanofibers with willemite
      bioceramic: improvement of bone reconstruction in rat model.
AB  - We have investigated the combination effects of bioceramics and poly(lactide-co
      glycolide) (PLGA) on bone reconstruction in calvarial critical size defects using
      a rat model. Willemite (Zn2SiO4) ceramics were prepared and coated on the surface
      of electrospun fabricated scaffolds. After scaffolds and nanoparticles
      characterization, osteoconductivity of the construct was analyzed using digital
      mammography, multislice spiral-computed tomography (MSCT) imaging, and
      histological analysis. Eight weeks after implantation, no sign of inflammation
      was observed at the site of the osseous defect. The results showed that the
      ceramics supported bone regeneration and highest bone reconstruction were
      observed in willemite-coated PLGA. This suggests that electrospun PLGA nanofibers
      coated with BG are potential candidate implants for bone tissue engineering
      applications.

PMID- 24905894
TI  - Hematopoietic stem cell aging.
AB  - Aging is organized in a hierarchy, in which aging of cells results in aged
      tissues, ultimately limiting lifespan. For organ systems that also in the adult
      depend on stem cells for tissue homeostasis like the hematopoietic system that
      forms immune cells, it is believed that aging of the stem cells strongly
      contributes to aging-associated dysfunction. In this review, we summarize current
      aspects on cellular and molecular mechanisms that are associated with aging of
      hematopoietic stem cells, the role of the stem cell niche for stem cell aging as
      well as novel and encouraging experimental approaches to attenuate aging of
      hematopoietic stem cells to target immunosenescence. 

PMID- 24905895
TI  - pH-responsive micelles based on caprylic acid.
AB  - Free fatty acids play a vital role as fuel for cells and in lipid metabolism.
      During lipid digestion in the gastrointestinal tract, triglycerides are
      hydrolyzed, resulting in free fatty acid and monoglyceride amphiphilic products.
      These components, together with bile salts, are responsible for the transport of
      lipids and poorly water-soluble nutrients and xenobiotics from the intestine into
      the circulatory system of the body. In this study, we show that the self-assembly
      of digestion products from medium-chain triglycerides (tricaprylin) in
      combination with bile salt and phospholipid is highly pH-responsive. Individual
      building blocks of caprylic acid within the mixed colloidal structures are mapped
      using a combination of small-angle X-ray and neutron scattering combined with
      both solvent contrast variation and selective deuteration. Modeling of the
      scattering data shows transitions in the size and shape of the micelles in
      combination with a transfer of the caprylic acid from the core of the micelles to
      the shell or into the bulk water upon increasing pH. The results help to
      understand the process of lipid digestion with a focus on colloidal structure
      formation and transformation for the delivery of triglyceride lipids and other
      hydrophobic functional molecules. 

PMID- 24905896
TI  - Colombian Children With Overweight and Obesity Need Additional Motivational
      Support at School to Perform Health-Enhancing Physical Activity.
AB  - AIMS: The aim of this study is to investigate associations of screen-time and
      physical activity (PA) with self-efficacy for PA, intrinsic motivation to PA and
      health-related quality of life (HRQoL) in Colombian schoolchildren from
      socioeconomically disadvantaged neighborhoods, and to compare these variables
      among children with normal-weight (NW), overweight (OW) and obesity (OB).
      METHODS: In 678 schoolchildren (age 10-14 years) screen-time (TV, video games,
      computer) and number of days being physically active >= 60 minutes were self
      reported. Multi-item scales were used to assess self-efficacy to PA and intrinsic
      motivation to PA. The KIDSCREEN-27 was used to assess HRQoL. RESULTS: Screen-time
      was associated with HRQoL in the school/learning environment dimension. Number of
      days being physically active was associated with self-efficacy for PA, intrinsic
      motivation for PA and with HRQoL concerning physical well-being, autonomy/parent
      relation and social support/peers. Group differences were found for days being
      physically active (OW = 2.8 and OB = 2.7 vs. NW = 3.3) but not for screen-time
      (NW = 5.0, OW = 4.7 and OB = 5.7 hrs.d-1). OW and OB scored lower on intrinsic
      motivation to PA than NW (OW = 19.2 and OB = 17.9 versus NW = 20.1). All 3 groups
      differed in physical well-being scores (NW = 50.3, OW = 48.1, OB = 40.6, P <
      .001). CONCLUSIONS: Schoolchildren with overweight and obesity from
      socioeconomically disadvantaged neighborhoods need additional motivational
      support to perform health-enhancing PA to experience higher physical well-being.

PMID- 24905897
TI  - AKT as a therapeutic target in multiple myeloma.
AB  - INTRODUCTION: Multiple myeloma remains an incurable malignancy with poor
      survival. Novel therapeutic approaches capable of improving outcomes in patients
      with multiple myeloma are urgently required. AKT is a central node in the
      phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin signaling pathway
      with high expression in advanced and resistant multiple myeloma. AKT contributes
      to multiple oncogenic functions in multiple myeloma which may be exploited
      therapeutically. Promising preclinical data has lent support for pursuing further
      development of AKT inhibitors in multiple myeloma. Lead drugs are now entering
      the clinic. AREAS COVERED: The rationale for AKT inhibition in multiple myeloma,
      pharmacological subtypes of AKT inhibitors in development, available results of
      clinical studies of AKT inhibitors and suitable drug partners for further
      development in combination with AKT inhibition in multiple myeloma are discussed.
      EXPERT OPINION: AKT inhibitors are a welcome addition to the armamentarium
      against multiple myeloma and promising clinical activity is being reported from
      ongoing trials in combination with established and/or novel treatment approaches.
      AKT inhibitors may be set to improve patient outcomes when used in combination
      with synergistic drug partners.

PMID- 24905900
TI  - 2014 Remington Lecture: making a difference.

PMID- 24905899
TI  - Epigenetic landscape of acute myelogenous leukemia--moving toward personalized
      medicine.
AB  - Acute myeloid leukemia (AML) is an aggressive hematologic cancer that is
      characterized by accumulation of immature myeloid cells in the blood and bone
      marrow. The malignant cells in AML have reduced capacity to mature fully, and
      often exhibit chromosomal abnormalities, defects in cell signaling, and abnormal
      cell cycle control. Genetic and epigenetic changes are implicated in the onset
      and progression of AML. While progress has been made in using genetic and
      epigenetic changes as prognostic features of AML, these findings have not yet
      been effectively translated into novel treatment strategies. Disappointingly,
      rates of recurrence in AML remain high and overall survival is poor. Research
      strategies should focus on developing a comprehensive landscape of genetic and
      epigenetic changes in individual patients with AML to expand the clinicians'
      therapeutic armamentarium and to individualize and optimize treatment.

PMID- 24905902
TI  - Nonmaternal care hours and temperament predict infants' proximity-seeking
      behavior and attachment subgroups.
AB  - Using the NICHD Early Childcare dataset (N=1281), this study examined whether
      infant temperament and the amount of time infants spend in nonmaternal care
      independently predict (1) the likelihood that they seek comfort from their mother
      when needed and (2) placement in a particular subgroup of infant-mother
      attachment patterns. Mothers reported the number of hours their infant spent in
      nonmaternal care each month and their infant's difficulty adapting to novel
      stimuli at 6 months. The degree to which 15-month-old infants seek comfort from
      their mother during reunion episodes in the Strange Situation was observed using
      two behavioral scales ("proximity seeking" and "contact maintaining"). Their
      average score forms the outcome variable of "proximity-seeking behavior." The
      other outcome variables were the subgroups of infant-mother attachment patterns:
      two subgroups for insecure babies (resistant and avoidant) and four subgroups for
      secure babies (B1, B2, B3, and B4). Easy adaptability to novel stimuli and long
      hours of nonmaternal care independently predicted a low level of proximity
      seeking behavior. These predictors also increased the likelihood of an insecure
      infant being classified as avoidant (vs. resistant). A secure infant with these
      same predictors was most likely to be classified as B1, followed by B2, and then
      B3, with B4 being the least likely classification. Although previous studies
      using the NICHD dataset found that hours of nonmaternal care had no main effect
      on infants' attachment security (vs. insecurity), this study demonstrates that
      hours of nonmaternal care predict the subcategories of infant-mother attachment.

PMID- 24905898
TI  - microRNA expression and biogenesis in cellular response to ionizing radiation.
AB  - Increasing evidence demonstrates that the expression levels of microRNAs (miRNAs)
      significantly change upon ionizing radiation (IR) and play a critical role in
      cellular response to IR. Although several radiation responsive miRNAs and their
      targets have been identified, little is known about how miRNAs expression and
      biogenesis is regulated by IR-caused DNA damage response (DDR). Hence, in this
      review, we summarize miRNA expression and biogenesis in cellular response to IR
      and mainly elucidate the regulatory mechanisms of miRNA expression and biogenesis
      from different aspects including ataxia-telangiectasia mutated (ATM) kinase,
      p53/p63/p73 family and other potential factors. Furthermore, we focus on
      DeltaNp73, which might be a potential regulator of miRNA expression and
      biogenesis in cellular response to IR. miRNAs could effectively activate the IR
      induced DDR and modulate the radiation response and cellular radiosensitivity,
      which have an important potential clinical application. Therefore, thoroughly
      understanding the regulatory mechanisms of miRNAs expression and biogenesis in
      radiation response will provide new insights for clinical cancer radiotherapy. 

PMID- 24905903
TI  - Roaming dynamics in radical addition-elimination reactions.
AB  - Radical addition-elimination reactions are a major pathway for transformation of
      unsaturated hydrocarbons. In the gas phase, these reactions involve formation of
      a transient strongly bound intermediate. However, the detailed mechanism and
      dynamics for these reactions remain unclear. Here we show, for reaction of
      chlorine atoms with butenes, that the Cl addition-HCl elimination pathway occurs
      from an abstraction-like Cl-H-C geometry rather than a conventional three-centre
      or four-centre transition state. Furthermore, access to this geometry is attained
      by roaming excursions of the Cl atom from the initially formed adduct. In effect,
      the alkene pi cloud serves to capture the Cl atom and hold it, allowing many
      subsequent opportunities for the energized intermediate to find a suitable
      approach to the abstraction geometry. These bimolecular roaming reactions are
      closely related to the roaming radical dynamics recently discovered to play an
      important role in unimolecular reactions. 

PMID- 24905901
TI  - Comparing methods for measuring peak look duration: are individual differences
      observed on screen-based tasks also found in more ecologically valid contexts?
AB  - Convergent research points to the importance of studying the ontogenesis of
      sustained attention during the early years of life, but little research hitherto
      has compared and contrasted different techniques available for measuring
      sustained attention. Here, we compare methods that have been used to assess one
      parameter of sustained attention, namely infants' peak look duration to novel
      stimuli. Our focus was to assess whether individual differences in peak look
      duration are stable across different measurement techniques. In a single cohort
      of 42 typically developing 11-month-old infants we assessed peak look duration
      using six different measurement paradigms (four screen-based, two naturalistic).
      Zero-order correlations suggested that individual differences in peak look
      duration were stable across all four screen-based paradigms, but no correlations
      were found between peak look durations observed on the screen-based and the
      naturalistic paradigms. A factor analysis conducted on the dependent variable of
      peak look duration identified two factors. All four screen-based tasks loaded
      onto the first factor, but the two naturalistic tasks did not relate, and mapped
      onto a different factor. Our results question how individual differences observed
      on screen-based tasks manifest in more ecologically valid contexts. 

PMID- 24905904
TI  - Comparison of Paired ROC Curves through a Two-Stage Test.
AB  - The area under the receiver operating characteristic (ROC) curve (AUC) is a
      popularly used index when comparing two ROC curves. Statistical tests based on it
      for analyzing the difference have been well developed. However, this index is
      less informative when two ROC curves cross and have similar AUCs. In order to
      detect differences between ROC curves in such situations, a two-stage
      nonparametric test that uses a shifted area under the ROC curve (sAUC), along
      with AUCs, is proposed for paired designs. The new procedure is shown,
      numerically, to be effective in terms of power under a wide range of scenarios;
      additionally, it outperforms two conventional ROC-type tests, especially when two
      ROC curves cross each other and have similar AUCs. Larger sAUC implies larger
      partial AUC at the range of low false-positive rates in this case. Because high
      specificity is important in many classification tasks, such as medical diagnosis,
      this is an appealing characteristic. The test also implicitly analyzes the
      equality of two commonly used binormal ROC curves at every operating point. We
      also apply the proposed method to synthesized data and two real examples to
      illustrate its usefulness in practice. 

PMID- 24905905
TI  - A nanodiamond/CNT-SiC monolith as a novel metal free catalyst for ethylbenzene
      direct dehydrogenation to styrene.
AB  - A novel nanodiamond/CNT-SiC monolith catalyst has been prepared by a facile two
      step approach. The as-synthesized monolith afforded high activity and stability
      for ethylbenzene direct dehydrogenation to styrene, showing its potential
      application as a metal free catalyst in gaseous catalytic reactions. 

PMID- 24905906
TI  - Insight into the coordination and the binding sites of Cu(2+) by the histidyl-6
      tag using experimental and computational tools.
AB  - His-tags are specific sequences containing six to nine subsequent histydyl
      residues, and they are used for purification of recombinant proteins by use of
      IMAC chromatography. Such polyhistydyl tags, often used in molecular biology, can
      be also found in nature. Proteins containing histidine-rich domains play a
      critical role in many life functions in both prokaryote and eukaryote organisms.
      Binding mode and the thermodynamic properties of the system depend on the
      specific metal ion and the histidine sequence. Despite the wide application of
      the His-tag for purification of proteins, little is known about the properties of
      metal-binding to such tag domains. This inspired us to undertake detailed studies
      on the coordination of Cu(2+) ion to hexa-His-tag. Experiments were performed
      using the potentiometric, UV-visible, CD, and EPR techniques. In addition,
      molecular dynamics (MD) simulations and density functional theory (DFT)
      calculations were applied. The experimental studies have shown that the Cu(2+)
      ion binds most likely to two imidazoles and one, two, or three amide nitrogens,
      depending on the pH. The structures and stabilities of the complexes for the
      Cu(2+)-Ac-(His)6-NH2 system using experimental and computational tools were
      established. Polymorphic binding states are suggested, with a possibility of the
      formation of alpha-helix structure induced by metal ion coordination. Metal ion
      is bound to various pairs of imidazole moieties derived from the tag with
      different efficiencies. The coordination sphere around the metal ion is completed
      by molecules of water. Finally, the Cu(2+) binding by Ac-(His)6-NH2 is much more
      efficient compared to other multihistidine protein domains. 

PMID- 24905908
TI  - Hidden asymmetry of ice.
AB  - Ice is a very complex and fundamentally important solid. In the present article,
      we review a new property of the hydrogen-bonded network in ice structures: an
      explicit nonequivalence of some antipodal configurations with the opposite
      direction of all hydrogen bonds (H-bonds). This asymmetry is most pronounced for
      the structures with considerable deviation of the H-bond network from the
      tetrahedral coordination. That is why we have investigated in detail four
      coordinated ice nanostructures with no outer "dangling" hydrogen atoms, namely,
      ice bilayers and ice nanotubes consisting of stacked n-membered rings. The reason
      for this H-bonding asymmetry is a fundamental nonequivalence of the arrangements
      of water molecules in some antipodal configurations with the opposite direction
      of all H-bonds. For these configurations, the overall pictures of deviations of
      the hydrogen bonds from linearity are qualitatively different. We consider the
      reversal of all H-bonds as an additional nongeometric operation of symmetry, more
      precisely antisymmetry. It is not easy to find the explicit breaking of the
      symmetry of hydrogen bonding (H-symmetry) in the variety of all configurations.
      Therefore, this asymmetry may be named hidden. 

PMID- 24905907
TI  - Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher
      respiratory quotient after aerobic exercise, but beta3-adrenoceptor 64R allele
      does not affect lipolysis: a human model.
AB  - Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are
      critical regulators of fat metabolism. CPT1B transports free acyl groups into
      mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their
      respective polymorphisms E531K and W64R have been identified as indicators of
      obesity in population studies. It is therefore important to understand the
      effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal
      muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of
      plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat
      oxidation (through the non-protein respiratory quotient). These parameters were
      measured in 37 participants during 30 min of aerobic exercise at approximately
      62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery,
      mean respiratory quotient values were higher in K allele carriers than in non
      carriers, indicating low post-exercise fatty acid oxidation rates. No significant
      differences in lipolysis or lipid oxidation were observed between R and W allele
      carriers of ADRB3 at any time during the aerobic load. The substitution of
      glutamic acid at position 531 by lysine in the CPT1B protein decreases the
      mitochondrial beta-oxidation pathway, which increases the non-protein respiratory
      quotient value during recovery from exercise. This may contribute to weight gain
      or reduced weight-loss following exercise. 

PMID- 24905909
TI  - Water consumption characteristics and water use efficiency of winter wheat under
      long-term nitrogen fertilization regimes in northwest China.
AB  - Water shortage and nitrogen (N) deficiency are the key factors limiting
      agricultural production in arid and semi-arid regions, and increasing
      agricultural productivity under rain-fed conditions often requires N management
      strategies. A field experiment on winter wheat (Triticum aestivum L.) was begun
      in 2004 to investigate effects of long-term N fertilization in the traditional
      pattern used for wheat in China. Using data collected over three consecutive
      years, commencing five years after the experiment began, the effects of N
      fertilization on wheat yield, evapotranspiration (ET) and water use efficiency
      (WUE, i.e. the ratio of grain yield to total ET in the crop growing season) were
      examined. In 2010, 2011 and 2012, N increased the yield of wheat cultivar
      Zhengmai No. 9023 by up to 61.1, 117.9 and 34.7%, respectively, and
      correspondingly in cultivar Changhan No. 58 by 58.4, 100.8 and 51.7%. N-applied
      treatments increased water consumption in different layers of 0-200 cm of soil
      and thus ET was significantly higher in N-applied than in non-N treatments. WUE
      was in the range of 1.0-2.09 kg/m3 for 2010, 2011 and 2012. N fertilization
      significantly increased WUE in 2010 and 2011, but not in 2012. The results
      indicated the following: (1) in this dryland farming system, increased N
      fertilization could raise wheat yield, and the drought-tolerant Changhan No. 58
      showed a yield advantage in drought environments with high N fertilizer rates;
      (2) N application affected water consumption in different soil layers, and
      promoted wheat absorbing deeper soil water and so increased utilization of soil
      water; and (3) comprehensive consideration of yield and WUE of wheat indicated
      that the N rate of 270 kg/ha for Changhan No. 58 was better to avoid the risk of
      reduced production reduction due to lack of precipitation; however, under
      conditions of better soil moisture, the N rate of 180 kg/ha was more economic. 

PMID- 24905910
TI  - An examination of the relationships among uncertainty, appraisal, and information
      seeking behavior proposed in uncertainty management theory.
AB  - Uncertainty management theory (UMT; Brashers, 2001, 2007) is rooted in the
      assumption that, as opposed to being inherently negative, health-related
      uncertainty is appraised for its meaning. Appraisals influence subsequent
      behaviors intended to manage uncertainty, such as information seeking. This study
      explores the connections among uncertainty, appraisal, and information-seeking
      behavior proposed in UMT. A laboratory study was conducted in which participants
      (N = 157) were primed to feel and desire more or less uncertainty about skin
      cancer and were given the opportunity to search for skin cancer information using
      the World Wide Web. The results show that desired uncertainty level predicted
      appraisal intensity, and appraisal intensity predicted information-seeking depth
      although the latter relationship was in the opposite direction of what was
      expected. 

PMID- 24905911
TI  - Ecological speciation in Nolina parviflora (Asparagaceae): lacking spatial
      connectivity along of the Trans-Mexican Volcanic Belt.
AB  - The hypothesis of ecological speciation states that as populations diverge in
      different niches, reproductive isolation evolves as a by-product of adaptation to
      these different environments. In this context, we used Nolina parviflora as a
      model to test if this species evolved via ecological speciation and to explore
      current and historical gene flow among its populations. Nolina parviflora is a
      montane species endemic to Mexico with its geographical distribution restricted
      largely to the Trans-Mexican Volcanic Belt. This mountain range is one of the
      most complex geological regions in Mexico, having undergone volcanism from the
      mid-Miocene to the present. Ecologically, the Trans-Mexican Volcanic Belt
      possesses different types of vegetation, including tropical dry forest; oak,
      pine, pine-oak, and pine-juniper forests; and xerophytic scrub--all of which
      maintain populations of N. parviflora. Using species distribution models,
      climatic analyses, spatial connectivity and morphological comparisons, we found
      significant differences in climatic and morphological variables between
      populations of N. parviflora in two distinct Trans-Mexican Volcanic Belt regions
      (east vs. west). This could mean that the geographically isolated populations
      diverged from one another via niche divergence, indicating ecological speciation.
      Spatial connectivity analysis revealed no connectivity between these regions
      under the present or last glacial maximum climate models, indicating a lack of
      gene flow between the populations of the two regions. The results imply that
      these populations may encompass more than a single species.

PMID- 24905912
TI  - Efficacy of telbivudine compared with entecavir in hepatitis B virus-related
      cirrhosis: 2 year follow-up data.
AB  - BACKGROUND & AIMS: Entecavir (ETV) is effective in the treatment of chronic
      hepatitis B virus (HBV) infections, even in patients with underlying cirrhosis.
      However, there is little information on the effect of telbivudine (TBV) in
      chronic hepatitis B patients with cirrhosis.This study compared the antiviral
      efficacy of TBV and ETV in HBV-related cirrhosis. METHODS: We consecutively
      enrolled 151 treatment-naive patients with HBV-related cirrhosis who started
      antiviral therapy with TBV (n = 61) or ETV (n = 90). RESULTS: After 24 months of
      treatment, per-protocol analysis showed similar virological response rates (HBV
      DNA <20 IU/ml) in the TBV group (80.6%, 25/31) and in the ETV group (90.2%,
      74/82) (P = 0.167). However, intention-to-treat analysis showed lower virological
      response rates in the TBV group (41.7%, 25/60) than in the ETV group (83.1%,
      74/89) (P = 0.001). Mean reduction in HBV DNA levels was greater in the ETV group
      (-3.72 +/- 1.94 vs. -4.87 +/- 1.57 respectively, P = 0.001). Serologic and
      biochemical response rates at month 24 did not differ significantly between the
      groups. Child-Turcotte-Pugh score was significantly improved after 24 months
      compared to the pretreatment state without difference between the groups. During
      24 months of therapy, 15 patients (27.3%) showed antiviral resistance to TBV
      while no resistance (0%) was reported in the ETV group (P = 0.001). CONCLUSIONS:
      Compared to ETV, TBV therapy shows lower efficacy in viral suppression and higher
      risk of antiviral resistance despite comparable effect on improvement of hepatic
      function for the treatment of HBV-related cirrhosis.

PMID- 24905913
TI  - Automated assessment of beta-cell area and density per islet and patient using
      TMEM27 and BACE2 immunofluorescence staining in human pancreatic beta-cells.
AB  - In this study we aimed to establish an unbiased automatic quantification pipeline
      to assess islet specific features such as beta-cell area and density per islet
      based on immunofluorescence stainings. To determine these parameters, the in vivo
      protein expression levels of TMEM27 and BACE2 in pancreatic islets of 32 patients
      with type 2 diabetes (T2D) and in 28 non-diabetic individuals (ND) were used as
      input for the automated pipeline. The output of the automated pipeline was first
      compared to a previously developed manual area scoring system which takes into
      account the intensity of the staining as well as the percentage of cells which
      are stained within an islet. The median TMEM27 and BACE2 area scores of all
      islets investigated per patient correlated significantly with the manual scoring
      and with the median area score of insulin. Furthermore, the median area scores of
      TMEM27, BACE2 and insulin calculated from all T2D were significantly lower
      compared to the one of all ND. TMEM27, BACE2, and insulin area scores correlated
      as well in each individual tissue specimen. Moreover, islet size determined by
      costaining of glucagon and either TMEM27 or BACE2 and beta-cell density based
      either on TMEM27 or BACE2 positive cells correlated significantly. Finally, the
      TMEM27 area score showed a positive correlation with BMI in ND and an inverse
      pattern in T2D. In summary, automated quantification outperforms manual scoring
      by reducing time and individual bias. The simultaneous changes of TMEM27, BACE2,
      and insulin in the majority of the beta-cells suggest that these proteins reflect
      the total number of functional insulin producing beta-cells. Additionally, beta
      cell subpopulations may be identified which are positive for TMEM27, BACE2 or
      insulin only. Thus, the cumulative assessment of all three markers may provide
      further information about the real beta-cell number per islet. 

PMID- 24905915
TI  - Lysine residues at the first and second KTKEGV repeats mediate alpha-Synuclein
      binding to membrane phospholipids.
AB  - While alpha-Synuclein (alpha-Syn) is mainly detected as a cytosolic protein, a
      portion of it is recovered bound to membranes. It is suggested that binding to
      membrane phospholipids controls alpha-Syn structure, physiology and pathogenesis.
      We aimed at investigating the role, of the positive charged lysine residues at
      the KTKEGV repeat motif, in mediating alpha-Syn associations with membrane
      phospholipids and in alpha-Syn oligomerization and aggregation. Specifically, two
      positive lysine (K) residues were replaced with two negative glutamic acid (E)
      residues at either the first or second KTKEGV repeat motifs. The effect of these
      mutations on membrane binding was determined by a quantitative phospholipid ELISA
      assay and compared to wild-type alpha-Syn and to the Parkinson's disease-causing
      mutations, A30P, E46K and A53T. We found that the K to E substitutions affected
      alpha-Syn binding to phospholipids. In addition, K to E substitutions resulted in
      a dramatically lower level of soluble alpha-Syn oligomers and larger
      intracellular inclusions. Together, our results suggest a critical role for
      lysine residues at the N-terminal repeat domain in the pathophysiology of alpha
      Syn. 

PMID- 24905916
TI  - Trail resistance induces epithelial-mesenchymal transition and enhances
      invasiveness by suppressing PTEN via miR-221 in breast cancer.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively
      induce apoptosis of cancer cells and is verified effective to various cancers.
      However, a variety of breast cancer cell lines are resistant to TRAIL and the
      mechanisms of resistance are largely unknown. In our present experiment, we
      successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL
      resistant cell line. We found resistance to TRAIL could induce epithelial
      mesenchymal transition (EMT) and enhance invasiveness. We further demonstrated
      PTEN was down-regulated in TRAIL-resistant cells. Silencing miR-221, PTEN
      expression was up-regulated, the process of EMT could be reversed, and the
      ability of migration and invasion were correspondingly weakened. We also
      demonstrated knockdown of miR-221 could reverse resistance to TRAIL partially by
      targeting PTEN. Our findings suggest that resistance to TRAIL could induce EMT
      and enhance invasiveness by suppressing PTEN via miR-221. Re-expression of miR
      221 or targeting PTEN might serve as potential therapeutic approaches for the
      treatment of Trail-resistant breast cancer. 

PMID- 24905917
TI  - Activation of the MAPK11/12/13/14 (p38 MAPK) pathway regulates the transcription
      of autophagy genes in response to oxidative stress induced by a novel copper
      complex in HeLa cells.
AB  - Transition metal copper (Cu) can exist in oxidized or reduced states in cells,
      leading to cytotoxicity in cancer cells through oxidative stress. Recently,
      copper complexes are emerging as a new class of anticancer compounds. Here, we
      report that a novel anticancer copper complex (HYF127c/Cu) induces oxidative
      stress-dependent cell death in cancer cells. Further, transcriptional analysis
      revealed that oxidative stress elicits broad transcriptional changes of genes, in
      which autophagy-related genes are significantly changed in HYF127c/Cu-treated
      cells. Consistently, autophagy was induced in HYF127c/Cu-treated cells and
      inhibitors of autophagy promoted cell death induced by HYF127c/Cu. Further
      analysis identified that the MAPK11/12/13/14 (formerly known as p38 MAPK) pathway
      was also activated in HYF127c/Cu-treated cells. Meanwhile, the MAPK11/12/13/14
      inhibitor SB203580 downregulated autophagy by inhibiting the transcription of the
      autophagy genes MAP1LC3B, BAG3, and HSPA1A, and promoted HYF127c/Cu-induced cell
      death. These data suggest that copper-induced oxidative stress will induce
      protective autophagy through transcriptional regulation of autophagy genes by
      activation of the MAPK11/12/13/14 pathway in HeLa cells. 

PMID- 24905918
TI  - Static stretching alters neuromuscular function and pacing strategy, but not
      performance during a 3-km running time-trial.
AB  - PURPOSE: Previous studies report that static stretching (SS) impairs running
      economy. Assuming that pacing strategy relies on rate of energy use, this study
      aimed to determine whether SS would modify pacing strategy and performance in a 3
      km running time-trial. METHODS: Eleven recreational distance runners performed a)
      a constant-speed running test without previous SS and a maximal incremental
      treadmill test; b) an anthropometric assessment and a constant-speed running test
      with previous SS; c) a 3-km time-trial familiarization on an outdoor 400-m track;
      d and e) two 3-km time-trials, one with SS (experimental situation) and another
      without (control situation) previous static stretching. The order of the sessions
      d and e were randomized in a counterbalanced fashion. Sit-and-reach and drop jump
      tests were performed before the 3-km running time-trial in the control situation
      and before and after stretching exercises in the SS. Running economy, stride
      parameters, and electromyographic activity (EMG) of vastus medialis (VM), biceps
      femoris (BF) and gastrocnemius medialis (GA) were measured during the constant
      speed tests. RESULTS: The overall running time did not change with condition (SS
      11:35+/-00:31 s; control 11:28+/-00:41 s, p = 0.304), but the first 100 m was
      completed at a significantly lower velocity after SS. Surprisingly, SS did not
      modify the running economy, but the iEMG for the BF (+22.6%, p = 0.031), stride
      duration (+2.1%, p = 0.053) and range of motion (+11.1%, p = 0.0001) were
      significantly modified. Drop jump height decreased following SS (-9.2%, p =
      0.001). CONCLUSION: Static stretch impaired neuromuscular function, resulting in
      a slow start during a 3-km running time-trial, thus demonstrating the fundamental
      role of the neuromuscular system in the self-selected speed during the initial
      phase of the race.

PMID- 24905920
TI  - The dynamics of democracy, development and cultural values.
AB  - Over the past decades many countries have experienced rapid changes in their
      economies, their democratic institutions and the values of their citizens.
      Comprehensive data measuring these changes across very different countries has
      recently become openly available. Between country similarities suggest common
      underlying dynamics in how countries develop in terms of economy, democracy and
      cultural values. We apply a novel Bayesian dynamical systems approach to identify
      the model which best captures the complex, mainly non-linear dynamics that
      underlie these changes. We show that the level of Human Development Index (HDI)
      in a country drives first democracy and then higher emancipation of citizens.
      This change occurs once the countries pass a certain threshold in HDI. The data
      also suggests that there is a limit to the growth of wealth, set by higher
      emancipation. Having reached a high level of democracy and emancipation,
      societies tend towards equilibrium that does not support further economic growth.
      Our findings give strong empirical evidence against a popular political science
      theory, known as the Human Development Sequence. Contrary to this theory, we find
      that implementation of human-rights and democratisation precede increases in
      emancipative values. 

PMID- 24905921
TI  - HCV infection enhances Th17 commitment, which could affect the pathogenesis of
      autoimmune diseases.
AB  - BACKGROUND: Various kinds of autoimmune diseases have been reported to have a
      significant relationship with persistent hepatitis c virus (HCV) infection and
      Th17 cells. Previously, our group reported that the existence of HCV in T
      lymphocytes could affect the development of CD4+ helper T cells and their
      proliferation, in addition to the induction of immunoglobulin hyper-mutation.
      METHODS: Therefore, we analyzed the relationship between persistent infection of
      HCV and the mechanism of Th17 cell induction ex vivo and in vitro. RESULTS: The
      prevalence of autoimmune-related diseases in chronic hepatitis c patients (CH-C)
      was significantly higher than in other types of chronic hepatitis (hepatitis B
      and NASH). A significantly higher frequency of IL6 and TGF-beta double-high
      patients was detected in CH-C than in other liver diseases. Moreover, these
      double-high patients had significantly higher positivity of anti-nuclear
      antibody, cryoglobulinemia, and lymphotropic HCV and higher amounts of IL1-beta,
      IL21, IL23. In addition to the previously reported lymphotropic SB-HCV strain, we
      found a novel, genotype 1b lymphotropic HCV (Ly-HCV), by deep sequencing
      analysis. Lymphotropic-HCV replication could be detected in the lymphoid cells
      with various kinds of cytokine-conditions including IL1beta, IL23, IL6 and TGF
      beta in vitro. Infection by HCV could significantly enhance the development of
      Th17 cells. The HCV protein responsible for inducing the Th17 cells was HCV-Core
      protein, which could enhance the STAT-3 signaling and up-regulate the expression
      of RORgammat as a Th17 master gene. CONCLUSION: Infection by lymphotropic HCV
      might enhance the Th17 development and contribute to understanding the
      pathogenesis of autoimmune-related diseases.

PMID- 24905924
TI  - Bayesian Two-Part Tobit Models with Left-Censoring, Skewness, and Nonignorable
      Missingness.
AB  - In a longitudinal HIV/AIDS study with response data, observations may be missing
      because of patient dropouts due to drug intolerance or other problems, resulting
      in nonignorable missing data. In addition to nonignorable missingness, there are
      also problems of skewness and left-censoring in the response variable because of
      a lower limit of detection (LOD). There has been relatively little work published
      simultaneously dealing with these features of longitudinal data. In particular,
      one of the features may sometimes be the existence of a larger proportion of left
      censored data falling below LOD than expected under a usually assumed log-normal
      distribution. When this happens, an alternative model that can account for a high
      proportion of censored data should be considered. We present an extension of the
      random effects Tobit model that incorporates a mixture of true undetectable
      observations and the values from a skew-normal distribution for an outcome with
      left-censoring, skewness, and nonignorable missingness. A unifying modeling
      approach is used to assess the impact of left-censoring, skewness, nonignorable
      missingness and measurement error in covariates on a Bayesian inference. The
      proposed methods are illustrated using real data from an AIDS clinical study. 

PMID- 24905922
TI  - Comparative analysis of gene expression data reveals novel targets of senescence
      associated microRNAs.
AB  - In the last decades, cellular senescence is viewed as a complex mechanism
      involved in different processes, ranging from tumor suppression to induction of
      age-related degenerative alterations. Senescence-inducing stimuli are myriad and,
      recently, we and others have demonstrated the role exerted by microRNAs in the
      induction and maintenance of senescence, by the identification of a subset of
      Senescence-Associated microRNAs (SAmiRs) up-regulated during replicative or
      stress-induced senescence and able to induce a premature senescent phenotype when
      over-expressed in human primary cells. With the intent to find novel direct
      targets of two specific SAmiRs, SAmiR-494 and -486-5p, and cellular pathways
      which they are involved in, we performed a comparative analysis of gene
      expression profiles available in literature to select genes down-regulated upon
      replicative senescence of human primary fibroblasts. Among them, we searched for
      SAmiR's candidate targets by analyzing with different target prediction
      algorithms their 3'UTR for the presence of SAmiR-binding sites. The expression
      profiles of selected candidates have been validated on replicative and stress
      induced senescence and the targeting of the 3'UTRs was assessed by luciferase
      assay. Results allowed us to identify Cell Division Cycle Associated 2 (CDCA2)
      and Inhibitor of DNA binding/differentiation type 4 (ID4) as novel targets of
      SAmiR-494 and SAmiR-486-5p, respectively. Furthermore, we demonstrated that the
      over-expression of CDCA2 in human primary fibroblasts was able to partially
      counteract etoposide-induced senescence by mitigating the activation of DNA
      Damage Response. 

PMID- 24905926
TI  - Dental laser phototherapy.

PMID- 24905927
TI  - Cellular effect of low-level laser therapy on the rate and quality of bone
      formation in mandibular distraction osteogenesis.
AB  - OBJECTIVE: Therapeutic lasers have been shown to influence bone physiology and
      repair. The aim of the present investigation was to evaluate the use of a GaAlAs
      (lambda:810 nm) laser in distraction osteogenesis. BACKGROUND DATA: To reduce
      problems associated with distraction osteogenesis and shorten the time required
      for treatment, it is desirable to accelerate the process of bone formation.
      MATERIALS AND METHODS: Eighteen male rabbits underwent corticotomy of mandibular
      body, and customized distraction devices were inserted. After a 5-day latency
      period, the mandibles were lengthened by 0.5 mm/day for 10 days. The rabbits were
      divided into two groups. A GaAlAs (lambda: 810 nm) laser beam with the parameters
      power (P), 200 mW; energy density (ED), 3 J/cm(2); time (T), 7.5 sec; power
      density (PD) 400 mW/cm(2); energy (E) 1.5 J and spot diameter, 0.8 mm was
      directed medially and laterally in the study group; the control group received no
      laser treatment. The exposure continued with six more doses every other day.
      Three rabbits from each of the two groups were euthanized on the 10th, 20th, and
      40th days post-distraction (consolidation) period. RESULTS: Both light microscopy
      and scanning electron microscopic (SEM) analysis showed significant improvement
      in new bone formation in the study group at the 10th and 20th days compared with
      the control group, but the difference was more prominent on the 10th day. By the
      40th day, there were no significant differences between the two groups.
      CONCLUSIONS: This study shows that a low-level GaAlAs (lambda:810 nm; P, 200 mW)
      laser hastens new bone formation only in the early stages of the consolidation
      period in distraction osteogenesis, and has no significant effect in later
      stages.

PMID- 24905928
TI  - Effects of low-level laser irradiation on the pathogenicity of Candida albicans:
      in vitro and in vivo study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of low-level
      laser irradiation (LLLI) on the in vitro growth characteristics and in vivo
      pathogenicity of Candida albicans in a murine model in the absence of a
      photosensitizer. BACKGROUND DATA: C. albicans is an opportunistic commensal
      organism that causes a wide variety of diseases in human beings, ranging from
      superficial infections to life-threatening invasive candidiasis. The incidence of
      C. albicans infection is increasing, because of the greater frequency of acquired
      immunodeficiency conditions. A high recurrence rate has been reported for
      vulvovaginal and oral candidiasis, despite the best available treatments.
      Therefore, the search for new treatment modalities seems quite rational. METHODS:
      Candida culture plates were exposed to common clinical energies of LLLI: 3, 5,
      10, and 20 J at 685 nm (BTL Laser 5000, Medicinos Projektai, Czech Republic,
      Prague, max power output 50 mW) and 3, 5, 10, 30, and 50 J at 830 nm (BTL Laser
      5000, Medicinos Projektai, Czech Republic, Prague, max power output 400 mW).
      RESULTS: Following LLLI with energies >10 J at both 685 and 830 nm wavelengths,
      statistically significant effects were observed in vitro on the turbidimetric
      growth kinetics of C. albicans and in vivo on the survival rate of infected mice
      (p value <= 0.05). Therefore, this energy could be considered a threshold for
      clinical investigation. CONCLUSIONS: Translating our data into the clinical
      setting, it can be proposed that a direct laser-based approach without using a
      photosensitizing dye can significantly reduce the pathogenicity of Candida
      albicans. It can also be concluded that laser light at specific wavelengths could
      be a possible promising novel treatment for superficial and mucocutaneous C.
      albicans infections.

PMID- 24905925
TI  - ZO-1 and ZO-2 are required for extra-embryonic endoderm integrity, primitive
      ectoderm survival and normal cavitation in embryoid bodies derived from mouse
      embryonic stem cells.
AB  - The Zonula Occludens proteins ZO-1 and ZO-2 are cell-cell junction-associated
      adaptor proteins that are essential for the structural and regulatory functions
      of tight junctions in epithelial cells and their absence leads to early embryonic
      lethality in mouse models. Here, we use the embryoid body, an in vitro peri
      implantation mouse embryogenesis model, to elucidate and dissect the roles ZO-1
      and ZO-2 play in epithelial morphogenesis and de novo tight junction assembly.
      Through the generation of individual or combined ZO-1 and ZO-2 null embryoid
      bodies, we show that their dual deletion prevents tight junction formation,
      resulting in the disorganization and compromised barrier function of embryoid
      body epithelial layers. The disorganization is associated with poor microvilli
      development, fragmented basement membrane deposition and impaired cavity
      formation, all of which are key epithelial tissue morphogenetic processes.
      Expression of Podocalyxin, which positively regulates the formation of microvilli
      and the apical membrane, is repressed in embryoid bodies lacking both ZO-1 and ZO
      2 and this correlates with an aberrant submembranous localization of Ezrin. The
      null embryoid bodies thus give an insight into how the two ZO proteins influence
      early mouse embryogenesis and possible mechanisms underlying the embryonic lethal
      phenotype. 

PMID- 24905929
TI  - Placebo-controlled investigation of low-level laser therapy to treat carpal
      tunnel syndrome.
AB  - OBJECTIVE: This study investigated the short-term efficacy of low-level laser
      therapy (LLLT) in patients with mild to moderate carpal tunnel syndrome (CTS),
      lasting for <1 year. METHODS: Seventy-nine patients with CTS were included in
      this double-blind, placebo-controlled study, and randomly divided in two
      treatment groups: Experimental group (EG), active laser group (40 patients); and
      control group (CG), placebo (sham) laser group (39 patients). A GaAlAs diode
      laser [780 nm, 30 mW continuous wave (CW), 0.785 cm(2), 38.2 mW/cm(2)] was
      applied in contact with four points perpendicularly to the skin over the carpal
      tunnel area for 90 sec per point (2.7 J, 3.4 J/cm(2)/point). Both groups were
      treated five times per week, once a day over 2 weeks, followed by 10 treatments
      every other day for 3 weeks, that is, for a total of 20 treatments. Clinical
      assessment, including visual analogue scale (VAS) pain rating, Tinel's sign, and
      median nerve conduction studies (NCSs) were evaluated before, and 3 weeks after,
      the last LLLT treatment. RESULTS: Significant reduction in pain, reduction in the
      percentage of patients with a positive Tinel's sign, and shortening of sensory
      and motor latency time in the NCS examination was observed in the experimental
      LLLT group (but not in the control group). CONCLUSIONS: This study has observed
      and documented the statistically significant short-term effects of LLLT on CTS
      patients in comparison with a placebo group. The results support this conclusion,
      especially if the LLLT is applied in the earlier stages of CTS, and with mild to
      moderate cases.

PMID- 24905931
TI  - Subcellular toxicity of gold nanoparticles irradiated with 532 nm pulsed laser.
AB  - OBJECTIVE: Prior to plasmonic photothermal therapy, involving heating of gold
      nanoparticles (GNPs) by laser, we explored some subcellular events that may
      threaten the viability of rat kidney cells (RKCs) incubated with GNPs irradiated
      with pulsed laser. BACKGROUND DATA: We have previously shown a decrease in the
      viability of RKCs, on incubation with GNPs irradiated with pulsed laser. This
      decrease in viability was concomitant to a reduction in GNP diameter size, and
      reflected the occurrence of subcellular toxic events. METHODS: After incubation
      of RKCs with GNPs irradiated with 532 nm pulsed laser (50 mJ/pulse energy, 5 ns
      duration, and 10 Hz repetition rate for 1, 3, and 5 min), we studied the cell
      membrane integrity, the induction of apoptosis, and the occurrence of oxidative
      stress. We reported the changes induced on RKCs by GNPs irradiated with pulsed
      laser and those induced on the same cells and after the same time intervals by
      unirradiated GNPs; both were related to a negative control. RESULTS: The decrease
      in viability of RKCs on incubation with GNPs irradiated with pulsed laser was
      shown to be mostly secondary to a cell membrane disruption, most probably related
      to the reduction in GNP diameter sizes. The oxidative stress exerted by smaller
      GNPs on RKCs, as well as the induction of apoptosis, seem to be tolerated by the
      RKCs. CONCLUSIONS: Irradiation of GNPs with pulsed laser, to elicit a plasmonic
      photothermal effect, reduces the GNPs' diameter. The smaller-sized GNPs may lead
      to lethal cell membrane disruption in healthy RKCs.

PMID- 24905930
TI  - Application of optical coherence tomography to identify pulp exposure during
      access cavity preparation using an Er:YAG laser.
AB  - OBJECTIVE: The study aimed to evaluate the ability of optical coherence
      tomography (OCT) to guide and identify pulp exposure using an erbium: yttrium
      aluminum-garnet (Er:YAG) laser. BACKGROUND DATA: The Er:YAG laser has been proven
      to be effective in ablating dental hard tissue and offers advantages, as there is
      none of the vibration and noise you get with conventional methods, but it has
      limitations in relation to the tactile feedback that would aid in identification
      of entry into the pulp chamber. Based on depth-resolved optical reflectivity, OCT
      technology has been developed to provide high-resolution, cross-sectional images
      of the internal structure of biological tissues. MATERIALS AND METHODS: The pulp
      chambers of 20 human mandibular incisors were examined, and the average thickness
      of hard tissue covering the pulp chamber was assessed using micro-computed
      tomography (micro-CT) images. An Er:YAG laser was used to gradually penetrate the
      hard tissue over the pulp chamber under microscopic guidance. The preparation was
      constantly imaged using a swept-source OCT at 10 sec intervals until a pulp
      chamber exposure was identified using the technology. The pulp exposure was re
      examined under the microscope and compared with micro-CT images for verification.
      RESULTS: The pulp exposures of 20 incisors were all verified microscopically and
      with micro-CT images. The thickness of hard tissue penetrated by the laser ranged
      from 0.44 to 1.69 mm. CONCLUSIONS: Swept-source OCT is a useful tool for
      identifying pulp exposure during access opening with the Er: YAG laser.

PMID- 24905932
TI  - Diagnostic yield of delayed phase imaging in CT angiography of the head and neck:
      a retrospective study.
AB  - PURPOSE: To evaluate how often delayed images, obtained during neurovascular CTA,
      provide unique information relative to early phase imaging alone. MATERIALS AND
      METHODS: Informed consent was waived by the institutional review body for this
      study. Neurovascular CTAs from January through June 2009 were searched to
      identify those with delayed phase imaging. Reports were reviewed to identify
      cases where delayed images provided potentially unique information. The studies
      with potentially unique information were re-interpreted to determine if the
      information was indeed unique. RESULTS: 645 CTAs with delayed phase imaging were
      identified. There were 324 men and 310 women (median age 67 years; range 20-96
      years). 59 studies (59/645: 9.1%) had findings on the delayed images. There were
      13 cases with hemorrhage, with 4 showing progression on delayed views. Of the
      remaining 46 cases, 28 had occlusion of a vessel that did not reconstitute on the
      delayed images, 6 had occlusion of a vessel that did reconstitute on the delayed
      images, 7 had a string sign which was unchanged on the delayed views and 5 had no
      abnormal findings. Thus in 10 cases the findings were unique to the delayed
      images (10/645: 1.55%). Four showed active bleeding, three showed proximal
      occlusion with distal internal carotid filling from ophthalmic collaterals, two
      showed pial vessels filling distal to proximal MCA occlusion, and one showed
      retrograde vertebral artery filling due to subclavian steal. 95% confidence
      limits of the expected incidence of unique information from the delayed phase
      images are 0.6%-2.5%. CONCLUSION: Obtaining delayed phase imaging for
      neurovascular CTA should be an active decision and not the default protocol. This
      avoids imaging with little, if any value. If delayed images had not been obtained
      in our cohort, no detriment in patient management would have occurred.

PMID- 24905933
TI  - Bioluminescent and micro-computed tomography imaging of bone repair induced by
      fibrin-binding growth factors.
AB  - In this work we have evaluated the capacity of bone morphogenetic protein-2 (BMP
      2) and fibrin-binding platelet-derived growth factor-BB (PDGF-BB) to support cell
      growth and induce bone regeneration using two different imaging technologies to
      improve the understanding of structural and organizational processes
      participating in tissue repair. Human mesenchymal stem cells from adipose tissue
      (hAMSCs) expressing two luciferase genes, one under the control of the
      cytomegalovirus (CMV) promoter and the other under the control of a tissue
      specific promoter (osteocalcin or platelet endothelial cell adhesion molecule),
      were seeded in fibrin matrices containing BMP-2 and fibrin-binding PDGF-BB, and
      further implanted intramuscularly or in a mouse calvarial defect. Then, cell
      growth and bone regeneration were monitored by bioluminescence imaging (BLI) to
      analyze the evolution of target gene expression, indicative of cell
      differentiation towards the osteoblastic and endothelial lineages. Non-invasive
      imaging was supplemented with micro-computed tomography (MUCT) to evaluate bone
      regeneration and high-resolution MUCT of vascular casts. Results from BLI showed
      hAMSC growth during the first week in all cases, followed by a rapid decrease in
      cell number; as well as an increment of osteocalcin but not PECAM-1 expression
      3weeks after implantation. Results from MUCT show that the delivery of BMP-2 and
      PDGF-BB by fibrin induced the formation of more bone and improves
      vascularization, resulting in more abundant and thicker vessels, in comparison
      with controls. Although the inclusion of hAMSCs in the fibrin matrices made no
      significant difference in any of these parameters, there was a significant
      increment in the connectivity of the vascular network in defects treated with
      hAMSCs. 

PMID- 24905934
TI  - Surface engineering of titanium alloy substrates with multilayered biomimetic
      hierarchical films to regulate the growth behaviors of osteoblasts.
AB  - Osseointegration is essential for the long-term survival of orthopedic implants.
      Inspired by the hierarchical structure of natural bone, we fabricated a
      hierarchical structure with osteoinduction potential on titanium alloy (Ti6Al7Nb)
      substrates via a spin-assisted layer-by-layer assembly technique, with
      hydroxyapatite nanofibers as the intercalated materials and gelatin and chitosan
      as the polycation and polyanion, respectively. The as-synthesized hydroxyapatite
      nanofibers were characterized using scanning electron microscopy (SEM),
      transmission electron microscopy, Fourier transform infrared spectroscopy and X
      ray diffraction. The change of water contact angle corresponding to different
      layers indicated the formation of a multilayered structure, since different
      components have their inherent wettability natures. The multilayered lamellar
      structure was revealed by the cross-sectional view of SEM, suggesting that the
      film was successfully deposited onto Ti6Al7Nb substrates. Osteoblasts cultured on
      the hierarchical structure deposited Ti alloy substrates displayed significantly
      higher cell viability (P<0.01) and better adhesion, a higher production level of
      alkaline phosphatase, mineralization, genes expressions of osteocalcin and
      osteopontin (P<0.01 or P<0.05) compared to those of native Ti6Al7Nb substrates
      after culture for 4, 7 or 14days. These results indicated that the lamellar
      structure was beneficial for the biological functions of osteoblasts,
      establishing the basis for osseointegration of a titanium alloy implant. 

PMID- 24905935
TI  - Bone marrow stromal cells on a three-dimensional bioactive fiber mesh undergo
      osteogenic differentiation in the absence of osteogenic media supplements: the
      effect of silanol groups.
AB  - Osteogenic differentiation is a tightly regulated process dependent on the
      stimuli provided by the micro-environment. Silicon-substituted materials are
      known to have an influence on the osteogenic phenotype of undifferentiated and
      bone-derived cells. This study aims to investigate the bioactivity profile as
      well as the mechanical properties of a blend of starch and poly-caprolactone
      (SPCL) polymeric fiber mesh scaffolds functionalized with silanol (Si-OH) groups
      as key features for bone tissue engineering strategies. The scaffolds were made
      from SPCL by a wet spinning technique. A calcium silicate solution was used as a
      non-solvent to develop an in situ functionalization with Si-OH groups in a single
      step approach. We also explored the relevance of silicon incorporated in SPCL-Si
      scaffolds to the in vitro osteogenic process of goat bone marrow stromal cells
      (gBMSCs) with and without osteogenic supplements in the culture medium. We
      hypothesized that SPCL-Si scaffolds could act as physical and chemical millieus
      to induce per se the osteogenic differentiation of gBMSCs. Results show that
      osteogenic differentiation of gBMSCs and the production of a mineralized
      extracellular matrix on bioactive SPCL-Si scaffolds occur for up to 2weeks, even
      in the absence of osteogenic supplements in the culture medium. The omission of
      media supplements to induce osteogenic differentiation is a promising feature
      towards simplified and cost-effective cell culturing procedures of a potential
      bioengineered product, and concomitant translation into the clinical field. Thus,
      the present work demonstrates that SPCL-Si scaffolds and their intrinsic
      properties sustain gBMSC osteogenic features in vitro, even in the absence of
      osteogenic supplements to the culture medium, and show great potential for bone
      regeneration strategies. 

PMID- 24905936
TI  - Degree of cognitive impairment and mortality: a 17-year follow-up in a community
      study.
AB  - BACKGROUND: To test the hypothesis that cognitive impairment in older adults is
      associated with all-cause mortality risk and the risk increases when the degree
      of cognitive impairment augments; and then, if this association is confirmed, to
      report the population-attributable fraction (PAF) of mortality due to cognitive
      impairment. METHOD: A representative random community sample of individuals aged
      over 55 was interviewed, and 4557 subjects remaining alive at the end of the
      first year of follow-up were included in the analysis. Instruments used in the
      assessment included the Mini-Mental Status Examination (MMSE), the History and
      Aetiology Schedule (HAS) and the Geriatric Mental State (GMS)-AGECAT. For the
      standardised degree of cognitive impairment Perneczky et al's MMSE criteria were
      applied. Mortality information was obtained from the official population
      registry. Multivariate Cox proportional hazard models were used to test the
      association between MMSE degrees of cognitive impairment and mortality risk. We
      also estimated the PAF of mortality due to specific MMSE stages. RESULTS:
      Cognitive impairment was associated with mortality risk, the risk increasing in
      parallel with the degree of cognitive impairment (Hazard ratio, HR: 1.18 in the
      'mild' degree of impairment; HR: 1.29 in the 'moderate' degree; and HR: 2.08 in
      the 'severe' degree). The PAF of mortality due to severe cognitive impairment was
      3.49%. CONCLUSIONS: A gradient of increased mortality-risk associated with
      severity of cognitive impairment was observed. The results support the claim that
      routine assessment of cognitive function in older adults should be considered in
      clinical practice.

PMID- 24905937
TI  - Relationship between starch degradation and carbon demand for maintenance and
      growth in Arabidopsis thaliana in different irradiance and temperature regimes.
AB  - Experiments were designed to compare the relationship between starch degradation
      and the use of carbon for maintenance and growth in Arabidopsis in source-limited
      and sink-limited conditions. It is known that starch degradation is regulated by
      the clock in source-limited plants, which degrade their starch in a linear manner
      such that it is almost but not completely exhausted at dawn. We asked whether
      this response is maintained under an extreme carbon deficit. Arabidopsis was
      subjected to a sudden combination of a day of low irradiance, to decrease starch
      at dusk, and a warm night. Starch was degraded in a linear manner through the
      night, even though the plants became acutely carbon starved. We conclude that
      starch degradation is not increased to meet demand in carbon-limited plants. This
      network property will allow stringent control of starch turnover in a fluctuating
      environment. In contrast, in sink-limited plants, which do not completely
      mobilize their starch during the night, starch degradation was accelerated in
      warm nights to meet the increased demand for maintenance and growth. Across all
      conditions, the rate of growth at night depends on the rate of starch
      degradation, whereas the rate of maintenance respiration decreases only when
      starch degradation is very slow. 

PMID- 24905938
TI  - Magnetic compression anastomosis for treatment of benign biliary stricture.
AB  - Endoscopic and percutaneous procedures have shown high success rates when used to
      treat benign biliary stricture. However, cases in which a guidewire cannot be
      passed through a refractory stricture or a complete obstruction are difficult to
      treat using conventional methods. Magnetic compression anastomosis (MCA) has
      emerged as a non-surgical alternative avoiding operational mortality and
      morbidity. The feasibility and safety of MCA have been experimentally and
      clinically verified in cases of biliobiliary and bilioenteric anastomosis.
      However, no pre-MCA assessment modality capable of predicting outcomes is as yet
      available, and no universally effective magnet delivery method has as yet been
      established, rendering it difficult to identify patients for whom MCA is
      appropriate. Various experimental studies seeking to overcome these limitations
      are underway. Such work will improve our in-depth understanding of MCA, which has
      been trialed in various fields. Upon further development, MCA may become a ground
      breaking option for treatment of benign strictures that are difficult to resolve
      using conventional methods, and MCA may be expected to be minimally traumatic and
      highly effective. The aim of the present study was to discuss the current status
      of MCA and the direction of MCA development by reviewing clinical and
      experimental MCA data. 

PMID- 24905939
TI  - Intracellular MMP-2 activity in skeletal muscle is associated with type II
      fibers.
AB  - Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme implicated in
      motility, differentiation, and regeneration of skeletal muscle fibers through
      processing of extracellular substrates. Although MMP-2 has been found to be
      localized intracellularly in cardiomyocytes where the enzyme is thought to
      contribute to post-ischemic loss of contractility, little is known about
      intracellular MMP-2 activity in skeletal muscle fibers. In the present study we
      demonstrate intracellular MMP-2 in normal skeletal muscle by immunohistochemical
      staining. Immunogold electron microscopic analyses indicated that the enzyme was
      concentrated in Z-lines of the sarcomers, in the nuclear membrane, and in
      mitochondria. By use of in situ zymography, we found that gelatinolytic activity
      in muscle fibers was co-localized with immunofluorecent staining for MMP-2.
      Staining for MMP-9, the other member of the gelatinase group of the MMPs, was
      negative. The broad-spectrum metalloprotease inhibitor EDTA and the selective
      gelatinase inhibitor CTT2, but not the cysteine inhibitor E64, strongly reduced
      the gelatinolytic activity. The intracellular gelatinolytic activity was much
      more prominent in fast twitch type II fibers than in slow twitch type I fibers,
      and there was a decrease in intracellular gelatinolytic activity and MMP-2
      expression in muscles from mice exposed to high intensity interval training.
      Together our results indicate that MMP-2 is part of the intracellular proteolytic
      network in normal skeletal muscle, especially in fast twitch type II fibers.
      Further, the results suggest that intracellular MMP-2 in skeletal muscle fibers
      is active during normal homeostasis, and affected by the level of physical
      activity.

PMID- 24905940
TI  - Involvement of CaM-CaMKII-ERK in bisphenol A-induced Sertoli cell apoptosis.
AB  - Bisphenol A (BPA), one of the most prevalent chemicals for daily use, has been
      reported as a xenoestrogen to induce reproductive toxicity, but its mechanism is
      poorly understood. In the present study, we aimed to explore whether CaM-CaMKII
      ERK1/2 signaling pathway was involved in BPA-induced Sertoli cells injury via the
      mitochondrial apoptotic pathway. TM4 cells were cultured with 0, 0.02, 0.2, 2.0,
      20MUM BPA, and cell viability, mitochondrial function and CaM-CaMKII-ERK1/2
      signal pathway were examined. With the MTT assay, BPA was found to suppress cell
      viability in a dose- and time-dependent manner. Moreover, mitochondrial mass
      loss, membrane potential decrease, cytochrome c release, Bcl-2 family members
      down-regulation and caspases-3 up-regulation were obviously observed when the TM4
      cells were exposed to BPA. Additionally, the expression of calmodulin (CaM) and
      phosphorylation of calcium/calmodulin dependent kinase II (CaMKII) significantly
      increased, and pretreatment with 10MUM antagonist of CaM (W-7) or CaMKII (KN62)
      prevented cell damage through mitochondrial apoptotic pathway. In parallel,
      ERK1/2 pathway was proved to participate in BPA-induced cell damage, since W-7
      and KN62 partially suppressed ERK1/2 activation, and PD98059, the ERK1/2
      antagonist, significantly attenuated BPA-induced cell damage. These data, taken
      together, indicated that CaM-CaMKII-ERK axis might transmit apoptotic signals to
      the mitochondria during BPA-induced cell apoptosis. By exploring the mechanisms
      of the Ca(2+) homeostasis and the corresponding proteins, our study provides new
      insight into BPA-induced reproductive toxicity. 

PMID- 24905941
TI  - Matrix models for size-structured populations: unrealistic fast growth or simply
      diffusion?
AB  - Matrix population models are widely used to study population dynamics but have
      been criticized because their outputs are sensitive to the dimension of the
      matrix (or, equivalently, to the class width). This sensitivity is concerning for
      the population growth rate (lambda) because this is an intrinsic characteristic
      of the population that should not depend on the model specification. It has been
      suggested that the sensitivity of lambda to matrix dimension was linked to the
      existence of fast pathways (i.e. the fraction of individuals that systematically
      move up a class), whose proportion increases when class width increases. We
      showed that for matrix population models with growth transition only from class i
      to class i + 1, lambda was independent of the class width when the mortality and
      the recruitment rates were constant, irrespective of the growth rate. We also
      showed that if there were indeed fast pathways, there were also in about the same
      proportion slow pathways (i.e. the fraction of individuals that systematically
      remained in the same class), and that they jointly act as a diffusion process
      (where diffusion here is the movement in size of an individual whose size
      increments are random according to a normal distribution with mean zero). For 53
      tree species from a tropical rain forest in the Central African Republic, the
      diffusion resulting from common matrix dimensions was much stronger than would be
      realistic. Yet, the sensitivity of lambda to matrix dimension for a class width
      in the range 1-10 cm was small, much smaller than the sampling uncertainty on the
      value of lambda. Moreover, lambda could either increase or decrease when class
      width increased depending on the species. Overall, even if the class width should
      be kept small enough to limit diffusion, it had little impact on the estimate of
      lambda for tree species.

PMID- 24905942
TI  - Continuous high-pressure negative suction drain: new powerful tool for closed
      wound management: clinical experience.
AB  - BACKGROUND: Although various reconstructive flap surgeries have been successfully
      performed, there still are difficult wound complications, such as seroma
      formation, wound margin necrosis, delayed wound healing, and even flap failures.
      The negative-pressure wound therapy has been described in detail in the
      literature to assist open chronic/complex wound closure in reconstructive
      surgery. However, the negative-pressure wound therapy was difficult to be applied
      under the incisional closed wounds. METHODS: A total of 23 patients underwent the
      various reconstructive flap surgeries with continuous high-pressure negative
      suction drain. Instead of using regular suction units, Barovac (50-90 mm Hg,
      Sewoon Medical, Seoul, Republic of Korea) drainage tubes were connected to the
      wall suction unit, providing continuous high-powered negative pressure. In
      addition, continuous subatmospheric suction pressure (100-300 mm Hg) was applied.
      Outcome of the measures was obtained from the incidence of seroma, volume of
      postoperative drainage, hospitalization period, and incidence of other typical
      wound complications. Dead space was evaluated postoperatively with
      ultrasonography. RESULTS: Using continuous high-pressure negative suction drain,
      successful management of seroma was obtained without any major complication such
      as wound infection, flap loss, and wound margin necrosis, except for only 1 case
      of seroma after discharge from the hospital. The indwelling time of the drain in
      the latissimus dorsi donor site was significantly reduced in comparison with the
      authors' previous data (P = 0.047). The volume of drainage and hospitalization
      period were also reduced; however, these were not statistically significant. The
      dead space with continuous high-pressure negative suction drain was more reduced
      than in the control group in the immediate postoperative period and confirmed
      with ultrasonography. CONCLUSIONS: Continuous high-pressure negative suction
      drain might be the simple and powerful solution in the management of challenging
      closed wounds.

PMID- 24905943
TI  - Evaluation of bone graft harvesting techniques from anterior ilium.
AB  - Autogenous bone harvest from the anterior ilium is a common procedure in the
      surgical field. In the current study, a retrospective analysis was performed
      regarding the bone graft harvesting techniques from the anterior ilium. The
      retrospective analysis with a 1-year period included 16 patients who had
      undergone iliac bone grafting for oral and maxillofacial reconstruction. Medial
      and lateral approaches were assessed. No major complications were observed. One
      patient undergoing medial approach and 2 patients undergoing lateral approach
      experienced gait disturbances at the postoperative period. Harvesting bone from
      the anterior ilium did not result in greater donor site morbidity or
      complications in the early term. The medial approach revealed an earlier recovery
      time than the lateral one. Anterior ilium is a good choice for the reconstruction
      of jaws, but donor site morbidity remains a problem and should be considered in
      the treatment plan. 

PMID- 24905944
TI  - Evaluation of the protective effect of alpha-lipoic acid on cisplatin ototoxicity
      using distortion-product otoacoustic emission measurements: an experimental
      animal study.
AB  - The aim of our study was to determine the effectiveness of intratympanic alpha
      lipoic acid injection as an otoprotective agent against cisplatin-induced
      ototoxicity in guinea pigs. Twenty-four adult male albino guinea pigs with normal
      hearing were divided into 4 groups. The guinea pigs received intraperitoneal
      cisplatin in group 1, intraperitoneal cisplatin and intratympanic alpha-lipoic
      acid in group 2, intratympanic alpha-lipoic acid in group 3, as well as
      intraperitoneal cisplatin and intratympanic saline in group 4. Distortion-product
      otoacoustic emission measurements were obtained for both ears at the following
      time points: before administration (baseline recording) and on day 3 (72 h
      later). In group 1 (cisplatin), significant deterioration was observed at all
      frequencies on day 3 (P < 0.05). In group 2 (cisplatin + alpha-lipoic acid),
      deterioration was observed at all frequencies on day 3; however, this
      deterioration did not reach a statistical significance (P > 0.05). In group 3
      (alpha-lipoic acid), no significant difference was observed between baseline and
      day 3 (P > 0.05). In group 4 (cisplatin + saline), deterioration was observed at
      all frequencies on day 3; however, this deterioration did not reach a statistical
      significance (P > 0.05). Cisplatin-induced hearing loss in the guinea pigs may be
      limited to some extent by the concomitant use of alpha-lipoic acid. Dose
      dependent changes in the possible effects of alpha-lipoic acid need further
      investigation. Future morphologic studies may contribute to expose clearly the
      protective effect of alpha-lipoic acid. 

PMID- 24905945
TI  - Intramuscular cavernous hemangioma of the temporalis muscle.
AB  - Hemangiomas are frequent benign hereditary vascular tumors. Intramuscular
      hemangiomas, a distinctive type of hemangioma occurring within the skeletal
      muscle, account for less than 1% of all hemangiomas. They occur more often in the
      trunk and extremity muscles, whereas the involvement of the temporal muscle is
      extremely rare. A 34-year-old man with a mass in his left temporal fossa was
      admitted. Computed tomographic scan showed no erosion of the bone, and magnetic
      resonance imaging revealed an ovoid mass within the temporal muscle. The lesion
      was surgically excised, and histopathologic examination confirmed the diagnosis
      of cavernous hemangioma. The patient was not able to lift his left eyebrow right
      after the surgery. Two months after the surgery, the patient recovered from
      paralysis, and there was no recurrence of tumor 12 months after the surgery. We
      report the 27th cavernous hemangioma case of the temporalis muscle. Care must be
      taken to avoid possible stretch injury to facial nerve branches while resecting
      these tumors. 

PMID- 24905946
TI  - Dysphagia and airway obstruction due to large cervical osteophyte in a patient
      with ankylosing spondylitis.
AB  - Anterior cervical osteophytes are excessive bony formation of cervical vertebra
      bodies. They are common but rarely symptomatic lesions mostly seen in geriatric
      population. Large anterior cervical osteophytes may cause symptoms such as
      dysphagia, dyspnea, dysphonia, and odynophagia. They have been attributed to
      multiple etiologies including diffuse idiopathic skeletal hyperostosis, following
      trauma, cervical spondylitis, and infectious spondylitis. However, symptomatic
      large anterior cervical osteophyte with ankylosing spondylitis is extremely rare.
      Surgical excision is the main treatment for symptomatic cases. We report a case
      of a 53-year-old man with airway obstruction and dysphagia due to large cervical
      osteophyte who has a history of ankylosing spondylitis, and we also addressed the
      etiological factors and management of large symptomatic cervical osteophytes. 

PMID- 24905947
TI  - Closed reduction and percutaneous Kirschner wire fixation in the treatment of
      simple zygoma fractures: orbital volumetric outcomes.
AB  - INTRODUCTION: The primary goal of treatment of fractures of the zygoma is the
      perfect restoration of function and aesthetic appearance. An adequate surgical
      treatment must combine adequate fracture reduction with the lowest possible
      morbidity of the surrounding soft tissues. This is the principle that guides the
      use of closed method for the treatment of simple fractures of the zygomatic bone.
      For a long-term evaluation, it is necessary to develop a method of volumetric
      orbitometry using tomography and use it for the evaluation of recent and late
      outcomes of patients treated with the closed technique. METHODS: We present a
      study consisting of 3 consecutive phases that aimed to evaluate the orbital
      volume in late postoperative patients with simple fractures of the zygomatic bone
      treated with closed reduction. In the first phase, examinations of 21 patients
      were selected and a method was developed for volumetric orbitometry. This method
      was tested by 3 averiguadores (certified radiologists). After defining the
      volumetric method, the second stage was started, when 10 examinations of the
      patients who had been diagnosed with simple fractures of the zygomatic bone were
      selected. These examinations were from the patients who underwent conservative
      treatment and who also had a computed tomographic scan in a maximum period of 7
      days postoperatively. In the third phase of the study, we selected 10 other
      examinations of the patients who had been operated on with the closed method in
      over 12 months. Orbital volumetry analysis of late results was performed.
      RESULTS: In the first phase, the method for orbital volumetry by helical computed
      tomographic scan showed adequate precision and accuracy. Furthermore, it was able
      to set the possibility of using an orbit control volume at each other. In the
      second phase, the statistical analysis of the mean orbital volumetry showed that
      zygomatic fractures alter the orbital volume and that the closed technique is
      able to restore these volumes. In the third phase, the volumetry of the orbits of
      the patients with late follow-up of unilateral closed reduction of fractures of
      the zygoma also showed the maintenance of the results. CONCLUSIONS: The current
      study was able to develop a reliable method of volumetry and use it to the
      evaluation of patients in recent and late postoperative period who were treated
      with closed technique.

PMID- 24905948
TI  - Endoscope-assisted conservative condylectomy combined with orthognathic surgery
      in the treatment of mandibular condylar osteochondroma.
AB  - Mandibular condylar osteochondroma (OC) results in asymmetric prognathism with
      facial morphologic and functional disturbance. The aim of this study was to
      explore the feasibility of endoscope-assisted conservative condylectomy combined
      with simultaneous orthognathic surgery in the treatment of condylar OC. Thirteen
      patients with OC of the mandibular condyle were enrolled in this study. With the
      aid of endoscope, condylar OC resection and conservative condylectomy were
      carried out via intraoral approach. A direct vision of the magnified and
      illuminated operative field was realized. Simultaneous orthognathic surgery was
      used to correct facial asymmetry and malocclusion. All patients healed
      uneventfully. No facial nerve injury and salivary fistula occurred. Facial
      symmetry and morphology were greatly improved, and stable occlusion was obtained
      in all cases. The patients showed no signs of recurrence and temporomandibular
      joint ankylosis in the 16 to 54 months of follow-up. Endoscope-assisted tumor
      resection and condylectomy combined with simultaneous orthognathic surgery
      provide us a valuable option in the treatment of mandibular condylar OC. 

PMID- 24905949
TI  - Emergence of metallicity in silver clusters in the 150 atom regime: a study of
      differently sized silver clusters.
AB  - We report the systematic appearance of a plasmon-like optical absorption feature
      in silver clusters protected with 2-phenylethanethiol (PET), 4-flurothiophenol (4
      FTP) and (4-(t-butyl)benzenethiol (BBS) as a function of cluster size. A wide
      range of clusters, namely, Ag44(4-FTP)30, Ag55(PET)31, ~Ag75(PET)40,
      ~Ag114(PET)46, Ag152(PET)60, ~Ag202(BBS)70, ~Ag423(PET)105, and ~Ag530(PET)100
      were prepared. The UV/Vis spectra show multiple features up to ~Ag114; and
      thereafter, from Ag152 onwards, the plasmonic feature corresponding to a single
      peak at ~460 nm evolves, which points to the emergence of metallicity in clusters
      composed of ~150 metal atoms. A minor blue shift in the plasmonic peak was
      observed as cluster sizes increased and merged with the spectrum of plasmonic
      nanoparticles of 4.8 nm diameter protected with PET. Clusters with different
      ligands, such as 4-FTP and BBS, also show this behavior, which suggests that the
      'emergence of metallicity' is independent of the functionality of the thiol
      ligand.

PMID- 24905950
TI  - Electrospun P2-type Na(2/3)(Fe(1/2)Mn(1/2))O2 hierarchical nanofibers as cathode
      material for sodium-ion batteries.
AB  - Sodium-ion batteries can be the best alternative to lithium-ion batteries,
      because of their similar electrochemistry, nontoxicity, and elemental abundance
      and the low cost of sodium. They still stand in need of better cathodes in terms
      of their structural and electrochemical aspects. Accordingly, the present study
      reports the first example of the preparation of Na2/3(Fe1/2Mn1/2)O2 hierarchical
      nanofibers by electrospinning. The nanofibers with aggregated nanocrystallites
      along the fiber direction have been characterized structurally and
      electrochemically, resulting in enhanced cyclability when compared to
      nanoparticles, with initial discharge capacity of ~195 mAh g(-1). This is
      attributed to the good interconnection among the fibers, with well-guided charge
      transfers and better electrolyte contacts. 

PMID- 24905951
TI  - Acronyms Confuse Everyone: combating the use of acronyms to describe paediatric
      research studies.

PMID- 24905952
TI  - Oral potentially malignant disorders: is malignant transformation predictable and
      preventable?
AB  - Leukoplakia is the most common potentially malignant disorder of the oral mucosa.
      The prevalence is approximately 1% while the annual malignant transformation
      ranges from 2% to 3%. At present, there are no reliable clinicopathological or
      molecular predicting factors of malignant transformation that can be used in an
      individual patient and such event can not truly be prevented. Furthermore, follow
      up programs are of questionable value in this respect. Cessation of smoking
      habits may result in regression or even disappearance of the leukoplakia and will
      diminish the risk of cancer development either at the site of the leukoplakia or
      elsewhere in the mouth or the upper aerodigestive tract. The debate on the
      allegedly potentially malignant character of oral lichen planus is going on
      already for several decades. At present, there is a tendency to accept its
      potentially malignant behaviour, the annual malignant transformation rate
      amounting less than 0.5%. As in leukoplakia, there are no reliable predicting
      factors of malignant transformation that can be used in an individual patient and
      such event can not truly be prevented either. Follow-up visits, e.g twice a year,
      may be of some value. It is probably beyond the scope of most dentists to manage
      patients with these lesions in their own office. Timely referral to a specialist
      seems most appropriate, indeed. 

PMID- 24905953
TI  - A UV-Vis photoacoustic spectrophotometer.
AB  - A novel photoacoustic spectrophotometer (PAS) for the measurement of gas-phase
      and aerosol absorption over the UV-visible region of the spectrum is described.
      Light from a broadband Hg arc lamp is filtered in eight separate bands from 300
      to 700 nm using bandpass interference filters (centered at 301 nm, 314 nm, 364
      nm, 405 nm, 436 nm, 546 nm, 578 and 687 nm) and modulated with an optical chopper
      before entering the photoacoustic cell. All wavelength bands feature a 20-s
      detection limit of better than 3.0 Mm(-1) with the exception of the lower
      intensity 687 nm band for which it is 10.2 Mm(-1). Validation measurements of gas
      phase acetone and nigrosin aerosol absorption cross sections at several
      wavelengths demonstrate agreement to within 10% with those measured previously
      (for acetone) and those predicted by Mie theory (for nigrosin). The PAS
      instrument is used to measure the UV-visible absorption spectrum of ambient
      aerosol demonstrating a dramatic increase in the UV region with absorption
      increasing by 300% from 405 to 301 nm. This type of measurement throughout the UV
      visible region and free from artifacts associated with filter-based methods has
      not been possible previously, and we demonstrate its promise for classifying and
      quantifying different types of light-absorbing ambient particles. 

PMID- 24905954
TI  - Cobalt-catalyzed addition of arylzinc reagents to norbornene derivatives through
      1,4-cobalt migration.
AB  - A cobalt-diphosphine catalyst promotes the addition of an arylzinc reagent to a
      norbornene derivative to afford o-(2-exo-norbornyl)arylzinc species. This
      "migratory arylzincation" reaction is considered to involve insertion of
      norbornene into an arylcobalt species, alkyl-to-aryl 1,4-cobalt migration, and
      transmetalation between the resulting o-(2-exo-norbornyl)arylcobalt species and
      the arylzinc reagent. The o-(2-exo-norbornyl)arylzinc species can be intercepted
      by common organic electrophiles under copper or palladium catalysis. 

PMID- 24905955
TI  - Utility of intracerebral theta burst electrical stimulation to attenuate
      interhemispheric inhibition and to promote motor recovery after cortical injury
      in an animal model.
AB  - Following a cerebral cortex injury such as stroke, excessive inhibition around
      the core of the injury is thought to reduce the potential for new motor learning.
      In part, this may be caused by an imbalance of interhemispheric inhibition (IHI);
      therefore, treatments that relieve the inhibitory drive from the healthy
      hemisphere to the peri-lesional area may enhance motor recovery. Theta burst
      stimulation delivered by transcranial magnetic stimulation has been tested as a
      means of normalizing IHI, but clinical results have been variable. Here we use a
      new rat model of synaptic IHI to demonstrate that electrical intracranial theta
      burst stimulation causes long-lasting changes in motor cortex excitability.
      Further, we show that contralateral intermittent theta burst stimulation (iTBS)
      blocks IHI via a mechanism involving cannabinoid receptors. Finally, we show that
      contralesional iTBS applied during recovery from cortical injury in rats improves
      the recovery of motor function. These findings suggest that theta burst
      stimulation delivered through implanted electrodes may be a promising avenue to
      explore for augmenting rehabilitation from brain injury. 

PMID- 24905956
TI  - Dendritic cell subsets involved in type I IFN induction in mouse measles virus
      infection models.
AB  - Measles caused by measles virus (MV) infection remains important in child
      mortality. Although the natural host of MV is human, mouse models expressing MV
      entry receptors (human CD46, CD150) and disrupting the interferon (IFN) pathways
      work for investigating immune responses during early MV infection in vivo.
      Dendritic cells (DCs) are primary targets for MV in the mouse models and are
      efficiently infected with several MV strains in the respiratory tract in vivo.
      However, questions remain about what kind of DC in a variety of DC subsets is
      involved in initial MV infection and how the RNA sensors evoke circumventing
      signals against MV in infected DCs. Since type I IFN-inducing pathways are a
      pivotal defense system that leads to the restriction of systemic viral infection,
      we have generated CD150-transgenic mice with disrupting each of the IFN-inducing
      pathway, and clarified that DC subsets had subset-specific IFN-inducing systems,
      which critically determined the DC's differential susceptibility to MV. 

PMID- 24905957
TI  - Signalling pathways involved in antitumoral effects of VIP in human renal cell
      carcinoma A498 cells: VIP induction of p53 expression.
AB  - Vasoactive intestinal peptide (VIP) decreases cell proliferation through PI3K
      signalling and prevents tumour progression in clear renal cell carcinoma (RCC).
      Here we analyzed the signalling pathways that mediate such VIP effects by using
      human RCC A498 cells. The effects of treatment with 1 MUM VIP and/or specific
      protein kinase inhibitors such as H89, Wortmannin and PD98059 were studied by
      cell adhesion assay, ELISA of VEGF165 and ROS production assays. Semiquantitative
      RT-PCR and western blot were performed to study p53 expression. VIP increased
      cell adhesion and ROS production, and decreased VEGF165 secretion through PI3K
      signalling. Moreover, VIP increased nuclear expression of tumour suppressor p53.
      VIP effects could be blocked by cell incubation with a specific p53 inhibitor,
      cyclin pifithrin-alpha hydrobromide (CPFT-alphaH). In conclusion, this study
      provides a p53-dependent mechanism by which VIP regulates cell proliferation in
      RCC development. It supports a potential usefulness of VIP in new therapies of
      RCC.

PMID- 24905958
TI  - Predictors and outcome of pain-related avoidance of activities in persons with
      early symptomatic knee osteoarthritis: a five-year followup study.
AB  - OBJECTIVE: It has been hypothesized that pain and low vitality lead to an
      increase in avoidance of activities in persons with early symptomatic knee
      osteoarthritis (OA), and that avoidance of activities leads to an increase in
      activity limitations. The present study aimed to evaluate these hypotheses.
      METHODS: Baseline, 2-year, and 5-year followup data of 828 participants from the
      Cohort Hip and Cohort Knee Study with early symptomatic knee OA were used.
      Autoregressive generalized estimating equations and linear regression models were
      used to analyze the longitudinal and cross-sectional associations between self
      reported knee pain, vitality, pain-related avoidance of activities, and activity
      limitations. The models were adjusted for the covariates age, sex, education
      level, body mass index, comorbidity, radiographic severity, and hip pain.
      RESULTS: In longitudinal analyses, knee pain and vitality predicted a subsequent
      increase in avoidance of activities. Pain-related avoidance of activities
      predicted a subsequent increase in activity limitations; however, this
      relationship lost statistical significance (P = 0.089) after adjustment for
      covariates. Cross-sectional analyses showed strong relationships between knee
      pain, low vitality, pain-related avoidance of activities, and activity
      limitations at all time points. CONCLUSIONS: In persons with early symptomatic
      knee OA, knee pain and low vitality lead to a subsequent increase in avoidance of
      activities. Pain-related avoidance of activities is related to activity
      limitations at inception of symptoms, but also years later. Therefore, it can be
      recommended to monitor and target avoidance of activities at various stages of
      the disease.

PMID- 24905959
TI  - Polyphenols from blueberries modulate inflammation cytokines in LPS-induced
      RAW264.7 macrophages.
AB  - Polyphenols including 3-glucoside/arabinoside/galactoside-based polymers of
      delphinidins, petunidins, peonidins, malvidins and cyanidins are one type of
      biological macromolecules, which are extraordinarily rich in blueberries. Anti
      inflammatory activity of blueberry polyphenols (BPPs) was investigated by using
      lipopolysaccharide (LPS) induced RAW264.7 macrophages. The results showed that
      BPPs suppressed the gene expression of IL-1beta (interleukin-1beta), IL-6 and IL
      12p35. The inhibition effect on IL-1beta and IL-6 mRNA was most obvious at the
      concentration of 10-200MUg/mL BPPs. But the inhibition effect on IL-12p35 mRNA
      was increased with the increasing concentration of BPPs. When fixed at 100MUg/mL
      BPPs, the most significant inhibition on IL-1beta, IL-6 and IL-12p35 mRNA
      expression was detected at 12-48h. In conclusion, BPPs exhibit anti-inflammation
      activity by mediating and modulating the balances in pro-inflammatory cytokines
      of IL-1beta, IL-6, and IL-12. 

PMID- 24905960
TI  - Synthesis of stereoregular polymers through ring-opening metathesis
      polymerization.
AB  - Some of the most readily available and inexpensive monomers for ring-opening
      metathesis polymerization (ROMP) are norbornenes or substituted norbornadienes.
      Polymers made from them have tacticities (the stereochemical relationship between
      monomer units in the polymer chain) that remain after the C?C bonds in the
      polymer backbone are hydrogenated. Formation of polymers with exclusively a
      single structure (one tacticity) was rare until approximately 20 years ago, when
      well-defined ROMP catalysts based on molybdenum imido alkylidene complexes that
      contain a chiral biphenolate or binaphtholate ligand were shown to yield
      cis,isotactic-poly(2,3-dicarbomethoxynorbornadiene) and related polymers through
      addition of the monomer to the same side of the M?C bond in each step. Over the
      past few years, molybdenum and tungsten monoaryloxide pyrrolide (MAP) imido
      alkylidene initiators have been found to produce cis,syndiotactic polynorbornenes
      and substituted norbornadienes through addition of the monomer to one side of the
      M?C bond in one step followed by addition to the other side of the M?C bond in
      the next step. This "stereogenic metal control" is possible as a consequence of
      the fact that the configuration of the stereogenic metal center switches with
      each step in the polymerization. Stereogenic metal control also allows
      syndiotactic polymers to be prepared from racemic monomers in which enantiomers
      of the monomer are incorporated alternately into the main chain. Because pure
      trans polymers have not yet been prepared through some predictable mechanism of
      stereochemical control, it seems unlikely that all four basic polymer structures
      from a single given monomer can be prepared simply by choosing the right
      initiator. However, because tactic, and relatively oxygen-stable, hydrogenated
      polymers are often a desirable goal, the ability to form pure cis,isotactic
      polymers (through enantiomorphic site control) and cis,syndiotactic polymers
      (through stereogenic metal control) is sufficient for preparing hydrogenated
      polymers with a single structure. It is hoped that the principles of forming
      polymers that have a single structure through ring-opening metathesis
      polymerization will be general for a relatively large number of monomers and that
      some important problems in ROMP polymer chemistry can benefit from knowledge of
      polymer structure at a molecular level. With an increase in knowledge concerning
      the mechanistic details of polymerization by well-defined initiators, more
      elaborate ROMP polymers and copolymers with stereoregular structures may be
      possible.

PMID- 24905961
TI  - Proximity to traffic, ambient air pollution, and community noise in relation to
      incident rheumatoid arthritis.
AB  - BACKGROUND: The risk of rheumatoid arthritis (RA) has been associated with living
      near traffic; however, there is evidence suggesting that air pollution may not be
      responsible for this association. Noise, another traffic-generated exposure, has
      not been studied as a risk factor for RA. OBJECTIVES: We investigated proximity
      to traffic, ambient air pollution, and community noise in relation to RA in the
      Vancouver and Victoria regions of British Columbia, Canada. METHODS: Cases and
      controls were identified in a cohort of adults that was assembled using health
      insurance registration records. Incident RA cases from 1999 through 2002 were
      identified by diagnostic codes in combination with prescriptions and type of
      physician (e.g., rheumatologist). Controls were matched to RA cases by age and
      sex. Environmental exposures were assigned to each member of the study population
      by their residential postal code(s). We estimated relative risks using
      conditional logistic regression, with additional adjustment for median income at
      the postal code. RESULTS: RA incidence was increased with proximity to traffic,
      with an odds ratio (OR) of 1.37 (95% CI: 1.11, 1.68) for residence <= 50 m from a
      highway compared with residence > 150 m away. We found no association with
      traffic-related exposures such as PM2.5, nitrogen oxides, or noise. Ground-level
      ozone, which was highest in suburban areas, was associated with an increased risk
      of RA (OR = 1.26; 95% CI: 1.18, 1.36 per interquartile range increase).
      CONCLUSIONS: Our study confirms a previously observed association of RA risk with
      proximity to traffic and suggests that neither noise levels nor traffic-related
      air pollutants are responsible for this relationship. Additional investigation of
      neighborhood and individual correlates of residence near roadways may provide new
      insight into risk factors for RA.

PMID- 24905962
TI  - Gender difference in the association of hyperuricemia with hypertension in a
      middle-aged Chinese population.
AB  - In this study, we report the relationship between hyperuricemia and hypertension
      in a middle-aged Chinese population, emphasizing the difference of gender. The
      cross-sectional study was conducted among 1776 adults aged 45-60 years, who
      participated in the Hefei Nutrition and Health Study (2012). Hyperuricemia was
      defined as serum uric acid (SUA)> 420 MUmol/l for men, and > 360 MUmol/l for
      women. Hypertension was defined as systolic blood pressure (SBP) >= 140 mmHg or
      diastolic blood pressure (DBP) >= 90 mmHg. Anthropometric measurements and
      biochemical data were collected using standardized procedures. Multivariate
      logistic regression analysis was performed to determine the relationship between
      hyperuricemia and hypertension with adjustment of potential confounding factors.
      Body mass index (BMI), waist circumference (WC), SBP, DBP, fasting glucose, SUA
      and the prevalence of hyperuricemia and hypertension were significantly higher in
      male than in female (p < 0.001). Females had significantly higher levels of
      triglycerides (TG) and high-density lipoprotein (HDL)-cholesterol (5.23 +/- 0.87
      vs 5.12 +/- 1.01, p < 0.05, 1.50 +/- 0.37 vs 1.28 +/- 0.41, respectively.) than
      males. Simple correlation analysis showed that SUA was positively associated with
      WC and TG. In addition, after adjusting for potential confounders, hyperuricemia
      was associated with increased risk of hypertension in both males and females,
      with odds ratios (95% CI) of 1.680 (1.110-2.543) and 1.065 (1.012-1.118),
      respectively. Conclusions: The association of hyperuricemia with hypertension was
      stronger in males than in females, and middle-aged men with hyperuricemia had
      greater association with hypertension. Our findings remain to be confirmed in
      future prospective studies.

PMID- 24905963
TI  - Comparative studies of zebrafish Danio rerio lipoprotein lipase (lpl) and hepatic
      lipase (lipc) genes belonging to the lipase gene family: evolution and expression
      pattern.
AB  - In this study, bioinformatics analysis, tissue distribution and developmental
      expression pattern of lipoprotein lipase (lpl) and hepatic lipase (lipc) in
      zebrafish Danio rerio are reported. In adult D. rerio, lpl was highly expressed
      in liver. This is remarkably different from the tissue expression pattern of LPL
      in mammals, which is not detected in the adult liver. The expression of lipc was
      liver specific, which is consistent with that in mammals. During embryogenesis,
      lpl mRNA was increased gradually in concentration from 0.5 hpf (hour post
      fertilization) to 6 dpf (days post fertilization), but lipc was not expressed at
      the early stage of the embryo until 3 dpf. In situ hybridization further
      displayed the expression pattern of lpl mainly restricted to the head region
      including cells surrounding the mouth opening, branchial arches, pectoral fin and
      lateral line neuromast, whereas lipc was mainly restricted to the liver and part
      of head regions including lens. This lays a foundation for further investigation
      of lpl or lipc function and evolution in fishes.

PMID- 24905964
TI  - Transposition of the great arteries and sinus venosus defect with partially
      anomalous pulmonary venous return: physiological and anatomic considerations.
AB  - Transposition of the great arteries is a common congenital heart defect causing
      cyanosis in neonates, occurring in 0.2 per 1000 live births. It has been reported
      to occur with other associated congenital heart lesions. However, its association
      with a superior sinus venosus defect and partially anomalous pulmonary venous
      return has not been reported. We present a neonate with transposition of the
      great arteries, superior sinus venosus defect with partially anomalous pulmonary
      venous return that underwent successful complete neonatal repair, and discuss
      important physiological and anatomic considerations. 

PMID- 24905965
TI  - Ipsilateral renal function preservation after robot-assisted partial nephrectomy
      (RAPN): an objective analysis using mercapto-acetyltriglycine (MAG3) renal scan
      data and volumetric assessment.
AB  - OBJECTIVE: To objectively assess ipsilateral renal function (IRF) preservation
      and factors influencing it after robot-assisted partial nephrectomy (RAPN).
      PATIENTS AND METHODS: Our database was queried to identify patients who had
      undergone RAPN from 2007 to 2013 and had complete pre- and postoperative mercapto
      acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular
      filtration rate (eGFR) for the operated kidney was calculated by multiplying the
      percentage of contribution from the renal scan by the total eGFR. IRF
      preservation was defined as a ratio of the postoperative eGFR for the operated
      kidney to the preoperative eGFR for the operated kidney. The percentage of total
      eGFR preservation was calculated in the same manner (postoperative
      eGFR/preoperative eGFR * 100). The amount of healthy rim of renal parenchyma
      removed was assessed by deducting the volume of tumour from the volume of the PN
      specimen assessed on pathology. Multivariable linear regression was used for
      analysis. RESULTS: In all, 99 patients were included in the analysis. The overall
      median (interquartile range) total eGFR preservation and IRF preservation for the
      operated kidney was 83.83 (75.2-94.1)% and 72 (60.3-81)%, respectively (P <
      0.01). On multivariable analysis, volume of healthy rim of renal parenchyma
      removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated
      kidney preoperative eGFR were predictive of IRF preservation. CONCLUSIONS: Using
      total eGFR tends to overestimate the degree of renal function preservation after
      RAPN. This is particularly relevant when studying factors affecting functional
      outcomes after nephron-sparing surgery. IRF may be a more precise assessment
      method in this setting. Operated kidney baseline renal function, BMI, WIT >30
      min, and amount of resected healthy renal parenchyma represent the factors with a
      significant impact on the IRF preservation. RAPN provides significant
      preservation of renal function as shown by objective assessment criteria.

PMID- 24905966
TI  - IRMPD spectroscopy of metalated flavins: structure and bonding of M(q+)
      lumichrome complexes (M(q+) = Li+-Cs+, Ag+, Mg2+).
AB  - Infrared multiphoton dissociation (IRMPD) spectra of mass selected isolated metal
      lumichrome ionic complexes, M(q+)LCn with M(q+) = Li(+), Na(+), K(+), Rb(+),
      Cs(+), Ag(+) (n = 1), and Mg(2+) (n = 2), are recorded in the fingerprint range.
      The complexes are generated in an electrospray ionization source coupled to an
      ion cyclotron mass spectrometer and the IR free electron laser FELIX. Vibrational
      and isomer assignments of the IRMPD spectra are accomplished by density
      functional theory calculations at the B3LYP/cc-pVDZ level, which provide insight
      into the structure, binding energy, bonding mechanism, and spectral properties of
      the complexes. The two major binding sites identified involve metal bonding to
      the oxygen atoms of the two available carbonyl groups of LC (denoted O2 and O4).
      The more stable O4 isomer benefits from an additional interaction with the lone
      pair of the nearby N5 atom of LC. While M(+)LC with alkali metals are mainly
      stabilized by electrostatic forces, the Ag(+)LC complex reveals additional
      stabilization arising from partly covalent contributions. Finally, the
      interaction of Mg(2+) ions with LC is largely enhanced by the doubled positive
      charge. The frequencies of the C[double bond, length as m-dash]O stretching modes
      are a sensitive indicator of both the metal binding site and the metal bond
      strength. 

PMID- 24905968
TI  - Easy access to Ni3N- and Ni-carbon nanocomposite catalysts.
AB  - In the search for alternative materials to current expensive catalysts, Ni has
      been addressed as one of the most promising and, on this trail, its corresponding
      nitride. However, nickel nitride is a thermally unstable compound, and therefore
      not easy to prepare especially as nanoparticles. In the present work, a sol-gel
      based process (the urea glass route) is applied to prepare well-defined and
      homogeneous Ni3N and Ni nanoparticles. In both cases, the prepared crystalline
      nanoparticles (~25 nm) are dispersed in a carbon matrix forming interesting Ni3N-
      and Ni-based composites. These nanocomposites were characterised by means of
      several techniques, such as XRD, HR-TEM, EELS, and the reaction mechanism was
      investigated by TGA and IR and herein discussed. The catalytic activity of Ni3N
      is investigated for the first time, to the best of our knowledge, for
      hydrogenation reactions involving H2, and here compared to the one of Ni. Both
      materials show good catalytic activities but, interestingly, give a different
      selectivity between different functional groups (namely, nitro, alkene and
      nitrile groups).

PMID- 24905967
TI  - Relative safety of peginesatide and epoetin alfa.
AB  - PURPOSE: Peginesatide, a long-acting erythropoiesis-stimulating agent, was
      recalled in February 2013 following reports of serious and sometimes fatal
      hypersensitivity reactions in dialysis patients who received a first dose. We
      assessed the relative risks of mortality and morbidity in peginesatide-treated
      and matched epoetin alfa-treated patients. METHODS: From standardized extracts of
      paid Medicare claims in 2012 and 2013, we identified dialysis patients treated
      with peginesatide or epoetin between 1 July 2012 and 28 February 2013. For each
      peginesatide-treated patient, we identified with propensity score matching two
      epoetin-treated control patients. Patients were followed for up to 2 days after
      the first peginesatide dose or the referent epoetin dose for death or
      hospitalization as a result of cardiovascular morbidity or symptoms (composite
      event), all-cause hospitalization, and emergency room care. RESULTS: We
      identified 15 633 peginesatide-treated patients and 31 266 matched epoetin
      treated controls. On the day of dose administration, 19 composite events occurred
      with peginesatide (incidence, 0.12%) and 14 with epoetin (0.04%); the hazard
      ratio was 2.7 (95% confidence interval, 1.4-5.4). With follow-up for 1 and 2
      subsequent days, hazard ratios were 1.6 (1.0-2.4) and 1.5 (1.1-2.0),
      respectively. Corresponding hazard ratios were larger among hemodialysis patients
      with neither intravenous antibiotic nor intravenous iron exposure on the day of
      dose administration. Hazard ratios for all-cause hospitalization and emergency
      room care exceeded 1 on and after the day of dose administration. CONCLUSIONS:
      Relative to administration of epoetin alfa, first administration of peginesatide
      in dialysis patients was acutely associated with higher risk of death or
      hospitalization as a result of cardiovascular morbidity or symptoms.

PMID- 24905969
TI  - Commentary on "videoendoscopic single-port nipple-sparing mastectomy and
      immediate reconstruction".

PMID- 24905970
TI  - Safe and cost-effective control of post-transplantation recurrence of hepatitis
      B.
AB  - A combination of hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide
      analogs (NUC) is the current standard of care for controlling hepatitis B
      recurrence after orthotopic liver transplantation (OLT). However, long-term HBIG
      administration is associated with several unresolved issues, including limited
      availability and extremely high cost, and thus several protocols for treatment
      with low-dose HBIG combined with NUC or HBIG-free regimens have been developed.
      This article reviews recent advances in post-OLT hepatitis B virus (HBV) control
      and future methodological directions. New NUC such as entecavir, tenofovir or
      lamivudine plus adefovir dipivoxil combinations induce a very low frequency of
      viral resistance. The withdrawal of HBIG after several months of OLT under new
      NUC continuation also has permissible effects. Even after HBV reactivation, NUC
      can usually achieve viral control when viral markers are strictly followed up.
      Another approach is to induce self-producing anti-HBV antibodies via vaccination
      with a hepatitis B surface antigen vaccine. However, HBV vaccination is not
      sufficiently effective in patients to treat liver cirrhosis type B after OLT
      because immune tolerance to the virus has already continued for several decades.
      Trials of its safety and cost-effectiveness are required. This review advocates a
      safe and economical approach to controlling post-OLT HBV recurrence. 

PMID- 24905972
TI  - Decoding pattern motion information in V1.
AB  - When two gratings drifting in different directions are superimposed, the
      resulting stimulus can be perceived as two overlapping component gratings moving
      in different directions or as a single pattern moving in one direction. Whilst
      the motion direction of component gratings is already represented in visual area
      V1, the majority of previous studies have found processing of pattern motion
      direction only from visual area V2 onwards. Here, we question these findings
      using multi-voxel pattern analysis (MVPA). In Experiment 1, we presented
      superimposed sinusoidal gratings with varying angles between the two component
      motions. These stimuli were perceived as patterns moving in one of two possible
      directions. We found that linear support vector machines (SVMs) could generalise
      across stimuli composed of different component motions to successfully
      discriminate pattern motion direction from brain activity in V1, V3A and hMT+/V5.
      This demonstrates the representation of pattern motion information present in
      these visual areas. This conclusion was verified in Experiment 2, where we
      manipulated similar plaid stimuli to induce the perception of either a single
      moving pattern or two separate component gratings. While a classifier could again
      generalise across stimuli composed of different component motions when they were
      perceived as a single moving pattern, its performance dropped substantially in
      the case where components were perceived. Our results indicate that pattern
      motion direction information is present in V1. 

PMID- 24905971
TI  - Aberrant functional connectivity in Papez circuit correlates with memory
      performance in cognitively intact middle-aged APOE4 carriers.
AB  - The main objective of this study is to detect the early changes in resting-state
      Papez circuit functional connectivity using the hippocampus as the seed, and to
      determine the associations between altered functional connectivity (FC) and the
      episodic memory performance in cognitively intact middle-aged apolipoprotein E4
      (APOE4) carriers who are at risk of Alzheimer's disease (AD). Forty-six
      cognitively intact, middle-aged participants, including 20 APOE4 carriers and 26
      age-, sex-, and education-matched noncarriers were studied. The resting-state FC
      of the hippocampus (HFC) was compared between APOE4 carriers and noncarriers.
      APOE4 carriers showed significantly decreased FC in brain areas that involve
      learning and memory functions, including the frontal, cingulate, thalamus and
      basal ganglia regions. Multiple linear regression analysis showed significant
      correlations between HFC and the episodic memory performance. Conjunction
      analysis between neural correlates of memory and altered HFC showed the
      overlapping regions, especially the subcortical regions such as thalamus, caudate
      nucleus, and cingulate cortices involved in the Papez circuit. Thus, changes in
      connectivity in the Papez circuit may be used as an early risk detection for AD. 

PMID- 24905973
TI  - Design and construction of higher-order structure and function in proteinosome
      based protocells.
AB  - The design and construction of higher-order structure and function in
      proteinosome microcompartments enclosed by a cross-linked membrane of amphiphilic
      bovine serum albumin/poly(N-isopropylacrylamide) (BSA-NH2/PNIPAAm) nanoconjugates
      is described. Three structure/function relationships are investigated: (i)
      differential chemical cross-linking for the control of membrane disassembly and
      regulated release of encapsulated genetic polymers; (ii) enzyme-mediated hydrogel
      structuring of the internal microenvironment to increase mechanical robustness
      and generate a molecularly crowded reaction environment; and (iii) self
      production of a membrane-enclosing outer hydrogel wall for generating protease
      resistant forms of the protein-polymer protocells. Our results highlight the
      potential of integrating aspects of supramolecular and polymer chemistry into the
      design and construction of novel bioinspired microcompartments as a step toward
      small-scale materials systems based on synthetic cellularity. 

PMID- 24905974
TI  - Effect of subinhibitory concentrations of chlorogenic acid on reducing the
      virulence factor production by Staphylococcus aureus.
AB  - Chlorogenic acid (CA) has been reported to inhibit several pathogens, but the
      influence of subinhibitory concentrations of CA on virulence expression of
      pathogens has not been fully elucidated. The aim of this study was to explore the
      effect of CA on the virulence factor production of Staphylococcus aureus. The
      minimum inhibitory concentration (MIC) of CA against S. aureus was determined
      using a broth microdilution method. Hemolysin assays, coagulase titer assays,
      adherence to solid-phase fibrinogen assays, Western blot, and real-time reverse
      transcriptase-polymerase chain reaction were performed to evaluate the effect of
      subinhibitory concentrations of CA on the virulence factors of S. aureus. MIC of
      CA against S. aureus ATCC29213 was found to be 2.56 mg/mL. At subinhibitory
      concentrations, CA significantly inhibited the hemolysis and dose-dependently
      decreased coagulase titer. Reduced binding to fibrinogen and decreased production
      of SEA were observed with treatment of CA at concentrations ranging from 1/16MIC
      to 1/2MIC. CA markedly inhibited the expression of hla, sea, and agr genes in S.
      aureus. These data demonstrate that the virulence expression of S. aureus could
      be reduced by CA and suggest that CA could be potentially developed as a
      supplemental strategy to control S. aureus infection and to prevent
      staphylococcal food poisoning.

PMID- 24905976
TI  - Determinants and Strategies for Physical Activity Maintenance in Chronic Health
      Conditions: A Qualitative Study.
AB  - BACKGROUND: Physical activity is promoted to help adults manage chronic health
      conditions, but evidence suggests that individuals relapse after intervention
      cessation. The objective of this study was to explore the determinants and
      strategies for successful and unsuccessful physical activity maintenance.
      METHODS: A qualitative study using semistructured interviews was conducted with
      32 participants. Purposive sampling was used to recruit 20 successful and 12
      unsuccessful maintainers. Adults with chronic health conditions were recruited
      having completed a physical activity referral scheme 6 months before study
      commencement. The IPAQ and SPAQ were used to categorize participants according to
      physical activity status. Data were analyzed using framework analysis. RESULTS:
      Eleven main themes emerged: 1) outcome expectations, 2) experiences, 3) core
      values, 4) trial and error, 5) social and practical support, 6) attitudes toward
      physical activity, 7) environmental barriers, 8) psychological barriers, 9)
      physical barriers, 10) cognitive-behavioral strategies for physical activity self
      management (eg, self-monitoring), and 11) condition management (eg, pacing).
      CONCLUSIONS: The findings identified determinants and strategies for successful
      maintenance and highlighted the processes involved in physical activity
      disengagement. Such findings can guide the development of physical activity
      maintenance interventions and increase activity engagement over the long-term in
      adults with chronic health conditions.

PMID- 24905975
TI  - sdf1 Expression reveals a source of perivascular-derived mesenchymal stem cells
      in zebrafish.
AB  - There is accumulating evidence that mesenchymal stem cells (MSCs) have their
      origin as perivascular cells (PVCs) in vivo, but precisely identifying them has
      been a challenge, as they have no single definitive marker and are rare. We have
      developed a fluorescent transgenic vertebrate model in which PVC can be
      visualized in vivo based upon sdf1 expression in the zebrafish. Prospective
      isolation and culture of sdf1(DsRed) PVC demonstrated properties consistent with
      MSC including prototypical cell surface marker expression; mesodermal
      differentiation into adipogenic, osteogenic, and chondrogenic lineages; and the
      ability to support hematopoietic cells. Global proteomic studies performed by two
      dimensional liquid chromatography and tandem mass spectrometry revealed a high
      degree of similarity to human MSC (hMSC) and discovery of novel markers (CD99,
      CD151, and MYOF) that were previously unknown to be expressed by hMSC. Dynamic in
      vivo imaging during fin regeneration showed that PVC may arise from
      undifferentiated mesenchyme providing evidence of a PVC-MSC relationship. This is
      the first model, established in zebrafish, in which MSC can be visualized in vivo
      and will allow us to better understand their function in a native environment.

PMID- 24905978
TI  - Strong cooperative effect of oppositely charged surfactant mixtures on their
      adsorption and packing at the air-water interface and interfacial water
      structure.
AB  - Remarkable adsorption enhancement and packing of dilute mixtures of water-soluble
      oppositely-charged surfactants, sodium dodecyl sulfate (SDS) and dodecyl amine
      hydrochloride (DAH), at the air-water interface were observed by using sum
      frequency generation spectroscopy and tensiometry. The interfacial water
      structure was also observed to be significantly influenced by the SDS-DAH
      mixtures, differently from the synergy of the single surfactants. Most
      strikingly, the obtained spectroscopic evidence suggests that the interfacial
      hydrophobic alkyl chains of the binary mixtures assemble differently from those
      of single surfactants. This study highlights the significance of the cooperative
      interaction between the headgroups of oppositely charged binary surfactant
      systems and subsequently provides some insightful observations about the
      molecular structure of the air-aqueous interfacial water molecules and, more
      importantly, about the packing nature of the surfactant hydrophobic chains of
      dilute SDS-DAH mixtures of concentration below 1% of the CMC. 

PMID- 24905977
TI  - Modes and mechanisms of T cell motility: roles for confinement and Myosin-IIA.
AB  - T cells are charged with surveying tissues for evidence of their cognate foreign
      antigens. Subsequently, they must navigate to effector sites, which they enter
      through the process of trans-endothelial migration (TEM). During interstitial
      migration, T cells migrate according to one of two modes that are distinguished
      by the strength and sequence of adhesions and the requirement for Myosin-IIA. In
      contrast during TEM, T cells require Myosin-IIA for the final process of pushing
      their nucleus through the endothelium. A generalized model emerges with dual
      roles for Myosin-IIA: This motor protein acts like a tensioning or expansion
      spring, transmitting force across the cell cortex to sites of surface contact and
      also optimizing the frictional coupling with substrata by modulating the surface
      area of the contact. The phosphorylation and deactivation of this motor following
      TCR engagement can allow T cells to rapidly alter the degree to which they adhere
      to surfaces and to switch to a mode of interaction with surfaces that is more
      conducive to forming a synapse with an antigen-presenting cell. 

PMID- 24905979
TI  - Construction and expression of a novel anti-CD14 human-mouse chimeric antibody
      Hm2F9.
AB  - Anti-CD14 antibody can inhibit the lipopolysaccharide (LPS)-induced systemic
      inflammatory response syndrome in case of bacteremia or endotoxemia. To obtain
      chimeric anti-CD14 antibody, we constructed and expressed a novel chimeric
      antibody Hm2F9 composed of anti-CD14 single-chain fragment variable (scFv) and
      the Fc region (the hinge, CH2, and CH3 domains) of human IgG1 in Chinese hamster
      ovary (CHO) cells based on our previous study of scFv2F9. The Hm2F9 antibody,
      sized 150 kDa, retained the strong specific antigen-binding ability to the CD14
      antigen with a comparable activity (the percentage of positive cells 99.07%) to
      its parental murine antibody 2F9 (the percentage of positive cells 98.86%). At
      the same time, Hm2F9 could manifestly block the binding of LPS to CD14, whose
      positive-cell percentage drops significantly with percentage of 98.63% (from
      98.37% to 1.35%). The chimeric antibody Hm2F9 expressed in CHO cells retained
      high affinity to human CD14 and biological function to LPS.

PMID- 24905980
TI  - Activation of muscle enhancers by MyoD and epigenetic modifiers.
AB  - The early 1980s revelation of cis-acting genomic elements, known as
      transcriptional enhancers, is still regarded as one of the fundamental
      discoveries in the genomic field. However, only with the emergence of genome-wide
      techniques has the genuine biological scope of enhancers begun to be fully
      uncovered. Massive scientific efforts of multiple laboratories rapidly advanced
      the overall perception that enhancers are typified by common epigenetic
      characteristics that distinguish their activating potential. Broadly, chromatin
      modifiers and transcriptional regulators lay down the essential foundations
      necessary for constituting enhancers in their activated form. Basing on genome
      wide ChIP-sequencing of enhancer-related marks we identified myogenic enhancers
      before and after muscle differentiation and discovered that MyoD was bound to
      nearly a third of condition-specific enhancers. Experimental studies that tested
      the deposition patterns of enhancer-related epigenetic marks in MyoD-null
      myoblasts revealed the high dependency that a specific set of muscle enhancers
      have towards this transcriptional regulator. Re-expression of MyoD restored the
      deposition of enhancer-related marks at myotube-specific enhancers and partially
      at myoblasts-specific enhancers. Our proposed mechanistic model suggests that
      MyoD is involved in recruitment of methyltransferase Set7, acetyltransferase p300
      and deposition of H3K4me1 and H3K27ac at myogenic enhancers. In addition, MyoD
      binding at enhancers is associated with PolII occupancy and with local noncoding
      transcription. Modulation of muscle enhancers is suggested to be coordinated via
      transcription factors docking, including c-Jun and Jdp2 that bind to muscle
      enhancers in a MyoD-dependent manner. We hypothesize that distinct transcription
      factors may act as placeholders and mediate the assembly of newly formed myogenic
      enhancers.

PMID- 24905981
TI  - Proliferation of neutral modes in fractional quantum Hall states.
AB  - The fractional quantum Hall effect is a canonical example of topological phases.
      While electric currents flow downstream in edge modes, neutral edge modes,
      observed only in hole-conjugate states and in nu=5/2, flow upstream. It is
      believed that the latter transport results from multiple counter-propagating
      channels-mixed by disorder that is accompanied by Coulomb interaction. Here we
      report on sensitive shot noise measurements that reveal unexpected presence of
      neutral modes in non-hole-conjugate fractional states; however, not in the
      integer states. Furthermore, the incompressible bulk is also found to allow
      energy transport. While density reconstructions along the edge may account for
      the energy carrying edge modes, the origin of the bulk energy modes is
      unidentified. The proliferation of neutral modes changes drastically the accepted
      transport picture of the fractional quantum Hall effects. Their apparent
      ubiquitous presence may explain the lack of interference of fractional
      quasiparticles-preventing observation of fractional statistics.

PMID- 24905982
TI  - Production and characterization of monoclonal antibodies against horse
      immunoglobulins useful for the diagnosis of equine diseases.
AB  - Monoclonal antibodies (MAbs) against horse IgG were produced by immunizing Balb/c
      mice with purified horse IgG and were characterized in indirect ELISA versus
      purified immunoglobulins from donkey, cow, buffalo, sheep, pig, and chicken.
      Three MAbs (1B10B6C9, 1B10B6C10, 1B10B6E9) reacted only with horse and donkey IgG
      and IgM and, in western blotting, were specific for the Fc fragment of equine
      IgG. MAb 1B10B6E9 was used in chemiluminescent immunoblotting assay for the
      diagnosis of dourine and in indirect immunofluorescence assay (IFA) for the
      diagnosis of African horse sickness and dourine. 

PMID- 24905983
TI  - Luminescence modulations of rhenium tricarbonyl complexes induced by structural
      variations.
AB  - Octahedral d(6) low-spin Re(I) tricarbonyl complexes are of considerable interest
      as noninvasive imaging probes and have been deeply studied owing to their
      biological stability, low toxicity, large Stokes shifts, and long luminescence
      lifetimes. We reported recently the bimodal IR and luminescence imaging of a
      Re(I) tricarbonyl complex with a Pyta ligand (4-(2-pyridyl)-1,2,3-triazole) in
      cells and labeled such metal-carbonyl complexes SCoMPIs for single-core
      multimodal probes for imaging. Re(I) tricarbonyl complexes have unique
      photophysical properties allowing for their unequivocal detection in cells but
      also present some weaknesses such as a very low luminescence quantum yield in
      aqueous medium. Further optimizations would thus be desirable. We therefore
      developed new Re(I) tricarbonyl complexes prepared from different ancillary
      ligands. Complexes with benzothiadiazole-triazole ligands show interesting
      luminescent quantum yields in acetonitrile and may constitute valuable
      luminescent metal complexes in organic media. A series of complexes with
      bidentate 1-(2-quinolinyl)-1,2,3-triazole (Taquin) and 1-(2-pyridyl)-1,2,3
      triazole (Tapy) ligands bearing various 4-substituted alkyl side chains has been
      designed and synthesized with efficient procedures. Their photophysical
      properties have been characterized in acetonitrile and in a H2O/DMSO (98/2)
      mixture and compared with those of the parent Quinta- and Pyta-based complexes.
      Tapy complexes bearing long alkyl chains show impressive enhancement of their
      luminescent properties relative to the parent Pyta complex. Theoretical
      calculations have been performed to further characterize this new class of
      rhenium tricarbonyl complexes. Preliminary cellular imaging studies in MDA-MB231
      breast cancer cells reveal a strong increase in the luminescence signal in cells
      incubated with the Tapy complex substituted with a C12 alkyl chain. This study
      points out the interesting potential of the Tapy ligand in coordination
      chemistry, which has been so far underexploited. 

PMID- 24905984
TI  - Risk prediction scores for recurrence and progression of non-muscle invasive
      bladder cancer: an international validation in primary tumours.
AB  - OBJECTIVE: We aimed to determine the validity of two risk scores for patients
      with non-muscle invasive bladder cancer in different European settings, in
      patients with primary tumours. METHODS: We included 1,892 patients with primary
      stage Ta or T1 non-muscle invasive bladder cancer who underwent a transurethral
      resection in Spain (n = 973), the Netherlands (n = 639), or Denmark (n = 280). We
      evaluated recurrence-free survival and progression-free survival according to the
      European Organisation for Research and Treatment of Cancer (EORTC) and the
      Spanish Urological Club for Oncological Treatment (CUETO) risk scores for each
      patient and used the concordance index (c-index) to indicate discriminative
      ability. RESULTS: The 3 cohorts were comparable according to age and sex, but
      patients from Denmark had a larger proportion of patients with the high stage and
      grade at diagnosis (p<0.01). At least one recurrence occurred in 839 (44%)
      patients and 258 (14%) patients had a progression during a median follow-up of 74
      months. Patients from Denmark had the highest 10-year recurrence and progression
      rates (75% and 24%, respectively), whereas patients from Spain had the lowest
      rates (34% and 10%, respectively). The EORTC and CUETO risk scores both predicted
      progression better than recurrence with c-indices ranging from 0.72 to 0.82 while
      for recurrence, those ranged from 0.55 to 0.61. CONCLUSION: The EORTC and CUETO
      risk scores can reasonably predict progression, while prediction of recurrence is
      more difficult. New prognostic markers are needed to better predict recurrence of
      tumours in primary non-muscle invasive bladder cancer patients.

PMID- 24905985
TI  - Construction and analysis of high-density linkage map using high-throughput
      sequencing data.
AB  - Linkage maps enable the study of important biological questions. The construction
      of high-density linkage maps appears more feasible since the advent of next
      generation sequencing (NGS), which eases SNP discovery and high-throughput
      genotyping of large population. However, the marker number explosion and
      genotyping errors from NGS data challenge the computational efficiency and
      linkage map quality of linkage study methods. Here we report the HighMap method
      for constructing high-density linkage maps from NGS data. HighMap employs an
      iterative ordering and error correction strategy based on a k-nearest neighbor
      algorithm and a Monte Carlo multipoint maximum likelihood algorithm. Simulation
      study shows HighMap can create a linkage map with three times as many markers as
      ordering-only methods while offering more accurate marker orders and stable
      genetic distances. Using HighMap, we constructed a common carp linkage map with
      10,004 markers. The singleton rate was less than one-ninth of that generated by
      JoinMap4.1. Its total map distance was 5,908 cM, consistent with reports on low
      density maps. HighMap is an efficient method for constructing high-density, high
      quality linkage maps from high-throughput population NGS data. It will facilitate
      genome assembling, comparative genomic analysis, and QTL studies. HighMap is
      available at http://highmap.biomarker.com.cn/. 

PMID- 24905986
TI  - Do flower color and floral scent of silene species affect host preference of
      Hadena bicruris, a seed-eating pollinator, under field conditions?
AB  - Specialization in plant-insect interactions is an important driver of
      evolutionary divergence; yet, plant traits mediating such interactions are poorly
      understood. In this study, we investigated how flower color and floral scent are
      related to seed predation by a seed-eating pollinator. We used field-transplanted
      recombinant F2 hybrids between Silene latifolia and S. dioica that are the
      preferred and alternative hosts of the moth Hadena bicruris and crosses within
      these species for comparison. We scored seed predation and flower color and
      analyzed floral scent. Pinker S. dioica-like flowers and emission of alpha-pinene
      decreased the odds of seed predation while emission of benzyl acetate and 6
      methyl-5-hepten-2-one increased the odds of seed predation. Emission of these
      compounds did not differ significantly between the two Silene species. Our
      results suggest that flower color plays an important role in the specific
      interaction of H. bicruris with its preferred host S. latifolia. The compounds
      alpha-pinene, benzyl acetate and 6-methyl-5-hepten-2-one could represent non
      specific deterrents and attractants to ovipositing moths. Alternatively, emission
      of these compounds could be related to herbivory or pathogen attack and act as a
      signal for host quality. This would weaken the predictability of the plant's
      costs and benefits of the interaction and act to maintain an imperfect degree of
      specialization. 

PMID- 24905988
TI  - Nuclear positioning by actin cables and perinuclear actin: Special and general?
AB  - Nuclear positioning is an important process during development and homeostasis.
      Depending on the affected tissue, mislocalized nuclei can alter cellular
      processes such as polarization, differentiation, or migration and lead ultimately
      to diseases. Many cells actively control the position of their nucleus using
      their cytoskeleton and motor proteins. We have recently shown that during
      Drosophila oogenesis, nurse cells employ cytoplasmic actin cables in association
      with perinuclear actin to position their nucleus. Here, we briefly summarize our
      work and discuss why nuclear positioning in nurse cells is specialized but the
      molecular mechanisms are likely to be more generally used. 

PMID- 24905990
TI  - 'One-stop shopping' for information on conducting systematic reviews and meta
      analysis in animal agriculture and veterinary medicine.

PMID- 24905991
TI  - Introduction to systematic reviews in animal agriculture and veterinary medicine.
AB  - This article is the first in a series of six articles related to systematic
      reviews in animal agriculture and veterinary medicine. In this article, we
      overview the methodology of systematic reviews and provide a discussion of their
      use. Systematic reviews differ qualitatively from traditional reviews by
      explicitly defining a specific review question, employing methods to reduce bias
      in the selection and inclusion of studies that address the review question
      (including a systematic and specified search strategy, and selection of studies
      based on explicit eligibility criteria), an assessment of the risk of bias for
      included studies and objectively summarizing the results qualitatively or
      quantitatively (i.e. via meta-analysis). Systematic reviews have been widely used
      to address human healthcare questions and are increasingly being used in
      veterinary medicine. Systematic reviews can provide veterinarians and other
      decision-makers with a scientifically defensible summary of the current state of
      knowledge on a topic without the need for the end-user to read the vast amount of
      primary research related to that topic. 

PMID- 24905987
TI  - Inferior parietal lobule encodes visual temporal resolution processes
      contributing to the critical flicker frequency threshold in humans.
AB  - The measurement of the Critical Flicker Frequency threshold is used to study the
      visual temporal resolution in healthy subjects and in pathological conditions. To
      better understand the role played by different cortical areas in the Critical
      Flicker Frequency threshold perception we used continuous Theta Burst Stimulation
      (cTBS), an inhibitory plasticity-inducing protocol based on repetitive
      transcranial magnetic stimulation. The Critical Flicker Frequency threshold was
      measured in twelve healthy subjects before and after cTBS applied over different
      cortical areas in separate sessions. cTBS over the left inferior parietal lobule
      altered the Critical Flicker Frequency threshold, whereas cTBS over the left
      mediotemporal cortex, primary visual cortex and right inferior parietal lobule
      left the Critical Flicker Frequency threshold unchanged. No statistical
      difference was found when the red or blue lights were used. Our findings show
      that left inferior parietal lobule is causally involved in the conscious
      perception of Critical Flicker Frequency and that Critical Flicker Frequency
      threshold can be modulated by plasticity-inducing protocols. 

PMID- 24905992
TI  - Study designs and systematic reviews of interventions: building evidence across
      study designs.
AB  - This article is the second article in a series of six focusing on systematic
      reviews in animal agriculture and veterinary medicine. This article addresses the
      strengths and limitations of study designs commonly used in animal agriculture
      and veterinary research to assess interventions (preventive or therapeutic
      treatments) and discusses the appropriateness of their use in systematic reviews
      of interventions. Different study designs provide different evidentiary value for
      addressing questions about the efficacy of interventions. Experimental study
      designs range from in vivo proof of concept experiments to randomized controlled
      trials (RCTs) under real-world conditions. The key characteristic of experimental
      design in intervention studies is that the investigator controls the allocation
      of individuals or groups to different intervention strategies. The RCT is
      considered the gold standard for evaluating the efficacy of interventions and, if
      there are well-executed RCTs available for inclusion in a systematic review, that
      review may be restricted to only this design. In some instances, RCTs may not be
      feasible or ethical to perform, and there are fewer RCTs published in the
      veterinary literature compared to the human healthcare literature. Therefore,
      observational study designs, where the investigator does not control intervention
      allocation, may provide the only available evidence of intervention efficacy.
      While observational studies tend to be relevant to real-world use of an
      intervention, they are more prone to bias. Human healthcare researchers use a
      pyramid of evidence diagram to describe the evidentiary value of different study
      designs for assessing interventions. Modifications for veterinary medicine are
      presented in this article. 

PMID- 24905993
TI  - Randomized controlled trials and challenge trials: design and criterion for
      validity.
AB  - This article is the third of six articles addressing systematic reviews in animal
      agriculture and veterinary medicine. This article provides an overview of
      clinical trials, both randomized controlled trials (RCTs) and challenge trials,
      where the disease outcome is deliberately induced by the investigator. RCTs are
      not the only study design used in systematic reviews, but are preferred when
      available as the gold standard for evaluating interventions under real-world
      conditions. RCTs are planned experiments, which involve diseased or at-risk study
      subjects and are designed to evaluate interventions (therapeutic treatments or
      preventive strategies, including antibiotics, vaccines, management practices,
      dietary changes, management changes or lifestyle changes). Key components of the
      RCT are the use of one or more comparison (control) groups and investigator
      control over intervention allocation. Important design features in RCTs include
      as follows: how the population is selected, approach to allocation of
      intervention and control group subjects, how allocation is concealed prior to
      enrolment of study subjects, how outcomes are defined, how allocation to group is
      concealed (blinding) and how withdrawals from the study are managed. Guidelines
      for reporting important features of RCTs have been published and are useful tools
      for writing, reviewing and reading reports of RCTs. 

PMID- 24905994
TI  - Conducting systematic reviews of intervention questions I: Writing the review
      protocol, formulating the question and searching the literature.
AB  - This article is the fourth of six articles addressing systematic reviews in
      animal agriculture and veterinary medicine. Previous articles in the series have
      introduced systematic reviews, discussed study designs and hierarchies of
      evidence, and provided details on conducting randomized controlled trials, a
      common design for use in systematic reviews. This article describes development
      of a review protocol and the first two steps in a systematic review: formulating
      a review question, and searching the literature for relevant research. The
      emphasis is on systematic reviews of questions related to interventions. The
      review protocol is developed prior to conducting the review and specifies the
      plan for the conduct of the review, identifies the roles and responsibilities of
      the review team and provides structured definitions related to the review
      question. For intervention questions, the review question should be defined by
      the PICO components: population, intervention, comparison and outcome(s). The
      literature search is designed to identify all potentially relevant original
      research that may address the question. Search terms related to some or all of
      the PICO components are entered into literature databases, and searches for
      unpublished literature also are conducted. All steps of the literature search are
      documented to provide transparent reporting of the process. 

PMID- 24905995
TI  - Conducting systematic reviews of intervention questions II: Relevance screening,
      data extraction, assessing risk of bias, presenting the results and interpreting
      the findings.
AB  - This is the fifth in a series of six articles describing systematic reviews in
      animal agriculture and veterinary medicine. The previous articles in this series
      overviewed the development of a review protocol and the initial steps in
      conducting a systematic review: identification of a structured question to be
      answered and conducting a comprehensive literature search to find potentially
      relevant original research to address the review question. This article describes
      relevance screening of literature identified in the search to determine which of
      the original research articles are relevant to the review question, data
      extraction from primary research studies, the use of standardized procedures to
      assess the risk of bias in the relevant research studies, presenting the results
      of the body of research identified and interpreting these results. 

PMID- 24905996
TI  - Conducting systematic reviews of intervention questions III: Synthesizing data
      from intervention studies using meta-analysis.
AB  - This article is the sixth in a series of six articles describing systematic
      reviews of interventions in animal agriculture and veterinary medicine. The first
      article provided an overview of systematic reviews, followed by an article on
      building evidence across study designs, and an article describing criteria for
      validity in randomized controlled trials. The fourth article in this series
      overviewed the initial steps in conducting a systematic review: development of a
      review protocol, identification of the structured question to be addressed and
      conducting a comprehensive literature search to identify potentially relevant
      research to address the review question. The fifth article introduced relevance
      screening of literature to identify and include research that is relevant to the
      review question, the use of standardized checklists and procedures to assess the
      risk of bias in the relevant research, data extraction from primary research
      studies and summarizing the results of the body of research identified. Many
      systematic reviews of interventions aim to use a quantitative method to combine
      the results of multiple studies and provide a more precise estimate of the effect
      of the intervention on the outcome, that is, a summary effect measure. The
      objective of this article was to describe general approaches that are available
      for quantitative synthesis of data. Specific details of all meta-analysis
      statistical approaches are beyond the capacity of this article. 

PMID- 24905998
TI  - Long term effect of land reclamation from lake on chemical composition of soil
      organic matter and its mineralization.
AB  - Since the late 1950s, land reclamation from lakes has been a common human
      disturbance to ecosystems in China. It has greatly diminished the lake area, and
      altered natural ecological succession. However, little is known about its impact
      on the carbon (C) cycle. We conducted an experiment to examine the variations of
      chemical properties of dissolved organic matter (DOM) and C mineralization under
      four land uses, i.e. coniferous forest (CF), evergreen broadleaf forest (EBF),
      bamboo forest (BF) and cropland (CL) in a reclaimed land area from Taihu Lake.
      Soils and lake sediments (LS) were incubated for 360 days in the laboratory and
      the CO2 evolution from each soil during the incubation was fit to a double
      exponential model. The DOM was analyzed at the beginning and end of the
      incubation using UV and fluorescence spectroscopy to understand the relationships
      between DOM chemistry and C mineralization. The C mineralization in our study was
      influenced by the land use with different vegetation and management. The greatest
      cumulative CO2-C emission was observed in BF soil at 0-10 cm depth. The active C
      pool in EBF at 10-25 cm had longer (62 days) mean residence time (MRT). LS showed
      the highest cumulative CO2-C and shortest MRT comparing with the terrestrial
      soils. The carbohydrates in DOM were positively correlated with CO2-C evolution
      and negatively correlated to phenols in the forest soils. Cropland was
      consistently an outlier in relationships between DOM chemistry and CO2-evolution,
      highlighting the unique effects that this land use on soil C cycling, which may
      be attributed the tillage practices. Our results suggest that C mineralization is
      closely related to the chemical composition of DOM and sensitive to its
      variation. Conversion of an aquatic ecosystem into a terrestrial ecosystem may
      alter the chemical structure of DOM, and then influences soil C mineralization. 

PMID- 24905999
TI  - A combined theoretical and experimental study of the influence of different anion
      ratios on lithium ion dynamics in ionic liquids.
AB  - In this paper, we investigate via experimental and simulation techniques the
      transport properties, in terms of total ionic conductivity and ion diffusion
      coefficients, of ionic liquids doped with lithium salts. They are composed of two
      anions, bis(fluorosulfonyl)imide (FSI) and bis(trifluoromethanesulfonyl)imide
      (TFSI), and two cations, N-ethyl-N-methylimidazolium (emim) and lithium ions. The
      comparison of the experimental results with the simulations shows very good
      agreement over a wide temperature range and a broad range of compositions. The
      addition of TFSI gives rise to the formation of lithium dimers (Li(+)-TFSI(-)
      Li(+)). A closer analysis of such dimers shows that involved lithium ions move
      nearly as fast as single lithium ions, although they have a different
      coordination and much slower TFSI exchange rates. 

PMID- 24905997
TI  - Autophagy regulates the therapeutic potential of mesenchymal stem cells in
      experimental autoimmune encephalomyelitis.
AB  - Mesenchymal stem cell (MSC)-based therapy is a promising approach to treat
      various inflammatory disorders including multiple sclerosis. However, the fate of
      MSCs in the inflammatory microenvironment is largely unknown. Experimental
      autoimmune encephalomyelitis (EAE) is a well-studied animal model of multiple
      sclerosis. We demonstrated that autophagy occurred in MSCs during their
      application for EAE treatment. Inflammatory cytokines, e.g., interferon gamma and
      tumor necrosis factor, induced autophagy in MSCs synergistically by inducing
      expression of BECN1/Beclin 1. Inhibition of autophagy by knockdown of Becn1
      significantly improved the therapeutic effects of MSCs on EAE, which was mainly
      attributable to enhanced suppression upon activation and expansion of CD4(+) T
      cells. Mechanistically, inhibition of autophagy increased reactive oxygen species
      generation and mitogen-activated protein kinase 1/3 activation in MSCs, which
      were essential for PTGS2 (prostaglandin-endoperoxide synthase 2 [prostaglandin
      G/H synthase and cyclooxygenase]) and downstream prostaglandin E2 expression to
      exert immunoregulatory function. Furthermore, pharmacological treatment of MSCs
      to inhibit autophagy increased their immunosuppressive effects on T cell-mediated
      EAE. Our findings indicate that inflammatory microenvironment-induced autophagy
      downregulates the immunosuppressive function of MSCs. Therefore, modulation of
      autophagy in MSCs would provide a novel strategy to improve MSC-based
      immunotherapy. 

PMID- 24906000
TI  - Targeting the Achilles' heel of drug-resistant cancer stem cells.

PMID- 24906002
TI  - Managing communication tensions and challenges during the end-of-life journey:
      perspectives of Maori kaumatua and their whanau.
AB  - The purpose of this study is to explore the cultural practices and communication
      tensions perceived among Maori kaumatua (elders) and their whanaunga (extended
      family) during the end-of-life journey. Further, the study aims to explore the
      manner in which the tensions are managed. The study was framed by relational
      dialectics theory and included interviews with 21 kaumatua and focus groups with
      39 whanau members. The study identified three cultural practices (dying at home,
      prayer, and song) that helped to build connection among the family members and
      also helped to connect the dying person to the spiritual world. Further, four
      communication tensions were noted: (a) autonomy and connection; (b) conflict and
      connection; (c) isolation and connection; and (d) balancing the needs of self and
      other. To manage these tensions, the following strategies were used: (a)
      coordination conversations; (b) inclusion in decision-making conversations; (c)
      emotional support within the whanau; and (d) passing on lessons to the next
      generation. 

PMID- 24906001
TI  - Archaeal Tuc1/Ncs6 homolog required for wobble uridine tRNA thiolation is
      associated with ubiquitin-proteasome, translation, and RNA processing system
      homologs.
AB  - While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6) and ubiquitin-related
      modifier-1 (Urm1) are important in the 2-thiolation of 5-methoxycarbonylmethyl-2
      thiouridine (mcm5s2U) at wobble uridines of tRNAs in eukaryotes, the biocatalytic
      roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we
      present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax
      volcanii) that is essential for maintaining cellular pools of thiolated
      tRNA(Lys)UUU and for growth at high temperature. When purified from Hfx.
      volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to
      polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1
      enzyme homolog of archaea (UbaA) was required for this covalent modification. Non
      covalent protein partners that specifically associated with NcsA were also
      identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN)-A/1,
      translation elongation factor aEF-1alpha and a beta-CASP ribonuclease homolog of
      the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1).
      Together, our study reveals that NcsA is essential for growth at high
      temperature, required for formation of thiolated tRNA(Lys)UUU and intimately
      linked to homologs of ubiquitin-proteasome, translation and RNA processing
      systems.

PMID- 24906003
TI  - Weighted multiplex networks.
AB  - One of the most important challenges in network science is to quantify the
      information encoded in complex network structures. Disentangling randomness from
      organizational principles is even more demanding when networks have a multiplex
      nature. Multiplex networks are multilayer systems of [Formula: see text] nodes
      that can be linked in multiple interacting and co-evolving layers. In these
      networks, relevant information might not be captured if the single layers were
      analyzed separately. Here we demonstrate that such partial analysis of layers
      fails to capture significant correlations between weights and topology of complex
      multiplex networks. To this end, we study two weighted multiplex co-authorship
      and citation networks involving the authors included in the American Physical
      Society. We show that in these networks weights are strongly correlated with
      multiplex structure, and provide empirical evidence in favor of the advantage of
      studying weighted measures of multiplex networks, such as multistrength and the
      inverse multiparticipation ratio. Finally, we introduce a theoretical framework
      based on the entropy of multiplex ensembles to quantify the information stored in
      multiplex networks that would remain undetected if the single layers were
      analyzed in isolation. 

PMID- 24906004
TI  - Computer modeling of a newly identified THRB gene mutation (S350L) associated
      with resistance to thyroid hormone in three unrelated patients.

PMID- 24906005
TI  - CRIF1 deficiency induces p66shc-mediated oxidative stress and endothelial
      activation.
AB  - Mitochondrial dysfunction has been implicated in the pathophysiology of various
      cardiovascular diseases. CRIF1 is a protein present in the mitochondria
      associated with large mitoribosomal subunits, and CRIF1 knockdown induces
      mitochondrial dysfunction and promotes ROS production. p66shc is a redox enzyme
      implicated in mitochondrial ROS generation and translation of oxidative signals
      and, therefore, is a key factor for oxidative stress in endothelial cells. In
      this study, we investigated whether mitochondrial dysfunction induced by CRIF1
      knockdown induces p66shc stimulation and plays any role in mitochondrial
      dysfunction-induced endothelial activation. Knockdown of CRIF1 decreased the
      expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, III
      and IV, leading to increased mitochondrial ROS (mtROS) and hyperpolarization of
      the mitochondrial membrane potential. Knockdown of CRIF1 also stimulated
      phosphorylation of p66shc and increased cytosolic ROS in endothelial cells.
      Furthermore, the expression of vascular cell adhesion molecule-1 and endoplasmic
      reticulum stress proteins were increased upon CRIF1 knockdown in endothelial
      cells. However, p66shc knockdown blunted the alteration in mitochondrial dynamics
      and ROS production in CRIF1 knockdown endothelial cells. In addition, p66shc
      knockdown reduced the CRIF1 knockdown-induced increases in adhesion between
      monocytes and endothelial cells. Taken together, these results suggest that CRIF1
      knockdown partially induces endothelial activation via increased ROS production
      and phosphorylation of p66shc. 

PMID- 24906007
TI  - Chronic hypoxia promotes pulmonary artery endothelial cell proliferation through
      H2O2-induced 5-lipoxygenase.
AB  - Pulmonary Hypertension (PH) is a progressive disorder characterized by
      endothelial dysfunction and proliferation. Hypoxia induces PH by increasing
      vascular remodeling. A potential mediator in hypoxia-induced PH development is
      arachidonate 5-Lipoxygenase (ALOX5). While ALOX5 metabolites have been shown to
      promote pulmonary vasoconstriction and endothelial cell proliferation, the
      contribution of ALOX5 to hypoxia-induced proliferation remains unknown. We
      hypothesize that hypoxia exposure stimulates HPAEC proliferation by increasing
      ALOX5 expression and activity. To test this, human pulmonary artery endothelial
      cells (HPAEC) were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions
      for 24-, 48-, or 72 hours. In a subset of cells, the ALOX5 inhibitor, zileuton,
      or the 5-lipoxygenase activating protein inhibitor, MK-886, was administered
      during hypoxia exposure. ALOX5 expression was measured by qRT-PCR and western
      blot and HPAEC proliferation was assessed. Our results demonstrate that 24 and 48
      hours of hypoxia exposure have no effect on HPAEC proliferation or ALOX5
      expression. Seventy two hours of hypoxia significantly increases HPAEC ALOX5
      expression, hydrogen peroxide (H2O2) release, and HPAEC proliferation. We also
      demonstrate that targeted ALOX5 gene silencing or inhibition of the ALOX5 pathway
      by pharmacological blockade attenuates hypoxia-induced HPAEC proliferation.
      Furthermore, our findings indicate that hypoxia-induced increases in cell
      proliferation and ALOX5 expression are dependent on H2O2 production, as
      administration of the antioxidant PEG-catalase blocks these effects and addition
      of H2O2 to HPAEC promotes proliferation. Overall, these studies indicate that
      hypoxia exposure induces HPAEC proliferation by activating the ALOX5 pathway via
      the generation of H2O2. 

PMID- 24906009
TI  - Self-organising maps and correlation analysis as a tool to explore patterns in
      excitation-emission matrix data sets and to discriminate dissolved organic matter
      fluorescence components.
AB  - Dissolved organic matter (DOM) is a complex mixture of organic compounds,
      ubiquitous in marine and freshwater systems. Fluorescence spectroscopy, by means
      of Excitation-Emission Matrices (EEM), has become an indispensable tool to study
      DOM sources, transport and fate in aquatic ecosystems. However the statistical
      treatment of large and heterogeneous EEM data sets still represents an important
      challenge for biogeochemists. Recently, Self-Organising Maps (SOM) has been
      proposed as a tool to explore patterns in large EEM data sets. SOM is a pattern
      recognition method which clusterizes and reduces the dimensionality of input EEMs
      without relying on any assumption about the data structure. In this paper, we
      show how SOM, coupled with a correlation analysis of the component planes, can be
      used both to explore patterns among samples, as well as to identify individual
      fluorescence components. We analysed a large and heterogeneous EEM data set,
      including samples from a river catchment collected under a range of hydrological
      conditions, along a 60-km downstream gradient, and under the influence of
      different degrees of anthropogenic impact. According to our results, chemical
      industry effluents appeared to have unique and distinctive spectral
      characteristics. On the other hand, river samples collected under flash flood
      conditions showed homogeneous EEM shapes. The correlation analysis of the
      component planes suggested the presence of four fluorescence components,
      consistent with DOM components previously described in the literature. A
      remarkable strength of this methodology was that outlier samples appeared
      naturally integrated in the analysis. We conclude that SOM coupled with a
      correlation analysis procedure is a promising tool for studying large and
      heterogeneous EEM data sets. 

PMID- 24906010
TI  - Genetic analysis of leaf rust resistance in six durum wheat genotypes.
AB  - Leaf rust, caused by Puccinia triticina, is one of the main fungal diseases
      limiting durum wheat production. This study aimed to characterize previously
      undescribed genes for leaf rust resistance in durum wheat. Six different
      resistant durum genotypes were crossed to two susceptible International Maize and
      Wheat Improvement Center (CIMMYT) lines and the resulting F1, F2, and F3
      progenies were evaluated for leaf rust reactions in the field and under
      greenhouse conditions. In addition, allelism tests were conducted. The results of
      the study indicated that most genotypes carried single effective dominant or
      recessive seedling resistance genes; the only exception to this was genotype
      Gaza, which carried one adult plant and one seedling resistance gene. In
      addition, it was concluded that the resistance genes identified in the current
      study were neither allelic to LrCamayo or Lr61, nor were they related to Lr3 or
      Lr14a, the genes that already are either ineffective or are considered to be
      vulnerable for breeding purposes. A complicated allelic or linkage relationship
      between the identified genes is discussed. The results of the study will be
      useful for breeding for durable resistance by creating polygenic complexes.

PMID- 24906008
TI  - Reovirus-mediated induction of ADAR1 (p150) minimally alters RNA editing patterns
      in discrete brain regions.
AB  - Transcripts encoding ADAR1, a double-stranded, RNA-specific adenosine deaminase
      involved in the adenosine-to-inosine (A-to-I) editing of mammalian RNAs, can be
      alternatively spliced to produce an interferon-inducible protein isoform (p150)
      that is up-regulated in both cell culture and in vivo model systems in response
      to pathogen or interferon stimulation. In contrast to other tissues, p150 is
      expressed at extremely low levels in the brain and it is unclear what role, if
      any, this isoform may play in the innate immune response of the central nervous
      system (CNS) or whether the extent of editing for RNA substrates critical for CNS
      function is affected by its induction. To investigate the expression of ADAR1
      isoforms in response to viral infection and subsequent alterations in A-to-I
      editing profiles for endogenous ADAR targets, we used a neurotropic strain of
      reovirus to infect neonatal mice and quantify A-to-I editing in discrete brain
      regions using a multiplexed, high-throughput sequencing strategy. While
      intracranial injection of reovirus resulted in a widespread increase in the
      expression of ADAR1 (p150) in multiple brain regions and peripheral organs,
      significant changes in site-specific A-to-I conversion were quite limited,
      suggesting that steady-state levels of p150 expression are not a primary
      determinant for modulating the extent of editing for numerous ADAR targets in
      vivo.

PMID- 24906011
TI  - Integrin-linked kinase regulates endothelial cell nitric oxide synthase
      expression in hepatic sinusoidal endothelial cells.
AB  - BACKGROUND & AIMS: Portal hypertension results from endothelial dysfunction after
      liver injury caused in part by abnormal production of endothelial cell derived
      nitric oxide synthase (eNOS). Here, we have postulated that endothelial
      mechanosensing pathways involving integrin-linked kinase (ILK) may play a
      critical role in portal hypertension, eNOS expression and function. In this
      study, we investigated the role of ILK and the small GTP-binding protein, Rho, in
      sinusoidal endothelial cell (SEC) eNOS regulation and function. METHODS: Primary
      liver SECs were isolated using standard techniques. Liver injury was induced by
      performing bile duct ligation (BDL). To examine the expression of Rho and ILK in
      vivo during wound healing, SECs were infected with constitutively active Rho
      (V14), a dominant negative Rho (N19) and constructs encoding ILK and a short
      hairpin-inhibiting ILK. RESULTS: Integrin-linked kinase expression was increased
      in SECs after liver injury; endothelin-1, vascular endothelial growth factor, and
      transforming growth factor beta-1 stimulated ILK expression in SECs. ILK
      expression in turn led to eNOS upregulation and to enhance eNOS phosphorylation
      and NO production. ILK knockdown or ILK (kinase) inhibition reduced eNOS mRNA
      expression, promoter activity, eNOS expression and ultimately NO production. In
      contrast, ILK overexpression had the opposite effect. Inhibition of ILK activity
      also disrupted the actin cytoskeleton in isolated SECs. Rho overexpression
      suppressed phosphorylation of the serine-threonine kinase, Akt and inhibited eNOS
      phosphorylation. Finally, inhibition of Rho function with the RGS domain of the
      p115-Rho-specific GEF (p115-RGS) significantly increased eNOS phosphorylation.
      CONCLUSIONS: Our data suggest a potential role for ILK, the cytoskeleton and ILK
      signalling partners including Rho in regulating intrahepatic SEC eNOS expression
      and function.

PMID- 24906012
TI  - 2-year-old girl with pancytopenia due to vitamin B12 (cobalamin) deficiency.

PMID- 24906015
TI  - Analysing Deviation-From-Target Data: Applying the Correct Force in Sellick's
      Maneuver.
AB  - The problem of comparing the deviation from a target of two or more treatments or
      procedures arises now and again in medicine. Practitioners usually carry out a t
      test on a loss function such as absolute error. We have adapted and developed
      statistical methods to give a normative methodology for deviation-from-target
      problems and exemplify them by evaluating the performance of a tactile feedback
      device. Parametric and nonparametric analyses are compared and contrasted. We
      recommend nonparametric methods for inference about loss functions such as
      absolute error, with a permutation test for testing the hypothesis that the two
      methods perform identically, and the nonparametric bootstrap for deriving
      standard errors and confidence intervals on loss function ratios. We develop a
      new permutation test that can be used when the practitioner is unwilling to
      decide which loss function should be used. We recommend parametric analysis when
      more insight into how one method is superior is desired, or there are covariates,
      and discuss the complications. The results for our example are that the tactile
      sensing device reduces an upward bias in applied force, and more importantly
      reduces the spread (variance) of the applied force. It performs significantly
      better than manual force application. 

PMID- 24906014
TI  - Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic
      review and meta-analysis.
AB  - PURPOSE: Tumor-associated neutrophils (TAN) have been reported in a variety of
      malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic
      role of TAN in cancer. METHOD: Pubmed, Embase and web of science databases were
      searched for studies published up to April 2013. Pooled hazard ratios (HRs) and
      their corresponding 95% confidence intervals (CIs) were calculated. The impact of
      neutrophils localization and primary antibody were also assessed. RESULTS: A
      total of 3946 patients with various solid tumors from 20 studies were included.
      High density of intratumoral neutrophils were independently associated with
      unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36-2.07, I2 = 55.8%,
      p<0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36
      (95%CI: 2.08-5.42, I2 = 0%, p<0.001) for cancer-specific survival (CSS) and 1.66
      (95%CI: 1.37-2.01, I2 = 70.5%, p<0.001) for overall survival (OS). Peritumoral
      and stromal neutrophils were not statistically significantly associated with
      survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47
      2.22, I2 = 67.7%, p<0.001) for CD66b, and 1.44 (95%CI: 0.90-2.30, I2 = 45.9%, p =
      0.125) for CD15, suggesting that CD66b positive TAN might have a better
      prognostic value than CD15. CONCLUSION: High levels of intratumoral neutrophils
      are associated with unfavorable recurrence-free, cancer-specific and overall
      survival.

PMID- 24906013
TI  - Prescribing pattern of anti-Parkinson drugs in Japan: a trend analysis from 2005
      to 2010.
AB  - OBJECTIVE: Therapeutic options for Parkinson's disease mainly consist of L-dopa
      and dopamine agonists. However, in Japan, the product labeling of the ergot
      dopamine agonists, cabergoline and pergolide, was revised in April 2007 due to
      the risk of developing cardiac valvulopathy. Here, we describe the prescribing
      trends of anti-Parkinson drugs from 2005 through 2010 in Japan, and examined
      whether these trends changed after the drug safety measures in 2007. METHODS AND
      PATIENTS: We used medical claim data from January 2005 to December 2010 for
      Parkinson's disease patients older than 30 years who were prescribed anti
      Parkinson drugs. We calculated the proportion of patients prescribed each drug
      for each year, and compared the proportions of first-line drugs prescribed before
      and after April 2007. We also examined the prescription variations of
      cabergoline/pergolide users one year before or after April 2007. RESULTS: L-dopa
      was the most frequently prescribed drug for Parkinson's disease (2005, 58%; 2010,
      51%). The proportion of patients prescribed ergot dopamine agonists markedly
      decreased and non-ergot dopamine agonists increased after 2007. Among first-line
      drugs, the proportion of non-ergot agents increased after April 2007. Among 54
      cabergoline/pergolide users, 24 (44%) discontinued these drugs, nine of whom
      switched to non-ergot agents. CONCLUSION: L-dopa was the mainstay of Parkinson's
      disease treatment between 2005 and 2010 in Japan. There was a decrease in ergot
      agents and an increase in non-ergot agents prescribed after the regulatory
      actions in 2007.

PMID- 24906016
TI  - Can marine bacteria be recruited from freshwater sources and the air?
AB  - There is now clear evidence that microorganisms present biogeographic patterns,
      yet the processes that create and maintain them are still not well understood. In
      particular, the contribution of dispersal and its exact impact on local community
      composition is still unclear. For example, dispersing cells may not thrive in
      recipient environments, but may still remain part of the local species pool.
      Here, we experimentally tested if marine bacteria can be retrieved from
      freshwater communities (pelagic and sediment) and the atmosphere by exposing
      bacteria from three lakes, that differ in their proximity to the Norwegian Sea,
      to marine conditions. We found that the percentage of freshwater taxa decreased
      with increasing salinities, whereas marine taxa increased along the same
      gradient. Our results further showed that this increase was stronger for lake and
      sediment compared with air communities. Further, significant increases in the
      average niche breadth of taxa were found for all sources, and in particular lake
      water and sediment communities, at higher salinities. Our results therefore
      suggests that marine taxa can readily grow from freshwater sources, but that the
      response was likely driven by the growth of habitat generalists that are
      typically found in marine systems. Finally, there was a greater proportion of
      marine taxa found in communities originating from the lake closest to the
      Norwegian Sea. In summary, this study shows that the interplay between bacterial
      dispersal limitation and dispersal from internal and external sources may have an
      important role for community recovery in response to environmental change.

PMID- 24906018
TI  - FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene
      discovery project.
AB  - Inherited monogenic disease has an enormous impact on the well-being of children
      and their families. Over half of the children living with one of these conditions
      are without a molecular diagnosis because of the rarity of the disease, the
      marked clinical heterogeneity, and the reality that there are thousands of rare
      diseases for which causative mutations have yet to be identified. It is in this
      context that in 2010 a Canadian consortium was formed to rapidly identify
      mutations causing a wide spectrum of pediatric-onset rare diseases by using whole
      exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium
      brought together clinicians and scientists from 21 genetics centers and three
      science and technology innovation centers from across Canada. From nation-wide
      requests for proposals, 264 disorders were selected for study from the 371
      submitted; disease-causing variants (including in 67 genes not previously
      associated with human disease; 41 of these have been genetically or functionally
      validated, and 26 are currently under study) were identified for 146 disorders
      over a 2-year period. Here, we present our experience with four strategies
      employed for gene discovery and discuss FORGE's impact in a number of realms,
      from clinical diagnostics to the broadening of the phenotypic spectrum of many
      diseases to the biological insight gained into both disease states and normal
      human development. Lastly, on the basis of this experience, we discuss the way
      forward for rare-disease genetic discovery both in Canada and internationally. 

PMID- 24906017
TI  - Distinct signatures of host-microbial meta-metabolome and gut microbiome in two
      C57BL/6 strains under high-fat diet.
AB  - A combinatory approach using metabolomics and gut microbiome analysis techniques
      was performed to unravel the nature and specificity of metabolic profiles related
      to gut ecology in obesity. This study focused on gut and liver metabolomics of
      two different mouse strains, the C57BL/6J (C57J) and the C57BL/6N (C57N) fed with
      high-fat diet (HFD) for 3 weeks, causing diet-induced obesity in C57N, but not in
      C57J mice. Furthermore, a 16S-ribosomal RNA comparative sequence analysis using
      454 pyrosequencing detected significant differences between the microbiome of the
      two strains on phylum level for Firmicutes, Deferribacteres and Proteobacteria
      that propose an essential role of the microbiome in obesity susceptibility. Gut
      microbial and liver metabolomics were followed by a combinatory approach using
      Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and ultra
      performance liquid chromatography time of tlight MS/MS with subsequent
      multivariate statistical analysis, revealing distinctive host and microbial
      metabolome patterns between the C57J and the C57N strain. Many taurine-conjugated
      bile acids (TBAs) were significantly elevated in the cecum and decreased in liver
      samples from the C57J phenotype likely displaying different energy utilization
      behavior by the bacterial community and the host. Furthermore, several metabolite
      groups could specifically be associated with the C57N phenotype involving fatty
      acids, eicosanoids and urobilinoids. The mass differences based metabolite
      network approach enabled to extend the range of known metabolites to important
      bile acids (BAs) and novel taurine conjugates specific for both strains. In
      summary, our study showed clear alterations of the metabolome in the
      gastrointestinal tract and liver within a HFD-induced obesity mouse model in
      relation to the host-microbial nutritional adaptation.

PMID- 24906019
TI  - Transcriptional consequences of 16p11.2 deletion and duplication in mouse cortex
      and multiplex autism families.
AB  - Reciprocal copy-number variation (CNV) of a 593 kb region of 16p11.2 is a common
      genetic cause of autism spectrum disorder (ASD), yet it is not completely
      penetrant and can manifest in a wide array of phenotypes. To explore its
      molecular consequences, we performed RNA sequencing of cerebral cortex from mouse
      models with CNV of the syntenic 7qF3 region and lymphoblast lines from 34 members
      of 7 multiplex ASD-affected families harboring the 16p11.2 CNV. Expression of all
      genes in the CNV region correlated well with their DNA copy number, with no
      evidence of dosage compensation. We observed effects on gene expression outside
      the CNV region, including apparent positional effects in cis and in trans at
      genomic segments with evidence of physical interaction in Hi-C chromosome
      conformation data. One of the most significant positional effects was telomeric
      to the 16p11.2 CNV and includes the previously described "distal" 16p11.2
      microdeletion. Overall, 16p11.2 CNV was associated with altered expression of
      genes and networks that converge on multiple hypotheses of ASD pathogenesis,
      including synaptic function (e.g., NRXN1, NRXN3), chromatin modification (e.g.,
      CHD8, EHMT1, MECP2), transcriptional regulation (e.g., TCF4, SATB2), and
      intellectual disability (e.g., FMR1, CEP290). However, there were differences
      between tissues and species, with the strongest effects being consistently within
      the CNV region itself. Our analyses suggest that through a combination of
      indirect regulatory effects and direct effects on nuclear architecture,
      alteration of 16p11.2 genes disrupts expression networks that involve other genes
      and pathways known to contribute to ASD, suggesting an overlap in mechanisms of
      pathogenesis. 

PMID- 24906021
TI  - The importance of large-amplitude motions for the interpretation of mid-infrared
      vibrational absorption and circular dichroism spectra: 6,6'-dibromo-[1,1'
      binaphthalene]-2,2'-diol in dimethyl sulfoxide.
AB  - Using the 6,6'-dibromo-[1,1'-binaphthalene]-2,2'-diol molecule and its
      vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra
      measured in deuterated dimethyl sulfoxide as example, we present a first detailed
      study of the effects induced in VCD spectra by the large-amplitude motions of
      solvent molecules loosely bound to a solute molecule. We show that this type of
      perturbation can induce significant effects in the VA and VCD spectra. We also
      outline a computational procedure that can effectively model the effects induced
      in the spectra and at the same time provide detailed structural information
      regarding the relative orientations of moieties involved in a solute-solvent
      molecular complex. 

PMID- 24906022
TI  - Expression of Arabidopsis acyl-CoA-binding proteins AtACBP1 and AtACBP4 confers
      Pb(II) accumulation in Brassica juncea roots.
AB  - In Arabidopsis thaliana, the expression of two genes encoding acyl-CoA-binding
      proteins (ACBPs) AtACBP1 and AtACBP4, were observed to be induced by lead
      [Pb(II)] in shoots and roots in qRT-PCR analyses. Quantitative GUS (beta
      glucuronidase) activity assays confirmed induction of AtACBP1pro::GUS by Pb(II).
      Electrophoretic mobility shift assays (EMSAs) revealed that Pas elements in the
      5'-flanking region of AtACBP1 were responsive to Pb(II) treatment. AtACBP1 and
      AtACBP4 were further compared in Pb(II) uptake using Brassica juncea, a potential
      candidate for phytoremediation given its rapid growth, large roots, high biomass
      and good capacity to accumulate heavy metals. Results from atomic absorption
      analyses on transgenic B. juncea expressing AtACBP1 or AtACBP4 indicated Pb(II)
      accumulation in roots. Subsequent Pb(II)-tracing assays demonstrated Pb(II)
      accumulation in the cytosol of root tips and vascular tissues of transgenic B.
      juncea AtACBP1-overexpressors (OXs) and AtACBP4-OXs and transgenic Arabidopsis
      AtACBP1-OXs. Transgenic Arabidopsis AtACBP1-OXs sequestered Pb(II) in the
      trichomes and displayed tolerance to hydrogen peroxide (H2 O2 ) treatment. In
      addition, AtACBP1 and AtACBP4 were H2 O2 -induced in the roots of wild-type
      Arabidopsis, while lipid hydroperoxide (LOOH) measurements of B. juncea AtACBP1
      OX and AtACBP4-OX roots suggested that AtACBP1 and AtACBP4 can protect lipids
      against Pb(II)-induced lipid peroxidation. 

PMID- 24906020
TI  - Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye
      malformations.
AB  - We identified four different missense mutations in the single-exon gene MAB21L2
      in eight individuals with bilateral eye malformations from five unrelated
      families via three independent exome sequencing projects. Three mutational events
      altered the same amino acid (Arg51), and two were identical de novo mutations
      (c.151C>T [p.Arg51Cys]) in unrelated children with bilateral anophthalmia,
      intellectual disability, and rhizomelic skeletal dysplasia. c.152G>A (p.Arg51His)
      segregated with autosomal-dominant bilateral colobomatous microphthalmia in a
      large multiplex family. The fourth heterozygous mutation (c.145G>A [p.Glu49Lys])
      affected an amino acid within two residues of Arg51 in an adult male with
      bilateral colobomata. In a fifth family, a homozygous mutation (c.740G>A
      [p.Arg247Gln]) altering a different region of the protein was identified in two
      male siblings with bilateral retinal colobomata. In mouse embryos, Mab21l2 showed
      strong expression in the developing eye, pharyngeal arches, and limb bud. As
      predicted by structural homology, wild-type MAB21L2 bound single-stranded RNA,
      whereas this activity was lost in all altered forms of the protein. MAB21L2 had
      no detectable nucleotidyltransferase activity in vitro, and its function remains
      unknown. Induced expression of wild-type MAB21L2 in human embryonic kidney 293
      cells increased phospho-ERK (pERK1/2) signaling. Compared to the wild-type and
      p.Arg247Gln proteins, the proteins with the Glu49 and Arg51 variants had
      increased stability. Abnormal persistence of pERK1/2 signaling in MAB21L2
      expressing cells during development is a plausible pathogenic mechanism for the
      heterozygous mutations. The phenotype associated with the homozygous mutation
      might be a consequence of complete loss of MAB21L2 RNA binding, although the
      cellular function of this interaction remains unknown. 

PMID- 24906023
TI  - Large-scale protein analysis of European beech trees following four vegetation
      periods of twice ambient ozone exposure.
AB  - In the present study, we performed a large-scale protein analysis based on 2-DE
      DIGE to examine the effects of ozone on the leaves of juvenile European beech
      (Fagus sylvatica L.), one of the most important deciduous tree species in Central
      Europe. To this end, beech trees were grown under field conditions and subjected
      to ambient and twice ambient ozone concentrations during the vegetation periods
      of four consecutive years. The twice ambient ozone concentration altered the
      abundance of 237 protein spots, which showed relative ratios higher than 30%
      compared to the ambient control trees. A total of 74 protein spots were subjected
      to mass spectrometry identification (LC-MS/MS), followed by homology-driven
      searches. The differentially expressed proteins participate in key biological
      processes including the Calvin cycle and photosynthesis, carbon metabolism,
      defense- and stress-related responses, detoxification mechanisms, protein folding
      and degradation, and mechanisms involved in senescence. The ozone-induced
      responses provide evidence of a changing carbon metabolism and counteraction
      against increased levels of reactive oxygen species. BIOLOGICAL SIGNIFICANCE:
      This study provides useful information on how European beech, an economically and
      ecologically important tree species, reacts on the molecular level to increased
      ozone concentrations expected in the near future. The main emphasis in the
      present study was placed on identifying differentially abundant proteins after
      long-term ozone exposure under climatically realistic settings, rather than short
      term responses or reactions under laboratory conditions. Additionally, using
      nursery-grown beech trees, we took into account the natural genotypic variation
      of this species. As such, the results presented here provide information on
      molecular responses to ozone in an experimental plant system at very close to
      natural conditions. Furthermore, this proteomic approach was supported by
      previous studies on the present experiment. Ultimately, the combination of this
      proteomic approach with several approaches including transcriptomics, analysis of
      non-structural carbohydrates, and morphological effects contributes to a more
      global picture of how beech trees react under increased ozone concentrations.

PMID- 24906024
TI  - Brassica napus seed endosperm - metabolism and signaling in a dead end tissue.
AB  - Oilseeds are an important element of human nutrition and of increasing
      significance for the production of industrial materials. The development of the
      seeds is based on a coordinated interplay of the embryo and its surrounding
      tissue, the endosperm. This study aims to give insights into the physiological
      role of endosperm for seed development in the oilseed crop Brassica napus. Using
      protein separation by two-dimensional (2D) isoelectric focusing (IEF)/SDS
      polyacrylamide gel electrophoresis (PAGE) and protein identification by mass
      spectrometry three proteome projects were carried out: (i) establishment of an
      endosperm proteome reference map, (ii) proteomic characterization of endosperm
      development and (iii) comparison of endosperm and embryo proteomes. The endosperm
      proteome reference map comprises 930 distinct proteins, including enzymes
      involved in genetic information processing, carbohydrate metabolism,
      environmental information processing, energy metabolism, cellular processes and
      amino acid metabolism. To investigate dynamic changes in protein abundance during
      seed development, total soluble proteins were extracted from embryo and endosperm
      fractions at defined time points. Proteins involved in sugar converting and
      recycling processes, ascorbate metabolism, amino acid biosynthesis and redox
      balancing were found to be of special importance for seed development in B.
      napus. Implications for the seed filling process and the function of the
      endosperm for seed development are discussed. BIOLOGICAL SIGNIFICANCE: The
      endosperm is of key importance for embryo development during seed formation in
      plants. We present a broad study for characterizing endosperm proteins in the
      oilseed plant B. napus. Furthermore, a project on the biochemical interplay
      between the embryo and the endosperm during seed development is presented. We
      provide evidence that the endosperm includes a complete set of enzymes necessary
      for plant primary metabolism. Combination of our results with metabolome data
      will further improve systems-level understanding of the seed filling process and
      provide rational strategies for plant bioengineering.

PMID- 24906025
TI  - Speciation analysis for trace levels of selenoproteins in cultured human cells.
AB  - A semi-quantitative method was developed for the non-targeted detection of trace
      levels of human selenoproteins in cytoplasmic cell extracts without the use of
      radioactive isotopes. The method was based on the direct detection of
      selenoproteins in iso-electrofocusing (IEF) electrophoretic strips by laser
      ablation-inductively coupled plasma mass spectrometry (LA-ICP MS). The proteins
      were identified in the non-ablated parts of the gel corresponding to the LA-ICP
      MS peak apexes by electrospray Orbitrap MS/MS. The method allowed a high
      resolution of the selenoproteins (peak width 0.06pH unit) using 3-10 pI strips.
      The protein detection limits were down to 1ngmL(-1) (as Se). The method was
      applied to the selenoprotein speciation in different human cell lines: Hek293
      (kidney), HepG2 (liver), HaCaT (skin) and LNCaP (prostate). The principal
      proteins found included Selenoprotein 15 (Sep15), Glutathione peroxidase 1 (GPx1)
      and Glutathione peroxidase 4 (GPx4) and Thioredoxin reductase 1 (TRxR1) and
      Thioredoxin reductase 2 (TRxR2). BIOLOGICAL SIGNIFICANCE: Our paper presents the
      development of a semi-quantitative method for the non-targeted detection of trace
      levels of human selenoproteins in cytoplasmic cell extracts; it offers a first
      comprehensive screening of the entire biological selenoproteomes expressed in
      cell lines without the use of radioactive (75)Se. The method was based on the
      direct detection of selenoproteins in iso-electrofocusing (IEF) electrophoretic
      strips by laser ablation-inductively coupled plasma mass spectrometry (LA-ICP
      MS). The proteins were identified in the non-ablated parts of the gel
      corresponding to the LA-ICP MS peak apexes by electrospray Orbitrap MS/MS. The
      method allowed a high resolution of the selenoproteins (peak width 0.06pH unit)
      using 3-10 pI strips. The protein detection limits were down to 1ngmL(-1) (as
      Se); by far the lowest ever reported. The method was applied to the selenoprotein
      speciation in different human cell lines: Hek293 (kidney), HepG2 (liver), HaCaT
      (skin) and LNCaP (prostate). The principal proteins found included Selenoprotein
      15 (Sep15), Glutathione peroxidase 1 (GPx1) and Glutathione peroxidase 4 (GPx4)
      and Thioredoxin reductase 1 (TRxR1) and Thioredoxin reductase 2 (TRxR2). The IEF
      LA-ICPMS indicates the presence of multiple forms of some selenoproteins which
      are for the moment impossible to distinguish because of the similarity of the
      bottom-up, proteomics data sets.

PMID- 24906026
TI  - Within- and across-breed imputation of high-density genotypes in dairy and beef
      cattle from medium- and low-density genotypes.
AB  - The objective of this study was to evaluate, using three different genotype
      density panels, the accuracy of imputation from lower- to higher-density
      genotypes in dairy and beef cattle. High-density genotypes consisting of 777,962
      single-nucleotide polymorphisms (SNP) were available on 3122 animals comprised of
      269, 196, 710, 234, 719, 730 and 264 Angus, Belgian Blue, Charolais, Hereford,
      Holstein-Friesian, Limousin and Simmental bulls, respectively. Three different
      genotype densities were generated: low density (LD; 6501 autosomal SNPs), medium
      density (50K; 47,770 autosomal SNPs) and high density (HD; 735,151 autosomal
      SNPs). Imputation from lower- to higher-density genotype platforms was undertaken
      within and across breeds exploiting population-wide linkage disequilibrium. The
      mean allele concordance rate per breed from LD to HD when undertaken using a
      single breed or multiple breed reference population varied from 0.956 to 0.974
      and from 0.947 to 0.967, respectively. The mean allele concordance rate per breed
      from 50K to HD when undertaken using a single breed or multiple breed reference
      population varied from 0.987 to 0.994 and from 0.987 to 0.993, respectively. The
      accuracy of imputation was generally greater when the reference population was
      solely comprised of the breed to be imputed compared to when the reference
      population comprised of multiple breeds, although the impact was less when
      imputing from 50K to HD compared to imputing from LD.

PMID- 24906028
TI  - Application of supernodal sparse factorization and inversion to the estimation of
      (co)variance components by residual maximum likelihood.
AB  - We demonstrated that supernodal techniques were more efficient than traditional
      methods for factorization and inversion of a coefficient matrix of mixed model
      equations (MME), which are often required in residual maximum likelihood (REML).
      Supernodal left-looking and inverse multifrontal algorithms were employed for
      sparse factorization and inversion, respectively. The approximate minimum degree
      or multilevel nested dissection was used for ordering. A new computer package,
      Yet Another MME Solver (YAMS), was developed and compared with FSPAK with respect
      to computing time and size of temporary memory for 13 test matrices. The matrices
      were produced by fitting animal models to dairy data and by using simulations
      from sire, sire-maternal grand sire, maternal and dominance models for phenotypic
      data and animal model for genomic data. The order of matrices ranged from 32,840
      to 1,048,872. The YAMS software factorized and inverted the matrices up to 13 and
      10 times faster than FSPAK, respectively, when an appropriate ordering strategy
      was applied. The YAMS package required at most 282 MB and 512 MB of temporary
      memory for factorization and inversion, respectively. Processing time per
      iteration in average information REML was reduced, using YAMS. The YAMS package
      is freely available on request by contacting the corresponding author.

PMID- 24906027
TI  - Genome-wide association study for feedlot average daily gain in Nellore cattle
      (Bos indicus).
AB  - The genome-wide association study (GWAS) results are presented for average daily
      gain (ADG) in Nellore cattle. Phenotype of 720 male Bos indicus animals with
      information of ADG in feedlots and 354,147 single-nucleotide polymorphisms (SNPs)
      obtained from a database added by information from Illumina Bovine HD (777,962
      SNPs) and Illumina BovineSNP50 (54,609) by imputation were used. After quality
      control and imputation, 290,620 SNPs remained in the association analysis, using
      R package Genome-wide Rapid Association using Mixed Model and Regression method
      GRAMMAR-Gamma. A genomic region with six significant SNPs, at Bonferroni
      corrected significance, was found on chromosome 3. The most significant SNP
      (rs42518459, BTA3: 85849977, p = 9.49 * 10(-8)) explained 5.62% of the phenotypic
      variance and had the allele substitution effect of -0.269 kg/day. Important genes
      such as PDE4B, LEPR, CYP2J2 and FGGY are located near this region, which is
      overlapped by 12 quantitative trait locus (QTLs) described for several production
      traits. Other regions with markers with suggestive effects were identified in
      BTA6 and BTA10. This study showed regions with major effects on ADG in Bos
      indicus in feedlots. This information may be useful to increase the efficiency of
      selecting this trait and to understand the physiological processes involved in
      its regulation.

PMID- 24906030
TI  - High-energy redox-flow batteries with hybrid metal foam electrodes.
AB  - A nonaqueous redox-flow battery employing [Co(bpy)3](+/2+) and [Fe(bpy)3](2+/3+)
      redox couples is proposed for use in large-scale energy-storage applications. We
      successfully demonstrate a redox-flow battery with a practical operating voltage
      of over 2.1 V and an energy efficiency of 85% through a rational cell design. By
      utilizing carbon-coated Ni-FeCrAl and Cu metal foam electrodes, the
      electrochemical reactivity and stability of the nonaqueous redox-flow battery can
      be considerably enhanced. Our approach intoduces a more efficient conversion of
      chemical energy into electrical energy and enhances long-term cell durability.
      The cell exhibits an outstanding cyclic performance of more than 300 cycles
      without any significant loss of energy efficiency. Considering the increasing
      demands for efficient energy storage, our achievement provides insight into a
      possible development pathway for nonaqueous redox-flow batteries with high energy
      densities. 

PMID- 24906029
TI  - Randomized, double blinded, placebo-controlled trial to evaluate the efficacy and
      safety of tolvaptan in Chinese patients with hyponatremia caused by SIADH.
AB  - To study the effect of tolvaptan on non-acute, non-hypovolemic hyponatremia in
      inappropriate secretion of antidiuretic hormone (SIADH) syndrome in Chinese
      patients. Hyponatremic SIADH patients received placebo (N = 18) or tolvaptan (N =
      19) at an initial dose of 15 mg/day with further titration to 30 mg/day and 60
      mg/day based on serum sodium concentrations. Randomized, double-blind, placebo
      controlled trial. Primary endpoint was the change of the serum sodium from
      baseline to days 4 and 7. Analysis of covariance (ANCOVA) was used for
      statistical analysis. At day 4, average daily changes in serum sodium levels from
      baseline was 1.9 +/- 2.9 mmol/L (1.9 +/- 2.9 mEq/L) in the placebo group and 8.1
      +/- 3.6 mmol/L (8.1 +/- 3.6 mEq/L) in the tolvaptan group; at day 7, the values
      were 2.5 +/- 3.9 mmol/L (2.5 +/- 3.9 mEq/L) and 8.6 +/- 3.9 mmol/L (8.6 +/- 3.9
      mmEq/L) for the placebo and tolvaptan groups (ANCOVA, P < 0.001). At days 4 and
      7, daily urine output and proportions of patients with normalized serum sodium
      were significantly superior in the tolvaptan group. The most common adverse
      events occurring in the tolvaptan group were dry mouth and thirst. Tolvaptan
      demonstrated superiority to placebo in the treatment of Chinese SIADH patients
      with hyponatremia by elevating serum sodium concentration with acceptable safety
      profile. 

PMID- 24906031
TI  - Ceric ammonium nitrate (CAN) catalyzed modification of ketones via two C-C bond
      cleavages with the retention of the oxo-group.
AB  - A simple ceric ammonium nitrate (CAN) catalyzed functionalization of ketones
      through double C-C bond cleavage strategy has been disclosed. This reaction
      provides a mild, practical method toward carbamoyl azides, which are versatile
      intermediates and building blocks in organic synthesis. Based on relevant
      mechanistic studies, a unique and plausible C-C bond and N-O bond cleavage
      process is proposed, where the oxyamination intermediate plays an important role
      in this reaction. 

PMID- 24906032
TI  - Trajectories and predictors of nocturnal awakenings and sleep duration in
      infants.
AB  - OBJECTIVES: To examine the trajectories of sleep duration and nocturnal
      awakenings in infants from 6 to 18 months of age and to identify predictors of
      short sleep duration and nocturnal awakenings. METHODS: Data for this study come
      from the Norwegian Mother and Child Cohort Study conducted at the Norwegian
      Institute of Public Health. A total of 55,831 mother reports of child sleep were
      used to estimate the stability and predictors of awakenings and short sleep.
      RESULTS: Nocturnal awakenings were frequent among 6-month-old children. Although
      there was an overall reduction in both sleep duration and nocturnal awakenings
      from 6 to 18 months, the chronicity of sleep problems was high and impacted by
      prior sleep behavior and sleeping arrangements. Bedsharing was an independent and
      graded predictor of nocturnal awakenings and short sleep duration, also after
      controlling for prior sleep. Breastfeeding was related to concurrent nocturnal
      awakening but was not negatively related to later nocturnal awakenings.
      CONCLUSIONS: Considering the chronicity of nocturnal awakening and its
      association with bedsharing, our findings support current recommendations of
      reducing bedsharing to improve sleep among infants.

PMID- 24906033
TI  - A national profile of Tourette syndrome, 2011-2012.
AB  - OBJECTIVE: To provide recent estimates of the prevalence of Tourette syndrome
      among a nationally representative sample of US children and to describe the
      association of Tourette syndrome with indicators of health and functioning.
      METHODS: Data on 65,540 US children aged 6 to 17 years from the 2011-2012
      National Survey of Children's Health were analyzed. Parents reported whether a
      health care provider had ever told them their child had Tourette syndrome or
      other neurobehavioral or chronic health conditions and whether their child had
      current Tourette syndrome. RESULTS: Based on parents' report, 0.19% of US
      children had Tourette syndrome; the average age of diagnosis was 8.1 years.
      Children with Tourette syndrome, compared with those without, were more likely to
      have co-occurring neurobehavioral and other health conditions, meet criteria for
      designation as having a special health care need, receive mental health
      treatment, have unmet mental health care needs, and have parents with high
      parenting aggravation and parents who were contacted about school problems; they
      were less likely to receive effective care coordination or have a medical home.
      After controlling for co-occurring neurobehavioral conditions, the findings on
      parents being contacted about school problems and children having unmet mental
      health care needs were no longer significant. CONCLUSIONS: Tourette syndrome is
      characterized by co-occurring neurobehavioral and other health conditions, and
      poorer health, education, and family relationships. The findings support previous
      recommendations to consider co-occurring conditions in the diagnosis and
      treatment of Tourette syndrome. Future research may explore whether having a
      medical home improves outcomes among children with Tourette syndrome.

PMID- 24906034
TI  - Executive function mediates effects of gestational age on functional outcomes and
      behavior in preschoolers.
AB  - OBJECTIVE: To investigate the role of executive function (EF) skills, measured by
      parent-rating and performance-based instruments, as mediators of the effects of
      gestational age (GA) on functional outcomes and behavior symptoms in preterm (PT)
      and full-term (FT) preschoolers. PATIENTS AND METHODS: Children born PT (n = 70;
      mean GA, 29.6 weeks; mean birth weight, 1365 g) were compared to children born FT
      (n = 79) on composite measures of EF (using the Behavior Rating Inventory of
      Executive Function and a performance-based EF battery), adaptive function,
      prereading skills, and behavior symptoms. For the entire sample, mediation
      analyses examined the effect of GA on the outcomes with EF as mediator. RESULTS:
      Compared to children born FT, children born PT had significantly higher parent
      rated EF scores and lower performance-based EF scores, both indicating more
      problems; furthermore, children born PT had lower adaptive function and
      prereading scores and more problematic behavior. GA contributed to adaptive
      function, prereading skills, and behavior symptoms for all children. EF acted as
      a mediator of GA for all 3 outcomes; different patterns emerged for parent-rated
      and performance-based EF evaluations. For adaptive function, both EF measures
      significantly mediated the effects of GA; for prereading skills, only performance
      based EF was significant; for behavior symptoms, only parent-rated EF was
      significant. CONCLUSIONS: We propose standard assessment of EF, using both parent
      rating and performance-based EF measures, in young PT children and other children
      at the risk of EF impairments. EF skills are measurable, mediate important
      functional outcomes, and may serve as intervention targets.

PMID- 24906036
TI  - Attention deficit hyperactivity, fetal alcohol spectrum disorder, or something
      else: the broad differential of kindergarten suspension.
AB  - CASE: Thomas is a 5-year 6-month-old boy whose parents requested an urgent care
      appointment because he has recently been suspended from kindergarten stating "and
      his doctor must see him before he can come back." His suspension from
      kindergarten was due to kicking and biting his classmates, but he has also become
      increasingly aggressive at home. His teacher reported that he has always had a
      high activity level and difficulty shifting attention between tasks, as well as
      noncompliance with rules and directions. He is noted to have learning challenges
      and is showing difficulties in the concept of numbers and letter sounds. The
      practice has followed Thomas since his healthy birth. He has a history of delayed
      language development, and he received early intervention services from 2 years of
      age. He spoke his first word at 2 years 6 months. He started a half-day preschool
      program at 3 years of age. He had difficulty acclimating to preschool,
      interacting with peers, and was described as "hyperactive" by his teachers. His
      program was modified to decrease his time having to sit in a circle time, and he
      often required the support of the paraprofessional in the classroom. His parents
      have always described him as a "difficult child." He gets frustrated easily and
      can tantrum for up to 2 hours multiple times in a week when his immediate needs
      or requests are not met. He has difficulty falling asleep, has frequent night
      awakenings, and often has trouble getting back to sleep. His self-help skills are
      poor, and he has difficulty with activities such as brushing his teeth and
      dressing. His parents report that he does not seem to remember rules from day to
      day. He was evaluated at 5 years of age and diagnosed with Attention Deficit
      Hyperactivity Disorder, but his response to stimulants has been limited. Thomas
      is an only child. His parents are college educated and professionally employed.
      They deny drug use, domestic violence, and guns in the home. They reported that
      prior to the pregnancy, they enjoyed "partying" with friends on the weekends, but
      Thomas's mother reported that she stopped drinking as soon as she realized she
      was pregnant. All are wondering whether this child might have a fetal alcohol
      spectrum disorder, although he seems to have no clear facial dysmorphology. It is
      unsure what the next step might be and if there is value added in pursuing this
      diagnosis. What do you do next?

PMID- 24906035
TI  - Mental health screening and consultation in primary care: The role of child age
      and parental concerns [corrected].
AB  - OBJECTIVE: To determine (1) how child age relates to parent concerns about child
      behavior and (2) how child age and parent concerns correlate with provider
      referrals and family attendance at mental health consultant (MHC) appointments.
      METHODS: Data were obtained from Rhode Island's Project, Linking Actions for
      Unmet Needs in Children's Health, in which universal developmental and behavioral
      screening and MHCs were embedded within primary care sites serving low-income
      diverse families. Children 9 months to 8 years of age were eligible for the study
      if they had a scheduled screening well-child visit in 2010 (N = 1451). Families
      completing screening and/or those referred for a MHC appointment were included in
      analyses (n = 700). Outcome measures included parent-reported concerns about
      child behavior, referral status following screening, and family attendance at the
      MHC appointment. RESULTS: For every 1-month increase in child age, there was a
      1.02 times increase in the likelihood of parent behavioral concern and a 1.04
      times increase in the likelihood of mental health referral, even when controlling
      for child behavior. MHC-referred children older than 5 years were 2.61 times more
      likely to attend than children less than 5 years. When examining parent
      behavioral concerns and child age jointly, only concerns remained significant.
      CONCLUSIONS: Infants and toddlers, who have the highest rates of unmet mental
      health needs, may be least likely to benefit from universal screening and on-site
      MHC support. Efforts to incorporate behaviorally based screening tools and
      increase parent concerns where appropriate appear warranted, particularly for
      families with very young children.

PMID- 24906037
TI  - Ethics in scientific publishing: a 21st century primer.

PMID- 24906039
TI  - A call to arms for an out-of-hospital advanced versus basic airway trial.

PMID- 24906041
TI  - Determination of (210)Po in drinking water and urine samples using copper sulfide
      microprecipitation.
AB  - Polonium-210 ((210)Po) can be rapidly determined in drinking water and urine
      samples by alpha spectrometry using copper sulfide (CuS) microprecipitation. For
      drinking water, Po in 10 mL samples was directly coprecipitated onto the filter
      for alpha counting without any purification. For urine, 10 mL of sample was
      heated, oxidized with KBrO3 for a short time (~5 min), and subsequently
      centrifuged to remove the suspended organic matter. The CuS microprecipitation
      was then applied to the supernatant. Large batches of samples can be prepared
      using this technique with high recoveries (~85%). The figures of merit of the
      methods were determined, and the developed methods fulfill the requirements for
      emergency and routine radioassays. The efficiency and reliability of the
      procedures were confirmed using spiked samples. 

PMID- 24906040
TI  - Administration of secretin (RG1068) increases the sensitivity of detection of
      duct abnormalities by magnetic resonance cholangiopancreatography in patients
      with pancreatitis.
AB  - BACKGROUND & AIMS: Administration of secretin improves noninvasive imaging of the
      pancreatic duct with magnetic resonance cholangiopancreatography (MRCP). We
      performed a large prospective study to investigate whether synthetic human
      secretin (RG1068)-stimulated MRCP detects pancreatic duct abnormalities with
      higher levels of sensitivity than MRCP. METHODS: We performed a phase 3,
      multicenter, baseline-controlled study of patients with acute or acute recurrent
      pancreatitis who were scheduled to undergo endoscopic retrograde
      cholangiopancreatography (ERCP) between March 26, 2008, and October 28, 2009.
      Patients underwent a baseline MRCP that was immediately followed by
      administration of RG1068 and repeat MRCP and then underwent ERCP within 30 days;
      they were followed up for 30 days. MRCP and ERCP images were read centrally by 3
      radiologists and 2 endoscopists, respectively, who were all independent and
      blinded; pancreatic duct abnormalities were evaluated. The accuracy of MRCP was
      evaluated using ERCP as the standard. RESULTS: In total, 258 patients were
      enrolled in the study; 251 MRCP image sets were assessed, and 236 patients had
      evaluable ERCPs. Pancreatic duct abnormalities were observed in 60.2% of ERCP
      images. All radiologists identified duct abnormalities in RG1068-cine MRCP image
      sets with significantly higher levels of sensitivity (P < .0001) than in images
      from MRCP, with minimal loss of specificity. Adverse events were reported in
      38.0% of patients after MRCP and 68.1% after ERCP. Of the 55 patients who
      experienced a serious adverse event, 3 (1.2%) and 52 (20.5%) of the events were
      reported to be temporally associated with MRCP and ERCP, respectively. The
      adverse events most frequently considered related to RG1068 were nausea,
      abdominal pain, and flushing; most were mild. CONCLUSIONS: Compared with images
      from MRCP, those from RG1068-stimulated MRCP are improved in many aspects and
      could aid in diagnosis and clinical decision making for patients with acute,
      acute recurrent, or chronic pancreatitis. RG1068-enhanced MRCP might also better
      identify patients in need of therapeutic ERCP (ClinicalTrials.gov, Number:
      NCT00660335).

PMID- 24906042
TI  - Ultrasonic assisted preparation of lanthanide-oleate complexes for the synthesis
      of multifunctional monodisperse upconversion nanoparticles for multimodal
      imaging.
AB  - The synthesis of multifunctional monodisperse upconversion nanoparticles (UCNPs)
      of high quality is highly desired for bioimaging. Lanthanide-oleate complexes are
      excellent precursors for the synthesis of high quality UCNPs with controllable
      size and shape. In this work, lanthanide-oleate complexes were prepared by an
      ultrasonic assisted procedure, and used as precursors for further synthesis of
      multifunctional monodisperse NaYF4:59%Yb(3+),0.5% Tm(3+)@NaYF4:20%Gd(3+)
      nanoparticles without the need for further purification. Heavy doping of Yb(3+)
      in the core and incorporation of Gd(3+) in the shell made the UCNPs promising for
      upconversion luminescence (UCL), magnetic resonance (MR) and computed tomography
      (CT) multimodal imaging. The nanoparticles were further functionalized with
      bombesin peptide for in vivo UCL/MR/CT imaging of prostate tumors.

PMID- 24906043
TI  - Syringe-type and needle gauge have no role in adverse events following DTwP
      immunization: a randomized multicenter trial.
AB  - BACKGROUND: Auto-Disable syringes are recommended for immunization because of
      their greater safety and preventing reuse. In this study, the role of the syringe
      and needle gauge on the adverse events following Diphtheria, Tetanus toxoids and
      whole-cell Pertussis immunization was studied. METHODS: In this study, 1000
      children from 2 months to 6 years of age, eligible for Diphtheria, Tetanus
      toxoids and whole-cell Pertussis immunization and who referred to 4 health
      centers, were randomized into 2 groups of regular syringe users (the Auto-Disable
      syringe with a 23 gauge and 25 mm needle) and new syringe users (the disposable
      syringe with a 24 gauge and 25 mm needle). Adverse events following immunization
      were evaluated on days 2, 4 and 6 after immunization by visiting the children at
      their home and examining them. RESULTS: The occurrence of the primary endpoint
      (severe local reaction) was found to be 2.1% in all the children, 2.0% in the
      children vaccinated with the Auto-Disable syringe and 2.2% in the children
      vaccinated with the new syringe. This difference is not significant (P = 0.818).
      The evaluation of other milder adverse events (secondary endpoints) showed that
      the syringe type has no effect on the occurrence of these adverse events.
      CONCLUSIONS: Syringe types and needle diameter played no role in precipitating
      the adverse events following immunization of the Diphtheria, Tetanus toxoids and
      whole-cell Pertussis vaccine.

PMID- 24906044
TI  - Targeting IL-34 in chronic inflammation.
AB  - A second ligand for colony-stimulating factor-1 receptor (CSF-1R) with distinct
      biologic activities had long been implicated but not appreciated until the recent
      discovery of interleukin (IL)-34. IL-34 and CSF-1 signal through this common
      receptor to mediate the biology of mononuclear phagocytic cells. Aberrant
      macrophage activation by CSF-1 and/or IL-34 is associated with numerous diseases,
      and clinical therapies targeting this pathway are being tested. Although IL-34
      and CSF-1 have distinct activities under physiologic conditions, they appear
      functionally redundant in various disease states. Thus, blocking the activity of
      both might be necessary for maximal efficacy. 

PMID- 24906046
TI  - Reply: To PMID 23983134.

PMID- 24906047
TI  - High-normal blood pressure, functional capacity and left heart mechanics: is
      there any connection?
AB  - OBJECTIVE: To evaluate the relationship between functional capacity and left
      ventricular (LV) and left atrial (LA) myocardial deformation, assessed by two-
      and three-dimensional (2DE and 3DE) strain analysis, in subjects with high-normal
      blood pressure (BP). METHODS: This cross-sectional study included 64 subjects
      with optimal BP and 75 subjects with high-normal BP of similar gender and age.
      All the subjects underwent a complete 2DE and 3DE examination and cardiopulmonary
      exercise testing. RESULTS: 3DE global longitudinal strain was significantly lower
      in the group with high-normal BP than in the optimal BP group (- 20.1 +/- 2.4 vs 
      18.5 +/- 2.3%, p < 0.001). Similar results were obtained for 3DE global
      circumferential strain (- 21.8 +/- 2.6 vs - 19.3 +/- 2.4%, p < 0.001), as well as
      for 3DE global radial strain (45.1 +/- 8.8 vs 42.3 +/- 7.2%, p = 0.042), and 3DE
      global area strain (- 30.1 +/- 4.2 vs - 28.1 +/- 3.8%, p < 0.001). LV twist was
      similar between the observed groups, whereas untwisting rate was significantly
      decreased in the subjects with high-normal BP (- 123 +/- 30 vs - 112 +/- 26
      degrees /s, p = 0.023). Peak VO2 was significantly lower in the high-normal BP
      group (30.8 +/- 4 vs 28.3 +/- 3.7 ml/kg/min, p < 0.001). 2DE LV ejection fraction
      (beta = 0.38, p = 0.014), 2DE global longitudinal strain (beta = 0.35, p = 0.019)
      and 3DE global longitudinal strain (beta = 0.27, p = 0.042) were independently
      associated with peak VO2. CONCLUSION: LV and LA mechanics, as well as functional
      capacity are significantly impaired in the subjects with high-normal BP. LV and
      LA myocardial deformations are associated with peak oxygen uptake.

PMID- 24906048
TI  - Pesticide exposure and depression among male private pesticide applicators in the
      agricultural health study.
AB  - BACKGROUND: Pesticide exposure may be positively associated with depression. Few
      previous studies have considered the episodic nature of depression or examined
      individual pesticides. OBJECTIVE: We evaluated associations between pesticide
      exposure and depression among male private pesticide applicators in the
      Agricultural Health Study. METHODS: We analyzed data for 10 pesticide classes and
      50 specific pesticides used by 21,208 applicators enrolled in 1993-1997 who
      completed a follow-up telephone interview in 2005-2010. We divided applicators
      who reported a physician diagnosis of depression (n = 1,702; 8%) into those who
      reported a previous diagnosis of depression at enrollment but not follow-up (n =
      474; 28%), at both enrollment and follow-up (n = 540; 32%), and at follow-up but
      not enrollment (n = 688; 40%) and used polytomous logistic regression to estimate
      odds ratios (ORs) and 95% CIs. We used inverse probability weighting to adjust
      for potential confounders and to account for the exclusion of 3,315 applicators
      with missing covariate data and 24,619 who did not complete the follow-up
      interview. RESULTS: After weighting for potential confounders, missing covariate
      data, and dropout, ever-use of two pesticide classes, fumigants and
      organochlorine insecticides, and seven individual pesticides-the fumigants
      aluminum phosphide and ethylene dibromide; the phenoxy herbicide (2,4,5
      trichlorophenoxy)acetic acid (2,4,5-T); the organochlorine insecticide dieldrin;
      and the organophosphate insecticides diazinon, malathion, and parathion-were all
      positively associated with depression in each case group, with ORs between 1.1
      and 1.9. CONCLUSIONS: Our study supports a positive association between pesticide
      exposure and depression, including associations with several specific pesticides.

PMID- 24906049
TI  - Is there an antiandrogen withdrawal syndrome with enzalutamide?
AB  - OBJECTIVE: To examine prostate-specific antigen (PSA) levels after enzalutamide
      discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS)
      exists with enzalutamide. METHODS: We retrospectively identified 30 consecutive
      patients with metastatic prostate cancer who were treated with enzalutamide after
      docetaxel. Post-discontinuation PSA results were available for all patients and
      were determined at 2-weekly intervals until starting further anticancer systemic
      therapy. PSA withdrawal response was defined as a PSA decline by >=50% from the
      last on-treatment PSA, with a confirmed decrease >=3 weeks later. Patient
      characteristics were evaluated in relation to the AAWS using univariate logistic
      regression analysis. RESULTS: The median (range) patient age was 70.5 (56-86)
      years and the median (range) follow-up was 9.0 (0.5-16) months. The most common
      metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients
      (70%) had previously received abiraterone and 12 patients (40%) had also received
      cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68
      (1.12-21.39) months. PSA levels after enzalutamide withdrawal were monitored for
      a median (range) time of 35 (10-120) days. Only one patient (3.3%) had a
      confirmed PSA response >=50% after enzalutamide discontinuation. One patient
      (3.3%) had a confirmed PSA response of between 30 and 50% and another patient
      (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall
      survival was 15.5 months (95% CI 8.1-24.7). None of the factors analysed in the
      univariate analysis were significant predictors of PSA decline after enzalutamide
      discontinuation. CONCLUSIONS: This retrospective study provides the first
      evidence that enzalutamide may have an AAWS in a minority of patients with
      metastatic castration-resistant prostate cancer. Further studies are needed to
      confirm the existence of an enzalutamide AAWS and to assess its relevance in
      prostate cancer management.

PMID- 24906050
TI  - Engineered minichromosomes in plants.
AB  - Platforms for the development of synthetic chromosomes in plants have been
      produced in several species using telomere mediated chromosomal truncation with
      the simultaneous inclusion of sites that facilitate further additions to the
      newly generated minichromosome. By utilizing truncated supernumerary or B
      chromosomes, the output of the genes on the minichromosome can be amplified.
      Proof of concept experiments have been successful illustrating that
      minichromosome platforms can be modified in vivo. Engineered minichromosomes can
      likely be combined with haploid breeding if they are incorporated into inducer
      lines given that the observations that basically inert chromosomes from haploid
      inducer lines can be recovered at workable frequencies in otherwise haploid
      plants. Future needs of synthetic chromosome development are discussed. 

PMID- 24906052
TI  - First mtDNA sequencing of Volga and Ob basin taimen Hucho taimen: European
      populations stem from a late Pleistocene expansion of H. taimen out of western
      Siberia and are not intermediate to Hucho hucho.
AB  - New concatenated mtDNA sequences (three genes; n = 22) of Siberian taimen Hucho
      taimen primarily from west Siberian and European regions of the species' range
      were added to 12 previously published sequences to provide a phylogeographic
      overview of the species. European samples show only very minor divergence from
      west Siberian populations, supporting a late Pleistocene expansion from Siberia
      into the Urals, with no particular relation to the Danube River basin huchen
      Hucho hucho as once hypothesized. The disjunct distribution of the genus is most
      likely based on an early Pleistocene vicariant event. 

PMID- 24906051
TI  - One-pot isomerization-cross metathesis-reduction (ICMR) synthesis of lipophilic
      tetrapeptides.
AB  - An efficient, versatile and rapid method toward homologue series of lipophilic
      tetrapeptide derivatives (herein, the opioid peptides H-TIPP-OH and H-DIPP-OH) is
      reported. High atom economy and a minimal number of synthetic steps resulted from
      a one-pot tandem isomerization-cross metathesis-reduction sequence (ICMR),
      applicable both in solution and solid phase methodology. The broadly applicable
      synthesis proceeds with short reaction times and simple work-up, as illustrated
      in this work for alkylated opioid tetrapeptides. 

PMID- 24906053
TI  - Sex differences in learning and memory following short-term dietary restriction
      in the rat.
AB  - INTRODUCTION: Acute or prolonged dietary restriction has been shown to have
      significant effects on learning and memory, and also on the food seeking
      behaviour in animals. AIM: This study investigated whether or not there are sex
      differences in spatial learning and memory following short-term dietary
      restriction in the rat. METHODS: Two month-old male (n=24) and female (n=24)
      Sprague-Dawley rats were randomly assigned to either (1) male or female control
      (i.e. normal diet regimen); (2) male or female 40% dietary restriction for either
      2 hours (2h-DR) or 2 weeks (2 wks-DR) duration. Following the restriction
      paradigm (i.e. either 2h or 2 weeks), animals were weighed, and learning and
      memory was assessed daily for a total of 5 days by Morris Water Maze. RESULTS:
      Dietary restriction for 2h provoked high speed swimming in female rats compared
      to controls. However the females performance in water maze was inferior to the
      control animals. Two weeks after 40% DR resulted in reduction of male's body
      weight by 20% compared to their control group. However, both males and females
      showed difficulties in water maze learning and memory test after the 2 weeks 40%
      DR. The animals swam longer distance and took longer time to reach the platform
      when compared to their age-matched controls. CONCLUSION: In fully developed
      brain, adult animal's cognitive performance is shown to be affected by acute and
      prolonged stress in the form of food restriction. Interestingly, the impact of
      this stress was different according to the sex of the animals. In female rats,
      dietary restriction has a negative effect on learning and memory after 2h and 2
      weeks intervals. In male rats, 2h of DR has a positive effect on learning and
      memory; however this effect is not maintained and by 2 weeks there is a negative
      effect similar to that seen in female animals.

PMID- 24906054
TI  - Hybrid voltage sensor imaging of eGFP-F expressing neurons in chicken midbrain
      slices.
AB  - BACKGROUND: Dendritic computation is essential for understanding information
      processing in single neurons and brain circuits. Optical methods are suited best
      to investigate function and biophysical properties of cellular compartments at
      high spatial and temporal resolution. Promising approaches include the use of
      voltage sensitive dyes, genetically encoded voltage sensors, or hybrid voltage
      sensors (hVoS) consisting of fluorescent proteins and voltage-dependent quenchers
      that, so far, are not available in avian neuroscience. NEW METHOD: We have
      adapted a hVoS system for a chicken midbrain slice preparation by combining
      genetically expressed farnesylated eGFP with dipicrylamine (DPA). Depending on
      the cellular potential, DPA is shifted in the membrane, resulting in quenching of
      eGFP fluorescence linearly to the membrane potential by Forster resonance
      electron transfer. RESULTS: In ovo electroporation resulted in labelled neurons
      throughout the midbrain with a high level of fine structural detail. After
      application of DPA, we were able to optically record electrically evoked action
      potentials with high signal-to-noise ratio and high spatio-temporal resolution.
      COMPARISON WITH EXISTING METHODS: Standard methods available for avian
      neuroscience such as whole-cell patch clamp yield insufficient data for the
      analysis of dendritic computation in single neurons. The high spatial and
      temporal resolution of hVoS data overcomes this limitation. The results obtained
      by our method are comparable to hVoS data published for mammals. CONCLUSIONS:
      With the protocol presented here, it is possible to optically record information
      processing in single avian neurons at such high spatial and temporal resolution,
      that cellular and subcellular events can be analysed.

PMID- 24906055
TI  - A novel traumatic brain injury model for induction of mild brain injury in rats.
AB  - BACKGROUND: Due to the marked heterogeneity of human traumatic brain injury
      (TBI), none of the available animal model can reproduce the entire spectrum of
      TBI, especially mild focal TBI. This study was designed to develop a modified TBI
      weight drop model for induction of focal mild cerebral injury. NEW METHOD: A
      stereotaxic coupled weight drop device was designed. Principle arm of device
      carries up to 500g weights which their force was conveyed to animal skull through
      a thin nail like metal tip. To determine the optimal configuration of the device
      to induce mild TBI, six different trials were designed. The optimal configuration
      of the instrument was used for evaluation of behavioral, histopathological and
      molecular changes of mild TBI. RESULTS: Neurologic and motor coordination
      deficits observed sharply within 24h post injury period. Histological studies
      revealed a remarkable increase in the number of dark neurons in trauma site. TBI
      increased the expression of apoptotic proteins, Bax, BCl2 and cleaved caspase-3
      in the hippocampus. COMPARISON WITH EXISTING METHODS: Our designed TBI device is
      capable to produce variable severity of TBI from mild to severe. The main
      advantage of the new TBI model is induction of mild local unilateral brain injury
      instead of traumatization of the whole brain. This model does not require
      craniotomy for induction of brain injury. CONCLUSION: This novel animal TBI model
      mimics human mild focal brain injury. This model is suitable for evaluation of
      pathophysiology as well as screening of new therapies for mild TBI.

PMID- 24906056
TI  - Isoforms of wild type proteins often appear as low molecular weight bands on SDS
      PAGE.
AB  - Immunoblotting, after polyacrylamide gel electrophoresis with sodium dodecyl
      sulfate (SDS-PAGE), is a technique commonly used to detect specific proteins. SDS
      PAGE often results in the visualization of protein band(s) in addition to the one
      expected based on the theoretical molecular mass (TMM) of the protein of
      interest. To determine the likelihood of additional band(s) being nonspecific, we
      used liquid chromatography - mass spectrometry to identify proteins that were
      extracted from bands with the apparent molecular mass (MM) of 40 and 26 kD,
      originating from protein extracts derived from non-malignant HEK293 and cancerous
      MDA-MB231 (MB231) cells separated using SDS-PAGE. In total, approximately 57% and
      21% of the MS/MS spectra were annotated as peptides in the two cell samples,
      respectively. Moreover, approximately 24% and 36.2% of the identified proteins
      from HEK293 and MB231 cells matched their TMMs. Of the identified proteins, 8%
      from HEK293 and 26% from MB231 had apparent MMs that were larger than predicted,
      and 67% from HEK293 and 37% from MB231 exhibited smaller MM values than
      predicted. These revelations suggest that interpretation of the positive bands of
      immunoblots should be conducted with caution. This study also shows that protein
      identification performed by mass spectrometry on bands excised from SDS-PAGE gels
      could make valuable contributions to the identification of cancer biomarkers, and
      to cancer-therapy studies. 

PMID- 24906057
TI  - Geometric matching principle for adsorption selectivity of ionic liquids: a
      simple method into the fascinating world of shape-controlled chemistry.
AB  - Ionic liquids (ILs) possess effective functions in controlling the phase and
      morphology of nanomaterials. However, it is still unclear how ILs affect the
      morphology control and what the origin of adsorption selectivity of ILs is on
      different crystal facets. It is a challenge to develop a simple method to select
      the suitable kinds of ILs for achieving the controllable synthesis of
      nanomaterials with designable shape. Herein, density functional theory (DFT)
      calculations were combined with experiment to study the interaction mechanism
      between ILs and crystal facets. An important relationship is proposed, named as
      the geometric matching principle, in which the adsorption site of substrate
      should not only need to meet the space requirement for interionic stacking of
      ILs, but also needs to maximize the interaction between adsorbed ILs and
      substrate. This new finding is meaningful for prediction of the adsorption
      selectivity of ILs and clarification of their shape-controlled chemistry. 

PMID- 24906058
TI  - Factors associated with concordance between parental-reported use and dispensed
      asthma drugs in adolescents: findings from the BAMSE birth cohort.
AB  - PURPOSE: Pharmacological treatment is important in asthma care, but there are
      methodological challenges in measuring how drugs are used by patients. The aim of
      this study was to investigate the concordance between register data on dispensed
      drugs and parental-reported use of asthma drugs in adolescents. METHODS: A cross
      sectional study comparing data on dispensed drugs from the Swedish Prescribed
      Drug Register with data on parental-reported use of asthma drugs among 3 316
      adolescents (age 11-14 years) in a population-based birth cohort in Sweden.
      Sensitivity, specificity, and positive predicted value for different time windows
      (3, 6, 12, 18, and 24 months) for dispensing in the register were computed.
      Logistic regression was used to explore factors associated with concordance.
      RESULTS: The prevalence of parental-reported use of asthma drugs in the past year
      was 10.7% (n = 356) compared with 8.1% (n = 269) for dispensed drugs according to
      the register (p <= 0.001). The sensitivity increased with an extended time window
      in the register, whereas the specificity remained high up to 18 months. Although
      90% of the adolescents with asthma had parental-reported use of asthma drugs, 30%
      of them had no such drugs dispensed in the preceding 18 months. The highest
      concordance was seen for adolescents with severe asthma (OR 4.6, CI 1.2-17.6).
      CONCLUSIONS: An 18-month window is preferable when using dispensing data to study
      the use of asthma drugs. Still, many adolescents with reported drug use had not
      purchased any asthma drug in this period. The concordance between parental
      reported use and dispensed drugs is higher for adolescents with severe asthma.

PMID- 24906059
TI  - Assessing radiation emergency preparedness planning by using community assessment
      for public health emergency response (CASPER) methodology.
AB  - INTRODUCTION: Approximately 1.2 million persons in Oakland County, Michigan (USA)
      reside less than 50 miles from the Fermi Nuclear Power Plant, Unit 2, but
      information is limited regarding how residents might react during a radiation
      emergency. Community Assessment for Public Health Emergency Response (CASPER)
      survey methodology has been used in disaster and non disaster settings to collect
      reliable and accurate population-based public health information, but it has not
      been used to assess household-level emergency preparedness for a radiation
      emergency. To improve emergency preparedness plans in Oakland County, including
      how residents might respond during a radiation emergency, Oakland County Health
      Division (OCHD), with assistance from the Centers for Disease Control and
      Prevention (CDC) and the Michigan Department of Community Health (MDCH),
      conducted a CASPER survey. METHODS: During September 2012, a 2-stage cluster
      sampling design was used to select 210 representative households in Oakland
      County. By using in-person surveys, the proportion of households with essential
      needs and supplies, how residents might respond to public health authorities'
      instructions, and their main source for obtaining information during a radiation
      emergency were assessed. Data were weighted to account for the complex sampling
      design. RESULTS: Of the goal of 210 households, 192 (91.4%) surveys were
      completed: 64.7% and 85.4% of respondents indicated having 3-day supplies of
      water and of non perishable food, respectively; 62.8% had a 7-day supply of
      prescription medication for each person who needed it. Additionally, 64.2% had a
      working carbon monoxide detector; 67.1% had a first-aid kit; and 52% had an
      alternative heat source. In response to instructions from public health officials
      during a radiation emergency, 93.3% of all respondents would report to a
      radiation screening center; 96% would evacuate; and 91.8% would shelter-in-place.
      During a radiation emergency, 55.8% of respondents indicated their main
      information source would be television, 18.4% radio, and 13.6% the Internet. The
      most trusted source for information would be the local public health department
      (36.5%), local news (23%), a physician (11.2%), and family members (11.1%).
      Including completed and incomplete interviews, refusals, and non respondents, 517
      total households were contacted. CONCLUSIONS: CASPER data regarding how residents
      might react during a radiation emergency provided objective and quantifiable
      information that will be used to develop Oakland County's radiation emergency
      preparedness plans. Survey information demonstrates the feasibility and
      usefulness of CASPER methodology for radiation emergency preparedness planning.

PMID- 24906060
TI  - An Evaluation of Statistical Methods for Analyzing Follow-Up Gaussian Laboratory
      Data with a Lower Quantification Limit.
AB  - Laboratory data with a lower quantification limit (censored data) are sometimes
      analyzed by replacing non-quantifiable values with a single value equal to or
      less than the quantification limit, yielding possibly biased point estimates and
      variance estimates that are too small. Motivated by a three-period, three
      treatment crossover study of a candidate vaginal microbicide in human
      immunodeficiency virus (HIV)-infected women, we consider four analysis methods
      for censored Gaussian data with a single follow-up measurement: nonparametric
      methods, mixed models, mixture models, and dichotomous measures of a treatment
      effect. We apply these methods to the crossover study data and use simulation to
      evaluate the statistical properties of these methods in analyzing the treatment
      effect in a two-treatment parallel-arm or crossover study with censored Gaussian
      data. Our simulated data and our mixed and mixture models consider treated follow
      up data with the same variance as the baseline data or with an inflated variance.
      Mixed models have the correct type I error, the best power, the least biased
      Gaussian parameter treatment-effect estimates, and appropriate confidence
      interval coverage for these estimates. A crossover study analysis with a period
      effect can greatly increase the required study sample size. For both designs and
      both variance assumptions, published sample-size estimation methods do not yield
      a good estimate of the sample size to obtain the stated power. 

PMID- 24906061
TI  - Validity of self-reported exposure to second-hand smoke in hospitality venues.
AB  - The aim was to assess the validity of self-reported exposure to second-hand smoke
      (SHS) in 50 hospitality venues of Madrid (Spain) in 2010, taking as a reference
      vapour-phase nicotine measured by active sampling. The questions posed in the
      questionnaire permitted distinguishing between the different levels of SHS.
      However, the moderate relationship found (Spearman's correlation=0.387, p<0.001)
      suggests that intensity of exposure to SHS in hospitality venues, based solely on
      self-reported information, should be used with caution. 

PMID- 24906064
TI  - Occurrence of triazole-resistant Aspergillus fumigatus with TR34/L98H mutations
      in outdoor and hospital environment in Kuwait.
AB  - BACKGROUND: Invasive aspergillosis due to triazole-resistant Aspergillus
      fumigatus, a common airborne fungal pathogen, has emerged in some European and
      Asian countries, likely due to exposure to azole fungicides in the environment.
      This study determined the occurrence of triazole-resistant A. fumigatus in
      outdoor and hospital environment in Kuwait, a semi-arid desert country in Arabian
      Peninsula. METHODS: Outdoor/indoor air, water and cotton swab samples were
      cultured on malt extract agar and A. fumigatus colonies were identified by
      phenotypic and molecular methods. Drug susceptibility of A. fumigatus isolates to
      itraconazole, posaconazole and voriconazole was carried out by an Etest and a
      broth microdilution method. Resistance mechanisms involving cyp51A mutations were
      probed by mixed-format real-time (MF-rt)-PCR assays. Triazole-resistant isolates
      were typed by nine-locus microsatellite analysis. A multiplex allele-specific
      (MAS)-PCR assay was developed for detection of L98H mutation in cyp51A. RESULTS:
      Of 115 A. fumigatus isolates obtained from 362 environmental samples from across
      Kuwait, 8 isolates were resistant to itraconazole, posaconazole and voriconazole.
      All itraconazole-resistant isolates contained a 34-bp tandem repeat (TR34) in the
      promoter region and a L98H mutation at codon 98 (TR34/L98H) in cyp51A. These
      mutations were absent in all itraconazole-susceptible isolates. MAS-PCR
      accurately detected L98H mutation in all triazole-resistant isolates. Three
      microsatellite patterns were observed among resistant isolates with one pattern
      clustering with Indian clinical and environmental isolates. CONCLUSIONS: Triazole
      resistant A. fumigatus with TR34/L98H mutations in cyp51A is prevalent in Kuwait.
      Although triazole-resistant A. fumigatus has not yet been isolated from clinical
      specimens, its presence in the environment suggests that the possibility of
      susceptible individuals getting infected with such strains exists and may pose
      therapeutic challenges in its management.

PMID- 24906062
TI  - Peak expiratory flow, breath rate and blood pressure in adults with changes in
      particulate matter air pollution during the Beijing Olympics: a panel study.
AB  - OBJECTIVES: This study aims to examine whether changes in short-term exposures to
      particulate matter are associated with changes in lung function, breath rate, and
      blood pressure among healthy adults and whether smoking status modifies the
      association. METHODS: We took advantage of the artificially controlled changes in
      air pollution levels that occurred during the 2008 Olympic Games in Beijing,
      China and conducted a panel study of 201 Beijing residents. Data were collected
      before, during, and after the Olympics, respectively. Linear mixed-effect models
      and generalized estimating equation models were used to compare measurements of
      peak expiratory flow, breath rate and blood pressure across three time points.
      RESULTS: The mean values of peak expiratory flow were 346.0 L/min, 399.3 L/min,
      and 364.1L/min over the three study periods. Peak expiratory flow levels
      increased in 78% of the participants when comparing the during- with pre-
      Olympics time points, while peak expiratory flow levels decreased in 80% of
      participants for the post- and during-Olympic periods comparison. In subgroup
      analyses comparing the during-Olympic to pre-Olympic time points, we found a
      larger percentage change in peak expiratory flow (+17%) among female, younger and
      non-smoking participants than among male, elderly and smoking participants
      (+12%). The percentage of participants with a fast breath rate (>20/min) changed
      from 9.7% to 4.9% to 30.1% among females, and from 7.9% to 2.6% to 27.3% among
      males over the three time points. The changes in blood pressure over the three
      study periods were not very clear, although there is an increase in diastolic
      pressure and a decrease in pulse pressure among males during the games.
      CONCLUSIONS: The results suggest that exposure to different air pollution levels
      has significant effects on respiratory function. Smoking, age and gender appear
      to modify participants' biological response to changes in air quality.

PMID- 24906065
TI  - Formaldehyde: a chemical of concern in the vicinity of MBT plants of municipal
      solid waste.
AB  - The mechanical-biological treatment (MBT) of municipal solid waste (MSW) has a
      number of advantages in comparison to other MSW management possibilities.
      However, adverse health effects related to this practice are not well known yet,
      as a varied typology of microbiological and chemical agents may be generated and
      released. In 2010, we initiated an environmental monitoring program to control
      air levels of volatile organic compounds (VOCs) and microbiological pollutants
      near an MBT plant in Montcada i Reixac (Catalonia, Spain). In order to assess any
      temporal and seasonal trends, four 6-monthly campaigns were performed. Important
      fluctuations were observed in the levels of different biological indicators
      (total and Gram-negative bacteria, fungi grown at 25  degrees C and 37  degrees
      C, and more specifically, Aspergillus fumigatus). Although overall bioaerosols
      concentrations were rather low, a certain increase in the mean values of bacteria
      and fungi was observed in summer. In contrast, higher concentrations of VOCs were
      found in winter, with the only exception of formaldehyde. Interestingly, although
      this compound was not detected in one of the sampling campaigns, current airborne
      levels of formaldehyde were higher than those previously reported in urban areas
      across Europe. Furthermore, the non-carcinogenic risks (Hazard Quotient),
      particularly in winter, as well as the cancer risks associated with the
      inhalation of VOCs, exceeded the threshold values (1 and 10(-5), respectively),
      reaffirming the need of continuing with the monitoring program, with special
      emphasis on formaldehyde, a carcinogenic/mutagenic substance.

PMID- 24906063
TI  - Dietary predictors of urinary environmental biomarkers in young girls, BCERP,
      2004-7.
AB  - BACKGROUND: Exposures of children to phthalates, parabens, and bisphenol-A (BPA)
      are of concern because of their hormonal potential. These agents are found in a
      wide range of foods and packaging. We investigated whether intake of certain
      foods predict exposures to these chemicals in young girls. METHODS: Among 1101
      girls (6-8 years at enrollment) from the Breast Cancer and Environment Research
      Program (BCERP) study, we measured urinary exposure biomarkers for phthalates,
      parabens, and BPA and assessed dietary intake using 24-h recall 2-4 times. We
      examined the average daily servings of major and minor food groups categorized as
      0 to <0.5, 0.5 to <1 and >= 1 servings per day. Items included dairy, eggs, fats,
      fish, fruit, single grains, meat, non-poultry meats, pasta, poultry and
      vegetables. Covariate-adjusted least squares geometric means and 95% confidence
      intervals of creatinine-corrected phthalate and phenol metabolite concentrations
      in urine were calculated in relation to food intake. RESULTS: Grains, flour and
      dry mixes and total fish consumption were positively associated with BPA and the
      sum of four di-2-ethylhexylphthalate (DEHP) urinary metabolite concentrations.
      Non-fresh vegetables and poultry were both positively associated with BPA and
      paraben urinary concentrations. Fats, oils and poultry consumption were
      positively associated with BPA. Whole-fat dairy consumption was associated with
      SigmaDEHP. CONCLUSIONS: Some foods may contribute to child exposures to certain
      chemicals, and this may constitute modifiable means to reduce these environmental
      exposures.

PMID- 24906066
TI  - Total and cardiovascular mortality rates in relation to discharges from Toxics
      Release Inventory sites in the United States.
AB  - BACKGROUND: This study analyzed Toxics Release Inventory (TRI) discharges in
      association with covariate-adjusted total and cardiovascular mortality rates for
      males and females in US counties. METHODS: Average annual county-level reported
      releases from TRI facilities measured in pounds per square mile which were
      calculated for the years 1990-1999, and tested for associations with age-adjusted
      mortality rates for 2006-2010. Chemicals were grouped into four categories: 1)
      carcinogens, 2) metals, 3) hazardous air pollutants, and 4) chemicals in the
      Comprehensive Environmental Response, Compensation and Liability Act. For each of
      these chemical groups the reported total, water, and air emissions were measured.
      Age-adjusted mortality rates were found separately for males and females from the
      Centers for Disease Control and Prevention for total and cardiovascular disease.
      Covariates included rates of smoking, obesity, high school and college education,
      race/ethnicity, poverty, unemployment, percent without health insurance, and
      urban-rural setting. Data were analyzed using multiple linear regression models.
      RESULTS: Greater average annual TRI releases in 1990-1999 in all four chemical
      categories were significantly associated with higher mortality rates in 2006-2010
      for both total and cardiovascular mortality, and for both males and females,
      adjusted for covariates. Associations were stronger for air releases than for
      water releases. CONCLUSIONS: This study provides the first evidence that greater
      amounts of TRI releases are related to higher population mortality rates for
      cardiovascular disease. In addition, the study showed that adverse TRI effects
      were broadly present for both males and females for multiple chemical groups.
      Further progress is needed to reduce the use and release of harmful chemicals
      from TRI facilities in the United States.

PMID- 24906068
TI  - Combined effects of road traffic noise and ambient air pollution in relation to
      risk for stroke?
AB  - Exposure to road traffic noise and air pollution have both been associated with
      risk for stroke. The few studies including both exposures show inconsistent
      results. We aimed to investigate potential mutual confounding and combined
      effects between road traffic noise and air pollution in association with risk for
      stroke. In a population-based cohort of 57,053 people aged 50-64 years at
      enrollment, we identified 1999 incident stroke cases in national registries,
      followed by validation through medical records. Mean follow-up time was 11.2
      years. Present and historical residential addresses from 1987 to 2009 were
      identified in national registers and road traffic noise and air pollution were
      modeled for all addresses. Analyses were done using Cox regression. A higher mean
      annual exposure at time of diagnosis of 10 ug/m(3) nitrogen dioxide (NO2) and 10
      dB road traffic noise at the residential address was associated with ischemic
      stroke with incidence rate ratios (IRR) of 1.11 (95% CI: 1.03, 1.20) and 1.16
      (95% CI: 1.07, 1.24), respectively, in single exposure models. In two-exposure
      models road traffic noise (IRR: 1.15) and not NO2 (IRR: 1.02) was associated with
      ischemic stroke. The strongest association was found for combination of high
      noise and high NO2 (IRR=1.28; 95% CI=1.09-1.52). Fatal stroke was positively
      associated with air pollution and not with traffic noise. In conclusion, in
      mutually adjusted models road traffic noise and not air pollution was associated
      ischemic stroke, while only air pollution affected risk for fatal strokes. There
      were indications of combined effects.

PMID- 24906067
TI  - Green space and mortality following ischemic stroke.
AB  - BACKGROUND: Residential proximity to green space has been associated with
      physical and mental health benefits, but whether green space is associated with
      post-stroke survival has not been studied. METHODS: Patients >= 21 years of age
      admitted to the Beth Israel Deaconess Medical Center (BIDMC) between 1999 and
      2008 with acute ischemic stroke were identified. Demographics, presenting
      symptoms, medical history and imaging results were abstracted from medical
      records at the time of hospitalization for stroke onset. Addresses were linked to
      average Normalized Difference Vegetation Index, distance to roadways with more
      than 10,000 cars/day, and US census block group. Deaths were identified through
      June 2012 using the Social Security Death Index. RESULTS: There were 929 deaths
      among 1645 patients with complete data (median follow up: 5 years). In
      multivariable Cox models adjusted for indicators of medical history, demographic
      and socioeconomic factors, the hazard ratio for patients living in locations in
      the highest quartile of green space compared to the lowest quartile was 0.78 (95%
      Confidence Interval: 0.63-0.97) (p-trend = 0.009). This association remained
      statistically significant after adjustment for residential proximity to a high
      traffic road. CONCLUSIONS: Residential proximity to green space is associated
      with higher survival rates after ischemic stroke in multivariable adjusted
      models. Further work is necessary to elucidate the underlying mechanisms for this
      association, and to better understand the exposure-response relationships and
      susceptibility factors that may contribute to higher mortality in low green space
      areas.

PMID- 24906069
TI  - Agent Orange exposure and disease prevalence in Korean Vietnam veterans: the
      Korean veterans health study.
AB  - Between 1961 and 1971, military herbicides were used by the United States and
      allied forces for military purposes. Agent Orange, the most-used herbicide, was a
      mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5
      trichlorophenoxyacetic acid, and contained an impurity of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Many Korean Vietnam veterans were exposed to
      Agent Orange during the Vietnam War. The aim of this study was to evaluate the
      association between Agent Orange exposure and the prevalence of diseases of the
      endocrine, nervous, circulatory, respiratory, and digestive systems. The Agent
      Orange exposure was assessed by a geographic information system-based model. A
      total of 111,726 Korean Vietnam veterans were analyzed for prevalence using the
      Korea National Health Insurance claims data from January 2000 to September 2005.
      After adjusting for covariates, the high exposure group had modestly elevated
      odds ratios (ORs) for endocrine diseases combined and neurologic diseases
      combined. The adjusted ORs were significantly higher in the high exposure group
      than in the low exposure group for hypothyroidism (OR=1.13), autoimmune
      thyroiditis (OR=1.93), diabetes mellitus (OR=1.04), other endocrine gland
      disorders including pituitary gland disorders (OR=1.43), amyloidosis (OR=3.02),
      systemic atrophies affecting the nervous system including spinal muscular atrophy
      (OR=1.27), Alzheimer disease (OR=1.64), peripheral polyneuropathies (OR=1.09),
      angina pectoris (OR=1.04), stroke (OR=1.09), chronic obstructive pulmonary
      diseases (COPD) including chronic bronchitis (OR=1.05) and bronchiectasis
      (OR=1.16), asthma (OR=1.04), peptic ulcer (OR=1.03), and liver cirrhosis
      (OR=1.08). In conclusion, Agent Orange exposure increased the prevalence of
      endocrine disorders, especially in the thyroid and pituitary gland; various
      neurologic diseases; COPD; and liver cirrhosis. Overall, this study suggests that
      Agent Orange/2,4-D/TCDD exposure several decades earlier may increase morbidity
      from various diseases, some of which have rarely been explored in previous
      epidemiologic studies. 

PMID- 24906070
TI  - Exposure to traffic pollution, acute inflammation and autonomic response in a
      panel of car commuters.
AB  - BACKGROUND: Exposure to traffic pollution has been linked to numerous adverse
      health endpoints. Despite this, limited data examining traffic exposures during
      realistic commutes and acute response exists. OBJECTIVES: We conducted the
      Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and
      health study, to measure chemically-resolved in-vehicle exposures and
      corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary
      and systemic inflammation and autonomic response. METHODS: We recruited 42 adults
      (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes
      during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle
      particulate components were measured in the subjects' private vehicles. Biomarker
      measurements were conducted before, during, and immediately after the commutes
      and in 3 hourly intervals after commutes. RESULTS: At measurement time points
      within 3h after the commute, we observed mild to pronounced elevations relative
      to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled
      malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative
      stress initiation, as well as decreases relative to baseline levels in the time
      domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic
      dysfunction. We did not observe any detectable changes in lung function
      measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter
      or other systemic biomarkers of vascular injury. Water soluble organic carbon was
      associated with changes in eNO at all post-commute time-points (p<0.0001).
      CONCLUSIONS: Our results point to measureable changes in pulmonary and autonomic
      biomarkers following a scripted 2-h highway commute.

PMID- 24906071
TI  - Distribution of chemical elements in soils and stream sediments in the area of
      abandoned Sb-As-Tl Allchar mine, Republic of Macedonia.
AB  - The aim of this study was to investigate the distribution of some toxic elements
      in topsoil and subsoil, focusing on the identification of natural and
      anthropogenic element sources in the small region of rare As-Sb-Tl mineralization
      outcrop and abandoned mine Allchar known for the highest natural concentration of
      Tl in soil worldwide. The samples of soil and sediments after total digestion
      were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) and
      inductively coupled plasma-atomic emission spectrometry (ICP-AES). Factor
      analysis (FA) was used to identify and characterize element associations. Six
      associations of elements were determined by the method of multivariate
      statistics: Rb-Ta-K-Nb-Ga-Sn-Ba-Bi-Li-Be-(La-Eu)-Hf-Zr-Zn-In-Pd-Ag-Pt-Mg; Tl-As
      Sb-Hg; Te-S-Ag-Pt-Al-Sc-(Gd-Lu)-Y; Fe-Cu-V-Ge-Co-In; Pd-Zr-Hf-W-Be and Ni-Mn-Co
      Cr-Mg. The purpose of the assessment was to determine the nature and extent of
      potential contamination as well as to broadly assess possible impacts to human
      health and the environment. The results from the analysis of the collected
      samples in the vicinity of the mine revealed that As and Tl elements have the
      highest median values. Higher median values for Sb are obviously as a result of
      the past mining activities and as a result of area surface phenomena in the past.

PMID- 24906072
TI  - The impact of heatwaves on workers' health and safety in Adelaide, South
      Australia.
AB  - This study aims to investigate the impact of heatwaves on worker's health and
      safety; to identify workers at higher risk of prevalent illnesses and injuries
      due to heatwaves; and to provide evidence for policy-makers and service
      providers. South Australian workers' compensation claims data for 2001-2010 were
      transformed into time series format, merged with meteorological data and analysed
      using generalized estimating equation (GEE) models. For total injury claims there
      was no significant difference detected between heatwave and non-heatwave periods.
      However, for outdoor industries, daily claims increased significantly by 6.2%
      during heatwaves. Over-represented in hot weather were male labourers and
      tradespersons aged >= 55 years, and those employed in 'agriculture, forestry and
      fishing' and 'electricity, gas and water'. Occupational burns, wounds,
      lacerations, and amputations as well as heat illnesses were significantly
      associated with heatwaves. Similarly, moving objects, contact with chemicals, and
      injuries related to environmental factors increased significantly during
      heatwaves, especially among middle-aged and older male workers. With the
      predicted increase of extremely hot weather, there is a need for relevant
      adaptation and prevention measures at both practice and policy levels for
      vulnerable work groups.

PMID- 24906073
TI  - Modeling horizontal and vertical variation in intraurban exposure to PM2.5
      concentrations and compositions.
AB  - Land use regression (LUR) models are increasingly used to evaluate intraurban
      variability in population exposure to fine particulate matter (PM2.5). However,
      most of these models lack information on PM2.5 elemental compositions and
      vertically distributed samples. The purpose of this study was to evaluate
      intraurban exposure to PM2.5 concentrations and compositions for populations in
      an Asian city using LUR models, with special emphasis on examining the effects of
      having measurements on different building stories. PM2.5 samples were collected
      at 20 sampling sites below the third story (low-level sites). Additional
      vertically stratified sampling sites were set up on the fourth to sixth (mid
      level sites, n=5) and seventh to ninth (high-level sites, n=5) stories. LUR
      models were built for PM2.5, copper (Cu), iron (Fe), potassium (K), manganese
      (Mn), nickel (Ni), sulfur (S), silicon (Si), and zinc (Zn). The explained
      concentration variance (R(2)) of the PM2.5 model was 65%. R(2) values were >69%
      in the Cu, Fe, Mn, Ni, Si, and Zn models and <44% in the K and S models. Sampling
      height from ground level was a significant predictor in the PM2.5 and Si models.
      This finding stresses the importance of collecting vertically stratified
      information on PM2.5 mass concentrations to reduce potential exposure
      misclassification in future health studies. In addition to traffic variables,
      some models identified gravel-plant, industrial, and port variables with large
      buffer zones as important predictors, indicating that PM from these sources had
      significant effects at distant places. 

PMID- 24906075
TI  - Acute cellular rejection versus recurrent hepatitis C after liver
      transplantation: Clinical and pathological features driving a rational diagnostic
      approach.
AB  - AIM: The aim of our study was develop and validate an algorithm system based on
      morphological features for finding the differences between recurrent hepatitis C
      virus (HCV) and acute cellular rejection (ACR) in liver biopsies of HCV
      transplanted patients. METHODS: Two hundred and eighty-eight liver biopsies were
      analyzed from 121 patients transplanted for HCV. A diagnostic consensus was
      reached between clinicians and pathologists in 214 biopsies for the diagnosis of
      recurrent HCV or ACR. A random sample of 114 liver biopsies (derivation cohort)
      was taken to generate the diagnostic tree and was subsequently evaluated using
      the validation cohort in 100 liver biopsies by recursive partitioning analysis of
      morphological variables and time since transplantation. RESULTS: The presence of
      endotheliitis together with a time of less than 6 weeks since LT definitely
      excluded recurrent HCV. After obtaining the regression tree, diagnostic accuracy
      was 96% and 93% in the derivation and validation cohort, respectively. Both cases
      surpassed the pathologist's original diagnosis, which had a diagnostic accuracy
      of 91% (P < 0.05, for both comparisons). CONCLUSION: A recursive partitioning
      analysis of the morphological features in liver biopsies from HCV-transplanted
      patients may be useful for easily distinguishing between recurrent HCV and ACR.

PMID- 24906074
TI  - Assessment of primary and secondary ambient particle trends using satellite
      aerosol optical depth and ground speciation data in the New England region,
      United States.
AB  - The effectiveness of air pollution emission control policies can be evaluated by
      examining ambient pollutant concentration trends that are observed at a large
      number of ground monitoring sites over time. In this paper, we used ground
      monitoring measurements in conjunction with satellite aerosol optical depth (AOD)
      data to investigate fine particulate matter (PM2.5; particulate matter with
      aerodynamic diameter <= 2.5 um) trends and their spatial patterns over a large
      U.S. region, New England, during 2000-2008. We examined the trends in rural and
      urban areas to get a better insight about the trends of regional and local source
      emissions. Decreases in PM2.5 concentrations (ug/m(3)) were more pronounced in
      urban areas than in rural ones. In addition, the highest and lowest PM2.5
      decreases (ug/m(3)) were observed for winter and summer, respectively. Together,
      these findings suggest that primary particle concentrations decreased more
      relative to secondary ones. This is also supported by the analysis of the
      speciation data which showed that downward trends of primary pollutants including
      black carbon were stronger than those of secondary pollutants including sulfate.
      Furthermore, this study found that ambient primary pollutants decreased at the
      same rate as their respective source emissions. This was not the case for
      secondary pollutants which decreased at a slower rate than that of their
      precursor emissions. This indicates that concentrations of secondary pollutants
      depend not only on the primary emissions but also on the availability of
      atmospheric oxidants which might not change during the study period. This novel
      approach of investigating spatially varying concentration trends, in combination
      with ground PM2.5 species trends, can be of substantial regulatory importance.

PMID- 24906077
TI  - Deep-ultraviolet transparent phosphates RbBa2(PO3)5 and Rb2Ba3(P2O7)2 show
      nonlinear optical activity from condensation of [PO4](3-) units.
AB  - It is challenging to explore deep-ultraviolet (deep-UV) nonlinear optical (NLO)
      materials that can achieve a subtle balance between deep-UV transparency and high
      NLO activity. Known deep-UV NLO materials are almost exclusively limited to
      borates, except few newly discovered phosphates despite their small NLO
      activities. Here we report two asymmetric phosphates, RbBa2(PO3)5 (I) and
      Rb2Ba3(P2O7)2 (II), which feature [PO3]infinity chains and [P2O7](4-) dimers
      formed by condensation of [PO4](3-) units, respectively. Remarkably, I achieves
      the desired balance, with the shortest deep-UV absorption edge at 163 nm and the
      largest NLO activity of 1.4 * KDP (KH2PO4) in deep-UV NLO phosphates. According
      to first-principles calculations, the enhanced macroscopic SHG response of I can
      be attributed to the [PO3]infinity chains which exhibit significantly larger
      microscopic SHG coefficients as compared with the [P2O7](4-) dimers. 

PMID- 24906076
TI  - Molecular characterization of Thai Salmonella enterica serotype typhimurium and
      serotype 4,5,12:i:- reveals distinct genetic deletion patterns.
AB  - In order to better understand the relationship between Salmonella serotypes
      Typhimurium and its monophasic variant 4,5,12:i:- found in Thailand, a total of
      138 isolates from various sources were characterized using different molecular
      subtyping methods (i.e., pulsed-field gel electrophoresis [PFGE] and polymerase
      chain reaction [PCR]) and antibiotic resistance (AbR) patterns. PFGE revealed 52
      distinct band patterns among these isolates, 3 of which were shared between the
      two serotypes. PCR characterization of genomic deletion patterns reveals that
      Thai S. 4,5,12:i:- isolates contain a distinct deletion pattern in the fljAB
      region, which can be used as a specific genetic marker for primary identification
      of S. 4,5,12:i:- sources. AbR study shows that, among 50 representative serotype
      confirmed strains, 48.28% (14/29) of Salmonella Typhimurium and 90.48% (19/21) of
      4,5,12:i:- isolates are multidrug-resistant Salmonella as they are resistant to
      at least 3 antimicrobial categories. The AmpST pattern for resistance to
      ampicillin, streptomycin, and tetracycline was found in high proportions of
      Salmonella Typhimurium (10 of 29) and S. 4,5,12:i:- (15 of 21) isolates.

PMID- 24906078
TI  - Brief report: reduced expression of CD18 leads to the in vivo expansion of
      hematopoietic stem cells in mouse bone marrow.
AB  - Leukocyte adhesion deficiency type-I is a primary immunodeficiency caused by
      mutations in the ITGB2 gene (CD18 leukocyte integrin) which lead to defects in
      leukocyte extravasation. To investigate the role of CD18 in hematopoietic stem
      cell (HSC) biology, we have thoroughly characterized the HSCs of CD18
      Itgb2(tm1bay) hypomorphic mice (CD18(HYP) ) both by flow cytometry and using in
      vitro and in vivo transplantation assays. Flow cytometry analyses and cultures in
      methyl cellulose revealed that bone marrow (BM) from CD18(HYP) mice was enriched
      in hematopoietic precursors, mainly early quiescent short-term and long-term
      Hematopoietic progenitors cells. Strikingly, BM competition assays showed a
      progressive expansion of CD18(HYP) -derived hematopoiesis in recipient mice.
      Additionally, we provide evidence that this HSC expansion was not caused by an
      increased homing capacity of CD18(HYP) HSCs or by alterations in the
      hematopoietic environment of CD18(HYP) mice due to defects in neutrophils
      clearance. On the contrary, our data demonstrated that the reduced expression of
      CD18 causes a cell-autonomous expansion in the HSC compartment, thus revealing
      unexpected regulatory functions for CD18 in mouse HSCs.

PMID- 24906079
TI  - Quantification of Underestimation of Physical Activity During Cycling to School
      When Using Accelerometry.
AB  - BACKGROUND: Cycling to and from school is an important source of physical
      activity (PA) in youth but it is not captured by the dominant objective method to
      quantify PA. The aim of this study was to quantify the underestimation of
      objectively assessed PA caused by cycling when using accelerometry. METHODS:
      Participants were 20 children aged 11 to 14 years from a randomized controlled
      trial performed in 2011. Physical activity was assessed by accelerometry with the
      addition of heart rate monitoring during cycling to school. Global positioning
      system (GPS) was used to identify periods of cycling to school. RESULTS: Mean
      minutes of moderate-to-vigorous physical activity (MVPA) during round-trip
      commutes was 10.8 (95% CI: 7.1-16.6). Each kilometer of cycling meant an
      underestimation of 9314 (95% CI: 7719-11238) counts and 2.7 (95% CI: 2.1-3.5)
      minutes of MVPA. Adjusting for cycling to school increased estimates of MVPA/day
      by 6.0 (95% CI: 3.8-9.6) minutes. CONCLUSIONS: Cycling to and from school
      contribute substantially to levels of MVPA and to mean counts/min in children.
      This was not collected by accelerometers. Using distance to school in conjunction
      with self-reported cycling to school may be a simple tool to improve the
      methodology.

PMID- 24906080
TI  - Performance characterization of an abiotic and fluorescent-based continuous
      glucose monitoring system in patients with type 1 diabetes.
AB  - A continuous glucose monitoring (CGM) system consisting of a wireless,
      subcutaneously implantable glucose sensor and a body-worn transmitter is
      described and clinical performance over a 28 day implant period in 12 type 1
      diabetic patients is reported. The implantable sensor is constructed of a
      fluorescent, boronic-acid based glucose indicating polymer coated onto a
      miniaturized, polymer-encased optical detection system. The external transmitter
      wirelessly communicates with and powers the sensor and contains Bluetooth
      capability for interfacing with a Smartphone application. The accuracy of 19
      implanted sensors were evaluated over 28 days during 6 in-clinic sessions by
      comparing the CGM glucose values to venous blood glucose measurements taken every
      15 min. Mean absolute relative difference (MARD) for all sensors was 11.6 +/-
      0.7%, and Clarke error grid analysis showed that 99% of paired data points were
      in the combined A and B zones.

PMID- 24906081
TI  - Label-free alpha fetoprotein immunosensor established by the facile synthesis of
      a palladium-graphene nanocomposite.
AB  - In this study, we established a sensitive label-free immunosensor by palladium
      reduced graphene oxide (Pd-rGO), which was prepared by one-pot synthesis under
      the reduction of extra-injected CO gas. The Pd-rGO nanocomposite structure has
      been confirmed by TEM, SEM, X-ray diffraction, and UV-vis spectroscopy. The Pd
      rGO nanocomposite exhibited excellent stability in aqueous dispersion. The Pd-rGO
      based label-free electrochemical immunosensor was used for detection of the
      hepatocellular carcinoma (HCC) biomarker alpha fetoprotein (AFP). The
      immunosensor determination was based on the fact that due to the formation of
      antigen-antibody immunocomplex, the decreased response amperometric currents of
      H2O2 were directly proportional to the concentrations of AFP. The limit of
      detection of this immunosensor for AFP detection is 5 pg/mL, and is linear from
      0.01 to 12 ng/mL. The proposed immunosensor has been used to determine AFP in
      clinical serum samples with satisfactory results. This suggests the sensor may
      have great potential utility in the clinic.

PMID- 24906083
TI  - 4-Fluoro-3-nitrophenyl grafted gold electrode based platform for label free
      electrochemical detection of interleukin-2 protein.
AB  - A new platform based on 4-Fluoro-3-nitrophenyl (FNP) grafted gold disk electrode
      prepared via electrochemical reduction of 4-fluoro-3-nitrobenzene diazonium ion
      has been developed and utilized for biosensor fabrication. Anti-interleukin-2
      (anti-IL2) antibody has been covalently immobilized onto FNP/Au surface and
      utilized for label free electrochemical impedance based detection of cytokine
      IL2. FNP acts as a bridge (cross-linker) between gold surface and anti-IL2, where
      fluoro group of FNP undergoes nucleophilic substitution by amino group of
      biomolecule and results in its covalent immobilization. The immobilization
      process and fabricated electrode have been characterized using contact angle (CA)
      measurements, cyclic voltammetry (CV) and electrochemical impedance (EIS)
      technique. CV studies show that FNP grafted surface provides conductive surface
      for anti-IL2 immobilization. The EIS response of studies as a function of IL2
      concentrations exhibits a detection in linear range from 1 pg ml(-1) to 10 ng ml(
      1) with minimum detectable concentration of 1 pg ml(-1). The electrode has been
      found to be selective against other cytokine molecules.

PMID- 24906082
TI  - Design, development, and validation of an in-situ biosensor array for metabolite
      monitoring of cell cultures.
AB  - Conventional pharmaceutical processes involving cell culture growth are generally
      taken under control with expensive and long laboratory tests performed by direct
      sampling to evaluate quality. This traditional and well-established approach is
      just partially adequate in providing information about cell state.
      Electrochemical enzyme-based biosensors offer several advantages towards this
      application. In particular, they lend themselves to miniaturization and
      integration with cheap electronics. In the present work we go through the design,
      the development, and the validation of a self-contained device for the on-line
      measurement of metabolites in cell culture media. We microfabricated a sensing
      platform by using thin film technologies. We exploited electrodeposition to
      precisely immobilize carbon nanotubes and enzymes on miniaturized working
      electrodes. We designed and realized the electronics to perform the
      electrochemical measurements and an Android application to display the
      measurements on smartphones and tablets. In cell culture media glucose biosensor
      shows a sensitivity of 4.7 +/- 1.3 nA mM(-1)mm(-2) and a detection limit of 1.4mM
      (S/N = 3sigma), while for lactate biosensor the sensitivity is 12.2 +/- 3.8 nA
      mM(-1)mm(-2) and the detection limit is 0.3mM. The whole system was then
      validated by monitoring U937 cell line over 88 h. Metabolic trends were fully
      congruent with cell density and viability. This self-contained device is a
      promising tool to provide more detailed information on cell metabolism that are
      unprecedented in cell biology.

PMID- 24906084
TI  - Biosensor for selective detection of E. coli in spinach using the strong affinity
      of derivatized mannose with fimbrial lectin.
AB  - Escherichia coli (E. coli) contamination in foods and water resources represents
      a major threat for human health and the environment. This work exploits the
      strong affinity of mannose-containing oligosaccharides with the fimbrial lectin
      of E. coli to design novel biosensors. Modified carbohydrate ligands were
      synthesized by introducing phenyl residues and aliphatic chains to mannose via
      reductive amination in order to increase both the affinity and selectivity to E.
      coli compared to other pathogenic bacteria. The synthesized ligands include p
      thiolphenyl aminomannose (PTAM), p-carboxyphenyl aminomannose (PCAM), 1-deoxy-1
      aminomannopyranoside (DAMP), glucosamine and low molecular weight chitosan bonded
      to mercapto undecanoic acid. The structures of the ligands were confirmed using
      (1)H NMR and 1H, (13)C, COZY NMR, and ESI/MS. The ligands were immobilized onto
      gold electrodes and SPR surfaces using-mercaptoundecanoic acid with glycine as
      deactivating agent. Two detection mechanisms were tested: (i) metal-enhanced
      electrochemical detection (MED) and (ii) label-free surface plasmon resonance
      (SPR) detection. The introduction of phenyl residues and aliphatic side groups to
      the mannose-containing oligosaccharides produced extremely high affinity for E.
      coli with detection limit of 1 cfu/mL. The relative selectivity of these ligands
      for E. coli, Citrobacter freundii, Staphylococcus epidermidis were 100%, 2.6% and
      8.6% respectively. The biosensors were validated using spinach leaves at 3.0
      cfu/mL. The work provides a generic biosensor for other pathogenic bacteria by
      enabling multivalent binding, immediate recognition for pathogens as well as
      inhibition of bacterial growth.

PMID- 24906085
TI  - EIS-based biosensor for ultra-sensitive detection of TNF-alpha from non-diluted
      human serum.
AB  - Serum background is a critical issue for biosensor development as it interferes
      with the detection of target molecules and may give rise to false positive
      signal. We present here highly sensitive and selective TNF-alpha biosensor which
      is able to detect TNF-alpha from non-diluted human serum using magnetic bead
      coupled antibody and electrochemical impedance spectroscopy (EIS) techniques. The
      process is designed to detect TNF-alpha from human serum in three stages; (1)
      abundant protein backgrounds are depleted from the serum using magnetic bead
      coupled albumin and IgG antibodies, (2) after background depletion TNF-alpha is
      captured using magnetic bead coupled TNF-alpha antibody, and (3) the captured TNF
      alpha is eluted from the magnetic beads and measured using EIS technique in which
      comb structured gold microelectrodes array (CSGM) is utilized to enhance the
      detection sensitivity. The system is able to achieve the limit of detection (LOD)
      at 1 pg/ml (57 fM) and a linear relationship between increasing TNF-alpha
      concentrations and charge-transfer resistance in a dynamic range of 1-1000 pg/ml.

PMID- 24906086
TI  - A label-free fiber-optic Turbidity Affinity Sensor (TAS) for continuous glucose
      monitoring.
AB  - In this paper, we describe the concept of a novel implantable fiber-optic
      Turbidity Affinity Sensor (TAS) and report on the findings of its in-vitro
      performance for continuous glucose monitoring. The sensing mechanism of the TAS
      is based on glucose-specific changes in light scattering (turbidity) of a
      hydrogel suspension consisting of small particles made of crosslinked dextran
      (Sephadex G100), and a glucose- and mannose-specific binding protein -
      Concanavalin A (ConA). The binding of ConA to Sephadex particles results in a
      significant turbidity increase that is much greater than the turbidity
      contribution by the individual components. The turbidity of the TAS was measured
      by determining the intensity of light passing through the suspension enclosed
      within a small semi-permeable hollow fiber (OD: 220 MUm, membrane thickness: 20
      MUm, molecular weight cut-off: 10 kDa) using fiber optics. The intensity of
      measured light of the TAS was proportional to the glucose concentration over the
      concentration range from 50mg/dL to 400mg/dL in PBS and whole blood at 37 degrees
      C (R>0.96). The response time was approximately 4 min. The stability of the
      glucose response of the TAS decreased only slightly (by 20%) over an 8-day study
      period at 37 degrees C. In conclusion, this study demonstrated proof-of-concept
      of the TAS for interstitial glucose monitoring. Due to the large signal amplitude
      of the turbidity change, and the lack of need for wavelength-specific emission
      and excitation filters, a very small, robust and compact TAS device with an
      extremely short optical pathlength could be feasibly designed and implemented for
      in-vivo glucose monitoring in people with diabetes.

PMID- 24906087
TI  - A three-line lateral flow assay strip for the measurement of C-reactive protein
      covering a broad physiological concentration range in human sera.
AB  - The lateral flow assay (LFA) strip sensor possesses many advantages as a
      diagnostic device, including the capabilities of rapid, one-step assay
      performance, and high throughput production. A major limitation of the sensor,
      however, is its difficulty in measuring a broad concentration range of target
      proteins, including C-reactive protein (CRP), due to the "hook effect." In this
      study, we report the use of a three-line LFA strip sensor, adding an antigen line
      to the conventional two-line LFA sensor, for detecting CRP within a broad
      concentration range in human sera. We introduced an antigen line between test and
      control lines in the LFA sensor. The antigen line was formed by dispensing a CRP
      antibody solution followed by a CRP solution in nitrocellulose membrane. All
      other conditions were identical to those applied to the conventional LFA strip
      sensor. The CRP level in test samples was generated by data processing from the
      intensities of three lines. The strip sensor measured a linear detection range of
      CRP concentration from 1 ng/mL to 500 MUg/mL within 10 min, with a calculated
      detection range of 0.69 ng/mL-1.02 mg/mL. Using the developed three-line LFA
      sensor, 50 clinical samples were measured at a detection range of 0.4-84.7
      MUg/mL. This novel and easy-to-use CRP sensor can be a useful tool for rapid,
      sensitive, and cost-effective detection of a broad physiological concentration
      range of CRP capabilities that are vital for various diagnostic applications.

PMID- 24906088
TI  - Integrated electrochemical biosensor based on algal metabolism for water toxicity
      analysis.
AB  - An autonomous electrochemical biosensor with three electrodes integrated on the
      same silicon chip dedicated to the detection of herbicides in water was
      fabricated by means of silicon-based microfabrication technology. Platinum (Pt),
      platinum black (Pt Bl), tungsten/tungsten oxide (W/WO3) and iridium oxide
      (Pt/IrO2) working ultramicroelectrodes were developed. Ag/AgCl and Pt electrodes
      were used as reference and counter-integrated electrodes respectively. Physical
      vapor deposition (PVD) and electrodeposition were used for thin film deposition.
      The ultramicroelectrodes were employed for the detection of O2, H2O2 and pH
      related ions H3O(+)/OH(-), species taking part in photosynthetic and metabolic
      activities of algae. By measuring the variations in consumption-production rates
      of these electroactive species by algae, the quantity of herbicides present at
      trace level in the solution can be estimated. Fabricated ultramicroelectrodes
      were electrochemically characterized and calibrated. Pt Black
      ultramicroelectrodes exhibited the greatest sensitivity regarding O2 and H2O2
      detection while Pt/IrO2 ultramicroelectrodes were more sensitive for pH
      measurement compared to W/WO3 ultramicroelectrodes for pH measurement. Bioassays
      were then conducted to detect traces of Diuron herbicide in water samples by
      evaluating disturbances in photosynthetic and metabolic activities of algae
      caused by this herbicide. 

PMID- 24906089
TI  - Expression of serum toll-like receptor 9 and oxidative damage markers in benign
      and malignant breast diseases.
AB  - The intracellular redox environment plays an important role in the maintenance of
      proper cellular homeostasis and functions. Disturbances in redox equilibrium of
      cells result in pro-inflammatory conditions, and these inflammatory conditions
      can induce carcinogenesis or increase the malignant potential of the tumor.
      Oxidative stress or tissue damage can trigger toll-like receptor (TLR) family of
      receptors that are involved in altering the innate immune system. The present
      study was aimed at evaluating the level of oxidative damage markers in breast
      diseases by measuring the 8-hydroxydeoxyguanosine (8-OHdG), protein carbonyl
      (PC), malondialdehyde (MDA), and total antioxidant status (TAS) alterations in
      relation to expression of TLR-9. A significant increase in the level of oxidative
      damage markers was observed in breast carcinoma patients in comparison to benign
      and normal controls, which was accompanied by a significant decrease in TAS and
      expression of TLR-9 concentrations. 8-OHdG, PC, and MDA were negatively
      correlated with expression of TLR-9 and TAS levels. Altered levels of biomarkers
      of oxidative stress and TLR-9 among the malignant, benign, and controls suggest a
      correlation of oxidative stress and TLR signaling in the progression of disease
      in breast carcinoma patients. Receiver operating characteristic analysis depicts
      that expression of TLR-9 is a good indicator for distinguishing cancer patients
      from benign and normal controls. High accuracy, specificity, and sensitivity of
      oxidative stress markers and expression of TLR-9 can be used as discriminatory
      marker/s for efficient diagnosis. 

PMID- 24906090
TI  - Sp1 is necessary for gene activation of Adamts17 by estrogen.
AB  - Adamts17 is a member of a family of secreted metalloproteinases. In this report,
      we show that knockdown of Adamts17 expression induces apoptosis and inhibits
      breast cancer cell growth. Adamts17 expression can rapidly be induced by
      estrogens. siRNA knockdown of Sp1 or Myc demonstrated that Sp1 is required to
      induce Adamts17 gene expression in response to estrogen. Moreover, reporter
      assays showed that the proximal promoter and the upstream sequences were not
      capable of conferring estrogen responsiveness, suggesting that Sp1 elements may
      be located in the downstream intronic region. We further demonstrated that Sp1
      and Myc binding in the proximal promoter region contributed to the Adamts17 basal
      expression. Furthermore, histone deacetylase (HDAC) and methylase inhibitors also
      induced Adamts17 expression, indicating that epigenetic alterations, such as
      aberrant HDAC and/or methylation are associated with dysregulated Adamts17
      expression. By meta-analysis using Oncomine microarray data, we found that higher
      Adamts17 expression is found in several human cancer cell subtypes, especially in
      breast ductal carcinoma. Moreover, we found that there is an inverse correlation
      between higher Adamts17 expression and patients' survival. Our study suggests
      that Adamts17 may support breast cancer cell growth and survival.

PMID- 24906091
TI  - Novel application of Hemospray to achieve hemostasis in post-variceal banding
      esophageal ulcers that are actively bleeding.

PMID- 24906092
TI  - Asymptomatic colonic spirochetosis with severe inflammation on endoscopy.

PMID- 24906093
TI  - Potential utility of double-balloon enteroscopy for the diagnosis and evaluation
      of gastrointestinally mediated allergy.

PMID- 24906094
TI  - Single-balloon endoscopy to remove a migrated esophageal stent in the small
      bowel.

PMID- 24906095
TI  - Novel use of a self-expanding metal stent for an esophageal stricture after
      radiofrequency ablation treatment of Barrett's esophagus.

PMID- 24906096
TI  - Pancreatic metastasis from gastric carcinoma diagnosed by endoscopic ultrasound
      guided fine-needle aspiration.

PMID- 24906097
TI  - Extensive dabigatran-induced exfoliative esophagitis harboring squamous cell
      carcinoma.

PMID- 24906098
TI  - Rendezvous technique: double-balloon endoscopy and SpyGlass direct visualization
      system in a patient with severe stenosis of a choledochojejunal anastomosis.

PMID- 24906099
TI  - A case of pyogenic granuloma of the cecum treated by endoscopic resection.

PMID- 24906100
TI  - Acute esophageal necrosis: possible association with terlipressin.

PMID- 24906101
TI  - Duodenal perforation as a consequence of biliary stent migration can occur
      regardless of stent type or duration.

PMID- 24906102
TI  - Endoscopic removal of a proximally migrated pancreatic stent using a gooseneck
      snare.

PMID- 24906103
TI  - Delayed successful treatment of iatrogenic colon perforation using an over-the
      scope clip.

PMID- 24906104
TI  - Retroperitoneal schwannoma diagnosed by endoscopic ultrasound-guided fine-needle
      aspiration.

PMID- 24906105
TI  - ClearPath: a new method for fast and simple drainage of a perianastomotic
      abscess.

PMID- 24906107
TI  - Atomic Auger Doppler effects upon emission of fast photoelectrons.
AB  - Studies of photoemission processes induced by hard X-rays including production of
      energetic electrons have become feasible due to recent substantial improvement of
      instrumentation. Novel dynamical phenomena have become possible to investigate in
      this new regime. Here we show a significant change in Auger emission following 1s
      photoionization of neon, which we attribute to the recoil of the Ne ion induced
      by the emission of a fast photoelectron. Because of the preferential motion of
      the ionized Ne atoms along two opposite directions, an Auger Doppler shift is
      revealed, which manifests itself as a gradual broadening and doubling of the
      Auger spectral features. This Auger Doppler effect should be a general phenomenon
      in high-energy photoemission of both isolated atoms and molecules, which will
      have to be taken into account in studies of other recoil effects such as
      vibrational or rotational recoil in molecules, and may also have consequences in
      measurements in solids. 

PMID- 24906106
TI  - Molecular systems pharmacology: isoelectric focusing signature of protein kinase
      Cdelta provides an integrated measure of its modulation in response to ligands.
AB  - Protein kinase C (PKC), a validated therapeutic target for cancer chemotherapy,
      provides a paradigm for assessing structure-activity relations, where ligand
      binding has multiple consequences for a target. For PKC, ligand binding controls
      not only PKC activation and multiple phosphorylations but also subcellular
      localization, affecting subsequent signaling. Using a capillary isoelectric
      focusing immunoassay system, we could visualize a high resolution isoelectric
      focusing signature of PKCdelta upon stimulation by ligands of the phorbol ester
      and bryostatin classes. Derivatives that possessed different physicochemical
      characteristics and induced different patterns of biological response generated
      different signatures. Consistent with different patterns of PKCdelta localization
      as one factor linked to these different signatures, we found different signatures
      for activated PKCdelta from the nuclear and non-nuclear fractions. We conclude
      that the capillary isoelectric focusing immunoassay system may provide a window
      into the integrated consequences of ligand binding and thus afford a powerful
      platform for compound development. 

PMID- 24906108
TI  - Association of plasma interleukin-18 levels and polymorphisms in interleukin-18
      gene with outcomes of hepatitis C virus infections: a meta-analysis.
AB  - Several polymorphisms in the interleukin-18 (IL-18) gene and plasma IL-18 levels
      have been reported to influence hepatitis C virus (HCV) infection. However, the
      published findings have been conflicting. We conducted meta-analyses of
      randomized, controlled trials to address the association of IL-18 polymorphisms
      and plasma IL-18 levels and the outcomes of HCV infection. The results showed
      that there was no evidence for an association between the HCV infections and the
      polymorphisms genotypes of IL-18. However, plasma IL-18 levels were found higher
      in HCV infection patients than in healthy controls. The pooled SMD was 2.911(95%
      CI 2.556-3.265, z = 16.09, P < 0.001). 

PMID- 24906109
TI  - The development of automated patch clamp assays for canonical transient receptor
      potential channels TRPC3, 6, and 7.
AB  - The canonical transient receptor potential channel subfamily (TRPC3, TRPC6, and
      TRPC7) contains Ca(2+) permeable non-selective cation channels that are widely
      expressed in a variety of tissues. There is increasing evidence implicating TRPC
      channels, particularly TRPC3 and 6, in physiological and pathophysiological
      processes, eliciting interest in these channels as novel drug targets.
      Electrophysiology remains a benchmark technique for measuring ion channel
      function and accurately determining the pharmacological effects of compounds. In
      this report we describe the development of TRPC inhibitor assays on 2 automated
      planar patch clamp platforms-the IonWorks((r)) QuattroTM and QPatch((r)) systems.
      To enable activation of TRPC channels by carbachol, Chinese Hamster Ovary-K1
      cells stably expressing the muscarinic M3 receptor were transduced with human
      TRPC3, TRPC6, or TRPC7 using BacMam viruses. TRPC3, 6, and 7 currents could be
      recorded on both platforms. However, the design of each platform limits which
      assay parameters can be recorded. Due to its continuous recording capabilities,
      the QPatch can capture both the activation and decay of the response. However,
      the transient nature of TRPC channels, the inability to reactivate and the large
      variation in peak currents limits the ability to develop assays for compound
      screening. The IonWorks Quattro, due to its discontinuous sampling, did not fully
      capture the peak of TRPC currents. However, due to the ability of the IonWorks
      Quattro to record from 64 cells per well, the variation from well to well was
      sufficiently reduced allowing for the development of medium-throughput screening
      assays.

PMID- 24906110
TI  - Bispidine dioxotetraaza macrocycles: a new class of bispidines for (64)Cu PET
      imaging.
AB  - The three new dioxo-tetraazamacrocyclic ligands with a fused, very rigid
      bispidine (3,7-diazabicyclo[3.3.1]nonane) group connecting the two tertiary amine
      donors, and ethyl, propyl, or benzene groups connecting the two amide donors are
      highly preorganized and lead to very stable, uncharged Cu(II) complexes. Solution
      spectroscopy and solid state structures indicate that these are square pyramidal
      with a solvent molecule occupying the apical position. Cyclic voltammetry defines
      a reversible Cu(III/II) couple and a strongly negative irreversible Cu(II/I)
      couple (ca. -2 V vs Fc/Fc(+)), indicating that the Cu(II) complexes are very
      stable in solution. This is supported by superoxide dismutase (SOD) and human
      serum challenge experiments as well as the biodistribution, which all show that
      the benzene-based ligand has the highest in vitro and in vivo stability and that
      this was expected on the basis of the macrocycle ring size and shape and the
      highest degree of preorganization. This ligand is easy to functionalize for a
      possible coupling to biological vector molecules and/or fluorescence markers for
      PET (positron emission tomography) and multimodal imaging (i.e., PET and optical
      imaging). 

PMID- 24906111
TI  - Diversity of HIV/AIDS epidemic in China: a result from hierarchical clustering
      analysis and spatial autocorrelation analysis.
AB  - OBJECTIVE: To find out the diversity of HIV/AIDS epidemic among different areas
      in China according to their varied epidemic characteristics. DESIGN AND METHODS:
      Seventeen provincial variables, generated from original HIV/AIDS epidemic data
      and socioeconomic indicators to indicate HIV/AIDS epidemic characteristics, were
      introduced to hierarchical clustering analysis to form subepidemic areas. Then
      spatial autocorrelation analysis was applied to show the clustering distribution
      of cases from different most-at-risk populations. RESULTS: Three HIV/AIDS
      subepidemic areas (A, B, C) were formed, each of which was further divided into
      two clusters, showing the diversity of HIV/AIDS epidemic in China. A1 was the
      earliest and severest HIV/AIDS epidemic area and occupied 37% hotspot counties.
      The epidemic in A1 was driven by IDU in its early period and heterosexual
      transmission later. Henan, the only province in A2, characterized by its HIV/AIDS
      epidemic among former plasma donors during the early 1990s, presented strong
      spatial clustering of blood/plasma transmission occupying 80% blood/plasma
      hotspots. The epidemic within B3, located in southwest China, was driven by IDU
      and heterosexual populations, and recently by MSM. The epidemic within B4,
      covering all four municipalities, had been largely spread among MSM since 2005.
      B3 and B4 occupied 76% MSM hotspots. For C5 and C6, only sporadic HIV/AIDS
      infections occurred in the last years among former plasma donors and heterosexual
      populations, whereas the prevalence among MSM had been increasing. CONCLUSION:
      China's different HIV/AIDS subepidemic areas had obvious diversity of affected
      populations, which should be considered when determining prevention policies.

PMID- 24906113
TI  - Three Novel Haplotypes of Theileria bicornis in Black and White Rhinoceros in
      Kenya.
AB  - Piroplasms, especially those in the genera Babesia and Theileria, have been found
      to naturally infect rhinoceros. Due to natural or human-induced stress factors
      such as capture and translocations, animals often develop fatal clinical
      piroplasmosis, which causes death if not treated. This study examines the genetic
      diversity and occurrence of novel Theileria species infecting both black and
      white rhinoceros in Kenya. Samples collected opportunistically during routine
      translocations and clinical interventions from 15 rhinoceros were analysed by
      polymerase chain reaction (PCR) using a nested amplification of the small subunit
      ribosomal RNA (18S rRNA) gene fragments of Babesia and Theileria. Our study
      revealed for the first time in Kenya the presence of Theileria bicornis in white
      (Ceratotherium simum simum) and black (Diceros bicornis michaeli) rhinoceros and
      the existence of three new haplotypes: haplotypes H1 and H3 were present in white
      rhinoceros, while H2 was present in black rhinoceros. No specific haplotype was
      correlated to any specific geographical location. The Bayesian inference 50%
      consensus phylogram recovered the three haplotypes monophyleticly, and Theileria
      bicornis had very high support (BPP: 0.98). Furthermore, the genetic p
      uncorrected distances and substitutions between T. bicornis and the three
      haplotypes were the same in all three haplotypes, indicating a very close genetic
      affinity. This is the first report of the occurrence of Theileria species in
      white and black rhinoceros from Kenya. The three new haplotypes reported here for
      the first time have important ecological and conservational implications,
      especially for population management and translocation programs and as a means of
      avoiding the transport of infected animals into non-affected areas. 

PMID- 24906114
TI  - jqcML: an open-source java API for mass spectrometry quality control data in the
      qcML format.
AB  - The awareness that systematic quality control is an essential factor to enable
      the growth of proteomics into a mature analytical discipline has increased over
      the past few years. To this aim, a controlled vocabulary and document structure
      have recently been proposed by Walzer et al. to store and disseminate quality
      control metrics for mass-spectrometry-based proteomics experiments, called qcML.
      To facilitate the adoption of this standardized quality control routine, we
      introduce jqcML, a Java application programming interface (API) for the qcML data
      format. First, jqcML provides a complete object model to represent qcML data.
      Second, jqcML provides the ability to read, write, and work in a uniform manner
      with qcML data from different sources, including the XML-based qcML file format
      and the relational database qcDB. Interaction with the XML-based file format is
      obtained through the Java Architecture for XML Binding (JAXB), while generic
      database functionality is obtained by the Java Persistence API (JPA). jqcML is
      released as open-source software under the permissive Apache 2.0 license and can
      be downloaded from https://bitbucket.org/proteinspector/jqcml . 

PMID- 24906112
TI  - Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope
      specificity, T-cell receptor clonotype usage and antigen load.
AB  - OBJECTIVES: Although CD8+ T cells play a critical role in the control of HIV-1
      infection,their antiviral efficacy can be limited by antigenic variation and
      immune exhaustion.The latter phenomenon is characterized by the upregulation of
      multiple inhibitory receptors, such as programmed death-1 (PD-1), CD244 and
      lymphocyte activation gene-3 (LAG-3), which modulate the functional capabilities
      of CD8+ T cells. DESIGN AND METHODS: Here, we used an array of different human
      leukocyte antigen(HLA)-B*15:03 and HLA-B*42:01 tetramers to characterize
      inhibitory receptor expression as a function of differentiation on HIV-1-specific
      CD8+ T-cell populations(n = 128) spanning 11 different epitope targets. RESULTS:
      Expression levels of PD-1, but not CD244 or LAG-3, varied substantially across
      epitope specificities both within and between individuals. Differential
      expression of PD-1 on T-cell receptor (TCR) clonotypes within individual HIV-1
      specific CD8+ T-cell populations was also apparent, independent of clonal
      dominance hierarchies. Positive correlations were detected between PD-1
      expression and plasma viral load, which were reinforced by stratification for
      epitope sequence stability and dictated by effector memory CD8+ T cells.
      CONCLUSION: Collectively, these data suggest that PD-1 expression on HIV-1
      specific CD8+ T cells tracks antigen load at the level of epitope specificity and
      TCR clonotype usage. These findings are important because they provide evidence
      that PD-1 expression levels are influenced by peptide/HLA class I antigen
      exposure.

PMID- 24906115
TI  - Using the MMPI-2-RF to discriminate psychometrically identified schizotypic
      college students from a matched comparison sample.
AB  - This study investigates the extent to which the Minnesota Multiphasic Personality
      Inventory-2 Restructured Form (MMPI-2-RF) profiles of 52 individuals making up a
      psychometrically identified schizotypes (SZT) sample could be successfully
      discriminated from the protocols of 52 individuals in a matched comparison (MC)
      sample. Replication analyses were performed with an additional 53 pairs of SZT
      and MC participants. Results showed significant differences in mean T-score
      values between these 2 groups across a variety of MMPI-2-RF scales. Results from
      discriminant function analyses indicate that schizotypy can be predicted
      effectively using 4 MMPI-2-RF scales and that this method of classification held
      up on replication. Additional results demonstrated that these MMPI-2-RF scales
      nominally outperformed MMPI-2 scales suggested by previous research as being
      indicative of schizophrenia liability. Directions for future research with the
      MMPI-2-RF are suggested. 

PMID- 24906116
TI  - The crude skin secretion of the pepper frog Leptodactylus labyrinthicus is rich
      in metallo and serine peptidases.
AB  - Peptidases are ubiquitous enzymes involved in diverse biological processes.
      Fragments from bioactive peptides have been found in skin secretions from frogs,
      and their presence suggests processing by peptidases. Thus, the aim of this work
      was to characterize the peptidase activity present in the skin secretion of
      Leptodactylus labyrinthicus. Zymography revealed the presence of three bands of
      gelatinase activity of approximately 60 kDa, 66 kDa, and 80 kDa, which the first
      two were calcium-dependent. These three bands were inhibited either by
      ethylenediaminetetraacetic acid (EDTA) and phenathroline; thus, they were
      characterized as metallopeptidases. Furthermore, the proteolytic enzymes
      identified were active only at pH 6.0-10.0, and their activity increased in the
      presence of CHAPS or NaCl. Experiments with fluorogenic substrates incubated with
      skin secretions identified aminopeptidase activity, with cleavage after leucine,
      proline, and alanine residues. This activity was directly proportional to the
      protein concentration, and it was inhibited in the presence of metallo and serine
      peptidase inhibitors. Besides, the optimal pH for substrate cleavage was
      determined to be 7.0-8.0. The results of the in gel activity assay showed that
      all substrates were hydrolyzed by a 45 kDa peptidase. Gly-Pro-AMC was also
      cleaved by a peptidase greater than 97 kDa. The data suggest the presence of
      dipeptidyl peptidases (DPPs) and metallopeptidases; however, further research is
      necessary. In conclusion, our work will help to elucidate the implication of
      these enzymatic activities in the processing of the bioactive peptides present in
      frog venom, expanding the knowledge of amphibian biology. 

PMID- 24906118
TI  - An Albanian open source telemedicine platform.
AB  - INTRODUCTION: The use of open source technologies to create collaboration
      platforms can produce huge advantages with small investment. MATERIALS AND
      METHODS: We set up a telemedicine network for a healthcare district with typical
      centralization issues of developing countries. Our network was built using
      broadband Internet connection, and the digital divide in rural areas was reduced
      by means of wireless Internet connection. A software infrastructure was deployed
      on the network to implement the collaboration platform among different healthcare
      facilities. RESULTS: We obtained an integrated platform with modest investment in
      hardware and operating systems and no costs for application software. Messaging,
      content management, information sharing, and videoconferencing are among the
      available services of the infrastructure. Furthermore, open source software is
      managed and continuously updated by active communities, making it possible to
      obtain systems similar to commercial ones in terms of quality and reliability.
      CONCLUSIONS: As the use of free software in public administration is being widely
      promoted across the European Union, our experience may provide an example to
      implement similar infrastructures in the field of healthcare and welfare.

PMID- 24906117
TI  - The need for randomization in animal trials: an overview of systematic reviews.
AB  - BACKGROUND AND OBJECTIVES: Randomization, allocation concealment, and blind
      outcome assessment have been shown to reduce bias in human studies. Authors from
      the Collaborative Approach to Meta Analysis and Review of Animal Data from
      Experimental Studies (CAMARADES) collaboration recently found that these features
      protect against bias in animal stroke studies. We extended the scope the work
      from CAMARADES to include investigations of treatments for any condition.
      METHODS: We conducted an overview of systematic reviews. We searched Medline and
      Embase for systematic reviews of animal studies testing any intervention (against
      any control) and we included any disease area and outcome. We included reviews
      comparing randomized versus not randomized (but otherwise controlled), concealed
      versus unconcealed treatment allocation, or blinded versus unblinded outcome
      assessment. RESULTS: Thirty-one systematic reviews met our inclusion criteria: 20
      investigated treatments for experimental stroke, 4 reviews investigated
      treatments for spinal cord diseases, while 1 review each investigated treatments
      for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis,
      Parkinson's disease, and treatments used in emergency medicine. In our sample 29%
      of studies reported randomization, 15% of studies reported allocation
      concealment, and 35% of studies reported blinded outcome assessment. We pooled
      the results in a meta-analysis, and in our primary analysis found that failure to
      randomize significantly increased effect sizes, whereas allocation concealment
      and blinding did not. In our secondary analyses we found that randomization,
      allocation concealment, and blinding reduced effect sizes, especially where
      outcomes were subjective. CONCLUSIONS: Our study demonstrates the need for
      randomization, allocation concealment, and blind outcome assessment in animal
      research across a wide range of outcomes and disease areas. Since human studies
      are often justified based on results from animal studies, our results suggest
      that unduly biased animal studies should not be allowed to constitute part of the
      rationale for human trials.

PMID- 24906119
TI  - Does temperature-mediated reproductive success drive the direction of species
      displacement in two invasive species of leafminer fly?
AB  - Liriomyza sativae and L. trifolii (Diptera: Agromyzidae) are two highly invasive
      species of leafmining flies, which have become established as pests of
      horticultural crops throughout the world. In certain regions where both species
      have been introduced, L. sativae has displaced L. trifolii, whereas the opposite
      has occurred in other regions. These opposing outcomes suggest that neither
      species is an inherently superior competitor. The regions where these
      displacements have been observed (southern China, Japan and western USA) are
      climatically different. We determined whether temperature differentially affects
      the reproductive success of these species and therefore if climatic differences
      could affect the outcome of interspecific interactions where these species are
      sympatric. The results of life table parameters indicate that both species can
      develop successfully at all tested temperatures (20, 25, 31, 33 degrees C). L.
      sativae had consistently higher fecundities at all temperatures, but L. trifolii
      developed to reproductive age faster. Age-stage specific survival rates were
      higher for L. sativae at low temperatures, but these were higher for L. trifolii
      at higher temperatures. We then compared the net reproductive rates (R0) for both
      species in pure and mixed cultures maintained at the same four constant
      temperatures. Both species had significantly lower net reproductive rates in
      mixed species cultures compared with their respective pure species cultures,
      indicating that both species are subject to intense interspecific competition.
      Net reproductive rates were significantly greater for L. sativae than for L.
      trifolii in mixed species groups at the lower temperatures, whereas the opposite
      occurred at the higher temperature. Therefore, interactions between the species
      are temperature dependent and small differences could shift the competitive
      balance between the species. These temperature mediated effects may contribute to
      the current ongoing displacement of L. sativae by the more recent invader L.
      trifolii in warm climatic areas of China. 

PMID- 24906120
TI  - Nesfatin-1 influences the excitability of glucosensing neurons in the dorsal
      vagal complex and inhibits food intake.
AB  - Nesfatin-1 is a recently discovered metabolic peptide hormone that decreases food
      intake after lateral, third, or fourth brain ventricle; cisterna magna; or
      paraventricular nucleus (PVN) injection in ad libitum fed rats. Additional micro
      injection studies will improve the understanding of how nesfatin-1 acts on the
      brain and define specific nuclei responsive to nesfatin-1, which will provide
      insight on its effects on food intake. We evaluated how nesfatin-1 injection into
      the dorsal vagal complex (DVC) modulates food intake response in rats during the
      dark phase. Consistent with previous observations, nesfatin-1-injected rats
      significantly reduced cumulative food intake over a 5-h period in rats. Chronic
      administration of nesfatin-1 into the DVC reduced body weight gain over a 10-day
      period. Because glucosensing neurons in the DVC are involved in glucoprivic
      feeding and homeostatic control of blood glucose, we examined the effect of
      nesfatin-1 on the excitability of DVC glucosensing neurons. Nesfatin-1 inhibited
      most of the glucose-inhibitory (GI) neurons and excited most of the glucose
      excitatory (GE) neurons in the DVC. Current-clamp electrophysiology recordings
      from DVC glucosensing neurons in slice preparation showed that bath applied
      nesfatin-1(10 nM) increased the firing frequency of GE neurons and inhibited the
      firing rate of GI-neurons. Nesfatin-1 inhibited 88.9% (16/18) of gastric
      distension inhibitory (GD-INH) neurons and excited 76.2% (32/42) of gastric
      distension excitatory (GD-EXC) neurons. Thus, nesfatin-1 may control food intake
      by modulating the excitability of glucosensing neurons in the DVC. 

PMID- 24906121
TI  - A curated census of autophagy-modulating proteins and small molecules: candidate
      targets for cancer therapy.
AB  - Autophagy, a programmed process in which cell contents are delivered to lysosomes
      for degradation, appears to have both tumor-suppressive and tumor-promoting
      functions; both stimulation and inhibition of autophagy have been reported to
      induce cancer cell death, and particular genes and proteins have been associated
      both positively and negatively with autophagy. To provide a basis for incisive
      analysis of those complexities and ambiguities and to guide development of new
      autophagy-targeted treatments for cancer, we have compiled a comprehensive,
      curated inventory of autophagy modulators by integrating information from
      published siRNA screens, multiple pathway analysis algorithms, and extensive,
      manually curated text-mining of the literature. The resulting inventory includes
      739 proteins and 385 chemicals (including drugs, small molecules, and
      metabolites). Because autophagy is still at an early stage of investigation, we
      provide extensive analysis of our sources of information and their complex
      relationships with each other. We conclude with a discussion of novel strategies
      that could potentially be used to target autophagy for cancer therapy. 

PMID- 24906122
TI  - To do or not to do; dilemma of intra-arterial revascularization in acute ischemic
      stroke.
AB  - BACKGROUND: There has still been lack of evidence for definite imaging criteria
      of intra-arterial revascularization (IAR). Therefore, IAR selection is left
      largely to individual clinicians. In this study, we sought to investigate the
      overall agreement of IAR selection among different stroke clinicians and factors
      associated with good agreement of IAR selection. METHODS: From the prospectively
      registered data base of a tertiary hospital, we identified consecutive patients
      with acute ischemic stroke. IAR selection based on the provided magnetic
      resonance imaging (MRI) results and clinical information were independently
      performed by 5 independent stroke physicians currently working at 4 different
      university hospitals. MRI results were also reviewed by 2 independent experienced
      neurologists blinded to clinical data and physicians' IAR selection. The Alberta
      Stroke Program Early Computed Tomography Score (ASPECTS) was calculated on
      initial DWI and MTT. We arbitrarily used ASPECTS differences between DWI and MTT
      (D-M ASPECTS) to quantitatively evaluate mismatch. RESULTS: The overall
      interobserver agreement of IAR selection was fair (kappa = 0.398). In patients
      with DWI-ASPECTS >6, interobserver agreement was moderate to substantial (0.398
      0.620). In patients with D-M ASPECTS >4, interobserver agreement was moderate to
      almost perfect (0.532-1.000). Patients with higher DWI or D-M ASPECTS had better
      agreement of IAR selection. CONCLUSION: Our study showed that DWI-ASPSECTS >6 and
      D-M ASPECTS >4 had moderate to substantial agreement of IAR selection among
      different stroke physicians. However, there is still poor agreement as to whether
      IAR should not be performed in patients with lower DWI and D-M ASPECTS.

PMID- 24906123
TI  - Effects of hot-water extract of banana (Musa acuminata) fruit's peel on the
      antibacterial activity, and anti-hypothermal stress, immune responses and disease
      resistance of the giant freshwater prawn, Macrobrachium rosenbegii.
AB  - The hot-extracts isolated from fruit's peel of banana, Musa acuminata, was
      evaluated on the antibacterial activity to pathogens from aquatic animals, and
      immunostimulating potential, disease resistance and anti-hypothermal stress in
      giant freshwater prawn, Macrobrachium rosenbergii through injection
      administration. The banana peel extract (BPE) showed good activity against 1 Gram
      positive and 3 Gram-negative pathogens, including Lactococcus garvieae,
      Photobacteria damsella, Vibrio alginolyticus and Vibrio parahemolyticus
      especially in prawn pathogen of L. garvieae strain, which were carried out by a
      disk diffusion method. Prawn received BPE via injection administration at 1-6 MUg
      (g prawn)(-1) significantly increased total haemocyte count (THC), hyaline cell
      (HC), granular cell (GC), phenoloxidase (PO) activity and phagocytic activity
      against L. garvieae from 3 to 6 days, and significantly increased clearance
      efficiency against L. garvieae and a significantly decreased coagulation time of
      prawn from 1 to 6 days. Prawn injected with BPE at 6.0 MUg (g prawn)(-1) for 6
      days showed significantly increased superoxide dismutase (SOD) activity, but
      significantly decreased respiratory bursts (RBs) of per haemocyte. Survival rates
      of M. rosenbergii injected with BPE at concentrations of 1, 3 and 6 MUg (g
      prawn)(-1) were significantly higher than those injected with saline control
      after challenge with L. garvieae for 4-6 days, and the respective relative
      survival percentages of prawn were 28.6%, 38.1%, and 47.8%, respectively at 6
      days. The sublethal time of prawns that had received saline and BPE at 1, 3 and 6
      MUg (g prawn)(-1) for 6 days and then were transferred from 28  degrees C to 14 
      degrees C were 69.4, 79.8, 83.6, and 90.2 h, respectively. It was concluded that
      the BPE can be used as the bacteriostat, and immunostimulant and physiological
      regulator for prawn through injection administration to enhance immunity,
      physiological responses, and resistance against L. garvieae.

PMID- 24906124
TI  - Induced systemic resistance by beneficial microbes.
AB  - Beneficial microbes in the microbiome of plant roots improve plant health.
      Induced systemic resistance (ISR) emerged as an important mechanism by which
      selected plant growth-promoting bacteria and fungi in the rhizosphere prime the
      whole plant body for enhanced defense against a broad range of pathogens and
      insect herbivores. A wide variety of root-associated mutualists, including
      Pseudomonas, Bacillus, Trichoderma, and mycorrhiza species sensitize the plant
      immune system for enhanced defense without directly activating costly defenses.
      This review focuses on molecular processes at the interface between plant roots
      and ISR-eliciting mutualists, and on the progress in our understanding of ISR
      signaling and systemic defense priming. The central role of the root-specific
      transcription factor MYB72 in the onset of ISR and the role of phytohormones and
      defense regulatory proteins in the expression of ISR in aboveground plant parts
      are highlighted. Finally, the ecological function of ISR-inducing microbes in the
      root microbiome is discussed. 

PMID- 24906125
TI  - Speciation in fungal and oomycete plant pathogens.
AB  - The process of speciation, by definition, involves evolution of one or more
      reproductive isolating mechanisms that split a single species into two that can
      no longer interbreed. Determination of which processes are responsible for
      speciation is important yet challenging. Several studies have proposed that
      speciation in pathogens is heavily influenced by host-pathogen dynamics and that
      traits that mediate such interactions (e.g., host mobility, reproductive mode of
      the pathogen, complexity of the life cycle, and host specificity) must lead to
      reproductive isolation and ultimately affect speciation rates. In this review, we
      summarize the main evolutionary processes that lead to speciation of fungal and
      oomycete plant pathogens and provide an outline of how speciation can be studied
      rigorously, including novel genetic/genomic developments. 

PMID- 24906126
TI  - The activation and suppression of plant innate immunity by parasitic nematodes.
AB  - Plant-parasitic nematodes engage in prolonged and intimate relationships with
      their host plants, often involving complex alterations in host cell morphology
      and function. It is puzzling how nematodes can achieve this, seemingly without
      activating the innate immune system of their hosts. Secretions released by
      infective juvenile nematodes are thought to be crucial for host invasion, for
      nematode migration inside plants, and for feeding on host cells. In the past,
      much of the research focused on the manipulation of developmental pathways in
      host plants by plant-parasitic nematodes. However, recent findings demonstrate
      that plant-parasitic nematodes also deliver effectors into the apoplast and
      cytoplasm of host cells to suppress plant defense responses. In this review, we
      describe the current insights in the molecular and cellular mechanisms underlying
      the activation and suppression of host innate immunity by plant-parasitic
      nematodes along seven critical evolutionary and developmental transitions in
      plant parasitism. 

PMID- 24906127
TI  - Virus infection cycle events coupled to RNA replication.
AB  - Replication, the process by which the genetic material of a virus is copied to
      generate multiple progeny genomes, is the central part of the virus infection
      cycle. For an infection to be productive, it is essential that this process is
      coordinated with other aspects of the cycle, such as translation of the viral
      genome, encapsidation, and movement of the genome between cells. In the case of
      positive-strand RNA viruses, this represents a particular challenge, as the
      infecting genome must not only be replicated but also serve as an mRNA for the
      production of the replication-associated proteins. In recent years, it has become
      apparent that in positive-strand RNA plant viruses all the aspects of the
      infection cycle are intertwined. This article reviews the current state of
      knowledge regarding replication-associated events in such viruses. 

PMID- 24906128
TI  - Novel insights into rice innate immunity against bacterial and fungal pathogens.
AB  - Rice feeds more than half of the world's population. Rice blast, caused by the
      fungal pathogen Magnaporthe oryzae, and bacterial blight, caused by the bacterial
      pathogen Xanthomonas oryzae pv. oryzae, are major constraints to rice production
      worldwide. Genome sequencing and extensive molecular analysis has led to the
      identification of many new pathogen-associated molecular patterns (PAMPs) and
      avirulence and virulence effectors in both pathogens, as well as effector targets
      and receptors in the rice host. Characterization of these effectors, host
      targets, and resistance genes has provided new insight into innate immunity in
      plants. Some of the new findings, such as the binding activity of X. oryzae
      transcriptional activator-like (TAL) effectors to specific rice genomic
      sequences, are being used for the development of effective disease control
      methods and genome modification tools. This review summarizes the recent progress
      toward understanding the recognition and signaling events that govern rice innate
      immunity. 

PMID- 24906129
TI  - Plant-parasitic nematode infections in rice: molecular and cellular insights.
AB  - Being one of the major staple foods in the world, and an interesting model
      monocot plant, rice (Oryza sativa L.) has recently received attention from
      molecular nematologists studying the cellular and molecular aspects of the
      interaction between this crop and plant-parasitic nematodes. In this review, we
      highlight recent advances in this field, with a focus on the best-studied root
      knot nematodes. Histological studies have revealed the cellular changes inside
      root-knot nematode-induced feeding sites, both in the compatible interaction with
      Oryza sativa and the incompatible interaction with the related species Oryza
      glaberrima. After comparing the published data from transcriptome analyses,
      mutant studies, and exogenous hormone applications, we provide a comprehensive
      model showing the role and interaction of plant hormone pathways in defense of
      this monocot crop against root nematodes, where jasmonate seems to play a key
      role. Finally, recent evidence indicates that effectors secreted from rice
      infecting nematodes can suppress plant defense. 

PMID- 24906130
TI  - The ABCs and 123s of bacterial secretion systems in plant pathogenesis.
AB  - Bacteria have many export and secretion systems that translocate cargo into and
      across biological membranes. Seven secretion systems contribute to pathogenicity
      by translocating proteinaceous cargos that can be released into the extracellular
      milieu or directly into recipient cells. In this review, we describe these
      secretion systems and how their complexities and functions reflect differences in
      the destinations, states, functions, and sizes of the translocated cargos as well
      as the architecture of the bacterial cell envelope. We examine the secretion
      systems from the perspective of pathogenic bacteria that proliferate within plant
      tissues and highlight examples of translocated proteins that contribute to the
      infection and disease of plant hosts. 

PMID- 24906131
TI  - Izumo meets Juno: preventing polyspermy in fertilization.

PMID- 24906132
TI  - A new Child-Turcotte-Pugh class 0 for patients with hepatocellular carcinoma:
      determinants, prognostic impact and ability to improve the current staging
      systems.
AB  - BACKGROUND/AIM: Majority of patients with hepatocellular carcinoma (HCC) belonged
      to Child-Turcotte-Pugh (CTP) class A. We aimed to identify a new class of
      patients with very well-preserved liver function and analyze its impact on
      outcome prediction, tumor staging and treatment allocation. METHODS: A total of
      2654 HCC patients were retrospectively analyzed. The prognostic ability was
      compared by the Akaike information criterion (AIC). RESULTS: The CTP class 0 was
      defined by fulfilling all criteria of albumin ?4 g/dL, bilirubin ?0.8 mg/dL,
      prothrombin time prolongation <0 seconds, no ascites and encephalopathy. A total
      of 23% of patients of CTP class A were reclassified as CTP class 0. Patients with
      CTP class 0 had a higher serum sodium level, lower serum creatinine, alanine
      aminotransferase, alpha-fetoprotein levels, shorter prothrombin time, better
      general well-being, smaller tumor burden with more solitary nodules, lower rates
      of vascular invasion, ascites formation, hepatic encephalopathy, more frequently
      treated with curative interventions and better Barcelona Clinic Liver Cancer
      (BCLC) stages (all p<0.001). In the Cox proportional hazards model, the adjusted
      hazard ratios for CTP class A, B and C were 1.739, 3.120 and 5.107, respectively,
      compared to class 0 (all p<0.001). Reassigning patients with CTP class 0, A, B, B
      and C to stage 0, A, B, C and D, respectively, provided the lowest AIC score
      among all BCLC-based models. CONCLUSIONS: The proposal of CTP class 0
      independently predicted better survival in HCC patients. Modification of tumor
      staging systems according to the modified CTP classification further enhances
      their prognostic ability.

PMID- 24906133
TI  - A study of the relationship between serum bile acids and propranolol
      pharmacokinetics and pharmacodynamics in patients with liver cirrhosis and in
      healthy controls.
AB  - The main objectives of the study were to determine the exposure and
      bioavailability of oral propranolol and to investigate their associations with
      serum bile acid concentration in patients with liver cirrhosis and in healthy
      controls. A further objective was to study the pharmacodynamics of propranolol.
      An open-label crossover study was performed to determine the pharmacokinetics and
      pharmacodynamics of propranolol after oral (40 mg) and intravenous (1 mg)
      administration as well as the concentration of total and individual fasting serum
      bile acids in 15 patients with liver cirrhosis and 5 healthy controls. After
      intravenous propranolol, patients showed a 1.8-fold increase in the area under
      the plasma concentration-time curve (AUC0-infinity), a 1.8-fold increase in
      volume of distribution and a 3-fold increase in the elimination half-life (mean
      +/- SEM: 641+/-100 vs. 205+/-43 minutes) compared to controls. After oral
      application, AUC0-infinity and elimination half-life of propranolol were
      increased 6- and 4-fold, respectively, and bioavailability 3-fold (83+/-8 vs.
      27+/-9.2%). Maximal effects on blood pressure and heart rate occurred during the
      first 4 and first 2 hours, respectively, after intravenous and oral application
      in both patients and controls. Total serum bile acid concentrations were higher
      in patients than controls (42+/-11 vs. 2.7+/-0.3 umol/L) and were linearly
      correlated with the serum chenodeoxycholic acid concentration. There was a linear
      correlation between the SBA concentration and propranolol oral AUC0-infinity in
      subjects not receiving interacting drugs (r2 = 0.73, n = 18). The bioavailability
      of and exposure to oral propranolol are increased in patients with cirrhosis.
      Fasting serum bile acid concentration may be helpful in predicting the exposure
      to oral propranolol in these patients. 

PMID- 24906134
TI  - Dual effects of alpha2 -adrenoceptors in modulating myogenic tone in sheep
      isolated internal anal sphincter.
AB  - BACKGROUND: The role of alpha-adrenoceptors in promoting continence through
      modulation of sphincter tone has focused primarily on the effects of alpha1 
      adrenoceptors. We have used three clinically available agents, which are
      selective for alpha2 -adrenoceptors, to investigate their role in contractile and
      neurogenic responses on the internal anal sphincter (IAS). METHODS: IAS strips,
      which had spontaneously generated tone, were used to investigate the contractile
      effect of lofexidine, brimonidine, and dexmedetomidine on muscle tone in the
      presence or absence of subtype selective antagonists. The effect of brimonidine
      on the magnitude and time course of neurogenic responses generated by electrical
      field stimulation (EFS) was also examined. The affinity of test compounds at
      alpha1 - and alpha2 -adrenoceptors was established by competition binding with
      [3H]-prazosin and [3H]-RX821002. KEY RESULTS: All agonists caused concentration
      dependent contraction of the IAS and lofexidine demonstrated an enantiomeric
      difference in potency with a 10-fold difference between the (-) and (+) isomers.
      Responses to lofexidine and dexmedetomidine were inhibited in the presence of the
      alpha1 -adrenoceptor selective antagonist prazosin, but not in the presence of
      RX811059 (alpha2 -adrenoceptor selective antagonist); brimonidine responses were
      inhibited by RX811059 and, to a lesser extent, by prazosin. Brimonidine affected
      both magnitude and duration of neurogenic responses, which was reversed in the
      presence of RX811059. CONCLUSIONS & INFERENCES: We conclude that alpha2 
      adrenoceptors can mediate contraction of IAS, although this effect is most
      evident with efficacious imidazoline agonists rather than the most selective
      ligand. In addition, this receptor subtype can directly inhibit noradrenergic
      contractile responses to EFS and, indirectly, enhance nitrergic relaxatory
      responses.

PMID- 24906135
TI  - Incomplete septal cirrhosis after high-dose methylprednisolone therapy and
      regression of liver injury.

PMID- 24906136
TI  - Cluster size statistic and cluster mass statistic: two novel methods for
      identifying changes in functional connectivity between groups or conditions.
AB  - Functional connectivity has become an increasingly important area of research in
      recent years. At a typical spatial resolution, approximately 300 million
      connections link each voxel in the brain with every other. This pattern of
      connectivity is known as the functional connectome. Connectivity is often
      compared between experimental groups and conditions. Standard methods used to
      control the type 1 error rate are likely to be insensitive when comparisons are
      carried out across the whole connectome, due to the huge number of statistical
      tests involved. To address this problem, two new cluster based methods--the
      cluster size statistic (CSS) and cluster mass statistic (CMS)--are introduced to
      control the family wise error rate across all connectivity values. These methods
      operate within a statistical framework similar to the cluster based methods used
      in conventional task based fMRI. Both methods are data driven, permutation based
      and require minimal statistical assumptions. Here, the performance of each
      procedure is evaluated in a receiver operator characteristic (ROC) analysis,
      utilising a simulated dataset. The relative sensitivity of each method is also
      tested on real data: BOLD (blood oxygen level dependent) fMRI scans were carried
      out on twelve subjects under normal conditions and during the hypercapnic state
      (induced through the inhalation of 6% CO2 in 21% O2 and 73%N2). Both CSS and CMS
      detected significant changes in connectivity between normal and hypercapnic
      states. A family wise error correction carried out at the individual connection
      level exhibited no significant changes in connectivity.

PMID- 24906138
TI  - Concurrent Generation of Ordinal and Normal Data.
AB  - The use of joint models that are capable of handling different data types is
      becoming increasingly popular in biopharmaceutical practice. Evaluation of
      various statistical techniques that have been developed for mixed data in
      simulated environments requires joint generation of multiple variables. In this
      article, we propose a unified framework for concurrently simulating ordinal and
      normal data given the marginal characteristics and correlation structure. We
      illustrate our technique in two simulation settings where we use artificial data
      as well as real depression score data from psychiatric research, demonstrating
      negligibly small deviations between the specified and empirically computed
      quantities. 

PMID- 24906137
TI  - The epigenetic regulator I-BET151 induces BIM-dependent apoptosis and cell cycle
      arrest of human melanoma cells.
AB  - Epigenetic changes are widespread in melanoma and contribute to the pathogenic
      biology of this disease. In the present study, we show that I-BET151, which
      belongs to a new class of drugs that target the BET family of epigenetic "reader"
      proteins, inhibits melanoma growth in vivo and induced variable degrees of
      apoptosis in a panel of melanoma cells. Apoptosis was caspase dependent and
      associated with G1 cell cycle arrest. All melanoma cells tested had increased
      levels of the BH3 proapoptotic protein BIM, which appeared to be regulated by the
      BRD2 BET protein and to some extent by BRD3. In contrast, knockdown experiments
      indicated that inhibition of BRD4 was associated with decreased levels of BIM.
      Apoptosis was dependent on BIM in some but not all cell lines, indicating that
      other factors were determinants of apoptosis, such as downregulation of
      antiapoptotic proteins revealed in gene expression arrays. G1 cell cycle arrest
      appeared to be mediated by p21 and resulted from inhibition of the BRD4 protein.
      The activity of BET protein inhibitors appears independent of the BRAF and NRAS
      mutational status of melanoma, and further studies to assess their therapeutic
      role in melanoma are warranted. 

PMID- 24906140
TI  - Estimating diagnostic test accuracies for Brachyspira hyodysenteriae accounting
      for the complexities of population structure in food animals.
AB  - For swine dysentery, which is caused by Brachyspira hyodysenteriae infection and
      is an economically important disease in intensive pig production systems
      worldwide, a perfect or error-free diagnostic test ("gold standard") is not
      available. In the absence of a gold standard, Bayesian latent class modelling is
      a well-established methodology for robust diagnostic test evaluation. In contrast
      to risk factor studies in food animals, where adjustment for within group
      correlations is both usual and required for good statistical practice, diagnostic
      test evaluation studies rarely take such clustering aspects into account, which
      can result in misleading results. The aim of the present study was to estimate
      test accuracies of a PCR originally designed for use as a confirmatory test,
      displaying a high diagnostic specificity, and cultural examination for B.
      hyodysenteriae. This estimation was conducted based on results of 239 samples
      from 103 herds originating from routine diagnostic sampling. Using Bayesian
      latent class modelling comprising of a hierarchical beta-binomial approach (which
      allowed prevalence across individual herds to vary as herd level random effect),
      robust estimates for the sensitivities of PCR and culture, as well as for the
      specificity of PCR, were obtained. The estimated diagnostic sensitivity of PCR
      (95% CI) and culture were 73.2% (62.3; 82.9) and 88.6% (74.9; 99.3),
      respectively. The estimated specificity of the PCR was 96.2% (90.9; 99.8). For
      test evaluation studies, a Bayesian latent class approach is well suited for
      addressing the considerable complexities of population structure in food animals.

PMID- 24906141
TI  - Eosinophils in fat: pink is the new brown.
AB  - Subcutaneous white adipose tissue can be induced to undergo "browning" and
      acquire thermogenic capacity in response to physiological stimuli such as cold
      exposure or exercise. In this issue of Cell, Qiu et al. and Rao et al.
      demonstrate that pink-staining eosinophils and alternatively activated
      macrophages play key roles in an immune cascade mediating this metabolic switch. 

PMID- 24906142
TI  - Delivering three punches to knockout intracellular bacteria.
AB  - Cytotoxic lymphocytes kill bacteria-infected cells, but the mechanisms at work
      remain unclear. Walch et al. show that these lymphocytes deliver a toxic
      molecular trio in a two-step process, penetrating first the infected cells and
      then delivering bactericidal granzymes into the intracytoplasmic bacteria. 

PMID- 24906143
TI  - Getting a grip on piRNA cluster transcription.
AB  - The generation of piRNAs from long primary transcripts requires specialized
      factors that distinguish these precursors from canonical RNA polymerase II
      transcripts. Mohn et al. and Zhang et al. provide evidence that in Drosophila
      melanogaster noncanonical transcription coupled with splicing inhibition
      differentiates piRNA precursors from mRNAs and ensures their correct processing. 

PMID- 24906144
TI  - A slow dance for microtubule acetylation.
AB  - Microtubules contribute to diverse cellular processes through balancing dynamic,
      short-lived and stable, long-lived populations. One way in which long-lived
      microtubules are marked is by posttranslational acetylation of alpha-tubulin by
      tubulin acetyltransferase (TAT). Szyk et al. now provide insight into TAT's
      mechanism of action and its unique time-stamping ability. 

PMID- 24906145
TI  - Applying "gold standards" to in-vitro-derived germ cells.
AB  - Germ cells are the ultimate stem cells, and reports of their in vitro derivation
      generate excitement due to potential applications in reproductive medicine. To
      date, there is no firm evidence that meiosis, the hallmark of gametogenesis, can
      be faithfully replicated outside of the gonad. We propose benchmarks for
      evaluating in vitro derivation of germ cells, facilitating realization of their
      potential.

PMID- 24906147
TI  - Meteorin-like is a hormone that regulates immune-adipose interactions to increase
      beige fat thermogenesis.
AB  - Exercise training benefits many organ systems and offers protection against
      metabolic disorders such as obesity and diabetes. Using the recently identified
      isoform of PGC1-alpha (PGC1-alpha4) as a discovery tool, we report the
      identification of meteorin-like (Metrnl), a circulating factor that is induced in
      muscle after exercise and in adipose tissue upon cold exposure. Increasing
      circulating levels of Metrnl stimulates energy expenditure and improves glucose
      tolerance and the expression of genes associated with beige fat thermogenesis and
      anti-inflammatory cytokines. Metrnl stimulates an eosinophil-dependent increase
      in IL-4 expression and promotes alternative activation of adipose tissue
      macrophages, which are required for the increased expression of the thermogenic
      and anti-inflammatory gene programs in fat. Importantly, blocking Metrnl actions
      in vivo significantly attenuates chronic cold-exposure-induced alternative
      macrophage activation and thermogenic gene responses. Thus, Metrnl links host
      adaptive responses to the regulation of energy homeostasis and tissue
      inflammation and has therapeutic potential for metabolic and inflammatory
      diseases.

PMID- 24906146
TI  - Development and applications of CRISPR-Cas9 for genome engineering.
AB  - Recent advances in genome engineering technologies based on the CRISPR-associated
      RNA-guided endonuclease Cas9 are enabling the systematic interrogation of
      mammalian genome function. Analogous to the search function in modern word
      processors, Cas9 can be guided to specific locations within complex genomes by a
      short RNA search string. Using this system, DNA sequences within the endogenous
      genome and their functional outputs are now easily edited or modulated in
      virtually any organism of choice. Cas9-mediated genetic perturbation is simple
      and scalable, empowering researchers to elucidate the functional organization of
      the genome at the systems level and establish causal linkages between genetic
      variations and biological phenotypes. In this Review, we describe the development
      and applications of Cas9 for a variety of research or translational applications
      while highlighting challenges as well as future directions. Derived from a
      remarkable microbial defense system, Cas9 is driving innovative applications from
      basic biology to biotechnology and medicine. 

PMID- 24906148
TI  - Eosinophils and type 2 cytokine signaling in macrophages orchestrate development
      of functional beige fat.
AB  - Beige fat, which expresses the thermogenic protein UCP1, provides a defense
      against cold and obesity. Although a cold environment is the physiologic stimulus
      for inducing beige fat in mice and humans, the events that lead from the sensing
      of cold to the development of beige fat remain poorly understood. Here, we
      identify the efferent beige fat thermogenic circuit, consisting of eosinophils,
      type 2 cytokines interleukin (IL)-4/13, and alternatively activated macrophages.
      Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis
      of beige fat. Mechanistically, macrophages recruited to cold-stressed
      subcutaneous white adipose tissue (scWAT) undergo alternative activation to
      induce tyrosine hydroxylase expression and catecholamine production, factors
      required for browning of scWAT. Conversely, administration of IL-4 to
      thermoneutral mice increases beige fat mass and thermogenic capacity to
      ameliorate pre-established obesity. Together, our findings have uncovered the
      efferent circuit controlling biogenesis of beige fat and provide support for its
      targeting to treat obesity. 

PMID- 24906149
TI  - Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery
      of granzymes.
AB  - When killer lymphocytes recognize infected cells, perforin delivers cytotoxic
      proteases (granzymes) into the target cell to trigger apoptosis. What happens to
      intracellular bacteria during this process is unclear. Human, but not rodent,
      cytotoxic granules also contain granulysin, an antimicrobial peptide. Here, we
      show that granulysin delivers granzymes into bacteria to kill diverse bacterial
      strains. In Escherichia coli, granzymes cleave electron transport chain complex I
      and oxidative stress defense proteins, generating reactive oxygen species (ROS)
      that rapidly kill bacteria. ROS scavengers and bacterial antioxidant protein
      overexpression inhibit bacterial death. Bacteria overexpressing a GzmB
      uncleavable mutant of the complex I subunit nuoF or strains that lack complex I
      still die, but more slowly, suggesting that granzymes disrupt multiple vital
      bacterial pathways. Mice expressing transgenic granulysin are better able to
      clear Listeria monocytogenes. Thus killer cells play an unexpected role in
      bacterial defense. 

PMID- 24906150
TI  - Hippo pathway activity influences liver cell fate.
AB  - The Hippo-signaling pathway is an important regulator of cellular proliferation
      and organ size. However, little is known about the role of this cascade in the
      control of cell fate. Employing a combination of lineage tracing, clonal
      analysis, and organoid culture approaches, we demonstrate that Hippo pathway
      activity is essential for the maintenance of the differentiated hepatocyte state.
      Remarkably, acute inactivation of Hippo pathway signaling in vivo is sufficient
      to dedifferentiate, at very high efficiencies, adult hepatocytes into cells
      bearing progenitor characteristics. These hepatocyte-derived progenitor cells
      demonstrate self-renewal and engraftment capacity at the single-cell level. We
      also identify the NOTCH-signaling pathway as a functional important effector
      downstream of the Hippo transducer YAP. Our findings uncover a potent role for
      Hippo/YAP signaling in controlling liver cell fate and reveal an unprecedented
      level of phenotypic plasticity in mature hepatocytes, which has implications for
      the understanding and manipulation of liver regeneration.

PMID- 24906151
TI  - Increased adipocyte O2 consumption triggers HIF-1alpha, causing inflammation and
      insulin resistance in obesity.
AB  - Adipose tissue hypoxia and inflammation have been causally implicated in obesity
      induced insulin resistance. Here, we report that, early in the course of high-fat
      diet (HFD) feeding and obesity, adipocyte respiration becomes uncoupled, leading
      to increased oxygen consumption and a state of relative adipocyte hypoxia. These
      events are sufficient to trigger HIF-1alpha induction, setting off the chronic
      adipose tissue inflammatory response characteristic of obesity. At the molecular
      level, these events involve saturated fatty acid stimulation of the adenine
      nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, which
      leads to the uncoupled respiratory state. Genetic or pharmacologic inhibition of
      either ANT2 or HIF-1alpha can prevent or reverse these pathophysiologic events,
      restoring a state of insulin sensitivity and glucose tolerance. These results
      reveal the sequential series of events in obesity-induced inflammation and
      insulin resistance. 

PMID- 24906153
TI  - The rhino-deadlock-cutoff complex licenses noncanonical transcription of dual
      strand piRNA clusters in Drosophila.
AB  - Argonaute proteins of the PIWI clade are central to transposon silencing in
      animal gonads. Their target specificity is defined by 23-30 nt PIWI interacting
      RNAs (piRNAs), which mostly originate from discrete genomic loci termed piRNA
      clusters. Here, we show that a complex composed of Rhino, Deadlock, and Cutoff
      (RDC) defines dual-strand piRNA clusters genome-wide in Drosophila ovaries. The
      RDC is anchored to H3K9me3-marked chromatin in part via Rhino's chromodomain.
      Depletion of Piwi results in loss of the RDC and small RNAs at a subset of piRNA
      clusters, demonstrating a feedback loop between Piwi and piRNA source loci.
      Intriguingly, profiles of RNA polymerase II occupancy, nascent transcription, and
      steady-state RNA levels reveal that the RDC licenses noncanonical transcription
      of dual-strand piRNA clusters. Likely, this process involves 5' end protection of
      nascent RNAs and suppression of transcription termination. Our data provide key
      insight into the regulation and evolution of piRNA clusters.

PMID- 24906152
TI  - The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor
      splicing.
AB  - piRNAs guide an adaptive genome defense system that silences transposons during
      germline development. The Drosophila HP1 homolog Rhino is required for germline
      piRNA production. We show that Rhino binds specifically to the heterochromatic
      clusters that produce piRNA precursors, and that binding directly correlates with
      piRNA production. Rhino colocalizes to germline nuclear foci with Rai1/DXO
      related protein Cuff and the DEAD box protein UAP56, which are also required for
      germline piRNA production. RNA sequencing indicates that most cluster transcripts
      are not spliced and that rhino, cuff, and uap56 mutations increase expression of
      spliced cluster transcripts over 100-fold. LacI::Rhino fusion protein binding
      suppresses splicing of a reporter transgene and is sufficient to trigger piRNA
      production from a trans combination of sense and antisense reporters. We
      therefore propose that Rhino anchors a nuclear complex that suppresses cluster
      transcript splicing and speculate that stalled splicing differentiates piRNA
      precursors from mRNAs. 

PMID- 24906154
TI  - Bromine is an essential trace element for assembly of collagen IV scaffolds in
      tissue development and architecture.
AB  - Bromine is ubiquitously present in animals as ionic bromide (Br(-)) yet has no
      known essential function. Herein, we demonstrate that Br(-) is a required
      cofactor for peroxidasin-catalyzed formation of sulfilimine crosslinks, a
      posttranslational modification essential for tissue development and architecture
      found within the collagen IV scaffold of basement membranes (BMs). Bromide,
      converted to hypobromous acid, forms a bromosulfonium-ion intermediate that
      energetically selects for sulfilimine formation. Dietary Br deficiency is lethal
      in Drosophila, whereas Br replenishment restores viability, demonstrating its
      physiologic requirement. Importantly, Br-deficient flies phenocopy the
      developmental and BM defects observed in peroxidasin mutants and indicate a
      functional connection between Br(-), collagen IV, and peroxidasin. We establish
      that Br(-) is required for sulfilimine formation within collagen IV, an event
      critical for BM assembly and tissue development. Thus, bromine is an essential
      trace element for all animals, and its deficiency may be relevant to BM
      alterations observed in nutritional and smoking-related disease. PAPERFLICK: 

PMID- 24906155
TI  - Molecular basis for age-dependent microtubule acetylation by tubulin
      acetyltransferase.
AB  - Acetylation of alpha-tubulin Lys40 by tubulin acetyltransferase (TAT) is the only
      known posttranslational modification in the microtubule lumen. It marks stable
      microtubules and is required for polarity establishment and directional
      migration. Here, we elucidate the mechanistic underpinnings for TAT activity and
      its preference for microtubules with slow turnover. 1.35 A TAT cocrystal
      structures with bisubstrate analogs constrain TAT action to the microtubule lumen
      and reveal Lys40 engaged in a suboptimal active site. Assays with diverse tubulin
      polymers show that TAT is stimulated by microtubule interprotofilament contacts.
      Unexpectedly, despite the confined intraluminal location of Lys40, TAT
      efficiently scans the microtubule bidirectionally and acetylates stochastically
      without preference for ends. First-principles modeling and single-molecule
      measurements demonstrate that TAT catalytic activity, not constrained luminal
      diffusion, is rate limiting for acetylation. Thus, because of its preference for
      microtubules over free tubulin and its modest catalytic rate, TAT can function as
      a slow clock for microtubule lifetimes. 

PMID- 24906156
TI  - A "push and slide" mechanism allows sequence-insensitive translocation of
      secretory proteins by the SecA ATPase.
AB  - In bacteria, most secretory proteins are translocated across the plasma membrane
      by the interplay of the SecA ATPase and the SecY channel. How SecA moves a broad
      range of polypeptide substrates is only poorly understood. Here we show that SecA
      moves polypeptides through the SecY channel by a "push and slide" mechanism. In
      its ATP-bound state, SecA interacts through a two-helix finger with a subset of
      amino acids in a substrate, pushing them into the channel. A polypeptide can also
      passively slide back and forth when SecA is in the predominant ADP-bound state or
      when SecA encounters a poorly interacting amino acid in its ATP-bound state. SecA
      performs multiple rounds of ATP hydrolysis before dissociating from SecY. The
      proposed push and slide mechanism is supported by a mathematical model and
      explains how SecA allows translocation of a wide range of polypeptides. This
      mechanism may also apply to hexameric polypeptide-translocating ATPases. 

PMID- 24906158
TI  - A hierarchical map of regulatory genetic interactions in membrane trafficking.
AB  - Endocytosis is critical for cellular physiology and thus is highly regulated. To
      identify regulatory interactions controlling the endocytic membrane system, we
      conducted 13 RNAi screens on multiple endocytic activities and their downstream
      organelles. Combined with image analysis of thousands of single cells per
      perturbation and their cell-to-cell variability, this created a high-quality and
      cross-comparable quantitative data set. Unbiased analysis revealed emergent
      properties of the endocytic membrane system and how its complexity evolved and
      distinct programs of regulatory control that coregulate specific subsets of
      endocytic uptake routes and organelle abundances. We show that these subset
      effects allow the mapping of functional regulatory interactions and their
      interaction motifs between kinases, membrane-trafficking machinery, and the
      cytoskeleton at a large scale, some of which we further characterize. Our work
      presents a powerful approach to identify regulatory interactions in complex
      cellular systems from parallel single-gene or double-gene perturbation screens in
      human cells and yeast. 

PMID- 24906159
TI  - SnapShot: resident memory T cells.
AB  - Resident memory T cells (TRM) comprise a subset of nonrecirculating memory T
      cells that remain positioned at common portals of reinfection. These include
      barrier tissues such as the mucosae and skin. TRM orchestrate the initial
      response to pathogens re-encountered at these locales, thereby accelerating
      protective immune responses. 

PMID- 24906160
TI  - Solvation and spectral line shifts of chromium atoms in helium droplets based on
      a density functional theory approach.
AB  - The interaction of an electronically excited, single chromium (Cr) atom with
      superfluid helium nanodroplets of various size (10 to 2000 helium (He) atoms) is
      studied with helium density functional theory. Solvation energies and pseudo
      diatomic potential energy surfaces are determined for Cr in its ground state as
      well as in the y(7)P, a(5)S, and y(5)P excited states. The necessary Cr-He pair
      potentials are calculated by standard methods of molecular orbital-based
      electronic structure theory. In its electronic ground state the Cr atom is found
      to be fully submerged in the droplet. A solvation shell structure is derived from
      fluctuations in the radial helium density. Electronic excitations of an embedded
      Cr atom are simulated by confronting the relaxed helium density (rhoHe), obtained
      for Cr in the ground state, with interaction pair potentials of excited states.
      The resulting energy shifts for the transitions z(7)P <- a(7)S, y(7)P <- a(7)S,
      z(5)P <- a(5)S, and y(5)P <- a(5)S are compared to recent fluorescence and
      photoionization experiments. 

PMID- 24906157
TI  - Quantitative temporal viromics: an approach to investigate host-pathogen
      interaction.
AB  - A systematic quantitative analysis of temporal changes in host and viral proteins
      throughout the course of a productive infection could provide dynamic insights
      into virus-host interaction. We developed a proteomic technique called
      "quantitative temporal viromics" (QTV), which employs multiplexed tandem-mass-tag
      based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important
      pathogen but a paradigm of viral immune evasion. QTV detailed how HCMV
      orchestrates the expression of >8,000 cellular proteins, including 1,200 cell
      surface proteins to manipulate signaling pathways and counterintrinsic, innate,
      and adaptive immune defenses. QTV predicted natural killer and T cell ligands, as
      well as 29 viral proteins present at the cell surface, potential therapeutic
      targets. Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical
      HCMV open reading frames were defined. QTV is a powerful method that can yield
      important insights into viral infection and is applicable to any virus with a
      robust in vitro model.

PMID- 24906162
TI  - Carbon isotope compositions (delta(13) C) of leaf, wood and holocellulose differ
      among genotypes of poplar and between previous land uses in a short-rotation
      biomass plantation.
AB  - The efficiency of water use to produce biomass is a key trait in designing
      sustainable bioenergy-devoted systems. We characterized variations in the carbon
      isotope composition (delta(13) C) of leaves, current year wood and holocellulose
      (as proxies for water use efficiency, WUE) among six poplar genotypes in a short
      rotation plantation. Values of delta(13) Cwood and delta(13) Cholocellulose were
      tightly and positively correlated, but the offset varied significantly among
      genotypes (0.79-1.010/00). Leaf phenology was strongly correlated with delta(13)
      C, and genotypes with a longer growing season showed a higher WUE. In contrast,
      traits related to growth and carbon uptake were poorly linked to delta(13) C.
      Trees growing on former pasture with higher N-availability displayed higher
      delta(13) C as compared with trees growing on former cropland. The positive
      relationships between delta(13) Cleaf and leaf N suggested that spatial
      variations in WUE over the plantation were mainly driven by an N-related effect
      on photosynthetic capacities. The very coherent genotype ranking obtained with
      delta(13) C in the different tree compartments has some practical outreach.
      Because WUE remains largely uncoupled from growth in poplar plantations, there is
      potential to identify genotypes with satisfactory growth and higher WUE. 

PMID- 24906163
TI  - Dehalogenation and coupling of a polycyclic hydrocarbon on an atomically thin
      insulator.
AB  - Catalytic activity is of pivotal relevance in enabling efficient and selective
      synthesis processes. Recently, covalent coupling reactions catalyzed by solid
      metal surfaces opened the rapidly evolving field of on-surface chemical
      synthesis. Tailored molecular precursors in conjunction with the catalytic
      activity of the metal substrate allow the synthesis of novel, technologically
      highly relevant materials such as atomically precise graphene nanoribbons.
      However, the reaction path on the metal substrate remains unclear in most cases,
      and the intriguing question is how a specific atomic configuration between
      reactant and catalyst controls the reaction processes. In this study, we cover
      the metal substrate with a monolayer of hexagonal boron nitride (h-BN), reducing
      the reactivity of the metal, and gain unique access to atomistic details during
      the activation of a polyphenylene precursor by sequential dehalogenation and the
      subsequent coupling to extended oligomers. We use scanning tunneling microscopy
      and density functional theory to reveal a reaction site anisotropy, induced by
      the registry mismatch between the precursor and the nanostructured h-BN
      monolayer. 

PMID- 24906161
TI  - Fatty acids from membrane lipids become incorporated into lipid bodies during
      Myxococcus xanthus differentiation.
AB  - Myxococcus xanthus responds to amino acid limitation by producing fruiting bodies
      containing dormant spores. During development, cells produce triacylglycerides in
      lipid bodies that become consumed during spore maturation. As the cells are
      starved to induce development, the production of triglycerides represents a
      counterintuitive metabolic switch. In this paper, lipid bodies were quantified in
      wild-type strain DK1622 and 33 developmental mutants at the cellular level by
      measuring the cross sectional area of the cell stained with the lipophilic dye
      Nile red. We provide five lines of evidence that triacylglycerides are derived
      from membrane phospholipids as cells shorten in length and then differentiate
      into myxospores. First, in wild type cells, lipid bodies appear early in
      development and their size increases concurrent with an 87% decline in membrane
      surface area. Second, developmental mutants blocked at different stages of
      shortening and differentiation accumulated lipid bodies proportionate with their
      cell length with a Pearson's correlation coefficient of 0.76. Third, peripheral
      rods, developing cells that do not produce lipid bodies, fail to shorten. Fourth,
      genes for fatty acid synthesis are down-regulated while genes for fatty acid
      degradation are up regulated. Finally, direct movement of fatty acids from
      membrane lipids in growing cells to lipid bodies in developing cells was observed
      by pulse labeling cells with palmitate. Recycling of lipids released by
      Programmed Cell Death appears not to be necessary for lipid body production as a
      fadL mutant was defective in fatty acid uptake but proficient in lipid body
      production. The lipid body regulon involves many developmental genes that are not
      specifically involved in fatty acid synthesis or degradation. MazF RNA
      interferase and its target, enhancer-binding protein Nla6, appear to negatively
      regulate cell shortening and TAG accumulation whereas most cell-cell signals
      activate these processes. 

PMID- 24906164
TI  - Driver rehabilitation: a systematic review of the types and effectiveness of
      interventions used by occupational therapists to improve on-road fitness-to
      drive.
AB  - OBJECTIVE: Driver rehabilitation has the potential to improve on-road safety and
      is commonly recommended to clients. The aim of this systematic review was to
      identify what intervention approaches are used by occupational therapists as part
      of driver rehabilitation programmes, and to determine the effectiveness of these
      interventions. METHOD: Six electronic databases (MEDLINE, CINAHL, PsycInfo,
      Embase, The Cochrane Library, and OTDBase) were searched. Two authors
      independently reviewed studies reporting all types of research designs and for
      all patient populations, provided the interventions could be administered by
      occupational therapists. The methodological quality of studies was assessed using
      the 'Downs and Black Instrument', and the level of evidence for each intervention
      approach was established using 'Centre for Evidence Based Medicine' criteria.
      RESULTS: Sixteen studies were included in the review. The most common type of
      intervention approach used was computer-based driving simulator training (n=8),
      followed by off-road skill-specific training (n=4), and off-road education
      programmes (n=3). Car adaptations/modifications were used in one of the included
      studies. There was significant variability between studies with regards to
      frequency, duration, and total number of intervention sessions, and the diagnoses
      of the participants. Of the four intervention approaches, there is evidence to
      support the effectiveness of off-road skill-specific training (with older
      clients), and computer-based driving simulator training (with both older clients
      and participants with acquired brain injury). CONCLUSION: Three types of
      intervention approaches are commonly reported, however, there is limited evidence
      to determine to effectiveness of these in improving fitness-to-drive. Further
      research is required, with clients from a range of diagnostic groups to establish
      evidence-based interventions and determine their effectiveness in improving these
      clients' on-road fitness-to-drive.

PMID- 24906165
TI  - Seatbelt wearing rates in middle income countries: a cross-country analysis.
AB  - In settings with low seatbelt use prevalence, self-reported seatbelt use
      estimates often lack validity, and routine observational studies are scarce. In
      this paper, we aim to describe the prevalence of seatbelt use and associated
      factors in drivers and front-seat passengers across eight sites in four countries
      (Egypt, Mexico, Russia, Turkey) using observational studies as well as to produce
      estimates of country-level and site-level variance. As part of the Bloomberg
      Philanthropies Global Road Safety Program, data on driver and passenger seatbelt
      use across four middle-income countries was collected between October 2010 and
      May 2011 (n=122,931 vehicles). Logistic regression and Intraclass Correlation
      Coefficient analyses for sites- and country-level clustering were performed. We
      found high variability of seatbelt wearing rates ranging from 4 to 72% in drivers
      and 3-50% in front-seat passengers. Overall, average seatbelt wearing rates were
      low (under 60% in most sites). At the individual level, older and female drivers
      were more likely to wear seatbelts, as well as drivers of vehicles transiting at
      times of increased vehicle flow. We also found that 26-32% and 37-41% of the
      variance in seatbelt use among drivers and front-seat passengers respectively was
      explained by differences across sites and countries. Our results demonstrate that
      there is room for improvement on seatbelt use in middle-income countries and that
      standardized cross-country studies on road safety risk factors are feasible,
      providing valuable information for prevention and monitoring activities. 

PMID- 24906166
TI  - Patient with liver dysfunction while maintained on veno-venous extracorporeal
      membrane oxygenation should not be overlooked as a potential donor.
AB  - This report describes transplantation of liver allograft from a circulatory death
      donor who was supported by veno-venous extracorporeal membrane oxygenation (ECMO)
      for 14 days and presented with severely altered liver functions. Successful liver
      transplant was done in a patient with hepatocellular carcinoma (HCC) in the
      background of primary sclerosing cholangitis. There was immediate graft function
      and uneventful recovery with stable graft function at 1-year follow-up. This case
      illustrates the ability of veno-venous ECMO to resuscitate organs in the presence
      of severe dysfunction, and perhaps, lessons from this case may be incorporated to
      optimize the condition of organs rescued from these marginal donors and exemplify
      the use of ECMO in normothermic regional perfusion in donors after circulatory
      death.

PMID- 24906167
TI  - Editorial comment.

PMID- 24906170
TI  - Fast direct synthesis and compaction of homogenous phase-pure thermoelectric
      Zn4Sb3.
AB  - Zn4Sb3 is among the cheapest high performance thermoelectric materials, and it is
      made of relatively nontoxic elements. Strong activities are aimed at developing
      commercial power generation modules based on Zn4Sb3 making it vital to develop
      fast reliable synthesis processes for high-quality material. Here direct
      synthesis and compaction of homogeneous phase-pure thermoelectric Zn4Sb3 by spark
      plasma sintering (SPS) has been developed. Compared with the traditional quench
      and press method, the complexity and process time of the new method is very
      significantly reduced (order of magnitude), making large-scale production
      feasible. A composition gradient is observed in the pellet along the axis of
      applied pressure and current. The homogeneity of the pressed pellets is studied
      as a function of the SPS parameters: sintering time, applied current, sintering
      temperature and applied pressure, and the mechanism behind the formation of the
      gradient is discussed. The key finding is that pure and homogeneous Zn4Sb3
      pellets can be produced by adding an extra layer of elemental Zn foil to
      compensate the Zn migration. 

PMID- 24906171
TI  - Lipodiscamides A-C, new cytotoxic lipopeptides from Discodermia kiiensis.
AB  - Lipodiscamides A-C, three new lipodepsipeptides, were characterized from the
      marine sponge Discodermia kiiensis. These structurally rare cyclic
      lipodepsipeptides were found to possess an unprecedented dilactone macrocycle
      and, thus, represent a new family of lipopeptides. They are the only lipopeptides
      bearing 4S-hydroxy-trans-2-enoate, and noncanonical amino acids, l-3
      ureidoalanine (Uda), E-dehydronorvaline (Denor), and d-citrulline (Cit). MTT
      assays against P388 and HeLa cells revealed the moderate cytotoxicity of all
      three compounds. 

PMID- 24906172
TI  - Central pulse pressure links microalbuminuria with plasma B-type natriuretic
      peptide elevation: causal implication for cardiorenal syndrome in hypertension.
AB  - OBJECTIVE: A pathological connection between the heart and kidney is well
      recognized as a cardiorenal syndrome, but the underlying mechanism remains
      undetermined. We hypothesized that this connection is attributable to central
      haemodynamic alterations. METHODS: In 386 patients with hypertension, the radial,
      carotid and femoral pressure waveforms were recorded with applanation tonometry
      to estimate the aortic pressure and pulse wave velocity (PWV). The plasma B-type
      natriuretic peptide (BNP) concentration and urinary albumin/creatinine ratio
      (UACR), cardiac and renal damage biomarkers, respectively, were also measured for
      each patient. RESULTS: The BNP was correlated positively with UACR, aortic pulse
      pressure and PWV, but inversely with the estimated glomerular filtration rate
      (eGFR, P < 0.001). The aortic pulse pressure tended to more closely correlate
      with BNP than the brachial pulse pressure. The presence of (micro)albuminuria
      (UACR >=30 mg/g) was associated with BNP elevation (>=50 pg/ml) independently of
      age, BMI, mean arterial pressure, eGFR and beta-blocker treatment (odds ratio:
      2.41; P = 0.04). However, further adjustment for the aortic pulse pressure or PWV
      rendered this albuminuria-BNP relationship insignificant (P = 0.25) and, instead,
      the aortic pulse pressure emerged as the strongest determinant of BNP elevation
      (odds ratio: 1.51 per 10mmHg; P = 0.001). Differently from albuminuria, lower
      eGFR was consistently related to higher plasma BNP, even after controlling for
      the aortic pressure and PWV. CONCLUSION: Concomitant plasma BNP elevation with
      (micro)albuminuria can be explained by increases in aortic pulse pressure and
      PWV. This finding suggests that the altered central haemodynamics causes
      simultaneous damage/dysfunction in the heart and kidney, which could then
      contribute to cardiorenal syndrome in hypertension.

PMID- 24906173
TI  - Symptoms of anxiety and depression across adulthood and blood pressure in late
      middle age: the 1946 British birth cohort.
AB  - OBJECTIVE: Previous studies testing the hypothesis that symptoms of anxiety and
      depression increase blood pressure (BP) levels show inconsistent and limited
      findings. We examined the association between those symptoms across adult life
      and BP in late middle age. METHODS: Using data from 1683 participants from the
      MRC NSHD, we investigated associations between affective symptoms at ages 36, 43,
      53 and 60-64 years and SBP and DBP at age 60-64. Multivariable linear regression
      was used to examine the effect on BP of affective symptoms at each age separately
      and as a categorical cumulative score based on the number of times an individual
      was classified as a 'case'. Models were adjusted for sex, BMI, educational
      attainment, socio-economic position, heart rate, lifestyle factors and
      antihypertensive treatment. RESULTS: In fully adjusted models, we observed lower
      SBP in study members with case-level symptoms at one to two time-points [-1.83
      mmHg; 95% confidence interval (CI) -3.74 to 0.01] and at three to four time
      points (-3.93 mmHg; 95% CI -7.19 to -0.68) compared with those never meeting case
      criteria suggesting a cumulative inverse impact of affective symptoms on SBP
      across adulthood (P value for trend 0.022). Sex and BMI had a large impact on the
      estimates while not other confounders. Potential mediators such as heart rate and
      lifestyle behaviours had a little impact on the association. SBP at age 36 and
      behavioural changes across adulthood, as additional covariates, had a little
      impact on the association. A similar but weaker trend was observed for DBP.
      CONCLUSION: A cumulative effect of symptoms of anxiety and depression across
      adulthood results in lower SBP in late middle age that is not explained by
      lifestyle factors and antihypertensive treatment. Mechanisms by which mood may
      impact BP should be investigated.

PMID- 24906174
TI  - Effects on office and home blood pressure of the lercanidipine-enalapril
      combination in patients with Stage 2 hypertension: a European randomized,
      controlled clinical trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of
      combinations of lercanidipine (L) and enalapril (E) at different doses on office
      and home blood pressure (BP) in patients with Stage 2 hypertension. STUDY DESIGN:
      This was a randomized, double-blind, placebo-controlled, factorial study
      conducted in 100 centres from seven countries. Patients with office DBP 100-109
      mmHg and home DBP at least 85 mmHg at the end of a 2-week placebo run-in period
      were randomized to a 10-week treatment with placebo, L (10 or 20 mg), E (10 or 20
      mg) or the four L-E combinations. The efficacy parameters were office DBP at
      trough (primary), SBP at trough and home SBP and DBP. Office BP was measured at
      each visit in both the sitting and the standing position, while home BP was
      measured twice in the morning and twice in the evening for at least 3 days before
      treatment and at study end. Safety parameters included adverse events, laboratory
      tests and 12-lead ECG. RESULTS: A total of 1039 patients were randomized (48%
      men, mean age 54 years, mean BMI 30 kg/m, 40% obese patients). Baseline BP was
      similar in all groups and lower for home than for office values (149/95 and
      159/103 mmHg, respectively). A marked placebo effect was observed on office but
      not on home BP. Combination therapy was superior to placebo at all doses for both
      office and home BP. The greatest effect was observed in the L20/E20 group, in
      which the SBP/DBP fall amounted to -19.2/-15.2 and -13.2/-7.5 mmHg for sitting
      office and home BP, respectively. Similar reductions were observed on standing
      office BP. The L20/E20 combination was associated with less cough, palpitations
      and leg oedema than monotherapies, with no increased rate of dizziness or
      hypotension. CONCLUSION: In Stage 2 hypertension, a fixed-dose combination of L
      and E ensures a control of both office and out-of-office BP, with a favourable
      tolerability profile.

PMID- 24906176
TI  - Fish genomes provide novel insights into the evolution of vertebrate secretin
      receptors and their ligand.
AB  - The secretin receptor (SCTR) is a member of Class 2 subfamily B1 GPCRs and part
      of the PAC1/VPAC receptor subfamily. This receptor has long been known in mammals
      but has only recently been identified in other vertebrates including teleosts,
      from which it was previously considered to be absent. The ligand for SCTR in
      mammals is secretin (SCT), an important gastrointestinal peptide, which in
      teleosts has not yet been isolated, or the gene identified. This study revises
      the evolutionary model previously proposed for the secretin-GPCRs in metazoan by
      analysing in detail the fishes, the most successful of the extant vertebrates.
      All the Actinopterygii genomes analysed and the Chondrichthyes and Sarcopterygii
      fish possess a SCTR gene that shares conserved sequence, structure and synteny
      with the tetrapod homologue. Phylogenetic clustering and gene environment
      comparisons revealed that fish and tetrapod SCTR shared a common origin and
      diverged early from the PAC1/VPAC subfamily group. In teleosts SCTR duplicated as
      a result of the fish specific whole genome duplication but in all the teleost
      genomes analysed, with the exception of tilapia (Oreochromis niloticus), one of
      the duplicates was lost. The function of SCTR in teleosts is unknown but
      quantitative PCR revealed that in both sea bass (Dicentrarchus labrax) and
      tilapia (Oreochromis mossambicus) transcript abundance is high in the
      gastrointestinal tract suggesting it may intervene in similar processes to those
      in mammals. In contrast, no gene encoding the ligand SCT was identified in the
      ray-finned fishes (Actinopterygii) although it was present in the coelacanth
      (lobe finned fish, Sarcopterygii) and in the elephant shark (holocephalian). The
      genes in linkage with SCT in tetrapods and coelacanth were also identified in ray
      finned fishes supporting the idea that it was lost from their genome. At present
      SCTR remains an orphan receptor in ray-finned fishes and it will be of interest
      in the future to establish why SCT was lost and which ligand substitutes for it
      so that full characterization of the receptor can occur. 

PMID- 24906175
TI  - Fast Bayesian parameter estimation for stochastic logistic growth models.
AB  - The transition density of a stochastic, logistic population growth model with
      multiplicative intrinsic noise is analytically intractable. Inferring model
      parameter values by fitting such stochastic differential equation (SDE) models to
      data therefore requires relatively slow numerical simulation. Where such
      simulation is prohibitively slow, an alternative is to use model approximations
      which do have an analytically tractable transition density, enabling fast
      inference. We introduce two such approximations, with either multiplicative or
      additive intrinsic noise, each derived from the linear noise approximation (LNA)
      of a logistic growth SDE. After Bayesian inference we find that our fast LNA
      models, using Kalman filter recursion for computation of marginal likelihoods,
      give similar posterior distributions to slow, arbitrarily exact models. We also
      demonstrate that simulations from our LNA models better describe the
      characteristics of the stochastic logistic growth models than a related approach.
      Finally, we demonstrate that our LNA model with additive intrinsic noise and
      measurement error best describes an example set of longitudinal observations of
      microbial population size taken from a typical, genome-wide screening experiment.

PMID- 24906177
TI  - Analysis on the go: quantitation of drugs of abuse in dried urine with digital
      microfluidics and miniature mass spectrometry.
AB  - We report the development of a method coupling microfluidics and a miniature mass
      spectrometer, applied to quantitation of drugs of abuse in urine. A custom
      digital microfluidic system was designed to deliver droplets of solvent to dried
      urine samples and then transport extracted analytes to an array of
      nanoelectrospray emitters for analysis. Tandem mass spectrometry (MS/MS)
      detection was performed using a fully autonomous 25 kg instrument. Using the new
      method, cocaine, benzoylecgonine, and codeine can be quantified from four samples
      in less than 15 min from (dried) sample to analysis. The figures of merit for the
      new method suggest that it is suitable for on-site screening; for example, the
      limit of quantitation (LOQ) for cocaine is 40 ng/mL, which is compatible with the
      performance criteria for laboratory analyses established by the United Nations
      Office on Drugs and Crime. More importantly, the LOQ of the new method is
      superior to the 300 ng/mL cutoff values used by the only other portable analysis
      systems we are aware of (relying on immunoassays). This work serves as a proof-of
      concept for integration of microfluidics with miniature mass spectrometry. The
      system is attractive for the quantitation of drugs of abuse from urine and, more
      generally, may be useful for a wide range of applications that would benefit from
      portable, quantitative, on-site analysis. 

PMID- 24906178
TI  - Comparative genomics of the protocatechuate branch of the beta-ketoadipate
      pathway in the Roseobacter lineage.
AB  - The protocatechuate branch of the beta-ketoadipate pathway is the most common
      pathway for degradation of monoaromatic compounds in the Roseobacter lineage. We
      analyzed 43 Roseobacter genomes in order to determine if they possessed all
      genetic elements for this pathway and if there were common patterns in gene
      organization. The eight genes of the pathway (pcaG, -H, -B, -C, -D, -I, -J, and 
      F), possible regulators, and genes encoding for proteins with related function
      (i.e. catabolism of 4-hydroxybenzoate, catechol, and meta-cleavage of
      protocatechuate) were predicted by sequence homology analysis. Most of the
      Roseobacters studied had putatively a complete protocatechuate branch of the beta
      ketoadipate pathway while 11 of them would probably have an incomplete pathway.
      Thirty-one Roseobacters would be potentially able of transforming 4
      hydroxybenzoate to protocatechuate, and 13 of them might transform catechol via
      ortho-cleavage, the starting reaction of the catechol branch of the beta
      ketoadipate pathway. We observed variability in gene organization, with no clear
      relationship between gene order and Roseobacter taxonomy. Genes were usually
      organized in several gene clusters. One of the clusters (pcaRIJF) was not
      reported previously in Roseobacters. The presence of the putative regulator pcaR
      in these bacteria was also a novel finding. The conserved ORF (chp), encoding for
      a protein of family DUF849 whose functional role has been proven recently, was
      detected in 34 genomes. Sequence homology confirmed that proteins encoded by chp
      corresponded to putative BKACE G4 proteins, which are able to transform beta
      ketoadipate. Therefore, most Roseobacters seemed to possess two different enzymes
      for transforming beta-ketoadipate. We also report two possible regulation
      mechanisms of gene pobA (encoding for the enzyme transforming 4-hydroxybenzoate
      to protocatechuate): via PcaQ, the regulator commonly found with pca genes, and
      via an independent regulator (PobR). The results of this study evidence the
      relevance of 4-hydroxybenzoate, protocatechuate and beta-ketoadipate degradation
      pathways in Roseobacters and provide a more complex view of possible regulation
      mechanisms. 

PMID- 24906179
TI  - Palladium-nanoparticle-catalyzed 1,7-palladium migration involving C-H
      activation, followed by intramolecular amination: regioselective synthesis of N1
      arylbenzotriazoles and an evaluation of their inhibitory activity toward
      indoleamine 2,3-dioxygenase.
AB  - A sulfur-modified gold-supported palladium material (SAPd) has been developed
      bearing palladium nanoparticles on its surface. Herein, we report for the first
      time the use of SAPd to affect a Pd-nanoparticle-catalyzed 1,7-Pd migration
      reaction for the synthesis of benzotriazoles via C-H bond activation. The
      resulting benzotriazoles were evaluated in terms of their inhibitory activity
      toward indoleamine 2,3-dioxygenase. 

PMID- 24906180
TI  - Designing nitrogen-enriched echinus-like carbon capsules for highly efficient
      oxygen reduction reaction and lithium ion storage.
AB  - Both structural and compositional modulations are important for high-performance
      electrode materials in energy conversion/storage devices. Here hierarchical
      structure nitrogen-rich hybrid porous carbon capsules with bamboo-like carbon
      nanotube whiskers (N-CC@CNTs) grown in situ have been specifically designed,
      which combine the advantageous features of high surface area, abundant active
      sites, easy access to medium and favorable mass transport. As a result, the newly
      prepared N-CC@CNTs show highly efficient catalytic activity in oxygen reduction
      reaction in alkaline media for fuel cells, which not only outperforms commercial
      Pt-based catalysts in terms of kinetic limiting current, stability and tolerance
      to methanol crossover effect, but is also better than most of the nanostructured
      carbon-based catalysts reported previously. On the other hand, as an anode
      material for lithium ion batteries, the N-CC@CNTs obtained also exhibit an
      excellent reversible capacity of ca. 1337 mA h g(-1) at 0.5 A g(-1), outstanding
      rate capability and long cycling stability, even at a current density of 20 A g(
      1). The capacity is the highest among all the heteroatom-doped carbon materials
      reported so far, and is even higher than that of many of the composites of metal,
      metal oxides or metal sulfides with carbon materials. 

PMID- 24906181
TI  - Development of a universal anti-adalimumab antibody standard for interlaboratory
      harmonization.
AB  - BACKGROUND: Therapeutic drug monitoring of adalimumab (ADM) has been introduced
      recently. When no detectable ADM serum concentrations can be found, the formation
      of antidrug antibodies (ADA) should be investigated. A variety of assays to
      measure the occurrence of ADA have been developed. Results are expressed as
      arbitrary units or as a titration value. The aim was to develop a monoclonal
      antibody (MA) that could serve as a universal calibrator to quantify the amount
      of ADA in ADM-treated patients. METHODS: Hybridoma technology was used to
      generate a MA toward ADM. The functionality of the MA was tested in a bridging
      enzyme linked immunosorbent assay (ELISA) setup and in a cell-based assay. Sera
      from 25 anti-tumor necrosis factor naive patients with inflammatory bowel disease
      were used to determine the cutoff values. Sera from 9 ADM-treated patients with
      inflammatory bowel disease, with undetectable serum concentrations of ADM were
      used to quantify the ADA response. RESULTS: In this study, MA-ADM6A10, an IgG1
      that can be used as a calibrator in both an ELISA to quantify the amount of
      binding antibodies and in a cell-based assay to quantify the amount of
      neutralizing antibodies, was generated. Combining the results of both assays
      showed that the sera with high concentrations of anti-ADM binding antibodies also
      had the highest neutralizing capacity. CONCLUSIONS: The availability of a
      universal calibrator could facilitate the interlaboratory harmonization of
      antibody titers in patients who develop anti-adalimumab antibodies.

PMID- 24906183
TI  - Sexual and reproductive health care issues in nurse practitioner preparation: the
      dialogue continues.

PMID- 24906182
TI  - Mg2+ homeostasis: the balancing act of TRPM6.
AB  - PURPOSE OF REVIEW: The tight control of blood magnesium (Mg) levels is of central
      importance for numerous physiological processes. A persistent low Mg status
      (hypomagnesemia) is associated with severe health risks and is involved in the
      pathogenesis of type 2 diabetes mellitus, osteoporosis, asthma, and heart and
      vascular diseases. The current view has expanded significantly as a result of the
      identification of novel genes and regulatory pathways involved in hypomagnesemic
      disorders. This review aims to give an up-to-date overview of transient receptor
      potential melastatin 6 (TRPM6) regulation and its role in the maintenance of Mg
      homeostasis. RECENT FINDINGS: The epithelial Mg channel TRPM6 is considered to be
      the Mg entry pathway in the distal convoluted tubule of the kidney, where it
      functions as gatekeeper for controlling the body's Mg balance. Various factors
      and hormones contribute not only to the function, but also to the dysregulation
      of TRPM6, which has a substantial impact on renal Mg handling. Recent genetic and
      molecular studies have further elucidated the signaling processes of epithelial
      Mg transport, including their effect on the expression and function of TRPM6.
      SUMMARY: Knowledge of TRPM6 functioning is of vital importance to decipher its
      role in Mg handling and will, in particular, provide a molecular basis for
      achieving a better understanding of Mg mal(re)absorption and hence systemic Mg
      balance.

PMID- 24906184
TI  - A response from the Women's Health Expert Panel (WHEP) of the American Academy of
      Nursing (AAN).

PMID- 24906185
TI  - Effects of the applications of oil drip onto surface and of the use of a
      temperature of 35 degrees C for 4 days on some physicochemical, microbiological
      and sensory characteristics of dry-cured ham.
AB  - The effects of: a) applications of oil drip (from aged salted pork fat) onto dry
      cured ham surface and b) application of a temperature of 35 degrees C for 4days
      after 234days of processing (HTST treatment) were evaluated. The oil application
      reduced moisture, proteolysis and white film in semimembranosus, microbial counts
      in adductor and the intensity of hollow extent, toasted flavour, adhesiveness,
      pastiness (in semimembranosus) and chewiness (in semimembranosus and biceps
      femoris) and increased the intensity of nutty flavour (in both muscles), aged
      flavour, hardness, fibrousness and overall liking (in semimembranosus). The HTST
      did not affect any ham characteristics. 

PMID- 24906186
TI  - Effect of enhancement on the formation of heterocyclic amines in cooked pork
      loins: preliminary studies.
AB  - Heterocyclic amines (HCAs) which are produced in meats cooked at high temperature
      a risk factor for certain human cancers. This study evaluated the effect of
      enhancement on HCA formation in cooked pork loins. Three samples of pork loin
      were prepared including non-injected loin, 12% water-injected loin, and 12%
      salt/phosphate injected loin. The HCAs were identified in all samples: PhIP (2
      amino-1-methyl-6-phenylimidazo [4,5-b]pyridine), MeIQx (2-amino-3,8
      dimethylimidazo [4,5-f]quinoxaline), and DiMeIQx (2-amino-3,4,8-trimethylimidazo
      [4,5-f]quinoxaline). Injection of salt/phosphate significantly reduced the level
      of PhIP by 42.7%, MeIQx by 79.0%, and DiMeIQx by 75.0%. Enhancement with water
      alone did not reduce HCA formation. 

PMID- 24906187
TI  - Identification of DNA methylation changes in newborns related to maternal smoking
      during pregnancy.
AB  - BACKGROUND: Maternal smoking during pregnancy is associated with significant
      infant morbidity and mortality, and may influence later disease risk. One
      mechanism by which smoking (and other environmental factors) might have long
      lasting effects is through epigenetic modifications such as DNA methylation.
      OBJECTIVES: We conducted an epigenome-wide association study (EWAS) investigating
      alterations in DNA methylation in infants exposed in utero to maternal tobacco
      smoke, using the Norway Facial Clefts Study. METHODS: The Illumina
      HumanMethylation450 BeadChip was used to assess DNA methylation in whole blood
      from 889 infants shortly after delivery. Of 889 mothers, 287 reported smoking
      twice as many smokers as in any previous EWAS of maternal smoking. CpG sites
      related to maternal smoking during the first trimester were identified using
      robust linear regression. RESULTS: We identified 185 CpGs with altered
      methylation in infants of smokers at genome-wide significance (q-value < 0.05;
      mean Deltabeta = +/- 2%). These correspond to 110 gene regions, of which 7 have
      been previously reported and 10 are newly confirmed using publicly available
      results. Among these 10, the most noteworthy are FRMD4A, ATP9A, GALNT2, and MEG3,
      implicated in processes related to nicotine dependence, smoking cessation, and
      placental and embryonic development. CONCLUSIONS: Our study identified 10 genes
      with newly established links to maternal smoking. Further, we note differences
      between smoking-related methylation changes in newborns and adults, suggesting
      possible distinct effects of direct versus indirect tobacco smoke exposure as
      well as potential differences due to age. Further work would be needed to
      determine whether these small changes in DNA methylation are biologically or
      clinically relevant. The methylation changes identified in newborns may mediate
      the association between in utero maternal smoking exposure and later health
      outcomes.

PMID- 24906188
TI  - Nephroureterectomy surgery in the UK in 2012: British Association of Urological
      Surgeons (BAUS) Registry data.
AB  - OBJECTIVE: To report registry data obtained by the British Association of
      Urological Surgeons (BAUS) for nephroureterectomy (NU) surgery in the UK
      performed between 1 January and 31 December 2012. SUBJECTS/PATIENTS AND METHODS:
      Registry data entered by each individual surgeon's team (self-reported) on all
      6042 nephrectomy surgeries reported to BAUS during 2012 were analysed to identify
      all NU surgery. Parameters for analysis included demographics, indication, type
      of surgery, histopathology and complications (Clavien system) of surgery. Data
      did not include tumour location or multiplicity, preoperative diagnostic
      evaluation or details of minimally invasive surgery (MIS) undertaken. Before
      analysis for this report a central process of 'data-cleansing' was undertaken by
      a BAUS group to address any discrepancy between the listed surgery and the
      preoperative indication. RESULTS: In all, 863 NU surgeries were included,
      performed by 220 consultant surgeons in 119 centres, and the median (range)
      number of NU per surgeon and unit was 3 (1-20) and 6 (1-29), respectively. The
      most common age group was 71-80 years (40%), most were male (64%), and haematuria
      was the most common presentation (74%). The dominant pathology was upper tract
      urothelial cancer (89%, 735), with final stage >=pT2 in 47% (367), and the grade
      was 1, 2 or 3 in 6% (38), 36% (228) and 58% (362) respectively. Operative
      technique included MIS in 85% (720) and total reported operative complication
      rate (any Clavien) was 15% (128), of which Clavien >=3 was reported in 4% (36),
      and perioperative death was reported in nine patients (1%). Advantages in favour
      of MIS included reduced hospital stay (median 5 vs 8 days), reduced major blood
      loss (3% vs 14%) and reduced transfusion requirement (6% vs 24%). In all, 76
      cases (8%) were excluded from analysis based on benign pathology leading to
      reassignment to the 'simple nephrectomy' category. CONCLUSIONS: NU is currently a
      low-volume operation (median 3 cases/year) within the remit of the nephrectomy
      surgeon, but is a safe procedure with a relatively low complication rate. Most NU
      surgery in the UK is now performed with laparoscopic assistance, with advantages
      including reduced major blood loss, reduced transfusion requirement and shorter
      hospital stay.

PMID- 24906189
TI  - Raman spectroscopy provides a rapid, non-invasive method for quantitation of
      starch in live, unicellular microalgae.
AB  - Conventional methods for quantitation of starch content in cells generally
      involve starch extraction steps and are usually labor intensive, thus a rapid and
      non-invasive method will be valuable. Using the starch-producing unicellular
      microalga Chlamydomonas reinhardtii as a model, we employed a customized Raman
      spectrometer to capture the Raman spectra of individual single cells under
      distinct culture conditions and along various growth stages. The results revealed
      a nearly linear correlation (R(2) = 0.9893) between the signal intensity at 478
      cm(-1) and the starch content of the cells. We validated the specific correlation
      by showing that the starch-associated Raman peaks were eliminated in a mutant
      strain where the AGPase (ADP-glucose pyrophosphorylase) gene was disrupted and
      consequentially the biosynthesis of starch blocked. Furthermore, the method was
      validated in an industrial algal strain of Chlorella pyrenoidosa. This is the
      first demonstration of starch quantitation in individual live cells. Compared to
      existing cellular starch quantitation methods, this single-cell Raman spectra
      based approach is rapid, label-free, non-invasive, culture-independent, low-cost,
      and potentially able to simultaneously track multiple metabolites in individual
      live cells, therefore should enable many new applications. 

PMID- 24906190
TI  - Descriptions by general practitioners and nurses of their collaboration in
      continuous sedation until death at home: in-depth qualitative interviews in three
      European countries.
AB  - CONTEXT: One palliative care approach that is increasingly being used at home for
      relieving intolerable suffering in terminally ill patients is continuous sedation
      until death. Its provision requires a multidisciplinary team approach, with
      adequate collaboration and communication. However, it is unknown how general
      practitioners (GPs) and home care nurses experience being involved in the use of
      sedation at home. OBJECTIVES: To present case-based GP and nurse descriptions of
      their collaboration, roles, and responsibilities during the process of continuous
      sedation until death at home in Belgium, The Netherlands, and the U.K. METHODS:
      We held in-depth qualitative interviews with 25 GPs and 26 nurses closely
      involved in the care of 29 adult cancer patients who received continuous sedation
      until death at home. RESULTS: We found that, in Belgium and The Netherlands, it
      was the GP who typically made the final decision to use sedation, whereas in the
      U.K., it was predominantly the nurse who both encouraged the GP to prescribe
      anticipatory medication and decided when to use the prescription. Nurses in the
      three countries reported that they commonly perform and monitor sedation in the
      absence of the GP, which they reported to experience as "emotionally burdensome."
      CONCLUSION: We found variety among the countries studied regarding the decision
      making and provision of continuous sedation until death at home. These
      differences, among others, may be the result of different organizational contexts
      in the three countries such as the use of anticipatory medication in the U.K.

PMID- 24906191
TI  - Are mitochondria the Achilles' heel of the Kingdom Fungi?
AB  - A founding event in the origin of eukaryotes is the acquisition of an
      extraordinary organelle, the mitochondrion, which contains its own genome. Being
      linked to energy metabolism, oxidative stress, cell signalling, and cell death,
      the mitochondrion to a certain extent controls life and death in eukaryotic
      cells. The large metabolic diversity and living strategies of the Kingdom Fungi
      make their mitochondria of particular evolutionary interest. The review focuses
      first on the characteristics of mitochondria in the Kingdom Fungi, then on their
      implications in the organism survival, pathogenicity and resistance, and finally
      on proposing unconventional strategies to investigate the biology of fungal
      mitochondria, unveiling the possibility that mitochondria play as the Achilles'
      heel of this kingdom. 

PMID- 24906193
TI  - Increased behavioral output but intact goal-directed and habitual responding for
      food reward following early-life social deprivation in rats.
AB  - Early-life social adversity, such as child neglect and institutionalized rearing,
      is associated with later-life difficulties of inhibitory control that may reflect
      altered attribution of salience to external stimuli. Studies in rats demonstrate
      that early-life social deprivation results in enhanced responsiveness to reward
      stimuli and conditioned reward cues. This study examined whether these effects
      are related to fundamental changes in appetitive conditioning processes involving
      instrumental goal-directed and habitual responding for food reward. Rats were
      reared either by the mother (maternal rearing; MR) or in complete isolation from
      the mother and litter (artificial rearing; AR) and tested as adults in two
      appetitive conditioning tasks. AR and MR rats did not differ in the amount of
      goal-directed effort they exerted to obtain food reward on progressive ratio
      schedules of reinforcement. AR and MR rats also did not differ in the shift from
      goal-directed to habitual responding on a random interval schedule and they were
      equally sensitive to changes in reward value. The major difference between AR and
      MR rats was that AR rats exhibited more non-instrumental responses (empty food
      magazine entries, ineffective lever presses). Thus, early-life social deprivation
      of rats through AR affects the expression of unreinforced extraneous behaviors
      when motivational requirements are high, but does not affect conditioned goal
      directed and habitual responding to reward. The findings have implications for
      understanding what aspects of responsiveness to external stimuli may be
      selectively affected in disorders of inhibition associated with early-life social
      adversity. 

PMID- 24906192
TI  - The conformational and subcellular compartmental dance of plant NLRs during viral
      recognition and defense signaling.
AB  - Plant innate immune response against viruses utilizes intracellular Nucleotide
      Binding domain Leucine Rich Repeat (NLR) class of receptors. NLRs recognize
      different viral proteins termed elicitors and initiate diverse signaling
      processes that induce programmed cell death (PCD) in infected cells and restrict
      virus spread. In this review we describe the recent advances made in the study of
      plant NLRs that detect viruses. We describe some of the physical and functional
      interactions these NLRs undertake. We elaborate on the intra-molecular and
      homotypic association of NLRs that function in self-regulation and activation.
      Nuclear role for some viral NLRs is discussed as well as the emerging importance
      of the RNAi pathway in regulating the NLR family. 

PMID- 24906194
TI  - Facilitating the right but not left DLPFC by TMS decreases truthfulness of object
      naming responses.
AB  - Dorsolateral prefrontal cortex (DLPFC) participates in many mental functions
      involving cognitive control. This also applies to processes underlying deception.
      Recently it was shown that, compared to the opposite effect found with left
      hemisphere 1-Hz repetitive transcranial magnetic stimulation of the DLPFC, right
      hemisphere stimulation decreased the propensity to produce untruthful responses
      in a subsequent task where subjects had freedom to name presented stimulus
      objects either veridically or nonveridically. In a similar experiment, the
      purpose of the present study was to test whether changing the rTMS protocol from
      the disrupting to facilitatory type can lead to opposite results. When trains of
      10-Hz pulses were delivered to the right DLPFC, propensity to lie increased while
      similar left-hemisphere DLPFC stimulation did not change the rate of untruthful
      responses. We can conclude that the way how right DLPFC and other areas
      functionally associated with it are involved in producing truthful or
      deliberately deceptive statements about perceived objects considerably depends on
      what are the parameters of stimulation by which functionality of this system is
      manipulated.

PMID- 24906196
TI  - Enriched environment improves the cognitive effects from traumatic brain injury
      in mice.
AB  - To date, there is yet no established effective treatment (medication or cognitive
      intervention) for post-traumatic brain injury (TBI) patients with chronic
      sequelae. Enriched environment (EE) has been recognized of importance in brain
      regulation, behaviour and physiology. Rodents reared in, or pre-exposed to EE,
      recovered better from brain insults. Using the concussive head trauma model of
      minimal TBI in mice, we evaluated the effect of transition to EE following a
      weight-drop (30g or 50g) induced mTBI on behavioural and cognitive parameters in
      mice in the Novel Object Recognition task, the Y- and the Elevated Plus mazes. In
      all assays, both mTBI groups (30g, 50g) housed in normal conditions were equally
      and significantly impaired 6 weeks post injury in comparison with the no-mTBI
      (p<0.001 and p<0.03, respectively) and the mTBI+EE groups (p<0.001 for the 30g,
      and p<0.017 for the 50g). No differences were found between the control and the
      EE mice. Two separate finding emerge: (1) the significantly positive effects of
      the placement in EE following mTBI, on the rehabilitative process of the tested
      behaviours in the affected mice; (2) the lack of difference between the groups of
      mice affected by 30g or by 50g. Further studies are needed in order to
      characterize the exact pathways involved in the positive effects of the EE on
      mice recovery from mTBI. Possible clinical implications indicate the importance
      of adapting correlates of EE to humans, i.e., prolonged and intensive physical
      activity - possibly combined with juggling training and intensive cognitive
      stimulation.

PMID- 24906195
TI  - Identifying patterns of anxiety and depression in children with chromosome
      22q11.2 deletion syndrome: comorbidity predicts behavioral difficulties and
      impaired functional communications.
AB  - BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex genetic
      disorder with a variable clinical presentation that can include cardiac, neural,
      immunological, and psychological issues. Previous studies have measured elevated
      anxiety and depression in children with 22q11.2DS. Comorbity of anxiety and
      depression is well established in the pediatric literature but the nature of
      comorbidity patterns has not been empirically established in children with
      22q11.2DS. Comorbidity of anxiety and depression has important implications for
      treatment and prognosis, and may be a marker of risk in this population of
      children at high-risk for developing schizophrenia. METHOD: Participants were 131
      boys and girls ages 8-14 with (n=76) and without (n=55) 22q11.2DS and their
      mothers. Children and mothers independently completed self- and parent-report
      measures of anxiety and depression. Mothers also completed measures of behavioral
      functioning including the Behavioral Assessment for Children, 2nd ed. (BASC-2).
      Cluster analyses were conducted to test if theoretically based groupings of
      anxiety and depression could be identified. We hypothesized four psychological
      profiles based on child- and mother-reports: low/no anxiety and low/no
      depression, higher depression and low/no anxiety, higher anxiety and no/low
      depression, and a comorbid profile of higher anxiety and higher depression. BASC
      2 subscale scores were then compared across subgroups of children to determine if
      a comorbid profile would predict greater behavioral difficulties. RESULTS: In the
      full sample of children both with and without 22q11.2DS, cluster analyses of self
      and maternal reported anxiety and depression revealed the expected subgroups: (1)
      a group of children with higher anxiety/lower depression (anxious); (2) a group
      with primary depression (lower anxiety/higher depression (depressed)); (3) a
      comorbid group with higher anxiety/higher depression (comorbid); and, (4) a
      lowest anxiety/lowest depression group (NP). Mothers' reports produced highly
      similar groupings. Furthermore, the 22q11.2DS youth were more likely to be in
      anxiety, depressed or comorbid clusters than the typically developing (TD) youth.
      Children with 22q11.2DS comorbid for anxiety and depression exhibited the worst
      functional outcomes (e.g., poor poorer functional communication, and reduced
      daily life activities). CONCLUSIONS: Anxiety, comorbid with depression may be of
      particular concern in children with 22q11.2DS who arguably carry a greater burden
      on their stress coping resources than children without a complex genetic
      disorder. Furthermore, the manifestation of negative mood, anxiety and difficult
      behavior is likely to reverberate between the child and her or his environment.
      This can lead to negative interactions with family, peers, and teachers, which in
      turn further taxes coping resources. Comorbidity of anxiety and depression within
      a vulnerable population highlights the need for the development of tailored
      interventions.

PMID- 24906197
TI  - Anxiolytic effects of prelimbic 5-HT(1A) receptor activation in the
      hemiparkinsonian rat.
AB  - This study sought to assess whether unilateral lesions of the medial forebrain
      bundle (MFB) using 6-hydroxydopamine in rats are able to induce anxiety-like
      behaviors, the role of serotonin-1A (5-HT1A) receptors of the prelimbic (PrL) sub
      region of ventral medial prefrontal cortex in the regulation of these behaviors,
      the density of 5-HT neurons in the dorsal raphe nucleus (DRN) and co-localization
      of 5-HT1A receptor and neuronal glutamate transporter EAAC1-immunoreactive (EAAC1
      ir) cells in the PrL. Unilaterally lesioning the MFB induced anxiety-like
      behaviors as measured by the open-field and elevated plus maze tests when
      compared to sham-operated rats. Intra-PrL injection of 5-HT1A receptor agonist 8
      OH-DPAT (50, 100, and 500 ng/rat) decreased the percentage of time spent in the
      center of the open-field and percentages of open arm entries and open arm time in
      sham-operated rats, indicating the induction of anxiogenic responses, and
      administration of 5-HT1A receptor antagonist WAY-100635 (60, 120, and 240 ng/rat)
      showed anxiolytic effects. However, 8-OH-DPAT, at the same doses, increased the
      percentage of time spent in the center of the open-field and percentages of open
      arm entries and open arm time in the lesioned rats, indicating the induction of
      anxiolytic effects, and WAY-100635 produced anxiogenic responses. Unilateral MFB
      lesion decreased the density of 5-HT neurons in the DRN, and percentage of EAAC1
      ir cells expressing 5-HT1A receptors in the PrL. These results suggest that
      unilateral lesions of the MFB in rats may induce anxiety-like behaviors, and
      activation of 5-HT1A receptors in the PrL has anxiolytic effects in the rat model
      of Parkinson's disease.

PMID- 24906198
TI  - Effects of voluntary and treadmill exercise on spontaneous withdrawal signs,
      cognitive deficits and alterations in apoptosis-associated proteins in morphine
      dependent rats.
AB  - Chronic exposure to morphine results in cognitive deficits and alterations of
      apoptotic proteins in favor of cell death in the hippocampus, a brain region
      critically involved in learning and memory. Physical activity has been shown to
      have beneficial effects on brain health. In the current work, we examined the
      effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the
      associated cognitive defects, and changes of apoptotic proteins in morphine
      dependent rats. Morphine dependence was induced through bi-daily administrations
      of morphine (10mg/kg) for 10 days. Then, the rats were trained under two
      different exercise protocols: mild treadmill exercise or voluntary wheel exercise
      for 10 days. After exercise training, their spatial learning and memory and
      aversive memory were examined by a water maze and by an inhibitory avoidance
      task, respectively. The expression of the pro-apoptotic protein Bax and the anti
      apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We
      found that chronic exposure to morphine impaired spatial and aversive memory and
      remarkably suppressed the expression of Bcl-2, but Bax expression remained
      constant. Both voluntary and treadmill exercise alleviated memory impairment,
      increased the expression of Bcl-2 protein, and only the later suppressed the
      expression of Bax protein in morphine-dependent animals. Moreover, both exercise
      protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our
      findings showed that exercise reduces the spontaneous morphine-withdrawal signs,
      blocks the associated impairment of cognitive performance, and overcomes morphine
      induced alterations in apoptotic proteins in favor of cell death. Thus, exercise
      may be a useful therapeutic strategy for cognitive and behavioral deficits in
      addict individuals. 

PMID- 24906199
TI  - Augmented tonic pain-related behavior in knockout mice lacking monoacylglycerol
      lipase, a major degrading enzyme for the endocannabinoid 2-arachidonoylglycerol.
AB  - Monoacylglycerol lipase (MGL) is the main enzyme responsible for degradation of
      the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective inhibitors of MGL
      have antinociceptive effects upon acute administration and, therefore, hold
      promise as analgesics. To gain insight into the possible consequences of their
      prolonged administration, genetically modified mice with the knocked-out MGL gene
      were tested in several models of acute (phasic, tonic) and chronic (inflammatory,
      neuropathic) pain. MGL knockout mice showed normal acute phasic pain perception
      (pain thresholds) and no alleviation of pain perception in models of inflammatory
      and neuropathic pain. However, compared with wild-type controls, they showed
      significantly augmented nociceptive behavior in models of acute somatic and
      visceral tonic pain (formalin and acetic acid tests). The observed proalgesic
      changes in perception of tonic pain in MGL knockouts could have resulted from
      desensitization of cannabinoid receptors (known to occur after genetic
      inactivation of MGL). Supporting this notion, chronic pretreatment with the
      selective CB1 receptor antagonist AM 251 (employed to re-sensitize cannabinoid
      receptors in MGL knockouts) resulted in normalization of their tonic pain-related
      behaviors. Similar augmentation of tonic pain-related behaviors was replicated in
      C57BL/6N mice pretreated chronically with the selective MGL inhibitor JZL 184
      (employed to pharmacologically desensitize CB1 receptors). These findings imply
      that prolonged use of MGL inhibitors, at doses causing close to complete
      inhibition of MGL enzymatic activity, not only have no beneficial analgesic
      effects, they may lead to exacerbation of some types of pain (particularly those
      with a tonic component). 

PMID- 24906201
TI  - Synthesis, structural and photo-physical studies of bismuth(III) complexes with
      Janus scorpionate and co-ligands.
AB  - Some novel complexes of bismuth(III) with the Janus scorpionate ligand
      [HB(mtda(Me))3](-) (mtda(Me) = 2-mercapto-5-methyl-1,3,4-thiadiazolyl) were
      synthesised. Na[HB(mtda(Me))3] (1) was reacted with BiX3 (X = Cl, I, NO3) in the
      molar ratio 2 : 1 to afford the bismuth complexes {HB(mtda(Me))3}2BiCl (3),
      Na[{HB(mtda(Me))3}2BiI2] (4) and [{HB(mtda(Me))3}2Bi(NO3)]n (5). Two mixed
      complexes {HB(mtda(Me))3}Bi(phen)Cl2 (6) and {HB(mtda(Me))3}Bi(bipy)Cl2 (7) were
      obtained using Janus scorpionate as the primary ligand in the presence of 1,10
      phenanthroline and 2,2'-bipyridyl, respectively, as co-ligands in the 1 : 1
      ratio. The obtained complexes were characterised by (1)H, (13)C and diffusion NMR
      (DOSY), elemental analyses and mass spectrometry. Structures of the compounds
      NBu4[HB(mtda(Me))3] (2), 3, 4, 5, 6 and 7 were determined by single crystal X-ray
      diffraction. The molecular dynamic process in complex 3 was also studied by
      variable temperature NMR measurements. All bismuth complexes, except for the
      polymeric 5, are monomeric. Complexes 6 and 7 exhibit (B)H...Bi distances of
      2.76(3) and 2.71(2) A length, respectively. Compounds 2, 6 and 7 were screened
      for their luminescence activity. At 77 K in ethanol solution, complexes 6 and 7
      exhibit phosphorescence from ligand-to-ligand charge transfer (LLCT) and the
      ligand-centred (LC) excited state, respectively.

PMID- 24906200
TI  - Exploring strain-promoted 1,3-dipolar cycloadditions of end functionalized
      polymers.
AB  - Strain-promoted 1,3-dipolar cycloaddition of cyclooctynes with 1,3-dipoles such
      as azides, nitrones, and nitrile oxides, are of interest for the
      functionalization of polymers. In this study, we have explored the use of a 4
      dibenzocyclooctynol (DIBO)-containing chain transfer agent in reversible addition
      fragmentation chain transfer polymerizations. The controlled radical
      polymerization resulted in well-defined DIBO-terminating polymers that could be
      modified by 1,3-dipolar cycloadditions using nitrones, nitrile oxides, and azides
      having a hydrophilic moiety. The self-assembly properties of the resulting block
      copolymers have been examined. The versatility of the methodology was further
      demonstrated by the controlled preparation of gold nanoparticles coated with the
      DIBO-containing polymers to produce materials that can be further modified by
      strain-promoted cycloadditions. 

PMID- 24906202
TI  - Pediatric psycho-oncology care: standards, guidelines, and consensus reports.
AB  - OBJECTIVE: The aim of this study was to identify existing guidelines, standards,
      or consensus-based reports for psychosocial care of children with cancer and
      their families. PURPOSE: Psychosocial standards of care for children with cancer
      can systematize the approach to care and create a replicable model that can be
      utilized in pediatric hospitals around the world. Determining gaps in existing
      standards in pediatric psycho-oncology can guide development of useful evidence
      based and consensus-based standards. METHODS: The MEDLINE and PubMed databases
      were searched by investigators at two major pediatric oncology centers for
      existing guidelines, consensus-based reports, or standards for psychosocial care
      of patients with pediatric cancer and their families published in peer-reviewed
      journals in English between 1980 and 2013. RESULTS: We located 27 articles about
      psychosocial care that met inclusion criteria: 5 set forth standards, 19 were
      guidelines, and 3 were consensus-based reports. None was sufficiently up to date,
      comprehensive, specific enough, or evidence- or consensus-based to serve as a
      current standard for psychosocial care for children with cancer and their
      families. CONCLUSION: Despite calls by a number of international pediatric
      oncology and psycho-oncology professional organizations about the urgency of
      addressing the psychosocial needs of the child with cancer to reduce suffering,
      there remains a need for development of a widely acceptable, evidence-based and
      consensus-based, comprehensive standard of care to guide provision of essential
      psychosocial services to all patients with pediatric cancer.

PMID- 24906203
TI  - Autocrine interleukin-6 drives skin-derived mesenchymal stem cell trafficking via
      regulating voltage-gated Ca(2+) channels.
AB  - Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential
      for a variety of diseases including autoimmune disorders. A fundamental
      requirement for MSC-mediated in vivo immunosuppression is their effective
      trafficking. However the mechanism underlying MSC trafficking remains elusive.
      Here we report that skin-derived MSCs (S-MSCs) secrete high levels of interleukin
      6 (IL-6) in inflammatory conditions. Disruption of the il6 or its signaling
      transducer gp130 blocks voltage-gated calcium (Ca(2+) ) channels (VGCC)
      critically required for cell contraction involved in the sequential adhesion and
      de-adhesion events during S-MSC migration. Deletion of il6 gene leads to a severe
      defect in S-MSC's trafficking and immunosuppressive function in vivo. Thus, this
      unexpected requirement of autocrine IL-6 for activating Ca(2+) channels uncovers
      a previously unrecognized link between the IL-6 signaling and the VGCC and
      provides novel mechanistic insights for the trafficking and immunomodulatory
      activities of S-MSCs.

PMID- 24906204
TI  - Bone morphogenetic protein-10 induces cardiomyocyte proliferation and improves
      cardiac function after myocardial infarction.
AB  - Heart disease is among the leading causes of death worldwide, and the limited
      proliferation of mammalian cardiomyocytes prevents heart regeneration in response
      to injury. Bone morphogenetic protein-10 (BMP10) exerts multiple roles in various
      developmental events; however, the effect of BMP10 and the underlying mechanism
      involved in cardiac repair remains unclear. After stimulation with the
      recombinant BMP10, an obvious dose-dependent cardiomyocyte proliferation and
      reentry of differentiated mammalian cardiomyocytes into the cell cycle was
      observed. Furthermore, BMP10 stimulation strikingly enhanced Tbx20 expression.
      Further analysis demonstrated that T-box 20 (Tbx20) was involved in BMP10-induced
      proliferation of differentiated cardiomyocytes as preconditioning with Tbx20
      siRNA significantly attenuated BMP10-induced DNA synthesis. In vivo, BMP10
      induced rat cardiomyocyte DNA synthesis and cytokinesis. After myocardial
      infarction (MI), BMP10 stimulated cardiomyocyte cell-cycle reentry and mitosis,
      resulting in the decrease of infarct size and improvement of cardiac repair.
      Taken together, these data indicated that BMP10 stimulated cardiomyocyte
      proliferation and repaired cardiac function after heart injury. Consequently,
      BMP10 may be a potential target for innovative strategies against heart failure.

PMID- 24906206
TI  - Structural characterisation of a layered double hydroxide nanosheet.
AB  - We report the atomic-scale structure of a Zn152Al-borate layered double hydroxide
      (LDH) nanosheet, as determined by reverse Monte Carlo (RMC) modelling of X-ray
      total scattering data. This study involves the extension of the RMC method to
      enable structural refinement of two-dimensional nanomaterials. The refined LDH
      models show the intra-layer geometry in this highly-exfoliated phase to be
      consistent with that observed in crystalline analogues, with the reciprocal-space
      scattering data suggesting a disordered arrangement of the Zn(2+) and Al(3+)
      cations within the nanosheet. The approach we develop is generalisable and so
      offers a method of characterising the structures of arbitrary nanosheet phases,
      including systems that support complex forms of disorder within the nanosheets
      themselves.

PMID- 24906205
TI  - Comparison of the impact of high-flux dialysis on mortality in hemodialysis
      patients with and without residual renal function.
AB  - BACKGROUND: The effect of flux membranes on mortality in hemodialysis (HD)
      patients is controversial. Residual renal function (RRF) has shown to not only be
      as a predictor of mortality but also a contributor to beta2-microglobulin
      clearance in HD patients. Our study aimed to determine the interaction of
      residual renal function with dialyzer membrane flux on mortality in HD patients.
      METHODS: HD Patients were included from the Clinical Research Center registry for
      End Stage Renal Disease, a prospective observational cohort study in Korea. Cox
      proportional hazards regression models were used to study the association between
      use of high-flux dialysis membranes and all-cause mortality with RRF and without
      RRF. The primary outcome was all-cause mortality. RESULTS: This study included
      893 patients with 24 h-residual urine volume >=100 ml (569 and 324 dialyzed using
      low-flux and high-flux dialysis membranes, respectively) and 913 patients with 24
      h-residual urine volume <100 ml (570 and 343 dialyzed using low-flux and high
      flux dialysis membranes, respectively). After a median follow-up period of 31
      months, mortality was not significantly different between the high and low-flux
      groups in patients with 24 h-residual urine volume >=100 ml (HR 0.86, 95% CI,
      0.38-1.95, P = 0.723). In patients with 24 h-residual urine volume <100 ml, HD
      using high-flux dialysis membrane was associated with decreased mortality
      compared to HD using low-flux dialysis membrane in multivariate analysis (HR
      0.40, 95% CI, 0.21-0.78, P = 0.007). CONCLUSIONS: Our data showed that HD using
      high-flux dialysis membranes had a survival benefit in patients with 24 h
      residual urine volume <100 ml, but not in patients with 24 h-residual urine
      volume >=100 ml. These findings suggest that high-flux dialysis rather than low
      flux dialysis might be considered in HD patients without RRF.

PMID- 24906207
TI  - Evaluation of clinical efficacy and safety of cervical trauma collars:
      differences in immobilization, effect on jugular venous pressure and patient
      comfort.
AB  - BACKGROUND: Concern has been raised that cervical collars may increase
      intracranial pressure in traumatic brain injury. The purpose of this study was to
      compare four types of cervical collars regarding efficacy of immobilizing the
      neck, effect on jugular venous pressure (JVP), as a surrogate for possible effect
      on intracranial pressure, and patient comfort in healthy volunteers. METHODS: The
      characteristics of four widely used cervical collars (Laerdal Stifneck((r)) (SN),
      Vista((r)) (VI), Miami J Advanced((r)) (MJ), Philadelphia((r)) (PH)) were studied
      in ten volunteers. Neck movement was measured with goniometry, JVP was measured
      directly through an endovascular catheter and participants graded the collars
      according to comfort on a scale 1-5. RESULTS: The mean age of participants was 27
      +/- 5 yr and BMI 26 +/- 5. The mean neck movement (53 +/- 9 degrees ) decreased
      significantly with all the collars (p < 0.001) from 18 +/- 7 degrees  to 25 +/- 9
      degrees  (SN < MJ < PH < VI). There was a significant increase in mean JVP (9.4
      +/- 1.4 mmHg) with three of the collars, but not with SN, from 10.5 +/- 2.1 mmHg
      to 16.3 +/- 3.3 mmHg (SN < MJ < VI < PH). The grade of comfort between collars
      varied from 4.2 +/- 0.8 to 2.2 +/- 0.8 (VI > MJ > SN > PH). CONCLUSION: Stifneck
      and Miami J collars offered the most efficient immobilization of the neck with
      the least effect on JVP. Vista and Miami J were the most comfortable ones. The
      methodology used in this study may offer a new approach to evaluate clinical
      efficacy and safety of neck collars and aid their continued development.

PMID- 24906208
TI  - Economic downturns and male cesarean deliveries: a time-series test of the
      economic stress hypothesis.
AB  - BACKGROUND: In light of the recent Great Recession, increasing attention has
      focused on the health consequences of economic downturns. The perinatal
      literature does not converge on whether ambient economic declines threaten the
      health of cohorts in gestation. We set out to test the economic stress hypothesis
      that the monthly count of cesarean deliveries (CD), which may gauge the level of
      fetal distress in a population, rises after the economy declines. We focus on
      male CD since the literature reports that male more than female fetuses appear
      sensitive to stressors in utero. METHODS: We tested our ecological hypothesis in
      California for 228 months from January 1989 to December 2007, the most recent
      data available to us at the time of our tests. We used as the independent
      variable the Bureau of Labor Statistics unadjusted total state employment series.
      Time-series methods controlled for patterns of male CD over time. We also
      adjusted for the monthly count of female CD, which controls for well
      characterized factors (e.g., medical-legal environment, changing risk profile of
      births) that affect CD but are shared across infant sex. RESULTS: Findings
      support the economic stress hypothesis in that male CD increases above its
      expected value one month after employment declines (employment coefficient = 
      24.09, standard error = 11.88, p = .04). Additional exploratory analyses at the
      metropolitan level indicate that findings in Los Angeles and Orange Counties
      appear to drive the State-level relation. CONCLUSIONS: Contracting economies may
      perturb the health of male more than female fetuses sufficiently enough to
      warrant more CD. Male relative to female CD may sensitively gauge the cohort
      health of gestations.

PMID- 24906210
TI  - Caring for children and adolescents with epilepsy: creating an innovative
      electronic educational resource.
AB  - The majority of children and adolescents with epilepsy are managed in the
      community setting by general paediatricians. However, there is a paucity of
      practical, relevant information and standardised management documents assisting
      paediatricians. In the era of sub-specialisation, an electronic educational
      resource developed by specialists in epilepsy and paediatrics enhances the
      interface between tertiary and secondary/primary care. We aimed to create a
      website (www.pennsw.com.au) designed to optimise the care of all children and
      adolescents living with epilepsy and to assess its clinical usefulness. The site
      provides clinicians and families an aligned resource, including key information
      on epilepsy syndromes, medication usage and adverse effects, safety (sleep
      deprivation, water sports), driving, pregnancy, psychosocial impact of epilepsy
      and coping skills. General paediatricians and carers completed a questionnaire,
      utilising rating scales and open ended questions, to evaluate design, content and
      clinical usefulness. Forty-nine general paediatricians with a median 12 years of
      paediatric practice participated. Thirty-two carers participated. Epilepsy
      syndrome was focal in 59% of the children and generalised in 41%. The majority of
      participants (paediatricians: 84-100%, families: 69-100%) rated the website as
      well designed, practical, informative and clinically useful. General
      paediatricians considered the "Medication" pages and "Epilepsy Management
      Documents" as practically useful. Carers recorded the "Family Resources", seizure
      recording documents, the support information on mental health, and the "Coping
      with Epilepsy" segment as most informative. General paediatricians and carers
      highly valued the website, reflected by 120,000 page views in 12 months since its
      launch.

PMID- 24906209
TI  - Age-dependent sensitization of cutaneous nociceptors during developmental
      inflammation.
AB  - BACKGROUND: It is well-documented that neonates can experience pain after injury.
      However, the contribution of individual populations of sensory neurons to
      neonatal pain is not clearly understood. Here we characterized the functional
      response properties and neurochemical phenotypes of single primary afferents
      after injection of carrageenan into the hairy hindpaw skin using a neonatal ex
      vivo recording preparation. RESULTS: During normal development, we found that
      individual afferent response properties are generally unaltered. However, at the
      time period in which some sensory neurons switch their neurotrophic factor
      responsiveness, we observe a functional switch in slowly conducting, broad
      spiking fibers ("C"-fiber nociceptors) from mechanically sensitive and thermally
      insensitive (CM) to polymodal (CPM). Cutaneous inflammation induced prior to this
      switch (postnatal day 7) specifically altered mechanical and heat responsiveness,
      and heat thresholds in fast conducting, broad spiking ("A"-fiber) afferents.
      Furthermore, hairy skin inflammation at P7 transiently delayed the functional
      shift from CM to CPM. Conversely, induction of cutaneous inflammation after the
      functional switch (at P14) caused an increase in mechanical and thermal
      responsiveness exclusively in the CM and CPM neurons. Immunocytochemical analysis
      showed that inflammation at either time point induced TRPV1 expression in
      normally non-TRPV1 expressing CPMs. Realtime PCR and western blotting analyses
      revealed that specific receptors/channels involved in sensory transduction were
      differentially altered in the DRGs depending on whether inflammation was induced
      prior to or after the functional changes in afferent prevalence. CONCLUSION:
      These data suggest that the mechanisms of neonatal pain development may be
      generated by different afferent subtypes and receptors/channels in an age-related
      manner.

PMID- 24906211
TI  - Hypokalemia and hypomagnesaemia related to levetiracetam use.
AB  - Levetiracetam (LEV), used for both partial and generalized seizures, is a
      frequently preferred antiepileptic because of its few side effects. We present a
      23-year-old man who developed hypokalemia after switching from valproate to LEV.
      The patient was sent to our clinic due to hypokalemia 1 month after initiation of
      LEV, and his neurological examination was normal. Further examinations revealed
      hypokalemia (3.1 mmol/L) and hypomagnesaemia (0.56 mmol/L). His hemogram, blood
      urea nitrogen, creatinine, total cortisol, thyroid function tests, creatinine
      clearance, and renal Doppler ultrasound were normal. LEV was tapered off and
      treatment with 200mg/day lamotrigine begun. Potassium and magnesium levels
      returned to normal ranges in subsequent tests. While hypokalemia and
      hypomagnesaemia have not been reported before to our knowledge, interstitial
      nephritis and renal failure after the use of LEV have been. Hypokalemia, found in
      the early period in this case, may be an indicator of a recently developed renal
      tubular disorder. This experience indicates that unpredictable side effects of
      increasingly used new antiepileptic drugs should be taken into consideration.

PMID- 24906212
TI  - Special issue on the Challenges in Environmental Science and Engineering, CESE
      2013: 29 Oct.-2 Nov., EXCO, Daegu, South Korea. Preface.

PMID- 24906213
TI  - Special issue on International Conference on Advances in Biotechnology and
      Bioinformatics 2013. Preface.

PMID- 24906215
TI  - Pattern and associated factors of potential drug-drug interactions in both pre-
      and early post-hematopoietic stem cell transplantation stages at a referral
      center in the Middle East.
AB  - The aim of this study was to determine the pattern as well as associated factors
      of moderate and major potential drug-drug interactions (PDDIs) in both the pre-
      and early post-transplantation stages at a referral hematopoietic stem cell
      transplantation (HSCT) center. All adolescents and adults undergone HSCT within a
      3-year period were screened retrospectively for potential moderate or severe
      PDDIs by the Lexi-Interact On-Desktop software. Among 384 patients, a total of
      13,600 PDDIs were detected. The median (interquartile range) cumulative PDDIs
      burden was 41 (28). All (100 %) individuals experienced at least one PDDI. More
      than four fifths (81.8 %) of detected PDDIs were moderate. The predominant
      mechanism of PDDIs was pharmacokinetics (54.3 %). Interaction between
      sulfamethoxazole-trimethoprim and fluconazole was the most common PDDIs involving
      95.3 % of the study population. More than three fifths (61.5 %) of detected PDDIs
      were caused by HSCT-related medications. No interaction was identified between
      two anticancer agents. Interactions of cyclophosphamide with phenytoin, busulfan
      with metronidazole, dexamethasone, or clarithromycin were the only detected PDDI
      between anticancer and non-anticancer medications. Type of HSCT and the numbers
      of administered medications were significantly associated with major PDDIs. The
      epidemiology, real clinical consequence, and economic burden of DDIs on patients
      undergone HSCT particularly around the transplantation period should be assessed
      further by prospective, multicenter studies.

PMID- 24906214
TI  - A model-based cost-effectiveness analysis of a grommets-led care pathway for
      children with cleft palate affected by otitis media with effusion.
AB  - There is a paucity of evidence to guide the management of otitis media with
      effusion (OME), which is a common problem causing significant hearing impairment
      in children with cleft palate. The insertion of grommets is currently being used
      to correct hearing impairment and prevent complications of unmanaged OME, but
      there is ongoing discussion about whether the benefits of grommets outweigh the
      costs and risks. A decision-tree model was developed to assess the surgical
      insertion of grommets with two non-surgical alternatives (hearing-aids and do
      nothing strategies) in cleft palate children with persistent bilateral OME. The
      model assumed a 2-year time horizon and a UK National Health Service perspective.
      Outcomes were valued using quality-adjusted life-years (QALYs) estimated by
      linking utility values with potential hearing gains measured in decibels.
      Multiple data sources were used, including reviews of the clinical effectiveness,
      resource use and utility literature, and supplemented with expert opinion.
      Uncertainty in the model parameters was assessed using probabilistic sensitivity
      analysis. Expected value of perfect information analysis was used to calculate
      the potential value of future research. The results from the probabilistic
      sensitivity analysis indicated that the grommets strategy was associated with an
      incremental cost-effectiveness ratio of L9,065 per QALY gained compared with the
      do-nothing strategy, and the hearing-aids strategy was extended dominated by the
      grommets strategy. The population expected value of perfect information was
      L5,194,030 at a willingness to pay threshold of L20,000 per QALY, implying that
      future research could be potentially worthwhile. This study found some evidence
      that the insertion of grommets to manage cleft palate children with bilateral OME
      is likely to be cost-effective, but further research is required to inform this
      treatment choice. 

PMID- 24906216
TI  - Adding ascorbic acid to arsenic trioxide produces limited benefit in patients
      with acute myeloid leukemia excluding acute promyelocytic leukemia.
AB  - Arsenic trioxide (ATO) is highly effective in acute promyelocytic leukemia (APL),
      but despite its multiple mechanism of action, it has no activity in acute myeloid
      leukemia (AML) that excludes APL (non-APL AML). Ascorbic acid (AA) and ATO
      induces apoptosis in AML cell lines by depleting intracellular glutathione and
      generation of reactive oxygen species. In this study, we evaluated the effect of
      ATO plus AA in patients with non-APL AML. The study enrolled patient aged 18 or
      older with relapsed or refractory AML (non-APL) after conventional chemotherapy
      or previously untreated patients 55 years or older who were unfit for standard
      induction chemotherapy for AML. Intravenous ATO (0.25 mg/kg/day over 1-4 h) was
      given with intravenous AA (1 g/day over 30 min after ATO) for 5 days a week for 5
      weeks (25 doses). Eleven AML patients were enrolled, including six previously
      untreated elderly patients aged 66-84 years in whom five had antecedent
      hematological disorder (ADH). Among 10 evaluable patients, one achieved a CR one
      a CRi and 4 patients had disappearance of blasts from peripheral blood and bone
      marrow. Five of the six responders were seen in previously untreated elderly
      patients. ATO related toxicity was mild. The combination of ATO and AA has
      limited clinical meaningful antileukemia activity in patients with non-APL AML.

PMID- 24906218
TI  - The validation of a novel method combining both HER2 immunohistochemistry and
      HER2 dual-colour silver in situ hybridization on one slide for gastric carcinoma
      testing.
AB  - BACKGROUND: HER2 status assessment is a prerequisite for the establishment of an
      appropriate treatment strategy in gastric cancer. Gastric cancers are very
      heterogeneous and separate evaluations of gene amplification and protein
      expression lead to uncertainties in localizing distinct clones and are time
      consuming. This study evaluates the equivalence of the novel method combining
      both gene and protein platforms on one slide. METHODS: Immunohistochemistry (IHC)
      and HER2 dual-colour silver in situ hybridization (SISH) as single methods
      (IHC/SISH) and gene-protein platform combining both methods on one slide
      (gene/protein) were performed in randomly collected 100 cases of gastric
      adenocarcinoma. Results of IHC/SISH were compared with gene/protein staining.
      RESULTS: 96 of 100 samples were assessable. In the gene/protein staining,
      pathologists were able to assess gene amplification and consequent protein
      expression at the single cell level. In comparison trials, gene amplification was
      observed in 14.6% by both, conventional SISH and gene/protein platform (agreement
      100%; Kappa-coefficient kappa = 1.0). Protein expression scores by IHC were 70.8%
      (0), 10.4% (1+), 9.4% (2+), and 9.4% (3+). Protein expression by gene/protein
      method were: 70.8% (0), 11.5% (1+), 7.3% (2+) and 10.4% (3+) of patients. There
      were complete concordances in IHC assessment of cases with score 0 (100.0%; kappa
      = 1). High concordances are shown in score 1+ (98.96%; kappa = 0.947) and 3+
      (96.88%; kappa = 0.825) cases and good concordances in 2+ cases (95.83%; kappa =
      0.728). CONCLUSIONS: This novel combined platform has the advantage of being able
      to evaluate both gene and the protein status in the same cancer cell and may be
      of particular interest for research and patient's care. ARTICLE CATEGORY: Disease
      Biomarker.

PMID- 24906219
TI  - Prefrontal glutamate levels differentiate early phase schizophrenia and
      methamphetamine addiction: a (1)H MRS study at 3Tesla.
AB  - Acute symptoms of methamphetamine-induced psychosis are similar to those of
      primary schizophrenia. Understanding similarities or differences in the
      biological substrate of these psychoses could lead to early differentiation of
      these two clinical conditions resulting in more efficient treatment strategies.
      Proton magnetic resonance spectroscopy was acquired from the medial prefrontal
      cortex in 29 unmedicated patients with first episode of psychosis (FEP), 29
      abstinent methamphetamine-addicted people (METH) and 45 healthy controls (HCs)
      (age range 17.3 to 29.9years old). The METH group displayed robust reductions in
      concentration levels of glutamate (Glu) relative to FEP (Cohen's d=1.20) and HC
      (d=0.87). The METH group also displayed reduced levels of N-acetylaspartate (NAA)
      relative to FEP (d=0.53) and HC (d=0.76). The HC group displayed a positive
      association between levels of Glu and NAA, r(45)=0.52, p<0.001, while the two
      clinical groups failed to show this normal association. This suggests that the
      cellular metabolism is altered in both conditions. These data support the
      assumption that cellular abnormalities differ between primary schizophrenia and
      methamphetamine addiction despite the overlap in clinical presentation. 

PMID- 24906217
TI  - Dynamic speech representations in the human temporal lobe.
AB  - Speech perception requires rapid integration of acoustic input with context
      dependent knowledge. Recent methodological advances have allowed researchers to
      identify underlying information representations in primary and secondary auditory
      cortex and to examine how context modulates these representations. We review
      recent studies that focus on contextual modulations of neural activity in the
      superior temporal gyrus (STG), a major hub for spectrotemporal encoding. Recent
      findings suggest a highly interactive flow of information processing through the
      auditory ventral stream, including influences of higher-level linguistic and
      metalinguistic knowledge, even within individual areas. Such mechanisms may give
      rise to more abstract representations, such as those for words. We discuss the
      importance of characterizing representations of context-dependent and dynamic
      patterns of neural activity in the approach to speech perception research. 

PMID- 24906220
TI  - Clozapine directly increases insulin and glucagon secretion from islets:
      implications for impairment of glucose tolerance.
AB  - Second generation antipsychotics cause derangements in glucose metabolism that
      are often interpreted as insulin resistance. In previous studies we have shown
      that this is not classical insulin resistance but the drugs were actually
      inducing a hyperglycaemic state associated with elevated hepatic glucose output
      (HGO) and increased levels of glucagon and insulin. However, it remains unclear
      whether these effects are directly elicited by drug actions in the liver and
      pancreas, or whether they are indirectly mediated. Here we investigated if
      clozapine is capable of inducing insulin resistance in the liver or enhancing
      insulin and glucagon secretion from the pancreas. It was observed that insulin
      signalling was elevated in livers from animals treated with clozapine indicating
      there was no insulin resistance in the early steps of insulin signalling. To
      explore whether the defects arise at later stages of insulin action we used an
      isolated perfused liver system. In this model, clozapine had no direct effect on
      insulin's counter regulatory effect on epinephrine-induced HGO. In isolated mouse
      islets clozapine significantly increased glucose-stimulated insulin secretion
      while simultaneously blocking glucose-induced reductions in glucagon secretion.
      We also show that the non-peptidic glucagon receptor like peptide-1 (GLP-1)
      receptor agonist Boc5 was able to overcome the inhibitory effects of clozapine on
      glucose metabolism. Taken together these results suggest that clozapine does not
      have any direct effect on glucose metabolism in the liver but it simultaneously
      stimulates insulin and glucagon secretion, a situation that would allow for the
      concurrent presence of high glucose and high insulin levels in treated animals. 

PMID- 24906221
TI  - Mean platelet volume in schizophrenia unaltered after 1year of clozapine
      exposure.
AB  - This study investigated the MPV of patients with major psychoses before and after
      1year of clozapine exposure. Data were obtained from chart reviews of patients
      who were initiated on clozapine at the Centre of Addiction and Mental Health
      (CAMH) in Toronto. 100 patients were eligible for this study; 65 remained on
      clozapine after 1year. Prior to clozapine initiation, MPV was 10.79+/-0.91fL and
      there was no difference in MPV after 1year of clozapine exposure (p=0.777). We
      found high MPV in patients with schizophrenia and related psychoses, which was
      unaltered after 1year of clozapine treatment. 

PMID- 24906223
TI  - Institutional and production characteristics among smallholder pig producers in
      Enugu State, Nigeria.
AB  - A study on the institutional and production characteristics of pig farming in
      Enugu State, Nigeria, was conducted using 80 randomly selected smallholder pig
      producers. Data were collected by using an interview schedule. Descriptive
      statistics were used to analyze data. The mean number of pigs owned by
      smallholder producer was 18. Only 20.0 and 6.3 % of the producers had access to
      credit and to extension services, respectively. Ninety percent of the respondents
      practiced intensive management system. The major housing type used by producers
      was cement brick walls with aluminum roofing sheets (97.6 %). The majority (80 %)
      of producers reared mostly crossbred pigs and family labor (68.7 %) was most
      prevalent. Fourteen (50 %) of the 28 routine management practices were always
      performed by the pig producers. Extension service providers should intensify
      efforts to provide producers with appropriate management practices and training
      for effective disease control and improve productivity.

PMID- 24906224
TI  - The influence of filament elasticity on transients after sudden alteration of
      length of muscle or load.
AB  - The duration of phase 2 of a transient after sudden reduction of the length of a
      muscle or a load on it decreases rapidly with increasing amplitude of the jump.
      This is mainly due to the increasing role of the superfast relaxation processes
      with a characteristic time of about 0.1 ms. Mainly in order to explain this
      effect, Huxley and Simmons proposed their famous model of force generation in
      1971. The present paper examines the effect of elasticity of filaments on
      relaxation processes. It is shown that if the filaments are not perfectly
      elastic, the superfast tension transient may result from a delay of
      redistribution of stresses within actin and/or myosin filaments at the beginning
      of phase 2. Corresponding redistribution of deformations within the actin
      filaments leads to non-uniform shifts of the attached myosin heads and changes in
      the X-ray diffraction pattern. Additionally, we discuss a change in the
      experimental technique that allows suppression of the elastic vibrations that
      obscure the contributions of other sources to the superfast tension transient. 

PMID- 24906222
TI  - Spousal involvement and CPAP adherence: a dyadic perspective.
AB  - Poor adherence to continuous positive airway pressure (CPAP) treatment is
      associated with substantial health care costs, morbidity and mortality, and has
      been a leading obstacle in the effective management of obstructive sleep apnea
      (OSA). Successful interventions to improve CPAP adherence may ultimately include
      a variety of components. For patients living with spouses (refers to all domestic
      partners), the spouse will likely be an integral component to any successful
      intervention. Developing understanding of the role of spouses in adherence to
      CPAP has been identified to be a critical research need. This review expands the
      investigation of CPAP adherence to a broader context, from an exclusive focus on
      individual patients to a dyadic perspective encompassing both patients and their
      spouses. A conceptual framework based on social support and social control
      theories is proposed to understand spousal involvement in CPAP adherence.
      Methodologies for future investigations are discussed, along with implications
      for developing interventions that engage both patients and their spouses to
      improve CPAP use. 

PMID- 24906226
TI  - Mucosal melanoma of the nasal cavity and paranasal sinuses.
AB  - Mucosal melanoma of the nasal cavity and paranasal sinuses is a rare disease, but
      its incidence appears to be increasing. The mean age at diagnosis is between 65
      and 70 years. Unilateral nasal obstruction and epistaxis are the most common
      presenting complaints. Melanoma arises in the septum or lateral wall of the nasal
      cavity in the great majority of cases. The histological diagnosis is based on
      specific immunohistochemical labelling and is usually established at an advanced
      stage of disease: stage T3 or T4 tumours according to the 7th edition of the
      American Joint Committee on Cancer (AJCC) classification of tumours. First-line
      treatment consists of surgery. The place of intranasal endoscopic surgery remains
      controversial due to the difficulty of controlling surgical margins and should be
      reserved for experienced teams. Adjuvant radiotherapy is usually performed due to
      its efficacy on local and regional disease control. Five-year overall survival of
      mucosal melanoma of the nasal cavity and paranasal sinuses in the most recent
      series does not exceed 40%. Local recurrence is observed in about 50% of cases
      and metastatic disease is common. The quality of initial tumour resection with
      negative surgical margins is the most important prognostic factor for tumours
      confined to the nasal cavity. Hopes for improvement of survival are based on
      early diagnosis, progress in radiotherapy techniques and cell and gene therapy
      that are currently under evaluation.

PMID- 24906225
TI  - Dye-release assay for investigation of antimicrobial peptide activity in a
      competitive lipid environment.
AB  - A dye-release method for investigating the effect of a competitive lipid
      environment on the activity of two membrane-disrupting antimicrobial peptides
      (AMP), maculatin 1.1 and aurein 1.2, is presented. The results support the
      general conclusion that AMP have greater affinity for negatively charged
      membranes, for example bacterial membranes, than for the neutral membrane surface
      found in eukaryotic cells, but only within a competitive lipid environment.
      Indeed, in a single-model membrane environment, both peptides were more potent
      against neutral vesicles than against charged vesicles. The approach was also
      used to investigate the effect of pre-incubating the peptides in a neutral lipid
      environment then introducing charged lipid vesicles. Maculatin was shown to
      migrate from the neutral lipid bilayers, where pores had already formed, to the
      charged membrane bilayers. This result was also observed for charged-to-charged
      bilayers but, interestingly, not for neutral-to-neutral lipid interfaces. Aurein
      was able to migrate from either lipid environment, indicating weaker binding to
      lipid membranes, and a different molecular mechanism for lysis of lipid bilayers.
      Competitive lipid environments could be used to assess other critical conditions
      that modulate the activity of membrane peptides or proteins. 

PMID- 24906227
TI  - Low expression of activating transcription factor 3 in human hepatocellular
      carcinoma and its clinicopathological significance.
AB  - BACKGROUND AND AIM: To explore the expression and role of activating
      transcription factor 3 in human hepatocellular carcinoma. METHODS:
      Immunohistochemistry, Western blot assay and Real-time PCR were used to evaluate
      activating transcription factor 3 protein and gene level in HCC clinical samples.
      RESULTS: Activating transcription factor 3 expression is lowest in HCC, and the
      protein level is lower in patients with capsule invasion, while there is no
      association with other main clinical pathological features. CONCLUSIONS: Low
      expression of ATF3 may function as a tumor suppressor during human hepatocellular
      oncogenesis and targeting ATF3 pathway might be beneficial for anti-HCC therapy.

PMID- 24906228
TI  - Immunoreactivity using anti-ERG monoclonal antibodies in sarcomas is influenced
      by clone selection.
AB  - The aim of the present study was to explore ERG immunoreactivity in a series of
      sarcomas, GIST and malignant rhabdoid tumor (MRT), considering the not fully
      elucidated specificity and sensitivity of this antibody. Paraffin-embedded tissue
      microarrays from those tumors were stained with anti-ERG against the C-terminus
      [(EPR3864(2)] and N-terminus (Clone 9FY). EPR3864(2) was positive in almost all
      angiosarcomas, and MRT.GIST were positive in a large proportion of cases (38.4%),
      and more than half the synovial sarcomas (52.7%) revealed EPR3864(2) staining.
      Several chondrosarcomas, osteosarcomas, rhabdomyosarcoma and Ewing's sarcoma
      family of tumors (ESFT) presented EPR3864(2) expression in a lower number of
      cases. 9FY was positive in most of the angiosarcomas; however, only sporadic ESFT
      and synovial sarcoma were positive and the other tumors tested were negative.
      Fourteen ESFT with EWSR1/Fli-1 gene fusion presented positive nuclear staining
      for EPR3864(2). Similarly, 5 ESFT with EWSR1/Fli-1 gene fusion presented positive
      staining for 9FY. We must stress that the difference between the present and
      previous studies may be due to the source of the anti-ERG employed, anti-ERG
      against C or N-terminus, protein cross-reactivity and dilution. In conclusion,
      specificity for ERG staining in sarcomas should be considered with caution and
      the immunoexpression is undoubtedly influenced by clone and antibody selection. 

PMID- 24906229
TI  - How funding agencies can support research use in healthcare: an online province
      wide survey to determine knowledge translation training needs.
AB  - BACKGROUND: Health research funding agencies are increasingly promoting evidence
      use in health practice and policy. Building on work suggesting how agencies can
      support such knowledge translation (KT), this paper discusses an online survey to
      assess KT training needs of researchers and research users as part of a Canadian
      provincial capacity-building effort. METHODS: The survey comprised 24 multiple
      choice and open-ended questions including demographics, interest in learning KT
      skills, likelihood of participating in training, and barriers and facilitators to
      doing KT at work. More than 1,200 people completed the survey. The high number of
      responses is attributed to an engagement strategy involving partner organizations
      (health authorities, research institutes, universities) in survey development and
      distribution. SPSS was used to analyze quantitative results according to
      respondents' primary role, geographic region, and work setting. Qualitative
      results were analyzed in NVivo. RESULTS: Over 85 percent of respondents are
      interested in learning more about the top KT skills identified. Research
      producers have higher interest in disseminating research results; research users
      are more interested in the application of research results. About one-half of
      respondents require beginner-level training in KT skills; one-quarter need
      advanced training. Time and cost constraints are the biggest barriers to
      participating in KT training. More than one-half of respondents have no financial
      support for travel and almost one-half lack support for registration fees. Time
      is the biggest challenge to integrating KT into work. CONCLUSIONS: Online surveys
      are useful for determining knowledge translation training needs of researchers,
      research users and ultimately organizations. In this case, findings suggest the
      importance of considering all aspects of KT in training opportunities, while
      taking into account different stakeholder interests. Funders can play a role in
      developing new training opportunities as part of a broad effort, with partners,
      to build capacity for the use of health research evidence. Survey results would
      ideally be complemented with an objective needs assessment based on core
      competencies, and should be acted on in a way that acknowledges the complexity of
      knowledge translation in healthcare, existing training activities, and the
      expertise stakeholders already have but may not refer to as knowledge
      translation.

PMID- 24906231
TI  - Association between cancer and Alzheimer's disease: systematic review and meta
      analysis.
AB  - This study examined the association between cancer and Alzheimer's disease (AD)
      by a quantitative meta-analysis of cohort studies. Studies were identified by
      searching PubMed database through 1966 to December 2013 using the terms
      "Alzheimer's disease", "neoplasm", and "cancer". Six studies met the inclusion
      criteria in the overall meta-analysis. We pooled effect sizes using fixed-effects
      and random-effects models. Furthermore, we also tested for heterogeneity and
      publication bias. The results suggested that individuals diagnosed with AD had a
      decreased risk for incident cancer by 42% (95% CI, 0.40-0.86; p < 0.05), and
      patients with a history of cancer had a 37% decreased risk of AD (RR = 0.63; 95%
      CI, 0.56-0.72; p = 0.495). The Egger's test for publication bias (p = 0.280)
      showed no significant evidence for bias in the data from studies on AD and cancer
      risk. In summary, our meta-analysis demonstrated an inverse association between
      cancer and AD. 

PMID- 24906230
TI  - Identification of a New Delhi metallo-beta-lactamase-4 (NDM-4)-producing
      Escherichia coli in Italy.
AB  - BACKGROUND: During June-July 2012, six imipenem-resistant Escherichia coli
      isolates were isolated from two patients hospitalized in a ward of one large
      tertiary-care hospital in Genoa, Italy. Genetic features associated with blaNDM-4
      gene were investigated. RESULTS: The isolates exhibited the same PFGE profile and
      a multidrug-resistant (MDR) phenotype to aminoglycosides, fluoroquinolones, and
      beta-lactams. The strains produced the NDM-4 carbapenemase and the blaNDM-4 gene
      was part of the variable region of a class 1 integron. MLST analysis revealed
      that all isolates belonged to sequence type 405 (ST405). CONCLUSIONS: This is the
      first report on the emergence of an MDR strain of E.coli producing the NDM-4 MBL
      in Italy.

PMID- 24906232
TI  - Comparative evolutionary analysis of cell cycle proteins networks in fission and
      budding yeast.
AB  - Fission yeast and budding yeast are the two distantly related species with common
      ancestors. Various studies have shown significant differences in metabolic
      networks and regulatory networks. Cell cycle regulatory proteins in both species
      have differences in structural as well as in functional organization. Orthologous
      proteins in cell cycle regulatory protein networks seem to play contemporary role
      in both species during the evolution but little is known about non-orthologous
      proteins. Here, we used system biology approach to compare topological parameters
      of orthologous and non-orthologous proteins to find their contributions during
      the evolution to make an efficient cell cycle regulation. Observed results have
      shown a significant role of non-orthologous proteins in fission yeast in
      maintaining the efficiency of cell cycle regulation with less number of proteins
      as compared to budding yeast. 

PMID- 24906233
TI  - Complications of laparoscopic versus open bariatric surgical interventions in
      obesity management.
AB  - With the epidemic of obesity fast spreading its grasp throughout the world, the
      medical professionals of diverse facilities need to be called on for better
      management to prevent its further progression. In particular, the
      gastroenterologists have a major role to play in all aspects of obese patient
      care. They should be able to recognize and treat obesity and associated disorders
      through the understanding and assessment of the various benefits and risks linked
      with a particular type of obesity treatment option. While treating these
      problems, a better understanding of the physiologic and anatomic alterations that
      might be associated with the treatment procedure and the weight loss-linked
      problems in association with the method of surgical intervention need to be
      weighed. Morbid obesity has been efficaciously treated by bariatric surgery
      promoting weight loss considerably and reducing the obesity-associated risks such
      as certain cancers, diabetes, cardiovascular disease, and all-cause mortality.
      Bariatric surgery has been performed traditionally through open method or, the
      more recent and popular form, laparoscopically that involves only a small
      incision in the abdomen. The laparoscopic bariatric surgery has become the
      surgical method of choice since its introduction in 1993 and has immediately
      crossed open surgery in terms of popularity. Drastic numbers came out when the
      two methods were compared for their applicability during a 3-year period in the
      United States. Only 6,000 reported open gastric bypass surgeries were recorded,
      but the number soared to nearly 16,000 for laparoscopic gastric bypass surgeries.
      The laparoscopic method has been found to be associated with much reduced
      complications and hospital stay along with lower cases of mortality as suggested
      by small randomized controlled trials and observational studies. However, these
      facts need to be reassessed through large-sized controlled trials and population
      based studies. In addition, the previously ignored complications associated with
      laparoscopic methods should be studied in detail. Since the cases of obesity have
      been ever increasing and bariatric surgery is also gaining in popularity, it is
      important that the safest procedure should be identified. The main objective of
      this review was to compare the benefits and risks associated with open versus
      laparoscopic mode of bariatric surgery with a greater focus on the laparoscopic
      method. Although there are few reviews that have compared the two methods, none
      have focused on the complications of the two approaches. All these aspects have
      been dealt in detail here. 

PMID- 24906235
TI  - Adiponectin induces breast cancer cell migration and growth factor expression.
AB  - Adiponectin, the hormone produced and secreted by adipocytes, has been shown to
      promote migration of the epithelial cells and angiogenesis in these cells. We
      sought to determine if adiponectin could induce the cellular migration and growth
      factor expression in breast cancer cells grown in vitro. The breast cancer cell
      lines MDA-MB-436 and MFM-223 (estrogen-independent) were treated with adiponectin
      for different time periods. Supernatants of the cell cultures were obtained by
      centrifugation and were assayed for growth factor expression by the enzyme-linked
      immunosorbent assay (ELISA). Becton-Dickinson-Falcon Transwell systems were used
      to assay adiponectin-induced migration. Adiponectin significantly induced the
      expression of various growth factors, including vascular endothelial growth
      factor, transforming growth factor-beta1, and basic fibroblast growth factor in
      MDA-MB-436 and MFM-223 cells. Adiponectin also enhanced the migration of breast
      cancer cells which were inhibited about 50-70 % by the inhibitors of mitogen
      activated protein kinase and phosphatidylinositol 3-kinase (PI3K). Adiponectin
      treatment of the cancer cell induced an increased expression of different growth
      factors and migration of the cells. These effects are likely to contribute to the
      progression of breast cancer, implying that change in adiponectin levels
      associated with obesity may be considered as a high risk factor in breast cancer
      patients.

PMID- 24906234
TI  - Correlation between brachial-ankle pulse wave velocity, carotid artery intima
      media thickness, ankle-brachial index, and the severity of coronary lesions.
AB  - Coronary angiography is the gold standard for the diagnosis of coronary artery
      disease. Coronary artery Gensini scoring systems measure both the extent and the
      degree of stenosis of coronary artery and therefore, give clinicians a more
      accurate, objective, and comprehensive assessment of the severity of coronary
      artery disease. Using Gensini scoring systems in combination with statistical
      analysis, we found that five variables, namely, Brachial-ankle pulse wave
      velocity (PWV), ankle-brachial index (ABI), carotid artery intima-media thickness
      (IMT), blood sugar, and high density lipoprotein cholesterol (HDL-C), were all
      significantly different among groups of patients with different Gensini scores.
      All five variables can be used for early screening and assessment of coronary
      artery disease as independent prognostic factors for the morbidity and mortality
      from cardiovascular conditions. With the progression of coronary artery disease,
      the levels of PWV, IMT, and blood glucose are gradually increasing whereas the
      levels of ABI and HDL-C are gradually decreasing. These changes can be treated as
      warning signs and can also be helpful in evaluating the severity of coronary
      artery diseases. It is highly recommended to perform these five non-invasive
      tests as early as possible in order to identify high-risk patients at their
      subclinical stages. This would allow timely intervention and thereby lead to
      reduced morbidity and mortality from cardiovascular diseases. 

PMID- 24906236
TI  - Knockdown of Burton's tyrosine kinase confers potent protection against sepsis
      induced acute lung injury.
AB  - Sepsis is a common and critical complication in surgical patients that often
      leads to multiple organ failure syndrome (MOFS), including acute lung injury
      (ALI) and acute respiratory distress syndrome (ARDS). Despite intensive
      supportive care and treatment modalities, the mortality of these patients remains
      high. In this study, we investigated the role of Burton's tyrosine kinase (BTK),
      a member of the Btk/Tec family of cytoplasmic tyrosine kinases, in the
      pathogenesis of sepsis, and evaluated the protective effect of in vivo Btk RNA
      interference in a mouse model of cecal ligation and puncture (CLP)-induced
      sepsis. After intratracheal injection of Btk siRNA, the mice were then subjected
      to CLP to induce sepsis. The results demonstrated that this approach conferred
      potent protection against sepsis-induced ALI, as evidenced by a significant
      reduction in pathological scores, epithelial cell apoptosis, pulmonary edema,
      vascular permeability, and the expression of inflammatory cytokines and
      neutrophil infiltration in the lung tissues of septic mice. In addition, RNA
      interference of Btk significantly suppressed p-38 and iNOS signaling pathways in
      transduced alveolar macrophages in vitro. These results identify a novel role for
      BTK in lethal sepsis and provide a potential new therapeutic approach to sepsis
      and ALI. 

PMID- 24906237
TI  - Role of the embryonic protein SOX2 in cholangiocarcinoma.
AB  - SOX2 overexpression correlates with aggressive behavior and poor overall survival
      in cholangiocarcinoma (CCA). However, the cellular functions and precise role of
      SOX2 in CCA have not been elucidated. Here, we inserted SOX2 coding sequence to
      establish a CAA cell line which stably overexpressed SOX2. In vitro experiments
      showed that overexpression of SOX2 in cells was associated with increased cell
      proliferation, suppressed cell apoptosis, as well as enhanced cell migration and
      invasion. Our findings may lead to a better understanding of the biological
      effect of SOX2 and provide mechanistic insights for developing potential
      therapeutic strategies for CCA treatment. 

PMID- 24906238
TI  - The association of 9p21-3 locus with coronary atherosclerosis: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Studies suggest that the 9p21-3 locus may influence susceptibility to
      myocardial infarction. We performed a systematic review and meta-analysis to
      assess whether this locus is associated with severity of coronary atherosclerosis
      and adverse clinical outcomes in those with known coronary disease. METHODS:
      Multiple electronic databases were searched from inception through August 2012.
      Studies examining 9p21-3 genotype in patients with known coronary artery disease
      were included. We extracted the association of the 9p21-3 locus with measures of
      severity of coronary atherosclerosis [number of diseased vessels, Gensini Score,
      Duke CAD Prognostic Index (DPI)], angiographic outcomes [change in minimum lumen
      diameter (?MLD) and number of new lesions at follow-up], and key clinical
      outcomes (all-cause mortality, recurrent myocardial infarction and the need for
      coronary revascularization). Relative risks (RR) and weighted mean difference
      (WMD) were pooled using the random effects models. RESULTS: 23 cohorts enrolling
      16,860 participants were analyzed. There was no significant difference between HR
      and LR genotypes in terms of all-cause mortality, recurrent myocardial infarction
      or the frequency of coronary revascularization. HR genotype was associated with
      increased risk of triple vessel disease (RR = 1.34; 95% CI 1.08-1.65; P = 0.01)
      and increased baseline Gensini Score (WMD = 5.30; 95% CI 0.66-9.93; P = 0.03).
      However there was no association with DPI (WMD = 4.00; 95% CI 2.94-10.94; P =
      0.26). HR genotype did not predict ?MLD or number of new lesions at follow-up.
      CONCLUSIONS: Patients of coronary atherosclerosis who carry the high risk
      genotype of the 9p21-3 allele may be more likely to have multi-vessel CAD.
      However the effect of this allele on CAD progression and disease specific
      clinical outcomes are not observed possibly due to diminishing genetic risk
      following dietary modification and therapy.

PMID- 24906239
TI  - Why carers use adult day respite: a mixed method case study.
AB  - BACKGROUND: We need to improve our understanding of the complex interactions
      between family carers' emotional relationships with care-recipients and carers
      use of support services. This study assessed carer's expectations and perceptions
      of adult day respite services and their commitment to using services. METHODS: A
      mixed-method case study approach was used with psychological contract providing a
      conceptual framework. Data collection was situated within an organisational case
      study, and the total population of carers from the organisation's day respite
      service were approached. Fifty respondents provided quantitative and qualitative
      data through an interview survey. The conceptual framework was expanded to
      include Maslow's hierarchy of needs during analysis. RESULTS: Carers prioritised
      benefits for and experiences of care-recipients when making day respite
      decisions. Respondents had high levels of trust in the service and perceived that
      the major benefits for care-recipients were around social interaction and
      meaningful activity with resultant improved well-being. Carers wanted day respite
      experiences to include all levels of Maslow's hierarchy of needs from the
      provision of physiological care and safety through to the higher levels of
      belongingness, love and esteem. CONCLUSION: The study suggests carers need to
      trust that care-recipients will have quality experiences at day respite. This
      study was intended as a preliminary stage for further research and while not
      generalizable it does highlight key considerations in carers' use of day respite
      services.

PMID- 24906240
TI  - [Current care strategies for Duchenne muscular dystrophy].
AB  - BACKGROUND: The medical care of patients with Duchenne muscular dystrophy (DMD)
      is an interdisciplinary and multifaceted task. The vast majority of those
      affected show a nearly constant course which is reflected in a corresponding
      stage-oriented treatment concept. Although there is still no causal therapy
      available for DMD, the course and in particular the quality of life of patients
      can be decisively improved by established medical practices. THERAPEUTIC
      STRATEGIES: The orthopedic problems of DMD patients include contractures of the
      upper and lower extremities as well as sitting instability due to progressive
      scoliosis with pelvic imbalance. The orthopedic treatment incorporates
      conservative measures, such as physiotherapy, provision of orthotic devices and
      wheelchairs as well as surgery to resolve contractures of the lower extremities
      and surgical stabilization of the spine. Furthermore, in these patients
      orthopedic surgeons and trauma surgeons are confronted with the treatment and
      prophylaxis of fractures induced by osteoporosis. An early onset of
      glucocorticoid therapy markedly delays the loss of motor abilities. TREATMENT
      ASPECTS: An important aspect in the care of DMD patients is the timely
      prophylaxis and treatment of respiratory insufficiency with regular sessions of
      breathing therapy, learning breathing and coughing techniques and the
      sufficiently early start of non-invasive mechanically assisted ventilation. Of
      similar relevance are also the early recognition and cardioprotective treatment
      of cardiomyopathy. CONCLUSION: The orthopedic surgeon accompanies the patient and
      family through all stages of the disease and must be appropriately informed on
      current management and treatment strategies even outside the limits of the
      personal field of specialization.

PMID- 24906241
TI  - [Molecular genetic analysis and clinical aspects of patients with hereditary
      hemochromatosis].
AB  - BACKGROUND: The purpose of the study was to perform a molecular genetic analysis
      and to document clinical aspects in patients with hereditary hemochromatosis.
      PATIENTS AND METHODS: The study included 33 outpatients (23 males average age
      50.6 years and 10 females average age 60.6 years) with a disorder of iron
      metabolism (transferrin saturation > 75 %) as confirmation of hemochromatosis who
      were subjected to molecular genetic and clinical analyses. RESULTS: A homozygous
      mutation of the hemochromatosis (HFE) gene (C282YY) was detected in 63.6 %, a
      compound heterozygous mutation (C282Y/H63D) in 30.3% and no mutation of the HFE
      gene was detected in 6.1 %. The following organ manifestations could be
      objectified: arthralgia (78.8 %), liver disease (39.9 %), skin hyperpigmentation
      (30.3 %), osteoporosis (24.2 %), diabetes mellitus (24.2 %) and cardiomyopathy
      (12.1 %). Comparison between patients with heterozygous and homozygous
      hemochromatosis revealed the following differences: compound heterozygote
      patients presented less frequently with osteoarthritis of the metacarpophalangeal
      (MCP) joints and hands (85.7 %/71.4 % homozygotes vs. 60 %/60 % heterozygotes).
      Osteoarthritis of the shoulder joints and osteoporosis as well as hypothyroidism
      were more frequent in compound heterozygote patients, whereas osteoarthritis of
      the knee and hip joints as well as liver disease were more common in homozygote
      patients. No differences between both groups were seen with respect to the
      clinical manifestations of cardiomyopathy and diabetes mellitus. CONCLUSION:
      Prevalent causes of death in hereditary hemochromatosis are heart failure, liver
      disease (cirrhosis and hepatocellular carcinoma) and portal hypertension.
      Therefore, an early diagnosis, adequate therapy and genetic screening of family
      members are of great importance. Medicinal treatment will only effectively
      prevent deleterious organ involvement and subsequent complications if initiated
      at an early stage. Furthermore, an overview of the current data is given.

PMID- 24906242
TI  - Cryptogamic community structure as a bioindicator of soil condition along a
      pollution gradient.
AB  - This study aims to determine changes in the structure of cryptogamic vegetation
      of poor psammophilous grassland along a pollution gradient near a zinc smelter to
      evaluate the potential of species assemblages as bioindicators of soil condition.
      Lichens and bryophytes were examined in study plots along six transects in four
      distance zones, and the physicochemical properties of corresponding soil samples
      were analysed. Four different responses of species to substrate contamination
      were identified, with a distinct group of species resistant to and favoured by
      metal contamination. Although species richness decreases as one approaches the
      smelter, the gradual replacement of certain sensitive species by resistant ones
      was observed along the pollution gradient. The results enabled us to develop a
      useful tool to diagnose strongly polluted sites. Two different cryptogamic
      assemblages of well-recognised key species characteristic for strongly polluted
      and lightly polluted sites were distinguished. We conclude that cryptogamic
      community structure clearly corresponds to the degree of soil contamination, thus
      demonstrating high bioindicative value. The study confirmed the high relevance of
      the community approach in metal pollution biomonitoring. 

PMID- 24906243
TI  - Association of the myosin binding protein C3 mutation (MYBPC3 R820W) with cardiac
      death in a survey of 236 Ragdoll cats.
AB  - OBJECTIVES: A mutation identified in the myosin binding protein C3 gene (MYBPC3
      R820W) has been associated with hypertrophic cardiomyopathy (HCM) in Ragdoll
      cats. Ragdolls with HCM are reported to have a poor prognosis and homozygous cats
      seem particularly likely to develop severe HCM, although the outcome in Ragdolls
      tested for the MYBPC3 mutation has not been reported. We aimed to determine the
      influence of genotype on survival in Ragdoll cats using a questionnaire, and
      hypothesized that homozygous Ragdolls had shorter lifespans and were more likely
      to suffer cardiac death than heterozygous or wild-type (WT) cats. ANIMALS: 251
      client owned Ragdoll cats. METHODS: A questionnaire for breeders/owners of MYBPC3
      genotyped Ragdolls included items related to genotype, age, sex, current status
      (alive/dead), and date and circumstances of death. Death was categorized as
      cardiac or non-cardiac. Survival was analyzed using Kaplan-Meier curves and log
      rank tests. RESULTS: Completed questionnaires were received for 236 cats (156 WT,
      68 heterozygous, 12 homozygous). Median survival time for homozygous cats was
      5.65 years (95%CI 0.4-10.9 years) compared to heterozygous (>16.7 years) or WT
      (>15.2 years). Homozygous cats were more likely to die from cardiac death (p =
      0.004 vs. WT; p = 0.003 vs. heterozygous) and had significantly shorter time to
      cardiac death (vs. WT p < 0.001; vs. heterozygous p < 0.001). CONCLUSIONS:
      Ragdoll cats homozygous for the MYBPC3 R820W mutation have a shorter survival
      time than WT or heterozygous cats. This suggests a mode of inheritance that
      follows an incomplete dominance pattern.

PMID- 24906244
TI  - Expectation of volunteers towards the vaccine efficacy of the prime-boost HIV
      vaccine phase III trial during unblinding.
AB  - A Phase III community-based HIV vaccine trial using the ALVAC-HIV and AIDSVAX B/E
      prime-boost regimen (RV144) showed a modest vaccine efficacy of 31.2% against HIV
      acquisition. Participant's understanding of the trial is a key element of its
      success. This study aimed to understand participant's expectation and response to
      the overall results of the trial as well after unblinding. Using an open-ended
      questionnaire, data were collected from 400 participants who came for the
      unblinding visit. Fifty-three percent received the vaccine and 47% were placebo
      recipients. The median age was 30 years (range: 22-37). The observed vaccine
      efficacy of 31.2% was lower than expected by 67.75% of participants compared to
      higher than expected (by 6%), as expected (by 11.25%), and those with no
      expectation (15%). A majority of participants (71.5%) were happy and proud, and
      indicated that it was a good result. The rest were sad or disappointed (22.75%)
      or acquiescent (5.75%). After unblinding, 67.92% of the vaccine recipients had a
      positive response and 32.08% were acquiescent. Among placebo recipients, 85.11%
      were acquiescent and 10.11% indicated that being assigned to the vaccine group
      would have been better even though vaccine efficacy was only 31.2%. Despite the
      modest vaccine efficacy, a majority of study participants acknowledged the value
      of the trial and hoped that information from RV144 could be used for future
      vaccine development.

PMID- 24906245
TI  - Minimally-invasive posterior lumbar stabilization for degenerative low back pain
      and sciatica. A review.
AB  - The most diffused surgical techniques for stabilization of the painful
      degenerated and instable lumbar spine, represented by transpedicular screws and
      rods instrumentation with or without interbody cages or disk replacements,
      require widely open and/or difficult and poorly anatomical accesses. However,
      such surgical techniques and approaches, although still considered "standard of
      care", are burdened by high costs, long recovery times and several potential
      complications. Hence the effort to open new minimally-invasive surgical
      approaches to eliminate painful abnormal motion. The surgical and radiological
      communities are exploring, since more than a decade, alternative, minimally
      invasive or even percutaneous techniques to fuse and lock an instable lumbar
      segment. Another promising line of research is represented by the so-called
      dynamic stabilization (non-fusion or motion preservation back surgery), which
      aims to provide stabilization to the lumbar spinal units (SUs), while maintaining
      their mobility and function. Risk of potential complications of traditional
      fusion methods (infection, CSF leaks, harvest site pain, instrumentation failure)
      are reduced, particularly transitional disease (i.e., the biomechanical stresses
      imposed on the adjacent segments, resulting in delayed degenerative changes in
      adjacent facet joints and discs). Dynamic stabilization modifies the distribution
      of loads within the SU, moving them away from sensitive (painful) areas of the
      SU. Basic biomechanics of the SU will be discussed, to clarify the mode of action
      of the different posterior stabilization devices. Most devices are minimally
      invasive or percutaneous, thus accessible to radiologists' interventional
      practice. Devices will be described, together with indications for patient
      selection, surgical approaches and possible complications. 

PMID- 24906246
TI  - Preliminary study on evaluation of the pancreatic tail observable limit of
      transabdominal ultrasonography using a position sensor and CT-fusion image.
AB  - BACKGROUND AND AIM: Transabdominal ultrasonography (US) is commonly used for the
      initial screening of bilio-pancreatic diseases in Asian countries due to its
      widespread availability, the non-invasiveness and the cost-effectiveness.
      However, it is considered that US has limits to observe the area, namely the
      blind area. The observation of the pancreatic tail is particularly difficult. The
      goal of this study was to examine the pancreatic tail region that cannot be
      visualized on transverse scanning of the upper abdomen using US with spatial
      positional information and factors related to visualization, and observation of
      the tail from the splenic hilum. METHODS: Thirty-nine patients with
      pancreatic/biliary tract disease underwent CT and US with GPS-like technology and
      fusion imaging for measurement of the real pancreatic length and the
      predicted/real unobservable (PU and RU) length of the pancreatic tail. RU from US
      on transverse scanning and the real pancreatic length were used to determine the
      unobservable area (UA: RU/the real pancreatic length). Relationships of RU with
      physical and hematological variables that might influence visualization of the
      pancreatic tail were investigated. RESULTS: The real pancreatic length was 160.9
      +/- 16.4mm, RU was 41.0 +/- 17.8mm, and UA was 25.3 +/- 10.4%. RU was correlated
      with BMI (R=0.446, P=0.004) and waist circumferences (R=0.354, P=0.027), and
      strongly correlated with PU (R=0.788, P<0.001). The pancreatic tail was visible
      from the splenic hilum in 22 (56%) subjects and was completely identified in 13
      (33%) subjects. CONCLUSIONS: Combined GPS-like technology with fusion imaging was
      useful for the objective estimation of the pancreatic blind area.

PMID- 24906248
TI  - The clinical relevance of microbiology specimens in head and neck space
      infections of odontogenic origin.
AB  - It is common surgical practice to take a specimen for microbial culture and
      sensitivity when incising and draining infections of odontogenic origin in the
      head and neck. We aimed to find out if routine testing has any therapeutic value.
      We retrospectively studied 90 patients (57 male and 33 female) admitted to
      Northampton General Hospital for treatment of odontogenic infections, and
      reviewed admission details, antimicrobial treatment, microbiological findings and
      their sensitivity or resistance, and complications. Specimens were sent from 72
      (80%) patients of which 61 (85%) were infected. The most commonly isolated
      organism was Streptococcus viridans. Interim reports were published after a mean
      of 3 days (range 1-4), and 94% of patients were discharged within a mean of 2
      days (range 0-9) postoperatively. Almost 95% of patients were discharged before
      results were available, and there were no reported complications. We therefore
      suggest that microbial culture has little therapeutic value in the management of
      these patients. With culture and sensitivity tests costing L25 - L30, omission of
      this practice in the case of uncomplicated (single tissue space) odontogenic
      infections could save resources in the National Health Service without affecting
      the care of patients.

PMID- 24906247
TI  - Similarity of patient characteristics and outcomes in consecutive data collection
      on stroke admissions over one month compared to longer periods.
AB  - BACKGROUND: The usefulness of time-limited consecutive data collection compared
      to continuous consecutive data collection in conditions which show seasonal
      variations is unclear. The objective of this study is to assess whether one month
      of admission data can be representative of data collected over two years in the
      same hospitals. METHODS: We compared the baseline characteristics and discharge
      outcomes of stroke patients admitted in the first month (October 2009) of the
      Anglia Stroke Clinical Network Evaluation Study (ASCNES) with the routinely
      collected data over 2 years between September 2008 and April 2011 from the same 8
      hospital trusts in the Anglia Stroke & Heart Clinical Network (AS&HCN) as well as
      seasonal cohorts from the same period. RESULTS: We included a total of 8715
      stroke patients (October 2009 cohort of ASCNES (n = 308), full AS&HCN cohort (n =
      8407 excluding October 2009)) as well as cohorts from different seasons. All
      cohorts had a similar median age. No significant differences were observed for
      pre-stroke residence, pre-stroke modified Rankin, weekend vs. weekday admission,
      time of admission, patients with atrial fibrillation, type of stroke, admission
      systolic blood pressure, use of thrombolysis (rTPA), in-patient mortality and
      discharge destination. There were statistically significant differences between
      cohorts with regard to Oxfordshire Community Stroke Project Classification.
      CONCLUSIONS: Stroke patients admitted in one month had largely indistinguishable
      characteristics and discharge outcomes to those admitted to the same trusts in
      three separate seasons and also over two years in this cohort.

PMID- 24906249
TI  - Microbiological examination and antibiotic sensitivity of infections in the head
      and neck. Has anything changed?
AB  - Because of the growing concern about antibiotic resistance, we aimed to
      investigate whether the microbiological picture and antibiotic sensitivity of
      infections in the head and neck have changed in the last 30-40 years. We
      retrospectively studied 150 patients admitted for inpatient treatment of
      infections in the head and neck, and searched published reports from the last 30 
      40 years for comparison. There were 85 male and 65 female patients (mean age 39
      years, range 1-95). Most infections originated from the teeth (n = 111) and skin
      (n = 16), and the submandibular (69%) and buccal (67%) spaces were involved most
      often. Multiple spaces were involved in 94 patients. Swabs were taken for culture
      and sensitivity in 102 cases, and microorganisms were isolated in 91 (89%), of
      which 67 (74%) were aerobic infections and 24 (26%) were anaerobic. Bacteria were
      isolated in 87 (96%) cultures of which 60 (69%) were Gram-positive. Gram-positive
      cocci were isolated in 62% of cultures. The most common bacteria isolated were
      streptococci. Seventy percent of the bacteria were sensitive to amoxicillin and
      84% to amoxicillin and metronidazole; 14% (Staphylococcus aureus from infections
      of the skin) were resistant to penicillin. A comparison of our results with those
      found in previous reports shows no significant change in the microbiological
      picture and antibiotic sensitivity of odontogenic infections in the head and neck
      over the last 30 - 40 years. Amoxicillin still treats these infections
      effectively. 

PMID- 24906250
TI  - Modification of intraoral vertical ramus osteotomy.

PMID- 24906251
TI  - Re: Why should I follow up my patients with oral lichen planus and licheniod
      reactions? Greaney L, Kerawala C, Cascarini L, Godden D, Coombes D. Br J Oral
      Maxillofac Surg 2014; 52: 291-3.

PMID- 24906252
TI  - Pharmacokinetic-pharmacodynamic relationships of macitentan, a new endothelin
      receptor antagonist, after multiple dosing in healthy Korean subjects.
AB  - BACKGROUND AND OBJECTIVES: Macitentan is a novel dual endothelin (ET)-1 receptor
      antagonist to be used in patients with pulmonary arterial hypertension. This
      study aimed to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of
      macitentan after administration of multiple doses to healthy Korean male
      subjects. METHODS: A randomized, double-blind, placebo-controlled, multiple
      ascending dose study was performed in 30 healthy male subjects receiving oral
      macitentan (3, 10, or 30 mg) or placebo once daily for 10 days. Plasma
      concentrations of macitentan, its active metabolite ACT-13277, and ET-1 were
      evaluated. Safety and tolerability measurements were conducted throughout the
      study. RESULTS: The concentration-time profile of macitentan was characterized by
      slow absorption (median time to maximum plasma concentration [t(max)] 9-10 h) and
      slow elimination (mean elimination half-life [t 1/2] 11-15 h). After repeated
      doses of 3, 10, and 30 mg of macitentan over the course of 10 days, the peak
      concentration (C(max)) increased as the dose increased and the area under the
      plasma concentration-time curve during the dosing interval (AUC(tau)) increased
      in a dose-proportional manner. Plasma concentrations showed approximately 1.5- to
      1.9-fold accumulation on day 10 compared with day 1. ACT-132577 showed higher
      levels of exposure than macitentan, its mean half-life was 46-48 h, and it
      accumulated 7- to 12-fold. Macitentan increased plasma ET-1 concentrations at all
      doses tested and was well tolerated and elicited no serious adverse events.
      CONCLUSION: Multiple oral doses of 3, 10, and 30 mg of macitentan were well
      tolerated in healthy Korean subjects, and its pharmacokinetics correlated
      positively with ET-1 concentrations.

PMID- 24906254
TI  - Effectiveness of enzyme replacement therapy in adults with late-onset Pompe
      disease: results from the NCS-LSD cohort study.
AB  - OBJECTIVES: To determine the effectiveness of enzyme replacement therapy (ERT)
      for adults with late-onset Pompe disease. DESIGN: A longitudinal cohort study
      including prospective and retrospective clinical outcome data. Age- and gender
      adjusted treatment effects were estimated using generalised linear mixed models.
      Treated patients contributed data before and during treatment. Untreated patients
      contributed natural history data. PARTICIPANTS: Consenting adults (N = 62) with a
      diagnosis of late-onset Pompe disease who attended a specialist treatment centre
      in England. This cohort represented 83 % of all patients in the UK with a
      confirmed diagnosis of this rare condition. At study entry, all but three
      patients were receiving ERT (range of treatment duration, 0 to 3.1 years).
      OUTCOME MEASURES: Percent predicted forced vital capacity (%FVC); ventilation
      dependency; mobility; 6 min walk test (6MWT); muscle strength and body mass index
      (BMI). RESULTS: An association was found between time on ERT and significant
      increases in the distance walked in the 6MWT (p < 0.001) and muscle strength
      scores (p < 0.001). Improvements in both these measures were seen over the first
      2 years of treatment with ERT. No statistically significant relationship was
      found between time on ERT and respiratory function or in BMI. CONCLUSIONS: These
      data provide some further evidence of the effectiveness of ERT in adults with
      late-onset Pompe disease. SYNOPSIS: The results of this longitudinal cohort study
      of 62 adults with late-onset Pompe disease, provide further evidence on the
      effectiveness of ERT in this rare condition.

PMID- 24906255
TI  - Primary renal aspergillosis and xanthogranulomatous pyelonephritis in an immuno
      competent toddler.
AB  - Aspergillosis is primarily a pulmonary disease so that renal aspergillosis is
      usually secondary to hematogenous spread from lungs. Primary renal aspergillosis,
      though a rare entity, is still seen in immuno-compromised individuals. Renal
      aspergillosis may lead to formation of focal abscesses, fungal bezoars and may
      cause ureteric obstruction. Treatment involves stabilization of patient and
      removal of fungal bezoars along with administration of anti-fungal agents. This
      report describes the case of localized primary renal aspergillosis with fungal
      bezoar formation in 2 years old immuno-competent child who presented in sepsis
      and acute renal failure and was successfully managed by nephroscopic removal of
      fungal bezoar and intravenous voriconazole. The other kidney required nephrectomy
      for xanthogranulomatous pyelonephritis. 

PMID- 24906253
TI  - Parkinsonism and inborn errors of metabolism.
AB  - Parkinsonism is a frequent neurological syndrome in adulthood but is very rare in
      childhood. Early forms of Parkinsonism have many distinctive features as compared
      to Parkinsonism in adults. In fact, rather than Parkinsonism, the general concept
      "hypokinetic-rigid syndrome" (HRS) is more accurate in children. In general, the
      terms "dystonia-parkinsonism", "parkinsonism-plus", or "parkinsonism-like" are
      preferred to designate these forms of paediatric HRS. Inborn errors of metabolism
      (IEM) constitute an important group amongst the genetic causes of Parkinsonism at
      any age. The main IEM causing Parkinsonism are metal-storage diseases,
      neurotransmitter defects, lysosomal storage disorders and energy metabolism
      defects. IEM should not be neglected as many of them represent treatable causes
      of Parkinsonism. Here we review IEMs causing this neurological syndrome and
      propose diagnostic approaches depending on the age of onset and the associated
      clinical and neuroimaging features. 

PMID- 24906256
TI  - Familial Fahr's disease presenting with Parkinsonism in a young male.
AB  - Fahr's syndrome is a rare idiopathic neurodegenerative disorder which can present
      with wide spectrum of symptoms. It is characterized by bilateral symmetrical
      dystrophic intracranial calcification. It most commonly involves basal ganglia. A
      30 years old male patient presented with progressive speech slurring and tremors
      of the right upper limb for last five years. His brain imaging studies revealed
      findings of extensive dystrophic calcification. He had an elder sister who had
      progressive limb weakness, tremors and speech slurring. Her brain imaging studies
      also showed same findings. On the basis of family history, neuroimaging findings
      and laboratory investigations, patient was diagnosed with the case of familial
      Fahr's disease. Fahr's disease should be considered as an important differential
      diagnosis in cases of Parkinsonism refractory to the treatment. 

PMID- 24906257
TI  - Early recovery in post Varicella transverse myelitis.
AB  - A 7 years old boy presenting with acute flaccid paralysis after Varicella zoster
      infection was diagnosed as having acute transverse myelitis on MRI. He recovered
      fully after treatment with intravenous corticosteroids and acyclovir. The
      occurrence of this condition during or following Varicella infection is uncommon.
      There are previously very few reported cases of post-Varicella acute transverse
      myelitis in which recovery started after 3 months of treatment. In this case
      complete recovery occurred in 2 weeks of treatment. This report emphasizes the
      need for Varicella zoster vaccine to prevent not only acute Varicella, but also
      its rare postinfectious neurologic sequelae. 

PMID- 24906258
TI  - Right atrial invasion by metastatic esophageal adenocarcinoma with direct
      connection to liver.
AB  - Common causes of right sided intra-cardiac atrial masses include primary cardiac
      tumors (atrial myxoma), atrial thrombus, tumor thrombus with hepatocellular or
      other thoracoabdominal cancers and metastatic lesions. Invasion of atria by
      gastrointestinal tumors is rare and that with esophageal ones seldom observed.
      Esophageal cancers rather present with dysphagia, odynophagia or systemic
      symptoms. Due to the lack of a serosal layer, esophageal tumors usually spread
      early in their course. Typical sites of spread include liver, gut, mediastinum,
      lungs and draining lymph nodes. We report a case of metastatic esophageal
      adenocarcinoma presenting with direct extension of metastatic tumor thrombus from
      liver to right atrium via inferior vena cava. 

PMID- 24906259
TI  - Iridocorneal endothelial syndrome.
AB  - A 19 years boy with a 2 years history of reduced and fluctuating vision along
      with change in pupillary shape and iris colour in his left eye presented to the
      glaucoma clinic. Ocular examination revealed distinct unilateral stretch holes,
      iris architecture changes and localized iris atrophy. Intraocular pressure was 16
      mmHg in the right and 36 mmHg in the left eye. Gonioscopy of the left angle
      revealed broad based peripheral anterior synechiae at approximately 2 O'clock to
      10 O'clock hours. The optic disc of the left eye had a vertical cup of 0.9 which
      manifest as superior and inferior arcuate scotoma. Specular microscopy showed
      unilateral abnormal endothelium with irregular cells of variable shape and size.
      To our knowledge, this is only the second reported case of iridocorneal
      endothelial syndrome in a male teenager. 

PMID- 24906260
TI  - Spontaneous closure of macular hole.
AB  - We report a case of spontaneous closure of stage-II macular hole. A 66 years old
      lady presented with decreased vision in her left eye for the last 3 months. Her
      vision was 6/18 in right eye and finger counting at 3 feet in left eye. Optical
      coherence tomography showed stage-II macular hole in left eye. There was
      attachment of vitreous at the edge of the hole. Minimal hole diameter was 119 MU.
      Macular hole surgery was planned. During follow-up, hole started closing
      spontaneously. Nine months later, the hole closed and posterior hyaloid membrane
      separated from the macula. Visual acuity improved to 6/24. The purpose of this
      case report is to show that stage-II macular hole may close spontaneously with
      relief of vitreomacular traction.

PMID- 24906261
TI  - Posterior mediastinal branchial cleft cyst: an unusual site.
AB  - A two and a half year old Kenyan girl presented with recurrent chest infections
      and difficulty in swallowing. Her clinical and laboratory workup was suggestive
      of lower respiratory tract infection for which she received a course of
      antibiotics; however, she remains symptomatic after the management of her
      suspected diagnosis. Therefore, further radiological workup including a chest CT
      scan and barium study were performed. This showed a homogeneous mass surrounded
      by ascending and descending aorta in the posterior mediastinum that was
      compressing the middle esophagus. She had a posterolateral thoracotomy which
      revealed a cystic mass with smooth surfaces (5x5 cm) in the posterior
      mediastinum. Histopathology showed branchial cleft cyst predominately lined by
      stratified squamous epithelium, with lymphocytes predominance. A final diagnosis
      of posterior mediastinal branchial cleft cyst was made. She was discharged home
      and remained well at follow-up.

PMID- 24906262
TI  - Bilateral gangrene of lower limbs in a neonate.
AB  - Limb gangrene in a neonate is an extremely rare clinical problem and bilateral
      symmetrical lower limbs type is even rarer. Only few clinical cases have been
      reported thus far with idiopathic etiology or associated with rare conditions.
      Known causes in literature are sepsis, extravasation of intravenous fluid,
      following a complicated delivery and secondary to invasive monitoring. This
      report describes neonate was first developed sepsis and later was exposed to cold
      leading to bilateral gangrene of lower limbs. 

PMID- 24906263
TI  - Antenatal Bartter syndrome.
AB  - Antenatal Bartter syndrome is characterized by severe polyhydramnios in mother
      leading to premature delivery. Antenatal treatment has proven effective to
      prevent these problems. Postnatally newborns suffer from recurrent episodes of
      severe dehydration and electrolyte imbalance which can lead to fatal outcome.
      These manifestations are likely to be overlooked and missed under the umbrella of
      diagnosis of prematurity. This premature newborn with antenatal polyhydramnios
      had severe manifestations of polyuria, recurrent dehydration, electrolyte
      derangements and metabolic alkalosis. She was managed accordingly but
      unfortunately could not survive beyond 4 weeks. 

PMID- 24906264
TI  - Autoimmune lymphoproliferative syndrome with neonatal onset.
AB  - We describe 2 cases of autoimmune lymphoproliferative syndrome (ALPS), which is a
      rare disorder of auto-immunity, chronic persistent or recurrent lymphadenopathy,
      splenomegaly, hepatomegaly and hyper gamma globulinemia (1gG, 1gA). Both cases
      presented in neonatal period which is a rare age of presentation in this disease.
      A 20 days old female neonate presented with respiratory symptoms which rapidly
      progressed needing ventilatory support. There was hepatomegaly and no
      auscultatory findings in the chest. Serial CBCs (complete blood counts) showed
      persistent leucocytosis with predominant lymphocytosis. Her chest X-ray showed
      left sided consolidation which responded poorly to antibiotics. Her prompt
      clinical response to steroids raised the suspicion of autoimmunity and the
      diagnosis was established after a negative bone marrow examination for leukemia
      and a positive result for ALPS on flow cytometry. The second case presented with
      anemia, thrombocytopenia starting in neonatal period followed by persistent
      lymphadenopathy, hepatosplenomegaly and recurrent infections which responded
      poorly to antibiotics. Diagnosis was delayed due to low index of suspicion, and
      finally achieved with multiple radiological studies, histopathology and flow
      cytometry. 

PMID- 24906265
TI  - Acute cerebellitis with hydrocephalus.
AB  - We report a case of an 8 years old child who presented with sudden onset of
      headache and vomiting. He had broad-based gait and intention tremors on
      admission. MRI brain revealed isointense signals on T1-weighted imaging and
      hyperintense signals on T2-weighted imaging. Cerebellar swelling was also
      identified with significant mass effect obliterating the fourth ventricle. CT
      head showed prominent third and lateral ventricles. He was treated with high dose
      corticosteroids and required an external ventricular drain (EVD) insertion. He
      made an uneventful recovery and suffered no neurologic deficit. The clinical and
      radiologic findings in this boy were consistent with cerebellitis complicated by
      hydrocephalus. 

PMID- 24906266
TI  - Successful surgical repair of pentalogy of cantrell at 14 months of age.
AB  - Pentalogy of Cantrell with ectopia cordis is a rare congenital anomaly, first
      described in 1958 by Cantrell, has a reported incidence of around 5-10 cases per
      one million live births with wide variety of clinical presentations. We are
      reporting a child with ectopia cordis along with cleft lower sternum, upper
      abdominal wall defect, ectopic umbilicus and diaphragmatic defect.
      Echocardiography in first month of life revealed a restrictive perimembranous
      ventricular septal defect and a small patent Foramen Ovale, both closed
      spontaneously in infancy. CT angiography at 10 months of age revealed a defect in
      the thoracic and abdominal walls along with herniation of left ventricular apex
      into epigastrium. The two ventriculi formed a tail that looked like a crocodile.
      This patient underwent surgical correction at our institution at 14 months of age
      and recovered well with no residual issue.

PMID- 24906267
TI  - Prosthodontic rehabilitation of Papillon Lefevre Syndrome.
AB  - Papillon Lefevre Syndrome (PLS) is an autosomal recessive (AR) disorder affecting
      the skin and intra oral soft tissues resulting in palmo plantar hyperkeratosis
      with premature periodontal problems leading to early tooth loss and associated
      functional and psychological disturbances. This report presents management of a
      17 years old girl suffering from PLS. She was presented with the chief complaint
      of loss of many permanent teeth and mobility of the remaining teeth. Most of the
      teeth were lost very early after their eruption due to swollen infected gums.
      There were no other associated problems except for the mild burning sensation of
      the palms and soles. A decision was made and remaining teeth were extracted in
      order to prevent aggressive bone loss. She was then managed using removable
      complete dentures with bilateral balanced occlusion. The patient is comfortable
      and functioning well with her new dentition. 

PMID- 24906269
TI  - Cardiac tamponade as initial presentation in systemic lupus erythematosus.
AB  - Systemic Lupus Erythematosus (SLE) is one of the many diseases known as 'the
      great imitators' because it can have diverse presentations and so is
      misunderstood for other illnesses. This case illustrates a 19 years old girl with
      SLE who presented as cardiac tamponade which is a rare feature of lupus
      pericarditis requiring medical and surgical treatment. Even after
      pericardiocentesis and steroid therapy there was a re-accumulation of the
      pericardial fluid resulting in cardiac tamponade which led to pericardial window
      formation. This case draws attention to the need to consider the diagnosis of
      tamponade in patients with connective tissue disease and dyspnea or hemodynamic
      compromise. It also outlines the treatment options available so that surgical
      referral, if needed, can be done timely for this rare but life threatening
      manifestation of SLE. 

PMID- 24906268
TI  - Rehabilitating mandibular resection with guide flange prosthesis.
AB  - Loss of continuity of the mandible leads to deviation of the residual segment
      towards the surgical site and alteration in muscle function. This results in
      facial asymmetry and malocclusion. A corrective device known as 'guide flange
      prosthesis' is indicated to limit this clinical manifestation. Guide flange
      prosthesis serves as a training device. It can successfully guide the patient to
      close the mandible into the correct intercuspal position. This clinical report
      reveals the rehabilitation of patient who underwent hemisection of the mandible,
      subsequent to treatment for an ameloblastoma. He was successfully rehabilitated
      with mandibular guide flange prosthesis. 

PMID- 24906270
TI  - Depression and seizures as the main neuropsychiatric manifestation of mixed
      connective tissue disorder.
AB  - A 38 years female presented with arthralgia, dyspnoea, progressive proximal
      muscle weakness, seizures, weight loss, dysphagia, alopecia, and dryness of the
      eyes and mouth with tightening of the skin. Psychiatric evaluation revealed major
      depression. She had oral ulcers, tightening of the skin of the hands with
      restricted mouth opening, and proximal muscle weakness. Mixed connective tissue
      disorder (MCTD) with predominant polymyositis and neuropsychiatric manifestations
      was diagnosed as the patient had anti-RNP positive with significantly raised
      muscle enzymes. This case is unique because major depression in MCTD is rarely
      documented, severe polymyositis is a rarity and ANA was negative but
      characteristic anti-RNP antibody was positive. 

PMID- 24906271
TI  - Envenomation in pregnancy by common krait (Bungarus caeruleus).
AB  - Snakebite in pregnant women is rarely reported in medical literature. It is
      almost non-existent to the best of our knowledge involving common krait (Bungarus
      caeruleus). The case reported here involved a 30 weeks pregnant young women from
      Rawalpindi (Pakistan), with myasthenia-like syndrome. The protocol employed in
      her treatment to cure her is outlined in this report. The lady recovered,
      however, there was premature fetal birth with fatal septicaemia. 

PMID- 24906272
TI  - Fatal necrotising enterocolitis due to mydriatic eye drops.
AB  - Retinopathy of prematurity (ROP) is a serious problem of preterm infants which
      may lead to impairment of vision and even to blindness if untreated. Routine eye
      examination is necessary for early diagnosis and treatment of ROP in preterm
      infants. Mydriatic eye drops (cyclopentolate, tropicamide and phenylephrine) are
      applied before the ophthalmic examination. These agents are rarely absorbed to
      systemic circulation and in some cases result with serious side effects like skin
      rash, tachycardia, feeding intolerance, discomfort, apnea, gastric dilatation and
      ileus, despite different treatment models and dosage reducing strategies. We
      report here a preterm patient who died because of severe diffuse necrotizing
      enterocolitis (NEC) after topical application of 0.5% cyclopentolate and 1.25%
      phenylephrine during ROP screening to emphasise the serious side effects of these
      agents. 

PMID- 24906273
TI  - A rare consequence of blunt abdominal trauma: bilateral renal infarction.
AB  - A 28-year-old man was admitted to the emergency department with lumbar pain owing
      to a motorbike accident. On clinical examination, abdominal tenderness, pelvic
      and left cruris pains were present. Erythrocytes, leucocytes and protein was
      found to be positive in urine analysis. Abdominal computed tomography with
      intravenous contrast solution showed contrast enhancement in 80% of right kidney,
      and 30% of left kidney; some intra-abdominal free fluid was also seen.
      Conservative management was planned for bilateral renal infarction. Urine output
      was 1.1 L per day. He was discharged on the seventh day of the hospital stay. The
      patient had not got any problems on the sixth month follow-up. Urine output is a
      very important parameter for multiple trauma patients. Any decrease in urine
      output may not be seen inspite of the presence of bilateral renal damage as in
      the case of the patient, and this situation does not allow ruling out renal
      injury completely. Hence, emergency physician should still be careful about the
      risk of renal injury. 

PMID- 24906274
TI  - A long-forgotten indwelling single-J stent in a transplant kidney.
AB  - Ureteral stent placement is usual after renal transplantation to avoid ureteral
      obstruction and facilitate reconstruction. However, stent is prone to infection,
      encrustation, migration, fragmentation, obstruction, and even obstructive
      nephropathy with a long-indwelling time. Forgotten ureteric stent in renal
      transplant recipients is scarcely reported. Here, we present a case of long
      forgotten indwelling single-J stent for 5 years in a transplant patient. 

PMID- 24906275
TI  - Late presentation of posterior urethral valves.
AB  - Presence of posterior urethral valves (PUV) is the most common cause of urinary
      tract obstruction in the male neonate. Late presentation occurs in 10% of cases.
      We present a case of PUVs in an adult male who presented with history of
      obstructive lower urinary tract symptoms and hematuria. On evaluation, he was
      found to have raised serum creatinine level. A voiding cystourethrogram (VCUG)
      could not be completely performed because of narrowing in the posterior urethra.
      A rigid urethrocystoscopy was performed at which he was found to have type-I
      posterior urethral valve which were fulgurated. A repeat uroflowmetry revealed
      maximum flow rate of 12 ml/second. This case highlights that PUVs is not solely a
      disease of infancy but may also present late. VCUG is the radiological
      investigation of choice but the diagnosis may be missed. A urethrocystoscopy is
      advised if there is a high index of suspicion. 

PMID- 24906277
TI  - Accidental left ventricular perforation during coronary angiogram.
AB  - Myocardial perforation (MP) is an uncommon entity which occurs most commonly in
      the setting of acute myocardial infarction. We report a case of accidental left
      ventricular perforation during a routine coronary angiogram. A 55-year-old male,
      known diabetic with moderate renal impairment, non-hypertensive, suffered an
      acute inferior wall myocardial infarction for which he was thrombolyzed with
      streptokinase. Coronary angiogram was done for postmyocardial infarction angina.
      Judkin right, 6F diagnostic catheter was used for left ventriculogram. After the
      ventriculogram the patient became hemodynamically unstable. A repeat left
      ventriculogram with a 6F pigtail catheter showed a perforation of the basal
      inferoposterior wall. Two pigtail catheters were inserted into the pericardial
      cavity to relieve the pericardial tamponade. Emergency surgical repair of a 1.5
      cm rent in the inferior wall of the left ventricle was attempted. The friable and
      infarcted myocardium prevented a successful repair and the patient died after 24
      hours. 

PMID- 24906278
TI  - Adams-Oliver syndrome.
AB  - A new-born male baby with typical features of Adams-Oliver syndrome (AOS) is
      described. Adams-Oliver syndrome is the association of aplasia cutis congenita
      with terminal transverse limb reduction defects with or without cutis marmorata
      telangiectatica congenita. The patient presented with brachydactyly involving all
      the digits of his hands and shortening of both big toes along with aplasia cutis
      on the scalp. There was no systemic involvement. The patient was placed on
      regular follow-up. 

PMID- 24906279
TI  - Refeeding syndrome in a young girl with anorexia nervosa.
AB  - We report the case of a 20-year-old anorexic girl (BMI=12.9), who was
      misdiagnosed the first time and developed severe electrolyte imbalances due to
      lack of awareness about refeeding syndrome. Few cases of RS have been reported in
      literature and protocols have been suggested for prevention and management of
      this syndrome, including the awareness of circumstances in which it is most
      likely to develop, refeeding slowly and building-up micronutrient content over
      several days. Improved awareness and understanding of refeeding syndrome along
      with a well-coordinated plan are vital in delivering safe and effective
      nutritional rehabilitation. We suggest a slow and gradual increase in nutrition
      along with nutritional counselling and psychotherapy. 

PMID- 24906280
TI  - Whipple's disease.
AB  - Whipple's disease is a rare chronic multi-systemic infection, caused by Gram
      positive bacillus Tropheryma whipplei. The infection usually involves the small
      bowel, but other organs may also be involved. The diagnosis is often challenging
      and can only be made on histopathological examination. This report describes 2
      patients presenting with abdominal pain and weight loss who finally were
      diagnosed to have Whipple's disease. One of the patients was a renal transplant
      recipient. To the best of authors' knowledge, no case of Whipple's disease has
      yet been reported in Pakistan. The diagnosis were made on the basis of
      histopathological evaluation of duodenal biopsies. The cases underscore the need
      for diligent histopathological evaluation of the upper gastrointestinal biopsies
      and a high index of suspicion for an accurate diagnosis of the condition. The
      approach to the diagnosis and management of the condition is discussed. 

PMID- 24906281
TI  - Hydatid cyst of the pancreas mimicking neoplasm.
AB  - Hydatid disease is a cyclozoonotic infection caused by the cestode genus
      Echinococcus. It occurs throughout the world and is especially common in sheep-
      and cattle-raising regions of Africa, Australia, New Zealand, India, the Middle
      East, South America, and the Mediterranean. The incidence of humans infected with
      hydatid disease is approximately 1-2:1000. It is higher in rural areas. Infection
      occurs via ingestion of infected meat. Hydatidosis is caused by sheep and cattle
      ingesting tapeworm eggs in dog feces. These eggs hatch in the duodenum and invade
      the liver, lungs, or bones of sheep and cattle. Humans are infected by ingesting
      the infected meat from these animals. In the organs, the embryo transforms into a
      cyst, which develops the germinal epithelium that produces capsules, larval
      forms, and eventually the infectious scolices. Although hydatid cyst of the
      pancreas is rare, it must be considered in the differential diagnosis of
      pancreatic lesions. We present a rare case. 

PMID- 24906282
TI  - Vesicouterine fistula.
AB  - A 41 years lady presented with 13 years history of urinary incontinence alongwith
      menouria, which had developed after the first vaginal delivery. However, she had
      four normal vaginal deliveries later. Intravenous urography showed normal flow on
      both sides but there was spillage of contrast from the urinary bladder into the
      uterus, in the cystographic phase. Cystoscopy showed a fistulous opening in the
      posterior wall of bladder above the trigone. She was subjected to total abdominal
      hysterectomy with repair of the fistulous bladder opening. Postoperative recovery
      was smooth and the patient became asymptomatic. 

PMID- 24906283
TI  - Hydatidiform mole presentation as a tubal ectopic pregnancy.
AB  - Presentation of hydatidiform mole as tubal ectopic pregnancy is very rare. These
      patients usually present with ectopic pregnancy and are later diagnosed with
      hydatidiform mole on the basis of histological examination following surgery. We
      present the case of a 32-year-old female who presented with abdominal pain and
      vaginal bleed since 2 days of presentation. She was vitally stable. There was
      mild tenderness in hypogastrium and left iliac fossa. Pelvic examination showed
      mild bleeding per vaginum and fullness in both fornices. The patient was
      suspected of having an ectopic pregnancy. Ultrasonography of pelvis revealed
      fluid in cul-de-sac and a sac like mass of 1.8 cm attached to the left ovary. On
      laparotomy, there was a left sided tubal ectopic pregnancy and subsequently left
      salpingectomy was done. Histopathology of the tissue sample showed features of
      partial hydatidiform mole. Ectopic pregnancy can present as hydatidiform mole in
      rare cases for which histological examination of the tissue is required to
      establish the diagnosis. 

PMID- 24906284
TI  - Spontaneous rupture of tubal leiomyoma causing haemoperitoneum.
AB  - Leiomyomas are benign tumours that usually originate from the genital tract
      organs, particularly from the uterus. Spontaneous rupture of leiomyomas is a
      relatively rare condition. Herein, we report a 70 years old lady who was admitted
      through the emergency room with sudden abdominal pain. A ruptured mass
      originating from the fallopian tube, causing haemoperitoneum was revealed at
      laparotomy. Pathological examination revealed cellular leiomyoma. 

PMID- 24906285
TI  - Cutaneous Leishmaniasis with HIV.
AB  - Cutaneous Leishmaniasis (CL) is a vector borne disease caused by various species
      of the Leishmania parasite. CL is endemic in the province of Balochistan in
      Pakistan. In certain instances a Human Immunodeficiency Virus (HIV)-related
      immunocompromised is associated with atypical clinical presentation and
      occurrence of reactivated lesions of CL. Such presentations respond poorly to the
      standard treatment and frequent relapses are noted. We are reporting three cases
      of localized and disseminated CL due to Leishmania tropica which responded to
      meglumine antimoniate. Due to the fact that CL is endemic in Balochistan, we did
      not consider HIV infection as a causative organism. It was their presentation
      with history of weight loss and fever that prompted Enzyme-linked Immunosorbent
      Assay (ELISA) tests for HIV, which turned out to be positive. CL is becoming
      visible as an opportunistic infection associated with HIV/AIDS and may even be
      the first symptom in HIV positive patients in an endemic area. 

PMID- 24906286
TI  - Myocarditis complicating Plasmodium vivax malaria.
AB  - Myocarditis complicating Plasmodium vivax malaria is an extremely rare
      complication. We report this development in a young girl who was diagnosed to
      have P. vivax malaria on the basis of peripheral smear. While undergoing
      antimalarial treatment, she developed respiratory distress requiring invasive
      mechanical ventilation and inotropic support due to cardiogenic shock secondary
      to myocarditis. Cardiovascular complications are well recognized with Plasmodium
      falciparum malaria. Nevertheless, a high index of suspicion should be maintained
      for the same in Plasmodium vivax infection especially if symptoms of heart
      failure develop in a young patient. 

PMID- 24906287
TI  - Thyrotoxic periodic paralysis: an endocrine cause of paraparesis.
AB  - Periodic paralysis is a muscle disorder that belongs to the family of diseases
      called channelopathies, manifested by episodes of painless muscle weakness.
      Periodic paralysis is classified as hypokalemic when episodes occur in
      association with low potassium levels. Most cases are hereditary. Acquired cases
      have been described in association with hyperthyroidism. Diagnosis is made on
      clinical and biochemical grounds. Patients may be markedly hypokalemic during the
      episode and respond well to potassium supplementation. Episodes can be prevented
      by achieving a euthyroid state. This report describes a young gentleman
      presenting with thyrotoxic hypokalemic paraparesis. The condition needs to be
      considered in the differential diagnosis of neuromuscular weakness in the context
      of hypokalemia by the treating physicians. 

PMID- 24906289
TI  - Deletion of Alox5 gene decreases osteogenic differentiation but increases
      adipogenic differentiation of mouse induced pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPSCs) have great potential in bone tissue
      engineering to repair large bone defects. Before their clinical application,
      investigations are needed to discover the genes and osteoconductive scaffolds
      that influence their differentiation toward an osteogenic lineage. Alox5 plays
      controversial and complex roles in the regulation of bone and fat metabolism. To
      detect the effect of Alox5 on osteogenic and adipogenic differentiation of iPSCs,
      both Alox5 knockout mouse iPSCs (Alox5-KO-iPSCs) and wild-type mouse iPSCs (Wild
      iPSCs) were developed. The mRNA levels of many osteogenic markers in Alox5-KO
      iPSCs were significantly reduced, while many adipogenic markers were enhanced.
      Furthermore, when implanted in rat cranial critical-sized defects with
      collagen/chitosan/hydroxyapatite scaffolds (CCHS), Alox5-KO-iPSCs produced
      significantly less new bone than Wild-iPSCs and both cell-scaffold groups had no
      tumor formation. There was a significant difference in the expression of Cox2
      during the osteogenic and adipogenic differentiation between the two kinds of
      iPSCs in vitro. In conclusion, firstly, Alox5 knockout reduced the osteogenic but
      increased the adipogenic differentiation potential of mouse iPSCs. These
      disorders might be related to the change of Cox2 expression. Secondly, combined
      with iPSCs, CCHS can serve as a potential substrate to repair critical-sized bony
      defects. However, more studies are required to confirm the mechanisms through
      which Alox5 affects the osteogenic and adipogenic abilities of iPSCs in vivo and
      the effect of Cox2 inhibition in this system. 

PMID- 24906288
TI  - Multiple systemic transplantations of human amniotic mesenchymal stem cells exert
      therapeutic effects in an ALS mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive
      neurodegenerative disease involving degeneration of motor neurons in the central
      nervous system. Stem cell treatment is a potential therapy for this fatal
      disorder. The human amniotic membrane (HAM), an extremely rich and easily
      accessible tissue, has been proposed as an attractive material in cellular
      therapy and regenerative medicine because of its advantageous characteristics. In
      the present study, we evaluate the long-term effects of a cellular treatment by
      intravenous administration of human amniotic mesenchymal stem cells (hAMSCs)
      derived from HAM into a hSOD1(G93A) mouse model. The mice received systemic
      administration of hAMSCs or phosphate-buffered saline (PBS) at the onset,
      progression and symptomatic stages of the disease. hAMSCs were detected in the
      spinal cord at the final stage of the disease, in the form of isolates or
      clusters and were negative for beta-tubulin III and GFAP. Compared with the
      treatment with PBS, multiple hAMSC transplantations significantly retarded
      disease progression, extended survival, improved motor function, prevented motor
      neuron loss and decreased neuroinflammation in mice. These findings demonstrate
      that hAMSC transplantation is a promising cellular treatment for ALS. 

PMID- 24906290
TI  - Vesicular glutamate transporter 2-immunoreactive afferent nerve terminals in the
      carotid body of the rat.
AB  - The carotid body is a peripheral chemoreceptor that detects decreases in arterial
      pO2 and subsequently activates the carotid sinus nerve. The hypoxia-evoked
      activity of the carotid sinus nerve has been suggested to be modulated by
      glutamate. In the present study, we investigate the immunohistochemical
      localization of vesicular glutamate transporters in the carotid body of the rat.
      Vesicular glutamate transporter 2 (VGLUT2) labeling was closely associated with
      glomus cells immunoreactive to tyrosine hydroxylase but was not in the cytoplasm
      of these cells. The VGLUT2 immunoreactivity was observed within nerve endings
      that were immunoreactive to P2X3 and densely localized inside P2X3-immunoreactive
      axon terminals. These results suggest that VGLUT2 is localized in the afferent
      nerve terminals of the carotid body. Glutamate may be released from afferent
      nerve terminals to modulate the chemosensory activity of the carotid body. 

PMID- 24906292
TI  - The biosynthesis, composition and assembly of the outer pollen wall: A tough case
      to crack.
AB  - The formation of the durable outer pollen wall, largely composed of
      sporopollenin, is essential for the protection of the male gametophyte and plant
      reproduction. Despite its apparent strict conservation amongst land plants, the
      composition of sporopollenin and the biosynthetic pathway(s) yielding this
      recalcitrant biopolymer remain elusive. Recent molecular genetic studies in
      Arabidopsis thaliana (Arabidopsis) and rice have, however, identified key genes
      involved in sporopollenin formation, allowing a better understanding of the
      biochemistry and cell biology underlying sporopollenin biosynthesis and pollen
      wall development. Herein, current knowledge of the biochemical composition of the
      outer pollen wall is reviewed, with an emphasis on enzymes with characterized
      biochemical activities in sporopollenin and pollen coat biosynthesis. The
      tapetum, which forms the innermost sporophytic cell layer of the anther and
      envelops developing pollen, plays an essential role in sporopollenin and pollen
      coat formation. Recent studies show that several tapetum-expressed genes encode
      enzymes that metabolize fatty acid derived compounds to form putative
      sporopollenin precursors, including tetraketides derived from fatty acyl-CoA
      starter molecules, but analysis of mutants defective in pollen wall development
      indicate that other components are also incorporated into sporopollenin. Also
      highlighted are the many uncertainties remaining in the development of a
      sporopollenin-fortified pollen wall, particularly in relation to the mechanisms
      of sporopollenin precursor transport and assembly into the patterned form of the
      pollen wall. A working model for sporopollenin biosynthesis is proposed based on
      the data obtained largely from studies of Arabidopsis, and future challenges to
      complete our understanding of pollen wall biology are outlined. 

PMID- 24906291
TI  - The role of propranolol in the treatment of infantile hemangioma.
AB  - INTRODUCTION: Infantile hemangioma (IH) is one of the most common childhood
      tumors. There are various medical or surgical therapeutic options, all with
      suboptimal results. Recently, the successful use of propranolol for involution of
      IH was described. We report the results of a single-center experience with this
      therapeutic option. OBJECTIVE: To prospectively assess the efficacy and safety of
      propranolol in children with infantile hemangioma. METHODS: We performed a
      prospective analysis of clinical data of all patients with IH referred to a
      pediatric cardiology center for baseline cardiovascular assessment prior to
      propranolol therapy. Propranolol was given at a starting dose of 1 mg/kg/day and
      titrated to a target dose of 2-3 mg/kg/day according to clinical response.
      Efficacy was assessed through a photograph-based severity scoring scale. Safety
      was assessed by collecting data regarding significant side effects. RESULTS:
      Starting in 2010, 30 patients (15 female) were referred for propranolol treatment
      of IH, at a median age of six months (1-63 months). The mean target propranolol
      dose was 2.8 mg/kg/day, with a mean duration of therapy of 12 months. All
      patients experienced significant reduction of IH size and volume. There were no
      side effects. CONCLUSIONS: In our experience propranolol appears to be a useful
      and safe treatment option for severe or complicated IH, achieving a rapid and
      significant reduction in their size. No adverse effects were observed, although
      until larger clinical trials are completed, potential adverse events should be
      borne in mind and consultation with local specialists is recommended prior to
      initiating treatment.

PMID- 24906293
TI  - Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar
      structure-activity relationships.
AB  - The fungal genus Armillaria is unique in that it is the only natural source of
      melleolide antibiotics, i.e., protoilludene alcohols esterified with orsellinic
      acid or its derivatives. This class of natural products is known to exert
      antimicrobial and cytotoxic effects. Here, we present a refined relationship
      between the structure and the antimicrobial activity of the melleolides. Using
      both agar diffusion and broth dilution assays, we identified the Delta(2,4)
      double bond of the protoilludene moiety as a key structural feature for
      antifungal activity against Aspergillus nidulans, Aspergillus flavus, and
      Penicillium notatum. These findings contrast former reports on cytotoxic
      activities and may indicate a different mode of action towards susceptible fungi.
      We also report the isolation and structure elucidation of five melleolides (6'
      dechloroarnamial, 6'-chloromelleolide F, 10-hydroxy-5'-methoxy-6'
      chloroarmillane, and 13-deoxyarmellides A and B), along with the finding that
      treatment with an antifungal melleolide impacts transcription of A. nidulans
      natural product genes. 

PMID- 24906294
TI  - Magnetic resonance imaging of painful metal-on-metal total hip replacement.
AB  - Consecutive patients that had primary metal-on-metal (MoM) or metal-on
      polyethylene (MoP) hip arthroplasty were prospectively enrolled to this study.
      All operated hips were evaluated with MRI by one radiologist who was blinded to
      the radiographic findings and clinical symptoms. Three groups of patients were
      formed: (1) thirteen MoM THRs in 13 patients with groin pain (Group 1), (2) ten
      MoM THRs in 10 patients with no pain (Group 2), (3) five MoP THRs in 4 patients
      without pain (control group). Abnormal MRI findings were distributed in all
      groups in a balanced way, irrespective of the patients' symptoms, prostheses, or
      metal ion levels. Two patients from Group 1 and one patient of Group 3 (control
      group) were diagnosed with a large periprosthetic mass (pseudotumor). 

PMID- 24906295
TI  - Effects of pulsed electromagnetic field therapy on delayed-onset muscle soreness
      in biceps brachii.
AB  - OBJECTIVE: to compare the effects of pulsed electromagnetic field (PEMF) therapy
      and sham treatment on DOMS-related variables in elbow flexors at 24, 48 and 72 h
      after delayed onset muscle soreness (DOMS) induction exercise. DESIGN:
      randomized, double-blind, placebo-controlled study. SETTING: Yonsei University
      laboratory. PARTICIPANTS: In total, 30 healthy male college students. MAIN
      OUTCOME MEASURES: Muscle soreness, peak torque, median frequency (MDF) and
      electromechanical delay (EMD) during isometric contraction at 24, 48 and 72 h
      after DOMS induction exercise. RESULTS: Overall, the application of the PEMF was
      found to be effective in reducing the physiological deficits associated with
      DOMS, including improved recovery of perceived muscle soreness, MDF, and EMD
      during isometric contraction. Our results did not show that PEMF treatment was
      mechanically more effective for isometric peak torque generation compared to the
      sham group. CONCLUSION: this study indicates that PEMF may be useful as a
      modality to reduce DOMS symptoms. However, further well-designed experiments are
      required to determine optimal treatment dosage and duration, and to investigate
      the physiological and clinical mechanisms of PEMF on DOMS.

PMID- 24906296
TI  - A touch panel surgical navigation system with automatic depth perception.
AB  - PURPOSE: A touch panel navigation system may be used to enhance endoscopic
      surgery, especially for cauterization. We developed and tested the in vitro
      performance of a new touch panel navigation (TPN) system. METHODS: This TPN
      system uses finger motion trajectories on a touch panel to control an argon
      plasma coagulation (APC) attached to a robot arm. Thermal papers with printed
      figures were soaked in saline for repeated recording and analysis of cauterized
      trajectory. A novice and an expert surgeon traced squares and circles displayed
      on the touch panel and cauterized them using the APC. Sixteen novices and eight
      experts cauterized squares and circles using both conventional endoscopic and TPN
      procedures. Six novices cauterized arcs using the endoscopic and TPN procedures
      20 times a day for 5 consecutive days. RESULTS: For square shapes, the offset was
      5.5 mm with differences between the novice and the expert at 2 of 16 points. For
      circles, the offset was 5.0 mm and did not differ at any point. Task completion
      time for the TPN procedure was significantly longer than that for the endoscopic
      procedure for both squares and circles. For squares, the distance from the target
      for the TPN procedure was significantly smaller than that for the endoscopic
      procedure. For circles, the distance did not differ. There was no difference in
      task completion time and distance between the novices and the experts. Task
      completion time and distance improved significantly for the endoscopic procedure
      but not for the TPN procedure. CONCLUSIONS: A new TPN system enabled the surgeons
      to accomplish continuous 3D positioning of the surgical device with automatic
      depth perception using finger tracing on a 2D monitor. This technology is
      promising for application in surgical procedures that require precise control of
      cauterization.

PMID- 24906297
TI  - Single dose varenicline may trigger epileptic activity.
AB  - Varenicline is a new drug for smoking cessation, and its effect on epilepsy is
      not clear. The aim of this study was to investigate whether different doses of
      varenicline cause epileptic activity. Forty rats were randomly assigned to the
      following eight groups: control, saline, and 0.025, 0.04, 0.1, 0.5, 1, and 2 mg
      kg(-1) varenicline (single dose, i.p.). EEGs were recorded before the varenicline
      injection and during the following 240 min. While epileptic discharges were
      observed on the EEGs of the rats in all of the varenicline-treated groups, motor
      findings of epileptic seizure were not observed in some rats in these groups
      except the 1 and 2 mg kg(-1) groups. These findings indicate that different
      single doses of varenicline cause epileptic activity in rats.

PMID- 24906298
TI  - Efficient de novo assembly of large and complex genomes by massively parallel
      sequencing of Fosmid pools.
AB  - BACKGROUND: Sampling genomes with Fosmid vectors and sequencing of pooled Fosmid
      libraries on the Illumina platform for massive parallel sequencing is a novel and
      promising approach to optimizing the trade-off between sequencing costs and
      assembly quality. RESULTS: In order to sequence the genome of Norway spruce,
      which is of great size and complexity, we developed and applied a new technology
      based on the massive production, sequencing, and assembly of Fosmid pools (FP).
      The spruce chromosomes were sampled with ~40,000 bp Fosmid inserts to obtain
      around two-fold genome coverage, in parallel with traditional whole genome
      shotgun sequencing (WGS) of haploid and diploid genomes. Compared to the WGS
      results, the contiguity and quality of the FP assemblies were high, and they
      allowed us to fill WGS gaps resulting from repeats, low coverage, and allelic
      differences. The FP contig sets were further merged with WGS data using a novel
      software package GAM-NGS. CONCLUSIONS: By exploiting FP technology, the first
      published assembly of a conifer genome was sequenced entirely with massively
      parallel sequencing. Here we provide a comprehensive report on the different
      features of the approach and the optimization of the process.We have made public
      the input data (FASTQ format) for the set of pools used in this
      study:ftp://congenie.org/congenie/Nystedt_2013/Assembly/ProcessedData/FosmidPools
      .(alternatively accessible via http://congenie.org/downloads).The software used
      for running the assembly process is available at
      http://research.scilifelab.se/andrej_alexeyenko/downloads/fpools/.

PMID- 24906299
TI  - Assessing the performance of curtain flow first generation silica monoliths.
AB  - Analytical scale active flow technology first generation silica monolithic
      columns kitted out in curtain flow mode of operation were studied for the first
      time. A series of tests were undertaken assessing the column efficiency, peak
      asymmetry and detection sensitivity. Two curtain flow columns were tested, one
      with a fixed outlet ratio of 10% through the central exit port, the other with
      30%. Tests were carried out using a wide range in inlet flow segmentation ratios.
      The performance of the curtain flow columns were compared to a conventional
      monolithic column. The gain in theoretical plates achieved in the curtain flow
      mode of operation was as much as 130%, with almost Gaussian bands being obtained.
      Detection sensitivity increased by as much as 250% under optimal detection
      conditions. The permeability advantage of the monolithic structure together with
      the active flow technology makes it a priceless tool for high throughput,
      sensitive, low detection volume analyses. 

PMID- 24906302
TI  - Annexin V magnetic-activated cell sorting versus swim-up for the selection of
      human sperm in ART: is the new approach better then the traditional one?
AB  - PURPOSE: To investigate whether the sperm fertilizing potential can be improved
      by selecting a non-apoptotic fraction using magnetic activated cell sorting
      (MACS), and to compare the results with the conventional swim-up method. METHODS:
      Twenty five male patients attending the andrology laboratory for sperm DNA
      fragmentation analysis. The sperm were prepared by density gradient
      centrifugation (DGC) and subsequently divided into three aliquots. The first was
      further separated into Annexin V-negative (non-apoptotic) fraction using MACS,
      the second was further processed by swim-up, while the third was left unseparated
      as a control. The impact of the combination of DGC with the two sperm preparation
      techniques on sperm quality was evaluated by comparing 'rapid progressive'
      motility, normal morphology according to Tygerberg's strict criteria and DNA
      integrity (by terminal deoxynucleotide transferase-mediated dUTP nick-end
      labeling [TUNEL]) for each aliquot. RESULTS: Sperm preparation that combines DGC
      with conventional swim-up method can provide sperm of higher quality in terms of
      motility, morphology and extent of DNA fragmentation compared to the Annexin V
      negative (non-apoptotic) fraction derived from the combination of DGC with MACS.
      CONCLUSIONS: Integrating MACS as a part of sperm preparation technique will not
      improve sperm fertilizing potential to the same extent as the traditional swim-up
      separation procedure.

PMID- 24906303
TI  - ED50 and ED90 of intrathecal hyperbaric 2% prilocaine in ambulatory knee
      arthroscopy.
AB  - PURPOSE: Hyperbaric 2% prilocaine (HP) is increasingly used for spinal anesthesia
      in day-case surgery. The aim of this prospective double-blind study was to
      determine the effective dose (ED)50 and the ED90 of HP for patients undergoing
      knee arthroscopy. METHODS: Doses of HP were determined using an up-and-down
      sequential allocation technique. Sequences were analyzed by isotonic regression
      analysis. A subsequent observational study was performed with the calculated ED90
      in 50 patients to confirm the initial result and to describe the induced blockade
      effects and side effects. Times corresponding to onset and duration of sensory
      and motor block, surgical data, and side effects were recorded. RESULTS: The ED50
      was estimated at 28.9 mg (95% confidence interval [CI]: 26.5 to 35.3) and the
      ED90 was estimated to be 38.5 mg (95% CI: 35.7 to 39.5). A 40 mg dose of HP
      provided efficient anesthesia in 46 patients (92%, 95% CI: 82 to 98). The average
      (SD) time to effective anesthesia was 14.5 (3.9) min. Complete sensory block at
      level T12 was obtained after ten minutes in 44 of 50 patients. The average (SD)
      duration of the sensory block was 205 (36.1) min. Maximal level of sensory block
      was obtained at the T8-T11 levels in 41 of 50 patients without hemodynamic
      instability. A Bromage 3 score was obtained in 40 of the 46 patients who achieved
      successful anesthesia after 30 min. Patients did not experience urinary
      retention, nor were any signs of transient neurologic symptoms observed.
      CONCLUSION: This study determined the ED50 of HP is 28.9 mg and suggests that a
      40-mg dose of HP is adequate to provide successful spinal anesthesia for
      outpatient knee arthroscopy.

PMID- 24906304
TI  - Comparative efficacy of uterotonic agents: in vitro contractions in isolated
      myometrial strips of labouring and non-labouring women.
AB  - PURPOSE: To compare the in vitro contractile responses to oxytocin, ergonovine,
      prostaglandin F2 alpha (PGF2alpha), and misoprostol in isolated myometrium from
      non-labouring and labouring pregnant women. METHODS: Myometrial strips obtained
      from labouring (with or without oxytocin augmentation) and non-labouring women
      undergoing Cesarean deliveries were subjected to a dose-response testing with
      oxytocin, ergonovine, PGF2alpha, or misoprostol (10(-10) M to 10(-5) M). The
      amplitude and frequency of contractions, motility index (MI) (amplitude *
      frequency), and area under the curve during the dose-response period were
      recorded. The primary outcome was the motility index. Data were analyzed using
      linear regression models. RESULTS: We performed 130 experiments in myometrial
      strips obtained from 46 women. The overall MI (?gram.contractions.10 min(-1)
      [?g.c.10 min(-1)]) was greatest for oxytocin (mean 5.10 ?g.c.10 min(-1); 95%
      confidence interval [CI] 4.70 to 5.50) than for ergonovine (mean 3.46 ?g.c.10
      min(-1); 95% CI 3.13 to 3.80; P < 0.001), PGF2alpha (mean 2.64 ?g.c.10 min(-1);
      95% CI 2.40 to 2.87; P < 0.001), and misoprostol (2.52 ?g.c.10 min(-1); 95% CI
      2.22 to 2.82; P < 0.001). The MI for oxytocin was significantly lower in
      augmented labour (mean 4.11 ?g.c.10 min(-1); 95% CI 3.48 to 4.73) than in non
      augmented labour (mean 5.19 ?g.c.10 min(-1); 95% CI 4.39 to 6.00; P = 0.04) or in
      absence of labour (mean 5.80 ?g.c.10 min(-1); 95% CI 5.36 to 6.24; P < 0.001).
      Nevertheless, in augmented labour, oxytocin still produced superior contractions
      compared with other uterotonic drugs. Responses to ergonovine, PGF2alpha, and
      misoprostol were unaffected by labour or prior exposure to oxytocin. CONCLUSION:
      Oxytocin induces superior myometrial contractions compared with ergonovine,
      PGF2alpha, and misoprostol. The effect of oxytocin is reduced in myometrium of
      women with oxytocin-augmented labour; however, it is still superior to the other
      uterotonics. This trial was registered at ClinicalTrials.gov: NCT01689311.

PMID- 24906305
TI  - A systematic review of types of healthy eating interventions in preschools.
AB  - BACKGROUND: With the worldwide levels of obesity new venues for promotion of
      healthy eating habits are necessary. Considering children's eating habits are
      founded during their preschool years early educational establishments are a
      promising place for making health promoting interventions. METHODS: This
      systematic review evaluates different types of healthy eating interventions
      attempting to prevent obesity among 3 to 6 year-olds in preschools, kindergartens
      and day care facilities. Studies that included single interventions, educational
      interventions and/or multicomponent interventions were eligible for review.
      Included studies also had to have conducted both baseline and follow-up
      measurements.A systematic search of the databases Scopus, Web of Science, CINAHL
      and PubMed was conducted to identify articles that met the inclusion criteria.
      The bibliographies of identified articles were also searched for relevant
      articles. RESULTS: The review identified 4186 articles, of which 26 studies met
      the inclusion criteria. Fifteen of the interventions took place in preschools, 10
      in kindergartens and 1 in another facility where children were cared for by
      individuals other than their parents. Seventeen of the 26 included studies were
      located in North America, 1 in South America, 5 in Asia, and 3 in a European
      context.Healthy eating interventions in day care facilities increased fruit and
      vegetable consumption and nutrition related knowledge among the target groups.
      Only 2 studies reported a significant decrease in body mass index. CONCLUSIONS:
      This review highlights the scarcity of properly designed healthy eating
      interventions using clear indicators and verifiable outcomes. The potential of
      preschools as a potential setting for influencing children's food choice at an
      early age should be more widely recognised and utilised.

PMID- 24906306
TI  - Cell cycle-regulated transcription: effectively using a genomics toolbox.
AB  - The cell cycle comprises a series of temporally ordered events that occur
      sequentially, including DNA replication, centrosome duplication, mitosis, and
      cytokinesis. What are the regulatory mechanisms that ensure proper timing and
      coordination of events during the cell cycle? Biochemical and genetic screens
      have identified a number of cell-cycle regulators, and it was recognized early on
      that many of the genes encoding cell-cycle regulators, including cyclins, were
      transcribed only in distinct phases of the cell cycle. Thus, "just in time"
      expression is likely an important part of the mechanism that maintains the proper
      temporal order of cell cycle events. New high-throughput technologies for
      measuring transcript levels have revealed that a large percentage of the
      Saccharomyces cerevisiae transcriptome (~20 %) is cell cycle regulated.
      Similarly, a substantial fraction of the mammalian transcriptome is cell cycle
      regulated. Over the past 25 years, many studies have been undertaken to determine
      how gene expression is regulated during the cell cycle. In this review, we
      discuss contemporary models for the control of cell cycle-regulated
      transcription, and how this transcription program is coordinated with other cell
      cycle events in S. cerevisiae. In addition, we address the genomic approaches and
      analytical methods that enabled contemporary models of cell cycle transcription.
      Finally, we address current and future technologies that will aid in further
      understanding the role of periodic transcription during cell cycle progression. 

PMID- 24906308
TI  - Interplay between the cell cycle and double-strand break response in mammalian
      cells.
AB  - The cell cycle is intimately associated with the ability of cells to sense and
      respond to and repair DNA damage. Understanding how cell cycle progression,
      particularly DNA replication and cell division, are regulated and how DNA damage
      can affect these processes has been the subject of intense research. Recent
      evidence suggests that the repair of DNA damage is regulated by the cell cycle,
      and that cell cycle factors are closely associated with repair factors and
      participate in cellular decisions regarding how to respond to and repair damage.
      Precise regulation of cell cycle progression in the presence of DNA damage is
      essential to maintain genomic stability and avoid the accumulation of chromosomal
      aberrations that can promote tumor formation. In this review, we discuss the
      current understanding of how mammalian cells induce cell cycle checkpoints in
      response to DNA double-strand breaks. In addition, we discuss how cell cycle
      factors modulate DNA repair pathways to facilitate proper repair of DNA lesions. 

PMID- 24906307
TI  - Cell cycle regulation by checkpoints.
AB  - Cell cycle checkpoints are surveillance mechanisms that monitor the order,
      integrity, and fidelity of the major events of the cell cycle. These include
      growth to the appropriate cell size, the replication and integrity of the
      chromosomes, and their accurate segregation at mitosis. Many of these mechanisms
      are ancient in origin and highly conserved, and hence have been heavily informed
      by studies in simple organisms such as the yeasts. Others have evolved in higher
      organisms, and control alternative cell fates with significant impact on tumor
      suppression. Here, we consider these different checkpoint pathways and the
      consequences of their dysfunction on cell fate. 

PMID- 24906309
TI  - Cell cycle regulation by protein degradation.
AB  - Cell division is controlled by a highly regulated program to accurately duplicate
      and segregate chromosomes. An important feature of the cell cycle regulatory
      program is that key cell cycle proteins are present and active during specific
      cell cycle stages but are later removed or inhibited to maintain appropriate
      timing. The ubiquitin-proteasome system has emerged as an important mechanism to
      target cell cycle proteins for degradation at critical junctures during cell
      division. Two key E3 ubiquitin ligase complexes that target key cell cycle
      proteins are the Skp1-Cul1-F-box protein complex and the anaphase-promoting
      complex/cyclosome. This chapter focuses on the role of these E3 ubiquitin ligases
      and how ubiquitin-dependent degradation of central cell cycle regulatory proteins
      advances the cell cycle.

PMID- 24906311
TI  - The Greatwall-PP2A axis in cell cycle control.
AB  - Cell cycle progression is largely controlled by reversible protein
      phosphorylation mediated by cyclically activated kinases and phosphatases. It has
      long been known that cyclin B-Cdk1 activation triggers mitotic entry, and the
      enzymatic network controlling its activation and inactivation has been well
      characterized. Much more recently protein phosphatase 2A (PP2A) together with its
      B55 regulatory subunit has been recognized as the major activity
      dephosphorylating Cdk1 targets. Moreover, PP2A-B55 activity is high in late M
      phase and interphase, but low at mitotic entry. A series of discoveries in the
      fly and frog model systems have uncovered the molecular mechanism mediating this
      regulation. The Greatwall (Gwl) kinase activates endosulfines, which become
      specific inhibitors of PP2A-B55. Cdk1-dependent activation of Gwl at mitotic
      entry leads to PP2A-B55 downregulation, which synergizes with Cdk1 activation to
      promote the phosphorylated states of several mitotic substrates. Much less is
      known on the mechanisms inactivating Gwl and endosulfines at mitotic exit. Recent
      reports show the importance of spatiotemporal regulation of Gwl, endosulfines,
      and PP2A-B55 for cell cycle progression. The various systems and cell types
      differ in their dependence on the Gwl-PP2A axis for cell cycle progression.
      Moreover, this pathway also regulates gene expression in yeast, and this function
      could be conserved in metazoans.

PMID- 24906313
TI  - The senescence arrest program and the cell cycle.
AB  - All living organisms are subject to progressive loss of function and damage to
      their tissues, a process known as aging. At the cellular level, the accumulation
      of damage to DNA, proteins, and organelles induces cellular senescence, a stress
      response pathway that likely influences the aging process. Although the
      senescence arrest program was initially described in vitro, accumulating evidence
      suggests that this damage response program occurs in a variety of pathologic
      settings. This review discusses aspects of the senescence program, their
      interrelationships with damage arrest pathways, the cell cycle, and the impact of
      senescence in vivo. 

PMID- 24906312
TI  - Cell cycle regulation by the nutrient-sensing mammalian target of rapamycin
      (mTOR) pathway.
AB  - Cell division involves a series of ordered and controlled events that lead to
      cell proliferation. Cell cycle progression implies not only demanding amounts of
      cell mass, protein, lipid, and nucleic acid content but also a favorable energy
      state. The mammalian target of rapamycin (mTOR), in response to the energy state,
      nutrient status, and growth factor stimulation of cells, plays a pivotal role in
      the coordination of cell growth and the cell cycle. Here, we review how the
      nutrient-sensing mTOR-signaling cascade molecularly integrates nutritional and
      mitogenic/anti-apoptotic cues to accurately coordinate cell growth and cell
      cycle. First, we briefly outline the structure, functions, and regulation of the
      mTOR complexes (mTORC1 and mTORC2). Second, we concisely evaluate the best known
      ability of mTOR to control G1-phase progression. Third, we discuss in detail the
      recent evidence that indicates a new genome stability caretaker function of mTOR
      based on the specific ability of phosphorylated forms of several mTOR-signaling
      components (AMPK, raptor, TSC, mTOR, and S6K1), which spatially and temporally
      associate with essential mitotic regulators at the mitotic spindle and at the
      cytokinetic cleavage furrow.

PMID- 24906314
TI  - Oncogenic Ras pushes (and pulls) cell cycle progression through ERK activation.
AB  - The Ras-Raf-MEK-ERK signaling cascade is capable of channeling a wide variety of
      extracellular signals into control of cell proliferation, differentiation,
      senescence, and death. Because aberrant regulation at all steps of this signaling
      axis is observed in cancer, it remains an area of great interest in the field of
      tumor biology. Here we present evidence of the intricate and delicate levels of
      control of this pathway as it pertains to cell cycle regulation and illustrate
      how this control is not simply a rheostat. 

PMID- 24906310
TI  - Linking chromosome duplication and segregation via sister chromatid cohesion.
AB  - DNA replication during S phase generates two identical copies of each chromosome.
      Each chromosome is destined for a daughter cell, but each daughter must receive
      one and only one copy of each chromosome. To ensure accurate chromosome
      segregation, eukaryotic cells are equipped with a mechanism to pair the
      chromosomes during chromosome duplication and hold the pairs until a bi-oriented
      mitotic spindle is formed and the pairs are pulled apart. This mechanism is known
      as sister chromatid cohesion, and its actions span the entire cell cycle. During
      G1, before DNA is copied during S phase, proteins termed cohesins are loaded onto
      DNA. Paired chromosomes are held together through G2 phase, and finally the
      cohesins are dismantled during mitosis. The processes governing sister chromatid
      cohesion ensure that newly replicated sisters are held together from the moment
      they are generated to the metaphase-anaphase transition, when sisters separate. 

PMID- 24906315
TI  - Cell cycle regulation during viral infection.
AB  - To replicate their genomes in cells and generate new progeny, viruses typically
      require factors provided by the cells that they have infected. Subversion of the
      cellular machinery that controls replication of the infected host cell is a
      common activity of many viruses. Viruses employ different strategies to
      deregulate cell cycle checkpoint controls and modulate cell proliferation
      pathways. A number of DNA and RNA viruses encode proteins that target critical
      cell cycle regulators to achieve cellular conditions that are beneficial for
      viral replication. Many DNA viruses induce quiescent cells to enter the cell
      cycle; this is thought to increase pools of deoxynucleotides and thus, facilitate
      viral replication. In contrast, some viruses can arrest cells in a particular
      phase of the cell cycle that is favorable for replication of the specific virus.
      Cell cycle arrest may inhibit early cell death of infected cells, allow the cells
      to evade immune defenses, or help promote virus assembly. Although beneficial for
      the viral life cycle, virus-mediated alterations in normal cell cycle control
      mechanisms could have detrimental effects on cellular physiology and may
      ultimately contribute to pathologies associated with the viral infection,
      including cell transformation and cancer progression and maintenance. In this
      chapter, we summarize various strategies employed by DNA and RNA viruses to
      modulate the replication cycle of the virus-infected cell. When known, we
      describe how these virus-associated effects influence replication of the virus
      and contribute to diseases associated with infection by that specific virus.

PMID- 24906317
TI  - Introductory review of computational cell cycle modeling.
AB  - Recent advances in the modeling of the cell cycle through computer simulation
      demonstrate the power of systems biology. By definition, systems biology has the
      goal to connect a parts list, prioritized through experimental observation or
      high-throughput screens, by the topology of interactions defining intracellular
      networks to predict system function. Computer modeling of biological systems is
      often compared to a process of reverse engineering. Indeed, designed or
      engineered technical systems share many systems-level properties with biological
      systems; thus studying biological systems within an engineering framework has
      proven successful. Here we review some aspects of this process as it pertains to
      cell cycle modeling. 

PMID- 24906318
TI  - Cell cycle synchronization and flow cytometry analysis of mammalian cells.
AB  - Analysis of cellular DNA content and measurement of pulse-labeled newly
      replicated DNA by flow cytometry are useful techniques for cell cycle studies. In
      this chapter, we describe the protocols for cell cycle synchronization of
      mammalian cells, including time course designs and consideration of cell types to
      achieve successful experiments, along with the methods for detection of DNA. Some
      selected applications dealing with siRNA-mediated knockdown are also presented. 

PMID- 24906319
TI  - Analyzing transcription dynamics during the budding yeast cell cycle.
AB  - Assaying global cell cycle-regulated transcription in budding yeast involves
      extracting RNA from a synchronous population and proper normalization of detected
      transcript levels. Here, we describe synchronization of Saccharomyces cerevisiae
      cell populations by centrifugal elutriation, followed by the isolation of RNA for
      microarray analysis. Further, we outline the computational methods required to
      directly compare RNA abundance from individual time points within an experiment
      and to compare independent experiments. Together, these methods describe the
      complete workflow necessary to observe RNA abundance during the cell cycle. 

PMID- 24906320
TI  - Analyzing cell cycle checkpoints in response to ionizing radiation in mammalian
      cells.
AB  - Exposure of cells to DNA-damaging agents, such as ionizing radiation (IR),
      results in perturbation of cell cycle progression. IR activates cell cycle
      checkpoints that arrest the cell cycle at the G1/S, S, and G2/M phases. The DNA
      damage-signaling network involves a number of important DNA damage response
      factors that are required for maintaining genome stability and prevention of
      cancer. These factors are involved in the regulation of cell cycle checkpoints
      and include ATM, NBS1, BRCA1, Chk2, and p53. Here we describe a series of assays
      that are often used to analyze cell cycle checkpoints after IR. These assays
      include a G1/S checkpoint assay that measures 5-bromodeoxyuridine incorporation
      into DNA, an S-phase checkpoint assay that measures DNA synthesis at a very early
      time point after IR, and a G2/M checkpoint assay that quantitates histone H3
      phosphorylation. This collection of assays allows us to investigate the specific
      functions of proteins involved in regulating different cell cycle checkpoints in
      mammalian cells as a response to IR. 

PMID- 24906316
TI  - The roles of cohesins in mitosis, meiosis, and human health and disease.
AB  - Mitosis and meiosis are essential processes that occur during development.
      Throughout these processes, cohesion is required to keep the sister chromatids
      together until their separation at anaphase. Cohesion is created by multiprotein
      subunit complexes called cohesins. Although the subunits differ slightly in
      mitosis and meiosis, the canonical cohesin complex is composed of four subunits
      that are quite diverse. The cohesin complexes are also important for DNA repair,
      gene expression, development, and genome integrity. Here we provide an overview
      of the roles of cohesins during these different events as well as their roles in
      human health and disease, including the cohesinopathies. Although the exact roles
      and mechanisms of these proteins are still being elucidated, this review serves
      as a guide for the current knowledge of cohesins.

PMID- 24906321
TI  - Analyzing DNA replication checkpoint in budding yeast.
AB  - Checkpoints are conserved mechanisms that prevent progression into the next phase
      of the cell cycle when cells are unable to accomplish the previous event
      properly. Cells also possess a surveillance mechanism called the DNA replication
      checkpoint, which consists of a conserved kinase cascade that is provoked by
      insults that block or slow down replication fork progression. In the budding
      yeast Saccharomyces cerevisiae, the DNA replication checkpoint controls the
      timing of S-phase events such as origin firing and spindle elongation. This
      checkpoint also upregulates dNTP pools and maintains the replication fork
      structure in order to resume DNA replication after replication block. Many
      replication checkpoint factors have been found to be tumor suppressors,
      highlighting the importance of this checkpoint pathway in human health. Here we
      describe a series of protocols to analyze the DNA replication checkpoint in S.
      cerevisiae. 

PMID- 24906322
TI  - Analyzing cell cycle-dependent degradation and ubiquitination in budding yeast.
AB  - Cell cycle progression is tightly regulated to prevent uncontrolled growth and
      division. Specific cell cycle factors are responsible for driving the cell from
      one cell cycle stage to the next. Many of these proteins are targeted for
      degradation by the ubiquitin proteasome system when their function is no longer
      required or may disrupt cell cycle progression. Here we describe a series of
      experiments used to study the ubiquitin-mediated degradation of cell cycle
      proteins. This collection of assays may be used to determine the requirement for
      individual proteins in the degradation and ubiquitination of cell cycle proteins
      in Saccharomyces cerevisiae. 

PMID- 24906323
TI  - Imaging analysis of cell cycle-dependent degradation of Cdt1 in mammalian cells.
AB  - Numerous cell cycle-regulating proteins are controlled by protein degradation.
      Recent work shows that ubiquitination-dependent proteolysis plays an important
      role in once-per-cell cycle control of DNA replication. Cdt1 is a licensing
      factor essential for assembling the pre-replicative complex on replication
      origins. Cdt1 is present in G1 phase, but after S phase ubiquitin-mediated
      proteolysis maintains Cdt1 at low levels. This is important to prevent the re
      replication of chromosomal DNA. The cell cycle-dependent degradation of Cdt1 can
      be monitored by dual staining of the cell nuclei with antibodies against Cdt1-
      and S/G2-phase marker proteins, such as cyclin A or geminin.

PMID- 24906324
TI  - PCNA-dependent ubiquitination of Cdt1 and p21 in mammalian cells.
AB  - PCNA is a DNA clamp, acting on chromatin as a platform for various proteins
      involved in many aspects of DNA replication-linked processes. Most of these
      proteins have the PCNA-interaction protein motif (PIP box) that associates with
      PCNA. Recent works show that PCNA plays an important role as a matchmaker,
      connecting PCNA-interacting proteins to the ubiquitin ligase CRL4(Cdt2) for their
      degradation. Proteins degraded by CRL4(Cdt2) include Cdt1, p21, and Set8 in
      mammalian cells. These CRL4(Cdt2) substrates have a PIP degron that consists of
      the canonical PIP-box sequence and additional conserved amino acids required for
      ubiquitination. The degradation of these proteins is triggered when PCNA is
      loaded onto chromatin at the onset of S phase, and this process is important to
      prevent re-replication of DNA. These CRL4(Cdt2) substrates are also degraded
      through the same mechanism in response to DNA damage. In this chapter, we
      describe several approaches to investigate how PIP degron-containing proteins are
      degraded in a PCNA-dependent manner.

PMID- 24906325
TI  - Analyzing Cdc2/Cdk1 activation during stress response in Schizosaccharomyces
      pombe.
AB  - Stress leads to multiple changes in the physiology of the cell. One of the most
      important is the adaptation of the cell cycle to the changing conditions of the
      environment. Cellular responses after stress can be followed by cellular
      synchronization previous to the insult. In this chapter, we use centrifugal
      elutriation to synchronize Schizosaccharomyces pombe cells and outline methods to
      investigate the hallmarks of cell cycle progression upon stress. These include
      analyses of cyclin-dependent kinase phosphorylation and cell size change. 

PMID- 24906326
TI  - Analyzing Ras-associated cell proliferation signaling.
AB  - Ras-dependent signaling is an important regulator of cell cycle progression,
      proliferation, senescence, and apoptosis. Several of the downstream effectors of
      Ras play dual roles in each of these processes. Under one set of conditions, they
      promote cell cycle progression and proliferation; yet, in a different paradigm,
      they drive cell cycle arrest and apoptosis. Furthermore, there is cross talk
      between certain downstream effectors of Ras including the PI3K-AKT and Raf-MEK
      ERK pathways. Here we describe a series of experiments used to dissect the effect
      of different Ras-dependent signaling pathways on cell cycle progression,
      proliferation, senescence, and apoptosis. Furthermore, we highlight the
      importance of consistent growth conditions of cells in culture when studying Ras
      dependent signaling as we show that the activation of downstream effectors of Ras
      changes with the confluency at which the cells are grown.

PMID- 24906327
TI  - Telomere regulation during the cell cycle in fission yeast.
AB  - The fission yeast Schizosaccharomyces pombe has emerged as a useful model
      organism to study telomere maintenance mechanisms. In this chapter, we provide
      detailed protocols for quantitative ChIP and BrdU incorporation analyses to
      investigate how fission yeast telomeres are regulated during the cell cycle by
      utilizing cdc25-22 synchronized cell cultures. 

PMID- 24906328
TI  - Detecting senescence: methods and approaches.
AB  - The detection of senescent cells has become an important area of research in the
      aging field. Due to the complexity of the senescence program and the lack of a
      unique signature for senescence, the detection of these cells remains
      problematic. This is especially true for in vivo detection in aged or diseased
      tissue samples. This chapter outlines approaches for the detection of senescent
      cells based upon methods established for mesenchymal cells in culture. A stepwise
      approach to the detection of senescent cells using multiple techniques is
      provided. 

PMID- 24906329
TI  - Analyzing RB and E2F during the G1-S transition.
AB  - The G1/S-phase restriction point is an important landmark in the mammalian cell
      division cycle. The key regulator of the G1/S transition is the retinoblastoma
      gene product (pRB). It prevents the transcription of genes required for S-phase
      progression by repressing E2F transcription factors. An increase in Cdk
      phosphorylation of pRB causes the release of E2F transcription factors and
      advancement into S phase. Here we describe two simple techniques used to assess
      pRB phosphorylation and E2F transcription during G1/S progression.

PMID- 24906330
TI  - Analyzing G1-S transcriptional control.
AB  - G1-S transcriptional control involves the coordination of the expression of a
      large set of co-regulated genes as a function of cell cycle progression (Bertoli
      et al., Nat Rev Mol Cell Biol 14:518-528, 2013). Confining transcription to the
      G1 phase of the cell cycle requires the regulation of specific transcription
      factor activity through either co-factors or regulation of promoter DNA binding.
      Therefore, the analysis of G1-S transcriptional control involves cell cycle
      synchronization and monitoring cell cycle synchrony, in order to establish DNA
      binding of G1-S transcription factors to G1-S promoters and to investigate
      changes in gene expression during the different phases of the cell cycle. Here,
      we describe a cell cycle synchrony method and ways to monitor synchrony. We also
      describe a chromatin immunoprecipitation (ChIP) method to locate G1-S
      transcription factor components to promoters and a quantitative PCR (qPCR)
      protocol to determine gene expression. Defining the binding dynamics of G1-S
      transcription factors and changes in gene expression during the cell cycle should
      provide new insights into the mechanism that control G1-S transcription and will
      allow for investigation of the biological relevance of confining gene expression
      to G1. 

PMID- 24906331
TI  - Analysis of replication timing using synchronized budding yeast cultures.
AB  - Eukaryotic DNA replication exhibits at once extraordinary fidelity and
      substantial plasticity. The importance of the apparent presence of a replication
      temporal program on a population level has been the subject of intense debate of
      late. Such debate has been, to a great extent, facilitated by methods that permit
      the description and analysis of replication dynamics in various model organisms,
      both globally and at a single-molecule level. Each of these methods provides a
      unique view of the replication process, and also presents challenges and
      questions in the interpretation of experimental observations. Thus, wider
      applications of these methods in different genetic backgrounds and in different
      organisms would doubtless enable us to better understand the execution and
      regulation of chromosomal DNA synthesis as well as its impact on genome
      maintenance. 

PMID- 24906333
TI  - Chromatin fractionation analysis of licensing factors in mammalian cells.
AB  - ORC, Cdc6, Cdt1, and MCM2-7 are replication-licensing factors, which play a
      central role in the once-per-cell cycle control of DNA replication. ORC, Cdc6,
      and Cdt1 collaborate to load MCM2-7 onto replication origins in order to license
      them for replication. MCM2-7 is a DNA helicase directly involved in DNA
      replication and dissociates from DNA as S phase progresses and each replicon is
      replicated. In the cell cycle, the loading of MCM2-7 is restricted during the end
      of mitosis and the G1 phase. Thus, the levels of chromatin-bound MCM2-7 and its
      loaders oscillate during the cell cycle. Chromatin association of these factors
      can be analyzed by separating a cell lysate into soluble and chromatin-enriched
      insoluble fractions in mammalian cells. 

PMID- 24906332
TI  - Analysis of ssDNA gaps and DSBs in genetically unstable yeast cultures.
AB  - DNA replication defects are an underlying cause of genome instability, which
      could stem from alterations in replication intermediates such as extensive single
      stranded DNA (ssDNA). Under replication stress, ssDNA is a precursor of the
      ultimate double-strand breaks (DSBs). Indeed, mutations that render the cell
      incapable of mediating and protecting the replication forks produce ssDNA genome
      wide at high frequency and cause lethality when encountering DNA damage or
      replication perturbation. Here we describe two related microarray-based methods
      to query genetically unstable yeast cultures, such as the mec1 and rad53 mutants.
      These mutants are defective in central protein kinases in the checkpoint pathway.
      To induce ssDNA and DSB formation in these mutants, we utilize hydroxyurea, a
      drug that causes nucleotide shortage in the cell.

PMID- 24906334
TI  - Imaging analysis to determine chromatin binding of the licensing factor MCM2-7 in
      mammalian cells.
AB  - S-CDK and DDK protein kinases initiate DNA replication at replication origins.
      Prior to the activation of these kinases, origins must become competent for
      replication by loading MCM2-7 DNA helicase on chromatin. This process is known as
      replication licensing or pre-replicative complex (pre-RC) formation. After the
      onset of S phase, however, licensing is inhibited to prevent re-replication of
      DNA. In this chapter, we describe a method to analyze origin licensing by imaging
      the chromatin-bound licensing factor MCM2-7. In a normal cell cycle, MCM2-7 is
      loaded at the end of mitosis or early G1 phase. As S phase progresses, MCM2-7 is
      dissociated from the replicated regions. When DNA replication is completed, cells
      in G2 phase have no chromatin-bound MCM2-7. The analysis of chromatin-bound MCM2
      7 in each cell provides an insight into cell cycle stage and condition for cell
      cycle. 

PMID- 24906335
TI  - Chromatin immunoprecipitation to investigate origin association of replication
      factors in mammalian cells.
AB  - A variety of DNA-binding proteins regulate DNA transactions including DNA
      replication and DNA damage response. To initiate DNA replication in S phase of
      the cell cycle, numerous replication proteins must be recruited to the
      replication origin in order to unwind and synthesize DNA. Some replication
      factors stay at the origin, while replisome components move with the replication
      fork. When the replisome encounters DNA damage or other issues during DNA
      replication, the replication fork stalls and accumulates single-stranded DNA that
      triggers the ATR-dependent replication checkpoint, in order to slow down S phase
      and arrest the cell cycle at the G2-M transition. It is also possible that
      replication forks collapse, leading to double-strand breaks that recruit various
      DNA damage response proteins to activate cell cycle checkpoints and DNA repair
      pathways. Therefore, defining the localization of DNA transaction factors during
      the cell cycle should provide important insights into mechanistic understanding
      of DNA replication and its related processes. In this chapter, we describe a
      chromatin immunoprecipitation method to locate replisome components at
      replication origins in human cells. 

PMID- 24906336
TI  - Live-cell fluorescence imaging for phenotypic analysis of mitosis.
AB  - Live-cell fluorescence microscopy is a powerful tool for characterizing aberrant
      mitotic phenotypes resulting from exposure to chemical inhibitors or after
      depletion of protein targets by RNA interference or other methods. Live imaging
      of cultured cells during mitotic progression presents challenges in maintaining
      optimal health of cells while achieving the temporal and spatial resolution to
      accomplish the goals of the study. We describe herein strategies to monitor and
      analyze mammalian cell mitosis with standard, inverted, fluorescence microscopy
      systems that are widely available. 

PMID- 24906337
TI  - Analyzing sister chromatid cohesion in mammalian cells.
AB  - The metaphase chromosome spread technique and subsequent analysis of sister
      chromatid cohesion is used for (clinical) diagnosis of genetic abnormalities that
      can cause aberrant sister chromatid cohesion. In addition, the technique can be
      used to assess the contribution of novel genes to the cohesion establishment and
      maintenance pathways. Cells are swelled in a hypotonic solution and fixed in
      Carnoy's solution. Samples are then dropped onto glass slides, and the spread
      chromosomes are stained and visualized by microscopy. Defects in sister chromatid
      cohesion can be easily assessed using this method, examples of which are given. 

PMID- 24906338
TI  - Affinity purification of protein complexes from Drosophila embryos in cell cycle
      studies.
AB  - The ability to identify protein interactions is key to elucidating the molecular
      mechanisms of cellular processes, including mitosis and cell cycle regulation.
      Drosophila melanogaster, as a model system, provides powerful tools to study cell
      division using genetics, microscopy, and RNAi. Drosophila early embryos are
      highly enriched in mitotic protein complexes as their nuclei undergo 13 rounds of
      rapid, synchronous mitotic nuclear divisions in a syncytium during the first 2 h
      of development. Here, we describe simple methods for the affinity purification of
      protein complexes from transgenic fly embryos via protein A- and green
      fluorescent protein-tags fused to bait proteins of interest. This in vivo
      proteomics approach has allowed the identification of several known and novel
      mitotic protein interactions using mass spectrometry, and it expands the use of
      the Drosophila model in modern molecular biology. 

PMID- 24906339
TI  - Tracking histone variant nucleosomes across the human cell cycle using
      biophysical, biochemical, and cytological analyses.
AB  - Histone variants such as H3.3, macroH2A, H2A.Z, and CENP-A are important
      epigenetic modifiers of the chromatin state in eukaryotic genomes. The
      centromeric histone H3 variant CENP-A/CENH3 epigenetically marks centromeres and
      is required for assembly of the kinetochore complex, a region of the chromosome
      that is responsible for proper genome segregation during mitosis. Several diverse
      techniques using biochemical, cell biology, and biophysical approaches have been
      utilized to study the nature of the CENP-A nucleosome across the cell cycle. In
      this chapter, we describe methods for CENP-A nucleosome purification and
      separation of CENP-A from other core histones using traditional SDS-PAGE and more
      resolving techniques such as Triton acid urea (TAU) and two-dimensional gels. We
      also discuss methods for observation of CENP-A on chromatin fibers using
      immunofluorescence. Finally, we provide a detailed description of analysis of
      chromatin structures using atomic force microscopy.

PMID- 24906340
TI  - [Dysphonia and dysphagia after anterior cervical spine surgery].
AB  - BACKGROUND: Anterior cervical spine surgery is a common procedure for fusions
      and/or discectomies. Postoperative dysphonia and dysphagia are known
      complications. In this study, we examined the frequency and outcomes of these
      complications in this patient population. MATERIALS AND METHODS: Patients planned
      to receive anterior cervical spine surgery between 01.03.2010 and 28.02.2011 at
      the Department of Neurosurgery, St. Gallen were prospectively included. Patients
      were evaluated using laryngoscopy, fiberoptic endoscopic evaluation of swallowing
      (FEES), voice field measurements and validated questionnaires. RESULTS: From the
      53 patients included in the study, 40 had at least one complete follow-up
      examination. The frequency of postoperative dysphonia due to recurrent nerve
      palsy was 4/40 (10 %), although this was temporary in 3 patients. FEES revealed a
      pathological result in 18.9 % of patients. Postoperative Swallowing Quality of
      Life Questionnaire (Swal-QoL) scores were significantly lower. CONCLUSION: At a
      frequency of 10 %, dysphonia due to recurrent nerve palsy is a relevant
      complication in cervical spine surgery, albeit temporary in most cases.
      Postoperative dysphagia is common and should be evaluated and treated during
      follow-up.

PMID- 24906341
TI  - Association between DNA repair genes (XPD and XRCC1) polymorphisms and
      susceptibility to age-related cataract (ARC): a meta-analysis.
AB  - BACKGROUND: DNA repair gene (XPD and XRCC1) polymorphisms have been considered as
      risk factors for the development of age-related cataract (ARC). To confirm the
      association between DNA repair gene (XPD and XRCC1) polymorphisms and the risk of
      ARC, a meta-analysis was conducted. METHODS: A search was made of published
      literature from Institute for Scientific Information (ISI) Web of Knowledge,
      PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI), and
      Wanfang Data. In addition, all studies evaluating the association between DNA
      repair genes (XPD and XRCC1) polymorphisms and the risk for ARC were included in
      our analysis. Pooled odds ratio (OR) and 95 % confidence interval (CI) were
      calculated by using fixed- or random-effects model. The Egger's test was used to
      check the publication bias. RESULTS: Six studies on XRCC1 Arg399Gln (1,300 cases,
      1,222 controls) and five studies on XPD Lys751Gln (1,092 cases, 1,061 controls)
      were included. For the XPD Lys751Gln (A/C) SNP, the overall analysis demonstrated
      that the CC genotype showed a significant association with a decreased risk for
      ARC compared with the AA genotype (OR = 0.59, 95 % CI, 0.38-0.92, P = 0.019).
      Similarly, the CC genotype showed a significant association with a decreased risk
      for ARC compared with the (AA + AC) genotype (OR = 0.65, 95 % CI, 0.43-0.98, P =
      0.040). Subgroup analysis showed that the association between the CC genotype and
      decreased risk for ARC is statistically significant in Caucasians (OR = 0.41, 95
      % CI, 0.24-0.73, P = 0.002) but not in Asians (OR = 1.06, 95 % CI, 0.51-2.19, P =
      0.877). For the XRCC1 Arg399Gln (G/A) SNP, the overall analysis demonstrated that
      the A allele showed a significant association with an increased risk for ARC
      compared with the G allele (OR = 1.16, 95 % CI, 1.03-1.31, P = 0.015). Subgroup
      analyses exhibited that the association between the A allele and the risk for ARC
      was statistically significant in Asians (OR = 1.23, 95 % CI, 1.07-1.41, P =
      0.003) but not in Caucasians (OR = 0.94, 95 % CI, 0.73-1.22, P = 0.660). Compared
      with the GG genotype, the GA genotype showed a significant association with an
      increased risk for ARC in Asians (OR = 1.32, 95 % CI, 1.08-1.61, P = 0.006) but
      not in Caucasians (OR = 0.58, 95 % CI, 0.27-1.26, P = 0.171). The Egger's test
      did not reveal an obvious publication bias among the included studies.
      CONCLUSIONS: Our meta-analysis suggested that the CC genotype of XPD Lys751Gln
      (A/C) SNP seemed to portend a decreased risk for ARC in Caucasian populations but
      not in Asian populations. The A allele and GA genotype of XRCC1 Arg399Gln (G/A)
      SNP might increase risk for ARC in Asian populations but not in Caucasian
      populations. More researches with larger and more different ethnic populations on
      this issue are therefore necessary.

PMID- 24906342
TI  - Evaluation of congenital excavated optic disc anomalies with spectral-domain and
      swept-source optical coherence tomography.
AB  - PURPOSE: To investigate the anatomic characteristics of congenital excavated
      optic disc anomalies by using fundus photography, spectral-domain optical
      coherence tomography (SD-OCT), and swept-source optical coherence tomography (SS
      OCT). METHODS: Fourteen eyes from 13 patients with congenital excavated optic
      disc anomalies underwent a complete ophthalmologic examination that included best
      corrected visual acuity evaluation, fundus photography, and SD-OCT. SS-OCT was
      performed in cases of peripapillary staphyloma cases in which the excavation
      depth could not be detected with SD-OCT. On the basis of the funduscopic and OCT
      findings, patients were classified as morning glory syndrome, optic disc
      coloboma, or peripapillary staphyloma. RESULTS: Seven eyes with morning glory
      syndrome were characterized by the presence of the preretinal tractional membrane
      in front of the excavated optic disc and could be divided into two groups: three
      eyes without retinal excavation, and four eyes with retinal excavation. Four eyes
      with optic disc coloboma showed inferiorly decentered scleral excavations with
      shallow optic disc excavation detectable by SD-OCT. Three eyes with peripapillary
      staphyloma showed deep excavation, the depth of which could not be detected by SD
      OCT. SS-OCT and enhanced depth imaging SD-OCT images focused on the bottom
      revealed membranous structure at the bottom of the excavation in two cases with
      peripapillary staphyloma. CONCLUSIONS: SD-OCT and SS-OCT are helpful for
      differential diagnosis of excavated optic disc anomalies. Morning glory syndrome,
      optic disc coloboma, and peripapillary staphyloma were respectively characterized
      by the presence of a preretinal tractional membrane, inferiorly decentered
      excavation, and an excavation deeper than that observed in morning glory syndrome
      and optic disc coloboma.

PMID- 24906343
TI  - Clinical predictors of radiographic abnormalities among infants with
      bronchiolitis in a paediatric emergency department.
AB  - BACKGROUND: Acute viral respiratory exacerbation is one of the most common
      conditions encountered in a paediatric emergency department (PED) during winter
      months. We aimed at defining clinical predictors of chest radiography
      prescription and radiographic abnormalities, among infants with bronchiolitis in
      a paediatric emergency department. METHODS: We conducted a prospective cohort
      study of children less than 2 years of age with clinical bronchiolitis, who
      presented for evaluation at the paediatric emergency department of an urban
      general hospital in France. Detailed information regarding historical features,
      examination findings, and management were collected. Clinical predictors of
      interest were explored in multivariate logistic regression models. RESULTS: Among
      410 chest radiographs blindly interpreted by two experts, 40 (9.7%) were
      considered as abnormal. Clinical predictors of chest radiography achievement were
      age (under three months), feeding difficulties, fever over 38 degrees C, hypoxia
      under than 95% of oxygen saturation, respiratory distress, crackles, and
      bronchitis rales. Clinical predictors of radiographic abnormalities were fever
      and close to significance hypoxia and conjunctivitis. CONCLUSION: Our study
      provides arguments for reducing chest radiographs in infants with bronchiolitis.
      For infants with clinical factors such as age less than three months, feeding
      difficulties, respiratory distress without hypoxia, isolated crackles or
      bronchitis rales, careful clinical follow-up should be provided instead of chest
      radiography.

PMID- 24906344
TI  - Augmented cellular trafficking and endosomal escape of porous silicon
      nanoparticles via zwitterionic bilayer polymer surface engineering.
AB  - The development of a stable vehicle with low toxicity, high cellular
      internalization, efficient endosomal escape, and optimal drug release profile is
      a key bottleneck in nanomedicine. To overcome all these problems, we have
      developed a successful layer-by-layer method to covalently conjugate
      polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA)
      copolymer on the surface of undecylenic acid functionalized thermally
      hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer
      zwitterionic nanocomposite containing free positive charge groups of hyper
      branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and
      hydrophilicity of the developed NPs considerably improved the colloidal and
      plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore,
      despite the surface negative charge of the bilayer polymer-conjugated NPs, the
      cellular trafficking and endosomal escape were significantly increased in both
      MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the
      conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P)
      NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the
      system and preserves the endosomal escape properties via proton sponge mechanism
      of the free available amine groups located inside the hyper-branched PEI layer.
      Moreover, the double layer protection not only controlled the aggregation of the
      NPs and reduced the toxicity, but also sustained the drug release of an
      anticancer drug, methotrexate, with further improved cytotoxicity profile of the
      drug-loaded particles. These results provide a proof-of-concept evidence that
      such zwitterionic polymer-based PSi nanocomposites can be extensively used as a
      promising candidate for cytosolic drug delivery. 

PMID- 24906346
TI  - The role of autophagy in the neurotoxicity of cationic PAMAM dendrimers.
AB  - Poly(amidoamine) (PAMAM) dendrimers, are among the most common classes of
      dendrimers that are intended for a wide range of biomedical applications and
      extensively investigated for brain-specific drug delivery, imaging and diagnosis.
      Unfortunately, neurotoxicity of PAMAM dendrimers, the underlying mechanism of
      which is poorly-elucidated, poses a far-reaching challenge to their practical
      applications. In this study, we reported that PAMAM dendrimers induced both
      cytotoxicity and autophagic flux in a panel of human glioma cell lines.
      Meanwhile, inhibition of autophagy significantly reversed cell death caused by
      PAMAM dendrimers, indicating the cytotoxic role of autophagy in neurotoxicity
      caused by PAMAM dendrimers. Akt/mTOR pathway was most likely to participate in
      initiation of PAMAM dendrimers-induced autophagy. Moreover, autophagy induced by
      PAMAM dendrimers might be partially mediated by intracellular ROS generation.
      Collectively, these data elucidated the critical role of autophagy in
      neurotoxicity associated with exposure to cationic PAMAM dendrimers in vitro,
      raising concerns about possible neurotoxic reaction caused by future clinical
      applications of PAMAM dendrimers and providing potential strategies to ameliorate
      toxic effects of PAMAM dendrimers. 

PMID- 24906347
TI  - Oral zinc and common childhood infections--An update.
AB  - Zinc is an essential micronutrient important for growth and for normal function
      of the immune system. Many children in developing countries have inadequate zinc
      nutrition. Routine zinc supplementation reduces the risk of respiratory
      infections and diarrhea, the two leading causes of morbidity and mortality in
      young children worldwide. In childhood diarrhea oral zinc also reduces illness
      duration and risk of persistent episodes. Oral zinc is therefore recommended for
      the treatment of acute diarrhea in young children. The results from the studies
      that have measured the therapeutic effect of zinc on acute respiratory
      infections, however, are conflicting. Moreover, the results of therapeutic zinc
      for childhood malaria also are so far not promising.This paper gives a brief
      outline of the current evidence from clinical trials on therapeutic effect of
      oral zinc on childhood respiratory infections, pneumonia and malaria and also of
      new evidence of the effect on serious bacterial illness in young infants. 

PMID- 24906348
TI  - Burn care in South Africa: a micro cosmos of Africa.
AB  - Burn injuries in Africa are common with between 300,000 and 17.5 million children
      under 5 years sustaining burn injuries annually, resulting in a high estimated
      fatality rate. These burns are largely environmentally conditioned and therefore
      preventable. The Western Cape Province in South Africa can be regarded as a
      prototype of paediatric burns seen on the continent, with large numbers, high
      morbidity and mortality rates and an area inclusive of all factors contributing
      to this extraordinary burden of injury. Most of the mechanisms to prevent burns
      are not easily modified due to the restraint of low socio-economic homes,
      overcrowding, unsafe appliances, multiple and complex daily demands on families
      and multiple psycho-social stressors. Children <4 years are at highest risk of
      burns with an average annual rate of 6.0/10,000 child-years. Burn care in South
      Africa is predominantly emergency driven and variable in terms of organization,
      clinical management, facilities and staffing. Various treatment strategies were
      introduced. The management of HIV positive children poses a problem, as well as
      the conflict of achieving equity of burn care for all children. Without
      alleviating poverty, developing minimum standards for housing, burn education,
      safe appliances and legislation, we will not be able to reduce the "curse of poor
      people" and will continue to treat the consequences.

PMID- 24906345
TI  - Microfluidic techniques for development of 3D vascularized tissue.
AB  - Development of a vascularized tissue is one of the key challenges for the
      successful clinical application of tissue engineered constructs. Despite the
      significant efforts over the last few decades, establishing a gold standard to
      develop three dimensional (3D) vascularized tissues has still remained far from
      reality. Recent advances in the application of microfluidic platforms to the
      field of tissue engineering have greatly accelerated the progress toward the
      development of viable vascularized tissue constructs. Numerous techniques have
      emerged to induce the formation of vascular structure within tissues which can be
      broadly classified into two distinct categories, namely (1) prevascularization
      based techniques and (2) vasculogenesis and angiogenesis-based techniques. This
      review presents an overview of the recent advancements in the vascularization
      techniques using both approaches for generating 3D vascular structure on
      microfluidic platforms. 

PMID- 24906349
TI  - Polymorphisms at the 3' untranslated region of SLC11A1 gene are associated with
      protection to Brucella infection in goats.
AB  - Goats are susceptible to brucellosis and the detection of Brucella-infected
      animals is carried out by serological tests. In other ruminant species,
      polymorphisms in microsatellites (Ms) of 3' untranslated region (3'UTR) of the
      solute carrier family 11 member A1 (SLC11A1) gene were associated with resistance
      to Brucella abortus infection. Goats present two polymorphic Ms at the 3'UTR end
      of SLC11A1 gene, called regions A and B. Here, we evaluated if polymorphisms in
      regions A and/or B are associated with Brucella infection in goats. Serum (for
      the detection of Brucella-specific antibodies) and hair samples (for DNA
      isolation and structure analysis of the SLC11A1 gene) were randomly collected
      from 229 adult native goats from the northwest of Argentina. Serological status
      was evaluated by buffer plate antigen test (BPAT) complemented by the fluorescent
      polarization assay (FPA), and the genotype of the 3'UTR of the SLC11A1 gene was
      determined by capillary electrophoresis and confirmed by sequence analysis.
      Polymorphisms in regions A and B of the 3'UTR SLC11A1 gene were found
      statistically significant associated with protection to Brucella infection.
      Specifically, the association study indicates statistical significance of the
      allele A15 and B7/B7 genotype with absence of Brucella-specific antibodies
      (p=0.0003 and 0.0088, respectively). These data open a promising opportunity for
      limiting goat brucellosis through selective breeding of animals based on genetic
      markers associated with natural resistance to B. melitensis infection.

PMID- 24906350
TI  - Effect of continuous milking on immunoglobulin concentrations in bovine
      colostrum.
AB  - Continuous milking is defined as a dairy cattle management system without a
      planned dry period for cows in late gestation. Continuous milking has been
      described to reduce health problems common in periparturient cattle, but may
      affect colostrum immunoglobulin (Ig) concentration and subsequently calf health.
      This study reports the influence of continuous milking on Ig concentrations of
      bovine colostrum in commercial dairy farms. Colostrum Ig concentrations of 227
      cows from 13 herds were quantified with a quantitative ELISA for IgG, IgG1, IgG2,
      IgA and IgM. Colostrum samples of continuous milked (CM) cows (n=38) were
      compared with colostrum samples of cows (n=189) after a traditional dry period
      (DP) of at least 42 days. RESULTS: indicated that colostrum Ig concentration was
      significantly lower in continuous milking systems where IgG, IgG1, IgG2, IgA and
      IgM concentrations were reduced by half compared with cows that had a planned dry
      period. When relating the results from this study to recommendations for
      colostrum management it can be concluded that although colostrum Ig
      concentrations are significantly lower in a continuous milking management system
      an adequate passive immune transfer can still be achieved based on colostrum
      quality provided colostrum feeding management is optimal.

PMID- 24906351
TI  - Managing HIV and Hodgkin lymphoma in the twenty-first century.
AB  - Hodgkin lymphoma (HL) is more frequent in patients with Human Immunodeficiency
      Virus (HIV) infection than in immunocompetent patients. The relationship between
      the immune system and HL is complex. Whilst the incidence of HL in HIV patients
      has most likely increased since the introduction of combined anti-retroviral
      therapy (cART), there is no doubt that the outcomes for patients with HIV and HL
      (HIV-HL) have improved since its introduction. Improved CD4 counts and risk
      adapted treatment schedules have resulted in outcomes for patients with HIV-HL
      that are comparable to those in HIV-negative patients with HL. Thus, HIV-HL
      should be treated in the same way as HL in immunocompetent patients, including
      the use of salvage chemotherapy and autologous transplant in the relapsed setting
      in HIV-HL. Along the same lines, patients with HIV-HL should not be excluded from
      trials based on their immune status alone. 

PMID- 24906352
TI  - Intralesional treatment of stage III metastatic melanoma patients with L19-IL2
      results in sustained clinical and systemic immunologic responses.
AB  - L19-IL2 is a recombinant protein comprising the cytokine IL2 fused to the single
      chain monoclonal antibody L19. In previous studies, intralesional injection with
      IL2 has shown efficacy for the locoregional treatment of cutaneous/subcutaneous
      metastases in patients with advanced melanoma. The objectives of this study were
      to investigate whether (i) intralesional delivery of a targeted form of IL2 would
      yield similar results, with reduction of injection frequency and treatment
      duration; and (ii) systemic immune responses were induced by the local treatment.
      Patients with stage IIIB/IIIC melanoma and cutaneous/subcutaneous injectable
      metastases received weekly intratumoral injections of L19-IL2 at a maximum dose
      of 10 MIU/week for 4 consecutive weeks. Tumor response was evaluated 12 weeks
      after the first treatment. Twenty-four of 25 patients were evaluable for therapy
      induced responses. A complete response (CR) by modified immune-related response
      criteria (irRC) of all treated metastases was achieved in 6 patients (25%), with
      long-lasting responses in most cases (5 patients for >=24 months). Objective
      responses were documented in 53.9% of all index lesions [44.4% CR and 9.5%
      partial responses (by irRC)], and 36.5% of these remained stable, while 9.5%
      progressed. Toxicity was comparable with that of free IL2, and no serious adverse
      events were recorded. A significant temporary increase of peripheral regulatory T
      cells and natural killer cells, sustained increase of absolute CD4(+)
      lymphocytes, and decrease of myeloid-derived suppressor cells were observed upon
      treatment. Finally, we recorded encouraging data about the progression time to
      distant metastases and overall survival.

PMID- 24906353
TI  - How to manage the chronic pelvic pain syndrome in men presenting to sexual health
      services.

PMID- 24906354
TI  - Anal cancer rates quadruple among UK women in past 40 years.

PMID- 24906355
TI  - Polyamine Oxidase5 Regulates Arabidopsis Growth through Thermospermine Oxidase
      Activity.
AB  - The major plant polyamines (PAs) are the tetraamines spermine (Spm) and
      thermospermine (T-Spm), the triamine spermidine, and the diamine putrescine. PA
      homeostasis is governed by the balance between biosynthesis and catabolism; the
      latter is catalyzed by polyamine oxidase (PAO). Arabidopsis (Arabidopsis
      thaliana) has five PAO genes, AtPAO1 to AtPAO5, and all encoded proteins have
      been biochemically characterized. All AtPAO enzymes function in the back
      conversion of tetraamine to triamine and/or triamine to diamine, albeit with
      different PA specificities. Here, we demonstrate that AtPAO5 loss-of-function
      mutants (pao5) contain 2-fold higher T-Spm levels and exhibit delayed transition
      from vegetative to reproductive growth compared with that of wild-type plants.
      Although the wild type and pao5 are indistinguishable at the early seedling
      stage, externally supplied low-dose T-Spm, but not other PAs, inhibits aerial
      growth of pao5 mutants in a dose-dependent manner. Introduction of wild-type
      AtPAO5 into pao5 mutants rescues growth and reduces the T-Spm content,
      demonstrating that AtPAO5 is a T-Spm oxidase. Recombinant AtPAO5 catalyzes the
      conversion of T-Spm and Spm to triamine spermidine in vitro. AtPAO5 specificity
      for T-Spm in planta may be explained by coexpression with T-Spm synthase but not
      with Spm synthase. The pao5 mutant lacking T-Spm oxidation and the acl5 mutant
      lacking T-Spm synthesis both exhibit growth defects. This study indicates a
      crucial role for T-Spm in plant growth and development.

PMID- 24906356
TI  - Coronary artery disease detected by coronary computed tomographic angiography is
      associated with intensification of preventive medical therapy and lower low
      density lipoprotein cholesterol.
AB  - BACKGROUND: Coronary computed tomographic angiography (CCTA) is an accurate test
      for the identification of coronary artery disease (CAD), yet the impact of CCTA
      results on subsequent medical therapy and risk factors has not been widely
      reported. METHODS AND RESULTS: We identified consecutive patients aged >18 years
      without prior CAD who underwent CCTA from 2004 to 2011 and had complete data on
      medications before and after CCTA. CCTA results were categorized as no CAD, <50%
      stenosis, and >=50% stenosis. Based on the number of involved segments, extent of
      disease was categorized as nonextensive (<=4 segments) or extensive CAD (>4
      segments). Electronic medical records and patient interviews were reviewed
      blinded to CCTA findings to assess initiation of aspirin and intensification of
      lipid-lowering therapies. Survival analysis was performed to evaluate
      intensification of lipid therapy as a predictor of cardiovascular death or
      nonfatal myocardial infarction. Among 2839 patients with mean follow-up of 3.6
      years, the odds of physician intensification of lipid-lowering therapy
      significantly increased for those with nonobstructive CAD (odds ratio, 3.6; 95%
      confidence interval, 2.9-4.9; P<0.001) and obstructive CAD (odds ratio, 5.6; 95%
      confidence interval, 4.3-7.3; P<0.001). Low-density lipoprotein cholesterol
      levels declined significantly in association with intensification of lipid
      lowering therapy after CCTA in all patient subgroups. In a hypothesis-generating
      analysis, among patients with nonobstructive but extensive CAD, statin use after
      CCTA was associated with a reduction in cardiovascular death or myocardial
      infarction (hazards ratio, 0.18; 95% confidence interval, 0.05-0.66; P=0.01).
      CONCLUSIONS: Abnormal CCTA findings are associated with downstream
      intensification in statin and aspirin therapy. In particular, CCTA may lead to
      increased use of prognostically beneficial therapies in patients identified as
      having extensive, nonobstructive CAD.

PMID- 24906357
TI  - Systemic exposure to PAHs and benzene in firefighters suppressing controlled
      structure fires.
AB  - Turnout gear provides protection against dermal exposure to contaminants during
      firefighting; however, the level of protection is unknown. We explored the dermal
      contribution to the systemic dose of polycyclic aromatic hydrocarbons (PAHs) and
      other aromatic hydrocarbons in firefighters during suppression and overhaul of
      controlled structure burns. The study was organized into two rounds, three
      controlled burns per round, and five firefighters per burn. The firefighters wore
      new or laundered turnout gear tested before each burn to ensure lack of PAH
      contamination. To ensure that any increase in systemic PAH levels after the burn
      was the result of dermal rather than inhalation exposure, the firefighters did
      not remove their self-contained breathing apparatus until overhaul was completed
      and they were >30 m upwind from the burn structure. Specimens were collected
      before and at intervals after the burn for biomarker analysis. Urine was analyzed
      for phenanthrene equivalents using enzyme-linked immunosorbent assay and a
      benzene metabolite (s-phenylmercapturic acid) using liquid chromatography/tandem
      mass spectrometry; both were adjusted by creatinine. Exhaled breath collected on
      thermal desorption tubes was analyzed for PAHs and other aromatic hydrocarbons
      using gas chromatography/mass spectrometry. We collected personal air samples
      during the burn and skin wipe samples (corn oil medium) on several body sites
      before and after the burn. The air and wipe samples were analyzed for PAHs using
      a liquid chromatography with photodiode array detection. We explored possible
      changes in external exposures or biomarkers over time and the relationships
      between these variables using non-parametric sign tests and Spearman tests,
      respectively. We found significantly elevated (P < 0.05) post-exposure breath
      concentrations of benzene compared with pre-exposure concentrations for both
      rounds. We also found significantly elevated post-exposure levels of PAHs on the
      neck compared with pre-exposure levels for round 1. We found statistically
      significant positive correlations between external exposures (i.e. personal air
      concentrations of PAHs) and biomarkers (i.e. change in urinary PAH metabolite
      levels in round 1 and change in breath concentrations of benzene in round 2). The
      results suggest that firefighters wearing full protective ensembles absorbed
      combustion products into their bodies. The PAHs most likely entered firefighters'
      bodies through their skin, with the neck being the primary site of exposure and
      absorption due to the lower level of dermal protection afforded by hoods.
      Aromatic hydrocarbons could have been absorbed dermally during firefighting or
      inhaled during the doffing of gear that was off-gassing contaminants. 

PMID- 24906359
TI  - Nutritional reformulation: Fortification in the factory and in the field.
AB  - Deficiencies in DHA/EPA are widespread, but not widely recognised. The scale of
      the problem is difficult to assess, because targets for consumption vary and
      intakes are poorly measured, but most people in most countries eat too little.
      The principal policies to correct the shortfalls have been educational programmes
      urging people to eat more fish. Two problems limit this approach: many do not
      like fish; and there are not enough fish available if everyone ate recommended
      levels. One pragmatic alternative is to start with the popular foods people
      actually eat, then fortify them with DHA/EPA. The paper discusses technical
      options for doing this, and three problems: the scale of sales, the use of
      inappropriate forticants, and the costs. The key to reducing costs lies in
      obtaining new, larger, sustainable and cheaper sources of DHA/EPA. Major efforts
      to achieve this are underway the genetically modified crops and new sources of
      algae. The public health goal is affordable fortified foods consumed by billions,
      not just affluent, health-conscious minorities. It is a strategy for nutritional
      improvement without dietary change.

PMID- 24906358
TI  - A new clinical cut-off of cytokeratin 19 mRNA copy number in sentinel lymph node
      better identifies patients eligible for axillary lymph node dissection in breast
      cancer.
AB  - AIMS: Cytokeratin 19 (CK19) mRNA copy number predicts the probability of tumour
      load in axillary lymph nodes (ALN) and can help in decision-making regarding the
      axillary dissection. The purpose of this study was to define a new cut-off of
      CK19 mRNA copy number using the one-step nucleic acid amplification (OSNA) assay
      on metastatic sentinel lymph nodes (SLN) in order to identify cases at risk of
      having one or more positive ALN. METHODS: 1296 SLN from 1080 patients were
      analysed with the OSNA assay. 194 patients with positive SLN underwent ALN
      dissection and the mean value of CK19 copy number (320 000) of their SLN was set
      as initial cut-off. Receiver operative characteristics curve identify a best cut
      off of 7700 (sensitivity 78%, specificity 57%). A comparison between our and the
      traditional cut-off (5000) was performed. RESULTS: The cut-off of 7700
      successfully identifies patients with positive ALN (p=0.001, false- negative
      cases: 17%). In the range between 5000 and 7700, one patient with positive ALN
      would not undergo axillary dissection, whereas eight patients with negative ALN
      would be correctly identified. CONCLUSIONS: We suggest that the level of CK19
      mRNA copy number could be the only parameter to consider in the intraoperative
      management of the axilla.

PMID- 24906360
TI  - Predictors of Maternal Parental Self-Efficacy Among Primiparas in the Early
      Postnatal Period.
AB  - Maternal parental self-efficacy is a crucial factor for facilitating the smooth
      transition into motherhood, particularly for primiparas. The aims of this study
      were to examine the predictors of maternal parental self-efficacy and its
      relationship with social support, postnatal depression (PND), and socio
      demographic variables of primiparas during the early postnatal period. A
      descriptive correlational study design was adopted. The instruments, Perceived
      Maternal Parental Self-Efficacy, Perinatal Infant Care Social Support, and
      Edinburgh Postnatal Depression Scale, were used to collect data from a purposive
      sample of 122 primiparas on the day of discharge (1-3 days post delivery) in a
      tertiary public hospital in Singapore. There were significant correlations among
      maternal parental self-efficacy, social support, and postnatal depression. The
      main predictors of maternal parental self-efficacy were social support,
      ethnicity, maternal age, and family income. The maternal parental self-efficacy,
      social support, and PND should be routinely assessed to provide necessary support
      to needy mothers. 

PMID- 24906361
TI  - Automation of serum (1->3)-beta-D-glucan testing allows reliable and rapid
      discrimination of patients with and without candidemia.
AB  - Testing for (1->3)-beta-D-glucan (BDG) is used for detection of invasive fungal
      infection. However, current assays lack automation and the ability to conduct
      rapid single-sample testing. The Fungitell assay was adopted for automation and
      evaluated using clinical samples from patients with culture-proven candidemia and
      from culture-negative controls in duplicate. A comparison with the standard assay
      protocol was made in order to establish analytical specifications. With the
      automated protocol, the analytical measuring range was 8-2500 pg/ml of BDG, and
      precision testing resulted in coefficients of variation that ranged from 3.0% to
      5.5%. Samples from 15 patients with culture-proven candidemia and 94 culture
      negative samples were evaluated. All culture-proven samples showed BDG values >80
      pg/ml (mean 1247 pg/ml; range, 116-2990 pg/ml), which were considered positive.
      Of the 94 culture-negative samples, 92 had BDG values <60 pg/ml (mean, 28 pg/ml),
      which were considered to be negative, and 2 samples were false-positive (>=80
      pg/ml; up to 124 pg/ml). Results could be obtained within 45 min and showed
      excellent agreement with results obtained with the standard assay protocol. The
      automated Fungitell assay proved to be reliable and rapid for diagnosis of
      candidemia. It was demonstrated to be feasible and cost efficient for both single
      sample and large-scale testing of serum BDG. Its 1-h time-to-result will allow
      better support for clinicians in the management of antifungal therapy. 

PMID- 24906363
TI  - Victim Age and the Generalist Versus Specialist Distinction in Adolescent Sexual
      Offending.
AB  - More knowledge is needed about the etiology and treatment needs of adolescent sex
      offenders. The current study compared adolescents who had offended against
      children (defined as below the age of 12 and at least 5 years younger than the
      adolescent), adolescents who have offended against peers or adults, and
      adolescents who had victims in both age groups. Based on Seto and Lalumiere's
      meta-analytic findings, participants were compared on theoretically derived
      factors, including childhood sexual abuse, atypical sexual interests, sexual
      experience, social competence, psychiatric history, and general delinquency
      factors (past criminal history, substance abuse history, and offense
      characteristics). The study sample consisted of 162 court-referred male
      adolescent sexual offenders aged 12 to 17 years. Of the six identified domains,
      groups significantly differed on five of them; the exceptions were variables
      reflecting social competence. The results further support the validity of
      distinguishing adolescent sex offenders by victim age.

PMID- 24906362
TI  - Determinants of HIV testing among Nigerian couples: a multilevel modelling
      approach.
AB  - In this article we analyse the determinants of HIV testing among Nigerian couples
      using Demographic and Health Survey data set (2008). This study is motivated by
      the fact that although there is a strong willingness from the Nigerian Government
      to examine new HIV preventions approaches such as Pre-Exposure Prophylaxis for
      HIV (PrEP) and Treatment as Prevention (TasP) for HIV serodiscordant couples, the
      implementation of such policies would require the HIV status of each partner in
      the couple to be known. This is far to be achieved in the Nigerian context since
      in Nigeria only 6% of couples know their HIV status. In order to identify
      potential policies that are needed to increase HIV testing uptake, we use a three
      level random intercept logistic model to separately explore the determinants of
      knowing HIV status among female and male partners. The use of the multilevel
      modelling allows including the unobserved heterogeneity at the village and state
      level that may affect HIV testing behaviours. Our results indicate that
      education, wealth, stigma, HIV knowledge and perceived risk are predictors of HIV
      testing among both partners while routine provider initiated testing appears to
      be very effective to increase HIV testing among women. The introduction of
      financial incentives as well as an increase in routine testing and home-based
      testing may be needed for large scale increase in HIV testing prior to the
      implementation of new HIV prevention technologies among discordant couples. 

PMID- 24906364
TI  - Helping Sex Offenders to Desist Offending: The Gains and Drains for CoSA
      Volunteers-A Review of the Literature.
AB  - In Circles of Support and Accountability (CoSA), a group of trained volunteers
      support sex offenders in their desistance process by engaging in a long-lasting
      empathic relationship. Is it safe to employ volunteers in this way? This
      literature review provides an overview of both theoretical explanations and
      empirical evidence of the possible impact of this type of volunteerism on the
      volunteers themselves. Fifty original research articles and reviews met the
      selection criteria of a systematic search. Results on effects of volunteering in
      general, effects of volunteer work with offenders, and effects of working with
      sex offenders on professionals are summarized and integrated. Generally,
      volunteering supports and improves physical health and mental well-being,
      personal growth, and citizenship. However, working with sex offenders in an
      empathic relationship generates both positive and negative effects on
      psychological and social function. Personal characteristics, task
      characteristics, and organizational characteristics moderate and mediate the
      impact. 

PMID- 24906366
TI  - Systemic inflammation and imbalance between endothelial injury and repair in
      patients with psoriasis are associated with preclinical atherosclerosis.
AB  - BACKGROUND: Systemic inflammation and imbalance between endothelial injury and
      repair, the latter referred to as vascular incompetence, are associated with
      atherosclerosis and cardiovascular risk. Psoriasis, an inflammatory disease of
      the skin, has been associated with atherosclerosis. We investigated whether, in
      psoriasis, inflammation and vascular incompetence are associated with carotid
      intima-media thickness (cIMT) irrespective of metabolic syndrome and other
      established cardiovascular risk factors. METHODS: High sensitivity C-reactive
      protein (hsCRP), the ratio between endothelial microparticles (EMPs) and
      progenitors (EPCs), a marker of vascular incompetence, and cIMT were measured in
      84 patients with psoriasis and 90 healthy controls, balanced for age, gender and
      the prevalence of metabolic syndrome. RESULTS: Patients with psoriasis had higher
      hsCRP, EMP/EPC ratio and cIMT than controls. Patients with both psoriasis and
      metabolic syndrome had the highest hsCRP levels, psoriasis and metabolic syndrome
      being associated with a 3.1- and 2.6-fold increased risk of having high hsCRP
      levels, respectively. Logarithm transformed hsCRP and EMP/EPC ratio were
      predictors of high cIMT (odds ratio 3.8; 95% confidence interval 1.3-11.4; p =
      0.02 and odds ratio 8.7; 95% confidence interval 2.7-27.5; p < 0.001,
      respectively) regardless of confounders. Patients with high hsCRP and EMP/EPC
      ratio had higher cIMT than those with none or at least one of risk variable.
      CONCLUSIONS: Patients with psoriasis have an increased burden of cardiovascular
      risk, including inflammation, vascular incompetence and early atherosclerosis.
      Increased hsCRP levels, possibly sustained by the inflammatory nature of
      psoriasis and metabolic syndrome, and vascular incompetence are associated with
      early carotid atherosclerosis, regardless of metabolic syndrome and other
      established cardiovascular risk factors.

PMID- 24906365
TI  - MR-proANP improves prediction of mortality and cardiovascular events in patients
      with STEMI.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) is released from the atria (on
      cleavage of proANP) in response to elevated intra-atrial pressure and wall
      stretch. Clinical data on proANP are still limited, mainly due to limitations in
      assaying the protein, which recently have been solved. ProANP is elevated in
      cardiovascular disease and predicts outcome in heart failure. However, knowledge
      of the prognostic value in acute myocardial infarction remains limited. METHODS:
      We prospectively included 680 patients with STEMI treated with primary-PCI, from
      September 2006 to December 2008. Blood samples were drawn immediately before PCI.
      Plasma MR-proANP was measured using an automated processing assay. Endpoints were
      all-cause mortality (n = 137) and the combined endpoint (n = 170) of major
      adverse cardiovascular events (MACE) defined as cardiovascular mortality and
      admission due to recurrent MI, ischaemic stroke or heart failure. RESULTS: During
      5-year follow-up, MR-proANP was associated with increased risk of all-cause
      mortality and MACE (both p < 0.001). After adjustment for confounding risk
      factors (age, gender, hypertension, diabetes, hypercholesterolaemia, smoking,
      previous MI, BMI, eGFR, CRP, peak-TnI, symptom-to-balloon time, multivessel
      disease, complex lesion, LAD-lesion and use of glycoprotein inhibitor), MR-proANP
      remained an independent predictor of all-cause mortality and MACE - hazard ratio:
      1.68 (95% CI 1.35-2.10; p < 0.001) and 1.68 (95% CI 1.39-2.03; p < 0.001) per
      standard deviation increase in MR-proANP. MR-proANP significantly increased C
      statistics and reclassified 26% of the patients for all-cause mortality and 34%
      for MACE into higher or lower risk categories, matching actual event rates more
      accurately. CONCLUSIONS: Plasma MR-proANP independently predicts all-cause
      mortality and MACE in patients with STEMI.

PMID- 24906367
TI  - Cohort Profile: The Danish Conscription Database(DCD): A cohort of 728,160 men
      born from 1939 through 1959.
AB  - The Danish Conscription Database (DCD) was established to enable studies of the
      influence of early physical and mental exposures on adverse health and social
      outcomes from a life-course perspective. In Denmark, all young men are requested
      to appear before the conscription board when they turn 18 years, to be assessed
      for military service. The DCD was established by digitizing information from
      conscription board register cards on the height, weight, educational level,
      intelligence test score and examination details of Danish conscripts. The DCD
      contains information on 728,160 men born from 1939 through 1959 and examined by
      the conscription board from 1957 through 1984. The unique Danish personal
      identification number of each individual conscript has been traced, and this
      allows linkage of the DCD to all Danish health and socioeconomic registers. More
      than 130,000 deaths have been identified in a recent linkage to the Danish
      Register of Cause of Death. We encourage collaboration, and interested
      researchers should contact: danishconscriptiondatabase.glostrup
      hospital@regionh.dk.

PMID- 24906368
TI  - High tobacco consumption is causally associated with increased all-cause
      mortality in a general population sample of 55,568 individuals, but not with
      short telomeres: a Mendelian randomization study.
AB  - BACKGROUND: High cumulative tobacco consumption is associated with short
      telomeres and with increased all-cause mortality. We tested the hypothesis that
      high tobacco consumption is causally associated with short telomeres and with
      increased all-cause mortality. METHODS: We studied 55,568 individuals including
      32,823 ever smokers from the Danish general population, of whom 3430 died during
      10 years of follow-up. All had telomere length measured, detailed information on
      smoking history, and CHRNA3 rs1051730 genotype, which is associated with tobacco
      consumption, determined. In a Mendelian randomization study, we conducted
      observational, genetic, and mediation analyses. RESULTS: First, tobacco
      consumption was 21.1 pack-years in non-carriers, 22.8 in heterozygotes and 24.8
      in homozygotes (P-trend<0.001). Second, the observational multivariable adjusted
      hazard ratio for all-cause mortality was 1.12 [95% confidence interval (CI):
      1.09, 1.15] per doubling in tobacco consumption. In Mendelian randomization
      analysis, the hazard ratio was 1.08 (1.02, 1.14) per minor CHRNA3 allele in ever
      smokers. Third, in observational analysis telomeres shortened with -13 base pairs
      (-18, -8) per doubling in tobacco consumption. In Mendelian randomization
      analysis, the estimate was +3 base pairs (-10, +15) per minor CHRNA3 allele.
      Finally, individuals with the shortest vs longest telomeres had a multivariable
      adjusted hazard ratio of 1.30 (1.13, 1.50) for all-cause mortality; however, in
      mediation analysis short telomeres explained only +0.4% (-3.5%, +4.3%) of the
      association between high tobacco consumption and increased all-cause mortality.
      CONCLUSIONS: High tobacco consumption is causally associated with increased all
      cause mortality. High cumulative tobacco consumption is associated with short
      telomeres observationally, but there is no clear genetic association.

PMID- 24906369
TI  - Dabigatran etexilate and risk of myocardial infarction, other cardiovascular
      events, major bleeding, and all-cause mortality: a systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Signals of an increased risk of myocardial infarction (MI) have been
      identified with dabigatran etexilate in randomized controlled trials (RCTs).
      METHODS AND RESULES: We conducted searches of the published literature and a
      clinical trials registry maintained by the drug manufacturer. Criteria for
      inclusion in our meta-analysis included all RCTs and the availability of outcome
      data for MI, other cardiovascular events, major bleeding, and all-cause
      mortality. Among the 501 unique references identified, 14 RCTs fulfilled the
      inclusion criteria. Stratification analyses by comparators and doses of
      dabigatran etexilate were conducted. Peto odds ratio (ORPETO) values using the
      fixed-effect model (FEM) for MI, other cardiovascular events, major bleeding, and
      all-cause mortality were 1.34 (95% CI 1.08 to 1.65, P=0.007), 0.93 (95%CI 0.83 to
      1.06, P=0.270), 0.88 (95% CI 0.79 to 0.99, P=0.029), and 0.89 (95% CI 0.80 to
      1.00, P=0.041). When compared with warfarin, ORPETO values using FEM were 1.41
      (95% CI 1.11 to 1.80, P=0.005), 0.94 (95%CI 0.83 to 1.06, P=0.293), 0.85 (95% CI
      0.76 to 0.96, P=0.007), and 0.90 (95% CI 0.81 to 1.01, P=0.061), respectively. In
      RCTs using the 150-mg BID dosage, the ORPETO values using FEM were 1.45 (95% CI
      1.11 to 1.91, P=0.007), 0.95 (95% CI 0.82 to 1.09, P=0.423), 0.92 (95% CI 0.81 to
      1.05, P=0.228), and 0.88 (95% CI 0.78 to 1.00, P=0.045), respectively. The
      results of the 110-mg BID dosage were mainly driven by the RE-LY trial.
      CONCLUSIONS: This meta-analysis provides evidence that dabigatran etexilate is
      associated with a significantly increased risk of MI. This increased risk should
      be considered taking into account the overall benefit in terms of major bleeding
      and all-cause mortality.

PMID- 24906370
TI  - Assessment of a University of California, Los Angeles 4-variable risk score for
      advanced heart failure.
AB  - BACKGROUND: The 4-variable risk score from University of California, Los Angeles
      (UCLA) demonstrated superior discrimination in advanced heart failure, compared
      to established risk scores. However, the model has not been externally validated,
      and its suitability as a selection tool for heart transplantation (HT) and left
      ventricular assist device (LVAD) is unknown. METHODS AND RESULTS: We calculated
      the UCLA risk score (based on B-type natriuretic peptide, peak VO2, New York
      Heart Association class, and use of angiotensin-converting enzyme inhibitor or
      angiotensin receptor blocker) in 180 patients referred for HT. The outcome was
      survival free from urgent transplantation or LVAD. The model-predicted survival
      was compared to Kaplan-Meier's estimated survival at 1, 2, and 3 years. Model
      discrimination and calibration were assessed. During a mean follow-up of 2.1
      years, 37 (21%) events occurred. One-, 2- and 3-year observed event-free survival
      was 88%, 81%, and 75%, and the observed/predicted ratio was 0.97, 0.96, and 0.97,
      respectively. Time-dependent receiver operating characteristic curve analyses
      demonstrated good discrimination overall (1-year area under curve, 0.801; 2-year,
      0.774; 3-year, 0.837), but discrimination between the 2 highest risk groups was
      poor. The difference between observed and predicted survival ranged from -14 to
      +17 percentage points, suggesting poor model calibration. Fairly similar results
      were found when the analyses were repeated in 715 patients after multivariate
      imputation of missing data. CONCLUSIONS: The UCLA 4-variable risk model
      calibration was inconsistent and high-risk discrimination was poor in an external
      validation cohort. Further model assessment is warranted before widespread use.

PMID- 24906371
TI  - Zebrafish enpp1 mutants exhibit pathological mineralization, mimicking features
      of generalized arterial calcification of infancy (GACI) and pseudoxanthoma
      elasticum (PXE).
AB  - In recent years it has become clear that, mechanistically, biomineralization is a
      process that has to be actively inhibited as a default state. This inhibition
      must be released in a rigidly controlled manner in order for mineralization to
      occur in skeletal elements and teeth. A central aspect of this concept is the
      tightly controlled balance between phosphate, a constituent of the biomineral
      hydroxyapatite, and pyrophosphate, a physiochemical inhibitor of mineralization.
      Here, we provide a detailed analysis of a zebrafish mutant, dragonfish (dgf),
      which is mutant for ectonucleoside pyrophosphatase/phosphodiesterase 1 (Enpp1), a
      protein that is crucial for supplying extracellular pyrophosphate. Generalized
      arterial calcification of infancy (GACI) is a fatal human disease, and the
      majority of cases are thought to be caused by mutations in ENPP1. Furthermore,
      some cases of pseudoxanthoma elasticum (PXE) have recently been linked to ENPP1.
      Similar to humans, we show here that zebrafish enpp1 mutants can develop ectopic
      calcifications in a variety of soft tissues - most notably in the skin, cartilage
      elements, the heart, intracranial space and the notochord sheet. Using transgenic
      reporter lines, we demonstrate that ectopic mineralizations in these tissues
      occur independently of the expression of typical osteoblast or cartilage markers.
      Intriguingly, we detect cells expressing the osteoclast markers Trap and
      CathepsinK at sites of ectopic calcification at time points when osteoclasts are
      not yet present in wild-type siblings. Treatment with the bisphosphonate
      etidronate rescues aspects of the dgf phenotype, and we detected deregulated
      expression of genes that are involved in phosphate homeostasis and
      mineralization, such as fgf23, npt2a, entpd5 and spp1 (also known as
      osteopontin). Employing a UAS-GalFF approach, we show that forced expression of
      enpp1 in blood vessels or the floorplate of mutant embryos is sufficient to
      rescue the notochord mineralization phenotype. This indicates that enpp1 can
      exert its function in tissues that are remote from its site of expression. 

PMID- 24906372
TI  - Notch signaling deficiency underlies age-dependent depletion of satellite cells
      in muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a devastating disease characterized by
      muscle wasting, loss of mobility and death in early adulthood. Satellite cells
      are muscle-resident stem cells responsible for the repair and regeneration of
      damaged muscles. One pathological feature of DMD is the progressive depletion of
      satellite cells, leading to the failure of muscle repair. Here, we attempted to
      explore the molecular mechanisms underlying satellite cell ablation in the
      dystrophin mutant mdx mouse, a well-established model for DMD. Initial muscle
      degeneration activates satellite cells, resulting in increased satellite cell
      number in young mdx mice. This is followed by rapid loss of satellite cells with
      age due to the reduced self-renewal ability of mdx satellite cells. In addition,
      satellite cell composition is altered even in young mdx mice, with significant
      reductions in the abundance of non-committed (Pax7+ and Myf5-) satellite cells.
      Using a Notch-reporter mouse, we found that the mdx satellite cells have reduced
      activation of Notch signaling, which has been shown to be necessary to maintain
      satellite cell quiescence and self-renewal. Concomitantly, the expression of
      Notch1, Notch3, Jag1, Hey1 and HeyL are reduced in the mdx primary myoblast.
      Finally, we established a mouse model to constitutively activate Notch signaling
      in satellite cells, and show that Notch activation is sufficient to rescue the
      self-renewal deficiencies of mdx satellite cells. These results demonstrate that
      Notch signaling is essential for maintaining the satellite cell pool and that its
      deficiency leads to depletion of satellite cells in DMD.

PMID- 24906374
TI  - The effect of single session bi-cephalic transcranial direct current stimulation
      on gait performance in sub-acute stroke: A pilot study.
AB  - PURPOSE: Non-invasive brain stimulation with transcranial direct current
      stimulation (tDCS) modulates cortical excitability and improves upper limb motor
      performance when applied to chronic stroke patients. The objective was to
      evaluate whether tDCS can influence gait function in sub-acute stroke patients.
      METHODS: We assessed the effect of single session, bi-cephalic tDCS on gait
      performance in 14 subacute patients with stroke involving the cerebral hemisphere
      (2-8 weeks post-stroke) in a double-blinded, sham-controlled study. Patients were
      randomly allocated to receive either active (n = 7) or sham (n = 7) tDCS. The
      anodal electrode was placed on the scalp over the ipsilesional lower limb primary
      motor cortex and the cathode was placed over the contralesional leg motor cortex.
      Gait performance was measured using the Timed Up and Go test and the Performance
      Oriented Mobility Assessment before and after active or sham tDCS. RESULTS: The
      tDCS group was significantly quicker in the Timed Up and Go test in the tDCS
      group, compared to the sham group (p = 0.018). The Performance Oriented Mobility
      Assessment was not different between groups (p = 0.897). CONCLUSIONS: This is the
      first study to examine the effects of tDCS on gait in stroke patients in the sub
      acute stage. Active tDCS improved gait performance (Timed Up and Go) in stroke
      patients, despite no changes to limb biomechanics of the hemiparetic side
      (Performance Oriented Mobility Assessment), as compared to sham stimulation.
      These results suggest that tDCS could be used as a therapeutic adjunct for gait
      rehabilitation following stroke.

PMID- 24906373
TI  - Cold temperature improves mobility and survival in Drosophila models of autosomal
      dominant hereditary spastic paraplegia (AD-HSP).
AB  - Autosomal-dominant hereditary spastic paraplegia (AD-HSP) is a crippling
      neurodegenerative disease for which effective treatment or cure remains unknown.
      Victims experience progressive mobility loss due to degeneration of the longest
      axons in the spinal cord. Over half of AD-HSP cases arise from loss-of-function
      mutations in spastin, which encodes a microtubule-severing AAA ATPase. In
      Drosophila models of AD-HSP, larvae lacking Spastin exhibit abnormal motor neuron
      morphology and function, and most die as pupae. Adult survivors display impaired
      mobility, reminiscent of the human disease. Here, we show that rearing pupae or
      adults at reduced temperature (18 degrees C), compared with the standard
      temperature of 24 degrees C, improves the survival and mobility of adult spastin
      mutants but leaves wild-type flies unaffected. Flies expressing human spastin
      with pathogenic mutations are similarly rescued. Additionally, larval cooling
      partially rescues the larval synaptic phenotype. Cooling thus alleviates known
      spastin phenotypes for each developmental stage at which it is administered and,
      notably, is effective even in mature adults. We find further that cold treatment
      rescues larval synaptic defects in flies with mutations in Flower (a protein with
      no known relation to Spastin) and mobility defects in flies lacking Kat60-L1,
      another microtubule-severing protein enriched in the CNS. Together, these data
      support the hypothesis that the beneficial effects of cold extend beyond specific
      alleviation of Spastin dysfunction, to at least a subset of cellular and
      behavioral neuronal defects. Mild hypothermia, a common neuroprotective technique
      in clinical treatment of acute anoxia, might thus hold additional promise as a
      therapeutic approach for AD-HSP and, potentially, for other neurodegenerative
      diseases. 

PMID- 24906375
TI  - Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two
      returning travellers in the Netherlands, May 2014.
AB  - Two patients, returning to the Netherlands from pilgrimage in Medina and Mecca,
      Kingdom of Saudi Arabia, were diagnosed with Middle East respiratory syndrome
      coronavirus (MERS-CoV) infection in May 2014. The source and mode of transmission
      have not yet been determined. Hospital-acquired infection and community-acquired
      infection are both possible.

PMID- 24906376
TI  - Suspected new wave of muscular sarcocystosis in travellers returning from Tioman
      Island, Malaysia, May 2014.
AB  - In May 2014, six patients presented in Germany with a Sarcocystis-associated
      febrile myositis syndrome after returning from Tioman Island, Malaysia. During
      two earlier waves of infections, in 2011 and 2012, about 100 travellers returning
      to various European countries from the island were affected. While the first two
      waves were associated with travel to Tioman Island mostly during the summer
      months, this current series of infections is associated with travel in early
      spring, possibly indicating an upcoming new epidemic.

PMID- 24906377
TI  - Transfusion-transmitted hepatitis E in Germany, 2013.
AB  - The reported IgG seroprevalence against hepatitis E virus (HEV) in German blood
      donations is 6.8%, and HEV RNA detected in 0.08%, but documented evidence for HEV
      transmission is lacking. We identified two donations from a single donor
      containing 120 IU HEV RNA/mL plasma and 490 IU/mL. An infectious dose of 7,056 IU
      HEV RNA was transmitted via apheresis platelets to an immunosuppressed patient
      who developed chronic HEV. Further, transmission was probable in an
      immunocompetent child.

PMID- 24906378
TI  - The Italian national surgical site infection surveillance programme and its
      positive impact, 2009 to 2011.
AB  - Programmes surveying surgical site infection (SSI) have been implemented
      throughout the world and are associated with a reduction in SSI rates. We report
      data on non-prosthetic surgery from the Italian SSI surveillance programme for
      the period 2009 to 2011. Participation in the programme was voluntary. We
      evaluated the occurrence of SSI, based on protocols from the European Centre for
      Disease Prevention and Control, within 30 days of surgery. Demographic data, risk
      factors, type of surgery and presence of SSI were recorded. The National
      Coordinating Centre analysed the pooled data. On 355 surgical wards 60,460
      operations were recorded, with the number of surveyed intervention doubling over
      the study period. SSI was observed in 1,628 cases (2,6%) and 60% of SSI were
      diagnosed through 30-days post discharge surveillance. Operations performed in
      hospitals with at least two years of surveillance showed a 29% lower risk of SSI.
      Longer intervention duration, American Society of Anesthesiologists' (ASA) score
      of at least three, and pre-surgery hospital stay of at least two days were
      associated with increased risk of SSI, while videoscopic procedures had reduced
      SSI rates. Implementation of a national surveillance programme was helpful in
      reducing SSI rates and should be prioritised in all healthcare systems.

PMID- 24906379
TI  - ePathGen--a new e-learning package in pathogen genomics.

PMID- 24906381
TI  - Metabolomics of Ramadan fasting: an opportunity for the controlled study of
      physiological responses to food intake.
AB  - High-throughput screening techniques that analyze the metabolic endpoints of
      biological processes can identify the contributions of genetic predisposition and
      environmental factors to the development of common diseases. Studies applying
      controlled physiological challenges can reveal dysregulation in metabolic
      responses that may be predictive for or associated with these diseases. However,
      large-scale epidemiological studies with well controlled physiological challenge
      conditions, such as extended fasting periods and defined food intake, pose
      logistic challenges. Culturally and religiously motivated behavioral patterns of
      life style changes provide a natural setting that can be used to enroll a large
      number of study volunteers. Here we report a proof of principle study conducted
      within a Muslim community, showing that a metabolomics study during the Holy
      Month of Ramadan can provide a unique opportunity to explore the pre-prandial and
      postprandial response of human metabolism to nutritional challenges. Up to five
      blood samples were obtained from eleven healthy male volunteers, taken directly
      before and two hours after consumption of a controlled meal in the evening on
      days 7 and 26 of Ramadan, and after an over-night fast several weeks after
      Ramadan. The observed increases in glucose, insulin and lactate levels at the
      postprandial time point confirm the expected physiological response to food
      intake. Targeted metabolomics further revealed significant and physiologically
      plausible responses to food intake by an increase in bile acid and amino acid
      levels and a decrease in long-chain acyl-carnitine and polyamine levels. A
      decrease in the concentrations of a number of phospholipids between samples taken
      on days 7 and 26 of Ramadan shows that the long-term response to extended fasting
      may differ from the response to short-term fasting. The present study design is
      scalable to larger populations and may be extended to the study of the metabolic
      response in defined patient groups such as individuals with type 2 diabetes. 

PMID- 24906382
TI  - Profiling the orphan enzymes.
AB  - The emergence of Next Generation Sequencing generates an incredible amount of
      sequence and great potential for new enzyme discovery. Despite this huge amount
      of data and the profusion of bioinformatic methods for function prediction, a
      large part of known enzyme activities is still lacking an associated protein
      sequence. These particular activities are called "orphan enzymes". The present
      review proposes an update of previous surveys on orphan enzymes by mining the
      current content of public databases. While the percentage of orphan enzyme
      activities has decreased from 38% to 22% in ten years, there are still more than
      1,000 orphans among the 5,000 entries of the Enzyme Commission (EC)
      classification. Taking into account all the reactions present in metabolic
      databases, this proportion dramatically increases to reach nearly 50% of orphans
      and many of them are not associated to a known pathway. We extended our survey to
      "local orphan enzymes" that are activities which have no representative sequence
      in a given clade, but have at least one in organisms belonging to other clades.
      We observe an important bias in Archaea and find that in general more than 30% of
      the EC activities have incomplete sequence information in at least one
      superkingdom. To estimate if candidate proteins for local orphans could be
      retrieved by homology search, we applied a simple strategy based on the PRIAM
      software and noticed that candidates may be proposed for an important fraction of
      local orphan enzymes. Finally, by studying relation between protein domains and
      catalyzed activities, it appears that newly discovered enzymes are mostly
      associated with already known enzyme domains. Thus, the exploration of the
      promiscuity and the multifunctional aspect of known enzyme families may solve
      part of the orphan enzyme issue. We conclude this review with a presentation of
      recent initiatives in finding proteins for orphan enzymes and in extending the
      enzyme world by the discovery of new activities.

PMID- 24906383
TI  - Getting lipids from glycerol: new perspectives on biotechnological exploitation
      of Candida freyschussii.
AB  - BACKGROUND: Microbial lipids represent a valuable alternative feedstock for
      biodiesel production when oleaginous microbes are cultured with inexpensive
      substrates in processes exhibiting high yield and productivity. In this
      perspective, crude glycerol is among the most promising raw materials for lipid
      production, because it is the costless residual of biodiesel production. Thus,
      cultivation of oleaginous yeasts in glycerol-based media is attracting great
      interest and natural biodiversity is increasingly explored to identify novel
      oleaginous species recycling this carbon source for growth and lipid production.
      RESULTS: Thirty-three yeasts strains belonging to 19 species were screened for
      the ability to grow and produce intracellular lipids in a pure glycerol-based
      medium with high C/N ratio. A minority of them consumed most of the glycerol and
      generated visible lipid bodies. Among them, Candida freyschussii ATCC 18737 was
      selected, because it exhibited the highest lipid production and glycerol
      conversion yield. Lipid production in this strain was positively affected by the
      increase of C/N ratio, but growth was inhibited by glycerol concentration higher
      than 40 g/L. In batch cultures, the highest lipid production (4.6 g/L), lipid
      content of biomass (33% w/w), and lipid volumetric productivity (0.15 g/L/h) were
      obtained with 40 g/L glycerol, during the course of a 30-h process. Fed-batch
      cultivation succeeded in preventing substrate inhibition and in achieving a high
      cell-density culture. The improved lipid production and volumetric productivity
      reached the remarkable high level of 28 g/L and 0.28 g/L/h, respectively. The
      lipids accumulated by C. freyschussii ATCC 18737 have similar fatty acid
      composition of plant oil indicating their potential use as biodiesel feedstock.
      Calculated physicochemical properties of a biodiesel produced with the lipids
      from C. freyschussii ATCC 18737 are expected to meet the European and American
      standards, being equal to those of rapeseed and palm biodiesel. CONCLUSIONS: C.
      freyschussii ATCC 18737 could be considered an interesting microorganism for
      utilization in biofuel industry. Cultivation of this yeast in media containing
      crude glycerol should be investigated deeper in order to evaluate whether it may
      find application in the valorization of the waste of biodiesel manufacturing.

PMID- 24906384
TI  - Recurrent differentiated thyroid cancer: towards personalized treatment based on
      evaluation of tumor characteristics with PET (THYROPET Study): study protocol of
      a multicenter observational cohort study.
AB  - BACKGROUND: After initial treatment of differentiated thyroid carcinoma (DTC)
      patients are followed with thyroglobulin (Tg) measurements to detect recurrences.
      In case of elevated levels of Tg and negative neck ultrasonography, patients are
      treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the
      post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients
      derive no benefit from the blind therapy but are exposed to its toxicity.
      Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography
      (PET/CT) has become available to visualize DTC lesions and without toxicity. In
      addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent
      DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the
      combination of 124I and 18F-FDG PET/CT has potential to stratify patients for
      treatment with 131I. METHODS/DESIGN: In a multicenter prospective observational
      cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can
      avoid futile 131I treatments in patients planned for 'blind' therapy with 131I,
      is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG
      PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all
      patients will subsequently receive, after thyroid hormone withdrawal, the 131I
      therapy. The post 131I therapeutic scintigraphy is compared with the outcome of
      the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the
      combined PET modalities.This study primary aims to reduce the number of futile
      131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by
      a quality assurance and quality control (QA/QC) program, to correlate imaging
      outcome with histopathological features, to compare 124I PET/CT after rhTSH and
      after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.
      DISCUSSION: This study aims to evaluate the potential value of the combination of
      124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients
      with biochemically suspected recurrence of DTC. To our best knowledge no studies
      addressed this in a prospective cohort of patients. This is of great clinical
      importance as a futile 131I is a costly treatment associated with morbidity and
      therefore should be restricted to those likely to benefit from this treatment.
      TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01641679.

PMID- 24906387
TI  - A survey of pathogens associated with Cyperus esculentus L (tiger nuts) tubers
      sold in a Ghanaian city.
AB  - BACKGROUND: Cyperus esculentus L, is a minor but important crop in Ghana. They
      are noted mostly by their aphrodisiac properties among others. The nuts are often
      eaten raw as an unprocessed snack due to its rich flavour and texture. Though
      eaten raw, the nuts are sometimes handled unhygienically, posing a public health
      threat. This study therefore aimed at determining the level and distribution of
      parasitic and bacterial contaminants associated with the crop as it is sold.
      RESULTS: Four types of intestinal parasites were identified, and the most
      prevalent was Cryptosporidium parvum (30.0%). Nuts contaminated with parasites
      were found only among street vendors. Bacteriological examination showed three
      different groups of bacterial isolates with the most prevalent being coliforms
      (54.2%). Unlike parasites, bacteria isolates were found among samples from both
      street vendors and market places. Multiple drug resistance was displayed by
      Proteus vulgaris. CONCLUSIONS: Buying and eating nuts as well as other fruits
      taken raw from street vendors and market places could pose a significant public
      health threat. There is a need for efficient monitoring systems for food borne
      pathogens in Ghana.

PMID- 24906385
TI  - The genetic diversity of cereulide biosynthesis gene cluster indicates a
      composite transposon Tnces in emetic Bacillus weihenstephanensis.
AB  - BACKGROUND: Cereulide is a cyclic dodecadepsipeptide ionophore, produced via non
      ribosomal peptide synthetases (NRPS), which in rare cases can lead to human
      death. Early studies had shown that emetic toxin formation belongs to a
      homogeneous group of Bacillus cereus sensu stricto and the genetic determinants
      of cereulide (a 24-kb gene cluster of cesHPTABCD) are located on a 270-kb plasmid
      related to the Bacillus anthracis virulence plasmid pXO1. RESULTS: The whole
      genome sequences from seven emetic isolates, including two B. cereus sensu
      stricto and five Bacillus weihenstephanensis strains, were compared, and their
      inside and adjacent DNA sequences of the cereulide biosynthesis gene clusters
      were analyzed. The sequence diversity was observed, which classified the seven
      emetic isolates into three clades. Different genomic locations of the cereulide
      biosynthesis gene clusters, plasmid-borne and chromosome-borne, were also found.
      Potential mobile genetic elements (MGEs) were identified in the flanking
      sequences of the ces gene cluster in all three types. The most striking
      observation was the identification of a putative composite transposon, Tnces,
      consisting of two copies of ISces element (belonging to IS6 family) in opposite
      orientations flanking the ces gene cluster in emetic B. weihenstephanensis. The
      mobility of this element was tested by replacing the ces gene cluster by a KmR
      gene marker and performing mating-out transposition assays in Escherichia coli.
      The results showed that Tnces::km transposes efficiently (1.04 * 10(-3) T/R) and
      produces 8-bp direct repeat (DR) at the insertion sites. CONCLUSIONS: Cereulide
      biosynthesis gene clusters display sequence diversity, different genomic
      locations and association with MGEs, in which the transposition capacity of a
      resistant derivative of the composite transposon Tnces in E. coli was
      demonstrated. Further study is needed to look for appropriate genetic tools to
      analysis the transposition of Tnces in Bacillus spp. and the dynamics of other
      MGEs flanking the ces gene clusters.

PMID- 24906388
TI  - Patterns of failure for glioblastoma multiforme following limited-margin
      radiation and concurrent temozolomide.
AB  - BACKGROUND: To analyze patterns of failure in patients with glioblastoma
      multiforme (GBM) treated with limited-margin radiation therapy and concurrent
      temozolomide. We hypothesize that patients treated with margins in accordance
      with Adult Brain Tumor Consortium guidelines (ABTC) will demonstrate patterns of
      failure consistent with previous series of patients treated with 2-3 cm margins.
      METHODS: A retrospective review was performed of patients treated at the
      University of Alabama at Birmingham for GBM between 2000 and 2011. Ninety-five
      patients with biopsy-proven disease and documented disease progression after
      treatment were analyzed. The initial planning target volume includes the T1
      enhancing tumor and surrounding edema plus a 1 cm margin. The boost planning
      target volume includes the T1-enhancing tumor plus a 1 cm margin. The tumors were
      classified as in-field, marginal, or distant if greater than 80%, 20-80%, or less
      than 20% of the recurrent volume fell within the 95% isodose line, respectively.
      RESULTS: The median progression-free survival from the time of diagnosis to
      documented failure was 8 months (range 3-46). Of the 95 documented recurrences,
      77 patients (81%) had an in-field component of treatment failure, 6 (6%) had a
      marginal component, and 27 (28%) had a distant component. Sixty-three patients
      (66%) demonstrated in-field only recurrence. CONCLUSIONS: The low rate of
      marginal recurrence suggests that wider margins would have little impact on the
      pattern of failure, validating the use of limited margins in accordance ABTC
      guidelines.

PMID- 24906389
TI  - Whole-genome sequencing of Mesorhizobium huakuii 7653R provides molecular
      insights into host specificity and symbiosis island dynamics.
AB  - BACKGROUND: Evidence based on genomic sequences is urgently needed to confirm the
      phylogenetic relationship between Mesorhizobium strain MAFF303099 and M. huakuii.
      To define underlying causes for the rather striking difference in host
      specificity between M. huakuii strain 7653R and MAFF303099, several probable
      determinants also require comparison at the genomic level. An improved
      understanding of mobile genetic elements that can be integrated into the main
      chromosomes of Mesorhizobium to form genomic islands would enrich our knowledge
      of how genome dynamics may contribute to Mesorhizobium evolution in general.
      RESULTS: In this study, we sequenced the complete genome of 7653R and compared it
      with five other Mesorhizobium genomes. Genomes of 7653R and MAFF303099 were found
      to share a large set of orthologs and, most importantly, a conserved chromosomal
      backbone and even larger perfectly conserved synteny blocks. We also identified
      candidate molecular differences responsible for the different host specificities
      of these two strains. Finally, we reconstructed an ancestral Mesorhizobium
      genomic island that has evolved into diverse forms in different Mesorhizobium
      species. CONCLUSIONS: Our ortholog and synteny analyses firmly establish
      MAFF303099 as a strain of M. huakuii. Differences in nodulation factors and
      secretion systems T3SS, T4SS, and T6SS may be responsible for the unique host
      specificities of 7653R and MAFF303099 strains. The plasmids of 7653R may have
      arisen by excision of the original genomic island from the 7653R chromosome.

PMID- 24906391
TI  - Priority setting in Indigenous health: assessing priority setting process and
      criteria that should guide the health system to improve Indigenous Australian
      health.
AB  - INTRODUCTION: The health of Indigenous Australians is worse than that of other
      Australians. Most of the determinants of health are preventable and the poor
      health outcomes are inequitable. The Australian Government recently pledged to
      close that health gap. One possible way is to improve the priority setting
      process to ensure transparency and the use of evidence such as epidemiology,
      equity and economic evaluation.The purpose of this research was to elicit the
      perceptions of Indigenous and non-Indigenous decision-makers on several issues
      related to priority setting in Indigenous-specific health care services.
      Specifically, we aimed to:1. identify the criteria used to set priorities in
      Indigenous-specific health care services;2. determine the level of uptake of
      economic evaluation evidence by decision-makers and how to improve its uptake;
      and 3. identify how the priority setting process can be improved from the
      perspective of decision-makers. METHODS: We used a paper survey instrument,
      adapted from Mitton and colleagues' work, and a face-to-face interview approach
      to elicit decision-makers' perceptions in Indigenous-specific health care in
      Victoria, Australia. We used mixed methods to analyse data from the survey.
      Responses were summarised using descriptive statistics and content analysis.
      Results were reported as numbers and percentages. RESULTS: The size of the health
      burden; sustainability and acceptability of interventions; historical
      trends/patterns; and efficiency are key criteria for making choices in Indigenous
      health in Victoria. There is a need for an explicit priority setting approach,
      which is systematic, and is able to use available data/evidence, such as economic
      evaluation evidence. The involvement of Indigenous Australians in the process
      would potentially make the process acceptable. CONCLUSIONS: An economic approach
      to priority setting is a potentially acceptable and useful tool for Aboriginal
      Community Controlled Health Services (ACCHS). It has the ability to use evidence
      and ensure due process at the same time. The use of evidence can ensure that
      health outcomes for Indigenous peoples can be maximised - hence, increase the
      potential for 'closing the gap' between Indigenous and other Australians.

PMID- 24906392
TI  - Qualitative process evaluation of a problem-solving guided self-help manual for
      family carers of young people with first-episode psychosis.
AB  - BACKGROUND: Caring for a young person experiencing first-episode psychosis is
      challenging and can affect carers' well-being adversely. While some face-to-face
      approaches have achieved promising outcomes, they are costly and resource
      intensive to provide, restricting their reach and penetration. Guided self-help
      in book-form (or bibliotherapy) is an alternative but untested approach in these
      circumstances. In this study, we aimed to evaluate carers' beliefs about the
      usefulness of problem-solving guided self-help manual for primary carers of young
      people with first-episode psychosis. METHODS: A qualitative process evaluation
      nested in a randomised controlled trial, conducted across two early intervention
      psychosis services in Melbourne, Australia. 124 carers were randomised to problem
      solving guided self-help intervention or treatment as usual. We also undertook a
      qualitative process evaluation, using individual interviews, with a random sample
      of 24 of the intervention group. A thematic analysis of the qualitative data was
      undertaken, which is the subject of this paper. Interviews were conducted between
      January 2009 and September 2010. RESULTS: Three themes were abstracted from the
      data, reflecting carers' beliefs about the usefulness of the manual: promoting
      carers' well-being, increasing carers' understanding of and support for the young
      person with first-episode psychosis, and accessibility and delivery modes of the
      programme. CONCLUSION: This process evaluation highlights that guided self-help
      is useful in informing and supporting carers of affected young people. While
      there is scope for broadening the delivery modes, the approach is easy to use and
      accessible, and can be used as a cost-effective adjunct to standard support
      provided to carers, by community mental health nurses and other clinicians. TRIAL
      REGISTRATION: ACTRN12609000064202.

PMID- 24906393
TI  - Environment and subjective well-being of rural Chinese elderly: a multilevel
      analysis.
AB  - INTRODUCTION: The purpose of this study was to examine the effects of environment
      on the subjective well-being (SWB) of older Chinese villagers after controlling
      for personal and social characteristics. METHOD: Data collected from the Chinese
      Health and Retirement Longitudinal Survey Pilot Study were used to examine the
      relationship between (a) SWB (i.e., happiness and depressive symptoms) of Chinese
      rural elderly and (b) environmental characteristics, controlling for personal and
      social characteristics. A total of 850 older villagers from 2 Chinese provinces
      were analyzed using multilevel regression models. RESULTS: Five of the 8
      environmental variables had significant effects on SWB: A natural disaster in the
      past 5 years, rainy days, and use of coal in the home were associated with lower
      SWB, whereas village wealth and sewer system were associated with higher SWB.
      Personal and social characteristics of importance included health, age, place of
      birth, perception that future help is available if needed, and providing help to
      others. DISCUSSION: The proposition that the environment of older Chinese
      villagers is associated with their SWB was supported after accounting for
      personal and social characteristics. SWB may be improved by improving
      environments as well as by changes to personal and social conditions.

PMID- 24906390
TI  - The ever-expanding conundrum of primary osteoporosis: aetiopathogenesis,
      diagnosis, and treatment.
AB  - In recent years, as knowledge regarding the etiopathogenetic mechanisms of bone
      involvement characterizing many diseases has increased and diagnostic techniques
      evaluating bone health have progressively improved, the problem of low bone
      mass/quality in children and adolescents has attracted more and more attention,
      and the body evidence that there are groups of children who may be at risk of
      osteoporosis has grown. This interest is linked to an increased understanding
      that a higher peak bone mass (PBM) may be one of the most important determinants
      affecting the age of onset of osteoporosis in adulthood. This review provides an
      updated picture of bone pathophysiology and characteristics in children and
      adolescents with paediatric osteoporosis, taking into account the major causes of
      primary osteoporosis (PO) and evaluating the major aspects of bone densitometry
      in these patients. Finally, some options for the treatment of PO will be briefly
      discussed. 

PMID- 24906394
TI  - Fine particulate matter air pollution and cognitive function among U.S. older
      adults.
AB  - OBJECTIVES: There is growing interest in understanding how exposures in the
      residential environment relate to cognitive function in older adults. The goal of
      this study is to determine if neighborhood-level exposure to fine particulate
      matter air pollution (PM2.5) is associated with cognitive function in a diverse,
      national sample of older U.S. adults. METHODS: We use cross-sectional data on non
      Hispanic black and white men and women aged 55 and older from the 2001/2002
      Americans' Changing Lives Study (N = 780). EPA air monitoring data were linked to
      respondents using census tract identifiers. Cognitive function was assessed with
      tests of working memory and orientation. Negative binomial regression models were
      used to examine the association between PM2.5 and the number of errors on the
      cognitive assessment. RESULTS: Older adults living in areas with high
      concentrations of PM2.5 had an error rate 1.5 times greater than those exposed to
      lower concentrations, net of individual and neighborhood-level demographic and
      socioeconomic characteristics. DISCUSSION: This study adds to a growing body of
      research demonstrating the importance of air pollution to cognitive function in
      older adults. Improvements to air quality may be an important mechanism for
      reducing age-related cognitive decline.

PMID- 24906395
TI  - Exposure to stressors and trajectories of perceived stress among older adults.
AB  - OBJECTIVES: Models of stress incorporate both the environmental demands
      experienced by individuals (stressors) and the appraisal of these life events
      (perceptions). Because little is known about the extent to which experience and
      perceptions are related, we examine this relationship in a nationally
      representative population of older Taiwanese adults. METHOD: Using growth models
      applied to data from 3 waves (1999, 2003, and 2007) of the Taiwan Longitudinal
      Study of Aging, we (a) investigate patterns of change in perceived stress in
      later adulthood and (b) examine how experienced stressors influence perceived
      stress. Participants were asked to report the presence of, and in some cases the
      degree of, exposure to stressors including total number of medical conditions,
      difficulty with activities of daily living, difficulty with mobility functions,
      being financially worse off compared with the prior wave, experiencing the death
      of a child, and experiencing a marital disruption. Items reflecting perceived
      stress included concerns about various domains pertaining to the respondent and
      his/her family member. RESULTS: Our results indicate that exposure to stressors
      increases, whereas perceived stress decreases, over time. Change in exposure to
      stressors is not generally associated with change in perceptions of stress, with
      the exception of a summary measure of health-related exposure to stressors. An
      increase in poor health over time is related to an increase in perceived stress
      in all domains. DISCUSSION: The results underscore the importance of
      distinguishing between perceptions of stress and exposure to stressors when
      studying the links between stress and health among older adults. Furthermore, the
      diminishing linkage between experienced stressors and perceptions of stress
      suggests that older adults' appraisal may be an adaptive coping strategy that
      emerges to buffer some of the difficulties that are inevitable in later life.

PMID- 24906396
TI  - Incorporating immigrants: integrating theoretical frameworks of adaptation.
AB  - OBJECTIVES: To encourage research on immigrants and aging by analyzing
      theoretical commonalities in the two fields and identifying potential
      contributions of aging theories, specifically to the understanding of neglected
      age differences in the pace of immigrant incorporation. METHODS: Survey of the
      historical development of assimilation theory and its successors and systematic
      comparison of key concepts in aging and immigrant incorporation theories.
      RESULTS: Studies of immigrants, as well as of the life course, trace their
      origins to the Chicago School at the turn of the 20th century. Today, both
      theoretical perspectives emphasize adaptation as a time-dependent,
      multidimensional, nonlinear, and multidirectional process. Immigrant
      incorporation theories have not fully engaged with a key concern of aging theory
      why there are age differences. Insights from cognitive aging and developmental
      biology, life-span developmental psychology, and age stratification and the life
      course suggest explanations for age differences in the speed of immigrant
      incorporation. DISCUSSION: Theories of adaptation to aging and theories of
      immigrant incorporation developed so independently that they neglected the
      subject they have in common, namely, older immigrants. Because they address
      similar conceptual problems and share key assumptions, a productive dialogue
      between two vibrant fields is long overdue.

PMID- 24906398
TI  - Re: Denosumab for patients with persistent or relapsed hypercalcemia of
      malignancy despite recent bisphosphonate treatment.

PMID- 24906397
TI  - Effects of a novel long noncoding RNA, lncUSMycN, on N-Myc expression and
      neuroblastoma progression.
AB  - BACKGROUND: Patients with neuroblastoma due to the amplification of a 130-kb
      genomic DNA region containing the MYCN oncogene have poor prognoses. METHODS:
      Bioinformatics data were used to discover a novel long noncoding RNA, lncUSMycN,
      at the 130-kb amplicon. RNA-protein pull-down assays were used to identify
      proteins bound to lncUSMycN RNA. Kaplan-Meier survival analysis, multivariable
      Cox regression, and two-sided log-rank test were used to examine the prognostic
      value of lncUSMycN and NonO expression in three cohorts of neuroblastoma patients
      (n = 47, 88, and 476, respectively). Neuroblastoma-bearing mice were treated with
      antisense oligonucleotides targeting lncUSMycN (n = 12) or mismatch sequence (n =
      13), and results were analyzed by multiple comparison two-way analysis of
      variance. All statistical tests were two-sided. RESULTS: Bioinformatics data
      predicted lncUSMycN gene and RNA, and reverse-transcription polymerase chain
      reaction confirmed its three exons and two introns. The lncUSMycN gene was
      coamplified with MYCN in 88 of 341 human neuroblastoma tissues. lncUSMycN RNA
      bound to the RNA-binding protein NonO, leading to N-Myc RNA upregulation and
      neuroblastoma cell proliferation. High levels of lncUSMycN and NonO expression in
      human neuroblastoma tissues independently predicted poor patient prognoses
      (lncUSMycN: hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.06 to
      3.28, P = .03; NonO: HR = 2.48, 95% CI = 1.34 to 4.57, P = .004). Treatment with
      antisense oligonucleotides targeting lncUSMycN in neuroblastoma-bearing mice
      statistically significantly hindered tumor progression (P < .001). CONCLUSIONS:
      Our data demonstrate the important roles of lncUSMycN and NonO in regulating N
      Myc expression and neuroblastoma oncogenesis and provide the first evidence that
      amplification of long noncoding RNA genes can contribute to tumorigenesis.

PMID- 24906399
TI  - Response.

PMID- 24906401
TI  - Alexander Nikolaevich Scriabin (1872-1915): Enlightenment or illness?
AB  - The similarity between psychotic symptoms and aspects of mystical experiences is
      well known. It has long been recognized that there are similarities between
      mystical and spiritual and psychotic experiences. The content of an experience
      alone usually does not determine whether an individual is psychotic. The Russian
      composer Scriabin (1872-1915) was among the most famous artists of his time.
      Scriabin infused his music with mysticism, evolving a modernistic idiom through
      which he created a musical counterpart to the Symbolist literature of that
      period. In this paper, we discuss the question that arises from perusing
      Scriabin's life is whether the composer was a mystic genius or whether he
      suffered from affective psychopathology with psychotic features. 

PMID- 24906400
TI  - Long noncoding RNA in neuroblastoma: new light on the (old) N-Myc story.

PMID- 24906402
TI  - The evolution of the discipline of pharmacology amid an era of global turbulence:
      the unique contributions of Otto Krayer (1899-1982).
AB  - This article revisits the life and times of Otto Krayer, a gifted scientist,
      teacher and administrator. His unique contributions to the discipline of
      pharmacology and to the biomedical sciences are chronicled in the wake of the
      political upheaval that crippled German science during the 1930s. The anti
      scientific attitude that pervaded Germany at the time led to the exile of Krayer
      and many other eminent scientists. Their fate is recounted, as well as the
      negative impact on science caused by a National Socialist regime that blatantly
      disregarded basic scientific principles. The threat of intolerance and unethical
      behaviour still remains a key obstacle to scientific creativity. 

PMID- 24906403
TI  - Social contract of academic medical centres to the community: Dr Howard Atwood
      Kelly (1858-1943), a historical perspective.
AB  - Academic medical centres have traditionally been bastions of teaching and
      research. Outreach to the community at large and involvement in community affairs
      have sometimes been lacking in the overall mission and activities of academic
      medical centres. This paper provides an historical perspective first on the
      numerous achievements of a physician and surgeon and then on the topic of
      involvement in community affairs by reviewing the many contributions of America's
      pioneer gynaecological surgeon and one of the four physician founders of the
      Johns Hopkins Hospital and School of Medicine in 1889 - Dr Howard Atwood Kelly. 

PMID- 24906404
TI  - Dr John Dickinson (1832-1863): The man behind the bird.
AB  - The surgeon/naturalists Dr John Kirk, Dr Charles Meller and Dr John Dickinson,
      associated with the Zambezi Expedition (1857-1864) under the leadership of Dr
      David Livingstone are, like him, credited with the discovery of new species' of
      birds. A raptor, Falco dickinsoni, is named after Dr John Dickinson. Dickinson,
      born in the north east of England, trained in medicine in Newcastle upon Tyne. He
      volunteered to join the Universities' Mission to Central Africa and arrived as
      part of a second group to join Bishop Frederick Mackenzie, then attempting to
      build a Mission in Magomero, on the Shire Mountain Plateau in modern Malawi.
      Livingstone and Mackenzie had sown the seeds of disaster for the first UMCA
      venture while Dickinson was on his way to Central Africa, and his one meeting
      with Livingstone was trigger to a chain of events that threatened the whole
      expedition. Shortly after Dickinson's arrival in Magomero, Bishop Mackenzie and a
      fellow traveller, Reverend Henry de Wint Burrup, died. Magomero was abandoned and
      the remaining missionaries retrenched in Chibisa's Village on the River Shire.
      There, where Dickinson did most of his bird collecting, on 17 March 1863, he died
      of blackwater fever. Livingstone and Kirk were present at the burial. A marble
      cross at Chikwawa in Malawi is marker to the event that occurred on the day of Dr
      John Dickinson's 32nd birthday. 

PMID- 24906405
TI  - Comparison of clinical outcome of low-dose and high-dose rabbit antithymocyte
      globulin induction therapy in renal transplantation: a single-center experience.
AB  - BACKGROUND: To explore a better balance between efficacy and complications, we
      respectively compared the clinical outcome of low-dose and high-dose rATG
      induction therapy with a control group in renal transplantations from March 2009
      to March 2012. MATERIAL AND METHODS: 281 kidney transplant recipients were
      included in 3 groups. The low-dose group (n=39) received rATG 1 mg/kg on the
      first day and 0.5 mg/kg on the next consecutive 3 days post-transplantation. The
      high-dose group (n=30) received rATG 1 mg/kg for 6 days. The control group
      (n=212) received no induction therapy. All patients were treated with
      Prednisolone, Mycophenolate mofetil, cyclosporine A, or tacrolimus capsules.
      Acute rejection rates, renal function, CMV infection, patient survival, and the
      adverse effects of rATG were reviewed. RESULTS: The acute rejection rate was
      significantly lower in the rATG group compared with the control group (low-dose
      17.9% vs. control 35.4%, P=0.03, and high-dose 16.7% vs. control 35.4%, P=0.038).
      There was no statistically significant difference in 3-year survival and graft
      survival rates among the groups. Renal function early recovery was similar in the
      rATG and the control group. The CMV infection rate in the high-dose rATG group
      was higher than the low-dose rATG and the control group (p=0.037 and p=0.002,
      respectively). rATG induction therapy was associated with thrombocytopenia in our
      series, especially in the high-dose rATG group. CONCLUSIONS: Low-dose rATG
      induction may be superior to high-dose rATG induction therapy in renal
      transplantation.

PMID- 24906406
TI  - The STRIDE (Strategies to Increase confidence, InDependence and Energy) study:
      cognitive behavioural therapy-based intervention to reduce fear of falling in
      older fallers living in the community - study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Around 30% to 62% of older individuals fall each year, with adverse
      consequences of falls being by no means limited to physical injury and escalating
      levels of dependence. Many older individuals suffer from a variety of adverse
      psychosocial difficulties related to falling including fear, anxiety, loss of
      confidence and subsequent increasing activity avoidance, social isolation and
      frailty. Such 'fear of falling' is common and disabling, but definitive studies
      examining the effective management of the syndrome are lacking. Cognitive
      behavioural therapy has been trialed with some success in a group setting, but
      there is no adequately powered randomised controlled study of an individually
      based cognitive behavioural therapy intervention, and none using non-mental
      health professionals to deliver the intervention. METHODS/DESIGN: We are
      conducting a two-phase study examining the role of individual cognitive
      behavioural therapy delivered by healthcare assistants in improving fear of
      falling in older adults. In Phase I, the intervention was developed and taught to
      healthcare assistants, while Phase II is the pragmatic randomised controlled
      study examining the efficacy of the intervention in improving fear of falling in
      community-dwelling elders attending falls services. A qualitative process
      evaluation study informed by Normalization Process Theory is being conducted
      throughout to examine the potential promoters and inhibitors of introducing such
      an intervention into routine clinical practice, while a health economic sub-study
      running alongside the trial is examining the costs and benefits of such an
      approach to the wider health economy. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN78396615.

PMID- 24906407
TI  - COUP-TFI modifies CXCL12 and CXCR4 expression by activating EGF signaling and
      stimulates breast cancer cell migration.
AB  - BACKGROUND: The orphan receptors COUP-TF (chicken ovalbumin upstream promoter
      transcription factor) I and II are members of the nuclear receptor superfamily
      that play distinct and critical roles in vertebrate organogenesis. The
      involvement of COUP-TFs in cancer development has recently been suggested by
      several studies but remains poorly understood. METHODS: MCF-7 breast cancer cells
      overexpressing COUP-TFI and human breast tumors were used to investigate the role
      of COUP-TFI in the regulation of CXCL12/CXCR4 signaling axis in relation to cell
      growth and migration. We used Immunofluorescence, western-blot, RT-PCR,
      Formaldehyde-assisted Isolation of Regulatory Elements (FAIRE) assays, as well as
      cell proliferation and migration assays. RESULTS: Previously, we showed that COUP
      TFI expression is enhanced in breast cancer compared to normal tissue. Here, we
      report that the CXCL12/CXCR4 signaling pathway, a crucial pathway in cell growth
      and migration, is an endogenous target of COUP-TFI in breast cancer cells. The
      overexpression of COUP-TFI in MCF-7 cells inhibits the expression of the
      chemokine CXCL12 and markedly enhances the expression of its receptor, CXCR4. Our
      results demonstrate that the modification of CXCL12/CXCR4 expression by COUP-TFI
      is mediated by the activation of epithelial growth factor (EGF) and the EGF
      receptor. Furthermore, we provide evidence that these effects of COUP-TFI
      increase the growth and motility of MCF-7 cells in response to CXCL12. Cell
      migration toward a CXCL12 gradient was inhibited by AMD3100, a specific
      antagonist of CXCR4, or in the presence of excess CXCL12 in the cell culture
      medium. The expression profiles of CXCR4, CXCR7, CXCL12, and COUP-TFI mRNA in 82
      breast tumors and control non-tumor samples were measured using real-time PCR.
      CXCR4 expression was found to be significantly increased in the tumors and
      correlated with the tumor grade, whereas the expression of CXCL12 was
      significantly decreased in the tumors compared with the healthy samples.
      Significantly higher COUP-TFI mRNA expression was also detected in grade 1
      tumors. CONCLUSIONS: Together, our mechanistic in vitro assays and in vivo
      results suggest that a reduction in chemokine CXCL12 expression, with an
      enhancement of CXCR4 expression, provoked by COUP-TFI, could be associated with
      an increase in the invasive potential of breast cancer cells.

PMID- 24906408
TI  - Effects of chronic social defeat stress on peripheral leptin and its hypothalamic
      actions.
AB  - BACKGROUND: Suppression of body weight and symptom of anorexia are major symptoms
      of depression. Recently, we reported that chronic social defeat stress (CSDS)
      induced suppression of body weight gain and anorexic feeding behavior in rats.
      These abnormalities were the result of disrupted malonyl-coenzyme A (CoA)
      signaling pathway in the hypothalamus. However, the condition of peripheral
      leptin and its hypothalamic downstream signal molecules which regulate
      hypothalamic malonyl-CoA level in the CSDS-exposed rats (CSDS rats) is still
      unknown. RESULTS: CSDS rats showed suppressed body weight gain and food intake.
      The weight of the CSDS rats' epididymal white adipose tissues was decreased when
      compared to the control rats. The plasma cholesterol concentration was decreased
      significantly in the CSDS rats compared to the control rats (P < 0.05). The
      plasma glucose concentration was slightly decreased in the CSDS rats compared to
      the control rats (P < 0.1). The expression of leptin mRNA in epididymal white
      adipose tissues and the plasma leptin concentration were decreased in CSDS rats.
      Furthermore, the phosphorylation of the hypothalamic downstream signals of
      leptin, including extracellular signal-regulated kinase 1/2 (ERK1/2) and signal
      transducer and activator of transcription 3 (STAT3), was decreased in CSDS rats.
      CONCLUSIONS: Our results indicated that decreased peripheral leptin expression in
      CSDS rats could down-regulate the hypothalamic downstream signaling pathways of
      leptin while suppressed food intake. These data indicate that CSDS induces the
      down-regulation of hypothalamic AMPK following the elevation of hypothalamic
      malonyl-CoA levels and is independent of peripheral leptin and glucose.

PMID- 24906409
TI  - Medication safety and chronic kidney disease in older adults prescribed
      metformin: a cross-sectional analysis.
AB  - BACKGROUND: Medication safety in patients with chronic kidney disease (CKD) is a
      growing concern. This is particularly relevant in older adults due to underlying
      CKD. Metformin use is contraindicated in patients with abnormal kidney function;
      however, many patients are potentially prescribed metformin inappropriately. We
      evaluated the prevalence of CKD among older adults prescribed metformin for type
      2 diabetes mellitus using available equations to estimate kidney function and
      examined demographic characteristics of patients who were potentially
      inappropriately prescribed metformin. METHODS: We conducted a cross-sectional
      analysis of older adults aged >= 65 years prescribed metformin from March 2008
      March 2009 at an urban tertiary-care facility in Seattle, Washington, USA. CKD
      was defined using National Kidney Foundation-Kidney Disease Outcomes Quality
      Initiative criteria. Creatinine clearance was calculated using the Cockcroft
      Gault equation; estimated glomerular filtration rate was calculated using the
      abbreviated Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology
      (EPI) Collaboration equations. Regression analyses were used to determine the
      associations between demographic characteristics and prevalent CKD. RESULTS:
      Among 356 subjects (median age 69 years, 52.5% female, 39.4% non-Hispanic black),
      prevalence of stage 3 or greater CKD calculated by any of the equations was
      31.4%. The Cockcroft-Gault equation identified more subjects as having CKD
      (23.7%) than the abbreviated MDRD (21.1%) or CKD-EPI (21.7%) equations (P<0.001).
      Older age (OR=1.13, 95% CI 1.08-1.19) and female sex (OR=2.51, 95% CI 1.44-4.38)
      were associated with increased odds of potentially inappropriate metformin
      prescription due to CKD; non-Hispanic black race was associated with decreased
      odds of potentially inappropriate metformin prescription due to CKD (OR=0.41, 95%
      CI 0.23-0.71). CONCLUSIONS: CKD is common in older adults prescribed metformin
      for type 2 diabetes, raising concern for potentially inappropriate medication
      use. No single equation to estimate kidney function may accurately identify CKD
      in this population. Medication safety deserves greater consideration among
      elderly patients due to the widespread prevalence of CKD.

PMID- 24906410
TI  - Analysis of BRCA1and BRCA2 large genomic rearrangements in Sri Lankan familial
      breast cancer patients and at risk individuals.
AB  - BACKGROUND: Majority of mutations found to date in the BRCA1/BRCA2 genes in
      breast and/or ovarian cancer families are point mutations or small insertions and
      deletions scattered over the coding sequence and splice junctions. Such mutations
      and sequence variants of BRCA1 and BRCA2 genes were previously identified in a
      group of Sri Lankan breast cancer patients. Large genomic rearrangements have
      been characterized in BRCA1 and BRCA2 genes in several populations but these have
      not been characterized in Sri Lankan breast cancer patients. FINDINGS: A cohort
      of familial breast cancer patients (N = 57), at risk individuals (N = 25) and
      healthy controls (N = 23) were analyzed using multiplex ligation-dependent probe
      amplification method to detect BRCA1 and BRCA2 large genomic rearrangements. One
      familial breast cancer patient showed an ambiguous deletion in exon 6 of BRCA1
      gene. Full sequencing of the ambiguous region was used to confirm MLPA results.
      Ambiguous deletion detected by MLPA was found to be a false positive result
      confirming that BRCA1 large genomic rearrangements were absent in the subjects
      studied. No BRCA2 rearrangement was also identified in the cohort. CONCLUSION:
      Thus this study demonstrates that BRCA1 and BRCA2 large genomic rearrangements
      are unlikely to make a significant contribution to aetiology of breast cancer in
      Sri Lanka.

PMID- 24906411
TI  - VibA, a homologue of a transcription factor for fungal heterokaryon
      incompatibility, is involved in antifungal compound production in the plant
      symbiotic fungus Epichloe festucae.
AB  - Symbiotic association of epichloae endophytes (Epichloe/Neotyphodium species)
      with cool-season grasses of the subfamily Pooideae confers bioprotective benefits
      to the host plants against abiotic and biotic stresses. While the production of
      fungal bioprotective metabolites is a well-studied mechanism of host protection
      from insect herbivory, little is known about the antibiosis mechanism against
      grass pathogens by the mutualistic endophyte. In this study, an Epichloe festucae
      mutant defective in antimicrobial substance production was isolated by a
      mutagenesis approach. In an isolated mutant that had lost antifungal activity,
      the exogenous DNA fragment was integrated into the promoter region of the vibA
      gene, encoding a homologue of the transcription factor VIB-1. VIB-1 in Neurospora
      crassa is a regulator of genes essential in vegetative incompatibility and
      promotion of cell death. Here we show that deletion of the vibA gene severely
      affected the antifungal activity of the mutant against the test pathogen
      Drechslera erythrospila. Further analyses showed that overexpressing vibA
      enhanced the antifungal activity of the wild-type isolate against test pathogens.
      Transformants overexpressing vibA showed an inhibitory activity on test pathogens
      that the wild-type isolate could not. Moreover, overexpressing vibA in a
      nonantifungal E. festucae wild-type Fl1 isolate enabled the transformant to
      inhibit the mycelial and spore germination of D. erythrospila. These results
      demonstrate that enhanced expression of vibA is sufficient for a nonantifungal
      isolate to obtain antifungal activity, implicating the critical role of VibA in
      antifungal compound production by epichloae endophytes. 

PMID- 24906412
TI  - Interaction of Cryptococcus neoformans extracellular vesicles with the cell wall.
AB  - Cryptococcus neoformans produces extracellular vesicles containing a variety of
      cargo, including virulence factors. To become extracellular, these vesicles not
      only must be released from the plasma membrane but also must pass through the
      dense matrix of the cell wall. The greatest unknown in the area of fungal
      vesicles is the mechanism by which these vesicles are released to the
      extracellular space given the presence of the fungal cell wall. Here we used
      electron microscopy techniques to image the interactions of vesicles with the
      cell wall. Our goal was to define the ultrastructural morphology of the process
      to gain insights into the mechanisms involved. We describe single and multiple
      vesicle-leaving events, which we hypothesized were due to plasma membrane and
      multivesicular body vesicle origins, respectively. We further utilized melanized
      cells to "trap" vesicles and visualize those passing through the cell wall.
      Vesicle size differed depending on whether vesicles left the cytoplasm in single
      versus multiple release events. Furthermore, we analyzed different vesicle
      populations for vesicle dimensions and protein composition. Proteomic analysis
      tripled the number of proteins known to be associated with vesicles. Despite
      separation of vesicles into batches differing in size, we did not identify major
      differences in protein composition. In summary, our results indicate that
      vesicles are generated by more than one mechanism, that vesicles exit the cell by
      traversing the cell wall, and that vesicle populations exist as a continuum with
      regard to size and protein composition. 

PMID- 24906413
TI  - PFP1, a gene encoding an Epc-N domain-containing protein, is essential for
      pathogenicity of the barley pathogen Rhynchosporium commune.
AB  - Scald caused by Rhynchosporium commune is an important foliar disease of barley.
      Insertion mutagenesis of R. commune generated a nonpathogenic fungal mutant which
      carries the inserted plasmid in the upstream region of a gene named PFP1. The
      characteristic feature of the gene product is an Epc-N domain. This motif is also
      found in homologous proteins shown to be components of histone acetyltransferase
      (HAT) complexes of fungi and animals. Therefore, PFP1 is suggested to be the
      subunit of a HAT complex in R. commune with an essential role in the epigenetic
      control of fungal pathogenicity. Targeted PFP1 disruption also yielded
      nonpathogenic mutants which showed wild-type-like growth ex planta, except for
      the occurrence of hyphal swellings. Complementation of the deletion mutants with
      the wild-type gene reestablished pathogenicity and suppressed the hyphal
      swellings. However, despite wild-type-level PFP1 expression, the complementation
      mutants did not reach wild-type-level virulence. This indicates that the function
      of the protein complex and, thus, fungal virulence are influenced by a position
      affected long-range control of PFP1 expression. 

PMID- 24906414
TI  - The volatome of Aspergillus fumigatus.
AB  - Early detection of invasive aspergillosis is absolutely required for efficient
      therapy of this fungal infection. The identification of fungal volatiles in
      patient breath can be an alternative for the detection of Aspergillus fumigatus
      that still remains problematic. In this work, we investigated the production of
      volatile organic compounds (VOCs) by A. fumigatus in vitro, and we show that
      volatile production depends on the nutritional environment. A. fumigatus produces
      a multiplicity of VOCs, predominantly terpenes and related compounds. The
      production of sesquiterpenoid compounds was found to be strongly induced by
      increased iron concentrations and certain drugs, i.e., pravastatin. Terpenes that
      were always detectable in large amounts were alpha-pinene, camphene, and
      limonene, as well as sesquiterpenes, identified as alpha-bergamotene and beta
      trans-bergamotene. Other substance classes that were found to be present in the
      volatome, such as 1-octen-3-ol, 3-octanone, and pyrazines, were found only under
      specific growth conditions. Drugs that interfere with the terpene biosynthesis
      pathway influenced the composition of the fungal volatome, and most notably, a
      block of sesquiterpene biosynthesis by the bisphosphonate alendronate
      fundamentally changed the VOC composition. Using deletion mutants, we also show
      that a terpene cyclase and a putative kaurene synthase are essential for the
      synthesis of volatile terpenes by A. fumigatus. The present analysis of in vitro
      volatile production by A. fumigatus suggests that VOCs may be used in the
      diagnosis of infections caused by this fungus. 

PMID- 24906415
TI  - Normal telomere length maintenance in Saccharomyces cerevisiae requires nuclear
      import of the ever shorter telomeres 1 (Est1) protein via the importin alpha
      pathway.
AB  - The Est1 (ever shorter telomeres 1) protein is an essential component of yeast
      telomerase, a ribonucleoprotein complex that restores the repetitive sequences at
      chromosome ends (telomeres) that would otherwise be lost during DNA replication.
      Previous work has shown that the telomerase RNA component (TLC1) transits through
      the cytoplasm during telomerase biogenesis, but mechanisms of protein import have
      not been addressed. Here we identify three nuclear localization sequences (NLSs)
      in Est1p. Mutation of the most N-terminal NLS in the context of full-length Est1p
      reduces Est1p nuclear localization and causes telomere shortening-phenotypes that
      are rescued by fusion with the NLS from the simian virus 40 (SV40) large-T
      antigen. In contrast to that of the TLC1 RNA, Est1p nuclear import is facilitated
      by Srp1p, the yeast homolog of importin alpha. The reduction in telomere length
      observed at the semipermissive temperature in a srp1 mutant strain is rescued by
      increased Est1p expression, consistent with a defect in Est1p nuclear import.
      These studies suggest that at least two nuclear import pathways are required to
      achieve normal telomere length homeostasis in yeast. 

PMID- 24906416
TI  - Analysis of peptide PSY1 responding transcripts in the two Arabidopsis plant
      lines: wild type and psy1r receptor mutant.
AB  - BACKGROUND: Small-secreted peptides are emerging as important components in cell
      cell communication during basic developmental stages of plant cell growth and
      development. Plant peptide containing sulfated tyrosine 1 (PSY1) has been
      reported to promote cell expansion and differentiation in the elongation zone of
      roots. PSY1 action is dependent on a receptor PSY1R that triggers a signaling
      cascade leading to cell elongation. However little is known about cellular
      functions and the components involved in PSY1-based signaling cascade. RESULTS:
      Differentially expressed genes were identified in a wild type plant line and in a
      psy1r receptor mutant line of Arabidopsis thaliana after treatment with PSY1.
      Seventy-seven genes were found to be responsive to the PSY1 peptide in wild type
      plants while 154 genes were responsive in the receptor mutant plants. PSY1
      activates the transcripts of genes involved in cell wall modification. Gene
      enrichment analysis revealed that PSY1-responsive genes are involved in responses
      to stimuli, metabolic processes and biosynthetic processes. The significant
      enrichment terms of PSY1-responsive genes were higher in psy1r mutant plants
      compared to in wild type plants. Two parallel responses to PSY1 were identified,
      differing in their dependency on the PSY1R receptor. Promoter analysis of the
      differentially expressed genes identified a light regulatory motif in some of
      these. CONCLUSION: PSY1-responsive genes are involved in cellular functions and
      stimuli responses suggesting a crosstalk between developmental cues and
      environmental stimuli. Possibly, two parallel responses to PSY1 exist. A motif
      involved in light regulation was identified in the promoter region of the
      differentially expressed genes. Reduced hypocotyl growth was observed in
      etiolated receptor mutant seedlings.

PMID- 24906417
TI  - Evaluating geostatistical modeling of exceedance probability as the first step in
      disease cluster investigations: very low birth weights near toxic Texas sites.
AB  - BACKGROUND: The first step in evaluating potential geographic clusters of disease
      calls for an evaluation of the disease risk comparing the risk in a defined
      location to the risk in neighboring locations. Environmental exposures, however,
      represent continuous exposure levels across space not an exposure with a distinct
      boundary. The objectives of the current study were to adapt, apply and evaluate a
      geostatistical approach for identifying disease clusters. METHODS: The exceedance
      probability for very low birth weight (VLBW; < 1.5 kg) infants was mapped using
      an Intrinsic Conditional Autoregressive model. The data were applied to a 20 by
      20 grid of 1 km2 pixels centered on each of the 13 National Priority List
      Superfund Sites in Harris County, Texas. RESULTS: Large clusters of VLBW were
      identified in close proximity to four of the 13 Superfund Sites. Three of the
      Superfund Sites, associated with disease clusters, were located close together in
      central Houston and these sites may have been surrounded by a single, confluent
      disease cluster. CONCLUSIONS: Geostatistical modeling of the exceedance
      probability for very low birth weights identified disease clusters of varying
      size, shape and statistical certainty near Superfund Sites in Harris County,
      Texas. The approach offers considerable potential as the first step for
      investigating potential disease clusters.

PMID- 24906418
TI  - Exploring obesogenic environments: the design and development of the migrant
      obesogenic perception of the environment questionnaire (MOPE-Q) using a sample of
      Iranian migrants in Australia.
AB  - BACKGROUND: Although there are a number of studies examining the effect of
      migration on obesity, these studies tend to focus on the role of acculturation in
      this relationship. However, there are indications that the change in environment
      may also be an important factor. Indeed, there is a considerable lack of
      psychometric tools designed to assess the association between environment and
      migrant health behaviour. The current study aimed to assess the literature on the
      link between environment and health for migrants, and on the basis of this
      information, design and develop the Migrant Obesogenic Perception of the
      Environment questionnaire (MOPE-Q). The MOPE-Q is the first comprehensive measure
      of the impact of environmental factors on migrant health behaviour related to
      physical activity, food habits and body image concern, as well as weight change.
      METHODS: Using a systematic approach, an initial pool of items for the
      questionnaire was developed and refined on the basis of rigorous content and face
      validity assessments and factor analysis. Further, reliability tests and test re
      test studies were undertaken. Differences between Iranian and Australian
      environmental factors as they relate to obesogenic behaviour were explored using
      the developed measure. RESULTS: A total of 36 items were developed for the MOPE
      Q. Principal factor analysis identified three similar factor structures of
      environmental factors related to obesity (categorized in terms of facilitators,
      barriers and pressures) for each country. The final questionnaire consisted of
      four distinct subscales pertaining specifically to the Australian environment and
      five subscales pertaining to the Iranian environment, accounting for 59% and 63%,
      respectively, of the total variance in obesity rates. Data suggests that the MOPE
      Q is a reliable and valid self-report measure for assessing the relationship
      between environmental factors linked to obesity and obesogenic behaviour for this
      particular migrant group. CONCLUSION: The variations in environmental factors
      linked to obesity behaviour between home (Iran) and host (Australia) countries
      have been incorporated into the MOPE-Q instrument which has shown good
      psychometric properties. The MOPE-Q can be adapted and applied to other
      environments and populations to help explain changes in diet, physical activity
      patterns and body weight in migrant groups as they acculturate.

PMID- 24906420
TI  - Yellow-tailed woolly monkey (Lagothrix flavicauda) proximal spacing and forest
      strata use in La Esperanza, Peru.
AB  - Inter-individual spacing of primates and their use of forest strata depend on
      temporal and spatial changes in the environment and on predator avoidance, group
      demography, and social conditions. Greater proximity also increases the chances
      of agonistic and affinitive contact between individuals. I collected behavioral
      data for three groups of yellow-tailed woolly monkeys (Lagothrix flavicauda) by
      instantaneous sampling of focal animals for 15 months in La Esperanza,
      northeastern Peru. By use of combined data for all groups I examined the effects
      of season, activity, and age/sex class on nearest-neighbor distances and forest
      strata use. Small differences were observed for nearest-neighbor distances,
      forest strata use by different age/sex classes, and activity. Adult males had the
      lowest contact index scores. Contact index scores were low for juvenile females,
      for which nearest-neighbor distances were largest. Very little aggressive
      behavior was observed. Focal animals preferred upper levels of the forest with
      little difference in height for different activities. Lagothrix flavicauda have
      very cohesive groups with little seasonal or activity-dependent difference
      between nearest-neighbor distances or proximity. These results suggest that this
      species has less variable social organization and greater group cohesion than
      other Atelini. However, more studies are needed on other populations of L.
      flavicauda to better determine the species' social organization. Studies are also
      required to determine the extent to which dispersal times and kinship affect
      proximity, nearest-neighbor distances, and aggression.

PMID- 24906419
TI  - Comparison of complementary and alternative medicine with conventional mind-body
      therapies for chronic back pain: protocol for the Mind-body Approaches to Pain
      (MAP) randomized controlled trial.
AB  - BACKGROUND: The self-reported health and functional status of persons with back
      pain in the United States have declined in recent years, despite greatly
      increased medical expenditures due to this problem. Although patient psychosocial
      factors such as pain-related beliefs, thoughts and coping behaviors have been
      demonstrated to affect how well patients respond to treatments for back pain, few
      patients receive treatments that address these factors. Cognitive-behavioral
      therapy (CBT), which addresses psychosocial factors, has been found to be
      effective for back pain, but access to qualified therapists is limited. Another
      treatment option with potential for addressing psychosocial issues, mindfulness
      based stress reduction (MBSR), is increasingly available. MBSR has been found to
      be helpful for various mental and physical conditions, but it has not been well
      studied for application with chronic back pain patients. In this trial, we will
      seek to determine whether MBSR is an effective and cost-effective treatment
      option for persons with chronic back pain, compare its effectiveness and cost
      effectiveness compared with CBT and explore the psychosocial variables that may
      mediate the effects of MBSR and CBT on patient outcomes. METHODS/DESIGN: In this
      trial, we will randomize 397 adults with nonspecific chronic back pain to CBT,
      MBSR or usual care arms (99 per group). Both interventions will consist of eight
      weekly 2-hour group sessions supplemented by home practice. The MBSR protocol
      also includes an optional 6-hour retreat. Interviewers masked to treatment
      assignments will assess outcomes 5, 10, 26 and 52 weeks postrandomization. The
      primary outcomes will be pain-related functional limitations (based on the Roland
      Disability Questionnaire) and symptom bothersomeness (rated on a 0 to 10
      numerical rating scale) at 26 weeks. DISCUSSION: If MBSR is found to be an
      effective and cost-effective treatment option for patients with chronic back
      pain, it will become a valuable addition to the limited treatment options
      available to patients with significant psychosocial contributors to their pain.
      TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01467843.

PMID- 24906421
TI  - Congenic mice reveal genetic epistasis and overlapping disease loci for
      autoimmune diabetes and listeriosis.
AB  - The nonobese diabetic (NOD) mouse strain serves as a genomic standard for
      assessing how allelic variation for insulin-dependent diabetes (Idd) loci affects
      the development of autoimmune diabetes. We previously demonstrated that C57BL/6
      (B6) mice harbor a more diabetogenic allele than NOD mice for the Idd14 locus
      when introduced onto the NOD genetic background. New congenic NOD mouse strains,
      harboring smaller B6-derived intervals on chromosome 13, now localize Idd14 to an
      ~18-Mb interval and reveal a new locus, Idd31. Notably, the B6 allele for Idd31
      confers protection against diabetes, but only in the absence of the diabetogenic
      B6 allele for Idd14, indicating genetic epistasis between these two loci.
      Moreover, congenic mice that are more susceptible to diabetes are more resistant
      to Listeria monocytogenes infection. This result co-localizes Idd14 and Listr2, a
      resistance locus for listeriosis, to the same genomic interval and indicates that
      congenic NOD mice may also be useful for localizing resistance loci for
      infectious disease. 

PMID- 24906422
TI  - Pharmacokinetics of afatinib in subjects with mild or moderate hepatic
      impairment.
AB  - PURPOSE: Afatinib, an oral irreversible ErbB family blocker, undergoes minimal
      metabolism by non-enzyme-catalysed adduct formation with proteins or nucleophilic
      small molecules and is predominantly non-renally excreted via the entero-hepatic
      system. This trial assessed whether mild or moderate hepatic impairment
      influences the pharmacokinetics of afatinib. METHODS: This was an open-label
      single-dose study. Pharmacokinetic parameters after afatinib 50 mg were
      investigated in subjects with mild (n = 8) or moderate (n = 8) hepatic impairment
      (Child-Pugh A and B) and healthy controls (n = 16) matched for age, weight and
      gender. Plasma and urine samples for pharmacokinetic assessment were collected
      before and up to 10 days after dosing. Additional blood samples were drawn to
      determine ex vivo plasma protein binding of afatinib. Primary endpoints were
      comparisons of afatinib C max and AUC0-infinity between subjects with hepatic
      impairment and healthy matched controls. Study progression was based on drug
      related toxicity (CTCAE v. 3.0) and C max of afatinib. RESULTS: Afatinib
      pharmacokinetic profiles and plasma protein binding were similar in subjects with
      impaired liver function and healthy controls. Compared with matched controls, the
      afatinib-adjusted geometric mean ratio for AUC0-infinity was 92.6% (90% CI 68.0
      126.3%) and Cmax was 109.5% (90% CI 82.7-144.9%) for subjects with mild hepatic
      impairment, and 94.9% (90% CI 72.3-124.5%) and 126.9% (90% CI 86.0-187.2%),
      respectively, for subjects with moderate hepatic impairment. For all parameters,
      the 90% CI included 100%. Afatinib was generally well tolerated with no serious
      adverse events reported. CONCLUSION: Mild to moderate hepatic impairment had no
      clinically relevant effect on the pharmacokinetics of a single 50 mg dose of
      afatinib, implying that adjustments to the starting dose of afatinib are not
      considered necessary in this patient population.

PMID- 24906423
TI  - A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in
      patients with advanced non-small cell lung cancer.
AB  - PURPOSE: Genexol-PM is a Cremorphor EL (CrEL)-free polymeric micelle formulation
      of paclitaxel that allows higher-dose administration with less hypersensitivity.
      This study was designed to evaluate the efficacy and safety of Genexol-PM and
      gemcitabine combination in advanced non-small cell lung cancer patients as a
      first-line treatment. PATIENTS AND METHODS: This is a prospective, single-arm,
      single-center phase II study. Patients with advanced NSCLC received Genexol-PM at
      230 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on day 1 and day 8 of a 3-week
      cycle. Six cycles of chemotherapy were planned unless there was disease
      progression. The primary endpoint was overall response rate. RESULTS: Forty-three
      patients received the study drugs with a median of 4 cycles per patient (range 1
      6). The overall response rate was 46.5%. The median progression-free survival was
      4.0 months (95% CI 2.0-6.0 months), and median overall survival was 14.8 months
      (95% CI 9.1-20.5 months). The most common toxicities were anemia (n = 29, 67%),
      asthenia (n = 17, 40%), myalgia (n = 16, 37%), peripheral neuropathy (n = 15, 35
      %), and diarrhea (n = 12, 30%). The most common grade 3/4 adverse events were
      neutropenia (n = 7, 16%) and pneumonia (n = 5, 12%). Two patients died of
      pneumonia and dyspnea. CONCLUSIONS: CrEL-free paclitaxel in combination with
      gemcitabine demonstrated favorable antitumor activity with little emetogenicities
      in non-small cell lung cancer patients. However, frequent grade 3/4 toxicities
      were observed, and safety should be evaluated thoroughly in future studies.

PMID- 24906424
TI  - Comparison of novel risk factors for cardiovascular disease between hemodialysis
      patients with and without protein-energy wasting.
AB  - PURPOSE: The present study was designed to compare novel risk factors for
      cardiovascular diseases (CVD) between hemodialysis (HD) patients with or without
      protein-energy wasting (PEW) for determining novel risk factors for CVD in HD
      patients with PEW. METHODS: In this cross-sectional study, 291 HD patients were
      randomly selected from among 2,302 adult HD patients in Tehran hemodialysis
      centers. The presence of PEW in HD patients was determined by subjective global
      assessment. In addition, 4 mL blood was obtained before dialysis and analyzed for
      serum concentrations of novel risk factors for CVD, including C-reactive protein
      (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular
      cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA),
      nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)]. RESULTS: Serum CRP
      and sICAM-1 were significantly higher in HD patients with PEW as compared to
      those without PEW (P < 0.01), whereas there were no significant differences in
      serum sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a) between the two
      groups. Serum CRP and sICAM-1 were significantly higher in HD patients with PEW
      type IIa and IIb than in those with PEW type I (P < 0.01). CONCLUSION: The
      present study indicates that serum CRP and sICAM-1, as two CVD risk factors,
      increase in HD patients with PEW as compared to those without PEW and these
      increases occur in HD patients with PEW type IIa and IIb who have inflammation.

PMID- 24906425
TI  - Localised amyloidosis of the glans penis presenting as a painless lump with
      progression after 10 years.
AB  - Primary amyloidosis of the genitourinary tract is uncommon, and isolated invasion
      of the glans penis is exceptionally rare Degos et al. (Bull Soc Fr Dermatol
      Syphiligr 68:159, 1961). We report a case of localised amyloidosis of the glans
      penis in a 40-year-old presenting as an asymptomatic penile mass which changed
      after 10 years prompting treatment. We believe this to be the longest interval
      recorded between clinical occurrence and histological diagnosis of primary penile
      amyloidosis.

PMID- 24906426
TI  - Isolation and in vitro characterization of bovine amniotic fluid derived stem
      cells at different trimesters of pregnancy.
AB  - Amniotic fluid (AF) is a source of multipotent mesenchymal stem cells (MSCs),
      very promising cells for tissue engineering in clinical application. The aim of
      this work was to isolate and characterize cells isolated from bovine AF as
      alternative sources of primitive multipotent stem cells in a species that could
      be a large-animal model for biomedical and biotechnology researches. Samples were
      recovered, at slaughterhouse, from 39 pregnant cows at different trimesters of
      pregnancy and cells were cultured in vitro. At passages (P) 3 and 7
      differentiation towards chondrogenic, osteogenic and adipogenic lineages was
      induced. Flow cytometry analysis for CD90, CD105, CD73, CD44, CD34, CD45 and CD14
      was performed, immunocytochemistry (ICC) for Oct4, SSEA4, alpha-SMA, Vimentin, N-
      and E- Cadherin and CK and qPCR analysis for OCT4, NANOG and SOX2 were carried
      out. The cell yield was significantly higher in the first trimester compared to
      the second and the third one (P < 0.05). Cells were isolated from 25/39 samples
      and cell population appeared heterogeneous. Two main cell types were identified
      in samples from all trimesters: round- (RS) and spindle-shaped (SS) cells. 17/25
      samples showed both populations (mixed, MX). Both cell types showed MSC-markers
      and differentiation capability with some variability related to the passages. The
      SS-population also expressed low levels of stemness markers such as NANOG and
      SSEA4 but not OCT4. Bovine AF shows a heterogeneous cell population containing
      also MSCs, multipotent cells that represent an intermediate stage between
      embryonic stem cells and adult ones.

PMID- 24906427
TI  - Interspecific hybridization between greater kudu and nyala.
AB  - Hybridization of wildlife species, even in the absence of introgression, is of
      concern due to wasted reproductive effort and a reduction in productivity. In
      this study we detail an accidental mating between a female nyala (Tragelaphus
      angasii) and a male greater kudu (T. strepsiceros). The hybrid was phenotypically
      nyala and was identified as such based on mitochondrial DNA. Further genetic
      analysis based on nine microsatellite markers, chromosome number and chromosome
      morphology however, confirmed its status as an F1 hybrid. Results obtained from a
      reproductive potential assessment indicated that this animal does not have the
      potential to breed successfully and can be considered as sterile.

PMID- 24906428
TI  - A review on lipase-catalyzed reactions in ultrasound-assisted systems.
AB  - The named "green chemistry" has been receiving increasing prominence due to its
      environmentally friendly characteristics. The use of enzymes as catalysts in
      processes of synthesis to replace the traditional use of chemical catalysts
      present as main advantage the fact of following the principles of the green
      chemistry. However, processes of enzymatic nature generally provide lower yields
      when compared to the conventional chemical processes. Therefore, in the last
      years, the ultrasound has been extensively used in enzymatic processes, such as
      the production of esters with desirable characteristics for the pharmaceutical,
      cosmetics, and food industry, for the hydrolysis and glycerolysis of vegetable
      oils, production of biodiesel, etc. Several works found in the open literature
      suggest that the energy released by the ultrasound during the cavitation
      phenomena can be used to enhance mass transfer (substrate/enzyme), hence
      increasing the rate of products formation, and also contributing to enhance the
      enzyme catalytic activity. Furthermore, the ultrasound is considered a "green"
      technology due to its high efficiency, low instrumental requirement and
      significant reduction of the processing time in comparison to other techniques.
      The main goal of this review was to summarize studies available to date regarding
      the application of ultrasound in enzyme-catalyzed esterification, hydrolysis,
      glycerolysis and transesterification reactions. 

PMID- 24906429
TI  - Uniform step-by-step observer for aerobic bioreactor based on super-twisting
      algorithm.
AB  - This paper describes a fixed-time convergent step-by-step high order sliding mode
      observer for a certain type of aerobic bioreactor system. The observer was
      developed using a hierarchical structure based on a modified super-twisting
      algorithm. The modification included nonlinear gains of the output error that
      were used to prove uniform convergence of the estimation error. An energetic
      function similar to a Lyapunov one was used for proving the convergence between
      the observer and the bioreactor variables. A nonsmooth analysis was proposed to
      prove the fixed-time convergence of the observer states to the bioreactor
      variables. The observer was tested to solve the state estimation problem of an
      aerobic bioreactor described by the time evolution of biomass, substrate and
      dissolved oxygen. This last variable was used as the output information because
      it is feasible to measure it online by regular sensors. Numerical simulations
      showed the superior behavior of this observer compared to the one having linear
      output error injection terms (high-gain type) and one having an output injection
      obtaining first-order sliding mode structure. A set of numerical simulations was
      developed to demonstrate how the proposed observer served to estimate real
      information obtained from a real aerobic process with substrate inhibition. 

PMID- 24906431
TI  - False-positive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)
      findings of bone metastasis from esophagogastric cancer: report of two cases.
AB  - We report two cases of (18)F-fluorodeoxyglucose positron emission tomography
      computed tomography (FDG PET-CT) fusion imaging showing false-positive findings
      of bone metastases from esophagogastric cancer. Although multiple bone metastases
      from esophagogastric cancer were suggested by several images, ultimately,
      degeneration of the bone marrow was diagnosed histologically. We discuss the
      value of imaging modalities and the importance of a comprehensive diagnosis based
      on a combination of physical examination, laboratory test results, and imaging
      studies. 

PMID- 24906430
TI  - HITS-CLIP reveals key regulators of nuclear receptor signaling in breast cancer.
AB  - miRNAs regulate the expression of genes in both normal physiology and disease.
      While miRNAs have been demonstrated to play a pivotal role in aspects of cancer
      biology, these reports have generally focused on the regulation of single genes.
      Such single-gene approaches have significant limitations, relying on miRNA
      expression levels and heuristic predictions of mRNA-binding sites. This results
      in only circumstantial evidence of miRNA-target interaction and typically leads
      to large numbers of false positive predictions. Here, we used a genome-wide
      approach (high-throughput sequencing of RNA isolated by crosslinking
      immunoprecipitation, HITS-CLIP) to define direct miRNA-mRNA interactions in three
      breast cancer subtypes (estrogen receptor positive, Her2 amplified, and triple
      negative). Focusing on steroid receptor signaling, we identified two novel
      regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target
      multiple genes involved in ER signaling. Moreover, this approach enabled the
      definition of miR-9-5p as a global regulator of steroid receptor signaling in
      breast cancer. We show that miRNA targets and networks defined by HITS-CLIP under
      physiologic conditions are predictive of patient outcomes and provide global
      insight into miRNA regulation in breast cancer. 

PMID- 24906433
TI  - Part I: An anatomic-based tunnel in the fibular head for posterolateral corner
      reconstruction using magnetic resonance imaging.
AB  - PURPOSE: Currently, there are no studies that clearly define a method for the
      placement of the fibular tunnel between the fibular collateral ligament (FCL) and
      popliteofibular ligament (PFL) insertions when performing an anatomic-based
      posterolateral corner reconstruction. The purpose of this study was to use
      magnetic resonance-based anatomic landmarks to describe the orientation of a
      fibular tunnel between the FCL and PFL insertions. METHODS: Magnetic resonance
      imaging (MRI) of 105 patients with normal posterolateral corner knee anatomy was
      identified by a musculoskeletal radiologist, and the FCL and popliteofibular
      insertions were labelled. Three experienced providers independently evaluated the
      images. In the axial plane, the Cobb angle of a fibular tunnel from the FCL to
      the popliteofibular insertion was measured using the tibial tubercle as a
      reference. In the sagittal plane, the same tunnel was measured in reference to
      the lateral tibial plateau. RESULTS: In the axial plane, the average Cobb angle
      for an anatomic-based fibular tunnel was 48.1 degrees  +/- 10.7 degrees 
      (ICC(2,1) = 0.76, p < 0.01) externally rotated to the tibial tubercle. In the
      sagittal plane, the average Cobb angle for an anatomic-based fibular tunnel was
      59.8 degrees  +/- 11.9 degrees  (ICC(2,1) = 0.81, p < 0.01) cranial, referenced
      from the lateral tibial plateau. The average length of the fibular tunnel was 2.0
      +/- 0.4 cm (ICC(2,1) = 0.78, p < 0.01), at the point of the fibular insertion.
      The distance from the midpoint of the fibular tunnel to the posterolateral wall
      of the fibular head was 0.8 +/- 0.2 cm (ICC(2,1) = 0.63, p < 0.01). CONCLUSIONS:
      The results of this study suggest that MRI can be used to identify the
      orientation between the FCL and PFL insertions to create an anatomic-based
      fibular tunnel, which is 50 degrees  externally rotated from the tibial tubercle
      in the axial plane and placed in a cranial direction of 60 degrees  relative to
      the lateral joint line. The clinical relevance of this study is that this
      information may aid surgeons in placing a fibular tunnel connecting the FCL and
      PFL insertions. LEVEL OF EVIDENCE: IV.

PMID- 24906434
TI  - Foreseeing the danger in the beach chair position: Are standard measurement
      methods reliable?
AB  - PURPOSE: The aim of this study is to show whether peripheral perfusion monitoring
      methods reflect central perfusion during shoulder arthroscopy at beach chair
      position. We hypothesized that mean arterial pressure (MAP), central heart rate
      (CHR) and peripheral oxygenation (SaO2) measurements individually will not
      parallel cerebral oximetry measurements by near-infrared spectroscopy (NIRS).
      METHODS: Between 2011 and 2012, 53 patients who had arthroscopic rotator cuff
      repair surgery in the beach chair position were enrolled prospectively. Median
      ages of the patients were 58 (range 42-68) years. The regional cerebral oxygen
      saturation value of each hemisphere was continuously monitored by the use of
      NIRS. MAP, CHR, SaO2 and both hemispheric cerebral oxygen saturation values were
      recorded at six time periods peri-operatively. Correlation and differences
      between parameters were evaluated. RESULTS: Cerebral oxygen saturation of right
      hemisphere was dropped >20 % in 28.3 and 45.3 % of the patients. At left
      hemisphere, cerebral oxygen saturation was dropped >20 % in 20.8 and 43.4 % of
      the patients. Peripheral saturation values were statistically different from
      cerebral saturation values (p < 0.001). On the other hand, there was a
      correlation between cerebral saturation and MAP values (p < 0.05). CONCLUSION:
      Cerebral oximetry by NIRS may prove useful as a monitor for cerebral ischaemia.
      In the absence of NIRS, CHR can partially detect abnormalities but not trustable,
      and MAP is the most reliable method for monitoring.

PMID- 24906435
TI  - Does concomitant meniscectomy or meniscal repair affect the recovery of
      quadriceps function post-ACL reconstruction?
AB  - PURPOSE: The purpose of this study was to determine the effect of concomitant
      meniscal surgery on the recovery of quadriceps activation and strength at a time
      when individuals return to sport following anterior cruciate ligament (ACL)
      reconstruction. METHODS: Forty-six individuals that were cleared for
      participation following ACL reconstruction were invited to participate in this
      study. Participants were placed into groups according to surgical reports (ACL
      only, n = 24; meniscal repair, n = 12; meniscectomy, n = 10). Quadriceps strength
      was quantified using isokinetic and isometric measures. Isokinetic strength was
      collected at 60 degrees /s in concentric mode. Isometric strength was collected
      at 90 degrees  of knee flexion. Quadriceps activation was assessed using the
      burst superimposition technique and quantified via the central activation ratio.
      One-way ANOVAs were utilized to detect whether differences existed in quadriceps
      activation and strength between groups. Where appropriate, post hoc Bonferroni
      multiple comparison procedures were used. RESULTS: Quadriceps activation (P =
      n.s.) and strength (isokinetic: P = n.s.; isometric: P = n.s.) were not different
      between groups. CONCLUSION: Concomitant meniscectomy or meniscal repair did not
      affect the recovery of quadriceps activation and strength at a time when
      individuals return to sport following ACL reconstruction. Though group
      differences in quadriceps function were not detected, all participants
      demonstrated levels of quadriceps activation failure that are below healthy
      individuals at a time when they were returned to sport. Given that persistent
      quadriceps activation failure is detrimental to knee function, rehabilitation
      protocols that target quadriceps activation failure should be developed and
      employed post-reconstruction.

PMID- 24906436
TI  - [Early geriatric rehabilitation: an opportunity for the oldest old].
AB  - BACKGROUND: Physicians in Germany who are not specialized in geriatric medicine
      often have to make decisions regarding referral of patients for early geriatric
      rehabilitation. The risk of inadequate patient allocation is due to lack of
      knowledge or underestimation of the potential benefit of early rehabilitation in
      reducing a patient's need of care. Particularly the oldest old are affected by
      those inadequate decisions. MATERIALS AND METHODS: Based on the nationwide
      database Gemidas Pro, the data sets of >= 90-year-old patients were analysed
      regarding diagnoses, multimorbidity, gender, length of stay, procedures, outcome
      parameters as nursing personnel regulation (PPR), Barthel index and the Timed Up
      and Go (TUG) test compared to younger age groups. Data from 85 acute inpatient
      geriatric institutions during the period from January 2006 to December 2009 were
      included. RESULTS: Neither the analysis of the diagnosis nor multimorbidity
      showed relevant differences compared to younger patients. Despite poorer
      functional status at admission, the >= 90 year olds experienced a 25 % increase
      in the activities of daily living (ADL) measured by PPR, 30 % increase in
      mobility classification based on the TUG and 59 % increase in ADL measured with
      the Barthel index. These changes were significantly different. In addition, the
      length of stay was 18.96 days on average in the group of >= 90-year-old patients,
      which was but not significantly shorter than the length of stay in the group of
      70- to 79-year-old (19.7 days) and 80- to 89-year-old patients (19.65 days).
      CONCLUSION: The analyses show that the oldest old suffer from more severe
      deficits in functional status on admission in acute geriatric wards compared to
      younger patient groups. However, on discharge the oldest old show a significant
      and relevant increase in mobility and ADL without increase in length of stay.

PMID- 24906437
TI  - Ready conversion of patients with well-controlled, moderate to severe, chronic
      malignant tumor-related pain on other opioids to tapentadol extended release.
AB  - BACKGROUND AND OBJECTIVES: The effectiveness and tolerability of tapentadol
      extended release (ER), a centrally acting analgesic with MU-opioid receptor
      agonist and norepinephrine (noradrenaline) reuptake inhibitor activities, have
      been demonstrated in patients with chronic pain, including those switching
      directly from prior opioid therapy. The objective of the current study was to
      evaluate the effectiveness and safety of conversion to oral tapentadol ER (50-250
      mg twice daily) from previous around-the-clock strong opioid therapy in patients
      with moderate to severe, chronic malignant tumor-related cancer pain that was
      well-controlled. METHODS: This randomized, open-label, phase III study, which was
      conducted in Japan, included a 1- to 2-week screening period (on previous opioid)
      and an 8-week, open-label treatment period. Eligible patients, who were taking a
      strong opioid analgesic and had a mean pain intensity score <4 during the 3 days
      prior to randomization (adequate pain control on previous strong opioid), were
      randomized (1:1) to receive twice-daily treatment with tapentadol ER (100-500
      mg/day) or morphine sustained release (SR; 20-140 mg/day; reference for assay
      sensitivity). Initial doses were estimated based on the conversion ratio of
      tapentadol ER:oxycodone:morphine:fentanyl = 10:2:3:0.03. The primary
      effectiveness endpoint was the proportion of patients who maintained pain control
      [change from baseline in mean pain intensity (11-point numerical rating scale)
      less than +1.5 for 3 consecutive days and no more than two doses of rescue
      medication per day for 3 consecutive days) during the first week of open-label
      treatment. RESULTS: In the tapentadol ER group (n = 50), 84.0 % of patients
      (42/50; 95 % CI, 70.89-92.83) maintained pain control during Week 1. On the
      Patient Global Impression of Change, 2.1 % (1/48), 2.1 % (1/48), 22.9 % (11/48),
      and 50.0 % (24/48) of patients in the tapentadol ER group reported that their
      overall condition was "very much improved," "much improved," "minimally
      improved," and "not changed," respectively, at Week 1 compared with 0 %, 10.7 %
      (3/28), 28.6 % (8/28), and 53.6 % (15/28) reporting these ratings at Week 8. The
      sensitivity of effectiveness analyses was validated based on results using
      morphine SR; 98.0 % (49/50; 95 % CI, 89.35-99.95) of patients in the morphine SR
      group maintained pain control after 1 week of treatment. The overall safety
      profile was similar to that demonstrated in previous studies; tapentadol ER was
      associated with a lower incidence of gastrointestinal treatment-emergent adverse
      events than morphine SR [38.0 % (19/50) vs. 54.0 % (27/50)], including
      constipation [12.0 % (6/50) vs. 20.0 % (10/50)] and vomiting [6.0 % (3/50) vs.
      26.0 % (13/50)]. CONCLUSIONS: Overall, results indicate that conversion from
      previous strong opioids to tapentadol ER (50-250 mg twice daily) was successful
      and resulted in safe and effective pain control with improved gastrointestinal
      tolerability versus morphine SR in patients with moderate to severe cancer
      related pain that was well-controlled on their previous opioid.

PMID- 24906438
TI  - The overexpression of epithelial cell adhesion molecule (EpCAM) in glioma.
AB  - Epithelial cell adhesion molecule (EpCAM) is overexpressed in various neoplasms
      as a tumor-associated antigen and absent in natural brain. However, little is
      known about EpCAM's expression in gliomas. To investigate the expression of EpCAM
      in gliomas and understand the correlation of EpCAM expression with malignancy,
      proliferation, angiogenesis, and prognosis, we studied the expression of EpCAM in
      98 glioma samples by immunohistochemistry and by western blotting (N = 12).
      Correlative analysis of EpCAM overexpression with microvessel density (MVD), Ki
      67 expression, age, and gender were made. Survival data was analyzed with Kaplan
      Meier method and Cox Proportional Hazard Model. Immunohistochemistry results
      showed EpCAM was widely expressed in glioma (90.8 %). The overexpression rate of
      WHO grade IV gliomas was significantly higher EpCAM overexpression correlated
      significantly with Ki-67 expression and MVD. Western blot analysis also revealed
      a stepwise increase in EpCAM expression from WHO II to IV glioma. The overall
      survival of WHO III and IV glioma patients with EpCAM overexpression was
      obviously lower than that without EpCAM overexpression. EpCAM overexpression was
      an independent prognostic factor for overall survival in glioma patients. This
      study firstly shows that EpCAM overexpression correlates significantly with
      malignancy (WHO grades), proliferation (Ki67), angiogenesis (MVD), and prognosis
      in gliomas. EpCAM may participate in tumorgenesis of gliomas.

PMID- 24906439
TI  - Molecular and phenotypic characterization of multidrug-resistant Mycobacterium
      tuberculosis isolates resistant to kanamycin, amikacin, and capreomycin in China.
AB  - Although second-line anti-tuberculosis (TB) injectable drugs have been widely
      used to improve treatment outcomes of multidrug-resistant TB (MDR-TB), little is
      known about the prevalence and mechanism of second-line injectable drug
      resistance among MDR Mycobacterium tuberculosis isolates in China. Here, we found
      that 12.7 % (20/158) of isolates showed resistance to at least one second-line
      injectable drug among 158 MDR isolates. At the same time, there were 16 (10.1 %)
      strains resistant to kanamycin (KAN), 9 (5.7 %) to amikacin (AMK), and 12 (7.6 %)
      to capreomycin (CAP). In addition, our data revealed no significant difference in
      the drug resistance patterns for Beijing versus non-Beijing genotype strains (p >
      0.05). The most frequently observed mutation was A-to-G substitution at position
      1401 of the rrs gene, conferring high-level resistance to KAN and AMK, but had
      varying minimum inhibitory concentrations (MICs) for CAP. The mutations in the
      eis promoter and tlyA gene were responsible for low-level resistance to CAP. 83.3
      % of A1401G substitutions in the rrs gene was observed in Beijing genotype
      strains, while the difference was not significant (p = 0.157). Our data
      demonstrated that the hot-spot regions localized in the rrs gene serve as
      excellent markers for AMK, but is not a sensitive marker for KAN and CAP. In
      addition, the cross-resistance patterns and MICs differed among different genetic
      mutation types, which challenge the practice in China of generalizing resistance
      to AMK and CAP based on the resistance to KAN alone. Our findings suggested that
      the individualized drug susceptibility to three major second-line injectable
      drugs is essential in order to generate more effective treatment regimens for MDR
      patients.

PMID- 24906440
TI  - Characterization of the staphylococcal cassette chromosome mec insertion site in
      108 isolates lacking the mecA gene and identified as methicillin-resistant
      Staphylococcus aureus by the Xpert MRSA assay.
AB  - During a 3-year period, 848 patients were detected as carriers of methicillin
      resistant Staphylococcus aureus (MRSA) by the Xpert MRSA assay (Cepheid). Among
      them, 108 patients (12.7 %) were colonized with strains showing methicillin
      susceptible phenotypes and absence of the mecA gene, despite being positive with
      the rapid polymerase chain reaction (PCR) assay. DNA sequences of the
      staphylococcal cassette chromosome mec (SCCmec) insertion site of these "false
      positive" strains was determined by direct sequencing of the genomic DNA. More
      than half (53.7 %) of the strains had DNA sequences unrelated to either SCC or
      SCCmec and one-third had DNA sequences related to non-mec SCC. Only 10.2 % of the
      strains carried sequences related to SCCmec, suggesting that a sequence
      containing the mecA gene was lost from an SCCmec. These findings differ from the
      general idea that all methicillin-susceptible S. aureus having positive Xpert
      MRSA assay results are essentially MRSA that lost the mecA gene.

PMID- 24906441
TI  - Volumetric FDG-PET predicts overall and progression- free survival after 14 days
      of targeted therapy in metastatic renal cell carcinoma.
AB  - BACKGROUND: To determine whether changes in the metabolism of metastatic renal
      cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment
      with tyrosine kinase inhibitors can predict overall and progression- free patient
      survival. METHODS: Thirty-nine consecutive patients with mRCC were included
      prospectively and underwent PET examinations prior to and after 14 and 28 days of
      standard treatment with sunitinib (n=18), sorafenib (n=19) or pazopanib (n=2).
      The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion
      glycolysis and a positive response (defined as a 30% reduction) compared to
      overall and progression- free survival. RESULTS: Thirty-five patients with at
      least one metabolically active metastatic lesion prior to treatment underwent
      additional FDG-PET examinations after 14 (n=32) and/or 28 days (n=30) of
      treatment. Changes in either SULpeak or total lesion glycolysis were correlated
      to both progression-free and overall survival (for TLG2.5 responders, HR=0.38
      (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders,
      HR=0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders,
      HR=0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In
      contrast SUVmax response did not predict progression- free or overall survival
      (HR=0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively).
      CONCLUSIONS: Assessment of early changes in SULpeak and total lesion glycolysis
      undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly
      predict progression- free and overall survival in patients with mRCC.

PMID- 24906442
TI  - Large-effect pleiotropic or closely linked QTL segregate within and across ten US
      cattle breeds.
AB  - BACKGROUND: The availability of high-density SNP assays including the BovineSNP50
      (50 K) enables the identification of novel quantitative trait loci (QTL) and
      improvement of the resolution of the locations of previously mapped QTL. We
      performed a series of genome-wide association studies (GWAS) using 50 K genotypes
      scored in 18,274 animals from 10 US beef cattle breeds with observations for
      twelve body weights, calving ease and carcass traits. RESULTS: A total of 159
      large-effects QTL (defined as 1-Mb genome windows explaining more than 1% of
      additive genetic variance) were identified. In general, more QTL were identified
      in analyses with bigger sample sizes. Four large-effect pleiotropic or closely
      linked QTLs located on BTA6 at 37-42 Mb (primarily at 38 Mb), on BTA7 at 93 Mb,
      on BTA14 at 23-26 Mb (primarily at 25 Mb) and on BTA20 at 4 Mb were identified in
      more than one breed. Several breed-specific large-effect pleiotropic or closely
      linked QTL were also identified. Some identified QTL regions harbor genes known
      to have large effects on a variety of traits in cattle such as PLAG1 and MSTN and
      others harbor promising candidate genes including NCAPG, ARRDC3, ERGIC1,
      SH3PXD2B, HMGA2, MSRB3, LEMD3, TIGAR, SEPT7, and KIRREL3. Gene ontology analysis
      revealed that genes involved in ossification and in adipose tissue development
      were over-represented in the identified pleiotropic QTL. Also, the MAPK signaling
      pathway was identified as a common pathway affected by the genes located near the
      pleiotropic QTL. CONCLUSIONS: This largest GWAS ever performed in beef cattle,
      led us to discover several novel across-breed and breed-specific large-effect
      pleiotropic QTL that cumulatively account for a significant percentage of
      additive genetic variance (e.g. more than a third of additive genetic variance of
      birth and mature weights; and calving ease direct in Hereford). These results
      will improve our understanding of the biology of growth and body composition in
      cattle.

PMID- 24906443
TI  - Death associated protein kinase 2 is expressed in cortical interstitial cells of
      the mouse kidney.
AB  - BACKGROUND: DAPK2 is a pro-apoptotic protein kinase that associates with TGFbeta
      receptors. The homolog DAPK1 has been shown to mediate apoptosis in kidney
      injury. Expression databases indicate that DAPK2 is expressed in the kidney, and
      in this work we investigate the localization of renal DAPK2 expression and its
      role in the kidney. RESULTS: Immunostaining demonstrates DAPK2 expression in
      interstitial cells of the renal cortex including PDGFRbeta-positive pericytes and
      the CD73-positive erythropoietin-expressing fibroblast population.
      Tubulointerstitial fibrosis in experimental CKD arises directly from resident
      interstitial cells, and we therefore evaluated the expression of DAPK2 in the
      expanded interstitium of mice with kidney disease induced by chronic cisplatin
      administration. Expanded renal interstitium in these animals was negative for
      DAPK2 expression, but healthy areas of the kidney in which the tubular
      interstitium had not expanded expressed DAPK2 at levels similar to the uninjured
      control. Dapk2 null mice were generated to evaluate if DAPK2 is required for
      formation of the kidney, or its maintenance in the adult. Kidneys of Dapk2 null
      mice did not show overt malformations or age-related degeneration, but did show a
      slight increase in the number of interstitial fibroblasts. Differences were seen
      between Dapk2 null mice and wild type controls in the response to
      tubulointerstitial fibrosis caused by chronic cisplatin administration. Although
      mutant and wild type mice displayed comparable levels of alpha smooth muscle
      actin, interstitial proliferation and SMAD2 signaling, Dapk2 null mice showed
      reduced interstitial collagen accumulation. CONCLUSIONS: In the kidney, DAPK2 is
      strongly and specifically expressed in interstitial cells of the cortex,
      providing a useful marker for this important cell population. Dapk2 null mice are
      phenotypically normal under steady state conditions, but display some resistance
      to extracellular matrix deposition in experimental renal fibrosis indicating that
      DAPK2 plays a profibrotic role in kidney injury.

PMID- 24906444
TI  - OsMYB103L, an R2R3-MYB transcription factor, influences leaf rolling and
      mechanical strength in rice (Oryza sativa L.).
AB  - BACKGROUND: The shape of grass leaves possesses great value in both agronomy and
      developmental biology research. Leaf rolling is one of the important traits in
      rice (Oryza sativa L.) breeding. MYB transcription factors are one of the largest
      gene families and have important roles in plant development, metabolism and
      stress responses. However, little is known about their functions in rice.
      RESULTS: In this study, we report the functional characterization of a rice gene,
      OsMYB103L, which encodes an R2R3-MYB transcription factor. OsMYB103L was
      localized in the nucleus with transactivation activity. Overexpression of
      OsMYB103L in rice resulted in a rolled leaf phenotype. Further analyses showed
      that expression levels of several cellulose synthase genes (CESAs) were
      significantly increased, as was the cellulose content in OsMYB103L overexpressing
      lines. Knockdown of OsMYB103L by RNA interference led to a decreased level of
      cellulose content and reduced mechanical strength in leaves. Meanwhile, the
      expression levels of several CESA genes were decreased in these knockdown lines.
      CONCLUSIONS: These findings suggest that OsMYB103L may target CESA genes for
      regulation of cellulose synthesis and could potentially be engineered for
      desirable leaf shape and mechanical strength in rice.

PMID- 24906445
TI  - Neuromuscular control of goal-directed ankle movements differs for healthy
      children and adults.
AB  - PURPOSE: The purpose was to compare neuromuscular control of rapid ankle goal
      directed movements in healthy preadolescent children and young adults. METHODS:
      Ten young adults (20.0 +/- 0.9 years) and ten children (9.5 +/- 0.7 years)
      attempted to accurately match the peak displacement of the foot to a
      spatiotemporal target with an ankle dorsiflexion movement. The targeted
      displacement was 9 degrees  of ankle dorsiflexion, and the targeted time was 180
      ms. Surface electromyograms (EMGs) were recorded from the tibialis anterior (TA;
      agonist) and soleus (SOL; antagonist) muscles. Ankle movement control was
      quantified with endpoint accuracy and variability. The activation of the involved
      muscles was quantified with an EMG burst analysis. RESULTS: Children exhibited
      decreased endpoint accuracy and control compared with young adults, as indicated
      by greater endpoint errors (47.6 +/- 15.2 vs. 25.8 +/- 9.0%) and position
      variability (29.5 +/- 5.7 vs. 15.2 +/- 6.1 %). In addition, children exhibited
      differences in muscle activation, as evidenced by greater TA (53.2 +/- 19.1 vs.
      33.0 +/- 19.0%) and SOL (19.9 +/- 12.0 vs. 9.6 +/- 5.4%) amplitudes of EMG burst,
      shorter TA duration (251.3 +/- 43.6 vs. 296.1 +/- 27.6%), and greater variability
      in the activation of these muscles. The endpoint error (R (2) = 0.7) and position
      variability (R (2) = 0.67) were predicted from the TA burst amplitude variability
      and TA burst duration. CONCLUSION: The differences in muscle activation and
      deficient control of rapid goal-directed ankle movements exhibited by children
      are likely due to their incomplete development of higher centers.

PMID- 24906446
TI  - Sex differences in muscular load among house painters performing identical work
      tasks.
AB  - PURPOSE: The present study aimed to estimate possible differences in upper body
      muscular load between male and female house painters performing identical work
      tasks. Sex-related differences in muscular load may help explain why women, in
      general, have more musculoskeletal complaints than men. METHODS: In a laboratory
      setting, 16 male and 16 female house painters performed nine standardised work
      tasks common to house painters. Unilateral electromyography (EMG) recordings were
      obtained from the supraspinatus muscle by intramuscular electrodes and from the
      trapezius, extensor and flexor carpi radialis muscles by surface electrodes.
      Relative muscular loads in %EMGmax as well as exerted force in Newton, based on
      ramp calibrations, were assessed. Sex differences were tested using a mixed model
      approach. RESULTS: Women worked at about 50% higher relative muscular loads than
      men in the supraspinatus and forearm muscles at all percentiles and in all tasks.
      Women exerted about 30% less force in the trapezius muscle at the 50th
      percentile. CONCLUSIONS: Female house painters had a higher relative muscular
      load than their male colleagues without exerting more force. The effects of a
      higher relative muscular load accumulated over years of work may in part explain
      why musculoskeletal complaints in the upper body occur more frequently among
      women than men.

PMID- 24906448
TI  - Spontaneous resolution of pseudoaneurysm after zotarolimus-eluting stent
      implantation: imaging evidence at 13 months of follow-up.
AB  - Coronary pseudoaneurysm is a rare complication of percutaneous coronary
      intervention with a drug-eluting stent. Neither precise incidence of the
      complication has been known, nor there has been any established therapeutic
      approach for it. A 69-years-old male with effort angina underwent percutaneous
      coronary intervention to his left main coronary artery (LMCA). After pre
      dilatation with a balloon, Endeavor zotarolimus-eluting stent (E-ZES) was
      successfully implanted into the lesion that extended from his LMCA to left
      anterior descending artery. At 6 months after stenting, coronary angiography
      (CAG) and intravascular ultrasound (IVUS) revealed coronary pseudoaneurysm at the
      stented segment. Follow-up CAG at 13 months after stenting showed the spontaneous
      and complete resolution of the pseudoaneurysm. Subsequent IVUS, optical coherence
      tomography, and coronary angioscopy visualized complete neointimal coverage of
      stent struts. This is the first case report of E-ZES-related pseudoaneurysm with
      relatively rapid resolution. Our patient suggests that E-ZES might incidentally
      contribute to this favorable outcome.

PMID- 24906447
TI  - Irisin and FNDC5: effects of 12-week strength training, and relations to muscle
      phenotype and body mass composition in untrained women.
AB  - PURPOSE: To investigate the effects of strength training on abundances of irisin
      related biomarkers in skeletal muscle and blood of untrained young women, and
      their associations with body mass composition, muscle phenotype and levels of
      thyroid hormones. METHODS: Eighteen untrained women performed 12 weeks of
      progressive whole-body heavy strength training, with measurement of strength,
      body composition, expression of irisin-related genes (FNDC5 and PGC1alpha) in two
      different skeletal muscles, and levels of serum-irisin and -thyroid hormones,
      before and after the training intervention. RESULTS: The strength training
      intervention did not result in changes in serum-irisin or muscle FNDC5
      expression, despite considerable effects on strength, lean body mass (LBM) and
      skeletal muscle phenotype. Our data indicate that training affects irisin biology
      in a LBM-dependent manner. However, no association was found between steady-state
      serum-irisin or training-associated changes in serum-irisin and alterations in
      body composition. FNDC5 expression was higher in m.Biceps brachii than in
      m.Vastus lateralis, with individual expression levels being closely correlated,
      suggesting a systemic mode of transcriptional regulation. In pre-biopsies, FNDC5
      expression was correlated with proportions of aerobic muscle fibers, a
      relationship that disappeared in post-biopsies. No association was found between
      serum-thyroid hormones and FNDC5 expression or serum-irisin. CONCLUSION: No
      evidence was found for an effect of strength training on irisin biology in
      untrained women, though indications were found for a complex interrelationship
      between irisin, body mass composition and muscle phenotype. FNDC5 expression was
      closely associated with muscle fiber composition in untrained muscle.

PMID- 24906449
TI  - Coronary artery calcification as a new predictor of non-target lesion
      revascularization during the chronic phase after successful percutaneous coronary
      intervention.
AB  - In the drug-eluting stent era, the outcome of patients undergoing percutaneous
      coronary intervention (PCI) has remarkably improved. Nevertheless, non-target
      lesion revascularization (non-TLR) is often performed even after successful PCI
      and optimized medical therapy. This study aimed to determine the predictor of non
      TLR. In all, 125 consecutive patients with stable angina pectoris underwent
      intravascular ultrasound (IVUS)-guided PCI and were followed up for 3.3 +/- 0.5
      years. We performed oral glucose-tolerance tests in patients with no history of
      known diabetes mellitus (DM) to investigate glucose tolerance. To evaluate the
      severity of coronary artery calcification (CAC), we calculated CAC score by
      multiplying the arc (degree) with the length (mm) of the superficial calcium
      deposit detected by IVUS. Fourteen patients underwent non-TLR (non-TLR group);
      the remaining 111 did not (reference group). Glycosylated hemoglobin (HbA1c; %)
      and prevalence of known DM were similar in both groups, but the non-TLR group had
      higher fasting blood glucose (103 +/- 16 vs. 94 +/- 11 mg/dl, p = 0.04) and blood
      glucose (196 +/- 60 vs. 149 +/- 48 MUU/ml, p = 0.01) and insulin at 2 h (184 +/-
      241 vs. 67 +/- 49 MUU/ml, p < 0.01) than did the reference group. CAC score was
      significantly higher in the non-TLR group (788 +/- 585 vs. 403 +/- 466, p =
      0.01). Multiple logistic analysis indicated that CAC score is an independent
      predictor of non-TLR (p = 0.008). Non-TLR-free rate was significantly higher for
      patients with CAC score >=400 than for those with CAC score <400 (p = 0.01). Non
      TLR is associated with abnormal glucose tolerance and CAC score; CAC score is an
      independent predictor of non-TLR. Secondary prevention is especially important in
      patients with high CAC scores.

PMID- 24906450
TI  - Efficacy of a church-based lifestyle intervention programme to control high
      normal blood pressure and/or high normal blood glucose in church members: a
      randomized controlled trial in Pretoria, South Africa.
AB  - BACKGROUND: In persons 15 years and above in South Africa the prevalence of pre
      diabetes and diabetes has been estimated at 9.1% and 9.6%, respectively, and the
      prevalence of systolic prehypertension and hypertension, 38.2% and 24.6%,
      respectively. Elevated blood glucose and elevated blood pressure are prototype of
      preventable chronic cardiovascular disease risk factors.Lifestyle interventions
      have been shown to control high normal blood pressure and/or high normal blood
      glucose. METHODS/DESIGN: This study proposes to evaluate the efficacy of a
      community (church)-based lifestyle intervention programme to control high normal
      blood pressure and/or high normal blood glucose in church members in a randomized
      controlled trial in Gauteng, South Africa. The objectives are to: (1) measure non
      communicable diseases profile, including hypertension and diabetes, health
      behaviours, weight management and psychological distress of church members; (2)
      measure the reduction of blood glucose and blood pressure levels after the
      intervention; (3) prevent the development of impaired glucose tolerance; (4)
      compare health behaviours, weight management and psychological distress, blood
      glucose and blood pressure levels between intervention and control groups, and
      within group during 6, 12, 24 and 36 months during and post intervention. The
      study will use a group-randomized design, recruiting 300 church members from 12
      churches. Churches will be randomly assigned to experimental and control
      conditions. DISCUSSION: Lifestyle interventions may prevent from the development
      of high blood pressure and/or diabetes. The findings will impact public health
      and will enable the health ministry to formulate policy related to lifestyle
      interventions to control blood pressure and glucose. TRIAL REGISTRATION NUMBER:
      PACTR201105000297151.

PMID- 24906451
TI  - Separate pulmonary artery and vein magnetic resonance angiography by use of an
      arterial spin labeling method.
AB  - A separate pulmonary vein (PV) is difficult to depict with the commonly used
      bright-blood magnetic resonance angiography method. Until now, no study has
      described the depiction of peripheral PVs without the artery. Our purpose in this
      study was to develop an arterial spin labeling (ASL)-based magnetic resonance
      angiography sequence to depict the pulmonary artery (PA) and vein separately. We
      developed such a sequence by using two inversion recovery pulses. The first pulse
      was non-selective, and the second pulse was selective and was applied to the
      aorta and heart. All studies were conducted on a 1.5-T clinical magnetic
      resonance system with six different inversion times for seven healthy volunteers.
      For evaluation, we categorized the inversion times by using visual scoring. Then,
      we used the magnitude image to evaluate the PA, and we used the real image to
      evaluate the PV. For the PA, an inversion time of 300 ms had the lowest score
      (1.43), and the score changed with increasing times; an inversion time of 1,100
      ms had the highest score (3.85). For the PV, an inversion time of 300 ms had the
      highest score (2.68), and the score decreased with increasing times. The results
      indicated that the PA and vein could be depicted separately by the use of an ASL
      based magnetic resonance angiography method. The optimal inversion times for the
      PV and artery were 300 and 1,100 ms, respectively.

PMID- 24906452
TI  - Card-placing test in amnestic mild cognitive impairment and its neural
      correlates.
AB  - BACKGROUND: [corrected] We investigated anatomical correlates of the card-placing
      test (CPT) in patients with amnestic mild cognitive impairment (aMCI). METHODS:
      Fifteen aMCI patients underwent part A and part B of the CPT and FDG-PET. The CPT
      scores and MMSE scores of 29 cognitively normal people were used for comparison.
      Statistical parametric mapping (SPM) correlation analysis was used to extract the
      regions whose changes in regional cerebral metabolism correlated significantly
      with part A and B of the CPT with adjustment of age, education and sex of
      patients. RESULTS: The aMCI patients had significantly lower MMSE scores (26.0 +/
      2.0 vs. 28.2 +/- 1.4, p < 0.001), CPT A (25.5 +/- 3.5 vs. 27.7 +/- 2.7, p =
      0.026) and CPT B scores (16.3 +/- 4.4 vs. 19.7 +/- 3.7, p = 0.011) compared to
      the normal population. The test scores of part B of the CPT correlated well with
      hypometabolism of the posterior cingulate gyrus and precuneus. CONCLUSIONS: This
      study suggests that the CPT B may reflect the functional status of the posterior
      cingulate gyrus in patients with aMCI.

PMID- 24906453
TI  - The LRP6 rs2302685 polymorphism is associated with increased risk of myocardial
      infarction.
AB  - BACKGROUND: Abnormal lipids is one of the critical risk factors for myocardial
      infarction (MI), however the role of genetic variants in lipid metabolism-related
      genes on MI pathogenesis still requires further investigation. We herein
      genotyped three SNPs (LRP6 rs2302685, LDLRAP1 rs6687605, SOAT1 rs13306731) in
      lipid metabolism-related genes, aimed to shed light on the influence of these
      SNPs on individual susceptibility to MI. METHODS: Genotyping of the three SNPs
      (rs2302685, rs6687605 and rs13306731) was performed in 285 MI cases and 650
      control subjects using polymerase chain reaction-ligation detection reaction (PCR
      LDR) method. The association of these SNPs with MI and lipid profiles was
      performed with SPSS software. RESULTS: Multivariate logistic regression analysis
      showed that C allele (OR = 1.62, P = 0.039) and the combined CT/CC genotype (OR =
      1.67, P = 0.035) of LRP6 rs2302685 were associated with increased MI risk, while
      the other two SNPs had no significant effect. Further stratified analysis
      uncovered a more evident association with MI risk among younger subjects (<=60
      years old). Fascinatingly, CT/CC genotype of rs2302685 conferred increased LDL-C
      levels compared to TT genotype (3.0 mmol/L vs 2.72 mmol/L) in younger subjects.
      CONCLUSIONS: Our data provides the first evidence that LRP6 rs2302685
      polymorphism is associated with an increased risk of MI in Chinese subjects, and
      the association is more evident among younger individuals, which probably due to
      the elevated LDL-C levels.

PMID- 24906454
TI  - Investigating the clinical significance of twinkling artifacts in patients with
      urolithiasis smaller than 5 mm.
AB  - PURPOSE: Our aim was to evaluate the effectiveness of twinkling artifacts (TA) in
      detecting calculi <5 mm in diameter in patients with renal colic pain who had
      undergone urinary grayscale ultrasonography (US) and computed tomography (CT)
      imaging assays. MATERIALS AND METHODS: In this retrospective study, a total of 76
      calculi <5 mm detected in 60 patients were evaluated. Whole data were established
      using an ultrasound (US) probe at frequencies 1.5-4.5 MHz and noncontrast CT. In
      US, echogenicity and posterior-shadow (PS) parameters were evaluated and compared
      with color-Doppler ultrasonography (CDUS) and CT signs. RESULTS: The mean size of
      measured calculi was 3.9 +/- 0.8 mm (range 2-5 mm). The calculus localization
      rates detected by CT imaging were as follows: kidneys (n = 61, 80.3 %), proximal
      ureter (n = 4, 5.3 %), middle ureter (n = 3, 3.9 %) and distal ureter (n = 8,
      10.5 %). CT detected the calculus in all 76 cases. There was a statistically
      significant difference in US-CT and CDUS-CT comparisons (p < 0.001 and p = 0.023,
      respectively); however, no difference was found when comparing both US methods
      with CT (p = 0.083). CONCLUSIONS: TA can be regarded as a significant marker of
      urolithiasis, and co-operative usage of Doppler and grayscale methods can yield
      satisfactory results comparable with CT.

PMID- 24906455
TI  - The antimicrobial effects of selenium nanoparticle-enriched probiotics and their
      fermented broth against Candida albicans.
AB  - BACKGROUND: Lactic acid bacteria are considered important probiotics for
      prevention of some infections. The aim of this work was to investigate the effect
      of selenium dioxide on the antifungal activity of Lactobacillus plantarum and L.
      johnsonii against Candida albicans. METHODS: Lactobacillus plantarum and L.
      johnsonii cells, grown in the presence and absence of selenium dioxide, and their
      cell-free spent culture media were tested for antifungal activity against C.
      albicans ATCC 14053 by a hole-plate diffusion method and a time-kill assay.
      RESULTS: Both L. plantarum and L. johnsonii reduced selenium dioxide to cell
      associated elemental selenium nanoparticles. The cell-free spent culture media,
      from both Lactobacillus species that had been grown with selenium dioxide for 48
      h, showed enhanced antifungal activity against C. albicans. Enhanced antifungal
      activity of cell biomass against C. albicans was also observed in cultures grown
      with selenium dioxide. CONCLUSIONS: Selenium dioxide-treated Lactobacillus spp.
      or their cell-free spent broth inhibited the growth of C. albicans and should be
      investigated for possible use in anti-Candida probiotic formulations in future.

PMID- 24906456
TI  - Activation of the EGFR/p38/JNK pathway by mitochondrial-derived hydrogen peroxide
      contributes to oxygen-induced contraction of ductus arteriosus.
AB  - Oxygen-induced contraction of the ductus arteriosus (DA) involves a mitochondrial
      oxygen sensor, which signals pO2 in the DA smooth muscle cell (DASMC) by
      increasing production of diffusible hydrogen peroxide (H2O2). H2O2 stimulates
      vasoconstriction by regulating ion channels and Rho kinase, leading to calcium
      influx and calcium sensitization. Because epidermal growth factor receptor (EGFR)
      signaling is also redox regulated and participates in oxygen sensing and
      vasoconstriction in other systems, we explored the role of the EGFR and its
      signaling cascade (p38 and c-Jun N-amino-terminal kinase (JNK)) in DA
      contraction. Experiments were performed in DA rings isolated from full-term New
      Zealand white rabbits and human DASMC. In human DASMCs, increasing pO2 from
      hypoxia to normoxia (40 to 100 mmHg) significantly increased cytosolic calcium, p
      < 0.01. This normoxic rise in intracellular calcium was mimicked by EGF and
      inhibited by EGFR siRNA. In DA rings, EGF caused contraction while the specific
      EGFR inhibitor (AG1478) and the tyrosine kinase inhibitors (genistein or
      tyrphostin A23) selectively attenuated oxygen-induced contraction (p < 0.01).
      Conversely, orthovanadate, a tyrosine phosphatase inhibitor known to activate
      EGFR signaling, caused dose-dependent contraction of hypoxic DA and superimposed
      increases in oxygen caused minimal additional contraction. Anisomycin, an
      activator of EGFR's downstream kinases, p38 and JNK, caused DA contraction;
      conversely, oxygen-induced DA contraction was blocked by inhibitors of p38
      mitogen-activated protein kinases (MAPK) (SB203580) or JNK (JNK inhibitor II). O2
      induced phosphorylation of EGFR occurred within 5 min of increasing pO2 and was
      inhibited by mitochondrial-targeted overexpression of catalase. AG1478 prevented
      the oxygen-induced p38 and JNK phosphorylation. In conclusion, O2-induced EGFR
      transactivation initiates p38/JNK-mediated increases in cytosolic calcium and
      contributes to DA contraction. The EGFR/p38/JNK pathway is regulated by
      mitochondrial redox signaling and is a promising therapeutic target for
      modulation of the patent ductus arteriosus. KEY MESSAGES: Oxygen activates
      epidermal growth factor receptor (EGFR) in ductus arteriosus (DA) smooth muscle
      cells. EGFR inhibition selectively attenuates O2-induced DA constriction. pO2
      induced EGFR activation is mediated by mitochondrial-derived hydrogen peroxide.
      p38 MAPK and JNK mediated EGFR's effects on oxygen-induced DA contraction.
      Tyrosine kinases and phosphatases participate in oxygen sensing in the DA. The
      EGFR pathway offers new therapeutic targets to modulate patency of the ductus
      arteriosus.

PMID- 24906457
TI  - Glycolytic genes in cancer cells are more than glucose metabolic regulators.
AB  - Nearly a hundred years of scientific research has revealed a notable preference
      of cancer cells to utilize aerobic glycolysis rather than mitochondrial oxidative
      phosphorylation for glucose-dependent ATP production, which is thought to be the
      root of tumor formation and growth. Glycolysis is a complex biochemical process
      that is mediated by multiple glycolytic genes. Besides regulating glucose
      metabolism, these genes are also suggested to possess various other functions
      related to cancer, including roles in cancer development and promotion,
      inhibition of apoptosis, cell cycle progression, and tumor metastasis. This
      article highlights the biological functions of glycolytic genes beyond their role
      in regulation of glycolysis and discusses their clinical implications, especially
      in regard to the use of glycolytic genes as biomarkers for early detection of
      cancer or as targets for novel anticancer treatments. 

PMID- 24906458
TI  - Growth factor transduction pathways: paradigm of anti-neoplastic targeted
      therapy.
AB  - Molecularly targeted cancer treatment has become an achievable goal thanks to
      systematic analysis of cancer genome as well as development of highly selective
      tumor targeted drugs. In many human cancers, deregulation of the RTK/RAS/MAPK
      pathway is the driving force of the disease. Indeed, cancer cells become addicted
      to such signaling, rendering them susceptible to drugs that can intercept growth
      factor signaling cascade at different levels. Discovery of mutations or aberrant
      expression of components of this cascade in radio- and chemotherapy refractory
      human melanoma acted as an enormous stimulus for scientist to try to identify and
      clinically test new therapeutic approaches blocking the RTK/RAS/MAPK cascade.
      These efforts not only resulted in the identification of new drugs for melanoma
      treatment but also in a better understanding of molecular basis of primary and
      secondary resistance to targeted therapies. 

PMID- 24906460
TI  - Percutaneous bone cement refixation of aseptically loose hip prostheses: the
      effect of interface tissue removal on injected cement volumes.
AB  - OBJECTIVE: To quantify whether injected cement volumes differed between two
      groups of patients who underwent experimental minimally invasive percutaneous
      cement injection procedures to stabilize aseptically loose hip prostheses. One
      patient group was preoperatively treated using gene-directed enzyme prodrug
      therapy to remove fibrous interface tissue, while the other group received no
      preoperative treatment. It was hypothesized that cement penetration may have been
      inhibited by the presence of fibrous interface tissue in periprosthetic lesions.
      MATERIALS AND METHODS: We analyzed 17 patients (14 female, 3 male, ages 72-91,
      ASA categories 2-4) who were treated at our institution. Osteolytic lesions and
      injected cement were manually delineated using 3D CT image segmentation, and the
      deposition of injected cement was quantified. RESULTS: Patients who underwent
      preoperative gene-directed enzyme therapy to remove fibrous tissue exhibited
      larger injected cement volumes than those who did not. The observed median
      increase in injected cement volume was 6.8 ml. Higher cement leakage volumes were
      also observed for this group. CONCLUSION: We conclude that prior removal of
      periprosthetic fibrous interface tissue may enable better cement flow and
      penetration. This might lead to better refixation of aseptically loosened
      prostheses.

PMID- 24906461
TI  - The impact of self-concept and college involvement on the first-year success of
      medical students in China.
AB  - Students' first-year academic success plays a critical role on their overall
      development in college, which implies the need to concentrate on identifying ways
      to improve students' first-year academic success. Different from most research on
      the subject, this study attempted to combine the sociological perspective of
      college impact with a psychological perspective to synthetically explore the
      causal relationship of specific types of self-concept and college involvement
      with academic success of medical students. A longitudinal study was conducted
      using 519 matriculates at a medical university in mainland China. We conducted
      the Cooperative Institutional Research Program freshmen survey and the Your First
      College Year survey to collect data of the pre-college and college academic and
      social self-concept, college involvement components, and some input
      characteristics. The academic success was measured by the first-year grade point
      average. A pathway analysis was conducted and showed the following results.
      Having high academic self-concept, being engaged in class and putting effort in
      homework or study directly contributes to increasing college achievement.
      Students' pre-college achievement and self-concept, faculty interaction, and
      homework involvement positively affected students' college academic self-concept
      development, which indirectly improved average grade point. These findings
      contribute to our understanding of a student's ability to interact with his or
      her collegiate environment and to experience academic success. 

PMID- 24906459
TI  - Examination of mechanisms (E-MECHANIC) of exercise-induced weight compensation:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Weight loss induced only by exercise is frequently less than
      expected, possibly because of compensatory changes in energy intake and/or energy
      expenditure. The purpose of the Examination of Mechanisms (E-MECHANIC) of
      Exercise-Induced Weight Compensation trial is to examine whether increased energy
      intake and/or reduced spontaneous activity or energy expenditure (outside of
      structured exercise) account for the less than expected, exercise-associated
      weight loss. METHODS/DESIGN: E-MECHANIC is a three-arm, 6-month randomized
      (1:1:1) controlled trial. The two intervention arms are exercise doses that
      reflect current recommendations for (1) general health (8 kcal/kg body weight per
      week (8 KKW), about 900 kcal/wk) and (2) weight loss (20 KKW, about 2,250
      kcal/wk). The third arm, a nonexercise control group, will receive health
      information only. The sample will include a combined total of 198sedentary,
      overweight or obese (body mass index: >=25 kg/m2 to <=45 kg/m2) men and women
      ages 18 to 65 years. The exercise dose will be supervised and tightly controlled
      in an exercise training laboratory. The primary outcome variables are energy
      intake, which will be measured using doubly labeled water (adjusted for change in
      energy stores) and laboratory-based food intake tests, and the discrepancy
      between expected weight loss and observed weight loss. Secondary outcomes include
      changes in resting metabolic rate (adjusted for change in body mass), activity
      levels (excluding structured exercise) and body composition. In an effort to
      guide the development of future interventions, the participants will be
      behaviorally phenotyped and defined as those who do compensate (that is, fail to
      lose the amount of weight expected) or do not compensate (that is, lose the
      amount of weight expected or more). DISCUSSION: In this study, we will attempt to
      identify underlying mechanisms to explain why exercise elicits less weight loss
      than expected. This information will guide the development of interventions to
      increase exercise-induced weight loss and maximize weight loss retention and
      related health benefits. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01264406
      (registration date: 20 December 2010).

PMID- 24906462
TI  - Barriers to the uptake and use of feedback in the context of summative
      assessment.
AB  - Despite calls for feedback to be incorporated in all assessments, a dichotomy
      exists between formative and summative assessments. When feedback is provided in
      a summative context, it is not always used effectively by learners. In this study
      we explored the reasons for this. We conducted individual interviews with 17
      students who had recently received web based feedback following a summative
      assessment. Constant comparative analysis was conducted for recurring themes. The
      summative assessment culture, with a focus on avoiding failure, was a dominant
      and negative influence on the use of feedback. Strong emotions were prevalent
      throughout the period of assessment and feedback, which reinforced the focus on
      the need to pass, rather than excel. These affective factors were heightened by
      interactions with others. The influence of prior learning experiences affected
      expectations about achievement and the need to use feedback. The summative
      assessment and subsequent feedback appeared disconnected from future clinical
      workplace learning. Socio-cultural influences and barriers to feedback need to be
      understood before attempting to provide feedback after all assessments. A move
      away from the summative assessment culture may be needed in order to maximise the
      learning potential of assessments. 

PMID- 24906463
TI  - Inequalities in child mortality in ten major African cities.
AB  - BACKGROUND: The existence of socio-economic inequalities in child mortality is
      well documented. African cities grow faster than cities in most other regions of
      the world; and inequalities in African cities are thought to be particularly
      large. Revealing health-related inequalities is essential in order for
      governments to be able to act against them. This study aimed to systematically
      compare inequalities in child mortality across 10 major African cities (Cairo,
      Lagos, Kinshasa, Luanda, Abidjan, Dar es Salaam, Nairobi, Dakar, Addis Ababa,
      Accra), and to investigate trends in such inequalities over time. METHODS: Data
      from two rounds of demographic and health surveys (DHS) were used for this study
      (if available): one from around the year 2000 and one from between 2007 and 2011.
      Child mortality rates within cities were calculated by population wealth
      quintiles. Inequality in child mortality was assessed by computing two measures
      of relative inequality (the rate ratio and the concentration index) and two
      measures of absolute inequality (the difference and the Erreyger's index).
      RESULTS: Mean child mortality rates ranged from about 39 deaths per 1,000 live
      births in Cairo (2008) to about 107 deaths per 1,000 live births in Dar es Salaam
      (2010). Significant inequalities were found in Kinshasa, Luanda, Abidjan, and
      Addis Ababa in the most recent survey. The difference between the poorest
      quintile and the richest quintile was as much as 108 deaths per 1,000 live births
      (95% confidence interval 55 to 166) in Abidjan in 2011-2012. When comparing
      inequalities across cities or over time, confidence intervals of all measures
      almost always overlap. Nevertheless, inequalities appear to have increased in
      Abidjan, while they appear to have decreased in Cairo, Lagos, Dar es Salaam,
      Nairobi and Dakar. CONCLUSIONS: Considerable inequalities exist in almost all
      cities but the level of inequalities and their development over time appear to
      differ across cities. This implies that inequalities are amenable to policy
      interventions and that it is worth investigating why inequalities are higher in
      one city than in another. However, larger samples are needed in order to improve
      the certainty of our results. Currently available data samples from DHS are too
      small to reliably quantify the level of inequalities within cities.

PMID- 24906464
TI  - Revisiting the mesosome as a novel site of hydrogen peroxide accumulation in
      Escherichia coli.
AB  - The major source of endogenous hydrogen peroxide is generally thought to be the
      respiratory chain of bacteria and mitochondria. In our previous works, mesosome
      structure was induced in cells during rifampicin effect, and the mesosome
      formation is always accompanied by excess hydrogen peroxide accumulation in
      bacterial cells. However, the underlying mechanisms of hydrogen peroxide
      production and the rationale behind it remain still unknown. Here we report that
      hydrogen peroxide can specifically accumulate in the mesosome in vitro. Mesosomes
      were interpreted earlier as artifacts of specific cells under stress through TEM
      preparation, while, in the current study, mesosomes were shown as intracellular
      compartments with specific roles and features by using quickly freezing
      preparation of TEM. Formation of hydrogen peroxide was observed in suspension of
      mesosomal vesicles by using either a fluorescence-based reporter assay or a
      histochemical method, respectively. Our investigation provides experimental
      evidence that mesosomes can be a novel site of hydrogen peroxide accumulation. 

PMID- 24906465
TI  - Construction and characterization of a thermostable whole-cell chitinolytic
      enzyme using yeast surface display.
AB  - To develop a novel yeast whole-cell biocatalyst by yeast surface display
      technology that can hydrolyze chitin, the chitinaseC gene from Serratia
      marcescens AS1.1652 strain was cloned and subcloned into the yeast surface
      display plasmid pYD1, and the recombinant plasmid pYD1/SmchiC was electroporated
      into Saccharomyces cerevisiae EBY100 cell. Aga2p-SmChiC fusion protein was
      expressed and anchored on the yeast cell surface by induction with galactose,
      which was verified by indirect immunofluorescence and Western blotting. The
      chitinolytic activity of the yeast whole-cell biocatalyst or partially purified
      enzyme was detected by agar plate clear zone test, SDS-PAGE zymography and
      dinitrosalicylic acid method. The results showed that the chitinaseC gene from S.
      marcescens AS1.1652 strain was successfully cloned and expressed on the yeast
      cell surface, Aga2p-SmChiC fusion protein with molecular weight (67 kDa) was
      determined. Tests on the effect of temperature and pH on enzyme activity and
      stability revealed that the yeast whole-cell biocatalyst and partially purified
      enzyme possessed both thermal stability and activity, and even maintained some
      activity under acidic and weakly alkaline conditions. The optimum reaction
      temperature and pH value were set at 52  degrees C and 5.0, respectively. Yeast
      surface display technology succeeded in preparing a yeast whole-cell biocatalyst
      with chitinolytic activity, and the utilization of chitin could benefit from this
      process of enzyme preparation.

PMID- 24906466
TI  - Resource estimation in high performance medical image computing.
AB  - Medical imaging analysis processes often involve the concatenation of many steps
      (e.g., multi-stage scripts) to integrate and realize advancements from image
      acquisition, image processing, and computational analysis. With the dramatic
      increase in data size for medical imaging studies (e.g., improved resolution,
      higher throughput acquisition, shared databases), interesting study designs are
      becoming intractable or impractical on individual workstations and servers.
      Modern pipeline environments provide control structures to distribute
      computational load in high performance computing (HPC) environments. However,
      high performance computing environments are often shared resources, and
      scheduling computation across these resources necessitates higher level modeling
      of resource utilization. Submission of 'jobs' requires an estimate of the CPU
      runtime and memory usage. The resource requirements for medical image processing
      algorithms are difficult to predict since the requirements can vary greatly
      between different machines, different execution instances, and different data
      inputs. Poor resource estimates can lead to wasted resources in high performance
      environments due to incomplete executions and extended queue wait times. Hence,
      resource estimation is becoming a major hurdle for medical image processing
      algorithms to efficiently leverage high performance computing environments.
      Herein, we present our implementation of a resource estimation system to overcome
      these difficulties and ultimately provide users with the ability to more
      efficiently utilize high performance computing resources. 

PMID- 24906467
TI  - The normative range for and age and gender effects on the Sydney Swallow
      Questionnaire (SSQ).
AB  - The Sydney Swallow Questionnaire (SSQ) is a validated measure of the symptomatic
      severity of oral-pharyngeal dysphagia. Up until now no normative ranges have been
      established for the questionnaire. This is a limitation in its utility as it
      makes it difficult to use the tool to identify the prevalence and burden of oral
      pharyngeal dysphagia in the general population or within patient populations. The
      study's aim was to derive the normative range of dysphagia scores for the SSQ and
      to determine whether, in nondysphagic individuals, there are any age or gender
      effects on these scores. The questionnaire was administered to 73 eligible
      nondysphagic individuals who had been screened for any dysphagia or conditions
      that might predispose them to dysphagia. The frequency distribution of SSQ scores
      was first examined for normality and appropriate transformations performed before
      determining the upper limit of normal. Of the 73 healthy participants, 45 were
      male, and the cohort had a mean age of 58.6 years (range = 22.0-82.1 years). No
      statistically significant relationship between SSQ scores and either age (r s[73]
      = 0.140, p = 0.239) or gender (r pb[73] = 0.021, p = 0.857) was found. The mean
      total SSQ score (maximum possible score = 1,700) was 59.0 (SD = 56.7; range = 2
      241). The frequency distribution of scores was non-normal and markedly skewed.
      After a Box-Cox transformation to normalise the distribution, the calculated
      upper limit of the reference interval was 234 with a 90 % CI of [193, 277]. The
      SSQ scores in a nondysphagic population are not influenced by age or gender.
      These data complement the existing reliability and validation data and thereby
      improve the overall utility of the SSQ in the context of future studies of oral
      pharyngeal dysphagia prevalence, efficacy, and outcome. 

PMID- 24906469
TI  - Formation of blood clot on biomaterial implants influences bone healing.
AB  - The first step in bone healing is forming a blood clot at injured bones. During
      bone implantation, biomaterials unavoidably come into direct contact with blood,
      leading to a blood clot formation on its surface prior to bone regeneration.
      Despite both situations being similar in forming a blood clot at the defect site,
      most research in bone tissue engineering virtually ignores the important role of
      a blood clot in supporting healing. Dental implantology has long demonstrated
      that the fibrin structure and cellular content of a peri-implant clot can greatly
      affect osteoconduction and de novo bone formation on implant surfaces. This
      article reviews the formation of a blood clot during bone healing in relation to
      the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are
      dramatically altered from a normal clot in healing, resulting in conflicting
      effect on bone regeneration. These results indicate that the effect of clots on
      bone regeneration depends on how the clots are formed. Factors that influence
      blood clot structure and properties in relation to bone healing are also
      highlighted. Such knowledge is essential for developing strategies to optimally
      control blood clot formation, which ultimately alter the healing microenvironment
      of bone. Of particular interest are modification of surface chemistry of
      biomaterials, which displays functional groups at varied composition for the
      purpose of tailoring blood coagulation activation, resultant clot fibrin
      architecture, rigidity, susceptibility to lysis, and growth factor release. This
      opens new scope of in situ blood clot modification as a promising approach in
      accelerating and controlling bone regeneration. 

PMID- 24906468
TI  - Deuterium-substituted L-DOPA displays increased behavioral potency and dopamine
      output in an animal model of Parkinson's disease: comparison with the effects
      produced by L-DOPA and an MAO-B inhibitor.
AB  - The most effective treatment of Parkinson's disease (PD) L-DOPA is associated
      with major side effects, in particular L-DOPA-induced dyskinesia, which motivates
      development of new treatment strategies. We have previously shown that chronic
      treatment with a substantially lower dose of deuterium-substituted L-DOPA (D3-L
      DOPA), compared with L-DOPA, produced equal anti-parkinsonian effect and reduced
      dyskinesia in 6-OHDA-lesioned rats. The advantageous effects of D3-L-DOPA are in
      all probability related to a reduced metabolism of deuterium dopamine by the
      enzyme monoamine oxidase (MAO). Therefore, a comparative neurochemical analysis
      was here performed studying the effects of D3-L-DOPA and L-DOPA on dopamine
      output and metabolism in 6-OHDA-lesioned animals using in vivo microdialysis. The
      effects produced by D3-L-DOPA and L-DOPA alone were additionally compared with
      those elicited when the drugs were combined with the MAO-B inhibitor selegiline,
      used in PD treatment. The different treatment combinations were first evaluated
      for motor activation; here the increased potency of D3-L-DOPA, as compared to
      that of L-DOPA, was confirmed and shown to be of equal magnitude as the effect
      produced by the combination of selegiline/L-DOPA. The extracellular levels of
      dopamine were also increased following both D3-L-DOPA and selegiline/L-DOPA
      administration compared with L-DOPA administration. The enhanced behavioral and
      neurochemical effects produced by D3-L-DOPA and the combination of selegiline/L
      DOPA are attributed to decreased metabolism of released dopamine by MAO-B. The
      similar effect produced by D3-L-DOPA and selegiline/L-DOPA, respectively, is of
      considerable clinical interest since D3-L-DOPA, previously shown to exhibit a
      wider therapeutic window, in addition may reduce the need for adjuvant MAO-B
      inhibitor treatment. 

PMID- 24906470
TI  - Adherence to the DASH diet and prevalence of the metabolic syndrome among Iranian
      women.
AB  - PURPOSE: Epidemiologic data linking adherence to the dietary approaches to stop
      hypertension (DASH) diet and metabolic abnormalities is sparse and inconsistent.
      The association between habitual intake of the DASH diet and metabolic syndrome
      (MetS) has not been investigated in the Middle East. We aimed to determine
      whether usual adherence to the DASH dietary pattern was associated with MetS in a
      group of Iranian women. METHODS: This cross-sectional study was conducted in 2012
      among a representative sample of Isfahani female nurses. A validated, dish-based
      semiquantitative food frequency questionnaire was used for assessing usual
      dietary intakes. The DASH score was constructed based on 8 main foods and
      nutrients emphasized or minimized in the DASH diet. The MetS was defined
      according to the Joint Scientific Statement. RESULTS: After controlling for
      potential confounders, individuals in the highest tertile of the DASH diet score
      had 81% lower odds of MetS than those in the lowest category (OR 0.19; 95% CI
      0.07-0.96). Further, adjustment for body mass index slightly weakened the
      association (OR 0.37; 95% CI 0.14-0.91). Participants with the greater adherence
      to the DASH diet were 54, 73, 78, and 80% less likely to have enlarged waist
      circumference, hyperglyceridemia, low HDL-C levels, and high blood pressure,
      respectively, compared with those in the lowest tertile. No significant
      association was seen between consumption of a DASH diet and abnormal fasting
      plasma glucose. CONCLUSIONS: Adherence to the DASH eating plan was inversely
      associated with the odds of MetS and most of its features among a group of
      Iranian women.

PMID- 24906471
TI  - Folate administration decreases oxidative status and blood pressure in
      postmenopausal women.
AB  - PURPOSE: The purpose of this study was to evaluate whether folate exerts
      antioxidant effects in postmenopausal women and whether this effect is related to
      folate-induced modification of 24-h ambulatory blood pressure (BP). METHODS:
      Double-blind placebo-controlled study performed in 30 apparently healthy
      postmenopausal women recruited at the outpatient service of University Hospital.
      Women, free from hormones or substances possibly interfering with the
      investigated parameters, were randomized to receive orally for 3 weeks placebo (n
      = 15) or 15 mg/day of 5-methyltetrahydrofolate (5-MTHF; n = 15). Whole-blood free
      oxygen radicals test (FORT), free oxygen radical defence (FORD), lipids, glucose,
      insulin, insulin resistance [homeostatic model assessment for insulin resistance
      (HOMA-IR)], homocysteine and 24-h ambulatory BP values were evaluated. RESULTS:
      In the entire group of women, FORT was independently and inversely related to the
      day-night difference of diastolic (r = 0.420; p = 0.03) and mean BP (r = 0.497; p
      = 0.01). Placebo did not affect any biochemical or BP parameter. 5-MTHF reduced
      FORT (-71.5 +/- 98.2; p = 0.02) and increased FORD (0.5 +/- 0.9; p = 0.05),
      decreased insulin (p = 0.01), HOMA-IR (p = 0.0002) and homocysteine (p = 0.008).
      During 5-MTHF, night-time mean (p = 0.001) and diastolic BP (p = 0.002) decreased
      of about 5 mmHg and the day-night difference of mean (p = 0.001) and diastolic BP
      (p = 0.002) contemporaneously increased. FORT reduction was related to the
      amplification of the nocturnal decline of mean (0.697; p = 0.006) and diastolic
      BP (r = 0.777; p = 0.002) and to the amplification of the day-night difference of
      diastolic BP (r = 0.63; p = 0.015). CONCLUSIONS: Present data show a clear
      reduction of oxidative stress during 5-MTHF administration and a strong
      correlation between this decrease and the nocturnal decline of BP. The possible
      link between the two is worthy to be explored.

PMID- 24906473
TI  - Socioeconomic status and epithelial ovarian cancer survival in Sweden.
AB  - PURPOSE: To investigate socioeconomic disparities in epithelial ovarian cancer
      (EOC) survival in Sweden. METHODS: A cohort of 635 women with invasive EOC who
      participated in a nationwide population-based case-control study was included in
      the present population-based prospective study. Women were diagnosed with EOC
      between 1993 and 1995. Mortality until 31 December 2007 was determined through
      linkage with the Swedish Cause of Death Registry. Clinical data (tumor stage and
      tumor differentiation) and indicators of socioeconomic status (SES, education
      level, and annual individual disposable income) were retrieved from medical
      records and a nationwide database, respectively. The Cox proportional hazards
      regression model and the Laplace regression model were used to estimate the
      effect of clinical factors and SES on EOC survival. RESULTS: The main factors
      associated with EOC survival were tumor stage and tumor differentiation: women
      with stage II, III, and IV tumors had a greater mortality risk than those with
      stage I tumors [hazard ratio (HR) 2.65, 95 % confidence interval (CI) 1.73-4.07;
      HR 6.69, 95 % CI 4.85-9.22; HR 12.84, 95 % CI 8.90-18.66, respectively]. After
      adjustment for these tumor characteristics, no clear association remained between
      our indicators of SES and EOC survival, but better survival was observed among
      women with stage IV tumors and a higher income level, and among women with poorly
      differentiated tumors and a higher education level. Nevertheless, there was no
      evidence of extended survival among women with higher compared to lower SES.
      CONCLUSIONS: Our study provides no convincing evidence of an association between
      SES and EOC survival in Sweden.

PMID- 24906472
TI  - Independent positive association of plasma beta-carotene concentrations with
      adiponectin among non-diabetic obese subjects.
AB  - PURPOSE: Many epidemiological studies find an inverse correlation between
      carotenoids intake or carotenoids plasma concentrations and body mass index
      (BMI), insulin resistance or metabolic syndrome in the general population.
      However, it is not clear whether these relationships occur in obese population.
      METHODS: We conducted a cross-sectional study in 108 obese non-diabetic patients.
      RESULTS: There was an inverse correlation between plasma levels of pro-vitamin A
      carotenoids (alpha-carotene, beta-carotene and beta-cryptoxanthin) and both BMI
      and insulin resistance (estimated by the HOMA-IR). No correlation between plasma
      concentrations of lycopene or lutein/zeaxanthin and BMI or insulin resistance was
      found. The inverse association between the three pro-vitamin A carotenoids and
      HOMA-IR disappeared after adjustment for BMI and waist circumference.
      Interestingly, we identified a positive association between concentrations of
      beta-carotene and adiponectin in plasma that was independent of sex, age, smoking
      status, BMI and waist circumference. To our knowledge, such association has never
      been described in obese patients. CONCLUSION: These results suggest the existence
      of a favourable effect of beta-carotene on insulin sensitivity in obese
      individuals that could involve a positive regulation of adiponectin, either
      directly or via its pro-vitamin A activity. The demonstration of the potential
      benefits of beta-carotene towards insulin sensitivity would open the way to
      dietary strategies to prevent metabolic syndrome.

PMID- 24906474
TI  - Serum uric acid levels and cancer mortality risk among males in a large general
      population-based cohort study.
AB  - PURPOSE: Serum uric acid (SUA) has antioxidant capacities and therefore may
      protect against the development of cancer. Few epidemiological studies have
      tested this hypothesis, and findings were inconsistent. METHODS: We studied the
      association between SUA levels and mortality due to any type of cancer, and three
      common types of cancer among males (lung, colorectal, and prostate cancer) in the
      general population-based Vlagtwedde-Vlaardingen cohort with 38 years of follow-up
      and 8 surveys (total number of males = 4,350). Of 1,823 males with data available
      on SUA, 254 (13.9 %) died due to any cancer (lung n = 75 (4.1 %), colorectal n =
      27 (1.5 %), and prostate cancer n = 23 (1.3 %), assessed on 31 December 2008).
      SUA, cholesterol, and triglyceride were measured in males during the surveys in
      1970, 1972, and 1973. We analyzed the association between cancer mortality risk
      and SUA level both as continuous variable and as tertiles: lowest <5 mg/dl
      (reference), middle 5-5.8 mg/dl, and highest >5.8 mg/dl, using multivariate Cox
      regression with adjustment for age, smoking (pack years), and body mass index.
      RESULTS: Higher levels of SUA were associated with a lower risk of mortality from
      any cancer [HR (95 % CI) = 0.85 (0.73-0.97)]. SUA levels in the highest tertile
      (>5.8 mg/dl) were associated with a lower risk of mortality from any cancer [0.68
      (0.48-0.97)]. Additional adjustment for serum total cholesterol and triglyceride
      levels did not change the results. CONCLUSIONS: Our study indicates that elevated
      SUA levels may protect against cancer mortality.

PMID- 24906476
TI  - Preventive effects of jujube polysaccharides on fructose-induced insulin
      resistance and dyslipidemia in mice.
AB  - High fructose intake is associated with adverse metabolic syndromes. This study
      was designed to investigate whether the polysaccharides derived from Zizyphus
      jujube cv. Shaanbeitanzao (ZSP) could alleviate high fructose-induced insulin
      resistance and dyslipidemia in mice. ZSP was identified by capillary zone
      electrophoresis as an acidic heteropolysaccharide with l-arabinose, d-galactose
      and d-galacturonic acid being the main component monosaccharides. Mice were
      provided with 20% high-fructose water and ZSP was administered intragastrically
      at doses of 0, 200 or 400 mg kg(-1) BW for 4 weeks. Fructose-treated mice showed
      hyperglycemia, hyperinsulinemia and dyslipidemia with impaired insulin
      sensitivity (p < 0.05). Administration of ZSP at a dose of 400 mg kg(-1) BW
      significantly reduced the serum levels of glucose, insulin, TC, TG, LDL-C, and
      VLDL-C (p < 0.01). ZSP also markedly improved the HDL-C level, homeostasis model
      assessment for insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta),
      and decreased the atherogenic index (AI) of the mice exposed to high-fructose
      water. Histopathological test with H&E and oil red O staining confirmed liver
      steatosis induced by a high-fructose diet and the hepatoprotective effect of ZSP.
      These findings indicate that the jujube polysaccharides may ameliorate insulin
      resistance and dyslipidemia in fructose-treated mice. 

PMID- 24906475
TI  - Chemical characterization of milk oligosaccharides of the common brushtail possum
      (Trichosurus vulpecula).
AB  - Structural characterizations of marsupial milk oligosaccharides have been
      performed in only three species: the tammar wallaby, the red kangaroo and the
      koala. To clarify the homology and heterogeneity of milk oligosaccharides among
      marsupials, 21 oligosaccharides of the milk carbohydrate fraction of the common
      brushtail possum were characterized in this study. Neutral and acidic
      oligosaccharides were separated from the carbohydrate fraction of mid-lactation
      milk and characterized by (1)H-nuclear magnetic resonance spectroscopy and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry. The
      structures of the 7 neutral oligosaccharides were Gal(beta1-3)Gal(beta1-4)Glc (3'
      galactosyllactose), Gal(beta1-3)Gal(beta1-3)Gal(beta1-4)Glc (3", 3'
      digalactosyllactose), Gal(beta1-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-4)Glc,
      Gal(beta1-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-4)Glc, Gal(beta1
      3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (lacto-N-novopentaose I),
      Gal(beta1-3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (galactosyl
      lacto-N-novopentaose I), Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1
      3)Gal(beta1-4)Glc (galactosyl lacto-N-novopentaose II). The structures of the 14
      acidic oligosaccharides detected were Neu5Ac(alpha2-3)Gal(beta1-3)Gal(beta1-4)Glc
      (sialyl 3'-galactosyllactose), Gal(beta1-3)(O-3-sulfate)[Gal(beta1-4)GlcNAc(beta1
      6)]Gal(beta1-4)Glc (lacto-N-novopentaose I sulfate a) Gal(beta1-3)[Gal(beta1-4)(O
      3-sulfate)GlcNAc(beta1-6)]Gal(beta1-4)Glc (lacto-N-novopentaose I sulfate b),
      Neu5Ac(alpha2-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-4)Glc, Neu5Ac(alpha2
      3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (sialyl lacto-N
      novopentaose a), Gal(beta1-3)(-3-O-sulfate)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1
      6)]Gal(beta1-4)Glc, Gal(beta1-3)Gal(beta1-3)[Gal(beta1-4)(-3-O
      sulfate)GlcNAc(beta1-6)]Gal(beta1-4)Glc, Gal(beta1-3)[Neu5Ac(alpha2-6)Gal(beta1
      4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (sialyl lacto-N-novopentaose b), Neu5Ac(alpha2
      3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-4)Glc, Gal(beta1-3)(-3-O
      sulphate)Gal(beta1-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-4)Glc, Neu5Ac(alpha2
      3)Gal(beta1-3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc, Gal(beta1
      3)(-3-O-sulphate)Gal(beta1-3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1
      4)Glc, Gal(beta1-3)Gal(beta1-3)Gal(beta1-3)[Gal(beta1-4)(-3-O
      sulphate)GlcNAc(beta1-6)]Gal(beta1-4)Glc and Gal(beta1-3)Gal(beta1
      3)[Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (galactosyl sialyl
      lacto-N-novopentaose b). No fucosyl oligosaccharides were detected. Galactosyl
      lacto-N-novopentaose II, lacto-N-novopentaose I sulfate a, lacto-N-novopentaose I
      sulfate b and galactosyl sialyl lacto-N-novopentaose b are novel
      oligosaccharides. The results are compared with those of previous studies on
      marsupial milk oligosaccharides. 

PMID- 24906478
TI  - Model-based cost-effectiveness analyses for the treatment of chronic myeloid
      leukaemia: a review and summary of challenges.
AB  - Assessing the economic value of treatments for chronic myeloid leukaemia (CML) is
      important but poses a number of challenges. This paper reviews economic models of
      CML treatment to learn lessons from this experience and support ongoing efforts
      to model CML. A search of databases and submissions to key health technology
      assessment agencies identified 12 studies that reported 22 models. Common
      practice included the use of cohort Markov models-most models used health states
      organised around the key stages in CML: chronic phase, accelerated phase and
      blast phase-and the use of utility estimates in the literature that correspond
      with the National Institute for Health and Care Excellence reference case. Two
      key areas of uncertainty were the extrapolation of survival outcomes beyond the
      period observed by the trial; and the effectiveness of second-line therapies.
      Further work is required to overcome these uncertainties in existing models, such
      as longer-term trial data collection, including trials of second-line therapies;
      validation of health-related quality-of-life instruments; and the testing of
      alternative modelling approaches. In the meantime, it is important that the
      impact of uncertainties is tested through the use of sensitivity and scenario
      analysis. 

PMID- 24906477
TI  - Cost effectiveness of darunavir/ritonavir combination antiretroviral therapy for
      treatment-naive adults with HIV-1 infection in Canada.
AB  - OBJECTIVE: The AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects
      (ARTEMIS) clinical trial examined the efficacy and safety of two ritonavir
      boosted protease inhibitors (PI/r), darunavir/r 800/100 mg once daily (QD) and
      lopinavir/r 800/200 mg daily, both used in combination with tenofovir disoproxil
      fumarate/emtricitabine. This study aimed to assess the cost effectiveness of the
      darunavir/r regimen compared with the lopinavir/r regimen in treatment-naive
      adults with HIV-1 infection in Canada. METHODS: A Markov model with a 3-month
      cycle time and six CD4 cell-count-based health states (>500, 351-500, 201-500,
      101-200, 51-100, and 0-50 cells/mm(3)) followed a cohort of treatment-naive
      adults with HIV-1 infection through initial darunavir/r or lopinavir/r
      combination therapy and a common set of subsequent regimens over the course of
      their remaining lifetimes. Population characteristics and transition
      probabilities were estimated from the ARTEMIS clinical trial and other trials.
      Costs (in 2014 Canadian dollars), utilities, and mortality were estimated from
      Canadian sources and published literature. Costs and health outcomes were
      discounted at 5% per year. One-way and probabilistic sensitivity analyses were
      performed, including a simple indirect comparison of the darunavir/r initial
      regimen with an atazanavir/r-based regimen. RESULTS: In the base-case lifetime
      analysis, individuals receiving initial therapy with the darunavir/r regimen
      experienced 0.25 more quality-adjusted life-years (QALYs) with lower
      antiretroviral drug costs (-$14,246) and total costs (-$18,402) than individuals
      receiving the lopinavir/r regimen, indicating that darunavir/r dominated
      lopinavir/r. In an indirect comparison with an atazanavir/r-based regimen, the
      darunavir/r regimen remained the dominant choice, but with lower cost savings (
      $2,303) and QALY gains (0.02). Results were robust to a wide range of other
      changes in input parameter values, population characteristics, and modeling
      assumptions. The probabilistic sensitivity analysis demonstrated that the
      darunavir/r regimen was cost effective compared with the lopinavir/r regimen in
      over 86% of simulations for willingness-to-pay thresholds between $0 and $100,000
      per QALY gained. CONCLUSIONS: Darunavir/r 800/100 mg QD may be a cost-effective
      PI/r component of initial antiretroviral therapy for treatment-naive adults with
      HIV-1 infection in Canada.

PMID- 24906479
TI  - Ahead of its time? Reflecting on New Zealand's Pharmac following its 20th
      anniversary.
AB  - New Zealand's Pharmaceutical Management Agency (Pharmac) was created in 1993.
      Unusual in international terms, Pharmac's objective is to work within a fixed
      budget while ensuring the New Zealand public receives an adequate range of
      government-subsidised medicines. Following its 20th anniversary, this article
      reflects on Pharmac's development and role within the New Zealand health system,
      various changes over time to the agency's scope and activities, its performance
      and its present challenges. 

PMID- 24906480
TI  - Modelling the efficiency of codon-tRNA interactions based on codon usage bias.
AB  - The tRNA adaptation index (tAI) is a widely used measure of the efficiency by
      which a coding sequence is recognized by the intra-cellular tRNA pool. This index
      includes among others weights that represent wobble interactions between codons
      and tRNA molecules. Currently, these weights are based only on the gene
      expression in Saccharomyces cerevisiae. However, the efficiencies of the
      different codon-tRNA interactions are expected to vary among different organisms.
      In this study, we suggest a new approach for adjusting the tAI weights to any
      target model organism without the need for gene expression measurements. Our
      method is based on optimizing the correlation between the tAI and a measure of
      codon usage bias. Here, we show that in non-fungal the new tAI weights predict
      protein abundance significantly better than the traditional tAI weights. The
      unique tRNA-codon adaptation weights computed for 100 different organisms exhibit
      a significant correlation with evolutionary distance. The reported results
      demonstrate the usefulness of the new measure in future genomic studies. 

PMID- 24906482
TI  - The effects of low-intensity laser therapy on hepatic ischemia-reperfusion injury
      in a rat model.
AB  - Ischemia-reperfusion (I/R) is a major mechanism of liver injury following hepatic
      surgery or transplantation. Despite numerous reports on the role and relics of
      low-intensity laser therapy (LILT) in many organs, the potential effects of LILT
      on hepatic ischemia-reperfusion have not been explored. This study was aimed to
      investigate the impresses of LILT applied to the skin following hepatic ischemia
      and reperfusion. Thirty-six healthy male Wistar rats were allocated into three
      groups of twelve animals each as follows: Sham, Ischemia-reperfusion (IR), and
      Ischemia-reperfusion with laser treatment (IR+LILT). Hepatic ischemia was induced
      by clamping the arterial and portal venous for 45 min. A laser diode (400 mW, 804
      nm) was applied to the skin surface at the anatomical site of the liver at a dose
      of 3 J/cm(2), and the duration of irradiation was selected 120 s with 15-min
      interval after beginning the reperfusion. Animals were maintained under
      anesthesia and sacrificed 6 h subsequent reperfusion. Hepatic samples were
      evaluated for histological assessment and biochemistry analysis. Serum
      aminotransferase levels, tumor necrosis factor-alpha (TNF-alpha) levels,
      malondialdehyde (MDA), and glutathione (GSH) levels were significantly lower (P <
      0.05) in the irradiated group compared to the I/R group during the 6 h after
      reperfusion. The number of histopathological changes in the hepatic tissues was
      significantly lower in the treated group (P < 0.05). These observations suggest
      that LILT applied in transcutaneous manner effectively improves hepatic injuries
      after ischemia-reperfusion period in rats.

PMID- 24906481
TI  - The influence of low-level laser therapy on parameters of oxidative stress and
      DNA damage on muscle and plasma in rats with heart failure.
AB  - In heart failure (HF), there is an imbalance between the production of reactive
      oxygen species and the synthesis of antioxidant enzymes, causing damage to the
      cardiovascular function and increased susceptibility to DNA damage. The aim of
      this study was to evaluate the influence of low-level laser therapy (LLLT) on
      parameters of oxidative stress and DNA damage in skeletal muscle and plasma of
      rats with HF. Wistar rats were allocated into six groups: "placebo" HF rats (P
      HF, n = 9), "placebo" Sham rats (P-sham, n = 8), HF rats at a dose 3 J/cm(2) of
      LLLT (3 J/cm(2)-HF, n = 8), sham rats at a dose 3 J/cm(2) of LLLT (3 J/cm(2)
      sham, n = 8), HF rats at a dose 21 J/cm(2) of LLLT (21 J/cm(2)-HF, n = 8) and
      sham rats at a dose 21 J/cm(2) of LLLT (21 J/cm(2)-sham, n = 8). Animals were
      submitted to a LLLT protocol for 10 days at the right gastrocnemius muscle.
      Comparison between groups showed a significant reduction in superoxide dismutase
      (SOD) activity in the 3 J/cm(2)-HF group (p = 0.03) and the 21 J/cm(2)-HF group
      (p = 0.01) compared to the P-HF group. 2',7'-Dihydrodichlorofluorescein (DCFH)
      oxidation levels showed a decrease when comparing 3 J/cm(2)-sham to P-sham (p =
      0.02). The DNA damage index had a significant increase either in 21 J/cm(2)-HF or
      21 J/cm(2)-sham in comparison to P-HF (p = 0.004) and P-sham (p = 0.001) and to 3
      J/cm(2)-HF (p = 0.007) and 3 J/cm(2)-sham (p = 0.037), respectively. Based on
      this, laser therapy appears to reduce SOD activity and DCFH oxidation levels,
      changing the oxidative balance in the skeletal muscle of HF rats. Otherwise, high
      doses of LLLT seem to increase DNA damage.

PMID- 24906483
TI  - Measurement of pressure changes during laser-activated irrigant by an erbium,
      chromium: yttrium, scandium, gallium, garnet laser.
AB  - The use of Er,Cr:YSGG laser to activate irrigants results in the creation of
      vapour bubbles and shockwaves. The present study evaluated the magnitude of
      pressure changes in the root canal during laser-activated irrigation. The root
      canal of a single extracted maxillary canine was enlarged to a size 40/0.06 file.
      A pressure sensor was inserted apically into the root canal. The tooth was
      processed as follows. In the EDTA condition, the tooth was irrigated with 17 %
      EDTA; in the NaOCl condition, the tooth was irrigated with 3 % NaOCl. In all
      conditions, the irrigants were activated at 0.75 and 1.75 W for 60 s using RFT2
      and MZ2 tips; to analyse the effect of tip placement, the tip was activated at
      the orifice and after inserting the tip 5 mm deeper than the orifice. Data showed
      no significant difference between irrigation regimens (p > 0.05). There were no
      significant differences of the pressure between RFT2 and MZ2 tips (p > 0.05). The
      placement of tips closer to the apex resulted in significantly higher pressure
      than at the orifice (p < 0.001). The use of 1.75 W power resulted in a
      significantly higher increase of pressure compared to 0.75 W (p < 0.001),
      regardless either the type of solutions or tips used. The magnitude of the
      pressure changes in the root canal at 0.75 W was significantly lower than 1.75 W
      regardless of either type of tips or solutions used. The closer the insertion of
      the tip to the apex, the higher the pressure. 

PMID- 24906484
TI  - Diagnostic performance of a new red light LED device for approximal caries
      detection.
AB  - The aim of this study was to test a newly developed LED-based fluorescence device
      for approximal caries detection in vitro. We assembled 120 extracted molars
      without frank cavitations or fillings pairwise in order to create contact areas.
      The teeth were independently assessed by two examiners using visual caries
      detection (International Caries Detection and Assessment System, ICDAS), bitewing
      radiography (BW), laser fluorescence (LFpen), and LED fluorescence (Midwest
      Caries I.D., MW). The measurements were repeated at least 1 week later. The
      diagnostic performance was calculated with Bayesian analyses. Post-test
      probabilities were calculated in order to judge the diagnostic performance of
      combined methods. Reliability analyses were performed using kappa statistics for
      nominal data and intraclass correlation (ICC) for absolute data. Histology served
      as the gold standard. Sensitivities/specificities at the enamel threshold were
      0.33/0.84 for ICDAS, 0.23/0.86 for BW, 0.47/0.78 for LFpen, and 0.32/0.87 for MW.
      Sensitivities/specificities at the dentine threshold were 0.04/0.89 for ICDAS,
      0.27/0.94 for BW, 0.39/0.84 for LFpen, and 0.07/0.96 for MW. Reliability data
      were fair to moderate for MW and good for BW and LFpen. The combination of ICDAS
      and radiography yielded the best diagnostic performance (post-test probability of
      0.73 at the dentine threshold). The newly developed LED device is not able to be
      recommended for approximal caries detection. There might be too much signal loss
      during signal transduction from the occlusal aspect to the proximal lesion site
      and the reverse. 

PMID- 24906485
TI  - Identification of prognostic factors and surgical indications for metastatic
      gastric cancer.
AB  - BACKGROUND: The treatment of metastatic gastric cancer is not uniform, and the
      prognostic factors and indications for surgery are currently unclear. This
      retrospective study aimed to identify the prognostic factors and clinical
      indications for surgery in patients with metastatic gastric cancer. METHODS: A
      total of 123 consecutive patients with gastric cancer and synchronous distant
      metastasis treated between January 1999 and December 2011 were reviewed. Patient,
      tumor, laboratory, surgical, and chemotherapy factors were analyzed, with overall
      survival as the endpoint. Univariate analyses were performed using the log-rank
      test, multivariate analyses were performed using the Cox proportional hazards
      model, and Kaplan-Meier curves were used to estimate survival. Significance was
      set at p<0.05. RESULTS: The median overall survival time was 13.1 months. Ninety
      eight patients received chemotherapy. Twenty-eight patients underwent gastrectomy
      with metastasectomy and 55 underwent gastrectomy without metastasectomy. The
      median overall survival time for patients who underwent gastrectomy with
      metastasectomy, gastrectomy without metastasectomy, and no surgical intervention
      was 21.9 months, 12.5 months, and 7.2 months, respectively (p<0.001).
      Multivariate analysis identified gastrectomy with or without metastasectomy,
      performance status (PS) >= 3, neutrophil-to-lymphocyte ratio (NLR) >3.1, and
      carbohydrate antigen 19-9 (CA19-9) level >37 U/mL as predictors of poor survival.
      NLR and CA19-9 level were also independent prognostic factors in the group of
      patients who underwent surgery. CONCLUSIONS: High pretreatment NLR, CA19-9 level,
      and PS are predictors of poor prognosis in patients with metastatic gastric
      cancer. In selected patients, gastrectomy can be performed safely, and may be
      associated with longer survival.

PMID- 24906486
TI  - Cotreatment with interleukin 4 and interleukin 10 modulates immune cells and
      prevents hypertension in pregnant mice.
AB  - BACKGROUND: Excessive maternal immune system activation plays a central role in
      the development of the hypertensive disorder of pregnancy preeclampsia (PE). The
      immunomodulatory cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10) are
      dysregulated during PE; therefore we hypothesized that treatment with both
      recombinant IL-4 and IL-10 during pregnancy could prevent the development of PE
      in mice. METHODS: Using our mouse model of PE in which immune system activation
      is induced by the double-stranded RNA receptor agonist poly I:C, we gave daily
      injections of IL-4, IL-10, or both on days 13-17 of pregnancy. Mice were then
      killed on day 18. RESULTS: Poly I:C caused a significant increase in systolic
      blood pressure in pregnant (P-PIC) mice compared with vehicle-treated pregnant
      (P) mice. All 3 treatments significantly decreased blood pressure in P-PIC mice
      to P levels, ameliorated the endothelial dysfunction, and decreased placental
      TLR3 levels in P-PIC mice. However, only IL-4/IL-10 cotreatment prevented the
      proteinuria and increased incidence of fetal demise in P-PIC mice; IL-4 or IL-10
      alone had no effect. Additionally, only IL-4/IL-10 cotreatment prevented the
      significant increase in CD3(+)/gammadelta(+) T cells and CD11c(+) dendritic cells
      and significant decrease in CD11b(+)/CD14(-) suppressor monocytes, as well as
      completely prevented placental necrosis, in P-PIC mice. Importantly, IL-4/IL-10
      cotreatment in P mice had no detrimental effects. CONCLUSIONS: Taken together,
      these data demonstrate that exogenous IL-4 and IL-10 administration concurrently
      during pregnancy can normalize immune cell subsets and prevent PE induced by
      maternal immune system activation.

PMID- 24906487
TI  - Improved multiple displacement amplification (iMDA) and ultraclean reagents.
AB  - BACKGROUND: Next-generation sequencing sample preparation requires nanogram to
      microgram quantities of DNA; however, many relevant samples are comprised of only
      a few cells. Genomic analysis of these samples requires a whole genome
      amplification method that is unbiased and free of exogenous DNA contamination. To
      address these challenges we have developed protocols for the production of DNA
      free consumables including reagents and have improved upon multiple displacement
      amplification (iMDA). RESULTS: A specialized ethylene oxide treatment was
      developed that renders free DNA and DNA present within Gram positive bacterial
      cells undetectable by qPCR. To reduce DNA contamination in amplification
      reagents, a combination of ion exchange chromatography, filtration, and lot
      testing protocols were developed. Our multiple displacement amplification
      protocol employs a second strand-displacing DNA polymerase, improved buffers,
      improved reaction conditions and DNA free reagents. The iMDA protocol, when used
      in combination with DNA-free laboratory consumables and reagents, significantly
      improved efficiency and accuracy of amplification and sequencing of specimens
      with moderate to low levels of DNA. The sensitivity and specificity of sequencing
      of amplified DNA prepared using iMDA was compared to that of DNA obtained with
      two commercial whole genome amplification kits using 10 fg (~1-2 bacterial cells
      worth) of bacterial genomic DNA as a template. Analysis showed >99% of the iMDA
      reads mapped to the template organism whereas only 0.02% of the reads from the
      commercial kits mapped to the template. To assess the ability of iMDA to achieve
      balanced genomic coverage, a non-stochastic amount of bacterial genomic DNA (1
      pg) was amplified and sequenced, and data obtained were compared to sequencing
      data obtained directly from genomic DNA. The iMDA DNA and genomic DNA sequencing
      had comparable coverage 99.98% of the reference genome at >=1X coverage and 99.9%
      at >=5X coverage while maintaining both balance and representation of the genome.
      CONCLUSIONS: The iMDA protocol in combination with DNA-free laboratory
      consumables, significantly improved the ability to sequence specimens with low
      levels of DNA. iMDA has broad utility in metagenomics, diagnostics, ancient DNA
      analysis, pre-implantation embryo screening, single-cell genomics, whole genome
      sequencing of unculturable organisms, and forensic applications for both human
      and microbial targets.

PMID- 24906490
TI  - The exposome: a new paradigm to study the impact of environment on health.
AB  - Environmental factors, here taken to include pollutants, lifestyle factors and
      behaviours, can play an important role in serious, chronic pathologies with large
      societal and economic costs, including respiratory disease. However, measurement
      of the environmental component in epidemiological studies has traditionally
      relied on much more uncertain and incomplete assessments than measurement of the
      genome. The 'exposome' has therefore been proposed as a new paradigm to encompass
      the totality of human environmental (meaning all non-genetic) exposures from
      conception onwards, complementing the genome. Evidently, there are large
      challenges in developing the exposome concept into a workable approach for
      epidemiological research. These include: (1) the accurate and reliable
      measurement of many exposures in the external environment, (2) the measurement of
      a wide range of biological responses in the internal environment, and (3)
      addressing the dynamic, life course nature of the exposome. New tools and
      technologies that can be applied to address these challenges include exposure
      biomarker technologies, geographical mapping and remote sensing technologies,
      smartphone applications and personal exposure sensors, and high-throughput
      molecular 'omics' techniques. Prospective, population-based cohort studies have
      recently started to implement these methods using the exposome framework. The
      exposome thus offers a new and exciting paradigm for improvement and integration
      of currently scattered and uncertain data on the environmental component in
      disease aetiology. This should lead to a better understanding of the role of
      environmental risk factors in respiratory disease and other chronic pathologies,
      and ultimately to better primary prevention strategies. 

PMID- 24906489
TI  - Prevalence of impacted and transmigrated canine teeth in a Cypriote orthodontic
      population in the Northern Cyprus area.
AB  - BACKGROUND: The aim of this study was two-fold; (1) to evaluate the prevalence
      and patterns of impacted canines and transmigrated canine teeth, and (2) to
      evaluate the possible relationships between impacted teeth, malocclusions and
      systemic conditions in an orthodontic patient population. METHODS: The clinical
      records and panoramic radiographs of 453 patients [201 (44.3%) male and 252
      (55.7%) female] referred to our outpatient clinic between January 2008 and
      January 2012 were retrospectively evaluated. The number, position, localization
      (right/left) and transmigration of teeth, as well as sex, age and systemic
      conditions of patients, were noted. An impacted canine was considered to be
      transmigrated when at least part of its length had crossed the midline.
      Complications related to impacted teeth (pain, cystic changes, root resorption or
      eruption disturbance of adjacent teeth) were also noted. A p-value less than 0.05
      was considered statistically significant. RESULTS: Impacted and transmigrated
      canine teeth were found in 16 (3.53%) and two (0.44%) patients in the study
      group, respectively. Root resorption was seen in four teeth adjacent to impacted
      canines. No statistical difference was found among gender, location, malocclusion
      and impaction of the teeth (p > 0.05). However, maxillary canine impaction
      occurred significantly more frequently than mandibular canine impaction (p <
      0.05). CONCLUSIONS: The early detection of impacted as well as transmigrated
      teeth is crucial for successful treatment, therefore demographic studies are
      important. Although larger samples are required, this study provides a baseline
      regarding the frequency and type of impacted canines in this particular
      population.

PMID- 24906488
TI  - Periodic Estrogen Receptor-Beta Activation: A Novel Approach to Prevent Ischemic
      Brain Damage.
AB  - In women, the risk for cerebral ischemia climbs rapidly after menopause. At
      menopause, production of ovarian hormones; i.e., progesterone and estrogen,
      slowly diminishes. Estrogen has been suggested to confer natural protection to
      premenopausal women from ischemic stroke and some of its debilitating
      consequences. This notion is also strongly supported by laboratory studies
      showing that a continuous chronic 17beta-estradiol (E2; a potent estrogen)
      regimen protects brain from ischemic injury. However, concerns regarding the
      safety of the continuous intake of E2 were raised by the failed translation to
      the clinic. Recent studies demonstrated that repetitive periodic E2
      pretreatments, in contrast to continuous E2 treatment, provided neuroprotection
      against cerebral ischemia in ovariectomized rats. Periodic E2 pretreatment
      protects hippocampal neurons through activation of estrogen receptor subtype beta
      (ER-beta). Apart from neuroprotection, periodic activation of ER-beta in
      ovariectomized rats significantly improves hippocampus-dependent learning and
      memory. Difficulties in learning and memory loss are the major consequence of
      ischemic brain damage. Periodic ER-beta agonist pretreatment may provide
      pharmacological access to a protective state against ischemic stroke and its
      debilitating consequences. The use of ER-beta-selective agonists constitutes a
      safer target for future research than ER-alpha agonist or E2, inasmuch as it
      lacks the ability to stimulate the proliferation of breast or endometrial tissue.
      In this review, we highlight ER-beta signaling as a guide for future
      translational research to reduce cognitive decline and cerebral ischemia
      incidents/impact in post-menopausal women, while avoiding the side effects
      produced by chronic E2 treatment. 

PMID- 24906491
TI  - Impact of empiric nesiritide or milrinone infusion on early postoperative
      recovery after Fontan surgery: a randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: We sought to determine whether empirical nesiritide or milrinone
      would improve the early postoperative course after Fontan surgery. We
      hypothesized that compared with milrinone or placebo, patients assigned to
      receive nesiritide would have improved early postoperative outcomes. METHODS AND
      RESULTS: In a single-center, randomized, double-blinded, placebo-controlled,
      multi-arm parallel-group clinical trial, patients undergoing primary Fontan
      surgery were assigned to receive nesiritide, milrinone, or placebo. A loading
      dose of study drug was administered on cardiopulmonary bypass followed by a
      continuous infusion for >=12 hours and <=5 days after cardiac intensive care unit
      admission. The primary outcome was days alive and out of the hospital within 30
      days of surgery. Secondary outcomes included measures of cardiovascular function,
      renal function, resource use, and adverse events. Among 106 enrolled subjects,
      35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups,
      respectively, and all were analyzed based on intention to treat. Demographics,
      patient characteristics, and operative factors were similar among treatment
      groups. No significant treatment group differences were found for median days
      alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum
      to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment
      groups did not significantly differ in cardiac index, arrhythmias, peak lactate,
      inotropic scores, urine output, duration of mechanical ventilation, intensive
      care or chest tube drainage, or adverse events. CONCLUSIONS: Compared with
      placebo, empirical perioperative nesiritide or milrinone infusions are not
      associated with improved early clinical outcomes after Fontan surgery. CLINICAL
      TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00543309.

PMID- 24906492
TI  - The effectiveness of recruitment strategies on general practitioner's survey
      response rates - a systematic review.
AB  - BACKGROUND: Low survey response rates in general practice are common and lead to
      loss of power, selection bias, unexpected budgetary constraints and time delays
      in research projects. METHODS:  OBJECTIVE: To assess the effectiveness of
      recruitment strategies aimed at increasing survey response rates among GPs.
      DESIGN: Systematic review. SEARCH METHODS: MEDLINE (OVIDSP, 1948-2012), EMBASE
      (OVIDSP, 1980-2012), Evidence Based Medicine Reviews (OVIDSP, 2012) and
      references of included papers were searched. Major search terms included GPs,
      recruitment strategies, response rates, and randomised controlled trials (RCT).
      SELECTION CRITERIA: Cluster RCTs, RCTs and factorial trial designs that evaluate
      recruitment strategies aimed at increasing GP survey response rates. DATA
      COLLECTION AND ANALYSIS: Abstracts identified by the search strategy were
      reviewed and relevant articles were retrieved. Each full-text publication was
      examined to determine whether it met the predetermined inclusion criteria. Data
      extraction and study quality was assessed by using predetermined checklists.
      RESULTS: Monetary and nonmonetary incentives were more effective than no
      incentive with monetary incentives having a slightly bigger effect than
      nonmonetary incentives. Large incentives were more effective than small
      incentives, as were upfront monetary incentives compared to promised monetary
      incentives. Postal surveys were more effective than telephone or email surveys.
      One study demonstrated that sequentially mixed mode (online survey followed by a
      paper survey with a reminder) was more effective than an online survey or the
      combination of an online and paper survey sent similtaneously in the first mail
      out. Pre-contact with a phonecall from a peer, personalised packages, sending
      mail on Friday, and using registered mail also increased response rates in single
      studies. Pre-contact by letter or postcard almost reached statistical
      signficance. CONCLUSIONS: GP survey response rates may improve by using the
      following strategies: monetary and nonmonetary incentives, larger incentives,
      upfront monetary incentives, postal surveys, pre-contact with a phonecall from a
      peer, personalised packages, sending mail on Friday, and using registered mail.
      Mail pre-contact may also improve response rates and have low costs. Improved
      reporting and further trials, including sequential mixed mode trials and social
      media, are required to determine the effectiveness of recruitment strategies on
      GPs' response rates to surveys.

PMID- 24906493
TI  - Radiographic features of pulmonary embolism: Westermark and Palla signs.

PMID- 24906494
TI  - Cytomegalovirus and glioma: putting the cart before the horse.
AB  - In 1908, Oluf Bang and Vilhelm Ellerman laid the foundation for theory of
      oncoviruses by demonstrating that the avian erythroblastosis (a form of chicken
      leukaemia) could be transmitted by cell-free extracts. Since then, it has been
      shown very convincingly that viruses can directly cause several human cancers by
      various mechanisms. Epidemiological data imply that viruses are the second most
      important risk factor for cancer development in humans, exceeded only by tobacco
      consumption. Although the ability of certain viruses (hepatitis B and C, human
      papillomavirus, etc) to cause cancer has been time tested and proven
      scientifically, there are several other potential viral candidates whose role in
      oncogenesis is more controversial. One such controversial scenario involves the
      role of cytomegalovirus (CMV) in malignant gliomas, the most common form of
      primary brain tumour. CMV first attracted attention about a decade ago when CMV
      gene products were found in glioma tissue but not in normal brain. Since this
      initial observation, several different groups have shown an oncomodulatory effect
      of CMV; however, direct association between CMV infection and incidence of glioma
      is lacking. In this review, we will evaluate the evidence, both preclinical and
      clinical, regarding the possible role of CMV in gliomagenesis and maintenance. We
      will also critically evaluate the rationale for using antiviral drugs in the
      treatment of patients with glioma. 

PMID- 24906495
TI  - A comparison of midwife-led care versus obstetrician-led care for low-risk women
      in Japan.
AB  - BACKGROUND: Continuity of midwife-led care is recommended in maternity care
      because of its various positive outcomes. In Japan, midwife-led care is receiving
      broad attention as well. In order to popularise midwifery care within the entire
      system of perinatal care in Japan, there is a need to show evidence that
      continuity of midwife care for women will bring about positive outcomes. AIM: The
      objectives of this study were to compare the health outcomes of women and infants
      who received midwife-led care with obstetrician-led care in Japan. METHODS: This
      was an observational study using non-random purposive sampling with a survey
      questionnaire. Settings where midwife-led care and obstetrician-led care were
      chosen by purposive samples. Participants were low-risk women who received
      antenatal care and delivered a term-singleton-infant at the participating
      settings during the research period. Measurements were: Women-centred care
      pregnancy questionnaire, Stein's maternity blues questionnaire, and Edinburgh
      Postnatal Depression Scale. FINDINGS: Midwife-led care was perceived by women to
      be beneficial and had no adverse outcomes compared to obstetrician-led care. Main
      findings are: (1) Perception of Women-centred care was higher; (2) Less premature
      rupture of membranes, and the Apgar scores of the infants were similar; (3)
      Exclusively breast-feeding during hospitalisation and at one-month postpartum;
      (4) Stein's maternity blues scale scores was lower in women who received midwife
      led care than those who received obstetrician-led care. CONCLUSIONS: Continuity
      of midwife-led care was perceived by women to be beneficial and had no adverse
      outcomes. Therefore, midwife-led care in low-risk pregnancy could be applicable
      and recommended.

PMID- 24906496
TI  - Tissue Viability Society contributing to international debate.

PMID- 24906498
TI  - Neurorobotics: a Holy Grail to practice reality continuum.

PMID- 24906499
TI  - Integration of pharmacokinetic and pharmacodynamic indices of valnemulin in
      broiler chickens after a single intravenous and intramuscular administration.
AB  - The antibacterial efficacy of valnemulin against Staphylococcus aureus was
      studied ex vivo in broiler chickens after intravenous and intramuscular
      administration at a dose of 10 mg/kg bodyweight (BW). The minimum inhibitory
      concentrations (MICs) of valnemulin against S. aureus strains ATCC 25923 in broth
      and serum were 0.12 and 1 ug/mL, respectively. The MIC50 and MIC90 of valnemulin
      against all susceptible S. aureus strains isolated from chickens in the test
      population were 0.06 and 0.12 MUg/mL, respectively. Protein binding, which
      greatly influences the efficacy of valnemulin, was assayed by equilibrium
      dialysate in vitro. A high binding fraction of 86.2% was found, which seems in
      good agreement with the difference of bacterial susceptibility tests observed in
      broth and serum. The surrogate index of AUC0-24/MIC required for the lowest
      bacteriostatic effect, and 2 log10CFU reduction in bacterial count were 24.4 h
      and 38.0 h, respectively. The required daily dose of valnemulin for a
      bacteriostatic activity was calculated to be 15 mg/kg BW based on the MIC90 of
      0.12 ug/mL. Considering the slow disposition process of valnemulin and an AUC0-24
      h value of more than 10-fold obtained from diseased animals, a suggested dose of
      3 mg/kg BW is sufficient to achieve a satisfactory therapeutic efficacy in
      infected broilers. Due to the time-dependent antibacterial characteristics of
      valnemulin, the recommended daily dose should be split into two or three sub
      doses to achieve the highest effectiveness while diminishing the risk of
      development of bacterial resistance.

PMID- 24906497
TI  - Sensitisation of TRPV4 by PAR2 is independent of intracellular calcium signalling
      and can be mediated by the biased agonist neutrophil elastase.
AB  - Proteolytic activation of protease-activated receptor 2 (PAR2) may represent a
      major mechanism of regulating the transient receptor potential vanilloid 4
      (TRPV4) non-selective cation channel in pathophysiological conditions associated
      with protease activation (e.g. during inflammation). To provide
      electrophysiological evidence for PAR2-mediated TRPV4 regulation, we
      characterised the properties of human TRPV4 heterologously expressed in Xenopus
      laevis oocytes in the presence and absence of co-expressed human PAR2. In outside
      out patches from TRPV4 expressing oocytes, we detected single-channel activity
      typical for TRPV4 with a single-channel conductance of about 100 pS for outward
      and 55 pS for inward currents. The synthetic TRPV4 activator GSK1016790A
      stimulated TRPV4 mainly by converting previously silent channels into active
      channels with an open probability of nearly one. In oocytes co-expressing TRPV4
      and PAR2, PAR2 activation by trypsin or by specific PAR2 agonist SLIGRL-NH2
      potentiated the GSK1016790A-stimulated TRPV4 whole-cell currents several fold,
      indicative of channel sensitisation. Pre-incubation of oocytes with the calcium
      chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM did
      not reduce the stimulatory effect of PAR2 activation on TRPV4, which indicates
      that the effect is independent of intracellular calcium signalling. Neutrophil
      elastase, a biased agonist of PAR2 that does not induce intracellular calcium
      signalling, also caused a PAR2-dependent sensitisation of TRPV4. The Rho-kinase
      inhibitor Y27362 abolished elastase-stimulated sensitisation of TRPV4, which
      indicates that Rho-kinase signalling plays a critical role in PAR2-mediated TRPV4
      sensitisation by the biased agonist neutrophil elastase. During acute
      inflammation, neutrophil elastase may sensitise TRPV4 by a mechanism involving
      biased agonism of PAR2 and activation of Rho-kinase.

PMID- 24906500
TI  - A high-grain diet alters the omasal epithelial structure and expression of tight
      junction proteins in a goat model.
AB  - The omasal epithelial barrier plays important roles in maintaining nutrient
      absorption and immune homeostasis in ruminants. However, little information is
      currently available about the changes in omasal epithelial barrier function at
      the structural and molecular levels during feeding of a high-grain (HG) diet. Ten
      male goats were randomly assigned to two groups, fed either a hay diet (0% grain;
      n = 5) or HG diet (65% grain; n = 5). Changes in omasal epithelial structure and
      expression of tight junction (TJ) proteins were determined via electron
      microscopy and Western blot analysis. After 7 weeks on each diet, omasal contents
      in the HG group showed significantly lower pH (P <0.001) and significantly higher
      concentrations of free lipopolysaccharides (LPS; P = 0.001) than the hay group.
      The goats fed a HG diet showed profound alterations in omasal epithelial
      structure and TJ proteins, corresponding to depression of thickness of total
      epithelia, stratum granulosum, and the sum of the stratum spinosum and stratum
      basale, marked epithelial cellular damage, erosion of intercellular junctions and
      down-regulation in expression of the TJ proteins, claudin-4 and occludin. The
      study demonstrates that feeding a HG diet is associated with omasal epithelial
      cellular damage and changes in expression of TJ proteins. These research findings
      provide an insight into the possible significance of diet on the omasal
      epithelial barrier in ruminants.

PMID- 24906501
TI  - Long term effects of Escherichia coli mastitis.
AB  - Escherichia coli is one of the most frequently diagnosed causes of bovine
      mastitis, and is typically associated with acute, clinical mastitis. The
      objective of the present study was to evaluate the long term effects of
      intramammary infections by E. coli on milk yield and quality, especially milk
      coagulation. Twenty-four Israeli Holstein cows diagnosed with clinical mastitis
      due to intramammary infection by E. coli were used in this study. Mean lactation
      number, days in milk (DIM) and daily milk yield (DMY) at the time of infection
      was 3.3 +/- 1.3, 131.7 days +/- 78.6 and 45.7 L +/- 8.4, respectively. DMY, milk
      constituents, somatic cells count (SCC), differential leukocytes count and
      coagulation parameters were subsequently assessed. Two patterns of inflammation
      were identified: 'short inflammation', characterized by <15% decrease in DMY and
      <30 days until return to normal (n = 5), and 'long inflammation', characterized
      by >15% decrease in DMY and >30 days to reach a new maximum DMY (n = 19). The
      estimated mean loss of marketable milk during the study was 200 L/cow for 'short
      inflammation' cases, and 1,500 L/cow for 'long inflammation' ones. Significant
      differences between 'short' and 'long inflammation' effects were found in almost
      all parameters studied. Long-term detrimental effects on milk quality were found
      regardless of clinical or bacteriological cure of affected glands.

PMID- 24906502
TI  - Collaborative development of clinical trials education programs for African
      American community-based organizations.
AB  - This paper describes the use of a unique "Learning and Feedback? approach to
      customize cancer clinical trials education programs for Community Bridges, a peer
      training intervention designed for African-American communities in North
      Carolina. Generic community education modules were demonstrated with key
      community leaders who were designated as trainers. Quantitative and qualitative
      assessments were provided on understanding of content, comfort with material, and
      cultural relevance. The generic materials were adapted into three revised
      modules, all featuring key messages about cancer clinical trials, discussion
      regarding distrust of medical research, common misconceptions about trials,
      patient protections, and a call to action to prompt increased inquiry about
      locally available trials. The revised modules were then used as part of a train
      the-trainer program with 12 African-American community leaders. ENACCT's use of
      the Learning and Feedback process is an innovative method for culturally adapting
      clinical trials education. 

PMID- 24906503
TI  - Celebrating 10 Years of Undergraduate Medical Education: A Student-Centered
      Evaluation of the Princess Margaret Cancer Centre--Determinants of Community
      Health Year 2 Program.
AB  - Between 2000 and 2011, over 170 second-year medical students participated in a
      Determinants of Community Health (DOCH 2) project at Princess Margaret Hospital
      (PMH). Students undertook community-based research projects at the hospital or
      with PMH community partners involving activities such as producing a literature
      review, writing a research proposal, obtaining ethics approval, carrying out data
      collection and analysis, presenting their data to classmates and supervisors, and
      production of a final report. An electronic survey consisting of both
      quantitative and qualitative questions was developed to evaluate the PMH-DOCH 2
      program and was distributed to 144 past students with known email addresses.
      Fifty-eight students responded, a response rate of 40.3%. Data analysis indicates
      that an increase in oncology knowledge, awareness of the impact of determinants
      of health on patients, and knowledge of research procedures increased
      participants' satisfaction and ability to conduct research following DOCH 2.
      Furthermore, the PMH-DOCH 2 program enhanced the development of CanMEDS
      competencies through career exploration and patient interaction as well as
      through shadowing physicians and other allied health professionals. In addition,
      some students felt their PMH-DOCH 2 projects played a beneficial role during
      their residency matching process. The PMH-DOCH 2 research program appeared to
      provide a positive experience for most participants and opportunities for medical
      students' professional growth and development outside the confines of traditional
      lecture-based courses.

PMID- 24906504
TI  - Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and
      their clinical subtypes.
AB  - Lung cancer is one of the most common human cancers worldwide. Among all lung
      cancer cases, non-small cell lung cancer (NSCLC) accounts for approximately 85%.
      Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts that have been
      shown to play important roles in tumourigenesis and tumor progression. To reveal
      novel tumor-related lncRNAs in NSCLC and their associations with clinical
      subtypes, we herein identified 2935 probe sets mapped to lncRNAs on Affymetrix HG
      U133 Plus 2.0 array with an lncRNA classification pipeline. We found 47 lncRNAs
      differentially expressed between normal lung tissues and tumor samples and 19
      lncRNAs differed in expression between SCC and AC, two subtypes of NSCLC, after
      analyses of the gene expression profiles of five datasets downloaded from the
      gene expression omnibus (GEO) with a leave one dataset out validation process.
      The different lncRNA expression profiles between NSCLC and normal tissue and
      between the subtypes of NSCLC may have potential implications in the pathogenesis
      of this cancer. lncRNAs screening may be beneficial in the diagnosis,
      subclassification, and the personalized treatment of NSCLC. 

PMID- 24906505
TI  - In vitro activities of oritavancin and comparators against meticillin-resistant
      Staphylococcus aureus (MRSA) isolates harbouring the novel mecC gene.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) is routinely detected by
      amplification of the mecA gene. Recently, MRSA isolates harbouring a novel mec
      gene (mecC) that is not detected by mecA amplification have been reported. In
      this study, the activities of the lipoglycopeptide oritavancin as well as the
      comparators vancomycin, daptomycin and linezolid against 14 mecC MRSA isolates
      were studied by broth microdilution minimum inhibitory concentration (MIC) and
      time-kill assays at clinically relevant concentrations of each antibacterial
      agent. Oritavancin, vancomycin, daptomycin and linezolid MIC90 values (MIC
      required to inhibit 90% of the isolates) against the mecC isolates were 0.06, 1,
      1 and 2mg/L, respectively. In time-kill assays, oritavancin at concentrations
      reflective of its free peak in plasma of patients receiving a single 1200 mg
      intravenous dose and the level 24h thereafter was bactericidal against all
      isolates tested, attaining 3 log kill relative to the starting inoculum between 5
      min and 15 min. Vancomycin both at its free peak and free trough concentrations
      was also bactericidal against all isolates, attaining bactericidal activity
      between 6h and 24h. Daptomycin was bactericidal only at its free peak
      concentration, attaining bactericidal activity between 30 min and 4h against the
      tested isolates. Linezolid was bacteriostatic (<3 log kill relative to the
      starting inoculum) against the tested isolates. Oritavancin's in vitro activity
      against mecC MRSA isolates was indistinguishable from that against mecA MRSA
      isolates both in MIC and time-kill assays.

PMID- 24906506
TI  - Epidermoid cyst of the coronal sulcus mimicking penile cancer: a case report.
AB  - INTRODUCTION: Epidermoid cysts represent common benign tumors occurring anywhere
      in the body but very rarely in the penis. Only a few cases of penile localization
      have been reported in the literature so far, most of them being congenital and/or
      idiopathic, usually presenting in children as slow-growing, solitary, well
      delimited cystic lesions. Here, we describe the case of a patient with a penile
      epidermoid cyst presenting as an ulcerated lesion of the coronal sulcus, thus
      mimicking penile cancer. CASE PRESENTATION: A 36-year-old Caucasian man presented
      with a three-month history of a rapidly growing asymptomatic ulcerated lesion in
      the ventral portion of the penile coronal sulcus. At surgical exploration, the
      area under the ulcerated lesion had a well-demarcated cystic shape; following its
      wide excision, an intraoperative histological examination revealed an epidermoid
      cyst. No recurrence had occurred at nine years of follow-up. CONCLUSIONS: Rare
      benign tumors of the penis, like the described epidermoid cyst, may mimic cancer.
      Nevertheless, penile ulcerated lesions should always be surgically explored as
      wide excision and intraoperative histological examination remain the only means
      of obtaining a precise disease definition and, consequently, administering the
      appropriate treatment.

PMID- 24906507
TI  - Primary prevention ICDs: why replace them if they haven't been used?

PMID- 24906508
TI  - Short-term effects of air temperature on cause-specific cardiovascular mortality
      in Bavaria, Germany.
AB  - OBJECTIVE: This time series study aimed to examine the association between daily
      air temperature and cause-specific cardiovascular mortality in Bavaria, Southern
      Germany. METHODS: We obtained data from the cities Munich, Nuremberg and Augsburg
      and two adjacent administrative districts (Augsburg and Aichach-Friedberg), for
      the period 1990-2006. Data included daily cause-specific cardiovascular death
      counts, mean daily meteorological variables and air pollution concentrations. In
      the first stage, data were analysed for Munich, Nuremberg and the Augsburg region
      separately using Poisson regression models combined with distributed lag non
      linear models adjusting for long-term trend, calendar effects and meteorological
      factors. In a second stage, we combined city-specific exposure-response
      relationships through a multivariate meta-analysis framework. RESULTS: An
      increase in the 2-day average temperature from the 90th (20.0 degrees C) to the
      99th centiles (24.8 degrees C) resulted in an increase of cardiovascular
      mortality by 10% (95% CI 5% to 15%) in the pooled analysis, while for a decrease
      from the 10th (-1.0 degrees C) to the 1st centiles (-7.5 degrees C) in the 15-day
      average temperature cardiovascular mortality increased by 8% (95% CI 2% to 14%).
      Strongest consistent risk estimates were seen for high 2-day average temperatures
      and mortality due to other heart diseases (including arrhythmias and heart
      failure) and cerebrovascular diseases, especially in the elderly. CONCLUSIONS:
      Results indicate that, in addition to low temperatures, high temperatures
      increase cause-specific cardiovascular mortality in temperature climates. These
      findings may guide planning public health interventions to control and prevent
      the health effects of exposure to air temperature, especially for individuals at
      risk for mortality due to heart failure, arrhythmias or cerebrovascular diseases.

PMID- 24906509
TI  - Functional magnetic resonance imaging of intrinsic brain networks for
      translational drug discovery.
AB  - Developing translational biomarkers is a priority for psychiatry research. Task
      independent functional brain imaging is a relatively novel technique that allows
      examination of the brain's intrinsic networks, defined as functionally and
      (often) structurally connected populations of neurons whose properties reflect
      fundamental neurobiological organizational principles of the central nervous
      system. The ability to study the activity and organization of these networks has
      opened a promising new avenue for translational investigation, because they can
      be analogously examined across species and disease states. Interestingly, imaging
      studies have revealed shared spatial and functional characteristics of the
      intrinsic network architecture of the brain across species, including mice, rats,
      non-human primates, and humans. Using schizophrenia as an example, we show how
      intrinsic networks may show similar abnormalities in human diseases and animal
      models of these diseases, supporting their use as biomarkers in drug development.

PMID- 24906510
TI  - Design, synthesis, antiviral and cytostatic activity of omega-(1H-1,2,3-triazol-1
      yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues.
AB  - The efficient synthesis of a new series of polyhydroxylated dibenzyl omega-(1H
      1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described
      starting from dibenzyl omega-azido(polyhydroxy)alkylphosphonates and selected
      alkynes under microwave irradiation. Selected O,O-dibenzylphosphonate
      acyclonucleotides were transformed into the respective phosphonic acids. All
      compounds were evaluated in vitro for activity against a broad variety of DNA and
      RNA viruses and for cytostatic activity against murine leukemia L1210, human T
      lymphocyte CEM and human cervix carcinoma HeLa cells. Compound (1S,2S)-16b
      exhibited antiviral activity against Influenza A H3N2 subtype (EC50=20MUM-visual
      CPE score; EC50=18MUM-MTS method; MCC >100MUM, CC50 >100MUM) in Madin Darby
      canine kidney cell cultures (MDCK), and (1S,2S)-16k was active against vesicular
      stomatitis virus and respiratory syncytial virus in HeLa cells (EC50=9 and 12MUM,
      respectively). Moreover, compound (1R,2S)-16l showed activity against both herpes
      simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC50=2.9 and 4MUM,
      respectively) and feline herpes virus in CRFK cells (EC50=4MUM) but at the same
      time it exhibited cytotoxicity toward uninfected cell (MCC?4MUM). Several other
      compounds have been found to inhibit proliferation of L1210, CEM as well as HeLa
      cells with IC50 in the 4-50MUM range. Among them compounds (1S,2S)- and (1R,2S)
      16l were the most active (IC50 in the 4-7MUM range). 

PMID- 24906511
TI  - Structure-activity relationship study of non-steroidal NPC1L1 ligands identified
      through cell-based assay using pharmacological chaperone effect as a readout.
AB  - Niemann-Pick type C1-like 1 (NPC1L1) is an intestinal cholesterol transporter
      that is known to be the target of the cholesterol absorption inhibitor ezetimibe.
      We previously discovered steroidal NPC1L1 ligands by using a novel cell-based
      assay that employs pharmacological chaperone effect as a readout. Those steroid
      derivatives bound to a site different from both the sterol-binding domain and the
      ezetimibe-binding site, implying that they may be a novel class of NPC1L1
      inhibitors with a distinct mode of action. As an extension of that work, we aimed
      here to find non-steroidal NPC1L1 ligands, which may be better candidates for
      clinical application than steroidal ligands, by using the same assay to screen
      our focused library of ligands for liver X receptor (LXR), a nuclear receptor
      that recognizes oxysterols as endogenous ligands. Here we describe identification
      of a novel class of NPC1L1 ligands with a ring-fused quinolinone scaffold, and an
      analysis of the structure-activity relationships of their derivatives as NPC1L1
      ligands. 

PMID- 24906512
TI  - Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine
      resistant strain.
AB  - Emergence and spread of multidrug resistant strains of Plasmodium falciparum has
      severely limited the antimalarial chemotherapeutic options. In order to overcome
      the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized
      and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1)
      strains of P. falciparum. The key feature of the designed molecules is the use of
      methylpiperazine linked alpha, beta(3)- and gamma-amino acids to generate novel
      side chain modified 4-aminoquinoline analogues. Among the evaluated compounds,
      20c and 30 were found more potent than CQ against K1 and displayed a four-fold
      and a three-fold higher activity respectively, with a good selectivity index
      (SI=5846 and 11,350). All synthesized compounds had resistance index between 1.06
      and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that
      this series of compounds act on heme polymerization target. 

PMID- 24906513
TI  - 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine
      phosphatase 1B.
AB  - Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin
      signaling pathways, and has emerged as an attractive target for the treatment of
      type 2 diabetes and obesity. However, the essential pharmacophore of charged
      phosphotyrosine or its mimetic confer low selectivity and poor cell permeability.
      Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a
      drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first
      time as a novel surrogate of phosphotyrosine. An optimal combination of
      hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif
      afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4
      quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity
      over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3
      carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell
      permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies
      and molecular modeling suggest that the 4-quinolone-3-carboxylates act as
      competitive inhibitors by binding to the PTP1B active site in the WPD loop closed
      conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic
      acid derivatives exhibit improved pharmacological properties over previously
      described PTB1B inhibitors and warrant further preclinical studies. 

PMID- 24906514
TI  - Limiting left-sided catheter dwelling time using 3-D NavX to mark and reaccess
      the left atrium via prior transseptal puncture site.
AB  - INTRODUCTION: Ablations requiring transseptal access to the left heart place
      patients at increased risk for stroke, bleeding, and post-procedural cognitive
      dysfunction and other complications. Diminishing left atrial catheter dwelling
      time may decrease these risks. 3-D NavX can be used to facilitate reaccess of
      transseptal puncture sites to allow catheter removal from the left atrium
      immediately after ablation, with reaccess through the prior transseptal site if
      required. Here, we describe the techniques employed and our experience using 3-D
      NavX to limit left atrial catheter dwelling time by marking and reaccess of the
      left atrium via the previously marked transseptal puncture site, a potentially
      radiation-free technique. METHODS: With the use of 3-D NavX, a right atrial
      geometry is created. The patent foramen ovale is marked by using a standard EP
      catheter, or the transseptal puncture site is marked using 3-D NavX by creating a
      unipolar electrode on the transseptal needle at the time of puncture and at the
      time of catheter withdrawal of the ablation catheter from the left atrium.
      Marking the access site allows the catheter to be removed from the left side of
      the heart immediately after the ablation. If reaccess to the left atrium is
      required, the previously marked transseptal site is used to navigate the ablation
      catheter to reaccess the left atrium. All patients <30 years who had undergone
      this technique were evaluated. Data gathered included patient demographics, need
      for and success of transseptal reaccess, left atrial catheter dwelling time, and
      complications. RESULTS: The transseptal site was marked by 3-D NavX in 54
      patients. We were able to successfully reaccess the transseptal puncture site
      using 3-D guidance in all 10 patients where it was desired. In these 54 patients,
      the complication rate was low with one small post-procedural pulmonary embolism
      and one right bundle branch block. No other complications were noted. The median
      procedure time was 105 min (range 58-446 min), the median total fluoroscopic time
      for the entire procedure was 1.3 min (range 0.0-30.8 min), and the median left
      sided catheter dwelling time was 21 min (range 6-112 min). CONCLUSIONS: In our
      retrospective review, reaccess of transseptal puncture site was reproducible, and
      early removal of the catheter from the left side was without the need for repeat
      transseptal punctures. This technique decreases the time the catheter dwells in
      the left atrium, which could decrease risks such as clotting, bleeding, and
      cognitive dysfunction.

PMID- 24906515
TI  - The radio frequency catheter ablation of inter-fascicular reentrant tachycardia:
      new insights into the electrophysiological and anatomical characteristics.
AB  - INTRODUCTION: Macro-reentrant ventricular tachycardias (VT) utilizing the bundle
      branches and Purkinje fibers have been reported as verapamil sensitive VT
      (idiopathic left VT), bundle branch reentrant VT (BBRT) and inter-fascicular
      reentrant tachycardia (inter-fascicular VT). However, diagnostic confusion exists
      with these VTs due to the difficulty in differentiating between them with
      conventional electrophysiological (EP) studies. The aim of this study was to
      clarify the EP and anatomical entity of inter-fascicular VT, and provide
      successful methods for the radio frequency catheter ablation (RFCA) of inter
      fascicular VT. METHODS AND RESULTS: A total of nine patients were included in
      this study. All patients were diagnosed with idiopathic left VT in the first
      session, and underwent a second session after a failed RFCA. Detailed EP studies
      guided by a three-dimensional (3D) mapping system were performed to further
      analyze the VTs. All VTs were finally diagnosed as inter-fascicular VT. They were
      successfully cured with RFCA targeting the left anterior or posterior fascicle,
      which was regarded as a requisite part of the reentrant circuit of the inter
      fascicular VT, using 3D and fluoroscopic images combined with a detailed EP
      investigation instead of the conventional RFCA method targeting Purkinje
      potentials for the RFCA of idiopathic left VT. CONCLUSIONS: Inter-fascicular VT
      could be misdiagnosed as idiopathic left VT due to the limitations of the
      conventional EP study. Failed RFCA in presumptive idiopathic left VT cases has to
      be carefully investigated by further analysis, and a tailored RFCA strategy
      targeting the requisite portions of the left fascicles in the inter-fascicular VT
      reentrant circuit will be required for the successful elimination of the inter
      fascicular VT.

PMID- 24906517
TI  - Solidarity in the Grandparent-Adult Grandchild Relationship and Trajectories of
      Depressive Symptoms.
AB  - PURPOSE OF THE STUDY: Grandparent-adult grandchild relationships are becoming
      longer and more common, and therefore potentially more influential in the lives
      of individuals. This study examined the influence of solidarity (i.e., affinity,
      contact, and functional exchange) in the grandparent-adult grandchild
      relationship upon the depressive symptoms of both members of the dyad. DESIGN AND
      METHODS: The study used data from the Longitudinal Study of Generations, a survey
      of 3- and 4-generation U.S. families that included 7 waves of data collection
      between 1985 and 2004. The sample was comprised of 374 grandparents and 356 adult
      grandchildren. We analyzed the data using multilevel growth curve models.
      RESULTS: For both grandparents and adult grandchildren, greater affinity reduced
      depressive symptoms and more frequent contact increased symptoms. For
      grandparents only, receiving functional support without also providing it
      increased depressive symptoms. IMPLICATIONS: The average grandparent-adult
      grandchild relationship is a source of both support and strain to both
      generations. These relationships exhibit great diversity, however, with large
      amounts of variation between dyads and within a single dyad over time. We suggest
      how policy makers and practitioners can identify the relational contexts that
      best promote the well-being of members of both generations.

PMID- 24906516
TI  - Examining Rowe and Kahn's Concept of Successful Aging: Importance of Taking a
      Life Course Perspective.
AB  - PURPOSE OF THE STUDY: This article critiques Rowe and Kahn's conceptualization of
      successful aging using tenets of the life course perspective. DESIGN AND METHODS:
      A review and synthesis of the literature on successful aging and studies that use
      a life course perspective. RESULTS: We draw on life course principles that view
      development as a dynamic lifelong process, embedded in historical time and place,
      and influenced by the web of relationships individuals are linked to, as well as
      more distal social structural factors. This discussion questions the relatively
      static nature of Rowe and Kahn's successful aging model, its emphasis on personal
      control over one's later-life outcomes, and neglect of historical and cultural
      context, social relationships, and structural forces in influencing later-life
      functioning. IMPLICATIONS: Caution in using the model in its current formulation
      is needed, and we promote thinking about how successful aging can better align
      with micro- and macrolevel issues through utilization of a life course
      perspective.

PMID- 24906518
TI  - Kinnier Wilson's French connections.

PMID- 24906519
TI  - Conventional versus computer-assisted technique for total knee arthroplasty: a
      minimum of 5-year follow-up of 200 patients in a prospective randomized
      comparative trial.
AB  - In the literature, studies of computer-assisted total knee arthroplasty (TKA)
      after mid-term period are not conclusive and long-term data are rare. In a
      prospective, randomized, comparative study 100 conventional TKAs (group REG) were
      compared with 100 computer-assisted TKAs (group NAV). Minimum follow-up was
      5years. No difference in implant failure was found with 1.1% in group NAV versus
      4.6% in group REG (P=0.368). Group NAV showed a significantly less mean deviation
      of mechanical limb axis (P=0.015), more TKAs (90% versus 81% in group REG) were
      within 3 degrees  varus/valgus and a higher tibial slope and lateral distal
      femoral angle (LDFA) accuracy was found (P<=0.034). Clinical investigational
      parameters showed no differences (P>=0.058). Insall and HSS score total were also
      higher in group NAV (P<=0.016). 

PMID- 24906520
TI  - Recreational runners with patellofemoral pain exhibit elevated patella water
      content.
AB  - Increased bone water content resulting from repetitive patellofemoral joint
      overloading has been suggested to be a possible mechanism underlying
      patellofemoral pain (PFP). To date, it remains unknown whether persons with PFP
      exhibit elevated bone water content. The purpose of this study was to determine
      whether recreational runners with PFP exhibit elevated patella water content when
      compared to pain-free controls. Ten female recreational runners with a diagnosis
      of PFP (22 to 39years of age) and 10 gender, age, weight, height, and activity
      matched controls underwent chemical-shift-encoded water-fat magnetic resonance
      imaging (MRI) to quantify patella water content (i.e., water-signal fraction).
      Differences in bone water content of the total patella, lateral aspect of the
      patella, and medial aspect of the patella were compared between groups using
      independent t tests. Compared with the control group, the PFP group demonstrated
      significantly greater total patella bone water content (15.4+/-3.5% vs. 10.3+/
      2.1%; P=0.001), lateral patella water content (17.2+/-4.2% vs. 11.5+/-2.5%;
      P=0.002), and medial patella water content (13.2+/-2.7% vs. 8.4+/-2.3%; P<0.001).
      The higher patella water content observed in female runners with PFP is
      suggestive of venous engorgement and elevated extracellular fluid. In turn, this
      may lead to an increase in intraosseous pressure and pain. 

PMID- 24906521
TI  - Physical activity and cardiovascular risk factors in a 40- to 42-year-old rural
      Norwegian population from 1975-2010: repeated cross-sectional surveys.
AB  - BACKGROUND: Geographical differences in cardiovascular diseases (CVD) have been
      observed among Norwegian counties. Better long-term health status and higher
      physical activity (PA) levels have been documented in the county of Sogn &
      Fjordane compared with other counties. However, recent trends in CVD risk factors
      have not been documented. The aim of this study was to investigate the secular
      trends in leisure time physical activity (LTPA) and other CVD risk factors over a
      35-year period in a rural population of 40- to 42-year-olds in western Norway and
      to compare these trends with national trends. METHODS: Data from eight cross
      sectional studies from 1975-2010 (n = 375,682) were obtained from questionnaires
      and physical examinations and were analyzed using mixed model regression
      analyses. RESULTS: Decreasing trends were observed for sedentary behavior (for
      women), moderate PA, smoking, systolic blood pressure (SBP), diastolic blood
      pressure (DBP), high-density lipoprotein (HDL-c) and total cholesterol (TC),
      whereas increasing trends were observed for body mass index (BMI), triglycerides
      (TG), light PA, vigorous PA and sedentary behavior for men. Compared to the
      national trends, the trends in the 40-42-year-olds from Sogn & Fjordane were more
      beneficial in terms of TG, HDL-c and BMI but less beneficial in terms of SBP and
      DBP. CONCLUSIONS: Over a 35-year-period, this study indicates that the LTPA level
      has been relatively stable in the county of Sogn & Fjordane. Upward trends were
      observed in light and vigorous PA, whereas a downward trend was observed in
      moderate PA. For sedentary behavior, an upward trend was observed in men, whereas
      a downward trend was observed in women. For smoking, BP and cholesterol
      decreasing trends were found, but increasing trends were observed in BMI and TG.
      Compared with the national data, the trends in Sogn & Fjordane were more
      beneficial for TG, HDL-c and BMI but less beneficial for BP.

PMID- 24906522
TI  - Ratification vote on taxonomic proposals to the International Committee on
      Taxonomy of Viruses (2014).
AB  - Changes to virus taxonomy approved by a vote of all ICTV members in February
      March 2014 are reported. 

PMID- 24906523
TI  - First isolation and characterization of a mosquito-borne orbivirus belonging to
      the species Umatilla virus in East Asia.
AB  - An orbivirus was isolated from a sample from the ornithophilic mosquito Culex
      sasai in Japan. The virus, designated Koyama Hill virus (KHV), replicated to high
      titer in a mosquito cell line and to a low titer in an avian cell line, but the
      release of progeny viruses was not observed in mammalian cell lines inoculated
      with KHV. Electron microscopic examination of KHV-infected mosquito cells showed
      approximately 70-nm virus particles and viral tubules typical of members of the
      genus Orbivirus, family Reoviridae. KHV efficiently replicated in Cx. sasai
      mosquitoes, suggesting a potential vector species for KHV transmission in nature.
      Full-length viral genome sequencing and phylogenetic analysis revealed that KHV
      is closely related to Umatilla virus (UMAV) and Stretch Lagoon orbivirus (SLOV).
      This suggests that KHV is a new member of the species Umatilla virus, an
      orbivirus species not previously observed in East Asia. The KHV genome segment
      encoding NS1 contains a notable sequence deletion and heterogeneity compared with
      a prototype UMAV, which may affect its growth properties and pathogenicity in
      host cells. These results provide new insights into the genetic diversity and
      geographic distribution of members of the species Umatilla virus.

PMID- 24906524
TI  - Thermal inactivation of Alkhumra hemorrhagic fever virus.
AB  - The physico-chemical and biological characteristics of Alkhumra hemorrhagic fever
      virus (AHFV) are not yet known. The present study describes the thermal stability
      of this virus at different temperatures for different periods. The kinetics of
      thermal inactivation were studied, linear regressions were plotted, the Arrhenius
      equation was applied, and the activation energy was calculated accordingly.
      Titers of the residual virus were determined in median tissue culture infective
      dose (TCID50), and the rate of destruction of infectivity at various temperatures
      was determined. Infectivity of AHFV was completely lost upon heating for 3
      minutes at 60  degrees C and for 30 min at 56  degrees C. However, the virus
      could maintain 33.2 % of its titer after heating for 60 min at 45  degrees C and
      32 % of its titer after heating for 60 min at 50  degrees C. In conclusion, AHFV
      is thermo-labile, and its inactivation follows first-order kinetics.

PMID- 24906525
TI  - Canine kobuvirus infections in Korean dogs.
AB  - To investigate canine kobuvirus (CaKoV) infection, fecal samples (n = 59) were
      collected from dogs with or without diarrhea (n = 21 and 38, respectively) in the
      Republic of Korea (ROK) in 2012. CaKoV infection was detected in four diarrheic
      samples (19.0 %) and five non-diarrheic samples (13.2 %). All CaKoV-positive dogs
      with diarrhea were found to be infected in mixed infections with canine distemper
      virus and canine parvovirus or canine adenovirus. There was no significant
      difference in the prevalence of CaKoV in dogs with and without diarrhea. By
      phylogenetic analysis based on partial 3D genes and complete genome sequences,
      the Korean isolates were found to be closely related to each other regardless of
      whether they were associated with diarrhea, and to the canine kobuviruses
      identified in the USA and UK. This study supports the conclusion that CaKoVs from
      different countries are not restricted geographically and belong to a single
      lineage.

PMID- 24906526
TI  - Low infectivity of a novel avian-origin H7N9 influenza virus in pigs.
AB  - We studied the pathogenesis and transmissibility of a novel avian-origin H7N9
      influenza virus in pigs. When pigs were infected with H7N9 influenza virus, they
      did not show any clear clinical signs (such as sneezing, fever and loss of body
      weight), and they shed viruses through their noses for 2 days after infection. No
      transmission occurred between infected and naive pigs. Pigs suffered from mild
      pneumonia, which was accompanied by the induction of inflammatory cytokines and
      chemokines such as IL-8 and CCL1. Taken together, our results suggest that pigs
      may not play an active role in transmitting H7N9 influenza virus to mammals.

PMID- 24906527
TI  - Changes to the Statutes and Subcommittees of the International Committee on
      Taxonomy of Viruses (2014).

PMID- 24906528
TI  - Late radiation-associated dysphagia (late-RAD) with lower cranial neuropathy
      after oropharyngeal radiotherapy: a preliminary dosimetric comparison.
AB  - BACKGROUND AND OBJECTIVES: Late radiation-associated dysphagia (late-RAD) is a
      rare delayed toxicity, in oropharyngeal cancer (OPC) survivors. Prevention of
      late-RAD is paramount because the functional impairment can be profound and
      refractory to standard therapies. The objective of this analysis is to identify
      candidate dosimetric predictors of late-RAD and associated lower cranial
      neuropathies after radiotherapy (RT) or chemo-RT (CRT) for OPC. MATERIALS AND
      METHODS: An unmatched retrospective case-control analysis was conducted. Late-RAD
      cases were identified among OPC patients treated with definitive RT or CRT.
      Controls were selected with minimum of 6 years without symptoms of late-RAD.
      Dysphagia-aspiration related structures (DARS) and regions of interest containing
      cranial nerve paths (RCCNPs) were retrospectively contoured. Dose volume
      histograms were calculated. Non-parametric bivariate associations were analyzed
      with Bonferroni correction and multiple logistic regression models were fit.
      RESULTS: Thirty-eight patients were included (12 late-RAD cases, 26 controls).
      Median latency to late-RAD was 5.8 years (range: 4.5-11.3 years). Lower cranial
      neuropathies were present in 10 of 12 late-RAD cases. Mean superior pharyngeal
      constrictor (SPC) dose was higher in cases relative to controls (median: 70.5 vs.
      61.6 Gy). Mean SPC dose significantly predicted late-RAD (p = 0.036) and related
      cranial neuropathies (p = 0.019). RCCNPs did not significantly predict late-RAD
      or cranial neuropathies. CONCLUSIONS: SPC dose may predict for late-RAD and
      related lower cranial neuropathies. These data, and those of previous studies
      that have associated SPC dose with classical dysphagia endpoints, suggest impetus
      to constrain dose to the SPCs when possible.

PMID- 24906529
TI  - Pneumocephalus: An unusual complication of lumbar arthrodesis. A clinical case
      and literature review.
AB  - Pneumocephalus is an uncommon but serious complication of spinal surgery and its
      management and pathophysiology is not widely recognized. The incidence of
      symptomatic tension pneumocephalus secondary to posterior spinal arthrodesis is
      unknown. CASE REPORT: The case is reported of a rare case of a 41 year old woman
      with diagnosis of L3-L4, L4-L5 disc disease and left disc herniation L4-L5. A
      posterior spinal arthrodesis L3-L5, L3-L4 and L4-L5 discectomies and release of
      the left L5 root, was performed without apparent complications. Twenty-four hours
      after surgery the patient developed generalized headache, neck stiffness, and
      dysarthria. MRI and CT scans revealed a huge pneumocephalus in the subarachnoid
      space, predominantly in the left frontal lobe without midline shift, which
      originated in the lumbar spinal canal. The patient was treated conservatively,
      with progressive neurological improvement after 72 hours, and clinical and
      radiological normalization after 7 days. DISCUSSION: Pneumocephalus is a rare but
      potentially serious complication of spine surgery related in most cases with
      inadvertent dural tear during the operation. Most collections are small, behave
      benign, and respond to conservative therapy. In the present case, an inadvertent
      dural tear, produced a pneumocephalus. A high degree of suspicion is needed to
      make the diagnosis, prompt treatment, as well as remedying the source of air to
      prevent unwanted morbidity and mortality.

PMID- 24906530
TI  - Complement in monoclonal antibody therapy of cancer.
AB  - Monoclonal antibodies (mAb) have been used as targeted treatments against cancer
      for more than a decade, with mixed results. Research is needed to understand mAb
      mechanisms of action with the goal of improving the efficacy of currently used
      mAbs and guiding the design of novel mAbs. While some mAb-induced tumor cell
      killing is a result of direct effects on tumor cell signaling, mAb opsonization
      of tumor cells also triggers activation of immune responses due to complement
      activation and engagement of antibody receptors on immune effector cells. In
      fact, complement has been shown to play an important role in modulating the anti
      tumor activity of many mAb through complement-dependent cytotoxicity, antibody
      dependent cytotoxicity, and through indirect effects by modulating the tumor
      microenvironment. Complement activity can have both agonistic and antagonistic
      effects on these processes. How the balance of such effects impacts on the
      clinical efficacy of mAb therapy remains unclear. In this review, we discuss the
      mAbs currently approved for cancer treatment and examine how complement can
      impact their efficacy with a focus on how this information might be used to
      improve the clinical efficacy of mAb treatment.

PMID- 24906533
TI  - [Driving ability with mental and neurological diseases].

PMID- 24906531
TI  - Neighborhood context and Black heterosexual men's sexual HIV risk behaviors.
AB  - The effects of neighborhood context on sexual risk behavior are understudied,
      particularly for Black heterosexual men who do not inject drugs or report heavy
      drug use. Evidence of a generalized HIV epidemic (>1 %) among Black heterosexuals
      in low-income urban U.S. communities underscores the importance of examining the
      effects of neighborhood context on Black heterosexual men's sexual risk, however.
      We used structural equation modeling to test the pathways between neighborhood
      context (neighborhood disorder, personal violence, neighborhood threats),
      depression, substance use, and sexual risk behavior. Participants were 526 self
      identified Black heterosexual men, ages 18-45, recruited via randomized venue
      based probability sampling in Philadelphia, PA. Analyses of model fit statistics
      from Mplus indicated statistically significant direct pathways between
      neighborhood context, depression, substance use, and sexual risk behavior. The
      total indirect effect of neighborhood context on sexual risk behavior through
      substance use was also significant. The study's results highlight a need for more
      research on neighborhood context and sexual HIV risk, and for multilevel
      interventions to address the effects of negative neighborhood context on Black
      heterosexual men's sexual HIV risk. 

PMID- 24906532
TI  - A mixed-methods study of condom use and decision making among adolescent gay and
      bisexual males.
AB  - Young men who have sex with men have the highest rates of new HIV infections in
      the U.S., but they have been understudied relative to other populations. As a
      formative step for the development of a text messaging HIV prevention
      intervention, this mixed methods study aimed to understand how adolescent gay and
      bisexual males (AGBM) make decisions about condom use and factors that may differ
      based on age, sexual experience, and rural versus urban residency. Four online,
      asynchronous focus groups were conducted with 75 14-18 year old AGBM across the
      U.S. Qualitative analyses uncovered themes related to relationship influences on
      condom use (e.g. marriage, trust), access issues, and attitudes and experiences
      that both encouraged as well as discouraged condom use. Mixed methods analyses
      explored differences between groups in endorsement of themes. For example,
      younger and sexually experienced participants were more likely to report the cost
      of condoms was prohibitive and sexually experienced and rural youth were more
      likely to describe being influenced by emotional aspects of the relationship.
      These data highlight both opportunities for as well as the importance of
      tailoring HIV prevention programs for sub-groups of AGBM.

PMID- 24906534
TI  - [Driving ability with alcohol and drug dependence and schizophrenia].
AB  - Alcohol and drugs use are of great relevance for driving ability. The number of
      alcohol-related accidents with injuries in Germany showed a 40 % decline over the
      past decade (2011: 15,898 including 400 deaths, other drugs 1400). Road surveys
      indicate the risk of accidents to be high in psychostimulant users but only
      medium in opioid users. Guidelines for medical and psychological examinations of
      drunken drivers are given. Alcohol-related questions are the most commonly
      encountered in medical psychological expert opinions with 51 % followed by drugs
      and medications with 21 %. The fundamental principles of expert opinions are
      presented. At last count the proportion of all investigated persons who tested
      positive was 55 %. In the absence of other health-related limitations, most
      patients under substitution therapy for opiate addiction are barely impaired in
      the cognitive functions relevant for driving ability. The database for traffic
      offences and schizophrenia is much worse. Acute psychotic illness rules out
      driving ability. In patients with first onset disease this can usually be granted
      after 1 year of remission from symptoms but in cases of repeated exacerbations
      longer intervals of 3-5 years are warranted. 

PMID- 24906536
TI  - [Driving ability with multiple sclerosis].
AB  - Driving is an important issue for young patients, especially for those whose
      walking capacity is impaired. Driving might support the patient's social and
      vocational participation. The question as to whether a patient with multiple
      sclerosis (MS) is restricted in the ability to drive a car depends on
      neurological and neuropsychological deficits, self-awareness, insight into
      deficits and ability to compensate for loss of function. Because of the enormous
      variability of symptoms in MS the question is highly individualized. A practical
      driving test under supervision of a driving instructor (possibly accompanied by a
      neuropsychologist) might be helpful in providing both patient and relatives
      adequate feedback on driving abilities. 

PMID- 24906535
TI  - [Driving ability with affective disorders and under psychotropic drugs].
AB  - There are only few data available regarding the effects of depressive disorders
      on road safety due to methodological shortcomings. Patients with acute severe
      depression or manias are unqualified for driving but after clinical remission
      driving ability can be attested under psychiatric supervision in most cases. So
      far there are only few data available about a patient's fitness to drive under
      psychotropic medication. Regarding the effects of antidepressants on road safety
      depressed patients obviously benefit from treatment with newer antidepressants;
      however, at least some subgroups of patients do not reach the performance level
      of healthy subjects. Approximately 17 % of remission bipolar patients must be
      regarded as unable to drive and 27 % of patients with schizophrenia on discharge
      from hospital. Benzodiazepines are clearly associated with increased risk of road
      traffic accidents. Impaired driving ability of young attention deficit
      hyperactivity disorder (ADHS) patients is improved under treatment with
      methylphenidate. Counselling patients with respect to driving ability must be
      carried out individually taking into account factors of the illness, personality,
      attitudes and coping strategies as well as different psychopharmacological
      effects. 

PMID- 24906537
TI  - [Assessment of driving in patients with vertigo and dizziness].
AB  - The driving performance of patients with dizziness and vertigo has gained only
      minor attention so far. Patients with permanent vestibular loss or with episodic
      vestibular symptoms can experience difficulties in driving a motor vehicle. The
      presence of a chronic or episodic syndrome presenting with dizziness and/or
      vertigo does not automatically exclude the ability to drive. Assessment of
      driving performance should consider the degree of the deficits and compensation
      in chronic dysfunction and the severity and frequency of attacks, prodromes and
      triggers of symptoms in episodic disorders. 

PMID- 24906538
TI  - [Principles of evaluating driving ability for neurological and psychiatric
      diseases].
AB  - If attending physicians and psychologists recognize restricted or a lack of
      driving ability they are obliged to inform their patients appropriately. In
      Germany the legal basis for assessing driving ability is the "Fahrerlaubnis
      Verordnung" (FeV, driving licence act), supplemented by guidelines for evaluating
      driving ability. In each individual case it has to be clarified whether and to
      what extent permanent or paroxysmally occurring disorders affect driving ability
      and whether lack of insight ability or personality defects are a threat to
      driving safety. In addition, it has to be considered whether compensation
      opportunities exist that enable restricted driving ability. If an expert opinion
      is requested by the driving licence authority in Germany the medical expert must
      have a specific qualification and should not be the attending physician. 

PMID- 24906539
TI  - Adenocarcinoma of the ampulla of Vater: what treatment options are available?
AB  - The scientific literature on adenocarcinoma of the ampulla (papilla) of Vater
      suggests that it either represents a distinct entity or is more closely related
      to small bowel adenocarcinoma than to the biliary malignancies. The ambiguity
      surrounding this rare cancer has kindled research exploring its
      immunohistochemistry aspects and gene expression profiling. While the basis of
      management for resectable disease remains surgical intervention, the role of
      adjuvant chemotherapy is not clear. A recent large phase 3 clinical trial
      conducted in patients with resected ampulla of Vater adenocarcinoma favored
      adjuvant chemotherapy over observation alone. The standards of therapy for the
      advanced small bowel adenocarcinoma and biliary cancer are fluoropyrimidine
      derivatives and gemcitabine-based combinations, respectively. In addition, new
      biologic and targeted agents may enhance clinical results seen in this cancer
      type. Therefore, diligently designed clinical trials are necessary to establish
      its optimal treatment strategies. We describe herein a patient with ampulla of
      Vater adenocarcinoma who had an exceptional response to fluoropyrimidine-based
      chemotherapy. We further include a discussion reviewing the clinicopathologic
      aspects of this neoplasm as well as focus on currently available and future
      therapeutic options.

PMID- 24906541
TI  - The Combination of Elevated Triglycerides and Abnormal Fasting Glucose Increases
      Risk of Cerebral Infarction in Patients With Mild to Moderate
      Hypercholesterolemia: A Post Hoc Analysis of the MEGA Study.
AB  - BACKGROUND: While triglycerides (TGs) and diabetes increase the risk of
      cardiovascular disease (CVD), their combined effects have not been quantified. We
      explored the combined effect of elevated TGs and glucose on CVD in a post hoc
      analysis of the large-scale Management of Elevated Cholesterol in the Primary
      Prevention Group of Adult Japanese (MEGA) Study. MATERIAL AND METHODS: In the
      MEGA Study, 8214 patients with mild to moderate hypercholesterolemia were
      randomly allocated to the diet alone group or diet plus pravastatin group and
      followed for 5 years. Of those, 7832 patients included in the intention-to-treat
      analysis were stratified into 4 groups: abnormal fasting glucose (AFG) plus high
      TGs, high TGs alone, AFG alone, and normal fasting glucose plus normal TGs
      (reference). Cox proportional hazard models were used to compare the incidence of
      and mortality from CVD in the 4 groups. RESULTS: Incidence of CVD and coronary
      heart disease was significantly higher in the groups with AFG alone (hazard ratio
      [HR], 2.02 and 3.38; P < .01, respectively) and AFG plus high TGs (HR, 2.87 and
      3.87; P < .01, respectively) than the reference group. A similar relation was
      found in models adjusting for high-density lipoprotein cholesterol (HDL-C).
      Although the incidence of cerebral infarction was significantly higher only in
      the group with AFG plus high TGs (HR, 2.16; P = .01), it was marginally
      significantly higher than the reference group after adjustment for HDL-C (HR,
      1.86; P = .06). Diet plus pravastatin treatment reduced the risk of cerebral
      infarction by 66% in the group with AFG plus high TGs (P = .03). CONCLUSIONS: Our
      findings contribute to the formulation of the hypothesis that patients with
      hypercholesterolemia having AFG plus high TGs have an increased risk of cerebral
      infarction. These are compatible with the result from the main study that
      patients with hypercholesterolemia randomized to diet plus pravastatin had a
      reduced risk of cerebral infarction.

PMID- 24906540
TI  - Chronic treatment with qiliqiangxin ameliorates aortic endothelial cell
      dysfunction in diabetic rats.
AB  - Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be
      beneficial for chronic heart failure. However, whether QL can also improve
      endothelial cell function in diabetic rats remains unknown. Here, we investigated
      the effect of QL treatment on endothelial dysfunction by comparing the effect of
      QL to that of benazepril (Ben) in diabetic Sprague-Dawley rats for 8 weeks.
      Cardiac function was evaluated by echocardiography and catheterization. Assays
      for acetylcholine-induced, endothelium-dependent relaxation (EDR), sodium
      nitroprusside-induced endothelium-independent relaxation, serum nitric oxide
      (NO), and nitric oxide synthase (NOS) as well as histological analyses were
      performed to assess endothelial function. Diabetic rats showed significantly
      inhibited cardiac function and EDR, decreased expression of serum NO and
      phosphorylation at Ser(1177) on endothelial NOS (eNOS), and impaired endothelial
      integrity after 8 weeks. Chronic treatment for 8 weeks with either QL or Ben
      prevented the inhibition of cardiac function and EDR and the decrease in serum NO
      and eNOS phosphorylation caused by diabetes. Moreover, either QL or Ben
      suppressed inducible NOS (iNOS) protein levels as well as endothelial necrosis
      compared with the diabetic rats. Additionally, QL prevented the increase in
      angiotensin-converting enzyme 1 and angiotensin II receptor type 1 in diabetes.
      Thus, chronic administration of QL improved serum NO production, EDR, and
      endothelial integrity in diabetic rat aortas, possibly through balancing eNOS and
      iNOS activity and decreasing renin-angiotensin system expression. 

PMID- 24906542
TI  - Rapid Induction of Hypothermia by the ThermoSuit System Profoundly Reduces
      Infarct Size and Anatomic Zone of No Reflow Following Ischemia-Reperfusion in
      Rabbit and Rat Hearts.
AB  - INTRODUCTION: Although hypothermia reduces myocardial infarct size, noninvasive
      and rapid cooling methods are lacking. This study tests the effectiveness of a
      novel cooling apparatus on myocardial infarct size and no-reflow area in 2 models
      of coronary artery occlusion (CAO). METHODS AND RESULTS: Animals were randomized
      to normothermic (N) or hypothermic (H) groups after isolation of a proximal
      coronary artery. Animals were subjected to 30 minutes CAO and 3 hours
      reperfusion. In protocol 1 (rabbit, n = 8 per group), hypothermia was initiated,
      using the ThermoSuit apparatus (convective-immersion cooling), 5 minutes after
      the onset of CAO to a goal temperature of ~32 degrees C. In protocol 2 (rat, n =
      5 per group), hypothermia was initiated 2 minutes after the onset of CAO to a
      goal temperature of ~30 degrees C. Goal temperature was reached in ~20 minutes.
      In protocol 1, hypothermia caused an 82% reduction in infarct size as a
      percentage of the ischemic risk zone (N, 44% +/- 5%; H; 8% +/- 2%, P < 0.001) and
      an 89% reduction in the no-reflow area (N, 44% +/- 4%; H, 5% +/- 1%, P < 0.001).
      In protocol 2, hypothermia caused a 73% infarct size reduction (N, 51% +/- 5%; H,
      14% +/- 6%, P < 0.01) and a 99% reduction in the no-reflow area (N, 33% +/- 5%;
      H, 0.4% +/- 0.3%, P < 0.01). CONCLUSION: The ThermoSuit device induced rapid
      hypothermia and limited infarct size and no reflow to the greatest extent ever
      observed in this laboratory with a single intervention.

PMID- 24906543
TI  - Erratum to: Videoendoscopic diagnosis for predicting the response to oral
      appliance therapy in severe obstructive sleep apnea.

PMID- 24906544
TI  - Implications of revised AASM rules on scoring apneic and hypopneic respiratory
      events in patients with heart failure with nocturnal Cheyne-Stokes respiration.
AB  - STUDY OBJECTIVES: This study investigated the implications of the revised scoring
      rules of the American Academy of Sleep Medicine (AASM) in patients with heart
      failure (HF) with Cheyne-Stokes respiration (CSR). METHODS: Ninety-one patients
      (NYHA >=II, LVEF <=45 %; age 73.6 +/- 11.3 years old; 81 male subjects) with
      documented CSR underwent 8 h of cardiorespiratory polygraphy recordings. Those
      were analyzed by a single scorer strictly applying the 2007 recommended, 2007
      alternative, and the 2012 scoring rules. RESULTS: Compared with the AASM 2007
      recommended rules, apnea-hypopnea index (AHI) and hypopnea index (HI) increased
      significantly when the 2007 alternative and 2012 rules were applied (AHI 34.1 +/-
      13.5/h vs 37.6 +/- 13.2/h vs 38.3 +/- 13.2/h, respectively; HI 10.2 +/- 9.4/h vs
      13.7 +/- 10.7/h vs 14.4 +/- 11.0/h, respectively; all p < 0.001). Duration of CSR
      increased significantly with the alternate versus recommended 2007 rules (182.2
      +/- 117.0 vs 170.1 +/- 115.0 min; p <= 0.001); there was a significant decrease
      in CSR duration for the 2012 versus 2007 alternative rules (182.2 +/- 117.0 vs
      166.7 +/- 115.4 min; p <= 0.001). CONCLUSION: AHI was higher using the AASM 2012
      scoring rules due to a less strict definition of hypopnea. Data on the prognostic
      effects of CSR in patients with HF and the benefits of treatment are mostly based
      on the AASM 2007 recommended rules, so differences between these and the newer
      version need to be taken into account.

PMID- 24906545
TI  - A task-oriented circuit training in multiple sclerosis: a feasibility study.
AB  - BACKGROUND: The aim of this study was to evaluate the safety, feasibility and
      preliminary effects of a high-intensity rehabilitative task-oriented circuit
      training (TOCT) in a sample of multiple sclerosis (MS) subjects on walking
      competency, mobility, fatigue and health-related quality of life (HRQoL).
      METHODS: 24 MS subjects (EDSS 4.89 +/- 0.54, 17 female and 7 male, 52.58 +/-
      11.21 years, MS duration 15.21 +/- 8.68 years) have been enrolled and randomly
      assigned to 2 treatment groups: (i) experimental group received 10 TOCT sessions
      over 2 weeks (2 hours/each session) followed by a 3 months home exercise program,
      whereas control group did not receive any specific rehabilitation intervention. A
      feasibility patient-reported questionnaire was administered after TOCT.
      Functional outcome measures were: walking endurance (Six Minute Walk Test), gait
      speed (10 Meter Walk Test), mobility (Timed Up and Go test) and balance (Dynamic
      Gait Index). Furthermore, self-reported questionnaire of motor fatigue (Fatigue
      Severity Scale), walking ability (Multiple Sclerosis Walking Scale - 12) and
      health-related quality of life (Multiple Sclerosis Impact Scale - 29) were
      included. Subjects' assessments were delivered at baseline (T0), after TOCT (T1)
      and 3 months of home-based exercise program (T2). RESULTS: After TOCT subjects
      reported a positive global rating on the received treatment. At 3 months, we
      found a 58.33% of adherence to the home-exercise program. After TOCT, walking
      ability and health-related quality of life were improved (p < 0.05) with minor
      retention after 3 months. The control group showed no significant changes in any
      variables. CONCLUSIONS: This two weeks high-intensity task-oriented circuit class
      training followed by a three months home-based exercise program seems feasible
      and safe in MS people with moderate mobility impairments; moreover it might
      improve walking abilities. TRIAL REGISTRATION: NCT01464749.

PMID- 24906546
TI  - Modeling distinct imaging hemodynamics early after TBI: the relationship between
      signal amplitude and connectivity.
AB  - Over the past decade, fMRI studies of cognitive change following traumatic brain
      injury (TBI) have investigated blood oxygen level dependent (BOLD) activity
      during working memory (WM) performance in individuals in early and chronic phases
      of recovery. Recently, BOLD fMRI work has largely shifted to focus on WM and
      resting functional connectivity following TBI. However, fundamental questions in
      WM remain. Specifically, the effects of injury on the basic relationships between
      local and interregional functional neuroimaging signals during WM processing
      early following moderate to severe TBI have not been examined. This study employs
      a mixed effects model to examine prefrontal cortex and parietal lobe signal
      change during a WM task, the n-back, and whether there is covariance between
      regions of high amplitude signal change, (synchrony of elicited activity (SEA)
      very early following TBI. We also examined whether signal change and SEA
      differentially predict performance during WM. Overall, percent signal change in
      the right prefrontal cortex (rPFC) was and important predictor of both reaction
      time (RT) and SEA in early TBI and matched controls. Right prefrontal cortex
      (rPFC) percent signal change positively predicted SEA within and between persons
      regardless of injury status, suggesting that the link between these neurodynamic
      processes in WM-activated regions remains unaffected even very early after TBI.
      Additionally, rPFC activity was positively related to RT within and between
      persons in both groups. Right parietal (rPAR) activity was negatively related to
      RT within subjects in both groups. Thus, the local signal intensity of the rPFC
      in TBI appears to be a critical property of network functioning and performance
      in WM processing and may be a precursor to recruitment observed in chronic
      samples. The present results suggest that as much research moves toward large
      scale functional connectivity modeling, it will be essential to develop
      integrated models of how local and distant neurodynamics promote WM performance
      after TBI. 

PMID- 24906547
TI  - Gender differences in healthy life expectancy among Brazilian elderly.
AB  - BACKGROUND: This study examined gender differences in healthy life expectancy
      (HLE) and unhealthy life expectancy (UHLE) among people aged 60 years or older
      living in a large Brazilian city. METHODS: Based on Chiang method, abridged life
      tables were constructed for men and for women. To calculate HLE, the Sullivan
      method was applied. Estimates of the prevalence of self-rated health and self
      reported functional disability (global, mild/moderate, and severe) were obtained
      from a population-based household survey carried out in 2008, which involved non
      institutionalized individuals. RESULTS: Findings showed that women live longer
      and these extra years would be spent in good self-rated health. For example,
      women aged 60 would live, on average, 4 more years in good health in comparison
      to men. In terms of global limitations and mild/moderate limitations, no gender
      differences were detected for HLE. However, UHLE was statistically higher among
      women than among men at all ages in the global limitations and mild/moderate
      limitations (except for the age 80). Women at age 60, for instance, could expect
      to live 3.1 years longer with mild/moderate limitations compared to men. Gender
      differences were identified for severe limitations for either HLE or UHLE. In
      comparison to men, women at age 60, for example, would expect to live 2.5 and 2.0
      more years without and with severe limitations. CONCLUSIONS: By showing that the
      advantage of longer life expectancy among women is not necessarily accompanied by
      worse health conditions, these findings add some evidence to the debate about
      male-female health-survival paradox. Policy efforts are necessary to reduce
      gender differences in the quantity and quality of years to be lived, providing
      equal opportunities to women and men live longer with quality of life, autonomy,
      and independence.

PMID- 24906548
TI  - Why perform colonoscopy following acute diverticulitis of the colon?

PMID- 24906549
TI  - Placental pathologic changes of maternal vascular underperfusion in
      bronchopulmonary dysplasia and pulmonary hypertension.
AB  - INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the most common chronic lung
      disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious
      complication that can negatively impact later childhood health. There is growing
      evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia
      ischemia. The purpose of this study was to investigate whether placental
      pathologic changes of maternal vascular underperfusion (MVU) are associated with
      BPD, and further increased with PH. METHODS: We conducted a 5-year retrospective
      cohort study of premature infants born <=28 weeks. BPD was defined as persistent
      oxygen requirement at 36 weeks corrected gestational age. PH was identified using
      a standardized algorithm of echocardiogram review. Archived placental slides
      underwent standardized masked histopathologic review. Logistic regression
      modeling was performed, taking into account important maternal and infant
      covariates. RESULTS: Among 283 births, 121 had MVU, of which 67 (55%) developed
      BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme
      prematurity, BPD was the only outcome that was increased with MVU (P < 0.001).
      After adjustment for birth weight, fetal growth restriction, preeclampsia and
      other factors, infants with MVU were more likely to develop BPD (adjusted odds
      ratio = 2.6; 95% confidence interval = 1.4, 4.8). Certain MVU sublesions
      (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal
      villi) were increased with PH (P < 0.001). DISCUSSION: Placental MVU may identify
      BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases
      their risk for development of PH disease. CONCLUSIONS: Our findings have
      important implications for providing earlier and more effective therapies for
      BPD.

PMID- 24906551
TI  - Functional and patient-reported outcome of partial wrist denervation versus the
      Mannerfelt wrist arthrodesis in the rheumatoid wrist.
AB  - INTRODUCTION: Wrist arthrodesis offers high success rates in patients with
      rheumatoid arthritis; however, loss of residual mobility may cause unnecessary
      disability. This makes wrist denervation an appealing alternative. However, there
      is a distinct lack of patient-reported outcome measure studies comparing these
      two procedures. The aim of this study was to report any change in function, pain
      and satisfaction following wrist arthrodesis compared to denervation in a single
      surgeon series of rheumatoid patients. PATIENTS AND METHODS: The results of 16
      wrist arthrodesis in 15 patients and 14 partial (PIN) wrist denervations in 13
      patients were compared with a mean follow-up period of 39 and 22 months,
      respectively. The primary outcome measures were the same for both groups and
      included the validated patient-rated wrist evaluation questionnaire and a
      satisfaction questionnaire. RESULTS: Wrist arthrodesis significantly improved the
      mean total pain and functional outcome scores by 54 and 36 %, respectively, at
      the time of follow-up. Wrist denervation patients also reported significant
      improvements of 44 and 42 % in total pain and functional outcomes, respectively;
      87 % reported being very satisfied with their wrist arthrodesis procedure
      compared to 78 % in the denervation group. No statistically significant
      difference in response between the groups was observed in this series of
      patients. CONCLUSIONS: Both procedures enjoyed favourable results amongst
      patients with excellent satisfaction outcomes. PIN denervation is a simple
      procedure with low complication rates and we therefore consider it a valid
      alternative to more difficult treatment options, such as partial or total wrist
      arthrodesis.

PMID- 24906550
TI  - Body weight dissatisfaction before, during and after pregnancy: a comparison of
      women with and without eating disorders.
AB  - PURPOSE: We examined prospectively changes in current BMI and body weight
      dissatisfaction in women with and without eating disorders (EDs) during and after
      pregnancy compared to prepregnancy. METHODS: We assessed pregnant women with (ED
      group, N = 18) and without an ED (Control group, N = 129) using current BMI and
      the discrepancy between current and desired BMI (body weight dissatisfaction).
      This is a measure representative of overall body dissatisfaction. Women were
      assessed retrospectively for prepregnancy, and prospectively at weeks 12-14
      (first trimester), weeks 24-26 (second trimester) and weeks 34-36 (third
      trimester) during pregnancy and 3, 6 and 12 months after. RESULTS: Compared with
      prepregnancy, current BMI for the ED group increased at trimester two and three
      and returned to prepregnancy levels postpartum, while current BMI for the Control
      group increased at trimester one, two, three, and remained above their
      prepregnancy BMI at 3, 6 and 12 months postpartum. Compared with prepregnancy
      levels, body weight dissatisfaction for the ED group improved at 6 and 12 months
      postpartum, while body weight dissatisfaction for the Control group increased at
      trimester two and three, and remained greater at 3 and 6 months postpartum before
      returning to prepregnancy levels at 12 months postpartum. Maximum dissatisfaction
      occurs in trimester three for both the ED (mean 2.98, SD 2.74) and Control groups
      (mean 2.93, SD 3.22). CONCLUSIONS: Body dissatisfaction does not improve during
      pregnancy in women with or without EDs. Body weight dissatisfaction remained
      unchanged for women with EDs during pregnancy, before a decrease at 6 and 12
      months postpartum. Body weight dissatisfaction increased for women without EDs,
      and remained elevated until 6 months postpartum. Despite this, women with and
      without EDs gained significant weight during pregnancy This suggests all women
      require information and support regarding body image during the pregnancy and in
      the 12 months postpartum.

PMID- 24906552
TI  - Young age at first intercourse and subsequent risk-taking behaviour: An
      epidemiological study of more than 20,000 Danish men from the general population.
AB  - AIM: First intercourse at the age of 14 years or younger is usually considered
      high-risk behaviour for sexually transmitted infections (STIs). It has been
      linked to other types of risky behaviour in women, while conflicting results have
      been obtained for men. The aim of the study was to estimate the prevalence of
      first intercourse at a young age in various birth cohorts of men and to determine
      any association with later risky behaviour. METHODS: We studied 22,979 randomly
      selected men aged 18-45 years from the Danish general male population who
      responded to a self-administered questionnaire. Multiple sexual partners over a
      lifetime, multiple new sexual partners within the past 6 months, intercourse with
      a commercial sex worker, having an STI, binge drinking and current smoking were
      considered risky behaviour. RESULTS: First intercourse at the age of 14 years or
      younger was more prevalent in younger (14%) than in older (10%) birth cohorts and
      among men with shorter schooling. Young age at sexual debut was associated with a
      more than twofold increase in the risks for subsequent risky behaviour.
      CONCLUSIONS: More than 10% of Danish men first had sex at an early age, and this
      was closely related to subsequent risk-taking behaviour.

PMID- 24906553
TI  - Informal patient payments in publicly financed healthcare facilities in
      Lithuania.
AB  - BACKGROUND: Since the late 1990s Lithuania has had a mixed, solidary based
      healthcare system, predominantly funded from the National Health Insurance Fund
      through a compulsory health insurance scheme. The cultural tradition of informal
      payments in healthcare in Lithuania was inherited from the Soviet past and is
      still alive. AIM: This study reveals the extent and nature of informal patient
      payments, and identifies the motivation behind those payments occurring in
      publicly financed healthcare facilities in Lithuania. METHODS: The quantitative
      household survey design was chosen for this study. The randomly selected sample
      was comprised of inhabitants aged 18 years and older, representing the entire
      population of Lithuania by county, place of residence (urban and rural), age and
      sex. The study sample consisted of 1067 participants interviewed in 2009 and
      2010, and 1068 in 2011 (response rate ranged from 66.6% to 68.2%). RESULTS: Users
      of healthcare services usually made informal payments for the visit to, and
      consultation with, a general practitioner or physician specialist and for
      diagnostic services. Females and older citizens, the disabled, public/private
      sector employees, retirees, those with higher education and those in the highest
      household monthly income group were more prone to pay informally for health
      services. The majority of respondents were against formalization of informal
      patient payment. CONCLUSIONS: National health insurance payments for healthcare
      services from the formal public fund for healthcare are further augmented by
      informal payments from service consumers, used routinely for better access to and
      higher quality of healthcare service.

PMID- 24906554
TI  - Sickness benefit cuts mainly affect blue-collar workers.
AB  - AIMS: To analyse the impact of sick-pay cuts on the use of sickness absence by
      employees of different socioeconomic groups. In 2009 cuts in sick pay were
      implemented in reaction to an economic crisis in Estonia. METHODS: Nationwide
      health survey data from the years 2004, 2006, 2008, and 2010 were used to
      evaluate sickness absence among blue-collar and white-collar workers. The dataset
      comprised 7,449 employees of 20-64 years of age. Difference in prevalence of
      absentees before and after the reform was assessed using the chi-squared test.
      Odds ratios (OR) for sickness absence were calculated in a multivariate logistic
      regression model. RESULTS: After the reform, the proportion of blue-collar
      workers who had been on sick leave decreased from 51% to 40% (p<0.001) and among
      white-collar employees from 45% to 41% (p=0.026). This reduction had a similar
      pattern in all the subgroups of blue-collar employees as stratified according to
      gender, age, self-rated health, and presence of chronic disease, especially among
      those with low incomes; in white-collar employees it reached statistical
      significance only in those with good self-rated health (p=0.033). In a
      multivariate model the odds of having lower sickness absence were highly
      significant only in blue-collar employees (OR 0.63; 95% confidence interval 0.51
      0.77, p<0.001). CONCLUSIONS: The cuts in sickness benefits had a major impact on
      the use of sickness absence by blue-collar employees with low salaries. This
      indicates that lower income was a major factor hindering the use of sick leave as
      these employees are most vulnerable to the loss of income.

PMID- 24906555
TI  - Yin-Yang strands of PCAF/Hedgehog axis in cancer control.
AB  - PCAF (p300/CBP associated factor) harbors acetyltransferase and a recently
      identified ubiquitylation activity that regulates gene expression in response to
      genotoxic stress or mitogenic signals. We highlight the dual role of PCAF in the
      control of Hedgehog signaling, a master regulator of tissue development,
      stemness, and tumorigenesis. By promoting histone acetylation at Hedgehog/GLI1
      target gene promoters or direct ubiquitylation and proteolysis of GLI1, the
      PCAF/GLI1 axis stands as a promising therapeutic target for Hedgehog-dependent
      tumors. 

PMID- 24906556
TI  - Clinical outcome of lower esophageal sphincter- and vagus-nerve-preserving
      partial cardiectomy for early gastric cancer of the subcardia.
AB  - BACKGROUND: No definitive operative method has been established for the treatment
      of early subcardial gastric cancer. Our newly developed technique involves local
      resection of the subcardia while preserving the lower esophageal sphincter and
      vagus nerve. A new fornix is constructed to accept the transposed esophagus.
      METHODS: Thirty patients underwent this procedure between July 2003 and December
      2010. Continuous gastric pH monitoring was performed immediately after surgery,
      and esophageal manometry was undertaken 1 month later. Serum total protein,
      albumin, total cholesterol, cholinesterase, and body mass index (BMI) were
      recorded every 3 months. Pre- and postoperative oral intake were compared, reflux
      symptoms were recorded, and reflux esophagitis was assessed by endoscopy after 1
      year. RESULTS: Twenty-five patients (86 %) reported no symptoms of reflux, and 27
      (92.8 %) patients could eat 70 % or more of what they had eaten before surgery.
      Lower esophageal pressures were found to be >10 mmHg in 66.7 % of patients, and
      the fraction of time that pH <4 was <5 % of the 24-h monitoring period in 70 %.
      Serum parameters and BMI were unchanged. CONCLUSIONS: This surgical technique is
      a useful means of preserving postoperative quality of life after local
      gastrectomy by preventing reflux and maintaining nutritional status.

PMID- 24906557
TI  - Critical factors that influence the early outcome of laparoscopic total
      gastrectomy.
AB  - BACKGROUND: Laparoscopic distal gastrectomy (LDG) is a routinely performed
      procedure. However, clinical expertise in laparoscopic total gastrectomy (LTG) is
      insufficient, and it is only performed at specialized institutions. This study
      aimed to identify critical factors associated with complications after
      laparoscopic gastrectomy (LG), particularly LTG. METHODS: A large-scale database
      was used to identify critical factors influencing the early outcomes of LTG. Of
      1248 patients with resectable gastric cancer who underwent LG, 259 underwent LTG.
      Predictive risk factors were determined by analyzing relationships between
      clinical characteristics and postoperative complications. Major complications
      after LTG were analyzed in detail. RESULTS: Multivariate analysis of all LG
      procedures revealed LTG as a risk factor for complications. Morbidity in the LDG
      and LTG groups was 6.2 % (52 of 835 patients) and 22.4 % (58 of 259 patients),
      respectively. Major post-LTG complications included anastomotic leakages and
      pancreatic fistulae. The rate of anastomotic leakage was significantly higher in
      the LTG group (5.0 %) than in the LDG group (1.2 %); however, it showed a
      tendency to decrease in more recent cases. Pancreatic fistulae occurred
      frequently after LTG with D2 lymphadenectomy (LTG-D2), particularly in cases of
      concomitant pancreatosplenectomy. Obesity was also associated with pancreatic
      fistula formation after LTG with pancreatosplenectomy. CONCLUSIONS: Compared with
      LDG, LTG is a developing procedure. Advances in the surgical techniques
      associated with the LTG procedure will improve the short-term outcomes of
      esophagojejunostomy. With regard to LTG-D2, establishing optimal and safe #10
      node dissection is one of the most urgent issues. Pancreatic fistula after LTG
      with pancreatosplenectomy must be investigated in the future.

PMID- 24906558
TI  - The National Cancer Institute's Health Information National Trends Survey
      [HINTS]: a national cross-sectional analysis of talking to your doctor and other
      healthcare providers for health information.
AB  - BACKGROUND: The need to understand preferred sources of health information
      remains important to providing patient-centered care. The Internet remains a
      popular resource for health information, but more traditional sources may still
      be valid for patients during a recent health need. This study sought to
      understand the characteristics of patients that turn to their doctor or
      healthcare provider first for a recent health or medical information need.
      METHODS: Using the national cross-sectional survey, Health Information National
      Trend Study [HINTS], characteristics of those who sought a doctor or healthcare
      provider for a recent health information need were compared to other sources.
      Weighted survey responses from Cycle 1 and Cycle 2 of the HINTS survey were used
      for multivariable logistic regression. RESULTS: A total 5,307 patient responses
      were analyzed. Overall, those who seek a doctor or healthcare provider first for
      a health need are female, 46-64 years, White non-Hispanic, educated, in good
      health and users of the Internet. Yet, adjusted logistic regressions showed that
      those who sought a doctor or healthcare provider first during a recent health
      information need compared to other sources were most likely to be 65+ years, in
      poor health, less educated and have health insurance. CONCLUSIONS: Patients who
      seek their doctor or healthcare provider first for health information rather than
      other sources of information represent a unique population. Doctors or healthcare
      providers remain an important resource for these patients during recent needs,
      despite the wide use of the Internet as a source of health information.

PMID- 24906559
TI  - Radiological and pathological characteristics of giant cell tumor of bone treated
      with denosumab.
AB  - We describe a case of giant cell tumor of the proximal tibia with skip bone
      metastases of the ipsilateral femur in a 20-year-old man. After the neoadjuvant
      treatment with denosumab, plain radiographs and computed tomography showed marked
      osteosclerosis and sclerotic rim formation, and 18F-FDG PET/CT showed a decreased
      standardized uptake value, whereas magnetic resonance imaging showed diffuse
      enhancement of the tumor, nearly the same findings as those at pretreatment.
      Pathological findings of the surgical specimen after the denosumab treatment
      showed benign fibrous histiocytoma-like features with complete disappearance of
      both mononuclear stromal cells and multinuclear osteoclast-like giant cells.
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1090602085125068.

PMID- 24906560
TI  - Characterization of the lipoxygenase (LOX) gene family in the Chinese white pear
      (Pyrus bretschneideri) and comparison with other members of the Rosaceae.
AB  - BACKGROUND: Lipoxygenases (LOXs), a type of non-haem iron-containing dioxygenase,
      are ubiquitous enzymes in plants and participate in the formation of fruit aroma
      which is a very important aspect of fruit quality. Amongst the various aroma
      volatiles, saturated and unsaturated alcohols and aldehydes provide the
      characteristic aroma of the fruit. These compounds are formed from unsaturated
      fatty acids through oxidation, pyrolysis and reduction steps. This biosynthetic
      pathway involves at least four enzymes, including LOX, the enzyme responsible for
      lipid oxidation. Although some studies have been conducted on the LOX gene family
      in several species including Arabidopsis, soybean, cucumber and apple, there is
      no information from pear; and the evolutionary history of this gene family in the
      Rosaceae is still not resolved. RESULTS: In this study we identified 107 LOX
      homologous genes from five Rosaceous species (Pyrus bretschneideri, Malus *
      domestica, Fragaria vesca, Prunus mume and Prunus persica); 23 of these sequences
      were from pear. By using structure analysis, phylogenic analysis and collinearity
      analysis, we identified variation in gene structure and revealed the phylogenetic
      evolutionary relationship of this gene family. Expression of certain pear LOX
      genes during fruit development was verified by analysis of transcriptome data.
      CONCLUSIONS: 23 LOX genes were identified in pear and these genes were found to
      have undergone a duplication 30-45 MYA; most of these 23 genes are functional.
      Specific gene duplication was found on chromosome4 in the pear genome. Useful
      information was provided for future research on the evolutionary history and
      transgenic research on LOX genes.

PMID- 24906561
TI  - Emotion work among pregnant and birthing women.
AB  - BACKGROUND: previous research has examined emotional labour as an important
      component of the occupational work of midwives and gynaecological nurses. Fewer
      studies explore emotion work by women during normal pregnancy and birth, and
      existing studies emphasise emotion work based on the midwife-woman relationship.
      This study explores use of emotion work during pregnancy and birth among a sample
      of women. OBJECTIVE: the study objective is to identify the mechanisms and
      purposes of emotion work among women during pregnancy and birth. DESIGN: data
      consist of 18 in-depth interviews with women regarding their pregnancy and birth
      experiences and seven online pregnancy journals. Data were analysed to identify
      themes in participant's descriptions of emotion work during pregnancy and birth.
      FINDINGS: participants described four methods of emotion work that included
      shifting cognitive focus, exerting control, social support and using technology.
      Participants used emotion work for the four main purposes of maintaining their
      own and their babies' health, coping with negative events, managing pain, and
      achieving their desired birth. Although some emotion work was undertaken in
      relational context with the midwife or partner, much of the emotion work
      described took place in solitude. IMPLICATIONS FOR PRACTICE: social support from
      midwives or partners was a form of emotion work that facilitated positive
      interpretations of the birth experience.

PMID- 24906562
TI  - A meta-synthesis of fathers' experiences of their partner's labour and the birth
      of their baby.
AB  - OBJECTIVE: to develop greater understanding of how expectant fathers experience
      their partner's labour and the subsequent birth of their baby. DESIGN: a
      qualitative meta-synthesis. Data were search for in CINAHL, PubMed, Psych Info
      and SCOPUS. SETTING: eight studies conducted in England, Malawi, Nepal and Sweden
      were included. PARTICIPANTS: 120 fathers with experiences of their partner having
      a spontaneous vaginal, assisted or surgical birth. MEASUREMENTS AND FINDINGS: 1st
      order themes were identified and subsequently grouped into seven 2nd order
      themes. Finally through a process of exploring patterns and connections seven 3rd
      order themes were developed which produced new insights into the men's
      experiences of labour and birth. This meta-synthesis revealed that most men
      wanted to be actively involved in their partner's labour, present at the birth
      and respected for what they could contribute. Men recognised that birth was a
      unique event that may be potentially challenging requiring a level of
      preparation. There were also men who felt pressured to attend. During the actual
      experience of labour men commonly expressed overwhelming feelings and inadequacy
      in their ability to support their partner. They particularly struggled with the
      'pain' of labour. Midwives were subsequently identified as best placed to make a
      significant difference to how men perceived their experiences of labour and what
      they described as the life changing event of birth. KEY CONCLUSIONS: the
      expectant fathers' birth experiences were multidimensional. Many were committed
      to being involved during labour and birth but often felt vulnerable. Being
      prepared and receiving support were essential elements of positive experience as
      well as contributing to their ability to adequately support the labouring woman.
      IMPLICATIONS FOR PRACTICE: men's ability to actively prepare for, and be
      supported through, the labour and birth process influences their perceptions of
      the childbirth event as well as their sense of connection to their partner.
      Couples should be given opportunities to explore expectations and how these may
      influence their own construction of their role during the birth process. While
      the role of expectant fathers in labour and birth should be facilitated and
      supported arguably their wish not to participate should be afforded the same
      respect.

PMID- 24906563
TI  - Dual effects of respiratory syncytial virus infections on airway inflammation by
      regulation of Th17/Treg responses in ovalbumin-challenged mice.
AB  - We investigated the effects of respiratory syncytial virus (RSV) infections on
      ovalbumin (OVA)-challenged mice via regulation of Th17/Treg cell responses.
      BALB/c mice were challenged with OVA, followed by RSV infections twice. In OVA
      challenged mice, the secretion of Th2/Th17-type cytokines, airway
      hyperresponsiveness and inflammation were significantly inhibited by initial RSV
      infection. Moreover, the in vivo findings demonstrated that initial RSV infection
      reversed the imbalance of Th17/Treg responses. In contrast, RSV re-infection
      strengthened Th2/Th17-type cytokine secretion, airway hyperresponsiveness, and
      inflammation, especially for lymphocyte infiltration in OVA-challenged mice.
      Meanwhile, RSV re-infection enhanced the imbalanced Th17/Treg responses. Upon all
      results reveal that RSV-induced respiratory infections may lead to dual effects
      pertaining to allergic airway inflammation by regulation of Th17/Treg responses. 

PMID- 24906564
TI  - Decreased flow-mediated dilatation in patients with systemic lupus erythematosus:
      a meta-analysis.
AB  - Premature atherosclerosis, the hallmark of cardiovascular diseases, has been
      found to be a significant cause of late deaths in systemic lupus erythematosus
      (SLE) patients. Therefore, early identification of atherosclerosis before the
      overt disease is curial for the management program of SLE. Flow-mediated
      dilatation (FMD%) is a reliable, noninvasive, easy to use, reproducible, and
      pathogenically relevant index for early atherosclerosis. In recent years, a
      number of studies have been performed to compare the mean FMD% difference between
      patients with SLE and healthy controls. However, these studies have shown
      inconclusive or even contradictory findings. In this study, to derive a more
      precise comparison of FMD% difference between SLE patients and healthy controls,
      a meta-analysis was performed. Databases were searched to identify all available
      studies comparing FMD% between SLE patients and healthy controls. The study
      eligibility criteria were cohort or case-control studies with data on both
      patients diagnosed with SLE and healthy controls, and use of high-resolution
      ultrasonography to detect FMD. Random effect meta-analysis was conducted to
      evaluate the overall mean FMD% difference between the two groups. Publication
      bias was detected by funnel plot and Egger's test. Meta-regression analysis was
      performed to investigate the potential influencing factors on FMD% difference. Of
      the 434 articles initially identified, 22 were finally included in the meta
      analysis. Compared to healthy controls, SLE patients had significantly lower FMD%
      (standardized mean difference, -1.19; 95% CI, -1.63, -0.74; P < 0.001). There was
      significant heterogeneity among these studies (I (2) = 94.3%, P < 0.001), which
      was mainly due to variations in disease duration of SLE patients. The funnel plot
      showed a skewed shape, indicating a marked publication bias, which was further
      supported by the Egger's test (P = 0.006). However, after the correction for
      potential publication bias by using the trim-and-fill method, the main results
      for all studies combined were still significant (P < 0.001). Taken together,
      these findings support the current evidence on a higher cardiovascular burden in
      SLE and support using FMD% as a surrogate for premature atherosclerosis in SLE
      patients.

PMID- 24906566
TI  - Baseline metabolic tumour volume in Hodgkin lymphoma: the prognostic value of
      accessory cells.

PMID- 24906565
TI  - Twelve-year experience of radioembolization for colorectal hepatic metastases in
      214 patients: survival by era and chemotherapy.
AB  - PURPOSE: The aim of this study was to analyze the safety, treatment
      characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for
      unresectable colorectal carcinoma (CRC) liver metastases refractory to standard
      of care therapy. METHODS: A total of 214 patients with CRC metastases were
      treated with Y90 radioembolization over 12 years. Toxicity was assessed using
      National Cancer Institute common terminology criteria. Overall survival was
      analyzed from date of diagnosis of primary cancer, hepatic metastases and from
      the first Y90. Uni/multivariate analyses were performed. Substratification by era
      of chemotherapeutics was performed. RESULTS: Most patients were male (60 %) and
      <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3
      lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11
      %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP
      toxicities were observed in 5 % and 3 % of patients, respectively. Median overall
      survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary
      cancer, hepatic metastases and first Y90, respectively. Survival was
      significantly longer in patients: (1) who received <=2 cytotoxic drugs (n = 104)
      than those who received 3 (n = 110) (15.2 vs. 7.5 months, p = 0.0001); and (2)
      who received no biologic agents (n = 52) compared with those that did (n = 162)
      (18.6 vs. 9.4 months, p = 0.0001). Multivariate analyses identified <=2 cytotoxic
      agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of
      extrahepatic disease and albumin >3 g/dL as independent predictors of survival.
      CONCLUSION: In this largest metastatic CRC series published to date, Y90
      radioembolization was found to be safe; survival varied by prior therapy. Further
      studies are required to further refine the role of Y90 in metastatic CRC.

PMID- 24906567
TI  - Factors influencing U.S. canine heartworm (Dirofilaria immitis) prevalence.
AB  - BACKGROUND: This paper examines the individual factors that influence prevalence
      rates of canine heartworm in the contiguous United States. A data set provided by
      the Companion Animal Parasite Council, which contains county-by-county results of
      over nine million heartworm tests conducted during 2011 and 2012, is analyzed for
      predictive structure. The goal is to identify the factors that are important in
      predicting high canine heartworm prevalence rates. METHODS: The factors
      considered in this study are those envisioned to impact whether a dog is likely
      to have heartworm. The factors include climate conditions (annual temperature,
      precipitation, and relative humidity), socio-economic conditions (population
      density, household income), local topography (surface water and forestation
      coverage, elevation), and vector presence (several mosquito species). A baseline
      heartworm prevalence map is constructed using estimated proportions of positive
      tests in each county of the United States. A smoothing algorithm is employed to
      remove localized small-scale variation and highlight large-scale structures of
      the prevalence rates. Logistic regression is used to identify significant factors
      for predicting heartworm prevalence. RESULTS: All of the examined factors have
      power in predicting heartworm prevalence, including median household income,
      annual temperature, county elevation, and presence of the mosquitoes Aedes
      trivittatus, Aedes sierrensis and Culex quinquefasciatus. Interactions among
      factors also exist. CONCLUSIONS: The factors identified are significant in
      predicting heartworm prevalence. The factor list is likely incomplete due to data
      deficiencies. For example, coyotes and feral dogs are known reservoirs of
      heartworm infection. Unfortunately, no complete data of their populations were
      available. The regression model considered is currently being explored to
      forecast future values of heartworm prevalence.

PMID- 24906568
TI  - Inflammatory bowel diseases increase future ischemic stroke risk: a Taiwanese
      population-based retrospective cohort study.
AB  - BACKGROUND AND AIMS: This cohort study assessed the association between
      inflammatory bowel disease (IBD) and the risk of future ischemic stroke. METHODS:
      The IBD cohort comprised adult patients (>= 20years old) who had received either
      ambulatory or inpatient care between 1998 and 2011 and IBD-free controls were
      randomly selected from the general population and frequency matched according to
      age, sex, and index year (included 18,392 patients with IBD and 73,568 control
      patients). Both cohorts with ischemic stroke before the index date and the
      ischemic stroke cases diagnosed within one year after the index date were
      excluded. We observed the study patients until the incidence of ischemic stroke,
      death, withdrawal from the insurance program, or they were lost to follow-up, or
      the end of 2011. RESULTS: The risk of ischemic stroke was 1.12-fold (95% CI, 1.02
      1.23) higher among the IBD cohort than among the non-IBD cohort. Compared to the
      subjects without IBD, the adjusted HR of ischemic stroke was 1.15 (95% CI 1.04
      1.28) in the Crohn's disease (CD) patients and 1.01 (95% CI 0.84-1.21) in the
      ulcerative colitis (UC) group. The risk of developing ischemic stroke
      significantly increased with the increased frequency of IBD exacerbation and
      hospitalization. Furthermore, the adjusted HR among the CD patients increased in
      conjunction with the number of medical visits, from 1.07 to 6.36 and the adjusted
      HR among the UC patients also increased in conjunction with the number of medical
      visits, from 1.11 to 2.10. CONCLUSIONS: IBD exhibited an increased risk of
      developing ischemic stroke.

PMID- 24906569
TI  - Gluconic acid-producing Pseudomonas sp. prevent gamma-actinorhodin biosynthesis
      by Streptomyces coelicolor A3(2).
AB  - Streptomyces are ubiquitous soil bacteria well known for their ability to produce
      a wide range of secondary metabolites including antibiotics. In their natural
      environments, they co-exist and interact with complex microbial communities and
      their natural products are assumed to play a major role in mediating these
      interactions. Reciprocally, their secondary metabolism can be influenced by the
      surrounding microbial communities. Little is known about these complex
      interactions and the underlying molecular mechanisms. During pairwise co-culture
      experiments, a fluorescent Pseudomonas, Pseudomonas fluorescens BBc6R8, was shown
      to prevent the production of the diffusible blue pigment antibiotic gamma
      actinorhodin by Streptomyces coelicolor A3(2) M145 without altering the
      biosynthesis of the intracellular actinorhodin. A mutant of the BBc6R8 strain
      defective in the production of gluconic acid from glucose and consequently unable
      to acidify the culture medium did not show any effect on the gamma-actinorhodin
      biosynthesis in contrast to the wild-type strain and the mutant complemented with
      the wild-type allele. In addition, when glucose was substituted by mannitol in
      the culture medium, P. fluorescens BBc6R8 was unable to acidify the medium and to
      prevent the biosynthesis of the antibiotic. All together, the results show that
      P. fluorescens BBc6R8 impairs the biosynthesis of the lactone form of
      actinorhodin in S. coelicolor by acidifying the medium through the production of
      gluconic acid. Other fluorescent Pseudomonas and the opportunistic pathogen
      Pseudomonas aeruginosa PAO1 also prevented the gamma-actinorhodin production in a
      similar way. We propose some hypotheses on the ecological significance of such
      interaction. 

PMID- 24906570
TI  - Two mechanisms for putrescine-dependent transcriptional expression of the
      putrescine aminotransferase gene, ygjG, in Escherichia coli.
AB  - In this study, on evaluating the physiological function and mechanism of
      putrescine, we found that putrescine supplementation (1 mM) increases
      transcription of the putrescine aminotransferase gene, ygjG. Putrescine-dependent
      expression was confirmed by measuring beta-galactosidase activity and with
      reverse transcription-polymerase chain reaction. To understand the role of
      putrescine in ygjG expression, we genetically characterized and found that a
      knockout mutation in an alternative sigma factor, rpoS, abolished putrescine
      dependent ygjG-lacZ expression. In the rpoS mutant, RpoS overexpression
      complemented the mutant phenotype. However, RpoS overexpression induced ygjG-lacZ
      expression with putrescine supplementation but not without supplementation. We
      also found that the loss of putrescine-dependent ygjG-lacZ expression induced by
      rpoS was completely restored under nitrogen-starvation conditions. The putrescine
      dependent expression of ygjG-lacZ under this condition was clearly dependent on
      another alternative sigma factor, rpoN, and its cognate activator ntrC. These
      results show that rpoS is required for putrescine-dependent ygjG-lacZ expression,
      but the effect of putrescine on this expression is not caused by simple
      modulation of RpoS synthesis. Putrescine-dependent expression of ygjG-lacZ was
      controlled by at least two sigma factors: rpoS under excess nitrogen conditions
      and rpoN under nitrogen-starvation conditions. These results suggest that
      putrescine plays an important role in the nitrogen regulation system. 

PMID- 24906571
TI  - [The impact of donor naive and memory T cell subsets on patient outcome following
      allogeneic stem cell transplantation: relationship between infused donor
      CD4+/CCR7+ T cell subsets and acute graft-versus-host disease].
AB  - In a previous prospective study on 62 patients who underwent an HLA-matched
      allogeneic stem cell transplantation, we have observed that proportion of donor
      derived CCR7(+)/CD4(+) T cells in the graft provided a predictive indicator of
      acute GVHD without interfering on chronic GVHD and relapse rate. Here we present
      our results on a confirmatory cohort of 137 consecutive patients. Indeed patients
      who received more than 76% of CCR7(+)/CD4(+) T cells in the graft developed more
      often acute GVHD be it of low or high grade than those who did not. Determination
      of the CCR7(+)/CCR7(neg) ratio of CD4(+) T cells in the graft provides a
      predictive indicator of acute GVHD and could help to define strategies of partial
      selective T cell depleted transplantation. 

PMID- 24906572
TI  - Recent advances in wrinkle-based dry adhesion.
AB  - Surface wrinkles driven by elastic instabilities have attracted significant
      interest in the field of materials science and engineering. They are simple and
      readily fabricated with various patterns of tunable size, morphology and surface
      topography from a wide range of material systems. Recently, they have been
      investigated as a new type of dry adhesives. In this review, after a brief
      introduction of different methods to prepare wrinkle surfaces, we focus on the
      investigation of dry adhesion mechanisms in different material systems. By
      exploiting wrinkle dimension, morphology, modulus, curvature, and different
      contacting surfaces (flat, hemispherical, spherical) and their complementarity,
      we show adhesion enhancement, reduction and selectivity. By comparing
      experimental results with theoretical predictions, we aim to provide a guideline
      to design and engineer wrinkle-based dry adhesives. Several examples of
      applications of engineered wrinkles are also demonstrated, including pick,
      release and transfer of nanoparticles and bulk materials, and gecko-like hybrid
      adhesives. The review is concluded with perspectives on the wrinkling technology
      for smart dry adhesives. 

PMID- 24906574
TI  - The Sarawak lupus cohort: clinical features and disease patterns of 633 SLE
      patients in a single tertiary centre from East Malaysia.
AB  - Systemic lupus erythematosus (SLE) has been well studied in West Malaysian
      populations but lacking in East Malaysian populations. The aim of this study was
      to examine the clinical features and disease patterns of patients with SLE in a
      multiethnic East Malaysian population in Sarawak. All SLE patients who were
      treated in Sarawak General Hospital were reviewed in a retrospective longitudinal
      study using a standard protocol from 1 January 2006 to 31 December 2013. There
      were a total of 633 patients in our study with the female to male ratio of 12:1.
      Our study patients were of multiethnic origins with predominant Chinese ethnic
      group. They had a mean age of 36.9 +/- 13.2 years and a mean duration of illness
      of 7.2 +/- 6.0 years. The main involvements were haematological (74.2 %), malar
      rash (64.0 %) and renal (58.6 %). Chinese patients were less likely to have
      discoid lupus, pleuritis and pericarditis, while Malay patients were more likely
      to have arthritis. Bidayuh patients were more likely to have oral ulcer.
      Secondary antiphospholipid syndrome was more common in Chinese. The majority of
      patients were in clinical remission with low SDI. There were 58 deaths (9.2 %)
      during 2006-2013 with the main causes of death being flare of disease and
      infection.

PMID- 24906573
TI  - Association of interferon regulatory factor 4 gene polymorphisms rs12203592 and
      rs872071 with skin cancer and haematological malignancies susceptibility: a meta
      analysis of 19 case-control studies.
AB  - BACKGROUND: Research has indicated that the rs12203592 and rs872071 interferon
      regulatory factor 4 (IRF4) gene polymorphisms correlate with the risk of cancer,
      especially skin cancer and haematological malignancies, but the results remain
      controversial. To understand better the effects of these two polymorphisms on
      skin cancer and haematological malignancies susceptibility, a cumulative meta
      analysis was performed. METHODS: We conducted a search using the PubMed and Web
      of Science databases for relevant case-control studies published before April
      2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs)
      were estimated using fixed- or random-effects models where appropriate.
      Heterogeneity test, publication bias test, and sensitivity analysis were also
      performed. RESULTS: In total, 11 articles comprised of 19 case-control studies
      were identified; five focused on the rs12203592 polymorphism with 7,992 cases and
      8,849 controls, and six were on the rs872071 polymorphism with 3108 cases and
      8300 controls. As for rs12203592, a significant correlation with overall skin
      cancer and haematological malignancies risk was found with the homozygote
      comparison model (OR=1.566, 95% CI 1.087-2.256) and recessive model (OR=1.526,
      95% CI 1.107-2.104). For rs872071, a significantly elevated haematological
      malignancies risk was observed in all genetic models (homozygote comparison:
      OR=1.805, 95% CI 1.402-2.323; heterozygote comparison: OR=1.427, 95% CI 1.203
      1.692; dominant: OR=1.556, 95% CI 1.281-1.891; recessive: OR=1.432, 95% CI 1.293
      1.587; additive: OR=1.349, 95% CI 1.201-1.515). Similarly, increased skin cancer
      and haematological malignancies risk was also identified after stratification of
      the SNP data by cancer type, ethnicity and source of controls for both
      polymorphisms. CONCLUSIONS: Our meta-analysis indicated that the rs12203592 and
      rs872071 IRF4 gene polymorphisms are associated with individual susceptibility to
      skin cancer and haematological malignancies. Moreover, the effect of the
      rs12203592 polymorphism on skin cancer risk was particularly prominent among
      Caucasians. Further functional research should be performed to validate the
      association.

PMID- 24906575
TI  - Anti-ribosomal-P antibodies in lupus nephritis, neuropsychiatric lupus, lupus
      hepatitis, and Chagas' disease: promising yet limited in clinical utility.
AB  - Anti-P antibodies have been associated with organ involvement in SLE, such as in
      autoimmune hepatitis, and have been suggested to be directly pathogenic.
      Neuropsychiatric lupus, lupoid hepatitis, autoimmune hepatitis, lupus nephritis,
      and Chagas' disease have been associated with the presence of anti-P antibody.
      This review seeks to look into the current literature on anti-P antibody and the
      association between SLE and non-SLE autoimmune connective tissue disorder. 

PMID- 24906576
TI  - Development of blastomere clones in the Ilyanassa embryo: transformation of the
      spiralian blastula into the larval body plan.
AB  - Spiralian embryogenesis is deeply conserved and seems to have been in place in
      the last common ancestor of the large assemblage of protostome phyla known as the
      Lophotrochozoa. While the blastula fate maps of several spiralian embryos have
      been determined, little is known about the events that link the early embryo and
      the larva. For all cells in the Ilyanassa blastula, we determined the clonal
      morphology at four time points between the blastula and veliger stages. We found
      that ectomesoderm comes mostly from 3a and 3b, but also from 2c and 2b. We also
      observed the ingression and early proliferation of 3a- and 3b-derived
      ectomesoderm. We found cells in the 2b clone that marked the anterior edge of the
      blastopore and later the mouth and cells in the 3c/3d clones that marked the
      posterior edges of these structures. This demonstrates directly that the mouth
      forms in the same location as the blastopore. In the development of the shell
      field, we observed dramatic cell migration events that invert the positions of
      the 2b and 2d clones that contribute to the shell. Using time-lapse imaging, we
      followed and described the cleavage pattern of the conserved endomesodermal blast
      cell, 4d, up to 4d + 45 h, when there were 52 cells in the clone. Our results
      show the growth and movement of clones derived from cells of the spiralian
      blastula as they transform into the trochophore-like and veliger stages. They
      have implications for the evolution of the shell in gastropods, the origins of
      mesoderm in spiralians, and the evolution of mouth formation in metazoans.

PMID- 24906577
TI  - Detection of Plasmodium falciparum and Plasmodium vivax subclinical infection in
      non-endemic region: implications for blood transfusion and malaria epidemiology.
AB  - BACKGROUND: In Brazil, malaria is endemic in the Amazon River basin and non
      endemic in the extra-Amazon region, which includes areas of Sao Paulo state. In
      this state, a number of autochthonous cases of malaria occur annually, and the
      prevalence of subclinical infection is unknown. Asymptomatic infections may
      remain undetected, maintaining transmission of the pathogen, including by blood
      transfusion. In these report it has been described subclinical Plasmodium
      infection in blood donors from a blood transfusion centre in Sao Paulo, Brazil.
      METHODS: In this cross-sectional study, representative samples of blood were
      obtained from 1,108 healthy blood donors at the Fundacao Pro-Sangue Hemocentro de
      Sao Paulo, the main blood transfusion centre in Sao Paulo. Malaria exposure was
      defined by the home region (exposed: forest region; non-exposed: non-forest
      region). Real-time PCR was used to detect Plasmodium falciparum and Plasmodium
      vivax. Subclinical malaria cases were geo-referenced. RESULTS: Eighty-four
      (7.41%) blood donors tested positive for Plasmodium; 57 of these were infected by
      P. falciparum, 25 by P. vivax, and 2 by both. The prevalence of P. falciparum and
      P. vivax was 5.14 and 2.26, respectively. The overall prevalence ratio (PR) was
      3.23 (95% confidence interval (CI) 2.03, 5.13); P. falciparum PR was 16.11 (95%
      CI 5.87, 44.21) and P. vivax PR was 0.47 (95% CI 0.2, 1.12). Plasmodium
      falciparum subclinical malaria infection in the Atlantic Forest domain was
      present in the mountain regions while P. vivax infection was observed in cities
      from forest-surrounded areas. CONCLUSIONS: The presence of Plasmodium in healthy
      blood donors from a region known as non-endemic, which is important in the
      context of transfusion biosafety, was described. Infected recipients may become
      asymptomatic carriers and a reservoir for parasites, maintaining their
      transmission. Furthermore, P. falciparum PR was positively associated with the
      forest environment, and P. vivax was associated with forest fragmentation.

PMID- 24906578
TI  - Far-red tracer analysis of traumatic cerebrovascular permeability.
AB  - BACKGROUND: Blood brain barrier (BBB) compromise is a key pathophysiological
      component of secondary traumatic brain injury characterized by edema and
      neuroinflammation in a previously immune-privileged environment. Current assays
      for BBB permeability are limited by working size, harsh extraction processes,
      suboptimal detection via absorbance, and wide excitation fluorescence spectra. In
      this study, we evaluate the feasibility of Alexa Fluor 680, a far-red dye
      bioconjugated to dextran, as an alternative assay to improve resolution and
      sensitivity. METHODS: Alexa Fluor was introduced intravenously on the day of
      sacrifice to three groups: sham, controlled cortical impact (CCI), and CCI
      treated with a cell based therapy known to reduce BBB permeability. The brains
      were sectioned coronally and imaged using an infrared laser scanner to generate
      intensity plot profiles as well as signal threshold images to distinguish regions
      with varying degrees of permeability. RESULTS: Linear plot profile analysis
      demonstrated greater signal intensity from CCI than treated rats at corresponding
      injury depths. Threshold analysis identified rims of signal at low + narrow
      threshold ranges. The integrated signals from a treatment group known to preserve
      the BBB were significantly less than the groups with CCI injury alone. There was
      no significant difference at high + wide signal intensity threshold ranges.
      CONCLUSIONS: Alexa Fluor 680 infrared photodetection and image analysis can aid
      in detecting differential degrees of BBB permeability after traumatic brain
      injury and maybe particularly useful in demonstrating BBB preservation of at-risk
      regions in response to therapeutic agents.

PMID- 24906579
TI  - Effectiveness of autogenic training in improving motor performances in
      Parkinson's disease.
AB  - BACKGROUND: Relaxation training can be an important adjunct in reducing symptoms
      associated with Parkinson's disease (PD). Autogenic Training (AT) is a simple,
      easily administered and inexpensive technique for retraining the mind and the
      body to be able to relax. AT uses visual imagery and body awareness to promote a
      state of deep relaxation. OBJECTIVE: To investigate whether AT when used as an
      adjunct to Physiotherapy (PT) improves motor performances in PD in comparison
      with a control group receiving PT alone. DESIGN: Randomized, controlled, single
      blinded trial. SETTING: Movement Disorder Clinic and Department of Physiotherapy,
      Sree Chithira Thirunal Institute of Medical Sciences and Technology in
      Trivandrum, Kerala, India. PARTICIPANTS: Patients with PD of grade 2 or 3 of
      Hoehn & Yahr (H&Y) scale (N = 66). INTERVENTIONS: AT group or control group. The
      techniques were administered by Physiotherapists trained in AT and consisted of
      40 sessions per patient over 8 weeks. MAIN OUTCOME MEASURE: Motor score subscale
      of Unified Parkinson's Disease Rating Scale (UPDRS) was used to measure the motor
      performances. The primary outcome measure was the difference in Motor score
      subscale of UPDRS scores between Week 1 (pretest score), Week 8 (posttest score),
      and follow-up at Week 12 after randomization. RESULTS: The simple main effects
      analysis showed that the AT group performed better than the control group in
      weeks 8 and 12 (P < .005). Patients in the AT and control groups reported a
      51.78% and 35.24% improvement, respectively, in their motor performances in Week
      8 compared with that in Week 1, which persisted, in the follow-up (Week 12) as
      30.82% in the AT group and 21.42% in the control group. CONCLUSIONS: This study
      provides evidence that AT when used as an adjunct to PT is more effective than PT
      alone in improving motor performances in PD patients.

PMID- 24906580
TI  - Dance for Parkinson's: a new framework for research on its physical, mental,
      emotional, and social benefits.
AB  - Parkinson's is a neurodegenerative disease commonly associated with symptoms such
      as tremor, rigidity, bradykinesia, freezing during gait, motor control deficits
      and instability. These physical symptoms can cause a myriad of psychological
      problems including depression, feelings of loneliness, and low self-esteem.
      Current research suggests pharmacological interventions do not sufficiently
      address all symptoms and thus alternative therapies have been deemed an important
      part of treatment for people with Parkinson's. Dance has shown to be a beneficial
      activity for this population. Upon reviewing recent dance for Parkinson's studies
      it is clear that there are developing trends with respect to overall approach.
      The tendency to place more emphasis on changes to clinical signs is creating a
      gap whereby research neglects to look at how dance is influencing a particular
      individual in all aspects of their life. There is a need for a framework that
      allows for and encourages the analysis of the dancing experience for people with
      Parkinson's on a variety of levels including physically, mentally, emotionally,
      and socially. With such a framework it would be possible to triangulate the
      information gathered to draw stronger conclusions that are more meaningful to the
      people with Parkinson's. This paper would like to propose the use of the World
      Health Organization's International Classification of Functioning, Disability,
      and Health as a possible framework for dance for Parkinson's research. 

PMID- 24906581
TI  - A comparison of the effects of hatha yoga and resistance exercise on mental
      health and well-being in sedentary adults: a pilot study.
AB  - OBJECTIVES: Physical activity has a positive effect on people's mental health and
      well-being. The aim of this study was to compare the effects of hatha yoga and
      resistance exercises on mental health and well-being in sedentary adults. DESIGN:
      Randomized controlled study. METHODS: Fifty-one participants aged mean (SD) 25.6
      (5.7) years were randomly divided into three groups: Hatha Yoga Group, Resistance
      Exercise Group and Control Group. The Hatha Yoga Group and Resistance Exercise
      Group participated in sessions three days per week for 7 weeks and the Control
      Group did not participate in any sessions. All the subjects were evaluated
      through the Rosenberg Self-Esteem Scale, Beck Depression Inventory, Body Cathexis
      Scale, Nottingham Health Profile and Visual Analog Scale for fatigue pre-and post
      session. RESULTS: Significant improvements were found in terms of all outcome
      measures in the Hatha Yoga Group and the resistance exercise group. No
      improvements were found in the Control Group. Hatha yoga more improved the
      dimensions fatigue, self-esteem, and quality of life, whilst resistance exercise
      training more improved body image. Hatha yoga and resistance exercise decreased
      depression symptoms at a similar level. CONCLUSION: The results indicated that
      hatha yoga and resistance exercise had positive effects on mental health and well
      being in sedentary adults. Hatha yoga and resistance exercise may affect
      different aspects of mental health and well-being.

PMID- 24906582
TI  - Yoga as an adjunct treatment for alcohol dependence: a pilot study.
AB  - OBJECTIVES: This pilot study explores the feasibility of yoga as part of a
      treatment program for alcohol dependence. DESIGN: Eighteen alcohol dependent
      patients were randomized to receive either treatment as usual or treatment as
      usual plus yoga. Assessments were taken at baseline and six month follow-up.
      SETTING: 'Riddargatan 1': an outpatient alcohol treatment clinic located in
      Stockholm, Sweden. INTERVENTIONS: Treatment as usual consisted of psychological
      and pharmacological interventions for alcohol dependence. The 10-week yoga
      intervention included a weekly group yoga session. Participants were encouraged
      to practice the yoga movements at home once per day. MAIN OUTCOME MEASURES:
      Alcohol consumption (timeline follow-back method, DSM-IV criteria for alcohol
      dependence, and the Short Alcohol Dependence Data questionnaire), affective
      symptoms (the Hospital Anxiety and Depression Scale), quality of life (Sheehan
      Disability Scale) and stress (the Perceived Stress Scale and saliva cortisol).
      RESULTS: Yoga was found to be a feasible and well accepted adjunct treatment for
      alcohol dependence. Alcohol consumption reduced more in the treatment as usual
      plus yoga group (from 6.32 to 3.36 drinks per day) compared to the treatment as
      usual only group (from 3.42 to 3.08 drinks per day). The difference was, however,
      not statistically significant (p = 0.17). CONCLUSIONS: Larger studies are needed
      to adequately assess the efficacy and long-term effectiveness of yoga as an
      adjunct treatment for alcohol dependence.

PMID- 24906583
TI  - Addendum: Safety Standards for Gua sha (press-stroking) and Ba guan (cupping).
AB  - Our previous article Safety Standards for Gua sha (press-stroking) and Baguan
      (cupping) discussed the risk of transfer of blood-borne pathogens with Gua sha
      and Ba guan, identified Gua sha and Ba guan 'instrument criticality' as semi
      critical and offered recommendations for safe practice based on hospital
      disinfection standards. Based on the article's feedback, we feel the need to
      clarify that Gua sha and Ba guan instruments, if intended for reuse, must undergo
      high level disinfection (HLD) or, in the case of 'wet-cupping', sterilization. We
      update our recommendations to be amenable to both private practice and education
      settings. 

PMID- 24906584
TI  - The effect of low-concentration atropine combined with auricular acupoint
      stimulation in myopia control.
AB  - OBJECTIVES: To compare the effect of myopia control between patients treated with
      low-concentration atropine eye drops combined with auricular acupoint stimulation
      and those treated with atropine alone. DESIGN AND SETTINGS: Single-blinded
      randomized controlled clinical trial in a regional teaching hospital.
      INTERVENTIONS: The patients received either topical 0.125% atropine nightly plus
      auricular acupoint stimulation (0.125A + ACU group) or topical 0.125% atropine
      alone nightly (0.125A group). MAIN OUTCOME MEASURES: The changes in spherical
      equivalent (SE), axial length (AL), anterior chamber depth (ACD), and intraocular
      pressure (IOP) per year were compared between the two groups. RESULTS: Seventy
      three of 110 total patients (66.4%) completed at least 6 months of follow-up.
      Patients in the 0.125A + ACU group had less myopic progression and AL elongation
      (-0.41 diopter and 0.24 mm/year) than those in the 0.125A group (-0.66 diopter
      and 0.32 mm/year) (mean follow-up 14.7 months, p < 0.0001 and p = 0.02,
      respectively). The ACD increased more in the 0.125A + ACU group than in the
      0.125A group (0.076 mm vs. 0.023 mm/year, p = 0.0004). IOP decreased more in the
      0.125A + ACU group than in the 0.125A group (-1.01 mmHg vs. -0.13 mmHg/year, p =
      0.007). A decrease of 1 mmHg of IOP correlated with a decrease of myopic
      progression of 0.021 diopter/year (p = 0.006). CONCLUSIONS: Patients treated with
      0.125% atropine eye drops plus auricular acupoint stimulation had less myopic
      progression, less axial length elongation, more anterior chamber deepening, and
      greater IOP reductions than those treated with 0.125% atropine alone. Auricular
      acupoint stimulation in combination with low-concentration topical atropine was
      beneficial for myopia control.

PMID- 24906585
TI  - Modulatory effects of aromatherapy massage intervention on electroencephalogram,
      psychological assessments, salivary cortisol and plasma brain-derived
      neurotrophic factor.
AB  - OBJECTIVES: Aromatherapy massage is commonly used for the stress management of
      healthy individuals, and also has been often employed as a therapeutic use for
      pain control and alleviating psychological distress, such as anxiety and
      depression, in oncological palliative care patients. However, the exact
      biological basis of aromatherapy massage is poorly understood. Therefore, we
      evaluated here the effects of aromatherapy massage interventions on multiple
      neurobiological indices such as quantitative psychological assessments,
      electroencephalogram (EEG) power spectrum pattern, salivary cortisol and plasma
      brain-derived neurotrophic factor (BDNF) levels. DESIGN: A control group without
      treatment (n = 12) and aromatherapy massage group (n = 13) were randomly
      recruited. They were all females whose children were diagnosed as attention
      deficit hyperactivity disorder and followed up in the Department of Psychiatry,
      Jeju National University Hospital. Participants were treated with aromatherapy
      massage for 40 min twice per week for 4 weeks (8 interventions). RESULTS: A 4
      week-aromatherapy massage program significantly improved all psychological
      assessment scores in the Stat-Trait Anxiety Index, Beck Depression Inventory and
      Short Form of Psychosocial Well-being Index. Interestingly, plasma BDNF levels
      were significantly increased after a 4 week-aromatherapy massage program. Alpha
      brain wave activities were significantly enhanced and delta wave activities were
      markedly reduced following the one-time aromatherapy massage treatment, as shown
      in the meditation and neurofeedback training. In addition, salivary cortisol
      levels were significantly reduced following the one-time aromatherapy massage
      treatment. CONCLUSIONS: These results suggest that aromatherapy massage could
      exert significant influences on multiple neurobiological indices such as EEG
      pattern, salivary cortisol and plasma BDNF levels as well as psychological
      assessments.

PMID- 24906586
TI  - Effectiveness of energy healing on Quality of Life: a pragmatic intervention
      trial in colorectal cancer patients.
AB  - PURPOSE: Our aim was to explore the effectiveness of energy healing, a commonly
      used complementary and alternative therapy, on well-being in cancer patients
      while assessing the possible influence on the results of participating in a
      randomized controlled trial. METHODS: 247 patients treated for colorectal cancer
      (response rate: 31.5%) were either (a) randomized to healing (RH) or control (RC)
      or (b) had self selected the healing (SH) or control condition (SC), and
      completed questionnaires assessing well-being (QoL, depressive symptoms, mood,
      and sleep quality), attitude toward complementary and alternative medicine (CAM),
      and faith/spirituality at baseline, 1 week, and 2 months post-intervention. They
      also indicated, at baseline, whether they considered QoL, depressive symptoms,
      mood, and sleep quality as important outcomes to them. RESULTS: Multilevel linear
      models revealed no overall effect of healing on QoL (p = 0.156), depressive
      symptoms (p = 0.063), mood (p = 0.079), or sleep quality (p = 0.346) in the
      intervention groups (RH, SH) compared with control (SC). Effects of healing on
      mood were only found for patients who had a positive attitude toward CAM and
      considered the outcome in question as important (SH: Regression coefficient: 
      8.78; SE: 2.64; CI: -13.96 to -3.61; p = 0.001, and RH: Regression coefficient 
      7.45; SE: 2.76; CI: -12.86 to -2.04; p = 0.007). CONCLUSION: Whereas it is
      generally assumed that CAMs such as healing have beneficial effects on well
      being, our results indicated no overall effectiveness of energy healing on QoL,
      depressive symptoms, mood, and sleep quality in colorectal cancer patients.
      Effectiveness of healing on well-being was, however, related to factors such as
      self-selection and a positive attitude toward the treatment.

PMID- 24906588
TI  - A novel model for exploring the correlation between patterns and prescriptions in
      clinical practice of traditional Chinese medicine for systemic lupus
      erythematosus.
AB  - OBJECTIVES: Traditional Chinese medicines in treating systemic lupus
      erythematosus are not uncommon. However, logic of pattern diagnosis and consensus
      on treating this disease is lacking. This study aimed to explore the correlation
      between the pattern diagnosis of and its corresponding prescription in systemic
      lupus erythematosus. DESIGN: Clinical data including patterns and prescriptions
      from the electronic medical records of lupus patients in a medical center were
      collected. Using a specific coding system (B-code) to encode the patterns and
      prescriptions provided a platform for data processing and statistics, and
      nonlinear canonical correlation analysis was employed to examine the correlation
      between them. RESULTS: In the 261 valid visits collected, a total of 46 patterns
      and 193 prescriptions were encoded into 57 B-codes. In our database, "Yin,
      Vacuity, Heat, and Dampness" were the most common B-codes (more than 90%) in both
      patterns and prescriptions. "Anemarrhena, Phellodendron, and Rehmannia Pill (Zhi
      Bai-Di-Huang-Wan)" and "Miltiorrhizae Radix (Dan-Shen)" were the most frequently
      used formula (52%) and herb (48%), respectively. Water-rheum, kidney, and stasis
      were among the three most effective variable sets for correlating the patterns
      and prescriptions. CONCLUSION: By using B-code with nonlinear canonical
      correlation analysis, the clinical dataset can be examined to shed light on the
      logic of pattern differentiation and principle of treatment for a specific
      disease.

PMID- 24906587
TI  - A randomized placebo controlled trial of an innovative herbal formula in the
      prevention of atherosclerosis in postmenopausal women with borderline
      hypercholesterolemia.
AB  - BACKGROUND: Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) (D&G) are
      two herbs frequently used for the treatment of angina and other cardiac symptoms
      in Chinese materia medica. Recent studies have demonstrated their cardio
      protective and anti-atherosclerosis effects. Earlier we have conducted two
      clinical trials in 2004 and 2007 which demonstrated such effects in extremely
      high risk patients. STUDY OBJECTIVE: The aim of the study was to demonstrate the
      safety and effectiveness of D&G in the prevention of atherosclerosis in
      postmenopausal women with early hypercholesterolemia. DESIGN: The study was
      designed as a randomized, double-blinded, placebo-controlled trial with a 12
      month treatment period. SUBJECT: A population based sample of 165 postmenopausal
      women aged 47-65 were included in the trial. Only women who experienced menopause
      for more than 12 months were recruited. INTERVENTIONS: The eligible subjects were
      randomized to take the D&G preparation (two capsules), or image-identical placebo
      capsules (two capsules) daily, in a double-blind and parallel fashion for 12
      month. MEASUREMENTS: The postmenopausal women with mild hypercholesterolemia
      (mean age 56.5 +/- 4.1 of treatment group and 56.0 +/- 3.8 years of placebo
      group) were randomized to the D&G group or placebo group for trial treatment.
      Carotid intima-media thickness (IMT) was used as the surrogate marker and was
      measured using high resolution ultrasound. Lipid profile was also tested.
      RESULTS: Baseline characteristics were comparable between the two groups. After
      12 months, there were no significant changes in the blood pressures and general
      biochemical profiles in both groups, however, there was a remarkable decrease in
      serum low density lipoprotein (LDL) cholesterol (-6.92%) and total cholesterol
      (TC) (-5.85%) in the D&G group compared with the placebo group (-3.21% and 
      3.42%) when compared with the baseline. The carotid intima-media thickness (IMT)
      decreased 1.52% from baseline in the D&G group (p < 0.004) but the decrease was
      only 1.13% in the placebo treatment group (p = 0.009) after 12 months treatment.
      Twelve adverse events were reported (six in placebo group and six in D&G group)
      but none of them was directly relevant to the study herbal preparation.
      CONCLUSIONS: Postmenopausal women with early hypercholesterolemia tolerated D&G
      well. D&G improved the carotid intima thickness, lowered LDL and total
      cholesterol. D&G therefore can be recommended for the prevention of
      atherosclerosis in postmenopausal women with hypercholesterolemia.

PMID- 24906589
TI  - Changes in the use of complementary and alternative medicine in Taiwan: a
      comparison study of 2007 and 2011.
AB  - OBJECTIVE: In this study, we explored the differences in the use of complementary
      and alternative medicine (CAM) based on data from 2007 and 2011 national surveys
      in Taiwan. RESEARCH DESIGN: Two cross-sectional, community-based epidemiological
      surveys were conducted in Taiwan. Participants 18 years and older were
      interviewed regarding their CAM use in the previous 12 months. Nationally
      representative random-household telephone surveys using a sampling method with a
      probability proportional to size were conducted in 2007 and 2011. The data were
      analysed to compare the results between surveys. RESULTS: We obtained a total of
      1260 and 2266 valid responses in 2007 and 2011, respectively. The use of at least
      one or more CAM therapies during the previous year decreased from 48.9% in 2007
      to 37.8% in 2011 (p < .001). In both surveys, the most common CAM therapies used
      were Chinese medicinal herbs followed by health supplement products and tuina. We
      observed the greatest relative increase in CAM use between 2007 and 2011 in
      health supplement products (12.8% vs. 16.0%) and massage (1.3% vs. 2.9%), whereas
      the largest relative decrease occurred for tuina (24.4-13.4%) and Chinese
      medicinal herbs (31.6-25.4%). CONCLUSION: Widespread CAM use reflects a more
      personal orientation towards maintaining health and selecting health care support
      services. Thus, a set of standards should be established for the safety and
      effectiveness of therapies, and consensus building is required to overcome the
      differences among practitioners from various backgrounds and traditions.

PMID- 24906590
TI  - A nationwide population-based study of traditional Chinese medicine usage in
      children in Taiwan.
AB  - OBJECTIVES: To characterize the application of traditional Chinese medicine (TCM)
      among pediatric patients. DESIGN AND SETTING: This study examined data sets from
      the National Health Insurance Research Database in Taiwan. Two cohorts, each with
      one million patients who were randomly sampled from the beneficiaries of the
      National Health Insurance Program from January 1 to December 31 in 2005 or 2010,
      were chosen for analysis. Children had at least one TCM outpatient clinical
      record were defined as TCM users, whereas children who had no TCM outpatient
      records were defined as non-TCM users. MAIN OUTCOME MEASURES: The demographic
      data, treatment modalities and the disease distributions of the pediatric TCM
      users were analyzed from two randomly sampled cohorts. RESULTS: Overall, 22% and
      22.5% of the children used TCM in 2005 and 2010, respectively. The utilization
      rate of TCM increased with age. Herbal remedies were the most commonly used
      therapeutic approach, followed by manipulative therapy and acupuncture. There was
      an increasing trend of using herbal remedies (increased from 65.6% to 74.4%) and
      acupuncture (increase from 7.5% to 11.4%), but there was a markedly decreased use
      of manipulative therapies from 25.6% to 12.3% from 2005 to 2010. There is an
      obvious increasing use of TCM due to diseases of the digestive system,
      skin/subcutaneous tissue and genitourinary system from 2005 to 2010. A further
      comparison of the prevalence rates between TCM and non-TCM visits indicated that
      allergic rhinitis, dyspepsia, injury and musculoskeletal diseases, as well as
      menstrual disorders, were the main diseases that children tended to visit TCM
      clinics in Taiwan. CONCLUSIONS: Our nationwide population-based study revealed
      the high prevalence and specific usage patterns of TCM in the pediatric
      population in Taiwan. The results of this study should provide valuable
      information for physicians, parents and the government concerning pediatric
      healthcare.

PMID- 24906591
TI  - Yoga for hypertension: a systematic review of randomized clinical trials.
AB  - OBJECTIVES: To critically evaluate the effectiveness of yoga as a treatment of
      hypertension. METHODS: Seventeen databases were searched from their inceptions to
      January 2014. Randomized clinical trials (RCTs) were included, if they evaluated
      yoga against any type of control in patients with any form of arterial
      hypertension. Risk of bias was estimated using the Cochrane criteria. Three
      independent reviewers performed the selection of studies, data extraction, and
      quality assessments. RESULTS: Seventeen trials met the inclusion criteria. Only
      two RCTs were of acceptable methodological quality. Eleven RCTs suggested that
      yoga leads to a significantly greater reduction in systolic blood pressure (SBP)
      compared to various forms of pharmacotherapy, breath awareness or reading, health
      education, no treatment (NT), or usual care (UC). Eight RCTs suggested that yoga
      leads to a significantly greater reduction in diastolic blood pressure (DBP) or
      night-time DBP compared to pharmacotherapy, NT, or UC. Five RCTs indicated that
      yoga had no effect on SBP compared to dietary modification (DIM), enhanced UC,
      passive relaxation (PR), or physical exercises (PE). Eight RCTs indicated that
      yoga had no effect on DBP compared to DIM, enhanced UC, pharmacotherapy, NT, PE,
      PR, or breath awareness or reading. One RCT did not report between-group
      comparisons. CONCLUSION: The evidence for the effectiveness of yoga as a
      treatment of hypertension is encouraging but inconclusive. Further, more rigorous
      trials seem warranted.

PMID- 24906592
TI  - Acupuncture and acupressure for pain management in labour and birth: a critical
      narrative review of current systematic review evidence.
AB  - BACKGROUND: Reviews of maternity services highlight the need for a reduction of
      medical interventions for women with low risk pregnancies and births to prevent
      the potential cascade of interventions and their associated risks. Complementary
      medicines (CM) such as acupuncture and acupressure have claimed to be effective
      in reducing interventions in labour; however, systematic reviews of evidence to
      date are conflicting. AIMS: To examine current evidence from systematic reviews
      on the topic of acupuncture and acupressure for pain management in labour and
      birth, and to evaluate the methodological and treatment frameworks applied to
      this evidence. METHODS: A search limited to systematic reviews of the MEDLINE,
      CINAHL, PUBMED, EMBASE and Cochrane databases was performed in December 2013
      using the keywords 'CAM', 'alternative medicine', 'complementary medicine',
      'complementary therapies', 'traditional medicine', 'Chinese Medicine',
      'Traditional Chinese Medicine', 'acupuncture', 'acupressure', cross-referenced
      with 'childbirth', 'birth', labo*r', and 'delivery'. The quality of the evidence
      is also evaluated in the context of study design. RESULTS: The RCTs included in
      these systematic reviews differed in terms of study designs, research questions,
      treatment protocols and outcome measures, and yielded some conflicting results.
      It may be inappropriate to include these together in a systematic review, or
      pooled analysis, of acupuncture for labour with an expectation of an overall
      conclusion for efficacy. Trials of acupuncture and acupressure in labour show
      promise, but further studies are required. CONCLUSION: The use of current
      systematic reviews of the evidence for acupuncture and acupressure for labour and
      birth may be misleading. Appropriate methods and outcome measures for
      investigation of acupuncture and acupressure treatment should more carefully
      reflect the research question being asked. The use of pragmatic trials designs
      with woman-centred outcomes may be appropriate for evaluating the effectiveness
      of these therapies.

PMID- 24906593
TI  - Chinese massage (Tuina) for the treatment of essential hypertension: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Chinese massage, named Tuina, is commonly used in China and
      potentially effective for essential hypertension (EH). However, there is no
      critically appraised evidence such as systematic reviews or meta-analyses on the
      effectiveness and safety of Tuina for EH. METHODS: The following electronic
      databases: Pubmed, the Cochrane library, CNKI, the Wan Fang Database and VIP were
      searched for published and unpublished randomized controlled trials (RCTs) of
      Tuina for EH up to 20th August 2013. RESULTS: Seven randomized trials involving
      479 patients were included. The results of meta-analysis showed superior effects
      of Tuina plus antihypertensive drugs compared to antihypertensive drugs alone,
      however, Tuina alone was not superior to antihypertensive drugs. The safety of
      Tuina for EH was still unclear because adverse effects were not assessed in most
      of the original trials. CONCLUSIONS: The findings from our review suggest that
      Tuina might be a beneficial adjuvant for patients with EH, although the results
      are of limited value due to the clinical heterogeneity and low methodological
      quality of the included studies. Future studies should adhere to high-quality
      RCTs with long follow-up for demonstrating the effectiveness of Tuina for
      inpatients with EH.

PMID- 24906594
TI  - Effectiveness and safety of Wuling capsule for post stroke depression: a
      systematic review.
AB  - OBJECTIVE: To review the effectiveness and safety of Wuling capsule for post
      stroke depression (PSD) systematically. METHODS: We searched electronic databases
      for randomized controlled trials (RCTs) that compared either Wuling capsule with
      placebo, no treatment or Wuling capsule plus conventional treatment with
      conventional treatment alone in adults with post stroke depression. Relevant
      resources were also retrieved. Two reviewers screened the citations, assessed the
      risk of bias and extracted data independently. RESULTS: A total of 16 studies
      involving 1378 patients were identified for this review. There were 3 trials
      comparing Wuling capsule with no treatment control and 13 trials comparing Wuling
      capsule plus conventional treatment (Deanxit, Fluoxetine, Sertraline, Paroxetine
      or Citalopram) with conventional treatment alone. Meta-analyses indicated Wuling
      capsule used alone or integrated with conventional treatment was effective for
      PSD in terms of HAMD (Hamilton depression scale) scores, response rate and with
      less adverse effects, of which, HAMD scores decreased significantly in favor of
      Wuling capsule from onset time to 1 week (SMD = 1.27, 95%CI: 0.71-1.83, P <
      0.00001), 2 weeks (SMD = 1.45, 95%CI: 0.57-2.33, P = 0.001), 4 weeks (SMD = 2.84,
      95%CI: 2.15-3.52, P < 0.00001), 6 weeks (SMD = 2.70, 95%CI: 2.15-3.24, P <
      0.00001), and 8 weeks (SMD = 4.53, 95%CI: 3.55-5.50, P < 0.00001) and overall
      effect (SMD = 2.40, 95%CI: 1.75-3.05, P < 0.00001) (SMD = standardized mean
      difference). CONCLUSION: Wuling capsule appeared to present certain
      antidepressant effect compared to no treatment control. With a combination of
      several Western medicines, Wuling capsule could be helpful in strengthening
      efficacy and reducing the incidence of adverse events as an alternative choice in
      the treatment of PSD. However, due to the limited number of included trials and
      relatively moderate methodological quality in the majority of studies, further
      large scale and rigorously designed trials are warranted to confirm the
      effectiveness and safety of Wuling capsule for post stroke depression.

PMID- 24906595
TI  - Chinese herbal medicine for cancer-related fatigue: a systematic review of
      randomized clinical trials.
AB  - OBJECTIVES: To assess the effectiveness and safety of Chinese herbal medicine for
      the treatment of cancer-related fatigue. METHODS: We systematically searched
      seven electronic databases and two trial registries for randomized clinical
      trials of Chinese herbal medicine for cancer-related fatigue. Two authors
      independently extracted data and assessed the methodological quality of the
      included trials using the Cochrane risk of bias tool. Data were synthesized using
      RevMan 5.2 software. RESULTS: A total of 10 trials involving 751 participants
      with cancer-related fatigue were identified and the methodological quality of the
      included trials was generally poor. Chinese herbal medicine used alone or in
      combination with chemotherapy or supportive care showed significant relief in
      cancer-related fatigue compared to placebo, chemotherapy or supportive care based
      on single trials. Chinese herbal medicine plus chemotherapy or supportive care
      was superior to chemotherapy or supportive care in improving quality of life.
      Data from one trial demonstrated Chinese herbal medicine exerted a greater
      beneficial effect on relieving anxiety but no difference in alleviating
      depression. Seven trials reported adverse events and no severe adverse effects
      were found in Chinese herbal medicine groups. CONCLUSIONS: The findings from
      limited number of trials suggest that Chinese herbal medicine seems to be
      effective and safe in the treatment of cancer-related fatigue. However, the
      current evidence is insufficient to draw a confirmative conclusion due to the
      poor methodological quality of included trials. Thus, conducting rigorously
      designed trials on potential Chinese herbal medicine is warranted.

PMID- 24906596
TI  - Quantiosomes as a multimodal nanocarrier for integrating bioimaging and
      Carboplatin delivery.
AB  - PURPOSE: Here we report the development of quantiosomes, niosomes formed from
      Span 60, cholesterol, and quantum dots (QDs), for achieving sensitive bioimaging
      and anticancer drug delivery. METHODS: The nanocarriers were further modified by
      incorporating soy phosphatidylcholine (SPC), polyethylene glycol (PEG), or
      cationic surfactant to display different efficiencies. Carboplatin was used as
      the model drug. The cellular uptake, cytotoxicity, and migration inhibition of
      quantiosomes for treating melanoma cells were described. Finally, intratumoral
      carboplatin accumulation and in-vivo bioimaging were examined. RESULTS: The
      average diameters of quantiosomes ranged between 151 and 173 nm, depending on the
      composition selected. Approximately 50% of the drug was entrapped in
      quantiosomes. Electron microscopy confirmed the bilayer structure of quantiosomes
      and the presence of QDs in the vesicular surface. The nanodispersions showed a
      significant internalization into cells, especially the cationic formulations.
      Quantiosomes increased cytotoxicity against melanoma by 3 ~ 4-fold as compared to
      free carboplatin. In-vivo intratumoral administration demonstrated an increased
      drug depot in melanoma from 6 to 10 ng/mg by SPC-loaded and PEGylated
      quantiosomes relative to aqueous control. In-vivo fluorescence imaging showed
      that quantiosomes reduced leakage of QDs from melanoma. A fluorescence signal
      confined in tumors could be sustained for at least 24 h. Quantiosomes also
      exhibited a sensitive and prolonged fluorescence in ovarian tumors. CONCLUSION:
      Niosomes containing QDs and carboplatin as a multifunctional nanosystems provide
      a non-expensive and efficient strategy to prolong drug retention and fluorescence
      signal in tumors.

PMID- 24906597
TI  - Pharmacokinetics and efficacy of the spleen tyrosine kinase inhibitor r406 after
      ocular delivery for retinoblastoma.
AB  - PURPOSE: Retinoblastoma is a childhood cancer of the retina. Clinical trials have
      shown that local delivery of broad spectrum chemotherapeutic agents is
      efficacious. Recent studies characterizing the genomic and epigenomic landscape
      of retinoblastoma identified spleen tyrosine kinase (SYK) as a promising
      candidate for targeted therapy. The purpose of this study was to conduct
      preclinical testing of the SYK antagonist R406 to evaluate it as a candidate for
      retinoblastoma treatment. METHODS: The efficacy of the SYK antagonist R406
      delivered locally in a human orthotopic xenograft mouse model of retinoblastoma
      was tested. Intraocular exposure of R406 was determined for various routes and
      formulations. RESULTS: There was no evidence of efficacy for subconjunctival.
      R406. Maximal vitreal concentration was 10-fold lower than the minimal
      concentration required to kill retinoblastoma cells in vitro. Dosage of R406
      subconjunctivally from emulsion or suspension formulations, direct intravitreal
      injection of the soluble prodrug of R406 (R788), and repeated topical
      administration of R406 all increased vitreal exposure, but failed to reach the
      exposure required for retinoblastoma cell death in culture. CONCLUSION: Taken
      together, these data suggest that R406 is not a viable clinical candidate for the
      treatment of retinoblastoma. This study highlights the importance of
      pharmacokinetic testing of molecular targeted retinoblastoma therapeutics.

PMID- 24906599
TI  - Duration and magnitude of vasopressor support predicts poor outcome after infant
      cardiac operations.
AB  - BACKGROUND: The vasoactive inotrope score (VIS) is a sum of the total vasopressor
      dose at a single point in time. Incorporating duration and magnitude of
      vasopressor requirements during the postcardiac surgical period could improve VIS
      sensitivity for predicting poor outcome. METHODS: This is a retrospective review
      of 244 infants (aged <=365 days) who underwent cardiopulmonary bypass during
      congenital cardiac operations from 2002 to 2011. The VIS was calculated hourly
      for the first 72 hours. Poor outcome was defined as prolonged mechanical
      ventilation (>=6 days) or intensive care length of stay (>=12 days). First, the
      association between the maximum VIS (maxVIS) in the first 48 postoperative hours
      and poor outcome was confirmed for our study population. Next, postoperative
      intervals and VIS values that were significantly associated with poor outcome
      were identified and incorporated into a formula, termed the VISindex, which was
      compared with the traditional maxVIS. RESULTS: The VISindex demonstrated improved
      sensitivity for predicting prolonged mechanical ventilation (VISindex: area under
      the curve [AUC], 0.85; 95% confidence interval [CI], 0.79 to 0.90; maxVIS: AUC,
      0.80; 95% CI, 0.75 to 0.86) and intensive care unit length of stay (VISindex:
      AUC, 0.84; 95% CI, 0.79 to 0.89; maxVIS: AUC, 0.77; 95% CI, 0.71 to 0.83) after
      cardiac operations in infants. CONCLUSIONS: Incorporating magnitude and duration
      of postoperative vasopressor support into the VIS improves its sensitivity for
      predicting poor outcome.

PMID- 24906598
TI  - Concentration dependent viscosity of monoclonal antibody solutions: explaining
      experimental behavior in terms of molecular properties.
AB  - PURPOSE: Early identification of monoclonal antibody candidates whose
      development, as high concentration (>=100 mg/mL) drug products, could prove
      challenging, due to high viscosity, can help define strategies for candidate
      engineering and selection. METHODS: Concentration dependent viscosities of 11
      proprietary mAbs were measured. Sequence and structural features of the variable
      (Fv) regions were analyzed to understand viscosity behavior of the mAbs. Coarse
      grained molecular simulations of two problematic mAbs were compared with that of
      a well behaved mAb. RESULTS: Net charge, xi-potential and pI of Fv regions were
      found to correlate with viscosities of highly concentrated antibody solutions.
      Negative net charges on the Fv regions of two mAbs with poor viscosity behaviors
      facilitate attractive self-associations, causing them to diffuse slower than a
      well-behaved mAb with positive net charge on its Fv region. An empirically
      derived equation that connects aggregation propensity and pI of the Fv region
      with high concentration viscosity of the whole mAb was developed. CONCLUSIONS: An
      Fv region-based qualitative screening profile was devised to flag mAb candidates
      whose development, as high concentration drug products, could prove challenging.
      This screen can facilitate developability risk assessment and mitigation
      strategies for antibody based therapeutics via rapid high throughput material
      free screening.

PMID- 24906600
TI  - Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy.
AB  - BACKGROUND: It is generally assumed that patient compliance with adjuvant
      chemotherapy is superior after video-assisted thoracoscopic surgery compared with
      open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for
      this assumption, however, is limited to single-institution, case-control studies.
      We used a complete national lung cancer registry. METHODS: For better comparison
      and reduction of selection bias, we analyzed only patients who underwent standard
      lobectomy for clinical stage 1 NSCLC and subsequently had unsuspected lymph node
      metastases discovered at final histopathology. A clinical oncologist, who was
      blinded to the surgical approach, reviewed all medical oncology charts for types
      of adjuvant chemotherapy, reasons for not initiating or stopping treatment,
      number of cycles delivered, and time interval from surgery to initial
      chemotherapy. RESULTS: During a 6-year period (2007 to 2012), 1,968 patients
      underwent standard lobectomy for clinical stage 1 NSCLC by video-assisted
      thoracoscopic surgery (n=990; 50.3%) or thoracotomy (n=978; 49.7%). Unsuspected
      nodal upstaging was later found in 341 patients (17.3%), and 313 were analyzed:
      189 patients (60.4%) received adjuvant chemotherapy and 121 (38.7%) completed all
      four cycles. Ordinal logistic regression revealed that chemotherapy compliance
      (none, partial, and full chemotherapy) was significantly reduced by the patient's
      age (p<0.001) and comorbidity index (p=0.003) but increased with N2 status
      (p=0.02). No significant difference between video-assisted thoracoscopic surgery
      and thoracotomy was seen regarding chemotherapy compliance (p=0.17), number of
      chemotherapy cycles (p=0.60), or time from surgery to chemotherapy (p = 0.41).
      CONCLUSIONS: Complete national data do not support the widespread assumption that
      adjuvant chemotherapy compliance is superior after thoracoscopic lobectomy for
      NSCLC. Instead, significant predictors of chemotherapy compliance are patient's
      age, comorbidity, and pathologic N status.

PMID- 24906601
TI  - The effect of modified Blalock-Taussig shunt size and coarctation severity on
      coronary perfusion after the Norwood operation.
AB  - BACKGROUND: The size of the modified Blalock-Taussig shunt and the additional
      presence of aortic coarctation can affect the hemodynamics of the Norwood
      physiology. Multiscale modeling was used to gather insight into the effects of
      these variables, in particular on coronary perfusion. METHODS: A model was
      reconstructed from cardiac magnetic resonance imaging data of a representative
      patient, and then simplified with computer-aided design software. Changes were
      systematically imposed to the semi-idealized three-dimensional model, resulting
      in a family of nine models (3-, 3.5-, and 4-mm shunt diameter; 0%, 60%, and 90%
      coarctation severity). Each model was coupled to a lumped parameter network
      representing the remainder of the circulation to run multiscale simulations.
      Simulations were repeated including the effect of preserved cerebral perfusion.
      RESULTS: The concomitant presence of a large shunt and tight coarctation was
      detrimental in terms of coronary perfusion (13.4% maximal reduction, 1.07 versus
      0.927 mL/s) and oxygen delivery (29% maximum reduction, 422 versus 300 mL.min(
      1).m(-2)). A variation in the ratio of pulmonary to systemic blood flow from 0.9
      to 1.6 also indicated a "stealing" phenomenon to the detriment of the coronary
      circulation. A difference could be further appreciated in the computational
      ventricular pressure-volume loops, with augmented systolic pressures and
      decreased stroke volumes for tighter coarctation. Accounting for constant
      cerebral perfusion did not produce substantially different results. CONCLUSIONS:
      Multiscale simulations performed in a parametric fashion revealed a reduction in
      coronary perfusion in the presence of a large modified Blalock-Taussig shunt and
      severe coarctation in Norwood patients.

PMID- 24906602
TI  - Multicenter international randomized comparison of objective and subjective
      outcomes between electronic and traditional chest drainage systems.
AB  - BACKGROUND: The aim of this study was to assess the impact of digital versus
      traditional drainage devices on chest tube removal and patient satisfaction.
      METHODS: A randomized trial of digital versus traditional devices after
      lobectomy/segmentectomy was conducted at 4 international centers (United Kingdom,
      Europe, Asia, United States). Patients were managed with overnight suction
      followed by gravity drainage. Chest tubes were removed when an air leak was not
      evident anymore and the drained fluid was less than 400 mL/d. RESULTS: The groups
      (digital, 191 patients; traditional, 190 patients) were well matched for baseline
      and surgical characteristics. There were 325 lobectomies/bilobectomies and 56
      segmentectomies, 308 of which were performed by video-assisted thoracic surgery
      (VATS). Patients randomized to digital systems had a significantly shorter air
      leak duration (1.0 versus 2.2 days; p=0.001), duration of chest tube placement
      (3.6 versus 4.7 days; p=0.0001), and postoperative length of stay (4.6 versus 5.6
      days; p<0.0001). Subjective end points revealed a perceived improved ability to
      arise from bed (p=0.008), system convenience for patients and personnel (p=0.02),
      and the potential for being comfortable when discharged home with the device
      (p=0.06). A mean difference of 2.6 days from air leak cessation to tube removal
      was observed, which was similar in the 2 groups (p=0.7). Multivariable regression
      analysis showed that duration of chest tube placement after air leak cessation
      was directly associated with the amount of fluid drained during the first 48
      hours (p=0.01) and the duration of air leak (p=0.008), independent of hospital
      location. CONCLUSIONS: Patients managed with digital drainage systems experienced
      a shorter duration of chest tube placement, shorter hospital stays, and higher
      satisfaction scores compared with those managed with traditional devices. (
      CLINICAL TRIAL REGISTRATION NUMBER: NCT01747889.).

PMID- 24906604
TI  - Quantitative comparisons of summary receiver operating characteristics (sROC)
      curves among conventional serological tumor biomarkers for predicting gastric
      cancer in Chinese population.
AB  - The objective of this study is to quantitatively analyze the predictive strength
      among the conventional serological tumor biomarkers for gastric cancer in Chinese
      population. Thirty-three hospital-based case-control studies were searched out
      through Chinese databases and PubMed during 1999-2009. Gastric cancer cases and
      healthy volunteers or benign gastric diseases controls were detected of any of
      serological CA724, CA242, CEA, CA199, CA125, or CA153. Areas under the curve
      (AUC) and optimal Q indexes of summary receiver operating characteristics (sROC)
      curves were quantitatively compared. The summary positive and negative likelihood
      ratios (sLR + and sLR-) were pooled. Totally, 2,390 gastric cancer cases and
      2,893 controls were analyzed. CA724 and CA242 both had the greatest AUCs (0.88),
      respectively, followed by the combination CA724 + CEA + CA199 (0.85), CA125
      (0.82), CEA (0.80), and CA199 (0.76), but all of them had no statistical
      significance to CA153 (negative control) by Z tests, possibly due to relatively
      great standard errors. The results of Q index analyses were similar to those of
      AUCs, that CA724 and CA242 had the optimal strength. The sLR + of CA724 (16.08,
      95 % confidence interval (CI) 7.86-32.86) or CA242 (11.03, 95 % CI 7.12-17.08)
      was strong to judge the gastric cancer status based on its positive result. The
      combination of CA724 + CEA + CA199 had the prior sLR- (0.33, 95 % CI 0.25-0.43)
      to the others. Serological CA724 or CA242 has predictive effect for screening
      gastric cancer and can be recommended into the screening program of population
      based or symptomatic cases. However, prospective epidemiological studies are
      required before confirmative conclusion.

PMID- 24906605
TI  - E-cadherin gene methylation in lung cancer.
AB  - E-cadherin, a tumor repressor gene, has been shown to play an important role in
      maintaining the polarity and structural integrity of epithelial and is closely
      associated with tumorigenesis, invasion, and metastasis. The current study aimed
      to investigate the effects of E-cadherin methylation on lung cancer (LC)
      quantitatively through a meta-analysis. We searched electronic databases to
      identify eligible studies from their inception through September 30, 2013. Pooled
      odds ratio (OR) with 95 % confidence interval (CI) was used to assess the
      relationship between E-cadherin gene methylation and LC risk. A hazard ratio (HR)
      with 95 % CI was used to assess the impact of E-cadherin gene methylation on
      overall survival (OS) of LC patients. Seventeen studies comprising 983 LC cases
      and 669 controls met the inclusion criteria. Summary results revealed that
      hypermethylation frequencies in LC tissues were significantly higher than those
      in normal control tissues (OR = 4.11, 95 % CI 2.78-6.07, P < 0.001). Subgroup
      analysis indicated that higher methylation frequencies were observed in Asian
      population. Interestingly, we found that hypermethylation of E-cadherin was
      associated with significantly better survival with HR of 0.47 (95 % CI 0.31
      0.71). This meta-analysis revealed that E-cadherin gene promoter methylation was
      associated with an increased risk of LC, especially in Asian population, and
      methylated E-cadherin predicted long survival in patients with LC. However,
      further studies with large numbers of patients will be needed to confirm the
      findings.

PMID- 24906606
TI  - Individuals having variant genotypes of cytochrome P450 2C19 are at increased
      risk of developing primary liver cancer in Han populations, without infection
      with the hepatitis virus.
AB  - Recently, many researchers have reported that the genetic polymorphisms of
      CYP2C19 may account for the interpatient variability of the clinical course in
      cancers including primary liver cancer (PLC). Besides the genetic polymorphisms
      of CYP2C19, hepatitis viruses (HV, including HAV, HBV, HCV, HDV, HEV, especially
      HBV and/or HCV) also account for the interpatient variability of the clinical
      course in PLC. This research covered the above two factors and divided the
      patients with PLC into two groups (one group with HBV infection and another
      without any HV infection) to find out whether the genetic polymorphisms of
      CYP2C19 have different effects in the progressing of PLC in different groups of
      patients. Eight hundred sixty-four cancer-free Han people (controls, named group
      1), 207 Han PLC patients with HBV infection (group 2), and 55 Han PLC patients
      without any HV infection (group 3) were involved in this study. A wild-type
      allele (CYP2C19*1) and two mutated alleles (CYP2C19*2 and CYP2C19*3) were
      identified. The frequencies of the mutant alleles and genotypes were then
      compared with each other. The frequencies of the homozygous and heterozygous
      variant genotypes (*2/*2, *2/*3, *3/*3) in group 3 (25.5 %) were significantly
      higher than those in other groups (11.9 % in group 1 and 13.5 % in group 2, P =
      0.014, 95 % confidence interval (CI)). The differences were statistically
      significant between group 1 and group 3 (P = 0.004, 95 % CI), but they were not
      statistically significant between group 1 and group 2 (P = 0.527, 95 % CI). Thus,
      we conclude that people which were not infected with HV but with the homozygous
      or heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) of CYP2C19 may have
      higher possibilities of getting PLC than people with other allelic genotypes
      (*1/*1, *1/*2, *1/*3) (odds ratio (OR) = 2.523, 95 % CI = 1.329 ~ 4.788).
      However, in patients with HBV infection, the genetic polymorphisms of CYP2C19 did
      not seem to be an important factor in the risk of developing PLC (OR = 1.156, 95
      % CI = 0.738 ~ 1.810).

PMID- 24906607
TI  - Incidence and predictors of atrial fibrillation and its impact on long-term
      survival in patients with supraventricular arrhythmias.
AB  - AIMS: To determine the incidence and predictors of atrial fibrillation (AF) and
      its impact on survival in patients with other forms of supraventricular
      arrhythmias (SVAs) including atrial flutter (AFL), atrial tachycardia (AT),
      atrioventricular reentrant (AVRT), and AV nodal reentrant tachycardia (AVNRT). We
      hypothesized that SVA may increase risk of AF and concomitant AF may influence
      long-term survival. METHODS AND RESULTS: All patients who underwent catheter
      ablation for SVA from 2000 to 2010 were included in this study. The patients were
      identified retrospectively and the vital status determined prospectively.
      Observed survival in the study cohort was compared with survival rates in the age
      and sex-matched general population. The study group included 1573 patients (mean
      age 50.5 +/- 18 years, 47% female) with AVNRT (38.5%), AFL (29.6%), AVRT (22.6%)
      and AT (9.3%). The patients were followed for a mean of 35 months (median 23
      months). Atrial fibrillation was documented in 424 patients (27%) with a higher
      incidence in males (35 vs. 18%). Atrial fibrillation was present in 19.6% of
      patients before the ablation and developed in 9.07% after ablation. Atrial
      fibrillation commonly occurred in patients with AFL (57.5%), AT (27.4%), AVRT
      (13.5%), and AVNRT (9.7%). Older age, prolonged PR interval, dilated left atrium,
      low left ventricular ejection fraction and presence of AFL were independent
      predictors for concomitant AF. Long-term survival was worse in the presence of
      AF. CONCLUSION: The incidence of AF is high in patients with other forms of SVA.
      The most common association is between AFL and AF. Long-term survival is
      decreased in those who have concomitant AF, although AF did not emerge as an
      independent predictor of mortality when adjusted for other covariates.

PMID- 24906608
TI  - Need for real-world data on management of the (potentially) failing lead.

PMID- 24906609
TI  - Physical counter-pressure manoeuvres in preventing syncopal recurrence in
      patients older than 40 years with recurrent neurally mediated syncope: a
      controlled study from the Third International Study on Syncope of Uncertain
      Etiology (ISSUE-3)?.
AB  - AIMS: Physical counter-pressure manoeuvres (PCM) are effective in young patients
      with vasovagal syncope and recognizable prodromal symptoms. The aim of this study
      was to investigate their effectiveness in patients >=40 years with severe
      neurally mediated syncope (NMS) enroled in the Third International Study on
      Syncope of Uncertain Etiology (ISSUE-3). METHODS AND RESULTS: In the ISSUE-3
      study, 63 out of 162 patients had a diagnosis of hypotensive NMS (Types 2, 3, and
      4A) documented by implantable loop recorder; of these, 40 were instructed to
      perform isometric leg and arm PCM therapy. Their mean age was 62 +/- 13 years;
      47% of patients had a history of some episodes without prodrome. A group of 45
      untreated patients acted as controls. The primary endpoint was the time to first
      syncope recurrence. During follow-up, syncope recurred in 15 PCM patients (37%)
      and in 24 control patients (53%) (P = 0.14). At 21 months, the modelled syncope
      recurrence rates were 42% [95% confidence interval (CI): 27-61] and 64% (95% CI:
      48-80), respectively (P = 0.27). CONCLUSION: In conclusion, many ISSUE-3 patients
      affected by hypotensive NMS have syncopal recurrence despite PCM. Older age and
      the absence of sufficiently long recognizable prodromal symptoms in the ISSUE-3
      population might have hampered the effectiveness of PC therapy.

PMID- 24906611
TI  - Obstacles hindering the mainstream practice of teledermatopathology.
AB  - BACKGROUND: Teledermatopathology has the potential to link underserved areas to
      experts across the country and assist in making quick diagnoses, which may
      improve health care costs and delivery. Despite these potential benefits,
      teledermatopathology is not used routinely for primary diagnosis in the United
      States. OBJECTIVE: To assess the current status of and address the potential for
      improving health care by the use of teledermatolopathology for primary diagnosis.
      METHODS: Current available literature and online resources were reviewed to
      address 3 major variables that hinder the widespread use of teledermatopathology:
      diagnostic accuracy, licensure requirements, and reimbursement. RESULTS: Recent
      studies show similar diagnostic accuracy for this technology compared to
      conventional microscopy. State-to-state variation and ambiguity in laws serve as
      the biggest hurdles to the widespread use of teledermatopathology. More states
      are recognizing the importance of the implementation of specific laws regarding
      telemedicine. More studies are required to evaluate the systems that offer
      specific telemedicine licenses, in addition to those that pay for telemedicine
      services specifically. LIMITATIONS: This study reviewed current legislation
      concerning teledermatopathology; these laws are subject to revision. CONCLUSION:
      Improving diagnostic accuracy and limiting variations in policy and reimbursement
      may encourage more pathologists to use teledermatopathology technology.

PMID- 24906610
TI  - Two decades of using the combination of tetracycline derivatives and niacinamide
      as steroid-sparing agents in the management of pemphigus: defining a niche for
      these low toxicity agents.
AB  - BACKGROUND: The twin goals of long-term disease control and minimizing toxicities
      related to immunosuppression necessitate efforts to find effective steroid
      sparing agents in the management of patients with autoimmune bullous diseases.
      Pemphigus especially requires a long view, because the disease can persist
      throughout a patient's lifetime, yet few clinical trial reports exist to guide
      the practitioner. OBJECTIVES: We review the response of pemphigus patients to
      tetracycline, doxycycline, or minocycline plus niacinamide (TCN/NAM) as steroid
      sparing therapy and to determine the effects of TCN/NAM on autoantibody levels
      during the long-term treatment of pemphigus. METHODS: This was a retrospective
      chart review in a private medical dermatology practice setting of all pemphigus
      patients treated between 1993 and 2013. Clinical responses to TCN/NAM therapy
      after initial high-dose steroid induction therapy and pemphigus antibody levels
      were recorded over the course of disease flares and treatment cycles along with
      any related side effects. Anti-desmoglein 1 and 3 titers were compared in a
      subset of patients over time, and a statistical analysis was performed to
      correlate the clinical response with antibody levels. RESULTS: Fifty-one
      pemphigus patients (43 with pemphigus vulgaris, 7 with pemphigus foliaceous, and
      1 with pemphigus erythematosus) received at least 3 months of TCN/NAM, and 16
      patients with pemphigus vulgaris had 1 set of pemphigus antibody titers
      correlating to a baseline/flare and clinical remission. TCN/NAM was associated
      with disease control in 43 of 51 patients, with a duration of response ranging
      from 1 to 13 years (mean, 3.14 +/- 2.97 years). Thirteen of 51 patients needed no
      additional treatment for complete disease control, while 33 of 51 needed
      intermittent topical clobetasol or short courses of oral steroids for long-term
      management. There were 5 nonresponders. Antidesmoglein titers trended lower in
      TCN/NAM responders, but only desmoglein 3 approached statistical significance
      (anti-desmoglein 1, P = .21; anti-desmoglein 3, P = .02). LIMITATIONS: This is a
      retrospective analysis from a single practice. A lack of serial autoantibody
      titers limited statistical analyses. CONCLUSION: TCN/NAM may be useful as a
      steroid-sparing therapy for pemphigus.

PMID- 24906612
TI  - The Cadaveric Skin Biopsy Project: description and student evaluation of an
      innovative approach to dermatology instruction in the preclerkship medical school
      curriculum.
AB  - BACKGROUND: Dermatology can develop creative ways of participating in the
      preclerkship medical school curriculum. OBJECTIVE: We sought to describe and
      report student survey results of a novel collaborative learning activity for
      medical students, directed by dermatology, histology, and gross anatomy faculty,
      which used cadavers to replicate the process of skin lesion biopsy and provided a
      realistic setting in which to learn normal-appearing and abnormal skin histology.
      METHODS: First-year medical students were surveyed regarding the impact of this
      activity on their understanding of skin histology and their appreciation of
      dermatology and dermatologic procedures. RESULTS: Students were appreciative of
      the opportunity to perform biopsies and discover the link between the clinical
      presentation of a lesion and its underlying histopathology. They were less
      impressed with the ability of the activity to improve their understanding of the
      characteristics of benign versus malignant lesions. LIMITATIONS: This is an early
      feasibility trial at 1 institution. CONCLUSIONS: This project represents one
      approach to introducing students to dermatology and dermatologic procedures and
      achieves institutional, Liaison Committee on Medical Education, and Association
      of American Medical Colleges educational goals. Overall, students highly valued
      the opportunities to practice clinical procedures and found it aided their
      understanding and appreciation of dermatology.

PMID- 24906613
TI  - Probiotics and prebiotics in dermatology.
AB  - The rapid increase in the medical use of probiotics and prebiotics in recent
      years has confirmed their excellent safety profile. As immune modulators, they
      have been used in inflammatory skin conditions, such as atopic dermatitis. We
      review the literature regarding the use of probiotics and prebiotics in
      dermatology. Probiotics and prebiotics appear to be effective in reducing the
      incidence of atopic dermatitis in infants, but their role in atopic dermatitis
      treatment is controversial. Their role in acne, wound healing, and
      photoprotection is promising, but larger trials are needed before a final
      recommendation can be made. 

PMID- 24906615
TI  - Efficacy and safety of felbamate in children with refractory epilepsy.
AB  - BACKGROUND: Despite the introduction of multiple new antiepileptic drugs in the
      past two decades, many patients with epilepsy continue to experience uncontrolled
      seizures or significant side effects. AIM: To present our experience with
      felbamate therapy in children with drug-resistant epilepsy. METHODS: We
      retrospectively reviewed the medical charts and video-EEG recordings of all
      patients receiving felbamate until May 2012. Efficacy was determined according to
      seizure frequency during the week prior to treatment initiation and the week
      after the maximal dosage of felbamate was reached. RESULTS: Fifty patients (34
      boys) aged 4 months to 17 years (mean--5.5 years) were identified. Nearly third
      of the patients had Lennox-Gastaut syndrome. Mean epilepsy duration was 3.4 years
      (range--1 month to 13 years). The mean number of previous antiepileptic drugs was
      7.5. The mean duration of follow-up was 1.1 years. Seizure frequency decreased by
      at least 50% in 29 (58%) patients. Side effects were reported in 22 (44%)
      patients, none of them included aplastic anemia or liver failure. In the
      responder group, the maximal dose of felbamate was lower and the patients were
      older compared to non-responders. CONCLUSIONS: Despite current recommendations,
      felbamate is initiated following multiple AEDs. Based on its efficacy and safety
      data, earlier initiation of felbamate is recommended in children with refractory
      epilepsy.

PMID- 24906614
TI  - Development of a novel noninvasive adhesive patch test for the evaluation of
      pigmented lesions of the skin.
AB  - BACKGROUND: The accurate clinical assessment of melanocytic neoplasms is a
      challenge for clinicians. Currently, obtaining a biopsy specimen and conducting a
      histologic examination is the standard of care. The incidence of melanoma in
      white populations is high, resulting in a large number of biopsy specimens.
      OBJECTIVE: The objective of this study is to develop a noninvasive genomic method
      using mRNA to classify pigmented skin lesions as either benign or malignant.
      METHODS: An adhesive patch method was used to obtain cells from the surface of
      melanocytic lesions. mRNA was extracted and a genomic signature was formulated in
      a training set of benign and malignant melanocytic neoplasms and subsequently
      tested in a validation set. RESULTS: A 2-gene signature assessing the expression
      levels of CMIP and LINC00518 was able to differentiate melanomas from nevi in an
      independent validation set of 42 melanomas and 22 nevi with a sensitivity of
      97.6% and specificity of 72.7%. LIMITATIONS: Larger and more diverse sets of
      melanomas and nevi are needed for additional validation of the molecular
      expression profiling in various subsets of melanocytic neoplasms. CONCLUSION: Our
      data suggest that mRNA molecular signatures can serve as a highly useful
      noninvasive method of differentiating melanoma from nevi and decrease the number
      of unnecessary biopsies.

PMID- 24906616
TI  - Cognitive modulation of pain and predictive coding. Comment on "Facing the
      experience of pain: a neuropsychological perspective" by Fabbro and Crescentini.

PMID- 24906617
TI  - Thrombus entrapment: the clue for coronary embolism.

PMID- 24906618
TI  - A papillary myxoma.

PMID- 24906619
TI  - Correlations between interpersonal and cognitive difficulties: relationship to
      suicidal ideation in military suicide attempters.
AB  - BACKGROUND: Understanding suicidal ideation may help develop more effective
      suicide screening and intervention programs. The interpersonal and the cognitive
      deficit theories seek to describe the factors leading to suicidal behavior. In
      the military setting it is common to find over- and under-reporting of suicidal
      ideation. This study sought to determine the relationship between these two
      models and determine to what degree their components can indirectly predict
      suicidal ideation. METHODS: Suicide attempters (n=32) were compared with non
      suicidal psychologically treated peers (n=38) and controls (n=33), matched for
      sex and age (mean 19.7years). Pearson's analysis was used to quantify the
      relationship between the variables from the two models and hierarchal regression
      analysis was used to determine the explanation of suicidal ideation variance by
      these variables. RESULTS: Suicide attempters have more difficulties in problem
      solving, negative emotion regulation and burdensomeness compared with their peers
      (P<.001). These variables are all closely correlated with each other and to
      suicide ideation (r>+/-0.5; P<.001). Prior suicide attempt, loneliness and
      burdensomeness together explain 65% (P<.001) of the variance in suicidal
      ideation. CONCLUSIONS: Suicidal ideation is strongly correlated with components
      of interpersonal and cognitive difficulties. In addition to assessing current
      suicidal ideation, clinicians should assess past suicide attempt, loneliness and
      burdensomeness.

PMID- 24906620
TI  - Apnea-hypopnea index use among intensive care patients: a case series.
AB  - INTRODUCTION: ApneaLinkTM (RESMED-Munich, Germany) is a simple and inexpensive
      device that determines the apnea-hypopnea index. The sensitivity and specificity
      of the apnea-hypopnea index are 100 and 87.5%, respectively. Our hypothesis can
      be used to create a treatment plan using the apnea-hypopnea index for intensive
      care unit patients. CASE PRESENTATION: This treatment plan has been created by
      determining the apnea-hypopnea index of eight Caucasian patients with a variety
      of diagnoses. Case 1 is that of a 70-year-old man diagnosed with rectum cancer
      and scheduled for elective surgery. Case 2 is that of a 65-year-old man diagnosed
      with rectum cancer and scheduled for elective surgery. Case 3 is that of a 78
      year-old woman diagnosed with chronic obstructive pulmonary disease-pneumonia.
      Case 4 is that of a 26-year-old man diagnosed with head trauma. Case 5 is that of
      an 80-year-old man diagnosed with cerebrovascular disease. Case 6 is that of a 79
      year-old man diagnosed with cerebrovascular disease. Case 7 is that of an 8-year
      old girl diagnosed with ventricular septal defect-epidural hemorragia. Case 8 is
      that of a 42-year-old man diagnosed with subarachnoid hemorrage. CONCLUSIONS: The
      apnea-hypopnea index can be informative regarding prognosis and outcomes, and
      helps to take precautions and develop new treatment strategies among critical
      patients in intensive care. The integration of developments in sleep medicine to
      intensive care unit practices means that we can be more informed about critical
      patients.

PMID- 24906621
TI  - Transient ablation of regulatory T cells improves antitumor immunity in colitis
      associated colon cancer.
AB  - Regulatory T cells (Treg) are supportive to cancer development in most tissues,
      but their role in colitis-associated colon cancer (CAC) remains unclear. In this
      study, we investigated the role of CD4(+)Foxp3(+) Treg in a mouse model of CAC
      and in patients with colon cancer. These Treg were increased strongly in number
      in a mouse model of CAC and in the peripheral blood of patients with colon
      cancer, exhibiting an activated phenotype as defined by elevated expression of
      GARP, CD103, CTLA-4, and IL10, along with an increased suppressive effect on the
      proliferation and Th1 cytokine expression of CD4(+)CD25(-) responder T cells ex
      vivo. Transient ablation of CD4(+)Foxp3(+) Treg during tumor development in the
      CAC model suppressed tumor outgrowth and distribution, accompanied by an
      increased number of CD8(+)IFNgamma/granzyme B-producing effector T cells.
      Conversely, inactivation of IL10 in Treg did not elevate the antitumor response
      but instead further boosted tumor development. Our results establish a tumor
      promoting function for Treg during CAC formation, but they also suggest that a
      selective, transient ablation of Treg can evoke antitumor responses, with
      implications for immunotherapeutic interventions in patients with CAC.

PMID- 24906622
TI  - Hippo coactivator YAP1 upregulates SOX9 and endows esophageal cancer cells with
      stem-like properties.
AB  - Cancer stem cells (CSC) are purported to initiate and maintain tumor growth.
      Deregulation of normal stem cell signaling may lead to the generation of CSCs;
      however, the molecular determinants of this process remain poorly understood.
      Here we show that the transcriptional coactivator YAP1 is a major determinant of
      CSC properties in nontransformed cells and in esophageal cancer cells by direct
      upregulation of SOX9. YAP1 regulates the transcription of SOX9 through a
      conserved TEAD binding site in the SOX9 promoter. Expression of exogenous YAP1 in
      vitro or inhibition of its upstream negative regulators in vivo results in
      elevated SOX9 expression accompanied by the acquisition of CSC properties.
      Conversely, shRNA-mediated knockdown of YAP1 or SOX9 in transformed cells
      attenuates CSC phenotypes in vitro and tumorigenicity in vivo. The small-molecule
      inhibitor of YAP1, verteporfin, significantly blocks CSC properties in cells with
      high YAP1 and a high proportion of ALDH1(+). Our findings identify YAP1-driven
      SOX9 expression as a critical event in the acquisition of CSC properties,
      suggesting that YAP1 inhibition may offer an effective means of therapeutically
      targeting the CSC population.

PMID- 24906623
TI  - An inducible hepatocellular carcinoma model for preclinical evaluation of
      antiangiogenic therapy in adult mice.
AB  - The limited availability of experimental tumor models that faithfully mimic the
      progression of human tumors and their response to therapy remains a major
      bottleneck to the clinical translation and application of novel therapeutic
      principles. To address this challenge in hepatocellular carcinoma (HCC), one of
      the deadliest and most common cancers in the world, we developed and validated an
      inducible model of hepatocarcinogenesis in adult mice. Tumorigenesis was
      triggered by intravenous adenoviral delivery of Cre recombinase in transgenic
      mice expressing the hepatocyte-specific albumin promoter, a loxP-flanked stop
      cassette, and the SV40 large T-antigen (iAST). Cre recombinase-mediated excision
      of the stop cassette led to a transient viral hepatitis and resulted in
      multinodular tumorigenesis within 5 to 8 weeks. Tumor nodules with histologic
      characteristics of human HCC established a functional vasculature by cooption,
      remodeling, and angiogenic expansion of the preexisting sinusoidal liver
      vasculature with increasing signs of vascular immaturity during tumor
      progression. Treatment of mice with sorafenib rapidly resulted in the induction
      of vascular regression, inhibition of tumor growth, and enhanced overall
      survival. Vascular regression was characterized by loss of endothelial cells
      leaving behind avascular type IV collagen-positive empty sleeves with remaining
      pericytes. Sorafenib treatment led to transcriptional changes of Igf1, Id1, and
      cMet over time, which may reflect the emergence of potential escape mechanisms.
      Taken together, our results established the iAST model of inducible
      hepatocarcinogenesis as a robust and versatile preclinical model to study HCC
      progression and validate novel therapies.

PMID- 24906624
TI  - A regulatory loop involving miR-22, Sp1, and c-Myc modulates CD147 expression in
      breast cancer invasion and metastasis.
AB  - Breast cancer is the most common cancer in women for which the metastatic process
      is still poorly understood. CD147 is upregulated in breast cancer and has been
      associated with tumor progression, but little is known about its regulatory
      mechanisms. In this study, we demonstrated that CD147 was overexpressed in breast
      cancer tissues and cell lines, and the high expression correlated with tumor
      invasion and metastasis. We also found that the transcription factors Sp1 and c
      Myc could bind to the CD147 promoter and enhance its expression. The CD147 mRNA
      has a 748-bp 3'-untranslated region (UTR) with many miRNA target sites,
      suggesting possible regulation by miRNAs. We discovered that miR-22 repressed
      CD147 expression by directly targeting the CD147 3'UTR. We also determined that
      miR-22 could indirectly participate in CD147 modulation by downregulating Sp1
      expression. miR-22 could form an autoregulatory loop with Sp1, which repressed
      miR-22 transcription by binding to the miR-22 promoter. Together with the c-Myc
      mediated inhibition of miR-22 expression, our investigation identified a miR
      22/Sp1/c-Myc network that regulates CD147 gene transcription. In addition, miR-22
      overexpression suppressed breast cancer cell invasion, metastasis, and
      proliferation by targeting CD147 in vitro and in vivo. Furthermore, we found that
      miR-22 was significantly downregulated in breast cancer tissues and that its
      expression was inversely correlated with the tumor-node-metastasis stage and
      lymphatic metastasis in patients. Our study provides the first evidence that an
      miR-22/Sp1/c-Myc network regulates CD147 upregulation in breast cancer and that
      miR-22 represses breast cancer invasive and metastatic capacities.

PMID- 24906625
TI  - A chamber of secrets. The neurology of the thalamus: lessons from acute stroke.

PMID- 24906626
TI  - Outcomes following definitive stereotactic body radiotherapy for patients with
      Child-Pugh B or C hepatocellular carcinoma.
AB  - PURPOSE: To report outcomes in patients with Child-Pugh B or C (CP B/C)
      hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy
      (SBRT). METHODS AND MATERIALS: A prospective study of SBRT was developed for
      patients with CP B7 or B8 unresectable HCC, <10 cm. Selected ineligible patients
      (e.g. CP>B8, >10 cm) treated off-study from 2004 to July 2012 were also reviewed.
      Patients were excluded if they were treated as a bridge-to-liver-transplant.
      RESULTS: 29 patients with CP B/C HCC were treated with SBRT (median dose 30 Gy in
      6 fractions) from 2004 to December 2012. The majority had CP B7 liver function
      (69%) and portal vein tumor thrombosis (76%). The median survival was 7.9 months
      (95% CI: 2.8-15.1). Survival was significantly better in patients with CP=B7 and
      AFP<=4491 ng/mL. Of 16 evaluable patients, 63% had a decline in CP score by >=2
      points at 3 months. CONCLUSION: SBRT is a treatment option for selected HCC
      patients with small HCCs and modestly impaired (CP B7) liver function.

PMID- 24906627
TI  - Percutaneous cryoablation of hepatic tumors adjacent to the gallbladder:
      assessment of safety and effectiveness.
AB  - PURPOSE: To assess safety and effectiveness of percutaneous image-guided
      cryoablation of hepatic tumors adjacent to the gallbladder. MATERIALS AND
      METHODS: Twenty-one cryoablation procedures were performed to treat 19 hepatic
      tumors (mean size, 2.7 cm; range, 1.0-5.0 cm) adjacent to the gallbladder in 17
      patients (11 male; mean age, 59.2 y; range, 40-82 y) under computed tomography (n
      = 15) or magnetic resonance imaging (n = 6) guidance in a retrospective study.
      All tumors (mean size, 2.67 cm; range, 1.0-5.0 cm) were within 1 cm (mean, 0.4
      cm) of the gallbladder; seven (33%) were contiguous with the gallbladder. Primary
      outcomes included complication rate and severity and postprocedure gallbladder
      imaging findings. Secondary outcomes included technical success and technique
      effectiveness at 6 months. RESULTS: Complications occurred in six of 21
      procedures (29%); one (5%) was severe. Ice balls extended into the gallbladder
      lumen in 20 of 21 procedures (95%); no gallbladder-related complications
      occurred. The most common gallbladder imaging finding was mild, asymptomatic
      focal wall thickening after nine of 21 procedures (42%), which resolved on follow
      up. Technical success was achieved in 19 of 21 sessions (90%). Six-month follow
      up was available for 16 tumors; of these, all but two (87%) had no imaging
      evidence of local tumor progression. CONCLUSIONS: Percutaneous cryoablation of
      hepatic tumors adjacent to the gallbladder can be performed safely and
      successfully. Although postprocedural gallbladder changes are common, they are
      self-limited and clinically inconsequential, even when the ice ball extends into
      the gallbladder lumen.

PMID- 24906628
TI  - A complement factor B mutation in a large kindred with atypical hemolytic uremic
      syndrome.
AB  - PURPOSE: Gain-of-function mutations in complement factor B (CFB) were recently
      identified in patients with atypical hemolytic uremic syndrome (aHUS), but are
      extremely rare. Our purpose is to describe a large kindred with aHUS associated
      with a CFB mutation and to further understand CFB-mutated aHUS patients. METHODS
      AND RESULTS: We report a large kindred in which 3 members had aHUS. This kindred
      revealed that 9 of 12 members, including 2 affected patients, had persistent
      activation of the alternative pathway with low complement component 3 and that
      those 9 members showed a CFB mutation (c.1050G > C, p.Lys350Asn) in exon 8. This
      missense mutation was heterozygous in 8 of them and homozygous in only one. From
      structural studies, this mutation is shown to be located in close proximity to
      the Mg2-binding site within a von Willebrand factor type A domain of CFB,
      resulting in a gain-of-function effect of CFB and predisposition to aHUS. At
      present, 2 of the 3 members with aHUS have maintained normal renal function for a
      long-term period. CONCLUSIONS: This kindred illustrates that a CFB mutation
      (c.1050G > C, p.Lys350Asn) can result in aHUS. In the future, phenotype-genotype
      correlations and outcome in CFB-mutated aHUS patients need to be further
      investigated by accumulation of a number of cases.

PMID- 24906629
TI  - Analytical approaches for the detection of emerging therapeutics and non-approved
      drugs in human doping controls.
AB  - The number and diversity of potentially performance-enhancing substances is
      continuously growing, fueled by new pharmaceutical developments but also by the
      inventiveness and, at the same time, unscrupulousness of black-market (designer)
      drug producers and providers. In terms of sports drug testing, this situation
      necessitates reactive as well as proactive research and expansion of the
      analytical armamentarium to ensure timely, adequate, and comprehensive doping
      controls. This review summarizes literature published over the past 5 years on
      new drug entities, discontinued therapeutics, and 'tailored' compounds classified
      as doping agents according to the regulations of the World Anti-Doping Agency,
      with particular attention to analytical strategies enabling their detection in
      human blood or urine. Among these compounds, low- and high-molecular mass
      substances of peptidic (e.g. modified insulin-like growth factor-1, TB-500,
      hematide/peginesatide, growth hormone releasing peptides, AOD-9604, etc.) and non
      peptidic (selective androgen receptor modulators, hypoxia-inducible factor
      stabilizers, siRNA, S-107 and ARM036/aladorian, etc.) as well as inorganic
      (cobalt) nature are considered and discussed in terms of specific requirements
      originating from physicochemical properties, concentration levels, metabolism,
      and their amenability for chromatographic-mass spectrometric or alternative
      detection methods.

PMID- 24906630
TI  - Spectroscopic limb monitoring in peripheral extracorporeal membrane oxygenation.
AB  - Limb-related complications are major contributors to extracorporeal membrane
      oxygenation-associated complications. Early detection of limb ischemia and or
      compartment syndrome is paramount to minimizing the adverse effects. With the
      absence of pulsatile flow, bedside Doppler examination of distal arterial
      waveforms is an impractical and an unreliable method of monitoring limb
      perfusion. We describe a new application of near-infrared spectroscopy monitoring
      of tissue oxygenation for the early detection of limb complications in
      extracorporeal membrane oxygenation. 

PMID- 24906631
TI  - An interesting case of straight back syndrome and review of the literature.
AB  - Straight back syndrome is characterized by loss of the normal upper thoracic
      kyphosis, leading to a reduced anteroposterior diameter and squashing of the
      heart. Most patients are asymptomatic; if symptomatic, chest pain and
      palpitations are most common. On examination, the abnormal clinical findings
      simulate organic heart disease that needs to be ruled out by echocardiography and
      cardiac catheterization. A lateral chest radiograph is diagnostic. This condition
      is commonly associated with mitral valve prolapse and bicuspid aortic valve. We
      describe an interesting case of straight back syndrome with all the classic and
      rarely reported clinical findings. 

PMID- 24906632
TI  - Single Heartstring aortotomy for multiple off-pump venous bypass grafts.
AB  - Off-pump coronary bypass grafting may decrease the rate of stroke, due to minimal
      aortic manipulation. For venous grafts, clampless hemostasis when performing the
      proximal anastomosis can be achieved using the Heartstring device. We describe a
      technique using a single device to suture two veins to one aortotomy. This
      technique requires less space and could be advantageous in very short, small, and
      calcified aortas. In to our experience, this technique is rapid, simple, easy to
      reproduce, and cost-saving. 

PMID- 24906633
TI  - Scoring docking conformations using predicted protein interfaces.
AB  - BACKGROUND: Since proteins function by interacting with other molecules, analysis
      of protein-protein interactions is essential for comprehending biological
      processes. Whereas understanding of atomic interactions within a complex is
      especially useful for drug design, limitations of experimental techniques have
      restricted their practical use. Despite progress in docking predictions, there is
      still room for improvement. In this study, we contribute to this topic by
      proposing T-PioDock, a framework for detection of a native-like docked complex 3D
      structure. T-PioDock supports the identification of near-native conformations
      from 3D models that docking software produced by scoring those models using
      binding interfaces predicted by the interface predictor, Template based Protein
      Interface Prediction (T-PIP). RESULTS: First, exhaustive evaluation of interface
      predictors demonstrates that T-PIP, whose predictions are customised to target
      complexity, is a state-of-the-art method. Second, comparative study between T
      PioDock and other state-of-the-art scoring methods establishes T-PioDock as the
      best performing approach. Moreover, there is good correlation between T-PioDock
      performance and quality of docking models, which suggests that progress in
      docking will lead to even better results at recognising near-native
      conformations. CONCLUSION: Accurate identification of near-native conformations
      remains a challenging task. Although availability of 3D complexes will benefit
      from template-based methods such as T-PioDock, we have identified specific
      limitations which need to be addressed. First, docking software are still not
      able to produce native like models for every target. Second, current interface
      predictors do not explicitly consider pairwise residue interactions between
      proteins and their interacting partners which leaves ambiguity when assessing
      quality of complex conformations.

PMID- 24906634
TI  - Prevalence and correlates of complementary and alternative medicine use among
      diabetic patients in Beirut, Lebanon: a cross-sectional study.
AB  - BACKGROUND: Patients with Type 2 Diabetes Mellitus (T2DM) are increasingly using
      complementary and alternative medicine (CAM) therapies due to difficulty in
      adhering to the therapeutic regimens and lifestyle changes necessary for disease
      management. Little is known about the prevalence and mode of CAM use among
      patients with T2DM in Lebanon. OBJECTIVE: To assess the prevalence and modes of
      CAM use among patients with T2DM residing in Beirut, Lebanon. METHODS: A cross
      sectional survey of T2DM patients was conducted on patients recruited from two
      major referral centers in Beirut--a public hospital and a private academic
      medical center. In a face-to-face interview, participants completed a
      questionnaire comprised of three sections: socio-demographic, diabetes
      characteristics and types and modes of CAM use. Descriptive statistics,
      univariate and multivariate logistic regression analyses were utilized to assess
      the prevalence and correlates of CAM use, as well as whether the use was
      complementary or alternative to mainstream medicine. The main outcome in this
      study, CAM use, was defined as using CAM at least once since diagnosis with T2DM.
      RESULTS: A total of 333 T2DM patients completed the survey (response rate:
      94.6%). Prevalence of CAM use since diagnosis with the disease was 38%. After
      adjustment, CAM use was significantly associated with a "married" status, a
      longer duration of T2DM, the presence of disease complications, and a positive
      family history of the disease. Folk foods and herbs were the most commonly used
      CAM followed by natural health products. One in five patients used CAM as
      alternative to conventional treatment. Only 7% of CAM users disclosed the CAM use
      to their treating physician. Health care practitioners were the least cited (7%)
      as influencing the choice of CAM among users. CONCLUSION: The use of CAM
      therapies among T2DM patients in Lebanon is prevalent. Decision makers and care
      providers must fully understand the potential risks and benefits of CAM therapies
      to appropriately advise their patients. Attention must be dedicated to educating
      T2DM patients on the importance of disclosing CAM use to their physicians
      especially patients with a family history of diabetes, and those who have had the
      disease for a long time.

PMID- 24906635
TI  - Adolescents' physical activity at recess and actions to promote a physically
      active school day in four Finnish schools.
AB  - The national Finnish Schools on the Move programme support schools with their
      individual plans to promote school-based physical activity (PA). We examined the
      changes in adolescents' recess and overall PA in four lower secondary schools and
      described the school actions to promote students' PA and the local contact
      persons' perceptions of the effects. Recess and overall PA were assessed four
      times by anonymous questionnaires from students in grades 7-9 (n = 789) in 2010
      12, and local contact persons (n = 7) provided information on school actions with
      diaries, interviews and surveys. Student data were analysed with descriptive
      statistics and chi-square tests, and school actions data were analysed with
      quantitative content analysis. The proportion of students who participated in
      physical activities at recess at least sometimes increased from 30% to 49% in
      physically active play and from 33% to 42% in ball games, mostly due to
      improvements in males' participation. Females' participation in recess activities
      increased in two schools with gender-specific physical activities or facilities.
      Overall PA levels declined slightly. Organized recess activities, student recess
      activators and equipment provision and sports facilities development were
      considered to have affected students' PA positively. Solutions for getting
      females more physically active in the school setting are needed. 

PMID- 24906636
TI  - Aicardi-Goutieres syndrome harbours abundant systemic and brain-reactive
      autoantibodies.
AB  - OBJECTIVES: Aicardi-Goutieres syndrome (AGS) is an autoimmune disorder that
      shares similarities with systemic lupus erythematous. AGS inflammatory responses
      specially target the cerebral white matter. However, it remains uncertain why the
      brain is the most affected organ, and little is known about the presence of
      autoantibodies in AGS. Here, we aim to profile specific autoantibodies in AGS and
      to determine whether these autoantibodies target cerebral epitopes. METHODS:
      Using a multiplex microarray, we assessed the spectrum of serum autoantibodies in
      56 genetically confirmed patients with AGS. We investigated the presence of
      immunoglobulins in AGS brain specimens using immunohistochemistry and studied the
      reactivity of sera against brain epitopes with proteomics. RESULTS: Serum from
      patients exhibited high levels of IgGs against nuclear antigens (gP210, Nup62,
      PCNA, Ro/SSA, Sm/RNP complex, SS-A/SS-B), components of the basement membrane
      (entactin, laminin), fibrinogen IV and gliadin. Upon testing whether antibodies
      in AGS could be found in the central nervous system, IgGs were identified to
      target in vivo endothelial cells in vivo and astrocytes in brain sections of
      deceased patients with AGS. Using a proteomics approach, we were able to confirm
      that IgGs in serum samples from AGS patients bind epitopes present in the
      cerebral white matter. CONCLUSIONS: Patients with AGS produce a broad spectrum of
      autoantibodies unique from other autoimmune diseases. Some of these
      autoantibodies target endothelial cells and astrocytes in the brain of the
      affected patients, perhaps explaining the prominence of neurological disease in
      the AGS phenotype.

PMID- 24906638
TI  - Rheumatoid arthritis: an antigenic chameleon.

PMID- 24906637
TI  - A 24-month open-label study of canakinumab in neonatal-onset multisystem
      inflammatory disease.
AB  - OBJECTIVE: To study efficacy and safety of escalating doses of canakinumab, a
      fully human anti-IL-1beta monoclonal antibody in the severe cryopyrin-associated
      periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID).
      METHODS: 6 patients were enrolled in this 24-month, open-label phase I/II study.
      All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was
      150 mg (or 2 mg/kg in patients <=40 kg) or 300 mg (or 4 mg/kg) with escalation up
      to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patient
      reported clinical components and measures of systemic inflammation and CNS
      inflammation. Hearing, vision and safety were assessed. Primary endpoint was full
      remission at month 6. RESULTS: All patients flared after anakinra withdrawal, and
      symptoms and serum inflammatory markers improved with canakinumab. All patients
      required dose escalation to the maximum dose. At month 6, none had full
      remission, although 4/6 achieved inflammatory remission, based on disease
      activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6
      due to persistent CNS leucocytosis. At the last study visit, 5/6 patients
      achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual
      acuity and field were stable in all patients, progressive hearing loss occurred
      in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a
      methicillin-resistant Staphylococcus aureus infection) occurred. CONCLUSIONS:
      Canakinumab at the studied doses improves symptoms and serum inflammatory
      features of NOMID, although low-grade CNS leukocytosis in four patients and
      headaches in one additional patient persisted. Whether further dose
      intensifications are beneficial in these cases remains to be assessed.
      CLINICALTRIALSGOV IDENTIFIER: NCT00770601.

PMID- 24906639
TI  - Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on
      susceptibility and subphenotypes of systemic lupus erythematosus and Sjogren's
      syndrome.
AB  - BACKGROUND: Recently, our research group identified the non-deleted (functional)
      leucocyte immunoglobulin-like receptor A3 (LILRA3) as a new genetic risk for
      rheumatoid arthritis. OBJECTIVES: To further investigate whether the functional
      LILRA3 is a new susceptibility factor for other autoimmune diseases-for example,
      systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS). METHODS:
      The LILRA3 deletion polymorphism and its tagging single nucleotide polymorphism
      rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and
      2169 healthy controls. Association analyses were performed in whole dataset or
      clinical/serological subsets. The impact of LILRA3 on SLE activity and LILRA3
      expression was evaluated. RESULTS: The functional LILRA3 conferred high
      susceptibility to both SLE (p=3.51*10(-7), OR=2.03) and pSS (p=1.40*10(-3),
      OR=2.32). It was associated with almost all the clinical/serological features in
      SLE, especially with leucopenia (p=4.09*10(-7), OR=2.19) and thrombocytopenia
      (p=1.68*10(-5), OR=1.70). In pSS, functional LILRA3 was specifically associated
      with leucopenia (p=4.39*10(-4), OR=3.25), anti-Ro/SSA-positive subphenotypes
      (p=4.54*10(-3), OR=2.34) and anti-La/SSB-positive subphenotypes (p=0.012,
      OR=2.49). Functional LILRA3 conferred higher disease activity in patients with
      SLE (p=0.044) and higher LILRA3 expression in both SLE (p=5.57*10(-8)) and pSS
      (p=1.49*10(-7)) than in controls. CONCLUSIONS: Functional LILRA3 is a new
      susceptibility factor for SLE and pSS. It highly predisposes to certain
      phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer
      increased disease activity in SLE and a higher risk of leucopenia and
      autoantibody-positive subphenotypes in pSS.

PMID- 24906640
TI  - Interplay of interlocus gene conversion and crossover in segmental duplications
      under a neutral scenario.
AB  - Interlocus gene conversion is a major evolutionary force that drives the
      concerted evolution of duplicated genomic regions. Theoretical models
      successfully have addressed the effects of interlocus gene conversion and the
      importance of crossover in the evolutionary fate of gene families and
      duplications but have not considered complex recombination scenarios, such as the
      presence of hotspots. To study the interplay between interlocus gene conversion
      and crossover, we have developed a forward-time simulator that allows the
      exploration of a wide range of interlocus gene conversion rates under different
      crossover models. Using it, we have analyzed patterns of nucleotide variation and
      linkage disequilibrium within and between duplicate regions, focusing on a
      neutral scenario with constant population size and validating our results with
      the existing theoretical models. We show that the interaction of gene conversion
      and crossover is nontrivial and that the location of crossover junctions is a
      fundamental determinant of levels of variation and linkage disequilibrium in
      duplicated regions. We also show that if crossover activity between duplications
      is strong enough, recurrent interlocus gene conversion events can break linkage
      disequilibrium within duplicates. Given the complex nature of interlocus gene
      conversion and crossover, we provide a framework to explore their interplay to
      help increase knowledge on molecular evolution within segmental duplications
      under more complex scenarios, such as demographic changes or natural selection. 

PMID- 24906642
TI  - Downregulation of miR-21 increases cisplatin sensitivity of non-small-cell lung
      cancer.
AB  - Recent studies have shown that plasma miR-21 is a biomarker of chemotherapeutic
      response in lung cancer, but the influence of miR-21 on the sensitivity of non
      small-cell lung cancer (NSCLC) to cisplatin (DDP) has not been confirmed. The aim
      of this study was to evaluate the role of miR-21 in NSCLC sensitivity to DDP in
      vitro and in vivo. Real-time quantitative PCR was used to detect miR-21
      expression in lung cancer cell lines. Synthesized locked nucleic acid (LNA) anti
      miR-21 was transiently transfected into A549 cells and pre-miR-21 was transfected
      into SK-MES-1 cells. We also investigated the effects of miR-21 downregulation
      and upregulation on growth and colony formation in DDP-treated cells. Finally,
      the effect of miR-21 downregulation on in vivo sensitivity of A549 cells to DDP
      was determined in BALB/c nude mice. miR-21 expression was significantly higher in
      A549 than in other lung cancer cell lines. LNA-based knockdown of miR-21
      significantly inhibited growth and induced death in A549 cells, possibly via
      apoptotic signaling. Pre-miR-21 significantly promoted growth and inhibited death
      in SK-MES-1 cells. Moreover, ectopic suppression of miR-21 sensitized A549 cells
      to DDP in vivo. Our findings demonstrate that miR-21 suppression enhances the
      sensitivity of lung cancer cells to DDP in vitro and in vivo.

PMID- 24906641
TI  - Measures of viral load using Abbott RealTime HIV-1 Assay on venous and
      fingerstick dried blood spots from provider-collected specimens in Malawian
      District Hospitals.
AB  - BACKGROUND: Viral suppression is a key indicator of antiretroviral therapy (ART)
      response among HIV-infected patients. Dried blood spots (DBS) are an appealing
      alternative to conventional plasma-based virologic testing, improving access to
      monitoring in resource-limited settings. However, validity of DBS obtained from
      fingerstick in field settings remains unknown. OBJECTIVES: Investigate
      feasibility and accuracy of DBS vs plasma collected by healthcare workers in real
      world settings of remote hospitals in Malawi. Compare venous DBS to fingerstick
      DBS for identifying treatment failure. STUDY DESIGN: We recruited patients from
      ART clinics at two district hospitals in Malawi, collecting plasma, venous DBS
      (vDBS), and fingerstick DBS (fsDBS) cards for the first 149 patients, and vDBS
      and fsDBS only for the subsequent 398 patients. Specimens were tested using
      Abbott RealTime HIV-1 Assay (lower detection limit 40 copies/ml (plasma) and 550
      copies/ml (DBS)). RESULTS: 21/149 (14.1%) had detectable viremia (>1.6 log
      copies/ml), 13 of which were detectable for plasma, vDBS, and fsDBS. Linear
      regression demonstrated high correlation for plasma vs. DBS (vDBS: beta=1.19,
      R(2)=0.93 (p<0.0001); fsDBS beta=1.20, R(2)=0.90 (p<0.0001)) and vDBS vs. fsDBS
      (beta=0.88, R(2)=0.73, (p<0.0001)). Mean difference between plasma and vDBS was
      1.1 log copies/ml [SD: 0.27] and plasma and fsDBS 1.1 log copies/ml [SD: 0.31].
      At 5000 copies/ml, sensitivity was 100%, and specificity was 98.6% and 97.8% for
      vDBS and fsDBS, respectively, compared to plasma. CONCLUSIONS: DBS from
      venipuncture and fingerstick perform well at the failure threshold of 5000
      copies/ml. Fingerstick specimen source may improve access to virologic treatment
      monitoring in resource-limited settings given task-shifting in high-volume, low
      resource facilities.

PMID- 24906643
TI  - LRRC26 is a functional BK channel auxiliary gamma subunit in arterial smooth
      muscle cells.
AB  - RATIONALE: Smooth muscle cell (myocyte) large-conductance calcium (Ca)(2+)
      activated potassium (BK) channels are functionally significant modulators of
      arterial contractility. Arterial myocytes express both pore-forming BKalpha and
      auxiliary beta1 subunits, which increase channel Ca(2+) sensitivity. Recently,
      several leucine-rich repeat containing (LRRC) proteins have been identified as
      auxiliary gamma subunits that elevate the voltage sensitivity of recombinant and
      prostate adenocarcinoma BK channels. LRRC expression and physiological functions
      in native cell types are unclear. OBJECTIVE: Investigate the expression and
      physiological functions of leucine-rich repeat containing protein 26 (LRRC26) in
      arterial myocytes. METHODS AND RESULTS: Reverse transcription polymerase chain
      reaction and Western blotting detected LRRC26 mRNA and protein in cerebral artery
      myocytes. Biotinylation, immunofluorescence resonance energy transfer microscopy,
      and coimmunoprecipitation indicated that LRRC26 was located in close spatial
      proximity to, and associated with, plasma membrane BKalpha subunits. LRRC26
      knockdown (RNAi) reduced total and surface LRRC26, but did not alter BKalpha or
      beta1, proteins in arteries. LRRC26 knockdown did not alter Ca(2+) sparks but
      reduced BK channel voltage sensitivity, which decreased channel apparent Ca(2+)
      sensitivity and transient BK current frequency and amplitude in myocytes. LRRC26
      knockdown also increased myogenic tone over a range (40-100 mm Hg) of
      intravascular pressures, and reduced vasoconstriction to iberiotoxin and
      vasodilation to NS1619, BK channel inhibitors and activators, respectively. In
      contrast, LRRC26 knockdown did not alter depolarization (60 mmol/L K(+))-induced
      vasoconstriction. CONCLUSIONS: LRRC26 is expressed, associates with BKalpha
      subunits, and elevates channel voltage- and apparent Ca(2+) sensitivity in
      arterial myocytes to induce vasodilation. This study indicates that arterial
      myocytes express a functional BK channel gamma subunit.

PMID- 24906644
TI  - Characterization of a resident population of adventitial macrophage progenitor
      cells in postnatal vasculature.
AB  - RATIONALE: Macrophages regulate blood vessel structure and function in health and
      disease. The origins of tissue macrophages are diverse, with evidence for local
      production and circulatory renewal. OBJECTIVE: We identified a vascular
      adventitial population containing macrophage progenitor cells and investigated
      their origins and fate. METHODS AND RESULTS: Single-cell disaggregates from adult
      C57BL/6 mice were prepared from different tissues and tested for their capacity
      to form hematopoietic colony-forming units. Aorta showed a unique predilection
      for generating macrophage colony-forming units. Aortic macrophage colony-forming
      unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially
      located, where they were the predominant source of proliferating cells in the
      aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and
      phenotypically distinct from neighboring cells lacking stem cell antigen-1 or
      CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(
      )CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the
      immunophenotypic profile of macrophage progenitors. Adoptive transfer studies
      revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not
      replenished via the circulation from bone marrow or spleen, nor was their
      prevalence diminished by depletion of monocytes or macrophages by liposomal
      clodronate treatment or genetic deficiency of macrophage colony-stimulating
      factor. Rather adventitial macrophage progenitor cells were upregulated in
      hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer
      experiments demonstrating their durable contribution to macrophage progeny
      particularly in the adventitia, and to a lesser extent the atheroma, of
      atherosclerotic carotid arteries. CONCLUSIONS: The discovery and characterization
      of resident vascular adventitial macrophage progenitor cells provides new insight
      into adventitial biology and its participation in atherosclerosis and provokes
      consideration of the broader existence of local macrophage progenitors in other
      tissues.

PMID- 24906645
TI  - Enhancing effects of hydrogen/halogen bonds on sigma-hole interactions involving
      ylide.
AB  - Cooperativity between the H/Cl...C bonds of XH/XCl...CH2PH3 and the P...N
      interaction of CH2PH3...NH3 in XH/XCl...CH2PH3...NH3 (X = F, N3, CN, CCCN, CCF)
      was investigated by performing second-order Moller-Plesset perturbation theory
      (MP2) calculations and quantum theory of atoms in molecules (QTAIM) studies. The
      formation of a hydrogen/halogen bond greatly extends the scope and increases the
      most positive electrostatic potential of the sigma-hole on the outer surface of
      the phosphorus atom. This increases the P...N interaction energy, the electron
      density at the P...N bond critical point, the electrostatic character of the
      P...N interaction, and it decreases the P...N interaction distance. The net
      result is that the formation of a hydrogen/halogen bond enhances the P...N
      interaction, and vice versa. However, the P...N interaction is enhanced by the
      presence of the hydrogen or halogen bond to a much greater degree than the
      hydrogen or halogen bond is enhanced by the P...N interaction. 

PMID- 24906646
TI  - Molecular dynamics simulation of the intercalation behaviors of methane hydrate
      in montmorillonite.
AB  - The formation and mechanism of CH4 hydrate intercalated in montmorillonite are
      investigated by molecular dynamics (MD) simulation. The formation process of CH4
      hydrate in montmorillonite with 1 ~ 8 H2O layers is observed. In the
      montmorillonite, the "surface H2O" constructs the network by hydrogen bonds with
      the surface Si-O ring of clay, forming the surface cage. The "interlayer H2O"
      constructs the network by hydrogen bonds, forming the interlayer cage. CH4
      molecules and their surrounding H2O molecules form clathrate hydrates. The cation
      of montmorillonite has a steric effect on constructing the network and destroying
      the balance of hydrogen bonds between the H2O molecules, distorting the cage of
      hydrate in clay. Therefore, the cages are irregular, which is unlike the ideal
      CH4 clathrate hydrates cage. The pore size of montmorillonite is another impact
      factor to the hydrate formation. It is quite easier to form CH4 hydrate
      nucleation in montmorillonite with large pore size than in montmorillonite with
      small pore. The MD work provides the constructive information to the
      investigation of the reservoir formation for natural gas hydrate (NGH) in
      sediments. 

PMID- 24906647
TI  - Videoconferencing for the pre-operative interaction between patient and surgeon.
AB  - We studied the use of videoconferencing for the pre-operative patient-surgeon
      interaction. Subjects were recruited from otolaryngology patients undergoing
      surgery at a tertiary hospital. They were randomised to a conventional face-to
      face interaction with their surgeon or a videoconference call via tablet
      computer. Afterwards, subjects and surgeons completed questionnaires about the
      experience. Various time points in patient flow were also recorded. Thirty-one
      patients were enrolled and 25 completed the study; five surgeons participated.
      The mean overall patient satisfaction scores were similar in the face-to-face and
      videoconferencing groups (9.88 and 9.89, respectively), as were mean interaction
      times (119 and 82 s, respectively); neither difference was significant. The mean
      waiting times in the pre-operative holding area were not significantly different
      between the groups. Surgeons were satisfied with the videoconferencing and 60%
      indicated they were somewhat likely to incorporate the technology into their
      daily practice. Overall patient satisfaction with a pre-operative patient-surgeon
      interaction via videoconferencing did not differ significantly from that for a
      conventional face-to-face discussion. It is feasible to incorporate
      videoconferencing into a busy surgical practice and there is the potential for
      improved efficiency.

PMID- 24906648
TI  - Screening electroencephalograms are feasible in the emergency department.
AB  - We investigated the feasibility and quality of a wireless, four-channel screening
      electroencephalogram (EEG) device on patients presenting to the emergency
      department (ED) with a possible seizure disorder. A convenience sample was used
      of ED patients presenting with a preliminary diagnosis of syncope, potential
      partial-complex or generalized seizure disorder, head injury with prolonged
      symptoms or acute undiagnosed altered mental status. Study patients had a
      screening EEG in the ED, but the emergency physician and patient were blinded to
      the results of the EEG so that neither patient care nor disposition were affected
      by inclusion in the study. A total of 227 patients were enrolled, with a mean age
      of 56 years. EEG quality was acceptable, i.e. a screening interpretation was able
      to be provided, in 208 of 227 cases (92%). The EEG interpretation was normal in
      65%, identified generalized or focal slowing in 24% and identified sub-clinical
      epileptiform activity in 12% of patients. Screening EEGs performed in the ED are
      feasible, can be acquired with acceptable quality, and may identify sub-clinical
      seizure activity in a significant number of patients.

PMID- 24906649
TI  - Physicians' perceptions of clinical supervision and educational support via
      videoconference: a systematic review.
AB  - We conducted a systematic review of the perceptions of physicians about clinical
      supervision and educational support via videoconferencing. A search of literature
      databases, reference lists and specific journals was performed for relevant
      articles published between 1990 and 2013. A total of 1288 studies were
      identified, of which 13 fulfilled the inclusion criteria for review. Six studies
      concerned education, six concerned clinical practice and one concerned
      supervision. The studies employed a wide variety of methodologies, including
      quantitative and qualitative techniques, so a meta-analysis was not practicable.
      Overall satisfaction and acceptance rates were reported in nine studies, mainly
      using Likert scales. Several positive aspects of videoconferencing were reported,
      including increased education and clinical practice support, and autonomy for
      rural areas. The main negative aspects related to the technology itself, poorer
      interaction and decreased rapport building when using videoconferencing. There is
      a paucity of literature regarding the perceptions of videoconferencing-based
      supervision of junior doctors in rural areas. No studies have considered measures
      of cost effectiveness. More rigorous study design in future research is
      recommended.

PMID- 24906650
TI  - Telemedicine for corneal disease in rural Nepal.
AB  - We evaluated the diagnostic accuracy of slit-lamp photographs interpreted by
      telemedicine compared to a conventional clinical examination. A convenience
      sample of 21 patients with anterior segment disease was enrolled at the Lumbini
      Eye Institute (LEI) in Bhairahawa, Nepal. An ophthalmologist at the LEI examined
      each patient and assigned a diagnosis and follow-up interval; this represented
      the gold standard. An ophthalmic technician also obtained anterior segment
      photographs of each patient. Slit-lamp photographs and clinical histories were
      then uploaded to a server for access by three separate readers. These readers,
      one in Nepal and two in the US, provided a diagnosis and follow-up interval
      independently. The diagnostic agreement between the examiner and all readers was
      good (kappa = 0.75, P < 0.0001). The agreement regarding follow-up interval
      between the examiner and all readers was fair, with a kappa coefficient of 0.32
      (P < 0.0001). However, the agreement was high when comparing the examiner with
      the reviewer in Nepal (kappa = 0.90) and was moderate when comparing the two US
      based readers with each other (kappa = 0.45). In general, the ophthalmologists in
      Nepal recommended more rapid follow-up than their US-based counterparts. Our
      results suggest that the transmission of slit-lamp photographs from satellite
      clinics and eye health screening camps to the LEI and elsewhere for review and
      triage is an effective means of identifying anterior segment pathology.

PMID- 24906652
TI  - Factors influencing stakeholders attitudes toward genetically modified aedes
      mosquito.
AB  - Dengue fever is a debilitating and infectious disease that could be life
      threatening. It is caused by the dengue virus which affects millions of people in
      the tropical area. Currently, there is no cure for the disease as there is no
      vaccine available. Thus, prevention of the vector population using conventional
      methods is by far the main strategy but has been found ineffective. A genetically
      modified (GM) mosquito is among the favoured alternatives to curb dengue fever in
      Malaysia. Past studies have shown that development and diffusion of gene
      technology products depends heavily upon public acceptance. The purpose of this
      study is to identify the relevant factors influencing stakeholders' attitudes
      toward the GM Aedes mosquito and to analyse the relationships between all the
      factors using the structural equation model. A survey was carried out on 509
      respondents from various stakeholder groups in the Klang Valley region of
      Malaysia. Results of the survey have confirmed that public perception towards
      complex issues such as gene technology should be seen as a multi-faceted process.
      The perceived benefit-perceived risk balance is very important in determining the
      most predominant predictor of attitudes toward a GM mosquito. In this study the
      stakeholders perceived the benefit of the GM mosquito as outweighing its risk,
      translating perceived benefit as the most important direct predictor of attitudes
      toward the GM mosquito. Trust in key players has a direct influence on attitudes
      toward the GM mosquito while moral concern exhibited an indirect influence
      through perceived benefits. Other factors such as attitudes toward technology and
      nature were also indirect predictors of attitudes toward the GM mosquito while
      religiosity and engagement did not exhibited any significant roles. The research
      findings serve as a useful database to understand public acceptance and the
      social construct of public attitudes towards the GM mosquito to combat dengue. 

PMID- 24906651
TI  - Evaluation of Simplified Acute Physiology Score 3 performance: a systematic
      review of external validation studies.
AB  - INTRODUCTION: Simplified Acute Physiology Score 3 (SAPS 3) was the first critical
      care prognostic model developed from worldwide data. We aimed to systematically
      review studies that assessed the prognostic performance of SAPS 3 general and
      customized models for predicting hospital mortality in adult patients admitted to
      the ICU. METHODS: Medline, Lilacs, Scielo and Google Scholar were searched to
      identify studies which assessed calibration and discrimination of general and
      customized SAPS 3 equations. Additionally, we decided to evaluate the correlation
      between trial size (number of included patients) and the Hosmer-Lemeshow (H-L)
      statistics value of the SAPS 3 models. RESULTS: A total of 28 studies were
      included. Of these, 11 studies (42.8%) did not find statistically significant mis
      calibration for the SAPS 3 general equation. There was a positive correlation
      between number of included patients and higher H-L statistics, that is, a
      statistically significant mis-calibration of the model (r = 0.747, P <0.001).
      Customized equations for major geographic regions did not have statistically
      significant departures from perfect calibration in 9 of 19 studies. Five studies
      (17.9%) developed a regional customization and in all of them this new model was
      not statistically different from a perfect calibration for their populations.
      Discrimination was at least very good in 24 studies (85.7%). CONCLUSIONS:
      Statistically significant departure from perfect calibration for the SAPS 3
      general equation was common in validation studies and was correlated with larger
      studies, as should be expected, since H-L statistics (both C and H) are strongly
      dependent on sample size This finding was also present when major geographic
      customized equations were evaluated. Local customizations, on the other hand,
      improved SAPS 3 calibration. Discrimination was almost always very good or
      excellent, which gives excellent perspectives for local customization when a
      precise local estimate is needed.

PMID- 24906653
TI  - [Honesty is the best policy].

PMID- 24906654
TI  - Overexpression of Nedd9 is a prognostic marker of human gastric cancer.
AB  - The present study was designed to evaluate the expression and prognostic
      significance of neural precursor cell-expressed, developmentally downregulated 9
      (Nedd9) in patients with gastric cancer. Overexpression of Nedd9 was detected in
      a number of human cancers and was associated with progression and poor prognosis
      of the diseases. The expression of Nedd9 and focal adhesion kinase (FAK) were
      detected using the tissue microarray technique and immunohistochemical method and
      compared with clinicopathological parameters of patients with gastric cancer. The
      expressions of Nedd9 and FAK were upregulated in gastric cancer lesions compared
      with their expression in adjacent non-malignant tissues. High expression of Nedd9
      correlated with age, location of tumor, tumor size, depth of invasion, vessel
      invasion, lymph node metastasis, and distant metastasis, and also with expression
      of FAK. Further, multivariate analysis suggested that expression of Nedd9 and FAK
      were independent prognostic indicators for gastric cancer. Cumulative 5-year
      survival rates of patients with high expression of both Nedd9 and FAK was
      significantly lower than those with low expression of both. Nedd9 was implicated
      in the progression of gastric cancer. Based on the TNM stage, Nedd9 and FAK
      proteins could be useful prognostic marker to predict tumor progression and
      prognosis in gastric cancer. 

PMID- 24906656
TI  - Human genome, environment and medical practice.

PMID- 24906655
TI  - Advances in thymic carcinoma diagnosis and treatment: a review of literature.
AB  - Thymomas account for up to 50 % of anterior mediastinal neoplasms with an
      incidence of 0.13 per 100,000 person-years in the USA. Thymic carcinoma is a rare
      malignancy of the thymus gland distinguished from thymomas as it has a more
      invasive and metastasizing potential conferring poor prognosis. Due to the rarity
      of thymic carcinoma and the great variety of its histological subtypes, there is
      no solid evidence on optimal staging, imaging and treatment guidelines. Herein,
      we systematically review the literature on current clinical practice with regard
      to diagnostic evaluation, histopathological assessment, management and treatment
      of squamous thymic carcinoma.

PMID- 24906657
TI  - Framing comorbidities and co-occurrences in a migraine with aura patient:
      author's reply.

PMID- 24906658
TI  - Splenic hamartomas in two children.
AB  - Hamartomas are extremely rare splenic benign tumours in children. We present two
      cases, both in boys (6 and 8 years old), with left upper quadrant abdominal pain
      that were otherwise asymptomatic. Both patients showed a splenic mass on
      preoperative ultrasonography and magnetic resonance imaging (MRI). One patient
      had a focal splenic mass that was identified preoperatively with contrasted
      computed tomography (CT) scans. Both patients underwent a total splenectomy.
      Although multi-modality imaging findings were described preoperatively, the final
      diagnosis in each case was splenic hamartoma based on histology and
      immunohistochemistry. The postoperative courses were uneventful. 

PMID- 24906659
TI  - Germline mosaicism in X-linked periventricular nodular heterotopia.
AB  - BACKGROUND: X-linked periventricular nodular heterotopia is a disorder of
      neuronal migration resulting from mutations in the filamin A gene. This is an X
      linked dominant condition where most affected patients are female and present
      with seizures. Extra-cerebral features such as cardiac abnormalities and
      thrombocytopenia have also been documented. Loss of function mutations in filamin
      A are predicted to result in prenatal lethality in males. Somatic mosaicism and
      mutations that lead to partial loss of function of the protein are hypothesized
      to explain viability of males reported in the literature. We report the first
      case of germline mosaicism involving a loss of function mutation in filamin A in
      a family where brain MRI, clinical exam, and mutation analysis is normal in both
      biological parents. CASE PRESENTATION: The index patient, a 39 year old female
      with normal development, had her first seizure at 24 years with no evidence of
      any precipitating factors. Brain MRI shows bilateral periventricular nodular
      heterotopia. She has thrombocytopenia and an echocardiogram at age 32 years
      revealed a mildly dilated aortic root and ascending aorta with mild aortic
      regurgitation. The second patient, the 36 year old younger sister of the index
      case, is currently healthy with no evidence of seizures or cardiac abnormalities.
      Her brain MRI is consistent with bilateral periventricular nodular heterotopia.
      The mother is healthy at 57 years of age with a normal brain MRI. The father is
      healthy at 59 years of age with a normal brain MRI. DNA sequencing of lymphocyte
      extracted DNA from the two sisters shows a c.2002C > T transition in exon 13 of
      filamin A resulting in a p.Gln668Ter mutation. This nonsense mutation was not
      detected in peripheral blood lymphocytes from the unaffected parents. CONCLUSION:
      This report provides evidence for germline mosaicism in filamin A-associated
      periventricular nodular heterotopia. This case must now be considered when
      providing genetic counseling to families where a proband presents as an isolated
      case and parental investigations are unremarkable.

PMID- 24906661
TI  - Celebrating the 80th anniversary of Antonie van Leeuwenhoek: a special issue.

PMID- 24906660
TI  - Aquimarina atlantica sp. nov., isolated from surface seawater of the Atlantic
      Ocean.
AB  - A taxonomic study was carried out on strain 22II-S11-z7(T), which was isolated
      from the surface seawater of the Atlantic Ocean. The bacterium was found to be
      Gram-negative, oxidase negative and catalase positive, long-rod shaped, and
      gliding. Growth was observed at salinities of 1-5 % and at temperatures of 10-41 
      degrees C. The isolate was capable of hydrolysing gelatin and Tween 80 and able
      to reduce nitrate to nitrite, but unable to degrade aesculin. Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that strain 22II-S11-z7(T)
      belongs to the genus Aquimarina, with highest sequence similarity to Aquimarina
      megaterium XH134(T) (98.31 %), followed by Aquimarina macrocephali JAMB N27(T)
      (96.59 %); other species of the genus Aquimarina shared 93.63-96.08 % sequence
      similarity. The ANI value between strain 22II-S11-z7(T) and A. megaterium
      XH134(T) was found to be 91.86-91.81 %. The DNA-DNA hybridization estimated value
      between strain 22II-S11-z7(T) and A. megaterium XH134(T) was 47.7 +/- 2.6 %. The
      principal fatty acids were identified as Summed Feature 3 (C16:1 omega7c/omega6c,
      as defined by the MIDI system; 8.1 %), SummedFeature 9 (iso-C17:1 omega7c/C16:110
      methyl; 6.8 %), iso-C15:0 G (11.3 %), iso-C15:0 (24.9 %), iso-C16:0 (5.7 %),
      C16:0 (5.2 %), iso-C15:0 3OH (6.4 %) and iso-C17:0 3OH (21.5 %). The G+C content
      of the chromosomal DNA was determined to be 32.99 mol %. The respiratory quinone
      was determined to be MK-6 (100 %). Phosphatidylethanolamine, two unidentified
      aminolipids, five unidentified phospholipids and two unidentified lipids were
      found to be present. The combined genotypic and phenotypic data show that strain
      22II-S11-z7(T) represents a novel species within the genus Aquimarina, for which
      the name Aquimarina atlantica sp. nov. is proposed, with the type strain 22II-S11
      z7(T) (=MCCC 1A09239(T) = KCTC 42003(T)). 

PMID- 24906662
TI  - Clinical significance of circulating tumor cells (CTCs) with respect to optimal
      cut-off value and tumor markers in advanced/metastatic breast cancer.
AB  - BACKGROUND: Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15
      3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating
      tumor cells (CTCs) are also detected in patients with advanced or metastatic
      breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal
      cut-off value, to evaluate the prognostic utility of CTC count, and to clarify
      whether CTC count could provide information in addition to CEA and CA15-3.
      METHODS: We studied 98 MBC patients enrolled between June 2007 and March 2013. To
      quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured
      simultaneously. CTCs were counted using the CellSearchTM System. The CTC count
      was dichotomized as 0 (CTC-negative) or >=1 (CTC-positive). The clinical
      significance of CTCs was evaluated in terms of its relationship with levels of
      CEA and CA15-3. Associations between qualitative variables were evaluated using
      the chi-square test. In order to evaluate the predictive value of CTCs for
      advanced or metastatic breast cancer, multivariate Cox proportional hazards
      modeling was used to calculate hazard ratios. RESULTS: With a CTC cut-off value
      of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive
      patients. Patients in the CTC-positive group had worse survival than those in the
      CTC-negative group (p < 0.0001). Seventy-one patients (72.4 %) had TM data at the
      time of CTC testing. To study the relationship between CTCs and TMs, we divided
      patients into normal TM and high TM groups. In the normal TM group, the CTC
      negative patients had statistically significant survival than the CTC-positive
      patients (p = 0.005). The data suggested that CTC count could provide additional
      prognostic information beyond TMs for advanced/metastatic breast cancer. In
      multivariate analysis, the only significant predictor of overall survival was CTC
      >= 1 (hazard ratio, 3.026; 95 % confidence interval 1.350-6.784). CONCLUSION: We
      found that a CTC cut-off value of 1 is appropriate in patients with
      advanced/metastatic breast cancer. CTCs could yield additional information beyond
      CEA and CA15-3.

PMID- 24906663
TI  - Subcutaneous omacetaxine mepesuccinate in patients with chronic myeloid leukemia
      in tyrosine kinase inhibitor-resistant patients: review and perspectives.
AB  - The treatment of chronic myelogenous leukemia (CML) has been revolutionized by
      the introduction of tyrosine kinase inhibitors (TKI), however, with the exception
      of ponatinib, none of the existing licensed agents seem to eradicate the
      reservoir of Philadelphia positive stem cells, thus sustaining the disease over
      time, and retaining activity in cells and patients harboring an ABL T315I
      mutation. Omacetaxine mepesuccinate (OMA), formerly known as homoharringtonine,
      is a cephalotaxus alkaloid derivative and an inhibitor of protein synthesis
      without tyrosine kinase activity developed 35 years ago by Chinese investigators
      in the treatment of leukemia. This compound demonstrates specific activity in CML
      and has been recently commercialized in the U.S. for the treatment of patients in
      chronic or accelerated phase CML with resistance and/or intolerance to two or
      more tyrosine kinase inhibitors or harboring a T315I ABL mutation. CML patients
      with a T315I mutation experienced poor overall survival rates in the pre
      ponatinib era (median for CP CML 24 months). Recent studies demonstrate the
      activity of OMA even in such a poor prognosis population. We hereby detail the
      development of OMA as an effective agent in CML in these patients.

PMID- 24906664
TI  - Subclinical atherosclerosis and ambulatory blood pressure in children with
      metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome (MS) has reached epidemic proportions
      worldwide. This syndrome is associated with cardiovascular risk factors,
      including functional and structural cardiac and vascular changes. The aim of our
      study was to evaluate subclinical atherosclerosis and its associated risk factors
      in children with MS. METHODS: The study cohort comprised 52 children with MS and
      38 age- and sex-matched healthy children. The diagnosis of MS was made according
      to criteria adopted by the World Health Organization. Blood pressure based on 24
      h ambulatory blood pressure monitoring (ABPM), carotid intima-media thickness
      (cIMT), carotid distensibility coefficient (DC) and flow-mediated endothelium
      dependent dilation (EDD) were assessed in all children. RESULTS: We found a
      significantly higher cIMT in children with MS than in healthy children, but
      carotid DC and flow-mediated EDD were lower in the former. Multivariate analysis
      revealed that a higher cIMT was independently associated with a higher nighttime
      systolic blood pressure (SBP) and lower high-density lipoprotein-cholesterol
      (beta = 0.386, p = 0.011 and beta = 0.248, p = 0.042, respectively). Also, higher
      nighttime SBP remained an independent predictor of lower DC (beta = 0.495, p =
      0.009), and higher 24-h SBP was the only independent predictor for a lower EDD
      (beta = 0.532, p = 0.004). CONCLUSIONS: Atherosclerotic vascular changes were
      common among our pediatric patients with MS and easily determined by high
      resolution ultrasound imaging. In particular, subclinical atherosclerosis was
      clearly associated with nocturnal or 24-h systolic hypertension as measured by
      ABPM. We therefore recommend that subclinical vascular changes and AMBP
      measurements should be used as diagnostic markers to predict atherosclerotic
      risks in this pediatric patient group.

PMID- 24906667
TI  - Pediatric conjunctivitis.

PMID- 24906665
TI  - Long-term, low-dose prophylaxis against urinary tract infections in young
      children.
AB  - Urinary tract infection (UTI) affects about 2 % of boys and 8 % of girls during
      the first 6 years of life with Escherichia coli as the predominant pathogen.
      Symptomatic UTI causes discomfort and distress, and carries a risk of inducing
      renal damage. The strong correlation between febrile UTI, dilating vesicoureteral
      reflux (VUR), and renal scarring led to the introduction of antibiotic
      prophylaxis for children with VUR to reduce the rate of UTI recurrence. It became
      common practice to use prophylaxis for children with VUR and other urinary tract
      abnormalities. This policy has been challenged because of a lack of scientific
      support. Now, randomized controlled studies are available that compare
      prophylaxis to no treatment or placebo. They show that children with normal
      urinary tracts or non-dilating VUR do not benefit from prophylaxis. Dilating VUR
      may still be an indication for prophylaxis in young children. After the first
      year of life, boys have very few recurrences and do not benefit from prophylaxis.
      Girls with dilating VUR, on the other hand, are more prone to recurrences and
      benefit from prophylaxis. There has been a decline in the use of prophylaxis due
      to questioning of its efficacy, increasing bacterial resistance, and a propensity
      to low adherence to medication. Alternative measures to reduce UTI recurrences
      should be emphasized. However, in selected patients carefully followed,
      prophylaxis can protect from recurrent UTI and long-term sequelae. 1. There is a
      strong correlation between UTI, VUR, and renal scarring. 2. Children with normal
      urinary tracts or non-dilating VUR do not benefit from prophylaxis. 3. Young
      children, mainly girls, with dilating VUR are at risk of recurrent UTI and
      acquired renal scarring and seem to gain from antibiotic prophylaxis. 4.
      Increasing bacterial resistance and low adherence with prescribed medication is a
      major obstacle to successful antibiotic prophylaxis. 

PMID- 24906668
TI  - Herpes simplex keratitis.

PMID- 24906669
TI  - Management of anterior segment trauma.

PMID- 24906670
TI  - Angle-closure glaucoma.

PMID- 24906671
TI  - Medication induced retinal side effects.

PMID- 24906672
TI  - Ocular manifestations seen in HIV.

PMID- 24906673
TI  - A review of optic neuropathies.

PMID- 24906674
TI  - Retinopathy of prematurity.

PMID- 24906675
TI  - Thyroid eye disease for the primary care physician.

PMID- 24906676
TI  - Age-related NADH oxidase (arNOX)-catalyzed oxidative damage to skin proteins.
AB  - Age-related NADH oxidase (arNOX), a cell surface-located hydroquinone oxidase
      capable of superoxide generation, appears at age 30 and increases with age
      thereafter. The ectodomain of arNOX is shed from the cell surface into body
      fluids including sera and saliva where its activity was measured
      spectrophotometrically using a reduction of ferricytochrome c as a measure of
      superoxide generation. The autofluorescence of advanced glycation end products
      correlates with epidermal arNOX activity as well. To demonstrate protein cross
      linking, a fluorescence-labeled analog of tyrosine, tyramine, that would react
      with proteins carrying arNOX-generated tyrosyl radicals was used. The assay
      demonstrated the potential for arNOX-induced oxidative damage (dityrosine
      formation) to human collagen and elastin and to other surface proteins of intact
      human embryo fibroblasts and frozen sections from epidermal punch biopsies. The
      findings support a role for arNOX as a major source of oxidative damage leading
      to cross-linking of skin proteins. 

PMID- 24906677
TI  - The effects of aging on the brain activation pattern during a speech perception
      task: an fMRI study.
AB  - In the present study, brain activation associated with speech perception
      processing was examined across four groups of adult participants with age ranges
      between 20 and 65 years, using functional MRI (fMRI). Cognitive performance
      demonstrates that performance accuracy declines with age. fMRI results reveal
      that all four groups of participants activated the same brain areas. The same
      brain activation pattern was found in all activated areas (except for the right
      superior temporal gyrus and right middle temporal gyrus); brain activity was
      increased from group 1 (20-29 years) to group 2 (30-39 years). However, it
      decreased in group 3 (40-49 years) with further decreases in group 4 participants
      (50-65 years). Result also reveals that three brain areas (superior temporal
      gyrus, Heschl's gyrus and cerebellum) showed changes in brain laterality in the
      older participants, akin to a shift from left-lateralized to right-lateralized
      activity. The onset of this change was different across brain areas. Based on
      these findings we suggest that, whereas all four groups of participants used the
      same areas in processing, the engagement and recruitment of those areas differ
      with age as the brain grows older. Findings are discussed in the context of
      corroborating evidence of neural changes with age. 

PMID- 24906678
TI  - Low HDL cholesterol but not high LDL cholesterol is independently associated with
      subclinical coronary atherosclerosis in healthy octogenarians.
AB  - AIM OF THE STUDY: Although low-density lipoprotein cholesterol (LDL-C) has been
      consistently demonstrated a predictor of atherosclerotic disease in a large
      spectrum of clinical settings, among individuals aged of 80 years or older this
      concept is uncertain. This study was evaluated in a carefully selected population
      if the association between LDL-C and coronary atherosclerotic burden remains
      significant in the very elderly. METHODS: Individuals aged of 80 years or older
      (n = 208) who spontaneously sought primary prevention care and have never
      manifested cardiovascular disease, malnutrition, neoplastic or consumptive
      disease were enrolled for a cross-sectional analysis. Medical evaluation,
      anthropometric measurements, blood tests and cardiac computed tomography were
      obtained. RESULTS: In analyses adjusted for age, gender, diabetes, systolic and
      diastolic blood pressure, smoking and statin therapy, no association was found
      between coronary calcium score (CCS) and LDL-C [1.79 (0.75-4.29)]. There was no
      association between triglycerides and CCS. The association between high-density
      lipoprotein cholesterol (HDL-C) and CCS was significant and robust in unadjusted
      [0.32 (0.15-0.67)] as well as in the fully adjusted analysis [0.34 (0.15-0.75)].
      CONCLUSION: The present study confirms in a healthy cohort of individuals aged of
      80 years or more that while the association between LDL-C and coronary
      atherosclerosis weakens with aging, the opposite occurs with the levels of HDL-C.

PMID- 24906679
TI  - Feasibility of sensory tongue stimulation combined with task-specific therapy in
      people with spinal cord injury: a case study.
AB  - BACKGROUND: Previous evidence suggests the effects of task-specific therapy can
      be further enhanced when sensory stimulation is combined with motor practice.
      Sensory tongue stimulation is thought to facilitate activation of regions in the
      brain that are important for balance and gait. Improvements in balance and gait
      have significant implications for functional mobility for people with incomplete
      spinal cord injury (iSCI). The aim of this case study was to evaluate the
      feasibility of a lab- and home-based program combining sensory tongue stimulation
      with balance and gait training on functional outcomes in people with iSCI.
      METHODS: Two male participants (S1 and S2) with chronic motor iSCI completed 12
      weeks of balance and gait training (3 lab and 2 home based sessions per week)
      combined with sensory tongue stimulation using the Portable Neuromodulation
      Stimulator (PoNS). Laboratory based training involved 20 minutes of standing
      balance with eyes closed and 30 minutes of body-weight support treadmill walking.
      Home based sessions consisted of balancing with eyes open and walking with
      parallel bars or a walker for up to 20 minutes each. Subjects continued daily at
      home training for an additional 12 weeks as follow-up. RESULTS: Both subjects
      were able to complete a minimum of 83% of the training sessions. Standing balance
      with eyes closed increased from 0.2 to 4.0 minutes and 0.0 to 0.2 minutes for S1
      and S2, respectively. Balance confidence also improved at follow-up after the
      home-based program. Over ground walking speed improved by 0.14 m/s for S1 and
      0.07 m/s for S2, and skilled walking function improved by 60% and 21% for S1 and
      S2, respectively. CONCLUSIONS: Sensory tongue stimulation combined with task
      specific training may be a feasible method for improving balance and gait in
      people with iSCI. Our findings warrant further controlled studies to determine
      the added benefits of sensory tongue stimulation to rehabilitation training.

PMID- 24906680
TI  - Iterative reconstruction improves image quality and preserves diagnostic accuracy
      in the setting of blunt solid organ injuries.
AB  - This study aims to investigate the effect of iterative reconstruction (IR) on
      MDCT image quality and radiologists' ability to diagnose and grade blunt solid
      organ injuries. One hundred (100) patients without and 52 patients with solid
      organ injuries were scanned on a 64-slice MDCT scanner using reference 300 mAs,
      120 kVp, and fixed 75 s delay. Raw data was reconstructed using filtered back
      projection (FBP) and three levels of iterative reconstruction (Philips iDose
      levels 2, 4, and 6). Four emergency radiologists, blinded to the reconstruction
      parameters and original interpretation, independently reviewed each case,
      assessed image quality, and assigned injury grades. Each reader was then asked to
      determine if they thought that IR was used and, if so, what level. There was no
      significant difference in diagnostic accuracy between FBP and the various IR
      levels or effect on the detection and grading of solid organ injuries (p > 0.8).
      Images reconstructed using iDose level 2 were judged to have the best overall
      image quality (p < 0.01). The radiologists had high sensitivity in detecting if
      IR was used (80 %, 95 % CI 76-84 %). IR performed comparably to FBP with no
      effect on radiologist ability to accurately detect and grade blunt solid organ
      injuries.

PMID- 24906681
TI  - The implementation of Mask-Ed: reflections of academic participants.
AB  - This paper profiles the findings from a study that explored the perspectives and
      experiences of nurse educators who implemented a novel simulation approach termed
      Mask-Ed. The technique involves the educator wearing a silicone mask and or body
      parts and transforming into a character. The premise of this approach is that the
      masked educator has domain specific knowledge related to the simulation scenario
      and can transmit this to learners in a way that is engaging, realistic,
      spontaneous and humanistic. Nurse educators charged with the responsibility of
      implementing Mask-Ed in three universities were invited to participate in the
      study by attending an introductory workshop, implementing the technique and then
      journaling their experiences, insights and perspectives over a 12 month period.
      The journal entries were then thematically analysed. Key themes were categorised
      under the headings of Preparation, Implementation and Impact; Reflexivity and
      Responsiveness; Student Engagement and Ownership; and Teaching and Learning. Mask
      Ed is a simulation approach which allows students to interact with the
      'characters' in humanistic ways that promote person-centred care and therapeutic
      communication. This simulation approach holds previously untapped potential for a
      range of learning experiences, however, to be effective, adequate resourcing,
      training, preparation and practice is required. 

PMID- 24906682
TI  - Reply from authors re: Homayoun Zargar, Riccardo Autorino, Oktay Akca, Jihad H.
      Kaouk. Anatomic complexity of renal masses and outcomes of minimally invasive
      partial nephrectomy: do we have an answer? Eur Urol 2014;66:894-6: contact
      surface area, a novel parameter, may outperform nephrometry systems in predicting
      complexity of partial nephrectomy surgery.

PMID- 24906683
TI  - Evaluation of high-risk clinicopathological indicators in gastrointestinal
      stromal tumors for prognosis and imatinib treatment outcome.
AB  - BACKGROUND: Although the clinical benefit of imatinib adjuvant therapy for high
      risk patients with gastrointestinal stromal tumor (GIST) has been proven, the
      recurrence rate still remains high. This study aimed to sub-divide high-risk GIST
      patients with some "very high-risk" factors for more precise prognostic
      indicator, and possible association with efficiency of imatinib adjuvant therapy.
      METHODS: Clinicopathological data were confirmed by pathological diagnosis and
      clinical records. Recurrence-free survivals (RFS) were evaluated in 370 GIST
      patients (212 cases as test cohort and 158 cases as validation cohort) and 48
      high-risk GISTs with imatinib adjuvant therapy after R0 resection. RESULTS:
      Mitosis count > 10/50 high-power fields (HPF) and serosal invasion are
      independent prognostic factors for RFS of GIST patients. Mitosis count > 10/50HPF
      and serosal invasion can sub-divide high-risk GIST patients effectively and
      significantly improve the area under the curve (AUC) of receiver operating
      characteristics (ROC) curve for prognostic indicator both in test and validation
      cohort. Patients with serosal invasion after R0 resection showed a poorer
      prognosis with imatinib adjuvant therapy. CONCLUSIONS: Sub-division of high-risk
      GIST patients helps to more precisely predicting the prognosis. Serosal invasion
      may be an adverse predictive factor in high-risk patients and imatinib treatment
      outcome.

PMID- 24906684
TI  - A cross sectional observational study to estimate herd level risk factors for
      Leptospira spp. serovars in small holder dairy cattle farms in southern Chile.
AB  - BACKGROUND: The south of Chile constitutes the main cattle milk producing area of
      the country. Regarding leptospirosis control in Chile, there is neither an
      official program nor an epidemiological characterization of smallholder dairy
      farms. This study was carried out to determine Leptospira seroprevalence and to
      evaluate risk factors associated with seropositivity at herd level in smallholder
      bovine dairy herds in southern Chile.A cross-sectional study was conducted, and a
      convenient sample of 1,537 apparently healthy dairy cows was included in the
      study. Individual blood samples were taken and examined for six selected
      reference Leptospira serovars by the Microscopic Agglutination Test (MAT).
      RESULTS: Of the included herds 75% (52/69) showed serological titers against one
      or more Leptospira serovar. Leptospira borgpetersenii serovar Hardjo was the
      serovar most frequently (81%) reported from animals with positive results. The
      variables considered risk factors for Leptospira seropositivity were calve
      natural breeding system, using a specific calving area and vaccination against
      Leptospira. Adult cows in contact with calves weaned, proved to be a protective
      factor against infection. CONCLUSIONS: Herds neglecting the management practices
      mentioned in this study could represent an important source of Leptospira
      infection for other herds in the same geographic area, as well as for other
      animal species.

PMID- 24906687
TI  - Biomechanical analysis of iliac screw fixation in spinal deformity
      instrumentation.
AB  - BACKGROUND: High rates of iliac screw fixation failures have been reported in
      spinopelvic instrumentations. The objective was to assess the iliac screw loads
      as functions of instrumentation variables. METHODS: Spinopelvic instrumentations
      of six neuromuscular scoliosis were simulated using patient-specific modeling
      techniques to evaluate the intra- and postoperative iliac screw loads as
      functions of instrumentation variables: the combined use of sacral screws, the
      uses of lateral offset connectors and cross-rod connectors, and the iliac screw
      insertion point and trajectory. FINDINGS: Sacral screws, lateral connectors and
      the iliac screw insertion point had significant effects on iliac screw axial
      forces (69-297N) and toggle moments (0.8-2.9Nm) (p<0.05). The addition of sacral
      screws made the iliac screw forces lower for some functional loads but higher for
      other functional loads, and resulted in an increase of intraoperative screw
      forces when attaching the rods onto these additional screws. When lateral offset
      connectors were used, the toggle moments were 16% and 25% higher, respectively
      for the left and right sides. Inserting iliac through the sacrum resulted in 17%
      lower toggle moment compared to insertion through the iliac crest. Cross-rod
      connectors had no significant effect on the intraoperative iliac screw forces.
      Postoperative functional loading had an important effect (additional 34% screw
      axial force and 18% toggle moment). INTERPRETATION: It is possible to reduce the
      iliac screw loads by adapting instrumentation variables and strategies. Reducing
      the loads could decrease the risk of failure associated with iliac screw
      fixations.

PMID- 24906686
TI  - Enhanced Glutamine Availability Exerts Different Effects on Protein and Amino
      Acid Metabolism in Skeletal Muscle From Healthy and Septic Rats.
AB  - BACKGROUND: Enhanced glutamine (GLN) intake may affect the catabolism of branched
      chain amino acids (BCAAs; valine, leucine, and isoleucine), which play a
      regulatory role in protein turnover. We examined the effects of enhanced GLN
      availability on leucine oxidation, amino acid concentrations, and protein
      metabolism in muscles from healthy and septic rats. METHODS: Cecal ligation and
      puncture were used as a model of sepsis. Twenty-four hours after surgery, the
      soleus (SOL, red muscle) and the extensor digitorum longus (EDL, white muscle)
      were incubated in medium containing 0.5 or 2.0 mM GLN. Protein breakdown, protein
      synthesis, and leucine oxidation were determined via 3-methylhistidine release,
      muscle L-[1-(14)C]leucine radioactivity, and the radioactivity of released
      (14)CO2, respectively. RESULTS: In muscles from septic animals, increased
      proteolysis and leucine oxidation and decreased protein synthesis were detected.
      These effects were more pronounced in the EDL. In septic muscles, the addition of
      GLN decreased leucine oxidation in both muscles and increased protein synthesis
      in the EDL. In muscles from untreated animals, decreased leucine oxidation after
      the addition of GLN to the medium was associated with decreased protein synthesis
      in the SOL and decreased concentrations of serine, glycine, histidine, alanine,
      arginine, proline, and lysine in both muscles. CONCLUSIONS: White muscle fibers
      are more sensitive to septic stimuli than red fibers are. In sepsis, enhanced GLN
      intake may ameliorate GLN deficiency, inhibit BCAA catabolism, and stimulate
      protein synthesis. In the healthy state, surplus of GLN may lead to severe
      alterations in the intramuscular concentration of several amino acids and impair
      protein synthesis.

PMID- 24906685
TI  - The strength of the antibody response to the nematode Ascaris lumbricoides
      inversely correlates with levels of B-Cell Activating Factor (BAFF).
AB  - BACKGROUND: B-Cell Activating Factor (BAFF) is a cytokine regulating antibody
      production. Polymorphisms in the gene encoding BAFF were associated with the
      antibody response to Ascaris but not to mite allergens. In the present study we
      evaluated the relationship between BAFF and specific antibodies against Ascaris
      and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA
      and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was
      analyzed by flow cytometry. RESULTS: Individuals with specific IgE levels to
      Ascaris >75th percentile had lower levels of soluble BAFF; those with specific
      IgG levels to Ascaris >75th percentile had reduced BAFF mRNA. Total IgE and
      specific IgE to mites were not related to BAFF levels. There were no differences
      in soluble BAFF or mRNA levels between asthmatics and controls. There was an
      inverse relationship between the cell-surface expression of BAFF-R on CD19+ B
      cells and BAFF levels at the transcriptional and protein level. CONCLUSIONS:
      These findings suggest that differences in BAFF levels are related to the
      strength of the antibody response to Ascaris.

PMID- 24906688
TI  - Reliability and validity of Leicester Cough Questionnaire Korean version.
AB  - The Leicester Cough Questionnaire (LCQ) is a self-administered questionnaire
      developed in England and validated for reliability. We developed a Korean
      translation of this questionnaire by applying a sequential forward and backward
      translation approach. The purpose of this study is to validate the Korean version
      of the LCQ (LCQ-K) in Korean patients with chronic cough. A multicenter
      prospective study was undertaken with 100 chronic cough patients who consented to
      participate in the study. The LCQ-K includes eight physical items, seven
      psychological items, and four social items. Visual analog scale (VAS) of cough,
      Borg Cough Scale (BCS), and Short Form-36 (SF-36) were used as external
      comparators. Participants included 52 women and 48 men with ages ranging from 18
      years to 69 years. The concurrent validity comparing LCQ-K to VAS, BCS, and SF-36
      yielded statistically significant Pearson correlation coefficients. The LCQ-K
      showed good reliability in three domains, with Cronbach's alpha coefficients
      ranging from 0.84 to 0.87 (total: 0.91). Test-retest reliability was investigated
      with single measure intraclass correlation coefficients, which were found to be
      practically and statistically significant (p = 0.005). Responsiveness was
      validated by effective size ranging from 1.16 to 1.40 in each domain. LCQ-K is a
      reliable, valid, and responsive disease-specific questionnaire for assessing
      symptoms and quality of life of Korean patients with chronic cough.

PMID- 24906691
TI  - MRI features of solid pseudopapillary neoplasm of the pancreas.
AB  - PURPOSE: To evaluate the magnetic resonance imaging (MRI) findings of solid
      pseudopapillary neoplasm (SPN) of the pancreas. METHODS AND MATERIALS: From
      January 2006 to December 2013, 41 patients with SPN of the pancreas were
      retrospectively evaluated. Inclusion criteria were the execution of an MR
      examination and tumor resection with an histopathological evaluation at our
      Institute. Exclusion criteria were the execution of an MR examination at other
      centers (14/41) and the execution of CT or ultrasonography (10/41) at our
      Institute. The qualitative analysis evaluated: location (head/body-tail), shape
      (round/oval/lobulated), margins (regular/irregular), and signal intensity on T1-
      and T2-weighted images compared to the surrounding pancreas (hypo-, iso-, or
      hyperintense and homogeneous or heterogeneous), appearance of MPD and the
      secondary ducts, and the presence of metastases and/or vascular involvement. The
      quantitative analysis included: maximum size of the lesion, wall thickness, and
      maximum diameter of the main pancreatic duct (MPD). RESULTS: The population
      comprised 17 women (median age: 31 year) with a median tumor size of 50.6 mm, a
      median wall thickness of 2 mm and median diameter of the MPD of 1.8 mm. 9/17 were
      at the head; 8/17 on the body/tail: respectively, 8/17 round, 6/17 oval, and 3/17
      lobulated. All showed regular margins. On T1-weighted images 8/17 appeared
      homogeneously hypointense, 7/17 heterogeneously hypointense, and 2/17
      heterogeneously hyperintense. On T2-weighted images 1/17 appeared homogeneously
      hyperintense and 16/17 heterogeneously hyperintense. No secondary ducts
      dilatations were detected. During the follow-up, one patient presented disease
      recurrence 48 months after surgery. CONCLUSIONS: MR imaging features can be
      highly suggestive for the diagnosis of SPN.

PMID- 24906690
TI  - Relationships between KRAS mutation status and baseline radiographic distribution
      of disease in patients with stage IV colorectal cancer.
AB  - PURPOSE: KRAS oncogene testing is recommended in all patients with metastatic
      colorectal cancer due to its impact on treatment selection, but we do not know if
      KRAS genotype affects extent or pattern of metastases. We investigated whether
      the initial radiographic distribution of disease varies by KRAS genotype in stage
      IV colorectal cancer. MATERIALS AND METHODS: This retrospective study of 65
      patients with stage IV colorectal cancer was derived from an institutional
      clinical trials database. Inclusion criteria required KRAS testing and
      pretreatment CT studies to be available. Disease burden was characterized by two
      radiologists. RESULTS: Univariate analysis showed that there was no significant
      difference in the initial distribution of disease between KRAS mutant and wild
      type tumors (P > 0.05). Exploratory analyses showed that patients with poorly
      differentiated histology had a statistically significant increase in hepatic
      metastases in the presence of KRAS mutations vs. KRAS wild type genotype (median
      5.0 vs. 0.5, P = 0.02). CONCLUSIONS: No overall difference was found in the
      initial radiographic distribution of disease between KRAS mutant and wild type
      colorectal cancers. Patients with both poorly differentiated histology and KRAS
      mutations had more liver metastases in subgroup analyses.

PMID- 24906692
TI  - Prognosis of patients with alpha1-antitrypsine deficiency on long-term oxygen
      therapy.
AB  - INTRODUCTION: Data on patients with alpha1-antitrypsine deficiency (AATD) on long
      term oxygen therapy (LTOT) is sparse. The aim of this study was to present the
      incidence of patients with AATD on LTOT, and compare their characteristics,
      comorbidities and prognosis (lung transplantation, termination of LTOT, and
      survival) with COPD patients without AATD. METHODS: A National prospective study
      of all COPD patients who started LTOT for the first time in the period 01.11.1994
      to 31.12.2010. RESULTS: Among the 21,964 patients on LTOT, 234 patients had AATD.
      AATD patients were more often males and were on average about 17 years younger
      than patients without AATD. Cardio-vascular diseases and diabetes mellitus were
      significantly less prevalent among patients with AATD (60.4% versus 70.3% (P <
      0.001) and 4.7% versus 12.2% (P < 0.001)), whereas osteoporosis was more frequent
      (28.5% versus 20.4%, p = 0.002. Eighty-nine (38.0%) AATD patients and 173 (0.8%)
      non-AATD patients were lung transplanted in the study period. Median survival was
      8.7 years in AATD patients with lung transplantation, 3.3 years in AATD patients
      without lung transplantation, 6.3 years in non-AATD patients with lung
      transplantation, and 1.6 years in non-AATD without lung transplantation. Even
      after adjustment for gender, age, comorbidities, and the time between start of
      LTOT and lung transplantation, patients with AATD had a lower risk of death
      compared to non-AATD patients (Hazard ratio 0.73 (95% CI: 0.62-0.86; P < 0.001).
      CONCLUSIONS: Compared with COPD without AATD, AATD patients are younger, more
      often males, have a lower prevalence of cardio-vascular diseases and diabetes
      mellitus, and higher prevalence of osteoporosis. Moreover, they have better
      prognosis, partly due to greater chance of receiving a lung transplantation.

PMID- 24906689
TI  - Animal models of inflammatory bowel disease: a review.
AB  - Inflammatory bowel disease (IBD) represents a group of idiopathic chronic
      inflammatory intestinal conditions associated with various areas of the GI tract,
      including two types of inflammatory conditions, i.e., ulcerative colitis (UC) and
      Crohn's disease (CD). Both UC and CD are chronic inflammatory disorders of the
      intestine; in UC, inflammation starts in the rectum and generally extends
      proximally in a continuous manner through the entire colon. Bloody diarrhea,
      presence of blood and mucus mixed with stool, accompanied by lower abdominal
      cramping, are the characteristic symptoms of the disease. While in CD,
      inflammatory condition may affect any part of the GI tract from mouth to anus. It
      mainly causes abdominal pain, diarrhea, vomiting and weight loss. Although the
      basic etiology of IBD is unknown, there are several factors that may contribute
      to the pathogenesis of this disease, such as dysregulation of immune system or
      commensal bacteria, oxidative stress and inflammatory mediators. In order to
      understand these different etiological factors, a number of experimental models
      are available in the scientific research, including chemical-induced,
      spontaneous, genetically engineered and transgenic models. These models represent
      a major source of information about biological systems and are clinically
      relevant to the human IBD. Since there is less collective data available in one
      single article discussing about all these models, in this review an effort is
      made to study the outline of pathophysiology and various types of animal models
      used in the research study of IBD and other disease-related complications. 

PMID- 24906693
TI  - Mass imaging of ketamine in a single scalp hair by MALDI-FTMS.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) coupled
      with mass spectrometry imaging (MSI) is a rapidly emerging technology that
      produces distribution maps of small pharmaceutical molecules in situ in tissue
      sections. Segmental hair analysis provides useful information regarding the state
      and history of drug use. A preliminary MALDI-Fourier transform ion cyclotron
      resonance (FTICR)-MSI method was developed for direct identification and imaging
      of ketamine in hair samples. After decontamination, the scalp hair samples from
      ketamine users were scraped gently and were fixed onto a stainless steel MALDI
      plate using double-sided adhesive tape. A Bruker 9.4 T solariX FTICR mass
      spectrometer with continuous accumulation of selected ions function was used in
      the positive ion mode. Four single hairs from the same drug abuser were analyzed.
      Three of four single hairs demonstrated ketamine spatial distribution, while only
      traces of ketamine were identified in the other one. The platform could provide
      detection power of ketamine down to the 7.7 ng/mg level in hair. MALDI-FTICR-MSI
      demonstrated the drug distribution over the whole hair length with higher spatial
      resolution compared with the traditional LC-MS/MS method after scissor cutting.
      Greater caution is needed in the interpretation of a single hair result because
      of the considerable variations in the growth rate and sample collection.

PMID- 24906694
TI  - A 41-gene signature derived from breast cancer stem cells as a predictor of
      survival.
AB  - PURPOSE: The aim of this study was to evaluate the ability of a 41-gene signature
      derived from breast cancer stem cells (BCSCs) to estimate the risk of metastasis
      and survival in breast cancer patients. METHODS: The centroid expression of the
      41-gene signature derived from BCSCs was applied as the threshold to classify
      patients into two separate groups--patients with high expression (high-EL) of the
      prognostic signature and patients with low expression (low-EL). The predictive
      ability of the 41-gene signature was evaluated by Cox regression model and was
      compared against other popular tests, such as Oncotype and MammaPrint. RESULTS:
      Our results showed that the 41-gene prognostic signature was significantly
      associated with age (P = .0351) and ER status (P = .0095). The analysis indicated
      that patients in the high-EL group had a worse prognosis than those in the low-EL
      group in terms of both overall survival (OS: HR, 2.05, P = .009) and distant
      metastasis-free survival (DMFS: HR, 2.24, P = .002). Additionally, the 41-gene
      signature was an independent risk factor and separates patients based on estrogen
      receptor status. While comparable to Oncotype, the analysis demonstrated that the
      41-gene signature had a better prognostic value in predicting DMFS and OS than
      AOL, NPI, St. Gallen, Veridex, and MammaPrint. CONCLUSIONS: This study confirms
      the utility of the 41-gene signature and adds to the growing evidence that gene
      expression signatures of BCSCs have clinical potential to predict patient outcome
      and aid in treatment choice.

PMID- 24906695
TI  - Segmental atrophy of the liver: an uncommon and often unrecognized pseudotumor.

PMID- 24906696
TI  - Intraductal radiofrequency ablation for management of malignant biliary
      obstruction.
AB  - Self-expandable metal stents (SEMS) are the current standard of care for the
      palliative management of malignant biliary strictures. Recently, endoscopic
      ablative techniques with direct affect to local tumor have been developed to
      improve SEMS patency. Several reports have demonstrated the technical feasibility
      and safety of intraductal radiofrequency ablation (RFA), by both endoscopic and
      percutaneous approaches, in palliation of malignant strictures of the bile duct.
      Intraductal RFA has also been used in the treatment of occlusion of both covered
      and uncovered SEMS occlusion from tumor ingrowth or overgrowth. This article
      provides a comprehensive review of intraductal RFA in the management of malignant
      biliary obstruction. 

PMID- 24906697
TI  - Gastrointestinal mucormycosis initially manifest as hematochezia from arterio
      enteric fistula.

PMID- 24906698
TI  - When to CHEUS contrast-enhanced endoscopic ultrasound to assess gallbladder wall
      thickening.

PMID- 24906699
TI  - Nutritional approach to the prevention of complications of prematurity with
      emphasis on vitamin A supplementation.

PMID- 24906700
TI  - Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs.
      primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma:
      NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893,
      ISRCTN82191749).
AB  - BACKGROUND: Median OS after surgery in curative intent for non-metastasized
      pancreas cancer ranges under study conditions from 17.9 months to 23.6 months.
      Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or
      both. Observational and autopsy series report local recurrence rates of up to 87%
      even after potentially "curative" R0 resection. To achieve better local control,
      neoadjuvant CRT has been suggested for preoperative tumour downsizing, to elevate
      the likelihood of curative, margin-negative R0 resection and to increase the OS
      rate. However, controlled, randomized trials addressing the impact of neoadjuvant
      CRT survival do not exist. METHODS/DESIGN: The underlying hypothesis of this
      randomized, two-armed, open-label, multicenter, phase III trial is that
      neoadjuvant CRT increases the three-year overall survival by 12% compared to
      patients undergoing upfront surgery for resectable pancreatic cancer. A rigorous,
      standardized technique of histopathologically handling Whipple specimens will be
      applied at all participating centers. Overall, 410 patients (n=205 in each study
      arm) will be enrolled in the trial, taking into regard an expected drop out rate
      of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to
      undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1
      rates, respectively, surgical resectability rate, local and distant disease-free
      and global survival, and first site of tumor recurrence constitute further
      essential endpoints of the trial. DISCUSSION: For the first time, the NEOPA study
      investigates the impact of neoadjuvant CRT on survival of resectable pancreas
      head cancer in a prospectively randomized manner. The results of the study have
      the potential to change substantially the treatment regimen of pancreas cancer.
      TRIAL REGISTRATION: Clinical Trial gov: NCT01900327, DRKS00003893,
      ISRCTN82191749.

PMID- 24906701
TI  - Cortical thinning correlates with cognitive change in multiple sclerosis but not
      in neuromyelitis optica.
AB  - OBJECTIVES: To compare spatial patterns of cortical thickness alterations in
      neuromyelitis optica (NMO) and multiple sclerosis (MS); and to investigate the
      correlations between cortical thinning and clinical variables in NMO and MS.
      METHODS: We studied 23 patients with NMO, 27 patients with MS and 26 healthy
      controls (HCs). The global, brain region and vertex-based cortical thickness
      (CTh) were analysed and compared among the three groups. A general linear model
      was used to investigate the correlations between cortical thinning and clinical
      measures. RESULTS: A limited number of cortical regions in visual cortex were
      found to be significantly thinner in NMO patients than in HCs. The MS patients
      exhibited more widespread cortical thinning compared with HCs, and significantly
      greater cortical thinning in the insula and the parahippocampus compared with
      NMO. The extent of cortical thinning in several brain regions correlated with
      cognitive measures in MS, but not in NMO. CONCLUSIONS: Neocortical thinning in
      NMO mainly affects visual cortex, while MS patients show much more extensive
      cortical thinning. Cognitive changes are correlated with cortical atrophy in MS
      not in NMO. The substrates of cognitive changes in MS and NMO could therefore be
      different. KEY POINTS: MS patients show much more extensive cortical thinning
      than NMO. Cortical thinning of insula and parahippocampus particularly
      distinguishes MS from NMO. Cognitive changes are correlated with cortical atrophy
      in MS but not in NMO.

PMID- 24906702
TI  - Elucidating and tuning the strain-induced non-linear behavior of polymer
      nanocomposites: a detailed molecular dynamics simulation study.
AB  - By setting up a coarse-grained model of polymer nanocomposites, we monitored the
      change in the elastic modulus as a function of the strain, derived from the
      stress-strain behavior by determining uniaxial tension and simple shear of two
      typical spatial distribution states (aggregation and dispersion) of nanoparticles
      (NPs). In both these cases, we observed that the elastic modulus decreases non
      linearly with the increase of strain and reaches a low plateau at larger strains.
      This phenomenon is similar to the so-called "Payne effect" for elastomer
      nanocomposites. Particularly, the modulus of the aggregation case is more
      sensitive to the imposed strain. By examining the structural parameters, such as
      the number of neighboring NPs, coordination number of NPs, root-mean-squared
      average force exerted on the NPs, local strain, chain conformations (bridge,
      dangle, loop, interface bead and connection bead), and the total interaction
      energy of NP-polymer and NP-NP, we inferred that the underlying mechanism of the
      aggregation case is the disintegration of the NP network or clusters formed
      through direct contact; however, for the dispersion case, the non-linear behavior
      is attributed to the destruction of the NP network or clusters formed through the
      bridging of adsorbed polymer segments among the NPs. The former physical network
      is influenced by NP-NP interaction and NP volume fraction, while the latter is
      influenced by NP-polymer interaction and NP volume fraction. Lastly, we found
      that for the dispersion case, further increasing the inter-particle distance or
      grafting NPs with polymer chains can effectively reduce the non-linear behavior
      due to the decrease of the physical network density. In general, this simulation
      work, for the first time, establishes the correlation between the micro
      structural evolution and the strain-induced non-linear behavior of polymer
      nanocomposites, and sheds some light on how to reduce the "Payne effect". 

PMID- 24906704
TI  - A cost-effective, community-based, mosquito-trapping scheme that captures spatial
      and temporal heterogeneities of malaria transmission in rural Zambia.
AB  - BACKGROUND: Monitoring mosquito population dynamics is essential to guide
      selection and evaluation of malaria vector control interventions but is typically
      implemented by mobile, centrally-managed teams who can only visit a limited
      number of locations frequently enough to capture longitudinal trends. Community
      based (CB) mosquito trapping schemes for parallel, continuous monitoring of
      multiple locations are therefore required that are practical, affordable,
      effective, and reliable. METHODS: A CB surveillance scheme, with a monthly
      sampling and reporting cycle for capturing malaria vectors, using Centers for
      Disease Control and Prevention light traps (LT) and Ifakara Tent Traps (ITT),
      were conducted by trained community health workers (CHW) in 14 clusters of
      households immediately surrounding health facilities in rural south-east Zambia.
      At the end of the study, a controlled quality assurance (QA) survey was conducted
      by a centrally supervised expert team using human landing catch (HLC), LT and ITT
      to evaluate accuracy of the CB trapping data. Active surveillance of malaria
      parasite infection rates amongst humans was conducted by CHWs in the same
      clusters to determine the epidemiological relevance of these CB entomological
      surveys. RESULTS: CB-LT and CB-ITT exhibited relative sampling efficiencies of 50
      and 7%, respectively, compared with QA surveys using the same traps. However,
      cost per sampling night was lowest for CB-LT ($13.6), followed closely by CB-ITT
      ($18.0), both of which were far less expensive than any QA survey (HLC: $138, LT:
      $289, ITT: $269). Cost per specimen of Anopheles funestus captured was lowest for
      CB-LT ($5.3), followed by potentially hazardous QA-HLC ($10.5) and then CB-ITT
      ($28.0), all of which were far more cost-effective than QA-LT ($141) and QA-ITT
      ($168). Time-trends of malaria diagnostic positivity (DP) followed those of An.
      funestus density with a one-month lag and the wide range of mean DP across
      clusters was closely associated with mean densities of An. funestus caught by CB
      LT (P < 0.001). CONCLUSIONS: CB trapping schemes appear to be far more
      affordable, epidemiologically relevant and cost-effective than centrally
      supervised trapping schemes and may well be applicable to enhance intervention
      trials and even enable routine programmatic monitoring of vector population
      dynamics on unprecedented national scales.

PMID- 24906703
TI  - Grey matter volumetric changes related to recovery from hand paresis after
      cortical sensorimotor stroke.
AB  - Preclinical studies using animal models have shown that grey matter plasticity in
      both perilesional and distant neural networks contributes to behavioural recovery
      of sensorimotor functions after ischaemic cortical stroke. Whether such
      morphological changes can be detected after human cortical stroke is not yet
      known, but this would be essential to better understand post-stroke brain
      architecture and its impact on recovery. Using serial behavioural and high
      resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of
      dexterous hand function in 28 patients with ischaemic stroke involving the
      primary sensorimotor cortices. We were able to classify three recovery subgroups
      (fast, slow, and poor) using response feature analysis of individual recovery
      curves. To detect areas with significant longitudinal grey matter volume (GMV)
      change, we performed tensor-based morphometry of MRI data acquired in the
      subacute phase, i.e. after the stage compromised by acute oedema and
      inflammation. We found significant GMV expansion in the perilesional premotor
      cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV
      contraction in the contralesional cerebellum. According to an interaction model,
      patients with fast recovery had more perilesional than subcortical expansion,
      whereas the contrary was true for patients with impaired recovery. Also, there
      were significant voxel-wise correlations between motor performance and
      ipsilesional GMV contraction in the posterior parietal lobes and expansion in
      dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated
      with successful recovery after cortical stroke, possibly reflecting the
      restructuring of local cortical networks. Distant changes within the prefrontal
      striato-thalamic network are related to impaired recovery, probably indicating
      higher demands on cognitive control of motor behaviour. 

PMID- 24906705
TI  - Atropine first is safer than conventional atropine administration in older people
      undergoing dobutamine stress echocardiography.
AB  - OBJECTIVE: Early injection of atropine during dobutamine stress echocardiography
      (DSE) has been demonstrated in retrospective analyses to reduce the duration and
      dose of dobutamine infusion, while preserving a similar diagnostic accuracy with
      a lower incidence of adverse effects. This study explores the safety of using
      atropine as a start drug before dobutamine infusion (ADSE protocol) in comparison
      with the conventional protocol (DASE protocol) in older patients undergoing DSE
      for ischemia evaluation. METHODS: One hundred consecutive older patients were
      prospectively enrolled. When eligible, they were randomly assigned to undergo
      either the DASE protocol (group A, 50 patients) or the ADSE protocol (group B, 50
      patients) when atropine (1.0 mg) was first administered 3 min before dobutamine
      infusion followed by 0.5 mg increments (maximum 1.0 mg) thereafter. Patients were
      monitored for adverse drug effects. Test duration was calculated. RESULTS: The
      mean age of the whole study cohort was 67.8+/-4.3 years and 58 (58%) were men.
      Patients in group A had longer test duration (21.8+/-1.3 versus 13.7+/-0.77 min,
      p<0.001) and higher mean dobutamine infusion rate (39+/-8.2 versus 28.2+/-9.5
      MUg/kg/min, p<0.001). The two groups received a similar total dose of atropine.
      Group A patients showed significantly higher incidence of extrasystoles,
      nonsustained ventricular tachycardia and severe hypotension (p<0.05). CONCLUSION:
      In older patients undergoing DSE, using atropine as a start drug, that is,
      adopting the ADSE protocol, is associated with shorter test duration, lower mean
      dobutamine infusion rate and consequently fewer adverse effects.

PMID- 24906708
TI  - Central pontine myelinolysis without electrolyte disorder, alcoholism or
      denutrition.

PMID- 24906707
TI  - Accuracy of the Babinski sign in the identification of pyramidal tract
      dysfunction.
AB  - BACKGROUND: The extensor plantar response described by Joseph Babinski (1896)
      indicates pyramidal tract dysfunction (PTD) but has significant inter-observer
      variability and inconsistent accuracy. The goal of this study was to determine
      the accuracy of the Babinski sign in subjects with verified PTD. METHODS: We
      studied 107 adult hospitalized and outpatient subjects evaluated by neurology.
      The reference standard was the blinded and independent diagnosis of an expert
      neurologist based on anamnesis, physical examination, imaging and complementary
      tests. Two neurologists elicited the Babinski sign in each patient independently,
      blindly and in a standardized manner to measure inter-observer variability; each
      examination was filmed to quantify intra-observer variability. RESULTS: Compared
      with the reference standard, the Babinski sign had low sensitivity (50.8%, 95%CI
      41.5-60.1) but high specificity (99%, 95%CI 97.7-100) in identifying PTD with a
      positive likelihood ratio of 51.8 (95%CI 16.6-161.2) and a calculated inter
      observer variability of 0.73 (95%CI 0.598-0.858). The intraevaluator reliability
      was 0.571 (95%CI 0.270-0.873) and 0.467 (95%, CI 0.019-0.914) respectively, for
      each examiner. CONCLUSION: The presence of the Babinski sign obtained by a
      neurologist provides valid and reliable evidence of PTD; due to its low
      sensitivity, absence of the Babinski sign still requires additional patient
      evaluation if PTD is suspected.

PMID- 24906706
TI  - Substrate and strain alter the muscle-derived mesenchymal stem cell secretome to
      promote myogenesis.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) reside in a variety of tissues and
      provide a stromal role in regulating progenitor cell function. Current studies
      focus on identifying the specific factors in the niche that can alter the MSC
      secretome, ultimately determining the effectiveness and timing of tissue repair.
      The purpose of the present study was to evaluate the extent to which substrate
      and mechanical strain simultaneously regulate MSC quantity, gene expression, and
      secretome. METHODS: MSCs (Sca-1+CD45-) isolated from murine skeletal muscle
      (muscle-derived MSCs, or mMSCs) via fluorescence-activated cell sorting were
      seeded onto laminin (LAM)- or collagen type 1 (COL)-coated membranes and exposed
      to a single bout of mechanical strain (10%, 1 Hz, 5 hours). RESULTS: mMSC
      proliferation was not directly affected by substrate or strain; however, gene
      expression of growth and inflammatory factors and extracellular matrix (ECM)
      proteins was downregulated in mMSCs grown on COL in a manner independent of
      strain. Focal adhesion kinase (FAK) may be involved in substrate regulation of
      mMSC secretome as FAK phosphorylation was significantly elevated 24 hours post
      strain in mMSCs plated on LAM but not COL (P <0.05). Conditioned media (CM) from
      mMSCs exposed to both LAM and strain increased myoblast quantity 5.6-fold 24
      hours post-treatment compared with myoblasts treated with serum-free media (P
      <0.05). This response was delayed in myoblasts treated with CM from mMSCs grown
      on COL. CONCLUSIONS: Here, we demonstrate that exposure to COL, the primary ECM
      component associated with tissue fibrosis, downregulates genes associated with
      growth and inflammation in mMSCs and delays the ability for mMSCs to stimulate
      myoblast proliferation.

PMID- 24906709
TI  - Comment re: Journal of the Neurological Sciences 260 (2007) 132-138, PMID
      17540407.

PMID- 24906710
TI  - The Babinski sign.

PMID- 24906711
TI  - Demyelinating disease and psoriasis: interferon versus dimethyl fumarate.

PMID- 24906712
TI  - Usefulness of the modified F-ratio for assessments of proximal conduction in
      chronic inflammatory demyelinating polyneuropathy superimposed on Charcot Marie
      Tooth disease type 1A.

PMID- 24906713
TI  - Government support for alcohol industry: promoting exports, jeopardising global
      health?

PMID- 24906714
TI  - Can palliative care teams relieve some of the pressure on acute services?

PMID- 24906715
TI  - Why is talking about dying such a challenge?

PMID- 24906716
TI  - What are the four phases of clinical research trials?

PMID- 24906717
TI  - Japanese governor signs agreements with Johns Hopkins and Harvard medical schools
      to open first US medical school in Japan.

PMID- 24906718
TI  - Open letter: European Medicines Agency should remove barriers to access clinical
      trial data.

PMID- 24906719
TI  - Medication regimen complexity in institutionalized elderly people in an aging
      society.
AB  - BACKGROUND: Complex medication regimens may adversely affect compliance and
      treatment outcomes. Complexity can be assessed with the medication regimen
      complexity index (MRCI), which has proved to be a valid, reliable tool, with
      potential uses in both practice and research. OBJECTIVE: To use the MRCI to
      assess medication regimen complexity in institutionalized elderly people.
      SETTING: Five nursing homes in mainland Portugal. METHODS: A descriptive, cross
      sectional study of institutionalized elderly people (n = 415) was performed from
      March to June 2009, including all inpatients aged 65 and over taking at least one
      medication per day. MAIN OUTCOME MEASURE: Medication regimen complexity index.
      RESULTS: The mean age of the sample was 83.9 years (+/-6.6 years), and 60.2 %
      were women. The elderly patients were taking a large number of drugs, with 76.6 %
      taking more than five medications per day. The average medication regimen
      complexity was 18.2 (+/-SD = 9.6), and was higher in the females (p < 0.001). The
      most decisive factors contributing to the complexity were the number of drugs and
      dosage frequency. In regimens with the same number of medications, schedule was
      the most relevant factor in the final score (r = 0.922), followed by
      pharmaceutical forms (r = 0.768) and additional instructions (r = 0.742).
      CONCLUSION: Medication regimen complexity proved to be high. There is certainly
      potential for the pharmacist's intervention to reduce it as part as the
      medication review routine in all the patients.

PMID- 24906721
TI  - Xanthan gum stabilized gold nanoparticles: characterization, biocompatibility,
      stability and cytotoxicity.
AB  - Xanthan gum (XG) has been widely used in food, pharmaceutical and cosmetic
      industries. In the present study, we explored the potential of XG in the
      synthesis of gold nanoparticle. XG was used as both reducing and stabilizing
      agent. The effect of various formulation and process variables such as
      temperature, reaction time, gum concentration, gum volume and gold concentration,
      in GNP preparation was determined. The XG stabilized, rubey-red XGNP were
      obtained with 5 ml of XG aqueous solution (1.5 mg/ml). The optimum temperature
      was 80 degrees C whereas the reaction time was 3 h. The optimized nanoparticles
      were also investigated as drug delivery carrier for doxorubicin hydrochloride.
      DOX loaded gold nanoparticles (DXGP) were characterized by dynamic light
      scattering, TEM, FTIR, and DSC analysis. The synthesized nanoparticle showed mean
      particle size of 15-20 nm and zeta potential -29.1 mV. The colloidal stability of
      DXGP was studied under different conditions of pH, electrolytes and serum.
      Nanoparticles were found to be stable at pH range between pH 5-9 and NaCl
      concentration up to 0.5 M. In serum, nanoparticles showed significant stability
      up to 24h. During toxicity studies, nanoparticles were found biocompatible and
      non-toxic. Compared with free DOX, DXGP displayed 3 times more cytotoxicity in
      A549 cells. In conclusion, this study provided an insight to synthesize GNP
      without using harsh chemicals.

PMID- 24906720
TI  - Gamma knife for functional diseases.

PMID- 24906723
TI  - Synthesis and characterization of graphene oxide/carboxymethylcellulose/alginate
      composite blend films.
AB  - In this work, graphene oxide/carboxymethylcellulose/alginate (GO/CMC/Alg)
      composite blends were prepared by a simple solution mixing-evaporation method.
      The resulting structure, thermal stability, and mechanical properties of the
      blends were investigated by wide-angle X-ray diffractometry, Fourier transform
      infrared spectroscopy, Raman spectroscopy, scanning electron microscopy,
      thermogravimetric analysis, and mechanical testing. The obtained findings
      revealed that CMC, Alg, and graphene oxide were able to form a homogeneous
      mixture. When compared to a CMC/Alg blend, the incorporation of 1 wt% graphene
      oxide improved the tensile strength and Young's modulus by 40% and 1128%,
      respectively. In addition, the GO/CMC/Alg composite blend film showed a higher
      storage modulus than the CMC/Alg blend.

PMID- 24906722
TI  - Optimization for ultrasound-assisted extraction of polysaccharides with
      antioxidant activity in vitro from the aerial root of Ficus microcarpa.
AB  - In this study, optimization of ultrasound-assisted extraction and antioxidant
      activity of polysaccharides from the aerial root of Ficus microcarpa (FMPS) were
      investigated. The optimal conditions for extraction of FMPS were determined as
      followings: ultrasound power 200 W, ultrasound temperature 70 degrees C,
      extraction temperature 74 degrees C, liquid-solid ratio 35, extraction time 238
      min, ultrasound time 49 min. The experimental yield of FMPS (3.44%) obtained
      under these conditions was well agreement with the value predicted by the model.
      In addition, Fourier transform-infrared spectroscopy and antioxidant activity
      assays revealed that FMPS were acidic polysaccharides and had strong Fe2+
      chelating activity and moderate hydrogen peroxide scavenging effect. Further work
      on the purification, structure characterization and antioxidant activity in vivo
      of FMPS is in progress.

PMID- 24906724
TI  - Effect of potassium sorbate on antimicrobial and physical properties of starch
      clay nanocomposite films.
AB  - Using fresh foods which undergo the least processing operations developed widely
      in recent years. Active packaging is a novel method for preserving these
      products. Active starch-clay nanocomposite films which contained potassium
      sorbate (PS) at a level of 0, 5, 7.5 and 10 g PS/100 g starch were produced and
      their physical, mechanical and antimicrobial properties were evaluated. In order
      to evaluate antimicrobial properties of films Aspergillus niger was used. The
      results showed that 5% of the PS did not produce antimicrobial property in the
      film, but by increasing the content of the additive in film formulation,
      antimicrobial effect increased. PS increased water permeability and elongation at
      break of the films, but decreased tensile strength. The rate of PS migration into
      the semi-solid medium in starch-nanocomposites was lower than starch films. This
      shows that nanocomposite films could retain their antimicrobial property for
      longer time.

PMID- 24906725
TI  - The physicochemical property characterization of agar acetate.
AB  - A series of agar acetates with different degree of substitution (DS) were
      prepared, and their properties were determined and analyzed. The results showed
      that the gelling temperature, the gel melting temperature, the gel strength, the
      gel hardness, the gel fracturability, the gel springiness and the solution
      apparent viscosity of agar acetates all decreased except that their gel
      cohesiveness increased with the increase of DS. The variation process of agar
      molecules in solution from coil to helix could be also observed by measuring
      solution optical rotation in a lower concentration at which even the solution
      could not form a gel. The gel skeleton structures of agar acetates were of porous
      network structures, and the pores became smaller and denser with the increase of
      DS. After acetylation, the water holding capacity of the agar was improved, but
      its thermal stability was lowered. 

PMID- 24906726
TI  - Amide-linked N-methacryloyl sucrose containing polymers.
AB  - 1',2,3,3',4,4',6-Hepta-O-benzyl-6'-N-methacryloyl-6'-deoxysucrose 1, 6'-deoxy-6'
      N-methacryloyloxyethylureido sucrose 2 and 6,6'-dideoxy-6,6'-N
      dimethacryloyloxyethylureido sucrose 3 have been homo-polymerized and
      copolymerized with styrene by a free radical process, yielding polymer materials
      with pendant sucrose moieties, attached to the polymer backbone via amide
      linkages. The results demonstrated that varying the structural features of the
      monomers, greatly affected the thermal and rheological properties of the
      polymers. The polymer materials obtained have been characterized by NMR, MALDI
      TOF, DSC, AFM and EWC (equilibrium water content). The efficient synthesis of the
      three novel, regioisomerically pure, N-methacryloylamide sucrose-containing
      monomers (1, 2 and 3) have been described. 

PMID- 24906727
TI  - Cellulose nanofibril based graft conjugated polymer films act as a chemosensor
      for nitroaromatic.
AB  - A cellulose nanofibril film is modified by chemical assembly of boronate
      terminated conjugated polymer chains at its specific sites, C-6 carboxyl groups.
      The modified cellulose nanofibril film is used as a fluorescent sensor for
      nitroaromatic vapor. Thanks to the specific reactive sites, numerous loose
      cavities or pathways located in the film sensor's out-layer have been formed, and
      the fraction of easily accessible cavities of the novel fluorescent film sensor
      is up to 0.97, which could benefit the penetration and diffusion of analyte
      vapor. Therefore, the novel fluorescent film sensor exhibits high sensitivity
      toward nitroaromatic vapor with a fast response. The fluorescence quenching
      efficiency of the chemical-assembly film sensor is about 3 times larger than that
      of the spin-cast film sensor using the same conjugated polymer for 600 s exposure
      to DNT vapor. In addition, the novel fluorescent film sensor shows good
      reversibility.

PMID- 24906728
TI  - Water barrier properties of starch films reinforced with cellulose nanocrystals
      obtained from sugarcane bagasse.
AB  - Water transport in edible films based on hydrophilic materials such as starch, is
      a complex phenomenon due to the strong interaction of sorbed water molecules with
      the polymeric structure. Cellulose nanocrystals (CNC) were obtained from
      sugarcane bagasse. Starch and starch/CNC films were formulated and their water
      barrier properties were studied. The measured film solubility, contact angle, and
      water sorption isotherm indicated that reinforced starch/CNC films have a lower
      affinity to water molecules than starch films. The effects that the driving force
      and the water activity (aw) values at each side of the film have on permeability
      were analyzed. Permeability, diffusivity, and solubility coefficients indicated
      that the permeation process depends mostly on the tortuous pathway formed by the
      incorporation of CNC and therefore were mainly controlled by water diffusion. The
      interaction between CNC and starch chain is favoured by the chemical similarities
      of both molecules. 

PMID- 24906729
TI  - A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta
      glycerophosphate.
AB  - In order to get a water-soluble in situ gel-forming system, a thiolated chitosan,
      chitosan-4-thio-butylamidine (CS-TBA) conjugate was synthesized and used to
      replace the unmodified chitosan in the application of the in situ gel-forming
      system. A novel thermo-sensitive hydrogel was prepared based on CS
      TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (beta-GP). The gel
      formation, rheological properties, morphology, degradation, cytotoxicity, as well
      as protein release process of the novel gel system were investigated in this
      study. The CS-TBA/HA/beta-GP gel showed a higher storage modulus (G') and loss
      modulus (G") and a decreased bovine serum albumin (BSA) release rate which was
      maintained the protein release for a longer time compared with the unmodified
      chitosan (CS)/HA/beta-GP gel, due to the existence of thiol groups and/or
      disulfide bonds. The CS-TBA/HA/beta-GP gel has a porous structure with a uniform
      distribution of nano-hydroxyapatite, an appropriate degradation rate and low
      cytotoxicity, showing potential applications in drug delivery and tissue
      engineering. 

PMID- 24906730
TI  - Characterization of cassava starch based foam blended with plant proteins, kraft
      fiber, and palm oil.
AB  - Cassava starch foam (CSF) trays blended with zein, gluten, soy protein, kraft
      fiber, and palm oil at various concentrations: 0, 5, 10 and 15% by weight of
      starch, were characterized. The addition of zein and gluten into CSF resulted in
      consolidated and homogeneous structural foams compared to its controls. Moreover,
      the flexural and compressive strength increased with increasing kraft, zein and
      gluten. CSF containing 15% kraft gave the highest flexural and compressive
      strength. However, the addition of palm oil into CSF gave the lowest flexural
      strength and compressive strength. The observed water absorption and water
      solubility index of CSFs blended with 15% zein and 15% gluten protein was lowest.
      Although kraft, zein and gluten could improve mechanical properties, water
      absorption and water solubility were greater than the expanded polystyrene foam
      (EPS). The CSF trays in this study might be an alternative for packing low water
      content foods. 

PMID- 24906731
TI  - Synthesis and electrical properties of polyaniline/iota-carrageenan
      biocomposites.
AB  - Polyaniline/iota-carrageenan (iota-CGN) biocomposites were synthesized via in
      situ methodology using ammonium persulfate as the oxidizing agent. Both ionic
      (band at 1131 cm(-1)) and hydrogen bond (bands at 2500 and 3500 cm(-1))
      interactions between polyaniline and iota-CGN were determined by infrared
      spectroscopy. Such intermolecular interactions provided the biocomposites with a
      cross-linked structure that provided the materials with hydrogel behavior.
      Biocomposite electro-conductivity, determined by the 4-probe technique, was in
      the range of semiconductors (10(-3) to 10(-2) S cm(-1)); whereas electro
      activity, assessed by cyclic voltammetry, showed the oxidation-reduction
      transitions typical of polyaniline. Based on the properties of polyaniline and
      iota-CGN, some applications for the new materials in the field of biosensor
      design, electrochemical capacitors, or tissue engineering scaffolds are possible.
      It is worth saying that both electro-conductive and electro-active properties of
      polyaniline/iota-CGN biocomposites are reported here for the first time.

PMID- 24906732
TI  - In situ hydrogel constructed by starch-based nanoparticles via a Schiff base
      reaction.
AB  - Polysaccharide-based hydrogels are remarkable materials for the biomedical fields
      because of its excellent biodegradation and biocompatibility. In this work, a
      novel polysaccharide-based hydrogel was fabricated by in situ crosslinking of
      starch-based nanoparticles and polyvinylamine. Starch was decorated with
      cholesterol group and aldehyde groups. TEM and DLS showed that the cholesterol
      modified oxidation starch (OCS) exhibited a core-shell nanoparticles with mean
      size of ~143 nm in aqueous. The hydrogel was then synthesized via Schiff base
      reaction. Rheological measurements demonstrated the incorporation of cholesterol
      groups not only reduced the gel time but also improved the storage modulus of the
      hydrogel compared with the oxide starch crosslinked hydrogel. SEM showed the OCS
      based hydrogels possess a well-defined porous structure. Furthermore, doxorubicin
      (DOX) was used as model drug to investigate the control and release properties of
      OCS hydrogels. This OCS hydrogel would be a promising drug carrier for biomedical
      applications.

PMID- 24906733
TI  - Injectable hyaluronic acid hydrogel for 19F magnetic resonance imaging.
AB  - We report on a 19F labeled injectable hyaluronic acid (HA) hydrogel that can be
      monitored by both 1H and 19F MR imaging. The HA based hydrogel formed via
      carbazone reaction can be obtained within a minute by simple mixing of HA
      carbazate and HA-aldehyde derivatized polymers. 19F contrast agent was linked to
      with carbazate and thiol dually functionalized HA via orthogonal Michael addition
      reaction which afforded cross-linkable and 19F labeled HA. The 19F labeling of HA
      polymer did not affect the mechanical properties of the formed hydrogel. As a
      result, the shape of a hydrogel sample could be imaged very well by both 1H MRI
      and high resolution 19F MRI. This hydrogel has high potential in clinical
      applications since it is injectable, biocompatible, and can be tracked in a
      minimally invasive manner. The present approach can be applied in preparation of
      injectable 19F labeled hydrogel biomaterials from other natural
      biomacromolecules.

PMID- 24906734
TI  - Lyase-catalyzed degradation of alginate in the gelled state: effect of gelling
      ions and lyase specificity.
AB  - Lyase-catalyzed degradation has been proposed as a more cell-friendly alternative
      to dissolution of alginate gels than using chelating agents. In this study, we
      investigated the effect of lyase specificity on degradation of alginate gels,
      including the effect of crosslinking ions with different affinity for the
      polymer. Degradation kinetics and products were analyzed. In particular, the
      degradation products were characterized using novel methods for alginate sequence
      determination by chromatography. Lyase-catalyzed gel disruption worked well for
      gels crosslinked with calcium, but was less effective when barium was included in
      the gel formulation. The importance of crosslinking of long G-blocks in
      maintaining the structural integrity of the gels was identified. The failure to
      degrade these long G-blocks, either due to protection of the G-blocks by strong
      ionic crosslinking or due to lack of lyase activity on G-G linkages, resulted in
      retained resistance to mechanical disruption of the gel. 

PMID- 24906735
TI  - Factors affecting inulin crystallization after its complete dissolution.
AB  - In this study, we analyzed inulin crystallization during one year after its
      complete dissolution and an effect of inulin crystal seeds concentration on
      rheological and textural properties of inulin gels. 20% and 25% solutions of
      three different inulins, one native and two high performance (crystal and
      amorphous), were prepared by heating at 100 degrees C for 5 min. During one year
      of storage at 20 degrees C, inulin did not form a gel structure, but only
      precipitates and a crystal layer on the walls of the containers. Addition of
      crystal seeds (0.02-2%) caused formation of gel structure. Minimal concentration
      of the crystal seeds necessary to form a strong inulin gel was 0.4%.
      Crystallographic structure of inulin powder did not have an influence on the
      formed gels. The obtained results allow inulin gelation to control which can be
      crucial in novel foods, the structure of which is based on inulin.

PMID- 24906736
TI  - Preparation and characterization of double crosslinked hydrogel films from
      carboxymethylchitosan and carboxymethylcellulose.
AB  - A novel crosslinked hydrogel film was prepared from carboxymethylchitosan (CMCS)
      and carboxymethylcellulose (CMC) by ionical and covalent crosslinking with CaSO4
      and genipin, respectively. The swelling ratio of the crosslinked CMCS/CMC
      hydrogel films was investigated at different pH solutions (1-9), and the results
      indicated that the crosslinked hydrogels had the swelling-deswelling properties
      with two primary peaks of swelling ratio at pH 3 and 7. The surface morphologies
      of the crosslinked hydrogels at different pH values provided evidences of the
      swelling-deswelling properties. The mechanical properties of the hydrogel films
      were also examined. The ionical and covalent crosslinking were found to have the
      primary impact on the toughness and max load, respectively, of the crosslinked
      hydrogels. The cells comparatively cultured on the crosslinked hydrogels and the
      negative and positive controls suggested the biocompatibility of the crosslinked
      CMCS/CMC films. This kind of hydrogel films have potential application in drug
      delivery vehicles and skin tissue engineering. 

PMID- 24906737
TI  - Study on novel functional materials carboxymethyl cellulose lithium (CMC-Li)
      improve high-performance lithium-ion battery.
AB  - Novel cellulose derivative CMC-Li was synthesized by cotton as raw material. The
      mechanism of the CMC-Li modified electrode materials by electrospinning was
      reported. CMC-Li/lithium iron phosphate (LiFePO4, LFP) composite fiber coated
      with LFP and CMC-Li nanofibers was successfully obtained by electrospinning.
      Then, CMC-Li/LFP nano-composite fiber was carbonized under nitrogen at a high
      temperature formed CNF/LFP/Li (CLL) composite nanofibers as cathode material. It
      can increase the contents of Li+, and improving the diffusion efficiency and
      specific capacity. The battery with CLL as cathode material retained close to
      100% of initial reversible capacity after 200 cycles at 168 mAh g(-1), which was
      nearly the theoretical specific capacity of LFP. The cyclic voltammetry (CV),
      electrochemical impedance spectroscopy (EIS), X-ray diffraction (XRD) and
      scanning electron microscope (SEM) were characterizing material performance. The
      batteries have good electrochemical property, outstanding pollution-free,
      excellent stability.

PMID- 24906738
TI  - Effect of dry heat treatment on the physicochemical properties and structure of
      proso millet flour and starch.
AB  - Proso millet (Panicum miliaceum L.) flour and starch were heated in a dry state
      at 130 degrees C for 2 or 4 h. The effects of dry heat treatment (DHT) on the
      pasting, morphological and structural properties of the samples were evaluated.
      Dry heat treatment had a more significant effect on the pasting viscosity of
      flour than starch; it increased the pasting viscosity of the flour while it only
      increased the final viscosity of the starch. After dry heating, the onset of
      gelatinization and the peak temperatures of the samples increased significantly
      while the endothermic enthalpy decreased. Scanning electron microscopy showed
      that the gel structure of the samples became more compact and the particles were
      plumper when compared with the native ones. Crystallinity of the samples
      decreased while the X-ray diffraction patterns remained the same after DHT.

PMID- 24906739
TI  - Construction of serum resistant micelles based on heparosan for targeted cancer
      therapy.
AB  - A novel micelle based on heparosan and deoxycholic acid (DOCA) conjugate (HD) as
      drug carrier was reported here. As the surface was negatively charged, this
      micelle could resist serum adsorption, showing favorable stability. Moreover,
      fluorescence observation confirmed that it was able to deliver model hydrophobic
      drug doxorubicin (DOX) into HeLa cells efficiently. The DOX-loaded micelles
      showed sustained release behavior at pH 7.4, and accelerated release behavior at
      pH 5.0 or in the presence of beta-glucuronidase, which over-expressed in tumor
      cells. In vitro cytotoxicity assay demonstrated that the half-maximal inhibitory
      concentration (IC50) of DOX-loaded micelles against HeLa cells was much lower
      than that of COS7 cells, showing significant therapeutic distinction between
      tumor cells and normal cells. Combining with the good biocompatibility and
      biodegradability of heparosan, this micelle may be promising in clinical
      application for targeted drug delivery. 

PMID- 24906740
TI  - A glucan isolated from flowers of Lonicera japonica Thunb. inhibits aggregation
      and neurotoxicity of Abeta42.
AB  - Inhibition of Abeta aggregation and attenuation of its cytotoxicity are
      considered to valuable therapeutics for Alzheimer's disease (AD). Here, a glucan
      named as LJW0F2 was purified from flowers of Lonicera japonica Thunb. Using
      monosaccharides composition analysis, methylation analysis, IR and NMR
      spectroscopy, this polysaccharide was elucidated to be an alpha-D-(1->4)-glucan
      with an alpha-(1->4) linked branch attached to the C-6 position. Its inhibitory
      effect on Abeta42 aggregation was measured by fluorescence spectroscopic analysis
      with thioflavine T (ThT) and atomic force microscopy (AFM). We showed that
      polysaccharide LJW0F2 could inhibit Abeta42 aggregation in a dose-dependent
      manner. Besides, LJW0F2 could attenuate the cytotoxicity induced by Abeta42
      aggregation in SH-SY5Y neuroblastoma cells. To the best of our knowledge, this
      was the first report that the exogenous plant-derived polysaccharide might block
      Abeta42 aggregation directly and reduce its toxicity in SH-SY5Y cells.

PMID- 24906741
TI  - Production of antibacterial colored viscose fibers using in situ prepared
      spherical Ag nanoparticles.
AB  - In situ incorporation technique was used for coloration and acquiring excellent
      antibacterial properties for viscose fibers by silver nanoparticles (AgNPs).
      AgNPs were prepared in situ and incorporated in viscose matrix directly without
      using any other reducing and stabilizing agents. The main objective of this
      research was to successfully employ the reducing and stabilizing features of
      cellulose to produce nanosilver-viscose composites. Coloration of fibers after in
      situ AgNPs incorporation is related to surface plasmon resonance of silver.
      Colorimetric data were recorded as a function of washings to characterize the
      final colored fibers. Fastness properties and silver release were all measured to
      study the washable and wear off properties. Depending on the silver
      concentration, yellowish colored fibers with different shades were produced. Good
      fastness properties were obtained after 20 washings without using any crosslinker
      or binder. The colored fibers had excellent antibacterial activities against
      Escherichia coli, even after 20 washings. 

PMID- 24906742
TI  - Impact of ghosts on the viscoelastic response of gelatinized corn starch
      dispersions subjected to small strain deformations.
AB  - Corn starch dispersions (5.0% w/w) were gelatinized by heating at 90 degrees C
      for 20 min using gentle stirring. Under these conditions, ghosts, which are
      insoluble material with high amylopectin content, were detected by optical
      microscopy. Strain sweep tests showed that the gelatinized starch dispersions
      (GSD) exhibited a loss modulus (G") overshoot at relatively low strains (~1%). In
      order to achieve a greater understanding as to the mechanisms giving rise to this
      uncharacteristic nonlinear response at low strains, very small constant torques
      (from 0.05 to 0.5 MUN m) were applied in the bulk of the GSD with a rotating
      biconical disc. This resulted in small deformations exhibiting torque-dependent
      inertio-elastic damped oscillations which were subjected to phenomenological
      modelling. Inertial effects played an important role in the starch mechanical
      response. The model parameters varied with the magnitude of constant small
      applied torque and could be related to microstructural changes of ghosts and to
      the viscoelastic response of GSD.

PMID- 24906743
TI  - Modification of nanofibrillated cellulose using amphiphilic block-structured
      galactoglucomannans.
AB  - Nanofibrillated cellulose (NFC) and hemicelluloses have shown to be highly
      promising renewable components both as barrier materials and in novel
      biocomposites. However, the hydrophilic nature of these materials restricts their
      use in some applications. In this work, the usability of modified O-acetyl
      galactoglucomannan (GGM) for modification of NFC surface properties was studied.
      Four GGM-block-structured, amphiphilic derivatives were synthesized using either
      fatty acids or polydimethylsiloxane as hydrophobic tails. The adsorption of these
      GGM derivatives was consecutively examined in aqueous solution using a quartz
      crystal microbalance with dissipation monitoring (QCM-D). It was found that the
      hydrophobic tails did not hinder adsorption of the GGM derivatives to cellulose,
      which was concluded to be due to the presence of the native GGM-block with high
      affinity to cellulose. The layer properties of the adsorbed block-co-polymers
      were discussed and evaluated. Self-standing NFC films were further prepared and
      coated with the GGM derivatives and the effect of the surface modification on
      wetting properties and oxygen permeability (OP) of the modified films was
      assessed. 

PMID- 24906744
TI  - Characterization and cytocompatibility of an antibiotic/chitosan/cyclodextrins
      nanocoating on titanium implants.
AB  - A novel ciprofloxacin loaded chitosan nanoparticle-based coating onto titanium
      substrates has been developed and characterized to obtain an orthopaedic implant
      surface able to in situ release the antibiotic for the prevention of post
      operative infections. Ciprofloxacin loaded chitosan nanoparticles were obtained
      using the combination of sulfobutyl ether-beta-cyclodextrin and gamma
      cyclodextrin. The resulting nanoparticulate system was characterized by TEM, HPLC
      and XPS. Particle size was in the range 426-552 nm and zeta potential values were
      around +30 mV. This antibacterial coating was able to in vitro inhibit two
      nosocomial Staphylococcus aureus strains growth, with a reduction of about 20
      times compared to controls. No impairment in MG63 osteoblast-like cells
      viability, adhesion and gene expression were detected at 48 h, 7 and 14 days of
      culture. Overall, the investigated coating represents a promising candidate for
      the development of a new antibiotic carrier for titanium implants.

PMID- 24906745
TI  - Gamma irradiation induced modification of bean polysaccharides: impact on
      physicochemical, morphological and antioxidant properties.
AB  - In the present study starches from four bean varieties viz. red, yellow, black
      and white, were gamma irradiated in the dose range of 5-25 kGy to investigate the
      effect of radiation processing on physicochemical, morphological and antioxidant
      properties. Studies revealed positive correlation between gamma irradiation and
      solubility (r=0.91), irradiation and water absorption capacity (r=0.82) and
      negative correlations between irradiation and swelling power (r=-0.92),
      irradiation and pasting properties (r=-0.91) and irradiation and thermal
      properties (r=-0.89). Microscopic observation under scanning electron microscope
      indicated the development of surface cracking and fractures on the surface of
      starch granules with increase in dose. X-ray diffractometry revealed no
      significant change in diffraction patterns between control and irradiated
      starches, except a decrease in relative crystallinity. Irradiation increased the
      proportions of both rapidly digestible starch and enzyme resistant starch of bean
      starches and significantly prevented the retrogradation of bean starches during
      storage. Results of the DPPH radical scavenging activity and ferric reducing
      power indicated significant (p<=0.05) increase in antioxidant activity of all
      irradiated bean starches with increase in dose.

PMID- 24906746
TI  - Green synthesis of chondroitin sulfate-capped silver nanoparticles:
      characterization and surface modification.
AB  - A one-step route for the green synthesis of highly stable and nanosized silver
      metal particles with narrow distribution is reported. In this environmentally
      friendly synthetic method, silver nitrate was used as silver precursor and
      biocompatible chondroitin sulfate (ChS) was used as both reducing agent and
      stabilizing agent. The reaction was carried out in a stirring aqueous medium at
      the room temperature without any assisted by microwave, autoclave, laser
      irradiation, gamma-ray irradiation or UV irradiation. The transparent colorless
      solution was converted to the characteristics light red then deep red-brown color
      as the reaction proceeds, indicating the formation of silver nanoparticles (Ag
      NPs). The Ag NPs were characterized by UV-visible spectroscopy (UV-vis), photon
      correlation spectroscopy, laser Doppler anemometry, transmission electron
      microscopy (TEM), and Fourier-transform infrared spectroscopy (FT-IR). The
      results demonstrated that the obtained metallic nanoparticles were Ag NPs capped
      with ChS. In this report, dynamic light scattering (DLS) was used as a routinely
      analytical tool for measuring size and distribution in a liquid environment. The
      effects of the reaction time, reaction temperature, concentration and the weight
      ratio of ChS/Ag+ on the particle size and zeta potential were investigated. The
      TEM image clearly shows the morphology of the well-dispersed ChS-capped Ag NPs
      are spherical in shape, and the average size (<20 nm) is much smaller than the Z
      average value (76.7 nm) measured by DLS. Meanwhile, the ChS-capped Ag NPs coated
      with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) were
      prepared by an ionic gelation method and the surface charge of Ag NPs was
      switched from negative to positive.

PMID- 24906747
TI  - Increasing viscosity and yields of bacterial exopolysaccharides by repeatedly
      exposing strains to ampicillin.
AB  - A universal method to enhance productivity and viscosity of bacterial
      exopolysaccharides was developed. The technique was based on the principle that
      ampicillin can inhibit the biosynthesis of peptidoglycan, which shares a common
      synthetic pathway with that of bacterial exopolysaccharides. Serial passages of
      three typical representatives of bacterial EPS-producing strains, namely
      Sphingomonas elodea, Xanthomonas campestris, and Paenibacillus elgii, were
      subjected to ampicillin, which was used as a stressor and a mutagen. These mutant
      strains are advantageous over other strains because of two major factors. First,
      all of the resulting strains were almost mutants with increase in EPS
      productivity and viscosity. Second, isolated serial strains showed different
      levels of increase in EPS production and viscosity to satisfy the different
      requirements of practical applications. No differences were observed in the
      monosaccharide composition produced by the mutant and parent strains; however,
      high-viscosity mutant strains exhibited higher molecular weights. The results
      confirmed that the developed method is a controlled universal one that can
      improve exopolysaccharides productivity and viscosity. 

PMID- 24906748
TI  - Micelle-like association of polysaccharides with hydrophobic end groups.
AB  - New dextran derivatives with hydrophobic end groups were synthesized by reductive
      amination of dextran chain ends, followed by chemical modification of the dextran
      main chain by attachment of cationic groups and/or by crosslinking. Properties of
      the aggregates formed by hydrophobic association of the end groups were studied
      by fluorescence, dynamic light scattering, atomic force microscopy and
      transmission electron microscopy and depended on the length of the dextran chain
      (6, 10, 25 kDa) and the hydrophobicity of the end group (alkyl, dialkyl, bile
      acid). All neutral derivatives were able to form micelle-like aggregates above a
      critical aggregation concentration (0.008-0.159 g/dL). Polarity of the micelle
      hydrophobic core was close to or lower than that of neutral low molecular
      surfactants (polarity parameter I1/I3~0.8-1.13), aggregation number was 20-30 and
      hydrodynamic radius 20-30 nm. Attachment of cationic groups to the dextran main
      chain increased critical aggregation concentration and core polarity, but
      cationic polymeric surfactants with good association ability could be obtained by
      an appropriate choice of the content and hydrophobicity of the cationic groups.
      Cross-linking of the micelle shell with divinylsulfone increased micelle
      stability to dilution.

PMID- 24906749
TI  - Preparation and characterization of carboxymethyl derivatives of yeast mannans in
      aqueous solutions.
AB  - Novel carboxymethyl derivatives of yeast mannans of different degrees of
      substitution (DS) were prepared by optimized reaction of concentrated
      polysaccharides in alkaline aqueous solution. Mannans from various yeasts
      differing in size and degree of branching show similar reactivity. Strong
      alkaline conditions during carboxymethylation caused degradation of the
      polysaccharides. The degree of substitution (DS) of Candida albicans mannan and
      dextran were proportional to the amount of monochloroacetate added. However,
      degrees of carboxymethylation of Candida albicans mannan (0.30, 0.41, 0.73) were
      lower than those of dextran (DS=0.33, 0.6, 1.1) using the same amounts of
      monochloroacetate. Evidently the resulted polyanionic derivatives have higher
      hydrodynamic sizes than the original polysaccharides. Non-uniform, variable
      position of substitutions results to non-proportional change of optical rotation
      and increase of complexity of NMR spectra. Basic physico-chemical characteristics
      of novel carboxymethyl mannans obtained by potentiometric titration, FT-IR, UV,
      HPLC, 1H NMR and optical rotation measurements are presented here.

PMID- 24906750
TI  - Polyelectrolytic aqueous guar gum for adsorptive separation of soluble Pb(II)
      from contaminated water.
AB  - The article introduces the concept of homophase adsorption of soluble Pb(II) from
      contaminated water using aqueous guar gum (GG). The process appears to be
      extremely handy since it avoids hectic sample preparation and adsorbent recovery
      stages. The results show that, addition of only 1000 ppm GG removes 56.72% of the
      contaminated Pb(II) within 150 min at 303 K. The best working pH has been found
      to be at 4.5. At this point GG molecules show greatest balance between negative
      zeta potential and high molecular size. Mechanistically, the adsorption follows
      Langmuir model since on formation of a monolayer, the positive Pb(II) prevent
      subsequent adsorption through strong electrostatic repulsion. The adsorption
      kinetics follows pseudo second order model. Both kinetics and thermodynamics of
      the process complies with the conventional hetero facial adsorption models
      despite huge procedural differences.

PMID- 24906751
TI  - Preparation, characterization, and anti-Helicobacter pylori activity of Bi3+
      Hericium erinaceus polysaccharide complex.
AB  - Two new Bi3+-Hericium erinaceus polysaccharide (BiHEP) complexes were prepared
      using Bi3+ and two purified polysaccharides from H. erinaceus (HEPs),
      respectively. The complexes were characterized by elemental analysis, FT-IR, CD,
      SEM, AFM, XRD, and TG. The anti-Helicobacter pylori (Hp) activities in vitro by
      agar dilution assay of the complexes were evaluated. The molecular weights of
      HEPs were 197 and 20 kDa, respectively. All the analyses confirmed the formation
      of new BiHEP complexes with lower content of Bi3+ compared with colloidal bismuth
      subcitrate (CBS), the most utilized bismuth preparation clinically. Furthermore,
      HEPs themselves have definite inhibition effects on Hp, and BiHEP complexes have
      lower content of Bi exhibited strong inhibition effects on Hp (MIC=20 MUg/mL),
      similar to that of CBS with higher content of Bi. The study provides a basis for
      further development of multiple treatments of Hp infection or new medicines.

PMID- 24906753
TI  - Recycling of cell culture and efficient release of intracellular
      fructosyltransferase by ultrasonication for the production of
      fructooligosaccharides.
AB  - Production of fructooligosaccharide (FOS) through efficient cultivation of
      biotransformation process by fructosyltransferase (FTase) was evaluated by two
      new isolates, Aspergillus niger and Aspergillus flavus NFCCI 2364. The saccharide
      consumption revealed lag phase of A. niger in 10 h which were smaller extent than
      A. flavus of 14 h. For the recycling of cell culture, the pellet cells were
      continuously reused after 24 h of submerged fermentation by these microorganisms
      in which FTase activity remains stable in four consecutive cycles in A. niger and
      six cycles in A. flavus. When freshly prepared pellets were sonicated for
      efficient release of intracellular FTase, the best transformation reaction was
      performed at 20 W acoustic power giving conversion yield of FOS 61.43% (w/w) by
      A. niger and 70.44% (w/w) by A. flavus respectively. This study was shown that
      the two fungal isolates can serve as veritable source of intracellular FTase for
      industrial production of FOS.

PMID- 24906752
TI  - Porous silicon-cyclodextrin based polymer composites for drug delivery
      applications.
AB  - One of the main applications of porous silicon (PSi) in biomedicine is drug
      release, either as a single material or as a part of a composite. PSi composites
      are attractive candidates for drug delivery systems because they can display new
      chemical and physical characteristics, which are not exhibited by the individual
      constituents alone. Since cyclodextrin-based polymers have been proven efficient
      materials for drug delivery, in this work beta-cyclodextrin-citric acid in-situ
      polymerization was used to functionalize two kinds of PSi (nanoporous and
      macroporous). The synthesized composites were characterized by microscopy
      techniques (SEM and AFM), physicochemical methods (ATR-FTIR, XPS, water contact
      angle, TGA and TBO titration) and a preliminary biological assay was performed.
      Both systems were tested as drug delivery platforms with two different model
      drugs, namely, ciprofloxacin (an antibiotic) and prednisolone (an anti
      inflammatory), in two different media: pure water and PBS solution. Results show
      that both kinds of PSi/beta-cyclodextrin-citric acid polymer composites, nano-
      and macro-, provide enhanced release control for drug delivery applications than
      non-functionalized PSi samples. 

PMID- 24906754
TI  - Characterization of Raoultella planticola Rs-2 microcapsule prepared with a blend
      of alginate and starch and its release behavior.
AB  - To judiciously use Raoultella planticola Rs-2 and develop its biodegradable and
      controlled-release formulations, Rs-2 was encapsulated with various combinations
      of sodium alginate (NaAlg) and starch. Sodium alginate, soluble starch, and CaCl2
      showed good biocompatibility with Rs-2 for preparing microcapsules. These
      microcapsules were spherical in shape and their particle size, embedding rate,
      swelling ratio of Rs-2 microcapsules and release numbers of viable Rs-2 cells
      increased with the increasing of starch and NaAlg concentrations. Meanwhile, the
      biodegradability of the microcapsules constantly increases when the wt% of starch
      increased, but decreased when the amount of NaAlg increased. In addition, the
      release mechanism of microcapsules was consistent with that of the Ritger-Peppas
      model, which involves the Case II diffusion mechanism. In summary, the desired
      properties of the microcapsules can be modulated by varying the starch and
      alginate amounts of capsule materials. This process has broad application
      prospects to meet the needs of agricultural production. 

PMID- 24906755
TI  - Cationic methylcellulose derivative with serum-compatibility and endosome
      buffering ability for gene delivery systems.
AB  - In this work, methylcellulose was employed as a template polymer with graft of
      polyethylenimine 0.8 kDa (PEI0.8k) for gene delivery systems. Synthesized PEI
      grafted oxidized methylcellulose (MC-PEI) could condense pDNA into positively
      charged and nano-sized particles, which could protect pDNA from serum nuclease.
      The cytotoxicity of MC-PEI was minimal in both serum-free and serum condition due
      to the biocompatibility of methylcellulose and low cytotoxicity of PEI0.8k. MC
      PEI polyplex also showed low cytotoxicity in serum condition. In serum condition,
      MC-PEI showed less decreased transfection efficiency than PEI25k, meaning good
      serum-compatibility of MC-PEI. Bafilomycin A1-treated transfection results
      indicate that the transfection of MC-PEI is mediated via endosomal escape by
      endosome buffering ability. Flow cytometry results suggest that MC-PEI polyplex
      could be internalized into cells and efficiently deliver pDNA to cells due to its
      serum-compatibility. These results demonstrate that MC-PEI possesses a potential
      for efficient gene delivery systems.

PMID- 24906756
TI  - Response surface optimization of ultrasound-assisted enzymatic extraction
      polysaccharides from Lycium barbarum.
AB  - In this study, an efficient ultrasound-assisted enzymatic extraction procedure
      for the water-soluble polysaccharides from the fruit of Lycium barbarum was
      investigated and optimized. Response surface methodology (RSM) based on a three
      level four-factor Box Behnken Design (BBD) was employed to optimize the
      extraction conditions inlcluding extraction time, ultrasonic output power,
      cellulose concentration and extraction temperature. The experimental data were
      adequately fitted into a second-order polynomial model. The optimized conditions
      were as follows: extraction time 20.29 min, ultrasonic output power 78.6 W,
      cellulose concentration 2.15%, extraction temperature 55.79 degrees C. Under
      these conditions, the experimental yield of polysaccharides was 6.31+/-0.03%,
      which matched with the predictive yield of 6.32% well.

PMID- 24906757
TI  - Graft [partially carboxymethylated guar gum-g-poly N-(hydroxymethyl) acrylamide]
      copolymer: from synthesis to applications.
AB  - Graft copolymer of N-(hydroxymethyl) acrylamide with carboxymethylated guar gum
      was synthesized and the reaction conditions were optimized for better yield using
      potassium peroxymonosulfate and thiourea as a redox initiator. The optimum
      reaction conditions for grafting have also been determined by studying the effect
      of N-(hydroxymethyl) acrylamide, hydrogen ion, peroxymonosulphate, thiourea
      concentration and carboxymethylated guar gum along with time and temperature.
      Experimental results show that maximum grafting has been obtained at 1.4 g dm(-3)
      concentration of carboxymethylated guar gum and 16*10(-2) mol dm(-3)
      concentration of N-(hydroxymethyl) acrylamide. It has been observed that grafting
      ratio, add on, conversion, efficiency and rate of grafting increase up to 6.0*10(
      3) mol dm(-3) of hydrogen ion, 2.4*10(-3) mol dm(-3) of thiourea, 14*10(-3) mol
      dm(-3) of peroxymonosulphate and 35 degrees C of temperature. Grafted copolymer
      has been characterized by FTIR spectroscopy and thermogravimetric analysis. Water
      swelling, flocculating, and metal ion uptake properties of partially
      carboxymethylated guar gum-g-N-(hydroxymethyl) acrylamide have been determined.

PMID- 24906758
TI  - Rheological behaviors of cellulose in 1-ethyl-3-methylimidazolium
      chloride/dimethylsulfoxide.
AB  - Dynamic rheological behaviors of alpha-cellulose 1-ethyl-3-methylimidazolium
      chloride ([Emim]Cl)/dimethylsulfoxide (DMSO) solutions were investigated in a
      large range of cellulose concentrations (0.1-10 wt%) at 25 degrees C. The overlap
      concentration c* and the entanglement concentration ce for cellulose in
      [Emim]Cl/DMSO were determined to be 0.5 wt% and 2.0 wt% respectively, and the
      exponents of the specific viscosity etasp versus cellulose concentration c were
      determined as 1.1, 2.1 and 4.7 for dilute, semidilute unentangled and entangled
      regimes respectively, which were in accordance with the scaling prediction for
      neutral polymer in theta solvent. Under the same cellulose concentration, the
      complex viscosity eta*, the reptation time taurep and the relaxation time of a
      segment between entanglements taue all decreased with increasing DMSO content in
      the solvent, while the number of entanglements of cellulose chains and the molar
      mass of an entanglement strand Me both remained unchanged.

PMID- 24906759
TI  - Using carboxylated nanocrystalline cellulose as an additive in cellulosic paper
      and poly (vinyl alcohol) fiber paper.
AB  - Specialty paper (e.g. cigarette paper and battery diaphragm paper) requires
      extremely high strength properties. The addition of strength agents plays an
      important role in increasing strength properties of paper. Nanocrystalline
      cellulose (NCC), or cellulose whiskers, has the potential to enhance the strength
      properties of paper via improving inter-fibers bonding. This paper was to
      determine the potential of using carboxylated nanocrystalline cellulose (CNCC) to
      improve the strength properties of paper made of cellulosic fiber or poly (vinyl
      alcohol) (PVA) fiber. The results indicated that the addition of CNCC can
      effectively improve the strength properties. At a CNCC dosage of 0.7%, the tear
      index and tensile index of the cellulosic paper reached the maximum of 12.8 mN
      m2/g and 100.7 Nm/g, respectively. More importantly, when increasing the CNCC
      dosage from 0.1 to 1.0%, the tear index and tensile index of PVA fiber paper were
      increased by 67.29%, 22.55%, respectively.

PMID- 24906760
TI  - In situ synthesis of MnO2 coated cellulose nanofibers hybrid for effective
      removal of methylene blue.
AB  - A one-step and energy-efficient synthetic method was developed to fabricate
      manganese dioxide (MnO2)/cellulose nanofibers (CNFs) hybrid. In this process,
      bamboo CNFs acted as both a reducing reagent for the Mn (VII) and an ultralight
      support for the generated MnO2 nanosheets. Neither additional reducing reagents
      nor heating were adopted during the synthesis process. The phase constitutions,
      crystal structure and morphology of the hybrid were systematically investigated.
      Both oxidative and adsorptive decolorization of methylene blue (MB) were
      investigated to evaluate its efficiency on dye wastewater treatment. The results
      showed that the few-layer MnO2 nanosheets deposited on CNFs exhibited high
      decolorization efficiency for the oxidation and adsorption of MB. When slurry
      containing 25 mg MnO2/CNFs hybrid was dispersed in 25 mL 80 mg L(-1) MB solution,
      the removal of MB was more than 99.8% within 2 min.

PMID- 24906761
TI  - Influence of plasticiser on the barrier, mechanical and grease resistance
      properties of alginate cast films.
AB  - Alginate cast films were plasticised by two plasticisers--glycerol and sorbitol-
      in different concentrations. As a function of the plasticiser type and
      concentration, the following parameters were investigated: equilibrium moisture
      content (EMC), colour measurement, microscopic analysis by SEM, grease
      resistance, oxygen permeability (OP), water vapour transmission rate (WVTR) and
      the mechanical properties. Both plasticisers have a positive influence on the
      mechanical properties but differ in their effect on the barrier properties.
      Whilst an increasing concentration of glycerol increases the permeability of
      alginate films to oxygen and water vapour, sorbitol did not influence the barrier
      properties to oxygen or water vapour. The behaviour of glycerol is in accordance
      with the free volume theory. The effect of sorbitol is assumed to be due to the
      good steric fit of sorbitol into the alginate network. The good embedding of
      sorbitol between the alginate polymer chains means it can lower the
      intermolecular bonding while still offering bonding possibilities. Therefore the
      flexibility of the cast films is increased while maintaining the barrier
      properties.

PMID- 24906762
TI  - Modified pullulan nanoparticles for oral delivery of lopinavir: formulation and
      pharmacokinetic evaluation.
AB  - In this investigation, we report the use of the pullulan acetate, a hydrophobic
      derivative of pullulan in the formulation of Lopinavir loaded nanoparticles meant
      for oral delivery. Pullulan was modified to pullulan acetate by acetylation
      process in the presence of pyridine; acetylation was confirmed by FT-IR and NMR
      spectra. Lopinavir, an HIV-protease inhibitor was formulated into nanoparticles
      of pullulan acetate by the well-known emulsion-solvent-evaporation method. The
      nanoparticles were tested for particle size, entrapment efficiency, in-vitro drug
      release and stability. Further, extensive pharmacokinetic and tissue distribution
      studies were performed in Wistar rats. The results showed that, with our method,
      we could obtain nanoparticles of ~197 nm, high entrapment efficiency (~75%) and
      monodisperse nature (PDI<0.2). Stability data showed that the nanoparticles were
      stable over a period of 3 months. From the pharmacokinetic study data, we found
      that the relative bioavailability of Lopinavir from nanoparticles was ~2 folds
      higher than the free drug. Moreover, the tissue distribution study showed a
      higher distribution of Lopinavir loaded nanoparticles to lymphoid organs (liver,
      spleen and lymph nodes that are also important viral reservoirs in HIV
      infection). Thus, we conclude that Lopinavir loaded nanoparticle could be a
      superior alternative approach to free Lopinavir in treating HIV infection.

PMID- 24906763
TI  - Development of a myricetin/hydroxypropyl-beta-cyclodextrin inclusion complex:
      preparation, characterization, and evaluation.
AB  - Myricetin shows low oral bioavailability (<10%) in rats due to poor aqueous
      solubility, though it has various pharmacological activities. Complexation with
      cyclodextrins (CDs) is a potent pharmaceutical method to enhance the
      bioavailability of poorly soluble compounds. The myricetin/HP-beta-CD inclusion
      complex was prepared and confirmed by DSC, PXRD, and SEM. Here, the inclusion
      mode is described in detail with regard to structural and energetic aspects using
      a phase solubility diagram and 1H NMR, NOESY, and FT-IR spectra. The water
      solubility and dissolution rate of myricetin were greatly enhanced by forming the
      myricetin/HP-beta-CD inclusion complex. Consequently, the oral bioavailability of
      the myricetin/HP-beta-CD inclusion complex in rats was effectively increased 9.4
      fold over free myricetin, and its antioxidant activity was also improved. The
      present study provides useful information for the potential application of
      complexation with myricetin, a naturally occurring hydrophobic phenolic compound
      in herbal medicine.

PMID- 24906764
TI  - Structure-property relationships and biocompatibility of carbohydrate crosslinked
      polyurethanes.
AB  - Biocompatible and biodegradable polyurethanes (PUs) based on castor oil and
      polypropylene glycols (PPGs) were prepared using various carbohydrate
      crosslinkers: monosaccharide (glucose), disaccharide (sucrose) and
      polysaccharides (starch and cellulose). The mechanical and thermal properties
      were investigated and interpreted on the basis of SEM study. The advantage of
      incorporating various carbohydrates is to have tunable mechanical properties and
      biodegradability due to variety in their structure. The glass transition
      temperature and sorption behavior were dominated by the type of polyol than by
      the type of crosslinker. All the PUs were observed to be biodegradable as well as
      non-cytotoxic as revealed by MTT assay in normal lung cell line L132. The study
      supports the suitability of carbohydrates as important components of
      biocompatible PUs for development of biomedical devices. 

PMID- 24906765
TI  - Rheological and structural characterization of agar/whey proteins insoluble
      complexes.
AB  - Complex coacervation between whey proteins and carboxylated or highly sulphated
      polysaccharides has been widely studied. The aim of this work was to characterise
      a slightly sulphated polysaccharide (agar) and whey protein insoluble complexes
      in terms of yield, composition and physicochemical properties as well as to study
      their rheological behaviour for better understanding their structure. Unlike
      other sulphated polysaccharides, complexation of agar and whey protein at pH 3 in
      the absence of a buffering agent resulted in a coacervate that was a gel at 20
      degrees C with rheological properties and structure similar to those of simple
      agar gels, reinforced by proteins electrostatically aggregated to the agar
      network. The behaviour towards heat treatment was similar to that of agar alone,
      with a high thermal hysteresis and almost full reversibility. In the presence of
      citrate buffer, the result was a "flocculated solid", with low water content (75
      81%), whose properties were governed by protein behaviour. 

PMID- 24906766
TI  - Degradable starch nanoparticle assisted ethanol precipitation of DNA.
AB  - Precipitation of DNA from a large volume of aqueous solution is an important step
      in many molecular biology and analytical chemistry experiments. Currently, this
      is mainly achieved by ethanol precipitation, where a long-term incubation
      (usually overnight) at low temperature of -20 to -80 degrees C with high salt
      concentration is required. This method also requires a large quantity of DNA to
      form a visible pellet and was tested mainly for double-stranded DNA. To improve
      DNA precipitation, co-precipitating polymers such as linear polyacrylamide has
      been used. In this work, we report that starch nanoparticles (SNPs) can achieve
      convenient DNA precipitation at room temperature with a low salt concentration
      and short incubation time. This method requires as low as 0.01-0.1% SNPs and can
      precipitate both single- and double-stranded DNA of various lengths. The effect
      of salt concentration, pH and the crosslinking density of SNPs has been
      systematically studied. Compared to other types of precipitating agents, SNPs are
      highly biocompatible and can be degraded by a common enzyme (amylase). This work
      suggests a novel application of a bio-based material that is prepared in mass
      production. 

PMID- 24906767
TI  - 1D and 2D NMR of nanocellulose in aqueous colloidal suspensions.
AB  - This is the first report on surface structural elucidation of individual
      nanocellulose as colloidal suspensions by 1D 1H, 2D heteronuclear single quantum
      coherence (HSQC) as well as 13C nuclear magnetic resonance (NMR). 1H NMR of rice
      straw CNCs (4.7 nm thick, 143 nm long, 0.04 sulfate per AG or 19.0% surface
      hydroxyl to sulfate conversion) resembled that of homogeneous cellulose solution.
      Conventional 2D HSQC NMR of CNC, CNF 1.5 (2-14 nm thick, several micrometers
      long, 0.10 COOH per AG) and CNF10 (2.0 nm thick, up to 1 MUm long, 0.28 COOH per
      AG) gave H1:H2 ratios of 1.08:1, 0.97:1 and 0.94:1, respectively, all close to
      the theoretical 1:1 value for cellulose. The H1:H6 ratios determined from 2D HSQC
      NMR for CNCs, CNF1.5 and CNF10 were 1:1.47, 1:0.88 and 1:0.14, respectively, and
      corresponded to 26%, 56% and 93% C6 primary hydroxyl conversion to sulfate and
      carboxyl groups, consistent with, but more sensitive than those by conductometric
      titration and X-ray diffraction. Both 1H and 2D HSQC NMR data confirm that
      solution-state NMR detects nanocellulose surface carbons and protons primarily,
      validating this technique for direct surface characterization of nanocellulose in
      aqueous colloidal suspensions, presenting a sensitive and meaningful NMR tool for
      direct characterizing individual nanocellulose surfaces in never-dried state.

PMID- 24906768
TI  - Adsorption of chromate and cupric ions onto chitosan-coated cotton gauze.
AB  - A chitosan-coated cotton gauze was prepared by UV-curing and tested as adsorbent
      to remove copper (II) and chromium (VI) ions from water solutions. The adsorbent
      characterization was carried out by Scanning Electron Microscopy (SEM), Energy
      Dispersive X-ray Spectroscopy (EDX) and Fourier Transform Infrared Spectroscopy
      in Attenuated Total Reflection (FTIR-ATR). Adsorption of copper and chromium ions
      onto the gauze was tested in batch process at different experimental conditions.
      The effects of pH, temperature, contact time and metal ion concentration were
      investigated. The optimum adsorption took place at pH 3 for Cr(VI) and pH 5 for
      Cu(II) ions respectively, while the temperature did not affect the adsorption
      process. Pseudo-first and pseudo-second order models were used to investigate the
      adsorption kinetics which was found very fast and better described by the pseudo
      second order model for both metal ions. The adsorption of Cr(VI) ions was
      satisfactory described by the Langmuir isotherm, while that of Cu(II) ions showed
      a better agreement with the Freundlich model. 

PMID- 24906769
TI  - Active naringin-chitosan films: impact of UV irradiation.
AB  - Bioactive citrus extract-chitosan films were prepared through solvent casting
      evaporation method. The impact of near UV irradiation was studied to reach a
      better understanding of the film behavior. The antimicrobial activity of films
      against Listeria innocua was maintained after UV irradiation. To study the
      interaction between chitosan and citrus extract components, naringin (main
      component) was selected as the model compound. UV treatment caused modifications
      of the flavanone regardless of the solvent used for its dissolution, depending on
      the concentration of naringin in the film: the greater the concentration the
      lower the modification. DSC results suggested cross-links due to UV irradiation
      and interactions between naringin and chitosan. This was confirmed by a decrease
      in the naringin release from the irradiated samples. Naringin- and citrus extract
      chitosan films showed an increased absorbance in the UV region compared to pure
      chitosan films, showing potentiality for decreasing the lipid oxidation induced
      by UV light in foodstuffs. 

PMID- 24906770
TI  - Synergistic effects of guanidine-grafted CMC on enhancing antimicrobial activity
      and dry strength of paper.
AB  - In order to improve the strength property and antimicrobial activity of paper
      simultaneously, we prepared a novel multifunctional agent based on carboxymethyl
      cellulose (CMC) by a simple two-stage method. The first stage was the oxidation
      of CMC to obtain the dialdehyde CMC (DCMC), and the second stage was the graft of
      guanidine hydrochloride (GH) onto DCMC to obtain DCMC-GH polymer. The strength
      property and antimicrobial activity of DCMC-GH-coated copy paper have been
      studied by the tensile test and inhibition zone method, respectively. The results
      showed that the dry strength index could increase about 20% after the paper was
      coated with DCMC-GH. The coating of DCMC-GH on paper also resulted in excellent
      antimicrobial activities against Escherichia coli and Staphylococcus aureus, and
      the inhibition zone became larger as the GH content grafted on DCMC increased.
      The novel DCMC-GH polymer would be a multifunctional coating agent for food
      packaging paper. 

PMID- 24906771
TI  - Synthesis, characterization and cyclic voltammetric study of copper(II) and
      nickel(II) polymer chelates.
AB  - Graft copolymers based on dextran (Dx) and 2-acrylamido-2-methyl-1-propane
      sulphonic acid (AMPS) were synthesized by free radical initiated solution
      polymerization technique using ceric ammonium nitrate as initiator. These graft
      copolymers were used to prepare Cu(II) and Ni(II) chelates by reactions with
      Cu(II) and Ni(II) metal ions respectively. Graft copolymer and metal chelates
      were characterized by elemental analysis, intrinsic viscosity, FT-IR, scanning
      electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric
      analysis (TGA) and powder X-ray diffraction (XRD). Elemental analysis, intrinsic
      viscosity and FT-IR studies revealed the incorporation of metal ions to form
      metal chelates. SEM studies showed the change in morphology due to metal
      incorporation. From AFM studies it was observed that there was increase in Root
      mean square (RMS) roughness values in case of metal complexes. Metal chelates
      were observed to be thermally more stable than graft copolymer from TGA. UV-vis
      spectroscopy study revealed increase in absorbance values and cyclic voltammetric
      (CV) studies showed more than tenfold increase in redox current due to formation
      of Cu(II) and Ni(II) metal chelates. The binding constants of each complex
      determined by using UV-visible spectroscopy revealed that Cu(II) has more binding
      ability than Ni(II). 

PMID- 24906772
TI  - Effect of irradiated sodium alginate and phosphorus on biomass and artemisinin
      production in Artemisia annua.
AB  - It is now being realized that irradiation products of natural bioactive agents
      can also be beneficially utilized to impart value addition in agriculture by
      converting these bioactive agents into more useful form. Polysaccharides, such as
      sodium alginate, have proven to be wonderful growth promoting substances in their
      depolymerized form for various plants. Artemisinin has been increasingly popular
      as an effective and safe alternative therapy against malaria; also proved
      effective against the highly adaptable malaria parasite, which has already become
      resistant to many other drugs. The drug artemisinin can be extracted from the
      leafy tissues of Artemisia annua. Therefore, experiments were conducted with an
      aim to evaluate artemisinin production and overall plant development though
      depolymerized sodium alginate application and nutrient supply. In the present
      study, sodium alginate, irradiated by Co-60 gamma rays together with various
      phosphorus doses, was used to study their effect on growth, physiological and
      biochemical processes and production of artemisinin in A. annua. Among various
      applied doses of phosphorus fertilizer, P40 (40 kg Pha(-1)) together with ISA80
      (80 mg L(-1)) significantly improved all the parameters studied. Increase in
      plant height as well as weight was noted at this treatment. Dry leaf yield,
      artemisinin concentration in leaves and artemisinin yield was also significantly
      enhanced by the treatment.

PMID- 24906773
TI  - Chain conformation and immunomodulatory activity of a hyperbranched
      polysaccharide from Cordyceps sinensis.
AB  - A polysaccharide, named as cordysinan, extracted from natural Cordyceps sinensis,
      was identified as a hyperbranched heteropolysaccharide from the results of FT-IR,
      GC-MS, and carbohydrate analysis by carbohydrate gel electrophoresis analysis, as
      well as the degree of branching of cordysinan was 43.3%. The solution properties
      of cordysinan were investigated by using size exclusion chromatography coupled
      with multi-angle laser light scattering and triple detector array, respectively.
      The molecular weights, the radius of gyration and the intrinsic viscosity of
      cordysinan were determined as 22.45+/-0.26 kDa and 22.37 kDa, 15.4+/-2.4 nm and
      1.41 mL/g, respectively. By applying the polymer solution theory, the exponent
      (nu and alpha) values of <S2>g1/2=kMwv and [eta]=kMwalpha were calculated as 0.28
      and 0.42, respectively, which firstly revealed that cordysinan existed as a
      globular shape in 0.9% NaCl aqueous solution. Moreover, the results showed that
      cordysinan could obviously stimulate macrophages functions.

PMID- 24906774
TI  - A novel approach for the preparation of nanocrystalline cellulose by using
      phosphotungstic acid.
AB  - In this work, a sustainable and green process to prepare nanocrystalline
      cellulose (NCC) from bleached hardwood pulp was demonstrated. Rod-like
      nanocrystalline cellulose with the size of 15-40 nm in width and hundreds of
      nanometers in length was obtained through H3PW12O40 (HPW)-catalyzed hydrolysis of
      bleached pulp fibers under the mild reaction conditions. Thermogravimetric
      analysis revealed that the resulting NCC exhibited much higher thermal stability
      than the partially sulfated NCC (prepared by sulfuric acid). In addition, the
      concentrated HPW could be easily recovered and recycled through the extraction
      with diethyl ether, and the recovered HPW could be reused for several rounds of
      cellulose hydrolysis without activity lost. These fundamental studies are of
      crucial importance for the development and application of NCC products/NCC-based
      biomaterials with good thermal stability.

PMID- 24906775
TI  - Characterization of new natural cellulosic fiber from Cissus quadrangularis root.
AB  - Fiber reinforced polymer composites are replacing many metallic structures due to
      its high specific strength and modulus. However commonly used man-made E-glass
      fibers are hazardous for health and carcinogenic by nature. Comprehensive
      characterization of Cissus quadrangularis root fiber such as anatomical study,
      chemical analysis, physical analysis, FTIR, XRD, SEM analysis and thermo
      gravimetric analysis are done. The results are very encouraging for its
      application in fiber industries, composite manufacturing, etc. Due to its light
      weight and the presence of high cellulose content (77.17%) with very little wax
      (0.14%) provide high specific strength and good bonding properties. The flaky
      honeycomb outer surface and low microfibril angle revealed through electron
      microscopy contributes for its high modulus. The thermo gravimetric analysis
      indicates better thermal stability of the fiber up to 230 degrees C, which is
      well within the polymerization process temperature. 

PMID- 24906776
TI  - Highly exfoliated eco-friendly thermoplastic starch (TPS)/poly (lactic
      acid)(PLA)/clay nanocomposites using unmodified nanoclay.
AB  - Highly exfoliated, biodegradable thermoplastic starch (TPS)/polylactic acid
      (PLA)/sodium montmorillonite (NaMMT) nanocomposites were prepared by an eco
      friendly approach, involving in-situ gelatinization of potato starch in presence
      of dispersed nanoclay followed by melt mixing with PLA. The morphological
      analysis revealed that the NaMMT was selectively dispersed into the TPS in a
      highly delaminated manner. An increase in mechanical as well as thermomechanical
      properties was evident in the presence of PLA and more influenced in the presence
      of clay. The water absorption was significantly decreased in the presence of PLA
      (~8%) itself and both PLA and clay (~8-12%) in the nanocomposites. The improved
      mechanical properties along with its biodegradability might lead to a new green
      material in the area of packaging. 

PMID- 24906777
TI  - Thermoresponsive magnetic nanoparticle--aminated guar gum hydrogel system for
      sustained release of doxorubicin hydrochloride.
AB  - Hydrogel based sustained drug delivery system has evolved as an immense treatment
      method for solid tumors over the past few decades with long term theranostic
      ability. Here, we synthesized an injectable hydrogel system comprising
      biocompatible aminated guar gum, Fe3O4-ZnS core-shell nanoparticles and
      doxorubicin hydrochloride. We show that amination of guar gum resulted in
      attraction of water molecules thereby forming the hydrogel without using toxic
      crosslinking agents. Hydrogel formation was observed at 37 degrees C and is
      stable up to 95 degrees C. The prepared hydrogel is also stable over a wide pH
      range. The in vitro studies show that the maximum de-gelation and drug release up
      to 90% can be achieved after 20 days of incubation. Studies reveal that the drug
      and the core-shell nanoparticles can be released slowly from the hydrogel to
      provide the healing and diagnosis of the solid tumor thereby avoiding several
      drug administrations and total excision of organs. 

PMID- 24906778
TI  - Effect and mechanisms of curdlan sulfate on inhibiting HBV infection and acting
      as an HB vaccine adjuvant.
AB  - In this study, the effect and mechanisms of curdlan sulfate (CS3) on hepatitis B
      virus (HBV) infection and promoting immune response of the mice immunized with
      recombinant hepatitis B surface protein (HBsAg) were investigated. The results
      showed that CS3 could inhibit HBV infection of HepG2 and HepaRG cells, especially
      the process of HBV particle binding to the cell surfaces. The surface plasmon
      response (SPR) technology indicated that CS3 could bind with recombinant HBsAg
      and the binding ability depended on the content of sulfate groups on the
      polysaccharide chains. Co-administration of CS3 to BALB/c mice immunized with
      HBsAg significantly enhanced the influx of macrophages and dendritic cells in
      spleen, increased antigen-specific CD4+ and CD8+ cell numbers, and promoted
      splenocyte proliferation. The titer of HBsAg-specific antibodies was also
      augmented by use of CS3 as a vaccine adjuvant. The higher expression of
      interferon (IFN)-gamma, lower expression of interleukin (IL)-4, and higher
      IgG2a/IgG1 ratio within the anti-HBsAg antibodies in mice immunized with HBsAg
      plus CS3 than those in mice receiving HBsAg alone indicated that CS3 induced a
      shift toward a Th1-biased immune response. These results presented that CS3 could
      be developed as an immunotherapy agent or vaccine adjuvant for HBV infection
      treatment or prevention.

PMID- 24906779
TI  - A novel green approach for the preparation of cellulose nanowhiskers from white
      coir.
AB  - The aim of this work was to optimize the extraction of cellulose nanowhiskers
      (CNW) from unripe coconut husk fibers (CHF). The CHF was delignified using
      organosolv process, followed by alkaline bleaching (5% (w/w) H2O2+4% (w/w) NaOH;
      50 degrees C, 90 min). The CHF was subsequently hydrolyzed with 30% (v/v)
      sulfuric acid (60 degrees C, 360 min). The process yielded a partially
      delignified acetosolv cellulose pulp and acetic black liquor, from which the
      lignin was recovered. The CNW from the acetosolv pulp exhibited an average length
      of 172+/-88 nm and a diameter of 8+/-3 nm, (aspect ratio of 22+/-8). The surface
      charge of the CNW was -33 mV, indicating a stable aqueous colloidal suspension.
      The nanocrystals presented physical characteristics close to those extracted from
      cellulose pulp made by CHF chlorine-pulping. This approach offers the additional
      advantage of extracting the lignin as an alternative to eradication.

PMID- 24906780
TI  - Carboxymethylated-, hydroxypropylsulfonated- and quaternized xylan derivative
      films.
AB  - Under alkaline/water conditions carboxymethyl, 2-hydroxypropylsulfonate and
      trimethylammonium-2-hydroxypropyl groups were introduced into xylan in one step
      with the goal to prepare film specimens. The materials were characterized by NMR,
      SEC-MALS, TG/DTG/DTA, AFM and mechanical testing. The properties of triple,
      double and mono-substituted materials were compared. The numerical molar masses
      of the specimens were from 12.3 to 17.6 kg/mol with Mw/Mn from 1.27 to 1.34. The
      elastic modulus values are decreasing in order: xylan (X; 7354 MPa)>carboxymethyl
      xylan (CX; 6090MPa)>2-hydroxypropylsulfonate xylan (SX; 6000 MPa)>carboxymethyl/2
      hydroxypropylsulfonate xylan (CSX; 4490 MPa)>quaternized xylan (QX; 3600
      MPa)>carboxymethyl/quaternary/2-hydroxypropylsulfonate xylan (CQSX; 3380
      MPa)>carboxymethyl/quaternary xylan (CQX; 2805 MPa). The onset temperatures of SX
      (214 degrees C), CQSX (212 degrees C), QSX (211 degrees C) and CQX (207 degrees
      C) were higher than for X (205 degrees C). The roughness values of the film
      surfaces (3.634-18.667 nm) are higher on top than on the bottom of the specimen.

PMID- 24906781
TI  - Cyclodextrin-benzoic acid binding in salt solutions: effects of biologically
      relevant anions.
AB  - Inclusion complex formation of benzoic acid with alpha-, beta- and gamma
      cyclodextrins in water and in 0.2 M solutions of inorganic salts (KCl, KBr,
      KH2PO4 and K2SO4) has been studied by means of 1H NMR at 298.15 K. Binding
      constants have been determined and role of biologically active inorganic anions
      in the inclusion complex formation has been revealed. It has been shown that
      effects of the anions are determined not only by changing the ionic strength.
      More pronounced influence of Br- and H2PO4- compared with Cl- and SO4(2-) is
      caused by specific ion-molecular interactions, occurrence of which depends on the
      physical-chemical properties of the anions as well as on the binding mode of
      cyclodextrins with benzoic acid. Competing interactions of cyclodextrin-anion
      were observed in the presence of KBr, while the ternary complex formation was
      detected upon addition of KH2PO4.

PMID- 24906782
TI  - Characterization of bionanocomposite films prepared with agar and paper-mulberry
      pulp nanocellulose.
AB  - Crystallized nanocellulose (CNC) was separated from paper-mulberry (Broussonetia
      kazinoki Siebold) bast pulp by sulfuric acid hydrolysis method and they were
      blended with agar to prepare bionanocomposite films. The effect of CNC content
      (1, 3, 5 and 10 wt% based on agar) on the mechanical, water vapor permeability
      (WVP), and thermal properties of the nanocomposites were studied. Changes of the
      cellulose fibers in structure, morphology, crystallinity, and thermal properties
      of the films were evaluated using FT-IR, TEM, SEM, XRD, and TGA analysis methods.
      The CNC was composed of fibrous and spherical or elliptic granules of nano
      cellulose with sizes of 50-60 nm. Properties of agar film such as mechanical and
      water vapor barrier properties were improved significantly (p<0.05) by blending
      with the CNC. The tensile modulus and tensile strength of agar film increased by
      40% and 25%, respectively, in the composite film with 5 wt% of CNC, and the WVP
      of agar film decreased by 25% after formation of nanocomposite with 3 wt% of CNC.
      The CNC obtained from the paper-mulberry bast pulp can be used as a reinforcing
      agent for the preparation of bio-nanocomposites, and they have a high potential
      for the development of completely biodegradable food packaging materials.

PMID- 24906783
TI  - Synthesis of nano Cu2O on cotton: morphological, physical, biological and optical
      sensing characterizations.
AB  - In this paper, Cu2O nanoparticles were in situ synthesized on cotton fabric
      through a new simple and cost-effective chemical reduction method using copper
      sulfate, sodium hydroxide and ammonia. Cotton fabric participates as a reducing
      agent in reduction of copper sulfate and facilitates synthesis of cuprous oxide
      in nano-scale as a stabilizer. The produced cotton/nano Cu2O composite were
      characterized by X-ray diffraction, scanning electron microscopy and Energy
      dispersive X-ray spectroscopy. Interaction of Cu2O with cotton fabric in addition
      to alteration of cotton functional groups were studied by Fourier transforms
      infrared spectroscopy. The intermediate solution, copper-amine complex, was
      analyzed by ultraviolet-visible spectroscopy. The mechanical properties of the
      cotton/nano Cu2O composite were studied using Instron indicated a higher tensile
      strain. The antibacterial activity of the fabric samples showed considerable
      behavior against S. aureus and E. coli. Further, the treated fabric became highly
      hydrophobic and sensed ammonia and hydrogen peroxide chromatically. 

PMID- 24906784
TI  - One-step preparation of 2,3,6-tricarboxy cellulose.
AB  - Water-soluble sodium 2,3,6-tricarboxylate cellulose (NaTCC) or sodium
      mesotartarate/monohydrated glyoxilate alternating co-polyacetal was prepared from
      regenerated cellulose in a yield of 82% by one-step oxidation with catalytic
      amounts of 2-azaadamantane N-oxyl (AZADO), NaBr, and excess NaOCl in water at
      room temperature under alkaline conditions. The AZADO-oxidized product was shown
      to have an almost homogeneous NaTCC chemical structure by its 1H and 13C NMR
      spectra. The weight- and number-average molecular masses of the obtained NaTCC
      were 10,700 and 7000. When AZADO-mediated oxidation was applied to softwood
      bleached kraft pulp, a water-soluble oxidized product was obtained. However, it
      had a more heterogeneous chemical structure showing that the complete oxidation
      of the C2, C3, and C6 hydroxyls to carboxyls is difficult to achieve in native
      cellulose.

PMID- 24906785
TI  - Synthesis of a novel acrylated abietic acid-g-bacterial cellulose hydrogel by
      gamma irradiation.
AB  - Acrylated abietic acid (acrylated AbA) and acrylated abietic acid-grafted
      bacterial cellulose pH sensitive hydrogel (acrylated AbA-g-BC) were prepared by a
      one-pot synthesis. The successful dimerization of acrylic acid (AA) and abietic
      acid (AbA) and grafting of the dimer onto bacterial cellulose (BC) was confirmed
      by 13C solid state NMR as well as FT-IR. X-ray diffraction analysis showed
      characteristic peaks for AbA and BC; further, there was no effect of increasing
      amorphous AA content on the overall crystallinity of the hydrogel. Differential
      scanning calorimetry revealed a glass transition temperature of 80 degrees C. Gel
      fraction and swelling studies gave insight into the features of the hydrogel,
      suggesting that it was suitable for future applications such as drug delivery.
      Scanning electron microscopy observations showed an interesting interpenetrating
      network within the walls of hydrogel samples with the lowest levels of AA and
      gamma radiation doses. Cell viability test revealed that the synthesized hydrogel
      is safe for future use in biomedical applications.

PMID- 24906786
TI  - Cyclodextrin-coated denim fabrics as novel carriers for ingredient deliveries to
      the skin.
AB  - Garments with coverage of a large part of the body generate an exceptional
      opportunity for transferring active ingredient to the skin. A fabric finished
      with beta-cyclodextrin derivatives can play a role as a host for a next active
      substance as a guest. In this paper, different methods for permanent fixation of
      Monochlorotriazinyl-beta-Cyclodextrin (MCT)-beta-CD, on inner side of a denim
      fabric were investigated as a carrier with the purpose of substance formation
      inclusion complex with (MCT)-CD hydrophobic cavity. In order to fix MCT-CD on the
      fabric surface, two methods were investigated: (1) simultaneously or one step-
      and (2) pre- or two step-carbonating with sodium carbonate. Varying chemical and
      physical analyses such as gravimetrical and elemental analysis, FTIR
      spectroscopy, SEM images and fastness properties measurements, were studied to
      evaluate the quality of the host molecule stabilization on the textiles
      substrates and distinction of better application method. 

PMID- 24906787
TI  - Lead removal onto cross-linked low molecular weight chitosan pyruvic acid
      derivatives.
AB  - Adsorption capacity of cross-linked low molecular weight chitosan pyruvic acid
      derivatives CSnPA-GLA (n=8, 11) were examined by employing 2(3) factorial design
      method. Three (3) factors and two (2) levels of adsorbent dose (A) (0.05 and 0.1
      g), adsorbent type (B) (CS8PA-GLA and CS11PA-GLA) and concentration of lead
      solution (C) (1 and 3 mg/L) were considered. From the statistical analysis, all
      the main parameters (A, B and C) and some interactions of the main parameters (AC
      and ABC) had influence on the adsorption process at 5% significance level. The
      adsorption process was greatly influenced by the adsorbent type (B). The
      adsorption equilibrium results correlated well with the Freundlich isotherm
      model. The adsorption kinetic data also correlated well with the pseudo second
      order. The thermodynamic studies also revealed that the nature of lead adsorption
      was spontaneous and endothermic. The findings suggest that CS8PA-GLA is better
      than CS11PA-GLA for lead sorption.

PMID- 24906788
TI  - [Association between limited joint mobility syndrome and risk of accidental falls
      in diabetic patients].
AB  - INTRODUCTION: Limited joint mobility syndrome (LJMS) appears exclusively in both
      type 1 and type 2 diabetic patients. It is characterized by a limited range of
      digital motion, with involvement of small joints of the hands. It initially
      affects the proximal interphalangeal joints, followed by wrists, elbows,
      shoulders, knees, and axial skeleton. The diagnosis can be made by the simple
      "prayer sign" test. The objective was to study the prevalence of diabetic
      patients with LJMS, and to evaluate the association between LJMS and metabolic
      control, and the risk of accidental falls. PATIENTS AND METHODS: A cross
      sectional study was conducted in the San Fernando II Health Centre, Madrid
      (suburbs). The sample consisted of 184 patients with a diagnosis of diabetes of
      over 5 years from November to March, 2013. The prayer sign was used to define
      which patients had LJMS. Fall risk was determined using the Timed Up & Go test.
      RESULTS: A total of 99 patients (53.8%) (95% CI 46.6 to 61) had a positive prayer
      sign. No statistically significant relationship was found with HbA1c, but there
      was an association with the Timed Up & Go test (P<.001) (95% CI 1.173 to 1.611).
      The patients with LJMS had a moderate risk of falls compared with those without
      LJMS, which was of low risk. CONCLUSIONS: The prevalence of LJMS is high. This is
      the first study that shows a relationship between LJMS and the risk of falls in
      diabetic patients.

PMID- 24906789
TI  - Therapygenetics: 5-HTTLPR genotype predicts the response to exposure therapy for
      agoraphobia.
AB  - This study was intended to assess the extent to which the low-expression allele
      of the serotonin transporter gene promoter predicts better response to exposure
      based behavior therapy in patients with panic disorder with agoraphobia (PDA).
      Ninety-nine patients with PDA underwent a 1-week in vivo exposure-based behavior
      therapy program and provided saliva samples to extract genomic DNA and classify
      individuals according to four allelic forms (SA, SG, LA, LG) of the 5-HTT-linked
      polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype
      predicted change in avoidance behavior in PDA following treatment. After
      controlling for pre-treatment avoidance behavior, the 5-HTTLPR low-expression
      genotypes showed a more favorable response to exposure therapy two weeks
      following treatment, compared to the other patients. This study suggests a
      genetic contribution to treatment outcome following behavior therapy and
      implicates the serotonergic system in response to exposure-based treatments in
      PDA. 

PMID- 24906791
TI  - Attitudes of students and employees towards the implementation of a totally smoke
      free university campus policy at King Saud University in Saudi Arabia: a cross
      sectional baseline study on smoking behavior following the implementation of
      policy.
AB  - Tobacco smoking is the preventable health issue worldwide. The harmful
      consequences of tobacco smoking and exposure to second-hand tobacco smoke are
      well documented. The aim of this study is to compares the prevalence of smoking
      among students, faculty and staff and examines their interest to quit. Study also
      determines the difference on perceptions of smoking and non-smoking students,
      faculty and staff with regard to implementation of a smoke-free policy. A cross
      sectional survey was administered to one of the largest universities in Riyadh,
      Saudi Arabia during the academic year of 2013. A Likert scale was used on
      questionnaires towards attitude to smoking and smoking free policy. The Chi
      squared test was used to determine the difference of support on completely smoke
      free campus for smokers and non-smokers. Smoking rates were highest among staff
      members (36.8 %) followed by students (11.2 %) and faculty (6.4 %). About half of
      the smokers (53.7 %) within the university attempted to quit smoking. Students
      (OR 3.10, 95 % CI 1.00-9.60) and faculty (OR 4.06, 95 % CI 1.16-14.18) were more
      likely to make quit smoking than staff members. Majority of the respondents (89.6
      %) were supportive of a smoking--free policy and indicated that should be
      strictly enforced especially into public places. Results also showed that smokers
      were more likely to support a smoke-free policy if there are no fines or
      penalties. These baseline findings will provide information among administrators
      in formulating and carrying out a total smoke free policy. Although the majority
      of people within the King Saud University demonstrate a high support for a smoke
      free policy, administrators should consider difference between smokers and non
      smokers attitudes when implementing such a policy.

PMID- 24906790
TI  - Functional remediation for patients with bipolar II disorder: improvement of
      functioning and subsyndromal symptoms.
AB  - Recently, Functional Remediation (FR) has proven to be effective in improving the
      functional outcome of euthymic bipolar patients. The aim of this study was to
      test the efficacy of the FR program in a subsample of euthymic bipolar II
      patients (BPII). A post-hoc analyses were undertaken using data of 53 BPII
      outpatients who had participated in a multicenter, rater-blind, randomized,
      controlled trial exploring the efficacy of FR (n=17) as compared with a
      Psychoeducation group (PSY) (n=19) and a treatment as usual control group (TAU
      n=17). The primary outcome variable was the functional improvement defined as the
      mean change in the Functioning Assessment Short Test (FAST) from baseline to
      endpoint after the intervention. Regarding the treatment effect, data reveal a
      significant functional improvement from baseline to endpoint, suggestive for an
      interaction between program pertinence and time (pre-post). Nevertheless, Tukey's
      post-hoc test only revealed a trend in favor of a better outcome for FR when
      compared to the other two groups. We also found an interaction between program
      pertinence and time when analysing the subdepressive symptoms, with BPII patients
      in FR showing a significant reduction when compared to the PSY group. Our results
      suggest that the FR appears to be effective in improving the overall functional
      outcome in BPII, as well as in reducing subdepressive symptoms. 

PMID- 24906792
TI  - Is prediffusion test an alternative to improve accuracy in screening hVISA
      strains and to detect susceptibility to glycopeptides/lipopeptides?
AB  - The characterization of heteroresistant vancomycin-intermediate Staphylococcus
      aureus strains (hVISA) is even more challenging, as no routine standardized
      laboratory methods are available. A total of 124 S. aureus isolates recovered
      from inpatients attended in hospitals of Santa Catarina State, Southern Brazil,
      were evaluated. The MIC of vancomycin, teicoplanin, and daptomycin was determined
      by Etest and prediffusion tests using NeoSensitabs(r) tablets. All isolates were
      susceptible to vancomycin (MICs: 0.5-3 MUg/mL) by Etest. However, according to
      prediffusion test, 17 isolates presented reduced susceptibility to vancomycin,
      and of these, 12 were confirmed as hVISA using populational analysis. Considering
      daptomycin, prediffusion results were in agreement with susceptibility data
      (MICs), as all isolates were susceptible. Considering that characterizing hVISA
      is challenging and that MIC determination is not adequate to characterize this
      phenotype, prediffusion test was a viable alternative to screening hVISA and
      reduced susceptibility to vancomycin. It was simple and low cost, with accuracy
      comparable to other well-established methods. 

PMID- 24906793
TI  - Elevated pre-transplant pulmonary vascular resistance is not associated with
      mortality in children without congenital heart disease: a multicenter study.
AB  - BACKGROUND: Traditionally, an elevated pulmonary vascular resistance index (PVRI)
      has been a relative contraindication to pediatric orthotopic heart
      transplantation. This study examined the risk of elevated pre-transplant PVRI on
      early (30-day) and intermediate-term mortality in pediatric heart transplant
      recipients without congenital heart disease (CHD). METHODS: A review of the
      prospective multicenter Pediatric Heart Transplant Study registry identified all
      patients without CHD in whom a pre-transplant PVRI was recorded. Of 35
      participating centers, 29 reported heart transplants in children with a markedly
      elevated PVRI (> 5 WU * m(2), corresponding to the highest quartile). Multiphase
      parametric analysis was performed, adjusting for potential risk factors to assess
      the association of PVRI with early and intermediate-term mortality. RESULTS:
      Between 1993 and 2011, 1,909 children without CHD underwent heart transplantation
      at a median age of 9.7 years (range, 1.6 months-18 years). Of those, 795 (42%)
      had a recorded or calculable pre-transplant PVRI, and PVRI > 5 WU * m(2) was
      present in 193 patients (24%). For all recipients, median pre-transplant PVRI was
      3.15 WU * m(2) (range, 0.4-23 WU * m(2)); 2.8 WU * m(2) in infants < 1 year, 3.5
      WU * m(2) in patients aged 1 to 10 years, and 3.0 WU * m(2) in patients aged > 10
      years (p = 0.03). Multivariable hazard analysis controlling for graft ischemic
      time and pre-transplant ventilation showed no association of elevated PVRI with
      early mortality (relative risk, 1.2; p = 0.66), nor with intermediate mortality
      when controlled for year of transplant, age, race, and pre-sensitization
      (relative risk, 0.7; p = 0.27). CONCLUSIONS: Elevation of PVRI did not affect
      post-transplant survival in this large, multicenter cohort of pediatric heart
      transplant recipients without CHD, suggesting that the barrier of elevated PVRI
      can be successfully overcome in this population.

PMID- 24906795
TI  - Early Pliocene Cercopithecidae from Woranso-Mille (Central Afar, Ethiopia) and
      the origins of the Theropithecus oswaldi lineage.
AB  - A large series of fossil cercopithecids has been recovered from the hominid
      bearing Woranso-Mille site, Afar State, northeastern Ethiopia. Here we report the
      taxonomy of those specimens from the Am-Ado, Aralee Issie, Korsi Dora, Makah
      Mera, and Mesgid Dora collection areas, which are all roughly contemporaneous and
      dated to between 3.6 and 3.8 million years ago. This series includes a minimum of
      two cercopithecine and three colobine species. Theropithecus oswaldi cf. darti is
      by far the most common species in the assemblage, making up over 90% of
      identifiable cercopithecid specimens. There is also at least one other species of
      papionin, which cannot be currently assigned to a genus. The colobines are here
      allocated to Cercopithecoides cf. meaveae and two other species, one small and
      one large, that cannot be currently assigned to genus. The T. oswaldi cf. darti
      series from Woranso-Mille is both the earliest and largest identified to date. It
      documents the earliest occurrence of the T. oswaldi lineage and strongly suggests
      that parallel evolution of molar morphology has occurred within the genus between
      T. oswaldi and Theropithecus brumpti. Given the dominance of monkeys at Woranso
      Mille, and the preponderance of Theropithecus among cercopithecids, T. o. cf.
      darti is likely to be the most common mammal present at the 3.6-3.8 million-years
      old localities of the Woranso-Mille study area. Some explanations for this
      unusual occurrence are explored, and implications for the paleoenvironment at
      Woranso-Mille are also discussed.

PMID- 24906796
TI  - Detection and molecular characterisation of Giardia lamblia genotypes in Sharjah,
      United Arab Emirates.
AB  - BACKGROUND: No data are available on Giardia lamblia genotypes in the United Arab
      Emirates (UAE). This study aimed to identify G. lamblia from DNA extracted from
      human stool samples to gain information on its prevalence and to perform
      molecular analysis on isolates collected from expatriates from different
      localities residing in Sharjah, UAE. METHODS: In total, 111 healthy expatriates
      residing in Sharjah were screened for G. lamblia using nested PCR amplification
      of the small subunit ribosomal RNA (ssu-rRNA) gene. Positive samples were
      genotyped using a nested PCR amplifying the triosephosphate isomerase (tpi) gene
      to differentiate between the two human assemblages (A and B). A subset of the PCR
      products (n=23) were sequenced and their phylogenetic relationships were
      determined. RESULTS: Of the 111 participants, 67 (60.4%) were identified as
      positive for the ssu-rRNA gene. When genotyped for the tpi gene, 18.9% (21/111)
      were of assemblage A, 17.1% (19/111) belonged to assemblage B and 5.4% (6/111)
      showed patterns compatible with mixed infections. A strong correlation between
      the presence of diarrhoea and assemblage B was observed (chi(2)=10.553; p=0.001).
      Moreover, an association was also observed between mixed infections (A+B) and
      diarrhoea (chi(2)=8.899; p=0.003). No correlation between age, gender and
      geographic origin of the infected individual was noted. Phylogenetic analysis
      showed three clusters for the tpi gene. No relationship between the clusters and
      the origin of samples was noted. CONCLUSION: This study is the first to determine
      the infection rate and genotypic composition of Giardia in Sharjah, UAE.

PMID- 24906794
TI  - Efficacy of extracorporeal photopheresis in clearance of antibodies to donor
      specific and lung-specific antigens in lung transplant recipients.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) has been used to treat chronic
      rejection after lung transplantation (LTx). We investigated the effect of ECP on
      several immune parameters that have been associated with poor lung function,
      including donor-specific antibodies (DSA) to human leukocyte antigen (HLA),
      antibodies against the lung-associated self-antigens (SAg), Kalpha1-tubulin
      (Kalpha1T), collagen I and V, and circulating levels of pro-inflammatory and anti
      inflammatory cytokines. METHODS: Sera were collected from post-LTx patients
      diagnosed with bronchiolitis obliterans before and 6 months after initiation of
      ECP. DSA and cytokine levels were measured by Luminex (Invitrogen, Carlsbad, CA).
      Changes in lung function over the 6 months preceding and after the initiation of
      ECP were measured by retrospective analysis of spirometry performed at routine
      clinic visits. RESULTS: ECP was associated with a significant decline in DSA
      levels as well as antibodies to lung-associated SAg. ECP also reduced circulating
      levels of pro-inflammatory cytokines and increased levels of anti-inflammatory
      cytokines. These immunologic changes were associated with a significant 63%
      reduction in the rate of decline in forced expiratory volume in 1 second over a 1
      year period. Though statistically insignificant, a higher rate of clearance of
      antibodies to lung-associated SAg was strongly associated with better response to
      ECP. CONCLUSIONS: ECP is associated with a reduction in the levels of circulating
      DSA, antibodies to lung-associated SAg (Kalpha1T, collagen I, and collagen V),
      and circulating levels of several pro-inflammatory cytokines. We propose that
      these changes contribute to the beneficial effect of ECP in reducing the decline
      in lung function.

PMID- 24906797
TI  - Sorting of GPI-anchored proteins from yeast to mammals--common pathways at
      different sites?
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are luminal
      secretory cargos that are attached by a post-translational glycolipid
      modification, the GPI anchor, to the external leaflet of the plasma membrane. GPI
      APs are conserved among eukaryotes and possess many diverse and vital functions
      for which the GPI membrane attachment appears to be essential. The presence of
      the GPI anchor and its subsequent modifications along the secretory pathway
      confer to the anchored proteins unique trafficking properties that make GPI-APs
      an exceptional system to study mechanisms of sorting. In this Commentary, we
      discuss the recent advances in the field of GPI-AP sorting focusing on the
      mechanisms operating at the level of the exit from the ER and from the trans
      Golgi network (TGN), which take place, respectively, in yeast and in polarized
      mammalian cells. By considering the similarities and differences between these
      two sorting events, we present unifying principles that appear to work at
      different sorting stations and in different organisms. 

PMID- 24906798
TI  - The histone variant composition of centromeres is controlled by the pericentric
      heterochromatin state during the cell cycle.
AB  - Correct chromosome segregation requires a unique chromatin environment at
      centromeres and in their vicinity. Here, we address how the deposition of
      canonical H2A and H2A.Z histone variants is controlled at pericentric
      heterochromatin (PHC). Whereas in euchromatin newly synthesized H2A and H2A.Z are
      deposited throughout the cell cycle, we reveal two discrete waves of deposition
      at PHC - during mid to late S phase in a replication-dependent manner for H2A and
      during G1 phase for H2A.Z. This G1 cell cycle restriction is lost when
      heterochromatin features are altered, leading to the accumulation of H2A.Z at the
      domain. Interestingly, compromising PHC integrity also impacts upon neighboring
      centric chromatin, increasing the amount of centromeric CENP-A without changing
      the timing of its deposition. We conclude that the higher-order chromatin
      structure at the pericentric domain influences dynamics at the nucleosomal level
      within centromeric chromatin. The two different modes of rearrangement of the PHC
      during the cell cycle provide distinct opportunities to replenish one or the
      other H2A variant, highlighting PHC integrity as a potential signal to regulate
      the deposition timing and stoichiometry of histone variants at the centromere. 

PMID- 24906799
TI  - The ubiquitin-conjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for
      Parkin-dependent mitophagy.
AB  - Depolarized mitochondria are degraded by mitophagy in a process that depends on
      the Parkinson's disease gene products PINK1 and Parkin. This is accompanied by
      ubiquitylation of several mitochondrial substrates. The roles of E2 ubiquitin
      conjugating enzymes (UBE2) in mitophagy are poorly understood. Here, we
      investigate a set of UBE2 enzymes that might regulate Parkin-mediated mitophagy.
      Knockdown of the E2 enzymes UBE2N, UBE2L3 or UBE2D2 and UBE2D3 (UBE2D2/3)
      significantly reduced autophagic clearance of depolarized mitochondria. However,
      this did not interfere with mitochondrial PINK1 stabilization and Parkin
      translocation. UBE2N knockdown prevented specifically K63-linked ubiquitylation
      at mitochondrial sites. Nevertheless, polyubiquitin and p62 (officially known as
      SQSTM1) were still found on mitochondria after individual UBE2 knockdown.
      Knockdown of all of these UBE2s together significantly reduced mitochondrial
      polyubiquitylation and p62 recruitment. Moreover, reduced ubiquitylation of
      mitofusins, the mitochondrial import receptor subunits TOM20 and TOM70, the
      voltage-dependent anion channel protein 1 and Parkin was observed in cells
      silenced for all of these UBE2s. A version of Parkin with a mutation in the
      active site (C431S) failed to ubiquitylate these mitochondrial substrates even in
      the presence of UBE2s. We conclude that UBE2N, UBE2L3 and UBE2D2/3
      synergistically contribute to Parkin-mediated mitophagy. 

PMID- 24906800
TI  - Yeast phospholipid biosynthesis is linked to mRNA localization.
AB  - Regulation of the localization of mRNAs and local translation are universal
      features in eukaryotes and contribute to cellular asymmetry and differentiation.
      In Saccharomyces cerevisiae, localization of mRNAs that encode membrane proteins
      requires the She protein machinery, including the RNA-binding protein She2p, as
      well as movement of the cortical endoplasmic reticulum (cER) to the yeast bud. In
      a screen for ER-specific proteins necessary for the directional transport of WSC2
      and EAR1 mRNAs, we have identified enzymes that are involved in phospholipid
      metabolism. Loss of the phospholipid methyltransferase Cho2p, which showed the
      strongest impact on mRNA localization, disturbs mRNA localization, as well as ER
      morphology and segregation, owing to an increase in the amount of cellular
      phosphatidylethanolamine (PtdEtn). Mislocalized mRNPs containing She2p colocalize
      with aggregated cER structures, suggestive of the entrapment of mRNA and She2p by
      the elevated PtdEtn level. This was confirmed by the elevated binding of She2p to
      PtdEtn-containing liposomes. These findings underscore the importance of ER
      membrane integrity in mRNA transport. 

PMID- 24906801
TI  - Left ventricular functional recovery and remodeling in low-flow low-gradient
      severe aortic stenosis after transcatheter aortic valve implantation.
AB  - BACKGROUND: Speckle-tracking-derived global longitudinal strain (GLS) is a more
      sensitive method of detecting left ventricular (LV) functional recovery after
      transcatheter aortic valve implantation (TAVI) in patients with severe aortic
      stenosis. However, it remains unknown whether LV function improves in patients
      with low-flow, low-gradient severe aortic stenosis (LFLGSAS) after TAVI. The aim
      of the present was to evaluate LV functional recovery and remodeling after TAVI
      in patients with LFLGSAS. METHODS: Sixty-eight patients (57% men; mean age, 79.1
      +/- 7.1 years) with LFLGSAS treated with TAVI were evaluated. LV function and
      remodeling were investigated before TAVI and at 6 and 12 months after TAVI. All
      echocardiographic data were prospectively collected, and GLS was retrospectively
      analyzed. RESULTS: Among patients with LFLGSAS, 35 (52%) had low LV ejection
      fraction (LVEF) (<50%), and 33 (48%) had preserved LVEF (>=50%). The low-LVEF
      group had significantly more impaired GLS than the group with preserved LVEF (
      8.3 +/- 2.6% vs -13.3 +/- 3.5%, P < .001). LV systolic function improved after
      TAVI in both groups. Although in the group of patients with low LVEF, all
      functional parameters improved, in the group of patients with preserved LVEF,
      only strain-derived parameters significantly improved. There were significant
      decreases in absolute LV wall thickness and relative wall thickness and a trend
      toward decreased LV mass index in both LVEF groups. LV volumes decreased
      significantly in those with low LVEF but not in those with preserved LVEF.
      Baseline GLS but not LVEF group was independently associated to GLS improvement
      at 12 months after TAVI. CONCLUSIONS: Patients with LFLGSAS with low and
      preserved LVEF had a significant improvement in LV function after TAVI, as
      assessed by GLS. Absolute and relative LV wall thickness decreased in both groups
      of patients, but only those with low LVEF had reductions in LV volumes.

PMID- 24906802
TI  - Untreated aortic valve stenosis identified at the time of coronary artery bypass
      grafting: thresholds associated with adverse prognosis.
AB  - OBJECTIVES: Aortic valve replacement (AVR) for severe aortic valve stenosis (AS)
      is a Class I indication at the time of coronary artery bypass grafting (CABG).
      Management of less-than-severe AS in patients undergoing CABG is uncertain
      however, because the thresholds at which untreated AS impacts long-term outcome
      are unclear. METHODS: We identified 312 patients who underwent isolated CABG
      between 1993 and 2006 with mild or moderate AS [aortic valve area (AVA) 1-2
      cm(2)], and matched them to patients undergoing CABG alone during the same period
      with similar characteristics but without AS (AVA >2 cm(2)). Long-term survival
      after CABG and its determinants were analysed using Cox proportional hazards
      models with AVR as a time-dependent covariate. RESULTS: Late survival was lower
      in patients with untreated moderate AS (12 years 23 +/- 5.1%) versus mild (42 +/-
      3.8%) or no AS (38 +/- 3.3%) (P = 0.01). Adjusting for age, ejection fraction,
      heart failure, creatinine, diabetes, peripheral vascular disease (PVD) and
      interval AVR, moderate AS independently predicted higher mortality [hazard rate
      (HR) 2.01, 95% confidence interval (CI) 1.49-2.73; P < 0.001]; whereas
      incremental risk was insignificant for patients with mild AS (HR 1.09, 95% CI
      0.85-1.66; P = 0.33). Further stratification showed that highest late
      postoperative mortality occurred with an AVA of 1-1.25 cm(2) (adjusted HR 2.45,
      95% CI 1.57-3.82; P < 0.001), while risk was intermediate with an AVA of 1.25-1.5
      cm(2) (HR 1.83, 95% CI 1.28-2.61; P = 0.001). CONCLUSIONS: Untreated moderate AS
      is an independent determinant of excess late mortality following isolated CABG,
      and mortality risk increases with decreasing AVA. Those with moderate-to-severe
      AS (AVA 1-1.25 cm(2)) have more than 2-fold greater long-term mortality compared
      with those without AS. These data define AS severity thresholds for clinical
      trials aimed at defining whether valve intervention might mitigate this risk.

PMID- 24906803
TI  - hsphase: an R package for pedigree reconstruction, detection of recombination
      events, phasing and imputation of half-sib family groups.
AB  - BACKGROUND: Identification of recombination events and which chromosomal segments
      contributed to an individual is useful for a number of applications in genomic
      analyses including haplotyping, imputation, signatures of selection, and improved
      estimates of relationship and probability of identity by descent. Genotypic data
      on half-sib family groups are widely available in livestock genomics. This
      structure makes it possible to identify recombination events accurately even with
      only a few individuals and it lends itself well to a range of applications such
      as parentage assignment and pedigree verification. RESULTS: Here we present
      hsphase, an R package that exploits the genetic structure found in half-sib
      livestock data to identify and count recombination events, impute and phase un
      genotyped sires and phase its offspring. The package also allows reconstruction
      of family groups (pedigree inference), identification of pedigree errors and
      parentage assignment. Additional functions in the package allow identification of
      genomic mapping errors, imputation of paternal high density genotypes from low
      density genotypes, evaluation of phasing results either from hsphase or from
      other phasing programs. Various diagnostic plotting functions permit rapid visual
      inspection of results and evaluation of datasets. CONCLUSION: The hsphase package
      provides a suite of functions for analysis and visualization of genomic
      structures in half-sib family groups implemented in the widely used R programming
      environment. Low level functions were implemented in C++ and parallelized to
      improve performance. hsphase was primarily designed for use with high density SNP
      array data but it is fast enough to run directly on sequence data once they
      become more widely available. The package is available (GPL 3) from the
      Comprehensive R Archive Network (CRAN) or from http://www
      personal.une.edu.au/~cgondro2/hsphase.htm.

PMID- 24906804
TI  - Mitochondria and metabolic control of the aging process.

PMID- 24906805
TI  - Quality of reporting of systematic reviews published in "evidence-based" Chinese
      journals.
AB  - BACKGROUND: The number of systematic reviews (SRs)/meta-analyses (MAs) has
      increased dramatically in China over the past decades. However, evaluation of
      quality of reporting of systematic reviews published has not been undertaken. The
      objective of this study is to evaluate the quality of reporting of SRs/MAs
      assessing efficacy and/or harms of clinical interventions published in "evidence
      based" Chinese journals. METHODS: Web-based database searches were conducted for
      the Chinese Journal of Evidence-based Medicine, the Journal of Evidence-Based
      Medicine, the Chinese Journal of Evidence Based Pediatrics, and the Chinese
      Journal of Evidence-Based Cardiovascular Medicine. SRs/MAs assessing efficacy
      and/or harms of clinical interventions were included. The cut-off was December
      31st 2011. The PRISMA statement was applied to assess the quality of reporting.
      Each item was assessed as follows: 'Yes' for total compliance, scored '1';
      'partial' for partial compliance, scored '0.5'; and 'No' for non-compliance,
      scored '0'. The review was considered to have major flaws if it received a total
      score of <=15.0, minor flaws if it received a total score of 15.5 to 21.0, and
      minimal flaws if it received a total score 21.5 to 27.0. Odds ratios were used
      for binary variables, and the mean difference was used for continuous variables.
      Analyses were performed using RevMan 5.0 software. RESULTS: Overall, 487 SRs/MAs
      were identified and assessed. The included reviews had medium quality with minor
      flaws based on PRISMA total scores (range: 8.5-26.0; mean: 19.6 +/- 3.3). The
      stratified analysis showed that SRs/MAs with more than 3 authors, from a
      university, hospital + university cooperation, multiple affiliations (>=2), and
      funding have significantly higher quality of reporting of SRs/MAs; 58% of the
      included reviews were considered to have minor flaws (total score of 15.6 to
      21.0). Only 9.6% of reviews were considered to have major flaws. Specific areas
      needing improvement in reporting include the abstract, protocol and registration,
      and characteristics of the search. CONCLUSIONS: The reporting of SRs published in
      "evidence-based" Chinese journals is poor and needs to be improved in order for
      reviews to be useful. SR authors should use the PRISMA checklist to ensure
      complete and accurate accounts of their SRs.

PMID- 24906806
TI  - Mitigating errors caused by interruptions during medication verification and
      administration: interventions in a simulated ambulatory chemotherapy setting.
AB  - BACKGROUND: Nurses are frequently interrupted during medication verification and
      administration; however, few interventions exist to mitigate resulting errors,
      and the impact of these interventions on medication safety is poorly understood.
      OBJECTIVE: The study objectives were to (A) assess the effects of interruptions
      on medication verification and administration errors, and (B) design and test the
      effectiveness of targeted interventions at reducing these errors. METHODS: The
      study focused on medication verification and administration in an ambulatory
      chemotherapy setting. A simulation laboratory experiment was conducted to
      determine interruption-related error rates during specific medication
      verification and administration tasks. Interventions to reduce these errors were
      developed through a participatory design process, and their error reduction
      effectiveness was assessed through a postintervention experiment. RESULTS:
      Significantly more nurses committed medication errors when interrupted than when
      uninterrupted. With use of interventions when interrupted, significantly fewer
      nurses made errors in verifying medication volumes contained in syringes (16/18;
      89% preintervention error rate vs 11/19; 58% postintervention error rate;
      p=0.038; Fisher's exact test) and programmed in ambulatory pumps (17/18; 94%
      preintervention vs 11/19; 58% postintervention; p=0.012). The rate of error
      commission significantly decreased with use of interventions when interrupted
      during intravenous push (16/18; 89% preintervention vs 6/19; 32%
      postintervention; p=0.017) and pump programming (7/18; 39% preintervention vs
      1/19; 5% postintervention; p=0.017). No statistically significant differences
      were observed for other medication verification tasks. CONCLUSIONS: Interruptions
      can lead to medication verification and administration errors. Interventions were
      highly effective at reducing unanticipated errors of commission in medication
      administration tasks, but showed mixed effectiveness at reducing predictable
      errors of detection in medication verification tasks. These findings can be
      generalised and adapted to mitigate interruption-related errors in other settings
      where medication verification and administration are required.

PMID- 24906807
TI  - Modelling and seizure prediction.

PMID- 24906808
TI  - Correlations between word intelligibility under reverberation and speech auditory
      brainstem responses in elderly listeners.
AB  - OBJECTIVE: To investigate the relationship between speech auditory brainstem
      responses (speech ABRs) and word intelligibility under reverberation in elderly
      adults. METHODS: Word intelligibility for words under four reverberation times
      (RTs) of 0, 0.5, 1.0, 1.5s, and speech ABRs to the speech syllable/da/ were
      obtained from 30 elderly listeners. Root mean square (RMS) amplitudes and
      discrete Fourier transform (DFT) amplitudes were calculated for ADD and SUB
      responses in the speech ABRs. RESULTS: No significant correlations were found
      between the word intelligibility scores under reverberation and the ADD response
      components. However, in the SUB responses we found that the DFT amplitudes
      associated with H4-SUB, H5-SUB, H8-SUB, H9-SUB and H10-SUB significantly
      correlated with the word intelligibility scores for words under reverberation.
      With Bonferroni correction, the DFT amplitudes for H5-SUB and the intelligibility
      scores for words with the RT of 0.5s and 1.5s were significant. CONCLUSIONS: Word
      intelligibility under reverberation in elderly listeners is related to their
      ability to encode the temporal fine structure of speech. SIGNIFICANCE: The
      results expand knowledge about subcortical responses of elderly listeners in
      daily-life listening situations. The SUB responses of speech ABR could be useful
      as an objective indicator to predict word intelligibility under reverberation.

PMID- 24906809
TI  - An evaluation of the EOS X-ray imaging system in pelvimetry.
AB  - OBJECTIVES: To demonstrate the reliability of the EOS imaging system in measuring
      the internal diameters of the bony pelvis. MATERIALS AND METHODS: A prospective
      study comparing the results of the pelvimetry of 18 dry pelvises carried out on
      the EOS imaging system to measurements taken manually and using the two current
      gold standard CT methods. Pelvimetric measurements of each pelvic bone were
      obtained using four methods and compared: direct manual measurements, spiral and
      sequential CT pelvimetry, and 2D-3D low-dose biplanar X-rays. The various
      obstetric diameters were measured to the millimetre and compared. RESULTS: There
      was no significant difference in the different diameters assessed, with the
      exception of the interspinous diameter. There was a highly significant
      correlation (P < 0.001) between the values measured manually and by EOS for the
      Magnin index (Pearson = 0.98), the obstetric conjugate diameter (Pearson = 0.99),
      and the median transverse diameter (Pearson = 0.87). CONCLUSION: The EOS imaging
      system allows for an ex vivo determination of the obstetrical diameters that is
      reliable enough to estimate obstetric prognosis, producing comparable
      measurements to CT. In view of concerns about protection from radiation, this low
      dose imaging technique could become, after in vivo prospective validation, the
      new gold standard for pelvimetry and therefore a good alternative to CT.

PMID- 24906810
TI  - Radiological evaluation of response to treatment: application to metastatic renal
      cancers receiving anti-angiogenic treatment.
AB  - Targeted therapies have considerably improved the prognosis of patients with
      metastatic renal cancer (mRCC) but there are no reliable response assessment
      criteria reflecting the clinical benefits, because there is no regression in
      size, or it is delayed. Such criteria would help early identification of non
      responders, who would then benefit from a change of treatment, and would avoid
      their being subjected to unnecessary side effects related to the treatment. We
      will review the imaging techniques currently available for evaluating tumour
      response in mRCC patients, including the response evaluation criteria in solid
      tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size
      and attenuation criteria (SACT). We will also discuss functional imaging
      techniques, which are based on the physiological characteristics of the tumours,
      such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI,
      DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET)
      tracers. It is not possible at present to propose a unanimously acknowledged
      criterion for evaluating tumour response to targeted therapy. However, there is a
      real need for this according to oncologists and the pharmaceutical industry, and
      radiologists need to be involved in reflecting on the subject. 

PMID- 24906811
TI  - CORR(r) ORS Richard A. Brand Award for Outstanding Orthopaedic Research:
      Engineering flexor tendon repair with lubricant, cells, and cytokines in a canine
      model.
AB  - BACKGROUND: Adhesions and poor healing are complications of flexor tendon repair.
      QUESTIONS/PURPOSES: The purpose of this study was to investigate a tissue
      engineering approach to improve functional outcomes after flexor tendon repair in
      a canine model. METHODS: Flexor digitorum profundus tendons were lacerated and
      repaired in 60 dogs that were followed for 10, 21, or 42 days. One randomly
      selected repair from either the second or fifth digit in one paw in each dog was
      treated with carbodiimide-derivatized hyaluronic acid, gelatin, and lubricin plus
      autologous bone marrow stromal cells stimulated with growth and differentiation
      factor 5; control repair tendons were not treated. Digits were analyzed by
      adhesion score, work of flexion, tendon-pulley friction, failure force, and
      histology. RESULTS: In the control group, 35 of 52 control tendons had adhesions,
      whereas 19 of 49 treated tendons had adhesions. The number of repaired tendons
      with adhesions in the control group was greater than the number in the treated
      group at all three times (p = 0.005). The normalized work of flexion in treated
      tendons was 0.28 (+/- 0.08), 0.29 (+/- 0.19), and 0.32 (+/- 0.22) N/mm/ degrees 
      at Day 10, Day 21, and Day 42 respectively, compared with the untreated tendons
      of 0.46 (+/- 0.19) at Day 10 (effect size, 1.5; p = 0.01), 0.77 (+/- 0.49) at Day
      21 (effect size, 1.4; p < 0.001), and 1.17 (+/- 0.82) N/mm/ degrees  at Day 42
      (effect size, 1.6; p < 0.001). The friction data were comparable to the work of
      flexion data at all times. The repaired tendon failure force in the untreated
      group at 42 days was 70.2 N (+/- 8.77), which was greater than the treated
      tendons 44.7 N (+/- 8.53) (effect size, 1.9; p < 0.001). Histologically, treated
      repairs had a smooth surface with intrinsic healing, whereas control repairs had
      surface adhesions and extrinsic healing. CONCLUSIONS: Our study provides evidence
      that tissue engineering coupled with restoration of tendon gliding can improve
      the quality of tendon healing in a large animal in vivo model. CLINICAL
      RELEVANCE: Tissue engineering may enhance intrinsic tendon healing and thus
      improve the functional outcomes of flexor tendon repair.

PMID- 24906812
TI  - Patient and procedure-specific risk factors for deep infection after primary
      shoulder arthroplasty.
AB  - BACKGROUND: Deep infection after shoulder arthroplasty is a diagnostic and
      therapeutic challenge. The current literature on this topic is from single
      institutions or Medicare samples, lacking generalizability to the larger shoulder
      arthroplasty population. QUESTIONS/PURPOSES: We sought to identify (1) patient
      specific risk factors for deep infection, and (2) the pathogen profile after
      primary shoulder arthroplasty in a large integrated healthcare system. METHODS: A
      retrospective cohort study was conducted. Of 4528 patients identified, 320 had
      died and 302 were lost to followup. The remaining 3906 patients had a mean
      followup of 2.7 years (1 day-7 years). The study endpoint was the diagnosis of
      deep infection, which was defined as revision surgery for infection supported
      clinically by more than one of the following criteria: purulent drainage from the
      deep incision, fever, localized pain or tenderness, a positive deep culture,
      and/or a diagnosis of deep infection made by the operating surgeon based on
      intraoperative findings. Risk factors evaluated included age, sex, race, BMI,
      diabetes status, American Society for Anesthesiologists (ASA) score, traumatic
      versus elective procedure, and type of surgical implant. For patients with deep
      infections, we reviewed the surgical notes and microbiology records for the
      pathogen profile. Multivariable Cox regression models were used to evaluate the
      association of risk factors and deep infection. Adjusted hazard ratios and 95% CI
      are presented. RESULTS: With every 1-year increase in age, a 5% (95% CI, 2%-8%)
      lower risk of infection was observed. Male patients had a risk of infection of
      2.59 times (95% CI, 1.27-5.31) greater than female patients. Patients undergoing
      primary reverse total shoulder arthroplasty had a 6.11 times (95% CI, 2.65-14.07)
      greater risk of infection compared with patients having primary unconstrained
      total shoulder arthroplasty. Patients having traumatic arthroplasties were 2.98
      times (95% CI, 1.15-7.74) more likely to have an infection develop than patients
      having elective arthroplasties. BMI, race, ASA score, and diabetes status were
      not associated with infection risk (all p > 0.05). Propionibacterium acnes was
      the most commonly cultured organism, accounting for 31% of isolates. CONCLUSIONS:
      Younger, male patients are at greater risk for deep infection after primary
      shoulder arthroplasty. Reverse total shoulder arthroplasty and traumatic shoulder
      arthroplasties also carry a greater risk for infection. Propionibacterium acnes
      was the most prevalent pathogen causing infection in our primary shoulder
      arthroplasty population. LEVEL OF EVIDENCE: Level II, prognostic study. See the
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24906813
TI  - Risk factors for the development of heterotopic ossification after acetabular
      fracture fixation.
AB  - BACKGROUND: Heterotopic ossification (HO) is a common complication of the
      operative treatment of acetabular fractures. Although the surgical approach has
      been shown to correlate with the development of ectopic bone, specific risk
      factors have not been elucidated. QUESTIONS/PURPOSES: The purposes of this study
      were to determine specific risk factors associated with the development of severe
      HO and the frequency with which patients develop severe HO after acetabular
      fracture fixation through an isolated Kocher-Langenbeck approach. METHODS: Using
      an institutional orthopaedic trauma database at a regional Level I trauma center,
      patients undergoing open treatment of acetabular fractures during the study
      period (January 2000 to January 2010) were identified. A review of medical
      records and imaging studies was performed on 508 patients who were treated by the
      senior author (MR) through an isolated Kocher-Langenbeck approach. During the
      study period, the senior author used indomethacin for HO prophylaxis in patients
      who had ipsilateral femur fracture treated with antegrade reamed medullary
      nailing or severe local soft tissue injury; 49 (10%) of the patients he treated
      with the Kocher-Langenbeck approach received prophylaxis, and they were excluded
      from this study, leaving a total of 459 patients who met inclusion criteria. Of
      those, 147 (29%) were lost to followup or did not have radiographs both before
      and at a minimum of 6 weeks (median, 1 week; range, 0-3 weeks), leaving 312 (61%
      of the patients treated with the Kocher-Langenbeck approach during this time)
      available for this analysis. Demographic data as well as information related to
      cause of injury, associated periacetabular findings, other system injuries, and
      treatment were gathered. Final followup radiographs were assessed for the
      presence of ectopic bone by two of the authors (TJO, AS) using the modified
      Brooker classification. Logistic regression was performed to identify possible
      predictors of development of severe ectopic bone. RESULTS: The only predictor we
      identified for the development of severe HO was the need for prolonged mechanical
      ventilation (odds ratio, 7.1; 95% confidence interval, 2.9-17.3; p=0.001). Injury
      Severity Score, sex, presence of comminution, femoral head impaction,
      dislocation, degloving injury, debris in the joint, number of other fractures,
      and head and chest Abbreviated Injury Score>2 did not correlate with severe HO.
      Severe HO (Brooker Class III or IV) developed in 38 of 312 patients (12%).
      CONCLUSIONS: Patients with prolonged mechanical ventilation might benefit from HO
      prophylaxis given the increased risk of developing severe HO in this patient
      population. However, future prospective studies need to be performed to verify
      this finding given the fact that a considerable number of patients were
      prophylactically treated in this study. LEVEL OF EVIDENCE: Level IV,
      prognosticstudy. See Guidelines for Authors for a complete description of levels
      of evidence.

PMID- 24906814
TI  - Novel external counterpulsation system, compact counterpulsation, was effective
      to treat severe ischemic heart failure: a case report.
AB  - Compact counterpulsation (CP) is a novel external counterpulsation system. The
      preoperative clinical utility of compact CP therapy in patients has not been
      established. In the present report, we describe a case wherein compact CP therapy
      was successfully used to treat severe ischemic heart failure. A 70-year-old man
      was diagnosed with ischemic heart disease and mitral valve regurgitation at 61
      years of age. Therefore, he underwent coronary artery bypass and mitral valve
      plasty. The patient's condition started to gradually deteriorate at 68 years of
      age, and he became progressively dependent on catecholamine support. Mitral valve
      regurgitation recurred, which caused worsening of heart function. Before a mitral
      valve replacement, the patient had been treated with compact CP therapy to
      improve heart function and general condition. The patient's clinical condition
      improved with compact CP therapy after only ten sessions; in addition, he could
      be weaned off catecholamine support. No adverse effects were observed, and
      therefore, he could complete the CP therapy as an outpatient. Mitral valve
      replacement was performed after a total of 44 sessions. The patient had an
      uneventful postoperative course and was discharged on the 18th postoperative day.
      Compact CP therapy was thus performed on our patient without any discomfort and
      appears to be an effective treatment for patients with severe ischemic heart
      failure. 

PMID- 24906815
TI  - Comparative genetic mapping and genomic region collinearity analysis of the
      powdery mildew resistance gene Pm41.
AB  - KEY MESSAGE: By applying comparative genomics analyses, a high-density genetic
      linkage map narrowed the powdery mildew resistance gene Pm41 originating from
      wild emmer in a sub-centimorgan genetic interval. Wheat powdery mildew, caused by
      Blumeria graminis f. sp. tritici, results in large yield losses worldwide. A high
      density genetic linkage map of the powdery mildew resistance gene Pm41,
      originating from wild emmer (Triticum turgidum var. dicoccoides) and previously
      mapped to the distal region of chromosome 3BL bin 0.63-1.00, was constructed
      using an F5:6 recombinant inbred line population derived from a cross of durum
      wheat cultivar Langdon and wild emmer accession IW2. By applying comparative
      genomics analyses, 19 polymorphic sequence-tagged site markers were developed and
      integrated into the Pm41 genetic linkage map. Ultimately, Pm41 was mapped in a
      0.6 cM genetic interval flanked by markers XWGGC1505 and XWGGC1507, which
      correspond to 11.7, 19.2, and 24.9 kb orthologous genomic regions in
      Brachypodium, rice, and sorghum, respectively. The XWGGC1506 marker co-segregated
      with Pm41 and could be served as a starting point for chromosome landing and map
      based cloning as well as marker-assisted selection of Pm41. Detailed comparative
      genomics analysis of the markers flanking the Pm41 locus in wheat and the
      putative orthologous genes in Brachypodium, rice, and sorghum suggests that the
      gene order is highly conserved between rice and sorghum. However, intra
      chromosome inversions and re-arrangements are evident in the wheat and
      Brachypodium genomic regions, and gene duplications are also present in the
      orthologous genomic regions of Pm41 in wheat, indicating that the Brachypodium
      gene model can provide more useful information for wheat marker development.

PMID- 24906816
TI  - Redo coronary artery bypass grafting.
AB  - Redo coronary artery bypass grafting (CABG) is more challenging than primary CABG
      in many aspects. Patients who undergo redo CABG are older, more comorbid, and
      with more sclerotic coronary and noncardiac arteries than seen in primary CABG.
      Operative procedures are more complicated, reentry of the sternum is sometimes
      problematic, and dissection of the heart is needed. If patent vein grafts are
      diseased, they can be sources of thromboembolism, and the patent left internal
      thoracic artery (ITA) anastomosed to the left anterior descending artery (LAD)
      must not be injured. The number of redo CABG procedures has been decreasing,
      because of frequent use of ITA to the LAD in primary CABG, aggressive
      percutaneous coronary intervention (PCI) by interventional cardiologists, and
      optimal medical therapy after primary CABG. In-hospital mortality in redo CABG is
      two to five times higher than that of primary CABG, although outcomes have been
      improving in recent years despite the patients' more comorbid background. Long
      term survival after redo CABG is comparable to that of PCI. The indication for
      redo CABG should be limited to patients who have jeopardized LAD territory, which
      is viable. CABG is also preferable to PCI in patients with more diseased vein
      grafts and low cardiac function. Various technical refinements have also improved
      the surgical results of redo CABG. Retrograde cardioplegia greatly contributed to
      proper myocardial protection, especially when the occluded coronary arteries are
      supplied by patent in situ arterial grafts. The off-pump technique has been used
      in redo CABG and may be beneficial in a selected, more comorbid population. 

PMID- 24906817
TI  - Simultaneous retention of thermostability and specific activity in chimeric human
      alkaline phosphatases.
AB  - Alkaline phosphatases (APs) are a family of dimeric metalloenzymes that has been
      utilized in many areas due to its ability to hydrolyze a variety of
      phosphomonoesters. While mammalian APs have higher specific activity than
      prokaryotic APs, they are generally less thermostable. To cultivate the
      possibility to confer mammalian APs with higher thermostability as well as high
      activity, we focused on human AP isozymes. Among the four isozymes of human APs,
      placental AP (PLAP) retains the highest thermostability, while intestinal AP
      (IAP) has the highest specific activity. Since the two APs display high homology,
      a series of chimeric enzymes were made in a secreted form to analyze their
      properties. Surprisingly, chimeric APs with IAP residues at the N-terminal and
      PLAP residues at the C-terminal regions showed higher specific activity than
      PLAP, while keeping thermostability as high as PLAP. Especially, one showed
      similar specific activity to IAP, while showing slower inactivation than PLAP
      after incubation at 75 degrees C. Interestingly, the mutant also showed higher
      resistance to uncompetitive inhibitors Phe and Leu than their parent enzymes,
      possibly due to increased hydrophilicity of the active site entrance residues.
      The obtained chimera will be useful as a novel reporter in various assays
      including gene hybridization.

PMID- 24906818
TI  - Fingolimod in a patient with heart failure on the background of pulmonary
      arterial hypertension and coronary artery disease.
AB  - BACKGROUND: Fingolimod is the first oral immunomodulatory therapy approved for
      highly active relapsing remitting multiple sclerosis. Based on the distribution
      pattern of fingolimod interacting sphingosine-1-phosphat receptors in organism
      including immune system and cardiovascular system clinical monitoring of patients
      and evaluation of adverse events are recommended. Despite extensive data on
      cardiovascular safety, experience with fingolimod in patients with concomitant
      cardiological disease, especially within the pulmonary circulation, is rare. CASE
      PRESENTATION: We report the case of a 46-year-old woman presented with relapsing
      remitting multiple sclerosis and severe idiopathic pulmonary arterial
      hypertension. Fingolimod was initiated because of disease activity of multiple
      sclerosis with two relapses and gadolinium-enhancing lesions in MRI. The patient
      demonstrated stable disease course of idiopathic pulmonary arterial hypertension
      when fingolimod was started. Fingolimod therapy did not alter or even worsen the
      pulmonary or cardiovascular conditions during first dose application as well as
      follow up of nine months. CONCLUSION: In this report, we present the first case
      of fingolimod treatment in a patient with highly active multiple sclerosis and
      severe idiopathic pulmonary arterial hypertension. We suggest an
      interdisciplinary approach with detailed cardiopulmonary monitoring for safety in
      such patients.

PMID- 24906819
TI  - A single aspergillus fumigatus intracranial abscess in an immunocompetent patient
      with parietal lobe tumorectomy.
AB  - Aspergillosis of the central nervous system is a rare fungal infection that is
      mainly reported in patients with immune deficiency, such as AIDS patients and
      organ transplant patients treated with immunosuppressive agents, and is uncommon
      among patients with intact immune function. We report here a rare case of
      intracranial aspergillosis in a patient who had previously undergone a parietal
      lobe tumorectomy. Aspergillus fumigatus was confirmed by histopathology, and
      susceptibility tests reported that this infection should respond to voriconazole.
      We believe the immunosuppression resulting from surgical trauma and
      glucocorticosteroid treatment may be contributing to the infection, and therefore
      management of these two factors may improve the prognosis. 

PMID- 24906820
TI  - Individual differences in perceptions of gay men's sexual role preferences from
      facial cues.
AB  - Research has demonstrated that the sexual role preferences of gay men can be
      perceived with accuracies that exceed chance guessing from viewing photos of
      their faces. This research was conducted with only heterosexual perceivers making
      the categorizations. We therefore examined whether men who have sex with men (N =
      121) were able to perceive sexual role preferences from faces and, critically,
      whether perceivers' masculinity, femininity, homonegativity, and own sexual role
      preference affected their categorizations of targets as "tops" or "bottoms." We
      found that men who have sex with men, like heterosexual perceivers in prior work,
      perceived gay men's sexual role preferences accurately. Furthermore, men who self
      identified with a receptive (bottom) role were more accurate in their
      categorizations and male perceivers who self-reported higher levels of
      masculinity were more likely to categorize other men as bottoms. These findings
      suggest that men's masculinity could serve as a lens through which people
      perceive others and interact with the world.

PMID- 24906821
TI  - Overexpression of alpha (1,6) fucosyltransferase associated with aggressive
      prostate cancer.
AB  - Aberrant protein glycosylation is known to be associated with the development of
      cancers. The aberrant glycans are produced by the combined actions of changed
      glycosylation enzymes, substrates and transporters in glycosylation synthesis
      pathways in cancer cells. To identify glycosylation enzymes associated with
      aggressive prostate cancer (PCa), we analyzed the difference in the expression of
      glycosyltransferase genes between aggressive and non-aggressive PCa. Three
      candidate genes encoding glycosyltransferases that were elevated in aggressive
      PCa were subsequently selected. The expression of the three candidates was then
      further evaluated in androgen-dependent (LNCaP) and androgen-independent (PC3)
      PCa cell lines. We found that the protein expression of one of the
      glycosyltransferases, alpha (1,6) fucosyltransferase (FUT8), was only detected in
      PC3 cells, but not in LNCaP cells. We further showed that FUT8 protein expression
      was elevated in metastatic PCa tissues compared to normal prostate tissues. In
      addition, using tissue microarrays, we found that FUT8 overexpression was
      statistically associated with PCa with a high Gleason score. Using PC3 and LNCaP
      cells as models, we found that FUT8 overexpression in LNCaP cells increased PCa
      cell migration, while loss of FUT8 in PC3 cells decreased cell motility. Our
      results suggest that FUT8 may be associated with aggressive PCa and thus is
      potentially useful for its prognosis. 

PMID- 24906823
TI  - Bergmann Glia are Patterned into Topographic Molecular Zones in the Developing
      and Adult Mouse Cerebellum.
AB  - Cerebellar circuits are patterned into an array of topographic parasagittal
      domains called zones. Zones are best revealed by gene expression, circuit
      anatomy, and cellular degeneration patterns. Thus far, the study of zones has
      been focused heavily on how neurons are organized. Because of this, detailed
      neuronal patterning maps have been established for Purkinje cells, granule cells,
      Golgi cells, unipolar brush cells, and also for the terminal field organization
      of climbing fiber and mossy fiber afferents. In comparison, however, it remains
      poorly understood if glial cells are also organized into zones. We have
      identified an Npy-Gfp BAC transgenic mouse line (Tau-Sapphire Green fluorescent
      protein (Gfp) is under the control of the neuropeptide Y (Npy) gene regulatory
      elements) that can be used to label Bergmann glial cells with Golgi-like
      resolution. In these adult transgenic mice, we found that Npy-Gfp expression was
      localized to Bergmann glia mainly in lobules VI/VII and IX/X. Using double
      immunofluorescence, we show that in these lobules, Npy-Gfp expression in the
      Bergmann glia overlaps with the pattern of the small heat shock protein HSP25, a
      Purkinje cell marker for zones located in lobules VI/VII and IX/X. Developmental
      analysis starting from the day of birth showed that HSP25 and Npy-Gfp expression
      follow a similar program of spatial and temporal patterning. However, loss of Npy
      signaling did not alter the patterning of Purkinje cell zones. We conclude that
      Bergmann glial cells are zonally organized and their patterns are restricted by
      boundaries that also confine cerebellar neurons into a topographic circuit map.

PMID- 24906825
TI  - Long-term microphytoplankton variability patterns using multivariate analyses:
      ecological and management implications.
AB  - Microphytoplankton data along the southern Tunisian coasts have been monitored
      weekly since 1995. This study used the data collected during the period 2000-2007
      to determine the temporal variability patterns and to characterize the
      geographical structures of microphytoplankton populations. The methodological
      approach consisted in isolating the temporal variability common to all sampled
      sites and in analyzing the "residual" site-specific component. Multivariate
      ordination methods were used to determine the seasonal and interannual
      variability. The temporal pattern shared by all sites was highlighted and the
      seasonal cycle of the most frequent phytoplankton communities contrasted the
      diatoms winter-spring species to the dinoflagellates summer-fall species.
      Multitable comparison allowed the identification of three areas exhibiting
      similar phytoplankton population variability. The results, despite the coastal
      location of sampling sites, indicated that hydrodynamic and geomorphologic
      properties of the different areas as well as anthropogenic activities play a key
      role in the structure of the phytoplankton communities. 

PMID- 24906824
TI  - Comprehensive study of early features in spinocerebellar ataxia 2: delineating
      the prodromal stage of the disease.
AB  - The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically
      studied. Main findings come from a homogeneous SCA type 2 (SCA2) population
      living in Cuba. The aim of this study was to characterize extensively the
      prodromal phase of SCA2 by several approaches. Thirty-seven non-ataxic SCA2
      mutation carriers and its age- and sex-matched controls underwent clinical
      assessments, including standardized neurological exam, structured interviews and
      clinical scales, and looking for somatic and autonomic features, as well as a
      neuropsychological battery, antisaccadic recordings, and MRI scans. Main clinical
      somatic features of non-ataxic mutation carriers were cramps, sensory symptoms,
      sleep disorders, and hyperreflexia, whereas predominating autonomic symptoms were
      pollakiuria/nocturia, constipation, and frequent throat clearing. Cognitive
      impairments included early deficits of executive functions and visual memory,
      suggesting the involvement of cerebro-cerebellar-cerebral loops and/or reduced
      cholinergic basal forebrain input to the cortex. Antisaccadic task revealed
      impaired oculomotor inhibitory control but preserved ability for error
      correction. Cognitive and antisaccadic deficits were higher as carriers were
      closer to the estimated onset of ataxia, whereas higher Scale for the Assessment
      and Rating of Ataxia (SARA) scores were associated most notably to vermis
      atrophy. The recognition of early features of SCA2 offers novel insights into the
      prodromal phase and physiopathological base of the disease, allowing the
      assessment of its progression and the efficacy of treatments, in particular at
      early phases when therapeutical options should be most effective. 

PMID- 24906822
TI  - Ambulatory hypertension subtypes and 24-hour systolic and diastolic blood
      pressure as distinct outcome predictors in 8341 untreated people recruited from
      12 populations.
AB  - BACKGROUND: Data on risk associated with 24-hour ambulatory diastolic (DBP24)
      versus systolic (SBP24) blood pressure are scarce. METHODS AND RESULTS: We
      recorded 24-hour blood pressure and health outcomes in 8341 untreated people
      (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We
      computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over
      11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from
      cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal
      cardiovascular event. Isolated diastolic hypertension (DBP24>=80 mm Hg) did not
      increase the risk of total mortality, cardiovascular mortality, or stroke
      (HRs<=1.54; P>=0.18), but was associated with a higher risk of fatal combined
      with nonfatal cardiovascular, cardiac, or coronary events (HRs>=1.75; P<=0.0054).
      Isolated systolic hypertension (SBP24>=130 mm Hg) and mixed diastolic plus
      systolic hypertension were associated with increased risks of all aforementioned
      end points (P<=0.0012). Below age 50, DBP24 was the main driver of risk, reaching
      significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular
      mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined
      (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR<=0.92;
      P>=0.068); above age 50, SBP24 predicted all end points (HR>=1.19; P<=0.0002)
      with a nonsignificant contribution of DBP24 (0.96<=HR<=1.14; P>=0.10). The
      interactions of age with SBP24 and DBP24 were significant for all cardiovascular
      and coronary events (P<=0.043). CONCLUSIONS: The risks conferred by DBP24 and
      SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary
      complications below age 50, whereas above age 50 SBP24 and isolated systolic and
      mixed hypertension are the predominant risk factors.

PMID- 24906827
TI  - Potential source apportionment of polycyclic aromatic hydrocarbons in surface
      sediments from the middle and lower reaches of the Yellow River, China.
AB  - In this work, principal component analysis/multiple linear regression (PCA/MLR),
      positive matrix factorization (PMF), and UNMIX model were employed to apportion
      potential sources of polycyclic aromatic hydrocarbons (PAHs) in surface sediments
      from middle and lower reaches of the Yellow River, based on the measured PAHs
      concentrations in sediments collected from 22 sites in November 2005. The results
      suggested that pyrogenic sources were major sources of PAHs. Further analysis
      indicated that source contributions of PAHs compared well among PCA/MLR, PMF, and
      UNMIX. Vehicles contributed 25.1-36.7 %, coal 34.0-41.6 %, and biomass burning
      and coke oven 29.2-33.2 % of the total PAHs, respectively. Coal combustion and
      traffic-related pollution contributed approximately 70 % of anthropogenic PAHs to
      sediments, which demonstrated that energy consumption was a predominant factor of
      PAH pollution in middle and lower reaches of the Yellow River. In addition, the
      distributions of contribution for each identified source category were studied,
      which showed similar distributed patterns for each source category among the
      sampling sites.

PMID- 24906826
TI  - Rapid biological synthesis of silver nanoparticles using Leucas martinicensis
      leaf extract for catalytic and antibacterial activity.
AB  - A novel green approach for the synthesis and stabilization of silver
      nanoparticles (AgNPs) using water extract of Leucas martinicensis leaf has been
      developed. As obtained, the nanoparticles are characterized by UV-visible (UV
      Vis), transmission electron microscope (TEM), and X-ray diffraction (XRD). The
      crystalline nature of the AgNPs is confirmed by the prominent peaks in the XRD
      pattern. FTIR spectra suggest that the possible biomolecules are responsible for
      the efficient stabilization of the sample. The effects of leaf quantity on the
      biosynthesis of AgNPs are investigated by UV-Vis spectrophotometer. The
      synthesized AgNPs are observed to have a good catalytic activity on the reduction
      of methylene blue by L. martinicensis leaf. This is confirmed by the decrease in
      absorbance maximum values of methylene blue with respect to time through UV-Vis
      spectrophotometer. Moreover, the antibacterial activity of synthesized AgNPs
      against Staphylococcus aureus, Bacillus subtilis, Salmonella typhi, and
      Escherichia coli are screened.

PMID- 24906828
TI  - A review on management of chrome-tanned leather shavings: a holistic paradigm to
      combat the environmental issues.
AB  - Raw hide/skins come to the tanners as a by-product of meat industry which is
      converted into value-added leather as product for fashion market. Leather
      manufacturing is a chemical process of natural biological matrix. It employs a
      huge quantity of water and inorganic and organic chemicals for processing and
      thereby discharges solid and liquid wastes into the environment. One of the
      potential solid wastes generated from leather industry is chrome-tanned leather
      shavings (CTLSs), and its disposal is increasingly becoming a huge challenge on
      disposal to tanners due to presence of heavy metal chromium. Hence, finding a
      sustainable solution to the CTLS disposal problem is a prime challenge for global
      tanners and researchers. This paper aims to the deeper review of various disposal
      methods on CTLS such as protein, chromium, and energy recovery processes and its
      utilization methodologies. Sustainable technologies have been developed to
      overcome CTLS solid wastes emanating from leather processing operations. Further,
      this review paper brings a broader classification of developed methodologies for
      treatment of CTLSs. 

PMID- 24906829
TI  - Methodology for technical and economic assessment of advanced routes for sludge
      processing and disposal.
AB  - In order to meet the environmental legislative framework in force in Europe and
      reduce sludge processing and disposal costs, several sludge treatment
      technologies and management strategies have been proposed in the last two
      decades. The evaluation of their technical and economic suitability, case by
      case, may be a challenge, since many aspects are involved, so that a robust
      decision support system should be used. Within the ROUTES project (founded within
      the EU Seventh Framework Programme), the authors have developed an assessment
      procedure which allows rating several technical factors (such as system
      reliability, complexity, safety aspects, modularity, etc.) and estimating capital
      and operating costs, in case a plant is being upgraded. The comparison between
      the original (reference) plant and the modified configuration informs about
      technical hot spots (which are expressed by a traffic light-type colour code) and
      cost gaps resulting from the implementation of the new solution. 

PMID- 24906830
TI  - Electrochemical oxidation of ampicillin antibiotic at boron-doped diamond
      electrodes and process optimization using response surface methodology.
AB  - Electrochemical oxidation and process optimization of ampicillin antibiotic at
      boron-doped diamond electrodes (BDD) were investigated in a batch electrochemical
      reactor. The influence of operating parameters, such as ampicillin concentration,
      electrolyte concentration, current density, and reaction temperature, on
      ampicillin removal, COD removal, and energy consumption was analyzed in order to
      optimize the electrochemical oxidation process under specified cost-driven
      constraints using response surface methodology. Quadratic models for the
      responses satisfied the assumptions of the analysis of variance well according to
      normal probability, studentized residuals, and outlier t residual plots. Residual
      plots followed a normal distribution, and outlier t values indicated that the
      approximations of the fitted models to the quadratic response surfaces were very
      good. Optimum operating conditions were determined at 618 mg/L ampicillin
      concentration, 3.6 g/L electrolyte concentration, 13.4 mA/cm(2) current density,
      and 36  degrees C reaction temperature. Under response surface optimized
      conditions, ampicillin removal, COD removal, and energy consumption were obtained
      as 97.1 %, 92.5 %, and 71.7 kWh/kg CODr, respectively.

PMID- 24906831
TI  - Bio-beads with immobilized anaerobic bacteria, zero-valent iron, and active
      carbon for the removal of trichloroethane from groundwater.
AB  - Chlorinated hydrocarbons are the most common organic pollutants in groundwater
      systems worldwide. In this study, we developed bio-beads with immobilized
      anaerobic bacteria, zero-valent iron (ZVI), and activated carbon (AC) powder and
      evaluated their efficacy in removing 1,1,1-trichloroethane (TCA) from
      groundwater. Bio-beads were produced by polyvinyl alcohol, alginate, and AC
      powder. We found that the concentration of AC powder used significantly affected
      the mechanical properties of immobilized bio-beads and that 1.0 % (w/v) was the
      optimal concentration. The bio-beads effectively degraded TCA (160 mg L(-1)) in
      the anaerobic medium and could be reused up to six times. The TCA degradation
      rate of bio-beads was 1.5 and 2.3 times greater, respectively, than ZVI + AC
      treatment or microbes + AC treatment. Measuring FeS produced by microbial
      reactions indicated that TCA removal occurred via FeS-catalyzed dechlorination.
      Analysis of clonal libraries derived from bio-beads demonstrated that the
      dominant species in the community were Betaproteobacteria and
      Gammaproteobacteria, which may contribute to the long-term stability of ZVI
      reactivity during TCA dechlorination. This study shows that the combined use of
      immobilized anaerobic bacteria, ZVI, and AC in bio-beads is effective and
      practical for TCA dechlorination and suggests they may be applicable towards
      developing a groundwater treatment system for the removal of TCA.

PMID- 24906832
TI  - Innovative two-stage mesophilic/thermophilic anaerobic degradation of sonicated
      sludge: performances and energy balance.
AB  - This study investigates for the first time, on laboratory scale, the possible
      application of an innovative enhanced stabilization process based on sequential
      mesophilic/thermophilic anaerobic digestion of waste-activated sludge, with low
      energy sonication pretreatment. The first mesophilic digestion step was conducted
      at short hydraulic retention time (3-5 days), in order to favor volatile fatty
      acid production, followed by a longer thermophilic step of 10 days to enhance the
      bioconversion kinetics, assuring a complete pathogen removal. The high volatile
      solid removals, up to 55%, noticeably higher compared to the performances of a
      single-stage process carried out in same conditions, can guarantee the stability
      of the final digestate for land application. The ultrasonic pretreatment
      influenced significantly the fatty acid formation and composition during the
      first mesophilic step, improving consequently the thermophilic conversion of
      these compounds into methane. Methane yield from sonicated sludge digestion
      reached values up to 0.2 Nm(3)/kgVSfed. Positive energy balances highlighted the
      possible exploitation of this innovative two-stage digestion in place of
      conventional single-stage processes.

PMID- 24906833
TI  - Treatment of pretreated coking wastewater by flocculation, alkali out, air
      stripping, and three-dimensional electrocatalytic oxidation with parallel plate
      electrodes.
AB  - The coking wastewater generally comprises highly concentrated, recalcitrant, and
      toxic organic pollutants, so its treatment has been of great importance to
      prevent living beings and their environment from these hazardous contaminations.
      The treatment of pretreated coking wastewater by flocculation-coagulation, alkali
      out, air stripping, and three-dimensional (3-D) electrocatalytic oxidation was
      performed (gap between the used beta-PbO2/Ti anode and titanium cathode, 12 mm;
      mass ratio of Cu-Mn/granular activated carbon (GAC) to effluent, 1:4; cell
      voltage, 7 V). The results showed that the pH adjusting from 3.7 to 6.1 was
      necessary for coagulants; alkali out played an important role because it brought
      up precipitation containing higher fatty acids as well as other contaminants to
      decrease the chemical oxygen demand (COD) in the effluent, and it had also forced
      the reduction of ammonia nitrogen (NH3-N) by incorporating with air stripping;
      for 3-D electrocatalytic oxidation with a bleaching liquid assisting, the initial
      pH 8.5 of effluent was suitable for Cu-Mn/GAC; moreover, it was considered that
      its Cu component was dedicated to the decrease of COD and NH3-N, while the Mn
      component specialized in the decay of NH3-N. The residual COD and NH3-N values in
      the final effluent with pH 6.5 were 95.8 and 8.8 mg/L, respectively,
      demonstrating that the whole processes applied were feasible and low in cost.

PMID- 24906835
TI  - Prevalence and antimicrobial susceptibility of Salmonella spp. in small Indian
      mongooses (Herpestes auropunctatus) in Grenada, West Indies.
AB  - Intestinal samples from 156 small Indian mongooses (Herpestes auropunctatus)
      collected island-wide in Grenada from April 2011 to March 2013 were examined for
      the presence of Salmonella enterica spp. Nineteen (12%) mongooses were culture
      positive for S. enterica spp. of which five serotypes were identified. Salmonella
      javiana and S. Montevideo were the most commonly isolated serotypes. The other
      serotypes isolated were S. Rubislaw, S. Panama and S. Arechavaleta. All isolates
      were susceptible to amoxicillin-clavulanic acid, ampicillin, cefotaxime,
      ceftazidime, ciprofloxacin, enrofloxacin, gentamicin, nalidixic acid, imipenem
      and trimethoprim-sulfamethoxazole. One isolate (S. Montevideo) showed resistance
      to tetracycline and intermediate resistance to streptomycin. The five isolated
      Salmonella serotypes are potential human pathogens suggesting that the mongoose
      may play a role in the epidemiology of human salmonellosis in Grenada.

PMID- 24906834
TI  - Assessment of genotoxic effects of lead in occupationally exposed workers.
AB  - The genotoxicological effects in 200 lead acid storage battery recycling and
      manufacturing industry workers in Hyderabad along with matched 200 controls were
      studied. The genetic damage was determined by comet, micronucleus (MN), and
      chromosomal aberration (CA) test in peripheral blood lymphocytes (PBL). The MN
      test was also carried out in buccal epithelial cells (BECs). Pb in ambient air,
      blood Pb (B-Pb) concentrations, and hematological parameters were measured. The
      superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione
      peroxidase (GPx), and malondialdehyde (MDA) formed were also studied. The results
      of the present study showed that there was a statistically significant (P < 0.01)
      increase in mean percent tail DNA, frequency of CA, and MN in PBL as well as in
      BEC as compared to controls. Pb in ambient air and B-Pb concentrations were found
      to be significantly higher (P < 0.01). The hematocrit, hemoglobin, and red blood
      cell values were significantly lowered in Pb-exposed workers in comparison to
      controls. SOD, GPx, and CAT levels were significantly decreased while GSH and MDA
      levels increased in exposed group when compared to control group. The present
      study suggests that environmental health standards should be enforced to control
      Pb contamination from battery industries to reduce human health risk.

PMID- 24906836
TI  - Effectiveness of combinations of Ayurvedic drugs in alleviating drug toxicity and
      improving quality of life of cancer patients treated with chemotherapy.
AB  - PURPOSE: This study was conducted to assess the effectiveness of combinations of
      Ayurvedic drugs in alleviating the toxicity of chemotherapy and improving the
      quality of life of cancer patients. The following was the research question: Can
      Ayurvedic drugs be used to alleviate the side effects of chemotherapy and improve
      the quality of life of cancer patients? METHOD: Random patients with malignancies
      of different tissues, grades, and stages were divided into two groups according
      to their treatment modality. Group 1 consisted of 15 patients treated with six
      cycles of chemotherapy alone and who did not receive any Ayurvedic drugs (control
      group). Group 2 consisted of patients (divided into three arms) who received
      Ayurvedic drugs during chemotherapy and after chemotherapy. Nineteen patients in
      arm 1 received the Ayurvedic drugs Mauktikyukta Kamdudha (MKD) and Mauktikyukta
      Praval Panchamruta (MPP) along with a full course of chemotherapy. Fifteen
      patients in arm 2 received the same Ayurvedic treatment, but the treatment was
      started after completing the sixth cycle of chemotherapy. Eighteen patients in
      arm 3 received the Suvarnabhasmadi formulation (SBD) in addition to MKD and MPP
      after completing the sixth cycle of chemotherapy. Treatment was given for 16
      weeks in all three arms. Patients from both groups were observed for a period of
      6 months. The assessment criteria depended on Common Toxicity Criteria (CTC
      designed by NIH and NCI): haemogram; weight; physical examination including
      Quality of Life Questionnaire (QLQ designed by the European Organization of
      Research and Treatment of Cancer (EORTC)) for functional, symptom and global
      scores; and Karnofsky score for assessment of general well-being and activities
      of daily life. ECOG (Eastern Cooperation Oncology Group) score was also
      additionally included for assessment of symptoms. RESULTS: From amongst the
      symptomatic criteria, there was significant improvement in all the three arms
      compared with the control group in nausea, loss of appetite, constipation, and
      fatigue. There was significant improvement in the Karnofsky score and global
      score of the QLQ, which in fact incorporate symptomatic criteria, general
      condition, functional ability and disease-related symptoms. These significant
      differences were observed in group 2 (arms 1, 2, 3) in comparison with group 1
      (control), in spite of the fact that in arms 2 and 3, the Ayurvedic treatment was
      started after completion of chemotherapy. The haemogram did not show a
      significant difference between the control and the three arms of group 2.
      CONCLUSION: Adjunct treatment with herbo-mineral and metallic Ayurvedic drugs
      appears to have a significant effect on reducing the toxic side effects of
      chemotherapy drugs in cancer patients. Our preliminary data suggests that
      Ayurvedic treatment should be given simultaneously from the beginning of
      chemotherapy to have the desired effect. However, there is a need to extend this
      work by conducting a well-planned two-armed study on cancer patients with defined
      cancer sites with selected Ayurvedic drug combinations, and observing the
      patients for a longer period of time to confirm the effectiveness of Ayurvedic
      drugs in reducing the side effects of chemotherapy.

PMID- 24906837
TI  - Interventions for preparing patients for chemotherapy and radiotherapy: a
      systematic review.
AB  - PURPOSE: Undergoing chemotherapy and radiotherapy can be physically and
      psychologically stressful for people with cancer. Providing preparatory
      information to cancer patients as they face treatment and its aftermath has the
      potential to improve patient outcomes. This study assessed the methodological
      quality and effectiveness of interventions providing preparatory information
      about chemotherapy and/or radiotherapy to cancer patients in improving patient
      outcomes and health care use. METHODS: MEDLINE, EMBASE, and Cochrane databases
      were systematically searched from January 1995 until October 2012. INCLUSION
      CRITERIA: (1) met Effective Practice and Organisation of Care (EPOC) criteria for
      study design; (2) included adults with a current cancer diagnosis; (3) delivered
      preparatory information via a health care provider or was self-directed; (4)
      examined psychological well-being, quality of life, physical symptoms,
      satisfaction, knowledge, or health service utilisation. Studies were assessed for
      methodological quality using the EPOC criteria. RESULTS: Eighteen studies
      involving 3,443 cancer patients met inclusion criteria. Interventions included
      written information, audiotapes, videotapes, and computer programs. Interventions
      improved patient satisfaction (6/7 studies), information needs and patient
      knowledge (5/6 studies), physical symptoms (3/4 studies) and cost (1/1 study).
      More than half of the interventions improved psychological outcomes and quality
      of life (10/17 studies). CONCLUSION: Providing preparatory information can
      improve patient-reported outcomes in cancer patients undergoing chemotherapy and
      radiotherapy, especially with respect to satisfaction and knowledge. Some, but
      not all, studies improved psychological outcomes and physical symptoms. There is
      a need for methodologically rigorous research to determine the most effective
      timing and method of delivery of preparatory information to improve patient
      outcomes.

PMID- 24906839
TI  - Physical activity, daily walking, and lower limb lymphedema associate with
      physical function among uterine cancer survivors.
AB  - PURPOSE: We sought to quantify the proportion of uterine cancer survivors who
      self-report poor physical function. We then sought to quantify the association of
      poor physical function with physical activity (PA), walking, and lower limb
      lymphedema (LLL), among women with a history of uterine cancer. METHODS: Physical
      function was quantified using the Medical Outcomes Study 12-Item Short-Form
      Health Survey (SF-12) questionnaire. PA, walking, and LLL were measured using
      self-report questionnaire. PA was calculated using metabolic equivalent hours per
      week (MET-h week(-1)), and walking was calculated using blocks per day (blocks
      day(-1)). Logistic regression estimated odds ratios (OR) and 95 % confidence
      intervals (95 % CI). RESULTS: Among the 213 uterine cancer survivors in our
      survey (43 % response rate), 35 % self-reported poor physical function. Compared
      to participants who reported <3.0 MET-h week(-1) of PA, participants who reported
      >=18.0 MET-h week(-1) of PA were less likely to have poor physical function (OR
      0.03, 95 % CI 0.01-0.10; P trend  < 0.0001). Compared to participants who
      reported <4.0 blocks day(-1) of walking, participants who reported >=12.0 blocks
      day(-1) of walking were less likely to have poor physical function (OR 0.07, 95 %
      CI 0.03-0.19; P trend  < 0.0001). Compared to participants who did not have LLL,
      participants with LLL were more likely to have poor physical function (OR 5.25,
      95 % CI 2.41-11.41; P < 0.0001). CONCLUSION: Higher levels of PA and walking
      associate with a lower likelihood of reporting poor physical function. The
      presence of LLL associates with a higher likelihood of reporting poor physical
      function. These findings are hypothesis-generating and should be evaluated in
      future prospective studies.

PMID- 24906838
TI  - Intensive nutritional counseling improves PG-SGA scores and nutritional symptoms
      during and after radiotherapy in Korean cancer patients.
AB  - PURPOSE: This study was conducted for the nutritional assessment of cancer
      patients undergoing radiotherapy (RT) and to investigate the changes in nutrition
      status, oral intake, morbidity and quality of life (QOL) in cancer patients after
      intensive nutrition counseling. METHODS: Eighty-seven cancer patients were
      randomized to either a nutrition counseling group (n = 44, age 58.0 +/- 2.2
      years) or a control group (n = 43, 62.0 +/- 1.8 years). Nutrition counseling
      accompanied RT, and the subjects received at least three sessions of
      individualized dietary counseling over the duration of RT. Assessment parameters
      were nutritional intake (24-h recall method), nutritional status Patient
      Generated Subjective Global Assessment (PG-SGA), QOL and blood parameters
      including albumin. All parameters were measured at baseline, at the end of RT,
      and 1 month after the termination of RT. RESULTS: Body weight, body mass index
      (BMI), and energy and protein intake for the intervention and control groups did
      not differ significantly between baseline and the end of RT. However, at 1 month
      follow-up, protein intake was significantly decreased in the control group (p <
      0.05). Blood albumin, total protein (TP), total lymphocyte count (TLC) were not
      different between the two groups. According to PG-SGA stage, at 1 month follow
      up, patients in the intervention group showed increased number of patients with
      stage A status (well nourished). In addition, insomnia and nausea was
      significantly improved in the intervention group assessed by QOL. CONCLUSION: We
      suggest that repetitive and intensive nutritional counseling is necessary to
      improve QOL and to prevent deterioration of nutritional status in cancer patients
      receiving RT.

PMID- 24906840
TI  - Cost comparison of open approach, transoral laser microsurgery and transoral
      robotic surgery for partial and total laryngectomies.
AB  - Activity-based costing is used to give a better insight into the actual cost
      structure of open, transoral laser microsurgery (TLM) and transoral robotic
      surgery (TORS) supraglottic and total laryngectomies. Cost data were obtained
      from hospital administration, personnel and vendor structured interviews. A
      process map identified 17 activities, to which the detailed cost data are
      related. One-way sensitivity analyses on the patient throughput, the cost of the
      equipment or operative times were performed. The total cost for supraglottic open
      (135-203 min), TLM (110-210 min) and TORS (35-130 min) approaches were 3,349 euro
      (3,193-3,499 euro), 3,461 euro (3,207-3,664 euro) and 5,650 euro (4,297-5,974
      euro), respectively. For total laryngectomy, the overall cost were 3,581 euro
      (3,215-3,846 euro) for open and 6,767 euro (6,418-7,389 euro) for TORS. TORS cost
      is mostly influenced by equipment (54%) where the other procedures are
      predominantly determined by personnel cost (about 45%). Even when we doubled the
      yearly case-load, used the shortest operative times or a calculation without
      robot equipment costs we did not reach cost equivalence. TORS is more expensive
      than standard approaches and mainly influenced by purchase and maintenance costs
      and the use of proprietary instruments. Further trials on long-term outcomes and
      costs following TORS are needed to evaluate its cost-effectiveness.

PMID- 24906841
TI  - Outcome measures in stapes surgery: postoperative results are independent from
      preoperative parameters.
AB  - The aim of this study was to compare audiometric results before and after stapes
      surgery and identify potential prognostic factors to appropriately select
      patients with otosclerosis who will most likely benefit from surgery. We enrolled
      126 patients with otosclerosis (162 consecutive ears) in our study who underwent
      stapes surgery between 2007 and 2012 at our institution. Preoperative and
      postoperative data including pure-tone audiometry, speech audiometry, stapedial
      reflex audiometry and surgical data were analyzed. The average preoperative air
      bone gap (ABG) was 28.9 +/- 8.6 dB. Male patients and patients older than 45
      years of age had greater preoperative ABGs in comparison to females and younger
      patients. Postoperative ABGs were 11.2 +/- 7.4 dB. The average ABG gain was 17.7
      +/- 11.1 dB. Preoperative audiometric data, age, gender and type of surgery did
      not influence the postoperative results. Stapes surgery offers predictable
      results independent from disease progression or patient-related factors. While
      absolute values of hearing improvement are instrumental in reflecting audiometric
      results of a cohort, relative values better reflect individual's audiometric data
      resembling the patient's benefit.

PMID- 24906842
TI  - Prognostic significance of lymph node ratio in patients with Merkel cell
      carcinoma.
AB  - Merkel cell carcinoma is a rare and aggressive metastasizing tumor of the skin.
      Lymph node metastasis is a significant clinical prognostic factor for overall and
      disease-free survival in patients with Merkel cell carcinoma. A retrospective
      medical chart review of 12 Merkel cell carcinoma patients was performed. All
      patients received treatment at the Medical University of Vienna and underwent
      lymph node dissection between 1994 and 2013. The lymph node ratio was determined
      by dividing the total number of positive lymph nodes by the entire number of
      dissected lymph nodes. A positive lymph node ratio was defined as a number >0 and
      the negative lymph node ratio was defined by zero. The median follow-up was 44
      months (range 4-92). A positive lymph node ratio (range 1.00-0.04) was found in 7
      (58%) out of 12 patients of whom 5 (71%) died of disease. A negative lymph node
      ratio was found in 5 (42%) out of 12 patients of whom 2 (40%) patients died of
      disease. The disease-specific death rate was higher in patients diagnosed with a
      positive lymph node ratio compared to patients diagnosed with a negative lymph
      node ratio. Based on these preliminary findings, there might be a prognostic
      impact of lymph node ratio in patients suffering from Merkel cell carcinoma.

PMID- 24906843
TI  - Role of panendoscopy in identifying and managing risk of head and neck squamous
      cell carcinoma in routine follow-up: a retrospective clinical evaluation.
AB  - We discuss the clinical effectiveness and predictive value of routine
      panendoscopy for surveillance and follow-up of head and neck squamous cell
      carcinoma (HNSCC). Retrospective comparative study. Department of Otolaryngology
      Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg,
      Germany. Two hundred and four HNSCC patients (follow-up between 2004 and 2007)
      were retrospectively evaluated. During follow-up, panendoscopy was performed
      routinely once a year. To avoid unnecessary procedures, we evaluated the value of
      radiological and clinical parameters in follow-up. On comparing normal
      computerized tomography (CT) vs. abnormal CT results, a 13-fold higher frequency
      of recurrence (odds ratio 12.74; 95% CI 4.22, 38.48; p < 0.001) was found.
      Additionally, patient medical history, clinical investigation, and recurrence
      pattern were significant parameters when detecting a possible recurrence.
      Panendoscopy could have been avoided in 40% of patients with HNSCC (173/432). A
      follow-up schedule avoiding routine panendoscopy in HNSCC follow-up when the
      combination of diagnostic parameters is satisfactory does not influence the
      sensitivity or specificity of the test.

PMID- 24906844
TI  - A modified intranasal endoscopic excision for nasal vestibular cyst in China.
AB  - This study aimed to improve the surgical removal procedure for nasal vestibular
      cysts. Twenty-three patients with nasal vestibular cysts underwent surgical
      removal of the cyst via a transoral sublabial approach and another 30 patients
      via a modified intranasal endoscopic excision method. The 30 patients were
      treated with local anesthesia and the roof of the cyst, which was firmly attached
      to the mucous membrane of the anterior floor of the nasal cavity, was removed
      transnasally with microdebrider. Bleeding of the opening was stopped by electric
      coagulation without nasal packing. Among the 30 consecutive patients who
      underwent the modified surgical procedure, all patients were successfully
      treated. The mean duration of surgery was 5.7 +/- 2.6 min. The mean estimated
      blood loss was 3.5 +/- 2.1 ml. All patients were outpatients. The mean hospital
      stay was 1 h. The mean total cost was <euro>140. The visual analog scale scores
      of postoperative pain, pressure and nasal obstruction were 1, 0 and 1,
      respectively. The incidence rate of postoperative lip swelling or numbness was 0
      %. Postoperative endoscopic findings revealed that the cyst was replaced by an
      air-containing sinus with a persistent opening at the anterolateral nasal floor.
      There was no recurrence during a mean follow-up of 18 months. The modified
      intranasal endoscopic excision is a simple, less invasive, low-cost and effective
      surgical procedure for the treatment of nasal vestibular cysts. It might change
      the pattern of treatment for nasal vestibular cysts in China.

PMID- 24906845
TI  - Increasing disability-free life expectancy among older adults in Palestine from
      2006 to 2010.
AB  - BACKGROUND: The population of Palestine comprises almost 200 000 Palestinians
      aged 60 or older. The purpose of the study was to estimate disability-free life
      expectancy for Palestinians living in the West Bank and Gaza Strip and to
      evaluate changes from 2006 to 2010. METHODS: The study combined mortality data
      and prevalence of activity limitation derived from the Palestinian Family Health
      Surveys carried out in 2006 and 2010. Based on questions about the ability to
      perform five basic daily activities, disability-free life expectancy was
      estimated. Changes between 2006 and 2010 were decomposed into contributions from
      changes in mortality and disability. RESULTS: Life expectancy at age 60 increased
      from 17.1 years in 2006 to 17.3 years in 2010 for men and from 18.7 years to 19.0
      years for women. Disability-free life expectancy increased significantly, by 1.3
      years for 60-year-old men (from 12.8 years to 14.1 years) and 1.8 years for 60
      year-old women (from 12.6 years to 14.4 years). This increase was seen in the
      Gaza Strip as well as in the West Bank. While the modest contribution of the
      mortality effect did not differ between gender and regions, the strong
      contributions from the disability effects varied, being greatest for women in the
      Gaza Strip. CONCLUSION: The significant increase in disability-free life
      expectancy for both genders is remarkable and, to our knowledge, not seen in
      other low-income countries. This change may be due to decreasing incidence of
      disability and greater recovery from disability as a result of better prevention,
      care and rehabilitation of chronic diseases.

PMID- 24906847
TI  - Prevalent burdensome mental disorders remain untreated for years: manifesto for
      early diagnosis and treatment.

PMID- 24906848
TI  - Using Breaking Bad to teach about defense mechanisms.
AB  - Defense mechanisms represent an important component of medical education that
      should be taught to all medical students, psychiatry residents, and other mental
      health trainees. Teaching about defense mechanisms can become more engaging by
      analyzing popular media. Using Breaking Bad, a well-known television show, we
      recommend specific scenes and episodes that can be used in teaching about defense
      mechanisms. 

PMID- 24906846
TI  - Under-estimation of obesity, hypertension and high cholesterol by self-reported
      data: comparison of self-reported information and objective measures from health
      examination surveys.
AB  - BACKGROUND: Non-communicable diseases (NCDs) cause 63% of deaths worldwide. The
      leading NCD risk factor is raised blood pressure, contributing to 13% of deaths.
      A large proportion of NCDs are preventable by modifying risk factor levels.
      Effective prevention programmes and health policy decisions need to be evidence
      based. Currently, self-reported information in general populations or data from
      patients receiving healthcare provides the best available information on the
      prevalence of obesity, hypertension, diabetes, etc. in most countries. METHODS:
      In the European Health Examination Survey Pilot Project, 12 countries conducted a
      pilot survey among the working-age population. Information was collected using
      standardized questionnaires, physical measurement and blood sampling protocols.
      This allowed comparison of self-reported and measured data on prevalence of
      overweight, obesity, hypertension, high blood cholesterol and diabetes. RESULTS:
      Self-reported data under-estimated population means and prevalence for health
      indicators assessed. The self-reported data provided prevalence of obesity four
      percentage points lower for both men and women. For hypertension, the self
      reported prevalence was 10 percentage points lower, only in men. For elevated
      total cholesterol, the difference was 50 percentage point among men and 44
      percentage points among women. For diabetes, again only in men, the self-reported
      prevalence was 1 percentage point lower than measured. With self-reported data
      only, almost 70% of population at risk of elevated total cholesterol is missed
      compared with data from objective measurements. CONCLUSIONS: Health indicators
      based on measurements in the general population include undiagnosed cases,
      therefore providing more accurate surveillance data than reliance on self
      reported or healthcare-based information only.

PMID- 24906849
TI  - Opioid needs of terminally ill patients with gynecologic malignancies.
AB  - BACKGROUND: Little is known about patterns and predictive factors regarding
      opioid use for terminally ill patients with gynecologic malignancies. The aim of
      this study was to elucidate predictors affecting opioid requirements of end-of
      life patients with gynecologic malignancies. METHODS: A retrospective study was
      carried out on patients with gynecological malignancies admitted to our institute
      and died during the years 2002 to 2012. The association between maximum opioid
      dose and factors affecting opioid requirements were examined. Data extracted from
      medical records included age, site of primary cancer, maximum total dose of
      opioids prescribed over 24 h, the site of recurrence and metastasis, procedures
      performed during the hospital stay, total number of chemotherapy courses and
      overall survival. RESULTS: The study identified 189 patients. Most patients had
      ovarian cancer (42.3 %) followed by cervical cancer (28.0 %) and then corpus
      malignancy (27.0 %). Opioid requirements decreased with increasing age,
      especially from the 50s onward. This was particularly marked in cervical cancer
      patients. In addition, pelvic metastasis was associated with the maximum dose of
      opioids and the average opioid use was highest in patients with cervical cancer.
      CONCLUSION: Young age and pelvic invasion were significant predictive factors
      regarding opioid requirements. Additionally, cervical cancer patients may require
      more opioids among those with gynecologic malignancies.

PMID- 24906850
TI  - Research into a functional cure for HIV in neonates: the need for ethical
      foresight.
AB  - In 2013, researchers announced that a newborn child from Mississippi, USA might
      have been functionally cured of HIV by being given combination antiretroviral
      therapy within hours of birth. Public and media attention has since been captured
      by the possibility of finding a cure for HIV transmitted from mother to child.
      Research into the strategy used for the Mississippi patient is crucially
      important to establish whether it can be replicated and shown to work in diverse
      populations. At the same time, any ethical issues likely to arise in such studies
      should be addressed and not ignored in the pursuit of a functional cure. In this
      Personal View we identify ethical issues that could arise in research towards
      achievment of a functional cure for HIV in neonates, including difficult trade
      offs associated with choosing the study population and questions about the
      broader social implications of the research, and propose ways to resolve them. 

PMID- 24906851
TI  - The potential impact of HPV-16 reactivation on prevalence in older Australians.
AB  - BACKGROUND: Some regional cross-sectional human papillomavirus (HPV) DNA
      prevalence data show an increase in prevalence in older women, the reasons for
      which are as yet unknown. A recently published study suggests that the increase
      may be at least partly due to reactivation of latent HPV in menopausal women.
      METHODS: We developed a dynamic mathematical model of HPV-16 transmission to
      estimate the key consequences of hypothetical HPV-16 reactivation in the
      Australian heterosexual population. We only consider a worst case scenario with
      regard to reactivation in the Australian setting when all women who are latently
      infected reactivate and, wherever feasible, we choose model parameter values
      which may lead to a more pronounced reactivation. The ongoing National HPV
      vaccination program covering both women and men is incorporated in the model.
      RESULTS: We estimate that about 1 in 10 women and men who appear to have cleared
      HPV-16 infection may be latently infected. The prevalence of HPV-16 in older
      Australian women will increase by a factor of up to 3.1 between now and 2025
      which will be accompanied by an increase by a factor of around 1.9 in older men.
      However, the long-term impact of the HPV vaccination is not significantly altered
      by reactivation. CONCLUSIONS: If the reactivation hypothesis we consider is
      substantiated, the public health response should be focused on further
      improvement of cervical screening coverage for older women. Our study also
      highlights the urgent need for surveillance of HPV prevalence in older
      Australians.

PMID- 24906852
TI  - Intratypic heterologous vaccination of calves can induce an antibody response in
      presence of maternal antibodies against foot-and-mouth disease virus.
AB  - BACKGROUND: Maternal antibodies can interfere with foot-and-mouth disease
      vaccination. In this study we determined whether intratypic heterologous
      vaccination could help to improve herd immunity. RESULTS: In unvaccinated calves,
      a half-life of maternal antibodies of 21 days was determined. At two weeks of
      age, calves without maternal antibodies showed a good antibody response against
      both vaccines used in the trial, while in calves with maternal antibodies no
      antibody response to homologous vaccination (A Turkey 14/98) but a limited
      antibody response to intratypic heterologous vaccination (A22 Iraq) was observed.
      CONCLUSION: Two weeks old calves without maternal antibodies respond well to
      vaccination, but when emergency vaccination is carried out in a region that uses
      prophylactic vaccination, using an intratypic heterologous vaccine strain may
      improve the immunity in calves with maternal antibodies.

PMID- 24906853
TI  - Activation of JNK1/2 and p38 MAPK signaling pathways promotes enterovirus 71
      infection in immature dendritic cells.
AB  - BACKGROUND: c-Jun NH2-terminal kinase/stress-activated kinase (JNK/SAPK) and the
      p38 mitogen-activated protein kinase (p38 MAPK) are important components of
      cellular signal transduction pathways, which have been reported to be involved in
      viral replication. However, little is known about JNK1/2 and p38 MAPK signaling
      pathways in enterovirus 71 (EV71)-infected immature dendritic cells (iDCs). Thus,
      iDCs were induced from peripheral blood mononuclear cells (PBMC) and performed to
      explore the expressions and phosphorylation of molecules in the two signaling
      pathways as well as secretions of inflammatory cytokines and interferons during
      EV71 replication. RESULTS: We showed that EV71 infection could activate both
      JNK1/2 and p38 MAPK in iDCs and phosphorylate their downstream transcription
      factors c-Fos and c-Jun, which further promoted the production of IL-2, IL-6, IL
      10, and TNF-alpha. Moreover, EV71 infection also increased the release of IFN
      beta and IL-12 p40. Pretreatment of iDCs with SP600125 and SB203580 (20 MUM)
      could severely impair viral replication and its induced phosphorylation of
      JNK1/2,p38 MAPK, c-Fos and c-Jun. In addition, treatment of EV71-infected iDCs
      with SP600125 and SB203580 could inhibit secretions of IL-6, IL-10 and TNF-alpha.
      CONCLUSION: JNK1/2 and p38 MAPK signaling pathways are beneficial to EV71
      infection and positively regulate secretions of inflammatory cytokines in iDCs.

PMID- 24906854
TI  - Plasma homocysteine concentrations in acute and convalescent changes of central
      retinal vein occlusion in a Chinese population.
AB  - PURPOSE: Homocysteine is a potential risk factor for central retinal vein
      occlusion (CRVO), but this remains controversial. We measured fasting total
      plasma homocysteine (tHcy) concentrations immediately after CRVO and in the
      convalescent period to investigate this controversy. METHODS: We measured fasting
      tHcy concentrations in 36 consecutive patients with CRVO within three days; and
      at 1, 3, and 6 months after CRVO; and once in 36 control subjects. The vitamin
      B12 and folate levels, and the presence of C677T MTHFR polymorphisms, were
      analyzed in all patients and controls. RESULTS: Median tHcy concentrations were
      not significantly higher than in matched control subjects in the acute phase of
      CRVO (9.66 [10.75 +/- 4.09] vs. 9.25 [9.96 +/- 4.02] MUmol/L, P = 0.371) and 1
      month after CRVO (P = 0.119). However, tHcy levels increased significantly in the
      convalescent period and were significantly higher than in control subjects at 3
      CRVO (P = 0.010) and 6 (P < 0.001) months after CRVO. Furthermore, tHcy levels of
      the ischemic CRVO patients at 6 months after CRVO were significantly higher than
      in nonischemic CRVO patients (P = 0.028). However, these observations did not
      appear to be explained by alteration in serum folate, vitamin B12 concentrations,
      and the MTHFR C677T genotype. CONCLUSIONS: The tHcy levels are not immediately
      elevated after CRVO, but increase in the convalescent period. These data do not
      support the hypothesis that raised tHcy concentrations are independent risk
      factor for CRVO. Instead, it is possible that elevated tHcy levels may be caused
      by the disease process itself.

PMID- 24906855
TI  - Generation of a biomimetic human artificial cornea model using Wharton's jelly
      mesenchymal stem cells.
AB  - PURPOSE: Human Wharton's jelly stem cells (HWJSCs) are able to differentiate into
      skin and oral mucosa epithelial-like cells. In this work, we demonstrate for the
      first time the capability of HWJSCs to differentiate in vitro into cornea
      epithelial-like cells in a three-dimensional model. METHODS: First, primary cell
      cultures of HWJSCs, corneal epithelial cells, and corneal keratocytes were
      cultured and three-dimensional orthotypic and heterotypic human cornea models
      were generated with fibrin-agarose scaffolds. Then, in vitro differentiation of
      HWJSCs and corneal epithelial cells was performed with keratinocytic inductive
      medium in a three-dimensional system that allowed interaction between stromal and
      epithelial compartments. Histological, histochemical, and immunofluorescence
      analyses were used to determine the differentiation status of each sample.
      RESULTS: Our results demonstrated that HWJSCs were able to differentiate into
      corneal epithelial-like cells, with results similar to the native cornea.
      Heterotypical corneas generated with HWJSCs showed adequate differentiation of
      the epithelium and stroma, and were similar to orthotypic and native corneas in
      the expression of epithelial markers (CK3/12, PKG, ZO1, and CX43) and
      extracellular matrix components (proteoglycans, collagen, elastic and reticular
      fibers). Immunofluorescence analysis confirmed the presence of crystallins Cry
      alphaA, Cry-alphaB, Cry-beta, and Cry-zeta with moderate or weak expression of
      Cry-betagamma3 and Cry-lambda1 (key proteins involved in cornea transparency) in
      both models. CONCLUSIONS: Our findings suggest that HWJSCs can be considered an
      alternative cell source for cornea regeneration and may offer a solution for
      patients with limbus stem cell deficiency.

PMID- 24906856
TI  - TGF-beta2-mediated ocular hypertension is attenuated in SPARC-null mice.
AB  - PURPOSE: Transforming growth factor-beta2 (TGF-beta2) has been implicated in the
      pathogenesis of primary open-angle glaucoma through extracellular matrix (ECM)
      alteration among various mechanisms. Secreted protein acidic and rich in cysteine
      (SPARC) is a matricellular protein that regulates ECM within the trabecular
      meshwork (TM), and is highly upregulated by TGF-beta2. We hypothesized that, in
      vivo, SPARC is a critical regulatory node in TGF-beta2-mediated ocular
      hypertension. METHODS: Empty (Ad.empty) or TGF-beta2-containing adenovirus
      (Ad.TGF-beta2) was injected intravitreally into C57BL6-SV129 WT and SPARC-null
      mice. An initial study was performed to identify a stable period for IOP
      measurement under isoflurane. The IOP was measured before injection and every
      other day for two weeks using rebound tonometry. Additional mice were euthanized
      at peak IOP for immunohistochemistry. RESULTS: The IOP was stable under
      isoflurane during minutes 5 to 8. The IOP was significantly elevated in Ad.TGF
      beta2-injected (n = 8) versus Ad.empty-injected WT (n = 8) mice and contralateral
      uninjected eyes during days 4 to 11 (P < 0.03). The IOPs were not significantly
      elevated in Ad.TGF-beta2-injected versus Ad.empty-injected SPARC-null mice.
      However, on day 8, the IOP of Ad.TGF-beta2-injected SPARC-null eyes was elevated
      compared to that of contralateral uninjected eyes (P = 0.0385).
      Immunohistochemistry demonstrated that TGF-beta2 stimulated increases in collagen
      IV, fibronectin, plasminogen activator inhibitor-1 (PAI-1), connective tissue
      growth factor (CTGF), and SPARC in WT mice, but only PAI-1 and CTGF in SPARC-null
      mice (P < 0.05). CONCLUSIONS: SPARC is essential to the regulation of TGF-beta2
      mediated ocular hypertension. Deletion of SPARC significantly attenuates the
      effects of TGF-beta2 by restricting collagen IV and fibronectin expression. These
      data provide further evidence that SPARC may have an important role in IOP
      regulation and possibly glaucoma pathogenesis.

PMID- 24906857
TI  - Effect of intravitreal triamcinolone acetonide or bevacizumab on choroidal
      thickness in eyes with diabetic macular edema.
AB  - PURPOSE: We evaluated the effect of intravitreal triamcinolone acetonide (IVTA)
      or intravitreal bevacizumab (IVB) on subfoveal choroidal thickness (SFCT) in eyes
      with diabetic macular edema (DME). METHODS: In this prospective, randomized,
      interventional comparative study, 51 DME eyes of 51 patients were randomized to
      receive either IVTA or IVB. The central macular thickness (CMT) and SFCT were
      determined by optical coherence tomography at 24 hours, 7 days, and 4, 8, and 12
      weeks. The SFCT at 1500 and 3000 MUm nasal or temporal to the central fovea also
      was measured. The values obtained before were compared to those obtained 12 weeks
      after the injections. RESULTS: The eyes were randomly assigned to the IVTA (25
      eyes) and IVB (26 eyes) groups. The SFCT was reduced significantly in the IVTA
      group from 24 hours to 12 weeks. The average +/- SD of the SFCT expressed as the
      ratio to baseline thickness decreased to 94.8% +/- 5.6% (P < 0.01) at 24 hours
      after IVTA and remained unchanged up to 12 weeks (91.8% +/- 10.5%, P < 0.01,
      Wilcoxon signed-rank test). In the IVB group, no significant difference was found
      in the SFCT after IVB for 12 weeks. The CMT decreased significantly in both
      groups from 24 hours to 4 weeks; however, the decrease was not significant at 8
      weeks or later in the IVB group. CONCLUSIONS: The decrease in choroidal thickness
      in eyes with DME after IVTA suggests that the choroidal pathology in diabetic
      retinopathy might be due to steroid-sensitive factors rather than vascular
      endothelial growth factor. (www.umin.ac.jp/ctr number, clinical trials number
      UMIN000009854.).

PMID- 24906858
TI  - Rare complement factor H variant associated with age-related macular degeneration
      in the Amish.
AB  - PURPOSE: Age-related macular degeneration is the leading cause of blindness among
      the adult population in the developed world. To further the understanding of this
      disease, we have studied the genetically isolated Amish population of Ohio and
      Indiana. METHODS: Cumulative genetic risk scores were calculated using the 19
      known allelic associations. Exome sequencing was performed in three members of a
      small Amish family with AMD who lacked the common risk alleles in complement
      factor H (CFH) and ARMS2/HTRA1. Follow-up genotyping and association analysis was
      performed in a cohort of 973 Amish individuals, including 95 with self-reported
      AMD. RESULTS: The cumulative genetic risk score analysis generated a mean genetic
      risk score of 1.12 (95% confidence interval [CI]: 1.10, 1.13) in the Amish
      controls and 1.18 (95% CI: 1.13, 1.22) in the Amish cases. This mean difference
      in genetic risk scores is statistically significant (P = 0.0042). Exome
      sequencing identified a rare variant (P503A) in CFH. Association analysis in the
      remainder of the Amish sample revealed that the P503A variant is significantly
      associated with AMD (P = 9.27 * 10(-13)). Variant P503A was absent when evaluated
      in a cohort of 791 elderly non-Amish controls, and 1456 non-Amish cases.
      CONCLUSIONS: Data from the cumulative genetic risk score analysis suggests that
      the variants reported by the AMDGene consortium account for a smaller genetic
      burden of disease in the Amish compared with the non-Amish Caucasian population.
      Using exome sequencing data, we identified a novel missense mutation that is
      shared among a densely affected nuclear Amish family and located in a gene that
      has been previously implicated in AMD risk.

PMID- 24906859
TI  - In vivo imaging of human cone photoreceptor inner segments.
AB  - PURPOSE: An often overlooked prerequisite to cone photoreceptor gene therapy
      development is residual photoreceptor structure that can be rescued. While
      advances in adaptive optics (AO) retinal imaging have recently enabled direct
      visualization of individual cone and rod photoreceptors in the living human
      retina, these techniques largely detect strongly directionally-backscattered
      (waveguided) light from normal intact photoreceptors. This represents a major
      limitation in using existing AO imaging to quantify structure of remnant cones in
      degenerating retina. METHODS: Photoreceptor inner segment structure was assessed
      with a novel AO scanning light ophthalmoscopy (AOSLO) differential phase
      technique, that we termed nonconfocal split-detector, in two healthy subjects and
      four subjects with achromatopsia. Ex vivo preparations of five healthy donor eyes
      were analyzed for comparison of inner segment diameter to that measured in vivo
      with split-detector AOSLO. RESULTS: Nonconfocal split-detector AOSLO reveals the
      photoreceptor inner segment with or without the presence of a waveguiding outer
      segment. The diameter of inner segments measured in vivo is in good agreement
      with histology. A substantial number of foveal and parafoveal cone photoreceptors
      with apparently intact inner segments were identified in patients with the
      inherited disease achromatopsia. CONCLUSIONS: The application of nonconfocal
      split-detector to emerging human gene therapy trials will improve the potential
      of therapeutic success, by identifying patients with sufficient retained
      photoreceptor structure to benefit the most from intervention. Additionally,
      split-detector imaging may be useful for studies of other retinal degenerations
      such as AMD, retinitis pigmentosa, and choroideremia where the outer segment is
      lost before the remainder of the photoreceptor cell.

PMID- 24906860
TI  - Regulation of intrinsic axon growth ability at retinal ganglion cell growth
      cones.
AB  - PURPOSE: Mammalian central nervous system neurons fail to regenerate after injury
      or disease, in part due to a progressive loss in intrinsic axon growth ability
      after birth. Whether lost axon growth ability is due to limited growth resources
      or to changes in the axonal growth cone is unknown. METHODS: Static and time
      lapse images of purified retinal ganglion cells (RGCs) were analyzed for axon
      growth rate and growth cone morphology and dynamics without treatment and after
      manipulating Kruppel-like transcription factor (KLF) expression or applying
      mechanical tension. RESULTS: Retinal ganglion cells undergo a developmental
      switch in growth cone dynamics that mirrors the decline in postnatal axon growth
      rates, with increased filopodial adhesion and decreased lamellar protrusion area
      in postnatal axonal growth cones. Moreover, expressing growth-suppressive KLF4 or
      growth-enhancing KLF6 transcription factors elicits similar changes in postnatal
      growth cones that correlate with axon growth rates. Postnatal RGC axon growth
      rate is not limited by an inability to achieve axon growth rates similar to
      embryonic RGCs; indeed, postnatal axons support elongation rates up to 100-fold
      faster than postnatal axonal growth rates. Rather, the intrinsic capacity for
      rapid axon growth is due to both growth cone pausing and retraction, as well as
      to a slightly decreased ability to achieve rapid instantaneous rates of forward
      progression. Finally, we observed that RGC axon and dendrite growth are regulated
      independently in vitro. CONCLUSIONS: Together, these data support the hypothesis
      that intrinsic axon growth rate is regulated by an axon-specific growth program
      that differentially regulates growth cone motility.

PMID- 24906861
TI  - Decrease of murine cytomegalovirus-induced retinitis by intravenous delivery of
      immediate early protein-3-specific siRNA.
AB  - PURPOSE: Retinitis induced by both human and murine cytomegaloviruses following
      immunosuppression is characterized by progressive loss of retinal architecture,
      due to necrosis of virus-infected cells as well as widespread apoptosis of
      uninfected bystander cells. Because small inhibitory RNA molecules (siRNA) can
      reduce murine cytomegalovirus (MCMV) gene expression and thereby inhibit virus
      replication in vitro, we tested siRNAs directed against MCMV immediate early
      protein-3 (IE-3) to determine if MCMV-induced retinitis could be alleviated in
      vivo. METHODS: Immunosuppressed Balb/c mice (2.0 mg methylprednisolone acetate
      every 3 days beginning on day -2) were infected with 5 * 10(3) pfu of the K181
      strain of MCMV via the supraciliary route. At day 2 post infection, mice were
      treated with various doses of IE-3-specific siRNA ranging from 0.1 nmol to 10
      nmol, in a volume of 20 MUL PBS via tail vein injection. Injected eyes were
      collected at various times post inoculation and subjected to plaque assay for
      virus titer, MCMV antigen staining, H&E staining, TUNEL assay, and Western blot
      for MCMV IE-3 protein. RESULTS: Small but significant amounts of fluorescently
      labeled IE-3-specific siRNA localized to the RPE layer 48 hours after intravenous
      injection. IE-3-specific siRNA significantly reduced virus titers at all
      concentrations tested (ranging from 0.1 nmol to 10 nmol), but the most potent
      effect of siRNA was observed at a dose of 1 nmol. We also observed that IE-3
      specific siRNA produced a substantial decrease in MCMV titers and a substantial
      reduction in bystander cell apoptosis over the time course of virus infection.
      CONCLUSIONS: Systemic administration of IE-3-specific siRNA could alleviate MCMV
      retinitis by inhibiting virus replication and subsequent death of uninfected
      retinal cells.

PMID- 24906862
TI  - Geospatial distribution and clustering of Chlamydia trachomatis in communities
      undergoing mass azithromycin treatment.
AB  - PURPOSE: We detected spatial clustering of households with Chlamydia trachomatis
      infection (CI) and active trachoma (AT) in villages undergoing mass treatment
      with azithromycin (MDA) over time. METHODS: We obtained global positioning system
      (GPS) coordinates for all households in four villages in Kongwa District,
      Tanzania. Every 6 months for a period of 42 months, our team examined all
      children under 10 for AT, and tested for CI with ocular swabbing and Amplicor.
      Villages underwent four rounds of annual MDA. We classified households as having
      >=1 child with CI (or AT) or having 0 children with CI (or AT). We calculated the
      difference in the K function between households with and without CI or AT to
      detect clustering at each time point. RESULTS: Between 918 and 991 households
      were included over the 42 months of this analysis. At baseline, 306 households
      (32.59%) had >=1 child with CI, which declined to 73 households (7.50%) at 42
      months. We observed borderline clustering of households with CI at 12 months
      after one round of MDA and statistically significant clustering with growing
      cluster sizes between 18 and 24 months after two rounds of MDA. Clusters
      diminished in size at 30 months after 3 rounds of MDA. Active trachoma did not
      cluster at any time point. CONCLUSIONS: This study demonstrates that CI clusters
      after multiple rounds of MDA. Clusters of infection may increase in size if the
      annual antibiotic pressure is removed. The absence of growth after the three
      rounds suggests the start of control of transmission.

PMID- 24906863
TI  - Estimating minimally important differences for two vision-specific quality of
      life measures.
AB  - PURPOSE: To estimate minimally important differences (MIDs) for the Visual
      Activities Questionnaire (VAQ) and the National Eye Institute-Visual Function
      Questionnaire (NEI-VFQ). METHODS: A total of 607 subjects with newly-diagnosed
      open-angle glaucoma (OAG) was enrolled in the Collaborative Initial Glaucoma
      Treatment Study (CIGTS) and randomized to initial treatment with medications or
      surgery. Subjects underwent an ophthalmic examination and telephone-administered
      quality of life (QOL) interview before randomization and every six months
      thereafter. The VAQ and NEI-VFQ were used to assess participants' perceptions of
      their visual function. Clinical measures included the mean deviation (MD) from
      Humphrey 24-2 full threshold visual field (VF) testing, and best-corrected visual
      acuity (VA) measured using the Early Treatment Diabetic Retinopathy Study (ETDRS)
      protocol. Anchor-based (using MD and VA) and distribution-based methods were used
      to estimate MIDs. RESULTS: Anchor-based cross-sectional analyses at 66 months
      follow-up found a 10-letter increment in better eye VA corresponded to MIDs of
      5.2 units for VAQ and 3.8 units for NEI-VFQ total scores. A 3-dB increment in the
      better eye MD yielded MIDs of 2.6 and 2.3 units for the same two questionnaires.
      In longitudinal analyses, MIDs for the VAQ were 3.2 units for a 10-letter change
      of VA and 3.4 units for a 3-dB change in the MD. Distribution-based MIDs were
      larger. CONCLUSIONS: A range of MIDs for the VAQ (2.6-6.5 units) and NEI-VFQ (2.3
      3.8 units) was found. Although similar in magnitude, MIDs were sensitive to the
      MID estimation method, the anchor chosen, and differences between questionnaires.
      (ClinicalTrials.gov number, NCT00000149.).

PMID- 24906864
TI  - Ozone levels in European and USA cities are increasing more than at rural sites,
      while peak values are decreasing.
AB  - Ground-level ozone (O3) levels are usually lower in urban centers than nearby
      rural sites. To compare trends in O3 levels during the period 1990-2010, we
      obtained monitoring data from paired urban and rural sites from the European
      Environment Agency and the US Environmental Protection Agency. Ozone peaks
      decreased at both station types, with no significant differences between urban
      and rural stations. Ozone annual averages increased at both urban and rural
      sites, with a faster rate of increase for urban centers. The overall trend was
      for convergence between urban and rural O3 data. Ozone levels exceeded the
      criteria established for the protection of human and vegetation health at both
      urban and rural sites. 

PMID- 24906865
TI  - Post-external dacryocystorhinostomy lagophthalmos.
AB  - To describe lagophthalmos and eyelid closure abnormality after external
      dacryocystorhinostomy (DCR). A retrospective review of medical records and
      postoperative photographs of 79 patients who underwent external DCR for
      nasolacrimal duct obstruction and developed eyelid closure abnormality and
      lagophthalmos with or without exposure keratopathy was conducted. Collected data
      included age, sex, indication for surgery, laterality, length and type of
      incision, length of follow-up duration, presence of punctate epithelial
      keratopathy, and time for resolution of eyelid closure abnormalities. Twenty
      seven patients with 28 external dacryocystorhinostomy had postoperative eyelid
      closure abnormalities. Male to female ratio was 1:6. The mean age was 40.1 years
      (range 9-80 years). All surgeries were performed through diagonal skin incision.
      Lagophthalmos involving the medial third of the palpebral fissure was noticed in
      28.6 % of cases. All patients had hypometric blink mainly of the upper eyelid.
      One patient had punctate epithelial keratopathy. Resolution of lagophthalmos was
      noticed over a period of 1-5 weeks with an average of 3 weeks. None of the
      patients continued to have residual hypometric blink or punctate keratopathy at
      the last follow-up time. The mean follow-up period was 4.2 months (range 3-6
      months). Eyelid closure abnormality and lagophthalmos after external DCR are
      underestimated problems. Spontaneous resolution is seen in all cases weeks to
      months after surgery.

PMID- 24906866
TI  - The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells
      toward enhanced anti-tumor immunity.
AB  - In addition to direct tumor cell cytotoxicity, chemotherapy can mediate tumor
      reduction through immune modulation of the tumor microenvironment to promote anti
      tumor immunity. Mature dendritic cells (DCs) play key roles in priming robust
      immune responses in tumor-bearing hosts. Here, we screened a panel of 21
      anticancer agents with defined molecular targets for their ability to induce
      direct maturation of DCs. We identified ansamitocin P3, a microtubule
      depolymerizing agent, as a potent inducer of phenotypic and functional maturation
      of DCs. Exposure of both murine spleen-derived and human monocyte-derived DCs to
      ansamitocin P3 triggered up-regulation of maturation markers and production of
      pro-inflammatory cytokines, resulting in an enhanced T cell stimulatory capacity.
      Local administration of ansamitocin P3 induced maturation of skin Langerhans
      cells in vivo and promoted antigen uptake and extensive homing of tumor-resident
      DCs to tumor-draining lymph nodes. When used as an adjuvant in a specific
      vaccination approach, ansamitocin P3 dramatically increased activation of antigen
      specific T cells. Finally, we demonstrate that ansamitocin P3, due to its
      immunomodulatory properties, acts in synergy with antibody-mediated blockade of
      the T cell inhibitory receptors PD-1 and CTLA-4. The combination treatment was
      most effective and induced durable growth inhibition of established tumors.
      Mechanistically, we observed a reduced regulatory T cell frequency and improved T
      cell effector function at the tumor site. Taken together, our study unravels an
      immune-based anti-tumor mechanism exploited by microtubule-depolymerizing agents,
      including ansamitocin P3, and paves the way for future clinical trials combining
      this class of agents with immunotherapy. 

PMID- 24906867
TI  - Reclaiming the spent alkaline zinc manganese dioxide batteries collected from the
      manufacturers to prepare valuable electrolytic zinc and LiNi0.5Mn1.5O4 materials.
AB  - A process for reclaiming the materials in spent alkaline zinc manganese dioxide
      (Zn-Mn) batteries collected from the manufacturers to prepare valuable
      electrolytic zinc and LiNi0.5Mn1.5O4 materials is presented. After dismantling
      battery cans, the iron cans, covers, electric rods, organic separator, label,
      sealing materials, and electrolyte are separated through the washing, magnetic
      separation, filtrating, and sieving operations. Then, the powder residues react
      with H2SO4 (2 mol L(-1)) solution to dissolve zinc under a liquid/solid ratio of
      3:1 at room temperature, and subsequently, the electrolytic Zn with purity of
      ?99.8% is recovered in an electrolytic cell with a cathode efficiency of ?85%
      under the conditions of 37-40 degrees C and 300 A m(-2). The most of MnO2 and a
      small quantity of electrolytic MnO2 are recovered from the filtration residue and
      the electrodeposit on the anode of electrolytic cell, respectively. The recovered
      manganese oxides are used to synthesize LiNi0.5Mn1.5O4 material of lithium-ion
      battery. The as-synthesized LiNi0.5Mn1.5O4 discharges 118.3 mAh g(-1) capacity
      and 4.7 V voltage plateau, which is comparable to the sample synthesized using
      commercial electrolytic MnO2. This process can recover the substances in the
      spent Zn-Mn batteries and innocuously treat the wastewaters, indicating that it
      is environmentally acceptable and applicable.

PMID- 24906868
TI  - Surveillance of dialysis events: 12-month experience at five outpatient adult
      hemodialysis centers in Kuwait.
AB  - BACKGROUND: Embedding dialysis surveillance scheme is associated with reductions
      in blood stream infection and antimicrobial consumption .The aim of this study
      was to establish baseline dialysis events (DE) rates; hospitalization,
      intravenous (IV) antibiotics start or a positive blood culture stratified by
      vascular access category and comparisons to published National Healthcare Safety
      Network (NHSN) rates. METHODS: A retrospective review of DE was done between
      January to December 2012, in five outpatient adult hemodialysis center. RESULTS:
      The pooled mean rates of hospitalization among patients with fistulas, grafts,
      permanent and temporary catheters were 2.8, 5.7, 5.1, and 10.6 per 100 patient
      months, respectively. For positive blood culture the pooled mean rates were 0.2,
      1.0, 1.9 and 2.7 per 100 patient-months in these groups. The IV antibiotics
      starts event pooled mean rates were 5.9, 9.0, 11.8, and 11.2 per 100 patient
      months. DE were significantly more common in patients with permanent and
      temporary catheters when compared with patients with fistulas and graft
      (p<0.001). CONCLUSION: Surveillance of DE rates in Kuwait revealed significantly
      lower mean rate of hospitalization and positive blood culture while IV
      antimicrobial start shows significantly higher mean rate when compared to
      published NHSN data.

PMID- 24906869
TI  - Morphological and electrophysiological outcome in prospective intravitreal
      bevacizumab treatment of macular edema secondary to central retinal vein
      occlusion.
AB  - PURPOSE: To evaluate intravitreal bevacizumab (IVB) treatment in patients with
      central retinal vein occlusion (CRVO) by spectral domain optical coherence
      tomography (OCT) and electroretinography (ERG). METHODS: Twenty-two CRVO patients
      were treated with IVB injections and followed for 1 year. Morphological effect of
      treatment was observed with fluorescent angiography and OCT. Functional effect
      was followed with best corrected visual acuity (BCVA) and ERG: combined rod-cone
      response of the standard full-field ERG (dark adapted 3.0 ERG), photopic negative
      response (PhNR), and pattern ERG (PERG). RESULTS: Best corrected visual acuity
      (BCVA) improved by 18.2 letters after 6 months (p <= 0.001) and additional 4.7
      letters by the 12th month (p <= 0.001). The central retinal thickness of 829.8 +/
      256.7 MUm decreased to 398.8 +/- 230 MUm (p <= 0.001) after 6 months and to
      303.7 +/- 128.9 MUm during the following 6 months (p <= 0.001). The total macular
      volume (14.4 +/- 4.2 mm(3)) decreased to 9.6 +/- 3.2 mm(3) and 8.5 +/- 2.0 mm(3)
      after 6 months and 1 year of treatment, respectively (p <= 0.001).
      Electrophysiological measures improved significantly after 6 months and 1 year of
      treatment: the a-wave implicit time of dark adapted 3.0 ERG from 25.6 +/- 2.3 to
      24.1 +/- 2.1 and 24.1 +/- 2.0 ms (p <= 0.01); the PhNR from -5.9 +/- 6.6 to -9.4
      +/- 6.1 and -10.4 +/- 4.6 uV (p <= 0.05); the PERG P50 amplitude from 0.2 +/- 0.3
      to 0.9 +/- 0.6 and 1.1 +/- 0.6 uV (p <= 0.001); and N95 amplitude from 0.4 +/-
      0.6 to 1.2 +/- 0.9 and 1.6 +/- 0.9 uV (p <= 0.001). CONCLUSIONS: Intravitreal
      bevacizumab (IVB) treatment of macular edema due to CRVO improved standard
      morphological measures and the electrophysiological function of outer and inner
      retinal layers, which was most evident in central retina.

PMID- 24906870
TI  - De novo expression of sodium-glucose cotransporter SGLT2 in Bowman's capsule
      coincides with replacement of parietal epithelial cell layer with proximal tubule
      like epithelium.
AB  - In kidney nephron, parietal epithelial cells line the Bowman's capsule and
      function as a permeability barrier for the glomerular filtrate. Bowman's capsule
      cells with proximal tubule epithelial morphology have been found. However, the
      effects of tubular metaplasia in Bowman's capsule on kidney function remain
      poorly understood. Sodium-glucose cotransporter 2 (SGLT2) plays a major role in
      reabsorption of glucose in the kidney and is expressed on brush border membrane
      (BBM) of epithelial cells in the early segment of the proximal tubule. We
      hypothesized that SGLT2 is expressed in tubularized Bowman's capsule and used our
      novel antibody to test this hypothesis. Immunohistochemical analysis was
      performed with our SGLT2 antibody on C57BL/6 mouse kidney prone to have
      tubularized Bowman's capsules. Cell membrane was examined with periodic acid
      Schiff (PAS) stain. The results showed that SGLT2 was localized on BBM of the
      proximal tubules in young and adult mice. Bowman's capsules were lined mostly
      with normal brush border-less parietal epithelial cells in young mice, while they
      were almost completely covered with proximal tubule-like cells in adult mice.
      Regardless of age, SGLT2 was expressed on BBM of the tubularized Bowman's capsule
      but did not co-localize with nephrin in the glomerulus. SGLT2-expressing tubular
      cells expanded from the urinary pole toward the vascular pole of the Bowman's
      capsule. This study identified the localization of SGLT2 in the Bowman's capsule.
      Bowman's capsules with tubular metaplasia may acquire roles in reabsorption of
      filtered glucose and sodium. 

PMID- 24906871
TI  - Can Porcine circovirus type 2 (PCV2) infection be eradicated by mass vaccination?
AB  - The feasibility to eradicate Porcine circovirus type 2 (PCV2) in a conventional
      PCV2 infected farm by vaccinating both sows and piglets using a commercially
      subunit vaccine was assessed. Vaccination strategy implied that all sows, boars
      and gilts of the farm were vaccinated every four months, and all piglets
      vaccinated and revaccinated with the same vaccine at 4 and 7 weeks of age,
      respectively. This vaccination strategy was applied during 12 consecutive months.
      Blood samples from 15 piglets of 4, 8, 12, 16, 20 and 24 weeks of age and 15 sows
      were taken monthly PRE, DURING and POST mass vaccination strategy. From all the
      collected sera (n=1796), a representative proportion of them (n=1235, 69%) were
      analysed (n=1121 from piglets and n=114 from sows). All these samples were tested
      by PCV2 ELISA and PCV2 PCR (and quantitative-PCR when PCR positive). All tested
      sows were negative by PCR but seropositive. ELISA mean OD values of sows
      decreased throughout the study. Percentages of PCV2 PCR positive samples in
      piglets were 8% (12/150), 0.9% (6/659) and 3.5% (11/312) PRE, DURING and POST
      application of the mass vaccination program, respectively. ELISA mean OD values
      of PCV2 seropositive animals progressively decreased until the end of the mass
      vaccination period, but a clear seroconversion was observed after stopping such
      strategy. In conclusion, one year period of mass PCV2 vaccination (without
      implementing further farm management practices or biosafety measures) was not
      able to clear out PCV2 infection, and the virus became detectable again when
      vaccination was stopped. 

PMID- 24906872
TI  - Virion-associated viral proteins of a Chinese giant salamander (Andrias
      davidianus) iridovirus (genus Ranavirus) and functional study of the major capsid
      protein (MCP).
AB  - Chinese giant salamander iridovirus (CGSIV) is the emerging causative agent to
      farmed Chinese giant salamanders in nationwide China. CGSIV is a member of the
      common midwife toad ranavirus (CMTV) subset of the amphibian-like ranavirus
      (ALRV) in the genus Ranavirus of Iridoviridae family. However, viral protein
      information on ALRV is lacking. In this first proteomic analysis of ALRV, 40
      CGSIV viral proteins were detected from purified virus particles by liquid
      chromatography-tandem mass spectrometry analysis. The transcription products of
      all 40 identified virion proteins were confirmed by reverse transcription
      polymerase chain reaction analysis. Temporal expression pattern analysis combined
      with drug inhibition assay indicated that 37 transcripts of the 40 virion protein
      genes could be classified into three temporal kinetic classes, namely, 5
      immediate early, 12 delayed early, and 20 late genes. The presence of major
      capsid proteins (MCP, ORF019L) and a proliferating cell nuclear antigen (ORF025L)
      was further confirmed by Western blot analysis. The functions of MCP were also
      determined by small interfering RNA (siRNA)-based knockdown assay and anti
      recombinant MCP serum-based neutralization testing. At low dosages of CGSIV,
      siRNA-based knockdown of the MCP gene effectively inhibited CGSIV replication in
      fathead minnow cells. The antiviral effect observed in the anti-MCP serum-based
      neutralization test confirms the crucial function of the MCP gene in CGSIV
      replication. Taken together, detailed information on the virion-associated viral
      proteins of ALRV is presented for the first time. Our results also provide
      evidence that MCP is essential for CGSIV replication in vitro. 

PMID- 24906873
TI  - Macular dystrophy associated with the mitochondrial DNA A3243G mutation:
      pericentral pigment deposits or atrophy? Report of two cases and review of the
      literature.
AB  - BACKGROUND: The A3243G point mutation in mitochondrial DNA (mtDNA) is associated
      with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like
      episodes) and MIDD syndromes (maternally inherited diabetes and deafness). Both
      MELAS and MIDD patients can present with visual symptoms due to a retinopathy,
      sometimes before the genetic diagnosis is made. CASE PRESENTATION: Patient 1: 46
      year-old woman with diabetes mellitus and hearing loss was referred for an
      unspecified maculopathy detected during screening evaluation for diabetic
      retinopathy. Visual acuity was 20/20 in both eyes. Fundus examination showed
      bilateral macular and peripapillary hyperpigmented/depigmented areas.Patient 2:
      45 year-old woman was referred for recent vision loss in her left eye. History
      was remarkable for chronic fatigue, migraine and diffuse muscular pain. Visual
      acuity was 20/20 in her right eye and 20/30 in her left eye. Fundus exhibited
      several nummular perifoveal islands of retinal pigment epithelium atrophy and
      adjacent pale deposits in both eyes.Retinal anatomy was investigated with
      autofluorescence, retinal angiography and optical coherence tomography. Retinal
      function was assessed with automated static perimetry, full-field and multifocal
      electroretinography and electro-oculography. Genetic testing of mtDNA identified
      a point mutation at the locus 3243. CONCLUSION: Observation of RPE abnormalities
      in the context of suggestive systemic findings should prompt mtDNA testing.

PMID- 24906875
TI  - [Current evidence for laparoscopic surgery of colonic cancer].
AB  - BACKGROUND: The development of modern videoendoscopy enables surgeons to perform
      laparoscopic resection of colonic cancer. AIM: This manuscript evaluated the
      literature concerning clinically relevant differences in the short and long-term
      course after laparoscopic or conventional resection of colonic cancer. METHODS:
      An investigation of meta-analyses from randomized controlled clinical trials
      comparing laparoscopic and conventional surgery for colonic cancer was carried
      out. RESULTS: The incidence of intraoperative complications was higher during
      laparoscopic surgery, the duration of surgery was increased and blood loss was
      less when compared to open surgery. Overall morbidity and the incidence of
      surgical complications were decreased after laparoscopic surgery. General
      morbidity and mortality were not different after laparoscopic or open resection
      of colonic cancer. Duration of hospital stay was shorter but was also associated
      with the type of perioperative care (i.e. traditional or enhanced recovery).
      Following minimally invasive or conventional resection, the incidence of tumor
      recurrence (local and distant) and the duration of survival (overall and disease
      free) showed no differences. Wound implantations were rare after both operative
      techniques but with a tendency to occur more often after laparoscopic than open
      resection. CONCLUSION: Laparoscopic resection of colonic cancer has clinically
      relevant short-term benefits for the patients and long-term results are not
      different from open colectomy. However, most of the patients included in
      randomized controlled trials underwent right or left colectomy and sigmoid or
      rectosigmoid resections. Data with a high level of evidence concerning carcinomas
      of the flexures or the transverse colon do not exist. Suitable patients with
      colonic cancer should undergo laparoscopic resection by experienced surgeons.

PMID- 24906874
TI  - Fine-mapping QTLs in advanced intercross lines and other outbred populations.
AB  - Quantitative genetic studies in model organisms, particularly in mice, have been
      extremely successful in identifying chromosomal regions that are associated with
      a wide variety of behavioral and other traits. However, it is now widely
      understood that identification of the underlying genes will be far more
      challenging. In the last few years, a variety of populations have been utilized
      in an effort to more finely map these chromosomal regions with the goal of
      identifying specific genes. The common property of these newer populations is
      that linkage disequilibrium spans relatively short distances, which permits fine
      scale mapping resolution. This review focuses on advanced intercross lines (AILs)
      which are the simplest such population. As originally proposed in 1995 by Darvasi
      and Soller, an AIL is the product of intercrossing two inbred strains beyond the
      F2 generation. Unlike recombinant inbred strains, AILs are maintained as outbred
      populations; brother-sister matings are specifically avoided. Each generation of
      intercrossing beyond the F2 further degrades linkage disequilibrium between
      adjacent makers, which allows for fine-scale mapping of quantitative trait loci
      (QTLs). Advances in genotyping technology and techniques for the statistical
      analysis of AILs have permitted rapid advances in the application of AILs. We
      review some of the analytical issues and available software, including QTLRel,
      EMMA, EMMAX, GEMMA, TASSEL, GRAMMAR, WOMBAT, Mendel, and others. 

PMID- 24906876
TI  - Neoadjuvant therapy combined with a BMP regimen for treating penile cancer
      patients with lymph node metastasis: a retrospective study in China.
AB  - BACKGROUND AND AIM: Combination chemotherapy is emerging in the management of
      advanced penile cancer. However, evidence-based chemotherapeutic regimens in the
      current guidelines are lacking. The aim of this study was to evaluate the
      efficacy of preoperative neoadjuvant chemotherapy combined with a BMP regimen
      including bleomycin (BLM), methopterin (MTX) and cisplatin (DDP) for treating
      advanced penile cancer patients. METHODS: We retrospectively audited the clinical
      and follow-up data of 24 penile cancer patients with fixed inguinal lymph node
      metastasis that were admitted in our hospital from 2001 to 2010 and received
      preoperative neoadjuvant chemotherapy. RESULTS: A total of 24 patients with
      advanced penile cancer (pN3) were recruited in this study. All patients received
      preoperative neoadjuvant chemotherapy combined with a BMP regimen. The average
      cycle of chemotherapy was two cycles (range 1-4 cycles). Among 24 adjuvant cases,
      15 patients that responded to neoadjuvant chemotherapy underwent penectomy and
      inguinal lymphadenectomy. In contrast, nine cases did not respond to chemotherapy
      and received palliative local radiotherapy. Overall, the 1-, 2- and 5-year
      survival rates were 70.8, 50.0 and 45.8 %, respectively. The 5-year survival rate
      between the responder and non-responder groups was statistically significant
      (73.3 vs. 0 %, P < 0.001). CONCLUSION: Neoadjuvant chemotherapy combined with a
      BMP regimen followed by surgery is beneficial to patients with advanced penile
      cancer.

PMID- 24906877
TI  - Prognostic impact of angiopoietin-2 in multiple myeloma.
AB  - PURPOSE: Angiogenesis is an essential process for the expansion of multiple
      myeloma (MM). Angiopoietin-2 (Ang-2), Ang-1 and their receptor possess important
      roles in this procedure. The aim of the study was to measure serum levels of Ang
      2 along with known markers of angiogenesis and to estimate their prognostic
      impact on the survival. METHODS: Bone marrow microvascular density (MVD),
      estimated by CD31, and circulating levels of known angiogenic factors Ang-2,
      interleukin-6, soluble CD105 and platelet-derived growth factor-AB, measured by
      ELISA, were measured in 77 newly diagnosed patients with active MM and in 57 of
      them who responded to chemotherapy. RESULTS: All measured parameters were
      increased in MM patients, were also increasing in advanced disease and decreased
      after effective treatment. Ang-2 correlated positively with the other angiogenic
      factors and MVD. Moreover, Ang-2 values above the median were accompanied by
      worse survival. CONCLUSION: Ang-2 correlates strongly with the angiogenic process
      and its serum levels are importantly prognostic for survival, highlighting the
      role of angiopoietins pathway in the biology of MM.

PMID- 24906878
TI  - Stereotactic body radiotherapy with flattening filter-free beams for prostate
      cancer: assessment of patient-reported quality of life.
AB  - PURPOSE: Stereotactic body radiotherapy (SBRT) is an emerging treatment approach
      reported as safe and effective strategy for low- and intermediate-risk prostate
      cancer patients. End point of the current study is to appraise the patient
      reported quality of life according to the expanded prostate cancer index
      composite (EPIC) questionnaire. METHODS: In the framework of a prospective mono
      institutional phase II trial, EPIC questionnaire was dispensed (up to 1 year
      after treatment) to a cohort of 46 patients of 72 treated with 5 fractions of 7
      Gy each to the prostate. SBRT was delivered with RapidArc VMAT with 10 MV
      flattening filter-free photon beams. RESULTS: Median follow-up of patients was
      14.5 months (range: 6-23). Acute rectal toxicity was mild (only 23/72 cases with
      G1-2 and no G3-4) as well as urinary (50/72 G1-2 and no G3-4). At the moment,
      four cases of G1 late rectal toxicity and 22 cases of G1 urinary (1 of G2) were
      reported. Urinary, rectal, sexual, and hormonal scores resulted stable over time:
      1 year scores resulted, respectively, in -0.3, +2.8, -1.7, and -2.8 % variations
      with respect to baseline. No significant differences were observed also when data
      were stratified according to functional and bother sub-scales. CONCLUSIONS:
      Stereotactic body radiotherapy (SBRT) treatment of prostate with RapidArc and
      high-intensity photon beams resulted to be well tolerated by patients with mild
      toxicity profiles and good patient-reported quality of life perception for the
      first year after treatment. Longer follow-up in the trial cohort is in progress.

PMID- 24906879
TI  - Acute kidney injury associated with Plasmodium malariae infection.
AB  - According to current estimates, Plasmodium malariae is not very common in
      Senegal, as more than 98% of malaria cases are suspected to be due to Plasmodium
      falciparum. However, it is possible that other malarial species are being under
      reported or misdiagnosed. This is a report of a case of P. malariae in a 30-year
      old man previously hospitalized with acute kidney injury after treatment with
      quinine and re-hospitalized three months later. He was diagnosed with renal
      cortical necrosis post malaria treatment. Plasmodium malariae was identified with
      light microscope and confirmed using species-specific small-subunit rRNA (ssrRNA)
      amplification.The patient was treated for malaria with intravenous quinine for
      seven days, followed by three days of oral treatment; the bacterial infection was
      treated using ceftriaxone during the first hospitalization and ciprofloxacin
      associated with ceftriaxone the second time. He also had four rounds of dialysis
      after which he partially recovered the renal function. Given the complications
      that can be caused by P. malariae infection, it should be systematically looked
      for, even if the predominant species is P. falciparum in Senegal. 

PMID- 24906880
TI  - PARG is dispensable for recovery from transient replicative stress but required
      to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged
      replicative stress.
AB  - Poly(ADP-ribosyl)ation is involved in numerous bio-logical processes including
      DNA repair, transcription and cell death. Cellular levels of poly(ADP-ribose)
      (PAR) are regulated by PAR polymerases (PARPs) and the degrading enzyme PAR
      glycohydrolase (PARG), controlling the cell fate decision between life and death
      in response to DNA damage. Replication stress is a source of DNA damage, leading
      to transient stalling of replication forks or to their collapse followed by the
      generation of double-strand breaks (DSB). The involvement of PARP-1 in
      replicative stress response has been described, whereas the consequences of a
      deregulated PAR catabolism are not yet well established. Here, we show that PARG
      deprived cells showed an enhanced sensitivity to the replication inhibitor
      hydroxyurea. PARG is dispensable to recover from transient replicative stress but
      is necessary to avoid massive PAR production upon prolonged replicative stress,
      conditions leading to fork collapse and DSB. Extensive PAR accumulation impairs
      replication protein A association with collapsed forks resulting in compromised
      DSB repair via homologous recombination. Our results highlight the critical role
      of PARG in tightly controlling PAR levels produced upon genotoxic stress to
      prevent the detrimental effects of PAR over-accumulation. 

PMID- 24906881
TI  - Dynamic condensation of linker histone C-terminal domain regulates chromatin
      structure.
AB  - The basic and intrinsically disordered C-terminal domain (CTD) of the linker
      histone (LH) is essential for chromatin compaction. However, its conformation
      upon nucleosome binding and its impact on chromatin organization remain unknown.
      Our mesoscale chromatin model with a flexible LH CTD captures a dynamic, salt
      dependent condensation mechanism driven by charge neutralization between the LH
      and linker DNA. Namely, at low salt concentration, CTD condenses, but LH only
      interacts with the nucleosome and one linker DNA, resulting in a semi-open
      nucleosome configuration; at higher salt, LH interacts with the nucleosome and
      two linker DNAs, promoting stem formation and chromatin compaction. CTD charge
      reduction unfolds the domain and decondenses chromatin, a mechanism in consonance
      with reduced counterion screening in vitro and phosphorylated LH in vivo.
      Divalent ions counteract this decondensation effect by maintaining nucleosome
      stems and expelling the CTDs to the fiber exterior. Additionally, we explain that
      the CTD folding depends on the chromatin fiber size, and we show that the
      asymmetric structure of the LH globular head is responsible for the uneven
      interaction observed between the LH and the linker DNAs. All these mechanisms may
      impact epigenetic regulation and higher levels of chromatin folding. 

PMID- 24906882
TI  - Analyzing ion distributions around DNA.
AB  - We present a new method for analyzing ion, or molecule, distributions around
      helical nucleic acids and illustrate the approach by analyzing data derived from
      molecular dynamics simulations. The analysis is based on the use of curvilinear
      helicoidal coordinates and leads to highly localized ion densities compared to
      those obtained by simply superposing molecular dynamics snapshots in Cartesian
      space. The results identify highly populated and sequence-dependent regions where
      ions strongly interact with the nucleic and are coupled to its conformational
      fluctuations. The data from this approach is presented as ion populations or ion
      densities (in units of molarity) and can be analyzed in radial, angular and
      longitudinal coordinates using 1D or 2D graphics. It is also possible to
      regenerate 3D densities in Cartesian space. This approach makes it easy to
      understand and compare ion distributions and also allows the calculation of
      average ion populations in any desired zone surrounding a nucleic acid without
      requiring references to its constituent atoms. The method is illustrated using
      microsecond molecular dynamics simulations for two different DNA oligomers in the
      presence of 0.15 M potassium chloride. We discuss the results in terms of
      convergence, sequence-specific ion binding and coupling with DNA conformation. 

PMID- 24906883
TI  - LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS
      L1000 gene expression signatures.
AB  - For the Library of Integrated Network-based Cellular Signatures (LINCS) project
      many gene expression signatures using the L1000 technology have been produced.
      The L1000 technology is a cost-effective method to profile gene expression in
      large scale. LINCS Canvas Browser (LCB) is an interactive HTML5 web-based
      software application that facilitates querying, browsing and interrogating many
      of the currently available LINCS L1000 data. LCB implements two compacted layered
      canvases, one to visualize clustered L1000 expression data, and the other to
      display enrichment analysis results using 30 different gene set libraries.
      Clicking on an experimental condition highlights gene-sets enriched for the
      differentially expressed genes from the selected experiment. A search interface
      allows users to input gene lists and query them against over 100 000 conditions
      to find the top matching experiments. The tool integrates many resources for an
      unprecedented potential for new discoveries in systems biology and systems
      pharmacology. The LCB application is available at
      http://www.maayanlab.net/LINCS/LCB. Customized versions will be made part of the
      http://lincscloud.org and http://lincs.hms.harvard.edu websites. 

PMID- 24906884
TI  - VarMod: modelling the functional effects of non-synonymous variants.
AB  - Unravelling the genotype-phenotype relationship in humans remains a challenging
      task in genomics studies. Recent advances in sequencing technologies mean there
      are now thousands of sequenced human genomes, revealing millions of single
      nucleotide variants (SNVs). For non-synonymous SNVs present in proteins the
      difficulties of the problem lie in first identifying those nsSNVs that result in
      a functional change in the protein among the many non-functional variants and in
      turn linking this functional change to phenotype. Here we present VarMod (Variant
      Modeller) a method that utilises both protein sequence and structural features to
      predict nsSNVs that alter protein function. VarMod develops recent observations
      that functional nsSNVs are enriched at protein-protein interfaces and protein
      ligand binding sites and uses these characteristics to make predictions. In
      benchmarking on a set of nearly 3000 nsSNVs VarMod performance is comparable to
      an existing state of the art method. The VarMod web server provides extensive
      resources to investigate the sequence and structural features associated with the
      predictions including visualisation of protein models and complexes via an
      interactive JSmol molecular viewer. VarMod is available for use at
      http://www.wasslab.org/varmod. 

PMID- 24906885
TI  - Cell cycle-dependent regulation of the RNA-binding protein Staufen1.
AB  - Staufen1 (Stau1) is a ribonucleic acid (RNA)-binding protein involved in the post
      transcriptional regulation of gene expression. Recent studies indicate that Stau1
      bound messenger RNAs (mRNAs) mainly code for proteins involved in transcription
      and cell cycle control. Consistently, we report here that Stau1 abundance
      fluctuates through the cell cycle in HCT116 and U2OS cells: it is high from the S
      phase to the onset of mitosis and rapidly decreases as cells transit through
      mitosis. Stau1 down-regulation is mediated by the ubiquitin-proteasome system and
      the E3 ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Stau1
      interacts with the APC/C co-activators Cdh1 and Cdc20 via its first 88 N-terminal
      amino acids. The importance of controlling Stau155 levels is underscored by the
      observation that its overexpression affects mitosis entry and impairs
      proliferation of transformed cells. Microarray analyses identified 275 Stau1(55)
      bound mRNAs in prometaphase cells, an early mitotic step that just precedes Stau1
      degradation. Interestingly, several of these mRNAs are more abundant in Stau155
      containing complexes in cells arrested in prometaphase than in asynchronous
      cells. Our results point out for the first time to the possibility that Stau1
      participates in a mechanism of post-transcriptional regulation of gene expression
      that is linked to cell cycle progression in cancer cells.

PMID- 24906886
TI  - MicroRNA-363 negatively regulates the left ventricular determining transcription
      factor HAND1 in human embryonic stem cell-derived cardiomyocytes.
AB  - INTRODUCTION: Posttranscriptional control of mRNA by microRNA (miRNA) has been
      implicated in the regulation of diverse biologic processes from directed
      differentiation of stem cells through organism development. We describe a unique
      pathway by which miRNA regulates the specialized differentiation of cardiomyocyte
      (CM) subtypes. METHODS: We differentiated human embryonic stem cells (hESCs) to
      cardiac progenitor cells and functional CMs, and characterized the regulated
      expression of specific miRNAs that target transcriptional regulators of
      left/right ventricular-subtype specification. RESULTS: From >900 known human
      miRNAs in hESC-derived cardiac progenitor cells and functional CMs, a subset of
      differentially expressed cardiac miRNAs was identified, and in silico analysis
      predicted highly conserved binding sites in the 3'-untranslated regions (3'UTRs)
      of Hand-and-neural-crest-derivative-expressed (HAND) genes 1 and 2 that are
      involved in left and right ventricular development. We studied the temporal and
      spatial expression patterns of four miRNAs in differentiating hESCs, and found
      that expression of miRNA (miR)-363, miR-367, miR-181a, and miR-181c was specific
      for stage and site. Further analysis showed that miR-363 overexpression resulted
      in downregulation of HAND1 mRNA and protein levels. A dual luciferase reporter
      assay demonstrated functional interaction of miR-363 with the full-length 3'UTR
      of HAND1. Expression of anti-miR-363 in-vitro resulted in enrichment for HAND1
      expressing CM subtype populations. We also showed that BMP4 treatment induced the
      expression of HAND2 with less effect on HAND1, whereas miR-363 overexpression
      selectively inhibited HAND1. CONCLUSIONS: These data show that miR-363 negatively
      regulates the expression of HAND1 and suggest that suppression of miR-363 could
      provide a novel strategy for generating functional left-ventricular CMs.

PMID- 24906887
TI  - CO2 acquisition in Chlamydomonas acidophila is influenced mainly by CO2, not
      phosphorus, availability.
AB  - The extremophilic green microalga Chlamydomonas acidophila grows in very acidic
      waters (pH 2.3-3.4), where CO2 is the sole inorganic carbon source. Previous work
      has revealed that the species can accumulate inorganic carbon (Ci) and exhibits
      high affinity CO2 utilization under low-CO2 (air-equilibrium) conditions, similar
      to organisms with an active CO2 concentrating mechanism (CCM), whereas both
      processes are down-regulated under high CO2 (4.5 % CO2) conditions. Responses of
      this species to phosphorus (Pi)-limited conditions suggested a contrasting
      regulation of the CCM characteristics. Therefore, we measured external carbonic
      anhydrase (CAext) activities and protein expression (CAH1), the internal pH, Ci
      accumulation, and CO2-utilization in cells adapted to high or low CO2 under Pi
      replete and Pi-limited conditions. Results reveal that C. acidophila expressed
      CAext activity and expressed a protein cross-reacting with CAH1 (the CAext from
      Chlamydomonas reinhardtii). Although the function of this CA remains unclear,
      CAext activity and high affinity CO2 utilization were the highest under low CO2
      conditions. C. acidophila accumulated Ci and expressed the CAH1 protein under all
      conditions tested, and C. reinhardtii also contained substantial amounts of CAH1
      protein under Pi-limitation. In conclusion, Ci utilization is optimized in C.
      acidophila under ecologically relevant conditions, which may enable optimal
      survival in its extreme Ci- and Pi-limited habitat. The exact physiological and
      biochemical acclimation remains to be further studied. 

PMID- 24906888
TI  - Unusual features of the high light acclimation of Chromera velia.
AB  - In the present study, the high light (HL) acclimation of Chromera velia
      (Chromerida) was studied. HL-grown cells exhibited an increased cell volume and
      dry weight compared to cells grown at medium light (ML). The chlorophyll (Chl) a
      specific absorption spectra ([Formula: see text]) of the HL cells showed an
      increased absorption efficiency over a wavelength range from 400 to 750 nm,
      possibly due to differences in the packaging of Chl a molecules. In HL cells, the
      size of the violaxanthin (V) cycle pigment pool was strongly increased. Despite a
      higher concentration of de-epoxidized V cycle pigments, non-photochemical
      quenching (NPQ) of the HL cells was slightly reduced compared to ML cells. The
      analysis of NPQ recovery during low light (LL) after a short illumination with
      excess light showed a fast NPQ relaxation and zeaxanthin epoxidation.
      Purification of the pigment-protein complexes demonstrated that the HL
      synthesized V was associated with the chromera light-harvesting complex (CLH).
      However, the difference absorption spectrum of HL minus ML CLH, together with the
      77 K fluorescence excitation spectra, suggested that the additional V was not
      protein bound but localized in a lipid phase associated with the CLH. The
      polypeptide analysis of the pigment-protein complexes showed that one out of
      three known LHCr proteins was associated in higher concentration with photosystem
      I in the HL cells, whereas in ML cells, it was enriched in the CLH fraction. In
      conclusion, the acclimation of C. velia to HL illumination shows features that
      are comparable to those of diatoms, while other characteristics more closely
      resemble those of higher plants and green algae. 

PMID- 24906889
TI  - In a daily time-place learning task, time is only used as a discriminative
      stimulus if each daily session is associated with a distinct spatial location.
AB  - It is difficult for rats to acquire daily time-place (TP) learning tasks. One
      theory suggests that rats do not use time of day as a stimulus signaling a
      specific response. In the present study, we tested rats' ability to use time of
      day as a discriminative stimulus. A fixed-interval procedure was used in which
      one lever provided reinforcement on a FI-5-s schedule in morning sessions, and
      the same lever provided reinforcement on a FI-30-s schedule in afternoon
      sessions. Because only one place was used in this paradigm, the rats could only
      use time of day to acquire the task. Mean responses during the first 5 s of the
      first trial in each session indicated that the rats did not discriminate between
      the two sessions. In Phase II, a different lever location was used for each of
      the two daily sessions, which meant that both spatial and temporal information
      could be used to acquire the task. The rats readily acquired the task in this
      phase, and probe trials indicated that the rats were using a combination of
      spatial and temporal information to discriminate between the two different trial
      types. When the spatial cue was removed in Phase III, rats no longer
      discriminated the two sessions, suggesting that time can only be used as a
      discriminative stimulus when each daily session is associated with a distinct
      spatial location.

PMID- 24906890
TI  - Enhanced defense against mitochondrial hydrogen peroxide attenuates age
      associated cognition decline.
AB  - Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's
      disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial
      antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of
      mitochondrial H2O2 in age-associated cognitive decline, we compared cognition
      between aged (17-19 months) APP transgenic mice and APP/Prdx3 double transgenic
      mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice
      (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that
      was correlated with reduced brain amyloid beta levels and decreased amyloid beta
      production. Old TG mice also showed significantly increased cognitive ability
      compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced
      mitochondrial oxidative stress and increased mitochondrial function. Moreover,
      CREB signaling, a signaling pathway important for cognition was enhanced in both
      aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2
      is a key culprit of age-associated cognitive impairment, and that a reduction of
      mitochondrial H2O2 could improve cognition by maintaining mitochondrial health
      and enhancing CREB signaling.

PMID- 24906891
TI  - Distinguishing attentional gain and tuning in young and older adults.
AB  - Here we examined with functional magnetic resonance imaging (fMRI) whether
      advanced age affects 2 mechanisms of attention that are widely thought to enhance
      signal processing in the sensory neocortex: gain and tuning. Healthy young and
      older adults discriminated faces under varying levels of object competition while
      fMRI was acquired. In young adults, cortical response magnitude to attended faces
      was maintained despite increasing competition, consistent with gain. Cortical
      response selectivity, indexed from repetition suppression, also increased only
      for attended faces despite increasing competition, consistent with tuning. Older
      adults exhibited intact gain, but altered tuning, with extrastriate cortical
      tuning determined by object salience rather than attention. Moreover, the
      magnitude of this susceptibility to stimulus-driven processing was associated
      with a redistribution of attention-driven competitive processes to the frontal
      cortices. These data indicate that although both gain and tuning are modulated by
      increased perceptual competition, they are functionally dissociable in the
      extrastriate cortices, exhibit differential susceptibility to advanced aging, and
      spare the frontal cortices a considerable processing burden through early
      selection. 

PMID- 24906892
TI  - Age-related axonal swellings precede other neuropathological hallmarks in a knock
      in mouse model of Huntington's disease.
AB  - Axon degeneration precedes cell body death in many age-related neurodegenerative
      disorders, often determining symptom onset and progression. A sensitive method
      for revealing axon pathology could indicate whether this is the case also in
      Huntington's disease (HD), a fatal, devastating neurodegenerative disorder
      causing progressive deterioration of both physical and mental abilities, and
      which brain region is affected first. We studied the spatio-temporal relationship
      between axon pathology, neuronal loss, and mutant Huntingtin aggregate formation
      in HD mouse models by crossing R6/2 transgenic and HdhQ140 knock-in mice with YFP
      H mice expressing the yellow fluorescent protein in a subset of neurons. We found
      large axonal swellings developing age-dependently first in stria terminalis and
      then in corticostriatal axons of HdhQ140 mice, whereas alterations of other
      neuronal compartments could not be detected. Although mutant Huntingtin
      accumulated with age in several brain areas, inclusions in the soma did not
      correlate with swelling of the corresponding axons. Axon abnormalities were not a
      prominent feature of the rapid progressive pathology of R6/2 mice. Our findings
      in mice genetically similar to HD patients suggest that axon pathology is an
      early event in HD and indicate the importance of further studies of stria
      terminalis axons in man. 

PMID- 24906893
TI  - [Roundtables of SFTS Congress 2013: Needs, indications and safety of blood
      products; self-sufficiency in blood products].
AB  - The current issues debate brings together experts around the themes of self
      sufficiency (in its national and European aspects) and of needs in cellular blood
      products. The point of view of the manufacturer and prescribers of blood products
      are confronted. 

PMID- 24906894
TI  - Sensor grid resource management: model and implementation issues.
AB  - This paper studies optimal sensor resource management in sensor grids. We
      formalize the problem using nonlinear optimization theory, which incorporates
      sensor resource constraint, energy, and expense budget. The paper also presents a
      pricing-based iterative algorithm for sensor management which balances the sensor
      user' QoS requirements to achieve a sensor system optimization based on the
      preference of the sensor service users. The paper discusses implementation issues
      of sensor management. Simulations reveal that the proposed sensor management
      algorithms can obtain better performance than a previous approach. 

PMID- 24906895
TI  - Nonlinear control of voltage source converters in AC-DC power system.
AB  - This paper presents the design of a robust nonlinear controller for a parallel AC
      DC power system using a Lyapunov function-based sliding mode control (LYPSMC)
      strategy. The inputs for the proposed control scheme are the DC voltage and
      reactive power errors at the converter station and the active and reactive power
      errors at the inverter station of the voltage-source converter-based high voltage
      direct current transmission (VSC-HVDC) link. The stability and robust tracking of
      the system parameters are ensured by applying the Lyapunov direct method. Also
      the gains of the sliding mode control (SMC) are made adaptive using the stability
      conditions of the Lyapunov function. The proposed control strategy offers
      invariant stability to a class of systems having modeling uncertainties due to
      parameter changes and exogenous inputs. Comprehensive computer simulations are
      carried out to verify the proposed control scheme under several system
      disturbances like changes in short-circuit ratio, converter parametric changes,
      and faults on the converter and inverter buses for single generating system
      connected to the power grid in a single machine infinite-bus AC-DC network and
      also for a 3-machine two-area power system. Furthermore, a second order super
      twisting sliding mode control scheme has been presented in this paper that
      provides a higher degree of nonlinearity than the LYPSMC and damps faster the
      converter and inverter voltage and power oscillations. 

PMID- 24906896
TI  - This is a thriving field of investigation and one which is extremely effective in
      providing therapy for patients.

PMID- 24906897
TI  - Diarrhoea and pelvic irradiation: a neglected issue.

PMID- 24906898
TI  - Antiphospholipid syndrome: a recurrent cardiac thromboembolic insult in spite of
      optimal anticoagulation.

PMID- 24906899
TI  - Religion benefiting brain tumour patients: a qualitative study.
AB  - As the focus on modern neurosurgery has shifted to the realm of technological
      advancement, some patients and their loved ones still hold a strong faith in
      their religion to guide them through the process. This study aimed to determine
      whether religion as a coping mechanism was beneficial for patients before, during
      and after craniotomy. Qualitative case study methodology was used. Interviews
      were conducted with randomly selected 36 adult patients who underwent surgery for
      a benign or malignant brain tumour. Interviews were audio recorded and
      transcribed, and the data subjected to thematic analysis. Four overarching themes
      emerged from the data: (1) religion significantly benefited neurosurgical
      patients; (2) neurosurgical patients did not require a dedicated religious room
      in the hospital; (3) neurosurgical patients required religious resources such as
      leaders and/or groups; and (4) patients were not in favour of their physician
      engaging in the religious ritual. Most patients found religion to be an effective
      coping mechanism, offering them strength, comfort, and hope through the surgery.
      The findings from this study emphasize the need for including a "religious time
      out" before and after surgery and the inclusion of religious leaders/groups for
      those in favour to ensure quality care and patient satisfaction. 

PMID- 24906900
TI  - Prevalence of difficult airway predictors in cases of failed prehospital
      endotracheal intubation.
AB  - BACKGROUND: Difficult airway predictors (DAPs) are associated with failed
      endotracheal intubation (ETI) in the emergency department (ED). However, little
      is known about the relationship between DAPs and failed prehospital ETI.
      OBJECTIVE: Our aim was to determine the prevalence of common DAPs among failed
      prehospital intubations. METHODS: We reviewed a quality-improvement database,
      including all cases of ETI in a single ED, over 3 years. Failed prehospital (FP)
      ETI was defined as a case brought to the ED after attempted prehospital ETI, but
      bag-valve-mask ventilation, need for a rescue airway (supraglottic device,
      cricothyrotomy, etc.), or esophageal intubation was discovered at the ED.
      Physicians performing ETI evaluated each case for the presence of DAPs, including
      blood/emesis, facial/neck trauma, airway edema, spinal immobilization, short
      neck, and tongue enlargement. RESULTS: There were a total of 1377 ED ETIs and 161
      had an FP-ETI (11.8%). Prevalence of DAPs in cases with FP-ETI was obesity 13.0%,
      large tongue 18.0%, short neck 13%, small mandible 4.3%, cervical immobility
      49.7%, blood in airway 57.8%, vomitus in airway 23.0%, airway edema 12.4%, and
      facial or neck trauma 32.9%. The number of cases with FP-ETI and 0, 1, 2, 3, or 4
      or more DAPs per case was 22 (13.6%), 43 (26.7%), 23 (24.3%), 42 (26.1%), and 31
      (19.3%), respectively. CONCLUSIONS: DAPs are common in cases of FP-ETI. Some of
      these factors may be associated with FP-ETI. Additional study is needed to
      determine if DAPs can be used to identify patients that are difficult to intubate
      in the field.

PMID- 24906901
TI  - Impact of community based, specialist palliative care teams on hospitalisations
      and emergency department visits late in life and hospital deaths: a pooled
      analysis.
AB  - OBJECTIVE: To determine the pooled effect of exposure to one of 11 specialist
      palliative care teams providing services in patients' homes. DESIGN: Pooled
      analysis of a retrospective cohort study. SETTING: Ontario, Canada. PARTICIPANTS:
      3109 patients who received care from specialist palliative care teams in 2009-11
      (exposed) matched by propensity score to 3109 patients who received usual care
      (unexposed). INTERVENTION: The palliative care teams studied served different
      geographies and varied in team composition and size but had the same core team
      members and role: a core group of palliative care physicians, nurses, and family
      physicians who provide integrated palliative care to patients in their homes. The
      teams' role was to manage symptoms, provide education and care, coordinate
      services, and be available without interruption regardless of time or day. MAIN
      OUTCOME MEASURES: Patients (a) being in hospital in the last two weeks of life;
      (b) having an emergency department visit in the last two weeks of life; or (c)
      dying in hospital. RESULTS: In both exposed and unexposed groups, about 80% had
      cancer and 78% received end of life homecare services for the same average
      duration. Across all palliative care teams, 970 (31.2%) of the exposed group were
      in hospital and 896 (28.9%) had an emergency department visit in the last two
      weeks of life respectively, compared with 1219 (39.3%) and 1070 (34.5%) of the
      unexposed group (P<0.001). The pooled relative risks of being in hospital and
      having an emergency department visit in late life comparing exposed versus
      unexposed were 0.68 (95% confidence interval 0.61 to 0.76) and 0.77 (0.69 to
      0.86) respectively. Fewer exposed than unexposed patients died in hospital (503
      (16.2%) v 887 (28.6%), P<0.001), and the pooled relative risk of dying in
      hospital was 0.46 (0.40 to 0.52). CONCLUSIONS: Community based specialist
      palliative care teams, despite variation in team composition and geographies,
      were effective at reducing acute care use and hospital deaths at the end of life.

PMID- 24906902
TI  - Hypertrophic changes of the teres minor muscle in rotator cuff tears:
      quantitative evaluation by magnetic resonance imaging.
AB  - BACKGROUND: Few reports have assessed the teres minor (TM) muscle in rotator cuff
      tears. This study aimed to quantitatively analyze the morphologic changes of the
      TM muscle in patients with or without rotator cuff tears by magnetic resonance
      imaging (MRI). METHODS: This retrospective study consisted of 279 subjects
      classified on the basis of interpretations of conventional MRI observations into
      6 groups: no cuff tear; partial-thickness supraspinatus (SSP) tear; full
      thickness SSP tear; SSP and subscapularis tears; SSP and infraspinatus (ISP)
      tears; and SSP, ISP, and subscapularis tears. With use of ImageJ software
      (National Institutes of Health, Bethesda, MD, USA) for oblique sagittal MRI, we
      measured the areas of ISP, TM, and anatomic external rotation (ISP + TM) muscles
      on the most lateral side in which the scapular spine was in contact with the
      scapular body. The occupational ratios of the TM muscle area to the anatomic
      external rotation muscle area were calculated. Ratios above the maximum of the
      95% confidence intervals of the occupational ratio in the no-tear group were
      defined as hypertrophy of the TM muscle. RESULTS: Occupational ratios of the TM
      muscle in the no-tear group followed a normal distribution, and ratios >0.288
      were defined as hypertrophic. Hypertrophic changes of the TM muscle were
      confirmed in rotator cuff tears involving the ISP tendon. A negative correlation
      was found between the occupational ratios of TM and ISP (P < .001). CONCLUSION:
      The TM muscle appeared hypertrophic in rotator cuff tears involving the ISP, and
      the progression of ISP muscle atrophy seemed to induce the development of this
      compensatory hypertrophy.

PMID- 24906903
TI  - The outcome of total elbow arthroplasty in juvenile idiopathic arthritis
      (juvenile rheumatoid arthritis) patients.
AB  - BACKGROUND: Elbow prosthetic replacement in patients with juvenile idiopathic
      arthritis (JIA) can be complicated and technically challenging. Thus, we sought
      to evaluate the clinical benefit and the prosthetic longevity of primary
      semiconstrained linked total elbow arthroplasty (TEA) performed to treat these
      patients. METHODS: Between 1983 and 2005, 29 elbows in 24 patients (20 women and
      4 men) had been replaced because of JIA. The mean age was 37 years (range, 24-68
      years). Because of underlying deformity, the implant contour was modified for 9
      elbows (31%) and a customized implant was inserted in 5 elbows (17%). The mean
      follow-up duration was 10.5 years (range, 4.6-20.1 years). RESULTS: During the
      follow-up period, 8 elbows underwent reoperation, including 6 (21%) that
      underwent implant revision. At most recent follow-up, 22 elbows (76%)
      subjectively had a satisfactory overall functional result. The mean Mayo Elbow
      Performance Score was 78 points (range, 50-100 points), with 18 elbows graded as
      having an excellent or good result. Compared with preoperative range of motion,
      the mean extension-flexion arc improved from 65 degrees  +/- 44 degrees  to 89
      degrees  +/- 35 degrees  (P = .01), mean flexion improved from 113 degrees  +/-
      23 degrees  to 126 degrees  +/- 26 degrees  (P = .02), and mean extension
      improved from 48 degrees  +/- 25 degrees  to 37 degrees  +/- 26 degrees  (P =
      .08). By use of the Kaplan-Meier survivorship method, the rate of TEA survival
      from any revision was 96.4% (95% confidence interval, 89.8%-100%) and 79.9% (95%
      confidence interval, 65.1%-97.5%) at 5 years and 10 years, respectively.
      CONCLUSION: Primary TEA for JIA patients is technically challenging and
      frequently requires implant modification or custom designs. These patients might
      have high complication and revision rates. However, most benefit from the
      intervention for a long term.

PMID- 24906904
TI  - The association between body fat and rotator cuff tear: the influence on rotator
      cuff tear sizes.
AB  - BACKGROUND: Rotator cuff tear (RCT) has a multifactorial etiology. We
      hypothesized that obesity may increase the risk of RCT and influence tear size.
      MATERIALS AND METHODS: A case-control design study was used. We studied 381
      consecutive patients (180 men, 201 women; mean age +/- standard deviation, 65.5
      +/- 8.52 years; range, 43-78 years) who underwent arthroscopic rotator cuff
      repair. Tear size was determined intraoperatively. The control group included 220
      subjects (103 men, 117 women; mean age +/- standard deviation, 65.16 +/- 7.24
      years; range, 42-77 years) with no RCT. Body weight, height, and bicipital,
      tricipital, subscapularis, and suprailiac skinfolds of all participants were
      measured to obtain body mass index (BMI) and the percentage of body fat (%BF).
      For the purposes of the study, the 601 participants were divided into 2 groups by
      BMI (group A, BMI >= 25; group B, BMI < 25). The odds ratios (ORs) were
      calculated to investigate whether adiposity affects the risk of RCT. Data were
      stratified according to gender and age. Multiple linear regression analyses were
      applied to explore the association between obesity and tear size. RESULTS: The
      highest ORs for both men (OR, 2.49; 95% confidence interval, 1.41-3.90; P =
      .0037) and women (OR, 2.31; 95% confidence interval, 1.38-3.62; P = .0071) were
      for individuals with a BMI >= 30; 69% (N = 303) of group A and 48% (N = 78) of
      group B had RCTs. Patients with RCT had a BMI higher than that of subjects with
      no RCT in both groups (P = .031, group A; P = .02, group B). BMI and %BF
      significantly increased from patients with a small tear (BMI, 27.85; %BF, 37.63)
      to those with a massive RCT (BMI, 29.93; %BF, 39.43). Significant differences
      were found (P = .004; P = .031). CONCLUSIONS: Our results provide evidence that
      obesity, measured through BMI and %BF, is a significant risk factor for the
      occurrence and severity of RCT.

PMID- 24906906
TI  - Prevalence of asymptomatic lower limb venous thrombosis in infertile women with
      thrombophilic disorders.
AB  - OBJECTIVE: We sought to assess the prevalence of asymptomatic venous thrombosis
      in infertile women with thrombophilic disorders (TDs). METHODS AND RESULTS: A
      total of 73 infertile women with TDs underwent duplex ultrasound scan to evaluate
      superficial and deep venous circulation of lower limbs. A control group of 35
      infertile women without TDs was included. A single TD was found in 13 (17.8%)
      subjects, and 40 (54.8%) women presented a combined defect (more than three
      alterations). No residual mural thrombosis (RT) was noted in any deep veins. We
      found RT in 48 (65.8%) patients of TD group, while no RT was found in the control
      group (p < 0.0001). None of the clinical and prothrombotic factors were
      predictors of RT (all p > 0.20), and frequency of TD did not correlate with multi
      vessel RT (p = 0.252). CONCLUSIONS: No signs of deep vein thrombosis but high
      prevalence of superficial RT is present in infertile women with TDs. Further
      studies are needed to assess the prognostic value of our findings.

PMID- 24906907
TI  - Saphenous vein stripping surgical technique and frequency of saphenous nerve
      injury.
AB  - OBJECTIVES: Saphenous nerve injury is the most common complication after surgical
      treatment of varicose veins. The aim of this study was to establish its frequency
      at great saphenous vein long stripping when four methods of surgery were applied.
      METHODS: Eighty patients were divided into four groups depending on different
      stripping methods. Sensory transmission in saphenous nerve and sensory perception
      of shank were examined before surgery and two weeks, three and six months
      afterwards with clinical neurophysiology methods. RESULTS: In 36% of patients,
      surgeries caused the injury of saphenous nerve mainly by proximal stripping
      without invagination (65%, group I). Transmission disturbances ceased completely
      after three months in patients undergoing distal stripping with invagination
      (group IV), while in group I they persisted for six months in 35%. Group IV
      patients were the least injured and group I the most. CONCLUSION:
      Neurophysiological findings may suggest that distal stripping with vein
      invagination gives the best saphenous nerve sparing.

PMID- 24906905
TI  - Variations in the slope of the psychometric functions for speech intelligibility:
      a systematic survey.
AB  - Although many studies have looked at the effects of different listening
      conditions on the intelligibility of speech, their analyses have often
      concentrated on changes to a single value on the psychometric function, namely,
      the threshold. Far less commonly has the slope of the psychometric function, that
      is, the rate at which intelligibility changes with level, been considered. The
      slope of the function is crucial because it is the slope, rather than the
      threshold, that determines the improvement in intelligibility caused by any given
      improvement in signal-to-noise ratio by, for instance, a hearing aid. The aim of
      the current study was to systematically survey and reanalyze the psychometric
      function data available in the literature in an attempt to quantify the range of
      slope changes across studies and to identify listening conditions that affect the
      slope of the psychometric function. The data for 885 individual psychometric
      functions, taken from 139 different studies, were fitted with a common logistic
      equation from which the slope was calculated. Large variations in slope across
      studies were found, with slope values ranging from as shallow as 1% per dB to as
      steep as 44% per dB (median = 6.6% per dB), suggesting that the perceptual
      benefit offered by an improvement in signal-to-noise ratio depends greatly on
      listening environment. The type and number of maskers used were found to be major
      factors on the value of the slope of the psychometric function while other minor
      effects of target predictability, target corpus, and target/masker similarity
      were also found. 

PMID- 24906908
TI  - "Pregnancy in adult-onset idiopathic inflammatory myopathy": report from a cohort
      of myositis patients from a single center.
AB  - BACKGROUND AND PURPOSE: Idiopathic inflammatory myopathies (IIM) are systemic
      diseases, characterized by the presence of an inflammatory muscle infiltrate.
      Although more frequent in women, its relationship with pregnancy has not been
      extensively studied. Our goal was to analyze the interaction between pregnancy
      and myositis in a cohort of IIM women from a single center. METHODS: A total of
      51 patients from a historical cohort of IIM diagnosed between 1983 and 2013 were
      interviewed with a specific questionnaire. Comparisons between pregnancies
      occurring before and after the onset of the disease were performed using
      generalized mixed-effect models with normal and binomial distributions adjusted
      for confounding factors and clustering. RESULTS: A total of 102 pregnancies from
      51 patients (41 with dermatomyositis and 10 with polymyositis) were analyzed. A
      total of 14 pregnancies from 8 patients occurred after disease onset;
      statistically significant (p = 0.02) clinical improvement during gestation was
      evident in 7 pregnancies (4 patients), 5 of them (from 2 patients) experienced a
      relapse of IIM symptoms afterwards, while in the rest, there was no influence of
      pregnancy on the disease. No disease flare associated with pregnancy was
      observed. Two patients were diagnosed within the first 6 months after delivery
      and none during pregnancy. No evidence was found to support pregnancy as a
      trigger for myopathy (p = 0.71). CONCLUSIONS: Pregnancy does not seem to carry a
      worse prognosis for the mother nor for the fetus in patients with IIM; on the
      contrary, nearly half of the patients in our series improved clinically when they
      became pregnant, a relapse of IIM symptoms being common afterwards. Pregnancy
      does not appear to be a trigger for IIM.

PMID- 24906909
TI  - Beneficial Effects of Pranic Meditation on the Mental Health and Quality of Life
      of Breast Cancer Survivors.
AB  - BACKGROUND: Breast cancer survivors frequently present long-lasting impairments,
      caused either by the disease or its treatment, capable of compromising their
      emotional health and quality of life. Meditation appears to be a valuable
      complementary measure for overcoming some of these impairments. The purpose of
      the present investigation was to assess the effect of pranic meditation on the
      quality of life and mental health of breast cancer survivors. DESIGN: This study
      was a prospective single-arm observational study using before and after
      measurements. METHODS: The subjects were 75 women submitted either to breast
      cancer therapy or to posttherapy control who agreed to practice pranic meditation
      for 20 minutes, twice a day, during 8 weeks, after receiving a formal training.
      The quality of life of the practitioners was assessed by the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC BR
      023 questionnaires, and the mental health status by the Goldberg's General Health
      Questionnaire. RESULTS: After 8 weeks of pranic meditation practice, the subjects
      showed a significant improvement of their quality of life scores that included
      physical (P = .0007), role (P = .01), emotional (P = .002), and social
      functioning (P = .004), as well as global health status (P = .005), fatigue (P <
      .0001), pain (P = .007), sleep disturbances (P = .01), body image (P = .001), arm
      symptoms (P = .007), and breast symptoms (P = .002). They also showed a reduction
      of the side effects of systemic therapy (P = .02) and being upset by hair loss (P
      = .02). Moreover, meditation was associated with improvement of the mental health
      parameters of the practitioners that included psychic stress (P = .001), death
      ideation (P = .02), performance diffidence (P = .001), psychosomatic disorders (P
      = .02), and severity of mental disorders (P = .0003). The extension of the
      meditation period from 8 to 15 weeks caused no substantial extra benefits in
      practitioners. CONCLUSIONS: The results of this pilot study showed that breast
      cancer survivors presented significant benefits related to their mental health
      and quality of life scores after a short period of practice of pranic meditation,
      consisting of simple and easy-to-learn exercises. However, because of the
      limitations of the study, further research is required using a more rigorous
      experimental design to ascertain whether pranic meditation may be an acceptable
      adjunct therapy for cancer patients.

PMID- 24906910
TI  - A clinical protocol demonstrating rapid, safe, and effective treatment of vitamin
      D deficiency: a potential role in oncology alongside conventional treatment.
AB  - Vitamin D status has importance in the prevention and treatment of many
      malignancies. Patients with breast, colon, and lung malignancies with higher
      vitamin D status at the onset of treatment have an improved prognosis compared
      with those patients with a lower vitamin D status. Methods to improve vitamin D
      status are often unreliable and take time, often months, to be successful. A
      method that improves and normalizes the vitamin D status safely, quickly (within
      1-2 weeks), and reliably is described herein. The use of this method will allow
      testing of the hypothesis that improving the vitamin D status of patients with
      various malignancies before treatment is initiated will improve their outcome. 

PMID- 24906911
TI  - Thickness related textural properties of retinal nerve fiber layer in color
      fundus images.
AB  - Images of ocular fundus are routinely utilized in ophthalmology. Since an
      examination using fundus camera is relatively fast and cheap procedure, it can be
      used as a proper diagnostic tool for screening of retinal diseases such as the
      glaucoma. One of the glaucoma symptoms is progressive atrophy of the retinal
      nerve fiber layer (RNFL) resulting in variations of the RNFL thickness. Here, we
      introduce a novel approach to capture these variations using computer-aided
      analysis of the RNFL textural appearance in standard and easily available color
      fundus images. The proposed method uses the features based on Gaussian Markov
      random fields and local binary patterns, together with various regression models
      for prediction of the RNFL thickness. The approach allows description of the
      changes in RNFL texture, directly reflecting variations in the RNFL thickness.
      Evaluation of the method is carried out on 16 normal ("healthy") and 8
      glaucomatous eyes. We achieved significant correlation (normals: rho=0.72+/-0.14;
      p?0.05, glaucomatous: rho=0.58+/-0.10; p?0.05) between values of the model
      predicted output and the RNFL thickness measured by optical coherence tomography,
      which is currently regarded as a standard glaucoma assessment device. The
      evaluation thus revealed good applicability of the proposed approach to measure
      possible RNFL thinning.

PMID- 24906912
TI  - Population-specific common SNPs reflect demographic histories and highlight
      regions of genomic plasticity with functional relevance.
AB  - BACKGROUND: Population differentiation is the result of demographic and
      evolutionary forces. Whole genome datasets from the 1000 Genomes Project (October
      2012) provide an unbiased view of genetic variation across populations from
      Europe, Asia, Africa and the Americas. Common population-specific SNPs (MAF >
      0.05) reflect a deep history and may have important consequences for health and
      wellbeing. Their interpretation is contextualised by currently available genome
      data. RESULTS: The identification of common population-specific (CPS) variants
      (SNPs and SSV) is influenced by admixture and the sample size under
      investigation. Nine of the populations in the 1000 Genomes Project (2 African, 2
      Asian (including a merged Chinese group) and 5 European) revealed that the
      African populations (LWK and YRI), followed by the Japanese (JPT) have the
      highest number of CPS SNPs, in concordance with their histories and given the
      populations studied. Using two methods, sliding 50-SNP and 5-kb windows, the CPS
      SNPs showed distinct clustering across large genome segments and little overlap
      of clusters between populations. iHS enrichment score and the population branch
      statistic (PBS) analyses suggest that selective sweeps are unlikely to account
      for the clustering and population specificity. Of interest is the association of
      clusters close to recombination hotspots. Functional analysis of genes associated
      with the CPS SNPs revealed over-representation of genes in pathways associated
      with neuronal development, including axonal guidance signalling and CREB
      signalling in neurones. CONCLUSIONS: Common population-specific SNPs are non
      randomly distributed throughout the genome and are significantly associated with
      recombination hotspots. Since the variant alleles of most CPS SNPs are the
      derived allele, they likely arose in the specific population after a split from a
      common ancestor. Their proximity to genes involved in specific pathways,
      including neuronal development, suggests evolutionary plasticity of selected
      genomic regions. Contrary to expectation, selective sweeps did not play a large
      role in the persistence of population-specific variation. This suggests a
      stochastic process towards population-specific variation which reflects
      demographic histories and may have some interesting implications for health and
      susceptibility to disease.

PMID- 24906913
TI  - Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all
      mitochondria created equal?
AB  - Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle
      mitochondrial respiration. Therefore, the present study examined mitochondrial
      respiratory rates in smooth muscle of healthy human feed arteries and compared
      with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth
      muscles were harvested from a total of 22 subjects (53 +/- 6 yr), and
      mitochondrial respiration was assessed in permeabilized fibers. Complex I + II,
      state 3 respiration, an index of oxidative phosphorylation capacity, fell
      progressively from cardiac to skeletal to smooth muscles (54 +/- 1, 39 +/- 4, and
      15 +/- 1 pmol.s(-1).mg(-1), P < 0.05, respectively). Citrate synthase (CS)
      activity, an index of mitochondrial density, also fell progressively from cardiac
      to skeletal to smooth muscles (222 +/- 13, 115 +/- 2, and 48 +/- 2 MUmol.g(
      1).min(-1), P < 0.05, respectively). Thus, when respiration rates were normalized
      by CS (respiration per mitochondrial content), oxidative phosphorylation capacity
      was no longer different between the three muscle types. Interestingly, complex I
      state 2 normalized for CS activity, an index of nonphosphorylating respiration
      per mitochondrial content, increased progressively from cardiac to skeletal to
      smooth muscles, such that the respiratory control ratio, state 3/state 2
      respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3
      +/- 0.7, 3.2 +/- 0.4, and 1.6 +/- 0.3 pmol.s(-1).mg(-1), P < 0.05, respectively).
      Thus, although oxidative phosphorylation capacity per mitochondrial content in
      cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal,
      the contrasting respiratory control ratio and nonphosphorylating respiration
      highlight the existence of intrinsic functional differences between these muscle
      mitochondria. This likely influences the efficiency of oxidative phosphorylation
      and could potentially alter ROS production. 

PMID- 24906915
TI  - Retrograde shear rate in formerly preeclamptic and healthy women before and after
      exercise training: relationship with endothelial function.
AB  - Blood flow patterns in conduit arteries characterized by high levels of
      retrograde shear stress can be detrimental for vascular health. In this study we
      examined whether retrograde shear rate and endothelial function are related in
      healthy and formerly preeclamptic (PE) women and whether this relationship is
      altered by exercise training. Formerly PE women (32 +/- 4 yr, n = 20) and
      controls (32 +/- 4 yr, n = 20), all 6-12 mo postpartum, performed 12-wk aerobic
      exercise training. We measured brachial artery shear rate (SR) and endothelial
      function by flow-mediated dilation (FMD, echo-Doppler). We additionally performed
      power spectral analysis of heart rate variability and calculated low
      frequency/high-frequency (LF/HF) ratio. Antegrade SR was not different between
      groups, while retrograde SR was significantly higher and FMD% lower in PE women
      compared with controls (both P < 0.05). Retrograde shear correlated strongly with
      FMD% in PE women and controls (P < 0.05). LF/HF ratio inversely correlated with
      brachial artery retrograde SR and FMD% (both P < 0.05) in PE women and controls.
      Exercise training reduced retrograde shear, improved FMD%, and reduced LF/HF
      ratios similarly in both groups (all P < 0.05). Training-induced changes in
      retrograde SR correlated with changes in FMD% and LF/HF ratio. A higher brachial
      artery retrograde SR relates to lower brachial artery endothelial function, in
      both controls and formerly PE women. Exercise training improves retrograde SR,
      while the magnitude of this change correlated strongly with improvements in FMD
      and reductions in LF/HF ratio. Therefore, the impact of PE and exercise training
      on endothelial health may, at least partly, be related to retrograde shear rate. 

PMID- 24906914
TI  - Nuclear RhoA signaling regulates MRTF-dependent SMC-specific transcription.
AB  - We have previously shown that RhoA-mediated actin polymerization stimulates
      smooth muscle cell (SMC)-specific transcription by regulating the nuclear
      localization of the myocardin-related transcription factors (MRTFs). On the basis
      of the recent demonstration that nuclear G-actin regulates MRTF nuclear export
      and observations from our laboratory and others that the RhoA effector, mDia2,
      shuttles between the nucleus and cytoplasm, we investigated whether nuclear RhoA
      signaling plays a role in regulating MRTF activity. We identified sequences that
      control mDia2 nuclear-cytoplasmic shuttling and used mDia2 variants to
      demonstrate that the ability of mDia2 to fully stimulate MRTF nuclear
      accumulation and SMC-specific gene transcription was dependent on its
      localization to the nucleus. To test whether RhoA signaling promotes nuclear
      actin polymerization, we established a fluorescence recovery after photobleaching
      (FRAP)-based assay to measure green fluorescent protein-actin diffusion in the
      nuclear compartment. Nuclear actin FRAP was delayed in cells expressing nuclear
      targeted constitutively active mDia1 and mDia2 variants and in cells treated with
      the polymerization inducer, jasplakinolide. In contrast, FRAP was enhanced in
      cells expressing a nuclear-targeted variant of mDia that inhibits both mDia1 and
      mDia2. Treatment of 10T1/2 cells with sphingosine 1-phosphate induced RhoA
      activity in the nucleus and forced nuclear localization of RhoA or the Rho
      specific guanine nucleotide exchange factor (GEF), leukemia-associated RhoGEF,
      enhanced the ability of these proteins to stimulate MRTF activity. Taken
      together, these data support the emerging idea that RhoA-dependent nuclear actin
      polymerization has important effects on transcription and nuclear structure. 

PMID- 24906916
TI  - cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary
      arteries.
AB  - cGMP is considered the only mediator synthesized by soluble guanylyl cyclase
      (sGC) in response to nitric oxide (NO). However, purified sGC can synthesize
      several other cyclic nucleotides, including inosine 3',5'-cyclic monophosphate
      (cIMP). The present study was designed to determine the role of cIMP in hypoxic
      contractions of isolated porcine coronary arteries. Vascular responses were
      examined by measuring isometric tension. Cyclic nucleotides were assayed by HPLC
      tandem mass spectroscopy. Rho kinase (ROCK) activity was determined by measuring
      the phosphorylation of myosin phosphatase target subunit 1 using Western blot
      analysis and an ELISA kit. The level of cIMP, but not that of cGMP, was elevated
      by hypoxia in arteries with, but not in those without, endothelium [except if
      treated with diethylenetriamine (DETA) NONOate]; the increases in cIMP were
      inhibited by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one
      (ODQ). Hypoxia (Po2: 25-30 mmHg) augmented contractions of arteries with and
      without endothelium if treated with DETA NONOate; these hypoxic contractions were
      blocked by ODQ. In arteries without endothelium, hypoxic augmentation of
      contraction was also obtained with exogenous cIMP. In arteries with endothelium,
      hypoxic augmentation of contraction was further enhanced by inosine 5'
      triphosphate, the precursor for cIMP. The augmentation of contraction caused by
      hypoxia or cIMP was accompanied by increased phosphorylation of myosin
      phosphatase target subunit 1 at Thr(853), which was prevented by the ROCK
      inhibitor Y-27632. ROCK activity in the supernatant of isolated arteries was
      stimulated by cIMP in a concentration-dependent fashion. These results
      demonstrate that cIMP synthesized by sGC is the likely mediator of hypoxic
      augmentation of coronary vasoconstriction, in part by activating ROCK. 

PMID- 24906917
TI  - An optimized method for estimating the tidal volume from intracardiac or body
      surface electrocardiographic signals: implications for estimating minute
      ventilation.
AB  - The ability to accurately monitor tidal volume (TV) from electrocardiographic
      (ECG) signals holds significant promise for improving diagnosis treatment across
      a variety of clinical settings. The objective of this study was to develop a
      novel method for estimating the TV from ECG signals. In 10 mechanically
      ventilated swine, we collected intracardiac electrograms from catheters in the
      coronary sinus (CS), left ventricle (LV), and right ventricle (RV), as well as
      body surface electrograms, while TV was varied between 0 and 750 ml at
      respiratory rates of 7-14 breaths/min. We devised an algorithm to determine the
      optimized respirophasic modulation of the amplitude of the ECG-derived
      respiratory signal. Instantaneous measurement of respiratory modulation showed an
      absolute error of 72.55, 147.46, 85.68, 116.62, and 50.89 ml for body surface,
      CS, LV, RV, and RV-CS leads, respectively. Minute TV estimation demonstrated a
      more accurate estimation with an absolute error of 69.56, 153.39, 79.33, 122.16,
      and 48.41 ml for body surface, CS, LV, RV, and RV-CS leads, respectively. The RV
      CS and body surface leads provided the most accurate estimations that were within
      7 and 10% of the true TV, respectively. Finally, the absolute error of the
      bipolar RV-CS lead was significantly lower than any other lead configuration (P <
      0.0001). In conclusion, we have demonstrated that ECG-derived respiratory
      modulation provides an accurate estimation of the TV using intracardiac or body
      surface signals, without the need for additional hardware. 

PMID- 24906918
TI  - And the beat goes on: maintained cardiovascular function during aging in the
      longest-lived rodent, the naked mole-rat.
AB  - The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum
      lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these
      animals display attenuation of many age-associated diseases and functional
      changes until the last quartile of their MLSP. We questioned if such abilities
      would extend to cardiovascular function and structure in this species. To test
      this, we assessed cardiac functional reserve, ventricular morphology, and
      arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine
      echocardiography (3 MUg/g ip) revealed no age-associated changes in left
      ventricular (LV) function either at baseline or with exercise-like stress.
      Baseline and dobutamine-induced LV pressure parameters also did not change. Thus
      the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no
      cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional
      area or LV dimensions with age. Age-associated arterial stiffening does not occur
      since there are no changes in aortic blood pressures or pulse-wave velocity. Only
      LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P
      < 0.01). However, its effect on LV diastolic function is likely minor since NMRs
      experience attenuated age-related increases in diastolic dysfunction in
      comparison with other species. Overall, these findings conform to the negligible
      senescence phenotype, as NMRs largely stave off cardiovascular changes for at
      least 75% of their MLSP. This suggests that using a comparative strategy to find
      factors that change with age in other mammals but not NMRs could provide novel
      targets to slow or prevent cardiovascular aging in humans. 

PMID- 24906920
TI  - Cardiac responses to left ventricular pacing in hearts with normal electrical
      conduction: beneficial effect of improved filling is counteracted by
      dyssynchrony.
AB  - Cardiac resynchronization therapy (CRT) has been proposed in heart failure
      patients with narrow QRS, but the mechanism of a potential beneficial effect is
      unknown. The present study investigated the hypothesis that left ventricular (LV)
      pacing increases LV end-diastolic volume (LVEDV) by allowing the LV to start
      filling before the right ventricle (RV) during narrow QRS in an experimental
      model. LV and biventricular pacing were studied in six anesthetized dogs before
      and after the induction of LV failure. Function was evaluated by pressures and
      dimensions, and dyssynchrony was evaluated by electromyograms and deformation. In
      the nonfailing heart, LV pacing gave the LV a head start in filling relative to
      the RV (P < 0.05) and increased LVEDV (P < 0.05). The response was similar during
      LV failure when RV diastolic pressure was elevated. The pacing-induced increase
      in LVEDV was attributed to a rightward shift of the septum (P < 0.01) due to an
      increased left-to-right transseptal pressure gradient (P < 0.05). LV pacing,
      however, also induced dyssynchrony (P < 0.05) and therefore reduced LV stroke
      work (P < 0.05) during baseline, and similar results were seen in failing hearts.
      Biventricular pacing did not change LVEDV, but systolic function was impaired.
      This effect was less marked than with LV pacing. In conclusion, pacing of the LV
      lateral wall increased LVEDV by displacing the septum rightward, suggesting a
      mechanism for a favorable effect of CRT in narrow QRS. The pacing, however,
      induced dyssynchrony and therefore reduced LV systolic function. These
      observations suggest that detrimental effects should be considered when applying
      CRT in patients with narrow QRS. 

PMID- 24906919
TI  - Direct and indirect protection of right ventricular function by estrogen in an
      experimental model of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) results in right ventricular (RV)
      dysfunction and failure. Paradoxically, women are more frequently diagnosed with
      PAH but have better RV systolic function and survival rates than men. The
      mechanisms by which sex differences alter PAH outcomes remain unknown. Here, we
      sought to study the role of estrogen in RV functional remodeling in response to
      PAH. The SU5416-hypoxia (SuHx) mouse model of PAH was used. To study the role of
      estrogen, female mice were ovariectomized and then treated with estrogen or
      placebo. SuHx significantly increased RV afterload and resulted in RV
      hypertrophy. Estrogen treatment attenuated the increase in RV afterload compared
      with the untreated group (effective arterial elastance: 2.3 +/- 0.1 mmHg/MUl vs.
      3.2 +/- 0.3 mmHg/MUl), and this was linked to preserved pulmonary arterial
      compliance (compliance: 0.013 +/- 0.001 mm(2)/mmHg vs. 0.010 +/- 0.001
      mm(2)/mmHg; P < 0.05) and decreased distal muscularization. Despite lower RV
      afterload in the estrogen-treated SuHx group, RV contractility increased to a
      similar level as the placebo-treated SuHx group, suggesting an inotropic effect
      of estrogen on RV myocardium. Consequently, when compared with the placebo
      treated SuHx group, estrogen improved RV ejection fraction and cardiac output
      (ejection fraction: 57 +/- 2% vs. 44 +/- 2% and cardiac output: 9.7 +/- 0.4
      ml/min vs. 7.6 +/- 0.6 ml/min; P < 0.05). Our study demonstrates for the first
      time that estrogen protects RV function in the SuHx model of PAH in mice directly
      by stimulating RV contractility and indirectly by protecting against pulmonary
      vascular remodeling. These results underscore the therapeutic potential of
      estrogen in PAH. 

PMID- 24906922
TI  - Characterization of glucagon-like peptide 2 receptor (GLP2R) gene in chickens:
      functional analysis, tissue distribution, and developmental expression profile of
      GLP2R in embryonic intestine.
AB  - This study characterized the glucagon-like peptide 2 receptor (GLP2R) gene of
      chickens because relatively little is known about the underlying mechanism of
      GLP2 actions in nonmammalian species. With the use of reverse transcription PCR,
      we first cloned the chicken GLP2R (cGLP2R) from adult intestine, which was
      predicted to encode a 529-amino acid receptor precursor. With the use of a pGL3
      CRE luciferase reporter system, we demonstrated that cGLP2R expressed in Chinese
      hamster ovary cells could be potently activated by cGLP2 (half maximal effective
      concentration, 1.06 nM) but not by its structurally related peptides, including
      the newly identified glucagon-like peptide, indicating that cGLP2R is a
      functional receptor specific to cGLP2. Reverse transcription PCR assay revealed
      that cGLP2R mRNA was widely expressed in adult chicken tissues, including
      pancreas and various parts of the gastrointestinal tract. With the use of
      quantitative real-time reverse transcription PCR assays, we further investigated
      the mRNA expression of cGLP2R and its potential downstream mediators, epidermal
      growth factor receptor (EGFR) ligands (heparin-binding EGF-like growth factor,
      epiregulin, and amphiregulin), in the distal duodenum of developing embryos. The
      mRNA expression levels of GLP2R and EGFR ligands (heparin-binding EGF-like growth
      factor and amphiregulin) were shown to increase (P < 0.05 or 0.01) during the
      late embryonic stages (E16 and E20), implying a potential coordinated action of
      GLP2 and EGFR ligands on embryonic intestine development. Taken together, our
      findings not only establish a molecular basis to explore the physiological roles
      of GLP2 in birds, but they also provide comparative insights into the roles of
      GLP2R and its ligand in vertebrates, such as its roles in embryonic intestine
      development.

PMID- 24906923
TI  - Effects of RU486 and indomethacin on meiotic maturation, formation of
      extracellular matrix, and progesterone production by porcine oocyte-cumulus
      complexes.
AB  - This study was designed to determine whether inhibition of either cyclooxygenase
      2 (COX-2) by indomethacin or progesterone receptor (PR) by PR antagonist, RU486,
      affects oocyte maturation, progesterone production, and covalent binding between
      hyaluronan (HA) and heavy chains of inter-alpha trypsin inhibitor, as well as
      expression of cumulus expansion-associated proteins (HA-binding protein, tumor
      necrosis factor alpha-induced protein 6, pentraxin 3) in oocyte-cumulus complexes
      (OCCs). The experiments were based on freshly isolated porcine OCC cultures in
      which the consequences of PR and COX-2 inhibition on the final processes of
      oocyte maturation were determined. Granulosa cells (GCs) and OCCs were cultured
      in medium supplemented with FSH/LH (both 100 ng/mL) in the presence/absence of
      RU486 or indomethacin. Western blot analysis, (3)H-glucosamine hydrochloride
      assay, immunofluorescence, and radioimmunoassay were performed. Only treatment
      with RU486 (25 MUM) caused a decrease in the number of oocytes that reached
      germinal vesicle breakdown and metaphase II stage compared with indomethacin (100
      MUM) or FSH/LH treatment alone after 44 h. All treated OCCs synthesized an almost
      equal amount of HA. Heavy chains (of inter-alpha trypsin inhibitor)-HA covalent
      complexes were formed during in vitro FSH/LH-stimulated expansion in RU486- or
      indomethacin-treated OCCs. Follicle-stimulating hormone/LH-induced progesterone
      production by OCCs was increased in the presence of RU486 after 44 h. In
      contrast, a decrease of FSH/LH-stimulated progesterone production by GCs was
      detected in the presence of either RU486 or indomethacin after 72 h. We suggest
      that the PR-dependent pathway may be involved in the regulation of oocyte
      maturation. Both PR and COX-2 regulate FSH/LH-stimulated progesterone production
      by OCCs and GCs.

PMID- 24906921
TI  - Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti
      inflammatory effects and promotes anti-aging miRNA expression profile in
      cerebromicrovascular endothelial cells of aged rats.
AB  - In rodents, moderate caloric restriction (CR) without malnutrition exerts
      significant cerebrovascular protective effects, improving cortical microvascular
      density and endothelium-dependent vasodilation, but the underlying cellular
      mechanisms remain elusive. To elucidate the persisting effects of CR on
      cerebromicrovascular endothelial cells (CMVECs), primary CMVECs were isolated
      from young (3 mo old) and aged (24 mo old) ad libitum-fed and aged CR F344xBN
      rats. We found an age-related increase in cellular and mitochondrial oxidative
      stress, which is prevented by CR. Expression and transcriptional activity of Nrf2
      are both significantly reduced in aged CMVECs, whereas CR prevents age-related
      Nrf2 dysfunction. Expression of miR-144 was upregulated in aged CMVECs, and
      overexpression of miR-144 significantly decreased expression of Nrf2 in cells
      derived from both young animals and aged CR rats. Overexpression of a miR-144
      antagomir in aged CMVECs significantly decreases expression of miR-144 and
      upregulates Nrf2. We found that CR prevents age-related impairment of angiogenic
      processes, including cell proliferation, adhesion to collagen, and formation of
      capillary-like structures and inhibits apoptosis in CMVECs. CR also exerts
      significant anti-inflammatory effects, preventing age-related increases in the
      transcriptional activity of NF-kappaB and age-associated pro-inflammatory shift
      in the endothelial secretome. Characterization of CR-induced changes in miRNA
      expression suggests that they likely affect several critical functions in
      endothelial cell homeostasis. The predicted regulatory effects of CR-related
      differentially expressed miRNAs in aged CMVECs are consistent with the anti-aging
      endothelial effects of CR observed in vivo. Collectively, we find that CR confers
      persisting anti-oxidative, pro-angiogenic, and anti-inflammatory cellular
      effects, preserving a youthful phenotype in rat cerebromicrovascular endothelial
      cells, suggesting that through these effects CR may improve cerebrovascular
      function and prevent vascular cognitive impairment. 

PMID- 24906924
TI  - Relationship of follicle size and concentrations of estradiol among cows
      exhibiting or not exhibiting estrus during a fixed-time AI protocol.
AB  - Cows exhibiting estrus near fixed-time artificial insemination (AI) had greater
      pregnancy success than cows not showing estrus. The objective of this study was
      to determine the relationship between follicle size and peak estradiol
      concentration between cows that did or did not exhibit estrus during a fixed-time
      AI protocol. Ovulation was synchronized in beef cows by applying the CO-Synch
      protocol [GnRH (100 MUg) on day-9, prostaglandin F2alpha (PGF2alpha; 25 mg) on
      day-2, and a second injection of GnRH 48 h after PGF2alpha (day 0)] to both
      suckled (experiment 1) and nonsuckled (experiment 2) cows. Follicle size (day 0)
      and ovulation (day 2) was determined by ultrasonography. Blood samples were
      collected every 3 or 4 h beginning at the time of PGF2alpha injection (0 h).
      Estrus was detected by visual observation with the aid of estrus-detection
      patches, and cows that ovulated were classified as exhibited estrus (n = 46) or
      did not exhibit estrus (n = 63). In both suckled and nonsuckled cows, there was a
      positive relationship between all cows (P < 0.05) and among those that exhibited
      estrus (P < 0.05) between follicle size and peak estradiol concentration, but no
      linear relationship (P > 0.50) between follicle size and peak estradiol
      concentration was observed among cows not exhibiting estrus. Cows that exhibited
      estrus had greater (P < 0.01) peak estradiol concentrations than cows that did
      not exhibit estrus. Suckled cows exhibiting standing estrus had greater (P <
      0.001) preovulatory concentrations of estradiol beginning 6 h (replicate 1) or 4
      h (replicate 2) after the injection of PGF2alpha on day-2 compared with cows not
      exhibiting standing estrus. Nonsuckled cows exhibiting standing estrus had
      greater (P < 0.001) preovulatory concentrations of estradiol beginning at the
      injection of PGF2alpha on day-2 compared with cows not exhibiting standing
      estrus. Furthermore, cows that exhibited estrus had an increased (P < 0.01) rate
      in the rise in concentrations of estradiol following the PGF2alpha to peak
      estradiol than cows not exhibiting estrus. In summary, follicle diameter had a
      positive relationship with peak concentrations of estradiol, but only among cows
      that exhibited standing estrus, and estradiol increased earlier in cows that
      exhibited estrus compared with cows that did not. 

PMID- 24906925
TI  - Expression and localization of ghrelin and its functional receptor in corpus
      luteum during different stages of estrous cycle and the modulatory role of
      ghrelin on progesterone production in cultured luteal cells in buffalo.
AB  - Evidence obtained during recent years provided has insight into the regulation of
      corpus luteum (CL) development, function, and regression by locally produced
      ghrelin. The present study was carried out to evaluate the expression and
      localization of ghrelin and its receptor (GHS-R1a) in bubaline CL during
      different stages of the estrous cycle and investigate the role of ghrelin on
      progesterone (P4) production along with messenger RNA (mRNA) expression of P4
      synthesis intermediates. The mRNA and protein expression of ghrelin and GHS-R1a
      was significantly greater in mid- and late luteal phases. Both factors were
      localized in luteal cells, exclusively in the cytoplasm. Immunoreactivity of
      ghrelin and GHS-R1a was greater during mid- and late luteal phases. Luteal cells
      were cultured in vitro and treated with ghrelin each at 1, 10, and 100 ng/mL
      concentrations for 48 h after obtaining 75% to 80% confluence. At a dose of 1
      ng/mL, there was no significant difference in P4 secretion between control and
      treatment group. At 10 and 100 ng/mL, there was a decrease (P < 0.05) in P4
      concentration, cytochrome P45011A1 (CYP11A1), and 3-beta-hydroxysteroid
      dehydrogenase mRNA expression and localization. There was no difference in mRNA
      expression of steroidogenic acute regulatory protein between control and
      treatment group. In summary, the present study provided evidence that ghrelin and
      its receptor are expressed in bubaline CL and are localized exclusively in the
      cell cytoplasm and ghrelin has an inhibitory effect on P4 production in buffalo. 

PMID- 24906926
TI  - Energy and metabolic sensing G protein-coupled receptors during lactation-induced
      changes in energy balance.
AB  - The free fatty acid receptor FFA1, FFA2, and FFA3 and hydroxy-carboxylic acid
      receptor (HCA2) are G protein-coupled receptors, acting as energy and metabolic
      sensors. Herein, we characterized the tissue-specific mRNA abundance of genes
      encoding for these receptors at different stages of lactation. In addition,
      potential effects of supplementation with or without conjugated linoleic acids
      (CLA) were tested. Tissues from pluriparous cows (subcutaneous adipose tissue
      [SAT] and liver) and from primiparous cows (3 SAT locations, 3 visceral adipose
      tissues, liver, mammary gland, and skeletal muscle) were used from 2 separate
      trials. In primiparous cows, the mRNA abundance of all receptors (FFA3 was not
      detectable by the applied protocol in muscle and udder) was lowest in muscle (P <
      0.05). With the exception of FFA1, gene expression of the investigated receptors
      was higher in adipose tissue than in the non-adipose tissue. Expression of FFA1
      in liver (P < 0.03), FFAR2 in SAT (P < 0.01), and HCA2 in SAT (P < 0.01) from
      pluriparous cows changed during the observation period (days 21 to 252 relative
      to parturition). The correlation between mRNA abundance of HCA2 and peroxisome
      proliferator-activated receptor gamma (PPARG) and likewise PPARG2 (P < 0.01) in
      SAT indicates a link between HCA2 and PPARG. Differences in receptor mRNA
      abundance between the CLA-fed and the control animals were scarce and limited to
      HCA2 and FFA1 in 1 and 2 time points, respectively (less hepatic HCA2mRNA in CLA
      fed pluriparous cows and greater FFA1 mRNA abundance in 2 visceral adipose tissue
      depots in CLA-treated primiparous cows). In view of the metabolic changes
      occurring during the different phases of lactation, in particular, the altered
      concentrations of non-esterified fatty acids and beta-hydroxybutyrate acting as
      receptor ligands, the longitudinal tissue-specific characterization provided
      herein allows for a first insight into the regulation of these receptors at the
      gene expression level. 

PMID- 24906927
TI  - Gonadectomy-related adrenocortical tumors in ferrets demonstrate increased
      expression of androgen and estrogen synthesizing enzymes together with high
      inhibin expression.
AB  - The 2 objectives of this study were to (1) measure by quantitative polymerase
      chain reaction the expression of genes involved in steroid and inhibin synthesis
      in adrenocortical tumors of gonadectomized ferrets and (2) localize by
      immunohistochemistry several proteins that are key to adrenal steroidogenesis.
      Relative to the control adrenals, expression of the messenger RNAs encoding StAR
      (steroidogenic acute regulatory protein; P = 0.039), CYP11A (P = 0.019), CYP21 (P
      = 0.01), and 3beta-HSD (P = 0.004), all involved in the synthesis of
      mineralocorticoids and glucocorticoids, were decreased in the adrenocortical
      tumors. In contrast, expression of cytochrome B5 (CytB5; P = 0.0001) and
      aromatase (P = 0.003), involved in androgen and estrogen synthesis, and both
      inhibin alpha-subunit (P = 0.002) and betaB-subunit (P = 0.001) were upregulated.
      In tumors, immunostaining of CYP21 was low, whereas staining of Cyp17 and CytB5,
      necessary for androgen synthesis, was present. It is concluded that ferret
      adrenocortical tumors express genes for androgen production. In addition, the
      expression of aromatase and inhibin suggests an even more gonadal
      differentiation, which is reminiscent to the fact that both gonads and adrenals
      are derived from a common urogenital primordial cell. 

PMID- 24906928
TI  - Epidermal growth factor receptor is required for estradiol-stimulated bovine
      satellite cell proliferation.
AB  - The objective of this study was to assess the role of the epidermal growth factor
      receptor (EGFR) in estradiol-17beta (E2)-stimulated proliferation of cultured
      bovine satellite cells (BSCs). Treatment of BSC cultures with AG1478 (a specific
      inhibitor of EGFR tyrosine kinase activity) suppresses E2-stimulated BSC
      proliferation (P < 0.05). In addition, E2-stimulated proliferation is completely
      suppressed (P < 0.05) in BSCs in which EGFR expression is silenced by treatment
      with EGFR small interfering RNA (siRNA). These results indicate that EGFR is
      required for E2 to stimulate proliferation in BSC cultures. Both AG1478 treatment
      and EGFR silencing also suppress proliferation stimulated by LR3-IGF-1 (an IGF1
      analogue that binds normally to the insulin-like growth factor receptor (IGFR)-1
      but has little or no affinity for IGF binding proteins) in cultured BSCs (P <
      0.05). Even though EGFR siRNA treatment has no effect on IGFR-1beta mRNA
      expression in cultured BSCs, IGFR-1beta protein level is substantially reduced in
      BSCs treated with EGFR siRNA. These data suggest that EGFR silencing results in
      post-transcriptional modifications that result in decreased IGFR-1beta protein
      levels. Although it is clear that functional EGFR is necessary for E2-stimulated
      proliferation of BSCs, the role of EGFR is not clear. Transactivation of EGFR may
      directly stimulate proliferation, or EGFR may function to maintain the level of
      IGFR-1beta which is necessary for E2-stimulated proliferation. It also is
      possible that the role of EGFR in E2-stimulated BSC proliferation may involve
      both of these mechanisms. 

PMID- 24906929
TI  - Impact of maternal physical activity during gestation on porcine fetal, neonatal,
      and adolescent ovarian development.
AB  - To determine how exercise from mid to late (days 40-104) gestation impacts
      offspring body, uterine and ovarian weight, and ovarian cell proliferation at
      three different developmental stages, Yorkshire gilts were either exercised by
      walking (EX) or not exercised (CON). In parity 1, ovaries and uteri were
      collected from the heaviest (H) and lightest (L) neonates and adolescent (6 mo)
      offspring. In parity 2, mothers were assigned the same treatment groups, and
      ovaries and uteri were collected from H and L fetuses on day 94 of gestation.
      Body weight was greater (P < 0.02) for H than L fetuses and neonates but not
      affected by EX treatment at any developmental stage. Ovarian weight in L but not
      H neonates was greater (P < 0.02) in EX than CON. Labeling index (LI; percentage
      of proliferating cells) was greater (P < 0.01) in cortex than medulla regions of
      fetal and neonatal ovaries. In fetal ovaries, EX enhanced LI (P < 0.01), and LI
      was greater (P < 0.01) in H compared with L offspring. In adolescent ovaries, LI
      was greatest (P < 0.01) in healthy antral and least in atretic antral follicles,
      and LI was greater (P < 0.01) in granulosa than theca cells of healthy antral
      follicles. Thus, exercise increased LI in fetal but not neonatal or adolescent
      ovaries. Although maternal exercise during gestation influences fetal and
      neonatal ovarian development, impacts on fertility remain unknown. 

PMID- 24906930
TI  - Myostatin alters glucose transporter-4 (GLUT4) expression in bovine skeletal
      muscles and myoblasts isolated from double-muscled (DM) and normal-muscled (NM)
      Japanese shorthorn cattle.
AB  - The purpose of this study was to determine whether myostatin alters glucose
      transporter-4 (GLUT4) expression in bovine skeletal muscles and myoblasts
      isolated from double-muscled (DM) and normal-muscled (NM) Japanese Shorthorn
      cattle. Plasma concentrations of glucose were lower in DM cattle than in NM
      cattle (P < 0.01). The expression of GLUT4 messenger RNA (mRNA) in the skeletal
      muscle ex vivo and in myoblasts at 72 h after differentiation in vitro was higher
      in DM cattle than in NM cattle (P < 0.01). In contrast, the NM and DM cattle did
      not differ with respect to skeletal muscle expression of GLUT1 and myocyte
      enhancer factor-2c (MEF2c), a transcription factor of GLUT4. In differentiated
      myoblasts, the expression of GLUT1, GLUT4, and MEF2c mRNAs was greater in DM
      cattle than in NM cattle (P < 0.01). In the presence and absence of insulin,
      glucose uptake in myoblasts was increased in DM cattle relative to that of NM
      cattle (P < 0.01). The addition of myostatin decreased the expression of GLUT4
      and MEF2c mRNAs in DM myoblasts (P < 0.05). Results of the present study suggest
      that myostatin inhibits the expression of GLUT4 mRNA possibly via MEF2c and that
      the greater ability of the DM cattle to produce muscle relative to the NM cattle
      may be due to their greater sensitivity to insulin and greater use of glucose. 

PMID- 24906931
TI  - Influence of season and nutritional status on the direct effects of leptin,
      orexin-A and ghrelin on luteinizing hormone and growth hormone secretion in the
      ovine pituitary explant model.
AB  - The aim of this study was to examine whether leptin (anorexigenic peptide),
      orexin-A, and ghrelin (orexigenic peptides) could directly (ie, independently of
      hypothalamic influences) affect the secretion of luteinizing hormone (LH) and
      growth hormone (GH) by adenohypophyseal (AP) explants obtained from normally fed
      or fasted (48 h) ewes during the breeding and nonbreeding seasons. In addition, a
      specific ovine super leptin antagonist (SLAN-3) was used to assess the
      interactions between leptin and ghrelin and/or orexin-A. Pituitary glands from 16
      ovariectomized Polish Longwool ewes that had received estradiol-releasing
      subcutaneous implants were collected in the breeding (November; n = 8) and
      nonbreeding (May; n = 8) seasons. The AP explants were incubated for 240 min in a
      gas-liquid interface and treated with leptin (50 ng/mL), ghrelin (100 ng/mL),
      orexin-A (100 ng/mL), and SLAN-3 (500 ng/mL) with orexin-A or ghrelin. Treatments
      with leptin and SLAN-3 + orexin-A increased (P < 0.05) LH concentrations in the
      cultures of AP explants from fasted animals in the breeding season. Orexin-A
      increased (P < 0.05) LH secretion by AP explants from both fasted and fed animals
      in the breeding season. Ghrelin stimulated (P < 0.05) GH secretion by AP explants
      collected from fasted animals in nonbreeding season and from normally fed ewes in
      both seasons. Leptin decreased (P < 0.05) GH secretion by AP explants collected
      from fasted ewes in both seasons and from nonfasted ewes in the breeding season.
      However, the treatment with SLAN-3 + ghrelin resulted in greater (P < 0.05) GH
      concentrations compared with leptin treatment of AP explants from fasted ewes in
      the breeding season and from normally fed ewes in nonbreeding season. In summary,
      leptin, orexin-A, and ghrelin exerted direct effects on AP secretory function in
      an ex situ model and both the reproductive season and nutritional status of the
      animals impinged on the direct effects of the peptides on LH and GH release.
      Specifically, orexin-A was more potent than leptin in directly stimulating LH
      secretion in cycling ewes, whereas ghrelin and leptin generally had opposing
      effects on the secretory function of somatotrophs in sheep. 

PMID- 24906932
TI  - Influence of feeding status, time of the day, and season on baseline
      adrenocorticotropic hormone and the response to thyrotropin releasing hormone
      stimulation test in healthy horses.
AB  - Equine pituitary pars intermedia function can be assessed by the measurement of
      baseline and thyrotropin releasing hormone (TRH)-induced concentrations of
      adrenocorticotropic hormone (ACTH); however, these measurements may be affected
      by the environment. Therefore, a prospective observational study evaluated the
      influence of feeding, time of the day, and season on baseline and TRH-induced
      concentrations of ACTH in healthy horses. Baseline ACTH was measured in 50 horses
      before and 2 h after feeding. Six research horses were subjected to a crossover
      study in which 6 TRH tests were performed in 2 different seasons, March-April
      (MA) and July-September (JS), at 2 different times of the day, 8 AM and 8 PM,
      and, under 2 different conditions relative to feeding status, fasted and 2 h
      after feeding. Differences between fasted and fed horses were found in baseline
      ACTH, 17.1 +/- 1.8 versus 46.1 +/- 7.6 pg/mL (P = 0.003) and TRH-stimulated ACTH:
      124.1 +/- 21.3 versus 192.6 +/- 33.1 pg/mL (P = 0.029) at 10 min, and 40.1 +/-
      4.9 versus 73.2 +/- 13.4 pg/mL (P = 0.018) at 30 min post TRH injection. No
      differences were found between tests performed at different times of the day.
      Basal ACTH concentrations were greater in JS than in MA, 17.1 +/- 1.8 versus 11.9
      +/- 0.6 pg/mL (P = 0.006). A seasonal influence was also found in stimulated ACTH
      values, which were much greater in JS 122.7 +/- 36.7 versus 31.2 +/- 7.4 pg/mL,
      at 10 min (P = 0.03) and 39.0 +/- 7.2 versus 19.8 +/- 3.1 pg/mL, at 30 min (P =
      0.03). In addition to season, feeding is a potential confounding factor when
      measuring baseline or stimulated ACTH in horses. In conclusion, feeding status
      should be standardized for the diagnosis of equine pituitary pars intermedia
      dysfunction. 

PMID- 24906933
TI  - Nursing supports neonatal porcine testicular development.
AB  - The lactocrine hypothesis suggests a mechanism whereby milk-borne bioactive
      factors delivered to nursing offspring affect development of neonatal tissues.
      The objective of this study was to assess whether nursing affects testicular
      development in neonatal boars as reflected by: (1) Sertoli cell number and
      proliferation measured by GATA-4 expression and proliferating cell nuclear
      antigen immunostaining patterns; (2) Leydig cell development and steroidogenic
      activity as reflected by insulin-like factor 3 (INSL3), and P450 side chain
      cleavage (scc) enzyme expression; and (3) expression of estrogen receptor-alpha
      (ESR1), vascular endothelial growth factor (VEGF) A, and relaxin family peptide
      receptor (RXFP) 1. At birth, boars were randomly assigned (n = 6-7/group) to
      nurse ad libitum or to be pan fed porcine milk replacer for 48 h. Testes were
      collected from boars at birth, before nursing and from nursed and replacer-fed
      boars at 50 h on postnatal day (PND) 2. Sertoli cell proliferating cell nuclear
      antigen labeling index increased (P < 0.01) from birth to PND 2 in nursed, but
      not in replacer-fed boars. Sertoli cell number and testicular GATA-4 protein
      levels increased (P < 0.01) from PND 0 to PND 2 only in nursed boars. Neither age
      nor nursing affected testicular INSL3, P450scc, ESR1, or VEGFA levels. However,
      testicular relaxin family peptide receptor 1 (RXFP1) levels increased (P < 0.01)
      with age and were greater in replacer-fed boars on PND 2. Results suggest that
      nursing supports neonatal porcine testicular development and provide additional
      evidence for the importance of lactocrine signaling in pigs. 

PMID- 24906934
TI  - Two or 24 h of daily contact with sexually active males results in different
      profiles of LH secretion that both lead to ovulation in anestrous goats.
AB  - Two experiments were conducted to (a) determine whether sexually active males are
      able to stimulate the sexual activity of anestrous female goats when duration of
      contact is reduced to an intermittent contact shorter than 4 daily hours and (b)
      compare the pattern of secretion of LH when anestrous goats are exposed either
      permanently or intermittently to males. In the first experiment, 4 groups of
      anovulatory goats were exposed to sexually active males for 24, 4, 2, or 1 h/d
      during 15 consecutive days, whereas control females remained isolated. More than
      89% of females in the groups exposed to the sexually active bucks ovulated,
      whereas only 5% did so in the control group (P < 0.001). However, the proportion
      of females ovulating before day 4 was greater in the 2-, 4-, or 24-h contact
      groups than in the control, whereas it did not differ between the control group
      and the 1-h contact group (P = 0.02, <0.001, <0.001 and 0.23, respectively). In
      the second experiment, 3 groups of anovulatory goats were exposed permanently (24
      h/d) or intermittently (2 h/d) to bucks during 5 d or remained isolated. We found
      that pulsatility of luteinizing hormone (LH) increased in the intermittent and
      permanent contact groups after males were introduced to females (P = 0.05); this
      pulsatility of LH remained elevated in the permanent-contact group, whereas it
      decreased in the intermittent-contact group, once the male was removed (P = 0.32
      and 0.05, respectively). We conclude that 1 or 2 daily hours of contact with
      sexually active males is sufficient to stimulate ovulatory activity in
      anovulatory goats; however, ovulation is obtained through a different pattern of
      secretion of LH. 

PMID- 24906935
TI  - Isolation of endothelial cells and pericytes from swine corpus luteum.
AB  - From an angiogenesis perspective, the ovary offers a unique opportunity to study
      the physiological development of blood vessels. The first purpose of this work
      was to set up a protocol for the isolation of pig corpus luteum endothelial
      cells, which were characterized by both morphologic parameters and the expression
      of typical molecular markers; we also verified their ability to form capillary
      like structures in a 3-dimensional matrix, their response to hypoxia and their
      migration in the presence of vascular endothelial growth factor (VEGF). The
      effectiveness of our isolation protocol was confirmed by the characteristic
      "cobblestone shape" of isolated cells at confluence as well as their expression
      of all the examined endothelial markers. Our data also showed a significant cell
      production of VEGF and nitric oxide. Isolated endothelial cells were also
      responsive to hypoxia by increasing the expression and production of VEGF and
      decreasing that of nitric oxide. In the angiogenesis bioassay, cells displayed
      the ability of forming capillary-like structures and also exhibited a significant
      migration in the scratch test. Our data suggest that the isolation of luteal
      endothelial cells represents a promising tool in experiments designed to clarify
      the biology of the angiogenic process. Furthermore, we have demonstrated that the
      isolated population comprises a subset of cells with a multidifferentiative
      capacity toward the chondrocytic and adipocytic phenotypes. These data suggest
      the presence of a perivascular or adventitial cell niche in the vascular wall of
      the corpus luteum populated with cells showing mesenchymal stem cell-like
      features, as already demonstrated for the adipose tissue and endometrium. 

PMID- 24906936
TI  - Administration of estradiol benzoate before insemination could skew secondary sex
      ratio toward males in Holstein dairy cows.
AB  - The present study was conducted to investigate the effect of estradiol benzoate
      administration before insemination on secondary sex ratio (proportion of male
      calves at birth) in Holstein dairy cows. Cows (n = 1,647) were randomly assigned
      to 2 experimental groups by parity over a 1-yr period. Cows in the control group
      (n = 827; 232 primiparous and 595 multiparous cows) received 2 administrations of
      PGF2alpha (500 MUg) 14 d apart, started at 30 to 35 d postpartum. Twelve d after
      the second PGF2alpha injection, cows received GnRH (100 MUg), followed by
      administration of PGF2alpha 7 d later. Cows in the treatment group (n = 820; 238
      primiparous and 582 multiparous cows) received the same hormonal administrations
      as the cows in the control group. Additionally, cows in the treatment group
      received estradiol benzoate (1 mg) 1 d after the third PGF2alpha injection.
      Estrus detection by visual observation was started 1 d after the third PGF2alpha
      injection and after estradiol administration in the control (for 6 d) and
      treatment (for 36 h) groups, respectively. Artificial insemination was carried
      out 12 h after observation of standing estrus. Exposure of cows to heat stress at
      conception was determined based on temperature-humidity index. Estrus detection
      rate was lower in primiparous than in multiparous cows (P < 0.05), but conception
      rate was higher in primiparous vs multiparous cows (P < 0.05). Estradiol
      administration improved estrus detection rate and fertility (P < 0.05); moreover,
      it increased secondary sex ratio (adjusted odds ratio: 1.645; P = 0.017).
      Exposure to heat stress diminished heat detection rate and fertility (P < 0.05),
      and altered secondary sex ratio toward males (adjusted odds ratio: 2.863; P =
      0.012). In conclusion, the present study revealed that estradiol administration
      before insemination could improve fertility and increase the probability of
      calves being male in Holstein dairy cows. Moreover, the results showed that cows
      exposed to heat stress around conception had diminished fertility and increased
      secondary sex ratio. 

PMID- 24906937
TI  - Reducing exposure to long days from 75 to 30 days of extra-light treatment does
      not decrease the capacity of male goats to stimulate ovulatory activity in
      seasonally anovulatory females.
AB  - The response of male goats exposed to different durations of long days (LD)
      during an extra-light treatment in autumn-winter, and their ability to induce
      ovulations in seasonally anovulatory goats were investigated in 2 experiments. In
      experiment 1, control males were exposed to natural photoperiod (n = 5), whereas
      4 additional groups (n = 5/group) were exposed to 16 h of light per d during 75,
      45, 30, or 15 d of LD. In the 4 groups, photoperiodic treatments ended on January
      15th. Plasma concentrations of testosterone were determined in blood samples
      obtained once a week from October 15th to May 30th. The rise of testosterone
      levels occurred earlier in males from the 75-LD and 45-LD groups than in those
      from the 30-LD, 15-LD, and control groups (P < 0.05). In addition, the time
      during which levels of testosterone remained >5 ng/mL was longer in males from
      the 75-LD and 45-LD than in those from the 30-LD and 15-LD groups (P < 0.05). In
      experiment 2, a group of anovulatory goats (n = 13) was isolated from males,
      while 3 additional groups were put in contact during 15 d with males previously
      exposed to 75, 45, or 30 days of LD (n = 25, 27, and 26 females/group,
      respectively and n = 3 males per group). The proportion of goats that ovulated
      was higher in the 3 groups in contact with the photo-stimulated males (range: 88%
      92%) than in the group isolated from them (0%; P < 0.05). The proportion of
      pregnant females did not differ between the 3 groups of does in contact with
      photo-stimulated males (range: 78%-92%; P > 0.05). We conclude that, in our
      experimental conditions, a photoperiodic treatment as short as 30 d of LD during
      autumn-winter, stimulated testosterone secretion of bucks during their period of
      sexual rest and rendered them able to induce ovulations in seasonal anestrous
      goats and to obtain pregnancies in these females. 

PMID- 24906938
TI  - Initiation of active immunization against testosterone during early puberty
      alters negative feedback regulation of the hypothalamic-pituitary-testicular axis
      in rabbits.
AB  - To investigate the effects of antitestosterone immunization, initiated during
      early puberty, on hypothalamic-pituitary-testicular feedback in rabbits, 16 early
      pubertal male rabbits were randomly allocated into 2 groups (n = 8), control or
      immunized against testosterone-3(O-carboxymethyl)oxime-BSA in Freund adjuvant at
      4 mo of age (with a booster immunization 4 wk later). Blood samples (for antibody
      titers and hormone concentrations) were collected at 2- or 4-wk intervals after
      immunization. Compared with controls, antitestosterone immunization triggered: a
      substantial and sustained antibody response (P < 0.01); increases in serum
      concentrations of luteinizing hormone (LH) and testosterone and testis weight and
      volume (P < 0.05); hyperplasia of testicular interstitial tissue with clustered
      and hypertrophic Leydig cells; and greater (P < 0.05) enzyme protein and
      messenger RNA (mRNA) expression levels for testicular cholesterol side-chain
      cleavage cytochrome P-450, 17alpha-hydroxylase cytochrome P-450, and 3beta
      dydroxysteroid dehydrogenase. Furthermore, immunoneutralization of testosterone
      upregulated mRNA expressions for genes in sex steroid negative feedback loops,
      including androgen receptor (AR), estrogen receptor alpha (ER-alpha), kisspeptin
      encoded gene (kiss-1) and kisspeptin receptor (G-coupled receptor 54) and
      gonadotropin-releasing hormone (GnRH) in the hypothalamic arcuate nucleus, GnRH
      receptor and LH-beta in pituitary, and AR, inhibin-alpha and betaA subunits in
      testes (P < 0.05). However, immunization did not affect mRNA expressions for
      follicle-stimulating hormone beta, AR, and ER-alpha in pituitary, or ER-alpha in
      testes. We concluded that antitestosterone immunization in male rabbits,
      initiated during early puberty, increased GnRH mRNA expression, and in turn LH
      synthesis by reducing testicular feedback signaling. Reduction of direct
      steroidal effects on the testis may also have increased testosterone secretion.
      Consequently, there was an accelerated testicular development during puberty and
      enhanced testicular function after puberty, which likely conferred prolonged
      reproductive advantages. 

PMID- 24906939
TI  - Pivotal roles for hormonally regulated expression of the HEP21 gene in the
      reproductive tract of chickens for oviduct development and in ovarian
      carcinogenesis.
AB  - Hen egg protein (HEP21) is a 21-kDa secreted protein and has a single copy of the
      Ly6/uPAR domain. Although HEP21 is expressed primarily in the chicken oviduct,
      its biological function(s) in the reproductive system of chickens is not known.
      Thus, in the present study, we investigated expression patterns of HEP21 with
      respect to hormonal regulation, oviduct development, changes in expression in
      laying hens undergoing induced molting, and in the development of ovarian
      carcinogenesis in laying hens. Results of present study indicated that HEP21
      messenger RNA (mRNA) expression increased (P < 0.001) in the chicken oviduct in
      response to estrogen. In situ hybridization analyses revealed expression of HEP21
      mRNA predominantly in glandular (GE) and luminal epithelia of the magnum of the
      chicken oviduct in response to estrogen. The expression of HEP21 mRNA decreased
      (P < 0.001) as the oviduct regressed during induced molting and increased (P <
      0.001) with recrudescence of the oviduct following molting. HEP21 mRNA was most
      abundant in GE of the oviduct during recrudescence, but not during oviduct
      regression following induced molting. Moreover, we found abundant expression of
      HEP21 in GE of cancerous ovaries, but not in normal ovaries of hens.
      Collectively, results of present study suggest that HEP21 is an estrogen
      responsive gene in the oviduct of hens that likely regulates development of the
      chicken oviduct, and egg production and formation. Furthermore, there is
      increased expression of HEP21 in epithelial-derived ovarian cancer suggesting
      that HEP21 could be used for diagnosis and monitoring carcinogenesis in laying
      hens and in women. 

PMID- 24906940
TI  - A novel monoclonal antibody-based enzyme-linked immunosorbent assay to determine
      luteinizing hormone in bovine plasma.
AB  - The development of a novel enzyme-linked immunosorbent assay (ELISA) for
      determining luteinizing hormone (LH) in bovine plasma is described. Anti-bovine
      LH (bLH) monoclonal antibodies (mAbs) were produced and characterized. One mAb
      recognizing the bLH beta subunit was used for immunoaffinity purification of
      substantial amounts of biologically active bLH from pituitary glands. The
      purified bLH in combination with 2 anti-bLH beta subunit mAbs was used to develop
      a sandwich ELISA, which satisfied all the criteria required to investigate LH
      secretory patterns in the bovine species. The ELISA standard curve was linear
      over the range 0.05 to 2.5 ng/mL, and the assay proved suitable for measuring bLH
      in plasma without any prior treatment of samples. Cross-reactivity and recovery
      tests confirmed the specificity of the method. The intra- and inter-assay
      coefficients of variation ranged between 3.41% and 9.40%, and 9.29% and 15.84%,
      respectively. The analytical specificity of the method was validated in vivo by
      provocative tests for LH in heifers, using the LH releasing peptide gonadotropin
      releasing hormone. In conclusion, the adoption of mAbs for this ELISA for coating
      the wells and labeling, combined with the easy one-step production of reference
      bLH, ensures long-term continuity in large-scale measurements of LH in the bovine
      species. 

PMID- 24906941
TI  - The Intego database: background, methods and basic results of a Flemish general
      practice-based continuous morbidity registration project.
AB  - BACKGROUND: Intego is the only operational computerized morbidity registration
      network in Belgium based on general practice data. Intego collects data from over
      90 general practitioners. All the information is routinely collected in the
      electronic health record during daily practice. METHODS: In this article we
      describe the design and methods used within the Intego network together with some
      of its basic results. The collected data, the quality control procedures, the
      ethical-legal aspects and the statistical procedures are discussed. RESULTS:
      Intego contains longitudinal information on 285 357 different patients,
      corresponding to over 2.3% of the Flemish population representative in terms of
      age and sex. More than 3 million diagnoses, 12 million drug prescriptions and 29
      million laboratory tests have been recorded. CONCLUSIONS: Intego enables us to
      present and compare data on health parameters, incidence and prevalence rates,
      laboratory results, and prescribed drugs for all relevant subgroups on a routine
      basis and is unique in Belgium.

PMID- 24906942
TI  - Ameloblastic carcinoma developing in preexisting ameloblastoma with a mutation of
      the p53 gene: a case report.
AB  - OBJECTIVE: Ameloblastic carcinoma is a rare malignant odontogenic tumor. Here we
      present a case of a large ameloblastic carcinoma, which developed in a
      preexisting ameloblastoma in the right submandibular region. STUDY DESIGN: The
      patient was an 84-year-old woman who had received several surgical procedures for
      ameloblastoma, including a segmental mandibulectomy. The dimensions of the tumor
      were 12 * 8 * 5 cm, and both benign ameloblastoma and ameloblastic carcinoma were
      observed histologically. Based on histologic diagnosis, immunohistochemical
      staining and sequence analysis for p53 were performed. RESULTS: Overexpression of
      p53 was observed only in the ameloblastic carcinoma. Additionally, a mutation of
      the p53 gene (TP53) in exon 5 was found by sequence analysis in the ameloblastic
      carcinoma. CONCLUSIONS: This is the first case of ameloblastic carcinoma with a
      mutation of the p53 gene that has been associated with carcinomatous
      transformation.

PMID- 24906943
TI  - Assessment of the fixation of mandibular symphysis fractures using conical
      cannulated screws: mechanical and photoelastic tests.
AB  - OBJECTIVE: The aim of this study was to use mechanical and photoelastic tests to
      compare the performance of cannulated screws with other fixation methods in
      mandibular symphysis fractures. STUDY DESIGN: Ten polyurethane mandibles were
      allocated to each group and fixed as follows: group PRP, 2 perpendicular
      miniplates; group PLL, 1 miniplate and 1 plate, parallel; and group CS, 2
      cannulated screws. Vertical linear loading tests were performed. The differences
      between mean values were analyzed with the Tukey test. The photoelastic test was
      carried out using a polariscope. RESULTS: The results revealed differences
      between the CS and PRP groups at 1, 3, 5, and 10 millimeters of displacement. The
      photoelastic test confirmed higher stress concentration in all groups close to
      the mandibular base, whereas the CS group showed it throughout the region
      assessed. CONCLUSIONS: Conical cannulated screws performed well in mechanical and
      photoelastic tests.

PMID- 24906944
TI  - Clinicopathologic correlation: a mixed radio-opaque and radiolucent lesion of the
      posterior maxilla.

PMID- 24906945
TI  - Bisphosphonate therapy and ankylosis of the temporomandibular joint: is there a
      relationship? A case report.
AB  - Bisphosphonates are an effective class of drugs used for various pathologies of
      bone tissues such as osteoporosis and solid malignant metastatic disease.
      Although reports on adverse events such as bisphosphonate-induced osteonecrosis
      of the jaw are common, ankylosis of the temporomandibular joint in an older
      patient that is possibly associated with bisphosphonate treatment has not, to our
      knowledge, been previously reported. The patient, a 70-year-old woman with none
      of the usual causes for ankylosis, presented with bilateral ankylosis to the
      temporomandibular joints on a background of bisphosphonate treatment. No obvious
      etiologic factor for the bilateral ankylosis was found; thus, this might
      represent another complication of bisphosphonate therapy that dentists and
      physicians need to be aware of. The approach to management of the ankylosis is
      described. 

PMID- 24906946
TI  - Tumor thickness as a predictive factor of lymph node metastasis and disease
      recurrence in T1N0 and T2N0 squamous cell carcinoma of the oral tongue.
AB  - OBJECTIVE: The aim of the study was to compare the thickness of primary tumors
      with the frequency of nodal metastases and survival in patients surgically
      treated for T1/T2N0 oral tongue squamous cell carcinoma. STUDY DESIGN: This is a
      retrospective longitudinal study with 74 patients. RESULTS: None of the patients
      with a tumor thickness (TT) <= 7 mm presented with nodal metastasis, whereas 25
      of the patients with a TT > 7 mm (51.0%) developed metastases (P < .0001).
      Multivariate analysis showed that TT > 7 mm was a risk factor for occult nodal
      metastasis (odds ratio = 8.7; P = .002) with 81.9% accuracy. TT > 10 mm was also
      a predictive factor of worse disease-free survival in these patients (hazard
      ratio = 12.2; P = .003). CONCLUSIONS: Tumor thickness of greater than 7 mm is
      predictive of a higher incidence of lymph node metastasis, and a TT > 10 mm is
      predictive of worse disease-free survival in squamous cell carcinoma of the oral
      tongue.

PMID- 24906947
TI  - Monitoring of the microbiota profile in nukadoko, a naturally fermented rice bran
      bed for pickling vegetables.
AB  - Nukadoko is a fermented rice bran mash traditionally used for pickling vegetables
      in Japan. To date, the production of both homemade and commercial nukadoko
      depends on natural fermentation without using starter cultures. Here, we
      monitored chemical and microbiological changes in the initial batch fermentation
      of nukadoko. Nukadoko samples were prepared by spontaneous fermentation of four
      different brands of rice bran, and microbiome dynamics were analyzed for 2
      months. In the first week, non-Lactobacillales lactic acid bacteria (LAB)
      species, which differed among the samples, grew proportionally to pH decrease and
      lactate increase. Thereafter, Lactobacillus plantarum started growing and
      consumed residual sugars, causing further lactate increase in nukadoko. Finally,
      microbial communities in all tested nukadoko samples were dominated by L.
      plantarum. Taken together, our results suggest that the mixture of the fast
      growing LAB species and slow-growing L. plantarum may be used as a suitable
      starter culture to promote the initial fermentation of nukadoko. 

PMID- 24906948
TI  - Novel compound heterozygous PIGT mutations caused multiple congenital anomalies
      hypotonia-seizures syndrome 3.
AB  - Recessive mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor
      synthesis pathway have been demonstrated as causative of GPI deficiency disorders
      associated with intellectual disability, seizures, and diverse congenital
      anomalies. We performed whole exome sequencing in a patient with progressive
      encephalopathies and multiple dysmorphism with hypophosphatasia and identified
      novel compound heterozygous mutations, c.250G>T (p. Glu84*) and c.1342C>T (p.
      Arg488Trp), in PIGT encoding a subunit of the GPI transamidase complex. The
      surface expression of GPI-anchored proteins (GPI-APs) on patient granulocytes was
      lower than that of healthy controls. Transfection of the Arg488Trp mutant PIGT
      construct, but not the Glu84* mutant, into PIGT-deficient cells partially
      restored the expression of GPI-APs DAF and CD59. These results indicate that PIGT
      mutations caused neurological impairment and multiple congenital anomalies in
      this patient.

PMID- 24906949
TI  - Influence of TCF7L2 gene variants on the therapeutic response to the
      dipeptidylpeptidase-4 inhibitor linagliptin.
AB  - AIMS/HYPOTHESIS: Individuals carrying variants of the transcription factor 7-like
      2 gene (TCF7L2) are at increased risk for type 2 diabetes. These metabolic
      genetic risk factors have been linked to diminished pancreatic islet-cell
      responsiveness to incretins, thus pharmacological interventions aimed at
      amplifying endogenous incretin biology may be affected. However, clinical
      evidence from randomised controlled trials so far is lacking. We investigated the
      influence of TCF7L2 risk alleles on the response to treatment with the
      dipeptidylpeptidase-4 (DPP-4) inhibitor linagliptin from four 24 week, phase III,
      placebo-controlled trials. METHODS: Pharmacogenomic samples and clinical data
      were available from 961 patients with type 2 diabetes. Whole-blood DNA samples
      were genotyped for TCF7L2 single-nucleotide polymorphisms in conjunction with
      assessments of 24 week changes in HbA1c. RESULTS: Linagliptin lowered HbA1c
      meaningfully in all three genotypes of rs7903146 (non-risk variant carriers CC [n
      = 356]: -0.82% [-9.0 mmol/mol], p < 0.0001; heterozygous CT [n = 264]: -0.77% [
      8.4 mmol/mol], p < 0.0001; homozygous risk variant carriers TT [n = 73]: -0.57% [
      6.2 mmol/mol], p < 0.0006). No significant treatment differences were seen
      between CC and CT patients, although HbA1c response was reduced in TT compared
      with CC patients (~0.26% [~2.8 mmol/mol], p = 0.0182).
      CONCLUSIONS/INTERPRETATION: Linagliptin significantly improved hyperglycaemia in
      patients with type 2 diabetes both with and without the TCF7L2 gene diabetes risk
      alleles. However, differences in treatment response were observed, indicating
      that diabetes susceptibility genes may be an important contributor to the inter
      individual variability of treatment response.

PMID- 24906950
TI  - ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic
      alpha and beta cells: similar functions but reciprocal effects on secretion.
AB  - Closure of ATP-regulated K(+) channels (K(ATP) channels) plays a central role in
      glucose-stimulated insulin secretion in beta cells. K(ATP) channels are also
      highly expressed in glucagon-producing alpha cells, where their function remains
      unresolved. Under hypoglycaemic conditions, K(ATP) channels are open in alpha
      cells but their activity is low and only ~1% of that in beta cells. Like beta
      cells, alpha cells respond to hyperglycaemia with K(ATP) channel closure,
      membrane depolarisation and stimulation of action potential firing. Yet,
      hyperglycaemia reciprocally regulates glucagon (inhibition) and insulin secretion
      (stimulation). Here we discuss how this conundrum can be resolved and how reduced
      K(ATP) channel activity, via membrane depolarisation, paradoxically reduces alpha
      cell Ca(2+) entry and glucagon exocytosis. Finally, we consider whether the
      glucagon secretory defects associated with diabetes can be attributed to impaired
      K(ATP) channel regulation and discuss the potential for remedial pharmacological
      intervention using sulfonylureas.

PMID- 24906951
TI  - Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune
      diabetes.
AB  - AIMS/HYPOTHESIS: Latent autoimmune diabetes in adults (LADA) is phenotypically a
      hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised
      but does share genetic predisposition with type 1 diabetes. We aimed to improve
      the genetic characterisation of LADA and hypothesised that type 2 diabetes
      associated gene variants also predispose to LADA, and that the associations would
      be strongest in LADA patients with low levels of GAD autoantibodies (GADA).
      METHODS: We assessed 41 type 2 diabetes-associated gene variants in Finnish
      (phase I) and Swedish (phase II) patients with LADA (n = 911) or type 1 diabetes
      (n = 406), all diagnosed after the age of 35 years, as well as in non-diabetic
      control individuals 40 years or older (n = 4,002). RESULTS: Variants in the ZMIZ1
      (rs12571751, p = 4.1 * 10(-5)) and TCF7L2 (rs7903146, p = 5.8 * 10(-4)) loci were
      strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p = 0.0012),
      HHEX (rs1111875, p = 0.0024 in Finns) and MTNR1B (rs10830963, p = 0.0039) loci
      showed the strongest association in patients with low GADA, supporting the
      hypothesis that the disease in these patients is more like type 2 diabetes. In
      contrast, variants in the KLHDC5 (rs10842994, p = 9.5 * 10(-4) in Finns),
      TP53INP1 (rs896854, p = 0.005), CDKAL1 (rs7756992, p = 7.0 * 10(-4); rs7754840, p
      = 8.8 * 10(-4)) and PROX1 (rs340874, p = 0.003) loci showed the strongest
      association in patients with high GADA. For type 1 diabetes, a strong association
      was seen for MTNR1B (rs10830963, p = 3.2 * 10(-6)) and HNF1A (rs2650000, p =
      0.0012). CONCLUSIONS/INTERPRETATION: LADA and adult-onset type 1 diabetes share
      genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form
      of diabetes and distinguishing them from patients with classical young-onset type
      1 diabetes.

PMID- 24906952
TI  - Lipopolysaccharide binding protein, obesity status and incidence of metabolic
      syndrome: a prospective study among middle-aged and older Chinese.
AB  - AIMS/HYPOTHESIS: Although microbiota-derived endotoxaemia has previously been
      shown to induce metabolic disorders, data from population-based longitudinal
      studies are scarce. This study therefore investigated the associations between
      lipopolysaccharide binding protein (LBP) levels and 6 year incident metabolic
      syndrome (MetS), as well as the potentially modifying effects of obesity status
      in middle-aged and older Chinese men and women. METHODS: A total of 2,529 men and
      women aged 50-70 years from Beijing and Shanghai, China, were followed for 6
      years. Those free of MetS at baseline (1,312) were included in the analyses for
      the risk of developing MetS. Baseline plasma LBP was measured using an ELISA kit.
      RESULTS: During the 6 year follow-up, 449 (34.2%) participants developed MetS.
      Baseline LBP was significantly associated with BMI, waist circumference, blood
      lipid profile and C-reactive protein (CRP) both at baseline and during follow-up
      (all p < 0.05). The RR for incident MetS comparing extreme quartiles of LBP was
      1.28 (95% CI 1.04, 1.58), after multivariate adjustment including BMI and CRP. In
      stratified analysis, LBP was positively associated with incident MetS only in
      normal-weight participants (RR, comparing extreme tertiles, 1.59; 95% CI 1.18,
      2.15; p(trend)= 0.002), but not in their overweight/obese counterparts (RR,
      comparing extreme tertiles, 0.99; 95% CI 0.80, 1.22; p(trend) = 0.880). A
      significant interaction was observed between LBP and obesity status
      (p(interaction) = 0.013). CONCLUSIONS/INTERPRETATION: Our study suggested that
      elevated plasma LBP was associated with an increased risk of developing MetS
      among middle-aged and older Chinese, especially in normal-weight individuals.

PMID- 24906953
TI  - Gas sensing in nematodes.
AB  - Nearly all animals are capable of sensing changes in environmental oxygen (O2)
      and carbon dioxide (CO2) levels, which can signal the presence of food,
      pathogens, conspecifics, predators, or hosts. The free-living nematode
      Caenorhabditis elegans is a powerful model system for the study of gas sensing.
      C. elegans detects changes in O2 and CO2 levels and integrates information about
      ambient gas levels with other internal and external cues to generate context
      appropriate behavioral responses. Due to its small nervous system and amenability
      to genetic and genomic analyses, the functional properties of its gas-sensing
      microcircuits can be dissected with single-cell resolution, and signaling
      molecules and natural genetic variations that modulate gas responses can be
      identified. Here, we discuss the neural basis of gas sensing in C. elegans, and
      highlight changes in gas-evoked behaviors in the context of other sensory cues
      and natural genetic variations. We also discuss gas sensing in other free-living
      nematodes and parasitic nematodes, focusing on how gas-sensing behavior has
      evolved to mediate species-specific behavioral requirements. 

PMID- 24906954
TI  - A MicroRNA Profile in Fmr1 Knockout Mice Reveals MicroRNA Expression Alterations
      with Possible Roles in Fragile X Syndrome.
AB  - Fragile X syndrome (FXS), a common form of inherited mental retardation, is
      caused by a loss of expression of the fragile X mental retardation protein
      (FMRP). FMRP is involved in brain functions by interacting with mRNAs and
      microRNAs (miRNAs) that selectively control gene expression at translational
      level. However, little is known about the role of FMRP in regulating miRNA
      expression. Here, we found a development-dependant dynamic expression of Fmr1
      gene (encoding FMRP) in mouse hippocampus with a small peak at postnatal day 7
      (P7). MiRNA microarray analysis showed that the levels of 38 miRNAs showed a
      significant increase with about 15 ~ 250-folds and the levels of 26 miRNAs showed
      a significant decrease with only about 2 ~ 4-folds in the hippocampus of P7 Fmr1
      knockout (KO) mice. The qRT-PCR assay showed that nine of the most increased
      miRNAs (>100-folds in microarrays) increased about 40 ~ 70-folds and their pre
      miRNAs increased about 5 ~ 10-folds, but no significant difference in their pri
      miRNA levels was observed, suggesting that the alterations of partial miRNAs are
      an indirect consequence of FMRP lacking. We further demonstrated that a set of
      protein-coding mRNAs, potentially targeted by the nine miRNAs, were down
      regulated in the hippocampus of Fmr1 KO mice. Finally, luciferase assays
      demonstrated that miR-34b, miR-340, and miR-148a could down-regulate the reporter
      gene expression by interacting with the Met 3' UTR. Taken together, these
      findings suggest that the miRNA expression alterations resulted from the absence
      of FMRP might contribute to molecular pathology of FXS. 

PMID- 24906955
TI  - The utility of circulating LHCGR as a predictor of Down's syndrome in early
      pregnancy.
AB  - BACKGROUND: Previous studies showed that soluble LHCGR/hCG-sLHCGR concentrations
      in serum or plasma combined with PAPP-A and free betahCG significantly increased
      the sensitivity of Down's syndrome screen at early pregnancy without altering the
      false positive rate. The goal of the present study was to further examine the
      role of sLHCGR forms as combinatorial markers and to investigate whether sLHCGR
      could serve as an independent biomarker for Down's syndrome in first trimester
      pregnancy screens. METHODS: The PAPP-A, free betahCG, and hCG-sLHCGR
      concentrations together with nuchal translucency (NT) were measured in 40 Down's
      and 300 control pregnancies. The sLHCGR concentration was analysed in 40 Down's
      and 206 control pregnancies. RESULTS: The hCG-LHCGR in combination with PAPP-A
      and free betahCG increased the detection rate (DR) by 35% without altering the
      false positive rate (FPR). The sLHCGR: hCG-sLHCGR ratio alone detected 80% of
      Down's pregnancies in first trimester screening, with a false positive rate of
      0.5%. CONCLUSIONS: While measurement of sLHCGR forms in combination with PAPP-A
      and free betahCG significantly increases the detection rate of Down's syndrome at
      first trimester, the ratio of sLHCGR: hCG-sLHCGR acts as an independent marker
      with a detection rate that is significantly higher than the existing biochemical
      markers individually for prenatal first trimester screening of Down's syndrome.

PMID- 24906956
TI  - Paediatric orchidopexy: a need for dedicated paediatric surgical training among
      urologists?
AB  - BACKGROUND: Undescended testis (UDT) is one of the most common congenital
      abnormalities with a prevalence of about 1% at the age of 1 year. UDT is
      associated with an increased risk of testicular tumours and infertility. AIMS:
      The aim of this study was to assess who is carrying out paediatric orchidopexy in
      Ireland. METHODS: A survey was distributed via Survey Monkey to all Consultant
      Paediatric Surgeons and Urologists in Ireland. RESULTS: Twenty-seven (64.3%)
      urologists and five (71.4%) paediatric surgeons responded to our online survey.
      Of the urologists, 100% reported formal training in paediatric orchidopexy. Eight
      (29.6%) underwent a dedicated paediatric fellowship. 13 (48.1%) currently perform
      paediatric orchidopexy. Nine (33%) think it should be carried out by a urologist,
      whereas eight (29.6%) think it should be carried out by paediatric surgeon. The
      mean age at which urologists think an orchidopexy for UDT should be performed by
      was 18 months (range 1-4 years). Approximately 400 orchidopexies are performed
      per year by the surveyed urologists. Of the paediatric surgeons, three (60%) feel
      it should be carried out by a paediatric surgeon whereas two (40%) feel it does
      not matter. All paediatric surgeons feel it should be performed by 1 year of age.
      Approximately 700 orchidopexies are performed per year by the surveyed paediatric
      surgeons. CONCLUSION: UDT is a concerning condition which requires intervention
      at an early stage. Dedicated training in core paediatric procedures is required
      to continue to meet this need for the future to prevent delayed orchidopexy and
      resultant increased risk of testicular tumours.

PMID- 24906957
TI  - Induction of latent memory for conditioned food aversion and its transformation
      into "active" state depend on translation and transcription processes.
AB  - Mechanisms of induction and retrieval of latent (hidden) memory for conditioned
      food aversion were investigated in snails. After initial training (single
      combination of a food stimulus with electric shock), aversive reactions to
      presentation of the conditioned food stimulus were not revealed. Repeated
      presentation of the stimuli in 12 days after the first combination was followed
      by the appearance of aversive food reactions that persisted for at least 14 days.
      Injections of inhibitors of protein (cycloheximide) or RNA (alpha-amanitin)
      synthesis immediately after the first or second combined presentation of the
      stimuli disturbed skill performance. We hypothesized that single combination of
      food and reinforcing stimuli led to translation- and transcription-dependent
      induction of latent conditioned food aversion memory. Transformation of this
      memory into an active state after repeated presentation of the stimulus
      combination also depends on the synthesis of new proteins and RNA. 

PMID- 24906958
TI  - Antifibrotic activity of conjugates based on amphiphilic pluronic F68 and
      hydrophobic pluronic L31 with hyaluronate-endo-beta-N-acetylhexosaminidase in
      pulmonary fibrosis.
AB  - Antifibrotic activity of intranasally administered conjugates of pluronics L31
      and F68 with hyaluronate-endo-beta-N-acetylhexosaminidase was studied in C57Bl/6
      mice under conditions of single and repeated bleomycin-induced injury to the
      alveolar epithelium. Conjugates were prepared using the technique of protein
      immobilization with ionizing radiation. We demonstrate that in cases of single
      and repeated injuries to the alveolar epithelium, the conjugates administered
      during phases of inflammation or deposition of fibrotic masses prevent the
      development of pulmonary fibrosis. The conjugates demonstrated more pronounced
      antifibrotic activity than hyaluronate-endo-beta-N-acetylhexosaminidase. The
      conjugate based on hydrophobic pluronic L31 showed higher effectiveness in
      comparison with the conjugate based on amphiphilic pluronic F68. 

PMID- 24906959
TI  - Dynamics of locomotor activity and heat production in rats after acute stress.
AB  - The dynamics of locomotor activity and heat production were studied in rats
      demonstrating passive and active behavior in the open field test at different
      time after exposure to acute emotional stress caused by 12-h immobilization
      during dark hours. The most pronounced changes in behavior and heat production
      followed by disturbances in circadian rhythms of these parameters were detected
      within the first 2 days after stress. In contrast to behaviorally active rats,
      the most significant decrease in locomotor activity and heat production of
      passive animals subjected to emotional stress was observed during dark hours.
      Circadian rhythms of behavior and heat production in rats tended to recover on
      day 3 after immobilization stress. These data illustrate the specificity of
      metabolic and behavioral changes reflecting the shift of endogenous biological
      rhythms in individuals with different prognostic resistance to stress at
      different terms after exposure to negative emotiogenic stimuli.

PMID- 24906960
TI  - Combined blockade of NMDA and AMPA receptors prevents acute kainate seizures and
      chronic kainate lethality in rats.
AB  - Single intramuscular injection of selective of NMDA receptor blocker memantine in
      the maximum dose of 20 mg/kg prevented the development of acute generalized tonic
      clonic kainate seizures in 60% rats, but did not alleviate clonic kainate
      seizures and prevented chronic kainate lethality in only 30% rats. Intramuscular
      injection of NBQX, a selective blocker of AMPA receptors (10 mg/kg), produced
      more pronounced anticonvulsant and neuroprotective effects: it prevented
      generalized kainate seizures and chronic kainate lethality in 100 and 80% rats,
      respectively. However, even the high dose of NBQX prevented the clonic kainate
      seizures only in 30% rats. The intramuscular injection of novel agent IEM-2121
      (0.03-1.00 mg/kg) known to block both AMPA and NMDA receptors, prevented the
      clonic kainate seizures only in 50-70%, although it precluded the chronic kainate
      lethality in 100%. 

PMID- 24906961
TI  - Urokinase stimulates production of matrix metalloproteinase-9 in fibroblasts with
      involvement of reactive oxygen species.
AB  - In cultured fibroblasts, urokinase stimulated expression of MMP-9 and generation
      of ROS, while antioxidant ebselen abolished the stimulating effect of urokinase
      on MMP-9 expression. sTNF-alpha produced similar and more pronounced stimulating
      effect. The data showed that urokinase could regulate MMP-9 expression via ROS
      generation in fibroblasts, which can play an important role in stimulation of
      their migration and development of constrictor (negative) vascular remodeling due
      to thickening of the adventitia. 

PMID- 24906962
TI  - Role of nitric oxide in development of centralization of blood circulation upon
      experimental hemorrhagic shock.
AB  - Effects of a NO donor L-arginine and a non-selective NO-synthase inhibitor N(G)
      nitro-Larginine methyl ester on BP, microcirculation, acid-base balance, and gas
      content of blood were examined on rat model of hemorrhagic shock; the substances
      were administered without infusion media before blood loss. Bloodletting was
      stopped after manifestation of marked microcirculation disorders. Inhibition of
      NO synthesis in response to blood loss resulted in pronounced centralization of
      blood circulation with microcirculation disturbances, which was accompanied by
      metabolic changes aggravating hemorrhagic shock. Administration of NO donor
      reduced the degree of circulation centralization, maintained vasodilatatory
      vascular tone and perfusion of vital organs, improved animal resistance to blood
      loss, and prolonged their lifespan. Enhanced NO generation after administration
      of NO donor promoted longer microcirculation maintenance, which suggests that the
      so-called basal level of NO is essential at early stages of hemorrhagic shock. 

PMID- 24906963
TI  - The relationship between parental catastrophizing about child pain and distress
      in response to medical procedures in the context of childhood cancer treatment: a
      longitudinal analysis.
AB  - OBJECTIVE: Children with leukemia frequently undergo invasive medical procedures,
      such as lumbar punctures (LPs) and bone marrow aspirations (BMAs). To date, cross
      sectional evidence indicates that LP/BMA procedures continue to elicit distress
      over the course of treatment in children and parents. METHOD: The current study
      used prospective analyses investigating in 28 children diagnosed with leukemia,
      the course of parental and child distress when confronted with consecutive LP/BMA
      procedures and potential moderation by catastrophic thinking. Parents' level of
      catastrophic thoughts was assessed before the first treatment-related LP/BMA,
      while child and parent distress was reported on after each LP/BMA procedure.
      RESULTS: Whereas parental distress decreased over time among low catastrophizing
      parents, LP/BMA procedures remained highly distressing for high catastrophizing
      parents. Child distress during LP/BMA procedures increased over time and was
      positively related with parental distress. CONCLUSION: These findings stress the
      importance of targeting child and parent distress as early as possible in
      treatment.

PMID- 24906964
TI  - Factors affecting motivation and retention of primary health care workers in
      three disparate regions in Kenya.
AB  - BACKGROUND: The World Health Organization (WHO) and the Government of Kenya alike
      identify a well-performing health workforce as key to attaining better health.
      Nevertheless, the motivation and retention of health care workers (HCWs) persist
      as challenges. This study investigated factors influencing motivation and
      retention of HCWs at primary health care facilities in three different settings
      in Kenya - the remote area of Turkana, the relatively accessible region of
      Machakos, and the disadvantaged informal urban settlement of Kibera in Nairobi.
      METHODS: A cross-sectional cluster sample design was used to select 59 health
      facilities that yielded interviews with 404 health care workers, grouped into 10
      different types of service providers. Data were collected in November 2011 using
      structured questionnaires and a Focus Group Discussion guide. Findings were
      analyzed using bivariate and multivariate methods of the associations and
      determinants of health worker motivation and retention. RESULTS: The levels of
      education and gender factors were lowest in Turkana with female HCWs representing
      only 30% of the workers against a national average of 53%. A smaller proportion
      of HCWs in Turkana feel that they have adequate training for their jobs. Overall,
      13% of the HCWs indicated that they had changed their job in the last 12 months
      and 20% indicated that they could leave their current job within the next two
      years. In terms of work environment, inadequate access to electricity, equipment,
      transport, housing, and the physical state of the health facility were cited as
      most critical, particularly in Turkana. The working environment is rated as
      better in private facilities. Adequate training, job security, salary, supervisor
      support, and manageable workload were identified as critical satisfaction
      factors. Family health care, salary, and terminal benefits were rated as
      important compensatory factors. CONCLUSIONS: There are distinct motivational and
      retention factors that affect HCWs in the three regions. Findings and policy
      implications from this study point to a set of recommendations to be implemented
      at national and county levels. These include gender mainstreaming, development of
      appropriate retention schemes, competitive compensation packages, strategies for
      career growth, establishment of a model HRH community, and the conduct of a
      discrete choice experiment.

PMID- 24906965
TI  - Clinical presentation of early-onset Alzheimer's disease as a result of mutation
      in exon 12 of the PSEN-1 gene.
AB  - INTRODUCTION: Mutations in the gene for presenilin 1 (PSEN-1) cause familial,
      early-onset Alzheimer's disease (EOAD). Diagnosis of EOAD is often a challenge
      because of the high frequency of atypical presentations. Clinical manifestation
      of EOAD may vary depending on underlying mutation; specific genetic mutations
      influence development of specific clinical phenotypes; however, intrafamilial
      phenotypic heterogeneity has also been noted in some pedigrees. CASE
      PRESENTATION: We report a case of a 36-year-old woman presenting with progressive
      behavioral disturbances, dementia, involuntary movements, pyramidal signs,
      epilepsy, and a family history of early-onset dementia accompanied by involuntary
      movements. On genetic testing, the mutation at codon 424 (Leu->Arg) in PSEN-1
      gene was identified. CONCLUSION: Our case describes a new phenotype of a known
      mutation of PSEN-1 at codon 424.

PMID- 24906966
TI  - Apolipoprotein E Allele and Hearing Thresholds in Older Adults.
AB  - BACKGROUND: Whether apolipoprotein E (APOE) E4 allele status which is associated
      with an increased risk of cognitive decline is also associated with hearing
      impairment is unknown. METHODS: We studied 1833 men and women enrolled in the
      Health, Aging and Body Composition study. Regression models adjusted for
      demographic and cardiovascular risk factors were used to assess the cross
      sectional association of APOE-E4 status with individual pure tone hearing
      thresholds and the 4-frequency pure tone average (0.5-4 kHz) in the better
      hearing ear. RESULTS: Compared to participants with no APOE-E4 alleles,
      participants with 1 allele had better thresholds at 4.0 kHz (beta = -2.72 dB, P =
      .013) and 8.0 kHz (beta = -3.05 kHz, P = .006), and participants with 2 alleles
      had better hearing thresholds at 1.0 kHz (beta = -8.56 dB, P = .021). CONCLUSION:
      Our results suggest that APOE-E4 allele status may be marginally associated with
      better hearing thresholds in older adults.

PMID- 24906967
TI  - Potential Similarities in Temporal Lobe Epilepsy and Alzheimer's Disease: From
      Clinic to Pathology.
AB  - Alzheimer's disease (AD) is clinically characterized by insidious onset of memory
      and cognitive impairments, which are also presented in patients with temporal
      lobe epilepsy (TLE). Many studies have shown that seizures occur in some patients
      with AD, and AD is a risk factor for epilepsy, mainly complex partial and
      secondary generalized seizure. Here, we focus on the relationship between TLE and
      AD in clinical and pathological aspects, as they are having similar comorbidities
      and mechanisms. In this study, we first reviewed the clinical observations that
      showed concomitant AD and TLE. Then, we picked up common genetic and pathological
      changes in both the diseases from neurobiological researches. Although both the
      diseases have delicate differences in many aspects, their common characteristics
      intrigue more detailed research to be done by newer technology.

PMID- 24906968
TI  - Acupuncture stimulation of Taichong (Liv3) and Hegu (LI4) modulates the default
      mode network activity in Alzheimer's disease.
AB  - OBJECTIVES: The acupuncture has been used in the therapy of Alzheimer disease
      (AD), however, its neural underpins are still unclear. The aim of this study is
      to examine the acupuncture effect on the default mode network (DMN) in AD by
      using resting state functional magnetic resonance imaging (RS-fMRI). METHODS:
      Twenty-eight subjects (14 AD and 14 normal controls (NC)) participated in this
      study. RS-fMRI data were acquired before and after acupuncture, while during the
      acupuncture, the procession of acupuncture stimulation on the acupoints of Tai
      chong (Liv3) and Hegu (LI4) lasted for 3 minutes. RESULTS: Region of interest
      analysis showed that the impaired DMN connectivity in AD (identified by comparing
      the pre-acupuncture RS-fMRI of AD and NC), specifically the left cingulate gyrus
      (CG) and right inferior parietal lobule (IPL), were significantly changed for the
      better. The whole-brain exploratory analysis further demonstrated these results
      and found some new regions respond to the acupuncture effect on AD, with a
      cluster in the left posterior cingulate cortex (PCC), the right middle temporal
      gyrus (MTG) together with right IPL showed increased within-DMN connectivity; and
      the bilateral CG and left PCu showed decreased within-DMN connectivity. Moreover,
      the acupuncture effect on the right MTG was significantly correlated with disease
      severity as measured by Mini-Mental State Examination (MMSE) and Montreal
      Cognitive Assessment (MoCA) scores. CONCLUSION: It was found that the acupuncture
      stimulation could modulate the DMN activity in AD. The current findings suggest
      that the acupuncture treatment on the relative earlier AD patients might have a
      better therapy effect.

PMID- 24906969
TI  - A selective egocentric topographical working memory deficit in the early stages
      of Alzheimer's disease: a preliminary study.
AB  - The aim of this study was to determine whether an egocentric topographical
      working memory (WM) deficit is present in the early stages of Alzheimer's disease
      (AD) with respect to other forms of visuospatial WM. Further, we would
      investigate whether this deficit could be present in patients having AD without
      topographical disorientation (TD) signs in everyday life assessed through an
      informal interview to caregivers. Seven patients with AD and 20 healthy
      participants performed the Walking Corsi Test and the Corsi Block-Tapping Test.
      The former test requires memorizing a sequence of places by following a path and
      the latter is a well-known visuospatial memory task. Patients with AD also
      performed a verbal WM test to exclude the presence of general WM impairments.
      Preliminary results suggest that egocentric topographical WM is selectively
      impaired, with respect to visuospatial and verbal WM, even without TD suggesting
      an important role of this memory in the early stages of AD.

PMID- 24906970
TI  - Occurrence of norovirus and hepatitis A virus in wild mussels collected from the
      Baltic Sea.
AB  - The aim of the study was to define the occurrence of human noroviruses of
      genogroup I and II (NoV GI and NoV GII) and hepatitis A virus (HAV) in the Baltic
      Sea mussels. The shellfish samples were taken at the sampling sites located on
      the Polish coast. In total, 120 shellfish were tested as pooled samples using RT
      PCR and hybridisation with virus specific probes. NoV GI was detected in 22
      (18.3%), NoV GII in 28 (23.3%), and HAV in 9 (7.5%) of the shellfish. The
      nucleotide sequence analysis of the detected NoV GII strains showed a 97.3-99.3%
      similarity to GII.4 virus strain. This is the first report describing the NoV and
      HAV occurrence in wild Baltic mussels and their possible role as bioindicators of
      seawater contamination with human enteric viruses.

PMID- 24906971
TI  - Measuring progress in neglected disease drug development.
AB  - BACKGROUND: Since the late 1990s, funding for development of neglected disease
      drugs has increased with an influx of resources from product development
      partnerships (PDPs). Previous research showed modest gains in drug approvals and
      products in Phase III of clinical development in the period 2000-2008. OBJECTIVE:
      We assessed the 2009-2013 period in terms of numbers of products in Phase III
      development and numbers of approvals. Subsequently, we calculated the PDP share
      in terms of sponsorship of new approvals. We also identified the numbers of 2000
      2013 approvals included in the World Health Organization's Essential Drug List
      (EDL). METHODS: We identified new approvals and Phase III products targeting
      neglected diseases in the period 2009-2013 by searching ClinicalTrials.gov, IMS
      R&D Focus, and Investigational Drugs Database, as well as drug regulatory agency
      websites. Subsequently, we determined which products approved between 2000 and
      2013 have been included in the most recent version of the EDL. RESULTS: We found
      20 new approvals targeting neglected diseases in the period 2009-2013. PDPs were
      the primary sponsor of 57% of new approvals in this time frame. Approvals
      included 1 new molecular entity, 5 vaccines, 2 new indications, 9 fixed-dose
      combinations, and 3 new formulations. HIV/AIDS (pediatric indications) and
      malaria accounted for 60% of approvals in 2009-2013. The average number of new
      approvals per year for neglected diseases rose from 2.6 in 2000-2008 to 4.9 in
      2009-2013. The World Health Organization included 44% of 2000-2013 approved
      products on the EDL. We found 18 products currently in Phase III of clinical
      development. Products in Phase III testing included 3 new molecular entities, 6
      vaccines, 2 fixed-dose combinations, 5 new indications, and 2 new formulations.
      CONCLUSIONS: Increased funding through PDPs for neglected disease drug
      development seems to be producing results. Approvals and products in Phase III
      testing have shown a steady increase since 2000, with nearly a doubling of
      products in 2009-2013, compared with 2000-2008, in terms of the annual average
      yield. However, only 3 new molecular entities have been approved in 14 years. In
      addition, malaria and HIV (pediatric indications) seem to have benefited most
      from increased funding, whereas less success has occurred with other diseases.
      Inclusion of newly approved products on the EDL has been slow and limited, with
      only 44% of new approvals added to the list. Uneven progress suggests funding
      could be better targeted. In addition, PDPs could do more to facilitate access,
      in particular by working closely with the World Health Organization to assess the
      clinical effectiveness and cost-effectiveness of new approvals.

PMID- 24906972
TI  - Central nervous system regeneration.

PMID- 24906973
TI  - Evaluation of an integrated care program for schizophrenia: concept and study
      design.
AB  - Concept and design of an independent scientific evaluation of different pathways
      of care for schizophrenia patients in Germany with respect to effectiveness and
      efficiency are presented. In this prospective, observational study, schizophrenia
      patients receiving an integrated care treatment, the intervention group (IG), are
      compared with patients under routine care conditions treated by the same
      physician (first control group, CG 1). A second control group (CG 2) of patients
      treated by office-based psychiatrists not participating in the integrated care
      program will be recruited and their data compared with the two other groups. The
      total amount of psychiatric hospital days after 12 months is defined as primary
      outcome parameter. Secondary outcome parameters comprise the frequency of
      psychiatric inpatient readmissions, severity of schizophrenia symptoms, remission
      rates and quality of life. Patients undergo assessments at baseline, month 6 and
      12 using standardized and experimental questionnaires. Routine data of a regional
      German social health insurance fund complement information on included patients.
      Additionally, a cost-effectiveness and cost-utility analysis will be performed.
      Until now, 137 psychiatrists included 980 patients in the integrated care project
      in Lower Saxony, Germany, and 47 psychiatrists (IG and both CGs) are willing to
      participate in the independent evaluation. For the first time, a prospective
      observational controlled evaluation study of a countrywide integrated care
      project planning to recruit 500 schizophrenia patients has started using
      comprehensive assessments as well as routine data of a social health insurance
      fund.

PMID- 24906974
TI  - Commensal bacteria drive endogenous transformation and tumour stem cell marker
      expression through a bystander effect.
AB  - OBJECTIVE: Commensal bacteria and innate immunity play a major role in the
      development of colorectal cancer (CRC). We propose that selected commensals
      polarise colon macrophages to produce endogenous mutagens that initiate
      chromosomal instability (CIN), lead to expression of progenitor and tumour stem
      cell markers, and drive CRC through a bystander effect. DESIGN: Primary murine
      colon epithelial cells were repetitively exposed to Enterococcus faecalis
      infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)-an endogenous
      mutagen and spindle poison produced by macrophages. CIN, gene expression, growth
      as allografts in immunodeficient mice were examined for clones and expression of
      markers confirmed using interleukin (IL) 10 knockout mice colonised by E.
      faecalis. RESULTS: Primary colon epithelial cells exposed to polarised
      macrophages or 4-hydroxy-2-nonenal developed CIN and were transformed after 10
      weekly treatments. In immunodeficient mice, 8 of 25 transformed clones grew as
      poorly differentiated carcinomas with 3 tumours invading skin and/or muscle. All
      tumours stained for cytokeratins confirming their epithelial cell origin. Gene
      expression profiling of clones showed alterations in 3 to 7 cancer driver genes
      per clone. Clones also strongly expressed stem/progenitor cell markers Ly6A and
      Ly6E. Although not differentially expressed in clones, murine allografts
      positively stained for the tumour stem cell marker doublecortin-like kinase 1.
      Doublecortin-like kinase 1 and Ly6A/E were expressed by epithelial cells in colon
      biopsies for areas of inflamed and dysplastic tissue from E. faecalis-colonised
      IL-10 knockout mice. CONCLUSIONS: These results validate a novel mechanism for
      CRC that involves endogenous CIN and cellular transformation arising through a
      microbiome-driven bystander effect.

PMID- 24906975
TI  - Relationship between glucose metabolism and non-alcoholic fatty liver disease
      severity in morbidly obese women.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an independent predictor
      of type 2 diabetes mellitus (T2DM). Insulin resistance and beta-cell dysfunction
      are involved in the pathogenesis of T2DM. Insulin resistance is associated with
      NAFLD but little is known about beta-cell dysfunction and NAFLD. AIM: We tested
      whether NAFLD severity is associated with insulin sensitivity and beta-cell
      function in morbidly obese women. SUBJECTS AND METHODS: We studied 61 Caucasian
      women aged 18-60 years without T2DM and with a body mass index ranging from 35.3
      to 48.8 kg/m2. The insulin sensitivity index (ISI) and the disposition index (DI)
      from oral glucose tolerance testing were used as measures of insulin sensitivity
      and beta-cell function, respectively. Fat was measured by dual-energy X-ray
      absorptiometry. Fatty liver was diagnosed by ultrasonography and ordinally coded
      as 0 = none, 1 = light, 2 = moderate, 3 = severe. Proportional-odds logistic
      regression was used to evaluate the association of NAFLD severity with log(e)ISI
      and log(e)DI with and without correction for total and truncal fat. RESULTS: The
      odds of more severe vs. less severe NAFLD decreased for increasing log(e)ISI
      [odds ratio (OR) 0.40, 95 % CI 0.19-0.84, p < 0.05] and log(e)DI (OR 0.80, 95 %
      CI 0.69-0.92, p < 0.01). Neither total nor truncal fat had any effect on these
      associations. CONCLUSION: In morbidly obese women, NAFLD severity is inversely
      associated with insulin sensitivity and beta-cell function. The association of
      NAFLD severity with beta-cell dysfunction is stronger than that with insulin
      resistance.

PMID- 24906977
TI  - Endocrinology and art. Leonardo da Vinci "design of Lady with Graves' disease"
      (1452-1519).

PMID- 24906976
TI  - Adiponectin, interleukin-6, monocyte chemoattractant protein-1, and regional fat
      mass during 12-month randomized treatment with metformin and/or oral
      contraceptives in polycystic ovary syndrome.
AB  - CONTEXT: Central obesity in polycystic ovary syndrome (PCOS) is associated with
      increased inflammatory markers and increased risk for type 2 diabetes. OBJECTIVE:
      To evaluate if improved body composition during treatment with metformin (M) vs.
      oral contraceptive pills (OCP) was associated with changes in circulating
      adiponectin, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1.
      PATIENTS AND INTERVENTIONS: Ninety patients with PCOS were randomized to 12-month
      treatment with M (2 g/day), M + OCP (150 mg desogestrel + 30 microgram
      ethinylestradiol) or OCP. Adiponectin, IL-6, MCP-1, whole body DXA scans, and
      clinical evaluations were performed before and after the intervention period in
      the 65 study completers. MAIN OUTCOME MEASURES: Changes in inflammatory markers
      and changes in total and regional fat mass estimates. RESULTS: Adiponectin, IL-6,
      and MCP-1 levels were unchanged during the three types of medical intervention.
      Treatment with M and M + OCP was superior to OCP regarding decreased regional fat
      mass. Baseline adiponectin and IL-6 were associated with BMI, waist, and trunk
      fat mass. Changes in trunk fat were significantly associated with changes in IL-6
      and MCP-1 during M + OCP. CONCLUSIONS: Long-term treatment with M alone or in
      combination with OCP was associated with improved body composition compared to
      OCP, whereas inflammatory markers were unchanged. OCP was not associated with
      increased inflammatory markers despite a small but significant weight gain.

PMID- 24906978
TI  - Comparison of transanal haemorrhoidal dearterialisation and stapled
      haemorrhoidopexy in management of haemorrhoidal disease: a retrospective study
      and literature review.
AB  - BACKGROUND: The aim of this study was to evaluate and compare transanal
      haemorrhoidal dearterialisation (THD) and stapled haemorrhoidopexy [also called
      procedure for prolapsed haemorrhoids (PPH)] in the management of haemorrhoidal
      disease, in terms of short-term outcomes and efficacy. METHODS: Patients
      presenting with symptomatic haemorrhoids were treated with THD. Patient
      demographics, pre-operative data, post-operative pain scores, complications,
      recurrence, and patient satisfaction scores were evaluated and recorded. Patients
      with acute thrombosed haemorrhoids, external haemorrhoids only, or other
      concomitant anal diseases were excluded. These data were compared with the
      historical data of PPH. RESULTS: Forty consecutive patients underwent THD from
      February 2012 to July 2013 and were compared to 37 patients who underwent PPH
      taken from a medical records database. There were no significant differences in
      terms of demographic data, type of anaesthesia, operative time, and blood loss.
      Length of hospital stay, time to first post-operative bowel movement, and
      complications were similar between the two groups. The median pain score after
      THD and PPH was 1.71 and 5.00, respectively, on a scale of 0-10 (10 = worst
      possible pain) (p = 0.000). There was a significant improvement in bleeding and
      prolapse scores after THD. THD patients had an earlier return to normal daily
      activities (3.13 vs. 6.78 days, p = 0.001) when compared with the PPH group. Upon
      follow-up, patients in both groups had similar satisfaction scores, and
      complication and recurrence rates. CONCLUSIONS: Both THD and PPH appear to be
      safe procedures for haemorrhoidal disease, and they appear to have similar short
      term outcomes. In particular, THD seems to be associated with a lower pain score
      than PPH, an earlier return to normal daily activities, and similar rates of
      complication and recurrence.

PMID- 24906979
TI  - Transfection of exogenous rotavirus rearranged RNA segments in cells infected
      with a WT rotavirus results in subsequent gene rearrangements.
AB  - Group A rotaviruses, members of the family Reoviridae, are a major cause of
      infantile acute gastroenteritis. The rotavirus genome consists of 11 dsRNA
      segments. In some cases, an RNA segment is replaced by a rearranged RNA segment,
      which is derived from its standard counterpart by partial sequence duplication.
      It has been shown that some rearranged segments are preferentially encapsidated
      into viral progenies after serial passages in cell culture. Based on this
      characteristic, a reverse genetics system was used previously to introduce
      exogenous segment 7 rearrangements into an infectious rotavirus. This study
      extends this reverse genetics system to RNA segments 5 and 11. Transfection of
      exogenous rotavirus rearranged RNA segment 5 or 11 into cells infected with a WT
      helper rotavirus (bovine strain RF) resulted in subsequent gene rearrangements in
      the viral progeny. Whilst recombinant viruses were rescued with an exogenous
      rearranged segment 11, the exogenous segment was modified by a secondary
      rearrangement. The occurrence of spontaneous rearrangements of WT or exogenous
      segments is a major hindrance to the use of this reverse genetics approach. 

PMID- 24906980
TI  - Chickens host diverse picornaviruses originated from potential interspecies
      transmission with recombination.
AB  - While chickens are an important reservoir for emerging pathogens such as avian
      influenza viruses, little is known about the diversity of picornaviruses in
      poultry. We discovered a previously unknown diversity of picornaviruses in
      chickens in Hong Kong. Picornaviruses were detected in 87 cloacal and 7 tracheal
      samples from 93 of 900 chickens by reverse transcription-PCR, with their partial
      3D(pol) gene sequences forming five distinct clades (I to V) among known
      picornaviruses. Analysis of eight genomes from different clades revealed seven
      different picornaviruses, including six novel picornavirus species (ChPV1 from
      clade I, ChPV2 and ChPV3 from clade II, ChPV4 and ChPV5 from clade III, ChGV1
      from clade IV) and one existing species (Avian encephalomyelitis virus from clade
      V). The six novel chicken picornavirus genomes exhibited distinct phylogenetic
      positions and genome features different from related picornaviruses, supporting
      their classification as separate species. Moreover, ChPV1 may potentially belong
      to a novel genus, with low sequence homologies to related picornaviruses,
      especially in the P1 and P2 regions, including the predicted L and 2A proteins.
      Nevertheless, these novel picornaviruses were most closely related to
      picornaviruses of other avian species (ChPV1 related to Passerivirus A, ChPV2 and
      ChPV3 to Avisivirus A and Duck hepatitis A virus, ChPV4 and ChPV5 to Melegrivirus
      A, ChGV1 to Gallivirus A). Furthermore, ChPV5 represented a potential recombinant
      picornavirus, with its P2 and P3 regions possibly originating from Melegrivirus
      A. Chickens are an important reservoir for diverse picornaviruses that may cross
      avian species barriers through mutation or recombination.

PMID- 24906981
TI  - Uric acid levels, kidney function, and cardiovascular mortality in US adults:
      National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999
      2002.
AB  - BACKGROUND: Chronic kidney disease (CKD) and hyperuricemia often coexist, and
      both conditions are increasing in prevalence in the United States. However, their
      shared role in cardiovascular risk remains highly debated. STUDY DESIGN: Cross
      sectional and longitudinal. SETTING & PARTICIPANTS: Participants in the National
      Health and Nutrition Examination Survey (NHANES) from 1988 to 2002 (n = 10,956);
      data were linked to mortality data from the National Death Index through December
      31, 2006. PREDICTORS: Serum uric acid concentration, categorized as the sex
      specific lowest (< 25th), middle (25th- < 75th), and highest (>= 75th)
      percentiles; and kidney function assessed by estimated glomerular filtration rate
      (eGFR) based on the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin
      C equation and urinary albumin-creatinine ratio (ACR). OUTCOMES: Cardiovascular
      death and all-cause mortality. RESULTS: Uric acid levels were correlated with
      eGFR(cr-cys) (r = -0.29; P < 0.001) and were correlated only slightly with ACR (r
      = 0.04; P < 0.001). There were 2,203 deaths up until December 31, 2006, of which
      981 were due to cardiovascular causes. Overall, there was a U-shaped association
      between uric acid levels and cardiovascular mortality in both women and men,
      although the lowest risk of cardiovascular mortality occurred at a lower level of
      uric acid for women compared with men. There was an association between the
      highest quartile of uric acid level and cardiovascular mortality even after
      adjustment for potential confounders (HR, 1.48; 95% CI, 1.13-1.96), although this
      association was attenuated after adjustment for ACR and eGFR(cr-cys) (HR, 1.25;
      95% CI, 0.89-1.75). The pattern of association between uric acid levels and all
      cause mortality was similar. LIMITATIONS: GFR not measured; mediating events were
      not observed. CONCLUSIONS: High uric acid level is associated with cardiovascular
      and all-cause mortality, although this relationship was no longer statistically
      significant after accounting for kidney function.

PMID- 24906982
TI  - The etiology of the association between child antisocial behavior and maternal
      negativity varies across aggressive and non-aggressive rule-breaking forms of
      antisocial behavior.
AB  - There is a robust association between negative parenting and child antisocial
      behavior problems. However, the etiology of this association remains unclear.
      Extant literature has reported strikingly different conclusions across studies,
      with some highlighting genetic mediation and others highlighting environmental
      mediation. One possible reason for these discrepancies across studies may be the
      failure to differentiate between aggressive and non-aggressive (rule-breaking)
      dimensions of childhood antisocial behavior, given their notably different
      etiologies and developmental trajectories (Burt 2012). The current study sought
      to examine the phenotypic and etiologic associations of maternal negativity with
      aggressive and rule-breaking antisocial behavior, respectively. Participants
      included 824 mothers and their twin children between the ages of 6 and 10. Our
      results highlighted clear etiologic distinctions in the associations of
      aggression and rule-breaking with maternal negativity. Aggression was associated
      with maternal negativity via both genetic and environmental factors, whereas the
      association between non-aggressive rule-breaking and maternal negativity was
      entirely environmental in origin. These findings provide additional support for
      the presence of meaningful distinctions between aggressive and non-aggressive
      forms of antisocial behavior, and highlight the complex relationship between
      parenting and child outcome. 

PMID- 24906983
TI  - Regenerative therapy with mesenchymal stem cells at the site of malignant primary
      bone tumour resection: what are the risks of early or late local recurrence?
AB  - PURPOSE: There is concern that regenerative cell-based therapies at the site of
      malignant primary bone tumours could result in increased risk of local tumour
      recurrence. We therefore investigated the long-term risks for site-specific
      recurrences in patients who had received an autologous bone marrow derived
      mesenchymal stem cell suspension to improve healing at the host-to-allograft bone
      junction of the reconstruction after bone tumour resection. METHODS: A total of
      92 patients were treated from 1993 to 2003 with bone marrow-derived mesenchymal
      stem cells after bone tumour resection. Patients were monitored for cancer
      incidence from the date of first operation (1993) until death, or until 31
      December 2013. The mean follow-up time was 15.4 years (range ten to 20 years).
      The average number of MSCs returned to the patient was 234,000 MSCs +/- 215,000.
      The primary outcome was to evaluate the risk of tumorigenesis recurrence at the
      cell therapy treatment sites with radiographs and/or MRIs. The relative risk of
      cancer recurrence was expressed as the ratio of observed and expected number of
      cases according to three different control populations. RESULTS: Thirteen
      recurrences were found at the treatment sites among the 92 patients. The expected
      number of recurrences based on incidence in the three cohort populations was
      between 15 and 20 for the same cancer, age and sex distribution. The standardized
      incidence ratio (equal to observed cancers divided by expected cancers) for the
      entire follow-up period and for all recurrences was between 0.65 and 0.86 (95 %
      CI 0.60-1.20). CONCLUSION: This study found no increased cancer local recurrence
      risk in patients after application of autologous cell-based therapy using bone
      marrow-derived mesenchymal stem cells at the treatment site after an average
      follow-up period of 15.4 years, ranging from ten to 20 years.

PMID- 24906984
TI  - Analytical applications of microbial fuel cells. Part II: Toxicity, microbial
      activity and quantification, single analyte detection and other uses.
AB  - Microbial fuel cells were rediscovered twenty years ago and now are a very active
      research area. The reasons behind this new activity are the relatively recent
      discovery of electrogenic or electroactive bacteria and the vision of two
      important practical applications, as wastewater treatment coupled with clean
      energy production and power supply systems for isolated low-power sensor devices.
      Although some analytical applications of MFCs were proposed earlier (as
      biochemical oxygen demand sensing) only lately a myriad of new uses of this
      technology are being presented by research groups around the world, which combine
      both biological-microbiological and electroanalytical expertises. This is the
      second part of a review of MFC applications in the area of analytical sciences.
      In Part I a general introduction to biological-based analytical methods including
      bioassays, biosensors, MFCs design, operating principles, as well as, perhaps the
      main and earlier presented application, the use as a BOD sensor was reviewed. In
      Part II, other proposed uses are presented and discussed. As other microbially
      based analytical systems, MFCs are satisfactory systems to measure and integrate
      complex parameters that are difficult or impossible to measure otherwise, such as
      water toxicity (where the toxic effect to aquatic organisms needed to be
      integrated). We explore here the methods proposed to measure toxicity, microbial
      metabolism, and, being of special interest to space exploration, life sensors.
      Also, some methods with higher specificity, proposed to detect a single analyte,
      are presented. Different possibilities to increase selectivity and sensitivity,
      by using molecular biology or other modern techniques are also discussed here. 

PMID- 24906985
TI  - Assessment of selenium toxicity on the life cycle of Caenorhabditis elegans.
AB  - Selenium (Se) is a growing problem of global concern. Se can cause adverse
      effects on reproductive systems, which have been linked to declines in animal
      populations. The soil nematode Caenorhabditis elegans (C. elegans) is a
      ubiquitous soil organism that is increasingly utilized as a model organism in
      aquatic and soil toxicology. In the present study, the experimental data for
      individual body length, survival rate, brood size, and hatching rate were used to
      evaluate the possible effects of selenite [Se(IV)] on C. elegans. A stage
      classified matrix model was applied to the experimental data to provide
      information on the population dynamics of C. elegans and to assess the Se(IV)
      affected asymptotic population growth rate. Estimates of the survival probability
      showed significant decreases in survival at all stages when C. elegans was
      exposed to Se(IV). The growth probability of C. elegans in the L1 stage showed
      the most significant decline, from 0.11 h(-1) (for the control) to 0.04 h(-1)
      [for exposure to 3 mM Se(IV)]. These results showed that Se(IV) has a profound
      impact on C. elegans population dynamics. The asymptotic population growth rate
      (lambda) was found to range from 1.00 to 0.64 h(-1) for increasing Se(IV)
      concentrations, implying a potential risk of population decrease for C. elegans
      exposure to a Se(IV)-contaminated environment. Our study shows how a mechanistic
      view based on the Se(IV) effects on the soil nematode C. elegans can promote a
      life cycle toxicity assessment. An important implication of this analysis is that
      mathematical models can be used to produce a population stage structure, to give
      clarity to the analysis of the key population-level endpoint (the asymptotic
      population growth rate) of population dynamics, and to evaluate the influences
      for the response of other species to environmental Se. These models sequentially
      provide candidate environmental criteria for the evaluation of the population
      impact of Se.

PMID- 24906987
TI  - Black hole restenosis after drug-eluting stent implantation for in-stent
      restenosis: potential mechanism and optimal strategy.
AB  - In-stent restenosis (ISR) has long remained as the major limitation of coronary
      stenting. The use of drug-eluting stent (DES) reduces the risk of repeat
      revascularization without an increase of death and myocardial infarction,
      compared to the standard bare metal stents. DES has also demonstrated markedly to
      reduce ISR for complex lesions. However, ISR after DES implantation still occurs
      and optimal treatment for ISR after DES has not been established. Herein, we
      report 3 cases with black hole restenosis confirmed by intravascular ultrasound
      at the site of overlapped DES and discuss potential mechanism and optimal
      strategy for this phenomenon. 

PMID- 24906986
TI  - Residency exposures and anticipated future involvement in community settings.
AB  - OBJECTIVE: To assess how exposures to community activities in residency impact
      anticipated future involvement in community child health settings. METHODS:
      Prospective cohort study of pediatric residents from 10 programs (12 sites) who
      completed training between 2003 and 2009. Residents reported annual participation
      for >= 8 days in each of 7 community activities (eg, community settings, child
      health advocacy) in the prior year. At the start and end of residency, residents
      reported anticipated involvement in 10 years in 8 community settings (eg, school,
      shelter). Anticipated involvement was dichotomized: moderate/substantial ("high")
      versus none/limited ("low"). Logistic regression modeled whether residency
      exposures independently influenced anticipated future involvement at the end of
      residency. RESULTS: A total of 683 residents completed surveys at the start and
      end of residency (66.8% participation). More than half of trainees reported >= 8
      days' of involvement in community settings (65.6%) or child health advocacy
      (53.6%) in residency. Fewer anticipated high involvement in at least 1 community
      setting at the end of residency than at the start (65.5% vs 85.6%, P < .001).
      Participation in each community activity mediated but did not moderate relations
      between anticipated involvement at the start and end of residency. In
      multivariate models, exposure to community settings in residency was associated
      with anticipated involvement at end of residency (adjusted odds ratio 1.5; 95%
      confidence interval 1.2, 2.0). No other residency exposures were associated.
      CONCLUSIONS: Residents who anticipate high involvement in community pediatrics at
      the start of residency participate in related opportunities in training. Exposure
      to community settings during residency may encourage community involvement after
      training.

PMID- 24906988
TI  - Molecular cloning and characterization of lactate dehydrogenase gene from Eimeria
      tenella.
AB  - Lactate dehydrogenase (LDH) is a key enzyme in the glycolytic pathway and is
      crucial for parasite survival. In this study, we cloned and expressed the LDH of
      Eimeria tenella (EtLDH). Real-time polymerase chain reaction and Western blot
      analysis revealed that the expression of EtLDH was developmentally regulated at
      the messenger RNA (mRNA) and protein levels. EtLDH mRNA levels were higher in
      second-generation merozoites than in other developmental stages (unsporulated
      oocysts, sporulated oocysts, and sporozoites). EtLDH protein expression levels
      were most prominent in second-generation merozoites, moderately expressed in
      unsporulated oocysts and sporulated oocysts, and weakly detected in sporozoites.
      Immunostaining with anti-recombinant EtLDH (rEtLDH) antibody indicated that EtLDH
      was mainly located in the anterior region in free sporozoites and became
      concentrated in the anterior region of intracellular sporozoites except for the
      apex after invasion into DF-1 cells. Specific staining of EtLDH protein was more
      intense in trophozoites and immature first-generation schizonts, but decreased in
      mature first-generation schizonts. Inhibition of EtLDH function using specific
      antibodies cannot efficiently reduce the ability of E. tenella sporozoites to
      invade host cells. These results suggest that EtLDH may be involved in glycolysis
      during the first-generation merogony stage in E. tenella and has little role in
      host invasion. 

PMID- 24906989
TI  - In vitro and in vivo activity of major constituents from Pluchea carolinensis
      against Leishmania amazonensis.
AB  - The search for new therapeutic agents from natural sources has been a constant
      for the treatment of diseases such as leishmaniasis. Herein, in vitro and in vivo
      pharmacological activities of pure major phenolic constituents (caffeic acid,
      chlorogenic acid, ferulic acid, quercetin, and rosmarinic acid) from Pluchea
      carolinensis against Leishmania amazonensis are presented. Pure compounds showed
      inhibitory activity against promastigotes (IC50 = 0.2-0.9 MUg/mL) and
      intracellular amastigotes (IC50 = 1.3-2.9 MUg/mL). Four of them were selected
      after testing against macrophages of BALB/c mice: caffeic acid, ferulic acid,
      quercetin, and rosmarinic acid, with selective indices of 11, 17, 10, and 20,
      respectively. Ferulic acid, rosmarinic acid, and caffeic acid controlled lesion
      size development and parasite burden in footpads from BALB/c experimentally
      infected mice, after five injections of compounds by intralesional route at 30
      mg/kg every 4 days. Pure compounds from P. carolinensis demonstrated
      antileishmanial properties.

PMID- 24906990
TI  - Trypanosoma cruzi-secreted vesicles have acid and alkaline phosphatase activities
      capable of increasing parasite adhesion and infection.
AB  - Trypanosoma cruzi virulence factors include molecules expressed on the cell
      surface as well as those secreted or shed into the extracellular medium.
      Phosphatase activities modulate different aspects of T. cruzi infection, although
      no studies to date addressed the presence and activity of phosphatases in
      vesicles secreted by this parasite. Here, we characterized acidic and alkaline
      secreted phosphatase activities of human-infective trypomastigote forms of T.
      cruzi from the Y strain and the CL-Brener clone. These are widely studied T.
      cruzi strains that represent "opposite ends of the spectrum" regarding both in
      vitro and in vivo behavior. Ecto-phosphatase activities were determined in live
      parasites, and secreted phosphatase activities were analyzed in soluble protein
      (SP) and vesicular membrane fractions (VFs) of parasite-conditioned medium. Our
      analysis using different phosphatase inhibitors strongly suggests that vesicles
      secreted by Y strain (VF(Y)) and CL-Brener (VF(CLB)) trypomastigotes are derived
      mostly from the cell surface and from exosome secretion, respectively.
      Importantly, our results show that the acid phosphatase activities in vesicles
      secreted by trypomastigotes are largely responsible for the VF-induced increase
      in adhesion of Y strain parasites to host cells and also for the VF-induced
      increase in host cell infection by CL-Brener trypomastigotes.

PMID- 24906991
TI  - First molecular characterization of enteric protozoa and the human pathogenic
      microsporidian, Enterocytozoon bieneusi, in captive snakes in China.
AB  - Enteric protozoa are frequently found in snakes. Nevertheless, few studies
      regarding genetic characterization of these parasites have been carried out. We
      describe here the first molecular survey of protozoan pathogens from snakes in
      China and the first report on Enterocytozoon bieneusi genotyping in snakes in the
      world. Here, 240 fecal specimens were collected from two species of captive
      snakes, Naja naja (Indian cobra) and Ptyas mucosus (Oriental rat snake), in
      Guangxi Province, China, and examined by PCR amplification of the small subunit
      ribosomal RNA of enteric protozoa and the internal transcribed spacer of
      ribosomal RNA of E. bieneusi. Cryptosporidium serpentis was identified in three
      specimens (2.1%) of Oriental rat snakes. Caryospora was found in 5.4% specimens,
      including eight from cobras (8.1%) and five from rat snakes (3.6%), and
      represented six new species-Caryospora sp. SKC-2014a to Caryospora sp. SKC-2014
      f. Three new Eimeria species, Eimeria sp. SKE-2014a to Eimeria sp. SKE-2014c,
      were detected in three specimens (2.1%) from rat snakes. Additionally,
      Sarcocystis sp. SKS-2014 was detected in one specimen from a cobra. The infection
      rates of E. bieneusi were 3.0% in cobras and 5.7% in rat snakes. Sequence
      analysis of 11 PCR products revealed the presence of six E. bieneusi genotypes
      two known genotypes (type IV and Henan V) and four new genotypes (CRep-1 to CRep
      4). All six E. bieneusi genotypes belonged to the zoonotic group (group 1). This
      result raised the possibility that E. bieneusi could be present in animals
      consumed by snakes. This should be taken into consideration to better understand
      the diversity of the parasite, its transmission through the predator-prey
      relationship, and public health implications.

PMID- 24906992
TI  - Dirofilaria repens and Dirofilaria immitis DNA findings in mosquitoes in Germany:
      temperature data allow autochthonous extrinsic development.
AB  - After the repeated demonstration of Dirofilaria repens infections in German dogs,
      D. repens and Dirofilaria immitis DNA was detected in mosquitoes trapped in 2011,
      2012 and 2013 in northeastern and southwestern Germany within the framework of
      culicid monitoring projects. As temperature is the most important factor
      dictating the extrinsic development of dirofilarial larvae in the potential
      vector, data of the German Weather Service (DWD) were analysed for the regions
      where the positive mosquitoes had been collected. Based on the mean daily
      temperatures recorded by weather stations most closely to the collection sites of
      the mosquitoes, it can be concluded that the mosquitoes were trapped in time
      periods that allowed for the completion of the developmental cycle of the worms
      in the mosquitoes and a subsequent transmission to a vertebrate host. The results
      of this study confirm the principal climatic suitability of certain German
      regions for the establishment of natural dirofilarial transmission cycles.
      Moreover, the theoretical climatic considerations, together with findings of D.
      repens infections in German dogs and mosquitoes, strongly suggest that the
      continuing spread of at least D. repens from its traditional habitats in the
      Mediterranean has reached southwestern and northeastern Germany. 

PMID- 24906993
TI  - Gene expression profile of LPS-stimulated dendritic cells induced by a
      recombinant Sj16 (rSj16) derived from Schistosoma japonicum.
AB  - Sj16, a 16-kDa protein secreted from Schistosoma japonicum, has been demonstrated
      an anti-inflammatory effect in vitro and in vivo, but its mechanism is still not
      clear. In this study, microarray analysis was performed to investigate the
      effects of recombinant Sj16 (rSj16) on the gene expression of the
      lipopolysaccharide (LPS)-stimulated dendritic cells (DCs). Immature DCs were
      treated with LPS, LPS + recombinant Sj16 (rSj16), or rSj16 alone for 24 h, and
      the gene expression profiles were examined using complementary DNA (cDNA)
      microarrays. With the cutoff value of 2-fold change in the expression, 509 genes
      were affected, 226 genes upregulated, and 283 genes downregulated after adding
      rSj16. Analysis by functional annotation clustering tool showed that rSj16
      affected genes mainly associated with inflammatory response, defense response,
      regulation of immune system process, apoptosis, and cell migration. The results
      revealed that rSj16 reduced the LPS-induced pro-inflammatory genes such as
      cytokines (e.g., IL6, IL18, IFN-gamma, IL12a, IL1b), chemokines, and receptors
      (e.g., CXCL1, CXCL9, CCL5, CCR5, CCR1, CCR2, CXCR3) and increased the anti
      inflammatory gene IL-10. Further data mining of these genes by pathway analysis
      showed that genes regulated by rSj16 were significantly involved in cytokine
      cytokine receptor interaction, NOD-like receptor signaling pathway, Toll-like
      receptor signaling pathway, antigen processing and presentation, and Jak-STAT
      signaling pathway. In addition, quantitative real-time PCR (qRT-PCR) and Western
      blot analysis showed that rSj16 downregulated the expression of inhibitor of
      nuclear factor kappa-beta kinase subunit beta (IKKbeta) and nuclear factor-kappa
      beta p65 (NF-kappabeta) messenger RNA (mRNA) and inhibited the phosphorylation of
      IKKbeta and the NF-kappaB p65 protein, which implied that rSj16 exerting
      immunomodulatory effects by suppressing NF-kappaB signaling pathway. These
      results provide useful information in further understanding of the
      immunoregulation mechanisms of Sj16, and it is indicated that Sj16 could be as a
      potential molecule for the immunosuppressant drug development.

PMID- 24906995
TI  - Performance objectives for Salmonella in fresh pork meat intended to be eaten
      cooked: how to derive them and verify their achievement.
AB  - In our study we aimed at deriving performance objectives (POs) for Salmonella in
      fresh pork meat intended to be eaten cooked, using loin chop as a model.
      Moreover, sampling plans to verify the compliance of meat lots to such POs are
      presented. Ten lots of product, collected in the same slaughterhouse along a one
      year period, were tested for Salmonella detection under four different storage
      stages through the product shelf life. The POs were considered as different
      target values from Salmonella prevalence and were calculated at the 50th
      percentile of prevalence distributions under each stage. Results obtained
      indicated that values increased between a minimum of 26.10% of positives after
      final storage at 14 degrees C to a maximum of 46.70% of positives after storage
      at retail. The number of samples to be tested in order to detect at least one
      positive and verify the compliance to the estimated POs ranged between five, for
      samples after storage at retail, and ten, for samples stored at 14 degrees C
      before the expiration date. For risk management purposes, percentiles different
      from the 50th can be selected in order to derive the POs as well as the number of
      samples to be tested in order to verify their fulfillment. Thus, the approach
      presented in this paper offers different options to risk managers for improving
      the decision-making process. 

PMID- 24906994
TI  - Systemic and local mucosal immune responses induced by orally delivered Bacillus
      subtilis spore expressing leucine aminopeptidase 2 of Clonorchis sinensis.
AB  - Human clonorchiasis caused by Clonorchis sinensis (C. sinensis) has been
      increasingly prevalent in recent years so that an effective measure is essential
      and urgent to control the infectious disease. Oral delivery of antigens from C.
      sinensis may be an important approach to effectively induce both systemic and
      local immune responses to anti-infection of the parasite. In the current study,
      we used Bacillus subtilis (B. subtilis) spores as a delivery vehicle to introduce
      leucine aminopeptidase 2 of C. sinensis (CsLAP2), an excretory/secretory antigen
      with high immunogenicity, expressing on their surface. SDS-PAGE, western
      blotting, and flow cytometry indicated that CsLAP2 was successfully expressed on
      the surface of B. subtilis spores (CotC-CsLAP2 spores). BALB/c mice were treated
      with spores intragastrically. On day 31 after the treatment, we found that mice
      intragastrically treated with CotC-CsLAP2 spores exhibited higher IgG, IgG1,
      IgG2a, and IgA level in sera as well as higher sIgA level in bile and intestinal
      lavage fluid compared to mice orally administrated with spores not expressing
      CsLAP2 (CotC spores) and naive mice. The peak titer of IgG/IgA presented on day
      31/49 after oral administration. IgG1 level was lower than IgG2a in group
      administrated with CotC-CsLAP2 spores. sIgA-secreting cells were obviously
      observed in intestinal epithelium of mice orally treated with CotC-CsLAP2 spores.
      After incubated with CotC-CsLAP2, the levels of IFN-gamma, IL-6, IL-10, IL-17A,
      and TNF significantly increased in the supernatant of splenocytes isolated from
      mice orally treated with CotC-CsLAP2 spores, while there was no statistically
      significant difference of IL-4 level representing Th2 response among the groups.
      Our study demonstrated that oral administration of CsLAP2 delivered by B.
      subtilis spore elicited obvious systemic and local mucosal immunity. Secretory
      IgA and Th1-Th17 cellular immunity might involved in mechanisms of the immune
      response. 

PMID- 24906996
TI  - Interrupted aortic arch in an active, asymptomatic adult.

PMID- 24906997
TI  - Regional left ventricular function after transapical vs. transfemoral
      transcatheter aortic valve implantation analysed by cardiac magnetic resonance
      feature tracking.
AB  - AIMS: This study analysed the impact of transapical (TA) vs. transfemoral (TF)
      access site transcatheter aortic valve implantation (TAVI) on post-procedural
      regional left ventricular (LV) function using cardiac magnetic resonance (CMR)
      feature tracking (FT). METHODS AND RESULTS: CMR was performed 3 months after TAVI
      on 44 consecutive patients with normal LV ejection fraction prior to TAVI. Twenty
      patients had TA-TAVI, and 24 had TF-TAVI. Standard cine imaging was performed in
      three standard cardiac long-axis views (two-, four- and three-chamber views).
      Myocardial peak systolic radial strain (PSRS) and peak systolic longitudinal
      strain (PSLS) were analysed based on CMR-FT considering 49 segments in each of
      the three views. There were no differences in PSRS and PSLS for the basal and mid
      ventricular segments between TA- and TF-TAVI groups. In contrast, PSRS and PSLS
      of apical segments and apical cap were reduced in the TA- compared with the TF
      TAVI group (PSRS: 15.7 +/- 6.4 vs. 35.9 +/- 15.7%, respectively, P < 0.001; PSLS:
      -8.9 +/- 5.3 vs. -16.9 +/- 4.3%, respectively, P < 0.001). Comparison of all non
      apical segments vs. apical segments and apical cap demonstrated no difference in
      the TF group (PSRS: 34.6 +/- 9.0 vs. 35.9 +/- 15.7%; respectively, P = 0.702;
      PSLS: -17.8 +/- 4.6 vs. -16.9 +/- 4.3%; respectively, P = 0.802). After TA-TAVI,
      PSRS and PSLS of the apical segments were reduced compared with the non-apical
      segments (PSRS: 15.7 +/- 6.4 vs. 33.5 +/- 7.0%, respectively, P < 0.001; PSLS: 
      8.9 +/- 5.3 vs. -15.5 +/- 3.5%, respectively, P < 0.001). CONCLUSION: Apical LV
      function abnormalities can be detected at 3-month follow-up in all TA-TAVI
      patients using CMR-FT. TA-TAVI results in significant impairment of apical LV
      function compared with TF-TAVI.

PMID- 24906998
TI  - Quantitative analysis of intraventricular blood flow dynamics by
      echocardiographic particle image velocimetry in patients with acute myocardial
      infarction at different stages of left ventricular dysfunction.
AB  - AIMS: Left ventricular (LV) diastolic filling is characterized by the formation
      of a vortex that supports an efficient transit into systolic ejection. Aim of
      this study was to assess the intraventricular (IV) blood flow dynamics among
      patients with ST elevated myocardial infarction (STEMI) at different degrees of
      LV dysfunction, in the attempt to find novel indicators of LV pump efficiency.
      METHODS AND RESULTS: Sixty-four subjects, 34 consecutive STEMI patients and 30
      healthy controls, underwent before hospital discharge 2D speckle tracking
      echocardiography to assess global longitudinal strain (GLS), and echo-particle
      image velocimetry analysis to assess flow energetic parameters. Left ventricular
      volumes ejection fraction (LVEF) and global wall motion score index (GWMSI) were
      evaluated by 3D echocardiography. ST elevated myocardial infarction patients were
      subdivided into three groups according to LVEF. Energy dissipation, vorticity
      fluctuation, and kinetic energy fluctuation indexes, which characterize the
      degree of disturbance in the flow, exhibit a biphasic behaviour in STEMI patients
      when compared with controls, with the highest values in patients with still
      preserved LV function and progressive lower values with LV function worsening.
      Significant linear correlations were found between energy dissipation index and
      both LVEF and GLS (r = 0.57, P < 0.001 and r = -0.61, P = 0.001, respectively).
      Kinetic energy fluctuation index significantly correlates with both LVEF (r =
      0.75, P < 0.001) and GLS (-0.58, P = 0.002). Finally, a significant correlation
      was observed between GWMSI and energy dissipation index (-0.56, P = 0.008).
      CONCLUSIONS: The present study describes, for the first time, the progression of
      IV flow energetic properties in patients with acute myocardial infarction at
      different stages of LV dysfunction when compared with healthy controls. Further
      data are needed to assess the role of these parameters in the development and
      maintenance of LV dysfunction.

PMID- 24906999
TI  - Black men who have sex with men, sexual risk-taking, and willingness to use rapid
      home HIV tests.
AB  - The availability of rapid home-based HIV testing (RHT) in the USA has provided us
      with a valuable, new option in our efforts to identify more people living with
      HIV and to do so sooner. Furthermore, it is possible that RHT will be or is
      currently being used as a means of learning one's own and one's partner's HIV
      status prior to engaging in condomless intercourse. Data regarding knowledge and
      willingness to use RHT, however, is very limited. In particular, no studies have
      investigated RHT use among Black men who have sex with men (BMSM). Understanding
      RHT use among BMSM is critical as we have observed alarming rates of HIV
      prevalence among this group, and RHT may provide an opportunity to slow HIV
      transmission among BMSM. In order to better understand RHT, we assessed
      knowledge, willingness to use and actual use of RHT, HIV testing history,
      substance use, and sexual risk-taking among 387 HIV-negative BMSM and 157 HIV
      positive BMSM attending a community event in the southeastern USA. We used
      generalized linear modeling to assess factors associated with their willingness
      to use RHT. Although familiarity with the availability of RHT was somewhat
      limited among these men, a substantial portion of BMSM did report an interest in
      using RHT, including with their sex partners. Among HIV-negative BMSM, however,
      we found a negative relationship between willingness to use RHT and sexual risk
      taking, i.e., higher numbers of condomless anal sex acts were associated with a
      reduction in willingness to use RHT. It appears that men who report the greatest
      risk-taking for HIV are least interested in RHT. Future research should focus on
      better understanding concerns regarding RHT among at-risk HIV-negative men and
      should investigate the usefulness of using RHT as a HIV prevention method. 

PMID- 24907000
TI  - Enteral nutrition in the hemodynamically unstable critically ill patient.
AB  - The benefit of enteral nutrition in critically ill patients has been demonstrated
      by several studies, especially when it is started early, in the first 24-48h of
      stay in the Intensive Care Unit, and this practice is currently advised by the
      main clinical guidelines. The start of enteral nutrition is controversial in
      patients with hemodynamic failure, since it may trigger intestinal ischemia.
      However, there are data from experimental studies in animals, as well as from
      observational studies in humans that allow for hypotheses regarding its
      beneficial effect and safety. Interventional clinical trials are needed to
      confirm these findings. 

PMID- 24907001
TI  - The relationship between motivation, monetary compensation, and data quality
      among US- and India-based workers on Mechanical Turk.
AB  - In this study, we examined data quality among Amazon Mechanical Turk (MTurk)
      workers based in India, and the effect of monetary compensation on their data
      quality. Recent studies have shown that work quality is independent of
      compensation rates, and that compensation primarily affects the quantity but not
      the quality of work. However, the results of these studies were generally based
      on compensation rates below the minimum wage, and far below a level that was
      likely to play a practical role in the lives of workers. In this study,
      compensation rates were set around the minimum wage in India. To examine data
      quality, we developed the squared discrepancy procedure, which is a task-based
      quality assurance approach for survey tasks whose goal is to identify inattentive
      participants. We showed that data quality is directly affected by compensation
      rates for India-based participants. We also found that data were of a lesser
      quality among India-based than among US participants, even when optimal payment
      strategies were utilized. We additionally showed that the motivation of MTurk
      users has shifted, and that monetary compensation is now reported to be the
      primary reason for working on MTurk, among both US- and India-based workers.
      Overall, MTurk is a constantly evolving marketplace where multiple factors can
      contribute to data quality. High-quality survey data can be acquired on MTurk
      among India-based participants when an appropriate pay rate is provided and task
      specific quality assurance procedures are utilized. 

PMID- 24907002
TI  - Multiple-group analysis approach to testing group difference in indirect effects.
AB  - This article introduces five methods that take a multiple-group analysis approach
      to testing a group difference in indirect effects. Unlike the general frameworks
      for testing moderated indirect effects, the five methods provide direct tests for
      equality of indirect effects between groups. A simulation study was conducted to
      examine the performance of the methods in terms of the empirical type I error
      rate, statistical power, and coverage of 95 % confidence intervals. The
      likelihood ratio test and percentile bootstrap confidence intervals are
      recommended. The methods are illustrated using an empirical data set. 

PMID- 24907003
TI  - The stochastically curtailed generalized likelihood ratio: A new termination
      criterion for variable-length computerized classification tests.
AB  - Computerized classification tests (CCTs) are used to classify examinees into
      categories in the context of professional certification testing. The term
      "variable-length" refers to CCTs that terminate (i.e., cease administering items
      to the examinee) when a classification can be made with a prespecified level of
      certainty. The sequential probability ratio test (SPRT) is a common criterion for
      terminating variable-length CCTs, but recent research has proposed more efficient
      methods. Specifically, the stochastically curtailed SPRT (SCSPRT) and the
      generalized likelihood ratio criterion (GLR) have been shown to classify
      examinees with accuracy similar to the SPRT while using fewer items. This article
      shows that the GLR criterion itself may be stochastically curtailed, resulting in
      a new termination criterion, the stochastically curtailed GLR (SCGLR). All four
      criteria-the SPRT, SCSPRT, GLR, and the new SCGLR-were compared using a
      simulation study. In this study, we examined the criteria in testing conditions
      that varied several CCT design features, including item bank characteristics,
      pass/fail threshold, and examinee ability distribution. In each condition, the
      termination criteria were evaluated according to their accuracy (proportion of
      examinees classified correctly), efficiency (test length), and loss (a single
      statistic combing both accuracy and efficiency). The simulation results showed
      that the SCGLR can yield increased efficiency without sacrificing accuracy,
      relative to the SPRT, SCSPRT, and GLR in a wide variety of CCT designs. 

PMID- 24907004
TI  - Transhiatal esophagectomy after previous right pneumonectomy.

PMID- 24907005
TI  - Interstitial tumor-associated macrophages combined with tumor-derived colony
      stimulating factor-1 and interleukin-6, a novel prognostic biomarker in non-small
      cell lung cancer.
AB  - OBJECTIVES: Recent experimental evidence has indicated that interstitial tumor
      associated macrophages (TAMs), tumor-derived macrophage colony-stimulating factor
      (also known as CSF-1), and interleukin-6 (IL-6) interact in the pathogenesis of
      malignant epithelial tumors, including lung cancer. The present study aimed to
      explore their relationship and prognostic significance in surgically resected non
      small cell lung cancer (NSCLC). METHODS: Tissue microarray and
      immunohistochemistry were used to detect the expression of CSF-1, IL-6, and CD68
      positive TAMs in 417 patients with NSCLC undergoing complete pulmonary resection
      from 2003 to 2008. Their correlations and clinicopathologic data were analyzed
      using chi-square testing. Their prognostic values were evaluated by univariate
      Kaplan-Meier survival analysis and multivariate Cox proportional hazard model
      analysis. RESULTS: The expression of CSF-1 and IL-6 in NSCLC correlated
      positively with the infiltration degree of TAMs in the tumor stroma (r=0.184 and
      r=0.196, respectively; P<.001). The expression of both CSF-1 and IL-6 was
      statistically significant for survival (P<.001). Nevertheless, no such
      relationship was observed for CD68 in the tumor stroma (P>.05). When CSF-1 and/or
      IL-6 and CD68 were taken into consideration together, the result became
      statistically significant. Multivariate analysis showed that co-expression of
      CD68, CSF-1, and IL-6 remained the most significant and independent prognostic
      factor for survival (P<.05) but not the combinations of CSF-1 and IL-6, CD68 and
      CSF-1, or CD68 and IL-6 (P>.05). The 5-year survival rate in the CD68-negative
      and CSF-1- and IL-6-positive group was better than the rate in the CD68, CSF-1-,
      and IL-6-positive group (P<.05). CONCLUSIONS: The combination of CD68 plus TAMs,
      CSF-1, and IL-6 is very likely to be a valuable independent predictor of survival
      in patients with NSCLC. Perhaps co-expression of CSF-1 and IL-6 induces
      interstitial TAMs to shift toward the tumor-promoting phenotype.

PMID- 24907006
TI  - [Stereotactic ablative irradiation for lung cancer].
AB  - Stereotactic radiotherapy for lung cancer is a technique that is now well
      established in the therapeutic arsenal. Protocols are effective, with very high
      local control rate and an acceptable rate of survival if one takes into account
      the patient's age and comorbidities. Complications are rare. This review of the
      literature analyses the whole process of the therapeutic indications and future
      prospects. 

PMID- 24907007
TI  - Non-union site debridement increased the efficacy of rhBMP-2 in a rodent model.
AB  - In our study we investigated the influence of debridement on bone healing in a
      rodent critical size defect model with and without rhBMP-2 in fibrin matrix. A
      total of 58 male Sprague-Dawley rats underwent a first surgical procedure where a
      femoral osteotomy was performed. In the single step group the defect remained
      empty and the specimens were collected 4 weeks later. A silicone spacer was
      implanted to inhibit bone healing within the defect in all the other groups. At 4
      weeks the spacer was removed in a second operation with and without debridement
      of the bone ends and fibrin matrix alone or combined with 10 MUg rhBMP-2 were
      applied. 4 weeks after the primary operation those specimens were collected. All
      the specimens were evaluated by MUCT scans and histological analysis. Debridement
      of the defect significantly increased bone volume in the animals treated with
      rhBMP-2. In the control groups without growth factor application the effect of
      debridement was not significant concerning the union rate and the bone volume. In
      our experimental setting surgical debridement of the non-union site particularly
      promoted bone healing in combination with BMP-2 administration in fibrin matrix.

PMID- 24907008
TI  - Pulmonary embolism following ankle fractures treated without an operation - an
      analysis using National Health Service data.
AB  - The majority of ankle fractures are stable and can be treated without an
      operation, most commonly with cast immobilisation. Based on concerns regarding
      the risk of a venous thromboembolic event (VTE) while immobilised, there is
      currently debate as to whether these patients should receive VTE prophylaxis for
      the duration of treatment. Rates of pulmonary embolism (PE) in this patient group
      are unknown. This retrospective cohort study was designed to identify patients
      treated without an operation for ankle fracture and determine the occurrence of
      PE and inpatient mortality within 90 days of injury using the English National
      Health Service administrative databases. Logistic regression models were used to
      assess the influence of age, gender and Charlson co-morbidity score on these
      outcomes. We identified 14777 adult patients over a 54-month period (April 2007
      September 2011) that met our linkage and inclusion criteria (isolated, unilateral
      closed ankle fracture that did not require hospitalisation). Mean age was 46.4
      years (range 18-99) and the majority had a Charlson 0 score (97.7%). There were
      32 (0.22%) PEs within 90 days of the fracture (including in one patient who
      subsequently died). After adjustment, Charlson score of >=1 was associated with a
      greater risk of PE (Odds ratio = 11.97, p < 0.001) compared to Charlson 0. Risk
      for these patients was 2.08%. In total, fifteen patients (0.11%) died in hospital
      within 90 days. Pulmonary embolism is rare following ankle fractures treated
      without an operation. Patients with multiple co-morbidities are at a higher risk.
      Based on this evidence, an ankle fracture treated without an operation does not
      appear to be an indication for routine VTE prophylaxis.

PMID- 24907009
TI  - Computed tomography to detect life-threatening injuries in trauma: can we (and
      should we) add in patients' preferences?

PMID- 24907010
TI  - Risk of injury to the axillary nerve during antegrade proximal humeral blade nail
      fixation - an anatomical study.
AB  - INTRODUCTION: The antegrade intramedullary Locking Blade Nail (Marquardt,
      Germany) is a device aimed at improving purchase in the humeral head and reducing
      varus displacement by providing medial buttress support and triangular stability
      within the humeral head. The aim of this study is to measure the relationship of
      the proximal fixation screws to the axillary nerve. METHODS: 13 whole cadavers
      underwent insertion of an antegrade proximal humeral blade nail via a deltoid
      split approach to both shoulders. The anatomic proximity of the anterior branch
      of the axillary nerve to the screws was measured following soft tissue dissection
      and inspection of the nerve. RESULTS: The mean distance of the nerve from the
      anterolateral acromion was 62 mm (range 45-81 mm). The nerve lay closest to the
      distal blade fixation screw 4.9 mm (range 0-19 mm). In three cases the nerve lay
      directly underneath the washer and in all three cases there was macroscopic
      evidence of damage to the nerve. In 5 cases the nerve travelled obliquely in a
      cranial direction to lie 1.8 mm (range 0-3 mm) from the distal blade fixation
      screw, in 2 of these cases the nerve lay beneath the washer. CONCLUSION: The
      anterior branch of the axillary nerve is placed at risk during insertion of the
      locking screws despite use of protection sleeves and trocars. We advocate that
      when using antegrade intramedullary nails that incorporate an inferomedial calcar
      screw an extended anterolateral acromial approach is undertaken.

PMID- 24907011
TI  - Acute promyelocytic leukemia.

PMID- 24907012
TI  - Understanding the molecular pathogenesis of acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia
      (AML) associated with peculiar biologic and clinical features and requiring
      specific management. At the genetic level, APL is featured by a unique chromosome
      translocation t(15;17) which results in the PML-RARalpha gene fusion and chimeric
      protein. APL is the first example of differentiation therapy targeted to a
      defined genetic target i.e. PML-RARalpha. PML-RARalpha behaves as an altered
      retinoic acid receptor with an ability of transmitting oncogenic signaling
      leading to accumulation of undifferentiated promyelocytes. All-trans-retinoic
      acid (ATRA) induces disease remission in APL patients by triggering terminal
      differentiation of leukemic promyelocytes. More recently, arsenic trioxide (ATO)
      has been shown to contribute degradation of the PML-RARalpha oncoprotein through
      bonding the PML moiety and has shown excellent synergism with ATRA in clinical
      trials. Elucidating the oncogenic signaling of PML-RARalpha through various
      transcription factors and the study of APL mouse models have greatly helped to
      understand the molecular pathogenesis of APL. However, the precise molecular
      mechanism by which t(15;17) is formed and initiates leukemia remains unknown.
      While transforming oncogenic potential of PML-RARalpha has been described
      extensively, the mechanistic events important for the formation of t(15;17) have
      been taken from the model of Therapy-related APL (t-APL). 

PMID- 24907013
TI  - The coagulopathy in acute promyelocytic leukaemia--what have we learned in the
      past twenty years.
AB  - Coagulopathy is a unique component of the pathology of acute promyelocytic
      leukaemia (APL). Though many causative factors have been elucidated, therapies to
      rectify the coagulopathy are far from being realised. Thrombotic and bleeding
      complications remain the major causes of early deaths. In this chapter, the known
      causes of abnormalities in haemostatic function, namely the coagulopathy and
      changes in the fibrinolytic system, will be reviewed. Major risk factors for
      these complications are identified. Current available measures for correction of
      the coagulopathy and their effectiveness are critically examined. Unless the
      coagulopathy can be effectively controlled, bleeding complications will remain an
      obstacle to achieving a cure for this disease. The issues that need to be
      addressed in next phase of investigations are also discussed. 

PMID- 24907014
TI  - Triple A therapy: the molecular underpinnings of the unique sensitivity of
      leukemic promyelocytes to anthracyclines, all-trans-retinoic acid and arsenic
      trioxide.
AB  - If looking for a mnemonic to remember the relevant facts about acute
      promyelocytic leukemia (APL), one just has to remember that APL is a disease of
      A's. It is acute and it is highly sensitive to treatment with anthracyclines, all
      trans-retinoic acid (RA) and arsenic trioxide (ATO). The presence of fusions
      involving the retinoic acid receptor alpha (RARA) is without question the central
      player driving APL and dictating the response of this disease to these
      therapeutic agents. However, beyond this knowledge, the molecular mechanisms that
      contribute to the complicated pathogenesis and the response to treatment of APL
      are not completely defined. As more is understood about this hematological
      malignancy, there are more opportunities to refine and improve treatment based on
      this knowledge. In this review article, we discuss the response of APL to these
      "A" therapies. 

PMID- 24907015
TI  - Conventional induction and post-remission therapy in APL: have we arrived?
AB  - Since the introduction of all-trans-retinoic acid, the use of this molecularly
      targeted treatment in combination with anthracycline-based chemotherapy has
      completely changed the prognosis of acute promyelocytic leukemia (APL) turning it
      into the most curable acute myeloid leukemia. Also, the use of risk-adapted
      protocols has optimized the drug combination and the most appropriate dose
      intensity for each subset of patients classified according to both risk of
      relapse and vulnerability to drug toxicity. Recent developments have included the
      investigation of the role of arsenic trioxide (ATO) as front-line treatment after
      its success in relapsed APL, both to minimize or even omit the use of cytotoxic
      agents and to reinforce the conventional chemotherapy-based approach. In the
      present chapter we will address the achievements of conventional treatment with
      ATRA and chemotherapy, as well as the opportunity to cure more patients with
      modifications of this therapeutic backbone with the addition of ATO in any phase
      of treatment. 

PMID- 24907016
TI  - Have all-trans retinoic acid and arsenic trioxide replaced all-trans retinoic
      acid and anthracyclines in APL as standard of care.
AB  - Until recently, the standard of care in the treatment of APL has involved the
      combination of all-trans retinoic acid with anthracycline-based chemotherapy
      during both induction and consolidation. Additionally, the intensity of
      consolidation chemotherapy has evolved according to a universally accepted
      relapse-risk stratification algorithm based on the white cell and platelet counts
      at presentation. That standard of care is being challenged by the increasing
      incorporation of arsenic trioxide into front-line treatment protocols, based on
      two complementary observations. The first is the undoubted anti-leukaemic
      activity of arsenic trioxide as shown in the relapsed and refractory setting, and
      in the initial management of low- and intermediate-risk patients. The second is
      an improved understanding of the action of both all-trans retinoic acid and
      arsenic trioxide in mediating APL cell eradication, with increasing recognition
      that PML-RARA fusion protein degradation rather than direct induction of terminal
      differentiation is the primary mechanism for their ability to eliminate leukaemia
      initiating cells. As a result, we believe the standard of care for initial
      therapy in APL is shifting towards an all-trans retinoic acid plus arsenic
      trioxide-based approach, with additional chemotherapy reserved for patients with
      high-risk disease. 

PMID- 24907017
TI  - Can we say farewell to monitoring minimal residual disease in acute promyelocytic
      leukaemia?
AB  - Molecularly targeted therapies have transformed the management of PML-RARA+ acute
      promyelocytic leukaemia (APL), with survival rates now exceeding 80% in clinical
      trials. This raises questions about the relevance of post-remission monitoring
      for PML-RARA transcripts, which has been widely used to predict relapse, guiding
      early intervention to prevent disease progression and the inherent risk of fatal
      bleeding. Given the treatability of haematological relapse, survival benefits
      would only be seen if monitoring could identify patients who could be salvaged if
      treated early but not later on, although it could be argued that early deployment
      of arsenic trioxide (ATO) can avoid inducing hyperleucocytosis and the associated
      differentiation syndrome, which frequently complicate treatment of frank relapse.
      However, given the low rates of relapse now observed in patients presenting with
      standard risk disease (i.e. presenting WBC<10*10(9)/l) who achieve early
      molecular remission, subsequent sequential minimal residual disease (MRD)
      monitoring confers only a marginal benefit, so could be avoided in this group.
      However, sequential MRD monitoring may still be of value in patients with high
      risk APL, although evidence tends to come from historically controlled studies.
      Therefore, there may remain a role for MRD monitoring in the most clinically
      challenging subsets of APL, but the continuing debate highlights the need for
      robust evidence in developing a more individualized approach to management of
      other subtypes of acute leukaemia.

PMID- 24907018
TI  - Extramedullary disease in APL: a real phenomenon to contend with or not?
AB  - In the last 2 decades an increasing number of patients reported with
      extramedullary involvement among relapsed acute promyelocytic leukemia (APL)
      patients. Several investigators related this phenomenon to the relatively new
      treatment of all-trans-retinoic-acid (ATRA). In this review article we will
      examine what has been reported in the medical literature on extramedullary
      disease in APL: the common sites to be involved, the clinical risk factors to its
      development, the role of ATRA and arsenic tri-oxide and the recommended
      treatment. 

PMID- 24907019
TI  - Treatment of paediatric APL: how does the therapeutic approach differ from
      adults?
AB  - Acute promyelocytic leukaemia (APL) in children and adolescents shares many
      features with APL in adults. There are important distinctions, however, between
      these age groups in the presentation, complications and treatment outcomes.
      Paediatric patients are more likely to present with high risk features including
      elevated WBC count or microgranular variant (M3v). Yet the early death rate is
      lower in paediatric patients compared to adult patients. Overall outcomes such as
      CR, OS and EFS appear similar in paediatric and adult patients treated on similar
      regimens except that very young children may have a higher risk of relapse. While
      contemporary studies have clearly demonstrated improved survival in adults
      receiving ATO therapy, currently there is more limited data on the role of ATO in
      paediatric patients. Here we highlight the similarities and important
      distinctions between paediatric and adult APL while reviewing available data on
      treatment of paediatric APL. 

PMID- 24907020
TI  - Subclinical atherosclerosis determinants in morbid obesity.
AB  - BACKGROUND AND AIMS: Obesity is associated with increased cardiovascular risk.
      However, the impact of morbid obesity on vascular structure and function is not
      well understood. This study was designed to appraise subclinical atherosclerosis
      markers, including carotid intima media thickness (cIMT), endothelial function,
      and arterial wall stiffness, and their determinants, in morbidly obese patients.
      METHODS AND RESULTS: In this cross-sectional study 194 overweight and obese
      patients were distributed in morbid-obese patients (MOP, n = 110), obese (OP, n =
      84) and overweight patients (OwP, n = 33) groups. Demography, anthropometry,
      clinical and standard biochemical data were recorded. cIMT, endothelial function,
      defined as the small artery reactivity index (saRHI), and artery wall rigidity,
      studied by the augmentation index, were determined. More than 50% of the MOP, OP
      and OwP had a cIMT above the 75th percentile per age and gender. No differences
      in cIMT or saRHI were observed, although overweight and obese patients (OOP) had
      higher arterial rigidity compared with the morbid-obese patients. In a
      multivariate regression test, while cholesterol was the main determinant of cIMT
      in overweight and obese patients, glucose metabolism was the determinant in MOP.
      CONCLUSION: More than half of the population have a cIMT above general population
      ranges. OwP, OP and MOP have similar cIMT and saRHI. However, OOP have greater
      arterial wall rigidity. Dysglycemia is the main factor associated with
      subclinical atherosclerosis in MOP.

PMID- 24907021
TI  - Lower Helicobacter pylori infection rate in chronic kidney disease and end-stage
      renal disease patients with peptic ulcer disease.
AB  - BACKGROUND: Distinguishing the rates of Helicobacter pylori infection in chronic
      kidney disease (CKD) and end-stage renal disease (ESRD) patients with peptic
      ulcer disease (PUD) from that in PUD patients without CKD is critical. METHODS:
      We first stratified the original 1 million study population according to CKD or
      ESRD. We retrospectively investigated the incidence of H. pylori infection in PUD
      patients with or without CKD or ESRD between 2000 and 2008 in a nationwide,
      population-based cohort using data from the Taiwan National Health Insurance
      Research Database. The comparison cohort consisted of PUD patients without CKD. A
      logistic regression model was used to calculate the odds ratios (ORs) and 95%
      confidence intervals, to determine whether the occurrence of H. pylori infection
      in CKD or ESRD patients with PUD differed from that of PUD patients without CKD.
      RESULTS: Among the CKD patients, 261 patients had H. pylori-positive and 185 H.
      pylori-negative peptic ulcers. Among the ESRD patients, 81 had H. pylori-positive
      and 63 H. pylori-negative peptic ulcers. Among the non-CKD control patients, 1658
      patients had H. pylori-positive and 702 H. pylori-negative peptic ulcers. Our
      results revealed a lower H. pylori infection rate in CKD (OR = 0.64, p < 0.001)
      and ESRD (OR = 0.54, p = 0.001) patients with PUD than in PUD patients without
      CKD. CONCLUSION: The H. pylori infection rate is lower in PUD patients with CKD
      and ESRD than in those without CKD.

PMID- 24907022
TI  - Update on treatment of gastric cancer.
AB  - Surgery is the main treatment for curing gastric cancer. Early diagnosis provides
      an excellent survival outcome via an improved detection of early gastric cancer
      and an improved resection rate. The extent of lymphadenectomy surgery has been
      under debate for a long time. In East Asian countries, especially Japan, Korea,
      and Taiwan, gastrectomy with D2 dissection is routinely performed. By contrast,
      in most Western countries, gastrectomy with D1 dissection is performed, due to
      lower mortality and morbidity. Recently, acceptance of D2 surgery has increased
      in Western countries because: (1) modified D2 lymphadenectomy (preservation of
      pancreas and spleen) improves operative morbidity and mortality; (2) Western
      surgeons can be trained to performed D2 lymph node dissection on Western patients
      safely; and (3) D2 resection decreases locoregional recurrence and prolongs
      survival. Current guidelines in the United States and Europe suggest modified D2
      dissection is recommended, but needs to be performed by high-volume centers with
      experienced surgeons. Adjuvant or perioperative chemotherapy should be prescribed
      for gastric cancer with Stage II or III disease, due to its marked benefits of
      reducing disease recurrence and increasing long-term survival. Patients with
      inoperable advanced gastric cancer should receive chemotherapy to improve their
      survival and quality of life if an acceptable performance status can be achieved.
      Targeted therapy with trastuzumab should be considered in patients with HER-2/neu
      overexpression who have a higher response rate and a longer survival. 

PMID- 24907024
TI  - Development, validation, and utility of an instrument to assess core competencies
      in the Leadership Education in Neurodevelopmental and Related Disabilities (LEND)
      program.
AB  - To describe the development and psychometric evaluation of the Core Competency
      Measure (CCM), an instrument designed to assess professional competencies as
      defined by the Maternal Child Health Bureau (MCHB) and targeted by Leadership
      Education in Neurodevelopmental and Related Disabilities (LEND) programs. The CCM
      is a 44-item self-report measure comprised of six subscales to assess clinical,
      interdisciplinary, family-centered/cultural, community, research, and
      advocacy/policy competencies. The CCM was developed in an iterative fashion
      through participatory action research, and then nine cohorts of LEND trainees (N
      = 144) from 14 different disciplines completed the CCM during the first week of
      the training program. A 6-factor confirmatory factor analysis model was fit to
      data from the 44 original items. After three items were removed, the model
      adequately fit the data (comparative fit indices = .93, root mean error of
      approximation = .06) with all factor loadings exceeding .55. The measure was
      determined to be quite reliable as adequate internal consistency and test-retest
      reliability were found for each subscale. The instrument's construct validity was
      supported by expected differences in self-rated competencies among fellows
      representing various disciplines, and the convergent validity was supported by
      the pattern of inter-correlations between subscale scores. The CCM appears to be
      a reliable and valid measure of MCHB core competencies for our sample of LEND
      trainees. It provides an assessment of key training areas addressed by the LEND
      program. Although the measure was developed within only one LEND Program, with
      additional research it has the potential to serve as a standardized tool to
      evaluate the strengths and limitations of MCHB training, both within and between
      programs.

PMID- 24907023
TI  - Strategies to increase the donor pool and access to kidney transplantation: an
      international perspective.
AB  - In this position article, DESCARTES (Developing Education Science and Care for
      Renal Transplantation in European States) board members describe the current
      strategies aimed at expanding living and deceased donor kidney pools. The article
      focuses on the recent progress in desensitization and kidney paired exchange
      programmes and on the expanded criteria for the use of donor kidneys and organs
      from donors after circulatory death. It also highlights differences in policies
      and practices across different regions with special regard to European Union
      countries. Living donor kidney paired exchange, the deceased donor Acceptable
      Mismatch Programme and kidneys from donors after circulatory death are probably
      the most promising innovations for expanding kidney transplantation in Europe
      over the coming decade. To maximize success, an effort is needed to standardize
      transplant strategies, policies and legislation across European countries. 

PMID- 24907025
TI  - Latarjet, Bristow, and Eden-Hybinette procedures for anterior shoulder
      dislocation: systematic review and quantitative synthesis of the literature.
AB  - PURPOSE: The aim of this study was to evaluate clinical outcome, rate of
      recurrence, complications, and rate of postoperative osteoarthritis in patients
      with anterior shoulder instability managed with Latarjet, Bristow, or Eden
      Hybinette procedures. METHODS: A systematic review of the literature on
      management of anterior dislocation of the shoulder with glenoid bony procedures
      was performed. A comprehensive search of PubMed, MEDLINE, CINAHL, Cochrane,
      EMBASE, and Google Scholar databases using various combinations of the keywords
      "shoulder," "dislocation," "treatment," "Latarjet," "Bristow," "bone loss," "Eden
      Hybinette," "iliac," "bone," "block," "clinical," "outcome," and "Bankart." The
      following data were extracted: demographics, bone defects and other lesions, type
      of surgery, outcome measurement, range of motion (ROM), recurrence of
      instability, complications, and osteoarthritis. A quantitative synthesis of all
      comparative studies was performed to compare bone block procedures and Bankart
      repair in terms of postoperative recurrence of instability and osteoarthritis.
      RESULTS: Forty-six studies were included and 3,211 shoulders were evaluated. The
      mean value of the Coleman Methodology Score (CMS) was 65 points. Preoperatively,
      the injuries detected most were glenoid bone loss and Bankart lesions. The Eden
      Hybinette procedure had the highest rate of postoperative osteoarthritis and
      recurrence. Pooled results from comparative studies showed that the bone block
      procedures were associated with a lower rate of recurrence when compared with
      Bankart repair (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.28 to
      0.74; P = .002), whereas there was no significant difference between the 2 groups
      in terms of postoperative osteoarthritis (P = .79). CONCLUSIONS: The open Bristow
      Latarjet procedure continues to be a valid surgical option to treat patients with
      anterior shoulder instability. Bone block procedures were associated with a lower
      rate of recurrence when compared with the Bankart repair. The Eden-Hybinette
      procedure has clinical outcomes very similar to the Bristow-Latarjet technique
      but has a higher rate of postoperative osteoarthritis and recurrence. An
      arthroscopic Bristow-Latarjet procedure seems to be better in terms of prevention
      of recurrence and rehabilitation, but randomized studies are needed to reach
      definitive conclusions. LEVEL OF EVIDENCE: Level IV, systematic review of Level
      II, III, and IV studies.

PMID- 24907026
TI  - Tibial tunnel placement accuracy during anterior cruciate ligament
      reconstruction: independent femoral versus transtibial femoral tunnel drilling
      techniques.
AB  - PURPOSE: This study aimed to compare the accuracy of tibial tunnel placement
      using independent femoral (IF) versus transtibial (TT) techniques. METHODS: Ten
      matched pairs of cadaveric knees were randomized so that one knee in the pair
      underwent arthroscopic TT drilling of the femoral tunnel and the other underwent
      IF drilling through an accessory medial portal. For both techniques, an attempt
      was made to place the femoral and tibial tunnels as close to the center of the
      respective anterior cruciate ligament (ACL) footprints as possible. Preoperative
      and postoperative computed tomography using a technique optimized for ligament
      evaluation allowed comparison of the anatomic ACL tibial footprint to the tibial
      tunnel aperture. The percentage of tunnel aperture contained within the native
      footprint, as well as the distance from the center of the tunnel aperture to the
      center of the footprint, was measured. Additionally, graft obliquity relative to
      the tibial plateau was evaluated in the sagittal plane. RESULTS: The percentage
      of tibial tunnel aperture contained within the native footprint averaged 71.6% +/
      17.2% versus 52.1% +/- 23.4% (P = .04) in the IF and TT groups, respectively.
      The distance from the center of the footprint to the center of the tibial tunnel
      aperture was 3.50 +/- 1.6 mm and 4.40 +/- 1.7 mm (P = .27) in the IF and TT
      groups, respectively. TT drilling placed 6 of 10 tunnels posterior to the center
      of the footprint versus 3 of 10 tunnels in IF drilling. The graft obliquity
      angles were 54.8 degrees  in TT specimens and 47.5 degrees  in IF specimens (P =
      .09). CONCLUSIONS: This study adds to the literature suggesting that TT drilling
      with an 8-mm reamer has deleterious effects on tibial tunnel aperture and
      position. IF drilling, which does not involve repeated reaming of the tibial
      tunnel, is associated with the placement of a higher percentage of the tunnel
      aperture within the native tibial footprint. There was not a significant
      difference between the IF and TT techniques in their ability to place the center
      of the tibial aperture near the center of the footprint or in graft obliquity.
      CLINICAL RELEVANCE: ACL reconstruction has continued to evolve in an attempt to
      restore the functional anatomy and biomechanical behavior of the knee. Tibial
      tunnel characteristics-such as location, aperture topography, and tunnel
      obliquity-are important factors to consider in ACL reconstruction. This study
      compares tibial tunnels after IF and TT techniques.

PMID- 24907027
TI  - Febrile convulsions increase risk of Tourette syndrome.
AB  - PURPOSE: Febrile convulsion (FC) and Tourette syndrome (TS) are both common
      neurological disorders in infants and children. Both disorders share clinical
      similarities, such as paroxysmal symptoms with normal neurodevelopment and
      expected remission over time. This population-based study investigated the
      association between FC with TS during childhood neurodevelopment. METHOD: We used
      the Taiwan National Health Insurance Research Database to conduct a retrospective
      cohort analysis on 1586 FC patients. A reference cohort of 6344 non-FC patients,
      matched for age, sex, urbanization level, parental occupation, and index year,
      was used for comparison. The risk of the occurrence of TS in FC patients was
      assessed using a Cox proportional hazard regression model. RESULTS: The overall
      incidence of TS was higher in the FC cohort than in the non-FC cohort (28.5 vs
      13.9 per 10,000 person-years; adjusted hazard ratio=1.91, 95% confidence
      interval=1.32-2.75). The associated risk factors for FC patients to develop TS
      were boys, children living in rural areas, and children whose parents held blue
      collar positions. Moreover, the risk of TS in FC patients rose from 0.89 to 16.0
      (trend test P<0.0001) when the frequency of FC-related medical visits increased
      from 1 to 2 times to more than 4 times. The adjusted hazard ratio for TS in
      related to FC-related medical visits was 1.02 (95% CI=1.02-1.03) per one
      frequency increment. CONCLUSION: FC may increase the risk of subsequent TS
      occurrence in children. Children who had frequent medical visits for FC were
      particularly vulnerable.

PMID- 24907028
TI  - Amelioration of capillary regression and atrophy of the soleus muscle in hindlimb
      unloaded rats by astaxanthin supplementation and intermittent loading.
AB  - A chronic decrease in neuromuscular activity (activation and/or loading) results
      in muscle atrophy and capillary regression that are due, in part, to the
      overproduction of reactive oxygen species. We have reported that antioxidant
      treatment with astaxanthin attenuates the overexpression of reactive oxygen
      species in atrophied muscles that, in turn, ameliorates capillary regression in
      hindlimb-unloaded rats. Astaxanthin supplementation, however, had little effect
      on muscle mass and fibre cross-sectional area. In contrast, intermittent loading
      of the hindlimbs of hindlimb-unloaded rats ameliorates muscle atrophy. Therefore,
      we hypothesized that the combination of astaxanthin supplementation and
      intermittent loading would attenuate both muscle atrophy and capillary regression
      during hindlimb unloading. As expected, 2 weeks of hindlimb unloading resulted in
      atrophy, a decrease in capillary volume and a shift towards smaller-diameter
      capillaries in the soleus muscle. Intermittent loading alone (1 h of cage
      ambulation per day) attenuated atrophy of the soleus, while astaxanthin treatment
      alone maintained the capillary network to near control levels. The combination of
      intermittent loading and astaxanthin treatment, however, ameliorated atrophy of
      the soleus and maintained the capillary volume and luminal diameters and the
      superoxide dismutase-1 protein levels near control values. These results indicate
      that intermittent loading combined with astaxanthin supplementation could be an
      effective therapy for both the muscle atrophy and the capillary regression
      associated with a chronic decrease in neuromuscular activity.

PMID- 24907029
TI  - Dynamics of corticospinal changes during and after high-intensity quadriceps
      exercise.
AB  - This study tested the hypothesis that during fatiguing quadriceps exercise,
      supraspinal fatigue develops late, is associated with both increased
      corticospinal excitability and inhibition and recovers quickly. Eight subjects
      performed 20 s contractions [15 s at 50% maximal voluntary contraction (MVC)
      followed by 5 s MVC] separated by a 10 s rest period until task failure.
      Transcranial magnetic stimulation (TMS) and electrical femoral nerve stimulation
      (PNS) were delivered ~ 2 s apart during 50% MVC, during MVC and after MVC in
      relaxed muscle. Voluntary activation was assessed by TMS (VATMS) immediately
      before and after exercise and then three times over a 6 min recovery period.
      During exercise, MVC and twitch force evoked by PNS in relaxed muscle decreased
      progressively to 48 +/- 8 and 36 +/- 16% of control values, respectively (both P
      < 0.01). Significant changes in voluntary activation assessed by PNS and twitch
      evoked by TMS during MVC were observed during the last quarter of exercise only
      (from 96.4 +/- 1.7 to 86 +/- 13%, P = 0.03 and from 0.76 +/- 0.8 to 4.9 +/- 4.7%
      MVC, P = 0.02, from baseline to task failure, respectively). The TMS-induced
      silent period increased linearly during both MVC (by ~ 79 ms) and 50% MVC (by ~
      63 ms; both P < 0.01). Motor-evoked potential amplitude did not change during the
      protocol at any force levels. Both silent period and VATMS recovered within 2 min
      postexercise, whereas MVC and twitch force evoked by PNS in relaxed muscle
      recovered to only 84 +/- 9 and 73 +/- 17% of control values 6 min after exercise,
      respectively. In conclusion, high-intensity single-joint quadriceps exercise
      induces supraspinal fatigue near task failure, with increased intracortical
      inhibition and, in contrast to previous upper-limb results, unchanged
      corticospinal excitability. These changes recover rapidly after task failure,
      emphasizing the need to measure corticospinal adaptations immediately at task
      failure to avoid underestimation of exercise-induced corticospinal changes.

PMID- 24907030
TI  - Immunohistochemical distribution of cocaine and amphetamine regulatory peptide
      like immunoreactive (CART-LI) nerve fibers in the circular muscle layer and their
      relationship to other peptides in the human caecum.
AB  - Motor activity of the gastrointestinal tract is extensively controlled by the
      enteric nervous system (ENS). Numerous neurotransmitters and neuromodulators are
      responsible for this regulation. One of them is cocaine- and amphetamine
      regulated transcript peptide (CART). So far, there are few reports available
      concerning the distribution, functions, and co-localization of CART in the human
      gastrointestinal tract. The aim of the present investigation was to study the
      distribution and degree of co-localization of CART with substances taking part in
      conducting sensory stimuli, such as: substance P (SP), neurokinin A (NKA),
      calcitonin gene related peptide (CGRP) and Leu 5 enkephalin (L-ENK) in the
      circular muscle layer of the human caecum. CART-like immunoreactive (CART-LI)
      nerve fibers formed a very dense meshwork in the circular muscle layer of the
      caecum in all patients studied. Moreover, all neuronal substances tested during
      the present investigation were observed in CART-LI processes, but the degree of
      co-localization depended on the type of substance. The highest number of CART
      positive nerves also contained L-ENK. A slightly lower level of co-localization
      was observed in the case of CART and SP or NKA, while only single nerve fibers
      were simultaneously CART- and CGRP-positive. 

PMID- 24907031
TI  - Prenatal screening for intimate partner violence: a qualitative meta-synthesis.
AB  - AIM: The aim of this meta-synthesis was to glean an understanding of healthcare
      providers' experience with prenatal screening for intimate partner violence
      (IPV). BACKGROUND: Prenatal screening guidelines for IPV are in place; however, a
      gap exists between these recommendations and providers' practices. METHODS:
      Noblit and Hare's (1988) approach to synthesizing qualitative research studies
      was utilized. Eight research reports were identified and produced a sample of 142
      experienced women's healthcare providers from the United States, New Zealand, and
      Sweden. RESULTS: The synthesis revealed five overarching themes: (1) therapeutic
      relationship, (2) understanding what she is not saying, (3) presence of partner,
      (4) variations of how and when to discuss, and (5) "lost in the maze" of
      disclosure. When analyzed as a whole, the five themes contribute to a lack of
      universal screening for IPV. CONCLUSIONS: Given that IPV is a social problem with
      long-term negative sequela, providers are poised to identify women during the
      perinatal timeframe to ensure adequate referrals and services to stop the cycle
      of violence.

PMID- 24907033
TI  - Obstructive sleep apnea is associated with cancer mortality in younger patients.
AB  - OBJECTIVE: The association between obstructive sleep apnea (OSA) and cancer
      mortality has scarcely been studied. The objective of this study was to
      investigate whether OSA is associated with increased cancer mortality in a large
      cohort of patients with OSA suspicion. METHODS: This was a multicenter study in
      consecutive patients investigated for suspected OSA. OSA severity was measured by
      the apnea-hypopnea index (AHI) and the hypoxemia index (% night-time spent with
      oxygen saturation <90%, TSat90). The association between OSA severity and cancer
      mortality was assessed using Cox's proportional regression analyses after
      adjusting for relevant confounders. RESULTS: In all, 5427 patients with median
      follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with
      cancer. Log-transformed TSat90 was independently associated with increased cancer
      mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval
      [CI], 1.03-1.42), as well as in the group of patients with cancer (HR, 1.19; 95%
      CI, 1.02-1.41). The closest association was shown in patients <65years in both
      the AHI (continuous log-transformed AHI: HR, 1.87; 95% CI, 1.1-3.2; upper vs
      lower AHI tertile: HR, 3.98; 95% CI, 1.14-3.64) and the TSat90 (continuous log
      transformed TSat90: HR, 1.73; 95% CI, 1.23-2.4; upper vs. lower TSat90 tertile:
      HR, 14.4; 95% CI, 1.85-111.6). CONCLUSIONS: OSA severity was associated with
      increased cancer mortality, particularly in patients aged <65 years.

PMID- 24907032
TI  - RNA-seq analysis of the influence of anaerobiosis and FNR on Shigella flexneri.
AB  - BACKGROUND: Shigella flexneri is an important human pathogen that has to adapt to
      the anaerobic environment in the gastrointestinal tract to cause dysentery. To
      define the influence of anaerobiosis on the virulence of Shigella, we performed
      deep RNA sequencing to identify transcriptomic differences that are induced by
      anaerobiosis and modulated by the anaerobic Fumarate and Nitrate Reduction
      regulator, FNR. RESULTS: We found that 528 chromosomal genes were differentially
      expressed in response to anaerobic conditions; of these, 228 genes were also
      influenced by FNR. Genes that were up-regulated in anaerobic conditions are
      involved in carbon transport and metabolism (e.g. ptsG, manX, murQ, cysP, cra),
      DNA topology and regulation (e.g. ygiP, stpA, hns), host interactions (e.g. yciD,
      nmpC, slyB, gapA, shf, msbB) and survival within the gastrointestinal tract (e.g.
      shiA, ospI, adiY, cysP). Interestingly, there was a marked effect of available
      oxygen on genes involved in Type III secretion system (T3SS), which is required
      for host cell invasion and pathogenesis. These genes, located on the large
      Shigella virulence plasmid, were down regulated in anaerobiosis in an FNR
      dependent manner. We also confirmed anaerobic induction of csrB and csrC small
      RNAs in an FNR-independent manner. CONCLUSIONS: Anaerobiosis promotes survival
      and adaption strategies of Shigella, while modulating virulence plasmid genes
      involved in T3SS-mediated host cell invasion. The influence of FNR on this
      process is more extensive than previously appreciated, although aside from the
      virulence plasmid, this transcriptional regulator does not govern expression of
      genes on other horizontally acquired sequences on the chromosome such as
      pathogenicity islands.

PMID- 24907034
TI  - Sociodemographic and disease-related factors are associated with patient-reported
      anxiety and depression in spondyloarthritis patients in the Swedish SpAScania
      cohort.
AB  - Anxiety and depression are common among patients with rheumatic diseases. This
      study aims to explore which factors are associated with self-reported anxiety and
      depression in a well-defined cohort of spondyloarthritis (SpA) patients. In 2009,
      3,711 patients from the SpAScania cohort were sent a postal questionnaire to
      assess health-related quality of life (HRQoL) and physical and mental
      functioning. The Hospital Anxiety and Depression Scale measured anxiety (HADS-A)
      and depression (HADS-D), subscales 0-21, best-worst. HADS >=8 indicates possible
      cases of anxiety or depression. One-way ANOVA (p < 0.05) tested for differences
      among the SpA subtypes in HADS scores. Linear regression analysis adjusted for
      age, gender, and disease duration was used to test for associations between HADS
      and independent variables. In total, 2,167 (58 %) patients (52 % females, mean
      age 55.4 years) returned the questionnaire. In total, 683 (32 %) cases were
      classified as "possible anxiety" and 305 (14 %) as "possible depression" cases
      with mean (SD) HADS-A 5.9 (4.3) and HADS-D 4.4 (3.6). There were no differences
      among the SpA subtypes in HADS-A and HADS-D. HADS-A and HADS-D were associated
      with lower education, lower physical activity (HADS-D only), chronic pain
      problems, more fatigue, lower general health, lower HRQoL, lower level of
      functioning, higher disease activity, and lower self-efficacy. Associations with
      anxiety and/or depression appear multifactorial in patients with SpA including
      both personal and disease-related factors. Since these comorbidities are
      increased in SpA and treatable, they should be screened for in clinical practice,
      possibly with instruments like the HADS. 

PMID- 24907035
TI  - Survival of disease-modifying antirheumatic drugs used as the first antirheumatic
      medication in the treatment of ankylosing spondylitis in Finland. A nationwide
      population-based register study.
AB  - The tight national drug reimbursement regulations in the treatment of ankylosing
      spondylitis (AS) in Finland lead to the practice that at least one traditional
      disease-modifying antirheumatic drug (DMARD), if not contraindicated, has been
      tried and has failed before a patient can be eligible for reimbursement of anti
      tumour necrosis factor (TNF) treatment. The aim of the present study is to
      evaluate drug survival of the firstly prescribed DMARDs in patients with AS. All
      AS patients from January 1, 2000 to December 31, 2007 were collected from the
      nationwide drug reimbursement registry maintained by the Social Insurance
      Institution (SII). Data on antirheumatic medication came from the prescription
      registry of SII. A total of 2,890 AS patients (60 % males) were identified.
      Sulfasalazine (SSA) monotherapy was the most common first antirheumatic treatment
      (2,319 patients, 87 %), followed by methotrexate (MTX) monotherapy (230 patients,
      9 %) and by hydroxychloroquine monotherapy (77 patients, 3 %). A combination of
      two or more DMARDs was used by 44 patients (2 %). Only seven patients (0.3 %) had
      biological (etanercept or adalimumab) started as the first antirheumatic drug.
      Median survival time of SSA monotherapy was 4.5 years (95 % CI 4.2 to 4.8) and
      that of MTX was 1.9 years (95 % CI 1.5 to 2.1). SSA is almost the standard as the
      first antirheumatic treatment of AS in Finland. Although the clinical efficiency
      of SSA was not evaluable in the present study, these data suggest that the use of
      SSA can at least postpone the need and start of TNF inhibitors with marked
      economic consequences. 

PMID- 24907036
TI  - Time trends in total ankle arthroplasty in the USA: a study of the National
      Inpatient Sample.
AB  - The objective of this study was to assess the time trends in utilization,
      clinical characteristics, and outcomes of patients undergoing total ankle
      arthroplasty (TAA) in the USA. We used the Nationwide Inpatient Sample (NIS) data
      from 1998 to 2010 to examine time trends in the utilization rates of TAA. We used
      the Cochran Armitage test for trend to assess time trends across the years and
      the analysis of variance (ANOVA), Wilcoxon test, or chi-squared test (as
      appropriate) to compare the first (1998-2000) and the last time periods (2009
      2010). TAA utilization rate increased significant from 1998 to 2010: 0.13 to 0.84
      per 100,000 overall, 0.14 to 0.88 per 100,000 in females, and from 0.11 to 0.81
      per 100,000 in males (p < 0.0001 for each comparison for time trends). Compared
      to the 1998-2000 period, those undergoing TAA in 2009-2010 were older (41% fewer
      patients <50 years, p < 0.0001), less likely to have rheumatoid arthritis as the
      underlying diagnosis (55% fewer patients, p = 0.0001), more likely to have Deyo
      Charlson index of 2 or more (197% more, p = 0.0010), and had a shorter length of
      stay at 2.5 days (17% reduction, p < 0.0001). Mortality was rare ranging from 0
      to 0.6% and discharge to inpatient facility ranged 12.6-14.1%; we noted no
      significant time trends in either (p > 0.05). The utilization rate of TAA
      increased rapidly in the USA from 1998 to 2010, but post-arthroplasty mortality
      rate was stable. Underlying diagnosis and medical comorbidity changed over time
      and both can impact outcomes after TAA. Further studies should examine how the
      outcomes and complications of TAA have evolved over time.

PMID- 24907037
TI  - A 28-day gavage toxicity study in Fischer 344 rats with 3-methylfuran.
AB  - 3-Methylfuran is produced in foods during food processing and preservation
      techniques that involve heat treatment such as cooking, jarring, canning, and
      pasteurization. Currently, there are no studies available on the toxicity of 3
      methylfuran. We conducted a 28-day gavage toxicity study (7 days per week) using
      doses of 0.0, 0.1, 0.3, 1.5, 3.0, 6.0, 12.0, and 25.0 mg/kg bw/day in order to
      determine the dose range needed to establish a no observed adverse effect level
      and to better characterize nonneoplastic effects including those affecting
      hematology, clinical biochemistry, gross morphology, and histopathology.
      Histological changes of the liver were noted in all treated animals and gross
      changes were noted beginning at 3.0 mg/kg bw/kg. Alterations in the activity of
      serum enzymes indicative of effects on the liver were observed, including
      increases in levels of alanine transaminase and alkaline phosphatase at the
      highest dose. There was a significant increase in serum thyroxine (T4) and
      triiodothyronine (T3), which was not accompanied by histological changes in the
      thyroid. For the most part, statistically significant changes were seen only at
      the highest dose for hematology and at the 2 highest doses for clinical chemistry
      parameters. In contrast, mild histological lesions in the liver were observed
      even at the lowest dose of 0.1 mg/kg bw/day. 

PMID- 24907039
TI  - Do successful agers live longer? The Vitality 90+ study.
AB  - OBJECTIVE: To discover whether successful aging, understood as a multidimensional
      concept, predicts further survival in very old people. METHOD: The population
      sample consisted of 1,370 persons aged 90 or over in the Vitality 90+ study. Four
      alternative models of successful aging were constructed, each of them consisting
      of physical, psychological, and social dimensions. Mortality was followed up
      after 4 and 7 years. RESULTS: Three out of four models significantly predicted
      survival at both follow-ups for the whole group. Separately, "success" in the
      physical, psychological, and social components was also associated with higher
      survival. The associations were stronger in women than in men. DISCUSSION:
      Successful aging, measured using physical, psychological, and social dimensions,
      predicts the length of future life in nonagenarians.

PMID- 24907040
TI  - Purification and characterization of paraoxonase 1 (PON1) from Swiss Black,
      Holstein, and Montofon bovines.
AB  - Paraoxonase 1 (PON1: EC 3.1.8.1) is a calcium-dependent enzyme associated with
      high-density lipoproteins (HDLs) and has a protective effect against oxidation of
      low-density lipoproteins (LDLs) in mammals. PON1 is the best-studied member of a
      family of enzymes called serum paraoxonases, or PONs, identified in mammals and
      other vertebrates as well as in invertebrates. PONs exhibit a range of important
      activities, including drug metabolism and detoxification of organophosphates such
      as nerve agents. This study reports, for the first time, purification and
      biochemical characterization of serum PON1 from different bovine breeds namely
      Swiss Black, Holstein, and Montofon. Bovine serum PON1s were purified using
      ammonium sulfate precipitation followed by Sepharose-4B-L-tyrosine-1
      naphthylamine hydrophobic interaction chromatography. SDS-polyacrylamide gel
      electrophoresis of the purified enzymes indicates a single band with an apparent
      MW of 43 kDa. The purified enzymes had a specific activity of 10.78, 27.00, and
      22.38 U/mg for Swiss Black, Holstein, and Montofon bovines, respectively. The
      overall purification rates of our method were 262.47-, 2,476.90-, and 538.06-fold
      for Swiss Black, Holstein, and Montofon bovines, respectively. Furthermore, using
      phenyl acetate as a substrate, we determined the K M and V max values of the
      purified enzymes, as 0.80 mM, 1428.5 U/ml for Swiss Black; 0.40 mM, 714.3 U/ml
      for Holstein; and 0.50 mM, 1,111.1 U/ml for Montofon bovine. The present study
      has revealed that there is no substantial difference in PON1 activities among the
      studied bovine breeds. 

PMID- 24907041
TI  - Significance of satellite DNA revealed by conservation of a widespread repeat DNA
      sequence among angiosperms.
AB  - The analysis of plant genome structure and evolution requires comprehensive
      characterization of repetitive sequences that make up the majority of plant
      nuclear DNA. In the present study, we analyzed the nature of pCtKpnI-I and
      pCtKpnI-II tandem repeated sequences, reported earlier in Carthamus tinctorius.
      Interestingly, homolog of pCtKpnI-I repeat sequence was also found to be present
      in widely divergent families of angiosperms. pCtKpnI-I showed high sequence
      similarity but low copy number among various taxa of different families of
      angiosperms analyzed. In comparison, pCtKpnI-II was specific to the genus
      Carthamus and was not present in any other taxa analyzed. The molecular structure
      of pCtKpnI-I was analyzed in various unrelated taxa of angiosperms to decipher
      the evolutionary conserved nature of the sequence and its possible functional
      role. 

PMID- 24907042
TI  - Chemical- and thermal-induced unfolding of Leishmania donovani ribose-5-phosphate
      isomerase B: a single-tryptophan protein.
AB  - Ribose-5-phosphate isomerase B (RpiB), a crucial enzyme of pentose phosphate
      pathway, was proposed to be a potential drug target for visceral leishmaniasis.
      In this study, we have analyzed the biophysical properties of Leishmania donovani
      RpiB (LdRpiB) enzyme to gain insight into its unfolding pathway under various
      chemical and thermal denaturation conditions by using fluorescence and CD
      spectroscopy. LdRpiB inactivation precedes the structural transition at lower
      concentrations of both urea and guanidine hydrochloride (GdHCl). 8
      Anilinonapthalene 1-sulfonic (ANS) binding experiments revealed the presence of
      molten globule intermediate at 1.5 M GdHCl and a nonnative intermediate state at
      6-M urea concentration. Acrylamide quenching experiments further validated the
      above findings, as solvent accessibility of tryptophan residues increased with
      increase in GdHCl and urea concentration. The recombinant LdRpiB was completely
      unfolded at 6 M GdHCl, whereas the enzyme molecule was resistant to complete
      unfolding even at 8-M urea concentration. The GdHCl- and urea-mediated unfolding
      involves a three-state transition process. Thermal-induced denaturation revealed
      complete loss of enzyme activity at 65  degrees C with only 20 % secondary
      structure loss. The formation of the well-ordered beta-sheet structures of
      amyloid fibrils was observed after 55  degrees C which increased linearly till 85
      degrees C as detected by thioflavin T dye. This study depicts the stability of
      the enzyme in the presence of chemical and thermal denaturants and stability
      activity relationship of the enzyme. The presence of the intermediate states may
      have major implications in the way the enzyme binds to its natural ligand under
      various conditions. Also, the present study provides insights into the properties
      of intermediate entities of this important enzyme. 

PMID- 24907043
TI  - Isolation, purification, and characterization of antimicrobial compound 6-[1,2
      dimethyl-6-(2-methyl-allyloxy)-hexyl]-3-(2-methoxy-phenyl)-chromen-4-one from
      Penicillium sp. HT-28.
AB  - A fungal culture (Penicillium sp., HT-28), isolated from soil has been evaluated
      for its bioactivity, which showed broad spectrum antimicrobial activity and was
      effective against methicillin-resistant Staphylococcus aureus (MRSA) also.
      Statistical optimization of the medium by response surface methodology (RSM)
      enhanced the antimicrobial activity up to 1.8-fold. Column chromatography was
      used to isolate the active compound (A), which was characterized to be 6-[1,2
      dimethyl-6-(2-methyl-allyloxy)-hexyl]-3-(2-methoxy-phenyl)-chromen-4-one by
      various spectroscopic techniques such as infrared (IR), (1)H and (13)C nuclear
      magnetic resonance (NMR) spectra, and mass spectroscopy. Minimum inhibitory
      concentration (MIC) of the active compound (A) ranged from 0.5 to 15 MUg/mL.
      Viable cell count studies of the active compound (A) showed S. aureus,
      Escherichia coli, Staphylococcus epidermidis, and Salmonella typhimurium 1 to be
      the most sensitive. The compound retained its bioactivity after treating it at
      100  degrees C for 1 h. Furthermore, the compound (A) when tested for its
      biosafety was found neither to be cytotoxic nor mutagenic. The study demonstrated
      that an apparently novel compound isolated from Penicillium sp. (HT-28) seems to
      be a stable and potent antimicrobial.

PMID- 24907044
TI  - Flow injection analysis biosensor for urea analysis in urine using enzyme
      thermistor.
AB  - There is a need for analytical methods capable of monitoring urea levels in urine
      for patients under clinical monitoring to appraise renal function. Herein, we
      present a practical method to quantify levels of urea in human urine samples
      using flow injection analysis-enzyme thermistor (FIA-ET) biosensor. The biosensor
      comprises a covalently immobilized enzyme urease (Jack bean) on aminated silica
      support, which selectively hydrolyzes the urea present in the sample. Under
      optimized conditions, the developed biosensor showed a linear response in the
      range of 10-1,000 mM, R (2) = 0.99, and response time of 90 s in 100 mM phosphate
      buffer (PB) (flow rate of 0.5 mL/min, sample volume of 0.1 mL, and pH 7.2). The
      urea-spiked human urine samples showed minimal matrix interference in the range
      of 10-1,000 mM. Recoveries were obtained (92.26-99.80 %) in the spiked urine
      samples. The reliability and reproducibility of the developed biosensor were
      found satisfactory with percent relative standard deviation (% RSD) = 0.741. The
      developed biosensor showed excellent operational stability up to 30 weeks with 20
      % loss in original response when used continuously at room temperature. These
      results indicate that the developed biosensor could be very effective to detect
      low and high levels of urea in urine samples. 

PMID- 24907045
TI  - Global identification of CobB interactors by an Escherichia coli proteome
      microarray.
AB  - Protein acetylation is one of the most abundant post-translational modifications
      and plays critical roles in many important biological processes. Based on the
      recent advances in mass spectrometry technology, in bacteria, such as Escherichia
      coli, tremendous acetylated proteins and acetylation sites have been identified.
      However, only one protein deacetylase, i.e. CobB, has been identified in E. coli
      so far. How CobB is regulated is still elusive. One right strategy to study the
      regulation of CobB is to globally identify its interacting proteins. In this
      study, we used a proteome microarray containing ~4000 affinity-purified E. coli
      proteins to globally identify CobB interactors, and finally identified 183
      binding proteins of high stringency. Bioinformatics analysis showed that these
      interacting proteins play a variety of roles in a wide range of cellular
      functions and are highly enriched in carboxylic acid metabolic process and hexose
      catabolic process, and also enriched in transferase and hydrolase. We further
      used bio-layer interferometry to analyze the interaction and quantify the kinetic
      parameters of putative CobB interactors, and clearly showed that CobB could
      strongly interact with TopA and AccC. The novel CobB interactors that we
      identified could serve as a start point for further functional analysis. 

PMID- 24907047
TI  - Externalizing disorders and substance use: empirically derived subtypes in a
      population-based sample of adults.
AB  - PURPOSE: Attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD),
      and oppositional defiant disorder (ODD) are common externalizing disorders of
      childhood. The common effects of these disorders on substance abuse need further
      investigation. The current study investigated the joint clusters of
      childhood/adolescence ADHD, CD, and ODD, and their influence on substance
      abuse/dependence in a population-based sample of adults. METHODS: The data were
      drawn from the PsyCoLaus study (n = 3,720) conducted in Lausanne, Switzerland.
      The population-based sample included 238 subjects meeting criteria for
      ADHD/ODD/CD diagnoses before the age of 15. Latent class analyses (LCA) were
      performed to derive comorbidity subtypes, which were subsequently characterized
      with respect to psychosocial correlates and substance use. RESULTS: The best fit
      in LCAs was achieved with three latent classes: an ADHD subtype (35.7 %); an
      externalizing multimorbid subtype (33.6 %) involving ODD, ADHD, and CD; and a
      third subtype with CD (30.7 %). The CD subtype showed the highest association
      with substance use. Apart from this, the externalizing multimorbid subtype was
      also significantly linked to substance use. The ADHD subtype had only elevated
      frequencies for alcohol dependence in comparison with subjects that had no
      history of ADHD, ODD, and CD during childhood or adolescence. Finally, important
      interactions between subtypes and sex were observed with regard to substance use.
      CONCLUSIONS: This study provides evidence showing that subtyping the
      externalizing disorders, ADHD, ODD and CD, along their comorbidity patterns leads
      to important differences regarding substance use. This could have implications
      for the etiology, prevention, and treatment of substance use disorders.

PMID- 24907046
TI  - Predictors of prescribed medication use for depression, anxiety, stress, and
      sleep problems in mid-aged Australian women.
AB  - OBJECTIVE: The study examined prevalence of self-reported use of medication
      recommended or prescribed by a doctor for depression, anxiety, stress, and sleep
      problems; and modelled baseline factors that predicted use over 3 years for each
      condition. METHODS: Analyses were undertaken on the 2001 and 2004 surveys of mid
      aged women in the Australian Longitudinal Study on Women's Health. Dependent
      variables were self-reported use in past 4 weeks of medications recommended or
      prescribed by a doctor for depression, anxiety, stress, or sleep problems in 2001
      and 2004. Generalized Estimating Equations (GEE) were used to predict medication
      use for each condition over 3 years. RESULTS: Prevalence of prescribed medication
      use (2001, 2004) for each condition was depression (7.2, 8.9 %), anxiety (7.4,
      9.0 %), stress (4.8, 5.7 %), and sleep problems (8.7, 9.5 %). Multivariable
      analyses revealed that odds of medication use across 3 years in all four
      conditions were higher for women with poorer mental and physical health, using
      hormone replacement therapy (HRT), or having seen a counsellor; and increased
      over time for depression, anxiety, and stress models. Medication use for
      depression was also higher for overweight/obese women, ex-smokers, and unmarried.
      Medication use for anxiety was higher for unmarried and non-working/low
      occupational women. Medication use for stress was higher for non-working women.
      Additional predictors of medication for sleep were surgical menopause, and area
      of residence. CONCLUSIONS: Self-reported use of prescribed medication for four
      mental health conditions is increased over time after controlling for mental and
      physical health and other variables. Research needs to explore decision-making
      processes influencing differential rates of psychoactive medication use and their
      relationship with health outcomes.

PMID- 24907048
TI  - Desire for information of people with severe mental illness.
AB  - PURPOSE: To assess (1) the desire of people with severe mental illness for
      information on their treatment and (2) whether the desire for information is
      associated with socio-demographic variables, diagnosis, illness duration,
      therapeutic relationship, needs and symptom severity. METHODS: 588 outpatients
      with severe mental illness were recruited in six European countries (Germany,
      Denmark, Hungary, Italy, Switzerland, United Kingdom) during the "Clinical
      decision making and outcome in routine care of people with severe mental illness
      (CEDAR)" study (ISRCTN75841675). Desire for information was assessed by the
      Information subscale of the Clinical Decision Making Style Scale. Study
      participants with high desire for information were compared with those with
      moderate or low desire for information. RESULTS: 80 % of study participants (n =
      462) wanted to receive information on all aspects of their treatment (management,
      prognosis, alternative options for care). Participants with a high desire for
      information had less severe symptoms (OR = 0.988, CI = 0.977-1.000) and a better
      self-rated therapeutic alliance (OR = 1.304, CI = 1.130-1.508) with their
      clinician. CONCLUSIONS: Most, but not all, people with severe mental illness have
      a high desire for information. Desire for information is associated with
      variables, such as therapeutic relationship and symptom severity, which are
      amenable to change during treatment.

PMID- 24907049
TI  - Time-related changes in suicide attempts after the nuclear accident in Fukushima.
AB  - PURPOSE: The aim of this study is to assess whether the risk or types of suicide
      change in Fukushima in the aftermath of a series of disaster, including
      earthquake, tsunami and nuclear accident in March 2011. METHOD: The clinical
      records of all patients visited to the medical centre near the nuclear plant from
      1 year before to 1 year after the disaster were reviewed (n = 981). Patients with
      non-fatal suicide attempt were divided into two categories depending on their
      method of suicide attempt. Standardised mortality ratios were calculated to
      adjust for changes in demographic profiles. RESULTS: The risk of non-fatal
      suicide attempts using high-mortality methods was significantly higher for 4
      months, by three to four times after the series of disasters, and then decreased.
      There was no significant increase of non-fatal suicide attempts using low
      mortality methods after the disaster. CONCLUSIONS: After such a disaster,
      immediate psychiatric support may be required because of the increased risk of
      non-fatal suicide attempts in the immediate aftermath.

PMID- 24907050
TI  - I want what she's having: evidence of human mate copying.
AB  - A variety of non-human females do not select male partners independently. Instead
      they favor males having previous associations with other females, a phenomenon
      known as mate copying. This paper investigates whether humans also exhibit mate
      copying and whether consistent positive information about a man's mate value, and
      a woman's age and self-perceived mate value (SPMV), influence her tendency to
      copy the mate choices of others. Female university students (N = 123) rated the
      desirability of photographed men pictured alone or with one, two, or five women
      represented by silhouettes. In accordance with the visual arrays, men were
      described as currently in a romantic relationship; having previously been in one,
      two, or five relationships; or not having had a romantic relationship in the past
      4 years. Women generally rated men pictured with one or two previous partners as
      more desirable than those with none. Men depicted with five previous partners,
      however, were found to be less desirable. Younger, presumably less experienced
      women had a greater tendency to mate copy compared with older women, but high
      SPMV did not predict greater levels of mate copying. The findings reaffirmed and
      expanded those suggesting that women do not make mate choices independently.

PMID- 24907051
TI  - Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis
      dominates particle shape.
AB  - Several attenuated and non-pathogenic bacterial species have been demonstrated to
      actively target diseased sites and successfully deliver plasmid DNA, proteins and
      other therapeutic agents into mammalian cells. These disease-targeting bacteria
      can be employed for targeted delivery of therapeutic and imaging cargos in the
      form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here
      is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk
      shaped polymeric microparticles. The transport direction for these vehicles can
      be controlled through biased random walk of the attached bacteria in presence of
      chemoattractant gradients in a process known as chemotaxis. In this work, we
      utilize a diffusion-based microfluidic platform to establish steady linear
      concentration gradients of a chemoattractant and investigate the roles of
      chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our
      experimental results demonstrate for the first time that bacterial chemotactic
      response dominates the effect of body shape in extravascular transport; thus, the
      non-spherical system could be more favorable for drug delivery applications owing
      to the known benefits of using non-spherical particles for vascular transport
      (e.g. relatively long circulation time). 

PMID- 24907052
TI  - Microphysical space of a liver sinusoid device enables simplified long-term
      maintenance of chimeric mouse-expanded human hepatocytes.
AB  - While many advanced liver models support hepatic phenotypes necessary for drug
      and disease studies, these models are characterized by intricate features such as
      co-culture with one of more supporting cell types or advanced media perfusion
      systems. These systems have helped elucidate some of the critical biophysical
      features missing from standard well-plate based hepatocyte culture, but their
      advanced designs add to their complexity. Additionally, regardless of the culture
      system, primary hepatocyte culture systems suffer from reproducibility issues due
      to phenotypic variation and expensive, limited supplies of donor lots. Here we
      describe a microfluidic bilayer device that sustains primary human hepatocyte
      phenotypes, including albumin production, factor IX production, cytochrome P450
      3A4 drug metabolism and bile canaliculi formation for at least 14 days in a
      simple monoculture format with static media. Using a variety of channel
      architectures, we describe how primary cell phenotype is promoted by spatial
      confinement within the microfluidic channel, without the need for perfusion or co
      culture. By sourcing human hepatocytes expanded in the Fah, Rag2, and Il2rg
      knockout (FRGTM-KO) humanized mouse model, utilizing a few hundred hepatocytes
      within each channel, and maintaining hepatocyte function for weeks in vitro
      within a relatively simple model, we demonstrate a basic primary human hepatocyte
      culture system that addresses many of the major hurdles in human hepatocyte
      culture research. 

PMID- 24907053
TI  - Dietary trans fatty acids and cardiovascular disease risk: past and present.
AB  - Dietary trans double bond containing fatty acids have been associated with
      increased risk of cardiovascular disease. There are two main sources of dietary
      trans fatty acids: meat and dairy fats, and partially hydrogenated fats. Because
      of a number of factors, including changes in federal labeling requirements for
      packaged foods, and local bans and grassroots pressure on the use of partially
      hydrogenated fat, trans fat intake has declined in recent years. Similar to
      saturated fatty acids, trans fatty acids increase plasma low density lipoprotein
      (LDL)-cholesterol concentrations. In contrast to saturated fatty acids, trans
      fatty acids do not increase high density lipoprotein (HDL)-cholesterol
      concentrations. These differences have been attributed to lipoprotein catabolic
      rate rather than production rate. When reported, effects of partially
      hydrogenated fat on glucose homeostasis, C-reactive protein, blood pressure, and
      LDL oxidation are modest. Although at this time some issues remain unresolved
      regarding trans fatty acids and CVD risk factors other than plasma lipoprotein
      concentrations, they should not affect the final dietary recommendation to limit
      intake. 

PMID- 24907054
TI  - Exercise-induced expression of peroxisome proliferator-activated receptor gamma
      coactivator-1alpha isoforms in skeletal muscle of endurance-trained males.
AB  - The aim of the present study was to investigate the effect of acute aerobic
      exercise on the expression of PGC-1alpha transcript variants in human skeletal
      muscle. Seven endurance-trained athletes performed a 90-min cycling test (62% of
      VO2max). At resting state, the levels of N-truncated (NT)-PGC-1alpha and PGC
      1alpha exon 1a-derived transcripts were significantly higher (>20-fold; P<0.05)
      than those of PGC-1alpha exon 1b- and 1c-derived transcripts. Acute exercise did
      not change the PGC-1alpha exon 1a-derived expression level, but it did increase
      the expression level of NT-PGC-1alpha mRNAs 6-fold, and the expression levels of
      PGC-1alpha exon 1b- and 1c-derived mRNAs>200-fold (P<0.05). We conclude that NT
      PGC-1alpha transcript expression in resting muscle and after acute moderate
      intensity exercise constituted a significant share of total PGC-1alpha
      expression. The exercise led to a higher level of PGC-1alpha expression from
      alternative promoters (exon 1b- and 1c-derived mRNA) than from the canonical
      proximal promoter (exon 1a-derived mRNA).

PMID- 24907055
TI  - Growth of alveoli during postnatal development in humans based on stereological
      estimation.
AB  - Alveolarization in humans and nonhuman primates begins during prenatal
      development. Advances in stereological counting techniques allow accurate
      assessment of alveolar number; however, these techniques have not been applied to
      the developing human lung. Based on the recent American Thoracic Society
      guidelines for stereology, lungs from human autopsies, ages 2 mo to 15 yr, were
      fractionated and isometric uniform randomly sampled to count the number of
      alveoli. The number of alveoli was compared with age, weight, and height as well
      as growth between right and left lungs. The number of alveoli in the human lung
      increased exponentially during the first 2 yr of life but continued to increase
      albeit at a reduced rate through adolescence. Alveolar numbers also correlated
      with the indirect radial alveolar count technique. Growth curves for human
      alveolarization were compared using historical data of nonhuman primates and
      rats. The alveolar growth rate in nonhuman primates was nearly identical to the
      human growth curve. Rats were significantly different, showing a more pronounced
      exponential growth during the first 20 days of life. This evidence indicates that
      the human lung may be more plastic than originally thought, with alveolarization
      occurring well into adolescence. The first 20 days of life in rats implies a
      growth curve that may relate more to prenatal growth in humans. The data suggest
      that nonhuman primates are a better laboratory model for studies of human
      postnatal lung growth than rats. 

PMID- 24907057
TI  - Bakri et al.: is carotid ultrasound necessary in the evaluation of the
      asymptomatic Hollenhorst plaque? (Ophthalmology 2013;120:2747-8).

PMID- 24907056
TI  - Reduced platelet-derived growth factor receptor expression is a primary feature
      of human bronchopulmonary dysplasia.
AB  - Animal studies have shown that platelet-derived growth factor (PDGF) signaling is
      required for normal alveolarization. Changes in PDGF receptor (PDGFR) expression
      in infants with bronchopulmonary dysplasia (BPD), a disease of
      hypoalveolarization, have not been examined. We hypothesized that PDGFR
      expression is reduced in neonatal lung mesenchymal stromal cells (MSCs) from
      infants who develop BPD. MSCs from tracheal aspirates of premature infants
      requiring mechanical ventilation in the first week of life were studied. MSC
      migration was assessed in a Boyden chamber. Human lung tissue was obtained from
      the University of Rochester Neonatal Lung Biorepository. Neonatal mice were
      exposed to air or 75% oxygen for 14 days. PDGFR expression was quantified by
      qPCR, immunoblotting, and stereology. MSCs were isolated from 25 neonates (mean
      gestational age 27.7 wk); 13 developed BPD and 12 did not. MSCs from infants who
      develop BPD showed lower PDGFR-alpha and PDGFR-beta mRNA and protein expression
      and decreased migration to PDGF isoforms. Lungs from infants dying with BPD show
      thickened alveolar walls and paucity of PDGFR-alpha-positive cells in the
      dysmorphic alveolar septa. Similarly, lungs from hyperoxia-exposed neonatal mice
      showed lower expression of PDGFR-alpha and PDGFR-beta, with significant
      reductions in the volume of PDGFR-alpha-positive alveolar tips. In conclusion,
      MSCs from infants who develop BPD hold stable alterations in PDGFR gene
      expression that favor hypoalveolarization. These data demonstrate that defective
      PDGFR signaling is a primary feature of human BPD. 

PMID- 24907058
TI  - Author reply: To PMID 24246827.

PMID- 24907059
TI  - Bilateral lacrimal gland disease: clinical features of 97 cases.
AB  - OBJECTIVE: Bilateral lacrimal gland (LG) disease is a unique presentation that
      can result from varied causes. We reviewed the diagnoses, clinical features, and
      outcomes of 97 patients with this entity. DESIGN: Case series. PARTICIPANTS:
      Ninety-seven patients with bilateral LG disease. METHODS: Retrospective review
      and statistical analysis using analysis of variance and the Fisher exact test.
      MAIN OUTCOME MEASURES: Patient demographics, clinical features, diagnostic
      testing, diagnosis, and treatment. RESULTS: Patient age ranging from 8 to 84
      years (mean, 46 years). The predominant gender was female (77%), and race
      included black (49%), white (38%), and Hispanic (12%) patients. Diagnoses fell
      into 4 categories: inflammatory (n = 51; 53%), structural (n = 20; 21%),
      lymphoproliferative (n = 19; 20%), and uncommon (n = 7; 7%) entities. The most
      common diagnoses included idiopathic orbital inflammation (IOI; n = 29; 30%),
      sarcoidosis (n = 19; 20%), prolapsed LG (n = 15; 15%), lymphoma (n = 11; 11%),
      lymphoid hyperplasia (n = 8; 8%), and dacryops (n = 5; 5%). Inflammatory
      conditions were more likely in younger patients (P<0.05) and in those with pain
      (P<0.001) and mechanical blepharoptosis (P<0.01) at presentation, whereas
      lymphoma was more common in older patients (P<0.001) without active signs of
      inflammation at presentation. Black patients were more likely to have sarcoidosis
      (P<0.01). Laboratory results showed high angiotensin converting enzyme level
      being significantly more likely in patients with sarcoidosis (P<0.05). However,
      sensitivity was limited to 45%, with 25% of patients diagnosed with IOI also
      demonstrating positive results. Corticosteroid therapy was the treatment of
      choice in 38 cases, corresponding to resolution of symptoms in 29% and
      improvement in an additional 32%. Overall, chronic underlying disease was found
      in 71% of patients, among whom 26% achieved a disease-free state, whereas 3%
      succumbed to their underlying disease. CONCLUSIONS: The cause of bilateral
      lacrimal gland disease most commonly was inflammatory, followed by structural and
      lymphoproliferative. Patient characteristics and clinical presentations were key
      features distinguishing between competing possibilities. Despite local control
      with corticosteroids or radiotherapy, underlying disease continued in 71% of
      patients and led to death in 3%.

PMID- 24907060
TI  - Re: Du et al.: incidence of endophthalmitis after corneal transplant or cataract
      surgery in a Medicare population (Ophthalmology 2014;121:290-8).

PMID- 24907061
TI  - Dexamethasone intravitreal implant in the treatment of persistent uveitic macular
      edema in the absence of active inflammation.
AB  - PURPOSE: To examine the observational effectiveness of the dexamethasone (DEX)
      intravitreal implant (Ozurdex; Allergan, Inc., Irvine, CA) in the treatment of
      noninfectious uveitic macular edema in patients with otherwise quiescent uveitis.
      DESIGN: Retrospective chart review. PARTICIPANTS: A total of 27 consecutive
      patients with persistent macular edema resistant to standard short-term therapy
      despite quiescent noninfectious intermediate or posterior uveitis. METHODS: Each
      patient was treated with a DEX 0.7 mg implant. MAIN OUTCOME MEASURES: Primary
      outcome measure was resolution of macular edema 1 month after injection as
      measured by decrease in central macular thickness (CMT). Secondary outcome was
      change in visual acuity 1, 2, and 3 months after injection. RESULTS: A total of
      27 eyes of 27 patients were included for analysis. One eye was randomly selected
      for 6 of these patients who received bilateral DEX implants. There was a
      statistically significant reduction in mean CMT 1 month after DEX implantation
      (mean, 278.9 MUm; range, 206-352 MUm) compared with baseline (mean, 478.7 MUm;
      range, 330-667 MUm) (P < 0.0001). There was a statistically significant
      improvement in visual acuity at 3 months (logarithm of the minimum angle of
      resolution [logMAR] 0.41; 20/51) compared with baseline (logMAR 0.60; 20/80) (P =
      0.0005). There were no major complications after DEX implantation. CONCLUSIONS:
      The DEX implant resulted in a statistically significant improvement in mean CMT
      and visual acuity without any serious adverse events.

PMID- 24907063
TI  - Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study: twelve
      month findings.
AB  - PURPOSE: To report 1-year outcomes of the Prospective Retinal and Optic Nerve
      Vitrectomy Evaluation study. DESIGN: Prospective, controlled, observational
      study. PARTICIPANTS: Eighty eyes of 40 participants undergoing pars plana
      vitrectomy for epiretinal membrane (ERM), macular hole (MH), or vitreous
      opacities. METHODS: Enrolled participants underwent baseline evaluation of the
      study (surgical) and fellow (control) eyes by a masked fellowship-trained
      glaucoma specialist; evaluation included intraocular pressure (IOP; Goldmann
      applanation and Tono-Pen), central corneal thickness, gonioscopy, and cup-to-disc
      ratio measurement. Baseline testing included bilateral color fundus and optic
      disc photography, fundus autofluorescence, automated perimetry, and optical
      coherence tomography (OCT) of the macula and optic nerve. Evaluations were
      repeated at 3 months and 1 year after surgery. MAIN OUTCOME MEASURES: The primary
      outcome measure was changes in peripapillary retinal nerve fiber layer (pRNFL)
      thickness. Secondary outcomes included changes in macular thickness and IOP.
      RESULTS: Thirty-eight of 40 patients completed 1 year of follow-up. Mean visual
      acuity (VA) improved in study eyes from baseline (P = 0.003) but remained worse
      than fellow eyes (P<0.001). Study eyes had thinner inferior pRNFL thickness
      (114+/-16.8 MUm) compared with fellow eyes (123+/-14.7 MUm; P = 0.004). Mean IOP
      difference between study eyes and fellow eyes increased from baseline to 1 year.
      At 1 year, MH study eyes had higher mean IOP (16.0+/-3.7 mmHg) compared with
      fellow eyes (14.8+/-3.4 mmHg; P = 0.08). Mean IOP for pseudophakic study eyes
      increased from 14.5+/-3.2 mmHg at baseline to 16.0+/-2.8 mmHg at 1 year (P =
      0.04). Central subfield thickness (CST) and cube volume decreased in study eyes
      at 1 year but remained greater than that of fellow eyes (P<0.05). Reduction in
      CST from baseline correlated with degree of VA improvement (P<0.05). Mean
      deviation (MD) improved in ERM study eyes at 1 year when compared with baseline (
      2.2 vs. -4.0; P = 0.02) but remained worse than fellow eyes (-1.2; P = 0.002).
      CONCLUSIONS: One year after vitrectomy, VA, CST, and MD improved in study eyes
      but not to the level of fellow eyes. Inferior pRNFL thickness decreased in study
      eyes. Reduction in CST from baseline correlated with degree of VA improvement.
      Pseudophakic study eyes demonstrated increased IOP when compared with baseline.

PMID- 24907065
TI  - Myocardial perfusion defects in scleroderma detected by contrast-enhanced
      cardiovascular magnetic resonance.
AB  - PURPOSE: The authors investigated whether contrast-enhanced cardiovascular
      magnetic resonance (CMR) imaging may be used to detect early cardiac involvement
      in patients with systemic sclerosis (SSc). MATERIALS AND METHODS: Twenty-six SSc
      patients (nine with diffuse cutaneous SSc and 17 with limited cutaneous SSc) and
      13 sex- and age-matched healthy controls (HC) were studied. Contrast-enhanced CMR
      allowed the analysis of first-pass images (areas of hypo-enhancement indicating
      perfusion defects) and delayed images (persistent hyper-enhancement indicating
      fibrosis). Clinical variables including disease duration and presence of major
      visceral complications of SSc were investigated in each patient. RESULTS:
      Perfusion defects were detected in 53.8 % of SSc patients but in none of the HC.
      Perfusion abnormalities were detected in 28.6 % of SSc patients with disease
      duration less than 2 years and in 29.2 % of asymptomatic SSc patients. Delayed
      contrast enhancement was present in 25 % of SSc patients but not in HC. All
      patients with delayed contrast enhancement showed first-pass hypoperfusion. Right
      ventricular wall thickness was significantly increased in all SSc patients when
      compared to HC (p < 0.001); a similar trend was observed when SSc patients
      without pulmonary arterial hypertension were analysed (p < 0.04). A trend to
      lower end-diastolic and end-systolic right ventricular volumes in SSc versus HC
      was observed (p < 0.05 and p < 0.04, respectively). CONCLUSIONS: Myocardial
      hypoperfusion is common in SSc and occurs early in the course of the disease. Co
      localisation of perfusion defects and delayed contrast enhancement indicative of
      fibrosis suggests that myocardial hypoxia may play a role in the pathogenesis of
      myocardial fibrosis.

PMID- 24907062
TI  - Three-year, randomized, sham-controlled trial of dexamethasone intravitreal
      implant in patients with diabetic macular edema.
AB  - PURPOSE: To evaluate the safety and efficacy of dexamethasone intravitreal
      implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with
      diabetic macular edema (DME). DESIGN: Two randomized, multicenter, masked, sham
      controlled, phase III clinical trials with identical protocols were conducted.
      Data were pooled for analysis. PARTICIPANTS: Patients (n = 1048) with DME, best
      corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central
      retinal thickness (CRT) of >=300 MUm by optical coherence tomography. METHODS:
      Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7
      mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months
      for patients treated at month 36) at <=40 scheduled visits. Patients who met
      retreatment eligibility criteria could be retreated no more often than every 6
      months. MAIN OUTCOME MEASURES: The predefined primary efficacy endpoint for the
      United States Food and Drug Administration was achievement of >=15-letter
      improvement in BCVA from baseline at study end. Safety measures included adverse
      events and intraocular pressure (IOP). RESULTS: Mean number of treatments
      received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant
      0.35 mg, and sham, respectively. The percentage of patients with >=15-letter
      improvement in BCVA from baseline at study end was greater with DEX implant 0.7
      mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P <= 0.018). Mean
      average reduction in CRT from baseline was greater with DEX implant 0.7 mg (
      111.6 MUm) and DEX implant 0.35 mg (-107.9 MUm) than sham (-41.9 MUm; P < 0.001).
      Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and
      20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups,
      respectively. Increases in IOP were usually controlled with medication or no
      therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in
      the DEX implant 0.35 mg group required trabeculectomy. CONCLUSIONS: The DEX
      implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in
      BCVA. The safety profile was acceptable and consistent with previous reports.

PMID- 24907066
TI  - The Victorian Lung Cancer Registry pilot: improving the quality of lung cancer
      care through the use of a disease quality registry.
AB  - BACKGROUND: Lung cancer remains a major disease burden in Victoria (Australia)
      and requires a complex and multidisciplinary approach to ensure optimal care and
      outcomes. To date, no uniform mechanism is available to capture standardized
      population-based outcomes and thereby provide benchmarking. The establishment of
      such a data platform is, therefore, a primary requisite to enable description of
      process and outcome in lung cancer care and to drive improvement in the quality
      of care provided to individuals with lung cancer. MATERIALS AND METHODS: A
      disease quality registry pilot has been established to capture prospective data
      on all adult patients with clinical or tissue diagnoses of small cell and non
      small cell lung cancer. Steering and management committees provide clinical
      governance and supervise quality indicator selection. Quality indicators were
      selected following extensive literature review and evaluation of established
      clinical practice guidelines. A minimum dataset has been established and training
      and data capture by data collectors is facilitated using a web-based portal. Case
      ascertainment is established by regular institutional reporting of ICD-10
      discharge coding. Recruitment is optimized by provision of opt-out consent.
      RESULTS: The collection of a standardized minimum data set optimizes capacity for
      harmonized population-based data capture. Data collection has commenced in a
      variety of settings reflecting metropolitan and rural, and public, and private
      health care institutions. The data set provides scope for the construction of a
      risk-adjusted model for outcomes. A data access policy and a mechanism for
      escalation policy for outcome outliers has been established. CONCLUSIONS: The
      Victorian Lung Cancer Registry provides a unique capacity to provide and confirm
      quality assessment in lung cancer and to drive improvement in quality of care
      across multidisciplinary stakeholders.

PMID- 24907068
TI  - Serum albumin, but not glycated albumin was a potent factor affecting the
      performance of GFR equation based on serum creatinine.
AB  - BACKGROUND: Recently, Tsuda et al. reported that high HbA1C or high glycated
      albumin (GA) level is a major factor in overestimation of GFR by Japanese GFR
      equation based on serum creatinine (Eq-cr). They developed a modified equation of
      Eq-cr (M-Eq-cr) using GA or HbA1c. Therefore, effect of GA levels on the
      estimated GFR (eGFR) by Eq-cr was evaluated in Japanese subjects. We validated
      the accuracy of the modified equation using GA by Tsuda et al. (M-Eq-cr) and new
      equations that we developed in the present study. METHODS: Seven hundred and
      fifteen Japanese subjects were included. GFR was measured by inulin renal
      clearance (Cin). The subjects were divided into two groups by upper limit of the
      GA reference range (GA-1: GA < 16.3 % and GA-2: GA > 16.4 %). Factors affecting
      the ratio of eGFR to Cin (eGFR/Cin) were evaluated using multivariate analysis.
      New equations based on creatinine and albumin (Eq-cr-alb) and based on
      creatinine, albumin and GA were developed from development dataset (382
      subjects). Performances of the equations were validated in validation dataset
      (333 subjects). RESULTS: Correlation coefficients between eGFR by Eq-cr and Cin
      were 0.839 and 0.914 in GA-1 and GA-2, respectively. Slopes (95 % confidential
      interval) of the regression lines with zero intercepts were 1.013 (0.991 to
      1.036) and 0.997 (0.951 to 1.043), respectively. Both slopes were not
      significantly different from 1.0. Biases were -2.3 +/- 19.0 and 0.2 +/- 11.7
      ml/min/1.73 m(2), respectively. Accuracy (p30; percentage of subjects within 30 %
      of Cin) (95 % CI) were 78 % (75, 81) and 71 % (62, 78), respectively. There was
      no significant difference in bias and accuracy between the two groups, indicating
      a reasonable accuracy of Eq-cr in GA-1 and GA-2. Multiple regression analysis
      showed that lower serum albumin and higher GA were associated with higher
      eGFR/Cin. Albumin was a more potent factor affecting eGFR/Cin than GA. M-Eq-cr
      significantly underestimated GFR and had significantly larger bias compared with
      Eq-cr in subjects with GA > 20 %, suggesting that the modification of Eq-cr using
      GA by Tsuda et al. was too much compensation in our subjects. Precisions of Eq-cr
      alb were significantly better compared with Eq-cr. CONCLUSION: Eq-cr has a
      reasonable accuracy in GA-1 and GA-2. Lower serum albumin and higher GA were
      significantly associated with higher eGFR/Cin. The former was a more potent
      factor affecting eGFR/Cin. Eq-cr-alb showed better performance compared with Eq
      cr. M-Eq-cr using GA showed too much compensation and did not improve the
      accuracy of the equation in our subjects.

PMID- 24907070
TI  - India is set to miss millennium development goal for improving sanitation.

PMID- 24907067
TI  - Animal models that best reproduce the clinical manifestations of human
      intoxication with organophosphorus compounds.
AB  - The translational capacity of data generated in preclinical toxicological studies
      is contingent upon several factors, including the appropriateness of the animal
      model. The primary objectives of this article are: 1) to analyze the natural
      history of acute and delayed signs and symptoms that develop following an acute
      exposure of humans to organophosphorus (OP) compounds, with an emphasis on nerve
      agents; 2) to identify animal models of the clinical manifestations of human
      exposure to OPs; and 3) to review the mechanisms that contribute to the immediate
      and delayed OP neurotoxicity. As discussed in this study, clinical manifestations
      of an acute exposure of humans to OP compounds can be faithfully reproduced in
      rodents and nonhuman primates. These manifestations include an acute cholinergic
      crisis in addition to signs of neurotoxicity that develop long after the OP
      exposure, particularly chronic neurologic deficits consisting of anxiety-related
      behavior and cognitive deficits, structural brain damage, and increased slow
      electroencephalographic frequencies. Because guinea pigs and nonhuman primates,
      like humans, have low levels of circulating carboxylesterases-the enzymes that
      metabolize and inactivate OP compounds-they stand out as appropriate animal
      models for studies of OP intoxication. These are critical points for the
      development of safe and effective therapeutic interventions against OP poisoning
      because approval of such therapies by the Food and Drug Administration is likely
      to rely on the Animal Efficacy Rule, which allows exclusive use of animal data as
      evidence of the effectiveness of a drug against pathologic conditions that cannot
      be ethically or feasibly tested in humans. 

PMID- 24907069
TI  - Bovine paramphistomes in Ireland.
AB  - Paramphistome infections have been associated with significant morbidity, caused
      chiefly by the activity of juvenile flukes in the intestine of the ruminant final
      host. Most cases have been reported in tropical and sub-tropical areas. However,
      recent reports of an apparent increase in the incidence of rumen fluke and its
      geographical range in Europe have renewed interest in a parasite previously
      thought to be of little significance in temperate regions. Moreover, the identity
      of rumen flukes present in the British Isles is currently being revised. As a
      result, work is underway throughout Europe to review and re-assess the clinical
      and economic significance of rumen flukes. During the present study, historical
      diagnostic laboratory records were interrogated for recent changes in the
      incidence of rumen fluke in Ireland. Three cattle herds were monitored for the
      presence of paramphistome eggs using coprological analysis over a period of 2
      months (in the case of a group of housed steers) and 14 months (in the case of
      two extensively operated farms), respectively. Adult rumen fluke collected
      following slaughter were weighed and typed in two loci. We found that
      Calicophoron daubneyi is the most common if not only paramphistome species
      present in Ireland and that infections in cattle are now much more prevalent than
      was the case five or six years ago. The pylogenetic relationship of our isolates
      to the only published sequence and to C. daubneyi isolates from Northern Ireland
      was analysed. Genetic heterogeneity was similar all over the island and
      comparable to that of Fasciola hepatica, a fact that may have implications for
      the parasite's ability to develop resistance to the very limited number of drugs
      currently available for treatment. The same haplotypes predominated throughout
      the island. Although the clinical significance of C. daubneyi is still uncertain,
      considering the apparent pervasiveness of the parasite, rumen fluke should be
      considered a differential diagnosis when treating scour or ill-thrift in young
      calves, and goats and sheep of any age. 

PMID- 24907071
TI  - Proton beam therapy benefits relatively few cancers, US guideline says.

PMID- 24907072
TI  - US doctors' politics shift left, study shows.

PMID- 24907073
TI  - The impact of chromosomal rearrangements on regulation of gene expression.
AB  - The effects that coding region single-nucleotide polymorphisms or mutations have
      on gene expression have been well documented, predominantly owing to their
      association with disease. The effects of structural chromosomal rearrangements
      are also receiving increasing attention with the development of new techniques
      that allow accurate, high-resolution data, whether genomic interaction or
      transcriptome data, to be generated right down to the single-cell level. Over the
      past 18 months, these advances in experimental techniques have been used to
      further confirm and delineate the substantial effects that chromosome
      rearrangements can have on the regulation of gene expression and provide evidence
      of direct links between the two. 

PMID- 24907074
TI  - Expression QTL-based analyses reveal candidate causal genes and loci across five
      tumor types.
AB  - The majority of trait-associated loci discovered through genome-wide association
      studies are located outside of known protein coding regions. Consequently, it is
      difficult to ascertain the mechanism underlying these variants and to pinpoint
      the causal alleles. Expression quantitative trait loci (eQTLs) provide an
      organizing principle to address both of these issues. eQTLs are genetic loci that
      correlate with RNA transcript levels. Large-scale data sets such as the Cancer
      Genome Atlas (TCGA) provide an ideal opportunity to systematically evaluate eQTLs
      as they have generated multiple data types on hundreds of samples. We evaluated
      the determinants of gene expression (germline variants and somatic copy number
      and methylation) and performed cis-eQTL analyses for mRNA expression and miRNA
      expression in five tumor types (breast, colon, kidney, lung and prostate). We
      next tested 149 known cancer risk loci for eQTL effects, and observed that 42
      (28.2%) were significantly associated with at least one transcript. Lastly, we
      described a fine-mapping strategy for these 42 eQTL target-gene associations
      based on an integrated strategy that combines the eQTL level of significance and
      the regulatory potential as measured by DNaseI hypersensitivity. For each of the
      risk loci, our analyses suggested 1 to 81 candidate causal variants that may be
      prioritized for downstream functional analysis. In summary, our study provided a
      comprehensive landscape of the genetic determinants of gene expression in
      different tumor types and ranked the genes and loci for further functional
      assessment of known cancer risk loci. 

PMID- 24907076
TI  - Single versus double stenting for unprotected left main coronary artery
      bifurcation lesions: a systematic review and meta-analysis.
AB  - OBJECTIVES: We conducted a meta-analysis to assess outcomes for a single-stent
      (SS) strategy versus a double-stent (DS) strategy in treatment of distal
      unprotected left main coronary artery (ULMCA) lesions in the drug-eluting stent
      (DES) era. BACKGROUND: Routine use of DES implantation has contributed to
      improved outcomes in patients undergoing percutaneous coronary intervention (PCI)
      for disease involving the ULMCA. However, PCI for ULMCA bifurcation lesions
      continues to be technically demanding and is an independent predictor of poor
      outcomes. While a number of stenting techniques have been described, the optimal
      strategy remains unknown. METHODS: SS treatment was defined as stenting of the
      main branch alone and DS treatment as stenting of both the main and side
      branches. Our co-primary endpoints were major adverse cardiovascular events
      (MACE), and its individual components. RESULTS: We identified 7 observational
      studies involving 2328 patients. Mean duration of follow-up was 32 months. We
      adopted the random effect model when computing the combined odds ratio (OR).
      There was decreased risk of MACE with SS strategy (20.4%) versus DS strategy
      (32.8%) (OR, 0.51; 95% confidence interval [CI], 0.35-0.73). There was also
      decreased target vessel/target lesion revascularization (TLR/TVR) with SS
      strategy (10.1%) versus DS strategy (24.3%) (OR, 0.35; 95% CI, 0.25-0.49).
      CONCLUSION: Compared to the DS strategy of percutaneous ULMCA bifurcation
      intervention, an SS approach may be associated with better outcomes.

PMID- 24907075
TI  - Association between CLPTM1L polymorphisms (rs402710 and rs401681) and lung cancer
      susceptibility: evidence from 27 case-control studies.
AB  - Genome-wide association studies have identified two SNPs (rs402710 and rs401681)
      of CLPTM1L at chromosome 5p15.33 as a new lung cancer (LC) susceptibility locus
      in populations of European descent. Since then, the relationship between these
      SNPs and LC has been reported in various ethnic groups; however, these studies
      have yielded inconsistent results. To investigate this inconsistency, we
      performed a meta-analysis of 27 studies involving a total of 60,828 cases and
      109,135 controls for the two polymorphisms to evaluate its effect on genetic
      susceptibility for LC. An overall random-effects per-allele odds ratio of 1.14
      (95% CI 1.11-1.16, P < 10(-5)) and 1.15 (95% CI 1.12-1.19, P < 10(-5)) was found
      for the rs401681 and rs402710 polymorphism, respectively. Significant results
      were also observed for under dominant and recessive genetic models. After
      stratified by ethnicity, significant associations were found among Caucasians and
      East Asians. In the subgroup analysis by sample size, significantly increased
      risks were found for these polymorphisms in all genetic models. In addition, we
      find both rs402710 and rs401681 conferred significantly greater risks for
      adenocarcinoma and squamous cell carcinoma when stratified by histological type
      of tumors. Furthermore, associations of these polymorphisms with LC risk were
      observed among current smokers and former smokers, as well as never smokers. Our
      findings demonstrated that rs402710 and rs401681 are risk-conferring factors for
      the development of lung cancer.

PMID- 24907077
TI  - Diabetes mellitus is not a risk factor for coronary artery spasm as assessed by
      an intracoronary acetylcholine provocation test: angiographic and clinical
      characteristics of 986 patients.
AB  - OBJECTIVES: Both diabetes mellitus (DM) and coronary artery spasm (CAS) are
      associated with endothelial dysfunction. Thus, a higher incidence of CAS is
      expected in diabetic patients (pts). We evaluated the impacts of DM and the
      status of blood sugar control on CAS with intracoronary acetylcholine (ACh)
      provocation test. METHODS: A total of 986 pts (106 DM vs 880 non-DM pts) with
      angiographically normal coronary artery received ACh provocation test.
      Significant CAS was defined as a transient >90% luminal narrowing with concurrent
      chest pain and/ or ST-segment changes. HbA1c <7% was considered a controlled
      blood sugar level. RESULTS: The incidence of CAS was similar between patients
      with versus without DM (30.2% vs 23.5%; P=.13). Multivariable analysis showed
      that DM was not an independent risk factor for significant CAS (odds ratio [OR],
      1.29; 95% confidence interval [CI], 0.81-2.07; P=.28). The angiographic
      characteristics of CAS were also similar between these two groups. Subgroup
      analysis regarding the impact of the status of blood sugar control on CAS showed
      that the incidence of CAS was similar between diabetic pts with versus without
      controlled blood sugar levels (35.4% vs 25.9%; P=.29). Multivariable analysis
      showed that the uncontrolled blood sugar level was not an independent risk factor
      for CAS (OR, 0.79; 95% CI, 0.29-2.13; P=.64). CONCLUSIONS: Despite the expected
      endothelial dysfunction, DM and the status of blood sugar control are not
      associated with CAS, suggesting the existence of different mechanisms for CAS and
      coronary artery disease.

PMID- 24907078
TI  - Cardiac catheterization in patients with ascending aortic aneurysms: safety,
      success, and prevalence of coronary artery disease.
AB  - BACKGROUND: Evaluation for coronary artery disease (CAD) is recommended prior to
      surgery for ascending aortic aneurysms. Concerns regarding the use of coronary
      angiography in this population include safety and the ability to successfully
      selectively engage the coronary arteries. Additionally, the prevalence of CAD is
      not well described. METHODS: We retrospectively reviewed all patients referred
      for cardiac catheterization prior to elective surgery for an ascending aortic
      aneurysm at our institution over a 4-year period. Catheter selection was based on
      knowledge of the aneurysm size. Images were screened for whether selective
      coronary engagement was achieved and for the presence of significant coronary
      disease. RESULTS: A total of 205 patients met the inclusion criteria. The mean
      age was 61 years and 63% were male. There were no adverse events related to
      catheterization. The left coronary artery was selectively engaged in 98% of
      patients, and the right coronary in 92%. On average, 3.1 catheters were used for
      angiography per patient. Coronary artery disease was present in 19% of patients
      (n = 39). Increasing age was the only risk factor significantly associated with
      the presence of disease. Coronary bypass was required in 15% of patients at the
      time of aortic aneurysm surgery. CONCLUSIONS: Coronary angiography can be
      performed safely and the coronary arteries can be successfully selectively
      engaged in patients with ascending aortic aneurysms. The findings frequently
      impact the surgical approach. We believe that coronary angiography should be part
      of the routine preoperative evaluation in appropriate patients.

PMID- 24907079
TI  - Transthoracic echocardiography as a measuring and guiding tool for transcatheter
      device closure of secundum atrial septal defect in young children.
AB  - OBJECTIVE: To analyze the effectiveness of transthoracic echocardiography (TTE)
      for device closure of secundum atrial septal defect in children <=5 years old.
      STUDY DESIGN: Quasiexperimental study. STUDY LOCATION AND DURATION: The study was
      conducted at Armed Forces Institute of Cardiology and National Institute of Heart
      Diseases from December 1, 2010 to December 31, 2012. PATIENTS AND METHODS: During
      the study period, a total of 48 children <=5 years old underwent device closure
      of secundum atrial septal defect. The indications for closure were: elective
      closure in 31; parental anxiety in 10; frequent respiratory infection in 4;
      severe pulmonary stenosis in 2; and severe mitral stenosis in 1 patient. The
      procedure was carried out under general or local anesthesia with TTE and
      fluoroscopic guidance. TTE was the primary tool used for measurement of defect
      and estimation of occluder size as well as guiding equipment during device
      deployment in all patients. RESULTS: A total of 47/48 patients (97.9%) had
      successful closure of secundum atrial septal defect. The mean age was 4.1 +/- .68
      years (range, 2.5-5 years) and 28/48 patients (58.4%) were female. The defect
      size and occluders used were between 5-20 mm (mean, 12 +/- 3.5 mm) and 8-22 mm
      (mean, 15 +/- 3.9 mm), respectively. Three patients had simultaneous procedures
      comprising pulmonary balloon valvuloplasty in 2 patients and percutaneous
      transmitral commissurotomy in 1 patient. The device embolization occurred in 1
      patient; the device was retrieved percutaneously and the patient was referred for
      surgical closure. The minor complications were residual leak (n = 1), transient
      bradycardia (n = 4), and first-degree heart block (n = 1). The median procedure
      time was 30 min (range, 15-100 min) and median fluoroscopic time was 6 min
      (range, 1.50-45 min). There were no emergency surgical explorations, cardiac
      perforations, vascular injuries, or deaths during this period. CONCLUSION: TTE
      can be used as a primary tool for the measurement of atrial septal defect and
      guidance during device deployment in young children by skilled and professional
      hands, yet more experience is awaited.

PMID- 24907080
TI  - Novel use of a guide extension mother-and-child catheter for adjunctive
      thrombectomy during percutaneous coronary intervention for acute coronary
      syndromes.
AB  - BACKGROUND: The use of adjunctive thrombectomy during primary percutaneous
      coronary intervention (PCI) has steadily increased with recent trials
      demonstrating an improved clinical and mortality benefit for manual aspiration
      thrombectomy. The use of an in-dwelling guide extension mother-and-child catheter
      allows direct aspiration of thrombus from the vessel with its larger extraction
      area. METHODS: Between December 2011 and September 2013, a total of 17 patients
      who presented with acute coronary syndromes (ACS) in whom a guide extension
      catheter was utilized specifically for manual thrombus aspiration were identified
      and studied. RESULTS: The guide extension catheter was utilized specifically for
      thrombus aspiration in 18 vessels involving 17 patients presenting with ACS where
      severe thrombus burden was noted. The cases involved 4 saphenous vein grafts and
      14 native coronary arteries, with 4 cases involving vessels with late stent
      thrombosis. Successful outcomes with thrombus aspiration and TIMI-3 flow were
      achieved in 17/18 vessels treated, with no adverse outcomes of vessel trauma or
      strokes noted. CONCLUSIONS: Adjunctive manual aspiration thrombectomy utilizing a
      guide extension mother-and-child catheter affords a novel method of thrombus
      aspiration, offering a larger extraction area within the conventional 6 Fr
      system, with demonstrated efficacy for vessel lesions with a large thrombus
      burden.

PMID- 24907081
TI  - Clinical outcome of successful percutaneous coronary intervention for chronic
      total occlusion: results from the multicenter Korean Chronic Total Occlusion (K
      CTO) registry.
AB  - OBJECTIVES: To investigate the impact of the success or failure of chronic total
      occlusion (CTO) interventions on the clinical outcomes in the current drug
      eluting stent (DES) era. BACKGROUND: The impact of the successful CTO
      intervention on long-term clinical outcomes still remains unclear. METHODS:
      Between 2007 and 2009, a total of 2568 patients with CTO were followed in a
      multicenter Korean CTO registry. Of these, successful recanalization with DESs
      occurred in 2045 patients (successful CTO group), whereas failure occurred in 523
      patients (failed CTO group). RESULTS: The occurrence of the composite of cardiac
      death and myocardial infarction (MI) was compared between the successful CTO and
      failed CTO groups. During follow-up (median duration, 729 days), the occurrence
      of cardiac death or MI was significantly lower in the successful CTO group than
      in the failed CTO group (1.7% vs 3.3%; hazard ratio, 0.50; 95% confidence
      interval, 0.28-0.91; P=.02) and the cumulative occurrence in the successful CTO
      group was also significantly lower than in the failed CTO group (1.7% vs 3.0%;
      P=.03) by the Kaplan-Meier method. The successful CTO group had a significantly
      lower need for bypass surgery than the failed CTO group (0.2% vs 2.5%; P<.001).
      In multivariate analysis, procedural success of CTO (odds ratio, 0.51; 95% CI,
      0.29-0.92) was significantly predictive of the occurrence of cardiac death or MI,
      together with age and left ventricular ejection fraction <40%. CONCLUSION: This
      registry study demonstrated that successful CTO intervention with DESs compared
      to failed CTO intervention was associated with lower event rates during follow
      up.

PMID- 24907082
TI  - Developments in coronary chronic total occlusion percutaneous coronary
      interventions: 2014 state-of-the-art update.
AB  - Percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) is a
      rapidly developing field. In the present review, we summarize the most important
      CTO PCI related literature published in 2013. 

PMID- 24907083
TI  - Comparison of resource utilization of pulmonary vein isolation: cryoablation
      versus RF ablation with three-dimensional mapping in the Value PVI Study.
AB  - BACKGROUND: Point-to-point focal radiofrequency (RF) catheter ablation for
      aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is
      the traditional method for treating symptomatic drug-resistant paroxysmal AF
      (PAF) when an ablation procedure is warranted. More recently, pulmonary vein
      isolation (PVI) using the cryoballoon has been demonstrated to be safe and
      effective (STOP AF clinical trial). Currently, two small studies have reviewed
      the procedural efficiency when comparing cryoballoon to focal RF catheter
      ablation procedures; however, no multicenter study has yet reported on this
      comparison of the two types of ablation catheters. METHODS: A multicenter
      retrospective chart extraction and evaluation was conducted at seven
      geographically mixed cardiac care centers. The study examined procedural
      variables during ablation for PVI in PAF patients. RESULTS: In several procedural
      measurements, the two modalities were comparable in efficiencies, including:
      acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30%
      usage of adenosine after procedural testing. However, when compared to RF
      catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory
      occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min
      vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min).
      Additionally, when comparing the material usage of both cryoballoon and RF
      catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc)
      while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac
      echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs
      87%), and fewer transseptal punctures (1.5 vs 1.9). CONCLUSION: This study is the
      first United States multicenter examination to report the procedural comparisons
      between the cryoballoon and focal RF catheters when used for the treatment of PAF
      patients. In this hospital chart review study, potential advantages were found
      when operating the cryoballoon with regard to hospital resource allocation. There
      was no statistical difference between cryoballoon and RF catheters for acute PVI
      success during the ablation procedure.

PMID- 24907084
TI  - Success rate and safety of coronary angiography and angioplasty via radial artery
      approach among a Chinese population.
AB  - OBJECTIVE: To find out the safety and success rate of transradial coronary
      angiography and angioplasty among a Chinese population. DESIGN: This was a
      prospective study performed on 2845 consecutive patients in a single
      interventional center at the first affiliated hospital, Nanjing Medical
      University, in Nanjing from August 2012 to July 2013. Allen's test was carried
      out on all patients who were involved in the study. Patients with abnormal
      Allen's test, cardiogenic shock, those on hemodialysis, and foreigners were
      excluded from the study. Our goal was to determine the efficacy and complications
      of coronary angiography (CAG) and percutaneous coronary intervention (PCI)
      through the radial approach in our local population. RESULTS: The mean age of our
      patients was 64 +/- 7.5 years with 1628 males (57.2%) and 1217 females (42.8%). A
      total of 1537 patients (54.0%) were hypertensive, while 501 patients (17.6%) were
      diabetic. Six patients (0.002%) had previous coronary artery bypass surgery. None
      of our patients had any bleeding disorder. A total of 1416 CAGs (49.8%) and 1429
      PCIs (50.2%) were performed. The success rate was 97.6% for CAG and 96.3% for
      PCI. Seven patients (0.25%) had minor hematoma and 49 patients (1.7%) had reduced
      radial pulse 3-4 hours post procedure. CONCLUSION: Transradial coronary
      intervention is safe and practical. It should be favored over femoral artery as
      an initial access point.

PMID- 24907085
TI  - Evaluating embolic reduction techniques concurrent to infrainguinal
      interventions: a single-center experience.
AB  - OBJECTIVE: To report a single-center retrospective evaluation of embolic
      reduction strategies concurrent to infrainguinal atherectomy intervention.
      METHODS: Fifty-five consecutive atherectomy patients from 2011 to 2012 treated
      with embolic reduction devices were analyzed. Embolic load was stratified by
      lesion type, atherectomy technique, debris capture effectiveness, and risk factor
      characteristics. Over 80% of lesions were complex. Baseline stenosis and average
      lesion length were 94.2 +/- 6.4% and 172.8 +/- 85.5 mm, respectively. Our embolic
      reduction strategy included a systematic approach using the Proteus device in all
      cases and then in combination with the SpiderFX for long or complex lesions.
      Debris was analyzed for count and aggregate surface area. RESULTS: Procedural
      success was 98.2%, with no in-hospital serious adverse events. The mean
      aggregated surface area of captured debris was 22 +/- 20 mm2. Thrombolysis with
      laser produced the highest amount of embolic load followed by laser, directional,
      and orbital atherectomy procedures (P<.05). Patients with restenotic/in-stent
      restenotic lesions produced larger amounts of debris (P<.05). No embolizations
      were recorded up to discharge. Proteus accounted for two-thirds of the debris
      captured in our study; its capture efficiency increased as device and lesion
      length met. An inverse relation was also found between lesion length and embolic
      protection device capture efficacy (TASC-II B vs D; P<.02). CONCLUSION: An
      embolic reduction strategy using the Proteus catheter alone, particularly when
      Proteus and lesion lengths meet, or with the SpiderFX in complex infrainguinal
      atherectomy procedures, can be an effective tool. Current findings suggest
      potential optimization of future "at risk" interventions.

PMID- 24907086
TI  - Coronary artery aneurysms in acute coronary syndrome: case series, review, and
      proposed management strategy.
AB  - Coronary artery aneurysm (CAA) is an uncommon clinical finding, with an incidence
      varying from 1.5%-4.9% in adults, and is usually considered a variant of coronary
      artery disease (CAD). CAA identified in the context of acute coronary syndrome
      (ACS) represents a unique management challenge, particularly if the morphology of
      the CAA is suspected to have provoked the acute clinical syndrome. CAA is
      associated with thrombus formation due to abnormal laminar flow, as well as
      abnormal platelet and endothelial-derived pathophysiologic factors within the
      CAA. Once formed, mural thrombus may potentiate the deposition of additional
      thrombus within aneurysmal segments. Percutaneous revascularization of CAA has
      been associated with complications including distal embolization of thrombus, no
      reflow phenomenon, stent malapposition, dissection, and rupture. Presently, there
      are no formal guidelines to direct the management of CAA in patients presenting
      with ACS; controversies exist whether conservative, surgical, or catheter-based
      management should be pursued. In this manuscript, we present an extensive review
      of the existing literature and associated clinical guidelines, and propose a
      management algorithm for patients with this complex clinical scenario. Armed with
      this perspective, therapeutic decisions may be tailored to synthesize patient
      factors and preferences, individualized clinical assessment, and existing
      American Heart Association/American College of Cardiology guidelines for
      management of ACS. 

PMID- 24907087
TI  - Transfemoral aortic valve-in-valve implantation with the CoreValve Evolut for
      small degenerated stented bioprosthesis.
AB  - Transcatheter aortic valve-in-valve implantation represents one interesting
      therapeutic option for high-risk surgical patients with degenerated
      bioprostheses. The procedure is less invasive and can be performed without
      thoracotomy and general anesthesia, if the femoral approach is used. Until
      recently, failing small bioprostheses could only be treated percutaneously by
      underexpanding the CoreValve (Medtronic, Inc) or Edwards Sapien valve (Edwards
      Lifesciences). Underexpansion of these valves might compromise the hemodynamic
      performance and potentially limit its durability. Herein, we report our initial
      experience with the 23 mm CoreValve Evolut in 4 patients with degenerated 21 mm
      Mitroflow valves. The CoreValve prosthesis was successfully implanted in all 4
      patients, with no major complications and no mortality at 3-month follow-up exam.
      However, 2 of the 4 patients developed mildly elevated transvalvular gradients.
      Therefore, despite our promising results, caution is necessary when considering
      patients with small degenerated bioprostheses for a valve-in-valve procedure. 

PMID- 24907088
TI  - Novel use of an apical-femoral wire rail to assist with transfemoral
      transcatheter aortic valve replacement.
AB  - The inability to reposition or retrieve balloon-expandable transcatheter aortic
      valves once they have been deployed requires implantation of the valve in the
      descending aorta or open surgical procedures to extract the valve. We describe
      the challenging transfemoral delivery of an Edwards Lifesciences Sapien valve
      wherein we had difficulty crossing the aortic valve and the guidewire position
      was compromised. We performed a transapical puncture to snare the guidewire and
      create a left ventricular to femoral wire rail, allowing us to deliver the
      transfemoral transcatheter valve, salvaging a situation where we would have been
      required to implant the valve in the descending aorta. We believe this is the
      first time this technique has been reported and represents an important method to
      facilitate delivery of transcatheter valves where guidewire support is
      insufficient or lost. 

PMID- 24907089
TI  - In-stent anchoring facilitates balloon delivery for final kissing.
AB  - Kissing-balloon inflation has been developed for percutaneous bifurcation
      interventions to improve outcomes and reduced angiographic (re)stenosis. However,
      this procedure is sometimes technically challenging due to inability to deliver
      the side-branch (SB) balloon across the structure of the main vessel stent(s).
      The balloon anchoring technique is reported to enable equipment delivery through
      complex lesions. However, the most important limitation is injury at the site of
      balloon inflation. In this paper, we describe an improved in-stent anchoring
      technique to facilitate balloon delivery to SB and at the same time avoid intimal
      injury. 

PMID- 24907090
TI  - Recanalization of a total occlusion with marked retrograde collateral supply:
      impact of collateral circulation on fractional flow reserve measurements of donor
      artery.
AB  - Fractional flow reserve (FFR)-based coronary interventions of intermediate
      severity lesions are safe, cost effective, and have prognostic importance.
      Although FFR is not affected by heart rate or blood pressure, collateral
      circulation might affect FFR results. Intermediate stenosis at the donor artery
      might be overestimated with FFR measurement due to coronary steal. Moreover, the
      amount of collateral circulation might be a strong determinant of this inaccurate
      measurement. In this report, we present 8 patients who underwent percutaneous
      coronary intervention for totally or subtotally occluded recipient vessels that
      were collateralized by a vessel with intermediate-degree stenosis proximal to the
      separation of the donor side branch evaluated by quantitative coronary
      angiography (QCA). In patients with Rentrop grade-2 or grade-3 collateral flow,
      FFR value of the donor artery was increased at least 0.10 after revascularization
      of the recipient artery. However, FFR value did not change significantly in
      patients with Rentrop grade- 0 or grade-1 collateral flow following
      revascularization. In this case series, we suggest that well-developed collateral
      circulation might result in overestimation of the FFR value in the donor artery
      with mild stenosis. Therefore, in patients undergoing intervention to the
      recipient artery with a well-developed collateral supply and an intermediate
      stenosis at the donor artery, hemodynamic significance of the stenotic lesion
      should be evaluated not only before but also after coronary intervention.
      However, if there is no sufficient collateral circulation to totally occluded
      arteries, FFR values of donor arteries seem to be relatively stable both before
      and after PCI to the recipient artery. 

PMID- 24907091
TI  - Pheochromocytoma found in Takotsubo cardiomyopathy patients.
AB  - Increased level of serum catecholamines in the acute phase was reported to be a
      feature of takotsubo cardiomyopathy (TC). We report a TC case with
      pheochromocytoma, which caused a stir in the diagnosis of TC and suggests the
      importance of screening for a catecholamine-producing tumor. A female patient was
      referred to our emergency department due to ongoing chest pain. Coronary
      angiography showed no abnormality; however, subsequent left ventriculography
      showed basal hyperkinesis and apical ballooning, which completely recovered in 2
      weeks. She experienced significant emotional stress on the eve of her admission,
      to which the diagnosis of TC was attributed. Although serum catecholamine levels
      on admission in our case were higher than on day 14, the value on day 14 was much
      higher than the normal range in our patient. The screening abdominal computed
      tomography scan revealed a left adrenal mass, which was diagnosed as
      pheochromocytoma by 24-hour urinary excretion of catecholamine and (131)I-MIBG
      scintigraphy. The mass was successfully resected and pathological findings
      supported the diagnosis. In our case, emotional stress was thought to be the
      direct trigger to develop TC by exceeding the threshold of catecholamine-induced
      cardiomyopathy. Screening for a catecholamine-producing tumor through careful
      history-taking and measuring catecholamines at a follow-up stage were important
      clinical aspects in this case and may well be for others. 

PMID- 24907092
TI  - Successful percutaneous coronary intervention of chronic total occlusion of the
      right coronary artery using "bidirectional kissing-balloon" technique.
AB  - We report on a 74-year-old man with chronic total occlusion (CTO) of the right
      coronary artery treated with percutaneous coronary intervention using the
      bidirectional kissing-balloon technique. When an antegrade approach fails, a
      retrograde approach to recanalize a CTO is reasonable. However, when the exit of
      the CTO is bifurcated and a protection wire does not advance antegrade into the
      side branch after wire externalization, loss of blood flow after ballooning or
      stenting may result. We report on the usefulness of the bidirectional kissing
      balloon technique for a retrograde approach to chronically totally occluded
      coronary arterial bifurcation lesions. 

PMID- 24907093
TI  - Diagnostic dilemma: Takotsubo cardiomyopathy versus acute coronary syndrome.
AB  - Takotsubo cardiomyopathy is a kind of non-ischemic cardiomyopathy characterized
      by transient apical ballooning of the heart. This often results from sudden,
      temporary weakening of the myocardium. Initially defined in the absence of
      coronary artery disease, it has since expanded to involve patients with coronary
      artery disease. This inclusion is not free of challenges now faced at
      distinguishing between the two when they occur concomitantly, impacting the
      therapeutic interventions. We present a case of takotsubo cardiomyopathy with
      simultaneous coronary artery disease that responded well to conservative
      management and resulted in complete recovery of the patient. This reiterates the
      principle that a case-by-case evaluation of patients with takotsubo
      cardiomyopathy with underlying coronary artery disease needs to be made before an
      individualized therapeutic approach can be taken. 

PMID- 24907094
TI  - Transradial primary percutaneous coronary intervention: a word of caution.

PMID- 24907097
TI  - The impact of education on the perception of facial profile aesthetics and
      treatment need.
AB  - BACKGROUND: The purpose of this study was to evaluate the influence of education
      on the perception of various male and female Caucasian profiles with respect to
      attractiveness and treatment need. METHODS: Four hundred questionnaires were
      distributed among six groups of raters (nonacademic laymen, academic laymen,
      preclinical students, clinical students, orthodontists, and maxillofacial
      surgeons). Male and female profile images were altered digitally in the sagittal
      and vertical dimensions resulting in nine different male and female profiles. The
      raters had to assess the images according to attractiveness and treatment needs.
      RESULTS: Three hundred four questionnaires were completed in this study. Age and
      gender of the rater had no significant influence on the perception of profile
      attractiveness. The different groups of raters perceived the Class I
      normodivergent profiles as most attractive. Significant differences in the
      perception of attractiveness were seen between laymen, orthodontists, and
      maxillofacial surgeons. The orthodontists and maxillofacial surgeons reported
      treatment needs the most. The orthodontists were most sensitive in discerning
      profiles. CONCLUSION: Attractive male and female profiles are recognizable by any
      rater. Education seemed to have a significant influence on facial profile
      perception and recommendation for treatment need of unattractive profiles.
      Professionals should be aware of their judgment discrepancy to laymen. LEVEL OF
      EVIDENCE III: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24907095
TI  - Autistic traits in couple dyads as a predictor of anxiety spectrum symptoms.
AB  - The link between parental autistic tendency and anxiety symptoms was studied in
      491 Taiwanese couples raising biological children with autism spectrum disorders
      (ASDs). Parental autistic tendency as measured by Autism Spectrum Quotient (AQ)
      was associated with anxiety symptoms across all domains. Large effect sizes were
      found in social phobia and post traumatic stress disorders for both parents, and
      in general anxiety disorder and agoraphobia for mothers. These associations were
      irrespective of child's autistic tendency, spouse's AQ scores and the couples'
      compatibility in their autistic tendency. Perceived family support and parental
      education moderated the link but not child's autistic severity. Research and
      clinical implications regarding psychiatric vulnerability of parents of children
      with ASD were drawn and discussed. 

PMID- 24907096
TI  - Does adolescent idiopathic scoliosis relate to vestibular disorders? A systematic
      review.
AB  - Adolescent idiopathic scoliosis (AIS) is a tridimensional deformity of the spinal
      column. This frequent disease, which has no clearly identified pathogenic
      mechanism, can have serious consequences. It has been hypothesized that
      unilateral and isolated vestibular disorders could be the origin of AIS. The
      objective of this work is to verify this hypothesis and to establish a
      pathophysiological model. METHOD: We performed a Pubmed-NCBI search, for the
      period 1966-2013, crossing the keyword scoliosis with the following keywords:
      vestibular, labyrinthine, postural control. RESULTS: This search retrieved 66
      articles. Twenty controlled studies were considered for study. Their analysis
      showed discordant results. This review cannot confirm a link between isolated
      vestibular disorder and occurrence of development of scoliosis. CONCLUSIONS:
      There is not enough evidence to show a link between unilateral, isolated,
      vestibular dysfunction and AIS. From these findings, we propose a more global
      pathophysiological concept, which involves a trouble of the orthostatic postural
      control, with disturbance in the multisensory integration of vestibular, visual
      and somesthesic inputs. AIS could be the consequence of a reorientation of the
      longitudinal body axis in accordance with an erroneous central representation of
      verticality. An assessment of the sense of verticality would allow evaluate this
      hypothesis.

PMID- 24907098
TI  - Selective neurolysis in post-paralytic facial nerve syndrome (PFS).
AB  - Post-paralytic facial nerve syndrome (PFS) summarizes specific symptoms that
      result from an incomplete or poor recovery of the facial nerve after peripheral
      facial palsy. Selective chemodenervation using botulinum toxin A (Btx A) and mime
      therapy represent the therapeutic standard for treating PFS. We report on a 35
      year-old male who was suffering greatly from unilateral PFS-specific movement
      disorders, including periorbital contractions and oculofacial synkinesis that did
      not respond to Btx A administration. We present a surgical alternative to
      overcome periorbital movement disorders by selective neurolysis and review
      therapeutic options for this rare syndrome. In conclusion, selective neurolysis
      appears to be an efficient alternative treatment method of PFS in which the
      quality of life is severely impacted due to movement disorders and there was no
      therapeutic benefit from Btx A. LEVEL OF EVIDENCE V: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors http://www.springer.com/00266 .

PMID- 24907099
TI  - Short-scar facelift without temporal flap: a 10-year experience.
AB  - BACKGROUND: The understanding of facial anatomy and its changes through aging has
      led to the development of several different facelift techniques that focus on
      being less invasive and traumatic and, at the same time, providing natural long
      lasting results. In this article we describe step by step our facelift technique
      as it has been done over the past 10 years by the senior author. METHODS: This is
      a retrospective, descriptive, transversal study in which all patients who
      underwent a rhytidectomy using our technique from January 2002 to September 2012
      were included. All patients were operated on under local anesthesia and
      superficial conscious sedation. All surgeries were performed by the same surgeon.
      A complete step-by-step description of the surgical technique can be found in the
      main article. RESULTS: Between January 2002 and September 2012, a total of 113
      patients underwent facelift surgery. Of these, 88.9 % were women and 11.1 % were
      men. The mean age was 55.3 (+/- 8.66) years. Primary surgeries represented 80.3 %
      (n = 94), secondary 18.8 % (n = 22), and tertiary 0.85 % (n = 1). Only one major
      complication, representing 0.8 %, consisting of a right-sided temporal paresis
      with 2 months complete recovery was seen. The minor complications rate was 23.1
      %. The most common minor complication was hypertrophic/keloid scars which made up
      77.8 % of all minor complications. CONCLUSIONS: The technique described provides
      good and long-lasting aesthetic results with shorter scars, smaller areas of
      dissection (without temporal and postauricular flaps), and a shorter recovery
      period. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors http://www.springer.com/00266 .

PMID- 24907100
TI  - Use of the pectoralis major, serratus anterior, and external oblique fascial flap
      for immediate one-stage breast reconstruction with implant.
AB  - BACKGROUND: Skin- or nipple-sparing mastectomy facilitates immediate one-stage
      reconstruction with an implant. Traditionally, an acellular dermal matrix or a
      muscle flap has been used because the inferolateral portion of the implant cannot
      be covered by the pectoralis major muscle. However, this method has drawbacks,
      including infection, cost, and donor-site morbidity. Therefore, we used an
      autologous conjoined fascial flap composed of the pectoralis major, serratus
      anterior, and external oblique fascia in patients with small-to-medium breasts.
      METHODS: A series of 11 immediate breast reconstructions in 11 patients was
      carried out from March 2010 to June 2011. The conjoined fascial flap and smooth
      round implants were used in all patients. Postoperative photographs were
      evaluated by a blinded panel and scored on a four-point scale. Patient
      satisfaction was evaluated by a postoperative questionnaire that had five items
      designed to evaluate quality of life with the reconstruction. RESULTS: The mean
      body mass index was 23.2 kg/m(2), follow-up period was 30.9 months, and implant
      volume was 286.3 cc. Regarding complications, we observed one case of partial
      skin flap necrosis and one case of seroma accumulation in the axilla, both of
      which healed with conservative care. The mean overall breast satisfaction score
      was 3.18 +/- 0.5. CONCLUSIONS: The conjoined fascial flap is a viable alternative
      for immediate one-stage breast reconstruction with an implant. We recommend
      appropriate patient selection with a body mass index greater than 20 kg/m(2) and
      small-to-medium sized nonptotic breasts. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors http://www.springer.com/00266 .

PMID- 24907101
TI  - Inhibition of oxygen-glucose deprivation-induced apoptosis of human adipose
      derived stem cells by genetic modification with antiapoptotic protein bcl-2.
AB  - BACKGROUND: Adipose-derived stem cells (ADSCs) have become a promising tool for a
      wide range of cell-based therapies. However, transplanted ADSCs do not survive
      well under ischemic conditions. In this study we aimed to inhibit oxygen-glucose
      deprivation (OGD)-induced apoptosis of human ADSCs by genetic modification with
      antiapoptotic protein Bcl-2. METHODS: After isolation and culture, the phenotypes
      of human ADSCs at passage 3 were analyzed by flow cytometry. Then, genetic
      modification of ADSCs with Bcl-2 was carried out. Bcl-2 gene transfection was
      verified by Western blot analysis and multipotent differentiation properties were
      evaluated in Bcl-2-modified ADSCs (Bcl-2-ADSCs). Apoptosis was evaluated by a
      TUNEL assay under ischemic conditions induced by OGD. Apoptotic nuclei were also
      assessed and quantified by Hoechst staining. RESULTS: The cultured ADSCs
      expressed stem cell-associated markers CD29, CD34, CD44, and CD90, but not
      fibroblast marker HLA-DR or hematopoietic stem cell marker CD133. The Bcl-2 gene
      was transferred into ADSCs efficiently, and Bcl-2-ADSCs differentiated into
      adipocytes, chondrocytes, and osteoblasts. In addition, Bcl-2 overexpression
      reduced the percentage of apoptotic Bcl-2-ADSCs by 38 % under OGD. CONCLUSION:
      Our results indicate that Bcl-2 overexpression through gene transfection inhibits
      apoptosis of ADSCs under ischemic conditions. NO LEVEL ASSIGNED: This journal
      requires that authors assign a level of evidence to each submission to which
      Evidence-Based Medicine rankings are applicable. This excludes Review Articles,
      Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver
      Studies, and Experimental Studies. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 24907102
TI  - Nasal splinting: a plaster modification.

PMID- 24907103
TI  - Views of Nigerian gynecologists on the need to establish and implement early
      pregnancy assessment units (EPAUs) in Nigerian hospitals.

PMID- 24907104
TI  - Pediatric emotion dysregulation: biological and developmental evidence for a
      dimensional approach.
AB  - The following review article examines the value of a dimensional approach to
      research in relation to recent findings of child and adolescent emotion
      dysregulation. With the publication of the DSM-5, it is important to keep in mind
      that difficulties in pinpointing causal mechanisms may result from the collective
      grouping of different emotional deficits by diagnoses. Evidence available from
      studies examining pediatric emotion dysregulation indicate strengths in the
      dimensional approach for research, especially in light of developmental changes
      to neural activations of emotion regulation. Use of a dimensional approach in
      research appears to be an effective tactic that could pave the way for a better
      understanding of pediatric emotion dysregulation and thereby elucidate better
      treatments and outcomes for those with this behavioral deficit, regardless of
      diagnosis. 

PMID- 24907105
TI  - [Neuroepigenetics: Desoxyribonucleic acid methylation in Alzheimer's disease and
      other dementias].
AB  - DNA methylation is an epigenetic mechanism that controls gene expression. In
      Alzheimer's disease (AD), global DNA hypomethylation of neurons has been
      described in the human cerebral cortex. Moreover, several variants in the
      methylation pattern of candidate genes have been identified in brain tissue when
      comparing AD patients and controls. Specifically, DNA methylation changes have
      been observed in PSEN1 and APOE, both genes previously being involved in the
      pathophysiology of AD. In other degenerative dementias, methylation variants have
      also been described in key genes, such as hypomethylation of the SNCA gene in
      Parkinson's disease and dementia with Lewy bodies or hypermethylation of the GRN
      gene promoter in frontotemporal dementia. The finding of aberrant DNA methylation
      patterns shared by brain tissue and peripheral blood opens the door to use those
      variants as epigenetic biomarkers in the diagnosis of neurodegenerative diseases.

PMID- 24907106
TI  - [Labial tumefaction].

PMID- 24907107
TI  - [Arrhythmia and muscular exercise intolerance revealing lamin genetic defect in a
      young adult].
AB  - INTRODUCTION: Arrhythmic disorders are infrequent in young adult and should evoke
      myopathy associated cardiomyopathy, even though muscular symptoms are moderate or
      absent. CASE REPORT: We report a 25-year-old woman who developed severe
      supraventricular rhythm disturbances with exercise intolerance and elevated serum
      creatine kinase level. Initially the echocardiography showed normal ventricular
      function. Mutation in the lamin gene (LMNA) was identified. During the disease
      course, arrhythmia and ventricular function worsened and required cardioverter
      defibrillator implantation. CONCLUSION: Laminopathies are genetic disorders among
      which dilated cardiomyopathy associated with skeletal muscular involvement is the
      most frequent phenotype, usually like Emery-Dreifuss muscular dystrophy. Other
      phenotypes are progeria, lipodystrophic syndromes and peripheral neuropathy.
      Cardiac involvement is responsible for syncope, thromboembolic events and sudden
      death and often requires early cardioverter defibrillator implantation.

PMID- 24907108
TI  - [Inflammasomes in human diseases].
AB  - The understanding of the innate immunity, the first line of the host defence, was
      significantly modified following the sequential discovery of innate immune
      receptors such as the Toll-like receptors (TLRs) and the NOD-like receptors
      (NLRs). In response to recognition of microbial patterns or danger signals, some
      NLRs assemble a multimolecular platform termed as the inflammasome. Inflammasome
      assembly leads to the activation of the proinflammatory caspase-1. Consequently,
      an inflammatory immune response is mounted along with a programmed cell death,
      called pyroptosis. This review summarizes recent advances in the knowledge of the
      inflammasome and its role in auto-inflammatory diseases, autoimmune diseases, and
      most common metabolic, cardiovascular or rheumatic diseases. 

PMID- 24907109
TI  - [Bing-Neel syndrome: Report of 4 cases and literature review].
AB  - INTRODUCTION: Neurological manifestations during Waldenstrom disease are common
      and are usually related to immune peripheral neuropathy or serum hyperviscosity
      syndrome. The infiltration of the central nervous system by the
      lymphoproliferative syndrome is known as the Bing-Neel syndrome. This extremely
      rare entity remains poorly described in the literature. CASE REPORTS: We report
      on 4 cases of patients for whom central neurological disorders led to the
      diagnosis of a Bing and Neel syndrome. These four cases illustrate different
      clinical presentations, diagnosis, therapeutic options, and outcome in this
      syndrome. Based on our literature review, we discuss about these differences.
      CONCLUSION: The polymorphic clinical manifestations of Bing and Neel syndrome can
      mimic many diagnoses. However, it may be necessary to consider this diagnosis.
      Cerebrospinal fluid analysis and MRI may allow rapid diagnosis or guide a biopsy.
      Prolonged remissions are possible with appropriate treatment.

PMID- 24907110
TI  - Postnatal development of Blake's pouch cyst: a case report and new insight for
      its pathogenesis.
AB  - Blake's pouch cyst (BPC), a rare cystic malformation in the posterior fossa, is
      believed to be caused by the congenital expansion of the posterior membranous
      area that normally regresses during embryogenesis. However, due to the wide
      spectrum of the onset pattern and age of patients, the natural history and the
      pathogenesis are poorly understood. The authors describe the case of a girl who
      admitted with headache and right abducens nerve paresis at the age of 3 years and
      10 months. Magnetic resonance (MR) imaging demonstrated a tetraventricular
      hydrocephalus, an open aqueduct, and a posterior fossa cyst compatible with BPC.
      Multiple tumors were also noticed in the ventricular wall. Tumor biopsy and an
      endoscopic third ventriculostomy were performed. Intraoperative observation
      confirmed the BPC, and pathological diagnosis was pilomyxoid astrocytoma. In
      retrospect, MR imaging was performed twice in the past, at the age of 8 months
      and again at 22 months, and no anomaly was detected, suggesting that Blake's
      pouch was once regressed. Therefore, a BPC in this patient was certainly
      developed after her second or third year of life. The ventricular tumors may
      influence the cerebrospinal fluid (CSF) absorption, which triggered the re
      expansion of BPC from the possible remnant of Blake's pouch. This is a rare but
      important report providing evidence that in addition to the classic congenital
      BPC in which the remnant of Blake's pouch remains persistent, there could be
      postnatal or secondary BPC, which develops after birth. Possible mechanisms
      include that the remnant of Blake's pouch, which originally disappears, may re
      expand postnatally in association with unknown trigger or a change in CSF
      dynamics or absorption. 

PMID- 24907111
TI  - Intracranial germinomas in a father and his son.
AB  - BACKGROUND: Primary intracranial germ cell tumors (IGCTs) represent an uncommon
      category of neoplasms, and familial occurrence is rare. We present the first
      report of parent-child patients with pathologically confirmed pure germinomas.
      CASE REPORT: A 36-year-old Japanese man presented with diabetes insipidus and
      hypopituitarism. Magnetic resonance imaging (MRI) revealed a mass lesion in the
      pituitary stalk, which was diagnosed as a pure germinoma by open craniotomy tumor
      biopsy. Seven years later, his 13-year-old son also presented with diabetes
      insipidus. MRI revealed mass lesions in the pituitary stalk and the pineal
      region. He underwent endoscopic tumor biopsy for the pineal lesion, which was
      diagnosed as a pure germinoma. Both the father and his son were treated with
      combined radiochemotherapeutic regimens and achieved complete remission after one
      to two cycles of chemotherapy. CONCLUSION: Although there have been three
      previous case reports of familial germinoma, all of these involved sibling pairs.
      The present report represents the first parent-child cases. This type of familial
      occurrence suggests the possibility that germline mutations may also be involved
      in the development of IGCTs.

PMID- 24907112
TI  - Molecular pathways: the basis for rational combination using MEK inhibitors in
      KRAS-mutant cancers.
AB  - Mutations in RAS oncogenes are frequently observed in human cancers, and the
      mutations result in activation of the RAS-RAF-MEK-ERK pathway, leading to cell
      proliferation and survival. The pathway is, therefore, a potent therapeutic
      target in the RAS-mutant cancers. MEK inhibitors can specifically block the
      pathway and are one of the key types of drugs for the treatment of the RAS-mutant
      cancers. As RAS proteins activate other downstream signaling proteins in addition
      to the RAS-RAF-MEK-ERK pathway, combination therapeutic approaches with MEK
      inhibitors are also being evaluated. Moreover, MEK inhibitors can arrest cancer
      cells in G1 phase and repress prosurvival Bcl2 family proteins such as MCL1 and
      BCL2/BCLXL, and increase expression of Bim, a proapoptotic BH3-only family
      protein. This mechanism may explain the efficacy of the combination of MEK
      inhibitors with cytotoxic agents or other targeted inhibitors. A better
      understanding of the pathway will help us with development of rational
      combinations for the treatment of the RAS-mutant cancers.

PMID- 24907113
TI  - Inhibition of tumor-derived prostaglandin-e2 blocks the induction of myeloid
      derived suppressor cells and recovers natural killer cell activity.
AB  - PURPOSE: Increased frequencies of myeloid-derived suppressor cells (MDSC)
      correlate with poor prognosis in patients with cancers. Tumor-derived
      prostaglandin-E2 (PGE2) plays an important role in inducing MDSCs. However, the
      detailed mechanisms of this induction remain unknown. To develop targeted
      therapies for MDSCs, we sought to investigate the molecular basis of PGE2
      regulated accumulation of MDSCs and their functional consequence on natural
      killer (NK) cell activity. EXPERIMENTAL DESIGN: The effects of PGE2 in inducing
      phenotypic, signaling, and functional alternations on monocytes were analyzed in
      vitro. Suppression of NK-cell activity by PGE2-treated monocytes was compared
      with that of freshly isolated CD14(+)HLA-DR(low/-) monocytic MDSCs (moMDSC) from
      patients with melanoma. In addition, to explore the in vivo relevance of
      targeting PGE2 to reduce MDSC-mediated suppression of NK cells, we established a
      murine model, where tumor cells were disabled from cyclooxygenase-2 (COX-2)
      production. RESULTS: Patient-derived moMDSCs inhibited NK-cell activity through
      the production of TGFbeta. In vitro, binding of PGE2 to EP2 and EP4 receptors on
      monocytes activated the p38MAPK/ERK pathway and resulted in elevated secretion of
      TGFbeta. Similar to moMDSCs, PGE2-treated monocytes potently suppressed NK-cell
      activity through production of TGFbeta. Furthermore, silencing COX-2 in murine
      4T1 tumor cells reduced the accumulation of CD11b(+)Gr1(+) MDSCs in the spleen,
      resulting in concomitant improved in vivo clearance of NK-cell sensitive YAC-1
      cells. CONCLUSIONS: Our results reveal an indispensable role of tumor-derived
      PGE2 in inducing MDSCs and suggest a favorable outcome of combining COX-2
      targeted therapy and adoptive NK-cell transfer in patients with cancer.

PMID- 24907114
TI  - Polymorphisms of asparaginase pathway and asparaginase-related complications in
      children with acute lymphoblastic leukemia.
AB  - PURPOSE: Asparaginase (ASNase) is a standard and critical component in the
      therapy of childhood acute lymphoblastic leukemia (ALL), but it is also
      associated with several toxicities. EXPERIMENTAL DESIGN: We recently reported the
      results of an association study between ASNase pathway genes and event-free
      survival (EFS) in childhood patients with ALL. The same polymorphisms were
      interrogated here in relation to allergies, pancreatitis, and thrombotic events
      following treatment with E. coli ASNase. RESULTS: Among patients of the discovery
      group, allergies, and pancreatitis were more frequent in individuals who are
      homozygous for the triple-repeat allele (3R) of the asparagine synthetase (ASNS)
      gene, resulting in remarkably higher risk of these toxicities associated with
      3R3R genotype [OR for allergies, 14.6; 95% confidence interval (CI), 3.6-58.7; P
      < 0.0005 and OR for pancreatitis, 8.6; 95% CI, 2.0-37.3; P = 0.01]. In contrast,
      the ASNS haplotype *1 harboring double-repeat (2R) allele had protective effect
      against these adverse reactions (P <= 0.01). The same haplotype was previously
      reported to confer reduction in EFS. The risk effect of 3R3R genotype was not
      replicated in the validation cohort, whereas the protective effect of haplotype
      *1 against allergies was maintained (P <= 0.002). Analysis with additional
      polymorphisms in ASNS locus in lymphoblastoid cell lines showed that haplotype *1
      is diversified in several subtypes of which one was associated with reduced in
      vitro sensitivity to ASNase (rs10486009, P = 0.01) possibly explaining an
      association seen in clinical setting. CONCLUSIONS: This finding might have
      implication for treatment individualization in ALL and other cancers using
      asparagine depletion strategies. Clin Cancer Res; 21(2); 329-34. (c)2014 AACR.
      See related commentary by Avramis, p. 230.

PMID- 24907116
TI  - Identification and characterization of a ligand-selective mineralocorticoid
      receptor coactivator.
AB  - The mineralocorticoid receptor (MR) is unique in responding to 2 physiological
      ligands: aldosterone and cortisol. In epithelial tissues, aldosterone selectivity
      is determined by the activity of 11beta-hydroxysteroid dehydrogenase type 2. In
      other tissues, cortisol is the primary ligand. To understand the structural
      determinants of ligand-specific MR activation, we sought to identify coregulatory
      molecules that interact with the ligand-binding domain (LBD) of the MR. A yeast-2
      hybrid (Y2H) kidney cDNA library was screened with the human MR-LBD in the
      presence of aldosterone and cortisol. One clone, identified as aldosterone
      specific in the Y2H assay, exhibited a 7-fold greater response, aldosterone vs.
      cortisol, in a mammalian-2-hybrid (M2H) assay. This clone encodes the region of
      the tesmin gene that has 2 leucine-x-x-leucine-leucine (LxxLL) motifs. Full
      length tesmin coactivates (>2-fold) MR-mediated transactivation in the presence
      of aldosterone, but not of cortisol; this specificity is observed with a range of
      promoters. GST pulldown and coimmunoprecipitation of the MR by tesmin supports a
      direct interaction, mediated by the 2 LxxLL motifs. Tesmin thus represents a
      novel MR coregulator that exhibits a differential interaction, providing further
      evidence of the adoption of ligand-dependent conformations by the MR-LBD.

PMID- 24907115
TI  - Essential role of aldehyde dehydrogenase 1A3 for the maintenance of non-small
      cell lung cancer stem cells is associated with the STAT3 pathway.
AB  - PURPOSE: Lung cancer stem cells (CSC) with elevated aldehyde dehydrogenase (ALDH)
      activity are self-renewing, clonogenic, and tumorigenic. The purpose of our study
      is to elucidate the mechanisms by which lung CSCs are regulated. EXPERIMENTAL
      DESIGN: A genome-wide gene expression analysis was performed to identify genes
      differentially expressed in the ALDH(+) versus ALDH -: cells. RT-PCR, Western
      blot analysis, and Aldefluor assay were used to validate identified genes. To
      explore the function in CSCs, we manipulated their expression followed by colony
      and tumor formation assays. RESULTS: We identified a subset of genes that were
      differentially expressed in common in ALDH(+) cells, among which ALDH1A3 was the
      most upregulated gene in ALDH(+) versus ALDH -: cells. shRNA-mediated knockdown
      of ALDH1A3 in non-small cell lung cancer (NSCLC) resulted in a dramatic reduction
      in ALDH activity, clonogenicity, and tumorigenicity, indicating that ALDH1A3 is
      required for tumorigenic properties. In contrast, overexpression of ALDH1A3 by
      itself it was not sufficient to increase tumorigenicity. The ALDH(+) cells also
      expressed more activated STAT3 than ALDH -: cells. Inhibition of STAT3 or its
      activator EZH2 genetically or pharmacologically diminished the level of ALDH(+)
      cells and clonogenicity. Unexpectedly, ALDH1A3 was highly expressed in female,
      never smokers, well-differentiated tumors, or adenocarcinoma. ALDH1A3 low
      expression was associated with poor overall survival. CONCLUSIONS: Our data show
      that ALDH1A3 is the predominant ALDH isozyme responsible for ALDH activity and
      tumorigenicity in most NSCLCs, and that inhibiting either ALDH1A3 or the STAT3
      pathway are potential therapeutic strategies to eliminate the ALDH(+)
      subpopulation in NSCLCs.

PMID- 24907117
TI  - Umbilical vein catheter tip - slight rightward or anterior shift and trajectory
      can indicate liver penetration.

PMID- 24907118
TI  - Crosstalk between TGF-beta1 and CXCR3 signaling during urethral fibrosis.
AB  - Urethral fibrosis is an important pathological feature of urethral stricture. TGF
      beta1 and CXC chemokine receptor 3 (CXCR3) signaling have been reported as the
      critical pathways involved in the pathology of fibrosis. Here, we collected the
      urine samples from the patients with recurring urethral stricture, recurring
      stricture treated by cystostomy, and age- and gender-matched healthy people.
      ELISA detection revealed that TGF-beta1 level was significantly up-regulated for
      the urethral stricture patients. By contrast, flow cytometry, real-time PCR
      detection, and immunofluoresecent staining showed that urethral stricture
      resulted in decreased expression of CXCR3. TGF-beta1 treatment could increase
      cell proliferation and migration ability of urethra fibroblasts, whereas IP
      10/CXCR3 signaling showed the opposite effect. Further, we found a crosstalk
      between TGF-beta1 and CXCR3 signaling in the regulation of urethral fibrosis.
      Thus, pharmacological intervention of TGF-beta1 or CXCR3 signaling has a
      potential as the therapeutic target for the prevention of urethral fibrosis. 

PMID- 24907119
TI  - Long-term temporal tracking of speech rate affects spoken-word recognition.
AB  - Humans unconsciously track a wide array of distributional characteristics in
      their sensory environment. Recent research in spoken-language processing has
      demonstrated that the speech rate surrounding a target region within an utterance
      influences which words, and how many words, listeners hear later in that
      utterance. On the basis of hypotheses that listeners track timing information in
      speech over long timescales, we investigated the possibility that the perception
      of words is sensitive to speech rate over such a timescale (e.g., an extended
      conversation). Results demonstrated that listeners tracked variation in the
      overall pace of speech over an extended duration (analogous to that of a
      conversation that listeners might have outside the lab) and that this global
      speech rate influenced which words listeners reported hearing. The effects of
      speech rate became stronger over time. Our findings are consistent with the
      hypothesis that neural entrainment by speech occurs on multiple timescales, some
      lasting more than an hour. 

PMID- 24907120
TI  - Knowledge About Hospice Care and Beliefs About Pain Management: Exploring
      Differences Between Hispanics and Non-Hispanics.
AB  - CONTEXT: Among Hispanics, incomplete knowledge about hospice care may explain low
      rates of utilization and culturally-specific beliefs about pain and pain
      treatments may contribute to disparities in pain management. OBJECTIVES: To
      compare (1) knowledge and attitudes regarding hospice, (2) and beliefs about pain
      and pain medication between Hispanics and non-Hispanics. METHODS: A cross
      sectional phone-based survey of adults living in the contiguous United States was
      conducted using randomly selected phone numbers with over-sampling for diversity.
      Measures assessed knowledge (a 23-item test), attitudes (an 8-item scale),
      experiences, preferences related to hospice and beliefs regarding pain and pain
      management. RESULTS: 123 individuals participated in the survey, 13% of whom were
      Hispanic. Hispanics were less likely to have heard of hospice are (p <. 001) and,
      among those who had, more likely to have inaccurate information about it (p =
      .05). Specifically, Hispanics were more likely to report that only individuals
      over age 65 are eligible for hospice services, which is incorrect (44% vs. 93% of
      non-Hispanics; p=.001). Only 67% of Hispanics knew that hospice helps family
      members as well as the dying person. More Hispanics (43%) than non-Hispanics
      (9.3%) reported that admitting pain is a sign of weakness (p < .001). A greater
      proportion of Hispanic respondents agreed that a good patient does not talk about
      pain (p = .07): 38% vs. 18% from non-Hispanics. CONCLUSION: Despite the
      increasing knowledge of hospice care among Hispanics, specific information about
      the scope of services remains limited. Cultural beliefs about pain management,
      along with inadequate knowledge of the role of pain management at end of life,
      persist.

PMID- 24907121
TI  - The Cost of Inappropriate Care at the End of life: Implications for an Aging
      Population.
AB  - Elderly patients patients (older than 65 years) account for only 11% of the US
      population yet they account for 34% of health care expenditure. The
      disproportionate usage of health care costs by elderly patients is in striking
      contrast with that of other Western Nations. It is likely that these differences
      are largely due to variances in hospitalization and the use of high technology
      health care resources at the end of life. The United States has 8 times as many
      intensive care unit (ICU) beds per capita when compared to other Western Nations.
      In the United States, elderly patients currently account for 42% to 52% of ICU
      admissions and for almost 60% of all ICU days. A disproportionate number of these
      ICU days are spent by elderly patients before their death. In many instances,
      aggressive life supportive measures serve only to prolong the patient's death.
      Such treatment inflicts pain and suffering on the patient (with little prospects
      of gain) and incurs enormous financial costs to the health care system. We
      present the case of an 86-year-old female who spent almost 3 months in our ICU
      prior to her death. The fully allocated hospital costs for this patient were
      estimated to be US$254 945 (US$5100/d). With the increasing age of the population
      and the projected increased demand for ICU beds, we review the benefits and
      burdens of admitting elderly patients to the ICU. 

PMID- 24907122
TI  - Changes in and Associations Among Functional Status and Perceived Quality of Life
      of Patients With Metastatic/Locally Advanced Cancer Receiving Rehabilitation for
      General Disability.
AB  - The primary aims were to clarify the changes in the functional status and quality
      of life of patients with metastatic/locally advanced cancer who received
      rehabilitation therapy. This is a cohort study, and all consecutive patients who
      received rehabilitation therapy were evaluated before and 2 weeks after. Outcome
      measures were the Functional Independence Measure (FIM), perceived independence,
      and overall quality of life (European Organization for Research and Treatment of
      Cancer C30). A total of 128 patients were included. Although the FIM score
      significantly decreased, the overall quality of life significantly increased.
      Even in the patients with deteriorated FIM scores, the overall quality of life
      was maintained despite a significantly decreased perceived independence.
      Terminally ill patients with cancer who received a rehabilitation program
      maintained their overall quality of life despite an objective decline in the
      physical functional status. 

PMID- 24907123
TI  - Strategies for Development of Palliative Care From the Perspectives of General
      Population and Health Care Professionals: A Japanese Outreach Palliative Care
      Trial of Integrated Regional Model Study.
AB  - This study primarily aimed to identify future actions required to promote
      palliative care in Japan. The future actions regarded as effective by the general
      population were "improve physicians' skill in palliative care" (61%), "create a
      counseling center for cancer" (61%), and "improve nurses' skill in palliative
      care" (60%). In contrast, future actions regarded as effective by the health care
      professionals were "set up a Web site that provides information about cancer"
      (72%), "promote consultation with specialists in palliative care" (71%), and
      "open an outpatient department specializing in palliative care" (70%). The
      results suggest (1) development and maintenance of settings; (2) enhancement of
      palliative care education and training programs for health care providers; and
      (3) improvement in distributing information about cancer and regional palliative
      care resources to the general population. 

PMID- 24907124
TI  - Pharmacotherapy for weight loss.

PMID- 24907125
TI  - Factors associated with the donation and non-donation of embryos for research: a
      systematic review.
AB  - BACKGROUND: Systematic knowledge on the factors that influence the decisions of
      IVF users regarding embryo donation for research is a core need for patient
      centred policies and ethics in clinical practice. However, no systematic review
      has been provided on the motivations of patients who must decide embryo
      disposition. This paper fills this gap, presenting a systematic review of
      quantitative and qualitative studies, which synthesizes the current body of
      knowledge on the factors and reasons associated with IVF patients' decisions to
      donate or not to donate embryos for research. METHODS: A systematic search of
      studies indexed in PubMed, ISI WoK and PsycINFO, published before November 2013,
      was conducted. Only empirical, peer-reviewed, full-length, original studies
      reporting data on factors and reasons associated with the decision concerning
      donation or non-donation of embryos for research were included. Eligibility and
      data extraction were performed by two independent researchers and disagreements
      were resolved by discussion or a third reviewer, if required. The main
      quantitative findings were extracted and synthesized and qualitative data were
      assessed by thematic content analysis. RESULTS: A total of 39 studies met the
      inclusion criteria and were included in the review. More than half of the studies
      (n = 21) used a quantitative methodology, and the remaining were qualitative (n =
      15) or mixed-methods (n = 3) studies. The studies were derived mainly from
      European countries (n = 18) and the USA (n = 11). The proportion of IVF users who
      donated embryos for research varied from 7% in a study in France to 73% in a
      Swiss study. Those who donate embryos for research reported feelings of
      reciprocity towards science and medicine, positive views of research and high
      levels of trust in the medical system. They described their decision as better
      than the destruction of embryos and as an opportunity to help others or to
      improve health and IVF treatments. The perception of risks, the lack of
      information concerning research projects and the medical system and the
      conceptualization of embryos in terms of personhood were the most relevant
      motives for not donating embryos for research. Results relating to the influence
      of sociodemographic characteristics and reproductive and gynaecological history
      were mostly inconclusive. CONCLUSIONS: Three iterative and dynamic dimensions of
      the IVF patients' decision to donate or not to donate embryos for research
      emerged from this review: the hierarquization of the possible options regarding
      embryo disposition, according to the moral, social and instrumental status
      attributed to embryos; patients' understanding of expectations and risks of the
      research on human embryos; and patients' experiences of information exchange and
      levels of trust in the medical-scientific institutions.

PMID- 24907126
TI  - Niemann-Pick Disease Type C: Induced Pluripotent Stem Cell-Derived Neuronal Cells
      for Modeling Neural Disease and Evaluating Drug Efficacy.
AB  - Niemann-Pick disease type C (NPC) is a rare neurodegenerative disorder caused by
      recessive mutations in the NPC1 or NPC2 gene that result in lysosomal
      accumulation of unesterified cholesterol in patient cells. Patient fibroblasts
      have been used for evaluation of compound efficacy, although neuronal
      degeneration is the hallmark of NPC disease. Here, we report the application of
      human NPC1 neural stem cells as a cell-based disease model to evaluate nine
      compounds that have been reported to be efficacious in the NPC1 fibroblasts and
      mouse models. These cells are differentiated from NPC1 induced pluripotent stem
      cells and exhibit a phenotype of lysosomal cholesterol accumulation. Treatment of
      these cells with hydroxypropyl-beta-cyclodextrin, methyl-beta-cyclodextrin, and
      delta-tocopherol significantly ameliorated the lysosomal cholesterol
      accumulation. Combined treatment with cyclodextrin and delta-tocopherol shows an
      additive or synergistic effect that otherwise requires 10-fold higher
      concentration of cyclodextrin alone. In addition, we found that hydroxypropyl
      beta-cyclodextrin is much more potent and efficacious in the NPC1 neural stem
      cells compared to the NPC1 fibroblasts. Miglustat, suberoylanilide hydroxamic
      acid, curcumin, lovastatin, pravastatin, and rapamycin did not, however, have
      significant effects in these cells. The results demonstrate that patient-derived
      NPC1 neural stem cells can be used as a model system for evaluation of drug
      efficacy and study of disease pathogenesis.

PMID- 24907127
TI  - Biomechanical study of expandable pedicle screw fixation in severe osteoporotic
      bone comparing with conventional and cement-augmented pedicle screws.
AB  - Pedicle screws are widely utilized to treat the unstable thoracolumbar spine. The
      superior biomechanical strength of pedicle screws could increase fusion rates and
      provide accurate corrections of complex deformities. However, osteoporosis and
      revision cases of pedicle screw substantially reduce screw holding strength and
      cause loosening. Pedicle screw fixation becomes a challenge for spine surgeons in
      those scenarios. The purpose of this study was to determine if an expandable
      pedicle screw design could be used to improve biomechanical fixation in
      osteoporotic bone. Axial mechanical pull-out test was performed on the
      expandable, conventional and augmented pedicle screws placed in a commercial
      synthetic bone block which mimicked a human bone with severe osteoporosis.
      Results revealed that the pull-out strength and failure energy of expandable
      pedicle screws were similar with conventional pedicle screws augmented with bone
      cement by 2 ml. The pull-out strength was 5-fold greater than conventional
      pedicle screws and the failure energy was about 2-fold greater. Besides, the pull
      out strength of expandable screw was reinforced by the expandable mechanism
      without cement augmentation, indicated that the risks of cement leakage from
      vertebral body would potentially be avoided. Comparing with the biomechanical
      performances of conventional screw with or without cement augmentation, the
      expandable screws are recommended to be applied for the osteoporotic vertebrae.

PMID- 24907128
TI  - Prediction of structural failure of tibial bone models under physiological loads:
      effect of CT density-modulus relationships.
AB  - Although finite element (FE) models can provide distinct benefits in
      understanding knee biomechanics, in particular the response of the knee to
      implants, their usefulness is limited by the modelling assumptions and input
      parameters. This study highlights the uncertainty of material input parameters
      derived from the literature and its limitation on the accuracy and usefulness of
      FE models of the tibia. An FE model of the intact human knee and a database of
      knee forces (muscles, ligaments and medial and lateral tibio-femoral contacts)
      were developed for walking and stair-descent activities. Ten models were
      constructed from ten different combinations of apparent bone density to elastic
      modulus material property relationships, published in the literature. Some of the
      published material property relationships led to predictions of bone strains in
      the proximal tibia which exceeded published failure criteria under loads imposed
      by normal activities. These relationships appear not to be applicable for the
      human tibia. There is a large discrepancy in proposed relationships that cover
      the cancellous bone density range. For FE models of the human tibia, the material
      relationship proposed by Morgan et al., which assumed species and anatomic site
      dependence, produced the most believable results for cancellous bone. In addition
      to casting doubt on the use of some of the published density-modulus
      relationships for analysis of the human proximal tibia, this study highlights the
      need for further experimental work to characterise the behaviour of bone with
      intermediate densities. 

PMID- 24907129
TI  - In vivo application of an optical segment tracking approach for bone loading
      regimes recording in humans: a reliability study.
AB  - This paper demonstrates an optical segment tracking (OST) approach for assessing
      the in vivo bone loading regimes in humans. The relative movement between retro
      reflective marker clusters affixed to the tibia cortex by bone screws was tracked
      and expressed as tibia loading regimes in terms of segment deformation. Stable in
      vivo fixation of bone screws was tested by assessing the resonance frequency of
      the screw-marker structure and the relative marker position changes after hopping
      and jumping. Tibia deformation was recorded during squatting exercises to
      demonstrate the reliability of the OST approach. Results indicated that the
      resonance frequencies remain unchanged prior to and after all exercises. The
      changes of Cardan angle between marker clusters induced by the exercises were
      rather minor, maximally 0.06 degrees . The reproducibility of the deformation
      angles during squatting remained small (0.04 degrees /m-0.65 degrees /m). Most
      importantly, all surgical and testing procedures were well tolerated. The OST
      method promises to bring more insights of the mechanical loading acting on bone
      than in the past. 

PMID- 24907130
TI  - Medium-term outcome of Astra Tech implants in head and neck oncology patients.
AB  - Rehabilitation with implant-retained prostheses is a key step in the
      rehabilitation of patients after ablative head and neck surgery. Data of patients
      who underwent mandibular restoration with Astra Tech implants were gathered
      consecutively and analyzed retrospectively. Implant survival was calculated by
      Kaplan-Meier analysis, and Cox models were used to identify any association
      between implant failure and contributing factors. In total, 136 implants were
      placed in 33 patients. The main reason for ablative surgery was squamous cell
      carcinoma. Twenty-one patients received adjuvant radiotherapy with a cumulative
      radiation dose of 56-76Gy prior to implantation. Failure occurred in six
      patients, resulting in the loss of 17 implants. The cumulative implant survival
      rate was 92.7% after 1 year and 87.5% after 20 months. Smoking and alcohol
      consumption were associated with a significantly higher implant failure rate.
      Most patients had a stable implant status after 20 months. 

PMID- 24907131
TI  - Two cases of posterior open bite caused by the thickness of retrodiscal tissue in
      the temporomandibular joint.
AB  - There have been few reports of mouth closing disturbances in the final phase of
      occlusion caused by the posterior thickness of the retrodiscal tissue. Two such
      cases are described here. The first was a 70-year-old female suffering from a
      painless mouth closing disturbance on the right side of the temporomandibular
      joint (TMJ). She complained of a feeling like there was an air cushion. The
      second case was a 51-year-old male with a painless mouth closing disturbance on
      the left side of the TMJ. In both cases, magnetic resonance imaging (MRI)
      revealed enlargement of the posterior joint space on the affected side. The
      conditions of these two cases were improved by local injection of steroid
      preparations; however further additional treatments were required, including
      mandible traction in one case and dental prosthetics in the other. Consequently,
      we consider that the local injection of steroid preparations is useful as an
      initial treatment, while the use of local injection of steroid preparations alone
      is not sufficient for the treatment of posterior thickness of the retrodiscal
      tissue. 

PMID- 24907132
TI  - Promoting positive attitudes of tobacco-dependent mental health patients towards
      NRT-supported harm reduction and smoking cessation.

PMID- 24907133
TI  - 'From blood to blood': de-differentiation of hematopoietic progenitors to stem
      cells.

PMID- 24907134
TI  - Relative Risk of Deep Vein Thrombosis in Very Elderly Patients Compared With
      Elderly Patients.
AB  - Deep vein thrombosis (DVT) and pulmonary embolism are major causes of morbidity
      and mortality in patients during hospitalization; previous studies have proposed
      that an advanced age of more than 60 years is a risk factor for these conditions.
      This study analyzes the relative risk of DVT in very elderly patients older than
      90 years of age compared with elderly patients aged 80 to 89 years. The study was
      performed at the Department of Internal Medicine, University Hospital of
      Saarland, Homburg/Saar, Germany, between 2004 and 2012. After completing
      ultrasound examinations, 20 (64.52%, 12 [60%] female patients, mean age 91.8 +/-
      1.83 years) of the 31 patients in the study group and 132 (62.26%, 87 [65.91%]
      female patients, mean age 83.84 +/- 2.66 years) of the 212 patients in the
      control group were diagnosed with DVT. An increased relative risk of DVT was not
      discovered in the very elderly patients (relative risk, 1.04; P = .80). 

PMID- 24907135
TI  - Protein Z G79A polymorphism and puerperal cerebral venous thrombosis.
AB  - Protein Z (PZ), a cofactor for PZ-dependent protease inhibitor, is known to play
      an important role in inhibiting the coagulation cascade. The aim of the study was
      to investigate whether PZ G79A polymorphism is a risk factor for puerperal
      cerebral venous thrombosis (CVT). A total of 71 patients with puerperal CVT and
      98 healthy controls were genotyped for PZ 79GA polymorphism by polymerase chain
      reaction-restriction fragment length polymorphism method. In patients, the
      genotype distribution for GG, GA, and AA genotypes was 22.5%, 43.7%, and 33.8%,
      and in controls, 25.5%, 40.8%, and 33.7%, respectively. The risk associated with
      carrying the mutant genotype (GA and AA) versus the wild GG genotype was found to
      be 1.11 (95% confidence interval: 0.52-2.35; P = .909). There was no significant
      difference in the clinical features of the patients with and without the
      polymorphism. We therefore conclude that PZ G79A polymorphism is not a risk
      factor for puerperal CVT in Indian women. 

PMID- 24907136
TI  - Promoting leisure participation as part of health and well-being in children and
      youth with cerebral palsy.
AB  - Participation in leisure is a human right and is central to the health of
      children and youth. The World Health Organization's International Classification
      of Functioning, Disability and Health for Children and Youth supported a change
      in thinking about what outcomes are most relevant in the context of children's
      health and places participation as one of the constituent elements of health.
      Participation is also a fundamental rehabilitation and health promotion outcome
      for children with cerebral palsy as identified by youth, parents, and health
      professionals. Several studies have identified individual and environmental
      factors related to participation in leisure; new studies are now determining the
      best interventions to promote participation. This article summarizes recent
      findings and proposes important topics for neurologists to consider in exploring
      leisure pursuits with children with cerebral palsy and their families and in
      working with rehabilitation professionals to promote engagement in leisure
      opportunities as part of integrated care. 

PMID- 24907137
TI  - Pediatric aquatic therapy on motor function and enjoyment in children diagnosed
      with cerebral palsy of various motor severities.
AB  - This study investigates the effects of pediatric aquatic therapy on motor
      function, enjoyment, activities of daily living, and health-related quality of
      life for children with spastic cerebral palsy of various motor severities.
      Children with spastic cerebral palsy were assigned to a pediatric aquatic therapy
      group (n = 11; mean age = 85.0 +/- 33.1 months; male : female = 4 : 7) or a
      control group (n = 13; mean age = 87.6 +/- 34.0 months; male : female = 9 : 4).
      The statistic results indicate that the pediatric aquatic therapy group had
      greater average 66-item Gross Motor Function Measure following intervention than
      the control group (eta(2) = 0.308, P = .007), even for children with Gross Motor
      Function Classification System level IV (5.0 vs 1.3). The pediatric aquatic
      therapy group had higher Physical Activity Enjoyment Scale scores than the
      control group at post-treatment (P = .015). These findings demonstrate that
      pediatric aquatic therapy can be an effective and alternative therapy for
      children with cerebral palsy even with poor Gross Motor Function Classification
      System level. 

PMID- 24907138
TI  - Spontaneous involution of diffuse fibrous dysplasia of paranasal sinuses.
AB  - We report the case of a 25-year-old patient, diagnosed at age 10, with diffuse
      fibrous dysplasia of the paranasal sinuses, an extremely rare idiopathic
      condition. This diagnosis is possible only by cerebral computed tomography (CT),
      cerebral and anterior skull base magnetic resonance imaging (MRI), and
      histopathology. Surgical treatment is common. This boy had mild symptoms:
      moderate headache in the morning that did not affect his daily activity, and
      rhinitis, partially responsive to medication. The neurologic examination was
      abnormal. Radiographs, CT, and MRI showed a diffuse mass in the paranasal sinuses
      which had a histopathological diagnosis of fibrous dysplasias. The family refused
      to refer the patient to surgery. The boy has been monitored annually for 15
      years. He has remained asymptomatic without headache since age 11, with normal,
      general and neurologic examinations. Serial MRIs showed a spontaneous partial
      involution of the mass. 

PMID- 24907139
TI  - Late-onset epileptic spasms: clinical evidence and outcome in 34 patients.
AB  - To evaluate the diverse presentation and course of late-onset epileptic spasms in
      relation to etiology, we analyzed the clinical, electroencephalographic (EEG),
      and prognostic features in 34 patients. We divided the patient sample into
      cryptogenic or symptomatic based on etiology. An association emerged between
      symmetric spasms at onset and focal interictal EEG abnormalities in cryptogenic
      patients, and onset with focal or generalized seizures before displaying
      asymmetric spasms, and multifocal or diffuse EEG abnormalities, in the
      symptomatic group. Despite an overall poor prognosis, symptomatic patients
      starting with generalized seizures seem to have a relatively more favorable
      outcome. The high occurrence of intellectual disability, and sometimes
      psychomotor regression, confirmed this rare and poorly understood heterogeneous
      clinical condition as a severe form of epileptic encephalopathy that deserves
      further study. 

PMID- 24907140
TI  - Coxofemoral joint kinematics using video fluoroscopic images of treadmill-walking
      cats: development of a technique to assess osteoarthritis-associated disability.
AB  - The objectives of this pilot study were to develop a video fluoroscopy kinematics
      method for the assessment of the coxofemoral joint in cats with and without
      osteoarthritis (OA)-associated disability. Two non-OA cats and four cats affected
      by coxofemoral OA were evaluated by video fluoroscopy. Video fluoroscopic images
      of the coxofemoral joints were captured at 120 frames/s using a customized C-arm
      X-ray system while cats walked freely on a treadmill at 0.4 m/s. The angle
      patterns over time of the coxofemoral joints were extracted using a graphic user
      interface following four steps: (i) correction for image distortion; (ii) image
      denoising and contrast enhancement; (iii) frame-to-frame anatomical marker
      identification; and (iv) statistical gait analysis. Reliability analysis was
      performed. The cats with OA presented greater intra-subject stride and gait cycle
      variability. Three cats with OA presented a left-right asymmetry in the range of
      movement of the coxofemoral joint angle in the sagittal plane (two with no
      overlap of the 95% confidence interval, and one with only a slight overlap)
      consistent with their painful OA joint, and a longer gait cycle duration.
      Reliability analysis revealed an absolute variation in the coxofemoral joint
      angle of 2o-6o, indicating that the two-dimensional video fluoroscopy technique
      provided reliable data. Improvement of this method is recommended: variability
      would likely be reduced if a larger field of view could be recorded, allowing the
      identification and tracking of each femoral axis, rather than the trochanter
      landmarks. The range of movement of the coxofemoral joint has the potential to be
      an objective marker of OA-associated disability. 

PMID- 24907141
TI  - A conjugative plasmid carrying the carbapenem resistance gene blaOXA-23 in AbaR4
      in an extensively resistant GC1 Acinetobacter baumannii isolate.
AB  - OBJECTIVES: To locate the acquired bla(OXA-23) carbapenem resistance gene in an
      Australian A. baumannii global clone 1 (GC1) isolate. METHODS: The genome of the
      extensively antibiotic-resistant GC1 isolate A85 harbouring bla(OXA-23) in Tn2006
      was sequenced using Illumina HiSeq, and the reads were used to generate a de novo
      assembly. PCR was used to assemble relevant contigs. Sequences were compared with
      ones in GenBank. Conjugation experiments were conducted. RESULTS: The sporadic
      GC1 isolate A85, recovered in 2003, was extensively resistant, exhibiting
      resistance to imipenem, meropenem and ticarcillin/clavulanate, to cephalosporins
      and fluoroquinolones and to the older antibiotics gentamicin, kanamycin and
      neomycin, sulfamethoxazole, trimethoprim and tetracycline. Genes for resistance
      to older antibiotics are in the chromosome, in an AbaR3 resistance island. A
      second copy of the ampC gene in Tn6168 confers cephalosporin resistance and the
      gyrA and parC genes have mutations leading to fluoroquinolone resistance. An 86
      335 bp repAci6 plasmid, pA85-3, carrying bla(OXA-23) in Tn2006 in AbaR4, was
      shown to transfer imipenem, meropenem and ticarcillin/clavulanate resistance into
      a susceptible recipient. A85 also contains two small cryptic plasmids of 2.7 and
      8.7 kb. A85 is sequence type ST126 (Oxford scheme) and carries a novel KL15
      capsule locus and the OCL3 outer core locus. CONCLUSIONS: A85 represents a new
      GC1 lineage identified by the novel capsule locus but retains AbaR3 carrying
      genes for resistance to older antibiotics. Resistance to imipenem, meropenem and
      ticarcillin/clavulanate has been introduced into A85 by pA85-3, a repAci6
      conjugative plasmid carrying Tn2006 in AbaR4.

PMID- 24907143
TI  - Evaluation of concomitant methylphenidate and opioid use in patients with pain.
AB  - Methylphenidate is a central nervous system simulant that is used for management
      of opioid-induced sedation. Sparse data exist regarding use patterns of
      methylphenidate and opioids in patients with pain. This retrospective data
      analysis evaluated concomitant methylphenidate and opioid use from physician
      reported medication lists and in urine specimens of patients with pain. All
      specimens were analyzed and quantified with LC-MS-MS. Concomitant methylphenidate
      and opioid use (e.g., sample population) were compared with a baseline population
      of patients taking opioids. There were 3,326 patients with physician-reported use
      of methylphenidate. Of these, 1,089 patients were tested for the presence of
      methylphenidate in urine. Methylphenidate was positive in urine for 551 patients
      (detection rate of 50.6%). Ritalinic acid was positive in 776 patients (detection
      rate of 71.3%). The current study observed differences in the use pattern of
      methylphenidate based on opioid type. Physician-reported use revealed methadone
      had the highest percent difference between the sample and baseline populations
      (77%, P <= 0.05). Fentanyl, morphine and hydromorphone also had higher percent
      differences of 19.6, 25.3 and 32.3%, respectively. Further studies need to
      examine the apparent discrepancies between the physician-reported medication
      lists and urine drug testing of concomitant methylphenidate and opioid use in
      patients with pain. 

PMID- 24907142
TI  - Switching from tenofovir/emtricitabine and nevirapine to a
      tenofovir/emtricitabine/rilpivirine single-tablet regimen in virologically
      suppressed, HIV-1-infected subjects.
AB  - OBJECTIVES: Nevirapine is an inducer of hepatic metabolism. After
      discontinuation, nevirapine has an inductive effect on cytochrome P450 3A4, which
      persists for a few weeks and which, after switching to rilpivirine, may reduce
      rilpivirine exposures and have a negative clinical impact. This study evaluates
      the virological outcome, pharmacokinetics and safety of switching virologically
      suppressed, HIV-1-infected patients from nevirapine to rilpivirine. PATIENTS AND
      METHODS: This 24 week open-label single-centre study included HIV-1-infected
      adults with HIV-1 RNA <50 copies/mL for >6 months on tenofovir/emtricitabine and
      nevirapine, who were willing to simplify their regimen to
      tenofovir/emtricitabine/rilpivirine. Virological suppression, safety and
      nevirapine and rilpivirine pharmacokinetics were assessed. RESULTS: At weeks 12
      and 24, all 32 subjects remained virologically suppressed. One subject
      discontinued at week 1 for rilpivirine-associated insomnia and two patients chose
      to resume tenofovir/emtricitabine and nevirapine after week 12 because of
      rilpivirine-associated food constraint. There was no grade 3/4 laboratory
      abnormality. Rilpivirine trough concentrations were above the mean trough
      concentrations observed in Phase 3 studies by 1 week post-switch. Twenty-seven
      out of 32 patients had no measurable levels of nevirapine by 2 weeks post-switch.
      The meal accompanying tenofovir/emtricitabine/rilpivirine intake satisfied food
      requirements in 81% of cases. Overall general satisfaction was improved in 90% of
      the subjects despite food constraints. CONCLUSION: Nevirapine has a short and
      limited inductive effect on rilpivirine metabolism, which is not clinically
      significant. Tenofovir/emtricitabine/rilpivirine is an efficacious and safe
      option for virologically suppressed HIV-infected patients on nevirapine wishing
      to simplify their regimen.

PMID- 24907144
TI  - Synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment
      of type 2 leprosy reactions.
AB  - We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular
      hybridization and evaluated their potential for the treatment of type 2 leprosy
      reactions. All of the compounds had analgesic properties. Compounds 3c and 3h
      were the most active antinociceptive compounds and reduced acetic acid-induced
      abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds
      also reduced tumor necrosis factor-alpha levels in lipopolysaccharide-stimulated
      L929 cells. Compound 3i was the most active compound; at concentrations of 15.62
      and 125 MUM, compound 3i decreased tumor necrosis factor-alpha levels by 86.33%
      and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in
      vivo, compound 3i did not reduce the number of bacilli compared with controls.
      Compound 3i did not have mutagenic effects in Salmonella typhimurium strains
      TA100 and TA102, with or without metabolic activation (S9 mixture). Our results
      indicate that compound 3i is a novel lead compound for the treatment of type 2
      leprosy reactions.

PMID- 24907145
TI  - Preparation and biological evaluation of 1'-cyano-2'-C-methyl pyrimidine
      nucleosides as HCV NS5B polymerase inhibitors.
AB  - The first synthesis of 1'-cyano-2'-C-methyl pyrimidine nucleosides is described.
      Anti-HCV activity of these nucleosides and their nucleotide phosphoramidate
      prodrugs was assessed and compared to the 1'-unsubstituted counterparts and to
      the related 1'-cyano-2'-C-methyl C-nucleoside parent of GS-6620. 

PMID- 24907146
TI  - Further occurrences of Dohrniphora cornuta (Bigot) (Diptera, Phoridae) in
      forensic cases indicate likely importance of this species in future cases.
AB  - Dohrniphora cornuta (Bigot), an oriental species of scuttle fly, has been
      transported around the world by man. We report it from forensic cases in England,
      Spain and Sweden. It is likely to feature in forensic cases elsewhere in the
      world. 

PMID- 24907147
TI  - Short-term efficacy of etanercept plus methotrexate vs combinations of disease
      modifying anti-rheumatic drugs with methotrexate in established rheumatoid
      arthritis.
AB  - OBJECTIVES: The aims of this study were to investigate the short-term benefit of
      etanercept (ETN) + MTX vs conventional synthetic DMARDs (csDMARDs; HCQ, LEF or
      SSZ) + MTX in subjects with established RA. The effect of disease duration (<=2
      years vs >2 years) and severity (moderate vs severe) on treatment outcomes was
      also assessed. Methods. Data from Asian and Latin American subjects with
      inadequate response to MTX were pooled from the APPEAL (ETN 25 mg biweekly + MTX
      or csDMARD + MTX; NCT00422227) and Latin RA (ETN 50 mg/week + MTX or csDMARD +
      MTX; NCT00848354) studies. Endpoints included the 28-joint DAS with ESR (DAS28
      ESR) low disease activity (LDA; <=3.2), DAS28 remission (<2.6) and HAQ score
      <=0.5. RESULTS: Four hundred seventy-eight subjects received ETN + MTX, 245
      subjects received csDMARD + MTX [HCQ + MTX (n = 81), LEF + MTX (n = 69), SSZ +
      MTX (n = 95)]. At week 16, significantly more subjects receiving ETN + MTX vs
      subjects on csDMARDs + MTX achieved DAS28-ESR LDA (39% vs 18%, P < 0.001),
      remission (18% vs 7%, P < 0.001) and HAQ <=0.5 (48% vs 34%, P < 0.001). For both
      treatment arms, these endpoints were achieved by a greater proportion of subjects
      with <=2 years vs >2 years disease duration and with moderate vs severe disease
      activity. CONCLUSION: Overall, ETN + MTX was more effective in treating subjects
      with established RA than csDMARDs + MTX at 16 weeks. More subjects with shorter
      disease duration and moderate disease activity achieved optimal response
      regardless of treatment regimen. TRIAL REGISTRATION: clinicaltrials.gov,
      NCT00422227 and NCT00848354.

PMID- 24907148
TI  - Ultrasonography as an additional item in the American College of Rheumatology
      classification of Sjogren's syndrome.
AB  - OBJECTIVE: In this study we evaluated US as an additional classification item in
      the ACR classification of SS. METHODS: Of 581 patients classified as either SS (n
      = 364) or non-SS (n = 217) based on the minimum requirements of the American
      European Consensus Group (AECG) classification, 184 patients (102 SS and 82 non
      SS) who had scored two or more positive or two or more negative results according
      to the ACR criteria were selected. The AECG classification was used as the gold
      standard. A parotid and/or submandibular gland that was assigned a score >=G1 was
      designated as SS positive. We evaluated US alone or with varying combinations of
      the ACR classification items in the diagnosis of SS. RESULTS: The ACR criteria
      diagnosed the 184 patients with 91% sensitivity, 90% specificity and 91%
      accuracy. US alone diagnosed the 184 ACR patients with 79% sensitivity, 90%
      specificity and 83% accuracy, which was comparable to the results of US diagnosis
      in the AECG cohort (81%, 86% and 83%, respectively). Incorporating the US
      criteria as an alternative to one of the three ACR classification items achieved
      89-91% sensitivity, 87-96% specificity and 89% or 92% accuracy, which was
      comparable to that of the original ACR classification. Furthermore, kappa
      analysis indicated that the results of the original ACR and US-replaced ACR
      classifications matched completely (kappa = 0.960-0.974). CONCLUSION: These
      results suggest that US can be used as an alternative to any of the three ACR
      classification items.

PMID- 24907150
TI  - Steroid-resistant remitting seronegative symmetrical synovitis with pitting
      oedema associated with gout treated with etanercept.

PMID- 24907151
TI  - Identification of relapse predictors in IgG4-related disease using multivariate
      analysis of clinical data at the first visit and initial treatment.
AB  - OBJECTIVES: Inducting clinical remission by glucocorticoid treatment is
      relatively easy in IgG4-related disease (IgG4-RD), but relapse also occurs easily
      with tapering of the steroid dose. The present study tried to analyse the cases
      to extract predictors of relapse present at the diagnosis of IgG4-RD. METHODS:
      Subjects comprised 79 patients with IgG4-related dacryoadenitis and sialadenitis,
      known as Mikulicz's disease, who were diagnosed between April 1997 and October
      2013 and followed-up for >2 years from the initial induction treatment. They were
      applied to Cox proportional hazard modelling, based on the outcome of interval to
      relapse. We performed multivariate analysis for the clinical factors of these
      cases and identified predictors of relapse. RESULTS: Identified factors were male
      sex and younger onset in cases without organ involvement at diagnosis and low
      levels of serum IgG4 in cases with organ dysfunction at diagnosis. Complication
      with autoimmune pancreatitis and low steroid dose at initial treatment also
      tended to be associated with recurrence. CONCLUSION: Follow-up is important in
      cases with recognized risk factors for relapse, including male sex and younger
      onset in cases without organ damage.

PMID- 24907152
TI  - A longitudinal study of ankle brachial pressure indices in a cohort of patients
      with systemic sclerosis.
AB  - OBJECTIVES: Digital ischaemia, often progressing beyond RP to digital ulceration
      and sometimes even gangrene, is the most common vascular manifestation of SSc.
      Both microvascular and macrovascular disease can contribute and coexistence of
      microvascular and macrovascular (proximal vessel) disease in patients with SSc is
      potentially limb threatening. The aims of this study were to examine the change
      over time in the ankle brachial pressure index (ABPI) in a cohort of patients
      with SSc and to examine whether age, gender, smoking status, disease duration,
      disease subtype and ACA are associated with ABPI. METHODS: The clinical and
      laboratory data of 217 patients attending the SSc clinic at a tertiary referral
      centre and who had their ABPIs checked between 1996 and 2011 were reviewed
      retrospectively. Data were analysed to see how the ABPI changed with time and
      linear mixed effects modelling was used to determine which factors were
      associated with ABPI. RESULTS: In most patients with SSc, the ABPI remained
      constant over time [median rate of change 0 units/year, interquartile range (IQR)
      -0.01-0.01]. There was a significant association between lower ABPI and
      increasing age (P = 0.04), the limited cutaneous subtype of SSc (P = 0.01) and
      ACA positivity (P = 0.03). Additionally there was an association between ABPI and
      smoking status of borderline statistical significance (P = 0.08). CONCLUSION:
      This study provides further evidence for associations between the severity of
      vascular disease in patients with SSc and increasing age, smoking, limited
      cutaneous disease and positive ACA. Reassuringly, in most patients ABPI remains
      stable over time.

PMID- 24907149
TI  - Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding
      of the pivotal role of inflammation, risk predictors and the impact of treatment.
AB  - Risk of cardiovascular (CV) disease is increased among RA patients. High
      inflammatory burden associated with RA appears to be a key driver of the
      increased cardiovascular risk. Inflammation is linked with accelerated
      atherosclerosis and associated with a paradoxical inversion of the relationship
      between CV risk and lipid levels in patients with untreated RA, recently coined
      the lipid paradox. Furthermore, the inflammatory burden is also associated with
      qualitative as well as quantitative changes in lipoproteins, with the anti
      inflammatory and atheroprotective roles associated with high-density lipoprotein
      cholesterol significantly altered. RA therapies can increase lipid levels, which
      may reflect the normalization of lipids due to their inflammatory-dampening
      effects. However, these confounding influences of inflammation and RA therapies
      on lipid profiles pose challenges for assessing CV risk in RA patients and
      interpretation of traditional CV risk scores. In this review we examine the
      relationship between the increased inflammatory burden in RA and CV risk,
      exploring how inflammation influences lipid profiles, the impact of RA therapies
      and strategies for identifying and monitoring CV risk in RA patients aimed at
      improving CV outcomes. 

PMID- 24907153
TI  - Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory
      cytokines and bone loss in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to describe the associations between serum
      levels of 25-hydroxyvitamin D [25(OH)D] and disease activity, inflammatory
      cytokines and bone loss/erosions in patients with RA. METHODS: The study included
      130 patients with RA and 80 healthy controls. Serum 25(OH)D, IL-17 and IL-23
      levels were detected by ELISA. Radiographic bone erosion was assessed using the
      van der Heijde modified Sharp score and BMD was measured using DXA. RESULTS:
      There were no significant differences in age, gender and BMI between the RA and
      control groups. Serum level of 25(OH)D was markedly lower in the RA group than in
      the control group [43.12 nmol/l (s.d. 15.59) vs 57.93 (15.95), P < 0.01]. In RA
      patients, 25(OH)D levels were significantly and negatively associated with
      clinical parameters of disease activity including swollen joint count, tender
      joint count, joint pain degree, morning stiffness time and HAQ score and
      laboratory measures including platelets and ESR after adjustment for gender, age
      and BMI. They were also negatively associated with serum levels of IL-17 and IL
      23. While 25(OH)D levels were not associated with radiographic bone erosions of
      RA, they were significantly lower in those with osteopenia and osteoporosis than
      in those with normal BMD (P < 0.01). CONCLUSION: 25(OH)D levels were reduced in
      patients with RA and were negatively associated with disease activity, IL-17/IL
      23 and bone loss in RA. These suggest that vitamin D deficiency may play a role
      in the aetiology of RA.

PMID- 24907154
TI  - Endothelial function in patients with familial Mediterranean fever-related
      amyloidosis and association with cardiovascular events.
AB  - OBJECTIVES: Secondary amyloidosis is the most important complication of FMF and
      endothelial function is more severely impaired. Elevated asymmetric dimethyl
      arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this
      group. We aimed to compare endothelial function characteristics, including ADMA,
      in patients with FMF-related amyloidosis and primary glomerulopathies and to
      define risk factors for a CVD event. METHODS: We undertook a cross-sectional
      study with prospective follow-up including consecutive patients with FMF-related
      amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All
      patients had nephrotic-range proteinuria and normal glomerular filtration rate.
      Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3
      (PTX3) were determined. Patients were followed for cardiovascular events.
      RESULTS: Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP
      and PTX3 and lower FMD as compared with patients with other glomerulopathies.
      Cardiovascular events (n = 54) were registered during 3 years of follow-up.
      Increased ADMA levels and lower FMD were observed in patients with cardiovascular
      risk in both groups, but especially in individuals with amyloidosis. CONCLUSION:
      Patients with FMF-related amyloidosis have increased CVD event risk, probably
      related to the high ADMA levels, elevated inflammatory markers and decreased FMD
      measures observed in these patients.

PMID- 24907155
TI  - Age at natural menopause among patients with systemic lupus erythematosus.
AB  - OBJECTIVE: The aim of this study was to estimate the age at natural menopause in
      women with SLE. METHODS: One thousand and thirty-nine consecutive SLE patients
      <60 years of age were surveyed. Demographic and clinical data were queried by a
      single investigator. SLE characteristics and co-morbidities were retrieved from
      their medical records. Natural menopause was defined as amenorrhoea >=12 months
      in the absence of previous hysterectomy, CYC exposure and severe chronic kidney
      disease (SCKD). Pregnant women and those with menses during the 12 months prior
      to interview were considered premenopausal. Median age at menopause was estimated
      by both logit and survival analyses. In addition, mean age at menopause was
      calculated for patients aged >=40 years. Factors associated with age at natural
      menopause were assessed by Cox regression analysis. RESULTS: A total of 961 SLE
      women were analysed. At interview, most patients (81.6%) were premenopausal, 7.9%
      had natural menopause, 6.3% were postmenopausal previously exposed to CYC, 4.1%
      had undergone hysterectomy before menopause and 0.1% presented with SCKD and
      amenorrhoea. The mean age at interview was 35.2 years (s.d. 10.1), the mean age
      at SLE diagnosis was 26.9 years (s.d. 8.6) and the mean duration of disease was
      8.2 years (s.d. 7.1). The mean recalled age at menopause was 46.4 years (s.d.
      4.7). Median age at menopause estimated by logit and survival analyses were 50.7
      and 50.8 years, respectively. Only the age at SLE diagnosis was associated with
      age at natural menopause. CONCLUSION: Median age at natural menopause in women
      with lupus is 50 years. This is consistent with the age at menopause reported in
      the general population.

PMID- 24907156
TI  - Vascular involvement in Behcet's syndrome: a retrospective analysis of
      associations and the time course.
AB  - OBJECTIVE: Some features of Behcet's syndrome (BS) tend to go together. We aimed
      to explore the association and timing of various vascular events in both the
      venous and the arterial vascular tree. METHODS: We conducted a chart survey on
      the type and time of vascular involvement of BS. The cross-relationships of
      involvement were assessed by phi correlation coefficients. Multiple
      correspondence analysis was used to identify patterns of vascular involvement.
      The risk of vascular recurrence was also estimated. RESULTS: We identified 882
      patients with vascular involvement among 5970 BS patients (14.7%). Deep vein
      thrombosis (DVT), almost always in the legs, was the most frequent single
      vascular event (592/882; 67.1%). The cumulative risk of a recurrent vascular
      event was 38.4% at 5 years. Patients with extrapulmonary artery involvement
      (EPAI) were significantly older than those with venous and pulmonary artery
      involvement (PAI). There were significant correlations between dural sinus
      thrombosis (DST) and PAI, Budd-Chiari syndrome (BCS) and inferior vena cava
      syndrome (IVCS) and between IVCS and superior vena cava syndrome (SVCS). Multiple
      correspondence analysis further indicated clustering of PAI, DST, BCS, IVCS and
      SVCS. However, EPAI and DVT clustered separately from forms of vascular disease,
      the separate clustering of the DVT being attributed to its propensity to occur
      solo. CONCLUSION: The most common type of vascular involvement in BS is solo DVT,
      almost always occurring in the legs. Various forms of venous disease in BS
      segregate together and PAI is included in this group. EPAI segregates separately.

PMID- 24907157
TI  - The reliability of a novel magnetic resonance imaging-based tool for the
      evaluation of forefoot bursae in patients with rheumatoid arthritis: the FFB
      score.
AB  - OBJECTIVE: The aim of this study was to determine the reliability of an MRI-based
      score that evaluates forefoot bursae (FFBs) in patients with RA. METHODS: Items
      for inclusion, grading criteria and MRI sequences were determined iteratively.
      The score was evaluated in 30 patients with established RA. Reader agreement was
      evaluated using the percentage of exact/close agreement, Bland-Altman plots,
      kappa and intraclass correlation coefficient analyses. RESULTS: The FFB score
      assesses nine forefoot regions and contains four items: presence, shape,
      enhancement and magnetic resonance characteristics. The FFB score showed moderate
      to good intra- and interreader agreement (kappa range = 0.5-0.9 and 0.47-0.87,
      respectively). CONCLUSION: The FFB score is adequately reliable in the evaluation
      of bursa-like lesions of the forefoot in patients with RA.

PMID- 24907159
TI  - Leuconostoc mesenteroides SJRP55: A Bacteriocinogenic Strain Isolated from
      Brazilian Water Buffalo Mozzarella Cheese.
AB  - The production of bacteriocins by Leuconostoc mesenteroides represents an
      important opportunity for exploration of their potential use for industrial
      purpose. The antimicrobial compounds produced by L. mesenteroides subsp.
      mesenteroides SJRP55 strain were characterized and purified. Cell-free
      supernatant of Leuc. mesenteroides subsp. mesenteroides SJRP55 produced
      antibacterial compounds against Listeria spp. strains and not inhibiting against
      Lactobacillus spp. The antimicrobial substances were stable at high temperatures
      (100  degrees C for 2 h and 121  degrees C for 20 min) and low pH (pH 2-4)
      values, but sensitive to proteolytic enzymes and resistant to alpha-amylase,
      lipase and catalase enzymes. The optimal temperature for active peptides
      production was 25  degrees C. The antimicrobial compounds were purified by
      ammonium sulfate precipitation, affinity column and reverse-phase chromatography.
      Mass spectrometry and amino acids analyses showed that the bacteriocins were
      identical to mesentericin Y105 and B105. The producer strain's DNA analysis
      revealed presence of open reading frames possibly coding for virulence factors,
      such as enterococcal surface protein (esp), collagen adhesion (ace) and intrinsic
      vancomycin resistance (vanA); however, biogenic amines encoding genes were not
      observed. Leuc. mesenteroides subsp. mesenteroides SJRP55 is a promising
      biopreservative culture in fermented milk, and the purified bacteriocins can also
      be applied in food preservation.

PMID- 24907160
TI  - Study on changes of clinical indicators and key proteins from fluoride exposure.
AB  - Few studies have evaluated the biomarker changes of fluoride exposure. In order
      to explore early and sensitive indicators, animal experiment was designed. Ninety
      six healthy SD rats (48 males and 48 females) weighing approximately 60 g were
      randomly divided into six groups of 16 animals each by gender average. Control
      animals were supplied with distilled water only as group 1. Exposure groups'
      animals were treated with 2, 4, 8, 16, and 32 mg NaF/kg bw, respectively, as
      groups 2, 3, 4, 5, and 6. Our study found that contents of white blood cell
      (WBC), lymphocyte percentage (LYMPH%), lymphocyte (LYM), mean platelet volume
      (MPV), and platelet distribution width (PDW) increased significantly in high
      fluoride-exposure groups (p < 0.05), which revealed that immune system may be
      interfered by high fluoride. Meanwhile, levels of alanine aminotransaminase
      (ALT), aspartate aminotransaminase (AST), and ALT/AST in groups 5 and 6 decreased
      significantly compared to those in control group (p < 0.05), as well as the
      concentration of uric acid (UA) in groups 3, 4, 5, and 6 exhibited the same
      trends (p < 0.05). On the contrary, the level of blood B2 microglobulin (BB2MG)
      increased significantly (p < 0.05) in groups 4, 5, and 6. Changes of ALT, AST,
      UA, and BB2MG suggested the functions of the liver and kidney be altered by
      fluoride exposure. At the same time, the ATF4 content decreased gradually with
      the increase of fluoride concentration; furthermore, a highly significant (r = 
      0.586, p < 0.01) negative relationship between ATF4 content and fluoride exposure
      level was found. Results meant that clinical indicators cannot act as indicators
      of high fluoride exposure, and it also suggested that protein ATF4 might be the
      early and sensitive indicator in epidemiologic study of high fluoride exposure.

PMID- 24907161
TI  - Effectiveness of protecting a zirconia bonding surface against contaminations
      using a newly developed protective lacquer.
AB  - OBJECTIVES: The purpose of this study was to test the effectiveness of a newly
      developed lacquer and its ability to protect pre-conditioned bonding surfaces of
      zirconia ceramic against contamination with saliva or silicone remnants. METHODS:
      Disk-shaped zirconia ceramic specimens were conditioned and cleaned using air
      abrasion. Before contamination with saliva or silicone, a newly developed
      protective lacquer (1% ethyl cellulose in ethanol) was applied to the bonding
      surface. After contamination, all specimens of the test groups were cleaned in an
      ultrasonic bath filled with 99% ethanol for 3 min and then air-dried. A universal
      primer (Monobond Plus) was applied to the surfaces and then the specimens were
      bonded to composite resin filled acrylic tubes using a luting resin (Multilink
      Automix). Each group (n=16) was divided into 2 subgroups (n=8). One subgroup was
      stored for 3 days in 37 degrees C tap water and the other subgroup was stored for
      150 days in 37 degrees C tap water interrupted by 37,500 thermal cycles between 5
      degrees C and 55 degrees C. After the storage, the bond strength was measured
      using a material testing machine. RESULTS: The specimens of the test groups
      showed comparable bond strengths to the positive control group after short-term
      storage. After artificial aging, bond strengths of the test groups were
      statistically significantly lower compared to the positive control and were
      statistically significantly higher compared to the negative control groups.
      SIGNIFICANCE: Overall, the use of the newly developed protective lacquer appears
      to be a promising approach to protect pre-conditioned surfaces of zirconia
      ceramics against contamination.

PMID- 24907162
TI  - 4D phase contrast MRI in the preterm infant: visualisation of patent ductus
      arteriosus.

PMID- 24907163
TI  - Severe hypercalcaemia due to subcutaneous fat necrosis: presentation, management
      and complications.
AB  - OBJECTIVE: Subcutaneous fat necrosis (SCFN) is a rare form of panniculitis in
      infants that generally occurs following birth trauma, meconium aspiration, or
      therapeutic cooling. Severe hypercalcaemia occurs in a subset of patients, but
      data on its presentation, management and outcomes are limited. This report
      details the clinical course and complications of infants treated for severe
      hypercalcaemia (peak serum calcium >=3.0 mmol/L) due to SCFN. DESIGN: Chart
      review of all infants with SCFN seen at a single paediatric centre over a 13-year
      period. PATIENTS: Seven infants with SCFN developed severe hypercalcaemia, with
      median peak serum calcium 4.1 mmol/L (range 3.3-5.1). RESULTS: Severe
      hypercalcaemia occurred before 6 weeks of age, and was asymptomatic in 3/7
      patients (43%). Most patients were treated with intravenous hydration,
      furosemide, glucocorticoids and low-calcium formula, which restored
      normocalcaemia in a median of 9 days (range 2-42). Fever developed during
      treatment in 4/7 infants (57%): two patients had bacterial infections and two had
      no infectious source identified. Nephrocalcinosis was present in 5/6 patients
      (83%) who were evaluated by renal ultrasound. Nephrocalcinosis failed to resolve
      in all cases over a median follow-up of 20 months (range 8-48), but no renal
      dysfunction was observed. Eosinophilia, which has not been reported previously in
      SCFN, was present in 6/7 patients (86%). CONCLUSIONS: In this largest series to
      date of infants with severe hypercalcaemia due to SCFN, novel findings include
      the common occurrence of fever and a high incidence of persistent
      nephrocalcinosis without evidence of adverse renal outcomes.

PMID- 24907164
TI  - Habituation responses to external stimuli: is the habituation of preterm infants
      at a postconceptual age of 40 weeks equal to that of term infants?
AB  - OBJECTIVE: Compare the habituation responses to external stimuli between preterm
      infants at the postconceptual age of 40 weeks and term infants in the first days
      of life, and evaluate the habituation responses of the preterm infants until the
      age of 40 postconceptual weeks. METHODS: Prospective cohort study of preterm
      infants aged <32 weeks. The habituation responses to light, rattle, bell and
      tactile stimuli of preterm infants were assessed at 32, 34, 36 and 38-40
      postconceptual weeks. External stimuli were presented and responses were scored
      according to Lester and Tronik (2004). Habituation scores were compared between
      preterm and term infants, matched by sex, using t test. Repeated measures ANOVA
      was used to compare the responses between the different postconceptual
      gestational ages. Contrast models were used to verify the differences between the
      habituation responses according to the type of stimulus and the postconceptual
      ages. RESULTS: 51 preterm infants were studied (gestational age 29.4+/-2.4w;
      birth weight 1230+/-323 g). The scores for the habituation responses to the four
      stimuli progressively increased with advancing postconceptual age. At the age of
      40 postconceptual weeks, the preterm infants were habituated to external stimuli
      similarly to the 51 studied term infants. The preterm infants showed higher
      habituation response scores for the rattle and bell stimuli than for the light
      and tactile stimuli. CONCLUSIONS: Preterm infants improve their habituation
      responses to external stimuli as their postconceptual age increases, and, at 40
      weeks of corrected age, they have similar responses to those exhibited by full
      term infants in the first days of life.

PMID- 24907165
TI  - Update on the management of pineal cysts: Case series and a review of the
      literature.
AB  - OBJECTIVE: The natural history of pineal cysts still remains unclear. Incidental
      pineal cysts have become more common which raises the question of their
      management. Symptomatic pineal cysts may require a surgical solution but
      therapeutic indications have not yet been clearly established. METHOD: From 1986
      to 2012, 26 patients with pineal cysts were identified. Their medical records
      were retrospectively assessed focusing on the initial symptoms, imaging
      characteristics of the cyst, management strategy, operative technique and their
      complications, as well as the latest follow-up. A systematic review of the
      literature is also presented. RESULTS: Twenty-six patients with pineal cysts were
      identified. The mean age was 23.5 years ranging from 7 to 49 years. Symptoms
      included intracranial hypertension with obstructive hydrocephalus in 18 cases and
      oculomotor anomalies in 12 cases. Two adult cases presented with non-specific
      headaches and did not require surgery. Twenty patients were operated via a
      suboccipital transtentorial approach with total removal of the cyst in 70% of the
      cases, while the remaining 4 cases were treated with an intraventricular
      endoscopic marsupialization associating a third ventriculostomy. Four patients
      required a preoperative ventriculo-peritoneal shunt due to life-threatening
      obstructive hydrocephalus. Overall, peri-operative mortality was nil. In the two
      non-operated patients, the cyst remained stable and no recurrences were observed
      in all operated patients with a mean follow-up of 144 months. CONCLUSION: In the
      majority of incidental pineal cysts, a clinical and imaging follow-up is
      sufficient but occasionally not required especially in adults as very rare cases
      of increase in size have been reported.

PMID- 24907166
TI  - Olfactory hallucination in childhood primary headaches: case series.
AB  - BACKGROUND: Although olfactory hallucination (OH) has been reported in patients
      with primary headaches, olfactory aura has not been recognised by the
      International Classification of Headache Disorders (ICHD-2). In this study, we
      examined the frequency and characteristics of OH among children and adolescents
      with primary headaches. METHODS: 839 neurologically normal patients with primary
      headaches (537 migraine) were eligible for the assessment of olfactory
      hallucination. Headache diagnosis was based on the ICHD. Data were prospectively
      collected during clinic sessions and using headache diaries. RESULTS: Olfactory
      hallucination was reported exclusively during headache attacks by 21/839 (2.5%)
      patients, all of whom had migraine. The prevalence of olfactory hallucination was
      3.9% among migraineurs (6.5% among those with migraine aura). Olfactory
      hallucination shortly followed the onset of headaches and lasted from 15 to 50
      minutes. Of those with MA, 10 patients had visual aura; two had somatosensory
      aura; one had motor aura; and two had a combination of visual and somatosensory
      aura. Using the ICHD-2, both OH and migraine aura occurred in the same headache
      attacks. In 12/15 patients, OH occurred simultaneously with migraine aura,
      whereas in 3/12 patients, it preceded aura. CONCLUSION: Our findings show that
      olfactory hallucination occurs in migraine and it has similarities to migraine
      aura.

PMID- 24907167
TI  - Exploding head syndrome: six new cases and review of the literature.
AB  - BACKGROUND: Exploding head syndrome (EHS) is characterized by attacks of a sudden
      noise or explosive feeling experienced in the head occurring during the
      transition from wake to sleep or from sleep to wake. METHODS: We present six new
      cases extending the clinical experience with the syndrome. We also reviewed all
      available cases from the scientific literature and evaluated the typical features
      of EHS. RESULTS: The female to male ratio is 1.5 to 1. The median age at onset is
      54. In average, one attack per day to one attack per week occurs. Some patients
      suffer from several attacks per night. In about half of all patients, a chronic
      time course can be observed but episodic or sporadic occurrence is also common.
      The most frequent accompanying symptoms beside the noise are fear and flashes of
      light. Polysomnographic studies do not reveal any specific sleep pattern
      associated with EHS. Tricyclic antidepressants are helpful in some patients.
      However, most patients do not need treatment because of the benign nature of the
      syndrome. CONCLUSION: EHS is a well-defined disease entity with a benign nature.

PMID- 24907168
TI  - Prevalence of obesity and systemic hypertension among diabetes mellitus patients
      attending an out-patient diabetes clinic in a Ghanaian Teaching Hospital.
AB  - AIMS: Diabetes Mellitus is now a prevalent disease in both developed and
      developing countries. Overweight/obesity and hypertension are potential
      modifiable risk factors for diabetes mellitus and persist during the course of
      the disease. This study was aimed at reporting the prevalence of
      overweight/obesity and systemic hypertension and their association to blood
      glucose levels in persons with diabetes mellitus attending a diabetic clinic in
      Ghanaian Teaching Hospital. MATERIALS AND METHODS: This cross-sectional study was
      conducted among 100 previously diagnosed diabetes mellitus patients attending a
      diabetic clinic at the Tamale Teaching Hospital, Ghana. Anthropometric variables
      of age, weight and height were measured with appropriate instruments, computed
      into BMI and classified according to WHO classifications. Systolic and diastolic
      blood pressures were measured by an appropriate instrument and classified by WHO
      standards. Fasting plasma glucose levels of the study participants were recorded
      from their personal health folder. All data was analysed by GraphPad prism
      version 5. RESULTS: In general, 7.0% of the participants were underweight and
      32.0% were overweight or obese. The mean+/-SD weight, height and BMI of the
      participants were 67.53+/-13.32, 1.68+/-0.12 and 24.18+/-5.32. Twenty-one percent
      of the studied participants were hypertensive. Mean+/-SD fasting plasma glucose
      of 7.94+/-2.82 was observed among the diabetic patients. As the prevalence of
      hyperglycaemia was higher among patients aged <=40 years (88.9% vs. 75.8%),
      normoglycaemia (11.1% vs. 24.2%) was higher among those over 40 years. The
      differences were not significant. The prevalence of hyperglycaemia was
      significantly higher in participants with overweight/obese (0.0% vs. 41.6%,
      p<0.0001) than those with underweight (26.1% vs. 1.3%, p=0.0005) and normal
      weight (73.9% vs. 57.1%, p=0.2228). CONCLUSION: A high prevalence of
      overweight/obesity and systemic hypertension was found. Hyperglycaemia was more
      prevalent among overweight/obese participants.

PMID- 24907169
TI  - Clinical profile of patients using normal, high and very high insulin doses in
      type 2 diabetes.
AB  - AIMS: Insulin requirement varies between patients with diabetes due to insulin
      resistance. The clinical profile of patients based on their insulin requirement
      has not been studied earlier. We stratified the patients based on total daily
      insulin requirement (TDIR) and studied their clinical profile and carbohydrate
      consumption. MATERIALS & METHODS: Sixty patients with type 2 diabetes (aged 30-75
      years, using stable insulin dose for last 6 months, HbA1c between 6-7.5%,
      negative screening tests for Acromegaly and Cushing's disease) participated in
      this clinical observational study. All patients with major illness, surgery or
      diabetic ketoacidosis were excluded. The patients were divided into 3 groups:
      Group 1 (TDIR<1 U/kg, n=30), Group 2 (TDIR 1-2 U/kg, n=20) and Group 3
      (TDIR>2U/kg, n=10). Data are presented as mean+/-S.D and comparison between three
      groups was done using one way ANOVA test. RESULTS: The patients (27M: 33F) had
      mean age 54.3 +/- 12.3 years, diabetes duration 10.1+/-4.7 years and an A1c of
      7+/-0.38%. Patients in group 3 had lower body weight, BMI and highest
      carbohydrate consumption when compared with the other two groups (P<0.05).
      Hypoglycemic episodes and complications did not differ between the groups.
      CONCLUSION: Our data showed that the low body weight and high carbohydrate intake
      are associated with increased insulin requirement. The clinical implications of
      our study are to check the carbohydrate intake in patients with high insulin
      requirement.

PMID- 24907170
TI  - Clustering of cardiometabolic risk factors and risk of elevated HbA1c in non
      Hispanic White, non-Hispanic Black and Mexican-American adults with type 2
      diabetes.
AB  - AIM: To determine which cardiometabolic risk factors and clusters of
      cardiometabolic risk factors that are mostly associated with elevated HbA1c in
      non-Hispanic White (NHW), non-Hispanic Black (NHB) and Mexican-American (MA)
      adults who have type 2 diabetes. METHODS: Data (n=2910) from the United States
      National Health and Nutritional Examination Surveys were used in this study.
      Elevated HbA1c was defined as having HbA1c value was 7% or greater.
      Race/ethnicity-specific associations of individual and clustered (2-5 factors)
      cardiometabolic risk factors with elevated HbA1c were determined using prevalence
      odds ratio from multivariate logistic regression analyses. Statistical
      adjustments were made for sex, age, education, income and marital status.
      RESULTS: Joint occurrence of abdominal obesity, high blood pressure, and elevated
      triglycerides and joint occurrence of high blood pressure, elevated triglycerides
      and low HDL were more highly associated with elevated odds of HbA1c compared to
      other cardiometabolic risk factors joint occurrences. Joint occurrences of
      abdominal obesity, high blood pressure, and elevated triglycerides was associated
      with 2.3 (95% CI: 1.2-3.3), 9.1 (95% CI: 2.9-28.7) and 4.8 (95% CI: 2.0-11.5)
      increased odds of elevated HbA1c in NHW, NHB and MA, respectively. The
      corresponding values for the joint occurrence of high blood pressure, elevated
      triglycerides and low HDL was associated with 2.4 (95% CI: 1.2-3.7), 3.5 (95% CI:
      1.1-5.5) and 2.6 (95% CI: 1.5-4.7) increased odds of elevated HbA1c in NHW, NHB
      and MA, respectively. CONCLUSION: This finding calls for consideration of
      cardiovascular risk factor clustering in deciding medical therapies to optimize
      glycemic control in individuals with type 2 diabetes. Interventions designed to
      achieve glycemic control coupled with modification of cardiometabolic risk
      factors may be crucial in alleviating sequelae resulting from type 2 diabetes.

PMID- 24907171
TI  - Incidence and risk of diabetes mellitus associated with depressive symptoms in
      adults: evidence from longitudinal studies.
AB  - AIMS: We estimated the incidence and risk of diabetes associated with depressive
      symptoms using data from longitudinal studies. MATERIALS AND METHODS: Databases
      were systematically searched for relevant studies. Incidence of diabetes is
      presented as cumulative incident proportion (CIP). Pooled effect sizes were
      calculated using random-effects model. The data were reconstructed to compute
      relative risk (RR). RESULTS: The 16 studies selected for review generated 16
      datasets of which 8 studies reporting binary estimates (RR) and 8 studies
      reporting time-to-event estimates (hazard ratio (HR)). Both RR and HR were
      significant at 1.67 (95% CI: 1.30-2.15) and 1.45 (95% CI: 1.12-1.87) for incident
      diabetes associated with depressive symptoms. CONCLUSION: Our observations
      revealed greater cumulative incidence of diabetes in depressed than in non
      depressed groups. Depression should be included among risk factors that required
      regular screening for diabetes.

PMID- 24907172
TI  - Association between high sensitivity C-reactive protein and metabolic syndrome in
      subjects completing the National Health and Nutrition Examination Survey (NHANES)
      2009-10.
AB  - AIMS: Metabolic syndrome and elevated high-sensitivity (hs) C-reactive protein
      (CRP) have been associated with an increase in risk of coronary artery disease,
      stroke, and diabetes but the relationship between the two is unclear. The purpose
      of this study is to identify any association between metabolic syndrome and hs
      CRP concentrations. METHODS: Subjects 20 years or older completing the 2009-10
      National Health and Nutrition Examination Survey (NHANES) were included.
      Metabolic syndrome was defined as having at least 3 of the following:
      hypertension, insulin resistance, hypertriglyceridemia, low high-density
      lipoprotein cholesterol, or high waist circumference. Elevated hs-CRP was defined
      as >3 mg/L. Multivariate logistic regression modeling was used to assess the
      relationship between hs-CRP and metabolic syndrome while controlling for
      potential confounders. RESULTS: A total of 5728 subjects met the inclusion
      criteria, of which 69% were 20-55 years old, and 52% were female. Overall
      prevalence of metabolic syndrome was 34% and hs-CRP concentrations were elevated
      in 32% of subjects. Number of metabolic syndrome conditions was significantly
      associated with increasing odds of elevated hs-CRP concentrations. Subjects with
      one, two, three, four, or five metabolic syndrome conditions had 2.4, 3.3, 5.1,
      10.7 and 11.1 times greater odds of elevated hs-CRP as compared to subjects with
      no metabolic syndrome conditions (p<0.05 for all comparisons). CONCLUSIONS:
      Presence of metabolic syndrome was common in subjects from NHANES 2009-10 and a
      significant "dose-related" association was confirmed between number of metabolic
      syndrome conditions and increasing odds of elevated hs-CRP concentration.

PMID- 24907173
TI  - The association of age, gender, ethnicity, family history, obesity and
      hypertension with type 2 diabetes mellitus in Trinidad.
AB  - AIMS: To assess the impact of risk factors such as age, gender, ethnicity, family
      history, body mass index (BMI), waist circumference and hypertension, on the
      development of type 2 diabetes mellitus in the Trinidadian population. MATERIALS
      AND METHODS: A cross-sectional case control study comprised 146 non-diabetics and
      147 type 2 diabetics >=18 years of age, from North Central, South West and
      Eastern regions of Trinidad. RESULTS: Cross-tabulations revealed a significant
      difference between type 2-diabetes and age at p<0.01, and between type 2 diabetes
      and family history, ethnicity, waist circumference and hypertension at p<0.05.
      Logistic regression showed age to be the most influential risk factor. The
      systolic blood pressure specifically showed a significant difference at p<0.05,
      with the mean values for non-diabetics and type 2 diabetics being, 130.62 (+/
      2.124) and 141.35 (+/-2.312), respectively. No significant difference was
      observed between type 2 diabetes and gender and BMI. CONCLUSIONS: Age was the
      most significant risk factor of type 2 diabetes. Therefore it can be concluded
      that family history, ethnicity, waist circumference and hypertension are more
      significant risk factors of this disease than BMI and gender in the Trinidadian
      population.

PMID- 24907174
TI  - Diagnostic accuracy of direct ophthalmoscopy for detection of diabetic
      retinopathy using fundus photographs as a reference standard.
AB  - AIMS: To determine the diagnostic accuracy of direct ophthalmoscopy for the
      presence and severity of diabetic retinopathy (DR) using fundus photographs as a
      reference standard. METHODS: Patients with type 2 diabetes attending the
      outpatient department (OPD) of a tertiary care diabetes center, from October 2009
      to March 2010 were recruited in the study after obtaining signed informed
      consent. Patients with type 1 diabetes and gestational diabetes or having eye
      problems were excluded. After checking visual acuity, direct ophthalmoscopy of
      each eye was done by diabetologist, followed by photography of two fields of
      retina by fundus camera. DR was graded by a retinal specialist, according to
      International Diabetic Retinopathy Disease Severity Scale. According to severity,
      patients with DR were grouped into non-sight threatening diabetic retinopathy
      (NSTDR) and sight threatening diabetic retinopathy (STDR). Sensitivity and
      specificity of direct ophthalmoscopy for detection of any retinopathy, NSTDR and
      STDR was calculated. RESULTS: A total of 728 eyes were examined by direct
      ophthalmoscopy as well as fundus photography. Sensitivity (95% CI) of direct
      ophthalmoscopy for any retinopathy, NSTDR and STDR was found to be 55.67% (50.58
      60.78), 37.63% (32.67-42.59) and 68.25% (63.48-73.02) respectively. Whereas,
      specificity of direct ophthalmoscopy was found to be 76.78% (72.45-81.11), 71.27%
      (CI: 66.63-75.91) and 90.0% (86.93-93.07) for any retinopathy, NSTDR and STDR
      respectively. CONCLUSION: The sensitivity and specificity of direct
      ophthalmoscopy performed by the diabetologist for the presence and severity of DR
      was lower compared to the recommended level of sensitivity and specificity of a
      screening test of DR.

PMID- 24907175
TI  - Burden of metabolic syndrome among HIV-infected patients in Southern Ethiopia.
AB  - BACKGROUND: HIV infection and highly active antiretroviral therapy (HAART) can
      induce metabolic disturbances including lipodystrophy, dyslipidemia, and insulin
      resistance, which are reminiscences of metabolic syndrome (MS). However, little
      is known regarding the magnitude of MS in Ethiopian HIV population. This study,
      aimed to estimate the prevalence of MS among HIV positive patients with and
      without HAART. METHODS: A cross-sectional study was conducted at Hawassa
      University Referral Hospital, southern Ethiopia between February 2012 and April
      2013. Data on demographic and anthropometric characteristics were collected from
      a total of 374 HIV positive participants (188 on ART and 186 on Pre-ART) using
      WHO stepwise approach. Fasting blood glucose, total cholesterol, triglyceride,
      HDL-cholesterol and LDL-cholesterol was measured. The International Diabetes
      Federation (IDF) and the National Cholesterol Education Program: Adult Treatment
      Panel III (ATP) Criteria were used to define MS. RESULT: Of the 374 study
      participants 68% were females, and 50.3% were receiving ART. Using the IDF
      criteria, metabolic syndrome was diagnosed in 25% of patients receiving ART
      compared to 22.5% of the ART naive group (OR: 1.14 CI: 0.71-1.84). Using the ATP
      criteria, the prevalence of MS was 18.1% in the ART groups compared to 15.6% in
      ART naive group (OR: 1.20, CI: 0.69-2.06). Patients receiving ART had
      significantly elevated Cholesterol, triglyceride, glucose and LDL-c levels but
      lower CD4(+) cell counts than the Pre-ART groups. Being a female, having BMI of
      at least 25, older age (i.e. age>=45 years) and having total cholesterol of at
      least 200mg/dl were significantly associated with the presence of MS. Using the
      ATP criteria to define MS, taking d4T-3TC-EFV regimen was significantly
      associated with higher odds of MS. CONCLUSION: Almost a quarter of HIV patients
      on ART developed metabolic syndrome. Furthermore patients on ART had elevated
      lipid profile and glucose metabolism disturbance than the ART naive.

PMID- 24907176
TI  - A study of diabetes complications in an endogamous population: an emerging public
      health burden.
AB  - AIM: The aims of this study were to determine the prevalence of diabetic
      complications namely neuropathy, nephropathy, and retinopathy among Qatari's DM
      patients; and to find associations between these complications and socio
      demographic and clinical characteristics in a highly consanguineous population.
      DESIGN: It is an observational cohort study. SETTING: The survey was carried out
      at the Hamad General Hospital and Primary Health Care (PHC) centers in the State
      of Qatar. SUBJECTS: The study was conducted from May 2011 to January 2013 among
      Qatari nationals above 20 years of age. Of the 2346 registered with diagnosed
      diabetes attending Hamad General Hospital and PHC centers, 1633 (69.3%) agreed
      and gave their consent to take part in this study. METHODS: Questionnaire
      included socio-demographic variables, body mass index (BMI), consanguinity,
      lifestyle habits, family history of diabetes, blood pressure and development of
      diabetes complications such as retinopathy, nephropathy, and neuropathy were
      collected at regular intervals throughout the follow-up. Univariate and
      multivariate statistical analysis were performed. RESULTS: Out of 1633 diabetic
      patients, 842 (51.6%) were males. The prevalence of diabetic nephropathy 12.4%
      and retinopathy was 12.5% followed by neuropathy 9.5% among diabetic population.
      The proportion of diabetic neuropathy and nephropathy were significantly higher
      among diabetic patients with age 60 years and above as compared to younger age
      groups (p=0.010). Nephropathy was significantly higher among male diabetic
      (p=0.014) and smokers (p<0.001) while diabetic neuropathy was more common among
      diabetic hypertensive patients (p=0.028). Multivariate logistic regression showed
      that Age (p=0.025), being male (p=0.045), and having high blood pressure
      (p=0.006) were significant predictors of diabetic neuropathy. For diabetic
      retinopathy, family history of DM (p<0.001), consanguinity (p=0.010), having high
      blood pressure (p=0.042) and physical activity (p<0.001) were significant
      predictors of diabetic retinopathy. Meanwhile, for diabetic nephropathy, age
      (p<0.001), smoking (p=0.045), physical activity (p<0.001) hypertension (p<0.001)
      and gender (p=0.012) were the significant predictors. CONCLUSION: Diabetes exerts
      a significant burden in Qatar, and this is expected to increase. Many diabetic
      patients face significant challenges accessing diagnosis and treatment, which
      contributes to the high morbidity and mortality and prevalence of complications
      observed. The significant interactions between diabetes and associated
      complications highlight the need and opportunity for health planners to develop
      integrated responses to communicable and non-communicable diseases.

PMID- 24907177
TI  - Indices of abdominal obesity may be better than the BMI to discriminate Latin
      American natives/mestizos with a poor cardiovascular status.
AB  - AIMS: To assess whether the anthropometric index used by the American Heart
      Association (AHA) to evaluate cardiovascular health (CVH) status, i.e., the body
      mass index (BMI), could also be of value in ethnic groups phenotypically
      different than Whites. METHODS: CVH status was evaluated in 616 Ecuadorian
      natives/mestizos aged >=40 years with the seven metrics proposed by the AHA.
      Then, the BMI was replaced by the waist-to-hip (WtoHp) and the waist-to-height
      (WtoHt) ratios to estimate whether these changes modify the CVH status and the
      presence of >=5 ideal metrics per person. RESULTS: Replacing the BMI for either
      the WtoHt or the WtoHp ratios reduces the percentage of persons with >=5 ideal
      CVH metrics from 13%, to 8% (p<0.004) and to 6.8% (p<0.0003), respectively. The
      number of persons with a poor CVH status increased when the WtoHt ratio was used
      instead of the BMI (81.5% versus 69.8%, p<0.0001). CONCLUSIONS: These results may
      explain the paradox "better CVH status/similar stroke prevalence" previously
      found in Ecuadorian natives/mestizos, and suggest that the WtoHt ratio could be
      the best anthropometric index to be included in the set of metrics used to
      evaluate the CVH status in populations that are phenotypically different than
      Whites.

PMID- 24907178
TI  - Association between alcohol consumption patterns and metabolic syndrome.
AB  - AIMS: Examine associations between self-reported alcohol consumption patterns and
      metabolic syndrome. MATERIALS AND METHODS: Sample (N=7432) included adult (>=20
      years) participants in the 1999-2006 National Health and Nutrition Examination
      Survey. RESULTS: Above moderate alcohol consumption (AMAC) was negatively
      associated with waist circumference among those in the 20-29, 40-49, and 70-79
      age groups (beta=-6.21, beta=-8.34, and beta=-6.60, respectively) and moderate
      alcohol consumption (MAC) was negatively associated with waist circumference
      among those in the 30-39, 40-49, and 70-79 age groups (beta=-4.60, beta=-5.69,
      and beta=-2.88, respectively). AMAC was negatively associated with triglycerides
      among those in the 70-79 and 80+ age groups (beta=-23.62 and beta=-34.18,
      respectively) and positively associated with HDL-C levels in all groups (beta
      range 8.96-18.25). MAC was positively associated with HDL-C in the age groups
      spanning 20-69 years (beta range 3.05-5.34) and those over 80 (beta=5.26). AMAC
      and MAC were negatively associated with fasting glucose levels in the 20-29 and
      70-79 age groups (beta=-3.38 and -15.61, respectively). MAC was negatively
      associated with fasting glucose levels among those 70-79 and those over 80 years
      of age (beta=-7.06 and beta=-5.00, respectively). CONCLUSION: MAC and AMAC may
      favorably impact metabolic health.

PMID- 24907179
TI  - Atherogenic lipids and vascular complications in a selected diabetic population
      with normal urinary albumin/creatinine ratios.
AB  - OBJECTIVE: To test the hypothesis that at different urinary albumin/creatinine
      ratios within the normal ranges, diabetics have low but similar prevalence of
      metabolic and micro vascular disease. METHODS: The study sample consisted of
      normotensive diabetics not taking any medications known to effect blood pressure
      and lipids. The data were collected from the Diabetes Register. The diabetics
      were subgrouped according to the urinary albumin/creatinine ratios. MA is defined
      as present if the albumin/creatinine ratio (ACR) is more than 2 mg/mmol. RESULTS:
      MA was present in 16% of the 152 diabetics. Total cholesterol, systolic BP, and
      triglycerides were significantly high in diabetics with ACR>=1<2 compared with
      <1. The prevalence rates for retinopathy and neuropathy in the MA group were also
      significantly high. However, a large number of diabetics without MA had had
      established complications (37% retinopathy, 40% neuropathy, and 16% peripheral
      vascular disease). Because these results were based on single early morning urine
      samples, we looked at their MA in the past year. After exclusion of regressed and
      progressed groups, the complications rate remained the same. CONCLUSION: The high
      prevalence of metabolic and vascular complications seen even in absence of MA
      indicates an early intervention and those diabetics should not wait unitl CVD
      risk scores raise to receive preventive treatment.

PMID- 24907180
TI  - Goal setting: an integral component of effective diabetes care.
AB  - Goal setting is a widely used behavior change tool in diabetes education and
      training. Prior research found specific relatively difficult but attainable goals
      set within a specific timeframe improved performance in sports and at the
      workplace. However, the impact of goal setting in diabetes self-care has not
      received extensive attention. This review examined the mechanisms underlying
      behavioral change according to goal setting theory and evaluated the impact of
      goal setting in diabetes intervention studies. Eight studies were identified,
      which incorporated goal setting as the primary strategy to promote behavioral
      change in individual, group-based, and primary care settings among patients with
      type 2 diabetes. Improvements in diabetes-related self-efficacy, dietary intake,
      physical activity, and A1c were observed in some but not all studies. More
      systematic research is needed to determine the conditions and behaviors for which
      goal setting is most effective. Initial recommendations for using goal setting in
      diabetes patient encounters are offered. 

PMID- 24907181
TI  - Frequency domain beamforming of magnetoencephalographic beta band activity in
      epilepsy patients with focal cortical dysplasia.
AB  - INTRODUCTION: Spike-based magnetoencephalography (MEG) source localization is an
      established method in the presurgical evaluation of epilepsy patients. Focal
      cortical dysplasias (FCDs) are associated with focal epileptic discharges of
      variable morphologies in the beta frequency band in addition to single epileptic
      spikes. Therefore, we investigated the potential diagnostic value of MEG-based
      localization of spike-independent beta band (12-30Hz) activity generated by
      epileptogenic lesions. METHODS: Five patients with FCD IIB underwent MEG. In one
      patient, invasive EEG (iEEG) was recorded simultaneously with MEG. In two
      patients, iEEG succeeded MEG, and two patients had MEG only. MEG and iEEG were
      evaluated for epileptic spikes. Two minutes of iEEG data and MEG epochs with no
      spikes as well as MEG epochs with epileptic spikes were analyzed in the frequency
      domain. MEG oscillatory beta band activity was localized using Dynamic Imaging of
      Coherent Sources. RESULTS: Intralesional beta band activity was coherent between
      simultaneous MEG and iEEG recordings. Continuous 14Hz beta band power correlated
      with the rate of interictal epileptic discharges detected in iEEG. In cases where
      visual MEG evaluation revealed epileptic spikes, the sources of beta band
      activity localized within <2cm of the epileptogenic lesion as shown on magnetic
      resonance imaging. This result held even when visually marked epileptic spikes
      were deselected. When epileptic spikes were detectable in iEEG but not MEG, MEG
      beta band activity source localization failed. DISCUSSION: Source localization of
      beta band activity has the potential to contribute to the identification of
      epileptic foci in addition to source localization of visually marked epileptic
      spikes. Thus, this technique may assist in the localization of epileptic foci in
      patients with suspected FCD.

PMID- 24907182
TI  - Natural course and predictors of spontaneous seizure remission in idiopathic
      generalized epilepsy: 7-27 years of follow-up.
AB  - The spontaneous course of idiopathic generalized epilepsy (IGE) is still
      controversial. The aim of this study was both to investigate the long-term
      spontaneous course and to identify factors that are predictive for epilepsy
      remission in a small cohort of 15 IGE patients (9 women) who refused
      antiepileptic drug (AED) treatment and therefore never have been treated with
      AED. All of them were reevaluated with a review of their medical records and
      direct face-to-face interview; the mean duration of follow-up was 15.3 years.
      Five (33.3%) of them had absence epilepsy (absence seizures, ABS), 5 had IGE with
      generalized tonic-clonic seizures (GTCS), and another 5 had both seizure types
      (IGE with ABS/GTCS). Rate of epilepsy remission was 53.3% with a mean time of
      seizure freedom of 13.1 years; rate of remission was highest among absence
      epilepsy patients (80%), followed by IGE with GTCS (60%) and IGE with ABS/GTCS
      (20%). The frequency of spontaneous generalized interictal epileptiform
      discharges in electroencephalography is not associated with the long-term seizure
      outcome (p=0.201) and per se does not require AED treatment. Furthermore, the
      occurrence of photoparoxysmal responses (p=0.020) as well as the occurrence of
      more than 3 GTCS during the course (p=0.029) were identified as significant
      predictors for a poor long-term seizure outcome which makes AED treatment
      indispensable in these patients. This study underlines the heterogenity of the
      group of IGE. AED treatment has no impact on the spontaneous course of IGE with
      ABS and/or GTCS. Several predictors for the long-term seizure outcome in patients
      with IGE were identified in this study.

PMID- 24907183
TI  - Zonisamide for refractory juvenile absence epilepsy.
AB  - PURPOSE: To examine the clinical effect of zonisamide (ZNS) in patients with drug
      resistant juvenile absence epilepsy (JAE). METHODS: Between 2006 and 2010, 13 JAE
      patients were successively treated with add-on ZNS. Safety and efficacy were
      assessed according to the patient and caregiver reports at visits every 3 months.
      Response rate was defined as a 50% or greater reduction in seizure frequency.
      RESULTS: Mean age was 42 years. No patient had been seizure free for a period
      >=12 months before ZNS. The mean follow-up was 34 months. The mean dosage of ZNS
      was 388 mg. ZNS was effective for absence seizures (AS) in all patients (more
      than 50% AS reduction). Four patients reached seizure reduction on 550-600
      mg/day. Three (23%) had a reduction in AS frequency >75% and five (38.5%) between
      50% and 75%. Seizure freedom was achieved in five patients (38.5%) (three
      patients with AS only and two with AS plus generalized tonic-clonic seizures
      (GTCS)). Before ZNS, four patients had AS evolving to absence status. After ZNS,
      three of them were in the seizure-free group, the later never experienced this
      type of complication. Among seven patients with AS plus GTCS, two of them did not
      report any improvement in the frequency of GTCS (29%). CONCLUSION: This
      observational post-marketing study confirms the broad-spectrum activity of ZNS
      that includes GTCS, myoclonic seizures and now AS. This study provides evidence
      that add-on ZNS is efficient and well tolerated in adult patients with refractory
      JAE, even at high doses.

PMID- 24907184
TI  - A novel FTL mutation responsible for neuroferritinopathy with asymmetric clinical
      features and brain anomalies.

PMID- 24907185
TI  - Low-dose abdominal CT protocols with a tube voltage setting of 100 kVp or 80 kVp:
      Performance of radiation dose reduction and influence on visual contrast.
AB  - AIM: To evaluate the radiation dose, image quality, and influence on visual
      contrast of low tube voltage abdominal computed tomography (CT) and the effects
      of display setting optimization. MATERIALS AND METHODS: One hundred and fifty
      seven patients were randomly assigned to one of three protocols. Fifty-two
      patients underwent a 120 kVp protocol, and 53 and 52 patients underwent low-dose
      protocols with 100 and 80 kVp, respectively. The effective dose (ED), image
      noise, CT attenuation, and signal-to-noise ratio (SNR) of each organ of each
      protocol were compared using Dunnett's test. Qualitative analysis between the
      protocols was also performed. RESULTS: The ED of the 100 and 80 kVp protocols
      were 22% and 37% reduced, respectively. There were no significant differences in
      the SNR between the protocols (120 kVp: 13.8 +/- 3.5; 100 kVp: 13.9 +/- 3.3; 80
      kVp: 13.5 +/- 2.9; p > 0.05). However, there were significant differences in
      contrast familiarity between the 120 kVp images and all the other images, except
      100 kVp images, with optimized display settings (p < 0.05). CONCLUSION: In
      abdominal CT, an 80 kVp setting offers greater radiation dose reduction than a
      100 kVp setting without significant deterioration of the SNR; however, the visual
      contrast between the organs might be changed.

PMID- 24907186
TI  - Molecular characterization of Rickettsia massiliae and Anaplasma platys infecting
      Rhipicephalus sanguineus ticks and domestic dogs, Buenos Aires (Argentina).
AB  - Rickettsioses, ehrlichioses and anaplasmoses are emerging diseases that are
      mainly transmitted by arthropods and that affect humans and animals. The aim of
      the present study was to use molecular techniques to detect and characterize
      those pathogens in dogs and ticks from Buenos Aires city. We studied 207
      Rhipicephalus sanguineus ticks and 52 canine blood samples from poor
      neighborhoods of Buenos Aires city. The samples were molecularly screened for the
      genera Rickettsia, Ehrlichia, and Anaplasma by PCR and sequencing. DNA of
      Rickettsia massiliae (3.4%) and Anaplasma platys (13.5%) was detected in ticks
      and blood samples, respectively. For characterization, the positive samples were
      subjected to amplification of a fragment of the 190-kDa outer membrane protein
      gene (spotted fever group rickettsiae) and a fragment of the groESL gene
      (specific for A. platys). A phylogenetic tree was constructed using the neighbor
      joining method, revealing that the sequences were closely related to those of
      strains from other geographic regions. The results indicate that human and animal
      pathogens are abundant in dogs and their ticks in Buenos Aires city and portray
      the potentially high risk of human exposure to infection with these agents,
      especially in poor neighborhoods, where there is close contact with animals in an
      environment of poor health conditions. 

PMID- 24907187
TI  - Tick-borne viruses: a review from the perspective of therapeutic approaches.
AB  - Several important human diseases worldwide are caused by tick-borne viruses.
      These diseases have become important public health concerns in recent years. The
      tick-borne viruses that cause diseases in humans mainly belong to 3 families:
      Bunyaviridae, Flaviviridae, and Reoviridae. In this review, we focus on
      therapeutic approaches for several of the more important tick-borne viruses from
      these 3 families. These viruses are Crimean-Congo hemorrhagic fever virus (CCHF)
      and the newly discovered tick-borne phleboviruses, known as thrombocytopenia
      syndromevirus (SFTSV), Heartland virus and Bhanja virus from the family
      Bunyaviridae, tick-borne encephalitis virus (TBEV), Powassan virus (POWV),
      Louping-ill virus (LIV), Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest
      disease virus (KFDV), and Alkhurma hemorrhagic fever virus (AHFV) from the
      Flaviviridae family. To date, there is no effective antiviral drug available
      against most of these tick-borne viruses. Although there is common usage of
      antiviral drugs such as ribavirin for CCHF treatment in some countries, there are
      concerns that ribavirin may not be as effective as once thought against CCHF.
      Herein, we discuss also the availability of vaccines for the control of these
      viral infections. The lack of treatment and prevention approaches for these
      viruses is highlighted, and we hope that this review may increase public health
      awareness with regard to the threat posed by this group of viruses. 

PMID- 24907189
TI  - [Prehospital ultrasound: time for a widespread use!].

PMID- 24907188
TI  - [To maintain or to withdraw life support? Variations on the methods of ending
      life in a pediatric intensive care unit over a period of 6 years].
AB  - Since 2005, forgoing live-support (FLS) is allowed by the French law (known as
      the Leonetti law) for end-of-life patients only. This study aims at describing
      the variations over time in the use of the following methods to end life: FLS,
      brain death and cardiopulmonary resuscitation failure (CPR failure). It is a
      single retrospective study from 2007 to 2012. The Cochran-Armitage trend test is
      used in the statistical analysis. Over six years, 263 of the 5100 children who
      were hospitalized in our intensive care unit died, which represents a 5.2%
      mortality rate. FLS increased yearly from 31% of the deaths in 2007, to 71% in
      2012 (P=0.0008). The rate of CPR failure decreased over the same period
      (P=0.0015). The rate of brain death remained constant. Following to the Leonetti
      law, FLS increase, and palliative cares develop without any increase of
      mortality. 

PMID- 24907190
TI  - The relationship between subacromial bursa thickness on ultrasound and shoulder
      pain in open water endurance swimmers over time.
AB  - OBJECTIVES: To help clinicians understand the clinical relevance of subacromial
      bursa (SAB) thickness on ultrasound investigations in marathon swimmers. DESIGN:
      A prospective, observational cohort study. METHODS: Twenty two open-water
      marathon swimmers entered in a 19.7km open-water event received comprehensive,
      bilateral, shoulder ultrasounds on three occasions: 4 months prior to the race, 2
      weeks prior to the race and within 1 week after the race. The SAB thickness was
      measured in the longitudinal plane of supraspinatus, with other abnormailities
      also recorded. The swimmers completed questionnaires detailing presence and
      severity of shoulder pain, volume of swimming completed that week and their
      breathing pattern. RESULTS: SAB thickness increased with season progression: mean
      of 1.55 (+/- 0.68) 4 months prior to the race, 1.63 (+/- 0.68) 2 weeks prior to
      the race and 1.86 (+/- 0.69) 1 week after the race. SAB thickness is
      significantly (p=0.05) correlated (beta=0.11) with kilometres swum in the pool in
      the preceding week. SAB thickness was not significantly correlated with pain when
      measured prior to the race. However, at 1 week post race, SAB thickness of
      shoulders with pain were significantly greater than those without pain, p
      value=0.032. CONCLUSIONS: SAB thickness increases with increasing swimming
      training. Commonly, this increase is not correlated to pain, suggestive of a
      painless adaptive process. The significant correlation between pain and SAB
      thickness soon after an exacerbating event suggests that painful acute SAB
      thickening is a different entity to chronic, painless adaptive SAB thickening.
      These two entities can only be differentiated by clinical history and
      examination.

PMID- 24907191
TI  - Assessing effect of three herbal medicines in second and third degree burns in
      rats and comparison with silver sulfadiazine ointment.
AB  - INTRODUCTION: Assessing effect of three herbal medicines on healing of deep
      second and third degree burns in rats and their comparison with silver
      sulfadiazine group. METHODS AND MATERIALS: 40 rats were randomly assigned to one
      of the four groups, each group 10 rats. A deep second degree burn and a third
      degree burn were induced on the lower back and upper back of each rat under
      standard burning procedure, respectively. The burns were daily dressed with
      Robacin in group 1, silver sulfadiazine in group 2, aloe vera extract in group 3,
      and Rimojen in group 4. Responses to the treatment were assessed by digital
      photography during the treatment until day 32. Histological parameters (PMN,
      epithelialization, fibrosis, and angiogenesis) were assessed after the scar
      biopsy at the end of the research. RESULTS: On the basis of the taken photos, the
      wound had better healing in Robacin group. Also, speed of healing was better in
      aloe vera group than silver sulfadiazine and Rimojen groups. In terms of wound
      surface area maximal improvement was observed at the same time in the second and
      third degree burn wounds in Robacin group, in the second degree wound of aloe
      vera and Rimojen groups, and in the third degree wound of aloe vera and silver
      sulfadiazine groups. In pathological respects, epithelialization was more evident
      in both wounds of aloe vera group and third degree burn of Robacin group. In both
      wounds of Robacin group (second and third degree), the extend of angiogenesis and
      fibrosis was significantly less than other groups; but, inflammation was at a
      less level in third degree of silver, second degree of Rimogen and aloe vera, and
      third degree of aloe vera groups. CONCLUSION: In histological survey, minimal
      rate of angiogenesis and fibrosis was seen in Robacin group, which indicated less
      wound scar in this group. Healing speed of the burn wound was also higher in
      Robacin group.

PMID- 24907192
TI  - Pre-hospital burn mission as a unique experience: a qualitative study.
AB  - INTRODUCTION: A thorough understanding of experiences related to pre-hospital
      emergency care of burns is a prerequisite of skill promotion for medical
      personnel. The aim of the present study was to evaluate the experiences of pre
      hospital emergency personnel during burn accidents. METHODS: The present
      qualitative study was performed using a content analysis method. In total, 18
      Iranian emergency care personnel participated in the study. A purposeful sampling
      method was applied until reaching data saturation. Data were collected using semi
      structured interviews and field observations. Afterwards, the gathered data were
      analyzed through face content analysis. RESULTS: By analyzing 498 primary codes,
      four main categories; the nature of burn care, tension at the accident scene,
      gradual job 'burnout', and insufficient information, were extracted from the
      experiences of pre-hospital emergency personnel during burn care. These
      categories each included several sub-categories, which were classified according
      to their significant characteristics. CONCLUSION: This study showed that
      different factors affect the quality of pre-hospital clinical services for burns.
      Authorities and health system administrators should consider the physical and
      psychological health of their staff, and assign policies to improve the quality
      of pre-hospital medical care. According to the present results, it is recommended
      that the process of pre-hospital emergency care for burns be investigated
      further.

PMID- 24907193
TI  - Validation of the Hebrew version of the Burn Specific Health Scale-Brief
      questionnaire.
AB  - BACKGROUND: The Burns Specific Health Scale-Brief (BSHS-B) questionnaire is a
      suitable measurement tool for the assessment of general, physical, mental, and
      social health aspects of the burn survivor. AIM: To translate, culturally adapt
      and validate the BSHS-B to Hebrew (BSHS-H), and to investigate its psychometric
      properties. METHODS: Eighty-six Hebrew speaking burn survivors filled out the
      BSHS-B and SF-36 questionnaires. Ten of them (11.63%) completed a retest. The
      psychometric properties of the scale were evaluated. Internal consistency,
      criterion validity, and construct validity were assessed using interclass
      correlation coefficient, Cronbach's alpha statistic, Spearman rank test, and Mann
      Whitney U test respectively. RESULTS: BSHS-H Cronbach's alpha coefficient was
      0.97. Test-retest interclass coefficients were between 0.81 and 0.98. BSHS-H was
      able to discriminate between facial burns, hand burns and burns >10% body surface
      area (p<0.05). BSHS-H and SF-36 were positively correlated (r(2)=0.667, p<0.01).
      CONCLUSIONS: BSHS-H is a reliable and valid instrument for use in the Israeli
      burn survivor population. The translation and cross-cultural adaptation of this
      disease specific scale allows future comparative international studies.

PMID- 24907194
TI  - Reconstruction following partial and total sacrectomy defects: an analysis of
      outcomes and complications.
AB  - BACKGROUND: Reconstruction of sacrectomy defects following ablative surgery
      remains a challenge, with high complication rates in the reported literature. The
      size of the defect is the primary consideration for flap choice; however, the
      cause of intra-abdominal and flap complications remains unclear. The aim of the
      study was to evaluate our results for sacrectomy flap reconstruction in order to
      determine predictive or protecting factors for complications. METHODS: A 13-year
      retrospective review was performed of all patients who had reconstruction for
      partial and total sacrectomy defects at the Mayo Clinic in Rochester, MN, USA.
      Demographics, flap choice, and complications were analyzed. Multivariate analysis
      was used to determine factors causing flap and intra-abdominal complications.
      RESULTS: Fifty-four patients underwent reconstruction. Partial sacrectomy was
      performed in 38 (70.4%) patients, while total sacrectomy was performed in 16
      (29.6%) patients. The average wound defect volume was 2136 cm(3) (range 196
      13,980 cm(3)). Flaps used included gluteal (n = 15; 27.8%), rectus abdominis
      myocutaneous (RAM) (n = 37; 68.5%), and combined gluteal/RAM (n = 2; 3.7%).
      Obesity was significantly associated with intra-abdominal complications (p <
      0.05) while preoperative radiotherapy and chemotherapy were not. Flap and wound
      healing complications were not significantly associated with any factors.
      CONCLUSIONS: Gluteal advancement and vertical RAM or transverse RAM flaps are
      both reliable options for reconstruction of sacrectomy defects. The use of
      acellular dermal matrix (ADM) for reconstructing the posterior abdominal wall
      provides a barrier between the intra-abdominal contents and flap, preventing
      bowel adhesions/obstruction and fistulas as well as prevents sacroperineal
      hernia.

PMID- 24907195
TI  - Evaluation of pain in patients with venous ulcers after skin grafting.
AB  - AIM: Pain was assessed in patients with venous leg ulcers treated with either
      split-thickness skin grafts or conventional treatment to evaluate to what extent
      skin grafting reduces pain in this population. METHODS: A controlled prospective
      clinical trial was conducted from July 2008 to June 2011 in two hospitals in Sao
      Paulo, Brazil. Two hundred patients with venous leg ulcers were divided into two
      treatment groups of 100 patients each: control group (conservative treatment) and
      surgery group (skin grafting). Patients were assessed at baseline (day 0) and
      after 30, 90, and 180 days. RESULTS: The surgery group reported significantly
      lower pain intensity (VAS pain scores) at postoperative days 30, 90 and 180 days
      compared with controls (P = 0.0001). The McGill Pain Questionnaire was used to
      assess the sensory, affective, evaluative, and miscellaneous dimensions of pain
      in both groups; there were significant differences between groups at the time
      points 30, 90 and 180 days (P = 0.0001). CONCLUSION: The patients with venous leg
      ulcers treated with split-thickness skin grafts reported significantly lower pain
      intensity compared with those who received conservative treatment.

PMID- 24907196
TI  - Iron distribution and histopathological characterization of the liver and heart
      of beta-thalassemic mice with parenteral iron overload: Effects of deferoxamine
      and deferiprone.
AB  - The liver and heart are the major target organs for iron accumulation and iron
      toxicity in beta-thalassemia. To mimic the phenomenon of heavy iron overload
      resulting from repeated blood transfusions, a total of 180 mg of iron dextran was
      intraperitoneally injected into C57BL/6J mice (WT) and heterozygous beta-globin
      knockout mice ((mu)beta(th-3/+), BKO). The effects of deferiprone and
      deferoxamine in this model were investigated. The iron was distributed
      homogenously throughout the 4 liver lobes (left, caudate, right and median) and
      was present in hepatocytes, Kupffer cells and the sinusoidal space. Iron
      accumulation in phagocytic macrophages, recruitment of hepatic lymphocytes and
      nucleus membrane degeneration were observed as a result of iron overload in the
      WT and BKO mice. However, the expansion of hepatic extramedullary hematopoiesis
      was observed only in the BKO mice with iron overload. In the heart, the iron
      accumulated in the cardiac interstitium and myocytes, and moderate hypertrophy of
      the myocardial fibers and cardiac myocyte degeneration were observed. Although
      the total liver iron was not significantly altered by iron chelation therapy,
      image analysis demonstrated a difference in the efficacies of two iron chelators.
      The major site of chelation was the extracellular compartment, but treatment with
      deferiprone also resulted in intracellular iron chelation. Interestingly, iron
      chelators reversed the pathological changes resulting from iron overload in WT
      and BKO mice despite being used for only a short treatment period. We suggest
      that some of these effects may be secondary to the anti-inflammatory activity of
      the chelators.

PMID- 24907197
TI  - [Paroxysmal nocturnal hemoglobinuria and intestinal ischemia: a very wide
      choice].
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is a rare hematologic disorder that
      can exceptionally be complicated by splanchnic thrombosis and intestinal
      necrosis. The discovery of multiple and dispersed distal ischemia of the small
      bowel is a real problem because the therapeutic approach depends on the range and
      the number of the segments to resect and also on the risk of recurrence of new
      peri-operative ischemic lesions. We report the case of a patient suffering from
      PNH, operated with the diagnosis of mesenteric infarction. We discovered multiple
      distal ischemic lesions of the gut extending from the first duodenum to the
      penultimate loop without perforation. Resection was then ruled out and curative
      anticoagulation was initiated. Outcome was favorable with restitution ad integrum
      of the digestive lesions without progression to secondary stenosis. Discovery of
      distal ischemic lesions without perforation in patients with PNH does not
      necessarily require resection. Curative anticoagulation can avoid surgery that
      may be insufficient.

PMID- 24907198
TI  - From behavior to mechanisms: an integrative approach to the manipulation by a
      parasitic fungus (Ophiocordyceps unilateralis s.l.) of its host ants (Camponotus
      spp.).
AB  - Co-evolution of parasites and their hosts has led to certain parasites adaptively
      manipulating the behavior of their hosts. Although the number of examples from
      different taxa for this phenomenon is growing, the mechanisms underlying parasite
      induced manipulation of hosts' behavior are still poorly understood. The
      development of laboratory infections integrating various disciplines within the
      life sciences is an important step in that direction. Here, we advocate for such
      an integrative approach using the parasitic fungi of the genus Ophiocordyceps
      that induce an adaptive biting behavior in Camponotus ants as an example. We
      emphasize the use of behavioral assays under controlled laboratory conditions,
      the importance of temporal aspects of the behavior (possibly involving the
      circadian clock), and the need to approach colonizing parasites as organizations
      with a division of labor. 

PMID- 24907199
TI  - Separating the nature and nurture of the allocation of energy in response to
      global change.
AB  - Understanding and predicting biological stability and change in the face of rapid
      anthropogenic modifications of ecosystems and geosystems are grand challenges
      facing environmental and life scientists. Physiologically, organisms withstand
      environmental stress through changes in biochemical regulation that maintain
      homeostasis, which necessarily demands tradeoffs in the use of metabolic energy.
      Evolutionarily, in response to environmentally forced energetic tradeoffs,
      populations adapt based on standing genetic variation in the ability of
      individual organisms to reallocate metabolic energy. Combined study of physiology
      and genetics, separating "Nature and Nurture," is, thus, the key to understanding
      the potential for evolutionary adaptation to future global change. To understand
      biological responses to global change, we need experimentally tractable model
      species that have the well-developed physiological, genetic, and genomic
      resources necessary for partitioning variance in the allocation of metabolic
      energy into its causal components. Model species allow for discovery and for
      experimental manipulation of relevant phenotypic contrasts and enable a systems
      biology approach that integrates multiple levels of analyses to map genotypic-to
      phenotypic variation. Here, we illustrate how combined physiological and genetic
      studies that focus on energy metabolism in developmental stages of a model marine
      organism contribute to an understanding of the potential to adapt to
      environmental change. This integrative research program provides insights that
      can be readily incorporated into individual-based ecological models of population
      persistence under global change. 

PMID- 24907200
TI  - What makes a feline fatal in Toxoplasma gondii's fatal feline attraction?
      Infected rats choose wild cats.
AB  - Toxoplasma gondii is an indirectly transmitted protozoan parasite, of which
      members of the cat family (Felidae) are the only definitive hosts and small
      mammals such as rats serve as intermediate hosts. The innate aversion of rodents
      to cat odor provides an obstacle for the parasite against successful predation by
      the feline definitive host. Previous research has demonstrated that T. gondii
      appears to alter a rat's perception of the risk of being preyed upon by cats.
      Although uninfected rats display normal aversion to cat odor, infected rats show
      no avoidance and in some cases even show attraction to cat odor, which we
      originally termed the "Fatal Feline Attraction." In this study, we tested for the
      first time whether the "Fatal Feline Attraction" of T. gondii-infected rats
      differed according to the type of feline odor used, specifically whether it came
      from domestic cats (Felis silvestris catus) or wild cats-cheetahs (Acinonyx
      jubatus) or pumas (Felis concolor). In two-choice odor trials, where wild and
      domestic cat odors were competed against one another, consistent with previous
      findings we demonstrated that infected rats spent more time in feline odor zones
      compared with uninfected rats. However, we further demonstrated that all cat
      odors are not equal: infected rats had a stronger preference for wild cat odor
      over that of domestic cats, an effect that did not differ significantly according
      to the type of wild cat odor used (cheetah or puma). We discuss these results in
      terms of the potential mechanism of action and their implications for the current
      and evolutionary role of wild, in addition to domestic, cats in transmission of
      T. gondii. 

PMID- 24907201
TI  - SeaBase: a multispecies transcriptomic resource and platform for gene network
      inference.
AB  - Marine and aquatic animals are extraordinarily useful as models for identifying
      mechanisms of development and evolution, regeneration, resistance to cancer,
      longevity and symbiosis, among many other areas of research. This is due to the
      great diversity of these organisms and their wide-ranging capabilities. Genomics
      tools are essential for taking advantage of these "free lessons" of nature.
      However, genomics and transcriptomics are challenging in emerging model systems.
      Here, we present SeaBase, a tool for helping to meet these needs. Specifically,
      SeaBase provides a platform for sharing and searching transcriptome data. More
      importantly, SeaBase will support a growing number of tools for inferring gene
      network mechanisms. The first dataset available on SeaBase is a developmental
      transcriptomic profile of the sea anemone Nematostella vectensis (Anthozoa,
      Cnidaria). Additional datasets are currently being prepared and we are aiming to
      expand SeaBase to include user-supplied data for any number of marine and aquatic
      organisms, thereby supporting many potentially new models for gene network
      studies. SeaBase can be accessed online at: http://seabase.core.cli.mbl.edu. 

PMID- 24907202
TI  - Metastatic cells: moving onco-targets.

PMID- 24907203
TI  - Obstructive sleep apnoea and arthrogryposis.
AB  - Arthrogryposis is a rare condition characterised by multiple congenital joint
      contractures. We present a case of a 10-year-old child with arthrogryposis and
      snoring. Polysomnography revealed significant obstructive sleep apnoea and
      hypoventilation that improved but did not completely resolve with
      adenotonsillectomy. With continuous positive airway pressure (CPAP) therapy,
      there was full resolution of all sleep disordered breathing. Initially, the
      patient admitted to difficulty tolerating nasal CPAP at home. However, she
      steadily improved adherence to therapy and admitted that with nasal CPAP use for
      the whole night, she felt more energised during the daytime. 

PMID- 24907204
TI  - Progressive intracranial hypertension and cerebral hypoperfusion in a fatal case
      of cerebral aspergilloma.
AB  - We report a case of cerebral aspergilloma in a 25-year-old immunoincompetent man
      admitted to a general intensive care unit. Monitoring of intracranial pressure
      was instigated and revealed hour-long epochs of severe intracranial hypertension,
      despite a normal opening pressure, with decreases in cerebral perfusion pressure.
      We documented that this was associated with cerebral hypoperfusion by
      transcranial Doppler ultrasound. The present case illustrates that severe
      intracranial hypertension may evolve despite a normal opening pressure; it
      furthermore shows that continuous monitoring of intracranial pressure may be used
      to predict changes in cerebral haemodynamics in critically ill patients with
      neuroinfection.

PMID- 24907205
TI  - 'Primary extrarenal Wilms' tumour': rare presentation of a common paediatric
      tumour.
AB  - Wilms' tumour (nephroblastoma), the most common abdominal malignancy of
      childhood, occurs primarily as a malignant renal tumour. Extrarenal Wilms' tumour
      is rare with occasional reports from the Indian subcontinent. The various
      locations of extrarenal Wilms' tumour include retroperitoneum, uterus, skin and
      thorax. In this report we will discuss the imaging features highlighting the
      imaging differential diagnosis in a case of retroperitoneal (extrarenal) primary
      Wilms' tumour. 

PMID- 24907207
TI  - An unusual presentation of a traumatic posterior hip dislocation.

PMID- 24907206
TI  - Atrioventricular block related to liposomal amphotericin B.
AB  - Atrioventricular block can occur in normal children, young adults or athletes. It
      is also associated with underlying heart disease or occurs as a drug adverse
      effect. Amphotericin B is used in the treatment of invasive fungal infections.
      Cardiac toxicity is a rare adverse reaction. We report the case of a 9-month
      girl, admitted in the paediatric intensive care unit with cytomegalovirus
      pneumonitis. During hospitalisation the patient developed a systemic fungic
      infection and was medicated with liposomal amphotericin B. On the third day of
      treatment she began repeated episodes of bradycardia with spontaneous reversion.
      The investigation revealed a second-degree atrioventricular block. We excluded
      the misplacement of the central catheter, myocarditis or structural
      cardiomyopathy and suspended amphotericin. After 8 days, the bradycardia episodes
      ceased what was consistent with the drug's half-life. Amphotericin cardiotoxic
      mechanism is still unclear. It may be related with alteration of myocardial
      membrane depolarisation.

PMID- 24907208
TI  - Chronological hypoplasia: aesthetic management.
AB  - Enamel hypoplasia is defined as a break in the continuity of enamel with a
      reduction in the layers leading to depressions or grooves. Chronological
      hypoplasia is differentiated from other forms of hypoplasia due to its
      characteristic presentation (multiple, symmetrical, chronological pattern).
      Chronological hypoplasias are seen at the time tooth erupts into the oral cavity
      leading to several problems like aesthetic problems, tooth sensitivity, caries
      and early pulpal involvement. Prevention of interaction of aetiological factors
      is not possible because multiple factors are required for enamel synthesis. This
      paper highlights how to diagnose, intercept and treat chronological hypoplasias.
      It also mentions reasons for treating a case and different modalities available. 

PMID- 24907209
TI  - A differential to consider in a case of non-healing skin lesion.

PMID- 24907210
TI  - Squamous cell carcinoma of external auditory canal lacking epidermal growth
      factor receptor protein overexpression, in an elderly Omani with oculocutaneous
      albinism treated with palliative radiotherapy.
AB  - We report a case of squamous cell carcinoma of external auditory canal in an
      Omani man with oculocutaneous albinism. The disease mimicked inflammatory process
      revealing positive cultures for various microorganisms during the course of his
      illness. He was eventually biopsied to rule out atypical infective process or
      presence of malignancy. He was staged as T4N0M0 and treated with radical doses of
      palliative radiation therapy which was very well tolerated and resulted in a
      complete resolution of disease clinically and a major soft tissue response on
      radiological imaging. Another unique finding was the absence of epidermal growth
      factor receptor (EGFR) protein overexpression in the tumour specimen. More than
      90% of mucosal squamous cell carcinoma (SCC) involving the head and neck region
      overexpress the EGFR protein in normal skin patients. SCC is the predominant
      cutaneous malignancy in albinos, and the presence of EGFR protein overexpression
      in cutaneous SCC is believed to be 56-58% in normal skin patients. The scientific
      literature is scarce on reporting incidence of EGFR overexpression in either
      cutaneous or mucosal SCC in albinos, and it remains to be defined whether being
      albino is the cause for its absence. 

PMID- 24907211
TI  - A case of unilateral phthiriasis palpebrarum infestation involving the left eye.
AB  - Phthiriasis palpebrarum is a rare cause of eyelid infestation. We report a case
      of unilateral phthiriasis palpebrarum. A 28-year-old man presented with moderate
      itching associated with lacrimation and irritation in the left eye. The initial
      evaluation of the patient revealed multiple white dots on the left upper
      eyelashes. Slit-lamp examination revealed multiple nits attached to the base and
      shaft of the cilia. There was no hyperaemia or discharge present in the
      conjunctiva and the cornea was clear and shiny. The right eye was perfectly
      normal. The patient was treated with moxifloxacin eye ointment and was completely
      cured in 1 week. 

PMID- 24907212
TI  - Hot tonsillectomy for paediatric obstructive sleep apnoea.
AB  - Obstructive sleep apnoea is a common presentation in paediatric ear, nose and
      tongue (ENT) outpatients. The use of sleep studies is controversial however once
      a diagnosis has been made, frequently treatment is surgery. Should these patients
      be operated on as urgent cases? A 5-year-old boy was admitted under the
      paediatric team with difficultly breathing and desaturations to 77%. The patient
      had previously been seen by ENT as an outpatient with an 8-month history of
      obstructive sleep apnoea and was listed for an adenotonsillectomy with the
      standard waiting time. During this admission he had an emergency
      adenotonsillectomy. The patient improved immediately with no large desaturations
      in recovery and normal observations throughout his stay. It is never ideal to do
      a paediatric emergency operation and we have reviewed the evidence base to answer
      the question: Should these patients be treated urgently when seen in outpatients?

PMID- 24907213
TI  - Pelvic arteriovenous malformation treated by transarterial glue embolisation
      combining proximal balloon occlusion and devascularisation of multiple feeding
      arteries.
AB  - We present a case of a 70-year-old man with abdominal aortic aneurysm and
      coincident pelvic arteriovenous malformation (AVM). Before the operation for the
      aneurysm, we embolised the pelvic AVM that had multiple feeding arteries and an
      aneurysmal-dilated draining vein. After decreasing the number of the feeding
      arteries by coil embolisation, an n-butyl-2-cyanoacrylate/lipiodol mixture (1:1)
      was injected into the prominent feeding artery and nidus with proximal balloon
      occlusion of the right internal iliac artery to decrease the flow to the nidus.
      The mixture (1:4-8) was also added for the finer feeding arteries that became
      apparent after the initial procedure to embolise the rest of the nidus. A follow
      up study showed no contrast enhancement of the nidus and aneurysmal draining
      vein. 

PMID- 24907214
TI  - Acute hepatitis C infection in a renal transplant recipient: primacy of the liver
      or kidney?
AB  - We present a case where a renal transplant recipient contracted chronic hepatitis
      C virus (HCV) infection post-transplantation. The disease progressed and
      deteriorated leading to fibrosing cholestatic hepatitis that mandated treatment.
      Treatment with pegylated interferon alpha-2a and ribavirin was successful in
      salvaging the liver and eradicating the virus but as a consequence lead to
      treatment-resistant acute rejection and loss of the renal allograft. 

PMID- 24907215
TI  - Implant rehabilitation in bruxism patient.
AB  - A white female patient presented to the university clinic to obtain implant
      retained prostheses. She had an edentulous maxillary jaw and presented three
      teeth with poor prognosis (33, 34 and 43). The alveolar bone and the surrounding
      tissues were healthy. The patient did not report any relevant medical history
      contraindicating routine dental treatment or implant surgery, but self-reported a
      dental history of asymptomatic nocturnal bruxism. The treatment plan was set and
      two Branemark protocols supported by six implants in each arch were installed
      after a 6-month healing period. A soft occlusal splint was made due to the
      patient's history of bruxism, and the lack of its use by the patient resulted in
      an acrylic fracture. The prosthesis was repaired and the importance of using the
      occlusal splint was restated. In the 4-year follow-up no fractures were reported.

PMID- 24907216
TI  - Hepatic PEComa: a potential pitfall in the evaluation of hepatic neoplasms.
AB  - Perivascular epithelioid cell tumour (PEComa) of the liver is very uncommon and
      may be overlooked in the clinical and histological differential diagnosis of a
      liver tumour. We report the case of an incidentally discovered liver mass
      suspicious for hepatocellular carcinoma, which on biopsy was suggestive of a
      pseudocyst but after resection was found to be hepatic PEComa with some of the
      usual characteristics of this neoplasm as well as several less familiar features.
      We have also reviewed cases of hepatic PEComa from the literature in order to
      provide insight into recognising possible PEComa preoperatively and assessing its
      risk of malignancy after diagnosis. 

PMID- 24907217
TI  - Metastasising pleomorphic salivary gland adenoma presenting as synchronous
      pulmonary and hepatic metastases.
AB  - Pleomorphic salivary adenomas (PAs) are the commonest benign tumours of glandular
      origin in the head and neck. Occasionally PAs undergo malignant transformation to
      carcinoma-ex-PA and can metastasise. More rarely they metastasise without
      malignant transformation of the primary tumour. We present a case of a benign
      pleomorphic salivary gland adenoma, presenting 7 years later with multiple liver
      metastases and a synchronous pulmonary metastasis. Histological analysis of the
      lung and liver lesions confirmed a diagnosis of metastasising pleomorphic adenoma
      (MPA). The lung lesion was fully excised, but the multifocal nature of the liver
      lesions rendered them inoperable. The patient is being managed conservatively and
      to date has no local recurrence of the primary salivary gland tumour or any
      further metastases. To the best of our knowledge this is the first case of MPA
      with simultaneous metastasis to both lungs and liver, and also the first to
      describe multiple liver metastases.

PMID- 24907218
TI  - An unusual unilateral benign congenital anomaly of the pupil.

PMID- 24907220
TI  - Cerebellar atrophy in neuroacanthocytosis.

PMID- 24907219
TI  - Management of a mixed overdose of calcium channel blockers, beta-blockers and
      statins.
AB  - We describe a case of extreme mixed overdose of calcium channel blockers, beta
      blockers and statins. The patient was successfully treated with aggressive
      resuscitation including cardiac pacing and multiorgan support, glucagon and high
      dose insulin for toxicity related to calcium channel blockade and beta-blockade,
      and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and
      muscle weakness. 

PMID- 24907221
TI  - Atypical neuroimaging in Wilson's disease.
AB  - Wilson's disease is a rare metabolic disease involving copper metabolism.
      Neuroimaging plays an important part in evaluation of patients with a
      neuropsychiatric presentation. We present a case of a 14-year-old girl with
      atypical confluent white matter disease and cystic degeneration on MRI, with a
      rapidly progressive course, who succumbed to complications despite treatment with
      trientine. Wilson's disease should be considered as a differential for
      leucoencephalopathy in young patients with progressive neurological disease for
      its early recognition and optimum outcome. 

PMID- 24907223
TI  - QUEST for a cure for hepatitis C virus: the end is in sight.

PMID- 24907222
TI  - Prenatal maternal stress predicts autism traits in 61/2 year-old children:
      Project Ice Storm.
AB  - Research implicates prenatal maternal stress (PNMS) as a risk factor for
      neurodevelopmental disorders; however few studies report PNMS effects on autism
      risk in offspring. We examined, prospectively, the degree to which objective and
      subjective elements of PNMS explained variance in autism-like traits among
      offspring, and tested moderating effects of sex and PNMS timing in utero.
      Subjects were 89 (46F/43M) children who were in utero during the 1998 Quebec Ice
      Storm. Soon after the storm, mothers completed questionnaires on objective
      exposure and subjective distress, and completed the Autism Spectrum Screening
      Questionnaire (ASSQ) for their children at age 61/2. ASSQ scores were higher
      among boys than girls. Greater objective and subjective PNMS predicted higher
      ASSQ independent of potential confounds. An objective-by-subjective interaction
      suggested that when subjective PNMS was high, objective PNMS had little effect;
      whereas when subjective PNMS was low, objective PNMS strongly affected ASSQ
      scores. A timing-by-objective stress interaction suggested objective stress
      significantly affected ASSQ in first-trimester exposed children, though less so
      with later exposure. The final regression explained 43% of variance in ASSQ
      scores; the main effect of sex and the sex-by-PNMS interactions were not
      significant. Findings may help elucidate neurodevelopmental origins of non
      clinical autism-like traits from a dimensional perspective. 

PMID- 24907224
TI  - Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment
      naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a
      randomised, double-blind, placebo-controlled phase 3 trial.
AB  - BACKGROUND: Pegylated interferon (peginterferon) alfa 2a or 2b plus ribavirin
      regimens were the standard of care in patients with hepatitis C virus (HCV)
      infection, but the sustained virological response can be suboptimum in patients
      with HCV genotype 1 infection. The efficacy, safety, and tolerability of the
      combination of simeprevir, a one-pill, once-daily, oral HCV NS3/4A protease
      inhibitor versus placebo, plus peginterferon alfa 2a or 2b plus ribavirin was
      assessed in treatment-naive patients with HCV genotype 1 infection. METHODS: In
      the QUEST-2, phase 3 study, done at 76 sites in 14 countries (Europe, and North
      and South Americas), patients with confirmed chronic HCV genotype 1 infection and
      no history of HCV treatment were randomly assigned with a computer-generated
      allocation sequence in a ratio of 2:1 and stratified by HCV genotype 1 subtype
      and host IL28B genotype to receive simeprevir (150 mg once daily, orally),
      peginterferon alfa 2a (180 MUg once weekly, subcutaneous injection) or 2b
      (according to bodyweight; 50 MUg, 80 MUg, 100 MUg, 120 MUg, or 150 MUg once
      weekly, subcutaneous injection), plus ribavirin (1000-1200 mg/day or 800-1400
      mg/day, orally; simeprevir group) or placebo (once daily, orally), peginterferon
      alfa 2a or 2b, plus ribavirin (placebo group) for 12 weeks, followed by just
      peginterferon alfa 2a or 2b plus ribavirin. Total treatment duration was 24 weeks
      or 48 weeks (simeprevir group) based on criteria for response-guided therapy (ie,
      HCV RNA <25 IU/mL undetectable or detectable at week 4 and undetectable week 12)
      or 48 weeks (placebo). Patients, study personnel, and the sponsor were masked to
      treatment assignment. The primary efficacy endpoint was sustained virological
      response at 12 weeks after the planned end of treatment (SVR12). Analyses were by
      intention to treat. The trial is registered with ClinicalTrials.gov, number
      NCT01290679. Results from the primary (SVR12, week 60) analysis are presented.
      FINDINGS: 209 (81%) of 257 patients in the simeprevir group and 67 (50%) of 134
      in the placebo group had SVR12 (adjusted difference 32.2%, 95% CI 23.3-41.2;
      p<0.0001). The incidences of adverse events were similar in the simeprevir and
      placebo groups at 12 weeks (246 [96%] vs 130 [97%]) and for the entire treatment
      (249 [97%] vs 132 [99%]), irrespective of the peginterferon alfa used. The most
      common adverse events were headache, fatigue, pyrexia, and influenza-like illness
      at 12 weeks (95 [37%) vs 45 [34%], 89 [35%] vs 52 [39%], 78 [30%] vs 48 [36%],
      and 66 [26%] vs 34 [25%], respectively) and for the entire treatment (100 [39%]
      vs 49 [37%], 94 [37%] vs 56 [42%], 79 [31%] vs 53 [40%], and 66 [26%] vs 35
      [26%], respectively). Rash and photosensitivity frequencies were higher in the
      simeprevir group than in the placebo group (61 [24%] vs 15 [11%] and ten [4%] vs
      one [<1%], respectively). There was no difference in the prevalence of anaemia
      between the simeprevir and placebo groups (35 [14%] vs 21 [16%], respectively, at
      12 weeks, and 53 [21%] vs 37 [28%], respectively, during the entire treatment).
      INTERPRETATION: Addition of simeprevir to either peginterferon alfa 2a or
      peginterferon alfa 2b plus ribavirin improved SVR in treatment-naive patients
      with HCV genotype 1 infection, without worsening the known adverse events
      associated with peginterferon alfa plus ribavirin. FUNDING: Janssen Infectious
      Diseases-Diagnostics.

PMID- 24907225
TI  - Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive
      patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase
      3, randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Although the addition of the HCV NS3/4A protease inhibitors
      boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus
      ribavirin has improved sustained virological response (SVR) in treatment-naive
      and treatment-experienced patients infected with hepatitis C virus (HCV) genotype
      1, the regimens have a high pill burden and are associated with increased rates
      and severity of adverse events, such as anaemia and rash. The efficacy and safety
      of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A
      protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in
      treatment-naive patients with HCV genotype 1 infection. METHODS: In QUEST-1, a
      phase 3, randomised, double-blind multicentre trial undertaken in 13 countries
      (Australia, Europe, North America, Puerto Rico, and New Zealand), 394 patients
      (aged >=18 years) with chronic HCV genotype 1 infection and no history of HCV
      treatment, stratified by HCV subtype and host IL28B genotype, were randomly
      assigned in a 2:1 ratio with a computer-generated allocation sequence to receive
      simeprevir (150 mg once daily, orally) plus peginterferon alfa 2a plus ribavirin
      for 12 weeks, followed by peginterferon alfa 2a plus ribavirin (simeprevir
      group), or placebo orally plus peginterferon alfa 2a plus ribavirin for 12 weeks,
      followed by peginterferon alfa 2a plus ribavirin (placebo group). Treatment
      duration was 24 weeks or 48 weeks in the simeprevir group according to criteria
      for response-guided therapy (ie, HCV RNA <25 IU/mL [undetectable or detectable]
      at week 4 and <25 IU/mL undetectable at week 12) and 48 weeks in the placebo
      group. Patients, study personnel, and the sponsor were masked to the treatment
      group assignment. The primary efficacy endpoint was sustained virological
      response 12 weeks after the planned end of treatment (SVR12) and was assessed
      with an intention-to-treat analysis. The results of the primary analysis (week
      60) are presented for safety and SVR12. This trial is registered with
      ClinicalTrials.gov, number NCT01289782. FINDINGS: Treatment with simeprevir,
      peginterferon alfa 2a, and ribavirin was superior to placebo, peginterferon alfa
      2a, and ribavirin (SVR12 in 210 [80%] patients of 264 vs 65 [50%] of 130,
      respectively, adjusted difference 29.3% [95% CI 20.1-38.6; p<0.0001). Adverse
      events in the first 12 weeks of treatment led to discontinuation of simeprevir in
      two (<1%) patients and discontinuation of placebo in one patient (<1%); fatigue
      (106 [40%] vs 49 [38%] patients, respectively) and headache (81 [31%] vs 48
      [37%], respectively) were the most common adverse events. The prevalences of
      anaemia (42 [16%] vs 14 [11%], respectively) and rash (72 [27%] vs 33 [25%]) were
      similar in the simeprevir and placebo groups. Addition of simeprevir did not
      increase severity of patient-reported fatigue and functioning limitations, but
      shortened their duration. INTERPRETATION: Simeprevir once daily with
      peginterferon alfa 2a and ribavirin shortens therapy in treatment-naive patients
      with HCV genotype 1 infection without worsening the adverse event profiles
      associated with peginterferon alfa 2a plus ribavirin. FUNDING: Janssen Infectious
      Diseases-Diagnostics.

PMID- 24907226
TI  - Systematic review of endovascular therapy for nutcracker syndrome and case
      presentation.
AB  - BACKGROUND: The left renal vein (LRV) entrapment syndrome is a rare condition.
      Here, we present a 22-year-old female presenting with recurrent nausea, vomiting,
      weight loss and evidence of the LRV compression by the superior mesenteric artery
      and the abdominal aorta. Hemodynamic assessment confirmed a pressure gradient of
      >3 mmHg between the LRV and the inferior vena cava. A self-expandable stent was
      then deployed in the LRV. Subsequent clinical follow-ups ensure full resolution
      of the patient's symptoms. METHODS: Multilingual search was performed in PubMed,
      Google scholar, Scielo, Korea Med and EMBASE with the medical subheadings
      "nutcracker syndrome", "nutcracker phenomenon" and "compression vein syndrome"
      from January 1983 to September 2013. RESULTS: Review of the literature exhibited
      a plethora of individual case reports (291 citations). Importantly, few
      retrospective case series [5] comprising a total of 157 patients included
      successful endovascular interventions. CONCLUSION: Endovascular therapy for
      nutcracker syndrome represents a safe and suitable treatment option, but
      prospective studies are needed to confirm these data.

PMID- 24907227
TI  - Intrapulmonary schwannoma diagnosed with endobronchial ultrasound-guided
      transbronchial needle aspiration: case report.
AB  - A 47-year-old woman was referred to our hospital for further examination of a
      lung tumor. CT of the chest revealed a round, well-defined 2.4-cm nodule in S2,
      adjacent to right superior lobe bronchus. Endobronchial ultrasonography showed a
      well-defined, hypoechoic tumor with echogenic capsule and posterior acoustic
      enhancement. Diagnosis of schwannoma was confirmed from the specimen obtained by
      endobronchial ultrasound-guided transbronchial needle aspiration. She underwent
      tumorectomy due to the possibility of obstructive pneumonia. Pathology diagnosis
      from the surgical specimen was also schwannoma. Endobronchial ultrasound-guided
      transbronchial needle aspiration and findings with endobronchial ultrasonography
      might be helpful in the diagnosis of intrapulmonary schwannoma. 

PMID- 24907228
TI  - Partners in projects: preparing for public involvement in health and social care
      research.
AB  - In recent years, several UK and, international funders of health and social care
      related research have adopted the policy of requiring explicit evidence of the
      'public' voice in all aspects of project design. For many academic researchers
      engaged within research, evaluations or audit projects, this formal requirement
      to actively engage members of the public will present them with both benefits and
      challenges to securing knowledgeable, skilled, and confident lay representation
      onto project teams. This could potentially lead to the exploitation of those
      individuals who are available, appropriately informed, and adequately prepared
      for such activities. Currently, much of the preparation of patients or members of
      the public for research involvement tends to be aligned to specific projects;
      however, with the call for greater active and meaningful involvement of lay
      representatives in future national and international funding applications, there
      is clearly a growing need to 'train' sufficient numbers of confident and
      competent representatives to meet this growing demand. This paper describes the
      development of a specifically designed research awareness training programme and
      underpinning theoretical model, which has been specifically designed to support
      active and meaningful lay involvement in research, evaluations and audit
      projects. Developed over a four year period, the course is a culmination of
      learning extracted from a series of four completed research projects, which have
      incorporated an element of public and patient involvement (PPI) training in their
      overall design. 

PMID- 24907229
TI  - A new model for mitochondrial membrane potential production and storage.
AB  - Mitochondrial membrane potential (MMP) is the most reliable indicator of
      mitochondrial function. The MMP value range of -136 to -140mV has been considered
      optimal for maximum ATP production for all living organisms. Even small changes
      from the above range result in a large fall in ATP production and a large
      increase in ROS production. The resulting bioenergetic deregulation is considered
      as the causative agent for numerous major human diseases. Normalization of MMP
      value improves mitochondrial function and gives excellent therapeutic results. In
      order for a systematic effective treatment of these diseases to be developed, a
      detailed knowledge of the mechanism of MMP production is absolutely necessary.
      However, despite the long-standing research efforts, a concrete mechanism for MMP
      production has not been found yet. The present paper proposes a novel mechanism
      of MMP production based on new considerations underlying the function of the two
      basic players of MMP production, the electron transport chain (ETC) and the F1F0
      ATP synthase. Under normal conditions, MMP is almost exclusively produced by the
      electron flow through ETC complexes I-IV, creating a direct electric current that
      stops in subunit II of complex IV and gradually charges MMP. However, upon ETC
      dysfunction F1F0 ATP synthase reverses its action and starts to hydrolyze ATP.
      ATP hydrolysis further produces electric energy which is transferred, in the form
      of a direct electric current, from F1 to F0 where is used to charge MMP. This new
      model is expected to redirect current experimental research on mitochondrial
      bioenergetics and indicate new therapeutic schemes for mitochondrial disorders. 

PMID- 24907230
TI  - Truth-telling to patients' terminal illness: what makes oncology nurses act
      individually?
AB  - PURPOSE: Nurses encounter the challenge of truth-telling to patients' terminal
      illness (TTPTI) in their daily care activities, particularly for nurses working
      in the pervasive culture of family protectiveness and medical paternalism. This
      study aims to investigate oncology nurses' major responses to handling this issue
      and to explore what factors might explain oncology nurses' various actions.
      METHODS: A pilot quantitative study was designed to describe full-time nurses' (n
      = 70) truth-telling experiences at an oncology centre in Taipei. The potential
      influencing factors of nurses' demographic data, clinical characteristics, and
      truth-telling attitudes were also explored. RESULTS: Most nurses expressed that
      truth-telling was a physician's responsibility. Nevertheless, 70.6% of nurses
      responded that they had performed truth-telling, and 20 nurses (29.4%) reported
      no experience. The reasons for inaction were "Truth-telling is not my duty",
      "Families required me to conceal the truth", and "Truth-telling is difficult for
      me". Based on a stepwise regression analysis, nurses' truth-telling acts can be
      predicted based on less perceived difficulty of talking about "Do not
      resuscitate" with patients, a higher perceived authorisation from the unit, and
      more oncology work experience (adjusted R2 = 24.1%). CONCLUSIONS: Oncology care
      experience, perceived comfort in communication with terminal patients, and unit
      authorisation are important factors for cultivating nurses' professional
      accountability in truth-telling. Nursing leaders and educators should consider
      reducing nursing barriers for truth-telling, improving oncology nurses'
      professional accountability, and facilitating better quality care environments
      for terminal patients.

PMID- 24907231
TI  - Serum FGF21 levels in adult m.3243A>G carriers: clinical implications.
AB  - OBJECTIVES: To determine the value of fibroblast growth factor 21 (FGF21), a
      recently discovered biomarker for mitochondrial disease, in predicting clinical
      disease severity and disease progression in adult carriers of the m.3243A>G
      mutation. METHODS: In the context of a national inventory, the heteroplasmy
      levels of the m.3243A>G mutation were measured in leukocytes and urinary
      epithelial cells. The Newcastle Mitochondrial Disease Adult Scale score was
      determined and blood was drawn for measuring FGF21 concentration. Twenty-five of
      the included initial patients studied were then selected randomly for a follow-up
      study. RESULTS: This prognostic study included 99 adult carriers of the m.3243A>G
      mutation. Our analysis revealed a moderate, significant correlation between FGF21
      concentration and disease severity (r = 0.49; p = <0.001). No significant
      correlations were found between disease severity and the heteroplasmy percentage
      determined in urinary epithelial cells or the heteroplasmy percentage determined
      in leukocytes. Weak but significant correlations were also found between FGF21
      concentration and the severity of the myopathy (r = 0.38; p = <0.001) and between
      the concentration of FGF21 and the severity of the encephalopathy (r = 0.30; p =
      <0.001). Repeated measurements following 25 subjects for 2 years revealed no
      significant correlation between FGF21 concentration and disease progression.
      CONCLUSIONS: Measuring FGF21 concentration had little added value in monitoring
      and predicting the disease course in this specific patient group.

PMID- 24907232
TI  - Factors associated with unfavorable outcome in minor ischemic stroke.
AB  - OBJECTIVES: The purpose of this study was to elucidate the factors that correlate
      with unfavorable outcomes and to develop a simple validated model for assessing
      risk of unfavorable outcomes in patients with minor ischemic stroke. METHODS: The
      derivation cohort included 1,313 patients hospitalized within 72 hours after
      onset with an initial NIH Stroke Scale score of 0 to 3 enrolled in a prospective,
      multicenter, observational study. Unfavorable outcome was defined as dependency
      (modified Rankin Scale score of 3-5) or death at 90 days. The predictive values
      of factors related to unfavorable outcome were evaluated. External validation was
      performed in 879 patients from a single-center stroke registry. RESULTS: In the
      derivation cohort, a total of 203 patients (15%) had unfavorable outcomes. On
      multivariable analysis, women (odds ratio [OR] 1.95, 95% confidence interval [CI]
      1.30-2.94), age >=72 years (OR 2.80, 95% CI 1.83-4.36), intra/extracranial
      vascular occlusive lesion (OR 2.80, 95% CI 1.82-4.28), leg weakness (OR 1.72, 95%
      CI 1.06-2.82), and extinction/inattention (OR 5.55, 95% CI 1.30-21.71) were
      independently associated with unfavorable outcome. Patients having both a
      vascular lesion and either leg weakness or extinction/inattention showed 4.63
      (95% CI 2.23-9.33) times the risk of unfavorable outcome compared with those
      having neither. In the validation cohort, the risk was similar, at 3.77 (95% CI
      1.64-8.37). CONCLUSIONS: Intra- and extracranial vascular imaging, NIH Stroke
      Scale items such as leg weakness and extinction/inattention, and their
      combination, as well as female sex and advanced age, may be useful for predicting
      unfavorable outcomes in patients with minor stroke.

PMID- 24907233
TI  - Improvement of internuclear ophthalmoparesis in multiple sclerosis with
      dalfampridine.

PMID- 24907234
TI  - Vascular risk and Abeta interact to reduce cortical thickness in AD vulnerable
      brain regions.
AB  - OBJECTIVE: The objective of this study was to define whether vascular risk
      factors interact with beta-amyloid (Abeta) in producing changes in brain
      structure that could underlie the increased risk of Alzheimer disease (AD).
      METHODS: Sixty-six cognitively normal and mildly impaired older individuals with
      a wide range of vascular risk factors were included in this study. The presence
      of Abeta was assessed using [(11)C]Pittsburgh compound B-PET imaging, and
      cortical thickness was measured using 3-tesla MRI. Vascular risk was measured
      with the Framingham Coronary Risk Profile Index. RESULTS: Individuals with high
      levels of vascular risk factors have thinner frontotemporal cortex independent of
      Abeta. These frontotemporal regions are also affected in individuals with Abeta
      deposition, but the latter show additional thinning in parietal cortices. Abeta
      and vascular risk were found to interact in posterior (especially in parietal)
      brain regions, where Abeta has its greatest effect. In this way, the negative
      effect of Abeta in posterior regions is increased by the presence of vascular
      risk. CONCLUSION: Abeta and vascular risk interact to enhance cortical thinning
      in posterior brain regions that are particularly vulnerable to AD. These findings
      give insight concerning the mechanisms whereby vascular risk increases the
      likelihood of developing AD and supports the therapeutic intervention of
      controlling vascular risk for the prevention of AD.

PMID- 24907235
TI  - The relationship of CPE to HIV dementia: slain by an ugly fact?

PMID- 24907237
TI  - Knowledge, attitudes and perceptions of people with type 2 diabetes as related to
      self-management practices: Results of a cross-sectional study conducted in Luzon,
      Philippines.
AB  - OBJECTIVE: This study measured factors that could be associated with self
      management practices of people with type 2 diabetes from two different health
      systems in the Philippines in terms of diabetes knowledge, attitudes, perceptions
      of support and self-efficacy, and obesity/adiposity. METHODS: Knowledge,
      attitudes, perceptions, obesity/adiposity measures, adherence to medications,
      diabetes diet, and exercise and the number of diabetes consultations of people
      with type 2 diabetes utilizing services of two different health systems were
      collected. Analysis of variance was used to determine differences in knowledge,
      attitudes, perceptions, obesity/adiposity, and demographic characteristics
      according to: proper/under-utilization of services; adherence/non-adherence to
      medications, diet and exercise; high/low perceived self-efficacy; and the health
      systems. Logistic regression was done to identify any associations with
      obesity/adiposity, self-management practices, and perceived self-efficacy.
      RESULTS: There were 549 respondents. Differences in knowledge, attitudes,
      perceptions, and some demographic characteristics between the two health systems
      and between those with high/low self-efficacy perceptions were significant.
      Perceived self-efficacy was significantly associated with all four self
      management practices. CONCLUSIONS/INTERPRETATIONS: People consulting at the
      health service with a more supportive system had better perceived self-efficacy
      and self-care behavior. Higher knowledge, attitude, and perception scores were
      noted among those with better self-efficacy perceptions, which was associated
      with better self-care behavior.

PMID- 24907238
TI  - Characterization of dysfunctional remote myocardium in left ventricular anterior
      aneurysms and improvements following surgical ventricular restoration using
      cardiac magnetic resonance imaging: preliminary results.
AB  - OBJECTIVES: In patients with previous myocardial infarction, the remote
      uninfarcted regions, although contractile, demonstrate dysfunctional wall
      kinetics because of increased afterload, which improves after surgical
      ventricular restoration (SVR). We characterized left ventricular (LV) mean
      myocardial velocity (MMV) through an analysis of endocardial motion and wall
      thickening (WT) over the cardiac cycle using standard cardiac magnetic resonance
      (cMR). METHODS: LV endocardial motion and WT from cMR data in 7 heart failure
      (HF) patients with postinfarction antero apical aneurysm were compared against
      normal controls to establish a baseline for the mean myocardial velocity during
      phases of the cardiac cycle. The HF patients' MMV and WT curves were compared
      with post-SVR data. RESULTS: Global MMV showed significant postoperative
      improvements in the ejection phase of systole and the early filling phase of
      diastole. The aneurysmal wall was dyskinetic in both systole and diastole. The
      remote myocardium preoperatively had a delayed peak velocity during the ejection
      phase of systole and diminished velocity during early filling in diastole. After
      SVR, the remote myocardium had an increased MMV with an earlier peaking during
      the ejection phase and slightly improved early diastolic velocity. WT increased
      cumulatively during systole and decreased during diastole with improved end
      systolic and end-diastolic wall thickness after SVR. The end-systolic wall
      thickness showed a significant correlation with left ventricular ejection
      fraction (r(2) = 0.89, P = 0.001) and stroke volume (r(2) = 0.80, P = 0.02). The
      MMV had a significant correlation with WT over the phases of the cardiac cycle
      (r(2) = 0.953, P <= 0.0001). CONCLUSIONS: In patients with chronic ischaemic
      heart disease with LV aneurysms/large areas of scar, improvements in the remote
      myocardial MMV and WT underline LV systolic function improvements after SVR. The
      persistence of myocardial WT in early diastole is the likely mechanism for
      incomplete or absence of relief of LV diastolic dysfunction by SVR.

PMID- 24907236
TI  - Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic
      conditions.
AB  - OBJECTIVE: The link between CNS penetration of antiretrovirals and AIDS-defining
      neurologic disorders remains largely unknown. METHODS: HIV-infected,
      antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who
      started an antiretroviral regimen were classified according to the CNS
      Penetration Effectiveness (CPE) score of their initial regimen into low (<8),
      medium (8-9), or high (>9) CPE score. We estimated "intention-to-treat" hazard
      ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE
      scores compared with regimens with a low score. We used inverse probability
      weighting to adjust for potential bias due to infrequent follow-up. RESULTS: A
      total of 61,938 individuals were followed for a median (interquartile range) of
      37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169
      cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of
      progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence
      interval) for initiating a combined antiretroviral therapy regimen with a high vs
      low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for
      toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71,
      2.47) for progressive multifocal leukoencephalopathy. The respective hazard
      ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73,
      1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). CONCLUSIONS:
      We estimated that initiation of a combined antiretroviral therapy regimen with a
      high CPE score increases the risk of HIV dementia, but not of other neuroAIDS
      conditions.

PMID- 24907240
TI  - Genes, the environment and personalized medicine: We need to harness both
      environmental and genetic data to maximize personal and population health.

PMID- 24907239
TI  - Correlations between brain structure and symptom dimensions of psychosis in
      schizophrenia, schizoaffective, and psychotic bipolar I disorders.
AB  - INTRODUCTION: Structural alterations may correlate with symptom severity in
      psychotic disorders, but the existing literature on this issue is heterogeneous.
      In addition, it is not known how cortical thickness and cortical surface area
      correlate with symptom dimensions of psychosis. METHODS: Subjects included 455
      individuals with schizophrenia, schizoaffective, or bipolar I disorders. Data
      were obtained as part of the Bipolar Schizophrenia Network for Intermediate
      Phenotypes study. Diagnosis was made through the Structured Clinical Interview
      for DSM-IV. Positive and negative symptom subscales were assessed using the
      Positive and Negative Syndrome Scale. Structural brain measurements were
      extracted from T1-weight structural MRIs using FreeSurfer v5.1 and were
      correlated with symptom subscales using partial correlations. Exploratory factor
      analysis was also used to identify factors among those regions correlating with
      symptom subscales. RESULTS: The positive symptom subscale correlated inversely
      with gray matter volume (GMV) and cortical thickness in frontal and temporal
      regions, whereas the negative symptom subscale correlated inversely with right
      frontal cortical surface area. Among regions correlating with the positive
      subscale, factor analysis identified four factors, including a temporal cortical
      thickness factor and frontal GMV factor. Among regions correlating with the
      negative subscale, factor analysis identified a frontal GMV-cortical surface area
      factor. There was no significant diagnosis by structure interactions with symptom
      severity. CONCLUSIONS: Structural measures correlate with positive and negative
      symptom severity in psychotic disorders. Cortical thickness demonstrated more
      associations with psychopathology than cortical surface area.

PMID- 24907241
TI  - Effects of nicotine administration on spectral and temporal features of
      crystallized song in the adult male zebra finch.
AB  - INTRODUCTION: The process through which the zebra finch (Taeniopygia guttata)
      acquires and produces crystallized song has long been thought of as highly
      analogous to the process through which humans acquire and produce speech.
      Nicotinic acetylcholine receptors are present in song nuclei that play important
      roles in song production and/or acquisition. We studied the effect of in vivo
      nicotine on temporal and spectral features of crystallized song. METHODS: We used
      16 adult male zebra finches that were exposed to an established 7-day nicotine or
      saline treatment. Song behavior was monitored for a 2-month period following the
      cessation of the nicotine/saline treatment. All animals served as their own
      control in order to determine whether any song characteristics changed over the
      observed time period compared to the baseline measurement. RESULTS: Inter
      syllable duration and Wiener entropy were significantly affected by the in vivo
      administration of nicotine. These observed changes persisted for a 2-month period
      following the cessation of nicotine exposure. Similar changes were not observed
      in the age-matching control group. CONCLUSIONS: Nicotine significantly affected
      tempo and rhythm of the crystallized zebra finch song. We believe that this in
      vivo nicotine-exposed zebra finch model can not only provide a further
      understanding of the underlying behavioral mechanisms of the cognitive
      implications of nicotine dependence but also help in the development of
      therapeutics targeting cognitive deficits often observed during nicotine
      withdrawal.

PMID- 24907242
TI  - Does moralization motivate smokers to quit? A longitudinal study of
      representative samples of smokers in the United States and Denmark.
AB  - INTRODUCTION: Moralization refers to the gradual cultural and personal process by
      which objects or activities move from being morally neutral to morally
      contemptuous. Research suggests important cross-cultural differences in how
      smokers react to being targets of moralization. However, research has not
      examined whether smokers who agree with moralized sentiments about smoking are
      more willing to quit or reduce their smoking. Additionally, the mediating role of
      perceived personal risk has not been examined. METHODS: In this study,
      representative samples of smokers in Denmark (a smoking lenient country; N = 429)
      and the United States (a smoking prohibitive country; N = 431) completed surveys
      6 months apart. RESULTS: As expected, Danish smokers (compared to U.S. smokers)
      moralized less and estimated that their personal risk of lung cancer was smaller.
      Furthermore, moralization at T1 predicted an increase in perceived personal risk
      at T2 (for Danish smokers and marginally for U.S. smokers), a decrease in smoking
      behaviors (for Danish smokers only), and an increase in quitting intentions
      (marginally for Danish smokers only). For Danish smokers, perceived personal risk
      mediated the relationship between moralization and quitting intentions.
      CONCLUSIONS: Moralization predicted an increase in perceived personal risk, an
      increase in quitting intentions, and a reduction in smoking behaviors, especially
      for the Danish sample. Future research should examine the effects of moralization
      in different cultural contexts.

PMID- 24907243
TI  - Study protocol for the nutritional route in oesophageal resection trial: a single
      arm feasibility trial (NUTRIENT trial).
AB  - INTRODUCTION: The best route of feeding for patients undergoing an oesophagectomy
      is unclear. Concerns exist that early oral intake would increase the incidence
      and severity of pneumonia and anastomotic leakage. However, in studies including
      patients after many other types of gastrointestinal surgery and in animal
      experiments, early oral intake has been shown to be beneficial and enhance
      recovery. Therefore, we aim to determine the feasibility of early oral intake
      after oesophagectomy. METHODS AND ANALYSIS: This study is a feasibility trial in
      which 50 consecutive patients will start oral intake directly following
      oesophagectomy. Primary outcomes will be the frequency and severity of
      anastomotic leakage and (aspiration) pneumonia. Clinical parameters will be
      registered prospectively and nutritional requirements and intake will be assessed
      by a dietician. Surgical complications will be registered. ETHICS AND
      DISSEMINATION: Approval for this study has been obtained from the Medical Ethical
      Committee of the Catharina Hospital Eindhoven and the study has been registered
      at the Dutch Trial Register, NTR4136. Results will be published and presented at
      international congresses. DISCUSSION: We hypothesise that the oral route of
      feeding is safe and feasible following oesophagectomy, as has been shown
      previously for other types of gastrointestinal surgery. It is expected that early
      oral nutrition will result in enhanced recovery. Furthermore, complications
      related to artificial feeding, such as jejunostomy tube feeding, are believed to
      be reduced. However, (aspiration) pneumonia and anastomotic leakage are potential
      risks that are carefully monitored. TRIAL REGISTRATION NUMBER: NTR4136.

PMID- 24907244
TI  - An instrument for the assessment of diarrhoeal severity based on a longitudinal
      community-based study.
AB  - OBJECTIVE: Diarrhoea is a significant contributer to morbidity and is among the
      leading causes of death of children living in poverty. As such, the incidence,
      duration and severity of diarrhoeal episodes in the household are often key
      variables of interest in a variety of community-based studies. However, there
      currently exists no means of defining diarrhoeal severity that are (A)
      specifically designed and adapted for community-based studies, (B) associated
      with poorer child outcomes and (C) agreed on by the majority of researchers.
      Clinical severity scores do exist and are used in healthcare settings, but these
      tend to focus on relatively moderate-to-severe dehydrating and dysenteric
      disease, require trained observation of the child and, given the variability of
      access and utilisation of healthcare, fail to sufficiently describe the spectrum
      of disease in the community setting. DESIGN: Longitudinal cohort study. SETTING:
      Santa Clara de Nanay, a rural community in the Northern Peruvian Amazon.
      PARTICIPANTS: 442 infants and children 0-72 months of age. MAIN OUTCOME MEASURES:
      Change in weight over 1-month intervals and change in length/height over 9-month
      intervals. RESULTS: Diarrhoeal episodes with symptoms of fever, anorexia,
      vomiting, greater number of liquid stools per day and greater number of total
      stools per day were associated with poorer weight gain compared with episodes
      without these symptoms. An instrument to measure the severity was constructed
      based on the duration of these symptoms over the course of a diarrhoeal episode.
      CONCLUSIONS: In order to address limitations of existing diarrhoeal severity
      scores in the context of community-based studies, we propose an instrument
      comprised of diarrhoea-associated symptoms easily measured by community health
      workers and based on the association of these symptoms with poorer child growth.
      This instrument can be used to test the impact of interventions on the burden of
      diarrhoeal disease.

PMID- 24907245
TI  - How weight change is modelled in population studies can affect research findings:
      empirical results from a large-scale cohort study.
AB  - OBJECTIVES: To investigate how results of the association between education and
      weight change vary when weight change is defined and modelled in different ways.
      DESIGN: Longitudinal cohort study. PARTICIPANTS: 60 404 men and women
      participating in the Social, Environmental and Economic Factors (SEEF)
      subcomponent of the 45 and Up Study-a population-based cohort study of people
      aged 45 years or older, residing in New South Wales, Australia. OUTCOME MEASURES:
      The main exposure was self-reported education, categorised into four groups. The
      outcome was annual weight change, based on change in self-reported weight between
      the 45 and Up Study baseline questionnaire and SEEF questionnaire (completed an
      average of 3.3 years later). Weight change was modelled in four different ways:
      absolute change (kg) modelled as (1) a continuous variable and (2) a categorical
      variable (loss, maintenance and gain), and relative (%) change modelled as (3) a
      continuous variable and (4) a categorical variable. Different cut-points for
      defining weight-change categories were also tested. RESULTS: When weight change
      was measured categorically, people with higher levels of education (compared with
      no school certificate) were less likely to lose or to gain weight. When weight
      change was measured as the average of a continuous measure, a null relationship
      between education and annual weight change was observed. No material differences
      in the education and weight-change relationship were found when comparing weight
      change defined as an absolute (kg) versus a relative (%) measure. Results of the
      logistic regression were sensitive to different cut-points for defining weight
      change categories. CONCLUSIONS: Using average weight change can obscure important
      directional relationship information and, where possible, categorical outcome
      measurements should be included in analyses.

PMID- 24907247
TI  - Psychiatric disorders following fetal death: a population-based cohort study.
AB  - OBJECTIVES: Women have increased risks of severe mental disorders after
      childbirth and death of a child, but it remains unclear whether this association
      also applies to fetal loss and, if so, to which extent. We studied the risk of
      any inpatient or outpatient psychiatric treatment during the time period from 12
      months before to 12 months after fetal death. DESIGN: Cohort study using Danish
      population-based registers. SETTING: Denmark. PARTICIPANTS: A total of 1 112 831
      women born in Denmark from 1960 to 1995 were included. In total, 87 687cases of
      fetal death (International Classification of Disease-10 codes for spontaneous
      abortion or stillbirth) were recorded between 1996 and 2010. PRIMARY AND
      SECONDARY OUTCOME MEASURES: The main outcome measures were incidence rate ratios
      (risk of first psychiatric inpatient or outpatient treatment). RESULTS: A total
      of 1379 women had at least one psychiatric episode during follow-up from the year
      before fetal death to the year after. Within the first few months after the loss,
      women had an increased risk of psychiatric contact, IRR: 1.51 (95% CI 1.15 to
      1.99). In comparison, no increased risk of psychiatric contact was found for the
      period before fetal death. The risk of experiencing a psychiatric episode was
      highest for women with a loss occurring after 20 weeks of gestation (12 month
      probability: 1.95%, 95% CI 1.50 to 2.39). CONCLUSIONS: Fetal death was associated
      with a transient increased risk of experiencing a first-time episode of a
      psychiatric disorder, primarily adjustment disorders. The risk of psychiatric
      episodes tended to increase with increasing gestational age at the time of the
      loss.

PMID- 24907248
TI  - Marital status and survival after oesophageal cancer surgery: a population-based
      nationwide cohort study in Sweden.
AB  - OBJECTIVES: A beneficial effect of being married on survival has been shown for
      several cancer types, but is unclear for oesophageal cancer. The objective of
      this study was to clarify the potential influence of the marital status on the
      overall and disease-specific survival after curatively intended treatment of
      oesophageal cancer using a nationwide population-based design, taking into
      account the known major prognostic variables. DESIGN: Prospective, population
      based cohort. SETTING: All Swedish hospitals performing surgery for oesophageal
      cancer during 2001-2005. PARTICIPANTS: This study included 90% of all patients
      with oesophageal or junctional cancer who underwent surgical resection in Sweden
      in 2001-2005, with follow-up until death or the end of the study period (2012).
      PRIMARY AND SECONDARY OUTCOME MEASURES: Cox regression was used to estimate
      associations between the marital status and the 5-year overall and disease
      specific mortality, expressed as HRs with 95% CIs, with adjustment for sex, age,
      tumour stage, histological type, complications, comorbidities and annual surgeon
      volume. RESULTS: Of all 606 included patients (80.4% men), 55.1% were married,
      9.2% were remarried, 22.6% were previously married and 13% were never married.
      Compared with the married patients, the never married (HR 1.02, 95% CI 0.77 to
      1.35), previously married (HR 0.90, 95% CI 0.71 to 1.15) and remarried patients
      (HR 0.79, 95% CI 0.55 to 1.13) had no increased overall 5-year mortality. The
      corresponding HRs for disease-specific survival, and after excluding the initial
      90 days of surgery, were similar to the HRs for the overall survival.
      CONCLUSIONS: This study showed no evidence of a better 5-year survival in married
      patients compared with non-married patients undergoing surgery for oesophageal
      cancer.

PMID- 24907246
TI  - Association of lifestyle-related factors with circadian onset patterns of acute
      myocardial infarction: a prospective observational study in Japan.
AB  - OBJECTIVE: The onset of acute myocardial infarction (AMI) shows characteristic
      circadian variations involving a definite morning peak and a less-defined night
      time peak. However, the factors influencing the circadian patterns of AMI onset
      and their influence on morning and night-time peaks have not been fully
      elucidated. DESIGN, SETTING AND PARTICIPANTS: An analysis of patients registered
      between 1998 and 2008 in the Osaka Acute Coronary Insufficiency Study, which is a
      prospective, multicentre observational study of patients with AMI in the Osaka
      region of Japan. The present study included 7755 consecutive patients with a
      known time of AMI onset. MAIN OUTCOMES AND MEASURES: A mixture of two von Mises
      distributions was used to examine whether a circadian pattern of AMI had uniform,
      unimodal or bimodal distribution, and the likelihood ratio test was then used to
      select the best circadian pattern among them. The hierarchical likelihood ratio
      test was used to identify factors affecting the circadian patterns of AMI onset.
      The Kaplan-Meier method was used to estimate survival curves of 1-year mortality
      according to AMI onset time. RESULTS: The overall population had a bimodal
      circadian pattern of AMI onset characterised by a high and sharp morning peak and
      a lower and less-defined night-time peak (bimodal p<0.001). Although several
      lifestyle-related factors had a statistically significant association with the
      circadian patterns of AMI onset, serum triglyceride levels had the most prominent
      association with the circadian patterns of AMI onset. Patients with triglyceride
      >=150 mg/dL on admission had only one morning peak in the circadian pattern of
      AMI onset during weekdays, with no peaks detected on weekends, whereas all other
      subgroups had two peaks throughout the week. CONCLUSIONS: The circadian pattern
      of AMI onset was characterised by bimodality. Notably, several lifestyle-related
      factors, particularly serum triglyceride levels, had a strong relation with the
      circadian pattern of AMI onset. TRIAL REGISTRATION NUMBER: UMIN000004575.

PMID- 24907250
TI  - Bending properties of a macroalga: Adaptation of Peirce's cantilever test for in
      situ measurements of Laminaria digitata (Laminariaceae).
AB  - * Premise of the study: The mechanical properties of a plant are key variables
      governing the interaction between the plant and its environment. Thus, measuring
      variables such as the flexural rigidity (bending) of a plant element is necessary
      to understand and predict the plant-flow interaction. However, plant elements
      such as macrophyte blades can be relatively thin and flexible, thus difficult to
      characterize. Different adaptations of the classical 3-point bending tests can
      also affect the interpretation of the flexural rigidity of an element. A simple,
      robust, method is newly applied to a biomaterial and validated here as an
      alternative to measure flexural rigidity of thin, flexible plant elements.*
      Methods: Based on a bending test procedure developed for the textile industry, an
      apparatus for in-situ measurements was developed and compared with other
      normalized methods, then used in a field test on the blade of a marine macroalga
      (Laminaria digitata) to assess its suitability to measure the bending modulus of
      a biomaterial.* Key results: Results of the presented method on selected
      surrogate materials agree with a normalized cantilever method (ISO 9073-7:1998)
      and 3-point bending test (ISO 178:2010). Values determined for the bending moduli
      for blades of L. digitaria were in the typical range for algal material. The
      range of validity of the method is discussed.* Conclusion: By validating this
      method with existing norms, this study suggests a better approach to measure
      bending properties of different biomaterials in the field compared with more
      traditional bending tests and opens new possibilities.

PMID- 24907251
TI  - Comparative genetic structure between Sedum ussuriense and S. kamtschaticum
      (Crassulaceae), two stonecrops co-occurring on rocky cliffs.
AB  - * Premise of the study: Geographic isolation due to discontinuities of suitable
      habitat may have significant effects on the genetic structure of plant
      populations. Even within a few kilometers, physical barriers to gene flow may
      lead to considerable genetic differentiation among populations.* Methods: Sedum
      ussuriense is a boreal species that in Korea occurs only in four valleys
      separated by mountain ranges in Juwangsan National Park and its vicinity (a range
      of ~15 km). Its congener S. kamtschaticum, by contrast, co-occurs in the four
      valleys but also on the intervening mountains. Using 12 allozyme loci, we
      comparatively assessed genetic variability and structure in 12 population pairs
      of the two stonecrops.* Key results: While we found high and comparable levels of
      within-population genetic variation for the two species, among-population
      divergence was significantly higher in S. ussuriense (FST = 0.261 vs. FST =
      0.165). Sedum ussuriense also showed a much higher percentage of among-valley
      variation (19%) than S. kamtschaticum (4%).* Conclusions: High levels of genetic
      diversity in the two Sedum species are consistent with the previous hypothesis
      that mountains of the Korean Peninsula served as glacial refugia for many boreal
      species. Given that the two congeners have similar life-history traits, the lower
      among-population differentiation in S. kamtschaticum is attributable to its
      higher abundance and more continuous distribution in the study area. This study
      confirms the central role of geographic isolation in the genetic structure of
      plant species even at very small scales.

PMID- 24907252
TI  - Cell differentiation and tissue formation in the unique fruits of devil's claws
      (Martyniaceae).
AB  - * Premise of the study: Martyniaceae are characterized by capsules with two
      upwardly curved, horn-shaped extensions representing morphologically specialized
      epizoochorous fruits. Because the capsules are assumed to cling to hooves and
      ankles of large mammals, fiber arrangement and tissue combinations within the
      endocarp ensuring proper attachment to the vector's feet during transport are of
      particular interest. In this first detailed anatomical investigation, the
      functional adaptation of the fruits and their implications for the specific
      dispersal mode are provided. The peculiar fiber arrangement may also be of
      interest for future biomimetic composite materials.* Methods: Endocarp anatomy
      and details of tissue differentiation were examined in fruits of Ibicella lutea
      and Proboscidea louisianica subsp. fragrans combining light microscopy, SEM, and
      x-ray microtomography analysis.* Key results: While tips of the extensions are
      predominantly reinforced by longitudinally oriented fibers, in the middle segment
      these fibers are densely packed in individual bundles entwined and separated by
      transversely elongated cells. Within the capsule wall, the fiber bundles are
      embedded in a dense mesh of transversely oriented fibers that circularly
      reinforce and protect the loculus. This fibrous pericarp tissue develops within
      few days by localized cell divisions and intrusive growth of primarily
      isodiametric parenchyma cells in the pistil.* Conclusions: The study allows
      insight into a unique and complex example of functionally driven cell growth and
      tissue formation. Long-horned fruits of Martyniaceae obviously are highly
      specialized to epizoochorous dispersal, pointing to primary vector-related seed
      dispersal. The highly ordered arrangement of fibers results in a great mechanical
      firmness.

PMID- 24907249
TI  - Convergent and Divergent fMRI Responses in Children and Adults to Increasing
      Language Production Demands.
AB  - In adults, patterns of neural activation associated with perhaps the most basic
      language skill--overt object naming--are extensively modulated by the
      psycholinguistic and visual complexity of the stimuli. Do children's brains react
      similarly when confronted with increasing processing demands, or they solve this
      problem in a different way? Here we scanned 37 children aged 7-13 and 19 young
      adults who performed a well-normed picture-naming task with 3 levels of
      difficulty. While neural organization for naming was largely similar in childhood
      and adulthood, adults had greater activation in all naming conditions over
      inferior temporal gyri and superior temporal gyri/supramarginal gyri.
      Manipulating naming complexity affected adults and children quite differently:
      neural activation, especially over the dorsolateral prefrontal cortex, showed
      complexity-dependent increases in adults, but complexity-dependent decreases in
      children. These represent fundamentally different responses to the linguistic and
      conceptual challenges of a simple naming task that makes no demands on literacy
      or metalinguistics. We discuss how these neural differences might result from
      different cognitive strategies used by adults and children during lexical
      retrieval/production as well as developmental changes in brain structure and
      functional connectivity.

PMID- 24907253
TI  - Speciation via floral heterochrony and presumed mycorrhizal host switching of
      endemic butterfly orchids on the Azorean archipelago.
AB  - * Premise of the study: Most orchid species native to the Macaronesian islands
      reflect immigration from western Europe or North Africa followed by anagenesis.
      The only putative exception is the butterfly orchids (Platanthera) of the Azores,
      where three species apparently reflect at least one cladogenetic speciation
      event. This multidisciplinary study explores the origin, speciation, phenotypic,
      and genotypic cohesion of these Azorean species and their mainland relatives.*
      Methods: Plants of Platanthera from 30 localities spanning all nine Azorean
      islands were compared with those of four continental European relatives for 38
      morphometric characters; substantial subsets were also analyzed for plastid
      microsatellites, and for nrITS of both the orchids and their mycorrhizae.* Key
      results: Although the three Azorean and four mainland species are all readily
      distinguished morphometrically using several floral characters, and hybridization
      appears rare, divergence in ITS and especially plastid sequences is small.
      Despite occupying similar laurisilva habitats, the Azorean species differ
      radically in the identities and diversity of their mycorrhizal partners;
      specialism apparently increases rarity.* Conclusions: Although morphological
      evidence suggests two invasions of the islands from NW Africa and/or SW Europe,
      ITS data imply only one. As the molecular data are unable to distinguish among
      the potential mainland ancestors, two scenarios of relationship are explored that
      imply different ancestors. Both scenarios require both anagenetic and
      cladogenetic speciation events, involving homoplastic shifts in overall flower
      size and (often substantial) changes in the relative dimensions of individual
      floral organs. Limited genotypic divergence among the three species compared with
      greater phenotypic divergence suggests comparatively recent speciation.
      Mycorrhizae may be the most critical factor dictating the respective ecological
      tolerances, and thus the relative frequencies, of these species. The recent IUCN
      Red-List amalgamation of Azorean Platanthera taxa into a single species urgently
      requires reappraisal, as P. micrantha is an excellent indicator species of
      seminatural laurisilva forest and P. azorica is arguably Europe's rarest orchid.

PMID- 24907254
TI  - Dynamic control of osmolality and ionic composition of the xylem sap in two
      mangrove species.
AB  - * Premise of the study: Xylem sap osmolality and salinity is a critical
      unresolved issue in plant function with impacts on transport efficiency, pressure
      gradients, and living cell turgor pressure, especially for halophytes such as
      mangrove trees.* Methods: We collected successive xylem vessel sap samples from
      stems and shoots of Avicennia germinans and Laguncularia racemosa using vacuum
      and pressure extraction and measured their osmolality. Following a series of
      extractions with the pressure chamber, we depressurized the shoot and pressurized
      again after various equilibration periods (minutes to hours) to test for dynamic
      control of osmolality. Transpiration and final sap osmolality were measured in
      shoots perfused with deionized water or different seawater dilutions.* Key
      results: For both species, the sap osmolality values of consecutive samples
      collected by vacuum extraction were stable and matched those of the initial
      samples extracted with the pressure chamber. Further extraction of samples with
      the pressure chamber decreased sap osmolality, suggesting reverse osmosis
      occurred. However, sap osmolalities increased when longer equilibration periods
      after sap extraction were allowed. Analysis of expressed sap with HPLC indicated
      a 1:1 relation between measured osmolality and the osmolality of the inorganic
      ions in the sap (mainly Na+, K+, and Cl-), suggesting no contamination by organic
      compounds. In stems perfused with deionized water, the sap osmolality increased
      to mimic the native sap osmolality.* Conclusions: Xylem sap osmolality and ionic
      contents are dynamically adjusted by mangroves and may help modulate turgor
      pressure, hydraulic conductivity, and water potential, thus being important for
      mangrove physiology, survival, and distribution.

PMID- 24907255
TI  - Demographic variation across successional stages and their effects on the
      population dynamics of the neotropical palm Euterpe precatoria.
AB  - * Premise of the study: Environmental heterogeneity is a strong selective force
      shaping adaptation and population dynamics across temporal and spatial scales.
      Natural and anthropogenic gradients influence the variation of environmental and
      biotic factors, which determine population demography and dynamics. Successional
      gradients are expected to influence demographic parameters, but the relationship
      between these gradients and the species life history, habitat requirements, and
      degree of variation in demographic traits remains elusive.* Methods: We used the
      palm Euterpe precatoria to test the effect of successional stage on plant
      demography within a continuous population. We calculated demographic parameters
      for size stages and performed matrix analyses to investigate the demographic
      variation within primary and secondary forests of La Selva, Costa Rica.* Key
      results: We observed differences in mortality and recruitment of small juveniles
      between primary and secondary forests. Matrix models described satisfactorily the
      chronosequence of population changes, which were characterized by high population
      growth rate in disturbed areas, and decreased growth rate in old successional
      forests until reaching stability.* Conclusions: Different demographic parameters
      can be expressed in contiguous subpopulations along a gradient of successional
      stages with important consequences for population dynamics. Demographic variation
      superimposed on these gradients contributes to generate subpopulations with
      different demographic composition, density, and ecological properties. Therefore,
      the effects of spatial variation must be reconsidered in the design of
      demographic analyses of tropical palms, which are prime examples of subtle local
      adaptation. These considerations are crucial in the implementation of management
      plans for palm species within spatially complex and heterogeneous tropical
      landscapes.

PMID- 24907256
TI  - Linking safe sites for recruitment with host-canopy heterogeneity: The case of a
      parasitic plant, Viscum album subsp. austriacum (Viscaceae).
AB  - * Premise of the study: Canopies are ecologically relevant compartments of
      forests. Multiple sources of heterogeneity interact within forest canopies due to
      their structural complexity, which exert major influences on the structure and
      composition of epiphyte communities. Here, we explore canopy environmental
      heterogeneity of a Mediterranean pine forest, identifying the key biotic and
      abiotic factors determining mistletoe (Viscum album subsp. austriacum)
      recruitment at coarse and fine spatial scales.* Methods: Through field
      experiments, we assessed the range of suitable host species for V. album subsp.
      austriacum (hereafter, V. a. austriacum). We characterized the variation in
      abiotic factors at a fine spatial scale on the host species. Finally, we examined
      the effects of biotic (predation) and abiotic (light, temperature) factors on the
      fate of mistletoe seeds and seedlings along host branches.* Key results: We
      confirmed the tight specificity of V. a. austriacum to pine species, in
      particular to P. nigra at the local scale. Biotic constraints increased toward
      the branch interior, with minor effects on apical locations due to the positive
      effect of pine-needle coverage. Contrarily, abiotic constraints increased toward
      branch extremities, harming mistletoe seeds by encouraging their desiccation.*
      Conclusions: Biotic and abiotic variables exert a strong, nonrandom filter on V.
      album regeneration, resulting in recruitment hotspots at the periphery of the
      branches and sites with a high probability of recruitment failure at thicker and
      more exposed locations. The narrow range of suitable host species and the
      scarcity and spatially restricted recruitment hotspots for V. a. austriacum leads
      to the clumping of mistletoe populations at the finer spatial scale.

PMID- 24907257
TI  - Different biomechanical design and ecophysiological strategies in juveniles of
      two liana species with contrasting growth habit.
AB  - * Premise of the study: Lianas constitute a major functional type in tropical
      zones. While some liana species start climbing immediately after germination
      (shade-avoidance), others have a long self-supporting phase (shade-tolerance).
      The morphophysiological characteristics of these two growth habits are unknown.*
      Methods: We quantified growth traits, biomass allocation, mechanics, anatomy, and
      hydraulics for saplings of Ventilago calyculata (an immediate obligate climber)
      and Ziziphus attopensis (having a long self-supporting phase), both in the family
      Rhamnaceae. The mechanics, anatomy, and hydraulics for the mature individuals of
      the two species were also evaluated.* Key results: In the juvenile stage, V.
      calyculata had a higher slenderness ratio, height growth rate, and photosynthetic
      rate but similar biomass growth rate compared with Z. attopensis. In contrast, Z.
      attopensis had a higher leaf area growth rate, specific leaf area, and leaf mass
      fraction. Ziziphus attopensis had stiffer, but less conductive stems than V.
      calyculata. Stem rigidity of saplings decreased from base to apex in Z.
      attopensis, but increased in V. calyculata. Both species had similar resistance
      to xylem embolism. However, the leaves of V. calyculata were able to resist
      greater water deficits. At the mature stage, wider and longer vessels emerged in
      the xylem, and both species increased stem specific conductivity and drought
      resistance in stems and leaves. Ventilago calyculata had significantly higher
      specific conductivity and was more drought tolerant than Z. attopensis.*
      Conclusions: The two lianas differed significantly in growth, biomass allocation,
      anatomy, mechanics, ecophysiology, and hydraulic properties in line with their
      growth habits and shade adaptation strategies.

PMID- 24907258
TI  - How population growth affects linkage disequilibrium.
AB  - The "LD curve" relates the linkage disequilibrium (LD) between pairs of
      nucleotide sites to the distance that separates them along the chromosome. The
      shape of this curve reflects natural selection, admixture between populations,
      and the history of population size. This article derives new results about the
      last of these effects. When a population expands in size, the LD curve grows
      steeper, and this effect is especially pronounced following a bottleneck in
      population size. When a population shrinks, the LD curve rises but remains
      relatively flat. As LD converges toward a new equilibrium, its time path may not
      be monotonic. Following an episode of growth, for example, it declines to a low
      value before rising toward the new equilibrium. These changes happen at different
      rates for different LD statistics. They are especially slow for estimates of
      [Formula: see text], which therefore allow inferences about ancient population
      history. For the human population of Europe, these results suggest a history of
      population growth. 

PMID- 24907259
TI  - Multifunctional RNA processing protein SRm160 induces apoptosis and regulates eye
      and genital development in Drosophila.
AB  - SRm160 is an SR-like protein implicated in multiple steps of RNA processing and
      nucleocytoplasmic export. Although its biochemical functions have been
      extensively described, its genetic interactions and potential participation in
      signaling pathways remain largely unknown, despite the fact that it is highly
      phosphorylated in both mammalian cells and Drosophila. To begin elucidating the
      functions of the protein in signaling and its potential role in developmental
      processes, we characterized mutant and overexpression SRm160 phenotypes in
      Drosophila and their interactions with the locus encoding the LAMMER protein
      kinase, Doa. SRm160 mutations are recessive lethal, while its overexpression
      generates phenotypes including roughened eyes and highly disorganized internal
      eye structure, which are due at least in part to aberrantly high levels of
      apoptosis. SRm160 is required for normal somatic sex determination, since its
      alleles strongly enhance a subtle sex transformation phenotype induced by Doa
      kinase alleles. Moreover, modification of SRm160 by DOA kinase appears to be
      necessary for its activity, since Doa alleles suppress phenotypes induced by
      SRm160 overexpression in the eye and enhance those in genital discs. Modification
      of SRm160 may occur through direct interaction because DOA kinase phosphorylates
      it in vitro. Remarkably, SRm160 protein was concentrated in the nuclei of
      precellular embryos but was very rapidly excluded from nuclei or degraded
      coincident with cellularization. Also of interest, transcripts are restricted
      almost exclusively to the developing nervous system in mature embryos. 

PMID- 24907260
TI  - Chromatin organization and remodeling of interstitial telomeric sites during
      meiosis in the Mongolian gerbil (Meriones unguiculatus).
AB  - Telomeric DNA repeats are key features of chromosomes that allow the maintenance
      of integrity and stability in the telomeres. However, interstitial telomere sites
      (ITSs) can also be found along the chromosomes, especially near the centromere,
      where they may appear following chromosomal rearrangements like Robertsonian
      translocations. There is no defined role for ITSs, but they are linked to DNA
      damage-prone sites. We were interested in studying the structural organization of
      ITSs during meiosis, a kind of cell division in which programmed DNA damage
      events and noticeable chromatin reorganizations occur. Here we describe the
      presence of highly amplified ITSs in the pericentromeric region of Mongolian
      gerbil (Meriones unguiculatus) chromosomes. During meiosis, ITSs show a different
      chromatin conformation than DNA repeats at telomeres, appearing more extended and
      accumulating heterochromatin markers. Interestingly, ITSs also recruit the
      telomeric proteins RAP1 and TRF1, but in a stage-dependent manner, appearing
      mainly at late prophase I stages. We did not find a specific accumulation of DNA
      repair factors to the ITSs, such as gammaH2AX or RAD51 at these stages, but we
      could detect the presence of MLH1, a marker for reciprocal recombination.
      However, contrary to previous reports, we did not find a specific accumulation of
      crossovers at ITSs. Intriguingly, some centromeric regions of metacentric
      chromosomes may bind the nuclear envelope through the association to SUN1
      protein, a feature usually performed by telomeres. Therefore, ITSs present a
      particular and dynamic chromatin configuration in meiosis, which could be
      involved in maintaining their genetic stability, but they additionally retain
      some features of distal telomeres, provided by their capability to associate to
      telomere-binding proteins. 

PMID- 24907261
TI  - The histone acetyltransferase GcnE (GCN5) plays a central role in the regulation
      of Aspergillus asexual development.
AB  - Acetylation of histones is a key regulatory mechanism of gene expression in
      eukaryotes. GcnE is an acetyltransferase of Aspergillus nidulans involved in the
      acetylation of histone H3 at lysine 9 and lysine 14. Previous works have
      demonstrated that deletion of gcnE results in defects in primary and secondary
      metabolism. Here we unveil the role of GcnE in development and show that a ?gcnE
      mutant strain has minor growth defects but is impaired in normal conidiophore
      development. No signs of conidiation were found after 3 days of incubation, and
      immature and aberrant conidiophores were found after 1 week of incubation.
      Centroid linkage clustering and principal component (PC) analysis of
      transcriptomic data suggest that GcnE occupies a central position in Aspergillus
      developmental regulation and that it is essential for inducing conidiation genes.
      GcnE function was found to be required for the acetylation of histone H3K9/K14 at
      the promoter of the master regulator of conidiation, brlA, as well as at the
      promoters of the upstream developmental regulators of conidiation flbA, flbB,
      flbC, and flbD (fluffy genes). However, analysis of the gene expression of brlA
      and the fluffy genes revealed that the lack of conidiation originated in a
      complete absence of brlA expression in the ?gcnE strain. Ectopic induction of
      brlA from a heterologous alcA promoter did not remediate the conidiation defects
      in the ?gcnE strain, suggesting that additional GcnE-mediated mechanisms must
      operate. Therefore, we conclude that GcnE is the only nonessential histone
      modifier with a strong role in fungal development found so far. 

PMID- 24907262
TI  - Extensive and biased intergenomic nonreciprocal DNA exchanges shaped a nascent
      polyploid genome, Gossypium (cotton).
AB  - Genome duplication is thought to be central to the evolution of morphological
      complexity, and some polyploids enjoy a variety of capabilities that transgress
      those of their diploid progenitors. Comparison of genomic sequences from several
      tetraploid (AtDt) Gossypium species and genotypes with putative diploid A- and D
      genome progenitor species revealed that unidirectional DNA exchanges between
      homeologous chromosomes were the predominant mechanism responsible for allelic
      differences between the Gossypium tetraploids and their diploid progenitors.
      Homeologous gene conversion events (HeGCEs) gradually subsided, declining to
      rates similar to random mutation during radiation of the polyploid into multiple
      clades and species. Despite occurring in a common nucleus, preservation of HeGCE
      is asymmetric in the two tetraploid subgenomes. At-to-Dt conversion is far more
      abundant than the reciprocal, is enriched in heterochromatin, is highly
      correlated with GC content and transposon distribution, and may silence abundant
      A-genome-derived retrotransposons. Dt-to-At conversion is abundant in euchromatin
      and genes, frequently reversing losses of gene function. The long-standing
      observation that the nonspinnable-fibered D-genome contributes to the superior
      yield and quality of tetraploid cotton fibers may be explained by accelerated Dt
      to At conversion during cotton domestication and improvement, increasing dosage
      of alleles from the spinnable-fibered A-genome. HeGCE may provide an alternative
      to (rare) reciprocal DNA exchanges between chromosomes in heterochromatin, where
      genes have approximately five times greater abundance of Dt-to-At conversion than
      does adjacent intergenic DNA. Spanning exon-to-gene-sized regions, HeGCE is a
      natural noninvasive means of gene transfer with the precision of transformation,
      potentially important in genetic improvement of many crop plants. 

PMID- 24907264
TI  - Geothermomicrobium terrae gen. nov., sp. nov., a novel member of the family
      Thermoactinomycetaceae.
AB  - Strains YIM 77562(T) and YIM 77580, two novel Gram-staining-positive, filamentous
      bacterial isolates, were recovered from the Rehai geothermal field, Tengchong,
      Yunnan province, south-west China. Good growth was observed at 50-55  degrees C
      and pH 7.0. Aerial mycelium was absent on all media tested. Substrate mycelium
      was well-developed, long and moderately flexuous, and formed abundant, single,
      warty, ornamented endospores. Phylogenetic analysis of the 16S rRNA gene
      sequences of the two strains indicated that they belong to the family
      Thermoactinomycetaceae. Similarity levels between the 16S rRNA gene sequences of
      the two strains and those of type strains of members of the
      Thermoactinomycetaceae were 88.33-93.24 %; the highest sequence similarity was
      with Hazenella coriacea DSM 45707(T). In both strains, the predominant
      menaquinone was MK-7, the diagnostic diamino acid was meso-diaminopimelic acid
      and the major cellular fatty acids were iso-C14 : 0, iso-C15 : 0 and iso-C16 : 0.
      The major polar lipids were diphosphatidylglycerol,
      phosphatidylmethylethanolamine, unidentified polar lipids and unidentified
      phospholipids. The genomic DNA G+C contents of strains YIM 77562(T) and YIM 77580
      were 45.5 and 44.2 mol%, respectively. DNA-DNA relatedness data suggest that the
      two isolates represent a single species. Based on phylogenetic analyses and
      physiological and biochemical characteristics, it is proposed that the two
      strains represent a single novel species in a new genus, Geothermomicrobium
      terrae gen. nov., sp. nov. The type strain of Geothermomicrobium terrae is YIM
      77562(T) ( = CCTCC AA 2011022(T) = JCM 18057(T)). 

PMID- 24907265
TI  - Chitinimonas prasina sp. nov., isolated from lake water.
AB  - A Gram-stain-negative, elongated rod-shaped, motile by gliding, green-pigmented,
      aerobic bacterial strain, designated LY03(T), was isolated from lake water in
      Xiamen, Fujian Province, China. Phylogenetic analysis based on 16S rRNA gene
      sequencing revealed that the isolate was a member of the genus Chitinimonas,
      which belongs to the family Burkholderiaceae. Strain LY03(T) was most closely
      related to Chitinimonas taiwanensis LMG 22011(T) (96.02 % 16S rRNA gene sequence
      similarity), followed by Chitinimonas koreensis KACC 11467(T) (94.85 %), and the
      three strains formed a distinct lineage from other strains in the phylogenetic
      analyses. Optimum conditions for growth were 37  degrees C, pH 7-9 and without
      NaCl. The major fatty acids were summed feature 3 (C16 : 1omega6c and/or C16 :
      1omega7c), C16 : 0 and C10 : 0 3-OH. The DNA G+C content of strain LY03(T) was
      63.6 mol% and the major respiratory quinone was ubiquinone-8 (Q-8). The polar
      lipids were found to consist of diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, unknown polar lipids and unidentified phospholipids.
      Differential phenotypic properties and phylogenetic distinctiveness distinguished
      strain LY03(T) from all other members of the genus Chitinimonas. On the basis of
      its morphology, physiology, fatty acid composition and 16S rRNA gene sequence
      data, strain LY03(T) represents a novel species of the genus Chitinimonas, for
      which the name Chitinimonas prasina sp. nov. is proposed. The type strain is
      LY03(T) ( = MCCC 1F01209(T) = KCTC 32574(T)). 

PMID- 24907263
TI  - Nitrososphaera viennensis gen. nov., sp. nov., an aerobic and mesophilic, ammonia
      oxidizing archaeon from soil and a member of the archaeal phylum Thaumarchaeota.
AB  - A mesophilic, neutrophilic and aerobic, ammonia-oxidizing archaeon, strain
      EN76(T), was isolated from garden soil in Vienna (Austria). Cells were irregular
      cocci with a diameter of 0.6-0.9 um and possessed archaella and archaeal pili as
      cell appendages. Electron microscopy also indicated clearly discernible areas of
      high and low electron density, as well as tubule-like structures. Strain EN76(T)
      had an S-layer with p3 symmetry, so far only reported for members of the
      Sulfolobales. Crenarchaeol was the major core lipid. The organism gained energy
      by oxidizing ammonia to nitrite aerobically, thereby fixing CO2, but growth
      depended on the addition of small amounts of organic acids. The optimal growth
      temperature was 42  degrees C and the optimal pH was 7.5, with ammonium and
      pyruvate concentrations of 2.6 and 1 mM, respectively. The genome of strain
      EN76(T) had a DNA G+C content of 52.7 mol%. Phylogenetic analyses of 16S rRNA
      genes showed that strain EN76(T) is affiliated with the recently proposed phylum
      Thaumarchaeota, sharing 85% 16S rRNA gene sequence identity with the closest
      cultivated relative 'Candidatus Nitrosopumilus maritimus' SCM1, a marine ammonia
      oxidizing archaeon, and a maximum of 81% 16S rRNA gene sequence identity with
      members of the phyla Crenarchaeota and Euryarchaeota and any of the other
      recently proposed phyla (e.g. 'Korarchaeota' and 'Aigarchaeota'). We propose the
      name Nitrososphaera viennensis gen. nov., sp. nov. to accommodate strain EN76(T).
      The type strain of Nitrososphaera viennensis is strain EN76(T) ( = DSM 26422(T) =
      JMC 19564(T)). Additionally, we propose the family Nitrososphaeraceae fam. nov.,
      the order Nitrososphaerales ord. nov. and the class Nitrososphaeria classis nov.

PMID- 24907267
TI  - GSTT1 polymorphism and the risk of developing prostate cancer.
AB  - A possible association between glutathione S-transferase theta 1 gene (GSTT1)
      polymorphism and the risk of developing prostate cancer is currently hotly
      debated, but evidence from various epidemiologic studies remains unclear. This
      investigation was performed to assess whether an association between GSTT1
      polymorphism and prostate cancer risk exists by using meta-analysis to combine
      comparable studies, thereby increasing sample size and statistical significance,
      as well as to identify patterns in various studies. The association reports were
      identified from the PubMed database and the Cochrane Library on March 1, 2013,
      and data from eligible studies (from 1999-2012) were synthesized. Thirty-eight
      reports were included in this meta-analysis on the association of the null
      genotype of GSTT1 with prostate cancer risk. No solid association between the
      GSTT1 null genotype and prostate cancer risk could be established for the overall
      population (odds ratio = 1.11, 95% confidence interval: 0.97, 1.27; P = 0.13).
      However, the GSTT1 null genotype was distinctly associated with prostate cancer
      risk in Caucasians (odds ratio = 1.24, 95% confidence interval: 1.03, 1.48, P =
      0.02). In conclusion, the GSTT1 null genotype is associated with prostate cancer
      risk in Caucasians, but not in the overall population. 

PMID- 24907266
TI  - Description of Domibacillus indicus sp. nov., isolated from ocean sediments and
      emended description of the genus Domibacillus.
AB  - A novel Gram-stain-positive, spore-forming, aerobic, non-motile, rod-shaped
      bacterium designated strain SD111(T) that forms red-pigmented colonies was
      isolated from a marine sediment sample (collected from 5 m depth) from
      Lakshadweep, India. Strain SD111(T) grew well on seawater agar at pH 6-10
      (optimum pH 7.5+/-0.2). It showed maximum (97.6 %) 16S rRNA gene sequence
      similarity and formed a monophyletic clade with Domibacillus robiginosus WS
      4628(T) ( = DSM 25058(T)). The genomic DNA G+C content was 37.4 mol% and the
      strain showed 37.7 % DNA-DNA relatedness to D. robiginosus DSM 25058(T). The
      major fatty acids were anteiso-C15 : 0, C16 : 0, iso-C15 : 0 and iso-C16 : 0 and
      MK-6 was the predominant quinone. The polar lipid profile of strain SD111(T)
      consisted of unidentified phospholipids (PL1 and PL2), phosphatidylglycerol (PG)
      and diphosphatidylglycerol (DPG). The cell wall contained meso-diaminopimelic
      acid and the peptidoglycan was of A1gamma type. Glucose and ribose were detected
      as major cell-wall sugars. Results from polyphasic studies indicated that
      SD111(T) represents a novel species of the genus Domibacillus for which the name
      Domibacillus indicus sp. nov. is proposed. The type strain is SD111(T) ( = MCC
      2255(T) = DSM 28032(T)). 

PMID- 24907271
TI  - beta-site amyloid precursor protein cleaving enzyme 1(BACE1) regulates Notch
      signaling by controlling the cleavage of Jagged 1 (Jag1) and Jagged 2 (Jag2)
      proteins.
AB  - BACE1 is a type I transmembrane aspartyl protease that cleaves amyloid precursor
      protein at the beta-secretase site to initiate the release of beta-amyloid
      peptide. As a secretase, BACE1 also cleaves additional membrane-bound molecules
      by exerting various cellular functions. In this study, we showed that BACE1 can
      effectively shed the membrane-anchored signaling molecule Jagged 1 (Jag1).Wealso
      mapped the cleavage sites of Jag1 by ADAM10 and ADAM17. Although Jag1 shares a
      high degree of homology with Jag2 in the ectodomain region, BACE1 fails to cleave
      Jag2 effectively, indicating a selective cleavage of Jag1. Abolished cleavage of
      Jag1 in BACE1-null mice leads to enhanced astrogenesis and, concomitantly,
      reduced neurogenesis. This characterization provides biochemical evidence that
      the Jag1-Notch pathway is under the control of BACE1 activity

PMID- 24907272
TI  - An arginine-rich motif of ring finger protein 4 (RNF4) oversees the recruitment
      and degradation of the phosphorylated and SUMOylated Kruppel-associated box
      domain-associated protein 1 (KAP1)/TRIM28 protein during genotoxic stress.
AB  - Kruppel-associated box domain-associated protein 1 (KAP1) is a universal
      transcriptional corepressor that undergoes multiple posttranslational
      modifications (PTMs), including SUMOylation and Ser-824 phosphorylation. However,
      the functional interplay of KAP1 PTMs in regulating KAP1 turnover during DNA
      damage response remains unclear. To decipher the role and cross-talk of multiple
      KAP1 PTMs, we show here that DNA double strand break-induced KAP1 Ser-824
      phosphorylation promoted the recruitment of small ubiquitin-like modifier (SUMO)
      targeted ubiquitin E3 ligase, ring finger protein 4 (RNF4), and subsequent RNF4
      mediated, SUMO-dependent degradation. Besides the SUMO interacting motif (SIM), a
      previously unrecognized, but evolutionarily conserved, arginine-rich motif (ARM)
      in RNF4 acts as a novel recognition motif for selective target recruitment.
      Results from combined mutagenesis and computational modeling studies suggest that
      RNF4 utilizes concerted bimodular recognition, namely SIM for Lys-676 SUMOylation
      and ARM for Ser(P)-824 of simultaneously phosphorylated and SUMOylated KAP1
      (Ser(P)-824-SUMO-KAP1). Furthermore, we proved that arginines 73 and 74 within
      the ARM of RNF4 are required for efficient recruitment to KAP1 or accelerated
      degradation of promyelocytic leukemia protein (PML) under stress. In parallel,
      results of bimolecular fluorescence complementation assays validated the role of
      the ARM in recognizing Ser(P)-824 in living cells. Taken together, we establish
      that the ARM is required for RNF4 to efficiently target Ser(P)-824-SUMO-KAP1,
      conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of
      double strand breaks. The conservation of such a motif may possibly explain the
      requirement for timely substrate selectivity determination among a myriad of
      SUMOylated proteins under stress conditions. Thus, the ARM dynamically regulates
      the SIM-dependent recruitment of targets to RNF4, which could be critical to
      dynamically fine-tune the abundance of Ser(P)-824-SUMO-KAP1 and, potentially,
      other SUMOylated proteins during DNA damage response. 

PMID- 24907273
TI  - Characterization of genomic deletion efficiency mediated by clustered regularly
      interspaced short palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian
      cells.
AB  - The clustered regularly interspaced short  [corrected] palindromic repeats
      (CRISPR)/CRISPR-associated (Cas) 9 nuclease system has provided a powerful tool
      for genome engineering. Double strand breaks may trigger nonhomologous end
      joining repair, leading to frameshift mutations, or homology-directed repair
      using an extrachromosomal template. Alternatively, genomic deletions may be
      produced by a pair of double strand breaks. The efficiency of CRISPR/Cas9
      mediated genomic deletions has not been systematically explored. Here, we present
      a methodology for the production of deletions in mammalian cells, ranging from
      1.3 kb to greater than 1 Mb. We observed a high frequency of intended genomic
      deletions. Nondeleted alleles are nonetheless often edited with inversions or
      small insertion/deletions produced at CRISPR recognition sites. Deleted alleles
      also typically include small insertion/deletions at predicted deletion junctions.
      We retrieved cells with biallelic deletion at a frequency exceeding that of
      probabilistic expectation. We demonstrate an inverse relationship between
      deletion frequency and deletion size. This work suggests that CRISPR/Cas9 is a
      robust system to produce a spectrum of genomic deletions to allow investigation
      of genes and genetic elements.

PMID- 24907274
TI  - Allosteric activation of Bordetella pertussis adenylyl cyclase by calmodulin:
      molecular dynamics and mutagenesis studies.
AB  - Adenylyl cyclase (AC) toxin is an essential toxin that allows Bordetella
      pertussis to invade eukaryotic cells, where it is activated after binding to
      calmodulin (CaM). Based on the crystal structure of the AC catalytic domain in
      complex with the C-terminal half of CaM (C-CaM), our previous molecular dynamics
      simulations (Selwa, E., Laine, E., and Malliavin, T. (2012) Differential role of
      calmodulin and calcium ions in the stabilization of the catalytic domain of
      adenyl cyclase CyaA from Bordetella pertussis. Proteins 80, 1028-1040) suggested
      that three residues (i.e. Arg(338), Asn(347), and Asp(360)) might be important
      for stabilizing the AC/CaM interaction. These residues belong to a loop-helix
      loop motif at the C-terminal end of AC, which is located at the interface between
      CaM and the AC catalytic loop. In the present study, we conducted the in silico
      and in vitro characterization of three AC variants, where one (Asn(347); ACm1A),
      two (Arg(338) and Asp(360); ACm2A), or three residues (Arg(338), Asn(347), and
      Asp(360); ACm3A) were substituted with Ala. Biochemical studies showed that the
      affinities of ACm1A and ACm2A for CaM were not affected significantly, whereas
      that of ACm3A was reduced dramatically. To understand the effects of these
      modifications, molecular dynamics simulations were performed based on the
      modified proteins. The molecular dynamics trajectories recorded for the ACm3AC
      CaM complex showed that the calcium-binding loops of C-CaM exhibited large
      fluctuations, which could be related to the weakened interaction between ACm3A
      and its activator. Overall, our results suggest that the loop-helix-loop motif at
      the C-terminal end of AC is crucial during CaM binding for stabilizing the AC
      catalytic loop in an active configuration.

PMID- 24907275
TI  - Mutation of threonine 34 in mouse podoplanin-Fc reduces CLEC-2 binding and
      toxicity in vivo while retaining antilymphangiogenic activity.
AB  - The lymphatic system plays an important role in cancer metastasis and inhibition
      of lymphangiogenesis could be valuable in fighting cancer dissemination.
      Podoplanin (Pdpn) is a small, transmembrane glycoprotein expressed on the surface
      of lymphatic endothelial cells (LEC). During mouse development, binding of Pdpn
      to the C-type lectin-like receptor 2 (CLEC-2) on platelets is critical for the
      separation of the lymphatic and blood vascular systems. Competitive inhibition of
      Pdpn functions with a soluble form of the protein, Pdpn-Fc, leads to reduced
      lymphangiogenesis in vitro and in vivo. However, the transgenic overexpression of
      human Pdpn-Fc in mouse skin causes disseminated intravascular coagulation due to
      platelet activation via CLEC-2. In the present study, we produced and
      characterized a mutant form of mouse Pdpn-Fc, in which threonine 34, which is
      considered essential for CLEC-2 binding, was mutated to alanine (PdpnT34A-Fc).
      Indeed, PdpnT34A-Fc displayed a 30-fold reduced binding affinity for CLEC-2
      compared with Pdpn-Fc. This also translated into fewer side effects due to
      platelet activation in vivo. Mice showed less prolonged bleeding time and fewer
      embolized vessels in the liver, when PdpnT34A-Fc was injected intravenously.
      However, PdpnT34A-Fc was still as active as wild-type Pdpn-Fc in inhibiting
      lymphangiogenesis in vitro and also inhibited lymphangiogenesis in vivo. These
      data suggest that the function of Pdpn in lymphangiogenesis does not depend on
      threonine 34 in the CLEC-2 binding domain and that PdpnT34A-Fc might be an
      improved inhibitor of lymphangiogenesis with fewer toxic side effects.

PMID- 24907276
TI  - The kinetics underlying the velocity of smooth muscle myosin filament sliding on
      actin filaments in vitro.
AB  - Actin-myosin interactions are well studied using soluble myosin fragments, but
      little is known about effects of myosin filament structure on mechanochemistry.
      We stabilized unphosphorylated smooth muscle myosin (SMM) and phosphorylated
      smooth muscle myosin (pSMM) filaments against ATP-induced depolymerization using
      a cross-linker and attached fluorescent rhodamine (XL-Rh-SMM). Electron
      micrographs showed that these side polar filaments are very similar to unmodified
      filaments. They are ~0.63 MUm long and contain ~176 molecules. Rate constants for
      ATP-induced dissociation and ADP release from acto-myosin for filaments and S1
      heads were similar. Actin-activated ATPases of SMM and XL-Rh-SMM were similarly
      regulated. XL-Rh-pSMM filaments moved processively on F-actin that was bound to a
      PEG brush surface. ATP dependence of filament velocities was similar to that for
      solution ATPases at high [actin], suggesting that both processes are limited by
      the same kinetic step (weak to strong transition) and therefore are attachment-
      limited. This differs from actin sliding over myosin monomers, which is primarily
      detachment-limited. Fitting filament data to an attachment-limited model showed
      that approximately half of the heads are available to move the filament,
      consistent with a side polar structure. We suggest the low stiffness subfragment
      2 (S2) domain remains unhindered during filament motion in our assay. Actin-bound
      negatively displaced heads will impart minimal drag force because of S2 buckling.
      Given the ADP release rate, the velocity, and the length of S2, these heads will
      detach from actin before slack is taken up into a backwardly displaced high
      stiffness position. This mechanism explains the lack of detachment- limited
      kinetics at physiological [ATP]. These findings address how nonlinear elasticity
      in assemblies of motors leads to efficient collective force generation.

PMID- 24907277
TI  - Pathway-selective insulin resistance and metabolic disease: the importance of
      nutrient flux.
AB  - Hepatic glucose and lipid metabolism are altered in metabolic disease (e.g.
      obesity, metabolic syndrome, and Type 2 diabetes). Insulin-dependent regulation
      of glucose metabolism is impaired. In contrast, lipogenesis,
      hypertriglyceridemia, and hepatic steatosis are increased. Because insulin
      promotes lipogenesis and liver fat accumulation, to explain the elevation in
      plasma and tissue lipids, investigators have suggested the presence of pathway
      selective insulin resistance. In this model, insulin signaling to glucose
      metabolism is impaired, but insulin signaling to lipid metabolism is intact. We
      discuss the evidence for the differential regulation of hepatic lipid and glucose
      metabolism. We suggest that the primary phenotypic driver is altered substrate
      delivery to the liver, as well as the repartitioning of hepatic nutrient
      handling. Specific alterations in insulin signaling serve to amplify the
      alterations in hepatic substrate metabolism. Thus, hyperinsulinemia and its
      resultant increased signaling may facilitate lipogenesis, but are not the major
      drivers of the phenotype of pathway-selective insulin resistance.

PMID- 24907279
TI  - Drivers of inequality in disability-free expectancy at birth and age 85 across
      space and time in Great Britain.
AB  - BACKGROUND: Although mortality and health inequalities at birth have increased
      both geographically and in socioeconomic terms, little is known about
      inequalities at age 85, the fastest growing sector of the population in Great
      Britain (GB). AIM: To determine whether trends and drivers of inequalities in
      life expectancy (LE) and disability-free life expectancy (DFLE) at age 85 between
      1991 and 2001 are the same as those at birth. METHODS: DFLE at birth and age 85
      for 1991 and 2001 by gender were calculated for each local authority in GB using
      the Sullivan method. Regression modelling was used to identify area
      characteristics (rurality, deprivation, social class composition, ethnicity,
      unemployment, retirement migration) that could explain inequalities in LE and
      DFLE. RESULTS: Similar to values at birth, LE and DFLE at age 85 both increased
      between 1991 and 2001 (though DFLE increased less than LE) and gaps across local
      areas widened (and more for DFLE than LE). The significantly greater increases in
      LE and DFLE at birth for less-deprived compared with more-deprived areas were
      still partly present at age 85. Considering all factors, inequalities in DFLE at
      birth were largely driven by social class composition and unemployment rate, but
      these associations appear to be less influential at age 85. CONCLUSIONS:
      Inequalities between areas in LE and DFLE at birth and age 85 have increased over
      time though factors explaining inequalities at birth (mainly social class and
      unemployment rates) appear less important for inequalities at age 85.

PMID- 24907278
TI  - How epigallocatechin gallate can inhibit alpha-synuclein oligomer toxicity in
      vitro.
AB  - Oligomeric species of various proteins are linked to the pathogenesis of
      different neurodegenerative disorders. Consequently, there is intense focus on
      the discovery of novel inhibitors, e.g. small molecules and antibodies, to
      inhibit the formation and block the toxicity of oligomers. In Parkinson disease,
      the protein alpha-synuclein (alphaSN) forms cytotoxic oligomers. The flavonoid
      epigallocatechin gallate (EGCG) has previously been shown to redirect the
      aggregation of alphaSN monomers and remodel alphaSN amyloid fibrils into
      disordered oligomers. Here, we dissect EGCG's mechanism of action. EGCG inhibits
      the ability of preformed oligomers to permeabilize vesicles and induce
      cytotoxicity in a rat brain cell line. However, EGCG does not affect oligomer
      size distribution or secondary structure. Rather, EGCG immobilizes the C-terminal
      region and moderately reduces the degree of binding of oligomers to membranes. We
      interpret our data to mean that the oligomer acts by destabilizing the membrane
      rather than by direct pore formation. This suggests that reduction (but not
      complete abolition) of the membrane affinity of the oligomer is sufficient to
      prevent cytotoxicity. 

PMID- 24907280
TI  - Prospective longitudinal cohort questionnaire assessment of labouring women's
      preference both pre- and post-delivery for either reduced pain intensity for a
      longer duration or greater pain intensity for a shorter duration.
AB  - BACKGROUND: Assessments of labour pain focus on pain intensity, not on duration.
      We aimed to assess the importance labouring women apply to pain intensity and
      duration before labour and post-delivery. METHODS: Forty healthy women scheduled
      for labour induction were enrolled in this institutional review board-approved,
      prospective cohort study. Participants completed a pain preference questionnaire
      before active labour and within 24-h of delivery. The questionnaire consisted of
      seven stem questions that evaluated preference for pain intensity or duration.
      The pain preference ratio was determined by dividing the percentage of women who
      preferred reduced pain intensity for longer duration by that of those who
      preferred greater pain intensity for shorter duration (estimate of the odds). The
      overall hypothetical pain burden was determined by multiplying intensity by time.
      All questions presented the same overall hypothetical pain burden. RESULTS: Pain
      preference questionnaire scores demonstrated preference for low intensity pain
      for a longer duration rather than higher intensity for a shorter duration, both
      pre-labour (P<0.001) and post-delivery (P<0.001): the null median imputed as 3 of
      6 (i.e. no preference for pain intensity over pain duration). This preference for
      pain duration over intensity was greater post-delivery compared with before
      labour (P=0.03). There was a significant correlation (r=0.83; P=0.04) between the
      pain preference ratio vs overall hypothetical pain burden before labour but not
      after delivery (r=0.28; P=0.59). CONCLUSIONS: In this preliminary labour
      assessment, women preferred lower pain intensity at the cost of longer pain
      duration. This suggests that pain intensity is the primary driver of hypothetical
      pain burden-a preference reinforced post-delivery.

PMID- 24907282
TI  - Dexamethasone and peripheral nerve blocks: on the nerve or intravenous?

PMID- 24907281
TI  - Risk factors for obstetric morbidity in patients with uterine atony undergoing
      caesarean delivery.
AB  - BACKGROUND: Uterine atony (UA) is recognized as a leading cause of postpartum
      haemorrhage. However, knowledge of risk factors of haemorrhage-related morbidity
      among patients diagnosed with UA is uncertain. We investigated risk factors for
      haemorrhage-related morbidity among patients undergoing Caesarean delivery with
      UA. METHODS: We conducted a secondary analysis of data sourced from a 4-yr
      observational study at 19 US academic centres. Patients with UA were identified
      based on receiving methylergonovine or carboprost. Our primary outcome
      (haemorrhage-related morbidity) included a composite of intra- or postpartum
      transfusion; Caesarean hysterectomy; uterine or hypogastric artery ligation;
      intensive care admission for: pulmonary oedema, coagulopathy, adult respiratory
      distress syndrome, postoperative ventilation, or invasive line monitoring.
      RESULTS: Among 57,182 patients who underwent Caesarean delivery, 2294 (4%)
      patients developed UA. Haemorrhage-related morbidity occurred in 450 (19.6%)
      patients with UA. The risk of haemorrhage-related morbidity was increased among
      African-Americans [adjusted odds ratio (aOR)=2.36; 95% confidence interval
      (CI)=1.73-3.23], Hispanics (aOR=1.4; 95% CI=1.04-1.9), women with multiple
      gestations (aOR=1.59; 95% CI=1.06-2.38), placenta praevia (aOR=4.89; 95% CI=3.04
      7.87), patients with ASA class III (aOR=1.4; 95 CI=1.03-1.9), or ASA class IV
      (aOR=5.88; 95% CI=2.48-13.9), exposure to general anaesthesia (GA) (aOR=2.4; 95%
      CI=1.59-3.62) and combined general and regional anaesthesia (aOR=4.0; 95% CI=2.62
      6.09), and >=2 prior Caesarean deliveries (aOR=1.62; 95% CI=1.1-2.39).
      CONCLUSIONS: Among patients with UA undergoing Caesarean delivery, the risk of
      haemorrhage-related morbidity is increased in African-Americans, Hispanics,
      patients with multiple gestations, placenta praevia, ASA class III or IV, >=2
      prior Caesarean deliveries and those undergoing GA.

PMID- 24907283
TI  - Regional anaesthesia to improve pain outcomes in paediatric surgical patients: a
      qualitative systematic review of randomized controlled trials.
AB  - Summary The development of analgesic interventions in paediatric surgical
      patients is often limited by the inherent difficulties of conducting large
      randomized clinical trials to test interventions in those patients. Regional
      anaesthesia is a valid strategy to improve postoperative pain in the adult
      surgical population, but the effects of regional anaesthesia on postoperative
      pain outcomes in paediatric patients are currently not well defined. The main
      objective of the current review was to systematically evaluate the use of
      regional anaesthesia techniques to minimize postoperative pain in paediatric
      patients. A systematic search was performed to identify randomized controlled
      trials that evaluated the effects of the regional anaesthesia techniques on
      postoperative pain outcomes in paediatric surgical patients' procedures. Seventy
      three studies on 5125 paediatric patients were evaluated. Only few surgical
      procedures had more than one small randomized controlled trial favouring the use
      of regional anaesthesia to minimize postoperative pain (ophthalmological surgery,
      cleft lip repair, inguinal hernia, and urological procedures). Additional
      evidence is required to support the use of specific regional anaesthesia
      techniques to improve postoperative pain for several surgical procedures
      (craniectomy, adenotonsillectomy, appendectomy, cardiac surgery, umbilical hernia
      repair, upper and lower extremity) in paediatric patients. Currently, only a very
      limited number of regional anaesthesia techniques have demonstrated significant
      improvement on postoperative pain outcomes for a restricted number of surgical
      procedures. More studies are needed in order to establish regional anaesthesia as
      a valid strategy to improve analgesia in the paediatric surgical population. 

PMID- 24907284
TI  - Methane yield phenotypes linked to differential gene expression in the sheep
      rumen microbiome.
AB  - Ruminant livestock represent the single largest anthropogenic source of the
      potent greenhouse gas methane, which is generated by methanogenic archaea
      residing in ruminant digestive tracts. While differences between individual
      animals of the same breed in the amount of methane produced have been observed,
      the basis for this variation remains to be elucidated. To explore the mechanistic
      basis of this methane production, we measured methane yields from 22 sheep, which
      revealed that methane yields are a reproducible, quantitative trait. Deep
      metagenomic and metatranscriptomic sequencing demonstrated a similar abundance of
      methanogens and methanogenesis pathway genes in high and low methane emitters.
      However, transcription of methanogenesis pathway genes was substantially
      increased in sheep with high methane yields. These results identify a discrete
      set of rumen methanogens whose methanogenesis pathway transcription profiles
      correlate with methane yields and provide new targets for CH4 mitigation at the
      levels of microbiota composition and transcriptional regulation. 

PMID- 24907286
TI  - Examination of the Test-Retest Reliability of a Computerized Neurocognitive Test
      Battery.
AB  - BACKGROUND: Test-retest reliability is a critical issue in the utility of
      computer-based neurocognitive assessment paradigms employing baseline and
      postconcussion tests. Researchers have reported low test-retest reliability for
      the Immediate Post Concussion Assessment and Cognitive Testing (ImPACT) across an
      interval of 45 and 50 days. PURPOSE: To re-examine the test-retest reliability of
      the ImPACT between baseline, 45 days, and 50 days. STUDY DESIGN: Descriptive
      laboratory study. METHODS: Eighty-five physically active college students (51
      male, 34 female) volunteered for this study. Participants completed the ImPACT as
      well as a 15-item memory test at baseline, 45 days, and 50 days. Intraclass
      correlation coefficients (ICCs) were calculated for ImPACT composite scores, and
      change scores were calculated using reliable change indices (RCIs) and regression
      based methods (RBMs) at 80% and 95% confidence intervals (CIs). RESULTS: The
      respective ICCs for baseline to day 45, day 45 to day 50, baseline to day 50, and
      overall were as follows: verbal memory (0.76, 0.69, 0.65, and 0.78), visual
      memory (0.72, 0.66, 0.60, and 0.74), visual motor (processing) speed (0.87, 0.88,
      0.85, and 0.91), and reaction time (0.67, 0.81, 0.71, and 0.80). All ICCs
      exceeded the threshold value of 0.60 for acceptable test-retest reliability. All
      cases fell well within the 80% CI for both the RCI and RBM, while 1% to 5% of
      cases fell outside the 95% CI for the RCI and 1% for the RBM. CONCLUSION: Results
      suggest that the ImPACT is a reliable neurocognitive test battery at 45 and 50
      days after the baseline assessment. The current findings agree with those of
      other reliability studies that have reported acceptable ICCs across 30-day to 1
      year testing intervals, and they support the utility of the ImPACT for the
      multidisciplinary approach to concussion management. CLINICAL RELEVANCE: This
      study suggests that the computerized neurocognitive test battery, ImPACT, is a
      reliable test for postconcussion serial assessments. However, when managing
      concussed athletes, the ImPACT should not be used as a stand-alone measure.

PMID- 24907287
TI  - Osteochondral Autologous Transplantation Is Superior to Repeat Arthroscopy for
      the Treatment of Osteochondral Lesions of the Talus After Failed Primary
      Arthroscopic Treatment.
AB  - BACKGROUND: Several studies have reported on the outcome of arthroscopic
      treatment or osteochondral autologous transplantation (OAT) for osteochondral
      lesions of the talus (OLT), with mixed results. None of these studies has
      compared the results of repeat arthroscopy and OAT after failed primary
      arthroscopic treatment. PURPOSE: To compare the outcomes of OAT and repeat
      arthroscopy for the treatment of OLT after primary arthroscopy STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: This study included 22 patients who
      underwent OAT (group A) and 22 patients who underwent repeat arthroscopy (group
      B) after failed treatment of OLT among 399 patients who received primary
      arthroscopic marrow stimulation at single institution between 2001 and 2009. All
      patients were evaluated clinically using the visual analog scale (VAS) for pain
      and American Orthopaedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Scale. The
      cumulative success rates were compared by use of Kaplan-Meier life table
      analysis. RESULTS: The patients' demographic and clinical characteristics and
      indications for surgery were comparable between the groups. Both groups showed
      significantly improved (P < .001) VAS and AOFAS scores 6 months after surgery.
      However, group B showed significant deterioration over a mean follow-up period of
      50 months. Overall, 18 of 22 (81.8%) patients in group A and 7 of 22 (31.8%)
      patients in group B achieved an excellent or good (>=80) AOFAS score (P < .001).
      No patient in group A and 14 of 22 (63.6%) in group B required further revisions.
      CONCLUSION: Osteochondral autologous transplantation was significantly superior
      to repeat arthroscopic treatment of OLT after a mean follow-up period of 48
      months. Therefore, repeat arthroscopy should be used judiciously for the
      treatment of OLT after failed arthroscopic treatment.

PMID- 24907285
TI  - Physical activity, obesity, weight change, and risk of atrial fibrillation: the
      Atherosclerosis Risk in Communities study.
AB  - BACKGROUND: Physical activity (PA) has previously been suggested to attenuate the
      risk of atrial fibrillation (AF) conferred by excess body weight and weight gain.
      We prospectively examined the relationship between body size, weight change, and
      level of PA in a biracial cohort of middle-aged men and women. METHODS AND
      RESULTS: Baseline characteristics on risk factor levels were obtained on 14 219
      participants from the Atherosclerosis Risk in Communities Study. AF incidence was
      ascertained from 1987 to 2009. Adjusted Cox proportional hazards models were used
      to estimate the associations between body mass index, waist circumference,
      relative weight change, and PA level with incident AF. During follow-up, there
      were 1775 cases of incident AF. Body mass index and waist circumference were
      positively associated with AF as was weight loss/gain of >5% initial body weight.
      An ideal level of PA had a small protective effect on AF risk and partially
      attenuated the risk of AF associated with excess weight in men but not women:
      compared with men with a normal body mass index, the risk of AF in obese men with
      an ideal, intermediate, and poor level of PA at baseline was increased by 37%,
      129%, and 156% (Pinteraction=0.04). During follow-up, PA did not modify the
      association between weight gain and risk of AF. CONCLUSIONS: Obesity and extreme
      weight change are risk factors for incident AF, whereas being physically active
      is associated with a small reduction in risk. In men only, being physically
      active offset some, but not all, of the risk incurred with excess body weight.

PMID- 24907288
TI  - Talking with parents of high school football players about chronic traumatic
      encephalopathy: a concise summary.
AB  - Over the past decade, athletic-related chronic traumatic encephalopathy (CTE) has
      garnered a great deal of attention in the popular press and, more recently, in
      the scientific press. With increasing frequency, sports medicine practitioners
      and providers are faced with questions from the parents of high school football
      players about CTE and the risk posed to children who participate in this or other
      contact or collision sports. The purpose of this review was to summarize the
      research on CTE in an attempt to provide some evidence-based answers to
      frequently asked questions in clinics from parents. Addressed are (1) the
      definitions of CTE and its symptoms, (2) the evidence for CTE in football, (3)
      abnormal tau protein, (4) the use of neuroimaging in CTE diagnosis, (5) risk for
      CTE, (6) CTE diagnosis in youth, (7) CTE and its relationship to suicide, and (8)
      contact and collision sports as a risk factor for permanent brain injury or
      death. 

PMID- 24907289
TI  - Prevalence and Incidence of Cartilage Injuries and Meniscus Tears in Patients Who
      Underwent Both Primary and Revision Anterior Cruciate Ligament Reconstructions.
AB  - BACKGROUND: Previous studies have found differences in meniscus and cartilage
      injury rates between groups of patients after primary and revision anterior
      cruciate ligament reconstructions (ACLRs). This study examined a cohort of
      individual patients who underwent primary and subsequent revision ACLR to
      determine the incidence of cartilage and meniscus disease. PURPOSE: To describe
      the prevalence and incidence of meniscus and articular cartilage injuries in
      patients who underwent primary and then subsequent revision ACLR as well as
      indicate differences in the management of these injuries. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Patients who underwent primary and then
      revision ACLR from February 2005 to September 2011 were identified using a
      community-based registry. Patient and procedure characteristics were obtained,
      and descriptive statistics were used to evaluate the study sample. RESULTS: There
      were 261 patients who underwent primary and then subsequent revision ACLR during
      the study period. The median age was 18 years at primary ACLR and 20 years at
      revision ACLR. Revision ACLR was performed for instability in 256 patients (98%)
      and for infection in 5 patients (2%). The prevalence of cartilage injuries
      increased from 14.9% at primary ACLR to 31.8% at revision ACLR. The prevalence of
      meniscus tears decreased from 54.8% at primary ACLR to 43.7% at revision ACLR.
      The prevalence of lateral meniscus tears was 32.2% at primary ACLR but only 18.4%
      at revision ACLR, while the prevalence of medial meniscus tears was the same at
      primary and revision ACLRs (32.6%). Patients who underwent meniscus tear
      treatment at primary ACLR had a 70.8% prevalence of meniscus tears at revision
      ACLR. CONCLUSION: In this community-based sample followed from primary ACLR to
      revision ACLR, the prevalence of articular cartilage injuries increased, while
      the prevalence of meniscus injuries decreased. The higher prevalence of articular
      cartilage injuries at revision ACLR may represent new injuries. The lower
      prevalence of meniscus tears at revision ACLR may be caused by susceptible
      menisci being injured and treated at primary surgery or by changes in knee
      kinematics or injury exposure patterns.

PMID- 24907291
TI  - In memoriam: Roy K Greenberg.

PMID- 24907290
TI  - Long-term follow-up shows excellent transmural atrial lead performance in
      patients with complex congenital heart disease.
AB  - BACKGROUND: Many patients with congenital heart disease require permanent pacing
      for rhythm management but cannot undergo transvenous lead placement. In others,
      epicardial scarring prohibits adequate sensing and pacing thresholds using
      epicardial leads. This study describes long-term lead performance using a
      transmural atrial (epicardial to endocardial) pacing approach in patients with
      congenital heart disease. METHODS AND RESULTS: For transmural atrial (TMA) lead
      access, a bipolar, steroid-eluting transvenous lead was placed from the
      epicardium via purse-string incision or atriotomy and affixed to atrial
      endocardium. Records were reviewed for patient data and acute and long-term lead
      performance for TMA leads placed 1998 to 2004. Forty-two of 48 TMA leads remain
      active at last follow-up. Two leads fractured, 4 were functional at >5-year
      follow-up but no longer active. Freedom from lead failure 98% (95% confidence
      interval, 86%-100%) at mean follow-up 7.8 years. TMA leads gave excellent sensing
      and pacing characteristics at implant and chronically. Median acute and chronic
      sensing thresholds were 3 and 2.8 mV, respectively; median acute and chronic
      pacing thresholds at 0.5 ms were 0.9 and 0.7 V, respectively. TMA leads performed
      similarly in Fontan patients. Overdrive pacing for intra-atrial re-entrant
      tachycardia was successful in 7 of 8 patients. One patient with high baseline
      risk died of stroke 7 years after implant. No lead-associated thrombi were
      observed. CONCLUSIONS: TMA pacing leads had excellent longevity, initial, and
      chronic functional properties and provide an alternative to epicardial leads in
      patients with congenital heart disease. Patients who cannot receive transvenous
      leads, have epicardial scarring or have intra-atrial re-entrant tachycardia could
      benefit most from routine use of this technique.

PMID- 24907292
TI  - Animal models of atherosclerosis and magnetic resonance imaging for monitoring
      plaque progression.
AB  - Atherosclerosis, the main cause of heart attack and stroke, is the leading cause
      of death in most modern countries. Preventing clinical events depends on a better
      understanding of the mechanism of atherosclerotic plaque destabilization. Our
      knowledge on the characteristics of vulnerable plaques in humans has grown past
      decades. Histological studies have provided a precise definition of high-risk
      lesions and novel imaging methods for human atherosclerotic plaque
      characterization have made significant progress. However the pathological
      mechanisms leading from stable lesions to the formation of vulnerable plaques
      remain uncertain and the related clinical events are unpredictable. An animal
      model mimicking human plaque destablization is required as well as an in vivo
      imaging method to assess and monitor atherosclerosis progression. Magnetic
      resonance imaging (MRI) is increasingly used for in vivo assessment of
      atherosclerotic plaques in the human carotids. MRI provides well-characterized
      morphological and functional features of human atherosclerotic plaque which can
      be also assessed in animal models. This review summarizes the most common species
      used as animal models for experimental atherosclerosis, the techniques to induce
      atherosclerosis and to obtain vulnerable plaques, together with the role of MRI
      for monitoring atherosclerotic plaques in animals.

PMID- 24907293
TI  - Chylomicrons produced by Caco-2 cells contained ApoB-48 with diameter of 80-200
      nm.
AB  - The small intestine generally transports dietary fats to circulation in
      triglyceride (TG)-rich lipoproteins. The two main intestinal lipoproteins are
      chylomicron (CM) and very low-density lipoprotein (VLDL). Unfortunately, studies
      on the CM biogenesis and intestinal transport of dietary fats have been hampered
      by the lack of an adequate in vitro model. In this study, we investigated the
      possible factors that might increase the efficiency of CM production by Caco-2
      cells. We utilized sequential NaCl gradient ultracentrifugation to isolate the
      CMs that were secreted by the Caco-2 cells. To confirm the successful isolation
      of the CMs, we performed Fat Red 7B staining, TG reading, apolipoprotein B (ApoB)
      measurement, and transmission electron microcopy (TEM) analysis. We then tested
      the effects of cell differentiation, oleic acid, mono-olein, egg lecithin,
      incubation time, and collagen matrix on CM secretion. We found that cell
      differentiation, oleic acid, and lecithin were critical for CM secretion. Using
      the Transwell system, we further confirmed that the CMs produced by our Caco-2
      cells contained significant amount of TGs and ApoB-48 such that they could be
      detected without the use of isotope labeling. In conclusion, when fully
      differentiated Caco-2 were challenged with oleic acid, lecithin, and sodium
      taurocholate, 21% of their total number of lipoproteins were CMs with the
      diameter of 80-200 nm. 

PMID- 24907294
TI  - Startle evoked movement is delayed in older adults: implications for brainstem
      processing in the elderly.
AB  - Little attention has been given to how age affects the neural processing of
      movement within the brainstem. Since the brainstem plays a critical role in motor
      control throughout the whole body, having a clear understanding of deficits in
      brainstem function could provide important insights into movement deficits in
      older adults. A unique property of the startle reflex is its ability to
      involuntarily elicit planned movements, a phenomenon referred to as startReact.
      The noninvasive startReact response has previously been used to probe both
      brainstem utilization and motor planning. Our objective was to evaluate deficits
      in startReact hand extension movements in older adults. We hypothesized that
      startReact hand extension will be intact but delayed. Electromyography was
      recorded from the sternocleidomastoid (SCM) muscle to detect startle and the
      extensor digitorum communis (EDC) to quantify movement onset in both young (24 +/
      1) and older adults (70 +/- 11). Subjects were exposed to a startling loud sound
      when prepared to extend their hand. Trials were split into those where a startle
      did (SCM+) and did not (SCM-) occur. We found that startReact was intact but
      delayed in older adults. SCM+ onset latencies were faster than SCM- trials in
      both the populations, however, SCM+ onset latencies were slower in older adults
      compared to young (Delta = 8 msec). We conclude that the observed age-related
      delay in the startReact response most likely arises from central processing
      delays within the brainstem. 

PMID- 24907295
TI  - The effects of aging on the functional and structural properties of the rat
      basilar artery.
AB  - Aging leads to progressive pathophysiological changes in blood vessels of the
      brain and periphery. The aim of this study was to evaluate the effects of aging
      on cerebral vascular function and structure. Basilar arteries were isolated from
      male Fischer 344 cross Brown Norway (F344xBN) rats at 3, 8, and 24 months of age.
      The basilar arteries were cannulated in the pressurized system (90 cm H2O).
      Contractile responses to KCl (30-120 mmol/L) and endothelin-1 (10(-11)-10(-7)
      mol/L) were evaluated. Responses to acetylcholine (ACh) (10(-10)-10(-4) mol/L),
      diethylamine (DEA)-NONO-ate (10(-10)-10(-4) mol/L), and papaverin (10(-10)-10(-4)
      mol/L) were assessed to determine both endothelium-dependent and endothelium
      independent responsiveness. Advanced aging (24 months) decreased responses of the
      basilar artery to both the contractile and relaxing agents; whereas, DEA-induced
      dilation was significantly higher in the 8-month-old group compared with the
      younger and older groups. The arterial wall-to-lumen ratio was significantly
      increased in 24-month-old rats. Smooth muscle cell count was also decreased in
      old rats. These findings indicate that aging produces dysfunction of both the
      endothelium and the vascular smooth muscle in the basilar artery. Aging also
      alters wall structure of the basilar artery, possibly through decreases in smooth
      muscle cell number and concomitant hypertrophy. 

PMID- 24907296
TI  - Forearm vasodilator responses to a beta-adrenergic receptor agonist in
      premenopausal and postmenopausal women.
AB  - Beta-adrenergic vasodilator responses may be blunted in humans who are at an
      increased risk for hypertension. Because menopause is associated with an increase
      in blood pressure, we tested the hypothesis that forearm blood flow responses to
      the beta-adrenergic receptor agonist isoproterenol are blunted in older,
      postmenopausal women compared to young, premenopausal women. We used venous
      occlusion plethysmography to measure forearm blood flow in young premenopausal
      (26 +/- 1 years; n = 13) and postmenopausal (61 +/- 2 years; n = 12) women.
      Forearm blood flow and mean arterial pressure were measured at baseline and
      during isoproterenol infusion at 1.0, 3.0, 6.0, and 12.0 ng/100 mL tissue/min.
      The two groups did not differ in body mass index or mean arterial pressure.
      Baseline forearm blood flow was similar between young and postmenopausal women
      (3.7 +/- 0.5 vs. 2.9 +/- 0.4 mL/100 mL tissue/min, respectively; P > 0.05). At
      the lowest dose of isoproterenol, forearm blood flow vasodilator responses were
      lower in postmenopausal women compared with young women (5.8 +/- 0.4 vs. 7.4 +/-
      0.3 mL/100 mL tissue/min, respectively; P < 0.05). Thereafter, forearm blood flow
      remained similar between the groups for the remaining isoproterenol doses. In
      conclusion, beta-adrenergic receptor-mediated forearm vasodilator responses are
      blunted in healthy, older postmenopausal women at lower but not higher doses of
      isoproterenol. This suggests that in aging women, beta-adrenergic receptor
      mediated vasodilator responses may be blunted at a moderate level of stimulation
      while maximum receptor responses are preserved. 

PMID- 24907297
TI  - Effects of systemic hypoxia on human muscular adaptations to resistance exercise
      training.
AB  - Hypoxia is an important modulator of endurance exercise-induced oxidative
      adaptations in skeletal muscle. However, whether hypoxia affects resistance
      exercise-induced muscle adaptations remains unknown. Here, we determined the
      effect of resistance exercise training under systemic hypoxia on muscular
      adaptations known to occur following both resistance and endurance exercise
      training, including muscle cross-sectional area (CSA), one-repetition maximum
      (1RM), muscular endurance, and makers of mitochondrial biogenesis and
      angiogenesis, such as peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha (PGC-1alpha), citrate synthase (CS) activity, nitric oxide
      synthase (NOS), vascular endothelial growth factor (VEGF), hypoxia-inducible
      factor-1 (HIF-1), and capillary-to-fiber ratio. Sixteen healthy male subjects
      were randomly assigned to either a normoxic resistance training group (NRT, n =
      7) or a hypoxic (14.4% oxygen) resistance training group (HRT, n = 9) and
      performed 8 weeks of resistance training. Blood and muscle biopsy samples were
      obtained before and after training. After training muscle CSA of the femoral
      region, 1RM for bench-press and leg-press, muscular endurance, and skeletal
      muscle VEGF protein levels significantly increased in both groups. The increase
      in muscular endurance was significantly higher in the HRT group. Plasma VEGF
      concentration and skeletal muscle capillary-to-fiber ratio were significantly
      higher in the HRT group than the NRT group following training. Our results
      suggest that, in addition to increases in muscle size and strength, HRT may also
      lead to increased muscular endurance and the promotion of angiogenesis in
      skeletal muscle. 

PMID- 24907298
TI  - Essential role of vesicular nucleotide transporter in vesicular storage and
      release of nucleotides in platelets.
AB  - Nucleotides are stored in the dense granules of platelets. The release of
      nucleotides triggers one of the first steps in a series of cascades responsible
      for blood coagulation. However, the mechanism of how the nucleotides are
      accumulated in the granules is still far less understood. The transporter protein
      responsible for storage of nucleotides in the neuroendocrine cells has been
      identified and characterized. We hypothesized that the vesicular nucleotide
      transporter (VNUT) is also involved in the vesicular storage of nucleotides in
      platelets. In this article, we present three lines of evidence that VNUT is
      responsible for the vesicular storage of nucleotides in platelets and that
      vesicular ATP transport is crucial for platelet function, detection and
      characterization of VNUT activity in platelets isolated from healthy humans and
      MEG-01 cells, RNA interference experiments on MEG-01 cells, and studies on
      nucleotide transport and release with a selective inhibitor. 

PMID- 24907299
TI  - Hindlimb venous distention evokes a pressor reflex in decerebrated rats.
AB  - The distention of small vessels caused by an increase in blood flow to
      dynamically exercising muscles has been proposed as a stimulus that activates the
      thin fiber (groups III and IV) afferents evoking the exercise pressor reflex.
      This theory has been supported by evidence obtained from both humans and animals.
      In decerebrated unanesthetized rats with either freely perfused femoral arteries
      or arteries that were ligated 3 days before the experiment, we attempted to
      provide evidence in support of this theory by measuring arterial pressure, heart
      rate, and renal sympathetic nerve discharge while retrogradely injecting Ringer's
      solution in increasing volumes into the femoral vein just as it excited the
      triceps surae muscles. We found that the pressor response to injection was
      directly proportional to the volume injected. Retrograde injection of volumes up
      to and including 1 mL had no significant effect on either heart rate or renal
      sympathetic nerve activity. Cyclooxygenase blockade with indomethacin attenuated
      the reflex pressor response to retrograde injection in both groups of rats. In
      contrast, gadolinium, which blocks mechanogated channels, attenuated the reflex
      pressor response to retrograde injection in the "ligated rats," but had no effect
      on the response in "freely perfused" rats. Our findings are consistent with the
      possibility that distension of small vessels within exercising skeletal muscle
      can serve as a stimulus to the thin fiber afferents evoking the exercise pressor
      reflex. 

PMID- 24907300
TI  - Leukocyte margination at arteriole shear rate.
AB  - We numerically investigated margination of leukocytes at arteriole shear rate in
      straight circular channels with diameters ranging from 10 to 22 MUm. Our results
      demonstrated that passing motion of RBCs effectively induces leukocyte
      margination not only in small channels but also in large channels. A longer time
      is needed for margination to occur in a larger channel, but once a leukocyte has
      marginated, passing motion of RBCs occurs continuously independent of the channel
      diameter, and leukocyte margination is sustained for a long duration. We also
      show that leukocytes rarely approach the wall surface to within a microvillus
      length at arteriole shear rate. 

PMID- 24907301
TI  - Routine screening for alpha-thalassaemia using an immunochromatographic strip
      assay for haemoglobin Bart's.
AB  - OBJECTIVE: To evaluate an immunochromatographic (IC) strip assay for Hb Bart's as
      a routine screening test for alpha-thalassaemia in area with a high prevalence of
      thalassaemia and haemoglobinopathies. METHODS: A total of 300 adult screen
      positive blood specimens were collected at an ongoing thalassaemia screening
      programme in northeast Thailand. Routine screening was done using red blood cell
      indices, osmotic fragility, and dichlorophenolindophenol tests. The IC strip
      assay for haemoglobin Bart's was performed on all samples. The result was
      evaluated against thalassaemia genotypes determined using standard haemoglobin
      and DNA analyses. RESULTS: Of 300 subjects investigated, Hb and DNA analyses
      identified 32 with normal genotype. The remaining subjects carried thalassaemia
      with as many as 16 different genotypes. Hb Bart's was detected in all cases, with
      several alpha(0)-thalassaemia (SEA type) related disorders. Of cases with
      alpha(+)-thalassaemia, 86.1% showed a positive result; 100 out of 103 Hb E
      carriers, all homozygous Hb E and beta-thalassaemia trait were negative. Nine out
      of 17 cases with beta-thalassaemia/Hb E disease, and one case of double
      heterozygote for Hb Q-Thailand and Hb E returned positive results. The overall
      sensitivity and specificity of the IC strip assay for detecting alpha(0)
      thalassaemia were 100% and 73.1%, respectively. CONCLUSION: The results showed a
      high sensitivity for screening for alpha(0)-thalassaemia using IC strip assay for
      Hb Bart's. This simple method, used in combination with conventional screening
      protocols, should lead to a significant reduction in the number of referral cases
      for DNA analysis. Cost effectiveness in each population should be taken into
      consideration.

PMID- 24907303
TI  - Less is more: minimal expression of myoendothelial gap junctions optimizes cell
      cell communication in virtual arterioles.
AB  - Dysfunctional electrical signalling within the arteriolar wall is a major cause
      of cardiovascular disease. The endothelial cell layer constitutes the primary
      electrical pathway, co-ordinating contraction of the overlying smooth muscle cell
      (SMC) layer. As myoendothelial gap junctions (MEGJs) provide direct contact
      between the cell layers, proper vasomotor responses are thought to depend on a
      high, uniform MEGJ density. However, MEGJs are observed to be expressed
      heterogeneously within and among vascular beds. This discrepancy is addressed in
      the present study. As no direct measures of MEGJ conductance exist, we employed a
      computational modelling approach to vary the number, conductance and distribution
      of MEGJs. Our simulations demonstrate that a minimal number of randomly
      distributed MEGJs augment arteriolar cell-cell communication by increasing
      conduction efficiency and ensuring appropriate membrane potential responses in
      SMCs. We show that electrical coupling between SMCs must be tailored to the
      particular MEGJ distribution. Finally, observation of non-decaying mechanical
      conduction in arterioles without regeneration has been a long-standing
      controversy in the microvascular field. As heterogeneous MEGJ distributions
      provide for different conduction profiles along the cell layers, we demonstrate
      that a non-decaying conduction profile is possible in the SMC layer of a vessel
      with passive electrical properties. These intriguing findings redefine the
      concept of efficient electrical communication in the microcirculation,
      illustrating how heterogeneous properties, ubiquitous in biological systems, may
      have a profound impact on system behaviour and how acute local and global flow
      control is explained from the biophysical foundations. 

PMID- 24907302
TI  - Developmental changes in Ca2+ channel subtypes regulating endocytosis at the
      calyx of Held.
AB  - At the mammalian central synapse, Ca(2+) influx through Ca(2+) channels triggers
      neurotransmitter release by exocytosis of synaptic vesicles, which fuse with the
      presynaptic membrane and are subsequently retrieved by endocytosis. At the calyx
      of Held terminal, P/Q-type Ca(2+) channels mainly mediate exocytosis, while N-
      and R-type channels have a minor role in young terminals (postnatal days 8-11).
      The role of each Ca(2+) channel subtype in endocytosis remains to be elucidated;
      therefore, we examined the role of each type of Ca(2+) channel in endocytosis, by
      using whole-cell patch-clamp recordings in conjunction with capacitance
      measurement techniques. We found that at the young calyx terminal, when R-type
      Ca(2+) channels were blocked, the slow mode of endocytosis was further slowed,
      while blocking of either P/Q- or N-type Ca(2+) channels had no major effect. In
      more mature terminals (postnatal days 14-17), the slow mode of endocytosis was
      mainly triggered by P/Q-type Ca(2+) channels, suggesting developmental changes in
      the regulation of the slow mode of endocytosis by different Ca(2+) channel
      subtypes. In contrast, a fast mode of endocytosis was observed after strong
      stimulation in young terminals that was mediated mainly by P/Q-type, but not R-
      or N-type Ca(2+) channels. These results suggest that different types of Ca(2+)
      channels regulate the two different modes of endocytosis. The results may also
      suggest that exo- and endocytosis are regulated independently at different sites
      in young animals but are more tightly coupled in older animals, allowing more
      efficient synaptic vesicle cycling adapted for fast signalling. 

PMID- 24907304
TI  - Depression biased non-Hebbian spike-timing-dependent synaptic plasticity in the
      rat subiculum.
AB  - The subiculum is a structure that forms a bridge between the hippocampus and the
      entorhinal cortex (EC), and plays a major role in the memory consolidation
      process. Here, we demonstrate spike-timing-dependent plasticity (STDP) at the
      proximal excitatory inputs on the subicular pyramidal neurons of juvenile rat.
      Causal (positive) pairing of a single EPSP with a single back-propagating action
      potential (bAP) after a time interval of 10 ms (+10 ms) failed to induce
      plasticity. However, increasing the number of bAPs in a burst to three, at two
      different frequencies of 50 Hz (bAP burst) and 150 Hz, induced long-term
      depression (LTD) after a time interval of +10 ms in both the regular-firing (RF),
      and the weak burst firing (WBF) neurons. The LTD amplitude decreased with
      increasing time interval between the EPSP and the bAP burst. Reversing the order
      of the pairing of the EPSP and the bAP burst induced LTP at a time interval of 
      10 ms. This finding is in contrast with reports at other synapses, wherein pre-
      before postsynaptic (causal) pairing induced LTP and vice versa. Our results
      reaffirm the earlier observations that the relative timing of the pre- and
      postsynaptic activities can lead to multiple types of plasticity profiles. The
      induction of timing-dependent LTD (t-LTD) was dependent on postsynaptic calcium
      change via NMDA receptors in the WBF neurons, while it was independent of
      postsynaptic calcium change, but required active L-type calcium channels in the
      RF neurons. Thus the mechanism of synaptic plasticity may vary within a
      hippocampal subfield depending on the postsynaptic neuron involved. This study
      also reports a novel mechanism of LTD induction, where L-type calcium channels
      are involved in a presynaptically induced synaptic plasticity. The findings may
      have strong implications in the memory consolidation process owing to the central
      role of the subiculum and LTD in this process. 

PMID- 24907307
TI  - Nutrient-induced changes in the phenotype and function of the enteric nervous
      system.
AB  - The enteric nervous system (ENS) integrates numerous sensory signals in order to
      control and maintain normal gut functions. Nutrients are one of the prominent
      factors which determine the chemical milieu in the lumen and, after absorption,
      also within the gut wall. This review summarizes current knowledge on the impact
      of key nutrients on ENS functions and phenotype, covering their acute and long
      term effects. Enteric neurones contain the molecular machinery to respond
      specifically to nutrients. These transporters and receptors are not expressed
      exclusively in the ENS but are also present in other cells such as
      enteroendocrine cells (EECs) and extrinsic sensory nerves, signalling satiety or
      hunger. Glucose, amino acids and fatty acids all activate enteric neurones, as
      suggested by enhanced c-Fos expression or spike discharge. These excitatory
      effects are the result of a direct neuronal activation but also involve the
      activation of EECs which, upon activation by luminal nutrients, release mediators
      such as ghrelin, cholecystokinin or serotonin. The presence or absence of
      nutrients in the intestinal lumen induces long-term changes in neurotransmitter
      expression, excitability, neuronal survival and ultimately impact upon gut
      motility, secretion or intestinal permeability. Together with EECs and vagal
      nerves, the ENS must be recognized as an important player initiating concerted
      responses to nutrients. It remains to be studied how, for instance, nutrient
      induced changes in the ENS may influence additional gut functions such as
      intestinal barrier repair, intestinal epithelial stem cell
      proliferation/differentiation and also the signalling of extrinsic nerves to
      brain regions which control food intake. 

PMID- 24907306
TI  - Diabetic kidney disease: from physiology to therapeutics.
AB  - Diabetic kidney disease (DKD) defines the functional, structural and clinical
      abnormalities of the kidneys that are caused by diabetes. This complication has
      become the single most frequent cause of end-stage renal disease. The
      pathophysiology of DKD comprises the interaction of both genetic and
      environmental determinants that trigger a complex network of pathophysiological
      events, which leads to the damage of the glomerular filtration barrier, a highly
      specialized structure formed by the fenestrated endothelium, the glomerular
      basement membrane and the epithelial podocytes, that permits a highly selective
      ultrafiltration of the blood plasma. DKD evolves gradually over years through
      five progressive stages. Briefly they are: reversible glomerular hyperfiltration,
      normal glomerular filtration and normoalbuminuria, normal glomerular filtration
      and microalbuminuria, macroalbuminuria, and renal failure. Approximately 20-40%
      of diabetic patients develop microalbuminuria within 10-15 years of the diagnosis
      of diabetes, and about 80-90% of those with microalbuminuria progress to more
      advanced stages. Thus, after 15-20 years, macroalbuminuria occurs approximately
      in 20-40% of patients, and around half of them will present renal insufficiency
      within 5 years. The screening and early diagnosis of DKD is based on the
      measurement of urinary albumin excretion and the detection of microalbuminuria,
      the first clinical sign of DKD. The management of DKD is based on the general
      recommendations in the treatment of patients with diabetes, including optimal
      glycaemic and blood pressure control, adequate lipid management and abolishing
      smoking, in addition to the lowering of albuminuria.

PMID- 24907308
TI  - Hearing in noisy environments: noise invariance and contrast gain control.
AB  - Contrast gain control has recently been identified as a fundamental property of
      the auditory system. Electrophysiological recordings in ferrets have shown that
      neurons continuously adjust their gain (their sensitivity to change in sound
      level) in response to the contrast of sounds that are heard. At the level of the
      auditory cortex, these gain changes partly compensate for changes in sound
      contrast. This means that sounds which are structurally similar, but have
      different contrasts, have similar neuronal representations in the auditory
      cortex. As a result, the cortical representation is relatively invariant to
      stimulus contrast and robust to the presence of noise in the stimulus. In the
      inferior colliculus (an important subcortical auditory structure), gain changes
      are less reliably compensatory, suggesting that contrast- and noise-invariant
      representations are constructed gradually as one ascends the auditory pathway. In
      addition to noise invariance, contrast gain control provides a variety of
      computational advantages over static neuronal representations; it makes efficient
      use of neuronal dynamic range, may contribute to redundancy-reducing, sparse
      codes for sound and allows for simpler decoding of population responses. The
      circuits underlying auditory contrast gain control are still under investigation.
      As in the visual system, these circuits may be modulated by factors other than
      stimulus contrast, forming a potential neural substrate for mediating the effects
      of attention as well as interactions between the senses. 

PMID- 24907309
TI  - Cardiorenal syndrome: acute kidney injury secondary to cardiovascular disease and
      role of protein-bound uraemic toxins.
AB  - Cardiovascular disease (CVD) and kidney disease are closely interrelated. Disease
      of one organ can induce dysfunction of the other, ultimately leading to failure
      of both. Clinical awareness of synergistic adverse clinical outcomes in patients
      with coexisting CVD and kidney disease or 'cardiorenal syndrome (CRS)' has
      existed. Renal dysfunction, even mild, is a strong independent predictor for poor
      prognosis in CVD patients. Developing therapeutic interventions targeting acute
      kidney injury (AKI) has been limited due mainly to lack of effective tools to
      accurately detect AKI in a timely manner. Neutrophil gelatinase-associated
      lipocalin and kidney injury molecule-1 have been recently demonstrated to be
      potential candidate biomarkers in patients undergoing cardiac surgery. However,
      further validation of AKI biomarkers is needed in other CVD settings, especially
      acute decompensated heart failure and acute myocardial infarction where AKI
      commonly occurs. The other concern with regard to understanding the pathogenesis
      of renal complications in CVD is that mechanistically oriented studies have been
      relatively rare. Pre-clininal studies have shown that activation of renal
      inflammation-fibrosis processes, probably triggered by haemodynamic derangement,
      underlies CVD-associated renal dysfunction. On the other hand, it is postulated
      that there still are missing links in the heart-kidney connection in CRS patients
      who have significant renal dysfunction. At present, non-dialysable protein-bound
      uraemic toxins (PBUTs) appear to be the main focus in this regard. Evidence of
      the causal role of PBUTs in CRS has been increasingly demonstrated, mainly
      focusing on indoxyl sulfate (IS) and p-cresyl sulfate (pCS). Both IS and pCS are
      derived from colonic microbiotic metabolism of dietary amino acids, and hence the
      colon has become a target of treatment in addition to efforts to improve dialysis
      techniques for better removal of PBUTs. Novel therapy targeting the site of toxin
      production has led to new prospects in early intervention for predialysis
      patients with chronic kidney disease.

PMID- 24907310
TI  - SUMO1 enhances cAMP-dependent exocytosis and glucagon secretion from pancreatic
      alpha-cells.
AB  - Post-translational modification by the small ubiquitin-like modifier-1 (SUMO1)
      limits insulin secretion from beta-cells by inhibiting insulin exocytosis and
      glucagon-like peptide-1 (GLP-1) receptor signalling. The secretion of glucagon
      from alpha-cells is regulated in a manner opposite to that of insulin; it is
      inhibited by elevated glucose and GLP-1, and increased by adrenergic signalling.
      We therefore sought to determine whether SUMO1 modulates mouse and human alpha
      cell function. Action potentials (APs), ion channel function and exocytosis in
      single alpha-cells from mice and humans, identified by glucagon immunostaining,
      and glucagon secretion from intact islets were measured. The effects of SUMO1 on
      alpha-cell function and the respective inhibitory and stimulatory effects of
      exendin 4 and adrenaline were examined. Upregulation of SUMO1 increased alpha
      cell AP duration, frequency and amplitude, in part as a result of increased
      Ca(2+) channel activity that led to elevated exocytosis. The ability of SUMO1 to
      enhance alpha-cell exocytosis was cAMP-dependent and resulted from an increased L
      type Ca(2+) current and a shift away from exocytosis dependent on non-L-type
      channels, an effect that was mimicked by knockdown of the deSUMOylating enzyme
      sentrin/SUMO-specific protease-1 (SENP1). Finally, although SUMO1 prevented GLP-1
      receptor-mediated inhibition of alpha-cell Na(+) channels and single-cell
      exocytosis, it failed to prevent the exendin 4-mediated inhibition of glucagon
      secretion. Consistent with its cAMP dependence, however, SUMO1 enhanced alpha
      cell exocytosis and glucagon secretion stimulated by adrenaline. Thus, by
      contrast with its inhibitory role in beta-cell exocytosis, SUMO1 is a positive
      regulator of alpha-cell exocytosis and glucagon secretion under conditions of
      elevated cAMP. 

PMID- 24907312
TI  - Clinical and microscopic characteristics of canine toxic epidermal necrolysis.
AB  - Canine toxic epidermal necrosis (TEN), a rare and life-threatening cutaneous drug
      reaction, traditionally has been described as full-thickness devitalization of
      the epidermis with minimal dermal inflammation; however, few reports detail the
      histologic findings. We characterize the clinical features and histologic
      variations of 3 canine TEN patients. Clinically, irregular erythematous and
      purpuric macules evolved into widespread and severely painful erosions. The
      number of eroded mucosae varied; however, periocular and perilabial mucocutaneous
      junctions frequently were affected. Thirteen of 17 biopsies were evaluated.
      Apoptosis at multiple epidermal levels was the most common pattern of epidermal
      necrosis (12/13 biopsies, 92%). In contrast, full-thickness coagulation necrosis
      was present less often (7/13 biopsies, 52%). Lymphocytic interface dermatitis was
      the predominant inflammatory pattern, and intraepidermal lymphocytes, along with
      fewer histiocytes, were present to some degree in all samples along with
      lymphocytic satellitosis of apoptotic keratinocytes. The sequence of changes
      points to lymphocyte-mediated keratinocyte apoptosis as an early step in lesion
      development with subsequent variation in progression to coagulation necrosis
      among patients. Histopathologic changes overlapped with those reported for
      erythema multiforme, in contrast to traditional histologic descriptions of canine
      TEN. A specific algorithm for assessment of drug causality in epidermal
      necrolysis (ALDEN) was applied for each patient; carprofen was associated with a
      probable score for causality in 1 dog. Clinicians should be encouraged to take
      multiple biopsies in TEN suspect cases as nearly 25% of all biopsies lacked
      epithelium and were not diagnostic. 

PMID- 24907311
TI  - Transcranial cerebellar direct current stimulation and transcutaneous spinal cord
      direct current stimulation as innovative tools for neuroscientists.
AB  - Two neuromodulatory techniques based on applying direct current (DC) non
      invasively through the skin, transcranial cerebellar direct current stimulation
      (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes
      consistent with a direct influence on the human cerebellum and spinal cord. In
      this article we review the major experimental works on cerebellar tDCS and on
      spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS
      modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour,
      and cognition (learning, language, memory, attention). Spinal tDCS influences the
      ascending and descending spinal pathways, and spinal reflex excitability. In the
      anaesthetised mouse, DC stimulation applied under the skin along the entire
      spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical
      studies in patients with cerebellar disorders, and in animals and patients with
      spinal cord injuries, have reported beneficial effects. Overall the available
      data show that cerebellar tDCS and spinal tDCS are two novel approaches for
      inducing prolonged functional changes and neuroplasticity in the human cerebellum
      and spinal cord, and both are new tools for experimental and clinical
      neuroscientists. 

PMID- 24907313
TI  - What is the most prominent factor limiting photosynthesis in different layers of
      a greenhouse cucumber canopy?
AB  - BACKGROUND AND AIMS: Maximizing photosynthesis at the canopy level is important
      for enhancing crop yield, and this requires insights into the limiting factors of
      photosynthesis. Using greenhouse cucumber (Cucumis sativus) as an example, this
      study provides a novel approach to quantify different components of
      photosynthetic limitations at the leaf level and to upscale these limitations to
      different canopy layers and the whole plant. METHODS: A static virtual three
      dimensional canopy structure was constructed using digitized plant data in
      GroIMP. Light interception of the leaves was simulated by a ray-tracer and used
      to compute leaf photosynthesis. Different components of photosynthetic
      limitations, namely stomatal (S(L)), mesophyll (M(L)), biochemical (B(L)) and
      light (L(L)) limitations, were calculated by a quantitative limitation analysis
      of photosynthesis under different light regimes. KEY RESULTS: In the virtual
      cucumber canopy, B(L) and L(L) were the most prominent factors limiting whole
      plant photosynthesis. Diffusional limitations (S(L) + M(L)) contributed <15% to
      total limitation. Photosynthesis in the lower canopy was more limited by the
      biochemical capacity, and the upper canopy was more sensitive to light than other
      canopy parts. Although leaves in the upper canopy received more light, their
      photosynthesis was more light restricted than in the leaves of the lower canopy,
      especially when the light condition above the canopy was poor. An increase in
      whole-plant photosynthesis under diffuse light did not result from an improvement
      of light use efficiency but from an increase in light interception. Diffuse light
      increased the photosynthesis of leaves that were directly shaded by other leaves
      in the canopy by up to 55%. CONCLUSIONS: Based on the results, maintaining
      biochemical capacity of the middle-lower canopy and increasing the leaf area of
      the upper canopy would be promising strategies to improve canopy photosynthesis
      in a high-wire cucumber cropping system. Further analyses using the approach
      described in this study can be expected to provide insights into the influences
      of horticultural practices on canopy photosynthesis and the design of optimal
      crop canopies.

PMID- 24907314
TI  - Assessing the effects of architectural variations on light partitioning within
      virtual wheat-pea mixtures.
AB  - BACKGROUND AND AIMS: Predicting light partitioning in crop mixtures is a critical
      step in improving the productivity of such complex systems, and light
      interception has been shown to be closely linked to plant architecture. The aim
      of the present work was to analyse the relationships between plant architecture
      and light partitioning within wheat-pea (Triticum aestivum-Pisum sativum)
      mixtures. An existing model for wheat was utilized and a new model for pea
      morphogenesis was developed. Both models were then used to assess the effects of
      architectural variations in light partitioning. METHODS: First, a deterministic
      model (L-Pea) was developed in order to obtain dynamic reconstructions of pea
      architecture. The L-Pea model is based on L-systems formalism and consists of
      modules for 'vegetative development' and 'organ extension'. A tripartite
      simulator was then built up from pea and wheat models interfaced with a radiative
      transfer model. Architectural parameters from both plant models, selected on the
      basis of their contribution to leaf area index (LAI), height and leaf geometry,
      were then modified in order to generate contrasting architectures of wheat and
      pea. KEY RESULTS: By scaling down the analysis to the organ level, it could be
      shown that the number of branches/tillers and length of internodes significantly
      determined the partitioning of light within mixtures. Temporal relationships
      between light partitioning and the LAI and height of the different species showed
      that light capture was mainly related to the architectural traits involved in
      plant LAI during the early stages of development, and in plant height during the
      onset of interspecific competition. CONCLUSIONS: In silico experiments enabled
      the study of the intrinsic effects of architectural parameters on the
      partitioning of light in crop mixtures of wheat and pea. The findings show that
      plant architecture is an important criterion for the identification/breeding of
      plant ideotypes, particularly with respect to light partitioning.

PMID- 24907315
TI  - Extracellular enzyme activity and microbial diversity measured on seafloor
      exposed basalts from Loihi seamount indicate the importance of basalts to global
      biogeochemical cycling.
AB  - Seafloor basalts are widely distributed and host diverse prokaryotic communities,
      but no data exist concerning the metabolic rates of the resident microbial
      communities. We present here potential extracellular enzyme activities of leucine
      aminopeptidase (LAP) and alkaline phosphatase (AP) measured on basalt samples
      from different locations on Loihi Seamount, HI, coupled with analysis of
      prokaryotic biomass and pyrosequencing of the bacterial 16S rRNA gene. The
      community maximum potential enzyme activity (Vmax) of LAP ranged from 0.47 to
      0.90 nmol (g rock)(-1) h(-1); the Vmax for AP was 28 to 60 nmol (g rock)(-1) h(
      1). The Km of LAP ranged from 26 to 33 MUM, while the Km for AP was 2 to 7 MUM.
      Bacterial communities on Loihi basalts were comprised primarily of Alpha-, Delta
      , andGammaproteobacteria, Bacteroidetes, and Planctomycetes. The putative ability
      to produce LAP is evenly distributed across the most commonly detected bacterial
      orders, but the ability to produce AP is likely dominated by bacteria in the
      orders Xanthomonadales, Flavobacteriales, and Planctomycetales. The enzyme
      activities on Loihi basalts were compared to those of other marine environments
      that have been studied and were found to be similar in magnitude to those from
      continental shelf sediments and orders of magnitude higher than any measured in
      the water column, demonstrating that the potential for exposed basalts to
      transform organic matter is substantial. We propose that microbial communities on
      basaltic rock play a significant, quantifiable role in benthic biogeochemical
      processes. 

PMID- 24907317
TI  - Vertebrate decomposition is accelerated by soil microbes.
AB  - Carrion decomposition is an ecologically important natural phenomenon influenced
      by a complex set of factors, including temperature, moisture, and the activity of
      microorganisms, invertebrates, and scavengers. The role of soil microbes as
      decomposers in this process is essential but not well understood and represents a
      knowledge gap in carrion ecology. To better define the role and sources of
      microbes in carrion decomposition, lab-reared mice were decomposed on either (i)
      soil with an intact microbial community or (ii) soil that was sterilized. We
      characterized the microbial community (16S rRNA gene for bacteria and archaea,
      and the 18S rRNA gene for fungi and microbial eukaryotes) for three body sites
      along with the underlying soil (i.e., gravesoils) at time intervals coinciding
      with visible changes in carrion morphology. Our results indicate that mice placed
      on soil with intact microbial communities reach advanced stages of decomposition
      2 to 3 times faster than those placed on sterile soil. Microbial communities
      associated with skin and gravesoils of carrion in stages of active and advanced
      decay were significantly different between soil types (sterile versus untreated),
      suggesting that substrates on which carrion decompose may partially determine the
      microbial decomposer community. However, the source of the decomposer community
      (soil- versus carcass-associated microbes) was not clear in our data set,
      suggesting that greater sequencing depth needs to be employed to identify the
      origin of the decomposer communities in carrion decomposition. Overall, our data
      show that soil microbial communities have a significant impact on the rate at
      which carrion decomposes and have important implications for understanding
      carrion ecology. 

PMID- 24907316
TI  - Mechanisms of antiviral action of plant antimicrobials against murine norovirus.
AB  - Numerous plant compounds have antibacterial or antiviral properties; however,
      limited research has been conducted with nonenveloped viruses. The efficacies of
      allspice oil, lemongrass oil, and citral were evaluated against the nonenveloped
      murine norovirus (MNV), a human norovirus surrogate. The antiviral mechanisms of
      action were also examined using an RNase I protection assay, a host cell binding
      assay, and transmission electron microscopy. All three antimicrobials produced
      significant reductions (P <= 0.05) in viral infectivity within 6 h of exposure
      (0.90 log10 to 1.88 log10). After 24 h, the reductions were 2.74, 3.00, and 3.41
      log10 for lemongrass oil, citral, and allspice oil, respectively. The antiviral
      effect of allspice oil was both time and concentration dependent; the effects of
      lemongrass oil and citral were time dependent. Based on the RNase I assay,
      allspice oil appeared to act directly upon the viral capsid and RNA. The capsids
      enlarged from <= 35 nm to up to 75 nm following treatment. MNV adsorption to host
      cells was not significantly affected. Alternatively, the capsid remained intact
      following exposure to lemongrass oil and citral, which appeared to coat the
      capsid, causing nonspecific and nonproductive binding to host cells that did not
      lead to successful infection. Such contrasting effects between allspice oil and
      both lemongrass oil and citral suggest that though different plant compounds may
      yield similar reductions in virus infectivity, the mechanisms of inactivation may
      be highly varied and specific to the antimicrobial. This study demonstrates the
      antiviral properties of allspice oil, lemongrass oil, and citral against MNV and
      thus indicates their potential as natural food and surface sanitizers to control
      noroviruses.

PMID- 24907318
TI  - Revision of N2O-producing pathways in the ammonia-oxidizing bacterium
      Nitrosomonas europaea ATCC 19718.
AB  - Nitrite reductase (NirK) and nitric oxide reductase (NorB) have long been thought
      to play an essential role in nitrous oxide (N2O) production by ammonia-oxidizing
      bacteria. However, essential gaps remain in our understanding of how and when
      NirK and NorB are active and functional, putting into question their precise
      roles in N2O production by ammonia oxidizers. The growth phenotypes of the
      Nitrosomonas europaea ATCC 19718 wild-type and mutant strains deficient in
      expression of NirK, NorB, and both gene products were compared under atmospheric
      and reduced O2 tensions. Anoxic resting-cell assays and instantaneous nitrite
      (NO2 (-)) reduction experiments were done to assess the ability of the wild-type
      and mutant N. europaea strains to produce N2O through the nitrifier
      denitrification pathway. Results confirmed the role of NirK for efficient
      substrate oxidation of N. europaea and showed that NorB is involved in N2O
      production during growth at both atmospheric and reduced O2 tensions. Anoxic
      resting-cell assays and measurements of instantaneous NO2 (-) reduction using
      hydrazine as an electron donor revealed that an alternate nitrite reductase to
      NirK is present and active. These experiments also clearly demonstrated that NorB
      was the sole nitric oxide reductase for nitrifier denitrification. The results of
      this study expand the enzymology for nitrogen metabolism and N2O production by N.
      europaea and will be useful to interpret pathways in other ammonia oxidizers that
      lack NirK and/or NorB genes. 

PMID- 24907319
TI  - A novel immunofluorescence flow cytometry technique detects the expansion of
      brown tides caused by Aureoumbra lagunensis to the Caribbean Sea.
AB  - During the past 3 decades, brown tides caused by the pelagophytes Aureococcus
      anophagefferens and Aureoumbra lagunensis have caused ecological and economic
      damage to coastal ecosystems across the globe. While blooms of A. lagunensis had
      previously been confined to Texas, in 2012, an expansive brown tide occurred on
      Florida's East Coast, causing widespread disruption within the Indian River and
      Mosquito Lagoons and generating renewed interest in this organism. A major
      impediment to detailed investigations of A. lagunensis in an ecosystem setting
      has been the absence of a rapid and reliable method for cell quantification. The
      combination of their small size (3 to 5 MUm) and nondescript extracellular
      features makes identification and enumeration of these cells with conventional
      methods a challenge. Here we report the development of an immunological-based
      flow cytometry method that uses a fluorescently labeled antibody developed
      against A. lagunensis. This method is species specific, sensitive (detection
      limit of 1.5 * 10(3) cells ml(-1)), precise (1% relative standard deviation of
      replicated samples), and accurate (108% +/- 8% recovery of spiked samples) over a
      wide range of cell concentrations. Furthermore, this method effectively
      quantifies A. lagunensis in both glutaraldehyde- and formalin-preserved samples,
      yields a high throughput of samples (~35 samples h(-1)), and is cost-effective,
      making it an ideal tool for managers and scientists. This method successfully
      documented the recurrence of a brown tide bloom in Florida in 2013. Bloom
      densities were highest in June (>2.0 * 10(6) cells ml(-1)) and spanned >60 km
      from the Ponce de Leon inlet in the northern Mosquito Lagoon south to Titusville
      in the Indian River Lagoon. Low levels of A. lagunensis cells were found >250 km
      south of this region. This method also quickly and accurately identified A.
      lagunensis as the causative agent of a 2013 brown tide bloom in Guantanamo Bay,
      Cuba, and thus should prove useful for both quantifying the dynamics of ongoing
      blooms of A. lagunensis as well as documenting new outbreaks of this harmful
      alga. 

PMID- 24907320
TI  - Nonperturbative imaging of nucleoid morphology in live bacterial cells during an
      antimicrobial peptide attack.
AB  - Studies of time-dependent drug and environmental effects on single, live
      bacterial cells would benefit significantly from a permeable, nonperturbative,
      long-lived fluorescent stain specific to the nucleoids (chromosomal DNA). The
      ideal stain would not affect cell growth rate or nucleoid morphology and
      dynamics, even during laser illumination for hundreds of camera frames. In this
      study, time-dependent, single-cell fluorescence imaging with laser excitation and
      a sensitive electron-multiplying charge-coupled-device (EMCCD) camera critically
      tested the utility of "dead-cell stains" (SYTOX orange and SYTOX green) and "live
      cell stains" (DRAQ5 and SYTO 61) and also 4',6-diamidino-2-phenylindole (DAPI).
      Surprisingly, the dead-cell stains were nearly ideal for imaging live Escherichia
      coli, while the live-cell stains and DAPI caused nucleoid expansion and, in some
      cases, cell permeabilization and the halting of growth. SYTOX orange performed
      well for both the Gram-negative E. coli and the Gram-positive Bacillus subtilis.
      In an initial application, we used two-color fluorescence imaging to show that
      the antimicrobial peptide cecropin A destroyed nucleoid-ribosome segregation over
      20 min after permeabilization of the E. coli cytoplasmic membrane, reminiscent of
      the long-term effects of the drug rifampin. In contrast, the human cathelicidin
      LL-37, while similar to cecropin A in structure, length, charge, and the ability
      to permeabilize bacterial membranes, had no observable effect on nucleoid
      ribosome segregation. Possible underlying causes are suggested. 

PMID- 24907321
TI  - Use of silica-encapsulated Pseudomonas sp. strain NCIB 9816-4 in biodegradation
      of novel hydrocarbon ring structures found in hydraulic fracturing waters.
AB  - The most problematic hydrocarbons in hydraulic fracturing (fracking) wastewaters
      consist of fused, isolated, bridged, and spiro ring systems, and ring systems
      have been poorly studied with respect to biodegradation, prompting the testing
      here of six major ring structural subclasses using a well-characterized bacterium
      and a silica encapsulation system previously shown to enhance biodegradation. The
      direct biological oxygenation of spiro ring compounds was demonstrated here.
      These and other hydrocarbon ring compounds have previously been shown to be
      present in flow-back waters and waters produced from hydraulic fracturing
      operations. Pseudomonas sp. strain NCIB 9816-4, containing naphthalene
      dioxygenase, was selected for its broad substrate specificity, and it was
      demonstrated here to oxidize fundamental ring structures that are common in shale
      derived waters but not previously investigated with this or related enzymes.
      Pseudomonas sp. NCIB 9816-4 was tested here in the presence of a silica
      encasement, a protocol that has previously been shown to protect bacteria against
      the extremes of salinity present in fracking wastewaters. These studies
      demonstrate the degradation of highly hydrophobic compounds by a silica
      encapsulated model bacterium, demonstrate what it may not degrade, and contribute
      to knowledge of the full range of hydrocarbon ring compounds that can be oxidized
      using Pseudomonas sp. NCIB 9816-4. 

PMID- 24907322
TI  - Lactulose and Lactobacillus plantarum, a potential complementary synbiotic to
      control postweaning colibacillosis in piglets.
AB  - The potential of a prebiotic oligosaccharide lactulose, a probiotic strain of
      Lactobacillus plantarum, or their synbiotic combination to control postweaning
      colibacillosis in pigs was evaluated using an enterotoxigenic Escherichia coli
      (ETEC) K88 oral challenge. Seventy-two weanlings were fed four diets: a control
      diet (CTR), that diet supplemented with L. plantarum (2 * 10(10) CFU . day(-1))
      (LPN), that diet supplemented with 10 g . kg(-1) lactulose (LAC), or a
      combination of the two treatments (SYN). After 7 days, the pigs were orally
      challenged. Six pigs per treatment were euthanized on days 6 and 10 postchallenge
      (PC). Inclusion of lactulose improved the average daily gain (ADG) (P < 0.05) and
      increased lactobacilli (P < 0.05) and the percentage of butyric acid (P < 0.02)
      in the colon. An increase in the ileum villous height (P < 0.05) and a reduction
      of the pig major acute-phase protein (Pig-MAP) in serum (P < 0.01) were observed
      also. The inclusion of the probiotic increased numbers of L. plantarum bacteria
      in the ileum and colon (P < 0.05) and in the total lactobacilli in the colon and
      showed a trend to reduce diarrhea (P = 0.09). The concentrations of ammonia in
      ileal and colonic digesta were decreased (P < 0.05), and the villous height (P <
      0.01) and number of ileal goblet cells (P < 0.05) increased, at day 10 PC. A
      decrease in plasmatic tumor necrosis factor alpha (TNF-alpha) (P < 0.01) was also
      seen. The positive effects of the two additives were combined in the SYN
      treatment, resulting in a complementary synbiotic with potential to be used to
      control postweaning colibacillosis. 

PMID- 24907323
TI  - Knockout of extracytoplasmic function sigma factor ECF-10 affects stress
      resistance and biofilm formation in Pseudomonas putida KT2440.
AB  - Pseudomonas putida is a Gram-negative soil bacterium which is well-known for its
      versatile lifestyle, controlled by a large repertoire of transcriptional
      regulators. Besides one- and two-component regulatory systems, the genome of P.
      putida reveals 19 extracytoplasmic function (ECF) sigma factors involved in the
      adaptation to changing environmental conditions. In this study, we demonstrate
      that knockout of extracytoplasmic function sigma factor ECF-10, encoded by open
      reading frame PP4553, resulted in 2- to 4-fold increased antibiotic resistance to
      quinolone, beta-lactam, sulfonamide, and chloramphenicol antibiotics. In
      addition, the ECF-10 mutant exhibited enhanced formation of biofilms after 24 h
      of incubation. Transcriptome analysis using Illumina sequencing technology
      resulted in the detection of 12 genes differentially expressed (>2-fold) in the
      ECF-10 knockout mutant strain compared to their levels of expression in wild-type
      cells. Among the upregulated genes were ttgA, ttgB, and ttgC, which code for the
      major multidrug efflux pump TtgABC in P. putida KT2440. Investigation of an ECF
      10 and ttgA double-knockout strain and a ttgABC-overexpressing strain
      demonstrated the involvement of efflux pump TtgABC in the stress resistance and
      biofilm formation phenotypes of the ECF-10 mutant strain, indicating a new role
      for this efflux pump beyond simple antibiotic resistance in P. putida KT2440. 

PMID- 24907324
TI  - A third subunit in ancestral cytochrome c-dependent nitric oxide reductases.
AB  - Reduction of NO to N2O by denitrifiying bacteria is catalyzed either by a
      monomeric quinol-nitric oxide reductase (qNor) or by a heterodimeric cytochrome c
      dependent nitric oxide reductase (cNor). In ancient thermophilic bacteria
      belonging to the Thermales and Aquificales phylogenetic groups, the cluster
      encoding the cNor includes a small third gene (norH), in addition to those
      encoding homologues to the subunits of a typical cNor (norC and norB). We show in
      Thermus thermophilus that the three genes are cotranscribed in a single mRNA from
      an inducible promoter. The isolation of individual nor mutants and the production
      in vivo of His-tagged NorH protein followed by immobilized-metal affinity
      chromatography (IMAC) allowed us to conclude that NorH constitutes a third
      subunit of the cNor from T. thermophilus, which is involved in denitrification in
      vivo, likely allowing more efficient electron transport to cNor. 

PMID- 24907325
TI  - Carriage of Staphylococcus aureus by free-living wild animals in Spain.
AB  - The presence of methicillin-susceptible Staphylococcus aureus (MSSA) was analyzed
      in different free-living wild animals to assess the genetic diversity and
      predominant genotypes on each animal species. Samples were taken from the skin
      and/or nares, and isolates were characterized by spa typing, multilocus sequence
      typing (MLST) and antimicrobial susceptibility testing. The proportion of MSSA
      carriers were 5.00, 22.93, 19.78, and 17.67% in Eurasian griffon vulture, Iberian
      ibex, red deer, and wild boar, respectively (P = 0.057). A higher proportion of
      isolates (P = 0.000) were recovered from nasal samples (78.51%) than skin samples
      (21.49%), but the 9.26% of red deer and 18.25% of wild boar would have been
      undetected if only nasal samples had been tested. Sixty-three different spa types
      were identified, including 25 new spa types. The most common were t528 (43.59%)
      in Iberian ibex, t548 and t11212 (15.79% and 14.04%) in red deer, and t3750
      (36.11%) in wild boar. By MLST, 27 STs were detected, of which 12 had not been
      described previously. The most frequent were ST581 for Iberian ibex (48.72%),
      ST425 for red deer (29.82%), and ST2328 for wild boar (42.36%). Isolates from
      Eurasian griffon vulture belong to ST133. Host specificity has been observed for
      the most frequent spa types and STs (P = 0.000). The highest resistance
      percentage was found against benzylpenicillin (average, 22.2%), although most of
      the S. aureus isolates were susceptible to all antimicrobial tested. Basically,
      MSSA isolates were different from those MRSA isolates previously detected in the
      same animal species. 

PMID- 24907326
TI  - To be or not to be a poly(3-hydroxybutyrate) (PHB) depolymerase: PhaZd1 (PhaZ6)
      and PhaZd2 (PhaZ7) of Ralstonia eutropha, highly active PHB depolymerases with no
      detectable role in mobilization of accumulated PHB.
AB  - The putative physiological functions of two related intracellular poly(3
      hydroxybutyrate) (PHB) depolymerases, PhaZd1 and PhaZd2, of Ralstonia eutropha
      H16 were investigated. Purified PhaZd1 and PhaZd2 were active with native PHB
      granules in vitro. Partial removal of the proteinaceous surface layer of native
      PHB granules by trypsin treatment or the use of PHB granules isolated from
      DeltaphaP1 or DeltaphaP1-phaP5 mutant strains resulted in increased specific PHB
      depolymerase activity, especially for PhaZd2. Constitutive expression of PhaZd1
      or PhaZd2 reduced or even prevented the accumulation of PHB under PHB-permissive
      conditions in vivo. Expression of translational fusions of enhanced yellow
      fluorescent protein (EYFP) with PhaZd1 and PhaZd2 in which the active-site
      serines (S190 and Ser193) were replaced with alanine resulted in the
      colocalization of only PhaZd1 fusions with PHB granules. C-terminal fusions of
      inactive PhaZd2(S193A) with EYFP revealed the presence of spindle-like
      structures, and no colocalization with PHB granules was observed. Chromosomal
      deletion of phaZd1, phaZd2, or both depolymerase genes had no significant effect
      on PHB accumulation and mobilization during growth in nutrient broth (NB) or NB
      gluconate medium. Moreover, neither proteome analysis of purified native PHB
      granules nor lacZ fusion studies gave any indication that PhaZd1 or PhaZd2 was
      detectably present in the PHB granule fraction or expressed at all during growth
      on NB-gluconate medium. In conclusion, PhaZd1 and PhaZd2 are two PHB
      depolymerases with a high capacity to degrade PHB when artificially expressed but
      are apparently not involved in PHB mobilization in the wild type. The true in
      vivo functions of PhaZd1 and PhaZd2 remain obscure. 

PMID- 24907327
TI  - Genomic heterogeneity and ecological speciation within one subspecies of Bacillus
      subtilis.
AB  - Closely related bacterial genomes usually differ in gene content, suggesting that
      nearly every strain in nature may be ecologically unique. We have tested this
      hypothesis by sequencing the genomes of extremely close relatives within a
      recognized taxon and analyzing the genomes for evidence of ecological
      distinctness. We compared the genomes of four Death Valley isolates plus the
      laboratory strain W23, all previously classified as Bacillus subtilis subsp.
      spizizenii and hypothesized through multilocus analysis to be members of the same
      ecotype (an ecologically homogeneous population), named putative ecotype 15
      (PE15). These strains showed a history of positive selection on amino acid
      sequences in 38 genes. Each of the strains was under a different regimen of
      positive selection, suggesting that each strain is ecologically unique and
      represents a distinct ecological speciation event. The rate of speciation appears
      to be much faster than can be resolved with multilocus sequencing. Each PE15
      strain contained unique genes known to confer a function for bacteria.
      Remarkably, no unique gene conferred a metabolic system or subsystem function
      that was not already present in all the PE15 strains sampled. Thus, the origin of
      ecotypes within this clade shows no evidence of qualitative divergence in the set
      of resources utilized. Ecotype formation within this clade is consistent with the
      nanoniche model of bacterial speciation, in which ecotypes use the same set of
      resources but in different proportions, and genetic cohesion extends beyond a
      single ecotype to the set of ecotypes utilizing the same resources. 

PMID- 24907328
TI  - Elucidation of insertion elements carried on plasmids and in vitro construction
      of shuttle vectors from the toxic cyanobacterium Planktothrix.
AB  - Several gene clusters that are responsible for toxin synthesis in bloom-forming
      cyanobacteria have been found to be associated with transposable elements (TEs).
      In particular, insertion sequence (IS) elements were shown to play a role in the
      inactivation or recombination of the genes responsible for cyanotoxin synthesis.
      Plasmids have been considered important vectors of IS element distribution to the
      host. In this study, we aimed to elucidate the IS elements propagated on the
      plasmids and the chromosome of the toxic cyanobacterium Planktothrix agardhii
      NIVA-CYA126/8 by means of high-throughput sequencing. In total, five plasmids
      (pPA5.5, pPA14, pPA50, pPA79, and pPA115, of 5, 6, 50, 79, and 120 kbp,
      respectively) were elucidated, and two plasmids (pPA5.5, pPA115) were found to
      propagate full IS element copies. Large stretches of shared DNA information
      between plasmids were constituted of TEs. Two plasmids (pPA5.5, pPA14) were used
      as candidates to engineer shuttle vectors (named pPA5.5SV and pPA14SV,
      respectively) in vitro by PCR amplification and the subsequent transposition of
      the Tn5 cat transposon containing the R6Kgamma origin of replication of
      Escherichia coli. While pPA5.5SV was found to be fully segregated, pPA14SV
      consistently co-occurred with its wild-type plasmid even under the highest
      selective pressure. Interestingly, the Tn5 cat transposon became transferred by
      homologous recombination into another plasmid, pPA50. The availability of shuttle
      vectors is considered to be of relevance in investigating genome plasticity as a
      consequence of homologous recombination events. Combining the potential of high
      throughput sequencing and in vitro production of shuttle vectors makes it simple
      to produce species-specific shuttle vectors for many cultivable prokaryotes. 

PMID- 24907329
TI  - Antifouling coatings influence both abundance and community structure of
      colonizing biofilms: a case study in the Northwestern Mediterranean Sea.
AB  - When immersed in seawater, substrates are rapidly colonized by both micro- and
      macroorganisms. This process is responsible for important economic and ecological
      prejudices, particularly when related to ship hulls or aquaculture nets.
      Commercial antifouling coatings are supposed to reduce biofouling, i.e., micro-
      and macrofoulers. In this study, biofilms that primarily settled on seven
      different coatings (polyvinyl chloride [PVC], a fouling release coating [FRC],
      and five self-polishing copolymer coatings [SPC], including four commercial ones)
      were quantitatively studied, after 1 month of immersion in summer in the Toulon
      Bay (Northwestern Mediterranean Sea, France), by using flow cytometry (FCM),
      microscopy, and denaturing gradient gel electrophoresis. FCM was used after a
      pretreatment to separate cells from the biofilm matrix, in order to determine
      densities of heterotrophic bacteria, picocyanobacteria, and pico- and
      nanoeukaryotes on these coatings. Among diatoms, the only microphytobenthic class
      identified by microscopy, Licmophora, Navicula, and Nitzschia were determined to
      be the dominant taxa. Overall, biocide-free coatings showed higher densities than
      all other coatings, except for one biocidal coating, whatever the group of
      microorganisms. Heterotrophic bacteria always showed the highest densities, and
      diatoms showed the lowest, but the relative abundances of these groups varied
      depending on the coating. In particular, the copper-free SPC failed to prevent
      diatom settlement, whereas the pyrithione-free SPC exhibited high
      picocyanobacterial density. These results highlight the interest in FCM for
      antifouling coating assessment as well as specific selection among microbial
      communities by antifouling coatings. 

PMID- 24907330
TI  - Thermal and nonthermal effects of discontinuous microwave exposure (2.45
      gigahertz) on the cell membrane of Escherichia coli.
AB  - The aim of this study was to investigate the effects on the cell membranes of
      Escherichia coli of 2.45-GHz microwave (MW) treatment under various conditions
      with an average temperature of the cell suspension maintained at 37 degrees C in
      order to examine the possible thermal versus nonthermal effects of short-duration
      MW exposure. To this purpose, microwave irradiation of bacteria was performed
      under carefully defined and controlled parameters, resulting in a discontinuous
      MW exposure in order to maintain the average temperature of the bacterial cell
      suspensions at 37 degrees C. Escherichia coli cells were exposed to 200- to 2,000
      W discontinuous microwave (DW) treatments for different periods of time. For each
      experiment, conventional heating (CH) in a water bath at 37 degrees C was
      performed as a control. The effects of DW exposure on cell membranes was
      investigated using flow cytometry (FCM), after propidium iodide (PI) staining of
      cells, in addition to the assessment of intracellular protein release in
      bacterial suspensions. No effect was detected when bacteria were exposed to
      conventional heating or 200 W, whereas cell membrane integrity was slightly
      altered when cell suspensions were subjected to powers ranging from 400 to 2,000
      W. Thermal characterization suggested that the temperature reached by the
      microwave-exposed samples for the contact time studied was not high enough to
      explain the measured modifications of cell membrane integrity. Because the
      results indicated that the cell response is power dependent, the hypothesis of a
      specific electromagnetic threshold effect, probably related to the temperature
      increase, can be advanced. 

PMID- 24907331
TI  - epsilon-Poly-L-lysine peptide chain length regulated by the linkers connecting
      the transmembrane domains of epsilon-Poly-L-lysine synthetase.
AB  - epsilon-Poly-l-lysine (epsilon-PL), consisting of 25 to 35 l-lysine residues with
      linkages between the alpha-carboxyl groups and epsilon-amino groups, is produced
      by Streptomyces albulus NBRC14147. epsilon-PL synthetase (Pls) is a membrane
      protein with six transmembrane domains (TM1 to TM6) as well as both an
      adenylation domain and a thiolation domain, characteristic of the nonribosomal
      peptide synthetases. Pls directly generates epsilon-PL chain length diversity (25
      to 35-mer), but the processes that control the chain length of epsilon-PL during
      the polymerization reaction are still not fully understood. Here, we report on
      the identification of Pls amino acid residues involved in the regulation of the
      epsilon-PL chain length. From approximately 12,000 variants generated by random
      mutagenesis, we found 8 Pls variants that produced shorter chains of epsilon-PL.
      These variants have one or more mutations in two linker regions connecting the
      TM1 and TM2 domains and the TM3 and TM4 domains. In the Pls catalytic mechanism,
      the growing chain of epsilon-PL is not tethered to the enzyme, implying that the
      enzyme must hold the growing chain until the polymerization reaction is complete.
      Our findings reveal that the linker regions are important contributors to grasp
      the growing chain of epsilon-PL. 

PMID- 24907332
TI  - Identification and characterization of a halotolerant, cold-active marine endo
      beta-1,4-glucanase by using functional metagenomics of seaweed-associated
      microbiota.
AB  - A metagenomic library was constructed from microorganisms associated with the
      brown alga Ascophyllum nodosum. Functional screening of this library revealed 13
      novel putative esterase loci and two glycoside hydrolase loci. Sequence and gene
      cluster analysis showed the wide diversity of the identified enzymes and gave an
      idea of the microbial populations present during the sample collection period.
      Lastly, an endo-beta-1,4-glucanase having less than 50% identity to sequences of
      known cellulases was purified and partially characterized, showing activity at
      low temperature and after prolonged incubation in concentrated salt solutions. 

PMID- 24907333
TI  - Rubber oxygenase and latex clearing protein cleave rubber to different products
      and use different cleavage mechanisms.
AB  - Two types of enzyme for oxidative cleavage of poly(cis-1,4-isoprene) are known.
      One is rubber oxygenase (RoxA) that is secreted by Xanthomonas sp. strain 35Y and
      a few other Gram-negative rubber-degrading bacteria during growth on
      polyisoprene. RoxA was studied in the past, and the recently solved structure
      showed a structural relationship to bacterial cytochrome c peroxidases (J. Seidel
      et al., Proc. Natl. Acad. Sci. U. S. A. 110:13833-13838, 2013,
      http://dx.doi.org/10.1073/pnas.1305560110). The other enzyme is latex-clearing
      protein (Lcp) that is secreted by rubber-degrading actinomycetes, but Lcp has not
      yet been purified. Here, we expressed Lcp of Streptomyces sp. strain K30 in a
      DeltaroxA background of Xanthomonas sp. strain 35Y and purified native (untagged)
      Lcp. The specific activities of Lcp and RoxA were 0.70 and 0.48 U/mg,
      respectively. Lcp differed from RoxA in the absence of heme groups and other
      characteristics. Notably, Lcp degraded polyisoprene via endo-type cleavage to
      tetra-C20 and higher oligo-isoprenoids with aldehyde and keto end groups, whereas
      RoxA used an exo-type cleavage mechanism to give the main end product 12-oxo-4,8
      dimethyltrideca-4,8-diene-1-al (ODTD). RoxA was able to cleave isolated Lcp
      derived oligo-isoprenoid molecules to ODTD. Inhibitor studies, spectroscopic
      investigations and metal analysis gave no indication for the presence of iron,
      other metals, or cofactors in Lcp. Our results suggest that Lcp could be a member
      of the growing group of cofactor-independent oxygenases and differs in the
      cleavage mechanism from heme-dependent RoxA. In conclusion, RoxA and Lcp
      represent two different answers to the same biochemical problem, the cleavage of
      polyisoprene, a polymer that has carbon-carbon double bonds as the only
      functional groups for enzymatic attack. 

PMID- 24907334
TI  - Distribution of virulence-associated genes and genetic relationships in non
      O1/O139 Vibrio cholerae aquatic isolates from China.
AB  - Non-O1/O139 Vibrio cholerae is naturally present in aquatic ecosystems and has
      been linked with cholera-like diarrhea and local outbreaks. The distribution of
      virulence-associated genes and genetic relationships among aquatic isolates from
      China are largely unknown. In this study, 295 aquatic isolates of V. cholerae non
      O1/O139 serogroups from different regions in China were investigated. Only one
      isolate was positive for ctxB and harbored a rare genotype; 10 (3.4%) isolates
      carried several types of rstR sequences, eight of which carried rare types of
      toxin-coregulated pili (tcpA). Furthermore, 16 (5.4%) isolates carried incomplete
      (with partial open reading frames [ORFs]) vibrio seventh pandemic island I (VSP
      I) or VSP-II clusters, which were further classified as 11 novel types. PCR-based
      analyses revealed remarkable variations in the distribution of putative virulence
      genes, including mshA (95.6%), hlyA (95.3%), rtxC (89.8%), rtxA (82.7%), IS1004
      (52.9%), chxA (30.2%), SXT (15.3%), type III secretion system (18.0%), and NAG-ST
      (3.7%) genes. There was no correlation between the prevalence of putative
      virulence genes and that of CTX prophage or TCP genes, whereas there were
      correlations among the putative virulence genes. Further multilocus sequence
      typing (MLST) placed selected isolates (n = 70) into 69 unique sequence types
      (STs), which were different from those of the toxigenic O1 and O139 counterparts,
      and each isolate occupied a different position in the MLST tree. The V. cholerae
      non-O1/O139 aquatic isolates predominant in China have high genotypic diversity;
      these strains constitute a reservoir of potential virulence genes, which may
      contribute to evolution of pathogenic isolates. 

PMID- 24907335
TI  - Biosynthesis of the beta-methylarginine residue of peptidyl nucleoside
      arginomycin in Streptomyces arginensis NRRL 15941.
AB  - The peptidyl nucleoside arginomycin is active against Gram-positive bacteria and
      fungi but displays much lower toxicity to mice than its analog blasticidin S. It
      features a rare amino acid, beta-methylarginine, which is attached to the
      deoxyhexose moiety via a 4'-aminoacyl bond. We here report cloning of the
      complete biosynthetic gene cluster for arginomycin from Streptomyces arginensis
      NRRL 15941. Among the 14 putative essential open reading frames, argM, encoding
      an aspartate aminotransferase (AAT), and adjacent argN, encoding an S-adenosyl
      methionine (SAM)-dependent methyltransferase, are coupled to catalyze arginine
      and yield beta-methylarginine in Escherichia coli. Purified ArgM can transfer the
      alpha-amino group of l-arginine to alpha-ketoglutaric acid to give glutamate and
      thereby converts l-arginine to 5-guanidino-2-oxopentanoic acid, which is
      methylated at the C-3 position by ArgN to form 5-guanidino-3-methyl-2
      oxopentanoic acid. Iteratively, ArgM specifically catalyzes transamination from
      the donor l-aspartate to the resulting 5-guanidino-3-methyl-2-oxopentanoic acid,
      generating beta-methylarginine. The complete and concise biosynthetic pathway for
      the rare and bioactive amino acid revealed by this study may pave the way for the
      production of beta-methylarginine either by enzymatic conversion or by engineered
      living cells. 

PMID- 24907336
TI  - Effect of the surfactant tween 80 on the detachment and dispersal of Salmonella
      enterica serovar Thompson single cells and aggregates from cilantro leaves as
      revealed by image analysis.
AB  - Salmonella enterica has the ability to form biofilms and large aggregates on
      produce surfaces, including on cilantro leaves. Aggregates of S. enterica serovar
      Thompson that remained attached to cilantro leaves after rigorous washing and
      that were present free or bound to dislodged leaf tissue in the wash suspension
      were observed by confocal microscopy. Measurement of S. Thompson population sizes
      in the leaf washes by plate counts failed to show an effect of 0.05% Tween 80 on
      the removal of the pathogen from cilantro leaves 2 and 6 days after inoculation.
      On the contrary, digital image analysis of micrographs of single cells and
      aggregates of green fluorescent protein (GFP)-S. Thompson present in cilantro
      leaf washes revealed that single cells represented 13.7% of the cell assemblages
      in leaf washes containing Tween 80, versus 9.3% in those without the surfactant.
      Moreover, Tween 80 decreased the percentage of the total S. Thompson cell
      population located in aggregates equal to or larger than 64 cells from 9.8% to
      4.4% (P < 0.05). Regression analysis of the frequency distribution of aggregate
      size in leaf washes with and without Tween 80 showed that the surfactant promoted
      the dispersal of cells from large aggregates into smaller ones and into single
      cells (P < 0.05). Our study underlines the importance of investigating bacterial
      behavior at the scale of single cells in order to uncover trends undetectable at
      the population level by bacterial plate counts. Such an approach may provide
      valuable information to devise strategies aimed at enhancing the efficacy of
      produce sanitization treatments. 

PMID- 24907337
TI  - Profile of secreted hydrolases, associated proteins, and SlpA in
      Thermoanaerobacterium saccharolyticum during the degradation of hemicellulose.
AB  - Thermoanaerobacterium saccharolyticum, a Gram-positive thermophilic anaerobic
      bacterium, grows robustly on insoluble hemicellulose, which requires a
      specialized suite of secreted and transmembrane proteins. We report here the
      characterization of proteins secreted by this organism. Cultures were grown on
      hemicellulose, glucose, xylose, starch, and xylan in pH-controlled bioreactors,
      and samples were analyzed via spotted microarrays and liquid chromatography-mass
      spectrometry. Key hydrolases and transporters employed by T. saccharolyticum for
      growth on hemicellulose were, for the most part, hitherto uncharacterized and
      existed in two clusters (Tsac_1445 through Tsac_1464 for xylan/xylose and
      Tsac_1344 through Tsac_1349 for starch). A phosphotransferase system subunit,
      Tsac_0032, also appeared to be exclusive to growth on glucose. Previously
      identified hydrolases that showed strong conditional expression changes included
      XynA (Tsac_1459), XynC (Tsac_0897), and a pullulanase, Apu (Tsac_1342). An
      omnipresent transcript and protein making up a large percentage of the overall
      secretome, Tsac_0361, was tentatively identified as the primary S-layer component
      in T. saccharolyticum, and deletion of the Tsac_0361 gene resulted in gross
      morphological changes to the cells. The view of hemicellulose degradation
      revealed here will be enabling for metabolic engineering efforts in biofuel
      producing organisms that degrade cellulose well but lack the ability to
      catabolize C5 sugars. 

PMID- 24907338
TI  - Discovery of gene cluster for mycosporine-like amino acid biosynthesis from
      Actinomycetales microorganisms and production of a novel mycosporine-like amino
      acid by heterologous expression.
AB  - Mycosporines and mycosporine-like amino acids (MAAs), including shinorine
      (mycosporine-glycine-serine) and porphyra-334 (mycosporine-glycine-threonine),
      are UV-absorbing compounds produced by cyanobacteria, fungi, and marine micro-
      and macroalgae. These MAAs have the ability to protect these organisms from
      damage by environmental UV radiation. Although no reports have described the
      production of MAAs and the corresponding genes involved in MAA biosynthesis from
      Gram-positive bacteria to date, genome mining of the Gram-positive bacterial
      database revealed that two microorganisms belonging to the order Actinomycetales,
      Actinosynnema mirum DSM 43827 and Pseudonocardia sp. strain P1, possess a gene
      cluster homologous to the biosynthetic gene clusters identified from
      cyanobacteria. When the two strains were grown in liquid culture, Pseudonocardia
      sp. accumulated a very small amount of MAA-like compound in a medium-dependent
      manner, whereas A. mirum did not produce MAAs under any culture conditions,
      indicating that the biosynthetic gene cluster of A. mirum was in a cryptic state
      in this microorganism. In order to characterize these biosynthetic gene clusters,
      each biosynthetic gene cluster was heterologously expressed in an engineered
      host, Streptomyces avermitilis SUKA22. Since the resultant transformants carrying
      the entire biosynthetic gene cluster controlled by an alternative promoter
      produced mainly shinorine, this is the first confirmation of a biosynthetic gene
      cluster for MAA from Gram-positive bacteria. Furthermore, S. avermitilis SUKA22
      transformants carrying the biosynthetic gene cluster for MAA of A. mirum
      accumulated not only shinorine and porphyra-334 but also a novel MAA. Structure
      elucidation revealed that the novel MAA is mycosporine-glycine-alanine, which
      substitutes l-alanine for the l-serine of shinorine. 

PMID- 24907339
TI  - Applied usage of yeast spores as chitosan beads.
AB  - In this study, we present a nonhazardous biological method of producing chitosan
      beads using the budding yeast Saccharomyces cerevisiae. Yeast cells cultured
      under conditions of nutritional starvation cease vegetative growth and instead
      form spores. The spore wall has a multilaminar structure with the chitosan layer
      as the second outermost layer. Thus, removal of the outermost dityrosine layer by
      disruption of the DIT1 gene, which is required for dityrosine synthesis, leads to
      exposure of the chitosan layer at the spore surface. In this way, spores can be
      made to resemble chitosan beads. Chitosan has adsorptive features and can be used
      to remove heavy metals and negatively charged molecules from solution. Consistent
      with this practical application, we find that spores are capable of adsorbing
      heavy metals such as Cu(2+), Cr(3+), and Cd(2+), and removal of the dityrosine
      layer further improves the adsorption. Removal of the chitosan layer decreases
      the adsorption, indicating that chitosan works as an adsorbent in the spores.
      Besides heavy metals, spores can also adsorb a negatively charged cholesterol
      derivative, taurocholic acid. Furthermore, chitosan is amenable to chemical
      modifications, and, consistent with this property, dit1Delta spores can serve as
      a carrier for immobilization of enzymes. Given that yeast spores are a natural
      product, our results demonstrate that they, and especially dit1Delta mutants, can
      be used as chitosan beads and used for multiple purposes. 

PMID- 24907340
TI  - Dosimetric and geometric evaluation of the use of deformable image registration
      in adaptive intensity-modulated radiotherapy for head-and-neck cancer.
AB  - The aim of this study was to carry out geometric and dosimetric evaluation of the
      usefulness of a deformable image registration algorithm utilized for adaptive
      head-and-neck intensity-modulated radiotherapy. Data consisted of seven patients,
      each with a planning CT (pCT), a rescanning CT (ReCT) and a cone beam CT (CBCT).
      The CBCT was acquired on the same day (+/- 1 d) as the ReCT (i.e. at Fraction 17,
      18, 23, 24 or 29). The ReCT served as ground truth. A deformed CT (dCT) with
      structures was created by deforming the pCT to the CBCT. The geometrical
      comparison was based on the volumes of the deformed, and the manually delineated
      structures on the ReCT. Likewise, the center of mass shift (CMS) and the Dice
      similarity coefficient were determined. The dosimetric comparison was performed
      by recalculating the initial treatment plan on the dCT and the ReCT. Dose-volume
      histogram (DVH) points and a range of conformity measures were used for the
      evaluation. We found a significant difference in the median volume of the dCT
      relative to that of the ReCT. Median CMS values were ~ 2-5 mm, except for the
      spinal cord, where the median CMS was 8 mm. Dosimetric evaluation of target
      structures revealed small differences, while larger differences were observed for
      organs at risk. The deformed structures cannot fully replace manually delineated
      structures. Based on both geometrical and dosimetrical measures, there is a
      tendency for the dCT to overestimate the need for replanning, compared with the
      ReCT.

PMID- 24907341
TI  - The Receptor-Like Kinase SIT1 Mediates Salt Sensitivity by Activating MAPK3/6 and
      Regulating Ethylene Homeostasis in Rice.
AB  - High salinity causes growth inhibition and shoot bleaching in plants that do not
      tolerate high salt (glycophytes), including most crops. The molecules affected
      directly by salt and linking the extracellular stimulus to intracellular
      responses remain largely unknown. Here, we demonstrate that rice (Oryza sativa)
      Salt Intolerance 1 (SIT1), a lectin receptor-like kinase expressed mainly in root
      epidermal cells, mediates salt sensitivity. NaCl rapidly activates SIT1, and in
      the presence of salt, as SIT1 kinase activity increased, plant survival
      decreased. Rice MPK3 and MPK6 function as the downstream effectors of SIT1. SIT1
      phosphorylates MPK3 and 6, and their activation by salt requires SIT1. SIT1
      mediates ethylene production and salt-induced ethylene signaling. SIT1 promotes
      accumulation of reactive oxygen species (ROS), leading to growth inhibition and
      plant death under salt stress, which occurred in an MPK3/6- and ethylene
      signaling-dependent manner in Arabidopsis thaliana. Our findings demonstrate the
      existence of a SIT1-MPK3/6 cascade that mediates salt sensitivity by affecting
      ROS and ethylene homeostasis and signaling. These results provide important
      information for engineering salt-tolerant crops.

PMID- 24907342
TI  - An Uncharacterized Apocarotenoid-Derived Signal Generated in zeta-Carotene
      Desaturase Mutants Regulates Leaf Development and the Expression of Chloroplast
      and Nuclear Genes in Arabidopsis.
AB  - In addition to acting as photoprotective compounds, carotenoids also serve as
      precursors in the biosynthesis of several phytohormones and proposed regulatory
      signals. Here, we report a signaling process derived from carotenoids that
      regulates early chloroplast and leaf development. Biosynthesis of the signal
      depends on zeta-carotene desaturase activity encoded by the zeta-CAROTENE
      DESATURASE (ZDS)/CHLOROPLAST BIOGENESIS5 (CLB5) gene in Arabidopsis thaliana.
      Unlike other carotenoid-deficient plants, zds/clb5 mutant alleles display
      profound alterations in leaf morphology and cellular differentiation as well as
      altered expression of many plastid- and nucleus-encoded genes. The leaf
      developmental phenotypes and gene expression alterations of zds/clb5/spc1/pde181
      plants are rescued by inhibitors or mutations of phytoene desaturase,
      demonstrating that phytofluene and/or zeta-carotene are substrates for an
      unidentified signaling molecule. Our work further demonstrates that this signal
      is an apocarotenoid whose synthesis requires the activity of the carotenoid
      cleavage dioxygenase CCD4.

PMID- 24907343
TI  - Themis2 is not required for B cell development, activation, and antibody
      responses.
AB  - Themis1 is a protein implicated in transducing signals from the TCR. Mice
      deficient in Themis1 show a strong impairment in T cell selection in the thymus
      and defective T cell activation. The related Themis2 protein is expressed in B
      cells where it associates with signaling proteins Grb2 and Vav1, and is tyrosine
      phosphorylated after BCR stimulation. Thus, it has been proposed that Themis2 may
      transduce BCR signals, and hence play important roles in B cell development and
      activation. In this article, we show that Themis2 is expressed in all developing
      subsets of B cells, in mature follicular and marginal zone B cells, and in
      activated B cells, including germinal center B cells and plasma cells. In
      contrast, B lineage cells express no other Themis-family genes. Activation of B
      cells leads to reduced Themis2 expression, although it remains the only Themis
      family protein expressed. To analyze the physiological function of Themis2, we
      generated a Themis2-deficient mouse strain. Surprisingly, we found that Themis2
      is not required for B cell development, for activation, or for Ab responses
      either to model Ags or to influenza viral infection. 

PMID- 24907344
TI  - Mycobacterium tuberculosis keto-mycolic acid and macrophage nuclear receptor TR4
      modulate foamy biogenesis in granulomas: a case of a heterologous and
      noncanonical ligand-receptor pair.
AB  - The cell wall of Mycobacterium tuberculosis is configured of bioactive lipid
      classes that are essential for virulence and potentially involved in the
      formation of foamy macrophages (FMs) and granulomas. Our recent work established
      crosstalk between M. tuberculosis cell wall lipids and the host lipid-sensing
      nuclear receptor TR4. In this study, we have characterized, identified, and
      adopted a heterologous ligand keto-mycolic acid from among M. tuberculosis lipid
      repertoire for the host orphan NR TR4. Crosstalk between cell wall lipids and TR4
      was analyzed by transactivation and promoter reporter assays. Mycolic acid (MA)
      was found to transactivate TR4 significantly compared with other cell wall
      lipids. Among the MA, the oxygenated form, keto-MA, was responsible for
      transactivation, and the identity was validated by TR4 binding assays followed by
      TLC and nuclear magnetic resonance. Isothermal titration calorimetry revealed
      that keto-MA binding to TR4 is energetically favorable. This keto-MA-TR4 axis
      seems to be essential to this oxygenated MA induction of FMs and granuloma
      formation as evaluated by in vitro and in vivo model of granuloma formation. TR4
      binding with keto-MA features a unique association of host nuclear receptor with
      a bacterial lipid and adds to the presently known ligand repertoire beyond
      dietary lipids. Pharmacologic modulation of this heterologous axis may hold
      promise as an adjunct therapy to frontline tuberculosis drugs. 

PMID- 24907345
TI  - The inhibitory effect of IFN-gamma on protease HTRA1 expression in rheumatoid
      arthritis.
AB  - The high temperature requirement A1 (HTRA1) is a potent protease involved in many
      diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms
      that control HTRA1 expression need to be determined. In this study, we
      demonstrated that IFN-gamma significantly inhibited the basal and LPS-induced
      HTRA1 expression in fibroblasts and macrophages, which are two major cells for
      HTRA1 production in RA. Importantly, the inhibitory effect of IFN-gamma on HTRA1
      expression was evidenced in collagen-induced arthritis (CIA) mouse models and in
      human RA synovial cells. In parallel with the enhanced CIA incidence and
      pathological changes in IFN-gamma-deficient mice, HTRA1 expression in the joint
      tissues was also increased as determined by real-time PCR and Western blots. IFN
      gamma deficiency increased the incidence of CIA and the pathological severity in
      mice. Neutralization of HTRA1 by Ab significantly reversed the enhanced CIA
      frequency and severity in IFN-gamma-deficient mice. Mechanistically, IFN-gamma
      negatively controls HTRA1 expression through activation of p38 MAPK/STAT1
      pathway. Dual luciferase reporter assay and chromatin immunoprecipitation
      analysis showed that STAT1 could directly bind to HTRA1 promoter after IFN-gamma
      stimulation. This study offers new insights into the molecular regulation of
      HTRA1 expression and its role in RA pathogenesis, which may have significant
      impact on clinical therapy for RA and possibly other HTRA1-related diseases,
      including osteoarthritis, age-related macular degeneration, and cancer. 

PMID- 24907346
TI  - Early lymphoid responses and germinal center formation correlate with lower viral
      load set points and better prognosis of simian immunodeficiency virus infection.
AB  - We have investigated the dynamics of germinal center (GC) formation in lymphoid
      tissues following acute SIV infection. SIV induces a marked follicular
      hyperplasia, associated with an aberrant accumulation of nonproliferating T
      follicular helper cells within GCs, but with an abundance of cells producing IL
      21, demonstrating that the mechanisms involved for these two events appear
      independent. IL-21-stimulated T follicular helper cells are considered a critical
      element for GC formation, a physiological process that seems dysregulated and
      excessive during HIV/SIV infection, contributing to lymphoid pathogenesis.
      However, the data suggest that the kinetics by which such GCs are formed may be
      an important predictor of the host-pathogen equilibrium, as early GC hyperplasia
      was associated with better control of viral replication. In contrast, monkeys
      undergoing fast disease progression upon infection exhibited an involution of GCs
      without local IL-21 production in GCs. These results provide important clues
      regarding GC-related hyperimmune responses in the context of disease progression
      within various individuals during HIV/SIV infection and may open novel
      therapeutic avenues to limit lymphoid dysfunction, postinfection. 

PMID- 24907347
TI  - Proliferation conditions promote intrinsic changes in NK cells for an IL-10
      response.
AB  - Constitutively found at high frequencies, the role for NK cell proliferation
      remains unclear. In this study, a shift in NK cell function from predominantly
      producing IFN-gamma, a cytokine with proinflammatory and antimicrobial functions,
      to producing the immunoregulatory cytokine IL-10 was defined during extended
      murine CMV infection. The response occurred at times subsequent to IL-12
      production, but the NK cells elicited acquired responsiveness to IL-12 and IL-21
      for IL-10 production. Because neither IL-12 nor IL-21 was required in vivo,
      however, additional pathways appeared to be available to promote NK cell IL-10
      expression. In vitro studies with IL-2 to support proliferation and in vivo
      adoptive transfers into murine CMV-infected mice demonstrated that NK cell
      proliferation and further division enhanced the change. In contrast to the
      sustained open profile of the IFN-gamma gene, NK cells responding to infection
      acquired histone modifications in the IL-10 gene indicative of changing from a
      closed to an open state. The IL-10 response to IL-12 was proliferation dependent
      ex vivo if the NK cells had not yet expanded in vivo but independent if they had.
      Thus, a novel role for proliferation in supporting changing innate cell function
      is reported. 

PMID- 24907348
TI  - Luminal microbes promote monocyte-stem cell interactions across a healthy colonic
      epithelium.
AB  - The intestinal epithelium forms a vital barrier between luminal microbes and the
      underlying mucosal immune system. Epithelial barrier function is maintained by
      continuous renewal of the epithelium and is pivotal for gut homeostasis.
      Breaching of the barrier causes mobilization of immune cells to promote
      epithelial restitution. However, it is not known whether microbes at the luminal
      surface of a healthy epithelial barrier influence immune cell mobilization to
      modulate tissue homeostasis. Using a mouse colonic mucosal explant model, we
      demonstrate that close proximity of luminal microbes to a healthy, intact
      epithelium results in rapid mucus secretion and movement of Ly6C(+)7/4(+)
      monocytes closer to epithelial stem cells. These early events are driven by the
      epithelial MyD88-signaling pathway and result in increased crypt cell
      proliferation and intestinal stem cell number. Over time, stem cell number and
      monocyte-crypt stem cell juxtapositioning return to homeostatic levels observed
      in vivo. We also demonstrate that reduced numbers of tissue Ly6C+ monocytes can
      suppress Lgr5EGFP+ stem cell expression in vivo and abrogate the response to
      luminal microbes ex vivo. The functional link between monocyte recruitment and
      increased crypt cell proliferation was further confirmed using a crypt-monocyte
      coculture model. This work demonstrates that the healthy gut epithelium mediates
      communication between luminal bacteria and monocytes, and monocytes can modulate
      crypt stem cell number and promote crypt cell proliferation to help maintain gut
      homeostasis.

PMID- 24907350
TI  - Appreciation, gratitude, and looking forward.

PMID- 24907351
TI  - Voltage-gated potassium channel antibody-associated limbic encephalitis.
AB  - We are emphasising the importance of considering a rare diagnosis, voltage-gated
      Potassium channel antibody-associated limbic encephalitis, in an 80-year-old
      gentleman who presented with memory impairment, seizure and hyponatraemia. He was
      found to have high titre of voltage-gated potassium channel antibodies in his
      serum. He was given high-dose steroids and he responded biochemically and
      clinically with marked improvement in symptomatology. 

PMID- 24907349
TI  - The relationship between adiposity-associated inflammation and coronary artery
      and abdominal aortic calcium differs by strata of central adiposity: The Multi
      Ethnic Study of Atherosclerosis (MESA).
AB  - Adipokines regulate metabolic processes linked to coronary artery (CAC) and
      abdominal aorta calcification (AAC). Because adipokine and other adiposity
      associated inflammatory marker (AAIM) secretions differ between visceral and
      subcutaneous adipose tissue, we hypothesized that central adiposity modifies
      associations between AAIMs and CAC and AAC. We evaluated 1878 MESA participants
      with complete measures of AAIMs, anthropometry, CAC, and AAC. Associations of
      AAIMs with CAC and AAC prevalence and severity were analyzed per standard
      deviation of predictors (SD) using log binomial and linear regression models. The
      waist-to-hip ratio (WHR) was dichotomized at median WHR values based on
      sex/ethnicity. CAC and AAC prevalence were defined as any calcium (Agatston score
      >0). Severity was defined as ln (Agatston score). Analyses examined interactions
      with WHR and were adjusted for traditional cardiovascular disease risk factors.
      Each SD higher interleukin-6 (IL-6), fibrinogen and CRP was associated with 5%
      higher CAC prevalence; and each SD higher IL-6 and fibrinogen was associated with
      4% higher AAC prevalence. Associations of IL-6 and fibrinogen with CAC severity,
      but not CAC prevalence, were significantly different among WHR strata. Median-and
      above WHR: each SD higher IL-6 was associated with 24.8% higher CAC severity.
      Below-median WHR: no association (p interaction=0.012). Median-and-above WHR:
      each SD higher fibrinogen was associated with 19.6% higher CAC severity. Below
      median WHR: no association (p interaction=0.034). Adiponectin, leptin, resistin,
      and tumor necrosis factor-alpha were not associated with CAC or AAC prevalence or
      severity. These results support findings that adiposity-associated inflammation
      is associated with arterial calcification, and further add that central adiposity
      may modify this association.

PMID- 24907352
TI  - Pilot study of use of the BioStar Optical ImmunoAssay GC point-of-care test for
      diagnosing gonorrhoea in men attending a genitourinary medicine clinic.

PMID- 24907353
TI  - miRror-Suite: decoding coordinated regulation by microRNAs.
AB  - MicroRNAs (miRNAs) are short, non-coding RNAs that negatively regulate post
      transcriptional mRNA levels. Recent data from cross-linking and
      immunoprecipitation technologies confirmed the combinatorial nature of the miRNA
      regulation. We present the miRror-Suite platform, developed to yield a robust and
      concise explanation for miRNA regulation from a large collection of
      differentially expressed transcripts and miRNAs. The miRror-Suite platform
      includes the miRror2.0 and Probability Supported Iterative miRror (PSI-miRror)
      tools. Researchers who performed large-scale transcriptomics or miRNA profiling
      experiments from cells and tissues will benefit from miRror-Suite. Our platform
      provides a concise, plausible explanation for the regulation of miRNAs in such
      complex settings. The input for miRror2.0 may include hundreds of differentially
      expressed genes or miRNAs. In the case of miRNAs as input, the algorithm seeks
      the statistically most likely set of genes regulated by this input.
      Alternatively, for a set of genes, the miRror algorithm seeks a collection of
      miRNAs that best explains their regulation. The miRror-Suite algorithm designates
      statistical criteria that were uniformly applied to a dozen miRNA-target
      prediction databases. Users select the preferred databases for predictions and
      numerous optional filters/parameters that restrict the search to the desired
      tissues, cell lines, level of expression and predictor scores. PSI-miRror is an
      advanced application for refining the input set by gradually enhancing the degree
      of pairing of the sets of miRNAs with the sets of targets. The iterations of PSI
      miRror probe the interlinked nature of miRNAs and targets within cells. miRror
      Suite serves experimentalists in facilitating the understanding of miRNA
      regulation through combinatorial- cooperative activity. The platform applies to
      human, mouse, rat, fly, worm and zebrafish. Database URL:
      http://www.mirrorsuite.cs.huji.ac.il. 

PMID- 24907355
TI  - Generation and characterization of a novel CYP2A13--transgenic mouse model.
AB  - CYP2A13, CYP2B6, and CYP2F1 are neighboring cytochrome P450 genes on human
      chromosome 19, and the enzymes that they encode overlap in substrate specificity.
      A CYP2A13/2B6/2F1-transgenic mouse, in which CYP2A13 and 2F1 are both expressed
      in the respiratory tract and CYP2B6 is expressed in the liver, was recently
      generated. We generated a CYP2A13 (only) transgenic mouse so that the specific
      activity of CYP2A13 can be determined. The CYP2B6 and CYP2F1 genes in the
      CYP2A13/2B6/2F1 genomic clone were inactivated via genetic manipulations, and
      CYP2A13 was kept intact. A CYP2A13 (only) transgenic (2A13-TG) mouse was
      generated using the engineered construct and then characterized to confirm
      transgene integrity and determine copy numbers. The 2A13-TG mice were normal in
      gross morphology, development, and fertility. As in the CYP2A13/2B6/2F1
      transgenic mouse, CYP2A13 expression in the 2A13-TG mouse was limited to the
      respiratory tract; in contrast, CYP2B6 and 2F1 proteins were not detected.
      Additional studies using the CYP2A13-humanized (2A13-TG/Cyp2abfgs-null) mouse
      produced by intercrossing between 2A13-TG and Cyp2abfgs-null mice confirmed that
      the transgenic CYP2A13 is active in the bioactivation of 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanone (NNK), a lung procarcinogen. The 2A13-TG mouse should be
      valuable for assessing specific roles of human CYP2A13 in xenobiotic toxicity in
      the respiratory tract. 

PMID- 24907356
TI  - JAK2V617F somatic mutation in the general population: myeloproliferative neoplasm
      development and progression rate.
AB  - Clinical significance of the JAK2V617F mutation in patients with a
      myeloproliferative neoplasm has been the target of intensive research in recent
      years. However, there is considerably uncertainty about prognosis in JAK2V617F
      positive individuals without overt signs of myeloproliferative disease. In this
      study, we tested the hypothesis that increased JAK2V617F somatic mutation burden
      is associated with myeloproliferative neoplasm progression rate in the general
      population. Among 49,488 individuals from the Copenhagen General Population
      Study, 63 (0.1%) tested positive for the JAK2V617F mutation in the time period
      2003-2008. Of these, 48 were available for re-examination in 2012. Level of
      JAK2V617F mutation burden was associated with myeloproliferative neoplasm
      progression rate, consistent with a biological continuum of increasing JAK2V617F
      mutation burden across increasing severity of myeloproliferative neoplasm from no
      disease (n=8 at re-examination) through essential thrombocythemia (n=20) and
      polycythemia vera (n=13) to primary myelofibrosis (n=7). Among those diagnosed
      with a myeloproliferative neoplasm only at re-examination in 2012, in the
      preceding years JAK2V617F mutation burden increased by 0.55% per year,
      erythrocyte volume fraction increased by 1.19% per year, and erythrocyte mean
      corpuscular volume increased by 1.25% per year, while there was no change in
      platelet count or erythropoietin levels. Furthermore, we established a JAK2V617F
      mutation burden cut-off point of 2% indicative of disease versus no disease;
      however, individuals with a mutation burden below 2% may suffer from a latent
      form of myeloproliferative disease revealed by a slightly larger spleen and/or
      slightly higher lactic acid dehydrogenase concentration compared to controls. Of
      all 63 JAK2V617F positive individuals, 48 were eventually diagnosed with a
      myeloproliferative neoplasm. 

PMID- 24907357
TI  - In vivo effects of horse and rabbit antithymocyte globulin in patients with
      severe aplastic anemia.
AB  - We recently reported that rabbit antithymocyte globulin was markedly inferior to
      horse antithymocyte globulin as a primary treatment for severe aplastic anemia.
      Here we expand on our findings in this unique cohort of patients. Rabbit
      antithymocyte globulin was detectable in plasma for longer periods than horse
      antithymocyte globulin; rabbit antithymocyte globulin in plasma retained
      functional capacity to bind to lymphocytes for up to 1 month, horse antithymocyte
      globulin for only about 2 weeks. In the first week after treatment there were
      much lower numbers of neutrophils in patients treated with rabbit antithymocyte
      globulin than in patients receiving horse antithymocyte globulin. Both
      antithymocyte globulins induced a "cytokine storm" in the first 2 days after
      administration. Compared with horse antithymocyte globulin, rabbit antithymocyte
      globulin was associated with higher levels of chemokine (C-C motif) ligand 4
      during the first 3 weeks. Besides a much lower absolute number and a lower
      relative frequency of CD4(+) T cells, rabbit antithymocyte globulin induced
      higher frequencies of CD4(+)CD38(+), CD3(+)CD4(-)CD8(-) T cells, and B cells than
      did horse antithymocyte globulin. Serum sickness occurred around 2 weeks after
      infusion of both types of antithymocyte globulin. Human anti-antithymocyte
      globulin antibodies, especially of the IgM subtype, correlated with serum
      sickness, which appeared concurrently with clearance of antithymocyte globulin in
      blood and with the production of cytokines. In conclusion, rabbit and horse
      antithymocyte globulins have very different pharmacokinetics and effects on
      neutrophils, lymphocyte subsets, and cytokine release. These differences may be
      related to their efficacy in suppressing the immune system and restoring
      hematopoiesis in bone marrow failure. Clinicaltrials.gov identifier: NCT00260689.

PMID- 24907358
TI  - Genetic characterization of acquired aplastic anemia by targeted sequencing.

PMID- 24907360
TI  - Recent results from the two Canadian breast screening trials.

PMID- 24907359
TI  - SETBP1 mutations in 106 patients with therapy-related myeloid neoplasms.

PMID- 24907361
TI  - The estimation of median nuchal translucency values between 10 and 14 weeks of
      pregnancy.
AB  - Nuchal translucency (NT) is a useful marker in antenatal screening for Down's
      syndrome in the late first trimester of pregnancy. NT measurements increase with
      increasing crown rump length (CRL) so multiple of the median (MoM) values are
      used to allow for this. Log-linear and log-quadratic regressions of NT in
      relation to CRL have previously been proposed to calculate MoM values. Using data
      on 288,079 women, these models were compared with a log-sigmoid regression. The
      log-linear regression overestimated the median NT above a CRL of 75 mm; for
      example, 1.9 mm versus 1.8 mm observed at 75-79 mm, and 2.0 mm versus 1.8 mm at
      80-84 mm. The log-quadratic regression underestimated the median NT below a CRL
      of 45 mm at 1.03 mm versus 1.2 mm observed. The sigmoid regression provided the
      best overall fit to the data across the range of CRL values (40-84 mm)
      corresponding to gestational ages of 76 to 99 days. The differences between the
      three models are small. If a log-linear regression appears to be a poor fit using
      local data, a log-sigmoid regression could be considered. 

PMID- 24907362
TI  - Inflammation and lipid profile in rheumatoid arthritis: bridging an apparent
      paradox.

PMID- 24907363
TI  - Translating research for health policy: researchers' perceptions and use of
      social media.
AB  - As the United States moves forward with health reform, the communication gap
      between researchers and policy makers will need to be narrowed to promote
      policies informed by evidence. Social media represent an expanding channel for
      communication. Academic journals, public health agencies, and health care
      organizations are increasingly using social media to communicate health
      information. For example, the Centers for Disease Control and Prevention now
      regularly tweets to 290,000 followers. We conducted a survey of health policy
      researchers about using social media and two traditional channels (traditional
      media and direct outreach) to disseminate research findings to policy makers.
      Researchers rated the efficacy of the three dissemination methods similarly but
      rated social media lower than the other two in three domains: researchers'
      confidence in their ability to use the method, peers' respect for its use, and
      how it is perceived in academic promotion. Just 14 percent of our participants
      reported tweeting, and 21 percent reported blogging about their research or
      related health policy in the past year. Researchers described social media as
      being incompatible with research, of high risk professionally, of uncertain
      efficacy, and an unfamiliar technology that they did not know how to use.
      Researchers will need evidence-based strategies, training, and institutional
      resources to use social media to communicate evidence.

PMID- 24907364
TI  - TAL effectors: tools for DNA targeting.
AB  - Xanthomonas phytopathogenic bacteria produce unique transcription activator-like
      effector (TALE) proteins that recognize and activate specific plant promoters
      through a set of tandem repeats. A unique TALE-DNA-binding code uses two
      polymorphic amino acids in each repeat to mediate recognition of specific
      nucleotides. The order of repeats determines effector's specificity toward the
      cognate nucleotide sequence of the sense DNA strand. Artificially designed TALE
      DNA-binding domains fused to nuclease or activation and repressor domains provide
      an outstanding toolbox for targeted gene editing and gene regulation in research,
      biotechnology and gene therapy. Gene editing with custom-designed TALE nucleases
      (TALENs) extends the repertoire of targeted genome modifications across a broad
      spectrum of organisms ranging from plants and insect to mammals. 

PMID- 24907365
TI  - Event-based text mining for biology and functional genomics.
AB  - The assessment of genome function requires a mapping between genome-derived
      entities and biochemical reactions, and the biomedical literature represents a
      rich source of information about reactions between biological components.
      However, the increasingly rapid growth in the volume of literature provides both
      a challenge and an opportunity for researchers to isolate information about
      reactions of interest in a timely and efficient manner. In response, recent text
      mining research in the biology domain has been largely focused on the
      identification and extraction of 'events', i.e. categorised, structured
      representations of relationships between biochemical entities, from the
      literature. Functional genomics analyses necessarily encompass events as so
      defined. Automatic event extraction systems facilitate the development of
      sophisticated semantic search applications, allowing researchers to formulate
      structured queries over extracted events, so as to specify the exact types of
      reactions to be retrieved. This article provides an overview of recent research
      into event extraction. We cover annotated corpora on which systems are trained,
      systems that achieve state-of-the-art performance and details of the community
      shared tasks that have been instrumental in increasing the quality, coverage and
      scalability of recent systems. Finally, several concrete applications of event
      extraction are covered, together with emerging directions of research. 

PMID- 24907367
TI  - MAGI: a Node.js web service for fast microRNA-Seq analysis in a GPU
      infrastructure.
AB  - SUMMARY: MAGI is a web service for fast MicroRNA-Seq data analysis in a graphics
      processing unit (GPU) infrastructure. Using just a browser, users have access to
      results as web reports in just a few hours->600% end-to-end performance
      improvement over state of the art. MAGI's salient features are (i) transfer of
      large input files in native FASTA with Qualities (FASTQ) format through drag-and
      drop operations, (ii) rapid prediction of microRNA target genes leveraging
      parallel computing with GPU devices, (iii) all-in-one analytics with novel
      feature extraction, statistical test for differential expression and diagnostic
      plot generation for quality control and (iv) interactive visualization and
      exploration of results in web reports that are readily available for publication.
      AVAILABILITY AND IMPLEMENTATION: MAGI relies on the Node.js JavaScript framework,
      along with NVIDIA CUDA C, PHP: Hypertext Preprocessor (PHP), Perl and R. It is
      freely available at http://magi.ucsd.edu.

PMID- 24907366
TI  - Structural variations in plant genomes.
AB  - Differences between plant genomes range from single nucleotide polymorphisms to
      large-scale duplications, deletions and rearrangements. The large polymorphisms
      are termed structural variants (SVs). SVs have received significant attention in
      human genetics and were found to be responsible for various chronic diseases.
      However, little effort has been directed towards understanding the role of SVs in
      plants. Many recent advances in plant genetics have resulted from improvements in
      high-resolution technologies for measuring SVs, including microarray-based
      techniques, and more recently, high-throughput DNA sequencing. In this review we
      describe recent reports of SV in plants and describe the genomic technologies
      currently used to measure these SVs. 

PMID- 24907368
TI  - Preserving biological heterogeneity with a permuted surrogate variable analysis
      for genomics batch correction.
AB  - MOTIVATION: Sample source, procurement process and other technical variations
      introduce batch effects into genomics data. Algorithms to remove these artifacts
      enhance differences between known biological covariates, but also carry potential
      concern of removing intragroup biological heterogeneity and thus any personalized
      genomic signatures. As a result, accurate identification of novel subtypes from
      batch-corrected genomics data is challenging using standard algorithms designed
      to remove batch effects for class comparison analyses. Nor can batch effects be
      corrected reliably in future applications of genomics-based clinical tests, in
      which the biological groups are by definition unknown a priori. RESULTS:
      Therefore, we assess the extent to which various batch correction algorithms
      remove true biological heterogeneity. We also introduce an algorithm, permuted
      SVA (pSVA), using a new statistical model that is blind to biological covariates
      to correct for technical artifacts while retaining biological heterogeneity in
      genomic data. This algorithm facilitated accurate subtype identification in head
      and neck cancer from gene expression data in both formalin-fixed and frozen
      samples. When applied to predict Human Papillomavirus (HPV) status, pSVA improved
      cross-study validation even if the sample batches were highly confounded with HPV
      status in the training set. AVAILABILITY AND IMPLEMENTATION: All analyses were
      performed using R version 2.15.0. The code and data used to generate the results
      of this manuscript is available from https://sourceforge.net/projects/psva.

PMID- 24907369
TI  - ABRA: improved coding indel detection via assembly-based realignment.
AB  - MOTIVATION: Variant detection from next-generation sequencing (NGS) data is an
      increasingly vital aspect of disease diagnosis, treatment and research. Commonly
      used NGS-variant analysis tools generally rely on accurately mapped short reads
      to identify somatic variants and germ-line genotypes. Existing NGS read mappers
      have difficulty accurately mapping short reads containing complex variation (i.e.
      more than a single base change), thus making identification of such variants
      difficult or impossible. Insertions and deletions (indels) in particular have
      been an area of great difficulty. Indels are frequent and can have substantial
      impact on function, which makes their detection all the more imperative. RESULTS:
      We present ABRA, an assembly-based realigner, which uses an efficient and
      flexible localized de novo assembly followed by global realignment to more
      accurately remap reads. This results in enhanced performance for indel detection
      as well as improved accuracy in variant allele frequency estimation. AVAILABILITY
      AND IMPLEMENTATION: ABRA is implemented in a combination of Java and C/C++ and is
      freely available for download at https://github.com/mozack/abra.

PMID- 24907370
TI  - The kinesin-13 KLP10A motor regulates oocyte spindle length and affects EB1
      binding without altering microtubule growth rates.
AB  - Kinesin-13 motors are unusual in that they do not walk along microtubules, but
      instead diffuse to the ends, where they remove tubulin dimers, regulating
      microtubule dynamics. Here we show that Drosophila kinesin-13 klp10A regulates
      oocyte meiosis I spindle length and is haplo-insufficient - KLP10A, reduced by
      RNAi or a loss-of-function P element insertion mutant, results in elongated and
      mispositioned oocyte spindles, and abnormal cortical microtubule asters and
      aggregates. KLP10A knockdown by RNAi does not significantly affect microtubule
      growth rates in oocyte spindles, but, unexpectedly, EB1 binding and unbinding are
      slowed, suggesting a previously unobserved role for kinesin-13 in mediating EB1
      binding interactions with microtubules. Kinesin-13 may regulate spindle length
      both by disassembling subunits from microtubule ends and facilitating EB1 binding
      to plus ends. We also observe an increased number of paused microtubules in
      klp10A RNAi knockdown spindles, consistent with a reduced frequency of
      microtubule catastrophes. Overall, our findings indicate that reduced kinesin-13
      decreases microtubule disassembly rates and affects EB1 interactions with
      microtubules, rather than altering microtubule growth rates, causing spindles to
      elongate and abnormal cortical microtubule asters and aggregates to form. 

PMID- 24907371
TI  - 'Peer pressure' in larval Drosophila?
AB  - Understanding social behaviour requires a study case that is simple enough to be
      tractable, yet complex enough to remain interesting. Do larval Drosophila meet
      these requirements? In a broad sense, this question can refer to effects of the
      mere presence of other larvae on the behaviour of a target individual. Here we
      focused in a more strict sense on 'peer pressure', that is on the question of
      whether the behaviour of a target individual larva is affected by what a
      surrounding group of larvae is doing. We found that innate olfactory preference
      of a target individual was neither affected (i) by the level of innate olfactory
      preference in the surrounding group nor (ii) by the expression of learned
      olfactory preference in the group. Likewise, learned olfactory preference of a
      target individual was neither affected (iii) by the level of innate olfactory
      preference of the surrounding group nor (iv) by the learned olfactory preference
      the group was expressing. We conclude that larval Drosophila thus do not take
      note of specifically what surrounding larvae are doing. This implies that in a
      strict sense, and to the extent tested, there is no social interaction between
      larvae. These results validate widely used en mass approaches to the behaviour of
      larval Drosophila. 

PMID- 24907372
TI  - The energy costs of wading in water.
AB  - Studies measuring the energy costs of wading in water have been limited to higher
      walking speeds in straight lines, in deep water. However, much foraging in water,
      by both humans and other primates, is conducted in the shallows and at low speeds
      of locomotion that include elements of turning, as befits searching for cryptic
      or hidden foods within a patch. The present study brings together data on the
      rate of oxygen consumption during wading by humans from previous studies, and
      augments these with new data for wading in shallower depths, with slower and more
      tortuous walking, to obtain a better understanding both of the absolute costs of
      wading in typical scenarios of aquatic foraging and of how the cost of wading
      varies as a function of water depth and speed of locomotion. Previous and present
      data indicate that, at low speeds, wading has a similar energetic cost to walking
      on land, particularly at lower water depths, and only at higher speeds is the
      cost of wading noticeably more expensive than when water is absent. This is
      probably explained by the relatively small volume of water that must be displaced
      during locomotion in shallow waters coupled with the compensating support to the
      limbs that the water affords. The support to the limbs/body provided by water is
      discussed further, in the context of bipedal locomotion by non-human primates
      during wading. 

PMID- 24907373
TI  - Reality check: the cost-effectiveness of removing body checking from youth ice
      hockey.
AB  - BACKGROUND/AIM: The risk of injury among Pee Wee (ages 11-12 years) ice hockey
      players in leagues that allow body checking is threefold greater than in leagues
      that do not allow body checking. We estimated the cost-effectiveness of a no body
      checking policy versus a policy that allows body checking in Pee Wee ice hockey.
      METHODS: Cost-effectiveness analysis alongside a prospective cohort study during
      the 2007-2008 season, including players in Quebec (n=1046), where policy did not
      allow body checking, and in Alberta (n=1108), where body checking was allowed.
      Injury incidence rates (injuries/1000 player-hours) and incidence proportions
      (injuries/100 players), adjusted for cluster using Poisson regression, allowed
      for standardised comparisons and meaningful translation to community
      stakeholders. Based on Alberta fee schedules, direct healthcare costs (physician
      visits, imaging, procedures) were adjusted for cluster using bootstrapping. We
      examined uncertainty in our estimates using cost-effectiveness planes. RESULTS:
      Associated with significantly higher injury rates, healthcare costs where policy
      allowed body checking were over 2.5 times higher than where policy disallowed
      body checking ($C473/1000 player-hours (95% CI $C358 to $C603) vs $C184/1000
      player-hours (95% CI $C120 to $C257)). The difference in costs between provinces
      was $C289/1000 player-hours (95% CI $C153 to $C432). Projecting results onto
      Alberta Pee Wee players registered in the 2011-2012 season, an estimated 1273
      injuries and $C213 280 in healthcare costs would be avoided during just one
      season with the policy change. CONCLUSION: Our study suggests that a policy
      disallowing body checking in Pee Wee ice hockey is cost-saving (associated with
      fewer injuries and lower costs) compared to a policy allowing body checking. As
      we did not account for long-term outcomes, our results underestimate the economic
      impact of these injuries.

PMID- 24907374
TI  - What fooled us in the knee may trip us up in the hip: lessons from arthroscopy.

PMID- 24907375
TI  - GP is found guilty of negligence in failing to spot meningitis in 42 year old
      patient.

PMID- 24907376
TI  - The pro-factor D cleaving activity of MASP-1/-3 is not required for alternative
      pathway function.

PMID- 24907377
TI  - Comment on "the pro-factor D cleaving activity of MASP-1/-3 is not required for
      alternative pathway function".

PMID- 24907378
TI  - IL-2: the first effective immunotherapy for human cancer.
AB  - The ability of IL-2 to expand T cells with maintenance of functional activity has
      been translated into the first reproducible effective human cancer
      immunotherapies. The administration of IL-2 can lead to durable, complete, and
      apparently curative regressions in patients with metastatic melanoma and renal
      cancer. The growth of large numbers of tumor-infiltrating lymphocytes with in
      vitro anti-cancer activity in IL-2 has led to the development of cell transfer
      therapies that are highly effective in patients with melanoma. The genetic
      modification of T cells with genes encoding alphabeta TCRs or chimeric Ag
      receptors and the administration of these cells after expansion in IL-2 have
      extended effective cell transfer therapy to other cancer types. 

PMID- 24907381
TI  - Frequency of acute respiratory illnesses and circulation of respiratory viruses
      in households with children over 3 surveillance seasons.
AB  - BACKGROUND: The household has traditionally been the site for studying acute
      respiratory illnesses (ARIs). Most studies were conducted many years ago, and
      more broadly sensitive laboratory methods to determine ARI etiology are now
      available. METHODS: We recruited and followed households with children over 3
      annual surveillance periods and collected respiratory tract specimens from
      subjects with reported ARI. Virus etiology was determined by real-time reverse
      transcription polymerase chain reaction (RT-PCR) analysis. RESULTS: Individuals
      in larger households (defined as households with >4 members) and those in
      households with children aged <5 years had significantly higher ARI frequencies
      than others. ARI frequency generally declined with increasing age. Virus etiology
      was most likely to be determined in young children, who were also most likely to
      have virus coinfection. Overall, 16% of ARIs with 1 virus identified had >=1
      coinfecting virus. Rhinoviruses and coronaviruses were the most frequently
      identified agents of ARI in all age categories. Influenza virus and adenovirus
      were less frequently identified but were most likely to cause ARI that required
      medical attention. CONCLUSIONS: Longitudinal studies in families remain a
      valuable way to study respiratory infections. RT-PCR has increased the
      sensitivity of virus detection, including coinfecting viruses, and expanded our
      ability to detect viruses now known to cause ARI.

PMID- 24907379
TI  - Type I interferon in the pathogenesis of lupus.
AB  - Investigations of patients with systemic lupus erythematosus have applied
      insights from studies of the innate immune response to define IFN-I, with IFN
      alpha as the dominant mediator, as central to the pathogenesis of this prototype
      systemic autoimmune disease. Genetic association data identify regulators of
      nucleic acid degradation and components of TLR-independent, endosomal TLR
      dependent, and IFN-I-signaling pathways as contributors to lupus disease
      susceptibility. Together with a gene expression signature characterized by IFN-I
      induced gene transcripts in lupus blood and tissue, those data support the
      conclusion that many of the immunologic and pathologic features of this disease
      are a consequence of a persistent self-directed immune reaction driven by IFN-I
      and mimicking a sustained antivirus response. This expanding knowledge of the
      role of IFN-I and the innate immune response suggests candidate therapeutic
      targets that are being tested in lupus patients. 

PMID- 24907382
TI  - Diminished systemic and antigen-specific type 1, type 17, and other
      proinflammatory cytokines in diabetic and prediabetic individuals with latent
      Mycobacterium tuberculosis infection.
AB  - BACKGROUND: Diabetes mellitus type 2 (DM) is known to be a major risk factor for
      the development of active tuberculosis, although its influence on latent
      Mycobacterium tuberculosis infection (hereafter, "latent infection") remains
      poorly characterized. METHODS: We examined circulating plasma cytokine levels in
      individuals with latent infection with DM or pre-DM (ie, intermediate
      hyperglycemia) and compared them to levels in patients with latent infection and
      normal glycemic control. RESULTS: In persons with DM or pre-DM, latent infection
      is characterized by diminished circulating levels of type 1 (interferon gamma,
      interleukin 2, and tumor necrosis factor alpha) and type 17 (interleukin 17F)
      cytokines. This was associated with decreased systemic levels of other
      proinflammatory cytokines (interleukin 1beta and interleukin 18) and the
      antiinflammatory cytokine interleukin 10 but not with decreased systemic levels
      of type 2 cytokines. Moreover, latently infected individuals with DM had
      diminished levels of spontaneous and M. tuberculosis antigen-specific levels of
      type 1 and type 17 cytokines when antigen-stimulated whole blood was examined.
      Finally, there was no significant correlation between the levels of any of the
      cytokines measured (with the exception of interleukin 22) with hemoglobin A1c
      levels. CONCLUSIONS: Our data reveal that latent infection in the presence of DM
      or pre-DM, is characterized by diminished production of cytokines, implicated in
      the control of M. tuberculosis activation, allowing for a potential immunological
      mechanism that could account for the increased risk of active tuberculosis in
      latently infected individuals with DM.

PMID- 24907383
TI  - High nasopharyngeal pneumococcal density, increased by viral coinfection, is
      associated with invasive pneumococcal pneumonia.
AB  - BACKGROUND: We identified factors associated with pneumococcal colonization, high
      colonization density, and invasive pneumococcal pneumonia among patients
      hospitalized with acute lower respiratory tract infections (ALRTIs). METHODS: In
      2010, 4025 cases were enrolled in surveillance in South Africa. A total of 969 of
      4025 systematically selected nasopharyngeal-oropharyngeal specimens (24%) were
      tested for respiratory viruses and Streptococcus pneumoniae by real-time
      polymerase chain reaction. Of these, 749 (77%) had blood tested for S.
      pneumoniae. RESULTS: Pneumococcal colonization was detected in 55% of cases (534
      of 969). On multivariable analysis that controlled for age and tuberculosis
      treatment, infection with influenza virus (adjusted odds ratio [OR], 2.2; 95%
      confidence interval [CI], 1.1-4.5), adenovirus (adjusted OR, 1.7; 95% CI, 1.1
      2.7), rhinovirus (adjusted OR, 1.6; 95% CI, 1.1-2.3), and human immunodeficiency
      virus (HIV; adjusted OR, 1.6; 95% CI, 1.1-2.4) were associated with pneumococcal
      colonization. High colonization density was associated with respiratory virus
      coinfection (adjusted OR, 1.7; 95% CI, 1.1-2.6) and invasive pneumococcal
      pneumonia (adjusted OR, 2.3; 95% CI, 1.3-4.0), after adjustment for age and sex.
      Seven percent (52 of 749) had pneumococci detected in blood. On multivariable
      analysis among colonized cases, invasive pneumococcal pneumonia was associated
      with HIV (adjusted OR, 3.2; 95% CI, 1.4-7.5), influenza virus (adjusted OR, 8.2;
      95% CI, 2.7-25.0), high colonization density (adjusted OR, 18.7; 95% CI, 2.3
      155.1), and >=5 days of hospitalization (adjusted OR, 3.7; 95% CI, 1.7-8.2).
      CONCLUSIONS: Respiratory virus infection was associated with elevated
      colonization density and, in turn, invasive pneumococcal pneumonia.

PMID- 24907384
TI  - Interferon gamma-induced protein 10 kinetics in treatment-naive versus treatment
      experienced patients receiving interferon-free therapy for hepatitis C virus
      infection: implications for the innate immune response.
AB  - We measured interferon gamma-induced protein 10 (IP-10) levels in 428 patients at
      baseline, week 1, and week 2 of all-oral treatment for hepatitis C virus (HCV)
      infection. An increased baseline IP-10 level was associated with a T allele in
      the IL28B gene, an increased alanine aminotransferase level in treatment-naive
      but not experienced patients, and an increased body mass index. At week 1, the
      mean decline in plasma IP-10 levels was the same in treatment-naive and treatment
      experienced patients (-49%), whereas during week 2 the mean decline in IP-10
      levels in treatment-naive patients (-14%) was significantly larger than in
      treatment-experienced patients (-2%; P = .0176). IP-10 thus may be a surrogate
      marker of the rate of intracellular viral replication complex decay. 

PMID- 24907385
TI  - Flex-rigid pleuroscopy under local anesthesia in patients with dry pleural
      dissemination on radiography.
AB  - OBJECTIVE: Medical thoracoscopy using a flex-rigid pleuroscope under local
      anesthesia is a recent diagnostic procedure for malignant pleural disease.
      Although most previous studies have reported its usefulness, especially in wet
      pleural dissemination, the feasibility of flex-rigid pleuroscopy in patients with
      dry pleural dissemination is not well established.We assessed the diagnostic
      performance of flex-rigid pleuroscopy under local anesthesia in patients
      suspected of dry pleural dissemination on radiography. METHODS: The pleuroscopic
      parameters of all patients (n = 56) who underwent flex-rigid pleuroscopy at the
      National Cancer Center Hospital from October 2011 to September 2013 were
      retrospectively reviewed. Those with computed tomography findings of asymmetric
      pleural thickening or pleural nodules without pleural effusion (dry group, n =
      16) were compared with the remaining patients with pleural effusion (wet group).
      RESULTS: The dry group consisted of eight men and eight women, with a median age
      of 61 years (range, 48-79 years). The definitive diagnoses were adenocarcinoma (n
      = 10), mesothelioma (n = 2) and chronic inflammation (n = 3). The diagnostic
      accuracy was 93.8% (15/16). Only two minor complications were observed: mild
      chest pain (n = 1) and transient hypoxia (n = 1). No major complications such as
      pneumothorax were observed. The mean duration of post-operative chest tube
      drainage in the dry group was 2.31 +/- 2.26 days. Complications, operation
      duration and diagnostic accuracy did not statistically differ between the two
      groups. CONCLUSIONS: Flex-rigid pleuroscopy under local anesthesia can be a well
      tolerated diagnostic procedure for radiographic dry pleural dissemination with
      respect to diagnostic yield and complications.

PMID- 24907387
TI  - Food and Drug Administration responds to pressure for expanded drug access.

PMID- 24907388
TI  - Genomic testing: a struggle for oncologists.

PMID- 24907389
TI  - Melanoma treatment's changing landscape.

PMID- 24907390
TI  - Cancer prognosis: role of BMI and fat tissue.

PMID- 24907392
TI  - Interactions of pentacyclic triterpene acids with cardiolipins and related
      phosphatidylglycerols in model systems.
AB  - Pentacyclic triterpene acids (PTAs): betulinic (BAc), oleanolic (Ola) and ursolic
      (Urs) are potent pharmaceuticals applied in the therapy of cancer and bacterial
      infections. The mechanism of PTA action is multifactor, but the important step is
      their interaction with the lipids of mitochondrial and bacterial membranes. In
      our studies we applied the Langmuir monolayer technique to investigate the
      interactions between PTAs and cardiolipins (CLs) and phosphatidylglycerols (PGs).
      We applied two different mammalian mitochondrial CLs and one species extracted
      from the membrane of Escherichia coli. For comparison we performed the same
      experiments on the systems containing PTAs and 3 PGs strictly correlated
      structurally to the applied CLs. Our studies proved that PTAs can disturb the
      organization of CL-rich domains and affect the bacterial membrane fluidity by the
      interactions with phosphatidylglycerols, so anionic phospholipids are the targets
      of their membrane action. The thermodynamic interpretation of the results
      indicated that Urs has the highest membrane disorganizing potential among the 3
      studied PTAs. The studies performed on model systems proved also that BAc can
      discriminate over structurally similar animal cardiolipin species, interacts
      specifically with BHCL - the main mammalian CL and can disturb its organization
      in the membrane. In contrast, Ola and Urs are much active as far as the
      interaction with bacterial CLs and PGs is concerned. 

PMID- 24907393
TI  - Defective pre-mRNA splicing in PKD1 due to presumed missense and synonymous
      mutations causing autosomal dominant polycystic disease.
AB  - Autosomal dominant polycystic kidney disease is the most common human monogenic
      disorder and is caused by mutations in the PKD1 or PKD2 genes. Most patients with
      the disease present mutations in PKD1, and a considerable number of these
      alterations are single base substitutions within the coding sequence that are
      usually predicted to lead to missense or synonymous mutations. There is growing
      evidence that some of these mutations can be detrimental by affecting the pre
      mRNA splicing process. The aim of our study was to test PKD1 mutations, described
      as missense or synonymous in the literature or databases, for their effects on
      exon inclusion. Bioinformatics tools were used to select mutations with a
      potential effect on pre-mRNA splicing. Mutations were experimentally tested using
      minigene assays. Exons and adjacent intronic sequences were PCR-amplified and
      cloned in the splicing reporter minigene, and selected mutations were introduced
      by site-directed mutagenesis. Minigenes were transfected into kidney derived cell
      lines. RNA from cultured cells was analyzed by RT-PCR and DNA sequencing.
      Analysis of thirty-three PKD1 exonic mutations revealed three mutations that
      induce splicing defects. The substitution c.11156G>A, previously predicted as
      missense mutation p.R3719Q, abolished the donor splice site of intron 38 and
      resulted in the incorporation of exon 38 with 117bp of intron 38 and skipping of
      exon 39. Two synonymous variants, c.327A>T (p.G109G) and c.11257C>A (p.R3753R),
      generated strong donor splice sites within exons 3 and 39 respectively, resulting
      in incorporation of incomplete exons. These three nucleotide substitutions
      represent the first PKD1 exonic mutations that induce aberrant mRNAs. Our results
      strengthen the importance to evaluate the consequences of presumed missense and
      synonymous mutations at the mRNA level. 

PMID- 24907394
TI  - Draft genome sequence of Microbulbifer elongatus strain HZ11, a brown seaweed
      degrading bacterium with potential ability to produce bioethanol from alginate.
AB  - Microbulbifer elongatus strain HZ11, was a new strain of M. elongates DSM
      6810(T), which has the ability to degrade brown seaweeds such as Laminaria
      japonica into single cell detritus particles. Here we report a high quality draft
      genome of M. elongatus strain HZ11, which comprises 4,223,108bp in 9 contigs with
      the G+C content of 56.70%. A total of 3293 protein-coding sequences were
      predicted, including nine alginate lyases (EC 4.2.2.3), five agarases (EC
      3.2.1.81), 2-dehydro-3-deoxygluconate kinase (EC 2.7.1.45) and all enzymes
      involved in the Entner-Doudoroff pathway. Our results suggest that strain HZ11
      has the potential ability to produce bioethanol from alginate with moderate
      genetic modification, which may significantly increase the yield of bioethanol
      from brown seaweed and the utilization rate of brown seaweeds.

PMID- 24907395
TI  - microRNA-7: a tumor suppressor miRNA with therapeutic potential.
AB  - microRNAs are a family of endogenous, short, non-coding RNAs that play critical
      roles in regulating gene expression for key cellular processes in normal and
      abnormal physiology. microRNA-7 is a 23 nucleotide miRNA whose expression is
      tightly regulated and restricted predominantly to the brain, spleen and pancreas.
      Reduced levels of miR-7 have been linked to the development of cancer and
      metastasis. As a tumor suppressor, miR-7 functions to co-ordinately downregulate
      a number of direct (e.g. the epidermal growth factor receptor) and indirect (e.g.
      phospho-Akt) growth promoting targets to decrease tumor growth in vitro and in
      vivo. In addition, miR-7 can increase the sensitivity of treatment-resistant
      cancer cells to therapeutics and inhibit metastasis. These data suggest that
      replacement of miR-7 ('miRNA replacement therapy') for specific human cancers
      could represent a new treatment approach. This article is part of a Directed
      Issue entitled: The Non-coding RNA Revolution. 

PMID- 24907396
TI  - Physical and functional interaction of the proto-oncogene EVI1 and tumor
      suppressor gene HIC1 deregulates Bcl-xL mediated block in apoptosis.
AB  - Ecotropic viral integration site 1 was originally identified as a retroviral
      integration site in murine leukemias. Several studies have established ecotropic
      viral integration site 1 as both a transcription factor and an interacting
      partner that presumably regulates gene expression. Using coimmunoprecipitation
      and fluorescence resonance energy transfer analysis, we found that the N-terminal
      domain of hypermethylated in cancer 1 interacts with the proximal set of zinc
      fingers of ecotropic viral integration site 1. This interaction not only
      abolishes the DNA binding activity of ecotropic viral integration site 1 but also
      disrupts the transcriptional activity of an anti-apoptotic gene promoter
      selectively targeted by ecotropic viral integration site 1. By using flow
      cytometry and western blotting, here we show that hypermethylated in cancer 1 can
      deregulate ecotropic viral integration site 1-mediated blockage of apoptosis. We
      hypothesize that therapeutic upregulation of hypermethylated in cancer 1 may
      provide an important means of targeting ecotropic viral integration site 1
      positive cancers. 

PMID- 24907397
TI  - Hyperglycemia-induced oxidative stress induces apoptosis by inhibiting PI3
      kinase/Akt and ERK1/2 MAPK mediated signaling pathway causing downregulation of 8
      oxoG-DNA glycosylase levels in glial cells.
AB  - Glial cells are very important for normal brain function and alterations in their
      activity due to hyperglycemia, could contribute to diabetes-related cognitive
      dysfunction. Oxidative insults often cause rapid changes in almost all cells
      including glial cells. However, pathophysiologic mechanisms that lead to diabetic
      complications are not completely elucidated. Therefore, we examined whether
      elevated glucose levels directly or indirectly disrupt antioxidant defense
      mechanisms causing alterations in signaling pathways, cell cycle dysregulation,
      and reactive oxygen/nitrogen species-mediated apoptosis in glial cells. Findings
      of this study demonstrated that exposure of glial cells to high glucose markedly
      induces cellular and molecular injuries, as evidenced by elevated levels of
      reactive oxygen/nitrogen species, biomolecules damage, cell cycle dysregulation,
      decrease in antioxidant enzymes, and decrease in cell viability. Pretreatment of
      cells with N-acetyl-L-cysteine reduced high glucose-induced cytotoxicity by
      increasing the levels of antioxidant enzymes, and decreasing the number of
      apoptotic cells. Further, at molecular level high glucose treatment resulted in a
      significant increase in phosphorylation of Akt, MAPKs, tuberin, down regulation
      of 8-oxoG-DNA glycosylase and increase in 8-hydroxydeoxyguanosine accumulations.
      Pretreatment of cells with N-acetyl-L-cysteine, phosphatidylinositol3-kinase/Akt
      and ERK1/2 inhibitors completely abolished the apoptotic effects of high glucose.
      Moreover, N-acetyl-L-cysteine significantly inhibited reactive oxygen/nitrogen
      species generation, elevated antioxidants levels, inhibited Akt, ERK1/2, tuberin
      phosphorylation, decreased 8-hydroxydeoxyguanosine accumulation and upregulated 8
      oxoG-DNA glycosylase expression. Our results demonstrate that high glucose
      induces apoptosis and inhibits proliferation of glial cells, which may be
      mediated by the phosphorylation of tuberin, down regulation of 8-oxoG-DNA
      glycosylase and 8-hydroxydeoxyguanosine accumulation via activation of Akt and
      ERK1/2MAPK pathways.

PMID- 24907398
TI  - Rare cancers.

PMID- 24907400
TI  - ALS-associated peripherin spliced transcripts form distinct protein inclusions
      that are neuroprotective against oxidative stress.
AB  - Intracellular proteinaceous inclusions are well-documented hallmarks of the fatal
      motor neuron disorder amyotrophic lateral sclerosis (ALS). The pathological
      significance of these inclusions remains unknown. Peripherin, a type III
      intermediate filament protein, is upregulated in ALS and identified as a
      component within different types of ALS inclusions. The formation of these
      inclusions may be associated with abnormal peripherin splicing, whereby an
      increase in mRNA retaining introns 3 and 4 (Per-3,4) leads to the generation of
      an aggregation-prone isoform, Per-28. During the course of evaluating peripherin
      filament assembly in SW-13 cells, we identified that expression of both Per-3,4
      and Per-28 transcripts formed inclusions with categorically distinct morphology:
      Per-3,4 was associated with cytoplasmic condensed/bundled filaments, small
      inclusions (<10MUM), or large inclusions (>=10MUM); while Per-28 was associated
      with punctate inclusions in the nucleus and/or cytoplasm. We found temporal and
      spatial changes in inclusion morphology between 12 and 48h post-transfected
      cells, which were accompanied by unique immunofluorescent and biochemical changes
      of other ALS-relevant proteins, including TDP-43 and ubiquitin. Despite mild
      cytotoxicity associated with peripherin transfection, Per-3,4 and Per-28
      expression increased cell viability during H2O2-mediated oxidative stress in
      BE(2)-M17 neuroblastoma cells. Taken together, this study shows that ALS
      associated peripherin isoforms form dynamic cytoplasmic and intranuclear
      inclusions, effect changes in local endogenous protein expression, and afford
      cytoprotection against oxidative stress. These findings may have important
      relevance to understanding the pathophysiological role of inclusions in ALS. 

PMID- 24907401
TI  - Cytokine signaling by grafted neuroectodermal stem cells rescues motoneurons
      destined to die.
AB  - Following an injury to their axons close to the cell body, adult motoneurons
      generally die. This type of injury, typically caused by avulsion of the spinal
      ventral root, initiates the activation of astrocytes and microglial cells and the
      extracellular space becomes loaded with excessive amounts of excitotoxic
      glutamate. We have provided evidence that, following ventral root avulsion and
      reimplantation, murine embryonic neuroectodermal stem cells (NE-GFP-4C) grafted
      into the rat spinal cord rescue the vast majority of the motoneurons that would
      otherwise die, and enable them to reinnervate peripheral targets. Stem cell
      grafts produced the modulatory cytokines IL-1-alpha, IL-6, IL-10, TNF-alpha and
      MIP-1-alpha, but not neurotrophic factors. The neurons and astrocytes in the
      ventral horn of grafted animals also produced IL-6 and MIP-1-alpha, indicating a
      strong interaction between the graft and the host tissue. The infusion of
      function-blocking antibodies against all cytokines into the grafted cords
      completely abolished their motoneuron-rescuing effect, while neutralization of
      only IL-10 suggested its strong effectivity as concerns motoneuron survival and a
      milder effect on reinnervation. It is suggested that, apart from the anti
      inflammatory function of IL-10, the pro-inflammatory cytokines produced exert a
      strong modulatory function in the CNS, promoting the prevention of neuronal cell
      death. 

PMID- 24907402
TI  - Electrical properties of kisspeptin neurons and their regulation of GnRH neurons.
AB  - Kisspeptin neurons are critical components of the neuronal network controlling
      the activity of the gonadotropin-releasing hormone (GnRH) neurons. A variety of
      genetically-manipulated mouse models have recently facilitated the study of the
      electrical activity of the two principal kisspeptin neuron populations located in
      the rostral periventricular area of the third ventricle (RP3V) and arcuate
      nucleus (ARN) in acute brain slices. We discuss here the mechanisms and pathways
      through which kisspeptin neurons regulate GnRH neuron activity. We then examine
      the different kisspeptin-green fluorescent protein mouse models being used for
      kisspeptin electrophysiology and the data obtained to date for RP3V and ARN
      kisspeptin neurons. In light of these new observations on the spontaneous firing
      rates, intrinsic membrane properties, and neurotransmitter regulation of
      kisspeptin neurons, we speculate on the physiological roles of the different
      kisspeptin populations. 

PMID- 24907399
TI  - LRRK2, a puzzling protein: insights into Parkinson's disease pathogenesis.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a large, ubiquitous protein of unknown
      function. Mutations in the gene encoding LRRK2 have been linked to familial and
      sporadic Parkinson's disease (PD) cases. The LRRK2 protein is a single
      polypeptide that displays GTPase and kinase activity. Kinase and GTPase domains
      are involved in different cellular signaling pathways. Despite several
      experimental studies associating LRRK2 protein with various intracellular
      membranes and vesicular structures such as endosomal/lysosomal compartments, the
      mitochondrial outer membrane, lipid rafts, microtubule-associated vesicles, the
      golgi complex, and the endoplasmic reticulum its broader physiologic function(s)
      remain unidentified. Additionally, the cellular distribution of LRRK2 may
      indicate its role in several different pathways, such as the ubiquitin-proteasome
      system, the autophagic-lysosomal pathway, intracellular trafficking, and
      mitochondrial dysfunction. This review discusses potential mechanisms through
      which LRRK2 may mediate neurodegeneration and cause PD. 

PMID- 24907403
TI  - A randomized, double-blind, placebo-controlled trial and open-label extension
      study to evaluate the efficacy and safety of pregabalin in the treatment of
      neuropathic pain associated with human immunodeficiency virus neuropathy.
AB  - The objective of these studies was to assess the efficacy and safety of
      pregabalin in the treatment of human immunodeficiency virus (HIV)-associated
      neuropathic pain. Patients with HIV-associated distal sensory polyneuropathy
      (DSP) were randomized to treatment with flexible-dose pregabalin (150-600 mg/day)
      or placebo for 17 weeks in a single-blind, placebo lead-in, randomized, double
      blind, parallel-group, placebo-controlled multinational trial. The primary
      efficacy outcome was the change in mean pain score on an 11-point numeric rating
      scale (NRS) from baseline to study endpoint. Participants who completed this
      trial were invited to participate in a 6-month open-label extension study with
      pregabalin. Of the 377 patients enrolled in the randomized controlled trial
      (pregabalin, n=183; placebo, n=194), 68.4% completed treatment. In the open-label
      extension, 217 patients were treated and 59.4% completed treatment. Both studies
      were terminated by the sponsor after a preplanned interim analysis indicated
      trial futility. At endpoint, the change from baseline in least-squares mean NRS
      pain scores in the intent-to-treat population was -2.04 for pregabalin versus 
      2.11 for placebo (P=.709). There were no significant differences between the
      pregabalin and placebo groups in the secondary efficacy measures. Incidence of
      adverse events was lower than seen in previous pregabalin studies. Overall, this
      trial did not show pregabalin to be more efficacious than placebo in treating HIV
      associated DSP. Studies such as these, which fail to support their primary
      hypotheses, may be important in informing the methodology of future trials,
      especially when novel approaches to limit variability in the control group are
      included. ClinicalTrials.gov identifiers: NCT01049217 and NCT01145417.

PMID- 24907405
TI  - Suppression of bone marrow-derived microglia in the amygdala improves anxiety
      like behavior induced by chronic partial sciatic nerve ligation in mice.
AB  - Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and
      allodynia, and emotional abnormalities such as anxiety and depression. Although
      spinal cord microglia are involved in abnormal sensitivity to neuropathic pain,
      no previous studies have examined the mechanism of neuropathic pain-induced
      anxiety. Here, we examined the involvement of bone marrow (BM)-derived microglia
      aggregated in the amygdalae of mice with chronic neuropathic pain in the
      development of anxiety-like behavior. We prepared partial sciatic nerve ligations
      (PSNL) in mice that received bone marrow transplantation from green fluorescent
      protein (GFP)-Tg mice after irradiation with head protection, and examined GFP
      positive microglia in the central nuclei of the amygdalae (CeA). On day 28 after
      PSNL, BM-derived microglia aggregated in the CeA concurrent with anxiety-like
      behavior. BM-derived microglia in the CeA highly expressed interleukin (IL)-1beta
      and C-C chemokine receptor type 2 (CCR2). In addition, neurons in the CeA highly
      expressed monocyte chemotactic protein-1 (MCP-1), a ligand for CCR2, in PSNL
      treated mice compared to sham-operated mice, suggesting that the MCP-1/CCR2 axis
      is involved in the recruitment of BM-derived microglia. Oral administration of a
      CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and
      successfully reversed the anxiety-like behavior and hypersensitivity to
      mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1beta receptor
      antagonist directly into the CeA successfully reversed the anxiety-like behavior
      in the PSNL-treated mice even though the neuropathic pain persisted. These
      results suggest that the recruitment of BM-derived microglia to the CeA via the
      MCP-1/CCR2 axis and neuron-microglia interactions might be important in the
      pathogenesis of neuropathic pain-induced anxiety. 

PMID- 24907406
TI  - An SCN9A variant, known to cause pain, is now found to cause itch.

PMID- 24907404
TI  - Inflammation and inflammatory control in interstitial cystitis/bladder pain
      syndrome: Associations with painful symptoms.
AB  - Toll-like receptors (TLR) are known to play a role in chronic pain, from animal
      models and limited research in humans, but their role in interstitial
      cystitis/bladder pain syndrome (IC/BPS) is unknown. Similarly, alterations of the
      hypothalamic-pituitary-adrenal axis have been reported in some pain conditions.
      Our objectives were to identify inflammatory processes that might distinguish
      individuals with IC/BPS from healthy controls (HC) and to examine their
      associations with IC/BPS symptoms. Female participants (58IC/BPS patients and
      28HCs) completed pain and urinary symptom questionnaires and collected saliva for
      cortisol as part of the Multidisciplinary Approach to Pelvic Pain study.
      Inflammatory cytokines were assayed in plasma, and in TLR-2- and TLR-4-stimulated
      peripheral blood mononuclear cells. Controlling for BMI and negative affect,
      between-group differences were analyzed by general linear models, and
      relationships between symptoms and inflammatory variables were analyzed by
      regression. Compared to HCs, IC/BPS patients had higher levels of plasma
      interleukin-6 (P=.040), greater interleukin-1beta responsive to TLR-2 stimulation
      (P=.040), and flatter diurnal cortisol slopes (P=.010), indicating inflammatory
      dysregulation. In IC/BPS patients, inflammation after TLR-4 stimulation was
      associated with multiple symptoms, including genitourinary pain (P=.010), sexual
      pain (P=.002), and marginally with urinary symptoms (P=.068). Genitourinary pain
      severity (P=.008), frequency (P=.001), and pain with intercourse (P=.002) were
      strongly associated with TLR-4 inflammatory response. TLR-4 appears to play a
      central role in painful symptoms of IC/BPS patients, which may be linked to poor
      endogenous inflammatory control. These findings may help to identify new
      mechanisms in IC/BPS and lead to new therapeutic approaches. 

PMID- 24907407
TI  - Extracellular polymeric substances of bacteria and their potential environmental
      applications.
AB  - Biopolymers are considered a potential alternative to conventional chemical
      polymers because of their ease of biodegradability, high efficiency, non-toxicity
      and non-secondary pollution. Recently, extracellular polymeric substances (EPS,
      biopolymers produced by the microorganisms) have been recognised by many
      researchers as a potential flocculent for their applications in various water,
      wastewater and sludge treatment processes. In this context, literature
      information on EPS is widely dispersed and is very scarce. Thus, this review
      marginalizes various studies conducted so far about EPS nature-production
      recovery, properties, environmental applications and moreover, critically
      examines future research needs and advanced application prospective of the EPS.
      One of the most important aspect of chemical composition and structural details
      of different moieties of EPS in terms of carbohydrates, proteins, extracellular
      DNA, lipid and surfactants and humic substances are described. These chemical
      characteristics of EPS in relation to formation and properties of microbial
      aggregates as well as degradation of EPS in the matrix (biomass, flocs etc) are
      analyzed. The important engineering properties (based on structural
      characteristics) such as adsorption, biodegradability,
      hydrophilicity/hydrophobicity of EPS matrix are also discussed in details.
      Different aspects of EPS production process such as bacterial strain maintenance;
      inoculum and factors affecting EPS production were presented. The important
      factors affecting EPS production include growth phase, carbon and nitrogen
      sources and their ratio, role of other nutrients (phosphorus,
      micronutrients/trace elements, and vitamins), impact of pH, temperature, metals,
      aerobic versus anaerobic conditions and pure and mixed culture. The production of
      EPS in high concentration with high productivity is essential due to economic
      reasons. Therefore, the knowledge about all the aspects of EPS production (listed
      above) is highly essential to formulate a logical and scientific basis for the
      research and industrial activities. One of the very important issues in the
      production/application/biodegradation of EPS is how the EPS is extracted from the
      matrix or a culture broth. Moreover, EPS matrix available in different forms
      (crude, loosely bound, tightly bound, slime, capsular and purified) can be used
      as a bioflocculant material. Several chemical and physical methods for the
      extraction of EPS (crude form or purified form) from different sources have been
      analyzed and reported. There is ample information available in the literature
      about various EPS extraction methods. Flocculability, dewaterability and
      biosorption ability are the very attractive engineering properties of the EPS
      matrix. Recent information on important aspects of these properties qualitatively
      as well as quantitatively has been described. Recent information on the mechanism
      of flocculation mediated by EPS is presented. Potential role of EPS in sludge
      dewatering and biosorption phenomenon has been discussed in details. Different
      factors influencing the EPS ability to flocculate and dewaterability of different
      suspensions have been included. The factors considered for the discussion are
      cations, different forms of EPS, concentration of EPS, protein and carbohydrate
      content of EPS, molecular weight of EPS, pH of the suspension, temperature etc.
      These factors were selected for the study based upon their role in the
      flocculation and dewatering mechanism as well the most recent available
      literature findings on these factors. For example, only recently it has been
      demonstrated that there is an optimum EPS concentration for sludge
      flocculation/dewatering. High or low concentration of EPS can lead to
      destabilization of flocs. Role of EPS in environmental applications such as water
      treatment, wastewater flocculation and settling, colour removal from wastewater,
      sludge dewatering, metal removal and recovery, removal of toxic organic
      compounds, landfill leachate treatment, soil remediation and reclamation has been
      presented based on the most recent available information. However, data available
      on environmental application of EPS are very limited. Investigations are required
      for exploring the potential of field applications of EPS. Finally, the
      limitations in the knowledge gap are outlined and the research needs as well as
      future perspectives are highlighted. 

PMID- 24907408
TI  - Expression, purification and reconstitution of the 4-hydroxybenzoate transporter
      PcaK from Acinetobacter sp. ADP1.
AB  - The aromatic acid:H(+) symporter family of integral membrane proteins play an
      important role in the microbial metabolism of aromatic compounds. Here, we show
      that the 4-hydroxybenzoate transporter from Acinetobacter sp. ADP1, PcaK, can be
      successfully overexpressed in Escherichia coli and purified by affinity
      chromatography. Affinity-purified PcaK is a stable, monodisperse homotrimer in
      the detergent n-dodecyl-beta-d-maltopyranoside supplemented with cholesteryl
      hemisuccinate. The purified protein has alpha-helical secondary structure and can
      be reconstituted to a functional state in synthetic proteoliposomes. Asymmetric
      substrate transport was observed when proteoliposomes were energized by applying
      an electrochemical proton gradient (DeltaMU?H(+)) or a membrane potential
      (DeltaPsi) but not by DeltapH alone. PcaK was selective in transporting 4
      hydroxybenzoate and 3,4-dihydroxybenzoate over closely related compounds,
      confirming previous reports on substrate specificity. However, PcaK also showed
      an unexpected preference for transporting 2-hydroxybenzoates. These results
      provide the basis for further detailed studies of the structure and function of
      this family of transporters.

PMID- 24907409
TI  - Secretion of recombinant archeal lipase mediated by SVP2 signal peptide in
      Escherichia coli and its optimization by response surface methodology.
AB  - Towards the targeting of recombinant Thermoanaerobacter thermohydrosulfuricus
      lipase (TtL) for secretion into the culture medium of Escherichia coli, we have
      investigated a combination of the archeal lipase gene with a Salinovibrio
      metalloprotease (SVP2) signal peptide sequence. The SVP2 signal peptide has shown
      all necessary features of a leader sequence for high level secretion of a
      recombinant target protein in E. coli. Two sets of primers were designed for
      amplification of the corresponding gene fragments by PCR. Firstly, the PCR
      product of the TtL gene with designed restriction sites of SacI and HindIII was
      cloned into pQE-80L plasmid, named as pQE80L-TtL. Afterwards, the amplified
      fragment of SVP2 signal peptide with EcoRI and SacI restriction sites was also
      cloned into pQE80L-TtL and the final construct pQE-STL was obtained. A study on
      the extracellular expression of recombinant STL revealed that most of the enzyme
      activity was located in the periplasmic space. Glycine and Triton X-100 were
      investigated to determine whether the leakage of recombinant STL from the outer
      membrane was promoted, and it was revealed that glycine has a positive effect.
      Statistical media optimization design was then applied to optimize the effect of
      seven factors including glycine, Triton X-100, IPTG, yeast extract concentration,
      incubation time, induction time, and temperature on the extracellular expression
      of STL. The optimum conditions for the secretion of the lipase was obtained by
      incubating recombinant E. coli BL21 cells in the medium supplemented by 1.27%
      glycine and 24h of incubation in the presence of 0.2mM IPTG concentration. 

PMID- 24907410
TI  - Reducing Recon 2 for steady-state flux analysis of HEK cell culture.
AB  - A representative stoichiometric model is essential to perform metabolic flux
      analysis (MFA) using experimentally measured consumption (or production) rates as
      constraints. For Human Embryonic Kidney (HEK) cell culture, there is the
      opportunity to use an extremely well-curated and annotated human genome-scale
      model Recon 2 for MFA. Performing MFA using Recon 2 without any modification
      would have implied that cells have access to all functionality encoded by the
      genome, which is not realistic. The majority of intracellular fluxes are poorly
      determined as only extracellular exchange rates are measured. This is compounded
      by the fact that there is no suitable metabolic objective function to suppress
      non-specific fluxes. We devised a heuristic to systematically reduce Recon 2 to
      emphasize flux through core metabolic reactions. This implies that cells would
      engage these dominant metabolic pathways to grow, and any significant changes in
      gross metabolic phenotypes would have invoked changes in these pathways. The
      reduced metabolic model becomes a functionalized version of Recon 2 used for
      identifying significant metabolic changes in cells by flux analysis. 

PMID- 24907412
TI  - Role of miRNAs in bone and their potential as therapeutic targets.
AB  - MicroRNAs (miRNAs) are noncoding, single-stranded RNAs that regulate the
      expression of target genes by binding their 3'-untranslated region. miRNAs are
      important regulators of various biological processes, including cellular
      differentiation, proliferation, apoptosis, and tissue development. Furthermore,
      aberrant miRNA expression has emerged as an important pathomechanism in various
      human diseases, including osteoporosis. Thus, the therapeutic potential of miRNA
      has attracted great interest recently. Here, we focused on the roles of miRNAs in
      bone homeostasis and the potential of miRNAs as therapeutic targets. 

PMID- 24907411
TI  - Humoral immunity induced by mucosal and/or systemic SIV-specific vaccine
      platforms suggests novel combinatorial approaches for enhancing responses.
AB  - Combinatorial HIV/SIV vaccine approaches targeting multiple arms of the immune
      system might improve protective efficacy. We compared SIV-specific humoral
      immunity induced in rhesus macaques by five vaccine regimens. Systemic regimens
      included ALVAC-SIVenv priming and Env boosting (ALVAC/Env); DNA immunization; and
      DNA plus Env co-immunization (DNA&Env). RepAd/Env combined mucosal replication
      competent Ad-env priming with systemic Env boosting. A Peptide/Env regimen, given
      solely intrarectally, included HIV/SIV peptides followed by MVA-env and Env
      boosts. Serum antibodies mediating neutralizing, phagocytic and ADCC activities
      were induced by ALVAC/Env, RepAd/Env and DNA&Env vaccines. Memory B cells and
      plasma cells were maintained in the bone marrow. RepAd/Env vaccination induced
      early SIV-specific IgA in rectal secretions before Env boosting, although mucosal
      IgA and IgG responses were readily detected at necropsy in ALVAC/Env, RepAd/Env,
      DNA&Env and DNA vaccinated animals. Our results suggest that combined RepAd
      priming with ALVAC/Env or DNA&Env regimen boosting might induce potent,
      functional, long-lasting systemic and mucosal SIV-specific antibodies. 

PMID- 24907414
TI  - Revealing pathway maps of renal cell carcinoma by gene expression change.
AB  - Protein-protein interactions (PPIs) and gene expression profiles interact with
      each other in the regulation of a pathway. Many studies have expressed the
      feasibility of deriving the pathway from the PPI network or gene expression
      information. However, previous researches are still limited to a small region of
      large-scale genomics and whole-proteomics. Furthermore, the gene information
      induced by diseases had not been considered yet in such researches. In this
      study, we propose an approach to find potential fragments of active pathways
      related to various stages of diseases by a top-rank score-based method,
      integrating PPI network and gene expression change information. Validation of
      produced pathway maps is performed by mapping with KEGG renal cell carcinoma
      (RCC) map. The pathway maps of RCC are built and three key genes are found. The
      accuracies of coverage ratio of the produced pathway map are 50% and 48.48%. In
      this case, the hubs that link the nodes from RCC provide a valuable guide for
      further studies for understanding RCC. In conclusion, the pathway map co
      constructed by this proposed method can provide more insight than limited
      subnetwork biomarkers. 

PMID- 24907413
TI  - Role for beta-arrestin in mediating paradoxical beta2AR and PAR2 signaling in
      asthma.
AB  - G protein-coupled receptors (GPCRs) utilize (at least) two signal transduction
      pathways to elicit cellular responses including the classic G protein-dependent,
      and the more recently discovered beta-arrestin-dependent, signaling pathways. In
      human and murine models of asthma, agonist-activation of beta2-adrenergic
      receptor (beta2AR) or Protease-activated-receptor-2 (PAR2) results in relief from
      bronchospasm via airway smooth muscle relaxation. However, chronic activation of
      these receptors, leads to pro-inflammatory responses. One plausible explanation
      underlying the paradoxical effects of beta2AR and PAR2 agonism in asthma is that
      the beneficial and harmful effects are associated with distinct signaling
      pathways. Specifically, G protein-dependent signaling mediates relaxation of
      airway smooth muscle, whereas beta-arrestin-dependent signaling promotes
      inflammation. This review explores the evidence supporting the hypothesis that
      beta-arrestin-dependent signaling downstream of beta2AR and PAR2 is detrimental
      in asthma and examines the therapeutic opportunities for selectively targeting
      this pathway. 

PMID- 24907415
TI  - A prediction model of drug-induced ototoxicity developed by an optimal support
      vector machine (SVM) method.
AB  - Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to
      be considered in drug discovery. Nevertheless, current experimental methods used
      to evaluate drug-induced ototoxicity are often time-consuming and expensive,
      indicating that they are not suitable for a large-scale evaluation of drug
      induced ototoxicity in the early stage of drug discovery. We thus, in this
      investigation, established an effective computational prediction model of drug
      induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG
      SVM. Three GA-CG-SVM models were developed based on three training sets
      containing agents bearing different risk levels of drug-induced ototoxicity. For
      comparison, models based on naive Bayesian (NB) and recursive partitioning (RP)
      methods were also used on the same training sets. Among all the prediction
      models, the GA-CG-SVM model II showed the best performance, which offered
      prediction accuracies of 85.33% and 83.05% for two independent test sets,
      respectively. Overall, the good performance of the GA-CG-SVM model II indicates
      that it could be used for the prediction of drug-induced ototoxicity in the early
      stage of drug discovery. 

PMID- 24907416
TI  - Modeling and simulation of speed selection on left ventricular assist devices.
AB  - The control problem for LVADs is to set pump speed such that cardiac output and
      pressure perfusion are within acceptable physiological ranges. However, current
      technology of LVADs cannot provide for a closed-loop control scheme that can make
      adjustments based on the patient's level of activity. In this context, the
      SensorART Speed Selection Module (SSM) integrates various hardware and software
      components in order to improve the quality of the patients' treatment and the
      workflow of the specialists. It enables specialists to better understand the
      patient-device interactions, and improve their knowledge. The SensorART SSM
      includes two tools of the Specialist Decision Support System (SDSS); namely the
      Suction Detection Tool and the Speed Selection Tool. A VAD Heart Simulation
      Platform (VHSP) is also part of the system. The VHSP enables specialists to
      simulate the behavior of a patient's circulatory system, using different LVAD
      types and functional parameters. The SDSS is a web-based application that offers
      specialists with a plethora of tools for monitoring, designing the best therapy
      plan, analyzing data, extracting new knowledge and making informative decisions.
      In this paper, two of these tools, the Suction Detection Tool and Speed Selection
      Tool are presented. The former allows the analysis of the simulations sessions
      from the VHSP and the identification of issues related to suction phenomenon with
      high accuracy 93%. The latter provides the specialists with a powerful support in
      their attempt to effectively plan the treatment strategy. It allows them to draw
      conclusions about the most appropriate pump speed settings. Preliminary
      assessments connecting the Suction Detection Tool to the VHSP are presented in
      this paper. 

PMID- 24907418
TI  - The expansion of body coloration involves coordinated evolution in cis and trans
      within the pigmentation regulatory network of Drosophila prostipennis.
AB  - The generation of complex morphological features requires the precisely
      orchestrated expression of numerous genes during development. While several
      traits have been resolved to evolutionary changes within a single gene, the
      evolutionary path by which genes derive co-localized or mutually excluded
      expression patterns is currently a mystery. Here we investigate how the
      Drosophila pigmentation gene network was altered in Drosophila prostipennis, a
      species in the Drosophila melanogaster subgroup, that evolved expanded abdominal
      pigmentation. We show that this expansion involved broadened expression of the
      melanin-promoting enzyme genes tan and yellow, and a reciprocal withdrawn pattern
      of the melanin-suppressing enzyme gene ebony. To examine whether these
      coordinated changes to the network were generated through mutations in the cis
      regulatory elements (CREs) of these genes, we cloned and tested CREs of D.
      prostipennis tan, ebony, and yellow in transgenic reporter assays. Regulatory
      regions of both tan and ebony failed to recapitulate the derived D. prostipennis
      expression phenotype, implicating the modification of a factor or factors
      upstream of both genes. However, the D. prostipennis yellow cis-regulatory region
      recapitulated the expanded expression pattern observed in this species,
      implicating causative mutations in cis to yellow. Our results provide an example
      in which a coordinated expression program evolved through independent changes at
      multiple loci, rather than through changes to a single "master regulator"
      directing a suite of downstream target genes. This implies a complex network
      structure in which each gene may be subject to a unique set of inputs, and
      resultantly may require individualized evolutionary paths to yield correlated
      gene expression patterns. 

PMID- 24907419
TI  - Should neuroecologists separate Tinbergen's four questions?
AB  - Neuroecologists have been criticized for deriving mechanistic explanations about
      brains and cognition from functional results. Historically, it appears however
      that the first functional predictions about adaptive hippocampal specialization
      for spatial memory of stored food were preceded, not followed, by the mechanistic
      paradigm of massive modularity that was dominant in the 1990s. More attention is
      paid nowadays to domain general aspects of cognition and to neural connectivity.
      Attention is also now given to evo devo principles of brain organization, which
      suggest conserved routes to evolutionary changes in the brain driven by conserved
      developmental schedules. Knowledge gained in answering each of Tinbergen's four
      questions is thus useful in making predictions concerning the other ones. This
      article is part of a Special Issue entitled: In Honor of Jerry Hogan.

PMID- 24907417
TI  - Direct functional consequences of ZRS enhancer mutation combine with secondary
      long range SHH signalling effects to cause preaxial polydactyly.
AB  - Sonic hedgehog (SHH) plays a central role in patterning numerous embryonic
      tissues including, classically, the developing limb bud where it controls digit
      number and identity. This study utilises the polydactylous Silkie (Slk) chicken
      breed, which carries a mutation in the long range limb-specific regulatory
      element of SHH, the ZRS. Using allele specific SHH expression analysis combined
      with quantitative protein analysis, we measure allele specific changes in SHH
      mRNA and concentration of SHH protein over time. This confirms that the Slk ZRS
      enhancer mutation causes increased SHH expression in the posterior leg
      mesenchyme. Secondary consequences of this increased SHH signalling include
      increased FGF pathway signalling and growth as predicted by the SHH/GREM1/FGF
      feedback loop and the Growth/Morphogen models. Manipulation of Hedgehog, FGF
      signalling and growth demonstrate that anterior-ectopic expression of SHH and
      induction of preaxial polydactyly is induced secondary to increased SHH
      signalling and Hedgehog-dependent growth directed from the posterior limb. We
      predict that increased long range SHH signalling acts in combination with changes
      in activation of SHH transcription from the Slk ZRS allele. Through analysis of
      the temporal dynamics of anterior SHH induction we predict a gene regulatory
      network which may contribute to activation of anterior SHH expression from the
      Slk ZRS. 

PMID- 24907420
TI  - Pringle manoeuvre versus selective hepatic vascular exclusion in partial
      hepatectomy for tumours adjacent to the hepatocaval junction: a randomized
      comparative study.
AB  - OBJECTIVE: To compare the efficacy of selective hepatic vascular exclusion versus
      Pringle manoeuvre in partial hepatectomy for tumours adjacent to the hepatocaval
      junction. METHODS: A randomized comparative trial was carried out. The primary
      endpoint was intraoperative blood loss. The secondary endpoints were operation
      time, blood transfusion, postoperative liver function recovery, procedure-related
      morbidity and in-hospital mortality. RESULTS: 160 patients were randomized into 2
      groups: the Pringle manoeuvre group (n = 80) and the selective hepatic vascular
      exclusion (SHVE) group (n = 80). Intraoperative blood loss and transfusion
      requirements were significantly less in the SHVE group. In the SHVE group,
      laceration of hepatic veins happened in 18 patients. Profuse intraoperative blood
      loss of over 2 L happened in 2 patients but no patient suffered from air embolism
      because the hepatic veins were controlled. In the Pringle group, the hepatic
      veins were lacerated in 20 patients, with profuse blood loss of over 2 L in 7
      patients and air embolism in 3 patients. The rates of postoperative bleeding,
      reoperation, liver failure and mortality were significantly higher and the ICU
      stay and hospital stay were significantly longer in the Pringle group.
      CONCLUSIONS: SHVE was more efficacious than Pringle manoeuvre for partial
      hepatectomy in patients with tumours adjacent to the hepatocaval junction.

PMID- 24907421
TI  - Augmented miR-150 expression associated with depressed SOCS1 expression involved
      in dengue haemorrhagic fever.
AB  - OBJECTIVE: Suppressors of cytokine signalling (SOCS) proteins regulate cytokine
      responses and control immune balance. The objective of our study was to determine
      whether the expression of SOCS1 and its potential regulatory microRNAs (miRNAs)
      in leukocytes is correlated to the development of dengue haemorrhagic fever
      (DHF). METHODS: We performed a case-control study to investigate the SOCS1 and
      miRNA expression in leukocytes for patients with DF and DHF in a DENV-2 outbreak
      that occurred in Taiwan between 2002 and 2003. We performed reverse transcription
      polymerase chain reaction to evaluate the expression of SOCS1 and its regulatory
      miRNAs in mononuclear leukocytes obtained from patients with or without DHF. The
      reciprocal relationship between SOCS1 and miR-150 expression was validated in
      DENV-2-infected peripheral mononuclear cells (PBMCs). RESULTS: SOCS1 expression
      and lower IFN-gamma level were significantly reduced in DHF patients, but not in
      patients with DF. Elevated SOCS1 and reduced miR-150 levels were detected 24 h
      after DENV-2 infection in PBMCs. Transfection of a miR-150 mimic into CD14(+)
      cells infected with DENV-2 suppressed the induction of SOCS1 expression in a dose
      dependent manner. CONCLUSION: We demonstrate for the first time that augmented
      miR-150 expression with depressed SOCS1 expression in CD14(+) cells are
      associated with the pathogenesis of DHF.

PMID- 24907422
TI  - Induced antiviral innate immunity in Drosophila.
AB  - Immunity to viral infections in the model organism Drosophila melanogaster
      involves both RNA interference and additional induced responses. The latter
      include not only cellular mechanisms such as programmed cell death and autophagy,
      but also the induction of a large set of genes, some of which contribute to the
      control of viral replication and resistance to infection. This induced response
      to infection is complex and involves both virus-specific and cell-type specific
      mechanisms. We review here recent developments, from the sensing of viral
      infection to the induction of signaling pathways and production of antiviral
      effector molecules. Our current understanding, although still partial, validates
      the Drosophila model of antiviral induced immunity for insect pests and disease
      vectors, as well as for mammals. 

PMID- 24907423
TI  - Cholinergic immunotoxin 192 IgG-SAPORIN alters subicular theta-gamma activity and
      impairs spatial learning in rats.
AB  - Subiculum is an important structure of hippocampal formation and is a part of
      intra hippocampal network involved in spatial information processing. However,
      relatively very few studies are available in literature demonstrating the
      explicit role of subiculum in spatial information processing. The present study
      investigated the cholinergic modulation of subicular theta-gamma activity on
      spatial learning and memory functions in rats. The cholinergic projections to
      ventral subiculum were selectively eliminated using 192 IgG-SAPORIN. Eliminations
      of cholinergic inputs to ventral subiculum significantly reduced the subicular
      theta and enhanced the gamma activity during active wake and REM sleep states. In
      addition, the spatial learning was severely impaired following cholinergic
      elimination of ventral subiculum. The ChAT immunocytochemical studies showed
      sparse distribution of cholinergic fibers in the ventral subiculum confirming the
      cholinergic elimination to ventral subiculum. Cholinotoxic infusions to ventral
      subiculum did not alter the hippocampal cholinergic innervations and retained the
      hippocampal theta and gamma activities. The present findings support that
      cholinergic modulation of subicular theta-gamma oscillations is crucial for
      spatial information processing. 

PMID- 24907424
TI  - No effect of remote ischaemic conditioning on inflammation in a porcine kidney
      transplantation model.
AB  - MAIN PROBLEM: Delayed graft function after kidney transplantation is associated
      with decreased graft survival and increased patient mortality but the
      pathogenesis is poorly understood. Remote ischaemic conditioning (rIC) may
      prevent delayed graft function by an anti-inflammatory effect. In a porcine model
      of transplantation from adults to children, we investigated the inflammatory
      response in the transplanted kidney and the effect of rIC. METHODS: Kidneys were
      recovered from brain dead donor pigs(63kg) and transplanted into two groups of
      recipient pigs(15kg) after 22h of cold ischaemia. Recipients were randomised to
      either: rIC (n=8) performed before the 10-h reperfusion period or no-rIC (n=8).
      Non-transplanted kidneys from eight brain dead pigs served as controls. RESULTS:
      Compared to controls, transplantation increased the number of apoptotic cells,
      macrophages and neutrophils in the kidney. After transplantation, IL-10 levels
      increased and IL-6 levels decreased in the kidney, whereas levels of TNF-alpha
      and IL-8 were not affected. A significant rise in plasma IL-1beta and IL-6 was
      observed in the recipients after transplantation. Plasma IL-10 was not affected
      by transplantation and TNF-alpha and IL-8 were below detection limit. No effect
      of rIC was found with regards to cell infiltration or cytokine production.
      CONCLUSION: Renal transplantation elicits an inflammatory response in the kidney
      manifested as apoptotic cell death, macrophage and neutrophil infiltration, and
      an anti-inflammatory cytokine response 10h after transplantation. This response
      was not modified by rIC.

PMID- 24907425
TI  - Frequency of regulatory T-cell and hepatitis C viral antigen-specific immune
      response in recurrent hepatitis C after liver transplantation.
AB  - INTRODUCTION: Regulatory T (Treg) and type 1 regulatory T (Tr1) cells facilitate
      hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT).
      However, their frequencies and effects on HCV-specific immune responses have not
      been well investigated. METHODS: We determined Treg and Tr1 frequencies in OLT
      patients with hepatitis C and assessed their associations with HCV-specific T
      cell responses. These patients comprised the following groups: an early post
      transplantation group (n=14); an OLT-chronic active hepatitis C group (n=14) with
      active hepatitis C (alanine aminotransferase of>upper limit of normal/positive
      for HCV-RNA); an OLT-persistently normal alanine aminotransferase group (n=12)
      without active hepatitis C (not interferon/positive for HCV-RNA); and an OLT
      sustained viral response group (n=6) with sustained viral responses using
      interferon treatment (negative for HCV-RNA). The frequencies of HCV-specific CD4+
      T cells that secreted interferon-gamma were determined by enzyme-linked
      immunosorbent spot assay (except for the OLT early group). RESULTS: Treg and Tr1
      frequencies were low during the early post-transplantation period. OLT patients
      with sustained viral responses had lower Treg frequencies than those with chronic
      hepatitis C, whereas Tr1 frequencies were significantly reduced in OLT patients
      with persistently normal alanine aminotransferase levels compared to those with
      chronic hepatitis C (p<0.05). Treg frequencies positively correlated with HCV NS3
      antigen-specific interferon-gamma responses, which corresponded to HCV clearance.
      CONCLUSIONS: Increased Treg frequencies and reduced HCV-NS3 antigen-specific
      responses recovered after viral eradication in post-OLT chronic hepatitis C
      patients. Reduced Tr1 frequencies were associated with hepatitis activity
      control, which may facilitate controlling chronic hepatitis C in patients after
      OLT.

PMID- 24907428
TI  - Pushing to a cure by harnessing innate immunity against hepatitis C virus.
AB  - Hepatitis C virus (HCV) causes 350,000 deaths and infects at least 3million
      people worldwide every year. Currently no vaccine has been developed. Direct
      acting antiviral (DAA) drugs with high efficacy for suppressing HCV infection
      have recently been introduced into the clinic. While DAAs initially required
      combination therapy with type-1 interferon (IFN) administration for full efficacy
      and to avoid viral resistance to treatment, new DAA combinations show promise as
      an IFN-free regimen. However, IFN-free DAA therapy is in its infancy, still to be
      proven and today is cost-prohibitive for the patient. A major goal in HCV therapy
      to remove or replace IFN with DAAs or an alternative therapeutic to render
      virologic response with continued virus sensitivity to DAAs, thus facilitating a
      cure for infection. Recent advances in our understanding of innate immune
      responses to HCV have identified new therapeutic targets to combat HCV infection.
      We discuss how the targeting of innate immune response factors can be harnessed
      with DAAs to produce new generations of DAA-based HCV therapeutics. This article
      forms part of a symposium in Antiviral Research on "Hepatitis C: next steps
      toward global eradication." 

PMID- 24907427
TI  - Inhibition of adenovirus replication by a trisubstituted piperazin-2-one
      derivative.
AB  - The number of disseminated adenovirus (Ad) infections continues to increase
      mostly due to the growing use of immunosuppressive treatments. Recipients of
      solid organ or hematopoietic stem cell transplants, mainly in pediatric units,
      exhibit a high morbidity and mortality due to these infections. Unfortunately,
      there are no Ad-specific antiviral drugs currently approved for medical use. To
      address this situation, we used high-throughput screening (HTS) of synthetic
      small molecule libraries to identify compounds that restrict Ad infection. Among
      the more than 25,000 compounds screened, we identified a hit compound that
      significantly inhibited Ad infection. The compound (15D8) is a trisubstituted
      piperazin-2-one derivative that showed substantial antiviral activity with little
      or no cytotoxicity at low micromolar concentrations. Compound 15D8 selectively
      inhibits Ad DNA replication in the nucleus, providing a potential candidate for
      the development of a new class of antiviral compounds to treat Ad infections. 

PMID- 24907429
TI  - Soma, food of the immortals according to the Bower Manuscript (Kashmir, 6th
      century A.D.).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Food is medicine and vice versa. In Hindu and
      Ayurvedic medicine, and among human cultures of the Indian subcontinent in
      general, the perception of the food-medicine continuum is especially well
      established. The preparation of the exhilarating, gold-coloured Soma, Amrita or
      Ambrosia, the elixir and food of the 'immortals'-the Hindu pantheon-by the
      ancient Indo-Aryans, is described in the Rigveda in poetic hymns. Different
      theories regarding the botanical identity of Soma circulate, but no
      pharmacologically and historically convincing theory exists to date. We intend to
      contribute to the botanical, chemical and pharmacological characterisation of
      Soma through an analysis of two historical Amrita recipes recorded in the Bower
      Manuscript. The recipes are referred therein as panaceas (clarified butter) and
      also as a medicine to treat nervous diseases (oil), while no exhilarating
      properties are mentioned. Notwithstanding this, we hypothesise, that these
      recipes are related to the ca. 1800 years older Rigvedic Soma. We suppose that
      the psychoactive Soma ingredient(s) are among the components, possibly in smaller
      proportions, of the Amrita recipes preserved in the Bower Manuscript. MATERIALS
      AND METHODS: The Bower Manuscript is a medical treatise recorded in the 6th
      century A.D. in Sanskrit on birch bark leaves, probably by Buddhist monks, and
      unearthed towards the end of the 19th century in Chinese Turkestan. We analysed
      two Amrita recipes from the Bower Manuscript, which was translated by Rudolf
      Hoernle into English during the early 20th century. A database search with the
      updated Latin binomials of the herbal ingredients was used to gather quantitative
      phytochemical and pharmacological information. RESULTS: Together, both Amrita
      recipes contain around 100 herbal ingredients. Psychoactive alkaloid containing
      species still important in Ayurvedic, Chinese and Thai medicine and mentioned in
      the recipe for 'Amrita-Prasa clarified butter' and 'Amrita Oil' are: Tinospora
      cordifolia (Amrita, Guduchi), three Sida spp., Mucuna pruriens, Nelumbo nucifera,
      Desmodium gangeticum, and Tabernaemontana divaricata. These species contain
      several notorious and potential psychoactive and psychedelic alkaloids, namely:
      tryptamines, 2-phenylethylamine, ephedrine, aporphines, ibogaine, and L-DOPA.
      Furthermore, protoberberine alkaloids, tetrahydro-beta-carbolines, and
      tetrahydroisoquinolines with monoamine oxidase inhibitor (MAO-I) activity but
      also neurotoxic properties are reported. CONCLUSIONS: We propose that Soma was a
      combination of a protoberberine alkaloids containing Tinospora cordifolia juice
      with MAO-I properties mixed together with a tryptamine rich Desmodium gangeticum
      extract or a blending of Tinospora cordifolia with an ephedrine and
      phenylethylamine-rich Sida spp. extract. Tinospora cordifolia combined with
      Desmodium gangeticum might provide a psychedelic experience with visual effects,
      while a combination of Tinospora cordifolia with Sida spp. might lead to more
      euphoric and amphetamine-like experiences.

PMID- 24907426
TI  - siRNA delivery to the lung: what's new?
AB  - RNA interference (RNAi) has been thought of as the general answer to many unmet
      medical needs. After the first success stories, it soon became obvious that short
      interfering RNA (siRNA) is not suitable for systemic administration due to its
      poor pharmacokinetics. Therefore local administration routes have been adopted
      for more successful in vivo RNAi. This paper reviews nucleic acid modifications,
      nanocarrier chemistry, animal models used in successful pulmonary siRNA delivery,
      as well as clinical translation approaches. We summarize what has been published
      recently and conclude with the potential problems that may still hamper the
      efficient clinical application of RNAi in the lung. 

PMID- 24907431
TI  - Choroidal thickness and volume in healthy young white adults and the
      relationships between them and axial length, ammetropy and sex.
AB  - PURPOSE: To evaluate choroidal thickness in young adults using enhanced-depth
      imaging spectral-domain optical coherence tomography and to describe volume
      differences in all the areas defined in the Early Treatment Diabetic Retinopathy
      Study. DESIGN: Prospective clinical study. METHODS: In 95 healthy young (23.8 +/-
      3.2 years) adult volunteers, 95 eyes were prospectively enrolled. Manual
      choroidal segmentation on a 25-raster horizontal scan protocol was performed. The
      measurements of the 9 subfields defined by the Early Treatment Diabetic
      Retinopathy Study were evaluated. RESULTS: Mean subfoveal choroidal thickness was
      345.67 +/- 81.80 MUm and mean total choroidal volume was 8.99 +/- 1.88 mm(3).
      Choroidal thickness and volume were higher in the superior and temporal areas
      than in the inferior and nasal sectors of the same diameter, respectively. Strong
      correlations between subfoveal choroidal thickness and axial length and myopic
      refractive error were obtained (r = -0.649, P < 0.001, and r = 0.473, P < 0.001,
      respectively). Emmetropic eyes tended to have thicker subfoveal choroidal
      thickness (381.94 +/- 79.88 MUm vs 307.04 +/- 64.91 MUm) and higher total
      choroidal volume than myopic eyes (9.80 +/- 1.87 mm(3) vs 8.14 +/- 1.48 mm(3)).
      The estimation of the variation in the subfoveal choroidal thickness in
      relationship to the axial length was -43.84 MUm/mm. In the myopic group, the
      variation in the subfoveal choroidal thickness with the myopic refractive error
      was -10.45 MUm per diopter. CONCLUSIONS: This study establishes for the first
      time a normal database for choroidal thickness and volume in young adults. Axial
      length, and myopic ammetropy are highly associated with choroidal parameters in
      healthy subjects. Enhanced-depth imaging spectral-domain optical coherence
      tomography exhibited a high degree of intraobserver and interobserver
      repeatability.

PMID- 24907430
TI  - Six weeks oral gavage of a Phyllanthus acidus leaf water extract decreased
      visceral fat, the serum lipid profile and liver lipid accumulation in middle-aged
      male rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Advancing age is associated with an increased
      accumulation of visceral fat and liver lipid which is then responsible for an age
      related risk for cardiovascular disease. Looking after ourselves well with
      suitable micronutrients could prevent disease or prolong our healthy
      cardiovascular functions. In Thai traditional medicine, leaves of Phyllanthus
      acidus (PA) have been used for many purposes including as an antihypertensive
      agent and to provide relief from a headache caused by hypertension. We aimed to
      investigate the effects of a chronic oral administration of PA extracts to middle
      aged (12-14 months) rats on their body weight, food intake, body fats, liver and
      kidney functions, fasting blood glucose and lipid profiles, liver lipid
      accumulation and on blood pressure. MATERIALS AND METHODS: Three different kinds
      of PA extracts were used: (1) a PA water extract, (2) a heated PA water extract,
      and (3) an n-butanol fraction of the PA water extract, prepared from fresh leaves
      of Phyllanthus acidus. The rats were orally gavaged with the three PA extracts at
      1.0 g/kg body weight or, as a control, with distilled water once a day for 6
      weeks. Fasting blood sugar, lipid profile and ALP, SGOT, SGPT, BUN and creatinine
      levels were measured by enzymatic methods. Liver lipid accumulation was measured
      using oil red O staining on fresh thin cryostat liver tissue sections. The animal
      basal blood pressure and heart rate were measured in anesthetized rats via a
      common carotid artery using a polygraph. RESULTS: Results showed that after 6
      weeks of treatment using gavaged heated PA extract and PA n-butanol extract there
      were no changes in any of the parameters studied. However, the initial PA water
      extract caused a slight decrease in the animal body weight with no change in food
      intake. No changes were observed in the liver and kidney functions (serum ALP,
      SGOT, SGPT, BUN and creatinine did not change), nor did the fasting blood sugar
      or triglyceride levels differ significantly. Serum cholesterol, HDL and LDL
      levels, as well as visceral and subcutaneous adipose tissue and liver lipid
      accumulation were significantly decreased compared to that of the control group.
      There were no differences found in the basal systolic and diastolic blood
      pressure and the basal heart rate between the PA water extract treatment and the
      control group. CONCLUSIONS: These results indicated that the PA water extract had
      an effect on lipid metabolisms that resulted in a decrease of the serum lipid
      profile, visceral and subcutaneous fat, as well as on liver lipid accumulation in
      middle-aged rats. The active component that is responsible for these effects is
      likely to be a water soluble substance(s) and is heat labile. As a consequence of
      these beneficial effects of the PA water extract, it would be a good choice for
      further development for use as a nutraceutical or health product to prevent
      and/or to slow down the development of obesity and/or cardiovascular disease.

PMID- 24907432
TI  - Early macular retinal ganglion cell loss in dominant optic atrophy: genotype
      phenotype correlation.
AB  - PURPOSE: To assess the peripapillary retinal nerve fiber and macular retinal
      ganglion cell (RGC) loss in patients with dominant optic atrophy (DOA) stratified
      by OPA1 mutation type. DESIGN: Cross-sectional study. METHODS: We studied 39
      patients from 28 pedigrees with DOA harboring heterozygous mutations in the OPA1
      gene along with 45 age-matched healthy subjects. The retinal nerve fiber layer
      (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) of patients with DOA were
      evaluated by optical coherence tomography (OCT) and compared to those of
      controls. Patients' eyes were divided into 4 groups based on increasing severity
      of visual loss (DOA1 to DOA4) and were stratified by OPA1 mutation type. RESULTS:
      The average thicknesses of the RNFL and GC-IPL were smaller in patients with DOA
      than in healthy controls (P < 0.0001). RNFL analysis showed a significant
      reduction of the average, superior and inferior quadrants thicknesses in the DOA4
      group compared to the DOA1 group (P = 0.001, P = 0.002 and P = 0.001,
      respectively). GC-IPL analysis showed a significant thinning in the
      superotemporal and superior sectors in the patients with DOA2 compared to those
      with DOA1 (P = 0.046 and P = 0.04, respectively). Stratifying by mutation type,
      average, superior and nasal RNFL thinning was significantly more severe in
      missense mutations and had a presumed dominant-negative effect compared to
      mutations causing haploinsufficiency. CONCLUSIONS: The present study demonstrates
      that in DOA, loss of macular RGCs is the earliest pathologic event, better
      reflected by GC-IPL measurements, whereas RNFL thickness is a measure of spared
      axons in late stages of the disease. Thus, mild cases (DOA2) show significant
      macular RGC loss as opposed to substantial maintenance of RNFL thickness, which
      is significantly decreased only in severe cases (DOA4). A clear
      genotype/phenotype correlation emerged, stratifying OCT measures by OPA1 mutation
      type, missense mutations being the most severe.

PMID- 24907434
TI  - Visual outcomes in pediatric optic neuritis.
AB  - PURPOSE: To describe the visual outcomes of a large cohort of pediatric patients
      presenting to a tertiary care pediatric hospital with first-episode optic
      neuritis. DESIGN: Retrospective, observational cohort study. METHODS: In a
      tertiary care pediatric hospital, patients with first-episode optic neuritis and
      at least 3 months of follow-up over a 10-year period were assessed and followed
      up in the ophthalmology department. The main outcome measures were visual acuity
      at 3 months and 1 year of follow-up, with analysis of risk factors for poor
      visual outcomes and the time course of visual recovery. RESULTS: Of the 59
      pediatric patients with first-episode optic neuritis, 46 had at least 3 months of
      follow-up and 36 had at least 1 year of follow-up. The mean age was 12.6 years
      old; 72% were female, 41% had bilateral involvement, 52% had or developed an
      underlying diagnosis (39% multiple sclerosis, 7% acute disseminated
      encephalomyelitis, 7% neuromyelitis optica), and 91% received treatment (85%
      steroids, 7% multimodal). At 1 year, 81% were at least 20/20 and 89% were at
      least 20/40. A poor visual outcome at 1 year (<20/40) was associated with vision
      of <20/20 at 3 months (P = 0.041). Other clinical characteristics, including
      visual acuity at presentation, sex, bilateral involvement, optic nerve edema, and
      underlying diagnoses were not significantly associated with poor visual outcomes.
      CONCLUSIONS: In this cohort of pediatric patients with optic neuritis, the
      majority of patients regained normal visual acuity at 1 year, regardless of
      baseline clinical characteristics.

PMID- 24907433
TI  - Photoreceptor perturbation around subretinal drusenoid deposits as revealed by
      adaptive optics scanning laser ophthalmoscopy.
AB  - PURPOSE: To describe the microscopic structure of photoreceptors impacted by
      subretinal drusenoid deposits, also called pseudodrusen, an extracellular lesion
      associated with age-related macular degeneration (AMD), using adaptive optics
      scanning laser ophthalmoscopy (AOSLO). DESIGN: Observational case series.
      METHODS: We recruited 53 patients with AMD and 10 age-similar subjects who had
      normal retinal health. All subjects underwent color fundus photography, infrared
      reflectance, red-free reflectance, autofluorescence, and spectral-domain optical
      coherence tomography (OCT). Subretinal drusenoid deposits were classified by a 3
      stage OCT-based grading system. Lesions and surrounding photoreceptors were
      examined by AOSLO. RESULTS: Subretinal drusenoid deposits were found in 26 eyes
      of 13 patients with AMD and imaged by AOSLO and spectral-domain OCT in 18 eyes (n
      = 342 lesions). Spectral-domain OCT showed subretinal drusenoid deposits as
      highly reflective material accumulated internal to the retinal pigment
      epithelium. AOSLO revealed that photoreceptor reflectivity was qualitatively
      reduced by stage 1 subretinal drusenoid deposits and was greatly reduced by stage
      2. AOSLO presented a distinct structure in stage 3, a hyporeflective annulus
      consisting of deflected, degenerated or absent photoreceptors. A central core
      with a reflectivity superficially resembling photoreceptors is formed by the
      lesion material itself. A hyporeflective gap in the photoreceptor ellipsoid zone
      on either side of this core shown in spectral-domain OCT corresponded to the
      hyporeflective annulus seen by AOSLO. CONCLUSIONS: AOSLO and multimodal imaging
      of subretinal drusenoid deposits indicate solid, space-filling lesions in the
      subretinal space. Associated retinal reflectivity changes are related to lesion
      stages and are consistent with perturbations to photoreceptors, as suggested by
      histology.

PMID- 24907436
TI  - Development of an outpatient protocol for lumbar discectomy: our institutional
      experience.
AB  - BACKGROUND: Traditionally, lumbar discectomy has involved overnight hospital
      admission. Recent literature supports the shift to same-day lumbar discectomy
      because of improved outcomes and better patient satisfaction scores. A successful
      protocol for outpatient lumbar discectomies was proposed and implemented at a
      single institution. The aim of this study is to perform a quantitative and
      qualitative analysis of this institutional model. METHODS: Retrospective clinical
      data were collected for patients who underwent a lumbar discectomy during the
      period 2008-2012. Admission and readmission rates, emergency department (ED)
      visit rates, surgical complications, and differences between neurosurgeons
      specializing in spinal procedures and neurosurgeons not specializing in spinal
      procedures were analyzed before and after implementation of the outpatient
      surgery protocol. RESULTS: Of 1011 cases identified, 643 cases of lumbar
      discectomy were performed before the implementation of the protocol, and 368
      cases were performed after implementation. The admission rate before the start
      date of the outpatient protocol was 96.4% versus 50.3% after implementation.
      After protocol implementation, the most common reasons for admission were
      uncontrolled pain (18.9%), late operative start times (14.1%), comorbidities
      (13%), and intraoperative operating room complications (11.9%). Intraoperative
      complications consisted almost exclusively of dural tears. The 30-day readmission
      rate after protocol initiation was 4.6% (n = 17 of 368) versus 2.3% (n = 15 of
      643) before initiation (P = 0.046), and ED visit rate not requiring an admission
      was 2.2% (n = 8 of 368) versus 1.1% (n = 7 of 643) before initiation (P = 0.170).
      CONCLUSIONS: Our data demonstrate that a collaborative protocol for outpatient
      discectomy can be implemented in a safe and effective manner despite a
      statistical increase in hospital readmissions. The percentage rates of
      readmissions and ED visits accounted for a very small percentage of the overall
      number of cases after protocol implementation. Improvements in perioperative pain
      management and ensuring that outpatient lumbar discectomies are scheduled early
      in the day may further decrease the number of admissions. Future studies should
      examine the societal and financial impact of same-day discectomy versus overnight
      hospital stays.

PMID- 24907435
TI  - Treatment of exudative age-related macular degeneration with a designed ankyrin
      repeat protein that binds vascular endothelial growth factor: a phase I/II study.
AB  - PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses
      of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high
      affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive
      patients with exudative age-related macular degeneration (AMD). DESIGN: Phase
      I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to
      receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to
      3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and
      dose response. RESULTS: Altogether, 32 patients received a single injection of
      MP0112. The maximum tolerated dose was 1.0 mg because of a case of
      endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported
      by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7
      mild, 4 moderate in severity). Visual acuity scores were stable or improved
      compared with baseline for >=4 weeks following injection; both retinal thickness
      and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue
      therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg
      MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of
      patients in the higher-dose cohorts who did not require rescue treatment, 83%
      (5/6) maintained reductions in central retinal thickness through week 16.
      CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean
      decreases in retinal thickness and leakage area despite ocular inflammation.
      Larger-scale studies are warranted to confirm these observations.

PMID- 24907437
TI  - Surgical versus nonsurgical treatment of subaxial cervical pedicle fractures.
AB  - BACKGROUND: Pedicle fractures in the cervical spine are common. They may occur in
      isolation or in combination with other concomitant fractures. Multiple
      classification systems have been introduced to provide a clinical framework when
      approaching these types of fractures; however, these systems do not provide
      guidelines for optimal treatment. Data regarding decision making are limited.
      Conservative treatment with orthoses may result in subluxation and instability
      requiring further treatment. Surgery may not be required in all instances because
      many of these injuries may heal without surgical intervention. METHODS: All cases
      of cervical fractures treated at a single institution over a 5-year period were
      retrospectively reviewed. Cases with pedicle fractures were further evaluated,
      and 40 cases managed either with or without surgery were identified. Data on
      presenting history, neurologic examination, imaging findings, comorbidity, method
      of treatment, complication rate, and length of hospital stay were collected.
      Fractures were classified based on computed tomography scans. Data on associated
      injuries were also collected. Fusion rate and fracture displacement were assessed
      by plain radiographs and computed tomography scans at follow-up. Follow-up time
      points included 2, 6, and 12 weeks and 6 months after injury. Primary outcome was
      fracture healing regardless of modality in the absence of progressive deformity
      (i.e., listhesis, kyphosis) and need for further surgery. RESULTS: Conservative
      therapy was administered to 26 patients, and 14 patients underwent surgery. There
      were no statistically significant differences between the 2 groups in terms of
      total levels injured (P = 0.9) or injury severity score (P = 0.5). Patients who
      presented with intact neurologic status were more likely to be treated
      conservatively (88% vs. 29%; P = 0.0004), whereas patients presenting with spinal
      cord injuries were more likely to undergo surgical fixation (35% vs. 0%; P =
      0.0004). Length of hospital stay trended toward being significantly greater in
      patients who underwent surgery (10.6 days vs. 5.5 days; P = 0.07). According to
      our classification system, the most common fracture type was single line
      horizontal fracture occurring in 68% (27 of 40 cases). Vertical split pedicle
      fracture occurred in 28% (11 of 40 cases), and double line horizontal fracture
      occurred in 5% (2 of 40 cases). Posttreatment progressive listhesis was
      significantly higher in patients who were treated conservatively (31% vs. 0%; P =
      0.03), especially when associated with comminuted lateral mass or subluxation or
      both. CONCLUSIONS: This study describes and classifies unique cervical pedicle
      fractures and associated injuries. Our findings suggest that surgical treatment
      results in definitive stability for these injuries compared with conservative
      therapy, particularly for pedicle fractures associated with comminuted lateral
      mass or initially displaced fractures. However, nondisplaced vertical split
      pedicle fractures and isolated single line horizontal fractures may be treated
      nonsurgically without occurrence of further instability. A larger prospective
      study is required to confirm these findings.

PMID- 24907438
TI  - Fully endoscopic interlaminar and transforaminal lumbar discectomy: short-term
      clinical results of 163 surgically treated patients.
AB  - OBJECTIVE: To evaluate the clinical outcomes of patients with lumbar disc disease
      undergoing fully endoscopic surgery at a single clinic. METHODS: Between August
      2009 and January 2012, 163 patients (74 men and 89 women) underwent fully
      endoscopic lumbar discectomy. All patients were followed for 1 year after
      surgery. The Oswestry Disability Index and a visual analog scale were used to
      analyze outcomes. RESULTS: During the follow-up period, 114 (70%) patients had no
      complaints, 30 (18%) patients had occasional pain, and 19 (12%) patients had no
      improvement. During postoperative follow-up, 8 patients required repeat surgery
      for recurrence or residual fragments. Postoperatively, 4 patients experienced
      dysesthesia, which completely resolved in time. Neurologic deterioration occurred
      in 5 patients, 4 of whom recovered completely without any intervention. Dural
      tears occurred in 6 patients. CONCLUSIONS: Fully endoscopic interlaminar or
      transforaminal surgeries are safe and effective treatment modalities for lumbar
      disc herniations. Despite the difficulties of acquiring this new technique, good
      results can be achieved with sufficient experience.

PMID- 24907439
TI  - The utility and limitations of intraoperative near-infrared indocyanine green
      videoangiography in aneurysm surgery.
AB  - OBJECTIVE: To analyze the clip repositioning rate and the correlation between
      indocyanine green (ICG) videoangiography and conventional postoperative digital
      subtraction angiography for completeness of aneurysm occlusion and parent and
      branching vessel compromise. METHODS: This retrospective study included 112
      patients with 126 aneurysms who underwent microsurgical clipping and ICG
      videoangiography during aneurysm surgery at a single center from January 2008 to
      June 2013. Age, gender, aneurysm size, location, and rupture status were included
      in the model for analysis. RESULTS: In 10 patients (8%), ICG videoangiography
      resulted in clip repositioning during surgery. Discordance between ICG
      videoangiography and postoperative angiography was observed in 5 patients (4%).
      There was no significant difference of ICG videoangiography-postoperative
      angiography discordance between ruptured and unruptured aneurysms (P = 0.56). On
      multivariate analysis, patient age, gender, aneurysm size, and rupture status did
      not reach significance. Ophthalmic internal carotid artery aneurysms were more
      likely to have discordance compared with all other aneurysms (P = 0.04; odds
      ratio, 10.8; confidence interval, 1.5-75.94). CONCLUSIONS: ICG videoangiography
      is a very useful modality for intraoperative assessment of the adequacy of
      aneurysmal obliteration and patency of parent and perforating vessels. However,
      ICG videoangiography is not absolutely reliable as a stand-alone method during
      clipping of ophthalmic artery aneurysms and can be complemented with
      intraoperative digital subtraction angiography. ICG videoangiography can be used
      either as an alternative or as a complementary technique to intraoperative
      digital subtraction angiography during aneurysm surgery.

PMID- 24907440
TI  - Quantitative in vitro-to-in vivo extrapolation in a high-throughput environment.
AB  - High-throughput in vitro toxicity screening provides an efficient way to identify
      potential biological targets for environmental and industrial chemicals while
      conserving limited testing resources. However, reliance on the nominal chemical
      concentrations in these in vitro assays as an indicator of bioactivity may
      misrepresent potential in vivo effects of these chemicals due to differences in
      clearance, protein binding, bioavailability, and other pharmacokinetic factors.
      Development of high-throughput in vitro hepatic clearance and protein binding
      assays and refinement of quantitative in vitro-to-in vivo extrapolation (QIVIVE)
      methods have provided key tools to predict xenobiotic steady state
      pharmacokinetics. Using a process known as reverse dosimetry, knowledge of the
      chemical steady state behavior can be incorporated with HTS data to determine the
      external in vivo oral exposure needed to achieve internal blood concentrations
      equivalent to those eliciting bioactivity in the assays. These daily oral doses,
      known as oral equivalents, can be compared to chronic human exposure estimates to
      assess whether in vitro bioactivity would be expected at the dose-equivalent
      level of human exposure. This review will describe the use of QIVIVE methods in a
      high-throughput environment and the promise they hold in shaping chemical testing
      priorities and, potentially, high-throughput risk assessment strategies. 

PMID- 24907441
TI  - Comparative analysis of 11 Brassicales mitochondrial genomes and the
      mitochondrial transcriptome of Brassica oleracea.
AB  - To elucidate the evolution of mitochondrial genomic diversity within a single
      order of angiosperms, we sequenced seven Brassicales genomes and the
      transcriptome of Brassica oleracea. In the common ancestor of Brassicaceae,
      several genes of known function were lost and the ccmFN gene was split into two
      independent genes, which also coincides with a trend of genome reduction towards
      the smallest sequenced angiosperm genomes of Brassica. For most ORFs of unknown
      function, the lack of conservation throughout Brassicales and the generally low
      expression and absence of RNA editing in B. oleracea argue against functionality.
      However, two chimeric ORFs were expressed and edited in B. oleracea, suggesting a
      potential role in cytoplasmic male sterility in certain nuclear backgrounds.
      These results demonstrate how frequent shifts in size, structure, and content of
      plant mitochondrial genomes can occur over short evolutionary time scales. 

PMID- 24907442
TI  - Demographics of pediatric renal trauma.
AB  - PURPOSE: There is a lack of national data describing the demographics and nature
      of pediatric renal trauma. We used the National Trauma Data Bank to analyze
      mechanisms and grades of injury, demographics and treatment characteristics of
      pediatric renal trauma cases. MATERIALS AND METHODS: Renal injuries were
      identified by Abbreviated Injury Scale codes and converted to American
      Association for the Surgery of Trauma renal injury grades. Patients were
      stratified by age (0 to 1, 2 to 4, 5 to 14 and 15 to 18 years) for more specific
      analyses of mechanisms and grades of injury. Data reviewed included mechanisms
      and grades of renal injury, demographics, and setting and type of treatment.
      RESULTS: A total of 2,213 pediatric renal injuries were converted to American
      Association for the Surgery of Trauma grade. Mean +/- SD age at injury was 13.7
      +/- 4.4 years, with 2,089 patients (94%) being 5 to 18 years old. Of the injuries
      79% were grade I, II or III. Penetrating injury accounted for less than 10% of
      all pediatric renal injuries. A majority of patients (57%) were admitted to
      university hospitals with a dedicated trauma service (73%) and only 12% of
      patients were admitted to a pediatric hospital. A total of 122 nephrectomies
      (5.5%) were performed. CONCLUSIONS: Most renal trauma in children is low grade,
      is blunt in nature and occurs after age 5 years. The majority of these cases are
      managed at adult hospitals. Although most patients are treated conservatively,
      the rate of nephrectomy is 3 times higher at adult hospitals than at pediatric
      centers.

PMID- 24907443
TI  - The overlap and distinction of self-reported symptoms between interstitial
      cystitis/bladder pain syndrome and overactive bladder: a questionnaire based
      analysis.
AB  - PURPOSE: We compared symptoms between interstitial cystitis/bladder pain syndrome
      and overactive bladder based on patient self-reported symptoms on validated
      questionnaires. MATERIALS AND METHODS: We prospectively recruited 26 patients
      diagnosed with interstitial cystitis/bladder pain syndrome, 53 diagnosed with
      overactive bladder and 30 healthy controls to participate in a questionnaire
      based study that inquired about lower urinary tract symptoms. The questionnaires
      used were GUPI, ICSI, ICPI, ICIQ-OAB, ICIQ-UI, IUSS, numerical rating scales of
      the severity of bladder pain, pressure or discomfort, and numerical rating scale
      of the severity of urgency and frequency symptoms. RESULTS: On univariate
      analysis patients with interstitial cystitis/bladder pain syndrome reported
      significantly more severe pain symptoms than those with overactive bladder.
      Patients with overactive bladder reported significantly more severe urinary
      incontinence symptoms than those with interstitial cystitis/bladder pain
      syndrome. There was no difference in frequency and urgency severity between the
      groups. Surprisingly, 33% of patients with overactive bladder reported pain or
      discomfort when the bladder filled and 46% with interstitial cystitis/bladder
      pain syndrome reported urgency incontinence. On multivariate analysis ICIQ-UI
      total scores (p = 0.01) and bladder pain severity on the numerical rating scale
      (p <0.01) distinguished the 2 conditions with 90.6% sensitivity and 96.1%
      specificity. Overactive bladder had higher ICIQ-UI and lower numerical rating
      scale pain scores. CONCLUSIONS: There is considerable overlap of self-reported
      symptoms between interstitial cystitis/bladder pain syndrome and overactive
      bladder. This overlap raises the possibility that the 2 conditions represent a
      continuum of a bladder hypersensitivity syndrome.

PMID- 24907444
TI  - The safety and efficacy of a new adjustable single incision sling for female
      stress urinary incontinence.
AB  - PURPOSE: We describe the safety and efficacy of the Altis((r)) Single Incision
      Sling System for the treatment of female stress urinary incontinence through 12
      months. MATERIALS AND METHODS: In this study we collected a variety of safety and
      efficacy measures relevant to the assessment of urinary incontinence. The primary
      efficacy end point was improvement in 24-hour pad weight test. Other efficacy
      measures included the cough stress test, Urogenital Distress Inventory-Short
      Form, Incontinence Impact Questionnaire-Short Form, Patient Global Impression of
      Improvement and 3-day voiding diary. Safety was evaluated through assessment of
      device and procedure related adverse events. RESULTS: Of 116 surgical attempts
      113 subjects were implanted with the Altis sling. Of these patients 103 had
      primary efficacy data at baseline and 6 months, and 101 had efficacy data at
      baseline and 12 months. Consequently 88 (85.4%) subjects at 6 months and 91
      (90.1%) at 12 months achieved a 50% or greater reduction in pad weight. The cough
      stress test was negative for 95 (92.2%) subjects at 6 months and 91 (90.1%) at 12
      months. A decrease in median leaks per day was observed at 6 months and
      improvements in all patient reported measures were observed through 12 months. A
      majority of subjects reported feeling much better or very much better at 6 and 12
      months, respectively. There were no reports of mesh erosion or migration and no
      unanticipated adverse events through 12 months. CONCLUSIONS: The Altis sling
      appears to be safe and efficacious, and performs as intended in the treatment of
      stress urinary incontinence through 12 months.

PMID- 24907445
TI  - T cell migration in intact lymph nodes in vivo.
AB  - In the lymph node, T cells migrate rapidly and with striking versatility in a
      continuous scan for antigen presenting dendritic cells. The scanning process is
      greatly facilitated by the lymph node structure and composition. In vivo imaging
      has been instrumental in deciphering the spatiotemporal dynamics of intranodal T
      cell migration in both health and disease. Here we review recent developments in
      uncovering the migration modes employed by T cells in the lymph node, the
      underlying molecular mechanisms, and the scanning strategies utilised by T cells
      to ensure a timely response to antigenic stimuli. 

PMID- 24907446
TI  - Abnormal functional connectivity within the default mode network in patients with
      HBV-related cirrhosis without hepatic encephalopathy revealed by resting-state
      functional MRI.
AB  - By means of "task free" resting-state functional magnetic resonance imaging (rs
      fMRI), abnormal functional connectivity (FC) of the default mode network (DMN) in
      cirrhotic patients with hepatic encephalopathy (HE) has been reported; however,
      little is known about the changes of DMN in cirrhotic patients without overt or
      minimal HE. The aim of this study was to investigate whether there was a
      disruption of the FC within the DMN in patients with hepatitis B virus (HBV)
      related cirrhosis without any signs of HE. Fifty one patients with HBV-related
      cirrhosis without HE and 61 age- and gender-matched healthy controls underwent
      the rs-fMRI. Seed-based region-to-region FC was used to analyze the connectivity
      between each pair of regions within the DMN, including posterior cingulate cortex
      (PCC), medial prefrontal cortex (mPFC), hippocampal formation (HF), inferior
      parietal cortex (IPC), and medial temporal lobe (MTL). Pearson correlation
      analysis was performed between the abnormal FC strength within the DMN and venous
      blood ammonia levels in patients. Compared with the controls, patients with HBV
      related cirrhosis without HE demonstrated significantly decreased region-to
      region FC between the mPFC and bilateral MTL, right HF, and left IPC, as well as
      between the right MTL and left IPC, right HF, and PCC. A significant negative
      relationship was observed between blood ammonia levels and connectivity strength
      between the mPFC and left IPC in patients. These results suggest that patients
      with HBV-related cirrhosis without HE had disrupted functional connectivty within
      the DMN, even before the appearance of minimal HE. 

PMID- 24907447
TI  - Specialized filopodia: at the 'tip' of morphogen transport and vertebrate tissue
      patterning.
AB  - For over a century, biologists have strived to unravel the mechanisms that
      establish how cells are informed of their position in the embryo and
      differentiate to give rise to complex organs and structures. However, the
      historical idea that one predominant mode of ligand transport, largely accounted
      for by free diffusion, can explain how all signaling molecules, known as
      morphogens, control tissue patterning has greatly hindered our ability to fully
      appreciate the complexities driving the delivery and reception of signaling
      molecules at a distance. In reality, a cell's shape, morphology, and location
      change continuously as development progresses. Thus, cellular context poses
      distinct challenges for morphogen transport in each unique cellular environment.
      Emerging studies reveal that some cells overcome such obstacles in an unexpected
      manner: via long, cellular projections, or specialized filopodia, that link
      distant cells and traffic signaling components. Here, we will review recent
      findings describing specialized filopodia and discuss the potential mechanisms
      and implications for filopodia-based long-range cell signaling and communication,
      particularly within the developing vertebrate embryo. 

PMID- 24907448
TI  - The architecture of gene expression: integrating dispersed cis-regulatory modules
      into coherent regulatory domains.
AB  - Specificity and precision of expression are essential for the genes that regulate
      developmental processes. The specialized cis-acting modules, such as enhancers,
      that define gene expression patterns can be distributed across large regions,
      raising questions about the nature of the mechanisms that underline their action.
      Recent data has exposed the structural 3D context in which these long-range
      enhancers are operating. Here, we present how these studies shed new light on
      principles driving long-distance regulatory relationships. We discuss the
      molecular mechanisms that enable and accompany the action of long-range acting
      elements and the integration of multiple distributed regulatory inputs into the
      coherent and specific regulatory programs that are key to embryonic development. 

PMID- 24907449
TI  - Direct plantlet inoculation with soil or insect-associated fungi may control
      cabbage root fly maggots.
AB  - A potential Delia radicum biological control strategy involving cauliflower
      plantlet inoculation with various fungi was investigated in a series of
      laboratory and glasshouse experiments. In addition to entomopathogenic fungi,
      fungi with a high rhizosphere competence and fungi with the ability to survive as
      saprotrophs in soil were tested. The following fungal species were evaluated in
      the experiments: Trichoderma atroviride, T. koningiopsis, T. gamsii, Beauveria
      bassiana, Metharhizium anisopliae, M. brunneum and Clonostachys solani. A
      commercial carbosulfan-based insecticide was used as a positive control.
      Additionally, two commercial products, one based on B. bassiana (Naturalis) and
      one on Bacillus thuringiensis (Delfin) were used as reference biocontrol agents.
      The aims were (i) to assess the pathogenicity of the selected fungal isolates to
      Delia radicum, (ii) to evaluate the fungal isolates' rhizosphere competence, with
      the emphasis on the persistence of the original inoculum on the growing roots,
      (iii) to assess possible endophytic plant tissue colonization, and (iv) to
      evaluate potential plant growth stimulating effects of the added inoculi.
      Significant pathogenicity of tested fungi against Delia radicum was confirmed in
      in vitro and glasshouse experiments. All tested fungi persisted on cauliflower
      rhizoplane. More importantly, the added fungi were found on thoroughly washed
      roots outside the original point of inoculation. This provided us with evidence
      that our tested fungi could be transferred via or grow with the elongating roots.
      In addition to colonizing the rhizoplane, some fungi were found inside the plant
      root or stem tissue, thus exhibiting endophytic characteristics. The importance
      of fungal ecology as a criterion in appropriate biological control agent
      selection is discussed. 

PMID- 24907450
TI  - Neural correlates of music-syntactic processing in two-year old children.
AB  - Music is a basic and ubiquitous socio-cognitive domain. However, our
      understanding of the time course of the development of music perception,
      particularly regarding implicit knowledge of music-syntactic regularities,
      remains contradictory and incomplete. Some authors assume that the acquisition of
      knowledge about these regularities lasts until late childhood, but there is also
      evidence for the presence of such knowledge in four- and five-year-olds. To
      explore whether such knowledge is already present in younger children, we tested
      whether 30-month-olds (N=62) show neurophysiological responses to music
      syntactically irregular harmonies. We observed an early right anterior negativity
      in response to both irregular in-key and out-of-key chords. The N5, a brain
      response usually present in older children and adults, was not observed,
      indicating that processes of harmonic integration (as reflected in the N5) are
      still in development in this age group. In conclusion, our results indicate that
      30-month-olds already have acquired implicit knowledge of complex harmonic music
      syntactic regularities and process musical information according to this
      knowledge. 

PMID- 24907451
TI  - The effect of small intestine heterogeneity on irreversible electroporation
      treatment planning.
AB  - Nonthermal irreversible electroporation (NTIRE) is an ablation modality that
      utilizes microsecond electric fields to produce nanoscale defects in the cell
      membrane. This results in selective cell death while preserving all other
      molecules, including the extracellular matrix. Here, finite element analysis and
      experimental results are utilized to examine the effect of NTIRE on the small
      intestine due to concern over collateral damage to this organ during NTIRE
      treatment of abdominal cancers. During previous studies, the electrical treatment
      parameters were chosen based on a simplified homogeneous tissue model. The small
      intestine, however, has very distinct layers, and a more realistic model is
      needed to further develop this technology for precise clinical applications. This
      study uses a two-dimensional finite element solution of the Laplace and heat
      conduction equations to investigate how small intestine heterogeneities affect
      the electric field and temperature distribution. Experimental results obtained by
      applying NTIRE to the rat small intestine in vivo support the heterogeneous
      effect of NTIRE on the tissue. The numerical modeling indicates that the
      electroporation parameters chosen for this study avoid thermal damage to the
      tissue. This is supported by histology obtained from the in vivo study, which
      showed preservation of extracellular structures. The finite element model also
      indicates that the heterogeneous structure of the small intestine has a
      significant effect on the electric field and volume of cell ablation during
      electroporation and could have a large impact on the extent of treatment. The
      heterogeneous nature of the tissue should be accounted for in clinical treatment
      planning. 

PMID- 24907452
TI  - An experimental test of the testosterone mediated oxidation handicap hypothesis
      in a wild bird.
AB  - The oxidation handicap hypothesis (OHH) proposed that honesty in sexual signals
      is maintained when testosterone simultaneously promotes the development of
      elaborate signals and imposes an oxidative cost. Although there is evidence that
      testosterone enhances display traits in some cases, relatively few studies have
      tested the prediction that testosterone generates oxidative costs. We tested this
      prediction experimentally by administering testosterone (n=14) and control (n=14)
      implants to free-living common yellowthroat warblers (Geothlypis trichas) and
      quantifying testosterone and oxidative state before and 35+/-15days after
      implantation. We interpreted our experimental results in the context of a larger
      database of 83 unmanipulated males observed over five breeding seasons. In our
      observational data, testosterone was related to aspects of the carotenoid-based
      bib, but these relationships were age-dependent. Bib coloration was related to
      testosterone only for first time breeders, while bib size was positively and
      negatively associated with testosterone among experienced and inexperienced
      breeders, respectively. Two measures of oxidative metabolism-damage to DNA and
      total antioxidant capacity (TAC)-were unrelated to endogenous testosterone.
      Despite the correlation between endogenous testosterone and plumage, our
      experimental results failed to support the key prediction of the OHH.
      Testosterone treated males had higher levels of TAC upon recapture, but oxidative
      damage to DNA did not differ from controls. Because antioxidants can protect
      against the harmful effects of oxidative stress, one interpretation of our
      results is that males physiologically compensated for elevated testosterone,
      avoiding the honesty enforcing mechanism of the OHH. Taken together, our results
      suggest that testosterone is not a direct mediator of honest signaling in
      yellowthroats via its effects on oxidative stress. 

PMID- 24907453
TI  - Heightened aggression and winning contests increase corticosterone but decrease
      testosterone in male Australian water dragons.
AB  - Water dragons (Intellegama [Physignathus] lesueurii) are large (to >1m) agamid
      lizards from eastern Australia. Males are fiercely combative; holding a territory
      requires incessant displays and aggression against other males. If a dominant
      male is absent, injured or fatigued, another male soon takes over his territory.
      Our sampling of blood from free-ranging adult males showed that baseline levels
      of both testosterone and corticosterone were not related to a male's social
      tactic (territorial versus non-territorial), or his frequency of advertisement
      display, aggression, or courtship behavior. Even when we elicited intense
      aggression by non-territorial males (by temporarily removing territory owners),
      testosterone did not increase with the higher levels of aggression that ensued.
      Indeed, testosterone levels decreased in males that won contests. In contrast,
      male corticosterone levels increased with the heightened aggression during
      unsettled conditions, and were higher in males that won contests. High chronic
      male-male competition in this dense population may favor high testosterone levels
      in all adult males to facilitate advertisement and patrol activities required for
      territory maintenance (by dominant animals), and to maintain readiness for
      territory take-overs (in non-territorial animals). Corticosterone levels
      increased in response to intense aggression during socially unstable conditions,
      and were higher in contest winners than losers. A positive correlation between
      the two hormones during socially unstable conditions suggests that the high
      stress of contests decreased androgen production. The persistent intense
      competition in this population appears to exact a high physiological cost, which
      together with our observation that males sometimes lose their territories to
      challengers may indicate cycling between these two tactics to manage long-term
      energetic costs. 

PMID- 24907454
TI  - Stereoselectivity in bioaccumulation and excretion of epoxiconazole by mealworm
      beetle (Tenebrio molitor) larvae.
AB  - Stereoselectivity in bioaccumulation and excretion of stereoisomers of
      epoxiconazole by mealworm beetle (Tenebrio molitor) larvae through dietary
      exposure was investigated. Liquid chromatography tandem mass spectrometry (HPLC
      MS/MS) method that use a ChiralcelOD-3R[cellulosetris-Tris-(3, 5-dichlorophenyl
      carbamate)] chromatography column was applied to carry out chiral separation of
      the stereoisomers. Wheat bran was spiked with racemic epoxiconazole at two dose
      levels of 20mg/kg and 2mg/kg (dry weight) to feed T. molitor larvae. The results
      showed that both the doses of epoxiconazole were taken up by Tenebrio molitor
      larvae rapidly at the initial stages. There was a significant trend of
      stereoselective bioaccumulation in the larvae with a preferential accumulation of
      (-)-epoxiconazole in the 20mg/kg dose. The stereoselectivity in bioaccumulation
      in the 2mg/kg dosage was not obvious compared to the 20mg/kg group. Results of
      excretion indicated an active excretion is an important pathway for the larvae to
      eliminate epoxiconazole which was a passive transport process with non
      stereoselectivity. The faster elimination might be the reason for the low
      accumulation of epoxiconazole, as measured by bioaccumulation factor (BAF).

PMID- 24907455
TI  - Preparation, characterization and efficiency of nanoencapsulated imidacloprid
      under laboratory conditions.
AB  - In this work, nano-imidacloprid was prepared by direct encapsulation with ABA
      triblock linear dendritic copolymers composed of poly(citric acid) (PCA) as A
      block and poly(ethylene glycol) (PEG) as B block. Nanocapsules of imidacloprid
      were characterized using spectroscopy, microscopy and thermal analysis. The
      encapsulation process was performed by self-assembly of PCA-PEG-PCA in the
      presence of imidacloprid in different solvents. Comparison of the TEM images of
      nano-imidacloprid prepared in ethanol and water showed that, during the first
      day, self-assemblies appeared as small particles with an average size of 10-20nm.
      Depending upon the type of solvent, the time and concentration, morphology and
      size of the nano-imidacloprid varied from fiber-like to globular to tubular from
      10nm to several mm in size. Higher loading capacity and slower release rate of
      imidacloprid from nano-imidacloprid at optimum pH of Glyphodes pyloalis's gut
      (pH=10) compared to neutral pH confirmed the selective and controllable action of
      nano-imidacloprid. Results of bioassays on the model insect showed that by using
      the nanoform of imidacloprid, essential dosage of pesticide and environmental
      risk decreased significantly and indicated good performance for this formulation.

PMID- 24907456
TI  - Epigenetic modifier-induced biosynthesis of novel acetylenic sterols from
      Cladosporium colocasiae.
AB  - The addition of an HDAC inhibitor, suberoylanilide hydroxamic acid (SBHA), to the
      culture medium of Cladosporium colocasiae, dramatically altered its metabolic
      profiles. Analysis of the culture broth extract led to the isolation of two new
      acetylenic sterols (1-2). The isolated compounds were further evaluated for their
      cytotoxic and antibacterial activities. Compound 1 showed activity against
      Bacillus subtilis, affording a zone of inhibition of 12mm at 100MUg/disk.
      However, none of them showed noticeable growth inhibitory effects. 

PMID- 24907457
TI  - Phylogenetic and syntenic analyses of the 12-spanner drug:H(+) antiporter family
      1 (DHA1) in pathogenic Candida species: evolution of MDR1 and FLU1 genes.
AB  - Candida albicans and other pathogenic Candida species can develop resistance to
      clinical fungicides through active drug export mediated by multidrug efflux
      pumps, in particular by members of the drug:H(+) antiporter family 1 (DHA1). The
      DHA1 proteins encoded in the genomes of 31 hemiascomycetous strains from 25
      species were identified and homology relationships between these proteins and the
      functionally characterised DHA1 in the model yeast Saccharomyces cerevisiae were
      established. Gene neighbourhood analysis allowed the reconstruction of sixteen
      DHA1 lineages conserved during the CTG complex species evolution. The
      evolutionary history of C. albicans MDR1 and FLU1 genes and Candida dubliniensis,
      Candida tropicalis and Candida parapsilosis MDR1 genes was detailed. Candida
      genomes show an abundant number of MDR1 and FLU1 homologues but the chromosome
      environment where MDR1 homologues reside was poorly conserved during evolution.
      Gene duplication and loss are major mechanisms underlying the evolution of the
      DHA1 genes in Candida species. 

PMID- 24907458
TI  - Familial 46,XY sex reversal without campomelic dysplasia caused by a deletion
      upstream of the SOX9 gene.
AB  - BACKGROUND: 46,XY sex reversal is a rare disorder and familial cases are even
      more rare. The purpose of the present study was to determine the molecular basis
      for a family with three affected siblings who had 46,XY sex reversal. METHODS:
      DNA was extracted from three females with 46,XY sex reversal, two normal sisters,
      and both unaffected parents. All protein coding exons of the SRY and NR5A1 genes
      were subjected to PCR-based DNA sequencing. In addition, array comparative
      genomic hybridization was performed on DNA from all seven family members. A
      deletion was confirmed using quantitative polymerase chain reaction. Expression
      of SOX9 gene was quantified using reverse transcriptase polymerase chain
      reaction. RESULTS: A 349kb heterozygous deletion located 353kb upstream of the
      SOX9 gene on the long arm of chromosome 17 was discovered in the father and three
      affected siblings, but not in the mother. The expression of SOX9 was
      significantly decreased in the affected siblings. Two of three affected sisters
      had gonadoblastomas. CONCLUSION: This is the first report of 46,XY sex reversal
      in three siblings who have a paternally inherited deletion upstream of SOX9
      associated with reduced SOX9 mRNA expression.

PMID- 24907459
TI  - Supplemental choline does not attenuate the effects of neonatal ethanol
      administration on habituation of the heart rate orienting response in rats.
AB  - Several studies using rodent subjects have now shown that extra dietary choline
      may prevent or even reverse the deleterious effects of pre- and early post-natal
      ethanol administration. Choline supplementation has been shown to attenuate many,
      although not all, of ethanol's effects on brain development and behavior. Our
      laboratory has consistently reported impaired habituation of the heart rate
      orienting response to a novel olfactory stimulus in animals exposed to ethanol on
      postnatal days (PD) 4-9. Here we examine whether supplemental choline given both
      during and after ethanol administration could alleviate these ethanol-induced
      deficits. Subjects were given 5g/kg/day ethanol or sham intubations on PD 4-9.
      Half of the subjects in each group were given a single daily s.c. injection of
      choline chloride on PD 4-20, while the other half were injected daily with
      saline. Pups were tested for heart rate orienting and response habituation in a
      single test session on PD 23. Results replicated the ethanol-induced impairment
      in response habituation. However, choline supplementation had no effect on
      orienting or habituation in either neonatal treatment group. These findings
      indicate that habituation deficits induced by ethanol are not alleviated by extra
      dietary choline using these parameters. Choline holds great promise as a
      treatment for some fetal alcohol effects, but is not an effective treatment for
      all ethanol-related deficits. 

PMID- 24907460
TI  - Transmembrane helix assembly and the role of salt bridges.
AB  - Transmembrane helix-helix interactions mediate the folding and assembly of
      membrane proteins. Recognition motifs range from GxxxG and leucine zippers to
      polar side chains and salt bridges. Some canonical membrane proteins contain
      local charge clusters that are important for folding and function, and which have
      to be compatible with a stable insertion into the bilayer via the translocon.
      Recently, the electrostatic "charge zipper" has been described as another kind of
      assembly motif. The protein sequences exhibit a quasi-symmetrical pattern of
      complementary charges that can form extended ladders of salt bridges. Such
      segments can insert reversibly into membranes, or even translocate across them.
      Nature uses charge zippers in transport processes, and they can also be adapted
      in the design of cell-penetrating carriers.

PMID- 24907461
TI  - Larval morphology of Atherigona orientalis (Schiner) (Diptera: Muscidae) -a
      species of sanitary and forensic importance.
AB  - Larval morphology is documented using both light and scanning electron microscopy
      for all three instars of the muscid fly Atherigona orientalis (Schiner), which is
      a species of known sanitary and forensic importance found in tropical and
      subtropical areas of all biogeographic regions. The unpaired sclerite in a form
      of a spicule is reported herein in the second and the third instar larvae.
      Occurrence of this sclerite was hitherto unknown in the second instar larvae of
      Muscidae and was only known from the third instar of several species, however not
      in a form of a spicule. Our study is the first report of the occurrence of the
      "sensory organ X" in all three larval instars of a species representing the
      family Muscidae. The bubble membrane, previously known only from third instar
      cyclorrhaphan larvae, is reported herein for the first time in the second instar.
      Characters allowing for discrimination of A. orientalis larvae from other
      forensically important Muscidae are summarised. 

PMID- 24907462
TI  - Differences in male-female ratios of Aedes albopictus (Diptera: Culicidae)
      following ultra-low volume adulticide applications.
AB  - Suppression of Aedes albopictus populations is a substantial challenge for
      mosquito control programs globally because juveniles of this species are found in
      numerous kinds of domestic artificial containers that are difficult to detect,
      access, and eliminate. We conducted a multi-year assessment of the effect of
      different interventions to control Ae. albopictus near the northernmost
      geographic boundary of the species in temperate North America and deployed an
      array of BG-Sentinel traps for adult surveillance. Here we present the results of
      a comparative examination of adult sex ratios in urban and suburban areas, shifts
      in sex ratios after control interventions, and a discussion of the critical
      drivers of population dynamics of Ae. albopictus in our area. We collected
      significantly more male mosquitoes in urban as compared to suburban areas in June
      through September, but not in May (p<0.001). The higher number of male mosquitoes
      in urban areas could be attributed to a higher number of larval habitats within a
      closer proximity of the surveillance traps and the lower flight dispersal of
      males. Following application of adulticides in urban areas, Ae. albopictus male
      populations were reduced by 88% on average, which was higher than the 69%
      reduction in female populations. The higher reduction of male mosquitoes could be
      attributed to the smaller body mass of the males and their higher susceptibility
      to adulticides. The results of this study are directly relevant to the
      development of suitable control strategies that depend on manipulation of males,
      such as the sterile insect technique. The results could also be used to refine
      mosquito abatement by providing more accurate methods to determine the need and
      timing of vector control. 

PMID- 24907463
TI  - A self-assembling nanomaterial reduces acute brain injury and enhances functional
      recovery in a rat model of intracerebral hemorrhage.
AB  - There is no effective treatment for intracerebral hemorrhage (ICH). Intracerebral
      delivery of nanomaterials into the hemorrhagic lesion may be a new therapeutic
      strategy. In a rat model of ICH plus ultra-early hematoma aspiration, we found
      that locally delivered self-assembling peptide nanofiber scaffold (SAPNS)
      replaced the hematoma, reduced acute brain injury and brain cavity formation, and
      improved sensorimotor functional recovery. SAPNS serves as biocompatible material
      in the hemorrhagic brain cavity. Local delivery of this nanomaterial may
      facilitate the repair of ICH related brain injury and functional recovery. From
      the clinical editor: In a rat model of intracranial hemorrhage, these authors
      demonstrate that following ultra-early hematoma aspiration, local delivery of a
      self-assembling peptide nanofiber scaffold replaces the hematoma, reduces brain
      cavity formation, and improves sensorimotor functional recovery. Similar
      approaches would be welcome additions to the clinical treatment of this often
      devastating condition.

PMID- 24907465
TI  - Visual enhancement of auditory beat perception across auditory interference
      levels.
AB  - This study dealt with audiovisual rhythm perception involving an observed
      movement. Two experiments investigated whether a visual beat conveyed by a
      bouncing human point-light figure facilitated beat perception of concurrent
      auditory rhythms, and whether this enhancement followed a profile of multisensory
      integration. In Experiment 1, participants listened to three repetitions of a
      metrically simple rhythm and detected a perturbation in the third repetition. The
      rhythm was presented alone or with a visual beat in phase to it. Both conditions
      were presented with or without an auditory interference sequence at four
      increasing tempi, which served to progressively weaken the beat of the auditory
      rhythm. In Experiment 2, participants tapped to a regular auditory beat in the
      same combinations of visual beat and auditory interference. Results showed that
      the visual beat improved the perception of (Experiment 1) and the synchronization
      to (Experiment 2) the auditory rhythms. Moreover, in both experiments, visual
      enhancement was greater when the performance in the unisensory (auditory)
      conditions was poorer, consistent with the principle of inverse effectiveness.
      The relative multisensory gain increased as auditory performance deteriorated,
      except in one intermediate level. Together these results demonstrate that
      rhythmic visual movement aids auditory rhythm perception, which may be subserved
      by a perceptually integrated audiovisual beat that couples the internal motor
      system. 

PMID- 24907464
TI  - Small molecule delivery through nanofibrous scaffolds for musculoskeletal
      regenerative engineering.
AB  - Musculoskeletal regenerative engineering approach using small bioactive molecules
      in conjunction with advanced materials has emerged as a highly promising strategy
      for musculoskeletal repair and regeneration. Advanced biomaterials technologies
      have revealed nanofiber-based scaffolds for musculoskeletal tissue engineering as
      vehicles for the controlled delivery of small molecule drugs. This review article
      highlights recent advances in nanofiber-based delivery of small molecules for
      musculoskeletal regenerative engineering. The article concludes with perspectives
      on the challenges and future directions. FROM THE CLINICAL EDITOR: In this
      review, advances in nanofiber-based delivery of small molecules are discussed
      from the standpoint of their potential role in musculoskeletal regenerative
      engineering, highlighting both future directions and current challenges.

PMID- 24907466
TI  - Stable isotopes in tree rings: towards a mechanistic understanding of isotope
      fractionation and mixing processes from the leaves to the wood.
AB  - The mechanistic understanding of isotope fractionation processes is increasing
      but we still lack detailed knowledge of the processes that determine the isotopic
      composition of the tree-ring archive over the long term. Especially with regard
      to the path from leaf photosynthate production to wood formation, post
      assimilation fractionations/processes might cause at least a partial decoupling
      between the leaf isotope signals that record processes such as stomatal
      conductance, transpiration and photosynthesis, and the wood or cellulose signals
      that are stored in the paleophysiological record. In this review, we start from
      the rather well understood processes at the leaf level such as photosynthetic
      carbon isotope fractionation, leaf water evaporative isotope enrichment and the
      issue of the isotopic composition of inorganic sources (CO2 and H2O), though we
      focus on the less explored 'downstream' processes related to metabolism and
      transport. We further summarize the roles of cellulose and lignin as important
      chemical constituents of wood, and the processes that determine the transfer of
      photosynthate (sucrose) and associated isotopic signals to wood production. We
      cover the broad topics of post-carboxylation carbon isotope fractionation and of
      the exchange of organic oxygen with water within the tree. In two case studies,
      we assess the transfer of carbon and oxygen isotopic signals from leaves to tree
      rings. Finally we address the issue of different temporal scales and link isotope
      fractionation at the shorter time scale for processes in the leaf to the isotopic
      ratio as recorded across longer time scales of the tree-ring archive. 

PMID- 24907467
TI  - The effects of erythropoietin signaling on telomerase regulation in non-erythroid
      malignant and non-malignant cells.
AB  - Treatment with erythropoietin (EPO) in several cancers is associated with
      decreased survival due to cancer progression. Due to the major importance of
      telomerase in cancer biology we hypothesized that some of these effects may be
      mediated through EPO effect on telomerase. For this aim we explored the possible
      effects of EPO on telomerase regulation, cell migration and chemosensitivity in
      non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase
      activity (TA) and cell migration increased in response to EPO. EPO had no effect
      on cancer cells sensitivity to cisplatinum and on the cell cycle status. The
      inhibition of telomerase modestly repressed the proliferative effect of EPO.
      Telomere shortening caused by long term inhibition of the enzyme abolished the
      effect of EPO, suggesting that EPO effects on cancer cells are related to
      telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA
      was mediated post-translationally through the Lyn-Src and not the canonical JAK2
      pathway. 

PMID- 24907468
TI  - Association between age at diagnosis and degree of liver injury in hepatitis C.
AB  - INTRODUCTION: A population-based survey conducted in Brazilian capital cities
      found that only 16% of the population had ever been tested for hepatitis C. These
      data suggest that much of the Brazilian population with HCV infection remains
      undiagnosed. The distribution of age ranges at diagnosis and its association with
      the degree of hepatitis C are still unknown in Brazilian patients. MATERIAL AND
      METHODS: Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche),
      were included in the study. Patients with HBV or HIV coinfection, autoimmune
      diseases, or alcohol intake>20 g/day were excluded. HCV genotyping was performed
      by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche).
      The METAVIR classification was used to assess structural liver injury. The Chi
      square (chi(2)) test and student's t-test were used for between-group
      comparisons. Spearman's rank correlation coefficient were used for analysing the
      correlation between parameters. RESULTS: A total of 525 charts were reviewed. Of
      the patients included, 49.5% were male, only 10% of the patients were aged less
      than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years
      age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV
      subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b.
      According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8%
      F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated
      significantly with fibrosis (rs=0.307, p<0.001). The degree of fibrosis increased
      with advancing age. Only age at diagnosis and fasting blood glucose were
      independently associated with disease stage. Those patients with subtype 1a had
      higher prevalence of F2-F4 than those with subtype 1b. CONCLUSION: In Brazil,
      diagnosis of hepatitis C is more commonly established in older patients (age 45
      60 years) with more advanced disease. Reassessment of strategies for hepatitis C
      diagnosis in the country is required.

PMID- 24907469
TI  - Efficacy of tigecycline, polymyxin, gentamicin, meropenem and associations in
      experimental Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae
      non-lethal sepsis.

PMID- 24907471
TI  - Sixth case of infective endocarditis caused by Gemella bergeri.

PMID- 24907470
TI  - Spontaneous pneumothorax: a fatal complication in HIV-infected patients.

PMID- 24907472
TI  - Sclerosing encapsulating peritonitis in HIV-infected patient on dialysis.

PMID- 24907473
TI  - Absence of legionellosis in patients with community-acquired pneumonia requiring
      hospitalization.

PMID- 24907474
TI  - Immunomodulatory properties of cell wall extract from Enterococcus faecalis
      CECT7121.
AB  - The aim of this study was to investigate the immunomodulatory properties of cell
      wall extract from Enterococcus faecalis CECT7121, measuring the induction of
      cytokines TNF-alpha, IL-6, IL-10 and IL-12 from human peripheral blood
      mononuclear cells (PBMCs). Cell wall extract was prepared from their growth in
      brain heart infusion broth (18h, 35 degrees C). Subsequently, toxicity of the
      obtained cell wall extract was tested in Balb-C mice. PBMCs were isolated from
      buffy coats at the Blood Transfusion Service of Hospital Ramon Santamarina
      (Tandil, Argentina). PBMCs were purified using standard Ficoll-Paque gradient
      centrifugation. Aliquots of purified leukocytes were incubated at 37 degrees C
      for 24h with heat-killed E. faecalis CECT7121 and cell wall extract.
      Concentrations of IL-6, TNFalpha, IL-10 and IL-12 (p70) were measured by solid
      phase sandwich ELISA. Changes in appearance and behavior of mice were evidenced
      only in the group with the maximal concentration of wall cell extract used
      (10,000MUg). Cell wall extract and heat-killed E. faecalis CECT7121 induced the
      production of significantly higher amounts of Il-12, IL-6, TNF-alpha and IL-10
      cytokines compared to the nonstimulated PBMCs. These findings provide helpful
      information on immunomodulation activity by cell wall extract in sight of the
      application of this compound in controlling certain infectious diseases. 

PMID- 24907475
TI  - Amyloid fibrils compared to peptide nanotubes.
AB  - Prefibrillar oligomeric states and amyloid fibrils of amyloid-forming proteins
      qualify as nanoparticles. We aim to predict what biophysical and biochemical
      properties they could share in common with better researched peptide nanotubes.
      We first describe what is known of amyloid fibrils and prefibrillar aggregates
      (oligomers and protofibrils): their structure, mechanisms of formation and
      putative mechanism of cytotoxicity. In distinction from other neuronal fibrillar
      constituents, amyloid fibrils are believed to cause pathology, however, some can
      also be functional. Second, we give a review of known biophysical properties of
      peptide nanotubes. Finally, we compare properties of these two macromolecular
      states side by side and discuss which measurements that have already been done
      with peptide nanotubes could be done with amyloid fibrils as well. 

PMID- 24907476
TI  - Influence of high-flux hemodialysis and hemodiafiltration on serum C-terminal
      agrin fragment levels in end-stage renal disease patients.
AB  - C-terminal agrin fragment (CAF, 22 kDa) has been shown to be a promising new
      rapid biomarker for kidney function. This study evaluated the influence of
      hemodialysis (HD) and hemodiafiltration (HDF) treatment on serum CAF
      concentrations in patients with end-stage renal disease (ESRD). A total of 36
      patients with ESRD undergoing chronic HD/HDF treatment were enrolled (21 high
      flux-HD/Fx60 membrane, 7 high-flux-HD/Elisio19H membrane, and 8 HDF/Elisio19H
      membrane). On a midweek session, blood samples were obtained before, at halftime,
      and post-treatment. Dialysate samples were obtained 4 times during treatment.
      Serum and dialysate CAF, cystatin C, urea, and creatinine concentrations were
      measured. Reduction ratios (RRs), total solute removal, overall dialytic
      clearance, and instantaneous dialytic clearance at halftime were calculated and
      compared. Although HD/Elisio19H and HDF/Elisio19H treatments significantly
      reduced CAF concentrations (RR 46.6 +/- 9.1% and 57.6 +/- 11.7%, respectively, P
      = 0.018 and P = 0.001), HD/Fx60 treatment did not remove CAF from serum (RR 2.4
      +/- 15.4%, P = 0.25), there was no relevant CAF detection in dialysate. In the
      HD/Fx60 group, the RR of CAF was significantly lower compared with cystatin C,
      urea, and creatinine, in which significant removal was detected (37.9 +/- 14.8%,
      65.0 +/- 10.7%, and 56.0 +/- 9.8%, respectively, P < 0.001). CAF is a new
      biomarker for kidney function whose serum concentration is not influenced by
      conventional high-flux HD using Fx60 membrane. It might therefore represent a
      promising dialysis-independent biomarker for evaluation of kidney function, for
      example, in acute kidney failure. 

PMID- 24907477
TI  - A novel androgen receptor gene mutation in a patient with congenital adrenal
      hyperplasia associated with penoscrotal hypospadias.
AB  - Congenital adrenal hyperplasia (CAH) associated with penoscrotal hypospadias is a
      rare case of disorders of sex development. Here, we report clinical, genetic,
      biochemical, and molecular findings in a 2-year-old infant with CAH and
      penoscrotal hypospadias. Chromosomal analysis revealed 46,XX karyotype. Hormonal
      investigations indicated low levels of cortisol and elevated levels of
      testosterone, 17-hydroxyprogesterone, and androstenedione hormone. Molecular
      genetic testing of androgen receptor (AR) gene identified a novel homozygous
      missense mutation of single nucleotide transition G to A at position 2058
      (GenBank accession number GU784855), resulting in amino acid interchange alanine
      to threonine at codon 566 in exon 2 (Ala566Thr) (GenBank Protein_id ADD26777.1).
      The nature of the mutation presented is in the highly conserved DNA-binding
      domain of the AR gene. The novel mutation identified in the rare genetic disorder
      provides additional support to the previously reported genotype-phenotype
      correlations, and our finding has expanded the spectrum of known mutations of the
      AR gene.

PMID- 24907478
TI  - Benthic flux of dissolved organic matter from lake sediment at different redox
      conditions and the possible effects of biogeochemical processes.
AB  - The benthic fluxes of dissolved organic carbon (DOC), chromophoric and
      fluorescent dissolved organic matter (CDOM and FDOM) were studied for the
      sediment from an artificial lake, based on laboratory benthic chamber
      experiments. Conservative estimates for the benthic flux of DOC were 71 +/- 142
      and 51 +/- 101 mg m(-2) day(-1) at hypoxic and oxic conditions, respectively. Two
      humic-like (C1 and C2), one tryptophan-like (C3), and one microbial humic-like
      (C4) components were identified from the samples using fluorescence excitation
      emission matrices and parallel factor analysis (EEM-PARAFAC). During the
      incubation period, C3 was removed while C4 was accumulated in the overlying water
      with no significant difference in the trends between the redox conditions. The
      humification index (HIX) increased with time. The combined results for C3, C4 and
      HIX suggested that microbial transformation may be an important process affecting
      the flux behaviors of DOM. In contrast, the overall accumulations of CDOM, C1,
      and C2 in the overlying water occurred only for the hypoxic condition, which was
      possibly explained by their enhanced photo-degradation and sorption to redox
      sensitive minerals under the oxic condition. Our study demonstrated significant
      benthic flux of DOM in lake sediment and also the possible involvement of
      biogeochemical transformation in the processes, providing insight into carbon
      cycling in inland waters.

PMID- 24907479
TI  - Plant-integrated measurement of greenhouse gas emissions from a municipal
      wastewater treatment plant.
AB  - Wastewater treatment plants (WWTPs) contribute to anthropogenic greenhouse gas
      (GHG) emissions. Due to its spatial and temporal variation in emissions, whole
      plant characterization of GHG emissions from WWTPs face a number of obstacles. In
      this study, a tracer dispersion method was applied to quantify plant-integrated,
      real-time emissions of methane and nitrous oxides. Two mobile cavity ring-down
      spectroscopy sampling devices were used to record downwind gas concentrations
      emitted from a municipal WWTP situated in Copenhagen, Denmark. This plant is
      equipped to remove biological nitrogen and employs anaerobic digestion for sludge
      stabilization. Over the course of nine measurement campaigns, a wide range of
      emissions were detected: methane from 4.99 kg h(-1) up to 92.3 kg h(-1) and
      nitrous oxide from below the detection limit (0.37 kg h(-1)) up to 10.5 kg h(-1).
      High emissions were observed during periods experiencing operational problems,
      such as during foaming events in anaerobic digesters and during sub-optimal
      operation of biological nitrogen removal in the secondary treatment of
      wastewater. Methane emissions detected during measurement campaigns corresponded
      to 2.07-32.7% of the methane generated in the plant. As high as 4.27% of nitrogen
      entering the WWTP was emitted as nitrous oxide under the sub-optimal operation of
      biological treatment processes. The study shows that the unit process
      configuration, as well as the operation of the WWTP, determines the rate of GHG
      emission. The applied plant-integrated emission measurement method could be used
      to ease the burden of quantifying GHG emissions from WWTPs for reporting purposes
      and could contribute to the development of more accurate depictions of
      environmental performance of WWTPs.

PMID- 24907480
TI  - Effect of ultrasound, low-temperature thermal and alkali pre-treatments on waste
      activated sludge rheology, hygienization and methane potential.
AB  - Waste activated sludge is slower to biodegrade under anaerobic conditions than is
      primary sludge due to the glycan strands present in microbial cell walls. The use
      of pre-treatments may help to disrupt cell membranes and improve waste activated
      sludge biodegradability. In the present study, the effect of ultrasound, low
      temperature thermal and alkali pre-treatments on the rheology, hygienization and
      biodegradability of waste activated sludge was evaluated. The optimum condition
      of each pre-treatment was selected based on rheological criteria (reduction of
      steady state viscosity) and hygienization levels (reduction of Escherichia coli,
      somatic coliphages and spores of sulfite-reducing clostridia). The three pre
      treatments were able to reduce the viscosity of the sludge, and this reduction
      was greater with increasing treatment intensity. However, only the alkali and
      thermal conditioning allowed the hygienization of the sludge, whereas the
      ultrasonication did not exhibit any notorious effect on microbial indicators
      populations. The selected optimum conditions were as follows: 27,000 kJ/kg TS for
      the ultrasound, 80  degrees C during 15 min for the thermal and 157 g NaOH/kg TS
      for the alkali. Afterward, the specific methane production was evaluated through
      biomethane potential tests at the specified optimum conditions. The alkali pre
      treatment exhibited the greatest methane production increase (34%) followed by
      the ultrasonication (13%), whereas the thermal pre-treatment presented a methane
      potential similar to the untreated sludge. Finally, an assessment of the
      different treatment scenarios was conducted considering the results together with
      an energy balance, which revealed that the ultrasound and alkali treatments
      entailed higher costs.

PMID- 24907481
TI  - Heat shock protein 27 is involved in PCV2 infection in PK-15 cells.
AB  - Porcine circovirus type 2 (PCV2) has been identified as the etiologic agent which
      causing postweaning multisystemic wasting syndrome in swine farms in the world.
      Some quantitative proteomic studies showed that many proteins significantly
      changed in PCV2-infected cells. To explore the role of cellular chaperones during
      PCV2 infection, cytoprotective chaperone Hsp27 was analyzed in PCV2-infected PK
      15 cells in this study. The results showed that Hsp27 could up-regulate and
      accumulate in phosphorylated forms in the nuclear zone during PCV2 replication.
      Suppression of Hsp27 phosphorylation with specific chemical inhibitors or
      downregulation of all forms of Hsp27 via RNA interference significantly reduced
      the virus replication. Meanwhile, over-expression of Hsp27 enhanced PCV2 genome
      replication and virion production. It indicated that Hsp27 was required for PCV2
      production in PK-15 cells culture. It should be helpful for understanding the
      mechanism of replication and pathogenesis of PCV2 and development of novel
      antiviral therapies in the future. 

PMID- 24907482
TI  - Retrospective on the all-in-one retroviral nucleocapsid protein.
AB  - This review aims at briefly presenting a retrospect on the retroviral
      nucleocapsid protein (NC), from an unspecific nucleic acid binding protein (NABP)
      to an all-in-one viral protein with multiple key functions in the early and late
      phases of the retrovirus replication cycle, notably reverse transcription of the
      genomic RNA and viral DNA integration into the host genome, and selection of the
      genomic RNA together with the initial steps of virus morphogenesis. In this
      context we will discuss the notion that NC protein has a flexible conformation
      and is thus a member of the growing family of intrinsically disordered proteins
      (IDPs) where disorder may account, at least in part, for its function as a
      nucleic acid (NA) chaperone and possibly as a protein chaperone vis-a-vis the
      viral DNA polymerase during reverse transcription. Lastly, we will briefly review
      the development of new anti-retroviral/AIDS compounds targeting HIV-1 NC because
      it represents an ideal target due to its multiple roles in the early and late
      phases of virus replication and its high degree of conservation. 

PMID- 24907484
TI  - Phase based venous suppression in resting-state BOLD GE-fMRI.
AB  - Resting-state functional MRI (RS-fMRI) is a widely used method for inferring
      connectivity between brain regions or nodes. As with task-based fMRI, the spatial
      specificity of the connectivity maps can be distorted by the strong biasing
      effect of the BOLD signal in macroscopic veins. In RS-fMRI this effect is
      exacerbated by the temporal coherences of physiological origin between large
      veins that are widely distributed in the brain. In gradient echo based EPI, used
      for the vast majority of RS-fMRI, macroscopic veins that carry BOLD-related
      changes exhibit a strong phase response. This allows for post-processing
      identification and removal of venous signals using a phase regressor technique.
      Here, we employ this approach to suppress macrovascular venous contributions in
      high-field whole-brain RS-fMRI data sets, resulting in significant changes to
      both the spatial localization of the networks and the correlations between the
      network nodes. These effects were observed at both the individual and group
      analysis level, suggesting that venous contamination is a confounding factor for
      RS-fMRI studies even at relatively low image resolutions. Suppression of the
      macrovascular signal using the phase regression approach may therefore help to
      better identify, delineate, and interpret the true structure of large-scale brain
      networks. 

PMID- 24907483
TI  - Microstructural differences in the thalamus and thalamic radiations in the
      congenitally deaf.
AB  - There is evidence of both crossmodal and intermodal plasticity in the deaf brain.
      Here, we investigated whether sub-cortical plasticity, specifically of the
      thalamus, contributed to this reorganisation. We contrasted diffusion weighted
      magnetic resonance imaging data from 13 congenitally deaf and 13 hearing
      participants, all of whom had learnt British Sign Language after 10 years of age.
      Connectivity based segmentation of the thalamus revealed changes to mean and
      radial diffusivity in occipital and frontal regions, which may be linked to
      enhanced peripheral visual acuity, and differences in how visual attention is
      deployed in the deaf group. Using probabilistic tractography, tracts were traced
      between the thalamus and its cortical targets, and microstructural measurements
      were extracted from these tracts. Group differences were found in microstructural
      measurements of occipital, frontal, somatosensory, motor and parietal thalamo
      cortical tracts. Our findings suggest that there is sub-cortical plasticity in
      the deaf brain, and that white matter alterations can be found throughout the
      deaf brain, rather than being restricted to, or focussed in the auditory cortex.

PMID- 24907485
TI  - Parietal and premotor cortices: activation reflects imitation accuracy during
      observation, delayed imitation and concurrent imitation.
AB  - This study investigated whether activation within areas belonging to the action
      observation and imitation network reveals a linear relation to the subsequent
      accuracy of imitating a bimanual rhythmic movement measured via a motion
      capturing system. 20 participants were scanned with functional magnetic resonance
      imaging (fMRI) when asked to imitate observed bimanual movements either
      concurrently versus with a delay (2s) or simply to observe the movements without
      imitation. Results showed that action observation relates to activation within
      classic mirror-related areas. Activation patterns were more widespread when
      participants were asked to imitate the movement. During observation with
      concurrent imitation, activation in the left inferior parietal lobe (IPL) was
      associated negatively with imitation accuracy. During observation in the delayed
      imitation condition, higher subsequent imitation accuracy was coupled with higher
      activation in the right superior parietal lobe (SPL) and the left parietal
      operculum (POp). During the delayed imitation itself, a negative association
      between imitation accuracy and brain activation was revealed in the right ventral
      premotor cortex (vPMC). We conclude that the IPL is involved in online comparison
      and visuospatial attention processes during imitation, the SPL provides a
      kinesthetic blueprint during movement observation, the POp preserves body
      identity, and the vPMC recruits motor representations--especially when no
      concurrent visual guidance is possible.

PMID- 24907486
TI  - Parenteral administration of attenuated Salmonella Typhimurium DeltaznuABC is
      protective against salmonellosis in piglets.
AB  - A major cause of salmonellosis in humans is the contamination of pork products.
      Infection in pigs can be controlled using bio-security programs, but they are not
      sufficient in countries where a high level of infection is recorded. In this
      context, the use of vaccines can represent a valid supplementary method of
      control. Recently, we have demonstrated that an attenuated strain of Salmonella
      enterica serovar Typhimurium (Salmonella Typhimurium DeltaznuABC) is protective
      against systemic and enteric salmonellosis in mouse and pig infection models,
      candidating this strain as an oral attenuated vaccine. In this study, we compared
      the efficacy of this attenuated Salmonella Typhimurium strain when administered
      orally or parenterally. Furthermore, in order to reproduce a pseudo-natural
      infection model, vaccinated pigs were allocated in the same pen with animals
      shedding virulent Salmonella Typhimurium. Animals were monitored weekly after
      vaccination and contact with infected piglets. Diarrhea and ataxia were recorded
      and Salmonella shedding was tested individually through bacterial culture. After
      four weeks of cohousing, piglets were euthanized, after which lymph nodes
      reactivity and gross lesions of the gut sections were scored at necropsy. Organs
      were submitted to microbiological and histological analyses. The data reported
      herein show that parenterally vaccinated animals do not shed the attenuated
      strain, and at the same time the absence of symptoms and decrease in virulent
      strain shedding in feces from day 6 after challenge demonstrated protection
      against infection induced by virulent Salmonella Typhimurium. In conclusion, our
      findings suggest that this is an alternative route of Salmonella Typhimurium
      DeltaznuABC administration, without ignoring the advantages associated with oral
      vaccination. 

PMID- 24907487
TI  - Vaccination in Southeast Asia--reducing meningitis, sepsis and pneumonia with new
      and existing vaccines.
AB  - Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria
      meningitidis are leading causes of vaccine-preventable diseases such as
      meningitis, sepsis and pneumonia. Although there has been much progress in the
      introduction of vaccines against these pathogens, access to vaccines remains
      elusive in some countries. This review highlights the current S. pneumoniae, H.
      influenzae type b, and N. meningitidis immunization schedules in the 10 countries
      belonging to the Association of Southeast Asian Nations (ASEAN). Epidemiologic
      studies may be useful for informing vaccine policy in these countries,
      particularly when determining the cost-effectiveness of introducing new vaccines.

PMID- 24907488
TI  - Clostridium difficile infection among immunocompromised patients in Rio de
      Janeiro, Brazil and detection of moxifloxacin resistance in a ribotype 014
      strain.
AB  - Clostridium difficile is a Gram-positive spore forming anaerobic bacterium, often
      associated with nosocomial diarrhea and pseudomembranous colitis. The acquisition
      of this organism occurs primarily in hospitals through accidental ingestion of
      spores, and its establishment and proliferation in the colon results from the
      removal of members of the normal intestinal flora during or after antibiotic
      therapy. In this study, stool samples from patients admitted to the University
      Hospital Clementino Fraga Filho (HUCCF/UFRJ) were screened for C. difficile
      toxins with an ELISA test and cultured with standard techniques for C. difficile
      isolation. A total of 74 stool samples were collected from patients undergoing
      antibiotic therapy between August 2009 and November 2010, only two (2.7%) were
      positive in the ELISA test and culture. A third isolate was obtained from a
      negative ELISA test sample. All cases of CDI were identified in patients with
      acute lymphoid or myeloid leukemia. Genotypic and phenotypic characterization
      showed that all strains carried toxins A and B genes, and belonged to PCR
      ribotypes 014, 043 and 046. The isolated strains were sensitive to metronidazole
      and vancomycin, and resistant to ciprofloxacin and levofloxacin. Resistance to
      moxifloxacin, was present in the strain from PCR-ribotype 014, that showed an
      amino acid substitution in gyrB gene (Asp 426 -> Asn). This is the first time
      that this mutation in a PCR-ribotype 014 strain has been described in Brazil. 

PMID- 24907489
TI  - Site-specific analysis of the O-glycosylation of bovine fetuin by electron
      transfer dissociation mass spectrometry.
AB  - Bovine fetuin often finds use as a test model for analytical methods, but the
      exact occupancy of its O-glycosylation sites has not yet been determined. An
      obstacle for a closer inspection of the five or six O-glycosylation sites is the
      close spacing of several sites on the same tryptic peptide. The advent of ion
      trap instruments with electron-transfer dissociation (ETD) capability and - for
      the type of instrument - high resolution prompted us to probe this technology for
      the investigation of the intricate posttranslational modifications O
      glycosylation and phosphorylation. Much information could be obtained by direct
      infusion ETD analysis of the fully sialylated tryptic 61-residue peptide
      harboring 8 hydroxyl amino acids of which four were indeed found to be, if only
      partially, glycosylated. The middle-down approach allowed recognizing an order of
      action of O-GalNAc transferase(s). No such hierarchy could be observed for
      phosphorylation. ETD fragmentation on an ion trap thus allowed in-depth analysis
      of a large, multiply O-glycosylated peptide, however, only by data accumulation
      over several minutes by direct infusion of a prefractionated sample. O
      glycosylation and phosphorylation sites re-defined and their occupancy including
      that of N-glycans were defined by this study. BIOLOGICAL SIGNIFICANCE: O
      glycosylation of natural or recombinant proteins poses a challenge because of the
      lack of unambiguous consensus sites, the agglomeration of several O-glycans in
      close proximity and the lack of efficient O-glycosidases. Even bovine fetuin, a
      frequently used test glycoprotein for glycosylation analysis, has hitherto not
      been fully characterized in terms of site occupancy. This gap shall hereby be
      closed by application of electron-transfer dissociation mass spectroscopy.

PMID- 24907490
TI  - Differential protein accumulations in isolates of the strawberry wilt pathogen
      Fusarium oxysporum f. sp. fragariae differing in virulence.
AB  - This study was conducted to define differences in Fusarium oxysporum f. sp.
      fragariae (Fof) isolates with different virulence efficiency to strawberry at the
      proteome level, in combination with their differences in mycelial growth,
      conidial production and germination. Comparative proteome analyses revealed
      substantial differences in mycelial proteomes between Fof isolates, where the 54
      differentially accumulated protein spots were consistently over-accumulated or
      exclusively in the highly virulent isolate. These protein spots were identified
      through MALDI-TOF/TOF mass spectrometry analyses, and the identified proteins
      were mainly related to primary and protein metabolism, antioxidation, electron
      transport, cell cycle and transcription based on their putative functions.
      Proteins of great potential as Fof virulence factors were those involved in
      ubiquitin/proteasome-mediated protein degradation and reactive oxygen species
      detoxification; the hydrolysis-related protein haloacid dehalogenase superfamily
      hydrolase; 3,4-dihydroxy-2-butanone 4-phosphate synthase associated with
      riboflavin biosynthesis; and those exclusive to the highly virulent isolate. In
      addition, post-translational modifications may also make an important
      contribution to Fof virulence. BIOLOGICAL SIGNIFICANCE: F. oxysporum f. sp.
      fragariae (Fof), the causal agent of Fusarium wilt in strawberry, is a serious
      threat to commercial strawberry production worldwide. However, factors and
      mechanisms contributing to Fof virulence remained unknown. This study provides
      knowledge of the molecular basis for the differential expression of virulence in
      Fof, allowing new possibilities towards developing alternative and more effective
      strategies to manage Fusarium wilt.

PMID- 24907492
TI  - Bidirectional links between Alzheimer's disease and Niemann-Pick type C disease.
AB  - Alzheimer's disease (AD) and Niemann-Pick type C (NPC) disease are progressive
      neurodegenerative diseases with very different epidemiology and etiology. AD is a
      common cause of dementia with a complex polyfactorial etiology, including both
      genetic and environmental risk factors, while NPC is a very rare autosomal
      recessive disease. However, the diseases share some disease-related molecular
      pathways, including abnormal cholesterol metabolism, and involvement of amyloid
      beta (Abeta) and tau pathology. Here we review recent studies on these
      pathological traits, focusing on studies of Abeta and tau pathology in NPC, and
      the importance of the NPC1 gene in AD. Further studies of similarities and
      differences between AD and NPC may be useful to increase the understanding of
      both these devastating neurological diseases. 

PMID- 24907491
TI  - MicroRNAs: a connection between cholesterol metabolism and neurodegeneration.
AB  - Dysregulation of cholesterol metabolism in the brain has been associated with
      many neurodegenerative disorders such as Alzheimer's disease, Niemann-Pick type C
      disease, Smith-Lemli-Opitz syndrome, Hungtington's disease and Parkinson's
      disease. Specifically, genes involved in cholesterol biosynthesis (24
      dehydrocholesterol reductase, DHCR24) and cholesterol efflux (ATP-binding cassete
      transporter, ABCA1, and apolipoprotein E, APOE) have been associated with
      developing Alzheimer's disease. Indeed, APOE was the first gene variation found
      to increase the risk of Alzheimer's disease and remains the risk gene with the
      greatest known impact. Mutations in another cholesterol biosynthetic gene, 7
      dehydrocholesterol reductase (DHCR7), cause Smith-Lemli-Opitz syndrome and
      impairment in cellular cholesterol trafficking caused by mutations in the NPC1
      protein results in Niemann-Pick type C disease. Taken together, these findings
      provide strong evidence that cholesterol metabolism needs to be controlled at
      very tight levels in the brain. Recent studies have implicated microRNAs (miRNAs)
      as novel regulators of cholesterol metabolism in several tissues. These small non
      coding RNAs regulate gene expression at the post-transcriptional level by either
      suppressing translation or inducing mRNA degradation. This review article focuses
      on how cholesterol homeostasis is regulated by miRNAs and their potential
      implication in several neurodegenerative disorders, such as Alzheimer's disease.
      Finally, we also discuss how antagonizing miRNA expression could be a potential
      therapy for treating cholesterol related diseases. 

PMID- 24907493
TI  - Mechanism underlying unaltered cortical inhibitory synaptic transmission in
      contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice.
AB  - Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with
      aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium
      channels. In FHM1 knockin mice, excitatory neurotransmission at cortical
      pyramidal cell synapses is enhanced, but inhibitory neurotransmission at
      connected pairs of fast-spiking (FS) interneurons and pyramidal cells is
      unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying
      the unaltered GABA release at cortical FS interneuron synapses remains unknown.
      Here, we show that the FHM1 R192Q mutation does not affect inhibitory
      transmission at autapses of cortical FS and other types of multipolar
      interneurons in microculture from R192Q knockin mice, and investigate the
      underlying mechanism. Lowering the extracellular [Ca(2+)] did not reveal gain-of
      function of evoked transmission neither in control nor after prolongation of the
      action potential (AP) with tetraethylammonium, indicating unaltered AP-evoked
      presynaptic calcium influx at inhibitory autapses in FHM1 KI mice. Neither
      saturation of the presynaptic calcium sensor nor short duration of the AP can
      explain the unaltered inhibitory transmission in the mutant mice. Recordings of
      the P/Q-type calcium current in multipolar interneurons in microculture revealed
      that the current density and the gating properties of the CaV2.1 channels
      expressed in these interneurons are barely affected by the FHM1 mutation, in
      contrast with the enhanced current density and left-shifted activation gating of
      mutant CaV2.1 channels in cortical pyramidal cells. Our findings suggest that
      expression of specific CaV2.1 channels differentially sensitive to modulation by
      FHM1 mutations in inhibitory and excitatory cortical neurons underlies the gain
      of-function of excitatory but unaltered inhibitory synaptic transmission and the
      likely consequent dysregulation of the cortical excitatory-inhibitory balance in
      FHM1. 

PMID- 24907494
TI  - Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by
      IgE.
AB  - BACKGROUND & AIMS: Eosinophilic esophagitis is usually triggered by foods, by
      unclear mechanisms. We evaluated the roles of IgE and IgG4 in the development of
      eosinophilic esophagitis. METHODS: We performed a prospective, randomized, double
      blind, placebo-controlled trial of adults with eosinophilic esophagitis given an
      antibody against IgE (omalizumab, n = 16) or placebo (n = 14) every 2-4 weeks for
      16 weeks, based on weight and serum level of IgE. Endoscopy was performed,
      esophageal biopsy specimens were collected, and symptoms were assessed at
      baseline and at 16 weeks. Maximum numbers of eosinophils/high-power field were
      determined. Homogenates of esophageal biopsy specimens from 11 subjects with
      eosinophilic esophagitis and 8 without (controls) were assessed for IgM, IgA, and
      IgG subclasses. In a retrospective analysis, we performed immunofluorescence
      analysis of IgG4 in fixed esophageal tissues from 2 patients with eosinophilic
      esophagitis who underwent esophagectomy and 47 consecutive autopsies (controls).
      We also performed immunofluorescence analysis of IgG4 in esophageal mucosal
      biopsy specimens from 24 subjects with eosinophilic esophagitis and 9 without
      (controls). Finally, sera were collected from 15 subjects with eosinophilic
      esophagitis and from 41 without (controls), and assayed for total and food
      reactive IgG4. RESULTS: Omalizumab did not alter symptoms of eosinophilic
      esophagitis or eosinophil counts in biopsy samples compared with placebo.
      Homogenates of esophageal tissues from patients with eosinophilic esophagitis had
      a 45-fold increase in IgG4 compared with controls (P < 3 * 10(-5)), but no
      significant increases in other IgG subclasses, IgM, or IgA. Sparse stromal
      deposits resembling immune complexes were found in 2 of 5 eosinophilic
      esophagitis biopsy specimens based on ultrastructural analysis. Esophagectomy
      samples from 2 patients with eosinophilic esophagitis contained 180 and 300 IgG4
      plasma cells/maximal high-power field, mainly in the deep lamina propria; these
      levels were greater than in tissues from controls. Fibrosis essentially was
      exclusive to the lamina propria. Granular extracellular IgG4 was detected in
      biopsy specimens from 21 of 24 patients with eosinophilic esophagitis, but in
      none of the specimens from 9 controls (P = 6 * 10(-6)). The total serum level of
      IgG4 increased only slightly in patients with eosinophilic esophagitis, compared
      with controls. Subjects with eosinophilic esophagitis had increased serum levels
      of IgG4 that reacted with milk, wheat, egg, and nuts-the 4 foods that most
      commonly trigger this condition (P <= 3 * 10(-4) for each food). CONCLUSIONS: In
      a prospective trial, omalizumab did not reduce symptoms of eosinophilic
      esophagitis or tissue eosinophil counts compared with placebo. This finding,
      along with observed granular deposits of IgG4, abundant IgG4-containing plasma
      cells, and serum levels of IgG4 reactive to specific foods, indicate that, in
      adults, eosinophilic esophagitis is IgG4-associated, and not an IgE-induced
      allergy. ClinicalTrials.gov number: NCT 00123630.

PMID- 24907495
TI  - Comparing stimulant effects in youth with ADHD symptoms and epilepsy.
AB  - To retrospectively examine response to stimulant treatment in patients with
      epilepsy and ADHD symptoms as predicted by seizure freedom for six months, use of
      methylphenidate (MPH) versus amphetamine (AMP) preparations, cognitive level, and
      medical records were searched for patients under the age of 18 with epilepsy and
      ADHD symptoms treated with MPH or AMP (n=36, age=10.4 +/- 3.5; male=67%).
      "Responders" had a CGI-improvement score of <= 2 and did not stop medication
      because of adverse effects. "Worsened" patients discontinued medication because
      of agitation/emotional lability. Seizure freedom did not predict treatment
      response. Lower cognitive level was associated with increased rate of worsening
      (p=0.048). No patients who were seizure-free at the start of the medication trial
      experienced an increase in seizures. Of the patients having seizures at the start
      of trial, one patient on MPH and two patients on AMP had increased seizures
      during the trial. Seizures returned to baseline frequency or less after stimulant
      discontinuation or anticonvulsant adjustment. Methylphenidate was associated with
      a higher response rate, with 12 of 19 given MPH (0.62 +/- 0.28 mg/kg/day)
      compared with 4 of 17 given AMP (0.37 +/- 0.26 mg/kg/day) responding (p=0.03).
      Methylphenidate treatment and higher cognitive level were associated with
      improved treatment outcome, while seizure freedom had no clear effect. Confidence
      in these findings is limited by the study's small, open-label, and uncontrolled
      design.

PMID- 24907496
TI  - Long-term postoperative atrophy of contralateral hippocampus and cognitive
      function in unilateral refractory MTLE with unilateral hippocampal sclerosis.
AB  - OBJECTIVE: This study aimed to evaluate long-term atrophy in contralateral
      hippocampal volume after surgery for unilateral MTLE, as well as the cognitive
      outcome for patients submitted to either selective transsylvian
      amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL).
      METHODS: We performed a longitudinal study of 47 patients with MRI signs of
      unilateral hippocampal sclerosis (23 patients with right-sided hippocampal
      sclerosis) who underwent surgical treatment for MTLE. They underwent
      preoperative/postoperative high-resolution MRI as well as neuropsychological
      assessment for memory and estimated IQ. To investigate possible changes in the
      contralateral hippocampus of patients, we included 28 controls who underwent two
      MRIs at long-term intervals. RESULTS: The volumetry using preoperative MRI showed
      significant hippocampal atrophy ipsilateral to the side of surgery when compared
      with controls (p<0.0001) but no differences in contralateral hippocampal volumes.
      The mean postoperative follow-up was 8.7 years (+/- 2.5 SD; median=8.0). Our
      patients were classified as Engel I (80%), Engel II (18.2%), and Engel III
      (1.8%). We observed a small but significant reduction in the contralateral
      hippocampus of patients but no volume changes in controls. Most of the patients
      presented small declines in both estimated IQ and memory, which were more
      pronounced in patients with left TLE and in those with persistent seizures.
      Different surgical approaches did not impose differences in seizure control or in
      cognitive outcome. CONCLUSIONS: We observed small declines in cognitive scores
      with most of these patients, which were worse in patients with left-sided
      resection and in those who continued to suffer from postoperative seizures. We
      also demonstrated that manual volumetry can reveal a reduction in volume in the
      contralateral hippocampus, although this change was mild and could not be
      detected by visual analysis. These new findings suggest that dynamic processes
      continue to act after the removal of the hippocampus, and further studies with
      larger groups may help in understanding the underlying mechanisms.

PMID- 24907497
TI  - Physiologic and cortical response to acute psychosocial stress in left temporal
      lobe epilepsy - a pilot cross-sectional fMRI study.
AB  - Stress is commonly reported as a seizure precipitant in individuals with poorly
      controlled seizures including temporal lobe epilepsy. The aim of the study was to
      assess the neural and physiologic correlates of psychosocial stress response
      during functional magnetic resonance imaging (fMRI) and their relationship with
      seizure occurrence in patients with left temporal lobe epilepsy (LTLE). We
      enrolled 23 patients with LTLE and 23 age- and sex-matched healthy controls
      (HCs); all underwent fMRI with control math task (CMT) and stress math task (SMT)
      and pre-/post-fMRI salivary cortisol analysis (acute stress reactivity calculated
      as % reduction from post-stress to recovery baseline; dCORT). The Beck Depression
      Inventory-II (BDI-II) and Perceived Stress Scale (PSS-10) were administered. T
      tests of performance and cortisol variables were performed. Processing and single
      subject modeling of fMRI response to CMT positive feedback and SMT negative
      feedback, group comparisons, and whole-brain correlation of seizure occurrence
      and fMRI response in patients with poorly controlled LTLE were performed.
      Patients with LTLE and healthy controls were similar in demographics, math
      performance, heart rate, and PSS-10 scores (all p>0.05). Patients with LTLE
      exhibited greater dCORT (p=0.048) and lower BDI-II scores (p=0.016) compared with
      HCs. Patients with poorly controlled LTLE showed a positive association between
      seizure frequency and dCORT (r=0.73, p=0.016). Functional MRI activation to
      feedback was similar between groups, including midfrontal, temporal, parietal,
      and occipital regions. Regression analyses revealed no group differences to
      positive feedback, but, compared with HCs, patients with LTLE showed decreased
      activation to negative feedback in the left cerebellum/middle occipital/fusiform
      gyri, left hippocampus/parahippocampus, bilateral medial
      frontal/cingulate/superior frontal gyri, right postcentral gyrus/inferior
      parietal lobule, and right insula/postcentral gyrus (p<0.05, corrected). Patients
      with poorly controlled LTLE showed negative association between seizure frequency
      and activation in the bilateral subgenual anterior cingulate (p<0.05, corrected).
      This study is the first to characterize the cortical and physiologic responses to
      acute psychosocial stress and to show a significant relationship between seizure
      control in LTLE and both the hypothalamic-pituitary-adrenal axis and fMRI signal
      reactivity to acute psychosocial stress. These findings extend our understanding
      of the complex interplay between stress, physiologic stress markers, and
      seizures/epilepsy. 

PMID- 24907498
TI  - The Epilepsy Pipeline Conference: accelerating hope.

PMID- 24907499
TI  - "I'm afraid I have bad news for you ...." Alcohol contributes to the occurrence
      of sudden unexpected death in epilepsy and years lost.

PMID- 24907500
TI  - Low likelihood of intracranial hemorrhage in patients with cirrhosis and altered
      mental status.
AB  - BACKGROUND & AIMS: Given the myriad causes of altered mental status (AMS),
      patients with cirrhosis and hepatic encephalopathy often present a diagnostic
      dilemma. In light of the perceived bleeding tendency of patients with cirrhosis,
      intracranial hemorrhage (ICH) is often feared, so these patients frequently
      undergo non-contrast computed tomography (CT) of the head. However, little is
      known about the diagnostic yield of CT for patients with cirrhosis presenting
      with AMS. METHODS: We analyzed all unique admissions of patients with cirrhosis
      who underwent head CT from 2003 through 2013 (N = 462) at the Beth Israel
      Deaconess Medical Center in Boston. By using blinded reviewers, we coded the
      indications and results of the CT scans separately and evaluated patient
      characteristics associated with acute findings. RESULTS: A higher proportion of
      patients who presented with falls or trauma, focal neurologic signs, or history
      of ICH were found to have ICH (13 of 146, 8.9%) than of patients who presented
      with AMS, headache, or fever (1 of 316, 0.3%; P < .0001). The odds ratio of ICH
      in patients with low-risk indications was 0.02 (95% confidence interval, 0.001
      0.14). The number needed to scan (NNS) for each positive result from CT varied by
      indication: focal neurologic deficits (NNS = 9), fall/trauma (NNS = 20), and AMS
      (NNS = 293). There was no association between presence of new, acute ICH and
      platelet count, international normalized ratio, level of creatinine, or Model for
      End-Stage Liver Disease score. CONCLUSIONS: Despite abnormal hemostatic indices,
      patients with cirrhosis presenting with AMS in the absence of focal neurologic
      deficits or trauma have a low likelihood of ICH.

PMID- 24907501
TI  - Pricing practices of gastroenterologists in New York.
AB  - There is growing awareness of the price disparities for equivalent services in
      healthcare. We aimed to characterize regional variations in fees charged by
      gastroenterologists in Manhattan, NY. All private practice gastroenterologists in
      Manhattan were contacted and asked what they charge fee-paying patients for
      initial consultations for nonspecific gastrointestinal symptoms. Cost information
      was obtained from 89 offices, and practices were classified on the basis of
      location in Manhattan. We observed significant regional variation;
      gastroenterologists on the Upper East Side (1.20-fold the overall mean) charged
      more than twice as those on the Upper West Side (0.58-fold the mean) and 50% more
      than gastroenterologists in South Manhattan (0.76-fold the mean). The coefficient
      of variation was 46%; the most expensive gastroenterologist charged 14-fold more
      than the least expensive. We provide evidence for significant regional variation
      in prices for medical services. Future studies are needed to characterize
      regional price variations in other aspects of healthcare. 

PMID- 24907502
TI  - Efficacy and safety of oral budesonide suspension in pediatric patients with
      eosinophilic esophagitis.
AB  - BACKGROUND & AIMS: No treatment has been approved by the U.S. Food and Drug
      Administration for eosinophilic esophagitis (EoE). We investigated the efficacy
      and safety of a new formulation of oral budesonide suspension (OBS), a
      corticosteroid, in a prospective, placebo-controlled, dose-ranging study.
      METHODS: Subjects 2-18 years old with symptoms of EoE and peak eosinophil counts
      >=20/high-power field at >=2 levels of the esophagus were randomly assigned to
      groups given placebo or low-dose, medium-dose, or high-dose OBS for 12 weeks.
      Doses and volumes were adjusted on the basis of patients' age to cover the entire
      esophagus. The primary efficacy end point was compound response to therapy (peak
      eosinophil counts <=6/high-power field at all levels of the esophagus and >=50%
      reduction in EoE symptom score). Multiple safety parameters were evaluated.
      RESULTS: Data from 71 subjects who completed all efficacy assessments were
      included in the primary efficacy analysis. At the end of 12 weeks, there were
      significantly greater percentages of responders in groups given medium-dose OBS
      (52.6%, P = .0092) and high-dose OBS (47.1%, P = .0174) than in the group given
      placebo (5.6%); there was no significant difference in percentages of responders
      between the low-dose OBS (11.8%) and placebo groups (P = .5282). The significant
      compound responses noted in the medium-dose and high-dose OBS groups were
      accounted for by the significant histologic responses; in contrast, all 4 groups
      (including the placebo group) had large symptom responses, and there was no
      significant difference in the percentage of subjects with a symptom response in
      either OBS group compared with the placebo group (P >= .1235). There were no
      unexpected safety concerns or signals. CONCLUSIONS: Peak eosinophil counts were
      significantly reduced throughout the esophagus in pediatric patients with EoE who
      were given medium-dose and high-dose OBS. There was a large symptom response to
      placebo that was similar to symptom responses in the OBS groups; symptom response
      did not distinguish OBS from placebo. ClinicalTrials.gov number, NCT00762073.

PMID- 24907503
TI  - Neighborhood level effects of socioeconomic status on liver transplant selection
      and recipient survival.
AB  - BACKGROUND & AIMS: Previous studies have reported that patients of higher
      socioeconomic status (SES) have increased access to liver transplantation and
      reduced waitlist mortality than patients of lower SES. However, little is known
      about the association between SES and outcomes after liver transplantation.
      METHODS: By using a link between the University HealthSystem Consortium and the
      Scientific Registry of Transplant Recipients databases, we identified 12,445
      patients who underwent liver transplantation from 2007 through 2011. We used a
      proportional hazards model to assess the effect of SES on patient survival,
      controlling for characteristics of recipients, donors, geography, and center.
      RESULTS: Compared with liver recipients in the lowest SES quintile, those in the
      highest quintile were more likely to be male, Caucasian, have private insurance,
      and undergo transplantation when they had lower Model for End-Stage Liver Disease
      scores. In proportional hazards model analysis, liver recipients of the lowest
      SES were at an increased risk for death within a median of 2 years after
      transplantation (hazard ratio, 1.17; 95% confidence interval, 1.02-1.35).
      CONCLUSIONS: Patients of lower SES appear to face barriers to liver
      transplantation, but perioperative outcomes (length of stay, in-hospital
      mortality, or 30-day readmission) do not differ significantly from those of
      patients of higher SES. However, fewer patients of low SES survive for 2 years
      after transplantation, independent of features of the recipient, donor, surgery
      center, or location.

PMID- 24907504
TI  - Naps are associated more commonly with gastroesophageal reflux, compared with
      nocturnal sleep.
AB  - BACKGROUND & AIMS: Acid reflux during nighttime sleep has been associated with
      more severe gastroesophageal reflux disease (GERD). Napping is common, especially
      after lunch time, in many cultures. We aimed to compare reflux characteristics
      between nighttime sleep and naps in patients with GERD. METHODS: We performed a
      study of 15 patients (mean age, 58.5 +/- 18.4 y; 10 men) with heartburn and/or
      regurgitation at least 3 times/week for the past 3 months, who experienced a nap
      in addition to regular nighttime sleep. All were evaluated using the demographics
      and GERD Symptoms Checklist questionnaires. Patients underwent pH testing
      concomitantly with actigraphy when they were not receiving antireflux treatment;
      only patients with abnormal results from pH tests were included in the study. Raw
      data from actigraphy analyses were superimposed over those collected from pH
      monitoring, matched by time. Integrative software was used to determine recumbent
      awake, recumbent-asleep, and naps alongside pH monitoring data. RESULTS: The mean
      duration of nocturnal sleep time and nap time were 446.0 +/- 100.7 minutes and
      61.9 +/- 51.8 minutes, respectively. The mean number of reflux events per hour
      was significantly greater during nap than nocturnal sleep time (40.1 +/- 69.9/h
      vs 3.5 +/- 4.2/h; P < .05). The mean duration of reflux events was longer during
      nap than nocturnal sleep time (1.9 +/- 2.8 min vs 1.5 +/- 2.7 min). The
      percentage of time spent at a pH less than 4 was significantly greater during
      naptime than nocturnal sleep time (36.2% +/- 38.8% vs 8.9% +/- 11.6%; P < .05).
      Arousals from naps were rare, compared with nocturnal sleep (mean, 0.7 +/- 1.1 vs
      4.2 +/- 2.9; P < .05). Patients also experienced more acid reflux associated with
      symptoms during nap than nocturnal sleep (mean, 8.08% vs 0.45%; P < .05).
      CONCLUSIONS: We associated naps with significantly greater numbers of, and
      duration of, esophageal acid exposure and symptoms, compared with nocturnal
      sleep. Naps therefore might have important effects on disease severity.

PMID- 24907505
TI  - Thiopurines and risk of colorectal neoplasia in patients with inflammatory bowel
      disease: a meta-analysis.
AB  - BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) are at
      increased risk for developing colorectal neoplasia. Researchers have debated
      whether treatment of IBD with thiopurines reduces cancer risk. We performed a
      meta-analysis of thiopurine exposure and risk of colorectal dysplasia or cancer
      in patients with IBD. METHODS: We used MEDLINE, EMBASE, and Cochrane search
      engines and abstract books from international conferences to identify relevant
      literature. We included studies on thiopurine exposure and risk of colorectal
      neoplasia in patients with ulcerative colitis or Crohn's disease. We calculated
      pooled odds ratios (ORs) with 95% confidence intervals (CIs) and performed a meta
      regression analysis of the effect of year of publication. Various sensitivity
      analyses were conducted. RESULTS: Fifteen studies fulfilled the inclusion
      criteria. Overall, we did not observe a significant effect of thiopurines on risk
      for colorectal neoplasia (dysplasia and/or cancer) in patients with IBD (OR,
      0.87; 95% CI, 0.71-1.06). The estimate did not change markedly in separate
      assessments of the 2 population-based studies (OR, 0.87; 95% CI, 0.59-1.29), the
      13 clinic-based studies (OR, 0.87; 95% CI, 0.59-1.09), the 7 cohort studies (OR,
      0.93; 95% CI, 0.67-1.28), or the 8 case-control studies (OR, 0.83; 95% CI, 0.65
      1.08). Studies that used neoplasia (dysplasia or cancer) as outcomes tended to
      show that thiopurines had protective effects (OR for neoplasia, 0.72; 95% CI,
      0.50-1.05); these effects were not observed in studies of colorectal cancer (OR,
      0.90; 95% CI, 0.72-1.12) or in studies published in recent years (meta
      regression; P = .16). CONCLUSIONS: In a meta-analysis, we did not find a
      significant protective effect of treatment with thiopurines on the risk of
      colorectal neoplasia in patients with IBD.

PMID- 24907506
TI  - Generic assay format for endo- and exonucleases based on fluorogenic substrates
      labeled with single fluorophores.
AB  - We previously described the development of fluorogenic assays for nucleic acid
      modifying enzymes based on synthetic oligonucleotides labeled with a single
      fluorophore. In the current work, we studied the performance of such singly
      labeled substrates as a function of the nucleotide sequence in the vicinity of
      the fluorophore and the nature of the fluorophore itself. In agreement with
      published studies, we found that a 3' end of the primer terminating in a dC
      residue opposite a 5' dG provides the greatest degree of fluorophore quenching.
      Adding a second dC residue at the 3' penultimate position opposite another dG
      increased the quenching further. Among the various dyes tested, the difluoro
      substituted fluorescein derivative Oregon Green emerged as a superior fluorophore
      for this assay format. We have now combined these findings into a new generic
      format for endonuclease assays. This format allows a substrate for any
      endonuclease to be obtained rapidly by simply replacing the enzyme's recognition
      sequence within the generic labeled molecule. Compared with our previous format,
      the new assays show greatly expanded signal dynamic ranges. The format is
      applicable to other nucleic acid-modifying enzymes such as exonucleases (e.g., T7
      gene 6 exonuclease) and DNA repair enzymes (e.g., uracil-DNA glycosylase). 

PMID- 24907507
TI  - Direct chemiluminescent enzyme immunoassay for atrial natriuretic peptide in
      mammalian plasma using a PEGylated antibody.
AB  - Atrial natriuretic peptide (ANP) is a peptide hormone that is synthesized and
      secreted by cardiac tissues and plays a pivotal role in maintaining
      cardiovascular homeostasis. Clinically, ANP is used as a marker of cardiovascular
      diseases, including heart failure. Although multiple ANP assays are currently
      available, a more sensitive assay is required for the direct measurement of
      plasma ANP where there is limited plasma availability, especially in mouse
      experiments. In the current study, we developed a plate-based sandwich
      chemiluminescent enzyme immunoassay for the measurement of plasma ANP in rats and
      mice without the need for prior extraction. To minimize nonspecific binding, we
      performed a single-step PEGylation procedure targeting the immobilized antibody,
      which markedly improved the assay's sensitivity and linearity. The linear range
      was 0.1 to 250 pM, and the minimum detection limit was 0.13 pM, 5-fold lower than
      the lowest value of the commercially available kits. ANP was directly measured in
      plasma samples without detectable cross-reactivity with B- and C-type natriuretic
      peptides. The accuracy of the assay was confirmed by spike recovery tests and
      dilution tests and by comparison with a conventional radioimmunoassay. Based on
      the species cross-reactivity, this assay can be used to measure human ANP.

PMID- 24907508
TI  - Multivariate analysis for resolving interactions of carbidopa with dsDNA at a
      fullerene-C60/GCE.
AB  - For the first time, interactions of carbidopa (CD) with double-stranded calf
      thymus DNA (dsDNA) in a phosphate buffered solution (PBS, 0.05M, pH=4.0) at a
      fullerene-C60/glassy carbon electrode (FLR/GCE) has been studied by cyclic
      voltammetry (CV), linear sweep voltammetry (LSV), and square wave voltammetry
      (SWV). The interaction of CD with dsDNA was also monitored using fluorescence (F)
      and UV-vis spectroscopic techniques. New information was obtained when a row- and
      column-wise augmented matrix consisting of SWV, LSV, F and UV-vis data was
      resolved using multivariate curve resolution-alternating least squares (MCR-ALS)
      as a powerful chemometric tool. Pure electrochemical and spectroscopic signals of
      CD, dsDNA and dsDNA-CD2 complex, and their concentration profiles were then
      successfully resolved. Molecular docking studies confirmed that the binding of CD
      with dsDNA shows minor groove binding mode which was in accordance with
      experimental results. Under optimized conditions, the SWV responses were linearly
      related to dsDNA concentration between 0.1 and 25.0nM and a limit of detection
      (LOD) of 0.03nM was calculated (3Sb/b=3). Moreover, the modified electrode
      exhibited long term stability, good repeatability, and reproducibility, and high
      sensitivity and selectivity toward dsDNA determination in human serum samples,
      demonstrating its feasibility toward dsDNA sensing. 

PMID- 24907509
TI  - N-glycan analysis of mannose/glucose specific lectin from Dolichos lablab seeds.
AB  - An affinity purified mannose/glucose specific lectin from the seeds of Dolichos
      lablab (Indian bean/lablab bean) resolves into five subunits upon SDS-PAGE in the
      range of Mr 12-20kDa. Partial de novo sequencing of subunits resulted in 88% and
      73% sequence coverage for alpha and beta subunits of the cDNA derived FRIL (Flt3
      receptor interacting lectin) sequence, respectively and suggested that four bands
      correspond to the alpha-subunits while the band of lowest molecular mass is
      designated as beta. It was proposed in an earlier study on FRIL that the
      difference in molecular mass of alpha-subunits is due to differences in C
      terminal processing and differential N-glycosylation i.e. numbers of N-glycans
      present (Colucci et al., 1999). Thus, differential N-glycosylation of the
      purified mannose/glucose specific lectin was unravelled by in-gel
      trypsin/chymotrypsin digestion of the alpha-subunits followed by desalting and
      ZIC-HILIC enrichment of N-glycopeptides. Subsequently, analyses by nano
      electrospray ionisation quadrupole time of flight mass spectrometry and low
      energy collision-induced dissociation experiments revealed the presence of a
      typical paucimannose type N-glycan (Man2(Xyl)GlcNAc2(Fuc)) in alpha subunits 2-4.

PMID- 24907510
TI  - Mycobacterial 3-hydroxyacyl-l-thioester dehydratase Y derived from Mycobacterium
      tuberculosis induces COX-2 expression in mouse macrophages through MAPK-NF-kappaB
      pathway.
AB  - Tuberculosis (TB) is a leading cause of global mortality due to infectious
      diseases. Expression of cyclooxygenase-2 (COX-2) acts as an important influencing
      factor favoring bacillary survival during TB infection. In this study, we
      investigated the Mycobacterium tuberculosis proteins recognized by sera from TB
      patient collected before and after anti-TB therapy by dynamic immunoproteomics
      and identified a novel immune-regulating protein 3-hydroxyacyl-l-thioester
      dehydratase Y (HtdY), which could induce COX-2 expression in mouse macrophages.
      Signaling perturbation data showed that the activation of p38, ERK 1/2 and JNK
      1/2 MAPK as well as NF-kappaB played critical role in this immune response. Taken
      together, our findings indicated that mycobacterial HtdY might contribute to the
      persistence of the TB infection by inducing COX-2 expression through MAPK-NF
      kappaB signaling pathway. 

PMID- 24907511
TI  - Cleaning up blood samples using a modified "QuEChERS" procedure for the
      determination of drugs of abuse and benzodiazepines by UPLC-MSMS(?).
AB  - The "QuEChERS" (quick, easy, cheap, effective, rugged, and safe) dispersive SPE
      (dSPE) method is an emerging sample preparation technique that is becoming
      increasingly popular in the area of multi-residue pesticide analysis in food and
      agricultural products. A simplified QuEChERS extraction method followed by ultra
      high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has
      been developed for the simultaneous determination of forensically relevant drugs
      of abuse (opiates including buprenorphine, methadone and fentanyl and analogues,
      cocaine and metabolites, amphetamines, LSD) and benzodiazepines and analogues (Z
      drugs) in 1mL of human whole blood performing a sole extraction. The method was
      validated showing good repeatability, accuracy and linearity; LODs were 0.5ng/mL
      for all benzodiazepines tested while for drugs of abuse LODs varied from 0.05 to
      2ng/mL. The method showed high throughput capabilities and was applied on various
      forensic cases for determination of pharmaceuticals and drugs of abuse. 

PMID- 24907512
TI  - Dual role of cerebral blood flow in regional brain temperature control in the
      healthy newborn infant.
AB  - Small shifts in brain temperature after hypoxia-ischaemia affect cell viability.
      The main determinants of brain temperature are cerebral metabolism, which
      contributes to local heat production, and brain perfusion, which removes heat.
      However, few studies have addressed the effect of cerebral metabolism and
      perfusion on regional brain temperature in human neonates because of the lack of
      non-invasive cot-side monitors. This study aimed (i) to determine non-invasive
      monitoring tools of cerebral metabolism and perfusion by combining near-infrared
      spectroscopy and echocardiography, and (ii) to investigate the dependence of
      brain temperature on cerebral metabolism and perfusion in unsedated newborn
      infants. Thirty-two healthy newborn infants were recruited. They were studied
      with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux
      tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using
      superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue
      oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic
      rate of oxygen relative to rSVC flow (CMRO2 index) were also estimated. A greater
      rSVC flow was positively associated with higher brain temperatures, particularly
      for superficial structures. The CMRO2 index and rSVC flow were positively
      coupled. However, brain temperature was independent of FOE and the CMRO2 index. A
      cooler ambient temperature was associated with a greater temperature gradient
      between the scalp surface and the body core. Cerebral oxygen metabolism and
      perfusion were monitored in newborn infants without using tracers. In these
      healthy newborn infants, cerebral perfusion and ambient temperature were
      significant independent variables of brain temperature. CBF has primarily been
      associated with heat removal from the brain. However, our results suggest that
      CBF is likely to deliver heat specifically to the superficial brain. Further
      studies are required to assess the effect of cerebral metabolism and perfusion on
      regional brain temperature in low-cardiac output conditions, fever, and with
      therapeutic hypothermia.

PMID- 24907513
TI  - Signaling mechanisms regulating Wallerian degeneration.
AB  - Wallerian degeneration (WD) occurs after an axon is cut or crushed and entails
      the disintegration and clearance of the severed axon distal to the injury site.
      WD was initially thought to result from the passive wasting away of the distal
      axonal fragment, presumably because it lacked a nutrient supply from the cell
      body. The discovery of the slow Wallerian degeneration (Wld(s)) mutant mouse, in
      which distal severed axons survive intact for weeks rather than only one to two
      days, radically changed our thoughts on the autonomy of axon survival. Wld(s)
      taught us that under some conditions the axonal compartment can survive for weeks
      after axotomy without a cell body. The phenotypic and molecular characterization
      of Wld(S) and current models for Wld(S) molecular function are reviewed herein
      the mechanism(s) by which Wld(S) spares severed axons remains unresolved.
      However, recent studies inspired by Wld(s) have led to the identification of the
      first 'axon death' signaling molecules whose endogenous activities promote axon
      destruction during WD. 

PMID- 24907514
TI  - Recombinant human tyrosyl-tRNA synthetase, a novel thrombopoietic agent.
AB  - Chemo- and radiotherapy induced thrombocytopenia present significant limitations
      for tumor therapy. In this study, we examined the therapeutic effect of
      recombinant human tyrosyl-tRNA synthetase (rhTyrRS) against development of
      thrombocytopenia in cyclophosphamide (CTX) treated mice. Our data indicate that
      intraperitoneal administration of at least 10 MUg/day rhTyrRS for 7 days
      significantly prevents the decrease in platelets 8 days after CTX injection. The
      data further demonstrate that rhTyrRS promotes migration and aggregation of
      megakaryocytes to the bone marrow niche. Real-time PCR and flow cytometry reveal
      that VCAM-1 is particularly important for the adhesion. Together, these data
      suggest that rhTyrRS might be a useful therapeutic agent for chemotherapy-induced
      thrombocytopenia.

PMID- 24907516
TI  - Desmin and nerve terminal expression during embryonic development of the lateral
      pterygoid muscle in mice.
AB  - OBJECTIVE: In adults, the lateral pterygoid muscle (LPM) is usually divided into
      the upper and lower head, between which the buccal nerve passes. Recent
      investigations have demonstrated foetal developmental changes in the
      topographical relationship between the human LPM and buccal nerve. However, as
      few studies have investigated this issue, we clarified the expression of desmin
      and nerve terminal distribution during embryonic development of the LPM in mice.
      METHODS: We utilized immunohistochemical staining and reverse transcription chain
      reaction (RT-PCR) to clarify the expression of desmin and nerve terminal
      distribution. RESULTS: We observed weak expression of desmin in the LPM at
      embryonic day (ED) 11, followed by an increase in expression from embryonic days
      12-15. In addition, starting at ED 12, we observed preferential accumulation of
      desmin in the vicinity of the myotendinous junction, a trend that did not change
      up to ED 15. Nerve terminal first appeared at ED 13 and formed regularly spaced
      linear arrays at the centre of the muscle fibre by ED 15. The results of
      immunohistochemical staining agreed with those of RT-PCR analysis. CONCLUSION: We
      found that desmin accumulated in the vicinity of the myotendinous junction
      starting at ED 12, prior to the onset of jaw movement. We speculate that the
      accumulation of desmin is due to factors other than mechanical stress experienced
      during early muscle contraction. Meanwhile, the time point at which nerve
      terminals first appeared roughly coincided with the onset of jaw movement.

PMID- 24907515
TI  - Propofol selectively alters GluA1 AMPA receptor phosphorylation in the
      hippocampus but not prefrontal cortex in young and aged mice.
AB  - Propofol is a commonly used general anesthetic agent which has been previously
      shown to enhance the inhibitory GABAergic transmission in the central nervous
      system. In addition to the GABAergic element, the excitatory transmission may be
      another central molecular site impacted by propofol. Increasing evidence implies
      that the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor
      represents an excitatory amino acid receptor subtype subjected to the regulation
      by propofol. Indeed, in this study, we found that a single injection of propofol
      at an anesthetic dose increased AMPA receptor GluA1 subunit phosphorylation in
      young (2-3 months old) and aged (20-21 months old) mice in vivo. Propofol caused
      an increase in GluA1 phosphorylation in the hippocampus but not in the prefrontal
      cortex. The propofol effect was also site-selective as the drug elevated GluA1
      phosphorylation at serine 831 (S831) but not serine 845. Interestingly, while
      propofol induced a moderate and transient increase in S831 phosphorylation in
      young mice, the drug caused a substantial and sustained S831 phosphorylation in
      aged animals. Total GluA1 abundance remained stable in the hippocampus and
      prefrontal cortex in both young and aged mice in response to propofol. These
      results provide evidence supporting the sensitivity of GluA1 AMPA receptors to
      propofol. A single dose of propofol was able to upregulate GluA1 phosphorylation
      in the confined hippocampus in an age-dependent manner. 

PMID- 24907517
TI  - Aliphatic fatty acids and esters: inhibition of growth and exoenzyme production
      of Candida, and their cytotoxicity in vitro: anti-Candida effect and cytotoxicity
      of fatty acids and esters.
AB  - The secretion of extracellular phospholipases and proteinases of Candida has been
      described as a relevant virulence factor in human infections. Aliphatic fatty
      acids have antimicrobial properties, but the mechanism by which they affect the
      virulence factors of microorganisms, such as Candida, is still unclear, and there
      are a few reports about their toxicity. The current study investigated the in
      vitro antifungal activity, exoenzyme production and cytotoxicity of some
      aliphatic fatty acids and their ester derivatives against the Candida species.
      The minimum inhibitory concentration and minimum fungicidal concentrations of
      aliphatic medium-chain fatty acids, methyl and ethyl esters were performed using
      the CLSI M27-A3 method and the cytotoxicity assay was performed according to ISO
      10993-5. The influence of these compounds in the inhibition of the production of
      hydrolytic enzymes, phospholipases and proteinases by Candida was also
      investigated. Data analysis was performed using the one-way ANOVA method
      (p<=0.05). In relation to the MIC against Candida species, the fatty acid with
      the best result was Lauric acid, although its ester derivatives showed no
      activity. The inhibition of phospholipase production was more significant than
      the inhibition of proteinase production by Candida. Tested fatty acids revealed
      more than 80% cell viability in their MIC concentrations. Additionally, a cell
      viability of 100% was reported at concentrations of anti-enzymatic effect.
      Therefore, the potential use of these fatty acids could be the basis for more
      antimicrobial tests. 

PMID- 24907518
TI  - Antiadherent activity of Schinus terebinthifolius and Croton urucurana extracts
      on in vitro biofilm formation of Candida albicans and Streptococcus mutans.
AB  - OBJECTIVE: To evaluate the antiadherent property of crude, methanol and acetate
      methanol extract fractions from Schinus terebinthifolius and Croton urucurana in
      hydroalcoholic (HA) and dimethylsulfoxide (DMSO) solvents on in vitro biofilms
      formed by Streptococcus mutans and Candida albicans strains. DESIGN: The minimal
      concentration of adherence (MICA) was determined to evaluate the antiadherent
      potential of extracts on the in vitro biofilm formation. The extracts of plants
      were subjected to thin layer chromatography (TLC) in order to detect what class
      of compounds was responsible for the antiadherent activity. Data were estimated
      by analysis of variance (ANOVA) complemented by Tukey test level of significance
      set at 5%. RESULTS: Both plants demonstrated inhibition of S. mutans and C.
      albicans on in vitro biofilm formation. The biofilms of C. albicans were more
      efficiently inhibited by the S. terebinthifolius fraction of acetate-methanol and
      methanol in hydroalcoholic solvents (p<0.05). The S. mutans biofilms adherence
      was best inhibited by the S. terebinthifolius crude extract and its methanolic
      fraction, both in hydroalcoholic solvent (p<0.05). TLC of crude extracts and
      fractions of S. terebinthifolius detected the presence of several active
      compounds, including phenolic compounds, anthraquinones, terpenoids, and
      alkaloids. C. urucurana extracts confirmed activity for both microorganisms
      (p<0.05). However, higher concentrations were needed to achieve antiadherent
      activity, mainly to inhibit in vitro biofilm formation of C. albicans.
      CONCLUSION: The antiadherent potential of both plants on in vitro biofilms formed
      by C. albicans and S. mutans were confirmed, suggesting the importance of studies
      about these extracts for therapeutic prevention of oral diseases associated with
      oral biofilms.

PMID- 24907520
TI  - Studies of the chronological course of third molars eruption in a northern
      Chinese population.
AB  - Dental age estimation is of great importance for individual identification in
      forensic medicine and many other fields of study. Among them, tooth eruption is a
      parameter developmental morphology that can be determined by clinical
      examinations or by dental X-rays. The purpose of present research is to study the
      chronological course of third molars eruption in a Chinese population and compare
      that with other ethnic population for age estimation. A total of 1135
      conventional orthopantomograms from 506 male and 629 female northern Chinese
      subjects aged between 11 and 26 years were analyzed. The eruption status of the
      third molars was assessed using the developmental stages described by Olze et al.
      Results showed that the third molars 18, 28, 38 and 48 in the stage A showed
      significant younger average age in males than in females. The Olze's stage A
      could be used as a reference stage to determine whether a male or female northern
      Chinese is likely to be equal or above age 16, with 99.6-100% and 97.4-98.1% of
      correct predictions, respectively. The stage D was found to be a useful marker
      for diagnosing age under 16 years, with 98.9-100% and 100% of correct predictions
      in males and females, respectively. There were some significant differences of
      the chronological course of the third molars eruption in different ethnic groups,
      which indicated that population-specific standards could enhance the accuracy of
      forensic age estimation based on third molar eruption. 

PMID- 24907519
TI  - IL-17 inhibits osteoblast differentiation and bone regeneration in rat.
AB  - OBJECTIVE: The interleukin-17 (IL-17) family is a group of pro-inflammatory
      cytokines that are produced by a subset of helper T cells. IL-17 family members
      are not only involved in the immune response of tissues but also play a role in
      bone metabolism. Although the role of IL-17 in osteoclast-mediated bone
      resorption has been extensively studied, its role during osteoblast-mediated bone
      formation has rarely been investigated. In this study, we examined the effect of
      IL-17 on osteogenesis in rats both in vitro and in vivo. DESIGN: To evaluate
      osteogenesis in vitro, rat calvarial osteoblast precursor cells were cultured for
      14 days in osteogenic medium with or without 50ng/mL IL-17. Osteogenic activity
      was evaluated by alkaline phosphatase and alizarin red staining. The mRNA
      expression of alkaline phosphatase, osteocalcin, and osterix was also measured by
      using real-time PCR. To test whether IL-17 affects bone formation in vivo, bone
      filling was examined by micro-computed tomography and histological observations
      at 8 weeks after critical-sized defects were made in rat calvaria. RESULTS: The
      presence of IL-17 significantly reduced alkaline phosphatase and alizarin red
      staining and the expression of alkaline phosphatase, osteocalcin, and osterix in
      vitro. IL-17 also significantly inhibited the filling of calvarial defects in
      vivo. CONCLUSION: IL-17 exerted a negative effect on osteogenesis in a rat model.
      In contrast to the previously reported beneficial effect on osteogenic
      differentiation of human mesenchymal stem cells, our results suggest a species or
      cell type-specific role for IL-17 in bone formation.

PMID- 24907521
TI  - Effects of PEMF exposure at different pulses on osteogenesis of MC3T3-E1 cells.
AB  - OBJECTIVE: Pulsed electromagnetic fields (PEMFs) were considered to be a factor
      which may affect osteogenesis of osteoblasts, but the effects were diverse with
      different PEMF parameters. The aim of the current study is to explore the effects
      of exposure to PEMFs at different pulse number on osteogenesis of osteoblasts.
      DESIGN: The mouse osteoblast-like MC3T3-E1 cells were exposed to 0, 400 or 2800
      pulses 400kV/m PEMF and the proliferation, differentiation and mineralization of
      cells were observed after PEMF exposure by the methods of MTT, biochemical
      measurement, real-time PCR and Alizarin Red assay. RESULTS: Compared with 0
      pulses groups, the growth curve, alkaline phosphatase (ALP) activity, mRNA level
      of osteocalcin (OCN) and mineralized nodule formation of MC3T3-E1 cells did not
      change after 400 pulses PEMF exposure, but decreased after 2800 pulses PEMF
      exposure. It suggested that under our experimental conditions, only 2800 pulses
      400kV/m PEMF exposure can suppress the proliferation, differentiation and
      mineralization of MC3T3-E1 cells, but 400 pulses 400kV/m PEMF exposure cannot.
      CONCLUSIONS: Pulse number is another involved parameter which may influence the
      effects of PEMF on osteogenesis of osteoblasts.

PMID- 24907522
TI  - Effect of the secretory leucocyte proteinase inhibitor (SLPI) on Candida albicans
      biological processes: a therapeutic alternative?
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of SLPI on the
      growth and biological processes of Candida albicans. METHODS: Two C. albicans
      strains were used in this study, a clinical isolate resistant to fluconazole
      (PRI) and a reference strain ATCC 24433. The minimal inhibitory concentration
      (MIC) was determined according to the CLSI methodology. The influence of SLPI on
      secreted serine proteinase activities (SSP) was measured by the cleavage of
      specific substrate, and surface hydrophobicity was determined by the aqueous
      hydrocarbon biphasic separation method. Flow cytometry was performed to
      investigate receptors for SLPI and variations in the cell wall mannoprotein
      expression. Interaction between yeast and epithelium was assessed using the MA
      104 cells lineage. Ultrastructure was analyzed by transmission electron
      microscopy (TEM). RESULTS: MIC values were calculated as 18 and 18.9MUM for the
      PRI and ATCC 24433, respectively. SSP activity was reduced by 48.8% by 18MUM of
      SLPI and cell surface hydrophobicity increased by 11.1%. Flow cytometry suggest
      the existence of SLPI binding sites on the surface of the yeast. Results showed a
      reduction in the expression of mannoproteins in 20.8% by the cells treated with
      80MUM of SLPI, and 18MUM reduced the adhesion of yeasts to mammalian cells in
      60.1%. TEM revealed ultrastructural changes in cells treated with 80MUM of SLPI,
      such as the presence of membrane-like structures within the cytoplasm.
      CONCLUSIONS: SLPI exerts a significant influence on C. albicans viability and
      biological processes. Considering its constitutive and physiologic features, SLPI
      may become a promising tool for the development of new methodologies for the
      treatment and control of candidiasis.

PMID- 24907523
TI  - Climatic seasonality may affect ecological network structure: food webs and
      mutualistic networks.
AB  - Ecological networks exhibit non-random structural patterns, such as modularity
      and nestedness, which determine ecosystem stability with species diversity and
      connectance. Such structure-stability relationships are well known. However,
      another important perspective is less well understood: the relationship between
      the environment and structure. Inspired by theoretical studies that suggest that
      network structure can change due to environmental variability, we collected data
      on a number of empirical food webs and mutualistic networks and evaluated the
      effect of climatic seasonality on ecological network structure. As expected, we
      found that climatic seasonality affects ecological network structure. In
      particular, an increase in modularity due to climatic seasonality was observed in
      food webs; however, it is debatable whether this occurs in mutualistic networks.
      Interestingly, the type of climatic seasonality that affects network structure
      differs with ecosystem type. Rainfall and temperature seasonality influence
      freshwater food webs and mutualistic networks, respectively; food webs are
      smaller, and more modular, with increasing rainfall seasonality. Mutualistic
      networks exhibit a higher diversity (particularly of animals) with increasing
      temperature seasonality. These results confirm the theoretical prediction that
      the stability increases with greater perturbation. Although these results are
      still debatable because of several limitations in the data analysis, they may
      enhance our understanding of environment-structure relationships. 

PMID- 24907524
TI  - Beneficial rhizobacteria from rice rhizosphere confers high protection against
      biotic and abiotic stress inducing systemic resistance in rice seedlings.
AB  - The present study reports a screening for PGPR in a highly selective environment,
      the rhizosphere of rice plants, in southwestern of Spain. Among the 900 isolates,
      only 38% were positive for at least one of the biochemical activities to detect
      putative PGPR. The best 80 isolates were selected and identified by 16S rRNA
      partial sequencing. Among these, 13 strains were selected for growth promotion
      assays. Only one strain (BaC1-38) was able to significantly increase height,
      while nine strains significantly inhibited it. Five strains significantly
      increased dry weight, and only BaC1-21 significantly decreased it. Based on
      significant modifications in growth, three bacteria (BaC1-13, BaC1-21 and BaC1
      38) were tested for systemic induction of resistance against stress challenge
      (salt and Xanthomonas campestris infection). Protection against salt stress and
      pathogen infection was similar; BaC1-38 protected by 80%, BaC1-13 by 50% and BaC1
      21 only by 20%. Toxicity of salt stress to the plants was evaluated by
      photosynthetic efficiency of seedlings. Fv/Fm only decreased significantly in
      plants inoculated with BaC1-13. PhiPSII also decreased significantly in plants
      inoculated with BaC1-21, but increased significantly with BaC1-38. NPQ decreased
      significantly in plants inoculated with BaC1-21. The two strains able to induce
      systemic resistance against Xanthomonas campestris seem to work by different
      pathways. BaC1-13 primed enzymes related with the detoxification of reactive
      oxygen species (ROS). However, BaC1-38 primed pathogenesis-related proteins
      (PRs), and this pathway was more effective, both improved chlorophyll index
      confirming the priming state of the plant. 

PMID- 24907525
TI  - Wound healing response and xylem differentiation in tobacco plants over
      expressing a fungal endopolygalacturonase is mediated by copper amine oxidase
      activity.
AB  - In this work, we have investigated the involvement of copper amine oxidase (CuAO;
      EC 1.4.3.21) in wound healing and xylem differentiation of Nicotiana tabacum
      plants over-expressing a fungal endopolygalacturonase (PG plants), which show
      constitutively activated defence responses. In petioles and stems of PG plants,
      we found higher CuAO activity and lower polyamine (PA) levels, particularly
      putrescine (Put), with respect to wild-type (WT) plants. Upon wounding, a more
      intense autofluorescence of cell wall phenolics was observed in correspondence of
      wound surface, extending to epidermis and cortical parenchima only in PG plants.
      This response was mostly dependent on CuAO activity, as suggested by the
      reversion of autofluorescence upon supply of 2-bromoethylamine (2-BrEt), a CuAO
      specific inhibitor. Moreover, in unwounded plants, histochemical analysis
      revealed a tissue-specific expression of the enzyme in the vascular cambium and
      neighboring derivative cells of both petioles and stems of PG plants, whereas the
      corresponding WT tissues appeared unstained or faintly stained. A higher
      histochemical CuAO activity was also observed in xylem cells of PG plants as
      compared to WT xylem tissues suggesting a peculiar role of CuAO activity in xylem
      differentiation in PG plants. Indeed, roots of PG plants exhibited early xylem
      differentiation, a phenotype consistent with both the higher CuAO and the lower
      Put levels observed and supported by the 2-BrEt-mediated reversion of early root
      xylem differentiation and H2O2 accumulation. These results strongly support the
      relevance of PA-catabolism derived H2O2 in defence responses, such as those
      signaled by a compromised status of cell wall pectin integrity. 

PMID- 24907526
TI  - Different mechanisms drive the performance of native and invasive woody species
      in response to leaf phosphorus supply during periods of drought stress and
      recovery.
AB  - The effects of drought stress and leaf phosphorus (Pi) supply on photosynthetic
      metabolism in woody tropical species are not known, and given the recent global
      environmental change models that forecast lower precipitation rates and periods
      of prolonged drought in tropical areas, this type of study is increasingly
      important. The effects of controlled drought stress and Pi supply on potted young
      plants of two woody species, Anadenanthera colubrina (native) and Prosopis
      juliflora (invasive), were determined by analyzing leaf photosynthetic
      metabolism, biochemical properties and water potential. In the maximum stress,
      both species showed higher leaf water potential (Psil) in the treatment drought
      +Pi when compared with the respective control -Pi. The native species showed
      higher gas exchange under drought +Pi than under drought -Pi conditions, while
      the invasive species showed the same values between drought +Pi and -Pi. Drought
      affected the photochemical part of photosynthetic machinery more in the invasive
      species than in the native species. The invasive species showed higher leaf amino
      acid content and a lower leaf total protein content in both Pi treatments with
      drought. The two species showed different responses to the leaf Pi supply under
      water stress for several variables measured. In addition, the strong resilience
      of leaf gas exchange in the invasive species compared to the native species
      during the recovery period may be the result of higher efficiency of Pi use. The
      implications of this behavior for the success of this invasive species in
      semiarid environments are discussed. 

PMID- 24907527
TI  - Reactive oxygen species burst induced by aluminum stress triggers mitochondria
      dependent programmed cell death in peanut root tip cells.
AB  - Recent studies had certified that aluminum (Al) induced ROS production and
      programmed cell death (PCD) in higher plants. The relationship between ROS
      production and PCD occurrence under Al stress is uncovered. The results showed
      that root elongation inhibition and PCD occurrence was induced by 100 MUM AlCl3.
      Al stress induced ROS burst, up-regulated Rboh and COX gene expression, increased
      mitochondrial permeability transition pore (MPTP) opening, decreased inner
      mitochondrial membrane potential (DeltaPsim), released cytochrome c from
      mitochondria to cytoplasm, activated caspase 3-like protease activity. Exogenous
      H2O2 aggravated the changes caused by Al and accelerated PCD occurrence, but ROS
      scavenger CAT and AsA reversed the changes caused by Al and inhibited PCD
      production. A potential cascade of cellular events during Al induced PCD via
      mitochondria dependent pathway and the mechanism of ROS on regulating PCD induced
      by Al is proposed. 

PMID- 24907528
TI  - Engineering anthocyanin biosynthesis in plants.
AB  - Anthocyanins are water-soluble pigments giving the red, purple and blue colours
      of many flowers and fruit. In addition to their physiological roles in plants, to
      attract pollinators and seed dispersers, dietary anthocyanins are associated with
      protection against certain cancers, cardiovascular diseases and other chronic
      human disorders. Enhanced supplies of pure anthocyanins would service the demands
      of research to investigate these health-promoting effects and would also prove a
      valuable resource for the colourants and cosmetic industries to investigate the
      effects of chemical modifications, co-pigments, and pH on colour and stability
      for developing new plant sources of natural colourants, and new natural colours. 

PMID- 24907529
TI  - Dosage, duplication, and diploidization: clarifying the interplay of multiple
      models for duplicate gene evolution over time.
AB  - Requirements to maintain dosage balance shape many genome-scale patterns in
      organisms, including the resolution of whole genome duplications (WGD), as well
      as the varied effects of aneuploidy, segmental duplications, tandem duplications,
      gene copy number variations (CNV), and epigenetic marks. Like
      neofunctionalization and subfunctionalization, the impact of absolute and
      relative dosage varies over time. These variations are of particular importance
      in understanding the role of dosage in the evolution of polyploid organisms.
      Numerous investigations have found the consequences of polyploidy remain distinct
      from small-scale duplications (SSD). This observation is significant as all
      flowering plants have experienced at least two ancient polyploid events, and many
      angiosperm lineages have undergone additional rounds of polyploidy. Intriguingly,
      recent studies indicate a link between how epigenetic marks in recent
      allopolyploids may induce immediate changes in gene expression and the longer
      term patterns of biased fractionation and chromosomal evolution. We argue that
      dosage effects represent one aspect of an emerging pluralistic framework, a
      framework that will use biophysics, genomic technologies, and systems-level
      models of cells to broaden our view of how genomes evolve. 

PMID- 24907530
TI  - Principles and applications of TAL effectors for plant physiology and metabolism.
AB  - Recent advances in DNA targeting allow unprecedented control over gene function
      and expression. Targeting based on TAL effectors is arguably the most promising
      for systems biology and metabolic engineering. Multiple, orthogonal TAL-effector
      reagents of different types can be used in the same cell. Furthermore, variation
      in base preferences of the individual structural repeats that make up the TAL
      effector DNA recognition domain makes targeting stringency tunable. Realized
      applications range from genome editing to epigenome modification to targeted gene
      regulation to chromatin labeling and capture. The principles that govern TAL
      effector DNA recognition make TAL effectors well suited for applications relevant
      to plant physiology and metabolism. TAL effector targeting has merits that are
      distinct from those of the RNA-based DNA targeting CRISPR/Cas9 system. 

PMID- 24907531
TI  - The activity of a novel mithramycin analog is related to its binding to DNA,
      cellular accumulation, and inhibition of Sp1-driven gene transcription.
AB  - DIG-MSK (demycarosyl-3D-beta-D-digitoxosyl-mithramycin SK) is a recently isolated
      compound of the mithramycin family of antitumor antibiotics, which includes
      mithramycin A (MTA) and mithramycin SK (MSK). Here, we present evidence that the
      binding of DIG-MSK to DNA shares the general features of other mithramycins such
      as the preference for C/G-rich tracts, but there are some differences in the
      strength of binding and the DNA sequence preferentially recognized by DIG-MSK. We
      aimed at gaining further insights into the DIG-MSK mechanism of action by direct
      comparison with the effects of the parental MTA. Similar to MTA, MSK and DIG-MSK
      accumulated rapidly in A2780, IGROV1 and OVCAR3 human ovarian cancer cell lines,
      and DIG-MSK was a potent inhibitor of both basal and induced expression of an Sp1
      driven luciferase vector. This inhibitory activity was confirmed for the
      endogenous Sp1 gene and a set of Sp-responsive genes, and compared to that of MTA
      and MSK. Furthermore, DIG-MSK was stronger than MTA as inhibitor of Sp3-driven
      transcription and endogenous Sp3 gene expression. Differences in the effects of
      MTA, MSK and DIG-MSK on gene expression may have a large influence on their
      biological activities.

PMID- 24907532
TI  - Biochemical mechanisms of bornyl caffeate induced cytotoxicity in rat
      pheochromocytoma PC12 cells.
AB  - The chemopreventive and antineoplastic activities of caffeic acid derivatives are
      highly dependent on the chemical structures and cancer cell types. The objective
      of the present study was to investigate the cytotoxicity of bornyl caffeate and
      the underlying molecular mechanisms in rat pheochromocytoma PC12 cells. Our
      initial studies demonstrated that bornyl caffeate exhibited potent cytotoxicity
      in PC12 cells in a concentration- and time-dependent manner. By examining the
      cell morphology on a fluorescence microscope and detecting the cell surface
      phosphoserine with Annexin V-FITC, we proposed that bornyl caffeate could induce
      apoptosis in PC12 cells. We tested this hypothesis by investigating the effects
      of bornyl caffeate on several apoptosis-related biomarkers. These experiments
      showed that bornyl caffeate induced the up-regulation of Bax and down-regulation
      of Bcl-xl, the disruption of mitochondrial membrane potential, the activation of
      caspase 3 and the cleavage of PARP. Mechanistic studies further revealed that
      bornyl caffeate caused the depletion of glutathione (GSH), generation of
      superoxide ion and progressive activation of p38 mitogen-activate protein kinase
      (MAPK) and c-Jun N-terminal kinase (JNK) in a concentration-dependent manner. In
      particular, GSH depletion appeared to be the most important mechanism underlying
      the cytotoxicity of bornyl caffeate. The preservation of the intracellular GSH
      contents with N-acetyl-L-cysteine (NAC), GSH and vitamin C abolished the effect
      of bornyl caffeate on the activation of p38 MAPK and JNK, preserved the integrity
      of mitochondrial membrane and ultimately rescued the cells from drug-induced cell
      death. These results suggest that bornyl caffeate induces apoptosis in PC12 cells
      via stimulating the depletion of GSH, the generation of reactive oxygen species
      (ROS) and the dissipation of mitochondrial transmembrane potential.

PMID- 24907533
TI  - Morphological and behavioral evidence for impaired prefrontal cortical function
      in female CB1 receptor deficient mice.
AB  - The medial prefrontal cortex (mPFC) is known to regulate higher order processes
      like cognitive flexibility. Accumulating behavioral evidence suggests that
      endocannabinoid (eCB) signaling regulates neuronal architecture within the PFC,
      as well as certain forms of cognitive flexibility; however, all of these studies
      have been performed in male rodents and it is currently unknown whether the eCB
      system performs a similar role in females. To this extent, dendritic morphology
      of layer II/III neurons in the infra- and prelimbic regions of the mPFC was
      analyzed and cognitive ability and flexibility in a fixed-platform Morris water
      maze task was assessed in adult female CB1 receptor knockout (CB1KO) mice.
      Similar to data generated in male mice, female mice exhibited no difference in
      acquisition relative to wildtype (WT); however, during reversal learning, CB1KO
      females spent more time in the original training quadrant and took significantly
      longer to learn the location of the new platform relative to WT. Within the mPFC,
      female mice had reduced length and complexity of layer II/III neurons within the
      prelimbic, but not infralimbic region of the PFC. Taken together, these findings
      indicate that the role of eCB signaling in cognitive flexibility is independent
      of sex and disrupted CB1 receptor signaling results in compromised structure and
      function of the PFC, at least within the prelimbic division. 

PMID- 24907534
TI  - Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of
      coproporphyrinogen oxidase.
AB  - BACKGROUND: Topical 5-aminolevulinic acid-mediated photodynamic therapy (topical
      ALA-PDT) is effective for treating oral precancerous lesions. The aim of this in
      vivo and in vitro study was to examine whether the efficacy of topical ALA-PDT
      could be further improved by calcipotriol (CAL). METHODS: Precancerous lesions in
      the buccal pouch of hamsters were induced by dimethylbenz(a)anthracene (DMBA).
      Lesions were treated with multiple topical ALA-PDT with or without CAL
      pretreatment. ALA-induced protoporphyrine IX (PpIX) was monitored by in situ
      fluorescence measurement. The effect of CAL on heme-related enzymes (CPOX, PPOX,
      and FECH) were examined in an in vitro model using human squamous cell carcinoma
      (SCC) cells (SCC4, SAS) using Western blots. RESULTS: Fluorescence spectroscopy
      revealed that PpIX reached its peak level in precancerous epithelial cells of
      buccal pouch at 2.5 or 3.5h without or with CAL pretreatment, respectively. Both
      treatment regimens showed similar response rates, but the complete response was
      achieved after 5 times of ALA-PDT and 3 times of CAL-ALA-PDT (p<0.001).
      Pretreatment of SCC cells with 10(-8) or 10(-7)M CAL could result in a
      significant cell death (p<0.05) and an elevation of CPOX protein level.
      CONCLUSION: Topical CAL can improve the efficacy of ALA-PDT in treating
      precancerous lesions, likely through the increase in CPOX level and in PpIX
      production.

PMID- 24907535
TI  - An analysis of post-traumatic stress symptoms in United States Air Force drone
      operators.
AB  - Remotely piloted aircraft (RPA), commonly referred to as "drones," have emerged
      over the past decade as an innovative warfighting tool. Given there is a paucity
      of empirical research assessing drone operators, the purpose of this study was to
      assess for the prevalence of PTSD symptoms among this cohort. Of the 1084 United
      States Air Force (USAF) drone operators that participated, a total of 4.3%
      endorsed a pattern of symptoms of moderate to extreme level of severity meeting
      criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders
      4th edition. The incidence of PTSD among USAF drone operators in this study was
      lower than rates of PTSD (10-18%) among military personnel returning from
      deployment but higher than incidence rates (less than 1%) of USAF drone operators
      reported in electronic medical records. Although low PTSD rates may be promising,
      limitations to this study are discussed. 

PMID- 24907536
TI  - Intermittent explosive disorder: associations with PTSD and other Axis I
      disorders in a US military veteran sample.
AB  - This study examined the prevalence of intermittent explosive disorder (IED) and
      its associations with trauma exposure, posttraumatic stress disorder (PTSD), and
      other psychiatric diagnoses in a sample of trauma-exposed veterans (n=232) with a
      high prevalence of PTSD. Structural associations between IED and latent
      dimensions of internalizing and externalizing psychopathology were also modeled
      to examine the location of IED within this influential structure. Twenty-four
      percent of the sample met criteria for a lifetime IED diagnosis and those with
      the diagnosis were more likely to meet criteria for lifetime PTSD than those
      without (30.3% vs. 14.3% respectively). Furthermore, regression analyses revealed
      lifetime PTSD severity to be a significant predictor of IED severity after
      controlling for combat, trauma exposure, and age. Finally, confirmatory factor
      analysis revealed significant cross-loadings of IED on both the externalizing and
      distress dimensions of psychopathology, suggesting that the association between
      IED and other psychiatric disorders may reflect underlying tendencies toward
      impulsivity and aggression and generalized distress and negative emotionality,
      respectively. 

PMID- 24907537
TI  - Single-cell trapping and selective treatment via co-flow within a microfluidic
      platform.
AB  - Lab on a chip (LOC) systems provide interesting and low-cost solutions for key
      studies and applications in the biomedical field. Along with microfluidics, these
      microdevices make single-cell manipulation possible with high spatial and
      temporal resolution. In this work we have designed, fabricated and characterized
      a versatile and inexpensive microfluidic platform for on-chip selective single
      cell trapping and treatment using laminar co-flow. The combination of co-existing
      laminar flow manipulation and hydrodynamic single-cell trapping for selective
      treatment offers a cost-effective solution for studying the effect of novel drugs
      on single-cells. The operation of the whole system is experimentally simple,
      highly adaptable and requires no specific equipment. As a proof of concept, a
      cytotoxicity study of ethanol in isolated hepatocytes is presented. The developed
      microfluidic platform controlled by means of co-flow is an attractive and
      multipurpose solution for the study of new substances of high interest in cell
      biology research. In addition, this platform will pave the way for the study of
      cell behavior under dynamic and controllable fluidic conditions providing
      information at the individual cell level. Thus, this analysis device could also
      hold a great potential to easily use the trapped cells as sensing elements
      expanding its functionalities as a cell-based biosensor with single-cell
      resolution. 

PMID- 24907538
TI  - Immunochromatographic strip for rapid detection of Cronobacter in powdered infant
      formula in combination with silica-coated magnetic nanoparticles separation and
      16S rRNA probe.
AB  - Here we developed a sensitive, specific, and rapid immunochromatographic strip
      test for the detection of Cronobacter. Silica-coated magnetic nanoparticles were
      used to separate nucleic acid from Cronobacter lysate and eliminate the
      interference of food matrices successfully. A couple of 5'-end labeled probes,
      which was complementary to the 16S ribosomal DNA of Cronobacter, was used to
      hybridize with the nucleic acid. The hybrid product, labeled with digoxigenin on
      one side and biotin on the other side, was directly submitted to the
      immunochromatographic strip test and the anti-digoxigenin monoclonal antibody was
      immobilized on nitrocellulose membrane in the test line. The visualization was
      achieved by gold nanoparticles conjugated to streptavidin, and double red bands
      appearing in both test and control line indicated a positive result of the
      presence of Cronobacter in testing sample. The detection limit was 10(7) cfu mL(
      1) in pure culture. After silica-coated magnetic nanoparticles treatment, the
      detection limit was 10(5) and 10(6) cfu mL(-1) in pure culture and powdered
      infant formula, respectively, and maintained stable even under the interference
      of 10(8) cfu mL(-1)Salmonella typhimurium. Furthermore, 100 positive powdered
      infant formula samples spiked 10(8) cfu mL(-1)Cronobacter and 20 negative samples
      with none bacteria were tested by the strip, and the sensitivity and specificity
      of the test were both as high as 100%. This approach showed promise for microbial
      detection concerning food safety or clinical diagnosis.

PMID- 24907539
TI  - Signal enhancement strategy for a micro-arrayed polydiacetylene (PDA)
      immunosensor using enzyme-catalyzed precipitation.
AB  - This paper describes a signal enhancement strategy to improve the sensitivity of
      an antibody-based immunosensor that uses polydiacetylene (PDA) liposomes to
      detect a target protein (human immunoglobulin E [hIgE]). To achieve
      ultrasensitive detection, multiple stimuli applied to PDA immunosensor chips
      offer a signal enhancement method that combines the primary immune reaction
      between antigen and antibody with the sandwich method of polyclonal antibody
      (pAb)-conjugated horseradish peroxidase (HRP). In the second step, fluorescence
      is enhanced by the mechanical pressure from the precipitate formed by enzyme
      catalysis. In order to detect hIgE, the surface of immobilized PDA liposomes was
      conjugated with monoclonal antibodies against hIgE, and fluorescence signals were
      detected after the antigen-antibody reaction. In this step, hIgE concentrations
      as low as 10 ng/mL were detected. Fluorescence signals slightly increased when
      anti-hIgE pAb-HRP was used as an amplifying agent after primary immunoresponse.
      After secondary immunoresponse, HRP-catalyzed oxidation of 3,3'-diaminobenzidine
      produced an insoluble precipitate that strongly stimulated PDA liposomes by their
      weight and pressure, thereby dramatically increasing the fluorescence signal.
      Thus, PDA liposome immunosensor could detect hIgE concentrations as low as 0.01
      ng/mL, representing a 1000-fold increase in sensitivity over the signal generated
      by the primary immunoresponse. This study indicates that increasing the external
      mechanical force applied to PDA liposomes by enzyme-catalyzed precipitate
      formation enhanced the sensitivity of the PDA liposome immunosensor chip. This
      strategy can be applied to the detection of other biomolecules in experimental or
      clinical settings where ultrasensitive and highly specific biosensing is
      required.

PMID- 24907540
TI  - A versatile biosensing system for DNA-related enzyme activity assay via the
      synthesis of silver nanoclusters using enzymatically-generated DNA as template.
AB  - In the present day, oligonucleotide-encapsulated silver clusters (DNA-AgNCs) have
      been widely applied into bio-analysis as a signal producer. Herein, we developed
      a novel method to synthesize DNA-AgNCs encapsulated by long-chain cytosine (C)
      rich DNA. Such DNA was polymerized in a template-free way by terminal
      deoxynucleotidyl transferase (TdT). We demonstrated that TdT-polymerized long
      chain C-rich DNA can serve as an excellent template for AgNCs synthesis. Based on
      this novel synthesis strategy, we developed a label-free and turn-on fluorescence
      assay to detect TdT activity with ultralow limit of detection (LOD) of 0.0318 U
      and ultrahigh signal to background (S/B) of 46.7. Furthermore, our proposed
      method was extended to a versatile biosensing strategy for turn-on nucleases
      activity assay based on the enzyme-activated TdT polymerization. Two nucleases,
      EcoRI and ExoIII as model of endonuclease and exonuclease, respectively, have
      been detected with high selectivity and competitive low LOD of 0.0629 U and
      0.00867 U, respectively. Our work demonstrates the feasibility of TdT
      polymerization-based DNA-AgNCs synthesis strategy as a versatile and potent
      biosensing platform to detect the activity of DNA-related enzymes.

PMID- 24907541
TI  - Case report: Successful treatment of recurrent chordoma and bilateral pulmonary
      metastases following an 11-year disease-free period.
AB  - INTRODUCTION: Chordomas are rare but aggressive tumors due to local recurrence
      and distant metastases. They originate commonly in the sphenooccipital and
      sacrococcygeal regions, and metastasize to the lungs, bone, skin, liver, and
      lymph nodes. They occur more frequently in men and people over the age of 40.
      PRESENTATION OF CASE: A 28 year-old female presented with sacrococcygeal chordoma
      for which she received wide local excision and adjuvant radiation therapy. She
      enjoyed an unusual disease-free survival for 11 years until a routine
      surveillance scan of the pelvis identified local recurrence. Further work up
      revealed bilateral pulmonary metastases. She underwent local excision of the
      recurrent tumor and video-assisted thoracoscopic (VATS) wedge resection of
      pulmonary metastases. She also received adjuvant radiation therapy to the
      recurrent resection bed. Two years later, she remains free of disease and
      symptoms. DISCUSSION: Chordomas are commonly insensitive to chemotherapy and
      radiation, making surgery the most successful therapeutic modality. However,
      there are few guidelines on the surveillance and treatment of recurrent chordoma.
      We report success with aggressive surgical resection of recurrence and metastasis
      as well as adjuvant radiation therapy. CONCLUSION: The prolonged survival of our
      patient underscores the importance of (1) aggressive surgical resection of
      chordoma, whether primary, recurrent, or metastatic, with adjuvant radiation
      therapy, (2) minimization of surgical seeding of tumor, and (3) diligent cancer
      surveillance.

PMID- 24907542
TI  - Measurement of blood pressure in a thalidomide-impaired patient who required
      ovarian cystectomy: A case report.
AB  - INTRODUCTION: Thalidomide was available for use over-the-counter between 1958 and
      1962, and more than 300 thalidomide-impaired people have been confirmed in Japan.
      Currently, thalidomide-impaired people are nearing the age of 50 years and
      sometimes require medical treatment or surgery. However, a sphygmomanometer
      cannot be used to measure the blood pressure in some thalidomide-impaired people
      because of upper-limb shortening or hypoplastic defects. We encountered a patient
      with thalidomide-related upper limb defects who required abdominal ovarian
      cystectomy. PRESENTATION OF CASE: The patient was a 49-year-old woman (146.5cm,
      35.9kg) with thalidomide-related upper-limb defects, but no dysplasia of the
      lower limbs, who underwent abdominal ovarian cystectomy. During the surgery, the
      patient's arterial blood pressure was monitored in her lower limbs by both non
      invasive and invasive methods, and almost the same variations of the blood
      pressure between the invasive and non-invasive measurements were observed.
      DISCUSSION: Usually, blood pressure measurements are performed in a non-invasive
      manner in the upper limbs, however, such measurement could not be performed in
      the present case. There are few reports of measurement of the blood pressure or
      surgery under anaesthesia in thalidomide-impaired patients, and we report here
      that it was useful to measure the blood pressure in the lower limbs in the
      current patient. Invasive arterial pressure measurements showed almost the same
      changes as the non-invasive pressure measurements, although the systolic blood
      pressure was 10-20mmHg lower than the noninvasively measured systolic blood
      pressure. CONCLUSION: Non-invasive blood pressure measurements in the lower limbs
      might be useful in thalidomide-impaired patients requiring blood pressure
      monitoring, but further studies are required to validate this method.

PMID- 24907543
TI  - Gastric diverticulum and halitosis-A case for surgery?
AB  - INTRODUCTION: Gastric diverticulum is a rare and frequently asymptomatic
      condition. Symptoms include vague pain, fullness, dyspepsia, vomiting, hemorrhage
      and perforation. Occasionally, the patient can present with belching and oral
      fetor. PRESENTATION OF CASE: We report a 58-year-old woman with a gastric
      diverticulum who was suffering from a socially disabling oral fetor. After a
      thorough evaluation, a laparoscopic resection of the diverticulum was offered and
      completed successfully. At follow-up, the oral fetor had disappeared. The patient
      had no complaints and regarded herself as cured. DISCUSSION: Although indications
      for the treatment of asymptomatic patients remain to be defined, pharmacological
      therapies including protein pump inhibitors and histamine receptor blockers have
      been employed, with limited effects in patients with miscellaneous symptoms.
      Surgery is required when serious complications such as hemorrhage or perforation
      of the diverticulum occur. CONCLUSION: Surgery is required when serious
      complications such as hemorrhage or perforation of the diverticulum occur.
      Therapy resistent social disabling oral fetor may add to the indications for
      surgery.

PMID- 24907544
TI  - Simultaneous determination of eight flavonoids in propolis using chemometrics
      assisted high performance liquid chromatography-diode array detection.
AB  - A fast analytical strategy of second-order calibration method based on the
      alternating trilinear decomposition algorithm (ATLD)-assisted high performance
      liquid chromatography coupled with a diode array detector (HPLC-DAD) was
      established for the simultaneous determination of eight flavonoids (rutin,
      quercetin, luteolin, kaempferol, isorhamnetin, apigenin, galangin and chrysin) in
      propolis capsules samples. The chromatographic separation was implemented on a
      WondasilTM C18 column (250mm*4.6mm, 5MUm) within 13min with a binary mobile phase
      composed of water with 1% formic acid and methanol at a flow rate of 1.0mLmin(-1)
      after flavonoids were only extracted with methanol by ultrasound extraction for
      15min. The baseline problem was overcome by considering background drift as
      additional compositions or factors as well as the target analytes, and ATLD was
      employed to handle the overlapping peaks from analytes of interest or from
      analytes and co-eluting matrix compounds. The linearity was good with the
      correlation coefficients no less than 0.9947; the limit of detections (LODs)
      within the range of 3.39-33.05ngmL(-1) were low enough; the accuracy was
      confirmed by the recoveries ranged from 91.9% to 110.2% and the root-mean-square
      error of predictions (RMSEPs) less than 1.1MUg/mL. The results indicated that the
      chromatographic method with the aid of ATLD is efficient, sensitive and cost
      effective and can realize the resolution and accurate quantification of
      flavonoids even in the presence of interferences, thus providing an alternative
      method for accurate quantification of analytes especially when the complete
      separation is not easily accomplished. The method was successfully applied to
      propolis capsules samples and the satisfactory results were obtained. 

PMID- 24907545
TI  - Validation of a UHPLC-MS/MS method for quantification of zearalenone, alpha
      zearalenol, beta-zearalenol, alpha-zearalanol, beta-zearalanol and zearalanone in
      human urine.
AB  - Humans can be exposed to mycotoxins through the diet. Evaluation of exposure
      levels to mycotoxins can be performed by direct determination in urine. The
      present work proposes a sensitive ultrahigh-performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS) method for the determination of
      zearalenone (ZON) and its five metabolites (alpha-zearalenol [alpha-ZOL], beta
      zearalenol [beta-ZOL], alpha-zearalanol [zeranol, alpha-ZAL], beta-zearalanol
      [teranol, beta-ZAL] and zearalanone [ZAN]) in human urine samples. The method
      involves the enzymatic hydrolysis of the samples, extraction of the analytes
      using liquid-liquid extraction (LLE) with ethyl acetate/formic acid (99:1 v/v)
      and a cleanup step using hexane, prior to their quantification by UHPLC-MS/MS,
      using an electrospray ionization (ESI) interface in the negative mode.
      Zearalenone-d6 (ZON-d6) was used as surrogate. The limits of detection and the
      limits of quantification ranged from 0.03 to 0.3ngmL(-1) and from 0.1 to 1.0ngmL(
      1), respectively. The method was validated using matrix-matched calibration and a
      spike recovery assay. Recovery rates for spiked samples ranged from 96% to 104%,
      with relative standard deviations lower than 8.5%. This method was satisfactorily
      applied to 42 urine samples from Tunisian women for the determination of
      zearalenone and its five metabolites. 

PMID- 24907546
TI  - Simultaneous determination of paeoniflorin, albiflorin, ferulic acid,
      tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs
      plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral
      Administration of Shaofu Zhuyu Decoction.
AB  - In this present study, a sensitive and rapid UPLC-MS/MS method was developed for
      simultaneous quantification of paeoniflorin, albiflorin, ferulic acid,
      tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog
      plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol
      and clarithromycin were used as internal standards. Plasma samples were processed
      by protein precipitation with methanol. The separation was performed on an
      Acquity BEH C18 column (100mm*2.1mm, 1.7MUm) at a flow-rate of 0.4mL/min, using
      0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as
      per Food and Drug Administration guidelines and the results met the acceptance
      criteria. After validation, this method was successfully applied to a
      pharmacokinetic study. The results showed that the apparent plasma clearance of
      paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly
      higher than others. Double peak was observed in plasma concentration curves of
      tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma,
      and senkyunolide I was detected in plasma from the first blood sampling time
      (15min) and rapidly reached Tmax. The compound of typhaneoside has a low
      bioavailability according to the results. 

PMID- 24907547
TI  - Simultaneous determination of gabapentin, pregabalin, vigabatrin, and topiramate
      in plasma by HPLC with fluorescence detection.
AB  - Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) has been
      recognized as a useful tool in management of epilepsy. We developed a simple
      analytical method for simultaneous determination of four second generation AEDs,
      including gabapentin (GBP), pregabalin (PGB), vigabatrin (VGB), and topiramate
      (TOP). Analytes were extracted from human plasma using universal solid phase
      extraction, derivatized with 4-chloro-7-nitrobenzofurazan (NBD-Cl) and analyzed
      by HPLC with fluorescence detection. Using mass spectrometry we confirmed that
      NBD-Cl reacts with sulfamate group of TOP similarly as with amine group of the
      other three analytes. The method is linear (r(2)>0.998) across investigated
      analytical ranges (0.375-30.0MUg/mL for GBP, PGB, and VGB; 0.50-20.0MUg/mL for
      TOP). Intraday and interday precision do not exceed 9.40%. The accuracy is from
      95.6% to 106%. The recovery is higher than 80.6%, and the lower limit of
      quantification is at least 0.5MUg/mL. The method is selective and robust. For TOP
      determination the method was compared to a previously published method and the
      results obtained by the two methods were in good agreement. The developed method
      is suitable for routine TDM. 

PMID- 24907548
TI  - Separation of human immunoglobulin G subclasses on a protein A monolith column.
AB  - Monolithic columns have attracted significant attention for the purification of
      large biomolecules. In the present study, a step gradient elution method was
      evaluated for the separation of human immunoglobulin G (hIgG) into its subclasses
      on CIM (convective interaction media) r-protein A (recombinant protein A)
      monolithic column. hIgG was loaded onto the column and bound protein was eluted
      with a pH gradient. The subclass content of the eluted fractions was analyzed by
      enzyme-linked immunosorbent assay (ELISA). Results showed that separation of IgG3
      from the other three subclasses can be successfully achieved with high
      selectivity (100%) and throughput on monolithic media. It was also revealed that
      enriched fractions of IgG1 and IgG2 could be obtained from purified hIgG in a
      28min long chromatographic run. Three fractions with high IgG1 content (89.1%,
      94.3% and 88.8%) were recovered. Furthermore, IgG2 was enriched to 64%
      successfully. A rapid step gradient elution scheme without any additives in
      buffers was proven to obtain enriched preparations of the two important
      subclasses with high throughput. The separation time can be reduced even more by
      increasing the flow rate without any loss in selectivity, which will be
      beneficial in industrial scale applications. 

PMID- 24907550
TI  - Technical video: modified laparoscopic colposuspension.
AB  - BACKGROUND: Laparoscopic colposuspension has been shown in some studies to have
      equivocal results as open colposuspension, and in addition to treating stress
      incontinence can also reduce anterior vaginal wall compartment prolapse, as
      described by Burch in 1961 [1]. STUDY OBJECTIVE: To demonstrate a novel modified
      technique for laparoscopic colposuspension. DESIGN: Narrated step-by-step video
      demonstration of the modified laparoscopic colposuspension technique. SETTING:
      Department of Obstetrics and Gynecology, Royal Surrey County Hospital.
      INTERVENTION: Initially, 180 mL methylene blue with saline solution is instilled
      into the bladder for clear identification. Incision and dissection bilaterally,
      directly onto the ileopectineal ligament (Cooper's ligament) are performed. By
      using the Kent dissecting knotter, dissection down the space of Retzius to the
      paravaginal tissues is easily performed. Two 0 Ethibond sutures (Ethicon, Inc.,
      Somerville, NJ) are then placed on each side, between the Cooper's ligament and
      the paravaginal tissues. These are tied via an extracorporeal knot using the
      other end of the Kent dissecting knotter. The peritoneal defects are then closed
      sequentially using 2/0 polyglactin 910 sutures (Vicryl; Ethicon) in a figure-of
      eight intracorporeal surgical slip knot technique. MAIN RESULTS: The patient had
      second-degree anterior wall prolapse with proved stress incontinence and descent
      of the bladder neck observed on video urodynamics. At 8 months after surgery she
      has no symptomatic or measurable prolapse and no stress incontinence. CONCLUSION:
      This modified laparoscopic colposuspension procedure can be used in most cases
      because it is a transperitoneal technique. It requires substantially less
      dissection than the traditional techniques do, which results in a markedly
      reduced operative time.

PMID- 24907549
TI  - Trends in reported resident surgical experience in hysterectomy.
AB  - STUDY OBJECTIVE: To compare differences in trends in reported surgical experience
      of residents in obstetrics and gynecology in the United States insofar as
      abdominal, vaginal, and laparoscopic hysterectomy. DESIGN: Retrospective analysis
      of the national case log reports from the Accreditation Council for Graduate
      Medical Education (ACGME) for obstetrics and gynecology cases logged as "surgeon"
      from 2002 to 2012 (Canadian Task Force classification III). SETTING: AGCME
      accredited residency programs in obstetrics and gynecology. PARTICIPANTS: Eleven
      thousand five hundred and eight graduating residents in obstetrics and gynecology
      (n = 11 508). MEASUREMENTS AND MAIN RESULTS: Since 2008, when the ACGME began
      reporting the 4-year cumulative hysterectomy case load statistics for graduating
      residents in obstetrics and gynecology, there has been no significant change in
      the mean (SD) number of hysterectomies performed by residents from 118.1 (38.0)
      cases in 2008-2009 to 116.1 (31.0) cases in 2011-2012 (p = .16; 95% confidence
      interval [CI], -0.78 to 4.78). During the past decade, however, the total number
      of reported abdominal hysterectomies consistently decreased from 89.1 (34.2)
      cases in 2002-2003 to 59.1 (21.0) cases in 2011-2012 (28% decrease; p <.001; 95%
      CI, 27.7-32.3). The number of vaginal hysterectomies also trended down from 34.9
      (19.2) cases to 19.4 (9.0) cases (40% decrease; p <.001; 95% CI, 14.3-16.7). The
      ACGME did not report the number of laparoscopic hysterectomies performed by
      residents until 2008-2009, when residents reported performing 23.4 (17.0) cases.
      From 2008 to 2012, this number increased to 38.5 (20.0) cases (72% increase; p
      <.001; 95% CI, 13.6-16.6). The proportion of reported laparoscopic hysterectomies
      performed with robotic assistance was not separately reported. CONCLUSIONS:
      Although the overall number of hysterectomies reported by residents has remained
      stable since 2008, the predominant modes of hysterectomy during the past decade
      have changed substantially, with laparoscopic hysterectomy comprising an
      increasingly large proportion of resident experience. As laparoscopic
      hysterectomy has become more common, reported cases of abdominal and vaginal
      hysterectomies have decreased. Additional statistics on the percentage of
      laparoscopic hysterectomies performed using robotic assistance would be valuable
      to additionally analyze the effect of this new technology on resident training.

PMID- 24907551
TI  - Pre and post-conceptional abdominal cerclage by laparoscopy or laparotomy.
AB  - The objective of this study was to evaluate the efficacy of abdominal cerclage
      via laparoscopy vs laparotomy and before vs after conception. We evaluated 16
      studies of abdominal cerclage involving a total of 678 cases published between
      1990 and 2013. We estimated the effect of laparotomy over laparoscopy and the
      effect of preconceptional over postconceptional cerclage using a generalized
      linear model by treating the success rates (third-trimester delivery and live
      birth) as dependent variables and laparotomy and preconceptional as independent
      factors. The results demonstrated that there was no difference in the rates of
      third-trimester delivery and live birth rates between preconceptional abdominal
      cerclage via laparoscopy (71.4%-83.3% and 90%-100%, respectively) or laparotomy
      (97.3%-100% and 100%, respectively). For postconceptional cerclage, the rates of
      third-trimester delivery and live birth via laparoscopy were 70% and 70% to 100%,
      respectively, and via laparotomy were 77.4% to 99.5% and 85.2% to 100%,
      respectively. There was no difference in the live birth rates when abdominal
      cerclage was performed before or during pregnancy. We concluded that the rates of
      third-trimester delivery and live birth after abdominal cerclage via laparoscopy
      are high and comparable to those via laparotomy. The efficacy of the procedure
      performed either before or during pregnancy is similar. Abdominal cerclage
      performed before conception is more practical than after conception. With the
      inherent advantages of laparoscopy over laparotomy, abdominal cerclage performed
      via laparoscopy is preferable, in particular when performed in non-pregnant
      women. 

PMID- 24907552
TI  - Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with
      neutralizing and non-neutralizing single-chain antibodies.
AB  - Ricin is a select agent toxin and a member of the RNA N-glycosidase family of
      medically important plant and bacterial ribosome-inactivating proteins. In this
      study, we determined X-ray crystal structures of the enzymatic subunit of ricin
      (RTA) in complex with the antigen binding domains (VHH) of five unique single
      chain monoclonal antibodies that differ in their respective toxin-neutralizing
      activities. None of the VHHs made direct contact with residues involved in RTA's
      RNA N-glycosidase activity or induced notable allosteric changes in the toxin's
      subunit. Rather, the five VHHs had overlapping structural epitopes on the surface
      of the toxin and differed in the degree to which they made contact with prominent
      structural elements in two folding domains of the RTA. In general, RTA
      interactions were influenced most by the VHH CDR3 (CDR, complementarity
      determining region) elements, with the most potent neutralizing antibody having
      the shortest and most conformationally constrained CDR3. These structures provide
      unique insights into the mechanisms underlying toxin neutralization and provide
      critically important information required for the rational design of ricin toxin
      subunit vaccines. 

PMID- 24907554
TI  - Ligand heterogeneity of the cysteine protease binding protein family in the
      parasitic protist Entamoeba histolytica.
AB  - Lysosomal soluble proteins are targeted to endosomes and lysosomes by specific
      receptors resident in the endoplasmic reticulum and/or the Golgi apparatus. The
      enteric protozoan parasite Entamoeba histolytica has a novel class of lysosomal
      targeting receptors, named the cysteine protease binding protein family (CPBF).
      Among 11 CPBFs (CPBF1-11), ligands for three members, CPBF1, CPBF6 and CPBF8,
      were previously shown to be cysteine proteases, alpha- and gamma- amylases, and
      beta-hexosaminidase and lysozymes, respectively. To further understand the
      heterogeneity of the ligands of CPBFs, we attempted to isolate and identify the
      ligands for other members of CPBFs, namely CPBF2, 3, 4, 5, 7, 9, 10 and 11, by
      immunoprecipitation and mass spectrometric analysis. We found that CPBF2 and
      CPBF10 bound to alpha-amylases while CPBF7 bound to beta-hexosaminidases. It is
      intriguing that cysteine protease are exclusively recognised by CPBF1, whereas
      three alpha-amylases and beta-hexosaminidases are redundantly recognised by three
      and two CPBFs, respectively. It was shown by bioinformatics analysis and
      phylogenetic reconstruction that each CPBF contains six prepeptidase carboxyl
      terminal domains, and the domain configuration is evolutionarily conserved among
      CPBFs. Taken together, CPBFs with unique and conserved domain organisation have a
      remarkable ligand heterogeneity toward cysteine protease and carbohydrate
      degradation enzymes. Further structural studies are needed to elucidate the
      structural basis of the ligand specificity. 

PMID- 24907553
TI  - Vaccines to combat river blindness: expression, selection and formulation of
      vaccines against infection with Onchocerca volvulus in a mouse model.
AB  - Human onchocerciasis is a neglected tropical disease caused by Onchocerca
      volvulus and an important cause of blindness and chronic disability in the
      developing world. Although mass drug administration of ivermectin has had a
      profound effect on control of the disease, additional tools are critically needed
      including the need for a vaccine against onchocerciasis. The objectives of the
      present study were to: (i) select antigens with known vaccine pedigrees as
      components of a vaccine; (ii) produce the selected vaccine antigens under
      controlled conditions, using two expression systems and in one laboratory and
      (iii) evaluate their vaccine efficacy using a single immunisation protocol in
      mice. In addition, we tested the hypothesis that joining protective antigens as a
      fusion protein or in combination, into a multivalent vaccine, would improve the
      ability of the vaccine to induce protective immunity. Out of eight vaccine
      candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to
      reproducibly induce protective immunity when administered individually, as fusion
      proteins or in combination. Although there was no increase in the level of
      protective immunity induced by combining the antigens into one vaccine, these
      antigens remain strong candidates for inclusion in a vaccine to control
      onchocerciasis in humans. 

PMID- 24907555
TI  - Analysis of putative inhibitors of anthelmintic resistance mechanisms in cattle
      gastrointestinal nematodes.
AB  - Effects of the cytochrome P450 inhibitor piperonyl butoxide and the P
      glycoprotein inhibitor verapamil on the efficacy of ivermectin and thiabendazole
      were studied in vitro in susceptible and resistant isolates of the cattle
      parasitic nematodes Cooperia oncophora and Ostertagia ostertagi. The effects of
      combined use of drug and piperonyl butoxide/verapamil, respectively, were
      investigated in the Egg Hatch Assay, the Larval Development Assay and the Larval
      Migration Inhibition Assay. The effects of piperonyl butoxide and verapamil as
      inhibitors of thiabendazole and ivermectin responses were particularly marked for
      larval development, where both inhibitors were able to completely eliminate all
      differences between susceptible and resistant isolates. Even the lowest
      concentrations of anthelmintics used in combination with inhibitors caused
      complete inhibition of development. Differences and/or similarities among
      responses in different isolates were only obtained in the two other assays: in
      the Egg Hatch Assay piperonyl butoxide caused a shift in concentration-response
      curves obtained with thiabendazole to the left for all isolates tested, changing
      relative differences between isolates. In contrast, an effect of verapamil in the
      Egg Hatch Assay was only apparent for benzimidazole-resistant isolates. In the
      Larval Migration Inhibition Assay only ivermectin was tested and piperonyl
      butoxide shifted the concentration-response curves for all isolates to the left,
      again eliminating differences in EC50 values between susceptible and resistant
      isolates. This was not the case using verapamil as an inhibitor, where curves for
      both susceptible and benzimidazole-resistant isolates shifted to the left in
      Ostertagia isolates. In Cooperia the picture was more complex with ivermectin
      resistant isolates showing a larger shift than the susceptible isolate. Single
      nucleotide polymorphisms in the beta-tubulin isotype 1 gene were investigated.
      Significantly increased frequencies of resistance-associated alleles were
      observed for the codons 167 and 200 in one benzimidazole-resistant isolate but
      not in an isolate selected for benzimidazole resistance at an early stage of
      selection. 

PMID- 24907556
TI  - Renin-angiotensin-aldosterone system related gene polymorphisms and urinary total
      arsenic is related to chronic kidney disease.
AB  - A recent study demonstrated that an increased risk of chronic kidney disease
      (CKD) was associated with high urinary total arsenic levels. However, whether
      genomic instability is related to CKD remains unclear. An association between CKD
      and genetic polymorphisms of regulation enzymes of the renin-angiotensin
      aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE),
      angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone
      synthase (CYP11B2) has not been shown. The aim of the present study was to
      investigate the relationship between arsenic, genetic polymorphisms of RAAS
      enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls
      were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan
      Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of
      urinary arsenic were determined by a high-performance liquid chromatography
      linked hydride generator, and atomic absorption spectrometry. Polymorphisms of
      ACE(I/D), AGT(A[-20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[-344]T) were
      examined by polymerase chain reaction and restriction fragment length
      polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio
      (OR), 1.39 (0.96-2.01), of CKD; while those with the AGT(A[-20]C) CC genotype had
      an inverse OR of CKD (0.20 (0.05-0.81)), and a high-risk genotype was defined as
      A/A+A/C for AGT(A[-20C]) and T/T for CYP11B2(C[-344]T). The trend test showed a
      higher OR for CKD in patients who had either high urinary total arsenic levels or
      carried the high-risk genotype, or both, compared to patients with low urinary
      total arsenic levels, who carried the low-risk genotype, and could also be
      affected by the hypertension or diabetes status. 

PMID- 24907557
TI  - Evidence for a role of claudin 2 as a proximal tubular stress responsive
      paracellular water channel.
AB  - Claudins are the major proteins of the tight junctions and the composition of
      claudin subtypes is decisive for the selective permeability of the paracellular
      route and thus tissue specific function. Their regulation is complex and subject
      to interference by several factors, including oxidative stress. Here we show that
      exposure of cultured human proximal tubule cells (RPTEC/TERT1) to the
      immunosuppressive drug cyclosporine A (CsA) induces an increase in
      transepithelial electrical resistance (TEER), a decrease in dome formation (on
      solid growth supports) and a decrease in water transport (on microporous growth
      supports). In addition, CsA induced a dramatic decrease in the mRNA for the pore
      forming claudins -2 and -10, and the main subunits of the Na(+)/K(+) ATPase.
      Knock down of claudin 2 by shRNA had no discernable effect on TEER or dome
      formation but severely attenuated apical to basolateral water reabsorption when
      cultured on microporous filters. Generation of an osmotic gradient in the
      basolateral compartment rescued water transport in claudin 2 knock down cells.
      Inhibition of Na(+)/K(+) ATPase with ouabain prevented dome formation in both
      cell types. Taken together these results provide strong evidence that dome
      formation is primarily due to transcellular water transport following a solute
      osmotic gradient. However, in RPTEC/TERT1 cells cultured on filters under iso
      osmotic conditions, water transport is primarily paracellular, most likely due to
      local increases in osmolarity in the intercellular space. In conclusion, this
      study provides strong evidence that claudin 2 is involved in paracellular water
      transport and that claudin 2 expression is sensitive to compound induced cellular
      stress. 

PMID- 24907558
TI  - The national-scale cohort study on bisphosphonate-related osteonecrosis of the
      jaw in Taiwan.
AB  - OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potential side effect of
      bisphosphonate therapy. This Taiwanese national-scale cohort study aimed to
      investigate its incidence and risk of development by using a qualified control
      group with different demographic factors (age/gender), dental (tooth
      extraction/periodontal therapy) and medical (jaw radiotherapy) treatments,
      delivery routes (oral/intravenous), and diseases (diabetes/osteoporosis/cancer).
      METHODS: Data (n=958,136) from January 1, 2006 through December 31, 2008 were
      sourced from the Longitudinal Health Insurance Database 2005 of Taiwan. Cases of
      BRONJ were identified by three criteria modified from the definition proposed by
      the American Association of Oral and Maxillofacial Surgeons. The Cox proportional
      hazards regression model and Kaplan-Meier estimates were used to analyse the
      results. RESULTS: The incidence densities of ONJ in the unexposed and
      bisphosphonate-exposed cohorts were estimated as 4.4 and 73.5 per 100,000 person
      years, respectively (relative risk=16.8; 95% CI=6.0-37.5; P<0.001). Multivariate
      analysis revealed strong associations of delivery route, tooth extraction, and
      oral cancer with ONJ (hazard ratios=51.4 for oral bisphosphonates, 153.3 for
      intravenous bisphosphonates, 5.3 for tooth extraction, and 278.1 for oral
      cancer). CONCLUSIONS: These results not only demonstrate the incidence and
      relative risk of bisphosphonate-related ONJ in Taiwan but also indicate that
      tooth extraction and oral cancer may have a major impact on its development.
      CLINICAL SIGNIFICANCE: Physicians should be aware of individual patient risk
      factors before prescribing bisphosphonates. Bisphosphonate treatment is justified
      in the amelioration of life-threatening conditions in patients in whom ONJ would
      only affect quality of life.

PMID- 24907559
TI  - The effect of a bioglass paste on enamel exposed to erosive challenge.
AB  - OBJECTIVES: The current study is evaluating the effect of using a 45S5 bioglass
      paste and topical fluoride application on the cross sectional micro-hardness and
      the chemical surface changes of eroded enamel. METHODS: Enamel discs were
      obtained from the buccal surface of one hundred extracted human non-carious third
      molars. The enamel surfaces were ground flat and each disc was coated with two
      layers of acid resistant nail varnish except for an exposed treatment window
      (3mm*2mm) on the buccal surface of the tooth. All specimens were challenged for
      60 min by orange juice (Tropicana, Chicago, USA) pH 3.85+0.5. The specimens were
      divided into four groups: the 45S5 bioglass paste group, fluoride gel group (5
      min application), fluoride gel group (24h application) while the rest of
      specimens served as control. The cross-sectional micro-hardness of 20 specimens
      from each group was measured. Five specimens from each group had their top eroded
      enamel surfaces examined by SEM-EDS. One-way ANOVA was used to compare the cross
      sectional micro-hardness of the three groups p<0.05. RESULTS: 45S5 bioglass paste
      application significantly improved the sub-surface eroded enamel when compared to
      fluoride and control specimens (p<0.05). CONCLUSION: 45S5 bioglass paste can
      efficiently improve the micro-hardness of the sub-surface eroded enamel surface.
      CLINICAL SIGNIFICANCE: The use of the 45S5 Bioglass paste can be used efficiently
      as a potent remineralizing agent for the sub-surface enamel lesions resulting
      from erosive challenges.

PMID- 24907560
TI  - Can repair increase the longevity of composite resins? Results of a 10-year
      clinical trial.
AB  - OBJECTIVES: The aim of this double-blind clinical trial was to assess the
      longevity of repairs to localized clinical defects in composite resin
      restorations that were initially planned to be treated with a restoration
      replacement. METHODS: Twenty-eight patients aged 18-80 years old with 50
      composite resin restorations (CR) were recruited. The restorations with
      localized, marginal, anatomical deficiencies and/or secondary caries adjacent to
      CR that were "clinically judged" to be suitable for repair or replacement
      according to the USPHS criteria were randomly assigned to Repair (n=25) or
      Replacement (n=25) groups, and the quality of the restorations was scored
      according to the modified USPHS criteria. The restorations were blind and two
      examiners scored them at baseline (Cohen Kappa agreement score 0.74) and at ten
      years (Cohen Kappa agreement score 0.87) restorations. Wilcoxon tests were
      performed for comparisons within the same group (95% CI), and Friedman tests were
      utilized for multiple comparisons between the different years within each group.
      RESULTS: Over the decade, the two groups behaved similarly on the parameters of
      marginal adaptation (MA) (p>0.05), secondary caries (SC) (p>0.05), anatomy (A)
      (p<0.05), and colour (C) (p>0.05). CONCLUSIONS: Given that the MA, SC, A and C
      parameters behaved similarly in both groups, the repair of composite resins
      should be elected when clinically indicated, because it is a minimally invasive
      treatment that can consistently increase the longevity of restorations. CLINICAL
      SIGNIFICANCE: The repair of defective composite resins as an alternative
      treatment to increase their longevity proved to be a safe and effective treatment
      in the long term.

PMID- 24907561
TI  - Dermatomyositis, polymyositis and immune-mediated necrotising myopathies.
AB  - Dermatomyositis, polymyositis and immune-mediated necrotising myopathy are major
      forms of idiopathic inflammatory myopathy. We review here recent developments in
      understanding the pathology and pathogenesis of these diseases, and
      characterisation of autoantibody biomarkers. Dermatomyositis is traditionally
      considered to be due to a complement-mediated microangiopathy but the factors
      responsible for complement activation remain uncertain. Recent studies have
      emphasised the importance of the type I interferon pathway in the pathogenesis of
      the disease and have identified autoantibodies with specificities for different
      clinical subgroups of patients. Polymyositis is characterised by a cytotoxic T
      cell response targeting as yet unidentified muscle antigens presented by MHC
      Class I molecules, and can occur in isolation but is more often part of a multi
      systemic overlap syndrome. The immune-mediated necrotising myopathies are
      heterogeneous and are distinguished from polymyositis by the sparseness of
      inflammatory infiltrates and recognition of an association with specific
      autoantibodies such as anti-SRP and anti-HMGCR in many cases. This article is
      part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular
      Pathogenesis. 

PMID- 24907563
TI  - Aldosterone signaling and soluble adenylyl cyclase-a nexus for the kidney and
      vascular endothelium.
AB  - The steroid hormone aldosterone regulates the reabsorption of water and ions in
      the kidney and plays a central role in blood pressure regulation and homeostasis.
      In recent years, the vascular endothelium has been established as an important
      aldosterone target organ with major implications in renal and cardiovascular
      health and disease. Different lines of evidence suggest that the calcium- and
      bicarbonate-activated soluble adenylyl cyclase (sAC) is a novel mediator of
      aldosterone signaling in both the kidney and vascular endothelium. This review
      summarizes our current understanding of the molecular mechanisms of sAC gene
      expression regulation in the kidney and vascular endothelium and outlines the
      potential clinical implications of sAC in chronic kidney disease and
      cardiovascular disease. This review is part of a special issue entitled: The role
      of soluble adenylyl cyclase in health and disease. This article is part of a
      Special Issue entitled: The role of soluble adenylyl cyclase in health and
      disease. 

PMID- 24907562
TI  - Defective collagen VI alpha6 chain expression in the skeletal muscle of patients
      with collagen VI-related myopathies.
AB  - Collagen VI is a non-fibrillar collagen present in the extracellular matrix (ECM)
      as a complex polymer; the mainly expressed form is composed of alpha1, alpha2 and
      alpha3 chains; mutations in genes encoding these chains cause myopathies known as
      Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and
      myosclerosis myopathy (MM). The collagen VI alpha6 chain is a recently identified
      component of the ECM of the human skeletal muscle. Here we report that the alpha6
      chain was dramatically reduced in skeletal muscle and muscle cell cultures of
      genetically characterized UCMD, BM and MM patients, independently of the clinical
      phenotype, the gene involved and the effect of the mutation on the expression of
      the "classical" alpha1alpha2alpha3 heterotrimer. By contrast, the collagen VI
      alpha6 chain was normally expressed or increased in the muscle of patients
      affected by other forms of muscular dystrophy, the overexpression matching with
      areas of increased fibrosis. In vitro treatment with TGF-beta1, a potent collagen
      inducer, promoted the collagen VI alpha6 chain deposition in the ECM of normal
      muscle cells, whereas, in cultures derived from collagen VI-related myopathy
      patients, the collagen VI alpha6 chain failed to develop a network outside the
      cells and accumulated in the endoplasmic reticulum. The defect of the alpha6
      chain points to a contribution to the pathogenesis of collagen VI-related
      disorders. 

PMID- 24907565
TI  - sAC as a model for understanding the impact of endosymbiosis on cell signaling.
AB  - As signaling pathways evolve, selection for new functions guides the co-option of
      existing material. Major transitions in the history of life, including the
      evolution of eukaryotes and multicellularity, exemplify this process. These
      transitions provided both strong selection and a plenitude of available material
      for the evolution of signaling pathways. Mechanisms that evolved to mediate
      conflict during the evolution of eukaryotes may subsequently have been co-opted
      during the many independent derivations of multicellularity. The soluble adenylyl
      cyclase (sAC) signaling pathway illustrates this hypothesis. Class III adenylyl
      cyclases, which include sAC, are found in bacteria, including the alpha
      proteobacteria. These adenylyl cyclases are the only ones present in eukaryotes
      but appear to be absent in archaeans. This pattern suggests that the
      mitochondrial endosymbiosis brought sAC signaling to eukaryotes as part of an
      intact module. After transfer to the proto-nuclear genome, this module was then
      co-opted into numerous new functions. In the evolution of eukaryotes, sAC
      signaling may have mediated conflicts by maintaining metabolic homeostasis. In
      the evolution of multicellularity, in different lineages sAC may have been co
      opted into parallel tasks originally related to conflict mediation. Elucidating
      the history of the sAC pathway may be relatively straightforward because it is
      ubiquitous and linked to near universal metabolic by-products (CO2/HCO(3)(-)).
      Other signaling pathways (e.g., those involving STAT and VEGF) present a greater
      challenge but may suggest a complementary pattern. The impact of the
      mitochondrial endosymbiosis on cell signaling may thus have been profound. This
      article is part of a Special Issue entitled: The role of soluble adenylyl cyclase
      in health and disease.

PMID- 24907564
TI  - Role of soluble adenylyl cyclase in mitochondria.
AB  - The soluble adenylyl cyclase (sAC) catalyzes the conversion of ATP into cyclic
      AMP (cAMP). Recent studies have shed new light on the role of sAC localized in
      mitochondria and its product cAMP, which drives mitochondrial protein
      phosphorylation and regulation of the oxidative phosphorylation system and other
      metabolic enzymes, presumably through the activation of intra-mitochondrial PKA.
      In this review article, we summarize recent findings on mitochondrial sAC
      activation by bicarbonate (HCO(3)(-)) and calcium (Ca2+) and the effects on
      mitochondrial metabolism. We also discuss putative mechanisms whereby sAC
      mediated mitochondrial protein phosphorylation regulates mitochondrial
      metabolism. This article is part of a Special Issue entitled: The role of soluble
      adenylyl cyclase in health and disease.

PMID- 24907566
TI  - Influence of carrier filling ratio on the performance of moving bed biofilm
      reactor in treating coking wastewater.
AB  - This study aims to evaluate the effect of carrier filling ratio on the
      performance of a moving bed biofilm reactor in degrading chemical oxygen demand,
      phenol, thiocyanate, and ammonia from coking wastewater at 20h of hydraulic
      retention time. The operational experiments under different carrier filling
      ratios ranging from 20% to 60% were investigated. The maximum removal efficiency
      of 89%, 99% and 99% for COD, phenol and thiocyanate, and minimum sensitivity to
      the increasing contaminants concentration in the influent were achieved at 50%
      carrier filling ratio. The Haldane competitive substrate inhibition kinetics
      model was used to describe the relationship between the oxygen uptake rate of
      ammonium oxidizers and the concentration of free ammonium. The highest biofilm
      microbial community functional diversity (Shannon's diversity index, H') and
      evenness (Shannon's evenness index, E') were obtained at 50% carrier filling
      ratio in all runs using a Biolog ECO microplate. 

PMID- 24907567
TI  - Multi-Gaussian-DAEM-reaction model for thermal decompositions of cellulose,
      hemicellulose and lignin: comparison of N2 and CO2 atmosphere.
AB  - Thermal decompositions of three components of biomass (cellulose, hemicellulose
      and lignin) were studied using nonisothermal thermogravimetric analysis (TGA)
      under both oxidative and inert atmospheres at a heating rate of 10 K min(-1). The
      multi-Gaussian-distributed activation energy model (DAEM)-reaction model was
      first developed to describe thermal decomposition behaviors of three components.
      Results showed that the presence of CO2 enhanced the thermal decompositions of
      three components in high temperature range, but made little difference in low
      temperature range. Decomposition behaviors under CO2 were analyzed by the two
      stage reaction mechanism corresponding to the pyrolysis process of original
      materials and the gasification process of char. During gasification stage, CO2
      was reduced to CO, which provided a possibility of a reduction in greenhouse gas
      emissions. In addition, more CO was produced, and therefore the thermal value of
      gas was improved. The findings imply that CO2 gasification technology of biomass
      has great research significance.

PMID- 24907569
TI  - Effect of phenol on the nitrogen removal performance and microbial community
      structure and composition of an anammox reactor.
AB  - The effects of phenol on the nitrogen removal performance of a sequencing batch
      reactor (SBR) with anammox activity and on the microbial community within the
      reactor were evaluated. A phenol concentration of 300 mg L(-1) reduced the
      ammonium-nitrogen removal efficiency of the SBR from 96.5% to 47%. The addition
      of phenol changed the microbial community structure and composition considerably,
      as shown by denaturing gradient gel electrophoresis and 454 pyrosequencing of 16S
      rRNA genes. Some phyla, such as Proteobacteria, Verrucomicrobia, and Firmicutes,
      increased in abundance, whereas others, such as Acidobacteria, Chloroflexi,
      Planctomycetes, GN04, WS3, and NKB19, decreased. The diversity of the anammox
      bacteria was also affected by phenol: sequences related to Candidatus Brocadia
      fulgida were no longer detected, whereas sequences related to Ca. Brocadia sp. 40
      and Ca. Jettenia asiatica persisted. These results indicate that phenol adversely
      affects anammox metabolism and changes the bacterial community within the anammox
      reactor.

PMID- 24907570
TI  - Aerobic stabilization of biological sludge characterized by an extremely low
      decay rate: modeling, identifiability analysis and parameter estimation.
AB  - Aerobic digestion batch tests were run on a sludge model that contained only two
      fractions, the heterotrophic biomass (XH) and its endogenous residue (XP). The
      objective was to describe the stabilization of the sludge and estimate the
      endogenous decay parameters. Modeling was performed with Aquasim, based on long
      term data of volatile suspended solids and chemical oxygen demand (VSS, COD).
      Sensitivity analyses were carried out to determine the conditions for unique
      identifiability of the parameters. Importantly, it was found that the COD/VSS
      ratio of the endogenous residues (1.06) was significantly lower than for the
      active biomass fraction (1.48). The decay rate constant of the studied sludge
      (low bH, 0.025 d(-1)) was one-tenth that usually observed (0.2d(-1)), which has
      two main practical significances. Digestion time required is much more long; also
      the oxygen uptake rate might be <1.5 mg O2/gTSSh (biosolids standards), without
      there being significant decline in the biomass.

PMID- 24907568
TI  - Vermicomposting of Tea Factory Coal Ash: metal accumulation and metallothionein
      response in Eisenia fetida (Savigny) and Lampito mauritii (Kinberg).
AB  - Earthworms can accumulate heavy metals in their intestines to a great extent.
      Impact of feed materials and duration of metal exposure on natural activity of
      earthworms are rather unclear; this investigation therefore addresses the impact
      of metal rich Tea Factory Coal Ash (TFCA) on reproduction, composting and metal
      accumulation ability of Eisenia fetida and Lampito mauritii. Earthworm count and
      cocoon production increased significantly during vermicomposting. pH of the
      vermicomposted mixtures shifted toward neutrality, total organic C decreased
      substantially and total N enhanced significantly compared to composting. High
      heavy metal (Mn, Zn, Cu, As) accumulation was recorded in the intestine of both
      the earthworm species. Moreover, gradual increase in the metal-inducible
      metallothionein concentration indicated the causal mechanism of metal
      accumulation in these species. TFCA+cow dung (CD) (1:1) were most favorable feed
      mixture for E. fetida and TFCA+CD (1:2) were good for L. mauritii in regard to
      metal accumulation and compost quality. 

PMID- 24907571
TI  - Influence of feedstock chemical composition on product formation and
      characteristics derived from the hydrothermal carbonization of mixed feedstocks.
AB  - As the exploration of the carbonization of mixed feedstocks continues, there is a
      distinct need to understand how feedstock chemical composition and structural
      complexity influence the composition of generated products. Laboratory
      experiments were conducted to evaluate the carbonization of pure compounds,
      mixtures of the pure compounds, and complex feedstocks comprised of the pure
      compounds (e.g., paper, wood). Results indicate that feedstock properties do
      influence carbonization product properties. Carbonization product characteristics
      were predicted using results from the carbonization of the pure compounds and
      indicate that recovered solids energy contents are more accurately predicted than
      solid yields and the carbon mass in each phase, while predictions associated with
      solids surface functional groups are more difficult to predict using this linear
      approach. To more accurately predict carbonization products, it may be necessary
      to account for feedstock structure and/or additional feedstock properties. 

PMID- 24907572
TI  - Antibacterial and enzymatic activity of microbial community during wastewater
      treatment by pilot scale vermifiltration system.
AB  - The present study investigated microbial community diversity and antibacterial
      and enzymatic properties of microorganisms in a pilot-scale vermifiltration
      system during domestic wastewater treatment. The study included isolation and
      identification of diverse microbial community by culture-dependent method from a
      vermifilter (VF) with earthworms and a conventional geofilter (GF) without
      earthworms. The results of the four months study revealed that presence of
      earthworms in VF could efficiently remove biochemical oxygen demand (BOD),
      chemical oxygen demand (COD), total and fecal coliforms, fecal streptococci and
      other pathogens. Furthermore, the burrowing activity of earthworms promoted the
      aeration conditions in VF which led to the predominance of the aerobic
      microorganisms, accounting for complex microbial community diversity.
      Antibacterial activity of the isolated microorganisms revealed the mechanism
      behind the removal of pathogens, which is reported for the first time.
      Specifically, cellulase, amylase and protease activity is responsible for
      biodegradation and stabilization of organic matter. 

PMID- 24907573
TI  - Utilization of coffee by-products obtained from semi-washed process for
      production of value-added compounds.
AB  - The semi-dry processing of coffee generates significant amounts of coffee pulp
      and wastewater. This study evaluated the production of bioethanol and volatile
      compounds of eight yeast strains cultivated in a mixture of these residues.
      Hanseniaspora uvarum UFLA CAF76 showed the best fermentation performance; hence
      it was selected to evaluate different culture medium compositions and inoculum
      size. The best results were obtained with 12% w/v of coffee pulp, 1 g/L of yeast
      extract and 0.3 g/L of inoculum. Using these conditions, fermentation in 1 L of
      medium was carried out, achieving higher ethanol yield, productivity and
      efficiency with values of 0.48 g/g, 0.55 g/L h and 94.11% respectively. Twenty
      one volatile compounds corresponding to higher alcohols, acetates, terpenes,
      aldehydes and volatile acids were identified by GC-FID. Such results indicate
      that coffee residues show an excellent potential as substrates for production of
      value-added compounds. H. uvarum demonstrated high fermentative capacity using
      these residues.

PMID- 24907574
TI  - Where does the removal of H2S from biogas occur in microaerobic reactors?
AB  - In order to maximise the efficiency of biogas desulphurisation and reduce the
      oxygen cost during microaerobic digestion, it is essential to know how the
      process occurs. For this purpose, a reactor with a total volume of 266 L,
      treating 10 L/d of sewage sludge, was operated with 25.0 L and without headspace.
      Under anaerobic conditions, the H2S concentration in the biogas varied between
      0.21 and 0.38%v/v. Next, O2 was supplied from the bottom of the reactor. At 0.25
      0.30 NLO2/Lfed, the biogas was entirely desulphurised, and its O2 content
      remained below 1.03%v/v, when the digester had 25.0 L of gas space. However, with
      almost no headspace, the H2S content in the biogas fluctuated from 0.08 to
      0.21%v/v, while the average O2 concentration was 1.66%v/v. The removed H2S
      accumulated in the outlet pipe of the biogas in the form of S(0) due to the
      insufficient headspace.

PMID- 24907575
TI  - Kinetics modeling predicts bioaugmentation with Sphingomonad cultures as a viable
      technology for enhanced pharmaceutical and personal care products removal during
      wastewater treatment.
AB  - Pharmaceutical and personal care products (PPCPs) discharged with wastewater
      treatment effluents are a surface water quality concern. PPCPs are partially
      removed during wastewater treatment and biological transformation is an important
      removal mechanism. To investigate the potential for enhanced PPCP removal using
      bioaugmentation, bacteria were previously isolated from activated sludge capable
      of degrading PPCPs to ng/L concentrations. This study examined the degradation
      kinetics of triclosan and bisphenol A by five of these bacteria, both in pure
      culture and when augmented to activated sludge. Sorption coefficients were
      determined to account for the influence of partitioning during bioremoval. When
      the bacteria were added to activated sludge, degradation increased.
      Experimentally determined kinetic parameters were used to model a full-scale
      continuous treatment process, showing that low biomass could achieve reduced
      effluent PPCP concentrations. These results demonstrated that bioaugmentation may
      improve PPCP removal using established wastewater infrastructure under conditions
      of high solids partitioning. 

PMID- 24907576
TI  - Mesophilic co-digestion of dairy manure and lipid rich solid slaughterhouse
      wastes: process efficiency, limitations and floating granules formation.
AB  - Lipid and protein rich solid slaughterhouse wastes are attractive co-substrates
      to increase volumetric biogas production in co-digestion with dairy manure.
      Addition of decanter sludge (DS), containing 42.2% of lipids and 35.8% of
      proteins (total solids basis), up to 5% of feed mixture resulted in a stable
      process without any indication of long chain fatty acids (LCFA) or free ammonia
      (NH3) inhibition and in 3.5-fold increase of volumetric biogas production.
      Contrary, only lipids addition as technical fat (TF) at over 2% of feed mixture
      resulted in formation of floating granules (FG) and process efficiency decrease.
      Formed FG had low biodegradability and its organic part was composed of lipids
      and calcium salts of LCFAs. Anaerobic digestion process intentionally directed to
      FG formation, could be a viable option for mitigation and control of lipids
      overload and derived LCFA inhibition. 

PMID- 24907577
TI  - Heterogeneous catalytic ozonation of biologically pretreated Lurgi coal
      gasification wastewater using sewage sludge based activated carbon supported
      manganese and ferric oxides as catalysts.
AB  - Sewage sludge of biological wastewater treatment plant was converted into sewage
      sludge based activated carbon (SBAC) with ZnCl2 as activation agent, which
      supported manganese and ferric oxides as catalysts (including SBAC) to improve
      the performance of ozonation of real biologically pretreated Lurgi coal
      gasification wastewater. The results indicated catalytic ozonation with the
      prepared catalysts significantly enhanced performance of pollutants removal and
      the treated wastewater was more biodegradable and less toxic than that in
      ozonation alone. On the basis of positive effect of higher pH and significant
      inhibition of radical scavengers in catalytic ozonation, it was deduced that the
      enhancement of catalytic activity was responsible for generating hydroxyl
      radicals and the possible reaction pathway was proposed. Moreover, the prepared
      catalysts showed superior stability and most of toxic and refractory compounds
      were eliminated at successive catalytic ozonation runs. Thus, the process with
      economical, efficient and sustainable advantages was beneficial to engineering
      application.

PMID- 24907578
TI  - Effects of hydrothermal pretreatment of sugar beet pulp for methane production.
AB  - The effect of Liquid Hot Water treatment conditions on the degree of sugar beet
      pulp (SBP) degradation was studied. The SBP was subjected to hydrothermal
      processing at temperatures ranging from 120 to 200  degrees C. The relationship
      between processing temperature and parameters of liquid and solid fractions of
      resulting hydrolysates as well as the efficiency of their methane fermentation
      was determined. The highest concentration of free glucose (3.29 mg ml(-1)) was
      observed when the hydrolysis was conducted at 160  degrees C (it was 4-fold
      higher than that after processing at 120  degrees C). Total acids and aldehydes
      concentrations in the liquid fractions were increased from 0.005 mg ml(-1) for
      the untreated SBP to 1.61 mg ml(-1) after its processing at 200  degrees C.
      Parameters of the hydrolysates obtained by the LHW treatment decided of the
      efficiency of methane fermentation. The highest cumulative methane yield (502.50
      L CH4 kg(-1)VS) was obtained from the sugar beet pulp hydrolysate produced at 160
      degrees C.

PMID- 24907579
TI  - Production of poly(hydroxybutyrate-hydroxyvalerate) from waste organics by the
      two-stage process: focus on the intermediate volatile fatty acids.
AB  - The two-stage process, coupling volatile fatty acids (VFAs) fermentation and
      poly(hydroxybutyrate-hydroxyvalerate) (P(HB/HV)) biosynthesis, was investigated
      for five waste organic materials. The overall conversion efficiencies were
      glycerol>starch>molasses>waste sludge>protein, meanwhile the maximum P(HB/HV)
      (1.674 g/L) was obtained from waste starch. Altering the waste type brought more
      effects on VFAs composition other than the yield in the first stage, which in
      turn greatly changed the yield in the second stage. Further study showed that
      even-number carbon VFAs (or odd-number ones) had a good positive linear
      relationship with P(HB/HV) content of HB (or HV). Additionally, VFA producing
      microbiota was analyzed by pyrosequencing methods for five wastes, which
      indicated that specific species (e.g., Lactobacillus for protein; Ethanoligenens
      for starch; Ruminococcus and Limnobacter for glycerol) were dominant in the
      community for VFAs production. Potential competition among acidogenic bacteria
      specially involved to produce some VFA was proposed as well.

PMID- 24907580
TI  - Processing anaerobic sludge for extended storage as anaerobic digester inoculum.
AB  - Thermophilic anaerobic sludge was processed to reduce the volume and moisture
      content in order to reduce costs for storing and transporting the sludge as
      microbial inoculum for anaerobic digester startup. The moisture content of the
      sludge was reduced from 98.7% to 82.0% via centrifugation and further to 71.5%
      via vacuum evaporation. The processed sludge was stored for 2 and 4 months and
      compared with the fresh sludge for the biogas and methane production using food
      waste and non-fat dry milk as substrates. It was found that fresh unprocessed
      sludge had the highest methane yield and the yields of both unprocessed and
      processed sludges decreased during storage by 1-34%, however processed sludges
      seemed to regain some activity after 4 months of storage as compared to samples
      stored for only 2 months. Maximum methane production rates obtained from modified
      Gompertz model application also increased between the 2-month and 4-month
      processed samples.

PMID- 24907581
TI  - Sulfobetaine-based polymer brushes in marine environment: is there an effect of
      the polymerizable group on the antifouling performance?
AB  - Three different zwitterionic polymer brush coatings for marine biofouling control
      were prepared by surface-initiated atom transfer radical polymerization (ATRP) of
      sulfobetaine-based monomers including methacrylamide (SBMAm), vinylbenzene (SBVB)
      and vinylimidazolium (SBVI). None of these brush systems have been assessed
      regarding marine antifouling performance. Antifouling tests performed indicate
      that surfaces featuring these three brush systems substantially reduce the
      adhesion of the marine microalgae, Amphora coffeaeformis, and the settlement of
      cyprid larvae of the barnacle, Amphibalanus amphitrite, in a similar way,
      displaying comparable performance. Thus, it appears that the chemical structure
      of the polymerizable group has no substantial influence on marine antifouling
      performance. 

PMID- 24907582
TI  - Release and antibacterial activity of allyl isothiocyanate/beta-cyclodextrin
      complex encapsulated in electrospun nanofibers.
AB  - Allyl isothiocyanate (AITC) is known as an efficient antibacterial agent but it
      has a very high volatility. Herein, AITC and AITC/beta-cyclodextrin (CD)
      inclusion complex (IC) incorporated in polyvinyl alcohol (PVA) nanofibers were
      produced via electrospinning. SEM images elucidated that incorporation of AITC
      and AITC/beta-CD-IC into polymer matrix did not affect the bead-free fiber
      morphology of PVA nanofibers. (1)H-NMR and headspace GC-MS analyses revealed that
      very low amount of AITC was remained in PVA/AITC-NF because of the rapid
      evaporation of AITC during the electrospinning process. Nevertheless, much higher
      amount of AITC was preserved in the PVA/AITC/beta-CD-IC-NF due to the CD
      inclusion complexation. The sustained release of AITC from nanofibers was
      evaluated at 30 degrees C, 50 degrees C and 75 degrees C via headspace GC-MS.
      When compared to PVA/AITC-NF, PVA/AITC/beta-CD-IC-NF has shown higher
      antibacterial activity against Escherichia coli and Staphylococcus aureus due to
      the presence of higher amount of AITC in this sample which was preserved by CD
      IC. 

PMID- 24907583
TI  - Folic acid-conjugated iron oxide porous nanorods loaded with doxorubicin for
      targeted drug delivery.
AB  - Iron oxide porous nanorods (IOPNR) with lengths ranging from 40nm to 60nm and
      pore diameters ranging from 5nm to 10nm were prepared, and further modified with
      NH2-PEG-FA (FA-PEG-IOPNR) for ligand targeting and modified with NH2-PEG-OCH3
      (PEG-IOPNR) as a control. Instead of chemical bonding, doxorubicin (DOX), a low
      water solubility anticancer drug, was loaded in the pores of the modified IOPNR
      because of their porous structure and high porosity. The release of DOX in acidic
      PBS solution (pH 5.3) was faster than that in neutral (pH 7.4) solution. The
      analysis results from TEM, inductively coupled plasma emission spectroscopy,
      confocal laser scanning microscopy, and flow cytometry analyses indicated that
      the presence of FA on the surface of the nanorods increase the cellular uptake of
      nanorods in the case of HeLa cells, a folate receptor (FR)-positive cell line. In
      contrast, for COS 7 cells, a FR-negative cell line, FA ligand on the surface of
      the nanorods showed no effect on the cellular uptake. MTT assay indicated that
      the cytotoxicity of DOX loaded in FA-PEG-IOPNR to HeLa cells was higher than that
      of DOX in PEG-IOPNR. In the case of COS 7 cells, no significant difference
      between the cytotoxicity of DOX loaded in FA-PEG-IOPNR and PEG-IOPNR was found.
      These results suggested that FA-PEG-IOPNR had the potential for target delivery
      of chemotherapeutic into cancer cells. 

PMID- 24907584
TI  - Interactions of serum with polyelectrolyte-stabilized liposomes: Cryo-TEM
      studies.
AB  - Liposomes are used for in vitro or in vivo vectorization of drugs, proteins, or
      nucleic acids. However, the main problem with the application of liposomes for
      this purpose is their low stability in contact with blood serum. In this article,
      interactions between the whole serum and anionic liposomes, both bare and covered
      with strong polycations, were studied. The polycations of different chemical
      structures were prepared by the modification of poly(allylamine hydrochloride)
      (PAH). Dynamic light scattering (DLS), zeta potential and transmission cryo
      electron microscopy (cryo-TEM) measurements showed that the adsorption of the
      polycations on the anionic liposomes induced a reversible aggregation of
      vesicles. The stable isolated polyelectrolyte-covered vesicles were obtained
      after the addition of sufficient amounts of the polycations. The effect of full
      serum on the morphology and stability of the polycation-coated liposomes was
      studied using cryo-TEM and a fluorescence method. The cryo-TEM analysis revealed
      that the introduction of serum caused the osmotic-driven destabilization of the
      bare liposomes or formation of twinned vesicles. Due to these processes the
      liposomes lost most of their content immediately after serum addition. The
      polycation-covered liposomes showed improved stability in the presence of serum.
      Partial deflation of the vesicles was observed, however, the loss of the content
      was significantly limited. The effect of the polymer structure, especially the
      position of the charged groups with respect to the main polymer backbone, on the
      stabilization of the polycation-covered liposomes in the presence of serum was
      discussed. 

PMID- 24907585
TI  - Cationic vesicles based on biocompatible diacyl glycerol-arginine surfactants:
      physicochemical properties, antimicrobial activity, encapsulation efficiency and
      drug release.
AB  - Physicochemical characteristics of cationic vesicular systems prepared from
      biocompatible diacyl glycerol-arginine surfactants are investigated. These
      systems form stable cationic vesicles by themselves and the average diameter of
      the vesicles decreases as the alkyl chain length of the surfactant increases. The
      addition of DPPC also modifies the physicochemical properties of these vesicles.
      Among the drugs these cationic formulations can encapsulate, we have considered
      Ciprofloxacin and 5-Fluorouracil (5-FU). We show that the percentage of
      encapsulated drug depends on both the physicochemical properties of the carrier
      and the type of drug. The capacity of these systems to carry different molecules
      was evaluated performing in vitro drug release studies. Finally, the
      antimicrobial activity of empty and Ciprofloxacin-loaded vesicles against Gram
      positive and Gram-negative bacteria has been determined. Three bacteria were
      tested: Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. The in
      vitro drug release from all formulations was effectively delayed. Empty cationic
      vesicles showed antimicrobial activity and Ciprofloxacin-loaded vesicles showed
      similar or higher antimicrobial activity than the free drug solution. These
      results suggest that our formulations represent a great innovation in the
      pharmaceutical field, due to their dual pharmacological function: one related to
      the nature of the vehiculated drug and the other related to the innate
      antibacterial properties of the surfactant-based carriers. 

PMID- 24907586
TI  - NADPH oxidase mediates TNF-alpha-evoked in vitro brain barrier dysfunction: roles
      of apoptosis and time.
AB  - The pro-inflammatory cytokine TNF-alpha severely perturbs the integrity of the
      blood-brain barrier (BBB). This study explored the specific roles of NADPH
      oxidase and associated downstream effectors by using human brain microvascular
      endothelial cells (HBMECs) and human astrocytes (HAs), the key components of BBB,
      alone or in co-cultures to mimic human BBB. Exposure to TNF-alpha (6h) impaired
      BBB integrity as evidenced by marked decreases in transendothelial electrical
      resistance and concurrent increases in paracellular flux which appeared to
      subside with time (24h). Increased barrier dysfunction concurred with increases
      in endothelial NADPH oxidase activity, O2(-) production, actin stress fibre
      formation, MMP-2/9 activities and concomitant decreases in antioxidant (CuZn-SOD
      and catalase) and tight junction (claudin-5 and occludin) protein expressions.
      Conversely, TNF-alpha did not affect astrocytic MMP activities and antioxidant
      enzyme expressions. Unlike BBB damage, rates of HBMEC and HA apoptosis increased
      by time. Suppression of NADPH oxidase by apocynin or diphenyleneiodonium
      prevented TNF-alpha-evoked morphological changes and apoptosis, attenuated
      endothelial MMP activity and helped retain usual tight junction protein
      expression and barrier function. In conclusion, HBMECs constitute the main source
      of oxidative stress and basement-membrane degrading endopeptidases in
      inflammatory conditions associated with excessive release of TNF-alpha where
      targeting NADPH oxidase may prove extremely beneficial in maintaining proper
      barrier activity through prevention of cytoskeletal and tight junction
      reorganisations.

PMID- 24907588
TI  - Reinforcing and neural activating effects of norharmane, a non-nicotine tobacco
      constituent, alone and in combination with nicotine.
AB  - Tobacco use is the leading cause of preventable death. Although the health risks
      are well known, cessation rates remain low. Whereas behavioral and
      neuroanatomical studies on tobacco addiction conventionally use nicotine, there
      is evidence that other constituents, such as monoamine oxidase inhibitors, may be
      important factors for modeling smoking. The aims of the present study were
      therefore to determine whether norharmane, a tobacco constituent and monoamine
      oxidase inhibitor, is self-administered alone and/or in combination with
      nicotine, and to evaluate the neural mechanisms underlying acquisition of self
      administration of the two drugs. Sprague-Dawley rats were catheterized and
      allowed to intravenously self-administer either saline, nicotine (7.5
      MUg/kg/inj), norharmane (0.25 or 2.5 MUg/kg/inj), alone or combined together
      (7.5+2.5 MUg/kg/inj) for five days at fixed ratio (FR)1, two days each at FR2 and
      FR5, and one day at progressive ratio. Animals acquired self-administration of
      norharmane alone (2.5 MUg/kg/inj), and the reinforcing effects of nicotine and
      norharmane were additive. For neuroanatomical analyses, rats self-administered
      the same treatments for six days at FR1, then brains were collected and processed
      by in situ hybridization for cfos mRNA expression. Treatment-specific profiles of
      regional cfos expression and correlations between cfos mRNA levels and behavioral
      responding were observed. Thus, not only was norharmane behaviorally reinforcing
      but, when combined with nicotine, resulted in patterns of neural activation
      distinct from that of norharmane or nicotine alone. This suggests that non
      nicotine constituents can have central activating effects independent of
      nicotine, further substantiating the need for their inclusion in preclinical
      investigations of tobacco dependence.

PMID- 24907587
TI  - Adenosine through the A2A adenosine receptor increases IL-1beta in the brain
      contributing to anxiety.
AB  - Anxiety is one of the most commonly reported psychiatric conditions, but its
      pathogenesis is poorly understood. Ailments associated with activation of the
      innate immune system, however, are increasingly linked to anxiety disorders. In
      adult male mice, we found that adenosine doubled caspase-1 activity in brain by a
      pathway reliant on ATP-sensitive potassium (KATP) channels, protein kinase A
      (PKA) and the A2A adenosine receptor (AR). In addition, adenosine-dependent
      activation of caspase-1 increased interleukin (IL)-1beta in the brain by 2-fold.
      Peripheral administration of adenosine in wild-type (WT) mice led to a 2.3-fold
      increase in caspase-1 activity in the amygdala and to a 33% and 42% reduction in
      spontaneous locomotor activity and food intake, respectively, that were not
      observed in caspase-1 knockout (KO), IL-1 receptor type 1 (IL-1R1) KO and A2A AR
      KO mice or in mice administered a caspase-1 inhibitor centrally. Finally,
      adenosine administration increased anxiety-like behaviors in WT mice by 28% in
      the open field test and by 55% in the elevated zero-maze. Caspase-1 KO mice, IL
      1R1 KO mice, A2A AR KO mice and WT mice treated with the KATP channel blocker,
      glyburide, were resistant to adenosine-induced anxiety-like behaviors. Thus, our
      results indicate that adenosine can act as an anxiogenic by activating caspase-1
      and increasing IL-1beta in the brain. 

PMID- 24907589
TI  - Mouse social stress induces increased fear conditioning, helplessness and fatigue
      to physical challenge together with markers of altered immune and dopamine
      function.
AB  - In neuropsychiatry, animal studies demonstrating causal effects of environmental
      manipulations relevant to human aetiology on behaviours relevant to human
      psychopathologies are valuable. Such valid models can improve understanding of
      aetio-pathophysiology and preclinical discovery and development of new
      treatments. In depression, specific uncontrollable stressful life events are
      major aetiological factors, and subsequent generalized increases in fearfulness,
      helplessness and fatigue are core symptoms or features. Here we exposed adult
      male C57BL/6 mice to 15-day psychosocial stress with loss of social control but
      minimal physical wounding. One cohort was assessed in a 3-day test paradigm of
      motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18,
      and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and
      29, followed by the 3-day paradigm on days 30-32. All tests used a physical
      aversive stimulus, namely mild, brief electroshocks. Socially stressed mice
      displayed decreased motor activity, increased fear acquisition, decreased 2-way
      avoid-escape responding (increased helplessness) and increased fatigue. They also
      displayed increased plasma TNF and spleen hypertrophy, and adrenal hypertrophy
      without hyper-corticoidism. In a third cohort, psychosocial stress effects on
      brain gene expression were assessed using next generation sequencing. Gene
      expression was altered in pathways of inflammation and G-protein coupled
      receptors in prefrontal cortex and amygdala; in the latter, expression of genes
      important in dopamine function were de-regulated including down-regulated Drd2,
      Adora2a and Darpp-32. This model can be applied to identify targets for treating
      psychopathologies such as helplessness or fatigue, and to screen
      compounds/biologics developed to act at these targets. 

PMID- 24907591
TI  - Latent variable analysis indicates that seasonal anisotropy accounts for the
      higher prevalence of left-handedness in men.
AB  - According to the Geschwind-Galaburda theory of cerebral lateralization, high
      intrauterine testosterone levels delay left brain hemisphere maturation and thus
      promote left-handedness. Human circulating testosterone levels are higher in the
      male fetus and also vary with length of photoperiod. Therefore, a higher
      prevalence of left-handedness, coupled with seasonal anisotropy (i.e., a non
      uniform distribution of handedness across birth months or seasons), may be
      expected among men. Prior studies yielded inconsistent evidence for seasonal
      anisotropy and suffered from confounding and a number of shortcomings affecting
      statistical power. This study examined hand preference and associations of
      handedness with sex, age, and season of birth in independent discovery (n = 7658)
      and replication (n = 5062) samples from Central Europe with latent class analysis
      (LCA). We found clear evidence of a surplus of left-handed men born during the
      period November-January, which is consistent with predictions from the Geschwind
      Galaburda theory. Moreover, seasonal anisotropy fully accounted for the higher
      prevalence of left-handedness among men, relative to women. Implications of these
      findings with regard to seasonal anisotropy research and handedness assessment
      and classification are discussed. 

PMID- 24907590
TI  - Differential effects of NMDA receptor antagonists at lower and higher doses on
      basal gamma band oscillation power in rat cortical electroencephalograms.
AB  - Schizophrenic patients have been shown to exhibit abnormal cortical gamma band
      oscillation (GBO), which is thought to be related to the symptoms of
      schizophrenia, including cognitive impairment. Recently, non-competitive NMDA
      receptor (NMDAr) antagonists such as MK-801 and ketamine have been reported to
      increase the basal GBO power in rat cortical electroencephalograms. However, the
      mechanisms underlying the increase in basal GBO power induced by non-competitive
      NMDAr antagonists remain unclear. In the present study, we characterized the non
      competitive NMDAr antagonists-increased GBO (30-80 Hz) power. MK-801 (0.05-0.2
      mg/kg) increased the GBO power, exhibiting an inverted U-shape dose-response
      curve; at higher doses (0.3-1 mg/kg), the increase in GBO was reversed. The GBO
      power was closely correlated with the high-frequency oscillation (130-180 Hz)
      power following MK-801 administration, while the GBO power was inversely
      correlated with the increase in delta oscillation (0.5-4 Hz) power at higher
      doses. PCP (1.25-10 mg/kg) and ketamine (2.5-30 mg/kg) also exhibited the
      inverted U-shape dose-responses for the basal GBO power similar to MK-801.
      Interestingly, memantine (10-30 mg/kg) dose-dependently and potently increased
      the GBO power without remarkably affecting the other frequency band. In contrast,
      other psychotomimetics, such as methamphetamine (1-10 mg/kg) and DOI (0.5-2
      mg/kg), did not induce noticeable changes in the basal GBO power even at doses
      that induce abnormal behaviors, indicating that the increase in GBO power induced
      by NMDAr antagonists is not necessarily attributed to psychotomimetic effects. In
      conclusion, the basal GBO power increase in response to non-competitive NMDAr
      antagonists may reflect the cortical hyperglutamatergic state through GABAergic
      disinhibition. 

PMID- 24907592
TI  - Ethical implications of resource-limited evaluations: lessons from an INGO in the
      eastern Democratic Republic of Congo.
AB  - The emphasis on demonstrable program results in international development work
      has produced countless evaluation guidelines and numerous scholars have
      championed specific, ethical-based evaluation approaches to guide international
      nongovernmental organizations (INGOs). Yet few studies have examined the ethical
      implications of current evaluation practices among INGOs or the resulting effects
      on INGO-funded programs. This article focuses on one among a growing population
      of young, U.S.-based INGOs whose evaluation practices reflect limitations of
      time, methodological expertise and funding. Drawing on existing principles of
      ethical evaluations, the author explores the circumstances and potential
      implications of one evaluation performed by an INGO in the eastern Democratic
      Republic of Congo and concludes that an ethically defensible evaluation exceeds
      the capacity of this young INGO. Four propositions are forwarded to highlight the
      tensions between currently accepted evaluation guidelines and INGO realities.
      Finally, to help under-resourced INGOs minimize the potential ethical
      implications for their programs, the article recommends that they prioritize
      their limited resources to: (1) build local capacity and decentralize evaluation
      tasks and responsibilities; (2) share program agendas and solicit feedback on
      implementation from evaluands; (3) share field impressions with local and expert
      stakeholders; and, (4) translate communications into local dialects to facilitate
      discussion about structuring future programs and their evaluation. 

PMID- 24907593
TI  - Insights into public export promotion programs in an emerging economy: the case
      of Malaysian SMEs.
AB  - This study evaluates the impact of public export promotion programs (EPPs) among
      small and medium-sized enterprises (SMEs) in Malaysia. Three indicators, level of
      awareness, frequency of use, and perception of usefulness, were examined
      according to a firm's export status. The global evaluation suggests that
      exporters are more frequent users of EPPs and perceive them to be more useful
      than non-exporters. Nonetheless, both groups demonstrate higher levels of
      awareness, are frequent users, and perceive the programs relating to export
      info/knowledge are more usefulness than programs relating to financial
      assistance. Further analysis also reveals that the frequency of use and the
      perception of usefulness for most programs are positively related to export
      experience, but not to export turnover. This study offers insights into the
      effectiveness of export programs for encouraging export initiation and expansion
      in an emerging economy. 

PMID- 24907594
TI  - Medical students and the electronic health record: 'an epic use of time'.

PMID- 24907595
TI  - Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for
      drug delivery to the inner ear.
AB  - Intratympanic glucocorticoid therapy aims to reduce the side effects associated
      with systemic long-time therapy of inner ear diseases or traumata after cochlear
      implantation. For that purpose, thermoreversible hydrogels being fluid at room
      temperature but solid at body temperature are known to be appropriate drug
      delivery systems. In this work, the two key parameters sol-gel transition time
      and temperature of Poloxamer 407 (POX 407) based hydrogels containing oto
      compatible micronized triamcinolone acetonide (TAAc) were evaluated by
      rheological experiments varying the concentrations of the different compounds. A
      20% POX 407 hydrogel in PBS containing 30% TAAc emerged as the most appropriate
      formulation. Oscillation-rotation-oscillation studies at two temperature levels
      were found to be an useful in-vitro test system for the hydrogel which revealed
      sufficient storage stability at 4  degrees C, injectability of the sol,
      solidification within 20s at body temperature and persistent stiffness indicating
      prolonged adhesion at the round window membrane. According to the in-vitro
      release studies using the TranswellTM system, absorption of the poor water
      soluble TAAc is partly due to the low amount of dissolved drug but predominantly
      due to micellar transport resulting in a cumulative release of 262.6+/-13.4 MUg
      TAAc within one week followed by a sustained release of 193.1+/-8.3 MUg TAAc
      within the next three weeks. Thus, the formation of POX 407 micelles is the basis
      not only for gel formation but also absorptivity of TAAc. All in all, fine tuned
      rheological experiments and absorption studies emerged as useful tools for
      preclinical evaluation of intratympanally administered hydrogels.

PMID- 24907596
TI  - Comparison of ethosomes and liposomes for skin delivery of psoralen for psoriasis
      therapy.
AB  - Recent reports have indicated that psoriasis may be caused by malfunctioning
      dermal immune cells, and psoralen ultraviolet A (PUVA) is an effective treatment
      for this chronic disease. However, conventional topical formulations achieve poor
      drug delivery across patches of psoriasis to their target sites. The present
      study describes the development of a novel psoralen transdermal delivery system
      employing ethosomes, flexible vesicles that can penetrate the stratum corneum and
      target deep skin layers. An in vitro skin permeation study showed that the
      permeability of psoralen-loaded ethosomes was superior to that of liposomes.
      Using ethosomes, psoralen transdermal flux and skin deposition were 38.89+/-0.32
      MUg/cm(2)/h and 3.87+/-1.74 MUg/cm(2), respectively, 3.50 and 2.15 times those
      achieved using liposomes, respectively. The ethosomes and liposomes were found to
      be safe following daily application to rat skin in vivo, for 7 days. The
      ethosomes showed better biocompatibility with human embryonic skin fibroblasts
      than did an equivalent ethanol solution, indicating that the phosphatidylcholine
      present in ethosome vesicles improved their biocompatibility. These findings
      indicated that ethosomes could potentially improve the dermal and transdermal
      delivery of psoralen and possibly of other drugs requiring deep skin delivery.

PMID- 24907597
TI  - Synthesis and evaluation of sodium deoxycholate sulfate as a lipid drug carrier
      to enhance the solubility, stability and safety of an amphotericin B inhalation
      formulation.
AB  - Amphotericin B (AmB) is still used as the gold standard for therapy against
      invasive fungal diseases. However, the use of AmB through oral administration is
      restricted due to its low solubility and stability in aqueous solution, which is
      the cause for its poor bioavailability and highly varying absorption. Therefore,
      an attempt has been made to enhance the solubility and stability of AmB to
      evaluate its bioactivity and safety for use as an inhaler by using a new
      excipient sodium deoxycholate sulfate (SDS) with aim of using it as a drug
      carrier for AmB. Therefore, SDS was formulated together with AmB as a dry powder
      by lyophilization. The dry powder was reconstituted in distilled water and
      evaluated its physicochemical properties such as zeta potential, particle size
      and pH to compare its solubility and stability of the formulations with a SDC-AmB
      (i.e., known as Fungizone((r))). In vitro toxicity studies were carried out with
      red blood cells (RBC) and respiratory cell lines. Bioactivity was determined by a
      micro-dilution method against Candidaalbicans and Cryptococcusneoformans. We
      found that SDS-AmB had a zeta potential (-45.53 mV), which was higher than of
      Fungizone((r)); and produced a stable particle size in solution (73.8 nm). The
      particle size distributions of both formulations were expressed as their mass
      median aerodynamic diameters (MMAD; 1.70 and 1.74 MUm), their fine particle
      fractions (FPF; 70 and 80%) and geometric standard deviations (GSD; 2.3 and 2.0),
      respectively. These values indicated that the sizes were appropriate for use in
      an inhaler. Pure AmB was found to hemolyse RBC and was very toxic to alveolar
      macrophage cells, as their viability rapidly declined from 93 to 56% when the AmB
      concentration increased from 1 to 8 MUg/mL. The SDS-AmB formulation had a
      significantly reduced toxicity compared to AmB. The results clearly indicated
      that the SDS-lipid based nanoparticles had the potential to be used as an
      alternative option to Fungizone((r)) for an AmB formulation for inhalation.

PMID- 24907598
TI  - A PAT approach for the on-line monitoring of pharmaceutical co-crystals formation
      with near infrared spectroscopy.
AB  - Cocrystals represent a class of crystalline solids consisting of two or more
      molecular species usually held together by non-covalent bonds. Pharmaceutical
      cocrystals can alter the physicochemical properties of the active pharmaceutical
      ingredient to improve solubility, dissolution rate, particle properties and
      stability. This work presents a process analytical technology (PAT) approach to
      monitor on-line the cocrystallization of furosemide and adenine by solvent
      evaporation using near infrared spectroscopy (NIRS). Furosemide and adenine were
      added to a small volume of methanol in a beaker and stirred on an orbital
      stirring table during 8h at room temperature. The on-line monitoring was
      performed with a FT-NIR spectrometer fitted with a reflectance fiber optic probe.
      Monitoring was performed with the probe tip placed 1cm above the
      cocrystallization medium to avoid interference with the cocrystallization
      process. Cocrystals were vacuum dried to remove residual solvent and
      characterized off-line by NIRS, MIRS, DSC and XRPD. Results demonstrate that it
      was possible to follow the main cocrystallization events on-line. 

PMID- 24907599
TI  - Establishment of powder dustiness evaluation method by dustmeter with small
      amount of pharmaceutical ingredients.
AB  - The ratio of high potent materials in the new chemical entities has recently
      increased in the pharmaceutical industry. Generally, most of them are highly
      hazardous, but there is little toxicity information about the active
      pharmaceutical ingredients in the early development period. Even if their
      handling amount is quite small, the dustiness of high potent powder generated in
      the manufacturing process has an important impact on worker health; thus, it is
      important to understand the powder dustiness. The purpose of this study was to
      establish a method to evaluate the powder dustiness by the consumption of small
      amount of samples. The optimized measurement conditions for a commercially
      available dustmeter were confirmed using lactose monohydrate and naproxen sodium.
      The optimized test conditions were determined: the dustmeter mode, the flow rate,
      the drum rotation speed, the total measurement time, and sample loaded weight
      were type I mode, 4 L/min, 10 rpm, 1 min and 1-10 g , respectively. The setup
      conditions of the dustmeter are considerably valuable to pharmaceutical
      industries, especially, at the early development stage and especially for
      expensive materials, because the amount of air-borne dust can be evaluated with
      accuracy by the consumption of small amount of samples.

PMID- 24907601
TI  - Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal
      pathway after ischemic stroke in rats.
AB  - Physical exercise could play a neuroprotective role in both human and animals.
      However, the involved signal pathways underlying the neuroprotective effect are
      still not well established. This study was to investigate the possible signal
      pathways involved in the neuroprotection of pre-ischemic treadmill training after
      ischemic stroke. Seventy-two SD rats were randomly assigned into three groups
      (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group
      and MCAO with exercise group. Following three weeks of treadmill training
      exercise, ischemic stroke was induced by occluding the middle cerebral artery
      (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after
      MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit
      scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema
      (n=6). Six rats in each group were sacrificed to measure the expression level of
      glutamate transporter-1 (GLT-1), protein kinase C-alpha (PKC-alpha), Akt, and
      phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67
      h) after occlusion, six rats in each group were decapitated to detect the mRNA
      expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D
      aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre
      ischemic treadmill training exercise reduced brain infarct volume, cerebral edema
      and neurological deficits, also decreased the over expression of PKC-alpha and
      increased the expression level of GLT-1, Akt and PI3K after ischemic stroke
      (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre
      ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated
      brain damage after ischemic stroke, which might be involved in two signal
      pathways: PKC-alpha-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate.

PMID- 24907602
TI  - Up-regulation of matrix metallopeptidase 12 in motor neurons undergoing synaptic
      stripping.
AB  - Axotomy of the rodent facial nerve represents a well-established model of
      synaptic plasticity. Post-traumatic "synaptic stripping" was originally
      discovered in this system. We report upregulation of matrix metalloproteinase
      MMP12 in regenerating motor neurons of the mouse and rat facial nucleus. Matrix
      metalloproteinases (matrix metallopeptidases, MMPs) are zinc-binding proteases
      capable of degrading components of the extracellular matrix and of regulating
      extracellular signaling networks including within synapses. MMP12 protein
      expression in facial motor neurons was enhanced following axotomy and peaked at
      day 3 after the operation. The peak of neuronal MMP12 expression preceded the
      peak of experimentally induced synaptic plasticity. At the same time, MMP12
      redistributed intracellularly and became predominantly localized beneath the
      neuronal somatic cytoplasmic membrane. Both findings point to a role of MMP12 in
      the neuronal initiation of the synaptic stripping process. MMP12 is the first
      candidate molecule for such a trigger function and has potential as a therapeutic
      target. Moreover, since statins have been shown to increase the expression of
      MMP12, interference with synaptic stability may represent one mechanism by which
      these widely used drugs exert their side effects on higher CNS functions. 

PMID- 24907603
TI  - Evolutionary morphology of the male reproductive system, spermatozoa and seminal
      fluid of spiders (Araneae, Arachnida)--current knowledge and future directions.
AB  - The male reproductive system and spermatozoa of spiders are known for their high
      structural diversity. Spider spermatozoa are flagellate and males transfer them
      to females in a coiled and encapsulated state using their modified pedipalps.
      Here, we provide a detailed overview of the present state of knowledge of the
      primary male reproductive system, sperm morphology and the structural diversity
      of seminal fluids with a focus on functional and evolutionary implications.
      Secondly, we conceptualized characters for the male genital system,
      spermiogenesis and spermatozoa for the first time based on published and new
      data. In total, we scored 40 characters for 129 species from 56 families
      representing all main spider clades. We obtained synapomorphies for several taxa
      including Opisthothelae, Araneomorphae, Dysderoidea, Scytodoidea, Telemidae,
      Linyphioidea, Mimetidae, Synotaxidae and the Divided Cribellum Clade.
      Furthermore, we recovered synspermia as a synapomorphy for ecribellate Haplogynae
      and thus propose Synspermiata as new name for this clade. We hope that these data
      will not only contribute to future phylogenetic studies but will also stimulate
      much needed evolutionary studies of reproductive systems in spiders. 

PMID- 24907600
TI  - Secretory phospholipase A2 enzymes as pharmacological targets for treatment of
      disease.
AB  - Phospholipase A2 (PLA2) cleave phospholipids preferentially at the sn-2 position,
      liberating free fatty acids and lysophospholipids. They are classified into six
      main groups based on size, location, function, substrate specificity and calcium
      requirement. These classes include secretory PLA2 (sPLA2), cytosolic (cPLA2),
      Ca(2+)-independent (iPLA2), platelet activating factor acetylhydrolases (PAF-AH),
      lysosomal PLA2 (LyPLA2) and adipose specific PLA2 (AdPLA2). It is hypothesized
      that PLA2 can serve as pharmacological targets for the therapeutic treatment of
      several diseases, including cardiovascular diseases, atherosclerosis, immune
      disorders and cancer. Special emphasis has been placed on inhibitors of sPLA2
      isoforms as pharmacological moieties, mostly due to the fact that these enzymes
      are activated during inflammatory events and because their expression is
      increased in several diseases. This review focuses on understanding how sPLA2
      isoform expression is altered during disease progression and the possible
      therapeutic interventions to specifically target sPLA2 isoforms, including new
      approaches using nano-particulate-based strategies. 

PMID- 24907604
TI  - Controlled delivery of inhaled therapeutic agents.
AB  - There is increasing interest in the delivery of drugs to the lungs to treat a
      variety of diseases. The spatial and temporal influence of deposition and
      clearance mechanisms on the fate of inhaled materials are important factors in
      the control of delivery of therapeutic agents to the lungs. Balancing anatomical
      and physiological considerations with pharmaceutical properties dictates the
      therapeutic potential of any pharmacological and immunological strategy. A brief
      introduction of aerosol properties and inhaler technology is followed by
      considerations of in vitro and in vivo disposition in the context of controlled
      drug release for achieving anatomical, physiological and therapeutic targeting.
      Comprehensive assessment of drug delivery to, and disposition from, the lungs is
      required if controlled and targeted strategies are to be successful. 

PMID- 24907605
TI  - On the history of a reoccurring concept: phosphorus scarcity.
AB  - Despite evidence against imminent global phosphate rock depletion, phosphorus (P)
      scarcity scenarios and the subsequent consequences for global food security
      continue to be a matter of controversy. We provide a historicizing account to
      evaluate the degree and relevance of past human experiences with P scarcity.
      Using more than 80 literature sources, we trace the origin of the P scarcity
      concept and the first accounts of concerns; we report on three cases of scarcity
      discourse in the U.S. and revisit the concept of future resources. In addition,
      we present past evaluations of phosphate rock reserves and lifetime estimates for
      the world, the U.S., Morocco, and the Western Sahara, as well as past attempts to
      model phosphorus supply or collect information on phosphate rock. Our results
      show that current concerns have a long legacy and knowledge base to draw from and
      that promulgating the notion of depletion is inconsistent with past findings. We
      find that past depletion concerns were refuted by means of new resource
      appraisals, indicating that the supply was substantially larger than previously
      thought. Moreover, recommendations for national P conservation policies and other
      practices seem to have found little implementation. We demonstrate the merit of
      historic literacy for social learning and the weakness of the current P
      sustainability debate because it does not include this past knowledge. 

PMID- 24907606
TI  - Contamination profiles of antibiotic resistance genes in the sediments at a
      catchment scale.
AB  - The aim of this study was to investigate the contamination profiles of
      tetracycline, sulfonamide, and macrolide resistance genes, as well as integrons
      in sediments of Dongjiang River basin of South China by real time quantitative
      polymerase chain reaction. sul2 was the most abundant resistance gene, with the
      average concentration of 6.97*10(8) copies/g and 1.00*10(8) copies/g in the dry
      and wet seasons, respectively, followed by ermF, sul3, sul1, intI1, tetA, ermB,
      tetX, tetM, tetQ, tetO, tetW, tetS, ermC, and tetB. The abundance of intI2 gene
      was the lowest in the sediment samples. Significant correlations existed between
      the ARGs and sediment properties as well as metals (Cu and Zn) and corresponding
      antibiotic classes, suggesting that the contamination of ARGs is related to
      chemical pollution of the sediments in the river basin. Principal component
      analysis showed distinct groupings of the sampling sites, reflecting that human
      activities are the key player in the dissemination of ARGs in the catchment
      environment.

PMID- 24907607
TI  - Agro-forest landscape and the 'fringe' city: a multivariate assessment of land
      use changes in a sprawling region and implications for planning.
AB  - The present study evaluates the impact of urban expansion on landscape
      transformations in Rome's metropolitan area (1500 km(2)) during the last sixty
      years. Landscape composition, structure and dynamics were assessed for 1949 and
      2008 by analyzing the distribution of 26 metrics for nine land-use classes.
      Changes in landscape structure are analysed by way of a multivariate statistical
      approach providing a summary measure of rapidity-to-change for each metric and
      class. Land fragmentation increased during the study period due to urban
      expansion. Poorly protected or medium-low value added classes (vineyards, arable
      land, olive groves and pastures) experienced fragmentation processes compared
      with protected or high-value added classes (e.g. forests, olive groves) showing
      larger 'core' areas and lower fragmentation. The relationship observed between
      class area and mean patch size indicates increased fragmentation for all uses of
      land (both expanding and declining) except for urban areas and forests. Reducing
      the impact of urban expansion for specific land-use classes is an effective
      planning strategy to contrast the simplification of Mediterranean landscape in
      peri-urban areas.

PMID- 24907608
TI  - Estimation of amphetamine and methamphetamine uses in Beijing through sewage
      based analysis.
AB  - Sewage epidemiology has been proven as an effective approach to estimate the use
      of illicit drugs by a population. In this study, sewage analysis was applied to
      examine the patterns of amphetamine (AMP) and methamphetamine (METH) uses in the
      urban area of Beijing. Influent and effluent samples were collected from all the
      thirteen sewage treatment plants (STPs) in the urban area during two sampling
      campaigns. METH concentrations in influents were found to range from several tens
      to several hundred ng.L(-1), whereas AMP concentrations ranged from several to
      several tens ng.L(-1). The concentration ratios between AMP and METH in influents
      at most STPs were close to the rate of AMP excretion following METH ingestion,
      indicating that AMP in sewage in Beijing was predominately from the metabolism of
      METH. Much higher METH loads were observed in the center part of the urban area
      in Beijing, indicating a strong correlation between METH use and economic level
      and entertainment activities. Seasonal variation in METH loads was significant,
      with greater use in summer than in winter. Significant difference in METH loads
      between weekdays and weekend days were observed in winter but not in summer. No
      clear trend in diurnal variation of METH use was observed. Nearly complete
      removal of METH occurred at the STPS in Beijing. Apparent removal rates of AMP
      were lower than those of METH, likely due to degradation of METH into AMP during
      the wastewater treatment processes. In summary, this study represents the first
      application of sewage epidemiology to the entire urban population of a
      metropolitan in mainland China and provided an overview of METH and AMP uses in
      the city.

PMID- 24907609
TI  - The legal framework to manage chemical pollution in India and the lesson from the
      Persistent Organic Pollutants (POPs).
AB  - India's rapid agro-economic growth has resulted into many environmental issues,
      especially related to chemical pollution. Environmental management and control of
      toxic chemicals have gained significant attention from policy makers,
      researchers, and enterprises in India. The present study reviews the policy and
      legal and non-regulatory schemes set in place in this country during the last
      decades to manage chemical risk and compares them with those in developed
      nations. India has a large and fragmented body of regulation to control and
      manage chemical pollution which appears to be ineffective in protecting
      environment and human health. The example of POPs contamination in India is
      proposed to support such a theory. Overlapping of jurisdictions and
      retrospectively approached environmental policy and risk management currently
      adopted in India are out of date and excluding Indian economy from the process of
      building and participating into new, environmentally-sustainable market spaces
      for chemical products. To address these issues, the introduction of a new
      integrated and scientifically-informed regulation and management scheme is
      recommended. Such scheme should acknowledge the principle of risk management
      rather than the current one based on risk acceptance. To this end, India should
      take advantage of the experience of recently introduced chemical management
      regulation in some developed nations. 

PMID- 24907610
TI  - Sources of indoor and outdoor PM2.5 concentrations in primary schools.
AB  - Children spend a third of their day in the classroom, where air pollution levels
      may differ substantially from those outdoors due to specific indoor sources. Air
      pollution exposure assessments based on atmospheric particle mass measured
      outdoors may therefore have little to do with the daily PM dose received by
      school children. This study aims to investigate outdoor and indoor sources of
      PM2.5 measured at 39 primary schools in Barcelona during 2012. On average 47% of
      indoor PM2.5 measured concentrations was found to be generated indoors due to
      continuous resuspension of soil particles (13%) and a mixed source (34%)
      comprising organic (skin flakes, clothes fibers, possible condensation of VOCs)
      and Ca-rich particles (from chalk and building deterioration). Emissions from
      seven outdoor sources penetrated easily indoors being responsible for the
      remaining 53% of measured PM2.5 indoors. Unpaved playgrounds were found to
      increase mineral contributions in classrooms by 5-6 MUg/m(3) on average with
      respect to schools with paved playgrounds. Weekday traffic contributions varied
      considerably across Barcelona within ranges of 1-14 MUg/m(3) outdoor and 1-10
      MUg/m(3) indoor. Indoors, traffic contributions were significantly higher (more
      than twofold) for classrooms with windows oriented directly to the street, rather
      than to the interior of the block or to playgrounds. This highlights the
      importance of urban planning in order to reduce children's exposure to traffic
      emissions.

PMID- 24907611
TI  - Use of lipid biomarkers for identification of regional sources and dechlorination
      characteristics of polychlorinated biphenyls in the East China Sea.
AB  - Terrestrial organic matter (TOM) indicators could serve as proxies in studying
      the environmental behavior of organic pollutants because they are transported
      into the shelf seas along with the TOM. In this study, comparisons between
      polychlorinated biphenyls (PCBs) and TOM indicators of ?C27+C29+C31n-alkanes, as
      well as branched and isoprenoid tetraether (BIT) index, were performed to examine
      the regional sources of PCBs in the East China Sea. The results indicated that
      sedimentary PCBs in the mud area southwest of the Cheju Island, coastal area
      north of the 29 degrees N, and coastal area south of the 29 degrees N were mainly
      from atmospheric deposition, riverine input of the Yangtze River, and local
      coastal sources via atmospheric deposition, respectively. The broad resemblance
      of the spatial patterns of non-definitive indicators of PCB dechlorination,
      hypoxia, and ?ladderane lipids suggested that deep dechlorination mainly occurred
      at the coastal areas and center shelf southwest of Cheju Island. 

PMID- 24907612
TI  - Assessment of air pollutant sources in the deposit on monuments by multivariate
      analysis.
AB  - A proper recognition of the pollutant sources in atmospheric deposit is a key
      problem for any action aiming at reducing their emission, being this an important
      issue with implications both on human health safeguard and on the cultural
      heritage conservation in urban sites. This work presents the results of a
      statistical approach application for the identification of pollutant sources in
      deposits and damage layers on monuments located in different European sites:
      Santa Maria del Fiore, Florence (Italy), Cologne Cathedral, Cologne (Germany),
      Ancient ramparts, Sale (Morocco), National Museum, Cracow (Poland) and National
      Gallery, Oslo (Norway). For this aim, the surface damage layers on monuments and
      historical buildings of the selected sites were collected and analyzed, in terms
      of ionic and elemental composition, through application of ion chromatography and
      induced coupled plasma-optical emission spectroscopy. The achieved results were
      processed by multivariate analyses such as correlation matrix and principal
      component analysis in order to identify the possible origin of pollutants
      affecting the state of conservation of the monuments. This allowed us to assume
      that in all case studies the traffic emission is the main pollutant source. In
      the case of Ancient ramparts, Sale (Morocco), and National Gallery, Oslo
      (Norway), the surfaces are also under influence of marine aerosols. Moreover,
      concerning the Cologne Cathedral, the strong impact of the pollutants emitted by
      railway station was also revealed. 

PMID- 24907613
TI  - Assessment of personal exposure to particulate air pollution during commuting in
      European cities--recommendations and policy implications.
AB  - Commuting is considered as one of the high-exposure periods among various daily
      activities, especially in high vehicle-density metropolitan areas. There is a
      growing awareness of the need to change our transportation habits by reducing our
      use of cars and shifting instead to active transport, i.e. walking or cycling. A
      review was undertaken using the ISI web of knowledge database with the objective
      to better understand personal exposure during commuting by different modes of
      transport, and to suggest potential strategies to minimise exposure. The air
      pollutants studied include particulate matter, PM black carbon, BC and particle
      number concentration. We focused only in European studies in order to have
      comparable situation in terms of vehicle fleet and policy regulations applied.
      Studies on personal exposure to air pollutants during car commuting are more
      numerous than those dealing with other types of transport, and typically conclude
      by emphasising that travelling by car involves exposure to relatively high
      particulate matter, PM exposure concentrations. Thus, compared to other transport
      methods, travelling by car has been shown to involve exposure both to higher PM
      and BC as compared with cycling. Widespread dependence on private car transport
      has produced a significant daily health threat to the urban commuter. However, a
      forward-looking, integrated transport policy, involving the phased renovation of
      existing public vehicles and the withdrawal of the more polluting private
      vehicles, combined with incentives to use public transport and the encouragement
      of commuter physical exercise, would reduce commuters' exposure. 

PMID- 24907614
TI  - Development of a probabilistic multi-zone multi-source computational model and
      demonstration of its applications in predicting PM concentrations indoors.
AB  - This paper highlights the development and application of the probabilistic model
      (IAPPEM), which predicts PM10 and PM2.5 concentrations in the indoor
      environments. A number of features are detailed and justified through simulated
      comparison, which are shown to be necessary when modelling indoor PM
      concentrations. A one minute resolution predicts up to 20% higher peak
      concentrations compared with a 15 min resolution. A modified PM10 deposition
      method, devised to independently analyse the PM2.5 fraction of PM10, predicts up
      to 56% higher mean concentrations. The application of the model is demonstrated
      by a number of simulations. The total PM contribution, from different indoor
      emission sources, was analysed in terms of both emission strength and duration.
      In addition, PM concentrations were examined by varying the location of the
      emission source. A 24-hour sample profile is simulated based on sample data,
      designed to demonstrate the combined functionality of the model, predicting PM10
      and PM2.5 peak concentrations up to 1107+/-175 and 596+/-102 MUg m(-3)
      respectively, whilst predicting PM10 and PM2.5 mean concentrations up to 259+/-21
      and 166+/-11 MUg m(-3) respectively.

PMID- 24907615
TI  - Comparative evaluation of acute and chronic toxicities of CuO nanoparticles and
      bulk using Daphnia magna and Vibrio fischeri.
AB  - Copper oxide (CuO) has various applications, as highlighted by the incorporation
      of this compound as a biocide of antifouling paints for coating ships and
      offshore oil platforms. The objective of this study was to evaluate and compare
      the aquatic toxicity of CuO nanoparticles (NPs) and microparticles (MPs) through
      acute and chronic toxicity tests with the freshwater microcrustacean Daphnia
      magna and an acute toxicity test with the bioluminescent marine bacteria Vibrio
      fischeri. Acute toxicity results for D. magna in tests with CuO NPs (EC50, 48
      h=22 mg L(-1)) were ten times higher than those for tests with CuO MPs (EC50, 48
      h=223.6 mg L(-1)). In both periods of exposure of V. fischeri, the CuO NPs (EC50,
      15m 248+/-56.39 - equivalent to 12.40%; EC50, 30 m 257.6+/-30.8 mg L(-1) -
      equivalent to 12.88%) were more toxic than the CuO MPs (EC50, 15m 2404.6+/-277.4 
      equivalent to 60.10%; EC50, 30 m 1472.9+/-244.7 mg L(-1) - equivalent to
      36.82%). In chronic toxicity tests, both forms of CuO showed significant effects
      (p<0.05) on the growth and reproduction parameters of the D. magna relative to
      the control. Additionally, morphological changes, such as lack of apical spine
      development and malformed carapaces in D. magna, were observed for organisms
      after the chronic test. The toxicity results demonstrate that CuO NPs have a
      higher level of toxicity than CuO MPs, emphasizing the need for comparative
      toxicological studies to correctly classify these two forms of CuO with identical
      CAS registration numbers.

PMID- 24907616
TI  - PCBs and DDTs in light-vented bulbuls from Guangdong Province, South China:
      levels, geographical pattern and risk assessment.
AB  - Thirty-two light-vented bulbuls (Pycnonotus sinensis) were collected from six
      sampling sites in Guangdong Province, South China to investigate the geographical
      variation on the occurrence of polychlorinated biphenyls (PCBs),
      dichlorodiphenyltrichloroethane and its metabolites (DDTs). Concentrations of
      PCBs and DDTs in the pectoral muscle of light-vented bulbul ranged from 140 to
      73,000 ng/g lipid weight (lw) and 12 to 4600 ng/g lw, respectively. PCB
      concentrations were significantly higher in birds from e-waste site compared to
      other sampling sites (mean, 18,000 vs 290 ng/g lw, p<0.0001), implying that PCBs
      mainly came from e-waste recycling activities. No significant differences for DDT
      levels were observed among the sampling sites (p=0.092). Differences in PCB
      homologue profiles among the sampling sites were found and can be probably
      ascribed to different local contamination sources. p,p'-DDE (>80%) was the most
      abundant component of DDTs in birds. Compositional pattern of DDTs suggested that
      historical residue was the main source of DDT. The toxic equivalent (TEQ)
      concentrations had significant positive correlations with PCB concentrations,
      indicating that elevated PCB levels may have adverse effects on light-vented
      bulbuls.

PMID- 24907617
TI  - Persistence of Escherichia coli O157 and non-O157 strains in agricultural soils.
AB  - Shiga toxin producing Escherichia coli O157 and non-O157 serogroups are known to
      cause serious diseases in human. However, research on the persistence of E. coli
      non-O157 serogroups in preharvest environment is limited. In the current study,
      we compared the survival behavior of E. coli O157 to that of non-O157 E. coli
      strains in agricultural soils collected from three major fresh produce growing
      areas of California (CA) and Arizona (AZ). Results showed that the nonpathogenic
      E. coli O157:H7 4554 survived longer than the pathogenic E. coli O157:H7 EDL933
      in Imperial Valley CA and Yuma AZ, but not in soils from the Salinas area.
      However, E. coli O157:NM was found to persist significantly longer than E. coli
      O157:H7 EDL933 in all soil tested from the three regions. Furthermore, two non
      O157 (E. coli O26:H21 and E. coli O103:H2) survived significantly longer than E.
      coli O157:H7 EDL933 in all soils tested. Pearson correlation analysis showed that
      survival of the E. coli strains was affected by different environmental factors.
      Our data suggest that survival of E. coli O157 and non-O157 may be strain and
      soil specific, and therefore, care must be taken in data interpretation with
      respect to survival of this pathogen in different soils. 

PMID- 24907618
TI  - Implications of effluent organic matter and its hydrophilic fraction on zinc(II)
      complexation in rivers under strong urban pressure: aromaticity as an inaccurate
      indicator of DOM-metal binding.
AB  - The zinc binding characteristics of dissolved organic matter (DOM) fractions from
      the Seine River Basin were studied after being separated and extracted according
      to their polarity: hydrophobic, transphilic, and hydrophilic. The applied
      experimental methodology was based on a determination of labile zinc species by
      means of differential pulse anodic stripping voltammetry (DPASV) at increasing
      concentrations of total zinc on a logarithmic scale and at fixed levels of: pH,
      ionic strength, and temperature. Fitting the DOM fractions with two discrete
      classes of ligands successfully allowed determining the conditional zinc binding
      constants (Ki) as well as total ligand density (LiT). The binding constants
      obtained for each DOM fraction were then compared and discussed with respect to
      the hydrophobic/hydrophilic nature and sample origin. Results highlighted a
      strong complexation of zinc to the effluent organic matter and especially the
      most hydrophilic fraction, which also displayed a very low specific UV
      absorbance. Although the biotic ligand model takes into account the quality of
      DOM through UV absorbance in the predictions of metal bioavailability and
      toxicity, this correction is not efficient for urban waters. 

PMID- 24907619
TI  - Temperature, hospital admissions and emergency room visits in Lhasa, Tibet: a
      time-series analysis.
AB  - BACKGROUND: Tibet of China, with an average altitude of over 4000 m, has
      experienced noticeable changes in its climate over the last 50 years. The
      association between temperature and morbidity (most commonly represented by
      hospital admissions) has been documented mainly in developed countries. Little is
      known about patterns in China; nor have the health effects of temperature
      variations been closely studied in highland areas, worldwide. OBJECTIVE: We
      investigated the temperature-morbidity association in Lhasa, the capital city of
      Tibet, using sex- and age-specific hospitalizations, excluding those due to
      external causes. METHODS: A distributed lag non-linear model (DLNM) was applied
      to assess the nonlinear and delayed effects of temperature on morbidity
      (including total emergency room visits, total and cause-specific hospital
      admissions, sex- and age-specific non-external admissions). RESULTS: High
      temperatures are associated with increases in morbidity, to a greater extent than
      low temperatures. Lag effects of high and low temperatures were cause-specific.
      The relative risks (RR) of high temperature for total emergency room visits and
      non-external hospitalizations were 1.162 (95% CI: 1.002-1.349) and 1.161 (95% CI:
      1.007-1.339) respectively, for lag 0-14 days. The strongest cumulative effect of
      heat for lag 0-27 days was on admissions for infectious diseases (RR: 2.067, 95%
      CI: 1.026-4.027). Acute heat effects at lag 0 were related with increases of
      renal (RR: 1.478, 95% CI: 1.005-2.174) and respiratory diseases (RR: 1.119, 95%
      CI: 1.010-1.240), whereas immediate cold effects increased admission for
      digestive diseases (RR: 1.132, 95% CI: 1.002-1.282). Those >=65 years of age and
      males were more vulnerable to high temperatures. CONCLUSION: We provide a first
      look at the temperature-morbidity relationship in Tibet. Exposure to both hot and
      cold temperatures resulted in increased admissions to hospital, but the immediate
      causes varied. We suggest that initiatives should be taken to reduce the adverse
      effects of temperature extremes in Tibet.

PMID- 24907620
TI  - The Pb isotopic record of historical to modern human lead exposure.
AB  - Human teeth and bones incorporate trace amounts of lead (Pb) from the local
      environment during growth and remodeling. Anthropogenic activities have caused
      changes in the natural Pb isotopic background since historical times and this is
      reflected in the Pb isotopes of historical European teeth. Lead mining and use
      increased exponentially during the last century and the isotopic compositions of
      modern human teeth reflect the modern anthropogenic Pb. USA teeth show the most
      radiogenic Pb and Australian teeth show the least radiogenic Pb, a result of
      different Pb ores used in the two regions. During the last century the Australian
      Pb was exported to Europe, Asia, South America, and Africa, resulting in swamping
      of the local environmental Pb signal by the imported Pb. As a result, the modern
      human teeth in Europe show a significant drop to lower isotopic values compared
      with historical times. Similarly, modern human teeth in other regions of the
      world show similar Pb isotopic ratios to modern European teeth reflecting the Pb
      imports. The specific pattern of human Pb exposure allows us to use the Pb
      isotopic signal recorded in the skeleton as a geo-referencing tool. As historical
      European teeth show a distinct Pb signal, we can identify early European skeletal
      remains in the New World and likely elsewhere. In modern forensic investigations
      we can discriminate to some extent Eastern Europeans from Western and Northern
      Europeans. Australians can be identified to some extent in any region in the
      world, although there is some overlap with Western European individuals. Lead
      isotopes can be used to easily identify foreigners in the USA, as modern USA
      teeth are distinct from any other region of the world. By analogy, USA
      individuals can be identified virtually in any other region of the world. 

PMID- 24907621
TI  - The influence of experimental anterior knee pain during running on
      electromyography and articular cartilage metabolism.
AB  - OBJECTIVE: To determine whether anterior knee pain (AKP), during running, acutely
      affects lower-extremity electromyography (EMG) and articular cartilage
      metabolism. METHODS: A within-subjects design was used. Each of 12 able-bodied
      subjects ran on a treadmill for 30 min for three different sessions: control (no
      infusion), sham (0.9% NaCl infusion into the involved-leg infrapatellar fat pad),
      and pain (5.0% NaCl infusion into the involved-leg infrapatellar fat pad).
      Bilateral surface EMG was monitored for the vastus medialis (VM), vastus
      lateralis (VL), and gastrocnemius (GA). Serum cartilage oligomeric matrix protein
      (COMP) concentration was determined before, after, and 60 min after the run. A
      functional analysis approach was used to compare EMG amplitude, across the entire
      stance phase, between sessions and legs. Mixed-model analysis of covariance was
      used to compare serum COMP concentration between sessions, across time. RESULTS:
      Relative to the uninvolved leg, greater involved-leg VL and GA EMG amplitude
      existed during midstance for the sham and control sessions (P < 0.01). During the
      painful session, however, involved-leg VM, VL, and GA EMG amplitude was 5-10%
      less than for the uninvolved leg. COMP concentration immediately post-run was 14%
      and 21% greater than pre-run (P = 0.01) and 60 min post-run concentrations (P <
      0.01), respectively. Session, however, did not significantly influence COMP.
      CONCLUSION: During a 30-min run, AKP acutely alters midstance VM, VL, and GA EMG
      amplitude. AKP during a 30-min run does not, however, acutely influence articular
      cartilage metabolism.

PMID- 24907622
TI  - Melatonin does not modify the concentration of different metals in AbetaPP
      transgenic mice.
AB  - Metals such as aluminum, iron, copper, and zinc have been implicated in the
      etiology of certain neurodegenerative disorders. On the other hand, it is well
      known that citric acid enhances Al absorption through the diet, while melatonin
      may bind such metals and decrease ROS production. In this study, we determined
      the concentrations of Al, Cu, Zn, Fe, and Mn in various tissues of Tg2576 Al
      treated mice. Female mice and wild type littermates were exposed to 1mg Al/g plus
      3.2% of citric acid and melatonin 10mg/kg/day for 15months. At 18months of age,
      metal concentrations were measured in bone, liver, kidney and spleen, as well as
      in three brain regions. In the citric plus Al group, Al levels were higher in
      hippocampus than in cortex and cerebellum, while Al concentration in bone was
      higher than those in kidney, liver and spleen, The current results show that
      exposure to Al plus citric acid did not produce relevant changes in metal levels
      related with genotype. Moreover, co-administration of melatonin with Al did not
      modify significantly metal concentrations in tissues. The present results do not
      support that melatonin can diminish Al or Fe concentrations in various tissues. 

PMID- 24907623
TI  - Combined subchronic toxicity of dichlorvos with malathion or pirimicarb in mice
      liver and serum: a metabonomic study.
AB  - Organophosphorus (OP) and carbamate (CM) pesticides are widely used in
      agriculture. These pesticides are highly toxic to humans and their residues in
      food pose potential threat to human health. In this study, we investigated the
      effect of subchronic low-level exposure of OPs (dichlorvos, DDVP; malathion,
      MAL), CM pirimicarb (PI), or their mixtures (DDVP+MAL, DDVP+PI) on mice liver.
      Metabonomic analysis based on (1)H nuclear magnetic resonance spectroscopy was
      carried out in combination with biochemical assays. Serum metabonomic analysis
      showed that levels of trimethylamine-N-oxide, lactate, acetone, very low- and low
      density lipoprotein and 3-hydroxybutyrate changed after exposure to the
      pesticides. In the liver extracts, lactate, glucose, choline, glutathione,
      alanine, glutamine and isoleucine levels changed after the treatment by
      pesticides. Our results indicated that exposure to low dose DDVP, MAL and PI,
      either alone or in combination lead to alteration of liver glucose, fat and
      protein metabolism, energy metabolism and oxidative balance. This study also
      showed that metabonomics is of potential use in food toxicity study. 

PMID- 24907624
TI  - Taurine ameliorates neuropathy via regulating NF-kappaB and Nrf2/HO-1 signaling
      cascades in diabetic rats.
AB  - Diabetic neuropathy is one of common complications of diabetes mellitus.
      Hyperglycemia induced oxidative stress involves in the development of diabetic
      neuropathy, which could be reversed by supplementation of taurine, an endogenous
      antioxidant. This experiment was conducted to evaluate alterations in the
      expressions of transcription factors [nuclear factor kappa B (NF-kappaB), nuclear
      factor-E2-related factor-2 (Nrf2), and heme oxygenase 1 (HO-1)] and glucose
      transporters and glucose metabolism in the brain of diabetic rats. In a 2*2
      factorially arranged groups, taurine (2%) or water was administered per orally to
      healthy and streptozotocin (STZ)-induced diabetic rats (n=10 per group) for 8
      weeks. Diabetes was associated with weight loss, hyperglycemia, and oxidative
      stress as reflected by increased serum malondialdehyde (MDA) concentrations.
      Diabetic rat brains had increased the NF-kappaB expression and decreased the
      Nrf2, HO-1, GLUT1,3 expressions as compared to healthy rat brains. Supplemental
      taurine did not alter body weight and blood glucose concentration, but partially
      reduced serum MDA concentration in the diabetic rats. Taurine also partially
      alleviated neuroinflammation as reflected by suppressed the NF-kappaB expression
      and enhanced the Nrf2, HO-1, GLUT1,3 expressions in the diabetic rats. In
      conclusion, taurine reduces the severity of oxidative stress through activating
      antioxidative defense signaling pathway in diabetic rat brain.

PMID- 24907625
TI  - Bendamustine combined with donor lymphocytes infusion in Hodgkin's lymphoma
      relapsing after allogeneic hematopoietic stem cell transplantation.
AB  - The management of Hodgkin's lymphoma (HL) recurring after allogeneic stem cell
      transplantation is challenging. We retrospectively describe 18 adults treated
      with bendamustine followed by escalated donor lymphocyte infusion. Hematological
      toxicity was manageable (39% grade III to IV neutropenia and 28% grade III to IV
      thrombocytopenia). The overall response rate was 55%, with 3 complete and 7
      partial responses. Median overall and progression-free survival were 11 (range, 1
      to 52) and 6 (range, 1 to 28) months, respectively. One-year overall survival of
      responders (complete or partial) was 70% (95% confidence interval, 42% to 98%),
      although it was only 16% for nonresponders (n = 8). Our data show that
      bendamustine followed by donor lymphocyte infusion is feasible and can be
      efficacious as salvage treatment in HL relapsing after an allograft. 

PMID- 24907626
TI  - Comparison of chimerism and minimal residual disease monitoring for relapse
      prediction after allogeneic stem cell transplantation for adult acute
      lymphoblastic leukemia.
AB  - Little data are available on the relative merits of chimerism and minimal
      residual disease (MRD) monitoring for relapse prediction after allogeneic
      hematopoietic stem cell transplantation (HCT). We performed a retrospective
      analysis of serial chimerism assessments in 101 adult HCT recipients with acute
      lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22
      patients. All patients had received myeloablative conditioning. The cumulative
      incidence of relapse was significantly higher in the patients with increasing
      mixed chimerism (in-MC) compared with those with complete chimerism, low-level
      MC, and decreasing MC, but the sensitivity of in-MC detection with regard to
      relapse prediction was only modest. In contrast, MRD assessment was highly
      sensitive and specific. Patients with MRD positivity after HCT had the highest
      incidence of relapse among all prognostic groups analyzed. The median time from
      MRD positivity to relapse was longer than the median time from detection of in
      MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD
      assessment is a powerful prognostic tool that should be included in the routine
      post-transplantation monitoring of patients with ALL, but chimerism analysis may
      provide additional information in some cases. Integration of these tools and
      clinical judgment should allow optimal decision making with regard to post
      transplantation therapeutic interventions. 

PMID- 24907627
TI  - Donor chimerism early after reduced-intensity conditioning hematopoietic stem
      cell transplantation predicts relapse and survival.
AB  - The impact of early donor cell chimerism on outcomes of T cell-replete reduced
      intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is
      ill defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism
      after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding
      patients who died or relapsed before D30. When available, donor T cell chimerism
      was also assessed. The primary outcome was overall survival (OS). Secondary
      outcomes included progression-free survival (PFS), relapse, and nonrelapse
      mortality (NRM). We evaluated 688 patients with hematologic malignancies (48%
      myeloid and 52% lymphoid) and a median age of 57 years (range, 18 to 74)
      undergoing RIC HSCT with T cell-replete donor grafts (97% peripheral blood; 92%
      HLA-matched), with a median follow-up of 58.2 months (range, 12.6 to 120.7). In
      multivariable analysis, total donor cell and T cell chimerism at D30 and D100
      each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most
      predictive. D100 total donor cell chimerism <90% was associated with increased
      relapse (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.83 to 3.51; P <
      .0001), impaired PFS (HR, 2.01; 95% CI, 1.53 to 2.65; P < .0001), and worse OS
      (HR, 1.50; 95% CI, 1.11 to 2.04, P = .009), but not with NRM (HR, .76; 95% CI,
      .44 to 2.27; P = .33). There was no additional utility of incorporating sustained
      D30 to D100 total donor cell chimerism or T cell chimerism. Low donor chimerism
      early after RIC HSCT is an independent risk factor for relapse and impaired
      survival. Donor chimerism assessment early after RIC HSCT can prognosticate for
      long-term outcomes and help identify high-risk patient cohorts who may benefit
      from additional therapeutic interventions. 

PMID- 24907628
TI  - Effects of metronidazole on proopiomelanocortin a gene expression in zebrafish.
AB  - The Metronidazole (MTZ), a widely used antibiotic for treating variations of
      infections, recently is applied in a powerful tool for specifically ablating
      cells or tissues when combined with E. coli nitroreductase (NTR). Although some
      undesired biological effects on eukaryote cells have been reported previously,
      the toxicological mechanism of MTZ has not been uncovered yet. In current study,
      we found that MTZ can induce proopiomelanocortin a (pomca) expression in
      zebrafish larvae. The effect of MTZ is in stage-sensitive and dose-dependent
      manner. A pro-proliferation activity of MTZ on pomca-expressing cells in the
      pituitary at larval stage was also observed. Furthermore, up-regulated levels of
      prolactin (prl) and glycoprotein hormone subunit alpha (gsualpha) were also
      observed after the MTZ treatment. Therefore, utilizing our zebrafish as in vivo
      model, we concluded that MTZ can interfere the endocrine signals in the pituitary
      hormone genes expression. Our current results raised the cautions to the
      intensively application of MTZ in clinical practices and biomedical researches. 

PMID- 24907629
TI  - Thyroid hormone and retinoid X receptor function and expression during sea
      lamprey (Petromyzon marinus) metamorphosis.
AB  - Sea lampreys (Petromyzon marinus) are members of the ancient class Agnatha and
      undergo a metamorphosis that transforms blind, sedentary, filter-feeding larvae
      into free-swimming, parasitic juveniles. Thyroid hormones (THs) appear to be
      important for lamprey metamorphosis, however, serum TH concentrations are
      elevated in the larval phase, decline rapidly during early metamorphosis and
      remain low until metamorphosis is complete; these TH fluctuations are contrary to
      those of other metamorphosing vertebrates. Moreover, thyroid hormone synthesis
      inhibitors (goitrogens) induce precocious metamorphosis and exogenous TH
      treatments disrupt natural metamorphosis in P. marinus. Given that THs exert
      their effects by binding to TH nuclear receptors (TRs) that often act as
      heterodimers with retinoid X receptors (RXRs), we cloned and characterized these
      receptors from P. marinus and examined their expression during metamorphosis. Two
      TRs (PmTR1 and PmTR2) and three RXRs (PmRXRs) were isolated from P. marinus cDNA.
      Phylogenetic analyses group the PmTRs together on a branch prior to the
      gnathostome TRalpha/beta split. The three RXRs also group together, but our data
      indicated that these transcripts are most likely either allelic variants of the
      same gene locus, or the products of a lamprey-specific duplication event.
      Importantly, these P. marinus receptors more closely resemble vertebrate as
      opposed to invertebrate chordate receptors. Functional analysis revealed that
      PmTR1 and PmTR2 can activate transcription of TH-responsive genes when treated
      with nanomolar concentrations of TH and they have distinct pharmacological
      profiles reminiscent of vertebrate TRbeta and TRalpha, respectively. Also similar
      to other metamorphosing vertebrates, expression patterns of the PmTRs during
      lamprey metamorphosis suggest that PmTR1 has a dynamic, tissue-specific
      expression pattern that correlates with tissue morphogenesis and biochemical
      changes and PmTR2 has a more uniform expression pattern. This TR expression data
      suggests that THs, either directly or via a metabolite, may function to
      positively modulate changes at the tissue or organ levels during lamprey
      metamorphosis. Collectively the results presented herein support the hypothesis
      that THs have a dual functional role in the lamprey life cycle whereby high
      levels promote larval feeding, growth and lipogenesis and low levels promote
      metamorphosis. 

PMID- 24907630
TI  - Do displacement activities help preschool children to inhibit a forbidden action?
AB  - Displacement activities are commonly recognized as behavioral patterns, mostly
      including self-directed actions (e.g., scratching, self-touching), that often
      occur in situations involving conflicting motivational tendencies. In ethology,
      several researchers have suggested that displacement activities could facilitate
      individuals in dealing with the stress experienced in a frustrating context. In
      child developmental research, some authors have assessed whether distraction
      strategies could help children to inhibit a dominant response during delay of
      gratification tasks. However, little is known about the displacement activities
      that young children may produce in such situations. This study was aimed at
      investigating whether displacement activities had an effect on preschool
      children's ability to postpone an immediate gratification (i.e., interacting with
      an attractive toy, a musical box), thereby functioning as regulators of their
      emotional state. To this end, we administered 143 2- to 4-year-olds with a delay
      maintenance task and related their performance with displacement activities they
      produced during the task and with actions with an external object. Children's
      latency to touch the musical box was positively related to their rate of
      displacement activities. However, the rate of displacement activities increased
      progressively as long as the children were able to inhibit the interaction with
      the musical box. In addition, the rate of displacement activities during the
      first 1 min of test did not predict the ability of children to inhibit the
      interaction with the box. These results suggest that displacement activities
      represented a functionless by-product of motivational conflict rather than a
      strategy that children used to inhibit their response to an attractive stimulus.

PMID- 24907631
TI  - No childhood development of viewpoint-invariant face recognition: evidence from 8
      year-olds and adults.
AB  - Performance on laboratory face tasks improves across childhood, not reaching
      adult levels until adolescence. Debate surrounds the source of this development,
      with recent reviews suggesting that underlying face processing mechanisms are
      mature early in childhood and that the improvement seen on experimental tasks
      instead results from general cognitive/perceptual development. One face
      processing mechanism that has been argued to develop slowly is the ability to
      encode faces in a view-invariant manner (i.e., allowing recognition across
      changes in viewpoint). However, many previous studies have not controlled for
      general cognitive factors. In the current study, 8-year-olds and adults performed
      a recognition memory task with two study-test viewpoint conditions: same view
      (study front view, test front view) and change view (study front view, test three
      quarter view). To allow quantitative comparison between children and adults,
      performance in the same view condition was matched across the groups by
      increasing the learning set size for adults. Results showed poorer memory in the
      change view condition than in the same view condition for both adults and
      children. Importantly, there was no quantitative difference between children and
      adults in the size of decrement in memory performance resulting from a change in
      viewpoint. This finding adds to growing evidence that face processing mechanisms
      are mature early in childhood. 

PMID- 24907632
TI  - What makes Simon Says so difficult for young children?
AB  - Compared with conceptually similar response inhibition tasks, the game of Simon
      Says is particularly challenging for young children. However, possible reasons
      for this difference have not been systematically investigated. Here we tested the
      relative influence of two dissociable characteristics of the standard Simon Says
      task: receiving both inhibition and activation commands from the same
      experimenter and seeing the experimenter perform the movement along with the
      commands. A sample of 74 children (mean age = 55 months) were randomly assigned
      to complete one of five possible tasks. Four of the five tasks were variations of
      Simon Says involving combinations of one or two experimenters and the presence
      versus absence of the experimenter's movements. The fifth task was Bear-Dragon, a
      commonly used executive function task in which one experimenter employed two
      puppets to give action commands to children. Analyses revealed that children's
      performance was significantly worse on the one-person Simon Says tasks compared
      with the two-person tasks and the Bear-Dragon task. The presence of the
      experimenters' movements alongside their commands did not have a significant
      effect on children's performance. The requirement to respond to one person who is
      changing how different rules apply to similar actions appears to be an important
      determinant of the difficulty of Simon Says for young children. In terms of
      implications, inconsistency in how an adult applies rules to children's actions
      may be a detrimental social influence on the development of cognitive control
      during early childhood.

PMID- 24907633
TI  - Gene expression analysis of pretreatment biopsies predicts the pathological
      response of esophageal squamous cell carcinomas to neo-chemoradiotherapy.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy (neo-CRT) followed by surgery has been
      shown to improve esophageal squamous cell carcinoma (ESCC) patients' survival
      compared with surgery alone. However, the outcomes of CRT are heterogeneous, and
      no clinical or pathological method can currently predict CRT response. In this
      study, we aim to identify mRNA markers useful for ESCC CRT-response prediction.
      PATIENTS AND METHODS: Gene expression analyses were carried out on pretreated
      cancer biopsies from 28 ESCCs who received neo-CRT and surgery. Surgical
      specimens were assessed for pathological response to CRT. The differentially
      expressed genes identified by expression profiling were validated by real-time
      quantitative polymerase chain reaction (qPCR), and a classifying model was built
      from qPCR data using Fisher's linear discriminant analysis. The predictive power
      of this model was further assessed in a second set of 32 ESCCs. RESULTS: The
      profiling of the 28 ESCCs identified 10 differentially expressed genes with more
      than a twofold change between patients with pathological complete response (pCR)
      and less than pCR (<pCR). A prediction model based on the qPCR values of three
      genes was generated, which provided a predictive accuracy of 86% upon leave-one
      out cross-validation. Furthermore, the predictive power of this model was
      validated in another cohort of 32 ESCCs, among which a predictive accuracy of 81%
      was achieved. Importantly, the discriminant score was found to be the only
      independent factor that affected neo-CRT response in both the training (P =
      0.015) and validation (P = 0.017) sets, respectively. CONCLUSION: The expression
      levels of three genes determined by qPCR provide a possible model for ESCC CRT
      prediction, which will facilitate the individualization of ESCC treatment.
      Further prospective validation in larger independent cohorts is necessary to
      fully assess its predictive power.

PMID- 24907634
TI  - Circulating tumour cells as tumour biomarkers in melanoma: detection methods and
      clinical relevance.
AB  - Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in
      the peripheral blood. Their occurrence is considered a prerequisite step for
      establishing distant metastases. Metastatic melanoma was the first malignancy in
      which CTCs were detected and numerous studies have been published on CTC
      detection in melanoma at various stages of disease. In spite of this, there is no
      general consensus as to the clinical utility of CTCs in melanoma, largely due to
      conflicting results from heterogeneous studies and discrepancies in methods of
      detection between studies. In this review, we examine the possible clinical
      significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on
      detection methods and prognostic value of CTC detection. 

PMID- 24907635
TI  - A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with
      gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer.
AB  - BACKGROUND: Tremelimumab (CP-675,206) is a fully human monoclonal antibody
      binding to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) on T cells that
      stimulates the immune system by blocking the CTLA4-negative regulatory signal.
      Combination with standard chemotherapy may strengthen antitumor therapy. This is
      a phase Ib, multisite, open-label, nonrandomized dose escalation trial evaluating
      the safety, tolerability, and maximum tolerated dose (MTD) of tremelimumab
      combined with gemcitabine in patients with metastatic pancreatic cancer. PATIENTS
      AND METHODS: Gemcitabine (1000 mg/m(2) on days 1, 8, and 15 of each 28-day
      cycles) was administrated with escalating doses of i.v. tremelimumab (6, 10, or
      15 mg/kg) on day 1 of each 84-day cycle for a maximum of 4 cycles. The first 18
      patients had an initial 4-week gemcitabine-only lead-in period. Dose-limiting
      toxicities (DLTs) related to tremelimumab were evaluated during the first 6 weeks
      after the first dose of tremelimumab. RESULTS: From June 2008 to August 2011, 34
      patients were enrolled and received at least one dose of tremelimumab. No DLTs
      related to tremelimumab were observed at any dose, even when the maximum dose
      established for tremelimumab (15 mg/kg) was used. Most frequent grade 3/4
      toxicities were asthenia (11.8%) and nausea (8.8%). Only one patient had a
      serious drug-related event (diarrhea with dehydration). The median overall
      survival was 7.4 months (95% confidence interval 5.8-9.4 months). At the end of
      treatment, two patients achieved partial response. Both patients received
      tremelimumab 15-mg/kg group (n = 2/19, 10.5%). CONCLUSION: Tremelimumab plus
      gemcitabine demonstrated a safety and tolerability profile, warranting further
      study in patients with metastatic pancreatic cancer. CLINICALTRIALSGOV ID:
      NCT00556023.

PMID- 24907637
TI  - Trends in mortality from major cancers in the Americas: 1980-2010.
AB  - BACKGROUND: Between the 1970s and 2000 mortality in most of Latin America showed
      favorable trends for some common cancer sites, including stomach and male lung
      cancer. However, major concerns were related to mortality patterns from other
      cancers, particularly in women. We provide an up-to-date picture of patterns and
      trends in cancer mortality in Latin America. METHODS: We analyzed data from the
      World Health Organization mortality database in 2005-2009 for 20 cancer sites in
      11 Latin American countries and, for comparative purposes, in the USA and Canada.
      We computed age-standardized (world population) rates (per 100 000 person-year)
      and provided an overview of trends since 1980 using joinpoint regression models.
      RESULTS: Cancer mortality from some common cancers (including colorectum and
      lung) is still comparatively low in Latin America, and decreasing trends continue
      for other cancer sites (including stomach, uterus, male lung cancers) in several
      countries. However, there were upward trends for colorectal cancer mortality for
      both sexes, and for lung and breast cancer mortality in women from most
      countries. During the last decade, lung cancer mortality in women rose by 1%-3%
      per year in all Latin American countries except Mexico and Costa Rica, whereas
      rises of about 1% were registered for breast cancer in Brazil, Colombia and
      Venezuela. Moreover, high mortality from cancer of the cervix uteri was recorded
      in most countries, with rates over 13/100 000 women in Cuba and Venezuela. In
      men, upward trends were registered for prostate cancer mortality in Brazil and
      Colombia, but also in Cuba, where the rate in 2005-2009 was more than twice that
      of the USA (23.6 versus 10/100 000). CONCLUSIONS: Tobacco control, efficient
      screening programs, early cancer detection and widespread access to treatments
      continue to be a major priority for cancer prevention in most Latin American
      countries.

PMID- 24907636
TI  - Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine
      with booster inoculations to prevent disease recurrence in high-risk breast
      cancer patients.
AB  - BACKGROUND: E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3
      restricted immunogenic peptide derived from the HER2 protein. We have conducted
      phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S
      and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adjuvant
      setting to prevent disease recurrence. All patients have completed 60 months
      follow-up, and here, we report the final analyses. PATIENTS AND METHODS: The
      studies were conducted as dose escalation/schedule optimization trials enrolling
      node-positive and high-risk node-negative patients with tumors expressing any
      degree of HER2 (immunohistochemistry 1-3+). HLA-A2/3+ patients were vaccinated;
      others were followed prospectively as controls. Local and systemic toxicity was
      monitored. Clinical recurrences were documented, and disease-free survival (DFS)
      was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.
      RESULTS: Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the
      vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were
      well matched for clinicopathologic characteristics. Toxicities were minimal. Five
      year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial
      design, 65% of patients received less than the optimal vaccine dose. Five-year
      DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in
      suboptimally dosed patients. A voluntary booster program was initiated, and among
      the 21 patients that were optimally boosted, there was only one recurrence (DFS =
      95.2%). CONCLUSION: The E75 vaccine is safe and appears to have clinical
      efficacy. A phase III trial evaluating the optimal dose and including booster
      inoculations has been initiated. CLINICAL TRIALS: NCT00841399, NCT00584789.

PMID- 24907638
TI  - Noninvasive and painless magnetic stimulation of nerves improved brain motor
      function and mobility in a cerebral palsy case.
AB  - Motor deficits in cerebral palsy disturb functional independence. This study
      tested whether noninvasive and painless repetitive peripheral magnetic
      stimulation could improve motor function in a 7-year-old boy with spastic
      hemiparetic cerebral palsy. Stimulation was applied over different nerves of the
      lower limbs for 5 sessions. We measured the concurrent aftereffects of this
      intervention on ankle motor control, gait (walking velocity, stride length,
      cadence, cycle duration), and function of brain motor pathways. We observed a
      decrease of ankle plantar flexors resistance to stretch, an increase of active
      dorsiflexion range of movement, and improvements of corticospinal control of
      ankle dorsiflexors. Joint mobility changes were still present 15 days after the
      end of stimulation, when all gait parameters were also improved. Resistance to
      stretch was still lower than prestimulation values 45 days after the end of
      stimulation. This case illustrates the sustained effects of repetitive peripheral
      magnetic stimulation on brain plasticity, motor function, and gait. It suggests a
      potential impact for physical rehabilitation in cerebral palsy. 

PMID- 24907639
TI  - Goal management tendencies predict trajectories of adjustment to lower limb
      amputation up to 15 months post rehabilitation discharge.
AB  - OBJECTIVES: To explore patterns of change in positive affect, general adjustment
      to lower-limb amputation, and self-reported disability from rehabilitation
      admission to 15 months postdischarge, and to examine whether goal pursuit and
      goal adjustment tendencies predict either initial status or rates of change in
      these outcomes, controlling for sociodemographic and clinical covariates. DESIGN:
      Prospective cohort study with 4 time points (t1: on admission; t2: 6wk
      postdischarge; t3: 6mo postdischarge; t4: 15mo postdischarge). SETTING: Inpatient
      rehabilitation. PARTICIPANTS: Consecutive sample (N=98) of persons aged >=18
      years with major lower-limb amputation. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Positive affect subscale of the Positive and Negative Affect
      Schedule; general adjustment subscale of the Trinity Amputation and Prosthesis
      Experience Scales-Revised; and World Health Organization Disability Assessment
      Schedule 2.0. RESULTS: Positive affect decreased from t1 to t4 for the overall
      sample, whereas general adjustment increased. Self-reported disability scores
      remained stable over this period. Stronger goal pursuit tendencies were
      associated with greater positive affect at t1, and stronger goal adjustment
      tendencies were associated with more favorable initial scores on each outcome
      examined. With regard to rates of change, stronger goal pursuit tendencies
      buffered against decreases in positive affect and promoted decreases in self
      reported disability over time, whereas stronger goal adjustment tendencies
      enhanced increases in general adjustment to lower-limb amputation. CONCLUSIONS:
      Greater use of goal pursuit and goal adjustment strategies appears to promote
      more favorable adjustment to lower-limb amputation over time across a range of
      important rehabilitation outcomes.

PMID- 24907640
TI  - Effects of Feldenkrais method on chronic neck/scapular pain in people with visual
      impairment: a randomized controlled trial with one-year follow-up.
AB  - OBJECTIVE: To determine whether the Feldenkrais method is an effective
      intervention for chronic neck/scapular pain in patients with visual impairment.
      DESIGN: Randomized controlled trial with an untreated control group. SETTING: Low
      vision center. PARTICIPANTS: Patients (N=61) with visual impairment (mean, 53.3
      y) and nonspecific chronic (mean, 23.8 y) neck/scapular pain. INTERVENTIONS:
      Participants were randomly assigned to the Feldenkrais method group (n=30) or
      untreated control group (n=31). Patients in the treatment group underwent one 2
      hour Feldenkrais method session per week for 12 consecutive weeks. MAIN OUTCOME
      MEASURES: Blind assessment of perceived pain (visual analog scale [VAS]) during
      physical therapist palpation of the left and right occipital, upper trapezius,
      and levator scapulae muscle areas; self-assessed degree of pain on the Visual,
      Musculoskeletal, and Balance Complaints questionnaire; and the Medical Outcomes
      Study 36-Item Short-Form Health Survey bodily pain scale. RESULTS: Patients
      undergoing Feldenkrais method reported significantly less pain than the controls
      according to the VAS and Visual, Musculoskeletal, and Balance Complaints
      questionnaire ratings at posttreatment follow-up and 1-year follow-up. There were
      no significant differences regarding the Medical Outcomes Study 36-Item Short
      Form Health Survey bodily pain scale ratings. CONCLUSIONS: Feldenkrais method is
      an effective intervention for chronic neck/scapular pain in patients with visual
      impairment.

PMID- 24907641
TI  - Abnormal splicing of NEDD4 in myotonic dystrophy type 2: possible link to statin
      adverse reactions.
AB  - Myotonic dystrophy type 2 (DM2) is a multisystemic disorder caused by a (CCTG)n
      repeat expansion in intron 1 of CNBP. Transcription of the repeats causes a toxic
      RNA gain of function involving their accumulation in ribonuclear foci. This leads
      to sequestration of splicing factors and alters pre-mRNA splicing in a range of
      downstream effector genes, which is thought to contribute to the diverse DM2
      clinical features. Hyperlipidemia is frequent in DM2 patients, but the treatment
      is problematic because of an increased risk of statin-induced adverse reactions.
      Hypothesizing that shared pathways lead to the increased risk, we compared the
      skeletal muscle expression profiles of DM2 patients and controls with patients
      with hyperlipidemia on statin therapy. Neural precursor cell expressed,
      developmentally downregulated-4 (NEDD4), an ubiquitin ligase, was one of the
      dysregulated genes identified in DM2 patients and patients with statin-treated
      hyperlipidemia. In DM2 muscle, NEDD4 mRNA was abnormally spliced, leading to
      aberrant NEDD4 proteins. NEDD4 was down-regulated in persons taking statins, and
      simvastatin treatment of C2C12 cells suppressed NEDD4 transcription. Phosphatase
      and tensin homologue (PTEN), an established NEDD4 target, was increased and
      accumulated in highly atrophic DM2 muscle fibers. PTEN ubiquitination was reduced
      in DM2 myofibers, suggesting that the NEDD4-PTEN pathway is dysregulated in DM2
      skeletal muscle. Thus, this pathway may contribute to the increased risk of
      statin-adverse reactions in patients with DM2. 

PMID- 24907643
TI  - Impact of biatrial defragmentation in patients with paroxysmal atrial
      fibrillation: results from a randomized prospective study.
AB  - BACKGROUND: Single procedure success rates of pulmonary vein isolation (PVI) in
      patients with paroxysmal atrial fibrillation (PAF) are still unsatisfactory. In
      patients with persistent atrial fibrillation (AF), ablation of complex
      fractionated atrial electrograms (CFAEs) after PVI results in improved outcomes.
      OBJECTIVE: We aimed to investigate if PAF-patients with intraprocedurally
      sustained AF after PVI might benefit from additional CFAE ablation. METHODS: A
      total of 1134 consecutive patients underwent a first catheter ablation procedure
      of PAF between June 2008 and December 2012. In most patients, AF was either not
      inducible or terminated during PVI. In 68 patients (6%), AF sustained after
      successful PVI. These patients were randomized to either cardioversion (PVI-alone
      group; n = 33) or additional CFAE ablation (PVI+CFAE group; n = 35) and followed
      up every 1-3 months and serial Holter recordings were also obtained. The primary
      end point was the recurrence of AF/atrial tachycardia (AT) after a blanking
      period of 3 months. RESULTS: Procedure duration (127 +/- 6 minutes vs 174 +/- 10
      minutes), radiofrequency application time (44 +/- 3 minutes vs 74 +/- 5 minutes),
      and fluoroscopy time (26 +/- 2 minutes vs 41 +/- 3 minutes) were longer in the
      PVI+CFAE group (all P < .001). In 30 of 35 patients (86%) in the PVI+CFAE group,
      ablation terminated AF. There was no significant group difference with respect to
      freedom from AF/AT (22 of 33 [67%] vs 22 of 35 [63%]; P = .66). Subsequently, 10
      of 11 patients in the PVI-alone group (91%) and 11 of 13 patients in PVI+CFAE
      group (85%) underwent repeat ablation (P = 1.00). Overall, 29 of 33 [88%] vs 30
      of 35 [86%] patients (P = 1.00) were free from AF/AT after 1.4 +/- 0.1 vs 1.4 +/-
      0.2 (P = .87) procedures. CONCLUSION: Patients with sustained AF after PVI in a
      PAF cohort are rare. Regarding AF/AT recurrence, these patients did not benefit
      from further CFAE ablation compared to PVI alone, but are exposed to longer
      procedure duration, fluoroscopy time, and radiofrequency application time.

PMID- 24907642
TI  - Novel nuclear localization of fatty acid synthase correlates with prostate cancer
      aggressiveness.
AB  - Fatty acid synthase is up-regulated in a variety of cancers, including prostate
      cancer. Up-regulation of fatty acid synthase not only increases production of
      fatty acids in tumors but also contributes to the transformed phenotype by
      conferring growth and survival advantages. In addition, increased fatty acid
      synthase expression in prostate cancer correlates with poor prognosis, although
      the mechanism(s) by which this occurs are not completely understood. Because
      fatty acid synthase is expressed at low levels in normal cells, it is currently a
      major target for anticancer drug design. Fatty acid synthase is normally found in
      the cytosol; however, we have discovered that it also localizes to the nucleus in
      a subset of prostate cancer cells. Analysis of the fatty acid synthase protein
      sequence indicated the presence of a nuclear localization signal, and subcellular
      fractionation of LNCaP prostate cancer cells, as well as immunofluorescent
      confocal microscopy of patient prostate tumor tissue and LNCaPs confirmed nuclear
      localization of this protein. Finally, immunohistochemical analysis of prostate
      cancer tissue indicated that nuclear localization of fatty acid synthase
      correlates with Gleason grade, implicating a potentially novel role in prostate
      cancer progression. Possible clinical implications include improving the accuracy
      of prostate biopsies in the diagnosis of low- versus intermediate-risk prostate
      cancer and the uncovering of novel metabolic pathways for the therapeutic
      targeting of androgen-independent prostate cancer. 

PMID- 24907644
TI  - Structure function attributes of gold nanoparticle vaccine association: effect of
      particle size and association temperature.
AB  - Many biotherapeutic applications of gold nanoparticles make use of conjugated or
      adsorbed protein moieties. Physical parameters of association such as particle
      size, morphology, surface chemistry and temperature influences the protein
      nanoparticle association and thereby their interaction with the biological
      environment. In present study, effect of size of chitosan reduced gold
      nanoparticles (CsAuNPs) and association temperature on structure and function of
      tetanus toxoid (TT) vaccine has been investigated. CsAuNPs were synthesized in
      the sizes of 20+/-3, 40+/-5 and 80+/-7 nm followed by loading of TT. Binding
      process of CsAuNPs with TT was investigated at their predetermined micro molar
      concentrations. Upon binding of TT onto CsAuNPs, particle surface was
      characterized using X-ray photoelectron spectroscopy. CD spectroscopic evaluation
      of TT bound 20 nm CsAuNPs led to 75% reduction in secondary structure of TT and
      thereby compromised immune function. Binding of TT with 40 and 80 nm sized
      CsAuNPs did not cause significant modifications in secondary structure or
      function of TT. Thermodynamic studies using temperature dependent fluorescence
      spectroscopy revealed an increase in association constants with the temperature.
      Based on thermodynamic data three phases in CsAuNPs and TT association process
      were traced. Samples from these distinct phases were also investigated for
      immunological recognition. Ex-vivo interaction of TT-CsAuNPs with TT positive and
      negative sera followed by relative change in particle size and zeta potential was
      studied. The findings here suggests prominent role of particle size and
      association temperature on adsorbed TT structure and function. Such studies may
      help in engineering functional nanotherapeutics.

PMID- 24907645
TI  - Analytical evidence of heterogeneous lead accumulation in the hypothalamic
      defence area and nucleus tractus solitarius.
AB  - Lead is a potent toxicant associated with adverse cardiovascular effects and
      hypertension in children. Yet, few studies have determined if autonomic
      dysfunction associated with lead exposure involves brain regions which regulate
      autonomic responses. Central autonomic nuclei such as the nucleus tractus
      solitarius (NTS) and hypothalamic defence area (HDA) may be particularly
      sensitive to lead infiltration because they are adjacent to ventricles and areas
      with semi-permeable blood-brain-barriers. To understand if autonomic nuclei are
      sensitive to lead accumulation Wistar rats were exposed to lead from the
      gestational period and lead levels were quantified in brain regions that regulate
      arterial pressure: the NTS and the HDA. Energy dispersive X-ray fluorescence
      (EDXRF) was used to quantify total brain lead levels and revealed no differences
      between exposed and control tissues; measured values were close to the detection
      limit (2MUg/g). Electrothermal atomic absorption spectrometry (ETAAS) was also
      used, which has a greater sensitivity, to quantify lead. There was ~2.1MUg/g lead
      in the NTS and ~3.1MUg/g lead in the HDA of exposed rats, and no lead in the
      control rats. There were greater lead levels in the HDA (~50%) as compared with
      the NTS. Pathology studies revealed more prominent lead granules in the HDA as
      compared with the NTS. Increased microglia and astrocyte activation was also
      noted in the NTS of lead exposed rats as compared with the HDA. Regional
      differences in neuro-inflammatory responses likely contribute to heterogeneous
      lead accumulation, with enhanced clearance of lead in the NTS. Future studies
      will resolve the mechanisms underpinning tissue-specific lead accumulation. 

PMID- 24907646
TI  - Quantification of biliary excretion and sinusoidal excretion of 5(6)-carboxy
      2',7'-dichlorofluorescein (CDF) in cultured hepatocytes isolated from Sprague
      Dawley, Wistar and Mrp2-deficient Wistar (TR(-)) rats.
AB  - Hepatic efflux of drug candidates is an important issue in pre-clinical drug
      development. Here we utilise a method which quantifies and distinguishes efflux
      of drugs at the canalicular and sinusoidal membranes in rat hepatocyte cultures.
      Bi-phasic kinetics of transport of 5(6)-carboxydichlorofluorescein (CDF) at the
      canalicular membrane was demonstrated in Sprague Dawley (SD) and Wistar (W) rat
      hepatocytes. The high affinity component (Km=3.2+/-0.8MUM (SD), 9.0+/-3.1MUM (W))
      was attributed to Mrp2-mediated transport, the low affinity component (Km=192.1+/
      291.5MUM (SD), 69.2+/-36.2MUM (W)) may be attributed to transport involving a
      separate Mrp2 binding site. Data from membranes (Hill coefficient (h)=2.0+/-0.5)
      and vesicles (h=1.6+/-0.2) expressing Mrp2 and from SD (h=1.6+/-0.4) and Wistar
      (h=4.0+/-0.6) hepatocytes suggests transport involves more than one binding site.
      In TR(-) hepatocytes, CDF efflux was predominantly over the sinusoidal membrane
      (Km=100.7+/-36.0MUM), consistent with low abcc2 (Mrp2) expression and
      compensatory increase in abcc3 (Mrp3) expression. This report shows the potential
      of using this in vitro method to model changes in biliary excretion due to
      alterations in transporter expression. 

PMID- 24907647
TI  - 2-Deoxy-d-glucose attenuates sevoflurane-induced neuroinflammation through
      nuclear factor-kappa B pathway in vitro.
AB  - OBJECT: Sevoflurane, one of the most commonly used anesthetics in clinic, induced
      neuroinflammation and caused cognitive impairment. 2-deoxy-d-glucose (2-DG) is a
      synthetic analogue of glucose and is clinically used in medical imaging safely.
      METHODS: We examined the effect of 2-DG on sevoflurane-induced neuroinflammation
      in the mouse primary microglia cells. Mouse microglia cells were treated with
      4.1% sevoflurane for 6h to examine the expression of interleukin (IL)-6 and tumor
      necrosis factor (TNF-alpha) and activation of nuclear factor-kappa B (NF-kappaB).
      Pyrrolidine dithiocarbamate (PDTC) or 2-DG was used 1h before sevoflurane
      treatment. RESULTS: In the present study, we found that sevoflurane increased
      level of IL-6 and TNF-alpha through activating NF-kappaB signaling, and that 2-DG
      reduced sevoflurane-induced increase in IL-6 and TNF-alpha and nuclear NF-kappaB
      in microglia cells. CONCLUSION: Our data suggests that NF-kappaB signaling
      pathway could be a target for sevoflurane-induced neuroinflammation and 2-DG
      might be a potential therapy to prevent or treat sevoflurane-induced
      neuroinflammation.

PMID- 24907649
TI  - Optimization of the elution buffer and concentration method for detecting
      hepatitis E virus in swine liver using a nested reverse transcription-polymerase
      chain reaction and real-time reverse transcription-polymerase chain reaction.
AB  - The aim of this study was to develop an optimal technique for detecting hepatitis
      E virus (HEV) in swine livers. Here, three elution buffers and two concentration
      methods were compared with respect to enhancing recovery of HEV from swine liver
      samples. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and
      nested RT-PCR were performed to detect HEV RNA. When phosphate-buffered saline
      (PBS, pH 7.4) was used to concentrate HEV in swine liver samples using
      ultrafiltration, real-time RT-PCR detected HEV in 6 of the 26 samples. When
      threonine buffer was used to concentrate HEV using polyethylene glycol (PEG)
      precipitation and ultrafiltration, real-time RT-PCR detected HEV in 1 and 3 of
      the 26 samples, respectively. When glycine buffer was used to concentrate HEV
      using ultrafiltration and PEG precipitation, real-time RT-PCR detected HEV in 1
      and 3 samples of the 26 samples, respectively. When nested RT-PCR was used to
      detect HEV, all samples tested negative regardless of the type of elution buffer
      or concentration method used. Therefore, the combination of real-time RT-PCR and
      ultrafiltration with PBS buffer was the most sensitive and reliable method for
      detecting HEV in swine livers. 

PMID- 24907648
TI  - Histone hypoacetylation-activated genes are repressed by acetyl-CoA- and
      chromatin-mediated mechanism.
AB  - Transcriptional activation is typically associated with increased acetylation of
      promoter histones. However, this paradigm does not apply to transcriptional
      activation of all genes. In this study we have characterized a group of genes
      that are repressed by histone acetylation. These histone hypoacetylation
      activated genes (HHAAG) are normally repressed during exponential growth, when
      the cellular level of acetyl-CoA is high and global histone acetylation is also
      high. The HHAAG are induced during diauxic shift, when the levels of acetyl-CoA
      and global histone acetylation decrease. The histone hypoacetylation-induced
      activation of HHAAG is independent of Msn2/Msn4. The repression of HSP12, one of
      the HHAAG, is associated with well-defined nucleosomal structure in the promoter
      region, while histone hypoacetylation-induced activation correlates with
      delocalization of positioned nucleosomes or with reduced nucleosome occupancy.
      Correspondingly, unlike the majority of yeast genes, HHAAG are transcriptionally
      upregulated when expression of histone genes is reduced. Taken together, these
      results suggest a model in which histone acetylation is required for proper
      positioning of promoter nucleosomes and repression of HHAAG. 

PMID- 24907650
TI  - High performance liquid chromatography coupled to electrospray ionization and
      quadrupole time-of-flight-mass spectrometry as a powerful analytical strategy for
      systematic analysis and improved characterization of the major bioactive
      constituents from Radix Dipsaci.
AB  - Radix Dipsaci (RD), the dried root of Dipsacus asper, is commonly used as a
      traditional Chinese medicine for the treatment of bone diseases and functions in
      strengthening bone and healing bone fractures. Nevertheless, the high polarity,
      non chromophores and low abundance of multiple compounds in this plant bring
      difficulty for their isolation and structural determination by traditional
      chromatographic and spectroscopic techniques, which hindered the use of RD in
      clinical practice and retarded the process of RD modernization. In this work, a
      sensitive and rapid high-performance liquid chromatography coupled with
      electrospray time-of-flight-mass spectrometry (HPLC-ESI-QTOF-MS/MS) was employed
      to rapidly separate and identify the multiple minor constituents in RD.
      Separation was performed an Agilent poroshell 120 EC-C18 column (2.1mm*100mm,
      i.d., 2.7MUm) with 0.1% formic acid aqueous solution and acetonitrile as the
      mobile phase under gradient conditions. As a result, 36 major constituents
      including dipsacus saponins, iridoid glycosides and caffeoyl quinic acid
      derivatives were identified or tentatively characterized from the RD, 11 of which
      had not been previously reported to the best of our knowledge. In conclusion, the
      HPLC-ESI-QTOF-MS/MS is feasible and credible technique to separate and identify
      the constituents in complex matrices of traditional Chinese medicines. 

PMID- 24907651
TI  - Genetic and microscopic evidence for sexual reproduction in the centric diatom
      Skeletonema marinoi.
AB  - This study provides microscopic and molecular evidence for sexual reproduction in
      the homothallic centric diatom Skeletonema marinoi isolated from the Baltic Sea.
      The species is capable of restoring cell size asexually through an auxospore-like
      stage. However, cells were sexualized after shifting strains from low (6 PSU) to
      high (16 PSU) salinity. We observed flagellate male gametes and oogonia, with
      diameters of 3-4 and 3.2-6.3MUm, respectively. Fertilization took place followed
      by the formation of round auxospores surrounded by thin siliceous incunabular
      scales. Auxosporulation was synchronized, and a maximum of auxospores was
      detected on day three following the salinity shift. The proportion of auxospores
      to vegetative cells ranged from 0.02 to 0.18. There was a significant correlation
      between auxosporulation success and inoculum cell density. At lower cell
      concentration (5,000 cells ml(-1)), proportionally fewer auxospores were formed.
      Auxospores were formed in single strains and in crosses of strains. The
      proportion of auxospores differed significantly among strains and crosses of
      strains. Additionally, we isolated single auxospores, obtained F1 strains and
      performed microsatellite based pedigree analysis of parental generations and
      their offspring. We proved that the auxospores were formed sexually, either by
      inter- or by intra-strain fertilization.

PMID- 24907652
TI  - Nanochromosome copy number does not correlate with RNA levels though patterns are
      conserved between strains of the ciliate morphospecies Chilodonella uncinata.
AB  - In some ciliates, extensive genome fragmentation leads to a macronucleus (i.e.
      somatic nucleus) containing gene-sized chromosomes that vary in copy number. Yet
      the relationship between copy number and expression level is not well understood
      as previous work has shown a variety of patterns. For example, nanochromosome
      copy numbers are positively correlated to mRNA levels in spirotrichous ciliates,
      while one study of Chilodonella uncinata suggested that they were inversely
      correlated. To study further copy number and expression levels in C. uncinata, we
      analyzed 11 members in five gene families (SSU-rDNA, actin, alpha-tubulin,
      histidine acid phosphatase family protein and a protein kinase domain containing
      protein) from one strain. We find that macronuclear copy numbers of these genes
      range from hundreds to thousands per cell, and that copy number does not
      correlate with expression level as measured by steady-state RNA in predominantly
      vegetative cultures. We also compared six of these genes to their orthologs in a
      second genetically-isolated strain of C. uncinata to reveal that patterns of
      nanochromosome and transcript copy numbers are conserved between strains. Our
      data suggest that nanochromosome copy number may be related to a feature like
      nuclear architecture.

PMID- 24907653
TI  - Synthesis and functional characterization of a fluorescent peptide probe for non
      invasive imaging of collagen in live tissues.
AB  - Targeted molecular imaging to detect changes in the structural and functional
      organization of tissues, at the molecular level, is a promising approach for
      effective and early diagnosis of diseases. Quantitative and qualitative changes
      in type I collagen, which is a major component in the extra cellular matrix (ECM)
      of skin and other vital organs like lung, liver, heart and kidneys, are often
      associated with the pathophysiology of these organs. We have synthesized a
      fluorescent probe that comprises collagelin, a specific collagen binding peptide,
      coupled to fluorescent porphyrin that can effectively detect abnormal deposition
      of collagen in live tissues by emitting fluorescence in the near infra red (NIR)
      region. In this report we have presented the methodology for coupling of 5-(4
      carboxy phenyl)-10, 15, 20-triphenyl porphyrin (C-TPP) to the N-terminal of
      collagelin or to another mutant peptide (used as a control). We have evaluated
      the efficacy of these fluorescent peptides to detect collagen deposition in live
      normal and abnormal tissues. Our results strongly suggest that porphyrin-tagged
      collagelin can be used as an effective probe for the non invasive in vivo
      detection of tissue fibrosis, especially in the liver. 

PMID- 24907654
TI  - Laminin promotes vascular network formation in 3D in vitro collagen scaffolds by
      regulating VEGF uptake.
AB  - Angiogenesis is an essential neovascularisation process, which if recapitulated
      in 3D in vitro, will provide better understanding of endothelial cell (EC)
      behaviour. Various cell types and growth factors are involved, with vascular
      endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 key
      components. We were able to control the aggregation pattern of ECs in 3D collagen
      hydrogels, by varying the matrix composition and/or having a source of cells
      signalling angiogenic proteins. These aggregation patterns reflect the different
      developmental pathways that ECs take to form different sized tubular structures.
      Cultures with added laminin and thus increased expression of alpha6 integrin
      showed a significant increase (p<0.05) in VEGFR2 positive ECs and increased VEGF
      uptake. This resulted in the end-to-end network aggregation of ECs. In cultures
      without laminin and therefore low alpha6 integrin expression, VEGFR2 levels and
      VEGF uptake were significantly lower (p<0.05). These ECs formed contiguous
      sheets, analogous to the 'wrapping' pathway in development. We have identified a
      key linkage between integrin expression on ECs and their uptake of VEGF,
      regulated by VEGFR2, resulting in different aggregation patterns in 3D.

PMID- 24907655
TI  - Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells.
AB  - We investigated if the antileukemic drug idarubicin induces autophagy, a process
      of programmed cellular self-digestion, in leukemic cell lines and primary
      leukemic cells. Transmission electron microscopy and acridine orange staining
      demonstrated the presence of autophagic vesicles and intracellular acidification,
      respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased
      punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced
      the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of
      proteolysis inhibitors, and promoted the degradation of the selective autophagic
      target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited
      the phosphorylation of the main autophagy repressor mammalian target of rapamycin
      (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR
      activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin
      induced mTOR repression was associated with the activation of the mTOR inhibitor
      AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The
      suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1
      genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress,
      mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation.
      Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic
      cell line and leukocytes from chronic myeloid leukemia patients, but not healthy
      controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin
      treated leukemic cells, our results warrant caution when considering combining
      idarubicin with autophagy inhibitors in leukemia therapy. 

PMID- 24907656
TI  - EGF-FGF2 stimulates the proliferation and improves the neuronal commitment of
      mouse epidermal neural crest stem cells (EPI-NCSCs).
AB  - Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair
      follicles, are attractive candidates for several applications in cell therapy,
      drug screening and tissue engineering. As suggested remnants of the embryonic
      neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide
      variety of cell types and are readily accessible by a minimally invasive
      procedure. Since the combination of epidermal growth factor (EGF) and fibroblast
      growth factor type 2 (FGF2) is mitogenic and promotes the neuronal commitment of
      various stem cell populations, we examined its effects in the proliferation and
      neuronal potential of mouse EPI-NCSCs. By using a recognized culture protocol of
      bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs,
      characterized by the migratory potential, cell morphology and expression of
      phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth
      muscle markers and exhibited the NC-like fibroblastic morphology. The treatment
      with the combination EGF and FGF2, however, increased their proliferation rate
      and promoted the acquisition of a neuronal-like morphology accompanied by
      reorganization of neural cytoskeletal proteins betaIII-tubulin and nestin, as
      well as upregulation of the pan neuronal marker betaIII-tubulin and down
      regulation of the undifferentiated NC, glial and smooth muscle cell markers.
      Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic
      stimulation, as evidenced by induction of GAP43, and increased expression of Mash
      1 in neuron-like cell, both neuronal-specific proteins. Together, the results
      suggest that the combination of EGF-FGF2 stimulates the proliferation and
      improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES
      cells and neural progenitor/stem cells of the central nervous system and
      highlights the advantage of using EGF-FGF2 in neuronal differentiation protocols.

PMID- 24907657
TI  - Neuromodulation of neurons and synapses.
AB  - Neuromodulation underlies the flexibility of neural circuit operation and
      behavior. Individual neuromodulators can have divergent actions in a neuron by
      targeting multiple physiological mechanisms. Conversely, multiple neuromodulators
      may have convergent actions through overlapping targets. The divergent and
      convergent neuromodulator actions can be unambiguously synergistic or
      antagonistic, but neuromodulation often entails balanced adjustment of nonlinear
      membrane and synaptic properties by targeting ion channel and synaptic dynamics
      rather than just excitability or synaptic strength. In addition, neuromodulators
      can exert effects at multiple timescales, from short-term adjustments of neuron
      and synapse function to persistent long-term regulation. This short review
      summarizes some highlights of the diverse actions of neuromodulators on ion
      channel and synaptic properties. 

PMID- 24907658
TI  - Controlled release of transforming growth factor-beta3 from cartilage-extra
      cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue
      derived stem cells.
AB  - The objective of this study was to develop a scaffold derived from cartilaginous
      extracellular matrix (ECM) that could be used as a growth factor delivery system
      to promote chondrogenesis of stem cells. Dehydrothermal crosslinked scaffolds
      were fabricated using a slurry of homogenized porcine articular cartilage, which
      was then seeded with human infrapatellar-fat-pad-derived stem cells (FPSCs). It
      was found that these ECM-derived scaffolds promoted superior chondrogenesis of
      FPSCs when the constructs were additionally stimulated with transforming growth
      factor (TGF)-beta3. Cell-mediated contraction of the scaffold was observed, which
      could be limited by the additional use of 1-ethyl-3-3dimethyl aminopropyl
      carbodiimide (EDAC) crosslinking without suppressing cartilage-specific matrix
      accumulation within the construct. To further validate the utility of the ECM
      derived scaffold, we next compared its chondro-permissive properties to a
      biomimetic collagen-hyaluronic acid (HA) scaffold optimized for cartilage tissue
      engineering (TE) applications. The cartilage-ECM-derived scaffold supported at
      least comparable chondrogenesis to the collagen-HA scaffold, underwent less
      contraction and retained a greater proportion of synthesized sulfated
      glycosaminoglycans. Having developed a promising scaffold for TE, with superior
      chondrogenesis observed in the presence of exogenously supplied TGF-beta3, the
      final phase of the study explored whether this scaffold could be used as a TGF
      beta3 delivery system to promote chondrogenesis of FPSCs. It was found that the
      majority of TGF-beta3 that was loaded onto the scaffold was released in a
      controlled manner over the first 10days of culture, with comparable long-term
      chondrogenesis observed in these TGF-beta3-loaded constructs compared to
      scaffolds where the TGF-beta3 was continuously added to the media. The results of
      this study support the use of cartilage-ECM-derived scaffolds as a growth factor
      delivery system for use in articular cartilage regeneration. 

PMID- 24907659
TI  - Age-dependent regulation of tendon crimp structure, cell length and gap width
      with strain.
AB  - The black-and-white patterning of tendon fascicles when visualized by light
      microscopy, also known as crimp, is a well-known feature of fiber-forming
      collagens. However, not much is known about its development, function and
      response to strain. The objective of this study is to investigate the interaction
      of tenocyte and crimp morphology as well as their changes with increasing age and
      acute strain. In contrast to previous studies, which used indirect measures, such
      as polarized light, to investigate the crimp structure, this study visualizes
      internal crimp structure in three dimensions without freezing, sectioning,
      staining or fixing the tissue, via two-photon imaging of green fluorescent
      protein expressing cells within mouse tail tendon fascicles. This technique
      further allows straining of the live tissue while visualizing changes in crimp
      morphology and cell shape with increasing specimen length. Combining this novel
      microscopy technique with computational image and data analysis revealed a
      complex relationship between tenocytes and the extracellular matrix that evolves
      with increasing age. While the reduction of crimping with strain was observed as
      expected, most of the crimps were gone at 0-1% strain already. Even relatively
      low strains of 3% led to pronounced changes in the crimp structure after
      relaxation, particularly in the young animals, which could not be seen with
      bright-field imaging. Cell length and gap width increased with strain. However,
      while the cells were able to return to their original length even after high
      strains of 6%, the gaps between the cells widened, which may imply modified cell
      cell communication after overstretching. 

PMID- 24907660
TI  - Evaluation of skeletal tissue repair, part 2: enhancement of skeletal tissue
      repair through dual-growth-factor-releasing hydrogels within an ex vivo chick
      femur defect model.
AB  - There is an unmet need for improved, effective tissue engineering strategies to
      replace or repair bone damaged through disease or injury. Recent research has
      focused on developing biomaterial scaffolds capable of spatially and temporally
      releasing combinations of bioactive growth factors, rather than individual
      molecules, to recapitulate repair pathways present in vivo. We have developed an
      ex vivo embryonic chick femur critical size defect model and applied the model in
      the study of novel extracellular matrix (ECM) hydrogel scaffolds containing
      spatio-temporal combinatorial growth factor-releasing microparticles and skeletal
      stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels
      combined with poly(d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10
      30% PDLLGA-PEG-PLDLGA) microparticles releasing dual combinations of vascular
      endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3
      (TGF-beta3) and the bone morphogenetic protein BMP2, with human adult Stro-1+bone
      marrow stromal cells (HBMSCs), were placed into 2mm central segmental defects in
      embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with
      VEGF combinations induced host cell migration and type I collagen deposition.
      Combinations of TGF-beta3/BMP2, particularly with Stro-1+HBMSCs, induced
      significant formation of structured bone matrix, evidenced by increased Sirius
      red-stained matrix together with collagen expression demonstrating birefringent
      alignment within hydrogels. This study demonstrates the successful use of the
      chick femur organotypic culture system as a high-throughput test model for
      scaffold/cell/growth factor therapies in regenerative medicine. Temporal release
      of dual growth factors, combined with enriched Stro-1+HBMSCs, improved the
      formation of a highly structured bone matrix compared to single release
      modalities. These studies highlight the potential of a unique alginate/bECM
      hydrogel dual growth factor release platform for bone repair. 

PMID- 24907661
TI  - The Osteoprint: a bioinspired two-photon polymerized 3-D structure for the
      enhancement of bone-like cell differentiation.
AB  - The need for a better understanding of cell behavior and for exploiting cell
      functions in various healthcare applications has driven biomedical research to
      develop increasingly complex fabrication strategies to reproduce the natural
      biological microenvironment in vitro. Different approaches have led to the
      development of refined examples of 2- and 3-D structures able to sustain cellular
      proliferation, differentiation and functionality very similar to those normally
      occurring in living organisms. One such approach is two-photon polymerization. In
      this paper, we present a trabecula-like structure (which we have named
      "Osteoprint") that resembles to the typical microenvironment of trabecular bone
      cells. Starting from microtomography images of the trabecular bone, we prepared
      several Osteoprints through two-photon polymerization and tested the behavior of
      SaOS-2 bone-like cells cultured on our structures. Interestingly, we found that
      Osteoprints deeply affect cellular behavior, determining an exit from the cell
      cycle and an enhancement of osteogenic differentiation. Indeed, we found an up
      regulation of the genes involved in SaOS-2 cell maturation and an increase in
      hydroxyapatite production and accumulation upon SaOS-2 culture on the
      Osteoprints. The findings we obtained are extremely interesting, and open up new
      perspectives in "bioinspired" approaches for tissue engineering and regenerative
      medicine. 

PMID- 24907662
TI  - Nuclear distribution of claudin-2 increases cell proliferation in human lung
      adenocarcinoma cells.
AB  - Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines,
      although it is absent in normal lung tissue. However, the role of claudin-2 in
      cell proliferation and the regulatory mechanism of intracellular distribution
      remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased
      by claudin-2 knockdown together with a decrease in the percentage of S phase
      cells. This knockdown decreased the expression levels of ZONAB and cell cycle
      regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma
      tissues and proliferating A549 cells. The nuclear distribution of ZONAB and
      percentage of S phase cells were higher in cells exogenously expressing claudin-2
      with a nuclear localization signal than in cells expressing claudin-2 with a
      nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and
      cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of
      claudin-2, was higher than that of wild type. We suggest that nuclear
      distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2
      serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement
      of cell proliferation in lung adenocarcinoma cells. 

PMID- 24907663
TI  - Subcellular compartmentation of ascorbate and its variation in disease states.
AB  - Beyond its general role as antioxidant, specific functions of ascorbate are
      compartmentalized within the eukaryotic cell. The list of organelle-specific
      functions of ascorbate has been recently expanded with the epigenetic role
      exerted as a cofactor for DNA and histone demethylases in the nucleus.
      Compartmentation necessitates the transport through intracellular membranes;
      members of the GLUT family and sodium-vitamin C cotransporters mediate the
      permeation of dehydroascorbic acid and ascorbate, respectively. Recent
      observations show that increased consumption and/or hindered entrance of
      ascorbate in/to a compartment results in pathological alterations partially
      resembling to scurvy, thus diseases of ascorbate compartmentation can exist. The
      review focuses on the reactions and transporters that can modulate ascorbate
      concentration and redox state in three compartments: endoplasmic reticulum,
      mitochondria and nucleus. By introducing the relevant experimental and clinical
      findings we make an attempt to coin the term of ascorbate compartmentation
      disease. 

PMID- 24907665
TI  - Consideration of the factors that can influence a new point-of-care testing
      system for measuring white blood cell and C-reactive protein levels in blood.

PMID- 24907666
TI  - Flow cytometry-based analysis by Sysmex-UF1000i(r) is an alternative method in
      the assessment of periodontal inflammation.
AB  - BACKGROUND: Gingivitis is a common inflammatory condition. We explored the value
      of flow cytometry of saliva in patients with periodontal inflammation. METHODS: A
      cohort of 249 healthy adults (age range: 18-81 y; 2.5th to 97.5th percentile: 19
      66 y) was investigated for caries, dental plaque and gingivitis. Saliva was
      analyzed using flow cytometry on a Sysmex UF-1000i(r). RESULTS: Sysmex UF
      1000i(r) is capable to reproduce reliable measurements of cellular components in
      saliva. A statistically significant lower number of salivary bacteria was found
      in patients with gingivitis in comparison with healthy adults (p<0.0001). A
      significant difference in salivary leukocyte count was found between patients
      with different gingival index scores (p<0.0005). The gingivitis score was
      strongly dependent on the number of salivary leukocytes, the age of the patient
      and the degree of caries and dental plaque (r(2)=0.60, p<0.001). At a cut-off
      level of 10(3) leukocytes/MUl saliva, an area under the curve of 0.82 was
      obtained with a sensitivity of 76% and a specificity of 78% in patients (>35 y)
      with a gingivitis score of 3. CONCLUSION: Flow cytometry is an alternative method
      to evaluate local inflammatory processes in the mouth with a sensitivity of 76%
      and a specificity of 78%.

PMID- 24907664
TI  - Autophagy and human disease: emerging themes.
AB  - Malfunction of autophagy, the process that mediates breakdown and recycling of
      intracellular components in lysosomes, has been linked to a variety of human
      diseases. As the number of pathologies associated with defective autophagy
      increases, emphasis has switched from the mere description of the status of
      autophagy in these conditions to a more mechanistic dissection of the autophagic
      changes. Understanding the reasons behind the autophagic defect, the immediate
      consequences of the autophagic compromise and how autophagy changes with the
      evolution of the disease has become a 'must,' especially now that manipulation of
      autophagy is being considered as a therapeutic strategy. Here, we comment on some
      of the common themes that have emerged from such detailed analyses of the
      interplay between autophagy and disease conditions. 

PMID- 24907667
TI  - Annexin A1 concentrations is decreased in patients with diabetes type 2 and
      nephropathy.

PMID- 24907668
TI  - Modeling a phosphorus credit trading program in an agricultural watershed.
AB  - Water quality and economic models were linked to assess the economic and
      environmental benefits of implementing a phosphorus credit trading program in an
      agricultural sub-basin of Lake Okeechobee watershed, Florida, United States. The
      water quality model determined the effects of rainfall, land use type, and
      agricultural management practices on the amount of total phosphorus (TP)
      discharged. TP loadings generated at the farm level, reaching the nearby streams,
      and attenuated to the sub-basin outlet from all sources within the sub-basin,
      were estimated at 106.4, 91, and 85 mtons yr(-)(1), respectively. Almost 95% of
      the TP loadings reaching the nearby streams were attributed to agriculture
      sources, and only 1.2% originated from urban areas, accounting for a combined TP
      load of 87.9 mtons yr(-)(1). In order to compare a Least-Cost Abatement approach
      to a Command-and-Control approach, the most cost effective cap of 30% TP
      reduction was selected, and the individual allocation was set at a TP load target
      of 1.6 kg ha(-1) yr(-1) (at the nearby stream level). The Least-Cost Abatement
      approach generated a potential cost savings of 27% ($1.3 million per year), based
      on an optimal credit price of $179. Dairies (major buyer), ornamentals, row
      crops, and sod farms were identified as potential credit buyers, whereas citrus,
      improved pastures (major seller), and urban areas were identified as potential
      credit sellers. Almost 81% of the TP credits available for trading were
      exchanged. The methodology presented here can be adapted to deal with different
      forms of trading sources, contaminants, or other technologies and management
      practices. 

PMID- 24907669
TI  - Impacts of tourism hotspots on vegetation communities show a higher potential for
      self-propagation along roads than hiking trails.
AB  - Vegetation communities along recreational tracks may suffer from substantial edge
      effects through the impacts of trampling, modified environmental conditions and
      competition with species that benefit from disturbance. We assessed impacts on
      trackside vegetation by comparing high and low usage tourism sites at a 1-10 m
      distance from recreational tracks in a popular arid-lands tourism destination in
      South Australia. The central aim was quantification of the strengths and spatial
      extent of tourism impacts along recreational tracks with a qualitative comparison
      of roads and trails. Track-distance gradients were most prevalent at high usage
      sites. There, species community composition was altered, total plant cover
      decreased, non-native species cover increased, plant diversity increased or
      decreased (depending on the distance) and soil compaction increased towards
      recreational tracks. Roadside effects were greater and more pervasive than
      trailside effects. Further, plant diversity did not continuously increase towards
      the road verge as it did along trails but dropped sharply in the immediate road
      shoulder which indicated high disturbance conditions that few species were able
      to tolerate. To our knowledge, we are the first to demonstrate that the access
      mode to a recreation site influences the potential of certain impacts, such as
      the increase of non-native species, to self-perpetuate from their points of
      introduction to disjointed sites with a predisposition to disturbance. Due to
      this propulsion of impacts, the overall spatial extent of roadside impacts was
      far greater than initially apparent from assessments at the road verge. We
      discuss possible means of mitigating these impacts. 

PMID- 24907670
TI  - Insights into the population structure of Mycobacterium tuberculosis using
      spoligotyping and RDRio in a southeastern Brazilian prison unit.
AB  - Tuberculosis (TB) is still a serious public health problem, continuing to be an
      important threat for confined populations. We used spoligotyping to estimate the
      genotypic clades of Mycobacterium tuberculosis isolates from inmates in two
      blocks in a southeastern Brazilian prison unit, with TB incidence rate of
      8185/100.000. The Latin American Mediterranean (LAM) clade is well represented in
      the country, and the LAM specific molecular markers, RD(Rio) large sequence
      polymorphism and the SNP on the Rv3062 [ligB(1212)], were used to characterize
      spoligotype signatures from prison isolates. Typing of RD(Rio) and ligB increase
      LAM clade from 66.7% (n=72/108) to 69.4% (n=75). The LAM2 SIT17 (n=23) and SIT179
      (n=12) signatures comprised one third of all isolates, followed by Haarlem
      (11.5%, n=12), T (8.7%, n=9) and X (5.7%, n=6) clades. Strains with unknown
      signatures represented 5.5% (n=6), and four (3.7%) did not match any lineage. We
      observed RD(Rio) among 64 (59.2%) isolates, and 54 (50%) were of the LAM clade.
      In particular, the LAM2/RD(Rio) sub-lineage was significantly associated with
      clustering (p=0.02) and its frequency was higher (32%) when compared to that of
      the previous general TB cases in RJ (4.29%). Overall cluster frequency defined by
      spoligotyping/IS6110-RFLP was 62%. The two evolutionary markers helped to
      evaluate some LAM signature misconceptions and demonstrate that LAM2/RD(Rio) was
      found with high frequency, hitherto being unnoticed. All these data, allied to
      high clustering, imply that public health measures to minimize the escalation of
      TB in prison is essential, and both spoligotyping as well as RD(Rio) would be
      useful tools to monitor the effects of the measures with respect to M.
      tuberculosis lineage variation. 

PMID- 24907671
TI  - Numerical modelling of the mechanical behaviour of an osteon with microcracks.
AB  - In this work, we present two strategies for the numerical modelling of
      microcracks and damage within an osteon. A numerical model of a single osteon
      under compressive diametral load is developed, including lamellae organized
      concentrically around the haversian canal and the presence of lacunae. Elastic
      properties have been estimated from micromechanical models that consider the
      mineralized collagen fibrils reinforced with hydroxyapatite crystals and the
      dominating orientation of the fibrils in each lamella. Microcracks are simulated
      through the node release technique, enabling propagation along the lamellae
      interfaces by application of failure criteria initially conceived for composite
      materials, in particular the Brewer and Lagace criterion for delamination. A
      second approach is also presented, which is based on the progressive degradation
      of the stiffness at the element level as the damage increases. Both strategies
      are discussed, showing a good agreement with experimental evidence reported by
      other authors. It is concluded that interlaminar shear stresses are the main
      cause of failure of an osteon under compressive diametral load. 

PMID- 24907672
TI  - A revised and unified pressure-clamp/relaxation theory for studying plant cell
      water relations with pressure probes: in-situ determination of cell volume for
      calculation of volumetric elastic modulus and hydraulic conductivity.
AB  - The cell-pressure-probe is a unique tool to study plant water relations in-situ.
      Inaccuracy in the estimation of cell volume (nuo) is the major source of error in
      the calculation of both cell volumetric elastic modulus (epsilon) and cell
      hydraulic conductivity (Lp). Estimates of nuo and Lp can be obtained with the
      pressure-clamp (PC) and pressure-relaxation (PR) methods. In theory, both methods
      should result in comparable nuo and Lp estimates, but this has not been the case.
      In this study, the existing nuo-theories for PC and PR methods were reviewed and
      clarified. A revised nuo-theory was developed that is equally valid for the PC
      and PR methods. The revised theory was used to determine nuo for two extreme
      scenarios of solute mixing between the experimental cell and sap in the pressure
      probe microcapillary. Using a fully automated cell-pressure-probe (ACPP) on leaf
      epidermal cells of Tradescantia virginiana, the validity of the revised theory
      was tested with experimental data. Calculated nuo values from both methods were
      in the range of optically determined nuo (=1.1-5.0nL) for T. virginiana. However,
      the PC method produced a systematically lower (21%) calculated nuo compared to
      the PR method. Effects of solute mixing could only explain a potential error in
      calculated nuo of <3%. For both methods, this discrepancy in nuo was almost
      identical to the discrepancy in the measured ratio of DeltaV/DeltaP (total change
      in microcapillary sap volume versus corresponding change in cell turgor) of 19%,
      which is a fundamental parameter in calculating nuo. It followed from the revised
      theory that the ratio of DeltaV/DeltaP was inversely related to the solute
      reflection coefficient. This highlighted that treating the experimental cell as
      an ideal osmometer in both methods is potentially not correct. Effects of non
      ideal osmotic behavior by transmembrane solute movement may be minimized in the
      PR as compared to the PC method. 

PMID- 24907673
TI  - Ancestral inference in tumors: how much can we know?
AB  - A tumor is thought to start from a single cell and genome. Yet genomes in the
      final tumor are typically heterogeneous. The mystery of this intratumoral
      heterogeneity (ITH) has not yet been uncovered, but much of this ITH may be
      secondary to replication errors. Methylation of cytosine bases often exhibits ITH
      and therefore may encode the ancestry of the tumor. In this study, we measure the
      passenger methylation patterns of a specific CpG region in 9 colorectal tumors by
      bisulfite sequencing and apply a tumor development model. Based on our model, we
      are able to retrieve information regarding the ancestry of each tumor using
      approximate Bayesian computation. With a large simulation study we explore the
      conditions under which we can estimate the model parameters, and the initial
      state of the first transformed cell. Finally we apply our analysis to clinical
      data to gain insight into the dynamics of tumor formation. 

PMID- 24907674
TI  - Serotonergic pathways in the Drosophila larval enteric nervous system.
AB  - The enteric nervous system is critical for coordinating diverse feeding-related
      behaviors and metabolism. We have characterized a cluster of four serotonergic
      neurons in Drosophila larval brain: cell bodies are located in the subesophageal
      ganglion (SOG) whose neuronal processes project into the enteric nervous system.
      Electrophysiological, calcium imaging and behavioral analyses indicate a
      functional role of these neurons in modulating foregut motility. We suggest that
      the axonal projections of this serotonergic cluster may be part of a brain-gut
      neural pathway that is functionally analogous to the vertebrate vagus nerve. 

PMID- 24907675
TI  - Spotting the differences: probing host/microbiota interactions with a dedicated
      software tool for the analysis of faecal outputs in Drosophila.
AB  - The intestinal physiology of Drosophila melanogaster can be monitored in an
      integrative, non-invasive manner by analysing graphical features of the excreta
      produced by flies fed on a dye-supplemented diet. This assay has been used by
      various labs to explore gut function and its regulation. To facilitate its use,
      we present here a free, stand-alone dedicated software tool for the analysis of
      fly excreta. The Ultimate Reader of Dung (T.U.R.D.) is designed to offer a
      flexible environment for a wide range of experimental designs, with special
      attention to automation and high-throughput processing. This software detects the
      distinctive changes in acid-base and water balance previously reported to occur
      in response to dietary challenges and mating. We have used T.U.R.D. to test the
      contribution of the bacterial environment of the flies to various intestinal
      parameters including the established diet- and mating-triggered responses. To
      this end, we have analysed the faecal patterns of flies reared in germ-free
      conditions, upon re-association with controlled microbiota and subjected to food
      borne or systemic, non-lethal bacterial infections. We find that the tested
      faecal outputs are unchanged in all these conditions, suggesting that the impact
      of the bacterial environment on the intestinal features highlighted by faecal
      deposit analysis is minimal. 

PMID- 24907676
TI  - Irreversible inhibitory kinetics of mercuric ion on N-acetyl-beta-D
      glucosaminidase from Nile tilapia (Oreochromis niloticus).
AB  - N-acetyl-beta-D-glucosaminidase (EC 3.2.1.52, NAGase), hydrolyzes dimers or
      trimers of N-acetyl-beta-D-glucosamine (NAG) into monomers and is shown to be
      important for the reproduction of male animals. NAGase is purified from the
      spermary of Nile tilapia, and its enzyme activity can be strongly inhibited by
      mercuric chloride (HgCl2). In this paper, we determined the kinetics of HgCl2
      mediated inhibition of NAGase, and our results showed that it was irreversible
      inhibition with an IC50 value at 2.70+/-0.02 MUM. Moreover, Hg(2+) reduced the
      thermal and pH stability of the enzyme. We determined the inhibition kinetics of
      Hg(2+) by using the kinetic method of substrate reaction. With this inhibition
      model, the microscopic rate constants for the reaction of Hg(2+) with free enzyme
      (k1) and the enzyme-substrate complex ( [Formula: see text] ) were determined to
      be 4.42*10(-4) mM(-1) s(-1) and 7.06*10(-5) mM(-1) s(-1), respectively,
      indicating that the presence of substrate can protect NAGase from Hg(2+)
      inhibition.

PMID- 24907677
TI  - Multiple cueing dissociates location- and feature-based repetition effects.
AB  - There is an extensive literature on the phenomenon of inhibition of return (IOR):
      When attention is drawn to a peripheral location and then removed, response time
      is delayed if a target appears in the previously inspected location. Recent
      research suggests that non-spatial attribute repetition (i.e., if a target shares
      a feature like color with the earlier, cueing, stimulus) can have a similar
      inhibitory effect, at least when the target appears in the previously cued
      location. What remains unknown is whether location- and feature-based inhibitory
      effects can be dissociated. In the present study, we used a multiple cueing
      approach to investigate the properties of location- and feature-based repetition
      effects. In two experiments (detection, and discrimination), location-based IOR
      was absent but feature-based inhibition was consistently observed. Thus, the
      present results indicate that feature- and location-based inhibitory effects are
      dissociable. The results also provide support for the view that the attentional
      consequences of multiple cues reflect the overall center of gravity of the cues.
      We suggest that the repetition costs associated with feature and location
      repetition may be best understood as a consequence of the pattern of activation
      for object files associated with the stimuli present in the displays. 

PMID- 24907678
TI  - An efficient method of exploring simulation models by assimilating literature and
      biological observational data.
AB  - Recently, several biological simulation models of, e.g., gene regulatory networks
      and metabolic pathways, have been constructed based on existing knowledge of
      biomolecular reactions, e.g., DNA-protein and protein-protein interactions.
      However, since these do not always contain all necessary molecules and reactions,
      their simulation results can be inconsistent with observational data. Therefore,
      improvements in such simulation models are urgently required. A previously
      reported method created multiple candidate simulation models by partially
      modifying existing models. However, this approach was computationally costly and
      could not handle a large number of candidates that are required to find models
      whose simulation results are highly consistent with the data. In order to
      overcome the problem, we focused on the fact that the qualitative dynamics of
      simulation models are highly similar if they share a certain amount of regulatory
      structures. This indicates that better fitting candidates tend to share the basic
      regulatory structure of the best fitting candidate, which can best predict the
      data among candidates. Thus, instead of evaluating all candidates, we propose an
      efficient explorative method that can selectively and sequentially evaluate
      candidates based on the similarity of their regulatory structures. Furthermore,
      in estimating the parameter values of a candidate, e.g., synthesis and
      degradation rates of mRNA, for the data, those of the previously evaluated
      candidates can be utilized. The method is applied here to the pharmacogenomic
      pathways for corticosteroids in rats, using time-series microarray expression
      data. In the performance test, we succeeded in obtaining more than 80% of
      consistent solutions within 15% of the computational time as compared to the
      comprehensive evaluation. Then, we applied this approach to 142 literature
      recorded simulation models of corticosteroid-induced genes, and consequently
      selected 134 newly constructed better models. The method described here was found
      to be capable of efficiently exploring candidate simulation models and obtaining
      better models within a short span of time. Furthermore, the results suggest that
      there may be room for improvement in literature recorded pathways and that they
      can be systematically updated using biological observational data. 

PMID- 24907679
TI  - The influence of amorphization methods on the apparent solubility and dissolution
      rate of tadalafil.
AB  - This study for the first time investigates the solubility and dissolution rate of
      amorphous tadalafil (Td)--a poorly water soluble chemical compound which is
      commonly used for treating the erectile dysfunction. To convert the crystalline
      form of Td drug to its amorphous counterpart we have employed most of the
      commercially available amorphization techniques i.e. vitrification, cryogenic
      grinding, ball milling, spray drying, freeze drying and antisolvent
      precipitation. Among the mentioned methods only quenched cooling of the molten
      sample was found to be an inappropriate method of Td amorphization. This is due
      to the thermal decomposition of Td above 200 degrees C, as proved by the
      thermogravimetric analysis (TGA). Disordered character of all examined samples
      was confirmed using differential scanning calorimetry (DSC) and X-ray powder
      diffraction (PXRD). In the case of most amorphous powders, the largest 3-fold
      increase of apparent solubility was observed after 5 min, indicating their fast
      recrystallization in water. On the other hand, the partially amorphous
      precipitate of Td and hypromellose enhanced the solubility of Td approximately 14
      times, as compared with a crystalline substance, which remained constant for half
      an hour. Finally, disk intrinsic dissolution rate (DIDR) of amorphous forms of Td
      was also examined.

PMID- 24907680
TI  - A novel concentration dependent amino acid ion pair strategy to mediate drug
      permeation using indomethacin as a model insoluble drug.
AB  - Assessment of oral drug bioavailability is an important parameter for new
      chemical entities (NCEs) in drug development cycle. After evaluating the
      pharmacological response of these new molecules, the following critical stage is
      to investigate their in vitro permeability. Despite the great success achieved by
      prodrugs, covalent linking the drug molecule with a hydrophobic moiety might
      result in a new entity that might be toxic or ineffective. Therefore, an
      alternative that would improve the drug uptake without affecting the efficacy of
      the drug molecule would be advantageous. The aim of the current study is to
      investigate the effect of ion-pairing on the permeability profile of a model
      drug: indomethacin (IND) to understand the mechanism behind the permeability
      improvement across Caco-2 monolayers. Arginine and lysine formed ion-pairs with
      IND at various molar ratios 1:1, 1:2, 1:4 and 1:8 as reflected by the double
      reciprocal graphs. The partitioning capacities of the IND were evaluated using
      octanol/water partitioning studies and the apparent permeabilities (Papp) were
      measured across Caco-2 monolayers for the different formulations. Partitioning
      studies reflected the high hydrophobicity of IND (LogP=3) which dropped upon
      increasing the concentrations of arginine/lysine in the ion pairs. Nevertheless,
      the prepared ion pairs improved IND permeability especially after 60 min of the
      start of the experiment. Coupling partitioning and permeability results suggest a
      decrease in the passive transcellular uptake due to the drop in IND portioning
      capacities and a possible involvement of active carriers. Future work will
      investigate which transport gene might be involved in the absorption of the ion
      paired formulations using molecular biology technologies.

PMID- 24907681
TI  - Development of Recombinant Human Growth Hormone (rhGH) sustained-release
      microspheres by a low temperature aqueous phase/aqueous phase emulsion method.
AB  - A novel method has been developed to protect Recombinant Human Growth Hormone
      (rhGH) in poly (lactic-co-glycolic acid) (PLGA) microspheres using an aqueous
      phase/aqueous phase emulsion and S/O/W multi-emulsion method. This method
      develops a novel rhGH sustained-release system, which is based on the combination
      of rhGH-loaded dextran microparticles and PLGA microspheres. The process to
      fabricate rhGH-loaded dextran microparticles involves an aqueous phase/aqueous
      phase emulsion system formed at the reduced temperature. RhGH was first dissolved
      in water together with dextran and polyethylene glycol, followed by stirring at
      the speed of 2000 rpm for 20-30s at 0 degrees C, and then a freezing process
      could enable the dextran phase to separate from the continuous PEG phase and rhGH
      could preferentially be loaded with dextran. The sample after freezing and phase
      separation was then lyophilized to powder and washed with dichloromethane to
      remove the PEG. Once loaded in the dextran microparticles (1-4 MUm in diameter),
      rhGH gained resistance to interface tensions and was encapsulated into PLGA
      microspheres without aggregation thereafter. RhGH released from PLGA microspheres
      was in a sustained manner with minimal burst and maximally reduced incomplete
      release in vitro. Single subcutaneous injection of rhGH-loaded PLGA microspheres
      to rats resulted in a stable plasma concentration for 30 days avoiding the drug
      concentration fluctuations after multiple injections of protein solutions. In a
      hypophysectomized rat model, the IGF-1 and bodyweight results showed that there
      were higher than the levels obtained for the sustained release formulation by
      W/O/W for 40 days. These results suggest that the microsphere delivery system had
      the potential to be an injectable depot for sustained-release of the
      biocompatible protein of rhGH.

PMID- 24907682
TI  - Novel pyrazolopyrimidine derivatives targeting COXs and iNOS enzymes; design,
      synthesis and biological evaluation as potential anti-inflammatory agents.
AB  - A novel set of 4-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidine and 5-substituted
      1-phenyl-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and
      evaluated as potential anti-inflammatory agents. The newly prepared compounds
      were assessed through the examination of their in vitro inhibition of four
      targets; cyclooxygenases subtypes (COX-1 and COX-2), inducible nitric oxide
      synthase (iNOS) and nuclear factor kappa B (NF-kappaB). Compounds 8a, 10c and 13c
      were the most potent and selective ligands against COX-2 with inhibition
      percentages of 79.6%, 78.7% and 78.9% at a concentration of 2 MUM respectively,
      while compound 13c significantly inhibited both COX subtypes. On the other hand,
      fourteen compounds showed high iNOS inhibitory activities with IC50 values in the
      range of 0.22-8.5MUM where the urea derivative 11 was the most active compound
      with IC50 value of 0.22 MUM. Most of the tested compounds were found to be devoid
      of inhibitory activity against NF-kB. Moreover, almost all compounds were not
      cytotoxic, (up to 25 MUg/ml), against a panel of normal and cancer cell lines.
      The in silico docking results were in agreement with the in vitro inhibitory
      activities against COXs and iNOS enzymes. The results of in vivo anti
      inflammatory and antinociceptive studies were consistent with that of in vitro
      studies which confirmed that compounds 8a, 10c and 13c have significant anti
      inflammatory and analgesic activities comparable to that of the control,
      ketorolac. Taken together, dual inhibition of COXs and iNOS with novel
      pyrazolopyrimidine derivatives is a valid strategy for the development of anti
      inflammatory/analgesic agents with the probability of fewer side effects.

PMID- 24907683
TI  - Preparation and quantification of radioactive particles for tracking hydrodynamic
      behavior in multiphase reactors.
AB  - Radioactive particle tracking (RPT) has emerged as a promising and versatile
      technique that can provide rich information about a variety of multiphase flow
      systems. However, RPT is not an off-the-shelf technique, and thus, users must
      customize RPT for their applications. This paper presents a simple procedure for
      preparing radioactive tracer particles created via irradiation with neutrons from
      the TRIGA Mark II research reactor. The present study focuses on the performance
      evaluation of encapsulated gold and scandium particles for applications as
      individual radioactive tracer particles using qualitative and quantitative
      neutron activation analysis (NAA) and an X-ray microcomputed tomography (X-ray
      Micro-CT) scanner installed at the Malaysian Nuclear Agency. 

PMID- 24907684
TI  - Comment on "Design and bioevaluation of a 32P-patch for brachytherapy of skin
      diseases" [Appl. Radiat. Isot. 66 (2008) 303-309].

PMID- 24907685
TI  - Advances in processes for PET radiotracer synthesis: separation of [18F]fluoride
      from enriched [18O]water.
AB  - Positron emission tomography (PET) is a powerful scientific and clinical tool for
      the study and visualization of human physiology that can provide important
      information about metabolism and diseases such as cancer. At present,
      [(18)F]fluorodeoxyglucose ([(18)F]FDG) is the most frequently used radiotracer
      for the routine clinical evaluation of malignant tumors in a range of body
      tissues. FDG synthesis is continuously being developed to improve and simplify
      the synthetic procedure including the isolation of [(18)F]fluoride from
      [(18)O]water. There are many methods reported in literature for the isolation of
      [(18)F]fluoride, including evaporation, coat-capture-elution, the use of cation
      exchange resin and electrode trapping. This review article gives an overview of
      some of the most common methods for the separation of [(18)F]fluoride ions from
      [(18)O]water, highlighting the potential strength of the methods and also
      problems and weaknesses for synthesis of (18)F PET tracers. 

PMID- 24907686
TI  - Connecting combat-related mild traumatic brain injury with posttraumatic stress
      disorder symptoms through brain imaging.
AB  - Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may
      share common symptom and neuropsychological profiles in military service members
      (SMs) following deployment; while a connection between the two conditions is
      plausible, the relationship between them has been difficult to discern. The
      intent of this report is to enhance our understanding of the relationship between
      findings on structural and functional brain imaging and symptoms of PTSD. Within
      a cohort of SMs who did not meet criteria for PTSD but were willing to complete a
      comprehensive assessment within 2 months of their return from combat deployment,
      we conducted a nested case-control analysis comparing those with combat-related
      mTBI to age/gender-matched controls with diffusion tensor imaging, resting state
      functional magnetic resonance imaging and a range of psychological measures. We
      report degraded white matter integrity in those with a history of combat mTBI,
      and a positive correlation between the white matter microstructure and default
      mode network (DMN) connectivity. Higher clinician-administered and self-reported
      subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings
      offer a potential mechanism through which mTBI may alter brain function, and in
      turn, contribute to PTSD symptoms. 

PMID- 24907687
TI  - Long-term differential effects of chronic young-adult corticosterone exposure on
      anxiety and depression-like behaviour in BDNF heterozygous rats depend on the
      experimental paradigm used.
AB  - Brain-derived neurotrophic factor (BDNF) has key roles in neurodevelopment and
      synaptic plasticity and is implicated in affective disorders such as anxiety and
      depression. The aim of the present study was to use BDNF heterozygous mutant rats
      (HET) and wildtype controls (WT) to investigate the effect of BDNF downregulation
      on affective behaviours. We also assessed the longterm effects of young-adult
      stress, here simulated by chronic corticosterone (CORT) treatment. This treatment
      reduced anxiety-like behaviour in BDNF HET rats on the plus-maze but not in the
      open-field. There were no genotype or CORT effects on immobility time in the
      forced swim test. These results show differential effects of CORT treatment on
      anxiety-like behaviour in BDNF HET rats which were dependent on the experimental
      paradigms used. While these results do not negate the potential of BDNF HET rats
      in studies on the role of BDNF in affective disorders, caution is needed about
      experimental details and the choice of paradigms used. 

PMID- 24907688
TI  - Immediate and long-term consequences of vascular toxicity during zebrafish
      development.
AB  - Proper formation of the vascular system is necessary for embryogenesis, and
      chemical disruption of vascular development may be a key event driving
      developmental toxicity. In order to test the effect of environmental chemicals on
      this critical process, we evaluated a quantitative assay in transgenic zebrafish
      using angiogenesis inhibitors that target VEGFR2 (PTK787) or EGFR (AG1478). Both
      PTK787 and AG1478 exposure impaired intersegmental vessel (ISV) sprouting, while
      AG1478 also produced caudal and pectoral fin defects at concentrations below
      those necessary to blunt ISV morphogenesis. The functional consequences of vessel
      toxicity during early development included decreased body length and survival in
      juvenile cohorts developmentally exposed to inhibitor concentrations sufficient
      to completely block ISV sprouting angiogenesis. These data show that
      concentration-dependent disruption of the presumed targets for these inhibitors
      produce adverse outcomes at advanced life stages. 

PMID- 24907689
TI  - Effects of varying the inter-meal interval on relationships between antral area,
      gut hormones and energy intake following a nutrient drink in healthy lean humans.
AB  - The aim of this study was to determine: (i) the effects of varying the inter-meal
      interval on subsequent energy intake, and (ii) temporal relationships between
      postprandial changes in antral area and gastrointestinal hormone concentrations
      with energy intake. 16 healthy lean participants (10 M, 6 F) were studied on 4
      occasions in randomized fashion. Participants consumed 500ml of water 180min
      ("control"), or 500ml of a mixed-nutrient drink (750kcal) 30 ("EI-30"), 90 ("EI
      90") or 180 ("EI-180") min, prior to a cold, buffet-style meal, from which energy
      intake was quantified. Antral area was measured using 2D-ultrasound, perceptions
      of hunger and fullness were scored using visual analogue scales, and blood
      samples collected at regular intervals for analysis of plasma cholecystokinin
      (CCK), peptide YY (PYY) and ghrelin concentrations. All nutrient drinks increased
      antral area, stimulated CCK and PYY, and suppressed ghrelin and energy intake (EI
      30: -367+/-69, EI-90: -291+/-69, EI-180: -219+/-72kcal, P<0.05, for all),
      compared with control. Energy intake was related directly to the length of the
      inter-meal interval (R=0.33, P<0.01), such that as the inter-meal interval
      increased, energy intake increased. There was a strong relationship between
      antral area (R=-0.76, P<0.001), and weaker relationships between CCK (R=-0.36,
      P<0.01) and PYY (R=-0.34, P<0.01), with the inter-meal interval. In conclusion,
      energy intake increased as the inter-meal interval increased. This was associated
      with temporal changes in gastric content (antral area) and plasma gut hormone
      concentrations. 

PMID- 24907690
TI  - Developmental differences in the effects of alcohol and stress on heart rate
      variability.
AB  - Adolescent rats differ in their responses to stress and ethanol from their adult
      counterparts, although not much is known about the contribution of the autonomic
      nervous system (ANS) to these differences. This study assessed the impact of
      stress, ethanol, and their combination on parameters of heart rate variability
      (HRV) in adolescent and adult male Sprague-Dawley rats. Animals were habituated
      to the testing box and neck sensors (MouseOX, STARR Life Sciences Corp.) used for
      recording heart rate (HR). After 8-10min of baseline recording, animals were
      restrained for 90min or returned home, followed by intraperitoneal injection of
      0, 0.5, 1.0, or 1.5g/kg ethanol. The 8-10min test recording occurred 30min post
      injection. Ethanol-related decreases in LF (an index of sympathetic activity)
      were evident under non-stressed conditions in adolescents but only after stress
      in adults, perhaps in part due to apparent ethanol-induced sympathetic
      deactivation in adolescents. Parasympathetic tone, indexed by HF, was unaffected
      by both ethanol and stress in adolescents, while again both the 1.0 and 1.5g/kg
      ethanol doses decreased HF in adults following stress. Ethanol also decreased low
      frequency/high frequency tone (LF/HF), an index of sympathovagal balance, only in
      adolescents, with no decrease evident in adults. Further, stressed adults, and
      not adolescents, had significantly lower CORT and PROG values than their non
      stressed counterparts. Taken together, these results demonstrate notable age
      differences in the ANS response to ethanol under stressful vs. non-stressful
      circumstances, reflected by ethanol-mediated autonomic effects that were more
      pronounced following stressor exposure in adults but under non-stressed
      conditions in adolescents. 

PMID- 24907691
TI  - Can architectural design alter the physiological reaction to psychosocial stress?
      A virtual TSST experiment.
AB  - Is has long been established, that views to natural scenes can a have a dampening
      effect on physiological stress responses. However, as people in Europe, Canada
      and North America today spent 50-85% of their time indoors, attention might also
      be paid to how the artificial man-made indoor environment influences these
      mechanisms. The question that this study attempts to start addressing is
      therefore whether certain design, characteristics of indoor spaces can make a
      difference to the physiological stress response as well. Using a virtual version
      of the Trier Social Stress Test, in which the space is computer generated and
      properties of the space therefore can be systematically varied, we measured
      saliva cortisol and heart rate variability in participants in a closed room
      versus a room with openings. As shown by a significant linear contrast
      interaction between groups and TSST conditions, participants in the closed room
      responded with more pronounced cortisol reactivity to stress induction, and
      continued to show higher levels throughout recovery, compared to participants in
      the open room. No differences were found regarding any part of the autonomic
      nervous system. 

PMID- 24907692
TI  - Behavioural and physiological indicators of shelter dogs' welfare: reflections on
      the no-kill policy on free-ranging dogs in Italy revisited on the basis of 15
      years of implementation.
AB  - The Italian National Law 281 of 1991 forbids the euthanatization of free-ranging
      dogs, unless they have an incurable illness or are proved to be dangerous.
      Without neglecting the undeniable benefits of the "no-kill" policy, nevertheless
      it has brought about a chronic overpopulation in shelters and, as a result,
      higher costs of management and welfare problems since some dogs remain in the
      shelter for life. In 2004-2008, the Istituto Zooprofilattico Sperimentale of the
      Lazio and Tuscany regions carried out a survey in the Lazio Region to verify the
      effects of the Italian National Law 281/91 on free-ranging dog management
      following 15 years from its implementation. One of the aims of the study was an
      assessment of the welfare of dogs in a shelter sample (8 shelters out of 47
      censused in the Lazio Region). 97 mixed-breed dogs were selected, their behaviour
      was studied and a blood sample was taken for each dog in order to determine the
      individual blood concentration of cortisol and the amount of oxidative damage
      (level of dRoms), as well as the amount of antioxidants to cope with it.
      Moreover, the total leukocyte count (leukogram) was accomplished. We ran general
      backward stepwise regression models using "level of antioxidant", "level of
      dRoms" and "level of serum cortisol" as dependent variables respectively. The
      results showed that the most important variable that improved the level of
      welfare of dogs consisted in having the opportunity to regularly go out of the
      cage for a walk, whereas other variables like gender, size of the cage (small,
      medium, large), being alone in the cage, and being neutered/entire, had no
      significant effect on the physiological indicators of welfare. Dogs that enjoyed
      the regular walk had a higher total antioxidant capacity, and performed a lower
      frequency of displacing activities and stereotyped behaviour. Moreover, oxidative
      stress parameters seem to be indicators well matched with behavioural indicators
      of stress. Thus, for the first time, markers of oxidative status are utilised for
      the welfare evaluation in the domestic dog. Furthermore, the results of this
      paper give some suggestion about how small steps can help to improve shelters
      and, furthermore, this paper intends to solicit the debate on the no-kill policy.

PMID- 24907693
TI  - Juvenile stress affects anxiety-like behavior and limbic monoamines in adult
      rats.
AB  - Epidemiological evidence suggests that childhood and adolescent maltreatment is a
      major risk factor for mood disorders in adulthood. However, the mechanisms
      underlying the manifestation of mental disorders during adulthood are not well
      understood. Using a recently developed rat model for assessing chronic variable
      stress (CVS) during early adolescence (juvenility), we investigated the long-term
      effects of juvenile CVS on emotional and cognitive function and on monoaminergic
      activities in the limbic areas. During juvenility (postnatal days 27-33), rats in
      the stress group were exposed to variable stressors every other day for a week.
      Four weeks later, anhedonia was tested in the sucrose test, anxiety-like
      behaviors were assessed in the elevated plus-maze (EPM) and open field (OF)
      tests, and cortically mediated cognitive function was evaluated during an
      attentional set-shifting task (AST). After the behavioral tests, the rats were
      decapitated to determine limbic monoamine and metabolite levels. Adult rats
      stressed during juvenility exhibited higher anxiety-like behaviors, as evidenced
      by reduced locomotion and rearing behavior in the OF and fewer entries into the
      open arms in the EPM. There were no differences between the stressed rats and the
      controls in depressive-like anhedonia during the sucrose preference test or in
      cognitive function during the AST test in adulthood. In addition, the previously
      stressed rats exhibited increased dopamine (DA) and decreased 5-HIAA in the
      medial prefrontal cortex (mPFC) and decreased noradrenaline in the amygdala
      compared with controls. Furthermore, DA levels in the mPFC were correlated with
      adult anxious behaviors in the OF. These results suggest that juvenile stress
      induces long-term changes in the expression of anxiety-like behaviors and limbic
      monoaminergic activity in adult rats. 

PMID- 24907694
TI  - Personality correlates (BAS-BIS), self-perception of social ranking, and cortical
      (alpha frequency band) modulation in peer-group comparison.
AB  - The perception and interpretation of social hierarchies are a key part of our
      social life. In the present research we considered the activation of cortical
      areas, mainly the prefrontal cortex, related to social ranking perception in
      conjunction with some personality components (BAS - Behavioral Activation System 
      and BIS - Behavioral Inhibition System). In two experiments we manipulated the
      perceived superior/inferior status during a competitive cognitive task. Indeed,
      we created an explicit and strongly reinforced social hierarchy based on
      incidental rating in an attentional task. Specifically, a peer group comparison
      was undertaken and improved (Experiment 1) or decreased (Experiment 2)
      performance was artificially manipulated by the experimenter. For each experiment
      two groups were compared, based on a BAS and BIS dichotomy. Alpha band modulation
      in prefrontal cortex, behavioral measures (performance: error rate, ER; response
      times, RTs), and self-perceived ranking were considered. Repeated measures ANOVAs
      and regression analyses showed in Experiment 1 a significant improved cognitive
      performance (decreased ER and RTs) and higher self-perceived ranking in high-BAS
      participants. Moreover, their prefrontal activity was increased within the left
      side (alpha band decreasing). Conversely, in Experiment 2 a significant decreased
      cognitive performance (increased ER and RTs) and lower self-perceived ranking was
      observed in higher-BIS participants. Their prefrontal right activity was
      increased in comparison with higher BAS. The regression analyses confirmed the
      significant predictive role of alpha band modulation with respect of subjects'
      performance and self-perception of social ranking, differently for BAS/BIS
      components. The present results suggest that social status perception is directly
      modulated by cortical activity and personality correlates. 

PMID- 24907695
TI  - The effect of daily caffeine exposure on lever-pressing for sucrose and c-Fos
      expression in the nucleus accumbens in the rat.
AB  - Recent reports suggest that caffeine exposure increases the motivation to consume
      drugs of abuse. As such, it may also enhance the motivation to consume palatable
      food. Because caffeine is a common constituent in over-the-counter weight-loss
      supplements, it is important to better understand the relationship between
      caffeine and food intake. The purpose of this study was to measure the effects of
      daily intermittent caffeine exposure on lever pressing for sucrose in rats and to
      assess the impact of caffeine on neuronal activation in the nucleus accumbens
      (NAc). Male Sprague-Dawley rats that received either saline or caffeine (1, 5,
      20mg/kgi.p.) daily were tested on a fixed ratio 4 schedule for sucrose in operant
      chambers for 10days and then again following a 5-day treatment withdrawal period.
      After behavioral testing, a subset of the animals was sacrificed to measure the
      impact of caffeine on neuronal activation in the NAc using c-Fos as a marker.
      There was a significant increase in active lever presses for sucrose in the rats
      that had received 5mg/kg of caffeine when compared with the saline group. This
      treatment effect was no longer present after the withdrawal period. Acute, but
      not chronic, caffeine exposure elevated c-Fos expression in the NAc. These data
      suggest that intermittent daily caffeine exposure increases lever pressing for
      sucrose in rats, but leaves no lasting effect. 

PMID- 24907696
TI  - Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle
      dependent manner.
AB  - The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its
      rodent intermediate host to facilitate its passage to its feline definitive host.
      This is accomplished by a reduction of the aversive response that rodents show
      towards cat odors, which likely increases the predation risk. Females on average
      show similar changes as males. However, behaviors that relate to aversion and
      attraction are usually strongly influenced by the estrus cycle. In this study, we
      replicated behavioral effects of T. gondii in female rats, as well as expanded it
      to two novel behavioral paradigms. We also characterized the role of the estrus
      cycle in the behavioral effects of T. gondii on female rats. Uninfected females
      preferred to spend more time in proximity to rabbit rather than bobcat urine, and
      in a dark chamber rather than a lit chamber. Infected females lost both of these
      preferences, and also spent more time investigating social novelty (foreign
      bedding in their environment). Taken together, these data suggest that infection
      makes females less risk averse and more exploratory. Furthermore, this effect was
      influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat
      urine throughout the cycle except at estrus and metestrus. In contrast, infected
      rats lost this preference at every stage of the cycle except estrus. Commensurate
      with the possibility that this was a hormone-dependent effect, infected rats had
      elevated levels of circulating progesterone, a known anxiolytic. 

PMID- 24907697
TI  - Gender-dependent effect on nociceptive response induced by chronic variable
      stress.
AB  - It has previously been reported that exposure to repeated restraint stress
      induces hyperalgesia in male rats, an effect that was not observed in females.
      The aim of the present study was to investigate the effects of chronic variable
      stress over 40days on nociception threshold indexed by tail-flick latency in male
      and female adult rats. The results showed different behavior in chronically
      stressed animals when compared to the control group: male rats showed a decrease
      in tail-flick latency while females presented an increase in this parameter. For
      female rats this effect was independent of the phase of the estrous cycle.
      Several sources of data indicate that behavioral and physiological responses to
      stress are sexually dimorphic, including in nociception, and the estrous cycle
      appears to be a factor that influences opioid analgesia in female. These effects
      are modulated by the strain and conditions of nociception assay. Additional
      studies concerning the mechanisms involved in the hyperalgesic response in males
      and the differences on nociceptive response in females chronically exposed to
      stress are needed. 

PMID- 24907698
TI  - Behavioral and EEG changes in male 5xFAD mice.
AB  - Transgenic animal models of Alzheimer's disease (AD) are widely used to
      investigate mechanisms of pathophysiology and cognitive dysfunctions. A model
      with a very early development of parenchymal plaque load at the age of 2months is
      the 5xFAD mouse (Tg6799, Oakley et al. 2006). These 5xFAD mice over-express both
      human amyloid precursor protein (APP) and human presenilin 1 (PS1). Mice from
      this line have a high APP expression correlating with a high burden and an
      accelerated accumulation of the 42 amino acid species of amyloid-beta (Abeta).
      The aim of this study was the behavioral and functional investigations of 5xFAD
      males because in most studies females of this strain were characterized. In
      comparison to literature of transgenic 5xFAD females, transgenic 5xFAD males
      showed decreased anxiety in the elevated plus maze, reduced locomotion and
      exploration in the open field and disturbances in learning performance in the
      Morris water maze starting at 9months of age. Electroencephalogram (EEG)
      recordings on 6month old transgenic mice revealed a decrease of delta, theta,
      alpha, beta and gamma frequency bands whereas the subdelta frequency was
      increased. EEG recordings during sleep showed a reduction of rapid eye movement
      sleep in relation to the amount of total sleep. Thus, 5xFAD males develop early
      functional disturbances and subsequently behavioral deficits and therefore they
      are a good mouse model for studying Alzheimer's disease. 

PMID- 24907699
TI  - The relationship between obstetricians' cognitive and affective traits and their
      patients' delivery outcomes.
AB  - OBJECTIVE: The objective of the study was to investigate the relationship between
      physician coping skills, need for cognition, tolerance of ambiguity, and anxiety
      and their patients' mode of delivery. STUDY DESIGN: Ninety-four obstetricians
      were surveyed using 5 standardized psychometric scales: Reflective Coping,
      Proactive Coping, Multiple Stimulus Types Ambiguity Tolerance-II, Need for
      Cognition (measures learner motivation and engagement in cognitive efforts), and
      State-Trait Anxiety Inventory. Psychometric test scores were analyzed by
      quartile. Data regarding route of delivery were collected on 3488 nulliparous,
      term, cephalic, nonanomalous singleton deliveries performed by participating
      physicians. chi(2) tests and random-effects logistic regression analyses were
      used to examine the relationship between the obstetrician cognitive traits and
      type of delivery. RESULTS: Sixty-one percent of the women were delivered by
      spontaneous vaginal delivery, 15.5% by operative vaginal delivery, and 23.5% by
      cesarean delivery. Random-effects multivariable logistic regression adjusting for
      patient characteristics demonstrated that physicians with the most reflective
      coping (ie, highest quartile) were significantly less likely (adjusted odds
      ratio, 0.70; 95% confidence interval, 0.50-0.98) to perform operative vaginal
      delivery. However, lower anxiety and higher ambiguity tolerance were associated
      with an increased risk of chorioamnionitis and postpartum hemorrhage,
      respectively. There were no identified differences in adverse neonatal outcomes
      by physician cognitive or affective traits. CONCLUSION: There is a decreased risk
      of operative vaginal delivery for patients delivered by providers with better
      adaptive decision-making traits. Other cognitive and affective traits were
      associated with a greater chance of chorioamnionitis and hemorrhage. Further work
      is required to elucidate whether training in these cognitive and affective traits
      can alter obstetric outcomes.

PMID- 24907700
TI  - Progression of ultrasound findings of fetal syphilis after maternal treatment.
AB  - OBJECTIVE: The purpose of this study was to evaluate ultrasound findings of fetal
      syphilis and to describe their progression after maternal treatment. STUDY
      DESIGN: This was a retrospective cohort study from September 1981 to June 2011 of
      seropositive women after 18 weeks of gestation who had an ultrasound before
      treatment to evaluate for fetal syphilis. Only those women who received treatment
      after the initial ultrasound scan, but before delivery, were included. If the
      initial ultrasound scan was abnormal, serial sonography was performed until
      resolution of the abnormality or delivery. Patient demographics, ultrasound
      findings, stage of syphilis, delivery, and infant outcomes were recorded.
      Standard statistical analyses were performed. Kaplan-Meier estimates were
      constructed to estimate time to resolution. RESULTS: Two hundred thirty-five
      women met the inclusion criteria; 73 of them (30%) had evidence of fetal syphilis
      on initial ultrasound scan. Abnormalities included hepatomegaly (79%),
      placentomegaly (27%), polyhydramnios (12%), ascites (10%) and abnormal middle
      cerebral arterial Doppler assessment (33%). After treatment, middle cerebral
      arterial Doppler assessment abnormalities, ascites, and polyhydramnios resolved
      first, followed by placentomegaly and finally hepatomegaly. Infant outcomes were
      available for 173 deliveries; of these, 32 infants (18%) were diagnosed with
      congenital syphilis. Congenital syphilis was more common when antenatal
      ultrasound abnormalities were present (39% vs 12%; P < .001). Infant examination
      findings at delivery were similar between women with and without an abnormal
      pretreatment ultrasound scan. However, in those infants with congenital syphilis,
      hepatomegaly was the most frequent abnormality found, regardless of antenatal
      ultrasound findings. CONCLUSION: Sonographic signs of fetal syphilis confer a
      higher risk of congenital syphilis at delivery for all maternal stages.
      Hepatomegaly develops early and resolves last after antepartum treatment.

PMID- 24907701
TI  - The role of cervical length in women with threatened preterm labor: is it a valid
      predictor at any gestational age?
AB  - OBJECTIVE: To determine whether the predictive accuracy of sonographic cervical
      length (CL) for preterm delivery (PTD) in women with threatened preterm labor
      (PTL) is related to gestational age (GA) at presentation. STUDY DESIGN: A
      retrospective cohort study of all women with singleton pregnancies who presented
      with PTL at less than 34 + 0 weeks and underwent sonographic measurement of CL in
      a tertiary medical center between 2007 and 2012. The predictive accuracy of CL
      for PTD was stratified by GA at presentation. RESULTS: Overall, 1077 women who
      presented with PTL have had sonographic measurement of CL and met the study
      inclusion criteria. Of those, 223 (20.7%) presented at 24 + 0-26 + 6 weeks (group
      1), 274 (25.4%) at 27 + 0-29 + 6 weeks (group 2), 283 (26.3%) at 30 + 0-31 + 6
      weeks (group 3), and 297 (27.6%) at 32 + 0-33 + 6 weeks (group 4). The overall
      performance CL as a predictive test for PTD was similar in the 4 GA groups, as
      reflected by the similar degree of correlation between CL with the examination to
      delivery interval (r = 0.27, r = 0.26, r = 0.28, and r = 0.29, respectively, P =
      .8), the similar area under the receiver-operator characteristic curve (0.641
      0.690, 0.631-0.698, 0.643-0.654, and 0.678-0.698, respectively, P = .7), and a
      similar decrease in the risk of PTD of 5-10% for each additional millimeter of
      CL. The optimal cutoff of CL, however, was affected by GA at presentation, so
      that a higher cutoff of CL was needed to achieve a target negative predictive
      value for delivery within 14 days from presentation for women who presented later
      in pregnancy. The optimal thresholds to maximize the negative predictive value
      for delivery within 14 days were 36 mm, 32.5 mm, 24 mm and 20.5 mm for women who
      presented at 32 + 0 to 33 + 6 weeks, 30 + 0 to 31 + 6 weeks, 27 + 0 to 29 + 6
      weeks and 24 + 0 to 26 + 6, respectively. CONCLUSION: CL has modest predictive
      accuracy in women with threatened PTL, regardless of GA at presentation. However,
      the optimal cutoff of CL for the purpose of clinical decision making in women
      with PTL needs to be adjusted based on GA at presentation.

PMID- 24907702
TI  - Nonreassuring fetal status during trial of labor after cesarean.
AB  - OBJECTIVE: Concern for uterine rupture has led to the decline in vaginal births
      after cesarean. Nonreassuring fetal status (NRFS) may precede uterine rupture.
      The objective of this study was to estimate the risks of uterine rupture, uterine
      dehiscence, and adverse fetal outcomes associated with NRFS during trial of labor
      after cesarean (TOLAC). STUDY DESIGN: In a retrospective cohort study of the
      previously reported Maternal-Fetal Medicine Units Network prospective cohort
      cesarean registry, we compared women undergoing repeat cesarean for NRFS after
      TOLAC to those requiring repeat cesarean for other intrapartum indications.
      Exclusion criteria included women with a prior cesarean who underwent elective or
      indicated repeat cesarean or women with a multiple gestation. Primary outcomes
      included uterine rupture or dehiscence. Secondary outcomes included 5-minute
      Apgar score <7 and neonatal intensive care unit admission. Planned subanalyses
      for term and preterm deliveries were performed. Stratified and logistic
      regression analyses were used. RESULTS: Of 17,740 women undergoing TOLAC, 4754
      (26.8%) had a failed vaginal birth after cesarean. Of those, NRFS was the primary
      indication for cesarean in 1516 (31.9%). Women with NRFS as the primary
      indication for repeat cesarean were at increased risk of uterine rupture
      (adjusted odds ratio, 3.32; 95% confidence interval, 2.21-5.00), uterine
      dehiscence (adjusted odds ratio, 1.70; 95% confidence interval, 1.09-2.65), 5
      minute Apgar score <7, and neonatal intensive care unit admission compared to
      women with other primary indications. CONCLUSION: Women attempting TOLAC who
      require repeat cesarean for NRFS are at increased risk of uterine rupture and
      uterine dehiscence.

PMID- 24907703
TI  - Guided outcomes in learned efficiency model in clinical medical education: a
      randomized controlled trial of self-regulated learning.
AB  - OBJECTIVE: The guided outcomes in learned efficiency (GOLE) model emphasizes the
      use of evidence-based resources to understand the diagnosis, treatment, follow
      up, and prevention of disease. We seek to determine whether presentations created
      using the GOLE model are superior to an unstructured approach in achieving
      Accreditation Council for Graduate Medical Education (ACGME) Core Competencies.
      STUDY DESIGN: Consenting medical students were randomized to GOLE or control
      groups to individually research a self-selected clinical topic. A validated
      survey instrument was used prepresentation and postpresentation to assess
      perceived improvement in knowledge. Subjects completed self-evaluations at
      enrollment and after presentation of their chosen clinical topic. Other students,
      residents, and a faculty member also completed evaluations after each student
      presentation. Standard statistical methods (analysis of variance, 2-tailed t
      test) were used to determine if a statistically significant difference existed
      between intervention and control groups. RESULTS: Self-assessments were similar
      in the GOLE and control groups. Externally perceived presentation scores were
      greater in the GOLE group (ACGME global P < .0001, presentation global P = .07),
      which demonstrated a significant improvement in 5 core competencies. Time spent
      preparing the presentation and resources utilized did not differ between groups.
      CONCLUSION: The presentations prepared using the GOLE model were rated higher by
      observers than those prepared using traditional techniques.

PMID- 24907705
TI  - Biomagnetic monitoring as a validation tool for local air quality models: a case
      study for an urban street canyon.
AB  - Biomagnetic monitoring of tree leaf deposited particles has proven to be a good
      indicator of the ambient particulate concentration. The objective of this study
      is to apply this method to validate a local-scale air quality model (ENVI-met),
      using 96 tree crown sampling locations in a typical urban street canyon. To the
      best of our knowledge, the application of biomagnetic monitoring for the
      validation of pollutant dispersion modeling is hereby presented for the first
      time. Quantitative ENVI-met validation showed significant correlations between
      modeled and measured results throughout the entire in-leaf period. ENVI-met
      performed much better at the first half of the street canyon close to the ring
      road (r=0.58-0.79, RMSE=44-49%), compared to second part (r=0.58-0.64, RMSE=74
      102%). The spatial model behavior was evaluated by testing effects of height,
      azimuthal position, tree position and distance from the main pollution source on
      the obtained model results and magnetic measurements. Our results demonstrate
      that biomagnetic monitoring seems to be a valuable method to evaluate the
      performance of air quality models. Due to the high spatial and temporal
      resolution of this technique, biomagnetic monitoring can be applied anywhere in
      the city (where urban green is present) to evaluate model performance at
      different spatial scales. 

PMID- 24907704
TI  - Associations between ambient air pollution and blood markers of inflammation and
      coagulation/fibrinolysis in susceptible populations.
AB  - The pathophysiological pathways linking particulate air pollution to
      cardiovascular disease are still not fully understood. We examined the
      association between ambient air pollutants and blood markers of inflammation and
      coagulation/fibrinolysis in three potentially susceptible populations. Three
      panels of non-smoking individuals were examined between 3/2007 and 12/2008: 1)
      with type 2 diabetes mellitus (T2D, n=83), 2) with impaired glucose tolerance
      (IGT, n=104), and 3) with a potential genetic predisposition which could affect
      detoxifying and inflammatory pathways (n=87) defined by the null polymorphism for
      glutathione S-transferase M1 (GSTM1) in combination with a certain single
      nucleotide polymorphism on the C-reactive protein (CRP) or the fibrinogen gene.
      Study participants had blood drawn up to seven times every four to six weeks. In
      total, 1765 blood samples were analysed for CRP, interleukin (IL)-6, soluble CD40
      ligand (sCD40L), fibrinogen, myeloperoxidase (MPO), and plasminogen activator
      inhibitor-1 (PAI-1). Hourly mean values of particulate air pollutants, particle
      number concentrations in different size ranges and gaseous pollutants were
      collected at fixed monitoring sites and individual 24hour averages calculated.
      Associations between air pollutants and blood markers were analysed for each
      panel separately and taking the T2D panel and the IGT panel together, using
      additive mixed models adjusted for long-term time trend and meteorology. For the
      panel with potential genetic susceptibility, CRP and MPO increased for most lags,
      especially with the 5-day average exposure (% change of geometric mean and 95%
      confidence interval: 22.9% [12.0;34.7] for CRP and 5.0% [0.3;9.9] for MPO per
      interquartile range of PM2.5). Small positive associations were seen for
      fibrinogen while sCD40L, PAI-1 and IL-6 mostly decreased in association with air
      pollution concentrations. Except for positive associations for fibrinogen we did
      not see significant results with the two other panels. Participants with
      potential genetic susceptibility showed a clear association between inflammatory
      blood biomarkers and ambient air pollutants. Our results support the hypothesis
      that air pollution increases systemic inflammation especially in susceptible
      populations which may aggravate atherosclerotic diseases and induce multi-organ
      damage. 

PMID- 24907706
TI  - Numerical simulation on the long-term variation of radioactive cesium
      concentration in the North Pacific due to the Fukushima disaster.
AB  - Numerical simulations on oceanic (134)Cs and (137)Cs dispersions were intensively
      conducted in order to assess an effect of the radioactive cesium on the North
      Pacific environment with a focus on the long-term variation of the radioactive
      cesium concentration after the Fukushima disaster that occurred in March 2011.
      The amounts of (134)Cs and (137)Cs released into the ocean were estimated using
      oceanic monitoring data, whereas the atmospheric deposition was calculated
      through atmospheric dispersion simulations. The highly accurate ocean current
      reanalyzed through a three-dimensional variational data assimilation enabled us
      to clarify the time series of the (134)Cs and (137)Cs concentrations in the North
      Pacific. It was suggested that the main radioactive cesium cloud due to the
      direct oceanic release reached the central part of the North Pacific, crossing
      170 degrees W one year after the Fukushima disaster. The radioactive cesium was
      efficiently diluted by meso-scale eddies in the Kuroshio Extension region and its
      concentration in the surface, intermediate, and deep layers had already been
      reduced to the pre-Fukushima background value in the wide area within the North
      Pacific 2.5 years after the Fukushima disaster. 

PMID- 24907707
TI  - Logistic analysis of epidemiologic studies with augmentation sampling involving
      re-stratification and population expansion.
AB  - Epidemiologic cross-sectional, case-cohort, or case-control studies often select
      augmentation samples to supplement an existing (baseline) sample, primarily for
      the two reasons: (1) to increase the sample sizes from certain subdomains of
      interest that were not originally considered in the design of the baseline study
      and (2) to obtain samples from an extension of the target population. To address
      these two objectives, two-stage stratified sample designs are considered, where
      the stratification based on the expanded population at the second stage is not
      nested in the first stage strata. The sample weighting and Taylor linearization
      variance estimation for the two-stage stratified sample designs, involving re
      stratification and population expansion, are provided for estimating population
      totals and logistic regression coefficients. Results from limited simulation
      studies and a logistic regression analysis of a study of human papillomavirus
      serology are provided. 

PMID- 24907708
TI  - Improving upon the efficiency of complete case analysis when covariates are MNAR.
AB  - Missing values in covariates of regression models are a pervasive problem in
      empirical research. Popular approaches for analyzing partially observed datasets
      include complete case analysis (CCA), multiple imputation (MI), and inverse
      probability weighting (IPW). In the case of missing covariate values, these
      methods (as typically implemented) are valid under different missingness
      assumptions. In particular, CCA is valid under missing not at random (MNAR)
      mechanisms in which missingness in a covariate depends on the value of that
      covariate, but is conditionally independent of outcome. In this paper, we argue
      that in some settings such an assumption is more plausible than the missing at
      random assumption underpinning most implementations of MI and IPW. When the
      former assumption holds, although CCA gives consistent estimates, it does not
      make use of all observed information. We therefore propose an augmented CCA
      approach which makes the same conditional independence assumption for missingness
      as CCA, but which improves efficiency through specification of an additional
      model for the probability of missingness, given the fully observed variables. The
      new method is evaluated using simulations and illustrated through application to
      data on reported alcohol consumption and blood pressure from the US National
      Health and Nutrition Examination Survey, in which data are likely MNAR
      independent of outcome. 

PMID- 24907709
TI  - Interaction of di-N-acetylchitobiosyl moranoline with a family GH19 chitinase
      from moss, Bryum coronatum.
AB  - Tri-N-acetylchitotriosyl moranoline, (GlcNAc)3-M, was previously shown to
      strongly inhibit lysozyme (Ogata M, Umemoto N, Ohnuma T, Numata T, Suzuki A, Usui
      T, Fukamizo T. 2013. A novel transition-state analogue for lysozyme, 4-O-beta-tri
      Nacetylchitotriosyl moranoline, provided evidence supporting the covalent
      glycosyl-enzyme intermediate. J Biol Chem. 288:6072-6082). The findings prompted
      us to examine the interaction of di-N-acetylchitobiosyl moranoline, (GlcNAc)2-M,
      with a family GH19 chitinase from moss, Bryum coronatum (BcChi19A). Thermal
      unfolding experiments using BcChi19A and the catalytic acid-deficient mutant
      (BcChi19A-E61A) revealed that the transition temperature (Tm) was elevated by 4.3
      and 5.8 degrees C, respectively, upon the addition of (GlcNAc)2-M, while the
      chitin dimer, (GlcNAc)2, elevated Tm only by 1.0 and 1.4 degrees C, respectively.
      By means of isothermal titration calorimetry, binding free energy changes for the
      interactions of (GlcNAc)3 and (GlcNAc)2-M with BcChi19A-E61A were determined to
      be -5.2 and -6.6 kcal/mol, respectively, while (GlcNAc)2 was found to interact
      with BcChi19A-E61A with markedly lower affinity. nuclear magnetic resonance
      titration experiments using (15)N-labeled BcChi19A and BcChi19A-E61A revealed
      that both (GlcNAc)2 and (GlcNAc)2-M interact with the region surrounding the
      catalytic center of the enzyme and that the interaction of (GlcNAc)2-M is
      markedly stronger than that of (GlcNAc)2 for both enzymes. However, (GlcNAc)2-M
      was found to moderately inhibit the hydrolytic reaction of chitin
      oligosaccharides catalyzed by BcChi19A (IC50 = 130-620 MUM). A molecular dynamics
      simulation of BcChi19A in complex with (GlcNAc)2-M revealed that the complex is
      quite stable and the binding mode does not significantly change during the
      simulation. The moranoline moiety of (GlcNAc)2-M did not fit into the catalytic
      cleft (subsite -1) but was rather in contact with subsite +1. This situation may
      result in the moderate inhibition toward the BcChi19A-catalyzed hydrolysis. 

PMID- 24907710
TI  - Utility of recombinant proteins LID-1 and PADL in screening for Mycobacterium
      leprae infection and leprosy.
AB  - BACKGROUND: Despite the widespread use of multidrug therapy, leprosy remains an
      important public health concern in many regions. Detection is generally limited
      to clinical exam. METHODS: As a two-tiered active case finding strategy, we used
      the LID-1 (leprosy IDRI diagnostic-1), and PADL (protein advances for the
      diagnosis of leprosy) antigens for serological examination of 2526 individuals
      randomly selected from 10 472 residents in a leprosy hyperendemic area
      (Cajazeiras, Paraiba, Brazil). Almost all seropositive (95%) and a subset of
      seronegative (17%) subjects then underwent clinical evaluations. RESULTS:
      Prevalence of clinically apparent leprosy was 2.3% (19 cases among 834 fully
      examined individuals). LID-1 and PADL demonstrated a high sensitivity for
      supporting leprosy diagnosis at 89% and 87%, with positive predictive values
      (PPV) of 3.5% and 3.7%. The specificity for clinically apparent leprosy was low
      at 42% and 38%, respectively, and was likely reduced due to the presence of many
      asymptomatic individuals infected with Mycobacterium leprae. CONCLUSIONS: Our
      data indicate the utility of the LID-1 and PADL antigens as primary screening
      tools for the detection of M. leprae infection and identification of leprosy
      patients. The follow-up of seropositive subjects could clarify the predictive
      value and utility of detecting anti-LID-1 and PADL antibodies within leprosy
      control programs.

PMID- 24907711
TI  - Comparison of four methods for extracting DNA from dried blood on filter paper
      for PCR targeting the mitochondrial Plasmodium genome.
AB  - BACKGROUND: Few studies comparing multiple methods for DNA extraction from dried
      blood spots (DBS) on filter paper for PCR targeting the Plasmodium genome have
      been done. METHODS: Frequently-used methods for DNA extraction from DBS using
      Chelex-100, InstaGene Matrix, QIAamp DNA Mini Kit and TE buffer were compared on
      a dilution series of a standardized Plasmodium falciparum positive sample. The
      two DNA extraction methods resulting in the lowest limits of detection were
      compared by testing both on 31 P. falciparum positive samples collected under
      field conditions and stored for 4 years. RESULTS: The Chelex-100, InstaGene
      Matrix and QIAamp DNA Mini Kit methods performed similarly, resulting in the
      detection of 0.5 to 2 parasites per microliter (p/ul). The same 13 clinical
      samples (13/31; 42%) were positive using both DNA extraction methods with the
      lowest limits of detection. CONCLUSIONS: Simple and low-cost methods can be
      sensitive and useful in extracting DNA from DBS. Poor results on stored clinical
      DBS indicate that further studies on the impact of storage duration and
      conditions, and choice of filter paper should be performed.

PMID- 24907712
TI  - The effects of season and meteorology on human mortality in tropical climates: a
      systematic review.
AB  - Research in the field of atmospheric science and epidemiology has long recognized
      the health effects of seasonal and meteorological conditions. However, little
      scientific knowledge exists to date about the impacts of atmospheric parameters
      on human mortality in tropical regions. Working within the scope of this
      systematic review, this investigation conducted a literature search using
      different databases; original research articles were chosen according to pre
      defined inclusion and exclusion criteria. Both seasonal and meteorological
      effects were considered. The findings suggest that high amounts of rainfall and
      increasing temperatures cause a seasonal excess in infectious disease mortality
      and are therefore relevant in regions and populations in which such diseases are
      prevalent. On the contrary, moderately low and very high temperatures exercise an
      adverse effect on cardio-respiratory mortality and shape the mortality pattern in
      areas and sub-groups in which these diseases are dominant. Atmospheric effects
      were subject to population-specific factors such as age and socio-economic status
      and differed between urban and rural areas. The consequences of climate change as
      well as environmental, epidemiological and social change (e.g., emerging non
      communicable diseases, ageing of the population, urbanization) suggest a growing
      relevance of heat-related excess mortality in tropical regions. 

PMID- 24907714
TI  - Performance of different carbonaceous materials for emerging pollutants
      adsorption.
AB  - The adsorption of three representative emerging pollutants over different kinds
      of carbonaceous adsorbents has been studied in this work. The adsorbates were
      nalidixic acid (NAL, representative of a pharmaceutical), 1,8-dichlorooctane
      (DCO, a chloroparaffin) and methyl-phenoxy-ethanol (MPET, a surfactant).
      Activated carbons, carbon nanofibers, carbon nanotubes and high surface area
      graphites have been tested as adsorbents. Adsorption isotherms, carried out in a
      batch system, were fitted using both a Langmuir and a Freundlich model. It was
      shown that the capacity of adsorption follows the order DCO?NAL>MPET for all the
      adsorbents, and among the adsorbents, the external morphology (surface area and
      mesoporous volume) is the key parameter. The results from thermodynamic analysis
      show, however, that both morphological and chemical properties of both adsorbates
      and adsorbents influenced their behavior.

PMID- 24907713
TI  - Tooth brushing frequency in Mexican schoolchildren and associated socio
      demographic, socioeconomic, and dental variables.
AB  - BACKGROUND: Tooth brushing (with fluoridated toothpaste) is the most cost
      effective intervention in dentistry and it is widely recommended to preserve good
      oral health. We aimed to determine the frequency of tooth brushing and the
      variables associated with this practice in schoolchildren living in southeast
      Mexico. MATERIAL AND METHODS: A cross-sectional study was carried out in 1644
      schoolchildren, 6 to 13 years old. Questionnaires with socio-demographic,
      socioeconomic, and dental variables were administered to mothers/guardians of
      children. The dependent variable was the frequency of tooth brushing, which was
      categorized as 0 = tooth brushing less than once a day and 1 = tooth brushing at
      least once a day. A logistic regression model was used to evaluate the final
      results. RESULTS: Mean age was 9.06+/-2.02 years and 49.1% were girls. The
      prevalence of tooth brushing at least once a day was 49.8%. In the multivariate
      model, characteristics related to tooth brushing frequency (p<0.05) were: older
      age (OR=1.11), being female (OR=1.64), having a larger family (OR=0.87), having
      had a visit to a dentist during the year preceding the study (OR=1.37), and
      having had fluoride applications by a professional (OR=1.39). CONCLUSIONS: The
      results suggested that different variables (demographic, socioeconomic and
      dental) are associated with the frequency of tooth brushing. Family size (proxy
      variable for socioeconomic status) may indicate certain oral health inequalities
      in this population.

PMID- 24907715
TI  - Liver retransplant for primary disease recurrence.
AB  - Liver retransplant is the only treatment for patients with irreversible graft
      failure. However, given the severe shortage of organs, there is an ethical
      question of equity in the distribution of this resource. Liver retransplant is
      more expensive and is associated with lower patient/graft survival rates than
      equivalent rates after primary transplant. Both primary nonfunction and hepatic
      artery thrombosis account for nearly all cases of early liver retransplant. Late
      indications of liver retransplant include chronic rejection, biliary
      complications, or recurrence of primary disease such as hepatitis C, autoimmune
      hepatitis, and primary sclerosing cholangitis. Donor data are not available when
      a patient is listed for liver retransplant; therefore, prognostic factors related
      to the recipient is a more practical way of making the decision to offer liver
      retransplant is made. In the Model of End-stage Liver Disease era liver
      retransplant for "late" indications is more complex and selection criteria are
      more stringent. We review the literature for predictive factors influencing
      outcome of liver retransplant, especially in those with recurrent disease. 

PMID- 24907716
TI  - Efficacy and safety of phosphodiesterase-5 inhibitors for treating erectile
      dysfunction in kidney transplant recipients: a meta-analysis.
AB  - OBJECTIVES: Erectile dysfunction is common after kidney transplant. The
      phosphodiesterase-5 inhibitors are the primary drugs for the treatment of
      erectile dysfunction. The purpose of this study was to evaluate the efficacy and
      safety of these drugs in the treatment of erectile dysfunction after kidney
      transplant. MATERIALS AND METHODS: Randomized controlled trials were identified
      and extracted from MEDLINE, the Web of Science, Cochrane Central, and reference
      lists. The database search, quality assessment, and data extraction were
      performed independently by 2 reviewers. Eligible studies were randomized
      controlled trials and quasi-randomized controlled trials. Treatment efficacy was
      assessed with the International Index of Erectile Function score. RESULTS: There
      were 3 studies identified that satisfied inclusion criteria. The International
      Index of Erectile Function score for phosphodiesterase-5 inhibitors increased >=
      9 points compared with placebo (mean difference, 11.81; 95% confidence interval:
      9.14-14.48; P < .00001). There were no differences between the phosphodiesterase
      5 inhibitors and placebo in the incidence of adverse events, creatinine levels,
      or concentrations of cyclosporine or tacrolimus. CONCLUSIONS: Phosphodiesterase-5
      inhibitors are effective and safe in treating erectile dysfunction after kidney
      transplant. Phosphodiesterase-5 inhibitors do not cause changes in kidney
      function or immunosuppressive drug concentrations after kidney transplant and may
      be used as the first-line treatment for erectile dysfunction in kidney transplant
      recipients.

PMID- 24907717
TI  - Effect of allopurinol on slowing allograft functional decline in kidney
      transplant recipients.
AB  - OBJECTIVES: Hyperuricemia may be a risk factor for graft loss in kidney
      transplant recipients. The purpose of this study was to evaluate the effects of
      allopurinol in kidney transplant recipients. MATERIALS AND METHODS: A single
      center retrospective case-control study was performed with kidney transplant
      recipients who were treated with allopurinol (54 patients) and a control group
      matched for time of transplant (+/- 3 months) and estimated glomerular filtration
      rate (54 patients). We evaluated the relation between allopurinol use and
      estimated glomerular filtration rate, graft survival, blood pressure, and number
      of anti-hypertensive drugs used. RESULTS: At the start of allopurinol therapy,
      mean serum uric acid level was greater in the allopurinol (476 +/- 119 MUmol/L)
      than control group (404 +/- 125 MUmol/L; P <= .001) and estimated glomerular
      filtration rate was similar between the 2 groups (allopurinol, 39 +/- 16 mL/min;
      control, 38 +/- 16 mL/min; not significant). At 1 year, mean estimated glomerular
      filtration rate was greater in the allopurinol than control group (allopurinol,
      41 +/- 15 mL/min; control, 36 +/- 13 mL/min; P <= .04). At 2 years, mean serum
      uric acid level was significantly lower in the allopurinol (399 +/- 101 MUmol/L)
      than control group (452 +/- 95 MUmol/L; P <= .02). Graft survival, blood
      pressure, and antihypertensive requirements were similar between the groups.
      CONCLUSIONS: Allopurinol use is associated with preservation of estimated
      glomerular filtration rate in kidney transplant recipients. There may be
      potential benefit in treating asymptomatic hyperuricemia in kidney transplant
      recipients.

PMID- 24907719
TI  - Minimally invasive procedures for treatment of urolithiasis in transplanted
      kidneys.
AB  - OBJECTIVES: To assess the safety and efficacy of minimally invasive procedures
      for urolithiasis in transplanted kidneys. MATERIALS AND METHODS: A retrospective
      study was done on kidney transplant patients who had urolithiasis treated with
      minimally invasive procedures between January 1989 and September 2011. We
      evaluated patient characteristics, predisposing factors, clinical presentation,
      minimally invasive procedures used, frequency of success, and complications.
      RESULTS: In 1800 kidney transplants, 21 recipients developed urolithiasis (mean
      age, 31 y; 13 men and 8 women) and were treated with minimally invasive
      procedures. Predisposing factors included hyperparathyroidism (6 patients),
      hyperuricemia (5 patients), recurrent urinary tract infection (4 patients),
      ureteral stricture or obstruction (2 patients), and unknown factors (4 patients).
      Clinical presentation included hematuria (5 patients), azotemia (4 patients),
      anuria (3 patients), urinary tract infection (3 patients), and hydronephrosis (2
      patients). The stones were located in the kidney (11 patients) or ureter (10
      patients). Mean stone size was 11 +/- 3 mm (range, 6-18 mm). Depending on the
      size and location of stones, treatment included extracorporeal shock wave
      lithotripsy in 10 patients, transurethral lithotripsy in 9 patients, and
      percutaneous nephrolithotomy in 2 patients. Stone-free status was achieved in 7
      of 10 patients who were treated with shock wave lithotripsy (70%), 8 of 9
      patients who were treated with transurethral lithotripsy (89%), and 2 of 2
      patients who were treated with percutaneous nephrolithotomy (100%). All 4
      patients who did not become stone-free after initial treatment (3 patients after
      shock wave lithotripsy and 1 patient after transurethral lithotripsy) became
      stone-free after secondary treatment with percutaneous nephrolithotomy (100%). No
      intraoperative complications occurred. CONCLUSIONS: Minimally invasive procedures
      (mono-therapy or combination therapy) for urolithiasis in transplanted kidneys
      are safe and effective, and high overall stone-free results may be achieved.

PMID- 24907718
TI  - Immune monitoring with a lymphocyte adenosine triphosphate assay in kidney
      transplant recipients treated with a calcineurin inhibitor.
AB  - OBJECTIVES: The adenosine triphosphate assay using peripheral lymphocytes may be
      useful to evaluate the risks of acute rejection and infection in kidney
      transplant patients. We used the adenosine triphosphate assay to evaluate
      differences between recipients who were treated with cyclosporine- or tacrolimus
      based immunosuppressive therapy. MATERIALS AND METHODS: Adenosine triphosphate
      levels were measured in peripheral CD4+ cells before and after transplant and
      were correlated with clinical outcomes in 45 kidney transplant recipients. These
      recipients received immunosuppressive therapy with either cyclosporine (23
      patients) or tacrolimus (22 patients). RESULTS: Adenosine triphosphate levels
      were significantly lower in the cyclosporine- than tacrolimus-based therapy
      groups from 2 to 6 weeks after transplant. Adenosine triphosphate levels were
      similar between these groups before and 1 week after transplant. The frequency of
      cytomegalovirus infection was greater in the recipients who received cyclosporine
      (17 patients [74%]) than tacrolimus (6 patients [27%]; P ? .003). The frequency
      of acute rejection episodes was similar between the cyclosporine and tacrolimus
      groups. CONCLUSIONS: These observations suggest that cyclosporine-based
      immunosuppressive therapy causes excessive immunosuppression compared with
      tacrolimus-based therapy, evidenced by the lymphocyte adenosine triphosphate
      levels. The adenosine triphosphate assay using peripheral CD4+ cells may be a
      useful method for predicting the occurrence of cytomegalovirus infections in
      kidney transplant recipients.

PMID- 24907720
TI  - Pneumonia after kidney transplant: incidence, risk factors, and mortality.
AB  - OBJECTIVES: Pneumonia is an important cause of morbidity and mortality in
      recipients of solid-organ transplant. We aimed to determine risk factors for
      development of pneumonia and associated deaths in kidney transplant recipients.
      MATERIALS AND METHODS: A retrospective review of medical records was performed
      for all kidney transplant recipients from December 1988, to April 2011. The
      diagnosis of community-acquired pneumonia was made from symptoms, clinical
      findings, and chest radiography. The diagnosis of nosocomial pneumonia was made
      according to published criteria. Laboratory and serologic tests, radiographic
      findings, cultures of respiratory specimens, and tissue biopsies were reviewed.
      RESULTS: In 406 kidney transplant recipients, there were 82 patients (20%) who
      had 111 episodes of pneumonia, including 49 nosocomial episodes of pneumonia
      (44%). Bacterial infections were the most common cause (34 episodes [31%]). In
      multivariate analysis, significant risk factors associated with pneumonia
      episodes were older age, hypertension, cardiac disease, history of acute graft
      rejection, and not using everolimus/mycophenolate mofetil/prednisolone protocol.
      There were 28 episodes that resulted in death (25%), including 20 nosocomial
      episodes (71%). In multivariate analysis, significant risk factors associated
      with death from pneumonia episodes were antibiotic use in the previous 3 months,
      high C-reactive protein, and low albumin. Cutoff values for increased risk of
      death from pneumonia included C-reactive protein > 10 mg/dL and procalcitonin >
      8.8 ng/mL. CONCLUSIONS: Recipients of kidney transplant may be at risk for
      pneumonia and associated death. Nosocomial pulmonary infections may be associated
      with marked morbidity and mortality in kidney transplant recipients.

PMID- 24907721
TI  - Prospective monitoring of cytomegalovirus, Epstein-Barr virus, BK virus, and JC
      virus infections on belatacept therapy after a kidney transplant.
AB  - OBJECTIVES: Few data regarding viral replication in patients receiving belatacept
      are available. The aim of this single-center study was to compare the incidence
      of viral infections (cytomegalovirus, Epstein Barr virus, BK virus, and JC
      virus), in 62 de novo kidney transplant patients enrolled in the BENEFIT studies,
      receiving either belatacept (n=42) or cyclosporine (n=20). MATERIALS AND METHODS:
      By means of polymerase chain reaction, belatacept-treated patients were tested
      for cytomegalovirus, Epstein-Barr virus, BK virus, and JC virus infections
      monthly for 36 months, monthly for the first 6 months, and then quarterly for 36
      months in cyclosporine-treated patients. Additional samples were obtained when a
      viral infection was suspected. RESULTS: The number of positive cytomegalovirus,
      BK virus, or JC virus viremias over the number of polymerase chain reactions
      performed through all 3 years was similar in both groups. Conversely, over the 3
      year study, the number of positive Epstein-Barr virus viremias over the number of
      Epstein-Barr virus polymerase chain reactions performed was significantly higher
      in the belatacept group (76% vs 50%; P = .047). The number of Epstein-Barr virus
      primary infection was similar in both groups, while the number of Epstein-Barr
      virus reactivation was higher in the belatacept group. CONCLUSIONS: Epstein-Barr
      virus replication occurs more often in patients receiving belatacept, than it
      does in those receiving cyclosporine.

PMID- 24907722
TI  - Long-acting erythropoietin stimulating agents for persistent anemia after kidney
      transplant: risk factors and outcome.
AB  - OBJECTIVES: Posttransplant anemia is associated with an increased risk of
      congestive heart failure, left ventricular hypertrophy, and death. The purpose of
      this study was to evaluate the effect of long-acting erythropoietin-stimulating
      agents on anemia after kidney transplant. MATERIALS AND METHODS: In 2306 kidney
      transplant recipients, 250 anemic patients (11%) with stable graft function were
      followed at the Hamed Al-Essa Organ Transplant Centre (Kuwait) and were assessed
      for anemia. We enrolled 120 patients into this open-label study in 2 groups:
      group 1 had treatment with darbepoetin alfa (86 patients) and group 2 had
      continuous erythropoietin receptor activator (34 patients). RESULTS: Patient age
      correlated negatively with serum iron level. Serum ferritin correlated negatively
      with hemoglobin level 6 months after transplant but not at time of transplant.
      Most patients were women who received their grafts from male donors. The 2 groups
      were comparable in frequency of rejection and mean hemoglobin and serum albumin
      levels at 3, 6, 9, and 12 months after transplant. There was no difference
      between the 2 groups in renal function (estimated glomerular filtration rate);
      posttransplant complications such as new-onset diabetes after transplant,
      hypertension, serious bacterial infections, or patient and graft outcomes.
      CONCLUSIONS: Anemia is an important problem after kidney transplant, and iron use
      is suboptimal in kidney transplant recipients. Darbepoetin alfa and continuous
      erythropoietin receptor activator had comparable positive results.

PMID- 24907723
TI  - Living-donor kidney transplant in T-cell and B-cell flow cytometry crossmatch
      positive patients.
AB  - OBJECTIVES: Complement-dependent cytotoxic crossmatch is an important indicator
      for kidney transplant. However, there is controversy about treatment for flow
      cytometry crossmatch-positive cases. MATERIALS AND METHODS: This was a
      retrospective study of 127 living-donor kidney transplant recipients from May
      2007 to July 2011. We divided patients into 115 flow cytometry crossmatch T-cell
      and B-cell-negative cases, and 12 T-cell and B-cell-positive cases. Both groups
      were given 20 mg basiliximab the day of surgery and 4 days after surgery. Common
      oral immunosuppressive agents used were tacrolimus, mycophenolate mofetil, and
      methylprednisolone. Flow cytometry crossmatch T-cell and B-cell-negative
      recipients started immunosuppression 7 days before surgery, T-cell and B-cell
      positive recipients started immunosuppression 14 days before surgery. T-cell and
      B-cell-positive patients also received 200 mg rituximab 1 week before surgery,
      had 3 plasma exchange sessions before transplant, and received intravenous
      immunoglobulin 20 g/day during surgery and after surgery for 5 days. We measured
      flow-panel reactive antibodies of T-cell and B-cell-positive patients just before
      surgery to check desensitization efficiency. We evaluated patient survival, graft
      survival, graft function, and frequency of rejection and infectious diseases.
      RESULTS: Patient survival and graft survival were 100% in both groups. Flow
      cytometry crossmatch T-cell and B-cell-positive cases had no rejection events,
      but T-cell and B-cell-negative groups developed rejection. There was no
      statistical difference in the incidence of infection and graft function. Flow
      panel reactive antibody demonstrated improvement in all T-cell and B-cell
      positive cases. CONCLUSIONS: In living-donor kidney transplant, flow cytometry
      crossmatch T-cell and B-cell-positive patients are still considered to be at high
      risk. Although this is a short-term outcome, all T-cell and B-cell-positive
      patients in this study achieved excellent results with appropriate preoperative
      and postoperative treatment.

PMID- 24907724
TI  - Nonmelanoma skin cancer after kidney transplant.
AB  - OBJECTIVES: Solid-organ transplant recipients have a high risk of developing
      nonmelanoma skin cancers. This study sought to determine the incidence of skin
      cancer and identify possible risk factors for skin cancer in kidney transplant
      recipients. MATERIALS AND METHODS: Nonmelanoma skin cancer was diagnosed and
      confirmed with histology in 33 of 1275 kidney transplant recipients (2.6%).
      Demographic and clinical findings were reviewed retrospectively. RESULTS:
      Nonmelanoma skin cancers included squamous cell carcinoma in 10 patients (30%),
      basal cell carcinoma in 9 patients (27%), Kaposi sarcoma in 9 patients (27%),
      squamous cell carcinoma in situ in 3 patients (9%), and cutaneous lymphoma in 2
      patients (6%). The ratio of squamous cell carcinoma to basal cell carcinoma was
      1.1:1. The mean time from transplant to skin cancer diagnosis was 65 +/- 55
      months (range, 0-180 mo). Immunosuppressive therapy was based on cyclosporine in
      22 patients (67%), tacrolimus in 8 patients (24%), and combination therapy
      (cyclosporine and azathioprine) in 3 patients (9%). CONCLUSIONS: Nonmelanoma skin
      cancer is an important clinical problem in kidney transplant recipients.
      Interventions that may benefit kidney transplant recipients may include intensive
      patient education, protection against sun exposure, and dermatologic screening
      programs.

PMID- 24907726
TI  - Venous outflow reconstruction using an expanded polytetrafluoroethylene vascular
      graft in living-donor liver transplant: a single-center experience.
AB  - OBJECTIVES: Limited studies have focused on the feasibility and technical
      requirements of using expanded polytetrafluoroethylene vessel grafts for venous
      outflow reconstruction in a living-donor liver transplant using right liver
      grafts without the middle hepatic vein. MATERIALS AND METHODS: Between August
      2007 and December 2012, thirty-two patients who had received an expanded
      polytetrafluoroethylene vascular graft for outflow reconstruction during a living
      donor liver transplant using a right liver graft without the middle hepatic vein
      were retrospectively reviewed. Preoperative and operative data, complications,
      and mortality were compared among patients who received the expanded
      polytetrafluoroethylene grafts with individual anastomoses (n = 18) or confluent
      anastomoses (n =14). RESULTS: For patients who had received an individual and a
      confluent anastomosis, graft reconstruction time was 25.8 and 14.9 minutes (P =
      .000). No cases of graft occlusion occurred during first 72 hours after surgery.
      Although 5 patients (15.6%) died within 90 days, none of the deaths were
      associated with the vascular grafts. Operative mortality was not statistically
      different between patients who had received an individual anastomosis (3/18,
      16.7%) and those who had received a confluent anastomosis (2/14, 14.3%) (P =
      1.000). CONCLUSIONS: Individual and confluent anastomoses using an expanded
      polytetrafluoroethylene vascular graft is a feasible approach to venous outflow
      reconstruction in a living-donor liver transplant using right liver grafts
      without the middle hepatic vein.

PMID- 24907725
TI  - Portal vein thrombosis before liver transplant does not alter postoperative
      patient or graft survival.
AB  - OBJECTIVES: Portal vein thrombosis may complicate liver transplant. The purpose
      of this study was to analyze our cohort of transplanted recipients to evaluate
      the relation between preoperative portal vein thrombosis and patient and graft
      survival after liver transplant. MATERIALS AND METHODS: We retrospectively
      analyzed 209 patients who had liver transplant; 2 patients who had the diagnosis
      of portal vein thrombosis made during surgery were excluded. Patients were
      stratified in 2 groups according to whether they had (15 patients) or did not
      have portal vein thrombosis (192 patients) before liver transplant and were
      compared for early and late survival. RESULTS: In all 15 patients who had portal
      vein thrombosis, the Yerdel grade was I or II. Patients who had preoperative
      portal vein thrombosis had lower median survival (portal vein thrombosis, 47 mo;
      no portal vein thrombosis, 61 mo), frequency of total number of deaths (portal
      vein thrombosis, 4 [27%]; no portal vein thrombosis, 68 [35%]), and frequency of
      death within 3 months after transplant (portal vein thrombosis, 1 [7%]; no portal
      vein thrombosis, 23 [12%]). However, there was no significant difference between
      the 2 groups in patient or graft survival. CONCLUSIONS: Low-grade portal vein
      thrombosis detected before liver transplant is not an absolute contraindication
      for liver transplant. Radiographic screening before liver transplant is
      recommended to minimize surgical difficulty.

PMID- 24907727
TI  - Protective effects of osthole on intestinal ischemia-reperfusion injury in mice.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of intravenous
      injection of osthole on intestinal ischemia-reperfusion injury and parameters of
      oxidative stress. MATERIALS AND METHODS: In 45 Kunming male mice, treatment
      included sham surgery (15 mice); intestinal ischemia-reperfusion injury (clamping
      of the superior mesenteric artery, 2 h; clamp release, 1 h; 15 mice); or osthole
      treatment before and after ischemia-reperfusion injury (15 mice). Evaluation
      included histopathology, determination of intestinal wet/dry weight ratio, and
      measurement of levels of diamine oxidase, superoxide dismutase, malondialdehyde,
      interleukin 1beta, tumor necrosis factor alpha, and interleukin 2. Intestinal
      barrier permeability was evaluated with Evans blue test. RESULTS: The mean wet-to
      dry weight ratio, Evans blue content, and Chiu score were significantly greater
      in the ischemia-reperfusion than in the sham group and lower in the osthole
      treated than the ischemia-reperfusion group. The mean serum diamine oxidase,
      malondialdehyde, interleukin 1beta, and tumor necrosis factor alpha levels were
      significantly greater in the ischemia-reperfusion than in the sham group and
      lower in the osthole-treated than in the ischemia-reperfusion group. The mean
      superoxide dismutase activity and interleukin 2 levels were lower in the ischemia
      reperfusion than in the sham group and greater in the osthole-treated than in the
      ischemia-reperfusion group. CONCLUSIONS: Treatment with osthole may protect
      against oxidative stress and tissue damage from intestinal ischemia-reperfusion
      injury.

PMID- 24907728
TI  - Effects of human amniotic mesenchymal stromal cells on rabbit T-cell responses in
      a xenolymphocyte reaction assay.
AB  - OBJECTIVES: To evaluate the immunomodulatory properties of human amniotic
      mesenchymal stromal cells. MATERIALS AND METHODS: Human amniotic mesenchymal
      stromal cells were isolated, characterized by flow cytometry, cultured in vitro,
      and evaluated in allogeneic and xenogeneic mixed lymphocyte reactions. The
      proliferation of T cells and the expression of interleukin 2 and interferon gamma
      by T cells were evaluated in the presence of human amniotic mesenchymal stromal
      cells. RESULTS: Human amniotic mesenchymal stromal cells were successfully
      isolated from human amniotic membranes and had well-defined human mesenchymal
      stem cell markers (CD90, CD73, CD105, and CD166). The human amniotic mesenchymal
      stromal cells inhibited the proliferation of human and rabbit T cells and the
      secretion of interleukin-2 and interferon gamma by human T cells. CONCLUSIONS:
      Human amniotic mesenchymal stromal cells may be useful for cell therapy and
      tissue engineering because of availability, phenotypic plasticity, and
      immunomodulatory properties.

PMID- 24907729
TI  - Hyperbaric oxygen therapy for hemorrhagic cystitis.

PMID- 24907730
TI  - Preparation and biocompatibility of grafted functional beta-cyclodextrin
      copolymers from the surface of PET films.
AB  - The hydrophobic inert surface of poly(ethylene terephthalate) (PET) film has
      limited its practical bioapplications, in which case, better biocompatibility
      should be achieved by surface modification. In this work, the copolymer of
      functional beta-cyclodextrin derivatives and styrene grafted surfaces was
      prepared via surface-initiated atom transfer radical polymerization (SI-ATRP) on
      initiator-immobilized PET. The structures, composition, properties, and surface
      morphology of the modified PET films were characterized by fourier transform
      infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), contact
      angle measurement, and scanning electronic microscopy (SEM). The results show
      that the surface of PET films was covered by a thick targeted copolymer layer,
      and the hydrophobic surface of PET was changed into an amphiphilic surface. The
      copolymer-grafted surfaces were also shown good biocompatibility on which SGC
      7901 A549 and A549/DDP cells readily attached and proliferated, demonstrating
      that the functional copolymer-grafted PET films could be a promising alternative
      to biomaterials especially for tissue engineering. 

PMID- 24907731
TI  - Preparation of melt-spun antimicrobially modified LDH/polyolefin nanocomposite
      fibers.
AB  - Layered double hydroxide (LDH) was synthesized and organically modified with
      camphorsulfonic acid (CSA) and ciprofloxacin. The thermal stability of CSA was
      improved remarkably under LDH shielding. A minimal inhibitory concentration of
      free CSA against tested bacteria was determined in order to define the essential
      quantity in LDH modification. The modified LDHs were melt-compounded with high
      density polyethylene and the prepared nanocomposites were further melt-spun using
      a piston-type spinning device. The melt-spun fibers were tested for their
      antimicrobial activity against Escherichia coli, Proteus vulgaris, Pseudomonas
      aeruginosa, Enterobacter cloacae, Staphylococcus aureus, Staphylococcus
      epidermidis, and Streptococcus pyogenes. CSA integrated fibers show
      susceptibility against Gram-positive bacteria and ciprofloxacin integrated fibers
      showed activity against both Gram-positive and Gram-negative bacteria. 

PMID- 24907733
TI  - Structural characterisation of oxygen diffusion hardened alpha-tantalum PVD
      coatings on titanium.
AB  - Titanium substrates were coated with tantalum layers of 5 MUm thickness using
      physical vapour deposition (PVD). The tantalum layers showed a (110)-preferred
      orientation. The coated samples were hardened by oxygen diffusion. Using X-ray
      diffraction the crystallographic structure of the tantalum coatings was
      characterised, comparing untreated and diffusion hardened specimen conditions.
      Oxygen depth profiles were determined by glow discharge spectrometry. The
      hardening effect of the heat treatment was examined by Vickers microhardness
      testing. The increase of surface hardness caused by oxygen diffusion was at least
      50%.

PMID- 24907732
TI  - Novel green synthetic strategy to prepare ZnO nanocrystals using rambutan
      (Nephelium lappaceum L.) peel extract and its antibacterial applications.
AB  - In the present investigation, we report a sustainable novel green synthetic
      strategy to synthesis zinc oxide nanocrystals. This is the first report on
      sustainable biosynthesis of zinc oxide nanocrystals employing Nephelium lappaceum
      L., peel extract as a natural ligation agent. Green synthesis of zinc oxide
      nanocrystals was carried out via zinc-ellagate complex formation using rambutan
      peel wastes. The successful formation of zinc oxide nanocrystals was confirmed
      employing standard characterisation studies. A possible mechanism for the
      formation of ZnO nanocrystals with rambutan peel extract was also proposed. The
      prepared ZnO nanocrystals were coated on the cotton fabric and their
      antibacterial activity were analyzed. ZnO nanocrystals coated cotton showed good
      antibacterial activity towards Escherichia coli (E. coli), gram negative bacteria
      and Staphylococcus aureus (S. aureus), gram positive bacteria. 

PMID- 24907734
TI  - New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into
      reduction-sensitive micelles for triggered drug release.
AB  - For the development of biomimetic carriers for stimuli-sensitive delivery of
      anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the
      disulfide bond was prepared for the first time by the ring-opening polymerization
      of benzyl glutamate N-carboxy anhydride in the presence of (propargyl
      carbamate)ethyl dithio ethylamine and then click conjugation with alpha-azido
      dextran. Its structure was characterized by Fourier-transform infrared
      spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic
      nature, such a conjugate could self assemble into nanosize micelles in aqueous
      medium, as confirmed by fluorometry, transmission electron microscopy and dynamic
      light scattering. For the resultant micelles, it was found to encapsulate poorly
      water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of
      45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX
      was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio
      DL-threitol (DTT), analogous to the intracellular redox potential.

PMID- 24907735
TI  - Application of nanoporous silicas as adsorbents for chlorinated aromatic
      compounds. A comparative study.
AB  - The removal of two selected environmental pollutants such as 2,4
      dichlorophenoxyacetic acid (2,4-D) and Triclosan (TC) was examined by adsorption
      experiments on the modified SBA-15 and MCF mesoporous silicas. Mesoporous
      adsorbents were modified by a grafting process with (3
      aminopropyl)triethoxysilane (APTES) and 1-[3-(trimethoxysilyl)propyl]urea
      (TMSPU). Mesoporous materials were synthesized and characterized by N2 adsorption
      desorption experiment, transmission electron microscopy (TEM), Fourier transform
      infrared spectroscopy (FT-IR), elemental analysis and adsorption studies. The
      results show that both APTES-functionalized SBA-15 and MCF nanoporous carriers
      are potentially good adsorbents for the removal of 2,4-D in a wide range of
      concentrations from 0.1 to 4 mg/cm(3). Maximum adsorption capacity of as-modified
      adsorbents for 2,4-D estimated from the Langmuir model was ~280 mg/g. The ionic
      interaction between the adsorbent and 2,4-D seems to play a key role in the
      adsorption process of the pollutant on APTES-modified siliceous matrices. The
      efficiency of TC sorption onto all prepared mesoporous adsorbents was
      significantly lower as compared to the entrapment of 2,4-D. Experimental data
      were best fitted by the Langmuir isotherm model. The results of this study
      suggest that mesoporous silica-based materials are promising adsorbents for the
      removal of selected organic pollutants.

PMID- 24907736
TI  - Galactosylated poly(epsilon-caprolactone) membrane promoted liver-specific
      functions of HepG2 cells in vitro.
AB  - The lack of pendant functional groups on the PCL backbone has been a great
      challenge for surface bioactivation of poly(epsilon-caprolactone) (PCL). In the
      present study, covalently galactosylated PCL (GPCL) was developed through
      coupling between the amino-functionalized PCL (NPCL) and the lactobionic acid
      (LA) and its potential application in maintenance of physiological functions of
      HepG2 cells was further evaluated. The structure and properties of GPCL were
      explored by (1)H NMR, FT-IR, GPC and DSC. Moreover, the incorporation of
      galactose ligands onto GPCL membranes not only promoted higher wettability, but
      also radically changed surface morphology in comparison with PCL and NPCL
      according to the contact angle measurement and atomic force microscopy. When
      HepG2 cells were seeded onto these membranes, the cells on GPCL membranes showed
      more pronounced cell adhesion and tended to form aggregates during the initial
      adhesion stage and then progressively grew into multi-layer structures compared
      to those without galactose ligands by the observation with fluorescence
      microscope and scanning electron microscopy. Furthermore, live-dead assay and
      functional tests demonstrated that HepG2 cells on GPCL membranes had superior
      viability and maintained better liver-specific functions. Collectively, GPCL has
      great potential for hepatic tissue engineering scaffolds. 

PMID- 24907737
TI  - Preparation of keratin hydrogel/hydroxyapatite composite and its evaluation as a
      controlled drug release carrier.
AB  - Infection after artificial joint replacement is a serious problem, which requires
      the re-implantation of prosthesis. To aim at developing bone filling materials
      having both osteoconductivity and ability as a sustained drug release carrier,
      composites of wool keratin or carboxymethylated (CM) keratin hydrogels with
      hydroxyapatite were prepared and evaluated as a sustained drug release carrier.
      CM-keratin was prepared by the reaction of keratin extracted from wool with
      iodoacetic acid. Hydrogels were obtained by dropping keratin or CM-keratin
      solution into CaCl2 solution. The composites were obtained by immersing hydrogels
      in simulated body fluid (SBF). The introduction of carboxymethyl groups to
      keratin facilitated the deposition of hydroxyapatite on hydrogel. After 7 days of
      immersion in SBF, a 4-5 times higher amount of hydroxyapatite was accumulated on
      CM-keratin hydrogel than that on keratin hydrogel. When salicylic acid was loaded
      on keratin and CM-keratin hydrogels, a good sustained release was observed; that
      is, 90% of a drug was released up to 14 days after 60 and 45% of the initial
      burst in 1 day. On the other hand, initial release within 1 day was suppressed by
      forming a composite with hydroxyapatite and the release was almost ceased at 3
      days when 60% of the drug was released. Although further improvement to prolong
      drug release might be necessary, CaKHA and CaCMKHA are expected to be a promising
      novel type of bone filling materials which has both osteoconductivity and
      sustained drug release ability.

PMID- 24907738
TI  - Graphene and carbon nanotube composite enabling a new prospective treatment for
      trichomoniasis disease.
AB  - We report the synthesis and application of novel graphene oxide and carbon
      nanotube oxide (GCN-O) composite. First, pristine multi-walled carbon nanotube
      was prepared by chemical vapour deposition furnace and then exfoliated and
      oxidised simultaneously by oxygen plasma etching. The superficial and volumetric
      compositions of GCN-O were measured by XPS spectroscopy and EDX spectroscopy,
      respectively. Both XPS and EDX analyses evidence that the GCN-O is composed of up
      to 20% of oxygen atoms. As a result, GCN-O forms a stable colloidal aqueous
      solution and shows to have strong interaction with the cell membrane of
      Tritrichomonas foetus protozoa, making easy its application as a drug carrier.
      Trichomoniasis infection of cattle is a devastating disease for cattle producers,
      causing some damages to females and fetus, and the abortion is the most serious
      result of this disease. There is no effective treatment for trichomoniasis
      infection yet. Therefore, new treatment, especially one with no collateral
      effects in animals, is required. With this goal in mind, our results suggest that
      water dispersible composite is a novel nanomaterial, promising for Trichomoniasis
      infection treatment and as therapeutic delivery agent as well. 

PMID- 24907739
TI  - Antibacterial performance of ZnO-based fillers with mesoscale structured
      morphology in model medical PVC composites.
AB  - Three different ZnO-based antibacterial fillers having different morphologies in
      microscale region were prepared by the use of the microwave assisted synthesis
      protocol created in our laboratory with additional annealing in one case.
      Further, PVC composites containing 0.5-5 wt.% of ZnO based antibacterial fillers
      were prepared by melt mixing and characterized by scanning electron microscopy
      (SEM) and X-ray diffractometry (XRD). Mechanical testing showed no adverse effect
      on the working of polymer composites due to either of the fillers used or the
      applied processing conditions in comparison with the neat medical grade PVC. The
      surface antibacterial activity of the compounded PVC composites was assessed
      against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538P according
      to ISO 22196: 2007 (E). All materials at almost all filler loading levels were
      efficient against both species of bacteria. The material with the most expanding
      morphology assuring the largest contact between filler and matrix achieved an
      excellent level of more than 99.9999% reduction of viable cells of E. coli in
      comparison to untreated PVC and performed very well against S. aureus, too. A
      correlation between the morphology and efficacy of the filler was observed and,
      as a result, a general rule was formulated which links the proneness of the
      microparticles to perform well against bacteria to their shape and morphology.

PMID- 24907740
TI  - Comparative study of thermal stability of magnetostrictive biosensor between two
      kinds of biorecognition elements.
AB  - Magnetostrictive biosensors specific to Salmonella typhimurium were prepared by
      immobilizing antibody or phage as biorecognition elements onto the
      magnetostrictive sensor platform. The sensors were stored at temperatures of 25 
      degrees C (room temperature), 45  degrees C and 65  degrees C, respectively, and
      the ability to bind S. typhimurium was detected by testing the resonant frequency
      shift using a HP network analyzer after exposure to 1 mL of 1*10(9) cfu/mL of S.
      typhimurium at a predetermined schedule. The binding of S. typhimurium to
      biosensors was confirmed by Scanning Electron Microscopy (SEM). The results
      showed that there existed an initial sudden drop in the average density of S.
      typhimurium bound to the biosensor surface versus duration at different
      temperatures for the two kinds of recognition elements, and the binding ability
      to S. typhimurium of phage-immobilized biosensors was much better than that of
      antibody-immobilized biosensors, with longevity longer than 30 days at all tested
      temperatures, though decreasing gradually over the testing period. While the
      longevity of antibody-immobilized biosensors was only about 30, 8 and 5 days at
      room temperature (25  degrees C), 45  degrees C and 65  degrees C, respectively.
      Meanwhile, the activation energy of the two kinds of biosensors was investigated,
      and it was found that phage immobilized sensors showed much higher activation
      energy than antibody immobilized sensors, which resulted in less dependency on
      temperature and thus having much better thermal stability than antibody
      immobilized sensors.

PMID- 24907741
TI  - On the deformation behavior of human dentin under compression and bending.
AB  - The cause of difference in deformation behavior of human dentin under compression
      and bending is discussed. Mechanical properties of dentin under these deformation
      schemes are compared. Microstructural study of fracture surfaces of samples and
      cracks in dentin is carried out, too. Dentin behaves like a brittle solid under
      bending, whereas it exhibits various types of response from brittle to highly
      deformable under compression that depended on the geometry of sample (d/h ratio
      of a cubic sample). It is shown that the quantity of cracks on the compressed
      sample increases when its elasticity and plasticity grow up, whereas under
      bending the failure of sample occurs due to the advancement of dominant crack.
      Deformation and crack growth are the channels for the accommodation of applied
      stress in dentin. Crack growth is the leading one when the level of tensile
      stress in sample is dominant, whereas deformation becomes the leading channel
      when compression stress is dominant. However, in both cases contribution of the
      concurrent channel cannot be ignored. This feature is caused by the ductile
      fracture mode of dentin on the mesoscopic level. 

PMID- 24907742
TI  - Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor
      water soluble drugs: ibuprofen.
AB  - Current methods for preparation of PEGylated chitosan have limitations such as
      harsh de protecting step and several purification cycles. In the present study, a
      facile new method for conjugating methoxy polyethylene glycol (mPEG) to chitosan
      under mild condition is introduced to improve water solubility of chitosan and
      control the release of poor water soluble drugs. The method consists of chitosan
      modification by grafting the C6 position of chitosan to mPEG which is confirmed
      by Fourier transformed-infrared (FT-IR) and proton nuclear magnetic resonance
      ((1)HNMR) analyses. The amine groups at the C2 position of chitosan are protected
      using sodium dodecylsulfate (SDS) which is removed by dialyzing the precipitation
      against Tris solution. The chemical structure of the prepared polymer is
      characterized by FTIR and (1)HNMR. The synthesized polymer is then employed to
      prepare nanoparticles which are characterized by transmission electron microscopy
      (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), and
      dynamic light scattering (DLS) for their size and morphology. The nanoparticles
      are used for encapsulation of ibuprofen followed by in vitro release
      investigation in gastrointestinal and simulated biological fluids. The chitosan
      nanoparticles are used as control. The PEGylated nanoparticles show a particle
      size of 80 nm with spherical morphology. The results clearly show that drug
      release from PEGylated chitosan nanoparticles is remarkably slower than chitosan.
      In addition, drug encapsulation and encapsulation efficiency in PEGylated
      nanoparticles are dependent on the amount of drug added to the formulation being
      significantly higher than chitosan nanoparticles. This study provides an
      efficient, novel, and facile method for preparing a nano carrier system for
      delivery of water insoluble drugs.

PMID- 24907743
TI  - A review of recent advances in nonenzymatic glucose sensors.
AB  - Currently, there is an overwhelming demand for the development and improvement of
      glucose sensors. Not only has the number of people requiring these sensors
      significantly increased over the last decade, so has the demand to make sensors
      which are both biocompatible and have increased sensing capabilities as compared
      to current technologies. In order to meet these needs, a move towards
      nonenzymatic glucose sensors has begun. These new sensors have garnered
      significant interest due to their capacity to achieve continuous glucose
      monitoring, their high stability compared to traditional glucose sensors, and the
      ease of their fabrication. Research has been extensively geared towards the
      preparation of these nonenzymatic glucose sensors from novel materials, often
      with unique micro- or nano-structures, which possess ideal properties for
      electrochemical biosensor applications. In recent years, a variety of materials
      including noble metals, metal oxides, carbon nanotubes, graphene, polymers, and
      composites have been explored for their electrocatalytic response to the
      oxidation of glucose. In this review, the most recent advances in nonenzymatic
      glucose sensors are visited, with the focus being on the last five years of
      research. 

PMID- 24907745
TI  - Modeling in vivo corrosion of AZ31 as temporary biodegradable implants.
      Experimental validation in rats.
AB  - In this paper, two complementary approaches, mathematical modeling and
      experimental results are combined to identify variables that affect the in vivo
      biodegradation of magnesium implants. The in vivo corrosion behavior of AZ31
      alloy proposed for temporary applications as fixation of bone fractures has been
      modeled solving the Laplace equation by finite element method (FEM). Bar-shaped
      AZ31 implants of 1mm diameter and 20mm length were inserted in Wistar rat femurs
      with and without a fracture. The presence of gas around AZ31 implants inside the
      femurs has been detected in situ at the epiphysis and in fractured areas by
      computerized tomography (CT). Examining some in vivo conditions, the model
      confirms that magnesium-alloy devices have different biodegradation behavior,
      depending on the thickness of electrolyte at the implantation site and can be
      used for predicting the biodegradation behavior. 

PMID- 24907744
TI  - Poly(L-lactide) and poly(butylene succinate) immiscible blends: from
      electrospinning to biologically active materials.
AB  - For the first time the preparation of defect-free fibers from immiscible blends
      of high molar mass poly(lactic acid) (PLA) and poly(butylene succinate) (PBS) in
      the whole range of the polyester weight ratios is shown. Electrospinning using
      the solvent-nonsolvent approach proved most appropriate. Moreover,
      electrospinning revealed crucial for the obtaining of PLA/PBS materials
      maintaining integrity. DSC and XRD analyses attested for a plasticizing effect
      and for increased PLA crystallinity at PBS addition to PLA. The mechanical
      properties of the PLA/PBS mats were controlled by the alignment of the fibers and
      changed from plastic to brittle materials upon increasing the PBS content. Drug
      loading and tests against pathogenic microorganisms suggested that the obtained
      mats can find application as antibacterial fibrous materials.

PMID- 24907746
TI  - A nano-silver composite based on the ion-exchange response for the intelligent
      antibacterial applications.
AB  - As a kind of antimicrobial agent, nano-silver composites have attracted a great
      deal of interest in biomedical applications. However, the typical loadings of
      silver nanoparticles (AgNPs) in such composites could result in dose-related
      cytotoxicity. In this study, a nano-silver composite leading to antimicrobial
      activity without cytotoxicity was fabricated by loading AgNPs into a dried
      alginate hydrogel. The biological performance of this composite mainly depended
      on the release of AgNPs, which needed to be triggered by the ion-exchange
      response and was further influenced by the loadings of AgNPs in the composite.
      The antimicrobial activity against E. coli and S. aureus demonstrated that the
      released silver no less than 678 ppb in the medium caused a reduction of
      7log10CFU/mL (100%) bacteria. Significantly, the dose (~1.10*10(3) ppb) of
      released silver was not toxic and allowed attachment, and growth of MC3T3-E1 pre
      osteoblast cells. These results supported that the composite was compatible with
      in vitro mammalian cells yet exhibited antimicrobial activity by carefully
      designing the loadings of AgNPs within the alginate. Thus, it indicated that the
      performance of this composite might permit management of bacterial infection in
      wound beds without impairment of wound healing.

PMID- 24907748
TI  - Osteogenic differentiation and mineralization of human exfoliated deciduous teeth
      stem cells on modified chitosan scaffold.
AB  - Stem cells from human exfoliated deciduous teeth (SHEDs) have been considered as
      alternative sources of adult stem cells in tissue engineering because of their
      potential to differentiate into multiple cell lineages. Strontium has an
      important function in bone remodeling because it can simulate bone formation and
      decrease bone resorption. In this study, the effects of strontium phosphate on
      the osteogenic differentiation of SHEDs were investigated. Strontium phosphate
      was found to enhance the osteogenic differentiation of SHEDs with up-regulated
      osteoblast-related gene expression. The proliferation of SHEDs was slightly
      inhibited by chitosan scaffolds; however, type-I collagen expression, alkaline
      phosphatase activity, and calcium deposition on chitosan scaffolds containing
      strontium were significantly enhanced. Furthermore, cells seeded in a 3D scaffold
      under dynamic culture at an optimal fluid rate might enhance cellular
      differentiation than static culture in osteoblastic gene expression. This
      experiment might provide a useful cell resource and dynamic 3D culture for tissue
      engineering and bone repair. 

PMID- 24907747
TI  - Glucose-sensitive colorimetric sensor based on peroxidase mimics activity of
      porphyrin-Fe3O4 nanocomposites.
AB  - 5,10,15,20-Tetrakis(4-carboxyphenyl)-porphyrin-functionalized Fe3O4
      nanocomposites (H2TCPP-Fe3O4) were successfully prepared by a simple two-step
      method. These nanocomposites exhibited ultra-high peroxidase-like activity
      compared with pure Fe3O4 nanoparticles. Colorless peroxidase substrate 3,3,5,5
      tetramethylbenzidine (TMB) was changed by H2O2 to its blue oxidized state.
      Kinetic studies indicated that the H2TCPP-Fe3O4 nanocomposites exhibited enhanced
      affinity toward H2O2 with a higher catalytic activity than Fe3O4 nanoparticles
      alone. Results of a fluorescent probe suggested that the catalase-mimic activity
      of the H2TCPP-Fe3O4 nanocomposites effectively catalyzed the decomposition of
      H2O2 into hydroxyl radicals. A simple, sensitive, and selective visual and
      colorimetric method with TMB as the substrate was designed to detect glucose when
      combined with glucose oxidase. This colorimetric method can be used for
      colorimetric detection of H2O2 with a minimum detection limit of 1.07*10(-6) M
      and a dynamic range of 5*10(-6) mol.L(-1) to 8*10(-5) mol.L(-1). This method can
      also be used to detect glucose at a minimum detection limit of 2.21*10(-6) M and
      a dynamic range of 25*10(-6) mol.L(-1) to 5*10(-6) mol.L(-1). Furthermore, the
      robustness of the nanocomposites makes them suitable for a wide range of
      applications in biomedicine and environmental chemistry fields.

PMID- 24907749
TI  - One-pot facile synthesis of PEGylated superparamagnetic iron oxide nanoparticles
      for MRI contrast enhancement.
AB  - Polyethylene glycol (PEG)-coated superparamagnetic iron oxide nanoparticles
      (PEG.SPIONs) were prepared by a facile one-pot approach. The synthesized
      PEG.SPIONs were found to be uniform in size with an average hydrodynamic diameter
      of 11.7 nm. PEG.SPIONs exhibited excellent dispersibility in water, colloidal
      stability, and biocompatibility. The magnetic resonance imaging (MRI) properties
      of PEG.SPIONs were characterized both in vitro and in vivo. The dual contrast
      both in T1 and T2-weighted imaging was well enhanced with longitudinal and
      transverse relaxivity (r1, r2) of 35.92 s(-1) per mM of Fe(3+) and 206.91 s(-1)
      per mM of Fe(3+) respectively. In vivo T2-weighted MRI shows pronounced
      enhancement in the liver and spleen but not in T1-weighted MRI. Accumulations of
      nanoparticles were found primarily in the liver, spleen, and intestine, while
      much lower uptake in the kidney, heart, and lungs. A gradual excretion of
      PEG.SPIONs was observed via hepatobiliary (HB) processing over a period of 14
      days. The toxicity of PEG.SPIONs was also evaluated in vitro and in vivo.
      PEG.SPIONs were found to be biocompatible by investigating organ tissues after
      hematoxylin-eosin staining. The conclusion of the study indicates a high
      potential of PEG.SPIONs in medical MRI.

PMID- 24907750
TI  - In vitro study of nanostructured diopside coating on Mg alloy orthopedic
      implants.
AB  - The high corrosion rate of Mg alloys has hindered their application in various
      areas, particularly for orthopedic applications. In order to decrease the
      corrosion rate and to improve the bioactivity, mechanical stability and
      cytocompatibility of the Mg alloy, nanostructured diopside (CaMgSi2O6) has been
      coated on AZ91 Mg alloy using a combined micro arc oxidation (MAO) and
      electrophoretic deposition (EPD) method. The crystalline structure, the
      morphology and the composition of the samples were characterized by X-ray
      diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform
      infrared spectroscopy (FTIR). Electrochemical corrosion test, immersion test, and
      compression test were used to evaluate the corrosion resistance, the in vitro
      bioactivity and the mechanical stability of the samples, respectively. The
      cytocompatibility of the samples was tested by the cell viability and the cell
      attachment of L-929 cells. The results confirmed that the diopside coating not
      only slows down the corrosion rate, but also enhances the in vitro bioactivity,
      mechanical stability and cytocompatibility of AZ91 Mg alloy. Therefore, Mg alloy
      coated with nanostructured diopside offers a promising approach for biodegradable
      bone implants. 

PMID- 24907751
TI  - Drug delivery vehicles on a nano-engineering perspective.
AB  - Nanoengineered drug delivery systems (nDDS) have been successfully used as
      clinical tools for not only modulation of pharmacological drug release profile
      but also specific targeting of diseased tissues. Until now, encapsulation of anti
      cancer molecules such as paclitaxel, vincristin and doxorubicin has been the main
      target of nDDS, whereby liposomes and polymer-drug conjugates remained as the
      most popular group of nDDS used for this purpose. The success reached by these
      nanocarriers can be imitated by careful selection and optimization of the
      different factors that affect drug release profile (i.e. type of biomaterial,
      size, system architecture, and biodegradability mechanisms) along with the
      selection of an appropriate manufacture technique that does not compromise the
      desired release profile, while it also offers possibilities to scale up for
      future industrialization. This review focuses from an engineering perspective on
      the different parameters that should be considered before and during the design
      of new nDDS, and the different manufacturing techniques available, in such a way
      to ensure success in clinical application. 

PMID- 24907752
TI  - Drug delivery property, bactericidal property and cytocompatibility of magnetic
      mesoporous bioactive glass.
AB  - A multifunctional magnetic mesoporous bioactive glass (MMBG) has been widely used
      for a drug delivery system, but its biological properties have been rarely
      reported. Herein, the effects of mesopores and Fe3O4 nanoparticles on drug
      loading-release property, bactericidal property and biocompatibility have been
      investigated by using mesoporous bioactive glass (MBG) and non-mesoporous
      bioactive glass (NBG) as control samples. Both MMBG and MBG have better drug
      loading efficiency than NBG because they possess ordered mesoporous channels, big
      specific surface areas and high pore volumes. As compared with MBG, the Fe3O4
      nanoparticles in MMBG not only provide magnetic property, but also improve
      sustained drug release property. For gentamicin-loaded MMBG (Gent-MMBG), the
      sustained release of gentamicin and the Fe3O4 nanoparticles minimize bacterial
      adhesion significantly and prevent biofilm formation against Staphylococcus
      aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Moreover, the
      magnetic Fe3O4 nanoparticles in MMBG can promote crucial cell functions such as
      cell adhesion, spreading and proliferation. The excellent biocompatibility and
      drug delivery property of MMBG suggest that Gent-MMBG has great potentials for
      treatment of implant-associated infections. 

PMID- 24907753
TI  - Electroanalytical studies on Cu (II) ion-selective sensor of coated pyrolytic
      graphite electrodes based on N2S2O2 and N2S2O3 heterocyclic benzothiazol ligands.
AB  - Benzothiazol based chelating ionophores such as 1,3-bis[2-(1,3-benzothiazol-2-yl)
      phenoxy]propane (L1) and 1,2'-bis[2-(1,3-benzothiazol-2-yl)-phenoxy]2
      ethoxyethane(L2) were synthesized and explored as neutral ionophores in the
      fabrication of Cu(2+) ion-selective electrodes. Variety of PVC-based electrodes
      i.e., polymeric membrane electrodes (PME), coated graphite electrodes (CGE) and
      coated pyrolytic graphite electrodes (CPGE) were prepared. The membranes having
      composition L1:PVC:1-CN:NaTPB=5:38:55:2 (w/w; mg) and L2:PVC:1-CN:NaTPB in the
      ratio of 6:39:53:2 are found to be exhibit the best potentiometric
      characteristics. The comparative studies of PME, CGE and CPGE based on L2 reveals
      that the CPGE is superior in terms of low detection limit of 6.30*10(-9) mol L(
      1) with a Nernstian slope of 29.5 mV decade(-1) of activity between pH2.0 to 8.5
      with a fast response time of 9s and could be used over a period of 5 months
      without any significant divergence in its potentiometric characteristics. The
      sensor has been employed for the estimation of Cu(2+) ion in real samples viz.,
      water, soil and herbal medicinal plants and besides this, the sensor was also
      used as an indicator electrode in the potentiometric determination of Cu(2+) with
      EDTA.

PMID- 24907754
TI  - Biocompatible core-shell electrospun nanofibers as potential application for
      chemotherapy against ovary cancer.
AB  - Polyvinyl alcohol/chitosan (PVA/CS) core-shell nanofibers are successfully
      fabricated by a simple coaxial electrospinning method, in which PVA forms the
      core layer and CS forms the shell layer. With the change of the feed ratio
      between PVA and CS, the surface morphology and the microstructures of the
      nanofibers are largely changed. The as-prepared core-shell fibers can be used as
      a carrier for doxorubicin (DOX) delivery. FT-IR analysis demonstrates that
      hydrogen bond between CS and PVA chains forms. The results of in vitro
      cytotoxicity test indicate that the core-shell fibers are completely
      biocompatible and the free DOX shows higher cytotoxicity than the DOX loaded
      nanofibers. The standing PVA/CS core-shell fibers remarkably promote the
      attachment, proliferation and spreading of human ovary cancer cells (SKOV3). Via
      observing by confocal laser scanning microscopy (CLSM), the DOX released from the
      fibers can be delivered into SKOV3 cell nucleus, which is significant for the
      future tumor therapy. And, the as-prepared fibers exhibit controlled release for
      loaded DOX via adjusting the feed ratio between PVA and CS, and the DOX loaded
      nanofibers are quite effective in prohibiting the SKOV3 ovary cells attachment
      and proliferation, which are potential for chemotherapy of ovary cancer. 

PMID- 24907755
TI  - Review: emerging developments in the use of bioactive glasses for treating
      infected prosthetic joints.
AB  - Bacterial contamination of implanted orthopedic prostheses is a serious
      complication that requires prolonged systemic antibiotic therapy, major surgery
      to remove infected implants, bone reconstruction, and considerable morbidity.
      Local delivery of high doses of antibiotics using poly(methyl methacrylate)
      (PMMA) cement as the carrier, along with systemic antibiotics, is the standard
      treatment. However, PMMA is not biodegradable, and it can present a surface on
      which secondary bacterial infection can occur. PMMA spacers used to treat deep
      implant infections must be removed after resolution of the infection. Alternative
      carrier materials for antibiotics that could also restore deficient bone are
      therefore of interest. In this article, the development of bioactive glass-based
      materials as a delivery system for antibiotics is reviewed. Bioactive glass is
      osteoconductive, converts to hydroxyapatite, and heals to hard and soft tissues
      in vivo. Consequently, bioactive glass-based carriers can provide the combined
      functions of controlled local antibiotic delivery and bone restoration. Recently
      developed borate bioactive glasses are of particular interest since they have
      controllable degradation rates coupled with desirable properties related to
      osteogenesis and angiogenesis. Such glasses have the potential for providing a
      new class of biomaterials, as substitutes for PMMA, in the treatment of deep bone
      infections. 

PMID- 24907756
TI  - Key parameters in blood-surface interactions of 3D bioinspired ceramic materials.
AB  - Direct contact of materials with blood components may trigger numerous processes
      which ultimately lead to hemolysis, clot formation and recruitment of
      inflammatory cells. In this study, the blood-surface interactions for two inert
      bioinspired ceramic scaffolds obtained from natural resources; biomorphic carbon
      and silicon carbides (bioSiC) from different origins have been studied. The
      response of the blood in contact with carbon is well known, however little has
      been identified on the influence of their 3D porous structure. Moreover, to our
      knowledge, there is no reference in the literature about the hemocompatibility of
      biomorphic silicon carbide as a porous scaffold. The experimental results showed
      the surface energy to be crucial to evaluate the hemocompatibility of a material
      however the surface topography and material porosity are also parameters to be
      considered. Surface roughness modifies clot formation whereas for protein
      adsorption total sample porosity seems to be the key parameter to be considered
      for hydrophilic materials (biomorphic silicon carbides), while the size of the
      pores determines the hemolytic response. 

PMID- 24907757
TI  - Characterization and antibacterial performance of electrodeposited chitosan
      vancomycin composite coatings for prevention of implant-associated infections.
AB  - Orthopaedic implant-associated infections are one of the most serious
      complications in orthopaedic surgery and a major cause of implant failure. In the
      present work, drug-eluting coatings based on chitosan containing various amounts
      of vancomycin were prepared by a cathodic electrophoretic deposition process on
      titanium foils. A three-step release mechanism of the antibiotic from the films
      in a phosphate-buffered saline solution was noticed. At the early stage, physical
      encapsulation of the drug in the hydrogel network controlled the release rate. At
      the late stage, however, in vitro degradation/deattachment of chitosan was
      responsible for the controlled release. Cytotoxicity evaluation of the drug
      eluting coatings via culturing in human osteosarcoma cells (MG-63 osteoblast-like
      cell line) showed no adverse effect on the biocompatibility. Antibacterial tests
      against Gram-positive Staphylococcus aureus also demonstrated that the infection
      risk of titanium foils was significantly reduced due to the antibiotic release.
      Additionally, in vitro electrochemical corrosion studies by polarization
      technique revealed that the corrosion current density was significantly lower for
      the titanium foils with drug-eluting coatings compared to that of uncoated
      titanium. 

PMID- 24907758
TI  - Synthesis of poly acrylic acid modified silver nanoparticles and their
      antimicrobial activities.
AB  - Poly acrylic acid modified silver (Ag/PAA) nanoparticles (NPs) have been
      successfully synthesized in the aqueous solution by using tannic acid as a
      reductant. The structure, morphology and composition of Ag/PAA NPs were
      characterized by various techniques such as X-ray powder diffraction (XRD),
      transmission electron microscopy (TEM), Fourier transform infrared spectroscopy
      (FTIR), ultraviolet-visible absorption spectroscopy (UV-vis) and thermogravimetry
      analysis (TGA). The results show that PAA/Ag NPs have a quasi-ball shape with an
      average diameter of 10 nm and exhibit well crystalline, and the reaction
      conditions have some effect on products morphology and size distribution. In
      addition, the as-synthesized Ag/PAA NPs antimicrobial activities against
      Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and
      Staphylococcus aureus (S. aureus) were evaluated by the methods of broth
      dilution, cup diffusion, optical density (OD600) and electron microscopy
      observation. The as-synthesized Ag/PAA NPs exhibit excellent antibacterial
      activity. The antimicrobial mechanism may be attributed to the damaging of
      bacterial cell membrane and causing leakage of cytoplasm.

PMID- 24907759
TI  - New alginic acid-atenolol microparticles for inhalatory drug targeting.
AB  - The inhalatory route allows drug delivery for local or systemic treatments in a
      noninvasively way. The current tendency of inhalable systems is oriented to dry
      powder inhalers due to their advantages in terms of stability and efficiency. In
      this work, microparticles of atenolol (AT, basic antihypertensive drug) and
      alginic acid (AA, acid biocompatible polyelectrolyte) were obtained by spray
      drying. Several formulations, varying the relative composition AT/AA and the
      total solid content of the atomized dispersions, were tested. The powders were
      characterized by: Fourier Transform Infrared Spectroscopy, Differential Scanning
      Calorimetry and Powder X-ray Diffraction, while also the following properties
      were measured: drug load efficiency, flow properties, particles size and density,
      moisture content, hygroscopicity and morphology. The ionic interaction between AA
      and AT was demonstrated, then the new chemical entity could improve the drug
      targeting to the respiratory membrane and increase its time residence due to the
      mucoadhesive properties of the AA polymeric chains. Powders exhibited high load
      efficiencies, low moisture contents, adequate mean aerodynamic diameters and high
      cumulative fraction of respirable particles (lower than 10 MUm).

PMID- 24907760
TI  - Novel magnesium alloy Mg-2La caused no cytotoxic effects on cells in
      physiological conditions.
AB  - Using several different in vitro assays, a new biodegradable magnesium alloy Mg
      2La, composed of 98% magnesium and 2% lanthanum, was investigated as a possible
      implant material for biomedical applications. An in vitro cytotoxicity test,
      according to EN ISO 10993-5/12, with L929 and human osteoblastic cells identified
      no toxic effects on cell viability at physiological concentrations (at 50%
      dilutions and higher). The metabolic activity of human osteoblasts in the 100%
      extract was decreased to <70% and was therefore rated as cytotoxic. The
      degradation rates of Mg-2La were evaluated in phosphate buffered saline and four
      different cell culture media. The degradation rates were shown to be influenced
      by the composition of the solution, and the addition of fetal bovine serum
      slightly accelerated the corrosive process. The results of these in vitro
      experiments suggest that Mg-2La is a promising candidate for use as an orthopedic
      implant material. 

PMID- 24907761
TI  - Enhanced cytotoxicity and apoptosis-induced anticancer effect of silibinin-loaded
      nanoparticles in oral carcinoma (KB) cells.
AB  - Silibinin (SIL) is a plant derived flavonoid isolated from the fruits and seeds
      of the milk thistle (Silybum marianum). Silibinin possesses a wide variety of
      biological applications including anticancer activities but poor aqueous
      solubility and poor bioavailability limit its potential and efficacy at the tumor
      sites. In the present study, silibinin was encapsulated in Eudragit(r) E (EE)
      nanoparticles in the presence of stabilizing agent polyvinyl alcohol (PVA) and
      its anticancer efficacy in oral carcinoma (KB) cells was studied. Silibinin
      loaded nanoparticles (SILNPs) were prepared by nanoprecipitation technique and
      characterized in terms of size distribution, morphology, surface charge,
      encapsulation efficiency and in vitro drug release. MTT assay revealed higher
      cytotoxic efficacy of SILNPs than free SIL in KB cells. Meanwhile, reactive
      oxygen species (ROS) determination revealed the significantly higher
      intracellular ROS levels in SILNPs treated cells compared to free SIL treated
      cells. Therefore, the differential cytotoxicity between SILNPs and SIL may be
      mediated by the discrepancy of intracellular ROS levels. Moreover, acridine
      orange (AO) and ethidium bromide (EB) dual staining and reduced mitochondrial
      membrane potential (MMP) confirmed the induction of apoptosis with nanoparticle
      treatment. Further, the extent of DNA damage (evaluated by comet assay) was
      significantly increased in SILNPs than free SIL in KB cells. Taken together, the
      present study suggests that silibinin-loaded nanoparticles can be used as an
      effective drug delivery system to produce a better chemopreventive response for
      the treatment of cancer. 

PMID- 24907762
TI  - Crystallization of dicalcium phosphate dihydrate with presence of glutamic acid
      and arginine at 37  degrees C.
AB  - The formations of non-metabolic stones, bones and teeth were seriously related to
      the morphology, size and surface reactivity of dicalcium phosphate dihydrate
      (DCPD). Herein, a facile biomimetic mineralization method with presence of
      glutamic acid and arginine was employed to fabricate DCPD with well-defined
      morphology and adjustable crystallite size. In reaction solution containing more
      arginine, crystallization of DCPD occurred with faster rate of nucleation and
      higher density of stacked layers due to the generation of more OH(-) ions after
      hydrolysis of arginine at 37  degrees C. With addition of fluorescein or acetone,
      the consumption of OH(-) ions or desolvation reaction of Ca(2+) ions was
      modulated, which resulted in the fabrication of DCPD with adjustable crystallite
      sizes and densities of stacked layers. In comparison with fluorescein-loading
      DCPD, dicalcium phosphate anhydrate was prepared with enhanced photoluminescence
      properties due to the reduction of self-quenching effect and regular arrangement
      of encapsulated fluorescein molecules. With addition of more acetone, DCPD was
      prepared with smaller crystallite size via antisolvent crystallization. The
      simulated process with addition of amino acids under 37  degrees C would shed
      light on the dynamic process of biomineralization for calcium phosphate
      compounds.

PMID- 24907763
TI  - Experimental and theoretical investigations of Lantana camara oil diffusion from
      polyacrylonitrile membrane for pulsatile drug delivery system.
AB  - Porous composite membrane of polyacrylonitrile (PAN) and Lantana camara essential
      oil was synthesized by solvent casting method. Stability of oil in PAN solution
      was measured by XiGo nano tool indicating constant relaxation time of 1487
      time/s. Pore size of few microns confirmed by electron microscopy was supported
      by atomic force microscopy indicating roughness factor of 0.9 nm. Contact angle
      of 2 degrees  inveterates superhydrophilicity of the composite membrane. Membrane
      showed excellent antibacterial activity against both Gram-positive Bacillus
      subtilis and Gram-negative Escherichia coli with a 7-10mm zone of inhibition. In
      vitro release of Lantana oil from the composite membrane was carried out in
      isotonic phosphate buffer solution (pH=7.4). Lantana oil was released for 9h, lag
      time of 3h with constant 33% release confirmed PAN membranes as potential system
      for pulsatile drug delivery applications. Diffusion of E-caryophyllene
      (antibacterial component of oil) which was studied through molecular simulation
      using Material Studio software ensued diffusion coefficient value of 1.11*10(-9)
      m(2)/s. Biocompatibility of the composite membrane was assessed by mouse
      embryonic fibroblast cell line (NIH 3T3) through MTT assay indicating more than
      91% viable cell even at 200 MUg/mL concentration. Such membranes can be
      efficiently used in biomedical applications as antibacterial and antifungal
      agent.

PMID- 24907764
TI  - Synthesis, characterization and foaming of PHEA-PLLA, a new graft copolymer for
      biomedical engineering.
AB  - In this study a chemical grafting procedure was set up in order to link high
      molecular weight poly L-lactic acid (PLLA) chains to the hydrophilic alpha,beta
      poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) backbone. A graft copolymer named
      PHEA-g-PLLA (or simply PHEA-PLLA) was obtained bearing a degree of derivatization
      of 1.0 mol.% of PLLA as grafted chain. This new hybrid derivative offers both the
      opportune crystallinity necessary for the production of scaffolds trough a
      thermally induced phase separation (TIPS) technique and the proper chemical
      reactivity to perform further functionalizations with bio-effectors and drugs.
      PHEA-PLLA porous scaffolds for tissue engineering applications were successfully
      obtained via TIPS and characterized. Structures with an open porosity and a good
      level of interconnection were detected. As the applicability of the scaffold is
      mainly dependent on its pore size, preliminary studies about the mechanisms
      governing scaffold's pore diameter were carried out.

PMID- 24907765
TI  - Short-term in vivo evaluation of zinc-containing calcium phosphate using a
      normalized procedure.
AB  - The effect of zinc-substituted calcium phosphate (CaP) on bone osteogenesis was
      evaluated using an in vivo normalized ISO 10993-6 protocol. Zinc-containing
      hydroxyapatite (ZnHA) powder with 0.3% by wt zinc (experimental group) and
      stoichiometric hydroxyapatite (control group) were shaped into cylindrical
      implants (2*6 mm) and were sintered at 1000  degrees C. Thermal treatment
      transformed the ZnHA cylinder into a biphasic implant that was composed of Zn
      substituted HA and Zn-substituted beta-tricalcium phosphate (ZnHA/betaZnTCP); the
      hydroxyapatite cylinder was a highly crystalline and poorly soluble HA implant.
      In vivo tests were performed in New Zealand White rabbits by implanting two
      cylinders of ZnHA/betaZnTCP in the left tibia and two cylinders of HA in the
      right tibia for 7, 14 and 28 days. Incorporation of 0.3% by wt zinc into CaP
      increased the rate of Zn release to the biological medium. Microfluorescence
      analyses (MUXRF-SR) using synchrotron radiation suggested that some of the Zn
      released from the biomaterial was incorporated into new bone near the implanted
      region. In contrast with previous studies, histomorphometric analysis did not
      show significant differences between the newly formed bone around ZnHA/betaZnTCP
      and HA due to the dissolution profile of Zn-doped CaP. Despite the great
      potential of Zn-containing CaP matrices for future use in bone regeneration,
      additional in vivo studies must be conducted to explain the mobility of zinc at
      the CaP surface and its interactions with a biological medium.

PMID- 24907766
TI  - Preparation and characterization of PHBV microsphere/45S5 bioactive glass
      composite scaffolds with vancomycin releasing function.
AB  - PHBV microsphere/45S5 bioactive glass (BG) composite scaffolds with drug release
      function were developed for bone tissue engineering. BG-based glass-ceramic
      scaffolds with high porosity (94%) and interconnected pore structure prepared by
      foam replication method were coated with PHBV microspheres (nominal diameter=3.5
      MUm) produced by water-in-oil-in-water double emulsion solvent evaporation
      method. A homogeneous microsphere coating throughout the porous structure of
      scaffolds was obtained by a simple dip coating method, using the slurry of PHBV
      microspheres in hexane. Compressive strength tests showed that the microsphere
      coating slightly improved the mechanical properties of the scaffolds. It was
      confirmed that the microsphere coating did not inhibit the bioactivity of the
      scaffolds in SBF. Hydroxyapatite crystals homogeneously grew not only on the
      struts of the scaffolds but also on the surface of microspheres within 7 days of
      immersion in SBF. Vancomycin was successfully encapsulated into the PHBV
      microspheres. The encapsulated vancomycin was released with a dual release
      profile involving a relatively low initial burst release (21%) and a sustained
      release (1 month), which is favorable compared to the high initial burst release
      (77%) and short release period (4 days) measured on uncoated scaffolds. The
      developed bioactive composite scaffold with drug delivery function has thus the
      potential to be used advantageously in bone tissue engineering.

PMID- 24907767
TI  - Electrostatic charges instigate 'concertina-like' mechanisms of molecular
      toughening in MaSp1 (spider silk) proteins.
AB  - According to a recent article authored by Ortega-Jimenez and Dudley [1], the
      capture success of spiders is in part due to electrostatic charges on the
      surfaces of insects that macroscopically deform the spider web and increase the
      chances of insect-web contact. In this brief communication, we further show that
      electrostatic charges instigate a molecular 'concertina-like' mechanism of
      deformation in MaSp1 protein, which effectively begins the toughening-up of
      dragline silk threads prior to insect-web contact. 

PMID- 24907768
TI  - Structural characterization of electrospun micro/nanofibrous scaffolds by liquid
      extrusion porosimetry: a comparison with other techniques.
AB  - Poly(epsilon-caprolactone) micro/nanofibrous scaffolds obtained by
      electrospinning technique from polymer solutions were characterized in terms of
      fiber diameter (as measured by scanning electron microscopy-SEM), pore size and
      its distribution (as measured by liquid extrusion porosimetry), and porosity (as
      determined by gravimetric measurement, liquid intrusion method, SEM image
      analysis and liquid extrusion porosimetry - LEP). Nonwoven micro/nanofibrous
      scaffolds were formed by uniform bead-free fibers with mean diameters in the
      range of 0.4 to 7 MUm. The results indicate that pore size and pore size
      distribution are strongly associated to fiber diameter. Porosity results were
      analyzed taking into account the accuracy and limitations of each method. LEP
      resulted as the most suitable technique for measuring through-pore diameter and
      porosity. In order to compare empirical data of pore size from LEP, a theoretical
      multiplanar model for stochastic fiber networks was applied. The results
      predicted by the model were in good agreement with the experimental data provided
      by LEP for mean diameters higher than 1 MUm. The present study shows the
      potential of LEP as a valuable instrumental technique for characterizing the
      porous structure of electrospun fibrous scaffolds.

PMID- 24907769
TI  - Growth of aluminum-free porous oxide layers on titanium and its alloys Ti-6Al-4V
      and Ti-6Al-7Nb by micro-arc oxidation.
AB  - The growth of oxides on the surfaces of pure Ti and two of its ternary alloys, Ti
      6Al-4V and Ti-6Al-7Nb, by micro-arc oxidation (MAO) in a pH 5 phosphate buffer
      was investigated. The primary aim was to form thick, porous, and aluminum-free
      oxide layers, because these characteristics favor bonding between bone and metal
      when the latter is implanted in the human body. On Ti, Ti-6Al-4 V, and Ti-6Al
      7Nb, the oxides exhibited breakdown potentials of about 200 V, 130 V, and 140 V,
      respectively, indicating that the oxide formed on the pure metal is the most
      stable. The use of the MAO procedure led to the formation of highly porous
      oxides, with a uniform distribution of pores; the pores varied in size, depending
      on the anodizing applied voltage and time. Irrespective of the material being
      anodized, Raman analyses allowed us to determine that the oxide films consisted
      mainly of the anatase phase of TiO2, and XPS results indicated that this oxide is
      free of Al and any other alloying element.

PMID- 24907770
TI  - Dermal administration of manganese porphyrin by iontophoresis.
AB  - The present study describes a technique for dermal administration of cationic
      manganese porphyrin (Mn-porphyrin), an antioxidant with superoxide dismutase
      (SOD) activity, in hairless mouse. In general, the stratum corneum on the surface
      of the skin represents a barrier to passive diffusion of therapeutic agents by
      standard dermal administration. The present study investigated whether, dermal
      administration of Mn-porphyrin solution using iontophoresis, the electrical
      dermal administration technique, could overcome this barrier. We visually
      confirmed that Mn-porphyrin had penetrated to the reverse side of the hairless
      mouse skin after iontophoresis for a short period. With prolonged iontophoresis,
      the ratio of detectable Mn-porphyrin solution on the reverse side of the hairless
      mouse skin increased. In the future, this technique could provide an innovative
      approach for delivery of this antioxidant in intractable disease. 

PMID- 24907771
TI  - Bacterial anti-adhesive properties of a monolayer of zwitterionic block copolymer
      micelles.
AB  - We report on bacterial anti-adhesive properties of a monolayer of block copolymer
      micelles (BCMs) with zwitterionic coronae and pH-responsive cores. BCMs were
      obtained by pH-induced self-assembly of selectively betainized poly[3-dimethyl
      (methacryloyloxyethyl) ammonium propane sulfonate-b-2-(diisopropylamino)ethyl
      methacrylate] (betaPDMA-b-PDPA) in aqueous solution above neutral pH. Monolayer
      films were self-assembled at pH 7.5 when betaPDMA-b-PDPA was in the micellar
      form. Bacterial anti-adhesive properties of the zwitterionic micellar coatings
      were examined against S. aureus through: i) a macroscopic test based on viable
      cell counting; ii) direct microscopic visualization of adherent bacteria by
      live/dead staining and iii) crystal violet staining to evaluate surface adherent
      biomass. 95% reduction in cell adhesion was observed by microscopy indicating the
      anti-adhesive properties of betaPDMA-b-PDPA micellar monolayer. Results obtained
      from the viable cell count assay and crystal violet staining showed similar
      trends and were in good agreement with the microscopy results. Such coatings are
      promising to impart both anti-adhesive and antimicrobial properties to a surface
      due to bacterial anti-adhesive properties of zwitterionic coronae and the
      potential of pH-responsive cores to release antimicrobial agents.

PMID- 24907772
TI  - On the distinct molecular architectures of dipping- and spray-LbL films
      containing lipid vesicles.
AB  - The introduction of spraying procedures to fabricate layer-by-layer (LbL) films
      has brought new possibilities for the control of molecular architectures and for
      making the LbL technique compliant with industrial processes. In this study we
      show that significantly distinct architectures are produced for dipping and spray
      LbL films of the same components, which included DODAB/DPPG vesicles. The films
      differed notably in their thickness and stratified nature. The electrical
      response of the two types of films to aqueous solutions containing erythrosin was
      also different. With multidimensional projections we showed that the impedance
      for the DODAB/DPPG spray-LbL film is more sensitive to changes in concentration,
      being therefore more promising as sensing units. Furthermore, with surface
      enhanced Raman scattering (SERS) we could ascribe the high sensitivity of the LbL
      films to adsorption of erythrosin. 

PMID- 24907773
TI  - Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma
      elasticum.
AB  - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder
      characterized by late onset and progressive calcification of elastic fibers in
      skin, eyes and the cardiovascular system, exemplifying a model for conditions
      characterized by soft tissue calcification. OBJECTIVE: The aim of our study was
      to characterize cellular inorganic pyrophosphate (PPi) homeostasis in PXE.
      METHODS: Gene expression of PPi metabolizing enzymes was determined by
      quantitative real-time PCR after incubation up to 21 days with or without
      addition of Na2HPO4. Extracellular and cytosolic PPi concentrations were measured
      by enzyme-linked bioluminescence assay. ALP and ENPP1 activity was determined
      spectrophotometrically. We further established a human cell culture model
      suitable for investigating PXE and related disorders without addition of
      artificial calcification triggers. RESULTS: Independently of the experimental
      conditions, PXE fibroblasts revealed a higher degree of matrix calcification. We
      observed that matrix calcification was associated with altered gene expression of
      PPi metabolizing enzymes in PXE fibroblasts. In this context, PXE fibroblasts
      exhibited significantly higher expression of ALP and OPN and reduced mRNA
      expression and activity of ENPP1. Here, for the first time cytosolic and
      extracellular PPi levels were shown to be strongly reduced in PXE fibroblasts. We
      further showed that PPi concentration in bovine and human sera additives had a
      strong impact on matrix calcification. In a last experimental line, we
      demonstrated that addition of PPi analogs reduced matrix calcification of PXE
      fibroblasts most likely by reducing ALP and OPN mRNA expression, restoring ENPP1
      activity and subsequently elevating PPi concentrations. CONCLUSION: The results
      of our study along with recent findings point to the essential role of PPi as the
      central regulatory metabolites preventing matrix calcification in PXE. But what
      remains to be determined is the underlying molecular mechanism leading to
      depletion of PPi in PXE. We further suggest that supplementation of PPi analogs
      might counteract pathological calcification in PXE and related disorders.

PMID- 24907775
TI  - A deceptive pneumothorax.

PMID- 24907774
TI  - Prevalence and patterns of smoking, alcohol use, and illicit drug use in young
      men who have sex with men.
AB  - BACKGROUND: Young men who have sex with men (YMSM) are substantially more likely
      to use illicit drugs and other substances compared to their heterosexual peers.
      Substance use during adolescence has critical implications for long-term physical
      and mental health, and among YMSM may lead to HIV infection. The goal of the
      current study was to describe lifetime and past six month prevalence and patterns
      of substance use across multiple substances in a community sample of racially
      diverse YMSM. METHODS: Participants were 450 YMSM aged 16-20 living in Chicago
      and surrounding areas who were recruited beginning December, 2009 using a
      modified form of respondent driven sampling. Analyses were conducted with
      multivariate logistic regression and latent class analysis (LCA). RESULTS:
      Prevalence of substance use was high in this sample of majority racial minority
      YMSM, and only 17.6% reported no substance use during the past six months. Black
      YMSM had lower prevalence of use of all substances except marijuana compared to
      White YMSM, while Latino YMSM had lower prevalence of alcohol, marijuana, and
      club drug use. Bisexual YMSM reported higher prevalence of cigarette smoking,
      stimulant use, and club drug use compared to gay/mostly gay YMSM but lower
      numbers of bisexual participants limited the ability to detect statistically
      significant differences. LCA found that YMSM fell into three general categories
      of substance users: alcohol and marijuana users, polysubstance users, and low
      marijuana users. CONCLUSIONS: Analyses reveal important group differences in
      prevalence and patterns of substance use in YMSM that have important implications
      for intervention.

PMID- 24907776
TI  - Does transosseous-equivalent rotator cuff repair biomechanically provide a "self
      reinforcement" effect compared with single-row repair?
AB  - BACKGROUND: Transosseous-equivalent (TOE) rotator cuff repair has been theorized
      to be "self-reinforcing" against potentially destructive and increasing tendon
      loads. The goal of this study was to biomechanically verify and characterize the
      effect of increasing tendon load on frictional resistance over a repaired
      footprint for single-row (SR) and TOE repair techniques. METHODS: In 10 fresh
      frozen human shoulders, TOE and SR supraspinatus tendon repairs were performed in
      each specimen. For all repairs, a pressure sensor was secured at the tendon
      footprint interface. The supraspinatus tendon was loaded with 0, 20, 40, 60, and
      80 N at 0 degrees  and 30 degrees  abduction. Paired t tests and multivariate
      regression analyses were used for comparisons. RESULTS: The SR repair had
      significant increases in footprint contact force, area, and pressure between each
      and all tendon-loading conditions (P < .05). The TOE repair similarly
      demonstrated increases in footprint contact force with increasing tendon load (P
      < .05). Comparing between repairs, TOE repair had more footprint contact force,
      area, pressure, and peak pressure at each load for both abduction angles (P <
      .05). With increasing load, the TOE repair had a significantly higher progression
      (slope) of footprint force and pressure compared with the SR repair. CONCLUSIONS:
      Self-reinforcing capacity in rotator cuff repair has been biomechanically
      characterized and verified. The TOE repair, with tendon-bridging sutures fixed
      medially and spanning the footprint, provides disproportionately more progressive
      footprint frictional resistance with increasing tendon loads compared with the SR
      repair secured over isolated fixation points. This self-reinforcing effect could
      help sustain structural integrity and potentially improve healing biology.

PMID- 24907777
TI  - Walking, orthoses and physical effort in a Swedish population with
      arthrogryposis.
AB  - PURPOSE: Excessive movements during walking have been observed by gait analysis
      in children with arthrogryposis (AMC) using orthoses compared to children using
      only shoes. The aim of this study was to evaluate energy expenditure and
      functional exercise capacity in children with AMC. METHODS: Twenty-four children
      with AMC and 25 typically developing (TD) children underwent oxygen measurement
      and the 6-minute walk test (6MWT). Children were divided into AMC1 using knee
      ankle-foot orthoses with locked knee joints (KAFO-LK); AMC2 KAFOs with open knee
      joints (KAFO-O) or ankle-foot orthoses (AFO); and AMC3 using shoes. RESULTS: The
      net non-dimensional oxygen cost (NNcost) was lower in TD (0.308) than in AMC2
      (0.455, n = 10) (p = 0.002). There were no differences in the net non-dimensional
      consumption (NNconsumption) or normalised walking velocity. The lowest
      NNconsumption (0.082), NNcost (0.385) and normalised walking velocity (0.214)
      were found in AMC1 (n = 3), but no statistical calculation was performed. In the
      6MWT, both AMC2 (402.7, n = 11) and AMC3 (476.8, n = 10) walked shorter distances
      (m) than TD (565.1) (p < 0.001 and p = 0.043, respectively). AMC2 (0.435) had
      lower normalised walking velocity than TD (0.564) (p < 0.001). CONCLUSIONS:
      Children with AMC using open KAFOs or AFOs (AMC2) had higher energy effort
      represented by significantly higher NNcost than TD, whereas AMC children
      requiring only shoes (AMC3) did not differ significantly from TD. To maintain the
      NNconsumption at an acceptable level, children using locked KAFOs (AMC1) slowed
      down their walking velocity. Compared to TD, the exercise capacity was lower in
      children with AMC using open KAFOs or AFOs and shoes, represented by lower
      walking velocity and shorter distance walked during the 6MWT.

PMID- 24907779
TI  - Evidence of the negative effect of sexual minority stigma on HIV testing among
      MSM and transgender women in San Salvador, El Salvador.
AB  - A cross sectional survey was administered to 670 men who have sex with men (MSM)
      and transgender women (TW) in San Salvador through respondent driven sampling to
      identify determinants of ever testing for HIV using a minority stress framework.
      A positive association was found between ever testing and older age [adjusted
      odds ratio (aOR) 2.10], past experience of sexual assault (aOR 2.92), perceiving
      that most social acquaintances had tested (aOR 1.81), and knowing a PLHIV (aOR
      1.94). A negative association was found between homelessness and ever testing
      (aOR 0.43). Among the MSM sub-sample (n = 506), similar results were found for
      older age (aOR 2.63), and past experience of sexual assault (aOR 2.56).
      Internalized homonegativity was negatively associated with ever testing for HIV
      among MSM (aOR 0.46), and HIV testing stigma and experienced provider
      discrimination further strengthened this relationship. It is important to
      mitigate sexual minority stigma in order to increase HIV testing among MSM.
      Future research should explore this construct among TW.

PMID- 24907778
TI  - Effects of messaging about multiple biomedical and behavioral HIV prevention
      methods on intentions to use among US MSM: results of an experimental messaging
      study.
AB  - Combining multiple biomedical and behavioral HIV prevention approaches is a
      priority for at-risk populations such as men who have sex with men (MSM), and it
      is essential to understand how receiving messages about multiple approaches
      impacts attitudes and intentions for their use. We examined whether receiving
      combinations of different HIV prevention messages produced differences in
      perceived benefits and costs of condom use, and in intentions to use condoms and
      biomedical prevention approaches. MSM (N = 803) were recruited online and were
      randomly assigned to view informational messages about one, two, or four of the
      following prevention options: pre-exposure prophylaxis (PrEP), non-occupational
      post-exposure prophylaxis (nPEP), rectal microbicides, and condoms. The number of
      HIV prevention messages did not produce differential attitudes and intentions
      regarding condoms, nor did it produce changes in attitudes towards unprotected
      sex. Receiving multiple messages was associated with greater intentions to use
      PrEP and nPEP, but not rectal microbicides. 

PMID- 24907780
TI  - Determinants of HIV outpatient service utilization: a systematic review.
AB  - Demands on HIV services are increasing as a consequence of the increased life
      expectancy of HIV patients in the highly active antiretroviral therapy era.
      Understanding the factors that influence utilization of ambulatory HIV services
      is useful for planning service provision. This study reviewed factors associated
      with utilization of hospital based HIV out-patient services. Studies reporting
      person-based utilization rates of HIV-specific outpatient services broken down by
      patient or healthcare characteristics were eligible for inclusion. The Andersen
      Behavioral Model was used to organize the information extracted into pre
      disposing, enabling and need components. Ten studies were included in the final
      review. Older age, private insurance, urban residence, lower CD4 counts, a
      diagnosis of AIDS, or anti-retroviral treatment were associated with higher
      utilization rates. The results of this review are consistent with existing
      knowledge regarding HIV patients' use of health services. Little information was
      identified on the influence of health service characteristics on utilization of
      out-patient services. 

PMID- 24907781
TI  - Reflection and transmission coefficients of a single layer in poroelastic media.
AB  - Wave propagation in poroelastic media is a subject that finds applications in
      many fields of research, from geophysics of the solid Earth to material science.
      In geophysics, seismic methods are based on the reflection and transmission of
      waves at interfaces or layers. It is a relevant canonical problem, which has not
      been solved in explicit form, i.e., the wave response of a single layer,
      involving three dissimilar media, where the properties of the media are described
      by Biot's theory. The displacement fields are recast in terms of potentials and
      the boundary conditions at the two interfaces impose continuity of the solid and
      fluid displacements, normal and shear stresses, and fluid pressure. The existence
      of critical angles is discussed. The results are verified by taking proper limits
      zero and 100% porosity-by comparison to the canonical solutions corresponding to
      single-phase solid (elastic) media and fluid media, respectively, and the case
      where the layer thickness is zero, representing an interface separating two
      poroelastic half-spaces. As examples, it was calculated the reflection and
      transmission coefficients for plane wave incident at a highly permeable and
      compliant fluid-saturated porous layer, and the case where the media are
      saturated with the same fluid. 

PMID- 24907782
TI  - Measuring static viscous permeability of porous absorbing materials.
AB  - Conventional acoustical methods for measuring the permeability or flow
      resistivity of a porous material require a priori estimation of the porosity. In
      this work, an acoustical method is presented in which a simplified expression
      (independent of both the frequency and porosity) for the transmitted waves at the
      Darcy's regime (low frequency range) is derived, and used for the inverse
      determination of both the viscous static permeability (or flow resistivity) and
      the thickness of air-saturated porous materials. The inverse problem is solved
      based on the least-square numerical method using experimental transmitted waves
      in time domain. Tests are performed using industrial plastic foams. Experimental
      and numerical validation results of this method are presented, which show the
      advantage of measuring the viscous permeability and thickness of a porous slab,
      without the required prior knowledge of the porosity, but by simply using the
      transmitted waves. 

PMID- 24907783
TI  - Linear elastic properties derivation from microstructures representative of
      transport parameters.
AB  - It is shown that three-dimensional periodic unit cells (3D PUC) representative of
      transport parameters involved in the description of long wavelength acoustic wave
      propagation and dissipation through real foam samples may also be used as a
      standpoint to estimate their macroscopic linear elastic properties. Application
      of the model yields quantitative agreement between numerical homogenization
      results, available literature data, and experiments. Key contributions of this
      work include recognizing the importance of membranes and properties of the base
      material for the physics of elasticity. The results of this paper demonstrate
      that a 3D PUC may be used to understand and predict not only the sound absorbing
      properties of porous materials but also their transmission loss, which is
      critical for sound insulation problems. 

PMID- 24907784
TI  - Effect of fracture compliance on wave propagation within a fluid-filled fracture.
AB  - Open and partially closed fractures can trap seismic waves. Waves propagating
      primarily within fluid in a fracture are sometimes called Krauklis waves, which
      are strongly dispersive at low frequencies. The behavior of Krauklis waves has
      previously been examined for an open, fluid-filled channel (fracture), but the
      impact of finite fracture compliance resulting from contacting asperities and
      porous fillings in the fracture (e.g., debris, proppants) has not been fully
      investigated. In this paper, a dispersion equation is derived for Krauklis wave
      propagation in a fracture with finite fracture compliance, using a modified
      linear-slip-interface model (seismic displacement-discontinuity model). The
      resulting equation is formally identical to the dispersion equation for the
      symmetric fracture interface wave, another type of guided wave along a fracture.
      The low-frequency solutions of the newly derived dispersion equations are in good
      agreement with the exact solutions available for an open fracture. The primary
      effect of finite fracture compliance on Krauklis wave propagation is to increase
      wave velocity and attenuation at low frequencies. These effects can be used to
      monitor changes in the mechanical properties of a fracture. 

PMID- 24907785
TI  - Asymptotic expansions for wavenumbers in orthotropic fluid-filled circular
      cylindrical shells for intermediate fluid loading.
AB  - Coupled wavenumbers in infinite fluid-filled isotropic and orthotropic
      cylindrical shells are considered. Using the Donnell-Mushtari (DM) theory for
      thin shells, compact and elegant asymptotic expansions for the wavenumbers are
      found at an intermediate fluid loading for both the coupled rigid-duct modes
      ("fluid-originated") and the coupled structural wavenumbers ("structure
      originated modes") over the entire frequency range where DM theory is valid. The
      coupled rigid-duct expansions are found to be valid for O(1) orthotropy and for
      all circumferential orders, whereas the coupled structural wavenumber expansions
      are valid for small orthotropy and for low circumferential orders. These two
      above results are then used to derive the expansions for a set of multiple
      complex roots that display a locking behavior at this intermediate fluid-loading.
      The expansions are matched with the numerical solutions of the coupled dispersion
      relation and the match is found to be good over most of the frequency range.

PMID- 24907786
TI  - Modelling of multiscale nonlinear interaction of elastic waves with three
      dimensional cracks.
AB  - This paper presents a nonlinear elastic material model able to simulate the
      nonlinear effects generated by the interaction of acoustic/ultrasonic waves with
      damage precursors and micro-cracks in a variety of materials. Such a constitutive
      model is implemented in an in-house finite element code and exhibits a multiscale
      nature where the macroscopic behavior of damaged structures can be represented
      through a contribution of a number of mesoscopic elements, which are composed by
      a statistical collection of microscopic units. By means of the semi-analytical
      Landau formulation and Preisach-Mayergoyz space representation, this multiscale
      model allows the description of the structural response under continuous harmonic
      excitation of micro-damaged materials showing both anharmonic and dissipative
      hysteretic effects. In this manner, nonlinear effects observed experimentally,
      such as the generation of both even and odd harmonics, can be reproduced. In
      addition, by using Kelvin eigentensors and eigenelastic constants, the wave
      propagation problem in both isotropic and orthotropic solids was extended to the
      three-dimensional Cartesian space. The developed model has been verified for a
      number of different geometrical and material configurations. Particularly, the
      influence of a small region with classical and non-classical elasticity and the
      variations of the input amplitudes on the harmonics generation were analyzed. 

PMID- 24907787
TI  - Modeling the receptivity of an air jet to transverse acoustic disturbance with
      application to musical instruments.
AB  - A simple analytical model for the interaction between a plane jet issued from a
      flue and a transverse acoustic disturbance is developed in this paper. The model
      is inspired by direct flow simulation results confronted to experimental data.
      The interaction is expected to take place in the vicinity of the separation
      points of the jet. The influence of the detailed geometry of the channel end on
      the jet receptivity is discussed, and more specifically the chamfer geometries
      found in flute-like musical instruments. The simplified model explains quite well
      the difference between the jet response of a flue with square edges compared to a
      chamfered flue exit. The effect of rounded, lip-like flue exit is not well
      captured by the model. 

PMID- 24907789
TI  - Lattice Boltzmann investigation of acoustic damping mechanism and performance of
      an in-duct circular orifice.
AB  - In this work, three-dimensional numerical simulations of acoustically excited
      flow through a millimeter-size circular orifice are conducted to assess its noise
      damping performance, with particular emphasis on applying the lattice Boltzmann
      method (LBM) as an alternative computational aeroacoustics tool. The model is
      intended to solve the discrete lattice Boltzmann equation (LBE) by using the
      pseudo-particle based technique. The LBE controls the particles associated with
      collision and propagation over a discrete lattice mesh. Flow variables such as
      pressure, density, momentum, and internal energy are determined by performing a
      local integration of the particle distribution at each time step. This is
      different from the conventional numerical investigation attempting to solve
      Navier-Stokes (NS) equations by using high order finite-difference or finite
      volume methods. Compared with the conventional NS solvers, one of the main
      advantages of LBM may be a reduced computational cost. Unlike frequency domain
      simulations, the present investigation is conducted in time domain, and the
      orifice damping behavior is quantified over a broad frequency range at a time by
      forcing an oscillating flow with multiple tones. Comparing the numerical results
      with those obtained from the theoretical models, large eddy simulation, and
      experimental measurements, good agreement is observed. 

PMID- 24907788
TI  - Acoustic pulse propagation in an urban environment using a three-dimensional
      numerical simulation.
AB  - Acoustic pulse propagation in outdoor urban environments is a physically complex
      phenomenon due to the predominance of reflection, diffraction, and scattering.
      This is especially true in non-line-of-sight cases, where edge diffraction and
      high-order scattering are major components of acoustic energy transport. Past
      work by Albert and Liu [J. Acoust. Soc. Am. 127, 1335-1346 (2010)] has shown that
      many of these effects can be captured using a two-dimensional finite-difference
      time-domain method, which was compared to the measured data recorded in an army
      training village. In this paper, a full three-dimensional analysis of acoustic
      pulse propagation is presented. This analysis is enabled by the adaptive
      rectangular decomposition method by Raghuvanshi, Narain and Lin [IEEE Trans.
      Visual. Comput. Graphics 15, 789-801 (2009)], which models sound propagation in
      the same scene in three dimensions. The simulation is run at a much higher usable
      bandwidth (nearly 450 Hz) and took only a few minutes on a desktop computer. It
      is shown that a three-dimensional solution provides better agreement with
      measured data than two-dimensional modeling, especially in cases where
      propagation over rooftops is important. In general, the predicted acoustic
      responses match well with measured results for the source/sensor locations. 

PMID- 24907790
TI  - On compressibility assumptions in aeroacoustic integrals: a numerical study with
      subsonic mixing layers.
AB  - Two assumptions commonly made in predictions based on Lighthill's formalism are
      investigated: A constant density in the quadrupole expression and the evaluation
      of the source quantity from incompressible simulations. Numerical predictions of
      the acoustic field are conducted in the case of a subsonic spatially evolving two
      dimensional mixing layer at Re = 400. Published results of the direct noise
      computation (DNC) of the flow are used as reference and input for hybrid
      approaches before the assumptions on density are progressively introduced.
      Divergence free velocity fields are obtained from an incompressible simulation of
      the same flow case, exhibiting the same hydrodynamic field as the DNC. For the
      tested values of the Mach number, hybrid predictions reproduce correctly the
      reference acoustic field, validating both assumptions in the source region.
      However, in the observer region, the inclusion of flow effects in the Lighthill
      source term is not preserved, which is illustrated through a comparison with the
      Kirchhoff wave-extrapolation formalism, and with the use of a convected Green
      function in the integration process. 

PMID- 24907791
TI  - Shear wave attenuation and micro-fluidics in water-saturated sand and glass
      beads.
AB  - An improvement in the modeling of shear wave attenuation and speed in water
      saturated sand and glass beads is introduced. Some dry and water-saturated
      materials are known to follow a constant-Q model in which the attenuation,
      expressed as Q(-1), is independent of frequency. The associated loss mechanism is
      thought to lie within the solid frame. A second loss mechanism in fluid-saturated
      porous materials is the viscous loss due to relative motion between pore fluid
      and solid frame predicted by the Biot-Stoll model. It contains a relaxation
      process that makes the Q(-1) change with frequency, reaching a peak at a
      characteristic frequency. Examination of the published measurements above 1 kHz,
      particularly those of Brunson (Ph.D. thesis, Oregon State University, Corvalis,
      1983), shows another peak, which is explained in terms of a relaxation process
      associated with the squirt flow process at the grain-grain contact. In the
      process of deriving a model for this phenomenon, it is necessary to consider the
      micro-fluidic effects associated with the flow within a thin film of water
      confined in the gap at the grain-grain contact and the resulting increase in the
      effective viscosity of water. The result is an extended Biot model that is
      applicable over a broad band of frequencies. 

PMID- 24907792
TI  - Characterization of underwater sounds produced by hydraulic and mechanical
      dredging operations.
AB  - Sound recordings were made of two dredging operations at hydrophone depths of 3
      and 9.1 m at distances up to 1.2 km from the source in shallow waters (<15 m) of
      New York Harbor. Sound sources included rock fracturing by a hydraulic cutterhead
      dredge and six distinct sources associated with a mechanical backhoe dredging
      operation during rock excavation. To place sound emitted from these dredges in
      perspective with other anthropogenic sounds, recordings were also made of several
      deep-draft commercial vessels. Results are presented as sound pressure levels
      (SPLs) in one-third octave versus range across the 20 Hz to 20 kHz frequency
      band. To address concerns for protection of fishery resource occupying the
      harbor, SPL were examined at frequency bands of 50-1000 Hz and 100-400 Hz, the
      ranges where the majority of fishes without hearing specializations detect sound
      and the range of greatest sensitivity, respectively. Source levels (dB re 1 MUPa
      1 m rms) were back calculated using fitted regression (15LogR). The strongest
      sound sources (180-188.9 dB) were emitted by commercial shipping. Rock fracturing
      produced a source level of 175 dB, whereas six distinct sources associated with
      rock excavation had source levels ranging from 164.2 to 179.4 dB re 1 MUPa-1 m
      (rms). 

PMID- 24907793
TI  - The effects of environmental variability and spatial sampling on the three
      dimensional inversion problem.
AB  - The overall goal of this work is to quantify the effects of environmental
      variability and spatial sampling on the accuracy and uncertainty of estimates of
      the three-dimensional ocean sound-speed field. In this work, ocean sound speed
      estimates are obtained with acoustic data measured by a sparse autonomous
      observing system using a perturbative inversion scheme [Rajan, Lynch, and Frisk,
      J. Acoust. Soc. Am. 82, 998-1017 (1987)]. The vertical and horizontal resolution
      of the solution depends on the bandwidth of acoustic data and on the quantity of
      sources and receivers, respectively. Thus, for a simple, range-independent ocean
      sound speed profile, a single source-receiver pair is sufficient to estimate the
      water-column sound-speed field. On the other hand, an environment with
      significant variability may not be fully characterized by a large number of
      sources and receivers, resulting in uncertainty in the solution. This work
      explores the interrelated effects of environmental variability and spatial
      sampling on the accuracy and uncertainty of the inversion solution though a set
      of case studies. Synthetic data representative of the ocean variability on the
      New Jersey shelf are used. 

PMID- 24907794
TI  - Observations regarding coarse sediment classification based on multi-beam echo
      sounder's backscatter strength and depth residuals in Dutch rivers.
AB  - This contribution investigates the behavior of two important riverbed sediment
      classifiers, derived from multi-beam echo-sounder (MBES)-operating at 300 kHz
      data, in very coarse sediment environments. These are the backscatter strength
      and the depth residuals. Four MBES data sets collected at different parts of
      rivers in the Netherlands are employed. From previous research the backscatter
      strength was found to increase for increasing mean grain sizes. Depth residuals,
      however, are often found to have lower values for coarser sediments.
      Investigation of the four data sets indicates that these statements are valid
      only for moderately coarse sediment such as sand. For very coarse sediments
      (e.g., coarse gravel) the backscatter strength is found to decrease and the depth
      residuals increase for increasing mean grain sizes. This is observed when the
      sediment mean grain size becomes significantly larger than the acoustic
      wavelength of the MBES (5 mm). Knowledge regarding this behavior is of high
      importance when using backscatter strength and depth residuals for sediment
      classification purposes as the reverse in behavior can induce ambiguity in the
      classification. 

PMID- 24907795
TI  - Estimates of the temporal and spatial variability of ocean sound speed on the New
      Jersey shelf.
AB  - Estimates of the spatial and temporal variability of ocean sound speed on the New
      Jersey shelf were obtained using acoustic signals measured by a set of freely
      drifting buoys. The range- and time-dependent inversion problem is
      computationally intensive and a linearized perturbative algorithm was applied to
      obtain results in an efficient manner. The inversion algorithm uses estimates of
      modal travel time to determine sound speed as a function of range and depth. In
      order to handle the high volume of data associated with the acoustic sensing
      network, the modal travel time estimation process was automated using an adaptive
      time-frequency signal processing method known as time-warping. Time-warping is a
      model-based transform that converts the frequency-dependent modal arrivals to
      monotones in the warped domain where they can be easily filtered. The data
      analyzed in this paper were collected on 16 March 2011 on the New Jersey shelf
      when the ocean was relatively well-mixed. While the observed sound-speed
      variations are small, both spatial and temporal trends are observed in the
      results. Furthermore, the estimated sound-speed profiles show good agreement with
      temporally and spatially collocated measurements. 

PMID- 24907796
TI  - Statistical inference of seabed sound-speed structure in the Gulf of Oman Basin.
AB  - Addressed is the statistical inference of the sound-speed depth profile of a
      thick soft seabed from broadband sound propagation data recorded in the Gulf of
      Oman Basin in 1977. The acoustic data are in the form of time series signals
      recorded on a sparse vertical line array and generated by explosive sources
      deployed along a 280 km track. The acoustic data offer a unique opportunity to
      study a deep-water bottom-limited thickly sedimented environment because of the
      large number of time series measurements, very low seabed attenuation, and
      auxiliary measurements. A maximum entropy method is employed to obtain a
      conditional posterior probability distribution (PPD) for the sound-speed ratio
      and the near-surface sound-speed gradient. The multiple data samples allow for a
      determination of the average error constraint value required to uniquely specify
      the PPD for each data sample. Two complicating features of the statistical
      inference study are addressed: (1) the need to develop an error function that can
      both utilize the measured multipath arrival structure and mitigate the effects of
      data errors and (2) the effect of small bathymetric slopes on the structure of
      the bottom interacting arrivals. 

PMID- 24907797
TI  - Markov-chain Monte Carlo identification of favorable design choices with
      application to anechoic coatings.
AB  - Global optimization methods can be used to numerically determine optimal design
      parameters for an object. However, this does not by itself give a good
      appreciation of other parameter choices that may be almost as good and even
      preferable from other points of view. In the present paper, Markov-chain Monte
      Carlo methods are used to go beyond the optimal solution and create an ensemble
      of object models in parameter space that covers a set of favorable models
      uniformly. In direct analogy with applications to Bayesian inversion with
      determination of an unknown posterior probability density, projections of the
      model ensemble onto parameter axes and planes are used to exhibit parameter
      sensitivities and dependencies. Design of anechoic rubber coatings, with cylinder
      cavities having axes in a lateral direction, is considered as a particular
      application. The anechoic effect is evaluated by the efficient layer-multiple
      scattering method, which is extended to handle cylinder scatterers of noncircular
      cross sections and mixed types. As anticipated by computed scattering and
      absorption cross sections for an isolated cavity, the favorable coatings have
      oblate cavity cross-section shapes, which is useful to achieve good low-frequency
      reflection reduction with a thin coating. 

PMID- 24907798
TI  - Using a coherent hydrophone array for observing sperm whale range,
      classification, and shallow-water dive profiles.
AB  - Sperm whales in the New England continental shelf and slope were passively
      localized, in both range and bearing, and classified using a single low-frequency
      (<2500 Hz), densely sampled, towed horizontal coherent hydrophone array system.
      Whale bearings were estimated using time-domain beamforming that provided high
      coherent array gain in sperm whale click signal-to-noise ratio. Whale ranges from
      the receiver array center were estimated using the moving array triangulation
      technique from a sequence of whale bearing measurements. Multiple concurrently
      vocalizing sperm whales, in the far-field of the horizontal receiver array, were
      distinguished and classified based on their horizontal spatial locations and the
      inter-pulse intervals of their vocalized click signals. The dive profile was
      estimated for a sperm whale in the shallow waters of the Gulf of Maine with 160 m
      water-column depth located close to the array's near-field where depth estimation
      was feasible by employing time difference of arrival of the direct and multiply
      reflected click signals received on the horizontal array. By accounting for
      transmission loss modeled using an ocean waveguide-acoustic propagation model,
      the sperm whale detection range was found to exceed 60 km in low to moderate sea
      state conditions after coherent array processing. 

PMID- 24907799
TI  - Acoustic capture-recapture method for towed acoustic surveys of echolocating
      porpoises.
AB  - Passive acoustic monitoring for cetaceans mainly employ fixed-location methods or
      point transect samplings; an acoustic survey from a moving platform to conduct
      line transects is less common. In this study, acoustic capture-recapture by
      combining a double-observer method with line transect sampling was performed to
      observe Yangtze finless porpoises. Two acoustic devices were towed with the
      distance between them varying 0.5 to 89.5 m. The conditional probabilities that
      both devices would detect the porpoises within the same time window were
      calculated. In a 1-s time window, it became smaller as the distance between the
      devices increased, approaching zero when the distance between them was more than
      50 m. It was considered that the devices with less than 50 m distance detected
      the same signals from the same animals, which means the identical detection. When
      the distance between them is too great, the recapture rate is reduced and the
      incidence of false matching may increase. Thus, a separation distance of around
      50 m between two devices in acoustic capture-recapture of Yangtze finless
      porpoises was recommended. Note that the performance of the double detections can
      change depending on the particular device used and on animal behaviors such as
      vocalizing interval, ship avoidance. 

PMID- 24907800
TI  - Using Gaussian mixture models to detect and classify dolphin whistles and pulses.
AB  - In recent years, a number of automatic detection systems for free-ranging
      cetaceans have been proposed that aim to detect not just surfaced, but also
      submerged, individuals. These systems are typically based on pattern-recognition
      techniques applied to underwater acoustic recordings. Using a Gaussian mixture
      model, a classification system was developed that detects sounds in recordings
      and classifies them as one of four types: background noise, whistles, pulses, and
      combined whistles and pulses. The classifier was tested using a database of
      underwater recordings made off the Spanish coast during 2011. Using cepstral
      coefficient-based parameterization, a sound detection rate of 87.5% was achieved
      for a 23.6% classification error rate. To improve these results, two parameters
      computed using the multiple signal classification algorithm and an
      unpredictability measure were included in the classifier. These parameters, which
      helped to classify the segments containing whistles, increased the detection rate
      to 90.3% and reduced the classification error rate to 18.1%. Finally, the
      potential of the multiple signal classification algorithm and unpredictability
      measure for estimating whistle contours and classifying cetacean species was also
      explored, with promising results. 

PMID- 24907801
TI  - Real and causal hysteresis elements.
AB  - Hysteresis is a phenomenon that has been observed across many different materials
      and situations. Under small-amplitude cyclical motion, classical hysteresis
      designates a constant loss per cycle over a wide range of frequencies. This is
      also consistent with an increase in losses or attenuation with frequency that is
      strictly proportional to the first power of frequency. Unfortunately, the
      classical (and simple) frequency domain description of hysteresis does not result
      in a real and causal impulse response, and therefore is not useful for predicting
      laboratory results. This problem has led to many errors as well as other more
      fruitful approaches over the years. The frequency domain requirements for
      hysteresis are re-examined and it is demonstrated that there is a family of
      solutions that provide real and causal impulse responses over some extended
      frequency range. The family is conveniently divided into highpass, lowpass, and
      bandpass causal systems. These are populated by closed form analytical solutions
      which can be applied to the prediction of motion and waves in hysteretic
      materials and systems. 

PMID- 24907802
TI  - Comparison of the transmission properties of self-similar, periodic, and random
      multilayers at normal incidence.
AB  - The effect of self-similarity on acoustic and elastic wave propagation at normal
      incidence is investigated using Classical Cantor and Fibonacci multilayered
      structures. They are made of two sorts of orthotropic plies having differently
      oriented orthotropic axes with respect to the propagation direction. The
      properties of their transmission coefficient are presented using a unidirectional
      numerical model based on a transfer matrix formalism. It was found that stack
      self-similarity influences the acoustic transmission properties. Transmission
      coefficients of self-similar stacks present a self-similar shape and behavior. A
      self-similar process, applied to layer orientation allows multilayered stacks to
      be created. A thickness-equivalent model was developed to compare these
      structures with standard self-similar multilayers which are finally compared to
      periodic and random stacks. The transmission coefficient of a deterministic self
      similar Fibonacci structure is similar to that of an averaged transmission
      coefficient of random stacks. 

PMID- 24907803
TI  - Characteristics of group velocities of backward waves in a hollow cylinder.
AB  - It is known that modes in axially uniform waveguides exhibit backward-propagation
      characteristics for which group and phase velocities have opposite signs. For
      elastic plates, group velocities of backward Lamb waves depend only on Poisson's
      ratio. This paper explores ways to achieve a large group velocity of a backward
      mode in hollow cylinders by changing the outer to inner radius ratio, in order
      that such a mode with strong backward-propagation characteristics may be used in
      acoustic logging tools. Dispersion spectra of guided waves in hollow cylinders of
      varying radii are numerically simulated to explore the existence of backward
      modes and to choose the clearly visible backward modes with high group
      velocities. Analyses of group velocity characteristics show that only a small
      number of low order backward modes are suitable for practical use, and the radius
      ratio to reach the highest group velocity corresponds to the accidental
      degeneracy of neighboring pure transverse and compressional modes at the
      wavenumber k = 0. It is also shown that large group velocities of backward waves
      are achievable in hollow cylinders made of commonly encountered materials, which
      may bring cost benefits when using acoustic devices which take advantage of
      backward-propagation effects. 

PMID- 24907804
TI  - Time-of-flight modeling of transversal ultrasonic scan of wood.
AB  - Time-of-flight is a time for an ultrasonic pulse to cross a sample. It contains
      valuable information about the mechanical properties of a material. For the
      ultrasonic pulse propagating in wood perpendicular to the grain the relation
      between the time-of-flight and the elastic constants is rather complex due to the
      strong anisotropicity of wood. With the help of some assumptions this relation
      can be established from the elastic theory. The analytical calculation results in
      a function which represents a change of time-of-flight when the direction of
      propagation shifts from the radial to the tangential direction while scanning a
      board crosswise. The function takes into account the location of the pith and the
      geometry of the growth rings. The measurement performed on a sample of European
      spruce confirms the theoretical prediction. 

PMID- 24907805
TI  - A broadband, capacitive, surface-micromachined, omnidirectional microphone with
      more than 200 kHz bandwidth.
AB  - A surface micromachined microphone is presented with 230 kHz bandwidth. The
      structure uses a 2.25 MUm thick, 315 MUm radius polysilicon diaphragm suspended
      above an 11 MUm gap to form a variable parallel-plate capacitance. The back
      cavity of the microphone consists of the 11 MUm thick air volume immediately
      behind the moving diaphragm and also an extended lateral cavity with a radius of
      504 MUm. The dynamic frequency response of the sensor in response to
      electrostatic signals is presented using laser Doppler vibrometry and indicates a
      system compliance of 0.4 nm/Pa in the flat-band of the response. The sensor is
      configured for acoustic signal detection using a charge amplifier, and signal-to
      noise ratio measurements and simulations are presented. A resolution of 0.80
      mPa/?Hz (32 dB sound pressure level in a 1 Hz bin) is achieved in the flat-band
      portion of the response extending from 10 kHz to 230 kHz. The proposed sensor
      design is motivated by defense and intelligence gathering applications that
      require broadband, airborne signal detection.

PMID- 24907806
TI  - Analysis of feedback control of piezoelectric transducers.
AB  - Velocity control feedback may be required for implementation in large underwater
      acoustic arrays to mitigate the effects of strong acoustic field coupling when
      specific beam pattern performance over a variety of operating conditions is
      desired. This paper presents an analysis of velocity control with piezoelectric
      loads using motional current monitoring [as an extension to Aronov, J. Acoust.
      Soc. Am. 119(6), 3822-3830 (2006) and Bachand, Brown, and Aronov, J. Acoust. Soc.
      Am. 124(4), 2568 (2008)], with particular interest in automated wideband acoustic
      beamforming. The analysis is applicable to other forms of motional feedback
      control such as accelerometer or displacement signal feedback. Topics presented
      include the control loop's effectiveness, stability criteria, and the array
      equations governing the acoustical outputs. The conditions that can cause
      negative radiation impedance are also presented, concluding that in any velocity
      control system with acoustic interactions, the likelihood of a transmit channel
      absorbing more energy than it is transmitting increases with the feedback loop
      gain. This fundamental limitation must be considered before developing any
      practical acoustic velocity control system with strong inter-element acoustic
      field coupling. 

PMID- 24907807
TI  - Experimental vibroacoustic testing of plane panels using synthesized random
      pressure fields.
AB  - The experimental reproduction of random pressure fields on a plane panel and
      corresponding induced vibrations is studied. An open-loop reproduction strategy
      is proposed that uses the synthetic array concept, for which a small array
      element is moved to create a large array by post-processing. Three possible
      approaches are suggested to define the complex amplitudes to be imposed to the
      reproduction sources distributed on a virtual plane facing the panel to be
      tested. Using a single acoustic monopole, a scanning laser vibrometer and a
      baffled simply supported aluminum panel, experimental vibroacoustic indicators
      such as the Transmission Loss for Diffuse Acoustic Field, high-speed subsonic and
      supersonic Turbulent Boundary Layer excitations are obtained. Comparisons with
      simulation results obtained using a commercial software show that the
      Transmission Loss estimation is possible under both excitations. Moreover and as
      a complement to frequency domain indicators, the vibroacoustic behavior of the
      panel can be studied in the wave number domain. 

PMID- 24907808
TI  - Determination of the in-plane components of motion in a Lamb wave from single
      axis laser vibrometry.
AB  - A method is proposed for determining in-plane components of motion in a Lamb wave
      from laser vibrometer measurements of surface motion out of plane. The approach
      relies on a frequency domain transformation that assumes knowledge only of the
      plate thickness and the bulk wave speeds. An outline of the relevant theory is
      followed by several validation case studies that generally affirm a useful level
      of accuracy and robust performance across a relatively wide frequency-thickness
      product range. In a comparison to the two-angle vibrometry approach, the proposed
      method is shown to be simpler to implement and to yield estimates with a
      consistently higher signal to noise ratio. The approach is then used to furnish
      estimates of the in-plane strains in Lamb waves propagating in an aluminum plate
      at frequencies below the first cut-off. These estimates are compared to strain
      measurements obtained from an adhesively bonded fiber Bragg grating. The
      agreement is shown to be excellent overall with an average discrepancy of less
      than 6%; however, systematic errors of twice that amount were recorded in the low
      frequency-thickness product regime. These low-frequency discrepancies are not
      consistent with known sources of experimental error and cannot be explained by
      shear-lag theory. 

PMID- 24907809
TI  - Aircraft noise and speech intelligibility in an outdoor living space.
AB  - Studies of effects on speech intelligibility from aircraft noise in outdoor
      places are currently lacking. To explore these effects, first-order ambisonic
      recordings of aircraft noise were reproduced outdoors in a pergola. The average
      background level was 47 dB LA eq. Lists of phonetically balanced words (LAS
      max,word = 54 dB) were reproduced simultaneously with aircraft passage noise (LAS
      max,noise = 72-84 dB). Twenty individually tested listeners wrote down each
      presented word while seated in the pergola. The main results were (i) aircraft
      noise negatively affects speech intelligibility at sound pressure levels that
      exceed those of the speech sound (signal-to-noise ratio, S/N < 0), and (ii) the
      simple A-weighted S/N ratio was nearly as good an indicator of speech
      intelligibility as were two more advanced models, the Speech Intelligibility
      Index and Glasberg and Moore's [J. Audio Eng. Soc. 53, 906-918 (2005)] partial
      loudness model. This suggests that any of these indicators is applicable for
      predicting effects of aircraft noise on speech intelligibility outdoors. 

PMID- 24907810
TI  - Particle velocity gradient based acoustic mode beamforming for short linear
      vector sensor arrays.
AB  - In this paper, a subtractive beamforming algorithm for short linear arrays of two
      dimensional particle velocity sensors is described. The proposed method extracts
      the highly directional acoustic modes from the spatial gradients of the particle
      velocity field measured at closely spaced sensors along the array. The number of
      sensors in the array limits the highest order of modes that can be extracted.
      Theoretical analysis and numerical simulations indicate that the acoustic mode
      beamformer achieves directivity comparable to the maximum directivity that can be
      obtained with differential microphone arrays of equivalent aperture. When
      compared to conventional delay-and-sum beamformers for pressure sensor arrays,
      the proposed method achieves comparable directivity with 70%-85% shorter
      apertures. Moreover, the proposed method has additional capabilities such as high
      front-back (port-starboard) discrimination, frequency and steer direction
      independent response, and robustness to correlated ambient noise. Small inter
      sensor spacing that results in very compact apertures makes the proposed
      beamformer suitable for space constrained applications such as hearing aids and
      short towed arrays for autonomous underwater platforms. 

PMID- 24907811
TI  - Real-time separation of non-stationary sound fields with pressure and particle
      acceleration measurements.
AB  - To extract the desired non-stationary sound field generated by a target source in
      the presence of disturbing sources, a real-time sound field separation method
      with pressure and particle acceleration measurements is proposed. In this method,
      the pressure and particle acceleration signals at a time instant are first
      measured on one measurement plane, where the particle acceleration is obtained by
      the finite difference approximation with the aid of an auxiliary measurement
      plane; then, the desired pressure signal generated by the target source at the
      same time instant can be extracted in a timely manner, by a simple superposition
      of the measured pressure and the convolution between the measured particle
      acceleration and the derived impulse response function. Thereby, the proposed
      method possesses a significant feature of real-time separation of non-stationary
      sound fields, which provides the potential to in situ analyze the radiation
      characteristics of a non-stationary source. The proposed method was examined
      through numerical simulation and experiment. Results demonstrated that the
      proposed method can not only extract the desired time-evolving pressure signal
      generated by the target source at any space point, but can also obtain the
      desired spatial distribution of the pressure field generated by the target source
      at any time instant. 

PMID- 24907812
TI  - Shallow-water sparsity-cognizant source-location mapping.
AB  - Using passive sonar for underwater acoustic source localization in a shallow
      water environment is challenging due to the complexities of underwater acoustic
      propagation. Matched-field processing (MFP) exploits both measured and model
      predicted acoustic pressures to localize acoustic sources. However, the ambiguity
      surface obtained through MFP contains artifacts that limit its ability to reveal
      the location of the acoustic sources. This work introduces a robust scheme for
      shallow-water source localization that exploits the inherent sparse structure of
      the localization problem and the use of a model characterizing the acoustic
      propagation environment. To this end, the underwater acoustic source-localization
      problem is cast as a sparsity-inducing stochastic optimization problem that is
      robust to model mismatch. The resulting source-location map (SLM) yields reduced
      ambiguities and improved resolution, even at low signal-to-noise ratios, when
      compared to those obtained via classical MFP approaches. An iterative solver
      based on block-coordinate descent is developed whose computational complexity per
      iteration is linear with respect to the number of locations considered for the
      SLM. Numerical tests illustrate the performance of the algorithm. 

PMID- 24907813
TI  - The role of auditory spectro-temporal modulation filtering and the decision
      metric for speech intelligibility prediction.
AB  - Speech intelligibility models typically consist of a preprocessing part that
      transforms stimuli into some internal (auditory) representation and a decision
      metric that relates the internal representation to speech intelligibility. The
      present study analyzed the role of modulation filtering in the preprocessing of
      different speech intelligibility models by comparing predictions from models that
      either assume a spectro-temporal (i.e., two-dimensional) or a temporal-only
      (i.e., one-dimensional) modulation filterbank. Furthermore, the role of the
      decision metric for speech intelligibility was investigated by comparing
      predictions from models based on the signal-to-noise envelope power ratio,
      SNRenv, and the modulation transfer function, MTF. The models were evaluated in
      conditions of noisy speech (1) subjected to reverberation, (2) distorted by phase
      jitter, or (3) processed by noise reduction via spectral subtraction. The results
      suggested that a decision metric based on the SNRenv may provide a more general
      basis for predicting speech intelligibility than a metric based on the MTF.
      Moreover, the one-dimensional modulation filtering process was found to be
      sufficient to account for the data when combined with a measure of across (audio)
      frequency variability at the output of the auditory preprocessing. A complex
      spectro-temporal modulation filterbank might therefore not be required for speech
      intelligibility prediction. 

PMID- 24907814
TI  - Loudness of time-varying stimuli with electric stimulation.
AB  - McKay, Henshall, Farrell, and McDermott [J. Acoust. Soc. Am. 113, 2054-2063
      (2003)] developed a practical method to estimate the loudness of periodic
      electrical signals presented through a cochlear implant. In the present work,
      this method was extended to time-varying sounds based on two models of time
      varying loudness for normal listeners. To fit the model parameters, loudness
      balancing data was collected with six cochlear implant listeners. The pulse rate
      of a modulated pulse train was adjusted to equalize its loudness to a reference
      stimulus. The stimuli were single-electrode time-limited pulse bursts, repeated
      at a rate of 50 Hz, with on-times varying between 2 and 20 ms. The parameters of
      two different models of time-varying loudness were fitted to the results. For
      each model, parameters defining the time windows over which the electrical pulses
      contribute to instantaneous loudness were optimized. In each case, a good fit was
      obtained with the loudness balancing results. Therefore, the practical method was
      successfully extended to time-varying sounds by combining it with existing models
      of time-varying loudness for acoustic stimulation. 

PMID- 24907816
TI  - A comparative study of Interaural Time Delay estimation methods.
AB  - The Interaural Time Delay (ITD) is an important binaural cue for sound source
      localization. Calculations of ITD values are obtained either from measured time
      domain Head-Related Impulse Responses (HRIRs) or from their frequency transform
      Head-Related Transfer Functions (HRTFs). Numerous methods exist in current
      literature, based on a variety of definitions and assumptions of the nature of
      the ITD as an acoustic cue. This work presents a thorough comparative study of
      the degree of variability between some of the most common methods for calculating
      the ITD from measured data. Thirty-two different calculations or variations are
      compared for positions on the horizontal plane for the HRTF measured on both a
      KEMAR mannequin and a rigid sphere. Specifically, the spatial variations of the
      methods are investigated. Included is a discussion of the primary potential
      causes of these differences, such as the existence of multiple peaks in the HRIR
      of the contra-lateral ear for azimuths near the inter-aural axis due to multipath
      propagation and head/pinnae shadowing. 

PMID- 24907815
TI  - Assessing the effects of temporal coherence on auditory stream formation through
      comodulation masking release.
AB  - Recent studies of auditory streaming have suggested that repeated synchronous
      onsets and offsets over time, referred to as "temporal coherence," provide a
      strong grouping cue between acoustic components, even when they are spectrally
      remote. This study uses a measure of auditory stream formation, based on
      comodulation masking release (CMR), to assess the conditions under which a loss
      of temporal coherence across frequency can lead to auditory stream segregation.
      The measure relies on the assumption that the CMR, produced by flanking bands
      remote from the masker and target frequency, only occurs if the masking and
      flanking bands form part of the same perceptual stream. The masking and flanking
      bands consisted of sequences of narrowband noise bursts, and the temporal
      coherence between the masking and flanking bursts was manipulated in two ways:
      (a) By introducing a fixed temporal offset between the flanking and masking bands
      that varied from zero to 60 ms and (b) by presenting the flanking and masking
      bursts at different temporal rates, so that the asynchronies varied from burst to
      burst. The results showed reduced CMR in all conditions where the flanking and
      masking bands were temporally incoherent, in line with expectations of the
      temporal coherence hypothesis. 

PMID- 24907817
TI  - Nonuniform temporal weighting of interaural time differences in 500 Hz tones.
AB  - The discrimination and lateralization of interaural time differences (ITD) in
      rapidly modulated high-frequency sounds is dominated by cues present in the
      initial portion of the sound (i.e., at sound onset). The importance of initial
      ITD at low frequencies is, however, less clear. Here, ITD discrimination
      thresholds were measured in 500 Hz pure tones with diotic envelopes and static or
      dynamic fine-structure ITD. Static-ITD thresholds improved as tone duration
      increased from 40 to 640 ms but by an amount less than expected from uniform
      temporal weighting of binaural information. Dynamic conditions eliminated ITD
      from either the beginning or end of the sound by presenting slightly different
      frequencies to the two ears. While overall thresholds were lower when ITD was
      available at sound onset than when it was not, listeners differed appreciably in
      that regard. The results demonstrate that weighting of ITD is not temporally
      uniform. Instead, for many listeners, ITD discrimination at 500 Hz appears
      dominated by ITD cues present in the initial part of the sound. To a variable
      degree, other listeners rely more equally on ITD cues occurring near sound onsets
      and offsets, although no listeners appear to utilize such cues uniformly
      throughout the sound's duration. 

PMID- 24907819
TI  - Auditory acclimatization and hearing aids: late auditory evoked potentials and
      speech recognition following unilateral and bilateral amplification.
AB  - The aim of this study was to investigate changes in central auditory processing
      following unilateral and bilateral hearing aid fitting using a combination of
      physiological and behavioral measures: late auditory event-related potentials
      (ERPs) and speech recognition in noise, respectively. The hypothesis was that for
      fitted ears, the ERP amplitude would increase over time following hearing aid
      fitting in parallel with improvement in aided speech recognition. The N1 and P2
      ERPs were recorded to 500 and 3000 Hz tones presented at 65, 75, and 85 dB sound
      pressure level to either the left or right ear. New unilateral and new bilateral
      hearing aid users were tested at the time of first fitting and after 12 weeks
      hearing aid use. A control group of long-term hearing aid users was tested over
      the same time frame. No significant changes in the ERP were observed for any
      group. There was a statistically significant 2% improvement in aided speech
      recognition over time for all groups, although this was consistent with a general
      test-retest effect. This study does not support the existence of an
      acclimatization effect observable in late ERPs following 12 weeks' hearing aid
      use. 

PMID- 24907818
TI  - The perception of apparent auditory source width in hearing-impaired adults.
AB  - In a previous study [Whitmer, Seeber and Akeroyd, J. Acoust. Soc. Am. 132, 369
      379 (2012)], it was demonstrated that older hearing-impaired (HI) listeners
      produced visual sketches of headphone-presented noises that were insensitive to
      changes in interaural coherence. The current study further explores this
      insensitivity by comparing (a) binaural temporal fine-structure (TFS) resolution
      and (b) sound localization precision to (c) auditory source width judgments.
      Thirty-five participants aged 26-81 years with normal to moderately impaired
      hearing (a) discriminated interaurally phase-shifted tones from diotic tones
      presented over headphones, (b) located 500-ms speech-spectrum filtered click
      trains presented over loudspeakers between +/-30 degrees  in quiet, and (c)
      sketched the perceived width of low-pass, high-pass, and speech-spectrum noise
      stimuli presented over loudspeakers from 0 degrees  and simultaneously from +/-45
      degrees  at attenuations of 0-20 dB to generate partially coherent stimuli. The
      results showed a decreasing sensitivity to width with age and impairment which
      was related to binaural TFS threshold: the worse one's threshold-which was
      correlated with age-the less the perceived width increased with decreasing
      interaural coherence. These results suggest that senescent changes to the
      auditory system do not necessarily lead to perceptions of broader, more diffuse
      sound images based on interaural coherence. 

PMID- 24907820
TI  - Acoustic correlates of vowel intelligibility in clear and conversational speech
      for young normal-hearing and elderly hearing-impaired listeners.
AB  - The present investigation carried out acoustic analyses of vowels in clear and
      conversational speech produced by 41 talkers. Mixed-effects models were then
      deployed to examine relationships among acoustic and perceptual data for these
      vowels. Acoustic data include vowel duration, steady-state formant frequencies,
      and two measures of dynamic formant movement. Perceptual data consist of vowel
      intelligibility in noise for young normal-hearing and elderly hearing-impaired
      listeners, as reported by Ferguson in 2004 and 2012 [J. Acoust. Soc. Am. 116,
      2365-2373 (2004); J. Speech Lang. Hear. Res. 55, 779-790 (2012)], respectively.
      Significant clear speech effects were observed for all acoustic metrics, although
      not all measures changed for all vowels and considerable talker variability was
      observed. Mixed-effects analyses revealed that the contribution of duration and
      steady-state formant information to vowel intelligibility differed for the two
      listener groups. This outcome is consistent with earlier research suggesting that
      hearing loss, and possibly aging, alters the way acoustic cues are used for
      identifying vowels. 

PMID- 24907821
TI  - The effect of language experience on perceptual normalization of Mandarin tones
      and non-speech pitch contours.
AB  - Context-dependent pitch perception helps listeners recognize tones produced by
      speakers with different fundamental frequencies (f0s). The role of language
      experience in tone normalization remains unclear. In this cross-language study of
      tone normalization, native Mandarin and English listeners were asked to recognize
      Mandarin Tone 1 (high-flat) and Tone 2 (mid-rising) with a preceding Mandarin
      sentence. To further test whether context-dependent pitch perception is speech
      specific or domain-general, both language groups were asked to identify non
      speech flat and rising pitch contours with a preceding non-speech flat pitch
      contour. Results showed that both Mandarin and English listeners made more rising
      responses with non-speech than with speech stimuli, due to differences in
      spectral complexity and listening task between the two stimulus types. English
      listeners made more rising responses than Mandarin listeners with both speech and
      non-speech stimuli. Contrastive context effects (more rising responses in the
      high-f0 context than in the low-f0 context) were found with both speech and non
      speech stimuli for Mandarin listeners, but not for English listeners. English
      listeners' lack of tone experience may have caused more rising responses and
      limited use of context f0 cues. These results suggest that context-dependent
      pitch perception in tone normalization is domain-general, but influenced by long
      term language experience. 

PMID- 24907823
TI  - Drawing melodies: evaluation of chironomic singing synthesis.
AB  - Cantor Digitalis, a real-time formant synthesizer controlled by a graphic tablet
      and a stylus, is used for assessment of melodic precision and accuracy in singing
      synthesis. Melodic accuracy and precision are measured in three experiments for
      groups of 20 and 28 subjects. The task of the subjects is to sing musical
      intervals and short melodies, at various tempi, using chironomy (hand-controlled
      singing), mute chironomy (without audio feedback), and their own voices. The
      results show the high accuracy and precision obtained by all the subjects for
      chironomic control of singing synthesis. Some subjects performed significantly
      better in chironomic singing compared to natural singing, although other subjects
      showed comparable proficiency. For the chironomic condition, mean note accuracy
      is less than 12 cents and mean interval accuracy is less than 25 cents for all
      the subjects. Comparing chironomy and mute chironomy shows that the skills used
      for writing and drawing are used for chironomic singing, but that the audio
      feedback helps in interval accuracy. Analysis of blind chironomy (without visual
      reference) indicates that a visual feedback helps greatly in both note and
      interval accuracy and precision. This study demonstrates the capabilities of
      chironomy as a precise and accurate mean for controlling singing synthesis. 

PMID- 24907822
TI  - Development of speech glimpsing in synchronously and asynchronously modulated
      noise.
AB  - This study investigated development of the ability to integrate glimpses of
      speech in modulated noise. Noise was modulated synchronously across frequency or
      asynchronously such that when noise below 1300 Hz was "off," noise above 1300 Hz
      was "on," and vice versa. Asynchronous masking was used to examine the ability of
      listeners to integrate speech glimpses separated across time and frequency. The
      study used the Word Intelligibility by Picture Identification (WIPI) test and
      included adults, older children (age 8-10 yr) and younger children (5-7 yr).
      Results showed poorer masking release for the children than the adults for
      synchronous modulation but not for asynchronous modulation. It is possible that
      children can integrate cues relatively well when all intervals provide at least
      partial speech information (asynchronous modulation) but less well when some
      intervals provide little or no information (synchronous modulation). Control
      conditions indicated that children appeared to derive less benefit than adults
      from speech cues below 1300 Hz. This frequency effect was supported by
      supplementary conditions where the noise was unmodulated and the speech was low-
      or high-pass filtered. Possible sources of the developmental frequency effect
      include differences in frequency weighting, effective speech bandwidth, and the
      signal-to-noise ratio in the unmodulated noise condition. 

PMID- 24907829
TI  - Robust direction-of-arrival by matched-lags, applied to gunshots.
AB  - This work investigates the direction-of-arrival problem. A time-delay-estimate
      (TDE) obtained from a peak of a correlation function is subject to two types of
      error: type I, approximation errors, and type II, errors due to spurious signals.
      The iterative least-squares algorithm tentatively selects spatially coherent
      subsets of TDEs containing no type II errors and minor contributions of type I
      errors ("matched-lags"). Simulations use a seven-microphone array and a gunshot
      signal. The evaluation methodology is rigorous, comparing empirical distribution
      functions of estimation error of algorithms through two-sample, one-sided
      Kolmogorov-Smirnov tests, and quantifying differences with Cohen's D. The
      direction-of-arrival estimate is improved, specifically at low signal-to-noise
      ratios. 

PMID- 24907828
TI  - Enhancement of speech intelligibility in reverberant rooms: role of amplitude
      envelope and temporal fine structure.
AB  - The temporal envelope and fine structure of speech make distinct contributions to
      the perception of speech in normal-hearing listeners, and are differentially
      affected by room reverberation. Previous work has demonstrated enhanced speech
      intelligibility in reverberant rooms when prior exposure to the room was
      provided. Here, the relative contributions of envelope and fine structure cues to
      this intelligibility enhancement were tested using an open-set speech corpus and
      virtual auditory space techniques to independently manipulate the speech cues
      within a simulated room. Intelligibility enhancement was observed only when the
      envelope was reverberant, indicating that the enhancement is envelope-based. 

PMID- 24907830
TI  - Time-domain acoustic contrast control design with response differential
      constraint in personal audio systems.
AB  - The acoustic contrast control (ACC) approach is applied to reproduce the focused
      sound in personal audio systems utilizing an array of loudspeakers. A time-domain
      design of ACC is developed here for broadband input signals, where a response
      differential term is introduced to control the frequency response. Based on
      experimental results in an anechoic chamber, the proposed method demonstrates the
      potential capability to provide excellent acoustic contrast over the continuous
      frequency and maintain a flat frequency response. Furthermore, compared with the
      previous method, fewer parameters need to be tuned in the proposed method. 

PMID- 24907831
TI  - Image source detection for geoacoustic inversion by the Teager-Kaiser energy
      operator.
AB  - This letter presents an improvement of the image source method for geoacoustic
      inversion. The algorithm is based on the Teager-Kaiser energy operator which
      amplifies the discontinuities in signals while the soft transitions are reduced.
      This property is exploited for accurate detection of time arrivals and thus for
      location of the image sources. The effectiveness of the method is shown on both
      synthetic and real data and the inversion results are, overall, in good agreement
      with ground truth and other inversion results with a significant reduction of
      computation time. 

PMID- 24907832
TI  - Coffee roasting acoustics.
AB  - Cracking sounds emitted by coffee beans during the roasting process were recorded
      and analyzed to investigate the potential of using the sounds as the basis for an
      automated roast monitoring technique. Three parameters were found that could be
      exploited. Near the end of the roasting process, sounds known as "first crack"
      exhibit a higher acoustic amplitude than sounds emitted later, known as "second
      crack." First crack emits more low frequency energy than second crack. Finally,
      the rate of cracks appearing in the second crack chorus is higher than the rate
      in the first crack chorus. 

PMID- 24907833
TI  - Syllabic reduction in Mandarin and English speech.
AB  - This study examined whether language specific properties may lead to cross
      language differences in the degree of phonetic reduction. Rates of syllabic
      reduction (defined here as reduction in which the number of syllables pronounced
      is less than expected based on canonical form) in English and Mandarin were
      compared. The rate of syllabic reduction was higher in Mandarin than English.
      Regardless of language, open syllables participated in reduction more often than
      closed syllables. The prevalence of open syllables was higher in Mandarin than
      English, and this phonotactic difference could account for Mandarin's higher rate
      of syllabic reduction. 

PMID- 24907834
TI  - An eigenvector-based test for local stationarity applied to array processing.
AB  - In sonar array processing, a challenging problem is the estimation of the data
      covariance matrix in the presence of moving targets in the water column, since
      the time interval of data local stationarity is limited. This work describes an
      eigenvector-based method for proper data segmentation into intervals that exhibit
      local stationarity, providing data-driven higher bounds for the number of
      snapshots available for computation of time-varying sample covariance matrices.
      Application of the test is illustrated with simulated data in a horizontal array
      for the detection of a quiet source in the presence of a loud interferer. 

PMID- 24907835
TI  - Selection of spectral compressive operator for vector Taylor series-based model
      adaptation in noisy environments.
AB  - This letter investigates the impact of spectral compression on the vector Taylor
      series-based model adaptation algorithm. Unlike mel-frequency cepstral
      coefficients obtained by the logarithmic compression, the fractional power
      compression is used for extracting features. Since the relationship between
      acoustic models for clean and noisy speech depends on nonlinearity of the
      spectrum, it is important to select an appropriate compressive operator in the
      model adaptation. In this letter, the dependency of spectral nonlinearity on the
      speech recognition system is analyzed in various noisy environments. Experimental
      results confirm that the replacement of the compressive operator improves the
      performance of the model adaptation. 

PMID- 24907836
TI  - Planar microphone based on piezoelectric electrospun poly(gamma-benzyl-alpha,L
      glutamate) nanofibers.
AB  - Velocity and pressure microphones composed of piezoelectric poly(gamma-benzyl
      alpha,L-glutamate) (PBLG) nanofibers were produced by adhering a single layer of
      PBLG film to a Mylar diaphragm. The device exhibited a sensitivity of -60 dBV/Pa
      in air, and both pressure and velocity response showed a broad frequency response
      that was primarily controlled by the stiffness of the supporting diaphragm. The
      pressure microphone response was +/-3 dB between 200 Hz and 4 kHz when measured
      in a semi-anechoic chamber. Thermal stability, easy fabrication, and simple
      design make this single element transducer ideal for various applications
      including those for underwater and high temperature use. 

PMID- 24907837
TI  - Laser-induced acoustic point source for accurate impulse response measurements
      within the audible bandwidth.
AB  - Laser induced air breakdown is proposed as a sound source for accurate impulse
      response measurements. Within the audible bandwidth, the source is repeatable,
      broadband, and omnidirectional. The applicability of the source was evaluated by
      measuring the impulse response of a room. The proposed source provides a more
      accurate temporal and spatial representation of room reflections than
      conventional loudspeakers due to its omnidirectionality, negligible size and
      short pulse duration. 

PMID- 24907838
TI  - The effects of reverberant self- and overlap-masking on speech recognition in
      cochlear implant listeners.
AB  - Many cochlear implant (CI) listeners experience decreased speech recognition in
      reverberant environments [Kokkinakis et al., J. Acoust. Soc. Am. 129(5), 3221
      3232 (2011)], which may be caused by a combination of self- and overlap-masking
      [Bolt and MacDonald, J. Acoust. Soc. Am. 21(6), 577-580 (1949)]. Determining the
      extent to which these effects decrease speech recognition for CI listeners may
      influence reverberation mitigation algorithms. This study compared speech
      recognition with ideal self-masking mitigation, with ideal overlap-masking
      mitigation, and with no mitigation. Under these conditions, mitigating either
      self- or overlap-masking resulted in significant improvements in speech
      recognition for both normal hearing subjects utilizing an acoustic model and for
      CI listeners using their own devices. 

PMID- 24907839
TI  - Identifying concert halls from source presence vs room presence.
AB  - Identification of concert halls was studied to uncover whether the early or late
      part of the acoustic response is more salient in a hall's fingerprint. A
      listening test was conducted with auralizations of measured halls using full,
      hybrid, and truncated impulse responses convolved with anechoic symphonic music.
      Subjects identified halls more reliably based on differences in early responses
      rather than late responses, although varying the late response had more effect on
      acoustic parameters. The results suggest that in a typical situation with running
      symphonic music, the early response determines the perceptual fingerprint of a
      hall more than the late response. 

PMID- 24907840
TI  - Coherence extrapolation for underwater ambient noise.
AB  - This paper considers extrapolation of the vertical coherence of surface-generated
      oceanic ambient noise to simulate measurements made on a longer sensor array. The
      extrapolation method consists of projecting the noise coherence measured with a
      limited aperture array into the domain spanned by prolate spheroidal wave
      functions, which are an orthogonal basis defined by array parameters and the
      noise frequency. Using simulated data corresponding to selected multi-layered
      seabeds as ground truth, the performance of the extrapolation method is explored.
      Application of the technique is also demonstrated on experimental data. 

PMID- 24907841
TI  - Three-dimensional urban acoustic simulations and scale-model measurements over
      real-life topography.
AB  - Comparisons of finite-difference time-domain sound propagation simulations over
      real-life urban topography with scale-model experimental measurements are
      performed. A 1:100 scale model for the measurements and full-scale input geometry
      for the simulations are created by using digital geographic datasets. The sound
      pressure levels obtained by the measurements and simulations resulted in
      approximately 2 dB of root mean square error in the 125 and 250 Hz octave bands,
      and 4 dB in 500 Hz. Visualizations of a low-frequency sound propagation case by
      the measurement and simulation clearly show the wave phenomena caused by
      buildings and natural terrain. 

PMID- 24907842
TI  - Broadband performance of superdirective delay-and-sum beamformers steered to end
      fire.
AB  - Linear arrays steered to end-fire provide superdirective robust performance if a
      constraint is imposed on the white-noise gain. Filter-and-sum beamformers achieve
      the maximum constrained directivity by tuning their complex weights over the
      frequency. Delay-and-sum beamformers have simpler structures, but their weights
      are fixed and optimized at a given frequency. This letter investigates the
      constrained directivity provided over a broad band by different delay-and-sum
      techniques. Complex weights and analytic signals attain near-optimal broadband
      performance over four octaves. Oversteered arrays using real weights and signals
      were found to attain superdirective performance over approximately two octaves.
      Hearing aids and directional hydrophones are potential applications for the
      considered arrays. 

PMID- 24907843
TI  - Sound pressure around dipole source above porous surface.
AB  - A technique for in situ measurements of acoustic properties of a fibrous porous
      material is proposed in this paper. Proposed technique exploits a directivity
      pattern of a dipole source in its very near field. Theoretical analysis for the
      proposed technique is based on the Rayleigh integral with a complex reflection
      included. Results are compared with results of FEM analysis and show that flow
      resistivity of a porous material placed in the very near field of the dipole
      source has significant influence on the sound pressure at its ring. Results
      provide an excellent starting point for the design of the sensor for sound
      absorption. 

PMID- 24907844
TI  - Acoustic visualizations using surface mapping.
AB  - Sound visualizations have been an integral part of room acoustics studies for
      more than a century. As acoustic measurement techniques and knowledge of hearing
      evolve, acousticians need more intuitive ways to represent increasingly complex
      data. Microphone array processing now allows accurate measurement of spatio
      temporal acoustic properties. However, the multidimensional data can be a
      challenge to display coherently. This letter details a method of mapping visual
      representations of acoustic reflections from a receiver position to the surfaces
      from which the reflections originated. The resulting animations are presented as
      a spatial acoustic analysis tool. 

PMID- 24907845
TI  - Positive expectation in the processing of allophones.
AB  - Does native knowledge introduce a perceptual bias against allophones that
      mismatch their context? In German, [x] only occurs after back vowels, while [c]
      occurs elsewhere. German and English listeners heard "allophonic" ([c-x]) and
      "non-allophonic" ([c-f], [x-f]) continua after front and back vowels. Vowel
      affected German responses to [c-x] and [c-f], but not [x-f]. Vowel affected
      English responses to all continua. The asymmetric effect on German responses is
      explained as a perceptual expectation of [c] after [y]. The effect on English
      responses is explained by acoustic misparsing, which causes some of the vowel's
      spectrum to cue a spectrally similar fricative. 

PMID- 24907847
TI  - Passive ultrasonics using sub-Nyquist sampling of high-frequency thermal
      mechanical noise.
AB  - Monolithic integration of capacitive micromachined ultrasonic transducer arrays
      with low noise complementary metal oxide semiconductor electronics minimizes
      interconnect parasitics thus allowing the measurement of thermal-mechanical (TM)
      noise. This enables passive ultrasonics based on cross-correlations of diffuse TM
      noise to extract coherent ultrasonic waves propagating between receivers.
      However, synchronous recording of high-frequency TM noise puts stringent
      requirements on the analog to digital converter's sampling rate. To alleviate
      this restriction, high-frequency TM noise cross-correlations (12-25 MHz) were
      estimated instead using compressed measurements of TM noise which could be
      digitized at a sampling frequency lower than the Nyquist frequency. 

PMID- 24907846
TI  - Temporal predictability enhances auditory detection.
AB  - Periodic stimuli are common in natural environments and are ecologically
      relevant, for example, footsteps and vocalizations. This study reports a
      detectability enhancement for temporally cued, periodic sequences. Target noise
      bursts (embedded in background noise) arriving at the time points which followed
      on from an introductory, periodic "cue" sequence were more easily detected (by
      ~1.5 dB SNR) than identical noise bursts which randomly deviated from the cued
      temporal pattern. Temporal predictability and corresponding neuronal
      "entrainment" have been widely theorized to underlie important processes in
      auditory scene analysis and to confer perceptual advantage. This is the first
      study in the auditory domain to clearly demonstrate a perceptual enhancement of
      temporally predictable, near-threshold stimuli. 

PMID- 24907849
TI  - Mutations in zinc finger 407 [ZNF407] cause a unique autosomal recessive
      cognitive impairment syndrome.
AB  - BACKGROUND: A consanguineous Arab family is affected by an apparently novel
      autosomal recessive disorder characterized by cognitive impairment, failure-to
      thrive, hypotonia and dysmorphic features including bilateral ptosis and
      epicanthic folds, synophrys, midface hypoplasia, downturned mouth corners, thin
      upper vermillion border and prominent ears, bilateral 5th finger camptodactyly,
      bilateral short 4th metatarsal bones, and limited knee mobility bilaterally.
      METHODS: The family was studied by homozygosity mapping, candidate gene mutation
      screening and whole Exome Next Generation Sequencing of a single affected member
      to identify the offending gene and mutation. The mutated gene product was studied
      by structural bioinformatics methods. RESULTS: A damaging c.C5054G mutation
      affecting an evolutionary highly conserved amino acid p.S1685W was identified in
      the ZNF407 gene at 18q23. The Serine to Tryptophane mutation affects two of the
      three ZNF407 isoforms and is located in the last third of the protein, in a
      linker peptide adjoining two zinc-finger domains. Structural analyses of this
      mutation shows disruption of an H-bond that locks the relative spatial position
      of the two fingers, leading to a higher flexibility of the linker and thus to a
      decreased probability of binding to the target DNA sequence essentially
      eliminating the functionality of downstream domains and interfering with the
      expression of various genes under ZNF407 control during fetal brain development.
      CONCLUSIONS: ZNF407 is a transcription factor with an essential role in brain
      development. When specific and limited in number homozygosity intervals exist
      that harbor the offending gene in consanguineous families, Whole Exome Sequencing
      of a single affected individual is an efficient approach to gene mapping and
      mutation identification.

PMID- 24907848
TI  - Eating disorders among patients incarcerated only for repeated shoplifting: a
      retrospective quasi-case-control study in a medical prison in Japan.
AB  - BACKGROUND: Shoplifting is a serious problem among patients with eating
      disorders. For more than a decade, we have treated many patients with eating
      disorders incarcerated in Hachioji Medical Prison only for repeated shoplifting.
      METHODS: We analyzed the prison records and medical records of female psychiatric
      patients transferred to Hachioji Medical Prison between 2002 and 2011. Based on
      the offense listed at the time of sentencing, we extracted a shoplifting group
      and a drug-offense group from among all patients with eating disorders. One
      patient from the former group who had used substances and two from the latter
      group who had never shoplifted were excluded from the study. The groups had 41
      and 14 patients, respectively. A control group comprised patients with other
      mental disorders (n = 34). We compared eating disorder histories and subtypes,
      weight changes, comorbidities, life histories, past behavioral problems, and
      clinical behavioral problems among the three groups. RESULTS: The shoplifting
      group exhibited less impulsive behavior, substance abuse, antisocial features,
      borderline personality disorder, and past bulimia than did the drug-offense and
      control groups. The shoplifting group had higher educational achievement and
      steadier employment; however, their eating disorder histories and interpersonal
      dysfunction were more severe, and they had a higher psychiatric treatment dropout
      rate. There were also significant relationships with low body weight, anorexia
      nervosa-restricting type, obsessive-compulsive behaviors, and obsessive
      compulsive personality disorder in the shoplifting group. During the clinical
      course, food refusal, excessive exercise, food hoarding, and falsification of
      dietary intake amounts were more frequently observed in the shoplifting group.
      Conversely, drug requests and occurrences of self-harm were less frequent in the
      shoplifting group than in the drug-offense group. CONCLUSIONS: Although these
      results may be associated with specific characteristics of patients with eating
      disorders in the medical prison setting, we concluded that the repeated
      shoplifting by these patients is unrelated to antisocial or impulsive
      characteristics but is deeply rooted in these patients' severe and undertreated
      eating disorder psychopathology. Strong supportive treatment should be considered
      for patients with eating disorders who develop shoplifting behaviors. Further
      research is required to elucidate the mechanisms responsible for the relationship
      between shoplifting and eating disorders.

PMID- 24907852
TI  - Community-onset bacteraemia of unknown origin: clinical characteristics,
      epidemiology and outcome.
AB  - Bacteraemia of unknown origin is prevalent and has a high mortality rate.
      However, there are no recent reports focusing on this issue. From 2005 to 2011,
      all episodes of community onset bacteraemia of unknown origin (CO-BSI), diagnosed
      at a 700-bed university hospital were prospectively included. Risk factors for
      Enterobactericeae resistant to third-generation cephalosporins (3GCR-E),
      Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus spp, and
      predictors of mortality were assessed by logistic regression. Out of 4,598
      consecutive episodes of CO-BSI, 745 (16.2 %) were of unknown origin. Risk factors
      for S. aureus were male gender (OR 2.26; 1.33-3.83), diabetes mellitus (OR 1.71;
      1.01-2.91) and intravenous drug addiction (OR 17.24; 1.47-202); for P. aeruginosa
      were male gender (OR 2.19; 1.10-4.37) and health-care associated origin (OR 9.13;
      3.23-25.83); for 3GCR-E was recent antibiotic exposure (OR 2.53; 1.47-4.35),
      while for enterococci, it was recent hospital admission (OR 3.02; 1.64-5.55).
      Seven and 30-day mortality were 8.1 % and 13.4 %, respectively. Age over 65 years
      (OR 2.13; 1.28-3.55), an ultimately or rapidly fatal underlying disease (OR 4.15;
      2.23-7.60), bone marrow transplantation (OR 4.07; 1.24-13.31), absence of fever
      (OR 4.45; 2.25-8.81), shock on presentation (OR 10.48; 6.05-18.15) and isolation
      of S. aureus (OR 2.01; 1.00-4.04) were independently associated with mortality.
      In patients with bacteraemia of unknown origin, a limited number of clinical
      characteristics may be useful to predict its aetiology and to choose the
      appropriate empirical treatment. Although no modifiable prognostic factors have
      been found, management optimization of S. aureus should be considered a priority
      in this setting.

PMID- 24907853
TI  - Bacterial growth and wound infection following saphenous vein harvesting in
      cardiac surgery: a randomized controlled trial of the impact of microbial skin
      sealant.
AB  - The aim of the present study was to compare microbial skin sealant versus bare
      skin on the leg regarding intraoperative bacterial presence in the surgical wound
      and time to recolonization of the adjacent skin at the saphenous vein harvesting
      site. A second aim was to evaluate the incidence of leg wound infection 2 months
      after surgery. In this randomized controlled trial, 140 patients undergoing
      coronary artery bypass grafting (CABG) between May 2010 and October 2011 were
      enrolled. Bacterial samples were taken preoperatively and intraoperatively at
      multiple time points and locations. OF the patients, 125 (92.6 %) were followed
      up 2 months postoperatively regarding wound infection. Intraoperative bacterial
      growth did not differ between the bare skin (n = 68) and the microbial skin
      sealant group (n = 67) at any time point. At 2 months postoperatively, 7/61
      patients (11.5 %) in the skin sealant versus 14/64 (21.9 %) in the bare skin
      group (p = 0.120) had been treated with antibiotics for a verified or suspected
      surgical site infection (SSI) at the harvest site. We found almost no
      intraoperative bacterial presence on the skin or in the subcutaneous tissue,
      irrespective of microbial skin sealant use. In contrast, we observed a relatively
      high incidence of late wound infection, indicating that wound contamination
      occurred postoperatively. Further research is necessary to determine whether the
      use of microbial skin sealant reduces the incidence of leg wound infection at the
      saphenous vein harvest site.

PMID- 24907851
TI  - The cell-cell junctions of mammalian testes: I. The adhering junctions of the
      seminiferous epithelium represent special differentiation structures.
AB  - The seminiferous tubules and the excurrent ducts of the mammalian testis are
      physiologically separated from the mesenchymal tissues and the blood and lymph
      system by a special structural barrier to paracellular translocations of
      molecules and particles: the "blood-testis barrier", formed by junctions
      connecting Sertoli cells with each other and with spermatogonial cells. In
      combined biochemical as well as light and electron microscopical studies we
      systematically determine the molecules located in the adhering junctions of adult
      mammalian (human, bovine, porcine, murine, i.e., rat and mouse) testis. We show
      that the seminiferous epithelium does not contain desmosomes, or "desmosome-like"
      junctions, nor any of the desmosome-specific marker molecules and that the
      adhering junctions of tubules and ductules are fundamentally different. While the
      ductules contain classical epithelial cell layers with E-cadherin-based adherens
      junctions (AJs) and typical desmosomes, the Sertoli cells of the tubules lack
      desmosomes and "desmosome-like" junctions but are connected by morphologically
      different forms of AJs. These junctions are based on N-cadherin anchored in
      cytoplasmic plaques, which in some subforms appear thick and dense but in other
      subforms contain only scarce and loosely arranged plaque structures formed by
      alpha- and beta-catenin, proteins p120, p0071 and plakoglobin, together with a
      member of the striatin family and also, in rodents, the proteins ZO-1 and myozap.
      These N-cadherin-based AJs also include two novel types of junctions: the "areae
      adhaerentes", i.e., variously-sized, often very large cell-cell contacts and
      small sieve-plate-like AJs perforated by cytoplasm-to-cytoplasm channels of 5-7
      nm internal diameter ("cribelliform junctions"). We emphasize the unique
      character of this epithelium that totally lacks major epithelial marker molecules
      and structures such as keratin filaments and desmosomal elements as well as EpCAM
      and PERP-containing junctions. We also discuss the nature, development and
      possible functions of these junctions. 

PMID- 24907855
TI  - Diagnostic performance of apparent diffusion coefficient and quantitative kinetic
      parameters for predicting additional malignancy in patients with newly diagnosed
      breast cancer.
AB  - PURPOSE: To evaluate the diagnostic performance of an apparent diffusion
      coefficient (ADC) and quantitative kinetic parameters in patients with newly
      diagnosed breast cancer. MATERIALS AND METHODS: We enrolled 169 lesions in 89
      patients with breast cancer who underwent dynamic contrast-enhanced MRI (DCE-MRI)
      and diffusion-weighted imaging (DWI). Comparisons between benign and malignant
      lesions were performed for lesion type (mass or nonmass-like enhancement), size
      (>=1cm or<1cm), ADC, kinetic parameters and the presence of a US correlate.
      RESULTS: There were 63 benign and 106 malignant lesions. The mean size and
      initial peak enhancement of the benign lesions were significantly lower than
      those of malignant lesions (P<0.001 for both). The ADC of the benign lesions was
      significantly higher than that of malignant lesions (1.42*10(-3)mm(2)/sec vs.
      1.04*10(-3)mm(2)/sec; P<0.001). The area under the receiver operating
      characteristic curve (AUC) for predicting malignancy was 0.87 for the combined
      parameters of size, ADC, and initial peak enhancement, which was higher than
      those of each parameter. CONCLUSIONS: Combination of quantitative kinetic
      parameters and ADC showed higher diagnostic performance for predicting malignancy
      than each parameter alone for the evaluation of patients with breast cancer.

PMID- 24907854
TI  - The feasibility of assessing branched-chain amino acid metabolism in cellular
      models of prostate cancer with hyperpolarized [1-(13)C]-ketoisocaproate.
AB  - Recent advancements in the field of hyperpolarized (13)C magnetic resonance
      spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis
      of metabolic pathways. These non-invasive methods have increasingly shown
      application in impacting disease diagnosis and have further been employed in
      mechanistic studies of disease onset and progression. Our goals were to
      investigate branched-chain aminotransferase (BCAT) activity in prostate cancer
      with a novel molecular probe, hyperpolarized [1-(13)C]-2-ketoisocaproate ([1
      (13)C]-KIC), and explore the potential of branched-chain amino acid (BCAA)
      metabolism to serve as a biomarker. Using traditional spectrophotometric assays,
      BCAT enzymatic activities were determined in vitro for various sources of
      prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP)
      mouse and human cell lines). These preliminary studies indicated that low levels
      of BCAT activity were present in all models of prostate cancer but enzymatic
      levels are altered significantly in prostate cancer relative to healthy tissue.
      The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU
      145) that exhibited levels of BCAA metabolism comparable to the human disease
      state. Hyperpolarized [1-(13)C]-KIC was administered to prostate cancer cell
      lines, and the conversion of [1-(13)C]-KIC to the metabolic product, [1-(13)C]
      leucine ([1-(13)C]-Leu), could be monitored via hyperpolarized (13)C MRS. 

PMID- 24907850
TI  - Mechanisms of stress, energy homeostasis and insulin resistance in European
      adolescents--the HELENA study.
AB  - BACKGROUND AND AIMS: Stress is hypothesized to facilitate the development of
      obesity, whose the foundations are already set during childhood and adolescence.
      We investigated the relationship between the stress-system, selected mechanisms
      of energy homeostasis and insulin resistance (IR) in a sample of European
      adolescents. METHODS AND RESULTS: Within HELENA-CSS, 723 adolescents (12.5-17.5
      years) from 10 European cities provided all the necessary data for this study.
      Fasting blood samples were collected for cortisol, leptin, insulin and glucose
      analysis. HOMA-IR was calculated from insulin and glucose concentrations.
      Adolescents' body fat (BF) %, age and duration of exclusive breastfeeding were
      assessed. For boys and girls separately, the relationship of cortisol with
      leptin, insulin, glucose and HOMA-IR was examined by computing Pearson
      correlation coefficients and Hierarchical Linear Models (HLMs), with 'city' as
      cluster unit, adjusting for age, BF% and duration of exclusive breastfeeding. In
      boys, Pearson correlation coefficients illustrated positive correlations of
      cortisol with insulin (r = 0.144; p = 0.013), glucose (r = 0.315; p < 0.001) and
      HOMA-IR (r = 0.180; p = 0.002), whilst in girls, this positive relationship was
      observed for leptin (r = 0.147; p = 0.002), insulin (r = 0.095; p = 0.050) and
      HOMA-IR (r = 0.099; p = 0.041), but not for glucose (r = 0.054; p = 0.265).
      Observed associations were independent of adolescents' age, BF% and duration of
      exclusive breastfeeding after computing HLMs. CONCLUSION: This study suggests
      that the stress-system is positively related to mechanisms of energy homeostasis
      and IR in European adolescents, and reveals a potential small gender difference
      in this relationship. The hypothesis that stress might facilitate the development
      of obesity during adolescence is supported.

PMID- 24907856
TI  - Effects of urbanization on mercury deposition and accumulation in New England.
AB  - We compare total mercury (HgT) loading and methylmercury (MeHg) accumulation in
      streams and lakes from an urbanized area (Boston, Massachusetts) to rural regions
      of southern New Hampshire and Maine. The maximum HgT loading, as indicated by HgT
      atmospheric deposition, HgT emissions, and sediment HgT concentrations, did not
      coincide with maximum MeHg concentrations in fish. Urbanized ecosystems were
      areas of high HgT loading but had low MeHg concentrations in fish. Controls on
      MeHg production and accumulation appeared to be related primarily to HgT loading
      in undeveloped areas, while ecosystem sensitivity to MeHg formation appeared to
      be more important in regulating accumulation of MeHg in the urban area. 

PMID- 24907857
TI  - Effects of storage temperature and duration on release of antimony and bisphenol
      A from polyethylene terephthalate drinking water bottles of China.
AB  - We investigated effects of storage temperature and duration on release of
      antimony (Sb) and bisphenol A (BPA) from 16 brands of polyethylene terephthalate
      (PET) drinking water bottles in China. After 1-week storage, Sb release increased
      from 1.88-8.32 ng/L at 4  degrees C, to 2.10-18.4 ng/L at 25  degrees C and to
      20.3-2604 ng/L at 70  degrees C. The corresponding releases for BPA were less at
      0.26-18.7, 0.62-22.6, and 2.89-38.9 ng/L. Both Sb and BPA release increased with
      storage duration up to 4-week, but their releasing rates decreased with storage
      time, indicating that Sb and BPA release from PET bottles may become stable under
      long term storage. Human health risk was evaluated based on the worst case, i.e.,
      storage at 70  degrees C for 4-week. Chronic daily intake (CDI) caused by BPA
      release was below USEPA regulation, Sb release in one brand exceeded USEPA
      regulated CDI (400 ng/kg bw/d) with values of 409 and 1430 ng/kg bw/d for adult
      and children. 

PMID- 24907858
TI  - Organochlorine pesticides in bird species and their prey (fish) from the
      Ethiopian Rift Valley region, Ethiopia.
AB  - Organochlorine pesticides (OCPs) and stable isotopes were measured in muscle from
      4 bird and 5 fish species from the Ethiopian Rift Valley region where DDT is used
      for malaria control and vast agricultural activities are carried out. We
      investigated the bioaccumulation of OCPs such as DDTs, HCHs, chlordanes, and
      heptachlors between the species, and examined the potential risk posed by these
      compounds for bird species. Significant differences in contaminant profiles and
      levels were observed within the species. Levels of total OCPs ranged from 3.7 to
      148.7 MUg/g lipid in bird and 0.04 to 10.9 MUg/g lipid in fish species. DDTs were
      the predominant contaminant, and a positive relationship between delta(15)N and
      SigmaDDT concentrations was found. The main DDT metabolite, p,p'-DDE was the most
      abundant and significantly greater concentrations in bird species (up to 138.5
      MUg/g lipid), which could have deleterious effects on survival and/or
      reproduction of birds. 

PMID- 24907859
TI  - Oculomotor control as a biobehavioral indicator of impaired response inhibition
      in children with fetal alcohol spectrum disorders.

PMID- 24907860
TI  - Clinical results of implant placement in resorbed ridges using simultaneous
      guided bone regeneration: a multicenter case series.
AB  - OBJECTIVES: The purpose of this case series was to evaluate the new bone
      formation following guided bone regeneration (GBR) with a calcium phosphosilicate
      (CPS), alloplastic bone putty at peri-implant dehiscence defects and to assess
      survival rate of implants placed in the augmented sites after 12 months of
      function. MATERIALS AND METHODS: Implants were placed in patients exhibiting
      Seibert class I ridge defects resulting in peri-implant dehiscence defects. The
      defects were treated following GBR principles with the use of a CPS alloplastic
      bone graft putty in combination either with a collagen membrane or a titanium
      mesh. The height of each bony dehiscence was clinically measured at the time of
      implant placement and again during second-stage surgery. The percentage of
      complete defect coverage, frequency of adverse events, and risk factors for
      residual defect were determined. RESULTS: Thirty-six implants were placed in 26
      patients. Twenty-seven of the 36 sites employed a collagen membrane in
      conjunction with the CPS while the remaining nine sites utilized a titanium
      membrane. Mean gain in bone height was 3.23 +/- 2.04 mm, with 75 % of the peri
      implant defects achieving complete regeneration. A negative correlation was
      identified between patient age and complete coverage of the peri-implant defect
      (p = 0.026). The implant survival rate at 12 months was 97.22 %. CONCLUSION: Use
      of CPS bone putty during delayed implant placement at peri-implant dehiscence
      sites either in combination with a collagen membrane or a titanium mesh results
      in predictable defect coverage. CLINICAL RELEVANCE: The handling characteristics
      of CPS putty may simplify GBR protocol. Implants placed in conjunction with GBR
      have a very good survival rate after 1 year of follow-up.

PMID- 24907861
TI  - [Targetoid hemosiderotic hemangioma].

PMID- 24907862
TI  - [Quaternary prevention: containment as an ethical necessity].
AB  - The growing capacity of medicine to generate more iatrogenic events than ever,
      and the risk of unsustainability of health systems have led to new prevention
      concept: quaternary prevention aimed at restraining medicalization. Quaternary
      prevention is essential in the phenomenon called disease mongering, which could
      be translated as commercialization of disease. Encouraging this sort of
      prevention and halting the consequences of disease mongering requires the
      development of all the institutional potential for prevention, as well as all the
      personal willingness for restraint; it involves separating us from the
      unnecessary auspices of industry, being critical of our work, not being
      maleficent, respecting the principle of justice as managers of the limited public
      resources and making ourselves feel responsible for the social cost resulting
      from medical decisions. From this point of view, this work analyses neonatal
      screening, developments in the area of neonatology and primary health care. 

PMID- 24907864
TI  - [Sedation in term or near-term newborns with hypoxic-ischemic encephalopathy who
      require therapeutic hypothermia].

PMID- 24907865
TI  - Penile paraffinoma.

PMID- 24907866
TI  - Use of visual and permanent identification for pets by veterinary clinics.
AB  - It is estimated that more than 5 million stray dogs and cats enter animal
      shelters in the USA each year, but less than half are ever reunited with their
      owners. Lost pets with identification microchips are up to 21 times more likely
      to be reunited than those without. Finders of lost pets are more likely to
      consult veterinarians than shelters for assistance, and pet owners look first to
      veterinarians for advice regarding pet health, protection, and welfare. An online
      survey of 1086 veterinary clinics in the South-Eastern USA was conducted to
      evaluate how veterinary clinics functioned as a part of the pet identification
      network. Scanning and microchip implants were offered by 91% of surveyed clinics
      and 41% used 'global' scanners capable of detecting all currently used microchip
      brands. Clinics more frequently relied on pet owners to register contact
      information rather than providing this service for clients (52% vs. 43%,
      respectively). Even though lost dogs are more likely to be reunited with owners
      than lost cats, microchips and collars were more likely to be recommended for all
      dogs (85% and 93%, respectively) than for all cats (67% and 61%, respectively).
      Only half of clinics that recommended identification collars made them available
      to their clients. Veterinarians can protect animals, pet owners and the human
      animal bond by integrating pet identification into preventive health care.

PMID- 24907863
TI  - [Thromboprophylaxis in critically ill children in Spain and Portugal].
AB  - INTRODUCTION: Although critically ill children may be at risk from developing
      deep venous thrombosis (DVT), data on its incidence and effectiveness of
      thromboprophylaxis are lacking. OBJECTIVE: To describe the use of
      thromboprophylaxis in critically ill children in Spain and Portugal, and to
      compare the results with international data. MATERIAL AND METHODS: Secondary
      analysis of the multinational study PROTRACT, carried out in 59 PICUs from 7
      developed countries (4 from Portugal and 6 in Spain). Data were collected from
      patients less than 18 years old, who did not receive therapeutic
      thromboprophylaxis. RESULTS: A total of 308 patients in Spanish and Portuguese
      (Iberian) PICUS were compared with 2176 admitted to international PICUs. Risk
      factors such as femoral vein (P=.01), jugular vein central catheter (P<.001),
      cancer (P=.03), and sepsis (P<.001), were more frequent in Iberian PICUs. The
      percentage of patients with pharmacological thromboprophylaxis was similar in
      both groups (15.3% vs. 12.0%). Low molecular weight heparin was used more
      frequently in Iberian patients (P<.001). In treated children, prior history of
      thrombosis (P=.02), femoral vein catheter (P<.001), cancer (P=.02) and cranial
      trauma or craniectomy (P=.006), were more frequent in Iberian PICUs. Mechanical
      thromboprophylaxis was used in only 6.8% of candidates in Iberian PICUs, compared
      with 23.8% in the international PICUs (P<.001). CONCLUSIONS: Despite the presence
      of risk factors for DVT in many patients, thromboprophylaxis is rarely
      prescribed, with low molecular weight heparin being the most used drug. Passive
      thromboprophylaxis use is anecdotal. There should be a consensus on guidelines of
      thromboprophylaxis in critically ill children.

PMID- 24907867
TI  - Fecal and urinary N-methylhistamine concentrations in dogs with chronic
      gastrointestinal disease.
AB  - Due to their ability to release inflammatory mediators, such as histamine, mast
      cells are potentially important in gastrointestinal disease. The purpose of this
      study was to measure N-methylhistamine (NMH), a histamine metabolite, in fecal
      and urine samples from dogs with chronic gastrointestinal disease. Fecal and
      urinary NMH concentrations were compared between dogs with chronic
      gastrointestinal disease and control dogs, and/or to control ranges. Correlation
      between fecal and urinary NMH concentrations, serum C-reactive protein (CRP)
      concentration, the clinical disease activity index (CCECAI), and gastrointestinal
      mucosal mast cell numbers (where available) in dogs with gastrointestinal disease
      was evaluated. Seven of 16 dogs with gastrointestinal disease had increased
      urinary or fecal NMH concentrations, but there was no correlation between NMH
      concentrations and the CCECAI or mucosal mast cells numbers. Urinary NMH
      concentrations were positively associated with histological grading and serum CRP
      concentrations. The lack of correlation between NMH concentrations and the CCECAI
      suggests that NMH may not be a good marker for clinical disease activity in dogs
      as determined by the CCECAI. Based on their association with severity of
      intestinal mucosal inflammation, urinary NMH concentrations may potentially have
      clinical utility as a marker of intestinal inflammation in certain groups of dogs
      with chronic gastrointestinal disease, but future studies in a larger number of
      dogs are necessary to further characterize the role of mast cell-mediated
      inflammation in dogs with chronic gastrointestinal disease.

PMID- 24907868
TI  - HIV infection: epidemiology, pathogenesis, treatment, and prevention.
AB  - HIV prevalence is increasing worldwide because people on antiretroviral therapy
      are living longer, although new infections decreased from 3.3 million in 2002, to
      2.3 million in 2012. Global AIDS-related deaths peaked at 2.3 million in 2005,
      and decreased to 1.6 million by 2012. An estimated 9.7 million people in low
      income and middle-income countries had started antiretroviral therapy by 2012.
      New insights into the mechanisms of latent infection and the importance of
      reservoirs of infection might eventually lead to a cure. The role of immune
      activation in the pathogenesis of non-AIDS clinical events (major causes of
      morbidity and mortality in people on antiretroviral therapy) is receiving
      increased recognition. Breakthroughs in the prevention of HIV important to public
      health include male medical circumcision, antiretrovirals to prevent mother-to
      child transmission, antiretroviral therapy in people with HIV to prevent
      transmission, and antiretrovirals for pre-exposure prophylaxis. Research into
      other prevention interventions, notably vaccines and vaginal microbicides, is in
      progress.

PMID- 24907869
TI  - Cell-specific and endothelium-dependent regulations of matrix metalloproteinase-2
      in rat aorta.
AB  - Chronic activation of angiotensin II (ANGII) and matrix metalloproteinase-2 (MMP
      2) during hypertension contributes to increased aortic stiffness. We studied
      signalling mechanisms employed by ANGII in the regulation of latent (pro-) and
      active forms of MMP-2 in rat aortic endothelial and smooth muscle cells, along
      with isolated rat aorta. Using western blotting, we demonstrate that ANGII (1
      umol/L) significantly (P < 0.01) increases pro-MMP-2 protein expression after 8 h
      not only in endothelial and smooth muscle cells, but also in isolated rat aorta.
      We demonstrate that ANGII acts via AT1 receptor-activated cell-specific pathways.
      In endothelial cells, the JNK1/c-jun pathway is activated, whereas in smooth
      muscle cells, the JAK2/STAT3 pathway. Activation of JAK2/STAT3 pathway in
      response to ANGII was EGF receptor-dependent. Results obtained in cell culture
      are in agreement with the results obtained in isolated aorta. However, active MMP
      2 was not found under cell culture conditions, whereas in isolated aorta, active
      MMP-2 was significantly (P < 0.05) increased after stimulation with ANGII, as
      detected by gelatine zymography. This increase of MMP-2 activity was not
      inhibited by blocking the pathways we identified to control pro-MMP-2 protein
      expression, but was abolished in the absence of endothelium. Our findings
      demonstrate that ANGII regulates pro-MMP-2 protein expression via cell-specific
      pathways in rat aorta. The endothelium may play an essential role in the
      activation of pro-MMP-2. These results may lead to new strategies for inhibiting
      MMP-2 expression and activity in distinct cell types of the aortic wall.

PMID- 24907870
TI  - Soluble guanylyl cyclase activation improves progressive cardiac remodeling and
      failure after myocardial infarction. Cardioprotection over ACE inhibition.
AB  - Impaired nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signaling is
      involved in the pathogenesis of ischemic heart diseases, yet the impact of long
      term sGC activation on progressive cardiac remodeling and heart failure after
      myocardial infarction (MI) has not been explored. Moreover, it is unknown whether
      stimulating the NO/heme-independent sGC provides additional benefits to ACE
      inhibition in chronic ischemic heart failure. Starting 10 days after MI, rats
      were treated with placebo, the sGC activator ataciguat (10 mg/kg/twice daily),
      ramipril (1 mg/kg/day), or a combination of both for 9 weeks. Long-term ataciguat
      therapy reduced left ventricular (LV) diastolic filling pressure and pulmonary
      edema, improved the rightward shift of the pressure-volume curve, LV contractile
      function and diastolic stiffness, without lowering blood pressure. NO/heme
      independent sGC activation provided protection over ACE inhibition against
      mitochondrial superoxide production and progressive fibrotic remodeling,
      ultimately leading to a further improvement of cardiac performance, hypertrophic
      growth and heart failure. We found that ataciguat stimulating sGC activity was
      potentiated in (myo)fibroblasts during hypoxia-induced oxidative stress and that
      NO/heme-independent sGC activation modulated fibroblast-cardiomyocyte crosstalk
      in the context of heart failure and hypoxia. In addition, ataciguat inhibited
      human cardiac fibroblast differentiation and extracellular matrix protein
      production in response to TGF-beta1. Overall, long-term sGC activation targeting
      extracellular matrix homeostasis conferred cardioprotection against progressive
      cardiac dysfunction, pathological remodeling and heart failure after myocardial
      infarction. NO/heme-independent sGC activation may prove to be a useful
      therapeutic target in patients with chronic heart failure and ongoing fibrotic
      remodeling.

PMID- 24907871
TI  - Randomized, controlled trial comparing the effects of anesthesia with propofol,
      isoflurane, desflurane and sevoflurane on pain after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Pain is the primary complaint and the main reason for prolonged
      recovery after laparoscopic cholecystectomy. The authors hypothesized that
      patients undergoing laparoscopic cholecystectomy will have less pain four hours
      after surgery when receiving maintenance of anesthesia with propofol when
      compared to isoflurane, desflurane, or sevoflurane. METHODS: In this prospective,
      randomized trial, 80 patients scheduled for laparoscopic cholecystectomy were
      assigned to propofol, isoflurane, desflurane, or sevoflurane for the maintenance
      of anesthesia. Our primary outcome was pain measured on the numeric analog scale
      four hours after surgery. We also recorded intraoperative use of opioids as well
      as analgesic consumption during the first 24h after surgery. RESULTS: There was
      no statistically significant difference in pain scores four hours after surgery
      (p=0.72). There were also no statistically significant differences in pain scores
      between treatment groups during the 24h after surgery (p=0.45). Intraoperative
      use of fentanyl and morphine did not vary significantly among the groups (p=0.21
      and 0.24, respectively). There were no differences in total morphine and
      hydrocodone/APAP use during the first 24h (p=0.61 and 0.53, respectively).
      CONCLUSION: Patients receiving maintenance of general anesthesia with propofol do
      not have less pain after laparoscopic cholecystectomy when compared to
      isoflurane, desflurane, or sevoflurane.

PMID- 24907872
TI  - Comparison of the effects of dexmedetomidine administered at two different times
      on renal ischemia/reperfusion injury in rats.
AB  - BACKGROUND AND OBJECTIVES: We investigated the effect of dexmedetomidine on
      ischemic renal failure in rats. METHODS: In the present study, 26 male adult
      Wistar albino rats weighting 230-300 g were randomly separated into four groups:
      sham-operated (n=5), ischemia reperfusion (IR) (IR group, n=7), IR/reperfusion
      treatment with dexmedetomidine (Dex. R group, n=7) and IR/pre-ischemic treatment
      with dexmedetomidine (Dex. I group, n=7). In the first group, sham operation was
      achieved and renal clamps were not applied. For the IR group, renal ischemia was
      induced by occlusion of the bilateral renal arteries and veins for 60 min
      followed by reperfusion for 24h. For the Dex. R and Dex. I groups, the same
      surgical procedure as in the IR group was performed, and dexmedetomidine (100
      mcg/kg intraperitoneal) was administrated at the 5th min after reperfusion and
      before ischemia. At the end of reperfusion, blood samples were drawn, the rats
      were sacrificed, and the left kidney was processed for histopathology. RESULTS:
      The blood urea nitrogen (BUN) levels in groups Dex. R and Dex. I were
      significantly lower than in the IR group (p=0.015, p=0.043), although urine flow
      was significantly higher in group Dex. R (p=0.003). The renal histopathological
      score in the IR group was significantly higher than in the other groups. There
      was no significant difference between the Dex. R and Dex. I groups. CONCLUSIONS:
      The results were shown that administration of dexmedetomidine reduced the renal
      IR injury histomorphologically. Administration of dexmedetomidine in the
      reperfusion period was considered as more effective due to increase in urinary
      output and decrease in BUN levels.

PMID- 24907874
TI  - Oxygen concentrators performance with nitrous oxide at 50:50 volume.
AB  - BACKGROUND AND OBJECTIVES: Few investigations have addressed the safety of oxygen
      from concentrators for use in anesthesia in association with nitrous oxide. This
      study evaluated the percent of oxygen from a concentrator in association with
      nitrous oxide in a semi-closed rebreathing circuit. METHODS: Adult patients
      undergoing low risk surgery were randomly allocated into two groups, receiving a
      fresh gas flow of oxygen from concentrators (O293) or of oxygen from
      concentrators and nitrous oxide (O293N2O). The fraction of inspired oxygen and
      the percentage of oxygen from fresh gas flow were measured every 10 min. The
      ratio of FiO2/oxygen concentration delivered was compared at various time
      intervals and between the groups. RESULTS: Thirty patients were studied in each
      group. There was no difference in oxygen from concentrators over time for both
      groups, but there was a significant improvement in the FiO2 (p<0.001) for O293
      group while a significant decline (p<0.001) for O293N2O. The FiO2/oxygen ratio
      varied in both groups, reaching a plateau in the O293 group. Pulse oximetry did
      not fall below 98.5% in either group. CONCLUSION: The FiO2 in the mixture of O293
      and nitrous oxide fell during the observation period although oxygen saturation
      was higher than 98.5% throughout the study. Concentrators can be considered a
      stable source of oxygen for use during short anesthetic procedures, either pure
      or in association with nitrous oxide at 50:50 volume.

PMID- 24907873
TI  - Addition of lidocaine to levobupivacaine reduces intrathecal block duration:
      randomized controlled trial.
AB  - BACKGROUND: The duration of the spinal block is a concern for anesthetists. Low
      dose intrathecal lidocaine has vasodilatory effects and increases the local
      anesthetic clearance from the intrathecal space. The aim was to investigate
      whether this effect of lidocaine can be used to increase the resolution of
      levobupivacaine spinal anesthesia. METHOD: After obtaining ethical approval and
      informed patient consent, 40 patients underwent transurethral prostate resection
      were studied. Patients were randomized into two groups and patients received
      either levobupivacaine 6.75 mg + 0.3 mL 2% lidocaine (Group L) or levobupivacaine
      6.75 mg + saline (Group C). The main outcome measures were the difference between
      groups regarding the duration of the spinal block and PACU stay. Secondary
      outcome measures were the difference between groups in onset and resolution of
      the spinal block, adverse events and treatments were also investigated. RESULTS:
      Spinal block resolved faster in Group L than Group C; 162.43+/-39.4 min vs 219.73
      +/- 37.3 min (p = 0.000). PACU time was shorter in Group L (109 +/- 49.9 min in
      Group L vs 148 +/- 56.8 min in Group C) (p = 0.036). There was no difference
      between groups with respect to the incidence of adverse events and treatments.
      Groups were also similar regarding complications. PDPH and TNS were not observed
      in any group. CONCLUSION: Addition of low dose lidocaine to hyperbaric
      levobupivacaine reduces the duration of the intrathecal block provided by
      hyperbaric levobupivacaine. This technique can be used to reduce the spinal block
      duration for relatively short procedures like TUR-P.

PMID- 24907875
TI  - Ondansetron reducing pain on injection of etomidate: a controlled randomized
      study.
AB  - INTRODUCTION: Etomidate causes pain when injected intravenously. In this study we
      sought to determine if pretreatment by ondansetron reduces the pain on injection
      of etomidate. METHODS: In this randomized, double blinded, placebo-controlled
      clinical trial, 20 patients of both sexes aged between 18 and 50 years of
      American Society of Anesthesiologists (ASA) physical status class I or II, whom
      were candidates for various elective surgical procedures and need more than one
      intravenous access were enrolled in the study. On arrival to the operating room
      two 22 gauge cannulas were inserted into veins on the dorsum of both hands.
      Following the infusion of 100mL normal saline into both intravenous lines, using
      an elastic band, venous drainage of hands was occluded at midarm. The patients
      were administered 8 mg (2 mL) of ondansetron into one hand and 2 mL of 0.9%
      saline into the other hand at the same time. The elastic band was removed after 1
      min and 2mg (1 mL) of etomidate was administered at the same rate simultaneously
      into intravenous lines. The patients were asked to give a score of pain based on
      a verbal analog scale (VAS) to each hand. RESULTS: A total number of 20 patients
      were studied (male = 55%, female = 45%). The mean age of the participants was
      37.5 +/- 13.1 years old and the mean weight was 67.7 +/- 7.3 kg. The mean VAS for
      injection pain of etomidate after pre-administration of intravenous ondansetron
      was 1.5 +/- 1.2 which was lower compared to pre-administration of placebo (3.2 +/
      2.8, p < 0.05). CONCLUSION: This study illustrates that pre-treatment with
      intravenous ondansetron significantly reduces the pain on injection of etomidate.

PMID- 24907877
TI  - Efficiency of levobupivacaine and bupivacaine for supraclavicular block: a
      randomized double-blind comparative study.
AB  - BACKGROUND AND OBJECTIVES: Success rate of catheter applications is low in
      supraclavicular block. Thus, bupivacaine and levobupivacaine become important
      with their long effect time in single injection practices. In this study, we
      aimed to compare the effectiveness, side effects and complications of bupivacaine
      and levobupivacaine in supraclavicular block. METHODS: Sixty patients aged
      between 20 and 65, with body weight between 50 and 100 kg, in the ASA I-II-III
      group who were scheduled for hand, forearm and arm surgery using supraclavicular
      block were randomized into two groups of 30. The patients received 30 ml 0.5%
      bupivacaine (Group B) or 30 ml 0.5% levobupivacaine (Group L). Motor and sensory
      blocks were evaluated. Motor and sensory block onset times, total block
      durations, postoperative pain, amount of postoperative analgesic used and patient
      satisfaction were recorded. RESULTS: Demographic data, distribution of surgical
      area and hemodynamic data were similar between the two groups. Surgery, motor and
      sensory block durations of Group B and L patients did not vary statistically
      significantly. However, motor and sensory block onset times in Group B were
      significantly shorter than Group L (p<0.05). The mean time for first
      postoperative analgesic demand were 16.6 +/- 8.0 h in Group B and 14.4 +/- 7.3h
      in Group L (p>0.05). CONCLUSION: 30 ml 0.5% bupivacaine and levobupivacaine
      provide similar block characteristics for supraclavicular block. Bupivacaine
      leads to faster motor and sensory block onset compared to levobupivacaine however
      similar duration of postoperative analgesia.

PMID- 24907876
TI  - Comparison of the effects and complications of unilateral spinal anesthesia
      versus standard spinal anesthesia in lower-limb orthopedic surgery.
AB  - INTRODUCTION: A restricted sympathetic block during spinal anesthesia may
      minimize hemodynamic changes. This prospective randomized study compared
      unilateral and bilateral spinal anesthesia with respect to the intra- and
      postoperative advantages and complications of each technique. MATERIAL AND
      METHODS: Spinal anesthesia was induced with 0.5% hyperbaric bupivacaine and a 25
      G Quincke needle (Dr. J) in two groups of patients with physical status ASA I-II
      who had been admitted for orthopedic surgeries. In group A, dural puncture was
      performed with the patient in a seated position using 2.5 cm(3) of hyperbaric
      bupivacaine. Each patient was then placed in the supine position. In group B,
      dural puncture was performed with the patient in the lateral decubitus position
      with 1.5 cm(3) of hyperbaric bupivacaine. The lower limb was the target limb. The
      speed of injection was 1 mL/30s, and the duration of time spent in the lateral
      decubitus position was 20 min. RESULTS: The demographic data were similar in both
      groups. The time to the onset of the sensory and motor block was significantly
      shorter in group A (p=0.00). The duration of motor and sensory block was shorter
      in group B (p<0.05). The success rate for unilateral spinal anesthesia in group B
      was 94.45%. In two patients, the spinal block spread to the non-dependent side.
      The incidence of complications (nausea, headache, and hypotension) was lower in
      group B (p=0.02). CONCLUSION: When unilateral spinal anesthesia was performed
      using a low-dose, low-volume and low-flow injection technique, it provides
      adequate sensory-motor block and helps to achieve stable hemodynamic parameters
      during orthopedic surgery on a lower limb. Patients were more satisfied with this
      technique as opposed to the conventional approach. Furthermore, this technique
      avoids unnecessary paralysis on the non-operated side.

PMID- 24907878
TI  - Transfusional profile in different types of intensive care units.
AB  - BACKGROUND AND OBJECTIVES: anemia is a common clinical finding in intensive care
      units. The red blood cell transfusion is the main form of treatment, despite the
      associated risks. Thus, we proposed to evaluate the profile of transfusional
      patients in different intensive care units. METHODS: prospective analysis of
      patients admitted in the intensive care units of a tertiary university hospital
      with an indication for transfusion of packed red blood cells. Demographic profile
      and transfusional profile were collected, a univariate analysis was done, and the
      results were considered significant at p <= 0.05. RESULTS: 408 transfusions were
      analyzed in 71 patients. The mean hemoglobin concentration on admission was 9.7
      +/- 2.3g/dL and the pre-transfusional concentration was 6.9 +/- 1.1g/dL. The main
      indications for transfusion were hemoglobin concentration (49%) and active
      bleeding (32%). The median number of units transfused per episode was 2 (1-2) and
      the median storage time was 14 (7-21) days. The number of patients transfused
      with hemoglobin levels greater than 7 g/dL and the number of bags transfused per
      episode were significantly different among intensive care units. Patients who
      received three or more transfusions had longer mechanical ventilation time and
      intensive care unit stay and higher mortality after 60 days. There was an
      association of mortality with disease severity but not with transfusional
      characteristics. CONCLUSIONS: the practice of blood products transfusion was
      partially in agreement with the guidelines recommended, although there are
      differences in behavior between the different profiles of intensive care units.
      Transfused patients evolved with unfavorable outcomes. Despite the scarcity of
      blood in blood banks, the mean storage time of the bags was high.

PMID- 24907879
TI  - Preanesthetic assessment data do not influence the time for tracheal intubation
      with AirtraqTM video laryngoscope in obese patients.
AB  - PURPOSE: this study investigated the influence of anatomical predictors on
      difficult laryngoscopy and orotracheal intubation in obese patients by comparing
      Macintosh and AirtraqTM laryngoscopes. METHODS: from 132 bariatric surgery
      patients (body mass index >= 35 kgm(-1)), cervical perimeter, sternomental
      distance, interincisor distance, and Mallampati score were recorded. The patients
      were randomized into two groups according to whether a Macintosh (n=64) or an
      AirtraqTM (n=68) laryngoscope was used for tracheal intubation. Time required for
      intubation was the first outcome. Cormack-Lehane score, number of intubation
      attempts, the Macintosh blade used, any need for external tracheal compression or
      the use of gum elastic bougie were recorded. Intubation failure and strategies
      adopted were also registered. RESULTS: intubation failed in two patients in the
      Macintosh laryngoscope group, and these patients were included as worst cases
      scenario. The intubation times were 36.9+22.8s and 13.7+3.1s for the Macintosh
      and AirtraqTM laryngoscope groups (p<0.01), respectively. Cormack-Lehane scores
      were also lower for the AirtraqTM group. One patient in the Macintosh group with
      intubation failure was quickly intubated with the AirtraqTM. Cervical
      circumference (p<0.01) and interincisor distance (p<0.05) influenced the time
      required for intubation in the Macintosh group but not in the AirtraqTM group.
      CONCLUSION: in obese patients despite increased neck circumference and limited
      mouth opening, the AirtraqTM laryngoscope affords faster tracheal intubation than
      the Macintosh laryngoscope, and it may serve as an alternative when conventional
      laryngoscopy fails.

PMID- 24907880
TI  - Syndrome of inappropriate antidiuretic hormone secretion related to Guillain
      Barre syndrome after laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVES: Guillain-Barre Syndrome is one of the most common
      causes of acute polyneuropathy in adults. Recently, the occurrence of Guillain
      Barre Syndrome after major and minor surgical operations has been increasingly
      debated. In Guillain-Barre syndrome, syndrome of inappropriate antidiuretic
      hormone secretion and dysautonomy are generally observed after maximal motor
      deficit. CASE REPORT: A 44-year-old male patient underwent a laparoscopic
      cholecystectomy for acute cholecystitis. After the development of a severe
      headache, nausea, diplopia, and attacks of hypertension in the early
      postoperative period, a computer tomography of the brain was normal. Laboratory
      tests revealed hyponatremia linked to syndrome of inappropriate antidiuretic
      hormone secretion, the patient's fluids were restricted, and furosemide and 3%
      NaCl treatment was initiated. On the second day postoperative, the patient
      developed numbness moving upward from the hands and feet, loss of strength,
      difficulty swallowing and respiratory distress. Guillain-Barre syndrome was
      suspected, and the patient was moved to intensive care. Cerebrospinal fluid
      examination showed 320 mg/dL protein, and acute motor-sensorial axonal neuropathy
      was identified by electromyelography. Guillain-Barre syndrome was diagnosed, and
      intravenous immune globulin treatment (0.4 g/kg/day, 5 days) was initiated. After
      10 days in the intensive care unit, at which the respiratory, hemodynamic,
      neurologic and laboratory results returned to normal, the patient was transferred
      to the neurology service. CONCLUSIONS: Our case report indicates that although
      syndrome of inappropriate antidiuretic hormone secretion and autonomic
      dysfunction are rarely the initial characteristics of Guillain-Barre syndrome,
      the possibility of postoperative syndrome of inappropriate antidiuretic hormone
      secretion should be kept in mind. The presence of secondary hyponatremia in this
      type of clinical presentation may delay diagnosis.

PMID- 24907881
TI  - Inferior venacaval compression due to excessive abdominal packing.
AB  - Inferior venacaval compression is a common problem in late pregnancy. It can also
      occur due to compression of inferior venacava by abdominal or pelvic tumors. We
      report a case of acute iatrogenic inferior venacaval compression due to excessive
      abdominal packing during an intraabdominal surgery. 

PMID- 24907882
TI  - Anesthesia for a patient with Fanconi anemia for developmental dislocation of the
      hip: a case report.
AB  - Fanconi anemia is a rare autosomal recessive inherited bone marrow failure
      syndrome with congenital and hematological abnormalities. Literature regarding
      the anesthetic management in these patients is limited. A management of a
      developmental dislocation of the hip was described in a patient with fanconi
      anemia. Because of the heterogeneous nature, a patient with fanconi anemia should
      be established thorough preoperative evaluation in order to diagnose on clinical
      features. In conclusion, we preferred caudal anesthesia in this patient with
      fanconi anemia without thrombocytopenia, because of avoiding from N2O, reducing
      amount of anesthetic, existing microcephaly, hypothyroidism and elevated liver
      enzymes, providing postoperative analgesia, and reducing amount of analgesic used
      postoperatively. 

PMID- 24907883
TI  - Pacemakers and implantable cardioverter defibrillators--general and anesthetic
      considerations.
AB  - A pacemaking system consists of an impulse generator and lead or leads to carry
      the electrical impulse to the patient's heart. Pacemaker and implantable
      cardioverter defibrillator codes were made to describe the type of pacemaker or
      implantable cardioverter defibrillator implanted. Indications for pacing and
      implantable cardioverter defibrillator implantation were given by the American
      College of Cardiologists. Certain pacemakers have magnet-operated reed switches
      incorporated; however, magnet application can have serious adverse effects;
      hence, devices should be considered programmable unless known otherwise. When a
      device patient undergoes any procedure (with or without anesthesia), special
      precautions have to be observed including a focused history/physical examination,
      interrogation of pacemaker before and after the procedure, emergency
      drugs/temporary pacing and defibrillation, reprogramming of pacemaker and
      disabling certain pacemaker functions if required, monitoring of electrolyte and
      metabolic disturbance and avoiding certain drugs and equipments that can
      interfere with pacemaker function. If unanticipated device interactions are
      found, consider discontinuation of the procedure until the source of interference
      can be eliminated or managed and all corrective measures should be taken to
      ensure proper pacemaker function should be done. Post procedure, the cardiac rate
      and rhythm should be monitored continuously and emergency drugs and equipments
      should be kept ready and consultation with a cardiologist or a pacemaker
      implantable cardioverter defibrillator service may be necessary. 

PMID- 24907884
TI  - Thoracic epidural anesthesia in a geriatric patient with cardiac risk: a case
      report.

PMID- 24907885
TI  - Can positioning alter the success of endotracheal intubation in obese?

PMID- 24907886
TI  - Palatoplasty in a patient with Seckel syndrome: an anesthetic challenge.

PMID- 24907887
TI  - Comparative study between bupivacaine (S75-R25) and ropivacaine to evaluate
      cardiovascular safety in brachial plexus block: Hamaji A et al.: Rev Bras
      Anestesiol, 2013;63(4):322-326.

PMID- 24907889
TI  - Foreword to the special issue low-voltage electron microscopy.

PMID- 24907888
TI  - [The electrocardiogram in the paediatric age group].
AB  - A properly interpreted electrocardiogram (ECG) provides important information and
      is an inexpensive and easy test to perform. It continues to be the method of
      choice for the diagnosis of arrhythmias. Although the principles of cardiac
      electrophysiology are the same, there are anatomical and physiological age
      dependent changes which produce specific alterations in the paediatric ECG, and
      which may be misinterpreted as pathological. The intention of this article is to
      address in a systematic way the most relevant aspects of the paediatric ECG, to
      propose a possible reading scheme of the ECG and to review the electrocardiograph
      tracings most frequently found in the paediatric age group. 

PMID- 24907890
TI  - Discharge practices for the intensive care patient: a qualitative exploration in
      the general ward setting.
AB  - OBJECTIVE: To explore how registered nurses (RNs) in the general ward perceive
      discharge processes and practices for patients recently discharged from the
      intensive care unit (ICU). BACKGROUND: Patients discharged from the ICU
      environment often require complicated and multifaceted care. The ward-based RN is
      at the forefront of the care of this fragile patient population, yet their views
      and perceptions have seldom been explored. DESIGN: A qualitative grounded theory
      design was used to guide focus group interviews with the RN participants.
      METHODS: Five semi-structured focus group interviews, including 27 RN
      participants, were conducted in an Australian metropolitan tertiary referral
      hospital in 2011. Data analyses of transcripts, field notes and memos used
      concurrent data generation, constant comparative analysis and theoretical
      sampling. RESULTS: Results yielded a core category of 'two worlds' stressing the
      disconnectedness between ICU and the ward setting. This category was divided into
      sub categories of 'communication disconnect' and 'remember the family'.
      Properties of 'what we say', 'what we write', 'transfer' and 'information needs'
      respectively were developed within those sub-categories. CONCLUSION: The
      discharge process for patients within the ICU setting is complicated and largely
      underappreciated. There are fundamental, misunderstood differences in
      prioritisation and care of patients between the areas, with a deep understanding
      of practice requirements of ward based RNs not being understood. The findings of
      this research may be used to facilitate inter departmental communications and
      progress practice development.

PMID- 24907891
TI  - The destructive effects of antibiotics on the amniotic membrane ultrastructure.
AB  - The aim of the study was to examine the influence of different antibiotics on
      amniotic membrane epithelium and to observe the related ultrastructural changes
      using transmission electron microscope (TEM). Prospective comparative laboratory
      study. Amniotic membrane samples from a single placenta were obtained using a
      sterilized method. Tissue samples were placed in either saline or antibiotics
      containing (penicillin, streptomycin, neomycin, or amphotericin B) solutions. The
      viability of the amniotic membrane epithelial cells was then assessed for saline
      and antibiotics using both light microscope and TEM to investigate morphological
      changes. The ultrastructural examination of amniotic membrane epithelium held in
      antibiotics-containing solutions showed damage to the cell membrane, rarefaction,
      and loss of microvilli. Amniotic membrane from the control group showed intact
      epithelium, with surface microvilli and junctional complexes between the cells
      and the basal membrane. The destructive effects of antibiotics on freshly
      obtained amniotic membrane were examined with both light microscopy and
      transmission electron microscopy and significant differences in the
      ultrastructure were observed. 

PMID- 24907892
TI  - Linking community, parenting, and depressive symptom trajectories: testing
      resilience models of adolescent agency based on race/ethnicity and gender.
AB  - Family stress models illustrate how communities affect youth outcomes through
      effects on parents and studies consistently show the enduring effects of early
      community context. The present study takes a different approach identifying human
      agency during adolescence as a potentially significant promotive factor mediating
      the relationship between community, parenting, and mental health. While agency is
      an important part of resilience, its longitudinal effects are unknown,
      particularly based on gender and race/ethnicity. The purpose of this research was
      to model the long-term effects of community structural adversity and social
      resources as predictors of adolescent depressive symptom trajectories via
      indirect effects of parental happiness, parent-child relationships, and human
      agency. Latent growth analyses were conducted with 1,796 participants (53%
      female; 56% White) across four waves of the National Longitudinal Study of
      Adolescent Health spanning adolescence (Wave 1) through adulthood (Wave 4). The
      results identified agency as an important promotive factor during adolescence
      with long-term mental health benefits, but only for White and male participants.
      For these individuals, community social resources and the quality of the parent
      child relationship were related to higher levels of agency and more positive
      mental health trajectories. Although community social resources similarly
      benefitted parenting and agency among females and non-White participants, there
      were no significant links between agency and depressive symptoms for these youth.
      The results suggest that agency remains an important, but poorly understood
      concept and additional work is necessary to continue unpacking its meaning for
      diverse groups of youth.

PMID- 24907893
TI  - Community-aware user profile enrichment in folksonomy.
AB  - In the era of big data, collaborative tagging (a.k.a. folksonomy) systems have
      proliferated as a consequence of the growth of Web 2.0 communities. Constructing
      user profiles from folksonomy systems is useful for many applications such as
      personalized search and recommender systems. The identification of latent user
      communities is one way to better understand and meet user needs. The behavior of
      users is highly influenced by the behavior of their neighbors or community
      members, and this can be utilized in constructing user profiles. However,
      conventional user profiling techniques often encounter data sparsity problems as
      data from a single user is insufficient to build a powerful profile. Hence, in
      this paper we propose a method of enriching user profiles based on latent user
      communities in folksonomy data. Specifically, the proposed approach contains four
      sub-processes: (i) tag-based user profiles are extracted from a folksonomy
      tripartite graph; (ii) a multi-faceted folksonomy graph is constructed by
      integrating tag and image affinity subgraphs with the folksonomy tripartite
      graph; (iii) random walk distance is used to unify various relationships and
      measure user similarities; (iv) a novel prototype-based clustering method based
      on user similarities is used to identify user communities, which are further used
      to enrich the extracted user profiles. To evaluate the proposed method, we
      conducted experiments using a public dataset, the results of which show that our
      approach outperforms previous ones in user profile enrichment. 

PMID- 24907894
TI  - Challenges to research productivity of doctoral program nursing faculty.
AB  - The Institute of Medicine, responding to a national health care crisis and
      related nursing labor force concerns, has called for an increase in the
      proportion of registered nurses with baccalaureate or higher degrees to 80% and a
      doubling of the number of nurses with doctorates by 2020. Simultaneously, large
      numbers of senior faculty are starting to retire, whereas the movement of
      doctorally prepared nurses into academia is insufficient to replace them. Issues
      associated with the efforts of nursing programs to increase their capacity to
      respond to the Institute of Medicine's recommendations, particularly the effect
      on scholarly productivity among nursing faculty in doctoral programs, are
      examined in this article. Creative strategies for promoting scholarly
      productivity among doctoral program faculty are identified. 

PMID- 24907895
TI  - Nursing students' personal qualities: a descriptive study.
AB  - BACKGROUND: Reports of a lack of compassionate care from nurses have resulted in
      calls to integrate the assessment of personal qualities into nursing student
      selection, with the intent to recruit individuals whose attributes reflect those
      desired in the practising nurse. Whilst nursing programmes are able to determine
      students' academic abilities on enrolment limited attention has been given to
      other qualities. Although there is an understanding of the qualities desired in
      the practising nurse, to date there has been limited exploration of nursing
      students' personal qualities as they enter nursing programmes and whether these
      change over time. AIMS: To describe the personal qualities of newly enrolled
      Bachelor of Nursing students, and to determine if these qualities are age and
      gender specific and whether they change over time. METHODS: The Personal
      Qualities Assessment (PQA; www.pqa.net.au) was completed by 138 nursing students
      on enrolment and repeated after three years. RESULTS: Twenty four percent of
      students had PQA scores at the extreme ends (+/-2 SD) of the continuum of one or
      more sub-scale distributions. Significant positive correlations were found
      between age and the PQA measured traits: self-control, resilience, narcissism,
      empathy and moral orientation. Females were significantly more conscientious,
      community orientated and involved; males had significantly higher narcissism and
      aloofness scores and lower empathy. For those students (n=28) who completed the
      follow-up PQA, their personal qualities scores did not change. CONCLUSION: Most
      of the study sample possessed mid-range personal quality trait scores, but
      approximately a quarter of the nursing students recorded extreme scores. Older
      students were found to have a higher measure of self-control, resilience, empathy
      and narcissism and more communitarian in attitude. Significant differences were
      found between males' and females' scores. That personal qualities were unchanged
      after three years suggests the importance of incorporating the assessment of
      these qualities into selection and recruitment of nursing students.

PMID- 24907896
TI  - Prevalence rates for depression by industry: a claims database analysis.
AB  - PURPOSE: To estimate and interpret differences in depression prevalence rates
      among industries, using a large, group medical claims database. METHODS:
      Depression cases were identified by ICD-9 diagnosis code in a population of
      214,413 individuals employed during 2002-2005 by employers based in western
      Pennsylvania. Data were provided by Highmark, Inc. (Pittsburgh and Camp Hill,
      PA). Rates were adjusted for age, gender, and employee share of health care
      costs. National industry measures of psychological distress, work stress, and
      physical activity at work were also compiled from other data sources. RESULTS:
      Rates for clinical depression in 55 industries ranged from 6.9 to 16.2 %,
      (population rate = 10.45 %). Industries with the highest rates tended to be those
      which, on the national level, require frequent or difficult interactions with the
      public or clients, and have high levels of stress and low levels of physical
      activity. CONCLUSIONS: Additional research is needed to help identify industries
      with relatively high rates of depression in other regions and on the national
      level, and to determine whether these differences are due in part to specific
      work stress exposures and physical inactivity at work. CLINICAL SIGNIFICANCE:
      Claims database analyses may provide a cost-effective way to identify priorities
      for depression treatment and prevention in the workplace.

PMID- 24907897
TI  - Physical diseases among persons with obsessive compulsive symptoms and disorder:
      a general population study.
AB  - PURPOSE: This study aimed at evaluating the comorbidity between DSM-IV obsessive
      compulsive disorder (OCD) and subthreshold forms and physical diseases in the
      general population as well as disability associated with comorbidity. METHODS: We
      used data from the 1998 German Mental Health Survey, a representative survey of
      the German population. Mental disorders and physical diseases of 4181 subjects
      (aged 18-65) were cross-sectionally assessed. Mental disorders were diagnosed
      using the M-CIDI/DIA-X interview. Physical diseases were assessed through a self
      report questionnaire and a standardized medical interview. We created three
      groups of obsessive-compulsive symptoms: (1) no obsessive compulsive symptoms (n
      = 3,571); (2) obsessive compulsive symptoms (OCS, n = 371; endorsement of OCS
      (either obsession or compulsion) without fulfilling any core DSM-IV criteria);
      (3) subthreshold OCD/OCD (n = 239; fulfilling either some or all of the core DSM
      IV criteria). RESULTS: In comparison to subjects without OCS, subjects with
      subthreshold OCD/OCD showed higher prevalence rates of migraine headaches (OR
      1.7; 95% CI 1.1-2.5) and respiratory diseases (OR 1.7; 95% CI 1.03-2.7); subjects
      with OCS showed higher prevalence rates of allergies (OR 1.6; 95% CI 1.1-2.8),
      migraine headaches (OR 1.9; 95% CI 1.4-2.7) and thyroid disorders (OR 1.4; 95% CI
      1.01-2.0). Subjects with both OCS and physical disease reported the highest
      number of days of disability due to physical or psychological problems during the
      past 30 days compared to subjects with only OCS, only physical disease or neither
      of them. CONCLUSIONS: OCD and subthreshold forms are associated with higher
      comorbidity rates with specific physical diseases and higher disability than
      subjects without OCS. Possible etiological pathways should be evaluated in future
      studies and clinicians in primary care should be aware of these associations.

PMID- 24907898
TI  - Suicidal ideation and attempts among men who inject drugs in Delhi, India:
      psychological and social risk factors.
AB  - OBJECTIVE: Suicide is major public health problem in India. The objective of the
      analyses presented in this paper is to examine depressive and anxiety symptoms
      and socio-demographic indicators as correlates of suicidal ideation and attempts
      among people who inject drugs (PWID), a high-risk group for suicide. METHOD: We
      analysed data collected in April-May of 2012 from a community-based sample of 420
      PWID in Delhi using time location sampling. Self-report symptom scales were used
      to measure the severity of symptoms of depression (PHQ-9) and anxiety (GAD-2)
      within the preceding 2 weeks. We assessed the presence of suicidal thoughts
      within the past 12 months. RESULTS: Depressive and anxiety symptoms were
      associated with suicidal ideation, as were a range of social stressors including
      poor physical health, length of injecting drug use, housing insecurity, and
      experiences of violence and sexual abuse. However, depressive and anxiety
      symptoms were not associated with suicide attempts. Factors associated with
      suicide attempts among ideators were housing insecurity and relational dynamics
      including a poor relationship with family and, interestingly, being married.
      CONCLUSION: Suicide prevention interventions among this population should address
      not only individual mental health and addiction support needs but also the
      overwhelmingly poor psychosocial circumstances of this group.

PMID- 24907899
TI  - Institutionalization in incident dementia cases in comparison to age- and sex-
      matched controls: a 5-year follow-up from Germany.
AB  - BACKGROUND: Dementia is a main reason for nursing home admission. Information on
      institutionalization is often based on studies of limited methodological quality.
      We aimed to analyze time until nursing home admission since first coding of
      dementia diagnosis and factors associated with institutionalization in incident
      dementia patients compared to non-demented controls. METHODS: We analyzed claims
      data of a German Health insurance company including a cohort of 1,440 patients
      with a first diagnosis of dementia and 6,988 age- and sex-matched controls aged
      65 years and older. The follow-up was up to 5 years. We used Kaplan-Meier
      analysis for examining time until nursing home admission and cox regression for
      estimating crude and adjusted Hazard ratios. RESULTS: Dementia patients and
      controls were on average 78 years and about 55 % were males. The mean time to
      nursing home admission was 4.0 years in patients with dementia and 4.6 years for
      controls. After the 5-years observation-period 62.7 % (95 % CI 59.0-66.1) of
      dementia patients still lived in the community in comparison to 86.2 % (95 % CI
      85.2-87.2) of controls. Cox regression models show that the risk for
      institutionalization is 3.45 (95 % CI 3.05-3.90) times higher in dementia
      patients in comparison to controls when adjusted for sex, age, and comorbidity.
      CONCLUSIONS: Our analysis shows a significant influence of dementia on
      institutionalization in comparison to age- and sex-matched controls, especially
      in the youngest age groups. Hence, the results add substantial information on the
      disease progression of dementia and are, therefore, of great importance for
      health-care as well as long-term care planning.

PMID- 24907900
TI  - An orthogonal ribosome-tRNA pair via engineering of the peptidyl transferase
      center.
AB  - The Watson-Crick base pairs between the 3'-terminal end of tRNAs and ribosomal
      RNA in the peptidyl transferase center are universally conserved. Here, we report
      that the introduction of compensatory mutations to Escherichia coli RNAs in this
      site leads to an orthogonal system independent of the wild-type counterpart, as
      demonstrated via the production of two peptide sequences from a single mRNA. This
      work thus identifies a new way to reprogram the genetic code. 

PMID- 24907901
TI  - Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring.
AB  - For many drugs, finding the balance between efficacy and toxicity requires
      monitoring their concentrations in the patient's blood. Quantifying drug levels
      at the bedside or at home would have advantages in terms of therapeutic outcome
      and convenience, but current techniques require the setting of a diagnostic
      laboratory. We have developed semisynthetic bioluminescent sensors that permit
      precise measurements of drug concentrations in patient samples by spotting
      minimal volumes on paper and recording the signal using a simple point-and-shoot
      camera. Our sensors have a modular design consisting of a protein-based and a
      synthetic part and can be engineered to selectively recognize a wide range of
      drugs, including immunosuppressants, antiepileptics, anticancer agents and
      antiarrhythmics. This low-cost point-of-care method could make therapies safer,
      increase the convenience of doctors and patients and make therapeutic drug
      monitoring available in regions with poor infrastructure. 

PMID- 24907902
TI  - Humoral responses to herpesviruses are associated with neurodegeneration after a
      demyelinating event: results from the multi-center set study.
AB  - OBJECTIVES: To investigate the associations between antibody responses to
      herpesviruses and the development of thalamic, total deep gray matter, cortical
      and central atrophy in high-risk clinically isolated syndromes (CIS) after the
      first demyelinating event. METHODS: We analyzed volumetric brain outcomes in 193
      CIS patients enrolled in a multi-center study of high-risk CIS. All patients had
      2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal
      fluid. Serum samples obtained at the screening visit prior to any treatment were
      analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr
      virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon
      beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24
      months. RESULTS: Anti-EBV VCA highest quartile status was associated with
      regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity
      was associated with greater total deep gray matter atrophy and whole brain
      atrophy. Anti-EBV VCA highest quartile status was associated as trends with
      greater whole brain, gray matter atrophy and central atrophy. The associations of
      anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations
      with T2 lesions whereas the associations of anti-CMV positivity with deep gray
      matter atrophy were relatively independent of T2 lesions. CONCLUSIONS: Antibody
      responses to EBV and CMV are associated with global and regional brain atrophy in
      CIS patients treated with interferon-beta.

PMID- 24907903
TI  - Cerebrospinal fluid CXCL13 is a prognostic marker for aseptic meningitis.
AB  - In exceptional cases, patients with aseptic meningitis eventually develop aseptic
      meningoencephalitis. To find a candidate marker for the development of aseptic
      meningoencephalitis in adult patients diagnosed with aseptic meningitis, we
      compared 12 different cytokines/chemokines in cerebrospinal fluid (CSF) from 5
      patients with aseptic meningoencephalitis, 8 patients with aseptic meningitis,
      and 8 patients with control disease. Only the CXCL13 concentration was
      significantly elevated in the CSF of the group with aseptic meningoencephalitis
      compared with the group with aseptic meningitis. Thus, CSF CXCL13 may be a useful
      marker for predicting the prognosis of aseptic meningitis.

PMID- 24907904
TI  - An increased neutrophil-lymphocyte ratio in Alzheimer's disease is a function of
      age and is weakly correlated with neocortical amyloid accumulation.
AB  - Inflammation is a hallmark of Alzheimer's disease (AD). Whether directly involved
      in the pathogenesis, or a downstream consequence of neuronal death, the blood
      neutrophil-lymphocyte ratio (NLR) is reported to be a putative, non-invasive
      peripheral biomarker for AD. The aim of this study was to re-evaluate the
      diagnostic utility of longitudinal measures of the NLR. The NLR was stable across
      all time-points and weakly correlated with neocortical amyloid burden (R=0.21 at
      baseline, 0.27 at 18 months, 0.20 at 36 months and 0.10 at 54 months). Cross
      sectionally, the NLR was significantly elevated in AD participants as compared to
      HC participants at baseline (p<0.0001), 18 months (p<0.0001), 36 months (p=0.002)
      and at 54 months (p=0.007), however only prior to adjustment for age, sex and
      APOEepsilon4 allele status (p>0.05 at all time-points except for 18 months;
      p<0.0001). Longitudinally, the NLR was not significantly different between HC and
      AD participants (p>0.05) adjusted for age, sex and APOEepsilon4 allele status.
      Comparing the NLR between cognitive transition groups over time (transition
      towards an AD type dementia), there was no significant difference in the NLR
      levels between those participants, who did not transition and those participants
      who did transition, or those in the stable AD group after adjusting for age, sex
      and APOEepsilon4 allele status (p>0.05). Despite inflammation being a hallmark in
      AD and previous reports showing that the NLR can discriminate HC from AD
      patients, our results suggest that the sensitivity of the NLR itself is not
      robust enough for diagnostic utility. We identified significant relationships
      cross sectionally (p<0.05 at baseline, 18 months and 36 months) between the NLR
      and neocortical amyloid burden, but this relationship was lost after longitudinal
      analyses (p>0.5). The NLR also had limited association with cognitive decline,
      although in our cohort, the number of participants transitioning was relatively
      small. In conclusion, the NLR may reflect AD-related inflammatory processes in
      the periphery, but age and sex are dominant covariates which need to be
      controlled for in population-based screening.

PMID- 24907905
TI  - Localisation of citrullinated proteins in normal appearing white matter and
      lesions in the central nervous system in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease,
      considered to be autoimmune in origin. Post-translational modification of central
      nervous system proteins, including glial fibrillary acidic protein (GFAP) and
      myelin basic protein (MBP), through citrullination of arginine residues, may lead
      to exposure of neoepitopes, triggering autoimmunity. Here we investigated the
      expression of citrullinated proteins in active MS lesions, MS normal appearing
      white matter and control brain white matter. We demonstrate increased
      citrullinated GFAP and MBP by immunohistochemistry and western blotting in areas
      of ongoing demyelination, suggesting a pivotal role for deimination of GFAP and
      MBP in MS pathogenesis MS.

PMID- 24907906
TI  - Identification and characterization of a carboxysomal gamma-carbonic anhydrase
      from the cyanobacterium Nostoc sp. PCC 7120.
AB  - Carboxysomes are proteinaceous microcompartments that encapsulate carbonic
      anhydrase (CA) and ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco);
      carboxysomes, therefore, catalyze reversible HCO3 (-) dehydration and the
      subsequent fixation of CO2. The N- and C-terminal domains of the beta-carboxysome
      scaffold protein CcmM participate in a network of protein-protein interactions
      that are essential for carboxysome biogenesis, organization, and function. The N
      terminal domain of CcmM in the thermophile Thermosynechococcus elongatus BP-1 is
      also a catalytically active, redox regulated gamma-CA. To experimentally
      determine if CcmM from a mesophilic cyanobacterium is active, we cloned,
      expressed and purified recombinant, full-length CcmM from Nostoc sp. PCC 7120 as
      well as the N-terminal 209 amino acid gamma-CA-like domain. Both recombinant
      proteins displayed ethoxyzolamide-sensitive CA activity in mass spectrometric
      assays, as did the carboxysome-enriched TP fraction. NstCcmM209 was characterized
      as a moderately active and efficient gamma-CA with a k cat of 2.0 * 10(4) s(-1)
      and k cat/K m of 4.1 * 10(6) M(-1) s(-1) at 25  degrees C and pH 8, a pH optimum
      between 8 and 9.5 and a temperature optimum spanning 25-35  degrees C. NstCcmM209
      also catalyzed the hydrolysis of the CO2 analog carbonyl sulfide. Circular
      dichroism and intrinsic tryptophan fluorescence analysis demonstrated that
      NstCcmM209 was progressively and irreversibly denatured above 50  degrees C.
      NstCcmM209 activity was inhibited by the reducing agent
      tris(hydroxymethyl)phosphine, an effect that was fully reversed by a molar excess
      of diamide, a thiol oxidizing agent, consistent with oxidative activation being a
      universal regulatory mechanism of CcmM orthologs. Immunogold electron microscopy
      and Western blot analysis of TP pellets indicated that Rubisco and CcmM co
      localize and are concentrated in Nostoc sp. PCC 7120 carboxysomes. 

PMID- 24907907
TI  - Vaccination with DKK1-derived peptides promotes bone formation and bone mass in
      an aged mouse osteoporosis model.
AB  - The investigation of agents for the treatment of osteoporosis has been a long
      standing effort. The Wnt pathway plays an important role in bone formation and
      regeneration, and expression of Wnt pathway inhibitors, Dickkopf-1 (DKK1),
      appears to be associated with changes in bone mass. Inactivation of DKK1 leads to
      substantially increased bone mass in genetically manipulated animals. DKK1
      derived peptides (DDPs) were added to BMP2-stimulated MC3T3-E1 preosteoblastic
      cells in vitro to evaluate inhibitory activity of DDPs in MC3T3-E1 cell
      differentiation. Study was extended in vivo on old female mice to show whether or
      not inhibition of endogenous DKK1 biological activity using DDPs vaccination
      approach leads to increase of bone formation, bone density, and improvement of
      bone microstructure. We reported that synthetic DDPs were able to reduce alkaline
      phosphatase activity, prevent mineralization and inhibit the differentiation of
      MC3T3-E1 cells in vitro. Furthermore, vaccination with these DDPs in aged female
      mice 4 times for a total period of 22 weeks promoted bone mass and bone
      microstructure. 3D microCT and histomorphometric analysis showed that there were
      significant increase in bone mineral densities, improvement of bone
      microstructure and promotion of bone formation in the vaccinated mice, especially
      in the mice vaccinated with DDP-A and DDP-C. Histological and scanning electron
      microscopy image analysis also indicated that vaccination increased trabecular
      bone mass and significantly decreased fragmentation of bone fibers. Taken
      together, these preclinical results suggest that vaccination with DDPs represents
      a promising new therapeutic approach for the treatment of bone-related disorders,
      such as osteoporosis. 

PMID- 24907908
TI  - A positive role for anabolic androgenic steroids: preventing metabolic syndrome
      and type 2 diabetes mellitus.

PMID- 24907909
TI  - Reply of the authors.

PMID- 24907910
TI  - Sperm content of postacrosomal WW binding protein is related to fertilization
      outcomes in patients undergoing assisted reproductive technology.
AB  - OBJECTIVE: To determine the levels of postacrosomal WW binding protein (PAWP) in
      the spermatozoa of men that were used clinically for intracytoplasmic sperm
      injection (ICSI) and to correlate them with infertility treatment outcomes.
      DESIGN: Prospective clinical and laboratory study. SETTING: University-based
      laboratory and infertility clinic. PATIENT(S): Men undergoing ICSI for the
      treatment of couples' infertility (n=110). INTERVENTION(S): Quantitative analysis
      of sperm PAWP levels by flow cytometry and developmental analysis of PAWP
      expression by immunoblotting, immunofluorescence, and immunohistochemistry. MAIN
      OUTCOME MEASURE(S): PAWP flow-cytometric levels and immunolocalization in
      spermatozoa. RESULT(S): A strong positive correlation was found between PAWP
      expression levels and fertilization rates after ICSI, with high levels of PAWP
      being associated with higher fertilization rates; the positive correlation was
      independent of age, DNA fragmentation index, and other sperm parameters. PAWP
      expression levels were correlated with embryonic development, with high levels of
      PAWP being associated with a lower number of arrested embryos within 3-5 days
      post-ICSI. PAWP expression was detected during the late stages of human
      spermiogenesis in elongating spermatids, confirming previous findings in various
      animal models. CONCLUSION(S): Our clinical data from infertile couples
      demonstrate significant correlations between sperm PAWP levels and both
      fertilization rates and normal embryonic development after ICSI. Considering its
      proposed role in the initiation of oocyte activation, we suggest that PAWP could
      have potential applications in the diagnosis and treatment of infertility.

PMID- 24907911
TI  - Reply of the authors.

PMID- 24907912
TI  - Antimullerian hormone generation II assay nomogram.

PMID- 24907914
TI  - How many eggs should I freeze?

PMID- 24907913
TI  - Youth varicocele and varicocele treatment: a meta-analysis of semen outcomes.
AB  - OBJECTIVE: To study youth who have a varicocele or are undergoing varicocele
      treatment, in relation to changes in semen, as measured by semen analysis (SA).
      DESIGN: Meta-analysis of studies identified via a search of PubMed, Medline, and
      the Cochrane Library covering the last 40 years. SETTING: Not applicable.
      PATIENT(S): Youth from studies that assessed the presence and/or treatment of
      varicocele with SA. INTERVENTION(S): Selected studies were analyzed in two
      separate meta-analyses: one for the effect of varicocele on semen, as measured by
      SA (hypothesis #1), the other for the effect of treatment on semen, as measured
      by SA (hypothesis #2). MAIN OUTCOME MEASURE(S): A random-effects model was used
      to calculate weighted mean difference (WMD) of semen outcomes. Heterogeneity was
      calculated. Bias was assessed with funnel plots and Egger's test. RESULT(S): The
      initial literature search returned 1,180 potentially relevant articles. For
      hypothesis #1, 10 studies with a total of 357 varicocele and 427 control subjects
      were included. Sperm density, motility, and morphology were significantly
      decreased when associated with a varicocele, with a WMD of -24.0*10(6)/mL (95%
      confidence interval [CI; -39.5 to -8.6]), -7.5% (95% CI [-12.3% to -2.7%]), and 
      1.7% (95% CI [-2.4% to -1.1%]), respectively. Another 10 studies with 379 treated
      and 270 untreated subjects were analyzed for hypothesis #2. Sperm density and
      motility were significantly improved following treatment, with a WMD of
      14.6*10(6)/mL (95% CI [7.1-22.1]) and 6.6% (95% CI [2.1%-11.2%]), respectively.
      CONCLUSION(S): The presence of varicocele in youth appears to negatively affect
      sperm density, motility, and morphology. Treatment appears to result in moderate
      improvement of sperm density and mild improvement in sperm motility.

PMID- 24907915
TI  - Human chorionic gonadotropin vs. gonadotropin-releasing hormone agonist trigger
      in assisted reproductive technology--"the king is dead, long live the king!".

PMID- 24907916
TI  - Frequency of euploid miscarriage is increased in obese women with recurrent early
      pregnancy loss.
AB  - OBJECTIVE: To determine whether the frequency of euploid miscarriage is increased
      in obese women with recurrent early pregnancy loss (REPL). DESIGN: Observational
      cohort study using prospectively collected data. SETTING: Academic RPL program.
      PATIENT(S): A total of 372 women with REPL, defined as >=2 pregnancy losses<10
      weeks, and at least one ultrasound-documented miscarriage with chromosome
      results. INTERVENTION(S): Body mass index (BMI) was measured at the initial
      consultation and at each subsequent pregnancy. Conventional cytogenetic analysis
      and, when indicated, microsatellite analysis and/or comparative genomic
      hybridization was performed. MAIN OUTCOME MEASURE(S): Frequency of euploid
      miscarriage in obese (BMI>=30 kg/m2) and nonobese (BMI<30 kg/m2) subjects, before
      and subsequent to REPL evaluation. RESULT(S): There were 578 miscarriages with
      chromosome results. Of the subjects, 18% were obese at the time of miscarriage.
      The mean maternal age at miscarriage was similar between the obese and nonobese
      groups. Due to the high rate of maternal cell contamination in the prior
      miscarriages, only subsequent miscarriages with chromosome results were included
      in the primary analysis. Of the 117 subsequent miscarriages, the frequency of an
      euploid miscarriage among obese women was 58% compared with 37% of nonobese women
      (relative risk=1.63; 95% confidence interval 1.08-2.47). CONCLUSION(S): Obese
      women with REPL have an increased frequency of euploid miscarriage, which is a
      known risk factor for subsequent miscarriage.

PMID- 24907917
TI  - Cryopreservation and delayed embryo transfer-assisted reproductive technology
      registry and reporting implications.
AB  - Clinics performing assisted reproductive technology (ART) procedures have
      collected data via registry and publicly reported pregnancy outcomes for more
      than 25 years. During this time, the practice of ART has changed considerably
      with frozen embryo transfer (FET) procedures contributing an increasing
      proportion of live births. Cycles initiated with the intent of embryo banking for
      the purpose of fertility preservation have been excluded from these public
      reports, because pregnancy outcomes are not immediately available. An unintended
      consequence of the common sense handling of fertility preservation has been that
      cycles performed with intentional short-term cryopreservation of all embryos for
      other indications have also been excluded from the report. Over the last few
      years, cryopreservation with short-term delayed transfer increasingly has been
      performed for reasons other than fertility preservation. The pregnancy outcomes
      of these cycles are expected within a reasonable time frame and should be
      transparently reported. The Society for Assisted Reproductive Technology has
      collaborated with the Centers for Disease Control and Prevention to "recapture"
      these cycles for the public reports. This recapture is done by linking the FET
      cycles to the stimulation cycles from which the embryos were derived and by
      changing the labels of the outcome success metrics. Stimulations using ART,
      initiated for the purpose of transferring embryos within 1 year will be included
      in the report despite any prospective intent to freeze all eggs or embryos. A
      positive outcome will be reported when a live birth results from the first embryo
      transfer following stimulation ("primary transfer"). Linkage of ovarian
      stimulation and egg-retrieval procedures to FET will also allow development of
      other success metrics to further benefit fertility patients. 

PMID- 24907918
TI  - Smartphone-enabled health coach intervention for people with diabetes from a
      modest socioeconomic strata community: single-arm longitudinal feasibility study.
AB  - BACKGROUND: Lower socioeconomic strata (SES) populations have higher chronic
      disease risks. Smartphone-based interventions can support adoption of health
      behaviors that may, in turn, reduce the risks of type 2 diabetes-related
      complications, overcoming the obstacles that some patients may have with regular
      clinical contact (eg, shiftwork, travel difficulties, miscommunication).
      OBJECTIVE: The intent of the study was to develop and test a smartphone-assisted
      intervention that improves behavioral management of type 2 diabetes in an
      ethnically diverse, lower SES population within an urban community health
      setting. METHODS: This single-arm pilot study assessed a smartphone application
      developed with investigator assistance and delivered by health coaches.
      Participants were recruited from the Black Creek Community Health Centre in
      Toronto and had minimal prior experience with smartphones. RESULTS: A total of 21
      subjects consented and 19 participants completed the 6-month trial; 12 had
      baseline glycosylated hemoglobin (HbA1c) levels >7.0% and these subjects
      demonstrated a mean reduction of 0.43% (SD 0.63) (P<.05) with minimal changes in
      medication. CONCLUSIONS: This project supported the feasibility of smartphone
      based health coaching for individuals from lower SES with minimal prior
      smartphone experience.

PMID- 24907919
TI  - Supplementation of soybean lecithin-based semen extender by antioxidants:
      complementary flowcytometric study on post-thawed ram spermatozoa.
AB  - The purpose of the current study was to evaluate the effects of cysteine (C) and
      glutathione (G) on the post-thawed ram sperm quality. Collected semen samples
      from four mature rams were diluted with five soybean lecithin (SL)-based
      extenders containing: no antioxidant (SL-0), 5 mM cysteine (SL-C5), 10 mM
      cysteine (SL-C10), 5 mM glutathione (SL-G5) and 10 mM glutathione (SL-G10). After
      freeze-thawing process, motion and velocity parameters, plasma membrane integrity
      and functionality, morphological abnormality, lipid peroxidation, acrosomal
      status, mitochondria activity, and apoptosis status of post-thawed ram
      spermatozoa were assessed. The results showed that SL-C10 increased the total
      motility and plasma membrane integrity (p < 0.05) of post-thawed ram spermatozoa
      (55.86 +/- 1.37 and 60.57 +/- 1.34 %) compared to other extenders. Progressive
      motility was significantly higher in SL-C10 (24.71 +/- 1.13 %) compared to SL-0
      (20 +/- 1.13 %) and SL-G10 (15 +/- 1.13 %). Mitochondrial activity was
      significantly higher in SL-C10 (56.83 +/- 2.29 %) compared to SL-G10 (38.75 +/-
      2.29 %). Capacitation and acrosomal status, lipid peroxidation, and the
      percentage of dead spermatozoa were not affected by different extenders. The
      percentage of live spermatozoa was higher in SL-C10 (56.33 +/- 1.35 %) compared
      to other extenders. Also, SL-C10 resulted in a lower percentage of apoptotic
      spermatozoa (14.17 +/- 0.53 %) compared to other extenders. The results of this
      study showed that supplementation of SL-based ram semen extender with 10 mM
      cysteine resulted in an improved quality of post-thawed ram spermatozoa.

PMID- 24907920
TI  - Only acute dyspnea? High-grade osteosarcoma.

PMID- 24907921
TI  - Coexistence of silver and titanium dioxide nanoparticles: enhancing or reducing
      environmental risks?
AB  - Due to their bactericidal and photocatalytic characteristics, silver
      nanoparticles (Ag NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely
      used in the fields of environment and physiology. Once these untreated
      nanoparticles are released into an aquatic environment and encounter one another,
      there is more uncertainty about their fate and ecotoxicological risks compared
      with the single nanoparticles. To expand our knowledge of the health and
      environmental impacts of nanoparticles, we investigated the possible risk of the
      co-existence of TiO2 NPs and Ag NPs in an aquatic environment using ciliated
      protozoa (Tetrahymena pyriformis) as an aquatic animal model. In this study,
      silver ion (Ag(+)) release and physicochemical properties, as well as their
      effect on oxidative stress biomarkers, were monitored. Continuous illumination
      (12,000 lx) led to the 20.0% decrease in Ag(+) release in comparison with dark
      conditions, while TiO2 NPs and continuous illumination resulted in decreasing the
      Ag(+) concentration to 64.3% in contrast with Ag NPs-only suspensions. Toxicity
      tests indicated that different illumination modes exerted distinct effects of
      TiO2 NPs on the toxicity of Ag NPs: no effects, antagonism and synergism in dark,
      natural light and continuous light, respectively. In the presence of 1.5mg/L
      (18.8 MUM) TiO2 NPs, the toxicity of 1.5 mg/L (13.9 MUM) Ag NPs was reduced by
      28.7% and increased by 6.93% in natural light and 12,000 lx of continuous light,
      respectively. After culturing in 12,000 lx continuous light for 24h, SOD activity
      of the light control surged to 1.96 times compared to the dark control (P<0.001).
      TiO2 NPs induced a reduction of CAT activity by an average of (36.1+/-1.7) % in
      the light. In the natural light reductions in the toxicity of Ag, NPs decrease
      Ag(+) concentrations via adsorption of Ag(+) onto TiO2 NPs surfaces. The
      enhancement of Ag NPs toxicity can contribute to the formation of activated TiO2
      Ag NPs complexes in continuous light. The existence of TiO2 NPs in various
      illumination modes changed the surface chemistry of Ag NPs and then led to
      different toxicity effects. TiO2 NPs reduce the environmental risks of Ag NPs in
      natural light, but in continuous light, TiO2 NPs enhance the environmental risks
      of Ag NPs.

PMID- 24907922
TI  - Influence of PbS nanoparticle polymer coating on their aggregation behavior and
      toxicity to the green algae Dunaliella salina.
AB  - The potential hazards of nanoparticles (NPs) to the environment and to living
      organisms need to be considered for a safe development of nanotechnology. In the
      present study, the potential toxic effects of uncoated and gum Arabic-coated lead
      sulfide nanoparticles (GA-coated PbS NPs) on the growth, lipid peroxidation,
      reducing capacity and total carotenoid content of the hypersaline unicellular
      green algae Dunaliella salina were investigated. Coatings of PbS NPs with GA, as
      confirmed by Fourier transform infrared spectroscopy, reduced the toxicity of PbS
      NPs. Uncoated PbS NP toxicity to D. salina was attributed to higher algal cell-NP
      agglomerate formation, higher lipid peroxidation, lower content of total reducing
      substances and lower total carotenoid content. Low levels of Pb(2+) in the growth
      culture media indicate that PbS NP dissolution does not occur in the culture.
      Also, the addition of 100 MUM Pb(2+) to the culture media had no significant
      (P>0.05) effect on algal growth. The shading of light (shading effect) by PbS
      NPs, when simulated using activated charcoal, did not contribute to the overall
      toxic effect of PbS NPs which was evident by insignificant (P>0.05) reduction in
      the growth and antioxidant capacity of the algae. When PbS NP aggregation in
      culture media (without algal cells) was followed for 60 min, uncoated form
      aggregated rapidly reaching aggregate sizes with hydrodynamic diameter of over
      2500 nm within 60 min. Effective particle-particle interaction was reduced in the
      GA-coated NPs. Aggregates of about 440 nm hydrodynamic diameter were formed
      within 35 min. Afterwards the aggregate size remained constant. It is concluded
      that PbS NPs have a negative effect on aquatic algae and their transformation by
      GA capping affects NPs aggregation properties and toxicity.

PMID- 24907923
TI  - A primary FIsh Gill Cell System (FIGCS) for environmental monitoring of river
      waters.
AB  - Studies were conducted to assess the feasibility of a primary FIsh Gill Cell
      culture system (FIGCS) for both laboratory and field based environmental
      monitoring of rivers known to be affected by metal contamination. FIGCS were
      exposed in the laboratory and in the field to water from the River Hayle, a metal
      contaminated system in Cornwall, United Kingdom. Water chemistry, including
      transition metal concentrations, changes in transepithelial electrical resistance
      (TEER), cell viability and the expression of metal responsive genes,
      metallothionein A and B were measured. FIGCS tolerated river water in the
      laboratory showing no loss in TEER or cell viability following 24h exposure. The
      cells also tolerated transport to the field (~1000 km and 30 h) and exposure to
      unfiltered and filtered river water. Metallothionein A and B, a measure of
      intracellular biologically active metals, expression was induced in the
      laboratory and field on exposure to water from sites with elevated metal
      concentrations compared to those sites where metal levels were below water metal
      Environmental Quality Standards. This demonstrates that FIGCS detects bioreactive
      metals in river waters on exposure in the laboratory or field and can be used for
      on-site environmental monitoring as well as investigations into bioavailability
      and toxicity of contaminant mixtures in natural waters.

PMID- 24907924
TI  - Progressive lung calcification after orthotopic heart transplant.
AB  - Focal, asymmetrical pulmonary airspace opacities in post-transplant setting are
      commonly from infection, hemorrhage, edema or infarction. Rarely, stable or
      mildly progressive dense pulmonary opacities are due to pulmonary calcifications.
      In the majority of cases, these are asymptomatic and warrant no further
      intervention. 

PMID- 24907925
TI  - Brain ketones detected by proton magnetic resonance spectroscopy in an infant
      with Ohtahara syndrome treated with ketogenic diet.
AB  - Atypical resonances on proton magnetic resonance spectroscopy (MRS) examinations
      are occasionally found in children undergoing a metabolic evaluation for
      neurological conditions. While a radiologist's first instinct is to suspect a
      pathological metabolite, usually the origin of the resonance arises from an
      exogenous source. We report the appearance of distinct resonances associated with
      a ketogenic diet in a male infant presenting with Ohtahara syndrome. These
      resonances can be confused in interpretation with lactate and glutamate. To
      confirm assignments, the basis set for quantification was supplemented with
      simulations of beta-hydroxybutyrate, acetone and acetoacetate in LCModel
      spectroscopy processing software. We were able to quantitate the levels of end
      products of a ketogenic diet and illustrate how to distinguish these resonances. 

PMID- 24907926
TI  - In situ micropillar compression reveals superior strength and ductility but an
      absence of damage in lamellar bone.
AB  - Ageing societies suffer from an increasing incidence of bone fractures. Bone
      strength depends on the amount of mineral measured by clinical densitometry, but
      also on the micromechanical properties of the hierarchical organization of bone.
      Here, we investigate the mechanical response under monotonic and cyclic
      compression of both single osteonal lamellae and macroscopic samples containing
      numerous osteons. Micropillar compression tests in a scanning electron
      microscope, microindentation and macroscopic compression tests were performed on
      dry ovine bone to identify the elastic modulus, yield stress, plastic
      deformation, damage accumulation and failure mechanisms. We found that isolated
      lamellae exhibit a plastic behaviour, with higher yield stress and ductility but
      no damage. In agreement with a proposed rheological model, these experiments
      illustrate a transition from a ductile mechanical behaviour of bone at the
      microscale to a quasi-brittle response driven by the growth of cracks along
      interfaces or in the vicinity of pores at the macroscale. 

PMID- 24907928
TI  - Electrostatic control of block copolymer morphology.
AB  - Energy storage is at present one of the foremost issues society faces. However,
      material challenges now serve as bottlenecks in technological progress. Lithium
      ion batteries are the current gold standard to meet energy storage needs;
      however, they are limited owing to the inherent instability of liquid
      electrolytes. Block copolymers can self-assemble into nanostructures that
      simultaneously facilitate ion transport and provide mechanical stability. The
      ions themselves have a profound, yet previously unpredictable, effect on how
      these nanostructures assemble and thus the efficiency of ion transport. Here we
      demonstrate that varying the charge of a block copolymer is a powerful mechanism
      to predictably tune nanostructures. In particular, we demonstrate that highly
      asymmetric charge cohesion effects can induce the formation of nanostructures
      that are inaccessible to conventional uncharged block copolymers, including
      percolated phases desired for ion transport. This vastly expands the design space
      for block copolymer materials and is informative for the versatile design of
      battery electrolyte materials. 

PMID- 24907927
TI  - Etchable plasmonic nanoparticle probes to image and quantify cellular
      internalization.
AB  - There is considerable interest in using nanoparticles as labels or to deliver
      drugs and other bioactive compounds to cells in vitro and in vivo. Fluorescent
      imaging, commonly used to study internalization and subcellular localization of
      nanoparticles, does not allow unequivocal distinction between cell surface-bound
      and internalized particles, as there is no methodology to turn particles 'off'.
      We have developed a simple technique to rapidly remove silver nanoparticles
      outside living cells, leaving only the internalized pool for imaging or
      quantification. The silver nanoparticle (AgNP) etching is based on the
      sensitivity of Ag to a hexacyanoferrate-thiosulphate redox-based destain
      solution. In demonstration of the technique we present a class of multicoloured
      plasmonic nanoprobes comprising dye-labelled AgNPs that are exceptionally bright
      and photostable, carry peptides as model targeting ligands, can be etched rapidly
      and with minimal toxicity in mice, and that show tumour uptake in vivo. 

PMID- 24907930
TI  - Discerning the kinetics of autoimmune manifestations in a model of Sjogren's
      syndrome.
AB  - Ectopic follicles are non-encapsulated organized lymphoid structures that form at
      sites of inflammation and presumably contribute to the activation and
      differentiation of cells with autoreactive potential within target tissues. As
      such, directed targeting of ectopic follicles in settings of autoimmunity may
      provide a means to specifically inhibit the activation of autoreactive cells
      without impairing protective immune responses ongoing in peripheral lymphoid
      tissues. NOD.H2h4 mice are a non-diabetic strain of NOD mice which develop a
      Sjogren's syndrome-like disease which includes the formation of ectopic follicles
      in the salivary gland and characteristic Sjogren's autoantibodies. The goal of
      these studies was to better characterize the formation of ectopic follicles in
      this model and to explore their contribution to autoimmunity. Our studies show
      that by 8 weeks of age, young NOD.H2h4 mice spontaneously develop an abundance of
      splenic germinal centers, prior to the emergence of lymphocyte infiltration in
      the salivary gland tissue. Ectopic follicle formation in the salivary gland
      begins to appear in these mice between 12 and 16 weeks of age. Interestingly,
      anti-Ro and anti-La autoantibodies precede the development of ectopic follicles
      in young NOD.H2h4 mice. In contrast, production of anti-dsDNA antibodies is
      delayed and largely coincides with the formation of ectopic follicles in these
      mice. These data suggest that tertiary lymphoid structures may arise from the
      trafficking of activated T and B cells to sites of inflammation in non-lymphoid
      tissues. Furthermore, local presentation of autoantigens may then promote the
      expansion of autoreactive cells with specificities distinct from those generated
      in the splenic micro-environment. 

PMID- 24907929
TI  - Air-stable n-type colloidal quantum dot solids.
AB  - Colloidal quantum dots (CQDs) offer promise in flexible electronics, light
      sensing and energy conversion. These applications rely on rectifying junctions
      that require the creation of high-quality CQD solids that are controllably n-type
      (electron-rich) or p-type (hole-rich). Unfortunately, n-type semiconductors made
      using soft matter are notoriously prone to oxidation within minutes of air
      exposure. Here we report high-performance, air-stable n-type CQD solids. Using
      density functional theory we identify inorganic passivants that bind strongly to
      the CQD surface and repel oxidative attack. A materials processing strategy that
      wards off strong protic attack by polar solvents enabled the synthesis of an air
      stable n-type PbS CQD solid. This material was used to build an air-processed
      inverted quantum junction device, which shows the highest current density from
      any CQD solar cell and a solar power conversion efficiency as high as 8%. We also
      feature the n-type CQD solid in the rapid, sensitive, and specific detection of
      atmospheric NO2. This work paves the way for new families of electronic devices
      that leverage air-stable quantum-tuned materials. 

PMID- 24907931
TI  - D-galactose induced inflammation lipid peroxidation and platelet activation in
      rats.
AB  - BACKGROUND: To investigate events possibly related to the development of D
      galactose induced senescence, we examined whether 8-iso PGF(2alpha) formation, a
      marker of in vivo lipid peroxidation is altered and whether its biosynthesis is
      associated with 11-dehydro-TXB(2) excretion rate, as a marker of in vivo platelet
      activation. In this setting, we also investigated the relationship between
      proinflammatory mediators (IL-6 and TNF-alpha from one, and lipid peroxidation
      and platelet activation, from another aspect. METHODS AND RESULTS: Forty animals
      were divided, depending on treatment with d-galactose into: placebo and D
      galactose treated rats. 8-iso-PGF(2alpha), IL-6 and TNF-alpha were measured in
      plasma, while 11-dehydro-TXB(2) was determined in the urine after a six week
      treatment with d-galactose. Compared to placebo, d-galactose treated animals
      showed significantly higher levels of all measured parameters. CONCLUSIONS: D
      galactose induced changes in the rate of F(2)-isoprostane formation are
      associated with the changes in the excretion rate of 11-dehydro-TXB(2).

PMID- 24907932
TI  - Quantum chemical characterization of zwitterionic structures: Supramolecular
      complexes for modifying the wettability of oil-water-limestone system.
AB  - In this work, we present a quantum chemical study pertaining to some
      supramolecular complexes acting as wettability modifiers of oil-water-limestone
      system. The complexes studied are derived from zwitterionic liquids of the types
      N'-alkyl-bis, N-alquenil, N-cycloalkyl, N-amyl-bis-beta amino acid or salts
      acting as sparkling agents. We studied two molecules of zwitterionic liquids
      (ZL10 and ZL13), HOMO and LUMO levels, and the energy gap between them, were
      calculated, as well as the electron affinity (EA) and ionization potential (IP),
      chemical potential, chemical hardness, chemical electrophilicity index and
      selectivity descriptors such Fukui indices. In this work, electrochemical
      comparison was realized with cocamidopropyl betaine (CPB), which is a structure
      zwitterionic liquid type, nowadays widely applied in enhanced recovery processes.

PMID- 24907933
TI  - Theoretical study of gamma-hexachlorocyclohexane and beta-hexachlorocyclohexane
      isomers interaction with surface groups of activated carbon model.
AB  - Activated carbon (AC) is employed in drinking water purification without almost
      any knowledge about the adsorption mechanism of persistent organic pollutants
      (POPs) onto it. Hexachlorocyclohexane (HCH) is an organochlorinated contaminant
      present in water and soils of banana crops production zones of the Caribbean. The
      most relevant isomers of HCH are gamma-HCH and beta-HCH, both with great
      environmental persistence. A theoretical study of the influence of AC surface
      groups (SGs) on HCH adsorption is done in order to help to understand the process
      and may lead to improve the AC selection process. A simplified AC model
      consisting of naphthalene with a functional group was used to assess the
      influence of SGs over the adsorption process. The Multiple Minima Hypersurface
      (MMH) methodology was employed to study gamma-HCH and beta-HCH interactions with
      different AC SGs (hydroxyl and carboxyl) under different hydration and pH
      conditions. The results obtained showed that association of HCH with SGs
      preferentially occurs between the axial protons of HCH and SG's oxygen atom, and
      the most favorable interactions occurring with charged SGs. An increase in
      carboxylic SGs content is proposed to enhance HCH adsorption onto AC under
      neutral pH conditions. Finally, this work presents an inexpensive computer aided
      methodology for preselecting activated carbon SGs content for the removal of a
      given compound. 

PMID- 24907934
TI  - Changes of proteins induced by anticoagulants can be more sensitively detected in
      urine than in plasma.
AB  - The most fundamental property of biomarkers is change. But changes are hard to
      maintain in plasma since it is strictly controlled by homeostatic mechanisms of
      the body. There is no homeostatic mechanism for urine. Besides, urine is partly a
      filtration of blood, and systematic information can be reflected in urine. We
      hypothesize that change of blood can be reflected in urine more sensitively. Here
      we introduce the interference into the blood by two anticoagulants heparin or
      argatroban. Plasma and urine proteins were profiled by LC-MS/MS and then
      validated by Western blot in totally six SD female rats before and after the drug
      treatments. In argatroban treated group, with exactly the same experimental
      procedure and the same cutoff value for both plasma and urine proteins, 62
      proteins changed in urine, only one of which changed in plasma. In heparin
      treated group, 27 proteins changed in urine but only three other proteins changed
      in plasma. Both LC-MS/MS and Western blot analyses demonstrated drug-induced
      increases in transferrin and hemopexin levels in urine but not in plasma. Our
      data indicates that urine may serve as a source for more sensitive detection of
      protein biomarkers than plasma. 

PMID- 24907936
TI  - The new emerging H7N9 influenza virus indicates poultry as new mixing vessels.

PMID- 24907935
TI  - Kindlin-2 expression in adult tissues correlates with their embryonic origins.
AB  - Kindlin-2 functions in the maintenance of homeostasis and in human diseases. This
      study investigated the interrelationship between Kindlin-2 expression in tissues
      and the corresponding germ layers from which these tissues originated. Kindlin-2
      expression was examined in normal adult human organs and human cancer tissues by
      immunohistochemical analyses. Analysis of Kindlin-2 mRNA levels in adult human
      organs in the Oncomine dataset revealed Kindlin-2 is highly expressed in mesoderm
      derived organs. However, Kindlin-2 was negative or weakly expressed in
      endoderm/ectoderm-derived organs. Interestingly, the abnormal expression of
      Kindlin-2 was observed in a variety of human cancers. In agreement with its
      expression profile in humans, Kindlin-2 was also highly expressed in mesoderm
      derived organs in mouse embryos with the exception of strong Kindlin-2 expression
      in ectoderm-derived spinal cord and ganglia, tissues that are highly mobile
      during embryonic development. Importantly, we demonstrated the expression level
      of Kindlin-2 in adult organs correlated with their embryonic dermal origins and
      deregulation of Kindlin-2 in tissues is associated with tumor progression. This
      finding will help us understand the dual role of Kindlin-2 in the regulation of
      tumor progression and embryonic development. 

PMID- 24907937
TI  - RNA-Seq analysis of yak ovary: improving yak gene structure information and
      mining reproduction-related genes.
AB  - RNA-Seq, a high-throughput (HT) sequencing technique, has been used effectively
      in large-scale transcriptomic studies, and is particularly useful for improving
      gene structure information and mining of new genes. In this study, RNA-Seq HT
      technology was employed to analyze the transcriptome of yak ovary. After Illumina
      Solexa deep sequencing, 26826516 clean reads with a total of 4828772880 bp were
      obtained from the ovary library. Alignment analysis showed that 16992 yak genes
      mapped to the yak genome and 3734 of these genes were involved in alternative
      splicing. Gene structure refinement analysis showed that 7340 genes that were
      annotated in the yak genome could be extended at the 5' or 3' ends based on the
      alignments been the transcripts and the genome sequence. Novel transcript
      prediction analysis identified 6321 new transcripts with lengths ranging from 180
      to 14884 bp, and 2267 of them were predicted to code proteins. BLAST analysis of
      the new transcripts showed that 1200?4933 mapped to the non-redundant (nr),
      nucleotide (nt) and/or SwissProt sequence databases. Comparative statistical
      analysis of the new mapped transcripts showed that the majority of them were
      similar to genes in Bos taurus (41.4%), Bos grunniens mutus (33.0%), Ovis aries
      (6.3%), Homo sapiens (2.8%), Mus musculus (1.6%) and other species. Functional
      analysis showed that these expressed genes were involved in various Gene Ontology
      (GO) categories and Kyoto Encyclopedia of Genes and Genomes pathways. GO analysis
      of the new transcripts found that the largest proportion of them was associated
      with reproduction. The results of this study will provide a basis for describing
      the normal transcriptome map of yak ovary and for future studies on yak breeding
      performance. Moreover, the results confirmed that RNA-Seq HT technology is highly
      advantageous in improving gene structure information and mining of new genes, as
      well as in providing valuable data to expand the yak genome information.

PMID- 24907938
TI  - Cascade effects of crop species richness on the diversity of pest insects and
      their natural enemies.
AB  - Understanding how plant species richness influences the diversity of herbivorous
      and predatory/parasitic arthropods is central to community ecology. We explore
      the effects of crop species richness on the diversity of pest insects and their
      natural enemies. Using data from a four-year experiment with five levels of crop
      species richness, we found that crop species richness significantly affected the
      pest species richness, but there were no significant effects on richness of the
      pests' natural enemies. In contrast, the species richness of pest insects
      significantly affected their natural enemies. These findings suggest a cascade
      effect where trophic interactions are strong between adjacent trophic levels,
      while the interactions between connected but nonadjacent trophic levels are
      weakened by the intermediate trophic level. High crop species richness resulted
      in a more stable arthropod community compared with communities in monoculture
      crops. Our results highlight the complicated cross-trophic interactions and the
      crucial role of crop diversity in the food webs of agro-ecosystems. 

PMID- 24907939
TI  - Advances in preimplantation genetic diagnosis/screening.
AB  - Preimplantation genetic diagnosis (PGD) gives couples who have a high risk of
      transmitting genetic disorders to their baby the chance to have a healthy
      offspring through embryo genetic analysis and selection. Preimplantation genetic
      screening (PGS) is an effective method to select euploid embryos that may prevent
      repeated implantation failure or miscarriage. However, how and to whom PGS should
      be provided is a controversial topic. The first successful case of PGD of a human
      being was reported in 1990, and there have been tremendous improvements in this
      technology since then. Both embryo biopsy and genetic technologies have been
      improved dramatically, which increase the accuracy and expand the indications of
      PGD/PGS. 

PMID- 24907940
TI  - Whole-body [18F]FDG PET/MRI vs. PET/CT in the assessment of bone lesions in
      oncological patients: initial results.
AB  - OBJECTIVES: To compare [(18)F]FDG PET/MRI with PET/CT for the assessment of bone
      lesions in oncologic patients. METHODS: This prospective study included 67
      patients with solid tumours scheduled for PET/CT with [(18)F]FDG who also
      underwent a whole-body PET/MRI scan. The datasets (PET/CT, PET/MRI) were rated by
      two readers regarding lesion conspicuity (four-point scale) and diagnostic
      confidence (five-point scale). Median scores were compared using the Wilcoxon
      test. RESULTS: Bone metastases were present in ten patients (15%), and benign
      bone lesions in 15 patients (22%). Bone metastases were predominantly localized
      in the pelvis (18 lesions, 38%) and the spine (14 lesions, 29%). Benign bone
      lesions were exclusively osteosclerotic and smaller than the metastases (mean
      size 6 mm vs. 23 mm). While PET/CT allowed identification of 45 of 48 bone
      metastases (94%), PET/MRI allowed identification of all bone metastases (100%).
      Conspicuity of metastases was high for both modalities with significantly better
      results using PET/MRI (p < 0.05). Diagnostic confidence in lesion detection was
      high for both modalities without a significant difference. In benign lesions,
      conspicuity and diagnostic confidence were significantly higher with PET/CT (p <
      0.05). CONCLUSIONS: [(18)F]FDG PET/MRI shows high potential for the assessment of
      bone metastases by offering superior lesion conspicuity when compared to PET/CT.
      In hypersclerotic, benign bone lesions PET/CT still sets the reference. KEY
      POINTS: * PET/MRI and PET/CT are of equal value for the identification of disease
      positive patients * PET/MRI offers higher lesion conspicuity as well as
      diagnostic confidence * PET/MRI is an attractive new alternative for the
      assessment of bone metastases.

PMID- 24907941
TI  - PACAP38 suppresses cortical damage in mice with traumatic brain injury by
      enhancing antioxidant activity.
AB  - The production of reactive oxygen species (ROS) and the resulting oxidative
      stress in mice in response to a controlled cortical impact (CCI) are typical
      exacerbating factors associated with traumatic brain injury (TBI). Pituitary
      adenylate cyclase-activating polypeptide 38 (PACAP38) is a multifunctional
      peptide that has been shown to exhibit neuroprotective effects in response to a
      diverse range of injuries to neuronal cells. We recently reported that PACAP38
      might regulate oxidative stress in mice. The aim of the present study was to
      determine whether PACAP38 exerts neuroprotective effects by regulating oxidative
      stress in mice with TBI. Reactive oxidative metabolites (ROMs) and biological
      antioxidant potential (BAP) were measured in male C57Bl/6 mice before and 3, 4,
      and 24 h after CCI. PACAP38 was administered intravenously immediately following
      CCI, and immunostaining for the oxidative stress indicator nitrotyrosine (NT),
      and for neuronal death as an indicator of the area affected by TBI, was measured
      24 h later. Western blot experiments to determine antioxidant activity [as
      indicated by superoxide dismutase-2 (SOD-2) and glutathione peroxidase 1 (GPx-1)]
      in the neocortical region were also performed 3 h post-CCI. Results showed that
      plasma BAP and ROM levels were dramatically increased 3 h after CCI. PACAP38
      suppressed the extent of TBI and NT-positive regions 24 h after CCI, and
      increased SOD-2 and GPx-1 levels in both hemispheres. Taken together, these
      results suggest that increasing antioxidant might be involving in the
      neuroprotective effect of PACAP38 in mice subjected to a CCI.

PMID- 24907943
TI  - Immunohistochemistry and other ancillary techniques in the diagnosis of
      gestational trophoblastic diseases.
AB  - Gestational trophoblastic disease (GTD) encompasses entities ranging from
      ubiquitous hydatidiform moles to rare neoplastic gestational trophoblastic
      tumors. In practice, the histological diagnosis of GTD continues to have
      significant diagnostic inaccuracy with marked inter- and intra-observer
      variability, even among expert pathologists. Studies in correlation with
      genotypic evidence have confirmed a lack of accuracy in diagnosis of hydatidiform
      moles using histology alone. Applications of new immunohistochemical markers and
      molecular techniques have significantly enhanced the diagnostic precision of
      various GTDs in recent years. p57 Immunohistochemistry is a highly useful marker
      in confirming complete hydatidiform mole. PCR-based DNA genotyping has emerged as
      a powerful diagnostic measure to precisely classify both complete and partial
      hydatidiform moles. With acquisition of molecular diagnostic capabilities at most
      medical centers, these ancillary techniques have been increasingly integrated
      into the routine diagnostic workup of GTD. We propose an algorithmic approach
      combining histology and these ancillary tests to provide the best diagnostic
      practice possible. Under this algorithm, all cases with histological suspicion
      for complete mole are subject to p57 immunohistochemical confirmation, and all
      cases with histological suspicion for partial mole undergo DNA genotyping workup.
      Beyond hydatidiform mole, recognition of gestational trophoblastic tumors
      requires a high index of suspicion and application of immunohistochemical markers
      of trophoblast is helpful to accurately diagnose these rare tumors. 

PMID- 24907942
TI  - The anti-aging and tumor suppressor protein Klotho enhances differentiation of a
      human oligodendrocytic hybrid cell line.
AB  - Klotho functions as an aging suppressor, which, in mice, extends lifespan when
      overexpressed and accelerates development of aging-like phenotypes when
      disrupted. Klotho is mainly expressed in brain and kidney and is secreted into
      the serum and CSF. We have previously shown that Klotho is reduced in brains of
      old monkeys, rats, and mice. We further reported the ability of Klotho to enhance
      oligodendrocyte differentiation and myelination. Here, we examined the signaling
      pathways induced by Klotho in MO3.13, a human oligodendrocytic hybrid cell line.
      We show that exogenous Klotho affects the ERK and Akt signaling pathways,
      decreases the proliferative abilities and enhances differentiation of MO3.13
      cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a
      massive change in gene expression with 80 % of the differentially expressed genes
      being downregulated. Using gene set enrichment analysis, we predicted potential
      transcription factors involved in regulating Klotho-treated MO3.13 cells and
      found that these cells are highly enriched in the gene sets, that are similarly
      observed in cancer, cardiovascular disease, stress, aging, and hormone-related
      chemical and genetic perturbations. Since Klotho is downregulated in all brain
      tumors tested to date, enhancing Klotho has therapeutic potential for treating
      brain and other malignancies.

PMID- 24907944
TI  - Improving coenzyme Q8 production in Escherichia coli employing multiple
      strategies.
AB  - Coenzyme Q (CoQ) is a medically valuable compound and a high yielding strain for
      CoQ will have several benefits for the industrial production of CoQ. To increase
      the CoQ(8) content of E. coli, we blocked the pathway for the synthesis of
      menaquinone by deleting the menA gene. The blocking of menaquinone pathway
      increased the CoQ(8) content by 81 % in E. coli (DeltamenA). To study the CoQ
      producing potential of E. coli, we employed previous known increasing strategies
      for systematic metabolic engineering. These include the supplementation with
      substrate precursors and the co-expression of rate-limiting genes. The co
      expression of dxs-ubiA and the supplementation with substrate precursors such as
      pyruvate (PYR) and parahydroxybenzoic acid (pHBA) increased the content of CoQ(8)
      in E. coli (DeltamenA) by 125 and 59 %, respectively. Moreover, a 180 % increase
      in the CoQ(8) content in E. coli (DeltamenA) was realized by the combination of
      the co-expression of dxs-ubiA and the supplementation with PYR and pHBA. All in
      all, CoQ(8) content in E. coli increased 4.06 times by blocking the menaquinone
      pathway, dxs-ubiA co-expression and the addition of sodium pyruvate and
      parahydroxybenzoic acid to the medium. Results suggested a synergistic effect
      among different metabolic engineering strategies.

PMID- 24907945
TI  - Pattern of abortion care in a tertiary level maternity hospital in Nepal.
AB  - INTRODUCTION: Complications from unsafe abortion are believed to account for the
      largest proportion of hospital admissions for gynaecological services in
      developing countries and not to mention the cost it imparts to the health system
      of a country. Therefore, it is equally important to find out the prevalence and
      the pattern of abortion among the women who utilize the safe abortion care
      services and provide a framework to target various health promotion programs
      including safe-motherhood and reproductive health; such that the future
      interventions to avoid the unintended pregnancy and unsafe abortion can be
      implemented accordingly. METHODS: A cross-sectional study was conducted in a
      tertiary care hospital in Kathmandu, Nepal. Social and demographic information of
      all the women seeking induced abortions from January 2011 to December 2012 were
      included and the result was analyzed. RESULT: Abortion contributed to about 1.68%
      of the total patient served in the hospital that provides both obstetrical and
      gynecological services. Of the total 4830 patients who underwent induced abortion
      in this period, the mean age was 27, 92.3% were from the Kathmandu valley and
      more than one-third women (35.2%) were illiterate who couldn't read and write.
      Majorities were more than two parity and belonged to higher caste. CONCLUSION:
      The socio-demographic profile of the abortion clients in Nepal has remained
      similar over the years. We need to address the accessibility and availability to
      the safe abortion care services along with other safe motherhood programs
      guaranteeing access to safe abortion and post-abortion care to all group of women
      and also, women education regarding contraception to avoid repeated abortions or
      unwanted pregnancy in the future.

PMID- 24907946
TI  - Prophylactic nasogastric decompression after emergency laparotomy.
AB  - INTRODUCTION: Post-operative nasogastric intubation after emergency laparotomy is
      a common practice in many centers, with the intent of hastening the return of
      bowel function, relieving gastrointestinal discomfort, reducing various post
      operative complications and reducing hospital stay. However, bowel rest and
      gastric decompression have been re-examined in the light of more recent data.
      Many studies and meta-analyses over the last 50 years have challenged the routine
      use of nasogastric tubes after laparotomy. The objective of this study is to
      evaluate the need for routine nasogastric decompression after emergency
      laparotomy. METHODS: A prospective, randomized controlled trial was conducted for
      12 months (May 1, 2007 to Apr 30, 2008) in the Department of Surgery, Tribhuvan
      University Teaching Hospital, after ethical approval. Patients were enrolled as
      per criteria (Box 1), and subsequently allocated by simple randomization into two
      groups: Group 1 and Group 2. Patients undergoing emergency laparotomy for
      perforation peritonitis, intestinal obstruction and abdominal trauma were
      randomized to two groups - with or without nasogastric tube after surgery.
      Gastric upset, return of bowel function and postoperative complications were
      compared. RESULTS: Total of 115 patients met the inclusion criteria. There was no
      statistically significant difference in the occurrence of gastric upset (P:
      0.38), wound complications (P: 0.30), respiratory complications (P: 0.30) and
      anastomotic leak (P: 0.64) between two groups. Bowel function returned in
      comparable times in both groups (correlation coefficient: 0.14; P: 0.54).
      Nasogastric tube had to be reinserted in three patients in the group with
      nasogastric decompression postoperatively, and four in the group without (P:
      0.43). Thus, routine nasogastric decompression neither prevented the development
      of gastrointestinal discomfort nor precluded the need for tube replacement once
      it was discontinued. For every patient who required post-operative nasogastric
      decompression, at least 14 patients were spared one. Mean hospital stay was
      significantly more in the decompressed group (7.52 days; correlation coefficient:
      0.22; P<0.05). CONCLUSION: This study has shown that the prophylactic nasogastric
      decompression following emergency laparotomy is ineffective in achieving any of
      the intended goals. KEYWORDS: complications; decompression; emergency laparotomy;
      flatus; nasogastric tube; prophylactic.

PMID- 24907947
TI  - Complementary feeding practices of Nepali mothers for 6 months to 24 months
      children.
AB  - INTRODUCTION: Lack of knowledge and proper feeding practices contribute to higher
      childhood morbidity and mortality. The aim of the study was to evaluate the
      mother's knowledge and practices in terms of quantity, quality and timing of
      complementary feeding in infant and young child. METHODS: A hospital based cross
      sectional study was conducted between June, 2010 to October, 2011, at Kanti
      Children's Hospital, Nepal, involving 1100 mothers of children from 6 to 24
      months of age who attended outpatient department of this hospital, applying
      systematic sampling technique using semi-structured questionnaire. RESULTS:
      Eighty-seven percent of mothers had knowledge about the duration of exclusive
      breast feeding but only 33.0% practiced it and 21.0% breast fed their children up
      to 3 months. Eighty-seven percent of mothers knew when to start complementary
      feeding and 53.27% of mothers used the marketed weaning food. lito alone was
      offered by 28.27% as complementary food. Though 36.6% had proper knowledge of
      frequency of complementary feeding, only 33.27% were actually practicing it and
      9.9% were offering more frequent than recommended. About half of the mothers fed
      their child with the food of appropriate consistency and 66.0% fed with the
      appropriate amount. But only 15.82% mothers fed their children with ideal
      frequency, sufficient amount and ideal quality. CONCLUSIONS: There was a
      knowledge and practice gap of duration of exclusive breast feeding and initiation
      and continuation of ideal complementary feeding. Rate of exclusive breast feeding
      was on declining trend.

PMID- 24907948
TI  - Clinico-pathological study of colorectal carcinoma.
AB  - INTRODUCTION: Colorectal carcinoma (CRC) ranks as the fourth most frequent cancer
      in men (after lung, prostate and stomach cancer), and third in women (after
      cancers of breast and uterine cervix).Adenocarcinoma of the colon is the most
      common malignancy of the GI tract and is a major cause of morbidity and mortality
      worldwide. It is also one of the most common cancers in Nepal. METHODS: A
      descriptive study was conducted in a Kathmandu based Hospital. This study
      included 50 cases of colorectal carcinoma diagnosed on
      colonoscopic/sigmoidoscopic biopsies over a period of two years. RESULTS: A total
      of 50 patients were studied out of these, 29 (58%) patients were male, whereas 21
      (42%) were with male:female ratio of 1.3:1. Age ranged was from 20 years to 80
      years. Maximum number of cases were observed between the ages of 61-70 years. The
      most common histological type of colorectal carcinoma was moderately
      differentiated adenocarcinoma and seen in 37(74%) cases. Left sided tumor
      constituted 40 (80%) cases of all tumors and rectum was the predominant site with
      26 (52%) cases followed by sigmoid colon with 7 (14%) cases. CONCLUSIONS:
      Colorectal carcinoma (CRC) is not an uncommon disease in this part of the world.
      The use of sigmoidoscopy and colonoscopy along with biopsy when required should
      be encouraged as a screening program for colorectal carcinoma in an elderly age
      group for the detection of CRC at an earlier stage.

PMID- 24907949
TI  - Correlation of severity of ST segment elevation with respect to the site of right
      coronary artery lesion.
AB  - INTRODUCTION: Electrocardiogram a widely available tool may predict infarct
      related artery in acute inferior wall myocardial infarction. Severity of ST
      segment elevation may correlate with proximity of lesion in right coronary
      artery. METHODS: Patient with acute ST segment elevation inferior wall myocardial
      infarction who underwent coronary angiogram was studied. Differences in
      electrocardiogram among right coronary and left circumflex groups were evaluated.
      Severity of ST segments elevation in relation to site of lesion in right coronary
      was studied. RESULTS: The mean age of presentation was 59.52 +/- 11.01 years.
      Total 36 (72%) were men. A total of 42 (84%) had lesion in right and 8 (16%) in
      left circumflex. Age, sex,diabetes,hypertension, smoking, dyslipidemia and
      physical activity showed no correlation with lesion in right or circumflex
      coronary artery. ST segment elevation in III>II (P=0.01), ST segment depression
      in AVL> I (P<0.01) and ST elevation in V4R (P=0.04), correlated with right
      coronary lesion. Sum of ST elevation in inferior leads were 10.90 +/-1.30 mm for
      proximal, 7.38+/-1.19 mm for mid and 5.50+/- 0.53 mm for distal right coronary
      with significant correlation (P<0.01). CONCLUSIONS: Electrocardiogram was
      reliable tool to difference right and left circumflex lesion. Severity of sum of
      ST segment elevations in inferior leads correlated with the proximity of lesion
      in right coronary.

PMID- 24907950
TI  - Emotional and behavioural problems among sheltered homeless children.
AB  - INTRODUCTION: Homelessness in children is a serious problem in the society.
      Factors leading to homelessness in Nepalese children are poverty, unemployment,
      multiple children, exposure to violence, caste based social discrimination etc.
      Children living out of their homes have problems in attachment, temperament,
      social skills, cognitive ability, and language development. Few non-governmental
      organizations that have started to look after these children but the mental
      health need is neglected. The study attempted to investigate the emotional and
      behavioural problems in homeless children in one of the shelters in Kathmandu.
      METHODS: All the children (n=126) in the SAATHI Organization were included in the
      study. They were administered Child Behaviour Check List 6-18. Children with T
      score >=65 on externalising or internalising dimension were further evaluated in
      the Child Guidance Clinic for the final diagnosis based on DSM IV. RESULTS: The
      prevalence of emotional and behavioural problem among the participants was 36
      (28.57%) [15 (26.31%) in boys and 21 (30.43%) in girls] based on CBCL/6-18 years
      and 29 (23.01%) [12 (21.05%) in boys and 17 (24.63%) in girls] based on final
      diagnosis. The conduct problems was the most common among the male children 5
      (8.77%), followed by ODD 3 (5.26%), ADHD 2 (3.5%), Anxiety 2 (3.50%) whereas
      Anxiety is most common in female children 9 (13.04 %), followed by depression 5
      (7.24%), conduct 3 (4.34%). CONCLUSIONS: The rate of emotional and behavioral
      disorder in homeless children in the study is similar to the school aged non
      homeless children in previous studies, which may be because of the protection
      provided by the shelters. This study highlighted the need for methodologically
      better studies in the field.

PMID- 24907951
TI  - Detection of abnormal cervical cytology in papanicolaou smears in a tertiary care
      center.
AB  - INTRODUCTION: Cancer of uterine cervix is a leading cause of mortality and
      morbidity among women worldwide. In developing countries it is the most common
      gynaecological cancer and one of the leading causes of cancer death among women.
      Pap smears are commonly used as cytological screening test for successful
      eradication of precancerous lesions, which has made it a routine procedure
      worldwide. METHODS: This descriptive study was conducted at Kathmandu Medical
      College Teaching Hospital, Kathmandu within a period of two years from January
      2011 to December 2012. A total of 1369 cases were screened. RESULTS: In this
      study, cytological examination of the smears showed 944 (68.95%) inflammatory
      smears, 301(21.99%) normal smears, 101(7.38%) atrophic smears, seven (0.51%)
      ASCUS, two (0.15%) LSIL, four (0.29%) HSIL and two (0.15%) squamous cell
      carcinoma. Radiation changes were seen in three (0.22%) cases. Of all the smears
      studied five (0.36%) cases were inadequate. Regarding ethnicity, incidence of
      epithelial cell abnormalities was high in Tamang (5 cases). Eleven cases (73.33%)
      of epithelial cell abnormalities were seen in patients from urban areas.
      CONCLUSIONS: In country like Nepal with predominant rural population, screening
      and awareness programs with co-operation of media, non-government organizations
      and government should be formulated for early detection of cervical cancer.

PMID- 24907952
TI  - Situation analysis of patients attending TU Teaching Hospital after medical
      abortion with problems and complications.
AB  - INTRODUCTION: In Nepal medical abortion has been approved for use since 2009.
      There were many cases coming to Tribhuvan University Teaching Hospital coming
      with problems and complications following medical abortion. Thus the objective of
      this study was to analyze the cases that came to TUTH following medical abortion
      with problems and complications. METHODS: This is a prospective study conducted
      in the Department of Obstetrics and Gynecology of TUTH. Study was carried from
      1st August 2011 to 30th November 2012. Women who came to TUTH with any complaints
      following medical abortion were interviewed, examined and treatment provided.
      Relevant clinical finding were noted. RESULTS: There were a total of 57 cases
      during the study. Most (66.6%) of the women were in age group 20-29 years age.
      There were 45 (79%) women who had abortion up to 9 weeks. Medical shop was the
      main place where most of the women (45.6%) directly come to know about medical
      abortion. More than 34 (77.2%) received the service from medical shops without
      any supervision. Most 31 (54.4%) presented with incomplete abortion. There were
      three cases of continuing pregnancy and four presented with ectopic pregnancy.
      Eighteen (31.6%) cases needed admission. Fifty six percent of the cases were
      treated with manual vacuum aspiration, six cases underwent laparotomy and there
      was one maternal mortality. CONCLUSIONS: There is a need for proper dissemination
      and implementation of guideline for management of these women and adequate
      supervision to reduce the problems and complications.

PMID- 24907953
TI  - Tuberculosis in HIV patient.
AB  - INTRODUCTION: Strict monitoring ofanti tuberculosis therapy and antiretroviral
      therapyis crucial for proper management of TB/HIV co-infected patients. METHODS:
      Between December 2006 and December 2008 a prospective observational study was
      conducted among 135 TB/HIV co-infected patients visiting antiretroviral therapy
      in Seti Zonal Hospital, Dhangadi. The diagnosed TB patients were subjected to ATT
      through directly observed treatment short-course (DOTS) and its response was
      evaluated as per WHO guidelines. RESULTS: Among 135 studied subjects, 97 (71.9%)
      were males and over 119 (88 %) of the patients were in the age group 21 to 50. Of
      the total TB cases 92 (68.1%) presented pulmonary TB and 37.20% of the Extra
      pulmonary Tuberculosis cases were lymph node TB. 72 (53.33%) of them had
      completed ATT, 11 (8.2%) transfer out and 17 (12.6%) were default. CONCLUSIONS:
      Majority of the patients presented PTB, and lymph node TB was found to be the
      most common EPTB. Comparatively, high efficacy of ATT was found in HIV patients
      visiting this resource poor setting.

PMID- 24907954
TI  - Urothelial tumours of the urinary bladder: a histopathological study of
      cystoscopic biopsies.
AB  - INTRODUCTION: Bladder tumours constitute one of the most common urological
      conditions. Urothelial (transitional cell) carcinoma accounts for 90% of all
      primary tumours of the bladder. These tumours are an important cause of morbidity
      and mortality. The objective of this study was to present the histopathological
      patterns of urothelial tumours and to determine the grade and stage of these
      tumours. METHODS: This is a 3 year descriptive study of urothelial tumours
      carried out in the Department of Pathology, Patan Academy of Health Sciences
      (PAHS), Lalitpur, Nepal. Data of all cystoscopic biopsies collected during this
      period were analyzed. RESULTS: Of the 83 urinary bladder tumours, 81 (97.59%)
      cases were urothelial (transitional cell) tumours. Transitional cell carcinoma
      (TCC) was the most common bladder tumour which was seen in 67 (80.72%) cases.
      Thirty two (47.76%) cases of TCC were low grade while 35 (52.24%) were high
      grade. Forty three (64.18%) cases of TCC were superficial or in early stage (pTa
      and pT1) while 24 (35.82%) showed muscle invasion. CONCLUSIONS: Transitional cell
      carcinoma was the most common bladder cancer. Most of these tumours were high
      grade. A large percentage of high grade carcinomas presented with muscle
      invasion. Pathological grade and muscle invasion are the most valuable prognostic
      predictors of survival. The importance of including smooth muscle in the biopsy
      specimens needs to be emphasized.

PMID- 24907956
TI  - Clinico-radiological aspects of neurocysticercosis in pediatric population in a
      tertiary hospital.
AB  - INTRODUCTION: Neurocysticercosisis common in developing countries including
      Nepal. Clinicalpresentations vary depending on the CT scan findings of head.
      Adequate information of neurocysticercosis in children from Western Nepal is
      lacking. This study was conducted with an objective of evaluating the most common
      clinical and radiological picture in children suffering from NCC at a tertiary
      care teaching hospital in Western Nepal. METHODS: Hospital records of all
      pediatric inpatients, admitted from 16th June 2010 to 15th December 2012,
      consistent with the diagnosis of Neurocysticercosis were reviewed. RESULTS: Forty
      nine cases of neurocysticercosis were enrolled. Their age varied 2.6 years to 14
      years with the mean age of 10.6 years and the peak age was at 12 years with
      slight male predominance, ratio being male:female 1.2:1. The commonest
      presentation was seizures (n=38; 77.5 %); partial seizures being most common.
      Most of the lesions were single (n=44; 89.8%), predominantly in the parietal
      region (n=20; 40.8%) and most were in transitional stage (61.22%) in Computed
      tomography (CT).However, number of lesions from CT scan of head showed no
      significance in association with seizure types (p=0.84). In addition,
      perilesional edema and scolex within the lesion were noted in 67.34% and 18.36%
      of the cases respectively. CONCLUSIONS: Any child presenting with acute onset of
      afebrile seizure should be screened for neurocysticercosis provided other common
      infective and metabolic causes are ruled out. CT scan is the valuable diagnostic
      tool to support our diagnosis.

PMID- 24907955
TI  - Assessment of risk factors against severity of COPD in non-smokers.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease in non-smokers has been an
      important concern in past decade. We studied the risk factors responsible for
      more severe Chronic obstructive pulmonary disease. Identifying them would help to
      work against progression to more severe disease as well as prevention. METHODS: A
      prospective cross sectional study was done in outpatient clinic of Jinnah
      postgraduate medical center from December 2010 to December 2011. All patients
      fulfilling the criteria for Chronic obstructive pulmonary disease were taken in
      study. Patients with less than five pack years smoking with other risk factors
      for Chronic obstructive pulmonary disease were evaluated. RESULTS: Out of total
      90 patients, 74 (82.2%) had mild chronic obstructive pulmonary disease and 16
      (17.7%) had moderate to severe chronic obstructive pulmonary disease. Patients
      with single biomass exposure were found to have mild chronic obstructive
      pulmonary disease except those having mosquito coil exposure. Patients with
      mosquito coil and wood smoke exposure were observed to have moderate to severe
      chronic obstructive pulmonary disease (p-value 0.009). CONCLUSIONS: Wood smoke
      with mosquito coil smoke exposure is responsible for more severe chronic
      obstructive pulmonary disease.

PMID- 24907957
TI  - Gastric cancer perforation: experience from a tertiary care hospital.
AB  - INTRODUCTION: Gastric cancer perforation can occurs in advanced stage of the
      disease and is often associated with a high morbidity and mortality. Peritonitis
      due to perforation needs emergency laparotomy and different surgical procedures
      can be performed for definitive treatment. Surgical procedures largely depend on
      the stage of the disease and general condition of the patient. This study was
      carried out to evaluate the outcome and role of different surgical procedures in
      gastric cancer perforation. METHODS: Medical record of patients with gastric
      perforation, who were treated during ten years period, was reviewed
      retrospectively. Data regarding clinical presentation, surgical procedures,
      staging and survival of patients were obtained. RESULTS: Features suggestive of
      diffuse peritonitis were evident in all cases. The majority of the patients
      underwent emergency surgery except one who died during resuscitation. The
      majority of patients were in stage III and stage IV. Surgical procedure includes
      simple closure and omental patch in five patients, simple closure and
      gastrojejunostomy in nine patients, gastrectomy in six patients and Devine's
      antral exclusion in one patient. Surgical site infection was the most common
      (45.5%) postoperative complication. Four patients died within one month of the
      surgery. Three patients who underwent gastrectomy survived for one year and one
      patient survived for five years. CONCLUSIONS: Although gastric cancer perforation
      usually occurs in advanced stage of the disease, curative resection should be
      considered as far as possible.

PMID- 24907958
TI  - A cadaveric study of different angles of scapula and their role in kinesiometrics
      and muscle morphology.
AB  - INTRODUCTION: The bipedal gait and consequential freedom of the upper limb in
      human beings has made the movements of the shoulder joint a subject of extensive
      investigations. The scapular angles provide the base and leverage to various
      muscles and have been correlated with the different movements of the shoulder
      joint. METHODS: In the present study, different angles of scapula namely
      superior, inferior, lateral, medial, acromial and coracoid angles were measured
      in the North Indian population. The study was conducted on 100 scapulas
      (R:L=50:50) obtained from Department of Anatomy, Government Medical College,
      Amritsar. For measuring the angles, centimetre scales and protractor were used.
      RESULTS: The mean value of superior angle was observed to be 100.830 (R=100.320 :
      L=101.340); inferior angle was 63.620 (R=68.10:L=59.140); lateral angle was
      61.720 (R=65.90 : L=57.540); medial angle was 147.640 (R=151.320 : L=143.960);
      acromial angle was 106.470 (R=107.680 : L=105.260) and coracoid angle was 83.30
      (R=84.240:L=82.020). CONCLUSIONS: It was observed that all angles were higher in
      the right sided bones except superior angle. Also a wide range was seen in all
      the angles.

PMID- 24907960
TI  - A rare malignant transformation of benign lacrimal tumor.
AB  - Lacrimal gland tumors are common in middle age group individuals. Proptosis is
      one of their common presentations. Sometimes the tumors may undergo malignant
      changes which if neglected can be life threatening. Here we present a case of 49
      years male with gradual painless protrusion and diminution of vision in his right
      eye for eight years and more since last 2 months, with restriction of ocular
      motility in right lateral gaze. Expecting a benign mass, superolateral orbitotomy
      with excisional biopsy was done which astonishingly revealed carcinoma ex
      pleomorphic adenoma with components of adenocarcinoma and squamous cell carcinoma
      without any lymphovascular invasion. Proptosis and vision of the patient in right
      eye improved post excisional biopsy without any residual mass in respective
      follow ups.

PMID- 24907959
TI  - A comparison of the approaches to assess the abdominal aortic stiffness using M
      mode ultrasonography, tissue tracking and strain rate imaging.
AB  - INTRODUCTION: Which kind of ultrasound imaging technique is suitable for the
      assessment of the abdominal aortic stiffness are seldom reported. The purposes of
      this study were to explore a reliable method to evaluate the abdominal aortic
      stiffness in patients with hypertension among the following ultrasound imaging
      techniques: M-mode ultrasonography (M-mode), tissue tracking and strain rate
      imaging. METHODS: Fifty patients with hypertension and fifty age and sex-matched
      healthy volunteers were involved in this study. The displacement (d), the peak
      strain (epsilon) and the peak strain rate (s) were obtained from the long-axis
      images of the abdominal aorta using tissue tracking and strain rate imaging,
      respectively. The pressure strain elastic modulus (Ep), beta stiffness index and
      distensibility were calculated according to the conventional formulas using M
      mode combined with the blood pressure. RESULTS: Compared to the normal subjects,
      the difference between systolic diameters and diastolic diameters (?diameter),
      the displacement of posterior wall (d-posterior), the difference of the
      displacement between anterior and posterior wall (? displacement), and the
      distensibility decreased and the Ep and beta stiffness index increased in the
      hypertension patients There were no significant differences between the patients
      with hypertension and the normal subjects according to the epsilon, s. Among
      ?diameters, d-posterior, ?displacement, the epsilon and s, only ?diameters
      significantly correlated with the Ep, beta stiffness index and the distensibility
      in hypertension patients. CONCLUSIONS: Strain rate imaging cannot sensitively
      discriminate the difference of the abdominal aortic stiffness between patients
      with hypertension and the normal subjects. M-mode ultrasonography is still a
      classical method for accessing the aortic elasticity.

PMID- 24907961
TI  - Rare location of primary non-Hodgkin's lymphoma in the rectum.
AB  - Lymphomas of the gastrointestinal tract are usually secondary. Primary rectal
      lymphoma is very rare by virtue of its location. We present here a 60 years old
      lady diagnosed as primary rectal diffuse large B-cell Non-Hodgkin's lymphoma
      managed operatively. The optimum management of this entity is still much debated.

PMID- 24907962
TI  - Anomalous origin of the coronary arteries: an account of six cases.
AB  - Anomalous origin of coronary arteries is a rare type of congenital anomalies with
      a low incidence. It is considered an incidental finding without clinical
      significance, however, these abnormalities may be responsible for angina
      pectoris, heart failure, arrhythmias and increased risk of sudden death. In this
      paper, six cases that were diagnosed with anomalous origin of coronary arteries
      confirmed by coronary angiography has been described and also briefly reviewed
      the literature concerning current views and therapy of this abnormality.

PMID- 24907964
TI  - Paratesticular leiomyosarcoma: a case report.
AB  - Paratesticularleiomyosarcomas are rare neoplasms. Radical orchidectomy and high
      ligation of cord followed by surveillance is the treatment of choice. Here we
      report a 73-year-old man who presented with a 2-year history of painless lump in
      the left hemiscrotum. A left radical orchiectomy with high ligation of the
      spermatic cord was performed. The histo-pathological and immunohistochemistry
      evaluation revealed a moderately differentiated leiomyosarcoma of paratesticular
      region. The patient is still alive with no evidence of local recurrence and
      distant metastasis after seven years of follow-up.

PMID- 24907963
TI  - Desmoplastic ameloblastoma of the mandible.
AB  - The Desmoplastic Ameloblastoma exhibits important differences in anatomical
      distribution, histologic appearance and radiographic findings compared with the
      classic type of ameloblastoma. We describe a case of desmoplastic variant of
      ameloblastoma localized in the mandibular anterior portion of the jaw, extending
      posteriorly in the left side. The tumor was expansile, slowly growing and
      painless. The radiographic finding showed diffuse, radiolucent lesion with
      cortical bone expansion. Surgical excision was performed and follow-up
      examination done after two years disclosed no recurrence. The purpose of this
      article is to assist in better understanding of this variant of odontogenic
      tumor.

PMID- 24907965
TI  - Idiopathic epiretinal membrane in young patient: a rare case presentation.
AB  - Epiretinal membrane is avascular fibrous tissue which is adhered to the internal
      layers of retina in the macular area. Patient may be asymptomatic or present with
      blurring of vision and metamorphopsia. The idiopathic Epiretinal Membrane is more
      often seen in elderly but it could be present in young patients in association
      with other vitreo-retinal diseases and following intraocular surgery. The
      idiopathic Eperetinal Membrane in young patients are rare. Here we present a
      thirty one year healthy women presented with idiopathic Epiretinal Membrane who
      gained full visual recovery following the pars plana vitrectomy, membrane peeling
      and gas for its rarity.

PMID- 24907966
TI  - Sleep induced hypoxemia in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease is a leading cause of morbidity and
      mortality worldwide. Sleep-induced hypoxemia is defined as "an SpO2
      (oxyhemoglobin saturation) during sleep of < 90% for more than five minutes with
      a nadir of at least 85%" or "> 30% of total sleep time with an SpO2 of < 90%" in
      subject with a baseline awake SpO2 of >= 90%. Patients with moderate or severe
      COPD run a high risk of developing SIH mainly because of alveolar hypoventilation
      and ventilation-perfusion mismatch. Compared to their non-SIH brethren, SIH COPD
      patients have greater degrees of pulmonary hypertension and cor pulmonale,
      require more frequent hospitalizations, and sustain higher mortality rates. And
      the necessity of treatment of isolated SIH in COPD has been debated for years. In
      this mini review, the definition, reasons, prevalence, clinical significance and
      treatment approaches of SIH in COPD are summarized.

PMID- 24907967
TI  - Rotavirus, vaccine and unanswered questions: a perspective from a least developed
      country.
AB  - Two rotavirus vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline) have been
      developed to neutralize the most common rotavirus serotypes, and are now
      available in the global market. These vaccines are primarily aimed at reducing
      rotavirus gastroenteritis in children in the least developed countries, where
      rotavirus mortality rate is believed to be greatest. Thus, the World Health
      Organization (WHO) has recommended rotavirus vaccination be included in all
      national immunization programs, while the least developed countries have so far
      not come up with clear vision and long term strategy on vaccine implementation,
      and several questions, in addition to this, remain unanswered.

PMID- 24907968
TI  - Mobile phone support for rural health workers in Nepal through 'celemedicine'.
AB  - Globally, there is a shortage of health workers in rural areas. Effective health
      systems depend on having sufficient, accessible health workers with the right
      skills. In countries like Nepal, highly skilled health workers often prefer to
      work overseas or in urban centres, and therefore, in the short term, it may be
      pragmatic to focus on ensuring support and skills development of mid level or
      paramedical health workers. Information technology has the potential to support
      these health workers. We describe a pilot intervention undertaken in Gulmi
      District, whereby all mid level health workers in the district have been provided
      with a free phone number to call three General Practitioner Doctors (GPs) in the
      District Hospital. The intervention aims to increase appropriate referral, and
      increase connectivity between the District centre and peripheral health
      facilities. We hope that our intervention will provide support to rural health
      workers, and, if implemented as part of a package of interventions, may increase
      retention. We present some initial findings from discussions with health workers
      and analysis of call-log data, and describe our next phase evaluation and
      possible scale-up.

PMID- 24907969
TI  - Need of medical education system reform in Nepal.

PMID- 24907970
TI  - Metastable excited states of OBr2- and OCl2- dianions.
AB  - Electronic stabilities, structures, properties, and spectroscopic constants of
      the halogen oxide dianions OBr2- and OCl2- and their singly charged anions which
      are of astrophysical and laboratory interests have been studied. The X2Sigma
      states of OBr2- and OCl2- are metastable with PECs having smooth wells with
      minima located at R=1.859 A and 1.776 A, and Coulomb barriers of 40402.54987 cm(
      1) and 43746.63462 cm(-1) heights located at RRCB=2.100 A and 1.922 A,
      respectively, both without any vibrational states. While, the B2Sigma state of
      OBr2- and the A2Sigma state of OCl2- are metastable with PECs having wells deep
      enough to suite several bound states, with minima located at Re=1.773 A and
      1.6430 A, and Coulomb barriers of 191437.45813 cm(-1) and 180550.70294 cm(-1)
      heights located at RRCB=2.658 A and 2.4480 A, with De=1.26470 eV and 1.60837 eV,
      respectively. The OBr- and OCl- singly charged anions are stable in their ground
      states. Based on the calculated Frank-Condon factors, it is concluded that
      metastable excited state OBr2- and OCl2- dianions and ground state OBr- and OCl-
      singly charged anions can be formed via electron capture processes.

PMID- 24907971
TI  - Photophysical properties of Schiff's bases from 3-(1,3-benzothiazol-2-yl)-2
      hydroxy naphthalene-1-carbaldehyde.
AB  - A series of novel Schiff's bases have been synthesized from 3-(1,3-benzothiazol-2
      yl)-2-hydroxynaphthalene-1-carbaldehyde. The presence of hydroxyl group ortho to
      the benzothiazolyl group as well as the imine linkage lead to the occurrence of
      excited state intramolecular proton transfer process. The computational strategy
      was used to study the ESIPT process of the synthesized Schiff's bases, which
      revealed surprisingly that the keto form predominantly exists in the ground state
      contradicting the ESIPT process. Density functional theory and time dependent
      density functional theory have been used to investigate the structural parameters
      and photophysical properties in different solvents of one of the Schiff's bases.
      The experimental results correlate well with the computed results. All Schiff's
      bases show good thermal stability. 

PMID- 24907972
TI  - Biosynthesis of Ag nanoparticles using pedicellamide and its photocatalytic
      activity: an eco-friendly approach.
AB  - The synthesis of silver (Ag) nanoparticles using by pedicellamide (A), isolated
      from Piper pedicellatum C.DC leaf is demonstrated here. TEM analysis revealed
      that the Ag nanoparticles predominantly form spherical in shape. The compound 'A'
      act as a reducing, stabilizing and capping agent. The reaction mechanism was
      established by using density functional theory (DFT). Photocatalytic property of
      the Ag nanoparticles is investigated by degradation of Methyl Red (MR) dye under
      UV light. The kinetic, reaction mechanism and rate constant of photocatalytic
      degradation of MR was evaluated. The results show that Ag nanoparticles have
      suitable photocatalytic activity for the degradation of MR dye. 

PMID- 24907973
TI  - Synthesis, characterization, solvatochromism and biological properties of 2,2'
      ((1E,1'E)-((1,2,5-oxadiazole-3,4-diyl)bis (azanylylidene))bis(methan
      ylylidene))bis(4-(phenyldiazenyl)phenol).
AB  - Azo-azomethine dyes 2-((4-amino-1,2,5-oxadiazol-3-ylimino)methyl)-4-(phenyl
      diazenyl)phenols (2a-h) have been synthesized by condensation reaction of 3,4
      diamino-1,2,5-oxadiazole with 2-hydroxy-5-[(E)-(aryldiazenyl)]benzaldehyde (1a-h)
      in methanol. The structures of dyes have been characterized by elemental
      analysis, mass, IR, UV-Vis, 1H and 13S NMR spectroscopy. UV-Vis absorption
      spectra indicated enol-keto tautomeric and positive solvatochromism in compounds
      2a-h which is dependent on the substitution, solvent, pH and environment
      temperature. The synthesized compounds were investigated for their in vitro
      antioxidant activity by diphenylpicrylhydrazyl assay. Compounds substituted with
      electron donating groups, such as, alkyl and methoxy groups showed moderate
      antioxidant activity. The in vitro antibacterial activity of all compounds was
      determined by disk diffusion method. The test compounds showed varying degree of
      inhibition against B. cereus and S. aureus strains.

PMID- 24907975
TI  - Age-related differences in the availability of visual feedback during bimanual
      pinch.
AB  - PURPOSE: Previous research has indicated that older adults have significantly
      lower accuracy in terms of force control than young adults. In addition, accuracy
      of force control is known to decrease in the absence of visual feedback. However,
      whether the effect of visual feedback on fine motor control is similar for young
      adults and older adults is not clear. The purpose of this study, therefore, was
      to examine the effect of visual feedback on bimanual pinch force control in older
      adults. METHODS: Thirty-one undergraduate students (age 19.7 +/- 0.9 years) and
      31 older adults (age 65.1 +/- 8.1 years) participated in this study. After
      measuring finger-pinch maximal voluntary force (MVF), the participants were asked
      to maintain 10% MVF as steadily as possible in two different conditions: with
      visual feedback (visual feedback condition; VF condition) and without visual
      feedback (no visual feedback condition; NVF condition). RESULTS: We found that
      older adults had significantly greater targeting error and force variability than
      young adults in the VF condition, but not in the NVF condition. In addition,
      older participants exhibited a significantly greater sum of power for the 0-4 and
      4-8 Hz frequency bin than young adults (p < 0.05) in the VF condition, although
      there was no significant difference in the NVF condition. CONCLUSIONS: These
      results suggest that older adults do not use visual information as effectively as
      younger adults to reduce force control error.

PMID- 24907974
TI  - Influence of acute exercise of varying intensity and duration on postprandial
      oxidative stress.
AB  - INTRODUCTION: Aerobic exercise can reduce postprandial lipemia, and possibly
      oxidative stress, when performed prior to a lipid-rich meal. PURPOSE: To compare
      the impact of acute exercise on postprandial oxidative stress. METHODS: We
      compared aerobic and anaerobic exercise bouts of different intensities and
      durations on postprandial blood triglycerides (TAG), oxidative stress biomarkers
      (malondialdehyde, hydrogen peroxide, advanced oxidation protein products), and
      antioxidant status (trolox equivalent antioxidant capacity, superoxide dismutase,
      catalase, glutathione peroxidase). Twelve trained men (21-35 years) underwent
      four conditions: (1) No exercise rest; (2) 60-min aerobic exercise at 70% heart
      rate reserve; (3) five 60-s sprints at 100% max capacity; and (4) ten 15-s
      sprints at 200% max capacity. All exercise bouts were performed on a cycle
      ergometer. A high-fat meal was consumed 1 h after exercise cessation. Blood
      samples were collected pre-meal and 2 and 4 h post-meal and analyzed for TAG,
      oxidative stress biomarkers, and antioxidant status. RESULTS: No significant
      interaction or condition effects were noted for any variable (p > 0.05), with
      acute exercise having little to no effect on the magnitude of postprandial
      oxidative stress. CONCLUSION: In a sample of healthy, well-trained men, neither
      aerobic nor anaerobic exercise attenuates postprandial oxidative stress in
      response to a high-fat meal.

PMID- 24907976
TI  - Ferrocene and (arene)ruthenium(II) complexes of the natural anticancer
      naphthoquinone plumbagin with enhanced efficacy against resistant cancer cells
      and a genuine mode of action.
AB  - A series of ferrocene and (arene)ruthenium(II) complexes attached to the
      naturally occurring anticancer naphthoquinones plumbagin and juglone was tested
      for efficacy against various cancer cell lines and for alterations in the mode of
      action. The plumbagin ferrocene and (p-cymene)Ru(II) conjugates 1c and 2a
      overcame the multi-drug drug resistance of KB-V1/Vbl cervix carcinoma cells and
      showed IC50 (72 h) values around 1 MUM in growth inhibition assays using 3-(4,5
      dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT). They were further
      investigated for their influence on the cell cycle of KB-V1/Vbl and HCT-116 colon
      carcinoma cells, on the generation of reactive oxygen species (ROS) by the latter
      cell line, for their substrate character for the P-glycoprotein drug eflux pump
      via the calcein-AM efflux assays, and for DNA affinity by the electrophoretic
      mobility shift assay (EMSA). The derivatives 1c and 2a increased the number of
      dead cancer cells (sub-G0/G1 fraction) in a dose- and time-dependent manner. ROS
      levels were significantly increased upon treatment with 1c and 2a. These
      compounds also showed a greater affinity to linear DNA than plumbagin. While
      plumbagin did not affect calcein-AM transport by P-glycoprotein the derivatives
      1c and 2a exhibited a 50% or 80% inhibition of the P-glycoprotein-mediated
      calcein-AM efflux relative to the clinically established sensitizer verapamil.

PMID- 24907977
TI  - Factor structure of the Arthritis-Related Health Belief instrument in ethnically
      diverse community-dwelling older adults with chronic pain.
AB  - Nonpharmacological treatment of chronic pain in older people can be effective but
      attitudes and adherence to use of this treatment may differ by ethnicity. This
      study supports that a modified 14-item instrument based on the modified Health
      Belief Model-the arthritis-related health belief instrument (AHBI)-can be used
      across ethnically diverse older adults (i.e., European Americans, Hispanics,
      African Americans, and Afro-Caribbeans). Confirmatory factor analysis tested the
      factor structure of the AHBI to eliminate items inappropriate for this
      population. Structural equation modeling tested expected relationships among four
      latent variables-severity, susceptibility, barriers, and benefits-across the four
      ethnic groups. Findings suggest that the modified 14-item AHBI (eliminating two
      items from the original AHBI) adequately described the four latent factors
      pertaining to use of nonpharmacological pain therapy in this sample. All items
      registered substantial loadings (.41-.95) on the hypothesized factors, operating
      similarly across the four ethnic groups. The modified 14-item AHBI may be useful
      in (a) assessing how individual perceptions influence access to
      nonpharmacological pain therapy among ethnically diverse community-dwelling older
      adults, with the goal to develop and implement effective pain treatment for this
      population; and (b) measuring the likelihood of using nonpharmacological pain
      therapy by older adults. The modified 14-item AHBI can help health care providers
      to provide accurate pain assessment and examine domains that could affect use of
      nonpharmacological pain therapy by ethnically diverse older adults and guide
      practice with them by identifying barriers to use of such therapies and providing
      education to encourage their use. 

PMID- 24907979
TI  - MicroRNA-155 and macrophages: a fatty liaison.

PMID- 24907978
TI  - Macrophage activation state determines the response to rhinovirus infection in a
      mouse model of allergic asthma.
AB  - BACKGROUND: The mechanisms by which viruses cause asthma exacerbations are not
      precisely known. Previously, we showed that, in ovalbumin (OVA)-sensitized and 
      challenged mice with allergic airway inflammation, rhinovirus (RV) infection
      increases type 2 cytokine production from alternatively-activated (M2) airway
      macrophages, enhancing eosinophilic inflammation and airways hyperresponsiveness.
      In this paper, we tested the hypothesis that IL-4 signaling determines the state
      of macrophage activation and pattern of RV-induced exacerbation in mice with
      allergic airways disease. METHODS: Eight week-old wild type or IL-4 receptor
      knockout (IL-4R KO) mice were sensitized and challenged with OVA and inoculated
      with RV1B or sham HeLa cell lysate. RESULTS: In contrast to OVA-treated wild-type
      mice with both neutrophilic and eosinophilic airway inflammation, OVA-treated IL
      4R KO mice showed increased neutrophilic inflammation with few eosinophils in the
      airways. Like wild-type mice, IL-4R KO mice showed OVA-induced airway
      hyperreactivity which was further exacerbated by RV. There was a shift in lung
      cytokines from a type 2-predominant response to a type 1 response, including
      production of IL-12p40 and TNF-alpha. IL-17A was also increased. RV infection of
      OVA-treated IL-4R KO mice further increased neutrophilic inflammation.
      Bronchoalveolar macrophages showed an M1 polarization pattern and ex vivo RV
      infection increased macrophage production of TNF-alpha, IFN-gamma and IL-12p40.
      Finally, lung cells from OVA-treated IL-4R KO mice showed reduced CD206+ CD301+
      M2 macrophages, decreased IL-13 and increased TNF-alpha and IL-17A production by
      F4/80+, CD11b+ macrophages. CONCLUSIONS: OVA-treated IL-4R KO mice show
      neutrophilic airway inflammation constituting a model of allergic, type 1
      cytokine-driven neutrophilic asthma. In the absence of IL-4/IL-13 signaling, RV
      infection of OVA-treated mice increased type 1 cytokine and IL-17A production
      from conventionally-activated macrophages, augmenting neutrophilic rather than
      eosinophilic inflammation. In mice with allergic airways inflammation, IL-4R
      signaling determines macrophage activation state and the response to subsequent
      RV infection.

PMID- 24907981
TI  - Communication: Kinetic and pairing contributions in the dielectric spectra of
      electrolyte solutions.
AB  - In the late 1970s, Hubbard and Onsager predicted that adding salt to a polar
      solution would result in a reduced dielectric permittivity that arises from the
      unexpected tendency of solvent dipoles to align opposite to the applied field.
      Here we develop a novel non-equilibrium molecular dynamics simulation approach to
      determine this decrement accurately. Using a thermodynamic consistent all-atom
      force field we show that for an aqueous solution containing sodium chloride
      around 4.8 mol/l, this effect accounts for 12% of the total dielectric
      permittivity. The dielectric decrement can be strikingly different if a less
      accurate force field for the ions is used. Using the widespread GROMOS
      parameters, we observe in fact an increment of the dielectric permittivity rather
      than a decrement, caused by ion pairing and introduced by a too low dispersion
      force. 

PMID- 24907980
TI  - HDL and cholesterol handling in the brain.
AB  - Cholesterol is an essential component of both the peripheral nervous system and
      central nervous system (CNS) of mammals. Brain cholesterol is synthesized in situ
      by astrocytes and oligodendrocytes and is almost completely isolated from other
      pools of cholesterol in the body, but a small fraction can be taken up from the
      circulation as 27-hydroxycholesterol, or via the scavenger receptor class B type
      I. Glial cells synthesize native high-density lipoprotein (HDL)-like particles,
      which are remodelled by enzymes and lipid transfer proteins, presumably as it
      occurs in plasma. The major apolipoprotein constituent of HDL in the CNS is
      apolipoprotein E, which is produced by astrocytes and microglia. Apolipoprotein A
      I, the major protein component of plasma HDL, is not synthesized in the CNS, but
      can enter and become a component of CNS lipoproteins. Low HDL-C levels have been
      shown to be associated with cognitive impairment and various neurodegenerative
      diseases. On the contrary, no clear association with brain disorders has been
      shown in genetic HDL defects, with the exception of Tangier disease. Mutations in
      a wide variety of lipid handling genes can result in human diseases, often with a
      neuronal phenotype caused by dysfunctional intracellular lipid trafficking. 

PMID- 24907982
TI  - Communication: Structure characterization of hard sphere packings in amorphous
      and crystalline states.
AB  - The channel size distribution in hard sphere systems, based on the local neighbor
      correlation of four particle positions, is investigated for all volume fractions
      up to jamming. For each particle, all three particle combinations of neighbors
      define channels, which are relevant for the concept of caging. The analysis of
      the channel size distribution is shown to be very useful in distinguishing
      between gaseous, liquid, partially and fully crystallized, and glassy (random)
      jammed states. A common microstructural feature of four coplanar particles is
      observed in crystalline and glassy jammed states, suggesting the presence of
      "hidden" two-dimensional order in three-dimensional random close packings. 

PMID- 24907983
TI  - Communication: Integral equation theory for pair correlation functions in a
      crystal.
AB  - A method for calculating pair correlation functions in a crystal is developed.
      The method is based on separating the one- and two-particle correlation functions
      into the symmetry conserving and the symmetry broken parts. The conserving parts
      are calculated using the integral equation theory of homogeneous fluids. The
      symmetry broken part of the direct pair correlation function is calculated from a
      series written in powers of order parameters and that of the total pair
      correlation function from the Ornstein-Zernike equation. The results found for a
      two-dimensional hexagonal lattice show that the method provides accurate and
      detailed informations about the pair correlation functions in a crystal. 

PMID- 24907985
TI  - Minima hopping guided path search: an efficient method for finding complex
      chemical reaction pathways.
AB  - The Minima Hopping global optimization method uses physically realizable
      molecular dynamics moves in combination with an energy feedback that guarantees
      the escape from any potential energy funnel. For the purpose of finding reaction
      pathways, we argue that Minima Hopping is particularly suitable as a guide
      through the potential energy landscape and as a generator for pairs of minima
      that can be used as input structures for methods capable of finding transition
      states between two minima. For Lennard-Jones benchmark systems we compared this
      Minima Hopping guided path search method to a known approach for the exploration
      of potential energy landscapes that is based on deterministic mode-following.
      Although we used a stabilized mode-following technique that reliably allows to
      follow distinct directions when escaping from a local minimum, we observed that
      Minima Hopping guided path search is far superior in finding lowest-barrier
      reaction pathways. We, therefore, suggest that Minima Hopping guided path search
      can be used as a simple and efficient way to identify energetically low-lying
      chemical reaction pathways. Finally, we applied the Minima Hopping guided path
      search approach to 75-atom and 102-atom Lennard-Jones systems. For the 75-atom
      system we found pathways whose highest energies are significantly lower than the
      highest energy along the previously published lowest-barrier pathway.
      Furthermore, many of these pathways contain a smaller number of intermediate
      transition states than the previously publish lowest-barrier pathway. In case of
      the 102-atom system Minima Hopping guided path search found a previously unknown
      and energetically low-lying funnel. 

PMID- 24907986
TI  - General coalescence conditions for the exact wave functions. II. Higher-order
      relations for many-particle systems.
AB  - We derived the necessary conditions that must be satisfied by the non
      relativistic time-independent exact wave functions for many-particle systems at a
      two-particle coalescence (or cusp) point. Some simple conditions are known to be
      Kato's cusp condition (CC) and Rassolov and Chipman's CC. In a previous study, we
      derived an infinite number of necessary conditions that two-particle wave
      functions must satisfy at a coalescence point. In the present study, we extend
      these conditions to many-particle systems. They are called general coalescence
      conditions (GCCs), and Kato's CC and Rassolov and Chipman's CC are included as
      special conditions. GCCs can be applied not only to Coulombic systems but also to
      any system in which the interaction between two particles is represented in a
      power series of inter-particle distances. We confirmed the correctness of our
      derivation of the GCCs by applying the exact wave function of a harmonium in
      electron-electron and electron-nucleus coalescence situations. In addition, we
      applied the free complement (FC) wave functions of a helium atom to the GCCs to
      examine the accuracy of the FC wave function in the context of a coalescence
      situation. 

PMID- 24907987
TI  - Collecting high-order interactions in an effective pairwise intermolecular
      potential using the hydrated ion concept: the hydration of Cf3+.
AB  - This work proposes a new methodology to build interaction potentials between a
      highly charged metal cation and water molecules. These potentials, which can be
      used in classical computer simulations, have been fitted to reproduce quantum
      mechanical interaction energies (MP2 and BP86) for a wide range of
      [M(H2O)n](m+)(H2O)l clusters (n going from 6 to 10 and l from 0 to 18). A
      flexible and polarizable water shell model (Mobile Charge Density of Harmonic
      Oscillator) has been coupled to the cation-water potential. The simultaneous
      consideration of poly-hydrated clusters and the polarizability of the interacting
      particles allows the inclusion of the most important many-body effects in the new
      polarizable potential. Applications have been centered on the californium,
      Cf(III) the heaviest actinoid experimentally studied in solution. Two different
      strategies to select a set of about 2000 structures which are used for the
      potential building were checked. Monte Carlo simulations of Cf(III)+500 H2O for
      three of the intermolecular potentials predict an aquaion structure with
      coordination number close to 8 and average R(Cf-O) in the range 2.43-2.48 A,
      whereas the fourth one is closer to 9 with R(Cf-O) = 2.54 A. Simulated EXAFS
      spectra derived from the structural Monte Carlo distribution compares fairly well
      with the available experimental spectrum for the simulations bearing 8 water
      molecules. An angular distribution similar to that of a square antiprism is found
      for the octa-coordination.

PMID- 24907984
TI  - Using Markov state models to study self-assembly.
AB  - Markov state models (MSMs) have been demonstrated to be a powerful method for
      computationally studying intramolecular processes such as protein folding and
      macromolecular conformational changes. In this article, we present a new approach
      to construct MSMs that is applicable to modeling a broad class of multi-molecular
      assembly reactions. Distinct structures formed during assembly are distinguished
      by their undirected graphs, which are defined by strong subunit interactions.
      Spatial inhomogeneities of free subunits are accounted for using a recently
      developed Gaussian-based signature. Simplifications to this state identification
      are also investigated. The feasibility of this approach is demonstrated on two
      different coarse-grained models for virus self-assembly. We find good agreement
      between the dynamics predicted by the MSMs and long, unbiased simulations, and
      that the MSMs can reduce overall simulation time by orders of magnitude. 

PMID- 24907988
TI  - The density matrix functional approach to electron correlation: dynamic and
      nondynamic correlation along the full dissociation coordinate.
AB  - For chemistry an accurate description of bond weakening and breaking is vital.
      The great advantage of density matrix functionals, as opposed to density
      functionals, is their ability to describe such processes since they naturally
      cover both nondynamical and dynamical correlation. This is obvious in the Lowdin
      Shull functional, the exact natural orbital functional for two-electron systems.
      We present in this paper extensions of this functional for the breaking of a
      single electron pair bond in N-electron molecules, using LiH, BeH(+), and Li2
      molecules as prototypes. Attention is given to the proper formulation of the
      functional in terms of not just J and K integrals but also the two-electron L
      integrals (K integrals with a different distribution of the complex conjugation
      of the orbitals), which is crucial for the calculation of response functions.
      Accurate energy curves are obtained with extended Lowdin-Shull functionals along
      the complete dissociation coordinate using full CI calculations as benchmark. 

PMID- 24907989
TI  - Improved initial guess for minimum energy path calculations.
AB  - A method is presented for generating a good initial guess of a transition path
      between given initial and final states of a system without evaluation of the
      energy. An objective function surface is constructed using an interpolation of
      pairwise distances at each discretization point along the path and the nudged
      elastic band method then used to find an optimal path on this image dependent
      pair potential (IDPP) surface. This provides an initial path for the more
      computationally intensive calculations of a minimum energy path on an energy
      surface obtained, for example, by ab initio or density functional theory. The
      optimal path on the IDPP surface is significantly closer to a minimum energy path
      than a linear interpolation of the Cartesian coordinates and, therefore, reduces
      the number of iterations needed to reach convergence and averts divergence in the
      electronic structure calculations when atoms are brought too close to each other
      in the initial path. The method is illustrated with three examples: (1) rotation
      of a methyl group in an ethane molecule, (2) an exchange of atoms in an island on
      a crystal surface, and (3) an exchange of two Si-atoms in amorphous silicon. In
      all three cases, the computational effort in finding the minimum energy path with
      DFT was reduced by a factor ranging from 50% to an order of magnitude by using an
      IDPP path as the initial path. The time required for parallel computations was
      reduced even more because of load imbalance when linear interpolation of
      Cartesian coordinates was used. 

PMID- 24907990
TI  - Energy relaxation and separation of a hot electron-hole pair in organic
      aggregates from a time-dependent wavepacket diffusion method.
AB  - The time-dependent wavepacket diffusive method [X. Zhong and Y. Zhao, J. Chem.
      Phys. 138, 014111 (2013)] is extended to investigate the energy relaxation and
      separation of a hot electron-hole pair in organic aggregates with incorporation
      of Coulomb interaction and electron-phonon coupling. The pair initial condition
      generated by laser pulse is represented by a Gaussian wavepacket with a central
      momentum. The results reveal that the hot electron energy relaxation is very well
      described by two rate processes with the fast rate much larger than the slow one,
      consistent with experimental observations, and an efficient electron-hole
      separation is accomplished accompanying the fast energy relaxation. Furthermore,
      although the extra energy indeed helps the separation by overcoming the Coulomb
      interaction, the width of initial wavepacket is much sensitive to the separation
      efficiency and the narrower wavepacket generates the more separated charges. This
      behavior may be useful to understand the experimental controversy of the hot
      carrier effect on charge separation. 

PMID- 24907991
TI  - Fluctuation-induced transport of two coupled particles: effect of the
      interparticle interaction.
AB  - We consider a system of two coupled particles fluctuating between two states,
      with different interparticle interaction potentials and particle friction
      coefficients. An external action drives the interstate transitions that induces
      reciprocating motion along the internal coordinate x (the interparticle
      distance). The system moves unidirectionally due to rectification of the internal
      motion by asymmetric friction fluctuations and thus operates as a dimeric motor
      that converts input energy into net movement. We focus on how the law of
      interaction between the particles affects the dimer transport and, in particular,
      the role of thermal noise in the motion inducing mechanism. It is argued that if
      the interaction potential behaves at large distances as x(alpha), depending on
      the value of the exponent alpha, the thermal noise plays a constructive (alpha >
      2), neutral (alpha = 2), or destructive (alpha < 2) role. In the case of alpha =
      1, corresponding piecewise linear potential profiles, an exact solution is
      obtained and discussed in detail.

PMID- 24907993
TI  - Molecular dynamics saddle search adaptive kinetic Monte Carlo.
AB  - A method for accelerating molecular dynamics simulations in rare event systems is
      described. From each new state visited, high temperature molecular dynamics
      trajectories are used to discover the set of escape mechanisms and rates. This
      event table is provided to the adaptive kinetic Monte Carlo algorithm to model
      the evolution of the system from state to state. Importantly, an estimator for
      the completeness of the calculated rate table in each state is derived. The
      method is applied to three model systems: adatom diffusion on Al(100); island
      diffusion on Pt(111); and vacancy cluster ripening in bulk Fe. Connections to the
      closely related temperature accelerated dynamics method of Voter and co-workers
      is discussed. 

PMID- 24907992
TI  - Order-parameter-aided temperature-accelerated sampling for the exploration of
      crystal polymorphism and solid-liquid phase transitions.
AB  - The problem of predicting polymorphism in atomic and molecular crystals
      constitutes a significant challenge both experimentally and theoretically. From
      the theoretical viewpoint, polymorphism prediction falls into the general class
      of problems characterized by an underlying rough energy landscape, and
      consequently, free energy based enhanced sampling approaches can be brought to
      bear on the problem. In this paper, we build on a scheme previously introduced by
      two of the authors in which the lengths and angles of the supercell are targeted
      for enhanced sampling via temperature accelerated adiabatic free energy dynamics
      [T. Q. Yu and M. E. Tuckerman, Phys. Rev. Lett. 107, 015701 (2011)]. Here, that
      framework is expanded to include general order parameters that distinguish
      different crystalline arrangements as target collective variables for enhanced
      sampling. The resulting free energy surface, being of quite high dimension, is
      nontrivial to reconstruct, and we discuss one particular strategy for performing
      the free energy analysis. The method is applied to the study of polymorphism in
      xenon crystals at high pressure and temperature using the Steinhardt order
      parameters without and with the supercell included in the set of collective
      variables. The expected fcc and bcc structures are obtained, and when the
      supercell parameters are included as collective variables, we also find several
      new structures, including fcc states with hcp stacking faults. We also apply the
      new method to the solid-liquid phase transition in copper at 1300 K using the
      same Steinhardt order parameters. Our method is able to melt and refreeze the
      system repeatedly, and the free energy profile can be obtained with high
      efficiency. 

PMID- 24907994
TI  - Adiabatic state preparation study of methylene.
AB  - Quantum computers attract much attention as they promise to outperform their
      classical counterparts in solving certain type of problems. One of them with
      practical applications in quantum chemistry is simulation of complex quantum
      systems. An essential ingredient of efficient quantum simulation algorithms are
      initial guesses of the exact wave functions with high enough fidelity. As was
      proposed in Aspuru-Guzik et al. [Science 309, 1704 (2005)], the exact ground
      states can in principle be prepared by the adiabatic state preparation method.
      Here, we apply this approach to preparation of the lowest lying multireference
      singlet electronic state of methylene and numerically investigate preparation of
      this state at different molecular geometries. We then propose modifications that
      lead to speeding up the preparation process. Finally, we decompose the minimal
      adiabatic state preparation employing the direct mapping in terms of two-qubit
      interactions. 

PMID- 24907995
TI  - Block diagonalization of the equation-of-motion coupled cluster effective
      Hamiltonian: treatment of diabatic potential constants and triple excitations.
AB  - We present a diabatization method applicable to spectroscopic studies based on
      Equation-of-Motion Coupled Cluster (EOM-CC) energies and biorthogonal
      wavefunctions that uses the Block Diagonalization (BD) approaches of Cederbaum et
      al. [L. S. Cederbaum, J. Schirmer, and H. D. Meyer, J. Phys. A: Math. Gen. 22,
      2427 (1989)] and Domcke et al. [W. Domcke and C. Woywod, Chem. Phys. Lett. 216,
      362 (1993); W. Domcke, C. Woywod, and M. Stengle, Chem. Phys. Lett. 226, 257
      (1994)]. The method gives excellent agreement with coupling constants calculated
      using the analytic gradient approach of Ichino et al. [T. Ichino, J. Gauss, and
      J. F. Stanton, J. Chem. Phys. 130, 174105 (2009)]. While the BD method is a
      finite difference approach, it can be applied at any geometry, can generate
      (pointwise) diabatic potential energy surfaces, and can be used with EOM
      wavefunctions that include triple (or higher) excitations. The method is applied
      to several model systems and its sensitivity to orbital choice, excitation space,
      and projection space is explored. 

PMID- 24907996
TI  - Seniority zero pair coupled cluster doubles theory.
AB  - Coupled cluster theory with single and double excitations accurately describes
      weak electron correlation but is known to fail in cases of strong static
      correlation. Fascinatingly, however, pair coupled cluster doubles (p-CCD), a
      simplified version of the theory limited to pair excitations that preserve the
      seniority of the reference determinant (i.e., the number of unpaired electrons),
      has mean field computational cost and is an excellent approximation to the full
      configuration interaction (FCI) of the paired space provided that the orbital
      basis defining the pairing scheme is adequately optimized. In previous work, we
      have shown that optimization of the pairing scheme in the seniority zero FCI
      leads to a very accurate description of static correlation. The same conclusion
      extends to p-CCD if the orbitals are optimized to make the p-CCD energy
      stationary. We here demonstrate these results with numerous examples. We also
      explore the contributions of different seniority sectors to the coupled cluster
      doubles (CCD) correlation energy using different orbital bases. We consider both
      Hartree-Fock and Brueckner orbitals, and the role of orbital localization. We
      show how one can pair the orbitals so that the role of the Brueckner orbitals at
      the CCD level is retained at the p-CCD level. Moreover, we explore ways of
      extending CCD to accurately describe strongly correlated systems. 

PMID- 24907997
TI  - Projected seniority-two orbital optimization of the antisymmetric product of one
      reference orbital geminal.
AB  - We present a new, non-variational orbital-optimization scheme for the
      antisymmetric product of one-reference orbital geminal wave function. Our
      approach is motivated by the observation that an orbital-optimized seniority-zero
      configuration interaction (CI) expansion yields similar results to an orbital
      optimized seniority-zero-plus-two CI expansion [L. Bytautas, T. M. Henderson, C.
      A. Jimenez-Hoyos, J. K. Ellis, and G. E. Scuseria, J. Chem. Phys. 135, 044119
      (2011)]. A numerical analysis is performed for the C2 and LiF molecules, for the
      CH2 singlet diradical as well as for the symmetric stretching of hypothetical
      (linear) hydrogen chains. For these test cases, the proposed orbital-optimization
      protocol yields similar results to its variational orbital optimization
      counterpart, but prevents symmetry-breaking of molecular orbitals in most cases. 

PMID- 24907998
TI  - A Brownian dynamics algorithm for colloids in curved manifolds.
AB  - The many-particle Langevin equation, written in local coordinates, is used to
      derive a Brownian dynamics simulation algorithm to study the dynamics of colloids
      moving on curved manifolds. The predictions of the resulting algorithm for the
      particular case of free particles diffusing along a circle and on a sphere are
      tested against analytical results, as well as with simulation data obtained by
      means of the standard Brownian dynamics algorithm developed by Ermak and McCammon
      [J. Chem. Phys. 69, 1352 (1978)] using explicitly a confining external field. The
      latter method allows constraining the particles to move in regions very tightly,
      emulating the diffusion on the manifold. Additionally, the proposed algorithm is
      applied to strong correlated systems, namely, paramagnetic colloids along a
      circle and soft colloids on a sphere, to illustrate its applicability to systems
      made up of interacting particles. 

PMID- 24907999
TI  - When do we need to account for the geometric phase in excited state dynamics?
AB  - We investigate the role of the geometric phase (GP) in an internal conversion
      process when the system changes its electronic state by passing through a conical
      intersection (CI). Local analysis of a two-dimensional linear vibronic coupling
      (LVC) model Hamiltonian near the CI shows that the role of the GP is twofold.
      First, it compensates for a repulsion created by the so-called diagonal Born
      Oppenheimer correction. Second, the GP enhances the non-adiabatic transition
      probability for a wave-packet part that experiences a central collision with the
      CI. To assess the significance of both GP contributions we propose two indicators
      that can be computed from parameters of electronic surfaces and initial
      conditions. To generalize our analysis to N-dimensional systems we introduce a
      reduction of a general N-dimensional LVC model to an effective 2D LVC model using
      a mode transformation that preserves short-time dynamics of the original N
      dimensional model. Using examples of the bis(methylene) adamantyl and butatriene
      cations, and the pyrazine molecule we have demonstrated that their effective 2D
      models reproduce the short-time dynamics of the corresponding full dimensional
      models, and the introduced indicators are very reliable in assessing GP effects. 

PMID- 24908001
TI  - Efficient implementation of the three-dimensional reference interaction site
      model method in the fragment molecular orbital method.
AB  - The three-dimensional reference interaction site model (3D-RISM) method was
      efficiently implemented in the fragment molecular orbital (FMO) method. The
      method is referred to as the FMO/3D-RISM method, and allows us to treat
      electronic structure of the whole of a macromolecule, such as a protein, as well
      as the solvent distribution around a solute macromolecule. The formalism of the
      FMO/3D-RISM method, for the computationally available form and variational
      expressions, are proposed in detail. A major concern leading to the
      implementation of the method was decreasing the computational costs involved in
      calculating the electrostatic potential, because the electrostatic potential is
      calculated on numerous grid points in three-dimensional real space in the 3D-RISM
      method. In this article, we propose a procedure for decreasing the computational
      costs involved in calculating the electrostatic potential in the FMO method
      framework. The strategy involved in this procedure is to evaluate the
      electrostatic potential and the solvated Fock matrix in different manners,
      depending on the distance between the solute and the solvent. The electrostatic
      potential is evaluated directly in the vicinity of the solute molecule by
      integrating the molecular orbitals of monomer fragments of the solute molecule,
      whereas the electrostatic potential is described as the sum of multipole
      interactions when an analog of the fast multipole method is used. The efficiency
      of our method was demonstrated by applying it to a water trimer system and three
      biomolecular systems. The FMO/3D-RISM calculation can be performed within a
      reasonable computational time, retaining the accuracy of some physical
      properties. 

PMID- 24908002
TI  - Evidence for broken ergodicity due to chemical alloying from the dissociation
      kinetics of binary clusters.
AB  - The interplay between thermal relaxation and statistical dissociation in binary
      Morse clusters (AB)N has been investigated using numerical simulations and simple
      statistical approaches, for a variety of interaction parameters covering miscible
      and non-miscible regimes. While all clusters exhibit a core/shell phase
      separation pattern in their most stable, T = 0 structure, different melting
      mechanisms are identified depending on the ranges and their mismatch, including
      two-step melting of the surface and the core or premelting as alloying. The
      preference for emitting A or B particles upon evaporation has been evaluated
      assuming that the cluster is either thermally equilibrated or vibrationally
      excited in its ground state structure, and compared to the predictions of the
      Weisskopf theory. The variations of the dissociation rate constants with
      increasing energy and the branching ratio between the two channels show
      significant differences in both cases, especially when the clusters are miscible
      and bound by short-range forces, which indicates that the time scale for
      evaporation is much shorter than the equilibration time. Our results suggest that
      dissociation properties could be used to test the ergodic hypothesis in such
      compounds. 

PMID- 24908003
TI  - Ground and excited state infrared spectroscopy of jet-cooled radicals: exploring
      the photophysics of trihydronaphthyl and inden-2-ylmethyl.
AB  - The alkyl and aromatic CH stretch infrared spectra of inden-2-ylmethyl (I2M,
      C10H9) and trihydronaphthyl (THN, C10H11) radicals have been recorded under jet
      cooled conditions in the ground (D0) and first electronically excited (D1) states
      using resonant ion-dip infrared (RIDIR) spectroscopy. Previously, the vibronic
      spectroscopy of a series of C10H9 and C10H11 hydronaphthyl radicals were
      investigated and their thermochemical properties were evaluated with isomer
      specificity [J. A. Sebree et al., J. Phys. Chem. A 11, 6255-6262 (2010)]. We show
      here that one of the m/z 129 spectral carriers characterized in that work was
      misidentified as 2-hydronaphthyl (2-HN) radical, appearing in a discharge of 1,2
      dihydronaphthalene in close proximity to 1-hydronaphthyl radical. The D0-RIDIR
      spectrum in the alkyl CH stretch region positively identifies the m/z 129 isomer
      as I2M, whose two-color resonant two-photon ionization (2C-R2PI) spectrum was
      recently reported by Schmidt and co-workers [T. P. Troy et al., Chem. Sci. 2,
      1755-1765 (2011)]. Here, we further characterize the I2M and THN radicals by
      recording their gas phase IR spectra in the alkyl and aromatic CH stretch
      regions, and explore the spectroscopic consequences of electronic excitation on
      the CH stretch absorptions. A local-mode CH stretch Hamiltonian incorporating
      cubic stretch-bend coupling between anharmonic CH stretches and CH2 scissor modes
      is utilized to describe their Fermi resonance interactions. Excellent agreement
      between the experimental and theoretical results facilitates the interpretation
      of the D0- and D1-state RIDIR spectra of I2M, revealing that upon excitation the
      alkyl CH stretches decrease in frequency by 70 cm(-1), while the allyl-like CH
      stretches experience a modest blueshift. In comparison, the photophysics of THN
      are strikingly different in that the IR transitions that possess vibrational
      motion along the CbetaH and CdeltaH bonds are absent in the D1-RIDIR spectrum yet
      are predicted to be present from the theoretical model. Several hypotheses are
      considered to account for the perturbations to these vibrations. 

PMID- 24908000
TI  - Improved parameterization of interatomic potentials for rare gas dimers with
      density-based energy decomposition analysis.
AB  - We examine interatomic interactions for rare gas dimers using the density-based
      energy decomposition analysis (DEDA) in conjunction with computational results
      from CCSD(T) at the complete basis set (CBS) limit. The unique DEDA capability of
      separating frozen density interactions from density relaxation contributions is
      employed to yield clean interaction components, and the results are found to be
      consistent with the typical physical picture that density relaxations play a very
      minimal role in rare gas interactions. Equipped with each interaction component
      as reference, we develop a new three-term molecular mechanical force field to
      describe rare gas dimers: a smeared charge multipole model for electrostatics
      with charge penetration effects, a B3LYP-D3 dispersion term for asymptotically
      correct long-range attractions that is screened at short-range, and a Born-Mayer
      exponential function for the repulsion. The resulted force field not only
      reproduces rare gas interaction energies calculated at the CCSD(T)/CBS level, but
      also yields each interaction component (electrostatic or van der Waals) which
      agrees very well with its corresponding reference value. 

PMID- 24908004
TI  - The effects of two internal rotations in the microwave spectrum of ethyl methyl
      ketone.
AB  - The rotational spectra of ethyl methyl ketone, CH3CH2COCH3, were measured in the
      microwave region from 2 to 40 GHz using two molecular beam Fourier transform
      microwave spectrometers. Splittings due to internal rotations of both, the acetyl
      methyl group -COCH3 and the ethyl methyl group CH3CH2CO-, could be completely
      resolved. All measured transitions were fitted using two different codes, XIAM
      and BELGI-Cs-2Tops. Molecular parameters like the rotational constants and the
      centrifugal distortion constants were determined with very high accuracy. The
      barrier to internal rotation of the acetyl methyl group was fitted to 181.502(98)
      cm(-1), much lower than the value of 763.87(65) cm(-1) found for the ethyl methyl
      group. The splittings in the spectrum due to internal rotation of the acetyl
      methyl group are accordingly much larger, up to 1.2 GHz, whereas for the ethyl
      methyl group only splittings from a few hundreds of kHz up to 4 MHz were
      observed. 

PMID- 24908005
TI  - Reaction dynamics of Al + O2 -> AlO + O studied by a crossed-beam velocity map
      imaging technique: vib-rotational state selected angular-kinetic energy
      distribution.
AB  - Oxidation reaction of a gas-phase aluminum atom by a molecular oxygen was studied
      by a crossed-beam condition at 12.4 kJ/mol of collision energy. A (1+1) resonance
      enhanced multiphoton ionization (REMPI) via the D(2)Sigma(+)-X(2)Sigma(+)
      transition of AlO was applied to ionize the product. The REMPI spectrum was
      analyzed to determine rotational state distributions for v = 0-2 of AlO. For
      several vib-rotational states of AlO, state selected angular and kinetic energy
      distributions were determined by a time-sliced ion imaging technique for the
      first time. Kinetic energy distributions were well represented by that taken into
      account initial energy spreads of collision energy and the population of the spin
      orbit levels of the counter product O((3)P(J)) determined previously. All angular
      distributions showed forward and backward peaks, and the forward peaks were more
      pronounced than the backward one for the states of low internal energy. The
      backward peak intensity became comparable to the forward one for the states of
      high internal energy. These results and the rotational state distributions
      suggested that the reaction proceeds via an intermediate which has a lifetime
      comparable to or shorter than its rotational period.

PMID- 24908006
TI  - Stark and Zeeman effect in the [18.6]3.5 - X(1)4.5 transition of uranium
      monofluoride, UF.
AB  - High resolution spectra of the 0-0 band of the [18.6]3.5 - X(1)4.5 transition of
      uranium monofluoride, UF, obtained using a laser ablation spectrometer, showed a
      perturbation in the upper state. Examination of the Stark and Zeeman effects
      yielded permanent electric dipole moments of 2.01 and 1.88 D and magnetic g
      factors of 3.28 and 3.26 for the ground and excited states, respectively. Both
      the dipole moment and g-factor of the ground state are in good agreement with ab
      initio calculations [I. O. Antonov and M. C. Heaven, J. Phys. Chem. A 117, 9684
      (2013)]. The Zeeman effect results confirm that the ground state arises primarily
      from the U(+)(5f (3)7s(2 4)I(4.5))F(-) configuration and suggest several possible
      configurations for the upper state.

PMID- 24908007
TI  - Intermediate-energy differential and integral cross sections for vibrational
      excitation in alpha-tetrahydrofurfuryl alcohol.
AB  - Differential and integral cross section measurements, for incident electron
      energies in the 20-50 eV range, are reported for excitation of several composite
      vibrational modes in alpha-tetrahydrofurfuryl alcohol (THFA). Optimisation and
      frequency calculations, using GAUSSIAN 09 at the B3LYP/aug-cc-pVDZ level, were
      also undertaken for the two most abundant conformers of THFA, with results being
      reported for their respective mode classifications and excitation energies. Those
      calculations assisted us in the experimental assignments of the composite
      features observed in our measured energy loss spectra. There are, to the best of
      our knowledge, no other experimental or theoretical data currently available in
      the literature against which we can compare the present results. 

PMID- 24908008
TI  - O2(X3Sigmag-) and O2(a1Deltag) charge exchange with simple ions.
AB  - We present theory and experiments which describe charge transfer from the
      X3Sigmag- and a(1)Deltag states of molecular oxygen and atomic and molecular
      cations. Included in this work are new experimental results for O2(a(1)Deltag)
      and the cations O(+), CO(+), Ar(+), and N2+, and new theory based on complete
      active space self-consistent field method calculations and an extended Langevin
      model to calculate rate constants for ground and excited O2 reacting with the
      atomic ions Ar(+), Kr(+), Xe(+), Cl(+), and Br(+). The T-shaped orientation of
      the (X - O2)(+) potential surface is used for the calculations, including all the
      low lying states up to the second singlet state of the oxygen molecule
      b1Sigma(g)+. The calculated rate constants for both O2(X3Sigmag-) and
      O2(a(1)Deltag) show consistent trends with the experimental results, with a
      significant dependence of rate constant on charge transfer exothermicity that
      does not depend strongly on the nature of the cation. The comparisons with theory
      show that partners with exothermicities of about 1 eV have stronger interactions
      with O2, leading to larger Langevin radii, and also that more of the electronic
      states are attractive rather than repulsive, leading to larger rate constants.
      Rate constants for charge transfer involving O2(a(1)Deltag) are similar to those
      for O2(X3Sigmag-) for a given exothermicity ignoring the electronic excitation of
      the O2(a(1)Deltag) state. This means (and the electronic structure calculations
      support) that the ground and excited states of O2 have about the same attractive
      interactions with ions.

PMID- 24908009
TI  - Photolysis of CH3CHO at 248 nm: evidence of triple fragmentation from primary
      quantum yield of CH3 and HCO radicals and H atoms.
AB  - Radical quantum yields have been measured following the 248 nm photolysis of
      acetaldehyde, CH3CHO. HCO radical and H atom yields have been quantified by time
      resolved continuous wave Cavity Ring Down Spectroscopy in the near infrared
      following their conversion to HO2 radicals by reaction with O2. The CH3 radical
      yield has been determined using the same technique following their conversion
      into CH3O2. Absolute yields have been deduced for HCO radicals and H atoms
      through fitting of time resolved HO2 profiles, obtained under various O2
      concentrations, to a complex model, while the CH3 yield has been determined
      relative to the CH3 yield from 248 nm photolysis of CH3I. Time resolved HO2
      profiles under very low O2 concentrations suggest that another unknown HO2
      forming reaction path exists in this reaction system besides the conversion of
      HCO radicals and H atoms by reaction with O2. HO2 profiles can be well reproduced
      under a large range of experimental conditions with the following quantum yields:
      CH3CHO + hnu(248nm) -> CH3CHO*, CH3CHO* -> CH3 + HCO phi(1a) = 0.125 +/- 0.03,
      CH3CHO* -> CH3 + H + CO phi(1e) = 0.205 +/- 0.04, CH3CHO*[Formula: see text]CH3CO
      + HO2 phi(1f) = 0.07 +/- 0.01. The CH3O2 quantum yield has been determined in
      separate experiments as phi(CH3) = 0.33 +/- 0.03 and is in excellent agreement
      with the CH3 yields derived from the HO2 measurements considering that the triple
      fragmentation (R1e) is an important reaction path in the 248 nm photolysis of
      CH3CHO. From arithmetic considerations taking into account the HO2 and CH3
      measurements we deduce a remaining quantum yield for the molecular pathway:
      CH3CHO* -> CH4 + CO phi(1b) = 0.6. All experiments can be consistently explained
      with absence of the formerly considered pathway: CH3CHO* -> CH3CO + H phi(1c) =
      0.

PMID- 24908010
TI  - Analytical Morse/long-range model potential and predicted infrared and microwave
      spectra for a symmetric top-atom dimer: a case study of CH3F-He.
AB  - Four-dimensional ab initio intermolecular potential energy surfaces (PESs) for
      CH3F-He that explicitly incorporates dependence on the Q3 stretching normal mode
      of the CH3F molecule and are parametrically dependent on the other averaged
      intramolecular coordinates have been calculated. Analytical three-dimensional
      PESs for v3(CH3F) = 0 and 1 are obtained by least-squares fitting the
      vibrationally averaged potentials to the Morse/Long-Range potential function
      form. With the 3D PESs, we employ Lanczos algorithm to calculate rovibrational
      levels of the dimer system. Following some re-assignments, the predicted
      transition frequencies are in good agreement with experimental microwave data for
      ortho-CH3F, with the root-mean-square deviation of 0.042 cm(-1). We then provide
      the first prediction of the infrared and microwave spectra for the para-CH3F-He
      dimer. The calculated infrared band origin shifts associated with the nu3
      fundamental of CH3F are 0.039 and 0.069 cm(-1) for para-CH3F-He and ortho-CH3F
      He, respectively. 

PMID- 24908011
TI  - Dynamics of oxygen Rydberg atom generation following O 1s inner-shell excitation
      of H2O.
AB  - The emission of low-energy electrons from H2O has been investigated at photon
      excitation energies in the vicinity of the O 1s ionization threshold. Neutral
      oxygen Rydberg atoms (O*) were found to form, and the correlation between the
      initial inner-shell excited state of H2O and the Rydberg state of O* was
      determined. The initially excited electron in a Rydberg orbital is shown to
      remain associated with O* even after the cleavage of two O-H bonds. We also show
      that the energy discrepancy between two Rydberg states of H2O and O* can be
      explained by the influence of the post-collision interaction, which becomes
      stronger as the excitation energy approaches the 1s ionization threshold. 

PMID- 24908012
TI  - High resolution analysis of three bands of the electronic transition A2Sigma+
      X2Pi of N2O+ radical: 100-000, 000-001, and 001-001.
AB  - In this article three vibrational bands of the electronic transition A(2)Sigma(+)
      X(2)Pi of the N2O(+) radical (100-000, 000-001, and 001-001) are analysed through
      high resolution Fourier transform spectroscopy. The N2O(+) radical was produced
      by Penning ionization of N2O by colliding with metastable atoms of He(2(3)S) in a
      reaction chamber. The spectra was recorded in a spectral range of 24,500-30,000
      cm(-1) and obtained from 200 coadded interferograms recorded at an apodized
      resolution of 0.08 cm(-1). Through a recursive way, the wavenumbers of the
      correspondent rotational transitions were reduced into molecular constants,
      improving the values previously reported. New values for the first vibrational
      energies nu1', nu3", and nu3' are also obtained and compared with previous values
      reported in the literature.

PMID- 24908013
TI  - Dynamical (e,2e) studies of tetrahydropyran and 1,4-dioxane.
AB  - We present experimental and theoretical results for the electron-impact
      ionization of the highest occupied molecular orbitals of tetrahydropyran and 1,4
      dioxane. Using an (e,2e) technique in asymmetric coplanar kinematics, angular
      distributions of the slow ejected electron, with an energy of 20 eV, are measured
      when incident electrons at 250 eV ionize the target and scatter through an angle
      of either -10 degrees  or -15 degrees . The data are compared with calculations
      performed at the molecular 3-body distorted wave level. Fair agreement between
      the theoretical model and the experimental measurements was observed. The similar
      structures for these targets provide key insights for assessing the limitations
      of the theoretical calculations. This study in turn facilitates an improved
      understanding of the dynamics in the ionization process. 

PMID- 24908014
TI  - Model for triplet state engineering in organic light emitting diodes.
AB  - Engineering the position of the lowest triplet state (T1) relative to the first
      excited singlet state (S1) is of great importance in improving the efficiencies
      of organic light emitting diodes and organic photovoltaic cells. We have carried
      out model exact calculations of substituted polyene chains to understand the
      factors that affect the energy gap between S1 and T1. The factors studied are
      backbone dimerisation, different donor-acceptor substitutions, and twisted
      geometry. The largest system studied is an 18 carbon polyene which spans a
      Hilbert space of about 991 * 10(6). We show that for reverse intersystem crossing
      process, the best system involves substituting all carbon sites on one half of
      the polyene with donors and the other half with acceptors. 

PMID- 24908015
TI  - Spectroscopy of Mn atoms isolated in solid 4He.
AB  - We present an experimental study of the laser-induced luminescence spectra of Mn
      atoms in solid helium matrices. We observe transitions of the valence electron
      and of inner-shell electrons. We find that the Mn-He interaction perturbs the
      inner-shell transitions to a lesser extent than the valence-electron transitions.
      The observed lineshapes of the inner-shell transitions of Mn are similar to those
      of an inner-shell transition in Ba studied earlier. At the same time, they are
      more strongly perturbed than the corresponding transitions in Au and Cu under the
      same conditions. We suggest a qualitative explanation of these observations based
      on the atomic bubble model. Our results also suggest that the inner-shell
      transitions of Mn in solid He are more strongly perturbed than the same lines of
      Mn isolated in solid Ar or Kr matrices. 

PMID- 24908016
TI  - Quasiparticle electronic structure and optical absorption of diamond
      nanoparticles from ab initio many-body perturbation theory.
AB  - The excited states of small-diameter diamond nanoparticles in the gas phase are
      studied using the GW method and Bethe-Salpeter equation (BSE) within the ab
      initio many-body perturbation theory. The calculated ionization potentials and
      optical gaps are in agreement with experimental results, with the average error
      about 0.2 eV. The electron affinity is negative and the lowest unoccupied
      molecular orbital is rather delocalized. Precise determination of the electron
      affinity requires one to take the off-diagonal matrix elements of the self-energy
      operator into account in the GW calculation. BSE calculations predict a large
      exciton binding energy which is an order of magnitude larger than that in the
      bulk diamond. 

PMID- 24908017
TI  - Higher-order nonlinearity of refractive index: the case of argon.
AB  - The nonlinear coefficients, n4, of the time-dependent refractive index for argon
      are calculated in the non-resonant optical regime. Second-order polynomial
      fitting of DC-Kerr, gamma((2))(-omega; omega, 0, 0), electric field induced
      second harmonic generation (ESHG), gamma((2))(-2omega; omega, omega, 0), and
      static second-order hyperpolarizability, gamma((2))(0; 0, 0, 0), is performed
      using an auxiliary electric field approach to obtain the corresponding fourth
      order optical properties. A number of basis sets are investigated for the fourth
      order hyperpolarizability processes at 800 nm at coupled cluster singles and
      doubles level of theory, starting with the t-aug-cc-pV5Z basis set and expanding
      that basis set by adding diffuse functions and polarization functions. Comparison
      shows that the results obtained with the t-aug-cc-pV5Z basis are in very good
      agreement with the results obtained using the q-aug-cc-pV5Z, t-aug-cc-pV6Z, and q
      aug-cc-pV6Z basis sets. To calculate the nonlinear refractive index n4, an
      approximate formula is suggested which expresses the related degenerate six-wave
      mixing coefficient, gamma((4))(-omega; omega, -omega, omega, -omega, omega), in
      terms of the DC-Kerr, gamma((4))(-omega; omega, 0, 0, 0, 0), ESHG, gamma((4))(
      2omega; omega, omega, 0, 0, 0), and the static fourth-order hyperpolarizability
      coefficients. The higher-order nonlinear refractive index n4 is found to be
      positive over the wavelengths 300 nm-2000 nm. In the infrared spectral range, the
      obtained values of n4 are in qualitative agreement with the results of Kramers
      Kronig-based calculations. 

PMID- 24908018
TI  - Cavitation in a metallic liquid: homogeneous nucleation and growth of nanovoids.
AB  - Large-scale molecular dynamics (MD) simulations are performed to investigate
      homogeneous nucleation and growth of nanovoids during cavitation in liquid Cu. We
      characterize in detail the atomistic cavitation processes by following the
      temporal evolution of cavities or voids, analyze the nucleation behavior with the
      mean first-passage time (MFPT) and survival probability (SP) methods, and discuss
      the results against classical nucleation theory (CNT), the Tolman equation for
      surface energy, independent calculation of surface tension via integrating the
      stress profiles, the Johnson-Mehl-Avrami (JMA) growth law, and the power law for
      nucleus size distributions. Cavitation in this representative metallic liquid is
      a high energy barrier Poisson processes, and the steady-state nucleation rates
      obtained from statistical runs with the MFPT and SP methods are in agreement. The
      MFPT method also yields the critical nucleus size and the Zeldovich factor.
      Fitting with the Tolman's equation to the MD simulations yields the surface
      energy of a planar interface (~0.9 J m-2) and the Tolman length (0.4-0.5 A), and
      those values are in accord with those from integrating the stress profiles of a
      planar interface. Independent CNT predictions of the nucleation rate (10(33 - 34)
      s(-1) m(-3)) and critical size (3-4 A in radius) are in agreement with the MFPT
      and SP results. The JMA law can reasonably describe the nucleation and growth
      process. The size distribution of subcritical nuclei appears to follow a power
      law with an exponent decreasing with increasing tension owing to coupled
      nucleation and growth, and that of the supercritical nuclei becomes flattened
      during further stress relaxation due to void coalescence.

PMID- 24908019
TI  - An investigation into low-lying electronic states of HCS2 via threshold
      photoelectron imaging.
AB  - Low-energy photoelectron imaging spectra of HCS2(-) are reported for the first
      time. Vibrationally resolved photodetachment transitions from the ground state of
      HCS2(-) to the ground state and low-lying excited states of HCS2 are observed.
      Combined with the ab intio calculations and Franck-Condon simulations, well
      resolved vibrational spectra demonstrate definitive evidence for the resolution
      of the ground-state and excited states of HCS2 radical in the gaseous phase. The
      ground state and two low-lying excited states of HCS2 radical are assigned as
      (2)B2, (2)A2, and (2)A1 states, respectively. The adiabatic electron affinity is
      determined to be 2.910 +/- 0.007 eV. And the term energies of the excited states,
      T0 = 0.451 +/- 0.009 eV and 0.553 +/- 0.009 eV, are directly measured from the
      experimental data, respectively. Angular filtering photoelectron spectra are
      carried out to assist in the spectral band assignment.

PMID- 24908020
TI  - Cationic constraint effects in metaphosphate glasses.
AB  - Temperature-dependent bond constraint theory (BCT) relies on counting the number
      of atomic degrees of freedom for a given topology of a glass network. It has been
      proven useful as a simplistic approach towards the prediction of glass
      properties. However, it breaks down at the inclusion of ionic bonds and is
      therefore presently unable to distinguish the effects of varying cationic species
      with predominantly ionic bonding. Here, we consider the treatment of modifier
      ions in the scope of BCT. Using the example of metaphosphate glasses with a broad
      range of modifier cation species, we find that the theory fails to predict the
      glass properties because of the specific contribution of each modifier species to
      the rigidity of the glass network. We therefore introduce the concept of
      constraint strength, which is a simplistic measure of how strongly the modifiers
      are bound to the surrounding oxygens through columbic forces. 

PMID- 24908021
TI  - Mixtures of protic ionic liquids and molecular cosolvents: a molecular dynamics
      simulation.
AB  - In this work, the effect of molecular cosolvents (water, ethanol, and methanol)
      on the structure of mixtures of these compounds with a protic ionic liquid
      (ethylammonium nitrate) is analyzed by means of classical molecular dynamics
      simulations. Included are as-yet-unreported measurements of the densities of
      these mixtures, used to test our parameterized potential. The evolution of the
      structure of the mixtures throughout the concentration range is reported by means
      of the calculation of coordination numbers and the fraction of hydrogen bonds in
      the system, together with radial and spatial distribution functions for the
      various molecular species and molecular ions in the mixture. The overall picture
      indicates a homogeneous mixing process of added cosolvent molecules, which
      progressively accommodate themselves in the network of hydrogen bonds of the
      protic ionic liquid, contrarily to what has been reported for their aprotic
      counterparts. Moreover, no water clustering similar to that in aprotic mixtures
      is detected in protic aqueous mixtures, but a somehow abrupt replacing of [NO3](
      ) anions in the first hydration shell of the polar heads of the ionic liquid
      cations is registered around 60% water molar concentration. The spatial
      distribution functions of water and alcohols differ in the coordination type,
      since water coordinates with [NO3](-) in a bidentate fashion in the equatorial
      plane of the anion, while alcohols do it in a monodentate fashion, competing for
      the oxygen atoms of the anion. Finally, the collision times of the different
      cosolvent molecules are also reported by calculating their velocity
      autocorrelation functions, and a caging effect is observed for water molecules
      but not in alcohol mixtures. 

PMID- 24908022
TI  - Order and disorder in calcium-silicate-hydrate.
AB  - Despite advances in the characterization and modeling of cement hydrates, the
      atomic order in Calcium-Silicate-Hydrate (C-S-H), the binding phase of cement,
      remains an open question. Indeed, in contrast to the former crystalline model,
      recent molecular models suggest that the nanoscale structure of C-S-H is
      amorphous. To elucidate this issue, we analyzed the structure of a realistic
      simulated model of C-S-H, and compared the latter to crystalline tobermorite, a
      natural analogue of C-S-H, and to an artificial ideal glass. The results clearly
      indicate that C-S-H appears as amorphous, when averaged on all atoms. However, an
      analysis of the order around each atomic species reveals that its structure shows
      an intermediate degree of order, retaining some characteristics of the crystal
      while acquiring an overall glass-like disorder. Thanks to a detailed
      quantification of order and disorder, we show that, while C-S-H retains some
      signatures of a tobermorite-like layered structure, hydrated species are
      completely amorphous. 

PMID- 24908023
TI  - Fast and slow crystal growth kinetics in glass-forming melts.
AB  - Published values of crystal growth rates are compared for supercooled glass
      forming liquids undergoing congruent freezing at a planar crystal-liquid
      interface. For the purposes of comparison pure metals are considered to be glass
      forming systems, using data from molecular-dynamics simulations. For each system,
      the growth rate has a maximum value U(max) at a temperature T(max) that lies
      between the glass-transition temperature T(g) and the melting temperature T(m). A
      classification is suggested, based on the lability (specifically, the propensity
      for fast crystallization), of the liquid. High-lability systems show "fast"
      growth characterized by a high U(max), a low T(max)/T(m), and a very broad peak
      in U vs. T/T(m). In contrast, systems showing "slow" growth have a low U(max), a
      high T(max)/T(m), and a sharp peak in U vs. T/T(m). Despite the difference of
      more than 11 orders of magnitude in U(max) seen in pure metals and in silica, the
      range of glass-forming systems surveyed fit into a common pattern in which the
      lability increases with lower reduced glass-transition temperature (T(g)/T(m))
      and higher fragility of the liquid. A single parameter, a linear combination of
      T(g)/T(m) and fragility, can show a good correlation with U(max). For all the
      systems, growth at U(max) is coupled to the atomic/molecular mobility in the
      liquid. It is found that, across the diversity of glass-forming systems,
      T(max)/T(g) = 1.48 +/- 0.15.

PMID- 24908024
TI  - Liquid-vapor transition and critical behavior of the ultrasoft restricted
      primitive model of polyelectrolytes: a Monte Carlo study.
AB  - We present a Monte Carlo study of the liquid-vapor transition and the critical
      behavior of a model of polyelectrolytes with soft Gaussian charge distributions
      introduced recently by Coslovich, Hansen, and Kahl [J. Chem. Phys. 134, 244514
      (2011)]. A finite size study involving four different volumes in the grand
      canonical ensemble yields a precise determination of the critical temperature,
      chemical potential, and density of the model. Attempts to determine the nature of
      the criticality and to obtain reliable values for the critical exponents are not
      conclusive. 

PMID- 24908025
TI  - Metastable Lennard-Jones fluids. II. Thermal conductivity.
AB  - The method of equilibrium molecular dynamics with the use of the Green-Kubo
      formalism has been used to calculate the thermal conductivity lambda in stable
      and metastable regions of a Lennard-Jones fluid. Calculations have been made in
      the range of reduced temperatures 0.4 <= T* = k(b)T/epsilon <= 2.0 and densities
      0.01 <= rho* = rhosigma3 <= 1.2 on 15 isotherms for 234 states, 130 of which
      refer to metastable regions: superheated and supercooled liquids, supersaturated
      vapor. Equations have been built up which describe the dependence of the regular
      part of the thermal conductivity on temperature and density, and also on
      temperature and pressure. It has been found that in (p, T) variables in the
      region of a liquid-gas phase transition a family of lines of constant value of
      excess thermal conductivity Deltalambda = lambda - lambda0, where lambda0 is the
      thermal conductivity of a dilute gas, has an envelope which coincides with the
      spinodal. Thus, at the approach to the spinodal of a superheated liquid and
      supersaturated vapor (?Deltalambda/?p)T -> infinity, (?Deltalambda/?T)p ->
      infinity.

PMID- 24908026
TI  - The effect of hydrogen bonds on diffusion mechanism of water inside single-walled
      carbon nanotubes.
AB  - Nanopores can serve as a molecule channel for transport of fluid, where water
      diffusion differs remarkably from that of simple particles. Hydrogen bonds play
      an essential role in the diffusion anomaly. Detailed investigations are carried
      out on the systems of rigid (6, 6), (7, 7), (8, 8), (9, 9), and (10, 10) armchair
      carbon nanotubes, solvated with Lennard-Jones water fluids. The role of hydrogen
      bonds is examined by diffusivity statistics and animation snapshots. It is found
      that in small (6,6) CNT, hydrogen bonds tend to aggregate water into a wire and
      lead to rapid collective drift. Confinement can stabilize the hydrogen bond of
      water molecules and enhance its lifetime. In relatively smaller CNTs, the
      diffusion mechanism could be altered by the temperature. Moreover, in larger
      nanotubes hydrogen bonding network allows the water to form regional concentrated
      clusters. This allows water fluid in extremely low density exhibit rather slow
      self-diffusion motion. This fundamental study attempts to provide insights in
      understanding nanoscale delivery system in aqueous solution. 

PMID- 24908027
TI  - Effect of diffusion on Forster resonance energy transfer in low-viscosity
      solution.
AB  - The effect of translational diffusion on Forster resonance energy transfer
      between rhodamine 6G (the donor) and malachite green (the acceptor) was
      investigated by examining the donor's fluorescence decay profile. Eight straight
      chain alkyl alcohols were used, and the temperature of ethanol was changed to
      vary the viscosity; the decay profiles were analyzed using the theory developed
      by Gosele. The critical transfer distance obtained from the decay profile is in
      good agreement with that evaluated using the spectroscopic quantities, and the
      diffusion coefficients are consistent with the Stokes-Einstein relation. The
      fluorescence decay profile was described well by Gosele's theory and the effect
      of diffusion is clearly verified by the temperature/viscosity dependence of the
      diffusion constant. 

PMID- 24908028
TI  - The length and time scales of water's glass transitions.
AB  - Using a general model for the equilibrium dynamics of supercooled liquids, I
      compute from molecular properties the emergent length and time scales that govern
      the nonequilibrium relaxation behavior of amorphous ice prepared by rapid
      cooling. Upon cooling, the liquid water falls out of equilibrium whereby the
      temperature dependence of its relaxation time is predicted to change from super
      Arrhenius to Arrhenius. A consequence of this crossover is that the location of
      the apparent glass transition temperature depends logarithmically on cooling
      rate. Accompanying vitrification is the emergence of a dynamical length-scale,
      the size of which depends on the cooling rate and varies between angstroms and
      tens of nanometers. While this protocol dependence clarifies a number of previous
      experimental observations for amorphous ice, the arguments are general and can be
      extended to other glass forming liquids. 

PMID- 24908029
TI  - Molecular dynamics simulation of electrokinetic flow of an aqueous electrolyte
      solution in nanochannels.
AB  - Electrokinetic flows of an aqueous NaCl solution in nanochannels with negatively
      charged surfaces are studied using molecular dynamics simulations. The four
      transport coefficients that characterize the response to weak electric and
      pressure fields, namely, the coefficients for the electrical current in response
      to the electric field (M(jj)) and the pressure field (M(jm)), and those for the
      mass flow in response to the same fields (M(mj) and M(mm)), are obtained in the
      linear regime using a Green-Kubo approach. Nonequilibrium simulations with
      explicit external fields are also carried out, and the current and mass flows are
      directly obtained. The two methods exhibit good agreement even for large external
      field strengths, and Onsager's reciprocal relation (M(jm) = M(mj)) is numerically
      confirmed in both approaches. The influence of the surface charge density on the
      flow is also considered. The values of the transport coefficients are found to be
      smaller for larger surface charge density, because the counter-ions strongly
      bound near the channel surface interfere with the charge and mass flows. A
      reversal of the streaming current and of the reciprocal electro-osmotic flow,
      with a change of sign of M(mj) due to the excess co-ions, takes places for very
      high surface charge density. 

PMID- 24908030
TI  - Solvation force simulations in atomic force microscopy.
AB  - Solvation force oscillation in octamethylcyclotetrasiloxane (OMCTS) versus the
      distance between an atomic force microscope (AFM) tip and mica substrate has been
      studied through molecular dynamics simulations. A driving spring model in a
      liquid-vapor molecular ensemble is used to explore the force oscillation
      mechanism. It has been found that OMCTS fluid in tip-substrate contact has a
      strong tendency to form a layered structure, starting from n = 8 layers. The
      force profile obtained from simulation is qualitatively similar to those in
      contact mode AFM experiments. However, the bulk-like diffusion and rotation of
      OMCTS molecules underneath the AFM tip suggest that, under the tip-substrate
      confinement geometry, the layered OMCTS film cannot form a solidified structure
      except under n = 2 extreme contact-layer confinement. 

PMID- 24908031
TI  - Inter-cage dynamics in structure I, II, and H fluoromethane hydrates as studied
      by NMR and molecular dynamics simulations.
AB  - Prospective industrial applications of clathrate hydrates as materials for gas
      separation require further knowledge of cavity distortion, cavity selectivity,
      and defects induction by guest-host interactions. The results presented in this
      contribution show that under certain temperature conditions the guest combination
      of CH3F and a large polar molecule induces defects on the clathrate hydrate
      framework that allow intercage guest dynamics. (13)C NMR chemical shifts of a
      CH3F/CH4/TBME sH hydrate and a temperature analysis of the (2)H NMR powder
      lineshapes of a CD3F/THF sII and CD3F/TBME sH hydrate, displayed evidence that
      the populations of CH4 and CH3F in the D and D' cages were in a state of rapid
      exchange. A hydrogen bonding analysis using molecular dynamics simulations on the
      TBME/CH3F and TBME/CH4 sH hydrates showed that the presence of CH3F enhances the
      hydrogen bonding probability of the TBME molecule with the water molecules of the
      cavity. Similar results were obtained for THF/CH3F and THF/CH4 sII hydrates. The
      enhanced hydrogen bond formation leads to the formation of defects in the water
      hydrogen bonding lattice and this can enhance the migration of CH3F molecules
      between adjacent small cages.

PMID- 24908032
TI  - Surface tension and density of Si-Ge melts.
AB  - In this work, the surface tension and density of Si-Ge liquid alloys were
      determined by the pendant drop method. Over the range of measurements, both
      properties show a linear temperature dependence and a nonlinear concentration
      dependence. Indeed, the density decreases with increasing silicon content
      exhibiting positive deviation from ideality, while the surface tension increases
      and deviates negatively with respect to the ideal solution model. Taking into
      account the Si-Ge phase diagram, a simple lens type, the surface tension behavior
      of the Si-Ge liquid alloys was analyzed in the framework of the Quasi-Chemical
      Approximation for the Regular Solutions model. The new experimental results were
      compared with a few data available in the literature, obtained by the
      containerless method. 

PMID- 24908033
TI  - Defects and strain enhancements of second-harmonic generation in Si/Ge
      superlattices.
AB  - Starting from experimental findings and interface growth problems in Si/Ge
      superlattices, we have investigated through ab initio methods the concurrent and
      competitive behavior of strain and defects in the second-harmonic generation
      process. Interpreting the second-harmonic intensities as a function of the
      different nature and percentage of defects together with the strain induced at
      the interface between Si and Ge, we found a way to tune and enhance the second
      harmonic generation response of these systems. 

PMID- 24908034
TI  - Configuration change of NO on Cu(110) as a function of temperature.
AB  - The bonding structure of nitric oxide (NO) on Cu(110) is studied by means of
      scanning tunneling microscopy, reflection absorption infrared spectroscopy, and
      electron energy loss spectroscopy at 6-160 K. At low temperatures, the NO
      molecule adsorbs at the short bridge site via the N end in an upright
      configuration. At around 50 K, this turns into a flat configuration, in which
      both the N and O atoms interact with the surface. The flat configuration is
      characterized by the low-frequency N-O stretching mode at 855 cm(-1). The flat
      lying NO flips back and forth when the temperature increases to ~80 K, and
      eventually dissociates at ~160 K. We propose a potential energy diagram for the
      conversion of NO on the surface.

PMID- 24908036
TI  - Conformations, transverse fluctuations, and crossover dynamics of a semi-flexible
      chain in two dimensions.
AB  - We present a unified scaling description for the dynamics of monomers of a
      semiflexible chain under good solvent condition in the free draining limit. We
      consider both the cases where the contour length L is comparable to the
      persistence length l(p) and the case L ? l(p). Our theory captures the early time
      monomer dynamics of a stiff chain characterized by t(3/4) dependence for the mean
      square displacement of the monomers, but predicts a first crossover to the Rouse
      regime of t(2nu/1 + 2nu) for tau1 ~ l(p)3, and a second crossover to the purely
      diffusive dynamics for the entire chain at tau2 ~ L(5/2). We confirm the
      predictions of this scaling description by studying monomer dynamics of dilute
      solution of semi-flexible chains under good solvent conditions obtained from our
      Brownian dynamics (BD) simulation studies for a large choice of chain lengths
      with number of monomers per chain N = 16-2048 and persistence length l(p) = 1-500
      Lennard-Jones units. These BD simulation results further confirm the absence of
      Gaussian regime for a two-dimensional (2D) swollen chain from the slope of the
      plot of ?R(N)2?/2Ll(p) ~ L/l(p) which around L/l(p) ~ 1 changes suddenly from
      (L/l(p)) -> (L/l(p))(0.5), also manifested in the power law decay for the bond
      autocorrelation function disproving the validity of the worm-like-chain in 2D. We
      further observe that the normalized transverse fluctuations of the semiflexible
      chains for different stiffness ?(?l(?)2?)/L as a function of renormalized contour
      length L/l(p) collapse on the same master plot and exhibits power law scaling
      ?(?l(?)2?)/L ~ (L/l(p))(n) at extreme limits, where eta = 0.5 for extremely stiff
      chains (L/l(p) ? 1), and eta = -0.25 for fully flexible chains. Finally, we
      compare the radial distribution functions obtained from our simulation studies
      with those obtained analytically.

PMID- 24908037
TI  - Accurate prediction of the linear viscoelastic properties of highly entangled
      mono and bidisperse polymer melts.
AB  - We present a hierarchical computational methodology which permits the accurate
      prediction of the linear viscoelastic properties of entangled polymer melts
      directly from the chemical structure, chemical composition, and molecular
      architecture of the constituent chains. The method entails three steps: execution
      of long molecular dynamics simulations with moderately entangled polymer melts,
      self-consistent mapping of the accumulated trajectories onto a tube model and
      parameterization or fine-tuning of the model on the basis of detailed simulation
      data, and use of the modified tube model to predict the linear viscoelastic
      properties of significantly higher molecular weight (MW) melts of the same
      polymer. Predictions are reported for the zero-shear-rate viscosity eta0 and the
      spectra of storage G'(omega) and loss G"(omega) moduli for several mono and
      bidisperse cis- and trans-1,4 polybutadiene melts as well as for their MW
      dependence, and are found to be in remarkable agreement with experimentally
      measured rheological data.

PMID- 24908035
TI  - Mixed confinement regimes during equilibrium confinement spectroscopy of DNA.
AB  - We have used a combination of fluorescence microscopy experiments and Pruned
      Enriched Rosenbluth Method simulations of a discrete wormlike chain model to
      measure the mean extension and the variance in the mean extension of lambda-DNA
      in 100 nm deep nanochannels with widths ranging from 100 nm to 1000 nm in
      discrete 100 nm steps. The mean extension is only weakly affected by the channel
      aspect ratio. In contrast, the fluctuations of the chain extension qualitatively
      differ between rectangular channels and square channels with the same cross
      sectional area, owing to the "mixing" of different confinement regimes in the
      rectangular channels. The agreement between experiment and simulation is very
      good, using the extension due to intercalation as the only adjustable parameter. 

PMID- 24908038
TI  - Role of filament annealing in the kinetics and thermodynamics of nucleated
      polymerization.
AB  - The formation of nanoscale protein filaments from soluble precursor molecules
      through nucleated polymerization is a common form of supra-molecular assembly
      phenomenon. This process underlies the generation of a range of both functional
      and pathological structures in nature. Filament breakage has emerged as a key
      process controlling the kinetics of the growth reaction since it increases the
      number of filament ends in the system that can act as growth sites. In order to
      ensure microscopic reversibility, however, the inverse process of fragmentation,
      end-to-end annealing of filaments, is a necessary component of a consistent
      description of such systems. Here, we combine Smoluchowski kinetics with
      nucleated polymerization models to generate a master equation description of
      protein fibrillization, where filamentous structures can undergo end-to-end
      association, in addition to elongation, fragmentation, and nucleation processes.
      We obtain self-consistent closed-form expressions for the growth kinetics and
      discuss the key physics that emerges from considering filament fusion relative to
      current fragmentation only models. Furthermore, we study the key time scales that
      describe relaxation to equilibrium. 

PMID- 24908039
TI  - Formation of liquid crystalline phases in aqueous suspensions of platelet-like
      tripalmitin nanoparticles.
AB  - Suspensions of platelet-like shaped tripalmitin nanocrystals stabilized by the
      pure lecithin DLPC and the lecithin blend S100, respectively, have been studied
      by small-angle x-ray scattering (SAXS) and optical observation of their
      birefringence at different tripalmitin (PPP) concentrations phi(PPP). It could be
      demonstrated that the platelets of these potential drug delivery systems start to
      form a liquid crystalline phase already at pharmaceutically relevant
      concentrations phi(PPP) of less than 10 wt. %. The details of this liquid
      crystalline phase are described here for the first time. As in a previous study
      [A. Illing et al., Pharm. Res. 21, 592 (2004)] some platelets are found to self
      assemble into lamellar stacks above a critical tripalmitin concentration
      phi(PPP)(st) of 4 wt. %. In this study another critical concentration
      phi(PPP)(lc) ~ 7 wt. % for DLPC and phi(PPP)(lc) ~ 9 wt. % for S100 stabilized
      dispersions, respectively, has been observed. phi(PPP)(lc) describes the
      transition from a phase of randomly oriented stacked lamellae and remaining non
      assembled individual platelets to a phase in which the stacks and non-assembled
      platelets exhibit an overall preferred orientation. A careful analysis of the
      experimental data indicates that for concentrations above phi(PPP)(lc) the
      stacked lamellae start to coalesce to rather small liquid crystalline domains of
      nematically ordered stacks. These liquid crystalline domains can be individually
      very differently oriented but possess an overall preferred orientation over
      macroscopic length scales which becomes successively more expressed when further
      increasing phi(PPP). The lower critical concentration for the formation of liquid
      crystalline domains of the DLPC-stabilized suspension compared to phi(PPP)(lc) of
      the S100-stabilized suspension can be explained by a larger aspect ratio of the
      corresponding tripalmitin platelets. A geometrical model based on the excluded
      volumes of individual platelets and stacked lamellae has been developed and
      successfully applied to reproduce the critical volume fractions for both, the
      onset of stack formation and the appearance of the liquid crystalline phase.

PMID- 24908040
TI  - Stochastic interactions of two Brownian hard spheres in the presence of
      depletants.
AB  - A quantitative analysis is presented for the stochastic interactions of a pair of
      Brownian hard spheres in non-adsorbing polymer solutions. The hard spheres are
      hypothetically trapped by optical tweezers and allowed for random motion near the
      trapped positions. The investigation focuses on the long-time correlated Brownian
      motion. The mobility tensor altered by the polymer depletion effect is computed
      by the boundary integral method, and the corresponding random displacement is
      determined by the fluctuation-dissipation theorem. From our computations it
      follows that the presence of depletion layers around the hard spheres has a
      significant effect on the hydrodynamic interactions and particle dynamics as
      compared to pure solvent and uniform polymer solution cases. The probability
      distribution functions of random walks of the two interacting hard spheres that
      are trapped clearly shift due to the polymer depletion effect. The results show
      that the reduction of the viscosity in the depletion layers around the spheres
      and the entropic force due to the overlapping of depletion zones have a
      significant influence on the correlated Brownian interactions. 

PMID- 24908041
TI  - The kinetics of mutarotation in L-fucose as monitored by dielectric and infrared
      spectroscopy.
AB  - Fourier Transform Infrared Spectroscopy and Broadband Dielectric Spectroscopy are
      combined to trace kinetics of mutarotation in L-fucose. After quenching molten
      samples down to temperatures between T = 313 K and 328 K, the concentrations of
      two anomeric species change according to a simple exponential time dependence, as
      seen by an increase in absorbance of specific IR-vibrations. In contrast, the
      dielectric spectra reveal a slowing down of the structural (alpha-) relaxation
      process according to a stretched exponential time dependence (stretching exponent
      of 1.5 +/- 0.2). The rates of change in the IR absorption for alpha- and beta
      fucopyranose are (at T = 313 K) nearly one decade faster than that of the
      intermolecular interactions as measured by the shift of the alpha-relaxation.
      This reflects the fact that the alpha-relaxation monitors the equilibration at a
      mesoscopic length scale, resulting from fluctuations in the anomeric composition.

PMID- 24908043
TI  - Unusual mechanism of post-operative pacemaker lead dislodgement.

PMID- 24908042
TI  - Iatrogenic extra-pleural haematoma following cardiac device implantation.

PMID- 24908044
TI  - Long-standing arterial hypertension is associated with Pitx2 down-regulation in a
      rat model of spontaneous atrial tachyarrhythmias.
AB  - AIMS: The timecourse of left atrial Pitx2 down-regulation in the setting of
      atrial tachyarrhythmias remains unknown. Accordingly, we aimed to assess the age
      dependency of left atrial Pitx2 expression in an experimental model of
      spontaneous atrial tachyarrhythmias in rats. METHODS AND RESULTS: Atrial sampling
      was performed in three groups (n = 4 each) of young (14-week-old), adult (24-week
      old), and ageing (48-week-old) spontaneously hypertensive rats (SHRs), in which
      we previously demonstrated the age dependency of spontaneous atrial
      tachyarrhythmias, and three groups (n = 4 each) of age-matched normotensive
      Wistar-Kyoto (WKY) rats. mRNA expression of Pitx2 was studied using real-time
      polymerase chain reaction. Ageing SHRs presented significantly lower left atrial
      Pitx2 expressions compared with age-matched WKY rats (P = 0.02), while no
      significant difference was observed between young or adult SHRs and age-matched
      WKY rats (both P > 0.05). Among SHRs, Pitx2 expressions showed a progressive, age
      dependent decrease (34.9 +/- 6.7 in young SHRs, 17.1 +/- 3.6 in adult SHRs, and
      10.7 +/- 1.7 in ageing SHRs, P = 0.04) and were significantly negatively
      correlated with both age (Spearman r = -0.86, P < 0.01) and heart weight
      (Spearman r = -0.76, P < 0.01). CONCLUSION: The present study suggests the
      presence of age-dependent left atrial Pitx2 down-regulation in SHRs. The strong
      negative correlation between left atrial Pitx2 expression and heart weight among
      SHRs may indicate a link between long-standing arterial hypertension and Pitx2
      related atrial arrhythmogenicity.

PMID- 24908045
TI  - Characterization of extended-spectrum beta-lactamase (ESBL)-producing Escherichia
      coli obtained from Danish pigs, pig farmers and their families from farms with
      high or no consumption of third- or fourth-generation cephalosporins.
AB  - OBJECTIVES: To compare and characterize extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli from pigsties, pig farmers and their families on farms
      with previous high or no use of third- or fourth-generation cephalosporins.
      METHODS: Twenty farms with no third- or fourth-generation cephalosporin use and
      19 herds with previous frequent use were included. The ESBL-producing isolates
      detected in humans and pigs were characterized by ESBL genotype, PFGE,
      susceptibility to non-beta-lactam antibiotics and phylotype, and selected
      isolates were characterized by multilocus sequence typing (MLST). Furthermore,
      transferability of bla(CTX-M-)1 from both human and pig isolates was studied and
      plasmid incompatibility groups were defined. The volunteers answered a
      questionnaire including epidemiological risk factors for carriage of ESBL
      producing E. coli. RESULTS: ESBL-producing E. coli was detected in pigs on 79% of
      the farms with high consumption of cephalosporins compared with 20% of the pigs
      on farms with no consumption. ESBL-producing E. coli was detected in 19 of the
      195 human participants and all but one had contact with pigs. The genes found in
      both humans and pigs at the same farms were blaCTX-M-1 (eight farms), bla(CTX-M
      14) (one farm) and bla(SHV-12) (one farm). At four farms ESBL-producing E. coli
      isolates with the same CTX-M enzyme, phylotype, PFGE type and MLST type were
      detected in both pigs and farmers. The majority of the plasmids with bla(CTX-M-1)
      were transferable by conjugation and belonged to incompatibility group IncI1,
      IncF, or IncN. CONCLUSIONS: The present study shows an increased frequency of
      ESBL-producing E. coli on farms with high consumption of third- or fourth
      generation cephalosporins and indicates transfer of either ESBL-producing E. coli
      or plasmids between pigs and farmers.

PMID- 24908046
TI  - Presence of disinfectant resistance genes in Escherichia coli isolated from
      retail meats in the USA.
AB  - OBJECTIVES: To examine the distribution of all genes known to be responsible for
      resistance to quaternary ammonium compounds (QACs), and their association with
      resistance to QACs and other antimicrobials, in Escherichia coli recovered from
      retail meats. METHODS: A total of 570 strains of E. coli isolated from US retail
      meats in 2006 were screened for the presence of 10 QAC resistance genes [qacE,
      qacEDelta1, qacF, qacG, emrE, sugE(c), sugE(p), mdfA and ydgE/ydgF]. The MICs of
      six common disinfectants were determined using an agar dilution method. Possible
      associations between the presence of the gene and bacterial resistance to QACs
      and antimicrobials were investigated. RESULTS: emrE, sugE(c), mdfA and ydgE/ydgF
      were commonly present (77.2%-100%) in the E. coli isolates, but qac and sugE(p)
      were less prevalent (0.4%-22.3%). emrE-mdfA-sugE(c)-ydgE/F was the most common
      QAC resistance gene profile. A significant association was found between
      antimicrobial resistance and the presence of sugE(p) and qacEDelta1 (P < 0.05).
      Antimicrobial-resistant E. coli isolates tended to contain more diverse
      combinations of disinfectant resistance genes than susceptible ones. All isolates
      showed reduced susceptibility to five of six disinfectants compared with the
      control strains. Higher MICs were generally associated with the presence of qac
      and sugE(p) genes. CONCLUSIONS: The QAC resistance genes were commonly present
      among E. coli isolated from retail meats, and the qac and sugE(p) genes were
      highly associated with multidrug resistance phenotypes. Using QACs in the food
      industry may not be as effective as expected and could provide selection pressure
      for strains with acquired resistance to other antimicrobials.

PMID- 24908048
TI  - Human ability in identification of location and pulse number for electrocutaneous
      stimulation applied on the forearm.
AB  - BACKGROUND: The need of a sensory feedback system that would improve users'
      acceptance in prostheses is generally recognized. Feedback of hand opening and
      position are among the most important concerns of prosthetic users. To address
      the two concerns, this study investigated the human capability to identify pulse
      number and location when electrical stimulation applied on the forearm skin. The
      pulse number may potentially be used to encode the opening of prosthetic hands
      and stimulation location to encode finger position. METHODS: Ten able-bodied
      subjects participated in the study. Three electrodes were placed transversely
      across the ventral forearm spatially encoding three fingers (i.e., thumb, index,
      and middle finger). Five different pulse numbers (1, 4, 8, 12, and 20) encoded
      five levels of hand opening. The study consisted of three experiments. In the
      three experiments, each after a training session, the subjects were required to
      identify among: (a) five stimulation locations, (b) five pulse numbers, or (c)
      ten paired combinations of location and pulse number, respectively. The subjects'
      performance in the three identification tasks was evaluated. RESULTS: The main
      results included: 1) the overall identification rate for stimulation location was
      92.2 +/- 6.2%, while the success rate in two-site stimulation was lower than one
      site stimulation; 2) the overall identification rate for pulse number was 90.8 +/
      6.0%, and the subjects showed different performance in identification of the
      five pulse numbers; 3) the overall identification rate decreased to 80.2 +/-
      11.7% when the subjects were identifying paired parameters. CONCLUSIONS: The
      results indicated that the spatial (location) and temporal (pulse number)
      identification performance are promising in electrocutaneous stimulation on the
      forearm. The performance degraded when both parameters had to be identified
      likely due to increased cognitive load resulting from multiple tasks. Utilizing
      the proposed coding strategy in practical prosthetic hands remains to be
      investigated for clinical evaluation of its feasibility.

PMID- 24908047
TI  - The M-T hook structure increases the potency of HIV-1 fusion inhibitor
      sifuvirtide and overcomes drug resistance.
AB  - OBJECTIVES: Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1
      gp41 are potent fusion inhibitors. We have recently demonstrated that the unique
      M-T hook structure preceding the pocket-binding motif of CHR peptide-based
      inhibitors can greatly improve their antiviral activity. In this study, we
      applied the M-T hook structure to optimize sifuvirtide (SFT), a potent CHR
      derived inhibitor currently under Phase III clinical trials in China. METHODS:
      The peptide MT-SFT was generated by incorporating two M-T hook residues (Met-Thr)
      into the N-terminus of sifuvirtide. Multiple structural and functional approaches
      were used to determine the biophysical properties and antiviral activity of MT
      SFT. RESULTS: The high-resolution crystal structure of MT-SFT reveals a highly
      conserved M-T hook conformation. Compared with sifuvirtide, MT-SFT exhibited a
      significant improvement in the ability to bind to the N-terminal heptad repeat,
      to block the formation of the six helix bundle and to inhibit HIV-1 Env-mediated
      cell fusion, viral entry and infection. Importantly, MT-SFT was fully active
      against sifuvirtide- and enfuvirtide (T20)-resistant HIV-1 variants and displayed
      a high genetic barrier to developing drug resistance. CONCLUSIONS: Our studies
      have verified that the M-T hook structure offers a general strategy for designing
      novel HIV-1 fusion inhibitors and provide new insights into viral entry and
      inhibition.

PMID- 24908049
TI  - Adherence to and effectiveness of an individually tailored home-based exercise
      program for frail older adults, driven by mobility monitoring: design of a
      prospective cohort study.
AB  - BACKGROUND: With the number of older adults in society rising, frailty becomes an
      increasingly prevalent health condition. Regular physical activity can prevent
      functional decline and reduce frailty symptoms. In particular, home-based
      exercise programs can be beneficial in reducing frailty of older adults and fall
      risk, and in improving associated physiological parameters. However, adherence to
      home-based exercise programs is generally low among older adults. Current
      developments in technology can assist in enlarging adherence to home-based
      exercise programs. This paper presents the rationale and design of a study
      evaluating the adherence to and effectiveness of an individually tailored, home
      based physical activity program for frail older adults driven by mobility
      monitoring through a necklace-worn physical activity sensor and remote feedback
      using a tablet PC. METHODS/DESIGN: Fifty transitionally frail community-dwelling
      older adults will join a 6-month home-based physical activity program in which
      exercises are provided in the form of exercise videos on a tablet PC and daily
      activity is monitored by means of a necklace-worn motion sensor. Participants
      exercise 5 times a week. Exercises are built up in levels and are individually
      tailored in consultation with a coach through weekly telephone contact.
      DISCUSSION: The physical activity program driven by mobility monitoring through a
      necklace-worn sensor and remote feedback using a tablet PC is an innovative
      method for physical activity stimulation in frail older adults. We hypothesize
      that, if participants are sufficiently adherent, the program will result in
      higher daily physical activity and higher strength and balance assessed by
      physical tests compared to baseline. If adherence to and effectiveness of the
      program is considered sufficient, the next step would be to evaluate the
      effectiveness with a randomised controlled trial. The knowledge gained in this
      study can be used to develop and fine-tune the application of innovative
      technology in home-based exercise programs. TRIAL REGISTRATION: Nederlands Trial
      Register (NTR); trial number 4265. The study was prospectively registered
      (registration date 14/11/2013).

PMID- 24908051
TI  - Improvements of tolerance to stress conditions by genetic engineering in
      Saccharomyces cerevisiae during ethanol production.
AB  - Saccharomyces cerevisiae, industrial yeast isolate, has been of great interest in
      recent years for fuel ethanol production. The ethanol yield and productivity
      depend on many inhibitory factors during the fermentation process such as
      temperature, ethanol, compounds released as the result of pretreatment
      procedures, and osmotic stress. An ideal strain should be able to grow under
      different stress conditions occurred at different fermentation steps. Development
      of tolerant yeast strains can be achieved by reprogramming pathways supporting
      the ethanol metabolism by regulating the energy balance and detoxicification
      processes. Complex gene interactions should be solved for an in-depth
      comprehension of the yeast stress tolerance mechanism. Genetic engineering as a
      powerful biotechnological tool is required to design new strategies for
      increasing the ethanol fermentation performance. Upregulation of stress tolerance
      genes by recombinant DNA technology can be a useful approach to overcome
      inhibitory situations. This review presents the application of several genetic
      engineering strategies to increase ethanol yield under different stress
      conditions including inhibitor tolerance, ethanol tolerance, thermotolerance, and
      osmotolerance. 

PMID- 24908052
TI  - Ball milling pretreatment of oil palm biomass for enhancing enzymatic hydrolysis.
AB  - Oil palm biomass, namely empty fruit bunch and frond fiber, were pretreated using
      a planetary ball mill. Particle sizes and crystallinity index values of the oil
      palm biomass were significantly reduced with extended ball mill processing time.
      The treatment efficiency was evaluated by the generation of glucose, xylose, and
      total sugar conversion yields from the pretreatment process compared to the
      amount of sugars from raw materials. Glucose and xylose contents were determined
      using high-performance liquid chromatography. An increasing trend in glucose and
      xylose yield as well as total sugar conversion yield was observed with decreasing
      particle size and crystallinity index. Oil palm frond fiber exhibited the best
      material yields using ball milling pretreatment with generated glucose, xylose,
      and total sugar conversion yields of 87.0, 81.6, and 85.4%, respectively. In
      contrast, oil palm empty fruit bunch afforded glucose and xylose of 70.0 and
      82.3%, respectively. The results obtained in this study showed that ball mill
      treated oil palm biomass is a suitable pretreatment method for high conversion of
      glucose and xylose.

PMID- 24908050
TI  - The crystal structure of pyrimidine/thiamin biosynthesis precursor-like domain
      containing protein CAE31940 from proteobacterium Bordetella bronchiseptica RB50,
      and evolutionary insight into the NMT1/THI5 family.
AB  - We report a 2.0 A structure of the CAE31940 protein, a proteobacterial NMT1/THI5
      like domain-containing protein. We also discuss the primary and tertiary
      structure similarity with its homologs. The highly conserved FGGXMP motif was
      identified in CAE31940, which corresponds to the GCCCX motif located in the
      vicinity of the active center characteristic for THi5-like proteins found in
      yeast. This suggests that the FGGXMP motif may be a unique hallmark of
      proteobacterial NMT1/THI5-like proteins. 

PMID- 24908053
TI  - Bottom-up and top-down processes interact to modify intraguild interactions in
      resource-pulse environments.
AB  - Top predators are declining globally, in turn allowing populations of smaller
      predators, or mesopredators, to increase and potentially have negative effects on
      biodiversity. However, detection of interactions among sympatric predators can be
      complicated by fluctuations in the background availability of resources in the
      environment, which may modify both the numbers of predators and the strengths of
      their interactions. Here, we first present a conceptual framework that predicts
      how top-down and bottom-up interactions may regulate sympatric predator
      populations in environments that experience resource pulses. We then test it
      using 2 years of remote-camera trapping data to uncover spatial and temporal
      interactions between a top predator, the dingo Canis dingo, and the mesopredatory
      European red fox Vulpes vulpes and feral cat Felis catus, during population
      booms, declines and busts in numbers of their prey in a model desert system. We
      found that dingoes predictably suppress abundances of the mesopredators and that
      the effects are strongest during declines and busts in prey numbers. Given that
      resource pulses are usually driven by large yet infrequent rains, we conclude
      that top predators like the dingo provide net benefits to prey populations by
      suppressing mesopredators during prolonged bust periods when prey populations are
      low and potentially vulnerable.

PMID- 24908054
TI  - Clinical research of holmium laser therapy in extramammary Paget's disease.
AB  - This study aims to investigate the safety and efficiency of the holmium laser
      therapy in extramammary Paget's disease. The clinical data of 61 patients was
      collected since 2002 to 2012, confirmed as non-subcutaneous invasive extramammary
      Paget's disease by biopsy and underwent surgery. All patients were divided into
      two groups. Group A included 30 patients who underwent the holmium laser therapy.
      Group B included 31 patients who underwent the traditional surgical therapy. The
      clinical data of all patients included preoperative, intraoperative, and
      postoperative management and follow-up records. Compared with the traditional
      operation group, the holmium laser group had a shorter operation time and was
      easier to perform. There were no significant differences between the two groups
      in cases of intraoperative and postoperative complications, the recurrence-free
      survival, and the disease-specific survival. But the holmium laser group had a
      longer recovery time than the traditional operation group in large and deep
      nidus. Multiple-factor analysis of prognostic parameters of 61 patients confirmed
      that any of these two methods chosen was not a prognostic parameter for
      recurrence-free survival. The holmium laser therapy might prove to be a
      preferable alternative to the traditional operative therapy of extramammary
      Paget's disease. However, the holmium laser therapy did not demonstrate to have
      an obvious advantage over traditional operative therapy in the recurrence-free
      survival and the disease-specific survival. 

PMID- 24908055
TI  - The European Cystic Fibrosis Society Patient Registry: valuable lessons learned
      on how to sustain a disease registry.
AB  - BACKGROUND: Disease registries have the invaluable potential to provide an
      insight into the natural history of the disease under investigation, to provide
      useful information (e.g. through health indicators) for planning health care
      services and to identify suitable groups of patients for clinical trials
      enrolment. However, the establishment and maintenance of disease registries is a
      burdensome initiative from economical and organisational points of view and
      experience sharing on registries management is important to avoid waste of
      resources. The aim of this paper is to discuss the problems embedded in the
      institution and management of an international disease registry to warn against
      common mistakes that can derail the best of intentions: we share the experience
      of the European Cystic Fibrosis Society Patient Registry, which collects data on
      almost 30,000 patients from 23 countries. METHODS: We discuss the major problems
      that researchers often encounter in the creation and management of disease
      registries: definition of the aims the registry has to reach, definition of the
      criteria for patients referral to the registry, definition of the information to
      record, set up of a data quality process, handling of missing data, maintenance
      of data confidentiality, regulation of data use and dissemination of research
      results. RESULTS: We give examples on how many crucial aspects were solved by the
      European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion
      criteria and variables definition, data management, data quality controls,
      missing data handling, confidentiality maintenance, data use and results
      dissemination. CONCLUSIONS: We suggest an extensive literature research and
      discussions in working groups with different stake holders, including patient
      representatives, on the objectives, inclusion criteria and the information to
      record. We propose to pilot the recording of few variables and test the
      applicability of their definition first. The use of a shared electronic platform
      for data collection that automatically computes derived variables, and
      automatically performs basic data quality controls is a good data management
      practice, that also helps in reducing missing data. We found crucial for success
      the collaboration with existing national and international registries, cystic
      fibrosis organisations and patients' associations.

PMID- 24908056
TI  - Successful catheter ablation for retrograde limb of inter-fascicular reentrant
      ventricular tachycardia in a case with an electrical storm.

PMID- 24908058
TI  - Utility of superior mesenteric artery Doppler and maternal pancreatic size for
      predicting gestational diabetes mellitus.
AB  - AIM: The aim of this study was to assess the relationship between the maternal
      superior mesenteric artery Doppler, pancreatic size and gestational diabetes
      mellitus (GDM). METHODS: Two hundred and fifty-eight consecutive, pregnant women
      between 20 and 22 weeks of gestation underwent routine fetal anomaly screening.
      All subjects underwent maternal superior mesenteric artery Doppler and pancreatic
      size measurement of head, corpus and tail during screening. Screening was done
      with 50 g glucose challenge test (GCT) at gestational age 24-28 weeks. The
      patients who were having an abnormal GCT were subjected to 100 g GCT. Subjects
      were divided into two groups such as pregnancies with gestational diabetes and
      normal pregnancies. Relationship between Doppler and pancreatic measurements with
      GDM was analyzed. RESULTS: Out of 258 screened pregnancies, 28 (10.9 %) were
      diagnosed as GDM. There were significant differences between GDM positive and
      negative cases in terms of pancreatic body size (17.5 vs. 14.4 mm, p = 0.05),
      superior mesenteric artery Doppler systolic/diastolic ratio (S/D) (4.2 vs. 3.4)
      and resistance index (RI) (0.72 vs. 0.68) values. Superior mesenteric artery
      Doppler S/D (AUC = 0.761, p < 0.001) and RI (AUC = 0.762, p < 0.001) indices were
      significant predictors for GDM. CONCLUSION: Superior mesenteric artery Doppler
      and pancreatic size evaluation may be utilized to detect abnormal glucose
      metabolism during pregnancy care.

PMID- 24908057
TI  - Factors associated with quality of life measured by EQ-5D in patients with
      nontuberculous mycobacterial pulmonary disease.
AB  - PURPOSE: The impact of pulmonary nontuberculous mycobacterial (pNTM) disease on
      health-related quality of life (HRQoL) has not received significant attention in
      the literature. In this study, we compared the HRQoL in patients with pNTM
      disease and healthy subjects and identified influencing factors using EuroQol 5D
      (EQ-5D) data. METHODS: The present study used an age- and sex-matched case
      control analysis from a cohort of 85 pNTM patients and 340 participants from a
      national survey. Baseline EQ-5D utility scores and EQ-5D visual analog scale
      (VAS) scores were measured in both groups. In patients with pNTM disease, the
      factors affecting EQ-5D were identified using multiple linear regression
      analysis. RESULTS: While the median EQ-5D VAS scores were lower in pNTM patients
      than in the control subjects (pNTM, 70; control, 80; P < 0.001), the median EQ-5D
      utility scores were similar in two groups (both, 1.000, P = 0.878).
      Interestingly, the percentage of subjects reporting problems on the
      anxiety/depression dimension was higher for patients with pNTM disease (18.8 %)
      compared with the control subjects (11.5 %, P = 0.07). In multivariate analysis,
      increasing severity of forced expired volume in one second (FEV1) decline was
      associated with a significant decrease in EQ-5D scores of pNTM patients.
      CONCLUSIONS: This study suggested the EQ-5D may not be useful instrument in pNTM
      patients due to ceiling effect of EQ-5D and mild disease activity. Patients with
      pNTM disease tended to report more reduced health status and more problems with
      anxiety/depression than the healthy controls. Lung function, measured by FEV1,
      was independently associated with EQ-5D scores in patients with pNTM disease.

PMID- 24908059
TI  - Discovery of a new antiviral protein isolated Lonomia obliqua analysed by
      bioinformatics and real-time approaches.
AB  - This study presents a new recombinant protein that acts as a powerful antiviral
      (rAVLO-recombinant Antiviral protein of Lonomia obliqua). It was able to reduce
      the replication by 10(6) fold for herpes virus and by 10(4) fold for rubella
      virus. RT-PCR of viral RNA rAVLO treated infected cells also showed similar rate
      of inhibition in replication. The analysis of this protein by bioinformatics
      suggests that this protein is globular, secreted with a signal peptide and has
      the ability to bind to MHC class I. It was found that there are several protein
      binding sites with various HLA and a prevalence of alpha-helices in the N
      terminal region (overall classified as a alpha/beta protein type). BLAST
      similarity sequence search for corresponding cDNA did not reveal a similar
      sequence in Genbank, suggesting that it is from a novel protein family. In this
      study we have observed that this recombinant protein and hemolymph has a potent
      antiviral action. This protein was produced in a baculovirus/Sf-9 system.
      Therefore, these analyses suggest that this novel polypeptide is a candidate as a
      broad spectrum antiviral. 

PMID- 24908060
TI  - Marine-derived Penicillium in Korea: diversity, enzyme activity, and antifungal
      properties.
AB  - The diversity of marine-derived Penicillium from Korea was investigated using
      morphological and multigene phylogenetic approaches, analyzing sequences of the
      internal transcribed spacer region, beta-tubulin gene, and RNA polymerase subunit
      II gene. In addition, the biological activity of all isolated strains was
      evaluated. We tested for the extracellular enzyme activity of alginase,
      endoglucanase, and beta-glucosidase, and antifungal activity against two plant
      pathogens (Colletotrichum acutatum and Fusarium oxysporum). A total of 184
      strains of 36 Penicillium species were isolated, with 27 species being
      identified. The most common species were Penicillium polonicum (19.6 %), P.
      rubens (11.4 %), P. chrysogenum (11.4 %), and P. crustosum (10.9 %). The
      diversity of Penicillium strains isolated from soil (foreshore soil and sand) and
      marine macroorganisms was higher than the diversity of strains isolated from
      seawater. While many of the isolated strains showed alginase and beta-glucosidase
      activity, no endoglucanase activity was found. More than half the strains (50.5
      %) showed antifungal activity against at least one of the plant pathogens tested.
      Compared with other strains in this study, P. citrinum (strain SFC20140101-M662)
      showed high antifungal activity against both plant pathogens. The results
      reported here expand our knowledge of marine-derived Penicillium diversity. The
      relatively high proportion of strains that showed antifungal and enzyme activity
      demonstrates that marine-derived Penicillium have great potential to be used in
      the production of natural bioactive products for pharmaceutical and/or industrial
      use. 

PMID- 24908061
TI  - A single nucleotide polymorphism in PIK3CA gene is inversely associated with P53
      protein expression in breast cancer.
AB  - Single nucleotide polymorphism (SNP) rs17849071 was recently reported to be
      inversely associated with PIK3CA amplification in follicular thyroid cancer, but
      the main function of this SNP remains unclear. In this study, by using PCR and
      sequencing method, we explored whether this SNP was associated with P53
      expression status and other clinicopathological characteristics in 62 Chinese
      breast cancer (BCa) patients. In our results, P53 protein accumulation was
      significantly associated with HER2 overexpression (P = 0.013) and Ki-67
      expression (P = 0.007), which were in accord with previous studies. Besides,
      there was a significantly inverse relationship between P53 protein expression and
      rs17849071 GT+GG genotype in Chinese BCa patients (P = 0.044). The SNP was not
      related to other important BCa markers such as estrogen receptor, progestin
      receptor, and HER2. Among different BCa intrinsic subtypes, no significant
      differences were found on P53 expression status (P = 0.356) or rs17849071
      polymorphism (T>G) (P = 0.813). In conclusion, SNP rs17849071 GT+GG genotype was
      inversely associated with P53 protein accumulation in BCa samples. Studies with
      larger sample size focusing on exploring the relationship of rs17849071
      polymorphisms, P53 accumulation, P53 mutations, and PIK3CA amplification might be
      needed.

PMID- 24908062
TI  - Low expression of novel lncRNA RP11-462C24.1 suggests a biomarker of poor
      prognosis in colorectal cancer.
AB  - Long noncoding RNAs (lncRNAs) have recently emerged as a major class of
      regulatory molecules, which were involved in a broad range of biological
      processes and complex diseases. Research on lncRNAs may shed light on
      tumorigenesis and progression of colorectal cancer (CRC). The purpose of the
      present study was to identify lncRNAs correlated with CRC and then investigate
      their potential functions. We selected 92 patients for this prospective study and
      then collected the tumor samples and clinical records. First, the global lncRNA
      expression profiles in tumor and adjacent normal tissues of patients with non
      metastatic CRC and patients with metastatic CRC were measured by microarray
      assay. Then, a noteworthy lncRNAs RP11-462C24.1 whose function was previously
      unknown was explored in detail on the aspect of the association of its expression
      level and clinicopathological features of CRC and patients' survival. We found
      that RP11-462C24.1 expression level was lower in cancer tissues compared with
      adjacent normal samples (P < 0.001). Furthermore, its expression level was lower
      in CRC patients with metastasis than those without metastasis (P = 0.049). That
      is, RP11-462C24.1 expression level decreased as the malignant degree of CRC
      increased. In addition, low expression of RP11-462C24.1 significantly correlated
      with more distant metastasis (P = 0.011). The areas under ROC curves were 0.78
      and 0.65 for RP11-462C24.1, distinguishing CRC from normal tissue and
      distinguishing CRC without metastasis from CRC with metastasis, respectively.
      Multivariate analysis identified that RP11-462C24.1 was an independent predictor
      for patients prognosis (P = 0.005). Furthermore, Kaplan-Meier analysis showed
      that patients with low expression of RP11-462C24.1 had a poor disease-free
      survival (P < 0.001). This is the first study that correlates RP11-462C24.1
      expression profile with malignancy grade in human CRC. Our results showed that
      RP11-462C24.1 could be a potential novel prognostic marker for CRC, and thus,
      provided a new strategy for CRC diagnosis. Meanwhile, our findings indicated the
      potential roles of RP11-462C24.1 in tumorigenesis and progression of CRC, which
      gave a clue for future studies.

PMID- 24908063
TI  - Epidemiology of post-transplant malignancy in Chinese renal transplant
      recipients: a single-center experience and literature review.
AB  - This study investigated the incidence and types of post-transplant malignancy in
      Chinese renal transplant recipients and the risk factors associated with
      malignancy. Data from 3,462 patients who underwent renal transplantation at
      Beijing Friendship Hospital were combined with data from 26 previous reports
      describing malignancy rates in 27,170 Chinese renal transplant recipients.
      Between 1974 and 2014, 179/3,462 (5.17 %) patients who underwent renal
      transplantation at our center developed malignancy. The most common site of
      malignancy was the urinary system, and the most common type was urothelial
      transitional cell carcinoma. Combined data from our center and previous reports
      showed malignancy in 671 (2.19 %) Chinese renal transplant recipients. The ten
      most common malignancies were urothelial transitional cell carcinoma (n = 283),
      hepatocellular carcinoma (n = 68), gastrointestinal cancer (n = 63), renal cell
      carcinoma (n = 42), lymphoma (n = 42), lung cancer (n = 28), breast cancer (n =
      19), skin cancer (n = 18), Kaposi's sarcoma (n = 12), and cervical cancer (n =
      10). The incidence of post-transplant malignancy in renal transplant recipients
      was lower in China than the reported rates in other countries, and the most
      common sites of malignancy were the urinary and digestive system. The relative
      frequency of malignancy sites differed between northern and southern China. Renal
      transplant recipients on long-term immunosuppressive therapy should receive
      careful follow-up, including annual or biannual screening for malignancy in high
      risk individuals.

PMID- 24908064
TI  - A novel point mutation in exon 20 of EGFR showed sensitivity to erlotinib.
AB  - Mutations of epidermal growth factor receptor (EGFR) gene are good predictors of
      response to treatment with EGFR tyrosine kinase inhibitors (TKIs) for non-small
      cell lung cancer (NSCLC). It is well established that classic mutations, such as
      in-frame deletions in exon 19 and the point mutation L858R in exon 21, are
      associated with high sensitivity to EGFR TKIs. Though mutations in exon 20 are
      almost correlated with EGFR-TKIs resistance, the awareness that they might confer
      sensitivity to TKI treatment should be emphasized. Herein, we describe a novel
      mutation in exon 20 of EGFR in a Chinese male non-smoker, who was diagnosed with
      stage IV lung adenocarcinoma and characterized by the codon 769 point mutation
      GTG>GCG, which translates into alanine instead of valine (p.V769A). In this case,
      the patient showed a good clinical response to erlotinib after
      paclitaxel/cisplatin first-line and docetaxel second-line chemotherapies.
      Therefore, we suggest that this rare mutation (p.V769A) may be a sensitive EGFR
      mutation in NSCLC. The identification of novel EGFR mutations provides new
      predictive biomarkers for TKI treatment and is essential to the successful use of
      targeted therapies. 

PMID- 24908065
TI  - Advanced thyroid cancers: new era of treatment.
AB  - Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid
      carcinomas, the research for new therapies is fundamental. Clinical trials of
      many tyrosine kinase inhibitors as well as anti-angiogenic inhibitors suggest
      that patients with thyroid cancer could have an advantage with new target
      therapy. Recently, Food and Drug Administration approved two targeted therapies,
      vandetanib and cabozantinib for the treatment of metastatic thyroid carcinomas
      with acceptable outcome. We summarized the results and the toxic effects
      associated with these treatments reported in clinical trials. Future trials
      should aim at combinations of targeted agents with or without other treatment
      modalities to obtain a more effective result in thyroid carcinoma treatment. 

PMID- 24908066
TI  - Clinical values of selective-clamp technique in robotic partial nephrectomy.
AB  - PURPOSE: In the era of robotic partial nephrectomy (RPN), several efforts on
      improved renal functional outcome have been reported. Selective-clamp is a novel
      technique that eliminates global ischemia, the clinical value of which needs to
      be demonstrated. The purpose of this study was to compare the postoperative
      functional outcomes of patients who underwent selective-clamp and total-clamping
      RPN. PATIENTS AND METHODS: From February 2009 to October 2012, a database of 126
      consecutive patients who underwent RPN was retrospectively analyzed, 117 patients
      met our inclusion criteria and were stratified into two groups, 20 patients
      underwent selective-clamp RPN, and 97 patients underwent total-clamping RPN. Post
      hoc power analysis was subsequently performed for calculation of sufficient
      sample size. Demographics/tumor characteristics, functional outcomes and
      complications were analyzed. RESULTS: All selective-clamp RPN cases were
      successfully performed. Mean tumor size was 3.4 cm [standard deviation (SD): +/
      1.4], mean RENAL nephrometry score was 7.3 (SD: +/-2.0), and no Clavien-Dindo III
      V complications were recorded. Selective-clamp RPN group had a significantly
      lower percentage decrease in the postoperative estimated glomerular filtration
      rate at 1 week (1.8 vs. 20.8 ml/min/1.73 m(2), p = 0.001) and 3 months (0 vs. 9.9
      ml/min/1.73 m(2), p = 0.032) when compared with the total-clamping RPN group.
      There were no significant differences in surgical margin and complication rates.
      CONCLUSIONS: Selective-clamp confers improved renal functional outcomes in
      comparison to total-clamping RPN, with acceptable complications and oncological
      outcomes even in large and complex tumors.

PMID- 24908067
TI  - Random biopsy: when, how many and where to take the cores?
AB  - PURPOSE: The optimal random prostate biopsy scheme (PBx) in the initial and
      repeated setting is still an issue of controversy. We performed an analysis of
      the recent literature about the prostate biopsy techniques. METHODS: We performed
      a clinical and critical literature review by searching MEDLINE database from
      January 2005 up to January 2014. Electronic searches were limited to the English
      language, and the keywords prostate cancer, prostate biopsy, transrectal
      ultrasound, transperineal prostate biopsy were used. RESULTS: Prostate biopsy
      strategy in initial setting. According to the literature and the major
      international guidelines, the recommended approach in initial setting is still
      the extended scheme (EPBx) (12 cores). However, there is now a growing evidence
      in the literature that (a) saturation PBx (>20 cores) (SPBx) might be indicated
      in patients with PSA <10 ng/ml or low PSA density or large prostate and (b) an
      individualized approach with more than 12 cores according to the clinical
      characteristics of the patients may optimize cancer detection in the single
      patient. Moreover, in the era of multi-parametric MRI (mpMRI), EPBx or SPBX may
      be substituted by mpMRI-targeted biopsies that have demonstrated superiority over
      systematic random biopsies for the detection of clinically significant disease
      and representation of disease burden, while deploying fewer cores. Prostate
      biopsy strategy in repeat setting. How and how many cores should be taken in the
      different scenarios in the repeated setting is still unclear. SPBx clearly
      improves cancer detection if clinical suspicion persists after previous biopsy
      with negative findings and is able to provide an accurate prediction of prostate
      tumour volume and grade. Nevertheless, international guidelines do not strongly
      recommended SPBx in all situations of repeated setting. In the active
      surveillance and in focal therapy protocols, the optimal schemes have to be
      defined. CONCLUSIONS: The course of PBx has changed significantly from sextant
      biopsies to systematic and from extended to SPBx schemes. The issue about the
      number and location of the cores is still a matter of debate both in initial and
      in repeat setting. At present, EPBx is sufficient in most of the cases to provide
      adequate diagnosis and prostate cancer characterization in the initial setting,
      while SPBx seems to be necessary in repeat setting. The PBx schemes are evolving
      also because the scenario in which a PBx is necessary is changing. Random
      prostate PBx do not represent the future, while imaging target biopsy are
      becoming more popular.

PMID- 24908068
TI  - Usefulness of KL-6 in the subtyping of intraductal papillary mucinous neoplasia
      of the pancreas, including carcinoma, dysplasia, and hyperplasia.
AB  - KL-6 is known as a useful serum biomarker of the disease activity in interstitial
      pneumonias. We investigated its usefulness as a biomarker for subtyping
      intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. IPMNs are
      generally divided into 4 subtypes, namely pancreatobiliary (PB), intestinal
      (INT), gastric (GS), and oncocytic (ONC). Aside from the KL-6 antibody, the MUC1,
      MUC2, MUC5AC, MUC6, and MIB-1 antibodies were also examined. Eighteen IPMN cases
      were examined, including 12 cases of intraductal papillary mucinous carcinomas
      (IPMCs) simultaneously associated with dysplasia (IPMDs) and hyperplasia (IPMHs)
      and 6 IPMD cases with IPMH. KL-6 antibody was positive in the 8 IPMC cases,
      corresponding to a MUC2-negative PB subtype, but negative in 4 IPMC cases,
      corresponding to the INT subtype, which is positive for MUC2. IPMD of moderate-to
      severe degree positively stained for the KL-6 antibody in the IPMC cases of the
      PB subtype but not in those of the INT subtype. The IPMH cases were mostly
      negative for KL-6, similar to the mild IPMD cases. In the 6 cases of mild IPMD
      and/or IPMH, KL-6 and MUC2 expressions were mostly negative. In conclusion, the
      KL-6 antibody is immunohistochemically a good biomarker of the PB subtype of
      IPMC, but not the INT subtype. Identifying IPMN subtypes based on KL-6
      stainability would be useful. Clinicopathological studies with more IPMC cases
      might be needed for further progress in this field of study. 

PMID- 24908069
TI  - Menstrual cyclic change of metastin/GPR54 in endometrium.
AB  - Metastin/kisspeptin is encoded by KISS1 and functions as an endogenous ligand of
      GPR54. Interaction of metastin with GPR54 suppresses metastasis and also
      regulates release of gonadotropin-releasing hormone, which promotes secretion of
      estradiol (E2) and progesterone (P4). We have previously demonstrated epigenetic
      regulation of GPR54 in endometrial cancer and the potent role of metastin
      peptides in inhibiting metastasis in endometrial cancer. However, little is known
      about how the metastin-GPR54 axis is regulated in the endometrium, the precursor
      tissue of endometrial cancer. Endometrial stromal cells (ESCs) and endometrial
      glandular cells (EGCs) within the endometrium show morphological changes when
      exposed to E2 and P4. In this study, we show that metastin expression is induced
      in ESCs through decidualization, but is repressed in glandular components of
      atypical endometrial hyperplasia (AEH) and endometrial cancer relative to EGCs.
      The promoter of GPR54 is unmethylated in normal endometrium and in AEH. These
      results indicate metastin may function in decidualized endometrium to prepare for
      adequate placentation but this autocrine secretion of metastin is deregulated
      during oncogenesis to enable tumor cells to spread. 

PMID- 24908070
TI  - Sophono Alpha System and subtotal petrosectomy with external auditory canal blind
      sac closure.
AB  - Recently, a new acoustic device, the so-called Sophono Alpha System, has been
      introduced into clinical practice. The aim of this study was to assess Sophono
      Alpha System hearing aids in ten patients suffering from recurrent chronic middle
      ear disease who underwent subtotal petrosectomy. Presence of mixed hearing loss
      with bone conduction thresholds better than or equal to 45 dB was present in each
      patient. Audiometric tests were performed before and after Sophono implantation
      and using a conventional bone conduction hearing aid (hearing glasses). Speech
      audiometry data (speech recognition threshold and word recognition score) were
      also collected. Speech recognition threshold in dB and percentage of word
      recognition score at 65 dB were subsequently calculated. After implantation and
      activation of the Sophono Alpha System, audiological data showed an average air
      conduction value of 42.1 dB. By comparing this data with the values of air
      conduction following subtotal petrosectomy, an average acoustic improvement of
      29.7 dB could be calculated. The hearing results showed significantly better
      outcomes of Sophono Alpha System vs. conventional bone conduction aid.
      Indications to MRI use in patients undergoing Sophono Alpha System implantation
      are also provided.

PMID- 24908071
TI  - ADAM33 polymorphisms and susceptibility to allergic rhinitis: a meta-analysis.
AB  - Several polymorphisms in a disintegrin and metalloproteinase 33 (ADAM33) have
      been implicated in susceptibility to allergic rhinitis (AR), but the results are
      inconclusive. This meta-analysis was aimed to clarify the impact of ADAM33
      polymorphisms on AR risk. Pubmed, EMBASE and Cochrane library were searched until
      11 October 2013 for eligible studies on seven ADAM33 polymorphisms: T1, T2, S1,
      S2, V4, Q-1 and T+1. Data were extracted, and pooled odd ratios (ORs) as well as
      95 % confidence intervals (CIs) were calculated. Six studies with 1,135 AR
      patients and 1,565 controls were included. It was found that ADAM33 T1 (AG+GG vs.
      AA, OR 1.47, 95 % CI 1.23-1.75, I (2) = 94 %; G vs. A, OR 1.53, 95 % CI 1.32
      1.78, I (2) = 94 %), T2 (GA+AA vs. GG, OR 1.26, 95 % CI 1.06-1.51, I (2) = 92 %;
      G vs. A, OR 1.27, 95 % CI 1.08-1.50, I (2) = 92 %), V4 (CG+GG vs. CC OR 1.35, 95
      % CI 1.14-1.59, I (2) = 95 %;G vs. C OR 1.28, 95 % CI 1.13-1.44, I (2) = 96 %)
      and Q-1 (GA+AA vs. GG OR 1.55, 95 % CI 1.24-1.95, I (2) = 74 %; G vs. C OR 1.46,
      95 % CI 1.19-1.79, I (2) = 73 %) polymorphisms were significantly associated with
      AR susceptibility but not S1, S2 and T+1. In Asians, the same result was found.
      This meta-analysis indicated that ADAM33 T1, T2, V4 and Q-1 polymorphisms may be
      the risk factors which conferred to AR susceptibility. The differences in
      ethnicity did not influence the associations obviously. Gene-gene and gene
      environment interactions should be investigated in the future.

PMID- 24908072
TI  - Bacillus thermophilum sp. nov., isolated from a microbial fuel cell.
AB  - A novel thermophilic, Gram-staining positive bacterium, designated DX-2(T), was
      isolated from the anode biofilm of a microbial fuel cell. Cells of the strain
      were oxidase positive, catalase positive, facultative anaerobic, motile rods. The
      isolate grew at 30-60  degrees C (optimum 50  degrees C) and pH 5-9 (optimum pH 8
      8.5). The pairwise 16S rRNA gene sequence similarities showed that strain DX-2(T)
      was most closely related to Bacillus fumarioli LMG 17489(T) (96.2 %), B. firmus
      JCM 2512(T) (96.0 %) and B. foraminis DSM 19613(T) (95.7 %). Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain DX-2(T) formed a
      cluster with B. smithii (95.5 %) and B. infernus (94.9 %). The genomic G+C
      content of DX-2(T) was 43.7 mol%. The predominant respiratory quinone was MK-7.
      The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and unknown phospholipids. The major cellular fatty acid
      was iso-C16:0. Based on its phenotypic characteristics, chemotaxonomic features,
      and results of phylogenetic analysis, the strain was identified to represent a
      distinct novel species in the genus Bacillus, and the name proposed is B.
      thermophilum sp. nov. The type strain is DX-2(T) (=CCTCC AB2012194(T) = KCTC
      33128(T)). 

PMID- 24908073
TI  - Candida pruni sp. nov. is a new yeast species with antagonistic potential against
      brown rot of peaches.
AB  - Brown rot caused by Monilinia spp. is among the most important postharvest
      diseases of commercially grown stone fruits, and application of antagonistic
      yeasts to control brown rot is one promising strategy alternative to chemical
      fungicides. In this research, new yeast strains were isolated and tested for
      their activity against peach brown rot caused by Monilinia fructicola. Three
      yeast strains were originally isolated from the surface of plums (cv Chinese
      Angelino) collected in the north of China. In artificially wounded inoculation
      tests, the yeast reduced the brown rot incidence to 20 %. The population of the
      yeast within inoculated wounds on peaches significantly increased at 25  degrees
      C from an initial level of 5.0*10(6) to 4.45*10(7) CFU per wound after 1 day. The
      antagonistic strains were belonging to a new species of the genus Candida by
      sequence comparisons of 26 S rDNA D1/D2 domain and internal transcribed spacer
      region. The strains are most closely related to C. asparagi, C. musae and C.
      fructus on the basis of the phylogenetic trees based on the D1/D2 region of 26S
      rDNA. However, the strains are notably different from C. asparagi, C. musae and
      C. fructus, in morphological and physiological characteristics. Therefore, the
      name Candida pruni is proposed for the novel species, with sp-Quan
      (=CBS12814T=KCTC 27526T=GCMC 6582T) as the type strain. Our study showed that
      Candida pruni is a novel yeast species with potential biocontrol against brown
      rot caused by M. fructicola on peaches.

PMID- 24908074
TI  - Motor imagery practice may compensate for the slowdown of sensorimotor processes
      induced by short-term upper-limb immobilization.
AB  - Recently, it has been demonstrated that sensorimotor representations are quickly
      updated following a brief period of limb non-use. The present study examined the
      potential of motor imagery practice (MIP) and investigated the role of motor
      imagery instructions (kinesthetic vs. visual imagery) to counteract the
      functional impairment induced by sensorimotor restriction. The participants were
      divided into four groups. Three groups wore a splint on their left hand for 24 h.
      Prior to the splint removal, two of the three groups performed 15 min of MIP,
      with kinesthetic or visual modalities (KinMIP and VisMIP groups, respectively).
      The third group did not practice motor imagery (NoMIP group). Immediately after
      the splint removal, the participants were assessed using a hand laterality task
      known for evaluating sensorimotor processes. A fourth group served as the control
      (i.e., without immobilization and MIP). The main results showed slower left-hand
      response times for the immobilized NoMIP group compared with the controls.
      Importantly, faster response times for the left-hand stimuli appeared for the
      KinMIP groups only compared with the NoMIP group. No difference between the four
      groups was observed for the right-hand stimuli. Overall, these results
      highlighted the somatotopic effect of limb non-use on the efficiency of
      sensorimotor processes. Importantly, the slowdown of the sensorimotor processes
      induced by 24 h of sensorimotor deprivation may be counteracted by a kinesthetic
      MIP, whereas no beneficial effect appeared with visual imagery. We discuss the
      importance of imagery modalities for sensorimotor reactivation. 

PMID- 24908075
TI  - The coding of repetitions and alternations in action sequences: spatial or
      relational?
AB  - We used variants of the Simon task to investigate whether repetitions and
      alternations in short keypress sequences are represented by spatial or relational
      codes. With spatial coding, either absolute or relative location would be used
      for coding the second response in a sequence. With relational coding, the second
      response would be coded in terms of a non-spatial relation to the first one
      (e.g., left response-same response, for a repetition). In three experiments with
      different imperative stimuli, we compared Simon effects across three experimental
      conditions, a single-response condition, a response-repetition condition (each
      stimulus required two keypresses on the same side, e.g., left-left), and a
      response-alternation condition (each stimulus required a keypress on each side,
      e.g., left-right). When compared to the single-response condition, spatial coding
      of the second response should modulate the Simon effect (i.e., response conflict)
      in selecting the first response because spatial coding of the second response
      produces additional dimensional overlap of stimulus and the second-response code.
      We observed Simon effects in the response times of first responses in each
      condition, and they increased in the response-alternation condition, but not in
      the response-repetition condition. The findings suggest relational coding of
      response repetitions, and spatial coding of response alternations. 

PMID- 24908076
TI  - Expression of liver-targeting peptide modified recombinant human endostatin and
      preliminary study of its biological activities.
AB  - Recombinant human endostatin (rEndostatin or endostar) has been shown to inhibit
      endothelial cells proliferation, migration, and angiogenesis and exhibits a broad
      spectrum of activities against solid tumors. However, rEndostatin is easily
      degradable and evenly distributed to all tissues. Selectively delivering
      rEndostatin to the lesion site might be more potent. The circumsporozoite protein
      (CSP) coats the malarial sporozoite and targets the liver for infection; I-plus
      of N end of CSP could specifically bind to the liver. Based on this, we
      hypothesize the fusion protein with introducing the CSP I-plus sequence into
      rEndostatin (rES-CSP) of which not only targets the liver, but also inhibits
      endothelial cells proliferation, migration, and tube formation. Therefore, it
      selectively reduces angiogenesis of hepatocellular carcinoma (HCC) and improves
      the anti-HCC effect. In this study, we synthesized a novel rES-CSP fusion gene by
      SOE-PCR and expressed the fusion protein in Escherichia coli BL2l (DE3). The
      suitable conditions were optimized by an orthogonal test (L(25)(5)(4)). The
      yields were 12 mg/l culture medium following refolding and purification on nickel
      nitrilotriacetic acid (Ni-NTA) metal affinity chromatography matrices. The
      purified rES-CSP is specifically targeted to the hepatocyte and inhibited the
      proliferation and migration of human umbilical vein endothelial cells (HUVECs) in
      a dose-dependent manner and showed potent antiangiogenic capability on HUVECs
      tube formation assay and chick embryo chorioallantoic membrane (CAM) assay. These
      results lay the foundation for the further study of its targeting and anti-HCC in
      vivo and provide a feasible and convenient approach to produce liver-targeting
      drugs for treatment of the liver diseases. 

PMID- 24908077
TI  - The value of our care.

PMID- 24908079
TI  - Variation of the number of proximal caudal vertebrae with tail reduction in Old
      World monkeys.
AB  - Tail length in primates can vary greatly between species or even between local
      conspecific populations, and the tail is markedly reduced in several lineages. In
      Old World monkeys, tail length is considered as an important feature reflecting
      their phylogeny and adaptations. The number of caudal vertebrae is one of the
      important factors which determine tail length, and it is known that this number
      varies with tail length. Caudal vertebrae can be divided into two types (proximal
      and distal), and tail mobility and function are considered to be different in
      these two regions. Though the number of vertebrae in each region is important for
      understanding tail length evolution in Old World monkeys, there have been few
      attempts to investigate this matter. This study focused only on the proximal
      caudal vertebrae, which are more easily preserved than the distal ones, and
      tested if there is variation in their number with tail length or phylogenic
      differences. As a result, two important findings were obtained: (1) the variation
      of the number of proximal caudal vertebrae was different among the phylogenic
      groups, and (2) especially in Papionini, there was a great variation in the
      number of proximal caudal vertebrae, and it correlated strongly with relative
      tail length [RTL = (tail length/head and body length (sitting height)) * 100%]. I
      speculate that these variations in the number of proximal caudal vertebrae were
      possibly caused by a change of the embryonic developmental mechanism of tail
      morphogenesis, a common mechanism of morphological evolution. To clarify the
      mechanisms and evolutionary trends of the variation in the proximal caudal
      vertebrae, not only morphological approaches but also developmental biological
      approaches will be necessary in the future.

PMID- 24908078
TI  - Infection routes matter in population-specific responses of the red flour beetle
      to the entomopathogen Bacillus thuringiensis.
AB  - BACKGROUND: Pathogens can infect their hosts through different routes. For
      studying the consequences for host resistance, we here used the entomopathogen
      Bacillus thuringiensis and the red flour beetle Tribolium castaneum for oral and
      systemic (i. e. pricking the cuticle) experimental infection. In order to
      characterize the molecular mechanisms underpinning the two different infection
      routes, the transcriptomes of beetles of two different T. castaneum populations-
      one recently collected population (Cro1) and a commonly used laboratory strain
      (SB)--were analyzed using a next generation RNA sequencing approach. RESULTS: The
      genetically more diverse population Cro1 showed a significantly larger number of
      differentially expressed genes. While both populations exhibited similar
      reactions to pricking, their expression patterns in response to oral infection
      differed remarkably. In particular, the Cro1 population showed a strong response
      of cuticular proteins and developmental genes, which might indicate an adaptive
      developmental flexibility that was lost in the SB population presumably as a
      result of inbreeding. The immune response of SB was primarily based on
      antimicrobial peptides, while Cro1 relied on responses mediated by phenoloxidase
      and reactive oxygen species, which may explain the higher resistance of this
      strain against oral infection. CONCLUSIONS: Our data demonstrate that
      immunological and physiological processes underpinning the two different routes
      of infection are clearly distinct, and that host populations particularly differ
      in responses to oral infection. Furthermore, gene expression upon pricking
      infection entailed a strong signal of wounding, highlighting the importance of
      pricking controls in future infection studies.

PMID- 24908081
TI  - Repeated phase shifts in the lighting regimen change the blood pressure response
      to norepinephrine stimulation in rats.
AB  - Disturbed circadian activity of the sympathetic system may be involved in
      negative consequences of chronodisruption on the cardiovascular system. We
      studied daily changes in pressure response to adrenergic stimulation in rats
      exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood
      pressure (BP), heart rate (HR) and locomotor activity was measured by
      radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h
      shifts per week) lasting for 12 weeks. Norepinephrine was administered
      subcutaneously in the middle of L and D during week 12 of PAS exposure. In the
      control LD cycle, cardiovascular parameters exhibited significant daily rhythms
      with expected higher values during D than L phase. Rats exposed to PAS showed
      disturbed rhythms without a BP and HR increase. Administration of norepinephrine
      to control rats revealed daily variability in the cardiovascular response with
      higher stimulation of BP during L than D. This daily pattern of BP response to
      norepinephrine was diminished in the PAS group. The damped daily variability in
      pressure response to norepinephrine and augmented response during the light phase
      of the day suggest that the increased and desynchronized activity of the
      sympathetic system may worsen responses of the cardiovascular system to load in
      individuals exposed to irregular LD conditions. 

PMID- 24908080
TI  - Sterol regulatory element binding protein 2 overexpression is associated with
      reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously
      hypertensive rats.
AB  - It has been reported that the major function of the sterol regulatory element
      binding protein 2 (SREBP-2) is to activate preferentially cholesterol
      biosynthesis in liver and adipose tissue rather than fatty acid synthesis. In the
      current study, we analyzed the effects of overexpression of human dominant
      positive SREBP-2 transgene under control of PEPCK promoter in the spontaneously
      hypertensive rat (SHR) on lipid and glucose metabolism. Transgenic overexpression
      of SREBP-2 was associated with significantly higher hepatic triglycerides (20.4+/
      0.9 vs. 17.0+/-0.05 micromol/g, P<0.05) but not cholesterol (10.6+/-0.4 vs.
      10.9+/-0.4 micromol/g) and decreased relative weight of epididymal fat pad
      (0.73+/-0.03 vs. 0.83+/-0.03, P<0.05). In addition, muscle triglyceride (15.8+/
      3.7 vs. 8.5+/-1.2 micromol/g, P<0.001) and cholesterol (3.6+/-0.5 vs. 2.1+/-0.1
      micromol/g, P<0.05) concentrations were significantly increased in transgenic
      rats when compared to SHR controls. Ectopic fat accumulation was associated with
      significantly increased serum glucose levels (6.4+/-0.1 vs. 5.9+/-0.1 mmol/l,
      P<0.005) and reduced insulin levels (1.78+/-0.33 vs. 2.73+/-0.37 nmol/l, P<0.05)
      in transgenic rats. These results provide evidence for important role of SREBP-2
      in regulation of lipid and glucose metabolism. 

PMID- 24908082
TI  - Activation of HPA axis and remodeling of body chemical composition in response to
      an intense and exhaustive exercise in C57BL/6 mice.
AB  - Several deleterious effects may occur when intense and exhaustive exercise (IE)
      is not well-planned. This study aimed to investigate the effects of a short
      duration IE on body chemical composition and hypothalamic-pituitary-adrenal (HPA)
      axis. C57Bl/6 mice were distributed into four groups (10 mice per group): control
      (C-4D and C-10D), 4 days (E-4D), and 10 days of IE (E-10D). IE program consisted
      of a daily running session at 85 % of maximum speed until the animal reached
      exhaustion. Body weight as well as total body water, fat and protein content were
      determined from animal carcasses. HPA activation was assessed by plasma
      corticosterone levels measured by radioimmunoassay and the weight of both the
      adrenal glands and thymus were measured. Plasma corticosterone levels increased
      by 64 % in both the E-4D and E-10D groups. The weight of the adrenal glands
      augmented by 74 % and 45 %, at 4 and 10 days of IE, respectively, whereas thymus
      weight diminished by 15 % only in the E-10D group. The total carcass fat content
      decreased by 20 % only at 4 days IE, whereas protein content decreased by 20 % in
      both E-4D and E-10D groups. A relationship between corticosterone plasma levels
      and loss of body protein content in both E-4D and E-10D groups was observed
      (R(2)=0.999). We concluded that IE may be related to HPA axis activation
      associated with remodeling of body chemical composition in C57BL/6 mice. 

PMID- 24908083
TI  - Severity of lethal ischemia/reperfusion injury in rat hearts subjected to
      ischemic preconditioning is increased under conditions of simulated
      hyperglycemia.
AB  - The aim of our study was to characterize resistance to ischemia/reperfusion (I/R)
      injury in Langendorff-perfused rat hearts and effectivity of ischemic
      preconditioning (PC) under condition of simulated acute hyperglycemia (SAHG) by
      perfusion of the hearts with Krebs-Henseleit (KH) solution with elevated glucose
      concentration (22 mmol/l). I/R injury was induced by 30-min coronary occlusion
      followed by 120-min reperfusion and PC by two cycles of 5-min occlusion/5-min
      reperfusion, prior to I/R. The severity of I/R injury was characterized by
      determination of the size of infarction (IS, expressed in % of area at risk size)
      and the amount of heart-type fatty acid binding protein (h-FABP, a marker of cell
      injury) released from the hearts to the effluent. Significantly smaller IS (8.8+/
      1 %) and lower total amount of released h-FABP (1808+/-660 pmol) in PC group
      compared with IS 17.1+/-1.2 % (p<0.01) and amount of h-FABP (8803+/-2415 pmol,
      p<0.05) in the non-PC control hearts perfused with standard KH solution (glucose
      11 mmol/l) confirmed protective effects of PC. In contrast, in SAHG groups, PC
      enhanced IS (21.4+/-2.2 vs. 14.3+/-1.3 %, p<0.05) and increased total amount of h
      FABP (5541+/-229 vs. 3458+/-283 pmol, p<0.05) compared with respective non-PC
      controls. Results suggest that PC has negative effect on resistance of the hearts
      to I/R injury under conditions of elevated glucose in vitro. 

PMID- 24908084
TI  - Evidence of euryhalinity of the Gulf corvina (Cynoscion othonopterus).
AB  - The effects of environmental salinity on physiological responses, growth, and
      survival of the Gulf corvina, C. othonopterus, were evaluated in a 6-week
      completely randomized design experiment. Corvina (17.2+/-2.3 g mean initial body
      weight) were subjected to salinities of 5, 15, 25, and 35 0/00 and fed a
      commercial feed with protein and lipid contents of 46 and 14 %, respectively.
      Plasma osmolality increased significantly with salinity, ranging from 335.1+/-5.3
      mOsm/kg in fish maintained at 5 0/00, to 354.8+/-6.8 mOsm/kg in fish kept in
      seawater, while a significant inverse relationship was observed between salinity
      and moisture content of whole fish, ranging from 73.8+/-0.7 (measured at 5 0/00)
      to 76.9+/-1.0 % (measured at 35 0/00). In spite of this, growth indices (final
      weight, weight gain, specific growth rate, condition factor, survival) were not
      altered, suggesting that, like other members of the family Sciaenidae, the Gulf
      corvina is a strong osmoregulator. The isosmotic point for this species was
      estimated to correspond to a salinity of 9.8 0/00. The present study represents
      the first set of experimental data on salinity tolerance of C. othonopterus and
      confirms the euryhalinity of this species. 

PMID- 24908085
TI  - Protective effect of ginsenoside against acute renal failure via reduction of
      renal oxidative stress and enhanced expression of ChAT in the proximal convoluted
      tubule and ERK1/2 in the paraventricular nuclei.
AB  - Generation of reactive oxygen species significantly contributes to the
      pathogenesis of acute renal failure (ARF) induced by myoglobin release.
      Ginsenosides (GS), the principal active ingredients of ginseng, is considered as
      an extremely good antioxidative composition of Chinese traditional and herbal
      drugs. The purpose of the present study was to investigate the protective effect
      of ginsenoside in rats with ARF on the changes of cholinergic nervous system in
      the kidney as well as on the involvement of mitogen-activated protein kinases
      (MAPK) in the hypothalamic paraventricular nuclei (PVN). In our assay, glycerol
      induced acute renal failure in rats was employed to study the protective effects
      of ginsenoside. Our results indicated that the treatment of ARF rats with
      ginsenosides for 48 h significantly reduced lipid peroxidation, restored the
      superoxide dismutase (SOD) level. Meanwhile, the obvious increase of choline
      acetyltransferase-immunoreactivity (ChAT-IR) in the proximal convoluted tubular
      cells (PCT) was observed by immunohistochemistry in ARF+GS group. The same effect
      was also observed in the changes of p-ERK1/2-IR in the hypothalamic
      paraventricular nuclei. Our results suggest that ginsenoside administered orally
      may have a strong renal protective effect against glycerol-induced ARF, reduce
      the renal oxidative stress, and ginsenoside can also activate the cholinergic
      system in PCT, simultaneously MAPK signal pathway in the PVN was also activated. 

PMID- 24908086
TI  - Oxidative stress and Down syndrome. Do antioxidants play a role in therapy?
AB  - Oxidative stress is a phenomenon associated with imbalance between production of
      free radicals and reactive metabolites (e.g. superoxide and hydrogen peroxide)
      and the antioxidant defences. Oxidative stress in individuals with Down syndrome
      (DS) has been associated with trisomy of the 21st chromosome resulting in DS
      phenotype as well as with various morphological abnormalities, immune disorders,
      intellectual disability, premature aging and other biochemical abnormalities.
      Trisomy 21 in patients with DS results in increased activity of an important
      antioxidant enzyme Cu/Zn superoxide dismutase (SOD) which gene is located on the
      21st chromosome along with other proteins such as transcription factor Ets-2,
      stress inducing factors (DSCR1) and precursor of beta-amyloid protein responsible
      for the formation of amyloid plaques in Alzheimer disease. Mentioned proteins are
      involved in the management of mitochondrial function, thereby promoting
      mitochondrial theory of aging also in people with DS. In defence against toxic
      effects of free radicals and their metabolites organism has built antioxidant
      defence systems. Their lack and reduced function increases oxidative stress
      resulting in disruption of the structure of important biomolecules, such as
      proteins, lipids and nucleic acids. This leads to their dysfunctions affecting
      pathophysiology of organs and the whole organism. This paper examines the impact
      of antioxidant interventions as well as positive effect of physical exercise on
      cognitive and learning disabilities of individuals with DS. Potential therapeutic
      targets on the molecular level (oxidative stress markers, gene for DYRK1A,
      neutrophic factor BDNF) after intervention of natural polyphenols are also
      discussed.

PMID- 24908087
TI  - An updated view of leptin on implantation and pregnancy: a review.
AB  - The hormone leptin, which is thought to be primarily produced by adipose tissue,
      is a polypeptide that was initially characterized by its ability to regulate food
      intake and energy metabolism. Leptin appears to signal the status of body energy
      stores to the brain, resulting in the regulation of food intake and whole-body
      energy expenditure. Subsequently, it was recognized as a cytokine with a wide
      range of peripheral actions and is involved in the regulation of a number of
      physiological systems including reproduction. In the fed state, leptin circulates
      in the plasma in proportion to body adiposity in all species studied to date.
      However other factors such as sex, age, body mass index (BMI), sex steroids and
      pregnancy may also affect leptin levels in plasma. In pregnant mice and humans,
      the placenta is also a major site of leptin expression. Leptin circulates in
      biological fluids both as free protein and in a form that is bound to the soluble
      isoform of its receptor or other binding proteins such as one of the
      immunoglobulin superfamily members Siglec-6 (OB-BP1). Although the actions of
      leptin in the control of reproductive function are thought to be exerted mainly
      via the hypothalamic-pituitary-gonadal axis, there have also been reports of
      local direct effects of leptin at the peripheral level, however, these data
      appear contradictory. Therefore, there is a need to summarize the current status
      of research outcomes and analyze the possible reasons for differing results and
      thus provide researchers with new insight in designing experiments to investigate
      leptin effect on reproduction. Most importantly, our recent experimental data
      suggesting that reproductive performance is improved by decreasing concentrations
      of peripheral leptin was unexpected and cannot be explained by hypotheses drawn
      from the experiments of excessive exogenous leptin administration to normal
      animals or ob/ob mice. 

PMID- 24908088
TI  - Protection of dopamine neurons by vibration training and up-regulation of brain
      derived neurotrophic factor in a MPTP mouse model of Parkinson's disease.
AB  - It is unknown whether the longer duration of vibration training (VT) has a
      beneficial effect on Parkinson's disease (PD). And also, the mechanisms
      underlying the reported sensorimotor-improvement in PD induced by short-duration
      of VT has not been determined. Here, we investigated the effects of longer
      duration (4 weeks) of low amplitude vibration (LAV) training on the numbers of
      dopaminergic neurons in the substantia nigra by immunostaining and the levels of
      dopamine (DA) and brain-derived neurotrophic factor (BDNF) in the striatum by
      HPLC and ELISA in the chronic MPTP lesion mouse. We demonstrated for the first
      time that the longer duration of VT could significantly increase the numbers of
      nigrostriatal DA neurons and the contents of striatal DA and BDNF in the MPTP
      mice. Our findings implied that longer duration of VT could protect dopaminergic
      neurons from the MPTP-induced damage probably by upregulating BDNF and also
      provided evidence for the beneficial effect of longer duration of VT on PD at the
      cellular and molecular level. 

PMID- 24908090
TI  - Reverse transport of cholesterol is the reason for resistance to development of
      atherosclerosis in Prague Hereditary Hypercholesterolemic (PHHC) rat.
AB  - The Prague Hereditary Hypercholesterolemic (PHHC) rat is a model of
      hypercholesterolemia. In previous experiments, it was found to be completely
      resistant to the development of atherosclerosis. It was assumed that the reverse
      transport of cholesterol (RCT) might be the reason for this resistance. In this
      study, RCT was measured in vivo by cholesterol efflux from macrophages to plasma,
      using previously established methods for RCT in mice (Rader 2003), optimized for
      measurements in rats. Primary cell culture of macrophages was labeled with (14)C
      cholesterol and then injected intraperitoneally into rats. Plasma and feces were
      collected at 24 and 48 h. The plasma (14)C-cholesterol levels at both 24 and 48 h
      were significantly higher in male PHHC rats compared to control Wistar rats. The
      PHHC rats excreted less (14)C-cholesterol in feces in 24 and 48 h compared to
      Wistar rats. The largest pool of (14)C-cholesterol was found in the adipose
      tissue of PHHC rats and in contrast lower levels of (14)C-cholesterol were
      measured in the liver and muscle tissues of PHHC rats compared with Wistar rats.
      Increasing release of (14)C-cholesterol efflux from macrophages demonstrates
      accelerated RTC and leads to prevention of atherogenesis in PHHC rats. 

PMID- 24908089
TI  - Effect of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, on
      behavioral and physiological parameters.
AB  - The role of brain derived nitric oxide in the physiology and behavior remains
      disputable. One of the reasons of the controversies might be systemic side
      effects of nitric oxide synthase inhibitors. Therefore, under nNOS inhibition by
      7-nitroindazole (7-NI) we carried out recordings of blood gasses, blood pressure
      and spontaneous EEG in conscious adult rats. Locomotion and spontaneous behavior
      were assessed in an open field. In addition skilled walking and limb coordination
      were evaluated using a ladder rung walking test. The blood gas analysis revealed
      a significant increase in pCO(2) 180 min and 240 min after the application of 7
      NI. The power and entropy decreased simultaneously with a shift of the mean
      frequency of the spontaneous EEG toward slow oscillations after 7-NI treatment.
      The thresholds of evoked potentials underwent a significant drop and a trend
      towards a slight increase in the I-O curve slope was observed. 7-NI significantly
      suppressed open field behavior expressed as distance moved, exploratory rearing
      and grooming. As for the ladder rung walking test the 7-NI treated animals had
      more errors in foot placement indicating impairment in limb coordination.
      Therefore our findings suggest that 7-NI increased cortical excitability and
      altered some physiological and behavioral parameters. 

PMID- 24908091
TI  - Immediate direct peripheral vasoconstriction in response to hyperinsulinemia and
      metformin in the anesthetized pig.
AB  - Elevated levels of insulin have been reported to induce both an arterial
      vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by
      endothelin and reactive oxygen radicals. Metformin, used to control blood glucose
      levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of
      conduit arteries. It is possible that these contradictory vascular effects are
      due to a non-direct action on arteries. Therefore, the direct effect of high
      levels of insulin and metformin infusion on resistance artery diameter was
      evaluated. Experiments were carried out on the anesthetized pig; blood flow and
      pressure were measured in the iliac artery. An adjustable snare was applied to
      the iliac above the pressure and flow measurement site to induce step decreases
      (3-4 occlusions at 5 min intervals were performed for each infusion) in blood
      flow, and hence iliac pressure, and the conductance (deltaflow / deltapressure)
      calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1
      microg/ml/min) were infused separately downstream of the adjustable snare and
      their effect on arterial conductance assessed. Insulin at both infusion rates and
      metformin caused a significant reduction in peripheral vascular conductance. In
      conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial
      vessels in vivo. 

PMID- 24908092
TI  - D-galactosamine/lipopolysaccharide-induced hepatotoxicity downregulates sirtuin 1
      in rat liver: role of sirtuin 1 modulation in hepatoprotection.
AB  - D-Galactosamine/Lipopolysaccharide (D-GalN/LPS) is a well known model of
      hepatotoxicity that closely resembles acute liver failure (ALF) seen clinically.
      The role of sirtuin 1 in this model has not yet been documented. However, there
      have been a number of studies about the cytoprotective effects of resveratrol, a
      SIRT1 activator, in the liver. This study was aimed at elucidating the roles of
      SIRT1 protein expression or catalytic activity in D-GalN/LPS model of
      hepatotoxicity. ALF was induced in male Wistar rats by intraperitoneal injection
      of D-GalN and LPS. Some groups of animals were pretreated with resveratrol and/or
      EX-527 (SIRT1 inhibitor). The effects of these treatments were evaluated by
      biochemical and Western blot studies. D-GalN/LPS treatment was able to induce
      hepatotoxicity and significantly increase all markers of liver damage and lipid
      peroxidation. A dramatic decrease of SIRT1 levels in response to D-GalN/LPS
      treatment was also documented. Resveratrol pretreatment attenuated D-GalN/LPS
      induced hepatotoxicity. EX-527 blocked the cytoprotective effects of resveratrol.
      However, both resveratrol and EX-527 pretreatments did not exhibit any
      significant effect on SIRT1 protein expression. Collectively, these results
      suggest that downregulation of SIRT1 expression is involved in the cytotoxic
      effects of D-GalN/LPS model and SIRT1 activity contributes to the cytoprotective
      effects of resveratrol in the liver. 

PMID- 24908093
TI  - Fusion and fission in the visual pathways.
AB  - Inconsistent information from different modalities can be delusive for
      perception. This phenomenon can be observed with simultaneously presented
      inconsistent numbers of brief flashes and short tones. The conflict of bimodal
      information is reflected in double flash or fission, and flash fusion illusions,
      respectively. The temporal resolution of the vision system plays a fundamental
      role in the development of these illusions. As the parallel, dorsal and ventral
      pathways have different temporal resolution we presume that these pathways play
      different roles in the illusions. We used pathway-optimized stimuli to induce the
      illusions on separately driven visual streams. Our results show that both
      pathways support the double flash illusion, while the presence of the fusion
      illusion depends on the activated pathway. The dorsal pathway, which has better
      temporal resolution, does not support fusion, while the ventral pathway which has
      worse temporal resolution shows fusion strongly. 

PMID- 24908094
TI  - Determination of homocysteine in cerebrospinal fluid as an indicator for surgery
      treatment in patients with hydrocefalus.
AB  - Increased homocysteine levels in serum are typical features of neurodegenerative
      brain diseases including hydrocephalus. The most frequent therapeutic approach
      consists of the insertion of a shunt, connecting the brain ventricles to an
      alternative drainage site. To decide whether the patient should undergo this, the
      lumbar drainage test is usually carried out to distinguish patients who can
      benefit from the shunt insertion. In searching for other potential biochemical
      markers for shunt indication we determined homocysteine levels in CSF during the
      lumbar drainage test. Homocysteine in CSF was measured during the 5-day lumbar
      drainage test in 27 patients with normal-pressure hydrocephalus (NPH) and in 25
      patients with excluded hydrocephalus. A novelized gas chromatography method with
      flame ionization detection (GC-FID) was developed and evaluated. During the first
      two days of lumbar drainage, the levels of CSF homocysteine in NPH patients were
      significantly higher compared to the controls, while on the fifth day, the
      homocysteine levels in patients with hydrocephalus reached the level of controls.
      Determination of CSF homocysteine in patients with confirmed or suspected
      hydrocephalus may serve as an independent marker for deciding on their further
      treatment strategy. 

PMID- 24908095
TI  - Changes in FGF21 serum concentrations and liver mRNA expression in an
      experimental model of complete lipodystrophy and insulin-resistant diabetes.
AB  - Patients with obesity and type 2 diabetes often display high levels of the anti
      diabetic factor fibroblast growth factor-21 (FGF21), suggesting that the
      overproduction of FGF21 may result from increased adiposity in an attempt by
      white adipose tissue (WAT) to counteract insulin resistance. However, the
      production of FGF21 diabetes in the absence of WAT has not been examined. In this
      study, we investigated the effects of lipodystrophy in A-ZIP F-1 mice on FGF21
      production in relation to diabetes. A-ZIP F-1 mice displayed high FGF21 plasma
      levels resulting from enhanced FGF21 mRNA expression in the liver. Concomitant
      enhancement of FGF21 receptor (FGFR1) and glucose transporter 1 (GLUT-1) mRNA
      expression was observed in the muscles of A-ZIP F-1 mice. Furthermore, the
      activation of hypothalamic NPY and AgRP mRNA expression positively correlated
      with plasma levels of FGF21 but not active ghrelin. Our study demonstrates that
      an increased FGF21 plasma level in lipodystrophic A-ZIP F-1 mice results mainly
      from up-regulated liver production but does not suffice to overcome the
      lipodystrophy-induced severe type 2-diabetes and insulin resistance in the liver
      linked to the augmented liver fat deposition. 

PMID- 24908097
TI  - Endoscopic ultrasonography assessment of para-esophageal varices predicts
      efficacy of propranolol in preventing recurrence of esophageal varices.
AB  - BACKGROUND: Volume of para-esophageal varices (PEV) correlates with esophageal
      varices recurrence. The effect of propranolol on volumetric change of PEV has not
      been studied. The relation between EV recurrence and volumetric change of PEV in
      patients undergoing endoscopic variceal ligation (EVL) with and without
      propranolol are studied. METHODS: Sixty-six patients who achieved EV eradication
      by primary EVL were randomly allocated to a propranolol group (n = 33) or control
      group (n = 33). The endpoints of the study were EV recurrence and volumetric
      change of PEV assessed by using endoscopic ultrasonography (EUS) at 3-month
      intervals for 2 years. RESULTS: The cumulative probability of recurrence at two
      years was 28% in the propranolol group (n = 9) and 68% in the control group (n =
      20) (p = 0.005, log-rank test). Difference of the volumetric change of PEV became
      significant as early as at the third month [-0.12 (-0.38-0.34) vs. 0.14 (-0.06
      0.57), p < 0.001] between the two groups. Regression of PEV was achieved in 20
      patients of the propranolol group at a median time of three months (range 3-12
      months), and no EV recurrence was found at the end of follow-up for two years. On
      multivariate analysis, the volumetric change of PEV at the third month and use of
      propranolol were determinants of EV recurrence. CONCLUSIONS: Propranolol may
      reduce both EV recurrence rate and volume of PEV in patients achieving endoscopic
      eradication. Regression of PEV is a predictor of durable eradication of EV
      without recurrence in patients using propranolol. EUS is an objective and useful
      tool to measure PEV and predict recurrence of EV.

PMID- 24908096
TI  - Lee Silverman voice treatment versus standard NHS speech and language therapy
      versus control in Parkinson's disease (PD COMM pilot): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Parkinson's disease is a common movement disorder affecting
      approximately 127,000 people in the UK, with an estimated two thirds having
      speech-related problems. Currently there is no preferred approach to speech and
      language therapy within the NHS and there is little evidence for the
      effectiveness of standard NHS therapy or Lee Silverman voice treatment. This
      trial aims to investigate the feasibility and acceptability of randomizing people
      with Parkinson's disease-related speech or voice problems to Lee Silverman voice
      treatment or standard speech and language therapy compared to a no-intervention
      control. METHODS/DESIGN: The PD COMM pilot is a three arm, assessor-blinded,
      randomized controlled trial. Randomization will be computer-generated with
      participants randomized at a ratio of 1:1:1. Participants randomized to
      intervention arms will be immediately referred to the appropriate speech and
      language therapist. The target population are patients with a confirmed diagnosis
      of idiopathic Parkinson's disease who have problems with their speech or voice.
      The Lee Silverman voice treatment intervention group will receive the standard
      regime of 16 sessions between 50 and 60 minutes in length over four weeks, with
      extra home practice. The standard speech and language therapy intervention group
      will receive a dose determined by patients' individual needs, but not exceeding
      eight weeks of treatment. The control group will receive standard care with no
      speech and language therapy input for at least six months post-randomization.
      Outcomes will be assessed at baseline (pre-randomization) and post- randomization
      at three, six, and 12 months. The outcome measures include patient-reported voice
      measures, quality of life, resource use, and assessor-rated speech recordings.
      The recruitment aim is at least 60 participants over 21 months from 11 sites,
      equating to at least 20 participants in each arm of the trial. This trial is
      ongoing and recruitment commenced in May 2012. DISCUSSION: This study will
      provide information on the feasibility and acceptability of randomizing
      participants to different speech and language therapies or control/deferred
      treatment. The findings relating to recruitment, treatment compliance, outcome
      measures, and effect size will inform a future phase III randomized controlled
      trial. TRIAL REGISTRATION: International Standard Randomised Controlled Trial
      Number Register: ISRCTN75223808 registered 22 March 2012.

PMID- 24908098
TI  - Evaluation of the efficacy of peritoneal lavage with distilled water in
      colorectal cancer surgery: in vitro and in vivo study.
AB  - BACKGROUND: Peritoneal lavage with distilled water has been performed during
      colorectal cancer surgery. This study investigated the cytocidal effects of
      hypotonic shock in vitro and in vivo in colorectal cancer cells. METHODS: Three
      human colorectal cancer cell lines, DLD1, HT29, and CACO2, were exposed to
      distilled water, and morphological changes were observed under a differential
      interference contrast microscope connected to a high-speed digital video camera.
      Cell volume changes were assessed using a high-resolution flow cytometer. Re
      incubation experiments were performed to investigate the cytocidal effects of
      distilled water. In the in vivo experiment, cancer cells after hypotonic shock
      were injected intraperitoneally into mice and the degree of established
      peritoneal metastasis was subsequently evaluated. The effects of the blockade of
      Cl(-) channels on these cells during hypotonic shock were also analyzed. RESULTS:
      Morphological observations revealed a rapid cell swelling followed by cell
      rupture. Measurements of cell volume changes showed that mild hypotonic shock
      induced regulatory volume decrease (RVD) while severe hypotonic shock broke cells
      into fragments. Re-incubation experiments demonstrated the cytocidal effects of
      hypotonicity. In vivo experiments revealed the absence of peritoneal
      dissemination in mice in the distilled water group, and its presence in all mice
      in the control group. The blockade of Cl(-) channels increased cell volume by
      inhibiting RVD and enhanced cytocidal effects during mild hypotonic shock.
      CONCLUSIONS: These results clearly support the efficacy of peritoneal lavage with
      distilled water during colorectal cancer surgery and suggest that regulating of
      Cl(-) transport may enhance the cytocidal effects of hypotonic shock.

PMID- 24908099
TI  - Investigating active ingredients in a complex intervention: a nested study within
      the Patient and Decision Aids (PANDAs) randomised controlled trial for people
      with type 2 diabetes.
AB  - BACKGROUND: Randomised trials provide evidence that patient decision aids improve
      outcomes with respect to patient knowledge, involvement and satisfaction in
      decision making. It is less clear how these complex interventions are implemented
      within patient-clinician interactions and which components are active for
      improving decision processes. To investigate the experiences of using a diabetes
      treatment decision aid and to explore how components within a complex
      intervention influenced the decision making process. METHODS: A pragmatic mixed
      methods study nested within the PANDAs cluster randomised trial of a patient
      decision aid. Themes inductively derived from interviews and observation of
      consultations with further triangulation with results of decision quality and
      involvement measurements and case analyses. RESULTS: The decision aid
      intervention was employed flexibly within the consultation with both the patient
      and clinician active in marshalling elements. The decision aid improved
      processing and organization of information needed for decision making within the
      consultation interaction. It also improved decision quality by preparing the
      patient for active involvement within the clinical consultation. CONCLUSION: The
      intervention was acceptable, flexible and readily implemented in primary care
      consultations. The decision aid was effective in facilitating cognitive
      processing. The intervention also facilitated rehearsal in preparation for active
      roles in a shared decision process. TRIAL REGISTRATION: Trials Register Number:
      ISRCTN14842077. Date registered: 24.06.2010.

PMID- 24908100
TI  - Targeting cells with single vectors using multiple-feature Boolean logic.
AB  - Precisely defining the roles of specific cell types is an intriguing frontier in
      the study of intact biological systems and has stimulated the rapid development
      of genetically encoded tools for observation and control. However, targeting
      these tools with adequate specificity remains challenging: most cell types are
      best defined by the intersection of two or more features such as active promoter
      elements, location and connectivity. Here we have combined engineered introns
      with specific recombinases to achieve expression of genetically encoded tools
      that is conditional upon multiple cell-type features, using Boolean logical
      operations all governed by a single versatile vector. We used this approach to
      target intersectionally specified populations of inhibitory interneurons in
      mammalian hippocampus and neurons of the ventral tegmental area defined by both
      genetic and wiring properties. This flexible and modular approach may expand the
      application of genetically encoded interventional and observational tools for
      intact-systems biology. 

PMID- 24908101
TI  - Melanocortin 4 receptors in autonomic neurons regulate thermogenesis and
      glycemia.
AB  - Whether melanocortin 4 receptors (MC4Rs) in extra-hypothalamic neurons, including
      cholinergic autonomic pre-ganglionic neurons, are required to control energy and
      glucose homeostasis is unclear. We found that MC4Rs in sympathetic, but not
      parasympathetic, pre-ganglionic neurons were required to regulate energy
      expenditure and body weight, including thermogenic responses to diet and cold
      exposure and 'beiging' of white adipose tissue. Deletion of Mc4r genes in both
      sympathetic and parasympathetic cholinergic neurons impaired glucose homeostasis.

PMID- 24908102
TI  - Behavioral and neurophysiological correlates of regret in rat decision-making on
      a neuroeconomic task.
AB  - Disappointment entails the recognition that one did not get the value expected.
      In contrast, regret entails recognition that an alternative (counterfactual)
      action would have produced a more valued outcome. In humans, the orbitofrontal
      cortex is active during expressions of regret, and humans with damage to the
      orbitofrontal cortex do not express regret. In rats and nonhuman primates, both
      the orbitofrontal cortex and the ventral striatum have been implicated in reward
      computations. We recorded neural ensembles from orbitofrontal cortex and ventral
      striatum in rats encountering wait or skip choices for delayed delivery of
      different flavors using an economic framework. Economically, encountering a high
      cost choice after skipping a low-cost choice should induce regret. In these
      situations, rats looked backwards toward the lost option, cells within
      orbitofrontal cortex and ventral striatum represented the missed action, rats
      were more likely to wait for the long delay, and rats rushed through eating the
      food after that delay. 

PMID- 24908104
TI  - Factors affecting food handling practices among food handlers of Dangila town
      food and drink establishments, North West Ethiopia.
AB  - BACKGROUND: Food borne diseases are major health problems in developed and
      developing countries including Ethiopia. The problem is more noticeable in
      developing countries due to prevailing poor food handling and sanitation
      practices, inadequate food safety laws, weak regulatory systems, lack of
      financial resources to invest on safer equipments, and lack of education for food
      handlers. METHODS: The objective of this study was to assess food handling
      practice and associated factors among food handlers working in food and drinking
      establishments of Dangila town, North West Ethiopia. Cross-sectional quantitative
      study design was conducted among 406 food handlers working in 105 food and drink
      establishments from July to August 2013 in Dangila town. Data were collected
      using face to face interview with pretested structured questionnaire and physical
      observation. RESULT: The mean age of the respondents was 22.7 +/- 4.2 years of
      which 62.8% of the food handlers were females. Two hundred thirteen (52.5%) of
      food handlers had good food handling practices. Marital status (AOR = 7.52, 95%
      CI, 1.45-38.97), monthly income (AOR = 0.395, 95% CI, 0.25-0.62), knowledge about
      food handling (AOR = 1.69, 95% CI, 1.05-2.73), existence of shower facility (AOR
      = 1.89, 95% CI, 1.12-3.21) and separate dressing room (AOR = 1.97, 95% CI, 1.11
      3.49) were found to be significantly associated with good food handling
      Practices. CONCLUSION: Above half of food handlers had good food handling
      practices. Marital status, monthly income, knowledge status, existence of shower
      facility, existence of separate dressing room and presence of insect and rodent
      were factors associated with food handling Practices.

PMID- 24908105
TI  - The role of the Australian workplace return to work coordinator: essential
      qualities and attributes.
AB  - INTRODUCTION: In the Australian context, a return to work (RTW) Coordinator
      assists an injured worker with workplace-based support and regulatory guidance
      for the duration of their injury. Coordinating the RTW process has been
      considered an effective approach for managing workplace injuries, however few
      studies have described the skills, traits or characteristics required to fulfil
      the role of workplace RTW Coordinator. This study aims to provide insight as to
      the skills and attributes needed for the role of the workplace RTW Coordinator
      from their experience and perception. METHOD: Focus groups were conducted with
      workplace RTW Coordinators from six major Australian cities. Twenty five
      participants were recruited through a national RTW Coordinator website, and
      professional RTW interest groups using a snowballing technique. Participating
      workplace RTW Coordinators were required to have a minimum 2 years' experience
      and to have been involved with the development and implementation of workplace
      policies and procedures. Thematic analysis was performed to identify meaningful
      patterns and themes. RESULTS: The data analysed provided clear insight as to the
      specific role requirements necessary for working as an Australian workplace RTW
      Coordinator. Three key themes clearly emerged; communication skills, RTW
      Coordinator characteristics, and managing the RTW process. CONCLUSION: The
      findings indicate that RTW Coordinators require a wide range of traits, skills,
      and attributes to successfully perform this role. Effective management by the RTW
      Coordinator of the complex RTW process is essential to facilitate a smooth
      transition for the injured worker, alongside maintaining a professional
      relationship with the employer and external stakeholders. The results of this
      study can be utilised to further improve the selection of future RTW
      Coordinators.

PMID- 24908103
TI  - A spike-timing mechanism for action selection.
AB  - We discovered a bimodal behavior in the genetically tractable organism Drosophila
      melanogaster that allowed us to directly probe the neural mechanisms of an action
      selection process. When confronted by a predator-mimicking looming stimulus, a
      fly responds with either a long-duration escape behavior sequence that initiates
      stable flight or a distinct, short-duration sequence that sacrifices flight
      stability for speed. Intracellular recording of the descending giant fiber (GF)
      interneuron during head-fixed escape revealed that GF spike timing relative to
      parallel circuits for escape actions determined which of the two behavioral
      responses was elicited. The process was well described by a simple model in which
      the GF circuit has a higher activation threshold than the parallel circuits, but
      can override ongoing behavior to force a short takeoff. Our findings suggest a
      neural mechanism for action selection in which relative activation timing of
      parallel circuits creates the appropriate motor output. 

PMID- 24908106
TI  - New-onset hyponatraemia after surgery for traumatic hip fracture.
AB  - BACKGROUND: hyponatraemia in orthopaedic patients is common but has been poorly
      investigated following surgery for traumatic hip fracture. The aims of this study
      were to define the incidence of new-onset post-operative hyponatraemia and to
      investigate associations between hyponatraemia and patient demographics,
      medication use and duration of hospital stay. METHODS: all patients admitted to
      the Orthopaedic Unit for hip surgery following trauma in 2012 were
      retrospectively reviewed. Patients who developed post-operative hyponatraemia
      within 10 days of surgery were compared with patients who remained normonatraemic
      pre- and post-operatively. RESULTS: a total of 254 patients were included.
      Overall, this study identified a significant (P =< 0.001) mean post-operative
      drop in serum sodium of 1.8 mmol/l (95% CI: 1.3-2.3%) compared with pre-operative
      levels. The incidence of moderate (<135 mmol/l) and severe (<130 mmol/l) post
      operative hyponatraemia was 27% (95% CI: 21.7-32.5%) and 9% (95% CI: 5.7-12.8%),
      respectively. Statistical analysis revealed significant associations between the
      development of post-operative hyponatraemia and: (i) proton pump inhibitor use,
      (ii) selective serotonin re-uptake inhibitor use and (iii) increasing number of
      medications. Length of hospital stay was significantly increased in patients with
      moderate post-operative hyponatraemia compared with normonatraemic patients (30
      versus 21 days; P =< 0.001). The incidence of new-onset post-operative
      hyponatraemia was not significantly increased by ethnicity, gender, fracture
      type, functional status or operative procedure. CONCLUSION: hyponatraemia after
      surgery for hip fracture is common and results in longer hospital stay. This
      study provides evidence that an average post-operative drop in serum sodium
      concentration should be expected in this patient group. Moreover, patients taking
      SSRI or PPI medications may be at increased risk of post-operative hyponatraemia.

PMID- 24908107
TI  - Renal function and decline in functional capacity in older adults.
AB  - BACKGROUND: longitudinal relationship between renal function, disability and
      mortality has not been evaluated. OBJECTIVE: we investigated the temporal
      association between renal function and disability, and aimed to identify the
      influence of disability on mortality according to renal function in a cohort of
      older Koreans. DESIGN/SETTING: Korean Longitudinal Study on Health and Aging is a
      prospective, population-based cohort. SUBJECTS: community-dwelling Koreans >=65
      years of age. MAIN OUTCOME MEASURES: Korean version of activities of daily living
      (ADL), Instrumental activities of daily living (IADL) and all-cause mortality.
      RESULTS: a total of 984 participants were followed for 5 years with a 70.9%
      participation rate. The participants were categorized into three groups according
      to their baseline estimated glomerular filtration rates (eGFRs) (Group I, >=60;
      Group II, 45-59; and Group III, <45 ml/min/1.73 m(2)). Baseline eGFR was higher
      in participants who maintained functional status compared with participants who
      died or had disability at follow-up examination. The incidence of ADL/IADL
      decline was 13, 12.5 and 29.5% in participants who showed improvement, no change,
      and decline in renal function, respectively (P = 0.01). The hazard ratio for
      mortality in the subgroup with IADL disability was 1.87 (95% CI: 1.10-3.20, P =
      0.022) in Group I, and 2.53 (95% CI: 1.57-4.09, P<0.001) in Groups II and III
      after adjustment. CONCLUSIONS: impaired renal function was related to disability
      and ADL/IADL decline. The effect of ADL/IADL disability on mortality was more
      prominent in participants with impaired eGFR.

PMID- 24908108
TI  - The effects of cardiac output and pulmonary arterial hypertension on volumetric
      capnography derived-variables during normoxia and hypoxia.
AB  - The aim of this study was to test the effect of cardiac output (CO) and pulmonary
      artery hypertension (PHT) on volumetric capnography (VCap) derived-variables.
      Nine pigs were mechanically ventilated using fixed ventilatory settings. Two
      steps of PHT were induced by IV infusion of a thromboxane analogue: PHT25 [mean
      pulmonary arterial pressure (MPAP) of 25 mmHg] and PHT40 (MPAP of 40 mmHg). CO
      was increased by 50% from baseline (COup) with an infusion of dobutamine>=5 MUg
      kg(-1) min(-1) and decreased by 40% from baseline (COdown) infusing sodium
      nitroglycerine>=30 MUg kg(-1) min(-1) plus esmolol 500 MUg kg(-1) min(-1).
      Another state of PHT and COdown was induced by severe hypoxemia (FiO2 0.07).
      Invasive hemodynamic data and VCap were recorded and compared before and after
      each step using a mixed random effects model. Compared to baseline, the
      normalized slope of phase III (SnIII) increased by 32% in PHT25 and by 22% in
      PHT40. SnIII decreased non-significantly by 4% with COdown. A combination of PHT
      and COdown associated with severe hypoxemia increased SnIII by 28% compared to
      baseline. The elimination of CO2 per breath decreased by 7% in PHT40 and by 12%
      in COdown but increased only slightly with COup. Dead space variables did not
      change significantly along the protocol. At constant ventilation and body
      metabolism, pulmonary artery hypertension and decreases in CO had the biggest
      effects on the SnIII of the volumetric capnogram and on the elimination of CO2.

PMID- 24908109
TI  - A systems biology investigation of neurodegenerative dementia reveals a pivotal
      role of autophagy.
AB  - BACKGROUND: Neurodegenerative dementia comprises chronic and progressive
      illnesses with major clinical features represented by progressive and permanent
      loss of cognitive and mental performance, including impairment of memory and
      brain functions. Many different forms of neurodegenerative dementia exist, but
      they are all characterized by death of specific subpopulation of neurons and
      accumulation of proteins in the brain. We incorporated data from OMIM and primary
      molecular targets of drugs in the different phases of the drug discovery process
      to try to reveal possible hidden mechanism in neurodegenerative dementia. In the
      present study, a systems biology approach was used to investigate the molecular
      connections among seemingly distinct complex diseases with the shared clinical
      symptoms of dementia that could suggest related disease mechanisms. RESULTS:
      Network analysis was applied to characterize an interaction network of disease
      proteins and drug targets, revealing a major role of metabolism and,
      predominantly, of autophagy process in dementia and, particularly, in
      tauopathies. Different phases of the autophagy molecular pathway appear to be
      implicated in the individual disease pathophysiology and specific drug targets
      associated to autophagy modulation could be considered for pharmacological
      intervention. In particular, in view of their centrality and of the direct
      association to autophagy proteins in the network, PP2A subunits could be
      suggested as a suitable molecular target for the development of novel drugs.
      CONCLUSION: The present systems biology investigation identifies the autophagy
      pathway as a central dis-regulated process in neurodegenerative dementia with a
      prevalent involvement in diseases characterized by tau inclusion and indicates
      the disease-specific molecules in the pathway that could be considered for
      therapy.

PMID- 24908110
TI  - Effects of selenium-enriched Agaricus blazei Murill on liver metabolic
      dysfunction in mice, a comparison with selenium-deficient Agaricus blazei Murill
      and sodium selenite.
AB  - In the present study, we investigated the effects of Se-enriched Agaricus blazei
      Murill (Se-AbM) on liver injury in mice induced by acute alcohol administration.
      Mice received ethanol (5 g/kg body weight (BW)) by gavage every 12 h for a total
      of 3 doses. Se-AbM was administrated before ethanol administration. Subsequent
      serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST)
      level, maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS),
      nuclear factor kappa B (NF-kappaB) level, polymorphonuclear cells (PMN) level,
      interleukin-1beta (IL-1beta) level, inducible nitric oxide synthase (iNOS) level,
      tumor necrosis factor-alpha (TNF-alpha) level, intercellular adhesion molecule 1
      (ICAM-1), and cyclooxygenase-2 (COX-2) were determined by ELISA and
      immunohistochemistry, respectively. Se-AbM administration markedly (p < 005)
      decreased serum ALT, AST, and MDA levels, hepatic IL-1beta and TNF-alpha levels,
      as well as PMN infiltration and the expression of ICAM-1, COX-2, iNOS, and NF
      kappaB compared with alcohol administration. In conclusion, we observed that Se
      AbM supplementation could restrain the hepatic damage caused by acute alcohol
      exposure.

PMID- 24908111
TI  - Low serum levels of zinc, copper, and iron as risk factors for osteoporosis: a
      meta-analysis.
AB  - Zinc (Zn), copper (Cu), and iron (Fe) are essential trace elements for the
      growth, development, and maintenance of healthy bones. However, there are
      conflicting reports as to the relationship between serum level of Zn, Cu, or Fe
      and osteoporosis (OP). The purpose of the present study is to clarify the
      relationship between serum Zn, Cu, or Fe and OP using a meta-analysis approach.
      We searched all articles indexed in PubMed published up to May 2014 concerning
      the association between serum level of Zn, Cu, or Fe and OP. Eight eligible
      articles involving 2,188 subjects were identified. Overall, pooled analysis
      indicated that patients with OP had a lower serum level of Zn, Cu, or Fe than the
      healthy controls (Zn standardized mean difference (SMD) = -1.396, 95% confidence
      interval (CI) = [-2.129, -0.663]; Cu SMD = -0.386, 95% CI = [-0.538, -0.234]; Fe
      SMD = -0.22, 95% CI = [-0.30, -0.13]). Further subgroup analysis found that
      geographical location and gender had an influence on the serum level of Zn in OP
      and healthy controls, but not on the serum level of Cu or Fe. No evidence of
      publication bias was observed. In conclusion, this meta-analysis suggests that
      low serum levels of Zn, Cu, and Fe seem to be important risk factors for OP and
      well-designed studies with adequate control for confounding factors are required
      in future investigations.

PMID- 24908113
TI  - Interactions between fungal growth, substrate utilization, and enzyme production
      during solid substrate cultivation of Phanerochaete chrysosporium on cotton
      stalks.
AB  - Fungal pretreatment, using lignin-degrading microorganisms to improve
      lignocellulosic feedstocks with minimal energy input, is a potential alternative
      to physiochemical pretreatment methods. Identifying the kinetics for fungal
      pretreatment during solid substrate cultivation is needed to help establish the
      processing conditions for effective scale up of this technology. In this study, a
      set of mathematical models were proposed for describing the interactions between
      holocellulose consumption, lignin degradation, cellulase, ligninolytic enzyme,
      and the growth of Phanerochaete chrysosporium during a 14 day fungal pretreatment
      process. Model parameters were estimated and validated by the System Biology
      Toolbox in MatLab. Developed models provided sufficiently accurate predictions
      for fungal growth (R (2) = 0.97), holocellulose consumption (R (2) = 0.97),
      lignin degradation (R (2) = 0.93) and ligninolytic enzyme production (R (2) =
      0.92), and fair prediction for cellulase production (R (2) = 0.61). The models
      provide valuable information for understanding the interactive mechanisms in
      biological systems as well as for fungal pretreatment process scale up and
      improvement. 

PMID- 24908112
TI  - Protective effect of p-methoxycinnamic acid, an active phenolic acid against 1,2
      dimethylhydrazine-induced colon carcinogenesis: modulating biotransforming
      bacterial enzymes and xenobiotic metabolizing enzymes.
AB  - Objective of the study is to evaluate the modifying potential of p
      methoxycinnamic acid (p-MCA), an active rice bran phenolic acid on
      biotransforming bacterial enzymes and xenobiotic metabolizing enzymes in 1,2
      dimethylhydrazine-induced rat colon carcinogenesis. 48 male albino wistar rats
      were divided into six groups. Group1 (control) received modified pellet diet and
      0.1 % carboxymethylcellulose; group2 received modified pellet diet along with p
      MCA (80 mg/kg b.wt. p.o.) everyday for 16 weeks; groups 3-6 received 1,2
      dimethylhydrazine (DMH) (20 mg/kg b.wt.) subcutaneous injection once a week for
      the first 4 weeks, while groups 4-6 received p-MCA at three different doses of
      20, 40 and 80 mg/kg b.wt. p.o. everyday for 16 weeks. A significant increase in
      carcinogen-activating enzymes (cytochrome P450, cytochrome b5, cytochrome
      P4502E1, NADH-cytochrome-b5-reductase and NADPH-cytochrome-P450 reductase) with
      concomitant decrease in phaseII enzymes, DT-Diaphorase, glutathione S
      transferase, UDP-glucuronyl-transferase and gamma glutamyltransferase were
      observed in group3 compared to control. DMH treatment significantly increased the
      activities of feacal and colonic bacterial enzymes (beta-glucosidase, beta
      galactosidase, beta-glucuronidase, nitroreductase, sulphatase and mucinase). p
      MCA supplementation (40 mg/kg b.wt) to carcinogen exposed rats inhibited these
      enzymes, which were near those of control rats. The formation of dysplastic
      aberrant crypt foci in the colon and the histopathological observations of the
      liver also supports our biochemical findings. p-MCA (40 mg/kg b.wt.) offers
      remarkable modulating efficacy of biotransforming bacterial and xenobiotic
      metabolizing enzymes in colon carcinogenesis.

PMID- 24908115
TI  - Transient expression in Arabidopsis leaf mesophyll protoplast system for cell
      based functional analysis of MAPK cascades signaling.
AB  - Mitogen-Activated Protein Kinase (MAPK) cascade is one of the main signaling
      components mediating abiotic and biotic stress and hormone information in plants.
      Plant MAPK study has been impeded with a genetic approach using a long-term
      phenotypic analysis in spite of the transient nature of the protein kinase
      signaling. Arabidopsis leaf mesophyll protoplasts provide a versatile resource
      for diverse cell-based assays to acquire immediate molecular and biochemical
      responses with transient expression of MAPK cascade components of interests.
      Thus, it is an attractive tool for a high-throughput functional analysis of
      Arabidopsis MAPK cascade signaling. However, transient expression in Arabidopsis
      mesophyll protoplast (TEAMP) system requires mastered skills for protoplast
      preparation and handling to achieve steady and stable data. Here, we have
      described two analytical methods for MAPK cascade signaling using TEAMP system. 

PMID- 24908116
TI  - Quantification of stress-induced mitogen-activated protein kinase expressional
      dynamic using reverse transcription quantitative real-time PCR.
AB  - Although it is generally accepted that signal transduction in plant mitogen
      activated protein kinase signaling cascades is regulated via rapid
      posttranslational modifications, there are also several compelling examples of
      swift stress induced transcriptional activation of plant MAP kinase genes. A
      possible function of these fast and transient events is to compensate for protein
      losses caused by degradation of phosphorylated MAP kinases within stimulated
      pathways. Nevertheless, there is still need for additional evidence to precisely
      describe the regulatory role of plant MAP kinase transcriptional dynamics,
      especially in the context of whole stress stimulated pathways including also
      other signaling molecules and transcription factors. During the last two decades
      a reverse transcription quantitative real-time PCR became a golden choice for the
      accurate and fast quantification of the gene expression and gene expression
      dynamic. In here, we provide a robust, cost-effective SYBR Green-based RT-qPCR
      protocol that is suitable for the quantification of stress induced plant MAP
      kinase transcriptional dynamics in various plant species.

PMID- 24908117
TI  - Analysis of MAPK activities using MAPK-specific antibodies.
AB  - Phosphorylation of proteins by mitogen-activated protein kinases is central to
      many cellular processes, including signal transduction after stress encounter.
      Thus, assays to identify or characterize MAP kinase activities are a key tool for
      research in this area. While in-gel kinase assays using isotope-labeled ATP are a
      powerful tool to investigate the general induction of MAPK activities in any
      organism, alternative methods using phospho-specific MAPK antibodies are now
      being established for many model organisms. However, both in-gel kinase assay and
      phospho-specific western blot analysis do not allow for the unambiguous
      identification of the activated MAPK. To obtain specificity, initial
      immunoprecipitation purification of the kinase of interest prior to further
      analysis can be performed. 

PMID- 24908114
TI  - Overexpression of Ephrin A2 receptors in cancer stromal cells is a prognostic
      factor for the relapse of gastric cancer.
AB  - BACKGROUND: Microenvironments control cancer growth and progression. We explored
      the prognostic impact of stromal reaction and cancer stromal cells on relapse
      risk and survival after curative gastrectomy in gastric cancer patients. METHODS:
      Tissue samples were obtained from 107 patients with gastric adenocarcinoma who
      underwent curative (R0) gastrectomy. Primary stromal cells isolated from gastric
      cancer tissue (GCSC) and normal gastric tissue (Gastric stromal cell: GSC) in
      each patient were cultured and subjected to comprehensive proteome (LC-MS/MS) and
      real-time RT-PCR analysis. Expression of Ephrin A2 receptors (EphA2) in cancers
      and GCSC was evaluated immunohistochemically. Intermingling of EphA2-positive
      cancer cells and GCSC (IC/A2+) and overexpression of EphA2 in cancer cells
      (Ca/A2+) in invasive parts of tumors were assessed, as were relationships of
      IC/A2+, Ca/A2+, and clinicopathological factors with relapse-free survival and
      overall survival. RESULTS: Proteome analysis showed that EphA2 expression was
      significantly higher in GCSC than GSC. Real-time RT-PCR analysis showed that
      levels of EphA1/A2/A3/A5 and EphB2/B4 were >=2.0-fold higher in GCSC than GSC.
      Ca/A2 and IC/A2 were positive in 65 (60.7 %) and 26 (24.3 %) patients,
      respectively. Relapse was significantly more frequent in IC/A2-positive than in
      IC/A2-negative (HR, 2.12; 95 % CI, 1.16-5.41; p = 0.0207) patients. Among the 54
      patients who received S-1 adjuvant chemotherapy, relapse-free survival (RFS) was
      significantly shorter in those who were IC/A2-positive than in those who were
      IC/A2-negative and Ca/A2-negative (HR, 2.83; 95 % CI, 1.12-12.12; p = 0.0339).
      Multivariable analysis indicated that pathological stage (p = 0.010) and IC/A2+
      (p = 0.008) were independent risk factors for recurrence. CONCLUSION: IC/A2+ was
      predictive of relapse after curative (R0) gastrectomy.

PMID- 24908118
TI  - Detection of protein phosphorylation and charge isoforms using vertical one
      dimensional isoelectric focusing gels.
AB  - During many biological responses, changes in protein modifications (e.g.,
      phosphorylation) are often more critical than changes in protein abundance in
      determining the outcome of cellular responses. These important regulatory changes
      can alter a protein's location, activity, or binding partners. Monitoring
      modifications such as phosphorylation is often impeded, or even prevented,
      because of the need for specialized reagents and equipment that are expensive
      and/or time-consuming to produce. However, many protein modifications alter the
      isoelectric point (pI) of a protein. Therefore, we developed a denaturing, one
      dimensional isoelectric focusing (IEF) procedure that separates proteins based on
      their pI to resolve different isoforms, allowing a relatively simple strategy for
      detecting changes in protein modifications. Although similar results can be
      achieved by two-dimensional gel electrophoresis, the method described here uses a
      multi-well SDS-PAGE format that allows many more samples to be assayed within a
      single gel, thereby greatly decreasing both the time and cost needed to assess
      modifications of a single protein in response many different treatment
      conditions. To increase the sensitivity of detection, we also optimized a
      procedure to transfer proteins from these gels to membranes for subsequent
      immunodetection. This combination of techniques provides the means of
      interrogating the number and stoichiometry of isoforms from total protein
      extracts without a priori knowledge of which modification may occur. 

PMID- 24908119
TI  - Affinity-based SDS PAGE identification of phosphorylated Arabidopsis MAPKs and
      substrates by acrylamide pendant Phos-TagTM.
AB  - Protein phosphorylation is the most abundant and best studied protein
      posttranslational modification, dedicated to the regulation of protein function
      and subcellular localization as well as to protein-protein interactions.
      Identification and quantitation of the dynamic, conditional protein
      phosphorylation can be achieved by either metabolic labeling of the protein of
      interest with (32)P-labeled ATP followed by autoradiographic analysis, the use of
      specific monoclonal or polyclonal antibodies against the phosphorylated protein
      species and finally by phosphoproteome delineation using mass spectrometry.Hereby
      we present a fourth alternative which relies on the enforced-affinity-based
      electrophoretic separation of phosphorylated from non-phosphorylated protein
      species by standard SDS-PAGE systems co-polymerized with Phos-TagTM and Mn(2+) or
      Zn(2+) cations. Phosphate groups of phosphorylated Ser, Thr, and Tyr residues
      form complexes with Mn(2+) and Zn(2+) cations with polyacrylamide immobilized
      Phos-TagTM. Following appropriate treatment of the gels, separated proteins can
      be quantitatively transferred to PVDF or nitrocellulose membranes and probed with
      common-not phosphorylation state specific-antibodies and delineate the occurrence
      of a certain phosphoprotein species against its non-phosphorylated counterpart.

PMID- 24908120
TI  - Identification of constitutively active AtMPK6 mutants using a functional screen
      in Saccharomyces cerevisiae.
AB  - MAPK (Mitogen-Activated Protein Kinases) mutants which are active independently
      of phosphorylation by upstream MAPK Kinases (MAPKKs) help to clarify signal
      transduction processes through MAPK modules and provide a useful tool to
      understand MAPK roles in the cell. The identification of such mutations is
      tricky. In this chapter, we provide a detailed protocol for their screening,
      taking advantage of a functional expression assay in yeast. 

PMID- 24908121
TI  - Virus-induced gene silencing in plant MAPK research.
AB  - Virus-induced gene silencing (VIGS) technology has become more and more widely
      used in various plant species for rapid screening of gene functions. VIGS does
      not require time-consuming tissue culture steps that are needed for stable
      transformation in most plant species and it can be used for studying gene
      function even in plants that are very difficult to stably transform. Furthermore,
      VIGS technology provides high gene silencing efficiency (up to 95 %) and
      specificity. Here, we describe a VIGS protocol that can be used for studying the
      functions of MAPKs and other genes in a wild tobacco species, Nicotiana
      attenuata. This method is also suitable for other Nicotiana species and tomato
      with minor modifications.

PMID- 24908122
TI  - RNA interference of plant MAPK cascades for functional studies.
AB  - Arabidopsis genome contains 20 genes encoding mitogen-activated protein kinases
      (MAPKs, or MPKs), and ten genes encoding MAPK kinases (MAPKKs, or MKKs), the
      upstream kinases that activate MAPKs in the signaling cascades. They play
      critical roles in many different biological processes ranging from
      growth/development to response to environmental stimuli and pathogen invasion. T
      DNA knockout lines are not currently available for all these genes. There is also
      functional redundancy at both MAPK and MAPKK levels. In addition, embryo
      lethality is associated with some double mutant combinations, which makes it
      difficult to investigate their specific functions in plants. In such situation,
      the use of RNA interference technology by which mRNA of interested gene is
      targeted by double-stranded RNA (dsRNA) for degradation and gene silencing
      provides a powerful tool for loss-of-function analyses. In this chapter, we
      describe the hairpin-RNA interference (hpRNAi) method we employed to silence
      MPK3/MPK6 and their upstream MKK4/MKK5 in the model plant Arabidopsis, with
      particular emphasis on the generation of hpRNAi constructs for single gene RNAi,
      tandem RNAi of two MAPKK genes, and tissue-specific RNAi.

PMID- 24908123
TI  - Immunofluorescent localization of MAPKs and colocalization with microtubules in
      Arabidopsis seedling whole-mount probes.
AB  - In all eukaryotes, signaling by mitogen-activated protein kinase (MAPK) pathways
      plays a crucial role in signal transduction during regulation of cell growth,
      differentiation, proliferation as well as death and stress responses. In this
      chapter we describe a reliable method to immunolocalize MAPKs in roots of
      Arabidopsis thaliana by using whole-mount seedling probes. This method relies on
      quick and efficient chemical fixation, partial cell wall digestion, plasma
      membrane permeabilization, subsequent antibody incubation, and visualization by
      high-end confocal laser scanning microscopy (CLSM) performed on whole Arabidopsis
      seedlings. Protocols are provided for immunofluorescent localization of MPK3,
      MPK4, and MPK6, representing three major developmentally and stress-regulated
      MAPKs of Arabidopsis. In addition, protocols for colocalization of these MAPKs
      with microtubules are also provided.

PMID- 24908124
TI  - Immunofluorescent localization of MAPKs in Steedman's wax sections.
AB  - Signals of different nature are transduced in cells through signal transduction
      pathways, where mitogen-activated protein kinases (MAPKs) play an important role
      as signaling molecules. Views into intracellular localization of MAPKs are
      critical for the understanding of their spatial and temporal functions, like
      activation-based relocation, compartmentation, or interactions with local
      substrates. Localization of MAPKs in cells is thus very useful cell biological
      approach, extending complex mode of cell signaling characterization in plants.
      Here, we present a method for subcellular immunofluorescence localization of
      MAPKs using protein- or phospho-specific antibodies, performed on sectioned fixed
      plant samples. It is based on embedding of samples in the Steedman's wax, a low
      melting point polyester wax embedding medium, which maintains high antigenicity
      of studied proteins. In addition, exposure of dewaxed sections to antibodies
      allows for their efficient penetration. Altogether, it makes this simple method a
      good tool in the efficient subcellular localization of diverse proteins,
      including plant MAPKs.

PMID- 24908125
TI  - Fluorescent protein tagging of Arabidopsis MAPKs for in vivo localization
      studies.
AB  - Mitogen-activated protein kinases (MAPK) are key regulatory elements in many
      processes. They are highly conserved throughout eukaryotes. In plants, MAPKs are
      involved in biotic and abiotic stress responses; they regulate cell division,
      cell growth, and also programmed cell death. In vivo visualization of MAPKs is
      crucial for understanding of their spatiotemporal organization. Cloning of MAPK
      fluorescent protein fusions might present difficulties related to the
      preservation of protein-protein interactions essential for MAPK localization,
      interactions with upstream and downstream regulators, and finally substrate
      targeting. In this chapter we describe cloning of MAPKs in the flexible MultiSite
      Gateway((r)) cloning system followed by easy and quick testing of binary vectors
      by transient assays in Arabidopsis thaliana and Nicotiana benthamiana.

PMID- 24908126
TI  - Bimolecular fluorescent complementation (BiFC) by MAP kinases and MAPK
      phosphatases.
AB  - The adaptation of plants to the environment is a key property for survival.
      Adaptation responses to environmental cues are generated in cells by signaling
      initiated from cell receptors. Signal transduction is based on protein
      phosphorylation that is employed in mitogen-activated protein kinase (MAPK)
      cascades to integrate signals from receptors to cellular responses. MAPK activity
      is determined by phosphorylation of amino acid residues within the kinase
      activation loop and their dephosphorylation by phosphatases is essential to
      control signal duration and intensity.Monitoring protein-protein interactions
      (PPIs) of MAPKs with MAPK phosphatases in vivo provides valuable information
      about specificity and intracellular localization of the protein complex. Here, we
      report studying PPIs between Arabidopsis MAPKs and PP2C-type MAPK phosphatases
      using bimolecular fluorescent complementation (BiFC) in suspension cell
      protoplasts. The interactions of the MAPKs MPK3, MKP4 and MPK6 with the
      phosphatases AP2C1 and AP2C3 have been tested.

PMID- 24908127
TI  - Determination of phosphorylation sites in microtubule associated protein MAP65-1.
AB  - Reorganization of microtubules during cell cycle depends on the modulation of
      activity of microtubule-associated proteins. MAP65 is one of the main microtubule
      structural proteins in plants responsible for the formation of bundles of
      parallel and antiparallel microtubules. A member of MAP65 protein family, MAP65
      1, binds to microtubules of preprophase band during early stages of cell division
      and later to the midzone of anaphase spindle and the phragmoplast, but exhibits
      no or reduced microtubule binding during metaphase. Artificially induced
      interaction of MAP65-1 with microtubules during metaphase promotes excessive
      formation of pole-to-pole microtubule bundles and causes delay of anaphase onset.
      The exact mechanism of this delay is not known, but it was suggested that
      microtubule bundles induced by MAP65 impose spatial constraints on the chromosome
      movement obstructing their alignment in the metaphase plate. Interaction of MAP65
      1 with microtubules is controlled by phosphorylation. This chapter describes a
      strategy for the identification of phosphorylation residues responsible for the
      cell-cycle control of MAP65-1 activity.

PMID- 24908128
TI  - In vivo phosphorylation of WRKY transcription factor by MAPK.
AB  - Plants activate signaling networks in response to diverse pathogen-derived
      signals, facilitating transcriptional reprogramming through mitogen-activated
      protein kinase (MAPK) cascades. Identification of phosphorylation targets of MAPK
      and in vivo detection of the phosphorylated substrates are important processes to
      elucidate the signaling pathway in plant immune responses. We have identified a
      WRKY transcription factor, which is phosphorylated by defense-related MAPKs, SIPK
      and WIPK. Recent evidence demonstrated that some group I WRKY transcription
      factors, which contain a conserved motif in the N-terminal region, are activated
      by MAPK-dependent phosphorylation. In this chapter, we describe protocols for
      preparation of anti-phosphopeptide antibodies, detection of activated MAPKs using
      anti-phospho-MAPK antibody, and activated WRKY using anti-phospho-WRKY antibody,
      respectively.

PMID- 24908129
TI  - Rapid mutagenesis-based analysis of phosphorylation sites in mitogen-activated
      protein kinase substrates.
AB  - In eukaryotes, mitogen-activated protein kinases (MAPKs) are one of the best
      studied pathways for posttranslational modification-mediated regulation of
      protein functions. Here, we describe a rapid in vitro method to screen potential
      protein phosphorylation sites targeted by MAPKs. The method is based on PCR
      mediated mutagenesis together with a type IIs restriction digest. Screening for
      the successfully mutated clones is further facilitated through introduction of a
      second diagnostic restriction site. Besides time-saving, this reduces the cost
      for sequencing confirmation of the positive clones, which are used for subsequent
      recombinant protein production and kinase assay validation. 

PMID- 24908130
TI  - Yeast two-hybrid system for dissecting the rice MAPK interactome.
AB  - Protein-protein interactions are a preliminary but fundamental key to many
      biological systems. Identification of proteins that interact with particular bait
      not only contributes to a deeper understanding of bait protein function but also
      provides much information for the discovery of larger-scale interaction networks
      (interactome). Therefore, protein-protein interaction mapping is regarded as a
      widely accepted standardized functional genomics technique that provides
      comprehensive functional interpretation of previously uncharacterized proteins. A
      commonly used approach to detecting novel protein-protein interactions is the
      yeast two-hybrid system. In this chapter we describe in detail the protocols used
      to dissect the rice MAPK interactome, including the bait protein auto-activation
      test, identification of a rice MAPK interacting protein, confirmation of
      interaction by retransformation assay and characterization of the novel
      interacting protein.

PMID- 24908131
TI  - Experimental and analytical approaches to characterize plant kinases using
      protein microarrays.
AB  - Comprehensive analysis of protein kinases and cellular signaling pathways
      requires the identification of kinase substrates and interaction partners using
      large-scale amenable approaches. Here, we describe our methods for producing
      plant protein microarrays (PMAs) and discuss various parameters critical to the
      quality of PMAs. Next, we describe methods for detecting protein-protein
      interactions and kinase activity including auto-phosphorylation and substrate
      phosphorylation. We have provided a short video demonstrating how to conduct an
      interaction assay and how to properly handle a protein microarray. Finally, a set
      of analytical methods are presented as a bioinformatics pipeline for the
      acquisition of PMA data and for selecting PMA candidates using statistical
      testing. The experimental and analytical protocols described here outline the
      steps to produce and utilize PMAs to analyze signaling networks. 

PMID- 24908132
TI  - Protein complexes characterization in Arabidopsis thaliana by tandem affinity
      purification coupled to mass spectrometry analysis.
AB  - Proteins are major elements participating in all the key functions of the cells.
      They rarely fulfill their physiological roles in an autonomous way but rather act
      as part of more complex cellular machines. Indeed they can bind different types
      of molecules (proteins, nucleic acids, metabolites, etc.), via stable or
      transient interactions, depending on their nature and functions. The
      identification of the molecular partners of a given protein is hence essential to
      better understand its roles, regulation, and mechanisms of action.This chapter
      describes the use of a tandem affinity purification approach followed by mass
      spectrometry analysis to try to identify and characterize the proteins involved
      in protein complexes in Arabidopsis thaliana and decipher some mechanisms of
      regulation of the modules. Important elements to consider in such an approach are
      first extensively exposed in the introduction. This technique, in combination
      with complementary approaches like yeast two-hybrid and bimolecular fluorescence
      complementation, can be an interesting source of data to identify and
      characterize in vivo protein complexes. 

PMID- 24908133
TI  - Quantitative phosphoproteomic analysis using iTRAQ method.
AB  - The MAPK (mitogen-activated kinase) cascade plays important roles in plant
      perception of and reaction to developmental and environmental cues.
      Phosphoproteomics are useful to identify target proteins regulated by MAPK
      dependent signaling pathway. Here, we introduce the quantitative phosphoproteomic
      analysis using a chemical labeling method. The isobaric tag for relative and
      absolute quantitation (iTRAQ) method is a MS-based technique to quantify protein
      expression among up to eight different samples in one experiment. In this
      technique, peptides were labeled by some stable isotope-coded covalent tags. We
      perform quantitative phosphoproteomics comparing Arabidopsis wild type and a
      stress-responsive mapkk mutant after phytotoxin treatment. To comprehensively
      identify the downstream phosphoproteins of MAPKK, total proteins were extracted
      from phytotoxin-treated wild-type and mapkk mutant plants. The phosphoproteins
      were purified by Pro-Q((r)) Diamond Phosphoprotein Enrichment Kit and were
      digested with trypsin. Resulting peptides were labeled with iTRAQ reagents and
      were quantified and identified by MALDI TOF/TOF analyzer. We identified many
      phosphoproteins that were decreased in the mapkk mutant compared with wild type.

PMID- 24908134
TI  - Blood pressure and cardiovascular effects of new and emerging antidiabetic
      agents.
AB  - Despite remarkable declines in US cardiovascular disease morbidity and mortality
      over the last several decades, the prevalence of risk factors such as type 2
      diabetes and hypertension remains high, associated with increasing obesity rates.
      Although optimal glycemic control remains a primary focus to decrease the disease
      burden, the FDA has issued guidance recommendations for documenting
      cardiovascular disease-related safety with research trials on new antidiabetic
      agents with more demanding requirements compared to past approval of existing
      therapies. This review will discuss the public health impact of type 2 diabetes,
      specifically with comorbid hypertension; mechanisms of action of the newest
      antidiabetic drug classes; and preliminary findings and potential clinical
      significance of the favorable blood pressure and body weight effects of the
      sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor
      agonists; and additionally discuss two recent large cardiovascular outcome trials
      with dipeptidyl peptidase-4 inhibitors. 

PMID- 24908135
TI  - Pediatric hypertensive emergencies.
AB  - Hypertensive emergency is a life-threatening condition that requires immediate
      evaluation and treatment. In children, severe hypertension can be caused by a
      variety of different underlying conditions. It usually presents with neurological
      involvement; however, signs and symptoms of injury to the kidneys, myocardium and
      eyes can also be present. Hospitalization for intravenous treatment with
      antihypertensive(s) and close monitoring in an intensive care setting are
      required for these patients. Few studies in children with hypertensive emergency
      have been done in the last several years. The findings and observations of these
      studies are discussed in this review. 

PMID- 24908138
TI  - A glass microchip device for conducting serological survey of West Nile viral
      antibodies.
AB  - Serological surveys are vital to determining the prevalence of a disease and/or
      the immunity status against it in any population. However, the relatively large
      sample volume requirement (1-10 mL) in traditional serum-based assays demands
      that blood draw camps be set up by medical professionals to obtain samples for
      these studies which significantly increases the time and cost associated with
      them. Here we address these drawbacks of a serosurvey by reducing the whole blood
      requirement in its diagnostic procedures down to 10 MUL using the microfluidic
      platform. Such a miniaturization approach was demonstrated in our current work by
      developing a microchip based serological device for determining the serum levels
      of West Nile (WN) viral antibodies (IgG and IgM) to assess the immunity status
      against WN virus in Fremont County, Wyoming. Enzyme-linked immunosorbent assays
      (ELISA) were developed for these target analytes in glass microchannels to
      accomplish this task using antibodies/assay reagents purchased from commercial
      sources. The reported assays were directly quantitated using a fluorescence
      microplate reader which to our knowledge is the first account of signal
      measurement in a microchip based ELISA procedure using this standard instrument.
      To enable this quantitation method, the assay channels on our device were spaced
      identically as the wells on a commercial microplate, and a holder having the
      dimensions of this plate was used to accommodate the microchips. Our microfluidic
      assays showed an excellent correlation with the results from the microwell plate
      based experiments for significantly lower incubation periods and using only 3 MUL
      of the ELISA reagents. 

PMID- 24908137
TI  - Sustained delivery of MGF peptide from microrods attracts stem cells and reduces
      apoptosis of myocytes.
AB  - Local release of drugs may have many advantages for tissue repair but also
      presents major challenges. Bioengineering approaches allow microstructures to be
      fabricated that contain bioactive peptides for sustained local delivery. Heart
      tissue damage is associated with local increases in mechano growth factor (MGF),
      a member of the IGF-1 family. The E domain of MGF peptide is anti-apoptotic and a
      stem cell homing factor. The objectives of this study were to fabricate a
      microrod delivery device of poly (ethylene glycol) dimethacrylate (PEGDMA)
      hydrogel loaded with MGF peptide and to determine the elution profile and
      bioactivity of MGF. The injectable microrods are 30 kPa stiffness and 15 MUm
      widths by 100 MUm lengths, chosen to match heart stiffness and myocyte size.
      Successful encapsulation of native MGF peptide within microrods was achieved with
      delivery of MGF for 2 weeks, as measured by HPLC. Migration of human mesenchymal
      stem cells (hMSCs) increased with MGF microrod treatment (1.72 +/- 0.23, p <
      0.05). Inhibition of the apoptotic pathway in neonatal rat ventricular myocytes
      was induced by 8 h of hypoxia (1 % O2). Protection from apoptosis by MGF microrod
      treatment was shown by the TUNEL assay and increased Bcl-2 expression (2 +/-
      0.19, p < 0.05). Microrods without MGF regulated the cytoskeleton, adhesion, and
      proliferation of hMSCs, and MGF had no effect on these properties. Therefore, the
      combination microdevice provided both the mechanical cues and 2-week MGF
      bioactivity to reduce apoptosis and recruit stem cells, suggesting potential use
      of MGF microrods for cardiac regeneration therapy in vivo. 

PMID- 24908139
TI  - New antiepileptic drugs and women.
AB  - Since 1990, sixteen new antiepileptic drugs (AEDs) have been introduced. Most of
      these new AEDs have only been insufficiently studied with respect to women
      specific aspects such as endogenous sex hormones, hormonal contraception,
      pregnancy, breastfeeding, or menopause. This is of concern because it has been
      shown for some of the new AEDs that these factors may have a clinically
      significant impact on their pharmacokinetics and seizure control. Also, new AEDs
      may affect hormone homeostasis and pass over into breast milk. The best studied
      of the new AEDs are lamotrigine, levetiracetam and oxcarbazepine. Although
      gabapentin and pregabalin are even more frequently used (due to their therapeutic
      effects in nonepileptic conditions), our understanding of these two drugs in
      relation to women's issues is surprisingly poor. Little to nothing is known about
      zonisamide, retigabine/ezogabine, lacosamide, perampanel and the other new AEDs.
      Nevertheless, many small studies and case series have been published on new AEDs
      and women-specific aspects. This review gives an overview on what is known today.

PMID- 24908140
TI  - Long-term follow-up of adult patients with genetic generalized epilepsy with
      typical absence seizures and generalized paroxysmal fast activity in their EEG.
AB  - PURPOSE: Generalized paroxysmal fast activity (GPFA), an EEG pattern with
      variable frequency and duration, is usually noted in symptomatic/cryptogenic
      generalized epilepsies. However, GPFA has also been reported in a few patients
      with genetic generalized epilepsy (GGE) who presented with typical absence
      seizures (TAS). Our aim was to report the results of long-term follow-up and
      genetic findings in these patients. METHODS: We investigated all EEGs of adult
      GGE patients with TAS, and identified 12 patients with GPFA (8.3% of adult GGE
      patients with TAS). Ten of these patients were available for long-term follow up.
      Their clinical and electroencephalographic courses and genetic features were
      investigated. The control group was composed of 24 adult GGE patients who also
      had TAS, but lacking GPFA with a similar follow-up duration in the same epilepsy
      center. RESULTS: The mean age at GPFA detection was 33+/-16.6 (16-71 years) and
      80% still had GPFA in their last EEG. The duration of epilepsy and persistence of
      TAS were both significantly longer in the GPFA group despite a similar follow-up
      duration. Sixty percent of the GPFA group had consanguineous parents, whereas
      this rate was only 4.17% in the control group. Seven relatives of the GPFA group
      also had epilepsy. We could not show any known mutations in two families. At the
      end of the follow-up, none of the patients with GPFA was dependent in self-care,
      despite continuing seizures. CONCLUSION: Our study shows that GPFA is an ignored
      EEG pattern of adult GGE patients with TAS, indicating a long and non-remitting
      course in almost all of the patients.

PMID- 24908141
TI  - Clinicopathological predictors of poor survival and recurrence after curative
      resection in hepatocellular carcinoma without portal vein tumor thrombosis.
AB  - Many factors associated with long-term outcome in hepatocellular carcinoma (HCC)
      with portal vein tumor thrombosis (PVTT) were previously identified. However,
      those in HCC without PVTT have not been elucidated. This study was designed to
      define the risk factors of poor post-surgical survival and recurrence in this
      subgroup of HCC. Medical records and follow-up data of consecutive 152 patients
      with PVTT-absent HCC underwent curative resection were reviewed. The impacts of
      clinical and pathological variables on patient survival and recurrence were
      evaluated by univariate and multivariate analyses. It was shown that Edmondson
      Steiner grade, TNM stage, microvascular invasion (MVI), satellite nodule, serum
      AFP level, tumor size and number were significant for tumor-specific and/or tumor
      free survival in univariate analysis. Among them, Edmondson-Steiner grade and TNM
      stage were of independent significances for both, whereas satellite nodule
      independently predicted tumor-free survival. In Chi-square test, Edmondson
      Steiner grade, TNM stage and MVI were significantly related to overall as well as
      early recurrence. Stepwise logistic regression identified Edmondson-Steiner grade
      as the single independent predictor of both. To be summarized, variables that are
      associated with poor prognosis and recurrence in HCC without PVTT are all tumor
      related ones. Of these, differentiation degree might be of particular importance.

PMID- 24908142
TI  - BRAF-mutated microsatellite stable colorectal carcinoma: an aggressive
      adenocarcinoma with reduced CDX2 and increased cytokeratin 7 immunohistochemical
      expression.
AB  - Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal carcinoma with
      BRAF mutation and high-level microsatellite instability (MSI-H) has been well
      documented. The immunophenotype of BRAF-mutated microsatellite stable (MSS)
      colorectal carcinoma has not been reported. We analyzed 205 colorectal carcinomas
      including 28 BRAF-mutated MSS, 53 BRAF-mutated MSI-H, and 124 BRAF wild-type MSS
      tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression.
      CDX2 was scored semiquantitatively for both staining intensity and percent of
      tumor cells staining and a modified CDX2 H-score was calculated. Patients with
      BRAF-mutated MSS colorectal carcinomas were more frequently stage IV at
      presentation compared to patients with BRAF-mutated MSI-H colorectal carcinomas
      and BRAF wild-type MSS colorectal carcinomas (32% versus 8% versus 15%, P <
      .001). BRAF-mutated MSS colorectal carcinoma displayed reduced CDX2 expression
      compared to BRAF wild-type MSS colorectal carcinoma (75% versus 94%; mean CDX2 H
      score 98 versus 150, P < .001). CK7 expression was more often identified in BRAF
      mutated MSS colorectal carcinoma compared to both BRAF-mutated MSI-H colorectal
      carcinoma and BRAF wild-type MSS colorectal carcinoma (39% versus 6% versus 6%, P
      = .0001). BRAF-mutated MSI-H colorectal carcinomas were less often CK20 positive
      compared to BRAF-mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus
      90%, P = 0.001). In summary, BRAF-mutated MSS colorectal carcinoma often displays
      reduced CDX2 and increased CK7 expression. Knowledge of this altered
      immunophenotype is important as patients with BRAF-mutated MSS colorectal
      carcinoma often present with metastatic disease and the altered tumor
      immunophenotype may lead to the erroneous assumption that origin from the
      colon/rectum is unlikely.

PMID- 24908143
TI  - Molecular profiling of soft tissue sarcomas using next-generation sequencing: a
      pilot study toward precision therapeutics.
AB  - Next-generation sequencing (NGS) can provide in-depth detection of numerous gene
      alterations. To date, there are very few reports describing the use of this
      technique in soft tissue sarcomas. Herein, we aim to test the utility of NGS in
      identifying targetable mutations in these tumors. NGS was performed using a
      clinically validated multiplexed gene sequencing panel interrogating the full
      coding sequence of 194 cancer-related genes. A custom bioinformatics pipeline was
      developed to detect all classes of mutations directly from the NGS data,
      including single-nucleotide variants, small insertions and deletions, copy number
      variation, and complex structural variations. Twenty-five soft tissue sarcomas
      were analyzed; 18 of these patients had metastatic disease and 7 primary locally
      advanced tumors. Targetable mutations for which clinical trials are available
      were identified in 60% of the cases. MAP2K4, AURKA, AURKB, and c-MYC
      amplification were recurrent events in leiomyosarcomas. Frequent non-targetable
      variants included copy losses of the TP53 (24%), PTEN (16%), and CDKN2A (20%).
      Additional frameshift mutations, deletion mutations, and single-nucleotide
      variants involving numerous genes, including RB1, NOTCH1, PIK3CA, PDGFRB, EPHA5,
      KDM6A, NF1, and FLT4 genes, were also identified. NGS is useful in identifying
      targetable mutations in soft tissue sarcomas that can serve as a rationale for
      inclusion of patients with advanced disease in ongoing clinical trials and allow
      for better risk stratification. 

PMID- 24908144
TI  - Photorhabdus luminescens toxins TccC3 and TccC5: insecticidal ADP
      ribosyltransferases that modify threonine and glutamine.
AB  - The ADP-ribosyltransferases TccC3 and TccC5 are the biologically active TcC
      components of the tripartite Photorhabdus luminescens Tc toxin, which consist of
      TcA, TcB, and TcC components. TcA is the binding and membrane translocation
      component. TcB is a functional linker between TcC and TcA and also involved in
      the translocation of the toxin. While TccC3 ADP-ribosylates actin at threonine
      148, TccC5 modifies Rho proteins at glutamine 61/63. Both modifications result in
      major alteration of the actin cytoskeleton. Here we discuss structure and
      function of the Tc toxin and compare its ADP-ribosyltransferase activities with
      other types of actin and Rho modifying toxins. 

PMID- 24908148
TI  - Diazepam and Jacobson's progressive relaxation show similar attenuating short
      term effects on stress-related brain glucose consumption.
AB  - A non-pharmacological method to reduce anxiety is "progressive relaxation" (PR).
      The aim of the method is to reduce mental stress and associated mental processes
      by means of progressive suppression of muscle tension. The study was addressed to
      evaluate changes in brain glucose metabolism induced by PR in patients under a
      stressing state generated by a diagnostic medical intervention. The effect of PR
      was compared to a dose of sublingual diazepam, with the prediction that both
      interventions would be associated with a reduction in brain metabolism. Eighty
      four oncological patients were assessed with 18F-fluorodeoxyglucose-positron
      emission tomography. Maps of brain glucose distribution from 28 patients
      receiving PR were compared with maps from 28 patients receiving sublingual
      diazepam and with 28 patients with no treatment intervention. Compared to
      reference control subjects, the PR and diazepam groups showed a statistically
      significant, bilateral and generalized cortical hypometabolism. Regions showing
      the most prominent changes were the prefrontal cortex and anterior cingulate
      cortex. No significant differences were identified in the direct comparison
      between relaxation technique and sublingual diazepam. Our findings suggest that
      relaxation induced by a physical/psychological procedure can be as effective as a
      reference anxiolytic in reducing brain activity during a stressful state. 

PMID- 24908149
TI  - Father-daughter relationship and the severity of eating disorders.
AB  - BACKGROUND: Mother-daughter relationship was the focus of studies on the
      development of eating disorders (ED) for many years. This study aimed to examine
      the association between the father-daughter relationship and ED and depressive
      symptoms. METHODS: Fifty-three women diagnosed with ED were compared to a
      psychiatric control group (n=26) and to healthy participants (n=60) regarding
      their perception of their fathers and the relationship with them. Assessments
      were done using the Parental Bonding Instrument, the Eating Disorders
      Questionnaire, the Body Shape Questionnaire, the Eating Attitude Test, and the
      Beck Depression Inventory as well as narrative-based methods. RESULTS: Fathers'
      negative attributes were significantly associated with ED and depressive symptom.
      Two profiles of father-daughter relationship were found, the "caring and
      benevolent" relationship and the "overprotective and avoidant" one. In the
      latter, patients displayed significantly higher levels of food-restraint, more
      concerns about eating and about their body shape and appearance, and higher
      levels of depression. DISCUSSION: Negative perception of the father's parenting
      style as well as the quality of the relationship with him are crucial for the
      understanding of the development and persistence of ED. Therapeutic programs for
      ED should focus not only on the relationship with the mother but must also
      address the relationship with the father.

PMID- 24908147
TI  - Effects of early-life exposure to allergens and bacteria on recurrent wheeze and
      atopy in urban children.
AB  - BACKGROUND: Wheezing illnesses cause major morbidity in infants and are frequent
      precursors to asthma. OBJECTIVE: We sought to examine environmental factors
      associated with recurrent wheezing in inner-city environments. METHODS: The Urban
      Environment and Childhood Asthma study examined a birth cohort at high risk for
      asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental
      assessments included allergen exposure and, in a nested case-control study of 104
      children, the bacterial content of house dust collected in the first year of
      life. Associations were determined among environmental factors, aeroallergen
      sensitization, and recurrent wheezing at age 3 years. RESULTS: Cumulative
      allergen exposure over the first 3 years was associated with allergic
      sensitization, and sensitization at age 3 years was related to recurrent wheeze.
      In contrast, first-year exposure to cockroach, mouse, and cat allergens was
      negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75,
      respectively; P <= .01). Differences in house dust bacterial content in the first
      year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was
      associated with atopy and atopic wheeze. Exposure to high levels of both
      allergens and this subset of bacteria in the first year of life was most common
      among children without atopy or wheeze. CONCLUSIONS: In inner-city environments
      children with the highest exposure to specific allergens and bacteria during
      their first year were least likely to have recurrent wheeze and allergic
      sensitization. These findings suggest that concomitant exposure to high levels of
      certain allergens and bacteria in early life might be beneficial and suggest new
      preventive strategies for wheezing and allergic diseases.

PMID- 24908150
TI  - Links between sleep and body mass index in bipolar disorders: an exploratory
      study.
AB  - STUDY OBJECTIVES: Obesity and excess bodyweight are highly prevalent in
      individuals with bipolar disorders (BD) and are associated with adverse
      consequences. Multiple factors may explain increased bodyweight in BD including
      side effects of psychotropic medications, and reduced physical activity. Research
      in the general population demonstrates that sleep disturbances may also
      contribute to metabolic burden. We present a cross-sectional study of the
      associations between body mass index (BMI) and sleep parameters in patients with
      BD as compared with healthy controls (HC). METHODS: Twenty-six French outpatients
      with remitted BD and 29 HC with a similar BMI completed a 21-day study of sleep
      parameters using objective (actigraphy) and subjective (PSQI: Pittsburgh Sleep
      Quality Index) assessments. RESULTS: In BD cases, but not in HC, higher BMI was
      significantly correlated with lower sleep efficiency (P=0.009) and with several
      other sleep parameters: shorter total sleep time (P=0.01), longer sleep onset
      latency (P=0.05), higher fragmentation index (P=0.008), higher inter-day
      variability (P=0.05) and higher PSQI total score (P=0.004). CONCLUSIONS: The
      findings suggest a link between a high BMI and several sleep disturbances in BD,
      including lower sleep efficiency. Physiological mechanisms in BD cases may
      include an exaggeration of phenomena observed in non-clinical populations.
      However, larger scale studies are required to clarify the links between metabolic
      and sleep-wake cycle disturbances in BD.

PMID- 24908151
TI  - Religiosity is a protective factor against self-injurious thoughts and behaviors
      in Jewish adolescents: findings from a nationally representative survey.
AB  - PURPOSE: Few studies have investigated the association between religiosity and
      self-injurious thoughts and behaviors specifically in adolescents, yielding
      inconsistent results. To date, no study has examined this relationship in a
      Jewish adolescent cohort. METHODS: Self-injurious thoughts and behaviors, as well
      as depression, were assessed in a nationally representative sample of Jewish
      adolescents (n=620) and their mothers, using the Development and Well-Being
      Assessment Inventory (DAWBA) structured interview. Degree of religiosity was
      obtained by a self-report measure. RESULTS: Using multivariate analysis, level of
      religiosity was inversely associated with self-injurious thoughts and behaviors
      (Wald chi(2)=3.95, P=0.047), decreasing the likelihood of occurrence by 55%
      (OR=0.45, 95% CI 0.2-0.99), after adjusting for depression and socio-demographic
      factors. This model (adjusted R(2)=0.164; likelihood ratio chi(2)=7.59; df=1;
      P<0.047) was able to correctly classify 95.6% of the patients as belonging either
      to the high or low risk groups. CONCLUSION: This is the first study demonstrating
      religiosity to have a direct independent protective effect against self-injurious
      thoughts and behaviors in Jewish adolescents. This finding has clinical
      implications regarding risk assessment and suicide prevention. Further research
      can potentially elucidate the complex relationship between religiosity, self
      injury and suicide in this population.

PMID- 24908152
TI  - Separation anxiety disorder in adult patients with obsessive-compulsive disorder:
      prevalence and clinical correlates.
AB  - OBJECTIVE: Individuals with obsessive-compulsive disorder (OCD) and separation
      anxiety disorder (SAD) tend to present higher morbidity than do those with OCD
      alone. However, the relationship between OCD and SAD has yet to be fully
      explored. METHOD: This was a cross-sectional study using multiple logistic
      regression to identify differences between OCD patients with SAD (OCD+SAD, n=260)
      and without SAD (OCD, n=695), in terms of clinical and socio-demographic
      variables. Data were extracted from those collected between 2005 and 2009 via the
      Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders project.
      RESULTS: SAD was currently present in only 42 (4.4%) of the patients, although
      260 (27.2%) had a lifetime diagnosis of the disorder. In comparison with the OCD
      group patients, patients with SAD+OCD showed higher chance to present sensory
      phenomena, to undergo psychotherapy, and to have more psychiatric comorbidities,
      mainly bulimia. CONCLUSION: In patients with primary OCD, comorbid SAD might be
      related to greater personal dysfunction and a poorer response to treatment, since
      sensory phenomena may be a confounding aspect on diagnosis and therapeutics.
      Patients with OCD+SAD might be more prone to developing specific psychiatric
      comorbidities, especially bulimia. Our results suggest that SAD symptom
      assessment should be included in the management and prognostic evaluation of OCD,
      although the psychobiological role that such symptoms play in OCD merits further
      investigation.

PMID- 24908153
TI  - Effect of content of chiral selector and pore size of core-shell type silica
      support on the performance of amylose tris(3,5-dimethylphenylcarbamate)-based
      chiral stationary phases in nano-liquid chromatography and capillary
      electrochromatography.
AB  - In this study the separation performance of various chiral stationary phases
      (CSPs) made of polysaccharide-based chiral selectors coated onto superficially
      porous (core-shell or fused-core) silica supports were evaluated. The CSPs
      obtained by coating of various amounts of chiral selector (1-5%) onto supports of
      various pore size (100 and 300 A) were studied. Their evaluation was pursued in
      both chiral nano-liquid chromatography (nano-LC) and chiral capillary
      electrochromatography (CEC). Among the goals of this study was to re-examine our
      previous unexpected finding of better performance of superficially porous CSP
      under CEC conditions compared to nano-LC conditions for a new set of chiral
      compounds, as well as to study the effect of varying the chiral selector content
      and nominal pore size of supporting silica on the performance of core-shell
      silica-based polysaccharide-type CSPs. Based on the results of this study it can
      be seen that CSPs based on superficially porous silica can successfully be used
      for the separation of enantiomers in both nano-LC and CEC mode. Only a slight
      advantage of CEC over nano-LC mode was observed in this study from the viewpoint
      of plate numbers, especially at higher mobile phase flow rates. It must also be
      noted that the optimal theoretical plate height is still too high and further
      optimization of superficially porous CSPs is necessary for both nano-LC and CEC
      applications.

PMID- 24908154
TI  - Cloud point sample clean-up and capillary zone electrophoresis with field
      enhanced sample injection and micelle to solvent stacking for the analysis of
      herbicides in milk.
AB  - Sample clean-up by cloud point phase separation and analysis by capillary
      electrophoresis with stacking was developed for quaternary ammonium herbicides
      (i.e., paraquat and diquat) in milk. For sample clean-up, a mixture of 845MUL of
      milk sample, 5MUL of 100mM phosphoric acid, and 150MUL of Triton X-114 was heated
      (60 degrees C for 2min) and centrifugated (3000rpm for 2min) in 2-mL Eppendorf
      tube. The upper phase was directly analysed by capillary electrophoresis via
      electrokinetic injection at 10kV for 150s. The separation electrolyte was 100mM
      phosphate buffer with 20% acetonitrile at pH 2.5. Before sample injection, a
      micellar solution (10mM SDS in 80mM phosphate buffer at pH 2.5) and an organic
      solvent rich solution (30% ACN) was hydrodynamically introduced into the
      capillary. These solutions provided the necessary conditions for stacking the
      cationic herbicides via the combination of field enhanced sample injection and
      micelle to solvent stacking. The LODs (S/N=3) obtained from the entire strategy
      for paraquat and diquat in milk was 0.004 and 0.018MUg/mL, respectively. This is
      1.5 to >2 orders of magnitude better than the corresponding LODs obtained from
      the electrophoretic analysis of herbicide standards prepared in the separation
      electrolyte. The strategy was also successfully applied to 5 milk samples
      available in the market. 

PMID- 24908155
TI  - Electrospun polystyrene/oxidized carbon nanotubes film as both sorbent for thin
      film microextraction and matrix for matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry.
AB  - In the current study, polystyrene/oxidized carbon nanotubes (PS/OCNTs) film was
      prepared and applied as both an adsorbent of thin film microextraction (TFME) and
      matrix for matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS) for the first time. The uniform size of PS/OCNTs film
      with OCNTs evenly and firmly immobilized in PS was obtained by electrospinning.
      And a novel TFME device was developed using the prepared PS/OCNTs film to enrich
      benzo[a]pyrene (BaP) from water, and also BaP and 1-hydroxypyrene (1-OHP) from
      urine sample. Then the extracted analytes on the PS/OCNTs film were directly
      applied to MALDI-MS analysis with PS/OCNTs film as the MALDI matrix. Our results
      show that PS/OCNTs film is a good TFME adsorbent toward the analytes and an
      excellent matrix for the sensitive determination of BaP and 1-OHP using MALDI-TOF
      MS. The employment of PS/OCNTs as the matrix for MALDI can effectively avoid the
      large variation of signal intensity normally resulting from heterogeneous
      distribution of the adsorbed analyte on matrix layer, which therefore
      significantly improve spot-to-spot reproducibility. The introduction of PS in the
      film can prevent OCNTs from flying out of MALDI plate to damage the equipment. In
      addition, PS/OCNTs film also largely extended the duration of ion signal of
      target analyte compared to OCNTs matrix. The developed method was further
      successfully used to quantitatively determine BaP in environmental water and 1
      OHP in urine samples. The results show that BaP and 1-OHP could be easily
      detected at concentrations of 50pgmL(-1) and 500pgmL(-1), respectively,
      indicating the high detection sensitivity of this method. For BaP analysis, the
      linear range was 0.1-20ngmL(-1) with a correlation coefficient of 0.9970 and the
      recoveries were in the range of 81.3 to 123.4% with the RSD<=8.5% (n=3); for
      urinary 1-OHP analysis, the linear range was 0.5-20ngmL(-1) with a correlation
      coefficient of 0.9937 and the recoveries were in the range of 79.2 to 103.4% with
      the RSD<=7.6% (n=3). Taken together, the developed method provides a simple,
      rapid, cost-effective and high-throughput approach for the analysis of BaP in
      environmental water and endogenous 1-OHP in urine samples. 

PMID- 24908158
TI  - Functional connectivity between right and left mesial temporal structures.
AB  - The aim of this study is to investigate functional connectivity between right and
      left mesial temporal structures using cerebrocerebral evoked potentials. We
      studied seven patients with drug-resistant focal epilepsy who were explored with
      stereotactically implanted depth electrodes in bilateral hippocampi. In all
      patients cerebrocerebral evoked potentials evoked by stimulation of the fornix
      were evaluated as part of a research project assessing fornix stimulation for
      control of hippocampal seizures. Stimulation of the fornix elicited responses in
      the ipsilateral hippocampus in all patients with a mean latency of 4.6 ms (range
      2-7 ms). Two patients (29 %) also had contralateral hippocampus responses with a
      mean latency of 7.5 ms (range 5-12 ms) and without involvement of the
      contralateral temporal neocortex or amygdala. This study confirms the existence
      of connections between bilateral mesial temporal structures in some patients and
      explains seizure discharge spreading between homotopic mesial temporal structures
      without neocortical involvement.

PMID- 24908156
TI  - Effects of the compounds resveratrol, rutin, quercetin, and quercetin
      nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice.
AB  - Oxaliplatin (OXA) is a platinum compound widely used in the treatment of some
      solid tumors, especially colorectal cancer. Despite its usefulness, oxaliplatin
      associated neurotoxicity represents the main dose-limiting factor of this drug,
      and until now, there is no suitable treatment. Chemotherapy with oxaliplatin also
      increases the rate of developing hepatic damages with inflammatory activity,
      termed chemotherapy-associated steatohepatitis (CASH). In the present study, we
      aimed to compare the effects of a series of antioxidant compounds on simultaneous
      development of oxaliplatin-induced hepato- and neurotoxicity in mice. Mice BALB/c
      were treated with oxaliplatin for 6 weeks, 10 mg/kg, intraperitoneally, resulting
      in mechanical allodynia and hepatic steatosis. We administered the following
      antioxidant compounds--rutin (RT) (20 mg/kg), resveratrol (RVS) (100 mg/kg),
      quercetin (QT) (20 mg/kg), and quercetin nanoemulsion (NQT) (20 mg/kg)--daily by
      gavage to BALB/c, and N-acetylcysteine (NAC) was used as positive control.
      Treatments with RSV, RUT, or NQT were able to prevent mechanical allodynia when
      compared to the OXA group, and this effect was associated with decreased c-Fos
      immunopositivity in the lumbar spinal cord. Regarding the effects on
      steatohepatitis, RVS, QT, and NQT almost completely reversed the mean liver
      weight increase induced by OXA. In accordance with these previous data,
      histological evaluation indicated attenuation of all features of hepatic
      steatosis evaluated in RSV, RUT, QT, and NQT groups. These compounds were able to
      reduce the immunopositivity for the apoptosis marker caspase-3. On the other
      hand, only QT and NQT treatments were able to reduce neutrophil migration
      measured by myeloperoxidase (MPO) activity. These results suggest that the
      compounds tested, RSV, RUT, QT, and NQT, would be useful for the clinical
      treatment of neuro- and hepatoxicity induced by oxaliplatin.

PMID- 24908159
TI  - Fetal surgery for myelomeningocele is effective: a critical look at the whys.
AB  - Formerly, the disastrous cluster of neurologic deficits and associated neurogenic
      problems in patients with myelomeningocele (MMC) was generally thought to solely
      result from the primary malformation, i.e., failure of neurulation. Today,
      however, there is no doubt that a dimensional additional pathogenic mechanism
      exists. Most likely, it contributes much more to loss of neurologic function than
      non-neurulation does. Today, there is a large body of compelling experimental and
      clinical evidence confirming that the exposed part of the non-neurulated spinal
      cord is progressively destroyed during gestation, particularly so in the third
      trimester. These considerations gave rise to the two-hit-pathogenesis of MMC with
      non-neurulation being the first and consecutive in utero acquired neural tissue
      destruction being the second hit. This novel pathophysiologic understanding has
      obviously triggered the question whether the serious and irreversible functional
      loss caused by the second hit could not be prevented or, at least, significantly
      alleviated by timely protecting the exposed spinal cord segments, i.e., by early
      in utero repair of the MMC lesion. Based on this intriguing hypothesis and the
      above-mentioned data, human fetal surgery for MMC was born in the late nineties
      of the last century and has made its way to become a novel standard of care,
      particularly after the so-called "MOMS Trial". This trial, published in the New
      England Journal of Medicine, has indisputably shown that overall, open prenatal
      repair is distinctly better than postnatal care alone. Finally, a number of
      important other topics deserve being mentioned, including the necessity to work
      on the up till now immature endoscopic fetal repair technique and the need for
      concentration of these extremely challenging cases to a small number of really
      qualified fetal surgery centers worldwide. In conclusion, despite the fact that
      in utero repair of MMC is not a complete cure and not free of risk for both
      mother and fetus, current data clearly demonstrate that open fetal-maternal
      surgery is to be recommended as novel standard of care when pregnancy is to be
      continued and when respective criteria for the intervention before birth are met.
      Undoubtedly, it is imperative to inform expecting mothers about the option of
      prenatal surgery once their fetus is diagnosed with open spina bifida. 

PMID- 24908161
TI  - Re: Mono- versus polyaxial locking plates in distal femur fractures: a
      prospective randomized multicentre clinical trial.

PMID- 24908160
TI  - Analytical approaches in microRNA therapeutics.
AB  - MicroRNAs are non-coding oligonucleotides with regulatory roles in virtually all
      biological processes. Deregulation of microRNAs lead to impaired cellular
      function and disease development. Thus, microRNAs are of potential diagnostic and
      therapeutic relevance. Several technology platforms are currently available for
      quantitative microRNA analysis and profiling, including the most extensively used
      PCR-based methods. Each of these technologies has its own advantages and
      limitations. Mass spectrometry combines low-level detectability with high
      selectivity and has been used for oligonucleotide sequence analysis. Its use for
      native microRNA analysis has been limited due to the very low abundance and
      chemical similarity of microRNAs. However, with the advancement of technology,
      this analytical method has become a powerful complementary tool for comprehensive
      analysis of native and synthetic microRNAs. This brief review highlights current
      developments in the field of microRNA analytics, detection techniques for
      extracellular microRNAs, their synthetic inhibitors, and the dynamics of their
      interactions. 

PMID- 24908162
TI  - Fracture resistance of three porcelain-layered CAD/CAM zirconia frame designs.
AB  - OBJECTIVES: Chipping is the most frequent clinical failure of zirconia crowns.
      Causes of chipping have not been completely understood and different possible
      reasons have been considered. The study was aimed at evaluating the fracture
      resistance of 3 different CAD/CAM zirconia frame designs veneered with porcelain.
      METHODS: Thirty extracted sound premolars were divided into 3 groups (n=10).
      Chamfer preparations were performed, impressions were taken. Three zirconia frame
      designs (Aadva, GC) were realized: reproduction of the abutment contour (flat
      design, FD); wax-up as for porcelain-fused-to-metal crowns (PFM); anatomically
      guided, designed to keep constant the thickness of the overlying porcelain
      veneering (AG). Porcelain veneering was made with pressure layering technique
      (Initial Zr, GC). Crowns were cemented utilizing a self-adhesive resin cement (G
      Cem, GC). After a 24-h water storage at 37 degrees C, using a universal testing
      machine (1 mm crosshead speed), crowned teeth were loaded in the central fossa in
      a direction parallel to the longitudinal axis of the tooth. Load at fracture was
      recorded in Newtons (N). Digital photographs of the specimens were taken in order
      to assess failure patterns. Between-group differences in fracture strength were
      statistically analyzed (One-Way Analysis of Variance, Tukey test, p<0.05).
      RESULT: Load at fractures differed significantly among the groups (p=0.004). AG
      exhibited significantly higher fracture resistance 1721.6 (488.1) N than PFM
      1004.6 (321.3) N and FD 1179.5 (536.2) N, that were comparable. Repairable
      failures occurred in 80% of AG, 70% of PFM, and 50% of FD specimens.
      SIGNIFICANCE: Anatomically guided zirconia frames resisted significantly higher
      loads than flat and PFM-like frame designs.

PMID- 24908163
TI  - Riparoside B and timosaponin J, two steroidal glycosides from Smilax riparia,
      resist to hyperuricemia based on URAT1 in hyperuricemic mice.
AB  - The roots and rhizomes of Smilax riparia (SR), called "Niu-Wei-Cai" in
      traditional Chinese medicine (TCM), are believed to be effective in treating gout
      symptoms. However, it is not clear if the active constituents and uricosuric
      mechanisms of S. riparia support its therapeutic activities. In this study, we
      isolated two steroidal glycosides named riparoside B and timosaponin J from the
      total saponins of S. riparia. We then examined if these two compounds were
      effective in reducing serum uric acid levels in a hyperuricemic mouse model
      induced by potassium oxonate. We found that the two steroidal glycosides possess
      potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1
      mainly and inhibiting XOD activity in a certain extent, which contribute to the
      enhancement of uric acid excretion and attenuate hyperuricemia-induced renal
      dysfunction. Riparoside B and timosaponin J may have a clinical utility in
      treating gout and other medical conditions caused by hyperuricemia. 

PMID- 24908164
TI  - Graduating general surgery resident operative confidence: perspective from a
      national survey.
AB  - BACKGROUND: General surgical training has changed significantly over the last
      decade with work hour restrictions, increasing subspecialization, the expanding
      use of minimally invasive techniques, and nonoperative management for solid organ
      trauma. Given these changes, this study was undertaken to assess the confidence
      of graduating general surgery residents in performing open surgical operations
      and to determine factors associated with increased confidence. METHODS: A survey
      was developed and sent to general surgery residents nationally. We queried them
      regarding demographics and program characteristics, asked them to rate their
      confidence (rated 1-5 on a Likert scale) in performing open surgical procedures
      and compared those who indicated confidence with those who did not. RESULTS: We
      received 653 responses from the fifth year (postgraduate year 5) surgical
      residents: 69% male, 68% from university programs, and 51% from programs
      affiliated with a Veterans Affairs hospital; 22% from small programs, 34% from
      medium programs, and 44% from large programs. Anticipated postresidency operative
      confidence was 72%. More than 25% of residents reported a lack of confidence in
      performing eight of the 13 operations they were queried about. Training at a
      university program, a large program, dedicated research years, future fellowship
      plans, and training at a program that performed a large percentage of operations
      laparoscopically was associated with decreased confidence in performing a number
      of open surgical procedures. Increased surgical volume was associated with
      increased operative confidence. Confidence in performing open surgery also varied
      regionally. CONCLUSIONS: Graduating surgical residents indicated a significant
      lack of confidence in performing a variety of open surgical procedures. This
      decreased confidence was associated with age, operative volume as well as type,
      and location of training program. Analyzing and addressing this confidence
      deficit merits further study.

PMID- 24908165
TI  - Seizure resistance without parkinsonism in aged mice after tau reduction.
AB  - Tau is an emerging target for Alzheimer's disease (AD) and other conditions with
      epileptiform activity. Genetic tau reduction (in Tau(+/-) and Tau(-/-) mice)
      prevents deficits in AD models and has an excitoprotective effect, increasing
      resistance to seizures, without causing apparent neuronal dysfunction. However,
      most studies of tau reduction have been conducted in <1-year-old mice, and the
      effects of tau reduction in aged mice are less clear. Specifically, whether the
      excitoprotective effects of tau reduction persist with aging is unknown and
      whether tau reduction causes neuronal dysfunction, including parkinsonism, with
      aging is controversial. Here, we performed a comprehensive analysis of 2-year-old
      Tau(+/+), Tau(+/-), and Tau(-/-) mice. In aged mice, tau reduction still
      conferred resistance to pentylenetetrazole-induced seizures. Moreover, tau
      reduction did not cause parkinsonian abnormalities in dopamine levels or motor
      function and did not cause iron accumulation or impaired cognition, although Tau(
      /-) mice had mild hyperactivity and decreased brain weight. Importantly, the
      excitoprotective effect in aged Tau(+/-) mice was not accompanied by detectable
      abnormalities, indicating that partially reducing tau or blocking its function
      may be a safe and effective therapeutic approach for AD and other conditions with
      increased excitability. 

PMID- 24908166
TI  - Age-related changes in the subcortical-cortical encoding and categorical
      perception of speech.
AB  - Aging is associated with declines in auditory processing including speech
      comprehension abilities. Here, we evaluated both brainstem and cortical speech
      evoked brain responses to elucidate how aging impacts the neural transcription
      and transfer of speech information between functional levels of the auditory
      nervous system. Behaviorally, older adults showed slower, more variable speech
      classification performance than younger listeners, which coincided with reduced
      brainstem amplitude and increased, but delayed, cortical speech-evoked responses.
      Mild age-related hearing loss showed differential correspondence with
      neurophysiological responses showing negative (brainstem) and positive (cortical)
      correlations with brain activity. Spontaneous brain activity, that is, "neural
      noise," did not differ between older and younger adults. Yet, mutual information
      and correlations computed between brainstem and cortex revealed higher redundancy
      (i.e., lower interdependence) in speech information transferred along the
      auditory pathway implying less neural flexibility in older adults. Results are
      consistent with the notion that weakened speech encoding in brainstem is
      overcompensated by increased cortical dysinhibition in the aging brain. Findings
      suggest aging negatively impacts speech listening abilities by distorting the
      hierarchy of speech representations, reducing neural flexibility through
      increased neural redundancy, and ultimately impairing the acoustic-phonetic
      mapping necessary for robust speech understanding. 

PMID- 24908167
TI  - Age-related decline in the responsiveness of motor cortex to plastic forces
      reverses with levodopa or cerebellar stimulation.
AB  - The plasticity of motor cortex is integral for motor memory and skills
      acquisition but it declines with aging. Forty healthy volunteers, across 6
      decades, were tested to examine the (a) age-dependency of motor cortex
      responsiveness to plasticity induction, as measured from the response to paired
      associative stimulation (PAS) and the (b) effect of aging on the cerebellar
      modulation of motor cortex response to PAS. We examined if reduced dopaminergic
      transmission was involved in the age-related decline of response to PAS by
      retesting 10 of the older subjects after a single dose of levodopa. There was a
      substantial decline in the motor cortex response to PAS with aging, which was
      restored by levodopa in the older subjects. The cerebellar modulation of motor
      cortex response to PAS was less vulnerable to aging and a single session of
      cerebellar inhibition reinstated the cortical responsiveness in older subjects.
      Both levodopa and cerebellar inhibition can be tested for their ability to
      enhance motor skills acquisition and motor performance in the elderly
      individuals. 

PMID- 24908168
TI  - ABCA7 gene and the risk of Alzheimer's disease in Han Chinese in Taiwan.
AB  - The ATP-binding cassette, subfamily A, member 7 gene (ABCA7) was recently
      identified as a susceptible gene of Alzheimer's disease (AD) in the Caucasian
      population and African Americans. To test its genetic effect in the Han-Chinese
      population, 536 AD cases and 307 cognitive-intact, elder controls were genotyped
      for ABCA7 rs3764650 and apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4
      alleles. Global cognitive performance was assessed by the Mini-Mental State
      Examination in both AD patients and controls. For AD patients, comprehensive
      evaluation of each cognitive domain was further conducted as the following: (1)
      attention (forward and backward digit span); (2) memory (12-item word recall
      test); (3) executive function (category verbal fluency); (4) processing speed
      (Trail making test, part A); and (5) naming task (Boston naming test). ABCA7
      rs3764650 was significantly associated with AD and the GG genotype carried a
      reduced risk for AD (odds ratio = 0.52, p = 0.0026). The association was further
      confirmed in 1802 population-based, healthy controls from Taiwan Biobank as a
      replicate (odds ratio = 0.70, p = 0.032). After adjustment of age, sex, and APOE
      epsilon4 allele, rs3764650 remained to be an independent predictor of AD (p =
      0.001). The influence of ABCA7 was only evident in individuals without APOE
      epsilon4 alleles (p = 0.0004) but absent in epsilon4 carriers (p = 0.91). None of
      the cognitive tests was related to ABCA7 rs3764650 genotypes. The minor allele
      frequency and effect size of rs3764650 disclosed in the Han-Chinese population
      differed from those reported in the Caucasians and African Americans. Further
      studies were warranted to elucidate ABCA7's effect among different ethnic groups.

PMID- 24908169
TI  - Extensive molecular genetic survey of Taiwanese patients with amyotrophic lateral
      sclerosis.
AB  - Identification of genetic mutations has been of burgeoning importance in
      amyotrophic lateral sclerosis (ALS) in recent years. The aim of this study was to
      determine the frequency and spectrum of mutations in major ALS-causing genes in a
      Taiwanese ALS cohort of Han Chinese origin. Mutational analyses of the SOD1,
      TARDBP, FUS, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, and HNRNPA2B1 genes were
      carried out by direct sequencing in 161 unrelated patients with ALS, including 30
      with familial ALS (FALS) and 131 with sporadic ALS (SALS). The CAG repeat size in
      ATXN2 and the GGGGCC repeat expansion in C9ORF72 of the patients were also
      investigated. Mutations were identified in 33 patients (20.5%, 33/161), including
      22 with FALS and 11 with SALS. Mutations were identified most frequently in SOD1
      (7.5%). Three mutations are novel, including SOD1 p.G10A, SOD1 p.D83N, and OPTN
      p.L494W. These findings broaden the spectrum of ALS-causing mutations and are
      indispensable for designing optimal strategies of mutational analysis and genetic
      counseling of ALS for patients of Chinese origin. 

PMID- 24908170
TI  - The effect of age and time to death on primary care costs: the Italian
      experience.
AB  - A large body of literature shows that time to death (TTD) is by far a better
      predictor of health spending than age. In this paper, we investigate if this
      finding holds true also in presence of primary care costs (pharmaceuticals,
      diagnostic tests and specialist visits) in Italy, where they represent an
      important share (about 30%) of the total health care expenditure (HCE). Our
      analysis is based on a large sample of the Italian population (about 750,000
      individuals), obtained from the Health Search-SiSSI database, which contains
      patient-level data collected routinely by General Practitioners in Italy since
      2002. We study individuals aged 19 and older, over the period 2006-2009. By means
      of a two-part model which accounts for the presence of zero expenditure, our
      findings show that age represents the most important driver of primary care costs
      in Italy, although TTD remains a good predictor. These results suggest that age
      and TTD can have a different role in shaping health care costs according to the
      component of health expenditure examined. Therefore, our advice to policy makers
      is to use disaggregated models to better disentangle these contributions and to
      produce more reliable health spending forecasts. 

PMID- 24908171
TI  - How religious status shapes psychological well-being: cultural consonance as a
      measure of subcultural status among Brazilian Pentecostals.
AB  - Research on subjective social status has long recognized that individuals occupy
      multiple social hierarchies, with socioeconomic status (SES) being but one. The
      issue, as such, has been to identify culturally meaningful measures of social
      status. Through cognitive anthropological theory and methods, I show that it is
      possible to identify multiple cultural models of "status," and objectively
      measure an individual's level of adherence, or consonance, with each-effectively
      placing them within the multidimensional space of social hierarchies. Through a
      mixed qualitative and quantitative study of 118 Brazilian Pentecostals carried
      out from 2011 to 2012, I show that dominant and limitedly-distributed cultural
      models of status operate simultaneously and concurrently in the lives of those
      who hold them. Importantly, each marker of cultural status moderates the other's
      association with psychological well-being. I argue that the importance of a given
      social hierarchy is framed by cultural values. For Brazilian Pentecostals, their
      limitedly distributed model of religious status alters the influence of more
      dominant societal indicators on psychological well-being. The interaction between
      religious and secular lifestyle statuses on psychological health is stronger than
      the association of SES, effectively explaining 51% of the variance. This finding
      suggests that among some populations, limitedly distributed cultural models of
      status may be a dominant force in shaping measures of well-being. 

PMID- 24908172
TI  - Discussing race-related limitations of genomic testing for colon cancer risk:
      implications for education and counseling.
AB  - This study examines communication about limitations of genomic results
      interpretation for colon cancer risk during education and counseling of minority
      participants. As part of a larger study conducted from 2010 to 2012, participants
      recruited from a large primary care clinic were offered testing for a research
      panel of 3 genomic markers (single nucleotide polymorphisms or SNPs) for
      colorectal cancer risk. Genetic counselors conducted pre- and post-test sessions
      which included discussion of limitations of result interpretation due to the lack
      of racial/ethnic diversity in research populations from which risk data are
      derived. Sessions were audio-recorded, transcribed and thematically analyzed.
      Many participants did not respond directly to this limitation. Among the
      participants that responded directly to this race-related limitation, many
      responses were negative. However, a few participants connected the limited
      minority information about SNPs with the importance of their current research
      participation. Genetic counselor discussions of this limitation were biomedically
      focused with limited explanations for the lacking data. The communication process
      themes identified included: low immediacy (infrequent use of language directly
      involving a participant), verbal dominance (greater speaking ratio of the
      counselor to the patient) and wide variation in the degree of interactivity (or
      the amount of turn-taking during the discussion). Placed within the larger
      literature on patient-provider communication, these present results provide
      insight into the dynamics surrounding race-related educational content for
      genomic testing and other emerging technologies. Clinicians may be better able to
      engage patients in the use of new genomic technology by increasing their
      awareness of specific communication processes and patterns during education or
      counseling sessions. 

PMID- 24908173
TI  - Testing a discrete choice experiment including duration to value health states
      for large descriptive systems: addressing design and sampling issues.
AB  - There is interest in the use of discrete choice experiments that include a
      duration attribute (DCETTO) to generate health utility values, but questions
      remain on its feasibility in large health state descriptive systems. This study
      examines the stability of DCETTO to estimate health utility values from the five
      level EQ-5D, an instrument with depicts 3125 different health states. Between
      January and March 2011, we administered 120 DCETTO tasks based on the five-level
      EQ-5D to a total of 1799 respondents in the UK (each completed 15 DCETTO tasks on
      line). We compared models across different sample sizes and different total
      numbers of observations. We found the DCETTO coefficients were generally
      consistent, with high agreement between individual ordinal preferences and
      aggregate cardinal values. Keeping the DCE design and the total number of
      observations fixed, subsamples consisting of 10 tasks per respondent with an
      intermediate sized sample, and 15 tasks with a smaller sample provide similar
      results in comparison to the whole sample model. In conclusion, we find that the
      DCETTO is a feasible method for developing values for larger descriptive systems
      such as EQ-5D-5L, and find evidence supporting important design features for
      future valuation studies that use the DCETTO. 

PMID- 24908174
TI  - Human CNS immune senescence and neurodegeneration.
AB  - Microglial cells comprising the brain's immune system are essential for ensuring
      neuroprotection in the normal and pathological CNS. On the basis of
      histopathological observations in human brain, we believe that the ability of
      microglia to provide neuroprotection deteriorates as our brains get older and
      that such CNS immune senescence is a major factor contributing to the development
      of aging-related neurodegenerative diseases, notably Alzheimer's disease. The
      idea is consistent with the fact that immune senescence occurs naturally in the
      periphery, rendering the elderly people more susceptible to infections and
      cancers. There is an analogous situation in the brain, except that here the main
      impact comes down to diminished neuroprotection and resultant neurodegeneration. 

PMID- 24908175
TI  - Novel placental ultrasound assessment: potential role in pre-gestational diabetic
      pregnancy.
AB  - OBJECTIVES: Management of women with pre-gestational diabetes continues to be
      challenging for clinicians. This study aims to determine if 3D power Doppler
      (3DPD) analysis of placental volume and flow, and calculation of placental
      calcification using a novel software method, differ between pregnancies with type
      1 or type 2 diabetes and normal controls, and if there is a relationship between
      these ultrasound placental parameters and clinical measures in diabetics.
      METHODS: This was a prospective cohort study of 50 women with diabetes and 250
      controls (12-40 weeks gestation). 3DPD ultrasound was used to evaluate placental
      volume, vascularisation index (VI), flow index (FI) and vascularisation-flow
      index (VFI). Placental calcification was calculated by computer analysis. Results
      in diabetics were compared with control values, and correlated with early
      pregnancy HbA1c, Doppler results and placental histology. RESULTS: Placental
      calcification and volume increased with advancing gestation in pre-gestational
      diabetic placentae. Volume was also found to be significantly higher than in
      normal placentae. VI and VFI were significantly lower in diabetic pregnancies
      between 35 and 40 weeks gestation. A strong relationship was seen between a
      larger placental volume and both increasing umbilical artery pulsatility index
      and decreasing middle cerebral artery pulsatility index. FI was significantly
      lower in cases which had a booking HbA1c level >=6.5%. Ultrasound assessed
      placental calcification was reduced with a histology finding of delayed villous
      maturation. No other correlation with placental histology was found. CONCLUSIONS:
      This study shows a potential role for 3D placental evaluation, and computer
      analysis of calcification, in monitoring pre-gestational diabetic pregnancies.

PMID- 24908176
TI  - Using scalar products to refine the interpretative value of an orientation choice
      test.
AB  - Choice tests, which are often used to examine animal preferences, can be
      difficult to interpret when no clear choice has been made or when using very
      young animals which exclude test repetition. We present a new method to evaluate
      the behavior in a choice test based on the orientation of the animal and
      illustrate its use when facing those conditions. Using rat pups in an open field
      maze with a choice of odors, we obtained x,y coordinates of 2 markers (head and
      body center) using a video-tracking freeware. Two vectors were calculated: an
      animal orientation vector (body to head) and a perfect orientation vector (body
      to odor source). The angle between the 2 vectors in each frame was converted into
      a scalar product ranging from 1 (pup oriented directly towards the odor source)
      to -1 (facing the opposite direction). A mean scalar product was calculated for
      each odor source, with the difference between the 2 mean scalar products
      indicating degree of preference for an odor. The information provided by the mean
      scalar product difference (MSPD) could not be obtained from other measures, such
      as binary choice, velocity, or distance moved. The MSPD provides a single,
      noncategorical value for each animal to describe degree of preference in a choice
      test. This variable was more effective in differentiating animals, thus allowing
      a reduction in the number of animals or tests necessary to reach significance. 

PMID- 24908177
TI  - [Hypofractionated stereotactic radiotherapy of bone metastases].
AB  - Hypofractionated stereotactic radiotherapy can deliver high doses of bone
      metastases while sparing adjacent healthy tissue not only for a decompressive or
      analgesic purpose, but also to improve the local control of the irradiated
      region. Various phases I or II studies showed the feasibility of such an approach
      at the cost of limited toxicity, including during re-irradiation.
      Hypofractionated stereotactic radiotherapy to oligometastases may also improve
      the long-term control of metastatic disease. 

PMID- 24908178
TI  - The effectiveness and safety of rescue treatments in 108 patients with steroid
      refractory ulcerative colitis with sequential rescue therapies in a subgroup of
      patients.
AB  - BACKGROUND: Among patients with steroid-refractory ulcerative colitis (UC) in
      whom a first rescue therapy has failed, a second line salvage treatment can be
      considered to avoid colectomy. AIM: To evaluate the efficacy and safety of second
      or third line rescue therapy over a one-year period. METHODS: Response to single
      or sequential rescue treatments with infliximab (5mg/kg intravenously (iv) at
      week 0, 2, 6 and then every 8weeks), ciclosporin (iv 2mg/kg/daily and then oral
      5mg/kg/daily) or tacrolimus (0.05mg/kg divided in 2 doses) in steroid-refractory
      moderate to severe UC patients from 7 Swiss and 1 Serbian tertiary IBD centers
      was retrospectively studied. The primary endpoint was the one year colectomy
      rate. RESULTS: 60% of patients responded to the first rescue therapy, 10% went to
      colectomy and 30% non-responders were switched to a 2(nd) line rescue treatment.
      66% of patients responded to the 2(nd) line treatment whereas 34% failed, of
      which 15% went to colectomy and 19% received a 3(rd) line rescue treatment. Among
      those, 50% patients went to colectomy. Overall colectomy rate of the whole cohort
      was 18%. Steroid-free remission rate was 39%. The adverse event rates were 33%,
      37.5% and 30% for the first, second and third line treatment respectively.
      CONCLUSION: Our data show that medical intervention even with 2(nd) and 3(rd)
      rescue treatments decreased colectomy frequency within one year of follow up. A
      longer follow-up will be necessary to investigate whether sequential therapy will
      only postpone colectomy and what percentage of patients will remain in long-term
      remission.

PMID- 24908179
TI  - Acid violence in Cambodia: the human, medical and surgical implications.
AB  - INTRODUCTION: Acid violence is the deliberate use of acid to attack another human
      being. Such attacks leave a terrible human, medical and surgical legacy. This
      study, from one of the largest cohorts of acid attack victims to date, provides
      insights into Cambodia's unique demographics of such attacks, as well as the
      human cost and necessary surgical interventions. METHODS: A retrospective cohort
      consisting of all patients presenting to the Children's Surgical Centre, Phnom
      Penh with acid burns from 1 January 2000 to 1 January 2013 was identified and
      information retrieved from their hospital records. RESULTS: 254 patients were
      identified. Males and females were almost equally likely to be victims of an acid
      attack (48.4% and 51.6% respectively). There was no significant association
      between victim and assailant gender (p=0.475). The face (78.0%), neck (51.5%) and
      chest (49.0%) were the most frequently affected body areas. The median total
      surface body area affected by acid burns was 7.0%. The mortality rate from acid
      assault was 2.0%. Patients required an average of 2.0 operations, ranging from 0
      to 18. CONCLUSIONS: Acid violence in Cambodia has a complex demographic which is
      different to many other developing countries and requires more investigation.
      Tougher legislation is required to reduce the incidence of these horrific crimes.

PMID- 24908180
TI  - The pig as an experimental model for mid-dermal burns research.
AB  - This was a novel, prospective and interventional animal study designed to develop
      and evaluate a new infliction device for the experimental burn model. Four paired
      sets of contact burns measuring 36mm diameter were inflicted on the dorsum of an
      anesthetized pig using a stainless steel round bar heated up to 80-110 degrees C.
      The bar was applied using a push-pull force gauge designed to control 1kgf
      mechanical force applied to the skin for a period of 20s. The left dorsum was
      used for macroscopic observation and the right dorsum was used for
      histopathological evaluation. A total of eight burns were covered with moist
      saline dressings and given daily treatments of xylocaine (lidocaine HCl) gel.
      This procedure was followed for a period of 24 days. Full-thickness biopsies were
      obtained for histologic analysis to determine the extent of injury. Statistical
      analysis showed a high correlation between the exposure temperature and
      histopathological assessment. The results found the depth of injury to the
      collagen (Seg1) correlated with the temperature (Ti) at which the burns was
      inflicted, Seg1=0.038Ti-2.57 (r=0.973, P<0.05). Also, the histological studies
      show a high correlation between the depth of collagen denaturation in wounds and
      the exposure temperature, Seg1=0.0268Ti-0.165 (r=0.991, P<0.05). This model is
      useful to assess more closely the therapeutic agents used for wound healing in
      experimental burn wounds. 

PMID- 24908181
TI  - Immunohistochemical analysis of neuropeptides (protein gene product 9.5,
      substance P and calcitonin gene-related peptide) in hypertrophic burn scar with
      pain and itching.
AB  - BACKGROUND: Neuropeptides have been recently reported as having an important role
      in wound repair, and relief from pain and itching sensation. The aim of this
      study was to evaluate the effect of neuropeptides on the wound healing process in
      hypertrophic scar formation that accompanies severe pain and itching sensation.
      METHODS: We collected forty-three hypertrophic scar specimens from hypertrophic
      scar release and skin graft under general anesthesia. Immunohistochemical stains
      for protein gene product (PGP) 9.5, substance P (SP), and calcitonin gene-related
      peptide (CGRP) were performed. Pain and itching over the scar were recorded using
      verbal numerical rating scale (VNRS). RESULTS: In the epidermis, PGP 9.5, SP, and
      CGRP were significantly increased in hypertrophic scars compared with matched
      unburned skin. In the reticular dermis, SP and CGRP were significantly increased
      in hypertrophic scars compared with control. The pain and itching verbal
      numerical rating scale in scar group were significantly higher compared to
      control. In the papillary dermis, the PGP represented significant correlation
      with Itching P (correlation coefficient 0.698) and the SP represented significant
      correlation with pain N (correlation coefficient -0.671). In the reticular
      dermis, the SP represented significant correlation with pain N (correlation
      coefficient -0.614) and CGRP represented significant correlation with pain
      P/Itching P (correlation coefficient 0.801/0.611). CONCLUSIONS: Neuropeptides
      such as PGP 9.5, SP, and CGRP seem to affect scarring via sensory
      neurotransmission, it have a regulatory role for pain and itching sensation in
      hypertrophic scars.

PMID- 24908182
TI  - Role of CX3CL1 in the chemotactic migration of all-trans retinoic acid-treated
      acute promyelocytic leukemic cells toward apoptotic cells.
AB  - BACKGROUND: Phagocytic clearance of apoptotic neutrophils by tissue macrophages
      is a crucial component in the resolution phase of acute inflammation. However,
      the number of tissue macrophages is low and not likely to cope satisfactorily
      with the excess number of dying neutrophils. Although recent studies have
      reported that neutrophils are able to engulf apoptotic neutrophils, the
      mechanisms by which living neutrophils are attracted to apoptotic neutrophils are
      poorly defined. Increased amounts of CX3CL1 and microparticles (MPs) are rapidly
      released by apoptotic cells, and are involved in the chemoattraction of
      mononuclear phagocytes toward apoptotic cells. The current study investigated the
      role of CX3CL1 in the chemoattraction of all-trans retinoic acid (ATRA)-treated
      NB4 (ATRA-NB4) cells toward apoptotic cells. METHODS: Conditioning medium and MPs
      were harvested from apoptotic ATRA-NB4 cell cultures to determine their effects
      on living ATRA-NB4 cells by transmigration assay and adhesion assay. The cytokine
      levels in the conditioning medium were determined by enzyme-linked immunosorbent
      assay. Expression of CX3CR1 (a receptor of CX3CL1) on ATRA-NB4 cells was
      determined by flow cytometric analysis. RESULTS: ATRA-NB4 cells transmigrated
      toward the apoptotic ATRA-NB4 cells, and this chemoattraction was partially
      inhibited when the CX3CR1 on ATRA-NB4 cells was blocked by its specific antibody.
      Both exogenous CX3CL1 and MPs released by apoptotic ATRA-NB4 cells were able to
      enhance the chemoattraction of ATRA-NB4 cells toward apoptotic cells or the
      adhesion of ATRA-NB4 cells to endothelial cells. CX3CL1 was expressed on the
      surface of MPs, and blocking this CX3CL1 with its specific antibody was able to
      partially inhibit the chemoattractive property of MPs. CONCLUSION: CX3CL1, in
      either the free or MP form, is released rapidly by apoptotic ATRA-NB4 cells after
      induction of apoptosis to mediate the chemoattraction of living ATRA-NB4 cells
      toward apoptotic cells.

PMID- 24908183
TI  - Impact of ovarian preservation in women with endometrial cancer.
AB  - BACKGROUND: Bilateral salpingo-oophorectomy (BSO) is standardly performed in the
      treatment of endometrial cancer. The purpose of this study was to evaluate the
      impact of ovarian preservation on the outcome of patients with endometrial
      cancer. METHODS: A retrospective cohort study was performed using the 2000-2010
      database of endometrial cancer patients who were treated at Taipei Veterans
      General Hospital. Information regarding patient age, pathologic reports, and
      follow-up results was abstracted from medical records. RESULTS: Five hundred and
      twenty-nine patients were reviewed in this study. Mean age and follow-up duration
      were 55.7 +/- 11.4 years and 37.5 +/- 30.1 months, respectively. The median
      disease-free survival was 31.2 months (range 0.2-126.9 months). There were no
      significant differences in disease-free survival between stage I patients with
      ovarian preservation versus those with oophorectomy (p = 0.473). In a
      multivariate Cox model, ovarian preservation had no effect on disease-free
      survival [hazard ratio (HR) = 2.72; 95% confidence interval (CI), 0.48-15.59];
      however, it was not significantly related to stage and para-aortic lymph node
      involvement. CONCLUSION: Ovarian preservation may be considered in premenopausal
      women with early-stage low-risk endometrial cancer.

PMID- 24908184
TI  - Segmental pulmonary artery transection after blunt trauma.
AB  - We herein describe a patient with segmental pulmonary artery transection after
      blunt trauma, which was diagnosed preoperatively by computed tomography. Bolus
      tracking contrast-enhanced computed tomography clearly depicted both aortic and
      pulmonary vasculatures. A one-step examination quickly disclosed aortic damage
      and injury to significant visceral organs. To the best of our knowledge, our
      patient appeared to be a unique case of pulmonary segmental artery transection
      after blunt injury, which was preoperatively diagnosed by computed tomography.
      Ultimately, successful surgical repair of the pulmonary artery was performed. 

PMID- 24908185
TI  - The role of excess mass in the adaptation of children's gait.
AB  - The aim of this study was to determine differences in lower extremity joint
      powers at weight acceptance and propulsion in obese and non-obese children during
      two loading conditions. Gait analyses were conducted on 20 non-obese and 20 obese
      children (8-12years). The first testing session was completed in a normal
      (unloaded) condition; an additional 10% body mass (acute loading) was added
      during the second session. Peak lower extremity joint power (W) phases were
      identified at weight acceptance and propulsion. Obese children demonstrated
      greater joint powers than non-obese children, at both weight acceptance and
      propulsion. Likewise, all children produced larger joint powers during acute
      loading conditions than unloaded. When body mass is a covariate, significant main
      effects for loading conditions remained for the hip and knee during weight
      acceptance and the hip and ankle at propulsion; no group differences remained
      significant. Obese children produced greater power generation at the hip and
      ankle during unloaded conditions than non-obese children during acute conditions.
      Only the ankle had greater power generation after accounting for body mass. The
      findings suggest that obese children must increase muscular contraction force to
      maintain normal gait function. While increased joint powers necessary for normal
      gait could result in incidental muscle strengthening of obese children, this
      persistent increase in muscular force demand could result in musculoskeletal
      injury. 

PMID- 24908186
TI  - Construction of an efficient Escherichia coli whole-cell biocatalyst for D
      mannitol production.
AB  - Mannitol is a six carbon sugar alcohol that finds applications in the
      pharmaceutical and food industries. A novel Escherichia coli strain capable of
      converting D-glucose to D-mannitol has been constructed, wherein native mannitol
      1-phosphate dehydrogenase (MtlD) and codon-optimized Eimeria tenella mannitol-1
      phosphatase (M1Pase) have been overexpressed. Codon-optimized Pseudomonas
      stutzeri phosphite dehydrogenase (PtxD) was overexpressed for cofactor (NADH)
      regeneration with the concomitant oxidation of phosphite to phosphate. Whole-cell
      biotransformation using resting cells in a medium containing D-glucose and
      equimolar sodium phosphite resulted in d-mannitol yield of 87 mol%. Thus,
      production of an industrially relevant biochemical without using complex media
      components and elaborate process control mechanisms has been demonstrated.

PMID- 24908187
TI  - Diagnosis and early detection of CNS-SLE in MRL/lpr mice using peptide
      microarrays.
AB  - BACKGROUND: An accurate method that can diagnose and predict lupus and its
      neuropsychiatric manifestations is essential since currently there are no
      reliable methods. Autoantibodies to a varied panel of antigens in the body are
      characteristic of lupus. In this study we investigated whether serum autoantibody
      binding patterns on random-sequence peptide microarrays (immunosignaturing) can
      be used for diagnosing and predicting the onset of lupus and its central nervous
      system (CNS) manifestations. We also tested the techniques for identifying
      potentially pathogenic autoantibodies in CNS-Lupus. We used the well
      characterized MRL/lpr lupus animal model in two studies as a first step to
      develop and evaluate future studies in humans. RESULTS: In study one we
      identified possible diagnostic peptides for both lupus and altered behavior in
      the forced swim test. When comparing the results of study one to that of study
      two (carried out in a similar manner), we further identified potential peptides
      that may be diagnostic and predictive of both lupus and altered behavior in the
      forced swim test. We also characterized five potentially pathogenic brain
      reactive autoantibodies, as well as suggested possible brain targets.
      CONCLUSIONS: These results indicate that immunosignaturing could predict and
      diagnose lupus and its CNS manifestations. It can also be used to characterize
      pathogenic autoantibodies, which may help to better understand the underlying
      mechanisms of CNS-Lupus.

PMID- 24908188
TI  - Kangaroo Mother Care: A review of mothers''experiences at Bwaila hospital and
      Zomba Central hospital (Malawi).
AB  - BACKGROUND: Kangaroo Mother Care is an intervention that can help reduce neonatal
      mortality rate in Malawi but it has not been rolled out to all health facilities.
      Understanding the mothers' experience would help strategise when scaling-up this
      intervention. OBJECTIVE: to review experiences of mothers Kangaroo Mother Care at
      two hospitals of Bwaila and Zomba. DESIGN: quantitative, descriptive using open
      interviews. SETTING: two central hospitals in Malawi. PARTICIPANTS: 113 mothers
      that were in the Kangaroo Mother Care unit and those that had come for follow-up
      two weeks after discharge before the study took place. FINDINGS: mothers had high
      level of knowledge about the significant benefits of Kangaroo Mother Care but 84%
      were not aware of the services prior to their hospitalisation. 18.6% (n=19) were
      not counselled prior to KMC practice. Mothers preferred KMC to incubator care.
      There were factors affecting compliance and continuation of KMC, which were lack
      of support, culture, lack of assistance with skin-to-skin contact, multiple roles
      of the mother and stigma. KEY CONCLUSIONS: mothers had a positive attitude
      towards KMC once fully aware of its benefits. IMPLICATIONS FOR PRACTICE: there is
      need for awareness campaigns on KMC services, provision of counselling, support
      and assistance which can help motivate mothers and their families to comply with
      the guidelines of KMC services.

PMID- 24908189
TI  - Vaccination of domestic animals against tuberculosis: review of progress and
      contributions to the field of the TBSTEP project.
AB  - Tuberculosis either caused by Mycobacterium bovis or M. caprae is a significant
      burden to agricultural industries worldwide. Vaccination of domestic ruminant
      species such as cattle and goats constitutes a potential tool to support disease
      control. This review will discuss recent progress made to develop tuberculosis
      vaccines against domestic ruminants as well as approaches to differentiate
      vaccinated and infected animals (DIVA) and biomarker discovery studies.

PMID- 24908190
TI  - Simple synthesis of new carbon-11-labeled 1,2,4-triazolo[4,3-a]quinoxalin-1-one
      derivatives for PET imaging of A3 adenosine receptor.
AB  - The reference standards 4a-b, 6a-b, 7a-c, and desmethylated precursors 9a-b, 10a
      b, 8a-c were synthesized from 4-methoxyaniline, ethyl 2-chloro-acetoacetate and
      substituted benzene-1,2-diamines with 3, 5, 6 steps in 61-67%, 34-41%, 23-31%,
      and with 4, 6, 7 steps in 49-57%, 28-35%, 20-27% overall chemical yield,
      respectively. The target tracers [(11)C]4a-b, [(11)C]6a-b, [(11)C]7a-c were
      synthesized from their corresponding precursors with [(11)C]CH3OTf through O
      [(11)C]methylation and isolated by simplified SPE in 40-60% decay corrected
      radiochemical yields at EOB, with 185-370 GBq/MUmol specific activity at EOS.

PMID- 24908192
TI  - Computer aided detection of epidural masses on computed tomography scans.
AB  - The widespread use of CT imaging and the critical importance of early detection
      of epidural masses of the spinal canal generate a scenario ideal for the
      implementation of a computer-aided detection (CAD) system. Epidural masses can
      lead to paralysis, incontinence and loss of neurological function if not promptly
      detected. We present, to our knowledge, the first CAD system to detect epidural
      masses on CT scans. In this paper, spatially constrained Gaussian mixture model
      (GMM) and supervoxel-based method are proposed for epidural mass detection. The
      detection is performed on the Gaussian level or the supervoxel level rather than
      the voxel level. Cross-validation on 40 patients with epidural masses on body CT
      showed that the supervoxel-based method yielded a significant improvement of
      performance (82% at 3 false positives per patient) over the spatially constrained
      GMM method (55% at 3 false positives per patient). 

PMID- 24908191
TI  - International multicenter experience with an over-the-scope clipping device for
      endoscopic management of GI defects (with video).
AB  - BACKGROUND: The over-the-scope clip (OTSC) provides more durable and full
      thickness closure as compared with standard clips. Only case reports and small
      case series have reported on outcomes of OTSC closure of GI defects. OBJECTIVE:
      To describe a large, multicenter experience with OTSCs for the management of GI
      defects. Secondary goals were to determine success rate by type of defect and
      type of therapy and to determine predictors of treatment outcomes. DESIGN:
      Multicenter, retrospective study. SETTING: Multiple, international, academic
      centers. PATIENTS: Consecutive patients who underwent attempted OTSC placement
      for GI defects, either as a primary or as a rescue therapy. INTERVENTIONS: OTSC
      placement to attempt closure of GI defects. MAIN OUTCOME MEASUREMENTS: Long-term
      success of the procedure. RESULTS: A total of 188 patients (108 fistulae, 48
      perforations, 32 leaks) were included. Long-term success was achieved in 60.2% of
      patients during a median follow-up of 146 days. Rate of successful closure of
      perforations (90%) and leaks (73.3%) was significantly higher than that of
      fistulae (42.9%) (P < .05). Long-term success was significantly higher when OTSCs
      were applied as primary therapy (primary 69.1% vs rescue 46.9%; P = .004). On
      multivariate analysis, patients who had OTSC placement for perforations and leaks
      had significantly higher long-term success compared with those who had fistulae
      (OR 51.4 and 8.36, respectively). LIMITATIONS: Retrospective design and multiple
      operators with variable expertise with the OTSC device. CONCLUSION: OTSC is safe
      and effective therapy for closure of GI defects. Clinical success is best
      achieved in patients undergoing closure of perforations or leaks when OTSC is
      used for primary or rescue therapy. Type of defect is the best predictor of
      successful long-term closure.

PMID- 24908193
TI  - Real-scale 3D models of the scoliotic spine from biplanar radiography without
      calibration objects.
AB  - This paper presents a new method for modelling the spines of subjects and making
      accurate 3D measurements using standard radiologic systems without requiring
      calibration objects. The method makes use of the focal distance and statistical
      models for estimating the geometrical parameters of the system. A dataset of 32
      subjects was used to assess this method. The results show small errors for the
      main clinical indices, such as an RMS error of 0.49 degrees  for the Cobb angle,
      0.50 degrees  for kyphosis, 0.38 degrees  for lordosis, and 2.62mm for the spinal
      length. This method is the first to achieve this level of accuracy without
      requiring the use of calibration objects when acquiring radiographs. We conclude
      that the proposed method allows for the evaluation of scoliosis with a much
      simpler setup than currently available methods. 

PMID- 24908194
TI  - Treatment of prolonged convulsive seizures in children; a single centre,
      retrospective, observational study.
AB  - OBJECTIVES: To evaluate treatment of children with Prolonged Convulsive Seizures
      (PCS) at the University Medical Centre Groningen (UMCG). MATERIAL AND METHODS:
      PCS were identified from an UMCG database of children with epilepsy aged <18
      years who had their first (a)febrile seizure between 2000 and 2010. PCS were
      included if they lasted >=10 min and occurred between January 2000 and October
      2012 in children aged >1 month. Order, timing, and location of treatment were
      analysed. Treatment of PCS before and after 2005 was compared with
      recommendations from a Dutch 2005 treatment guideline for Convulsive Status
      Epilepticus (CSE) in children aged >1 month. RESULTS: 269 PCS occurring in 102
      children were included (53.9% male, median age 2.8 years; range 0.1-13.7 years).
      Seventy episodes concerned a first PCS. Most first and subsequent PCS started
      outside the hospital (78.6% and 82.4%, respectively) and lasted 10-30 min (42.4%
      and 51.4%, respectively). Cessation occurred after two administrations of any
      therapy in first (median, range 0-7) and subsequent PCS (median, range 0-10).
      First treatment choice was rectal diazepam in first (59.6%) and subsequent
      (43.9%) PCS, but since 2006 a trend towards buccal midazolam was observed in
      subsequent PCS. Clonazepam was frequently used as second treatment choice in
      first (43.8%) and subsequent (27.3%) PCS, although not mentioned in the
      guideline. CONCLUSION: In our study cohort rectal diazepam is still first choice
      in the management of PCS despite proven superior efficacy of buccal midazolam.
      Clonazepam is frequently used although it is not formally recommended in a Dutch
      guideline.

PMID- 24908195
TI  - Unilateral deep brain stimulation of the pedunculopontine tegmental nucleus in
      idiopathic Parkinson's disease: effects on gait initiation and performance.
AB  - The pedunculopontine tegmental nucleus (PPTg) is a component of the locomotor
      mesencephalic area. In recent years it has been considered a new surgical site
      for deep brain stimulation (DBS) in movement disorders. Here, using objective
      kinematic and spatio-temporal gait analysis, we report the impact of low
      frequency (40 Hz) unilateral PPTg DBS in ten patients suffering from idiopathic
      Parkinson's disease with drug-resistant gait and axial disabilities. Patients
      were studied for gait initiation (GI) and steady-state level walking (LW) under
      residual drug therapy. In the LW study, a straight walking task was employed.
      Patients were compared with healthy age-matched controls. The analysis revealed
      that GI, cadence, stride length and left pelvic tilt range of motion (ROM)
      improved under stimulation. The duration of the S1 and S2 sub-phases of the
      anticipatory postural adjustment phase of GI was not affected by stimulation,
      however a significant improvement was observed in the S1 sub-phase in both the
      backward shift of centre of pressure and peak velocity. Speed during the swing
      phase, step width, stance duration, right pelvic tilt ROM phase, right and left
      hip flexion-extension ROM, and right and left knee ROM were not modified.
      Overall, the results show that unilateral PPTg DBS may affect GI and specific
      spatio-temporal and kinematic parameters during unconstrained walking on a
      straight trajectory, thus providing further support to the importance of the PPTg
      in the modulation of gait in neurodegenerative disorders.

PMID- 24908196
TI  - Age estimation in U-20 football players using 3.0 tesla MRI of the clavicle.
AB  - BACKGROUND: To guarantee equal chances for participants in U-20 football
      tournaments, it seems desirable to verify the ages given by players with
      questionable dates of birth. OBJECTIVE: To study the potential use of 3.0 tesla
      MRI of the clavicle in estimating the ages of U-20 football players. METHODS: The
      ossification stage of the medial clavicular epiphyses was evaluated prospectively
      in 152 male footballers in the age group from 18 to 22 years using 3.0 tesla MRI.
      RESULTS: Average age increased with any higher degree of fusion. The only
      footballer with full ossification of the medial clavicular epiphyseal plate was
      21.2 years old. CONCLUSIONS: The presence of a fully ossified clavicular
      epiphyseal plate appears to provide evidence of completion of the 20th year of
      life. The results of the pilot study need to be verified in a larger number of
      cases.

PMID- 24908197
TI  - Importance of the reversed halo sign for the diagnosis of angioinvasive pulmonary
      aspergillosis.

PMID- 24908198
TI  - Morphological and molecular characterization of three new Azadinium species
      (Amphidomataceae, dinophyceae) from the Irminger sea.
AB  - Some species of the planktonic dinoflagellate genus Azadinium produce
      azaspiracids (AZAs), a group of lipophilic phycotoxins causing human poisoning
      after mussel consumption. We describe three new species from the North Atlantic,
      all of which shared the same Kofoidean plate pattern characteristic for
      Azadinium: Po, cp, X, 4', 3a, 6", 6C, 5S, 6'", 2"". Azadinium trinitatum sp. nov.
      was mainly characterized by the presence of an antapical spine and by the
      position of the ventral pore at the left distal end of the pore plate in a cavity
      of plate 1'. Azadinium cuneatum sp. nov. had a conspicuously formed first apical
      plate, which was asymmetrically elongated and tapered on its left lateral side
      with a ventral pore located at the tip of this elongated 1' plate. Azadinium
      concinnum sp. nov. was of particular small size (< 10MUm) and characterized by an
      anteriorly elongated anterior sulcal plate and by large and symmetric precingular
      plates. The ventral pore was located inside the apical pore plate on the cells'
      right lateral side. Molecular phylogenetics as inferred from concatenated SSU
      rRNA, ITS, and LSU rRNA sequence data supported the distinctiveness of the three
      new species. None of the new species produced any known AZAs in measurable
      amounts.

PMID- 24908199
TI  - Fast water concentration mapping to normalize (1)H MR spectroscopic imaging.
AB  - OBJECT: To propose a fast and robust acquisition and post-processing pipeline
      that is time-compatible with clinical explorations to obtain a proton density
      (rho) map used as a reference for metabolic map normalization. This allows inter
      subject and inter-group comparisons of magnetic resonance spectroscopic imaging
      (MRSI) data and longitudinal follow-up for single subjects. MATERIALS AND
      METHODS: A multi-echo T 2 (*) mapping sequence, the XEP sequence for B 1 (+) 
      mapping and Driven Equilibrium Single Pulse Observation of T 1-an optimized
      variable flip angle method for T 1 mapping used for both B 1 (-) -mapping and M 0
      calculation-were used to determine correction factors leading to quantitative
      water proton density maps at 3T. Normalized metabolite maps were obtained on a
      phantom and nine healthy volunteers. To show the potential use of this technique
      at the individual level, we also explored one patient with low-grade glioma.
      RESULTS: Accurate rho maps were obtained both on phantom and volunteers. After
      signal normalization with the generated rho maps, metabolic concentrations
      determined by the present method differed from theory by <7 % in the phantom and
      were in agreement with data from the literature for the healthy controls. Using
      these normalized metabolic values, it was possible to demonstrate in the patient
      with brain glioma, metabolic abnormalities in normalized N-acetyl aspartate,
      choline and creatine levels; illustrating the potential for direct use of this
      technique in clinical studies. CONCLUSION: The proposed combination of sequences
      provides a robust rho map that can be used to normalize metabolic maps in
      clinical MRSI studies.

PMID- 24908201
TI  - Comparison of frequency and severity of longitudinal stent deformation among
      various drug-eluting stents: an intravascular ultrasound study.
AB  - BACKGROUND: Longitudinal stent deformation (LSD) in drug-eluting stents (DES) has
      been described as a disruption of stent structure. This study aimed to compare
      first- versus second-generation DES with respect to their actual stent length
      post deployment. METHODS: A total of 617 DES for de novo coronary lesions in 552
      patients were analyzed. Intravascular ultrasound (IVUS) was utilized to compare
      the degree and rate of LSD among six different DES types. IVUS-measured stent
      length was compared to the labeled length for calculation of absolute difference
      in stent length and relative absolute difference (absolute difference divided by
      the labeled length). RESULTS: The baseline characteristics were comparable
      between groups, except for higher calcification in the sirolimus-eluting stent
      (SES) group (p=0.037). The absolute and relative difference in length showed the
      lowest degree in the SES group and the highest degree in the Endeavor zotarolimus
      eluting stent group (p=0.085 and 0.078, respectively). The percentage of more
      than 5% relative absolute difference was the lowest in the SES group compared to
      the other groups (p=0.018). However, the percentage of significant (>15%)
      relative absolute difference was similar among groups (p=0.99). In multivariate
      linear regression analysis, labeled stent length and stent diameter, but not
      stent type, were identified as independent correlates to the absolute and
      relative difference in the actual stent length post-deployment. CONCLUSION: This
      IVUS analysis confirms that among second-generation DES, there is overall similar
      frequency and severity of LSD when deploying in common coronary lesions.

PMID- 24908200
TI  - Intravenous (-)-epicatechin reduces myocardial ischemic injury by protecting
      mitochondrial function.
AB  - BACKGROUND: Targeting the mitochondria during ischemia/reperfusion (IR) can
      confer cardioprotection leading to improved clinical outcomes. The
      cardioprotective potential of (-)-epicatechin (EPI) during IR via modulation of
      mitochondrial function was evaluated. METHODS AND RESULTS: Ischemia was induced
      in rats via a 45 min occlusion of the left anterior descending coronary artery
      followed by 1 h, 48 h, or 3 week reperfusion. EPI (10 mg/kg) was administered IV
      15 min prior to reperfusion for the single dose group and again 12 h later for
      the double dose group. Controls received water. Experiments also utilized
      cultured neonatal rat ventricular myocytes (NRVM) and myoblasts. A single dose of
      EPI reduced infarct size by 27% at 48 h and 28% at 3 week. Double dose treatment
      further decreased infarct size by 80% at 48 h, and 52% by 3 weeks. The protective
      effect of EPI on mitochondrial function was evident after 1h of reperfusion when
      mitochondria demonstrated less respiratory inhibition, lower mitochondrial Ca2+
      load, and a preserved pool of NADH that correlated with higher tissue ATP levels.
      Mechanistic studies in NRVM revealed that EPI acutely stimulated maximal rates of
      respiration, an effect that was blocked by inhibitors of the mitochondrial
      pyruvate carrier, nitric oxide synthase, or soluble guanylyl cyclase. In
      myoblasts, knockdown of components of the mitochondrial pyruvate carrier blocked
      EPI-induced respiratory stimulation. CONCLUSIONS: IV EPI confers cardioprotection
      via preservation of mitochondrial function potentially through enhanced substrate
      provision. These provocative results document a novel mechanism of a natural
      product with potential clinical utility.

PMID- 24908202
TI  - Depressive symptoms associated with poor health-related quality of life in adults
      with strabismus.

PMID- 24908204
TI  - Single nucleotide polymorphisms at the PRR3, ABCF1, and GNL1 genes in the HLA
      class I region are associated with Graves' ophthalmopathy in a gender-dependent
      manner.
AB  - OBJECTIVE: To investigate whether a conserved HLA class I region influenced the
      development of Graves' ophthalmopathy (GO) in patients with Graves' disease (GD)
      in a Taiwan-Chinese population. DESIGN: Case-control study. PARTICIPANTS: Four
      hundred sixty-eight Taiwan-Chinese patients with GD; 200 of these patients had
      GO, whereas 268 patients did not. METHODS: Five single nucleotide polymorphisms
      (SNPs) between the HLA-A and HLA-C loci were genotyped. MAIN OUTCOME MEASURES:
      The Mann-Whitney U test and chi-square test with Bonferroni correction were used.
      The odds ratios (ORs) were estimated by applying unconditional logistic
      regression with a 95% confidence intervals (CIs). RESULTS: Strong gender effects
      on the distribution of the SNPs were apparent: male GD patients carrying an A
      allele at rs2074503 in the PRR3 gene tended to avoid demonstrating GO (P = 0.008;
      OR, 0.450; 95% CI, 0.248-0.819), whereas female patients tended to show GO (P =
      0.01; OR, 1.486; 95% CI, 1.098-2.012). In addition, only the female GD patients
      with a T allele at rs1264439 in the ABCF-1 gene tended to demonstrate GO (P =
      0.005; OR, 1.539; 95% CI, 1.139-2.081). Analysis of the haplotype blocks of the
      SNPs rs2074505 (GNL1) and rs2074503 (PRR3) showed that haplotype HA1 was
      underrepresented in male GO patients (P = 0.004; OR, 0.418; 95% CI, 0.228-0.767),
      whereas HA-4 was underrepresented in female GO patients (P = 0.007; OR, 0.660;
      95% CI, 0.490-0.895). CONCLUSIONS: The results suggested that SNPs at PRR3 and
      ABCF1 genes and the haplotype composed by SNPs at GNL1 and PRR3 between the HLA-A
      and HLA-C genes tended to predict GO in a gender-dependent manner in patients
      with GD in Taiwan.

PMID- 24908203
TI  - Medically reversible limbal stem cell disease: clinical features and management
      strategies.
AB  - PURPOSE: To describe the clinical features and management strategies in patients
      whose limbal stem cell (LSC) disease reversed with medical therapy. DESIGN:
      Retrospective case series. PARTICIPANTS: Twenty-two eyes of 15 patients seen at 3
      tertiary referral centers between 2007 and 2011 with 3 months or more of follow
      up. METHODS: Medical records of patients with medically reversible LSC disease
      were reviewed. Demographic data, causes, location and duration of disease, and
      medical inventions were analyzed. MAIN OUTCOME MEASURES: Primary outcomes
      assessed included resolution of signs of LSC disease and improvement in visual
      acuity. RESULTS: Causes of the LSC disease included contact lens wear only (13
      eyes), contact lens wear in the setting of ocular rosacea (3 eyes), benzalkonium
      chloride toxicity (2 eyes), and idiopathic (4 eyes). Ophthalmologic findings
      included loss of limbal architecture, a whorl-like epitheliopathy, or an opaque
      epithelium arising from the limbus with late fluorescein staining. The superior
      limbus was the most common site of involvement (95%). The corneal epithelial
      phenotype returned to normal with only conservative measures, including
      lubrication and discontinuing contact lens wear in 4 patients (4 eyes), whereas
      in 11 patients (18 eyes), additional interventions were required after at least 3
      months of conservative therapy. Medical interventions included topical
      corticosteroids, topical cyclosporine, topical vitamin A, oral doxycycline,
      punctal occlusion, or a combination thereof. All eyes achieved a stable ocular
      surface over a mean follow-up of 15 months (range, 4-60 months). Visual acuity
      improved from a mean of 20/42 to 20/26 (P < 0.0184). CONCLUSIONS: Disturbances to
      the LSC function, niche, or both may be reversible with medical therapy. These
      cases, which represent a subset of patients with LSC deficiency, may be
      considered to have LSC niche dysfunction.

PMID- 24908206
TI  - Choroidal thickness in patients with diabetes and microalbuminuria.

PMID- 24908207
TI  - Myoclonus of the serratus anterior muscle after posterolateral thoracotomy.

PMID- 24908208
TI  - Risk factors for dementia in highly educated elderly people in Tianjin, China.
AB  - BACKGROUND: Low education level has been thought an important and specific risk
      factor for dementia. Therefore, we surveyed dementia in a highly educated
      population in Tianjin, China. METHODS: In total, 1324 old people (aged 55 years
      and over) in three cluster samples from university communities in Tianjin
      responded to our survey. Data from psychological tests and dementia
      questionnaires were analyzed. RESULTS: The prevalence of all-cause dementia,
      Alzheimer's disease (AD), and vascular dementia (VD) was 4.98%, 2.11%, and 2.27%,
      respectively. A history of stroke (OR=6.036), lack of fruit (OR=5.489), early
      parental death (OR=3.102), household financial management (OR=2.638), a history
      of cardiovascular disease (OR=2.434), a history of hypertension (OR=2.042),
      physical exercise (OR=2.556), were significantly associated with dementia in a
      single-factor analysis. Four independent variables were entered in a regression
      equation: early parental death (OR=6.417), lack of fruit in the diet (OR=3.919),
      personal stroke history (OR=3.901), and lack of physical exercise (OR=2.220).
      CONCLUSION: The prevalence of dementia was lower in highly educated elderly
      people in universities in Tianjin than in the general population. Risk factors
      for dementia included disease history, living habits, and early parental death,
      so corresponding interventions are required.

PMID- 24908209
TI  - Concomitant use of stereoelectroencephalography (SEEG) and
      magnetoencephalographic (MEG) in the surgical treatment of refractory focal
      epilepsy.

PMID- 24908210
TI  - Influence of smoking status at time of surgery for herniated lumbar disk on
      postoperative pain and health-related quality of life.
AB  - BACKGROUND: It is well established that smoking has a myriad of negative effects
      on varies aspects of bodily health. The aim of this study was to examine the
      effects of the smoking status at time of surgery on the postoperative subjective
      pain course and health related quality of life (HRQoL) until 1 year after surgery
      for lumbar disc herniation (LDH). METHOD: This prospective cohort study included
      patients >=18 and <=90 years of age with a symptomatic and radiological verified
      LDH. The current smoking patient collective (smoking 1 or more cigarettes a day)
      was compared with the nonsmoking collective (previous smokers without cigarette
      consumption for >2 months and never smokers) in respect of subjective pain
      sensation (measured with the visual analogue scale (VAS)) and HRQoL using the
      short-form (SF-12) questionnaire preoperatively, before discharge, as well as
      after 4 weeks and 1 year postoperatively. The primary outcome measures were the 1
      year SF-12 scores (MCS and PCS) categorized into responders and non-responders.
      RESULTS: A total of 102 patients were enrolled in the study. Thirty-eight
      patients were current smokers (37.2%), whereas 43 (42.2%) and 21 (20.6%) patients
      were never-smokers and previous smokers, respectively. Four weeks and one year
      after surgery, both smokers and nonsmokers reported increase in the HRQoL as
      compared to preoperative values - the MCS increased more than the PCS. From a
      univariate and multivariate perspective, smoking status at time of surgery did
      not predict responder status. CONCLUSIONS: The present study results could not
      confirm the hypothesis that smoking at time of surgery was associated with worse
      outcome after surgery for LDH.

PMID- 24908211
TI  - Hearing loss and Chiari malformation: a clinical pearl.

PMID- 24908212
TI  - Operative management of patients with radiosurgery-related trigeminal neuralgia:
      analysis of the surgical morbidity and pain outcome.
AB  - OBJECT: Trigeminal neuralgia (TGN) occurring after radiosurgical treatment of
      cerebellopontine or petroclival tumors may be very difficult to control. Our aim
      was to determine the efficacy of neurosurgical treatment in regards to pain
      control and to evaluate the procedure-related complication and morbidity rates.
      METHODS: Retrospective study of a series of operated patients with radiosurgery
      induced TGN. The primary goal of the surgery was to inspect and decompress the
      trigeminal nerve; the second goal was to remove the tumor remnant completely, if
      safely feasible. The main outcome measures were pain control, time to onset of
      pain relief and its duration, occurrence of new neurological deficits or
      worsening of the existing one and completeness of tumor removal. RESULTS: The
      four patients met the inclusion criteria: 2 with vestibular schwannomas, 1 with
      petroclival meningioma and 1 with an epidermoid. TGN occurred 12-60 months after
      radiosurgery (mean 39 months). At presentation the pain attacks occurred multiple
      timesdaily and lasted from a few seconds to 2-3min. The Complete tumor removal
      via the retrosigmoid approach was achieved in all cases. There were no major
      operative complications or persistent morbidity, besides one patient with
      trochlear nerve palsy. All patients experienced immediate pain relief after
      surgery. At follow-up (median duration - 42.5 months) the three patients reported
      complete pain resolution. One patient had occasional slight pain but did not need
      any medications. CONCLUSION: Surgery is safe and effective treatment option of
      patients with intractable radiosurgery-induced TGN. It leads to excellent pain
      control and is curative in regards to the neoplastic disease.

PMID- 24908213
TI  - 4-T fMRI of the motor and sensory cortices in patients with polymicrogyria and
      epilepsy.
AB  - OBJECTIVE: Malformations of cortical development (MCD) are an increasingly
      recognized cause of medically intractable epilepsy. We assessed the role of fMRI
      in evaluating the motor and somatosensory cortices, as well as if there is
      possible reorganization of these vital areas in patients with polymicrogyria.
      METHODS: We included 2 patients with polymicrogyria and epilepsy. Somatosensory
      and motor cortices were assessed with a 4T fMRI. These findings were compared
      with direct cortical stimulation. RESULTS: Localization of the sensorimotor
      cortices was adequately identified by fMRI. These vital areas did not reorganize
      outside the malformation of cortical development. CONCLUSION: fMRI is a tool that
      can allow identification of these vital areas of the brain in a non-invasive
      manner. PRACTICE IMPLICATIONS: Adequate localization of the sensorimotor cortices
      is important for optimal patient selection, surgical strategy, and to determine
      the maximal extent of the resection. The clinical implications for such
      understanding are not limited to it; these findings should help researchers
      understand more of the neurobiology of MCDs and even possibly clues to the
      mechanisms of epileptogenesis associated with such malformations.

PMID- 24908214
TI  - Occlusion of canine aneurysms using microporous self-expanding stent grafts: long
      term follow-up.
AB  - PURPOSE: The treatment of large or giant cerebral aneurysms by surgical and/or
      endovascular techniques is difficult and poses relatively high risks. Therefore,
      a microporous self-expanding (hybrid) stent graft composed of a thin, expandable,
      segmented polyurethane (SPU) membrane with micropores and a drug-delivery system
      was developed. MATERIALS AND METHODS: A commercially available, self-expanding
      carotid stent was covered with a thin microporous SPU membrane fabricated by the
      dip-coating method and the excimer laser ablation technique, with an intraluminal
      coating of argatroban. Experimentally fabricated lateral-wall aneurysms in canine
      carotid arteries using venous pouches were occluded with the hybrid stent graft
      (bale-shaped pore density of 23.6%) on one side and a bare-metal stent on the
      other side without systemic antiplatelet therapy. RESULTS: Angiography at 1, 6,
      and 12 months of stenting revealed that all arteries were patent without marked
      stenosis without systemic antiplatelet therapy. All aneurysms treated with hybrid
      stent grafts remained occluded throughout the 12-month period, while among those
      treated by bare-metal stents, 2 of 3 aneurysms were occluded at 6 months (67%)
      and only 1 of 3 aneurysms were occluded at 12 months (33%). Histology revealed
      that the novel hybrid stent graft had less intimal hyperplasia than the bare
      metal stent. The hybrid stent graft was useful for the successful occlusion of
      these canine carotid aneurysms, even at 12 months. CONCLUSIONS: The novel hybrid
      stent grafts are expected to overcome the disadvantages of fully covered stent
      grafts and simple bare-metal stents, while combining both their merits, and
      appear to be useful in the treatment of large or giant cerebral aneurysms.

PMID- 24908215
TI  - Surgical outcome of primary clipping for anterior circulation aneurysms of size 2
      centimeters or larger.
AB  - BACKGROUND: Aneurysms of the anterior circulation larger than 2cm have a complex
      relationship to the anterior skull base, requiring a multi-modality management
      approach. This retrospective study of 54 patients with such aneurysms who
      underwent clipping between 2001 and 2012 analyzes clinical and surgical data,
      aneurysm characteristics and correlates them with respect to the Glasgow outcome
      score at follow-up and immediate post-operative clinical status. METHODS:
      Patients with an outcome score of 5 or 4 were categorized as "good", while those
      with score 3-1 were "poor". Fisher's exact test and paired T-test (p<0.5) were
      used to test statistical significance for discrete and continuous variables
      respectively. RESULTS: 44 (81.4%) patients had a good outcome. Patients with non
      ophthalmic/paraclinoid aneurysms had significantly lower incidence of adverse
      intra-operative events (p=0.035). Patients older than 50 years (p=0.045), with
      adverse intra-operative events (p=0.015) and post-operative infarction (p<0.001)
      had a poor outcome compared to those younger than 50 years age and those without
      adverse intra-operative events or infarctions. The grouped age variable had
      maximum influence on patient outcome. Location and size of aneurysm did not have
      an overall impact on surgical outcome. There were 4 mortalities. CONCLUSIONS:
      Primary clipping of proximal non-cavernous aneurysms on the internal carotid
      artery is associated with adverse intra-operative events. A multi-modality
      treatment approach in these aneurysms should be individualized, more so in
      patients older than 50 years.

PMID- 24908216
TI  - Delayed cervical epidural hematoma after intravenous thrombolysis for acute
      ischemic stroke: case report and review of literature.

PMID- 24908217
TI  - The rCBV ratio on perfusion-weighted imaging reveals the extent of blood flow on
      conventional angiography after acute ischemic stroke.
AB  - OBJECTIVE: In this study, we evaluated the relationship between the rCBV
      (regional cerebral blood flow volume) ratio on perfusion-weighted imaging (PWI)
      and the extent of collateral flow on conventional angiography. METHODS: We
      recruited 98 patients with AIS (within 24h after ischemic events). All the
      patients were evaluated by MRI, including PWI and diffusion-weighted imaging
      (DWI), and underwent digital subtraction angiography (DSA) of the brain. We
      hypothesized that the rCBV ratio on PWI could reveal the extent of the blood flow
      and predict early neurological deterioration (END) within 7 days after AIS.
      RESULTS: The rCBV ratio on PWI was significantly correlated with its extent on
      DSA (p<0.01). During the observation period, 24 patients (24.5%) experienced END.
      The univariate analysis revealed that severe neurological deficit at admission
      (p<0.01), the volume of the ischemic lesion on DWI (p<0.01), poor blood flow on
      DSA (p<0.01), the presence of DPM (p=0.05) and a low rCBV ratio on PWI (p<0.01)
      were related to END occurrence. The multivariate analysis showed that the
      presence of a low rCBV ratio on PWI was independently significant as a correlate
      of END (OR, 5.64; 95% CI, 1.68-18.90; p<0.01). CONCLUSION: This study shows that
      the rCBV ratio on PWI may be a useful tool to reveal the status of blood flow
      after AIS. Moreover, the extent of collateral flow may be an important parameter
      that subtly influences the fate of DPM in AIS.

PMID- 24908218
TI  - A review of modifying factors affecting usage of diagnostic rating scales in
      concussion management.
AB  - Sport-related concussion has gained increasing recognition as a result of recent
      legislation, public health initiatives and media coverage. Moreover, there have
      been substantial paradigm shifts in the management of concussion. This article
      will discuss the variables that affect the use of diagnostic rating scales such
      as ImPACT and SCAT in the current management of concussed individuals.
      Specifically, patient-specific modifying factors affecting test interpretation,
      including age, gender, fitness level, psychiatric conditions, learning disorders
      and other components of medical history will be addressed, as well as
      methodological concerns with baseline testing. 

PMID- 24908219
TI  - Hemifacial spasm and trigeminal neuralgia in Chiari's I malformation with
      hydrocephalus: case report and literature review.
AB  - Chiari's I malformation with hydrocephalus is commonly seen in clinical
      experience. Trigeminal neuralgia (TN) and hemifacial spasm (HFS) are most
      commonly related to vascular compression of the root entry/enter zone (REZ).
      Until now, TN and HFS associated with hydrocephalus caused by Chiari's
      malformation have not been reported. The patient was a 24-year old male with left
      HFS and ipsilateral TN. Arnold-Chiari's I malformation with hydrocephalus and
      platybasia were found in magnetic resonance imaging (MRI) of brain. We underwent
      a programmable ventriculoperitoneal shunt with complete resolution of all
      symptoms. This is the first report of one case only presenting as coexistent
      ipsilateral TN and HFS secondary to Chiari's I malformation with hydrocephalus. 

PMID- 24908220
TI  - Early decompressive surgery after combined intra-venous thrombolysis and
      endovascular stroke treatment.
AB  - BACKGROUND AND PURPOSE: The prognosis of malignant middle cerebral artery
      infarctions (MCA) is poor. The poor prognosis is attributable to the severe
      cerebral edema that causes a brain herniation and death. Decompressive surgery
      reduces mortality and may further improve patient outcomes. However, the safety
      and effectiveness of decompressive surgery in patients who underwent combined
      intravenous (IV) thrombolysis and endovascular stroke treatment are not certain.
      Moreover, the evidence on the timing of decompressive surgery is lacking.
      METHODS: The purpose of the open, prospective and non-randomized study was to
      compare the outcome and complication rates of patients with malignant MCA strokes
      who underwent early decompressive surgery after combined intravenous thrombolysis
      and endovascular treatment with those of decompressive surgery patients without
      prior recanalization treatment strategy. All patients underwent decompressive
      surgery within 24h of symptom onset. RESULTS: Thirty patients were included in
      the study. Twelve of the 30 patients were treated with combined IV thrombolysis
      and endovascular approach and 18 patients received standard treatment. The
      proportion of patients with a modified Rankin score <=3 at the sixth month follow
      up was 33% in the standard group and 44% in the combined treatment group
      (p=0.712). Mortality, and major and minor complications including symptomatic
      intracerebral hemorrhage after decompressive surgery did not differ between the
      two groups (p>0.05). CONCLUSION: Early decompressive surgery can be safely
      performed in patients who received combined IV thrombolysis and endovascular
      treatment and there was no difference in outcome of these patients compared with
      patients who did receive the standard medical treatment before early
      decompressive surgery.

PMID- 24908221
TI  - Infection rate of emergency bolt-kit vs. non-emergency conventional implanted
      silver bearing external ventricular drainage catheters.
AB  - BACKGROUND: Bolt-kit systems are increasingly used as an alternative to
      conventional external cerebrospinal fluid (CSF) drainage systems. Since 2009 we
      regularly utilize bolt-kit external ventricular drainage (EVD) systems with
      silver-bearing catheters inserted manually with a hand drill and skull screws for
      emergency ventriculostomy. For non-emergency situations, we use conventional
      ventriculostomy with subcutaneous tunneled silver-bearing catheters, performed in
      the operating room with a pneumatic drill. This retrospective analysis compared
      the two techniques in terms of infection rates. METHODS: 152 patients (aged 17-85
      years, mean=55.4 years) were included in the final analysis; 95 received bolt-kit
      silver-bearing catheters and 57 received conventionally implanted silver-bearing
      catheters. The primary endpoint combined infection parameters: occurrence of
      positive CSF culture, colonization of catheter tips, or elevated CSF white blood
      cell counts (>4/MUl). Secondary outcome parameters were presence of
      microorganisms in CSF or on catheter tips. Incidence of increased CSF cell counts
      and number of patients with catheter malposition were also compared. RESULTS: The
      primary outcome, defined as analysis of combined infection parameters (occurrence
      of either positive CSF culture, colonization of the catheter tips or raised CSF
      white blood cell counts >4/MUl)was not significantly different between the groups
      (58.9% bolt-kit group vs. 63.2% conventionally implanted group, p=0.61, chi
      square-test). The bolt-kit group was non-inferior and not superior to the
      conventional group (relative risk reduction of 6.7%; 90% confidence interval: 
      19.9% to 25.6%). Secondary outcomes showed no statistically significant
      difference in the incidence of microorganisms in CSF (2.1% bolt-kit vs. 5.3%
      conventionally implanted; p=0.30; chi-square-test). CONCLUSIONS: This analysis
      indicates that silver-bearing EVD catheters implanted with a bolt-kit system
      outside the operating room do not significantly elevate the risk of CSF infection
      as compared to conventional implant methods.

PMID- 24908222
TI  - Progressive multifocal leukoencephalopathy presenting as a single ring-enhancing
      lesion.

PMID- 24908205
TI  - Cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for
      noninfectious intermediate, posterior, and panuveitis.
AB  - OBJECTIVE: To evaluate the 3-year incremental cost-effectiveness of fluocinolone
      acetonide implant versus systemic therapy for the treatment of noninfectious
      intermediate, posterior, and panuveitis. DESIGN: Randomized, controlled, clinical
      trial. PARTICIPANTS: Patients with active or recently active intermediate,
      posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment
      Trial. METHODS: Data on cost and health utility during 3 years after
      randomization were evaluated at 6-month intervals. Analyses were stratified by
      disease laterality at randomization (31 unilateral vs 224 bilateral) because of
      the large upfront cost of the implant. MAIN OUTCOME MEASURES: The primary outcome
      was the incremental cost-effectiveness ratio (ICER) over 3 years: the ratio of
      the difference in cost (in United States dollars) to the difference in quality
      adjusted life-years (QALYs). Costs of medications, surgeries, hospitalizations,
      and regular procedures (e.g., laboratory monitoring for systemic therapy) were
      included. We computed QALYs as a weighted average of EQ-5D scores over 3 years of
      follow-up. RESULTS: The ICER at 3 years was $297,800/QALY for bilateral disease,
      driven by the high cost of implant therapy (difference implant - systemic
      [Delta]: $16,900; P < 0.001) and the modest gains in QALYs (Delta = 0.057; P =
      0.22). The probability of the ICER being cost-effective at thresholds of
      $50,000/QALY and $100,000/QALY was 0.003 and 0.04, respectively. The ICER for
      unilateral disease was more favorable, namely, $41,200/QALY at 3 years, because
      of a smaller difference in cost between the 2 therapies (Delta = $5300; P = 0.44)
      and a larger benefit in QALYs with the implant (Delta = 0.130; P = 0.12). The
      probability of the ICER being cost-effective at thresholds of $50,000/QALY and
      $100,000/QALY was 0.53 and 0.74, respectively. CONCLUSIONS: Fluocinolone
      acetonide implant therapy was reasonably cost-effective compared with systemic
      therapy for individuals with unilateral intermediate, posterior, or panuveitis
      but not for those with bilateral disease. These results do not apply to the use
      of implant therapy when systemic therapy has failed or is contraindicated. Should
      the duration of implant effect prove to be substantially >3 years or should large
      changes in therapy pricing occur, the cost-effectiveness of implant versus
      systemic therapy would need to be reevaluated.

PMID- 24908223
TI  - Perioperative complication and surgical outcome in patients with spine
      metastases: retrospective 200-case series in a single institute.
AB  - OBJECTIVE: Metastatic spinal disease requires a multidisciplinary approach with
      advanced surgical techniques which improve longevity and the quality of life. The
      purpose of this study is to compare the surgical outcomes and perioperative
      complications and mortality among en bloc, debulking, and palliative surgeries in
      patients with spinal metastasis. METHODS: From 2005 to 2010, 200 patients who
      underwent surgical treatment for spinal metastases were enrolled retrospectively.
      Clinical analysis included primary cancer type, survival following the diagnosis
      of cancer, postoperative survival, Tokuhashi score, postoperative functional
      status, postoperative complications and mortality depending on the surgery type.
      Enrolled patients were divided into 3 groups: en bloc excision, debulking
      curettage, and palliative surgery. Surgical outcomes including perioperative
      complication and mortality were compared based on the surgery type. RESULTS: The
      mean age was 59.9 years (range 21-87). The major types of primary cancer were
      lung (42 cases), liver (27 cases), and colorectal cancer (27 cases). 62 surgeries
      (31.0%) were en bloc excisions, 82 (41.0%) were debulking, and 56 (28.0%) were
      palliative operations. The mean Tokuhashi score was 9.2+/-3.3 in the en bloc
      group, 7.2+/-3.0 in the debulking group and 8.2+/-2.6 in the palliative group
      (p=0.001, ANOVA). Mean postoperative survivals were 17.9+/-22.1 months in the en
      bloc group, 7.0+/-11.7 months in the debulking group and 8.5+/-10.8 months in the
      palliative group (p=0.022, ANOVA). There were 8 (12.9%) postoperative
      complications in the en bloc group, 17 (20.7%) in the debulking group, and 8
      (14.3%) in the palliative group (p=0.016, chi-square). Three patients (4.8%) in
      the en bloc group had multiple complications, as did 5 (6.1%) in the debulking
      group and 2 (3.6%) in the palliative group (p=0.925, chi-square). Among 21 total
      perioperative deaths, 6 (28.6%) were in the en bloc group, 10 (47.6%) in the
      debulking group, and 5 (23.8%) in the palliative group (p=0.618, chi-square).
      CONCLUSION: Postoperative complications were most common in the debulking group
      compared to the en bloc and palliative groups, despite the fact that there were
      no differences in the improvement of neurologic deficits after surgery.
      Therefore, selecting the proper surgery based on the patients' symptoms and
      neurologic status is of great significance in the planning stage of the surgery.

PMID- 24908224
TI  - Can DTI fiber tracking of the optic radiations predict visual deficit after
      surgery?
AB  - OBJECT: Sparing optic radiations can be of paramount importance during epilepsy
      surgery of the temporal lobe. The anatomical heterogeneity of the Meyer's loop of
      the optic radiations could be assessed by means of diffusion tensor tractography.
      We used temporal lobe surgery as a lesion model to validate this method. MATERIAL
      AND METHODS: We analyzed the distance between the temporal pole (TP) and Meyer's
      loop (ML) and the correlation between visual impairment and the percentage of
      virtual fibers injured. MRI studies were performed in 18 patients and 13
      controls. Diffusion tensor imaging (DTI) with fiber tracking was performed using
      four different algorithms and various gradient directions (15 or 32) and
      fractional anisotropy (FA) thresholds (0.18, 0.20, and 0.22). To find the best
      DTI model, we tested each gradient direction and FA threshold on 16 operated
      patients by pre- and post-operative visual field testing that analyzed the
      percentage of virtual fibers damaged on 3-month-post-operative MRIs. RESULTS:
      Marked individual differences were noted in the TP-ML distances (mean: 25.4mm;
      range 18.2-38.3mm; standard deviation: 4.7) but with no significant difference
      between patients and controls (p=0.9). The percentage of virtual fibers
      reconstructed by tracking and damaged by surgery was correlated with visual
      impairment. Significant differences appeared between algorithm types. The tensor
      line algorithm with 15-direction resolution and an anisotropy threshold of 0.18
      seemed to be the most relevant. A threshold of 5.5% of injured virtual fiber
      could predict a visual defect with a sensitivity of 71.4% and a specificity of
      87.5%. CONCLUSION: Optic radiation tractography by DTI could be a useful method
      to assess an individual patient's risk of postoperative visual deficit.

PMID- 24908225
TI  - Ventriculocisternostomy versus ventriculoperitoneal shunt in the treatment of
      hydrocephalus: a retrospective, long-term observational study.
AB  - OBJECTIVE: The goal of this study was the retrospective analysis of long-term
      data on endoscopic ventriculocisternostomy versus ventriculoperitoneal shunt
      placement in the treatment of hydrocephalus. METHODS: A total of 159 patients
      were included in the study. One hundred and twenty-three patients received a
      ventriculoperitoneal shunt, whereas 36 patients were treated with an endoscopic
      procedure. Only patients with a postoperative observation period of at least 3
      years were included in the analyses of the long-term data. In addition to general
      patient and operation data, the number and frequency of perioperative
      complications (infections, dysfunctions) and the frequency and type of necessary
      revision operations were collected. RESULTS: The average observation period was
      69 months for both groups. The risk of operative revision was significantly
      elevated in the shunt group despite a comparable observation period. Whereas
      86.11% of the endoscopy group did not require an operative revision, that only
      applied to 68.85% of the shunt group. The complication rate was 42.7% in the
      shunt group per procedure, which was clearly higher than in the endoscopy group
      at only 9.4%. CONCLUSION: The risk of operative revision and/or complications is
      significantly lower in the endoscopic ventriculocisternostomy group compared to
      the ventriculoperitoneal shunt group. Given the appropriate indication,
      endoscopic ventriculocisternostomy is thus the treatment of choice.

PMID- 24908226
TI  - Recovery of peripheral muscle function from fatiguing exercise and daily physical
      activity level in patients with multiple sclerosis: a case-control study.
AB  - OBJECTIVES: Delayed recovery of muscle function following exercise has been
      demonstrated in the lower limbs of patients with multiple sclerosis (MS).
      However, studies examining this in the upper limbs are currently lacking. This
      study compared physical activity level (PAL) and recovery of upper limb muscle
      function following exercise between MS patients and healthy inactive controls.
      Furthermore, the relationship between PAL and muscle recovery was examined.
      METHODS: PAL of 19 MS patients and 32 controls was measured using an
      accelerometer for 7 consecutive days. Afterwards, recovery of muscle function was
      assessed by performing a fatiguing upper limb exercise test with subsequent
      recovery measures. RESULTS: Muscle recovery of the upper limb muscles was similar
      in both groups. Average activity counts were significantly lower in MS patients
      than in the control group. MS patients spent significantly more time being
      sedentary and less time on activities of moderate intensity compared with the
      control group. No significant correlation between PAL and recovery of muscle
      function was found in MS patients. CONCLUSIONS: Recovery of upper limb muscle
      function following exercise is normal in MS patients. MS patients are less
      physically active than healthy inactive controls. PAL and recovery of upper limb
      muscle function appear unrelated in MS patients.

PMID- 24908227
TI  - Diagnosis and management of functional neurological symptoms: The Dutch
      experience.
AB  - OBJECTIVES: Functional neurological symptoms (FNS) were considered as a
      psychiatric disorder at the beginning of the 20th century (conversion disorder).
      Psychiatrists performed diagnosis and treatment throughout most of the past
      century in the Netherlands, but in the latest decades patients were usually
      firstly referred to neurologists. The aim of this study was to investigate the
      opinions of today's neurologists, psychiatrists and rehabilitation physicians in
      the Netherlands, regarding pathogenesis, diagnosis and treatment of FNS. DESIGN:
      An electronic questionnaire was sent to all neurologists registered with the
      Dutch Society for Neurology and to the members of the Department for Consultation
      liaison and General Hospital Psychiatry. RESULTS: 343 of 780 neurologists, 64 of
      197 psychiatrists and 47 of 750 rehabilitation physicians completed the
      questionnaire. 60% of neurologists and 67% of psychiatrists considered disordered
      brain functioning together with psychogenic factors responsible for FNS. 29% of
      neurologists and 88% of psychiatrists felt a psychiatrist was needed for
      diagnosis. 55% of neurologists and 88% of psychiatrists preferred combined
      treatment consisting of explaining FNS to patients, psychotherapy and
      physiotherapy provided by a therapist trained in FNS. 15% of neurologists
      preferred only physiotherapy. CONCLUSION: Most neurologists and psychiatrists did
      not consider FNS as a mere psychiatric disorder, but counted disordered brain
      functioning together with psychogenic factors responsible for FNS. Subsequently,
      according to the majority of neurologists and psychiatrists FNS should not be
      solely diagnosed and treated by psychiatrists. These results can help to
      formulate treatment strategies.

PMID- 24908228
TI  - Diffuse leukoencephalopathy with spheroids: biopsy findings and a novel mutation.

PMID- 24908229
TI  - Development of normal pressure hydrocephalus after the placement of a pipeline
      embolization device for the treatment of a large aneurysm: case report.

PMID- 24908230
TI  - Characterization of pituitary tumor transforming gene in meningiomas.
AB  - BACKGROUND: Pituitary tumor transforming gene (PTTG) is an oncogene and has been
      detected in several tumors of unrelated histological origin. However, its role in
      meningiomas is unknown so far. We aim to investigate PTTG expression in
      intracranial meningiomas, and clarify the relationship between PTTG and the
      histopathological types of tumors. MATERIALS AND METHODS: Over a 7-year period,
      195 meningioma specimens were collected from 195 patients. Seventeen
      nonneoplastic meningeal tissues were used as controls. We analyze PTTG expression
      by tissue microarray with immunohistochemistry. RESULTS: Immunoexpression of PTTG
      was identified in 172 of 195 meningiomas, accounting for 88.2%. All of
      immunoexpression of tumors were found to be cytoplasmic, and no nuclear
      expression was observed. In the control group, there were 3 of 17 specimens
      (17.6%) with positive PTTG expression. The percentage of high expression WHO
      subtypes of meningiomas ranged from 0% to 95.7%. We further stratified the tumors
      into 3 subgroups based on pathological grading (WHO grade I, WHO grade II and
      III, control), and there was significant intergroup difference in PTTG expression
      (p<0.001). CONCLUSION: This study demonstrated that PTTG was expressed in most of
      meningioma tissues, and the degree of PTTG immunostaining was variable in the
      subtypes of tumors. Further investigations into PTTG expression are required to
      broaden the pathogenesis research of meningiomas.

PMID- 24908231
TI  - HIF signaling pathway in pheochromocytoma and other neuroendocrine tumors.
AB  - Hypoxia-inducible factors (HIFs) are transcription factors controlling energy,
      iron metabolism, erythropoiesis, and development. Dysregulation of these proteins
      contributes to tumorigenesis and cancer progression. Recent findings revealed the
      important role of HIFs in the pathogenesis of neuroendocrine tumors, especially
      pheochromocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamine
      producing tumors arising from sympathetic- or parasympathetic-derived chromaffin
      tissue. To date, eighteen PHEO/PGL susceptibility genes have been identified.
      Based on the main signaling pathways, PHEOs/PGLs have been divided into two
      clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor
      signaling and protein translation pathways. Recent data suggest that both
      clusters are interconnected via the HIF signaling and its role in tumorigenesis
      is supported by newly described somatic and germline mutations in HIF2A gene in
      patients with PHEOs/PGLs associated with polycythemia, and in some of them also
      with somatostatinoma. Moreover, HIFalpha signaling has also been shown to be
      upregulated in neuroendocrine tumors other than PHEO/PGL. Some of these tumors
      are components of hereditary tumor syndromes which can be associated with
      PHEO/PGL, but also in ileal carcinoids or melanoma. HIF signaling appears to be
      one of the crucial players in tumorigenesis, which could suggest new therapeutic
      approaches for treatment of neuroendocrine tumors. 

PMID- 24908232
TI  - Thyroid nodules: pathophysiological insight on oncogenesis and novel diagnostic
      techniques.
AB  - Thyroid nodules are a very frequent pathology among common population. Despite
      the vast majority of them are of benign origin, the incidence of thyroid cancer
      is currently rather rising. Although there are several risk factors of thyroid
      cancer and several clinical, ultrasound, biochemical and molecular diagnostic
      markers, the exact mechanisms of thyroid oncogenesis and the linkage between
      thyroid nodule ultrasound appearance and its biological character remain unclear.
      While ionizing radiation is the only one well-known risk factor for thyroid
      cancer, the significance of some others remains unclear. The aim of our review
      was to discuss some not completely known pathophysiological mechanisms involved
      in thyroid oncogenesis as hypothyroidism, mutations of genes regulating cell
      proliferation, thyroid autoimmunity and pregnancy and to describe
      pathophysiological background of some ultrasound markers of thyroid cancer (size,
      echogenicity, vascularization, calcifications and stiffness). Better knowledge in
      this field is crucial for development of novel diagnostic techniques and
      therapeutic approaches. For example, the analysis of BRAF, RAS and other
      mutations in cytological samples may help to distinction between follicular
      thyroid carcinoma and follicular thyroid adenoma and may significantly decrease
      the number of unnecessary surgery among patients with thyroid nodules.
      Alternatively, the different malign cells growth, angiogenesis, destructions of
      thyroid follicles, reparative changes, growth retardation, fibrosis and increased
      interstitial fluid pressure implicate the typical ultrasound appearance of
      papillary thyroid cancer (hypoechogenicity, irregular vascularization,
      microcalcifications, stiffness) which is essential to catch the suspicious
      nodules on the basis of their ultrasound appearance among large amount of benign
      nodules. 

PMID- 24908233
TI  - Steroid hormones in the development of postpartum depression.
AB  - Postpartum depression affects 10-15 % women after childbirth. There is no
      currently generally accepted theory about the causes and mechanisms of postpartum
      mental disorders. The principal hypothesis concerns the association with sudden
      changes in the production of hormones affecting the nervous system of the mother
      and, on the other hand, with the ability of receptor systems to adapt to these
      changes. We observed changes in steroidogenesis in the period around spontaneous
      delivery. We collected three samples of maternal blood. The first sampling was 4
      weeks prior to term; the second sampling was after the onset of uterine
      contractions (the beginning of spontaneous labour); the third sampling was during
      the third stage of labour (immediately after childbirth). Additionally, we
      collected mixed umbilical cord blood. The almost complete steroid metabolome was
      analyzed by gas chromatography-mass spectrometry followed by RIA for some
      steroids. Mental changes in women in the peripartum period were observed using
      the Hamilton Depression Rating Scale. The local Ethics Committee approved the
      study. We found already the changes in androgens levels correlating with
      postpartum mood disorders four weeks prior to childbirth. The strongest
      correlations between steroid and postpartum mood change were found in venous
      blood samples collected from mothers after childbirth and from umbilical cord
      blood. The main role played testosterone, possibly of maternal origin, and
      estrogens originating from the fetal compartment. These results suggest that
      changes in both maternal and fetal steroidogenesis are involved in the
      development of mental changes in the postpartum period. Descriptions of changes
      in steroidogenesis in relation to postpartum depression could help clarify the
      causes of this disease, and changes in some steroid hormones are a promising
      marker of mental changes in the postpartum period. 

PMID- 24908234
TI  - Fructosamine 3-kinase and glyoxalase I polymorphisms and their association with
      soluble RAGE and adhesion molecules in diabetes.
AB  - Advanced glycation end-products (AGEs) are key players in pathogenesis of long
      term vascular diabetes complications. Several enzymes such as fructosamine 3
      kinase (FN3K) and glyoxalase I (GLO I) are crucial in preventing glycation
      processes. The aim of our study was to evaluate an association of FN3K
      (rs1056534, rs3848403) and GLO1 rs4746 polymorphisms with parameters of
      endothelial dysfunction and soluble receptor for AGEs (sRAGE) in 595 diabetic and
      non-diabetic subjects. Genotypic and allelic frequencies of mentioned
      polymorphisms did not differ between subgroups. In diabetic patients significant
      differences were observed in sRAGE concentrations according to their rs1056534
      and rs3848403 genotype. While GG and CG genotypes of rs1056534 with mutated G
      allele were associated with significant decrease of sRAGE (GG: 1055+/-458 and CG:
      983+/-363 vs. CC: 1796+/-987 ng/l, p<0.0001), in rs3848403 polymorphism TT
      genotype with mutated T allele was related with significant sRAGE increase (TT:
      1365+/-852 vs. CT: 1016+/-401 and CC: 1087+/-508 ng/l, p=0.05). Significant
      differences in adhesion molecules were observed in genotype subgroups of GLO1
      rs4746 polymorphism. In conclusion, this is the first study describing
      significant relationship of FN3K (rs1056534) and (rs3848403) polymorphisms with
      concentration of sRAGE in patients with diabetes. 

PMID- 24908235
TI  - Rosiglitazone influences the expression of leukocyte adhesion molecules and CD14
      receptor in type 2 diabetes mellitus patients.
AB  - Diabetes mellitus is associated with increased inflammatory response, which may
      contribute to atherosclerosis progression. Experimental results demonstrated anti
      inflammatory activity of glitazones; their effect on leukocyte adhesion molecules
      has not been studied to date. We therefore studied the effect of rosiglitazone
      treatment on leukocyte surface expression of adhesion molecules in patients with
      type 2 diabetes mellitus and compared our results with findings in healthy
      subjects. 33 subjects with type 2 diabetes and 32 healthy controls were included;
      patients were examined at baseline and after 5 months of rosiglitazone treatment
      (4 mg/d). Leukocyte expression of adhesion molecules LFA-1, CD18 and ICAM-1 was
      quantified using flow cytometry; in addition, CD14 (lipopolysaccharide receptor)
      expression was analyzed as a marker of nonspecific immunity. The expression of
      examined molecules at baseline was higher in patients compared to controls.
      Despite only mild decrease in blood glucose, rosiglitazone treatment induced
      substantial decrease of CD18 and CD14 expression and borderline decrease of LFA-1
      and ICAM-1 expression (on monocytes only). We thus observed improvement in the
      expression of leukocyte inflammatory markers after rosiglitazone treatment. This
      effect is supposed to be mediated by direct effect of rosiglitazone on PPAR-gamma
      receptors on leukocytes. 

PMID- 24908236
TI  - Three months of regular aerobic exercise in patients with obesity improve
      systemic subclinical inflammation without major influence on blood pressure and
      endocrine production of subcutaneous fat.
AB  - The aim of our study was to explore the effects of regular aerobic exercise on
      anthropometric, biochemical and hormonal parameters and mRNA expression of
      selected factors involved in metabolic regulations in subcutaneous adipose tissue
      of patients with obesity. Fifteen obese women with arterial hypertension
      underwent a three-month exercise program consisting of 30 min of aerobic exercise
      3 times a week. Fifteen healthy lean women with no intervention served as a
      control group. Obese group underwent anthropometric measurements, blood sampling,
      subcutaneous adipose tissue (SCAT) biopsy and 24-h blood pressure monitoring at
      baseline and after three months of exercise, while control group was examined
      only once. At baseline, obese group had increased SCAT expression of
      proinflammatory cytokines and adipokines relative to control group. Three months
      of regular exercise improved anthropometric parameters, decreased CRP, blood
      glucose and HOMA-IR, while having no significant effect on lipid profile and
      blood pressure. Gene expressions in SCAT were not affected by physical activity
      with the exception of increased aquaporin-3 mRNA expression. We conclude that
      three months of regular exercise decrease systemic subclinical inflammation with
      only minor influence on the blood pressure and the endocrine function of
      subcutaneous fat. 

PMID- 24908237
TI  - Does impedance measure a functional state of the body fat?
AB  - The aim was to compare methods of body fat measurement in different BMI groups.
      An additional aim was to discuss differences reflecting the structural and
      functional changes of fat tissue. The study group included 130 adult Caucasian
      women stratified by body mass index (BMI): 18-24.99 (n=30), 25-29.99 (n=26), 30
      34.99 (n=33), 35-39.99 (n=30), and BMI>/=40 (n=11). Bioelectrical impedance was
      performed using Tanita TBF 410 GS, Bodystat 1500, and Omron BF 300. A caliper
      type Best was also applied. Correspondence of four methods with DEXA was assessed
      using the Bland-Altman and ANOVA analyses. Measurements by BIA were not
      significantly different from DEXA up to BMI of 30, but DEXA significantly
      overestimated in the higher BMI subgroup by all three methods. Caliper
      measurement significantly underestimated DEXA in all BMI subgroups. BIA methods
      overestimated DEXA for the obese subjects. Tanita did statistically the best. The
      Caliper test appeared less preferable than the BIA methods, especially in the
      higher BMI subgroup. DEXA and Caliper measurements seem to be the best estimate
      of structural (anatomical) fat quantity. We hypothesize that BIA methods could
      also measure some other physiopathological conditions like inflammation,
      hydration or cell infiltration of fat. 

PMID- 24908238
TI  - Post-exercise changes of beta hydroxybutyrate as a predictor of weight changes.
AB  - The aim was to find the differences in ketogenesis initiation in the early period
      after the exercise in obese patients and to find if these changes may predict the
      weight loss during the physical activity program. 96 females were enrolled. A
      clamped heart rate test (CHR) was performed to establish comparable exercise
      intensity. Blood samples for beta hydroxybutyrate (BOHB) assessment were
      collected prior, immediately after and 60 min after the test. Patients underwent
      a three month fitness program. Anthropometric measurements (fat mass and
      biochemical parameters) were measured. An energy intake was monitored and
      comparable in all subjects. A significant increase of BOHB was found in 60(th)
      minute after the test, when compared with initiation levels (BOHB1 vs. BOHB3;
      p=0.03). This increase correlates with % fat mass (R=0.196; p=0.02) and
      negatively with age (R= -0.147; p=0.05) and with weight reduction during the
      three-month program (R= -0.299; p=0.03). Serum BOHB increase after the single
      exercise may detect individuals with an ability to induce lipolysis in three
      month program of physical activity for obese patients. 

PMID- 24908239
TI  - Stent thrombosis is not increased following percutaneous coronary intervention in
      patients with non-insulin dependent diabetes mellitus taking metformin.
AB  - OBJECTIVE: Recent studies have suggested that metformin may inhibit
      endothelialization following limus-eluting stent (LES) placement and may increase
      the risk of stent thrombosis. Therefore, we assessed the impact of metformin on
      stent thrombosis and major adverse cardiovascular events (MACE) in non-insulin
      dependent diabetes mellitus (NIDDM) patients who receive drug-eluting stents
      (DES). METHODS: We assessed the impact of metformin and stent type on stent
      thrombosis, MACE, and death in NIDDM patients following DES placement. Of the
      1201 patients included, 74.8% received LES, 25.2% received paclitaxel-eluting
      stents (PES), and 55% were taking metformin. RESULTS: There was no difference in
      stent thrombosis, regardless of stent type or metformin use. While Kaplan-Meier
      curves demonstrated reduced MACE (p = 0.007) and death (p = 0.006) with metformin
      use, multivariate analysis demonstrated that stent type and metformin use were
      not associated with outcome. CONCLUSION: In NIDDM patients, metformin use or
      stent type following DES placement did not increase stent thrombosis and MACE
      rates.

PMID- 24908240
TI  - Markers of atherosclerotic development in children with familial
      hypercholesterolemia: a literature review.
AB  - OBJECTIVE: Atherosclerosis is a multi-step process, where lipids, inflammatory
      and hemostatic mediators orchestrate plaque formation and progression, which
      subsequently may lead to myocardial infarction and ischemic stroke. Familial
      hypercholesterolemia (FH) is associated with increased risk of premature
      atherosclerosis due to the genetically determined elevated low density
      lipoprotein (LDL)-cholesterol seen in these individuals. Children with FH are
      suitable to investigate the isolated effect of elevated LDL-cholesterol on early
      markers of atherosclerosis. The aim of the present paper was to review the
      literature to summarize the findings of atherosclerotic markers in children with
      FH to better understand how elevated LDL-cholesterol per se promotes
      atherogenesis. METHODS: We conducted a systematic literature search from the
      years 1990-2013, resulting in identification of 903 articles. In order to
      investigate whether intima-media thickness (IMT) is different in children with
      and without FH, we conducted a meta-analysis of the studies comparing FH children
      with a control group. RESULTS: 37 original articles were included. Among these,
      24 reported subclinical measurements, whereas other articles reported
      measurements of atherogenic lipids (n = 9), inflammatory markers (n = 10),
      hemostatic markers (n = 6) and other surrogate markers of atherosclerosis (n =
      7). In the meta-analysis (n = 8), IMT was significantly thicker in children with
      FH than in control children (weighted mean difference 0.06, 95% confidence
      interval [0.01, 0.11]). CONCLUSION: Elevated LDL-cholesterol distinguishes
      children with and without FH, but these groups of children also differ in several
      other ways. In particular, children with FH display a variety of changes
      reflecting both the lipid and the inflammatory arm of atherosclerosis. The IMT
      meta-analysis result strengthens the evidence of early atherosclerotic
      development in children with FH. In a clinical perspective, early diagnosing and
      treatment of children with FH is of high importance to attenuate development of
      the potential ongoing early atherosclerotic process in these individuals.

PMID- 24908241
TI  - Acupuncture for acute stroke: study protocol for a multicenter, randomized,
      controlled trial.
AB  - BACKGROUND: Acupuncture has been widely used as a treatment for stroke in China
      for more than 3,000 years. However, previous research has not yet shown that
      acupuncture is effective as a stroke treatment. We report a protocol for a
      multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate
      the efficacy and safety of acupuncture on acute ischemic stroke. METHODS/DESIGN:
      In a prospective trial involving three hospitals in the Zhejiang Province (China)
      250 patients with a recent (less than 1 week previous) episode of ischemic stroke
      will be included. Patients will be randomized into two groups: an acupuncture
      group given scalp acupuncture and electroacupuncture, and a control group given
      no acupuncture. Eighteen treatment sessions will be performed over a three-week
      period. The primary outcome will be measured by changes in the National
      Institutes of Health Stroke Scale score at the one, three, and four-week follow
      up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for
      motor function; 2) the mini-mental state examination and Montreal cognitive
      assessment for cognitive function; 3) the video-fluoroscopic swallowing study for
      swallowing ability; and 4) the incidence of adverse events. DISCUSSION: This
      trial is expected to clarify whether or not acupuncture is effective for acute
      stroke. It will also show if acupuncture can improve motor, cognitive, or
      swallowing function. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR
      TRC-12001971.

PMID- 24908242
TI  - Ileal effect on blood glucose, HbA1c, and GLP-1 in Goto-Kakizaki rats.
AB  - BACKGROUND: There have been enumerable studies on the effects of glucagon-like
      peptide-1 (GLP-1) on satiety and pancreatic islet function, stimulating the
      advocacy of surgical transposition of the ileum (rich in GLP-1-generating L
      cells) higher in the gastrointestinal tract for earlier stimulation. In the Goto
      Kakizaki rat with naturally occurring type 2 diabetes, we studied the influence
      of ileal exclusion (IE) and ileal resection (IR) on blood glucose, hemoglobin A1c
      (HbA1c), and GLP-1. METHODS: In six control (Ctrl), 10 IE, and 10 IR rats, over
      12 weeks of follow-up, we determined blood glucose, HbA1c, and GLP-1. RESULTS:
      Two animals in the IE and IR groups did not survive to week 13. Both operated
      groups weighed more than the Ctrl group at baseline and at 13 weeks; thus, IE and
      IR did not retard weight gain (p < 0.05). All three groups were equally
      hyperglycemic at week 13: 255 +/- 10.2 Ctrl, 262 +/- 11.0 IE, 292 +/- 17.8 IR
      (mg/dl +/- SEM). The three groups had statistically identical markedly elevated
      HbA1c percentages at week 13: 14.7 +/- 28 Ctrl, 11.7 +/- 3.4 IE, 13.8 +/- 3.5 IR
      (% +/- SEM). The end-study GLP-1 values (pM +/- SEM) were 5 +/- 0.9 Ctrl, 33 +/-
      8.9 IE, and 25 +/- 6.7 IR. P values for intergroup differences were IE vs. Ctrl
      0.02, IR vs. Ctrl 0.02, and IE vs. IR 0.59. CONCLUSIONS: Neither IE nor IR
      resulted in a decrease in the mean GLP-1 level. On the contrary, the exclusion or
      resection of the L-cell rich ileum raised GLP-1 levels 5- to 6-fold. This
      increase in the GLP-1 was not associated with the mitigation of hyperglycemia or
      elevated HbA1c levels.

PMID- 24908243
TI  - Outcome analysis of single incision vs traditional multiport sleeve gastrectomy:
      a matched cohort study.
AB  - BACKGROUND: Single incision laparoscopy remains controversial due to technical
      challenges which may cause suboptimal outcomes. This study aims to evaluate the
      feasibility and equivalency of the single incision sleeve gastrectomy (SISG) when
      compared to the traditional multiport sleeve gastrectomy (MPSG) approach in a
      matched cohort evaluating technical aspects and postoperative results. METHODS:
      This is a retrospective analysis of prospectively collected data in a consecutive
      cohort of 113 SG (MPSG = 77, SISG = 36). The 36 patients who underwent SISG were
      included as the case group. Thirty-six MPSG patients were included in the control
      group, in 1:1 ratio with cases after matching for BMI, age, race, gender, and
      additional demographic data. Operative time (OT) in minutes and length of stay
      (LOS) in days was measured and excess weight loss (EWL) at 6 months and 1 year
      was collected and evaluated. RESULTS: Mean BMI was equivalent (SISG 43.06, MPSG
      43.72, p = 0.36). Mean OT for the SISG was 116.78 and 118.25 for the MPSG (p =
      0.84), and mean LOS was 1.80 for the SISG and 1.75 for the MSPG (p = 0.75). EWL
      at 6 months was 58.4 % for the SISG and 58.5 % for the MPSG (p = 0.98) and 72.3
      and 74.1 % (p = 0.77) for 1 year, respectively. There were no leaks in either
      group. There was one reoperation for postoperative bleeding in the MPSG group.
      CONCLUSIONS: Sleeve gastrectomy can be performed safely using single incision
      techniques with equivalent outcomes for weight loss.

PMID- 24908244
TI  - Iodine deficiency is higher in morbid obesity in comparison with late after
      bariatric surgery and non-obese women.
AB  - BACKGROUND: Iodine deficiency and obesity are worldwide-occurring health
      problems. Our purpose was to investigate the relationship between morbid obesity
      and iodine status, including subjects who lost weight after bariatric surgery.
      METHODS: Ninety morbidly obese women, 90 women with at least 18 months follow-up
      after bariatric surgery, and 45 healthy non-obese women were recruited. Urinary
      iodine concentration (UIC) was measured in a spot urinary sample and expressed as
      the iodine-to-creatinine ratio. RESULTS: Obese women showed a significantly lower
      UIC in comparison with non-obese women (96.6 (25.8-267.3) vs. 173.3 (47.0-493.6)
      MUg/g; p < 0.001), with a lesser proportion of subjects with adequate iodine
      status (46.6 vs. 83.3 %, p < 0.001). The mean UIC significantly increased among
      women who underwent bariatric surgery before the collection of the urinary sample
      (96.6 (25.8-267.3) vs. 131.9 (62.9-496.4) MUg/g; p < 0.001). No difference in UIC
      was detected between laparoscopic Roux-en-Y gastric bypass and laparoscopic
      sleeve gastrectomy. Univariate analysis showed that UIC negatively correlated
      with body mass index (BMI) (r = -0.278, p < 0.001) and positively with age (r =
      0.206, p = 0.002). Finally, multiple linear regression analyses showed that BMI
      was independently associated with UIC (beta = -0.312, p < 0.001; R (2) = 0.166).
      CONCLUSION: Obesity is an independent risk factor to iodine deficiency, almost in
      women. Whether more obese population needs to be considered as a vulnerable group
      and whether bariatric surgery can reverse iodine deficiency still remain to be
      elucidated.

PMID- 24908245
TI  - New-onset substance use disorder after gastric bypass surgery: rates and
      associated characteristics.
AB  - BACKGROUND: Substance use disorder (SUD) may develop de novo for a subgroup of
      weight loss surgery patients, particularly those who have had the Roux-en-Y
      gastric bypass (RYGB) procedure. The present study examined the rate of SUD in a
      broad sample of RYGB patients and identified associated behavioral and
      psychological factors. METHODS: Participants included 143 RYGB patients; the
      majority were women (n = 120; 83.9 %) and white (n = 135; 94.4 %). Participants
      completed a web-based survey assessing retrospective accounts of presurgical
      substance use, eating pathology, family history, and traumatic history,
      postsurgical substance use, life stressors, and global trait-like measures
      (emotion dysregulation, impulsivity, sensation-seeking, and coping skills).
      RESULTS: A subgroup (n = 28, 19.6 %) of post-RYGB patients met criteria for
      probable SUD; however, the majority of those who met SUD criteria postsurgery (n
      = 19, 68 %) did not report a pre-RYGB SUD history. Family history of substance
      abuse, poor coping skills, and potential life stressors were related to post-RYGB
      SUD, particularly for the new-onset group. Additionally, the majority of those
      who met criteria for pre-RYGB SUD (n = 21, 70 %) did not continue to meet SUD
      criteria following RYGB. CONCLUSIONS: Findings highlight a subgroup of post-RYGB
      patients reporting new-onset SUD, which is unexpected among middle-aged women.
      Importantly, findings also indicate that many patients with presurgical SUD did
      not relapse postsurgery. Assessing for family history of SUD and coping skills at
      the presurgical evaluation is recommended. Future research should identify
      psychological and physiological risk factors for SUD postsurgery and examine
      protective factors of those who discontinue substance use postsurgery.

PMID- 24908246
TI  - Cardiovascular risk profile in Mediterranean patients submitted to bariatric
      surgery and intensive lifestyle intervention: impact of both interventions after
      1 year of follow-up.
AB  - BACKGROUND: The aim was to compare obesity-related cardiovascular (CV) risk
      factors (classic and emerging) and the estimated CV risk at 10 years (calculated
      by REGICOR) in obese Mediterranean patients submitted to bariatric surgery and
      intensive lifestyle intervention at baseline and after 1 year of follow-up.
      METHODS: Patients submitted to bariatric surgery (n = 108) and standardized
      program of therapeutic changes in lifestyle (n = 90) were retrospectively
      included. Clinical history, physical examination, and laboratory analysis were
      routinely determined before weight loss intervention and at 1 year follow-up.
      RESULTS: Seventy-five percent of the surgery patients had a CV risk lower than 5
      % and not one patient had a 10-year CV risk higher than 15 %. The percentage of
      patients with comorbidities (diabetes and sleep apnea syndrome) was higher in the
      surgery group. Seventeen of the surgery patients had no comorbidities. The
      improvement in CV risk profile was significant higher in the surgery group. CV
      risk benefit of both intervention groups was related to baseline higher CV risk,
      with type 2 diabetes with poor metabolic control and high cholesterol levels
      being the most important predictors for surgery patients. Neither body mass index
      nor excess of weight loss was related to CV risk improvement. CONCLUSIONS:
      Mediterranean patients undergoing a weight loss intervention have a low CV risk.
      In comparison with lifestyle intervention, surgery induces a better improvement
      of CV risk. This benefit is related to estimated CV risk, presence of diabetes,
      and cholesterol levels at baseline. These observations should be taken into
      account in order to optimize health resources.

PMID- 24908247
TI  - Endothelial function in hypertensive obese patients: 1 year after surgically
      induced weight loss.
AB  - The aim of this study was to describe the effect of surgically induced weight
      loss on vascular function measured by flow-mediated dilatation (FMD) in
      hypertensive obese patients. This prospective study included 33 patients (78 %
      females, mean age 53 (9) years) undergoing bariatric surgery (BS). Before and 12
      months postoperatively, the BMI, 24-h ambulatory BP, high-sensitivity C-reactive
      protein (hs-CRP), leptin, homeostasis model assessment (HOMA IR), and abdominal
      fat were measured. Endothelial function was assessed by FMD. After BS, the excess
      body weight loss was 71 %; the 24-h [systolic 18(11)//diastolic 7(7) mmHg] BP
      values, hs-CRP, leptin, HOMA, and abdominal fat significantly decreased, with no
      changes in endothelial function. Weight loss achieved by BS was associated with a
      significant improvement in BP and metabolic and inflammation parameters, but FMD
      did not improve. 

PMID- 24908249
TI  - A reference genome for common bean and genome-wide analysis of dual
      domestications.
AB  - Common bean (Phaseolus vulgaris L.) is the most important grain legume for human
      consumption and has a role in sustainable agriculture owing to its ability to fix
      atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically
      anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared
      the genome for the common bean against the soybean genome to find changes in
      soybean resulting from polyploidy. Using resequencing of 60 wild individuals and
      100 landraces from the genetically differentiated Mesoamerican and Andean gene
      pools, we confirmed 2 independent domestications from genetic pools that diverged
      before human colonization. Less than 10% of the 74 Mb of sequence putatively
      involved in domestication was shared by the two domestication events. We
      identified a set of genes linked with increased leaf and seed size and combined
      these results with quantitative trait locus data from Mesoamerican cultivars.
      Genes affected by domestication may be useful for genomics-enabled crop
      improvement. 

PMID- 24908248
TI  - Variants near TERT and TERC influencing telomere length are associated with high
      grade glioma risk.
AB  - Glioma, the most common central nervous system cancer in adults, has poor
      prognosis. Here we identify a new SNP associated with glioma risk, rs1920116
      (near TERC), that reached genome-wide significance (Pcombined = 8.3 * 10(-9)) in
      a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma
      and replication data (1,644 cases and 7,736 controls). This region has previously
      been associated with mean leukocyte telomere length (LTL). We therefore examined
      the relationship between LTL and both this new risk locus and other previously
      established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684
      individuals). Alleles associated with glioma risk near TERC and TERT were
      strongly associated with longer LTL (P = 5.5 * 10(-20) and 4.4 * 10(-19),
      respectively). In contrast, risk-associated alleles near RTEL1 were
      inconsistently associated with LTL, suggesting the presence of distinct causal
      alleles. No other risk loci for glioma were associated with LTL. The
      identification of risk alleles for glioma near TERC and TERT that also associate
      with telomere length implicates telomerase in gliomagenesis. 

PMID- 24908250
TI  - Quantitative genome-wide enhancer activity maps for five Drosophila species show
      functional enhancer conservation and turnover during cis-regulatory evolution.
AB  - Phenotypic differences between closely related species are thought to arise
      primarily from changes in gene expression due to mutations in cis-regulatory
      sequences (enhancers). However, it has remained unclear how frequently mutations
      alter enhancer activity or create functional enhancers de novo. Here we use STARR
      seq, a recently developed quantitative enhancer assay, to determine genome-wide
      enhancer activity profiles for five Drosophila species in the constant trans
      regulatory environment of Drosophila melanogaster S2 cells. We find that the
      functions of a large fraction of D. melanogaster enhancers are conserved for
      their orthologous sequences owing to selection and stabilizing turnover of
      transcription factor motifs. Moreover, hundreds of enhancers have been gained
      since the D. melanogaster-Drosophila yakuba split about 11 million years ago
      without apparent adaptive selection and can contribute to changes in gene
      expression in vivo. Our finding that enhancer activity is often deeply conserved
      and frequently gained provides functional insights into regulatory evolution. 

PMID- 24908251
TI  - Genome-wide association analyses provide genetic and biochemical insights into
      natural variation in rice metabolism.
AB  - Plant metabolites are important to world food security in terms of maintaining
      sustainable yield and providing food with enriched phytonutrients. Here we report
      comprehensive profiling of 840 metabolites and a further metabolic genome-wide
      association study based on ~6.4 million SNPs obtained from 529 diverse accessions
      of Oryza sativa. We identified hundreds of common variants influencing numerous
      secondary metabolites with large effects at high resolution. We observed
      substantial heterogeneity in the natural variation of metabolites and their
      underlying genetic architectures among different subspecies of rice. Data mining
      identified 36 candidate genes modulating levels of metabolites that are of
      potential physiological and nutritional importance. As a proof of concept, we
      functionally identified or annotated five candidate genes influencing metabolic
      traits. Our study provides insights into the genetic and biochemical bases of
      rice metabolome variation and can be used as a powerful complementary tool to
      classical phenotypic trait mapping for rice improvement. 

PMID- 24908252
TI  - Hybrid surgery for multilevel cervical degenerative disc diseases: a systematic
      review of biomechanical and clinical evidence.
AB  - PURPOSE: The optimal surgical technique for multilevel cervical degenerative disc
      diseases (DDD) remains controversial. Hybrid surgery (HS) incorporating anterior
      cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) is
      increasingly performed for cervical DDD. This study aims to evaluate the
      biomechanical and clinical evidence available for HS and to provide a systematic
      review of current understanding of HS. METHODS: This systematic review was
      undertaken by following the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses Statement. Multiple databases and online registers of clinical
      trials were searched up to February 2014. The biomechanical and clinical studies
      on HS for cervical DDD written in English were included. Two authors
      independently assessed methodological quality and extracted data. RESULTS:
      Fifteen studies including eight biomechanical studies and seven clinical studies
      were indentified. The biomechanical studies showed that HS was benefit to motion
      preservation of the operative levels and revealed less adverse effect on adjacent
      segments. All clinical studies demonstrated improvement in validated functional
      scores after HS. Segment motion and immobilization were achieved at the
      arthroplasty level and arthrodesis level, respectively. Postoperative assessments
      and complication rate were similar or in favor of HS when comparing with ACDF or
      CDR. However, the overall quality of evidence for HS was low to very low.
      CONCLUSIONS: There is a paucity of high quality evidence for HS. HS may be a safe
      and efficacious technique to benefit a select group of multilevel cervical DDD,
      which is needed to be confirmed by further prospective, randomized controlled
      trials.

PMID- 24908253
TI  - Down-regulated expression of vimentin induced by mechanical stress in fibroblasts
      derived from patients with ossification of the posterior longitudinal ligament.
AB  - PURPOSE: The aim of this study was to investigate the potential role of vimentin
      in the signal transduction pathways initiated by mechanical stimulation that
      contribute to ossification of the posterior longitudinal ligament of the spine
      (OPLL). METHODS: We investigated the effects of in vitro cyclic stretch on
      cultured spinal ligament cells derived from OPLL (OPLL cells) and non-OPLL (non
      OPLL cells) patients. The expression levels of the osteoblast-specific genes
      encoding osteocalcin (OCN), alkaline phosphatase (ALP), and type I collagen (COL
      I) were assessed by semi-quantitative reverse transcription-polymerase chain
      reaction. Vimentin protein expression in OPLL cells was detected by Western
      blotting. Small interfering RNA (siRNA) interference targeting vimentin was
      performed in OPLL cells induced by mechanical stress, and the expression levels
      of OCN, ALP and COL I were assessed. RESULTS: In response to mechanical stretch,
      the expression levels of OCN, ALP, and COL I were increased in OPLL cells,
      whereas no change was observed in non-OPLL cells. Furthermore, knockdown of
      vimentin protein expression by siRNA resulted in an increase in the mRNA
      expression levels of OCN, ALP, and COL I. CONCLUSION: The down-regulation of
      vimentin induced by mechanical stress plays an important role in the progression
      of OPLL through the induction of osteogenic differentiation in OPLL cells.

PMID- 24908254
TI  - C1-C2 pigmented villonodular synovitis and clear cell carcinoma: unexpected
      presentation of a rare disease and a review of the literature.
AB  - INTRODUCTION: Pigmented Villonodular synovitis (PVNS) is a rare vertebral
      pathology--around 50 reports, only 3 concerning C1-C2 location. CASE REPORT: A 64
      year-old man, submitted to a right nephrectomy for a clear cell carcinoma,
      presented with an asymptomatic osteolytic C1-C2 lesion. Even though the diagnosis
      of metastatic disease was the most probable, the presence of a solitary lesion
      without other osseous or systemic localization and the predicted low risk of
      recurrence imposed a surgical biopsy. A pigmented villonodular synovitis
      diagnosis was made, a rare vertebral pathology--around 50 reports, only 3
      concerning C1-C2 location. No further treatment was assigned precluding the
      iatrogenic consequences of empirical treatments based on clinical diagnosis with
      no histopathological support. The patient remains stable at 18 months of follow
      up. CONCLUSION: A large differential diagnosis should be made when the typical
      findings for metastatic disease are absent precluding the iatrogenic consequences
      of empirical treatments based on clinical diagnosis with no histopathological
      support.

PMID- 24908255
TI  - An efficient wavelet-based approximation method to gene propagation model arising
      in population biology.
AB  - In this paper, we have applied an efficient wavelet-based approximation method
      for solving the Fisher's type and the fractional Fisher's type equations arising
      in biological sciences. To the best of our knowledge, until now there is no
      rigorous wavelet solution has been addressed for the Fisher's and fractional
      Fisher's equations. The highest derivative in the differential equation is
      expanded into Legendre series; this approximation is integrated while the
      boundary conditions are applied using integration constants. With the help of
      Legendre wavelets operational matrices, the Fisher's equation and the fractional
      Fisher's equation are converted into a system of algebraic equations. Block-pulse
      functions are used to investigate the Legendre wavelets coefficient vectors of
      nonlinear terms. The convergence of the proposed methods is proved. Finally, we
      have given some numerical examples to demonstrate the validity and applicability
      of the method. 

PMID- 24908256
TI  - Function of the ligamentum teres in limiting hip rotation: a cadaveric study.
AB  - PURPOSE: The purpose of this cadaveric study was to evaluate the function of the
      ligamentum teres (LT) in limiting hip rotation in 18 distinct hip positions while
      preserving the capsular ligaments. METHODS: Twelve hips in 6 fresh-frozen pelvis
      to-toes cadaveric specimens were skeletonized from the lumbar spine to the distal
      femur, preserving only the hip ligaments. Hip joints were arthroscopically
      accessed through a portal located between the pubofemoral and iliofemoral
      ligaments to confirm the integrity of the LT. Three independent measurements of
      hip internal and external rotation range of motion (ROM) were performed in 18
      defined hip positions of combined extension-flexion and abduction-adduction. The
      LT was then arthroscopically sectioned and rotation ROM reassessed in the same
      positions. A paired sample t test was used to compare the average internal and
      external hip rotation ROM values in the intact LT versus resected conditions in
      each of the 18 positions. P < .0014 was considered significant. RESULTS: A
      statistically significant influence of the LT on internal or external rotation
      was found in 8 of the 18 hip positions tested (P < .0014). The major increases in
      internal and external rotation ROM occurred when the hip was in 90 degrees  or
      120 degrees  of flexion. CONCLUSIONS: The major function of the LT is controlling
      hip rotation. The LT functions as an end-range stabilizer to hip rotation
      dominantly at 90 degrees  or greater of hip flexion, confirming its contribution
      to hip stability. CLINICAL RELEVANCE: Ruptures of the LT contribute to hip
      instability dominantly in flexed hip positions.

PMID- 24908257
TI  - Knot impingement after rotator cuff repair: is it real?
AB  - PURPOSE: The purpose of this study was to compare morphologic features of the
      acromion after 2 different repair methods (single-row [SR] repair with a minimum
      of 4 knots and suture-bridge [SB] repair with minimal knots) in medium to large
      rotator cuff tears. METHODS: From May 2005 to July 2012, 1,693 rotator cuff
      repairs were performed, among them medium to large tears requiring more than 2
      anchors for repair; those who had 6-month postoperative magnetic resonance
      imaging (MRI) scans were included (221 shoulders). They were divided into 2
      groups; group A (SR repair) and group B (SB repair). Acromial morphologic
      characteristics were evaluated using MRI 6 months postoperatively. An acromial
      defect was defined as an irregular defect or erosion on the flat acromion.
      Clinical measurements were performed using the American Shoulder and Elbow
      Surgeons (ASES) score, Constant score, visual analogue scale (VAS) pain score,
      and range of motion (ROM). RESULTS: Erosion in the acromion was observed in 2 of
      118 patients (1.7%) in group A and in 1 of 103 (1%) patients in group B. There
      was no statistically significant difference between the 2 groups (P = .796). A
      statistically significant improvement was observed in the clinical scores
      measured (P = .0043). ROM was not fully recovered to the preoperative level at 6
      months postoperatively. Acromioplasty was performed in 2 of 3 patients with
      acromial erosion. There was acromial erosion in one patient in group A without
      performing subacromial decompression. CONCLUSIONS: Our study showed that there
      was no difference in acromial erosion in high-profile knots made by an SR
      compared with double-row (DR) SB low-profile repairs. LEVEL OF EVIDENCE: Level
      III, retrospective comparative study.

PMID- 24908258
TI  - Thermal fluctuations in artificial spin ice.
AB  - Artificial spin ice systems have been proposed as a playground for the study of
      monopole-like magnetic excitations, similar to those observed in pyrochlore spin
      ice materials. Currents of magnetic monopole excitations have been observed,
      demonstrating the possibility for the realization of magnetic-charge-based
      circuitry. Artificial spin ice systems that support thermal fluctuations can
      serve as an ideal setting for observing dynamical effects such as monopole
      propagation and as a potential medium for magnetricity investigations. Here, we
      report on the transition from a frozen to a dynamic state in artificial spin ice
      with a square lattice. Magnetic imaging is used to determine the magnetic state
      of the islands in thermal equilibrium. The temperature-induced onset of magnetic
      fluctuations and excitation populations are shown to depend on the lattice
      spacing and related interaction strength between islands. The excitations are
      described by Boltzmann distributions with their factors in the frozen state
      relating to the blocking temperatures of the array. Our results provide insight
      into the design of thermal artificial spin ice arrays where the magnetic charge
      density and response to external fields can be studied in thermal equilibrium. 

PMID- 24908259
TI  - Cultivation to improve in vivo solubility of overexpressed arginine deiminases in
      Escherichia coli and the enzyme characteristics.
AB  - BACKGROUND: Overexpression of foreign genes in Escherichia coli cells is an
      efficient means to obtain recombinant proteins. The technique is, however, often
      hampered by misfolding, degradation, aggregation and formation in inclusion
      bodies of products. RESULTS: In this study, we reported that in vivo solubility
      of overexpressed arginine deiminases (ADI) improved by changing the cultivation
      conditions. ADI is enzymes that convert L-arginine to L-citrulline. After codon
      optimization, we synthesized the ADI gene of Pseudomonas putida and constructed
      it for overexpression in E. coli cells. The rADI products were mainly in
      inclusion body forms. We performed a series of optimization to enhance solubility
      of the protein. Co-expression with the GroES-GroEL chaperone team increased
      approximately 5-fold of the rADI activity. In addition the combination of L
      arginine and D-glucose in the Luria-Bertani (LB) growth medium further increased
      the total activity to about 15 times. Separate L-arginine and D-glucose or the
      addition of other saccharides or amino acids had no such effects. The
      solubilization effects of the combination of L-arginine and D-glucose were
      further confirmed in the overexpression of another ADI from Listeria welshimeri.
      The enzymatic and conversion characteristics of the rADI products were further
      determined. CONCLUSIONS: Combined addition of L-arginine and D-glucose in the LB
      medium significantly improved in vivo solubility of rADI proteins. The present
      study suggested a new strategy to increase the solubilization of overexpressed
      recombinant proteins in E. coli cells.

PMID- 24908260
TI  - Health care utilization patterns and costs for patients with hidradenitis
      suppurativa.
AB  - IMPORTANCE: Hidradenitis suppurativa (HS) is a chronic cutaneous disease with
      acutely painful flares that require appropriate and timely treatment. OBJECTIVE:
      To assess how individuals with HS utilize medical care, especially emergency
      department (ED) care, a high-cost setting, and to describe the health care costs
      for this group. DESIGN, SETTING, AND PARTICIPANTS: Cohort cost-identification
      study of 150 493 individuals with claims from the MarketScan medical claims
      database. Patients with claims for HS and psoriasis (16 736 and 110 266,
      respectively) and a control group with neither condition (23 491) during the
      study period, January 2008 to December 2010, were included. EXPOSURES: An HS
      cohort was formed from all the patients who had 2 or more claims for HS
      (International Classification of Diseases, Ninth Revision [ICD-9] code 705.83)
      during the 3-year period. A psoriasis cohort was used as a comparison group,
      since it is another chronic inflammatory condition with prominent skin findings.
      This group included randomly selected patients who had 2 or more claims for
      psoriasis (ICD-9 code 696.1) during the 3-year period. A second control group
      included randomly selected patients who had no claims for either condition during
      the 3-year period. From these cohorts only patients that were continuously
      enrolled for the 3-year period were included. MAIN OUTCOMES AND MEASURES: Health
      care utilization measures including inpatient length of stay, emergency
      department and outpatient visits, and number of days supplied of prescription
      medication were investigated. Cost variables were also investigated and included
      inpatient, outpatient, emergency department, prescription drug, and total all
      cause health care expenditures, which were adjusted for inflation and reported in
      2010 US dollars. RESULTS: The largest component of the total 3-year cost for the
      HS group was inpatient cost (37.4%). In contrast, for the psoriasis group this
      was drug costs (46.5%) and for the control group, inpatient costs (40.9%). The
      proportion of people who were hospitalized in the HS cohort (15.8%) was higher
      than the psoriasis (10.8%) or control (8.6%) groups (P < .001). The proportion of
      patients who used the ED over the 3-year period was higher in the HS cohort
      (27.1%) than the psoriasis (17.4%) or control groups (17.2%) (P < .001).
      Similarly, the mean (SD) 3-year ED cost for the HS group was $2002 ($6632) and
      was higher than both comparison groups (P < .001). After adjustment for age, sex,
      and comorbidities, ED utilization remained higher in the HS group compared with
      the control (P < .001) and psoriasis (P = .02) cohorts. CONCLUSIONS AND
      RELEVANCE: Hidradenitis suppurativa affects a younger, predominantly female
      population of patients. High-cost settings, such as ED and inpatient care, are
      used more frequently for patients with HS. Both patients and clinicians should be
      aware of this finding, and further research is needed to investigate the impact
      of health care utilization on patient outcomes.

PMID- 24908261
TI  - Analysis of the smoke of cigarettes containing Salvia divinorum.
AB  - Salvia divinorum is a hallucinogen sold over the internet in several forms.
      Perhaps the most common method of use is smoking the dried leaf material. The
      sole presumed active constituent, salvinorin A, is a selective kappa-opioid
      receptor agonist. Upon smoking of the dried leaf material, some of the salvinorin
      A is destroyed or converted to other materials, leaving in question the actual
      amount of salvinorin A delivered that leads to the psychotomimetic effect. On
      average, 133 MUg of salvinorin A was delivered in the smoke from an 830 mg per
      cigarette, which contained ~2.7 mg of salvinorin A. Hence, only ~5% of the
      salvinorin A available in the dried plant material was delivered in the smoke.
      Upon smoking, hydrolysis of salvinorin A to salvinorin B, an inactive and minor
      component of the leaf material, also occurs as evidenced by a higher delivered
      amount of salvinorin B vs salvinorin A (217 vs 133 MUg per cigarette). Since
      smoking is an effective means of achieving the hallucinogenic effect and
      salvinorin A is the presumed sole active ingredient in the plant, the estimated
      effective dose of salvinorin A by inhalation is <133 MUg per person. Considering
      the reported rapid metabolism of salvinorin A in vivo, the dose reaching the
      brain would be substantially less. 

PMID- 24908262
TI  - Enzyme-linked immunosorbent assay (ELISA) for the detection of use of the
      synthetic cannabinoid agonists UR-144 and XLR-11 in human urine.
AB  - Ongoing changes in the synthetic cannabinoid drug market create the need for
      relevant targeted immunoassays for rapid screening of biological samples. We
      describe the validation and performance characteristics of an enzyme-linked
      immunosorbent assay designed to detect use of one of the most prevalent synthetic
      cannabinoids in urine, UR-144, by targeting its pentanoic acid metabolite.
      Fluorinated UR-144 (XLR-11) has been demonstrated to metabolize to this common
      product. The assay has significant cross-reactivity with UR-144-5-OH, UR-144-4-OH
      and XLR-11-4-OH metabolites, but <10% cross-reactivity with the parent compounds,
      and no measurable cross-reactivity with other synthetic cannabinoids and their
      metabolites at concentrations of <1,000 ng/mL. The assay's cutoff is 5 ng/mL
      relative to the pentanoic acid metabolite of UR-144, which is used as the
      calibrator. The method was validated with 90 positive and negative control urine
      samples for UR-144, XLR-11 and its metabolites tested versus liquid
      chromatography-tandem mass spectrometry. The accuracy, sensitivity and
      specificity were determined to be 100% for the assay at the specified cutoff. 

PMID- 24908263
TI  - Association between metabolic syndrome and osteoporotic fracture in middle-aged
      and elderly Chinese peoples.
AB  - Associations between metabolic syndrome (MetS) and osteoporotic fracture have
      been reported. However, the epidemiological studies are not conclusive. The
      objective of the study was to determine whether MetS associates with osteoporotic
      fracture. This was a cross-sectional study of 9,930 Chinese adults aged 40 years
      or older in the Chongming District, Shanghai, China. A questionnaire,
      anthropometric measurements and laboratory tests were conducted. Metabolic
      syndrome was defined according to the updated National Cholesterol Education
      Program Adult Treatment Panel III criteria for Asian Americans. A history of
      fractures was collected with an interviewer-assisted questionnaire. Osteoporotic
      fractures were defined as fractures that occurred due to low trauma in 2 years
      prior to the study. Among women, the prevalence of osteoporotic fractures was
      significantly higher in those with MetS (3.5 vs. 2.6 %, = 0.028). However, the
      difference was not found in men (2.6 vs. 2.4 %, P = 0.737). The presence of MetS
      was significantly associated with increased odds of osteoporotic fracture among
      women (odds ratio 1.22; 95 % confidence interval 1.12-1.54; P = 0.039) after
      controlling for potential confounders. The significant associations were not
      detected in men. The presence of MetS was significantly associated with a recent
      history of osteoporotic fracture in middle-aged and elderly Chinese women.

PMID- 24908264
TI  - Comparison of multi-slice computed tomographic angiography and dual-source
      computed tomographic angiography in resectability evaluation of pancreatic
      carcinoma.
AB  - The assessment of pancreatic cancer resectability is based mainly on the extent
      of the peripancreatic vasculature involvement with tumor mass. The 16-slice
      computed tomography (MSCT) and dual-source computed tomography (DSCT) were used
      in non-invasive imaging of the pancreas and the regional vessels in 48 pancreatic
      carcinoma patients. Both of these techniques were combined with contrast-enhanced
      angiography and post-scanning reconstruction of 2D and 3D images. Based on the
      degree of involvement revealed by these images, the pre-operative tumor
      resectability was determined. The CTA-based resectability was then correlated
      with the surgical and pathological findings for the evaluation of their
      sensitivity, specificity, negative and positive predictive values, and diagnostic
      accuracy. The study suggests that resectability based on dual-source CTA showed
      higher sensitivity, specificity, and diagnostic accuracy than that obtained from
      MSCTA scanning. 

PMID- 24908265
TI  - The clinical study of the optimalization of surgical treatment and the
      traditional Chinese medicine intervention on palmar hyperhidrosis.
AB  - To analyze the efficacy of different surgical methods in treating palmar
      hyperhidrosis and the compensatory hyperhidrosis after surgery and to observe the
      efficacy of "Energy-boosting and Yin-nourishing anti-perspirant formula" on
      postsurgical hyperhidrosis patients. Two-hundred patients were randomly assigned
      to groups A (Chinese and Western medicine, T4 transection plus "Energy-boosting
      and Yin-nourishing anti-perspirant formula") and B (Western medicine, T4
      transection). The surgical efficiency, recurrence rate, compensatory
      hyperhidrosis, and the long-term life quality were compared. Another 100 cases
      (group C, T2 transection) were analyzed as a control group. After surgery, the
      palmar hyperhidrosis and armpit sweating were relieved in all the three group
      patients and in 34 % of patients combined with plantar hyperhidrosis, the
      symptoms were relieved. Transient palmar hyperhidrosis was found in three cases
      at day 2 to day 5 postoperatively. One case of Horner's syndrome and one case
      recurrence were found in group C patients. The compensatory sweating of various
      degrees occurred in all the three groups. There were 25, 24, and 43 cases in
      groups A, B, and C, respectively. There is a significant difference between
      groups C, A, and B. The compensatory sweating in 13 cases of group A and four
      cases of group B had different degrees of improvement in the follow-up 6 months
      after surgery. There is a significant difference. Thoracoscopic bilateral T4
      sympathetic chain and the Kuntz resection are the optimized surgical treatments
      for the palmar hyperhidrosis. "Energy-boosting and Yin-nourishing anti-perspirant
      formula" is effective in treating the postoperative compensatory sweating.

PMID- 24908266
TI  - Reform of public hospitals and the main role of medical staffs.
AB  - The success of reforms to the public hospital system in China depends on the
      motivation and mobilization of medical staffs. Several factors are known to
      influence the motivation of health workers, including remuneration, acquisition
      of power and reputation, the ability to care for others, and the level of
      satisfaction. Obtaining recognition turns out to be a central factor in affecting
      motivation, while power and reputation fuel the health workers' enthusiasm.
      Providing caring for others and level of satisfaction safeguards the enthusiasm
      of medical staffs. We found that the motivation of medical staffs was enhanced
      through institutionalized programs that reward, empower, and promote the
      reputation of individuals, and other factors. Through the implementation of these
      programs, the medical staffs of Xuzhou Central Hospital have been successfully
      mobilized, resulting in an improvement in performance securing the healthy growth
      of the hospital, which ultimately translated to better health care delivery for
      the people in the region. 

PMID- 24908267
TI  - CONSTANS-LIKE 7 (COL7) is involved in phytochrome B (phyB)-mediated light-quality
      regulation of auxin homeostasis.
AB  - Arabidopsis phytochrome B (phyB) is the major photoreceptor that senses the ratio
      of red to far-red light (R:FR) to regulate the shade-avoidance response (SAR). It
      has been hypothesized that altered homeostasis of phytohormones such as auxin and
      strigolactone is at least partially responsible for SAR, but the mechanism
      underlying phyB regulation of the hormonal change is not fully understood.
      Previously we reported that CONSTANS-LIKE 7 (COL7) enhances branching number
      under high R:FR but not under low R:FR, implying that COL7 may be involved in the
      phyB-mediated SAR. In this study, we provide evidence that COL7 reduces auxin
      levels in a high R:FR-dependent manner. We found that the phyB mutation
      suppresses the COL7-induced branching proliferation. Moreover, COL7 promotes mRNA
      expression of SUPERROOT 2 (SUR2), which encodes a suppressor of auxin
      biosynthesis, in high R:FR but not in low R:FR. Consistently with these results,
      deficiency of phyB suppresses the elevated transcription of SUR2 in COL7
      overexpression plants grown in high R:FR. Taking these results together with data
      suggesting that photo-excited phyB is required for stabilization of the COL7
      protein, we argue that COL7 is a critical factor linking light perception to
      changes in auxin level in Arabidopsis. 

PMID- 24908268
TI  - Spatial H2O2 signaling specificity: H2O2 from chloroplasts and peroxisomes
      modulates the plant transcriptome differentially.
AB  - Hydrogen peroxide (H2O2) operates as a signaling molecule in eukaryotes, but the
      specificity of its signaling capacities remains largely unrevealed. Here, we
      analyzed whether a moderate production of H2O2 from two different plant cellular
      compartments has divergent effects on the plant transcriptome. Arabidopsis
      thaliana overexpressing glycolate oxidase in the chloroplast (Fahnenstich et al.,
      2008; Balazadeh et al., 2012) and plants deficient in peroxisomal catalase
      (Queval et al., 2007; Inze et al., 2012) were grown under non-photorespiratory
      conditions and then transferred to photorespiratory conditions to foster the
      production of H2O2 in both organelles. We show that H2O2 originating in a
      specific organelle induces two types of responses: one that integrates signals
      independently from the subcellular site of H2O2 production and another that is
      dependent on the H2O2 production site. H2O2 produced in peroxisomes induces
      transcripts involved in protein repair responses, while H2O2 produced in
      chloroplasts induces early signaling responses, including transcription factors
      and biosynthetic genes involved in production of secondary signaling messengers.
      There is a significant bias towards the induction of genes involved in responses
      to wounding and pathogen attack by chloroplastic-produced H2O2, including indolic
      glucosinolates-, camalexin-, and stigmasterol-biosynthetic genes. These
      transcriptional responses were accompanied by the accumulation of 4-methoxy-indol
      3-ylmethyl glucosinolate and stigmasterol. 

PMID- 24908270
TI  - A general theory of transition to addiction it was and a general theory of
      transition to addiction it is: reply to the commentaries of Ahmed, Badiani,
      George & Koob, Kalivas & Gipson, and Tiffany.

PMID- 24908271
TI  - Antipsychotic induced chronic recurrent oculogyric crisis in a patient with
      obsessive compulsive disorder.

PMID- 24908273
TI  - Metrical analysis of dromedary digital bones.
AB  - Dromedary camels are large even-toed ungulates which are well adapted to life in
      large deserts. Examinations of their feet have revealed many structural
      peculiarities. We have measured the digital bones of the dromedary in order to
      determine whether there are morphometric variations in the digital bones between
      the lateral and medial sides in individual limbs and/or in the right and left
      thoracic and pelvic limbs, with the aim to clarify whether there are anatomical
      differences in the digital bones of dromedary as a suborder of the order
      Artiodactyla. Measurements were made of 240 lateral and medial proximal, middle,
      and distal phalanges in the left and right thoracic and pelvic limbs of ten
      healthy adult male dromedaries, ranging in age from 6 to 10 years. A total of 17
      linear dimensions were measured using a caliper. The results indicate that there
      are no significant differences between corresponding measurements of digital
      bones of the lateral and medial in the same limb, nor between measurements of the
      right and left sides. The lengths and widths of the proximal and middle, and
      distal phalanges in the thoracic limb were found to be greater than those of the
      pelvic limb. The sum of the total lengths of the three phalanges of the thoracic
      limbs was 15 mm greater than that of the phalanges of the pelvic limbs due to a
      longer proximal phalanx (76 %) and middle phalanx of the former (24 %). The
      perspectives obtained by our morphometric study of dromedary digital bones not
      only provide a tool to distinguish the osteological remains of the dromedary from
      those of the Bactrian camel or other artiodactyls in archaeological sites, but
      they also suggest a possible influence of digital structure on digit functions
      and digital disorders.

PMID- 24908272
TI  - Higher sensitivity to the conditioned rewarding effects of cocaine and MDMA in
      High-Novelty-Seekers mice exposed to a cocaine binge during adolescence.
AB  - RATIONALE: Exposure to drugs during adolescence can induce alterations in the
      central nervous system. The novelty-seeking personality trait influences
      differences observed among individuals exposed to drugs of abuse. OBJECTIVES:
      Long-term effects of intensive pre-treatment with cocaine during adolescence or
      adulthood were evaluated in High- and Low-Novelty Seeker (HNS and LNS) mice. It
      was hypothesized that a cocaine binge during adolescence would increase
      sensitivity to the rewarding effects of cocaine and MDMA, especially in HNS
      animals, and modify the spontaneous behaviour of adult animals. METHODS:
      Adolescent (PND 33) and adult (PND 60) mice were identified as HNS or LNS
      according to their performance in the hole-board test. Subsequently, they
      received pre-treatment with cocaine (three injections per day of an increasing
      dose for 10 days) or saline. Three weeks later, the mice performed the hole
      board, elevated plus maze, spontaneous locomotor activity and cocaine- (1 mg/kg)
      or MDMA- (1.25 mg/kg) induced conditioning place preference (CPP) tests. In
      another set of mice, the effects of pre-treatment of cocaine during adulthood on
      MDMA- or cocaine-induced CPP were also evaluated 3 weeks later. RESULTS: Only HNS
      mice treated with cocaine during adolescence acquired MDMA- or cocaine-induced
      CPP in adulthood. Moreover, pre-exposure to cocaine during adolescence caused
      subsequent behavioural alterations, including reduced exploratory behaviour and
      increased locomotor reactivity. CONCLUSIONS: Cocaine binge administration during
      adolescence induces a higher sensitivity to the rewarding effects of MDMA and
      cocaine in HNS mice in adulthood. This may explain the greater vulnerability
      often seen among individuals exposed early in life to drugs of abuse.

PMID- 24908274
TI  - The clinical significance of Cyniclomyces guttulatus in dogs with chronic
      diarrhoea, a survey and a prospective treatment study.
AB  - This study surveyed the prevalence of massive numbers of Cyniclomyces guttulatus
      in faecal samples from healthy dogs (18%) and dogs with chronic diarrhoea (14%)
      suggesting that this yeast has no clinical significance. Subsequently, a total of
      57 referred dogs with chronic diarrhoea were selected because they excreted
      massive numbers of C. guttulatus and their initial diagnostic work-up yielded no
      other direct clues explaining their diarrhoea. Treatment with nystatin did not
      result in any clinical response in 36 out of these 57 dogs (63%), although they
      no longer shed the yeast. However, a response was noted in the remaining 21 (37%)
      dogs: 13 were 'responders', in that their diarrhoea subsided for more than two
      weeks and the faeces were cleared of the yeast. However, three of these dogs
      relapsed repeatedly, with signs of diarrhoea and massive shedding of the yeast.
      The other eight dogs were 'incomplete responders', whereby faecal quality
      initially normalised, but diarrhoea relapsed within two weeks, whilst still not
      shedding the yeast. In these cases, further diagnostic work up revealed other co
      causes of diarrhoea. It was concluded that there was no direct evidence that C.
      guttulatus is a primary pathogen. However, the results of the prospective
      treatment study suggest that a possible role in a minority of cases, perhaps as
      an opportunist, cannot be ruled out. 

PMID- 24908275
TI  - Molecular characterization of Belgian pseudorabies virus isolates from domestic
      swine and wild boar.
AB  - Aujeszky's disease is an economically important disease in domestic swine caused
      by suid herpesvirus 1, also called pseudorabies virus (PRV). In several European
      countries, including Belgium, the virus has successfully been eradicated from the
      domestic swine population. The presence of PRV in the wild boar population
      however poses a risk for possible reintroduction of the virus into the domestic
      pig population. It is therefore important to assess the genetic relatedness
      between circulating strains and possible epidemiological links. In this study,
      nine historical Belgian domestic swine isolates that circulated before 1990 and
      five recent wild boar isolates obtained since 2006 from Belgium and the Grand
      Duchy of Luxembourg were genetically characterized by restriction fragment length
      polymorphism (RFLP) analysis and phylogenetic analysis. While all wild boar
      isolates were characterized as type I RFLP genotypes, the RFLP patterns of the
      domestic swine isolates suggest that a shift from genotype I to genotype II might
      have occurred in the 1980s in the domestic population. By phylogenetic analysis,
      Belgian wild boar isolates belonging to both clade A and B were observed, while
      all domestic swine isolates clustered within clade A. The joint phylogenetic
      analysis of both wild boar and domestic swine strains showed that some isolates
      with identical sequences were present within both populations, raising the
      question whether these strains represent an increased risk for reintroduction of
      the virus into the domestic population. 

PMID- 24908276
TI  - Experimental infection of sheep and goats with a recent isolate of peste des
      petits ruminants virus from Kurdistan.
AB  - Peste des petits ruminants (PPR) is a contagious viral disease of sheep and goats
      common in Africa and Asia. Its high morbidity and mortality has a devastating
      impact on agriculture in developing countries. As an example, an Asian lineage IV
      strain of PPRV was responsible for mass fatalities among wild goats in Kurdistan
      in 2010/2011. In separate experiments, three sheep and three goats of German
      domestic breeds were subcutaneously inoculated with the Kurdish virus isolate;
      three uninfected sheep and goats were housed together with the inoculated
      animals. All inoculated animals, all in-contact goats and two in-contact sheep
      developed high fever (up to 41.7  degrees C), depression, severe diarrhea, ocular
      and nasal discharge as well as ulcerative stomatitis and pharyngitis. Infected
      animals seroconverted within a few days of the first detection of viral genome.
      Clinical signs were more pronounced in goats; four out of six goats had to be
      euthanized. Necropsy revealed characteristic lesions in the alimentary tract.
      Peste des petits ruminants virus (PPRV) RNA was detected in blood as well as
      nasal, oral and fecal swabs and tissues. The 2011 Kurdish strain of PPRV is
      highly virulent in European goats and spreads easily to in-contact animals, while
      disease severity and contagiosity in sheep are slightly lower. PPRV strains like
      the tested recent isolate can have a high impact on small ruminants in the
      European Union, and therefore, both early detection methods and intervention
      strategies have to be improved and updated regularly.

PMID- 24908278
TI  - Pleomorphic adenoma presenting with conductive hearing loss in the ear canal: a
      case report and review of the literature.
AB  - INTRODUCTION: Pleomorphic adenoma accounts for 65 percent of all salivary gland
      tumors. It has been identified in several anatomical regions, but pleomorphic
      adenoma arising in the ear canal, first described in 1951, is extremely rare.
      CASE PRESENTATION: A 40-year-old Japanese man's left ear canal was obstructed by
      a pleomorphic adenoma that caused mild conductive hearing loss. The tumor was
      resected and he remains disease-free two years after surgery. CONCLUSIONS:
      Pleomorphic adenoma usually arises from a major and minor salivary gland, but
      pleomorphic adenoma of the ear canal is derived from the ceruminous gland. We
      discuss the present case and 37 other case reports in our effort to clarify the
      clinical features and the course of pleomorphic adenoma in the ear canal.

PMID- 24908277
TI  - Sequencing of diverse mandarin, pummelo and orange genomes reveals complex
      history of admixture during citrus domestication.
AB  - Cultivated citrus are selections from, or hybrids of, wild progenitor species
      whose identities and contributions to citrus domestication remain controversial.
      Here we sequence and compare citrus genomes--a high-quality reference haploid
      clementine genome and mandarin, pummelo, sweet-orange and sour-orange genomes-
      and show that cultivated types derive from two progenitor species. Although
      cultivated pummelos represent selections from one progenitor species, Citrus
      maxima, cultivated mandarins are introgressions of C. maxima into the ancestral
      mandarin species Citrus reticulata. The most widely cultivated citrus, sweet
      orange, is the offspring of previously admixed individuals, but sour orange is an
      F1 hybrid of pure C. maxima and C. reticulata parents, thus implying that wild
      mandarins were part of the early breeding germplasm. A Chinese wild 'mandarin'
      diverges substantially from C. reticulata, thus suggesting the possibility of
      other unrecognized wild citrus species. Understanding citrus phylogeny through
      genome analysis clarifies taxonomic relationships and facilitates sequence
      directed genetic improvement.

PMID- 24908279
TI  - Association between allopurinol and mortality among Japanese hemodialysis
      patients: results from the DOPPS.
AB  - PURPOSE: Allopurinol, for treating hyperuricemia, is associated with lower
      mortality among hyperuricemic patients without chronic kidney disease (CKD).
      Greater allopurinol utilization in hemodialysis (HD) in Japan versus other
      countries provides an opportunity for understanding allopurinol-related HD
      outcomes. METHODS: Data from 6,252 Japanese HD patients from phases 1-3 of the
      Dialysis Outcomes and Practice Patterns Study (1999-2008) at ~60 facilities per
      phase were analyzed. Mortality was compared for patients prescribed (25 %) versus
      not-prescribed allopurinol using Cox regression, overall, and in patient
      subgroups. RESULTS: Patients prescribed allopurinol were more likely to be
      younger, male, and non-diabetic, and had higher serum creatinine and lower
      (treated) serum uric acid levels (mean = 7.0 vs. 8.0 mg/dL, p < 0.001). The
      inverse association between allopurinol prescription and mortality in unadjusted
      analyses (HR 0.65, 95 % CI 0.52-0.81) was attenuated by covariate adjustment (HR
      0.84, 0.66-1.06). In subgroup analyses, allopurinol was associated with lower
      mortality among patients with no history of cardiovascular disease (CVD) (HR
      0.48, 0.28-0.83), but not among patients with CVD (HR 1.00, 0.76-1.32). A similar
      pattern was seen outside Japan and for cardiovascular (CV)-related mortality.
      CONCLUSIONS: Allopurinol prescription was not significantly associated with case
      mix-adjusted mortality in Japanese HD patients overall, but was associated with
      lower all-cause and CV-related mortality in the subgroup of patients with no
      prior CVD history. These findings in HD patients may be related to findings in
      non-dialysis CKD patients showing lower CV event rates and mortality, and
      improved endothelial function with allopurinol prescription. These results are
      useful for designing future trials of allopurinol use in HD patients.

PMID- 24908280
TI  - Correlation study of chronic nonbacterial prostatitis with the levels of COX-2
      and PGE2 in prostatic secretion.
AB  - OBJECTIVE: The prostatitis syndrome is a multifactorial condition of largely
      unknown etiology. This study is to analyze the relationship between
      cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) with the chronic
      nonbacterial prostatitis (CNBP). METHODS: A total of 172 CNBP patients and 151
      healthy males were recruited as CNBP and control group, respectively. The
      prostatic fluid was collected and tested by pre- and post-massage test. White
      blood cell (WBC) number was counted, and the contents of COX-2 and PGE2 were
      determined by double antibody-based sandwich enzyme-linked immuno-sorbent assay.
      The pain and discomfort of each patient were scored according to the National
      Institutes of Health chronic prostatitis symptom index. RESULTS: Compared with
      the control group, CNBP group displayed significantly higher WBC count, COX-2
      level, and PGE2 level. Contents of COX-2 and PGE2 in prostatic secretion of CNBP
      group were positively correlated with pain scores (r = 0.855 and 0.675,
      respectively, P < 0.01) and total symptom scores (r = 0.674 and 0.566,
      respectively, P < 0.01). A significantly positive correlation between COX-2 and
      PGE2 levels was also discovered (r = 0.493, P < 0.05). The WBC number was not
      obviously correlated with the accumulations of COX-2 and PGE2 or the clinic
      symptoms of CNBP. CONCLUSION: Increase in PGE2 concentration caused by activated
      COX-2 pathway may contribute to the pain or discomfort symptom of the CNBP
      patients. Our results indicate that selective COX-2 inhibitors have application
      prospect in CNBP treatment.

PMID- 24908282
TI  - Cyclosporin A-induced posterior reversible encephalopathy syndrome in an
      adolescent with steroid-resistant nephrotic syndrome.

PMID- 24908283
TI  - A novel sodium-glucose co-transporter 2 gene (SGLT2) mutation contributes to the
      abnormal expression of SGLT2 in renal tissues in familial renal glucosuria.

PMID- 24908281
TI  - Associations between serum hepcidin level, FGF-21 level and oxidative stress with
      arterial stiffness in CAPD patients.
AB  - BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (CAPD) and
      hemodialysis have accelerated atherosclerosis associated with an increase in
      cardiovascular morbidity and mortality. Atherosclerosis is associated with
      increased arterial stiffness (AS), endothelial dysfunction and elevated oxidative
      stress (OS) and inflammation. We aimed to investigate the relationship between
      oxidative stress status, arterial stiffness, hepcidin and fibroblast growth
      factor-21 (FGF-21) levels in CAPD patients. METHODS: As a prospective
      observational study, we analyzed 56 CAPD patients, aged between 30 and 63 years.
      Serum hepcidin, FGF-21 levels, OS status and AS were determined. Arterial
      stiffness was measured by flow-mediated dilatation (FMD). Oxidative stress status
      was determined by total antioxidant status, total oxidant status (TOS) and
      oxidative stress index (OSI). RESULTS: FMD was negatively correlated with TOS,
      OSI, hepcidin and FGF-21 (r: -0.313, p: 0.020; r: -0.0331, p: 0.014; r: -0.498, p
      < 0.001; r: -0.403, p: 0.002, respectively). OSI was positively correlated with
      hepcidin, parathormone and negatively correlated with FMD (r: 0.278, p: 0.040; r:
      0.462, p < 0.001; r: -0.0331, p: 0.014, respectively). CONCLUSION: There are many
      factors affecting arterial stiffness in CAPD patients. In our study, higher
      levels of OS status, hepcidin and FGF-21 were independent determinants of
      arterial stiffness in PD patients. Therefore, definition and improvement of these
      new parameters will be helpful to reduce the cardiovascular disease risk and
      mortality in CAPD patients.

PMID- 24908284
TI  - The impact of abdominal aortic calcification and visceral fat obesity on lower
      urinary tract symptoms in patients with benign prostatic hyperplasia.
AB  - OBJECTIVES: To investigate the impact of abdominal aortic calcification and
      visceral fat area (VFA) on lower urinary tract symptoms (LUTS) and clinical
      parameters in patients with benign prostatic hyperplasia (BPH). METHODS: We
      retrospectively studied 250 patients with LUTS associated with BPH. Each
      participant was examined with routine examination including measurement of
      various data; (1) voided volume (VV), maximum urinary flow rate on free
      uroflowmetry, (2) postvoid residual urine volume and prostate volume using
      transabdominal ultrasound, (3) International Prostate Symptom Score (IPSS) and
      Overactive Bladder Symptom Score (OABSS), and (4) aortic calcification index
      (ACI) and VFA were measured by abdominal CT. RESULTS: Mean age of the patients
      was 72.4 +/- 9.6 years. ACI significantly correlated with VV (P = 0.0392) and
      tended to correlate with maximum urinary flow rate, while ACI did not correlate
      with subjective symptoms. VFA significantly correlated with nocturia score of
      IPSS (P = 0.0177) and frequency score of OABSS (P = 0.0166) and tended to
      correlate with urgency score of IPSS and maximum urinary flow rate. CONCLUSIONS:
      Aortic calcification index (ACI) correlated with only objective parameters, while
      VFA correlated with only storage symptoms. This study suggested that abdominal
      aortic calcification and VFA have certain influence on LUTS and clinical
      parameters in patients with BPH.

PMID- 24908285
TI  - Oral cavity squamous cell carcinoma: role of pretreatment imaging and its
      influence on management.
AB  - Squamous cell carcinoma (SCC) is the commonest malignancy in the oral cavity. The
      oral cavity has several subsites. Knowledge of the patterns of disease spread at
      each subsite with the impact on treatment and prognosis provides a deeper
      understanding of the role of imaging. Information from imaging helps accurate
      staging, assess resectability, and plan multimodality treatment. Mandibular
      erosion, posterior soft tissue extent, and perineural spread influence treatment
      and prognosis in gingival, buccal, and retromolar trigone (RMT) cancers.
      Multidetector computed tomography (MDCT) with multiplanar reformations and bone
      and soft tissue algorithms provides the highest specificity for bone erosion.
      Hard palate SCC is optimally imaged with contrast-enhanced magnetic resonance
      imaging (MRI) to detect perineural spread. In oral tongue and floor of the mouth
      (FOM) SCC, extrinsic muscle invasion, extension across the midline, extent of
      posterior and inferior spread, and proximity to the hyoid are issues that impact
      therapeutic options. Contrast-enhanced MRI is the optimal imaging method for
      staging the primary due to its superior soft tissue resolution. In oral tongue
      SCCs with tumour thickness <=4 mm, elective neck dissection can be avoided. For
      nodal staging (N-staging), all imaging methods are comparable, but fall short of
      surgical staging. Sentinel lymph node biopsy has a promising role in N-staging.
      Positron emission tomography (PET)/integrated PET/CT has no role in evaluating
      the clinically negative neck. PET/CT has a role in pretreatment evaluation of
      advanced oral cavity SCC for depicting distant metastases and for mapping nodal
      extent in the clinically positive neck. Diffusion-weighted MRI, dynamic contrast
      enhanced MRI, and CT perfusion have a potential role as baseline pretreatment
      studies for response assessment to chemoradiation in advanced oral cavity SCC. 

PMID- 24908286
TI  - Long-term effects of oral clefts on health care utilization: a sibling
      comparison.
AB  - Oral clefts are among the most common birth defects affecting thousands of
      newborns each year, but little is known about their potential long-term
      consequences. In this paper, we explore the impact of oral clefts on health care
      utilization over most of the lifespan. To account for time-invariant unobservable
      parental characteristics, we compare affected individuals with their own
      unaffected siblings. The analysis is based on unique data comprising the entire
      cohort of individuals born with oral clefts in Denmark tracked until adulthood in
      administrative register data. We find that children with oral clefts use more
      health services than their unaffected siblings. Additional results show that the
      effects are driven primarily by congenital malformation-related hospitalizations
      and intake of anti-infectives. Although the absolute differences in most health
      care utilization diminish over time, affected individuals have slightly higher
      utilization of some health care services in adulthood (particularly for diseases
      of the nervous and respiratory system). These results have important implications
      for affected individuals, their families, and their health professionals. 

PMID- 24908287
TI  - Next generation sequencing in cardiomyopathy: towards personalized genomics and
      medicine.
AB  - Next generation sequencing (NGS) is perhaps one of the most exciting advances in
      the field of life sciences and biomedical research in the last decade. With the
      availability of massive parallel sequencing, human DNA blueprint can be decoded
      to explore the hidden information with reduced time and cost. This technology has
      been used to understand the genetic aspects of various diseases including
      cardiomyopathies. Mutations for different cardiomyopathies have been identified
      and cataloging mutations on phenotypic basis are underway and are expected to
      lead to new discoveries that may translate to novel diagnostic, prognostic and
      therapeutic targets. With ease in handling NGS, cost effectiveness and fast data
      output, NGS is now considered as a diagnostic tool for cardiomyopathy by
      providing targeted gene sequencing. In addition to the number of genetic variants
      that are identified in cardiomyopathies, there is a need of quicker and easy way
      to screen multiple genes associated with the disease. In this review, an attempt
      has been made to explain the NGS technology, methods and applications in
      cardiomyopathies and their perspective in clinical practice and challenges which
      are to be addressed. 

PMID- 24908288
TI  - Expression analysis of KAP9.2 and Hoxc13 genes during different cashmere growth
      stages by qRT-PCR method.
AB  - Keratin-associated protein 9.2 (KAP9.2) and Homeobox C13 (Hoxc13) genes were
      chosen to study because of their biological functions involving hair formation.
      KAP9.2 gene belongs to the ultra high sulfur KAPs, which is important for hair
      formation and may have association with cashmere. Hoxc13 takes part in the
      formation of cashmere keratin and maintaining the normal structure of follicle.
      It has been reported that Hoxc13 gene exists binding site of KP and KAP genes at
      its promoter regions in mouse. So the expression of KAP9.2 and Hoxc13 genes was
      detected at anagen stage vs telogen stage by qRT-PCR. The data showed that KAP9.2
      and Hoxc13 gene had similar expression trend at different stages, which indicated
      that there was interaction between them. KAP9.2 and Hoxc13 gene had lower
      expression level in anagen than that of in telogen of cashmere growth. In anagen,
      KAP9.2 and Hoxc13 expressed lower in high cashmere yield individuals than that of
      in low cashmere yield ones. In telogen, the result was reverse. The study would
      provide the evidence of involvement of KAP9.2 and Hoxc13 in hair periodic growth.

PMID- 24908289
TI  - Brains are not just neurons. Comment on "Toward a computational framework for
      cognitive biology: unifying approaches from cognitive neuroscience and
      comparative cognition" by Fitch.

PMID- 24908290
TI  - The challenge of measuring elusive immune markers by enzyme-linked immuno-spot
      (ELISPOT) technique.
AB  - The enzyme-linked immuno-spot (ELISPOT) technique is a sensitive method used for
      measurement of elusive immune markers in limited-volume samples. By virtue of the
      exquisite sensitivity of the ELISPOT assay, frequency analysis of rare cell
      populations (e.g., antigen-specific responses), which was not possible before, is
      now relatively easy. However, development of a method sensitive enough to
      pinpoint elusive immune markers at the single-cell level is a challenge since
      there are a number of demands that have to be fulfilled and traps to avoid,
      achieving a valuable outcome.To optimize the environment for in vitro culture and
      analysis of immune spots by ELISPOT, a number of criteria have to be fulfilled:
      processing of sample and perhaps also cryopreservation of cells before analysis
      and, for the ELISPOT assay, optimal cell culture, positive and negative controls,
      antigen concentration, and, finally, development and readout of spots.If these
      criteria are fulfilled for your ELISPOT assay, you will likely have the
      opportunity to pinpoint elusive immune markers at the single-cell level. This
      chapter describes the ELISPOT assay for detection of cytokines (e.g., IFN-gamma
      and IL-4), with focus on the main criteria that affect the assay. However, this
      method could be easily adapted to measure other immune markers in small volumes
      of biological samples. 

PMID- 24908291
TI  - Analysis of the released nuclear cytokine HMGB1 in human serum.
AB  - A ubiquitous nuclear protein, the high-mobility group box 1 (HMGB1), is secreted
      by activated macrophages/monocytes and leaked passively from injured cells. HMGB1
      functions as a mediator of infection- and injury-elicited inflammatory diseases.
      Here, we describe a semiquantitative immuno-blotting method to measure the
      released HMGB1 in human serum, in comparison with a commercially available HMGB1
      ELISA technique.

PMID- 24908292
TI  - ELISA-based assay for IP-10 detection from filter paper samples.
AB  - IP-10 is a small pro-inflammatory chemokine secreted primarily from monocytes and
      fibroblasts. Alterations in IP-10 levels have been associated with inflammatory
      conditions including viral and bacterial infections, immune dysfunction, and
      tumor development. IP-10 is increasingly recognized as a biomarker that predicts
      severity of various diseases and can be used in the immunodiagnostics of
      Mycobacterium tuberculosis and cytomegalovirus infection. Here, we describe an
      ELISA-based method to detect IP-10 from dried blood and plasma spot samples. 

PMID- 24908293
TI  - Enhanced ELISA based on carboxymethylated dextran coatings.
AB  - In a "sandwich" enzyme-linked immunosorbent assay (ELISA) designed to detect an
      antigen in a complex protein mixture, the antigen is usually captured via an
      antibody adsorbed to the wells of a microplate. Plate preparation for standard
      assay involves a passive adsorption of capture antibodies followed by the
      incubation of blocking agents. Here, we describe a new strategy that replaces
      these two time-consuming adsorption steps (up to 15 h) by a unique step
      corresponding to the covalent grafting of the capture antibody on a
      carboxymethylated dextran (CMD) layer, a single step completed in 15 min. Taking
      advantage of the CMD low-fouling properties, blocking agent-free buffer solutions
      can be used as diluent in the improved approach. 

PMID- 24908294
TI  - A novel three-dimensional biosensor based on aluminum oxide: application for
      early-stage detection of human interleukin-10.
AB  - Immunosensors based on electrolyte-oxide-semiconductors (EOS) have been
      extensively researched over the last few decades. By electrochemical impedance
      spectroscopy (EIS) the specific molecular biorecognition of the antibody-antigen
      (Ab-Ag) can be detected providing an alternative quantitative system to
      immunoassay techniques. The electrochemical variations from a fabricated
      immunosensor can provide quantitative values for the analyte of interest at
      reduced costs and analysis time. In this context, a novel EOS substrate based on
      aluminum oxide (Al2O3) grown by atomic layer deposition on silicon was applied.
      The interaction between recombinant human (rh) interleukin-10 (IL-10) with the
      corresponding monoclonal antibody (mAb) for early cytokine detection of an anti
      inflammatory response due to left ventricular assisted device implantation was
      studied. For this purpose, a 3D biosensor was composed of multi-walled carbon
      nanotubes with carboxylic acid functionalities (multi-walled carbon nanotubes
      COOH) to increase the surface area for the range of human IL-10 detection. These
      were activated with N-hydroxysuccinimide and N-(3-dimethylaminopropyl)-N'-ethyl
      carbodiimide hydrochloride for the immobilization of the anti-human IL-10 mAb.
      First, the interaction between the Ab and Ag was observed by fluorescence
      patterning to ensure that the biorecognition event was achievable. Then, EIS is
      explained for the quantification of commercial human IL-10 on this capacitance
      based EOS macroimmuno-FET sensor.

PMID- 24908295
TI  - Quantification of multiple cytokines and chemokines using cytometric bead arrays.
AB  - Quantitative suspension array technology allows the simultaneous measurement of
      different cytokines and chemokines in small sample volumes. The possibility of
      measuring multiple variables is important for discovery of biomarkers of
      pathogenesis or protection in complex diseases as well as measurement of antigen
      specific cellular responses. Measurements can be made in biological specimens,
      such as plasma or serum, cell culture supernatants, and others. This technology
      is based on a capture-detection sandwich-type assay using fluorescent
      microspheres analyzable by Luminex instruments or flow cytometers. The complexity
      and cost of producing highly multiplexed cytokine/chemokine in-house assays make
      them especially apt for commercial production. There are several commercial kits
      available that vary in absolute cytokine concentration, sensitivity,
      reproducibility, and cost. This chapter gives an overview of cytometric bead
      array technology, introduces some of the kits, and provides detailed information
      about the one that performed well in a comparative study (Cytokine Human Magnetic
      30-Plex Panel from Life TechnologiesTM).

PMID- 24908296
TI  - A useful guide for analysis of immune markers by fluorochrome (Luminex)
      technique.
AB  - The fluorochrome Luminex technique is a bead-based sandwich immunoassay that
      combines the enzyme-linked immuno sorbent assay (ELISA) with flow cytometry. The
      Luminex technique allows multiple cytokines to be measured simultaneously in
      small volumes and provides a convenient and sensitive tool for the detection of a
      large number of, e.g., extracellular secreted cytokines to characterize cytokine
      profiles.The technique is based on the so-called microspheres (beads) that serve
      as a solid phase for molecular detection. These individually dyed micro-beads
      have monoclonal antibodies directed against the cytokines and chemokines of
      interest and allow simultaneous detection of up to nearly 100 cytokines and
      chemokines in a dual-laser flow analyzer. Immune markers can be detected in serum
      and plasma samples as well as in cell culture supernatants from in vitro
      stimulated peripheral blood mononuclear cells (PBMC).This chapter describes the
      Luminex technique for detection of multiple cytokines by magnetic bead sandwich
      immunoassay, with a special focus on some important pre-analytical factors, such
      as cell separation, cryopreservation, and PBMC thawing that may affect the
      detection outcome of immune markers. This method can also be easily adapted to
      measuring other biomarkers in biological samples. 

PMID- 24908297
TI  - Control of pro-inflammatory cytokine release from human monocytes with the use of
      an interleukin-10 monoclonal antibody.
AB  - The monocytes (MONOs) can be considered as "double-edge swords"; they have both
      important pro-inflammatory and anti-inflammatory functions manifested in part by
      cytokine production and release. Although MONOs are circulating cells, they are
      the major precursors of a variety of tissue-specific immune cells such as the
      alveolar macrophage, dendritic cells, microglial cells, and Kupffer cells. Unlike
      the polymorphonuclear leukocyte, which produces no or very little interleukin-10
      (IL-10), the monocyte can produce this potent anti-inflammatory cytokine to
      control inflammation. IL-10, on an equimolar basis, is a more potent inhibitor of
      pro-inflammatory cytokines produced by monocytes than many anti-inflammatory
      glucocorticoids which are used clinically. This chapter describes how to isolate
      monocytes from human blood and the use of IL-10 monoclonal antibody to determine
      the effect and timing of endogenous IL-10 release on the production and release
      of pro-inflammatory cytokines.

PMID- 24908298
TI  - Cytokine-induced neutrophil chemotaxis assay.
AB  - Chemotaxis is directed migration of a cell type to a distant chemoattractant.
      When this chemoattractant is a cytokine, the term chemokine is often used.
      Chemotaxis by neutrophils, specifically polymorphonuclear leukocytes (PMNs),
      plays a critical role in the innate immune response. On an equimolar basis,
      interleukin-8 (IL-8) is one of the most potent PMN chemokines known. This chapter
      describes an in vitro chemotaxis technique using PMNs and IL-8 which can serve
      the investigator as an established model from which new studies can be developed.

PMID- 24908299
TI  - An in vitro one-dimensional assay to study growth factor-regulated tumor cell
      macrophage interaction.
AB  - Growth factor-dependent pairing and motility between tumor cells and tumor
      associated macrophages on extracellular matrix (ECM) fibers of the tumor
      microenvironment have been shown to enhance intravasation and metastatic spread
      of breast carcinomas. We describe an in vitro motility assay that combines time
      lapse wide-field microscopy and micro-patterned linear adhesive substrates to
      reconstitute the in vivo behavior between macrophages, tumor cells, and ECM
      fibers in orthotopic rodent tumor models observed by intravital imaging.
      Commercially available linear stripes of 650 nm dye-labeled fibronectin
      microlithographed onto glass cover slips are sequentially plated with
      fluorescently labeled MTLn3 tumor cells and bone marrow-derived macrophages and
      time-lapse imaged for up to 8 h. Incubation with pharmacological inhibitors
      during the assay can identify important paracrine or autocrine signaling pathways
      involved in the macrophage-tumor cell interaction. This high-resolution motility
      assay will lead to a more detailed description of immune cell-tumor cell behavior
      as well as interrogating additional cell types within the tumor microenvironment
      which use cytokine/growth factor paracrine signaling interactions to facilitate
      intravasation and metastasis.

PMID- 24908300
TI  - Chemotactic responses by macrophages to a directional source of a cytokine
      delivered by a micropipette.
AB  - Macrophages, which are organized throughout every tissue, represent a key
      component of the immune system and the recruitment of macrophages to specific
      sites is important in normal host defense. However, when inappropriately
      recruited macrophages may damage or destroy healthy tissue; this is seen in
      several autoimmune diseases such as arthritis. Many cytokines, including CSF-1
      and chemokines, are often upregulated in inflamed tissues and can induce the
      directional migration of macrophages towards the highest concentration of the
      cytokine in a process called chemotaxis. Chemokines were first described as
      chemoattractant cytokines synthesized at sites of inflammation that stimulate the
      directional migration of leukocytes and mediate inflammation. Whereas specific
      receptors for chemoattractants reside over the entire cell surface, macrophages
      can detect very shallow chemotactic gradients leading to spatially defined
      responses to the chemoattractant such as the extension of directed protrusions
      leading to cell migration. In this chapter we describe a method for the localized
      delivery of chemoattractants via a micropipette needle to macrophages in culture
      followed by methods for imaging and an outline of quantifying macrophage
      responses. 

PMID- 24908301
TI  - Assessment of phagocytic activity of cultured macrophages using fluorescence
      microscopy and flow cytometry.
AB  - Phagocytosis is the process by which phagocytes, including macrophages,
      neutrophils and monocytes, engulf and kill invading pathogens, remove foreign
      particles, and clear cell debris. Phagocytes and their ability to phagocytose are
      an important part of the innate immune system and are critical for homeostasis of
      the host. Impairment in phagocytosis has been associated with numerous diseases
      and disorders. Different cytokines have been shown to affect the phagocytic
      process. Cytokines including TNFalpha, IL-1beta, GM-CSF, and TGF-beta1 were found
      to promote phagocytosis, whereas high mobility group box-1 (HMGB1) inhibited the
      phagocytic function of macrophages. Here, we describe two commonly used methods
      to assess the phagocytic function of cultured macrophages, which can easily be
      applied to other phagocytes. Each method is based on the extent of engulfment of
      FITC-labeled latex minibeads by macrophages under different conditions.
      Phagocytic activity can be assessed either by counting individual cells using a
      fluorescence microscope or measuring fluorescence intensity using a flow
      cytometer.

PMID- 24908302
TI  - Assessment of cytokine-modulated proteasome activity.
AB  - This chapter presents two methods for assessment of proteasome function. The
      first is a modification of the standard fluorogenic peptide cleavage assay which
      takes into account the effect of ATP on proteasome activity. This method is
      described in both its macro and high throughput micro-assay forms. The second is
      the Proteasome Constitutive Immuno-Subunit (active site) ELISA or ProCISE method.
      ProCISE is a modification of active site directed probe analysis and allows for
      convenient differentiation between active constitutive and immuno-subunits. While
      the utility of measuring proteasome activity and its relationship to cytokine
      action and inflammation are clear, the assessment and interpretation is not
      always straightforward. Therefore, we also discuss the pitfalls of the standard
      fluorogenic assay, particularly in the interpretation of results obtained, and
      the advantages of the newer, ProCISE assay. 

PMID- 24908303
TI  - Evaluation of the adverse effect of low concentration of cadmium on interleukin-4
      induced class switch recombination in Burkett's lymphoma Raji cell line.
AB  - Affinity maturation of B lymphocytes, a process that includes somatic
      hypermutation and class switch recombination, initiates global DNA
      rearrangements. The interruption of this process has an adverse effect on human
      health and results in immunodeficiency and autoimmune disease. Class switch
      recombination is a fundamental factor of the human adaptive immunity. Evaluation
      of the class switch recombination efficiency is an important component of
      laboratory diagnostic of immunotoxic components. Here, we describe a method for
      testing the efficiency of the class switch recombination. Cultivation of Raji
      Burkett's lymphoma cell line with anti-CD40 antibodies and recombinant
      interleukin-4 (IL-4) triggers a cascade of signal transduction network events
      that lead to switching the immunoglobulin isotopes from IgM to IgE. This chapter
      describes the methodology of class switch recombination assay for assessment of
      the effect of the environmental pollutants in toxicological laboratory
      diagnostics.

PMID- 24908304
TI  - A mix-and-measure assay for determining the activation status of endogenous Cdc42
      in cytokine-stimulated macrophage cell lysates.
AB  - Cytokine stimulations of leukocytes many times result in transient activation of
      the p21 Rho family of small GTPases. The role of these molecules during cell
      migration and chemotaxis is well established. The traditional approach to study
      the activation dynamics of these proteins involves affinity pull-downs that are
      often cumbersome and prone to errors. Here, we describe a reagent and a method of
      simple "mix-and-measure" approach useful for determining the activation status of
      endogenous Cdc42 GTPase from cell lysates.

PMID- 24908305
TI  - Analysis of the cell surface expression of cytokine receptors using the surface
      protein biotinylation method.
AB  - Cytokines are pleiotropic, low-molecular-weight proteins that regulate the immune
      responses to infection and inflammation. They stimulate the immune responses by
      binding to cytokine receptors on the cell plasma membrane. Thus, knowledge of the
      expression level of particular cytokine receptors on cell surface is crucial for
      understanding the cytokine function and regulation. One of the techniques to
      explore the membrane embedded cytokine receptors is cell surface biotinylation.
      Biotinylated surface proteins can be rapidly purified through the strong
      interaction between biotin and streptavidin. Here, we describe the procedure for
      surface biotinylation and purification of biotinylated cytokine receptors for
      further downstream analysis. 

PMID- 24908306
TI  - Detection of CXCR2 cytokine receptor surface expression using immunofluorescence.
AB  - The interleukin-8 (IL-8, CXCL8) chemokine, also known as the neutrophil
      chemotactic factor, is a cytokine that plays a key role in inflammatory response,
      cell proliferation, migration, and survival. IL-8 expression is increased not
      only in inflammatory disorders, but also in many types of cancer, including
      prostate cancer. IL-8 acts as a ligand for the C-X-C chemokine receptor 2 (CXCR2)
      protein present on the cell plasma membrane. Binding of the IL-8 ligand to the
      CXCR2 receptor results in an intracellular signaling pathway mediated by GTP
      binding proteins coupled to the receptor itself. Knowledge of the CXCR2
      expression levels facilitates the understanding of the role and function of IL-8.
      In this chapter, we describe a protocol that uses the immunofluorescence method
      and confocal microscopy to analyze the CXCR2 surface expression in human prostate
      cancer cells. However, this protocol is easily adaptable to analyze the surface
      expression of other cytokine receptors in different cell types.

PMID- 24908307
TI  - Detecting Tie2, an endothelial growth factor receptor, by using
      immunohistochemistry in mouse lungs.
AB  - Immunohistochemical (IHC) staining is an invaluable, sensitive, and effective
      method to detect the presence and localization of proteins in the cellular
      compartment in tissues. The basic concept of IHC is detecting the antigen in
      tissues by means of specific antibody binding, which is then demonstrated with a
      colored histochemical reaction that can be observed under a light microscope. The
      most challenging aspect of IHC techniques is optimizing the precise experimental
      conditions that are required to get a specific and a strong signal. The critical
      steps of IHC are specimen acquisition, fixation, permeabilization, detection
      system, and selection of the antigen specific antibody and its optimization.
      Here, we elaborate the technique using the endothelial growth factor binding
      receptor Tie2 in mouse lungs. 

PMID- 24908308
TI  - Use of shRNA for stable suppression of chemokine receptor expression and function
      in human cancer cell lines.
AB  - In this chapter, we describe a protocol used for stable silencing of chemokine
      receptor CXCR7 in human cancer cells using shRNA in a lipid transfection setting,
      previously published by our laboratory. We provide thorough detail and background
      information about the process of shRNA to clarify the importance of this process.
      We use CXCR7 shRNA and scrambled sequence shRNA constructs cloned into a pRS
      plasmid under the control of a U6 promoter for stable expression. Human cancer
      cells are transfected with shRNA-pRS using Lipofectamine 2000. Cells stably
      expressing the shRNA are selected from transfected cultures following 2 weeks in
      medium containing the selection antibiotic puromycin. The emergent cell colonies
      are evaluated for knockdown of CXCR7 mRNA and protein expression by q-PCR and
      immunoblotting with rabbit anti-CXCR7 IgG, respectively.

PMID- 24908309
TI  - Intracellular staining and detection of cytokines by fluorescence-activated flow
      cytometry.
AB  - The detection of cytokines inside cells producing them has made a tremendous
      impact on the way immune reactivity is measured. Intracellular cytokine staining
      is the only immunological technique allowing determination of antigen-specific T
      cell function and phenotype at the same time; for this reason, it is one of the
      most popular methods to measure antigenicity in the evaluation of vaccine
      efficacy and in the study of infectious diseases. It is a flow cytometric
      technique based on staining of intracellular cytokines and cell markers (surface
      or cytoplasmic) with fluorescent antibodies after short term culture of
      stimulated immune cells in the presence of a protein secretion inhibitor,
      followed by fixation and permeabilization. Most experiments involve detection of
      five to ten different colors but many more can be detected by modern flow
      cytometers. Here, we discuss our experience using a standard protocol for
      intracellular cytokine staining. 

PMID- 24908310
TI  - Cytokine detection by flow cytometry.
AB  - Analysis of intracellular cytokines is extremely important in the clinical
      treatment of numerous diseases. Flow cytometry (FCM) is a highly effective
      technique that detects intracellular cytokines using specific fluorescence
      labeled antibodies. The common steps of this assay include cell collection,
      fixation, permeabilization, blocking, intracellular staining and analysis by FCM.
      This technique also allows for analyzing the biological function of cytokines. In
      this chapter, we describe a modified method to detect the specific intracellular
      cytokine staining using FCM, with an emphasis on the effects of variables
      including samples, temperature, buffers, data acquisition, and analysis. 

PMID- 24908311
TI  - Analysis of IL-17 production by flow cytometry and ELISPOT assays.
AB  - Interleukin (IL)-17 represents a family of cytokines with six members, namely IL
      17A, B, C, D, E, and F. IL-17A and IL-17F are best studied proinflammatory
      cytokines. CD4(+) T helper cells producing IL-17A have been identified as a
      distinct T helper subset, Th17 cells. IL-17 and Th17 cells are important
      mediators in tissue inflammation in immune-mediated inflammatory diseases. IL-17
      is also produced by other immune cells and plays an important role in host
      defense against microbial infection. Cell-based assays are sensitive and
      quantitative, and enable identification of cellular sources of IL-17 production.
      This chapter describes usage of flow cytometry and ELISPOT assays to quantify IL
      17A-producing cells in disease and in vitro experiments to study T cell function.

PMID- 24908312
TI  - Interleukin-1 (IL-1) immunohistochemistry assay in oral squamous cell carcinoma.
AB  - This chapter describes an immunohistochemistry method to analyze interleukin-1
      (IL-1) in oral squamous cell carcinoma. The described protocol has been optimized
      for IL-1 detection in formalin-fixed paraffin-embedded oral tissue sections by
      light microscopy. A few common pitfalls and problems associated with
      immunohistochemical staining are discussed. 

PMID- 24908313
TI  - Immunofluorescence and subsequent confocal microscopy of intracellular TNF in
      human neutrophils.
AB  - Immunofluorescence is an important technique required to observe expression,
      localization and colocalization of proteins within the cell. Here we describe the
      immunofluorescence and subsequent confocal microscopy technique of tumor necrosis
      factor-alpha (TNF) in human neutrophils (polymorphonuclear leukocytes; PMN). The
      qualitative technique can be used to observe the expression pattern changes from
      resting to stimulated leukocytes. Colocalization with other cytokines, proteins,
      or organelles can be observed. This immunofluorescence technique can be done in 1
      2 days. 

PMID- 24908314
TI  - Evaluating cytoplasmic and nuclear levels of inflammatory cytokines in cancer
      cells by western blotting.
AB  - Increased expression and cellular release of inflammatory cytokines, interleukin
      8 (IL-8; CXCL8), and high mobility group box-1 (HMGB1) are associated with
      increased cell proliferation, angiogenesis, and metastasis during cancer
      progression. In prostate and ovarian cancer cells, increased levels of IL-8 and
      HMGB1 correlate with poor prognosis. We have recently shown that proteasome
      inhibition by bortezomib (BZ) specifically increases IL-8 release from metastatic
      prostate and ovarian cancer cells. In this chapter, we describe a protocol to
      analyze the cytoplasmic and nuclear levels of IL-8 and HMGB1 in prostate and
      ovarian cancer cells by western blotting. IL-8 is localized in the cytoplasm in
      both cell types, and its protein levels are significantly increased by BZ. In
      contrast, HMGB1 is localized in the nucleus, and BZ increases its nuclear levels
      only in ovarian cancer cells. The protocol includes isolation of cytoplasmic and
      nuclear extracts, followed by SDS electrophoresis and western blotting, and can
      be easily modified to analyze the cytoplasmic and nuclear cytokine levels in
      other cell types.

PMID- 24908315
TI  - Western analysis of intracellular interleukin-8 in human mononuclear leukocytes.
AB  - Most cytokines are stored in the cytoplasm until their release into the
      extracellular environment; however, some cytokines have been reported to localize
      in the nucleus. Traditional whole cell extract preparation does not provide
      information about the intracellular localization of cytokines. Here, we describe
      how to prepare cytoplasmic and nuclear extracts that can be analyzed by
      immunoblotting. While in this chapter we use this method to analyze intracellular
      localization of interleukin-8 (IL-8) in human mononuclear leukocytes, this
      protocol is adaptable to any cell type or protein of interest. 

PMID- 24908316
TI  - Quantitative analysis of bortezomib-induced IL-8 gene expression in ovarian
      cancer cells.
AB  - Interleukin-8 (IL-8), originally discovered as the neutrophil chemoattractant and
      inducer of leukocyte-mediated inflammation, contributes to cancer progression
      through its induction of tumor cell proliferation, survival, and migration. IL-8
      expression is increased in many types of advanced cancers, including ovarian
      cancer, and correlates with poor prognosis. Bortezomib (BZ) is the first FDA
      approved proteasome inhibitor that has shown remarkable antitumor activity in
      multiple myeloma and other hematological malignancies. In solid tumors, including
      ovarian carcinoma, BZ has been less effective as a single agent; however, the
      mechanisms remain unknown. We have recently shown that in ovarian cancer cells,
      BZ greatly increases IL-8 expression, while expression of other NFkappaB
      regulated cytokines, IL-6 and TNF, is unchanged. In this chapter, we describe a
      protocol that uses real-time qRT-PCR to quantitatively analyze mRNA levels of IL
      8 and IL-6 in BZ-treated ovarian cancer cells. The protocol can be easily
      modified and used for analysis of other cytokines in different cell types.

PMID- 24908317
TI  - Analysis of LPS-induced, NFkappaB-dependent interleukin-8 transcription in kidney
      embryonic cell line expressing TLR4 using luciferase assay.
AB  - Gene expression is orchestrated by a complex network of signal transduction
      pathways that typically originate on cell surface receptors and culminate in DNA
      binding transcription factors, which translocate to the nucleus and bind cis
      regulatory elements in promoter regions of genes, thereby inducing de novo
      synthesis of the nascent RNA transcripts and their splicing. Gene expression
      arrays monitor abundance of the matured, spliced cDNA, which undergoes additional
      posttranscriptional modifications that greatly affect the half-life of the cDNA.
      Thus, the relative abundance of cDNA is not necessarily commensurable with the
      activity of promoters of the corresponding genes. In contrast, reporter gene
      assays provide valuable insight into the regulation of gene expression at the
      level of transcription and allow for discerning the contribution of individual
      transcription factors into changes in gene expression. Here, we describe a robust
      reporter gene assay method that is useful for exploration of transcription
      regulatory network, which regulates gene expression in response to inflammation.
      The method is exemplified by using the promoter region of the prototypic pro
      inflammatory chemokine interleukin-8 (IL-8, CXCL8), which plays an important role
      in immune response as well as carcinogenesis. Using the luciferase reporter gene
      assay, we analyze the activation status of the IL-8 promoter in
      lipopolysaccharide (LPS)-stimulated human embryonic kidney cells. 

PMID- 24908318
TI  - Chromatin immunoprecipitation analysis of bortezomib-mediated inhibition of
      NFkappaB recruitment to IL-1beta and TNFalpha gene promoters in human
      macrophages.
AB  - Interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNF) are important pro
      inflammatory cytokines involved in the mediation of the immune response,
      inflammation, tissue repair, and tumor progression. Regulation of IL-1 and TNF
      expression is mediated at the level of transcription by the transcription factor
      NFkappaB. Inhibition of NFkappaB activity by the proteasome inhibitor bortezomib
      (BZ) has been used as a frontline therapy in multiple myeloma and other
      hematological malignancies. In this chapter, we describe a protocol that uses
      chromatin immunoprecipitation (ChIP) to analyze the NFkappaB recruitment to
      endogenous IL-1 and TNF promoters in BZ-treated human macrophages. Corresponding
      to the BZ-suppressed mRNA levels of IL-1 and TNF, we show that BZ inhibits p65
      NFkappaB recruitment to IL-1 and TNF promoters. This study specifically uses U937
      macrophages, but the protocol could be easily modified to analyze the regulation
      of NFkappaB recruitment in other cell types.

PMID- 24908319
TI  - Analysis of TGFbeta1 and IL-10 transcriptional regulation in CTCL cells by
      chromatin immunoprecipitation.
AB  - The immunosuppressive cytokines transforming growth factor beta1 (TGFbeta1) and
      interleukin-10 (IL-10) regulate a variety of biological processes including
      differentiation, proliferation, tissue repair, tumorigenesis, inflammation, and
      host defense. Aberrant expression of TGFbeta1 and IL-10 has been associated with
      many types of autoimmune and inflammatory disorders, as well as with many types
      of cancer and leukemia. Patients with cutaneous T cell lymphoma (CTCL) have high
      levels of malignant CD4+ T cells expressing IL-10 and TGFbeta1 that suppress the
      immune system and diminish the antitumor responses. The transcriptional
      regulation of TGFbeta1 and IL-10 expression is orchestrated by several
      transcription factors, including NFkappaB. However, while the transcriptional
      regulation of pro-inflammatory and anti-apoptotic genes by NFkappaB has been
      studied extensively, much less is known about the NFkappaB regulation of
      immunosuppressive genes. In this chapter, we describe a protocol that uses
      chromatin immunoprecipitation (ChIP) to analyze the transcriptional regulation of
      TGFbeta1 and IL-10 by measuring recruitment of NFkappaB p65, p50, c-Rel, Rel-B,
      and p52 subunits to TGFbeta1 and IL-10 promoters in human CTCL Hut-78 cells.

PMID- 24908320
TI  - Radiolabeled semi-quantitative RT-PCR assay for the analysis of alternative
      splicing of interleukin genes.
AB  - Alternative splicing evolved as a very efficient way to generate proteome
      diversity from a limited number of genes, while at the same time modulating
      posttranscriptional events of gene expression-such as stability, turnover,
      subcellular localization, binding properties, and general activity of both mRNAs
      and proteins. Since the vast majority of human genes undergo alternative
      splicing, it comes to no surprise that interleukin genes also show extensive
      alternative splicing. In fact, there is a growing body of evidence indicating
      that alternative splicing plays a central role in modulating the pleiotropic
      functions of cytokines, and aberrant expression of alternatively spliced
      interleukin mRNAs has been linked to disease. However, while several interleukin
      splice variants have been described, their function is still poorly understood.
      This is particularly relevant, since alternatively spliced cytokine isoforms can
      act both as disease biomarkers and as candidate entry points for therapeutic
      intervention. In this chapter we describe a protocol that uses radiolabeled semi
      quantitative RT-PCR to efficiently detect, analyze, and quantify alternative
      splicing patterns of cytokine genes. 

PMID- 24908321
TI  - Eculizumab in dense-deposit disease after renal transplantation.
AB  - BACKGROUND: Dense-deposit disease (DDD) is a rare glomerulopathy characterized by
      electron-dense deposits in the glomerular basement membrane. About 50 % of
      patients with DDD progress to end-stage kidney disease and require dialysis
      within 10 years of diagnosis, and the disease often recurs after renal
      transplantation. CASE-DIAGNOSIS/TREATMENT: We describe a 14-year-old girl with
      recurrent DDD in her transplanted kidney. Clinical onset was at 8 years of age,
      when steroid-resistant nephrotic syndrome was diagnosed with microhematuria,
      severe hypocomplementemia and normal kidney function. Although remission was
      initially observed after several plasma exchanges, nephrotic proteinuria returned
      and kidney function further declined 1 year later. The patient received a living
      related kidney transplant. Initial allograft function was good, but proteinuria
      reappeared 3 months after transplantation, accompanied by a slight deterioration
      in kidney function. After histological confirmation of DDD recurrence and
      subsequent management with plasmapheresis, the patient was treated for 30 months
      with eculizumab, a humanized monoclonal antibody that binds to C5 complement
      protein. This intervention proved effective and resulted in complement
      inhibition, sustained remission of proteinuria and preservation of renal
      function. A graft biopsy 6 months later showed no progression of the renal
      lesions. CONCLUSIONS: Early clinical and histological recurrence of DDD in the
      transplanted kidney in this 14-year-old patient was treated for 30 months with
      eculizumab. The patient remains asymptomatic, has no proteinuria and her kidney
      function is intact.

PMID- 24908322
TI  - Fludrocortisone as a new tool for managing tubulopathy after pediatric renal
      transplantation: a series of cases.
AB  - BACKGROUND: The management of tubulopathies after renal transplantation (RTx) may
      require high doses of sodium and bicarbonate, reducing the quality of life and
      therapeutic compliance of the patient. Some studies on adult patients have
      highlighted the benefits of fludrocortisone (fludro) in the treatment of severe
      tubulopathies. METHODS: This study was a retrospective review of the medical
      charts of 15 children, aged 12.4 (range 3.6-17.4) years who received fludro after
      RTx. RESULTS: With the administration of fludro, both sodium bicarbonate and
      chloride supplementation decreased, from 10 (range 0-14) to 0 (0-5) g/day, and
      from 9 (0-20) to 0 (0-3) g/day, respectively (both p < 0.001). Serum potassium
      also significantly decreased (4.6 +/- 0.4 vs. 3.3 +/- 0.6 mmol/L; p < 0.001), but
      there was no significant effect on renal function. Both systolic and diastolic
      blood pressure increased significantly. Fludro therapy was stopped in six
      patients due to side-effects (arterial hypertension, hypokalemia during acute
      diarrhea, gastric pain, n = 3), parental decision (n = 1), inefficacy and/or non
      compliance (n = 1) and scheduled withdrawal (n = 1). Four of these patient had
      subsequent increasing requirements for bicarbonate and/or sodium supplementation,
      which ultimately required the re-introduction of fludro in two of these patients.
      CONCLUSIONS: Based on our findings, fludro would appear to be an effective
      therapy in most cases of severe tubulopathy after RTx. Further prospective
      studies are required to validate this indication and to determine the optimal
      dose and timing of treatment to avoid side-effects as well as the clinical and
      biological follow-up.

PMID- 24908323
TI  - Ambulatory blood pressure monitoring is recommended in the clinical management of
      children with a solitary functioning kidney.
AB  - BACKGROUND: Children with a solitary functioning kidney are at increased risk of
      developing chronic kidney disease. Hypertension may be an early indicator of
      renal dysfunction in these patients. We determined blood pressure (BP) profiles
      of children with a solitary functioning kidney by using ambulatory BP monitoring
      (ABPM). METHODS: To assess the occurrence with (pre)hypertension, we compared
      ABPM to office BP measurement in 47 children with a solitary functioning kidney.
      None of the subjects used antihypertensive agents or had been hypertensive during
      previous clinical visits. RESULTS: Mean age of study subjects was 12.7 (+/-3.3)
      years. Hypertension was identified in ten (21 %) subjects with ABPM, whereas only
      two (4 %) children were hypertensive during office BP measurement (p < 0.01).
      Fifteen (32 %) children had an ABPM standard deviation (SD) value >=90th
      percentile versus six (13 %) subjects based on office BP measurement (p = 0.051).
      Although 24-h ABPM SD scores were higher in the congenital type than in the
      acquired type of solitary functioning kidney (p <= 0.01), the proportions of
      subjects with 24-h ABPM hypertension were similar between groups (congenital 25 %
      versus acquired 16 %; p = NS). CONCLUSIONS: Based on ABPM, one in five children
      with a solitary functioning kidney has hypertension. As the majority of these
      subjects were not hypertensive during office BP measurements, ABPM should be
      considered in the clinical management of solitary functioning kidney patients.

PMID- 24908324
TI  - Gaining the Patient Reported Outcomes Measurement Information System (PROMIS)
      perspective in chronic kidney disease: a Midwest Pediatric Nephrology Consortium
      study.
AB  - BACKGROUND AND OBJECTIVES: Chronic kidney disease is a persistent chronic health
      condition commonly seen in pediatric nephrology programs. Our study aims to
      evaluate the sensitivity of the Patient Reported Outcomes Measurement Information
      System (PROMIS) pediatric instrument to indicators of disease severity and
      activity in pediatric chronic kidney disease. METHODS: This cross sectional study
      included 233 children 8-17 years old, with chronic kidney disease from 16
      participating institutions in North America. Disease activity indicators,
      including hospitalization in the previous 6 months, edema, and number of
      medications consumed daily, as well as disease severity indicators of kidney
      function and coexisting medical conditions were captured. PROMIS domains,
      including depression, anxiety, social-peer relationships, pain interference,
      fatigue, mobility, and upper extremity function, were administered via web-based
      questionnaires. Absolute effect sizes (AES) were generated to demonstrate the
      impact of disease on domain scores. Four children were excluded because of
      missing glomerular filtration rate (GFR) estimations. RESULTS: Of the 229
      children included in the final analysis, 221 completed the entire PROMIS
      questionnaire. Unadjusted PROMIS domains were responsive to chronic kidney
      disease activity indicators and number of coexisting conditions. PROMIS domain
      scores were worse in the presence of recent hospitalizations (depression AES
      0.33, anxiety AES 0.42, pain interference AES 0.46, fatigue AES 0.50, mobility
      AES 0.49), edema (depression AES 0.50, anxiety AES 0.60, pain interference AES
      0.77, mobility AES 0.54) and coexisting medical conditions (social peer
      relationships AES 0.66, fatigue AES 0.83, mobility AES 0.60, upper extremity
      function AES 0.48). CONCLUSIONS: The PROMIS pediatric domains of depression,
      anxiety, social-peer relationships, pain interference, and mobility were
      sensitive to the clinical status of children with chronic kidney disease in this
      multi-center cross sectional study. We demonstrated that a number of important
      clinical characteristics including recent history of hospitalization and edema,
      affected patient perceptions of depression, anxiety, pain interference, fatigue
      and mobility. The PROMIS instruments provide a potentially valuable tool to study
      the impact of chronic kidney disease. Additional studies will be required to
      assess responsiveness in PROMIS score with changes in disease status over time.

PMID- 24908325
TI  - Polycyclic aromatic hydrocarbons in the soils of a densely populated region and
      associated human health risks: the Campania Plain (Southern Italy) case study.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a major class of environmental
      pollutants mainly arising from anthropogenic activities. In this paper, the
      behavior and the distribution patterns of sixteen PAHs, listed as priority
      pollutants by the United States Environmental Protection Agency, were evaluated
      in 119 soil samples collected in different areas of Campania region in the
      southern Italy. The observation of the geochemical distribution patterns showed
      that both high and low molecular weight PAHs are mostly concentrated within the
      metropolitan area of Naples, the Agro Aversano area, and, partly, the Sarno River
      basin. In accordance with the Italian environmental law (D. Lgs. 152/2006), these
      areas should be considered potentially contaminated and not suitable for a
      residential use unless an environmental risk analysis does not demonstrate their
      safety. As a consequence, a preliminary quantitative risk assessment enhanced by
      the use of GIS was run revealing the existence of an incremental lifetime cancer
      risk higher than 1 * 10(-5) for the city of Naples and for some other populous
      areas.

PMID- 24908327
TI  - Different efficacy of EGFR tyrosine kinase inhibitors and prognosis in patients
      with subtypes of EGFR-mutated advanced non-small cell lung cancer: a meta
      analysis.
AB  - BACKGROUND: Nearly 85 % of lung-cancer-specific epidermal growth factor receptor
      (EGFR) sensitive mutations comprise a substitution at position 858 (21L858R) and
      deletion mutants in exon 19 (19del). The aim of this study was to assess the role
      of EGFR mutation subtypes in predicting the efficacy of EGFR tyrosine kinase
      inhibitors (EGFR TKIs) and the prognosis of patients with advanced non-small cell
      lung cancer (NSCLC). METHOD: We systematically searched for eligible articles
      investigating the association between EGFR mutation subtypes and the efficacy of
      EGFR TKIs and the prognosis of patients with NSCLC. The summary risk ratio (RR)
      and mean difference (MD) were calculated using meta-analysis. In addition, we
      used variance analysis for the progression-free survival data (PFS) and used the
      rank sum test for the overall survival data. RESULTS: We identified 22 eligible
      trials involving 1,082 patients. The objective response rate of the 19del
      mutation group was significantly higher than the 21L858R mutation group (RR 1.23;
      95 % CI 1.12-1.36; P < 0.0001). The PFS (MD 3.55; 95 % CI 0.90-6.20; P = 0.009;
      MD 2.57; 95 % CI 0.51-4.62; P = 0.01) and overall survival (OS) (MD 10.52; 95 %
      CI 5.10-15.93; P = 0.0001) of the 19del mutation group were significantly longer
      than the 21L858R mutation group; the same results were observed in the variance
      analysis and rank sum test. CONCLUSION: The 19del mutation may be a more
      efficient clinical marker for predicting the response of patients with NSCLC to
      EGFR TKIs. Furthermore, patients with the 19del mutation have both a longer PFS
      and OS. The 19del mutation is also the prognostic factor for patients with NSCLC.

PMID- 24908328
TI  - Filamin A expression correlates with proliferation and invasive properties of
      human metastatic melanoma tumors: implications for survival in patients.
AB  - PURPOSE: Filamin A (FLNa) cross-links actin filaments into dynamic orthogonal
      networks and interacts with binding proteins of diverse cellular functions that
      are implicated in cell growth and motility regulation. Here, we tested the
      hypothesis that FLNa plays a role in cancer proliferation and metastasis via the
      regulation of epidermal growth factor receptor (EGFR) function. METHODS: Ectopic
      expression and knockdown of FLNa in human melanoma cell lines was performed to
      investigate changes in cellular proliferation, migration and invasion in vitro
      and tumor growth in a xenograft model in the mouse. The role of FLNa in EGFR
      expression and signaling was evaluated by Western blot. Immunohistochemistry was
      performed on histological sections of human melanoma tumors to determine whether
      an association existed between FLNa and overall survival. RESULTS: The depletion
      of FLNa significantly reduced the proliferation, migration and invasion of two
      melanoma cell lines in vitro and was associated with smaller tumors in a
      xenograft model in vivo. EGF-induced phosphorylation of EGFR and activation of
      the Raf-MEK-ERK cascade was negatively affected by the silencing of FLNa both in
      vitro and in vivo. Cancer patients with low melanoma tumor FLNa expression have
      improved survival benefit. CONCLUSION: These data indicate that enhanced
      tumorigenesis occurs through increase in EGF-induced EGFR activation in FLNa
      expressing melanoma cells and that high FLNa levels are predictors of negative
      outcome for patients with melanoma tumors.

PMID- 24908329
TI  - Estrogen receptor promoter methylation predicts survival in low-grade ovarian
      carcinoma patients.
AB  - PURPOSE: Ovarian carcinoma is the third most common gynecological cancer and only
      short recurrence-free survival and overall survival times are achieved. The role
      of the estrogen receptor expression is well studied in breast cancer and breast
      cancer cell lines. Patients with positive estrogen receptor expression have a
      lower risk for recurrence and a better overall survival. Previous studies have
      shown that ESR1 methylation influences ovarian cancer development and might thus
      play a role regarding prognosis of ovarian carcinoma. METHODS: A total of 75
      patients were identified that were treated for ovarian carcinoma by debulking
      surgery and adjuvant standard chemotherapy. Isolation and bisulfite treatment of
      genomic DNA from serial sections of surgically resected ovarian carcinoma tissue
      was performed using commercially available kits. For the detection of methylated
      ESR1 promoter sequences, real-time methylation-specific PCR was used. RESULTS:
      Promoter methylation did not show a correlation between clinical-pathological
      data for all patients. However, within the subgroup of low-grade ovarian
      carcinoma patients and patients with an ovarian tumor of low malignant potential
      methylation of the ESR1 promoter inversely correlated with survival (p = 0.031).
      CONCLUSIONS: Although small numbers of ovarian carcinoma patients were analyzed,
      methylation status might be useful as a prognostic marker within the subgroup of
      low-grade ovarian carcinoma patients. Further studies should investigate a larger
      cohort and also address the use of demethylation agents with respect to improve
      patient's prognosis in this subgroup of ovarian carcinoma patients.

PMID- 24908330
TI  - A novel scoring system to predict the incidence of invasive fungal disease in
      salvage chemotherapies for malignant lymphoma.
AB  - The requirement of antifungal prophylaxis has not been established in the
      chemotherapies for malignant lymphoma. This study was conducted to explore the
      incidence of invasive fungal diseases (IFD) and their risk factors in patients
      receiving salvage therapies for malignant lymphoma. We retrospectively analyzed
      177 consecutive patients who received these therapies (705 courses in total) at
      our institute. IFD were observed in 16 courses and the incidence was 2.3 %. A
      multivariate analysis showed that the factors associated with IFD were primary
      refractoriness (adjusted odds ratio (aOR), 4.22; 95 % confidence interval (CI),
      1.38-13.0; p value = 0.012), two (aOR, 10.5, 95 % CI, 1.20-91.7; p = 0.033) or
      more (aOR, 26.2; 95 % CI, 3.27-210; p = 0.002) previous treatment lines, and the
      minimum neutrophil count during the therapies equal to or less than 500/MUL (aOR,
      9.69; 95 % CI, 1.25-74.9; p = 0.030). Using these factors, we created the IFD
      scoring model by assigning one point to each of primary refractoriness, two
      previous treatment lines and treatment that caused neutropenia (<=500/MUL minimal
      neutrophil count) and two points to three or more previous treatment lines. The
      IFD incidence of lower risk group (IFD score <3) was 0.19 % and that of higher
      (IFD score >=3) was 9.0 %. In conclusion, adequate prophylaxis for IFD might be
      required for patients with primary refractoriness, repeated therapies, or
      therapies which cause neutropenia. Furthermore, the IFD scoring model of this
      study underscores the need to account for disease and host factors in determining
      administration of adequate prophylaxis in salvage treatments for malignant
      lymphoma.

PMID- 24908331
TI  - Long-term outcome of patients with advanced-stage cutaneous T cell lymphoma
      treated with gemcitabine.
AB  - The choice of treatment for cutaneous T cell lymphoma (CTCL) is often determined
      by institutional experience, particularly as there is a paucity of data from
      phase III trials and a lack of consensus concerning treatment of the advanced
      stages. Among the several second-line and experimental drugs, gemcitabine could
      be considered one of the most suitable options for pretreated CTCL. Since it is
      difficult to find in literature the long-term outcome regarding the efficacy of a
      single-agent drug in pretreated patients and, in particular, in rare diseases
      such as CTCL, a retrospective observational study was conducted with the aim of
      evaluating the long-term outcome of CTCL patients treated with gemcitabine.
      Twenty-five patients with at least one therapy (range 1-8) performed prior to
      gemcitabine were found. After gemcitabine treatment, the overall response was 48
      % with a 20 % of complete responses. At 15 years, the estimated overall survival
      is 47 %, progression-free survival 8.8 %, and disease-free survival 40 % (median
      reached at 2.9 years). All patients received at least three cycles and no grade 3
      4 hematological adverse events occurred. At the latest follow-up, two patients
      are still in continuous complete response. This long-term update on the role of
      gemcitabine as a single agent in pretreated advanced-stage CTCL confirms this
      monotherapy as effective and safe.

PMID- 24908333
TI  - Interim results in clinical trials: do we need to keep all interim randomised
      clinical trial results confidential?
AB  - OBJECTIVES: Guidelines for the conduct of clinical trials emphasize the
      importance of keeping the interim results from the main endpoints confidential,
      in order to maintain the integrity of the trial and to safeguard patients'
      interests. However, is this essential in every situation? MATERIALS AND METHODS:
      We review the evidence for these guidelines and consider recent randomised trials
      that have released interim results, to assess their impact on the success of the
      trial. However, because the strength of opinion to keep interim results
      confidential is so strong, there are limited examples of such trials. RESULTS: In
      the QUARTZ trial (which is assessing the value of whole brain radiotherapy in
      patients with brain metastases from non-small cell lung cancer) the decision to
      release interim results was taken in response to threatened closure due to poor
      accrual, whereas in the GRIT trial (which compared two obstetric strategies for
      the delivery of growth retarded pre-term fetuses) the regular release of interim
      results was pre-planned. Nevertheless there are a number of common factors
      between these two trials. In particular, the trial treatments were already in
      wide use, with no reliable randomised evidence on which treatment should be used
      for which patients, and there was diverse clinical opinion, which meant that
      accrual was likely to be challenging. In a situation where a quarter to a third
      of trials do not accrue their required number of patients, the QUARTZ trial
      continues to accrue patients, and the GRIT trial successfully accrued its target
      of nearly 600 babies. CONCLUSIONS: This article therefore argues that there is a
      need to re-consider whether it is always essential to keep the interim results of
      randomized clinical trials confidential, and suggests some criteria that may help
      groups planning or running challenging trials decide whether releasing interim
      results would be a useful strategy.

PMID- 24908332
TI  - Thymic epithelial tumors express vascular endothelial growth factors and their
      receptors as potential targets of antiangiogenic therapy: a tissue micro array
      based multicenter study.
AB  - OBJECTIVES: Tumor angiogenesis is an essential and complex process necessary for
      the growth of all tumors which represents a potential therapeutic target.
      Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or
      their receptor tyrosine kinases have been approved by the FDA. In thymic
      epithelial tumors (TET), targeted therapies have been sporadically applied due to
      their rarity. To ascertain the presence of potential therapeutic targets, we
      analyzed by immunohistochemistry the expression of angiogenesis-related
      biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA).
      MATERIALS AND METHODS: We assessed by immunohistochemistry the expression of the
      possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD,
      VEGFR1, VEGFR2, VEGFR3, and PDGFRbeta, in a TMA series of 200 TET collected in
      the framework of a multi-institutional collaborative project for Rare Diseases.
      RESULTS: When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas)
      contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD
      (P<0.001, P<0.001, and P<0.001) growth factors, and their receptors VEGFR1
      (P=0.002), VEGFR2 (P=0.013), and VEGFR3 (P=0.041). No differences were observed
      in terms of PDGFRbeta expression. CONCLUSIONS: According to our data, it is
      possible to hypothesize the existence of multiple paracrine and/or autocrine
      loops in TET, particularly in the high-risk ones, involved in TET growth and
      progression. Anti-angiogenic agents, directed to inhibit these loops, are
      therefore to be considered as potential tools in advanced TET therapy.

PMID- 24908334
TI  - CdS nanoclusters doped with divalent atoms.
AB  - ZnS and CdS small nanoclusters have been predicted to trap alkali metals and
      halogen atoms. However would this kind of nanocompounds be able to encapsulate
      dianions and dications? This would be very interesting from an experimental point
      of view, since it would allow the isolation of such divalent ions. Moreover, the
      resulting endohedral complexes would serve as building blocks for new cluster
      assembled materials, with enhanced stability arising from the electrostatic
      interaction between the incarcerated ions. In this work we have studied the
      structure and stability of (X@(CdS)i)(+/-2) with X = Be, Mg, Ca, O, S, Se and i =
      9, 12, 15, 16 on the basis of Density Functional Theory and Quantum Molecular
      Dynamics simulations. Most of the nanoclusters are found to trap both chalcogen
      and alkaline earth atoms. Furthermore, the chalcogen doped clusters are
      calculated to be both thermodynamically and thermally stable. However, only a few
      of alkaline earth metal doped structures are predicted to be thermally stable.
      Therefore, the charge of the dopant atom appears to be crucial in the endohedral
      doping. Additionally, the absorption spectra of the title compounds have been
      simulated by means of Time Dependent Density Functional Theory (TDDFT)
      calculations. The calculated optical features show a blueshift with respect to
      the bulk CdS wurtzite. Furthermore, doping modifies notably the optical spectra
      of nanoclusters, as the absorption spectra shift to lower energies upon
      encapsulation.

PMID- 24908335
TI  - Occurrence and in-stream attenuation of wastewater-derived pharmaceuticals in
      Iberian rivers.
AB  - A multitude of pharmaceuticals enter surface waters via discharges of wastewater
      treatment plants (WWTPs), and many raise environmental and health concerns.
      Chemical fate models predict their concentrations using estimates of mass
      loading, dilution and in-stream attenuation. However, current comprehension of
      the attenuation rates remains a limiting factor for predictive models. We
      assessed in-stream attenuation of 75 pharmaceuticals in 4 river segments, aiming
      to characterize in-stream attenuation variability among different pharmaceutical
      compounds, as well as among river segments differing in environmental conditions.
      Our study revealed that in-stream attenuation was highly variable among
      pharmaceuticals and river segments and that none of the considered pharmaceutical
      physicochemical and molecular properties proved to be relevant in determining the
      mean attenuation rates. Instead, the octanol-water partition coefficient (Kow)
      influenced the variability of rates among river segments, likely due to its
      effect on sorption to sediments and suspended particles, and therefore
      influencing the balance between the different attenuation mechanisms
      (biotransformation, photolysis, sorption, and volatilization). The magnitude of
      the measured attenuation rates urges scientists to consider them as important as
      dilution when aiming to predict concentrations in freshwater ecosystems. 

PMID- 24908336
TI  - Calves' sex ratio in naturally and artificially bred cattle in central Ethiopia.
AB  - A study was undertaken with the objective to identify some intrinsic (genotype of
      the cow, estrus time and parity) and extrinsic factors (service type, service
      time and estrus seasons) that affect calf sex ratio in naturally and artificially
      bred cattle in the central highlands of Ethiopia. A total of 4657 calving events
      were extracted from the long-term dairy cattle genetic improvement experiment at
      Holetta Agricultural Research Center. Factors that affect the logit of the
      probability of a female calf being born were obtained by using PROC GENMODE in
      Statistical Analysis System. Moreover, multivariate analysis was performed using
      PROC LOGISTIC procedure using forward selection procedure. Accordingly, genotype
      of the cow, parity, estrus season, and service type had considerable influences
      on calf sex ratio. However, estrus time and service time did not affect calf sex
      ratio (chi(2) = 0.83 and 0.79, respectively). In Ethiopia, smallholder dairy
      farmers often complain that artificial insemination (AI) skewed to producing more
      male calves. However, our study showed that AI did not alter female-to-male calf
      sex ratio. On the contrary, natural mating increases the probability of female
      calves born (odds ratio 1.38) over AI. Heifer/cows that showed estrus and bred
      during the harsh seasons of the years produced more female calves than those that
      bred during the good seasons of the year. This strongly agreed with Trivers and
      Willard sex allocation theory.

PMID- 24908337
TI  - Prostaglandin E1 or E2 inhibits an oxytocin-induced premature luteolysis in ewes
      when oxytocin is given early in the estrous cycle.
AB  - The objective of this study was to determine whether PGE1 or PGE2 prevents a
      premature luteolysis when oxytocin is given on Days 1 to 6 of the ovine estrous
      cycle. Oxytocin given into the jugular vein every 8 hours on Days 1 to 6
      postestrus in ewes decreased (P <= 0.05) luteal weights on Day 8 postestrus.
      Plasma progesterone differed (P <= 0.05) among the treatment groups; toward the
      end of the experimental period, concentrations of circulating progesterone in the
      oxytocin-only treatment group decreased (P <= 0.05) when compared with the other
      treatment groups. Plasma progesterone concentrations in ewes receiving PGE1 or
      PGE1 + oxytocin were greater (P <= 0.05) than in vehicle controls or in ewes
      receiving PGE2 or PGE2 + oxytocin and was greater (P <= 0.05) in all treatment
      groups receiving PGE1 or PGE2 than in ewes treated only with oxytocin. Chronic
      intrauterine treatment with PGE1 or PGE2 also prevented (P <= 0.05) oxytocin
      decreases in luteal unoccupied and occupied LH receptors on Day 8 postestrus.
      Oxytocin given alone on Days 1 to 6 postestrus in ewes advanced (P <= 0.05)
      increases in PGF2alpha in inferior vena cava or uterine venous blood. PGE1 or
      PGE2 given alone did not affect (P >= 0.05) concentrations of PGF2alpha in
      inferior vena cava and uterine venous blood when compared with vehicle controls
      or oxytocin-induced PGF2alpha increases (P <= 0.05) in inferior vena cava or
      uterine venous blood. We concluded that PGE1 or PGE2 prevented oxytocin-induced
      premature luteolysis by preventing a loss of luteal unoccupied and occupied LH
      receptors.

PMID- 24908338
TI  - Ruptures of the device landing zone in patients undergoing transcatheter aortic
      valve implantation: an analysis of TAVI Karlsruhe (TAVIK) patients.
AB  - BACKGROUND: Aortic rupture of the device landing zone is a rare complication of
      transcatheter aortic valve implantation (TAVI) and it is associated with
      significant mortality. METHODS: This study reports on the experience of a single
      center in a case series of more than 1,000 implants. We explored patient and
      procedural characteristics aiming at identifying variables that increase the risk
      for aortic root rupture. RESULTS: Among a total of 1,000 TAVI procedures, six
      patients (0.6 %) had a rupture of the device landing zone. Five of these patients
      received the balloon-expandable Edwards SAPIEN valve (5/813; 0.62 %) of which
      four had a supraannular and one a subannular rupture. One patient received the
      self-expanding Medtronic CoreValve (1/199; 0.5 %; p = n.s. vs. SAPIEN) and had an
      annular rupture. Factors that were associated with aortic rupture were: (1) the
      relative size of the valve compared with the aortic annulus and its geometric
      form; (2) the need for post-dilation of the new valve because of paravalvular
      leakage; and (3) the location and severity of calcification. We determined, to
      avoid aortic rupture, caution may be necessary in the presence of the following
      conditions: (1) flat sinuses of Valsalva and severe calcifications of either the
      body or the free edge of the aortic cusps (supraannular rupture); (2) an
      ellipsoid annulus and bulky calcifications on either the base of the cusps or the
      rim of the annulus (annular rupture); and (3) a narrow left-ventricular outflow
      tract (LVOT) and bulky calcification of the LVOT (subannular rupture). After
      considering these precautions, we observed no case of aortic root rupture in the
      following 600 cases. CONCLUSION: The data indicate that to reduce the frequency
      of aortic rupture, a careful pre-procedural planning appears essential to avoid
      this serious and potentially deleterious complication.

PMID- 24908340
TI  - Exploring the use of dynamic language assessment with deaf children, who use
      American Sign Language: Two case studies.
AB  - We describe a model for assessment of lexical-semantic organization skills in
      American Sign Language (ASL) within the framework of dynamic vocabulary
      assessment and discuss the applicability and validity of the use of mediated
      learning experiences (MLE) with deaf signing children. Two elementary students
      (ages 7;6 and 8;4) completed a set of four vocabulary tasks and received two 30
      minute mediations in ASL. Each session consisted of several scripted activities
      focusing on the use of categorization. Both had experienced difficulties in
      providing categorically related responses in one of the vocabulary tasks used
      previously. Results showed that the two students exhibited notable differences
      with regards to their learning pace, information uptake, and effort required by
      the mediator. Furthermore, we observed signs of a shift in strategic behavior by
      the lower performing student during the second mediation. Results suggest that
      the use of dynamic assessment procedures in a vocabulary context was helpful in
      understanding children's strategies as related to learning potential. These
      results are discussed in terms of deaf children's cognitive modifiability with
      implications for planning instruction and how MLE can be used with a population
      that uses ASL. LEARNING OUTCOMES: The reader will (1) recognize the challenges in
      appropriate language assessment of deaf signing children; (2) recall the three
      areas explored to investigate whether a dynamic assessment approach is sensitive
      to differences in deaf signing children's language learning profiles (3) discuss
      how dynamic assessment procedures can make deaf signing children's individual
      language learning differences visible.

PMID- 24908339
TI  - Clinical and echocardiographic correlates of serum copper and zinc in acute and
      chronic heart failure.
AB  - AIM: Emerging evidence suggests a pathophysiological role of micronutrient
      dyshomeostasis in heart failure, including promotion of adverse remodeling and
      clinical deterioration. We sought to evaluate serum copper (Cu) and zinc (Zn)
      levels in acute (AHF) and chronic (CHF) heart failure. METHODS: We studied 125
      patients, 71 % male, aged 69 +/- 11 years, 37 % with preserved left ventricular
      ejection fraction (LVEF >=40 %) (HFPEF), including 81 with AHF and 44 with CHF;
      21 healthy volunteers served as controls. Serum Cu and Zn levels were determined
      using air-acetylene flame atomic absorption spectrophotometry. RESULTS: Serum Cu
      levels were significantly higher in AHF (p = 0.006) and CHF (p = 0.002) patients
      compared to controls after adjusting for age, gender and comorbidities, whereas
      they did not differ between AHF and CHF (p = 0.840). Additionally, serum Cu in
      patients with LVEF <40 % was significantly higher compared to both controls (p <
      0.001) and HFPEF patients (p = 0.003). Serum Zn was significantly lower in AHF (p
      < 0.001) and CHF (p = 0.039) compared to control after adjusting for the above
      mentioned variables. Moreover, serum Zn was significantly lower in AHF than in
      CHF (p = 0.015). In multiple linear regression, LVEF (p = 0.033) and E/e ratio (p
      = 0.006) were independent predictors of serum Cu in total heart failure
      population, while NYHA class (p < 0.001) and E/e ratio (p = 0.007) were
      independent predictors of serum Zn. CONCLUSION: Serum Cu was increased both in
      AHF and CHF and correlated with LV systolic and diastolic function. Serum Zn, in
      contrast, was decreased both in AHF and CHF and independently predicted by
      clinical status and LV diastolic function.

PMID- 24908341
TI  - Oculomotor preparation as a rehearsal mechanism in spatial working memory.
AB  - There is little consensus regarding the specific processes responsible for
      encoding, maintenance, and retrieval of information in visuo-spatial working
      memory (VSWM). One influential theory is that VSWM may involve activation of the
      eye-movement (oculomotor) system. In this study we experimentally prevented
      healthy participants from planning or executing saccadic eye-movements during the
      encoding, maintenance, and retrieval stages of visual and spatial working memory
      tasks. Participants experienced a significant reduction in spatial memory span
      only when oculomotor preparation was prevented during encoding or maintenance. In
      contrast there was no reduction when oculomotor preparation was prevented only
      during retrieval. These results show that (a) involvement of the oculomotor
      system is necessary for optimal maintenance of directly-indicated locations in
      spatial working memory and (b) oculomotor preparation is not necessary during
      retrieval from spatial working memory. We propose that this study is the first to
      unambiguously demonstrate that the oculomotor system contributes to the
      maintenance of spatial locations in working memory independently from the
      involvement of covert attention. 

PMID- 24908342
TI  - Distributional structure in language: contributions to noun-verb difficulty
      differences in infant word recognition.
AB  - What makes some words easy for infants to recognize, and other words difficult?
      We addressed this issue in the context of prior results suggesting that infants
      have difficulty recognizing verbs relative to nouns. In this work, we highlight
      the role played by the distributional contexts in which nouns and verbs occur.
      Distributional statistics predict that English nouns should generally be easier
      to recognize than verbs in fluent speech. However, there are situations in which
      distributional statistics provide similar support for verbs. The statistics for
      verbs that occur with the English morpheme -ing, for example, should facilitate
      verb recognition. In two experiments with 7.5- and 9.5-month-old infants, we
      tested the importance of distributional statistics for word recognition by
      varying the frequency of the contextual frames in which verbs occur. The results
      support the conclusion that distributional statistics are utilized by infant
      language learners and contribute to noun-verb differences in word recognition. 

PMID- 24908343
TI  - How selfish is memory for cheaters? Evidence for moral and egoistic biases.
AB  - We remember very well when another person has cheated us, but is this due to the
      cheating's immorality or due to its negative consequences? Theories claiming that
      reputational memory helps retaliate cheating imply that we should be sensitive
      both to the norm violation and to the personal consequences of another person's
      cheating. In the present study, faces were presented with descriptions of immoral
      and moral behavior. In contrast to previous studies, the morality and the
      personal consequences of the behaviors were orthogonally manipulated (both
      cheating and trustworthy behavior could lead to personal benefits or costs). In a
      surprise memory test, participants were required to remember whether the faces
      were associated with moral or immoral behaviors, or with personal benefits or
      costs. Overall, the morality of the behaviors was better remembered than were the
      personal consequences of the same behaviors. However, the immorality of morally
      questionable behaviors was well remembered when associated with personal costs,
      and poorly remembered when associated with personal benefits. Apparently,
      people's categorization of the social environment is based on moral judgments,
      but also reflects self-serving biases. 

PMID- 24908344
TI  - Adenovirus: current epidemiology and emerging approaches to prevention and
      treatment.
AB  - Infections caused by adenoviruses are associated with significant morbidity and
      mortality in both hematopoietic stem cell and solid organ transplant recipients.
      The risk seems to be highest in allogeneic hematopoietic stem cell transplant
      recipients as well as heart, lung and small-bowel transplant recipients.
      Management of these infections may be difficult and includes reduction of
      immunosuppression whenever possible combined sometimes with antiviral therapy
      (mainly cidofovir). The currently available antiviral therapy is limited by the
      need for intravenous administration, potentially significant renal and
      hematologic toxicities. New emerging therapies such as brincidofovir and
      transfusion of adenovirus-specific T-lymphocytes may increase the available
      armamentarium for these potentially life-threatening infections. 

PMID- 24908345
TI  - Garbage on, garbage off: new insights into plasma membrane protein quality
      control.
AB  - Maintenance of cellular protein quality - by restoring misfolded proteins to
      their native state and by targeting terminally misfolded or damaged proteins for
      degradation - is a critical function of all cells. To ensure protein quality,
      cells have evolved various organelle-specific quality control mechanisms
      responsible for recognizing and responding to misfolded proteins at different
      subcellular locations of the cell. Recently, several publications have begun to
      elucidate mechanisms of quality control that operate at the plasma membrane (PM),
      recognizing misfolded PM proteins and targeting their endocytic trafficking and
      lysosomal degradation. Here, I discuss these recent developments in our
      understanding of PM quality control mechanisms and how they relate to global
      protein quality control strategies in the cell. 

PMID- 24908346
TI  - News from the caves: update on the structure and function of caveolae.
AB  - Recent data from the study of the cell biology of caveolae have provided insights
      both into how these flask-shaped invaginations of the plasma membrane are formed
      and how they may function in different contexts. This review discusses
      experiments that analyse the composition and ultrastructural distribution of
      protein complexes responsible for generating caveolae, that suggest functions for
      caveolae in response to mechanical stress or damage to the plasma membrane, that
      show that caveolae may have an important role during the signalling events for
      regulation of metabolism, and that imply that caveolae can act as endocytic
      vesicles at the plasma membrane. We also highlight unexpected roles for caveolar
      proteins in regulating circadian rhythms and new insights into the way in which
      caveolae may be involved in fatty acid uptake in the intestine. Current
      outstanding questions in the field are emphasised. 

PMID- 24908347
TI  - [Burnout and teamwork in primary care teams].
AB  - OBJECTIVE: To estimate the prevalence of burnout and the perception of teamwork
      in Primary Care teams from Barcelona. DESIGN: Multicenter cross-sectional.
      LOCATION: Primary Health Care Teams from Barcelona. Institut Catala de la Salut.
      PARTICIPANTS: All permanent employees or temporary professionals of all
      categories from 51 teams (N=2398). A total of 879 responses (36.7%) were
      obtained. MEASUREMENTS: The Maslach Burnout Inventory questionnaire, with 3
      dimensions, was sent by emotional exhaustion (AE), depersonalization (DP), and
      personal accomplishment (RP). Burnout is considered present when two or more
      dimensions scored high marks. Perception of teamwork and evaluation of leaders
      was evaluated using an ad hoc questionnaire. RESULTS: The prevalence of burnout
      was17.2% (two or more dimensions affected), and 46.2% had at least one of the
      three dimensions with a high level. A high level of AE was found in 38.2%, of DP
      in 23.8%, and 7.7% had low RP. Almost half (49.2%) believe that teamwork is
      encouraged in their workplace. Social workers overall, have a higher average of
      dimensions affected at a high level, followed by administrative personnel,
      dentists, doctors and nurses (p<0.001). Permanent staff have a greater degree of
      emotional exhaustion (p<0.002). Those who rated their leaders worst and least
      rated teamwork had more emotional exhaustion, depersonalization and higher level
      of burnout in general (p<0.001). CONCLUSIONS: The level of burnout among
      professionals is considerable, with differences existing between occupational
      categories. Teamwork and appreciating their leaders protect from burnout.

PMID- 24908348
TI  - Maximized left atrial dome approach for left atrial tumor resection.

PMID- 24908349
TI  - Ventricular and pulmonary vascular remodeling induced by pulmonary overflow in a
      chronic model of pretricuspid shunt.
AB  - OBJECTIVES: Current preclinical models of pulmonary arterial hypertension do not
      reproduce the clinical characteristics of congenital heart anomalies. Aortocaval
      shunt is relevant to a variety of clinical conditions. The pathophysiology and
      possible determination of pulmonary hypertension in this model are still
      undefined. METHODS: A method to create a standardized and reproducible aortocaval
      shunt was developed in rats. After creation of the shunt, the animals were
      followed up for 20 weeks and a sham laparotomy was used as a control. The chronic
      effects of volume overload on the right and left ventricles and pulmonary
      hemodynamic modifications were evaluated by biventricular catheterization,
      echocardiography, and magnetic resonance. Pulmonary vascular changes were defined
      by histology. RESULTS: An increased right ventricular end-diastolic area was
      confirmed by echocardiography. Left ventricular overload and decreased
      biventricular ejection fraction were demonstrated by magnetic resonance after 20
      weeks in the shunt group compared with the controls (left ventricle, 50% +/- 5%
      vs 62% +/- 3%, P = .029; right ventricle, 53% +/- 2% vs 65% +/- 2%, P = .036).
      Preload recruitable stroke work of left and right ventricles decreased after 20
      weeks in shunt rats (left ventricle: 36 +/- 7 vs 98 +/- 5, P = .004; right
      ventricle: 19 +/- 2 vs 32 +/- 9, P = .047). At the same time point,
      catheterization showed that effective pulmonary arterial elastance was increased
      only in the shunt group (1.29 +/- 0.20 vs 0.14 +/- 0.06 mm Hg/MUL; P = .004).
      Histology showed medial hypertrophy, small artery luminal narrowing, and
      occlusion. CONCLUSIONS: The aortocaval shunt model reliably produces right
      ventricular volume overload and secondary pulmonary hypertension. Due to a
      combination of left ventricular dysfunction and pulmonary overflow, the pulmonary
      hypertension produced shows features similar to those found in patients with
      chronic atrial-level shunt.

PMID- 24908350
TI  - Antegrade versus retrograde cerebral perfusion for hemiarch replacement with deep
      hypothermic circulatory arrest: does it matter? A propensity-matched analysis.
AB  - OBJECTIVE: The choice of cerebral perfusion strategy for aortic arch surgery has
      been debated, and the superiority of antegrade (ACP) or retrograde (RCP) cerebral
      perfusion has not been shown. We examined the early and late outcomes for ACP
      versus RCP in proximal (hemi-) arch replacement using deep hypothermic
      circulatory arrest (DHCA). METHODS: A retrospective analysis of a prospectively
      maintained database was performed for all patients undergoing elective and
      nonelective hemiarch replacement at a single referral institution from June 2005
      to February 2013. Total arch cases were excluded to limit the analysis to shorter
      DHCA times and a more uniform patient population for whom clinical equipoise
      regarding ACP versus RCP exists. A total of 440 procedures were identified, with
      360 (82%) using ACP and 80 (18%) using RCP. The endpoints included 30-day/in
      hospital and late outcomes. A propensity score with 1:1 matching of 40 pre- and
      intraoperative variables was used to adjust for differences between the 2 groups.
      RESULTS: All 80 RCP patients were propensity matched to a cohort of 80 similar
      ACP patients. The pre- and intraoperative characteristics were not significantly
      different between the 2 groups after matching. No differences were found in 30
      day/in-hospital mortality or morbidity outcomes. The only significant difference
      between the 2 groups was a shorter mean operative time in the RCP cohort (P =
      .01). No significant differences were noted in late survival (P = .90).
      CONCLUSIONS: In proximal arch operations using DHCA, equivalent early and late
      outcomes can be achieved with RCP and ACP, although the mean operative time is
      significantly less with RCP, likely owing to avoidance of axillary cannulation.
      Questions remain regarding comparative outcomes with straight DHCA and lesser
      degrees of hypothermia.

PMID- 24908351
TI  - Paraplegia prevention by oral pretreatment with memantine in a rabbit model.
AB  - OBJECTIVE: To evaluate the role of memantine (N-methyl-d-aspartate receptor
      antagonist) pretreatment for the prevention of spinal cord ischemia after
      infrarenal aortic clamping in a rabbit model. METHODS: Thirty New Zealand White
      rabbits were divided into 5 different groups of 6 rabbits. Groups 60-7 and 60-5
      received oral memantine 60 mg once a day for 7 and 5 days, respectively, and
      groups 30-5 and 30-3 received oral memantine 30 mg once a day for 5 and 3 days,
      respectively, all before surgery. Group C (control) received normal feeds without
      memantine. A paraplegic model was created by clamping both the aorta and the
      inferior vena cava infrarenally and just proximal to their bifurcations for 45
      minutes. The modified Tarlov score, motor evoked potential (MEP), serum memantine
      concentration, and histopathology of the spinal cord were evaluated. RESULTS: The
      mean modified Tarlov scores were 4.2+/-1.3, 4.3+/-1.0, 4.2+/-1.3, 4.3+/-1.2, and
      0.8+/-1.6 in groups 60-7, 60-5, 30-5, 30-3, and C, respectively at 6, 24, 48, and
      72 hours (P<.009 for individual groups vs control). Percentage amplitude loss of
      MEP by the end of surgery was 29.5%+/-46.3%, 11.9%+/-28.0%, 30.0%+/-46.8%,
      16.7%+/-40.8%, and 81.8%+/-40.3% for the 5 groups, respectively (P=.049). After
      declamping, MEP reappeared in 83%, 100%, 83%, 83%, and 33% of cases in the 5
      groups, respectively (P=.073). The serum memantine level was similar in the 4
      memantine groups. Spinal cords were normal in most of the rabbits in groups 60-7,
      60-5, 30-5, and 30-3, but severely ischemic in most of the rabbits in group C
      (P=.041). CONCLUSIONS: Oral memantine pretreatment is protective against spinal
      cord ischemia, and can be an additional strategy for the prevention of paraplegia
      during thoracoabdominal aortic surgeries.

PMID- 24908352
TI  - Venovenous perfusion-induced systemic hyperthermia: five-day sheep survival
      studies.
AB  - OBJECTIVE: Since hyperthermia selectively kills lung cancer cells, we developed a
      venovenous perfusion-induced systemic hyperthermia system for advanced lung
      cancer therapy. Our objective was to test the safety and accuracy of our
      venovenous perfusion-induced systemic hyperthermia system in 5-day sheep survival
      studies, following Good Laboratory Practice standards. METHODS: Our venovenous
      perfusion-induced systemic hyperthermia system, which included a double-lumen
      cannula (Avalon Elite, Rancho Dominguez, Calif), a centrifugal pump (Bio-Pump
      560; Medtronic Inc, Minneapolis, Minn), a heat exchanger (BIOtherm; Medtronic
      Perfusion Systems, Brooklyn Park, Minn), and a heater/cooler (modified Blanketrol
      IIIl Cincinnati Subzero, Cincinnati, Ohio), was tested in healthy adult sheep
      (n=5). The perfusion circuit was primed with prewarmed Plasma-Lyte A (Baxter
      Healthcare Corp, Deerfield, Ill) and de-aired. Calibrated temperature probes were
      placed in the right and left sides of the nasopharynx, bladder, and blood in/out
      tubing in the animal. The double-lumen cannula was inserted through the jugular
      vein into the superior vena cava, with the tip in the inferior vena cava.
      RESULTS: Therapeutic core temperature (42 degrees C-42.5 degrees C), calculated
      from the right and left sides of the nasopharynx and bladder temperatures, was
      achieved in all sheep. Heating time was 21+/-5 minutes. Therapeutic core
      temperature was maintained for 120 minutes followed by a cooling phase (35+/-6
      minutes) to reach baseline temperature. All sheep recovered from anesthesia with
      spontaneous breathing within 4 hours. Arterial, pulmonary, and central venous
      pressures were stable. Transient increases in heart rate, cardiac output, and
      blood glucose occurred during hyperthermia but returned to normal range after
      venovenous perfusion-induced systemic hyperthermia termination. Electrolytes,
      complete blood counts, and metabolism enzymes were within normal to near normal
      range throughout the study. No significant venovenous perfusion-induced systemic
      hyperthermia-related hemolysis was observed. Neurologic assessment showed normal
      brain function all 5 days. CONCLUSIONS: Our venovenous perfusion-induced systemic
      hyperthermia system safely delivered the hyperthermia dose with no significant
      hyperthermia-related complications.

PMID- 24908353
TI  - Effects of nationwide addition of selenium to fertilizers on foods, and animal
      and human health in Finland: From deficiency to optimal selenium status of the
      population.
AB  - Despite different geological features the Nordic countries are generally selenium
      poor areas. In each country various factors such as food importation and life
      style determine the selenium (Se) intake. Due to an extremely low Se intake in
      the 1970s in Finland, 0.025 mg/day, an official decision was made in 1984 to
      supplement multinutrient fertilizers with Se in the chemical form of sodium
      selenate. Almost all fertilizers used in Finland since 1985 have contained Se.
      Currently all crop fertilizers contain 15 mg Se/kg. Finland is still the only
      country to take this country-wide measure. In a national monitoring programme,
      sampling of cereals, basic foodstuffs, feeds, fertilizers, soils, and human
      tissues has been carried out annually since 1985 by four governmental research
      organizations. Sampling of foods has been done four times per year and human
      blood has been obtained annually from the same (n=60) adults. The accuracy of
      analyses has been verified by annual interlaboratory quality control. During this
      programme the selenium concentration of spring cereals has increased on average
      15-fold compared with the level before the Se fertilization. The mean increase in
      the Se concentration in beef, pork and milk was 6-, 2- and 3-fold. In terms of
      Se, organically grown foods of plant origin are generally comparable to products
      produced before the Se supplementation of fertilizers. Milk from organically fed
      cows is 50% lower in Se than the usual milk. The average dietary human intake
      increased from 0.04 mg Se/day/10 MJ in 1985 to a present plateau of 0.08 mg
      Se/day/10 MJ, which is well above the current nutrition recommendations. Foods of
      animal origin contribute over 70% of the total daily Se intake. The mean human
      plasma Se concentration increased from 0.89 MUmol/L to a general level of 1.40
      MUmol/L that can be considered to be an optimal status. The absence of Se
      deficiency diseases and a reference population have made conclusions on the
      impact on human health difficult. However, the rates of cardiovascular diseases
      and cancers have remained similar during the pre- and post-supplementation
      indicating medical and life-style factors to be much stronger determinants than
      Se. The nationwide supplementation of fertilizers with sodium selenate is shown
      to be effective and safe in increasing the Se intake of the whole population.
      Also, the health of animals has improved.

PMID- 24908354
TI  - The growth-inhibitory and apoptosis-inducing effect of deferoxamine combined with
      arsenic trioxide on HL-60 xenografts in nude mice.
AB  - OBJECTIVE: The aim of this study is to investigate the growth-inhibitory and
      apoptosis-inducing effect of deferoxamine (DFO) combined with arsenic trioxide
      (ATO) on the human HL-60 xenografts in nude mice and its mechanism. METHOD: The
      highly tumorigenic leukemia cell line HL-60 cells were inoculated subcutaneously
      into nude mice to establish a human leukemia xenograft model. The HL-60 xenograft
      nude mice models were randomly divided into four groups: control (Normal saline,
      NS), 50mg/kg DFO, 3mg/kg ATO, the combined treatment (50mg/kg DFO+1.5mg/kg ATO)
      once HL-60 cells were inoculated. Tumor sizes, growth curves, inhibitory rates,
      cell apoptosis, and the expression of apoptosis related markers were measured to
      evaluate the tumor growth. RESULTS: Xenografted tumors were observed in all nude
      mice since the 5th day of inoculation. The inhibitory rates of tumor weight were
      2.67%, 10.69%, and 25.57% in DFO, ATO and combination therapy groups,
      respectively. The combination of DFO with ATO induces significantly more tumor
      cell apoptosis than either agent alone (p<0.05). The expression of NF-kappaBp65
      and survivin proteins decreased significantly while the expression of Caspase-3
      and Bax increased in the combination therapy group (p<0.05). Double
      immunofluorescence for Caspase-3 and NFkappaBp65 demonstrated an inverse
      relationship between Caspase-3-positive areas and NFkappaBp65-positive areas, as
      well as the co-localization of Bax and survivin in xenografted tumor cells.
      CONCLUSIONS: Combination of DFO and ATO has synergistic effects on tumor growth
      inhibition and apoptosis-inducing in vivo with no significant side effects. The
      DFO and ATO can up-regulate the expression of Caspase-3 and Bax, and down
      regulate the expression of NF-kappaBp65 and survivin, especially for their
      combination.

PMID- 24908355
TI  - Experimental investigations and finite element simulation of cutting heat in
      vibrational and conventional drilling of cortical bone.
AB  - Heat generated during bone drilling could cause irreversible thermal damage,
      which can lead to bone necrosis or even osteomyelitis. In this study, vibrational
      drilling was applied to fresh bovine bones to investigate the cutting heat in
      comparison with conventional drilling through experimental investigation and
      finite element analysis (FEA). The influence of vibrational frequency and
      amplitude on cutting heat generation and conduction were studied. The
      experimental results showed that, compared with the conventional drilling,
      vibrational drilling could significantly reduce the cutting temperature in
      drilling of cortical bone (P<0.05): the cutting temperature tended to decrease
      with increasing vibrational frequency and amplitude. The FEA results also showed
      that the vibrational amplitude holds a significant effect on the cutting heat
      conduction. 

PMID- 24908356
TI  - Evaluation of a CT-based technique to measure the transfer accuracy of a
      virtually planned osteotomy.
AB  - Accurate transfer of a preoperatively planned osteotomy plane to the bone is of
      significance for corrective surgery, tumor resection, implant positioning and
      evaluation of new osteotomy techniques. Methods for comparing a preoperatively
      planned osteotomy plane with a surgical cut exist but the accuracy of these
      techniques are either limited or unknown. This paper proposes and evaluates a CT
      based technique that enables comparing virtual with actual osteotomy planes. The
      methodological accuracy and reproducibility of the technique is evaluated using
      CT-derived volume data of a cadaver limb, which serves to plan TKA osteotomies in
      3-D space and to simulate perfect osteotomies not hampered by surgical errors.
      The methodological variability of the technique is further investigated with
      repeated CT scans after actual osteotomy surgery of the same cadaver specimen.
      Plane displacement (derr) and angulation errors in the sagittal and coronal plane
      (betaerr, gammaerr) are measured with high accuracy and reproducibility (derr=
      0.11+/-0.06mm; betaerr=0.08+/-0.04 degrees , gammaerr=-0.03+/-0.03 degrees ). The
      proposed method for evaluating an osteotomy plane position and orientation has a
      high intrinsic accuracy and reproducibility. The method can be of great value for
      measuring the transfer accuracy of new techniques for positioning and orienting a
      surgical cut in 3-D space. 

PMID- 24908358
TI  - Aspirin may modify tumor microenvironment via antiplatelet effect.
AB  - High-quality evidence suggests that aspirin is a promising agent for cancer
      prevention and treatment. Direct inhibition of cyclooxygenase-2 (COX-2) pathway
      is generally thought to be the main mechanism by which aspirin inhibits cancer
      development. However, either pharmacological properties of aspirin or recent
      results of epidemiologic studies do not support that mechanism. To address this
      inconsistency, we hypothesize that antiplatelet effect of aspirin via inhibition
      of COX-1 may be one of potential mechanisms to inhibit carcinogenesis. Aberrant
      platelet activation will lead to promote hostility of tumor microenvironment by
      releasing an abundant array of angiogenesis regulators. Given the outstanding
      ability of antiplatelet, aspirin may restore balance of pro- and anti-angiogenic
      factors released from platelet to "normalize" tumor vasculature and shape tumor
      microenvironment to some extent, which will not only diminish tumor
      aggressiveness and progression, but also enhance the sensitivity to therapeutic
      treatment. Thus, targeting the platelet activation leading to alter tumor
      microenvironment may provide a novel way to tumor therapy. 

PMID- 24908357
TI  - Perceived barriers to mammography among underserved women in a Breast Health
      Center Outreach Program.
AB  - BACKGROUND: To investigate perceived barriers to mammography among underserved
      women, we asked participants in the Siteman Cancer Center Mammography Outreach
      Registry-developed in 2006 to evaluate mobile mammography's effectiveness among
      the underserved-why they believed women did not get mammograms. METHODS: The
      responses of approximately 9,000 registrants were analyzed using multivariable
      logistic regression. We report adjusted odds ratios (OR) and 95% confidence
      intervals (CI) significant at 2-tailed P values less than .05. RESULTS: Fears of
      cost (40%), mammogram-related pain (13%), and bad news (13%) were the most
      commonly reported barriers. Having insurance was associated with not perceiving
      cost as a barrier (OR .44, 95% CI .40 to .49), but with perceiving fear of both
      mammogram-related pain (OR 1.39, 95% CI 1.21 to 1.60) and receiving bad news (OR
      1.38, 95% CI 1.19 to 1.60) as barriers. CONCLUSION: Despite free services,
      underserved women continue to report experiential and psychological obstacles to
      mammography, suggesting the need for more targeted education and outreach in this
      population.

PMID- 24908359
TI  - HBO: a possible supplementary therapy for oral potentially malignant disorders.
AB  - Oral potentially malignant disorders (OPMDs) are chronic inflammatory diseases in
      which cells suffer hypoxia referring to deprivation of adequate oxygen supply.
      Hyperbaric oxygen treatment (HBO), which can increase oxygen tension and delivery
      to oxygen-deficient tissue, is a supplementary therapy to improve or cure
      disorders involving hypoxia. Although the applications of HBO in wound healings,
      acute ischemic stroke, radiation-induced soft tissue injury and cancers are
      extensively reported, there are only few studies on their effect in OPMDs. Not
      only does HBO furnish oxygen-it also possesses potent anti-inflammatory
      properties. At the cellular level, HBO can decrease lymphocyte proliferation and
      promote apoptosis of fibroblasts. At the molecular level, it can decrease
      expression of HIF, ICAM-1, TNF-alpha, TGF-beta, and IFN-gamma, as well as
      increase vascular VEGF expression and angiogenesis. Thus, we hypothesize that HBO
      may contribute to treat OPMDs, including oral lichen planus, oral leukoplakia,
      and oral submucous fibrosis both at the cellular level and the molecular level,
      and that it would be a safe and inexpensive therapeutic strategy. 

PMID- 24908360
TI  - Time trends for injuries and illness, and their relation to performance in the
      National Basketball Association.
AB  - OBJECTIVES: To survey injury/illness in the National Basketball Association over
      a 25-year period and examine the relationship of injury/illness to team
      performance. DESIGN: A retrospective correlational design. METHODS: Trends were
      examined in reported numbers of players injured/ill during a season and games
      missed due to injury/illness from seasons ending in 1986 through 2005. This
      period was compared to years 2006-2010, when NBA teams were allowed to increase
      the total number of players on the team from 12 to 15. RESULTS: There was a
      highly significant trend (p<0.0001) of increasing numbers of players injured/ill
      and games missed from 1986 through 2005. After the team expansion in 2006, these
      rates fell abruptly by 13% and 39% respectively (both p<0.0001 compared to the
      previous 5-year period). We also found a significant inverse association between
      games missed due to injury/illness and percent games won (r=-0.29, p<0.0001).
      CONCLUSIONS: Results demonstrate an increased rate of injury in the National
      Basketball Association up until the expansion of team size in 2006. Following
      2006, team expansion was positively associated with decreased injury/illness
      rates. The latter finding suggests the importance of maintaining a healthy roster
      with respect to winning outcomes.

PMID- 24908361
TI  - Associations between sports participation and psychological difficulties during
      childhood: a two-year follow up.
AB  - OBJECTIVES: This paper assessed the associations between sports participation and
      the development of psychological strengths and difficulties during childhood.
      DESIGN: Two-year follow up study of a sample of 4042 Australian children who were
      followed from age 8 years to 10 years. METHODS: Parents reported children's
      participation in organised sports, and completed the Strengths and Difficulties
      Questionnaire. Univariate general linear models were used to examine the
      association between changes in sports participation and psychological strengths
      and difficulties at 10 years, adjusting for psychological strengths and
      difficulties at age 8. RESULTS: Children who maintained participation in sport
      had lower rates of parent-reported psychological difficulties at 10 years
      compared with children who dropped out of sport. Less internalising problems were
      also reported for children who participated in organised sports compared to
      children who dropped out of sports and children who did not participate in
      sports. These relationships did not differ by BMI, socioeconomic status, or
      parental education. CONCLUSIONS: Greater psychological difficulties are
      experienced by children who drop out of sports, and greater social and emotional
      problems are experienced by children who drop out of sports and who do not
      participate in organised sports. Due consideration should be given to the quality
      and implementation of sporting programs to ensure that they provide benefits to
      mental health. Due consideration should also be given to the potential
      psychological difficulties being experienced by children who drop out of
      organised sports as a higher level of psychological difficulties may be
      experienced prior to or subsequent to dropout.

PMID- 24908362
TI  - Will technological modernization for power generation at an oil refinery diminish
      the risks from air pollution to the Atlantic Rainforest in Cubatao, SE Brazil?
AB  - We assessed the level of atmospheric contamination by S, N and metals before,
      during and after the installation of a new thermoelectric plant that provides
      power to an oil refinery in Cubatao, SE Brazil. We measured the foliar
      accumulation in Lolium multiflorum "Lema" with the aim of evaluating risks to the
      Atlantic Rainforest that grows in the region. Al, Co, Cr, Cu, K, N, Ni, S, V and
      Zn were appropriate markers of the new air contamination profile associated with
      the modern technology. With the exception of V, the leaf contents of these
      elements significantly increased between the pre-operation to post-operation
      phases (Al, Co, N, K, S), or only during the transition phase (Zn, Cu, Cr, Ni),
      and returned to the previous levels after the total shutdown of the old system.
      Therefore, the expected environmental gain was not achieved with the installation
      of the new technology. 

PMID- 24908363
TI  - The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces
      apoptosis of urothelial cancer cells.
AB  - BACKGROUND: Activation of Rho, one of the small GTPases, and its major downstream
      target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We
      previously showed that elevation of Rho and ROCK expression was associated with
      tumor invasion, metastasis, and an unfavorable prognosis in patients with
      urothelial cancer of the bladder or upper urinary tract. METHODS: We investigated
      the effects of a ROCK inhibitor on the growth, migration, and apoptosis of
      bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by
      measuring its GTP-bound active form and assessed the expression of ROCK to
      explore the underlying molecular mechanisms. RESULTS: Lysophosphatidic acid (LPA)
      and geranylgeraniol (GGOH) induced an increase of cell proliferation and
      migration in association with promotion of RhoA activity and upregulation of ROCK
      expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation
      and migration, and also induced apoptosis in a dose-dependent manner. HA-1077
      dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect
      RhoA activity. CONCLUSIONS: These findings suggest that ROCK could be a potential
      molecular target for the treatment of urothelial cancer.

PMID- 24908364
TI  - Teratoma with malignant transformation: report of three cases and review of the
      literature.
AB  - Teratoma with malignant transformation is an uncommon, very aggressive germ cell
      tumor that has undergone transformation of a somatic teratomatous component to a
      histologic type identical to a somatic malignancy. We review the clinical
      presentation, imaging appearances, and prognosis of this entity and highlight its
      aggressive behavior by reporting on three patients with metastatic testicular
      nonseminomatous germ cell tumor with histologically proved malignant
      transformation. 

PMID- 24908365
TI  - Detection of axillary lymph node metastasis with diffusion-weighted MR imaging.
AB  - The feasibility of detecting axillary lymph node (LN) metastases with diffusion
      weighted MR imaging was retrospectively evaluated. The relative ADC (with b
      values of 0 and 1000 s/mm(2)) between LNs in each axillary space was calculated
      (n=75). The area, the long and short diameter of the metastatic LNs were compared
      to those of non-metastatic LNs. The relative ADC value of metastatic LNs was
      significantly lower than that of non-metastatic LNs (P=.00). The long and short
      diameter LN diagnostic performance was superior to that of mean ADC and relative
      ADC (AUC: 0.84, 0.80 versus 0.64, 0.03), suggesting usefulness of diameter over
      ADC. 

PMID- 24908366
TI  - Chiasmitis caused by Mycobacterium haemophilum in an immunocompromised adult.
AB  - We report a case of chiasmitis caused by a rare nontuberculous mycobacterium in
      an immunocompromised patient. A 44-year-old man with a history of AIDS presented
      with recurrent vision loss and headache. Magnetic resonance imaging (MRI)
      demonstrated an enhancing mass involving the optic chiasm. Histopathologic and
      microbiological evaluation revealed infection with Mycobacterium haemophilum.
      While combination antimicrobial and steroid therapy contributed to improvement in
      his vision, the patient's symptoms recurred. Follow-up MRI showed extension of
      infection to the hypothalamus and leptomeninges, indicative of basilar
      meningitis. MRI is a valuable tool for early diagnosis of chiasmitis as well as
      for monitoring infection progression and treatment response. 

PMID- 24908367
TI  - Diffusion tensor imaging of the sural nerve in normal controls.
AB  - OBJECTIVE: To develop a diffusion tensor imaging (DTI) protocol for assessing the
      sural nerve in healthy subjects. METHODS: Sural nerves in 25 controls were imaged
      using DTI at 3T with 6, 15, and 32 gradient directions. Fractional anisotropy
      (FA) and apparent diffusion coefficient (ADC) were computed from nerve regions of
      interest co-registered with T2-weighted images. RESULTS: Coronal images with
      0.5(RL)* 2.0(FH)* 0.5(AP)mm(3) resolution successfully localized the sural nerve.
      FA maps showed less variability with 32 directions (0.559 +/- 0.071) compared to
      15(0.590 +/- 0.080) and 6(0.659 +/- 0.109). CONCLUSIONS: Our DTI protocol was
      effective in imaging sural nerves in controls to establish normative FA/ADC, with
      potential to be used non-invasively in diseased nerves of patients.

PMID- 24908368
TI  - Feasible Method to enable clear visualization of suspected bladder cancer with
      18F-FDG PET/CT.
AB  - PURPOSE: To evaluate value of a new method in detecting bladder lesion with (18)F
      FDG PET/CT. METHODS: Routine and delayed scans of 14 patients were
      retrospectively studied. All these bladder lesions were confirmed by pathology.
      By increasing display threshold of SUVmax, routine images were analyzed for the
      second time. RESULTS: Of 12 (18)F-FDG-avid cases, 10 cases were confirmed to be
      primary bladder carcinoma, 2 false-positive cases were inflammation. There were
      25% positive cases on routine display and 50% on display with increased SUVmax
      threshold. CONCLUSION: The method can effectively increase the sensitivity and
      accuracy in detecting bladder cancer with (18)F-FDG PET/CT.

PMID- 24908369
TI  - Jugular vein invasion rate in surgically operated paragangliomas: a multimodality
      retrospective study.
AB  - PURPOSE: To assess the rate of jugular vein (JV) invasion by paragangliomas and
      imaging's ability to predict invasion. METHODS: Imaging studies of patients with
      paragangliomas were evaluated for JV invasion. Rates of invasion by different
      paragangliomas and each modality's accuracy were determined. RESULTS: JV invasion
      occurred in 11/11 glomus jugulares (GJs), 3/5 glomus vagales, and 2/8 carotid
      body tumors. Accuracy for magnetic resonance imaging (92.3%), computed tomography
      (92.3%), and digital subtraction angiography (94.1%) was comparable. CONCLUSIONS:
      JV invasion is characteristic of but not specific to GJs. All modalities show
      high accuracy in detecting invasion.

PMID- 24908370
TI  - Forkhead box protein P1 is a useful marker for the diagnosis of mucinous minimal
      deviation adenocarcinoma of uterine cervix.
AB  - Mucinous minimal deviation adenocarcinoma (MDA) is a rare highly differentiated
      tumor of uterine cervix, of which the confusing histopathology resembling some
      benign lesions usually makes difficulty for pathologic diagnosis. The expression
      of forkhead box protein P1 (FOXP1) is found in some kinds of human tumors and is
      considered to be associated with the progression of the tumors. The purpose of
      this study is to detect the FOXP1 expression in MDA and evaluate its possible
      role in the diagnosis of MDA. Twenty-two MDA cases and 20 control cases
      consisting of 10 cases of lobular endocervical glandular hyperplasia and 10 cases
      of normal endocervical tissue were included in this study. All available clinical
      data were collected and immunostaining for FOXP1, carcinoembryonic antigen (CEA),
      human milk fat globule antigen 1 (HMFG1), estrogen receptor, and progesterone
      receptor were performed on these cases. The nuclear/cytoplasmic expression of
      FOXP1 was found in 18 of 22 MDA cases while in 1 of 20 control cases, which
      showed statistical significance (P = .000). The cytoplasmic CEA expression was
      found in 14 of 22 MDA cases and 2 of 20 control cases (P = .000), whereas
      cytoplasmic HMFG1 expression was found in 10 of 22 MDA cases and 4 of 20 control
      cases (P = .081). No statistical difference was found between FOXP1 and CEA
      expression (P = .083) or between FOXP1 and HMFG1 expression (P = .375) in MDA.
      Neither estrogen receptor nor PR expression was found in MDA. The significant
      expression of FOXP1 in MDA may be helpful to some extent in the pathologic
      diagnosis of cervical MDA. A widened observation range and further researches are
      needed to elucidate the potential mechanism. 

PMID- 24908371
TI  - Pulmonary adenofibroma: clinicopathological study of 3 cases of a rare benign
      lung lesion and review of the literature.
AB  - Pulmonary adenofibroma is a rare benign biphasic tumor of the lung composed of
      epithelial and stromal components. We report 3 cases of this unusual lesion of
      lung in a male (25 years old) and 2 female (40 and 55 years old) patients.
      Breathlessness on exertion and mild left-sided chest pain of 1 month's duration
      were the main concerns in 2 patients, whereas the third had cough and hemoptysis
      for 3 months. Chest radiograph and computed tomography scan revealed a well
      circumscribed, subpleural homogenous mass in left lower chest fields in 2 cases
      and solid-cystic lesion in left upper lobe in the third patient. All 3 patients
      underwent lobectomy, following biopsy in 2 cases. Histology revealed a well
      circumscribed lesion composed of complex glandlike spaces lined by cuboidal to
      columnar epithelium surrounded by a hyalinized spindle-cell fibroblastic
      proliferation reminiscent of adenofibroma of the female genital tract or
      fibroadenoma of the breast. Immunohistochemical examination supported the
      diagnosis of a benign pulmonary adenofibroma. All 3 patients were are alive and
      doing well with no evidence of recurrent or metastatic disease. Diagnosis on
      biopsy can be challenging and may be misinterpreted as well-differentiated
      adenocarcinoma with extensive fibrosis or low-grade sarcoma. Frozen-section
      consultation will be a valuable adjunct in planning for limited lung resection of
      this benign lung lesion. Although we described 3 cases of pulmonary adenofibroma,
      still this is the largest published series of this rare entity till date. The
      possible histogenesis and various differential diagnoses are discussed along with
      literature review. 

PMID- 24908372
TI  - Drosophila developmental biology methods.

PMID- 24908373
TI  - Short-term cognitive changes after surgery in patients with unilateral mesial
      temporal lobe epilepsy associated with hippocampal sclerosis.
AB  - We investigated the short-term postoperative cognitive function of patients with
      unilateral mesial temporal lobe epilepsy associated with hippocampal sclerosis
      (MTLE/HS). Fourteen unilateral MTLE/HS patients who had undergone selective
      amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) were enrolled.
      Cognitive functions related to the frontal and temporal lobes were evaluated
      using a battery of neuropsychological tests administered before surgery and
      3months after surgery. The battery included the Verbal Fluency Test (VFT), Boston
      Naming Test (BNT), Stroop Color-Word Test (TST), Trail Making Test (TMT) and
      Wechsler Memory Scale (WMS). MTLE/HS patients demonstrated significantly improved
      postoperative performance on the TST regardless of the surgical method or side of
      resection. There was no significant difference in any of the other
      neuropsychological tests before and after surgery. After left-side resection,
      performance on the VFT and the TMT-B was worse than at baseline. After right-side
      resection, performance on the VFT and WMS short-term memory improved; however,
      these differences were not statistically significant. SAH patients exhibited
      improved TST performance but worse TMT-A performance; however, performance on all
      tests was not significantly different after surgery in ATL patients. In summary,
      MTLE/HS patients demonstrated improved frontal lobe-related cognitive function
      after surgery, but no such improvement in temporal lobe-related function was
      observed. Based on cognitive evaluation, right-sided MTLE/HS patients may be more
      appropriate surgical candidates than left-sided MTLE/HS patients. SAH may not be
      better than ATL in improving cognitive function. We hypothesise that
      postoperative cognitive changes depend on whether the excised cerebral regions
      are related to the neuropsychological functions examined by specific assessment
      instruments. 

PMID- 24908374
TI  - Modern treatment of 84 newly diagnosed craniopharyngiomas.
AB  - There is debate regarding the appropriate treatment for craniopharyngiomas, which
      often present symptomatically given their proximity to critical brain structures,
      and pose significant surgical challenges. The goal of this study is to identify
      which patient and tumor characteristics are associated with specific preoperative
      symptoms, surgical complications, patient outcomes, and tumor recurrence in order
      to guide craniopharyngioma treatment. We retrospectively identified 84 patients
      with newly diagnosed craniopharyngiomas treated at our institution from 1986
      2010. We used binary logistic regression and survival analysis to determine the
      effect of several variables (including sex, age, tumor size, location, surgical
      approach, and extent of resection) on preoperative symptoms and postoperative
      outcomes, including complication rates and tumor recurrence. Age and tumor
      location were associated with increased rates of preoperative symptoms, with
      children being more likely than adults to present with endocrine dysfunction, and
      intraventricular tumors being more likely than extraventricular tumors to present
      with headaches and hydrocephalus. A transcranial surgical approach was associated
      with 1.5 times higher rate of surgical complications than transsphenoidal
      surgery, while only intraventricular tumor location was associated with a poorer
      patient outcome. The main factor significantly associated with tumor recurrence
      was extent of resection. We conclude that intraventricular tumor location is most
      highly correlated with preoperative symptoms. If feasible, transsphenoidal
      approaches are preferred, as they result in fewer surgical complications, and
      gross total resections are optimal because they lead to lower rates of
      recurrence. When gross total resection is not possible, we favor multimodal
      treatment approaches. 

PMID- 24908375
TI  - Titanium mesh-assisted dural tenting for an expansile suboccipital cranioplasty
      in the treatment of Chiari 1 malformation.
AB  - Cerebellar ptosis and dural prolapse are known complications after posterior
      craniocervical decompression of Chiari 1 malformation (CM1), and are associated
      with larger craniectomies, epidural scarring and intradural adhesions. Although
      management of these complications has been well documented, little has been
      reported in regards to their prevention. We describe our variation of the
      posterior fossa decompression technique for CM1 using a titanium mesh-assisted
      dural tenting expansile cranioplasty to prevent both cerebellar ptosis and dural
      prolapse. A watertight dural augmentation patch is performed after posterior
      craniocervical decompression. A titanium mesh cranioplasty is performed to cover
      the superior aspect of the craniectomy. The duraplasty is then tented to the
      titanium mesh plate with several interrupted sutures. The titanium mesh plate was
      intended to prevent postoperative cerebellar ptosis or sag, while the dural
      tenting was performed to prevent delayed collapse and restenosis of the cistern
      magna. Four patients with CM1 underwent this technique without complication.
      Postoperative MRI did not demonstrate cerebellar ptosis, restenosis or collapse
      of the cisterna magna. The expansile suboccipital cranioplasty with titanium mesh
      assisted dural tenting technique is a simple and efficient strategy that may be
      useful to prevent cerebellar ptosis and dural prolapse and maintain the patency
      of the surgically created neo-cisterna magna. 

PMID- 24908376
TI  - Efficacy of systemic bisphosphonate delivery on osseointegration of implants
      under osteoporotic conditions: lessons from animal studies.
AB  - BACKGROUND: The aim was to systematically review the role of systemic
      bisphosphonate (BP) delivery on osseointegration of implants under osteoporotic
      conditions. METHODS: The addressed focused question was "Does systemic BP
      delivery enhance osseointegration of implants under osteoporotic conditions?"
      PubMed/MEDLINE and Google-Scholar databases were searched from 1994 up to and
      including December 2013 using different combinations of the following keywords:
      "bone to implant contact", "implant", "bisphosphonate", "osseointegration" and
      "osteoporosis". Review articles, case-reports, commentaries, letters to the
      Editor, unpublished articles and articles published in languages other than
      English were excluded. RESULTS: Fifteen animal studies fulfilled our eligibility
      criteria. Osteoporotic conditions were induced via bilateral ovariectomy (OVX).
      BPs used in the studies were ibandronate, zoledronic acid and alendronate.
      Results from 12 studies showed that systemic BP delivery significantly increased
      bone volume and bone-to-implant contact under osteoporotic conditions. Two
      studies reported no significant difference in osseointegration among OVX animals
      with and without systemic BP delivery. In one study, systemic BP delivery
      negatively influenced implant osseointegration. Rough-surfaced and polished
      implants were used in 11 and one study respectively. In 3 studies implant surface
      characteristics remained unclear. CONCLUSION: Within the limits of the present
      study, it is concluded that systemic BP delivery enhances implant
      osseointegration in animals with induced osteoporotic conditions. However, in a
      clinical scenario, the potential risk of BP related ONJ in osteoporotic patients
      undergoing dental implant therapy cannot be disregarded.

PMID- 24908377
TI  - Dietary Spirulina (Arthrospira platensis) and Thyme (Thymus vulgaris)
      supplementation to growing rabbits: effects on raw and cooked meat quality,
      nutrient true retention and oxidative stability.
AB  - The study evaluated the effect of Spirulina and Thyme dietary supplementation on
      rabbit meat quality, nutrient true retention and protection against oxidative
      stress. Rabbits in the control group (C-C) received a non-supplemented pellet
      throughout the experiment (5-11weeks of age). In the other groups, the pellet
      contained 5% Spirulina (S), 3% Thyme (T), or both (ST) for either the entire
      (groups S-S, T-T, ST-ST) or only the final part of the growing period (8-11weeks:
      groups C-S, C-T, C-ST). Spirulina supplementation increased the gamma-linolenic
      acid content of rabbit meat, whereas Thyme improved the oxidative stability of
      raw and freeze-dried meat. 

PMID- 24908378
TI  - Editorial overview: Cell nucleus: the nucleus: a dynamic organelle.

PMID- 24908379
TI  - Vigabatrin in dried plasma spots: validation of a novel LC-MS/MS method and
      application to clinical practice.
AB  - This paper presents a LC-MS/MS method for the determination of antiepileptic drug
      vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical
      structure, a pre-column derivatization procedure was performed, aiming to yield
      enhanced ionization efficiency and improved chromatographic behaviour. Propyl
      chloroformate, in the presence of propanol, was selected as the best
      derivatization reagent, providing a strong signal along with reasonable run time.
      A relatively novel sample collection technique, DPS, was utilized, offering easy
      sample handling and analysis, using a sample in micro amount (~5MUL). Derivatized
      vigabatrin and its internal standard, 4-aminocyclohexanecarboxylic acid, were
      extracted by liquid-liquid extraction (LLE) and determined in positive ion mode
      by applying two SRM transitions per analyte. A Zorbax Eclipse XDB-C8 column
      (150*4.6mm, 5MUm particle size) maintained at 30 degrees C, was utilized with
      running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v).
      Flow rate was 550MUL/min and total run time 4.5min. The assay exhibited excellent
      linearity over the concentration range of 0.500-50.0MUg/mL, which is suitable for
      the determination of vigabatrin level after per os administration in children and
      youths with epilepsy, who were on vigabatrin therapy, with or without co
      medication. Specificity, accuracy, precision, recovery, matrix-effect and
      stability were also estimated and assessed within acceptance criteria. 

PMID- 24908380
TI  - Effect of hawk-dove game on the dynamics of two competing species.
AB  - Outcomes of interspecific competition, and especially the possibility of
      coexistence, have been extensively studied in theoretical ecology because of
      their implications in community assemblages. During the last decades, the
      influence of different time scales through the local/regional dynamics of animal
      communities has received an increasing attention. Nevertheless, different time
      scales involved in interspecific competition can result form other processes than
      spatial dynamics. Here, we envision and analyze a new theoretical framework that
      couples a game theory approach for competition with a demographic model. We take
      advantage of these two time scales to derive a reduced model governing the total
      densities of the two populations and we study how these two time scales interfere
      and influence outcomes of species competition. We find that a competition process
      occurring on a faster time scale than demography yields a "priority effect" where
      the first species introduced outcompetes the other one. We then confirm previous
      findings stipulating that species coexistence is favored by large difference in
      time scales because the extinction/recolonization process. Our results then
      highlight that an integration of demographic and competition time scales at both
      local and regional levels is mandatory to explain communities assemblages and
      should become a research priority. 

PMID- 24908381
TI  - Plant metabolomics is not ripe for environmental risk assessment.
AB  - Metabolomics separates and detects small molecules and helps determine the
      composition of plant materials. This makes it appear to be a possible contributor
      to environmental risk assessment (ERA) of transgenic plants. Here we argue that,
      despite important advances in the technology, limited annotation and our limited
      knowledge of the role of metabolites in plant-environment interactions means that
      metabolomics is not yet ripe for ERA. 

PMID- 24908383
TI  - Enzyme-based biosilica and biocalcite: biomaterials for the future in
      regenerative medicine.
AB  - The oldest animals on Earth, sponges, form both the calcareous and the siliceous
      matrices of their spicules enzymatically. Until recently, it has been neglected
      that enzymes play crucial roles during formation of these biominerals. This
      paradigm shift occurred after the discovery that the enzyme silicatein, which
      catalyzes the polycondensation of silica, and the enzyme carbonic anhydrase (CA),
      which catalyzes the formation of bicarbonate (HCO3(-)/CaCO3), produce solid
      amorphous bioglass or biocalcite. This suggests that in mammals, biosilica and
      biocalcite can act anabolically during hydroxyapatite (HA) synthesis and bone
      formation. Biosilica and biocalcite are thus promising candidates for the
      fabrication of biomaterials for regenerative medicine. 

PMID- 24908382
TI  - Therapeutic protein aggregation: mechanisms, design, and control.
AB  - Although it is well known that proteins are only marginally stable in their
      folded states, it is often less well appreciated that most proteins are
      inherently aggregation-prone in their unfolded or partially unfolded states, and
      the resulting aggregates can be extremely stable and long-lived. For therapeutic
      proteins, aggregates are a significant risk factor for deleterious immune
      responses in patients, and can form via a variety of mechanisms. Controlling
      aggregation using a mechanistic approach may allow improved design of therapeutic
      protein stability, as a complement to existing design strategies that target
      desired protein structures and function. Recent results highlight the importance
      of balancing protein environment with the inherent aggregation propensities of
      polypeptide chains.

PMID- 24908384
TI  - The role of neighborhood income inequality in adolescent aggression and violence.
AB  - PURPOSE: Being a perpetrator or victim of assaults can have detrimental effects
      on the development and health of adolescents. Area-level income inequality has
      been suggested to be associated with crime and aggressive behavior. However, most
      prior research on this association has been ecological. Therefore, the purpose of
      this investigation was to describe the association between neighborhood-level
      income inequality and aggression and violence outcomes. METHODS: Data were
      collected from a sample of 1,878 adolescents living in 38 neighborhoods
      participating in the 2008 Boston Youth Survey. We used multilevel logistic
      regression models to estimate the association between neighborhood income
      inequality and attacking someone with a weapon, being attacked by someone with a
      weapon, being physically assaulted, being shown a gun by someone in the
      neighborhood, shot at by someone in the neighborhood, witnessing someone getting
      murdered in the past year, and having a close family member or friend murdered.
      Race and income inequality cross-level interactions were tested. Analyses were
      stratified by sex. RESULTS: Among nonblack boys, after adjusting for nativity,
      age, neighborhood-level income, crime, disorder, and proportion of the
      neighborhood that is black, income inequality was associated with an increased
      risk for committing acts of aggression and being a victim of violence. Among
      nonblack girls, those living in neighborhoods with high-income inequality were
      more likely to witness someone die a violent death in the previous year, in
      comparison to those in more equal neighborhoods. CONCLUSIONS: Income inequality
      appears to be related to aggression and victimization outcomes among nonblack
      adolescents living in Boston.

PMID- 24908385
TI  - Long-term predictors of blood pressure among adolescents during an 18-month
      school-based obesity prevention intervention.
AB  - PURPOSE: To evaluate the effectiveness of the HEROES (Healthy, Energetic, Ready,
      Outstanding, Enthusiastic Schools) initiative, a multicomponent school-based
      obesity prevention intervention based on the Centers for Disease Control and
      Prevention's coordinated school health approach, on the improvement of blood
      pressure (BP) and to determine long-term predictors of systolic and diastolic BP
      changes among high school students who were exposed to the intervention. METHODS:
      Biometric and behavioral data from high school students were analyzed at
      baseline, 6, 12, and 18 months (N = 847, three schools). The attrition rate at 18
      months was 26.1%. Sequential generalized estimating equation models were fit to
      the data using SAS 9.3, taking into account clustering effects within the same
      school and correlations within repeated measures. RESULTS: A significant downward
      trend was observed in systolic BP (p = .0006) and diastolic BP (p < .0001) among
      the students who were exposed to the HEROES initiative. The prevalence of
      hypertension decreased from 17.1% at baseline to 12.8% at 6 months (p < .0001),
      12.0% at 12 months (p < .0001), and 15.0% (p = .0024) at 18 months. Baseline body
      mass index, increases in body mass index percentiles, and increases of television
      viewing hours were associated with BP increases. Increases in frequencies of
      eating french fries or chips, skipping breakfast, and consuming supersize meals
      when eating fast food were predictive of systolic BP changes, not of diastolic BP
      changes. CONCLUSIONS: An 18-month multicomponent school-based obesity
      intervention program may be effectively used to decrease rates of high BP among
      adolescents.

PMID- 24908386
TI  - Multilevel examination of the association of urbanization with inflammation in
      Chinese adults.
AB  - We examine the associations between overall urbanicity and specific physical and
      social components of community-level urbanization with C-reactive protein (CRP)
      in adults participating in the China Health and Nutrition Study. Higher overall
      urbanicity and environment-related urbanicity component scores, including
      education, housing quality, and access to markets, were associated with elevated
      CRP in multilevel models controlling for clustering by community. These
      associations differed by age and gender and persisted after controlling for
      individual-level anthropometric, diet, and pathogenic risk factors. These results
      highlight the importance of place in relation to inflammation across the spectrum
      of rural and urban environments. 

PMID- 24908387
TI  - Differential long-term outcomes for voluntary and involuntary transition from
      injection to oral opioid maintenance treatment.
AB  - BACKGROUND: The most widely used maintenance treatment for opioid dependency is
      substitution with long-acting oral opioids. Treatment with injectable
      diacetylmorphine provides an opportunity for patients to stabilize and possibly
      transition to oral treatment, if clinically indicated. The aim of this study was
      to explore outcomes of individuals that received injectable diacetylmorphine and
      voluntarily transitioned to oral methadone. DESIGN AND METHODS: The North
      American Opiate Medication Initiative was a randomized controlled trial that
      compared the effectiveness of injectable diacetylmorphine (or hydromorphone) to
      oral methadone for long-term opioid-dependency. Treatment was provided for 12
      months with an additional 3 months for transition and weaning. Participants were
      followed until 24-months from randomization. Among the participants randomized to
      injectable treatments, a sub-group voluntarily chose to transition to oral
      methadone (n = 16) during the treatment period. Illicit heroin use and treatment
      retention were assessed at 24-months for those voluntarily and involuntarily
      transitioning (n = 95) to oral methadone. RESULTS: At 24-months, the group that
      voluntarily transitioned to oral methadone had higher odds of treatment retention
      (adjusted odds ratio = 5.55; 95% confidence interval [CI] = 1.11, 27.81; Chi
      square = 4.33, df = 1, p-value = 0.037) than the involuntary transition group. At
      24-months, the adjusted mean difference in prior 30 days of illicit heroin use
      for the voluntary, compared to the involuntary group was -5.58 (95% CI = -11.62,
      0.47; t-value = -1.83, df = 97.4, p-value = 0.070). CONCLUSIONS: Although the
      results of this study were based on small groups of self-selected (i.e., non
      randomized) participants, our data underlines the critical importance of
      voluntary and patient-centered decision making. If we had continued offering
      treatment with diacetylmorphine, those retained to injectable medication may have
      sustained the achieved improvements in the first 12 months. Diversified opioid
      treatment should be available so patients and physicians can flexibly choose the
      best treatment at the time. TRIAL REGISTRATION:  CLINICAL TRIAL REGISTRATION:
      NCT00175357.

PMID- 24908388
TI  - SAME-TT2R 2 score and vitamin K antagonist therapy.

PMID- 24908389
TI  - TH9 cells that express the transcription factor PU.1 drive T cell-mediated
      colitis via IL-9 receptor signaling in intestinal epithelial cells.
AB  - The molecular checkpoints that drive inflammatory bowel diseases are incompletely
      understood. Here we found more T cells expressing the transcription factor PU.1
      and interleukin 9 (IL-9) in patients with ulcerative colitis. In an animal model,
      citrine reporter mice had more IL-9-expressing mucosal T cells in experimental
      oxazolone-induced colitis. IL-9 deficiency suppressed acute and chronic colitis.
      Mice with PU.1 deficiency in T cells were protected from colitis, whereas
      treatment with antibody to IL-9 suppressed colitis. Functionally, IL-9 impaired
      intestinal barrier function and prevented mucosal wound healing in vivo. Thus,
      our findings suggest that the TH9 subset of helper T cells serves an important
      role in driving ulcerative colitis by regulating intestinal epithelial cells and
      that TH9 cells represent a likely target for the treatment of chronic intestinal
      inflammation.

PMID- 24908391
TI  - Drug-eluting stent technology: progress beyond the polymer.

PMID- 24908390
TI  - Quantitative and temporal requirements revealed for Zap70 catalytic activity
      during T cell development.
AB  - The catalytic activity of Zap70 is crucial for T cell antigen receptor (TCR)
      signaling, but the quantitative and temporal requirements for its function in
      thymocyte development are not known. Using a chemical-genetic system to
      selectively and reversibly inhibit Zap70 catalytic activity in a model of
      synchronized thymic selection, we showed that CD4(+)CD8(+) thymocytes integrate
      multiple, transient, Zap70-dependent signals over more than 36 h to reach a
      cumulative threshold for positive selection, whereas 1 h of signaling was
      sufficient for negative selection. Titration of Zap70 activity resulted in graded
      reductions in positive and negative selection but did not decrease the cumulative
      TCR signals integrated by positively selected OT-I cells, which revealed
      heterogeneity, even among CD4(+)CD8(+) thymocytes expressing identical TCRs
      undergoing positive selection.

PMID- 24908392
TI  - A misguided lead.

PMID- 24908394
TI  - Clinical evaluation of 292 Genesis II posterior stabilized high-flexion total
      knee arthroplasty: range of motion and predictors.
AB  - The primary aim of the study was to evaluate the range of motion and
      complications after Genesis II total knee arthroplasty with high-flexion tibia
      insert (TKA-HF). Furthermore, difference in knee flexion between high flexion and
      standard inserts was compared. The hypothesis was that knee flexion is better
      after high-flexion TKA. A total of 292 TKA-HF were retrospectively reviewed. Mean
      follow-up was 24.3 months. The range of motion was compared between TKA-HF (high
      flexion group) and a comparable cohort of 86 Genesis II TKA with a standard tibia
      insert (control group). Surgeries were performed by one experienced knee
      orthopedic surgeon. Knee flexion in the high-flexion group increased from 114.8
      degrees  preoperatively to 118.0 degrees  postoperatively (P < 0.01). Knee
      extension in the high-flexion group increased from -4.5 degrees  preoperatively
      to -0.4 degrees  after surgery (P < 0.01). Mean knee flexion was 5.52 degrees 
      (+/- 1.46 degrees ) better in the high-flexion group compared with the control
      group (P < 0.01). Preoperative range of motion, body mass index, diabetes
      mellitus and patellofemoral pain significantly influenced range of motion. Few
      complications occurred after TKA-HF. The Genesis II TKA-HF showed good short-term
      results with limited complications. Knee flexion after Genesis II TKA-HF was
      better compared with a standard tibia insert.

PMID- 24908393
TI  - Evolution of helix formation in the ribosomal Internal Transcribed Spacer 2
      (ITS2) and its significance for RNA secondary structures.
AB  - Helices are the most common elements of RNA secondary structure. Despite
      intensive investigations of various types of RNAs, the evolutionary history of
      the formation of new helices (novel helical structures) remains largely elusive.
      Here, by studying the nuclear ribosomal Internal Transcribed Spacer 2 (ITS2), a
      fast-evolving part of the eukaryotic nuclear ribosomal operon, we identify two
      possible types of helix formation: one type is "dichotomous helix formation"-
      transition from one large helix to two smaller helices by invagination of the
      apical part of a helix, which significantly changes the shape of the original
      secondary structure but does not increase its complexity (i.e., the total length
      of the RNA). An alternative type is "lateral helix formation"--origin of an extra
      helical region by the extension of a bulge loop or a spacer in a multi-helix loop
      of the original helix, which does not disrupt the pre-existing structure but
      increases RNA size. Moreover, we present examples from the RNA sequence
      literature indicating that both types of helix formation may have implications
      for RNA evolution beyond ITS2.

PMID- 24908395
TI  - Where is lupus hidden?
AB  - Systemic lupus erythematosus is a prototypic but heterogeneous autoimmune
      disease. The major clinical symptoms and signs are reviewed, as well as the main
      immunological abnormalities. Emphasis is put on the role of long-lived autoimmune
      plasma cells, not affected by current immunosuppressants and biologics, which are
      responsible for refractoriness and relapses. 

PMID- 24908396
TI  - Nucleosome assembly is required for nuclear pore complex assembly in mouse
      zygotes.
AB  - Packaging of DNA into nucleosomes not only helps to store genetic information but
      also creates diverse means for regulating DNA-templated processes. Attempts to
      reveal additional functions of the nucleosome have been unsuccessful, owing to
      cell lethality caused by nucleosome deletion. Taking advantage of the mammalian
      fertilization process, in which sperm DNA assembles into nucleosomes de novo, we
      generated nucleosome-depleted (ND) paternal pronuclei by depleting maternal
      histone H3.3 or its chaperone HIRA in mouse zygotes. We found that the ND
      pronucleus forms a nuclear envelope devoid of nuclear pore complexes (NPCs). Loss
      of NPCs is accompanied by defective localization of ELYS, a nucleoporin essential
      for NPC assembly, to the nuclear rim. Interestingly, tethering ELYS to the
      nuclear rim of the ND nucleus rescues NPC assembly. Our study thus demonstrates
      that nucleosome assembly is a prerequisite for NPC assembly during paternal
      pronuclear formation. 

PMID- 24908397
TI  - Structure-guided simulations illuminate the mechanism of ATP transport through
      VDAC1.
AB  - The voltage-dependent anion channel (VDAC) mediates the flow of metabolites and
      ions across the outer mitochondrial membrane of all eukaryotic cells. The open
      channel passes millions of ATP molecules per second, whereas the closed state
      exhibits no detectable ATP flux. High-resolution structures of VDAC1 revealed a
      19-stranded beta-barrel with an alpha-helix partially occupying the central pore.
      To understand ATP permeation through VDAC, we solved the crystal structure of
      mouse VDAC1 (mVDAC1) in the presence of ATP, revealing a low-affinity binding
      site. Guided by these coordinates, we initiated hundreds of molecular dynamics
      simulations to construct a Markov state model of ATP permeation. These
      simulations indicate that ATP flows through VDAC through multiple pathways, in
      agreement with our structural data and experimentally determined physiological
      rates. 

PMID- 24908399
TI  - Physiological response to etho-ecological stressors in male Alpine chamois:
      timescale matters!
AB  - From a life history perspective, glucocorticoids secreted by the neuroendocrine
      system, integrating different sources of stress through an adaptive feedback
      mechanism, may have important consequences on individual fitness. Although stress
      responses have been the object of several investigations, few studies have
      explored the role of proximate mechanisms responsible for the potential trade
      offs between physiological stress and life history traits integrating social and
      environmental stressors. In 2011 and 2012, we collected data on faecal cortisol
      metabolites (FCM) in a marked male population of Alpine chamois, within the Gran
      Paradiso National Park (Italy). Using a model selection approach we analysed the
      effect of potential etho-ecological stressors such as age, social status
      (territorial vs. non-territorial males), minimum temperature, snow depth and
      precipitation on FCM variation. To correctly interpret environmentally and
      socially induced stress responses, we conducted model selections over multiple
      temporal scales defined a priori: year, cold months, spring, warm months, mating
      season. Over the year, FCM levels showed a negative relationship with minimum
      temperature, but altogether, climatic stressors had negligible effects on
      glucocorticoid secretion, possibly owing to good adaptations of chamois to severe
      weather conditions. Age was negatively related to FCM during the rut, possibly
      due to greater experience of older males in agonistic contests. Social status was
      an important determinant of FCM excretion: while both the 'stress of
      subordination' and the 'stress of domination' hypotheses received some support in
      spring and during the mating season, respectively, previous data suggest that
      only the latter may have detrimental fitness consequences on male chamois. 

PMID- 24908398
TI  - Therapeutic effect and mechanism of electroacupuncture at Zusanli on plasticity
      of interstitial cells of Cajal: a study of rat ileum.
AB  - BACKGROUND: Electroacupuncture (EA) is one of the techniques of acupuncture and
      is believed to be an effective alternative and complementary treatment in many
      disorders. The aims of this study were to investigate the effects and mechanisms
      of EA at acupoint Zusanli (ST36) on the plasticity of interstitial cells of Cajal
      (ICCs) in partial bowel obstruction. METHODS: A Sprague Dawley rat model of
      partial bowel obstruction was established and EA was conducted at Zusanli (ST36)
      and Yinglingquan (SP9) in test and control groups, respectively. Experiments were
      performed to study the effects and mechanisms of EA at Zusanli on intestinal
      myoelectric activity, distribution and alteration of ICCs, expression of
      inflammatory mediators, and c-Kit expression. RESULTS: 1) EA at Zusanli somewhat
      improved slow wave amplitude and frequency in the partial obstruction rats. 2) EA
      at Zusanli significantly stimulated the recovery of ICC networks and numbers. 3)
      the pro-inflammatory mediator TNF-alpha and NO activity were significantly
      reduced after EA at Zusanli, However, no significant changes were observed in the
      anti-inflammatory mediator IL-10 activity. 4) EA at Zusanli re-expressed c-Kit
      protein. However, EA at the control acupoint, SP9, significantly improved slow
      wave frequency and amplitude, but had no effect on ICC or inflammatory mediators.
      CONCLUSIONS: We concluded that EA at Zusanli might have a therapeutic effect on
      ICC plasticity, and that this effect might be mediated via a decrease in pro
      inflammatory mediators and through the c-Kit signaling pathway, but that the
      relationship between EA at different acupoints and myoelectric activity needs
      further study.

PMID- 24908400
TI  - Sensing of Zn2+ ion by N-furfurylsalicylaldimine based on CHEF process.
AB  - The recognition ability of N-Furfurylsalicylaldimine (HL) toward various cations
      (Pb(2+), Hg(2+), Ba(2+), Cd(2+), Ag(+), Zn(2+), Cu(2+), Ni(2+), Co(2+), K(+),
      Sr(2+), and Na(+)) has been studied by UV-Vis and fluorescence spectroscopy. The
      compound showed highly selective fluorescence signaling behaviour for Zn(2+) ions
      in methanol-water medium based on CHEF process and is capable of distinguishing
      Zn(2+) from Cd(2+) ion. From single crystal X-ray analysis it is revealed that a
      Zn(2+) ion binds two ligand molecules through imine nitrogen and phenolate oxygen
      atom. 

PMID- 24908401
TI  - Cetuximab in refractory squamous cell carcinoma of the anal canal.

PMID- 24908402
TI  - Iodide mumps after trans-arterial chemoembolization procedure for treatment of
      hepatocellular carcinoma: a case report.

PMID- 24908403
TI  - Pericellular matrix plays an active role in retention and cellular uptake of
      large-sized nanoparticles.
AB  - As the outmost coating of cells, the pericellular matrix (PCM) involved in
      various cellular functions has been exploited previously to be able to accumulate
      120 nm Au nanoparticles (NPs), adjust their diffusion coefficient similar to that
      of membrane receptors, and enhance their uptake efficiency. In this study, the
      interactions between PCM and NPs with different sizes and materials were
      systematically investigated. We found that PCM can selectively enhance the
      retention and cellular uptake of NPs with diameters from 50 to 180 nm, but has no
      enhancement effect for 20 nm NPs. Identical behaviors of PCM was observed for
      both Au NPs and polystyrene NPs, indicating that this unique phenomenon is more
      related to the dimensions of the NPs. The study of single-particle tracking of 50
      180 nm NPs on the surface of thick PCM cells revealed that PCM actively adjusts
      the diffusion coefficient of NPs to ~0.1 MUm(2)/s regardless of their sizes. By
      blocking the receptor-mediated endocytosis (RME) pathway with four different
      inhibitors, this active role of PCM can be effectively suppressed, further
      confirming that the trapping and retention of NPs by PCM is an inherent
      biological function. These findings provided new insights for better
      understanding of the RME pathway and may have promising NP-based applications for
      controlled drug delivery and therapy in biomedicine.

PMID- 24908404
TI  - Optimization of capillary isotachophoretic method for determination of major
      macroelements in blue honeysuckle berries (Lonicera caerulea L.) and related
      products.
AB  - A reliable and repeatable isotachophoretic method for the simultaneous
      determination of K(+), Na(+), Ca(2+), Mg(2+), and ammonium in berries of
      different blue honeysuckle cultivars was developed. The usefulness of the complex
      forming equilibria in determining the cations mentioned above was studied. The
      addition of 7.5 mM 18-crown-6 and 2 mM alpha-hydroxyisobutyric acid to sulfuric
      acid enhanced the separation capacity of the leading electrolyte. The terminating
      electrolyte of 10 mM TRIS buffered to pH 4.30 was chosen as most appropriate for
      these studies. An ultrasound-assisted procedure for the extraction of
      macroelements from dried fruit of Lonicera caerulea L. was investigated using
      response surface methodology. The Box-Behnken experimental design showed the
      optimal extraction conditions as follows: temperature of 36  degrees C,
      extraction time of 42.3 min and solid-to-liquid ratio of 1:800 v/w. Detection
      limits for the method ranged from 0.030 to 0.097 mg/l with precision expressed by
      RSD ranging from 1.4 % for Mg to 4.4 % for Na. The results showed that blue
      honeysuckle berries are a good source of potassium, from 199 to 402 mg/100 g FW,
      especially 'Zielona' and 'Zojka' cultivars. The average content of other analytes
      in these berries was 5.2 mg Na, 24.8 mg Ca, 7.5 mg Mg and 52.0 mg ammonium per
      100 g FW. The berry products contained lower amounts of minerals especially Mg
      and K. However, a glass of freshly squeezed juice can provide almost 20 % of the
      RDI of potassium. The results obtained using both the developed isotachophoretic
      method and ion chromatographic procedure did not differ significantly.

PMID- 24908405
TI  - Zinc oxide nanoparticles based microfluidic immunosensor applied in congenital
      hypothyroidism screening.
AB  - In this article, we present an innovative approach for congenital hypothyroidism
      (CHT) screening. This pathology is the most common preventable cause of mental
      retardation, affecting newborns around the world. Its consequences could be
      avoided with an early diagnosis through the thyrotropin (TSH) level measurement.
      To accomplish the determination of TSH, synthesized zinc oxide (ZnO) nanobeads
      (NBs) covered by chitosan (CH), ZnO-CH NBs, were covalently attached to the
      central channel of the designed microfluidic device. These beads were employed as
      platform for anti-TSH monoclonal antibody immobilization to specifically
      recognize and capture TSH in neonatal samples without any special pretreatment.
      Afterwards, the amount of this trapped hormone was quantified by horseradish
      peroxidase (HRP)-conjugated anti-TSH antibody. HRP reacted with its enzymatic
      substrate in a redox process, which resulted in the appearance of a current whose
      magnitude was directly proportional to the level of TSH in the neonatal sample.
      The structure and morphology of synthesized ZnO-CH NBs were characterized by
      scanning electron microscopy (SEM) and X-ray diffraction (XRD). The calculated
      detection limits for electrochemical detection and the enzyme-linked
      immunosorbent assay procedure were 0.00087 MUUI mL(-1) and 0.015 MUUI mL(-1),
      respectively, and the within- and between-assay coefficients of variation were
      below 6.31% for the proposed method. According to the cut-off value for TSH
      neonatal screening, a reasonably good limit of detection was achieved. These
      above-mentioned features make the system advantageous for routine clinical
      analysis adaptation.

PMID- 24908407
TI  - Factors affecting the formation of the radiation pre-peak at the operation of a
      Grimm-type source in pulsed DC mode.
AB  - The plasma emission pre-peaks of many atomic and ionic spectral lines of Cu and
      Ar were systematically investigated in a Grimm-type pulsed glow discharge (PGD).
      To register the pre-peaks with sufficient time resolution, a monochromator with
      photomultiplier detection was used. When the applied power exceeded a specific
      threshold, pre-peaks were found in all spectral lines investigated, and it was
      revealed that the electrical pre-peak was the cause of the atomic emission pre
      peak. The form and intensity of the pre-peak radiation were, however, found to be
      different for different atomic emission lines. The excitation energy of the upper
      energy level of the atomic line transition, and factors related to recombination
      and self-absorption, were found to affect the emission pre-peak. Pre-peaks
      observed when using pulsed DC and pulsed radio-frequency power were compared.
      This investigation provides insight into best practice when selecting spectral
      lines most suitable for analytical spectrometry using PGD. 

PMID- 24908406
TI  - Statistical filtering in fluorescence microscopy and fluorescence correlation
      spectroscopy.
AB  - We review the principles and applications of statistical filtering in
      multichannel fluorescence microscopy. This alternative approach to separation of
      signals from individual fluorophore populations has many important advantages,
      especially when spectral and/or temporal overlap, or the complicated nature of
      those signals, makes their discrimination or sorting impossible by means of
      hardware. This situation is typically encountered for biological samples. This
      review of well established statistical filtering techniques and of emerging, very
      promising new methods of analysis reveals remarkable progress in bioanalytical
      applications of fluorescence microscopy. 

PMID- 24908408
TI  - Metal-nanoparticle-involved chemiluminescence and its applications in bioassays.
AB  - Chemiluminescence-based bioassays have become increasingly important in clinical,
      pharmaceutical, environmental, and food safety fields owing to their high
      sensitivity, wide linear range, and simple instrumentation. During the past
      decade, it has been found that metal nanoparticles can initiate various liquid
      phase chemiluminescence reactions as catalysts, reductants, energy acceptors, and
      nanosized reaction platforms owing to their unique optical, catalytic, and
      surface properties and chemical reactivity, which are very important for
      chemiluminescence bioassays based on metal nanoparticles as nanoprobes or a
      nanointerface. In this article, we summarize recent progress in metal
      nanoparticle-initiated liquid-phase chemiluminescence, including reaction
      systems, mechanisms, and their applications in chemiluminescence-based bioassays,
      especially for immunoassays, DNA assays, aptamer-based assays, high-performance
      liquid chromatography or capillary electrophoresis analysis, and flow injection
      analysis. 

PMID- 24908409
TI  - Raman spectroscopy applied to the horizontal methods ISO 6579:2002 to identify
      Salmonella spp. in the food industry.
AB  - Food safety is a major concern for suppliers in the food chain to ensure the
      safety of their products. The identification procedure requested by norms is
      tedious, and it often requires systematic controls and qualified staff to perform
      the necessary analyses. Raman spectroscopy offers new opportunities to rapidly
      and efficiently ascertain the presence of pathogens in samples. Nevertheless,
      this technique requires a standardized procedure to be applied in the industrial
      context. Our study shows that the variability between spectral fingerprints is
      related to the physiological state of the microbial species and the growth phase
      of the bacteria plays a crucial role in its identification by Raman spectroscopy.
      To improve the discrimination between closely related bacterial species, a
      procedure based on the selection of bacterial spectra in the exponential growth
      phase was proposed. Different ways to introduce Raman spectroscopy in the ISO
      6579:2002 standards are also proposed from the entire process to a shorter
      protocol. In the latter case, the identification of bacterial colonies after the
      selective enrichment step was proposed with the advantages of this path in terms
      of simplicity and rapidity (analysis time is reduced up to 50 h from the 100 h
      required by the standard). The protocol validated using six food categories from
      industrial partners have presented a good correlation by confirmation with other
      laboratory classical methods. In the future, this procedure could be introduced
      to the control system of the food production chain with a reliable database for
      various microorganisms encountered in this field.

PMID- 24908410
TI  - Quality fluctuation detection of an herbal injection based on biological
      fingerprint combined with chemical fingerprint.
AB  - Herbal injection is one of the most important preparations of traditional Chinese
      medicine. More than 130 types of herbal injections are used clinically for 400
      million patients annually with total sales of over four billion US dollars per
      year. However, the current quality control (QC) methods relying mainly on
      chemical fingerprints (CF) can hardly ensure quality and safety of the herbal
      injections with complex chemical composition and have resulted in an increase in
      serious adverse drug reactions. In this study, a comprehensive approach for the
      QC of a controversial herbal injection Shuang-Huang-Lian lyophilized powder (SHL)
      was established based on the quality fluctuation detection by a combination of CF
      and biological fingerprint (BF). High-performance liquid chromatography and the
      impedance-based xCELLigence system were applied to establish the CF and BF,
      respectively. In addition, multivariate analysis was performed to evaluate the
      discriminant ability of the two methods. The results showed that being subjected
      to environmental influence like oxygen/air, high temperature, and extreme
      illumination could lead to quality fluctuation of SHL. The combination of
      chemical and biological fingerprint method is a more powerful tool for the QC of
      SHL because it can clearly discriminate different groups of abnormal samples.
      This method can be used for the detection of quality fluctuation of SHL and can
      provide reference for the quality control of other herbal injections. 

PMID- 24908411
TI  - Analytical approaches for the determination of PCB metabolites in blood: a
      review.
AB  - Polychlorinated biphenyls (PCBs) are among the most ubiquitous pollutants in the
      environment, and their metabolism leads to the formation of hydroxylated PCBs (OH
      PCBs) and methyl sulfone PCBs (MeSO2-PCBs). These metabolites are generally more
      hydrophilic than the parent compound, and therefore are more easily eliminated
      from the body. However, some congeners have been shown to be strongly retained in
      human blood, binding to transthyretin with an affinity that is, in general,
      greater than that of the natural ligand thyroxin itself, which could result in
      toxicological effects, particularly on the thyroid system. Currently available
      analytical methods require, in general, extensive sample preparation, which
      includes a series of time-consuming and low-throughput liquid-liquid and back
      extractions, evaporations, several cleanup steps, and in some cases,
      derivatization prior to analysis by gas chromatography (GC) or liquid
      chromatography (LC) coupled with mass spectrometry (MS). Recent developments in
      the use of LC coupled with tandem MS (MS/MS) have brought some improvements in
      terms of sample preparation for the determination of PCB metabolites in blood,
      although there are still possibilities for continued development. The selected
      literature has evidenced few studies of LC-MS/MS-based methods, a lack of
      analytical standards, nonassessment of lower-chlorinated OH-PCBs, and scarce
      attention to MeSO2-PCBs in blood. This review aims to evaluate critically the
      currently available analytical methods for determination of OH-PCBs and MeSO2
      PCBs in blood. 

PMID- 24908412
TI  - Exploiting in vitro and in vivo bioluminescence for the implementation of the
      three Rs principle (replacement, reduction, and refinement) in drug discovery.
AB  - Bioluminescence-based analytical tools are suitable for high-throughput and high
      content screening assays, finding widespread application in several fields
      related to the drug discovery process. Cell-based bioluminescence assays, because
      of their peculiar advantages of predictability, possibility of automation,
      multiplexing, and miniaturization, seem the most appealing tool for the high
      demands of the early stages of drug screening. Reporter gene technology and the
      bioluminescence resonance energy transfer principle are widely used, and receptor
      binding studies of new agonists/antagonists for a variety of human receptors
      expressed in different cell lines can be performed. Moreover, bioluminescence can
      be used for in vitro and in vivo real-time monitoring of pathophysiological
      processes within living cells and small animals. New luciferases and substrates
      have recently arrived on the market, further expanding the spectrum of
      applications. A new generation of probes are also emerging that promise to
      revolutionize the preclinical imaging market. This formidable toolbox is
      demonstrated to facilitate the implementation of the three Rs principle in the
      early drug discovery process, in compliance with ethical and responsible research
      to reduce cost and improve the reliability and predictability of results. 

PMID- 24908413
TI  - Calibration strategies for the determination of stable carbon absolute isotope
      ratios in a glycine candidate reference material by elemental analyser-isotope
      ratio mass spectrometry.
AB  - We report a methodology for the determination of the stable carbon absolute
      isotope ratio of a glycine candidate reference material with natural carbon
      isotopic composition using EA-IRMS. For the first time, stable carbon absolute
      isotope ratios have been reported using continuous flow rather than dual inlet
      isotope ratio mass spectrometry. Also for the first time, a calibration strategy
      based on the use of synthetic mixtures gravimetrically prepared from well
      characterised, highly (13)C-enriched and (13)C-depleted glycines was developed
      for EA-IRMS calibration and generation of absolute carbon isotope ratio values
      traceable to the SI through calibration standards of known purity. A second
      calibration strategy based on converting the more typically determined delta
      values on the Vienna PeeDee Belemnite (VPDB) scale using literature values for
      the absolute carbon isotope ratio of VPDB itself was used for comparison. Both
      calibration approaches provided results consistent with those previously reported
      for the same natural glycine using MC-ICP-MS; absolute carbon ratios of 10,649 *
      10(-6) with an expanded uncertainty (k = 2) of 24 * 10(-6) and 10,646 * 10(-6)
      with an expanded uncertainty (k = 2) of 88 * 10(-6) were obtained, respectively.
      The absolute carbon isotope ratio of the VPDB standard was found to be 11,115 *
      10(-6) with an expanded uncertainty (k = 2) of 27 * 10(-6), which is in excellent
      agreement with previously published values. 

PMID- 24908414
TI  - Aberrant promoter methylation of p15 (INK4b) and p16 (INK4a) genes may contribute
      to the pathogenesis of multiple myeloma: a meta-analysis.
AB  - We carried out the current meta-analysis aiming to comprehensively assess the
      potential role of p15 (INK4b) and p16 (INK4a) aberrant promoter methylation in
      the pathogenesis of multiple myeloma (MM). The MEDLINE (1966 ~ 2013), Cochrane
      Library (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of
      Science (1945 ~ 2013), and Chinese Biomedical (CBM) (1982 ~ 2013) databases were
      searched without language restrictions. Meta-analyses were conducted using Stata
      software (Version 12.0, Stata Corporation, College Station, TX, USA). Odds ratios
      (ORs) and their 95 % confidence intervals (95 %CIs) were calculated. Thirteen
      clinical case-control studies, which enrolled a total of 465 MM patients and 180
      healthy subjects, were included in the meta-analysis. The results of our meta
      analysis demonstrated that the frequencies of p15 (INK4b) and p16 (INK4a)
      promoter methylation in cancer samples were significantly higher than in normal
      samples (p15 (INK4b) : OR = 6.26, 95 %CI = 3.87 ~ 10.12, P < 0.001; p16 (INK4a) :
      OR = 2.26, 95 %CI = 1.22 ~ 4.20, P < 0.001). Ethnicity-stratified analysis showed
      that the aberrant methylation of p15 (INK4b) was significantly related with the
      risk of MM among both Caucasians and Asians (all P < 0.05). Furthermore, our
      results also illustrated a strong positive correlation between p16 (INK4a)
      promoter methylation and the pathogenesis of MM among Asians (OR = 5.17, 95 %CI =
      3.45 ~ 7.74, P < 0.001), but not among Caucasians (P > 0.05). The current meta
      analysis confirms and reinforces existing findings that p15 (INK4b) and p16
      (INK4a) promoter methylation may be closely implicated in the pathogenesis of MM.

PMID- 24908415
TI  - Prognostic significance of VEGFR1/Flt-1 immunoexpression in colorectal carcinoma.
AB  - Colorectal carcinoma (CRC) is a major cause of morbidity and mortality. Vascular
      endothelial growth factor 1/Fms-like tyrosine kinase 1 (VEGFR1/Flt-1) regulates
      monocyte migration, recruits endothelial cell progenitors, increases the adhesive
      properties of natural killer cells and induces of growth factors. Flt-1 is
      expressed on tumour cells and has been implicated in tumour growth and
      progression. The objective of this study is to address the relation of Flt-1
      expression to tumour prognostication. Paraffin blocks from 143 primary CRC and 48
      regional nodal metastases were retrieved from the archives of the Department of
      Pathology at King Abdulaziz University. Tissue microarrays were designed and
      constructed. Immunohistochemistry for Flt-1 was performed. Staining intensity and
      extent of staining were assessed and combined. Results were dichotomised as low
      expression and high expression. Flt-1 was overexpressed in primary tumours and
      nodal metastasis (p < 0.001 and 0.001) with no difference between primary and
      nodal metastasis (p = 0.690). Flt-1 immunoexpression was not associated with the
      clinicopathological parameters. Flt-1 overexpression was an independent predictor
      of positive margin status, positive lymphovascular invasion and local disease
      recurrence (p < 0.001, p < 0.001 and p = 0.003, respectively). Flt-1 was not
      associated with survival (log-rank = 0.003, p = 0.959). Flt-1 was overexpressed
      in primary CRC and their nodal metastases. Flt-1 expression was an independent
      predictor of margin status, lymphovascular invasion and local disease recurrence.
      Therefore, expression profiling of Flt-1 seems to have a prognostic potential in
      CRC. However, to elucidate the association of overexpression of Flt-1 with tumour
      characteristics and prognostication, more in vivo and in vitro molecular
      investigations are recommended.

PMID- 24908416
TI  - [Ischemic stroke secondary to spontaneous arterial dissection of the internal
      carotid artery: a rare postpartum complication].
AB  - We report a case of ischemic stroke caused by internal carotid artery dissection
      in a 35-year-old woman in postpartum following spontaneous labor and vaginal
      delivery. Ischemic stroke due to arterial dissection requires rapid diagnosis and
      anticoagulation.

PMID- 24908417
TI  - [Denervation of the renal arteries: an old story?].

PMID- 24908418
TI  - [Idiopathic intracranial hypertension and factor V Leiden mutation].
AB  - Activated proteinC resistance is a frequent prothrombotic abnormality. In most
      cases it is due to factorV Leiden mutation by nucleotide G1691A substitution.
      This recently described thrombophilic defect of activated proteinC resistance has
      been postulated to be implicated in the pathogenesis of idiopathic intracranial
      hypertension (IIH). We report a case of factorV Leiden mutation in association
      with IIH and their likely link and implication in the management of IIH.

PMID- 24908419
TI  - [Compression and venous leg ulcer: observational study in general medicine].
AB  - INTRODUCTION: Multi-component compression, inelastic, short stretched or coated
      strips bandages, and class 4 stockings have been recommended since 2010 by the
      French Superior Health Authority as first- and second-line treatment for venous
      leg ulcers. OBJECTIVES: Assess the prescribing habits and knowledge of general
      practitioners about compression therapy and determine factors predictive of
      prescriptions consistent with recommendations. METHODS: Evaluation study of
      professional practices conducted during a six-week period. A questionnaire was
      sent to 210 general practitioners asking them to report their prescribing
      practices and the last prescription written for a patient with venous ulcers.
      RESULTS: The response rate was 36.2% (76 responses). For the last patient seen,
      long stretched bands were prescribed by 50.8% of responders, stockings by 40% and
      multi-component compression by 7.7%. Stockings were class 2 for 87.7% of the
      prescriptions. Knowledge of short stretched bands and multi-component compression
      was reported by 45.8% and 38.9% of general practitioners respectively. Guidelines
      were followed by 10.8% of the physicians. No factor related to the general
      practitioner (age, sex, modalities of exercise, experience and education), to the
      patients (age, sex, under-nutrition, autonomy) or to the leg ulcer (size,
      exudates, course, complexity of care), was associated with compliance or not with
      the guidelines. General practitioner training enabled a non-significant
      improvement of prescriptions (14.3% vs 4%, P=0.24). CONCLUSION: Compliance with
      the guidelines for compression therapy is insufficient in general medicine.
      Better training and knowledge of modalities for compression therapy could be
      useful to improve prescription practices and encourage use of multi-component
      compression and short stretched bandages, known to be more effective and better
      tolerated.

PMID- 24908420
TI  - Corneal collagen cross-linking in a late-onset graft infectious ulcer: a case
      report.
AB  - INTRODUCTION: Infectious keratitis following penetrating keratoplasty is a common
      postoperative complication. Intensive topical and systemic treatments do not
      always prevent the risk of graft failure. In this report we demonstrate the
      beneficial anti-microbial effect of corneal collagen cross-linking in a late
      onset, sight-threatening, corneal graft ulcer. CASE PRESENTATION: A 57-year old
      Caucasian man underwent penetrating keratoplasty in his left eye, due to corneal
      bullosa after cataract extraction surgery. Twelve months after the penetrating
      keratoplasty, he visited our emergency service complaining of burning and foreign
      body sensation in his operated eye. Slit-lamp examination revealed a central,
      round-shaped ulcer of the graft. Due to poor response to the intensive topical
      antibiotic therapy, corneal collagen cross-linking was applied 3 days after
      admission, in an attempt to control the infection. Cultures indicated the
      predominance of methicillin-resistant Staphylococcus aureus infection. Five days
      after corneal collagen cross-linking treatment, the epithelium was completely re
      epithelized, while the transparency of the transplanted cornea was gradually
      restored within the 12-month follow-up period. No relapses occurred. CONCLUSION:
      Corneal collagen cross-linking seems to be a safe and effective therapeutic
      alternative in resistant cases of infectious keratitis following penetrating
      keratoplasty.

PMID- 24908421
TI  - Long-term outcome of non-surgical root canal treatment: a retrospective analysis.
AB  - This study investigated the long-term clinical outcome of root canal treatment.
      240 root-treated teeth (n = 61 patients) were initially classified on the basis
      of radiographic presence/absence of initial apical periodontitis (IAP) and
      clinical data. The final outcome measure was the periapical healing
      (healed/disease). The outcome at 6-9 months was correlated with the outcome at 10
      years following treatment. Prognostic factors for the periapical healing were
      assessed. Extraction data were recorded. Univariate and multivariate logistic
      regression analysis was used to identify risk indicators for apical periodontitis
      (AP) development. Chi-square analysis was performed to evaluate a possible
      relationship between the 6-9 months outcome and the final outcome related to IAP.
      Mean observation time was 14 +/- 3.7 years. Survival rate was 84.6% and healing
      rate was 79% (10-19 years). Predictors of outcome (p < .05) were considered
      statistically significant. Multivariate logistic regression analysis showed that
      initial pulpal and periapical status and the quality of root canal filling as
      assessed two-dimensionally were independent predictors of outcome. The 6-9 months
      evaluation appears to be an indicator for the final outcome of primary root canal
      treatment both in the presence and in the absence of IAP. An initial radiolucency
      associated with an unsatisfactory quality and extent of root canal filling
      significantly diminishes the possibility of achieving long-term radiographic
      success. For those with uncertain healing at 6-9 months (91%), clinicians should
      consider the high healing rate when estimating the prognosis and adjust the
      decision making accordingly.

PMID- 24908422
TI  - Purification and characterization of cellulase-free low molecular weight endo
      beta-1,4 xylanase from an alkalophilic Cellulosimicrobium cellulans CKMX1
      isolated from mushroom compost.
AB  - Alkalophilic Cellulosimicrobium cellulans CKMX1 isolated from mushroom compost is
      first report on actinomycetes that has the ability to produce thermostable
      cellulase-free xylanase, which is an important industrial enzyme used in the pulp
      and paper industry. Strain CKMX1 was characterized by metabolic fingerprinting,
      whole-cell fatty acids methyl ester analysis and 16Sr DNA and found to be C.
      cellulans CKMX1.The enzyme was purified by gel permeation and anion exchange
      chromatography and had a molecular mass of 29 kDa. Xylanase activity was optimum
      at pH 8.0 and 55  degrees C. The enzyme was somewhat thermostable, retaining 50 %
      of the original activity after incubation at 50  degrees C for 30 min. The
      xylanase had K m and V max values of 2.64 mg/ml and 2,000 umol/min/mg protein in
      oat spelt xylan, respectively. All metal ions except HgCl2, CoCl2 as well as
      CdCl2 were well tolerated and did not adversely affect xylanase activity. The
      deduced internal amino acid sequence of C. cellulans CKMX1 xylanase by matrix
      assisted laser desorption ionization-time of flight mass spectrometry resembled
      the sequence of beta-1,4-endoxylanase, which is a member of glycoside hydrolase
      family 11. Some of the novel characteristics that make this enzyme potentially
      effective in xylan biodegradation could be useful for pulp and paper biobleaching
      are discussed in this manuscript.

PMID- 24908423
TI  - Pisum sativum p68 DEAD-box protein is ATP-dependent RNA helicase and unique
      bipolar DNA helicase.
AB  - DEAD-box helicases play essential role in DNA and RNA metabolism such as
      replication, repair, recombination, transcription, translation, ribosome
      biogenesis and splicing which regulate plant growth and development. The presence
      of helicases in the stress-induced ORFs identified by cDNA microarray indicates
      that helicases might be playing an important role in stabilizing growth in plants
      under stress. p68 DEAD-box helicase has been identified and characterized from
      animal systems but the properties and functions of plant p68 are poorly
      understood. In this study, the identification, purification and characterization
      of recombinant p68 from Pisum sativum (Psp68) is presented. Psp68 possesses all
      the characteristic motifs like DEAD-box ATP-binding and helicase C terminal
      motifs and is structurally similar to human p68 homologue. Psp68 exhibits ATPase
      activity in the presence of both DNA and RNA and it binds to DNA as well as RNA.
      It contains the characteristic RNA helicase activity. Interestingly Psp68 also
      shows the unique DNA helicase activity, which is bipolar in nature (unwinds DNA
      in both the 5'-3' and 3'-5' directions). The Km values of Psp68 for ATPase are
      0.5126 and 0.9142 mM in the presence of DNA and RNA, respectively. The Km values
      of Psp68 are 1.6129 and 1.14 nM for DNA helicase and RNA helicase, respectively.
      The unique properties of Psp68 suggest that it could be a multifunctional protein
      involved in different aspect of DNA and RNA metabolism. This discovery should
      make an important contribution to better understanding of nucleic acids
      metabolism plants. 

PMID- 24908425
TI  - Impact of cellular microenvironment and mechanical perturbation on calcium
      signalling in meniscus fibrochondrocytes.
AB  - Mechanical signals regulate a multitude of cell functions and ultimately govern
      fibrous tissue growth, maintenance and repair. Such mechanotransduction processes
      often involve modulation of intracellular calcium concentration ([Ca2+]i).
      However, most studies interrogate these responses in cells in simplified culture
      systems, thereby removing potentially important inputs from the native
      extracellular microenvironment. The objective of this study was to test the
      hypothesis that the intracellular calcium response of meniscus fibrochondrocytes
      (MFCs) is dependent on both the microenvironmental context in which this
      perturbation is applied and on the tensile deformation. Using a custom micro
      mechanical tester mounted on a confocal microscope, intracellular calcium
      activity in MFCs in response to incremental tissue strains (0, 3, 6 and 9 %) was
      monitored in situ (i.e., in the native tissues) on MFC-seeded aligned scaffolds
      and MFC-seeded silicone membranes. The [Ca2+]i regulation by MFCs within the
      native meniscus tissue microenvironment was considerably different from [Ca2+]i
      regulation by MFCs on either aligned nanofibrous scaffolds or flat silicone
      membranes. Additionally, increasing levels of tensile deformation resulted in a
      greater number of responding cells, both in situ and in vitro, while having no
      effects on temporal characteristics of [Ca2+]i signalling. Collectively, these
      findings have significant implications for mechanobiology of load-bearing fibrous
      tissues and their responses to injury and degeneration. In addition, from a
      tissue engineering perspective, the findings establish cellular benchmarks for
      maturing engineered constructs, where native tissue-like calcium mechano
      regulation may be an important outcome parameter to achieve mechanical
      functionality comparable to native tissue. 

PMID- 24908424
TI  - Genomic classification of the RAS network identifies a personalized treatment
      strategy for lung cancer.
AB  - Better approaches are needed to evaluate a single patient's drug response at the
      genomic level. Targeted therapy for signaling pathways in cancer has met limited
      success in part due to the exceedingly interwoven nature of the pathways. In
      particular, the highly complex RAS network has been challenging to target.
      Effectively targeting the pathway requires development of techniques that measure
      global network activity to account for pathway complexity. For this purpose, we
      used a gene-expression-based biomarker for RAS network activity in non-small cell
      lung cancer (NSCLC) cells, and screened for drugs whose efficacy was
      significantly highly correlated to RAS network activity. Results identified EGFR
      and MEK co-inhibition as the most effective treatment for RAS-active NSCLC
      amongst a panel of over 360 compounds and fractions. RAS activity was identified
      in both RAS-mutant and wild-type lines, indicating broad characterization of RAS
      signaling inclusive of multiple mechanisms of RAS activity, and not solely based
      on mutation status. Mechanistic studies demonstrated that co-inhibition of EGFR
      and MEK induced apoptosis and blocked both EGFR-RAS-RAF-MEK-ERK and EGFR-PI3K-AKT
      RPS6 nodes simultaneously in RAS-active, but not RAS-inactive NSCLC. These
      results provide a comprehensive strategy to personalize treatment of NSCLC based
      on RAS network dysregulation and provide proof-of-concept of a genomic approach
      to classify and target complex signaling networks.

PMID- 24908426
TI  - A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a
      contaminated in vivo bone defect model.
AB  - Open fractures are at risk of serious infection and, if infected, require several
      surgical interventions and courses of systemic antibiotics. We investigated a new
      injectable formulation that simultaneously hardens in vivo to form a porous
      scaffold for bone repair and delivers antibiotics at high concentrations to the
      local site of infection. Duration of antimicrobial activity against
      Staphylococcus aureus was determined using the serial plate transfer test.
      Ultimate compressive strength and porosity of the material was measured with and
      without antibiotics. The material was evaluated in vivo in an ovine medial
      femoral condyle defect model contaminated with S. aureus. Sheep were sacrificed
      at either 2 or 13 weeks and the defect and surrounding bone assessed using micro
      computed tomography and histology. Antimicrobial activity in vitro persisted for
      19-21 days. Sheep with antibiotic-free material and bacteria became infected,
      while those with antibiotic-containing material and bacteria did not. Similarly,
      new bone growth was seen in uninoculated animals with plain polymer, and in those
      with antibiotic polymer with bacteria, but not in sheep with plain polymer and
      bacteria. The antibiotic-impregnated scaffolds were effective in preventing S.
      aureus infections whilst supporting bone growth and repair. If translated into
      clinical practice, this approach might reduce the need for systemic antibiotics. 

PMID- 24908427
TI  - Oral complaints and dental care of haematopoietic stem cell transplant patients:
      a qualitative survey of patients and their dentists.
AB  - PURPOSE: Little is known about the understanding of the oral and dental needs of
      haematopoietic stem cell transplant (HSCT) patients or about dentists' views and
      experiences regarding this patient group. This information is essential if we
      want to improve the standard of peri-HSCT dental care. The primary objective of
      this qualitative survey was to explore the following: (1) The understanding of
      dental care pre- and post-HSCT (2) The subjective oral complaints of HSCT
      patients both short- and long-term (3) The relationship of these oral complaints
      to the severity of oral mucositis during hospitalization The secondary objective
      was to explore the opinions of dentists regarding dental care before and after
      HSCT. PATIENTS AND METHODS: All adult patients who survived HSCT at the Radboud
      University Medical Centre between 2010 and 2011 (n = 101) received a
      questionnaire. During hospitalization, mucositis scores were recorded daily in
      the patient's chart. The patients' dentist (n = 88) was also sent a questionnaire
      after permission of the patient. RESULTS: Ninety-six out of 101 patients (95%)
      responded. The average period since HSCT was 19 months (range 8-31 months). The
      overall mean maximum mucositis score was 6.6 (sd = 3.3). Only eight patients
      reported not having visited a dentist pre-HSCT. The majority of the patients
      (59%) reported short-term oral complaints, and 28% reported long-term oral
      complaints. Fifty-two dentists responded (59%). Nine had not performed pre-HSCT
      screening and eight dentists reported screening their patients but could not
      complete the necessary treatments. Only 44 dentists succeeded in completing the
      required treatments. The most important advice of the dentist was to reinforce
      the importance of regular dental care. CONCLUSION: Most patients report short
      term and/or long-term oral complaints after HSCT. Most dentists stress the
      importance of regular dental care before and after HSCT but report not being
      familiar with the particular dental care needs of this patient group. The high
      response rate and the high rate of HSCT-related oral complaints emphasize the
      need of further research in this area.

PMID- 24908428
TI  - Marital status and optimism score among breast cancer survivors.
AB  - PURPOSE: There are an increasing number of breast cancer survivors, but their
      psychosocial and supportive care needs are not well-understood. Recent work has
      found marital status, social support, and optimism to be associated with quality
      of life, but little research has been conducted to understand how these factors
      relate to one another. METHODS: Survey data from 722 breast cancer survivors were
      analyzed to estimate the association between marital status and optimism score,
      as measured using the Life Orientation Test-Revised. Linear regression was used
      to estimate the relationship of marital status and optimism, controlling for
      potential confounding variables and assessing effect modification. RESULTS: The
      results showed that the association between marital status and optimism was
      modified by time since breast cancer diagnosis. Specifically, in those most
      recently diagnosed (within 5 years), married breast cancer survivors had a 1.50
      higher mean optimism score than unmarried survivors (95 % confidence interval
      (CI) 0.37, 2.62; p = 0.009). The difference in optimism score by marital status
      was not present more than 5 years from breast cancer diagnosis. CONCLUSIONS:
      Findings suggest that among breast cancer survivors within 5 years since
      diagnosis, those who are married have higher optimism scores than their unmarried
      counterparts; this association was not observed among longer-term breast cancer
      survivors. Future research should examine whether the difference in optimism
      score among this subgroup of breast cancer survivors is clinically relevant.

PMID- 24908429
TI  - Potential benefits of early nutritional intervention in adults with upper
      gastrointestinal cancer: a pilot randomised trial.
AB  - PURPOSE: This study aimed to test whether a very early nutrition intervention
      delivered over the telephone was feasible and could improve outcomes amongst
      patients with upper gastrointestinal cancer. METHODS: Participants with a
      histologically proven new diagnosis of primary oesophageal or stomach cancer and
      who were to undergo surgery and/or chemotherapy were randomised to receive either
      standard nutrition care (SC) or early and intensive nutrition intervention (NI)
      over the telephone/face-to-face. Participants were followed for 6 months. The
      primary outcome was quality of life (QoL), assessed using the European
      Organization for Research and Treatment of Cancer Global Quality of Life
      questionnaire C30 (EORTC QLQ-C30) and the European Quality of Life Instrument (EQ
      5D) tool; secondary outcomes were nutritional status and survival. RESULTS:
      Twenty-one participants were recruited (11 SC and 10 NI). At baseline, the
      prevalence of malnutrition was 90 %. Compared with SC, the NI group had a
      significantly higher EORTC global QoL score at the first mid-study follow-up
      (coefficient (95 % CI) 21.0 (12.1, 29.9) adjusted for baseline, p < 0.001) and at
      26 weeks (28.4 (21.3, 35.4) adjusted for baseline, p < 0.001). Nutritional risk
      score was lower (p < 0.001), and loss of body weight attenuated (p < 0.001) in
      the NI group compared with SC. Six deaths occurred during the study, five in the
      SC group and one in the NI group (p = 0.06). The mean time spent with a dietitian
      per contact was significantly less for the NI group compared with SC (16(3) vs
      40(6) min per dietetic contact, p < 0.001). CONCLUSIONS: This pilot study has
      shown the potential of a novel telephone-based early and intensive dietetic model
      of care for newly diagnosed upper gastrointestinal cancer patients.

PMID- 24908430
TI  - A polysaccharide from Grifola frondosa relieves insulin resistance of HepG2 cell
      by Akt-GSK-3 pathway.
AB  - Grifola frondosa is an important fungal research resource. However, there was
      little report about hyperglycemic activity of Grifola frondosa polysaccharide on
      insulin resistance in vitro. In this study, the hypoglycemic activity of a
      polysaccharide obtained from Grifola frondosa (GFP) on HepG2 cell and
      hpyerglycemic mechanism were investigated. The purity of the isolated
      polysaccharides was examined by HPLC. In this research, it was found that GFP
      enhanced the absorption of glucose of HepG2 cells in a dose dependent manner at
      24 h of 30 ugmL-1. GC-MS and FT-IR spectroscopy analysis results showed that
      glucose and galactose were the dominant monosaccharides in GFP and the major
      component of GFP was beta-pyranoside. Western-blotting results showed that the
      HepG2 cell model treated with GFP activated the insulin receptor protein (IRS) in
      the cell membrane and increased phosphorylated-AktSer473 expression, which had an
      inhibition of glycogen synthase kinase (GSK-3). The down-regulation of GSK-3
      stimulated synthesis of intracellular glycogen. The results above suggested that
      the GFP increased the metabolism of glucose and stimulated synthesis of
      intracellular glycogen through the Akt/GSK-3 pathway.

PMID- 24908431
TI  - Ubiquitination-mediated interaction among domains is responsible for inhibition
      of RNA endonuclease activity of mRNA cycling sequence binding protein from L.
      donovani (LdCSBP).
AB  - In nearly complete absence of transcriptional regulation, messenger RNA (mRNA)
      turnover mediated through specific cis-elements plays a predominant role in the
      control of differential gene expression for the disease causing trypanosomatid
      parasites. In these organisms, the periodic accumulation of S-phase messages
      during cell cycle is determined by the presence of one or more copies of a
      conserved CAUAGAAG octanucleotide motif in the untranslated regions of mRNAs. In
      our previous studies, a multi-domain cycling sequence binding protein LdCSBP from
      Leishmania donovani was characterized, which binds specifically to the octamer
      containing RNAs via its uniquely arranged CCCH-type Zn fingers and degrades them
      through its small MutS-related (Smr) endonuclease domain, indicative of its
      potential role in the turnover of the S-phase mRNAs. Interestingly, the protein
      is modified by the incorporation of a monoubiquitin residue, and the
      posttranslational modification inhibits its riboendonuclease activity. However,
      the mechanism of such inhibition was previously unknown. Here, we establish that
      the CCCH-type Zn finger domain is the site of ubiquitination in LdCSBP and the
      interaction of CUE domain of the protein with the ubiquitinated Zn finger domain
      is responsible for inhibition of its riboendonuclease activity. The findings
      elucidate an inhibitory mechanism of RNA cleavage through ubiquitination-mediated
      intramolecular interaction among domains of the enzyme. Furthermore, the
      riboendonuclease activity is inhibited by anti-leishmanial drug paromomycin
      suggesting that the regulation of RNA metabolism could be a target of the drug. 

PMID- 24908432
TI  - Description and molecular characterization of Haemoproteus macrovacuolatus n. sp.
      (Haemosporida, Haemoproteidae), a morphologically unique blood parasite of black
      bellied whistling duck (Dendrocygna autumnalis) from South America.
AB  - During a surveillance programme on avian influenza in wild birds in the east of
      Colombia, 42% of examined wild black-bellied whistling ducks (Dendrocygna
      autumnalis) were infected with undescribed Haemoproteus sp., which
      macrogametocytes possess one or several huge (2.5 MUm in largest diameter)
      conspicuous roundish vacuoles, a unique character of avian haemoproteids. This
      parasite is named Haemoproteus (Parahaemoproteus) macrovacuolatus and described
      here using data on the morphology of its gametocytes, host cells and sequences of
      the complete mitochondrial genome and cytochrome b fragments. Illustrations of
      blood stages of the new species and DNA sequence information are provided. The
      phylogenetic analysis identified a closely related lineage C033, reported in
      South Asian ducks belonging to Dendrocygna. We also found that all Haemoproteus
      lineages from Passeriformes conformed a monophyletic group. Whereas we cannot
      exclude that this pattern could be an artefact of the limited taxonomic sampling
      in non-passeriform birds, thus this finding is worthy of attention. This study
      adds to our knowledge of the phylogenetic relationships among species of avian
      haemoproteids and describes a new haemoparasite in a non-passerine host.

PMID- 24908433
TI  - Protective efficacy in chickens of recombinant plasmid pET32a(+)-ADF-3-1E of
      Eimeria acervulina.
AB  - This experiment was conducted to study the protective efficacy of recombinant
      plasmid pET32a(+)-ADF-3-1E in coccidian-infected breeding chickens. The 7-day-old
      chickens were randomly divided into five groups: a recombinant plasmid pET32a(+)
      ADF-3-1E group, a pET32a(+)-ADF group, a pET32a(+)-3-1E group, a control group,
      and an infection control group. The chickens were immunized intramuscularly with
      recombinant plasmid DNA in a dose of 200 MUg, respectively, and a booster
      vaccination was given at the same dosage 1 week later. The peripheral blood T
      lymphocyte proliferation, serum IgG antibody response, and levels of interleukin
      2 (IL-2) and interferon gamma (IFN-gamma) were detected, respectively. The
      chickens were inoculated with 4 * 10(6) Eimeria acervulina-sporulated oocysts
      (Baoding strain) on the seventh day after the last immunization to evaluate the
      protective efficiency of the recombinant plasmid DNA. The results showed that the
      lymphocyte proliferation, serum IgG antibody, and IL-2 and IFN-gamma levels in
      recombinant plasmid DNA group were significantly higher than those in control
      group (P < 0.01). The lymphocyte proliferation, serum IgG antibody, and IL-2 and
      IFN-gamma levels in pET32a(+)-ADF-3-1E group were significantly higher than those
      in pET32a(+)-3-1E group and pET32a(+)-ADF group, respectively (P < 0.05). It
      indicated that the pET32a(+)-ADF-3-1E could produce stronger immune responses.
      The relative body weight gain rate in pET32a(+)-ADF-3-1E group was 88.36 %, which
      was significantly higher than that in control group (P < 0.05) and infection
      control group (P < 0.01). The reductions of oocyst production and lesion scores
      in pET32a(+)-ADF-3-1E group were 67.88 and 67.13 %, respectively. The oocyst
      excretion and the lesion score of chickens in pET32a(+)-ADF-3-1E group were lower
      than those in infection control group, respectively. Anticoccidial index (ACI)
      value in group immunized with pET32a(+)-ADF-3-1E was 169.82. ACI value of 160-179
      was considered as effective. These results demonstrated that the pET32a(+)-ADF-3
      1E recombinant plasmid DNA could effectively improve the cellular responses and
      humoral immune responses of the chickens, and it might provide protection against
      coccidiosis in chickens.

PMID- 24908434
TI  - Characterization, mode of action, and efficacy of twelve silica-based acaricides
      against poultry red mite (Dermanyssus gallinae) in vitro.
AB  - Poultry red mite infestation still is an unsolved problem in poultry farms. Legal
      regulations, residue risks, and resistances limit chemical control of mites.
      Alternatives to chemical acaricides for control of poultry red mite are silica
      based products, which have as a main constituent silicon dioxide. The acaricidal
      effect is attributed to sorptive properties of the particles, which result in the
      mite's death by desiccation. In the present study, the acaricidal efficacy of 12
      products containing natural or synthetic silica, 9 in powder form, and 3 for
      liquid application was tested under laboratory conditions. Mite mortality was
      measured at several intervals and the mean lethal time (LT50) determined by
      Probit analysis after Abbott's correction. The LT50 values of the products
      significantly differed (Tukey's HSD p < 0.05). LT50 values of powdery
      formulations ranged from 5.1 to 18.7 h and overlapped with those of the fluid
      ones which ranged from 5.5 to 12.7 h. In order to explain the differences in
      efficacy of the tested silica products, further characterizations were carried
      out. X-ray fluorescence, specific surface, cation exchange capacity (CEC), and
      water absorption capacity (WAC) were measured. Furthermore, electron microscopy
      was conducted and different products compared. Silicon dioxide content (ranging
      from 65 to 89% for powders and 57 to 80% for fluids) had no significant impact on
      efficacy, while specific surface and CEC (2.4-23.2 mEq 100(-1) g(-1) for powders
      and 18-30.8 mEq 100(-1) g(-1)) were positively and WAC (1.3-4.4 wt% for powders
      and 3.3-4.8 wt% for fluids) negatively related to the acaricidal efficacy.
      Influence of these parameters on acaricidal efficacy was significant according to
      the results of a stepwise regression analysis (p < 0.01).

PMID- 24908435
TI  - Phase I dose escalation study of capecitabine and erlotinib concurrent with
      radiation in locally advanced pancreatic cancer.
AB  - PURPOSE: Pancreatic cancer is one of the leading causes of cancer-related deaths
      worldwide. The median survival of locally advanced nonoperable disease is
      approximately 9 months. 5-FU-based chemoradiotherapy has been the standard
      treatment. However, the survival benefit of this approach is modest. To improve
      the efficacy of 5-FU-based chemoradiation therapy, we evaluated the safety and
      feasibility of the combination of capecitabine and erlotinib with radiotherapy in
      this group of patients. EXPERIMENTAL DESIGN: A traditional "3 + 3" dose
      escalation design was adopted in the study. A total of four dose levels were
      designed. For safety purpose, a minus I dose level (-I) was also planned. The -I
      level consisted of capecitabine 600 mg/m2 and erlotinib 50 mg daily, and the
      remaining four dose levels were as follows: level I: capecitabine 600 mg/m2 bid
      (twice daily); level II: 700 mg/m2 bid; level III: 825 mg/m2 bid; and level IV:
      925 mg/m2 bid. Erlotinib was administered at 100 mg daily at all dose levels.
      Erlotinib and capceitabine were given continuously Monday through Friday
      concurrent with radiotherapy (50.4 Gy in 28 fractions). RESULTS: A total of 18
      patients were consented. Fifteen patients were enrolled and completed therapy. No
      dose-limiting toxicity was observed. The most frequent side effects were
      lymphopenia, nausea, vomiting, diarrhea, electrolyte imbalances, and skin rashes.
      The majority of the toxicities were grade 1 and 2. No objective response was
      observed. The median progression-free survival was 0.59 years (95 % CI 0.31-1.1),
      and the median overall survival was 1.1 years (95 % CI 0.62-1.59). CONCLUSIONS:
      The combination of capecitabine and erlotinib with radiotherapy in locally
      advanced pancreatic cancer is well tolerated and feasible at the dose level of
      capecitabine 925 mg/m2 bid and erlotinib 100 mg daily.

PMID- 24908437
TI  - Enhanced skin toxicity associated with the combination of clofarabine plus
      cytarabine for the treatment of acute leukemia.
AB  - PURPOSE: Skin toxicity is associated with a number of different chemotherapeutic
      agents used to treat acute leukemias. The term "toxic erythema of chemotherapy"
      (TEC) has been coined to describe a spectrum of skin findings, ranging from
      palmar-plantar erythrodysesthesia to erythema of major body folds, with
      erythroderma representing its most severe form. To clarify the types and
      frequencies of cutaneous reactions associated with clofarabine plus cytarabine
      chemotherapy and to compare these to those observed with clofarabine alone, we
      reviewed our institutional experience over a 5-year period. METHODS: We reviewed
      the medical records of 49 patients who were treated with either regimen for acute
      leukemia. To facilitate comparison of the cutaneous toxicities, only patients
      treated with clofarabine 40 mg/m(2) daily for 5 days (days 1-5) with or without
      cytarabine 1 g/m(2) daily for 5 days (days 2-6) were included. RESULTS: Ten
      patients were treated with clofarabine alone, and 40 patients received
      clofarabine plus cytarabine; one patient received both regimens. Treatment
      associated skin toxicity developed 3-9 days following the initiation of
      chemotherapy and was more common in the group receiving the two-drug combination
      as compared to those receiving clofarabine alone [22/40 (55%) vs. 1/10 (10%)
      respectively, p = 0.014]. The majority of chemotherapy-related cutaneous side
      effects represented TEC. CONCLUSIONS: Cutaneous toxicity was common and more
      frequent in the clofarabine plus cytarabine group when compared to patients
      treated with clofarabine alone. This finding is relevant for both clinicians and
      patients.

PMID- 24908436
TI  - Novel DNA methyltransferase-1 (DNMT1) depleting anticancer nucleosides, 4'-thio
      2'-deoxycytidine and 5-aza-4'-thio-2'-deoxycytidine.
AB  - PURPOSE: Currently approved DNA hypomethylating nucleosides elicit their effects
      in part by depleting DNA methyltransferase I (DNMT1). However, their low response
      rates and adverse effects continue to drive the discovery of newer DNMT1
      depleting agents. Herein, we identified two novel 2'-deoxycytidine (dCyd)
      analogs, 4'-thio-2'-deoxycytidine (T-dCyd) and 5-aza-4'-thio-2'-deoxycytidine
      (aza-T-dCyd) that potently deplete DNMT1 in both in vitro and in vivo models of
      cancer and concomitantly inhibit tumor growth. METHODS: DNMT1 protein levels in
      in vitro and in vivo cancer models were determined by Western blotting and
      antitumor efficacy was evaluated using xenografts. Effects on CpG methylation
      were evaluated using methylation-specific PCR. T-dCyd metabolism was evaluated
      using radiolabeled substrate. RESULTS: T-dCyd markedly depleted DNMT1 in CCRF-CEM
      and KG1a leukemia and NCI-H23 lung carcinoma cell lines, while it was ineffective
      in the HCT-116 colon or IGROV-1 ovarian tumor lines. On the other hand, aza-T
      dCyd potently depleted DNMT1 in all of these lines indicating that dCyd analogs
      with minor structural dissimilarities induce different DNMT1 turnover mechanisms.
      Although T-dCyd was deaminated to 4'-thio-2'-deoxyuridine, very little was
      converted to 4'-thio-thymidine nucleotides, suggesting that inhibition of
      thymidylate synthase would be minimal with 4'-thio dCyd analogs. Both T-dCyd and
      aza-T-dCyd also depleted DNMT1 in human tumor xenografts and markedly reduced in
      vivo tumor growth. Interestingly, the selectivity index of aza-T-dCyd was at
      least tenfold greater than that of decitabine. CONCLUSIONS: Collectively, these
      data show that 4'-thio modified dCyd analogs, such as T-dCyd or aza-T-dCyd, could
      be a new source of clinically effective DNMT1 depleting anticancer compounds with
      less toxicity.

PMID- 24908439
TI  - Automated image-based tracking and its application in ecology.
AB  - The behavior of individuals determines the strength and outcome of ecological
      interactions, which drive population, community, and ecosystem organization. Bio
      logging, such as telemetry and animal-borne imaging, provides essential
      individual viewpoints, tracks, and life histories, but requires capture of
      individuals and is often impractical to scale. Recent developments in automated
      image-based tracking offers opportunities to remotely quantify and understand
      individual behavior at scales and resolutions not previously possible, providing
      an essential supplement to other tracking methodologies in ecology. Automated
      image-based tracking should continue to advance the field of ecology by enabling
      better understanding of the linkages between individual and higher-level
      ecological processes, via high-throughput quantitative analysis of complex
      ecological patterns and processes across scales, including analysis of
      environmental drivers.

PMID- 24908438
TI  - Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate
      levels in Chinese children with acute lymphoblastic leukemia.
AB  - PURPOSE: To investigate the correlation between common genetic polymorphisms of
      folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), and
      methylenetetrahydrofolate reductase (MTHFR) and serum levels of methotrexate
      (MTX) in Chinese children with acute lymphoblastic leukemia (ALL). METHODS:
      Ninety-one children with ALL who received high-dose MTX were recruited. The
      polymorphisms FPGS (rs1544105 G>A), GGH (rs3758149 C>T), and MTHFR (rs1801133
      C>T) were genotyped through polymerase chain reaction-restriction fragment length
      polymorphism analysis. Serum MTX was measured by fluorescence polarization
      immunoassay. The association between targeted polymorphisms and MTX concentration
      to-dose (C/D) ratios was assessed, and between targeted polymorphisms and the
      percent of MTX above the therapeutic threshold (40 umol/L). RESULTS: The minor
      allele frequencies of rs1544105 G (34.1%), rs3758149 T (19.2%), and rs1801133 C
      (48.4%) observed in our population were significantly lower than those reported
      for European populations (64.2, 30.8, and 69.0%, respectively). The association
      between the GGH rs3758149 polymorphism and MTX C/D was gender-specific; in girls,
      the MTX C/D at 24 h of GGH rs3758149 CC carriers (12.09 MUmol/L per g/m(2)) was
      significantly lower than that of CT or TT carriers (16.80 MUmol/L per g/m(2)).
      The percent of serum MTX above the therapeutic threshold in GGH rs3758149 CC
      carriers (18.3%) was significantly lower than that of CT and TT carriers (38.7%).
      The MTX C/D ratios at 24 h and the percent of MTX >40 umol/L for the A-T-T (three
      variant alleles) haplotype were significantly higher than those for other
      haplotypes combined (P < 0.05). CONCLUSIONS: These data indicate that FPGS
      rs1544105, GGH rs3758149, and MTHFR rs1801133 polymorphisms contribute to the
      variability of MTX pharmacokinetics, and their genotyping may be useful to reduce
      toxicities associated with MTX therapy.

PMID- 24908440
TI  - Acute pancreatitis due to extracorporeal shock wave lithotripsy: a rare
      complication.
AB  - Extracorporeal shock wave lithotripsy (ESWL) is considered the treatment of
      choice for most renal and upper ureteral stones. Although extensive data have
      documented its safety, serious complications have been reported in 1% of
      patients, including acute pancreatitis, perirenal hematoma, urosepsis, venous
      thrombosis, biliary obstruction, bowel perforation, lung injury, and rupture of
      aortic aneurysms. Here, we report a 41-year-old woman who underwent ESWL for a
      calculus at the right renal pelvis and immediately developed acute pancreatitis
      after the procedure. Although the possibility of post-ESWL acute pancreatitisis
      extremely low, physicians must be aware of this complication in emergency
      departments.

PMID- 24908441
TI  - Back to underlying pathogenesis of pheochromocytoma, the way we treat and the way
      we think.

PMID- 24908442
TI  - HIV rapid testing in a Veterans Affairs hospital ED setting: a 5-year
      sustainability evaluation.
AB  - Routine HIV testing in primary care settings is now recommended in the United
      States. The US Department of Veterans Affairs (VA) has increased the number of
      patients tested for HIV, but overall HIV testing rates in VA remain low. A proven
      strategy for increasing such testing involves nurse-initiated HIV rapid testing
      (HIV RT). The purpose of this work was to use a mixed methodology approach to
      evaluate the 5-year sustainability of an intervention that implemented HIV RT in
      a VA emergency department setting in a large, urban VA medical center to reduce
      missed diagnostic and treatment opportunities in this vulnerable patient
      population. In-person semistructured interviews were conducted with providers and
      stakeholders. Interview notes were qualitatively coded for emerging themes.
      Quarterly testing rates were evaluated for a 5-year time span starting from the
      launch in July 2008. Findings indicate that HIV RT was sustained by the
      enthusiasm of 2 clinical champions who oversaw the registered nurses responsible
      for conducting the testing. The departure of the clinical champions was
      correlated with a substantial drop-off in testing. Findings also indicate
      potential strategies for improving sustainability including engaging senior
      leadership in the project, engaging line staff in the implementation planning
      from the start to increase ownership over the innovation, incorporating
      information into initial training explaining the importance of the innovation to
      quality patient care, providing ongoing training to maintain skills, and
      providing routine progress reports to staff to demonstrate the ongoing impact of
      their efforts. 

PMID- 24908443
TI  - Cysticercotic encephalitis: a life threatening form of neurocysicercosis.
AB  - Neurocysticercosis is the most frequent neuroparasitosis and is caused by Taenia
      solium larvae (cysticerci). Its most common presenting feature is seizure,
      although it may present as headache,focal deficits, hydrocephalous, or as
      features of raised intracranial pressure. We herein report a case of 40-year-old
      male who presented with features of acute encephalitis and raised intracranial
      pressure with magnetic resonance imaging suggestive of multiple neurocysticerci
      with diffuse cerebral edema. A diagnosis of cysticercotic encephalitis was made,
      which is a syndrome of encephalitis with clinical and radiologic evidences of
      diffuse cerebral edema caused by parenchymal cysticercosis. It is important for
      the clinicians to be aware of this medical emergency requiring urgent attention
      as delay may lead to fatal outcome.

PMID- 24908444
TI  - The electric Kool-Aid NBOMe test: LC-TOF/MS confirmed 2C-C-NBOMe (25C)
      intoxication at Burning Man.
AB  - Designer drugs are constantly evolving, with the NBOMe derivatives of the 2C
      class of phenethylamines recently emerging in the US market. Cases of 2C-I-NBOMe
      toxicity have recently been reported in the literature. No reports to date
      describe the clinical effects 2C-C-NBOMe toxicity.

PMID- 24908445
TI  - An observational case series of dabigatran and rivaroxaban exposures reported to
      a poison control system.
AB  - OBJECTIVE: Characterize clinical presentations and outcomes of dabigatran and
      rivaroxaban exposures reported to a poison control system. METHODS: Data for
      cases of dabigatran and rivaroxaban exposures called into the California Poison
      Control System from January 2011 to July 2013 were collected. Data collected
      included patient demographics, type of exposure, medication, dosage, vital signs,
      laboratory values, interventions, outcomes, and disposition. Exclusion criteria
      included confirmed nonexposures or miscoded cases. RESULTS: A total of 56 cases
      were identified, with 7 excluded, leaving 37 dabigatran and 12 rivaroxaban cases.
      Children age 12 years or less accounted for 5 dabigatran and 2 rivaroxaban cases.
      Bleeding was reported in 15 dabigatran cases. There were 4 cases of acute self
      harm overdose with dabigatran ranging from 1800 to 3900 mg. Mild bleeding was
      reported in only one of these overdose cases. There were 2 fatal hemorrhages in
      dabigatran cases, both in chronic therapeutic dosing. Bleeding was reported in 5
      rivaroxaban cases, all in patients with chronic exposure; no deaths were
      reported. There were no adverse outcomes in pediatric patients. Coagulation
      parameters did not correlate well with bleeding. CONCLUSIONS: In our series, the
      greatest risk of adverse events was in patients chronically taking these agents,
      irrespective of excess dosing. Acute self-harm ingestions and accidental
      pediatric ingestions had few adverse effects, although massive overdose can lead
      to abnormal coagulation studies. It does not appear that single low-dose
      ingestions of either medication will lead to clinically significant bleeding. It
      may be possible to manage some pediatric exposures and most accidental ingestions
      with observation.

PMID- 24908446
TI  - Diagnostic laparoscopy for pneumatosis intestinalis: to do or not to do?
AB  - Pneumatosis intestinalis (PI) is a rare clinical condition, which is commonly
      associated with mesenteric vascular ischemia, bowel obstruction, and
      chemotherapy. Although the pathophysiology of PI remains unclear, 2 theories, one
      mechanical and the other bacterial, have been proposed. Nonoperative medical
      treatment and observation should be considered in mild cases, but occasionally,
      the situation requires emergency surgical intervention. In cases of suspectful
      complicated PI, the clinician should not avoid performing diagnostic laparoscopy
      to rule out bowel ischemia and perforation.

PMID- 24908447
TI  - Serial monitoring of sedation scores in benzodiazepine overdose.
AB  - Benzodiazepines are widely used for many diseases, and benzodiazepine overdose is
      globally increasing in proportion to its prescriptions. Although most
      benzodiazepine overdoses are known to be safe and nonfatal without coingestions,
      morbidity or mortality after benzodiazepine overdose is closely related with the
      duration of unconsciousness or depth of compromised airway. Proper use of
      flumazenil, a potent antidote of benzodiazepine, seems to accelerate the recovery
      from the toxicity after benzodiazepine overdose.However, as the case we present
      demonstrates, careful attention and repetitive evaluations before and after use
      of flumazenil may be needed in benzodiazepine overdose because resedation occurs
      in approximately 30% of total flumazenil-treated cases, which suggests that the
      risk of aspiration or incidental death after administrating flumazenil might be
      significant without careful monitoring.

PMID- 24908448
TI  - Two-stage laparoscopic treatment for strangulated inguinal, femoral and obturator
      hernias: totally extraperitoneal repair followed by intestinal resection assisted
      by intraperitoneal laparoscopic exploration.
AB  - PURPOSE: Total extraperitoneal preperitoneal (TEP) repair is widely used for
      inguinal, femoral, or obturator hernia treatment. However, mesh repair is not
      often used for strangulated hernia treatment if intestinal resection is required
      because of the risk of postoperative mesh infection. Complete mesh repair is
      required for hernia treatment to prevent postoperative recurrence, particularly
      in patients with femoral or obturator hernia. CASES: We treated four patients
      with inguinocrural and obturator hernias (a 72-year-old male with a right
      indirect inguinal hernia; an 83-year-old female with a right obturator hernia;
      and 86- and 82-year-old females with femoral hernias) via a two-stage
      laparoscopic surgery. All patients were diagnosed with intestinal obstruction due
      to strangulated hernia. First, the incarcerated small intestine was released and
      then laparoscopically resected. Further, 8-24 days after the first surgery,
      bilateral TEP repairs were performed in all patients; the postoperative course
      was uneventful in all patients, and they were discharged 5-10 days after TEP
      repair. At present, no hernia recurrence has been reported in any patient.
      CONCLUSION: The two-stage laparoscopic treatment is safe for treatment of
      strangulated inguinal, femoral, and obturator hernias, and complete mesh repair
      via the TEP method can be performed in elderly patients to minimize the
      occurrence of mesh infection.

PMID- 24908449
TI  - VKORC1 and CYP2C9 genotype distribution in Asian countries.
AB  - BACKGROUND: Warfarin is the most widely used anticoagulant all over the world for
      prevention and treatment of different thrombotic conditions. Polymorphisms in two
      genes i.e. CYP2C9 (Cytochrome P450 2C9) and VKORC1 (Vitamin K epoxide reductase
      complex subunit 1) play a major role in warfarin dose variation and its related
      adverse effects. Different ethnic groups have shown significant differences in
      dose requirement. METHOD: A systematic electronic search was carried out in
      PUBMED and ScienceDirect using different key words like, 'warfarin', 'CYP2C9',
      'VKORC1', 'pharmacokinetics', 'metabolites' and 'genetic'. Till date, data from
      15 Asian countries for CYP2C9 genotypes and 14 Asian countries for VKORC1
      genotypes could be retrieved. RESULTS: Approximately 90% of the subjects from
      East Asian countries were found to be carriers for VKORC1 1639 'A' or 1173 'T'
      allele (associated with low dose warfarin), while the prevalence of these alleles
      in the rest of the Asian countries (except Iran) i.e. South, South East, West and
      Central Asia ranged between 14 and 80%. Interestingly, an increase in carrier
      rate for CYP2C9 2 or 3 alleles was observed as we move from East to West Asia and
      an opposite trend was observed with VKORC1 1639 'A' or 1173 'T' alleles.
      Countries like Iran, Oman, India and Russia showed a drastic variation in the
      distribution pattern of these genotypes from that of the neighboring countries.
      CONCLUSION: The analysis further highlights the importance of genotype based
      warfarin dosing in each country. Since many Asian countries are still
      underrepresented in pharmacogenomic research, addition of data from these
      underrepresented countries will be beneficial for safe warfarin dosing in these
      patients.

PMID- 24908451
TI  - Preemies to preschoolers: tubing tiny tots and trauma FAQs, part 3.

PMID- 24908452
TI  - The sustainable development agenda and unmet need for sexual and reproductive
      health and rights.

PMID- 24908453
TI  - Poverty, food security and universal access to sexual and reproductive health
      services: a call for cross-movement advocacy against neoliberal globalisation.
AB  - Universal access to sexual and reproductive health services is one of the goals
      of the International Conference on Population and Development of 1994. The
      Millennium Development Goals were intended above all to end poverty. Universal
      access to health and health services are among the goals being considered for the
      post-2015 agenda, replacing or augmenting the MDGs. Yet we are not only far from
      reaching any of these goals but also appear to have lost our way somewhere along
      the line. Poverty and lack of food security have, through their multiple linkages
      to health and access to health care, deterred progress towards universal access
      to health services, including for sexual and reproductive health needs. A more
      insidious influence is neoliberal globalisation. This paper describes neoliberal
      globalisation and the economic policies it has engendered, the ways in which it
      influences poverty and food security, and the often unequal impact it has had on
      women as compared to men. It explores the effects of neoliberal economic policies
      on health, health systems, and universal access to health care services, and the
      implications for access to sexual and reproductive health. To be an advocate for
      universal access to health and health care is to become an advocate against
      neoliberal globalisation. 

PMID- 24908454
TI  - Sustainable development, demography and sexual and reproductive health:
      inseparable linkages and their policy implications.
AB  - The greatest challenge today is to meet the needs of current and future
      generations, of a large and growing world population, without imposing
      catastrophic pressures on the natural environment. Meeting this challenge depends
      on decisive policy changes in three areas: more inclusive economic growth,
      greener economic growth, and population policies. This article focuses on efforts
      to address and harness demographic changes for sustainable development, which are
      largely outside the purview of the current debate. Efforts to this end must be
      based on the recognition that demographic changes are the cumulative result of
      individual choices and opportunities, and that demographic changes are best
      addressed through policies that enlarge these choices and opportunities, with a
      focus on ensuring unrestricted and universal access to sexual and reproductive
      health information and services, empowering women to fully participate in social,
      economic and political life, and investing in the education of the younger
      generation beyond the primary level. The article provides a strong argument for
      why the Programme of Action that was agreed at the International Conference on
      Population and Development (ICPD) 20 years ago continues to hold important
      implications and lessons for the formulation of the post-2015 development agenda,
      which is expected to supersede the Millennium Development Goals (MDGs). 

PMID- 24908450
TI  - A genetic association study of D-dimer levels with 50K SNPs from a candidate gene
      chip in four ethnic groups.
AB  - INTRODUCTION: D-dimer, a fibrin degradation product, is related to risk of
      cardiovascular disease and venous thromboembolism. Genetic determinants of D
      dimer are not well characterized; notably, few data have been reported for
      African American (AA), Asian, and Hispanic populations. MATERIALS AND METHODS: We
      conducted a large-scale candidate gene association study to identify variants in
      genes associated with D-dimer levels in multi-ethnic populations. Four cohorts,
      comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286
      Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene
      Association Resource consortium, were assembled. Approximately 50,000 genotyped
      single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci
      were analyzed by linear regression, adjusting for age, sex, study site, and
      principal components in each cohort and ethnic group. Results across studies were
      combined within each ethnic group by meta-analysis. RESULTS: Twelve SNPs in
      coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were
      significantly associated with D-dimer level in EAs with p<2.0*10(-6). The signal
      for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in
      Hispanics (p=0.023), while that for the top functional SNP in FGA (rs6050) was
      replicated in AAs (p=0.006). No additional SNPs were significantly associated
      with D-dimer. CONCLUSIONS: Our study replicated previously reported associations
      of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the
      association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in
      Hispanics.

PMID- 24908455
TI  - A three-pronged approach to advocacy for sustainable national funding.
AB  - By and large, the financial commitments 179 nations made to the family planning
      and reproductive health components of ICPD in 1994 were not kept. While donors
      ramp up support for civil society advocacy in developing countries, in hopes of
      improving national funding and outcomes, recent trends in advocacy evaluation
      leave unanswered the broader question of whether/how international campaigning
      can appropriately and effectively strengthen national-level decision-making. This
      article provides background regarding the challenges in monitoring developing
      country contributions; summarizes current donor initiatives to strengthen civil
      society advocacy; and reviews theoretical approaches to assessing advocacy. The
      author identifies major advocacy limitations and proposes a three-pronged
      approach to harmonize international and national advocacy messages for improved,
      sustained increases in health funding and outcomes, namely, that local
      accountability is paramount, that national health programmes must be designed as
      legally binding entitlements, and that pro-health values and norms must be
      strengthened. 

PMID- 24908456
TI  - Population, sexual and reproductive health, rights and sustainable development:
      forging a common agenda.
AB  - This article suggests that sexual and reproductive health and rights activists
      seeking to influence the post-2015 international development paradigm must work
      with sustainable development advocates concerned with a range of issues,
      including climate change, environmental issues, and food and water security, and
      that a way of building bridges with these communities is to demonstrate how
      sexual and reproductive health and rights are relevant for these issues. An
      understanding of population dynamics, including urbanization and migration, as
      well as population growth, can help to clarify these links. This article
      therefore suggests that whether or not sexual and reproductive health and rights
      activists can overcome resistance to discussing "population", become more
      knowledgeable about other sustainable development issues, and work with others in
      those fields to advance the global sustainable development agenda are crucial
      questions for the coming months. The article also contends that it is possible to
      care about population dynamics (including ageing and problems faced by countries
      with a high proportion of young people) and care about human rights at the same
      time. It expresses concern that, if sexual and reproductive health and rights
      advocates do not participate in the population dynamics discourse, the field will
      be left free for those for whom respecting and protecting rights may be less of a
      priority. 

PMID- 24908457
TI  - Sexual and reproductive health and rights in the evolving post-2015 agenda:
      perspectives from key players from multilateral and related agencies in 2013.
AB  - This paper reports the views of participants from key multilaterals and related
      agencies in the evolving global negotiations on the post-2015 development agenda
      on the strategic location of sexual and reproductive health and rights. The
      research was carried out in June and July 2013, following the release of the
      report of the High-Level Panel of Eminent Persons on the Post-2015 Development
      Agenda, and comprised 40 semi-structured interviews with 57 participants and two
      e-mail respondents. All respondents were responsible for the post-2015 health and
      development agenda, or the post-2015 agenda more broadly, within their
      organisations. The interviews provide an insight into the intention to ensure
      that sexual and reproductive health and rights are integrated into the post-2015
      trajectory by key players who sit at the interface of UN and Member State
      interaction. They reveal both an awareness of the shortcomings of the Millennium
      Development Goal process and its impact on advocacy for sexual and reproductive
      health and rights in early post-2015 engagement, as well as the vulnerability of
      sexual and reproductive health and rights in the remaining phases of post-2015
      negotiations. Recent events bear these concerns out. Ensuring sexual and
      reproductive health and rights are included in the final post-2015 outcome
      document in the time remaining for negotiations, will be anything but a "doddle".

PMID- 24908458
TI  - Resilience, integrated development and family planning: building long-term
      solutions.
AB  - For the many individuals and communities experiencing natural disasters and
      environmental degradation, building resilience means becoming more proficient at
      anticipating, preventing, recovering, and rebuilding following negative shocks
      and stresses. Development practitioners have been working to build this
      proficiency in vulnerable communities around the world for several decades. This
      article first examines the meaning of resilience as a component of responding to
      disasters and some of the key components of building resilience. It then
      summarises approaches to resilience developed by the Rockefeller and Packard
      Foundations, the Intergovernmental Panel on Climate Change, USAID and DFID, which
      show how family planning services can contribute to resilience. Next, it gives
      some examples of how family planning has been integrated into some current
      environment and development programmes. Finally, it describes how these
      integrated programmes have succeeded in helping communities to diversify
      livelihoods, bolster community engagement and resilience, build new governance
      structures, and position women as agents of change. 

PMID- 24908459
TI  - Beginning with sustainable scale up in mind: initial results from a population,
      health and environment project in East Africa.
AB  - Small-scale pilot projects have demonstrated that integrated population, health
      and environment approaches can address the needs and rights of vulnerable
      communities. However, these and other types of health and development projects
      have rarely gone on to influence larger policy and programme development.
      ExpandNet, a network of health professionals working on scaling up, argues this
      is because projects are often not designed with future sustainability and scaling
      up in mind. Developing and implementing sustainable interventions that can be
      applied on a larger scale requires a different mindset and new approaches to
      small-scale/pilot testing. This paper shows how this new approach is being
      applied and the initial lessons from its use in the Health of People and
      Environment in the Lake Victoria Basin Project currently underway in Uganda and
      Kenya. Specific lessons that are emerging are: 1) ongoing, meaningful stakeholder
      engagement has significantly shaped the design and implementation, 2) multi
      sectoral projects are complex and striving for simplicity in the interventins is
      challenging, and 3) projects that address a sharply felt need experience
      substantial pressure for scale up, even before their effectiveness is
      established. Implicit in this paper is the recommendation that other projects
      would also benefit from applying a scale-up perspective from the outset. 

PMID- 24908460
TI  - Providing family planning services to remote communities in areas of high
      biodiversity through a Population-Health-Environment programme in Madagascar.
AB  - Population-Health-Environment (PHE) is an interdisciplinary model of programme
      design which recognises the complex interconnections between people, their health
      and their environment. PHE responds holistically to the challenges faced by
      ecosystems and the communities dependent on them, with thematically distinct but
      interconnected work strands sharing the same infrastructure, resources and goals.
      This has been shown to achieve better outcomes than tackling health and
      environmental issues in isolation. This paper shows how PHE programme design has
      been used by Blue Ventures for providing family planning services in a remote,
      biodiverse coastal region in southwest Madagascar. The PHE programme has
      integrated family planning services into a pre-existing, community-based
      conservation programme, aided by the established infrastructure and good
      community relations developed by the conservation workers. Implementation of the
      programme has led to a strong uptake of family planning services, and couples in
      the region are now able to make their own family planning choices. Successes and
      challenges of the programme are discussed. 

PMID- 24908461
TI  - Having fewer children makes it possible to educate them all: an ethnographic
      study of fertility decline in north-western Tigray, Ethiopia.
AB  - Education is presumed to play a decisive role in decreasing fertility rates. This
      article is about the role of education and other factors in fertility decline in
      the context of current Ethiopian policies on population and sustainable
      development, based on an ethnographic study of women's agency and girls' pursuit
      of education in one semi-urban and one rural area in north-western Tigray, in
      northern Ethiopia. Long-term environmental insecurity and scarcity of arable land
      for the younger generation in this area serve as important background. Another
      central issue in the study was the religious conditioning of women's choices,
      which stood out most clearly in the case of contraceptive use. The research
      consisted of in-depth, semi-structured interviews in 2008 with 25 purposively
      selected women from three generations, based on their life histories, linked with
      participatory observation and extended informal dialogue with women at different
      points during 2008-12. A smaller household survey with 170 women and a task
      based, education survey with 200 female and male students were also conducted in
      2009. In those cases where women's contestations of the authority of the Orthodox
      Christian priests concurred with current Ethiopian policies on fertility decline,
      this was based on what women defined as their own authority in reproductive
      matters linked with flexible adaptation to their life-situations. 

PMID- 24908462
TI  - Losing an only child: the one-child policy and elderly care in China.
AB  - China has had the one-child policy for more than 30 years. It reduced China's
      population growth within a short period of time and promoted economic
      development. However, it has also led to difficulties, and this paper focuses on
      those which pertain to ageing and losing one's only child. Approximately one
      million families have lost their only child in China. They suffer mentally and
      physically, and sometimes face social stigma and economic loss. What worries them
      most, however, is elderly care, which has become a severe crisis for the families
      who have lost their only children. This article draws upon several qualitative
      studies and 12 cases reported by the Chinese media in 2012 and 2013, and existing
      laws and policies for supporting those who have lost only children. It also
      analyses the current elderly care situation facing these families. The Chinese
      government has recognized the predicament and provides some help, which is
      increasing but is still not always adequate. To both sustain China's economic
      development and limit population growth, it is essential for the government to
      reform the one-child policy and provide a comprehensive support system for the
      families who have lost their only children, including financial relief and
      elderly care, and work to reduce stigma against these families. 

PMID- 24908463
TI  - Beyond bonus or bomb: upholding the sexual and reproductive health of young
      people.
AB  - Described as a blessing or a curse, a bonus or a bomb, the youthful population
      boom in the global South is thought to be the catalyst of present and future
      social change on a massive scale. These binary understandings of youth are
      popular among proponents of development programs aimed at young people, including
      for family planning. But dualistic, numbers-based theories oversimplify a much
      more complex picture. They narrow our perceptions of young populations and, when
      lacking more detailed understanding based in youth experience, have the potential
      to constrict sexual and reproductive health and rights. Instead, youth-friendly,
      inclusive sexual and reproductive health policy should build from young peoples'
      visions and diverse realities.

PMID- 24908464
TI  - "Female condoms are_____": bringing local voices to decision-makers through a
      film contest.

PMID- 24908465
TI  - Conscientious objection, barriers, and abortion in the case of rape: a study
      among physicians in Brazil.
AB  - In Brazil, to have a legal abortion in the case of rape, the woman's statement
      that rape has occurred is considered sufficient to guarantee the right to
      abortion. The aim of this study was to understand the practice and opinions about
      providing abortion in the case of rape among obstetricians-gynecologists (OBGYNs)
      in Brazil. A mixed-method study was conducted from April to July 2012 with 1,690
      OBGYNs who responded to a structured, electronic, self-completed questionnaire.
      In the quantitative phase, 81.6% of the physicians required police reports or
      judicial authorization to guarantee the care requested. In-depth telephone
      interviews with 50 of these physicians showed that they frequently tested women's
      rape claim by making them repeat their story to several health professionals;
      43.5% of these claimed conscientious objection when they were uncertain whether
      the woman was telling the truth. The moral environment of illegal abortion alters
      the purpose of listening to a patient - from providing care to passing judgement
      on her. The data suggest that women's access to legal abortion is being blocked
      by these barriers in spite of the law. We recommend that FEBRASGO and the
      Ministry of Health work together to clarify to physicians that a woman's
      statement that rape occurred should allow her to access a legal abortion. 

PMID- 24908466
TI  - Women's perceptions about abortion in their communities: perspectives from
      western Kenya.
AB  - Unsafe abortion in Kenya is a leading cause of maternal morbidity and mortality.
      In October 2012, we sought to understand the methods married women aged 24-49 and
      young, unmarried women aged <= 20 used to induce abortion, the providers they
      utilized and the social, economic and cultural norms that influenced women's
      access to safe abortion services in Bungoma and Trans Nzoia counties in western
      Kenya. We conducted five focus groups with young women and five with married
      women in rural and urban communities in each county. We trained local
      facilitators to conduct the focus groups in Swahili or English. All focus groups
      were audiotaped, transcribed, translated, computerized, and coded for analysis.
      Abortion outside public health facilities was mentioned frequently. Because of
      the need for secrecy to avoid condemnation, uncertainty about the law, and
      perceived higher cost of safer abortion methods, women sought unsafe abortions
      from community midwives, drug sellers and/or untrained providers at lower cost.
      Many groups believed that abortion was safer at higher gestational ages, but that
      there was no such thing as a safe abortion method. Our aim was to inform the
      design of a community-based intervention on safe abortion for women. Barriers to
      seeking safe services such as high cost, perceived illegality, and fear of
      insults and abuse at public facilities among both age groups must be addressed. 

PMID- 24908467
TI  - Induced abortion patterns and determinants among married women in China: 1979 to
      2010.
AB  - China has launched the one-child policy to control its rapidly expanding
      population since 1979. Local governments, tasked with limiting regional birth
      rates, commonly imposed induced abortions. After 1994, China's family planning
      policy was relatively loosened and mandatory induced abortion gradually gave way
      to client-centered and informed-choice contraceptive policy and the
      "Compensation" Fee policy. This study assesses trends in and determinants of
      induced abortion among married women aged 20-49 in China from 1979 to 2010, using
      data from national statistics and nationally representative sample surveys. The
      incidence of induced abortions among married women aged 20-49 began to decrease
      in the mid-1990s. The induced abortion rate reached its highest level in the
      early 1980s (56.07%) and its lowest level in the 2000s (18.04%), with an average
      annual rate of 28.95% among married women 20-49 years old. The likelihood of a
      pregnant woman undergoing an induced abortion during this period depended not
      only on individual characteristics (including ethnicity, age, education level,
      household registration, number of children, and sex of children), but also on the
      stringency of the family planning policy in place. The less stringent the family
      planning policy, the less likely married women were to undergo an induced
      abortion. 

PMID- 24908468
TI  - Female genital cutting in Hargeisa, Somaliland: is there a move towards less
      severe forms?
AB  - According to several sources, little progress is being made in eliminating the
      cutting of female genitalia. This paper, based on qualitative interviews and
      observations, explores perceptions of female genital cutting and elimination of
      the phenomenon in Hargeisa, Somaliland. Two main groups of participants were
      interviewed: (1) 22 representatives of organisations whose work directly relates
      to female genital cutting; and (2) 16 individuals representing different groups
      of society. It was found that there is an increasing use of medical staff and
      equipment when a girl undergoes the procedure of female genital cutting; the use
      of terminology is crucial in understanding current perceptions of female genital
      cutting; religion is both an important barrier and facilitator of elimination;
      and finally, traditional gender structures are currently being challenged in
      Hargeisa. The findings of this study suggest that it is important to consider
      current perceptions on practices of female genital cutting and on abandonment of
      female genital cutting, in order to gain useful knowledge on the issue of
      elimination. The study concludes that elimination of female genital cutting is a
      multifaceted process which is constantly negotiated in a diversity of social
      settings. 

PMID- 24908469
TI  - The use of social media among adolescents in Dar es Salaam and Mtwara, Tanzania.
AB  - Social media form part of the rapid worldwide digital development that is re
      shaping the life of many young people. While the use of social media by youths is
      increasingly researched in the North, studies about youth in the South are
      missing. It therefore remains unclear how social media can be included in
      interventions that aim at informing young people in many countries of the global
      South about sexual and reproductive health. This paper presents findings of a
      mixed-methods study of young people's user behaviour on the internet and
      specifically of social media as a platform for sexual health promotion in
      Tanzania. The study used questionnaires with 60 adolescents and in-depth
      interviews with eight students aged 15 to 19 years in Dar es Salaam, and in
      Mtwara, Southern Tanzania. Findings show that youth in Dar es Salaam and Mtwara
      access the internet mainly through mobile phones. Facebook is by far the most
      popular internet site. Adolescents highlighted their interest in reproductive and
      sexual health messages and updates being delivered through humorous posts, links
      and clips, as well as by youth role models like music stars and actors that are
      entertaining and reflect up-to-date trends of modern youth culture. 

PMID- 24908470
TI  - Statement from the International Campaign for Women's Right to Safe Abortion: 12
      May 2014.

PMID- 24908471
TI  - Statement from the University of the Witwatersrand pertaining to anti
      homosexuality legislation in Africa.

PMID- 24908472
TI  - Community consensus statement on the use of antiretroviral therapy in preventing
      HIV transmission.

PMID- 24908473
TI  - Brugada syndrome and idiopathic left ventricular tachycardia unmasked by exercise
      and a class Ic drug.
AB  - The patient was a 33-year-old male. Twenty years ago, he underwent radiofrequency
      catheter ablation for idiopathic sustained monomorphic ventricular tachycardia
      (VT) with an RBBB and superior axis pattern. The VT was inducible by programmed
      stimulation and entrained by rapid pacing. At this presentation, he developed
      palpitation and VT with the same morphology at the peak exercise on a treadmill
      with appearance of typical ECG pattern for Brugada syndrome (BrS). Pilsicainide
      induced the typical ECG pattern and premature ventricular beats (PVBs) of the
      same morphology as VT. The relationship between BrS and VT of left ventricular
      origin was discussed. 

PMID- 24908474
TI  - Metastatic Castration-resistant Prostate Cancer: Piling Up the Benefits of
      Chemotherapy.

PMID- 24908475
TI  - Metformin to prevent prostate cancer: a call to unite.

PMID- 24908476
TI  - Sleeping at work: not all about location, location, location.
AB  - Working arrangements in industries that use non-standard hours sometimes
      necessitate an 'onsite' workforce where workers sleep in accommodation within or
      adjacent to the workplace. Of particular relevance to these workers is the widely
      held (and largely anecdotal) assumption that sleep at home is better than sleep
      away, particularly when away for work. This narrative review explores the idea
      that sleep outcomes in these unique work situations are the product of an
      interaction between numerous factors including timing and duration of breaks,
      commute length, sleeping environment (noise, movement, vibration, light),
      circadian phase, demographic factors and familiarity with the sleep location.
      Based on the data presented in this review, it is our contention that the
      location of sleep, whilst important, is secondary to other factors such as the
      timing and duration of sleep periods. We suggest that future research should
      include measures that allow conceptualisation of other critical factors such as
      familiarity with the sleeping environment. 

PMID- 24908477
TI  - CaV1.2 calcium channels: just cut out to be regulated?
AB  - Tight regulation of calcium entry through the L-type calcium channel CaV1.2
      ensures optimal excitation-response coupling. In this issue of Neuron,
      Michailidis et al. (2014) demonstrate that CaV1.2 activity triggers negative
      feedback regulation through proteolytic cleavage of the channel within the core
      of the pore-forming subunit.

PMID- 24908478
TI  - Enhance your chance with the TANs: tonically active neurons support learning in
      the ventral striatum.
AB  - The striatum is crucial for the correct learning and control of goal-directed
      behavior and habitual actions. Here in this issue of Neuron, Atallah et al.
      (2014) show that both reinforcement-based learning and control parameters are
      reflected in the neural activity of the ventromedial striatum.

PMID- 24908479
TI  - Listening for the right sounds.
AB  - In this issue of Neuron, Rodgers and DeWeese (2014) developed a new paradigm in
      which rats had to select or ignore an auditory stimulus, depending on its
      context. The authors recorded neurons in primary auditory and medial prefrontal
      cortex. Surprisingly, they found that stimulus context had the largest effect in
      the moments before the stimulus was presented. 

PMID- 24908480
TI  - The double helix takes the witness stand: behavioral and neuropsychiatric
      genetics in court.
AB  - Data on neuropsychiatric and behavioral genetics have attracted legal interest,
      as attorneys explore their use in criminal and civil cases. These developments
      may assist judges and juries in making difficult judgments-but they bring
      substantial risk of misinterpretation and misuse. 

PMID- 24908481
TI  - Decision making: the neuroethological turn.
AB  - Neuroeconomics applies models from economics and psychology to inform
      neurobiological studies of choice. This approach has revealed neural signatures
      of concepts like value, risk, and ambiguity, which are known to influence
      decision making. Such observations have led theorists to hypothesize a single,
      unified decision process that mediates choice behavior via a common neural
      currency for outcomes like food, money, or social praise. In parallel, recent
      neuroethological studies of decision making have focused on natural behaviors
      like foraging, mate choice, and social interactions. These decisions strongly
      impact evolutionary fitness and thus are likely to have played a key role in
      shaping the neural circuits that mediate decision making. This approach has
      revealed a suite of computational motifs that appear to be shared across a wide
      variety of organisms. We argue that the existence of deep homologies in the
      neural circuits mediating choice may have profound implications for understanding
      human decision making in health and disease. 

PMID- 24908483
TI  - Clathrin/AP-2 mediate synaptic vesicle reformation from endosome-like vacuoles
      but are not essential for membrane retrieval at central synapses.
AB  - Neurotransmission depends on presynaptic membrane retrieval and local reformation
      of synaptic vesicles (SVs) at nerve terminals. The mechanisms involved in these
      processes are highly controversial with evidence being presented for SV membranes
      being retrieved exclusively via clathrin-mediated endocytosis (CME) from the
      plasma membrane or via ultrafast endocytosis independent of clathrin. Here we
      show that clathrin and its major adaptor protein 2 (AP-2) in addition to the
      plasma membrane operate at internal endosome-like vacuoles to regenerate SVs but
      are not essential for membrane retrieval. Depletion of clathrin or conditional
      knockout of AP-2 result in defects in SV reformation and an accumulation of
      endosome-like vacuoles generated by clathrin-independent endocytosis (CIE) via
      dynamin 1/3 and endophilin. These results together with theoretical modeling
      provide a conceptual framework for how synapses capitalize on clathrin
      independent membrane retrieval and clathrin/AP-2-mediated SV reformation from
      endosome-like vacuoles to maintain excitability over a broad range of stimulation
      frequencies. 

PMID- 24908482
TI  - Amygdala microcircuits controlling learned fear.
AB  - We review recent work on the role of intrinsic amygdala networks in the
      regulation of classically conditioned defensive behaviors, commonly known as
      conditioned fear. These new developments highlight how conditioned fear depends
      on far more complex networks than initially envisioned. Indeed, multiple parallel
      inhibitory and excitatory circuits are differentially recruited during the
      expression versus extinction of conditioned fear. Moreover, shifts between
      expression and extinction circuits involve coordinated interactions with
      different regions of the medial prefrontal cortex. However, key areas of
      uncertainty remain, particularly with respect to the connectivity of the
      different cell types. Filling these gaps in our knowledge is important because
      much evidence indicates that human anxiety disorders results from an abnormal
      regulation of the networks supporting fear learning. 

PMID- 24908484
TI  - Non-cell-autonomous mechanism of activity-dependent neurotransmitter switching.
AB  - Activity-dependent neurotransmitter switching engages genetic programs regulating
      transmitter synthesis, but the mechanism by which activity is transduced is
      unknown. We suppressed activity in single neurons in the embryonic spinal cord to
      determine whether glutamate-gamma-aminobutyric acid (GABA) switching is cell
      autonomous. Transmitter respecification did not occur, suggesting that it is
      homeostatically regulated by the level of activity in surrounding neurons. Graded
      increase in the number of silenced neurons in cultures led to graded decrease in
      the number of neurons expressing GABA, supporting non-cell-autonomous transmitter
      switching. We found that brain-derived neurotrophic factor (BDNF) is expressed in
      the spinal cord during the period of transmitter respecification and that spike
      activity causes release of BDNF. Activation of TrkB receptors triggers a
      signaling cascade involving JNK-mediated activation of cJun that regulates tlx3,
      a glutamate/GABA selector gene, accounting for calcium-spike BDNF-dependent
      transmitter switching. Our findings identify a molecular mechanism for activity
      dependent respecification of neurotransmitter phenotype in developing spinal
      neurons.

PMID- 24908485
TI  - Age-related homeostatic midchannel proteolysis of neuronal L-type voltage-gated
      Ca2+ channels.
AB  - Neural circuitry and brain activity depend critically on proper function of
      voltage-gated calcium channels (VGCCs), whose activity must be tightly
      controlled. We show that the main body of the pore-forming alpha1 subunit of
      neuronal L-type VGCCs, Cav1.2, is proteolytically cleaved, resulting in Cav1.2
      fragment channels that separate but remain on the plasma membrane. This
      "midchannel" proteolysis is regulated by channel activity, involves the Ca(2+)
      dependent protease calpain and the ubiquitin-proteasome system, and causes
      attenuation and biophysical alterations of VGCC currents. Recombinant Cav1.2
      fragment channels mimicking the products of midchannel proteolysis do not form
      active channels on their own but, when properly paired, produce currents with
      distinct biophysical properties. Midchannel proteolysis increases dramatically
      with age and can be attenuated with an L-type VGCC blocker in vivo. Midchannel
      proteolysis represents a novel form of homeostatic negative-feedback processing
      of VGCCs that could profoundly affect neuronal excitability, neurotransmission,
      neuroprotection, and calcium signaling in physiological and disease states.

PMID- 24908486
TI  - Microtubule minus-end binding protein CAMSAP2 controls axon specification and
      dendrite development.
AB  - In neurons, most microtubules are not associated with a central microtubule
      organizing center (MTOC), and therefore, both the minus and plus-ends of these
      non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends
      are well established as dynamic regulatory sites in numerous processes, but the
      role of microtubule minus-ends has remained poorly understood. Using live-cell
      imaging, high-resolution microscopy, and laser-based microsurgery techniques, we
      show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes
      to non-centrosomal microtubule minus-ends and is required for proper microtubule
      organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is
      required for neuronal polarity, axon specification, and dendritic branch
      formation in vitro and in vivo. Furthermore, we found that non-centrosomal
      microtubules in dendrites are largely generated by gamma-Tubulin-dependent
      nucleation. We propose a two-step model in which gamma-Tubulin initiates the
      formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free
      microtubule minus-ends in order to control neuronal polarity and development.

PMID- 24908487
TI  - SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain
      receptor in peripheral glia.
AB  - Balancing trophic and apoptotic cues is critical for development and regeneration
      of neuronal circuits. Here we identify SorCS2 as a proneurotrophin (proNT)
      receptor, mediating both trophic and apoptotic signals in conjunction with
      p75(NTR). CNS neurons, but not glia, express SorCS2 as a single-chain protein
      that is essential for proBDNF-induced growth cone collapse in developing
      dopaminergic processes. SorCS2- or p75(NTR)-deficient in mice caused reduced
      dopamine levels and metabolism and dopaminergic hyperinnervation of the frontal
      cortex. Accordingly, both knockout models displayed a paradoxical behavioral
      response to amphetamine reminiscent of ADHD. Contrary, in PNS glia, but not in
      neurons, proteolytic processing produced a two-chain SorCS2 isoform that mediated
      proNT-dependent Schwann cell apoptosis. Sciatic nerve injury triggered generation
      of two-chain SorCS2 in p75(NTR)-positive dying Schwann cells, with apoptosis
      being profoundly attenuated in Sorcs2(-/-) mice. In conclusion, we have
      demonstrated that two-chain processing of SorCS2 enables neurons and glia to
      respond differently to proneurotrophins.

PMID- 24908488
TI  - Microsecond dissection of neurotransmitter release: SNARE-complex assembly
      dictates speed and Ca2+ sensitivity.
AB  - SNARE-complex assembly mediates synaptic vesicle fusion during neurotransmitter
      release and requires that the target-SNARE protein syntaxin-1 switches from a
      closed to an open conformation. Although many SNARE proteins are available per
      vesicle, only one to three SNARE complexes are minimally needed for a fusion
      reaction. Here, we use high-resolution measurements of synaptic transmission in
      the calyx-of-Held synapse from mutant mice in which syntaxin-1 is rendered
      constitutively open and SNARE-complex assembly is enhanced to examine the
      relation between SNARE-complex assembly and neurotransmitter release. We show
      that enhancing SNARE-complex assembly dramatically increases the speed of evoked
      release, potentiates the Ca(2+)-affinity of release, and accelerates fusion-pore
      expansion during individual vesicle fusion events. Our data indicate that the
      number of assembled SNARE complexes per vesicle during fusion determines the
      presynaptic release probability and fusion kinetics and suggest a mechanism
      whereby proteins (Munc13 or RIM) may control presynaptic plasticity by regulating
      SNARE-complex assembly.

PMID- 24908489
TI  - Zinc dynamics and action at excitatory synapses.
AB  - Decades after the discovery that ionic zinc is present at high levels in
      glutamatergic synaptic vesicles, where, when, and how much zinc is released
      during synaptic activity remains highly controversial. Here we provide a
      quantitative assessment of zinc dynamics in the synaptic cleft and clarify its
      role in the regulation of excitatory neurotransmission by combining synaptic
      recordings from mice deficient for zinc signaling with Monte Carlo simulations.
      Ambient extracellular zinc levels are too low for tonic occupation of the GluN2A
      specific nanomolar zinc sites on NMDA receptors (NMDARs). However, following
      short trains of physiologically relevant synaptic stimuli, zinc transiently rises
      in the cleft and selectively inhibits postsynaptic GluN2A-NMDARs, causing changes
      in synaptic integration and plasticity. Our work establishes the rules of zinc
      action and reveals that zinc modulation extends beyond hippocampal mossy fibers
      to excitatory SC-CA1 synapses. By specifically moderating GluN2A-NMDAR signaling,
      zinc acts as a widespread activity-dependent regulator of neuronal circuits.

PMID- 24908490
TI  - Dynamic encoding of perception, memory, and movement in a C. elegans chemotaxis
      circuit.
AB  - Brain circuits endow behavioral flexibility. Here, we study circuits encoding
      flexible chemotaxis in C. elegans, where the animal navigates up or down NaCl
      gradients (positive or negative chemotaxis) to reach the salt concentration of
      previous growth (the set point). The ASER sensory neuron mediates positive and
      negative chemotaxis by regulating the frequency and direction of reorientation
      movements in response to salt gradients. Both salt gradients and set point memory
      are encoded in ASER temporal activity patterns. Distinct temporal activity
      patterns in interneurons immediately downstream of ASER encode chemotactic
      movement decisions. Different interneuron combinations regulate positive versus
      negative chemotaxis. We conclude that sensorimotor pathways are segregated
      immediately after the primary sensory neuron in the chemotaxis circuit, and
      sensory representation is rapidly transformed to motor representation at the
      first interneuron layer. Our study reveals compact encoding of perception,
      memory, and locomotion in an experience-dependent navigational behavior in C.
      elegans.

PMID- 24908492
TI  - Neural correlates of task switching in prefrontal cortex and primary auditory
      cortex in a novel stimulus selection task for rodents.
AB  - Animals can selectively respond to a target sound despite simultaneous
      distractors, just as humans can respond to one voice at a crowded cocktail party.
      To investigate the underlying neural mechanisms, we recorded single-unit activity
      in primary auditory cortex (A1) and medial prefrontal cortex (mPFC) of rats
      selectively responding to a target sound from a mixture. We found that
      prestimulus activity in mPFC encoded the selection rule-which sound from the
      mixture the rat should select. Moreover, electrically disrupting mPFC
      significantly impaired performance. Surprisingly, prestimulus activity in A1 also
      encoded selection rule, a cognitive variable typically considered the domain of
      prefrontal regions. Prestimulus changes correlated with stimulus-evoked changes,
      but stimulus tuning was not strongly affected. We suggest a model in which
      anticipatory activation of a specific network of neurons underlies the selection
      of a sound from a mixture, giving rise to robust and widespread rule encoding in
      both brain regions.

PMID- 24908491
TI  - Neurons in the ventral striatum exhibit cell-type-specific representations of
      outcome during learning.
AB  - The ventromedial striatum (VMS) is a node in circuits underpinning both affect
      and reinforcement learning. The cellular bases of these functions and especially
      their potential linkages have been unclear. VMS cholinergic interneurons,
      however, have been singled out as being related both to affect and to
      reinforcement-based conditioning, raising the possibility that unique aspects of
      their signaling could account for these functions. Here we show that VMS
      tonically active neurons (TANs), including putative cholinergic interneurons,
      generate unique bidirectional outcome responses during reward-based learning,
      reporting both positive (reward) and negative (reward omission) outcomes when
      behavioral change is prompted by switches in reinforcement contingencies. VMS
      output neurons (SPNs), by contrast, are nearly insensitive to switches in
      reinforcement contingencies, gradually losing outcome signaling while maintaining
      responses at trial initiation and goal approach. Thus, TANs and SPNs in the VMS
      provide distinct signals optimized for different aspects of the learning process.

PMID- 24908493
TI  - Brain networks for exploration decisions utilizing distinct modeled information
      types during contextual learning.
AB  - Exploration permits acquisition of the most relevant information during learning.
      However, the specific information needed, the influences of this information on
      decision making, and the relevant neural mechanisms remain poorly understood. We
      modeled distinct information types available during contextual association
      learning and used model-based fMRI in conjunction with manipulation of
      exploratory decision making to identify neural activity associated with
      information-based decisions. We identified hippocampal-prefrontal contributions
      to advantageous decisions based on immediately available novel information,
      distinct from striatal contributions to advantageous decisions based on the sum
      total available (accumulated) information. Furthermore, network-level
      interactions among these regions during exploratory decision making were related
      to learning success. These findings link strategic exploration decisions during
      learning to quantifiable information and advance understanding of adaptive
      behavior by identifying the distinct and interactive nature of brain-network
      contributions to decisions based on distinct information types. 

PMID- 24908495
TI  - Comparison of phenotypic tests for the detection of metallo-beta-lactamases in
      clinical isolates of Pseudomonas aeruginosa.
AB  - Metallo-beta-lactamase (MBL)-producing gram-negative bacteria are an increasing
      public health concern worldwide. Screening tests for the rapid and specific
      identification of these pathogens are essential, and should be included among
      routine diagnostics in laboratories. This study aimed to determine the MBL
      frequency among carbapenem-resistant Pseudomonas aeruginosa isolates, and to
      evaluate the accuracy of different tests in screening for MBL production. From
      January 2001 to December 2008, a total of 142 imipenem-non-susceptible P.
      aeruginosa strains were isolated from distinct clinical samples from hospitalized
      patients. These isolates were examined by PCR, MBL E-test, double-disk synergy
      test (DDST), and combined disk (CD) test. The minimal inhibitory concentration
      (MIC; MUg/mL) was determined by agar dilution, and pulsed field gel
      electrophoresis (PFGE) was performed on all samples. Sequencing was performed to
      confirm and define the MBL variant and subtype. Using PCR and DNA sequence
      analysis, 93 strains were confirmed positive for MBLs, 91 strains for the blaSPM
      1 gene, 1 strain for the blaIMP-1 gene, and 1 strain for the blaIMP-16 gene. PFGE
      displayed a clonal pattern. The sensitivities, specificities, positive and
      negative predictive values were evaluated for all tests. The DDST assay (CAZ-MPA)
      was the optimal method for screening MBL production in P. aeruginosa strains.
      However, the results of the CD assay (IMP/EDTA) showed close agreement with those
      of the DDST. In addition, the CD assay allowed a more objective interpretation
      and did not require the use of a toxic substance. 

PMID- 24908496
TI  - [Is Influenza coming earlier this season? How do I report?].

PMID- 24908494
TI  - Fibromyalgia and sleep in animal models: a current overview and future
      directions.
AB  - Sleep disorders are highly prevalent in patients with fibromyalgia (FM). Many of
      the daytime symptoms, such as chronic pain and fatigue, may be related to the non
      restorative sleep patterns associated with the disease. Pain influences the sleep
      process and sleep disturbances decrease the pain threshold in a reciprocal
      framework. Thus, understanding the link between sleep and FM has become an
      important research topic in basic science. Therefore, in the current review we
      connect these topics and provide some insights into the cyclic relationship
      between sleep and pain, which has been addressed mainly in animal models.
      Additionally, we highlight the urgent need for sleep studies in FM animal models,
      which might improve the knowledge base and accelerate advances in this field. 

PMID- 24908498
TI  - Development of eco-friendly porous fired clay bricks using pore-forming agents: a
      review.
AB  - Today, clay bricks are facing technological challenges and are uncompetitive
      compared to materials such as concrete. Their performance must be improved if
      they are to stand up to the competition. Increasing environmental concerns over
      the accumulation of unmanaged wastes from agricultural or industrial productions
      have made these good candidates for incorporation into building materials to
      improve their performance. This process leads to the formation of pores in the
      bricks, producing lightweight and sustainable building materials. This paper
      reviews the different pore-forming agents from renewable or mineral resources as
      described in the literature. It also presents the impact of pore-forming agents
      on the physical, mechanical and thermal properties of clay bricks. 

PMID- 24908497
TI  - [Usefulness of human papillomavirus testing in anal intraepithelial neoplasia
      screening in a risk behaviour population].
AB  - INTRODUCTION: The incidence of intraepithelial anal neoplasia is increasing in
      certain risk behaviour groups, and human papillomavirus (HPV) infection is
      involved in its pathogenesis. The systematic use of anal cytology, and more
      recently HPV detection by hybrid capture and genotyping, have been introduced
      into screening programs in recent decades. MATERIAL AND METHODS: A retrospective
      cohort study was carried out on individuals with risk behaviours of developing
      intraepithelial anal neoplasia and who attended Sexually Transmitted Infections
      clinics in the Dermatology area of the Hospital Costa del Sol from January 2010
      to December 2012. The intraepithelial anal neoplasia screening was performed
      using anal cytology and HPV genotyping. RESULTS: Half (50%) of the study
      population were HIV positive. A high frequency of anal dysplasia and presence of
      HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant
      association (P<.005) was obtained between the presence of high-risk HPV genotypes
      and the presence of high-grade dysplasia in the second directed cytology. HPV
      genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were
      under-diagnosed in the first cytology. CONCLUSION: Cases of high-grade dysplasia
      can be under-diagnosed by a first anal cytology. Detection of HPV can supplement
      this procedure, leading to the identification of those patients most at risk of
      developing high-grade anal dysplasia.

PMID- 24908499
TI  - Predicting pharmacists' adjustment of medication regimens in Ramadan using the
      Theory of Planned Behavior.
AB  - BACKGROUND: During Ramadan, many Muslim patients may choose to abstain from food,
      drink and oral medications from dawn to sunset. OBJECTIVES: This study explored
      the utility of the Theory of Planned Behavior (TPB) model in predicting community
      pharmacists' Medication Regimen Adjustment (MRA) behavior for patients during
      Ramadan. METHODS: A sample of pharmacists was drawn from a recent list of
      community pharmacies in the Alexandria governorate. A cross-sectional, self
      administered survey was completed by community pharmacists to determine their
      attitudes and behaviors regarding adjustment of medication regimens around
      Ramadan. Multiple linear regression was used to predict MRA as a function of the
      TPB constructs and four other factors - "pharmacist initiation of the
      conversation on MRA," "number of hours worked," "age," and "religion" of
      pharmacist. RESULTS: Two hundred seventy-seven (92.9%) of the 298 approached
      pharmacists participated. While 94.2% reported performing one or more kinds of
      MRA around Ramadan for at least one patient, the majority of these were for a
      small percentage of patients. The most common MRA was changing the frequency of
      taking the medication followed by the dose of the medication, the dosage form of
      the medication and the medication itself. Statistically significant predictors of
      MRA in the final model included patient social pressure (PSP) (beta = 0.274, P <
      0.001), pharmacist perceived behavioral capability (PBC) (beta = 0.217, P <
      0.001), pharmacist perceived patient benefit (PPB) (beta = 0.207, P = 0.001),
      initiating communication (beta = 0.167, P = 0.001) and the number of working
      hours (beta = 0.145, P = 0.005). CONCLUSIONS: The TPB appears to have utility in
      predicting pharmacists' MRA behavior. Pharmacists may be open to a larger MRA
      role than they are currently performing. There is a need to prepare pharmacists
      who are frequently requested to adjust patients' medication regimens to make sure
      they provide a safe transition for fasting patients into and out of Ramadan.

PMID- 24908500
TI  - In vitro studies of enzymatic properties of starch synthases and interactions
      between starch synthase I and starch branching enzymes from rice.
AB  - The present study was conducted to characterize the functions of the major starch
      synthase (SS) isozymes SSI, SSIIa, and SSIIIa in rice endosperm and their
      functional interaction with starch branching enzyme (BE), by using their purified
      recombinant proteins. All the SS isozymes had similarly significant activities
      toward branched glucans such as amylopecin and glycogen whereas they scarcely
      showed activities toward maltohexaose. In vitro studies indicate that SSI mainly
      attacked A and B chains with degree of polymerization (DP) of 6 and 7 in their
      external segments and elongated them to DP8. It is likely that SSIIa and SSIIIa
      produced wider ranges of intermediate chains and long chains, respectively. This
      study also revealed that without addition of exogenous primer, the glucan
      synthesis of SSI in the presence of ?0.3 M citrate was accelerated by the
      addition of any of the rice BE isozymes- BEI, BEIIa, or BEIIb, whereas no such
      interaction occurred between SSIIa or SSIIIa with any of the BEs. The SSI-BE
      unprimed glucan synthesis absolutely required citrate. The interaction between
      SSI and BE was established by stimulation of SSI activity with BE and by
      activation of the BE activity by SSI.

PMID- 24908501
TI  - Association analysis of single nucleotide polymorphisms in candidate genes with
      root traits in maize (Zea mays L.) seedlings.
AB  - Several genes involved in maize root development have been isolated.
      Identification of SNPs associated with root traits would enable the selection of
      maize lines with better root architecture that might help to improve N uptake,
      and consequently plant growth particularly under N deficient conditions. In the
      present study, an association study (AS) panel consisting of 74 maize inbred
      lines was screened for seedling root traits in 6, 10, and 14-day-old seedlings.
      Allele re-sequencing of candidate root genes Rtcl, Rth3, Rum1, and Rul1 was also
      carried out in the same AS panel lines. All four candidate genes displayed
      different levels of nucleotide diversity, haplotype diversity and linkage
      disequilibrium. Gene based association analyses were carried out between
      individual polymorphisms in candidate genes, and root traits measured in 6, 10,
      and 14-day-old maize seedlings. Association analyses revealed several
      polymorphisms within the Rtcl, Rth3, Rum1, and Rul1 genes associated with
      seedling root traits. Several nucleotide polymorphisms in Rtcl, Rth3, Rum1, and
      Rul1 were significantly (P<0.05) associated with seedling root traits in maize
      suggesting that all four tested genes are involved in the maize root development.
      Thus considerable allelic variation present in these root genes can be exploited
      for improving maize root characteristics. 

PMID- 24908502
TI  - Turning heads: the biology of solar tracking in sunflower.
AB  - Solar tracking in the common sunflower, Helianthus annuus, is a dramatic example
      of a diurnal rhythm in plants. During the day, the shoot apex continuously
      reorients, following the sun's relative position so that the developing heads
      track from east to west. At night, the reverse happens, and the heads return and
      face east in anticipation of dawn. This daily cycle dampens and eventually stops
      at anthesis, after which the sunflower head maintains an easterly orientation.
      Although shoot apical heliotropism has long been the subject of physiological
      studies in sunflower, the underlying developmental, cellular, and molecular
      mechanisms that drive the directional growth and curvature of the stem in
      response to extrinsic and perhaps intrinsic cues are not known. Furthermore, the
      ecological functions of solar tracking and the easterly orientation of mature
      heads have been the subject of significant but unresolved speculation. In this
      review, we discuss the current state of knowledge about this complex, dynamic
      trait. Candidate mechanisms that may contribute to daytime and nighttime movement
      are highlighted, including light signaling, hormonal action, and circadian
      regulation of growth pathways. The merits of the diverse hypotheses advanced to
      explain the adaptive significance of heliotropism in sunflower are also
      considered. 

PMID- 24908503
TI  - Genotypic variation of zinc and selenium concentration in grains of Brazilian
      wheat lines.
AB  - Exploration of genetic resources for micronutrient concentrations facilitates the
      breeding of nutrient-dense crops, which is increasingly seen as an additional,
      sustainable strategy to combat global micronutrient deficiency. In this work, we
      evaluated genotypic variation in grain nutrient concentrations of 20 Brazil wheat
      (Triticum aestivum L.) accessions in response to zinc (Zn) and Zn plus selenium
      (Se) treatment. Zn and Se concentrations in grains exhibited 2- and 1.5-fold
      difference, respectively, between these wheat accessions. A variation of up to 3
      fold enhancement of grain Zn concentration was observed when additionally Zn was
      supplied, indicating a wide range capacity of the wheat lines in accumulating Zn
      in grains. Moreover, grain Zn concentration was further enhanced in some lines
      following supply of Zn plus Se, showing stimulative effect by Se and the
      feasibility of simultaneous biofortification of Zn and Se in grains of some wheat
      lines. In addition, Se supply with Zn improved the accumulation of another
      important micronutrient, iron (Fe), in grains of half of these wheat lines,
      suggesting a beneficial role of simultaneous biofortification of Zn with Se. The
      significant diversity in these wheat accessions offers genetic potential for
      developing cultivars with better ability to accumulate important micronutrients
      in grains. 

PMID- 24908504
TI  - Iron sensors and signals in response to iron deficiency.
AB  - The transcription of genes involved in iron acquisition in plants is induced
      under iron deficiency, but our understanding of iron sensors and signals remains
      limited. Iron Deficiency-responsive Element-binding Factor 1 (IDEF1) and
      Hemerythrin motif-containing Really Interesting New Gene- and Zinc-finger
      proteins (HRZs)/BRUTUS (BTS) have recently emerged as candidate iron sensors
      because of their functions as potent regulators of iron deficiency responses and
      their iron-binding properties. IDEF1 is a central transcriptional regulator of
      graminaceous genes involved in iron uptake and utilization, predominantly during
      the early stages of iron deficiency. HRZs/BTS are E3 ubiquitin ligases and
      negative regulators of iron deficiency responses in both graminaceous and non
      graminaceous plants. Rice OsHRZ1 and OsHRZ2 are also potent regulators of iron
      accumulation. Characterizing these putative iron sensors also provides clues to
      understanding the nature of iron signals, which may involve ionized iron itself,
      other metals, oxygen, redox status, heme and iron-sulfur clusters, in addition to
      metabolites affected by iron deficiency. Systemic iron responses may also be
      regulated by phloem-mobile iron and its chelators such as nicotianamine. Iron
      sensors and signals will be identified by demonstration of signal transmission by
      IDEF1, HRZs/BTS, or unknown factors. 

PMID- 24908505
TI  - Organ accumulation and subcellular location of Cicer arietinum ST1 protein.
AB  - The ST (ShooT Specific) proteins are a new family of proteins characterized by a
      signal peptide, tandem repeats of 25/26 amino acids, and a domain of unknown
      function (DUF2775), whose presence is limited to a few families of dicotyledonous
      plants, mainly Fabaceae and Asteraceae. Their function remains unknown, although
      involvement in plant growth, fruit morphogenesis or in biotic and abiotic
      interactions have been suggested. This work is focused on ST1, a Cicer arietinum
      ST protein. We established the protein accumulation in different tissues and
      organs of chickpea seedlings and plants and its subcellular localization, which
      could indicate the possible function of ST1. The raising of specific antibodies
      against ST1 protein revealed that its accumulation in epicotyls and radicles was
      related to their elongation rate. Its pattern of tissue location in cotyledons
      during seed formation and early seed germination, as well as its localization in
      the perivascular fibres of epicotyls and radicles, indicated a possible
      involvement in seed germination and seedling growth. ST1 protein appears both
      inside the cell and in the cell wall. This double subcellular localization was
      found in every organ in which the ST1 protein was detected: seeds, cotyledons and
      seedling epicotyls and radicles. 

PMID- 24908506
TI  - Plant COP9 signalosome subunit 5, CSN5.
AB  - CSN5 is a subunit of the COP9 signalosome (CSN) and carries the metallo-protease
      catalytic center for the complex. This highly conserved gene has been a subject
      of intense research in part because human Csn5 (Jab1) has been tightly linked to
      cancer. We briefly summarize recent research advances on the structure and
      mechanisms of the CSN in general, and then focus on the Arabidopsis CSN5 genes
      and their products, AtCSN5A and AtCSN5B. We also briefly discuss CSN6 genes,
      which are closely related share many similarities to CSN5. CSN5 and CSN6 genes
      are duplicated in mustard family of plants as well as in several plant species
      that have no phylogenetic correlation. Sequence homology comparison further
      suggests that at least some of the duplication events occurred independently. We
      review and analyze the phenotypic and expression differences of the two CSN5
      genes in Arabidopsis, and suggest that they play overlapping as well as
      specialized roles in plant development. Arabidopsis CSN5 protein sequences are
      more similar to those of complex organisms such as humans than to yeasts and
      unicellular alga, suggesting that the structure and mechanism of Arabidopsis CSN5
      likely resembles more to those of human than to yeast. We argue that possession
      of two different isoforms of CSN5s gives Arabidopsis a unique advantage as a
      genetic model of CSN5 to dissect the multifaceted functions and mechanistic
      versatilities of this important cellular regulator. 

PMID- 24908507
TI  - Phenolic characterization and variability in leaves, stems and roots of Micro-Tom
      and patio tomatoes, in response to nitrogen limitation.
AB  - Phenolics are implicated in the defence strategies of many plant species
      rendering their concentration increase of putative practical interest in the
      field of crop protection. Little attention has been given to the nature,
      concentration and distribution of phenolics within vegetative organs of tomato
      (Solanum lycopersicum. L) as compared to fruits. In this study, we extensively
      characterized the phenolics in leaves, stems and roots of nine tomato cultivars
      using high-performance liquid chromatography coupled to electrospray ionization
      tandem mass spectrometry (LC-MS(n)) and assessed the impact of low nitrogen (LN)
      availability on their accumulation. Thirty-one phenolics from the four sub
      classes, hydroxycinnamoyl esters, flavonoids, anthocyanins and phenolamides were
      identified, five of which had not previously been reported in these tomato
      organs. A higher diversity and concentration of phenolics was found in leaves
      than in stems and roots. The qualitative distribution of these compounds between
      plant organs was similar for the nine cultivars with the exception of Micro-Tom
      because of its significantly higher phenolic concentrations in leaves and stems
      as compared to roots. With few exceptions, the influence of the LN treatment on
      the three organs of all cultivars was to increase the concentrations of
      hydroxycinnamoyl esters, flavonoids and anthocyanins and to decrease those of
      phenolamides. This impact of LN was greater in roots than in leaves and stems.
      Nitrogen nutrition thus appears as a means of modulating the concentration and
      composition of organ phenolics and their distribution within the whole plant. 

PMID- 24908508
TI  - Differential expression of structural genes for the late phase of phytic acid
      biosynthesis in developing seeds of wheat (Triticum aestivum L.).
AB  - In cereals, phytic acid (PA) or inositol hexakisphosphate (IP6) is a well-known
      phosphate storage compound as well as major chelator of important micronutrients
      (iron, zinc, calcium, etc.). Genes involved in the late phases of PA biosynthesis
      pathway are known in crops like maize, soybeans and barley but none have been
      reported from wheat. Our in silico analysis identified six wheat genes that might
      be involved in the biosynthesis of inositol phosphates. Four of the genes were
      inositol tetraphosphate kinases (TaITPK1, TaITPK2, TaITPK3, and TaITPK4), and the
      other two genes encode for inositol triphosphate kinase (TaIPK2) and inositol
      pentakisphosphate kinase (TaIPK1). Additionally, we identified a homolog of Zmlpa
      1, an ABCC subclass multidrug resistance-associated transporter protein (TaMRP3)
      that is putatively involved in PA transport. Analyses of the mRNA expression
      levels of these seven genes showed that they are differentially expressed during
      seed development, and that some are preferentially expressed in aleurone tissue.
      These results suggest selective roles during PA biosynthesis, and that both lipid
      independent and -dependent pathways are active in developing wheat grains. TaIPK1
      and TaMRP3 were able to complement the yeast ScDeltaipk1 and ScDeltaycf1 mutants,
      respectively, providing evidence that the wheat genes have the expected
      biochemical functions. This is the first comprehensive study of the wheat genes
      involved in the late phase of PA biosynthesis. Knowledge generated from these
      studies could be utilized to develop strategies for generating low phyate wheat. 

PMID- 24908509
TI  - Phytoalexin biosynthesis genes are regulated and involved in plant response to
      Ralstonia solanacearum infection.
AB  - Genes encoding phytoalexin biosynthesis enzymes are transcriptionally regulated
      and are required for defense against fungi and oomycetes. Here, we studied the
      regulation of tobacco 5-epi-aristolochene synthase 4 (EAS4) promoters on
      bacterial infection and investigated the roles of tomato and Arabidopsis
      phytoalexin biosynthesis genes in defense against pathogenic bacteria. Our
      results showed that the Nicotiana glutinosa EAS4 (NgEAS4) promoter was
      significantly induced by treatments with several bacteria in treated and systemic
      leaves of transgenic plants. This promoter was also partially induced by
      treatments with type-III secretion-deficient mutants and total lysate of R.
      solanacearum (Rs), revealing that both bacterial pathogen-associated molecular
      patterns (PAMPs) and effectors are involved in R. solanacearum-induced local and
      systemic activation of the NgEAS4 promoter. Furthermore, the absence of a cis
      element GT-1 box in the NgEAS4 promoter abolished systemic activation in non
      treated leaves, whereas disruption of the GT-1 box of the N. tabacum EAS4
      (NtEAS4) promoter led to constitutive expression. Moreover, silencing of tomato
      sesquiterpene synthase genes and disruption of the key gene PAD3 for Arabidopsis
      camalexin biosynthesis resulted in decreased tolerance to R. solanacearum. These
      results together, reveal the varied function of GT-1 boxes in regulating tobacco
      EAS4 promoters and the involvement of phytoalexin-biosythesis genes in plant
      defense against R. solanacearum. 

PMID- 24908510
TI  - Functional characterization of Synechococcus amylosucrase and fructokinase
      encoding genes discovers two novel actors on the stage of cyanobacterial sucrose
      metabolism.
AB  - Plants and most cyanobacteria metabolize sucrose (Suc) with a similar set of
      enzymes. In Synechococcus sp. PCC 7002, a marine cyanobacterium strain, genes
      involved in Suc synthesis (spsA and sppA) have been characterized; however, its
      breakdown was still unknown. Indeed, neither invertase nor sucrose synthase
      genes, usually found in plants and cyanobacteria, were found in that
      Synechococcus genome. In the present study, we functionally characterized the
      amsA gene that codes for an amylosucrase (AMS), a glycoside-hydrolase family 13
      enzyme described in bacteria, which may catabolyze Suc in Synechococcus.
      Additionally, we identified and characterized the frkA gene that codes for a
      fructokinase (FRK), enzyme that yields fructose-6P, one of the substrates for Suc
      synthesis. Interestingly, we demonstrate that spsA, sppA, frkA and amsA are
      grouped in a transcriptional unit that were named Suc cluster, whose expression
      is increased in response to a salt treatment. This is the first report on the
      characterization of an AMS and FRK in an oxygenic photosynthetic microorganism,
      which could be associated with Suc metabolism. 

PMID- 24908511
TI  - Rice RCN1/OsABCG5 mutation alters accumulation of essential and nonessential
      minerals and causes a high Na/K ratio, resulting in a salt-sensitive phenotype.
AB  - Mineral balance and salt stress are major factors affecting plant growth and
      yield. Here, we characterized the effects of rice (Oryza sativa L.) reduced culm
      number1 (rcn1), encoding a G subfamily ABC transporter (OsABCG5) involved in
      accumulation of essential and nonessential minerals, the Na/K ratio, and salt
      tolerance. Reduced potassium and elevated sodium in field-grown plants were
      evident in rcn1 compared to original line 'Shiokari' and four independent rcn
      mutants, rcn2, rcn4, rcn5 and rcn6. A high Na/K ratio was evident in the shoots
      and roots of rcn1 under K starvation and salt stress in hydroponically cultured
      plants. Downregulation of SKC1/OsHKT1;5 in rcn1 shoots under salt stress
      demonstrated that normal function of RCN1/OsABCG5 is essential for upregulation
      of SKC1/OsHKT1;5 under salt stress. The accumulation of various minerals in
      shoots and roots was also altered in the rcn1 mutant compared to 'Shiokari' under
      control conditions, potassium starvation, and salt and d-sorbitol treatments. The
      rcn1 mutation resulted in a salt-sensitive phenotype. We concluded that
      RCN1/OsABCG5 is a salt tolerance factor that acts via Na/K homeostasis, at least
      partly by regulation of SKC1/OsHKT1;5 in shoots. 

PMID- 24908512
TI  - Iron around the clock.
AB  - Carbon assimilation, a key determinant of plant biomass production, is under
      circadian regulation. Light and temperature are major inputs of the plant clock
      that control various daily rhythms. Such rhythms confer adaptive advantages to
      the organisms by adjusting their metabolism in anticipation of environmental
      fluctuations. The relationship between the circadian clock and nutrition extends
      far beyond the regulation of carbon assimilation as mineral nutrition, and
      specially iron homeostasis, is regulated through this mechanism. Conversely, iron
      status was identified as a new and important input regulating the central
      oscillator, raising the question of the nature of the Fe-dependent signal that
      modulates the period of the circadian clock. Several lines of evidence strongly
      suggest that fully developed and functional chloroplasts as well as early light
      signalling events, involving phytochromes, are essential to couple the clock to
      Fe responses. Nevertheless, the exact nature of the signal, which most probably
      involves unknown or not yet fully characterized elements of the chloroplast-to
      nucleus retrograde signalling pathway, remains to be identified. Finally, this
      regulation may also involves epigenetic components. 

PMID- 24908513
TI  - Proteomic analysis of 'Zaosu' pear (Pyrus bretschneideri Rehd.) and its early
      maturing bud sport.
AB  - Maturation of fruits involves a series of physiological, biochemical, and
      organoleptic changes that eventually make fleshy fruits attractive, palatable,
      and nutritional. In order to understand the mature mechanism of the early
      maturing bud sport of 'Zaosu' pear, we analyzed the differences of proteome
      expression between the both pears in different mature stages by the methods of a
      combination of two-dimensional electrophoresis (2-DE) and matrix assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis.
      Seventy-five differential expressed protein spots (p<0.05) were obtained between
      'Zaosu' pear and its early-maturing bud sport, but only sixty-eight were
      demonstratively identified in the database of NCBI and uniprot. The majority of
      proteins were linked to metabolism, energy, stress response/defense and cell
      structure. Additionally, our data confirmed an increase of proteins related to
      cell-wall modification, oxidative stress and pentose phosphate metabolism and a
      decrease of proteins related to photosynthesis and glycolysis during the
      development process of both pears, but all these proteins increased or decreased
      faster in the early-maturing bud sport. This comparative analysis between both
      pears showed that these proteins were closely associated with maturation and
      could provide more detailed characteristics of the maturation process of both
      pears. 

PMID- 24908514
TI  - Purification and identification of a nuclease activity in embryo axes from French
      bean.
AB  - Plant nucleases are involved in nucleic acid degradation associated to programmed
      cell death processes as well as in DNA restriction, repair and recombination
      processes. However, the knowledge about the function of plant nucleases is
      limited. A major nuclease activity was detected by in-gel assay with whole
      embryonic axes of common bean by using ssDNA or RNA as substrate, whereas this
      activity was minimal in cotyledons. The enzyme has been purified to
      electrophoretic homogeneity from embryonic axes. The main biochemical properties
      of the purified enzyme indicate that it belongs to the S1/P1 family of nucleases.
      This was corroborated when this protein, after SDS-electrophoresis, was excised
      from the gel and further analysis by MALDI TOF/TOF allowed identification of the
      gene (PVN1) that codes this protein. The gene that codes the purified protein was
      identified. The expression of PVN1 gene was induced at the specific moment of
      radicle protrusion. The inclusion of inorganic phosphate to the imbibition media
      reduced the level of expression of this gene and the nuclease activity suggesting
      a relationship with the phosphorous status in French bean seedlings. 

PMID- 24908515
TI  - Acetohydroxyacid synthase activity and transcripts profiling reveal tissue
      specific regulation of ahas genes in sunflower.
AB  - Acetohydroxyacid synthase (AHAS) is the target site of several herbicides and
      catalyses the first step in the biosynthesis of branched chain amino acid. Three
      genes coding for AHAS catalytic subunit (ahas1, ahas2 and ahas3) have been
      reported for sunflower. The aim of this work was to study the expression pattern
      of ahas genes family and AHAS activity in sunflower (Helianthus annuus L.).
      Different organs (leaves, hypocotyls, roots, flowers and embryos) were evaluated
      at several developmental stages. The transcriptional profile was studied through
      RT-qPCR. The highest expression for ahas1 was shown in leaves, where all the
      induced and natural gene mutations conferring herbicide resistance were found.
      The maximal expression of ahas2 and ahas3 occurred in immature flowers and
      embryos. The highest AHAS activity was found in leaves and immature embryos.
      Correlation analysis among ahas gene expression and AHAS activity was discussed.
      Our results show that differences in ahas genes expression are tissue-specific
      and temporally regulated. Moreover, the conservation of multiple AHAS isoforms in
      sunflower seems to result from different expression requirements controlled by
      tissue-specific regulatory mechanisms at different developmental stages. 

PMID- 24908516
TI  - Real time observation system for monitoring environmental impact on marine
      ecosystems from oil drilling operations.
AB  - Environmental awareness and technological advances has spurred development of new
      monitoring solutions for the petroleum industry. This paper presents experience
      from a monitoring program off Norway. To maintain operation within the limits of
      the government regulations Statoil tested a new monitoring concept. Multisensory
      data were cabled to surface buoys and transmitted to land via wireless
      communication. The system collected information about distribution of the
      drilling wastes and the welfare of the corals in relation to threshold values.
      The project experienced a series of failures, but the backup monitoring provided
      information to fulfil the requirements of the permit. The experience demonstrated
      the need for real time monitoring and how such systems enhance understanding of
      impacts on marine organisms. Also, drilling operations may improve by taking
      environmental information into account. The paper proposes to standardize and
      streamline monitoring protocols to maintain comparability during all phases of
      the operation and between drill sites. 

PMID- 24908517
TI  - n-3 LCPUFA improves cognition: the young, the old and the sick.
AB  - Due to the implication of docosahexaenoic acid (DHA) in neurogenesis,
      synaptogenesis, neurite outgrowth and to its high incorporation into the brain,
      this n-3 long chain polyunsaturated fatty acid (LCPUFA) is considered as crucial
      in the development and maintenance of the learning memory performance throughout
      life. In the present chapter we aimed at reviewing data investigating the
      relation between DHA and cognition during the perinatal period, young adult- and
      adulthood and neurodegenerative diseases such as Alzheimer disease (AD). In
      Humans, dietary DHA supplementation from the perinatal period to adulthood does
      not reveal a clear and consistent memory improvement whereas it is the case in
      animal studies. The positive effects observed in animal models may have been
      enhanced by using n-3 PUFA deficient animal models as controls. In animal models
      of AD, a general consensus on the beneficial effects of n-3 LCPUFA in attenuating
      cognitive impairment was established. These studies make DHA a potential suitable
      micronutrient for the maintenance of cognitive performance at all periods of
      life. 

PMID- 24908518
TI  - The effect of material hardship on child protective service involvement.
AB  - This study employs four waves of survey data on 1,135 families from the Illinois
      Families Study, a longitudinal panel study of Temporary Assistance for Needy
      Families in Illinois. This study explores the following issues within this low
      income population: (1) whether material hardships are associated with child
      protective services (CPS) investigations, (2) whether the effect of material
      hardship on CPS differs by the type of child maltreatment investigated, and (3)
      whether psychological distress mediates the association between material hardship
      and CPS involvement. Results from pooled and fixed effects logistic regressions
      suggest that caregivers who experience material hardship are more likely to
      become involved in CPS. In general, investigated neglect reports are responsive
      to particular types of hardship such as housing and food, while investigated
      physical abuse reports are responsive to levels of hardship regardless of
      specific types. The association between material hardship and CPS involvement is
      not fully explained by depressive symptoms or parenting stress. The study results
      suggest that in order to prevent child maltreatment, it may be necessary to
      address a family's unmet material needs through economic support interventions.

PMID- 24908519
TI  - Huntington's Disease presenting with chorea of the ears.

PMID- 24908521
TI  - Intended location of future career practice among graduating medical students:
      perspective from social cognitive career theory in Nepal.
AB  - BACKGROUND: Medical workforce shortages and mal-distributions world-wide make
      understanding how, where and what our future doctors wish to practice is
      increasingly important. Understanding of factors such as available
      infrastructure, provision of incentives and many others influences the decisions
      of doctors to leave or to stay. Therefore the strategies effective for retention,
      is imperative in conducting the study based on a sound theoretical framework in
      predicting future medical workforce needs. The study used the theoretical
      framework of Social Cognitive Career Theory to identify the predictors on future
      practice location. METHODS: The study was cross-sectional descriptive in design
      targeting the Nepalese medical students in the final year and doing internships
      in Nepal. Anonymous self administered questionnaire was distributed among 480
      students but 393 students were involved due to non response and incompleteness.
      Findings of the study were presented in frequency tables for univariate
      descriptive analysis and bivariate findings were presented by cross tabulation.
      RESULTS: About two thirds 259 (65.9%) of the participants had chosen within
      country location for future practice. Among those who had chosen within country
      choice, about an equal percentage of the respondents had chosen rural 131 (50.8%)
      and urban 128 (49.2%) location. Among those who had chosen within country for
      future practice location, less than one fifth of the participants had chosen
      private sector for future practice. CONCLUSIONS: Majority of the medical
      graduates wish to practice within country location. Most of which chose public
      sector for future practice. None of the SCCT construct had any significant
      association within country location.

PMID- 24908520
TI  - [Renal denervation for treating hypertension: experience at the University
      Hospital in Lyon].
AB  - AIM: We report the first experience of Lyon's university hospital regarding renal
      denervation to treat patients with resistant essential hypertension. PATIENTS AND
      METHODS: Over a one-year period, 17 patients were treated (12 men, 5 women) with
      renal denervation. Baseline characteristics were as follows: age 56.5+/-11.5
      years, BMI 33+/-5kg/m(2) and ambulatory blood pressure 157+/-16/87+/-13mmHg with
      4.2+/-1.5 anti-hypertensive treatment. RESULTS: We did not observe intra
      operative or early complications. After a median follow-up of 3 months and with
      the same anti-hypertensive treatment, office systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) decrease respectively of 20+/-15 (P<0.001) and
      10+/-13mmHg (P=0.014) (n=17). After six months of follow-up, ambulatory blood
      pressure (ABPM) decrease of 17.5+/-14.9mmHg (P=0.027) for SBP and of 10.5+/
      9.6mmHg (P=0.029) for DBP (n=6). Among these patients, five of them were
      controlled (ABPM inferior to 130/80mmHg) and electrical left ventricular
      hypertrophy indexes decreased: R wave in aVL lead of 4+/-3mm (P=0.031), Sokolow
      index of 3+/-3mm (P=0.205), Cornell voltage criterion of 9+/-7mm (P=0.027) and
      Cornell product of 1310+/-1104 (P=0.027). CONCLUSION: Our results are in
      accordance with data from other centers. On average blood pressure decreases
      significantly but important inter individual variations are observed. The
      procedure seems safe.

PMID- 24908522
TI  - Nutritional status of children in two districts of the mountain region of Nepal.
AB  - BACKGROUND: Nutritional status is a prime indicator of health. Generally, three
      anthropometric indicators are often used to assess nutritional status during
      childhood and adolescence: underweight (weight-for-age), stunting (height- for
      age) and thinness (BMI-for-age). Malnutrition in children is a major public
      health problem in many developing countries. This study was conducted to assess
      nutritional status among children attending health camps in two mountainous
      districts in Nepal. METHODS: Five hundred and seventy five children below 15
      years of age attending the medical camp in Humla and Mugu districts in October
      2011 were assessed for nutritional status. For children less than five years,
      weight for age, weight for height and height for age as per WHO classification,
      and for children between five to 15 years age specific values of height, weight
      and Body Mass Index (BMI) were calculated. RESULTS: In Humla district, 28.2%
      children were undernourished, 8.8% wasted and 22.4% stunted in less than five
      years. In the same age group, 31.7% children were undernourished, 9.4% wasted and
      29.4% stunted in Mugu district. In the age group five to 15 years, thinness was
      seen in 22.4% and 29.4% children in Humla and Mugu respectively. CONCLUSIONS:
      Malnutrition (underweight, stunting, wasting and thinness) still constitutes a
      major health problem among Nepalese children, particularly in mountainous
      regions.

PMID- 24908524
TI  - Wasp bite in a referral hospital in Nepal.
AB  - BACKGROUND: Wasp bite is an important occupational hazard in Nepal. Almost 25% of
      the victims die. This study aimed to identify the demographics, clinical
      presentation, hospital course and outcome of wasp bite victims in a referral
      hospital in Nepal. METHODS: A retrospective study was conducted in Tribhuvan
      University Teaching Hospital, Kathmandu. Medical records of patients admitted for
      wasp bite between January 2008 and December 2012 were reviewed. Demographic,
      clinical and laboratory data were collected and their effects on outcomes in the
      form of death, duration of hospitalization, number of dialysis sessions and time
      to resolution of oliguria were analyzed. RESULTS: All 18 patients came from rural
      areas, 13 (72%) were farmers, mean age was 39.6 +/-16.7 years (range 7 to 69).
      Most bites occurred between August and November. Oliguria, vomiting, red urine
      and jaundice were the main presenting symptoms; oliguria developed within 48
      hours of bite in 17 (94 %) cases. Nine patients (50%) required blood transfusion.
      All developed acute renal failure (ARF) and required dialysis, mean hemodialysis
      session being 7.4+/-5.3 (range 1 to 20). Sixteen patients (89 %) received steroid
      for presumed interstitial nephritis. One patient expired. Mean time to resolution
      of oliguria was 15.9+/-9.5 days (range 2 to 35). Mean hospital stay was 18.7+/
      13.4 days (range 1 to 46), those having higher number of bites had longer stay.
      CONCLUSIONS: Wasp bite mostly affects farmers of working age in rural Nepal.
      Hemolysis and acute renal failure are two important complications. Timely
      dialysis in established acute renal failure and steroid in suspects of
      interstitial nephritis improves survival.

PMID- 24908523
TI  - A randomized trial comparing skin closure in cesarean section: interrupted suture
      with nylon vs subcuticular suture with No '1' polyfilament.
AB  - BACKGROUND: Cesarean section is one of the most commonly performed operations in
      most countries of the world including Nepal. Hence there is a load on the
      financial resources of healthcare system. The rational of this study was to
      utilize the remaining No '1' polyfilament after closing rectus sheath to stitch
      skin. So, the primary objective was to determine the wound complication rates for
      subcuticular suture with No'1' petcryl (polyfilamentpolyglycolic acid) Vs
      intermittent suture with nylon 2-0 for skin closure at cesarean delivery and
      secondary objective was to compare postoperative pain and patient satisfaction
      about the scar. METHODS: One hundred and thirty eight women undergoing cesarean
      section at Chitwan Medical College was randomized to either intermittent skin
      suture with nylon 2-0 or subcuticular with polyfilament No '1' (remaining suture
      after closing rectus sheath). Evidence of wound infection, pain and overall
      satisfaction were assessed postoperatively. RESULTS: The overall wound
      complications rate in subcuticular stitch with No'1' polyfilament suture were
      similar as in intermittent mattress stitch with nylon 2-0 (15.9% vs. 14.49%).
      Pain on postoperative third day and six weeks and overall satisfaction about
      wound were similar in both groups. Only prolong rupture of membrane >18 hours was
      found to be a significant risk factor of wound infection (OR: 3.4; p=0.04).
      CONCLUSIONS: The remaining no '1' polyfilament suture (petcryl) after suturing
      rectus sheath can be safely used to close skin suture in cesarean section.

PMID- 24908525
TI  - Household passive smoking and acute respiratory infection among under-five
      children attending Kanti Children's Hospital.
AB  - BACKGROUND: Worldwide, children are more heavily exposed to passive smoking than
      any other age group where majority of these occur in child's house.Children's
      passive smoking and risk of developing respiratory diseases has been well
      established in several studies. However, such studies are limited in Nepal.
      Therefore, the objective of this study was to determine association between
      household passive smoking and acute respiratory infection among under- five
      children attending Kanti Children's Hospital. METHODS: A descriptive, cross
      sectional study using quantitative method was carried out in Kanti Children's
      Hospital. Data was collected by face-to-face interview from 198 parents.Bivariate
      and multivariate analyses were performed to see association between household
      passive smoking and acute respiratory infection. RESULTS: Among 198 children,
      79(39.9%)were passive smokers. Among the total passive smokers, 31(39.2%) were
      exposed to paternal smoking, 18(22.8%) to parental smoking, 18(22.8%) to other
      member's smoking and 12(15.2%) to maternal smoking. Among 36 daily passive
      smokers, 18(50.0%) were exposed to high amount and 18(50.0%) to low amount of
      passive smoking. Household passive smoking had a slight risk of developing acute
      respiratory infection where adjusted odds ratio was 1.35;however it was not
      statistically significant. CONCLUSIONS: Children exposed to passive smoking had a
      slight risk of developing acute respiratory infection than non-passive smokers
      however, it was not statistically significant.

PMID- 24908526
TI  - Examining stratified cesarean section rates using Robson classification system at
      Tribhuvan University Teaching Hospital.
AB  - BACKGROUND: Caesarean section rates have been increasing worldwide over the past
      few decades, with most countries and regions exceeding the World Health
      Organization recommended rate of 15% of all deliveries. METHODS: This study was
      carried out with the objective of reviewing the rates of cesarean sections over
      five years (2005-2010) and to assess the stratified rates of cesarean sections
      for audit of intrapartum management in University Teaching Hospital, Institute of
      Medicine. Data was stratified into 10 mutually exclusive groups, by using the
      method presented by Michael Robson. RESULTS: A total of 5907 women had under gone
      caeserean section over a period of five years. The results showed a growing trend
      of cesarean section rate from 16.6% to 25.4%. The results of this analysis using
      the Robson classification has shown that group 1(Nulliparous, single cephalic >=
      37 weeks gestation in spontaneous labour) has the largest number of cesarean
      deliveries followed by group 3(Multiparous, single cephalic >=37 weeks gestation
      in spontaneous labor, no previous CS), although Robson classification showed that
      group 5 was the biggest contributor. CONCLUSIONS: The growing and uniform
      distribution (throughout the year) of cesarean section has been observed for five
      years. This analysis provides evidence-based data so we can analyze where to aim
      our preventive measures and focus efforts in reducing the rate of CS. We would
      like to suggest that all hospitals and health authorities apply this standardized
      classification system as to monitor their CS rates and find ways to reduce it,
      and improve quality care.

PMID- 24908527
TI  - Knowledge of diabetes mellitus among pregnant women in three districts of Nepal.
AB  - BACKGROUND: Diabetes mellitus is an emerging health problem in developing world
      with the consumption of energy dense diet and inactive lifestyle. The problem of
      diabetes is further expanded due to ignorance and lack of knowledge. The aim of
      the study was to assess the knowledge of diabetes among pregnant women in three
      districts of Nepal. METHODS: A community based cross-sectional study was
      conducted in three districts in mountain, hilly and plain areas of Nepal. A total
      of 590 pregnant women were interviewed during the period of July 2009 to June
      2010. A knowledge score system was applied. Poor score was <40%, average (40-60%)
      and good (>60%) of the total score. Statistical software SPSS 11.5 was used for
      data entry, data management and analysis. RESULTS: Out of 590 pregnant women,
      only 41% had heard about diabetes mellitus. Majority of the participants (75%)
      from age group >30 years had not heard about diabetes. Among the 241 with some
      knowledge, the knowledge score median percent(range) on the meaning, symptoms,
      risk factors, treatment, prevention, complications and overall knowledge were
      50%(0-100), 25% (0-75), 20% (0-60), 20% (0-100), 25% (0-100), 20% (0-60) and 26%
      (0- 58) respectively. According to defined category, majority of those who ever
      heard about diabetes had poor knowledge (95%). Knowledge among literate women
      (p=.001), women residing in Kailali district (plain region) (p=.003) and those
      with positive family history of diabetes (p=.003) was found to be significant.
      CONCLUSIONS: As large proportions of Nepalese pregnant women do not have any
      knowledge or have poor knowledge regarding diabetes, extensive health education
      and health promotion programs are urgently recommended to prevent diabetes in
      Nepal.

PMID- 24908528
TI  - Community attitudes towards leprosy affected persons in Pokhara municipality of
      western Nepal.
AB  - BACKGROUND: Stigma is a social process of interpretation of an attribute. Leprosy
      has been seen as the epitome of stigmatization. The psychosocial impact a person
      has to bear in a society after the diagnosis weighs heavier than the physical
      afflictions it causes, which does not get cured with the mere medical treatment.
      There are various factors which construct the perception of stigma in both
      leprosy affected persons and unaffected persons. The main purpose of this study
      was to determine the level of perceived stigma and the risk factors contributing
      to it among community people living in ward 15, Pokhara municipality. METHODS:
      Cross-sectional descriptive study among 281 community people above the age of 18
      years was conducted. Two sets of questionnaire form with additional Explanatory
      Model Interview Catalogue (EMIC) for each individual were used. RESULTS: Among
      281 community people, the median score of perceived stigma was 12 while it ranged
      from 0-30. Ethnic groups, Brahmins, Dalits and minorities had highest perceived
      stigma score of 15 and above compared to the rest (p=0.001), community people
      living at the distance more than 2 km had highest perceived stigma score of 15
      compared to those living closer to the hospital (p=0.019) and nuclear family had
      highest perceived stigma score of 15 compared to the joint family (p=0.014).
      People who lacked information on leprosy had higher score of perceived stigma
      compared to those who had information on leprosy (p=0.002).Similarly, those who
      perceived leprosy to be difficult to treat (p<0.001) and a severe disease
      (p<0.001) had highest score of perceived stigma. CONCLUSIONS: Stigma in leprosy
      was found highly associated with the lack of information about leprosy and their
      perception in treatment and disease severity. Stigma reduction strategies should
      focus on health education, targeting to alleviate their perception about the
      disease with their active participation.

PMID- 24908529
TI  - Fetal biophysical profile score and perinatal outcome.
AB  - BACKGROUND: Sudden fetal demise, perinatal morbidity and mortality are still some
      of the major obstetrical challenges. Reduced fetal movements may have some
      bearing to fetal asphyxia and death, so timely detection of such condition and
      measures taken can prevent such mishaps. METHODS: A descriptive prospective study
      was conducted at Tribhuvan University Teaching Hospital, Department of Obstetrics
      and Gynecology from January to December 2002 in 55 cases to find out the
      relationship of Biophysical Profile Score with perinatal outcome in pregnant
      mothers with decreased fetal movement counts at or above 34 weeks of gestational
      age. The mode of delivery, Apgar score, neonatal admission and perinatal
      mortality were analyzed. RESULTS: The study demonstrated that most of the fetuses
      were in good condition with 87% of the cases scoring 8-10 BPS (normal), 6%
      scoring six (equivocal) and only 7% got four score (abnormal). Having the
      abnormal BPS of four significantly increased the risk of perinatal mortality by
      50% (p=0.000). This study could not detect any significant association between
      Apgar score and neonatal morbidities, but showed significant correlation between
      BPS and caesarean section. The patients having lower BPS tended to undergo more
      caesarean section delivery than patients having normal BPS (p=0.009).
      CONCLUSIONS: An abnormal BPS of four in cases of reduced fetal movement counts
      significantly influenced the risk of perinatal death. However reduced fetal
      movements only did not raise the risk of fetal morbidity and mortality. So BPS
      should be beneficial to detect the fetuses at risk in the patients having less
      fetal movements for the proper management at right time.

PMID- 24908530
TI  - Spectrum of hematological malignancies and peripheral cytopenias.
AB  - BACKGROUND: Peripheral cytopenias such as anemia, thrombocytopenia, bicytopenia
      and pancytopenia are common peripheral blood findings in hematological
      malignances for which bone marrow evaluation is often required. The study was
      conducted to identify the spectrum of hematological malignancies in association
      with peripheral cytopenia. METHODS: One year retrospective study was conducted in
      Tribhuvan University Teaching Hospital. Data of bone marrow examination were
      retrieved from the archives of the hematology department and analyzed. RESULTS:
      Total number of hematological malignancies out of 400 cases of bone marrow
      examination was 86 (21.5%). Median age was 13 years. 48 (55.81 %) were children.
      Male: female ratio was 1.26:1. Frequency of bicytopenia, pancytopenia, anemia and
      thrombocytopenia were 34.88%, 23.25%, 23.25% and 9.3% respectively. Commonest
      hematological malignancy was acute leukemia (70.73%) followed by chronic myeloid
      leukemia (6.97%), plasma cell neoplasm (8.13%), myelodysplastic syndrome (4.65%),
      Non-Hodgkin lymphoma (2.32%) and hypereosinophilic syndrome (1.16%). In cases of
      acute leukemia 27 presented with bicytopenia, 15 each with pancytopenia and
      anemia; and seven with thrombocytopenia. Number cases presenting with bicytopenia
      and pancytopenia in multiple myeloma was one each and with anemia two.
      Thrombocytopenia was seen in monoclonal gammopathy of undetermined significance.
      Bicytopenia and pancytopenia were seen in two cases each of myelodysplastic
      syndrome. Chronic myeloid leukemia and non-Hodgkin lymphoma showed anemia and
      pancytopenia respectively. CONCLUSIONS: More than 90% of hematological
      malignancies presented with cytopenia. Bicytopenia and pancytopenia together
      constituted 58%. 97% of acute leukemia presented with cytopenia and majority of
      them had pancytopenia or bicytopenia.

PMID- 24908531
TI  - Experience sharing of retroperitoneal laparoscopic ureterolithotomy from a
      teaching hospital.
AB  - BACKGROUND: Retro-peritoneal ureterolithotomy may be first option in impacted
      large upper and mid ureteric stones in selected cases. METHODS: We performed 16
      retroperitoneal laparoscopic ureterolithotomy in a teaching hospital. Out of 16
      cases, eleven stones were located in the upper ureter and rest in mid ureter.
      Main indication was impacted large stone (1.5- 2cm) (1.72 cm, mean size). Failed
      extracorporeal shock wave lithotripsy and Uretero-renoscopy were other two
      indications. Failed PCNL for renal pelvic stone were resorted to open procedure
      not RUL. RESULTS: Total 16 RUL were performed. Hospital stay in range was 3-11
      days. The mean operative time was 96 minutes and mean blood loss was 30 ml. There
      were 4 failures. No major complications were encountered. Prolong urinary leakage
      was seen in one patient. Follow up Intravenous urogram at 3 months revealed
      normal ureter in all cases. CONCLUSIONS: RUL is a good option in lieu of open
      surgery for selected patient with large hard impacted ureteral stone which are
      likely to resist any endo-urological procedure. Our experience represents a safe
      and effective treatment option as a first option for large impacted stone or as a
      salvage second option for failed endo-urological procedure or ESWL.

PMID- 24908532
TI  - Self-esteem and stress coping among proficiency certificate level nursing
      students in nursing campus Maharajgunj and Lalitpur Nursing Campus.
AB  - BACKGROUND: Nursing requires high self-esteem and effective coping strategies for
      the quality of health services that they deliver. Self -esteem and stress coping
      mechanism developed during education period is foundation for professional
      practice. So, this study was conducted to identify self-esteem, coping
      activities, and their relationship. METHODS: Descriptive cross sectional study
      was conducted among 287 PCL nursing students currently studying in different
      level in nursing campuses of the Institute of Medicine during June and July 2013.
      Self administered semi structured questionnaire and rating scales were used for
      the data collection. RESULTS: Findings showed that 21 (7.31%), 194 (67.5%), and
      67 (23.34%), students had have very high, high and moderate, self-esteem and only
      five (1.74%) have low self-esteem.The difference in self-esteem level was
      insignificant with the level of the students. Students most frequently used
      problem focused (3.36+/-0.54) followed by emotion focused (3.04+/-0.45) and
      avoidance coping activities (2.91+/-0.63). The relationship of use of coping
      activities and level of students was statistically insignificant. Self-esteem
      level had positive relation with problem focused and emotion focused coping
      activities (Pearson r: 0.114 and 0.118), though the correlation was significant
      with emotion focused coping activities only. Bicytopenia and pancytopenia were
      seen in two cases each of myelodysplastic syndrome. Chronic myeloid leukemia and
      Non-Hodgkin lymphoma showed anemia and pancytopenia respectively. CONCLUSIONS:
      Majority of PCL nursing students have high level of self-esteem. They used
      problem focused coping activities most however, use of it decreased with
      increased level of students. Students with high self -esteem used problem focused
      followed by emotion focused coping activities. Students should be encouraged to
      use problem focused coping activities.

PMID- 24908533
TI  - HLA antigen distribution in renal transplant recipients and donors.
AB  - BACKGROUND: HLA typing analysis is important in renal transplant patient. This
      study is the first report from Nepal to find out distribution of HLA A, B, DR
      antigen in live related renal transplant recipients and donors from Nepal. The
      aim of this study was to investigate the distribution of HLA in the live related
      renal transplant recipients and donors of Nepal. METHODS: In a retrospective
      study, HLA patterns were defined in 100 live related renal transplant recipients
      and donors. One year study is done from June 2011 to May 2012. The study was done
      by using sequence specific oligonucleotides primers and polymerase chain reaction
      and assay. Allele frequencies were obtained by direct counting. RESULTS: A total
      of 12 HLA-A, 15 HLA-B and 13 HLA-DRB1 alleles were identified at the four-digit
      level in the live related renal transplant recipients and donors of Nepal. High
      frequency alleles were HLA-A*11 (34.5%), A*24 (17%), A*33 (13%); HLA-B*15(27%),
      B*35(19%), B*40 (10%); HLA-DRB1*15 (33.5%), DRB1*12 (21.4%) and DRB1*04 (7.32%).
      CONCLUSIONS: These results showed considerable heterogeneity in both HLA class I
      and class II antigens. To reduce the risk of allograft rejection, transplantation
      from HLA matched donors is recommended.

PMID- 24908534
TI  - Mucopolysaccharidosis type II with inguinal hernia.
AB  - Mucopolysaccharidosis Type II (Hunter syndrome) is a rare X-linked recessive
      storage disorder caused by deficiency of lysosomal enzyme iduronate-2-sulfatase,
      causing excess accumulation of glycosaminoglycans in the lysosomes resulting in
      cellular damage, organ failure and death. Severe subtype develops characteristic
      clinical features and cognitive impairment early and die in second decade of
      life. In a resource poor setting, we report a case of Hunter syndrome, severe
      subtype, based on global development delay, coarse facies, short stature,
      hepatosplenomegaly and dysostosis multiplex on X-ray with unusual large
      congenital inguinal hernia. The diagnosis was important because of risk of
      recurrence of hernia after repair.

PMID- 24908535
TI  - A rare form of Cushing's syndrome in a 10 year old child.
AB  - Adrenocortical carcinoma as a cause of Cushing's syndrome in a child is a rare
      occurrence. Functioning adrenal carcinomas are detected usually when they are
      small while non-functioning tumors are incidentally detected when they grow to a
      large size. Here we report a case of Cushing's syndrome due to large functioning
      adrenal carcinoma(>12 cm in size) in a 10 year old female child who presented
      with clinical features of Cushing's syndrome along with virilisation.A
      combination of biochemical laboratory reports along with radiological
      investigations followed by histopathology helped us to arrive at a proper
      diagnosis. The tumor was ressected and the patient showed clinical signs of
      improvement. However, the surgical margin showed invasion by the tumor making a
      likely possibility of recurrence in the near future.

PMID- 24908536
TI  - Oral and dental complications of head and neck radiotherapy and their management.
AB  - Cancer patients who are diagnosed early and or receive effective anti tumour
      therapy can expect to live for many years after treatment and therefore
      preservation of normal tissue function is crucial to ensure long term quality of
      life. Oral complications affect hundred per cent of patients who receive
      radiotherapy to fields involving the oral cavity and combined modality treatment
      with chemotherapy may compound these effects. Oral cavity is highly susceptible
      to side effects as radiotherapy targets cells that divide rapidly and the cells
      of the mucosal lining of the mouth are rapidly dividing cells and they are thus
      injured. All patients who are to receive radiotherapy to the head and neck region
      should be sent for a dental consultation prior to the initiation of their
      treatment in order to decrease the acute and chronic post treatment sequelae.
      KEYWORDS: Dental management;head and neck cancers;radiotherapy.

PMID- 24908537
TI  - Review on Panton Valentine leukocidin toxin carriage among Staphylococcus aureus.
AB  - Panton Valentine leukocidin is a toxin making pores in the polymorphonuclear
      cells which is a virulence factor of some strains of Staphylococcus aureus.
      Initially it was produced by methicillin susceptible Staphylococcus aureus only.
      Later with the acquisition of mecA gene has lead it to be PVL positive
      methicillin resistant Staphylococcus aureus. Since MRSA are resistant to many
      antibiotics and further they produce a toxin the infections by PVL positive MRSA
      has become a challenge. PVL positive MRSA a virulent strain of drug resistant
      superbug MRSA that has spread around the world, has claimed many lives in UK,
      Europe, USA and Australia. Some strains of superbug attack the healthy young
      people and kill within 24 hrs. PVL positive Staphylococcus aureus has been
      reported to be associated with skin and soft tissue infections however they also
      cause invasive infections and necrotizing pneumonia. These microorganisms known
      to be community associated have spread to hospitals. Hospital acquired infection
      by such microorganisms lead to an increase in mortality hence should be
      controlled before they become prevalent in hospitals.

PMID- 24908538
TI  - Envisaging beyond community-based health insurance in Nepal.

PMID- 24908539
TI  - An (only) partially established paradigm of drug development of targeted
      therapies.

PMID- 24908541
TI  - Tomographic reconstruction of damage images in hollow cylinders using Lamb waves.
AB  - Lamb wave tomography (LWT) is a potential and efficient technique for non
      destructive tomographic reconstruction of damage images in structural components
      or materials. A two-stage inverse algorithm proposed by the authors for quickly
      reconstructing the damage images was applied to hollow cylinders. An aluminum
      hollow cylinder with an internal surface pit and a Carbon Fiber Reinforced
      Plastic (CFRP) laminated hollow cylinder with an artificial internal surface
      damage were used to validate the proposed method. The results show that the
      present method is capable of successfully reconstructing the images of the above
      damages in a larger inspection area with much less experimental data compared to
      some conventional ultrasonic tomography techniques. 

PMID- 24908540
TI  - A phase Ib study investigating the combination of everolimus and dovitinib in
      vascular endothelial growth factor refractory clear cell renal cancer.
AB  - BACKGROUND: Everolimus (mammalian target of rapmaycin (mTOR) inhibitor) and
      dovitinib (vascular endothelial growth factor (VEGF) and fibroblast growth factor
      2 (FGF-2) inhibitor) demonstrate activity in metastatic clear cell renal cancer.
      The combination of these agents has a broad spectrum of relevant activity. The
      combination is explored in this phase Ib study. METHODS: Patients with metastatic
      clear cell renal cancer who have failed VEGF targeted therapy were eligible. Up
      to four cohorts of three to six patients (3+3 design) were treated with
      escalating doses of everolimus and dovitinib. Dose-limiting toxicities (DLTs)
      were assessed to determine the maximum tolerated dose (MTD). An expansion cohort
      (n=15) was investigated to obtain additional efficacy information. Sequential
      fluorodeoxyglucose positron emission tomography (FDG-PET) was used as a surrogate
      marker of response. RESULTS: Overall 18 patients were recruited into the study.
      Fifteen patients received the MTD, which was everolimus 5mg orally (PO) once
      daily (OD) and dovitinib 200mg PO day 1-5/7. The MTD was associated with
      toxicity, which included fatigue, mucositis and diarrhoea in 73%, 53% and 53%
      (Common Toxicity Criteria (CTC) grade 1-4) of patients, respectively. Frequent
      biochemical abnormalities occurred (such as hypertriglyceridaemia in 67%). Higher
      doses of the combination were not tolerable due to grade 3 fatigue in 2/3
      patients and grade 3 nausea in 1/3 patients within 1 month of therapy. The
      response rate at the MDT was 1/15 (7%) while the progression free survival for
      the MTD was 7 months (95% confidence interval (CI) 2.2-11 months).
      Pharmacokinetic data at the MTD showed stable kinetics with time. CONCLUSION:
      Dovitinib and everolimus had modest activity, but did not meet all of the planned
      efficacy end-points. Fatigue was the dose limiting toxicity.

PMID- 24908542
TI  - Age distribution curve in psychiatric admissions inversely correlates with Life
      Satisfaction.
AB  - A strong inverse correlation was found between the age-distribution curve of
      psychiatric admissions and the U-bend Life Satisfaction curve. It may indicate
      that the peak of mental disorders at midlife reflects a less satisfactory period
      of life or, conversely, that the mental health load burdens of Life Satisfaction.

PMID- 24908543
TI  - Psychiatric comorbidity differences between women with history of childhood
      sexual abuse who are methadone-maintained former opiate addicts and non-addicts.
AB  - Following our finding of high rates of obsessive compulsive disorder (OCD) among
      methadone maintained (MMT) former opiate addict women with a history of childhood
      sexual abuse, we compared 68 MMT sexually abused women to 48 women from a Sexual
      Abuse Treatment Center (SATC) without a history of opiate addiction, for clinical
      OCD (Yale-Brown Obsessive Compulsive Scale), dissociation (Dissociative
      Experiences Scale (DES), complex-post-traumatic stress disorder (PTSD)
      (Structured Interview for Disorders of Extreme Stress - Non-Other Specify),
      sexual PTSD (the Clinician-Administered PTSD Scale) and trauma events history
      (Life Event Inventory). MMT patients were treated for longer periods and were
      older and less educated. Clinical OCD was more prevalent among the MMT patients
      (66.2% vs. 30.4%, respectively), while complex-PTSD and high dissociation score
      (DES>=30) were more prevalent among the non-addicts (46.9% vs. 19.1%, and 57.1%
      vs. 11.8% respectively). The high rate of OCD among sexually abused MMT women was
      not found in women who are sexually abused non-addicts. As dissociation was rare
      among the MMT group, it may just be that the opioids (either as street-drugs or
      as MMT) serve as an external coping mechanism when the access to the internal one
      is not possible. Future study about OCD and dissociation before entry to MMT are
      needed. 

PMID- 24908544
TI  - Syringoid Eccrine Carcinoma (SEC) of the nose: a rare and unique clinical
      condition.

PMID- 24908545
TI  - Findings of a national comparative audit of mastectomy and breast reconstruction
      surgery in England.
AB  - OBJECTIVES: This paper summarises the findings of a national audit of mastectomy
      and breast reconstruction surgery carried out in England. It describes patterns
      of treatment, and the clinical and patient-reported quality of life outcomes
      associated with these types of procedure. DESIGN: Prospective cohort study.
      SETTING: All 150 National Health Service hospital groups (NHS trusts) in England
      that provided mastectomy or breast reconstruction surgery, along with six NHS
      trusts in Wales and Scotland and 114 independent hospitals. PARTICIPANTS: Women
      aged 16 years and over undergoing mastectomy with or without immediate breast
      reconstruction, or primary delayed breast reconstruction, between 1st January
      2008 and 31st March 2009. MAIN OUTCOME MEASURES: Reconstructive utilisation, post
      operative complications and sequelae, and patient-reported satisfaction and
      quality of life. RESULTS: Overall, 21% of the 16,485 women who had mastectomy
      underwent immediate reconstruction. However, the proportion varied between
      regions from 9% to 43% (p < 0.001). Levels of patient satisfaction with
      information, choice and the quality of care were high. The proportion of women
      who experienced local complications was 10.30% (95% CI 9.78-10.84) for mastectomy
      surgery, ranged from 11.02% (9.31-12.92) to 18.24% (14.80-22.10) for different
      immediate reconstructive procedures, and from 5.00% (2.76-8.25) to 19.86% (16.21
      23.94) for types of delayed reconstruction. Breast appearance and overall well
      being scores reported 18 months after surgery were higher among women having
      immediate breast reconstruction compared to mastectomy only. Postoperative
      outcomes were similar across providers.. CONCLUSIONS: The Audit found women were
      highly satisfied with their peri-operative care, with hospital providers
      achieving similar outcomes. English providers should examine how to reduce the
      variation in rates of immediate reconstruction.

PMID- 24908546
TI  - Anatomy of the direct small branches of the proper digital nerve of the fingers:
      a cadaveric study.
AB  - BACKGROUND AND AIM: The purpose of this study was to evaluate the anatomical
      constancy of the direct small branches of the proper digital nerve. METHODS: A
      total of 208 digital nerves of the index, long, ring, and little fingers from 13
      cadavers were studied. For each digital nerve, the number of direct small
      branches was counted at the proximal and middle phalanx levels. In addition, the
      diameter of these branches was measured at the level of the branch bifurcation.
      We also measured the diameter of the proper digital nerve at the level of the
      distal interphalangeal (DIP) joint. RESULTS: The direct small branches of the
      proper digital nerve were anatomically constant among the index, long, and ring
      fingers. The average number of direct small branches was 2.7 at the proximal
      phalanx level and 2.3 at the middle phalanx level. At the level of the DIP joint,
      the average thickness of the proper digital nerve was 0.85 mm in the index
      finger, 0.84 mm in the long finger, 0.72 mm in the ring finger, and 0.49 mm in
      the little finger. CONCLUSION: In this study, we verified the anatomical
      constancy of the direct small branches of the proper digital nerve. The size of
      these branches at the proximal phalanx level was similar to that of the
      corresponding proper digital nerve at the level of the DIP joint. Therefore,
      these nerve branches at the proximal phalanx could be applied to the creation of
      various sensate flaps for the reconstruction of the fingertip injuries.

PMID- 24908547
TI  - A novel barbed suture tie-over dressing for skin grafts: a comparison with
      traditional techniques.
AB  - INTRODUCTION: Barbed suture devices have a widespread application in plastic
      surgery. The unidirectional nature of the barbs facilitates a strong grip on
      tissues and reduces the need to constantly tension the suture manually. We
      hypothesized that a barbed suture tie-over suture to secure skin grafts would be
      quicker to perform than traditional tie-overs and would also exert a greater
      downward pressure on the skin graft. METHODS: Thirty uniform areas of skin were
      excised from a cadaver. A pressure transducer was placed on the wound bed and
      covered with the excised skin along with a mineral oil-soaked wool dressing to
      act as a bolster. Three different sutures were used to secure the graft in place
      and the pressure was recorded. The tie-over techniques used were the classic silk
      tie-over, a running Vicryl RapideTM tie-over and a running barbed tie-over.
      RESULTS: The barbed tie-over exerted the most downward pressure (82.8 +/- 7.3
      mmHg) compared to the silk (46 +/- 4.85 mmHg) and the Vicryl RapideTM (18.6 +/-
      2.4 mmHg). Furthermore, the barbed tie-over was the quickest to perform (1:45 +/-
      22 s) when compared to the Vicryl RapideTM (02:57 +/- 27 s) and the silk tie
      overs (04:26 +/- 39 s). CONCLUSION: Barbed sutures are a viable option for
      securing skin grafts. They are quick to perform and provide significantly
      improved downward pressure on the skin graft. We feel that this technique would
      be especially suited to the sole operator as it can be carried out without the
      need of an assistant.

PMID- 24908548
TI  - Identification of rickettsial pathogens in ixodid ticks in northern Senegal.
AB  - The spotted fevers, caused by the Rickettsia bacteria, are a group of emerging
      diseases that are responsible for significant human morbidity. In Africa, the
      distribution of different species of Rickettsia in their tick vectors is poorly
      studied. We have collected 1169 hard ticks from 5 different species in the
      northern Senegal, close to the Saharan border. In a far northern collection site,
      corresponding to the Rickettsia africae distribution area, we collected three
      Amblyomma variegatum ticks infected by R. africae. Rickettsia africae was also
      identified in a Hyalomma marginatum rufipes tick, which may represent the
      secondary host for the pathogen. Rickettsia aeschlimannii was identified in H. m.
      rufipes, Rhipicephalus evertsi evertsi, and Hyalomma impeltatum ticks. 

PMID- 24908549
TI  - Switching STRATEGIES in HIV treatment.

PMID- 24908550
TI  - Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir
      versus continuation of non-nucleoside reverse transcriptase inhibitor with
      emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY
      NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority
      trial.
AB  - BACKGROUND: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir
      disoproxil fumarate (tenofovir) might be a safe and efficacious switch option for
      virologically suppressed patients with HIV who have neuropsychiatric side-effects
      on a non-nucleoside reverse transcriptase inhibitor (NNRTI) or who are on a
      multitablet NNRTI-containing regimen and want a regimen simplification. We
      assessed the non-inferiority of such a switch compared with continuation of an
      NNRTI-containing regimen. METHODS: STRATEGY-NNRTI is a 96 week, international,
      multicentre, randomised, open-label, phase 3b, non-inferiority trial enrolling
      adults (>=18 years) with HIV-1 and plasma HIV RNA viral load below 50 copies per
      mL for at least 6 months on an NNRTI plus emtricitabine and tenofovir regimen.
      With a computer-generated randomisation sequence, we randomly allocated
      participants (2:1; blocks of six, stratified by efavirenz use at screening) to
      switch to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir
      (switch group) or continue the NNRTI plus emtricitabine and tenofovir regimen (no
      switch group). Key eligibility criteria included no history of virological
      failure and an estimated glomerular filtration rate of 70 mL per min or greater.
      The primary endpoint was the proportion of participants with plasma viral loads
      below 50 copies per mL at week 48 based on a snapshot algorithm with a non
      inferiority margin of 12% (assessed by modified intention to treat). This trial
      is ongoing and is registered at ClinicalTrials.gov, number NCT01495702. FINDINGS:
      Between Dec 29, 2011, and Dec 13, 2012, we randomly allocated 439 participants to
      treatment: 290 participants in the switch group and 143 participants in the no
      switch group received treatment and were included in the modified intention-to
      treat population. At week 48, 271 (93%) of 290 participants in the switch group
      and 126 (88%) of 143 participants in the no-switch group maintained plasma viral
      loads below 50 copies per mL (difference 5.3%, 95% CI -0.5 to 12.0; p=0.066). We
      detected no treatment-emergent resistance in either group. Safety events leading
      to discontinuation were uncommon in both groups: six (2%) of 291 participants in
      the switch group and one (1%) of 143 in the no-switch group. INTERPRETATION:
      Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir seems to be
      efficacious and well tolerated in virologically suppressed adults with HIV and
      might be a suitable alternative for patients on an NNRTI with emtricitabine and
      tenofovir regimen considering a regimen modification or simplification. FUNDING:
      Gilead Sciences.

PMID- 24908551
TI  - Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and
      tenofovir versus continuation of ritonavir-boosted protease inhibitor with
      emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY
      PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority
      trial.
AB  - BACKGROUND: Patients with HIV on antiretroviral therapy might benefit from
      regimen simplification to reduce pill burden and dosing frequency. We aimed to
      assess the safety and efficacy of simplifying the treatment regimen for adults
      with virologically suppressed HIV infection from a ritonavir-boosted protease
      inhibitor and emtricitabine plus tenofovir disoproxil fumarate (tenofovir)
      regimen to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir.
      METHODS: STRATEGY-PI is a 96 week, international, multicentre, randomised, open
      label, phase 3b trial in which HIV-infected adults with a plasma HIV-1 RNA viral
      load of less than 50 copies per mL for at least 6 months who were taking a
      ritonavir-boosted protease inhibitor with emtricitabine plus tenofovir were
      randomly assigned (2:1) either to switch to coformulated elvitegravir,
      cobicistat, emtricitabine, and tenofovir or to continue on their existing
      regimen. Key eligibility criteria included no history of virological failure, no
      resistance to emtricitabine and tenofovir, and creatinine clearance of 70 mL/min
      or higher. Neither participants nor investigators were masked to group
      allocation. The primary endpoint was the proportion of participants with a viral
      load of less than 50 copies per mL at week 48, based on a US Food and Drug
      Administration snapshot algorithm for the modified intention-to-treat population,
      which excluded major protocol violations (prohibited resistance or not receiving
      a protease inhibitor at baseline). We prespecified non-inferiority with a 12%
      margin; if non-inferiority was established, superiority was tested as per a
      prespecified sequential testing procedure. This trial is registered at
      ClinicalTrials.gov, number NCT01475838. FINDINGS: Between Dec 12, 2011, and Dec
      20, 2012, 433 participants were randomly assigned and received at least one dose
      of study drug. Of these participants, 293 were assigned to switch to the
      simplified regimen (switch group) and 140 to remain on their existing regimen (no
      switch group); after exclusions, 290 and 139 participants, respectively, were
      analysed in the modified intention-to-treat population. At week 48, 272 (93.8%)
      of 290 participants in the switch group maintained a viral load of less than 50
      copies per mL, compared with 121 (87.1%) of 139 in the no-switch group
      (difference 6.7%, 95% CI 0.4-13.7; p=0.025). The statistical superiority of the
      simplified regimen was mainly caused by a higher proportion of participants in
      the no-switch group than in the switch group discontinuing treatment for non
      virological reasons; virological failure was rare in both groups (two [1%] of 290
      vs two [1%] of 139). We did not detect any treatment-emergent resistance in
      either group. Adverse events leading to discontinuation were rare in both groups
      (six [2%] of 293 vs four [3%] of 140). Switching to the simplified regimen was
      associated with a small, non-progressive increase from baseline in serum
      creatinine concentration. Nausea was more common in the switch group than in the
      no-switch group, but rates of diarrhoea and bloating decreased compared with
      baseline from week 4 to week 48 in the switch group, whereas there were generally
      no changes for these symptoms in the no-switch group. INTERPRETATION:
      Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir might be a
      useful regimen simplification option for virologically supressed adults with HIV
      taking a multitablet ritonavir-boosted protease inhibitor regimen. FUNDING:
      Gilead Sciences.

PMID- 24908552
TI  - Uncommon associations and catastrophic manifestation in Takayasu arteritis: an
      autopsy case report.
AB  - Takayasu arteritis, a chronic inflammatory vasculitis affecting aorta and its
      major branches, is complicated by stenosis, occlusion, and aneurysm formation.
      The aneurysm formation and subsequent complications such as heart failure, aortic
      regurgitation, and aneurysm rupture can be fatal. The aortic aneurysm rupture is
      a rare and fatal complication with only a few cases reported in the English
      literature. The involvement of coronary artery in Takayasu occurs in about 10%
      patients, and the coronary artery aneurysm is the least common manifestation.
      Here, we describe a case of Takayasu arteritis with abdominal aortic aneurysm
      rupture and coronary artery aneurysm. This patient also had associated systemic
      inflammatory diseases like sarcoidosis and Hashimoto's thyroiditis. 

PMID- 24908553
TI  - Synthesis of the allelochemical alliarinoside present in garlic mustard (Alliaria
      petiolata), an invasive plant species in North America.
AB  - The allelochemical alliarinoside present in garlic mustard (Alliaria petiolata),
      an invasive plant species in North America, was chemically synthesized using an
      efficient and practical synthetic strategy based on a simple reaction sequence.
      Commercially available 1,2,3,4,6-penta-O-acetyl-beta-D-glucopyranose was
      converted into prop-2-enyl 2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranoside and
      subjected to epoxidation. In a one-pot reaction, ring-opening of the epoxide
      using TMSCN under solvent free conditions followed by treatment of the formed
      trimethylsilyloxy nitrile with pyridine and phosphoryl chloride, afforded the
      acetylated beta-unsaturated nitriles (Z)-4-(2',3',4',6'-tetra-O-beta-D
      glucopyranosyloxy)but-2-enenitrile and its isomer (E)-4-(2',3',4',6'-tetra-O-beta
      D-glucopyranosyloxy)but-2-enenitrile. Deacetylation of Z- and/or E-isomers
      afforded the target molecules alliarinoside and its isomer.

PMID- 24908554
TI  - Trick elbow motions in patients with brachial plexus injuries.

PMID- 24908555
TI  - Volar carpal subluxation following lunate facet fracture.

PMID- 24908557
TI  - Cutting for a career; a discussion of the domains of surgical competence using
      expert bespoke tailoring as a metaphor for surgical practice.
AB  - Competency based surgical training uses proficiency of technical skills to
      quantify surgical competency. We believe this is an over simplification of what
      is required to be a competent surgeon. This work aims to illuminate the
      attributes of a mature, competent, thinking surgeon. A bespoke (or custom) tailor
      is highly trained craftsman who produces unique items of clothing to the
      customers' requirements. This paper uses the practice of expert bespoke tailoring
      as a metaphor for illuminating surgical training and practice. A sustained and
      evolving dialogue with a single eminent tailor identified a number of emergent
      themes. A three-year iterative process included wide reading, interviews,
      observation, discussion and reflection. These emergent themes have produced a
      provisional working framework for exploring non-technical domains of surgical
      competence. Surgical practice is a complex process, which interweaves non
      technical and technical elements in a seamless harmonious marriage of physical
      and mental processes. These processes need to be more clearly defined to allow
      the most effective training of future surgeons in the limited time now available.
      We discuss the benefits of illuminating these hidden facets of surgical practice,
      pointing out the limitations of defining competency in terms of knowledge
      acquisition and technical skills. If we are to train balanced, thinking surgeons
      for future surgical practice, and the training of future surgeons, has to be
      viewed as a complex integrated process rather than a collection of isolated
      domains. 

PMID- 24908556
TI  - Factors delaying recovery after volar plate fixation of distal radius fractures.
AB  - PURPOSE: To evaluate the factors influencing delayed functional recovery in
      patients with a distal radius fracture treated by volar plate fixation. METHODS:
      A total of 122 patients with a distal radius fracture treated by volar locking
      plate were enrolled. The wrist range of motion, grip strength, and functional
      outcome by the Michigan hand score were assessed 3, 6, and 12 months after
      surgery. The factors assessed for their influence on delayed functional recovery
      include age, sex, bone mineral density (BMD), hand dominance, the type of
      fracture, the energy of trauma, the time to surgery, and the duration of
      immobilization. A multivariate regression analysis was conducted to identify
      independent predictors of delayed functional recovery in terms of the Michigan
      hand score. RESULTS: There was a significant decrease in the wrist range of
      motion in patients with a high-energy trauma, severe type fracture, or increase
      in duration of immobilization at month 3, whereas only a severe fracture type was
      associated with a decreased range of motion after 6 and 12 months. An increase in
      age, a decrease in BMD, and high-energy trauma reduced grip strength at months 3
      and 6, whereas only an increase in age and a decrease in BMD reduced grip
      strength at month 12. According to the multivariate regression analysis, severe
      type fracture and high-energy trauma reduced functional outcomes at months 3 and
      6. Conversely, at month 12, an increase in age and a decrease in BMD reduced
      functional outcome. CONCLUSIONS: An increase in age and a decrease in BMD were
      important risk factors influencing delayed functional recovery up to 12 months
      after distal radius fracture surgery, whereas fracture severity and high-energy
      trauma were associated with decreased functional outcomes up to 6 months after
      surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 24908558
TI  - The false dichotomy of quality and quantity in the discourse around assessment in
      competency-based education.
AB  - Competency-based medical education stresses the attainment of competencies rather
      than the completion of fixed time in rotations. This sometimes leads to the
      interpretation that quantitative features of a program are of less importance,
      such as procedures practiced and weeks or months spent in clinical practice. An
      educational philosophy like "We don't require numbers of procedures completed but
      focus on competencies" suggests a dichotomy of either competency-based or time
      and procedures based education. The author argues that this dichotomy is not
      useful, and may even compromise education, as long as valid assessment of all
      relevant competencies is not possible or feasible. Requiring quantities of
      experiences of learners is not in contrast with competency-based education. 

PMID- 24908559
TI  - Structural and temperature effects on enantiomer separations of
      bicyclo[2.2.2]octane-based 3-amino-2-carboxylic acids on cinchona alkaloid-based
      zwitterionic chiral stationary phases.
AB  - Procedures for the direct high-performance liquid chromatographic enantiomer
      separation of four bicyclo[2.2.2]octane-based 3-amino-2-carboxylic acids were
      developed in polar-ionic mode on zwitterionic chiral stationary phases (CSPs)
      based on cinchonane alkaloide quinine, quinidine and chiral sulfonic acid motifs.
      The effects of the mobile phase composition including the type of acid and base
      additives, the structures of the analytes and temperature were investigated.
      Experiments were performed at constant mobile phase compositions in the
      temperature range 10-50 degrees C in order to study the effects of temperature,
      and thermodynamic parameters were calculated from plots of ln k or ln alpha vs.
      1/T. Some mechanistic aspects of the chiral recognition process are discussed
      with respect to the structures of the analytes. It was found that the
      enantiomeric separations were in most cases enthalpically driven, but
      entropically driven separation was also observed. The sequence of elution of the
      enantiomers on the pseudo-enantiomerically behaving CSPs was determined in all
      cases. 

PMID- 24908561
TI  - To sense or not to sense viral RNA--essentials of coronavirus innate immune
      evasion.
AB  - An essential function of innate immunity is to distinguish self from non-self and
      receptors have evolved to specifically recognize viral components and initiate
      the expression of antiviral proteins to restrict viral replication. Coronaviruses
      are RNA viruses that replicate in the host cytoplasm and evade innate immune
      sensing in most cell types, either passively by hiding their viral signatures and
      limiting exposure to sensors or actively, by encoding viral antagonists to
      counteract the effects of interferons. Since many cytoplasmic viruses exploit
      similar mechanisms of innate immune evasion, mechanistic insight into the direct
      interplay between viral RNA, viral RNA-processing enzymes, cellular sensors and
      antiviral proteins will be highly relevant to develop novel antiviral targets and
      to restrict important animal and human infections. 

PMID- 24908560
TI  - New delay dependent stability criteria for recurrent neural networks with
      interval time-varying delay.
AB  - This paper is concerned with the delay dependent stability criteria for a class
      of static recurrent neural networks with interval time-varying delay. By choosing
      an appropriate Lyapunov-Krasovskii functional and employing a delay partitioning
      method, the less conservative condition is obtained. Furthermore, the LMIs-based
      condition depend on the lower and upper bounds of time delay. Finally, a
      numerical example is also designated to verify the reduced conservatism of
      developed criteria. 

PMID- 24908562
TI  - Antiepileptic efficacy of lamotrigine in phenobarbital-resistant and -responsive
      epileptic rats: a pilot study.
AB  - About 25% of patients with epilepsy are refractory to treatment, so that new,
      more effective antiepileptic drugs (AEDs) are urgently needed. Animal models that
      simulate the clinical situation with individuals responding and not responding to
      treatment are important to determine mechanisms of AED resistance and develop
      novel more effective treatments. We have previously developed and characterized
      such a model in which spontaneous recurrent seizures (SRS) develop after a status
      epilepticus induced by sustained electrical stimulation of the basolateral
      amygdala. In this model, prolonged treatment of epileptic rats with phenobarbital
      (PB) results in two subgroups, PB responders and PB nonresponders. When PB
      nonresponders were treated in previous experiments with phenytoin (PHT), 83% of
      the PB-resistant rats were also resistant to PHT. In the present study we
      examined if rats with PB resistant seizures are also resistant to lamotrigine
      (LTG), using continuous EEG/video recording of spontaneous seizures over 10
      consecutive weeks. For this purpose, a new group of epileptic rats was produced
      and selected by treatment with PB into responders and nonresponders. As in
      previous studies, PB nonresponders had a significantly higher seizure frequency
      before onset of treatment. During subsequent treatment with LTG, all PB
      nonresponders and 60% of the PB responders exhibited >75% reduction of seizure
      frequency and were therefore considered as LTG responders. Plasma levels of LTG
      did not differ significantly between responders and nonresponders. The data of
      this pilot study indicate that LTG is more effective than PHT to suppress
      seizures in PB nonresponders in this model, but that not all PB responders also
      respond to LTG. Overall, our data provide further evidence that AED studies in
      post-SE TLE models are useful in determining and comparing AED efficacy and
      investigating predictors and mechanisms of pharmacoresistance.

PMID- 24908563
TI  - Seizure and radiological outcomes in children with solitary cysticercous
      granulomas with and without albendazole therapy: a retrospective case record
      analysis.
AB  - Neurocysticercosis, parasitic infestation of the central nervous system by the
      Taenia solium larvae, is a major public health problem, primarily in the
      developing countries. Seizures are the primary clinical manifestation which could
      be acute (secondary to active lesions) or remote symptomatic (due to calcified
      lesions). Cysticidal therapy is the standard of care for solitary parenchymal
      active neurocysticerci. However treatment related side effects and tendency to
      spontaneous resolution raises concern from time to time whether cysticidal
      therapy is actually required. This is a retrospective case record analysis of two
      groups of patients with solitary parenchymal neurocysticerci (group A; 171
      patients between 2000 and 2004 who did not receive cysticidal therapy, group B;
      512 patients between 2008 and 2013 who received cysticidal therapy). Group B had
      significantly more radiological resolution of lesions whereas group A reported
      significantly more seizure recurrences on antiepileptics. There was no
      significant difference in occurrence of calcification in the two groups. Overall
      patients with calcified lesions had significantly more breakthrough seizures.
      Well designed prospective studies should be planned in future to understand the
      mechanism underlying the epileptogenicity of calcified lesions and how they are
      linked to host and environment factors.

PMID- 24908564
TI  - Long-term safety and efficacy of eslicarbazepine acetate in patients with focal
      seizures: results of the 1-year ESLIBASE retrospective study.
AB  - BACKGROUND: Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED)
      licensed as adjunctive therapy in adults with partial-onset or focal seizures.
      OBJECTIVE: To evaluate in a clinical practice setting the long-term efficacy and
      safety of ESL in patients with focal seizures. METHODS: ESLIBASE was a
      retrospective study that included all patients with focal seizures who started
      ESL between January 2010 and July 2012 at 12 hospitals. ESL was prescribed
      individually according to real-life practice. Efficacy and safety were evaluated
      over 1 year. Switching from carbamazepine (CBZ) and oxcarbazepine (OXC) was
      assessed. RESULTS: Three hundred and twenty-seven patients were included; 78% of
      patients were taking >=2 other AEDs at baseline. Most (87%) began ESL because of
      poor seizure control and 13% because of adverse events (AEs) with CBZ or OXC.
      After 1 year, 237 patients (72.4%) remained on ESL. At 3, 6 and 12 months, the
      responder rate was 46.3%, 57.9%, and 52.5%, and 21.0%, 28.0%, and 25.3% of
      patients were seizure free. The responder rate significantly increased when ESL
      was combined with a non-sodium channel-targeting drug (non-SC drug) (66.7%)
      versus an SC drug (47.7%; p<0.001). At 12 months, 40.7% of patients had >=1 AE;
      AEs led to treatment discontinuation in 16.2%. Dizziness, nausea, and somnolence
      were the most common AEs. The tolerability profile improved in >50% of the
      patients who switched from CBZ or OXC to ESL because of AEs. CONCLUSIONS: ESL was
      well tolerated and effective in a real-world setting over 1 year. Side-effect
      profile improved when OXC and CBZ recipients were switched to ESL.

PMID- 24908565
TI  - [An exceptional association of tuberculosis: clavicular and metacarpal].
AB  - We report an exceptional association of metacarpal and clavicular tuberculosis in
      a two-year-old child with SAFA2 sickle cell disease. We emphasize the role of
      imaging (X-ray and CT scan) in this work. The definitive diagnosis is confirmed
      by the pathological examination of biopsy samples. This location should be known
      in endemic tuberculosis areas. 

PMID- 24908566
TI  - MiR-135a promotes renal fibrosis in diabetic nephropathy by regulating TRPC1.
AB  - AIMS/HYPOTHESIS: The contribution of aberrantly expressed microRNAs (miRNAs) to
      diabetic nephropathy in vivo is poorly understood. METHODS: Integrated
      comparative miRNA array profiling was used to examine the expression of serum
      miRNAs in patients with diabetic nephropathy. The abundance of miRNA-135a (miR
      135a) was measured by real-time quantitative PCR in the serum and kidney tissues
      of patients with diabetic nephropathy. The luciferase assay combined with
      mutation and immunoblotting was used to screen and verify the bioinformatically
      predicted miRNAs. Ca(2+) entry or intracellular Ca(2+) ([Ca(2+)]i) was performed
      by imaging Fura-2/AM-loaded cells using a fluorescence microscopy system. The
      role of miR-135a in vivo was explored with locked nucleic acid antisense
      oligonucleotides. RESULTS: MiR-135a was markedly upregulated in serum and renal
      tissue from patients with diabetic nephropathy, as well from db/db mice, and this
      was associated with the development of microalbuminuria and renal fibrosis.
      Furthermore, we identified transient receptor potential cation channel, subfamily
      C, member 1 (TRPC1) as a target of miR-135a during renal injury. We demonstrated
      that overexpression of TRPC1 was able to reverse the pathological effects of miR
      135a on promoting proliferation of mesangial cells and increasing synthesis of
      extracellular matrix proteins. Moreover, miR-135a attenuated store depletion
      induced Ca(2+) entry into cells by regulating TRPC1. Importantly, knockdown of
      miR-135a in diabetic kidneys restored levels of TRPC1 and reduced synthesis of
      fibronectin and collagen I in vivo. Suppressing TRPC1 levels to prevent Ca(2+)
      entry into cells may be a mechanism whereby miR-135a promotes renal fibrosis in
      diabetic kidney injury. CONCLUSIONS/INTERPRETATION: These findings suggest an
      important role for miR-135a in renal fibrosis and inhibition of miR-135a might be
      an effective therapy for diabetic nephropathy.

PMID- 24908568
TI  - Effect of leaf dehydration duration and dehydration degree on PSII photochemical
      activity of papaya leaves.
AB  - Although the effect of dehydration on photosynthetic apparatus has been widely
      studied, the respective effect of dehydration duration and dehydration degree was
      neglected. This study showed that, when leaves dehydrated in air, the PSII
      activities of leaves decreased with the decline of leaf relative water content
      (RWC). Unexpectedly, when leaves dehydrated to same RWC, the decreases in Fv/Fm,
      Psio and RC/CSm were lower in leaves dehydrating at 43  degrees C than those at
      25  degrees C. However, to reach the same RWC, leaves dehydrating at 43  degrees
      C experienced 1/6 of the dehydration duration for leaves dehydrating at 25 
      degrees C. To distinguish the respective effect of dehydration degree and
      dehydration duration on photosynthetic apparatus, we studied the PSII activities
      of leaves treated with different concentration of PEG solutions. Increasing
      dehydration degree aggravated the decline of Fv/Fm, Psio and RC/CSm in leaves
      with the same dehydration duration, while prolonging the dehydration duration
      also exacerbated the decline of Fv/Fm, Psio and RC/CSm in leaves with identical
      dehydration degree. With the same dehydration degree and duration, high
      temperature enhanced the decrease of Fv/Fm, Psio and RC/CSm in the leaves. When
      leaves dehydrated in air, the effect of high temperature was underestimated due
      to reduction of dehydration duration. The results demonstrated that, dehydration
      degree and duration both play important roles in damage to photosynthetic
      apparatus. We suggest that, under combined stresses, the effects of dehydration
      degree and duration on plants should be considered comprehensively, otherwise,
      partial or incorrect results may be obtained. 

PMID- 24908567
TI  - Fracture risk in diabetic elderly men: the MrOS study.
AB  - AIMS/HYPOTHESIS: Diabetes mellitus is associated with increased fracture risk in
      women but few studies are available in men. To evaluate the relationship between
      diabetes and prospective non-vertebral fractures in elderly men, we used data
      from the Osteoporotic Fractures in Men (MrOS) study. METHODS: The MrOS enrolled
      5,994 men (aged >=65 years). Diabetes (ascertained by self-report, the use of
      medication for diabetes or an elevated fasting glucose level) was reported in 881
      individuals, 80 of whom were using insulin. Hip and spine bone mineral density
      (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the
      men were followed for incident non-vertebral fractures using a triannual (3
      yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional
      hazards model was used to assess the incident risk of fractures. RESULTS: In
      models adjusted for age, race, clinic site and total hip BMD, the risk of non
      vertebral fracture was higher in men with diabetes compared with normoglycaemic
      men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46,
      95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk
      of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After
      multivariable adjustment, the risk of non-vertebral fracture remained higher only
      among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).
      CONCLUSIONS/INTERPRETATION: Men with diabetes who are using insulin have an
      increased risk of non-vertebral fracture for a given age and BMD.

PMID- 24908569
TI  - Planning target volumes determine weight loss in highly conformal radiation
      therapy in head and neck cancers--a validation study.

PMID- 24908570
TI  - Radiation-enhanced cell migration/invasion process: a review.
AB  - Radiation therapy is a keystone treatment in cancer. Photon radiation has proved
      its benefits in overall survival in many clinical studies. However, some patients
      present local recurrences or metastases when cancer cells survive to treatment.
      Metastasis is a process which includes adhesion of the cell to the extracellular
      matrix, degradation of the matrix by proteases, cell motility, intravasation in
      blood or lymphatic vessels, extravasation in distant parenchyma and development
      of cell colonies. Several studies demonstrated that ionizing radiation might
      promote migration and invasion of tumor cells by intricate implications in the
      micro-environment, cell-cell junctions, extracellular matrix junctions, proteases
      secretion, and induction of epithelial-mesenchymal transition. This review
      reports various cellular pathways involved in the photon-enhanced cell invasion
      process for which potential therapeutic target may be employed for enhancing
      antitumor effectiveness. Understanding these mechanisms could lead to therapeutic
      strategies to counter the highly invasive cell lines via specific inhibitors or
      carbon-ion therapy. 

PMID- 24908571
TI  - miR-1202 is a primate-specific and brain-enriched microRNA involved in major
      depression and antidepressant treatment.
AB  - Major depressive disorder (MDD) is a prevalent mood disorder that is associated
      with differential prefrontal brain expression patterns. Treatment of MDD includes
      a variety of biopsychosocial approaches. In medical practice, antidepressant
      drugs are the most common treatment for depressive episodes, and they are among
      the most prescribed medications in North America. Although antidepressants are
      clearly effective, particularly for moderate to severe depressive episodes, there
      is variability in how individuals respond to antidepressant treatment. Failure to
      respond has individual, economic and social consequences for patients and their
      families. Several lines of evidence demonstrate that genes are regulated through
      the activity of microRNAs (miRNAs), which act as fine-tuners and on-off switches
      of gene expression. Here we report on complementary studies using postmortem
      human brain samples, cellular assays and samples from clinical trials of patients
      with depression and show that miR-1202, a miRNA specific to primates and enriched
      in the human brain, is differentially expressed in individuals with depression.
      Additionally, miR-1202 regulates expression of the gene encoding metabotropic
      glutamate receptor-4 (GRM4) and predicts antidepressant response at baseline.
      These results suggest that miR-1202 is associated with the pathophysiology of
      depression and is a potential target for new antidepressant treatments. 

PMID- 24908572
TI  - Narrow band imaging vs. high definition colonoscopy for detection of colorectal
      adenomas in patients with positive faecal occult blood test: a randomised trial.
AB  - BACKGROUND: The impact of narrow band imaging in improving the adenoma detection
      rate in a screening scenario is still unclear. AIM: To evaluate whether narrow
      band imaging compared with high definition white light colonoscopy can enhance
      the adenoma detection rate during screening colonoscopy. METHODS: Consecutive
      patients presenting for screening colonoscopy were included into this study and
      were randomly assigned to the narrow band imaging group (Group 1) or standard
      colonoscopy group (Group 2). Primary end point was the adenoma detection rate and
      secondary aim was the detection rate of advanced adenomas. RESULTS: Overall, 117
      patients were allocated to Group 1 and 120 to Group 2. Both the adenoma detection
      rate and the detection rate of advanced adenomas were not significantly different
      between the two groups (respectively, 52.1% vs. 55%, RR=0.95, 95% CI 0.75-1.20;
      32.5% vs. 44.2%, RR=0.74, 95% CI 0.53-1.02). No significant difference between
      the proportions of polypoid and flat adenomas was found. Male gender, no prior
      history of screening, and endoscopist's adenoma detection rate were independent
      predictive factors of higher advanced adenoma detection rate. CONCLUSIONS: In a
      screening scenario, narrow band imaging did not improve the adenoma nor advanced
      adenoma detection rates compared to high definition white light colonoscopy.

PMID- 24908573
TI  - Management of patients over 80 years of age treated with resection for localised
      colon cancer: results from a French referral centre.
AB  - BACKGROUND: Few data are available on management of very elderly colon cancer
      patients, especially concerning the parameters of therapeutic decisions and the
      role of geriatricians. METHODS: We retrospectively reviewed the charts of
      patients over 80 years of age who underwent surgery for a localised colon cancer
      in a French academic hospital. RESULTS: A total of 176 patients underwent surgery
      (postoperative morbidity and mortality rates: 25% and 6.7%). Adjuvant
      chemotherapy was discussed at a multidisciplinary team meeting for 91% of stage
      III patients, but only 13.5% of them were treated. Twenty-five patients relapsed:
      19 were discussed at the multidisciplinary meeting and 16 were treated (5 had a
      metastasectomy). Despite their increase with time, geriatric assessments were
      infrequent, 17% (33% after 2006), and had no impact on postoperative morbi
      mortality. Median overall survival and recurrence-free survival were 65.3 months
      and 65.1 months, respectively. Age, emergency surgery, and Charlson comorbidity
      index were independent prognostic factors. CONCLUSION: Selected elderly colon
      cancer patients have significant access to surgery. However, postoperative morbi
      mortality rates remain high and adjuvant chemotherapy rarely prescribed.
      Perioperative geriatric assessment, especially before surgery, should be
      routinely proposed to these patients to evaluate its impact on postoperative
      morbi-mortality and prescription of adjuvant treatment.

PMID- 24908574
TI  - Fibrolamellar carcinoma in a 62 year-old patient with human immunodeficiency
      virus infection.

PMID- 24908575
TI  - Epidemiology and prognosis of synchronous and metachronous colon cancer
      metastases: a French population-based study.
AB  - BACKGROUND: Epidemiological data on synchronous and metachronous metastatic colon
      cancer are scarce. We assessed epidemiological characteristics and survival in
      synchronous and metachronous metastatic colon cancer in a French population.
      METHODS: Our study included 932 cases of metastatic colon cancer diagnosed in
      1999-2010 and registered in a population-based cancer registry; 758 were
      synchronous colon metastases and 174 metachronous metastases from resected
      primary colon cancers diagnosed in 1999-2005. Univariate relative survival was
      calculated and a multivariate model with proportional hazard applied to net
      survival by interval was used. RESULTS: Mean age at diagnosis was 71.1 years for
      patients with metachronous metastasis and 71.4 years for those with synchronous
      metastasis (p=0.818). Patients with metachronous metastasis were more likely to
      have R0 resection (Odds Ratio: 3.05 [1.96-4.76], p<0.001) than patients with
      synchronous metastasis. Five-year relative survival was 7.2% for synchronous
      metastasis and 17.6% for metachronous metastasis (p<0.001), but did not differ
      significantly for patients with R0 resection (47.3% and 61.5% respectively,
      p=0.120). For patients not receiving chemotherapy risk of death was significantly
      lower in the metachronous metastasis group (Hazard Ratio=0.44 [0.32-0.60],
      p<0.001). CONCLUSIONS: On a population basis, synchronous metastasis is an
      independent poor prognostic factor in colon cancer. Chemotherapy and resection of
      all metastatic sites significantly improved the outcome in patients with
      synchronous metastasis.

PMID- 24908576
TI  - Short tandem repeat typing on the 454 platform: strategies and considerations for
      targeted sequencing of common forensic markers.
AB  - To investigate the feasibility of next generation sequencing technology (NGS) for
      the multiplex detection and sequence production of short tandem repeats (STRs)
      from degraded and low DNA quantity samples, standard polymerase chain reaction
      amplification methods were used to enrich for commonly employed STR markers.
      Samples were amplified with two multiplexing strategies: a multiplex containing
      thirteen miniSTR markers and a series of multiplexes containing four miniSTR
      markers each. Each sample multiplex was barcoded with a sample-specific multiplex
      identifier for subsequent parallel tagged sequencing on the GS Junior System (454
      Life Sciences, a Roche company, Branford, CT). Sequencing results from over fifty
      DNA extracts representing both pristine samples and low-quality evidentiary
      specimens reflected known genotypes and were consistent across multiple extracts
      and/or amplifications of the same sample. Furthermore, the NGS data revealed
      sequence information not available with standard capillary electrophoresis-based
      detection alone. For the population samples tested, a total of 152 single
      nucleotide polymorphisms or insertions/deletions were identified in over 935
      recovered alleles, averaging one polymorphism for every six recovered alleles.
      For three of the loci, the sequence information doubled the number of alleles
      detected via traditional STR typing by fragment analysis. In addition, twenty
      eight of these variants were only seen once within our dataset, highlighting the
      potential for discrimination among individuals. These additional data are likely
      to be particularly valuable in missing persons and disaster victim identification
      cases for which only partial profiles may be recovered and/or only distant kin
      are available as references. And, considering the opportunity to target only
      small amplicons with NGS, this type of STR typing will allow for greater
      information recovery from challenging casework samples. While our results
      highlight the potential of new technologies for recovering discriminatory genetic
      information from evidentiary specimens, our data also reveal the complexities of
      NGS-based STR typing, both in terms of the laboratory assays themselves as well
      as the downstream data processing and analysis. 

PMID- 24908577
TI  - Replicating the microbial community and water quality performance of full-scale
      slow sand filters in laboratory-scale filters.
AB  - Previous laboratory-scale studies to characterise the functional microbial
      ecology of slow sand filters have suffered from methodological limitations that
      could compromise their relevance to full-scale systems. Therefore, to ascertain
      if laboratory-scale slow sand filters (L-SSFs) can replicate the microbial
      community and water quality production of industrially operated full-scale slow
      sand filters (I-SSFs), eight cylindrical L-SSFs were constructed and were used to
      treat water from the same source as the I-SSFs. Half of the L-SSFs sand beds were
      composed of sterilized sand (sterile) from the industrial filters and the other
      half with sand taken directly from the same industrial filter (non-sterile). All
      filters were operated for 10 weeks, with the microbial community and water
      quality parameters sampled and analysed weekly. To characterize the microbial
      community phyla-specific qPCR assays and 454 pyrosequencing of the 16S rRNA gene
      were used in conjunction with an array of statistical techniques. The results
      demonstrate that it is possible to mimic both the water quality production and
      the structure of the microbial community of full-scale filters in the laboratory 
      at all levels of taxonomic classification except OTU - thus allowing comparison
      of LSSF experiments with full-scale units. Further, it was found that the sand
      type composing the filter bed (non-sterile or sterile), the water quality
      produced, the age of the filters and the depth of sand samples were all
      significant factors in explaining observed differences in the structure of the
      microbial consortia. This study is the first to the authors' knowledge that
      demonstrates that scaled-down slow sand filters can accurately reproduce the
      water quality and microbial consortia of full-scale slow sand filters. 

PMID- 24908578
TI  - Characterisation of dissolved organic matter fluorescence properties by PARAFAC
      analysis and thermal quenching.
AB  - The fluorescence intensity of dissolved organic matter (DOM) in aqueous samples
      is known to be highly influenced by temperature. Although several studies have
      demonstrated the effect of thermal quenching on the fluorescence of DOM, no
      research has been undertaken to assess the effects of temperature by combining
      fluorescence excitation - emission matrices (EEM) and parallel factor analysis
      (PARAFAC) modelling. This study further extends previous research on thermal
      quenching by evaluating the impact of temperature on the fluorescence of DOM from
      a wide range of environmental samples, in the range 20  degrees C - 0  degrees C.
      Fluorescence intensity increased linearly with respect to temperature decrease at
      all temperatures down to 0  degrees C. Results showed that temperature affected
      the PARAFAC components associated with humic-like and tryptophan-like components
      of DOM differently, depending on the water type. The terrestrial humic-like
      components, C1 and C2 presented the highest thermal quenching in rural water
      samples and the lowest in urban water samples, while C3, the tryptophan-like
      component, and C4, a reprocessed humic-like component, showed opposite results.
      These results were attributed to the availability and abundance of the components
      or to the degree of exposure to the heat source. The variable thermal quenching
      of the humic-like components also indicated that although the PARAFAC model
      generated the same components across sites, the DOM composition of each component
      differed between them. This study has shown that thermal quenching can provide
      additional information on the characteristics and composition of DOM and
      highlighted the importance of correcting fluorescence data collected in situ.

PMID- 24908579
TI  - Influence of duration and dose of metformin on cobalamin deficiency in type 2
      diabetes patients using metformin.
AB  - Metformin use is associated with cobalamin (vitamin B12) deficiency. However, the
      influence of both duration and dose of metformin is unclear. Studies using
      holotranscobalamin, a marker for cellular cobalamin deficiency, are scarce. We
      therefore investigated the prevalence of cobalamin deficiency in type 2 diabetes
      patients using both markers, and its relation with duration and dose of metformin
      use. This cross-sectional study among 550 type 2 diabetes patients using
      metformin (mean daily dose 1,306 mg; mean duration 64 months) was conducted in
      four primary care centers in Utrecht, the Netherlands. Cobalamin and
      holotranscobalamin concentrations were measured at the annual diabetes check.
      Detailed information on metformin use and confounding variables was collected
      from medical records. The prevalence of a cobalamin deficiency was 28.1 %, while
      a holotranscobalamin deficiency occurred in 3.9 % of the patients. Adjusting for
      multiple confounders, a 1 mg/day increase in daily metformin dose was associated
      (p < 0.001) with 0.042 (95 % CI -0.060, -0.023) decrease in cobalamin
      concentrations. Similarly, a 10 g increase of cumulative metformin dose was
      associated (p = 0.006) with -0.070 (-0.12, -0.021) lower cobalamin concentrations
      after adjustment for confounders. Duration of metformin use was not associated
      with cobalamin concentrations after multivariable adjustment. Similar results
      were observed for holotranscobalamin. Cobalamin deficiency occurs frequently
      among diabetes patients using metformin. A higher daily and cumulative doses of
      metformin were strongly associated with lower cobalamin and holotranscobalamin
      concentrations, while duration was not. It is thus important to account for
      metformin dose in recommendations for screening for cobalamin deficiency.

PMID- 24908580
TI  - [The 2013 Sixto Obrador Award. A triple-axis topographical model for surgical
      planning of craniopharyngiomas. Part I: historical review of the topographical
      diagnosis and classification schemes of craniopharyngiomas].
AB  - INTRODUCTION AND OBJECTIVES: This study reviews the historical evolution of
      pathological, neuroradiological and surgical evidence that influenced the
      topographical concepts and classification schemes of craniopharyngiomas. MATERIAL
      AND METHODS: An extensive, systematic analysis of the surgical series of
      craniopharyngiomas reported in the literature was performed (n=145 series, 4,588
      tumours) to describe the fundamental anatomical findings guiding the
      topographical classification schemes used for this tumour throughout history.
      These findings were compared with topographical relationships reported for well
      described operated craniopharyngiomas (n=224 cases) as well as for non-operated
      cases studied in autopsies (n=201 cases). RESULTS: Two major variables define the
      topography of a craniopharyngioma: its position relative to the sellar diaphragm
      and its degree of invasion of the third ventricle floor. Suprasellar lesions
      displacing the third ventricle floor upwards (pseudointraventricular
      craniopharyngiomas) are amenable to safe, radical resection and must be
      differentiated from lesions developing primarily within the third ventricle floor
      (infundibulo-tuberal or not strictly intraventricular craniopharyngiomas). The
      latter group typically shows tight, circumferential adhesion to the third
      ventricle floor and represents approximately 40% of all cases. CONCLUSIONS: A
      triple-axis topographical model for craniopharyngiomas that includes the degree
      of hypothalamus invasion is useful in planning surgical approach and degree of
      resection. The group of infundibulo-tuberal craniopharyngiomas associates the
      highest risk of hypothalamic injury (50%). The endoscopically-assisted extended
      transsphenoidal approach provides a proper view to assess the topography of the
      craniopharyngioma and its degree of adherence to the hypothalamus.

PMID- 24908581
TI  - Development of a Short-Form of the RCOPE for Use with Bereaved College Students.
AB  - Bereavement is being increasingly recognized as a key issue in college
      populations (Balk in Mortality 2:207-220, 1997; Balk et al. in Death Stud 34:459
      468, 2010). However, there is currently a dearth of research on the impact that
      the loss of a loved one has on college students and the ways that college
      students cope during the grieving process. This lack of research, particularly
      among younger groups, is problematic as researchers have shown that emerging
      adults experience a surprisingly high number of losses and are an at-risk group
      for poor post-loss outcomes (Servaty-Seib and Taub 2010; Servaty-Seib and
      Hamilton 2006; Arnett in Am Psychol 55(5):469, 2000). Religion is a common way
      that individuals cope with bereavement (Frantz et al. in Pastor Psychol 44(3):151
      163, 1996) and may also be commonly used by college students to manage everyday
      stress (Merrill et al. 2009). The RCOPE (Pargament et al. in J Clin Psychol
      56(4):519-543, 2000; J Health Psychol 9:713-730, 2004) is a frequently used
      measure of religious coping that has recently been evaluated for use with a
      bereaved undergraduate population. Lord and Gramling (2014) examined the factor
      structure of the RCOPE and concluded that overlap between the positive and
      negative religious coping subscales when used with a bereaved undergraduate
      sample detracted from the predictive utility of the instrument. The researchers
      provided evidence for the use of a new 2-factor, 39-item version of the RCOPE
      with the bereaved college student population. The current study replicated Lord
      and Gramling (2014) with a large follow-up sample of bereaved undergraduates.
      Participants (N = 677) consisted of individuals who had lost a loved one within
      the past 2 years, had a mean age of 19.1, and were predominantly female (62%)
      underclassmen (84% freshman or sophomore status). A majority of participants
      (68%) were identified as Christian. Exploratory factor analyses closely mimicked
      the results of the previous study, and the number of items was further reduced in
      order to provide a briefer version of the scale for use in future research.
      Hierarchical regression models demonstrated discriminate, convergent, and
      predictive validity of the instrument.

PMID- 24908582
TI  - Religiosity and religious coping in patients with cardiovascular disease: change
      over time and associations with illness adjustment.
AB  - Little is known about the longitudinal relationship between
      religiosity/spirituality (R/S) and patient physical and mental health in patients
      with cardiovascular disease. Forty-three patients with a first-time myocardial
      infarction or coronary artery revascularization bypass surgery completed measures
      of religiosity, religious coping, quality of life (QOL), and weight prior to a
      cardiac rehabilitation program and 1 and 2 years later. R/S changed over time;
      the direction of the change varied by type of R/S. Increases in religiosity were
      associated with increases in weight and QOL; increases in religious coping were
      associated with decreases in weight and increases in QOL.

PMID- 24908583
TI  - Evil, Child Abuse and the Caring Professions.
AB  - The aim of this paper is to explore the ways in which the concept of evil has
      been invoked in relation to child abuse. First, the scene is set by juxtaposing
      professional discourses which have eschewed the concept of evil and public
      opinion which is affronted by the evil of child abuse. Second, I will discuss the
      work of some therapists in the USA whose work with perpetrators and survivors has
      led them to frame the causes and consequences of child abuse in terms of moral
      evil. Third, I will draw upon case studies of Satanic abuse and spirit possession
      in the UK to illustrate that some social workers and religious communities have
      interpreted child abuse as an outcome of or as an antidote to metaphysical evil.
      Finally, there is a critical appraisal of the merits of referencing moral and
      metaphysical evil in the discourses of caring professionals, with a suggestion
      that a mythical-metaphorical conception of evil could be a more flexible and
      fruitful resource for therapeutic work. 

PMID- 24908584
TI  - Comparative responses to metal oxide nanoparticles in marine phytoplankton.
AB  - A series of experiments was undertaken on three different marine microalgae to
      compare the effect of two metal oxide nanoparticles (NPs) on different
      physiological responses to stress: zinc oxide (ZnO), a known toxic compound for
      microalgae, and the never before tested yttrium oxide (Y2O3). The effect of these
      potential pollutants was estimated for different physiological variables and
      temporal scales: Growth, carbon content, carbon-to-nitrogen (C:N) ratio, and
      chlorophyll fluorescence were evaluated in long-term assays, and reactive oxygen
      species (ROS) production was evaluated in a short-term assay. Population growth
      was the most susceptible variable to the acute toxic effects of both NPs as
      measured in terms of number of cells and of biomass. Although Phaeodactylum
      tricornutum and Alexandrium minutum were negatively affected by ZnO NPs, this
      effect was not detected in Tetraselmis suecica, in which cell growth was
      significantly decreased by Y2O3 NPs. Biomass per cell was negatively affected in
      the most toxic treatments in T. suecica but was positively affected in A.
      minutum. ZnO treatments induced a sharper decrease in chlorophyll fluorescence
      and higher ROS than did Y2O3 treatments. The pronounced differences observed in
      the responses between the species and the physiological variables tested
      highlight the importance of analyzing diverse groups of microalgae and various
      physiological levels to determine the potential effects of environmental
      pollutants.

PMID- 24908585
TI  - Oxidative stress and genotoxicity of the ionic liquid 1-octyl-3-methylimidazolium
      bromide in zebrafish (Danio rerio).
AB  - Ionic liquids (ILs) have a great reputation due to their negligible volatility,
      designability, good stability, and ability to be recycled. They are considered to
      be "green" solvents and have great promise in many fields. In recent years, the
      toxicities of ILs have garnered increasing attention as reported by a number of
      studies. However, previous studies have primarily focused on their lethal
      toxicities, and data were limited on their toxic effects at nonlethal doses. We
      performed a study on the toxic effects of 1-octyl-3-methylimidazolium bromide
      ([Omim]Br) on zebrafish. During a 28-day period, male and female zebrafish were
      separately exposed to sequential concentrations (0, 5, 10, 20, and 40 mg/L) of
      [Omim]Br. Fishes were sampled after 7, 14, 21, and 28 days of exposure, and
      reactive oxygen species (ROS) levels, activities of antioxidant enzymes
      (superoxide dismutase and catalase), lipid peroxidation (LPO), and DNA damage in
      fish livers were measured. ROS, LPO, and DNA damage were all induced by the ionic
      liquid, and antioxidant enzyme activities increased at the beginning and then
      decreased. These phenomena demonstrate that [Omim]Br can induce oxidative stress
      and DNA damage in zebrafish.

PMID- 24908586
TI  - A mass balance approach to investigating geochemical controls on secondary water
      quality impacts at a crude oil spill site near Bemidji, MN.
AB  - Secondary water quality impacts can result from a broad range of coupled
      reactions triggered by primary groundwater contaminants. Data from a crude-oil
      spill research site near Bemidji, MN provide an ideal test case for investigating
      the complex interactions controlling secondary impacts, including depleted
      dissolved oxygen and elevated organic carbon, inorganic carbon, CH4, Mn, Fe, and
      other dissolved ions. To better understand these secondary impacts, this study
      began with an extensive data compilation of various data types, comprising
      aqueous, sediment, gas, and oil phases, covering a 260m cross-sectional domain
      over 30years. Mass balance calculations are used to quantify pathways that
      control secondary components, by using the data to constrain the sources and
      sinks for the important redox processes. The results show that oil constituents
      other than BTEX (benzene, toluene, ethylbenzene, o-, m- and p-xylenes), including
      n-alkanes and other aromatic compounds, play significant roles in plume evolution
      and secondary water quality impacts. The analysis underscores previous results on
      the importance of non-aqueous phases. Over 99.9% of the Fe(2+) plume is
      attenuated by immobilization on sediments as Fe(II) and 85-95% of the carbon
      biodegradation products are outgassed. Gaps identified in carbon and Fe mass
      balances and in pH buffering mechanisms are used to formulate a new conceptual
      model. This new model includes direct out-gassing of CH4 and CO2 from organic
      carbon biodegradation, dissolution of directly produced CO2, and sorption with
      H(+) exchange to improve pH buffering. The identification of these mechanisms
      extends understanding of natural attenuation of potential secondary impacts at
      enhanced reductive dechlorination sites, particularly for reduced Fe plumes,
      produced CH4, and pH perturbations. 

PMID- 24908587
TI  - Effects of a 6-month Tai Chi Qigong program on arterial hemodynamics and
      functional aerobic capacity in survivors of nasopharyngeal cancer.
AB  - PURPOSE: Survivors of nasopharyngeal cancer (NPC) often sustain cardiovascular
      complications after conventional cancer treatments. Tai Chi (TC) Qigong training
      may be a viable way to improve peripheral circulatory status and aerobic capacity
      in this population. The objective of this study was to evaluate the effects of a
      6-month TC Qigong training program on blood flow velocities and resistance,
      palmar skin temperature, and functional aerobic capacity in survivors of NPC.
      METHODS: Twenty-five and 27 survivors of NPC volunteered to join the intervention
      group (mean age, 55.4 +/- 7.5 years) and control group (mean age, 58.7 +/- 9.5
      years), respectively. The intervention group underwent a TC Qigong training
      program-the modified 18 Forms TC Internal Qigong-for 6 months, while the control
      group received no training. Peripheral arterial blood flow velocities and
      resistance, palmar skin temperature, and functional aerobic capacity were
      measured by a Doppler ultrasound machine, an infrared thermometer, and six-minute
      walk test, respectively. All outcomes were assessed at baseline, mid-intervention
      (3-month), post-intervention (6-month), and follow-up (12-month) periods.
      RESULTS: The TC Qigong group had higher diastolic blood flow velocity (p =
      0.010), lower arterial blood flow resistance (p = 0.009), and higher palmar skin
      temperature (p = 0.004) than the control group after TC Qigong training. However,
      only the diastolic blood flow velocity was higher in the TC Qigong group than in
      the control group during the no-training follow-up period (p = 0.032).
      Additionally, an improvement in functional aerobic capacity was found in the
      intervention group after TC Qigong training (p < 0.008) but not in the control
      group over time (p > 0.008). CONCLUSIONS: TC Qigong training may improve
      peripheral circulatory status and functional aerobic capacity among people
      treated for NPC. However, this is only a pilot study and future definitive trials
      are needed to confirm the results. IMPLICATIONS FOR CANCER SURVIVORS: TC Qigong
      may have enormous potential as a rehabilitation intervention for survivors of NPC
      to improve arterial hemodynamics and functional aerobic capacity.

PMID- 24908588
TI  - Glaucoma severity affects diffusion tensor imaging (DTI) parameters of the optic
      nerve and optic radiation.
AB  - OBJECTIVES: To evaluate whether MR diffusion tensor imaging (DTI) of the optic
      nerve and optic radiation in glaucoma patients provides parameters to
      discriminate between mild and severe glaucoma and to determine whether DTI
      derived indices correlate with retinal nerve fibre layer (RNFL) thickness.
      METHODS: 3-Tesla DTI was performed on 90 subjects (30 normal, 30 mild glaucoma
      and 30 severe glaucoma subjects) and the FA and MD of the optic nerve and optic
      radiation were measured. The categorisation into mild and severe glaucoma was
      done using the Hodapp-Parrish-Anderson (HPA) classification. RNFL thickness was
      also assessed on all subjects using OCT. Receiver operating characteristic (ROC)
      analysis and Spearman's correlation coefficient was carried out. RESULTS: FA and
      MD values in the optic nerve and optic radiation decreased and increased
      respectively as the disease progressed. FA at the optic nerve had the highest
      sensitivity (87%) and specificity (80%). FA values displayed the strongest
      correlation with RNFL thickness in the optic nerve (r=0.684, p <= 0.001) while MD
      at the optic radiation showed the weakest correlation with RNFL thickness (r=
      0.360, p <= 0.001). CONCLUSIONS: The high sensitivity and specificity of DTI
      derived FA values in the optic nerve and the strong correlation between DTI-FA
      and RNFL thickness suggest that these parameters could serve as indicators of
      disease severity.

PMID- 24908589
TI  - Quantitative analysis of contrast-enhanced ultrasonography of the bowel wall can
      predict disease activity in inflammatory bowel disease.
AB  - PURPOSE: To evaluate the accuracy of quantitative analysis of bowel wall
      enhancement in inflammatory bowel disease (IBD) with contrast enhanced ultrasound
      (CEUS) by comparing the results with vascular density in a biopsy sample from the
      same area of the intestinal tract, and to determine the usefulness of this
      analysis for the prediction of disease activity. MATERIALS AND METHODS: This
      prospective study was approved by our institute's ethics committee and all
      patients gave written informed consent. We enrolled 33 consecutive adult patients
      undergoing colonoscopy and biopsy for IBD. All patients underwent CEUS and the
      results were quantitatively analyzed. Vessel count per high-power field on biopsy
      specimens was compared with colonoscopy, baseline ultrasonography, and CEUS
      findings, and with analysis of peak intensity, time to peak, regional blood
      volume, mean transit time, and regional blood flow. Results in patients with high
      and low vascular density were compared using Fisher's test, t-test, Pearson's
      correlation test, and receiver operating characteristic curve (ROC) analysis.
      Cutoff values were determined using ROC analysis, and sensitivity and specificity
      were calculated. RESULTS: High vascular density (>265 vessels per field) on
      histological examination was significantly correlated with active disease on
      colonoscopy, baseline ultrasonography, and CEUS (p<.0001). Quantitative analysis
      showed a higher enhancement peak, a shorter time to peak enhancement, a higher
      regional blood flow and regional blood volume in patients with high vascular
      density than in those with low vascular density. Cutoff values to distinguish
      between active and inactive disease were identified for peak enhancement
      (>40.5%), and regional blood flow (>54.8 ml/min). CONCLUSION: Quantitative
      analysis of CEUS data correlates with disease activity as determined by vascular
      density. Quantitative parameters of CEUS can be used to predict active disease
      with high sensitivity and specificity.

PMID- 24908591
TI  - Lost in translation?: Comparing three Scandinavian translations of the Beliefs
      about Medicines Questionnaire.
AB  - OBJECTIVE: The "Beliefs about Medicines Questionnaire" (BMQ) assess balance of
      necessity and concern of medicines. The BMQ has been translated from English to
      many languages. However, the original meaning of statements, such as "My medicine
      is a mystery to me", may be lost in translation. The aim of this study is to
      compare three Scandinavian translations of the BMQ. (1) How reliable are the
      translations? (2) Are they still valid after translation? METHODS: Translated
      Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three
      native Scandinavian researchers. Linguistic differences and ambiguities in the 5
      point Likert scale and the BMQ statements were compared. RESULTS: In the
      Scandinavian translations, the Likert scale expanded beyond the original version
      at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements,
      discrepancies ranged from smaller inaccuracies toward completely different
      meaning. Some dissimilarities reflect different cultural beliefs about medicines.
      CONCLUSION: When translating questionnaires, bilingual researchers should
      scrutinize translations across similar languages to address content validity
      across different countries and languages. PRACTICE IMPLICATIONS: Our findings are
      of relevance to other BMQ translations in non-English countries, as direct
      comparisons between different translations might not be reliable or valid.

PMID- 24908590
TI  - Geriatric-specific triage criteria are more sensitive than standard adult
      criteria in identifying need for trauma center care in injured older adults.
AB  - STUDY OBJECTIVE: We evaluate the sensitivity of Ohio's 2009 emergency medical
      services (EMS) geriatric trauma triage criteria compared with the previous adult
      triage criteria in identifying need for trauma center care among older adults.
      METHODS: We studied a retrospective cohort of injured patients aged 16 years or
      older in the 2006 to 2011 Ohio Trauma Registry. Patients aged 70 years or older
      were considered geriatric. We identified whether each patient met the geriatric
      and the adult triage criteria. The outcome measure was need for trauma center
      care, defined by surrogate markers: Injury Severity Score greater than 15,
      operating room in fewer than 48 hours, any ICU stay, and inhospital mortality. We
      calculated sensitivity and specificity of both triage criteria for both age
      groups. RESULTS: We included 101,577 patients; 33,379 (33%) were geriatric.
      Overall, 57% of patients met adult criteria and 68% met geriatric criteria. Using
      Injury Severity Score, for older adults geriatric criteria were more sensitive
      for need for trauma center care (93%; 95% confidence interval [CI] 92% to 93%)
      than adult criteria (61%; 95% CI 60% to 62%). Geriatric criteria decreased
      specificity in older adults from 61% (95% CI 61% to 62%) to 49% (95% CI 48% to
      49%). Geriatric criteria in older adults (93% sensitivity, 49% specificity)
      performed similarly to the adult criteria in younger adults (sensitivity 87% and
      specificity 44%). Similar patterns were observed for other outcomes. CONCLUSION:
      Standard adult EMS triage guidelines provide poor sensitivity in older adults.
      Ohio's geriatric trauma triage guidelines significantly improve sensitivity in
      identifying Injury Severity Score and other surrogate markers of the need for
      trauma center care, with modest decreases in specificity for older adults.

PMID- 24908592
TI  - The efficacy of ultrasonography for the detection of renal stone.
AB  - OBJECTIVE: To assess the efficacy of ultrasonography (US) for detecting renal
      stone using noncontrast enhanced computed tomography (NCCT) as a standard
      reference. METHODS: We performed a retrospective study of 428 patients who
      underwent NCCT and US imaging on the same day from January 2009 to September
      2011. The sensitivity of US to detect each individual stone and at least 1 stone
      per kidney was evaluated. The detection rates according to the location and stone
      size were also examined. We compared the sizes of stones determined in the
      longest axis of NCCT and US, and performed group classification based on size to
      examine whether stone sizes measured by NCCT and US were similar. RESULTS: Of 856
      kidneys, NCCT detected 474 stones in 361 kidneys, whereas US detected 332 stones
      of 474 stones detected by NCCT, yielding a sensitivity of 70.0% and a specificity
      of 94.4%. Similarly, US alone detected at least 1 stone in 285 kidneys, yielding
      a sensitivity of 78.9% and a specificity of 83.7%. Expectedly, the detection rate
      for the left upper calyx was lower than that for other sites (P = .002), and the
      detection rate increased with stone size. Furthermore, stone sizes obtained by US
      were positively correlated with those obtained by CT, and stone size measurement
      by NCCT and US was concordant in 240 of 332 cases (72%). Importantly, stone size
      was only a factor that affected renal stone diagnosis using US. CONCLUSION: US is
      an effective imaging modality for detecting renal stones.

PMID- 24908593
TI  - Anesthetic management and outcomes for patients with pulmonary hypertension and
      intracardiac shunts and Eisenmenger syndrome: a review of institutional
      experience.
AB  - STUDY OBJECTIVE: To propose a set of recommendations for the perioperative
      management of patients with Eisenmenger syndrome and similar physiology, based on
      20 years of experience at a single institution. DESIGN: Retrospective study of
      institutional outcomes of Eisenmenger syndrome patients and patients with
      balanced or fixed right-to-left intracardiac shunts with pulmonary hypertension
      undergoing noncardiac surgery. SETTING: Single center, university-affiliated
      hospital. MEASUREMENTS: Measurements included data from patients with Eisenmenger
      syndrome or similar physiology, shunt direction, right ventricular systolic
      pressure, congestive heart failure classification, noncardiac surgery, type of
      anesthesia, echocardiographic and catheterization data, mortality within 30 days
      of surgery, choice of monitoring, and vasopressor use. MAIN RESULTS: 33 patients
      with Eisenmenger syndrome or similar physiology undergoing 53 general, regional
      and/or monitored anesthetic procedures were identified. Significant systemic
      arterial hypotension occurred in 14 individuals (26%) and oxygen desaturation in
      9 (17%) patients. Administration of an intravenous (IV) vasopressor agent during
      induction significantly decreased the incidence of hypotension. The type of IV
      induction agent did not influence hemodynamic alterations, though patients who
      received propofol experienced a trend towards increased hypotension (83% of pts)
      when a vasopressor was not used. Inhalational induction, regardless of
      vasopressor use, was more likely to result in hypotension (60% of pts). The 30
      day mortality was 3.8% (two pts). Both patients had minor elective procedures
      with monitored anesthesia care (MAC). CONCLUSIONS: Hypotension is more common in
      patients with Eisenmenger syndrome and similar physiology when a vasopressor is
      not used during the peri-induction period, regardless of induction agent.
      Etomidate tended to have better hemodynamic stability than other induction
      agents. The use of a vasopressor is recommended. We present general
      recommendations for anesthesiologists and strongly recommend use of a vasopressor
      before or during induction to reduce hypotension along with complete avoidance of
      inhalational induction. Further, MAC anesthesia has been associated with
      perioperative and 30-day mortality.

PMID- 24908594
TI  - Evidence base, epidemiology, correlations, and cause and effect: dental caries
      and head and neck cancer.

PMID- 24908595
TI  - Takayasu's arteritis--report of a case with masquerading jaw pain.
AB  - Takayasu's arteritis (TA) often referred to as pulseless disease, is a chronic
      inflammatory disorder affecting the aorta and its main branches. While the first
      reported case was documented in Japan in 1908, it does occur worldwide, but is
      more prevalent in young oriental females from China and Southeast Asia. The main
      complications of the disease are due to occlusion of major branches of the aorta.
      During the initial stages, one of the presenting symptoms may be jaw pain. This
      may prove to be a diagnostic challenge for the dentist, since many diseases cause
      orofacial pain and the diagnosis must be established before final treatment. A
      literature review of TA is presented along with clinical presentation and
      treatment modalities. A case report is also presented. 

PMID- 24908596
TI  - Evaluation of different treatment methods against denture stomatitis: a
      randomized clinical study.
AB  - OBJECTIVE: The aim of this clinical study was to determine the efficacy of
      Uncaria tomentosa (cat's claw) against denture stomatitis (DS). STUDY DESIGN:
      Fifty patients with DS were randomly assigned into 3 groups to receive 2%
      miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately,
      after 1 week of treatment, and 1 week after treatment. The clinical effectiveness
      of each treatment was measured using Newton's criteria. Mycologic samples from
      palatal mucosa and prosthesis were obtained to determinate colony forming units
      per milliliter (CFU/mL) and fungal identification at each evaluation period.
      RESULTS: Candida species were identified with HiCrome Candida and API 20C AUX
      biochemical test. DS severity decreased in all groups (P < .05). A significant
      reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups
      and remained after 14 days (P > .05). C albicans was the most prevalent
      microorganism before treatment, followed by C tropicalis, C glabrata, and C
      krusei, regardless of the group and time evaluated. U tomentosa gel had the same
      effect as 2% miconazole gel. CONCLUSIONS: U tomentosa gel is an effective topical
      adjuvant treatment for denture stomatitis.

PMID- 24908597
TI  - Content, quality, and readability of website information on dental care for
      patients with cancer.
AB  - OBJECTIVE: This study assessed content, quality, and readability of patient
      directed Internet materials about dental care support and oral
      toxicities/complications of cancer therapy. STUDY DESIGN: A total of 32 websites
      meeting inclusion criteria from a Google search using terms "cancer>dental>care"
      were categorized for parameters of content, benchmarks for website quality as
      defined by JAMA (Journal of the American Medical Association), display of the
      Health on the Net (HON) seal, and Flesch Reading Ease Score (FRES). RESULTS:
      Treatment modalities included radiation therapy, chemotherapy, stem cell
      transplant, and surgery. Dental care was discussed before, during, or after
      cancer treatment, or a combination of those. The most common oral
      toxicities/complications discussed were xerostomia, rampant caries, and
      mucositis. Only 1 site met all 4 JAMA benchmarks; 2 displayed the HON seal; only
      9% were written at the 9th-grade FRES reading level; and none were written at the
      6th- to 7th-grade level. CONCLUSIONS: Websites addressing dental care for
      patients with cancer are broad in content yet are limited in quality and are
      written at difficult reading levels.

PMID- 24908598
TI  - In vitro evaluation of the enzymatic activity profile of non-albicans Candida
      species isolated from patients with oral candidiasis with or without diabetes.
AB  - OBJECTIVE: To evaluate the expression of phospholipase (PL) and secreted aspartyl
      proteinase (SAP) by Candida glabrata and C tropicalis obtained from the denture
      biofilms of healthy participants (16 isolates), patients with oral candidiasis
      with diabetes (10 isolates), and patients with oral candidiasis without diabetes
      (25 isolates). STUDY DESIGN: After incubation, the supernatants and pellets of
      the isolates were used for the enzymatic assays and quantification of colony
      forming units (CFU), respectively. Colorimetric tests were used with
      phosphatidylcholine as a substrate for PL and azocasein as a substrate for SAP,
      and the absorbances of the samples were measured. Enzymatic rates were
      calculated, and values were normalized by CFU. Results were analyzed with
      factorial analyses of variance (alpha = .05). RESULTS: C tropicalis and C
      glabrata were proteolytic and phospholipolytic. The clinical sources of isolates
      had no significant effect on the enzymatic activities (P > .05). C tropicalis had
      significantly higher enzymatic activity for both PL and SAP (P < .001) than did C
      glabrata. CONCLUSIONS: C tropicalis isolates produced significantly higher
      amounts of both enzymes than did the C glabrata isolates.

PMID- 24908599
TI  - Functional toll-like receptor 3 expressed by oral squamous cell carcinoma induced
      cell apoptosis and decreased migration.
AB  - OBJECTIVE: The aim of this study was to investigate the expression and function
      of toll-like receptor 3 (TLR3) in oral squamous cell carcinoma (OSCC). STUDY
      DESIGN: We first assessed TLR3 expression in 20 cases of primary OSCC tissue. Two
      OSCC cell lines, SCC4 and CAL27, were used for further study. Lyophilized
      polyinosinic-polycytidylic acid [Poly(I:C)] was used to activate TLR3 expressed
      by OSCC. Changes in cytokines expression, cell viability, apoptosis, and
      migration in OSCC were investigated. RESULTS: TLR3 was present in both OSCC
      tissue and the 2 OSCC cell lines examined. Poly(I:C) stimulated robust responses
      in OSCC: it upregulated cytokine expression; decreased cell viability by
      suppressing cell proliferation and inducing apoptosis; and decreased cell
      migration. Poly(I:C)-TLR3-induced OSCC cell apoptosis was caspase-3-dependent.
      CONCLUSIONS: The present study indicated that TLR3 might affect OSCC development
      and should be considered as a potential target for future OSCC immunotherapy.

PMID- 24908600
TI  - A new type of dental anomaly: molar-incisor malformation (MIM).
AB  - A molar-incisor malformation (MIM) is a newly discovered type of dental anomaly
      of the permanent first molars, deciduous second molars, and permanent maxillary
      central incisors. MIM anomalies of the permanent first molars and deciduous
      second molars may include normal crowns with a constricted cervical region and
      thin, narrow, and short roots, whereas the affected maxillary central incisors
      may exhibit a hypoplastic enamel notch near the cervical third of the clinical
      crown. Although the etiology of MIM remains to be determined, it is thought to be
      attributable to an epigenetic factor linked to brain- and central nervous system
      related systemic diseases at around age 1 to 2 years. MIM teeth are associated
      with clinical problems such as impaction, early exfoliation, space loss,
      spontaneous pain, periapical abscess, and poor incisor esthetics. Children with
      MIM teeth should be observed closely with respect to their medical history, and
      dentists should formulate a wider-ranging treatment plan.

PMID- 24908601
TI  - Combined mutational analysis of RAS, BRAF, PIK3CA, and TP53 genes in Taiwanese
      patients with oral squamous cell carcinoma.
AB  - OBJECTIVE: Many genetic factors have been implicated in the development of oral
      squamous cell carcinoma (OSCC). Although mutations associated with OSCC have been
      well documented, the rate of these mutations is known to vary by location. The
      goal of this study was to determine the frequency of RAS, BRAF, PIK3CA, and TP53
      mutations in OSCC within the Taiwanese population. STUDY DESIGN: A total of 79
      OSCC tissue specimens were screened for the presence of RAS, BRAF, PIK3CA, and
      TP53 mutations. RESULTS: Missense mutations in HRAS were found in 10 of 79 cases
      (12.66%), and were significantly associated with tumor grade. PIK3CA mutations
      were observed in 11 of 79 cases (13.92%), including a rare mutation, Q546 P, that
      had not previously been reported in OSCC. TP53 mutations were observed in 26 of
      79 patients (32.91%) and were significantly correlated with poor survival.
      CONCLUSIONS: The results suggest that HRAS, PIK3CA, and TP53 may play a role in
      OSCC tumorigenesis.

PMID- 24908602
TI  - Next-generation sequencing analysis for detecting human papillomavirus in oral
      verrucous carcinoma.
AB  - OBJECTIVE: The etiology of oral verrucous carcinoma is unknown, and human
      papillomavirus 'involvement' remains contentious. The uncertainty can be
      attributed to varied detection procedures and difficulties in defining 'gold
      standard' histologic criteria for diagnosing 'verrucous' lesions. Their paucity
      also hampers investigation. We aimed to analyze oral verrucous lesions for human
      papillomavirus (HPV) subtype genomes. STUDY DESIGN: We used next-generation
      sequencing for the detection of papillomavirus sequences, identifying subtypes
      and computing viral loads. We identified a total of 78 oral verrucous cases (62
      carcinomas and 16 hyperplasias). DNA was extracted from all and sequenced at a
      coverage between 2.5% and 13%. RESULTS: An HPV-16 sequence was detected in 1
      carcinoma and 1 hyperplasia, and an HPV-2 sequence was detected in 1 carcinoma
      out of the 78 cases, with viral loads of 2.24, 8.16, and 0.33 viral genomes per
      cell, respectively. CONCLUSIONS: Our results indicate no conclusive human
      papillomavirus involvement in oral verrucous carcinoma or hyperplasia.

PMID- 24908603
TI  - In vivo reproducibility study of ultrasound for monitoring enamel thickness.
AB  - OBJECTIVE: This work assesses ultrasound's reproducibility for monitoring enamel
      thickness in vivo. STUDY DESIGN: This clinical reproducibility study recruited 30
      healthy consenting volunteers. The enamel thickness on an intact maxillary
      central incisor was evaluated at 3 sites on 3 separate visits, 1 week apart.
      Bland-Altman statistical test and intraclass coefficients (ICC) were used to
      assess reproducibility. RESULTS: Reproducibility results were highest for the
      cervical site (bias [mm] = -0.01; 95% limits of agreement = -0.05, 0.04),
      followed by midbuccal (bias = 0.01; 95% limits of agreement = -0.04, 0.06) and
      incisal site (bias = 0; 95% limits of agreement = -0.25, 0.25). ICC was highest
      for the cervical site (0.96) followed by midbuccal (0.71). CONCLUSIONS:
      Ultrasound is a sufficiently reproducible and reliable technique for monitoring
      change in enamel thickness, as in erosive tooth surface loss (TSL). The preferred
      sites for ultrasonographic measurements are cervical and midbuccal.

PMID- 24908604
TI  - Comparison of consumer grade, tablet and 6MP-displays: observer performance in
      detection of anatomical and pathological structures in panoramic radiographs.
AB  - OBJECTIVE: To compare observer performance in the detection of anatomical
      structures and pathology in panoramic radiographs using a consumer grade display
      and tablet (3(rd) generation iPad; Cupertino, CA, USA) under suboptimal
      conditions compared to 6 MegaPixels (6 MP) display under dim lighting conditions.
      STUDY DESIGN: Thirty panoramic radiographs were selected. All images were blindly
      evaluated on three displays by two observers with different amounts of
      experience. Consumer grade display and tablet evaluations were made under
      approximately 510 lx ambient light and 6MP display evaluations under approx. 16
      lx. RESULTS: The observer performance of an experienced observer did not differ
      between different displays whereas the less experienced observer performed better
      with 6MP display than with consumer grade display or tablet. CONCLUSIONS: A
      dentist with less experience in interpreting panoramic radiographs may be more
      dependent on the high-quality display used under optimal viewing conditions to
      detect anatomical structures and pathology compared to a more experienced
      dentist.

PMID- 24908605
TI  - Spontaneous osteosarcoma in craniomaxillofacial fibrous dysplasia: clinical and
      computed tomographic features in 8 cases.
AB  - OBJECTIVE: The aim of this study was to evaluate the patient demographic and
      computed tomography (CT) imaging findings of spontaneous osteosarcoma in
      craniomaxillofacial fibrous dysplasia. STUDY DESIGN: Ten cases of spontaneous
      osteosarcoma in craniomaxillofacial fibrous dysplasia diagnosed during 1993-2013
      were reviewed. Eight cases with CT images were reviewed. RESULTS: The mean age of
      diagnosis of osteosarcoma was 37.8 years (range, 8-55 years). The presence of a
      soft tissue extension component beyond the area of cortical bone destruction was
      demonstrated radiographically in 7 out of 8 cases. Mineralization of tumor matrix
      was seen in 6 cases. Periosteal reaction was demonstrated in only 1 case; 1 out
      of 6 cases showed significant enhancement on postcontrast CT images. Nine
      patients had surgical resections of tumor. Seven of them died of tumor, with a
      mean survival time of 5.3 years. CONCLUSIONS: This study provides CT imaging
      features with clinical information of spontaneous osteosarcoma in
      craniomaxillofacial fibrous dysplasia.

PMID- 24908606
TI  - Evaluation of aeration pretreatment to prepare an inoculum for the two-stage
      hydrogen and methane production process.
AB  - This study evaluates the effect of aeration pretreatment to prepare an inoculum
      for H2 and CH4 production in a two-stage process. Moreover, the biochemical
      hydrogen potential and biochemical methane potential of waste from the food
      industry in a two-stage process was assessed. The results confirmed the
      possibility of using an aerobic stress for selecting a hydrogen-producing
      inoculum. The inoculum was fairly stable since no hydrogenotrophic-methanogenic
      activity was observed in 25 days. The yields measured using glucose as substrate
      were of approximately 160 and 280 N mL(H2) g(COD-1) of glucose for hydrogen and
      methane, respectively, which are in agreement with other studies using heat-shock
      for the pretreatment of the inoculum. When waste of the food industry (wheat
      milling) was used as substrate, a lower H2 yield was achieved by the aerobically
      pretreated inoculum if compared to heat-shock; however, when combined with
      methane production in a two-stage process, much higher CH4 yield was achieved.

PMID- 24908607
TI  - Chronic impact of sulfamethoxazole on acetate utilization kinetics and population
      dynamics of fast growing microbial culture.
AB  - The study evaluated the chronic impact of sulfamethoxazole on metabolic
      activities of fast growing microbial culture. It focused on changes induced on
      utilization kinetics of acetate and composition of the microbial community. The
      experiments involved a fill and draw reactor, fed with acetate and continuous
      sulfamethoxazole dosing of 50 mg/L. The evaluation relied on model evaluation of
      the oxygen uptake rate profiles, with parallel assessment of microbial community
      structure by 454-pyrosequencing. Continuous sulfamethoxazole dosing inflicted a
      retardation effect on acetate utilization in a way commonly interpreted as
      competitive inhibition, blocked substrate storage and accelerated endogenous
      respiration. A fraction of acetate was utilized at a much lower rate with partial
      biodegradation of sulfamethoxazole. Results of pyrosequencing with a replacement
      mechanism within a richer more diversified microbial culture, through
      inactivation of vulnerable fractions in favor of species resistant to antibiotic,
      which made them capable of surviving and competing even with a slower metabolic
      response.

PMID- 24908608
TI  - Naphthyridinone (NTD) integrase inhibitors 4. Investigating N1 acetamide
      substituent effects with C3 amide groups.
AB  - A series of N1 acetamide substituted naphthyridinone HIV-1 integrase inhibitors
      have been explored to understand structure-activity relationships (SAR) with
      various C3 amide groups. Investigations were evaluated using integrase enzyme
      inhibition, antiviral activity and protein binding effects to optimize the sub
      structures. Lipophilicity was also incorporated to understand ligand lipophilic
      efficiency as a function of the structural modifications. Three representative
      analogs were further examined in a peripheral blood mononuclear cell (PBMC)
      antiviral assay as well as in vitro and in vivo drug metabolism and
      pharmacokinetic studies. 

PMID- 24908609
TI  - Synthesis and biological evaluation of novel trichodermin derivatives as
      antifungal agents.
AB  - To discover more potential antifungal agents, 17 novel trichodermin derivatives
      were designed and synthesized by modification of 3 and 4a. The structures of all
      the synthesized compounds were confirmed by (1)H NMR, ESI-MS and HRMS. Their
      antifungal activities against Ustilaginoidea oryzae and Pyricularia oryzae were
      evaluated. Most of the target compounds showed potent inhibitory activity, in
      which 4g showed superior inhibitory effects than 4a and commercial fungicide
      prochloraz. Furthermore, 4h demonstrated comparable inhibitory activity to 4a.
      Moreover, 4i and 4l exhibited excellent inhibitory activity for Pyricularia
      oryzae. Additionally, compound 9 was found to be more active against all tested
      fungal strains than 3, with EC50 values of 0.47 and 3.71 mg L(-1), respectively.

PMID- 24908610
TI  - Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity.
AB  - A series of 9-alkylaminoacridines were synthesized and evaluated for activity
      against two strains of methicillin-resistant and one strain of methicillin
      sensitive Staphylococcus aureus. Results are presented that show a clear
      structure activity relationship between the N-alkyl chain length and
      antibacterial activity with peak MIC99 values of 2-3 MUM for alkyl chains ranging
      from 10 to 14 carbons in length. Although prior work has linked the function of
      acridine-based compounds to intercalation and topoisomerase inhibition, the
      present results show that 9-alkylaminoacridines likely function as amphiphilic
      membrane-active disruptors potentially in a similar manner as quaternary ammonium
      antimicrobials.

PMID- 24908611
TI  - Bedtime problems and night wakings in young children: an update of the evidence.
AB  - Bedtime problems and night wakings in infants and young children are prevalent,
      persistent, and associated with a variety of impairments in youth and their
      families. Assessment strategies include clinical interview, sleep diaries,
      actigraphy, and subjective measures. A number of treatment approaches with
      varying degrees of empirical support are available, and several novel strategies
      have been evaluated in recent years. Appropriate sleep scheduling and a bedtime
      routine are important components of any treatment program. 

PMID- 24908613
TI  - A single-stage biological process for municipal sewage treatment in tourist
      areas.
AB  - This pilot scale study aims to test the effectiveness of an innovative compact
      biological system (SBBGR - Sequencing Batch Biofilter Granular Reactor) for
      treating municipal wastewater in tourist areas characterised by intense seasonal
      water demand and wastewater discharge. The results obtained after a long term
      operation of 463 days have shown that the proposed system is able to assure
      average removal efficiencies higher than 90% for COD (chemical oxygen demand),
      total suspended solids and TKN (total Kjeldahl nitrogen) independently of the
      influent concentration values and organic loading, which ranged from 0.2 to 5.1
      kgCOD/m(3)biofilter.d Furthermore, the plant showed a high degree of operation
      flexibility and stability in response to the organic load variations occurring in
      tourist areas. In fact, no significant deterioration in the plant's effluent
      quality was observed even during a sudden several-fold increase in organic
      loading. High nitrogen removal efficiencies (80%, on average) were also achieved
      thanks to the establishment of simultaneous nitrification-denitrification process
      favoured by the plant's high biomass concentration and operating conditions.
      Finally, the system was characterized by an excess sludge production much lower
      (60-80% lower) than that of conventional biological systems operating without a
      primary clarifier. An acceptable level of stabilization of excess sludge was also
      obtained so that a further stabilization process was no longer required. 

PMID- 24908612
TI  - Modelling available crown fuel for Pinus pinaster Ait. stands in the "Cazorla,
      Segura and Las Villas Natural Park" (Spain).
AB  - One of the main limiting aspects in the application of crown fire models at
      landscape scale has been the uncertainty derived to describe canopy fuel stratum.
      Available crown fuel and canopy bulk density are essential in order to simulate
      crown fire behaviour and are of potential use in the evaluation of silvicultural
      treatments. Currently, the more accurate approach to estimate these parameters is
      to develop allometric models from common stand inventory data. In this sense,
      maritime pine (Pinus pinaster Aiton) trees were destructively sampled in the
      South of the Iberian Peninsula, covering natural and artificial stands. Crown
      fine fuel was separated into size classes and allometric equations that estimate
      crown fuel load by biomass fractions were developed. Available crown fuel was
      determined according to the fuel load differences between un-burned and burned
      trees with similar characteristics. Taking our destructive post-fire inventory
      into account, available crown fuel was estimated as the sum of needles biomass,
      87.63% of the twigs biomass and 62.79% of the fine branches biomass. In spite of
      the differences between natural and artificial stands, generic models explained
      82% (needles biomass), 89% (crown fuel), 92% (available crown fuel) and 94%
      (canopy bulk density) of the observed variation. Inclusion of the fitted models
      in fire management decision-making can provide a decision support system for
      assessing the potential crown fire of different silvicultural alternatives. 

PMID- 24908614
TI  - Simultaneous removal of oil and grease, and heavy metals from artificial bilge
      water using electro-coagulation/flotation.
AB  - US and international regulations pertaining to the control of bilge water
      discharges from ships have concentrated their attention to the levels of oil and
      grease rather than to the heavy metal concentrations. The consensus is that any
      discharge of bilge water (and oily water emulsion within 12 nautical miles from
      the nearest land cannot exceed 15 parts per million (ppm). Since there is no
      specific regulation for metal pollutants under the bilge water section, reference
      standards regulating heavy metal concentrations are taken from the ambient water
      quality criteria to protect aquatic life. The research herein presented discusses
      electro-coagulation (EC) as a method to treat bilge water, with a focus on oily
      emulsions and heavy metals (copper, nickel and zinc) removal efficiency.
      Experiments were run using a continuous flow reactor, manufactured by Ecolotron,
      Inc., and a synthetic emulsion as artificial bilge water. The synthetic emulsion
      contained 5000 mg/L of oil and grease, 5 mg/L of copper, 1.5 mg/L of nickel, and
      2.5 mg/l of zinc. The experimental results demonstrate that EC is very efficient
      in removing oil and grease. For oil and grease removal, the best treatment and
      cost efficiency was obtained when using a combination of carbon steel and
      aluminum electrodes, at a detention time less than one minute, a flow rate of 1
      L/min and 0.6 A/cm(2) of current density. The final effluent oil and grease
      concentration, before filtration, was always less than 10 mg/L. For heavy metal
      removal, the combination of aluminum and carbon steel electrodes, flow rate of 1
      L/min, effluent recycling, and 7.5 amps produced 99% zinc removal efficiency.
      Copper and nickel are harder to remove, and a removal efficiency of 70% was
      achieved. 

PMID- 24908615
TI  - [X-ray pelvimetry practice survey in Northeast French maternities].
AB  - OBJECTIVE: To describe and compare the indications and modalities of X-ray
      pelvimetry in obstetrical practice in the Northeast French maternities. MATERIALS
      AND METHODS: An anonymous questionnaire was sent to the heads of obstetric
      departments in the Northeast French maternities. The questionnaire was built
      around four issues: description of the hospital characteristics, assessment of
      the obstetrical prognosis (modalities of delivery), indications and modalities of
      X-ray pelvimetry. RESULTS: The response rate was 47%. The evaluation of the
      obstetrical prognosis was performed in 77% of maternities. Indications were:
      breech presentation (86%), suspicion of fetal-pelvic disproportion (78%), mother
      size lesser than 150cm (64%) and previous caesarean section (42%). Pelvic
      computed tomography was performed in the majority of the maternities (94%),
      between 35 and 37 weeks of amenorrhea (47%). Level III maternities and
      maternities with more than 2000 deliveries per year seemed to observe fewer
      indications than other maternities, but these indications were still globally
      excessive, comparing with the College national des gynecologues et obstetriciens
      francais' recommendations. CONCLUSION: These results should lead professionals to
      develop an assessment of their practices about the indications of X-ray
      pelvimetry.

PMID- 24908617
TI  - 3D-microleakage assessment of adhesive interfaces: exploratory findings by MUCT.
AB  - OBJECTIVES: To explore the feasibility of a 3D-microleakage protocol for the
      evaluation of various configurations of adhesive-tooth interfaces. METHODS: Three
      different kinds of specimens were prepared: (1) a Class-I composite restoration
      placed without any bonding to maximize gap formation at the interface; (2) a
      glass-fiber post cemented with a self-adhesive composite cement into a prepared
      root canal; and (3) inlay MOD composite restorations placed with either a 1-step
      self-adhesive or a 2-step etch-and-rinse composite cement. After silver-nitrate
      (AgNO3) infiltration, the specimens were scanned using a Skyscan 1172 X-ray
      microtomograph (MUCT; Skyscan Bruker) at 100kV, 100MUA and 7.8-9.5MUm resolution.
      Projection images were reconstructed, after which maximum-intensity projections
      (MIPs) and 3D-volumetric renderings were produced. For the inlays, an additional
      conventional stereomicroscopic (SM) microleakage evaluation was accomplished
      after specimen sectioning. RESULTS: MIPs and 3D-renderings from specimens (1) and
      (2) revealed strongly varying microleakage patterns along the marginal
      gap/interface. For the specimens of setup (3), the high radiopacity of the 2-step
      composite cement hindered evaluation of the MIPs. MIP-microleakage patterns along
      the enamel margin of the restoration cemented with the 1-step composite cement
      corresponded well to the stereomicroscopic images. SIGNIFICANCE: The reported
      MUCT-protocol revealed good sensitivity to detect AgNO3 infiltration at the
      adhesive-tooth interface when considerable microleakage was present. When
      microleakage was less apparent and spread in a more diffuse pattern, evaluation
      with MUCT was less sensitive compared to stereomicroscopic evaluation.

PMID- 24908616
TI  - The role of BMPs in endothelial cell function and dysfunction.
AB  - The bone morphogenetic protein (BMP) family of proteins has a multitude of roles
      throughout the body. In embryonic development, BMPs promote endothelial
      specification and subsequent venous differentiation. The BMP pathway also plays
      important roles in the adult vascular endothelium, promoting angiogenesis and
      mediating shear and oxidative stress. The canonical BMP pathway functions through
      the Smad transcription factors; however, other intracellular signaling cascades
      can be activated, and receptor complexes beyond the traditional type I and type
      II receptors add additional layers of regulation. Dysregulated BMP signaling has
      been linked to vascular diseases including pulmonary hypertension and
      atherosclerosis. This review addresses recent advances in the roles of BMP
      signaling in the endothelium and how BMPs affect endothelial dysfunction and
      human disease. 

PMID- 24908618
TI  - Intractable ventricular fibrillation: post ascending aortic dissection repair.
AB  - Ascending aortic dissection is a life threatening surgical emergency and carries
      high peri-operative mortality. Various biological adhesive materials are commonly
      used in such a surgery to enhance strengthening of separated layers of aortic
      wall. Despite of extensive use, embolization of the glue material remains a
      feared complication. Here we are describing a case where BioGlue embolized down
      the left main stem and resulted in refractory ventricular arrhythmia and
      hemodynamic instability. 

PMID- 24908619
TI  - Combined percutaneous balloon mitral valvuloplasty and left atrial appendage
      occlusion device implantation for rheumatic mitral stenosis and atrial
      fibrillation.
AB  - Rheumatic heart disease is a common cause of cardiovascular morbidity and
      mortality worldwide, mostly in developing countries. Mitral stenosis and atrial
      fibrillation often coexist, related to both structural and inflammatory changes
      of the mitral valve and left atrium. Both predispose to left atrial thrombus
      formation, commonly involving the left atrial appendage. Thromboembolism can
      occur, with devastating consequences. We report the case of a 62 year old woman
      with rheumatic heart disease resulting in mitral stenosis and atrial
      fibrillation. Previous treatment with warfarin resulted in life-threatening
      gastrointestinal bleeding and she refused further anticoagulant therapy. A
      combined procedure was performed, including percutaneous balloon mitral
      valvuloplasty and left atrial appendage occlusion device implantation with the
      Atritech(r) Watchman(r) device. No thromboembolic or bleeding complications were
      encountered at one year follow-up. Long-term follow-up in a cohort of patients
      will be required to evaluate the safety and efficacy of this strategy. 

PMID- 24908620
TI  - The influence of adjunctive treatment and metacognitive deficits in schizophrenia
      on the experience of work.
AB  - Enhancing work function is now widely considered a core element of comprehensive
      schizophrenia treatment. While research efforts have illuminated factors that
      influence how well patients perform at work, less is known about the factors
      influencing the subjective experience of work. It is not known how, and to what
      extent, symptoms, cognitive deficits or metacognitive capacities impact job
      satisfaction and whether treatment can have an effect on job satisfaction. To
      explore this issue, data from a trial in which participants in a six-month
      vocational program were assigned to either a standard support group or a
      cognitive behavioral group therapy, and asked to fill in weekly self-reports of
      job satisfaction was analyzed. Work satisfaction and the consistency of these
      ratings were compared between the two groups and the moderating influence of
      metacognitive capacity was analyzed. A significant interaction effect revealed
      that higher metacognitive capacity predicted higher average job satisfaction only
      in the CBT group. Additionally, higher metacognitive capacity led to a more
      varied appraisal of work satisfaction only in the support group. 

PMID- 24908621
TI  - Fifteenth International Congress on Neutron Capture Therapy. Preface.

PMID- 24908622
TI  - [Conglomerate silicosis in a sandblasting worker].

PMID- 24908623
TI  - [Acute cutaneous pustular eruption due to hydroxychloroquine].

PMID- 24908624
TI  - [Management of vascular risk factors in patients older than 80].
AB  - The number of patients older than 80 years is steadily increasing and it
      represents the main basis for increasing population figures in developed
      countries. Cardiovascular diseases are the leading causes of mortality and
      disability causes result in a huge burden of disease in elderly people. However,
      available scientific evidence to support decision-making on cardiovascular
      prevention in elderly patients is scarce. Currently available risk assessment
      scales cannot be applied to elderly people. They are focused on cardiovascular
      mortality risk and do not provide information on factors with a proven prognostic
      value in the very old (functioning disability, dementia). Elderly people are a
      highly heterogeneous population, with a variety of co-morbidities, as well as
      several functional and cognitive impairment degrees. Furthermore, aging
      associated physiological changes and common use of multiple drugs result in an
      increased risk of adverse drug reactions. Thus, drug use should always be based
      on a risk/benefit assessment in the elderly. Therefore, therapeutic decision
      making in the very old must be an individually tailored and based on an
      appropriate clinical judgement and a comprehensive geriatric assessment. The
      current consensus report aims to present a proposal for clinical practices in the
      primary and secondary cardiovascular prevention in the very old and to provide a
      number of recommendations on lifestyle changes and drug therapy for the
      management of major cardiovascular risk factors. 

PMID- 24908625
TI  - Is ultrasound screening reliable for adverse local tissue reaction after hip
      arthroplasty?
AB  - There is increasing awareness of prevalence of adverse local tissue reaction
      (ALTR) surrounding metal-on-metal (MoM) and highly cross-linked polyethylene
      (HXLPE) bearings, and sensitive and simple screening modalities for ALTR are
      required. We examined reliability of ultrasound screening for ALTR in 131 hips of
      105 patients who received both ultrasound and MRI examinations after hip
      arthroplasty with MoM or HXLPE bearings. Using the MRI results as reference,
      sensitivity, specificity and accuracy of ultrasound were 74%, 92% and 84% around
      MoM bearings, and 90%, 83%, and 85% around HXLPE bearings. Ultrasound detected
      ALTR in 11 hips that were not shown with MRI. Ultrasound examination is assumed
      to be a reliable screening tool for detecting clinically important ALTR lesions
      developing in the anterior region around MoM or HXLPE bearings.

PMID- 24908626
TI  - Proximal humerus fractures: is there more than one way to skin a cat?

PMID- 24908627
TI  - A pre-clinical evaluation of silver, iodine and Manuka honey based dressings in a
      model of traumatic extremity wounds contaminated with Staphylococcus aureus.
AB  - Prevention of extremity war wound infection remains a clinical challenge.
      Staphylococcus aureus is the most common pathogen in delayed infection. We
      hypothesised that choice of wound dressings may affect bacterial burden over 7
      days reflecting the current practice of delayed primary closure of wounds within
      this timeframe. A randomised controlled trial of 3 commercially available
      dressings (Inadine((r)) (Johnson & Johnson, NJ, USA), Acticoat((r)) (Smith &
      Nephew, Hull, UK), Activon Tulle (Advancis Medical, Nottingham, UK)) was
      conducted in a rabbit model of contaminated forelimb muscle injury. A positive
      control group treated with antibiotics was included. Groups were compared to a
      saline soaked gauze control. The primary outcome was a statistically significant
      reduction (p < 0.05) in tissue S. aureus at 7 days post-injury. Secondary outcome
      measurements included bacteraemias, observational data, whole blood
      determination, ELISA for plasma biomarkers, PCR array analysis of wound healing
      gene expression and muscle/lymph node histopathology. Antibiotic, Inadine and
      Acticoat groups had statistically significant lower bacterial counts (mean 7.13
      [95% CI 0.00-96.31]*10(2); 1.66 [0.94-2.58]*10(5); 8.86 [0.00-53.35]*10(4)cfu/g,
      respectively) and Activon Tulle group had significantly higher counts (2.82 [0.98
      5.61]*10(6)cfu/g) than saline soaked gauze control (7.58 [1.65
      17.83]*10(5)cfu/g). There were no bacteraemias or significant differences in
      observational data or whole blood determination. There were no significant
      differences in muscle/loss or pathology and lymph node cross-sectional area or
      morphology. There were some significant differences between treatment groups in
      the plasma cytokines IL-4, TNFalpha and MCP-1 in comparison to the control. PCR
      array data demonstrated more general changes in gene expression in the muscle
      tissue from the Activon Tulle group than the Inadine or Acticoat dressings with a
      limited number of genes showing significantly altered expression compared to
      control. This study has demonstrated that both Acticoat((r)) and Inadine((r))
      dressings can reduce the bacteria burden in a heavily contaminated soft tissue
      wound and so they may offer utility in the clinical setting particularly where
      surgical treatment is delayed.

PMID- 24908628
TI  - The spectrum and outcome of pregnant trauma patients in a metropolitan trauma
      service in South Africa.
AB  - INTRODUCTION: Pregnant patients involved in trauma pose unique diagnostic and
      treatment challenges as the physiological and anatomical changes associated with
      pregnancy, and the need to preserve foetal well-being, result in a number of
      nuances in the standard resuscitation algorithms. This clinical audit within a
      busy developing world trauma service describes the spectrum and outcome of
      pregnant trauma patients. METHODS: All pregnant patients presenting to the
      Pietermaritzburg Metropolitan Hospital Complex following trauma were included in
      the study. Data were retrieved from the trauma registry and analyzed using
      descriptive statistics on a spreadsheet. The study ran from the 1st of July 2011
      to the 31st of December 2013. RESULTS: During the study period, 1075 female
      trauma patients were admitted, with a 4% incidence of pregnant patients
      (42/1075). The mean age of the patients in the study was 24.9 years with an
      average age of gestation of 21.4 weeks. Blunt trauma accounted for the majority
      of injuries (57%). Trauma was by way of intentional assault in 52% of the cases.
      Of the cases of assault, 81% of the time, the assailant was known to the victim
      and in the majority of cases (55%) the assailant was the patient's intimate
      partner. Polytrauma predominated as the most common pattern of injury. Foetal
      death occurred in more than a third of cases (15/42). In 90% of the patients with
      an Injury Severity Score greater than fifteen, there was foetal death. Eighty-six
      percent (6/7) of the patients who required surgery had an unfavourable foetal
      outcome. In 73% of the cases of foetal death, the pregnancies were less than 28
      weeks gestation. CONCLUSION: In an environment with high rates of interpersonal
      violence, trauma in pregnancy is not an uncommon occurrence. It is most commonly
      due to assault and the assailant is known to the victim in the majority of cases.
      Blunt trauma still predominates in this setting but there is a high incidence of
      penetrating trauma. Foetal mortality in this group is high and reflects the
      severity of the trauma experienced.

PMID- 24908629
TI  - [Reconstruction of an abdominal wall defect with a superior epigastric perforator
      propeller flap: case report].
AB  - Perforators flaps take a special place in reconstructive surgery. These flaps can
      be dissected and turned as a propeller blade on its pedicule axis. We report the
      case of a 54-year-old man presenting a recurrence of a dermatofibrosarcoma in the
      right hypochondrium. Tumor resection caused a large abdominal wall defect taking
      the anterior aponeurosis of the rectus abdominis. An angioscanner was realized in
      preoperative to locate the perforators of the deep superior epigastric artery. We
      realized a propeller flap based on a perforator of the left superior epigastric
      artery who allowed to cover the wall defect. We set up a patch of Vicryl(r) to
      reconstruct the aponeurosis plan at the same operative time. We didn't note any
      necrosis and complete healing occurred in 2 weeks. The margins were healthy. The
      cosmetic result and the low morbidity make this flap a good therapeutic option.
      This flap seems reliable, arteries perforators are constant with good diameter.

PMID- 24908630
TI  - The PD-1/PD-Ls pathway and autoimmune diseases.
AB  - The programmed death (PD)-1/PD-1 ligands (PD-Ls) pathway, is a new member of the
      B7/CD28 family, and consists of the PD-1 receptor and its ligands PD-L1 (B7-H1,
      CD274) and PD-L2 (B7-DC, CD273). Recently, it is reported that PD-1, PD-L1 and PD
      L2 also have soluble forms aside from their membrane bound forms. The soluble
      forms increase the diversity and complexity of PD-1/PD-Ls pathway in both
      composition and function. The PD-1/PD-Ls pathway is broadly expressed and exerts
      a wider range of immunoregulatory roles in T-cell activation and tolerance
      compared with other B7/CD28 family members. Studies show that the PD-1/PD-Ls
      pathway regulates the induction and maintenance of peripheral tolerance and
      protects tissues from autoimmune attack in physiological conditions. In addition,
      it is also involved in various diseases mediated by T cells, such as
      autoimmunity, tumor immunity, chronic viral infections, and transplantation
      immunity. In this review, we will summarize the relevance of the soluble forms
      and the latest researches on the role of PD-1/PD-Ls pathway in autoimmune
      diseases.

PMID- 24908631
TI  - Health care delivery in type 2 diabetes. A survey in an Italian primary care
      practice.
AB  - AIMS: Evidence-based guidelines provide targets and performance measures for the
      treatment of type 2 diabetic patients but a wide gap separates guidelines-driven
      recommendations from their clinical application, a phenomenon hindering the
      transfer of proven benefits to affected populations. METHODS: We analyzed the
      quality of diabetic care delivered by 8 general practitioners joint in a group
      practice attending 571 diabetic patients (5.6% of the total enlisted subjects) by
      assessing process (% of HbA1c, SBP and LDL-C determinations) and intermediate
      outcome (% of patients with HbA1c <7% vs >8%, systolic BP <130 mmHg vs >140 mmHg,
      LDL-cholesterol <100 mg/dL vs >130 mg/dL) indicators. RESULTS: HbA1c was at
      target in 49% of patients and >8% in 22%; SBP and LDL-C determination was
      available in about two-thirds of patients, only a minority at target for SBP and
      LDL-C. Antihyperglycemic and antihypertensive treatment was prescribed in most
      patients but only a third was on statins. During the post-evaluation phase,
      percentages of patients with HbA1c >8%, SBP < 130 mmHg and LDL-C < 100 mg/dL and
      the drug prescription pattern did not change. CONCLUSIONS: Several weaknesses
      affect primary care delivery to type 2 diabetic patients and efforts are needed
      to improve the management of this high-risk group.

PMID- 24908632
TI  - [Drug-induced immune hemolytic anemia: a retrospective study of 10 cases].
AB  - PURPOSE: Drug-induced immune haemolytic anemia occurs in one case per million and
      can be fatal. Our aim was to describe the main characteristics and the type of
      drug involved. METHODS: Cases were retrospectively identified using spontaneous
      notifications collected by our pharmacovigilance centre and the results of immuno
      hematological investigations performed by the laboratory of French blood
      establishment of Lyon between 2000 and 2012. Inclusion criteria were: an immune
      (positive direct antiglobulin test), hemolytic, anemia (haemoglobin <100 g/L),
      with at least a plausible causal relationship with drug exposure according to the
      French method of imputability or the presence of drug-dependent antibodies, and
      exclusion of other causes of hemolysis. RESULTS: Ten cases (5 men and 5 women,
      median age 54.4 years) were identified. Causal drugs were ambroxol, beta
      interferon, cefotetan, ceftriaxone, loratadine, oxacillin, oxaliplatine,
      piperacillin-tazobactam, pristinamycin, and quinine. The median time to onset of
      anemia after starting the culprit drug was 6 days (2 hours to 16 days). The
      median nadir of hemoglobin was 57.9 g/L (range: 34-78). The direct antiglobulin
      test was positive in 8 patients: IgG only (n=4), IgG and complement (n=3), and
      IgA (n=1). Drug-induced immune haemolytic anemia was considered as definite in 5
      cases with positive drug-induced antibodies, probable in 4 cases negative for the
      detection of drug-induced antibodies but with plausible or likely causal
      relationship with drug exposure, and probable with an autoimmune mechanism in 1
      case. CONCLUSION: The diagnosis of DIIHA is often difficult because of the
      similarities with autoimmune haemolytic anemia and the inconstant sensitivity of
      immunologic tests that sometimes required repetitive assessment.

PMID- 24908633
TI  - Expanding the Mimiviridae family using asparagine synthase as a sequence bait.
AB  - Since the pioneering Global Ocean Sampling project, large-scale sequencing of
      environmental DNA has become a common approach to assess the biodiversity of
      diverse environments, with an emphasis on microbial populations: unicellular
      eukaryotes ("protists"), bacteria, archaea, and their innumerous associated
      viruses and phages. However, the global analysis of the viral diversity ("the
      virome") from sequence data is fundamentally hampered by the lack of a universal
      gene that would allow their unambiguous identification and reliable separation
      from cellular microorganisms. The problem has been made even more difficult with
      the discovery of micron-sized giant viruses for which the usual fractionation
      protocol on a "sterilizing" filter is no longer an option. In the present proof
      of-principle work we used actual metagenomic data to show that glutamine
      hydrolysing asparagine synthase is a reliable sequence probe to discover new
      members of the Mimiviridae family, hint at the existence of a new family of large
      DNA viruses, and point out misidentified database entries. 

PMID- 24908634
TI  - Radiotherapy for glomus jugulare paraganglioma.
AB  - Surgery has been long considered to be the treatment of choice for glomus
      jugulare paragangliomas, as it is the only modality able to totally eradicate the
      tumour. However, despite considerable progress in interventional radiology and
      nerve monitoring, surgery is associated with an unacceptably high complication
      rate for a benign tumour, explaining the growing place of radiotherapy in the
      management of these tumours. This review of the literature confirms the efficacy
      of conformal radiotherapy with or without intensity modulation and stereotactic
      radiotherapy, which both achieve tumour control rates ranging from 90% to almost
      100% of cases, but for different tumour volumes, almost constant stabilization or
      even improvement of symptoms, and a considerably lower rate of adverse effects
      than with surgery. However, radiotherapy remains contraindicated in the presence
      of intracranial invasion or extensive osteomyelitis. In the light of these
      results, together with the improved quality of life and a better knowledge of the
      natural history of this disease, many authors propose radiotherapy as first-line
      treatment for all glomus jugulare paragangliomas regardless of their size,
      particularly in patients with no preoperative deficits. 

PMID- 24908635
TI  - Tobacco and otorhinolaryngology: epic and disaster.
AB  - More than 500 papers are retrieved from the PubMed database by the keywords
      "Tobacco" and "Otorhinolaryngology", none of which, however, is devoted to the
      history of a plant that has a major impact on our specialty and practice. The
      present report describes and analyzes how tobacco conquered the world, the
      conflicts it triggered and the impact it has had in our field over the past
      centuries. 

PMID- 24908636
TI  - Association between some endocrine-disrupting chemicals and childhood obesity in
      biological samples of young girls: a cross-sectional study.
AB  - Childhood obesity, a major public health concern, has increased worldwide.
      Endocrine-disrupting chemicals (EDCs) have recently received attention as a cause
      of obesity. A cross-sectional study using logistic regression was conducted to
      investigate the association between some endocrine disrupting chemicals and
      obesity in young girls. Endogenous steroids expected to be associated with EDCs
      were also investigated. The target compounds included 7 phthalates (MEP, DBP,
      MBP, DEHP, MEHP, PA and MBzP), 2 alkylphenols (4-NP and t-OP), bisphenol A and 9
      endogenous steroids (DHT, epi-T, T, DHEA, A, P, E1, E2 and E3). PA in urine and
      MEP, DBP and PA in serum showed statistically significant differences between the
      control and obese groups, those compounds were considered to be associated with
      obesity. In addition, DHEA in serum showed a statistically significant difference
      between obese and control groups. We concluded that these substances can affect
      the development of obesity. 

PMID- 24908637
TI  - Boswellia ovalifoliolata abrogates ROS mediated NF-kappaB activation, causes
      apoptosis and chemosensitization in Triple Negative Breast Cancer cells.
AB  - The present study was aimed to evaluvate the apoptogenic potential of ethanolic
      extract of leaves from Boswellia ovalifoliolata (BL EthOH) and to unravel the
      molecular mechanisms implicated in apoptosis of Triple Negative Breast Cancer
      (TNBC) cells. BL EthOH was cytotoxic against TNBC cells like MDA-MB-231 and MDA
      MB-453 with IC50 concentrations 67.48 +/- 5.45 and 70.03 +/- 4.76 MUg/ml,
      respectively. Apoptotic studies showed that BL EthOH was able to induce apoptosis
      and western blot studies demonstrated that BL EthOH significantly decreased the
      Phospho-NF-kappaB (ser536), PCNA, anti-apoptotic protein Bcl-2 expression and
      increased the expression of pro-apoptotic protein Bax, in MDA-MB-231 and MDA-MB
      453 cell lines when compared with untreated cells. Besides, BL EthOH has
      synergistic chemosensitizing effects on TNBC cells and increased the cytotoxicity
      of doxorubicin and cisplatin.

PMID- 24908638
TI  - Immunoproteomics of Brucella abortus RB51 as candidate antigens in serological
      diagnosis of brucellosis.
AB  - The current brucellosis serodiagnostic assays are chiefly based on detecting anti
      LPS (lipopolysaccharide) antibodies. However, cross-reaction with some gram
      negative bacteria can occasionally induce due to similar O-polysaccharide (OPS)
      structure. Therefore, the aim of the present study was to identify new candidate
      antigens from Brucella abortus RB51, a mutant strain lacking the LPS portion,
      which might be valuable in brucellosis diagnosis. To detect potential antigens,
      immobilized pH gradients (IPG) strips with three ranges (pH 3-5.6, 4-7 and 6-11)
      were applied. After separating the insoluble proteins of B. abortus RB51 using
      two-dimensional electrophoresis (2-DE), their immunogenicity was evaluated by
      western blotting using four types of antisera - B. abortus, Yersinia
      enterocolitica O:9 and Escherichia coli O157:H7-positive, and B. abortus-negative
      bovine sera. Among the several immunogenic spots, the spots showing specific
      reactivity with only the B. abortus-positive antisera, were considered as
      candidate antigens. Overall, eleven immuno-reactive proteins were identified, as
      follows: Cu/Zn superoxide dismutase, histidinol dehydrogenase, chaperonin DnaK,
      chaperonin GroES, beta-ketoadipyl CoA thiolase, two-component response regulator,
      the cell-division protein FtsZ, aldehyde dehydrogenase, 50s ribosomal protein L10
      and invasion protein B. These selected highly immunogenic protein spots might be
      useful as alternative antigens for brucellosis and helpful in reducing the cross
      reactivity. 

PMID- 24908639
TI  - Detection of platelet microRNA expression in patients with diabetes mellitus with
      or without ischemic stroke.
AB  - AIMS: The objective of this study was to investigate the role of plasma and
      platelet microRNAs in the occurrence of ischemic stroke in patients with diabetes
      mellitus. METHODS: miR-223, miR-146a, miR-495, and miR-107 expression in the
      plasma and platelets, blood glucose concentration, and platelet activation rate
      were measured in patients with diabetes mellitus and ischemic stroke, diabetes
      mellitus only, ischemic stroke only, and healthy controls. Platelet activity was
      measured by flow cytometric measurement of P-selectin expression, while miRNA was
      measured by real-time PCR. RESULTS: The expressions of platelet and plasma miR
      223 and miR-146a were significantly downregulated in patients with ischemic
      stroke and diabetes mellitus or diabetes mellitus only, but not in patients with
      ischemic stroke only compared to healthy controls. The expressions of platelet
      and plasma miR-495 and miR-107 showed no significant differences among these four
      groups. The expression of platelet miR-223 and miR-146a significantly correlated
      with plasma miR-223 and miR-146a levels, blood glucose concentration, and
      platelet activation rate. CONCLUSIONS: Hyperglycemia may downregulate the
      expressions of miR-223 and miR-146a, leading to subsequent platelet activation in
      patients with diabetes mellitus. Low platelet and plasma miR-223 and miR-146a
      expression is a risk factor for ischemic stroke in Chinese diabetes mellitus
      patients.

PMID- 24908640
TI  - Coupled circuit numerical analysis of eddy currents in an open MRI system.
AB  - We performed a new coupled circuit numerical simulation of eddy currents in an
      open compact magnetic resonance imaging (MRI) system. Following the coupled
      circuit approach, the conducting structures were divided into subdomains along
      the length (or width) and the thickness, and by implementing coupled circuit
      concepts we have simulated transient responses of eddy currents for subdomains in
      different locations. We implemented the Eigen matrix technique to solve the
      network of coupled differential equations to speed up our simulation program. On
      the other hand, to compute the coupling relations between the biplanar gradient
      coil and any other conducting structure, we implemented the solid angle form of
      Ampere's law. We have also calculated the solid angle for three dimensions to
      compute inductive couplings in any subdomain of the conducting structures.
      Details of the temporal and spatial distribution of the eddy currents were then
      implemented in the secondary magnetic field calculation by the Biot-Savart law.
      In a desktop computer (Programming platform: Wolfram Mathematica 8.0(r),
      Processor: Intel(R) Core(TM)2 Duo E7500 @ 2.93GHz; OS: Windows 7 Professional;
      Memory (RAM): 4.00GB), it took less than 3min to simulate the entire calculation
      of eddy currents and fields, and approximately 6min for X-gradient coil. The
      results are given in the time-space domain for both the direct and the cross
      terms of the eddy current magnetic fields generated by the Z-gradient coil. We
      have also conducted free induction decay (FID) experiments of eddy fields using a
      nuclear magnetic resonance (NMR) probe to verify our simulation results. The
      simulation results were found to be in good agreement with the experimental
      results. In this study we have also conducted simulations for transient and
      spatial responses of secondary magnetic field induced by X-gradient coil. Our
      approach is fast and has much less computational complexity than the conventional
      electromagnetic numerical simulation methods. 

PMID- 24908641
TI  - Drugs of abuse and benzodiazepines in the Madrid Region (Central Spain): seasonal
      variation in river waters, occurrence in tap water and potential environmental
      and human risk.
AB  - This work analyzes the seasonal variation (winter and summer) of ten drugs of
      abuse, six metabolites and three benzodiazepines in surface waters from the
      Jarama and Manzanares Rivers in the Madrid Region, the most densely populated
      area in Spain. The occurrence of these compounds in tap water in this region is
      also investigated and a preliminary human health risk characterization performed
      for those substances found in tap water. Finally, a screening level risk
      assessment that combines the measured environmental concentrations (MECs) with
      dose-response data to estimate Hazard Quotients (HQs) for the compounds studied
      is also presented. The results of this study show the presence of fourteen out of
      the nineteen compounds analyzed in winter and twelve of them in summer. The most
      ubiquitous compounds, with a frequency of detection of 100% in both seasons, were
      the cocaine metabolite benzoylecgonine (BE), the amphetamine-type stimulant (ATS)
      ephedrine (EPH), the opioid methadone (METH), the METH metabolite 2-ethylene-1,5
      dimethyl-3,3-diphenylpyrrolidine (EDDP), and the three benzodiazepines
      investigated, namely alprazolam (ALP), diazepam (DIA) and lorazepam (LOR). The
      highest concentrations observed corresponded to EPH (1020ngL(-1) in winter and
      250ngL(-1) in summer). The only compounds not detected in both seasons were
      heroin (HER) and its metabolite 6-acetylmorphine (6ACM), lysergic acid
      diethylamide (LSD) and its metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD), and Delta(9)
      tetrahydrocannabinol (THC). In terms of overall concentration, all sampling
      points presented higher concentrations in winter than in summer. Statistical
      analyses performed to gather evidence concerning occasional seasonal differences
      in the concentrations of individual substances between summer and winter showed
      statistically significantly higher concentrations (p<0.05) of BE, EPH and the
      opioid morphine (MOR) in winter than in summer. Two out of the nineteen compounds
      studied, namely cocaine (CO) and EPH, were detected in tap water from one
      sampling point at concentrations of 1.61 and 0.29ngL(-1), respectively. The
      preliminary human health risk characterization showed that no toxic effects could
      be expected at the detected concentration level in tap water. The screening level
      risk assessment showed that MOR, EDDP and the THC metabolite 11-nor-9-carboxy
      Delta(9)-tetrahydrocannabinol (THC-COOH) were present in at least one of the
      sampling sites in a concentration leading to a Hazard Quotient (HQ) value between
      1.0 and 10.0, thus indicating some possible adverse effects. The cumulative HQ or
      Toxic units (TUs) calculated for each of the groups studied showed that opioids
      and cannabinoids were present at concentrations high enough to potentially
      generate some adverse effects on at least one sampling point. 

PMID- 24908642
TI  - Association of body burden of mercury with liver function test status in the U.S.
      population.
AB  - The majority of mercury (Hg) exposure in the US population is from consumption of
      fish contaminated with methylmercury (MeHg). Since inorganic Hg is the
      predominant form excreted in the feces and urine, hepatic biotransformation is a
      critical step in its normal clearance. This study was set to test the hypothesis
      that compromised liver function is associated with body burden of Hg as
      indirectly reflected by Hg sampled in blood and urine. From the National Health
      and Nutrition Examination Survey (NHANES, 2003-2008), 3769 adults aged 20 years
      and above were selected for analysis. Hepatic function was inferred from the
      three standard serum liver-related enzyme activities, aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT).
      Multivariate regression models were used to examine the associations of interest.
      Although urinary Hg was significantly correlated with serum Hg, the blood-urinary
      Hg relationship was influenced by liver function, which is also a function of
      demographic and lifestyle factors (e.g., gender). Although the results were only
      marginally significant for examined enzymes (p=0.06-0.08), urinary Hg tended to
      be lower among subjects with elevated liver enzymes, as compared to those with
      normal enzyme measurements. Conversely, MeHg generally represents a higher
      fraction of the total circulating Hg among those with elevated liver enzyme
      levels, especially among participants with elevations in all three enzymes
      (p=0.01). In conclusion, this population-based study identified an association
      between liver function, serum Hg and urinary Hg. Urinalysis may not be the
      optimal approach to monitor Hg elimination toxicokinetics or Hg exposure, since
      the majority of Hg excretion is fecal and the fidelity of urinary excretion may
      depend on healthy liver function. Future prospective studies are warranted to
      expand these findings.

PMID- 24908643
TI  - [Audit of the bedside monitor alarms in a critical care unit].
AB  - AIMS: Quantifying and evaluating the response to the bedside monitor alarms (BMA)
      by nurses in intensive care unit (ICU). METODOLOGY: Prospective observational
      study (October 2011-January 2012). Randomized blind audit on alarm management.
      Alarm programming and alarm limits were related to experience in ICU. We
      evaluated the response to BMA with the variables: alarm type (relevant/not
      relevant/alert) and response type. Descriptive analysis of variables for
      multivariate ANOVA and Chi-square test with SPSS 17.0. RESULTS: 434 audits were
      analyzed. The programming was: Blood pressure (BP) 88.25%, heart rate (HR) 98.62%
      O(2) saturation (SO) 96.79%, respiratory rate (FR) 65.75%. The alarms originated
      were BP 49.73%, 10.75% HR, 39.25% SO, 3.27% FS. The nurse responded to 93.3% of
      them and 50% were treated before 10 sec. 56.16% of the alarms were not relevant,
      25.12% relevant and 18.72% alerting. 41.8% were due to handling. CONCLUSION: The
      alarms are programmed/attended by the nurse and there is uniformity in
      programming/selection limits. 25% of BMA carried therapeutic attitude.

PMID- 24908644
TI  - A new approach to assessing the water footprint of wine: an Italian case study.
AB  - Agriculture is the largest freshwater consumer, accounting for 70% of the world's
      water withdrawal. Water footprints (WFs) are being increasingly used to indicate
      the impacts of water use by production systems. A new methodology to assess WF of
      wine was developed in the framework of the V.I.V.A. project (Valutazione Impatto
      Viticoltura sull'Ambiente), launched by the Italian Ministry for the Environment
      in 2011 to improve the Italian wine sector's sustainability. The new methodology
      has been developed that enables different vines from the same winery to be
      compared. This was achieved by calculating the gray water footprint, following
      Tier III approach proposed by Hoekstra et al. (2011). The impact of water use
      during the life cycle of grape-wine production was assessed for six different
      wines from the same winery in Sicily, Italy using both the newly developed
      methodology (V.I.V.A.) and the classical methodology proposed by the Water
      Footprint Network (WFN). In all cases green water was the largest contributor to
      WF, but the new methodology also detected differences between vines of the same
      winery. Furthermore, V.I.V.A. methodology assesses water body contamination by
      pesticides application whereas the WFN methodology considers just fertilization.
      This fact ended highlights the highest WF of vineyard 4 calculated by V.I.V.A. if
      compared with the WF calculated with WFN methodology. Comparing the WF of wine
      produced with grapes from the six different wines, the factors most greatly
      influencing the results obtained in this study were: distance from the water
      body, fertilization rate, amount and eco-toxicological behavior of the active
      ingredients used. 

PMID- 24908645
TI  - Human and bovine viruses in the Milwaukee River watershed: hydrologically
      relevant representation and relations with environmental variables.
AB  - To examine the occurrence, hydrologic variability, and seasonal variability of
      human and bovine viruses in surface water, three stream locations were monitored
      in the Milwaukee River watershed in Wisconsin, USA, from February 2007 through
      June 2008. Monitoring sites included an urban subwatershed, a rural subwatershed,
      and the Milwaukee River at the mouth. To collect samples that characterize
      variability throughout changing hydrologic periods, a process control system was
      developed for unattended, large-volume (56-2800 L) filtration over extended
      durations. This system provided flow-weighted mean concentrations during runoff
      and extended (24-h) low-flow periods. Human viruses and bovine viruses were
      detected by real-time qPCR in 49% and 41% of samples (n=63), respectively. All
      human viruses analyzed were detected at least once including adenovirus (40% of
      samples), GI norovirus (10%), enterovirus (8%), rotavirus (6%), GII norovirus
      (1.6%) and hepatitis A virus (1.6%). Three of seven bovine viruses analyzed were
      detected including bovine polyomavirus (32%), bovine rotavirus (19%), and bovine
      viral diarrhea virus type 1 (5%). Human viruses were present in 63% of runoff
      samples resulting from precipitation and snowmelt, and 20% of low-flow samples.
      Maximum human virus concentrations exceeded 300 genomic copies/L. Bovine viruses
      were present in 46% of runoff samples resulting from precipitation and snowmelt
      and 14% of low-flow samples. The maximum bovine virus concentration was 11
      genomic copies/L. Statistical modeling indicated that stream flow, precipitation,
      and season explained the variability of human viruses in the watershed, and
      hydrologic condition (runoff event or low-flow) and season explained the
      variability of the sum of human and bovine viruses; however, no model was
      identified that could explain the variability of bovine viruses alone.
      Understanding the factors that affect virus fate and transport in rivers will aid
      watershed management for minimizing human exposure and disease transmission.

PMID- 24908646
TI  - Life cycle assessment of nutrient removal technologies for the treatment of
      anaerobic digestion supernatant and its integration in a wastewater treatment
      plant.
AB  - The supernatant resulting from the anaerobic digestion of sludge generated by
      wastewater treatment plants (WWTP) is an attractive flow for technologies such as
      partial nitritation-anammox (CANON), nitrite shortcut (NSC) and struvite
      crystallization processes (SCP). The high concentration of N and P and its low
      flow rate facilitate the removal of nutrients under more favorable conditions
      than in the main water line. Despite their operational and economic benefits, the
      environmental burdens of these technologies also need to be assessed to prove
      their feasibility under a more holistic perspective. The potential environmental
      implications of these technologies were assessed using life cycle assessment,
      first at pilot plant scale, later integrating them in a modeled full WWTP. Pilot
      plant results reported a much lower environmental impact for N removal
      technologies than SCP. Full-scale modeling, however, highlighted that the
      differences between technologies were not relevant once they are integrated in a
      WWTP. The impacts associated with the WWTP are slightly reduced in all categories
      except for eutrophication, where a substantial reduction was achieved using NSC,
      SCP, and especially when CANON and SCP were combined. This study emphasizes the
      need for assessing wastewater treatment technologies as part of a WWTP rather
      than as individual processes and the utility of modeling tools for doing so. 

PMID- 24908647
TI  - Management of irrigation frequency and nitrogen fertilization to mitigate GHG and
      NO emissions from drip-fertigated crops.
AB  - Drip irrigation combined with split application of fertilizer nitrogen (N)
      dissolved in the irrigation water (i.e. drip fertigation) is commonly considered
      best management practice for water and nutrient efficiency. As a consequence, its
      use is becoming widespread. Some of the main factors (water-filled pore space,
      NH4(+) and NO3(-)) regulating the emissions of greenhouse gases (i.e. N2O, CO2
      and CH4) and NO from agroecosystems can easily be manipulated by drip fertigation
      without yield penalties. In this study, we tested management options to reduce
      these emissions in a field experiment with a melon (Cucumis melo L.) crop.
      Treatments included drip irrigation frequency (weekly/daily) and type of N
      fertilizer (urea/calcium nitrate) applied by fertigation. Crop yield,
      environmental parameters, soil mineral N concentrations and fluxes of N2O, NO,
      CH4 and CO2 were measured during 85 days. Fertigation with urea instead of
      calcium nitrate increased N2O and NO emissions by a factor of 2.4 and 2.9,
      respectively (P<0.005). Daily irrigation reduced NO emissions by 42% (P<0.005)
      but increased CO2 emissions by 21% (P<0.05) compared with weekly irrigation. We
      found no relation between irrigation frequency and N2O emissions. Based on yield
      scaled Global Warming Potential as well as NO cumulative emissions, we conclude
      that weekly fertigation with a NO3(-)-based fertilizer is the best option to
      combine agronomic productivity with environmental sustainability. Our study shows
      that adequate management of drip fertigation, while contributing to the
      attainment of water and food security, may provide an opportunity for climate
      change mitigation.

PMID- 24908648
TI  - Occurrence and ecological potential of pharmaceuticals and personal care products
      in groundwater and reservoirs in the vicinity of municipal landfills in China.
AB  - Pharmaceutical and personal care products (PPCPs), including antibiotics, azole
      anti-fungals, non-steroid anti-inflammatory drugs, lipid regulators, parabens,
      antiseptics, and bisphenol A, were investigated in groundwater and reservoirs in
      the vicinity of two municipal landfills in the metropolis of Guangzhou, South
      China. Dehydroerythromycin, sulfamethoxazole, fluconazole, salicylic acid,
      methylparaben, triclosan, and bisphenol A were the mostly frequently detected
      PPCPs in the groundwater at low ng L(-1) levels. In the reservoirs, the PPCPs
      were widely detected at higher frequencies and concentrations, especially
      sulfamethoxazole, propiconazole, and ibuprofen, with maximal concentrations above
      1 MUg L(-1). The PPCPs in the groundwater did not show significant seasonal
      differences or spatial trends. However, in the reservoirs, higher PPCP
      concentrations were observed in spring than in other seasons. The anti-bacterials
      in the groundwater posed medium risks to algae. In the reservoirs, the
      sulfonamides and macrolides posed low to high risks, while ibuprofen, salicylic
      acid, and clofibric acid presented low to medium risks to aquatic organisms.
      Overall, the results showed that the PPCP contaminants and subsequent ecological
      risks in the groundwater and surface water in the vicinity of the landfills may
      be of serious concern. More research is needed to better correlate the landfill
      leachates and PPCP contamination in the nearby aquatic environments.

PMID- 24908649
TI  - Sequential discriminant classification of environments with different levels of
      exposure to tobacco smoke.
AB  - The use of biomarkers permits the detection of smoking having taken place in an
      environment. However, no single biomarker is able to differentiate clearly
      between different types of environments. Multivariate classification models have
      helped us to differentiate between outdoors, non-smoking indoors, well ventilated
      smoking indoors, and smoking environments without good air exchange. We found
      that the variables that enabled us to classify environments most accurately were
      indoor temperature, 2,5-dimethylfuran and ethyltoluene. A successful prediction
      rate of 86.5% was obtained by applying both direct fitting and cross validation
      discriminant (leave-one-out) analyses. Our results show that although a good air
      exchange ratio decreases the levels of volatile organic compounds in indoor air
      due to tobacco smoke, significant contamination still remains. 

PMID- 24908650
TI  - The adoption of sustainable remediation behaviour in the US and UK: a cross
      country comparison and determinant analysis.
AB  - The sustainable remediation concept, aimed at maximizing the net environmental,
      social, and economic benefits in contaminated site remediation, is being
      increasingly recognized by industry, governments, and academia. However, there is
      limited understanding of actual sustainable behaviour being adopted and the
      determinants of such sustainable behaviour. The present study identified 27
      sustainable practices in remediation. An online questionnaire survey was used to
      rank and compare them in the US (n=112) and the UK (n=54). The study also rated
      ten promoting factors, nine barriers, and 17 types of stakeholders' influences.
      Subsequently, factor analysis and general linear models were used to determine
      the effects of internal characteristics (i.e. country, organizational
      characteristics, professional role, personal experience and belief) and external
      forces (i.e. promoting factors, barriers, and stakeholder influences). It was
      found that US and UK practitioners adopted many sustainable practices to similar
      extents. Both US and UK practitioners perceived the most effectively adopted
      sustainable practices to be reducing the risk to site workers, protecting
      groundwater and surface water, and reducing the risk to the local community.
      Comparing the two countries, we found that the US adopted innovative in-situ
      remediation more effectively; while the UK adopted reuse, recycling, and
      minimizing material usage more effectively. As for the overall determinants of
      sustainable remediation, the country of origin was found not to be a significant
      determinant. Instead, organizational policy was found to be the most important
      internal characteristic. It had a significant positive effect on reducing distant
      environmental impact, sustainable resource usage, and reducing remediation cost
      and time (p<0.01). Customer competitive pressure was found to be the most
      extensively significant external force. In comparison, perceived stakeholder
      influence, especially that of primary stakeholders (site owner, regulator, and
      primary consultant), did not appear to have as extensive a correlation with the
      adoption of sustainability as one would expect. 

PMID- 24908651
TI  - Long-term exposure to traffic-related air pollution and cardiovascular health in
      a Greek cohort study.
AB  - Our objective is to evaluate the association of exposure to traffic-related air
      pollution with the incidence of fatal and non-fatal ischemic heart disease (IHD),
      stroke and total cardiovascular disease (CVD) events in a Greek cohort. We used
      data from the European Prospective Investigation on Nutrition and Cancer (EPIC)
      for 2752 subjects followed from 1997 to 2011, whose residence was in 10
      municipalities of the Greater Athens area. Air pollution exposure estimation was
      based on a spatio-temporal land use regression model linking geo-coded
      residential addresses to long-term average NO2 and PM10 concentrations. We
      conducted Cox proportional hazards regression analysis, adjusting for potential
      confounders. Hazard ratios (HR) above 1 (not all statistically significant) were
      associated with higher PM10 exposure for all outcomes. Weaker associations were
      found with NO2 exposure. Specifically, the estimated HR for a CVD event
      associated with 10 MUg/m(3) increase in long-term exposure to PM10 was 1.50 (1.05
      2.16, p-value: 0.027). The relationship was more evident for subjects <=50 years
      old at recruitment. Associations of PM10 and NO2 exposure with IHD events were
      found only among women with HRs respectively of 2.24 (0.89-5.64, p-value: 0.086)
      and 1.54 (1.01-2.37, p-value: 0.046) associated with 10 MUg/m(3) increase in the
      corresponding pollutant. In conclusion, the present study suggests that long-term
      exposure to traffic-related air pollution has an impact on CVD and IHD morbidity,
      particularly among women and younger subjects.

PMID- 24908652
TI  - Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic
      agents.
AB  - The antiestrogenic activity of three natural salpichrolides A, G and B (1, 3 and
      4) and of five synthetic analogs containing an aromatic D ring and a simplified
      side chain (5-9), was evaluated on MCF-7 cells. The 2,3-ene-1-keto steroids 8 and
      9 were obtained from 3beta-acetoxy-17(13->18)-abeo-5alphaH-pregna-13,15,17-trien
      20-one, the key step for these syntheses being a Wharton carbonyl rearrangement
      of a 1,2-epoxy-3-keto steroid to the allylic alcohol using hydrazine hydrate. The
      antiestrogenic activity was evaluated by performing dose-response experiments in
      ER(+) MCF-7 breast cancer cells. Dose-dependent proliferation was quantified via
      [(3)H]-thymidine incorporation after 3 days treatment. Salpichrolides A, G and B
      and analogs 5, 8 and 9 were active as antiestrogens with compound 9 being the
      most active of the synthetic analogs. Compounds 5 and 9 were also evaluated
      against the ER(-) cell line MDA-MB-231 and shown to be inactive.

PMID- 24908653
TI  - Guanidine-based alpha2-adrenoceptor ligands: Towards selective antagonist
      activity.
AB  - Depression has been linked to a selective increase in the high affinity
      conformation of the alpha2-adrenergic autoreceptors (alpha2-ARs) in the human
      brain as well as to an overexpression of alpha2-ARs in the hippocampus and
      cerebral cortex. Thus, the development of novel alpha2-AR antagonists represents
      an attractive source of new antidepressants. This paper describes the design,
      synthesis and pharmacological evaluation of 30 new guanidinium and 2
      iminoimidazolidinium as potential alpha2-AR antagonists. In order to design this
      new series of alpha2-AR antagonists, a pharmacophore model was developed using
      the GALAHAD software. This study suggested that increased substitution in the
      space surrounding the cationic guanidine moiety might lead selectively to
      antagonist activity. Following the preparation of compounds incorporating this
      feature and competitive radioligand binding, [(35)S]GTPgammaS functional assays
      revealed that this structural modification affords exclusively alpha2-AR
      antagonists, in contrast with the analogous unsubstituted compounds in which a
      mixture of antagonist/agonist activities was previously observed. 

PMID- 24908654
TI  - Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating
      ABCA1 and SR-BI within RCT.
AB  - ABCA1 and scavenger receptor class B type I (SR-BI)/CD36 and lysosomal integral
      membrane protein II analogous 1 (CLA-1) are the key transporter and receptor in
      reverse cholesterol transport (RCT). Increasing the expression level of ABCA1 and
      SR-BI/CLA-1 is antiatherogenic. The aim of the study was to find novel
      antiatherosclerotic agents upregulating expression of ABCA1 and SR-BI/CLA-1 from
      natural compounds. Using the ABCA1p-LUC and CLA-1p-LUC HepG2 cell lines, we found
      that rutaecarpine (RUT) triggered promoters of ABCA1 and CLA-1 genes. RUT
      increased ABCA1 and SR-BI/CLA-1 expression in vitro related to liver X receptor
      alpha and liver X receptor beta. RUT induced cholesterol efflux in RAW264.7
      cells. ApoE-deficient (ApoE(-/-)) mice treated with RUT for 8 weeks showed
      ~68.43, 70.23, and 85.56% less en face lesions for RUT (L), RUT (M), and RUT (H)
      groups, respectively, compared with the model group. Mouse macrophage-specific
      antibody and filipin staining indicated that RUT attenuated macrophages and
      cholesterol accumulations in atherosclerotic lesions, respectively. Additionally,
      ABCA1 and SR-BI expression was highly induced by RUT in livers of ApoE(-/-) mice.
      Meanwhile, RUT treatment significantly increased the fecal (3)H-cholesterol
      excretion, which demonstrated that RUT could promote RCT in vivo. RUT was
      identified to be a candidate that protected ApoE(-/-) mice from developing
      atherosclerosis through preferentially promoting activities of ABCA1 and SR-BI
      within RCT. 

PMID- 24908655
TI  - Prospective evaluation of local control and late effects of conformal radiation
      therapy in children, adolescents, and young adults with high-grade glioma.
AB  - BACKGROUND: A phase II trial of conformal radiotherapy (CRT) for pediatric high
      grade glioma (HGG) was performed to evaluate disease control and late effects.
      METHODS: Between July 1997 and January 2003, 34 pediatric patients (median age,
      13.2 +/- 6.7 years) with HGG were enrolled on an International Commission on
      Radiation Units and Measurements Report 50-compliant prospective trial using CRT
      with a 2 cm clinical target volume margin. Baseline and serial evaluations were
      performed to assess functional outcomes. RESULTS: Median follow-up for the entire
      group was 18 months (range, 2-134 months). Twenty (58.8%) patients developed
      local progression, and 6 (17.6%) patients developed distant progression.
      Progression-free and overall survival at 10 years were 18.8% +/- 6.9% and 16.8%
      +/- 6.5%, respectively. At baseline, 40% of patients evaluated for intelligence
      quotient (IQ) scored below 85. Measures of cognitive function obtained during the
      first 12 months fit a mixed model with a quadratic function. The relationship
      between IQ and time was -1.1883 points/month for the linear term and 0.07728
      points/month for the quadratic term (P = .0454). IQ decreased between baseline
      and 6 months and then increased slightly through 12 months. The opposite was
      found for (all P values of the quadratic term) activities of daily living (P =
      .0155), socialization (P = .0049), and the composite score (P = .0257) of
      adaptive behavior. CONCLUSION: CRT using a 2 cm clinical target volume margin in
      pediatric HGG demonstrated tumor control comparable to conventional radiation
      therapy. Disrupted cognitive and adaptive behavioral functioning were present at
      baseline and throughout the course of disease.

PMID- 24908663
TI  - Warfarin increases stroke risk in atrial fibrillation.

PMID- 24908656
TI  - A phase I trial of veliparib (ABT-888) and temozolomide in children with
      recurrent CNS tumors: a pediatric brain tumor consortium report.
AB  - BACKGROUND: A phase I trial of veliparib (ABT-888), an oral poly(ADP-ribose)
      polymerase (PARP) inhibitor, and temozolomide (TMZ) was conducted in children
      with recurrent brain tumors to (i) estimate the maximum tolerated doses (MTDs) or
      recommended phase II doses (RP2Ds) of veliparib and TMZ; (ii) describe the
      toxicities of this regimen; and (iii) evaluate the plasma pharmacokinetic
      parameters and extent of PARP inhibition in peripheral blood mononuclear cells
      (PBMCs) following veliparib. METHODS: TMZ was given once daily and veliparib
      twice daily for 5 days every 28 days. Veliparib concentrations and poly(ADP
      ribose) (PAR) levels in PBMCs were measured on days 1 and 4. Analysis of
      pharmacokinetic and PBMC PAR levels were performed twice during study conduct to
      rationally guide dose modifications and to determine biologically optimal
      MTD/RP2D. RESULTS: Twenty-nine evaluable patients were enrolled. Myelosuppression
      (grade 4 neutropenia and thrombocytopenia) were dose limiting. The RP2Ds are
      veliparib 25 mg/m(2) b.i.d. and TMZ 135 mg/m(2)/d. Only 2 out of 12 patients
      treated at RP2Ds experienced dose-limiting toxicities. Although no objective
      response was observed, 4 patients had stable disease >6 months in duration,
      including 1 with glioblastoma multiforme and 1 with ependymoma. At the RP2D of
      veliparib, pediatric pharmacokinetic parameters were similar to those in adults.
      CONCLUSIONS: Veliparib and TMZ at the RP2D were well tolerated in children with
      recurrent brain tumors. A phase I/II trial to evaluate the tolerability and
      efficacy of veliparib, TMZ, and radiation in children with newly diagnosed
      brainstem gliomas is in progress.

PMID- 24908664
TI  - Late gadolinium enhancement assessed by cardiac magnetic resonance imaging in
      heart transplant recipients with different stages of cardiac allograft
      vasculopathy.
AB  - AIMS: Cardiac allograft vasculopathy (CAV), which limits long-term survival after
      heart transplantation (HTX), is usually evaluated by coronary angiography (CA).
      Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is a non
      invasive technique that can detect CAV-related myocardial infarctions. We aimed
      to investigate the presence of LGE infarct-typical patterns in a large sample of
      HTX recipients and to correlate these findings with the severity of CAV assessed
      by CA. METHODS AND RESULTS: LGE-CMR was performed in 132 HTX patients on a 1.5-T
      MRI scanner (Philips, Best, the Netherlands). Infarct-typical LGE areas were
      identified as bright lesions with subendocardial involvement. Infarct-atypical
      LGE was classified as follows: (i) right ventricle (RV) insertion, (ii)
      intramural, (iii) epicardial, and (iv) diffuse. CA was performed for the
      assessment of CAV (CAV0 = no lesion, CAV1 = mild lesions, CAV2 = moderate
      lesions, CAV3 = severe lesions, or mild/moderate lesions with allograft
      dysfunction). Infarct-typical LGE patterns were detected in 29 (22%) patients
      distributed in all groups and they were already present in nearly every fifth
      CAV0 patient, increasing significantly among CAV groups (CAV0 = 19%, CAV1 = 10%,
      CAV2 = 36%, and CAV3 = 71%; P < 0.01). CONCLUSION: LGE-CMR was useful to identify
      myocardial scar possibly related to early CAV in a significant proportion of HTX
      recipients, otherwise classified as low-risk patients based on CA. Therefore, LGE
      CMR could be helpful to intensify CAV monitoring, medical therapy, and clinical
      risk stratification.

PMID- 24908665
TI  - Inhibition of protein translation by the DISC1-Boymaw fusion gene from a Scottish
      family with major psychiatric disorders.
AB  - The t(1; 11) translocation appears to be the causal genetic lesion with 70%
      penetrance for schizophrenia, major depression and other psychiatric disorders in
      a Scottish family. Molecular studies identified the disruption of the disrupted
      in-schizophrenia 1 (DISC1) gene by chromosome translocation at chromosome 1q42.
      Our previous studies, however, revealed that the translocation also disrupted
      another gene, Boymaw (also termed DISC1FP1), on chromosome 11. After
      translocation, two fusion genes [the DISC1-Boymaw (DB7) and the Boymaw-DISC1
      (BD13)] are generated between the DISC1 and Boymaw genes. In the present study,
      we report that expression of the DB7 fusion gene inhibits both intracellular NADH
      oxidoreductase activities and protein translation. We generated humanized DISC1
      Boymaw mice with gene targeting to examine the in vivo functions of the fusion
      genes. Consistent with the in vitro studies on the DB7 fusion gene, protein
      translation activity is decreased in the hippocampus and in cultured primary
      neurons from the brains of the humanized mice. Expression of Gad67, Nmdar1 and
      Psd95 proteins are also reduced. The humanized mice display prolonged and
      increased responses to the NMDA receptor antagonist, ketamine, on various mouse
      genetic backgrounds. Abnormal information processing of acoustic startle and
      depressive-like behaviors are also observed. In addition, the humanized mice
      display abnormal erythropoiesis, which was reported to associate with depression
      in humans. Expression of the DB7 fusion gene may reduce protein translation to
      impair brain functions and thereby contribute to the pathogenesis of major
      psychiatric disorders. 

PMID- 24908666
TI  - Latent TGF-beta binding protein-2 is essential for the development of ciliary
      zonule microfibrils.
AB  - Latent TGF-beta-binding protein-2 (LTBP-2) is an extracellular matrix protein
      associated with microfibrils. Homozygous mutations in LTBP2 have been found in
      humans with genetic eye diseases such as congenital glaucoma and
      microspherophakia, indicating a critical role of the protein in eye development,
      although the function of LTBP-2 in vivo has not been well understood. In this
      study, we explore the in vivo function of LTBP-2 by generating Ltbp2(-/-) mice.
      Ltbp2(-/-) mice survived to adulthood but developed lens luxation caused by
      compromised ciliary zonule formation without a typical phenotype related to
      glaucoma, suggesting that LTBP-2 deficiency primarily causes lens dislocation but
      not glaucoma. The suppression of LTBP2 expression in cultured human ciliary
      epithelial cells by siRNA disrupted the formation of the microfibril meshwork by
      the cells. Supplementation of recombinant LTBP-2 in culture medium not only
      rescued the microfibril meshwork formation in LTBP2-suppressed ciliary epithelial
      cells but also restored unfragmented and bundled ciliary zonules in Ltbp2(-/-)
      mouse eyes under organ culture. Although several reported human mutant LTBP-2
      proteins retain normal domain structure and keep the fibrillin-1-binding site
      intact, none of these mutant proteins were secreted from their producing cells,
      suggesting secretion arrest occurred to the LTBP-2 mutants owing to
      conformational alteration. The findings of this study suggest that LTBP-2 is an
      essential component for the formation of microfibril bundles in ciliary zonules. 

PMID- 24908667
TI  - Bent bone dysplasia syndrome reveals nucleolar activity for FGFR2 in ribosomal
      DNA transcription.
AB  - Fibroblast growth factor receptor 2 (FGFR2) promotes osteoprogenitor
      proliferation and differentiation during bone development, yet how the receptor
      elicits these distinct cellular responses remains unclear. Analysis of the FGFR2
      skeletal disorder bent bone dysplasia syndrome (BBDS) demonstrates that FGFR2, in
      addition to its canonical signaling activities at the plasma membrane, regulates
      bone formation from within the nucleolus. Previously, we showed that the unique
      FGFR2 mutations that cause BBDS reduce receptor levels at the plasma membrane and
      diminish responsiveness to extracellular FGF2. In this study, we find that these
      mutations, despite reducing canonical signaling, enhance nucleolar occupancy of
      FGFR2 at the ribosomal DNA (rDNA) promoter. Nucleolar FGFR2 activates rDNA
      transcription via interactions with FGF2 and UBF1 by de-repressing RUNX2. An
      increase in the nucleolar activity of FGFR2 in BBDS elevates levels of ribosomal
      RNA in the developing bone, consequently promoting osteoprogenitor cell
      proliferation and decreasing differentiation. Identifying FGFR2 as a
      transcriptional regulator of rDNA in bone unexpectedly reveals a nucleolar route
      for FGF signaling that allows for independent regulation of osteoprogenitor cell
      proliferation and differentiation. 

PMID- 24908668
TI  - Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary
      spastic paraplegia SPG3A.
AB  - Hereditary spastic paraplegias are a large, diverse group of neurological
      disorders (SPG1-71) with the unifying feature of prominent lower extremity
      spasticity, owing to a length-dependent axonopathy of corticospinal motor
      neurons. The most common early-onset form of pure, autosomal dominant hereditary
      spastic paraplegia is caused by mutation in the ATL1 gene encoding the atlastin-1
      GTPase, which mediates homotypic fusion of ER tubules to form the polygonal ER
      network. We have identified a p.Pro342Ser mutation in a young girl with pure
      SPG3A. This residue is in a critical hinge region of atlastin-1 between its
      GTPase and assembly domains, and it is conserved in all known eukaryotic atlastin
      orthologs. We produced induced pluripotent stem cells from skin fibroblasts and
      differentiated these into forebrain neurons to generate a human neuronal model
      for SPG3A. Axons of these SPG3A neurons showed impaired growth, recapitulating
      axonal defects in atlastin-1-depleted rat cortical neurons and impaired root hair
      growth in loss-of-function mutants of the ATL1 ortholog rhd3 in the plant
      Arabidopsis. Both the microtubule cytoskeleton and tubular ER are important for
      mitochondrial distribution and function within cells, and SPG3A neurons showed
      alterations in mitochondrial motility. Even so, it is not clear whether this
      change is involved in disease pathogenesis. The SPG3A axon growth defects could
      be rescued with microtubule-binding agents, emphasizing the importance of tubular
      ER interactions with the microtubule cytoskeleton in hereditary spastic
      paraplegia pathogenesis. The prominent alterations in axon growth in SPG3A
      neurons may represent a particularly attractive target for suppression in screens
      for novel pharmacologic agents. 

PMID- 24908669
TI  - Hypermethylation of the CpG-island near the C9orf72 G4C2-repeat expansion in FTLD
      patients.
AB  - The G4C2-repeat expansion in C9orf72 is a common cause of frontotemporal lobar
      degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72
      transcription is reduced in expansion carriers implicating haploinsufficiency as
      one of the disease mechanisms. Indeed, our recent ALS study revealed that the
      expansion was associated with hypermethylation of the CpG-island (5'of the
      repeat) in DNA samples obtained from different tissues (blood, brain and spinal
      cord). However, the link between FTLD and methylation of the CpG-island is
      unknown. Hence, we investigated the methylation profile of the same CpG-island by
      bisulfite sequencing of DNA obtained from blood of 34 FTLD expansion carriers,
      166 FTLD non-carriers and 103 controls. Methylation level was significantly
      higher in FTLD expansion carriers than non-carriers (P = 7.8E-13). Our results
      were confirmed by two methods (HhaI-assay and sequencing of cloned bisulfite PCR
      products). Hypermethylation occurred only in carriers of an allele with >50
      repeats, and was not detected in non-carriers or individuals with an intermediate
      allele (22-43 repeats). As expected, the position/number of methylated CpGs was
      concordant between the sense and anti-sense DNA strand, suggesting that it is a
      stable epigenetic modification. Analysis of the combined ALS and FTLD datasets
      (82 expansion carriers) revealed that the degree of methylation of the entire CpG
      island or contribution of specific CpGs (n = 26) is similar in both syndromes,
      with a trend towards a higher proportion of ALS patients with a high methylation
      level (P = 0.09). In conclusion, we demonstrated that hypermethylation of the CpG
      island 5'of the G4C2-repeat is expansion-specific, but not syndrome-specific (ALS
      versus FTLD).

PMID- 24908671
TI  - Birthweight percentiles by gestational age for births following assisted
      reproductive technology in Australia and New Zealand, 2002-2010.
AB  - STUDY QUESTION: What is the standard of birthweight for gestational age for
      babies following assisted reproductive technology (ART) treatment? SUMMARY
      ANSWER: Birthweight for gestational age percentile charts were developed for
      singleton births following ART treatment using population-based data. WHAT IS
      KNOWN ALREADY: Small for gestational age (SGA) and large for gestational age
      (LGA) births are at increased risks of perinatal morbidity and mortality. A
      birthweight percentile chart allows the detection of neonates at high risk, and
      can help inform the need for special care if required. STUDY DESIGN, SIZE,
      DURATION: This population study used data from the Australian and New Zealand
      Assisted Reproduction Database (ANZARD) for 72 694 live born singletons following
      ART treatment between January 2002 and December 2010 in Australia and New
      Zealand. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 69 315 births (35
      580 males and 33 735 females) following ART treatment were analysed for the
      birthweight percentile. Exact percentiles of birthweight in grams were calculated
      for each gestational week between Week 25 and 42 for fresh and thaw cycles by
      infant sex. Univariate analysis was used to determine the exact birthweight
      percentile values. Student t-test was used to examine the mean birthweight
      difference between male and female infants, between single embryo transfer (SET)
      and double embryo transfer (DET) and between fresh and thaw cycles. MAIN RESULTS
      AND THE ROLE OF CHANCE: Preterm births (birth before 37 completed weeks of
      gestation) and low birthweight (<2500 g) were reported for 9.7 and 7.0% of live
      born singletons following ART treatment. The mean birthweight was 3280 g for live
      born singletons following fresh cycles (3338 g for male infants and 3217 for
      female infants) and 3413 g for live born singletons following thaw cycles (3475 g
      for male infants and 3349 for female infants). The proportion of SGA for male ART
      births following thaw cycles at 35-41 weeks gestation was significantly lower
      than for the Australian general population, ranging from 3.8% (95% confidence
      interval (CI): 1.3%, 6.2%) at 35 weeks gestation to 7.9% (95% CI: 6.3%, 9.5%) at
      41 weeks gestation. The proportion of LGA for male ART births following thaw
      cycles was significantly higher than for the Australian general population
      between 33 weeks (17.1%, 95% CI: 8.9%, 25.2%) and 41 weeks (14.4%, 95% CI: 12.3%,
      16.5%). A similar trend was shown for female infants following thaw cycles. The
      live born singletons following SET were, on average, 45 g heavier than live born
      singletons following DET (P< 0.001). Overall, SGA was reported for 8.9% (95% CI:
      8.6%, 9.1%) of live born singletons following SET and for 9.9% (95% CI: 9.5%,
      10.3%) of live born singletons following DET. LIMITATIONS, REASONS FOR CAUTION:
      Birthweight percentile charts do not represent fetal growth standards but only
      the weight of live born infants at birth. WIDER IMPLICATIONS OF THE FINDINGS: The
      comparison of birthweight percentile charts for ART births and general population
      births provide evidence that the proportion of SGA births following ART treatment
      was comparable to the general population for SET fresh cycles and significantly
      lower for thaw cycles. Both fresh and thaw cycles showed better outcomes for
      singleton births following SET compared with DET. Policies to promote single
      embryo transfer should be considered in order to minimize the adverse perinatal
      outcomes associated with ART treatment. STUDY FUNDING/COMPETING INTERESTS: No
      specific funding was obtained. The authors have no conflicts of interest to
      declare.

PMID- 24908672
TI  - The Bologna criteria for poor ovarian response: the good, the bad and the way
      forward.
AB  - The management of poor ovarian response (POR) remains one of the most significant
      challenges of in vitro fertilization. Numerous interventions have been proposed,
      yet few have been shown to be beneficial. The most important problem in
      evaluating the available evidence has been the lack of a standardized definition
      of POR. The Bologna criteria for POR have been recently introduced to provide a
      framework allowing future research in this field to be performed on a relatively
      homogenous population. However, it has been suggested that the population
      described by the Bologna criteria might not be sufficiently homogenous and for
      this reason stratified randomization should be used in relevant randomized
      controlled trials (RCTs). Stratified randomization, besides its advantages, also
      has important shortcomings and for this reason it should be used only when there
      is clear evidence mandating such a design. Currently, there is insufficient data
      to support such practice in RCTs performed on the population described by the
      Bologna criteria for POR. Until such evidence becomes available, the scientific
      community should aim at evaluating interventions for POR according to the Bologna
      criteria in RCTs of sufficient sample size, with proper allocation concealment
      and masking. 

PMID- 24908670
TI  - Folliculin (Flcn) inactivation leads to murine cardiac hypertrophy through mTORC1
      deregulation.
AB  - Cardiac hypertrophy, an adaptive process that responds to increased wall stress,
      is characterized by the enlargement of cardiomyocytes and structural remodeling.
      It is stimulated by various growth signals, of which the mTORC1 pathway is a well
      recognized source. Here, we show that loss of Flcn, a novel AMPK-mTOR interacting
      molecule, causes severe cardiac hypertrophy with deregulated energy homeostasis
      leading to dilated cardiomyopathy in mice. We found that mTORC1 activity was
      upregulated in Flcn-deficient hearts, and that rapamycin treatment significantly
      reduced heart mass and ameliorated cardiac dysfunction. Phospho-AMP-activated
      protein kinase (AMPK)-alpha (T172) was reduced in Flcn-deficient hearts and
      nonresponsive to various stimulations including metformin and AICAR (5-amino-1
      beta-D-ribofuranosyl-imidazole-4-carboxamide). ATP levels were elevated and
      mitochondrial function was increased in Flcn-deficient hearts, suggesting that
      excess energy resulting from up-regulated mitochondrial metabolism under Flcn
      deficiency might attenuate AMPK activation. Expression of Ppargc1a, a central
      molecule for mitochondrial metabolism, was increased in Flcn-deficient hearts and
      indeed, inactivation of Ppargc1a in Flcn-deficient hearts significantly reduced
      heart mass and prolonged survival. Ppargc1a inactivation restored phospho-AMPK
      alpha levels and suppressed mTORC1 activity in Flcn-deficient hearts, suggesting
      that up-regulated Ppargc1a confers increased mitochondrial metabolism and excess
      energy, leading to inactivation of AMPK and activation of mTORC1. Rapamycin
      treatment did not affect the heart size of Flcn/Ppargc1a doubly inactivated
      hearts, further supporting the idea that Ppargc1a is the critical element leading
      to deregulation of the AMPK-mTOR-axis and resulting in cardiac hypertrophy under
      Flcn deficiency. These data support an important role for Flcn in cardiac
      homeostasis in the murine model. 

PMID- 24908673
TI  - Expression patterns of DLK1 and INSL3 identify stages of Leydig cell
      differentiation during normal development and in testicular pathologies,
      including testicular cancer and Klinefelter syndrome.
AB  - STUDY QUESTION: What is the differentiation stage of human testicular
      interstitial cells, in particular Leydig cells (LC), within micronodules found in
      patients with infertility, testicular cancer and Klinefelter syndrome? SUMMARY
      ANSWER: The Leydig- and peritubular-cell populations in testes with dysgenesis
      contain an increased proportion of undifferentiated cells when compared with
      control samples, as demonstrated by increased delta-like homolog 1 (DLK1) and
      decreased insulin-like peptide 3 (INSL3) expression. WHAT IS KNOWN ALREADY:
      Normal LC function is essential for male development and reproduction. Signs of
      LC failure, including LC micronodules, are often observed in patients with
      reproductive disorders. STUDY DESIGN, SIZE, PARTICIPANTS: In this retrospective
      study, a panel of markers and factors linked to the differentiation of LCs was
      investigated in 33 fetal and prepubertal human specimens and in 58 adult testis
      samples from patients with testicular germ cell tumours, including precursor
      carcinoma in situ (CIS), infertility or Klinefelter syndrome.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression patterns of DLK1, INSL3,
      chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII),
      cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1) and smooth
      muscle actin (SMA) were investigated by immunohistochemistry and quantitative RT
      PCR. The percentage of positive LCs was estimated and correlated to total LC
      numbers and serum levels of reproductive hormones. MAIN RESULTS AND THE ROLE OF
      CHANCE: DLK1, INSL3 and COUP-TFII expression changed during normal development
      and was linked to different stages of LC differentiation: DLK1 was expressed in
      all fetal LCs, but only in spindle-shaped progenitor cells and in a small subset
      of polygonal LCs in the normal adult testis; INSL3 was expressed in a subset of
      fetal LCs, but in the majority of adult LCs; and COUP-TFII was expressed in
      peritubular and mesenchymal stroma cells at all ages, in fetal LCs early in
      gestation and in a subset of adult LCs. CYP11A1 was expressed in the majority of
      LCs regardless of age and pathology and was the best general LC marker examined
      here. SMA was weakly expressed in peritubular cells in the fetal and infantile
      testis, but strongly expressed in the adult testis. In pathological testes, the
      numbers of DLK1-positive interstitial cells were increased. The proportion of
      DLK1-positive LCs correlated with total LC numbers (R = 0.53; P < 0.001) and was
      higher in testis with enlargement of the peritubular layers (P < 0.01), which was
      also highly associated with DLK1 expression in the peritubular compartment (P <
      0.001). INSL3 expression was absent in some, but not all LC micronodules, and in
      the majority of LCs, it was mutually exclusive of DLK1. LIMITATIONS, REASONS FOR
      CAUTION: The number of samples was relatively small and no true normal adult
      controls were available. True stereology was not used for LC counting, instead
      LCs were counted in three fields of 0.5 um(2) surface for each sample. WIDER
      IMPLICATIONS OF THE FINDINGS: The population of LCs, especially those clustered
      in large nodules, are heterogeneous and comprise cells at different stages of
      differentiation. The study demonstrated that the differentiation and function of
      LCs, and possibly also peritubular cells, are impaired in adult men with
      testicular pathologies including testis cancer and Klinefelter syndrome. STUDY
      FUNDING/COMPETING INTERESTS: This work was funded by Rigshospitalet's research
      funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation.
      The authors have no conflicts of interest.

PMID- 24908674
TI  - Ovarian suspension for longer than 36 h is necessary for temporary ovarian
      suspension to fulfil its remit.

PMID- 24908675
TI  - Reply: ovarian suspension for longer than 36 h is necessary for temporary ovarian
      suspension to fulfil its remit.

PMID- 24908676
TI  - Networking the country to promote health and scientific discovery.

PMID- 24908678
TI  - A novel mucosal vaccine targeting Peyer's patch M cells induces protective
      antigen-specific IgA responses.
AB  - Mucosal vaccines can induce mucosal immunity, including antigen-specific
      secretory IgA production, to protect from invasion by pathogens and to neutralize
      toxins at mucosal surfaces. We established an effective antigen-delivering fusion
      protein, anti-GP2-SA, as a mucosal vaccine. The anti-GP2-SA consists of
      streptavidin (SA) fused to the antigen-binding fragment region from a mAb against
      glycoprotein 2 (GP2), an antigen-uptake receptor specifically expressed on M
      cells. Anti-GP2-SA targets antigen-sampling M cells in the follicle-associated
      epithelium covering Peyer's patches. Immunofluorescence showed that anti-GP2-SA
      specifically bound to M cells. Orally administered biotinylated ovalbumin peptide
      (bOVA) conjugated with anti-GP2-SA more efficiently induced OVA-specific fecal
      IgA secretion compared with bOVA alone or bOVA conjugated with SA. Furthermore,
      mice immunized by oral administration of the biotinylated Salmonella enterica
      serovar Typhimurium (S. Typhimurium) lysate conjugated with anti-GP2-SA were
      significantly better protected from subsequent infection by virulent S.
      Typhimurium than mice treated with the bacterial lysate alone or conjugated with
      SA. These results suggest that anti-GP2-SA-based M-cell-targeting vaccines are a
      novel strategy for inducing efficient mucosal immunity. 

PMID- 24908679
TI  - NF-kappaB RELA-deficient bone marrow macrophages fail to support bone formation
      and to maintain the hematopoietic niche after lethal irradiation and stem cell
      transplantation.
AB  - Bone remodeling and hematopoiesis are interrelated and bone marrow (BM)
      macrophages are considered to be important for both bone remodeling and
      maintenance of the hematopoietic niche. We found that NF-kappaB Rela-deficient
      chimeric mice, generated by transplanting Rela (-/-) fetal liver cells into
      lethally irradiated hosts, developed severe osteopenia, reduced lymphopoiesis and
      enhanced mobilization of hematopoietic stem and progenitor cells when BM cells
      were completely substituted by Rela-deficient cells. Rela (-/-) hematopoietic
      stem cells from fetal liver had normal hematopoietic ability, but those harvested
      from the BM of osteopenic Rela (-/-) chimeric mice had reduced repopulation
      ability, indicating impairment of the microenvironment for the hematopoietic
      niche. Osteopenia in Rela (-/-) chimeric mice was due to reduced bone formation,
      even though osteoblasts differentiated from host cells. This finding indicates
      impaired functional coupling between osteoblasts and hematopoietic stem cell
      derived cells. Rela-deficient BM macrophages exhibited an aberrant inflammatory
      phenotype, and transplantation with wild-type F4/80(+) BM macrophages recovered
      bone formation and ameliorated lymphopoiesis in Rela (-/-) chimeric mice.
      Therefore, RELA in F4/80(+) macrophages is important both for bone homeostasis
      and for maintaining the hematopoietic niche after lethal irradiation and
      hematopoietic stem cell transplantation. 

PMID- 24908680
TI  - Recovery and fine structure variability of RGII sub-domains in wine (Vitis
      vinifera Merlot).
AB  - BACKGROUND AND AIMS: Rhamnogalacturonan II (RGII) is a structurally complex
      pectic sub-domain composed of more than 12 different sugars and 20 different
      linkages distributed in five side chains along a homogalacturonan backbone.
      Although RGII has long been described as highly conserved over plant evolution,
      recent studies have revealed variations in the structure of the polysaccharide.
      This study examines the fine structure variability of RGII in wine, focusing on
      the side chains A and B obtained after sequential mild acid hydrolysis.
      Specifically, this study aims to differentiate intrinsic structural variations in
      these RGII side chains from structural variations due to acid hydrolysis.
      METHODS: RGII from wine (Vitis vinifera Merlot) was sequentially hydrolysed with
      trifluoroacetic acid (TFA) and the hydrolysis products were separated by anion
      exchange chromatography (AEC). AEC fractions or total hydrolysates were analysed
      by MALDI-TOF mass spectrometry. KEY RESULTS: The optimal conditions to recover
      non-degraded side chain B, side chain A and RGII backbone were 0.1 m TFA at 40 
      degrees C for 16 h, 0.48 m TFA at 40  degrees C for 16 h (or 0.1 m TFA at 60 
      degrees C for 8 h) and 0.1 m TFA at 60  degrees C for 16 h, respectively. Side
      chain B was particularly prone to acid degradation. Side chain A and the RGII
      GalA backbone were partly degraded by 0.1 m TFA at 80  degrees C for 1-4 h. AEC
      allowed separation of side chain B, methyl-esterified side chain A and non-methyl
      esterified side chain A. The structure of side chain A and the GalA backbone were
      highly variable. CONCLUSIONS: Several modifications to the RGII structure of wine
      were identified. The observed dearabinosylation and deacetylation were primarily
      the consequence of acidic treatment, while variation in methyl-esterification,
      methyl-ether linkages and oxidation reflect natural diversity. The physiological
      significance of this variability, however, remains to be determined.

PMID- 24908681
TI  - Molecular phylogeny and biogeography of the fern genus Pteris (Pteridaceae).
AB  - BACKGROUND AND AIMS: Pteris (Pteridaceae), comprising over 250 species, had been
      thought to be a monophyletic genus until the three monotypic genera Neurocallis,
      Ochropteris and Platyzoma were included. However, the relationships between the
      type species of the genus Pteris, P. longifolia, and other species are still
      unknown. Furthermore, several infrageneric morphological classifications have
      been proposed, but are debated. To date, no worldwide phylogenetic hypothesis has
      been proposed for the genus, and no comprehensive biogeographical history of
      Pteris, crucial to understanding its cosmopolitan distribution, has been
      presented. METHODS: A molecular phylogeny of Pteris is presented for 135 species,
      based on cpDNA rbcL and matK and using maximum parsimony, maximum likelihood and
      Bayesian inference approaches. The inferred phylogeny was used to assess the
      biogeographical history of Pteris and to reconstruct the evolution of one
      ecological and four morphological characters commonly used for infrageneric
      classifications. KEY RESULTS: The monophyly of Pteris remains uncertain,
      especially regarding the relationship of Pteris with Actiniopteris + Onychium and
      Platyzoma. Pteris comprises 11 clades supported by combinations of ecological and
      morphological character states, but none of the characters used in previous
      classifications were found to be exclusive synapomorphies. The results indicate
      that Pteris diversified around 47 million years ago, and when species colonized
      new geographical areas they generated new lineages, which are associated with
      morphological character transitions. CONCLUSIONS: This first phylogeny of Pteris
      on a global scale and including more than half of the diversity of the genus
      should contribute to a new, more reliable infrageneric classification of Pteris,
      based not only on a few morphological characters but also on ecological traits
      and geographical distribution. The inferred biogeographical history highlights
      long-distance dispersal as a major process shaping the worldwide distribution of
      the species. Colonization of different niches was followed by subsequent
      morphological diversification. Dispersal events followed by allopatric and
      parapatric speciation contribute to the species diversity of Pteris.

PMID- 24908684
TI  - General and plastic surgery devices: reclassification of ultraviolet lamps for
      tanning, henceforth to be known as sunlamp products and ultraviolet lamps
      intended for use in sunlamp products. Final order.
AB  - The Food and Drug Administration (FDA or the Agency) is reclassifying ultraviolet
      (UV) lamps intended to tan the skin from class I (general controls) exempt from
      premarket notification to class II (special controls) and subject to premarket
      notification, and renaming them sunlamp products and UV lamps intended for use in
      sunlamp products. FDA is designating special controls that are necessary to
      provide a reasonable assurance of safety and effectiveness of the device. FDA is
      reclassifying this device on its own initiative based on new information.

PMID- 24908685
TI  - Medical devices; general and plastic surgery devices; classification of the
      powered surgical instrument for improvement in the appearance of cellulite. Final
      order.
AB  - The Food and Drug Administration (FDA) is classifying the powered surgical
      instrument for improvement in the appearance of cellulite into class II (special
      controls). The Agency is classifying the device into class II (special controls)
      in order to provide a reasonable assurance of safety and effectiveness of the
      device.

PMID- 24908686
TI  - Final priority; National Institute on Disability and Rehabilitation Research-
      Rehabilitation Engineering Research Centers. Final priority.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a priority for the Disability and Rehabilitation Research Projects and
      Centers Program administered by the National Institute on Disability and
      Rehabilitation Research (NIDRR). Specifically, we announce a priority for a
      Rehabilitation Engineering Research Center (RERC) on Technologies to Enhance
      Independence in Daily Living for Adults with Cognitive Impairments. The Assistant
      Secretary may use this priority for competitions in fiscal year (FY) 2014 and
      later years. We take this action to focus research attention on an area of
      national need. We intend the priority to contribute to improved outcomes related
      to independence in daily activities in the home, community, or workplace setting
      for adults with cognitive impairments.

PMID- 24908682
TI  - Stromal reengineering to treat pancreas cancer.
AB  - Pancreatic ductal adenocarcinoma co-opts multiple cellular and extracellular
      mechanisms to create a complex cancer organ with an unusual proclivity for
      metastasis and resistance to therapy. Cell-autonomous events are essential for
      the initiation and maintenance of pancreatic ductal adenocarcinoma, but recent
      studies have implicated critical non-cell autonomous processes within the robust
      desmoplastic stroma that promote disease pathogenesis and resistance. Thus, non
      malignant cells and associated factors are culprits in tumor growth,
      immunosuppression and invasion. However, even this increasing awareness of non
      cell autonomous contributions to disease progression is tempered by the
      conflicting roles stromal elements can play. A greater understanding of stromal
      complexity and complicity has been aided in part by studies in highly faithful
      genetically engineered mouse models of pancreatic ductal adenocarcinoma. Insights
      gleaned from such studies are spurring the development of therapies designed to
      reengineer the pancreas cancer stroma and render it permissive to agents
      targeting cell-autonomous events or to reinstate immunosurveillance. Integrating
      conventional and immunological treatments in the context of stromal targeting may
      provide the key to a durable clinical impact on this formidable disease.

PMID- 24908687
TI  - Establishing a list of qualifying pathogens under the Food and Drug
      Administration Safety and Innovation Act. Final rule.
AB  - The Food and Drug Administration (FDA or Agency) is issuing a regulation to
      establish a list of "qualifying pathogens'' that have the potential to pose a
      serious threat to public health. This final rule implements a provision of the
      Generating Antibiotic Incentives Now (GAIN) title of the Food and Drug
      Administration Safety and Innovation Act (FDASIA). GAIN is intended to encourage
      development of new antibacterial and antifungal drugs for the treatment of
      serious or life-threatening infections, and provides incentives such as
      eligibility for designation as a fast-track product and an additional 5 years of
      exclusivity to be added to certain exclusivity periods. Based on analyses
      conducted both in the proposed rule and in response to comments to the proposed
      rule, FDA has determined that the following pathogens comprise the list of
      ''qualifying pathogens:'' Acinetobacter species, Aspergillus species,
      Burkholderia cepacia complex, Campylobacter species, Candida species, Clostridium
      difficile, Coccidioides species, Cryptococcus species, Enterobacteriaceae (e.g.,
      Klebsiella pneumoniae), Enterococcus species, Helicobacter pylori, Mycobacterium
      tuberculosis complex, Neisseria gonorrhoeae, N. meningitidis, Non-tuberculous
      mycobacteria species, Pseudomonas species, Staphylococcus aureus, Streptococcus
      agalactiae, S. pneumoniae, S. pyogenes, and Vibrio cholerae. The preamble to the
      proposed rule described the factors the Agency considered and the methodology
      used to develop the list of qualifying pathogens. As described in the preamble of
      this final rule, FDA applied those factors and that methodology to additional
      pathogens suggested via comments on the proposed rule.

PMID- 24908683
TI  - Genetic variation in prostaglandin synthesis and related pathways, NSAID use and
      colorectal cancer risk in the Colon Cancer Family Registry.
AB  - Although use of non-steroidal anti-inflammatory drugs (NSAIDs) generally
      decreases colorectal cancer (CRC) risk, inherited genetic variation in
      inflammatory pathways may alter their potential as preventive agents. We
      investigated whether variation in prostaglandin synthesis and related pathways
      influences CRC risk in the Colon Cancer Family Registry by examining associations
      between 192 single nucleotide polymorphisms (SNPs) and two variable nucleotide
      tandem repeats (VNTRs) within 17 candidate genes and CRC risk. We further
      assessed interactions between these polymorphisms and NSAID use on CRC risk.
      Using a case-unaffected-sibling-control design, this study included 1621 primary
      invasive CRC cases and 2592 sibling controls among Caucasian men and women aged
      18-90. After adjustment for multiple comparisons, two intronic SNPs were
      associated with rectal cancer risk: rs11571364 in ALOX12 [OR(het/hzv) = 1.87, 95%
      confidence interval (CI) = 1.19-2.95, P = 0.03] and rs45525634 in PTGER2
      (OR(het/hzv) = 0.49, 95% CI = 0.29-0.82, P = 0.03). Additionally, there was an
      interaction between NSAID use and the intronic SNP rs2920421 in ALOX12 on risk of
      CRC (P = 0.03); among those with heterozygous genotypes, risk was reduced for
      current NSAID users compared with never or former users (OR(het) = 0.60, 95% CI =
      0.45-0.80), though not among those with homozygous wild-type or variant
      genotypes. The results of this study suggest that genetic variation in ALOX12 and
      PTGER2 may affect the risk of rectal cancer. In addition, this study suggests
      plausible interactions between NSAID use and variants in ALOX12 on CRC risk.
      These results may aid in the development of genetically targeted cancer
      prevention strategies with NSAIDs.

PMID- 24908689
TI  - Pulmonary embolism:  assessment and imaging.

PMID- 24908690
TI  - Reply: To PMID 24024223.

PMID- 24908688
TI  - Is human ingenuity  changing the face of  ischaemic heart disease?

PMID- 24908691
TI  - [Q & A: Tuberculoma of the liver, an old and yet new disease that should not be
      ignored].

PMID- 24908692
TI  - Clubbing.

PMID- 24908693
TI  - Osteoarthritis.

PMID- 24908694
TI  - Reply: To PMID 24217094.

PMID- 24908695
TI  - Health experts consider pandemic risks of influenza viruses, coronaviruses.

PMID- 24908696
TI  - A practitioner, through and through AVMA President Fobian reflects on his time in
      office.

PMID- 24908697
TI  - Students plugged in at symposium. SAVMA gathering mixes learning, entertainment.

PMID- 24908698
TI  - Learning the ropes.

PMID- 24908699
TI  - Report highlights growing practices. Driving success are bonds between pets and
      owners, other relationships.

PMID- 24908701
TI  - Mentorship, internship models  evolving to meet needs.

PMID- 24908700
TI  - AAHA conference digs into secrets of success.

PMID- 24908702
TI  - Crumley takes helm of AAHA.

PMID- 24908703
TI  - Cat transmits TB to humans in UK.

PMID- 24908704
TI  - Novel pain assessment developed for horses.

PMID- 24908705
TI  - Companies to reduce antimicrobial availability.

PMID- 24908706
TI  - Biofilm-infected wounds.

PMID- 24908707
TI  - The authors respond.

PMID- 24908708
TI  - Antimicrobials and  antimicrobial resistance.

PMID- 24908709
TI  - Should fathers be present at childbirth?

PMID- 24908710
TI  - Want to be a general nurse?

PMID- 24908711
TI  - How evidence-based practice can provide the way forward for third stage care.

PMID- 24908712
TI  - The impact of smoking on baby death rate inequalities.

PMID- 24908714
TI  - Life's a beach (party).

PMID- 24908713
TI  - How to ... measure a baby's temperature.

PMID- 24908715
TI  - Who's in the mix?

PMID- 24908716
TI  - Lessons in respect.

PMID- 24908717
TI  - It's the person that counts.

PMID- 24908718
TI  - When silence isn't golden.

PMID- 24908719
TI  - Darzi's vision becomes a reality.

PMID- 24908720
TI  - Risky business.

PMID- 24908721
TI  - What do I do now?

PMID- 24908723
TI  - Stepping outside the medical treatment.

PMID- 24908722
TI  - Better statistics for better perinatal health.

PMID- 24908724
TI  - Home from home.

PMID- 24908725
TI  - A day in the life of ... a specialist bereavement midwife.

PMID- 24908726
TI  - [Epigenetic regulation in spermatogenesis].
AB  - Spermatogenesis is a process consisting of spermatogonial proliferation,
      spermatocytic meiosis, and spermiogenesis, and is also considered to be a process
      in which heterochromatins gradually aggregate and finally reach a highly
      condensed formation in the sperm head. Recent studies show that epigenetic
      regulation plays a key role in spermatogenesis. This review discusses the
      mechanisms of epigenetic regulation in spermatogenesis in three aspects, DNA
      methylation, histone modification, and noncoding RNAs. These factors are
      essential for spermatogenesis, fertilization, and embryogenesis by mutual
      regulation as well as by gene expression regulation, transposon activation, sex
      chromosome inactivation, and genome imprinting.

PMID- 24908727
TI  - [Screening lentiviral vectors carrying effective siRNA of the ROCK2 gene].
AB  - OBJECTIVE: To screen the lentiviral vector carrying siRNA and capable of
      significantly suppressing the ROCK2 gene expression in the corpus cavernosum
      smooth muscle cells of spontaneously hypertensive rats (SHR). METHODS: We
      designed and synthesized 4 siRNA fragments targeting the ROCK2 gene and packaged
      them into lentiviral vectors. We collected corpus cavernosum smooth muscle cell
      samples from 5 male SHRs and randomly divided them into groups A (non
      transfection control), B (GFP lentiviral transfection), C, D, E, and F
      (lentiviral transfection with siRNA fragments 1 -4 targeting the ROCK2 gene).
      Each group consisted of 5 samples and each sample 3 x 10(4) cells. At 48 hours
      after transfecting MOI = 80 into the SHR corpus cavernosum smooth muscle cells,
      we detected the expression of GFP under the fluorescent microscope and the mRNA
      expression of the ROCK2 gene by RT-PCR. RESULTS: The transfection efficiency of
      the SHR corpus cavernosum smooth muscle cells was > 50%. Compared with group A,
      the expression of ROCK2 mRNA in the corpus cavernosum smooth muscle cells showed
      no remarkable change in group B (P > 0.05) but was inhibited very significantly
      in C ([43.91 +/- 8.19]%), D ([47.15 +/- 6.64]%), and F ([25.7 +/- 6.03]%) (P <
      0.01), and significantly in E ([16.81 +/- 5.94]%, P < 0.05). CONCLUSION: We
      successfully constructed 4 lentiviral vectors carrying siRNA targeting the ROCK2
      gene, all of which can significantly suppress the ROCK2 expression in the SHR
      corpus cavernosum smooth muscle cells, and one has a highly strong inhibitory
      effect.

PMID- 24908728
TI  - [Total flavonoids of litsea coreana decreases the cytotoxicity of oxaliplatin in
      TM3 Leydig cells via enhancing the function of gap junction].
AB  - OBJECTIVE: To investigate the effects of total flavonoids of Litsea Coreana
      (TFLC) on the gap junction (GJ) intercellular communication in TM3 testicular
      Leydig cells and whether TFLC can reduce the cytotoxicity of oxaliplatin (OHP) in
      vitro. METHODS: We detected the effect of TFLC on the dye spread of the in vitro
      cultured TM3 cells by parachute assay, observed changes in the expression of
      connexin 43 (Cx43) total protein in the TFLC-treated TM3 cells by Western blot,
      and determined the effects of TFLC on the expression of Cx43 on the membrane of
      the TM3 cells by immunofluorescence assay and on the cytotoxicity of OHP by MTT
      assay. RESULTS: TFLC obviously enhanced the GJ function with the increasing of
      the TFLC concentration in the TM3 cells. Western blot and immunofluorescence
      assay confirmed that TFLC significantly enhanced the expression of Cx43 total
      protein and Cx43 expression on the membrane of the TM3 cells. MTT assay showed
      that at a high cell density (confluent with GJ formation), 20 microg/ml TFLC
      enhanced the GJ function of the TM3 cells and reduced the cytotoxicity of OHP (P
      < 0.05), while at a low density (preconfluent with no GJ formation), TFLC
      exhibited no effect on the cytotoxicity of OHP (P > 0.05). CONCLUSION: TFLC
      increases the Cx43 expression and GJ function in normal TM3 Leydig cells, and the
      enhancement of GJ function reduces the cytotoxicity of OHP.

PMID- 24908729
TI  - [Low-dose nonylphenol promotes the proliferation of DU-145 cells and expression
      of membrane estrogen receptor GPR30 in DU-145 cells].
AB  - OBJECTIVE: To observe the effects of low-dose exogenous estrogen nonylphenol (NP)
      on the proliferation of human prostate cancer cell lines DU-145 and the
      expression of the membrane estrogen receptor GPR30 in the DU-145 cells. METHODS:
      We exposed DU-145 cells to different concentrations of NP for 24 hours, followed
      by measurement of the half maximal inhibitory concentration (IC50) of the cells
      by cell proliferation assay and determination of the concentration of exposure to
      low-dose NP. We also observed the expressions of 3 estrogen receptors (ER),
      including ER-alpha, ER-beta and membrane estrogen receptor GPR30, in the DU-145
      cells exposed to low-dose NP by RT-PCR. RESULTS: Cell proliferation assay showed
      that within a certain range of doses, NP inhibited the proliferation of the DU
      145 cells with an IC50 of 46 micromol/L, a much lower dose of NP than IC50, 0.01,
      0.1.1 micromol/l NP, that can promote the proliferation of DU-145 cells. The
      results of RT-PCR indicated that the expressions of the three ERs in the DU-145
      cells were similar to those in prostate epithelial cells, and that low-dose NP
      promoted the expression of GPR30. CONCLUSION: Membrane estrogen receptor GPR30
      may play a role in low-dose NP promoting the proliferation of DU-145 cells.

PMID- 24908730
TI  - [Advanced glycation end products inhibit testosterone production in rat Leydig
      cells].
AB  - OBJECTIVE: To study the expression of the receptor for advanced glycation end
      products (RAGE) and the inhibitory effect of advanced glycation end products
      (AGEs) on testosterone production in rat Leydig cells. METHODS: Rat Leydig cells
      were primarily cultured and the expression of RAGE in the Leydig cells was
      detected by RT-PCR and immunofluorescence staining. The Leydig cells were treated
      with AGEs at the concentrations of 25, 50, 100 and 200 microg/ml, respectively,
      and the testosterone content was determined by ELISA. RESULTS: RT-PCR and
      immunofluorescence staining exhibited the expression of RAGE in the rat Leydig
      cells. AGEs remarkably suppressed hCG-induced testosterone production in the
      Leydig cells in a concentration-dependent manner in the 50, 100 and 200 microg/ml
      groups as compared with the control (P < 0.01). CONCLUSION: RAGE exists in rat
      Leydig cells and AGEs can significantly inhibit the secretion of testosterone in
      primarily cultured rat Leydig cells.

PMID- 24908731
TI  - [Establishment of a rat model of autoimmune prostatitis with purified prostatic
      proteins].
AB  - OBJECTIVE: To establish a rat model of autoimmune prostatitis using purified
      prostatic proteins (PPP). METHODS: Thirty-six male Wistar rats were randomized
      into three groups of equal number to receive intramuscular injection of normal
      saline (normal control group) and PPP at 15 mg/ml (low-concentration group) and
      80 mg/ml (high-concentration group). At 4 weeks after modeling, the rats were
      sacrificed for HE staining of the prostate tissue and examination of the
      inflammatory factors IL-8 and IL-10 in the serum, immunoglobulins IgA and IgM,
      and regulatory T cells Th1/Th2. RESULTS: Three rats died in the high
      concentration PPP group but none in the low-concentration PPP and normal control
      groups. Gross observation of the prostate showed increased volume and hard
      texture of the prostate in the two PPP groups, but no significant change in the
      normal controls. Pathological examination exhibited morphological damage to the
      prostatic tissue and inflammatory cellular infiltration in the experimental rats.
      The serum level of IL-8 was significantly higher in the low- and high
      concentration PPP groups ([129.07 +/- 11.48] and [147.58 +/- 17.70] pg/ml) than
      in the control ([94.12 +/- 7.04] pg/ml) (P < 0.05), while that of IL-10 was
      remarkably lower in the former two groups ([227.14 +/- 18.19] and [187.14 +/-
      16.32] pg/ml) than in the latter ([252.48 +/- 21.72] pg/ml, P < 0.05). The serum
      level of IgA was markedly elevated in the low- and high-concentration PPP groups
      as compared with that in the control ([0.25 +/- 0.37] and [0.31 +/- 0.42] vs
      [0.19 +/- 0.14] mg/ml, P < 0.05), and so was that of IgM ([0.23 +/- 0.41] and
      [0.34 +/- 0.58 ] vs [0.17 +/- 0.33] mg/ml, P < 0.05). No significant changes were
      observed in the levels of regulatory T cells Th1/Th2. CONCLUSION: Both low and
      high concentrations of purified prostatic proteins can be used for the
      construction of autoimmune prostatitis models in rats, while low concentration is
      preferable for its advantages of lower mortality of the rats and inducement of
      more consistent manifestations of autoimmune prostatitis.

PMID- 24908732
TI  - [Relationship between ERCC2 single nucleotide polymorphisms and male idiopathic
      infertility in Ningxia].
AB  - OBJECTIVE: To explore the influence of the DNA repair gene ERCC2 single
      nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male
      idiopathic infertility in Ningxia, China. METHODS: Using MassArray, we conducted
      a case-control study and genotyped three ERCC2 SNPs rs13181, rs1618536, and
      rs1799793 for 351 males (aged 31.0 +/- 4.2 years) with idiopathic infertility and
      another 327 normal fertile men (aged 33.0 +/- 5.9 years) as controls. RESULTS:
      The ERCC2 AnyG-anyA-anyA genotypes were significantly associated with an
      increased risk of idiopathic infertility (OR 0.414, 95% CI 0.176 - 0.970), while
      the three single ERCC2 SNPs rs13181, rs1618536, and rs1799793 showed no
      significant differences between the cases and controls (P > 0.05). CONCLUSION:
      The ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in
      male idiopathic infertility in Ningxia, contributing to the risk of the disease.

PMID- 24908733
TI  - [Improved sample collection methods and bacteriologic localization patterns for
      male genital tract infection].
AB  - OBJECTIVE: To improve the sample collection methods and bacteriologic
      localization patterns in male genital tract infection, and to investigate the
      influence of specimen collection and pathogen isolation on the diagnosis and
      treatment of prostatitis. METHODS: We collected the samples of the initial
      urinary stream, the third portion of the urinary stream, expressed prostatic
      secretion (ESP), and semen from 200 adult males with chronic prostatitis-like
      symptoms, inoculated them quantitatively in culture media for isolation of
      microorganisms, and evaluated their laboratory diagnostic significance according
      to the count of colonies and distribution of the isolates. RESULTS: A total of
      468 strains of microorganisms were isolated from the samples, including 414
      strains of bacteria spp (88.5%), 12 strains of fungi spp (2.6%), 40 strains of
      mycoplasma spp (8.5%), and 2 strains of chlamydia spp (0.4%). Pathogens were
      isolated from the ESP in 66 cases (33.0%), from the semen in 34 cases (17.0%),
      and from both the ESP and semen in 100 cases (50.0%). Only 1 species of pathogen
      was found in the ESP samples of 36 cases (18.0%), in the semen samples of 20
      cases (10%), and in both the ESP and semen samples of 39 cases (19.5%); 2 species
      in the ESP samples of 30 cases (15.0%), in the semen samples of 14 cases (7.0%),
      and in both the ESP and semen samples of 60 cases (30.0%); and 3 species in both
      the ESP and semen samples of 1 case (0.5%). CONCLUSION: Multiple microbial
      infection (MMI), multi-organ infection (MOI) and drug-resistance strains
      infection are common in patients with prostatitis-like symptoms, frequently
      leading to missed diagnosis and misdiagnosis in clinic and laboratory, and
      affecting the effect of antimicrobial therapy. MMI and MOI can be diagnosed and
      differentially diagnosed with the improved sample collection methods and
      bacteriologic localization patterns.

PMID- 24908734
TI  - [Suprapubis-assisted umbilical laparoendoscopic mini-dual-site surgery for
      varicocele: a report of 80 cases].
AB  - OBJECTIVE: To study the safety, effectiveness and feasibility of suprapubis
      assisted umbilical laparoendoscopic mini-dual-site surgery (SAU-LEMDS) in the
      treatment of varicocele. METHODS: This study included 80 varicocele patients aged
      24 - 44 (mean 28.5 +/- 2.6) years, 25 cases of grade I, 45 cases of grade II and
      10 cases of grade III, 58 cases in the left side, 6 in the right and 16 in both
      sides, and all with asthenospermia. The patients were treated by SAU-LEMDS under
      subarachnoid anesthesia combined with general anesthesia in a supine position
      with a head-down-feet-up slope of 15 degrees. Two 5 mm trocars were inserted
      bilaterally at the umbilical edge, one with a 5 mm 30 degrees laparoscope placed
      in it, and another into the abdominal cavity below the pubic hairline with a 5 mm
      laparoendoscopic clipper placed in it. The operation procedure was similar to
      that of standard laparoscopic ligation of spermatic veins, with reservation of
      the spermatic artery and double-ligation of spermatic veins. And the procedure
      was repeated for the contralateral lesion in the bilateral cases. Postoperative
      follow-up was conducted for the incidences of orchiatrophy and testicular
      hydrocele and changes of seminal parameters. RESULTS: All the operations were
      successful, with the mean operation time of (10 +/- 5.0) min (range 8 to 25 min)
      for the unilateral cases and (18 +/- 6.5) min (range 15 to 30 min) for the
      bilateral cases, the mean blood loss of (1.5 +/- 0.5) ml (range 1 to 2 ml), and
      the mean postoperative hospital stay of (2 +/- 0.5) d (range 1.5 to 3 d). The
      patients were followed up for 6 -24 (12 +/- 2.5) months, which showed significant
      improvement in sperm motility as compared with the baseline ([28.53 +/- 5.21] vs
      [19.62 +/- 3.56]%, P < 0.05), with 28 cases (35.0%) restored to normal.
      Recurrence was found in 4 cases (5.0%). Testicular hydrocele occurred in 7 cases
      (8.75%), but orchiatrophy in none. The scars in the umbilicus and suprapubis were
      invisible because of the wrinkles and pubic hair. CONCLUSION: SAU-LEMDS is safe,
      effective and feasible for the treatment of varicocele. It is superior to
      umbilical laparoendoscopic single-site surgery (U-LESS) for its less
      invasiveness, simpler operation, and better cosmetic appearance.

PMID- 24908735
TI  - [Primary testicular yolk sac tumor: clinicopathological study of 8 cases].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis and
      treatment of primary testicular yolk sac tumor (YST). METHODS: We studied 8 cases
      of primary testicular YST by microscopy and immunohistochemistry. RESULTS: The 8
      cases of primary testicular YST, including 2 consultation cases, were confirmed
      from 1998 to 2013, accounting for 10.7% (8/75) of all the testicular germ cell
      tumors diagnosed in our hospital. The patients ranged in age from 7 to 43 years,
      23.9 years on average. The main clinical manifestation of the patients was
      painless unilateral testis swelling. Microscopically, reticular tissues, schiller
      duvaI (S-D) bodies, and eosin-stain transparent bodies were seen in the tumors.
      One of the cases was confirmed to be simple YST, while the other 7 mixed YST. AFP
      was a characteristic immunophenotype marker of the tumors. CONCLUSION: Primary
      testicular YST is a rare malignancyr with poor prognosis. Its diagnosis depends
      on preoperative AFP test and postoperative pathology. Comprehensive treatment,
      including orchiectomy, chemotherapy, and radiotherapy, can prolong the survival
      of the patients.

PMID- 24908736
TI  - [Foley catheter versus urethral stent plus gastric tube for urine drainage
      following urethroplasty].
AB  - OBJECTIVE: To compare the advantages and disadvantages of the Foley catheter
      draining method versus the urethral stent plus gastric tube draining method for
      urine drainage following urethroplasty for hypospadias. METHODS: We
      retrospectively analyzed the clinical data of 361 cases of hypospadias treated by
      urethroplasty. After operation, 91 of the cases received urine drainage with the
      Foley catheter (group A) and 270 with a urethral stent plus a gastric tube (group
      B). We compared the incidence rates of bladder irritation, fistula, urethral
      stricture, and urethral diverticulum between the two groups of patients. RESULTS:
      No statistically significant differences were found between groups A and B in the
      incidences of bladder irritation (9.89% vs 10.70%, P > 0.05) and urethral
      diverticulum (1.09% vs 2.22%, P > 0.05). The incidence rate of fistula was
      markedly higher in group A than in B (20.80% vs 13.30%, P < 0.05), and so was
      that of urethral stricture (10.90% vs 5.55%, P < 0.05). CONCLUSION: The urethral
      stent plus gastric tube draining method is more effective than the Foley catheter
      draining method for urine drainage following urethroplasty.

PMID- 24908737
TI  - [Therapeutic efficacy of compound Xuanju capsule on autoimmune prostatitis in
      rats: an experimental study].
AB  - OBJECTIVE: To evaluate the therapeutic effect of Compound Xuanju Capsule (CXC) on
      autoimmune prostatitis in rat models. METHODS: Sixty healthy male Wistar rats
      were randomly divided into five groups of equal number: blank control, low
      concentration purified prostate protein (low-conc PPP), low-conc PPP + CXC
      treatment, high-concentration PPP (hi-con PPP), and hi-conc PPP + CXC treatment.
      Autoimmune prostatitis models were established by intragastric administration of
      PPP solution at 15 mg/ml (low concentration) and 80 mg/ml, respectively. At 30
      days after modeling, the rats in the blank control and low-conc and hi-conc PPP
      model groups were treated with normal saline, and those in the other two groups
      with CXC at a daily dose of 0.068 g/ml. At 30, 45, and 60 days, all the animals
      were sacrificed for observation of pathological changes in the prostate tissue
      and determination of the levels of IL-8, IL-10, and TNF-alpha in the serum.
      RESULTS: Compared with the PPP models, the hi-conc PPP + CXC group showed
      significantly reduced levels of IL-8 and TNF-alpha in the serum at 45 days
      ([148.54 +/- 17.23] and [62.14 +/- 5.59] pg/ml vs [100.77 +/- 11.08] and [32.63
      +/- 2.91] pg/ml, P < 0.05) and at 60 days ([143.69 +/- 17.28] and [59.38 +/-
      5.50] pg/mlvs [95.77 +/-10.53] and [29.63 +/- 2.66] pg/ml, P < 0.05), and so did
      the low-cone PPP + CXC group at 45 days ([128.47 +/- 12.21] and [40.43 +/- 3.64]
      pg/ml vs [111.76 +/- 10.07] and [35.44 +/- 3.17] pg/ml, P < 0.05) and at 60 days
      ([131.07 +/- 10.93] and [43.34 +/- 3.91] pg/ml vs [97.46 +/- 8.75] and [30.44 +/-
      2.75] pg/ml, P < 0.05). The serum level of IL-10 was remarkably elevated in the
      hi-cone PPP + CXC group as compared with that of the PPP models at 45 and 60 days
      ([189.14 +/- 16.78] and [184.14 +/- 15.89] pg/ml vs [230.48 +/- 29.96] and
      [248.48 +/- 31.03] pg/ml, P < 0.05), and so was it in low-cone PPP + CXC group
      ([223.14 +/- 17.87] and [224.14 +/- 17.93] pg/ml vs [231.42 +/- 23.18] and
      [249.42 +/- 24.97] pg/ml, P < 0.05). Pathological examination revealed
      morphological damages to the prostate tissue and infiltration of inflammatory
      cells in the model rats, but no obvious changes in the normal controls. At 15
      days of treatment, the rats in the PPP + CXC group showed enlarged prostate
      glandular cavity, mild proliferation of epithelial cells, no obvious infiltration
      of inflammatory cells in the interstitial tissue, and a few visible fibrous
      tissues under the light microscope. CONCLUSION: Compound Xuanju Capsule is
      efficacious on autoimmune prostatis in rats by reducing inflammatory changes in
      the prostate tissue and improving the expression of inflammatory factors.

PMID- 24908738
TI  - [Compound Xuanju capsule for type III and type IV prostatitis: observation of
      therapeutic results].
AB  - OBJECTIVE: To investigate the efficacy and action mechanisms of Compound Xuanju
      Capsule (CXC) in the treatment of type III and type IV prostatitis. METHODS: This
      study included 88 cases of type III and 18 cases of type IV prostatitis, 14 with
      male infertility, 27 with ED, and 8 with increased PSA levels. In addition to
      prostate massage and psychotherapy, the patients were treated with CXC, 3
      capsules once, tid, for 3 months. Then changes in relevant indexes were evaluated
      by the self-control method. RESULTS: The NIH-CPSI scores of the patients with
      type III prostatitis were decreased by 47.59% (22.17 +/- 3.48 vs 1.62 +/- 2.53)
      after 1 month and by 74.61% (22.17 +/- 3.48 vs 5.63 +/- 3.14) after 3 months of
      CXC medication, with statistically significant differences from the baseline in
      both the total score and the scores on specific items (P < 0.05). The patients
      with infertility showed significantly improved sperm quality after treatment as
      compared with premedication (sperm cone: [12.52 +/- 3.16] x 10(6)/ml vs [28.32 +/
      8.36] x 10(6)/ml, grade a sperm: [10.12 +/- 4.56]% vs [26.06 +/- 10.18]%, grade
      a + b sperm: [29.89 +/- 8.86]% vs [53.26 +/- 11.29]%) (P < 0.05), and 8 of the
      patients' spouses got pregnant. Nineteen of the patients with ED were cured, with
      significant differences in the IIEF-5 score from pretreatment (10.41 +/- 3.65 vs
      19.78 +/- 3.00) (P < 0.05). The PSA level was reduced to normal in all the 8
      abnormal cases. The WBC count was remarkably decreased and even returned to
      normal in 19 cases with WBC count > 100/HP ative culture results. CONCLUSION:
      Compound Xuanju Capsule is efficacious for type III and type IV prostatitis and
      those complicated by infertility, ED, PSA elevation, WBC increase, and negative
      culture results, with no obvious adverse events.

PMID- 24908739
TI  - [Application of microfluidics in sperm isolation and in vitro fertilization].
AB  - Due to the low effectiveness of traditional assisted reproductive technology
      (ART), new technological possibilities are constantly explored. Lots of studies
      have demonstrated the potential of microfluidics to revolutionize the fundamental
      processes of in vitro fertilization (IVF). With the advantages of high
      efficiency, short time, harmless collection, real-time observation of separation,
      similar microenvironment, and automation, the application of microfluidics in
      sperm isolation and IVF has shown an evident superiority over the conventional
      approaches and provided a new platform for ART. This review highlights the
      application of various microfluidic techniques in sperm motility assessment and
      isolation, sperm chemotaxis assay, IVF, sperm concentration, and sperm separation
      and enrichment in recent years. It also briefly introduces the basic principles,
      structural design, and operation processes of the microfluidic platform, focusing
      on the advantages and disadvantages of each method and the potential of their
      clinical application. Obviously, there are still some challenges to the
      application of microfluidics in ART. However, it is believed that the development
      of this new technology would be toward a highly integrated application of several
      steps in one single device, known as IVF-lab-on-a-chip.

PMID- 24908740
TI  - [Prostate stem cells: an update].
AB  - Stem cells are characterized by self-renewing, multipotent differentiation, and
      high proliferation and receiving more and more attention for their roles in the
      development and management of various diseases. There are epithelial stem cells
      and mesenchymal stem cells in the prostate. The markers of the epithelial stem
      cells include cytokeratin, stem cell antigen-1, and integrins alpha2beta1, CD49f,
      CD133, CD117, and CD44. The markers of the mesenchymal stem cells include CD30,
      CD44, CD133, neuron-specific enolase, and vascular endothelial growth factor
      receptor-1. Prostate stem cells are involved in the development and treatment of
      prostatic diseases. This review focuses on the latest progress in the studies of
      prostate stem cells.

PMID- 24908741
TI  - [Consultations for travelers: messages...but with wisdom].

PMID- 24908742
TI  - [Security: a shared concern].
AB  - During a stay abroad, travelers are exposed to dangers and threats. This is
      nothing new, and most of the risks (e.g. traffic accidents) remain the same for
      many years. Large territories have nonetheless become inaccessible due to
      political instability, national or international conflicts, terrorist threat, or
      kidnapping risk. It is thus necessary to consider the problematic of security,
      whether at the time of preparation or at the destination. Beyond the usual pre
      departure health counseling, the primary care physician may have a role to
      accompany the traveller in the management of his or her security. The aim should
      be to make travelers conscious of hazards and direct him or her towards available
      resources for planning, decision making support, and implementation of risk
      mitigation measures.

PMID- 24908743
TI  - [True and virtual risks of travellers].
AB  - Evidence-based information on travel associated mortality is scarce. Perception,
      intuition and the availability of interventions such as vaccinations and
      chemoprophylaxis often guide pre-travel advice. Important risks including
      accidents and cardiovascular events are not routinely included in pre-travel
      consultations although they cause more fatalities and costs than infectious
      diseases. The increased risk of sustaining a road accident in poor economy
      countries should always be mentioned. The general practitioner is further best
      placed to discuss possible problems of travellers with chronic diseases before
      travel.

PMID- 24908744
TI  - [New viruses: myth, fantasy or reality?].
AB  - Emerging viruses previously unknown or partially known that infect repeatedly the
      human population are more than ever in the medias actuality headlines. Multiple
      factors may explain this dynamic. The most important is certainly the rapid
      evolution and the adaptation capacity of these viruses. Note that the increase in
      travel and international trade or climate change also play an important role. On
      the other hand, laboratory tests and current surveillance systems are more
      efficient. Thus, transmission of virus from an animal reservoir to human are more
      easily detected, accentuating the feeling of increasing phenomenon. Virological
      predictions have very low reliability in epidemiology. It is a reality that we
      have to accept.

PMID- 24908745
TI  - [Emerging parasitic diseases].
AB  - Travels, migration and circulation of goods facilitate the emergence of new
      infectious diseases often unrecognized outside endemic areas. Most of emerging
      infections are of viral origin. Muscular Sarcocystis infection, an acute illness
      acquired during short trips to Malaysia, and Chagas disease, a chronic illness
      with long incubation period found among Latin American migrants, are two very
      different examples of emerging parasitic diseases. The former requires a
      preventive approach for travelers going to Malaysia and must be brought forth
      when they return with fever, myalgia and eosinophilia, while the latter requires
      a proactive attitude to screen Latin American migrant populations that may face
      difficulties in accessing care.

PMID- 24908747
TI  - [Telemedicine in your suitcase: useful tools for the traveler].
AB  - In our digital age, telemedicine becomes, under various forms, a useful companion
      for the traveler, providing access to up-to-date information about health and
      security risks, remote consultation of specialists to ascertain a diagnosis of
      select an appropriate treatment, connection to similar patients in order to
      obtain contextualized advice, biomedical sensors and other monitoring and
      diagnostic portable tools, as well as transportable electronic health records
      enabling continuity of care and mobility. Commercial telemedicine services are
      being developed specifically for travelers, most of which are using mobile phones
      as the main device, which thus becomes a real telestethoscope.

PMID- 24908746
TI  - [Yellow fever: new recommendations].
AB  - Indication for yellow fever vaccination is not always easy to assess. The
      decision to immunize is not only based on the actual risk of the disease in a
      specific location, but also on public health considerations in the visited
      country (in order to respectively avoid epidemics in endemic countries or the
      introduction of the virus in zones where the vectors mosquitoes are present) and
      on travelers' risk factors for severe or even fatal vaccine adverse events. WHO
      has recently published new recommendations regarding vaccination against yellow
      fever after concluding that one dose of vaccine generates a life-long protection.
      This article tends to clarify the strategy to adopt in 2013 using cases
      frequently encountered in the practice of travel medicine.

PMID- 24908748
TI  - [Children and pregnant women at high altitude].
AB  - Nowadays, high altitude resorts have become popular destinations for family
      vacations. Based on a limited number of publications and international
      guidelines, this article summarizes the effects of high altitude on children and
      pregnant women. Children also suffer from high altitude-related diseases, however
      their presentation and clinical significance are different from their adult
      counterparts. Careful planning of the itinerary with respect to altitude of the
      overnight stays, access to medical services and potential evacuation routes is
      the cornerstone of a successful vacation.

PMID- 24908749
TI  - [Thrombophilia: when to think of it?].

PMID- 24908750
TI  - [Death and taxes].

PMID- 24908751
TI  - [Alcohol dependence: early treatment of cognition disorders].

PMID- 24908752
TI  - [When Lithium started to calm down intense agitation].

PMID- 24908753
TI  - [Another broken-down Europe: the one of organ transplantations].

PMID- 24908754
TI  - [A virtual twin, towards the future and return].

PMID- 24908755
TI  - [Unusual discovery situation: is the cadaver position normal? Livor mortis].

PMID- 24908756
TI  - [Artificial nails: the cavities contain lively budding candida (interview by
      Christine Starostzik)].

PMID- 24908757
TI  - [Bureaucracy in routine general practice: :|"I would rather help patients"].

PMID- 24908758
TI  - [Parliament abolishes refinancing clause: finally can HZV (family practice
      centered patient care) take off in Germany].

PMID- 24908759
TI  - [Bringing health to the man: equality in preventive screening].

PMID- 24908760
TI  - [Testosterone supplementation: good feeling in the pants, pain in the chest].

PMID- 24908761
TI  - [Obstructive respiratory tract diseases: contraindications to beta blockers
      crumble].

PMID- 24908762
TI  - [Syncope in patient with pacemaker: why did the patient suddenly faint?].

PMID- 24908763
TI  - [Blood specimen collection in general practice: must patients actually be
      fasting?].

PMID- 24908764
TI  - [Your patient needs antithrombotics: leg venous thrombosis : how to proceed?].

PMID- 24908765
TI  - [Inhaled steroids increase the risk of pneumonia in asthmatics].

PMID- 24908766
TI  - [Obesity biography begins early].

PMID- 24908767
TI  - [Chocolate might reduce weight].

PMID- 24908768
TI  - [Mysterious bubble in diabetic foot].

PMID- 24908769
TI  - [Nail in the head-so what?].

PMID- 24908770
TI  - [Compression stockings can not prevent post-thrombotic syndrome].

PMID- 24908771
TI  - [ACE inhibitor in aortic stenosis is not dangerous, but useful].

PMID- 24908772
TI  - [Taking tongue lumps seriously].

PMID- 24908773
TI  - [Skin cancer: it's worth it to take a look!].

PMID- 24908774
TI  - [Early detection of skin cancer].

PMID- 24908775
TI  - [Current therapeutic strategies for cutaneous malignancies].

PMID- 24908776
TI  - [Yellow penile papules--ectopic sebaceous glands].

PMID- 24908777
TI  - [Dehydration and subcutaneous infusion (hypodermoclysis) in the elderly].

PMID- 24908778
TI  - [Pharmacotherapy and diagnosis of allergic rhinitis].

PMID- 24908779
TI  - [Interventions to enhance adherence to medication].

PMID- 24908780
TI  - [Diabetic foot syndrome: diabetic foot must have optimal treatment].

PMID- 24908781
TI  - [Interview with Dr. Michael Huptas, established diabetologist, Essen: inadequate
      blood glucose regulation increases the risk (interview by Roland Fath)].

PMID- 24908782
TI  - [The bodies of dwarfs in Italian art during the Renaissance].
AB  - Agnolo Bronzino's painting of Nano Morgante depicts for the first time the
      anatomy of a dwarf. This image testifies Cosimo's special interest for this
      dwarf. In Antonio Francesco Grazzini's poem written in Nano Morgante's honor, we
      underline some interesting aspects of his physical deformities and his small
      height, which are highly praised as we can see them on the painting.

PMID- 24908783
TI  - [Ryoun Takamatsu (1837-1916). The first Japanese physician to have studies modern
      medicine in France].
AB  - Ryoun Takamatsu, born in Japan in 1837, was a member of the delegation to the
      Universal Exposition 1867 in Paris. He worked as a trainee in the Hotel-Dieu of
      Paris. After returning to Japan, he practiced and spread the modern technical and
      spiritual cares and cures he had learnt in France.

PMID- 24908784
TI  - [A delicate and life saving appendectomy].
AB  - An appendectomy which was practiced in the camp of Dachau to save the life of one
      of the torturers looks like a dangerous wager and the writer shows how a good
      surgeon could win the bet through his skillfulness and save life of his comrades
      and his own.

PMID- 24908785
TI  - [Military physician Colonel Robert Yout. Twenty years as a paratrooper medical
      officer].
AB  - Robert Yout was born on June 15th, 1930. A rugby player and a member of the
      French Volleyball team, he was already an outstanding sportsman when he began his
      studies at the Health Services School in Lyons. His career as an army medical
      officer among the paratroopers was atypical. He spent many years among the most
      prestigious elite paratroopers of the French army: the 2nd REP, the 1st CHOC and
      the CINC (The Army Training School for Combat Swimmers) . When he retired, he was
      Head Doctor of the Paratroopers parent company: The Airborne School of Pau. For
      the army medical historian, Robert Yout is the perfect example of a man with an
      outstanding and remarkable career: A crack soldier, a brave army medical officer,
      a parachuting and diving pioneer and a sportsman of international class.

PMID- 24908786
TI  - [The history of commensalism: a contemporary history of microbiology].
AB  - Commensalism is a biological association between two species, with one species,
      the commensal, getting an advantage, whereas the other one, the host, gets no
      advantage neither disadvantage. This concept is theorized in the 1860's by Pierre
      Joseph Van Beneden. Van Beneden is a physician in the 1850's, nevertheless, he is
      well known as a zoologist. The concept of commensalism developed by Van Beneden
      is employed in many scientific fields, not only in zoology, but also, in
      microbiology. Although the use of a possible play of the commensal bacterial
      microflora is exposed at the end of the 19th century, it is only during the
      second part of the 20th century that this way is studied. Commensalism in animal
      microbiology is studied first and then it is studied in human. The aim of this
      article is to present the history of commensalism as a main part of the history
      of microbiology.

PMID- 24908787
TI  - [Egyptian medicine at the time of Bonaparte's expeditionary force].
AB  - When the civils of the Commission for Sciences and Arts and the doctors from
      Bonaparte's expeditionary forces under Desgenettes and Larrey's orders arrived in
      Egypt, they described richly the state of medecine and surgery, the therapeutical
      knowledges and the medical organisation of the conquered land. They were
      surprised at first and desappointed to see how poorly Herophile and Ibn-An-Nafis'
      "Art of Healing" was considered. However they quickly managed to extract its most
      original qualities - in particular in the pharmacopoeia--all the more because the
      loss of the hospital-ships and Aboukir's defeat forced them to stay in Egypt and
      to find there the remedies they were lacking of.

PMID- 24908788
TI  - [When the scientific career favors the scholarly diffusion of innovation: doctor
      Max Fourestier].
AB  - In 1992, the hospital of Nanterre assumed Max Fourestier's surname, as this great
      doctor was in office there between 1948 and 1973. Max Fourestier's biography and
      career emphasize that he embarked on three specific professional fields :
      specialty medicine, social medicine and school medicine. At the time, Max
      Fourestier was developing his universal endoscope in his department in Nanterre,
      achieving an extensive experience of massive BCG vaccination in a tuberculosis
      clinic in Montreuil, called "social hygiene" and, finally, carrying out a lot of
      school innovations to achieve an equal division of time between school work and
      sport practices. He also implemented snow classes in public schools in 1953 or
      napping classes,forest classes and snow classes in infant schools in 1959. In
      short, this presentation reveals that the inherent process of Max Fourestier's
      school innovation reputation lies in the scientific will of its creator, which
      allows him to convey his teaching ideas at the international level. Finally, in
      addition to the inventory of the physician's various innovations, the major
      challenge of this presentation is to reveal the intertwining and strong
      connections of Max Fourestier's medical and school commitments. In 1992, the
      hospital of Nanterre assumed Max Fourestier's surname, as this great doctor was
      in office there between 1948 and 1973. Max Fourestier's biography and career
      emphasize that he embarked on three specific professional fields: specialty
      medicine, social medicine and school medicine. At the time, Max Fourestier was
      developing his universal endoscope in his department in Nanterre, achieving an
      extensive experience of massive BCG vaccination in a tuberculosis clinic in
      Montreuil, called "social hygiene" and,finally, carrying out a lot of school
      innovations to achieve an equal division of time between school work and sport
      practices. He also implemented snow classes in public schools in 1953 or napping
      classes, forest classes and snow classes in infant schools in 1959. In short,
      this presentation reveals that the inherent process of Max Fourestier's school
      innovation reputation lies in the scientific will of its creator, which allows
      him to convey his teaching ideas at the international level. Finally, in addition
      to the inventory of the physician's various innovations, the major challenge of
      this presentation is to reveal the intertwining and strong connections of Max
      Fourestier's medical and school commitments.

PMID- 24908789
TI  - [The contribution of Louis-Bernard Guyton de Morveau (1737-1816) to public health
      and the adoption of his ideas in the Netherlands].
AB  - In the early 19th century the concept of miasmata played a leading role in the
      explanation of contagious diseases and epidemics. Furthermore the new chemistry,
      developed by Lavoisier and his colleagues, facilitated the introduction of a new
      way of disinfecting the air and destroying contagious substances. These facts
      facilitated the introduction of a new way of fighting disease carriers, whatever
      their nature might be, by means of fumigations. These treatments were carried out
      by means of disinfecting vaporous agents, produced by mixing mineral acids with
      sodium chloride and manganese peroxide. In 1801 Guyton-Morveau published a book
      on this subject, which in 1802 appeared in a Dutch enlarged edition. The
      Netherlands were in urgent need of an effective means of fighting disease
      carriers, since its coastal areas were frequently stricken by epidemics. The
      French government, incited by the Institut National, the Conseil de Sante and the
      Ecole de Medecine de Paris, gave top priority to the introduction of Guyton's
      salutary operation in France. In 1814 the Dutch Society of Sciences held a
      contest about the applicability and effects of the fumigations invented by Guyton
      Morveau. In 1823, two entries were received, one of which was awarded the gold
      medal. It turned out to have been written by the translator of Guyton's book,
      published in 1801.

PMID- 24908790
TI  - [A new look at the tomb of the physician, Morlongo Venice].
AB  - The development of the inventory and synthetic study of collyrium stamps,
      commonly known as "oculist's stamps", includes the physico-chemical analysis of
      rare stamped collyrium's remains. The fragments of collyrium which were
      discovered in a tomb of Morlungo (Veneto) are all the more remarkable as the
      remedy's name stamped on two of them remains enigmatic at the moment and because
      of the association in a funerary context with an-other thirty-five finds. More
      specifically, they were discovered near surgical bronze instruments, a large
      amount of amber, a portable sundial and a seal box. Recent archaeological,
      textual and technological data thus make the study of the remains of collyriums
      of Morlungo particularly interesting for the history of medicine.

PMID- 24908791
TI  - [The tourniquet of Jean-Louis Petit].
AB  - In the early part of the 18th century the mechanization of Petit's tourniquet is
      one of the most outstanding medical inventions. During more than a century that
      tool without any noticeable change was in the surgical boxes in all countries. As
      the mechanic Peron has been intensely working to handcraft the device with the
      utmost urgency Petit's tourniquet could have become that of Petit and Peron.

PMID- 24908792
TI  - [The six final International Sanitary Conferences of 1892 to 1926, the basis of
      the World Health Organization].
AB  - The authors report the contributions of the last six sanitary conferences from
      1886 to 1926. All of them, from 1851 to 1926, were the first roots of WHO.

PMID- 24908793
TI  - [Sixty years of HeLa cell cultures].
AB  - HeLa cells line was established in 1951 from cervical cancer cells taken from a
      young AfroAmerican patient, Henrietta Lacks, used without the permission of the
      family. Finally, in 2013, an agreement was established between the family and
      NIH: for any study, authorization is needed, first referred to a working group
      comprising scientists, ethicists and two members of the family.

PMID- 24908794
TI  - Listening in circles. Spoken drama and the architects of sound, 1750-1830.
AB  - The establishment of the discipline of architectural acoustics is generally
      attributed to the physicist Wallace Clement Sabine, who developed the formula for
      reverberation time around 1900, and with it the possibility of making calculated
      prognoses about the acoustic potential of a particular design. If, however, we
      shift the perspective from the history of this discipline to the history of
      architectural knowledge and praxis, it becomes apparent that the topos of 'good
      sound' had already entered the discourse much earlier. This paper traces the
      Europe-wide discussion on theatre architecture between 1750 and 1830. It will be
      shown that the period of investigation is marked by an increasing interest in
      auditorium acoustics, one linked to the emergence of a bourgeois theatre culture
      and the growing socio-political importance of the spoken word. In the wake of
      this development the search among architects for new methods of acoustic research
      started to differ fundamentally from an analogical reasoning on the nature of
      sound propagation and reflection, which in part dated back to antiquity. Through
      their attempts to find new ways of visualising the behaviour of sound in enclosed
      spaces and to rethink both the materiality and the mediality of theatre
      auditoria, architects helped pave the way for the establishment of architectural
      acoustics as an academic discipline around 1900.

PMID- 24908795
TI  - Barrow, Leibniz and the geometrical proof of the fundamental theorem of the
      calculus.
AB  - In 1693, Gottfried Wilhelm Leibniz published in the Acta Eruditorum a geometrical
      proof of the fundamental theorem of the calculus. It is shown that this proof
      closely resembles Isaac Barrow's proof in Proposition 11, Lecture 10, of his
      Lectiones Geometricae, published in 1670. This comparison provides evidence that
      Leibniz gained substantial help from Barrow's book in formulating and presenting
      his geometrical formulation of this theorem. The analysis herein also supports
      the work of J. M. Child, who in 1920 studied the early manuscripts of Leibniz and
      concluded that he had frequently copied his diagrams from Barrow's book, but
      without acknowledgement. It is also shown that the diagram of Leibniz associated
      with his 1693 proof has often been reproduced with errors that make some aspects
      of his text difficult to comprehend.

PMID- 24908796
TI  - International scientific cooperation during the 1930s. Bruno Rossi and the
      development of the status of cosmic rays into a branch of physics.
AB  - During the 1920s and 1930s, Italian physicists established strong relationships
      with scientists from other European countries and the United States. The career
      of Bruno Rossi, a leading personality in the study of cosmic rays and an Italian
      pioneer of this field of research, provides a prominent example of this kind of
      international cooperation. Physics underwent major changes during these turbulent
      years, and the traditional internationalism of physics assumed a more
      institutionalized character. Against this backdrop, Rossi's early work was
      crucial in transforming the study of cosmic rays into a branch of modern physics.
      His friendly relationships with eminent scientists--notably Enrico Fermi, Walther
      Bothe, Werner Heisenberg, Hans Bethe, and Homi Bhabha--were instrumental both for
      the exchange of knowledge about experimental practices and theoretical
      discussions, and for attracting the attention of physicists such as Arthur
      Compton, Louis Leprince-Ringuet, Pierre Auger and Patrick Blackett to the problem
      of cosmic rays. Relying on material from different archives in Europe and the
      United States, this case study aims to provide a glimpse of the intersection
      between national and international dimensions during the 1930s, at a time when
      the study of cosmic rays was still very much in its infancy, strongly interlaced
      with nuclear physics, and full of uncertain, contradictory, and puzzling results.
      Nevertheless, as a source of high-energy particles it became a proving ground for
      testing the validity of the laws of quantum electrodynamics, and made a
      fundamental contribution to the origins of particle physics.

PMID- 24908797
TI  - Managing the technological edge: the UNESCO International Computation Centre and
      the limits to the transfer of computer technology, 1946-61.
AB  - The spread of the modern computer is assumed to have been a smooth process of
      technology transfer. This view relies on an assessment of the open circulation of
      knowledge ensured by the US and British governments in the early post-war years.
      This article presents new historical evidence that question this view. At the
      centre of the article lies the ill-fated establishment of the UNESCO
      International Computation Centre. The project was initially conceived in 1946 to
      provide advanced computation capabilities to scientists of all nations. It soon
      became a prize sought by Western European countries like The Netherlands and
      Italy seeking to speed up their own national research programs. Nonetheless, as
      the article explains, the US government's limitations on the research function of
      the future centre resulted in the withdrawal of European support for the project.
      These limitations illustrate the extent to which US foreign science policy could
      operate as (stealth) industrial policy to secure a competitive technological
      advantage and the prospects of US manufacturers in a future European market.

PMID- 24908798
TI  - [Good reasons for considering new management models in health care].

PMID- 24908799
TI  - [Physicians need more pharmaceutical knowledge].

PMID- 24908800
TI  - [Secure the electronic journal! Better e-record systems can help to improve
      patient safety].

PMID- 24908801
TI  - [Electronic health records risk patient safety. Audit of medical records shows
      serious deficiencies in documentation].

PMID- 24908802
TI  - [Anticoagulation in acute stroke with atrial fibrillation. Five questions should
      be answered before the treatment can be considered evidence-based].

PMID- 24908803
TI  - [Urinary incontinence in the elderly can be treated--lack of knowledge about
      frail elderly].

PMID- 24908804
TI  - [Shoulder fractures, Part 1: Clavicular fractures].

PMID- 24908805
TI  - [The Swedish Medical Association should take a stand against market management in
      health care].

PMID- 24908806
TI  - [Restrictions misses the goal of equal care].

PMID- 24908807
TI  - [Guidelines for cholesterol treatment--the obstacle remains in Stockholm].

PMID- 24908808
TI  - [To signal benevolence].

PMID- 24908809
TI  - [Clinical features of pulmonary Mycobacterium avium complex disease diagnosed
      through gastric aspirate culture].
AB  - OBJECTIVES: The diagnostic significance of gastric aspirate culture has been
      established in pulmonary tuberculosis, but not in pulmonary Mycobacterium avium
      complex (MAC) disease. This study aimed to verify the diagnostic significance of
      gastric aspirate culture in pulmonary MAC disease. SUBJECTS AND METHODS: This
      retrospective study analyzed 77 cases of pulmonary MAC disease tentatively
      diagnosed through gastric aspirate culture in comparison with 308 cases diagnosed
      through sputum culture. RESULTS: There was no significant difference in the
      clinical symptoms, laboratory data, or type of disease in both groups. Patients
      diagnosed through gastric aspirate culture had a significantly lower chance of
      having underlying respiratory disease (26.0% vs. 46.8%), which indicates the
      difficulty in obtaining sputum specimens from this group of patients. In 114
      patients without chemotherapy intervention, more patients achieved spontaneous
      remission in the gastric aspirate group than in the sputum group. Among 271
      patients treated with chemotherapy, there were no significant differences in the
      course of radiological findings and clinical symptoms between both groups. During
      the observation period, a definitive diagnosis through sputum culture or
      histological confirmation was reached in 34 of 47 patients (72%). There was no
      significant difference in the clinical characteristics, course of radiological
      findings, and clinical symptoms in the definitive group and tentative group.
      CONCLUSION: Gastric aspirate is a minimally invasive, easy to conduct, and useful
      test for diagnosing pulmonary MAC disease.

PMID- 24908810
TI  - [Analysis on workload for hospital DOTS service].
AB  - BACKGROUND AND OBJECTIVE: A directly observed treatment short course (DOTS) trial
      was launched in Japan in the late 1990s and targeted patients with social
      depression at urban areas. Based on these findings, the Ministry of Health,
      Labour and Welfare established the Japanese DOTS Strategy in 2003, which is a
      comprehensive support service ensuring the adherence of tuberculosis patients to
      drug administration. DOTS services are initially provided at the hospital to
      patients with infectious tuberculosis who are hospitalized according to the
      Infectious Diseases Control Law. After being discharged from the hospital, the
      patients are referred to a public health center. However, a survey conducted in
      2008 indicated that all the patients do not receive appropriate DOTS services at
      some hospitals. In the present study, we aimed to evaluate the protocols and
      workload of DOTS at hospitals that are actively involved in tuberculosis medical
      practice, including DOTS, to assess whether the hospital DOTS services were
      adequate. METHOD: We reviewed a series of articles on hospital DOTS from a
      Japanese journal on nursing for tuberculosis patients and identified 25
      activities regarding the hospital DOTS service. These 25 items were then
      classified into 3 categories: health education to patients, support for
      adherence, and coordination with the health center. In total, 20 hospitals that
      had > 20 authorized tuberculosis beds were selected--while considering the
      geographical balance, schedule of this survey, etc.--from 33 hospitals where an
      ex-trainee of the tuberculosis control expert training program in the Research
      Institute of Tuberculosis (RIT) was working and 20 hospitals that had
      collaborated with our previous survey on tuberculosis medical facilities. All the
      staff associated with the DOTS service were asked to record the total working
      time as well as the time spent for each activity. The data were collected and
      analyzed at the RIT. RESULT: The working times for each activity of the DOTS
      service for nurses, pharmacists, ward clerks, head nurses, and doctors were 100,
      90, 87, 86, and 63 min, respectively. For other professions, including medical
      social workers, nursing aids, nutritionists, and physical therapists, the working
      times for each activity of the DOTS service were 31, 18, 10, and 8 min,
      respectively. The professionals who spent a longer time on health education,
      support for patient adherence, and coordination with the health center were
      pharmacists, doctors, and head nurses; nurses, pharmacists, and doctors; and head
      nurses, doctors, and ward clerks, respectively. DISCUSSION: Aging of tuberculosis
      patients was associated with problems on adherence in many patients, including
      patients who were not suited for a standard regimen, patients whose activity of
      daily life had deteriorated due to senile dementia, patients with diabetes
      mellitus, etc. Smoking cessation and mental care for cases of multi-drug
      resistant disease are new challenges in tuberculosis patient care. The present
      study clearly indicated that activities including patient education, support for
      patient adherence, and coordination with the health center--essential components
      of the hospital DOTS service according to the Japanese DOTS Strategy--were
      performed by a team of professionals including doctors, nurses, pharmacists,
      medical social workers, etc., depending on the features and roles that they serve
      and the needs of each patient. For good practice of hospital DOTS, it is
      essential to not only provide DOTS, but also effectively provide individual or
      group health education and coordinate with health centers, thus aiming towards a
      better community DOTS service after patient discharge.

PMID- 24908811
TI  - [Effectiveness of interferon-gamma release assays in the tuberculosis contact
      investigation of elderly people].
AB  - PURPOSE: To confirm the effectiveness of interferon-gamma release assays (IGRAs)
      in the tuberculosis (TB) contact investigation of elderly people, we analyzed the
      results of the QuantiFERON TB Gold in tube (QFT-3G) test, which is a commercially
      available IGRA. METHODS: We analyzed the results of the QFT-3G test in 2,420
      subjects who were in close contact with TB patients. We investigated subjects
      with latent TB infection and those showing the onset of TB among the QFT-3G
      positive subjects. RESULTS: The QFT-3G-positive rate was 7.3% (95% confidence
      interval, 6.2%-8.3%). In addition, we demonstrated that the QFT-3G-positive rate
      increased with age (P < 0.001). DISCUSSION: The QFT-3G-positive rate was high,
      particularly in elderly people (> or = 60 years), but the rate was significantly
      lower than the predicted prevalence of TB infection. Therefore, it was assumed
      that the QFT-3G test does not always provide a positive result, even in cases of
      subjects with a previous TB infection. Furthermore, data from the QFT-3G-positive
      subjects indicated that approximately one half of subjects aged 60-69 years,
      approximately one-third of those aged 70-79 years, and approximately one-quarter
      of those aged over 80 years have had recent TB infections. In conclusion, the
      results of the QFT-3G test in elderly people need to be carefully evaluated
      according to the contact situation with TB patients; nevertheless, the QFT-3G
      test is useful for the screening of latent TB infection in elderly people who
      were in close contact with TB patients.

PMID- 24908812
TI  - [Fatal nontuberculous mycobacterial lung disease caused by Mycobacterium
      kyorinense: a case report with five years of follow-up].
AB  - An 85-year-old man with dementia first visited our hospital 5 years ago,
      complaining of hemoptysis. He was hospitalized 2 years later owing to fever,
      cough, and dyspnea. A chest computed tomography scan showed infiltration with a
      cavity in the left upper lobe. He was diagnosed with nontuberculous mycobacterial
      lung infection on the basis of the presence of acid-fast bacilli in the sputum
      and repeated bronchoalveolar lavage specimens; however, we were unable to
      identify the isolate by DNA-DNA hybridization. Although his general condition had
      slightly improved after treatment initiation, intermittent chemotherapy owing to
      the adverse effects of the drugs and dementia led to rapid disease progression
      and death. After his death, the isolated mycobacterium was identified as
      Mycobacterium kyorinense by sequence analysis of the hsp 65 and rpoB genes.

PMID- 24908813
TI  - [Tuberculosis contact investigation in hospitals].
AB  - OBJECTIVE: To contribute to measures against hospital-acquired infections by
      analyzing and evaluating tuberculosis contact investigations in hospitals.
      METHODS: This study included 202 tuberculosis cases between January 2010 and
      September 2011 in which contact investigations were requested from the Public
      Health Office in Osaka City. RESULTS: 1) To assess the necessity for contact
      investigation and the demographics of index cases, contact investigations were
      conducted for 66 of the 202 cases. Index cases with higher rates of contact
      investigation included those with "higher degree of sputum smear positivity,"
      "respiratory symptoms," "period from hospitalization to tuberculosis diagnosis of
      8 days or longer," and "high-risk procedures (including endotracheal intubation,
      endotracheal aspiration, and bronchofiberscopy)." 2) A total of 632 contact
      persons from the following professions underwent QuantiFERON-TB (QFT) testing: 59
      doctors, 492 nurses, 60 other hospital staff members, and 21 patients, and the
      positive QFT rates were 18.6, 10.8, 13.3, and 14.3%, respectively. 3) Among the
      66 index cases for which contact investigations were conducted, there were 0 QFT
      positive contact persons in 37 cases (56.1%), 1 or more in 29 (43.9%), and 2 or
      more in 18 cases (27.3%). Assuming the dependent variable to be 0 and 1,
      respectively, for index cases with 0 and 2 or more QFT-positive contact persons,
      we performed a multiple logistic regression analysis with independent variables
      that included the presence or absence of high-risk procedures, period from
      hospitalization to diagnosis either within 7 days or 8 or more days, presence or
      absence of cough and cavity, and the degree of sputum smear positivity
      (1+/2+/3+). Among these variables, those significantly associated with cases with
      1 and 2 or more QFT-positive persons included the "presence of high-risk
      procedures" and "period from hospitalization to diagnosis of 8 days or longer" (P
      < 0.05). DISCUSSION: Our results suggest that early diagnosis and appropriate
      responses during high-risk procedures may be necessary measures to prevent
      hospital-acquired infections.

PMID- 24908814
TI  - [The efficacy of ethinylestradiol for castration-resistant prostate cancer].
AB  - OBJECTIVE: We analyzed the efficacy of ethinylestradiol as estrogen therapy on
      Castration-resistant Prostate Cancer (CRPC). PATIENTS AND METHODS: The study was
      conducted on 14 patients who were diagnosed as having CRPC and who were being
      prescribed ethinylestradiol (1.5-2.0 mg/day) with aspirin (100 mg/day) and an LH
      RH agonist in our hospital from August 2011. RESULTS: All patients had already
      been treated with a combined androgen blockade (CAB), 8 patients had been treated
      with docetaxel, 9 patients with tegafur-uracil, 4 patients with estramustine
      phosphate sodium. Age and prostate-specific antigen (PSA) at prescription of
      ethinylestradiol was 55-85 (median 75.5) and 0.784-508.7 ng/ml (median 4.842
      ng/ml). Thirteen patients (92.9%) achieved a decline in PSA, 8 patients (57.1%)
      achieved a decline in PSA > 50%. Time to progression was 0-18 months (median 7
      months), and there were no severe adverse events including venous thromboembolic
      diseases. CONCLUSION: Oral ethinylestradiol administration may have efficacy for
      CRPC without severe adverse events. Ethinylestradiol may be one of the selective
      drugs for CRPC patients who do not wish to undergo intravenous chemotherapy or
      become resistant to docetaxel.

PMID- 24908815
TI  - [Marked efficacy of multimodality therapy for ureteral cancer producing
      granulocyte colony-stmimulating factor].
AB  - A 69-year-old man was admitted with the chief complaint of macroscopic hematuria.
      Computerized tomography (CT) and ureteroscopy showed right ureter cancer. Right
      nephroureterectomy and partial cystectomy were performed. Histological
      examination revealed urothelial carcinoma of ureter (Grade3, pT3, INFbeta, ly1).
      The patient underwent two courses of adjuvant chemotherapy with gemcitabine and
      cisplatin. Three months later, abdominal CT showed a mass in his right
      obturatorius area. The patient's white blood cell count was 34,140 cells/microl.
      Additionally serum analysis revealed high value of granulocyte colony stimulating
      factor (G-CSF), 596 pg/ml with no obvious focus. After being diagnosed with
      recurrent ureteral cancer producing G-CSF, the patient underwent secondary
      chemotherapy with gemcitabine and docetaxel. After three courses of chemotherapy,
      CT revealed a marked decrease in tumor size, and the value of G-CSF declined at
      31 pg/nl. Subsequently, radiotherapy (60 Gy) was administered. The patient has
      been alive for 16 months.

PMID- 24908816
TI  - [Condylomatous carcinoma of the urethra that detected human papillomavirus type
      16 genome: a case report].
AB  - This is a report on a rare case of male urethral condylomatous carcinoma that
      detected human papillomavirus type 16 genome (HPV16). He had been administered
      immunosuppressant, since he had a kidney transplant in 1977. Papillary tumors
      spread from the external urethral opening to the membranous urethra.
      Histologically, the tumors presented papillary growth and koilocytotic atypia on
      the surface part. Moreover, we observed corpus spongiosum penis invasion and vein
      invasion, and detected HPV16 by immunostaining. We diagnosed condylomatous
      carcinoma. We treated with anterior urethrectomy and cystostomy.

PMID- 24908817
TI  - [IgG4-related kidney disease: a long-term follow up case of pseudotumor of the
      renal pelvis].
AB  - A 69-year-old man had undergone left ureteronephrectomy because of a left renal
      pelvic tumor, however the pathological diagnosis was inflammatory pseudotumor.
      About 1 year later, computed tomography showed a mass at the right kidney near
      the hilar. Ureterorenoscopy and urine cytology were performed, and their results
      showed no evidence of malignancy. He had been followed closely without therapy.
      The mass increased in size during follow-up, and we reviewed the surgical
      specimen of the left ureteronephrectomy. Immunohistochemical studies revealed
      diffuse infiltration by IgG4 positive plasma cell. His serum IgG4 was high. We
      diagnosed him as IgG4-related kidney disease. In response to treatment with
      corticosteroid, the size of the tumor and serum IgG4 levels decreased. Most
      reported cases of IgG4-related disease involving kidney have a history of prior
      pancreatic involvement. We report a rare long term follow-up case of IgG4-related
      kidney disease without pancreatic involvement.

PMID- 24908818
TI  - [Three cases of IgG4-related focal retroperitoneal fibrosis].
AB  - (Case 1) A 63-year-old man was diagnosed as retroperitoneal fibrosis by the
      exploratory laparotomy for the pelvic mass with high IgG4 levels. (Case 2) A 64
      year-old man had past medical history of autoimmune pancreatitis which was
      treated by steroid use. Three years later, he was diagnosed as IgG4-related
      gallbladder tumor by the cholecystectomy. And, then he was diagnosed as right
      hydronephrosis with high IgG4 levels. (Case 3) A 71-year-old man was diagnosed as
      left hydronephrosis and pelvic mass by computerized tomography with high IgG4
      levels. We reported three cases of IgG4-related focal retroperitoneal fibrosis.
      All cases had pelvic mass with high IgG4 levels and were also treated effectively
      with steroid use. Those symptoms of the patients occurred in close association
      with IgG4 levels. It is necessary to acknowledge that retroperitoneal fibrosis
      may have aspects of IgG4-related systemic disease and that the measurement of
      serum IgG4 should be considered for diagnosing and treating the conditions.

PMID- 24908820
TI  - Guys, we need you down here.

PMID- 24908819
TI  - [The Japanese version of the National Institutes of Health Chronic Prostatitis
      Symptom Index].
AB  - The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) is
      the standard questionnaire that determines the degree of symptoms and efficacy of
      treatment in patients with chronic prostatitis/chronic pelvic pain syndrome.
      Because there was no officially approved Japanese version of the NIH-CPSI, the
      Japanese Urological Association (JUA) formed a committee to develop one chaired
      by Dr. Masayuki Takeda, who also chairs the special field of voiding function and
      neurourology in the JUA. Consequently, the committee produced a Japanese version,
      referring to previous proposals and the Japanese version of the International
      Prostate Symptom Score. The committee strongly expects that the Japanese version
      of the NIH-CPSI will be taken full advantage of in future clinical research.

PMID- 24908822
TI  - Emergency planning in kidney care--it's everyone's responsibility.

PMID- 24908821
TI  - Advanced practitioners are nephrology's future.

PMID- 24908823
TI  - New alternatives in anemia treatment: biosimilars and HIF stabilizers.

PMID- 24908824
TI  - Nephrology social work: a primer.

PMID- 24908825
TI  - Case management and the new nephrology social worker.
AB  - Case management is thought to be an effective way to offer counseling services
      and integrate the coordination of other services 4 into an efficient care
      delivery model. Through communication, collaboration and outcome-driven
      interventions, nephrology social workers can make a difference in health risk
      behaviors through case management.

PMID- 24908826
TI  - How to demonstrate that nephrology social work is effective.

PMID- 24908827
TI  - STI: one treatment approach.

PMID- 24908828
TI  - Role of the social worker and the transplant center QAPI committee.
AB  - Transplant social workers are actively involved with transplant center QAPI,
      evaluating the psychosocial factors involved in-patient and living donor
      candidacy, selection, and short and long term outcomes. This involves working
      closely with the other mental health and medical members of the transplant team
      and QAPI committee. It is important for transplant centers to incorporate
      psychosocial factors into evaluation of transplant patient and graft survival
      outcomes.

PMID- 24908829
TI  - Resources.

PMID- 24908830
TI  - The new ESRD core survey: Part 2: strategy important in developing an action
      plan.
AB  - My experience with facilities that have been through a Core Survey is that if an
      issue or concern arises during a survey, the surveyor will ask to see the QAPI
      meeting minutes. If in the QAPI minutes, the interdisciplinary team has
      identified the concern, developed an action plan, and is working toward a remedy
      for that concern, the concern may not be cited as a deficient practice.
      Identifying your own problems is better than a "get out of jail free" card,
      because it allows you to proactively take actions and keep patients safe. The
      Core Survey process supports collaboration with CMS in identifying our own areas
      of concern and working toward safe and quality solutions. I am optimistic about
      the future of dialysis and the delivery of care. One way to embrace these
      concepts is to sit down at the chair side and ask each patient, "How can we do
      better?" Listening, and taking action will drive care forward by using a
      strategic and collaborative approach.

PMID- 24908831
TI  - Leading from the front.

PMID- 24908832
TI  - The challenge of creating a 'we're all this together' culture in Addenbrooke's
      theatres.
AB  - In the wake of seven consecutive never events in theatres during 2011-2012,
      senior managers at Addenbrooke's had a challenge--to raise morale and support
      staff to fully support the WHO surgical safety checklist process. Theatres
      operations manager Maggie Ward and the theatres team took some innovative steps
      to change culture in theatres.

PMID- 24908833
TI  - Anaesthetic nurse specialist role: leading and facilitation in clinical practice.
AB  - Leadership and its effectiveness is becoming more prevalent within the nursing
      profession with anaesthetic nurse specialists showing their ability to lead,
      inspire and motivate others to work towards a shared vision in the rapidly
      changing peri-anaesthesia environment. Anaesthetic nurse specialists must
      therefore be aware of their personal leadership skills and continually develop
      these within clinical practice. They are also well placed regarding the
      facilitation of learning.

PMID- 24908834
TI  - Surgical swab counting: a qualitative analysis from the perspective of the scrub
      nurse.
AB  - The aim of the study was to conduct a qualitative exploration of the
      sociotechnical processes underlying retained surgical swabs, and to explore the
      fundamental reasons why the swab count procedure and related protocols fail in
      practice. Data was collected through a set of 27 semistructured qualitative
      interviews with scrub nurses from a large, multi-site teaching hospital.
      Interview transcripts were analysed using established constant comparative
      methods, moving between inductive and deductive reasoning. Key findings were
      associated with interprofessional perspectives, team processes and climate and
      responsibility for the swab count. The analysis of risk factors revealed that
      perceived social and interprofessional issues played a significant role in the
      reliability of measures to prevent retained swabs. This work highlights the
      human, psychological and organisational factors that impact upon the reliability
      of the process and gives rise to recommendations to address contextual factors
      and improve perioperative practice and training.

PMID- 24908835
TI  - Safety in the emergency situation: the airway--a theatre team approach.
AB  - Managing an expected or unanticipated difficult airway can result in morbidity
      and even mortality (Cook et al 2011). These scenarios place considerable demands
      on the anaesthetic team and require the wider support of theatre staff. It is
      crucial that the perioperative team is adequately prepared for these time
      critical emergencies in order to prevent avoidable patient harm. This article
      introduces the topic and discusses the core knowledge and skills required of the
      perioperative team.

PMID- 24908836
TI  - Safeguarding adults.
AB  - The safeguarding of patients is a key concern for all health and care
      professionals. Research shows that more instances of unacceptable care are likely
      to occur due to an increase in population of those deemed to be vulnerable.
      Increasing professionals' awareness, knowledge and understanding of safeguarding
      and of the systems in place for reporting concerns is essential for best practice
      and for protecting patients and their families.

PMID- 24908837
TI  - [The elderly and new technologies].

PMID- 24908838
TI  - [Loneliness and cognitive decline].

PMID- 24908839
TI  - [Parkinson disease and the risk of falls].

PMID- 24908840
TI  - [Suicide crisis, psychological suffering and advanced age].
AB  - Bound to the idea of a crisis and the brutal intrusion of psychological
      suffering, the suicide drama rarely lends itself to a direct analysis which can
      highlight the different stages of its process. Taking into account increasing
      quantities of scientific data from current research and the spirit of crisis
      interventions is fundamental for allowing hopes of effective prevention. Speaking
      the same language by using the same conceptual basis, that of the suicide crisis,
      is a prerequisite in pedagogical terms for the current care management of
      suicidal patients.

PMID- 24908841
TI  - [Music therapy and Alzheimer disease].
AB  - Music therapy and Alzheimer's dementia. Dementia such as Alzheimer's leads to the
      deterioration of the patient's global capacities. The cognitive disorders
      associated with it are disabling and affect every area of the patient's life.
      Every therapy's session undertaken with and by patients can act as a mirror of
      the progress of their disease and help to feel better, as described in this
      article on music therapy.

PMID- 24908842
TI  - [Interdisciplinary collaboration in services for the elderly].

PMID- 24908843
TI  - [New forms of health care coordination in geriatrics].
AB  - The global care of elderly patients leads to new forms of coordination between
      allied healthcare professionals. They are based on completely new ethical issues
      relating to the responsibility of all the healthcare professionals involved.
      These new practices call for the mobilisation of new skills, the development of
      new teaching and research into interprofessional collaboration.

PMID- 24908844
TI  - [Working together in gerontology].
AB  - The complexity of care situations notablywith regard to the care of frail
      dependent elderly people suffering from chronic pathologies, requires a specific
      approach, a partnership between a nurse and nursing auxiliary and inter
      disciplinarity. This work organisation positions the elderly person at the centre
      of the approach to ensure they are considered as a partner in the care. Improving
      exchanges and constructing a common understanding are real necessities for
      professionals working in gerontology.

PMID- 24908845
TI  - [The development and benefits of working together in geriatric short stay units].
AB  - Ambroise-Pare hospital (AP-HP, 92) set up a new work organisation based on the
      nurse/nursing auxiliary partnership in the geriatric short stay unit in response
      to the wishes of the healthcare manager and nursing team. It was introduced over
      three months and in several stages in order to limit sticking points and support
      the team in its new practice.

PMID- 24908846
TI  - [Coordination in hospital-based home care].
AB  - Hospital at home involves multidisciplinary teams who provide care 24/7 in the
      homes of increasingly elderly patients. They present complex medical, mental and
      social needs with secondary functional incapacities.

PMID- 24908847
TI  - [Oral communication between colleagues in geriatric care units].
AB  - Transmitting information orally between colleagues in gerontology care units.
      While the only certified method of transmitting nursing information is in
      writing, the oral tradition remains firmly rooted in the practice of health care
      providers. Professionals caring for elderly patients need to exchange information
      -whether it be considered important or trivial-, anywhere and at any time. In
      this article, professionals describe how they were able to identify which
      configurations of players and teams enable information to flow and benefit the
      care of elderly patients.

PMID- 24908848
TI  - [Nurse and nurses' aides collaboration in nursing homes].

PMID- 24908850
TI  - [Bibliography. Interdisciplinary cooperation].

PMID- 24908849
TI  - [Improving communication with the general practitioner].
AB  - Private practice nurses, in partnership with the general practitioner, provide
      the majority of home care and primary care of elderly people. They are therefore
      best placed to prevent and detect decompensation risk factors in their frail
      elderly patients. A pilot study aims to assess the impact of a tool on the
      quality of transmission of information with the general practitioner and of the
      global care management.

PMID- 24908851
TI  - [Do not neglect the care of the primary caregiver].

PMID- 24908852
TI  - [Medication risk management].

PMID- 24908853
TI  - Practicing medicine thirty years on.

PMID- 24908854
TI  - Retrospective costing of warfarin.
AB  - In Ireland, there are four anticoagulants available for prescribing to patients
      with atrial fibrillation for stroke prevention. A key feature of the three most
      recent anticoagulants is that monitoring is redundant. Despite this, there is
      continued prescribing of the incumbent anticoagulant, warfarin, which requires
      monitoring. Lack of information regarding the cost of monitoring, and the extra
      burden it places on health budgets and patients, motivated this costing study.
      Using micro costing, the costs of warfarin treatment (including monitoring) was
      disaggregated and isolated from both the patients' and health care provider's
      perspectives in a Cork hospital. Costs to the health care provider per patient
      per clinic visited were 21.57 Euros. Patient costs incurred per patient per
      clinic were 48.50 Euros. Thus, the total costs per patient per visit were 70.07
      Euros. This result reveals that while the pharmaceutical cost of warfarin is low;
      it is not an inexpensive therapy when monitoring costs are considered.

PMID- 24908855
TI  - Introduction of oesophageal Doppler-guided fluid management in a laparoscopic
      colorectal surgery enhanced recovery programme: an audit of effect on patient
      outcome.
AB  - Morbidity after colorectal surgery can be reduced with intraoperative oesophageal
      Doppler monitor (ODM) guided fluid therapy. We audited the effect of introducing
      ODM-guided fluid therapy in enhanced recovery laparoscopic colorectal surgery.
      ODM group (n = 40) outcomes (toleration of diet, Post Operative Morbidity Survery
      (POMS) score, complications) were compared to matched patients (n = 40) who had
      the same surgery using a conventional approach to fluid management. Mean (SD)
      time to tolerate diet was shorter in the ODM group (2.3 (1.6) days vs 3.8 (2.4)
      days, p = 0.003). The ODM group had a lower mean (SD) POMS score on post
      operative day 1 (2 (1.4) vs 4 (1.1), p = 0.001), fewer postoperative
      complications (14 patients vs 20, p = 0.009) and a lower rate of unplanned
      critical care area admission (1 vs 6, p= 0.001). Introduction of intraoperative
      ODM-guided stroke volume optimization was associated with improved outcomes in
      patients undergoing enhanced recovery laparoscopic colorectal surgery.

PMID- 24908856
TI  - Are we ready to "think ahead"? Acceptability study using an innovative end of
      life planning tool.
AB  - This is a cross sectional study in 5 GP Training Practices, sample size 100
      clinically stable patients, attending for routine care. Purpose of the study was
      explained and informed written consent was sought. Participants were provided
      with 'Think Ahead,' an innovative end of life planning tool, devised by The Forum
      on The End of Life, based on best international practice, presented in a
      questionnaire format, detailing main decision centres relevant in end of life
      planning. Participants completed telephone surveys at 1 and 3 weeks, ascertaining
      their experience with 'Think Ahead;' 92/100 completed both surveys. Results
      indicate high levels of acceptability and positive experience for most
      participants. A majority (63%) indicated 'no difficulty' in completing 'Think
      Ahead;' 74% indicated reported they did not find completing the folder to cause
      upset; 87% indicated they felt the folder should be more widely available, and
      68% indicated they felt 'Think Ahead' would be of general interest. The study was
      effective in encouraging discussion on end of life issues with family (83%) with
      49% indicating they had done so in detail, and 34% indicating having 'done so
      somewhat,' having read 'Think Ahead; 27% indicated aspects of it were upsetting.
      Results will be used to inform further development of the tool. General Practice
      consulting is a suitable context in which to systematically present 'Think
      Ahead.'

PMID- 24908857
TI  - Management of parenteral nutrition associated hyperglycaemia: a comparison of
      subcutaneous and intravenous insulin regimen.
AB  - PN is associated with significant hyperglycaemia, which may be detrimental to
      clinical outcome. There are few data on the management of this phenomenon outside
      of intensive care units. In our unit, we studied the efficacy of protocol-based
      intravenous insulin delivery as compared to subcutaneous insulin prescribed
      individually outside of the critical care setting. In a retrospective review over
      a two-year period, we compared patients with PN-associated hyperglycaemia who had
      received both modes of insulin therapy. A total of 122 who developed PN
      associated hyperglycaemia were identified. Those on the intravenous insulin
      regimen were within glycaemic target for more time than those on the subcutaneous
      regimen (62% Vs 43%, p = 0.008). We therefore conclude that outside of the
      critical care setting, intravenous insulin delivers better glycaemic control and
      should therefore be considered optimum therapy for patients with PN-associated
      hyperglycaemia.

PMID- 24908858
TI  - Delays in the stroke thrombolysis pathway--identifying areas for improvement.
AB  - Despite international consensus on the benefits of thrombolysis for ischaemic
      stroke (IS), it remains underused. Guidelines now recommend a door-to-needle time
      of 60 minutes. We reviewed the rate and timeliness of thrombolysis for IS at our
      hospital. 323 stroke patients presented between January 2011 and April
      2012.Thirty patients (10.6% of IS) were thrombolysed, mean age was 68.5 years (42
      to 88) and 19 patients (63%) were male. Thirty-six patients (12.7% of IS) were
      not thrombolysed despite arriving within the time-window and symptom resolution
      was the commonest reason (15 patients; 42%). Despite most thrombolysed patients
      (42%) presenting to the Emergency Department during daytime working hours, there
      were delays at each step of the acute care pathway. The mean time for stroke team
      review was 23 minutes (5-50). The mean door-to-CT and the door-to-needle times
      were 60 minutes (25-95) and 92 minutes (46-130) respectively. In parallel with
      national stroke incentives, local audit can highlight barriers to uptake and
      efficiency within thrombolysis services.

PMID- 24908859
TI  - Managing newborn ileostomies.
AB  - The early post-ileostomy medical management of neonates is not clearly defined. A
      retrospective chart review of all infants who received an ileostomy March 2010
      December 2011, identified the post-operative ileostomy progress of each infant.
      There were 16 cases of neonatal ileostomy during the study period. Over the first
      14 postoperative days there was no weight gain. By 21 days the infants were
      gaining a median 140 g/week. The median stoma output was 5 mls/kg/dy during the
      first 7 days increasing to 17.5-20 mIs/kg/dy. Weight gain or weight loss was
      closely related to the consistency and volume of the stoma output. Ten infants
      had a hig stoma output > 20 mls/kg/dy (3 preterm, 7 term). This high stoma output
      was associated with sub-optimal weight gain. This study provides a template for
      the expectant management of newborn infants after an ileostomy. The critical
      issues are weight gain, stoma output and local and systemic complications.

PMID- 24908860
TI  - Congenital-infantile fibrosarcoma of the foot--avoidance of amputation.
AB  - Congenital-infantile fibrosarcoma is a rare entity with a five year survival rate
      of over 90%. Surgery is still the most common treatment modality with amputation
      often necessary. There have been reports supporting the use of neoadjuvant
      chemotherapy to debulk the tumour in an effort to facilitate limb sparing
      surgery. We report a case of a newborn who presented with a life threatening
      haemorrhage from a fibrosarcoma of the foot, successfully treated with
      Vincristine, Actinomycin and Cyclophosphamide (VAC) chemotherapy alone.

PMID- 24908861
TI  - Gastrointestinal Erdheim-Chester disease.
AB  - We report a rare case of Erdheim-Chester Disease, a non-Langerhans cell
      histiocytosis. A 60-year old female presented with a seven-month history of vague
      abdominal symptoms. A large retroperitoneal mass was detected on computed
      tomography (CT), but multiple CT-guided biopsy samples were inconclusive.
      Laparoscopy revealed a mass in the distal ileum, which was resected. Histology
      and immuno-histochemistry supported a diagnosis of Erdheim-Chester Disease.

PMID- 24908862
TI  - Infants with FPIES to solid food proteins--chicken, rice and oats.
AB  - We present two cases of Food Protein Induced Enterocolitis Syndrome (FPIES), a
      non-IgE mediated food hypersensitivity. FPIES induces severe vomiting 1.5-to-3
      hours post ingestion of the offending food, and may be associated with diarrhoea,
      hypovolemic shock and acidosis. Avoidance of that food will lead to resolution of
      symptoms and prevents further episodes.

PMID- 24908863
TI  - Triad of emboli in acute flare of ulcerative colitis.
AB  - Arterial thrombosis is rare in ulcerative colitis (UC). Our case report described
      a triad of arterial emboli in a UC patient who presented with bilateral lower
      limb claudication associated acute chest pain, confusion, ataxia and diplopia.
      Investigations confirmed bilateral femoral and popliteal artery occlusion,
      occipital infarct and a sub-endocardial infarct secondary to embolic disease.

PMID- 24908864
TI  - Beware: unilateral Reinke's oedema of the larynx.
AB  - A thirty year-old man presented with hoarseness of recent onset. The underlying
      cause was a glottic schwannoma, which led to development of unilateral Reinke's
      oedema. Schwannomas arising in the paraglottic space are rare.

PMID- 24908865
TI  - Difficulties associated with diabetes management during the Junior Certificate
      examination.
AB  - The aim of this study was to describe the adherence to recommended diabetes care
      during the Junior Certificate, and the utilisation of available allowances for
      children with type 1 diabetes. Questionnaires were sent within 3 months of the
      examination to all adolescents and their families attending our service
      completing the Junior Certificate in June of 2012. Fifteen of the 25 (60%)
      patients/parents completed the questionnaires. Five (33%) had higher than usual
      glucose readings during the examination period and three (20%) experienced
      hypoglycaemia during at least one exam. Nine (60%) never checked capillary
      glucose levels during the exams. No patients left the examination area to perform
      diabetes related tasks. Thirteen (86%) brought fast acting glucose into the
      examination centre while only six (40%) brought a glucometer. Just four (27%)
      patients availed of the rest breaks allowed and six (40%) felt that their
      diabetes affected their examination performance.

PMID- 24908866
TI  - An example of ideal utilisation of specialist services by primary care: cervical
      check.
AB  - Cancer of the cervix is the 8th most common cancer for women in Ireland.Cervical
      Check has organised and combated this clinical presentation nationwide and has
      shown encouraging figures since its launch in 2007. While working in Kerry
      General Hospital (KGH), the Southwest Specialist Training Scheme in General
      Practice carried out an audit of the colposcopy referrals being received from GPs
      in the southwest. Adherence to Cervical Check referral guidelines was the main
      focus of the audit. Very positive figures presented in round one of the audit
      cycle, with 51 (90%) of all GP referrals adhering to the guidelines. This was
      further improved by a GP information campaign, leading to 57 (93%) of referrals
      meeting the appropriate referral criteria. Overall, this paper highlights the
      excellent screening programme that is Cervical Check and the superb working
      relationship between primary and secondary care facilities.

PMID- 24908867
TI  - [Cholecystolithiasis in his history. Elderly man with acute abdomen. Gallstone
      ileus].

PMID- 24908868
TI  - ["Relaxation trip" with remarkable effects. Hypnosis for cancer patients
      (interview by Dr. Beate Schumacher)].

PMID- 24908869
TI  - [General practice report. Power management for diabetic patients].

PMID- 24908870
TI  - [How long are waiting times in the Hamburg practice? (interview by Dirk
      Schnack)].

PMID- 24908871
TI  - [Ensuring medical care. MVZ (medical care centers) are on the average of only
      limited use].

PMID- 24908872
TI  - [Medication control monitoring in amiodarone therapy. What is essential?].

PMID- 24908873
TI  - [Health counseling online. The internet as a source of confusion].

PMID- 24908874
TI  - [Fine particle dust. Killer particles - more dangerous than malaria].

PMID- 24908875
TI  - [Chronic urticaria. of hives - how to treat? Hives again and again - how to
      treat?].

PMID- 24908876
TI  - [French study: a fat joint is a friend of the heart attack].

PMID- 24908877
TI  - [Palpitations, tachycardia and dyspnea. Myocarditis - what else?].

PMID- 24908878
TI  - [Regardless if it's liquor, wine or beer - all alcoholic beverages induce gout
      attacks].

PMID- 24908879
TI  - [Risk of type 2 diabetes with early menarche].

PMID- 24908880
TI  - [The most thorough assessment to date of homeopathy].

PMID- 24908881
TI  - [Early thrombolysis in stroke: every minute saves a day].

PMID- 24908882
TI  - [Irritable bowel syndrome - diet modifies the symptoms].

PMID- 24908883
TI  - [Genetic technique stops degeneration of mouse muscles].

PMID- 24908884
TI  - [Cardiovascular risk is elevated in overweight pregnant patients].

PMID- 24908885
TI  - [A new score for intracranial aneurysms].

PMID- 24908886
TI  - [Diabetology for the general practitioner: common questions and the answers of
      the experts].

PMID- 24908887
TI  - [Is there a rationale for early insulin treatment in type 2 diabetes?].

PMID- 24908888
TI  - [The diabetic patient with nephropathy].

PMID- 24908889
TI  - [Sexuality and incontinence].

PMID- 24908890
TI  - [Outpatient anticoagulation].

PMID- 24908891
TI  - [Surgery in the elderly--indications and risks assessment].

PMID- 24908892
TI  - [Caffeine in analgesics--myth or medicine?].

PMID- 24908893
TI  - [Adiposity paradox in cardiovascular disease].

PMID- 24908894
TI  - [Individualized medicine. DNA tests for better treatment safety].

PMID- 24908895
TI  - [Flupirtine. Therapy of episodic tension headache].

PMID- 24908896
TI  - Burning issue. 1964.

PMID- 24908897
TI  - Bugs, drugs, hospitalists, and a new chapter.

PMID- 24908898
TI  - A social-ecologic framework for improving bicycle helmet use by children.

PMID- 24908899
TI  - Management of neutropenic fever during a transition from traditional
      hematology/oncology service to hospitalist care.
AB  - OBJECTIVES: Increasingly, hospitalists across the United States provide primary
      inpatient care for almost all subspecialty patients, including hematology and
      medical oncology. Febrile neutropenia (FN) is a serious condition often seen as a
      complication of cytotoxic chemotherapy or in patients with underlying bone marrow
      defects. The purpose of this study was to document the change of inpatient
      management of a common admission diagnosis during a transition of providers from
      hematologists/oncologists to the use of hospitalists in a tertiary care medical
      center, and to compare the appropriateness of treatment and outcomes over a
      period of 5.5 years of this transition. METHODS: The medical records of all
      patients with neutropenia at a community-based teaching hospital during a period
      of conversion from hematologist/oncologist to hospitalist coverage were
      retrospectively reviewed. Patients with fever and absolute neutrophil counts of
      less than 500/ microL (.5 x 10(9)/L) on admission were included. Study cases were
      divided into 3 groups by admission date, roughly demarcating the nascent
      hospitalist era, the era of transition to hospitalist, and the mature hospitalist
      era. Management of FN during these eras was compared. RESULTS: Three hundred
      ninety-nine inpatients were identified as neutropenic. Of these, 184 did not meet
      case-inclusion criteria. The remaining 215 cases were included in the study. The
      internal medicine hospitalist service admitted less than 10% of this population
      in 2003, but by 2007-2008 it admitted over 90%. The use of 4th-generation
      cephalosporins and carbapenems increased over time (P = .027), and the infectious
      disease service was consulted more frequently over time (P = .007). Outcomes
      varied due to changes in underlying disease states, use of hospice services, and
      changes in the types of patients hospitalized with FN. Morbidity decreased due to
      the change in the type and nonantibiotic therapy of cases, but inappropriate
      antimicrobial treatment was unusual, and septic morbidity or mortality related to
      inappropriate therapy was too rare to compare through these eras. CONCLUSION:
      Over the 3 eras compared, care of most neutropenic fever patients was transferred
      from specialists to hospitalists. Care became more uniform, guideline based, and
      used more infectious disease consultation, and mortality decreased. Complex
      changes in the types and treatments of cancer, neutropenia therapy, and in the
      types of patients hospitalized with FN prevent any conclusion of added value for
      this change in the type of primary provider management.

PMID- 24908900
TI  - An investigation of antibiotic susceptibility to empiric therapy for community
      associated methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: To analyze antibiotic susceptibility patterns of community-associated
      methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from skin
      and soft tissue infections among Wisconsin outpatients. DESIGN: Retrospective
      genotype testing. SETTING: Isolates were forwarded to the Wisconsin State
      Laboratory of Hygiene and Marshfield Labs from clinical laboratories throughout
      Wisconsin. METHODS: MRSA isolates submitted during April, 2010-February, 2012
      underwent genotype analysis using pulsed-field gel electrophoresis. Antibiotic
      susceptibility patterns were determined for all isolates identified by
      electrophoresis subtyping as strain type USA300, and pattern comparisons were
      made by public health region. RESULTS: Among 835 MRSA isolates submitted, 217
      (26%) were genotyped. Of these, 152 (70%) were USA300 MRSA. Among the 152 USA300
      isolates, 95% were susceptible to clindamycin and 99% were susceptible to
      tetracycline and trimethoprim-sulfamethoxazole. The proportion of clindamycin
      susceptible isolates from the southern region was significantly lower when
      compared to the other 4 regions combined (P = 0.03). One southern region
      clindamycin-resistant isolate was also resistant to trimethoprim
      sulfamethoxazole. CONCLUSIONS: USA300 MRSA was the predominant strain isolated
      from outpatient skin and soft tissue sites. Antibiotic susceptibility patterns
      among Wisconsin USA300 MRSA isolates are similar to patterns found in national
      studies. Local providers should continue to follow national practice guidelines
      for treatment of outpatient skin infections. A cluster of 4 clindamycin-resistant
      isolates and 1 trimethoprim-sulfamethoxazole resistant isolate was detected in
      the southern region, warranting continued surveillance for antibiotic resistance
      among community-associated MRSA isolates.

PMID- 24908901
TI  - A pilot study of herbal medicine use in a Midwest Latino population.
AB  - BACKGROUND: Herbal medicine use is common in the United States, especially in
      immigrant populations. Understanding of this plant use is incomplete, with
      significant gaps in the literature for people living in the Midwest, about the
      plant species used, and about how home herbal medicine use interacts with
      allopathic medicine. METHODS: This pilot project used a qualitative research
      approach (interviews and focus groups, convenience sampling) to explore this
      topic for Latin America immigrants living in Madison, Wisconsin. RESULTS: Eight
      interviews and focus groups consisting of 42 people yielded 199 minutes of audio
      recordings and the mention of 57 medicinal plants. These plants were obtained
      from gardens, relatives and friends (abroad and local), mail order, and local
      retail establishments. Retail sites sold fresh plants, dried plants, spices,
      foods, and packaged products, ranging from 20 to over 150 plant products per
      site. A preponderance of plants, especially in Latino-focused stores, was food
      that also served a medicinal purpose. Participants mentioned 35 distinct health
      and disease categories for which herbal medicines were used, and sometimes, but
      not always, discussed plant use with their health care provider. When compared
      with likely Latin binomial taxonomic names, clinically relevant confusions with
      the use of common plant names also were identified. DISCUSSION: Overall, the
      findings presented illustrate the complexities surrounding herbal medicine use
      and create a case for future work to involve other demographics, and focus on
      botanical identification, the quantification of disclosure rates, and the
      development of educational interventions for physicians and patients.

PMID- 24908902
TI  - A case of late-onset segmental neurofibromatosis.
AB  - Segmental neurofibromatosis (NF5) is a rare variant of neurofibromatosis. To our
      knowledge, there have been few reports of cases presenting later in life. The
      recognition of NF5 is important, as there have been reports of paraneoplastic
      manifestations and transmission to offspring. Here we present the case of a
      patient who presented with NF5 first appearing in her mid-50s. This case
      illustrates the subtle nature of NF5, which often leads to misdiagnosis.

PMID- 24908904
TI  - The 50th anniversary of the Surgeon General's Report on Smoking and Health:
      reflections and lessons to be learned for other public health challenges.

PMID- 24908903
TI  - Neurocysticercosis in Wisconsin: 3 cases and a review of the literature.
AB  - Neurocysticercosis is the most common parasitic infection of the brain. Endemic
      in many regions of the world, neurocysticercosis is now showing up in nonendemic
      areas such as Wisconsin. We present 3 patients that illustrate features typical
      for neurocysticercosis in anon-endemic area, including immigrant/travel status,
      presentation with focal seizures, classic magnetic resonance imaging features of
      single enhancing lesions, and good response to treatment with anticonvulsants,
      anti-inflammatory agents, and cysticidal drugs. It behooves physicians involved
      in the care of at-risk populations to be aware of the clinical features,
      radiographic signs, diagnostic tests, and general principles for treating
      neurocysticercosis.

PMID- 24908905
TI  - External peer review services available through MetaStar.

PMID- 24908906
TI  - [Oxidative and nitrative DNA damage induced by environmental factors and cancer
      risk assessment].

PMID- 24908907
TI  - [Probiotic nutrition therapy for nonalcoholic fatty liver disease].

PMID- 24908908
TI  - Miso (Japanese soybean paste) soup attenuates salt-induced sympathoexcitation and
      left ventricular dysfunction in mice with chronic pressure overload.
AB  - The hypothalamic mineralocorticoid receptor (MR)-angiotensin II type 1 receptor
      (AT1R) pathway is activated in mice with chronic pressure overload (CPO). When
      this activation is combined with high salt intake, it leads to
      sympathoexcitation, hypertension, and left ventricular (LV) dysfunction. Salt
      intake is thus an important factor that contributes to heart failure. Miso, a
      traditional Japanese food made from fermented soybeans, rice, wheat, or oats, can
      attenuate salt-induced hypertension in rats. However, its effects on CPO mice
      with salt-induced sympathoexcitation and LV dysfunction are unclear. Here, we
      investigated whether miso has protective effects in these mice. We also evaluated
      mechanisms associated with the hypothalamic MR-AT1R pathway. Aortic banding was
      used to produce CPO, and a sham operation was performed for controls. At 2 weeks
      after surgery, the mice were given water containing high NaCl levels (0.5%, 1.0%,
      and 1.5%) for 4 weeks. The high salt loading in CPO mice increased excretion of
      urinary norepinephrine (uNE), a marker of sympathetic activity, in an NaCl
      concentration-dependent manner; however, this was not observed in Sham mice.
      Subsequently, CPO mice were administered 1.0% NaCl water (CPO-H) or miso soup
      (1.0% NaCl equivalent, CPO-miso). The expression of hypothalamic MR, serum
      glucocorticoid-induced kinase-1 (SGK-1), and AT1R was higher in the CPO-H mice
      than in the Sham mice; however, the expression of these proteins was attenuated
      in the CPO-miso group. Although the CPO-miso mice had higher sodium intake, salt
      induced sympathoexcitation was lower in these mice than in the CPO-H group. Our
      findings indicate that regular intake of miso soup attenuates salt-induced
      sympathoexcitation in CPO mice via inhibition of the hypothalamic MR-AT1R
      pathway.

PMID- 24908909
TI  - It's what physicians do year after year.

PMID- 24908910
TI  - "Moving and losing": A pilot study incorporating physical activity to decrease
      obesity in the pediatric population.
AB  - OBJECTIVE: This study was developed as a pilot study to determine if targeted
      interventions regarding increasing physical activity level through the use of
      pedometers and fitness DVDs would result in a decrease in BMI in overweight or
      obese children. METHODS: 24 children aged 4-17 taking part in "Moving and Losing"
      were randomized to (1) Control Group; (2) Pedometer Group; (3) DVD Group; (4)
      Pedometer + DVD Group and asked to complete self-report physical activity logs at
      visit one and two. Baseline, midpoint, and endpoint weight, height, Body Mass
      Index (BMI) were measured for outcome variables. RESULTS: Almost half (42%) of
      participants turned in their activity logs and pedometers at midpoint, but at
      endpoint less than a quarter of participants turned in their pedometers and/or
      activity logs. BMI increased by 4.1% in the Control Group, 8.7% in the Pedometer
      Group, and 6.7% in the DVD Group. BMI decreased by 0.3% in the Pedometer + DVD
      Group. CONCLUSION: The use of pedometers and fitness DVDs may not be culturally
      acceptable in African-American female children and adolescents from South
      Carolina who are overweight or obese. Further studies should look into in-depth
      needs assessments and planning processes that include participants as
      stakeholders.

PMID- 24908911
TI  - Transcatheter aortic valve replacement--the initial MUSC experience.

PMID- 24908912
TI  - Assessing adherence to American Diabetes Association recommendations for
      hemoglobin A1C goals.

PMID- 24908913
TI  - Private practice and academia--six degrees of separation.

PMID- 24908914
TI  - The prevention of cervical cancer in developing nations.

PMID- 24908915
TI  - A new insight into retinal vein occlusion pathogenesis.
AB  - AIM: To evaluate (ex vivo) the characteristic of fibrin clotting in patients with
      retinal vein occlusion. MATERIAL AND METHODS: Fifty nine patients with a history
      of retinal vein occlusion were enrolled in the study. The diagnosis of retinal
      vein occlusion was based on the typical fundus appearance, supplemented by
      digital photography, fluorescein angiography, and optical coherence tomography.
      The control group consisted of 59 subjects matched for age, sex, body mass index,
      medications, and cardiovascular risk factors. The ex vivo fibrin clots obtained
      from citrate plasma samples from all patients were used for the measurement of
      clot permeation, expressed as the permeability coefficient, Ks (Darcy constant).
      The turbidity of fibrin clot formation, reflected by the "lag phase" of the
      turbidity curve and maximum absorbance at plateau (deltaAb(max)), tissue
      plasminogen activator (t-PA) - induced fibrinolysis characterized by maximum
      rates of increase in D-dimer levels (D-Drate) and maximum D-dimer concentrations
      (D-Dmax) were evaluated. The time required for 50% decrease in maximum clot
      absorption (t50%) was chosen as an additional marker of clot susceptibility to
      fibrinolysis. RESULTS: Patients with retinal vein occlusion were characterized by
      the unfavourable plasma fibrin clot properties. Clot permeability was 30% lower,
      as compared to the controls (p < 0.0001), the "lag phase" was 11% shorter (p <
      0.0001) indicating faster fibrin formation, and the deltaAb(max) was 19% higher
      (p < 0.0001), indicating thicker fibrin fibers. The D-Dmax indicating thrombotic
      mass available for fibrinolytic agents was 22% higher in the RVO group (p <
      0.0001) and the t50% was 29% longer (p < 0.0001) compared with controls. Only the
      D-Drate was similar in both groups (p = 0.223). The differences remained
      statistically significant after adjustment for fibrinogen, glucose, and platelet
      count. CONCLUSION: The results indicate that in patients with retinal vein
      occlusion, less porous plasma fibrin clots composed of thicker fibrils with the
      reduced permeability and susceptibility to lysis are found, as compared to
      controls. Plasma fibrinogen and C-reactive protein levels are recognized as the
      most important modulators of fibrin function. retinal vein occlusion,
      pathogenesis.

PMID- 24908916
TI  - The use of galantamine in the treatment of post-traumatic oculomotor and
      trochlear nerve palsy.
AB  - PURPOSE: To assess the suitability of galantamine for the symptomatic treatment
      of post-traumatic oculomotor (III) and trochlear (IV) nerve palsy. MATERIAL AND
      METHODS: The routine ophthalmic and strabological examination was performed in
      five patients (4 females and 1 male) at the age of 31 to 57 years (mean 40.7)
      with the post-traumatic ophthalmic complications. Due to the unilateral
      oculomotor and trochlear nerve palsy, which had not resolved within 2-6 (mean
      duration of 4 months) months following traffic accident, galantamine was used.
      Nivalin and Reminyl were administered in iontophoresis and orally, respectively,
      for 10-18 months (mean duration of 14 months). The ocular muscle motion exercises
      and prism correction were also used. RESULTS: The increased range of ocular
      motion (100%), reducing of the angle of strabismus horizontally (40%) and
      vertically (60%), statistically significant extension of palpebral fissure (60%),
      and regression of diplopia (80% total without correction) were observed. The
      binocular vision after treatment in the free- and instrument-space environment
      were also improved (100% simultaneous perception, fusion 80%, stereopsis 60%).
      CONCLUSIONS: The early galantamine administration in patient with n. III and n.
      IV post-traumatic palsy accelerates the resolution of post-traumatic ophthalmic
      symptoms. It is an effective treatment which offers the elimination of
      strabismus, diplopia and ptosis, at the same time improvings ocular movements and
      binocular vision. galantamine, post-traumatic nerve palsy, oculomotor and
      trochlear nerves.

PMID- 24908917
TI  - [Macular morphology and peripapillary retinal nerve fiber layer thickness in
      children with regressed retinopathy of prematurity].
AB  - PURPOSE: morphobiometric evaluation of macula and peripapillary retinal nerve
      fiber layer thickness with the use of high-resolution optical coherence
      tomography in children with a history of regressed retinopathy or prematurity.
      MATERIALS AND METHODS: 18 patients at the age of 8 to 14 years with a history of
      spontaneously regressed retinopathy of prematurity were studied prospectively.
      For statistical purposes a control group of 21 matched subjects at the age of 8
      to 15 years was used. Ophthalmic examination and optical coherence tomography
      were performed in each patient. Peripapillary nerve fibre layer thickness, foveal
      and parafoveal thickness ratio, total macular volume and subfoveal choroidal
      thickness were measured in both groups. RESULTS: in the optical coherence
      tomography, the foveal thickness in children with retinopathy of prematurity was
      significantly higher [269.5 MUm (232-321)] compared to the controls [224.5 MUm
      (207-267)]. The macular volume in the study group was also higher (8.68 mm3). The
      subfoveal choroidal thickness was reduced in study group [321 MUm (112-365)]
      compared to the control group [337 MUm (294-358)]. There was no statistical
      significant difference in total peripapillary nerve fibre layer thickness between
      the two groups. CONCLUSION: The morphobiometric macular changes in eyes with a
      history of regressed retinopathy of prematurity are possibly related to the
      developmental abnormalities, which retinopathy of prematurity is due to the
      presence of the abnormal foveal structure across all retinal layers.

PMID- 24908918
TI  - [The analysis of morphological and functional macular changes after surgical
      treatment of idiopathic macular hole--the single centre experience].
AB  - PURPOSE: to evaluate morphological and functional macular changes after surgical
      treatment of idiopathic macular hole. MATERIAL AND METHODS: a retrospective study
      included 25 patients (30 eyes) who underwent surgery for idiopathic macular hole.
      Male patients constituted 27% and female patients 73% of the study group. Mean
      age was 67 years. All patients underwent pars plana vitrectomy with internal
      limiting membrane peeling and gas tamponade (C3F8 or SF6). We evaluated age, sex,
      best corrected visual acuity as well a optical coherence tomography scans prior
      to surgery and postoperatively. The mean follow-up was 6 months. RESULTS: the
      mean preoperative best corrected visual acuity was 0.15 in Snellen charts (<= 0.1
      - 13 eyes, > 0.1 - 17 eyes) and it increased to 0.5 postoperatively. Five eyes
      were preoperatively classified as stage 2 Gass scale, 13 eyes as stage 3 and 13
      eyes as stage 4. Postoperatively, 25 eyes were assorted as "U" shaped and 5 as
      "V" shape closure. CONCLUSIONS: surgical treatment of macular hole with pars
      plana vitrectomy significantly improves macular function measured by the best
      corrected visual acuity. The "U" shaped closure of macular hole promotes better
      visual outcomes.

PMID- 24908919
TI  - [Vitreous hemorrhages in proliferative diabetic retinopathy treated with pars
      plana vitrectomy--own material].
AB  - The paper presents the retrospective analysis of diabetic patients with vitreous
      hemorrhage due to proliferative retinopathy treated surgically with vitrectomy at
      the Department of Ophthalmology, Medical University of Gdansk in 2008-2010. The
      aim of the study was to evaluate the effect of tamponade and
      antiplatelet/anticoagulation treatment on the recurrence of vitreous hemorrhage.
      MATERIAL AND METHODS: the pars plana vitrectomy was performed in 68 diabetic
      patients (76 eyes) with vitreous hemorrhage secondary to proliferative
      retinopathy. Multiple pars plana vitrectomy was performed in 4 patients, both
      eyes were operated in 8 patients. The patients' age ranged from 27 to 87 years.
      The correlation between the duration of insulin therapy, degree of disease
      progression, antiplatelet/anticoagulation treatment, the time since the last
      vitrectomy, type of vitreous tamponade, and the recurrence of hemorrhages were
      evaluated. The follow-up was 12 months. RESULTS: overall, 83 pars plana
      vitrectomy procedures were performed. Silicone oil was used in 42 procedures, and
      expandable gas in 9 cases. 32 eyes were left without any tamponade. During the
      follow-up the vitreous hemorrhage reoccurred in 10 cases -including 5 eyes left
      without the tamponade, 4 eyes with gas tamponade and 1 eye with silicone oil
      tamponade. CONCLUSIONS: pars plana vitrectomy with silicon oil tamponade ensures
      the effective hemostasis in patients with proliferative diabetic retinopathy.

PMID- 24908920
TI  - [Ocular findings in Polish Armed Forces in Iraq and Afghanistan, a review of
      medical examinations by The Military Medical Commission in Lodz].
AB  - PURPOSE: To determine the prevalence of ocular disorders among Polish soldiers
      returning from Iraq and Afghanistan military campaigns. MATERIAL AND METHODS: A
      retrospective review of medical records of the Military Medical Commission of
      Lodz, Poland was performed. Records of 296 randomly selected soldiers, including
      98 who returned from Iraq in 2004 and in 198 who returned from Afghanistan in
      2012, were assessed. All subjects underwent comprehensive ocular examinations
      according to the military regulations. We used statistical analysis to review the
      results. RESULTS: The incidence of ocular disorders in Iraq and Afghanistan
      groups was 17.3% and 15.1%, respectively. The study revealed that the most common
      disorders among soldiers were refractive errors affecting 6.8% subjects, followed
      by defective color vision (4.7%) and solar retinopathy (3.0%). Combat injuries
      were diagnosed in 3 subjects, including 2 cases of corneal injury and 1 case of
      retinal detachment due to blast exposure. CONCLUSIONS: Combat injuries occurred
      in 1% of soldiers returning from Iraq and Afghanistan military campaigns. There
      were no statistically significant differences between Iraq and Afghanistan groups
      in the incidence of ocular disorders. Solar retinopathy was the most common
      problem related to the long-term exposure to rough climate conditions in both
      groups. ocular findings, Iraq, Afghanistan.

PMID- 24908921
TI  - Congenital optic disc cyst concomitant with persistent hyaloid artery--a case
      report.
AB  - The aim is to present a rare case of solitary malformation in the form of a
      congenital optic disc cyst concomitant with the persistent hyaloid artery. The
      intrabulbar congenital cyst of the optic disc partially covering the medial part
      of the disc was found in a 3-month old infant. B-San ultrasound confirmed the
      presence of the intrabulbar heterogeneous mass (7.0 x 2.5 x 5.4 mm) within the
      vitreous cavity and the concomitant persistent hyaloid artery was shown in Colour
      Doppler Imaging. The axial length of the involved eye was shorter than of the
      healthy one (16.68 mm vs. 18.42 mm). The magnetic resonance imaging of the head
      and orbits performed in the fast spin echo, spin echo and gradient echo sequences
      in T1 and T2-weighted scans revealed the intrabulbar cyst (7.0 x 2.5 x 6.4 mm),
      with sharp margins, whose lower part showed intense contrast enhancement. The
      pericerebral fluid spaces within the frontal and temporal lobes were dilated.
      Intrauterine toxoplasmosis, cytomegaly, protozoan and helminth infections as well
      as metabolic diseases were excluded. Patient leukocyte DNA RB1 gene sequencing
      and negative results of mutation searching excluded retinoblastoma. In a 2-year
      follow-up period, regression of the mass with the absence of ophthalmic
      complications was noted. An important reason for the authors to present the
      discussed case is possible permanent impairment of visual function in patients
      with similar presentation of congenital peripapillary lesions. congenital optic
      disc cyst, developmental anomalies of the optic disc, congenital ocular
      malformations.

PMID- 24908922
TI  - [Isolated congenital hamartoma of retinal pigment epithelium in a long term
      follow-up--case report].
AB  - Retinal pigment epithelium hamartomas are rare, benign tumors, usually with no
      growth potential. The case of hamartoma observed at the Ocular Oncology Service,
      Department of Ophthalmology, University of Medical Sciences in Poznan is
      presented. In 2008 a 30-year-old woman presented with an asymptomatic choroidal
      pigmented lesion. Fundus evaluation revealed a lesion typical of retinal pigment
      epithelium hamartoma. The optical coherence tomography, fluorescein angiography
      and indocyanine green angiography results confirmed the diagnosis of retinal
      pigment epithelium hamartoma. No lesion growth was documented throughout the
      follow-up period of 4 years. Differential diagnosis between congenital retinal
      pigment epithelium hypertrophy (congenital hypertrophy of the retinal pigment
      epithelium) or uveal melanoma was included in the report. retinal pigment
      epithelium hamartoma, fluorescein angiography, optical coherence tomography.

PMID- 24908923
TI  - [Difficulties in surgical management of consecutive exotropia].
AB  - Difficulties in surgical management of consecutive exotropia. Consecutive
      exotropia occurs in formerly esotropic patients without binocular vision, either
      spontaneously or as a result of surgical overcorrection. However, the above
      cannot provide sufficient explanation in all cases. Patients with consecutive
      exotropia mostly complain about aesthetic considerations, although a numerous
      group of patients reports disturbing diplopia. Patients with consecutive
      exotropia require particular attention of the surgeons, due to the difficulties
      in pre-operative assessment and, in turn, in planning thesurgery. The prism
      adaptation test and botulinum toxin injection used in pre-operative diagnostic
      assessment often fail to provide the fully reliable information concerning the
      potential cortical vision suppression, anomalous retinal correspondence and the
      risk of postoperative diplopia (including paradoxical diplopia). Moreover, many
      surgeons emphasize the role of technical difficulties experienced during the
      surgery performed in patients with consecutive exotropia, especially during the
      reoperation. The preoperative assessment in these patients must include the
      forced duction test in order to determine which eye should actually be addressed
      during the surgery. The ocular muscle strength must be balanced during the
      reoperation, which requires extensive surgical experience and often also the
      intraoperative adjustment of the primary surgical plan. However, listening
      patients' concerns regarding satisfactory aesthetic results and considering the
      risk of postoperative diplopia still remain of the utmost importance.

PMID- 24908924
TI  - [Oxidative stress in the pathogenesis of keratoconus].
AB  - Keratoconus is a non-inflammatory corneal disease, which involves changes of the
      corneal shape, due to thinning of the corneal stroma. The pathogenesis of this
      disease has remained unclear, but results of many studies indicate that
      keratoconus is a multifactorial disease. It is hypothesized, that this disorder
      is associated with both genetic and environmental factors. An increase in toxic
      products of lipid peroxidation and nitric oxide pathways, as well as decreased
      levels of some enzymatic and non-enzymatic antioxidants seen in keratoconus,
      suggest an important role of oxidative stress in the pathogenesis of this
      disease. It seems that the interactions of reactive oxygen and nitric species
      with cellular components including nucleic acids, membrane lipids and proteins,
      may activate a series of events leading to keratoconus. The excess amount of
      reactive oxygen and nitric species may induce mitochondrial DNA (mtDNA) damage,
      the extent of which increases in corneas with keratoconus. This damage may
      disturb the mitochondrial process of oxidative phosphorylation, resulting in
      further increase in formation of reactive oxygen and nitric species. Furthermore,
      some elements of oxidative stress can be involved in the activation of certain
      proteinases and release of lysosomal enzymes, which may be important for corneal
      thinning in keratoconus.

PMID- 24908925
TI  - [Oxidative stress in the pathogenesis of Fuchs endothelial corneal dystrophy].
AB  - Fuchs endothelial corneal dystrophy is a disease which occurs after the fourth
      decade of life. This disorder is characterized by the formation of excrescences
      growing from the Descemet membrane, called cormea guttata, and changes in the
      corneal en- dothelial cell density and morphology. The pathogenesis of Fuchs
      endothelial corneal dystrophy is not completely known. Auto- somal dominant mode
      of inheritance observed in some cases of Fuchs endothelial corneal dystrophy
      suggests possible genetic etiology of the disease. Environmental factors also
      seem to be associated with Fuchs endothelial corneal dystrophy. A growing number
      of reports suggest an important role of oxidative stress in this disorder. An
      increased level of toxic products of reactive oxygen species activity and the
      decreased expression of antioxidant enzymes, including thioredoxin reductase,
      metallothione- in 3 and superoxide dismutase 2, were detected in corneas of
      patients with Fuchs endothelial corneal dystrophy. The imbalance between the
      production and neutralization of reactive oxygen species may result in oxidative
      stress exerting a harmful effect on cellular components, leading to molecular and
      cellular damage. Mitochondria may be a key target of alterationsseen in Fuchs
      endothelial corneal dystrophy. An increased level of oxidative mitochondrial DNA
      (mtDNA) damage was detected in corneas of patients with Fuchs endothelial corneal
      dystrophy. Disturbance in mtDNA may cause loss of integrity of inner
      mitochondrial membrane potential and activate the inner apoptotic pathway.
      Consequently, oxidative stress may contribute to the changes in endothelial
      morphology and apoptosis observed in Fuchs endothelial corneal dystrophy.

PMID- 24908926
TI  - [Walenty Hieronim Julian Kamocki (1858-1923)].

PMID- 24908927
TI  - ["Health in the balance"].

PMID- 24908928
TI  - [Infectious diseases caused by carbapenemase-producing Enterobacteriaceae--a
      particular challenge for antibacterial therapy].
AB  - Enterobacteriaceae species such as Escherichia coli and Klebsiella pneumoniae are
      among the most common human pathogens. They are responsible for a wide range of
      community-acquired and nosocomial diseases. Many of the illnesses caused by these
      bacteria could be treated with beta-lactams for several decades. The increasing
      use of carbapenems for the treatment of diseases caused by Enterobacteriaceae
      expressing extended spectrum beta-lactamases, however, lead to the selection and
      spread of carbapenemase-producing pathogens. Such bacteria are not only resistant
      to virtually all beta-lactams, but also to numerous other antibiotics such as
      quinolones, co-trimoxazole, nitrofurantoin, tetracyclines and most
      aminoglycosides. During the last years, carbapenemase-producing
      Enterobacteriaceae have spread into almost all regions of the world. Klebsiella
      pneumoniae carbapenemases (KPC, belonging to Ambler class A), OXA-48 enzymes and
      their derivatives (belonging to Ambler class D) as well as some metallo-beta
      lactamases (Ambler class B) such as NDM, VIM and IMP are the most important
      carbapenemases produced by Enterobacteriaceae strains. In Germany, the metallo
      carbapenemase GIM-1, which has never been proven in bacteria outside Germany, is
      also of clinical significance. There is no established antibacterial therapy for
      these difficult-to-treat diseases. For the treatment of severe diseases caused by
      carbapenemase-producing bacteria, fosfomycin, gentamicin and tigecycline,
      polymyxins such as polymyxin B or colistin as well as carbapenems, are frequently
      applied. Combination antibiotic treatment may be more effective than monotherapy
      for severe ill patients with serious diseases. The most promising new treatment
      options arise with the development of avibactam. This non-beta-lactam beta
      lactamase inhibitor shows good activity against (nearly) all class A and class C
      beta-lactamases (including strains expressing class A carbapenemases and/or
      derepressed AmpC enzymes) as well as OXA-48 carbapenemases. It may be used
      successfully in combination with ceftazidime, ceftaroline or aztreonam.

PMID- 24908929
TI  - [More therapeutic safety through individual DNA analysis].

PMID- 24908930
TI  - [Abstinence rates among varenicline are highest].

PMID- 24908931
TI  - [Development in young adults and risk for atherosclerosis].

PMID- 24908932
TI  - [High doses of selenium and vitamin E administration increased risk of cancer].

PMID- 24908933
TI  - [ASCO highlights in the treatment of metastatic melanoma].

PMID- 24908934
TI  - [Feelings of depression should be taken more seriously].

PMID- 24908935
TI  - [State of the art in pharmacotherapy].

PMID- 24908936
TI  - [Are sleeping men and women different?].

PMID- 24908938
TI  - [Acid inhibition leads to vitamin b12 deficiency].

PMID- 24908937
TI  - [Two-dose vaccination schedule for younger girls].

PMID- 24908939
TI  - [Importance of sugar and sugar substitutes].

PMID- 24908940
TI  - [Bacteria as drug producers in marine sponges].

PMID- 24908941
TI  - [New infections of the gastrointestinal tract].

PMID- 24908942
TI  - [Antibiotic use does not always make sense].

PMID- 24908943
TI  - [Keep kidney function in mind].

PMID- 24908944
TI  - [Cardiac arrhythmias and superior vena cava syndrome revealing a Richter's
      syndrome].
AB  - Richter's syndrome is the aggressive transformation of chronic lymphocytic
      leukemia in a diffuse large cell lymphoma. The locations and the clinical
      manifestations are varied. We report the case of a Richter's syndrome revealed by
      cardiac arrhythmias and superior vena cava syndrome in a patient of 78 years
      followed during 2 years for chronic lymphocytic leukemia.

PMID- 24908945
TI  - [Neurologic disorder complicating a cervical cancer].
AB  - A 47-year-old patient is admitted to the hospital for visual disorders and
      paresthesia on her left hemiface and her superior left limb. Symptoms appeared
      about a month before. The patient is currently under treatment for a non
      metastatic cervical adenocarcinoma, of stage IIIb according to FIGO. Further
      exams show bilateral hypodense cerebral lesions of unknown origin despite many
      complementary tests, among which a transthoracic and transoesophageal
      echocardiography, autoimmune and infectious testings. During her hospitalisation,
      the patient's condition worsens on the neurologic and cardiac levels in spite of
      a wide-spectrum empirical antibiotherapy initiated with the presumed diagnosis of
      infectious endocarditis. The repetition of cardiac echocardiographies ends up
      showing a nodule on the mitral valve. The context of neoplasia, negative
      hemocultures and serologies, lead us to evoke the diagnostic of marantic
      endocarditis even though this kind of complication was rarely described in cases
      of cervical neoplasia. An anticoagulant treatment is therefore initiated and the
      patient's state will progressively improve, at least at first.

PMID- 24908946
TI  - [Delirium in the elderly].
AB  - Delirium in the elderly is common but unfortunately underdiagnosed. The
      consequences could be significant such as an increase of the mortality in the
      hospital, loss of autonomy and increased risk to be institutionalized. The
      presentation of the delirium could be hyperactive, hypoactive or mixed. The
      predisposing and precipating factors are well known. The physiopathology is not
      yet well defined but the inflammation and the neuromediators are involved. It is
      important to develop primary and secondary prevention, but also to propose a
      follow in memory clinics for all elderly people who having suffered from delirium
      during hospitalization because a confusional state could be the first step
      towards future dementia.

PMID- 24908947
TI  - [Sickle cell disease patients, sickness and medical accompanying questioning
      related to specific adolescent period].
AB  - The sickle cell disease is a genetic disease of the hemoglobin, also called
      sickle-cell anemia. It is the most common genetic disease in the world. It is
      nevertheless still enough underestimated by the general public and even sometimes
      by the medical world. The patients who are affected suffer, besides a chronic
      anemia, extremely painful vaso-occlusive crises and possibly diverse
      complications. Because of the extension of their life expectancy, due to
      important medical progress, the patients are required to go to the hospital for
      adults. The object of this article is to try to draw a portrait of these patients
      and the multiple obstacles with wich they are confronted. These teenagers or
      grown-up young people have indeed to face important physical problems wich have
      significant psychological impact. How do they reconcile adolescentaire crisis and
      management of the disease? How can the hospital welcome at the best these "new"
      patients?

PMID- 24908948
TI  - [Cervical medullar infarction in multileveled discopathy].
AB  - Spinal cord infarction is a rare but devastating pathology causing acute
      neurological deficits. The incidence has been estimated to 1% of all strokes. In
      that case report, our patient has presented anterior spinal artery infarction in
      C5-C6. The only risk factor founded was a multileveled discopathy wich is known
      to be an uncommon cause of anterior spinal artery syndrome.

PMID- 24908949
TI  - [Bilateral adnexal masses during pregnancy].
AB  - The presence of adnexal masses during pregnancy is a rare situation but due to a
      broader use of sonography; its occurrence is increasing. Their management
      essentially relies on imagery. We report the case of an 18 weeks-pregnant women
      presenting bilateral teratomas visualized by RMI. She was successfully treated by
      laparoscopy. This paper approaches the management of adnexal masses during
      pregnancy. The epidemiology, possible complications, diagnostic approach and the
      therapeutic management are discussed.

PMID- 24908950
TI  - [The definition of death and organ retrieval: a persisting philosophical
      controversy].
AB  - Since the publication of the recommendations of the ad hoc committee of the
      Harvard Medical School to examine the definition of brain death in 1968,
      philosophical discussions concerning the licit character of organ retrieval in
      brain dead patients never ceased. The present paper summarizes the main arguments
      of supporters and opponents of this procedure.

PMID- 24908951
TI  - [Heart rupture, post-infarction].

PMID- 24908952
TI  - [The Belgian and French medicine and the "Ordres" facing the "jewish question"
      during the Second World War].
AB  - The attitude of the medical community and the "Ordres" to the "jewish question"
      differs in Belgium and France. This difference originates before the Second World
      War. Xenophobia and antisemitism were stronger in France. In addition, the
      Belgian capitulation of May 1940 and the armistice of June 22 in France do not
      represent the same situation. In France, a legal government, under the direction
      of Marshal Petain, took a series of xenophobic measures of which the Jews were
      the first victims. In Belgium, in the absence of any government, the General
      Secretaries in Ministries were the ones who had to apply the antijewish measures
      dictated by the German occupant. By law, they could not legislate on the
      political level. The "Ordre", of French physicians was created in late 1940 by
      the Vichy government. In Belgium, the "Ordre " had existed since 1938 but had
      been unable to meet in the absence of implement decrees. An "Ordre bis" was
      created in late 1941, the legality of which was questioned by many lawyers and
      physicians. The French "Ordre" was to apply the antijewish measures by taking
      responsibility for the selection of Jewish physicians entitled to practice. In
      Belgium, the "Ordre" frowned upon by the physicians, played no official role in
      this regard. It simply applied the antijewish measures dictated by the Germans
      without protesting. After the conflict, the leaders of the "Ordres" had a
      different fate in both countries. In France, they escaped sentences. In Belgium,
      they were heavily condemned.

PMID- 24908953
TI  - [Sarcoidosis--granulomatosis: the modern view of the etiology and pathogenesis
      with clinical cases review].
AB  - Diagnostic criteria of sarcoidosis were offered in the 60-ies of XX century,
      however today the problem of sarcoidosis is difficult for understanding the
      different specialists and early detection. The development of laboratory
      diagnostic of viral infections and introduction of polymerase chain reaction
      (PCR) has greatly improved the level of diagnosis of herpes infections, reveal
      the previously unknown etiology of many diseases: sarcoidosis (granulomatosis),
      migraine, multiple sclerosis, cystic prenatal brain damage, convulsions,
      Hodgkin's disease and others. Sarcoidosis is the set of clinical symptoms
      (fatigue, shortness of breath, coughing, heaviness in the chest), laboratory,
      radiological and histopathological data that allow the doctor to diagnose,
      predict prognosis and treatment policy. Most often, sarcoidosis affects the lungs
      and thoracic lymph nodes. In the last period for 2011-2013 in 2930
      immunologically tested patients the sarcoidosis was confirmed in 146. Primarily
      these patients were exposed to different diagnosis--COPD, pneumonia,
      tuberculosis, lung cancer. Among patients with sarcoidosis on the first place in
      frequency of detection were EBV and HHV-6. We were the first in 2000, described
      the Epstein-Barr virus as the causative factor of sarcoidosis, and has been
      hypothesized the immunopathology of sarcoidosis and principles of individual
      immunotherapy with a resolution of the granulomatous process in 92 % of cases.
      Subsequently, this association has been and illustrates the relationship to other
      viruses (HHV-6, HHV-8) demonstrated by other authors.

PMID- 24908954
TI  - [Clinical course and characteristics of cellular and humoral immunity in patients
      with allergic rhinitis].
AB  - In research the condition cellular and humoral immunity is defined at allergic
      rhinitis--AR (n = 45) for an estimation of mechanisms pathogeny this disease. The
      AR in 76% of cases has the hereditary nature mainly from outside mothers (36%),
      begins more often at children's and teenage age (88%) and in 44% is accompanied
      by other allergic pathology. In structure of a sensibilization of patients the
      allergic rhinitis the basic place is occupied with pollen, household, fungoid and
      epidermal allergens, allergic reaction (83% of cases) thus prevailed. As a result
      of the spent researches rising of relative quantity CD4+CD25+Foxp3+ regulatory T
      cells is taped, at the same time rising of an average level of the general IgE-
      (198,20 +/- 11,42) IU/ml is noted. In cytokine regulations at patients an
      allergic rhinitis rising IL-4 and depression IL-10 is noted. Thus, the conducted
      research suggests that an allergic rhinitis--disease with involving in process of
      regulation of the immune answer of certain type regulatory T of cells.

PMID- 24908955
TI  - [Methods of mathematical modeling in morphological diagnostics of Chernobyl
      factor influence on the testes of coal miners of Donbas--the Chernobyl disaster
      fighters].
AB  - The morphometric estimation of parenchyma and stroma condition included the
      determination of 29 parameters in testicles at 27 persons. The mathematical model
      of morphogenesis of testicles was created by Bayes' method. The method of
      differential diagnosis of testicles tissues' changes conditioned by the influence
      of the Chernobyl factor and/or unfavorable terms of the work in underground coal
      mines have been worked out. Its practical use provides exactness and reliability
      of the diagnosis (not less than 95%), independence from the level of the
      qualification and personal experience of the doctor, allows us to unify, optimize
      and individualize the diagnostic algorithms, answer the requirements of
      evidential medicine.

PMID- 24908956
TI  - [Parallel pharmacological correction of myocardial dysfunction, cognitive and
      psychopathological disordres in patients with congestive heart failure].
AB  - Was examined 92 patients with congestive heart failure III-IV FC with fraction of
      emission left ventricle < 45% against coronary artery disease. Patients of
      control group received basic therapy (according to recommendations of the
      Ukrainian society of cardiology), the 1 group--in addition received a preparation
      of Vazonat within 15 days intravenously in a dose of 1000 mg a day further are
      out-patient within 1 month on 250 mg 3 times per os; the 2 group--under the same
      scheme a preparation of Vazonat and a day tranquilizer of Adapto in a dose of 500
      mg twice a day throughout all term of supervision. It is established that
      addition of Vazonat to basic treatment leads to additional effect concerning
      improvement of indicators cardio-hemodynamic, to improvement congestive
      functions. Joint appointment of preparations of Vazonat and Adaptol against basic
      treatment leads to more expressed improvement congestive functions, to
      progressive reduction of degree of trouble, depression.

PMID- 24908957
TI  - [Hyperhomocysteinemia and cardiovascular risk profile in ischemic heart disease
      and acid peptic disease comorbidity patients].
AB  - Present article is devoted to the study of the clinic features of ischemic heart
      desease associated with acid peptic disease. It was shown the more evident
      increase of myocardial infarction risk in associated pathology patients. Such
      results have to be caused by the special risk factor. As such factor we desided
      to study the hyperhomosysteinemia. During research there were discovered that the
      lowest vitamin B12 serum level and the highest homocysteine serum level have been
      registrated in associated pathology (ischemic heart disease and acid peptic
      disease according to long-term proton pump inhibitor use) patients. It was shown
      evident correlation between that changes and dyslipidemia.

PMID- 24908958
TI  - [Effect of sanatorium treatment on endothelial function in children with primary
      arterial hypertension].
AB  - To study the effect of sanatorium treatment (ST) using sodium chloride baths and
      metabolic drug mildronat on the dynamics of the ambulatory blood pressure
      monitoring (ABPM), markers of endothelial function in children with primary
      arterial hypertension (PAH). ABPM and held defined level of asymmetric
      dimethylarginine (ADMA), endothelin-1 (ET-1) and nitric oxide (NO) in the serum
      of 114 children with PAH aged 12-17. The positive dynamics of ABPM in all groups,
      but significantly (P < 0.05) decrease in mean BP was noted in the group with
      combined ST using sodium chloride baths. When analyzing the level of NO a
      positive trend (P < 0.01) in the group was using metabolic therapy, but
      significantly (P < 0.001) pronounced effect was observed when it is combined
      balneotherapy and metabolic therapy. Analysis of ET-1 and ADMA at ST in
      conjunction with therapy and metabolic rate of sodium chloride baths there was a
      significant (P < 0.01) decrease in these parameters in comparison with those
      before treatment. In children with PAH have been identified violations of the
      functional activity of the endothelium, which is reflected in increased levels of
      ET-1, ADMA and reducing NO. Conducting rehabilitation inclusion complex
      balneotherapy and metabolic therapy helps to reduce average daily blood pressure,
      normalization of functional activity of the endothelium as a normalization of the
      synthesis of NO (P < 0.,001), a significant decrease of ET-1 (P < 0.01) and ADMA
      (P < 0.01).

PMID- 24908959
TI  - [Hemodynamics, oxygen transport and perioperative intensive care evaluation in
      newborns with surgical pathology].
AB  - The aim of the work was to develop criteria of perioperative intensive therapy
      efficiency in surgical neonates by hemodynamic, acid--base status, oxygen
      transport and pulmonary hydration studying and evaluating. The study of
      hemodynamics, oxygen transport, pulmonary hydration was performed in 69 infants
      with surgical pathology. In 36 children neuroaxial central blockades were used on
      the background of general anesthesia. The criteria of preoperative preparation
      effectiveness--balanced oxygen regime--3-3.5 units; positive central venous
      pressure--3-4 sm w. c.; hourly urine output of at least 1 ml/(kg x h);
      transthoracic impedance is not less than 19 ohms (prevention of pulmonary edema).
      In group I hemodynamic variations were minimal compared with infants of the II
      groups that is associated with better analgesic effect of caudal-epidural
      blockades.

PMID- 24908960
TI  - [Non-specific bronchial hyper-responsiveness and polymorphysm of xenobiotics
      biotransformation GSTM1 and GSTT1 genes under neutrophilic bronchial asthma in
      children].
AB  - With a view to study the effect of genes GSTT1 and GSTM1 deletion on the non
      specific bronchial hyperresponsiveness in children with neutrophilic bronchial
      asthma (BA) 46 school age children having neutrophilic BA (1st clinical group)
      and their 48 coevals with eosinophilic phenotype of the disease (2nd clinical
      group) were subjected to a complex examination at the pulmo-allergologic
      department of the regional child clinical hospital of Chernivtsi. The study
      proved that genotype T1+M1del was more frequently registered in patients with the
      neutrophilic phenotype of the disease, and genotype T1delM1del was equifrequent
      in patients with different types of the inflammation of the respiratory ways. In
      patients with neutrophilic BA and deletion polymorphism of genes GSTT1 and GSTM1,
      there was a tendency to decreasing of the bronchial lability index through the
      decrease of bronchodilation, and bronchial response to histamine occurred to be
      higher than in children with the absence of polymorphism of the referred genes of
      the xenobiotics biotransformation system.

PMID- 24908961
TI  - [Additional chromosomal abnormalities in dynamic of target therapy for chronic
      myeloid leukemia in children and adolescents].
AB  - Chromosomal abnormalities of bone marrow cells in dynamic chronic myeloid
      leukemia (CML) with bcr-abl-tyrosinkinase inhibitor (400 mg/m2) in 34 children
      and adolescent were estimated. Appearence of additional chromosomal abnormalities
      such as del(16)(q22), del(11)(q23), del(6) (q23), del(21)(q12), trisomy
      chromosome 8, additional neartetraploid clones were evidence about tumor cells
      resistence to therapy in children and adolescent.

PMID- 24908962
TI  - [P300 potential parameters at the stages of formation of the subcortical vascular
      dementia in elderly].
AB  - Auditory P300 latency and amplitude values were assessed in 11 elderly persons
      without cognitive impairments (WCI), mean age--(70.73 +/- 4.24) years, 20
      patients with subcortical vascular mild cognitive impairment (SCMCI), mean age-
      (75.35 +/- 5.48) years and 20 patients with subcortical vascular dementia
      (SCVaD), mean age (75.80 +/- 6.51) years. Obtained data suggest that P300 latency
      value increase at the stages of the SCVaD progression. Mean values of P300
      latency were (341.09 +/- 107.70) ms in WCI group, (655.70 +/- 87.08) ms in SCMCI
      patients, (732.45 +/- 74.64) ms in SCVaD patients. There were significant
      differences between the groups. This parameter allows differentiating patients
      with SCMCI from elderly persons WCI, and patients with SCVaD from SCMCI.
      Increasing P300 latency has sufficient relationship to severity and specificity
      of cognitive deficit of SCVaD stages development reflecting progressive
      deterioration of attention, working memory, kinetic and regulator praxis.

PMID- 24908963
TI  - [Characteristics of gonadotropic function in patients with pubertal uterine
      bleeding in the modern society].
AB  - The character of gonadotropin changes, which have been studied in patients with
      pubertal uterine bleeding, enable the authors to establish that its nature
      depends on the body weight value against the background of uterine bleeding. The
      study provides evidence that only half of all patients with bleeding has normal
      hormone levels. Disorders in gonadotropin levels have been registered in one
      third of our patients. The authors have also revealed that bleeding in patients
      with body weight excess significantly more often is accompanied by the increased
      LH and PRL morning levels and LH/FSH ratio, which occurs against the background
      of hypothalamic-pituitary function activation. Positive effect of insulin level
      on the LH production has been found in patients of the above group.

PMID- 24908964
TI  - [Application of algorithms for treatment of dentition anomalies complicated by
      crowding of teeth].
AB  - 100 patient, aged between 4 and 42, with various dentition anomalies exacerbated
      by crowding of lower and upper teeth, have been examined and given orthodontic
      treatment. The orthodontic treatment involved a combination method in conjunction
      with functional (biological), machine, surgical and prothetic methods. The
      analysis of the results of this study shows that the treatment algorithms used in
      this study could be recommended for clinical application.

PMID- 24908965
TI  - [Monitoring of knowledge level in ambulatory patients with arterial
      hypertension].
AB  - Monitoring results of current awareness level of dispensary patients with
      arterial hypertension are presented in the article. Awareness-raising activities
      for patients with arterial hypertension were developed by information and
      education work and communications increasing; effective target medical and social
      programs developing and implementing.

PMID- 24908966
TI  - [Structure and function of the heart according to body weight in men of working
      age].
AB  - The scientific structure and function heart in 65 working age men according to
      weight and body composition. The shown that the excess body weight observed a
      significant increase in the size and volume left ventricle of the heart and
      myocardial mass. The percentage of muscle mass in the body of the patients
      positively correlated with systolic function of the heart, while the percentage
      of body fat had a negative correlation with this index. The shown that the
      individualization of health exercise should take into account the percentage of
      the active body weight and fat mass in the body, since the high content of fat
      intense exercise can lead to heart and remodeling worsening left ventricular
      systolic function heart, while increasing BMI due to muscle does not contribute
      to the structural and functional reorganization of the heart.

PMID- 24908967
TI  - [The link between food intolerance and weight: a new perspective in the treatment
      of obesity].
AB  - In the article is presented the correlation between body weight and food
      intolerance to certain products, often associated with the development of food
      intolerances.

PMID- 24908968
TI  - [Influence of cryoglobulinemic syndrome and insulin resistance on the progression
      of liver cirrhosis in patients with chronic hepatitis C].
AB  - The article presents the results of analysis of the frequency of detection of
      cryoglobulinemic syndrome (CGS) and insulin resistance (IR) in patients with HCV
      associated liver cirrhosis (LC) depending on its stage. There were also evaluated
      clinical and laboratory features of the disease. The study involved 72 patients
      with chronic hepatitis C who were divided into 3 main groups according to the
      presence of LC. The I group included 32 patients with chronic hepatitis C without
      LC. The II group consisted of 19 patients with compensated HCV-associated LC and
      III group included 21 patients with decompensated LC. It was shown that terminal
      stages of the LC (class B-C by Child-Pugh) are characterized by more frequent
      presence of IR and CGS with more severe clinical picture, which may be caused not
      only by the influence of the hepatitis C virus (HCV), but also by the progression
      of LC.

PMID- 24908969
TI  - [Clinical features and characteristics of community-acquired pneumonia associated
      with iron deficiency anemia in children of pre-school age].
AB  - The most common clinical signs of community-acquired pneumonia associated with
      iron deficiency anemia in children of pre-preschool age are defined. Indicators
      of immunity cellular link in children with community-acquired pneumonia are
      studied. It is established that acute illness is characterized by disturbances in
      cellular immunity that are more expressed in patients with concomitant iron
      deficiency anemia.

PMID- 24908970
TI  - [Effect of high dose tamoxifen therapy in conservative treatment of patients with
      III-IV stages of non-small cell lung cancer].
AB  - Lung cancer is currently the leading cause of cancer-related death. The
      effectiveness of treatment of locally advanced and metastatic non-small cell lung
      cancer (NSCLC) remains low. One the promising new directions in NSCLC treatment
      is the inclusion of antiestrogens (tamoxifen) to standard chemotherapy regimens.
      Expression of estrogen (Eralpha) and progesterone (PR) receptors in the tumor
      tissue, objective effect and NSCLC patients' survival at chemohormonal treatment
      with tamoxifen use were analysed. ERalpha and PR-receptor status study in
      patients with NSCLC revealed presence of expression only in 1 (2%) patient. One
      year and median survival (55% and 13.1 months respectively) at high-dose
      tamoxifen therapy use in combination with chemotherapy were established to be
      significantly higher (P = 0,00055) than in patients, which received only
      chemotherapy (32% and 9.5 months respectively).

PMID- 24908971
TI  - [Effectiveness of adjuvant chemotherapy in patient with early stages of non-small
      cell lung cancer depending on proliferation index of tumor].
AB  - Adjuvant chemotherapy is a debatable question in patients with early stages of
      non-small cell lung cancer (NSCLC). Prognostic/predictive markers should be used
      for individualizing prescription of adjuvant chemotherapy. The aim of our study
      was to investigation effectiveness adjuvant chemotherapy in patients with early
      stages of NSCLC due to proliferation index of tumor. We included in study 254
      patients with I-II stages of NSCLC that conducted treatment in department of
      thoracic surgery Zaporozhye regional clinical oncology center since June 2008 to
      December 2012. Expression Ki-67, proliferation marker, measured in 95 patients
      that used adjuvant chemotherapy and in 122 patients with out additional
      treatment. Measuring of proliferation index was don by next method: 0-5%
      immunopositive cells--0 point, 6-25%--1 point, 26-50%--2 point, 51-75%-- 3 point,
      76-100%--4 point. High expression was > or = 2 points. RESULTS: Mean of
      proliferation index in patients with early stages of NSCLC was 37.6% (95% CI,
      33.8-41.5%). Median of survival in patients with II stage of NSCLC was 39.7 month
      if patients conducted adjuvant chemotherapy and 21.4 month with out treatment. It
      was tendencies increasing survival in patients with II stage of NSCLC after
      adjuvant chemotherapy, but it was not statistically significant (P = 0.16).
      Survival patients with high proliferation index was 10.5 month--75 percentile, 18
      month--median, 29.9 month--25 percentile. In patients after adjuvant chemotherapy
      75 percentile of survival was 34.4 month, median of survival not complete.
      Survival differences of two group were statistically significant (P < 0.0001).
      Thus individualization of prescription adjuvant chemotherapy in patient with
      early stages of NSCLC helps improves results of treatment and avoid unreasonable
      toxic therapy.

PMID- 24908972
TI  - [Rehabilitative treatment of patients with complicated spinal injuries and
      trophic disorders in specialized neurological center].
AB  - The analysis of treatment results 132 patients with consequences with spine
      injury and the presence of venous disorders which in conditions of specialized
      health resort management system applied in complex restorative treatment, which
      includes patogeneti no-reasonable comprehensive preparation, surgery and further
      restorative treatment. Based on the analysis and systematization of the results
      developed diagnostic and therapeutic algorithm and algorithm for planning
      surgical tactics.

PMID- 24908973
TI  - [Characteristics of psychotherapeutic support for patients with traumatic
      encephalopathy].
AB  - As a result of psychological research on 127 patients with traumatic
      encephalopathy and complex treatment methods with the inclusion of psychotherapy
      marked positive dynamics of the psychological status, and found three main
      syndromes (asthenic, hypochondriac, hysterical) and concluded the most effective
      methods of psychotherapy.

PMID- 24908974
TI  - [Characteristics of psychosexual development of married couples with epilepsy in
      the husband in aspect of sexual disharmony formation].
AB  - Features of formation of sexual disharmony of married couples with epilepsy at
      the husband are studied. The role of psychosexual development in formation of
      sexual violations and a matrimonial disadaptation is defined.

PMID- 24908975
TI  - [Professional risk assessment for modern pesticides during their application in
      the horticulture].
AB  - The work conditions on application of modern pesticides Masai, Regalis and Bellis
      for apple orchards protection have been researched. We show that total risk of
      hazard influence of tebufenpyrad, prohexadione-calcium, pyraclostrobin and
      boscalid on agricultural workers under condition of complex entry in body through
      skin and respiratory tracts is permissible. We proved that application of studied
      preparations is not dangerous for workers in case of abidance of agrotechnical
      and hygienic regulations.

PMID- 24908977
TI  - [Endocrine diseases: progress in diagnosis and treatments. Editorial: update on
      diagnostic and treatment strategies in endocrine diseases].

PMID- 24908976
TI  - [Oxidative stress and antioxidant therapy with alpha-lipoic acid inclusion in
      acute poisoning by herbicide based on 2,4-dichlorphenoxyacetic acid].
AB  - In patients with acute poisoning amine salt herbicide 2,4-D develops oxidative
      stress with simultaneous inhibition of intracellular and extracellular
      antioxidant factors. These changes are more pronounced with neurological
      disorders that occur in conjunction with a toxic damage of liver or heart. The
      inclusion of a comprehensive detoxification therapy alpha-lipoic acid not only
      promotes a more pronounced therapeutic effect but also an earlier recourse
      cytolytic syndrome, a marked recovery of levels of malondialdehyde and indices of
      antioxidant system (superoxide dismutase and ceruloplasmin) than for patients in
      the comparison group.

PMID- 24908978
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: I. Anterior
      lobes of the pituitary; 1. Recent progress in diagnosis and treatment of
      acromegaly].

PMID- 24908980
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: I. Anterior
      lobes of the pituitary; 3. Diagnosis and treatment of prolactinoma].

PMID- 24908979
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: I. Anterior
      lobes of the pituitary; 2. Cushing syndrome].

PMID- 24908981
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: II. Posterior
      pituitary-approach for hyponatremia].

PMID- 24908982
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: III. Thyroid
      gland; 1. Approach to thyroid hormone abnormality].

PMID- 24908983
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: III. Thyroid
      gland; 2. The management approaches to thyroid nodules discovered incidentally on
      diagnostic imaging].

PMID- 24908984
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: IV. A
      practical approach to diagnosis and management of abnormalities in calcium
      metabolism].

PMID- 24908985
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: V. Adrenal
      cortex; 1. Early diagnosis and treatment of adrenal insufficiency].

PMID- 24908986
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: V. Adrenal
      cortex; 2. What can we do for the proper diagnosis and treatment of primary
      aldosteronism?].

PMID- 24908987
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: VI. Early
      detection of pheochromocytoma].

PMID- 24908988
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: VII.
      Adrenogenital syndrome and gonadal disorders experienced by internist].

PMID- 24908989
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: VIII.
      Diagnosis and treatment of pancreatic neuroendocrine tumors].

PMID- 24908990
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: IX. Recent
      topics; 1. How to prevent fracture with antiosteoporosis drugs: an update].

PMID- 24908991
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: IX. Recent
      topics; 2. Thyroid disease in pregnancy].

PMID- 24908992
TI  - [Endocrine diseases: progress in diagnosis and treatments. Topics: IX. Recent
      topics; 3. Multiple endocrine neoplasia].

PMID- 24908993
TI  - [Discussion meeting on the clinical pearls to diagnose endocrine disorders].

PMID- 24908994
TI  - [Case report; An autopsy case of respiratory failure due to Strongyloides
      stercoralis infection].

PMID- 24908995
TI  - [Case report; A Japanese case of familial Mediterranean fever with pleurisy].

PMID- 24908996
TI  - [Case report; A case of two female siblings with Paragonimus westermani
      infection].

PMID- 24908997
TI  - [The cutting-edge of medicine; the pathology and new treatment of ADPKD].

PMID- 24908998
TI  - [Report from the 40th Hokuriku Chapter Educational Seminar: overview and
      evaluation results of the second abdominal emergency medical training course
      (AbdEMeT)].

PMID- 24908999
TI  - [Series: Clinical study from Japan and its reflections; diabetic retinopathy and
      microalbuminuria can predict macroalbuminuria and renal function decline in
      Japanese type 2 diabetic patients: Japan Diabetes Complications Study (JDCS)].

PMID- 24909000
TI  - [Series: For attending physicians; seeking to understand the diversity of
      medicine; a practical approach to community medicine].

PMID- 24909001
TI  - [Series: Physicians and disaster medical care; Third stage. Management and
      education for disaster medicine: disaster medical cordination system. (2). The
      Great East Japan earthquake].

PMID- 24909002
TI  - [How does the physician interpret the patient's narrative at it relates to the
      physical exam?: A case with weight loss, hyponatremia and malaise].

PMID- 24909003
TI  - How much is "it" going to cost?

PMID- 24909004
TI  - Public health in Arkansas--where are we now?

PMID- 24909005
TI  - Patient Centered Medical Home update.

PMID- 24909006
TI  - What it means...

PMID- 24909007
TI  - The distribution and public health consequences of releases of chemicals intended
      for pool use in 17 states, 2001-2009.
AB  - To keep swimming pool water clean and clear, consumers purchase, transport,
      store, use, and dispose of large amounts of potentially hazardous chemicals. Data
      about incidents due to the use of these chemicals and the resultant public health
      impacts are limited. The authors analyzed pool chemical release data from 17
      states that participated in the Agency for Toxic Substances and Disease
      Registry's chemical event surveillance system during 2001-2009. In 400 pool
      chemical incidents, 60% resulted in injuries. Of the 732 injured persons, 67%
      were members of the public and 50% were under 18 years old. Incidents occurred
      most frequently in private residences (39%), but incidents with the most injured
      persons (34%) occurred at recreational facilities. Human error (71.9%) was the
      most frequent primary contributing factor, followed by equipment failure (22.8%).
      Interventions designed to mitigate the public health impact associated with pool
      chemical releases should target both private pool owners and public pool
      operators.

PMID- 24909008
TI  - Environmental survivability and surface sampling efficiencies for Pseudomonas
      aeruginosa on various fomites.
AB  - The study described in this article evaluated surface survivability of culturable
      Pseudomonas aeruginosa by time and type (glass, stainless steel, and laminate)
      using two sampling techniques: contact plates and surface swabs. Recovery of P.
      aeruginosa decreased logarithmically over time and varied by surface type. P.
      aeruginosa survival averaged 3.75, 5.75, and 6.75 hours on laminate, glass, and
      stainless steel, respectively. Culturable P. aeruginosa loss on stainless steel
      and glass were not different (p > .05); however, laminate had significantly
      greater loss at each time point than either glass or stainless (p < .05). A
      comparison of surface swab and contact plate collection efficiencies found no
      significant difference for laminate surfaces. Swabs, however, had a higher
      collection efficiency than contact plates (p < .05). For the first time, the
      authors report P. aeruginosa mean survival time of 3.75-6.75 hours on clinically
      relevant surfaces, with P. aeruginosa on stainless steel surviving the longest.
      Their data also indicate that culturable surface sampling appears to most
      accurately represent actual P. aeruginosa surface loading when swab sampling is
      used.

PMID- 24909009
TI  - Use of household bleach for emergency disinfection of drinking water.
AB  - Household bleach is typically used as a disinfectant for water in times of
      emergencies and by those engaging in recreational activities such as camping or
      rafting. The Centers for Disease Control and Prevention recommend a concentration
      of free chlorine of 1 mg/L for 30 minutes, or about 0.75 mL (1/8 teaspoon) of
      household bleach per gallon of water. The goal of the study described in this
      article was to assess two household bleach products to kill waterborne bacteria
      and viruses using the test procedures in the U.S. Environmental Protection
      Agency's Guide Standard and Protocol for Testing Microbiological Purifiers.
      Bleach was found to meet these requirements in waters of low turbidity and
      organic matter. While the test bacterium was reduced by six logs in high turbid
      and organic-laden waters, the test viruses were reduced only by one-half to one
      log. In such waters greater chlorine doses or contact times are needed to achieve
      greater reduction of viruses.

PMID- 24909010
TI  - National expenditures, jobs, and economic growth associated with indoor air
      quality in the United States.
AB  - While a number of studies have addressed the economic cost associated with
      adverse health and productivity effects of poor indoor air quality (IAQ), few
      have addressed the value of economic expenditures and job creation associated
      with this industry. This article estimates that the annual sale of IAQ products
      and services is valued at $18-$30 billion and is associated with approximately
      150,000-250,000 current jobs. Compared with other familiar industries, the IAQ
      market remains relatively small. Given the close association between good IAQ and
      both job performance of adults and learning performance of children, however, the
      expenditure to maintain good IAQ in commercial and educational facilities is a
      useful complement to programs designed to improve education and economic growth.

PMID- 24909011
TI  - Update on the model aquatic health code.

PMID- 24909013
TI  - Fifty-five jobs of the future: part two.

PMID- 24909012
TI  - CDC's national environmental public health tracking network classroom modules.

PMID- 24909014
TI  - Twelve keys to the successful association of the future.

PMID- 24909015
TI  - An integrated approach to individualized optimal dose estimation of medication by
      means of dosing adjustment measures and Bi-Digital O-Ring Test.
AB  - Posology concerns science and system of dosage. Conventionally the dosage systems
      of measurement are the apothecaries' and metric systems and the dosage
      calculation for each individual patient has been suggested according to several
      available methods, namely Clark's Rule, Fried's Rule, Young's Rule, body surface
      area, or mg/kg, etc. There are many factors affect the availability of a drug to
      its site of action in the body, and their relation to the time course of drug
      action and variation in each drug response with or without the other drugs taken
      simultaneously. The correct dosage requires meticulous and accurate calculation.
      In busy offices, some may feel the dosage calculation is tedious. This article
      reviews the conventional methods of dosage calculations and the allergy tests,
      followed by describing a simple way to determine the proper dosage for each
      patient by simplifying the Clark's concept based on the body weight and verify
      the optimum dosage with Bi-Digital O-Ring Test minimize the adverse drug
      reactions and to increase safety for drug administration.

PMID- 24909016
TI  - Unique aspect of Tibetan medicine.
AB  - Tibetan medicine is known as the knowledge of healing in the Four Tantras, the
      main medical text studied by Tibetan doctors. In the 8th century, King Trisong
      Deutsen (718-785 CE) invited eminent physicians from India, China, Persia, East
      Turkestan, Mongolia, and Nepal for the First International Medical Symposium in
      Samye, Tibet and ordered his personal physician Elder Yuthog Yonten Gonpo (708
      833 CE), who lived 125 years, and participated in this conference to summarize.
      By combining all the information available and presented during this symposium,
      he compiled the Four Tantras. He established the Tanadug medical school at
      Menlung in Kongpo, Southern Tibet in 763 CE, and worked for the propagation of
      Tibetan medicine. He is considered an emanation of Medicine Buddha, who is a
      symbol of mental and physical well being. In his left hand, the Medicine Buddha
      clasps a begging bowl with long-life nectar, signifying immortality, and in his
      right, the Chebulic myrobalan (Haritaki), a symbol of good health. Chebulic
      myrobalan, Belleric myrobalan, and Emblic myrobalan are together called the "3
      Fruits" and are common ingredients in Tibetan medicines. Prof. Omura, Y of NY
      Medical College evaluated these "3 Fruits" and found that one of them available
      as a "Haritaki," had the highest normal cell telomere increasing effect by
      optimal dose, with improvement of circulation all over the body, which in turn
      inhibits cancer activity. He considered Tibetan medicine to be the most advanced
      medicine in the world before the 19th Century with its well-organized systematic
      method as described by colorful Tibetan medical paintings by Sangye Gyamtso (1653
      1705 CE). During a typical diagnosis, the physician examines the patients'
      tongue, radial arteries for pulse beats by the index, middle, and ring fingers of
      both hands and the urine for features like color, vapor, and bubbles, etc.

PMID- 24909017
TI  - The early eugenics movement and emerging professional psychiatry: conceptual
      transfers and personal relationships between Germany and North America, 1880s to
      1930s.
AB  - French-Austrian psychiatrist Benedict Augustin Morel's (1809-1873) Traits des
      degenerescences physiques, intellectuelles et morales de l'espece humaine (1857)
      was fully dedicated to the social problem of "degeneration" and it became very
      attractive to German-speaking psychiatrists during the latter half of the 19th
      century. Auguste Forel (1848-1931) and Constantin von Monakow (1853-1930) in
      Zurich integrated Morel's approach and searched for the somatic and morphological
      alterations in the human brain; a perspective of research that Ernst Ruedin (1874
      1952) at Munich further prolonged into a thorough analysis of hereditary
      influences on mental health. This paper investigates the continuities and major
      differences within some early eugenic traditions of the emerging field of
      psychiatry in the German-speaking countries and North America.

PMID- 24909018
TI  - Eugenics and racial biology in Sweden and the USSR: contacts across the Baltic
      Sea.
AB  - The 1920s saw a significant exchange between eugenicists in Sweden and the young
      Soviet state. Sweden did not take part in World War I, and during the years
      following immediately upon the Versailles peace treaty, Swedish scholars came to
      serve as an intermediary link between, on the one hand, Soviet Russia and Weimar
      Germany, and, on the other hand, Western powers. Swedish eugenicists organized
      conferences, lecture tours, visits, scholarly exchanges, and transfers and
      translation of eugenic research. Herman Lundborg, the director of the world's
      first State Institute of Racial Biology, was an old-fashioned, deeply
      conservative, and anti-communist "scientific" racist, who somewhat paradoxically
      came to serve as something of a Western liaison for Soviet eugenicists. Whereas
      the contacts were disrupted in 1930, Swedish eugenicists had a lasting impact on
      Soviet physical anthropologists, who cited their works well into the 1970s, long
      after they had been discredited in Sweden.

PMID- 24909019
TI  - Eugenics and migration: a case study of Salvation Army literature about Canada
      and Britain, c.1890-1921.
AB  - The eugenics movement attracted a wide range of supporters. This article explores
      this theme with relation to literature about the charitable work of the Salvation
      Army in Britain and Canada c.1890-1921, with a focus upon the emigration scheme
      outlined in William Booth's book In Darkest England and the Way Out. These
      writings indicate the widespread dispersal of eugenic ideology, and demonstrate
      the flexibility with which these theories were interpreted in this period. It
      will be shown that the Salvation Army adopted elements of both hereditarian and
      environmentalist views regarding racial health. These arguments were unified by
      the claim that the work of the organization made a worthy contribution to public
      health, both in the present and in the future. This case study sheds new light
      upon the history of a prominent evangelical Christian organization and upon the
      development of the international eugenics movement.

PMID- 24909020
TI  - "A visitation of providence:" Public health and eugenic reform in the wake of the
      Halifax disaster.
AB  - The Halifax Explosion provided the opportunity for an "experiment in public
      health" that was meant not only to restore but also to improve the city and its
      population in the process. The restructuring that occurred during the restoration
      was influenced by pre-existing ideals and prejudices which were reflected in the
      goals of the newly formed committees in charge of the reconstruction. The primary
      emphasis on improvement as well as control was the result of existing regional
      concerns regarding the emigration of the province's most "desirable" stock, in
      the form of healthy, educated young men and women, to central Canada and the
      eastern United States. Public health reforms reflected the eugenic goal of
      improving the overall quality of the population through education, surveillance,
      and inspection, resorting finally to institutionalizing people who public health
      officials determined were genuinely deficient.

PMID- 24909021
TI  - "Our power to remodel civilization": the development of eugenic feminism in
      Alberta, 1909-1921.
AB  - In addition to being a prominent political figure in equal rights legislation,
      Emily Murphy was a vital contributor to programs which sought to improve the
      human race through forced sterilization. These negative aspects of this period in
      feminist history tend to be described as outside of the women's sphere,
      representing instead the patriarchal realm of men. However, both eugenics and the
      first-wave feminist ambitions for equal political rights were connected through
      an agrarian construction of "mothers of the race." As "mothers of the race,"
      women in Alberta were responsible for the physical and moral betterment of the
      nation, and were directly engaged in concepts of intelligent motherhood, healthy
      childhood, and an overarching moral philosophy that was politically driven.

PMID- 24909022
TI  - Eugenics in the community: gendered professions and eugenic sterilization in
      Alberta, 1928-1972.
AB  - Scholarship on Alberta's Sexual Sterilization Act (1928-1972) has focused on the
      high-level politics behind the legislation, its main administrative body, the
      Eugenics Board, and its legal legacy, overlooking the largely female-dominated
      professions that were responsible for operating the program outside of the
      provincial mental health institutions. This paper investigates the relationship
      between eugenics and the professions of teaching, public health nursing, and
      social work. It argues that the Canadian mental hygiene and eugenics movements,
      which were fundamentally connected, provided these professions with an
      opportunity to maintain and extend their professional authority.

PMID- 24909024
TI  - Contraception or eugenics? Sterilization and "mental retardation" in the 1970s
      and 1980s.
AB  - Nonconsensual sterilization is usually seen as the by-product of a classist and
      racist society; disability is ignored. This article examines the 1973
      sterilization of two young black girls from Alabama and other precedent-setting
      court cases involving the sterilization of "mentally retarded" white women to
      make disability more central to the historical analysis of sterilization. It
      analyzes the concept of mental retardation and the appeal of a surgical solution
      to birth control, assesses judicial deliberations over the "right to choose"
      contraceptive sterilization when the capacity to consent is in doubt, and
      reflects on the shadow of eugenics that hung over the sterilization debate in the
      1970s and 1980s.

PMID- 24909023
TI  - Sterilization and birth control in the shadow of eugenics: married, middle-class
      women in Alberta, 1930-1960s.
AB  - The history of eugenic sterilization connotes draconian images of coerced and
      involuntary procedures robbing men and women of their reproductive health. While
      eugenics programs often fit this characterization, there is another, smaller, and
      less obvious legacy of eugenics that arguably contributed to a more empowering
      image of reproductive health. Sexual sterilization surgeries as a form of
      contraception began to gather momentum alongside eugenics programs in the middle
      of the 20th century and experiences among prairie women serve as an illustrative
      example. Alberta maintained its eugenics program from 1929 to 1972 and engaged in
      thousands of eugenic sterilizations, but by the 1940s middle-class married women
      pressured their Albertan physicians to provide them with sterilization surgeries
      to control fertility, as a matter of choice. The multiple meanings and
      motivations behind this surgery introduced a moral quandary for physicians, which
      encourages medical historians to revisit the history of eugenics and its
      relationship to the contemporaneous birth control movement.

PMID- 24909025
TI  - Dr. William Feindel.

PMID- 24909026
TI  - [Berber Pas: 'Culture change in a profession takes time'].

PMID- 24909027
TI  - [Forensic veterinary medicine].

PMID- 24909028
TI  - [Legal use of birth jack is coming].

PMID- 24909029
TI  - [Selectively drying off according to the guideline].

PMID- 24909030
TI  - [Does your customer also suffer from a citizen-consumer paradox?].

PMID- 24909031
TI  - [Q&A Guidelines].

PMID- 24909032
TI  - [Trends from the GD-monitoring].

PMID- 24909033
TI  - [Essential thrombocythemia in a cat, associated with feline leukemia virus].

PMID- 24909034
TI  - [Practice techniques to operate on the claw joint and tendons in a valuable cow
      with infected claws].

PMID- 24909035
TI  - [Quality control for antibiotic sensitivity testing in 2013].

PMID- 24909036
TI  - [The use of bromide as antiepileptic agent in the dog].

PMID- 24909037
TI  - [The small letters].

PMID- 24909038
TI  - [Public health is the responsibility from everyone].

PMID- 24909039
TI  - ['Here comes all my knowledge together'].

PMID- 24909040
TI  - Psychosocial working conditions in today's workplaces: towards an increased
      specificity in risk assessment and management.

PMID- 24909041
TI  - Exposure to psychosocial factors at work and mental well-being in Europe.
AB  - BACKGROUND: Depression among workers is a major health concern and psychological
      work factors are considered important risk factors. OBJECTIVES: To investigate
      exposure to psychosocial work risk factors and prevalence of depressive symptoms
      in the European working population, and to identify the psychosocial work
      characteristics that predict them. METHODS: The study is a secondary data
      analysis based on a sample of 33,907 European employees from the last edition of
      the European Working Condition Survey (EWCS 2010). The relationship between the
      outcome variable (depressive symptoms) and the predictors (psychosocial work
      factors) was analyzed using a multi-stage Poisson model, estimating gender
      specific relative risks (RR) and 95 percent confidence intervals. RESULTS: After
      adjustment for individual and work characteristics, countries and other
      psychosocial factors, among men the RR of depressive symptoms was significantly
      increased for exposure to intermediate psychological demands and to high demands
      for hiding emotions, whereas high skill discretion, high support from colleagues,
      high support from managers, high job rewards and high job security significantly
      decreased the risk. Among women, high psychological demands and intermediate
      emotional demands significantly enhanced the risk of depressive symptoms while
      high decision authority, intermediate support from colleagues, high support from
      managers, high social climate, high job rewards and high job security protected
      against risk. CONCLUSIONS: A high prevalence of depressive symptoms was found in
      the EWCS 2010, although with wide variations between countries. Several
      psychosocial factors at work were identified as risk factors for depressive
      symptoms, even after adjusting for workplace co-exposures and other potential
      confounders.

PMID- 24909042
TI  - Emotional demands as a risk factor for mental distress among nurses.
AB  - BACKGROUND: Although it is widely acknowledged that in certain occupations
      emotional demands may be a critical phenomenon for workers' health, this has been
      traditionally taken for granted and their role in the stress process has not
      often been directly assessed. OBJECTIVES: To examine the relationship between
      emotional demands and mental distress, adjusting for the potential effect of
      common psychosocial factors (workload, job control, social support, role
      stressors, and poor relationships) and personal psychological factors (i.e.
      having been diagnosed with anxiety or depressive disorder). METHODS: A cross
      sectional study on a sample of nurses of the National Healthcare Service was
      carried out (N = 256, 81.3% women). The psychosocial factors considered were
      assessed by means of widely known and validated scales. The examined health
      outcome (i.e. mental distress) was operationalized by means of the General Health
      Questionnaire (12-item version). Covariates: gender, age, tenure and shiftwork.
      ANALYSES: a series of logistic regressions. RESULTS: Exposure to emotional
      demands was a risk factor for mental distress. The resulting risk was not altered
      when adjusting for other psychosocial and personal factors. In the final model
      emotional demands, workload and role stressors, in addition to having been
      diagnosed with anxiety or depressive disorder, were significant risk factors for
      nurses' mental distress. CONCLUSIONS: Emotional demands may substantially impact
      on nurses mental distress. These results give rise to concern in relation to work
      stress prevention in certain professions, given that emotional demands are not
      included in the most common psychosocial risk assessment tools currently
      available, which may then miss identifying an important precondition of work
      stress.

PMID- 24909043
TI  - Psychosocial risk among migrant workers: what we can learn from literature and
      field experiences.
AB  - BACKGROUND: Mental health problems are possible in migrant workers (MWs), who are
      mainly employed in dangerous jobs and face many barriers to prevention and care.
      OBJECTIVES: To outline current scientific evidence about psychosocial risk among
      MWs; to present data from clinical and field experiences. METHODS: Non-systematic
      literature review (PubMed, last 10 years); case series of 20 MWs, evaluated for
      mental and/or behavioural disorders at a public occupational health unit; applied
      field research, in enterprise contexts. RESULTS: A relatively low number of
      publications about psychosocial risk among MWs was found. Individual migrants may
      find the experience of migration to be stressful, with increased rates of
      depression and/or anxiety disorders. Data from clinical case series suggest that
      MWs from some ethnic groups, with a medium-high level of education, employed in
      metal or manufacturing industries, might have an increased risk of developing
      psychiatric disorders. Preliminary data from our field study seem to confirm that
      MWs, predominantly employed in unskilled/manual jobs and more prone to work
      overtime, tend to present higher prevalence of psychiatric disorders.
      CONCLUSIONS: There is a growing need to improve the scientific knowledge on
      migration, work, and mental health, as well as to promote workplace prevention of
      mental disorders in MWs. This can be achieved also by reducing structural
      barriers to mental wellbeing: in particular, occupational physicians should
      answer to MWs' mental health needs, contributing both to diagnosis and management
      of MWs' work-related psychiatric disorders.

PMID- 24909044
TI  - Context specificity in the assessment of psychosocial risk at work: an empirical
      study on Italian call centre workers.
AB  - BACKGROUND: Following EU requirements, in recent years standard procedures for
      the assessment of work-related stress have been developed in Italy. However,
      while such standardization has facilitated the spread and use of these
      procedures, it has brought a lack of specificity in risk assessment. OBJECTIVES:
      To exemplify a method for the assessment of work-related stress that was
      developed by the University of Milan to allow the definition of risk profiles
      tailored to the different organizational settings. METHODS: We examined risk
      factors for work-related stress in call centre operators employed by two separate
      Italian companies. At an early stage of the assessment procedure, we conducted a
      wide series of consultation and training activities that allowed the
      identification of context-specific risk factors and homogeneous groups, which
      fuelled the preparation of both the "objective" and the "subjective" evaluation
      instruments. RESULTS: Results obtained by means of the standardized "Effort
      Reward Imbalance Questionnaire" and "Job Content Questionnaire", interpreted in
      the light of consultations with key organizational figures and individual
      interviews with employees, have allowed the detection of different risk profiles
      and priorities for intervention at both the group and the organizational levels.
      CONCLUSIONS: Findings demonstrated the existence of both common and specific risk
      factors in the two companies, which would have remained undetected with the
      exclusive use of standardized approaches.

PMID- 24909045
TI  - Using an integrated approach to the assessment of the psychosocial work
      environment: the case of a major hospital in northern Italy.
AB  - BACKGROUND: In 2010, Italian regulatory guidelines have been issued consisting of
      a stepwise procedure for the assessment and management of work-related stress.
      However, research that empirically examines whether this procedure proves
      effective in accurately identifying critical psychosocial factors and informing
      risk management is scarce. OBJECTIVES: To examine the differential sensitivity of
      two approaches to risk assessment, the first based on objective instruments only,
      the second consisting of an integrated approach combining different methods and
      theoretical perspectives. METHODS: We examined a sample of 306 healthcare
      employees in a large-size hospital in northern Italy, using a series of tools,
      both quantitative (an observational checklist and the HSE-IT and MOHQ
      questionnaires) and qualitative (Focus Groups). Through instrument-specific
      reference values, we then compared risk profiles between different homogeneous
      groups within the institution. RESULTS: The psychosocial work environment
      resulted to be far more positive when adopting the first compared to the second
      approach to risk assessment. The latter approach was also more sensitive in
      detecting between-groups differences in risk profiles. Furthermore, the Focus
      Groups returned a more context-specific picture of the psychosocial work
      environment. Finally, going beyond the emphasis on negative working conditions
      inherent in the other quantitative instruments, the MOHQ allowed for also
      identifying health-promoting factors in need for improvement. CONCLUSIONS:
      Although more research is needed to confirm our findings, the present study
      suggests that using an integrated approach to assess the psychosocial work
      environment may be the most effective way to accurately identify risk factors and
      support the management process.

PMID- 24909046
TI  - Conclusions.

PMID- 24909047
TI  - [The assessment of biological risk in the manipulation of cells].

PMID- 24909048
TI  - [From the German example, possible compartmentalization of standardized
      procedures for the assessment of work-related stress in small- and medium-size
      enterprises (SMEs)].

PMID- 24909049
TI  - [Change of the name of the Italian Ergonomics Society to Italian Society of
      Ergonomics and Human Factors].

PMID- 24909050
TI  - Asbestos risk in archaeology.

PMID- 24909051
TI  - [Obituary. Prof. Nicolo Castellitto].

PMID- 24909052
TI  - Nitroglycerin patch for the treatment of chondrodermatitis nodularis helicis: a
      new therapeutic option.
AB  - Chondrodermatitis nodularis helicis (CNH) is an inflammatory process that affects
      the skin and cartilage of the ear. At present, there are many treatment options,
      although they are not always effective. Based on previous studies where
      nitroglycerin 2% gel was used, we propose the use of nitroglycerin patches. The
      purpose of this study was to evaluate the effectiveness of nitroglycerin patches
      in treating CNH. We performed a prospective study in 11 patients diagnosed with
      CNH treated with nitroglycerin patches 5 mg, 12 hours a day for 2 months. The
      therapeutic effectivity was determined by the improvement in the appearance and
      symptoms of the lesion. Seven of 11 patients (63.6%) had a complete response. One
      of 11 patients (9%) did not respond completely and surgical treatment was
      performed. Two of 11 patients (18.1%) stopped the treatment because of headache.
      One of 11 patients (9%) did not complete the treatment because the said patient
      forgot to apply the patch every night. Transdermal nitroglycerin has demonstrated
      efficacy in the treatment of the symptoms and lesional appearance of CNH
      noninvasive manner. The success rate is comparable with other published methods
      and the rate of adverse effects is acceptable. 

PMID- 24909054
TI  - On plasma cell longevity or brevity.
AB  - The seemingly long half-life of antibody-producing plasma cells demonstrated by
      antigen-binding (ELISA type of) assays as compared with the short-livedness of
      neutralizing and protective antibody-producing plasma cells is explained here by
      the heterogeneity and multiple crossreactive antibodies detected by ELISA-type
      assays. While DNP-specific B cell frequencies are about 10(-2) that of virus,
      serotype-specific B cell frequencies are about 10(-5)-10(-6). Therefore, the
      seemingly long-lived multiple low-affinity crossreactive antibody-producing
      plasma cells represent a collective of little if any biological or evolutionary
      relevance. The plasma cells producing high-affinity protective, neutralizing
      antibodies (>10(9) M(-1)) in mice are short-lived and therefore continued
      antibody production is dependent on antigen exposure from within (immune
      complexes and persistence of infections) or from without by epidemiologically
      circulating infectious agents, or by revaccinations. 

PMID- 24909055
TI  - Electrocatalytic and photocatalytic conversion of CO(2) to methanol using
      ruthenium complexes with internal pyridyl cocatalysts.
AB  - The ruthenium complexes [Ru(phen)2(ptpbalpha)](2+) (Rualpha) and
      [Ru(phen)2(ptpbbeta)](2+) (Rubeta), where phen =1,10-phenanthroline ; ptpbalpha =
      pyrido[2',3':5,6]pyrazino[2,3-f][1,10]phenanthroline; ptpbbeta =
      pyrido[3',4':5,6]pyrazino[2,3-f][1,10]phenanthroline, are shown as
      electrocatalysts and photocatalysts for CO2 reduction to formate, formaldehyde,
      and methanol. Photochemical activity of both complexes is lost in water but is
      retained in 1 M H2O in DMF. Controlled current electrolysis of a solution of
      Rubeta in CO2 saturated DMF:H2O (1 M) yields predominantly methanol over a 6 h
      period at ~ -0.60 V versus Ag/AgCl, with traces of formaldehyde. After this time,
      the potential jumped to -1.15 V producing both methanol and CO as products.
      Irradiation of Rubeta in a solution of DMF:H2O (1 M) containing 0.2 M TEA (as the
      sacrificial reductant) yields methanol, formaldehyde, and formate.
      Identifications of all of the relevant redox and protonated states of the
      respective complexes were obtained by a combination of voltammetry and
      differential reflectance measurements. Spectroelectrochemistry was particularly
      useful to probe the photochemical and electrochemical reduction mechanisms of
      both complexes as well as the complexes speciation in the absence and presence of
      CO2. 

PMID- 24909053
TI  - Multiple functions of hypoxia-regulated miR-210 in cancer.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post
      transcriptionally. miRNAs can be induced by a variety of stresses such as
      hypoxia, and are involved in diverse biological processes including
      differentiation, cell proliferation, cell death, and tumorigenesis. Hypoxia, a
      common feature of tumor microenvironment, can induce a number of miRNAs
      expression. miRNA-210 (miR-210) is one of the hypoxia-regulated-miRNAs, which has
      been investigated extensively in cancer. However, paradoxically opposing results
      were documented regarding whether it is an oncogene or a tumor suppressor, and
      whether it is a positive or negative prognostic biomarker. In the present review,
      we focus on the following investigations of miR-210: 1) its functions of as an
      oncogene, 2) its functions as a tumor suppressor, 3) its functions in
      mitochondrial metabolism, and finally, the diagnostic and prognostic value of miR
      210 in cancer researches. 

PMID- 24909056
TI  - Increased detection of gestational diabetes mellitus by using HbA1c screening in
      the first antenatal blood tests.

PMID- 24909057
TI  - Heritability of flight and resting metabolic rates in the Glanville fritillary
      butterfly.
AB  - Dispersal capacity is a key life-history trait especially in species inhabiting
      fragmented landscapes. Evolutionary models predict that, given sufficient
      heritable variation, dispersal rate responds to natural selection imposed by
      habitat loss and fragmentation. Here, we estimate phenotypic variance components
      and heritability of flight and resting metabolic rates (RMRs) in an ecological
      model species, the Glanville fritillary butterfly, in which flight metabolic rate
      (FMR) is known to correlate strongly with dispersal rate. We modelled a two
      generation pedigree with the animal model to distinguish additive genetic
      variance from maternal and common environmental effects. The results show that
      FMR is significantly heritable, with additive genetic variance accounting for
      about 40% of total phenotypic variance; thus, FMR has the potential to respond to
      selection on dispersal capacity. Maternal influences on flight metabolism were
      negligible. Heritability of flight metabolism was context dependent, as in
      stressful thermal conditions, environmentally induced variation dominated over
      additive genetic effects. There was no heritability in RMR, which was instead
      strongly influenced by maternal effects. This study contributes to a mechanistic
      understanding of the evolution of dispersal-related traits, a pressing question
      in view of the challenges posed to many species by changing climate and
      fragmentation of natural habitats. 

PMID- 24909059
TI  - Association between social determinants of health and functional dentition in 35
      year-old to 44-year-old Brazilian adults: a population-based analytical study.
AB  - OBJECTIVES: To verify the association between functional dentition and social
      determinants of health in 35-year-old to 44-year-old adults residing in the
      metropolitan municipalities of Minas Gerais, Brazil. METHODS: This cross
      sectional study assessed a sample of 850 adults obtained using a cluster sampling
      scheme. Five of 33 municipalities were randomly selected, followed by the random
      selection of census tracts and neighborhood blocks. Every household in the
      randomly selected blocks was visited and every resident adult was interviewed and
      examined by five previously calibrated researchers (kappainter , 0.8-0.9;
      kappaintra , 0.8-1.0) between May and December 2010. The condition of the dental
      crown was recorded using the World Health Organization (WHO) criteria, with the
      exception of the third molars. The dependent variable functional dentition was
      defined as the presence of 20 or more teeth in the mouth and obtained by counting
      the number of teeth lost due to any reason, followed by subtraction of this
      number from the total of 28 teeth. Independent variables were grouped, according
      to a theoretical model adapted from those proposed by Dahlgren and Whitehead and
      Petersen, into distal factors (contextual, socioeconomic, and housing
      conditions), intermediate factors (availability and use of oral health services),
      and proximal factors (lifestyle, risk behaviors, and demographic conditions). The
      association between functional dentition and the independent variables was
      investigated using simple and multiple Poisson regression with robust variance,
      which followed a modeling strategy in accordance with the hierarchy outlined by
      the theoretical model. The analyses were processed on SPSS 17.0. RESULTS: The
      average age of the participants was 39.4 +/- 3.2 years, and the average per
      capita monthly family income was US$214.52 +/- 261.11. Most adults presented
      functional dentition (80.6%; 95% CI: 77.3-83.5). Independently of marital status,
      age group and sex, the prevalence ratio (PR) of subjects with a per capita
      monthly family income >=US$168.54 was 1.09 (P = 0.048); the PR of adults with at
      least an undergraduate degree was 1.14 (P = 0.001), and the PR of the
      participants who most often used a dental service other than a public service
      supplementary healthcare plan or private service was 1.13 (P = 0.021). The
      prevalence of functional dentition was 17% higher among nonsmokers (P = 0.012)
      and 16% higher among those who used dental floss (P = 0.006). CONCLUSIONS:
      Income, education, type of dental service most often used, lifestyle, risk
      behaviors and demographic conditions are distal, intermediate and proximal social
      determinants of health associated with functional dentition in adults,
      demonstrating the need for public policies aimed to promoting oral health
      including intersectoral actions.

PMID- 24909058
TI  - Annexin A10 expression correlates with serrated pathway features in colorectal
      carcinoma with microsatellite instability.
AB  - Annexin A10 (ANXA10) has recently been identified as a marker of sessile serrated
      adenomas/polyps of the colorectum. Although the serrated neoplasia pathway is
      thought to be involved in the majority of microsatellite instability-high (MSI-H)
      sporadic colorectal carcinomas (CRCs), the clinicopathological implications of
      ANXA10 expression in CRC are unknown. Here, we evaluated ANXA10 expression status
      in 168 MSI-H CRCs by immunohistochemistry. Among 168 MSI-H CRCs, nuclear staining
      for ANXA10 in tumor cells revealed 28 cases (17%) with ANXA10-positive (ANXA10+)
      tumors. Most of the ANXA10+ tumors were located in the proximal colon (96%, p <
      0.001). The ANXA10+ phenotype in MSI-H CRC was significantly associated with
      female gender (68%, p = 0.016), CpG island methylator phenotype-high (CIMP-H)
      (68%, p < 0.001), MLH1 promoter hypermethylation (61%, p < 0.001), loss of MLH1
      expression (82%, p = 0.019), and wild-type KRAS status (96%, p = 0.023). Survival
      analysis revealed no prognostic significance of ANXA10 expression in MSI-H CRC.
      In conclusion, ANXA10+ MSI-H colon carcinomas are characterized by serrated
      pathway features, including proximal location, female predominance, and high
      frequencies of CIMP-H status and MLH1 methylation.

PMID- 24909060
TI  - Simultaneous overexpression of multidrug efflux pumps in Pseudomonas aeruginosa
      non-cystic fibrosis clinical isolates.
AB  - The purpose of this study was to examine expression and regulation of 6 multidrug
      efflux systems, including MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY, MexJK, and
      MexVW, in 13 non-cystic fibrosis (CF) clinical isolates of Pseudomonas
      aeruginosa. These isolates displayed a high level of resistance to many
      clinically important antibiotics. Some isolates simultaneously overexpressed up
      to 4 different Mex systems, as determined by quantitative real-time reverse
      transcription PCR. None of the isolates overexpressed MexCD-OprJ, and only 1
      isolate overproduced MexJK. All the isolates overexpressed MexXY, while
      overexpression of MexEF-OprN and MexVW was common. DNA sequencing analysis of
      regulatory genes showed that no clear correlation could be established among (i)
      the presence of mutations, (ii) the type of mutations, (iii) the expression level
      of the Mex systems, and (iv) resistance to antibiotic substrates. The results
      suggest that the concomitant overexpression of some Mex systems may superimpose
      their antimicrobial drug efflux capabilities, contributing to the multidrug
      resistance phenotype in the P. aeruginosa non-CF clinical isolates. The existence
      of uncharacterized regulators for the Mex systems was signified. 

PMID- 24909061
TI  - The role of hypoxia-inducible factors in organ donation and transplantation: the
      current perspective and future opportunities.
AB  - Hypoxia-inducible factors are the universal cellular oxygen-sensitive
      transcription factors that activate a number of hypoxia responsive genes, some of
      which are responsible for protective cellular functions. During organ donation,
      allografts are exposed to significant periods of hypoxia and ischemia. Exploiting
      this pathway during donor management and organ preservation could prevent and
      reduce allograft injury and improve the outcomes of organ transplantation. We
      review the evidence on this pathway in organ preservation, drawing on
      experimental studies on donor management and ischemia reperfusion injury focusing
      on kidney, liver, cardiac and lung transplantation. We review the major technical
      and experimental challenges in exploring this pathway and suggest potential
      future avenues for research. 

PMID- 24909062
TI  - Fluorescein angiography of aggressive posterior retinopathy of prematurity
      treated with intravitreal anti-VEGF in large preterm babies.

PMID- 24909063
TI  - Human filarial Wolbachia lipopeptide directly activates human neutrophils in
      vitro.
AB  - The host inflammatory response to the Onchocerca volvulus endosymbiont,
      Wolbachia, is a major contributing factor in the development of chronic pathology
      in humans (onchocerciasis/river blindness). Recently, the toll-like pattern
      recognition receptor motif of the major inflammatory ligands of filarial
      Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined
      in murine models of pathology, including mediation of neutrophil recruitment to
      the cornea. However, the extent to which human neutrophils can be activated in
      response to this Wolbachia pattern recognition motif is not known. Therefore, the
      responses of purified peripheral blood human neutrophils to a synthetic N
      terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan
      associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose
      dependent activation of healthy, human neutrophils that included gross
      morphological alterations and modulation of surface expressed integrins involved
      in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not
      chemokinesis of neutrophils, and secretion of the major neutrophil chemokine,
      interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced
      neutrophil survival by delay of apoptosis. These results indicate that the major
      inflammatory motif of filarial Wolbachia lipoproteins directly activates human
      neutrophils in vitro and promotes a molecular pathway by which human neutrophils
      are recruited to sites of Onchocerca parasitism.

PMID- 24909064
TI  - Premature newborns with fatal intrauterine herpes simplex virus-1 infection:
      first report of twins and review of the literature.
AB  - BACKGROUND: Neonates with blistering skin diseases are dermatologic emergencies.
      The pathologies involved can pose diagnostic difficulties and there exists a
      variety of potential life-threatening differential diagnoses. OBJECTIVE:
      description of the first case of intrauterine acquired herpes simplex virus (HSV)
      1 infection in twins. METHODS: We present the case of two premature bicordial
      biamniotic twins (27th week of gestation) whose intrauterine growth retardation,
      fetal anaemia and cardiotocography abnormalities led to a caesarean emergency
      delivery. RESULTS: Accurate medical history revealed a maternal febrile
      gingivostomatitis at the 23rd week of gestation, which was neglected by the
      treating gynaecologist. Respiratory distress was present at delivery and
      intubation was necessary in both children. The whole skin showed extensive
      erosions and ulcerations and the mucosa of the eyes and genitals was also
      involved. Intrauterine Herpes simplex virus (HSV) 1 infection was confirmed by
      immunohistochemistry of skin Tzanck smear (HSV 1 positive, HSV 2 negative), real
      time polymerase chain reaction of both serum and skin (HSV 1 positive; HSV 2
      negative) and maternal serology positive for HSV 1 IgM and IgG. Siblings were
      immediately treated with high-dose endovenous acyclovir. Anaemia thrombocytopenia
      and hepatorenal values markedly deteriorated and both developed consequential
      hepatorenal failure. The third day live supportive measures were terminated after
      parental informed consent and both siblings deceased shortly after on their
      mother's breast. DISCUSSION: Intrauterine HSV infection is rare and accounts only
      for 5% of neonatal HSV infections. Literature reports only 64 cases and 90% of
      those are related to HSV-2. Transplacental viral transmission is highest during
      the first 20 weeks of gestation and has been observed in pregnant women with
      disseminated HSV infection. Mortality and morbidity of intrauterine herpetic
      infection are extremely high. CONCLUSION: Despite transplacental HSV transmission
      remains a rare event, the potential devastating outcome justifies immediate
      adequate antiviral treatment in a pregnant woman affected by primary HSV
      infection.

PMID- 24909065
TI  - Antibacterial effect of coffee: calcium concentration in a culture containing
      teeth/biofilm exposed to Coffea Canephora aqueous extract.
AB  - This study determined the changes of calcium concentration in a medium containing
      teeth/biofilm exposed to Coffea canephora extract (CCE). Enamel fragments were
      randomly fixed into two 24-well polystyrene plates containing BHI. Pooled human
      saliva was added to form biofilm on fragments. Specimens were divided into
      treatment groups (G, n = 8 per group) and treated with 50 MUl daily for 1 min per
      week, as follows: G1, 20% CCE; G2, Milli-Q water (negative control); G3,
      antibiotic (positive control). Six fragments represented the blank control (G4).
      The calcium content was observed at baseline, 4 and 7 days of treatment by atomic
      absorption spectrophotometry. Cross-sectional hardness of enamel was a
      demineralization indicator. Calcium increased in the medium after 4 and 7 days of
      treatment in G1 (3.80 +/- 1.3 mg l(-1) and 4.93 +/- 2.1 mg l(-1) , respectively)
      and G3 (4th day = 5.7 +/- 1.8 mg l(-1) ; 7th day = 6.7 +/- 3.5 mg l(-1) ) (P >
      0.05). Calcium from G2 decreased after 7 days, which was different from G3 (P <
      0.05). The lower calcium content, at the end of the experiment, was represented
      by G4, 2.16 +/- 0.2 mg l(-1) . The increase in calcium after treatment with CCE
      is probably due to its antibacterial effect, which caused the bacterial lysis and
      consequent release of calcium in the medium. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study revealed an inhibitory action of Coffea canephora against
      dental biofilm. This coffee species caused bacterial lysis and consequent release
      of calcium into the medium. Furthermore, the advantage of coffee as an
      antibacterial beverage is that it is consumed in a concentrated form (6-10%) as
      opposed to various medicinal infusions that have shown such effect in vitro and
      are usually consumed at 1-2%. Therefore, a light roasted C. canephora aqueous
      extract can be considered as a potential anticariogenic substance.

PMID- 24909066
TI  - Editorial comment from Dr Urakami to impact of obesity on the predictive accuracy
      of prostate-specific antigen density and prostate-specific antigen in native
      Korean men undergoing prostate biopsy.

PMID- 24909067
TI  - Pharmacovigilance in oncology: evaluation of current practice and future
      perspectives.
AB  - RATIONALE, AIMS AND OBJECTIVES: Pharmacovigilance (PV), or drug safety
      monitoring, aims to improve patient safety through the detection and management
      of drug-related adverse reactions. It is implemented both by spontaneous
      reporting of adverse drug reactions (ADRs) and by careful detection of signals
      suggestive of drug toxicity. PV is an important clinical topic in clinical
      practice and pharmacotherapy, assuring the maintenance of a safe risk/benefit
      ratio throughout the commercial life cycle of a drug. METHODS: We conducted a
      structured literature search on PubMed, Scopus, Cinahl and the Cochrane Library.
      We also performed manual searches in international databases of ADR individual
      reports to outline a structured profile on the topic. Our goal was to review key
      elements that affect safety monitoring of cancer drugs and their appropriate use,
      highlighting the strengths and weaknesses of PV in oncology. RESULTS: This paper
      provides an understanding of the methodologies used by PV in current clinical
      practice and particularly in cancer drug therapy; a focus upon reporting of ADRs
      by health professionals and patients; and a focus upon methods used by PV to
      detect new signals of risk/harm related to medicines utilization. CONCLUSION: To
      our knowledge, few articles focus upon the importance of PV and post-marketing
      surveillance of cancer drug therapies. Structured management of spontaneous
      reports of ADRs and data collection is essential to monitoring the safe use of
      drugs in this field in which pharmacotherapy is affected by high incidence of
      drug-related complications and by a narrow benefit/risk ratio.

PMID- 24909068
TI  - Emerging role of cystic fibrosis transmembrane conductance regulator as an
      epigenetic regulator: linking environmental cues to microRNAs.
AB  - Although microRNAs (miRNAs) have been recognized as one of the important
      epigenetic mechanisms that regulate gene expression in response to changes in the
      environment, the links between environmental cues and changes in miRNAs remain
      largely unknown. Localized to the cell membrane and recognized as an anion
      channel, the cystic fibrosis transmembrane conductance regulator (CFTR) has
      recently been shown to mediate important signalling pathways leading to
      activation of miRNAs. This brief review summarizes the related findings and
      discusses the emerging role of CFTR as an epigenetic regulator, possibly involved
      in a wide spectrum of physiological and pathological processes. 

PMID- 24909069
TI  - Similarities and differences in the clinical features between cardia varices and
      esophageal varices.
AB  - BACKGROUND AND AIM: Little is known about the clinical features of cardia varices
      (CV). The aim was to examine the background, bleeding risk, and post-treatment
      outcomes of CV in patients with portal hypertension. METHODS: The subjects of
      this retrospective study were 277 patients (179 males, 98 females, 62.9 +/- 11.5
      years) with esophageal varices (EV). In patients with CV, there were 65 bleeders,
      and 95 patients received endoscopic treatment for primary or secondary
      prophylaxis. RESULTS: There were 147 patients with CV (53.1%). The higher grade
      of EV (P < 0.01) and the lower grade of gastric fundal varices (FV) (P = 0.046)
      were significant factors for the presence of CV. Significant risk factors for
      bleeding were: the higher grade of EV (P < 0.01), red sign on EV (P < 0.01),
      lower albumin (P = 0.01), and Child-Pugh B/C (P < 0.01) for EV and red sign on CV
      (P < 0.01) and use of non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin (P <
      0.01) for CV. All CV disappeared by sclerotherapy combined with argon plasma
      coagulation or band ligation, and 20 patients (21.1%) in EV and 18 patients
      (18.9%) in CV had recurrences during the median observation period of 19.4
      months. There was no significant difference in the cumulative survival rate
      between non-bleeders, bleeders from EV, and those from CV. CONCLUSIONS: The CV
      were closely associated with advanced grade of EV and less-advanced grade of FV.
      Further, usage of NSAIDs/aspirin and red sign were significantly related to the
      bleeding from CV, suggesting the need for careful management.

PMID- 24909070
TI  - PCR amplification and DNA sequence identification of an unusual morphological
      form of Demodex cati in a cat.
AB  - BACKGROUND: Molecular characterization of Demodex mites is being used to identify
      mite species in dogs. This technique is now being applied to cat Demodex species,
      allowing for better characterization of the mites. HYPOTHESIS/OBJECTIVES:
      Molecular diagnostics will clarify the existence of diverse Demodex mites
      identified morphologically. ANIMALS: A cat with generalized demodicosis secondary
      to chronic steroid treatment for erythroid dysplasia. METHODS: Skin scrapings
      demonstrated large numbers of follicular mites consistent with Demodex cati as
      well as a morphologically different Demodex mite with a blunted abdomen. The 16S
      rRNA DNA was amplified by PCR, sequenced and compared with available Demodex
      sequences, including Demodex cati, Demodex gatoi and an unnamed Demodex sp.
      RESULTS: A single PCR product was obtained, the DNA sequence of which was an
      exact match with D. cati. CONCLUSIONS AND CLINICAL IMPORTANCE: The shorter
      unnamed mite was not a different species in this case, but a different
      morphological form of D. cati. This report demonstrates the utility of molecular
      diagnostics to clarify the identity of mites that differ morphologically.

PMID- 24909071
TI  - 5HT3 receptor antagonist (ondansetron) reverses depressive behavior evoked by
      chronic unpredictable stress in mice: modulation of hypothalamic-pituitary
      adrenocortical and brain serotonergic system.
AB  - Chronic stress is one of the major causes of depression, associated with
      behavioral and biochemical impairments. 5HT3 receptor antagonists (such as
      ondansetron) have shown alleviation of depressive symptomology in preclinical and
      in few clinical studies. However, their effects in chronic stress-induced
      depressive behavior and the underlying mechanism(s) are yet to be known. In the
      present study, the effects of a 5HT3 receptor antagonist, ondansetron were
      evaluated in chronic unpredictable stress (CUS)-evoked depressive behavior. In
      addition, the possible mechanism was determined by measuring plasma
      corticosterone (CORT) as a marker of hypothalamic-pituitary-adrenocortical (HPA)
      axis activity and serotonin levels in the discrete brain regions. Mice were
      subjected to a battery of unpredictable stressors for 28 days. Ondansetron (0.05,
      0.1 and 1mg/kg, p.o.) and fluoxetine (10mg/kg, p.o.) were administered during the
      last 14 days (day 15-28th) of CUS testing paradigm. The results showed that the 4
      week CUS produced significant depressive behavior in mice, which included
      increased despair effects in forced swim test (FST) and reward-related deficits
      in sucrose preference test. Biochemical assays demonstrated a significant
      increase in percentage of plasma CORT and decrease in percentage of serotonin
      levels in the discrete brain regions of CUS mice. Chronic ondansetron treatment,
      similar to that of positive control fluoxetine, significantly reversed despair
      effects in FST and reward-related deficits in sucrose preference test. In
      addition, ondansetron and fluoxetine treatments significantly increased
      percentage of serotonin levels in the measured brain regions and attenuated HPA
      axis hyperactivity, as evidenced by low percentage of plasma CORT levels in CUS
      mice. These findings indicate the potential role of ondansetron (a 5HT3 receptor
      antagonist) in reversing CUS-induced depressive behavior, which is possibly
      mediated by its modulating effects on the HPA-axis and serotonergic system.
      Further, the study represents that 5HT3 receptor antagonists can be a potential
      therapeutic candidate for stress-related depressive disorders.

PMID- 24909072
TI  - Lipoxin A4 methyl ester ameliorates cognitive deficits induced by chronic
      cerebral hypoperfusion through activating ERK/Nrf2 signaling pathway in rats.
AB  - Lipoxin A4 (LXA4) is known for its powerful anti-inflammatory function. Current
      studies in vitro suggest that LXA4 possesses novel antioxidant effect. The aim of
      this study is to examine whether Lipoxin A4 methyl ester (LXA4 ME) has
      neuroprotective effects against chronic cerebral hypoperfusion, and if so,
      whether the effects of LXA4 ME are associated with its potential antioxidant
      property. Adult male Sprague-Dawley rats were subjected to permanent bilateral
      common carotid artery occlusion (BCCAO) and randomly assigned into four groups:
      sham (sham-operated) group, vehicle (BCCAO+normal saline) group, LXA4 ME10
      (BCCAO+LXA4 ME 10 ng per day) group and LXA4 ME100 (BCCAO+LXA4 ME 100 ng per day)
      group. LXA4 ME was administered through intracerebroventricular injection for 2
      consecutive weeks. LXA4 ME significantly alleviated spatial learning and memory
      impairments, as assessed by Morris water maze and inhibited the loss of neurons
      in the CA1 region of the hippocampus. Biochemically, LXA4 ME phosphorylated
      extracellular signal regulated kinase (ERK) 1/2 and enhanced nuclear factor
      erythroid 2-related factor 2 (Nrf2) expression and its nuclear translocation, as
      well as NAD(P)H: quinone oxidoreductase 1 (NQO1) expression. LXA4 ME reduced
      lipid peroxidative production in the hippocampus, as measured by
      immunohistochemical staining for 4-Hydroxynonenal (4-HNE). In addition, LXA4 ME
      significantly elevated the ratio of Bcl-2/Bax and decreased cleaved caspase-3
      expression in the hippocampus. Therefore, these data suggest that LXA4 ME exerts
      beneficial effects on the cognitive impairment induced by chronic cerebral
      hypoperfusion through attenuating oxidative injury and reducing neuronal
      apoptosis in the hippocampus, which is most likely associated with the activation
      of ERK/Nrf2 signaling pathway.

PMID- 24909073
TI  - Birth experience of women conceiving with assisted reproduction: a prospective
      multicenter study.
AB  - OBJECTIVE: To determine how infertility and subsequent assisted reproductive
      treatment (ART) affect a woman's childbirth experience. DESIGN: Prospective
      multicenter case-control study. SETTING: We recruited women pregnant with a
      singleton fetus after either ART (n = 324) or spontaneous conception (n = 304)
      from five infertility clinics and one university maternity clinic in Finland.
      METHODS: We studied their childbirth experience with the Delivery Satisfaction
      Scale. We compared how psychosocial and obstetric factors affected satisfaction
      and dissatisfaction with childbirth between and within the ART and the control
      group. Logistic regression was then used to analyse the most important
      contributors to the experienced dissatisfaction. RESULTS: Dissatisfaction with
      childbirth was as common in the ART group (11%) as in the control (10%) group. In
      the ART group, the women's education level, cesarean section (CS) and their
      partner's absence from the delivery were associated with dissatisfaction. In the
      control group, significant factors for dissatisfaction were nulliparity, severe
      pregnancy-related anxiety, emergency CS, recalled intense pain and the partner's
      absence from the delivery. According to adjusted logistic regression analysis of
      the whole sample, the independent risk factors were elective CS [odds ratio (OR)
      5.7; 95% confidence interval (CI) 2.2-14.1] and emergency CS (OR 2.9; 95% CI 1.3
      6.5), recalled intense pain (OR 6.8; 95% CI 3.3-16.2) and the partner's absence
      from the delivery (OR 2.7; 95% CI 1.1-7.3). CONCLUSION: ART is not a risk factor
      for dissatisfaction with childbirth by itself. However, the contributors to an
      unsatisfactory childbirth differ partly between women conceiving with ART and
      those conceiving spontaneously.

PMID- 24909074
TI  - Relation between Spongy Bone Density in the Maxilla and Skeletal Bone Density.
AB  - BACKGROUND AND PURPOSE: Osteoporosis is a disease affecting more than 300 million
      people worldwide and is responsible for numerous medical complications. This
      study aimed to investigate the relation between skeletal and maxillary bone
      density. MATERIALS AND METHODS: Seventy-three patients were recruited and divided
      between group A (osteoporosis), group B (healthy, control), and group C
      (osteopenia) on the basis of a dual-energy x-ray absorptiomery (DXA) scan. These
      patients also received a CT scan on which bone density measurements were
      performed at five sites: maxilla midline, retromolar tuberosities, incisor,
      premolars, and molar regions. RESULTS: The bone density was lower in osteoporotic
      patients compared with the control patients. The bone mineral density (BMD) of
      the tuberosities showed the strongest correlations with the BMD of the hip and
      the spine (respectively, r = 0.50 and r = 0.61). The midline region showed
      moderate correlations with the hip (r = 0.47) and the spine (r = 0.46). For
      potential implant sites, the correlations with the BMD of the hip and spine were,
      however, small to insignificant. Based on measurements of bone density of the
      maxilla, it was possible to predict if the patient was osteoporotic or not with a
      sensitivity of 65% and a specificity of 83%. CONCLUSIONS: The maxillary bone
      density of subjects with osteoporosis is significantly lower than that of healthy
      patients. Moreover, there is a direct correlation between the density of the
      skeleton and the density of some sites of the maxilla. Using measurements of
      maxillary bone density in order to predict skeletal bone density might be a
      useful tool for the screening of osteoporosis.

PMID- 24909075
TI  - Validity of a measure to assess healthy eating and physical activity policies and
      practices in Australian childcare services.
AB  - BACKGROUND: Childcare services represent a valuable obesity prevention
      opportunity, providing access to a large portion of children at a vital point in
      their development. Few rigorously validated measures exist to measure healthy
      eating and physical activity policies and practices in this setting, and no such
      measures exist that are specific to the childcare setting in Australia. METHODS:
      This was a cross sectional study, comparing two measures (pen and paper survey
      and observation) of healthy eating and physical activity policies and practices
      in childcare services. Research assistants attended consenting childcare services
      (n = 42) across the Hunter region of New South Wales, Australia and observed
      practices for one day. Nominated Supervisors and Room Leaders of the service also
      completed a pen and paper survey during the day of observation. Kappa statistics
      and proportion agreement were calculated for a total of 43 items relating to
      healthy eating and physical activity policies and practices. RESULTS: Agreement
      ranged from 38%-100%. Fifty one percent of items showed agreement of greater than
      or equal to 80%. Items assessing the frequency with which staff joined in active
      play with children reported the lowest percent agreement, while items assessing
      availability of beverages such as juice, milk and cordial, as well as the
      provision of foods such as popcorn, pretzels and sweet biscuits, reported the
      highest percent agreement. Kappa scores ranged from -0.06 (poor agreement) to 1
      (perfect agreement). Of the 43 items assessed, 27 were found to have moderate or
      greater agreement. CONCLUSIONS: The study found that Nominated Supervisors and
      Room Leaders were able to accurately report on a number of healthy eating and
      physical activity policies and practices. Items assessing healthy eating
      practices tended to have higher kappa scores than those assessing physical
      activity related policies or practices. The tool represents a useful instrument
      for public health researchers and policy makers working in this setting.

PMID- 24909076
TI  - Evaluation of a novel Dot-ELISA assay utilizing a recombinant protein for the
      effective diagnosis of Taenia pisiformis larval infections.
AB  - Cysticercosis, caused by the larvae of Taenia pisiformis, is a common disease in
      domestic breeds of the rabbit Oryctolagus cuniculus that results in economic
      losses. At present, there is no convenient and effective method for the rapid
      detection of T. pisiformis larvae. Here, we developed and tested the efficacy of
      a Dot-ELISA assay for the diagnosis of T. pisiformis larval infections in
      rabbits, based on the expression of the recombinant fusion protein (rTp1) from
      the Tp1 gene. Rapid amplification of cDNA ends (RACE) was used to amplify the 3'
      ends of the Tp1 gene, based on the unigene similar to Ts1 gene (EU009656.1) which
      comes from transcriptome sequencing of T. pisiformis. The Tp1 gene was
      successfully amplified, cloned and expressed in BL21 (DE3). Western blot analysis
      revealed that the recombinant Tp1 protein is specifically recognized by rabbit T.
      pisiformis cysticercosis antisera. This purified recombinant fusion protein,
      rTp1, was probed by Dot-ELISA with sera from rabbits infected with T. pisiformis
      larvae and with other parasitic infections. Results showed that this Dot-ELISA
      assay had both high sensitivity (92.9-97.6%) and specificity (95.2-98.4%) to
      detect T. pisiformis larval infections. We also found very low levels of cross
      reaction with other parasitic infections. This study has revealed that our novel
      Dot-ELISA assay utilizing the recombinant fusion protein, rTp1, has a strong
      potential for the effective diagnosis of T. pisiformis infections in rabbits. 

PMID- 24909077
TI  - Prevalence and molecular typing of Cryptosporidium in dairy cattle in England and
      Wales and examination of potential on-farm transmission routes.
AB  - An average of 70 samples were collected from 80 dairy farms in England and Wales,
      from cattle, co-grazed sheep, wildlife and farm wastes, to investigate
      prevalence, potential sources and transmission routes of Cryptosporidium. At
      least one positive sample was detected on 74 of the farms (92.5%) by IFAT
      microscopy. The prevalence in cattle was 10.2% (95% CI 9.4-11.1%), with greater
      prevalences detected in calf samples, especially from those under 1 month
      (45.1%). Young calves were also more likely to be shedding Cryptosporidium parvum
      and larger concentrations of oocysts, whereas older calves and adult cattle were
      more likely to be shedding Cryptosporidium bovis and Cryptosporidium andersoni,
      respectively. The C. parvum subtypes detected were predominantly from types
      commonly identified in UK cattle (67% were either IIaA15G2R1 or IIaA17G1R1). A
      novel subtype, IIaA17G1R2, was identified from one cattle sample. The prevalence
      in co-grazed sheep was low (4%). Birds and rodents may represent significant
      reservoirs of Cryptosporidium due to high prevalence, large oocyst
      concentrations, and the detection of a C. parvum subtype known to be present in
      human populations, identified in samples from these wildlife. Cryptosporidium
      were detected in dirty water and manure, and also from pasture samples where
      slurry had been spread. On 64% of the farms, identical Cryptosporidium species
      were detected (mainly C. parvum or C. bovis) from different cattle groups on the
      farms, although no direct or indirect contact between the groups were recorded,
      apart from sharing staff. The same Cryptosporidium species were found in cattle,
      farm wastes and bird samples on the same farms, but rarely, or not at all,
      present in sheep or rodent samples. The matching of species/subtypes was also
      related to the proximity of the different sample sources which may indicate a
      potential transmission route. 

PMID- 24909078
TI  - Biosynthesis of steroidal alkaloids in Solanaceae plants: incorporation of 3beta
      hydroxycholest-5-en-26-al into tomatine with tomato seedlings.
AB  - The C-26 amino group of tomatine, a representative Solanaceae steroidal alkaloid,
      is introduced in an early step of its biosynthesis from cholesterol. We recently
      proposed a transamination mechanism for the C-26 amination as opposed to the
      previously proposed mechanism involving a nitrogen nucleophilic displacement. In
      the present study, a deuterium labeled C-26 aldehyde, (24,24,27,27,27-(2)H5)
      3beta-hydroxycholest-5-en-26-al, was synthesized and fed to a tomato (Solanum
      lycopersicum) seedling. LC-MS analysis of the biosynthesized tomatine indicated
      that the labeled aldehyde was incorporated into tomatine. The finding strongly
      supports the intermediacy of the aldehyde and the transamination mechanism during
      C-26 amination. 

PMID- 24909080
TI  - Modulation of binding properties of amphiphilic DNA containing multiple dodecyl
      phosphotriester linkages to lipid bilayer membrane.
AB  - DNA is a promising functional molecule to modify and design lipid membrane
      functions. In order to use DNA in a hydrophilic-hydrophobic interface including
      lipid membrane, we have developed an amphiphilic DNA having dodecyl
      phosphotriester linkages (dod-DNA). Herein, we report the binding of a series of
      amphiphilic dod-DNAs to the lipid bilayer membrane. Surface plasmon resonance
      (SPR) assay and fluorescent microscopy showed that dod-DNA having three dodecyl
      groups at each end strongly bound to lipid membrane due to the slow dissociation
      rate and the dod-DNA can be used as a linear template for molecular arrangement
      on the membrane surface. 

PMID- 24909079
TI  - Scaffold-switching: an exploration of 5,6-fused bicyclic heteroaromatics systems
      to afford antituberculosis activity akin to the imidazo[1,2-a]pyridine-3
      carboxylates.
AB  - A set of 5,6-fused bicyclic heteroaromatic scaffolds were investigated for their
      in vitro anti-tubercular activity versus replicating and non-replicating strains
      of Mycobacterium tuberculosis (Mtb) in an attempt to find an alternative scaffold
      to the imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidines that were previously
      shown to have potent activity against replicating and drug resistant Mtb. The
      five new bicyclic heteroaromatic scaffolds explored in this study include a 2,6
      dimethylimidazo[1,2-b]pyridazine-3-carboxamide (7), a 2,6-dimethyl-1H-indole-3
      carboxamide (8), a 6-methyl-1H-indazole-3-carboxamide (9), a 7-methyl
      [1,2,4]triazolo[4,3-a]pyridine-3-carboxamide (10), and a 5,7-dimethyl
      [1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide (11). Additionally, imidazo[1,2
      a]pyridines isomers (2 and 12) and a homologous imidazo[1,2-a]pyrimidine isomer
      (6) were prepared and compared. Compounds 2 and 6 were found to be the most
      potent against H37Rv Mtb (MIC's of 0.1 MUM and 1.3 MUM) and were inactive (MIC
      >128 MUM) against Staphylococcus aureus, Escherichia coli and Candida albicans.
      Against other non-tubercular mycobacteria strains, compounds 2 and 6 had activity
      against Mycobacterium avium (16 and 122 MUM, respectively), Mycobacterium
      kansasii (4 and 19 MUM, respectively), Mycobacterium bovis BCG (1 and 8 MUM,
      respectively) while all the other scaffolds were inactive (>128 MUM).

PMID- 24909081
TI  - Synthesis of new heterocyclic lupeol derivatives as nitric oxide and pro
      inflammatory cytokine inhibitors.
AB  - A series of heterocyclic derivatives including indoles, pyrazines along with
      oximes and esters were synthesized from lupeol and evaluated for anti
      inflammatory activity through inhibition of lipopolysaccharide (LPS) induced
      nitric oxide (NO) production in RAW 264.7 and J774A.1 cells. All the synthesized
      molecules of lupeol were found to be more active in inhibiting NO production with
      an IC50 of 18.4-48.7 MUM in both the cell lines when compared to the specific
      nitric oxide synthase (NOS) inhibitor, L-NAME (IC50=69.21 and 73.18 MUM on RAW
      264.7 and J774A.1 cells, respectively). The halogen substitution at phenyl ring
      of indole moiety leads to potent inhibition of NO production with half maximal
      concentration ranging from 18.4 to 41.7 MUM. Furthermore, alkyl (11, 12) and p
      bromo/iodo (15, 16) substituted compounds at a concentration of 20 MUg/mL
      exhibited mild inhibition (29-42%) of LPS-induced tumor necrosis factor alpha
      (TNF-alpha) and weak inhibition (10-22%) towards interleukin 1-beta (IL-1beta)
      production in both the cell lines. All the derivatives were found to be non
      cytotoxic when tested at their IC50 (MUM). These findings suggest that the
      derivatives of lupeol could be a lead to potent inhibitors of NO.

PMID- 24909082
TI  - Synthesis and characterization of novel 1,2-oxazine-based small molecules that
      targets acetylcholinesterase.
AB  - Thirteen 2-oxazine-based small molecules were synthesized targeting 5
      lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the
      newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in
      lower micro molar concentration. Among the tested compounds, the most active
      compound, 2-[(2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3
      yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5
      LOX and AChE with an IC50 values of 1.88, and 2.5 MUM, respectively. Further, the
      in silico molecular docking studies revealed that the compound 2a bound to the
      catalytic domain of AChE strongly with a highest CDOCKER score of -1.18 kcal/mol
      when compared to other compounds of the same series. Additionally, 2a showed a
      good lipophilicity (logP=2.66), suggesting a potential ability to penetrate the
      blood-brain-barrier. These initial pharmacological data revealed that the
      compound 2a could serve as a drug-seed in developing anti-Alzheimer's agents.

PMID- 24909083
TI  - Rational design of the first difluorostatone-based PfSUB1 inhibitors.
AB  - The etiological agent of the most dangerous form of malaria, Plasmodium
      falciparum, has developed resistance or reduced sensitivity to the majority of
      the drugs available to treat this deadly disease. Innovative antimalarial
      therapies are therefore urgently required. P. falciparum serine protease
      subtilisin-like protease 1 (PfSUB1) has been identified as a key enzyme for
      merozoite egress from red blood cells and invasion. We present herein the
      rational design, synthesis, and biological evaluation of novel and potent
      difluorostatone-based inhibitors. Our bioinformatic-driven studies resulted in
      the identification of compounds 1a, b as potent and selective PfSUB1 inhibitors.
      The enzyme/inhibitor interaction pattern herein proposed will pave the way to the
      future optimization of this class of promising enzyme inhibitors. 

PMID- 24909084
TI  - Diabetes in primary care: back to basics.

PMID- 24909085
TI  - Diabetes management in primary care.

PMID- 24909086
TI  - Dual reporting of hemoglobin A1C in the Canadian Journal of Diabetes.

PMID- 24909087
TI  - Validation of the step test and exercise prescription tool for adults.
AB  - OBJECTIVE: Canadian clinical practice guidelines for the management of diabetes
      highlight the value of physical activity for improving clinical markers and risk
      factors for diabetes. The use of tools like the Step Test and Exercise
      Prescription (STEP) in clinical practice facilitates chronic disease management
      and prevention through the promotion of healthy physical activity. The validity
      and reliability of STEP has been established previously for use with adults 65 to
      85 years of age. The purpose of this study was to test the validity of the
      prediction equation for VO2max from the STEP tool for use with adults older than
      65 years. METHODS: Forty participants completed both the predictive self-paced
      VO2max stepping protocol from the STEP tool, and a maximal graded exercise
      treadmill test with breath-by-breath analysis of expired gases. Tests were
      completed in random order, and participants rested between tests until blood
      pressure returned to baseline. RESULTS: The average age of the sample was 43+/-14
      years. There was a strong relationship between predicted VO2max from STEP and
      direct measures of VO2max from the maximal treadmill test in the present study
      (r=.78, p<0.001). Bland-Altman analysis demonstrated statistical agreement
      between tests, although there was systematic overestimation of 6.4 mL/kg/min.
      CONCLUSIONS: STEP is an evidence-based cardiorespiratory fitness assessment and
      exercise prescription tool appropriate for use by various health professionals in
      clinical practice. The prediction equation for VO2max from the STEP tool is valid
      for use with adults 18 to 85 years of age. However, more research is warranted to
      explore age corrections to the prediction algorithm among younger adults.

PMID- 24909088
TI  - The relationship between primary care models and processes of diabetes care in
      Ontario.
AB  - This study examined the association between Ontario's differing primary care
      models and receipt of recommended testing for people with diabetes. We analyzed
      available administrative data for 757 928 people with diabetes aged 40 years and
      older. We assigned them to a primary care physician and assessed whether they had
      received 3 key monitoring tests between 2006 and 2008. We used multivariable
      generalized estimating equation models to test the associations among various
      primary care models and receipt of recommended testing. Ontarians with diabetes
      who were enrolled in a non-team blended capitation model (OR 1.18, 95% CI 1.09 to
      1.27) and those enrolled in a team-based blended capitation model (OR 1.20, 95%
      CI 1.13 to 1.28) were more likely than those enrolled in a blended fee-for
      service model to receive the optimal number of 3 recommended monitoring tests.
      Patients who were not enrolled in any model and who were assigned to a
      traditional fee-for-service physician were least likely to receive optimal
      monitoring compared to those enrolled in a blended fee-for-service model (OR
      0.60, 95% CI 0.57 to 0.62). The biggest gap in diabetes care was for patients not
      enrolled in any primary care model. Research and policy work is needed to
      understand and reduce this care gap, especially which provider and patient-level
      factors are involved. Options may include intensive outreach to patients,
      knowledge translation to physicians, encouraging enrollment and efforts to remove
      barriers to care. 

PMID- 24909089
TI  - Utilization of Diabetes Education Centres in Ontario by people without diabetes.
AB  - OBJECTIVE: The aim of this study was to describe the utilization of diabetes
      education centres by people not diagnosed with diabetes mellitus in real-world
      clinical care in Ontario. METHODS: Using population-level health administrative
      databases and registries, all people in Ontario, Canada, who attended a diabetes
      self-management education centre in 2006 were identified. The proportion of
      attendees without diagnosed diabetes at the time of their visit was determined,
      they were stratified by centre and health region, and their utilization of
      diabetes education centres was characterized. They were then followed up until
      2010 for incident diabetes. RESULTS: Of 117,660 adults attending a diabetes
      education centre, 19,920 (16.9%) did not have diagnosed diabetes. There was a
      marked variation in the proportion of attendees without diagnosed diabetes
      between health regions and between individual centres. More attendees did not
      have diagnosed diabetes at centres based in community health centres (47.5%) or
      First Nations communities (22.1%) than those based in hospitals (13.9%) or other
      community settings (13.0%). Only 2741 attendees (13.8%) without diabetes attended
      group education classes; most attended individual counselling sessions. Diabetes
      incidence during follow up was 11.2 cases per 100 person years. CONCLUSIONS: One
      in 6 people receiving care at a diabetes education centre in Ontario did not have
      diabetes, and the significant regional variations could represent inappropriate
      overuse or underuse. Although education and counselling for patients at risk for
      diabetes is clinically important, the volume of such persons served at Ontario
      diabetes education centres may detract from the centres' core function of
      supporting and managing patients already diagnosed with diabetes.

PMID- 24909090
TI  - Group medical visits in primary care for patients with diabetes and low
      socioeconomic status: users' perspectives and lessons for practitioners.
AB  - OBJECTIVE: This article describes a qualitative research study that examines the
      encounters by patients of low socioeconomic status with a group medical visit
      (GMV) program for individuals with or at risk for diabetes. The goal of this
      study was to generate insights that could be used to guide the development of an
      inner-city community health centre's GMV services. METHOD: Semistructured
      interviews were conducted with 9 patients who took part in a GMV program that was
      offered to patients of an inner-city community health centre that serves
      individuals with low income or homelessness. The interviews addressed barriers to
      and incentives for attending the GMV program, the GMV program's influence on
      diabetes-related knowledge and attitudes, and the patients' experience of health
      and quality of life. Conventional qualitative content analysis was used to
      organize the interview data according to themes and subthemes. RESULTS:
      Participants described how the GMV program was implemented, the qualities of a
      good facilitator, diabetes management as a change process, the role of group
      members in supporting the change process, and provided general feedback and
      suggestions. CONCLUSIONS: This article concludes with a series of considerations
      for the implementation of GMVs. These considerations address group cohesion, the
      therapeutic effects of group problem solving and support, and the implementation
      of behaviour-change interventions in GMVs.

PMID- 24909091
TI  - D-WISE: Diabetes Web-Centric Information and Support Environment: conceptual
      specification and proposed evaluation.
AB  - OBJECTIVE: To develop and evaluate Diabetes Web-Centric Information and Support
      Environment (D-WISE) that offers 1) a computerized decision-support system to
      assist physicians to A) use the Canadian Diabetes Association clinical practice
      guidelines (CDA CPGs) to recommend evidence-informed interventions; B) offer a
      computerized readiness assessment strategy to help physicians administer
      behaviour-change strategies to help patients adhere to disease self-management
      programs; and 2) a patient-specific diabetes self-management application,
      accessible through smart mobile devices, that offers behaviour-change
      interventions to engage patients in self-management. METHODS: The above-mentioned
      objectives were pursued through a knowledge management approach that involved 1)
      Translation of paper-based CDA CPGs and behaviour-change models as computerized
      decision-support tools that will assist physicians to offer evidence-informed and
      personalized diabetes management and behaviour-change strategies; 2) Engagement
      of patients in their diabetes care by generating a diabetes self-management
      program that takes into account their preferences, challenges and needs; 3)
      Empowering patients to self-manage their condition by providing them with
      personalized educational and motivational messages through a mobile self
      management application. The theoretical foundation of our research is grounded in
      behaviour-change models and healthcare knowledge management. We used 1) knowledge
      modelling to computerize the paper-based CDA CPGs and behaviour-change models, in
      particular, the behaviour-change strategy elements of A) readiness-to-change
      assessments; B) motivation-enhancement interventions categorized along the lines
      of patients' being ready, ambivalent or not ready; and C) self-efficacy
      enhancement. The CDA CPGs and the behaviour-change models are modelled and
      computerized in terms of A) a diabetes management ontology that serves as the
      knowledge resource for all the services offered by D-WISE; B) decision support
      services that use logic-based reasoning algorithms to utilize the knowledge
      encoded within the diabetes management ontology to assist physicians by
      recommending patient-specific diabetes-management interventions and behaviour
      change strategies; C) a mobile diabetes self-management application to engage and
      educate diabetes patients to self-manage their condition in a home-based setting
      while working in concert with their family physicians. RESULTS: We have been
      successful in creating and conducting a usability assessment of the physician
      decision support tool. These results will be published once the patient self-
      management application has been evaluated. CONCLUSIONS: D-WISE will be evaluated
      through pilot studies measuring 1) the usability of the e-Health interventions;
      and 2) the impact of the interventions on patients' behaviour changes and
      diabetes control.

PMID- 24909092
TI  - An innovative model of diabetes care and delivery: the St. Joseph's Primary Care
      Diabetes Support Program (SJHC PCDSP).
AB  - The majority of diabetes care in Canada is provided within the primary healthcare
      setting. It is delivered in a variety of models ranging from the physician
      working in a solo fee-for-service practice to an interprofessional team setting
      with specialist collaboration. To augment diabetes-related health services, the
      Ontario government has provided substantial funding to support community diabetes
      education programs. These models and initiatives are improving diabetes outcomes,
      and continued evolution of these programs can provide even greater outcomes. The
      St. Joseph's Primary Care Diabetes Support Program (SJHC PCDSP) is an innovative
      model that incorporates multidisciplinary allied health professionals together
      with physician support to provide care for more than 3000 patients in London,
      Ontario, Canada. It embodies the Canadian Diabetes Association (CDA)'s
      Organizations of Care recommendations to combine patient education and self
      management with active medical support at each clinic encounter, all while
      embodying the tenets of primary care. A brief review of primary healthcare reform
      is provided to explain how the SJHC PCDSP combines features of current models in
      a unique format so as to deliver exceptional patient care. By providing a
      detailed description of the services delivered at the SJHC PCDSP, it is hoped
      that both specialists and primary care providers consider using and adapting
      approaches to diabetes management based on this innovative model to optimize
      their practices. 

PMID- 24909093
TI  - Effect of exogenously administered glucagon versus spontaneous endogenous counter
      regulation on glycaemic recovery from insulin-induced hypoglycaemia in patients
      with type 2 diabetes treated with a novel glucokinase activator, AZD1656, and
      metformin.
AB  - AIMS: To study the effect of exogenous i.m. glucagon on recovery from controlled
      insulin-induced hypoglycaemia in patients with type 2 diabetes treated with the
      novel glucokinase activator AZD1656, in combination with metformin. METHODS: This
      was a single-centre randomized, open, two-way crossover phase I, automated
      glucose clamp (Biostator((r)); Life Science Instruments, Elkhart, MD, USA) study
      (NCT00817271) in eight patients (seven men and one woman, mean age 58.6 years,
      body mass index 28.1 kg/m(2)). All patients received a stable dose of metformin
      twice daily, ranging from 1000 to 2250 mg. A 2-day titration phase commenced with
      40 mg AZD1656 twice daily, escalating to 80 mg twice daily if tolerated. This was
      followed by a single dose of 80 or 160 mg AZD1656, administered on days 5 and 8
      when metabolic studies were performed. After an overnight fast on days 5 and 8,
      controlled hypoglycaemia was induced using an exogenous i.v. infusion of insulin.
      Plasma glucose was lowered in a stepwise fashion over 3 h to attain a target
      nadir of 2.7 mmol/l. This was sustained for 30 min, at the end of which the
      hypoglycaemic clamp was released. In random sequence, patients either received an
      i.m. injection of 1 mg glucagon or were allowed to recover from hypoglycaemia by
      endogenous counter-regulation. To avoid prolonged hypoglycaemia, a reverse
      glucose clamp was applied from 4 to 6 h post-dose. RESULTS: Three patients
      received 40 mg AZD1656 twice daily and five patients 80 mg twice daily. Mean
      plasma glucose at 20 min after release of the hypoglycaemic clamp was
      significantly lower (3.1 +/- 0.3 mmol/l) for AZD1656 alone than for AZD1656 +
      glucagon (4.9 +/- 0.8 mmol/l; p < 0.001 between the groups). Catecholamine and
      cortisol responses were similar on the AZD1656 + glucagon and AZD alone study
      days. Growth hormone response was 18% lower for AZD1656 alone (p = 0.01),
      consistent with the effect of a pharmacological dose of glucagon on growth
      hormone secretion. No safety or tolerability concerns were observed during
      treatment with AZ1656. CONCLUSIONS: Exogenous glucagon was effective as a rescue
      treatment for hypoglycaemia induced during treatment with AZD1656, given in
      combination with metformin in patients with type 2 diabetes.

PMID- 24909094
TI  - A nomogram predicting the risks of distant metastasis following postoperative
      radiotherapy for uterine cervical carcinoma: a Korean radiation oncology group
      study (KROG 12-08).
AB  - PURPOSE: To develop a nomogram predicting the risks of distant metastasis
      following postoperative adjuvant radiation therapy for early stage cervical
      cancer. MATERIALS AND METHODS: We reviewed the medical records of 1069 patients
      from ten participating institutions. Patients were divided into two cohorts: a
      training set (n=748) and a validation set (n=321). The demographic, clinical, and
      pathological variables were included in the univariate Cox proportional hazards
      analysis. Clinically established and statistically significant prognostic
      variables were utilized to develop a nomogram. RESULTS: The model was constructed
      using four variables: histologic type, pelvic lymph node involvement, depth of
      stromal invasion, and parametrial invasion. This model demonstrated good
      calibration and discrimination, with an internally validated concordance index of
      0.71 and an externally validated c-index of 0.65. Compared to FIGO staging, which
      showed a broad range in terms of distant metastasis, the developed nomogram can
      accurately predict individualized risks based on individual risk factors.
      CONCLUSIONS: The devised model offers a significantly accurate level of
      prediction and discrimination. In clinical practice it could be useful for
      counseling patients and selecting the patient group who could benefit from more
      intensive/further chemotherapy, once validated in a prospective patient cohort.

PMID- 24909095
TI  - Risk of second primary lung cancer in women after radiotherapy for breast cancer.
AB  - BACKGROUND: Several epidemiological studies have reported increased risks of
      second lung cancers after breast cancer irradiation. In this study we assessed
      the effects of the delivered radiation dose to the lung and the risk of second
      primary lung cancer. METHODS: We conducted a nested case-control study of second
      lung cancer in a population based cohort of 23,627 early breast cancer patients
      treated with post-operative radiotherapy from 1982 to 2007. The cohort included
      151 cases diagnosed with second primary lung cancer and 443 controls. Individual
      dose-reconstructions were performed and the delivered dose to the center of the
      second lung tumor and the comparable location for the controls were estimated,
      based on the patient specific radiotherapy charts. RESULTS: The median age at
      breast cancer diagnosis was 54 years (range 34-74). The median time from breast
      cancer treatment to second lung cancer diagnosis was 12 years (range 1-26 years).
      91% of the cases were categorized as ever smokers vs. 40% among the controls. For
      patients diagnosed with a second primary lung cancer five or more years after
      breast cancer treatment the rate of lung cancer increased linearly with 8.5% per
      Gray (95% confidence interval=3.1-23.3%; p<0.001). This rate was enhanced for
      ever smokers with an excess rate of 17.3% per Gray (95% CI=4.5-54%; p<0.005).
      CONCLUSIONS: Second lung cancer after radiotherapy for early breast cancer is
      associated with the delivered dose to the lung. Although the absolute risk is
      relative low, the growing number of long-time survivors after breast cancer
      treatment highlights the need for advances in normal tissue sparing radiation
      techniques.

PMID- 24909096
TI  - Inosine strongly enhances proliferation of human C32 melanoma cells through PLC
      PKC-MEK1/2-ERK1/2 and PI3K pathways.
AB  - Malignant melanoma is the most deadly type of skin cancer. The lack of effective
      pharmacological approaches for this tumour can be related to the incomplete
      understanding of the pathophysiological mechanisms involved in melanoma cell
      proliferation. Adenosine has growth-promoting and growth inhibitory effects on
      tumour cells. We aimed to investigate effects of adenosine and its metabolic
      product, inosine, on human C32 melanoma cells and the signalling pathways
      involved. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      reduction and bromodeoxyuridine (BrdU) proliferation assays were used to evaluate
      adenosine, adenosine deaminase and inosine effects, in the absence or presence of
      adenosine receptor (AR), A3 AR and P2Y1 R antagonists and PLC, PKC, MEK1/2 and
      PI3K inhibitors. ERK1/2 levels were determined using an ELISA kit. Adenosine and
      inosine levels were quantified using an enzyme-coupled assay. Adenosine caused
      cell proliferation through AR activation. Adenosine deaminase increased inosine
      levels (nanomolar concentrations) on the extracellular space, in a time-dependent
      manner, inducing proliferation through A3 AR activation. Micromolar
      concentrations of inosine enhanced proliferation through A3 AR activation,
      causing an increase in ERK1/2 levels, and P2Y1 R activation via ENT-dependent
      mechanisms. We propose the simultaneous activation of PLC-PKC-MEK1/2-ERK1/2 and
      PI3K pathways as the main mechanism responsible for the proliferative effect
      elicited by inosine and its significant role in melanoma cancer progression. 

PMID- 24909097
TI  - MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity
      in psoriasis.
AB  - BACKGROUND: Psoriasis is a systemic inflammatory skin disease. MicroRNAs (miRNAs)
      are a class of small non-coding RNA molecules that recently have been found in
      the blood to be relevant as disease biomarkers. OBJECTIVE: We aimed to explore
      miRNAs potential as blood biomarkers for psoriasis. METHODS: Using microarray and
      quantitative real-time PCR we measured the global miRNA expression in whole
      blood, plasma and peripheral blood mononuclear cells (PBMCs) from patients with
      psoriasis and healthy controls. RESULTS: We identified several deregulated miRNAs
      in the blood from patients with psoriasis including miR-223 and miR-143 which
      were found to be significantly upregulated in the PBMCs from patients with
      psoriasis compared with healthy controls (FCH=1.63, P<0.01; FCH=2.18, P<0.01,
      respectively). In addition, miR-223 and miR-143 significantly correlated with the
      PASIscore (r=0.46, P<0.05; r=0.55, P<0.02, respectively). Receiver-operating
      characteristic analysis (ROC) showed that miR-223 and -143 have the potential to
      distinguish between psoriasis and healthy controls (miR-223: area under the curve
      (AUC)=0.80, miR-143: AUC=0.75). Interestingly, after 3-5 weeks of treatment with
      methotrexate following a significant decrease in psoriasis severity, miR-223 and
      miR-143 were significantly downregulated in the PBMCs from patients with
      psoriasis. CONCLUSION: We suggest that changes in the miR-223 and miR-143
      expressions in PBMCs from patients with psoriasis may serve as novel biomarkers
      for disease activity in psoriasis; however, further investigations are warranted
      to clarify their specific roles.

PMID- 24909099
TI  - Linear immunoglobulin A disease and vancomycin: letter in reply.

PMID- 24909098
TI  - Performance of a novel wafer scale CMOS active pixel sensor for bio-medical
      imaging.
AB  - Recently CMOS active pixels sensors (APSs) have become a valuable alternative to
      amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging
      applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer
      size by means of a reticle stitching block process. However, despite wafer scale
      CMOS APS being monolithic, sources of non-uniformity of response and regional
      variations can persist representing a significant challenge for wafer scale
      sensor response. Non-uniformity of stitched sensors can arise from a number of
      factors related to the manufacturing process, including variation of
      amplification, variation between readout components, wafer defects and process
      variations across the wafer due to manufacturing processes. This paper reports on
      an investigation into the spatial non-uniformity and regional variations of a
      wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the
      electro-optical performance of a wafer CMOS APS is presented, to address
      inhomogeneity issues arising from the stitching techniques used to manufacture
      wafer scale sensors. A complete model of the signal generation in the pixel array
      has been provided and proved capable of accounting for noise and gain variations
      across the pixel array. This novel analysis leads to readout noise and conversion
      gain being evaluated at pixel level, stitching block level and in regions of
      interest, resulting in a coefficient of variation ?1.9%. The uniformity of the
      image quality performance has been further investigated in a typical x-ray
      application, i.e. mammography, showing a uniformity in terms of CNR among the
      highest when compared with mammography detectors commonly used in clinical
      practice. Finally, in order to compare the detection capability of this novel APS
      with the technology currently used (i.e. FPIs), theoretical evaluation of the
      detection quantum efficiency (DQE) at zero-frequency has been performed,
      resulting in a higher DQE for this detector compared to FPIs. Optical
      characterization, x-ray contrast measurements and theoretical DQE evaluation
      suggest that a trade off can be found between the need of a large imaging area
      and the requirement of a uniform imaging performance, making the DynAMITe large
      area CMOS APS suitable for a range of bio-medical applications. 

PMID- 24909100
TI  - Health risks of young adult travelers with type 1 diabetes.
AB  - AIM: International travel has become popular among young adults. This study
      evaluated the rate and characteristics of travel-associated health risks among
      young adults with type 1 diabetes mellitus (T1DM) compared with healthy same-aged
      individuals. METHODS: A retrospective study was conducted of 47 young adults with
      T1DM and 48 without (controls). Structured questionnaires accessed information
      regarding 154 international trips during the preceding 5 years and lasted 7 days
      and longer. RESULTS: Mean +/- SD ages of the diabetic and control groups were
      26.6 +/- 5.0 and 26.9 +/- 2.6 years, respectively. Mean trip durations were 80.0
      (range 7.0-390.0) and 87.6 days (range 7.0-395.0), respectively. The number of
      trips per person was 1.5 +/- 0.6 and 1.7 +/- 0.8, and the proportion of trips to
      developing countries 64 and 61%, respectively. There were no differences between
      the groups in rates of travel-related diseases that required medical consultation
      (11% vs 15% for all trips). No patient sought medical attention for acute
      problems related to diabetes management. Prior to 71% of their trips to
      developing countries, respondents with diabetes consulted their diabetes
      physician; prior to 26% of their trips they switched from an insulin pump to
      injections; during 41% of the trips they increased glucose monitoring; and for
      the period of 11% of the trips they defined their metabolic control as poor. Self
      reported mean hemoglobin A1c (HbA1c) levels before and after trips were 7.65 +/-
      1.45 and 7.81 +/- 1.23%, respectively (p = 0.42, paired t-test). CONCLUSIONS:
      Young adults with type 1 diabetes did not report more travel-related diseases
      than did healthy individuals. Most reported reasonable to good glycemic control
      during the trip without severe consequences.

PMID- 24909103
TI  - Efficacy of prevascularization for segmental bone defect repair using beta
      tricalcium phosphate scaffold in rhesus monkey.
AB  - Although small animal model (rabbit) showed successful bone defect repair using
      prevascularized tissue-engineered bone grafts (TEBG), large animal (rhesus
      monkey) studies are still needed to extrapolate the findings from animal data to
      humans. In current study, we investigated the efficacy of prevascularized TEBG
      for segmental bone defect repair in rhesus monkey. The segmental diaphyseal
      defects were created in both tibias. In group A, the defect was filled with
      prevascularized MSCs/scaffold prepared by inserting saphenous vascular bundle
      into the side groove and a fascia flap coverage; In group B, the defect was
      filled with MSCs/scaffold with a fascia flap coverage; In group C, the defect was
      filled with MSCs/scaffold; In group D, the defect was filled with only scaffold.
      The angiogenesis and new bone formation were compared among groups at 4, 8, and
      12 weeks postoperatively. The results showed the prevascularized TEBG in group A
      could augment new bone formation and capillary vessel in-growth. It had
      significantly higher values of vascularization and radiographic grading score
      compared with other groups. In conclusion, the in vivo experiment data of
      prevascularized TEBG was further enriched from small to large animal model. It
      implies that prevascularized TEBG has great potentials in clinical applications. 

PMID- 24909101
TI  - Barriers to implementing the "2008 Mexican Clinical Practice Guideline
      recommendations for the management of hip and knee osteoarthritis" in primary
      healthcare practice.
AB  - OBJECTIVE: To evaluate the implementability of the "2008 Mexican Clinical
      Practice Guideline for the management of hip and knee osteoarthritis at the
      primary level of care" within primary healthcare of three Mexican regions using
      the Guideline Implementability Appraisal methodology version 2 (GLIA.v2).
      METHODS: Six family physicians, representing the South, North, and Central
      Mexico, and one Mexican physiatrist evaluated the 45 recommendations stated by
      the Mexican guideline. The GLIA.v2 methodology includes the execution of
      qualitative and semi-quantitative techniques. RESULTS: Reviewers' agreement was
      between moderate to near complete in most cases. Sixty-nine percent of the
      recommendations were considered difficult to implement within clinical practice.
      Eight recommendations did not have an appropriate format. Only 6 recommendations
      were judged as able to be consistently applied to clinical practice. Barriers
      related to the context of one or more institutions/regions were identified in 25
      recommendations. These barriers are related to health providers/patients'
      beliefs, processes of care within each institution, and availability of some
      treatments recommended by the guideline. CONCLUSIONS: The guideline presented
      problems of conciseness and clarity that negatively affect its application within
      the Mexican primary healthcare context. We identified individual, organizational
      and system characteristics, which are common to the 3 institutions/regions
      studied and constitute barriers for implementing the guideline to clinical
      practice. It is recommended that the 2008-Mexican-CPG-OA be thoroughly revised
      and restructured to improve the clarity of the actions implied by each
      recommendation. We propose some strategies to accomplish this and to overcome
      some of the identified regional/institutional barriers.

PMID- 24909102
TI  - Substrate-dependent modulation of 3D spheroid morphology self-assembled in
      mesenchymal stem cell-endothelial progenitor cell coculture.
AB  - The structural evolution of three-dimensional spheroids self-assembled from two
      different types of cells on selective biomaterials is demonstrated in this study.
      The two types of cells involved in the self-assembly are human mesenchymal stem
      cells (MSCs) and endothelial progenitor cells (EPCs). When seeded in different
      population ratios, they can create a variety of cellular patterns on different
      biomaterial substrates. When the two populations are matched in initial numbers,
      they are self-assembled in co-spheroids with different morphologies (i.e.
      randomly mixed, bumped, or concentric spheroids). The morphologies are influenced
      by the specific cell-substrate interaction possibly through integrin signaling,
      as well as a substrate-dependent regulation of heterophilic cell-cell interaction
      possibly through Notch signaling. In particular, the self-assembled core-shell
      concentric spheroids from adipose-derived MSCs and EPCs show a greater angiogenic
      effect in vitro. This study reveals the possibility to modulate the self
      assembled morphology as well as the effect of cocultured cells by changing the
      cell culture substratum. 

PMID- 24909104
TI  - Leishmania donovani eukaryotic initiation factor 5A: molecular characterization,
      localization and homology modelling studies.
AB  - Eukaryotic translation initiation factor 5A (eIF5A) is a small acidic protein
      highly conserved from archaea to mammals. eIF5A is the only protein which
      undergoes a unique lysine residue modification to hypusine. Hypusinylation is
      important for the function of eIF5A which is reported to be essential for cell
      viability. eIF5A promotes formation of the first peptide bond at the onset of
      protein synthesis. However, its function in Leishmania donovani is unclear. The
      present study focuses on the characterization and localization of L. donovani
      eIF5A protein. The eIF5A gene contains an ORF of 501*bp encoding 166 amino acid
      residues with a predicted molecular mass and isoelectric point of 17.8 kDa and
      4.83 respectively. A phylogenetic tree analysis revealed its close proximity to
      trypanosomes however it is distantly located from Trichomonas vaginalis and
      Plasmodium falciparum. The L. donovani eIF5A was expressed as a 6* His tagged
      protein whose identity was confirmed by western blot and MALDI. Biophysical
      investigation by CD revealed the predominant presence of 49% beta sheet structure
      which correlated well with secondary structure prediction. To gain insight into
      the role of eIF5A in L. donovani, we investigated the subcellular distribution of
      eIF5A. A GFP-fusion of L. donovani eIF5A was found to be localized in cytoplasm
      as confirmed by subcellular fractionation. Our studies indicated that eIF5A is
      primarily localized to cytoplasm and is undetectable in nuclear fraction. The
      homology model of eIF5A of L. donovani was built and the resulting model showed
      acceptable Ramachandran statistics. The model is reliable and can be used to
      study eIF5A binding with its effector molecules.

PMID- 24909105
TI  - Postural and dynamic balance while walking in adults with incomplete spinal cord
      injury.
AB  - The purpose of this study was to characterize balance in individuals with and
      without an incomplete spinal cord injury (ISCI) during the single support phase
      of gait. Thirty-four individuals (17 with a ISCI, 17 able-bodied) walked at their
      self-selected walking speed. Among those, eighteen individuals (9 with ISCI, 9
      able-bodied) with a similar walking speed were also analyzed. Stabilizing and
      destabilizing forces quantified balance during the single support phase of gait.
      The biomechanical factors included in the equation of the stabilizing and
      destabilizing forces served as explanatory factors. Individuals with ISCI had a
      lower stabilizing force and a higher destabilizing force compared to able-bodied
      individuals. The main explanatory factors of the forces extracted from the
      equations were the speed of the center of mass (maximal stabilizing force) and
      the distance between the center of pressure and the base of support (minimal
      destabilizing force). Only the minimal destabilizing force was significantly
      different among subgroups with a similar walking speed. The stabilizing and
      destabilizing forces suggest that individuals with ISCI were more stable than
      able-bodied, which was achieved by walking more slowly - which decrease the speed
      of the center of mass - and keeping the center of pressure away from the margin
      of the base of support in order to maintain balance within their range of
      physical ability. 

PMID- 24909106
TI  - Management of pediatric status epilepticus.
AB  - OPINION STATEMENT: Status epilepticus (SE) is a medical emergency consisting of
      persistent or recurring seizures without a return to baseline mental status. SE
      can be divided into subtypes based on seizure types and underlying etiologies.
      Management should be implemented rapidly and based on pre-determined care
      pathways. The aim is to terminate seizures while simultaneously identifying and
      managing precipitant conditions. Seizure management involves "emergent" treatment
      with benzodiazepines (lorazepam intravenously, midazolam intramuscularly, or
      diazepam rectally) followed by "urgent" therapy (phenytoin/fosphenytoin,
      phenobarbital, levetiracetam or valproate sodium). If seizures persist,
      "refractory" treatments include infusions of midazolam or pentobarbital.
      Prognosis is dependent on the underlying etiology and seizure persistence. This
      article reviews the current management strategies for pediatric convulsive SE.

PMID- 24909107
TI  - Outcomes of surgical revascularization for lower extremity arterial
      thromboembolism in patients with advanced malignancy.
AB  - OBJECTIVE: The objective of this study was to describe the outcomes of surgical
      revascularization for lower extremity arterial thromboembolism in patients with
      advanced malignancy. METHODS: The 2005-2011 American College of Surgeons National
      Surgical Quality Improvement Program database was used for this study.
      Preoperative characteristics and postoperative outcomes of patients with known
      advanced malignancy who underwent surgical revascularization for lower extremity
      arterial thromboembolic disease were assessed and compared with those of patients
      without known advanced malignancy. Parsimonious multivariate logistic regression
      analysis was used to determine the independent association between advanced
      malignancy and 30-day postoperative mortality and morbidity after adjustment for
      demographic characteristics, acute and chronic comorbid disease burden, history
      of peripheral arterial disease, functional and nutritional status, acuity of
      presentation, and procedure type. RESULTS: The study included 136 patients with
      advanced malignancy who underwent surgical revascularization for lower extremity
      arterial thromboembolism for analysis (65% thromboembolectomy, 26%
      thromboendarterectomy, and 22% bypass grafting). The 30-day mortality and
      morbidity rates in these patients were 30.2% and 38.2%, respectively. Compared
      with patients without advanced malignancy, patients with advanced malignancy had
      a significantly greater risk of postoperative death (adjusted odds ratio, 5.92;
      95% confidence interval, 3.69-9.52; P < .001) but not morbidity (adjusted odds
      ratio, 1.28; 95% confidence interval, 0.87-1.87; P = .21). CONCLUSIONS: Our study
      is the largest to date to describe the outcomes of patients with advanced
      malignancy who undergo surgical revascularization for arterial thromboembolism of
      the lower extremities. Such patients suffer high rates of early postoperative
      mortality and morbidity, especially when emergency operation is required. Early
      involvement of palliative care specialists is warranted in these patients to
      ensure that the decision to pursue surgical revascularization is aligned with
      their goals of care.

PMID- 24909108
TI  - Split reality for novel tick virus.

PMID- 24909110
TI  - Bacterial secretion: A trans-kingdom effector.

PMID- 24909111
TI  - K-Cl cotransporter KCC2--a moonlighting protein in excitatory and inhibitory
      synapse development and function.
AB  - The K-Cl cotransporter KCC2 has two entirely independent biological actions as
      either an ion transporter or a structural protein orchestrating the organization
      of the cytoskeleton in neuronal structures. The K-Cl cotransport by KCC2 is
      central for hyperpolarizing inhibitory signaling, which is based on chloride
      currents mediated by gamma-aminobutyric acid (GABA)- or glycine-gated receptor
      channels. In contrast, the structural role of KCC2 seems to be crucially involved
      in the maturation and regulation of excitatory glutamatergic synapses. This dual
      role at GABAergic/glycinergic and glutamatergic synapses makes KCC2 a key
      molecule in the regulation of inhibitory and excitatory signaling. Therefore,
      KCC2 is most likely involved in the synchronization of the two types of activity
      during network formation in the immature system and a similar synchronizing role
      might also be important under physiological and pathological conditions in mature
      neuronal networks. In this review, we explore new findings on the regulation of
      KCC2 by protease-mediated cleavage and on the structural role of KCC2 in spine
      morphogenesis and glutamate receptor clustering. We then discuss the implications
      of the putative interaction between the independent functions of the transporter
      and overlapping regulatory mechanisms in a neurophysiological context. In
      addition, we look at the multifunctional properties of KCC2 in the light of
      evolution and propose that KCC2 belongs to the group of moonlighting
      (multifunctional) proteins. 

PMID- 24909112
TI  - Effects of marital status and shift work on family function among registered
      nurses.
AB  - This study aims to assess the interactive effect of marital status and shift work
      on family function. A population-based sample of 1,438 nurses between the ages of
      20-45 yr was recruited from Taiwan during the period from July 2005 to April 2006
      using a mailed questionnaire. The self-administered questionnaire contained
      information about demographic data, work status, shift work schedule, and the
      Family APGAR (Adaptation, Partnership, Growth, Affection, and Resolve) Scale, to
      evaluate family function. Compared to day shift nurses, non-night and rotation
      shift nurses had 1.53- and 1.38-fold (95% CI=1.09-2.14 and 1.01-1.88) risk to
      have poor family function after adjusting for other covariates. Married nurses,
      by contrast, had a 0.44-fold (95% CI=0.29-0.66) risk to have poor family function
      compared to single nurses. In addition, married nurses who worked non-night or
      rotation shifts had a significantly higher percent of poor family function than
      those married nurses working day shifts; however, similar results were not
      replicated in single nurses. We concluded that shift work and marital status
      could influence family function. 

PMID- 24909109
TI  - Unravelling the structural and mechanistic basis of CRISPR-Cas systems.
AB  - Bacteria and archaea have evolved sophisticated adaptive immune systems, known as
      CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR
      associated proteins) systems, which target and inactivate invading viruses and
      plasmids. Immunity is acquired by integrating short fragments of foreign DNA into
      CRISPR loci, and following transcription and processing of these loci, the CRISPR
      RNAs (crRNAs) guide the Cas proteins to complementary invading nucleic acid,
      which results in target interference. In this Review, we summarize the recent
      structural and biochemical insights that have been gained for the three major
      types of CRISPR-Cas systems, which together provide a detailed molecular
      understanding of the unique and conserved mechanisms of RNA-guided adaptive
      immunity in bacteria and archaea. 

PMID- 24909113
TI  - Height, its components, and coagulability among older Chinese: the Guangzhou
      biobank cohort study.
AB  - OBJECTIVES: The causal role of some cardiovascular risk factors, such as HDL
      cholesterol, has been increasingly challenged and attention is returning to all
      elements of Virchow's triad, i.e., hypercoagulability (including viscosity) as
      well as endothelial function and blood flow. We examined the life course origins
      of coagulability. METHODS: We used multivariable linear regression to assess
      whether childhood influences, proxied by height and its components, were
      associated with hematocrit (Hct), hemoglobin (HGB), and other hematological
      parameters in 28,595 older Chinese adults (mean age = 61.8 years) from the
      Guangzhou Biobank Cohort Study. RESULTS: Adjusted for age, sex, and recruitment
      phase, leg length was negatively associated with platelets (PLT) (-0.83 * 10(9)
      /l per centimeter (cm), 95% confidence interval (CI) -1.01 to -0.65). Sitting
      height and height were positively associated with Hct (0.05% per cm, 95% CI 0.04
      0.07 for sitting height; 0.02% per cm, 95% CI 0.01-0.02 for height), HGB (0.21
      g/l per cm, 95% CI 0.17-0.25; 0.07 g/l per cm, 95% CI 0.04-0.09) and negatively
      associated with PLT (-1.2 * 10(9) /l per cm, 95% CI -1.4 to -1.0; -0.83 * 10(9)
      /l per cm, 95% CI -0.95 to -0.70). Further adjustment for potential confounders
      did little to change the estimates. CONCLUSIONS: For the first time we provide
      anthropometric evidence for the different roles of prepubertal and pubertal
      influences in relation to Hct and HGB. Whether factors that promote leg growth
      but reduce growth of sitting height may help to prevent cardiovascular events,
      via effects on hypercoagulability or viscosity, overall or in specific subgroups,
      remains to be determined.

PMID- 24909114
TI  - Human chimera-type galectin-3: defining the critical tail length for high
      affinity glycoprotein/cell surface binding and functional competition with
      galectin-1 in neuroblastoma cell growth regulation.
AB  - Many human proteins have a modular design with receptor and structural domains.
      Using adhesion/growth-regulatory galectin-3 as model, we describe an
      interdisciplinary strategy to define the functional significance of its tail
      established by nine non-triple helical collagen-like repeats (I-IX) and the N
      terminal peptide. Genetic engineering with sophisticated mass spectrometric
      product analysis provided the tools for biotesting, i.e. eight protein variants
      with different degrees of tail truncation. Evidently,various aspects of galectin
      3 activity (cis binding and cell bridging) are affected by tail shortening in a
      different manner. Thus, this combined approach reveals an unsuspected complexity
      of structure-function relationship, encouraging further application beyond this
      chimera-type galectin. 

PMID- 24909116
TI  - Cerebral ischaemia after repair of coarctation of the aorta.
AB  - A 9-year-old boy, with a history of repair of severe coarctation of the aorta
      through balloon angioplasty 2 weeks ago, presented in the emergency paediatric
      department with symptoms consistent with transient cerebral ischaemia. MRI
      revealed an area of cerebral infarction in the right frontal lobe. Causes of
      cerebral ischaemia after aortic coarctation repair are briefly discussed. 

PMID- 24909115
TI  - Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma:
      plausible role in tumorigenesis.
AB  - Renal cell carcinoma (RCC) is the most common kidney cancer in adults. Although
      several genes have been found to be involved in carcinogenesis of RCC, more great
      efforts are needed to identify new genes which are responsible for the process.
      Clear cell RCC, originates from proximal tubule cells, is the most common
      pathological type of RCC. Alkaline phosphatase (ALP) is a marker enzyme of brush
      border membrane of proximal tubular cells. Our previous studies showed a
      significant decreased activity of Liver/Bone/Kidney (L/B/K) alkaline phosphatase
      in RCC. In the present study, we explored the molecular basis of the decreased
      activity of ALP in RCC. Immunohistochemistry, immunofluorescence and flow
      cytometry analysis showed decreased ALP protein in RCC. Additionally, real time
      PCR documented significantly reduced ALP gene expression (P = 0.009). Moreover,
      RCC cell lines (ACHN and A498) transfected with full length L/B/K cDNA showed
      decreased migratory property as well as viability of these cells as compared with
      controls (P = 0.000). Further, L/B/K ALP cDNA transfected cells (ACHN and A498)
      showed significant increased apoptosis as compared to control (P = 0.000). These
      findings suggest the new role of ALP in cell viability and apoptosis and
      involvement in RCC tumorigenesis. However, further studies are needed to explore
      the exact molecular mechanism. 

PMID- 24909117
TI  - Monozygotic twins with 17q21.31 microdeletion syndrome.
AB  - Chromosome 17q21.31 microdeletion syndrome is a genomic disorder caused by a
      recurrent 600 kb long deletion. The deletion affects the region of a common
      inversion present in about 20% of Europeans. The inversion is associated with the
      H2 haplotype carrying additional low-copy repeats susceptible to non-allelic
      homologous recombination, and this haplotype is prone to deletion. No instances
      of 17q21.31 deletions inherited from an affected parent have been reported, and
      the deletions always affected a parental chromosome with the H2 haplotype. The
      syndrome is characterized clinically by intellectual disability, hypotonia,
      friendly behavior and specific facial dysmorphism with long face, large tubular
      or pear-shaped nose and bulbous nasal tip. We present monozygotic twin sisters
      showing the typical clinical picture of the syndrome. The phenotype of the
      sisters was very similar, with a slightly more severe presentation in Twin B. The
      17q21.31 microdeletion was confirmed in both patients but in neither of their
      parents. Potential copy number differences between the genomes of the twins were
      subsequently searched using high-resolution single nucleotide polymorphism (SNP)
      and comparative genome hybridisation (CGH) arrays. However, these analyses
      identified no additional aberrations or genomic differences that could
      potentially be responsible for the subtle phenotypic differences. These could
      possibly be related to the more severe perinatal history of Twin B, or to the
      variable expressivity of the disorder. In accord with the expectations, one of
      the parents (the mother) was shown to carry the H2 haplotype, and the maternal
      allele of chromosome 17q21.31 was missing in the twins. 

PMID- 24909118
TI  - Emodin inhibits tonic tension through suppressing PKCdelta-mediated inhibition of
      myosin phosphatase in rat isolated thoracic aorta.
AB  - BACKGROUND AND PURPOSE: Dysregulated tonic tension and calcium sensitization in
      blood vessels has frequently been observed in many cardiovascular diseases.
      Despite a huge therapeutic potential, little is known about natural products
      targeting tonic tension and calcium sensitization. EXPERIMENTAL APPROACH: We
      screened natural products for inhibitory effects on vasoconstriction using the
      rat isolated thoracic aorta and found that an anthraquinone derivative, emodin,
      attenuated tonic tension. Organ bath system, primary vascular smooth muscle
      cells, confocal microscopy and Western blot analysis were employed to demonstrate
      the suppressive effects of emodin on PKCdelta-mediated myosin phosphatase
      inhibition. KEY RESULTS: Emodin, an active ingredient of Polygonum multiflorum
      extract, inhibited phenylephrine-induced vasoconstriction in rat isolated
      thoracic aorta, and inhibited vasoconstriction induced by 5-HT and endothelin-1.
      It also generally suppressed vasoconstrictions mediated by voltage-operated,
      store-operated calcium channels and intracellular calcium store. However, emodin
      did not affect agonist-induced calcium increases in primary smooth muscle cells.
      In contrast, post-treatment with emodin following phenylephrine stimulation
      potently suppressed tonic tension in rat aortic rings. Western blot analysis
      revealed that emodin inhibited phenylephrine-induced phospho-myosin light chain
      (pMLC) and the phosphorylation of myosin-targeting subunit and C-kinase-activated
      protein phosphatase-1 inhibitor (CPI-17). This was mediated by selective
      inhibition of PKCdelta, whereas PKCalpha was not involved. CONCLUSION AND
      IMPLICATIONS: Emodin attenuates tonic tension through the blockade of PKCdelta
      and CPI-17-mediated MLC-phosphatase inhibition. This new mode of action for the
      suppression of tonic tension and structural insights into PKCdelta inhibition
      revealed by emodin may provide new information for the development of modulators
      of tonic tension and for the treatment of hypertension.

PMID- 24909119
TI  - Acute exposure to a common suspended sediment affects the swimming performance
      and physiology of juvenile salmonids.
AB  - To study the effects of an acute exposure to turbidity generated by suspended
      sediment, we examined swimming performance (Ucrit) and related metabolic
      parameters in individual and groups of juvenile trout at three different
      concentrations of calcium carbonate. To investigate differences among strains or
      provenience, we compared one strain of rainbow trout (Oncorhynchus mykiss; RBT)
      and one strain of brown trout (Salmo trutta; BNT) from a common hatchery and one
      RBT strain from a separate hatchery. In general, trout swum individually or in
      groups exhibited a decrease in Ucrit as turbidity increased. Both RBT strains
      were more similar to each other and were impaired to a larger extent in swimming
      performance than BNT, which was less impacted. For groups, indicators of aerobic
      metabolism were elevated while those of anaerobic metabolism were depressed.
      Specifically, citrate synthase activities and glucose levels tended to be greater
      while plasma lactate and LDH activities were reduced. Lactate and LDH levels in
      individually swum trout under sediment exposure suggest a greater similarity of
      fish from the same provenience. We suggest that acute exposures to
      environmentally relevant turbidities generated by fine suspended sediment may
      cause a reduced Ucrit, and that these changes may be related to changes in the
      utilization of aerobic and anaerobic pathways. 

PMID- 24909120
TI  - Heat-induced post-stress growth delay: a biological trait of many Metarhizium
      isolates reducing biocontrol efficacy?
AB  - The habitats of many pest insects have fluctuating climatic conditions. To
      function effectively, the pathogens of these pests must be capable of infecting
      and developing disease at a wide range of temperatures. The current study
      examines ten Metarhizium spp. isolates as to their ability to recover normal
      metabolic activity after exposure to high temperature for several hours daily;
      and whether such recovery, with at least some isolates, requires a temporary
      repair ("retooling") period. Fungal colonies were exposed to 40 degrees C for 4h
      or 8h followed by 20h or 16h at 28 degrees C, respectively, for three consecutive
      days. Growth rates during treatments were compared to control plates (constant 28
      degrees C) and to plates with growth stoppage by cold treatment (4h or 8h at 5
      degrees C per day). All ten isolates survived 3days of cycled heat treatment and
      resumed normal growth afterward; some isolates however, were considerably more
      negatively affected by heat-cycling than others. In fact, some isolates underwent
      greatly reduced growth not only during 8h heating, but also some hours after
      cessation of heat treatment. This phenomenon is labeled in the current study as
      "post-stress growth delay" (PSGD). In contrast, all isolates stopped growing
      during 8h cold treatments, but immediately recommenced growing on return to 28
      degrees C. The delay in recommencing growth of some isolates after heat treatment
      amplifies the effect of this stress. In addition to the studies on the effects of
      heat cycling on fungal cultures, the effects of imposing such temperature cycling
      on fungal infection of insects was documented in the laboratory. Three
      Metarhizium isolates were bioassayed using Galleria mellonella larvae. Treated
      insects were placed at daily temperature regimes matching those used for the in
      vitro fungus rate-of-growth study, and insect mortality recorded daily. For all
      three isolates the levels of insect mortality at the highest-heat dose (40
      degrees C at 8h daily) significantly reduced infection. Fluctuating temperatures
      are likely to be a factor in most pest-insect habitats; therefore, the presence
      and level of PSGD of each isolate should be a primary consideration in selecting
      field-appropriate fungal isolates. 

PMID- 24909121
TI  - A piglet model for studying Candida albicans colonization of the human oro
      gastrointestinal tract.
AB  - Pigs from a variety of sources were surveyed for oro-gastrointestinal (oro-GIT)
      carriage of Candida albicans. Candida albicans-positive animals were readily
      located, but we also identified C. albicans-free pigs. We hypothesized that pigs
      could be stably colonized with a C. albicans strain of choice, simply by feeding
      yeast cells. Piglets were farrowed routinely and remained with the sow for 4 days
      to acquire a normal microbiota. Piglets were then placed in an artificial rearing
      environment and fed sow milk replacer. Piglets were inoculated orally with one of
      three different C. albicans strains. Piglets were weighed daily, and culture
      swabs were collected to detect C. albicans orally, rectally and in the piglet's
      environment. Stable C. albicans colonization over the course of the study did not
      affect piglet growth. Necropsy revealed mucosally associated C. albicans
      throughout the oro-GIT with the highest abundance in the esophagus. Uninoculated
      control piglets remained C. albicans-negative. These data establish the piglet as
      a model to study C. albicans colonization of the human oro-GIT. Similarities
      between oro-GIT colonization in humans and pigs, as well as the ease of working
      with the piglet model, suggest its adaptability for use among investigators
      interested in understanding C. albicans-host commensal interactions.

PMID- 24909123
TI  - A nanoscale bio-inspired light-harvesting system developed from self-assembled
      alkyl-functionalized metallochlorin nano-aggregates.
AB  - Self-assembled supramolecular organization of nano-structured biomimetic light
      harvesting modules inside solid-state nano-templates can be exploited to develop
      excellent light-harvesting materials for artificial photosynthetic devices. We
      present here a hybrid light-harvesting system mimicking the chlorosomal
      structures of the natural photosynthetic system using synthetic zinc chlorin
      units (ZnChl-C6, ZnChl-C12 and ZnChl-C18) that are self-aggregated inside the
      anodic aluminum oxide (AAO) nano-channel membranes. AAO nano-templates were
      modified with a TiO2 matrix and functionalized with long hydrophobic chains to
      facilitate the formation of supramolecular Zn-chlorin aggregates. The transparent
      Zn-chlorin nano-aggregates inside the alkyl-TiO2 modified AAO nano-channels have
      a diameter of ~120 nm in a 60 MUm length channel. UV-Vis studies and fluorescence
      emission spectra further confirm the formation of the supramolecular ZnChl
      aggregates from monomer molecules inside the alkyl-functionalized nano-channels.
      Our results prove that the novel and unique method can be used to produce
      efficient and stable light-harvesting assemblies for effective solar energy
      capture through transparent and stable nano-channel ceramic materials modified
      with bio-mimetic molecular self-assembled nano-aggregates. 

PMID- 24909122
TI  - Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced
      inflammatory response in human monocytes.
AB  - Early reports indicate that long non-coding RNAs (lncRNAs) are novel regulators
      of biological responses. However, their role in the human innate immune response,
      which provides the initial defence against infection, is largely unexplored. To
      address this issue, here we characterize the long non-coding RNA transcriptome in
      primary human monocytes using RNA sequencing. We identify 76 enhancer RNAs
      (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of
      bidirectional transcription (RBT) that are differentially expressed in response
      to bacterial lipopolysaccharide (LPS). Crucially, we demonstrate that knockdown
      of nuclear-localized, NF-kappaB-regulated, eRNAs (IL1beta-eRNA) and RBT (IL1beta
      RBT46) surrounding the IL1beta locus, attenuates LPS-induced messenger RNA
      transcription and release of the proinflammatory mediators, IL1beta and CXCL8. We
      predict that lncRNAs can be important regulators of the human innate immune
      response. 

PMID- 24909124
TI  - Clinical and radiological findings in methadone-induced delayed
      leukoencephalopathy.
AB  - OBJECTIVE: To increase awareness of the incidence of delayed leukoencephalopathy
      in rehabilitation medicine. SUBJECT: A 34-year-old male patient in an inpatient
      neuro-rehabilitation clinic who developed cognitive, psychological and physical
      deterioration 33 days after methadone intake. METHODS: Clinical follow-up for 7
      months, brain imaging with magnetic resonance imaging and computed tomography,
      electroencephalography, multidisciplinary team evaluation and rehabilitation,
      pharmacological treatment, and examination of medical records. RESULTS: Clinical
      findings showed neuropsychological and motor deterioration. Brain images
      demonstrated that previous white matter infarctions had developed to cystic
      substance defects, and that abnormally high signals developed in the white matter
      of most cerebral lobes, with the exception of the grey matter and the cerebellum.
      Clinical improvement coincided with a modification in pharmacological treatment
      (increase in sertraline and introduction of baclofen). Brain images at 3 and 6
      months after the methadone overdose showed reduced intensity of signal
      abnormalities and complete normalization of diffusion weighted images. Evaluation
      7 months after injury estimated moderate brain injury with moderate disability
      and partial recovery of the patient's capacity for previous activities of daily
      living. CONCLUSION: Delayed leukoencephalopathy should be suspected in patients
      who deteriorate after methadone overdose. Drugs such as sertraline and baclofen
      may be of use in treating delayed leukoencephalopathy.

PMID- 24909125
TI  - Editorial overview: Musculoskeletal: Are we on the road to personalised medicine
      in musculoskeletal diseases?

PMID- 24909126
TI  - Immunoglobulin M oligoclonal bands: biomarker of targetable inflammation in
      primary progressive multiple sclerosis.
AB  - OBJECTIVE: To identify a biomarker distinguishing patients who, despite a primary
      progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit
      from immune therapy. METHODS: The presence or absence of both immunoglobulin (Ig)
      G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal
      fluid (CSF) and serum samples from a large PPMS patient cohort, and related to
      clinical and imaging evidence of focal inflammatory disease activity. RESULTS:
      Using both cross-sectional samples and serial sampling in a subgroup of patients
      followed prospectively as part of the placebo-controlled OLYMPUS study of
      rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not
      of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS
      patients. This finding was confirmed in an independent, multicenter validation
      cohort. INTERPRETATION: The presence of CSF IgM OCB may be a biomarker for a
      subset of PPMS patients with more active inflammatory disease, who may benefit
      from immune-directed treatments.

PMID- 24909127
TI  - Morphogenesis of the tongue mucosa in the domestic duck (Anas platyrhynchos f.
      domestica) during the late embryonic stages.
AB  - The tongue in domestic duck, as in other Anseriformes, is characterized by wide
      variety of shape and mechanical papillae and they fulfill different function
      during food collection. The present work aims to describe morphological features
      of the tongue as well as the pace formation of the mechanical papillae during
      embryonic period. The results may allow to answer whether the tongue in duck is
      ready to fulfill feeding function after hatching. The study revealed that the
      particular part of the tongue and the conical papillae of the body develop
      between 10th and 16th day of incubation, from the caudal part of the body into
      the rostral part of the tongue. The conical papillae of the lingual prominence in
      the first row are formed from 11th to 16th day and in the second row at the turn
      of the 15th and 16th day of incubation. These papillae developed symmetrically
      from the median part of the lingual prominence, to its edges. The lingual comb,
      which is used during transport of the food particles, is formed between 16th and
      19th day. The present study indicated the morphological changes of the particular
      part of the tongue and the mechanical papillae were varied between the
      developmental stages. The morphology of the tongue in the domestic duck is fully
      developed before hatching and ready to collect food by pecking and grazing.
      However, filter-feeding mechanism is not still obvious.

PMID- 24909128
TI  - Importance of guiding catheter disengagement during measurement of fractional
      flow reserve in patients with an isolated proximal left anterior descending
      artery stenosis.
AB  - OBJECTIVE: To determine the impact of ostial guiding catheter disengagement
      during measurement of fractional flow reserve (FFR) in patients with an isolated
      proximal left anterior descending artery (LAD) stenosis. METHODS: Measurements of
      FFR were performed in 21 patients with an isolated intermediate lesion of the
      proximal LAD. Proximal aortic pressure (Pa), distal post stenotic pressure (Pd),
      and Pd/Pa were recorded at baseline, after at least 90 sec of intravenous (IV)
      adenosine infusion with the guiding catheter still engaged in the coronary ostium
      (Pa1 , Pd1 , FFReng ), and after at least 30 sec of guiding catheter
      disengagement back to the aorta (Pa2 , Pd2 , FFRdis ). RESULTS: The average value
      of Pd/Pa at baseline was 0.92 +/- 0.04. After 110 +/- 8 sec of IV adenosine
      infusion, FFReng was 0.81 +/- 0.07, which decreased to 0.77 +/- 0.08 (FFRdis )
      after 38 +/- 6 sec of guiding catheter disengagement. The mean DeltaFFR (FFReng  
      FFRdis ) was 0.05 +/- 0.04. As compared to baseline values, the mean change in
      FFR values was significantly increased after disengagement of the guiding
      catheter (Pd/Pabaseline  - FFRdis vs. Pd/Pabaseline  - FFReng , 0.15 +/- 0.05 vs.
      0.10 +/- 0.04, P < 0.0001). Before guiding catheter disengagement, eight patients
      (38%) had an FFR value <= 0.8. Following disengagement of the guiding catheter,
      the new FFR values decreased below 0.8 in six additional patients (28%), with
      subsequent change in treatment strategy. CONCLUSIONS: During FFR assessment of
      isolated intermediate proximal LAD lesions, guiding catheter disengagement is
      associated with a decrease in mean FFR values. In patients with FFR values lying
      close to the treatment threshold, this can have an impact on treatment strategy.

PMID- 24909129
TI  - Methotrexate and lung disease in rheumatoid arthritis: comment on the article by
      Conway et al.

PMID- 24909130
TI  - Move more, eat less: it's time for Americans to get serious about exercise.

PMID- 24909132
TI  - Comparative profiling of the sperm proteome.
AB  - The highly complex and species-selective mechanism of fertilization is a central
      theme of developmental biology. Gametogenesis, sperm activation, and egg-sperm
      recognition are fundamental biological processes, warranting detailed studies
      into the molecular composition of gametes. Biological MS has been instrumental
      for the comprehensive itemizing of gamete proteomes. The protein constellation of
      sperm cells and its subcellular structures has been established for a variety of
      animal species. Spermatogenesis and the crucial activation of sperm cells as a
      prerequisite of successful fertilization and physiological adaptations to
      external stressors was investigated using proteomics, as well as the underlying
      mechanisms of male infertility with respect to proteome-wide alterations. This
      review outlines recent achievements of sperm proteomics and exemplifies the
      usefulness of gel-based surveys by outlining the comparative analysis of abnormal
      spermatozoa in globozoospermia. Besides label-free MS techniques and cell-based
      labeling methodology, high-resolution fluorescence 2DE has been shown to be
      highly suitable as a proteomic biomarker discovery tool in sperm protein
      research. The appropriateness of novel protein markers for improving our
      understanding of normal spermatogenesis and sperm activation versus the molecular
      pathogenesis of male infertility will be discussed. New biomarker candidates
      might be useful to improve diagnostic, prognostic, and therapeutic aspects of
      infertility. 

PMID- 24909133
TI  - Heteroatom-doped highly porous carbon from human urine.
AB  - Human urine, otherwise potentially polluting waste, is an universal unused
      resource in organic form disposed by the human body. We present for the first
      time "proof of concept" of a convenient, perhaps economically beneficial, and
      innovative template-free route to synthesize highly porous carbon containing
      heteroatoms such as N, S, Si, and P from human urine waste as a single precursor
      for carbon and multiple heteroatoms. High porosity is created through removal of
      inherently-present salt particles in as-prepared "Urine Carbon" (URC), and
      multiple heteroatoms are naturally doped into the carbon, making it unnecessary
      to employ troublesome expensive pore-generating templates as well as extra costly
      heteroatom-containing organic precursors. Additionally, isolation of rock salts
      is an extra bonus of present work. The technique is simple, but successful,
      offering naturally doped conductive hierarchical porous URC, which leads to
      superior electrocatalytic ORR activity comparable to state of the art Pt/C
      catalyst along with much improved durability and methanol tolerance,
      demonstrating that the URC can be a promising alternative to costly Pt-based
      electrocatalyst for ORR. The ORR activity can be addressed in terms of heteroatom
      doping, surface properties and electrical conductivity of the carbon framework. 

PMID- 24909134
TI  - The pathogenesis of Pisa syndrome in Parkinson's disease.
AB  - Postural abnormalities such as postural deviations affect nearly all patients
      with advanced Parkinson's disease and represent an important source of
      disability. Although their existence has long been known, their management
      remains a challenge as they respond poorly to medication, brain surgery, or
      physiotherapy. Improving management strategies will require better understanding
      of the mechanisms underlying such postural deformities. In this review on the
      pathophysiology of Pisa syndrome, we examine the data supporting the central and
      peripheral hypotheses that attempt to explain these lateral trunk deviations.
      Although the pathophysiology is very probably multifactorial, the bulk of the
      data supports central, rather than peripheral, hypotheses. The central hypotheses
      that are best supported by both animal studies and clinical data include
      asymmetry of basal ganglia output and abnormalities in the central integration of
      sensory information. Further studies are needed to elucidate the pathophysiology
      underlying Pisa syndrome.

PMID- 24909135
TI  - Analyzing risk factors for early postoperative bile leakage based on Clavien
      classification in bile duct stones.
AB  - OBJECTIVES: To identify the risk factors of bile leakage, with different
      severity, based on Clavien-Dindo complication classification system. MATERIALS
      AND METHODS: A retrospective analysis of 943 eligible patients was performed.
      Sixty-eight patients, with bile leakage, were divided into 2 groups: mild bile
      leakage (grades I, II, n = 41) and severe bile leakage (grades III, IV, V, n =
      27). Twenty-five potential factors were analyzed, by multivariate regression
      analyses, to identify independent risk factors of bile leakage. RESULTS: The
      independent risk factors of bile leakage, for the entire cohort, included attacks
      of acute cholangitis within 1 month, associated biliary-enteric anastomosis
      (BEA), associated hepatectomy and previous biliary surgery. The independent risk
      factors for patients with mild bile leakage were attacks of acute cholangitis
      within 1 month, associated hepatectomy, and a history of previous biliary
      surgery. Similarly, the independent risk factors for patients with severe bile
      leakage were attacks of acute cholangitis within 1 month, associated hepatectomy,
      and associated BEA. CONCLUSIONS: Risk factors for mild and severe postoperative
      bile leakage, in bile duct stones, were different.

PMID- 24909136
TI  - Hilar cholangiocarcinoma in cirrhotic liver: a case-control study.
AB  - BACKGROUND: Surgical resection is the only hope for patients with
      cholangiocarcinoma (CC). This study is designed to assess the impact of cirrhosis
      on the outcome of surgical management for CC. PATIENT AND METHODS: We
      retrospectively studied all patients who underwent surgical resection for hilar
      CC. Group I (patients with cirrhotic liver) and Group II (patients with non
      cirrhotic liver). Preoperative demographic data, intra-operative data, and
      postoperative details were collected. RESULTS: Only 102/243 patients (41.9%) had
      cirrhotic liver. Caudate lobe resection was more frequently performed in the non
      cirrhotic group (P = <0.001). There was no difference between both groups
      regarding intraoperative blood loss and the need for blood transfusion. The
      median postoperative stay was higher in the cirrhotic group (P = 0.063). The
      incidence of early postoperative liver cell failure was significantly higher in
      the cirrhotic group (P = <0.001). Cirrhosis was associated with significantly
      lower overall survival (P = <0.001). CONCLUSION: Patients with concomitant liver
      cirrhosis and hilar CC should not be precluded from surgical resection and should
      be considered for resection at high volume centers with expertise available to
      manage liver cirrhosis. The incidence of early postoperative liver cell failure
      was significantly higher in the cirrhotic group.

PMID- 24909137
TI  - Surgical and procedural skills training at medical school - a national review.
AB  - This national study quantifies procedural and surgical skills training at medical
      schools in the United Kingdom (UK), a stipulated requirement of all graduates by
      the General Medical Council (GMC). A questionnaire recorded basic procedural and
      surgical skills training provided by medical schools and surgical societies in
      the UK. Skills were extracted from (1) GMC Tomorrows Doctors and (2) The Royal
      College of Surgeons Intercollegiate Basic Surgical Skills (BSS) course. Data from
      medical school curricula and extra-curricular student surgical societies were
      compared against the national GMC guidelines and BSS course content. Data were
      analysed using Mann-Whitney U tests. Representatives from 23 medical schools
      completed the survey (71.9% response). Thirty one skills extracted from the BSS
      course were split into 5 categories, with skills content cross referenced against
      GMC documentation. Training of surgical skills by medical schools was as follows:
      Gowning and gloving (72.8%), handling instruments (29.4%), knot tying (17.4%),
      suturing (24.7%), other surgical techniques (4.3%). Surgical societies provided
      significantly more training of knot tying (64.4%, P = 0.0013) and suturing
      (64.5%, P = 0.0325) than medical schools. Medical schools provide minimal basic
      surgical skills training, partially supplemented by extracurricular student
      surgical societies. Our findings suggest senior medical students do not possess
      simple surgical and procedural skills. Newly qualified doctors are at risk of
      being unable to safely perform practical procedures, contradicting GMC
      Guidelines. We propose a National Undergraduate Curriculum in Surgery and
      Surgical Skills to equip newly qualified doctors with basic procedural skills to
      maximise patient safety.

PMID- 24909138
TI  - Current therapeutic prospectives in the functional rehabilitation of vocal fold
      paralysis after thyroidectomy: CO2 laser aritenoidectomy.
AB  - A frequent complication of thyroid surgery is laryngeal nerve palsy with
      transitory or permanent deficiency of cordal motility. Peripheral mono-or
      bilateral palsy in these cases may either occur, in adduction or abduction, and
      be complete or not complete. Bilateral vocal cords paralysis cause a persistent
      dyspnoic symptomatology with worsening during physical exercise or flogistic
      episodes of the upper airway: true vocal cords adduction, in median or paramedian
      position reduce the glottic space and increases respiratory resistances. Several
      surgical procedures have been proposed for the treatment of respiratory distress
      secondary to bilateral cord palsy. The aim of this study is to value the role of
      CO2 laser aritenoidectomy in 93 patients affected by bilateral paralysis in
      adduction of true vocal cords. Pre and postoperative evaluations included
      clinical results, spirometry, aerodynamics studies and evaluation of foniatric
      performance (MPT, H/N Ratio, Jitter and Shimmer) with a mean follow-up of 12
      years. CO2 laser aritenoidectomy induces a complete resolution of respiratory
      failure, maintaining a good vocal quality, minimum surgical stress with low
      percentage of complications and a short hospitalization. 

PMID- 24909139
TI  - EGFL7 is expressed in bone microenvironment and promotes angiogenesis via ERK,
      STAT3, and integrin signaling cascades.
AB  - Angiogenesis plays a pivotal role in bone formation, remodeling, and fracture
      healing. The regulation of angiogenesis in the bone microenvironment is highly
      complex and orchestrated by intercellular communication between bone cells and
      endothelial cells. Here, we report that EGF-like domain 7 (EGFL7), a member of
      the epidermal growth factor (EGF) repeat protein superfamily is expressed in both
      the osteoclast and osteoblast lineages, and promotes endothelial cell activities.
      Addition of exogenous recombinant EGFL7 potentiates SVEC (simian virus 40
      transformed mouse microvascular endothelial cell line) cell migration and tube
      like structure formation in vitro. Moreover, recombinant EGFL7 promotes
      angiogenesis featuring web-like structures in ex vivo fetal mouse metatarsal
      angiogenesis assay. We show that recombinant EGFL7 induces phosphorylation of
      extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducer and
      activator of transcription 3 (STAT3), and focal adhesion kinase (FAK) in SVEC
      cells. Inhibition of ERK1/2 and STAT3 signaling impairs EGFL7-induced endothelial
      cell migration, and angiogenesis in fetal mouse metatarsal explants.
      Bioinformatic analyses indicate that EGFL7 contains a conserved RGD/QGD motif and
      EGFL7-induced endothelial cell migration is significantly reduced in the presence
      of RGD peptides. Moreover, EGFL7 gene expression is significantly upregulated
      during growth plate injury repair. Together, these results demonstrate that EGFL7
      expressed by bone cells regulates endothelial cell activities through integrin
      mediated signaling. This study highlights the important role that EGFL7, like
      EGFL6, expressed in bone microenvironment plays in the regulation of angiogenesis
      in bone.

PMID- 24909140
TI  - Remission with fingolimod in a case of demyelinating polyneuropathy.

PMID- 24909141
TI  - Multiwalled carbon nanotube-modified poly(D,L-lactide-co-glycolide) scaffolds for
      dendritic cell load.
AB  - Poly(D,L-lactide-co-glycolide) (PLGA) is widely used in a variety of tissue
      engineering and drug delivery applications due to its biodegradability and
      biocompatibility. But PLGA surfaces are usually hydrophobic which limited the
      loading and seeding capacities for cells, especially semiadherent immune cells.
      In this paper we described an attempt to improve the hydrophilicity and surface
      architecture for accommodating dendritic cells (DCs) that are widely used as
      professional antigen presenting cells in immune therapy of cancer and other
      diseases. The 3D porous PLGA scaffold was made by solvent casting/salt leaching
      of PLGA blended with surface functionalized multiwalled carbon nanotubes (F
      MWCNTs). The incorporation and dispersion of F-MWCNT in the scaffold structures
      resulted in not only improved surface hydrophilicity but also nanoscale surface
      structure that would provide a preferable microenvironment for DCs attachment. We
      think such a scaffold material may be more desirable for immune cell delivery for
      immunotherapy.

PMID- 24909142
TI  - Water-soluble triarylboron compound for ATP imaging in vivo using analyte-induced
      finite aggregation.
AB  - Adenosine 5'-triphosphate (ATP) is a multifunctional molecule that participates
      in many important biological processes. Currently, fluorescence indicators for
      ATP with high performance are in demand. Reported herein is a novel water-soluble
      triarylboron compound which displays an apparent ATP-dependent fluorescence
      enhancement when dispersed in water. It can selectively recognize ATP from other
      bioactive substances in vitro and in vivo. The ATP-induced finite aggregation
      endows the indicator with appreciable photostability and superior tolerance to
      environmental electrolytes. This indicator has been successfully applied to the
      ATP imaging in NIH/3T3 fibroblast cells. The difference in the ATP levels within
      the membrane and cytosol is clearly visible. 

PMID- 24909143
TI  - Long-term impact of neonatal inflammation on demyelination and remyelination in
      the central nervous system.
AB  - Perinatal inflammation causes immediate changes of the blood-brain barrier (BBB)
      and thus may have different consequences in adult life including an impact on
      neurological diseases such as demyelinating disorders. In order to determine if
      such a perinatal insult affects the course of demyelination in adulthood as
      "second hit," we simulated perinatal bacterial inflammation by systemic
      administration of lipopolysaccharide (LPS) to either pregnant mice or newborn
      animals. Demyelination was later induced in adult animals by cuprizone
      [bis(cyclohexylidenehydrazide)], which causes oligodendrocyte death with
      subsequent demyelination accompanied by strong microgliosis and astrogliosis. A
      single LPS injection at embryonic day 13.5 did not have an impact on
      demyelination in adulthood. In contrast, serial postnatal LPS injections (P0-P8)
      caused an early delay of myelin removal in the corpus callosum, which was
      paralleled by reduced numbers of activated microglia. During remyelination,
      postnatal LPS treatment enhanced early remyelination with a concomitant increase
      of mature oligodendrocytes. Furthermore, the postnatal LPS challenge impacts the
      phenotype of microglia since an elevated mRNA expression of microglia related
      genes such as TREM 2, CD11b, TNF-alpha, TGF-beta1, HGF, FGF-2, and IGF-1 was
      found in these preconditioned mice during early demyelination. These data
      demonstrate that postnatal inflammation has long-lasting effects on microglia
      functions and modifies the course of demyelination and remyelination in
      adulthood.

PMID- 24909144
TI  - Size dependence of ultrafast charge dynamics in monodisperse Au nanoparticles
      supported on TiO2 colloidal spheres.
AB  - Sub-nanosecond charge dynamics in monodisperse Au nanoparticles (NPs) supported
      on TiO2 colloidal spheres are studied as a function of NP diameter using
      ultrafast transient absorption spectroscopy. The decay of the transmittance
      changes observed in the region of the plasmon resonance of the Au NPs following
      photoexcitation of the TiO2 spheres are well-described by a bi-exponential
      function consisting of a fast component of 2 ps duration associated with electron
      phonon scattering, followed by a slow and relatively weak component associated
      with phonon-phonon scattering. The decay constant characterising the latter
      component was found to be dependent on the size of the Au NPs, rising from 49 +/-
      3 to 128 +/- 6 ps as the diameter of the Au NPs increased from 12.2 +/- 2.2 nm to
      24.5 +/- 2.8 nm, respectively. 

PMID- 24909146
TI  - Acne vulgaris: an inflammatory disease even before the onset of clinical lesions.
AB  - Acne is a chronic self-limited disease, which affects mostly teenagers, without
      gender difference. In recent years, the incidence has increased in female adults.
      The factors involved in this epidemiological observation are still under
      discussion in the literature. Clinically, acne is characterized by different
      types of lesions. The disease affects the regions rich in sebaceous glands (face,
      chest and upper back). The clinical lesions are: open and closed comedones,
      erythematous papules, pustules, nodules and different types of scars. Taking into
      consideration the general concept of inflammation (redness, pain, heat and loss
      of function), acne is traditionally classified as non-inflammatory (open and
      closed comedones) and inflammatory (other primary lesions). With the knowledge
      advancement this concept seems to be wrong and therefore acne would be an
      inflammatory disease even before the onset of their clinical lesions.

PMID- 24909145
TI  - Semi-continuous, label-free immunosensing approach for Ca2+-based conformation
      change of a calcium-binding protein.
AB  - A label-free immunosensing method based on the conformational change of calcium
      binding protein (CBP) depending on analyte concentration was explored for semi
      continuous analysis of free Ca(2+). Glucose-galactose-binding protein as a CBP
      and produced as a recombinant protein by Escherichia coli was used as the
      immunogen to produce monoclonal antibodies by hybridoma technology. We finally
      screened the 3-6F cell clone, which produced the desired antibody specific to a
      particular structural conformation of the protein that occurred only upon CBP
      calcium complex formation. To construct an immunosensor, the antibody was
      immobilized via a secondary antibody on an Octet Red optical fiber-based label
      free sensor. Calcium analysis was conducted on the sensor in combination with CBP
      previously added to the aqueous sample, which distinguished the sensor signal
      according to the analyte concentration. The immunosensor produced a signal in
      real time with a response time of approximately 15 min and could be reused for
      analyses of different samples in a semi-continuous manner. The minimum detection
      limit of the analyte under optimal conditions was 0.09 mM and the upper limit was
      about 5 mM (log-logit transformed standard curve linearity: R(2) > 98%). In
      sample tests with milk, the analytical performance of the sensor was highly
      correlated (R(2) > 99%) with that of the reference system based on the KMnO4
      titration method (ISO 12081). Although the sensor showed cross-reactivity at high
      concentrations (>1 mM) of cations including zinc, iron, manganese, and copper,
      these ionic components were not traceable (<0.01 mM) in milk. 

PMID- 24909147
TI  - Paclitaxel formulations: challenges and novel delivery options.
AB  - Paclitaxel (PTX), a taxane plant product, is one of the most effective broad
      spectrum anti-cancer agents and approved for the treatment of a variety of
      cancers including ovarian, breast, lung, head and neck as well as Kaposi's
      sarcoma. Poor aqueous solubility and serious side effects associated with
      commercial preparation of PTX (Taxol(r)) triggered the development of alternative
      PTX formulations. Over past three decades, plethora of research work has been
      published towards the development of cremophor free and efficient formulations.
      Various nanocarrier systems including nanoparticles, liposomes, micelles,
      bioconjugates and dendrimers have been employed in order to improve PTX
      solubility and eliminate undesired side effects. These nanocarriers offer the
      advantage of high degree of encapsulation and cellular uptake, escape from
      elimination by P-glycoprotein (P-gp) mediated efflux, and can be explored for
      targeted drug delivery. The potential of these nanocarriers is reflected by the
      fact that various nanocarriers of PTX are in different stages of clinical trials
      and a few have already been commercialized including Abraxane(r), Lipusu and
      Genexol PM(r). This review focuses on the various challenges associated with PTX
      formulation development, limitations of existing formulations and novel
      approaches for the development of alternative formulations for PTX and also
      highlights the development of novel formulations in clinical settings. 

PMID- 24909148
TI  - Effect of combination of acrylic polymers on the release of nevirapine formulated
      as extended release matrix pellets using extrusion and spheronization technique.
AB  - The aim of the present research work was to formulate and evaluate the extended
      release matrix pellets of nevirapine using extrusion and spheronization technique
      which will be an alternative technique for making extended release dosage forms
      and to compare the drug release profiles of the formulations with the reference
      product. In vitro dissolutions were carried out in 0.04M Phosphate buffer pH 6.8
      with 2% w/v SLS (sodium lauryl sulphate) for 24 hours with USP type I apparatus
      at 75rpm. The drug release from the optimised formulation was comparable to that
      of the reference product and follows first order kinetics followed by non-fickian
      transport mechanism of drug release which confirms the drug release pattern
      involves complex mixture of diffusion and erosion. The similarity factor, f2
      value of optimised formulation was found to be 70, which shows that the developed
      formulation was comparable to that of the reference product. 

PMID- 24909149
TI  - Poly(ethylene glycol)-block-poly(epsilon-caprolactone) nanomicelles for the
      solubilization and enhancement of antifungal activity of sertaconazole.
AB  - Sertaconazole nitrate is a broad spectrum imidazole antifungal agent with
      antibacterial and anti-inflammatory properties. However, its lipophilic nature
      and very poor aqueous solubility limit its use in the clinic. The aim of this
      study was to develop and characterize poly(ethylene glycol)-block-poly(epsilon
      caprolactone) (PEG-b-PCL) polymeric nanomicelles for the solubilization and
      enhancement of sertaconazole antifungal activity. Sertaconazole was incorporated
      into PEG-b- PCL polymeric nanomicelles by a co-solvent evaporation method and
      micelle size, drug loading capacity and drug release properties were determined.
      The antifungal properties of nanomicelle-loaded drug were evaluated in Fusarium
      miscanthi, Microsporum canis, and Trichophyton mentagrophytes isolated,
      respectively from fungal keratitis, ringworm, and tinea corporis. PEG-b-PCL
      formed nanomicelles in aqueous solution with a diameter ranging from 40-80 nm,
      depending on the polymer composition and level of drug loading. Drug loading
      properties of the nanomicelles were dependent on the PCL block molecular weight
      and drug/polymer weight feed ratio. Drug encapsulation efficiency of up to 85%
      was achieved and this resulted in more than 80-fold enhancement in sertaconazole
      aqueous solubility at polymer concentration of 0.2%. Drug release studies showed
      an initial burst release followed by sustained drug release for 72 hours. In
      vitro antimycotic studies showed that nanomicelle-incorporated sertaconazole
      inhibited fungal growth in a concentration dependent manner. Further, it was more
      effective than the free drug in inhibiting the growth of Fusarium miscanthi and
      Microsporum canis. These results confirm the utility of PEG-b-PCL nanomicelles in
      enhancing the aqueous solubility and antifungal activity of sertaconazole or
      other similar antifungal drugs. 

PMID- 24909150
TI  - Graphene and graphene oxide as a docking station for modern drug delivery system.
AB  - Motivated by the success and exhaustive research on carbon nanotubes (CNTs) based
      drug delivery, graphene, a two-dimensional; honey-comb crystal lattice has
      emerged as the rising star in recent years. Graphene is a flat monolayer of
      carbon atoms that holds many promising properties such as unparalleled thermal
      conductivity, remarkable electronic properties, and most intriguingly higher
      planar surface and superlative mechanical strength, which are attractive in
      biotechnological applications. Delivery of anti-cancer drugs using graphene and
      its derivatives has sparked major interest in this emerging field. The anti
      cancer therapies often pose a limitation of insolubility, administration problems
      and cell penetration ability. In addition, systemic toxicity caused by lack of
      selective targeting towards cancer cells and inefficient distribution limits its
      clinical applications. Graphene nanocomposite is a promising tool to address
      these drawbacks. This review will focus on various synthesis and
      functionalization of graphene and graphene oxide for providing better solubility
      and targeted drug delivery at cancer cells. A more advanced and 'smart' graphene
      hybrid nanostructures that have several functionalities such as stimulus-response
      mediated delivery, imaging at release sites as well as transfection into cancer
      cells are also presented. A brief description on the challenges and perspectives
      for future research in this field is also discussed.

PMID- 24909151
TI  - Barriers and facilitators for participation in health promotion programs among
      employees: a six-month follow-up study.
AB  - BACKGROUND: Health promotion programs (HPPs) are thought to improve health
      behavior and health, and their effectiveness is increasingly being studied.
      However, participation in HPPs is usually modest and effect sizes are often
      small. This study aims to (1) gain insight into the degree of participation of
      employees in HPPs, and (2) identify factors among employees that are associated
      with both their intention to participate and actual participation in HPPs.
      METHODS: Employees of two organizations were invited to participate in a six
      month follow-up study (n = 744). Using questionnaires, information on
      participation in HPPs was collected in two categories: employees' intention at
      baseline to participate and their actual participation in a HPP during the follow
      up period. The following potential determinants were assessed at baseline: social
      cognitive factors, perceived barriers and facilitators, beliefs about health at
      work, health behaviors, and self-perceived health. Logistic regression analyses,
      adjusted for demographics and organization, were used to examine associations
      between potential determinants and intention to participate, and to examine the
      effect of these determinants on actual participation during follow-up. RESULTS:
      At baseline, 195 employees (26%) expressed a positive intention towards
      participation in a HPP. During six months of follow-up, 83 employees (11%)
      actually participated. Participants positively inclined at baseline to
      participate in a HPP were more likely to actually participate (OR = 3.02, 95% CI:
      1.88-4.83). Privacy-related barriers, facilitators, beliefs about health at work,
      social-cognitive factors, and poor self-perceived health status were
      significantly associated with intention to participate. The odds of employees
      actually participating in a HPP were higher among participants who at baseline
      perceived participation to be expected by their colleagues and supervisor (OR =
      2.87, 95% CI: 1.17-7.02) and among those who said they found participation
      important (OR = 2.81, 95% CI: 1.76-4.49). CONCLUSIONS: Participation in HPPs
      among employees is limited. Intention to participate predicted actual
      participation in a HPP after six months of follow-up. However, only 21% of
      employees with a positive intention actually participated during follow-up.
      Barriers, facilitators, beliefs about health at work, social-cognitive factors,
      and a poor self-perceived health status were associated with intention to
      participate, but hardly influenced actual participation during follow-up.

PMID- 24909152
TI  - Real-time prediction of respiratory motion using a cascade structure of an
      extended Kalman filter and support vector regression.
AB  - The motion of thoracic and abdominal tumours induced by respiratory motion often
      exceeds 20 mm, and can significantly compromise dose conformality. Motion
      adaptive radiotherapy aims to deliver a conformal dose distribution to the tumour
      with minimal normal tissue exposure by compensating for the tumour motion. This
      adaptive radiotherapy, however, requires the prediction of the tumour movement
      that can occur over the system latency period. In general, motion prediction
      approaches can be classified into two groups: model-based and model-free. Model
      based approaches utilize a motion model in predicting respiratory motion. These
      approaches are computationally efficient and responsive to irregular changes in
      respiratory motion. Model-free approaches do not assume an explicit model of
      motion dynamics, and predict future positions by learning from previous
      observations. Artificial neural networks (ANNs) and support vector regression
      (SVR) are examples of model-free approaches. In this article, we present a
      prediction algorithm that combines a model-based and a model-free approach in a
      cascade structure. The algorithm, which we call EKF-SVR, first employs a model
      based algorithm (named LCM-EKF) to predict the respiratory motion, and then uses
      a model-free SVR algorithm to estimate and correct the error of the LCM-EKF
      prediction. Extensive numerical experiments based on a large database of 304
      respiratory motion traces are performed. The experimental results demonstrate
      that the EKF-SVR algorithm successfully reduces the prediction error of the LCM
      EKF, and outperforms the model-free ANN and SVR algorithms in terms of prediction
      accuracy across lookahead lengths of 192, 384, and 576 ms. 

PMID- 24909154
TI  - Evaluation of airway dimensions and changes in hyoid bone position following
      class II functional therapy with activator.
AB  - AIM: The aim of this study was to evaluate the long-term effects of Class 2
      functional treatment on airway dimensions and positional changes in hyoid bone
      and compare it with that of an untreated Class 2 control group. METHODS: Lateral
      cephalograms of 16 patients (eight girls, eight boys, mean chronological age =
      11.36 +/- 0.77 years) who were treated with activator and 19 patients (11 girls,
      eight boys, mean chronological age = 12.14 +/- 0.65 years) who served as control
      were used for linear, angular and area measurements regarding airway track and
      hyoid bone. Statistics. Intra-group comparisons were performed by paired t-test
      and Wilcoxon test, whereas independent t-test and Mann Whitney-U were used for
      inter-group comparisons. RESULTS: During treatment (T2-T1), nasopharyngeal height
      and nasopharyngeal area increased (p < 0.05) and hyoid bone moved downward (H-SN;
      p < 0.001) and forward (H-C3; p < 0.01). During retention period (T3-T2);
      nasopharyngeal (p < 0.01) and oropharyngeal area increased (p < 0.05). H-SN (p <
      0.01) and C3-H distances (p < 0.05) increased. Hyoid bone position exhibited
      significant changes (H-SN, p < 0.001; C3-H, p < 0.01). The increases in C3-H in
      long-term was more in the activator group than control (p < 0.05). CONCLUSIONS:
      In growing Class 2 patients with mandibular deficiency and airway track without
      obstructions, functional appliance treatment provided favorable effects on
      nasopharyngeal and oropharyngeal area throughout the retention period.

PMID- 24909153
TI  - Ontology-supported research on vaccine efficacy, safety and integrative
      biological networks.
AB  - While vaccine efficacy and safety research has dramatically progressed with the
      methods of in silico prediction and data mining, many challenges still exist. A
      formal ontology is a human- and computer-interpretable set of terms and relations
      that represent entities in a specific domain and how these terms relate to each
      other. Several community-based ontologies (including Vaccine Ontology, Ontology
      of Adverse Events and Ontology of Vaccine Adverse Events) have been developed to
      support vaccine and adverse event representation, classification, data
      integration, literature mining of host-vaccine interaction networks, and analysis
      of vaccine adverse events. The author further proposes minimal vaccine
      information standards and their ontology representations, ontology-based linked
      open vaccine data and meta-analysis, an integrative One Network ('OneNet') Theory
      of Life, and ontology-based approaches to study and apply the OneNet theory. In
      the Big Data era, these proposed strategies provide a novel framework for
      advanced data integration and analysis of fundamental biological networks
      including vaccine immune mechanisms. 

PMID- 24909155
TI  - Randomized controlled clinical trial on the efficacy of dentin desensitizing
      agents.
AB  - OBJECTIVE: To investigate the effects of four dentin desensitizers on pain
      reduction in hypersensitive cervical dentin lesions. MATERIALS AND METHODS: The
      trial was designed as a randomized, controlled, four-arm, single-masked study.
      Fifty subjects with at least one hypersensitive lesion in each of the four
      quadrants were allocated. The requested pre-operative pain, determined as a
      response to 2-s air-blast (AB) and probe scratching (PS), was >=5 on a VAS scale,
      0 = no through to 10 = worst pain. Randomly each subject received each of the
      four treatments: MS Coat One F (MSC, Sun Medical, Japan), Nanoseal (NAN, Nishin,
      Japan), Teethmate Desensitizer (TMD, Kuraray Noritake, Japan) and Gluma
      Desensitizer PowerGel (GLU, HeraeusKulzer, Germany). The investigator assessed
      blindly the pain response using the two stimuli and recorded the patients' VAS
      scores before and immediately after application, after 1 week and after 1, 3 and
      6 months. STATISTICAL DATA TREATMENT: ANOVA and post-hoc testing (p <= 0.05).
      RESULTS: Forty-nine subjects completed the trial. Pre-operative dentin
      hypersensitivity (DH) for the groups was not significantly different. All
      desensitizers reduced DH significantly throughout the 6-months observation. ANOVA
      revealed significant differences among VAS scores, obtained with the
      desensitizing agents (p < 0.001). Ranking by post-hoc testing was: MSC > NAN >
      TMD > GLU (p < 0.05). Upon PS NAN and TMD showed slight but significant regain of
      sensitivity after 6 months. For GLU PS scores immediately after application and
      after 6 months were not significantly different, whereas recalls after 1 week, 1
      month and 3 months revealed significantly lower scores. CONCLUSION: The calcium
      phosphate-based TMD and GLU proved highly effective in reducing sensitivity.

PMID- 24909156
TI  - Pneumatic tube-transported blood samples in lithium heparinate gel separator
      tubes may be more susceptible to haemolysis than blood samples in serum tubes.
AB  - Pneumatic tube systems are widely used in hospitals. Advantages are high speed
      and rapid availability of the samples. However, the transportation by pneumatic
      tube promotes haemolysis. Haemolysis interferes with many spectrophotometric
      assays and is a common problem in clinical laboratories. The haemolysis index
      (HI) as a semi-quantitative representation of the level of haemolysis was
      compared in unpaired tube-transported and hand-delivered routine lithium
      heparinate plasma samples (n = 1368 and n = 837, respectively). Additionally, the
      HI distribution was measured in lithium heparinate plasma samples with a HI above
      the threshold value of 20 and in paired serum samples after transportation by
      pneumatic tube system. HI values above 20 can interfere with the selected assays:
      Creatine kinase (CK), creatine kinase-MB (CK-MB) and alanine aminotransferase
      (ALT) activities. These parameters were determined to demonstrate how haemolysis
      affects the results. 17.5% of the tube-transported plasma samples and 2.6% of the
      hand-delivered plasma samples had a HI above 20. The median HI in pneumatic tube
      transported lithium heparinate plasma was 85 and 33 in the paired serum samples.
      The median HI difference between paired plasma and serum was 46. Blood samples in
      lithium heparinate tubes may be substantially more susceptible to haemolysis by
      pneumatic tube transportation than serum tube samples. Although our results
      cannot be universally applied to laboratories with different pneumatic tube
      systems, it is recommended that each laboratory evaluate carefully the degree of
      haemolysis after the transportation by the own pneumatic tube system and in terms
      of the sample type.

PMID- 24909157
TI  - Allowable systematic difference between two instruments measuring the same
      analyte.
AB  - BACKGROUND: If a laboratory has two analytical instruments for measuring the
      concentration of the same analyte and samples from the patients are randomly
      allocated to either of the two, then an allowable systematic difference between
      the two instruments should be defined. We present a solution to this problem,
      based on the traditional criterion that the total analytical standard deviation
      (SD) shall be less than half the within-subject biological SD. METHODS: We
      derived a formula for estimating the SD of the distribution of analytical results
      that may stem from two instruments with different means and SDs and different
      probabilities of being used. The formula was used to estimate the allowable
      systematic difference between the two instruments. RESULTS: The allowable
      systematic difference depends on the within-subject biological SD, the SDs of the
      two instruments, and the probability that a sample is analyzed with a certain
      instrument. When this probability is 0.5, the allowable systematic difference
      approaches the magnitude of the within-subject biological SD as the analytical
      SDs approach zero, while no systematic difference is allowed when the two
      analytical SDs are equal to their maximum allowable value of half the within
      subject biological SD. CONCLUSIONS: In a monitoring situation, the allowable
      systematic difference between two analytical instruments depends on the
      probability that a sample is allocated to each of the instruments as well as the
      analytical SDs and the within-subject biological SD.

PMID- 24909158
TI  - Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex
      concentrate: a Sonoclot in vitro study.
AB  - OBJECTIVE: Dabigatran is a new oral direct thrombin inhibitor. No specific
      antidote exists in the event of hemorrhage, but prothrombin complex concentrate
      (PCC) and recombinant activated factor VII (rFVIIa) are suggested therapies.
      Sonoclot is a bedside viscoelastic instrument for monitoring the coagulation
      process in whole blood. The aim of this study was to investigate the effect of
      dabigatran and reversal with PCC and rFVIIa, as monitored by the Sonoclot.
      METHODS: Citrated whole blood was drawn and mixed in vitro with dabigatran,
      dabigatran + PCC or dabigatran + rFVIIa and analyzed with three different
      Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated.
      RESULTS: The Sonoclot detected in vitro-induced anticoagulation due to dabigatran
      with the glassbead- and kaolin-activated cuvettes. There was no reversing effect
      of PCC, probably due to the presence of heparin in the PCC we used. There was no
      certain reversing effect of rFVIIa. CONCLUSIONS: The Sonoclot can detect the
      anticoagulant effect of dabigatran. Our results do not support efficient reversal
      of dabigatran with PCC and rFVIIa, or alternatively do not support the ability of
      Sonoclot to detect a reversing effect of the PCC and rFVIIa in our study.
      Clinical studies of dabigatran-treated patients with severe bleeding are called
      for, as well as the continued development of specific antidotes and monitoring
      techniques.

PMID- 24909159
TI  - Differential developmental requirement and peripheral regulation for dermal
      Vgamma4 and Vgamma6T17 cells in health and inflammation.
AB  - Dermal IL-17-producing gammadeltaT cells have a critical role in skin
      inflammation. However, their development and peripheral regulation have not been
      fully elucidated. Here we demonstrate that dermal gammadeltaT cells develop from
      the embryonic thymus and undergo homeostatic proliferation after birth with
      diversified TCR repertoire. Vgamma6T cells are bona fide resident, but precursors
      of dermal Vgamma4T cells may require extrathymic environment for imprinting skin
      homing properties. Thymic Vgamma6T cells are more competitive than Vgamma4 for
      dermal gammadeltaT cell reconstitution and TCRdelta(-/-) mice reconstituted with
      Vgamma6 develop psoriasis-like inflammation after IMQ-application. Although both
      IL-23 and IL-1beta promote Vgamma4 and Vgamma6 proliferation, Vgamma4 are the
      main source of IL-17 production that requires IL-1 signalling. Mice with
      deficiency of IL-1RI signalling have significantly decreased skin inflammation.
      These studies reveal a differential developmental requirement and peripheral
      regulation for dermal Vgamma6 and Vgamma4 gammadeltaT cells, implying a new
      mechanism that may be involved in skin inflammation. 

PMID- 24909160
TI  - Stem cell programs are retained in human leukemic lymphoblasts.
AB  - Leukemic lymphoblasts within different immunophenotypic populations possess stem
      cell properties. However, whether or not the self-renewal program is retained
      from stem cells or conferred on progenitors by leukemogenic molecules remains
      unknown. We have addressed the issue in the context of TEL-AML1-associated acute
      lymphoblastic leukemia (ALL) by profiling a refined program edited from genes
      essential for self-renewal of hematopoietic stem cells and B-cell development.
      Bioinformatic analysis shows that ALL populations are loosely clustered and close
      to the normal population that contains stem and primitive progenitor cells. This
      finding indicates that immunophenotypes do not reflect maturation stages in ALL
      and that the self-renewal program may be retained from stem cells. Results of
      assessing 'first hit' function of TEL-AML1 in different populations of normal
      cells demonstrate the molecular model. Therefore, the current study shows a
      leukemogenic scenario of human ALL in which programs of stem cells are sustained
      in distinct fractions by leukemogenic mutations.

PMID- 24909163
TI  - Epigenetics in radiation-induced fibrosis.
AB  - Radiotherapy is a major cancer treatment option but dose-limiting side effects
      such as late-onset fibrosis in the irradiated tissue severely impair quality of
      life in cancer survivors. Efforts to explain radiation-induced fibrosis, for
      example, by genetic variation remained largely inconclusive. Recently published
      molecular analyses on radiation response and fibrogenesis showed a prominent role
      of epigenetic gene regulation. This review summarizes the current knowledge on
      epigenetic modifications in fibrotic disease and radiation response, and it
      points out the important role for epigenetic mechanisms such as DNA methylation,
      microRNAs and histone modifications in the development of this disease. The
      synopsis illustrates the complexity of radiation-induced fibrosis and reveals the
      need for investigations to further unravel its molecular mechanisms. Importantly,
      epigenetic changes are long-term determinants of gene expression and can
      therefore support those mechanisms that induce and perpetuate fibrogenesis even
      in the absence of the initial damaging stimulus. Future work must comprise the
      interconnection of acute radiation response and long-lasting epigenetic effects
      in order to assess their role in late-onset radiation fibrosis. An improved
      understanding of the underlying biology is fundamental to better comprehend the
      origin of this disease and to improve both preventive and therapeutic strategies.

PMID- 24909161
TI  - The ets transcription factor Fli-1 in development, cancer and disease.
AB  - Friend leukemia virus-induced erythroleukemia-1 (Fli-1), an E26 transformation
      specific (ETS) transcription factor, was isolated a quarter century ago through a
      retrovirus mutagenesis screen. Fli-1 has since been recognized to play critical
      roles in normal development and homeostasis. For example, it transcriptionally
      regulates genes that drive normal hematopoiesis and vasculogenesis. Indeed, Fli-1
      is one of 10 key regulators of hematopoietic stem/progenitor cell maintenance and
      differentiation. Aberrant expression of Fli-1 also underlies a number of virally
      induced leukemias, including Friend virus-induced erythroleukemia and various
      types of human cancers, and it is the target of chromosomal translocations in
      childhood Ewing's sarcoma. Abnormal expression of Fli-1 is important in the
      etiology of autoimmune diseases such as systemic lupus erythematosus and systemic
      sclerosis. These studies establish Fli-1 as a strong candidate for drug
      development. Despite difficulties in targeting transcription factors, recent
      studies identified small-molecule inhibitors for Fli-1. Here we review past and
      ongoing research on Fli-1 with emphasis on its mechanistic function in autoimmune
      disease and malignant transformation. The significance of identifying Fli-1
      inhibitors and their clinical applications for treatment of disease and cancer
      with deregulated Fli-1 expression are discussed.

PMID- 24909162
TI  - Targeted resequencing of the microRNAome and 3'UTRome reveals functional germline
      DNA variants with altered prevalence in epithelial ovarian cancer.
AB  - Ovarian cancer is a major cause of cancer deaths, yet there have been few known
      genetic risk factors identified, the best known of which are disruptions in
      protein coding sequences (BRCA1 and 2). Recent findings indicate that there are
      powerful genetic markers of cancer risk outside of these regions, in the
      noncoding mRNA control regions. To identify additional cancer-associated,
      functional non-protein-coding sequence germline variants associated with ovarian
      cancer risk, we captured DNA regions corresponding to all validated human
      microRNAs and the 3' untranslated regions (UTRs) of ~6000 cancer-associated genes
      from 31 ovarian cancer patients. Multiple single-nucleotide polymorphisms in the
      3'UTR of the vascular endothelial growth factor receptor/FLT1, E2F2 and PCM1
      oncogenes were highly enriched in ovarian cancer patients compared with the 1000
      Genome Project. Sequenom validation in a case-control study (267 cases and 89
      controls) confirmed a novel variant in the PCM1 3'UTR is significantly associated
      with ovarian cancer (P=0.0086). This work identifies a potential new ovarian
      cancer locus and further confirms that cancer resequencing efforts should not
      ignore the study of noncoding regions of cancer patients.

PMID- 24909165
TI  - Nuclear translocation of IGF-1R via p150(Glued) and an importin-beta/RanBP2
      dependent pathway in cancer cells.
AB  - Mounting evidence has shown that the insulin-like growth factor-1 receptor (IGF
      1R) has critical roles in cancer cell growth. This has prompted pharmacological
      companies to develop agents targeting the receptor. Surprisingly, clinical trials
      using specific IGF-1R antibodies have, however, revealed disappointing results.
      Further understanding of the role of IGF-1R in cancer cells is therefore
      necessary for development of efficient therapeutic strategies. Recently, we
      showed that IGF-1R is sumoylated and translocated into the cell nucleus where it
      activates gene transcription. Several other studies have confirmed our findings
      and it has been reported that nuclear IGF-1R (nIGF-1R) has prognostic and
      predictive impact in cancer. To increase the understanding of IGF-1R in cancer
      cells, we here present the first study that proposes a pathway by which IGF-1R
      translocates into the cell nucleus. We could demonstrate that IGF-1R first
      associates with the dynactin subunit p150(Glued), which transports the receptor
      to the nuclear pore complex, where it co-localizes with importin-beta followed by
      association with RanBP2. Sumoylation of IGF-1R seems to be required for
      interaction with RanBP2, which in turn may serve as the SUMO E3 ligase. In the
      context of sumoylation, we provided evidence that it may favor nIGF-1R
      accumulation by increasing the stability of the receptor. Taken together,
      topographic and functional interactions between dynactin, importin-beta and
      RanBP2 are involved in nuclear translocation of IGF-1R. Our results provide new
      understanding of IGF-1R in cancer, which in turn may contribute to development of
      new therapeutic strategies. 

PMID- 24909164
TI  - SIRT3 regulates cellular iron metabolism and cancer growth by repressing iron
      regulatory protein 1.
AB  - Iron metabolism is essential for many cellular processes, including oxygen
      transport, respiration and DNA synthesis, and many cancer cells exhibit
      dysregulation in iron metabolism. Maintenance of cellular iron homeostasis is
      regulated by iron regulatory proteins (IRPs), which control the expression of
      iron-related genes by binding iron-responsive elements (IREs) of target mRNAs.
      Here, we report that mitochondrial SIRT3 regulates cellular iron metabolism by
      modulating IRP1 activity. SIRT3 loss increases reactive oxygen species
      production, leading to elevated IRP1 binding to IREs. As a consequence, IRP1
      target genes, such as the transferrin receptor (TfR1), a membrane-associated
      glycoprotein critical for iron uptake and cell proliferation, are controlled by
      SIRT3. Importantly, SIRT3 deficiency results in a defect in cellular iron
      homeostasis. SIRT3 null cells contain high levels of iron and lose iron-dependent
      TfR1 regulation. Moreover, SIRT3 null mice exhibit higher levels of iron and TfR1
      expression in the pancreas. We found that the regulation of iron uptake and TfR1
      expression contribute to the tumor-suppressive activity of SIRT3. Indeed, SIRT3
      expression is negatively correlated with TfR1 expression in human pancreatic
      cancers. SIRT3 overexpression decreases TfR1 expression by inhibiting IRP1 and
      represses proliferation in pancreatic cancer cells. Our data uncover a novel role
      of SIRT3 in cellular iron metabolism through IRP1 regulation and suggest that
      SIRT3 functions as a tumor suppressor, in part, by modulating cellular iron
      metabolism.

PMID- 24909166
TI  - Smoking accelerates pancreatic cancer progression by promoting differentiation of
      MDSCs and inducing HB-EGF expression in macrophages.
AB  - Smoking is an established risk factor for pancreatic cancer (PC), but late
      diagnosis limits the evaluation of its mechanistic role in the progression of PC.
      We used a well-established genetically engineered mouse model (LSL-K-ras(G12D))
      of PC to elucidate the role of smoking during initiation and development of
      pancreatic intraepithelial neoplasia (PanIN). The 10-week-old floxed mice (K
      ras(G12D); Pdx-1cre) and their control unfloxed (LSL-K-ras(G12D)) littermates
      were exposed to cigarette smoke (total suspended particles: 150 mg/m(3)) for 20
      weeks. Smoke exposure significantly accelerated the development of PanIN lesions
      in the floxed mice, which correlated with tenfold increase in the expression of
      cytokeratin19. The systemic accumulation of myeloid-derived suppressor cells
      (MDSCs) decreased significantly in floxed mice compared with unfloxed controls
      (P<0.01) after the smoke exposure with the concurrent increase in the macrophage
      (P<0.05) and dendritic cell (DCs) (P<0.01) population. Further, smoking-induced
      inflammation (IFN-gamma, CXCL2; P<0.05) was accompanied by enhanced activation of
      pancreatic stellate cells and elevated levels of serum retinoic acid-binding
      protein 4, indicating increased bioavailability of retinoic acid which
      contributes to differentiation of MDSCs to tumor-associated macrophages (TAMs)
      and DCs. TAMs predominantly contribute to the increased expression of heparin
      binding epidermal growth factor-like growth factor (EGFR ligand) in pre
      neoplastic lesions in smoke-exposed floxed mice that facilitate acinar-to-ductal
      metaplasia (ADM). Further, smoke exposure also resulted in partial suppression of
      the immune system early during PC progression. Overall, the present study
      provides a novel mechanism of smoking-induced increase in ADM in the presence of
      constitutively active K-ras mutation.

PMID- 24909167
TI  - TRAIL-R2-specific antibodies and recombinant TRAIL can synergise to kill cancer
      cells.
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces
      apoptosis in cancer cells while sparing normal tissues. Despite promising
      preclinical results, few patients responded to treatment with recombinant TRAIL
      (Apo2L/Dulanermin) or TRAIL-R2-specific antibodies, such as conatumumab (AMG655).
      It is unknown whether this was due to intrinsic TRAIL resistance within primary
      human cancers or insufficient agonistic activity of the TRAIL-receptor (TRAIL-R)
      targeting drugs. Fcgamma receptors (FcgammaR)-mediated crosslinking increases the
      cancer-cell-killing activity of TRAIL-R2-specific antibodies in vivo. We tested
      this phenomenon using FcgammaR-expressing immune cells from patients with ovarian
      cancer. However, even in the presence of high numbers of FcgammaR-expressing
      immune cells, as found in ovarian cancer ascites, AMG655-induced apoptosis was
      not enabled to any significant degree, indicating that this concept may not
      translate into clinical use. On the basis of these results, we next set out to
      determine whether AMG655 possibly interferes with apoptosis induction by
      endogenous TRAIL, which could be expressed by immune cells. To do so, we tested
      how AMG655 affected apoptosis induction by recombinant TRAIL. This, however,
      resulted in the surprising discovery of a striking synergy between AMG655 and non
      tagged TRAIL (Apo2L/TRAIL) in killing cancer cells. This combination was as
      effective in killing cancer cells as highly active recombinant isoleucine-zipper
      tagged TRAIL (iz-TRAIL). The increased killing efficiency was due to enhanced
      formation of the TRAIL death-inducing signalling complex, enabled by concomitant
      binding of Apo2L/TRAIL and AMG655 to TRAIL-R2. The synergy of AMG655 with
      Apo2L/TRAIL extended to primary ovarian cancer cells and was further enhanced by
      combination with the proteasome inhibitor bortezomib or a second mitochondrial
      derived activator of caspases (SMAC) mimetic. Importantly, primary human
      hepatocytes were not killed by the AMG655-Apo2L/TRAIL combination, also not when
      further combined with bortezomib or a SMAC mimetic. We therefore propose that
      clinical-grade non-tagged recombinant forms of TRAIL, such as dulanermin, could
      be combined with antibodies such as AMG655 to introduce a highly active TRAIL-R2
      agonistic therapy into the cancer clinic.

PMID- 24909169
TI  - Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma
      cells.
AB  - CYLD is a deubiquitinating (DUB) enzyme that has a pivotal role in modulating
      nuclear factor kappa B (NF-kappaB) signaling pathways by removing the lysine 63-
      and linear-linked ubiquitin chain from substrates such as tumor necrosis factor
      receptor-associated factor 2 (TRAF2) and TRAF6. Loss of CYLD activity is
      associated with tumorigenicity, and levels of CYLD are lost or downregulated in
      different types of human tumors. In the present study, we found that high CYLD
      expression was associated with better overall survival and relapse-free
      neuroblastoma patient outcome, as well as inversely correlated with the stage of
      neuroblastoma. Retinoic acid-mediated differentiation of neuroblastoma restored
      CYLD expression and promoted SUMOylation of CYLD. This posttranslational
      modification inhibited deubiquitinase activity of CYLD against TRAF2 and TRAF6
      and facilitated NF-kappaB signaling. Overexpression of non-SUMOylatable mutant
      CYLD in neuroblastoma cells reduced retinoic acid-induced NF-kappaB activation
      and differentiation of cells, but instead promoted cell death.

PMID- 24909171
TI  - Ribonucleotide reductase and cancer: biological mechanisms and targeted
      therapies.
AB  - Accurate DNA replication and repair is essential for proper development, growth
      and tumor-free survival in all multicellular organisms. A key requirement for the
      maintenance of genomic integrity is the availability of adequate and balanced
      pools of deoxyribonucleoside triphosphates (dNTPs), the building blocks of DNA.
      Notably, dNTP pool alterations lead to genomic instability and have been linked
      to multiple human diseases, including mitochondrial disorders, susceptibility to
      viral infection and cancer. In this review, we discuss how a key regulator of
      dNTP biosynthesis in mammals, the enzyme ribonucleotide reductase (RNR), impacts
      cancer susceptibility and serves as a target for anti-cancer therapies. Because
      RNR-regulated dNTP production can influence DNA replication fidelity while also
      supporting genome-protecting DNA repair, RNR has complex and stage-specific roles
      in carcinogenesis. Nevertheless, cancer cells are dependent on RNR for de novo
      dNTP biosynthesis. Therefore, elevated RNR expression is a characteristic of many
      cancers, and an array of mechanistically distinct RNR inhibitors serve as
      effective agents for cancer treatment. The dNTP metabolism machinery, including
      RNR, has been exploited for therapeutic benefit for decades and remains an
      important target for cancer drug development.

PMID- 24909170
TI  - Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR
      inhibition in FGFR3-dependent cancer cells.
AB  - Somatic alterations of fibroblast growth factor receptors (FGFRs) have been
      described in a wide range of malignancies. A number of anti-FGFR therapies are
      currently under investigation in clinical trials for subjects with FGFR gene
      amplifications, mutations and translocations. Here, we develop cell line models
      of acquired resistance to FGFR inhibition by exposure of cell lines harboring
      FGFR3 gene amplification and translocation to the selective FGFR inhibitor BGJ398
      and multitargeted FGFR inhibitor ponatinib. We show that the acquisition of
      resistance is rapid, reversible and characterized by an epithelial to mesenchymal
      transition and a switch from dependency on FGFR3 to ERBB family members. Acquired
      resistance was associated with demonstrable changes in gene expression including
      increased production of ERBB2/3 ligands, which were sufficient to drive
      resistance in the setting of FGFR3 dependency but not dependency on other FGFR
      family members. These data support the concept that activation of ERBB family
      members is sufficient to bypass dependency on FGFR3 and suggest that concurrent
      inhibition of these two pathways may be desirable when targeting FGFR3-dependent
      cancers. 

PMID- 24909168
TI  - Phosphorylation of eIF4E promotes EMT and metastasis via translational control of
      SNAIL and MMP-3.
AB  - The progression of cancers from primary tumors to invasive and metastatic stages
      accounts for the overwhelming majority of cancer deaths. Understanding the
      molecular events which promote metastasis is thus critical in the clinic.
      Translational control is emerging as an important factor in tumorigenesis. The
      messenger RNA (mRNA) cap-binding protein eIF4E is an oncoprotein that has an
      important role in cancer initiation and progression. eIF4E must be phosphorylated
      to promote tumor development. However, the role of eIF4E phosphorylation in
      metastasis is not known. Here, we show that mice in which eukaryotic translation
      initiation factor 4E (eIF4E) cannot be phosphorylated are resistant to lung
      metastases in a mammary tumor model, and that cells isolated from these mice
      exhibit impaired invasion. We also demonstrate that transforming growth factor
      beta (TGFbeta) induces eIF4E phosphorylation to promote the translation of Snail
      and Mmp-3 mRNAs, and the induction of epithelial-to-mesenchymal transition (EMT).
      Furthermore, we describe a new model wherein EMT induced by TGFbeta requires
      translational activation via the non-canonical TGFbeta signaling branch acting
      through eIF4E phosphorylation. 

PMID- 24909173
TI  - IL-6 secreted by cancer-associated fibroblasts induces tamoxifen resistance in
      luminal breast cancer.
AB  - Cancer-associated fibroblasts (CAFs) have been implicated in the development of
      resistance to anticancer drugs; however, the role and mechanism underlying CAFs
      in luminal breast cancer (BrCA) tamoxifen resistance are unclear. We found that
      stromal fibroblasts isolated from the central or peripheral area of BrCA have
      similar CAF phenotype and activity. In vitro and in vivo experiments showed that
      CAFs derived from clinical-luminal BrCAs induce tamoxifen resistance through
      decreasing estrogen receptor-alpha (ER-alpha) level when cultured with luminal
      BrCA cell lines MCF7 and T47D. CAFs promoted tamoxifen resistance through
      interleukin-6 (IL-6) secretion, which activates Janus kinase/signal transducers
      and activators of transcription (JAK/STAT3) and phosphatidylinositol 3-kinase
      (PI3K)/AKT pathways in tumor cells, followed by induction of epithelial
      mesenchymal transition and upregulation of E3 ubiquitin ligase anaphase-promoting
      complex 10 activity, which targeted ER-alpha degradation through the ubiquitin
      proteasome pathway. Inhibition of proteasome activity, IL-6 activity or either
      the JAK/STAT3 or PI3K/AKT pathways markedly reduced CAF-induced tamoxifen
      resistance. In xenograft experiments of CAFs mixed with MCF7 cells, CAF-specific
      IL-6 knockdown inhibited tumorigenesis and restored tamoxifen sensitivity. These
      findings indicate that CAFs mediate tamoxifen resistance through IL-6-induced
      degradation of ER-alpha in luminal BrCAs.Oncogene advance online publication, 9
      June 2014; doi:10.1038/onc.2014.158. 

PMID- 24909172
TI  - Mammary glands exhibit molecular laterality and undergo left-right asymmetric
      ductal epithelial growth in MMTV-cNeu mice.
AB  - Significant left-right (L-R) differences in tumor incidence and disease outcome
      occur for cancers of paired organs, including the breasts; however, the basis for
      this laterality is unknown. Here, we show that despite their morphologic
      symmetry, left versus right mammary glands in wild-type mice have baseline
      differences in gene expression that are L-R independently regulated during
      pubertal development, including genes that regulate luminal progenitor cell
      renewal, luminal cell differentiation, mammary tumorigenesis, tamoxifen
      sensitivity and chemotherapeutic resistance. In MMTV-cNeu(Tg/Tg) mice, which
      model HER2/Neu-amplified breast cancer, baseline L-R differences in mammary gene
      expression are amplified, sustained or inverted in a gene-specific manner and the
      mammary ductal epithelium undergoes L-R asymmetric growth and patterning.
      Comparative genomic analysis of mouse L-R mammary gene expression profiles with
      gene expression profiles of human breast tumors revealed significant linkage
      between right-sided gene expression and decreased breast cancer patient survival.
      Collectively, these findings are the first to demonstrate that mammary glands are
      lateralized organs, and, moreover, that mammary glands have L-R differential
      susceptibility to HER2/Neu oncogene-mediated effects on ductal epithelial growth
      and differentiation. We propose that intrinsic molecular laterality may have a
      role in L-R asymmetric breast tumor incidence and, furthermore, that interplay
      between the L-R molecular landscape and oncogene activity may contribute to the
      differential disease progression and patient outcome that are associated with
      tumor situs.

PMID- 24909174
TI  - CXCL12-gamma in primary tumors drives breast cancer metastasis.
AB  - Compelling evidence shows that chemokine C-X-C motif chemokine ligand 12 (CXCL12)
      drives metastasis in multiple malignancies. Similar to other key cytokines in
      cancer, CXCL12 exists as several isoforms with distinct biophysical properties
      that may alter signaling and functional outputs. However, effects of CXCL12
      isoforms in cancer remain unknown. CXCL12-alpha, -beta and -gamma showed cell
      type-specific differences in activating signaling through G protein-dependent
      pathways in cell-based assays, while CXCL12-gamma had greatest effects on
      recruitment of the adapter protein beta-arrestin 2. CXCL12-beta and -gamma also
      stimulated endothelial tube formation to a greater extent than CXCL12-alpha. To
      investigate the effects of CXCL12 isoforms on tumor growth and metastasis, we
      used a mouse xenograft model of metastatic human breast cancer combining CXCR4+
      breast cancer cells and mammary fibroblasts secreting an isoform of CXCL12.
      Altough all CXCL12 isoforms produced comparable growth of mammary tumors, CXCL12
      gamma significantly increased metastasis to bone marrow and other sites. Breast
      cancer cells originating from tumors with CXCL12-gamma fibroblasts upregulated
      RANKL (receptor activator of nuclear factor-kappaB ligand), contributing to bone
      marrow tropism of metastatic cancer cells. CXCL12-gamma was expressed in
      metastatic tissues in mice, and we also detected CXCL12-gamma in malignant
      pleural effusions from patients with breast cancer. In our mouse model, mammary
      fibroblasts disseminated to sites of breast cancer metastases, providing another
      mechanism to increase levels of CXCL12 in metastatic environments. These studies
      identify CXCL12-gamma as a potent pro-metastatic molecule with important
      implications for cancer biology and effective therapeutic targeting of CXCL12
      pathways.

PMID- 24909176
TI  - c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes
      in non-small cell lung cancer by targeting FHIT.
AB  - The dual role of the microRNA-29 (miR-29) family in tumor progression and
      metastasis in solid tumors has been reported. Evidence for the role of miR-29 in
      tumor malignancy and its prognostic value in overall survival (OS) and relapse
      free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting.
      Mechanistic studies presented herein demonstrated that c-Myc suppressed the
      expression of miR-29b, promoting soft agar growth and invasion capability in lung
      cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc
      is responsible for soft agar growth and invasiveness mediated by FHIT loss due to
      promoter methylation. Among patients, low expression of miR-29b and FHIT was more
      common in tumors with high c-Myc expression than in tumors with low c-Myc
      expression. Kaplan-Meier and Cox regression analysis showed that tumors with high
      c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than
      their counterparts. In conclusion, the decrease in the expression of miR-29b by c
      Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor
      outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b
      expression using the c-Myc inhibitor might be helpful in suppressing tumor
      aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC
      patients with tumors with low expression of FHIT.

PMID- 24909175
TI  - A novel function of HER2/Neu in the activation of G2/M checkpoint in response to
      gamma-irradiation.
AB  - In response to gamma-irradiation (IR)-induced DNA damage, activation of cell
      cycle checkpoints results in cell cycle arrest, allowing time for DNA repair
      before cell cycle re-entry. Human cells contain G1 and G2 cell cycle checkpoints.
      While G1 checkpoint is defective in most cancer cells, commonly due to mutations
      and/or alterations in the key regulators of G1 checkpoint (for example, p53,
      cyclin D), G2 checkpoint is rarely impaired in cancer cells, which is important
      for cancer cell survival. G2 checkpoint activation involves activation of ataxia
      telangiectasia-mutated (ATM)/ATM- and rad3-related (ATR) signalings, which leads
      to the inhibition of Cdc2 kinase and subsequent G2/M cell cycle arrest. Previous
      studies from our laboratory show that G2 checkpoint activation following IR
      exposure of MCF-7 breast cancer cells is dependent on the activation of
      extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signaling. As HER
      receptor tyrosine kinases (RTKs), which have important roles in cell
      proliferation and survival, have been shown to activate ERK1/2 signaling in
      response to various stimuli, we investigated the role of HER RTKs in IR-induced
      G2/M checkpoint response in breast cancer cells. Results of the present studies
      indicate that IR exposure resulted in a striking increase in the phosphorylation
      of HER1, HER2, HER3 and HER4 in MCF-7 cells, indicative of activation of these
      proteins. Furthermore, specific inhibition of HER2 using an inhibitor, short
      hairpin RNA and dominant-negative mutant HER2 abolished IR-induced activation of
      ATM/ATR signaling, phosphorylation of Cdc2-Y15 and subsequent induction of G2/M
      arrest. Moreover, the inhibition of HER2 also abrogated IR-induced ERK1/2
      phosphorylation. In contrast, inhibition of HER1 using specific inhibitors or
      decreasing expression of HER3 or HER4 using short hairpin RNAs did not block the
      induction of G2/M arrest following IR. These results suggest an important role of
      HER2 in the activation of G2/M checkpoint response following IR. 

PMID- 24909177
TI  - Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of
      TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin
      loop sequences.
AB  - Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells
      that can remain dormant as epithelial cysts or progress to high-grade sarcoma.
      Predisposing germline loss-of-function DICER1 variants have been described. We
      sought to uncover additional contributors through whole exome sequencing of 15
      tumor/normal pairs, followed by targeted resequencing, miRNA analysis and
      immunohistochemical analysis of additional tumors. In addition to frequent
      biallelic loss  of TP53 and mutations of NRAS or BRAF in some cases, each case
      had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases)
      loss-of-function variant plus a somatic missense mutation in the RNase IIIb
      domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA
      loop sequences normally removed by DICER1. This work both defines a genetic
      interaction landscape with DICER1 mutation and provides evidence for alteration
      in miRNA transcripts as a consequence of DICER1 disruption in cancer. 

PMID- 24909180
TI  - Partially uncovered Cheatham platinum-covered stent to treat complex aortic
      coarctation associated with aortic wall aneurysm.
AB  - Percutaneous treatment of aortic coarctation is a widely used option. Covered
      stents have increased the profile of efficacy and safety of this procedure. Here
      we report on a 32-year-old woman with significant aortic recoarctation associated
      with aortic wall aneurysm and close proximity of both lesions to the origin of
      both the subclavian arteries. It was decided to manually and partially uncover
      the proximal part of the stent to have a hybrid stent that could act as a bare
      stent at the level of the origin of the subclavian arteries and as a covered
      stent at the level of the aneurysm. 

PMID- 24909178
TI  - KSR1 regulates BRCA1 degradation and inhibits breast cancer growth.
AB  - Kinase suppressor of Ras-1 (KSR1) facilitates signal transduction in Ras
      dependent cancers, including pancreatic and lung carcinomas but its role in
      breast cancer has not been well studied. Here, we demonstrate for the first time
      it functions as a tumor suppressor in breast cancer in contrast to data in other
      tumors. Breast cancer patients (n>1000) with high KSR1 showed better disease-free
      and overall survival, results also supported by Oncomine analyses, microarray
      data (n=2878) and genomic data from paired tumor and cell-free DNA samples
      revealing loss of heterozygosity. KSR1 expression is associated with high breast
      cancer 1, early onset (BRCA1), high BRCA1-associated ring domain 1 (BARD1) and
      checkpoint kinase 1 (Chk1) levels. Phospho-profiling of major components of the
      canonical Ras-RAF-mitogen-activated protein kinases pathway showed no significant
      changes after KSR1 overexpression or silencing. Moreover, KSR1 stably transfected
      cells formed fewer and smaller size colonies compared to the parental ones, while
      in vivo mouse model also demonstrated that the growth of xenograft tumors
      overexpressing KSR1 was inhibited. The tumor suppressive action of KSR1 is BRCA1
      dependent shown by 3D-matrigel and soft agar assays. KSR1 stabilizes BRCA1
      protein levels by reducing BRCA1 ubiquitination through increasing BARD1
      abundance. These data link these proteins in a continuum with clinical relevance
      and position KSR1 in the major oncoprotein pathways in breast tumorigenesis.

PMID- 24909181
TI  - A speckle tracking application of ultrasound to evaluate activity of multilayered
      cervical muscles.
AB  - OBJECTIVE: To evaluate the capacity of the ultrasound-based method of speckle
      tracking analysis to detect changes in multilayered dorsal neck muscle activity
      induced by performing a lifting task. SUBJECTS: Twenty-one healthy individuals.
      DESIGN: Participants performed a loaded lifting task in 3 different postural
      orientations of the neck (neutral, flexed and forward head posture). Ultrasound
      images were recorded and speckle tracking analysis was used to quantify muscle
      deformation and deformation rate over 3 equal time-periods during the lifting
      sequence (rest, mid-lift and end-lift). RESULTS: Significant main effects of
      postural orientation for the deformation measure (p < 0.05) and time for the
      deformation rate measure (p < 0.05) were observed in all dorsal muscles examined.
      Significant time by postural interactions for the deformation measure were
      observed in the trapezius, semispinalis cervicis and multifidus (p < 0.05) and in
      the semispinalis cervicis (p < 0.05) for the deformation rate measure.
      CONCLUSION: Speckle tracking analysis ultrasound measurements can detect
      differences in multilayered muscle activity of the dorsal neck induced by
      postural variations during a lifting task. Findings for the deformation and the
      deformation rate measures suggest that they quantify a different, albeit related,
      mechanical event during muscle contraction in a functional task such as lifting.

PMID- 24909179
TI  - PRKACA mediates resistance to HER2-targeted therapy in breast cancer cells and
      restores anti-apoptotic signaling.
AB  - Targeting HER2 with antibodies or small molecule inhibitors in HER2-positive
      breast cancer leads to improved survival, but resistance is a common clinical
      problem. To uncover novel mechanisms of resistance to anti-HER2 therapy in breast
      cancer, we performed a kinase open reading frame screen to identify genes that
      rescue HER2-amplified breast cancer cells from HER2 inhibition or suppression. In
      addition to multiple members of the MAPK (mitogen-activated protein kinase) and
      PI3K (phosphoinositide 3-kinase) signaling pathways, we discovered that
      expression of the survival kinases PRKACA and PIM1 rescued cells from anti-HER2
      therapy. Furthermore, we observed elevated PRKACA expression in trastuzumab
      resistant breast cancer samples, indicating that this pathway is activated in
      breast cancers that are clinically resistant to trastuzumab-containing therapy.
      We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after
      lapatinib or trastuzumab treatment, but rather inactivated the pro-apoptotic
      protein BAD, the BCl-2-associated death promoter, thereby permitting survival
      signaling through BCL-XL. Pharmacological blockade of BCL-XL/BCL-2 partially
      abrogated the rescue effects conferred by PRKACA and PIM1, and sensitized cells
      to lapatinib treatment. These observations suggest that combined targeting of
      HER2 and the BCL-XL/BCL-2 anti-apoptotic pathway may increase responses to anti
      HER2 therapy in breast cancer and decrease the emergence of resistant disease.

PMID- 24909183
TI  - Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant
      prognostic factors in invasive ductal carcinoma of the breast.
AB  - Matrix metalloproteinases (MMPs) are matrix-degrading enzymes that play a pivotal
      role in aggressive behaviours, such as rapid tumour growth, invasion, and
      metastasis, of several types of solid tumours. In particular, stromal MMP-2 plays
      important roles in the progression of malignant tumours, but most clinical
      studies have focused on tumoural MMP-2 and -9 expression, and not stromal MMP-2
      expression. One hundred and seventy-seven cases diagnosed as invasive ductal
      carcinoma of the breast between 2000 and 2005 were included in this study.
      Expressions of tumoural MMP-2 and -9 and stromal MMP-2 were analysed by
      immunostaining on a tissue microarray. Subsequently, the associations between
      those results and various clinicopathological parameters were evaluated. Stromal
      MMP-2 expression correlated significantly with clinicopathological parameters
      such as advanced T category, larger tumour size, high histological grade, tumour
      necrosis, ER- and PR-negative, and HER-2-positive (all p < 0.05). In univariate
      and multivariate analyses, overall survival was linked with stromal MMP-2
      expression as well as dual expression of stromal MMP-2 and tumoural MMP-2 and -9
      (all p < 0.05). Stromal MMP-2 expression may play a crucial role in predicting
      aggressive clinical behaviour in breast cancer patients.

PMID- 24909182
TI  - HLA-G 14-bp polymorphism: a possible marker of systemic treatment response in
      psoriasis vulgaris? Preliminary results of a retrospective study.
AB  - Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule that
      exerts an immunosuppressive function. A 14-base pair (bp) sequence
      insertion/deletion (INS/DEL) polymorphism in the exon 8 at the 3' untranslated
      region (UTR) modifies mRNA stability and protein production and has been shown to
      concur with efficacy of pharmacological treatments in immune-mediated conditions.
      The aim of this study was to assess for the first time the correlation between
      HLA-G 14-bp INS/DEL polymorphism with the response to systemic therapy in
      psoriatic patients. We retrospectively analyzed the HLA-G 14-bp INS/DEL
      polymorphism of HLA-G gene in patients with moderate to severe plaque psoriasis:
      21 treated with acitretin, 16 with cyclosporine, 11 with anti-TNF-alpha. Patients
      who reached PASI 75 at weeks 10-16 were considered responders. Among patients
      treated with acitretin, we observed a significantly increased frequency of the
      HLA-G DEL allele and of the DEL/DEL genotype in responder patients when compared
      with nonresponders. An association between HLA-G genotype and response to
      cyclosporine and biologics was not found. The significant association between HLA
      G 14-bp DEL allele and 14-bp DEL/DEL genotype and acitretin clinical outcome may
      suggest an advantage of this allele and propose this HLA-G polymorphism as a
      potential marker of response to acitretin in psoriatic patients.

PMID- 24909184
TI  - Long-term outcome, complications and disease progression in 23 dogs after
      placement of tracheal ring prostheses for treatment of extrathoracic tracheal
      collapse.
AB  - OBJECTIVE: To report complications, long-term outcome, and disease progression in
      dogs with extrathoracic tracheal collapse treated by surgical placement of
      commercially available extraluminal rings. STUDY DESIGN: Retrospective case
      series. ANIMALS: Dogs (n = 23). METHODS: Medical records (2002-2011) of dogs
      treated with extraluminal rings for extrathoracic tracheal collapse were
      reviewed. Owner interviews, conducted at >10 months postoperatively, determined
      response to surgery, progression of clinical signs after surgery, and frequency
      of medication administration. Long-term re-evaluation (>10 months after surgery)
      was offered for surviving dogs, including radiographs and tracheoscopy if
      indicated. RESULTS: Of 23 dogs, 22 survived to discharge after surgery. Clinical
      signs improved in all dogs at 2 weeks after surgery and at long-term re
      evaluation. Fourteen dogs (65%) required no medical management for respiratory
      signs after surgery. Four dogs (17%) were diagnosed with laryngeal paralysis at
      some point after surgery, but only 9% were diagnosed within 48 hours of the
      surgery. Additional rings were placed between previously placed rings in 2 dogs,
      and 1 dog was treated with an endoluminal stent for intrathoracic tracheal
      collapse. Three dogs had clinical signs consistent with progression of tracheal
      collapse. Based on owner questionnaire, all owners were satisfied with surgical
      outcome. CONCLUSIONS: Treatment of severe cervical tracheal collapse with
      commercially-available extraluminal ring placement leads to an overall
      improvement in quality of life and good long-term results, with about one-third
      of dogs requiring continued medical management. Most dogs do not have clinical
      signs consistent with disease progression after surgery.

PMID- 24909185
TI  - Long-term allogeneic islet graft survival in prevascularized subcutaneous sites
      without immunosuppressive treatment.
AB  - Establishment of noninvasive and efficient islet transplantation site together
      with the avoidance of immunosuppressive drugs for islet engraftment is currently
      the two major tasks for islet transplantation approach to treat patients with
      type 1 diabetes. Here, we proposed a method to achieve long-term allogeneic islet
      graft function without immunosuppression after transplantation in subcutaneous
      sites. Two agarose rods with basic fibroblast growth factor and heparin were
      implanted for 1 week in dorsal subcutaneous sites in diabetic rats. After rod
      removal, 1500 islets were transplanted into the prevascularized pockets. Islets
      transplanted in prevascularized but not nontreated subcutaneous sites rapidly
      reverted hyperglycemia in all streptozotocin-induced diabetic rats. In contrast
      to transient normalization of blood glucose when allogeneic islets were
      transplanted into liver, allogeneic islets transplanted into this prevascularized
      subcutaneous site demonstrated long-term graft survival and function in all three
      rat strain combinations (Fisher 344 to ACI, Lewis to ACI and Fisher 344 to
      Wistar), evidenced by nonfasting blood glucose level, plasma insulin
      concentration, intraperitoneal glucose tolerance test and immunohistochemistry.
      These results indicated that a subcutaneous site prevascularized by this method
      is potentially a suitable site for successful allogeneic islet transplantation
      without immunosuppression. 

PMID- 24909186
TI  - Systemic sarcoidosis with bone marrow involvement showing Propionibacterium acnes
      in the lymph nodes.

PMID- 24909187
TI  - Severe group A streptococcal infections in a paediatric intensive care unit.
AB  - AIM: To describe the clinical presentation, management and outcomes for children
      with invasive group A streptococcal (GAS) infection in a paediatric intensive
      care unit (PICU). METHODS: We reviewed the clinical and laboratory records of
      patients admitted to a PICU in Melbourne with invasive GAS infection from April
      2010 to April 2013. Outcomes recorded included survival, organ failure, need for
      extracorporeal support, renal replacement therapy and prolonged neuromuscular
      weakness. RESULTS: Twelve cases of invasive GAS infection were identified. The
      most common clinical presentations were pneumonia (n=5), bacteraemia with no
      septic focus (n=4) and septic arthritis (n=3). Necrotising fasciitis occurred in
      one patient and another patient presented with ischaemic lower limbs requiring
      amputation. Of the eight isolates with available emm typing results, the most
      common emm type was emm1 (n=4) followed by emm4, 12 and 22. Nine patients had
      multi-organ failure. Ten patients required mechanical ventilation for a median
      duration of 8 days. Nine patients required inotropic and/or vasopressor support
      and four patients extracorporeal membrane oxygenation support. Eleven patients
      survived. A prolonged period of neuromuscular weakness following the initial
      severe illness was common (n=5), but most children returned to normal or near
      normal neurological function. CONCLUSIONS: Invasive GAS disease in children may
      cause severe multi-organ failure with resultant prolonged intensive care stay and
      significant morbidity. However, a high rate of survival and return to normal
      functioning may be achieved with multi-system intensive care support and multi
      disciplinary rehabilitation.

PMID- 24909189
TI  - Quantitative trait loci mapping for conjugated linoleic acid, vaccenic acid and
      ?(9) -desaturase in Italian Brown Swiss dairy cattle using selective DNA pooling.
AB  - A selective DNA pooling approach was applied to identify QTL for conjugated
      linoleic acid (CLA), vaccenic acid (VA) and Delta(9) -desaturase (D9D) milk
      content in Italian Brown Swiss dairy cattle. Milk samples from 60 animals with
      higher values (after correction for environmental factors) and 60 animals with
      lower values for each of these traits from each of five half-sib families were
      pooled separately. The pools were genotyped using the Illumina BovineSNP50
      BeadChip. Sire allele frequencies were compared between high and low tails at the
      sire and marker level for SNPs for which the sires were heterozygous. An r
      procedure was implemented to perform data analysis in a selective DNA pooling
      design. A correction for multiple tests was applied using the proportion of false
      positives among all test results. BTA 19 showed the largest number of markers in
      association with CLA. Associations between SNPs and the VA and Delta(9) 
      desaturase traits were found on several chromosomes. A bioinformatics survey
      identified genes with an important role in pathways for milk fat and fatty acids
      metabolism within 1 Mb of SNP markers associated with fatty acids contents.

PMID- 24909190
TI  - Prevention and management of biliary anastomotic stricture in right-lobe living
      donor liver transplantation.
AB  - Biliary strictures can be categorized according to technical factor as
      anastomotic or nonanastomotic strictures. Biliary anastomotic stricture is a
      common complication after living-donor liver transplantation, occasionally
      causing deaths. The two most commonly used methods for biliary anastomosis are
      duct-to-duct anastomosis and hepaticojejunostomy. Before presenting a description
      of the latest techniques of duct-to-duct anastomosis and hepaticojejunostomy,
      this review first relates the technique of donor right hepatectomy, as most
      biliary complications suffered by recipients of living-donor liver
      transplantation originate from donor operations. Three possible causes of biliary
      anastomotic stricture, namely impaired blood supply, biliary anomaly, and
      technical flaw, are then discussed. Lastly, the review focuses on the latest
      management of biliary anastomotic stricture. Treatment modalities include
      endoscopic retrograde cholangiography with dilatation, percutaneous transhepatic
      biliary drainage with dilatation, conversion of duct-to-duct anastomosis to
      hepaticojejunostomy, and revision hepaticojejunostomy. End-to-side versus side-to
      side hepaticojejunostomy is also discussed. 

PMID- 24909188
TI  - Efficacy and safety of topical glycopyrrolate in patients with facial
      hyperhidrosis: a randomized, multicentre, double-blinded, placebo-controlled,
      split-face study.
AB  - BACKGROUND: Although facial hyperhidrosis has been frequently associated with a
      diminished quality of life, various conservative modalities for its management
      are still far from satisfactory. OBJECTIVE: To evaluate the antiperspirant
      efficacy and safety of the topical glycopyrrolate on facial hyperhidrosis at
      specified posttreatment intervals. METHODS: Thirty-nine patients with facial
      hyperhidrosis were enrolled and treated with 2% topical glycopyrrolate on one
      half of the forehead, whereas the other half of the forehead was treated with a
      placebo. All patients applied topical glycopyrrolate or placebo once a day for
      nine successive days. Each evaluation included weighing sweat and assessing the
      Hyperhidrosis Disease Severity Scale (HDSS) score and any adverse effects.
      RESULTS: Compared with the placebo-treated sides, topical glycopyrrolate-treated
      sides showed a reduction in the rate of sweat production at the forehead of 25.16
      +/- 10.30% (mean +/- SD) at 90 min after the first application (day 1), 29.63 +/-
      7.74% at 24 h after the first application (day 2) and 36.68 +/- 11.41% at 24 h
      after eight additional successive daily applications (day 10) (all P < 0.025).
      There was a little more decrease in HDSS score with the topical glycopyrrolate
      treated half of the forehead, but the difference was not statistically
      significant (P > 0.025). No serious adverse events were reported during the
      course of this study. Only one patient developed a transient headache after
      treatment. CONCLUSION: Topical glycopyrrolate application appears to be
      significantly effective and safe in reducing excessive facial perspiration.

PMID- 24909192
TI  - Clinical efficacy of low-level laser therapy on localized canine atopic
      dermatitis severity score and localized pruritic visual analog score in pedal
      pruritus due to canine atopic dermatitis.
AB  - BACKGROUND: Canine atopic dermatitis is a genetically predisposed inflammatory
      skin disease often requiring multimodal treatment. There is a need to find
      further low-risk adjunctive therapies. HYPOTHESIS/OBJECTIVES: To evaluate the
      localized effect of low-level laser therapy (LLLT) on the paws of dogs with
      atopic dermatitis using a localized canine atopic dermatitis severity score
      (LCADSS) and owner localized pruritic visual analog score (LPVAS) in comparison
      to treatment with a placebo. ANIMALS: Thirty client-owned dogs with symmetrical
      pedal pruritus due to canine atopic dermatitis. METHODS: Dogs were randomly
      assigned into two groups. In each group, one paw was treated with LLLT and one
      paw treated with a placebo laser (comparing either both fore- or hindpaws).
      Treatments were administered at 4 J/cm(2) (area from carpus/tarsus to distal
      aspect of digit 3) three times per week for the first 2 weeks and two times per
      week for the second 2 weeks. Scores were assessed for each paw at weeks 0, 2, 4
      and 5. RESULTS: There were no significant differences in LCADSS or LPVAS between
      LLLT and placebo treatments between weeks 0 and 5 (P = 0.0856 and 0.5017,
      respectively). However, LCADSS and LPVAS significantly decreased from week 0 at
      weeks 2, 4 and 5 in both LLLT and placebo groups (P < 0.0001 for all).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Low-level laser therapy is not an effective
      localized treatment for pedal pruritus in canine atopic dermatitis.

PMID- 24909191
TI  - Uterine-sparing minimally invasive interventions in women with uterine fibroids:
      a systematic review and indirect treatment comparison meta-analysis.
AB  - OBJECTIVE: To evaluate the effectiveness of uterine-sparing interventions for
      women with symptomatic uterine fibroids who wish to preserve their uterus.
      DESIGN: Systematic review and indirect comparison meta-analysis. METHODS:
      MEDLINE, EMBASE, CENTRAL, conference proceedings, trial registers and reference
      lists were searched up to October 2013 for randomized controlled trials. MAIN
      OUTCOME MEASURES: Outcome measures were patient satisfaction, re-intervention and
      complications rates, reproductive outcomes, and hospitalization and recovery
      times. RESULTS: Five trials, involving 436 women were included; two compared
      uterine artery embolization with myomectomy and three compared uterine artery
      embolization with laparoscopic uterine artery occlusion. Indirect treatment
      comparison showed that myomectomy and uterine artery embolization resulted in
      higher rates of patient satisfaction (odds ratio 2.56, 95% credible interval 0.56
      11.75 and 2.7, 95% credible interval 1.1-7.14, respectively) and lower rates of
      clinical failure (odds ratio 0.29, 95% credible interval 0.06-1.46 and 0.37, 95%
      credible interval 0.13-0.93, respectively) than laparoscopic uterine artery
      occlusion. Myomectomy resulted in lower re-intervention rate than uterine artery
      embolization (odds ratio 0.08, 95% credible interval 0.02-0.27) and laparoscopic
      uterine artery occlusion (odds ratio 0.08, 95% credible interval 0.01-0.37) even
      though the latter techniques had an advantage over myomectomy because of shorter
      hospitalization and quicker recovery. There was no evidence of difference between
      the three techniques in ovarian failure and complications rates. The evidence for
      reproductive outcomes is poor. CONCLUSION: Our study's results suggest that
      laparoscopic uterine artery occlusion is less effective than uterine artery
      embolization and myomectomy in treatment of symptomatic fibroids. The choice
      between uterine artery embolization and myomectomy should be based on
      individuals' expectations and fully informed discussion.

PMID- 24909193
TI  - Outcome of patients with severe PH due to lung disease with and without targeted
      therapy.
AB  - INTRODUCTION: Pulmonary hypertension (PH) can occur in patients with lung disease
      and worsen prognosis. Endothelin receptor antagonists, phosphodiesterase 5
      inhibitors, and prostacyclin analogs, referred to as targeted therapy, have not
      been shown in a limited number of controlled clinical studies to improve exercise
      capacity in these patients. Possibly targeted therapy could be of benefit in
      patients with severe PH due to lung disease, but this subgroup is not well
      studied. AIMS: To analyze influence of PH severity and use of targeted therapy on
      exercise capacity and survival in patients with PH due to lung disease. METHODS:
      Consecutive patients with PH (mean pulmonary artery pressure >=25 mmHg at rest)
      due to lung disease diagnosed by right heart catheterization between 1/2005 and
      9/2011 were retrospectively included. Severe PH was defined as mean pulmonary
      artery pressure >=35 mmHg. Patients were followed until 4/2012 for exercise
      capacity, survival, and targeted therapy use. RESULTS: Patients with severe PH (n
      = 40) received significantly more often targeted therapy compared to the 32
      patients with less severe PH (65% vs. 25%, P = 0.001). Survival was not
      significantly different between these groups (P = 0.310). Patients on targeted
      therapy were older, more often female, and had worse hemodynamic impairment, but
      significantly higher estimated 1-, 3-, and 5-year survival rates compared to
      untreated patients (97%, 81%, and 75% vs. 83%, 54%, and 19%, respectively; P =
      0.002). This effect was mainly driven by the patients with severe PH, in whom the
      survival advantage was statistically significant on subgroup analysis (HR 0.182,
      P = 0.002). Exercise capacity was not significantly altered in any patient group.
      CONCLUSION: Patients with severe PH due to lung disease may have a survival
      benefit from targeted therapy compared to untreated patients with less severe PH.
      Prospective clinical trials utilizing targeted therapy and long-term endpoints
      are justified in this patient group.

PMID- 24909194
TI  - Hypothermia and atrial fibrillation.

PMID- 24909195
TI  - A new paradigm for primary prevention strategy in people with elevated risk of
      stroke.
AB  - Existing methods of primary stroke prevention are not sufficiently effective.
      Based on the recently developed Stroke Riskometer app, a new 'mass-elevated risk
      stroke/cardiovascular disease prevention' approach as an addition to the
      currently adopted absolute risk stroke/cardiovascular disease prevention approach
      is being advocated. We believe this approach is far more appealing to the
      individuals concerned and could be as efficient as the conventional population
      based approach because it allows identification and engagement in prevention of
      all individuals who are at an increased (even slightly increased) risk of stroke
      and cardiovascular disease. The key novelty of this approach is twofold. First,
      it utilizes modern far-reaching mobile technologies, allowing individuals to
      calculate their absolute risk of stroke within the next 5 to 10 years and to
      compare their risk with those of the same age and gender without risk factors.
      Second, it employs self-management strategies to engage the person concerned in
      stroke/cardiovascular disease prevention, which is tailored to the person's
      individual risk profile. Preventative strategies similar to the Stroke Riskometer
      could be developed for other non-communicable disorders for which reliable
      predictive models and preventative recommendations exist. This would help reduce
      the burden of non-communicable disorders worldwide. 

PMID- 24909196
TI  - Sleep-related symptoms in Ecuadorian natives/mestizos with and without stroke: an
      Atahualpa Project case-control nested study.

PMID- 24909197
TI  - Update protocol Preventive Antibiotics in Stroke Study (PASS).

PMID- 24909198
TI  - The INTERnational Study on Primary Angiitis of the CEntral nervous system--a call
      to the world.

PMID- 24909199
TI  - Internal borderzone infarction is associated with hemodynamic compromise in
      patients with carotid occlusion but not with recurrent stroke.

PMID- 24909200
TI  - GFAP variants in health and disease: stars of the brain... and gut.

PMID- 24909201
TI  - The Effect of Platelet Proteins Released in Response to Titanium Implant Surfaces
      on Macrophage Pro-Inflammatory Cytokine Gene Expression.
AB  - BACKGROUND AND PURPOSE: Platelets are one of the earliest cell types to interact
      with surgically inserted titanium implants. This in vitro study investigated the
      effect of titanium surface-induced platelet releasate on macrophage cytokine gene
      expression. MATERIALS AND METHODS: To mimic the in vivo temporal sequence of
      platelet arrival and protein production at the implant surface and the subsequent
      effect of these proteins on mediators of the immune response, the levels of
      platelet attachment and activation in response to culture on smooth polished,
      sandblasted and acid-etched (SLA), and hydrophilic-modified SLA (modSLA) titanium
      surfaces were first determined by microscopy and protein assay. The subsequent
      effect of the platelet-released proteins on human THP-1 macrophage cytokine gene
      expression was determined by polymerase chain reaction array after 1 and 3 days
      of macrophage culture on the titanium surfaces in platelet-releasate conditioned
      media. RESULTS: Platelet attachment was surface dependent with decreased
      attachment observed on the hydrophilic (modSLA) surface. The platelet releasate,
      when considered independently of the surface effect, elicited an overall pro
      inflammatory response in macrophage cytokine gene expression, that is, the
      expression of typical pro-inflammatory cytokine genes such as TNF, IL1a, IL1b,
      and CCL1 was significantly up-regulated whereas the expression of anti
      inflammatory cytokine genes such as IL10, CxCL12, and CxCL13 was significantly
      down-regulated. However, following platelet exposure to different surface
      modifications, the platelet releasate significantly attenuated the macrophage pro
      inflammatory response to microrough (SLA) titanium and hastened an anti
      inflammatory response to hydrophilic (modSLA) titanium. CONCLUSIONS: Theses
      results demonstrate that titanium surface topography and chemistry are able to
      influence the proteomic profile released by platelets, which can subsequently
      influence macrophage pro-inflammatory cytokine expression. This immunomodulation
      may be an important mechanism via which titanium surface modification influences
      osseointegration.

PMID- 24909204
TI  - Subacute cutaneous lupus erythematosus induced by the new multikinase inhibitor
      pazopanib.

PMID- 24909202
TI  - Inhibitory action of naphtho[1,2-b]furan-4,5-dione on hepatocyte growth factor
      induced migration and invasion of MDA-MB-231 cells: mechanisms of action.
AB  - Naphtho[1,2-b]furan-4,5-dione (NFD), a bioactive component of Avicennia marina,
      has been shown to exhibit anticancer activity. The aim of the present study was
      to explore the effect of NFD on hepatocyte growth factor (HGF)-induced cell
      migration and invasion of MDA-MB-231 human breast cancer cells, as well as the
      underlying mechanism of action. Cell viability was determined using the 3-(4,5
      dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay, western blot
      analysis was used to measure protein expression and cell migration and invasion
      were evaluated by the cell wound healing assay, Boyden chamber assay and gelatin
      zymography. When cells were treated with non-toxic concentrations of NFD (1-3
      MUmol/L, 24 h), NFD concentration-dependently inhibited HGF-promoted cell
      migration and invasion. Simultaneously, NFD efficiently suppressed c-Met
      phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K)
      and Akt. In addition, NFD inhibited the phosphorylation of IkappaB kinases and
      IkappaBalpha and nuclear translocation of nuclear factor (NF)-kappaB, as well as
      matrix metalloproteinase (MMP)-9 activity. Furthermore, the c-Met inhibitor
      PHA665752 (10 MUmol/L) inhibited HGF-induced MMP-9 expression, cell migration and
      invasion, as well as the activation of PI3K/Akt, suggesting that PI3K/Akt
      activation occur downstream of c-Met activation. In conclusion, the results of
      the present study suggest that NFD inhibits HGF-induced invasion and migration of
      MDA-MB-231 cells via HGF- and/or c-Met-mediated PI3K/Akt and NF-kappaB signalling
      pathways, leading to downregulation of MMP-9 expression and cell migration. 

PMID- 24909203
TI  - Effect of Camellia sinensis supplementation and increasing holding time on
      quality of cryopreserved boar semen.
AB  - Cryopreservation of boar semen is still considered suboptimal due to the low
      fertility when compared with fresh semen. This study was performed to evaluate
      the effects of green tea (Camellia sinensis) supplementation of the freezing
      extender at different concentration (0, 2.5%, 5%, 10%) and also to determine the
      influence of increasing holding time from 2 to 24 h at 15  degrees C. Seventeen
      ejaculates from nine boars were used to make pools of three of them and then
      cryopreserved. Sperm motility, viability, acrosome integrity, membrane
      functionality (HOST) and capacitation status were determined before freezing and
      at 0, 30, 60, 90 and 120 min after thawing. Lipid peroxidation was evaluated just
      after thawing. The main findings emerging from this study were the following: (i)
      no improvement in quality of thawed spermatozoa with addition of tea to the
      freezing extender, (ii) no improvement in quality of thawed spermatozoa with
      prolonged holding time, (iii) lower peroxidation rate in presence of tea 5% and
      (iv) a decrease in the number of uncapacited viable spermatozoa with any tea
      supplementation. We conclude that amplification of holding time in semen
      cryopreservation process does not vary results, facilitating freezing protocol.
      Tea supplementation reduces lipoxidation but did not improve quality parameters. 

PMID- 24909205
TI  - Estimating the impact of unsafe water, sanitation and hygiene on the global
      burden of disease: evolving and alternative methods.
AB  - The 2010 global burden of disease (GBD) study represents the latest effort to
      estimate the global burden of disease and injuries and the associated risk
      factors. Like previous GBD studies, this latest iteration reflects a continuing
      evolution in methods, scope and evidence base. Since the first GBD Study in 1990,
      the burden of diarrhoeal disease and the burden attributable to inadequate water
      and sanitation have fallen dramatically. While this is consistent with trends in
      communicable disease and child mortality, the change in attributable risk is also
      due to new interpretations of the epidemiological evidence from studies of
      interventions to improve water quality. To provide context for a series of
      companion papers proposing alternative assumptions and methods concerning the
      disease burden and risks from inadequate water, sanitation and hygiene, we
      summarise evolving methods over previous GBD studies. We also describe an
      alternative approach using population intervention modelling. We conclude by
      emphasising the important role of GBD studies and the need to ensure that policy
      on interventions such as water and sanitation be grounded on methods that are
      transparent, peer-reviewed and widely accepted. 

PMID- 24909206
TI  - Safety of closed-loop therapy during reduction or omission of meal boluses in
      adolescents with type 1 diabetes: a randomized clinical trial.
AB  - We evaluated the safety and efficacy of closed-loop therapy with meal
      announcement during reduction and omission of meal insulin boluses in adolescents
      with type 1 diabetes (T1D). Twelve adolescents with T1D [six male; mean (s.d.)
      age 15.9 (1.8) years; mean (s.d.) glycated haemoglobin (HbA1c) 77 (27) mmol/mol]
      were studied in a randomized crossover study comparing closed-loop therapy with
      meal announcement with conventional pump therapy over two 24-h stays at a
      clinical research facility. Identical meals were given on both occasions. The
      evening meal insulin bolus was calculated to cover half of the carbohydrate
      content of the meal and no bolus was delivered for lunch. Plasma glucose levels
      were in the target range of 3.9-10 mmol/l for a median [interquartile range
      (IQR)] of 74 (55,86)% of the time during closed-loop therapy with meal
      announcement and for 62 (49,75)% of the time during conventional therapy (p =
      0.26). Median (IQR) time spent with plasma glucose levels > 10 mmol/l [23 (13,39)
      vs. 27 (10,50)%; p = 0.88] or < 3.9 mmol/l [1(0,4) vs. 5 (1,10)%; p = 0.24] and
      mean [standard deviation (SD)] glucose levels [8.0 (7.6,9.3) vs. 7.7 (6.6,10.1)
      mmol/l, p = 0.79] were also similar. In conclusion, these results assist home
      testing of closed-loop delivery with meal announcement in adolescents with poorly
      controlled T1D who miscalculate or miss meal insulin boluses.

PMID- 24909208
TI  - Rapid spread of emerging Zika virus in the Pacific area.

PMID- 24909207
TI  - Vasorelaxant effects of novel Kv 7.4 channel enhancers ML213 and NS15370.
AB  - BACKGROUND AND PURPOSE: The KCNQ-encoded voltage-gated potassium channel family
      (Kv 7.1-Kv 7.5) are established regulators of smooth muscle contractility, where
      Kv 7.4 and Kv 7.5 predominate. Various Kv 7.2-7.5 channel enhancers have been
      developed that have been shown to cause a vasorelaxation in both rodent and human
      blood vessels. Recently, two novel Kv 7 channel enhancers have been identified,
      ML213 and NS15370, that show increased potency, particularly on Kv 7.4 channels.
      The aim of this study was to characterize the effects of these novel enhancers in
      different rat blood vessels and compare them with Kv 7 enhancers (S-1, BMS204352,
      retigabine) described previously. We also sought to determine the binding sites
      of the new Kv 7 enhancers. KEY RESULTS: Both ML213 and NS15370 relaxed segments
      of rat thoracic aorta, renal artery and mesenteric artery in a concentration
      dependent manner. In the mesenteric artery ML213 and NS15370 displayed EC50 s
      that were far lower than other Kv 7 enhancers tested. Current-clamp experiments
      revealed that both novel enhancers, at low concentrations, caused significant
      hyperpolarization in mesenteric artery smooth muscle cells. In addition, we
      determined that the stimulatory effect of these enhancers relied on a tryptophan
      residue located in the S5 domain, which is the same binding site for the other Kv
      7 enhancers tested in this study. CONCLUSIONS AND IMPLICATIONS: This study has
      identified and characterized ML213 and NS15370 as potent vasorelaxants in
      different blood vessels, thereby highlighting these new compounds as potential
      therapeutics for various smooth muscle disorders.

PMID- 24909209
TI  - Reactivity profile of a peri-substitution-stabilized phosphanylidene-phosphorane:
      synthetic, structural, and computational studies.
AB  - The reactions of peri-substitution-stabilized phosphanylidene-phosphorane 1 with
      [AuCl(tht)] or [PtCl2(cod)] afford binuclear complexes [((1)(AuCl)2)2] 2 and
      [((1)(PtCl2))2] 3, in which four electrons of the ligand are used in bonding to
      two metal atoms in the bridging arrangement. Reactions of 1 with [Mo(CO)4(nbd)]
      or (RhCl2Cp*)2 afford mononuclear complexes [(1)2Mo(CO)4] 4 and [(1)RhCl2Cp*] 5,
      in which two electrons of the ligand are used to form terminal complexes.
      Formation of these complexes disrupts the negative hyperconjugation at the P-P
      bond to various extents, which is mirrored by variations in their P-P bond
      distances (2.179(4)-2.246(4) A). The P-P bond is ruptured upon formation of Pd
      diphosphene complex 6, which is likely to proceed through a phosphinidene
      intermediate. In air, 1 is fully oxidized to phosphonic acid 7. Reactions of 1
      with chalcogens under mild conditions generally afford mixtures of products, from
      which the trithionated 8, dithionated 9, diselenated 10, and monotellurated 11
      species were isolated. The bonding in the chalcogeno derivatives is discussed
      using DFT (B3LYP) and natural bond orbital analysis, which indicate a
      contribution from dative bonding in 8-10. The buttressing effect of the peri
      backbone is shown to be an essential factor in the formation of the single push
      double-pull bis(borane) 13. This is demonstrated experimentally through a
      synthesis parallel to that used to make 13, but lacking the backbone, which leads
      to different products. The P-P bond distances in the reported products, as well
      as additional species, are correlated with Wiberg bond indices, showing very good
      agreement for a variety of bonding modes, including the negative
      hyperconjugation. 

PMID- 24909210
TI  - Japanese guidelines for the management of pemphigus.
AB  - The Committee for Guidelines for the Management of Pemphigus was organized as one
      element of the Japanese Dermatological Association (JDA) and the Ministry of
      Health, Labour, and Welfare (MHLW) Research Project on Measures for Research
      Committee for Intractable Skin Disease. Pemphigus has been defined as a group of
      intractable autoimmune blistering diseases caused by anti-desmoglein 1 and/or
      anti-desmoglein 3 IgG autoantibodies by the MHLW. The diagnosis of this condition
      and the criteria for assessing its severity are based on suggestions from the
      MHLW Research Group. The clinical practice guidelines presented here are those
      that are currently recommended in Japan. However, symptoms and complications can
      vary widely among individual pemphigus patients, so not all therapies will be
      required to be in complete agreement with these guidelines. 

PMID- 24909211
TI  - Measurement of cutaneous lymphatic flow rates in patients with skin cancer: area
      extraction method.
AB  - Some recent reports have revealed that the long scintigraphic appearance time
      (SAT), defined as the time between radionuclide injection and first sentinel
      lymph node (SLN) visualization in lymphoscintigraphy, is a negative predictive
      parameter of nodal metastasis in patients with melanoma. However, most of the
      methods used to measure the SAT were ambiguous because they utilized
      visualization in lymphoscintigraphy. We herein introduce a novel method by which
      to measure the SAT and lymphatic flow rate. The data of 33 patients with primary
      skin cancer were used. Sequential images were obtained using dynamic
      lymphoscintigraphy, and a time-activity curve of the SLN was created. The time at
      which the counts reached plateau was newly defined as an alternative to the SAT
      and was termed the scintigraphic saturation time (SST). The figure obtained by
      division of the distance by the SST was newly defined as an alternative to the
      lymphatic flow rate and termed the lymphatic transit rate (LTR). The SST was
      clearly determined. It ranged from 220 to 1430 s (mean, 805 s). Pathological
      examination revealed nodal metastasis in five patients. In 28 patients without
      metastasis, the mean LTR was in the order of lower limbs (4.07 +/- 0.35 cm/min),
      upper limbs (2.67 +/- 0.33 cm/min), trunk (1.79 +/- 0.47 cm/min), and head and
      neck (1.11 +/- 0.22 cm/min). The LTRs were higher in patients with nodal
      metastasis than those without. This method may be effective for accurate
      measurement of the SAT and lymphatic flow rate.

PMID- 24909212
TI  - Study of the usefulness of patch testing and use test to predict the safety of
      commercial topical drugs.
AB  - Patch testing (PT) can be used to identify allergens and irritants responsible
      for contact allergic and irritant dermatitis, respectively. However, the
      reproducibility of PT and correlation between PT and use test has not been fully
      evaluated. The aim of the present study was to examine the reproducibility of PT
      and its usefulness in assessing the safety of topical drugs. A total of 55
      topical drugs were applied to the backs of two groups of subjects for either 24
      or 48 h, and skin irritant reactions were graded at 2 and 24 h after patch
      removal. For the repeat open application test, six topical drugs with different
      irritation scores were applied to the arms of two groups of subjects twice daily
      for 3 weeks, and local symptoms were recorded. The mean irritation scores were
      similar between the two PT groups. The percentage of subjects positive for
      symptoms provoked by the use tests was similar between the two groups. The mean
      irritation scores 24 h after patch removal correlated with the skin symptoms
      provoked by the use test. PT was reproducible and the results correlated with the
      use test results. PT is a useful method for evaluating the safety of commercial
      topical drugs.

PMID- 24909214
TI  - Evaluation of sentinel node biopsy for cutaneous squamous cell carcinoma.
AB  - Sentinel lymph node biopsy (SLNB) is a standard care for cutaneous melanoma but
      its role in cutaneous squamous cell carcinoma (SCC) has not been established.
      Clinical data was obtained from 54 patients with SCC who received SLNB with the
      usage of blue dye and radioisotope colloid methods. The positive rate of SLNB in
      SCC was 7.4%. If the cases were limited to more than T2, the positive rate was
      12.9%. Three of 41 patients who was estimated negative LN metastasis by the
      preoperative tests had micrometastasis (7.3%). Among 13 patients who were
      suggested to have metastasis in the preoperative tests, only one patient had
      histological metastasis. One patient with SCC located in the lower lip showed
      negative SLNB and subsequently developed node recurrence. In conclusion, the
      efficacy of SLNB in SCC is comparable to that of melanoma in the positive rate.
      There are two kinds of benefit, avoidance of unnecessary complete lymph node
      dissection and early detection of metastasis. 

PMID- 24909213
TI  - A novel TRPS1 mutation in a family with tricho-rhino-phalangeal syndrome type 1.
AB  - Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal-dominant disease
      characterized by sparse and slow-growing scalp hair and craniofacial and skeletal
      abnormalities. We report here the case of two girls and their father who had TRPS
      type 1 and received a diagnosis of a new mutation of TRPS1 based on their
      clinical symptoms. Moreover, histological studies on skin samples obtained from
      one of the patients showed enhanced signal transducers and activator of
      transcription (STAT) 3 expression in the outer root sheath. However, TRPS1
      protein expression was not reduced in the patient's follicles. These findings
      indicate that truncated TRPS1 protein from the mutant allele may be stably
      expressed in the patient's follicles and that enhanced STAT3 expression may be
      involved in the development of sparse and thin scalp hair in TRPS. 

PMID- 24909215
TI  - Successful differentiation of herpes zoster-associated erythema multiforme from
      generalized extension of herpes by rapid polymerase chain reaction analysis.
AB  - The polymerase chain reaction (PCR) assay for varicella zoster virus (VZV),
      herpes simplex virus (HSV)-1 and HSV-2 is available for use. Sometimes the
      differential diagnosis of the generalized herpes zoster (HZ), HSV1/2, and drug
      eruption is difficult. We report a case of HZ followed by the vesicular erythema
      multiforme (EM)-like lesion. In this case the use of PCR was of great assistance.
      A 78-year-old Japanese man without any significant previous history of disease
      was admitted to our hospital complaining of zosteriform vesicle on an
      erythematous base from his right shoulder to the upper arm. We diagnosed him with
      HZ at the level of right Th2. In spite of the prompt start of antiviral therapy,
      a secondary new vesiculous erythema developed on his trunk. Clinically, it was
      quite difficult to differentiate the lesion from the generalized HZ. Rapid PCR
      assay of effusion and crust for VZV was performed. A PCR assay of VZV was
      positive for the crust taken from the primary lesion, while it was negative for
      the effusion and crust of the secondary widespread lesion. We diagnosed the
      secondary widespread lesion as an EM-type drug eruption induced by acyclovir, or
      an EM associated with herpes zoster. We then stopped the use of acyclovir and
      applied steroid ointment of a very strong class for the secondary lesions, which
      improved after a few days. A PCR assay for VZV was useful for ruling out the
      generalized HZ in our case with secondary developed vesiculous lesions. 

PMID- 24909217
TI  - Identification of the cause of severe skin infection by Fournier transform
      infrared spectroscopy: a case of Fournier's gangrene caused by fish bone.
AB  - Fournier's gangrene (FG) is an infrequent but highly lethal infection. Here we
      report a 74-year-old man who presented with genital swelling and severe malaise.
      Based on the physical and imaging examination results, the diagnosis of FG was
      confirmed. Intraoperative findings showed dirty necrosis of soft tissue, and a
      splinter-shaped foreign body was found in the perirectal region. The foreign body
      was thought to be the cause of the condition, and it was analyzed using Fourier
      transform infrared spectroscopy. We found that the foreign body was a mixture of
      calcium phosphate and protein, suggesting that the splinter was a bone. Moreover,
      during the medical interview, the patient mentioned about intake of fish around
      the time of onset of symptoms. Therefore, to confirm the results of the analysis,
      DNA was extracted from the foreign body, and genomic PCR with subsequent sequence
      analysis was performed. The DNA sequence was identical to that of Oncorhynchus
      kisutch, a salmon that is a very popular food in Japan. On the basis of these
      findings, we concluded that FG in this case was caused by the penetration into
      the rectum of an accidentally ingested fish bone. Although some cases of intra
      abdominal abscess due to accidental ingestion of fish bone have been reported, FG
      caused by fish bone is extremely rare. 

PMID- 24909216
TI  - Bowenoid papulosis successfully treated with imiquimod 5% cream.
AB  - A 24-year-old healthy Japanese female was diagnosed as having bowenoid papulosis
      in the genital area. The histopathological findings revealed acanthosis,
      papillomatosis, dyskeratotic cells and clumping cells with mild atypical nuclei.
      Human papillomavirus type 16 was detected in the lesion. The lesion was
      successfully treated with topical imiquimod 5% cream after 2 months. Imiquimod 5%
      cream is a potentially effective treatment modality for lesions that are
      difficult to treat with surgical excision.

PMID- 24909218
TI  - Transverse nasal lesions: a Japanese study.

PMID- 24909219
TI  - A case of anti-BP180 type mucous membrane pemphigoid treated with intravenous
      immunoglobulin.

PMID- 24909220
TI  - A case of ophiasis type of alopecia areata in a patient with ring chromosome 18
      syndrome.

PMID- 24909221
TI  - Severe contact urticarial syndrome due to oxidative hair dye containing para
      aminophenol and sodium-methyl-oleoyl-taurate.

PMID- 24909222
TI  - Multiple pilomatricomas in a patient with Turner syndrome.

PMID- 24909223
TI  - Histopathological evaluation of paradoxical immune reconstitution inflammatory
      syndrome-associated Kaposi's sarcoma.

PMID- 24909224
TI  - A case of Miescher's type of acral melanocytic nevus.

PMID- 24909226
TI  - A broadband plasmonic enhanced transparent conductor.
AB  - We have designed a high performance transparent conductor using silver and
      aluminium stacked films perforated with hexagonally periodic subwavelength holes
      which are close to the lattice period. A broadband (lambda of 400-800 nm)
      enhanced transmission is achieved by strong coupling of surface plasmons and
      propagating modes through the holes. Optical and electrical modeling predict a
      good combination of transparency and sheet resistance (e.g. ~85% T and ~2.4 Omega
      sq(-1)). Preliminary characterization results of the samples made via nanosphere
      lithography will also be presented. 

PMID- 24909225
TI  - RNAi-mediated gene silencing in zebrafish triggered by convergent transcription.
AB  - RNAi based strategies to induce gene silencing are commonly employed in numerous
      model organisms but have not been extensively used in zebrafish. We found that
      introduction of transgenes containing convergent transcription units in zebrafish
      embryos induced stable transcriptional gene silencing (TGS) in cis and trans for
      reporter (mCherry) and endogenous (One-Eyed Pinhead (OEP) and miR-27a/b) genes.
      Convergent transcription enabled detection of both sense and antisense
      transcripts and silencing was suppressed upon Dicer knockdown, indicating
      processing of double stranded RNA. By ChIP analyses, increased silencing was
      accompanied by enrichment of the heterochromatin mark H3K9me3 in the two
      convergently arranged promoters and in the intervening reading frame. Our work
      demonstrates that convergent transcription can induce gene silencing in zebrafish
      providing another tool to create specific temporal and spatial control of gene
      expression. 

PMID- 24909227
TI  - A sensitive method for protein assays using a peptide-based nano-label: human
      glypican-3 detection for hepatocellular carcinomas diagnosis.
AB  - In this work, we propose a sensitive method to detect proteins by using a peptide
      based nano-label. This label is fabricated by attaching the streptavidin-specific
      peptide to a streptavidin-coated gold nanoparticle. In the meantime, the nano
      label is used in combination with a capture probe prepared by using the specific
      peptide of the target protein and biotin. In the detection procedure, the target
      proteins can specifically bind with the biotinylated capture probes which have
      been previously immobilized on an electrode surface, thus the probes can be
      protected from thermolysin cleavage. Consequently, the capture probes can be
      tethered with the nano-labels through the robust biotin-streptavidin interaction,
      resulting in facile electron transfer between the nano-labels and the electrode.
      Taking the detection of human glypican-3 (GPC3), a valuable biomarker for
      hepatocellular carcinoma (HCC), as an example, experimental results demonstrate
      that the proposed method can show excellent performance. Moreover, based on the
      serum level of GPC3 detected by our method, HCC can be efficiently differentiated
      from benign hepatic disorders. Owing to its analytical merits and acceptable
      applications in real samples, the proposed method may hold great potential in
      clinical practice in the future. 

PMID- 24909228
TI  - Intermediate metallic phase in VO2 observed with scanning tunneling spectroscopy.
AB  - This investigation focuses on the formation of nanoscale puddles of an
      intermediate metallic phase (IMP) in the metal-insulator transition (MIT)
      temperature regime of single-crystalline vanadium dioxide (VO2) nanowires. The
      electronic structure of VO2 nanowires was examined with scanning tunneling
      spectroscopy. The evolution of the local density of states of individual
      nanowires throughout the MIT regime is presented with differential tunneling
      conductance spectra and images measured as the temperature was increased. Our
      results show that the formation of an IMP plays an important role in the MIT of
      intrinsic VO2. 

PMID- 24909229
TI  - Flagellin concentrations in expectorations from cystic fibrosis patients.
AB  - BACKGROUND: The aim was to measure flagellin concentrations in the expectorations
      of CF patients and to examine whether there are correlations with the level of
      respiratory insufficiency and inflammation. METHODS: Sputum samples from 31 adult
      patients chronically colonized with P. aeruginosa were collected and analysed for
      their content of flagellin and IL-8. Clinical data were extracted from patient
      files. RESULTS: Regardless of whether patients are colonized with mucoid strains
      or not, they carry clones of P. aeruginosa that express flagellin. While
      flagellin was present in airways of all of our CF patients, it is difficult to
      ascertain its contribution to inflammation (IL-8) and lung function
      deterioration. CONCLUSIONS: This is the first demonstration that flagellin is
      present in the sputum of patients. Thus, attempts to down regulate inflammation
      by the use of TLR5 (flagellin receptor) antagonists remain a possibility.
      However, this result needs to be extended to a larger number of patients to
      validate it for future research on this subject.

PMID- 24909230
TI  - Drugs against Mycobacterium tuberculosis 3-isopropylmalate dehydrogenase can be
      developed using homologous enzymes as surrogate targets.
AB  - 3-Isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tuberculosis (Mtb) may
      be a target for specific drugs against this pathogenic bacterium. We have
      expressed and purified Mtb IPMDH and determined its physicalchemical and
      enzymological properties. Size-exclusion chromatography and dynamic light
      scattering measurements (DLS) suggest a tetrameric structure for Mtb IPMDH, in
      contrast to the dimeric structure of most IPMDHs. The kinetic properties (kcat
      and Km values) of Mtb IPMDH and the pH-dependence of kcat are very similar to
      both Escherichia coli (Ec) and Thermus thermophilus (Tt) IPMDHs. The stability of
      Mtb IPMDH in 8 M urea is close to that of the mesophilic counterpart, Ec IPMDH,
      both of them being much less stable than the thermophilic (Tt) enzyme. Two known
      IPMDH inhibitors, O-methyl oxalohydroxamate and 3-methylmercaptomalate, have been
      synthesised. Their inhibitory effects were found to be independent of the origin
      of IPMDHs. Thus, experiments with either Ec or Tt IPMDH would be equally relevant
      for designing specific inhibitory drugs against Mtb IPMDH.

PMID- 24909231
TI  - A novel fed-batch based strategy for enhancing cell-density and recombinant
      cyprosin B production in bioreactors.
AB  - Nowadays, the dairy industry is continuously looking for new and more efficient
      clotting enzymes to create innovative products. Cyprosin B is a plant aspartic
      protease characterized by clotting activity that was previously cloned in
      Saccharomyces cerevisiae BJ1991 strain. The production of recombinant cyprosin B
      by a batch and fed-batch culture was compared using glucose and galactose as
      carbon sources. The strategy for fed-batch cultivation involved two steps: in the
      first batch phase, the culture medium presented glucose 1 % (w/v) and galactose
      0.5 % (w/v), while in the feed step the culture medium was constituted by 5 %
      (w/v) galactose with the aim to minimize the GAL7 promoter repression. Based on
      fed-batch, in comparison to batch growth, an increase in biomass (6.6-fold),
      protein concentration (59 %) and cyprosin B activity (91 %) was achieved. The
      recombinant cyprosin B was purified by a single hydrophobic chromatography,
      presenting a specific activity of 6 * 10(4) U.mg(-1), corresponding to a
      purification degree of 12.5-fold and a recovery yield of 16.4 %. The SDS-PAGE
      analysis showed that recovery procedure is suitable for achieving the purified
      recombinant cyprosin B. The results show that the recombinant cyprosin B
      production can be improved based on two distinct steps during the fed-batch,
      presenting that this strategy, associated with a simplified purification
      procedure, could be applied to large-scale production, constituting a new and
      efficient alternative for animal and fungal enzymes widely used in cheese making.

PMID- 24909232
TI  - Betulinic acid and its derivatives: a patent review (2008-2013).
AB  - INTRODUCTION: Betulinic acid (BA) is a triterpenoid that can be obtained from
      renewable resources. BA is cytotoxic to many human tumor cell lines mainly by
      apoptosis but cell death might also be triggered by nonapoptotic pathways. Many
      derivatives have been synthesized to improve the very weak solubility of parent
      BA and to increase its cytotoxicity as well as its selectivity toward tumor
      cells. AREAS COVERED: A brief introduction into cancer is given reflecting the
      different pathways this disease might be treated using chemotherapy using natural
      product analogs especially triterpenes. The different ways of action of BA in
      cancer cells are discussed. Finally, this review describes the main synthetic
      modifications that have been performed and discusses, in short, the structure
      activity relationships of these analogs, investigated between 2008 and 2013
      including some important publications from early 2014. EXPERT OPINION: A number
      of patents on BA analogs for the chemotherapy of cancer have been reported
      between 2008 and 2013. Most of these patents deal with modifications at positions
      C-3, C-20 and C-28. There are only a few compounds meeting the needs of a
      sufficient hydrosolubility, while retaining high cytotoxicity and selectivity
      toward tumor cells. Thus, one might expect that there will be some efforts in
      developing molecules of improved solubility and to find new and more efficient
      forms of administration (liposomes, transdermal application and nanoemulsions).
      An important sideline might be the treatment of the age-dependent degeneration of
      the macula, a possible caveat of which might be a certain degree of CNS toxicity
      associated with several derivatives of BA.

PMID- 24909233
TI  - Patterns of reported problems in women and men with back and neck pain:
      similarities and differences.
AB  - OBJECTIVE: To examine similarities and differences in problem areas reported by
      women and men who seek physiotherapy for back or neck pain. METHODS: Principal
      component analysis (PCA) was used to analyse questionnaire data including
      demographics, pain, domestic work, stress, health status, physical disability,
      psychosocial and physical workload, kinesiophobia and self- efficacy. Most of the
      questions were recruited from a number of scales, e.g. EuroQol (EQ-5D), Neck
      Disability Index (NDI), Oswestry Disability Questionnaire (ODQ), Tampa Scale for
      Kinesiophobia, and Functional-Efficacy-Scale. RESULTS: A total of 118 patients
      (84 women, 34 men) completed the questionnaire. Men and women scored similarly on
      physical disability, functional self-efficacy and kinesiophobia, but women scored
      higher on stress reactions and pain intensity. PCA showed that questions about
      physical disability and functional self-efficacy comprised the first component
      and explained most of the variance in this patient group. Questions about stress
      and social support at work constituted the second component. Questions about
      domestic workload and pain comprised the third component. Gender differences were
      found in the second and third components. CONCLUSION: In general, women and men
      answered questions similarly, but there were differences: more women reported
      stress, pain and low support at work and more men reported a lower domestic
      workload.

PMID- 24909234
TI  - Biotransformation and bioactivation reactions of alicyclic amines in drug
      molecules.
AB  - Aliphatic nitrogen heterocycles such as piperazine, piperidine, pyrrolidine,
      morpholine, aziridine, azetidine, and azepane are well known building blocks in
      drug design and important core structures in approved drug therapies. These core
      units have been targets for metabolic attack by P450s and other drug metabolizing
      enzymes such as aldehyde oxidase and monoamine oxidase (MAOs). The electron rich
      nitrogen and/or alpha-carbons are often major sites of metabolism of alicyclic
      amines. The most common biotransformations include N-oxidation, N-conjugation,
      oxidative N-dealkylation, ring oxidation, and ring opening. In some instances,
      the metabolic pathways generate electrophilic reactive intermediates and cause
      bioactivation. However, potential bioactivation related adverse events can be
      attenuated by structural modifications. Hence it is important to understand the
      biotransformation pathways to design stable drug candidates that are devoid of
      metabolic liabilities early in the discovery stage. The current review provides a
      comprehensive summary of biotransformation and bioactivation pathways of
      aliphatic nitrogen containing heterocycles and strategies to mitigate metabolic
      liabilities.

PMID- 24909235
TI  - The artefacts of radiochromic film dosimetry with flatbed scanners and their
      causation by light scattering from radiation-induced polymers.
AB  - Optical experiments and theoretical considerations have been undertaken in order
      to understand the causes of the 'orientation effect' and the 'parabola effect',
      the artefacts impairing the desired light absorption measurement on radiochromic
      EBT3 films with flatbed scanners. EBT3 films exposed to doses up to 20.9 Gy were
      scanned with an Epson Expression 10000XL flatbed scanner in landscape and
      portrait orientation. The horizontally and vertically polarized light components
      of the scanner were determined, and another Epson Expression 10000XL flatbed
      scanner was disassembled to examine its optical components. The optical
      properties of exposed and unexposed EBT3 films were studied with incident
      polarized and unpolarized white light, and the transmitted red light was
      investigated for its polarization and scattering properties including the
      distribution of the scattering angles. Neutral density filters were studied for
      comparison. Guidance was sought from the theory of light scattering from rod-like
      macromolecular structures. The drastic dose-dependent variation of the
      transmitted total light current as function of the orientation of front and rear
      polarizers, interpreted by light scattering theory, shows that the radiation
      induced polymerization of the monomers of EBT3 films produces light scattering
      oscillators preferably polarized at right angles with the coating direction of
      the film. The directional distribution of the scattered light is partly
      anisotropic, with a preferred scattering plane at right angles with the coating
      direction, indicating light scattering from stacks of coherently vibrating
      oscillators piled up along the monomer crystals. The polyester carrier film also
      participates in these effects. The 'orientation' and 'parabola' artefacts due to
      flatbed scanning of radiochromic films can be explained by the interaction of the
      polarization-dependent and anisotropic light scattering from exposed and
      unexposed EBT3 films with the quantitative difference between the scanner's
      horizontally and vertically polarized light supply and with the limited
      directional acceptance of the scanner's light recording system. 

PMID- 24909236
TI  - Incidence and type of meniscal injury and associated long-term clinical outcomes
      in dogs treated surgically for cranial cruciate ligament disease.
AB  - OBJECTIVE: To evaluate factors related to meniscal pathology and their effect on
      clinical outcome in dogs treated for cranial cruciate ligament (CCL) disease.
      STUDY DESIGN: Prospective cross-sectional study. ANIMALS: Dogs (n = 163) with CCL
      disease (n = 223 stifles). METHODS: CCL disease was treated by (1) arthroscopy
      and TightRope (TR) stabilization; (2) arthroscopy and tibial plateau leveling
      osteotomy (TPLO); or (3) open arthrotomy and TPLO. Incidences of concurrent and
      subsequent meniscal tears, meniscal treatments, mid-(6 months) and long-(>1 year)
      term outcomes by owner assessment were compared among surgical treatment groups.
      RESULTS: Concurrent meniscal tears were diagnosed in 83% of stifles assessed by
      arthroscopy and 44% of stifles assessed by arthrotomy, with concurrent tear
      diagnosis being 1.9 times more likely by arthroscopy than arthrotomy (P < .001).
      Incidence of diagnosis of subsequent meniscal tears was 6.7% with median time to
      diagnosis of 5.8 months. Differences in proportion of subsequent meniscal tears
      among treatment groups were not significant (P = .69). Subsequent meniscal tears
      were diagnosed in 21% of cases without concurrent meniscal tears, but only 1.3%
      of cases with concurrent meniscal tears (P < .001). Cases treated with meniscal
      release did not have subsequent meniscal tears, whereas dogs not treated with
      meniscal release had a subsequent meniscal tear rate of 11% (P = .0013). Cases
      diagnosed and treated for concurrent meniscal tears were 1.3 times more likely to
      have a successful long-term outcome (P = .007). CONCLUSIONS: CCL surgical
      technique did not affect subsequent meniscal tear rate or mid-term or long-term
      functional outcomes, whereas diagnosis and treatment of concurrent meniscal tears
      did significantly affect both.

PMID- 24909238
TI  - The great East Japan earthquake disaster: distribution of hospital damage in
      Miyagi Prefecture.
AB  - INTRODUCTION: In catastrophic events, a key to reducing health risks is to
      maintain functioning of local health facilities. However, little research has
      been conducted on what types and levels of care are the most likely to be
      affected by catastrophic events. Problem The Great East Japan Earthquake Disaster
      (GEJED) was one of a few "mega disasters" that have occurred in an industrialized
      society. This research aimed to develop an analytical framework for the holistic
      understanding of hospital damage due to the disaster. METHODS: Hospital damage
      data in Miyagi Prefecture at the time of the GEJED were collected
      retrospectively. Due to the low response rate of questionnaire-based surveillance
      (7.7%), publications of the national and local governments, medical associations,
      other nonprofit organizations, and home web pages of hospitals were used, as well
      as literature and news sources. The data included information on building damage,
      electricity and water supply, and functional status after the earthquake.
      Geographical data for hospitals, coastline, local boundaries, and the in undated
      areas, as well as population size and seismic intensity were collected from
      public databases. Logistic regression was conducted to identify the risk factors
      for hospitals ceasing inpatient and outpatient services. The impact was displayed
      on maps to show the geographical distribution of damage. RESULTS: Data for 143
      out of 147 hospitals in Miyagi Prefecture (97%) were obtained. Building damage
      was significantly associated with closure of both inpatient and outpatient wards.
      Hospitals offering tertiary care were more resistant to damage than those
      offering primary care, while those with a higher proportion of psychiatric care
      beds were more likely to cease functioning, even after controlling for hospital
      size, seismic intensity, and distance from the coastline. CONCLUSIONS:
      Implementation of building regulations is vital for all health care facilities,
      irrespective of function. Additionally, securing electricity and water supplies
      is vital for hospitals at risk for similar events in the future. Improved data
      sharing on hospital viability in a future event is essential for disaster
      preparedness.

PMID- 24909237
TI  - Enhancing human islet transplantation by localized release of trophic factors
      from PLG scaffolds.
AB  - Islet transplantation represents a potential cure for type 1 diabetes, yet the
      clinical approach of intrahepatic delivery is limited by the microenvironment.
      Microporous scaffolds enable extrahepatic transplantation, and the
      microenvironment can be designed to enhance islet engraftment and function. We
      investigated localized trophic factor delivery in a xenogeneic human islet to
      mouse model of islet transplantation. Double emulsion microspheres containing
      exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a
      layered scaffold design consisting of porous outer layers for islet
      transplantation and a center layer for sustained factor release. Protein
      encapsulation and release were dependent on both the polymer concentration and
      the identity of the protein. Proteins retained bioactivity upon release from
      scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing
      scaffolds demonstrated significant improvement and prolongation of graft function
      relative to blank scaffolds carrying no protein, and the release profile
      significantly impacted the duration over which the graft functioned. Ex4
      releasing scaffolds enabled better glycemic control in animals subjected to an
      intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood
      glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4
      delivering scaffolds provide an extrahepatic transplantation site for modulating
      the islet microenvironment to enhance islet function posttransplant. 

PMID- 24909239
TI  - Lycopene and resveratrol improve post-thaw bull sperm parameters: sperm motility,
      mitochondrial activity and DNA integrity.
AB  - We focussed on evaluating the protective effect of lycopene and resveratrol on
      post-thaw bull sperm and oxidative stress parameters. Nine ejaculates for each
      bull were used in the study. Each ejaculate, splitted into three equal aliquots
      and diluted at 37  degrees C with base extenders containing lycopene (1 * 10(-3) 
      g ml(-1) ) and resveratrol (1 mm), and no antioxidant (control), was cooled to 5 
      degrees C and then frozen. Frozen straws were thawed in a water bath for
      evaluation. The supplementation of the semen extender with lycopene and
      resveratrol increased the percentages of post-thawed computer-assisted sperm
      analysis (CASA) motility (55.8 +/- 3.8 and 61.9 +/- 4.0%) and progressive
      motility (38 +/- 2.4 and 37 +/- 8.8), compared with the controls (50.7 +/- 2.65
      and 33.3 +/- 3.74%, respectively, P < 0.05). Resveratrol provided a higher ALH
      (4.3 +/- 0.1), in comparison with the control (3.9 +/- 0.3, P < 0.05). The
      supplementation of the semen extender with lycopene and resveratrol produced a
      higher mitochondrial activity (24.6 +/- 2.9 and 30.1 +/- 6.5% respectively),
      compared with that of the control (11.8 +/- 9.5%, P < 0.05). It was determined
      that both antioxidants resulted in a lower percentage of sperm with damaged DNA
      than that of the control (P < 0.05). Sperm motion characteristics except for ALH,
      acrosome integrity, sperm viability and oxidative stress parameters were not
      affected by the adding of lycopene and resveratrol. 

PMID- 24909240
TI  - Effects of sodium selenite on aflatoxin B1-induced decrease of ileal IgA+ cell
      numbers and immunoglobulin contents in broilers.
AB  - This study was aimed to assess the protective effect of sodium selenite on the
      ileum mucosal immunologic injury induced by AFB1. One hundred eighty-one-day-old
      healthy male Avian broilers were divided into four groups of three replicates and
      15 birds per replicate and fed with basal diet (control group), 0.3 mg/kg AFB1
      (AFB1 group), 0.4 mg/kg Se (+Se group), and 0.3 mg/kg AFB1 + 0.4 mg/kg Se (AFB1 +
      Se group) respectively. The numbers of IgA(+) cells of ileum were determined by
      immunohistochemistry as well as the contents of sIgA, IgA, IgG, and IgM in the
      mucosa of ileum by ELISA. Compared with those in the control group, the numbers
      of IgA(+) cells as well as the sIgA, IgA, IgG, and IgM contents were decreased in
      the AFB1 group. However, compared with those in the AFB1 group, the numbers of
      IgA(+) cells as well as the sIgA, IgA, IgG, and IgM contents were increased in
      the AFB1 + Se group, and these data had no difference between AFB1 + Se group and
      control group. It was concluded that 0.3 mg/kg AFB1 could reduce the humoral
      immune function of the ileum mucosa, but 0.4 mg/kg supplemented dietary selenium
      could protect the mucosal humoral immune function from AFB1-induced impairment.

PMID- 24909242
TI  - The creation of hope in patients with lung cancer.
AB  - BACKGROUND: Lung cancer is associated with biomedical and psychological symptoms
      as well as a generally poor prognosis. When healthcare staff communicate with
      lung cancer patients it is essential that they consider the patients' own views
      of the situation to avoid putting unnecessary strain upon the patients'
      shoulders. The purpose of the present study is to better understand how a group
      of patients with lung cancer reflects upon their new life situation after
      diagnosis and primary treatment. METHOD: Fifteen patients with non-small cell
      lung cancer were consecutively included and, where possible, repeatedly
      interviewed during the course of the disease process. The 29 interviews were
      conducted in a thematically structured narrative form that facilitated a dialog
      between the interviewer and the patient. The interviews covered experiences with
      health care, living an everyday life, and thoughts about the future. FINDINGS AND
      REFLECTIONS: By focusing on how the patients more or less preconsciously
      elaborated mentally with their vulnerable situation, it was possible to detect
      different mental manoeuvres that they used as a way of creating hope. The
      patients distanced themselves from their disease, relied on a feeling of a sound
      body, idealised treatment possibilities, relied on healthy behaviour, focused on
      a concrete project, found that they were better off than others, and took solace
      in the fact that there were patients who had successfully managed the disease.
      DISCUSSION: The patients were not passive victims in the face of their diagnosis,
      but were actively trying to find ways of looking at their despairing situation in
      a positive light. A creative process for psychological survival had thus been
      initiated by the patients. We suggest that acknowledging this process should be
      the starting point from which physicians can engage in hope work with their
      patients.

PMID- 24909241
TI  - Clinical and Histomorphometric Evaluation of Fresh Frozen Bone Allograft in Sinus
      Lift Surgery.
AB  - PURPOSE: The aim of this prospective clinical study was to evaluate the clinical
      and histomorphometric data of newly formed bone tissue from fresh frozen human
      allograft in sinus lift surgery. PATIENTS AND METHODS: Thirty-three sinus lift
      procedures were performed in 20 patients, divided into two groups. The control
      group (n = 8) received autogenous bone from the mandibular ramus, and the
      experimental group (n = 12) received fresh frozen bone (FFB) allograft in chips.
      After 6 months, 52 implants were placed and 50 biopsies were collected for
      histomorphometric analysis. Cone beam computed tomography scans were performed at
      preoperative, immediate postoperative, and delayed postoperative time intervals
      to assess the degree of graft volume loss. RESULTS: There was no statistically
      significant difference between groups as regards degree of graft volume loss (p =
      .983), total bone area (p = .191), remaining particles (p = .348), and proportion
      of active osteoblasts (p = .867). There was a statistically significant
      difference in the vitality rate between the groups (p = .043). In both groups,
      all implants were clinically osseointegrated after 4 months. CONCLUSION: FFB
      allograft was shown to be a feasible substitute for autogenous bone graft in
      sinus lift surgery.

PMID- 24909243
TI  - The placebo-nocebo response in patients with depression: do we need to reconsider
      our treatment approach and clinical trial designs?

PMID- 24909244
TI  - Therapeutic drug monitoring and pharmacogenetics--is this a way towards creative
      psychopharmacotherapy?
AB  - Modern development trends in psychiatry incorporate greater care for patients and
      above all individualisation of therapeutic approaches. Therapeutic drug
      monitoring (TDM) for phenotyping and genotyping of drug metabolism are possible
      determinants of improved treatment efficacy, reduced adverse effects of
      psychotropic drugs, and enhanced treatment compliance. They render possible
      individual adjustment of psychopharmacological treatment and thus represent a
      small, but significant piece in the mosaic of creative psychopharmacotherapy. 

PMID- 24909245
TI  - Placebo and nocebo effect: a mini-review.
AB  - It is well-known that placebo is a substance without medical effects, which
      benefits the health status because of the patient's belief that the substance is
      effective and that the nocebo is defined as a substance without medical effects
      but which worsenes the health status of the person taking it by the negative
      beliefs and expectations of the patient. Starting with the history of the placebo
      effect and giving a review of the most significant studies reporting about the
      placebo effect from 1939-2013 it was our intention to give the all-around look on
      this phenomena discussing the neurobiological and other theories of its origin
      and concentrating especially on the field of psychiatry and finally coming to
      conclusions regarding the conductance of clinical trials and ethics. Regarding
      psychiatry, the placebo effect has a substantial role in most of psychiatric
      conditions including depression, anxiety, addictions, and contrary to what may
      have been expected, schizophrenia. Likewise, the nocebo effect is not to be
      neglected as the studies are being conducted to identify the factors causing it
      so it could be prevented. 

PMID- 24909246
TI  - Suicide in bipolar disorder: a review.
AB  - BACKGROUND: Suicide is a leading cause of death in patients with bipolar
      disorder. Risk factors and prevention of suicide in this illness are the focus of
      considerable current research. METHODS: MEDLINE data base was searched for the
      key words "bipolar disorder" with "suicide", "lithium" with "suicide",
      "anticonvulsants" with "bipolar disorder", and "anticonvulsants" with "bipolar
      disorder" and with "suicide". No language or time constraints were applied. The
      lists of references were searched manually to find additional articles. RESULTS:
      It is estimated that 25% to 50% of patients with bipolar disorder will attempt
      suicide at least once over their lifetime, and that 8% to 19% will complete
      suicide. Mortality rates from cardiovascular diseases are elevated in bipolar
      disorder. Risk factors for suicide include younger age of onset of the illness,
      history of past suicidal behavior, family history of suicide acts, comorbid
      borderline personality disorder and substance use disorders, and hopelessness.
      The warning signs calling for immediate action include the patients threatening
      to harm themselves, or looking for ways to kill themselves (seeking access to
      pills or weapons), or the patient talking or writing about death. Robust evidence
      supports the effects of lithium treatment in reducing suicidal attempts and
      completions in bipolar disorder. The evidence for antisuicidal effects of
      anticonvulsants is weaker. Nevertheless, valproate and other anticonvulsants are
      frequently prescribed as mood stabilizers. There have been controversial
      suggestions that this treatment may elevate the risk of suicide, but the data
      supporting this are not convincing. Psychoeducation can reduce the number of
      suicide attempts and completions. CONCLUSIONS: Suicide in bipolar disorder is a
      major public health problem. Recent research has expanded our knowledge of risk
      factors and warning signs. Nevertheless, it appears that the introduction of
      lithium treatment in the 1970s was the most recent important breakthrough in the
      prevention of suicide in this illness.

PMID- 24909247
TI  - Assessment and treatment of the risk of psychosis in adolescents--a review.
AB  - BACKGROUND: When psychosis first presents, and particularly in the case of
      schizophrenia, the guidelines recommend rapid institution of treatment with
      atypical antipsychotics. Two different clinical pictures can be observed:
      psychoses with acute onset and those with insidious onset. Acute cases (60% of
      the total) have a favourable course in 85% of young patients but where onset is
      insidious and the symptoms are predominantly negative, the course is poor in 25%
      of subjects. Since acute symptoms are relatively easy to diagnose, it is
      diagnosis of the 'insidious/negative' cases that represents a major challenge. Is
      such a diagnosis possible yet? How can we limit the number of false negatives and
      false positives with the attendant risk of stigma? What treatment should be
      administered? METHODS: Review of the literature (PubMed, PsycARTICLES, PsycINFO)
      and comparison with clinical practice here. RESULTS: Young people with a high
      risk of developing psychosis can be identified using scales such as SOPS (Scale
      of Prodromal Symptoms), PACE (Personal Assessment and Crisis Evaluation) or from
      the presence of neuroanatomical and genetic characteristics. Unfortunately, these
      tools are more specific for positive symptoms, and therefore identify a sub
      population of young people at risk: those at Ultra-High Risk (UHR). It can be
      argued that effective treatment is available for these UHR young people to
      prevent the condition from developing into schizophrenia. On the other hand, the
      problem persists for young people presenting an insidious onset and predominantly
      negative symptoms: to date we have no real way of either screening them or
      assessing the efficacy of a treatment. CONCLUSION: "Ultra-High Risk" patients are
      starting to represent a separate nosological entity. This entity is made up of
      young patients, most of whom have positive symptoms. If left untreated, the
      course will lead to seriously compromised social and psychological functioning.
      Rapid diagnosis and treatment for UHRs is therefore essential. In the future we
      need to refine our diagnostic tools to make them sufficiently specific and
      sensitive but also so that the widest category of "Risk Syndrome for Psychosis"
      includes young patients with mostly negative symptoms.

PMID- 24909248
TI  - Social functioning of patients with psychotic disorders in long-term
      psychodynamic group psychotherapy: preliminary research.
AB  - BACKGROUND: In recent years, social functioning of patients has increasingly been
      used as a criterion for assessing therapeutic efficacy of the group
      psychotherapy. The purpose of this preliminary study was to examine whether
      social functioning of patients with diagnosed psychotic disorders changes during
      their participation in psychodynamic group psychotherapy. SUBJECT AND METHODS:
      The sample consisted of 30 patients involved in the psychodynamic group
      psychotherapy (PGP), and a comparative group of 30 patients treated only with
      antipsychotic medication therapy (treatment as usual; TAU). After two years of
      therapy, the instruments designed for this study (self-assessment and therapist
      assessment questionnaire) were applied to examine changes in patient
      communication in their interpersonal relations, romantic and working functioning,
      and overall social functioning. The research also included data as to whom
      patients turned to for help, and the number of hospitalisations in the observed
      period. RESULTS: The majority of patients from both groups assessed their social
      functioning as improved, with significant differences found only in the area of
      romantic relations: more patients in the TAU group assessed their functioning as
      worsened. Nevertheless, a significantly higher number of patients in the PGP
      group were assessed by their therapists to have improved social functioning in
      all dimensions, except in the area of romantic relations, where there was no
      statistically significant difference between the groups. In comparison with the
      TAU group, twice as many patients in the PGP group turned to their psychiatrist
      for help and had four times fewer hospitalisations. CONCLUSION: Considering the
      limitations of this preliminary study, it can be concluded that the findings are
      promising, although further research is required to determine whether a
      psychodynamic approach to group psychotherapy truly leads to improved social
      functioning of patients with psychotic disorders.

PMID- 24909249
TI  - Phemenological aspects of personality disorders in adult psychiatric patients.
AB  - BACKGROUND: Many empirical studies give evidence of co-occurrence of mental and
      personality disorders (PDs). On the other hand theoretical models explain the
      relationship between personality and mental disorders from different
      perspectives. This research studied the phemenological aspects of PDs in adult
      psychiatric patients with different mental disorders according to cognitive and
      psychoanalytic criteria for personality pathology. SUBJECTS AND METHODS: In order
      to study personality pathology in different diagnostic groups we constructed a
      self-report Questionnaire of Personality Disorders (VMO-2) on the basis of the
      DSM-IV-TR classification of PD (APA 2000), Beck's theory of dysfunctional beliefs
      (Beck et al. 2004) and psychoanalytic theories of personality (Kernberg 1986).
      The content of items in VMO-2 reflected the phenomenology of PDs and is focused
      on the basic experience of self and others in specific personality types. The
      questionnaire consists of 193 items which are divided into 11 clinical scales
      (Histrionic, Obsessive-compulsive, Avoidant, Dependent, Depressive, Narcissistic,
      Borderline, Antisocial, Paranoid, Schizoid and Schizotypal PD scale) and a
      validity (Lie) scale. The sample of 642 adult patients with different mental
      disorders and 477 healthy controls of both genders served as subjects in the
      study. RESULTS: All groups of patients reached higher scores on VMO-2 and
      revealed more personality pathology as compared to the control group. There were
      differences in specific personality scales between patients of different
      diagnostic groups. The schizotypal PD scale discriminated significantly between
      patients with schizophrenia and the majority of other diagnostic groups. The
      group of patients with opioid dependence disorder reached the highest mean score
      on the scale for antisocial PD. CONCLUSION: Our results on VMO-2 show partial
      support for psychodynamic and cognitive theories of personality pathology.
      Results are also in accordance with other empirical studies which show that some
      characteristics of PDs relate to specific mental disorders. We discuss
      methodological problems regarding some uncontrolled factors which could influence
      the results of our study. Despite some limitations the present study confirms the
      relationship between the phenomenological aspect of personality pathology and
      mental disorders.

PMID- 24909250
TI  - Personality disorder functioning styles are associated with the effects of the
      cognitive-behavioral therapy for panic disorder: a preliminary study.
AB  - BACKGROUND: The effect of the cognitive behavioral therapy (CBT) for panic
      disorder varies, but how personality disorder functioning style influences it
      remains unclear. SUBJECTS AND METHODS: In 30 healthy volunteers and 44 patients
      with panic disorder (22 treated and 22 waiting list), we administered the Parker
      Personality Measure (PERM) and the Plutchik-van Praag Depression Inventory (PVP).
      Before and during the CBT or waiting period, patients were asked to record their
      panic attacks using the Panic Attack Record (PAR). RESULTS: Patients scored
      significantly higher on PERM Antisocial, Borderline, Histrionic, Avoident,
      Dependent, and Passive-aggressive styles and on depression. After CBT, all PAR
      parameters were significantly reduced in the treated group. The Obsessive
      compulsive style was positively correlated with the panic attack duration and the
      total-thought before CBT or waiting period in all patients. In treated patients,
      the decreased panic attack duration was positively correlated with Histrionic,
      Obsessive-compulsive and Passive-aggressive; the decreased total symptom number
      was positively correlated with Antisocial and Histrionic; the decreased total
      sensation was positively correlated with antisocial; and the total-thought was
      positively correlated with Narcissistic style. CONCLUSIONS: The length and
      duration of CBT was short and mainly with behavioral strategies, how personality
      influenced the related cognition per se remains unknown here. However, our
      preliminary results indicate that personality disorder functioning styles related
      to the externalized behaviors and the Obsessive-compulsive style have positive
      effects on CBT for panic disorder, implying that CBT practitioners should note
      their personality styles when treating these patients.

PMID- 24909251
TI  - Leptin -2548g/a gene polymorphism in association with antipsychotic-induced
      weight gain: a meta-analysis study.
AB  - BACKGROUND: The leptin -2548G/A (rs7799039) gene polymorphism has been implicated
      in susceptibility to antipsychotic-induced weight gain (AIWG), but study results
      are still controversial. The present meta-analysis was performed to investigate
      the relationship between the leptin -2548G/A gene polymorphism and AIWG. METHODS:
      Electronic databases were searched for eligible articles in English and Chinese
      and seven separate studies on the association of the leptin -2548G/A gene
      polymorphism with AIWG were analyzed. RESULTS: The meta-analysis involved 451
      AIWG patients and 568 controls. The pooled odds ratio (OR) and their
      corresponding 95% confidence interval (CI) were calculated by a fixed or random
      effect. Overall, our meta-analysis suggests that the leptin -2548G/A gene
      polymorphism was not significantly associated with AIWG risk under various
      genetic models. But, in the subgroup analysis by ethnicity, significant
      association was found between leptin -2548A allele and the AIWG risk in Asian
      populations under additive, dominant, recessive, and homozygote genetic model. On
      the contrary, in European populations, the -2548A allele seemed to decrease the
      risk of AIWG when compared with the -2548G allele under various genetic models,
      even though they were not statistically significant. CONCLUSION: Our meta
      analysis suggests that the correlation between leptin -2548G/A gene polymorphism
      and AIWG risk has significant racial differences.

PMID- 24909252
TI  - Is suicide mortality associated with meteorological and socio-economic factors?
      An ecological study in a city in Taiwan with a high suicide rate.
AB  - BACKGROUND: Keelung City has the highest suicide rate in Taiwan. This study aimed
      to determine whether meteorological and socio-economic factors are associated
      with suicide mortality in Keelung City, by gender and by means of suicide.
      SUBJECTS AND METHODS: Data on suicides between January 2006 and December 2010
      were provided by the Department of Health, Keelung City Government. The suicide
      victims were categorized into non-violent and violent groups, based on the
      International Classification of Disease, Ninth Revision. Meteorological data were
      obtained from the Central Weather Bureau of Taiwan. Socio-economic data were
      gathered from the Accounting and Statistics Office, Keelung City Government.
      Multiple linear regression analysis with backward elimination was performed to
      determine the model that was most effective in predicting dependent variables.
      RESULTS: During the 5-year study period, the overall suicide mortality rate was
      negatively associated with ambient temperature. Male suicide mortality was
      positively correlated with unemployment, and negatively correlated with ambient
      temperature, barometric pressure, rainy days, family income and number of
      holidays. Female suicide mortality and violent suicide mortality were not
      significantly correlated with any meteorological or socio-economic factors. Non
      violent suicide mortality was positively correlated with unemployment, and
      negatively correlated with ambient temperature, barometric pressure and family
      income. CONCLUSIONS: Suicide is a complex psychopathological phenomenon. Further
      studies with individual data are warranted to confirm how meteorological and
      socio-economic conditions influence ones' suicidal behaviour.

PMID- 24909253
TI  - Nightmares and suicide: predicting risk in depression.
AB  - BACKGROUND: There is growing evidence of an association of a number of subjective
      and objective sleep parameters (especially nightmares) and elevated suicidal risk
      in different clinical populations as well as in the general populations. SUBJECTS
      AND METHODS: This is a cross-sectional naturalistic study of 52 inpatients (28
      females and 24 males, aged from 24 to 75 years) meeting criteria for a current
      depressive episode within Recurrent Depressive Disorder (RDD) or Bipolar Disorder
      (BD) according to ICD-10. All patients were evaluated with the Hamilton
      Depression Rating Scale (HDRS), followed by a direct interview about their
      dreams' content and emotional charge, as well as about suicidal thoughts and
      plans or previous attempts. RESULTS: Patients with RDD suffered significantly
      more frequently from nightmares than those with BD, p<0.05. Within the RDD group,
      experiencing nightmares was associated with significantly higher scores on the
      HDRS suicide risk item (2.36 vs 1.00), higher frequency of suicide attempts (35%
      vs 6%), and lower likelihood for lack of detectable suicide risk (21% vs 81%),
      p<0.05. These differences were not explained by significant difference in the
      severity of depressive symptoms (28.00 vs 24.75, p=0.16). We were unable to
      detect such differences in the bipolar subgroup. No gender influences on the
      association of nightmares and suicidal risk were observed. CONCLUSIONS: Depressed
      patients suffering from nightmares showed significantly higher suicide risk.
      Depression appeared to be a stronger risk factor for suicidal behavior when
      accompanied with nightmares. This was only valid for unipolar depression, while
      the results concerning bipolar depression were inconclusive.

PMID- 24909254
TI  - The most effective intervention for attention deficit-hyperactivity disorder:
      using continuous performance test.
AB  - BACKGROUND: This study compares the effectiveness of three treating methods
      including behavioral mother training (BMT), Verbal self-instruction to the
      children (VSI), and pharmacotherapy in children with attention deficit
      hyperactivity disorder (ADHD) using the continuous performance test (CPT).
      SUBJECTS AND METHODS: In this semi-experimental study, 51 elementary students
      were identified in a boys' school in Shiraz (age 8-10) with attention deficit
      hyperactivity disorder in a pilot study (among 1760 students). They were randomly
      divided into three groups; BMT, VSI, and control group. Moreover, 22 students
      were selected with ADHD among the clients in Hafez hospital. They were chosen by
      the availability method and they were put into the Pharmacotherapy group. Data
      collection tools were the Child Symptoms Inventory (CSI-4) and the continuous
      performance test. All of the groups were evaluated after the intervention and in
      post-test and also 2 months later in follow up. RESULTS: The treatment type
      (group) showed statistically significant difference in the result of CPT on
      severity of attention-deficit and in the number of correct responses (P=0.01),
      yet on the hyperactivity symptoms, there was no significant difference between
      the different treatment groups (P=0.08). The time factor shows a significant
      difference among the different groups (p<0.001). CONCLUSIONS: Comparison of the
      various treatments of ADHD indicates that pharmacotherapy can improve the
      severity of attention deficit and the number of correct answers of children with
      ADHD.

PMID- 24909255
TI  - Quality of life and personality traits in patients with colorectal cancer.
AB  - BACKGROUND: The aim of this study was to determine whether it is possible to
      predict quality of life in patients with colorectal cancer on the basis of
      personality dimensions from the Five-factor model. SUBJECTS AND METHODS: The
      study included 56 patients with colorectal cancer (40 men and 16 women), aged 48
      87. The following instruments were used: the Questionnaire on General Information
      and Lifestyle Habits, the Quality of Life Scale, and the Neo Five-Factor
      Inventory. RESULTS: The results of overall quality of life estimations of
      colorectal cancer patients were comparable to those of healthy people. Contrary
      to expectations, extraversion was not a significant quality of life predictor.
      Neuroticism as a personality trait was the only variable which consistently
      proved to be highly significant across analyses in the prediction of total
      quality of life, satisfaction with past life, future expectations, and comparison
      with others. Key determinants of neuroticism are a proneness to experiencing
      negative affects which makes adaptation difficult, a proneness to irrational
      ideas, reduced impulse control, ineffective coping strategies, the perception of
      poor control over oneself and others, and deeming one's own resources to be
      insufficient to adequately cope with stress, thus resulting in a more negative
      quality of life estimation. CONCLUSION: These results support the conclusion that
      cognitive-behavioral interventions aimed at changing negative attributions,
      reducing tension and negative affects, acquiring more effective coping
      strategies, strengthening perceived personal control, redefining and re
      conceptualizing quality of life, and seeking/receiving more adequate social
      support could lead to an improved quality of life in patients with colorectal
      cancer.

PMID- 24909256
TI  - Health seeking behaviour in general population with psychological symptoms.
AB  - BACKGROUND: Health seeking behaviour is a complex construct in patients with
      psychological symptoms. The aim of this study was to determine a one-month
      prevalence of psychological symptoms in Slovenian general population and to
      identify correlates of health seeking behaviour. SUBJECTS AND METHODS: This study
      was conducted in a representative sample of 1,002 randomly selected Slovenian
      citizens, stratified according to sex and age. We used a method of computer
      assisted telephone interview (CATI). The questionnaire consisted of demographic
      questions, questions about the prevalence and duration of preselected symptoms in
      the past month (irritability, nervousness), questions about the presence of
      chronic diseases, EQ-5D questionnaire and the questions on health seeking
      behaviour (self-treatment, lay advice seeking and medical advice seeking).
      RESULTS: The self-reported prevalence of psychological symptoms in the past month
      was 38.0% (381/1,002). Multivariate analysis for the presence of self-reported
      psychological symptoms revealed that female sex, higher age, the presence of
      chronic disease, primary education, lay-advice seeking, pain and the presence of
      anxiety/depression on EQ-5D questionnaire were independently associated with
      psychological symptoms. CONCLUSIONS: Psychological symptoms are a major public
      health problem in Slovenian general adult population and the self-reported
      utilization of professional health care services by Slovenian population is high.
      Other patterns such as lay referral system might have a crucial influence on the
      final decision to seek medical help.

PMID- 24909257
TI  - Metabolic syndrome and cortisol/DHEAS ratio in patients with bipolar disorder and
      schizophrenia.
AB  - The cortisol/DHEAS ratio has been found to predict different health outcomes. We
      examined the association between cortisol/DHEAS ratio and metabolic syndrome
      (MetS) in patients suffering from bipolar disorder and schizophrenia. The only
      subcomponent of MetS positively associated with the cortisol/DHEAS ratio was
      diastolic blood pressure. Possible reasons for this finding, as well as study
      limitations, are discussed. 

PMID- 24909258
TI  - Reversal of weight gain with concurrent normalization of fasting glucose and
      marked reduction in triglyceride after clozapine dose-reduction and
      simplification of other psychotropics in chronic schizophrenia: a case report.

PMID- 24909259
TI  - Association between leukaemia and X-ray in children: a nationwide study.
AB  - AIM: The frequency of employing radiography is increasing. Long-term risks of
      performing X-ray procedures on children and adolescents for medical diagnosis
      have raised significant concerns. METHODS: In this study, we adopt the case
      control methodology to evaluate the relationship between the incidence rate of
      acute leukaemia and exposure to radiation during diagnostic X-ray examinations
      for children. Based on 1998-2010 data obtained from the Taiwan Bureau of National
      Health Insurance database, we selected 58 children with leukaemia and randomly
      selected an additional 232 children as the control group. RESULTS: The mean age
      of children with leukaemia is 8.92 +/- 5.24 years. The risk of leukaemia in
      children who underwent X-ray examinations increased 2.14-fold (95% CI, 1.18
      3.87). In this study, we identified that, when undergoing X-ray examinations, the
      risk of leukaemia in children increased for both sex and age groups.
      Specifically, the relationship between leukaemia and X-ray in boys (OR = 3.28,
      95%CI, 1.33-8.07) and in ages of 6 to 11 years (OR = 2.58, 95%CI, 1.09-6.10) was
      significant. Overall, the risk of leukaemia in children who underwent X-ray
      examinations progressively increased from a ratio of 1.65 to 3.14. Moreover, an
      identical trend was observed for boys (1.85 to 6.42). CONCLUSION: Exposure to X
      ray increased the risk of leukaemia in children.

PMID- 24909260
TI  - Review article: the efficacy of biomarkers in chronic fibroproliferative diseases
      - early diagnosis and prognosis, with liver fibrosis as an exemplar.
AB  - BACKGROUND: Nearly 45% of all deaths are associated with chronic
      fibroproliferative diseases, of which the primary characteristic is altered
      remodelling of the extracellular matrix. A major difficulty in developing anti
      fibrotic therapies is the lack of accurate and established techniques to estimate
      dynamics of fibrosis, regression or progression, in response to therapy. AIM: One
      of the most pressing needs in modern clinical chemistry for fibroproliferative
      disorders is the development of biomarkers for early diagnosis, prognosis, and
      early efficacy for the benefit of patients and to facilitate improved drug
      development. The aim of this article was to review the serological biomarkers
      that may assist in early diagnosis of patients, separate fast from slow- or
      nonprogressors, and possibly assist in drug development for fibroproliferative
      diseases, exemplified by liver fibrosis. The lack of success of biochemical
      markers and the possible reasons for this is discussed in the context of other
      fields with biomarker success. METHOD: This is a personal opinion review article.
      RESULTS: Biochemical markers, originating from the fibrotic structure, may have
      increased specificity and sensitivity for disease. Assessment of the tissue
      turnover balance by measurement of tissue formation and tissue degradation
      separately by novel technologies may provide value. CONCLUSIONS: Novel
      technologies focused on the protein fingerprint in addition to biomarker
      classification, may increase the quality of biomarker development and provide the
      much needed biomarkers to further the fibroproliferative field. This is in direct
      alignment with the Food and Drug Administration and European Medicinal Agencies
      initiatives of personal health care.

PMID- 24909262
TI  - Use of the SLW index to calculate growth function in the sea cucumber
      Isostichopus badionotus.
AB  - Age and growth analysis is essential to fisheries management. Indirect methods to
      calculate growth are widely used; however, length frequency data analysis in sea
      cucumbers is complicated by high data variability caused by body wall elasticity.
      Here we calculated Isostichopus badionotus parameters of the von Bertalanffy
      growth function. In order to address bias produced by body wall elasticity, we
      compared the performance of four measurements and one compound index that
      combines different biometric parameters: the square root of the length-width
      product (SLW). Results showed that variability in length data due to body wall
      elasticity was controlled by using body length (Le) from the SLW compound index.
      Growth in I. badionotus follows a negative allometric tendency. Slow or zero
      growth periods were observed during October and November, when weather conditions
      were adverse. 

PMID- 24909261
TI  - Recurrent somatic mutation in DROSHA induces microRNA profile changes in Wilms
      tumour.
AB  - Wilms tumour (WT) is an embryonal kidney neoplasia for which very few driver
      genes have been identified. Here we identify DROSHA mutations in 12% of WT
      samples (26/222) using whole-exome sequencing and targeted sequencing of 10
      microRNA (miRNA)-processing genes. A recurrent mutation (E1147K) affecting a
      metal-binding residue of the RNase IIIb domain is detected in 81% of the DROSHA
      mutated tumours. In addition, we identify non-recurrent mutations in other genes
      of this pathway (DGCR8, DICER1, XPO5 and TARBP2). By assessing the miRNA
      expression pattern of the DROSHA-E1147K-mutated tumours and cell lines expressing
      this mutation, we determine that this variant leads to a predominant
      downregulation of a subset of miRNAs. We confirm that the downregulation occurs
      exclusively in mature miRNAs and not in primary miRNA transcripts, suggesting
      that the DROSHA E1147K mutation affects processing of primary miRNAs. Our data
      underscore the pivotal role of the miRNA biogenesis pathway in WT tumorigenesis,
      particularly the major miRNA-processing gene DROSHA. 

PMID- 24909263
TI  - Deregulated semantic cognition contributes to object-use deficits in Alzheimer's
      disease: A comparison with semantic aphasia and semantic dementia.
AB  - Executive control is impaired from the early stages of Alzheimer's Disease (AD)
      and this produces deregulated semantic cognition (Corbett, Jefferies, Burns, &
      Lambon Ralph, ; Perry, Watson, & Hodges, ). While control deficits should affect
      semantic retrieval across all modalities, previous studies have typically focused
      on verbal semantic tasks. Even when non-verbal semantic tasks have been used,
      these have typically employed simple picture-matching tasks, which may be
      influenced by abnormalities in covert naming. Therefore, in the present study, we
      examined 10 patients with AD on a battery of object-use tasks, in order to
      advance our understanding of the origins of non-verbal semantic deficits in this
      population. The AD patients' deficits were contrasted with previously published
      performance on the same tasks within two additional groups of patients,
      displaying either semantic degradation (semantic dementia) or deregulation of
      semantic retrieval (semantic aphasia; Corbett, Jefferies, Ehsan, & Lambon Ralph,
      ). While overall accuracy was comparable to the scores in both other groups, the
      AD patients' object-use impairment most closely resembled that observed in SA;
      they exhibited poorer performance on comprehension tasks that placed strong
      demands on executive control. A similar pattern was observed in the expressive
      domain: the AD and SA groups were relatively good at straightforward object use
      compared to executively demanding, mechanical puzzles. Error types also differed:
      while all patients omitted essential actions, the SA and AD groups'
      demonstrations also featured unrelated intrusions. An association between AD
      patients' object use and their scores on standard executive measures suggested
      that control deficits contributed to their non-verbal semantic deficits.
      Moreover, in a task specifically designed to manipulate executive demand,
      patients with AD (and SA) exhibited difficulty in thinking flexibly about the non
      canonical uses of everyday objects, especially when distracted by semantically
      related objects. This study provides converging evidence for the notion that a
      failure of regulatory control contributes to multimodal semantic impairment in AD
      and uniquely demonstrates this pattern for the highly non-verbal domain of object
      use. 

PMID- 24909264
TI  - Human cationic trypsinogen but not serine peptidase inhibitor, Kazal type 1
      variants increase the risk of type 1 autoimmune pancreatitis.
AB  - BACKGROUND AND AIM: Autoimmune pancreatitis (AIP) is a distinct disease entity.
      Whether the genes involved in pancreatic acinar cell injury, cationic trypsinogen
      gene (protease, serine, 1 [trypsin 1] [PRSS1]) and the pancreatic secretory
      trypsin inhibitor gene (serine peptidase inhibitor, Kazal type 1 [SPINK1]), are
      associated with AIP remains to be explored. METHODS: Genetic analyses of PRSS1
      variants (exon 2 and 3) and SPINK1 variants (exon 1, 2, and 3) including the
      intronic areas in 118 patients with AIP and 200 control subjects were performed
      by direct DNA sequencing. Clinical features including imaging, histology,
      serology, response to steroid, and extra-pancreatic organ involvement in AIP
      patients with and without variants were compared. RESULTS: A total of 19 PRSS1
      variants and one SPINK1 variant were identified in 20 (16.9%) out of 118 AIP
      patients. They included one K92N, nine R116C, seven T137M, one C139S, and one
      C139F of PRSS1 and one 2(IVS3 + 2) of SPINK1. No PRSS1 or SPINK1 variant was
      identified in the control group. Patients with PRSS1 variants had an increased
      risk of AIP with odds ratio 22.37 (95% confidence interval: 2.96-168.8, P =
      0.003) and higher frequency of serum IgG4 above 280 mg/dL. Using
      immunosuppressive agent and PRSS1 variant were predictors of less disease relapse
      in univariate analysis. Presence of PRSS1 variants was the only negative
      predictor for disease relapse in multivariate analysis. CONCLUSIONS: We found a
      significantly higher frequency of PRSS1 variants in AIP patients than in
      geographically and ethnically matched control subjects. PRSS1 variants are
      associated with less disease relapse in AIP.

PMID- 24909265
TI  - Can video thermography improve differential diagnosis and therapy between basal
      cell carcinoma and actinic keratosis?
AB  - Various noninvasive techniques (dermoscopy, confocal microscopy, etc.) have been
      introduced to help the clinical diagnosis in nonmelanoma skin cancer. Among them,
      the high definition video thermographic technique (VTG) has recently been
      proposed. The aim of this study is to define the VTG patterns, respectively of
      actinic keratosis (AK) and basal cell carcinoma (BCC), and to compare these data
      with them of dermoscopy. The study included 36 patients with a total number of
      135 lesions who underwent clinical, VTG, and dermoscopic examination. The VTG
      showed the presence of a hyperthermic pattern in all the cases of AK, while in
      the case of the BCC, the pattern was hypothermic. Dermoscopy also showed distinct
      pattern for AK and for BCC, but in 22% of them the data were not conclusive. Our
      study permits us to define two specific VTG patterns, BCC and AK respectively. 

PMID- 24909266
TI  - Mutational and expressional analysis of ERBB3 gene in common solid cancers.
AB  - ERBB3 is a member of EGFR family receptor tyrosine kinases, genetic alterations
      of which are common and therapeutically targeted in human cancers. Recently,
      somatic mutations of ERBB3 gene, including recurrent mutation in exon 3 altering
      Val104, were reported in gastric cancers (GC) and colorectal cancers (CRC),
      strongly suggesting its role in the development of GC and CRC. To examine whether
      the recurrent ERBB3 mutations of exon 3 occur in GC and CRC, and other
      malignancies as well, we analyzed the ERBB3 in 1677 cancer tissues by a single
      strand conformation polymorphism (SSCP) assay. We identified ERBB3 mutations
      altering the Val104 mutations in GC (0.5%) and CRC (2.2%). However, we did not
      find the ERBB3 mutations in the other cancers besides GC and CRC. We observed
      that an increased intensity of phosphorylated ERBB3 (pERBB3) in GC and CRC. Of
      note, all of the cancers with ERBB3 mutations displayed an increased intensity of
      pERBB3 immunostaining. Our data indicate that the recurrent ERBB3 mutations
      altering Val104 occur predominantly in GC and CRC. Also, the data suggest that
      ERBB3 is altered in GC and CRC by various ways, including somatic mutations and
      increased expression that might play roles in tumorigenesis.

PMID- 24909267
TI  - Mutations in SMARCAD1 cause autosomal dominant adermatoglyphia and perturb the
      expression of epidermal differentiation-associated genes.
AB  - BACKGROUND: Autosomal dominant adermatoglyphia (ADG) is characterized by lack of
      palmoplantar epidermal ridges. Recently, ADG was found to be caused in one family
      by a mutation in SMARCAD1, a member of the SNF subfamily of the helicase protein
      superfamily. OBJECTIVES: To investigate the genetic basis of ADG. METHODS: We
      used direct sequencing and global gene expression analysis. RESULTS: We
      identified three novel heterozygous mutations in SMARCAD1 (c.378 + 2T > C, c.378
      + 5G > C and c.378 + 1G > A) in a total of six patients. Surprisingly, all four
      ADG-causing mutations identified to date disrupt a single conserved donor splice
      site adjacent to the 3' end of a noncoding exon and are predicted to result in
      haploinsufficiency for a skin-specific isoform of SMARCAD1. These data indicate a
      pivotal role for the SMARCAD1-skin specific isoform in dermatoglyph formation. In
      order to better understand the consequences of ADG-associated mutations, we
      ascertained the global transcription profiles of primary keratinocytes
      downregulated for SMARCAD1 and of patient-derived keratinocytes. A total of eight
      genes were found to be differentially expressed in both patient-derived and
      knocked down keratinocytes. Of interest, these differentially expressed genes
      have been implicated in epidermal ontogenesis and differentiation, and in
      psoriasis, which is characterized by abnormal finger ridge patterns. CONCLUSIONS:
      The present data suggest that ADG is genetically homogeneous and result from
      perturbed expression of epidermal differentiation-associated genes.

PMID- 24909268
TI  - Stimulation of electroporation-induced inward currents in glioblastoma cell lines
      by the heat shock protein inhibitor AUY922.
AB  - Membrane electroporation (MEP) increases the electrical conductivity of the
      plasma membrane by addition of an external electrical field. Combining MEP
      induced current (IMEP ) with antineoplastic agents has been increasingly
      considered as a new therapeutic manoeuvre, especially in the treatment of
      malignant gliomas. Thus, the aim of the present study was to evaluate the effect
      of AUY922 (AUY), a potent inhibitor of heat-shock protein 90 (HSP90), on IMEP in
      glioblastoma cells. The IMEP in glioblastoma cells (U373) was generated by
      repetitive hyperpolarization from -80 to -200 mV. The amplitude of IMEP was
      increased by AUY in a concentration-dependent manner, with an EC50 of 0.32
      MUmol/L. In addition AUY shortened the latency to IMEP generation. Before
      depolarization to +50 mV, hyperpolarization to -200 mV for 50 msec produced
      Ca(2+) influx and subsequently increased the amplitude of the Ca(2+) -activated
      K(+) current (IK(Ca) ). The amplitude of IK(Ca) and Ca(2+) influx was further
      increased by AUY through its ability to activate IMEP . Other HSP90 inhibitors,
      namely 17-(allylamino)-17-demethoxygeldanamycin (17-AAG; 1 MUmol/L) and 6-chloro
      9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine (BIIB021; 1
      MUmol/L), only slightly (albeit significantly) increased the amplitude of IMEP in
      glioblastoma cells. A 50 msec depolarizing step elevated Ca(2+) influx and
      subsequently increased the amplitude of IK(Ca) in the presence of these three
      inhibitors. These data indicate that the AUY-mediated stimulation of IMEP and
      IK(Ca) in glioblastoma cells is independent of HSP90 inhibition. Moreover, these
      results indicate that AUY-stimulated IMEP and the subsequent activation of IK(Ca)
      may create important signalling events in glioblastoma cells. Thus, AUY is a drug
      that could potentially be used to augment the effectiveness of
      electrochemotherapy. 

PMID- 24909269
TI  - Dynamics of hippocampal acetylcholine release during lithium-pilocarpine-induced
      status epilepticus in rats.
AB  - The lithium-pilocarpine model is a rat model of epilepsy that mimics status
      epilepticus in humans. Here, we report changes of acetylcholine (ACh) release in
      the hippocampus before, during and after status epilepticus as monitored by
      microdialysis in unanesthetized rats. Administration of pilocarpine (30 mg/kg
      s.c.) to rats pretreated with lithium chloride (127 mg/kg i.p.) caused a massive,
      six-fold increase of hippocampal ACh release, paralleling the development of
      tonic seizures. When seizures were stopped by administration of diazepam (10
      mg/kg i.p.) or ketamine (75 mg/kg i.p.), ACh levels returned to normal.
      Extracellular concentrations of glutamate remained unchanged during this
      procedure. Administration of atropine (1 mg/kg i.p.) 2 h after pilocarpine caused
      a further increase of ACh but did not affect seizures, whereas injection of
      mecamylamine (5 mg/kg i.p.) reduced ACh levels and seizures in a delayed fashion.
      Local infusion of tetrodotoxin, 1 MUM locally) or hemicholinium (10 MUM locally)
      strongly reduced ACh release and had delayed effects on seizures. Administration
      of glucose or inositol (250 mg/kg each i.p.) had no visible consequences. In
      parallel experiments, lithium-pilocarpine-induced status epilepticus also
      enhanced striatal ACh release, and hippocampal ACh levels equally increased when
      status epilepticus was induced by kainate (30 mg/kg i.p.). Taken together, our
      results demonstrate that seizure development in status epilepticus models is
      accompanied by massive increases of extracellular ACh, but not glutamate, levels.
      Treatments that reduce seizure activity also reliably reduce extracellular ACh
      levels.

PMID- 24909270
TI  - Prescribers' practice of assessing arrhythmia risk with QT-prolonging
      medications.
AB  - AIMS: This study aimed to assess prescribers' monitoring for arrhythmic risk with
      QT-prolonging medications (LQT drugs). METHODS: Over a 6-month period, all
      inpatients under the care of Cardiologists (Cohort A) and General Physicians
      (Cohort B) at Aberdeen Royal Infirmary who were prescribed drugs with known risk
      of Torsades de Pointes (TdP) were identified. Admission and repeat
      electrocardiograms (ECG) after 48 h of commencing a LQT drug were examined.
      Actions taken if QTc was prolonged and drug-drug interactions were examined. A
      risk estimate on the UK hospital population was calculated. RESULTS: Of the 4133
      patients admitted during the study period, 234 (6%) patients were prescribed a
      LQT drug. There were 100 (43%) patients in Cohort A and 134 (57%) patients in
      Cohort B. Of those admitted with a pre-existing LQT drug prescription, an ECG was
      performed in 167 (96%) of patients and QTc prolongation was identified in 59
      (34%). Of those who received a new prescription of LQT drug, 23 (38%) had QTc
      prolongation and more patients in Cohort A than Cohort B had a repeat ECG within
      48 h (84% vs. 11%, P < 0.0001). QTc prolongation was only recognized in 6 (14%)
      and 2 (5%) patients in cohorts A and B, respectively. Only one patient at risk of
      drug interaction had QTc prolongation. None of our patients had documented TdP in
      hospital. Extrapolating these findings to the UK hospital population, at least
      204 and <17-175 patients on cardiac and noncardiac LQT drugs, respectively, might
      be expected to have TdP each year. CONCLUSION: Recognition of acquired QTc
      prolongation is poor. Clinician education and an electronic prescribing system
      may improve this situation.

PMID- 24909271
TI  - Nationwide population-based study of cause-specific death rates in patients with
      psoriasis.
AB  - BACKGROUND: Psoriasis is a common chronic disease, mediated by type 1 and 17
      helper T cell-driven inflammation. Epidemiological studies have demonstrated a
      wide range of comorbidities and increased mortality rates. However, the current
      evidence on psoriasis-related mortality is limited and nationwide data have not
      been presented previously. METHODS: In a nationwide population-based cohort we
      evaluated all-cause and cause-specific death rates in patients with psoriasis as
      compared to the general population. RESULTS: The entire Danish population aged 18
      and above, corresponding to a total of 5,458,627 individuals (50.7% female, 40.9
      years +/- 19.7), including 94,069 with mild psoriasis (53% female, 42.0 +/- 17.0
      years) and 28,253 with severe psoriasis (53.4% female, 43.0 +/- 16.5 years), was
      included. A total of 884,661 deaths were recorded, including 10 916 in patients
      with mild psoriasis and 3699 in patients with severe psoriasis. The age at time
      of death varied by psoriasis status, i.e. 76.5 +/- 14.0, 74.4 +/- 12.8 and 72.0
      +/- 13.4 years, for the general population, mild psoriasis and severe psoriasis
      respectively. In general, the highest death rates were observed in patients with
      severe psoriasis. Overall death rates per 1000 patient years were 13.8
      [confidence interval (CI) 13.8-13.8], 17.0 (CI 16.7-17.3) and 25.4 (CI 24.6-26.3)
      for the general population, patients with mild psoriasis and patients with severe
      psoriasis respectively. CONCLUSION: This nationwide population-based study of
      cause-specific death rates in patients with psoriasis demonstrated reduced
      lifespan and increased rates of all examined specific causes of death in patients
      with psoriasis compared to the general population.

PMID- 24909272
TI  - [Preparation of lentivirus containing human FcgammaRIIB gene and FcgammaRIIB
      expression in HT-1080 cells].
AB  - OBJECTIVE: To construct a lentiviral expression vector for FcgammaRIIB and
      identify its expression in HT-1080 cells. METHODS: FcgammaRIIB gene fragment was
      obtained using reverse transcription with human mRNA as the template, and then
      was cloned into TRE lentiviral expression plasmid to construct the lentiviral
      expression recombinant plasmid TRE-FcgammaRIIB. The recombinant plasmid TRE
      FcgammaRIIB and lentiviral inducible plasmid Tet were transfected into HEK293T
      cells respectively with lentivirus packaging mix plasmids to pack the expression
      lentivirus and inducible lentivirus. The viral titers of the two lentiviruses
      were measured respectively. HT-1080 cells were coinfected with the expression
      lentivirus and the inducible lentivirus and induced by gradient-concentration
      doxycycline (Dox). The expression of FcgammaRIIB was detected by
      immunofluorescence technique. Real-time quantitative PCR (qRT-PCR) and Western
      blotting were used to detect FcgammaRIIB mRNA and protein expression levels,
      respectively. RESULTS: The recombinant plasmid was identified using PCR assay and
      enzyme digestion analysis, and gene sequencing demonstrated that the nucleotide
      sequence of the inserted fragment had a homology of 100% with the FcgammaRIIB
      nucleotide sequence provided by GenBank. The virus titer of the expression
      lentivirus was 10(6) TU/mL and the inducible lentivirus was 10(5) TU/mL. The
      immunofluorescence technique showed that the HT-1080 cells co-infected by
      expression lentivirus and inducible lentivirus expressed FcgammaRIIB under the
      induction of Dox. The qRT-PCR and the Western blotting showed that FcgammaRIIB
      mRNA and protein expression levels were positively correlated with the
      concentration of Dox. CONCLUSION: The lentiviral expression vector for
      FcgammaRIIB was successfully prepared and its expression in HT-1080 cells is
      controllable via the alterations of Dox concentration.

PMID- 24909273
TI  - [Ginsenoside Rh2 inhibits proliferation and promotes apoptosis of leukemia KG1
      alpha cells].
AB  - OBJECTIVE: To investigate the effect of ginsenoside Rh2 on leukemia KG1-alpha
      cells. METHODS: KG1-alpha cells were cultured in 96-well plate and harvested in
      the exponential phase. The cells were induced in the presence of different
      concentrations of Rg1, Rb1, Rh2 respectively for 24, 48, 72 hours. The
      conventional culture was performed in blank control group, and cytarabine
      hydrochloride as the positive control. The inhibitory effects of ginsenoside Rb1,
      Rg1, Rh2 on the growth of KG1-alpha cells were tested by CCK-8 assay. Then the
      most efficient ginsenoside was chosen for the further study by IC50. The effects
      of the ginsenoside Rh2 on cell cycle and apoptosis were detected by flow
      cytometry (FCM) combined with PI staining and annexin V-FITC/PI, respectively.
      The expressions of P53, P21, cyclin D1 and cleaved-caspase-3 were examined by
      Western blotting. RESULTS: CCK-8 assay results showed that IC50 of ginsenoside
      Rh2, ginsenoside Rb1, ginsenoside Rg1 and cytarabine were 75, 207, 268, 1058
      MUmol/L, respectively. Compared with those in blank control group, the KG1-alpha
      cells after treated with 75 MUmol/L ginsenoside Rh2 showed up-regulated apoptosis
      rates from (5.37+/-0.02)% to (8.37+/-0.015)% at 24 hours and to (33.22+/-1.67)%
      at 48 hours (P<0.05). In addition, the percentage of cells in G0/G1 phase
      increased significantly from (26.78+/-3.14)% to (29.26+/-2.31)% at 24 hours and
      to (44.77+/-2.26)% at 48 hours, and the percentage in S phase decreased
      significantly from (65.43+/-2.22)% to (51.46+/-0.57)% and (48.29+/-1.80)%,
      respectively. The expression levels of cleaved-caspase 3, P53 and P21 proteins
      went up significantly when the cells were treated with 75 MUmol/L Rh2(P<0.05),
      meanwhile cyclin D1 protein dropped significantly (P<0.05). CONCLUSION:
      Ginsenoside Rh2 could inhibit the proliferation of KG1-alpha cell and prompt its
      apoptosis.

PMID- 24909274
TI  - [Oxygen glucose deprivation induced glutamate release in primary cultured
      astrocytes].
AB  - OBJECTIVE: To investigate the effect of oxygen glucose deprivation (OGD) on the
      glutamate release and the role of connexin 43 (Cx43) hemichannels in the OGD
      induced glutamate release in primary cultured astrocytes. METHODS: The astrocytes
      were randomly divided into four groups: normal control, OGD group, Gap26 (Cx43
      hemichannel blocker) plus OGD group, Cx43-specific antisense oligodeoxynucleotide
      (ASODN) plus OGD group. In the OGD group, the astrocytes were cultured in the
      oxygen- and glucose-free culture medium (950 mL/L N2 and 50 mL/L CO2) for
      different durations (0, 15, 30, 60, 90, 120 minutes) at 37 Degrees Celsius, while
      the astrocytes in the control group were cultured in the ordinary culture medium.
      In the Gap26 plus OGD group or Cx43-ASODN plus OGD group, the astrocytes were
      incubated with Gap26 or Cx43-ASODN before and during the OGD. The extracelluar
      glutamate level was measured by high performance liquid chromatography (HPLC).
      RESULTS: After OGD, the extracelluar glutamte level significantly increased, and
      reached the maximum (5.00+/-0.30) nmol/mL at 90 minutes of OGD, which was
      significantly higher than that of the normal control (2.36+/-0.15)
      nmol/mL(P<0.05). After treatment by Cx43-ASODN or Gap26, the increase was
      inhibited. At 90 minutes of OGD, the extracellular glutamate levels were
      respectively (4.02+/-0.18) nmol/mL and (3.93+/-0.32) nmol/mL. They were
      signficalty lower than that of the OGD group at the same time (P<0.05).
      CONCLUSION: OGD induced glutamate release through Cx43 hemichannel in primary
      cultured astrocytes.

PMID- 24909275
TI  - [Construction and identification of a prokaryotic expression vector for Zmp1 gene
      from Mycobacterium tuberculosis].
AB  - OBJECTIVE: To construct a prokaryotic expression plasmid for zinc-dependent
      metalloprotease-1 (Zmp1) gene from Mycobacterium tuberculosis and express the
      plasmid in E.coli. METHODS: Zmp1 gene was amplified by PCR using the genome of
      Bacillus Calmette-Guerin vaccine (BCG) as a template and inserted into a multiple
      cloning site of prokaryotic expression vector pET32a(+). The constructed
      prokaryotic expression vector pET32a+/-Zmp1 was transformed into E.coli
      BL21(DE3), and the recombinant proteins were expressed via IPTG induction.
      Finally, the expression of Zmp1 protein was detected by SDS-PAGE and Western
      blotting. RESULTS: Restriction analysis and sequencing proved that the
      recombinant plasmid pET-32a+/-Zmp1 was constructed correctly. The relative
      molecular mass of the expressed recombinant protein was about 94 000 which was
      the same with that of presumed fusion protein. Recombinant Zmp1 protein showed a
      specific binding to monoclonal antibody with His tag. CONCLUSION: The prokaryotic
      expression vector for Zmp1 gene was successfully constructed and the Zmp1 fusion
      protein was effectively expressed in E. coli BL21(DE3).

PMID- 24909276
TI  - [Evaluation of immunological efficiency induced by Campylobacter jejuni PEB1 DNA
      combined with PEB1 protein in mice].
AB  - OBJECTIVE: To explore the improved immunological responses induced by an amino
      acid ABC transporter, permease protein PEB1 DNA vaccine primer-protein boost
      immunization method against Campylobacter jejuni. METHODS: The DNA vaccine
      pcDNA3.1(-)-PEB1 and protein vaccine were prepared, respectively. The female
      BALB/c mice were intranasally immunized with the vaccines. PBS and pcDNA3.1(-)
      were used as controls. The humoral and cellular immunological responses were
      detected in female BALB/c mice that were challenged by Campylobacter jejuni at 28
      days after the final immunization. RESULTS: In the DNA primer-protein boost group
      at day 56, the stimulation index (SI) of lymphocytes was 2.625+/-0.275, serum IgG
      was (2.507+/-0.124) MUg/mL, IL-4 in spleen supernatant was (377.47+/-14.560)
      pg/mL, IFN-gamma in spleen supernatant was (258.920+/-13.472) pg/mL, and sIgA in
      genital tract was (80.351+/-5.769) ng/mL. All of them were significantly higher
      than those in controls (P<0.05). The DNA primer-protein boost vaccines induced
      the strongest levels of protection to BALB/c mice (91.53%). CONCLUSION: The DNA
      primer-protein boost immunization could induce significant protective immunity
      against Campylobacter jejuni challenge. It could significantly enhance both
      humoral and cellular immunologic responses in BALB/c mice, compared with DNA
      vaccine or protein vaccine immunization alone.

PMID- 24909277
TI  - [Preparation of an autophagy-targeted antituberculosis DNA vaccine encoding LpqH
      fused with LC3].
AB  - OBJECTIVE: To construct an autophagy-targeted vaccine harboring the genes
      encoding lipoprotein antigen precursor LpqH from Mycobacterium tuberculosis and
      microtubule-associated protein light chain-3(LC3), and to investigate its
      efficacy of inducing and targeting autophagy. METHODS: The expressions of LC-3
      and LC3-LpqH in RAW264.7 cells were detected by Western blotting after
      transfected with pCMV-LpqH and pCMV-LC3-LpqH plasmids respectively. The pCMV-LC3
      LpqH or pCMV-LpqH plasmids were transfected into GFP-LC3-RAW264.7 cells to
      analyze the localization of LC3-LpqH by immunofluorescence staining. RESULTS:
      After transfected with pCMV-LpqH DNA, RAW264.7 cells showed a significant
      increase of LC-3 amount. The LC3-LpqH fusion protein was also detected in
      RAW264.7 cells after pCMV-LC3-LpqH transfection and in a dose-dependent manner.
      Interestingly, LpqH was found to be transported to autophagosomes through the
      fusion protein, which was demonstrated by the co-localization of GFP-LC3 and LC3
      LpqH on autophagosomes. CONCLUSION: The recombinant plasmid encoding pCMV-LC3
      LpqH could enhance the autophagy in vitro, and facilitate the localization of
      LpqH on autophagosomes. Our study provides a new practical strategy for the
      development of improved vaccines against Mycobacterium tuberculosis.

PMID- 24909278
TI  - [Down-regulation of CD59 inhibits proliferation and promotes apoptosis of HeLa
      cells].
AB  - OBJECTIVE: To intervene the expression of CD59 on cervical cancer HeLa cells by
      RNA interference and phage display random peptide library, respectively, and
      detect the effect of down-regulated CD59 expression on proliferation and
      apoptosis of the cervical cancer cells. METHODS: HeLa cells were divided into
      normal control group, CD59 peptide seal group, pSUPER transfected group and
      pSUPER-siCD59 transfected group. The CD59 peptide seal group was treated with 10
      MUg/mL CD59 peptide seal for 8 hours. The pSUPER and pSUPER-siCD59 transfected
      groups were transfected with empty plasmid pSUPER and recombinant plasmid pSUPER
      siCD59, respectively. MTT assay was used for the detection of cell proliferation.
      TUNEL, annexin V-PE/7-AAD staining combined with flow cytometry were adopted for
      the detection of cell apoptosis. RESULTS: Compared with the control groups, both
      CD59 peptide seal group and pSUPER-siCD59 transfected group presented a
      diminished cell proliferation activity and a strengthened apoptosis. What's more,
      the effect of peptide seal on CD59 expression inhibition was better than that of
      pSUPER-siCD59 plasmid. CONCLUSION: Down-regulation of CD59 expression could
      inhibit HeLa cells' proliferation and promote apoptosis, and the inhibitory
      effect of peptide seal was better than that of CD59 interference plasmid.

PMID- 24909279
TI  - [Construction and identification of luciferase and EGFP expression vectors
      containing human IFN-beta promoter].
AB  - OBJECTIVE: To construct a luciferase expression vector (pGL3-IFNB1) and an
      enhanced green fluorescent protein expression vector (pGE3-IFNB1) containing
      human IFN-beta promoter, and verify the promoter activity of IFN-beta in A549
      cells. METHODS: IFN-beta promoter was amplified with the human genome DNA by PCR,
      then the segment was cloned into the eukaryotic expression vectors pGL3-basic and
      pGE3-basic by PCR. The eukaryotic expression vectors were named pGL3-IFNB1 and
      pGE3-IFNB1, respectively. The recombinant vectors were then transiently
      transfected into A549 cells respectively, and 6 hours later, the transfected
      cells were infected with Hantaan virus (HTNV). After 24 hours, the expressions of
      pGL3-IFNB1 and pGE3-IFNB1 were tested in A549 cells. RESULTS: Double restriction
      enzyme digestion and sequence analysis showed that the recombinant vectors were
      successfully constructed and expressed in A549 cells correctly. After HTNV
      infection, stronger expression was observed in these cells. CONCLUSION: The
      recombinant vectors pGL3-IFNB1 and pGE3-IFNB1 containing IFN-beta promoter have
      been successfully constructed. It provides useful tools for further study on the
      mechanism of IFN-beta production induced by virus.

PMID- 24909280
TI  - [Combined inhibition of PI3K and MEK has synergistic inhibitory effect on the
      proliferation of cisplatin-resistant ovarian cancer cells].
AB  - OBJECTIVE: To investigate the effect of phosphatidylinositol 3 kinase (PI3K)
      inhibitor LY294002 combined with mitogen activated protein kinase kinase (MEK)
      inhibitor AZD6244 on the proliferation of cisplatin-resistant SKOV3/DDP ovarian
      cancer cell line. METHODS: The alteration in the cell proliferation of SKOV3/DDP
      cells treated with 5, 10, 20, 40, 80 MUmol/L LY294002 and 1, 2, 4, 8, 16 MUmol/L
      AZD6244 alone or together, was detected by MTT assay. The 50% inhibitory
      concentration (IC50) and combined index (CI) were calculated. The concentration
      of the combination was obtained based on the MTT assay, and the cells were
      divided into four groups: the control group, LY294002 group (5 MUmol/L), AZD6244
      group (7 MUmol/L) and combination group (LY294002 5 MUmol/L and AZD6244 7
      MUmol/L); Forty-eight hours later, MTT assay was used to detect the cell
      proliferation and calculate cell doubling time; colony formation assay was
      performed to detect colony formation efficiency; Annexin V-PE/7-ADD staining
      combined with flow cytometry (FCM) was used to detect the apoptotic rates and
      cell cycle; Western blotting was employed to detect the levels of AKT,
      phosphorylated AKT (p-AKT), extracellular signal-regulated kinase 1/2 (ERK1/2),
      phosphorylated ERK1/2 (p-ERK1/2), cyclin D1 and cleaved caspase-3 protein.
      RESULTS: Cell growth was inhibited by LY294002 or AZD6244 alone, and the effect
      was strengthened when LY294002 was combined with AZD6244 (CI<1), indicating that
      the two inhibitors showed synergistic effect. The proliferation of cells was
      significantly slower, the cell doubling time was significantly prolonged, and
      colony number was reduced in the combined treatment group (P<0.01) compared with
      the single inhibitor treatment group and the control group. Meanwhile, FCM
      demonstrated that the apoptotic rate of the combination group was significantly
      higher than that of the other groups, and the cells significantly increased in G1
      phase and decreased in S phase (P<0.05). As Western blotting showed, there were
      no differences in the expressions of AKT and ERK1/2 protein among the four groups
      (P>0.05); in the LY294002 treatment group, the level of p-AKT protein decreased
      and p-ERK increased; in the AZD6244 group, the level of p-ERK1/2 protein
      decreased and p-AKT increased; in the combination group, the levels of p-AKT, p
      ERK1/2 and cyclin D1 protein were significantly inhibited, while cleaved caspase
      3 protein was up-regulated. CONCLUSION: Combined PI3K inhibitor LY294002 and MEK
      inhibitor AZD6244 has synergistic effect on inhibition of SKOV3/DDP cell growth
      by inducing apoptosis and blocking cell cycle.

PMID- 24909281
TI  - [miR-497 suppresses proliferation of human cervical carcinoma HeLa cells by
      targeting cyclin E1].
AB  - OBJECTIVE: To evaluate the effect of miR-497 on proliferation of human cervical
      carcinoma HeLa cells and target relationship between miR-497 and cyclin E1
      (CCNE1). METHODS: Pre-miR-497 sequences were synthesized and cloned into
      pcDNATM6.2-GW to construct recombinant plasmid pcDNATM6.2-GW-pre-miR-497 and
      identified by real-time quantitative PCR (qRT-PCR). In addition, sequences of the
      wild-type CCNE1 (WT-CCNE1) and mutant CCNE1 (MT-CCNE1) were respectively cloned
      into pmirGLO vectors. MTT assay was used to explore the impact of miR-497 on the
      proliferation of HeLa cells. Furthermore, the target effect of miR-497 on the
      CCNE1 was identified by dual-luciferase reporter assay system, qRT-PCR and
      Western blotting. RESULTS: The recombinant plasmids pcDNATM6.2-GW-pre-miR-497 and
      pmirGLO-WT-CCNE1, pmirGLO-MT-CCNE1 were successfully constructed, and the miR-497
      expression level in HeLa cells transfected with pre-miR-497 was significantly
      higher than that in the neg-miR group (P<0.05). MTT assay showed that miR-497
      could significantly inhibit the proliferation of HeLa cells (P<0.05). A
      remarkable reduction of luciferase activities of WT-CCNE1 reporter was observed
      in HeLa cells with pre-miR-497 transfection (P<0.01), and the mRNA and protein
      expression levels of CCNE1 were down-regulated in HeLa cells transfected with pre
      miR-497 (P<0.05). CONCLUSION: Over-expressed miR-497 in HeLa cells could suppress
      cell proliferation by targeting CCNE1.

PMID- 24909282
TI  - [Effect of IL-17A on levels of antiheart autoantibodies in mice with viral
      myocarditis].
AB  - OBJECTIVE: To explore the effect of interleukin-17A (IL-17A) on the serum level
      of antiheart autoantibodies in mice with viral myocarditis. METHODS: Male wild
      type (WT) and IL-17A-deficient (IL-17A(-/-)) BALB/c mice were intraperitoneally
      injected with Coxsackie virus B3 (CVB3) for establishing VMC models (VMC-WT group
      and VMC-IL-17A(-/-) group). Meanwhile, a control group (WT group) of WT mice were
      established by i.p. administration of phosphate buffered saline (PBS). Paraffin
      sections of cardiac tissues were made 14 days after CVB3 injection. Myocardial
      histopathologic changes were evaluated by HE staining. The levels of anti-adenine
      nucleotide translocator (ANT) autoantibody, anti-beta-myosin heavy chain (beta
      MHC) autoantibody and anti-cardiac L-type calcium channel (CACH2) autoantibody in
      sera were measured by ELISA. RESULTS: Compared with WT group, the levels of anti
      ANT-autoantibody and anti-beta-MHC-autoantibody significantly increased in VMC-WT
      group (P<0.01, P<0.05), while the concentration of anti-CACH2-autoantibody showed
      no significant difference between WT and VMC-WT groups (P>0.05). Compared with
      VMC-WT group, the level of anti-ANT-autoantibody was reduced in VMC-IL-17A(-/-)
      group (P<0.05), while the levels of anti-beta-MHC-autoantibody and anti-CACH2
      autoantibody showed no significant difference between them (P>0.05). CONCLUSION:
      IL-17A contributed to the secretion of anti-ANT-autoantibody of VMC mice, but had
      no effect on the secretion of anti-beta-MHC-autoantibody and anti-CACH2
      autoantibody in VMC mice.

PMID- 24909283
TI  - [Role of molecular adjuvants TBhsp and MT in the preparation of monoclonal
      antibody against phosphatase of regenerating liver-3].
AB  - OBJECTIVE: To explore the adjuvant effects of Mycobacterium tuberculosis heat
      shock protein (TBhsp) and Mycobacterium tuberculosis T cell stimulatory epitope
      (MT) in the preparation of the monoclonal antibody (mAb) against phosphatase of
      regenerating liver-3 (PRL-3). METHODS: The prokaryotic expression vectors pET28a
      were used for the construction of pET28a-PRL-3 (control plasmids), pET28a-PRL-3
      MT, pET28a-TBhsp-PRL-3 and pET28a- TBhsp-PRL-3-MT (recombinant plasmids). The
      various fusion proteins expressed in bacteria were purified and utilized to
      immunize the BALB/c mice, respectively. The serum level of specific anti-PRL-3
      antibody was measured by ELISA. The mouse with the highest serum level of anti
      PRL-3 antibody was selected to prepare mAb with hybridoma technique. The
      subclasses of mAb were identified. RESULTS: The PRL-3 fusion proteins expressed
      from the four expression plasmids were purified successfully. The serum level of
      anti-PRL-3 antibody from the mice immunized with PRL-3-MT was the highest
      compared with the other immune groups. Ten hybridoma cell lines secreting anti
      PRL-3 mAb were obtained after cell fusion and ELISA primary screening, and all of
      the mAb subclasses were IgG. CONCLUSION: MT is a potentially effective molecular
      adjuvant in preparation of mAb specific for PRL-3.

PMID- 24909284
TI  - [Expression and polyclonal antibody preparation of HPV-11E7 protein].
AB  - OBJECTIVE: To express human papillomavirus type 11, E7 protein (HPV11E7) via a
      prokaryotic expression vector and produce anti-HPV11E7 polyclonal antibody.
      METHODS: A prokaryotic expression vector pGEX-4T2-HPV11E7 was constructed and
      soluble GST-HPV11E7 fusion protein was expressed in E.coli by IPTG induction and
      purified. The purified HPV11E7 protein was used to immunize New Zealand rabbits
      to prepare the anti-HPV11E7 polyclonal antibody followed by protein G agarose
      purification to obtain the IgG type polyclonal antibody. Western blotting and
      immunofluorescence analysis were used to test the specificity and titer of the
      antibody. RESULTS: SDS-PAGE analysis demonstrated that large amounts of soluble
      GST-HPV11E7 fusion protein was expressed in E.coli after 6 hours of IPTG
      induction. Western blotting and immunofluorescence confirmed that the purified
      anti-HPV11E7 polyclonal IgG antibody obtained from immunized rabbits had a high
      titer and specificity. CONCLUSION: The prokaryotic expression system could
      express a great deal of soluble HPV11E7 protein, and anti-HPV11E7 polyclonal IgG
      antibody from HPV11E7-immunized rabbits was proved to have a high titer and
      specificity.

PMID- 24909285
TI  - [Preparation and characterization of polyclonal antibody against Ia-associated
      invariant chain of Muscovy Duck (Cairina moschata)].
AB  - OBJECTIVE: To prepare polyclonal antibody against invariant chain of Muscovy duck
      (Cairina moschata) (MDIi) and identify its reaction with MDIi extracted from
      tissues of Muscovy duck. METHODS: MDIi was amplified by PCR and used to construct
      the prokaryotic expression vector of pET-32a/MDIi by linking with the plasmid of
      pET-32a. Then pET-32a/MDIi was transformed into E.coli Rosetta to induce the
      prokaryotic expression. After identified by SDS-PAGE, prokaryotic expression
      products were further purified from running gel of SDS-PAGE and injected into
      mice to prepare polyclonal antibody against MDIi. The titer and specificity of
      the polyclonal antibody against MDIi were analyzed by indirect ELISA and Western
      blotting, respectively. The intensity of reaction between the polyclonal antibody
      and MDIi extracted from tissues of Muscovy duck was also identified by indirect
      ELISA. RESULTS: The prokaryotic expression vector pET-32a/MDIi was successfully
      constructed. About 40 kD recombinant proteins of MDIi were confirmed to be
      expressed in the form of inclusion body in Rosetta. Polyclonal antibody against
      MDIi with a titer of 1:128 000 was obtained from the immunized mice and its high
      specificity was demonstrated by Western blotting. The titer of reaction between
      the polyclonal antibody and MDIi was 1:32 000. CONCLUSION: The polyclonal
      antibody against MDIi was successfully prepared with a high titer and
      specificity. It has a strong immune reaction with MDIi extracted from tissues of
      Muscovy duck.

PMID- 24909286
TI  - [Detection of lymphocyte subsets in the peripheral blood of patients with
      malignant ovarian tumors].
AB  - OBJECTIVE: To investigate the relationships and implications between the various
      immune cell subsets in the peripheral blood of patients with ovarian cancer and
      the clinicopathological parameters. METHODS: Flow cytometry (FCM) was used to
      test the regulatory T cells (Tregs), helper T cells (Th1 cells), dendritic cells
      (DCs), natural killer (NK) cells and other immune cell subsets in the pre
      operative peripheral blood and ascites of 24 patients with malignant ovarian
      tumors. Then, the results were compared with those in the peripheral blood of 20
      healthy women, and their relationships with the clinicopathological parameters
      were analyzed statistically. RESULTS: Compared with the control group, there were
      an elevated level of Tregs, significantly reduced levels of Th1 cells and
      activated receptor NKG2D on CD8+ T cells (P<0.05) in the peripheral blood of the
      24 patients with ovarian cancer, which were correlated with pathological staging
      (P<0.05). The total DCs were not significantly different between healthy controls
      and ovarian cancer patients, but mature DCs (mDCs) were reduced and plasmacytoid
      DCs (pDCs) increased in the peripheral blood of the patients with ovarian cancer.
      The degree of the decreased mDCs was related to clinical stage, and the degree of
      the increased pDCs was correlated with pathological grade (P<0.05). Besides,
      compared with peripheral blood, the levels of CD16 on NK cells and NKG2D receptor
      on CD8+ T cells dropped in ascites. CONCLUSION: The anti-tumor immune function
      declined in patients with malignant ovarian tumors, and the immune functions of
      the tumor-killing effect T cells and NK cells in the peripheral blood and ascites
      of the patients were both significantly inhibited, meanwhile, the antigen
      presentation of DCs was descended.

PMID- 24909287
TI  - [Establishment of a lentivirus-mediated rapid eukaryotic expression system of
      novel avian influenza H7N9 virus hemagglutinin gene].
AB  - OBJECTIVE: To establish a rapid eukaryotic expression system of hemagglutinin
      (HA) gene of novel avian influenza H7N9 using lentiviral vector, express the
      recombinant protein and study its functions in human embryonic kidney HEK293T
      cells. METHODS: The full-length HA gene was amplified from H7N9 genomic RNA by
      reverse transcription PCR (RT-PCR) and linked with pMD18-T vector to generate
      pMD18-T-HA plasmid. Blunt-end HA gene with Kozak sequence was amplified from
      pMD18-T-HA vector, and then pLenti-HA-V5 expression vector was constructed by
      Topo cloning for transient expression in HEK293T cells. Expression of HA-V5
      recombinant protein was confirmed by immunofluorescence assay (IFA) and Western
      blotting. Hemagglutination test was performed to evaluate the biological activity
      of the recombinant protein. RESULTS: The full-length HA gene (1 683 bp) was
      obtained and eukaryotic expression plasmid was constructed successfully. A
      recombinant protein with relative molecular mass (Mr) 70 000 was expressed and
      the antigenicity and binding specificity to positive serum were demonstrated by
      IFA and Western blotting. The hemagglutination activity was proved by
      hemagglutination test. IFA and Western blotting showed that the Mr 70 000
      recombinant protein had an immuoreactivity to positive serum. The
      hemagglutination activity was confirmed by hemagglutination test. CONCLUSION: The
      rapid eukaryotic expression system of HA gene was successfully constructed, which
      laid a solid foundation for further research on subunit vaccine development,
      neutralizing epitope mapping and packaging pseudovirus.

PMID- 24909288
TI  - [Triptolide inhibits the inflammatory response of monocytes from rheumatoid
      arthritis patients by regulating miR-155].
AB  - OBJECTIVE: To explore the anti-inflammatory effect of triptolide (TPT) by
      regulating miR-155 in monocytes pre-stimulated by lipopolysaccharide (LPS) from
      rheumatoid arthritis (RA) patients. METHODS: Monocytes were isolated by CD14+
      magnetic beads from peripheral blood mononuclear cells (PBMCs) of RA and
      stimulated by LPS for 24 hours. The levels of tumor-necrosis factor-alpha (TNF
      alpha) and interleukin 6 (IL-6) in monocytes were detected by ELISA and the
      expression of miR-155 was measured by real-time quantitative PCR (qRT-PCR) in
      monocytes before and after the treatment of TPT at different concentrations. MiR
      155 mimic and negative control were respectively transfected into the LPS
      stimulated monocytes by Lipofectamine(TM)2000. Twenty-four hours later, the
      monocytes were treated with or without TPT for another 24 hours. TNF-alpha and IL
      6 expressions in the cell culture supernatants were detected by ELISA and the
      expressions of suppressor of cytokine signaling-1 (SOCS1) and Src homology 2
      domain-containing inositol 5-phosphatase 1 (SHIP-1) were tested by Western
      blotting. RESULTS: TPT suppressed the expressions of TNF-alpha, IL-6 and miR-155
      in LPS-stimulated peripheral blood monocytes from RA patients. Over-expression of
      miR-155 significantly reversed the down-regulation of TNF-alpha and IL-6 by TPT
      in monocytes. TPT up-regulated the expressions of SOCS1 and SHIP-1 in monocytes,
      but over-expressed miR-155 antagonized the effect of TPT on SHIP-1 while the
      expression of SOCS1 was not affected. CONCLUSION: TPT suppressed the expression
      of miR-155 and up-regulated the release of SHIP-1, thus inhibiting the
      inflammatory response in the LPS-stimulated monocytes of RA patients.

PMID- 24909289
TI  - [The decline in lung function is associated with a decrease in the number of
      BTLA+ lymphocytes and regulatory T cells in patients with rheumatism].
AB  - OBJECTIVE: To investigate the relationships between B, T lymphocyte attenuator
      (BTLA), regulatory T (Treg) cells and reduced lung function of patients with
      rheumatism. METHODS: The lung function of 482 patients of rheumatism, including
      rheumatoid arthritis (RA, 198 cases), ankylosing spondylitis (AS, 114 cases),
      Sjogren's syndrome (SS, 102 cases) and osteoarthritis (OA, 68 cases), were
      detected by spirometer. BTLA and Treg cells of peripheral blood in 482 patients
      with rheumatic diseases were observed using flow cytometry. RESULTS: Lung
      function and the expressions of BTLA and Treg cells were lower in patients with
      rheumatism than those in normal controls. Lung function parameters, such as
      forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), forced
      expiratory flow at 50% of forced vital capacity (FEF50), forced expiratory flow
      at 75% of forced vital capacity (FEF75), were higher in the rheumatism group with
      normal BTLA and Treg cells than those in the group with abnormal BTLA and Treg
      cells (P<0.05 or P<0.01). Correlation analysis showed that there were positive
      correlations between lung function parameters orced vital capacity(FVC), maximal
      voluntary ventilation (MVV), FEV1, forced expiratory flow at 25% of forced vital
      capacity (FEF25), FEF50 and BTLA, Tregs. There were negative correlations between
      lung function parameters FVC, FEV1, FEF50, FEF75 and IL-4, IgA, IgM (P<0.05 or
      P<0.01). CONCLUSION: The decline in lung function of patients with rheumatism is
      related to down-regulation of BTLA, Tregs and excessively abnormal activation of
      T and B cells.

PMID- 24909290
TI  - [ABO blood group genotyping based on amplification refractory mutation system].
AB  - OBJECTIVE: To develop a rapid, cost-effective and reliable method for ABO
      genotyping. METHODS: Six pairs of primers were designed for the amplification
      refractory mutation system (ARMS). Thirty peripheral blood DNA samples, derived
      from Chinese Han unrelated individuals, were genotyped by ARMS. The results were
      compared with the corresponding data obtained from serological methods and DNA
      sequencing. RESULTS: The ABO genotyping results using ARMS were perfectly in line
      with the serological methods and DNA sequencing. CONCLUSION: The method developed
      and optimized in this study is able to accurately and rapidly detect 28 kinds of
      ABO genotypes, indicative of a new approach applicable to clinical practice.

PMID- 24909291
TI  - Do we really need to keep redesigning beta2-agonists for the management of
      asthma?
AB  - There is an enormous drive to refine therapeutic designs and delivery systems,
      but in this review we ask if this is always the right direction? We choose to
      play devil's advocate, and argue that refining drug design is not always needed,
      and what is actually needed is a greater understanding of the biology of the
      disease. Here we focus on asthma and the beta2-agonist group of bronchodilators
      as an example of how a class of therapeutic has been developed and continues to
      be developmentally refined. In this review, we define viral-induced exacerbations
      as the greatest cause of lung attacks and the most crucial time beta2-agonist
      therapy is needed. We explore the reasons why beta2-agonist therapy fails in
      patients with rhinovirus-induced exacerbations, and explain why further
      "engineered" beta2-agonist therapies are likely to continue to fail in this
      subset of asthmatic population. We justify our perspective by returning to the
      biology that underlies the cause of disease and highlight the need for "more
      research" into alternative therapies for this population of asthmatic patients.

PMID- 24909292
TI  - Research to policy and practice change: is capacity building in operational
      research delivering the goods?
AB  - OBJECTIVES: Between 2009 and 2012, eight operational research capacity building
      courses were completed in Paris (3), Luxembourg (1), India (1), Nepal (1), Kenya
      (1) and Fiji (1). Courses had strict milestones that were subsequently adopted by
      the Structured Operational Research and Training InitiaTive (SORT IT) of the
      World Health Organization. We report on the numbers of enrolled participants who
      successfully completed courses, the number of papers published and their reported
      effect on policy and/or practice. DESIGN: Retrospective cohort study including a
      survey. METHODS: Participant selection criteria ensured that only those proposing
      specific programme-related and relevant operational research questions were
      selected. Effects on policy and/or practice were assessed in a standardised
      manner by two independent reviewers. RESULTS: Of 93 enrolled participants from 31
      countries (14 in Africa, 13 in Asia, two in Latin America and two in South
      Pacific), 83 (89%) completed their courses. A total of 96 papers were submitted
      to scientific journals of which 89 (93%) were published and 88 assessed for
      effect on policy and practice. There was a reported effect in 65 (74%) studies
      including changes to programme implementation (27), adaptation of monitoring
      tools (24) and changes to existing guidelines (20). CONCLUSION: Three quarters of
      published operational research studies from these structured courses had reported
      effects on policy and/or practice. It is important that this type of tracking
      becomes a standard component of operational research and research in general.

PMID- 24909293
TI  - Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type 2
      diabetes inadequately controlled by diet and exercise.
AB  - AIMS: To evaluate the efficacy and safety of the selective sodium glucose co
      transporter 2 inhibitor dapagliflozin in Japanese patients with type 2 diabetes
      mellitus (T2DM) inadequately controlled by diet and exercise. METHODS: Patients
      received placebo or dapagliflozin (5 or 10 mg) once daily for 24 weeks. The
      primary outcome measure was change from baseline in glycated haemoglobin (HbA1c).
      RESULTS: Patients (N = 261) had modestly elevated baseline HbA1c (mean ~ 7.5%)
      and most had mild or moderate renal impairment (estimated glomerular filtration
      rate range 43-103 ml/min/1.73 m(2)). Greater reductions in mean HbA1c level were
      observed with dapagliflozin (5 mg, -0.41%; 10 mg, -0.45%) than with placebo (
      0.06%) at week 24 and these were greater in patients with higher baseline HbA1c
      levels. Fasting plasma glucose (FPG) was also significantly reduced with
      dapagliflozin (5 mg, -8.6 mg/dl; 10 mg, -13.7 mg/dl) compared with placebo (+5.8
      mg/dl). Dapagliflozin significantly reduced body weight (5 mg, -2.13 kg; 10 mg, 
      2.22 kg) compared with placebo (-0.84 kg). Overall, 47.7 and 64.8% of patients
      with dapagliflozin 5 and 10 mg, respectively, and 51.7% with placebo experienced
      >= 1 adverse event, mostly mild or moderate, and unrelated to study treatment.
      Two patients on dapagliflozin 10 mg reported hypoglycaemia. Four patients across
      all groups reported events suggestive of genital infection and four of urinary
      tract infection. No events of pyelonephritis were reported. CONCLUSION:
      Dapagliflozin (5 and 10 mg) was well tolerated and effective in reducing HbA1c,
      FPG and body weight over 24 weeks in Japanese patients with T2DM inadequately
      controlled by diet and exercise.

PMID- 24909295
TI  - German medical students' interest in and knowledge about human sexuality in 1972
      and 2012.
AB  - INTRODUCTION: During the 1970s, a growing number of medical schools began to
      recognize the importance of medical education concerning human sexuality.
      Currently, most medical schools provide at least some instruction in human
      sexuality. AIM: In light of this development, the present study aimed to compare
      the interest in and knowledge about human sexuality of medical students from two
      different time periods. METHODS: The answers to a self-constructed questionnaire
      of 236 students in 1972 were compared with those of 259 students in 2012.
      Students were asked whether they were interested in education regarding human
      sexuality and which specific topics they felt should be included in the medical
      curriculum. The students' knowledge in the following domains was assessed: sexual
      development, sexual behavior, sexual physiology and psychology, and sexual
      medicine. MAIN OUTCOME MEASURES: The two cohorts were compared with regard to
      those specific sexuality-related topics in which the students were most and least
      interested in. Furthermore, the number of correct responses to the knowledge
      questions was compared. RESULTS: While in 1972, 99.2% of the students were
      interested in medical education about human sexuality, in 2012, 80.3% showed an
      interest. The connection of disorders from different medical disciplines with
      sexuality was rated as most interesting by both the students from 1972 and 2012.
      Medical students from 2012 gave 50.3% correct answers to the knowledge questions,
      whereas students from 1972 correctly answered 46.3% of the questions.
      CONCLUSIONS: Although interest in education concerning human sexuality has
      decreased, the majority of students view it as an important topic. Nevertheless,
      medical students still lack knowledge about important aspects of human sexuality
      (e.g., psychosexual development and relative safety of different contraceptives).
      Therefore, more time should be dedicated to education concerning human sexuality
      and its cultural, societal, and health aspects in particular.

PMID- 24909294
TI  - Pharmacological tools for hydrogen sulphide research: a brief, introductory guide
      for beginners.
AB  - The purpose of this brief review is to help researchers in their initial approach
      to the H2S field and to provide answers for the most frequently posed questions
      by newcomers to the topic related to H2S donors and inhibitors of H2S synthesis,
      as well as methods to measure H2S production. Here the reader will find a
      practical guide that provides fast and to the point information on how to (i)
      deliver H2S to cells; (ii) modulate its endogenous production; and (iii) measure
      its levels in fluids, cells and tissues in order to gain an understanding of its
      role in health and disease.

PMID- 24909296
TI  - Targeting SIM2-s decreases glioma cell invasion through mesenchymal--epithelial
      transition.
AB  - Glioma is a common primary intracranial carcinoma with high incidence,
      recurrence, and motility. Single minded homolog 2-short form (SIM2-s), a member
      of basic helix-loop-helix (bHLH) family, is reported to be expressed in glioma
      and might play a role in the invasion. In the present study, we investigated the
      importance of SIM2-s in glioma invasion and further explored the potential
      mechanisms. We showed that targeting SIM2-s by interference technology could
      decrease cell adhesion to fibronectin, induce cell aggregation and cytoskeletal
      changes. Furthermore, we showed that targeting SIM2-s increased the expression of
      epithelial markers and decreased the expression of mesenchymal markers, that is
      mesenchymal-epithelial transition (MET). Targeting SIM2-s decreased self-renewal
      of glioma stem cells by tumor sphere formation assay. Taken together, our results
      indicated that MET is involved in the inhibition of glioma invasion by targeting
      SIM2-s, and SIM2-s may be a new gene target.

PMID- 24909297
TI  - Should we recommend neuroaminidase inhibitors for influenza?

PMID- 24909298
TI  - Socio-environmental variables associated with malnutrition and intestinal
      parasitoses in the child population of Misiones, Argentina.
AB  - OBJECTIVES: The aim was to analyze the socio-environmental variables associated
      with malnutrition and intestinal parasitoses in children from Aristobulo del
      Valle, Province of Misiones (Argentina). METHODS: A cross-sectional study was
      performed in 2,291 schoolchildren (age, 4-14 years). Body weight and height were
      measured and body mass index was calculated. NHANES III reference was used to
      estimate the nutritional status-underweight, stunting, wasting, overweight, and
      obesity. The parasitological analysis was performed by fecal and anal brush
      samples. The socio-environmental variables were surveyed using a semi-structured
      questionnaire. These variables were processed by categorical principal component
      analysis (cat-PCA). RESULTS: The two first axes defined four subgroups of
      schoolchildren: three of these were associated with urban characteristics (high,
      middle, and periurban), whereas the remaining subgroup was considered rural.
      Stunting and parasitic infections occurred mainly in the periurban group, that is
      the group of higher socio-environmental vulnerability. On the other hand, the
      highest prevalence of overweight and obesity and the lowest parasitism was
      observed in the high urban group. CONCLUSIONS: The similarity between rural and
      middle urban groups in stunting prevalence reveals that cities are not healthier
      than rural environments. On the contrary, the fact that the rural group presents
      the lowest prevalence of overweight reaffirms that poverty and malnutrition are
      progressively moving from rural to urban areas, and that rural children have
      still more diverse and healthy diets favored by the consumption of homemade
      products (i.e., orchards, animal husbandry, etc.), placing them at an earlier
      stage of the nutrition transition.

PMID- 24909300
TI  - A brain-wide association study of DISC1 genetic variants reveals a relationship
      with the structure and functional connectivity of the precuneus in schizophrenia.
AB  - The Disrupted in Schizophrenia Gene 1 (DISC1) plays a role in both neural
      signaling and development and is associated with schizophrenia, although its
      links to altered brain structure and function in this disorder are not fully
      established. Here we have used structural and functional MRI to investigate links
      with six DISC1 single nucleotide polymorphisms (SNPs). We employed a brain-wide
      association analysis (BWAS) together with a Jacknife internal validation approach
      in 46 schizophrenia patients and 24 matched healthy control subjects. Results
      from structural MRI showed significant associations between all six DISC1
      variants and gray matter volume in the precuneus, post-central gyrus and middle
      cingulate gyrus. Associations with specific SNPs were found for rs2738880 in the
      left precuneus and right post-central gyrus, and rs1535530 in the right precuneus
      and middle cingulate gyrus. Using regions showing structural associations as
      seeds a resting-state functional connectivity analysis revealed significant
      associations between all 6 SNPS and connectivity between the right precuneus and
      inferior frontal gyrus. The connection between the right precuneus and inferior
      frontal gyrus was also specifically associated with rs821617. Importantly
      schizophrenia patients showed positive correlations between the six DISC-1 SNPs
      associated gray matter volume in the left precuneus and right post-central gyrus
      and negative symptom severity. No correlations with illness duration were found.
      Our results provide the first evidence suggesting a key role for structural and
      functional connectivity associations between DISC1 polymorphisms and the
      precuneus in schizophrenia.

PMID- 24909301
TI  - Damage of photoreceptor-derived cells in culture induced by light emitting diode
      derived blue light.
AB  - Our eyes are increasingly exposed to light from the emitting diode (LED) light of
      video display terminals (VDT) which contain much blue light. VDTs are equipped
      with televisions, personal computers, and smart phones. The present study aims to
      clarify the mechanism underlying blue LED light-induced photoreceptor cell
      damage. Murine cone photoreceptor-derived cells (661 W) were exposed to blue,
      white, or green LED light (0.38 mW/cm(2)). In the present study, blue LED light
      increased reactive oxygen species (ROS) production, altered the protein
      expression level, induced the aggregation of short-wavelength opsins (S-opsin),
      resulting in severe cell damage. While, blue LED light damaged the primary
      retinal cells and the damage was photoreceptor specific. N-Acetylcysteine (NAC),
      an antioxidant, protected against the cellular damage induced by blue LED light.
      Overall, the LED light induced cell damage was wavelength-, but not energy
      dependent and may cause more severe retinal photoreceptor cell damage than the
      other LED light.

PMID- 24909302
TI  - Identification of Coxiella burnetii surface-exposed and cell envelope associated
      proteins using a combined bioinformatics plus proteomics strategy.
AB  - The Gram-negative pathogen Coxiella burnetii is an intracellular bacterium that
      replicates within the phagolysosomal vacuoles of eukaryotic cells. This pathogen
      can infect a wide range of hosts, and is the causative agent of Q fever in
      humans. Surface-exposed and cell envelope associated proteins are thought to be
      important for both pathogenesis and protective immunity. Herein, we propose a
      complementary strategy consisting of (i) in silico prediction and (ii) inventory
      of the proteomic composition using three enrichment approaches coupled with
      protein identification. The efficiency of classical Triton X-114 phase
      partitioning was compared with two novel procedures; isolation of alkaline
      proteins by liquid-phase IEF, and cell surface enzymatic shaving using
      biofunctional magnetic beads. Of the 2026 protein sequences analyzed using seven
      distinct bioinformatic algorithms, 157 were predicted to be outer membrane
      proteins (OMP) and/or lipoproteins (LP). Using the three enrichment protocols, we
      identified 196 nonredundant proteins, including 39 predicted OMP and/or LP, 32
      unknown or poorly characterized proteins, and 17 effectors of the Type IV
      secretion system. We additionally identified eight proteins with moonlighting
      activities, and several proteins apparently peripherally associated with integral
      or anchored OMP and/or LP. 

PMID- 24909303
TI  - Comparison of early clinical outcomes between ABSORB bioresorbable vascular
      scaffold and everolimus-eluting stent implantation in a real-world population.
AB  - OBJECTIVES: To compare the early clinical outcomes between ABSORB bioresorbable
      vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA) and cobalt chromium
      everolimus-eluting stents in real-world patients with mostly complex disease.
      BACKGROUND: BVS represents the most interesting development in the drug-eluting
      stent field over recent years with promising results emerging from clinical
      trials. Available data however on the use of the ABSORB in real-world patients is
      limited. METHODS: All patients (n = 92) treated with BVS and 1296 patients
      treated with EES were included in this study. Propensity score matching was
      performed to adjust for differences in baseline clinical characteristics,
      yielding 92 patient pairs (BVS = 92 patients with 137 lesions and EES = 92
      patients with 124 lesions). Clinical outcomes were examined between the 2 groups
      at 6-months. RESULTS: In both groups, most lesions were classified as either B2
      or C (83.9% vs. 77.4%, P = 0.19). Predilatation (97.8% vs. 75.8%, P < 0.01) as
      well as postdilation (99.3% vs. 77.4%, P < 0.01) was more common in the BVS
      group. Clinical outcomes at 6-months were similar between the two groups with
      respect to both target lesion revascularization (3.3% vs. 5.4%, P = 0.41) and
      major adverse cardiac events (defined as the composite of target vessel
      revascularization, follow-up myocardial infraction and all-cause death) (3.3% vs.
      7.6%, P = 0.19). CONCLUSIONS: ABSORB BVS for the treatment of complex lesions
      appears to be associated with good procedural and early clinical outcomes similar
      to those observed with conventional drug-eluting stents. Larger studies with long
      term follow-up are required in order to fully assess the role of BVS in the
      treatment of such lesions and how this compares with that of conventional stents.
      (c) 2014 Wiley Periodicals, Inc.

PMID- 24909304
TI  - Inhaled corticosteroids and systemic inflammatory response in community-acquired
      pneumonia: a prospective clinical study.
AB  - BACKGROUND AND OBJECTIVE: The previous use of inhaled corticosteroids (ICS) may
      reduce the inflammatory response and mortality in patients with community
      acquired pneumonia (CAP). METHODS: We measured serum levels of several
      inflammatory biomarkers, as well as mortality at various time-points, in 663
      consecutive patients hospitalized for CAP; 128 (19%) were receiving chronic
      outpatient treatment with ICS. Patients on previous oral corticosteroids were
      excluded from the analysis. RESULTS: On admission, patients treated with ICS were
      older; had been diagnosed with chronic obstructive pulmonary disease (COPD),
      asthma and pneumonia in the previous year more often; and had higher CAP severity
      risk classes and lower tumour necrosis factor (TNF)-alpha (P < 0.001) and
      interleukin (IL)-6 (P = 0.015) serum levels. After adjusting for potential
      confounders, this association persisted for TNF-alpha (P < 0.001), but not for IL
      6. Mortality at 30 and 90 days tended to be lower in patients treated with ICS (P
      = 0.062 and 0.050, respectively), but mortality was similar after 1 year in both
      groups (16, 13% vs 81, 15% for patients treated and not treated with ICS,
      respectively). Hospital readmission rate after 1 year was higher in patients
      treated with ICS (49, 38% vs 109, 20%, P < 0.001). The association of ICS
      treatment with a previous diagnosis of pneumonia, lower levels of TNF-alpha and
      IL-6 on admission and higher readmission rates during follow up persisted in the
      subpopulation of 210 patients with COPD. CONCLUSIONS: Previous use of ICS in
      patients hospitalized for CAP is associated with a reduced systemic inflammatory
      response without any impact on long-term mortality.

PMID- 24909305
TI  - Self-propelled polymer multilayer Janus capsules for effective drug delivery and
      light-triggered release.
AB  - We present herein a novel hybrid, polymer-based motor that was fabricated by the
      template-assisted polyelectrolyte layer-by-layer (LbL) deposition of a thin gold
      layer on one side, followed by chemical immobilization of a catalytic enzyme.
      Such Janus capsule motors can self-propel at 0.1% peroxide fuel concentration at
      physiological temperature and have a higher speed as compared to Pt-based
      synthetic motors. They were exploited for encapsulation of the chemotherapeutic
      anticancer drug, doxorubicin, for navigation to target a cell layer by an
      external magnetic field, and for triggered drug release activated by NIR light.
      This work provides high potential in the development of multifunctional polymer
      based engines for biomedical applications such as targeted drug delivery. 

PMID- 24909306
TI  - Loss of Tau results in defects in photoreceptor development and progressive
      neuronal degeneration in Drosophila.
AB  - Accumulations of Tau, a microtubule-associated protein (MAP), into
      neurofibrillary tangles is a hallmark of Alzheimer's disease and other
      tauopathies. However, the mechanisms leading to this pathology are still unclear:
      the aggregates themselves could be toxic or the sequestration of Tau into tangles
      might prevent Tau from fulfilling its normal functions, thereby inducing a loss
      of function defect. Surprisingly, the consequences of losing normal Tau
      expression in vivo are still not well understood, in part due to the fact that
      Tau knockout mice show only subtle phenotypes, presumably due to the fact that
      mammals express several MAPs with partially overlapping functions. In contrast,
      flies express fewer MAP, with Tau being the only member of the Tau/MAP2/MAP4
      family. Therefore, we used Drosophila to address the physiological consequences
      caused by the loss of Tau. Reducing the levels of fly Tau (dTau) ubiquitously
      resulted in developmental lethality, whereas deleting Tau specifically in neurons
      or the eye caused progressive neurodegeneration. Similarly, chromosomal mutations
      affecting dTau also caused progressive degeneration in both the eye and brain.
      Although photoreceptor cells initially developed normally in dTau knockdown
      animals, they subsequently degenerated during late pupal stages whereas weaker
      dTau alleles caused an age-dependent defect in rhabdomere structure. Expression
      of wild type human Tau partially rescued the neurodegenerative phenotype caused
      by the loss of endogenous dTau, suggesting that the functions of Tau proteins are
      functionally conserved from flies to humans.

PMID- 24909308
TI  - MicroRNA-based biotechnology for plant improvement.
AB  - MicroRNAs (miRNAs) are an extensive class of newly discovered endogenous small
      RNAs, which negatively regulate gene expression at the post-transcription levels.
      As the application of next-generation deep sequencing and advanced
      bioinformatics, the miRNA-related study has been expended to non-model plant
      species and the number of identified miRNAs has dramatically increased in the
      past years. miRNAs play a critical role in almost all biological and metabolic
      processes, and provide a unique strategy for plant improvement. Here, we first
      briefly review the discovery, history, and biogenesis of miRNAs, then focus more
      on the application of miRNAs on plant breeding and the future directions.
      Increased plant biomass through controlling plant development and phase change
      has been one achievement for miRNA-based biotechnology; plant tolerance to
      abiotic and biotic stress was also significantly enhanced by regulating the
      expression of an individual miRNA. Both endogenous and artificial miRNAs may
      serve as important tools for plant improvement.

PMID- 24909309
TI  - A novel pH-responsive interpolyelectrolyte hydrogel complex for the oral delivery
      of levodopa. Part II: characterization and formulation of an IPEC-based tablet
      matrix.
AB  - This study was undertaken in order to apply a synthesized interpolyelectrolyte
      complex (IPEC) of polymethacrylate and carboxymethylcellulose as a controlled
      release oral tablet matrix for the delivery of the model neuroactive drug
      levodopa. The IPEC (synthesized in Part I of this work) was characterized by
      techniques such as Fourier Transform Infra-Red (FTIR) spectroscopy, Differential
      Scanning Calorimetry (DSC), Advanced DSC (ADSC), and Scanning Electron Microscopy
      (SEM). The tablet matrices were formulated and characterized for their drug
      delivery properties and in vitro drug release. FTIR confirmed the interaction
      between the two polymers. The IPEC composite generated tablet matrices with a
      hardness ranging from 19.152-27.590 N/mm and a matrix resilience ranging between
      42 and 46%. An IPEC of polymethacrylate and carboxymethylcellulose was indeed an
      improvement on the inherent properties of the native polymers providing a
      biomaterial with the ability to release poorly soluble drugs such as levodopa at
      a constant rate over a prolonged period of time.

PMID- 24909307
TI  - Molecular targeting of TRF2 suppresses the growth and tumorigenesis of
      glioblastoma stem cells.
AB  - Glioblastoma is the most prevalent primary brain tumor and is essentially
      universally fatal within 2 years of diagnosis. Glioblastomas contain cellular
      hierarchies with self-renewing glioblastoma stem cells (GSCs) that are often
      resistant to chemotherapy and radiation therapy. GSCs express high amounts of
      repressor element 1 silencing transcription factor (REST), which may contribute
      to their resistance to standard therapies. Telomere repeat-binding factor 2
      (TRF2) stablizes telomeres and REST to maintain self-renewal of neural stem cells
      and tumor cells. Here we show viral vector-mediated delivery of shRNAs targeting
      TRF2 mRNA depletes TRF2 and REST from GSCs isolated from patient specimens. As a
      result, GSC proliferation is reduced and the level of proteins normally expressed
      by postmitotic neurons (L1CAM and beta3-tubulin) is increased, suggesting that
      loss of TRF2 engages a cell differentiation program in the GSCs. Depletion of
      TRF2 also sensitizes GSCs to temozolomide, a DNA-alkylating agent currently used
      to treat glioblastoma. Targeting TRF2 significantly increased the survival of
      mice bearing GSC xenografts. These findings reveal a role for TRF2 in the
      maintenance of REST-associated proliferation and chemotherapy resistance of GSCs,
      suggesting that TRF2 is a potential therapeutic target for glioblastoma.

PMID- 24909310
TI  - Primary Sjogren's syndrome is characterized by distinct phenotypic and
      transcriptional profiles of IgD+ unswitched memory B cells.
AB  - OBJECTIVE: The significance of distinct B cell abnormalities in primary Sjogren's
      syndrome (SS) remains to be established. We undertook this study to analyze the
      phenotype and messenger RNA (mRNA) transcript profiles of B cell subsets in
      patients with primary SS and to compare them with those in sicca syndrome
      patients and healthy controls. METHODS: CD19+ B cells from 26 patients with
      primary SS, 27 sicca syndrome patients, and 22 healthy controls were analyzed by
      flow cytometry. Gene expression profiles of purified B cell subsets (from 3-5
      subjects per group per test) were analyzed using Affymetrix gene arrays. RESULTS:
      Patients with primary SS had lower frequencies of CD27+IgD- switched memory B
      cells and CD27+IgD+ unswitched memory B cells compared with healthy controls.
      Unswitched memory B cell frequencies were also lower in sicca syndrome patients
      and correlated inversely with serologic hyperactivity in both disease states.
      Further, unswitched memory B cells in primary SS had lower expression of CD1c and
      CD21. Gene expression analysis of CD27+ memory B cells separated patients with
      primary SS from healthy controls and identified a subgroup of sicca syndrome
      patients with a primary SS-like transcript profile. Moreover, unswitched memory B
      cell gene expression analysis identified 187 genes differentially expressed
      between patients with primary SS and healthy controls. CONCLUSION: A decrease in
      unswitched memory B cells with serologic hyperactivity is characteristic of both
      established primary SS and a subgroup of sicca syndrome, which suggests the value
      of these B cells both as biomarkers of future disease progression and for
      understanding disease pathogenesis. Overall, the mRNA transcript analysis of
      unswitched memory B cells suggests that their activation in primary SS takes
      place through innate immune pathways in the context of attenuated antigen
      mediated adaptive signaling. Thus, our findings provide important insight into
      the mechanisms and potential consequences of decreased unswitched memory B cells
      in primary SS.

PMID- 24909311
TI  - A systematic review of bevacizumab efficacy in breast cancer.
AB  - Angiogenesis is a key component of cancer growth, invasion and metastasis.
      Therefore, inhibition of angiogenesis is an attractive strategy for the treatment
      of cancer. We systematically describe phase II and III clinical trials of
      bevacizumab for the treatment of breast cancer. METHODS: A computer-based
      literature search was carried out using PUBMED and conference databases. Original
      phase II and III studies reporting >=15 patients who received bevacizumab were
      included. RESULTS: 41 phase II trials were identified in the metastatic setting.
      Most trials found bevacizumab treatment feasible. Response rates (RR) varied from
      0% to 76.5%, time to progression (TTP)/progression free survival (PFS) from 2.4
      to 25.3 months and overall survival from 11.5 to more than 38 months. 14 phase
      III trials including more than 4400 patients with MBC unanimously showed
      increased RR and PFS, however, no trials demonstrated an OS benefit. In the
      neoadjuvant setting 23 phase II and III trials were identified. All studies found
      increased pCR/tpCR but no benefit in terms of OS could be demonstrated. The only
      study conducted in the adjuvant setting failed to show any survival benefit of
      bevacizumab. CONCLUSION: Despite increased response rates in both the metastatic
      and neoadjuvant setting, bevacizumab has failed to show any OS benefit. Future
      trials should include identification of robust predictive biomarkers in order to
      improve our understanding of molecular biomarkers and mechanisms.

PMID- 24909312
TI  - Systemic treatments for brain metastases from breast cancer, non-small cell lung
      cancer, melanoma and renal cell carcinoma: an overview of the literature.
AB  - The frequency of metastatic brain tumors has increased over recent years; the
      primary tumors most involved are breast cancer, lung cancer, melanoma and renal
      cell carcinoma. While radiation therapy and surgery remain the mainstay treatment
      in selected patients, new molecular drugs have been developed for brain
      metastases. Studies so far report interesting results. This review focuses on
      systemic cytotoxic drugs and, in particular, on new targeted therapies and their
      clinically relevant activities in brain metastases from solid tumors in adults. 

PMID- 24909313
TI  - Molecular weight between entanglements for kappa- and iota-carrageenans in an
      ionic liquid.
AB  - The molecular weight between entanglements (Me) for kappa- and iota-carrageenans,
      sulfated galactans, was examined in concentrated solutions using an ionic liquid
      1-butyl-3-methylimidazolium acetate as a solvent. The dynamic viscoelasticity
      data for the solutions measured at different temperatures were overlapped
      according to the time-temperature superposition principle, and the obtained
      master curves exhibited the flow and rubbery plateau zones, being typical of
      concentrated polymer solutions having entanglement coupling. The values of Me for
      kappa- and iota-carrageenans in the solutions were determined from the plateau
      moduli. Then the values of Me in the molten state (Me,melt) estimated as a
      material constant to be 6.6*10(3) and 7.2*10(3), respectively. The close values
      of Me,melt for kappa- and iota-carrageenans indicate that 4-sulfate group of iota
      carrageenan are not so influential for the entanglement network. Compared with
      agarose, a non-sulfate galactan, carrageenans have larger values of average
      spacing between entanglements. 

PMID- 24909314
TI  - Maltodextrin based proniosomes of nateglinide: bioavailability assessment.
AB  - The present study delineates the fabrication of maltodextrin based proniosomes of
      nateglinide and their potential as controlled delivery system for diabetic
      therapy. New Zealand albino male rabbits have been used as animal model for in
      vivo study. To evaluate the bioavailability of nateglinide proniosome, a rapid,
      simple and sensitive HPLC method with photodiode array detection was developed
      and validated to determine nateglinide in rabbit plasma. Chromatographic
      separation was achieved by a reverse phase C18 column using a mixture of
      acetonitrile:methanol:10mM phosphate buffer (pH 3.5) in the ratio of 56:14:30
      (%v/v) as the mobile phase at a flow rate of 1.0ml/min and quantified based on
      drug/IS peak area ratios. Gliclazide was used as the internal standard. The intra
      and inter-day relative standard deviations of four tested concentrations were
      below 2%. The nateglinide proniosome formulation exhibited significantly higher
      plasma concentration than those of pure drug. The study revealed that the rate
      and extent of absorption of nateglinide from the proniosomal formulation was
      comparatively enhanced that of pure drug. Maltodextrin based proniosomes of
      nateglinide is not only simple and cost efficient delivery but also offers a
      useful and promising carrier for diabetic therapy through oral administration. 

PMID- 24909315
TI  - Response to "No evidence of neuroprotection? Perhaps not...perhaps so".

PMID- 24909316
TI  - Ab initio theoretical investigation of beryllium and beryllium hydride
      nanoparticles and nanocrystals with implications for the corresponding infinite
      systems.
AB  - With the initial motivation of optimizing hydrogen storage in beryllium
      nanocrystals, we have thoroughly and systematically studied the structural,
      cohesive, and electronic properties of Ben and BenHxn (n = 2-160, x = 0.1-2.4)
      nanoparticles as a function of both size (n) and hydrogen content (x), using
      density functional theory with a properly selected meta-hybrid functional and
      high level coupled cluster CCSD(T) theory for comparison. We have calculated the
      binding energies of Ben, BenHxn and [BeH2]n nanoparticles for a large range of n
      values. In the limit n->infinity, we have obtained the experimental binding
      energy of a Be crystal (3.32 eV) with unexpectedly very good agreement (3.26 +/-
      0.06 eV), and a predicted value of 7.85 eV +/- 0.02 eV for the binding energy of
      the [BeH2]infinity infinite system. We also predict that the majority of the
      lowest energy stoichiometric BenH2n nanoparticles are chains or chain-like
      structures. The tendency towards chain stabilization of BenHxn nanoparticles
      increases, as x approaches the stoichiometric value x = 2, leading for large
      values of n, as n->infinity, to polymeric forms of bulk BeH2, which in the past
      have been considered as the leading forms of solid BeH2. For such 1-dimensional
      forms of [BeH2]n we have obtained and verified that the binding energy varies
      exactly proportionally to n(-1). The extrapolated desorption energy for such
      polymeric forms of solid BeH2 is found to be 19 +/- 3 kJ mol(-1) in juxtaposition
      to the experimental value of 19 kJ mol(-1) for solid BeH2, suggesting that the
      difference DeltaE in cohesive energy between the orthorhombic and polymeric form
      is very small (DeltaE~ 3 kJ mol(-1)). This is in full accord with the early
      discrepancies in the literature in determining and distinguishing the real
      crystal structure of solid BeH2. 

PMID- 24909317
TI  - Sensitizer design for efficient triplet-triplet annihilation upconversion:
      annihilator-appended tris-cyclometalated Ir(III) complexes.
AB  - Enhanced triplet-triplet annihilation upconversion efficiency is achieved with
      two tris-cyclometalated iridium sensitizers covalently tethered with a pyrene
      annihilator. The improved sensitizing ability and very long phosphorescence
      lifetimes (1-2 ms) of these bichromophore molecules are both attributed to the
      intramolecular energy transfer between the iridium complex and appended pyrene
      group. 

PMID- 24909318
TI  - Effects of laser treatment on the expression of cytosolic proteins in the
      synovium of patients with osteoarthritis.
AB  - BACKGROUND AND OBJECTIVE: Low level laser therapy (LLLT) has been developed for
      non-invasive treatment of joint diseases. We have previously shown that LLLT
      influenced synovial protein expression in rheumatoid arthritis (RA). The aim of
      this study was to assess the effects of laser irradiation on osteoarthritic (OA)
      synovial protein expression. STUDY DESIGN/MATERIALS AND METHODS: The synovial
      membrane samples removed from the knees of 6 OA patients were irradiated ex vivo
      using near infrared diode laser (807-811 nm; 25 J/cm(2) ). An untreated sample
      taken from the same patient served as control. Synovial protein separation and
      identification were performed by two-dimensional differential gel electrophoresis
      and mass spectrometry, respectively. RESULTS: Eleven proteins showing altered
      expression due to laser irradiation were identified. There were three patients
      whose tissue samples demonstrated a significant increase (P < 0.05) in
      mitochondrial heat shock 60 kD protein 1 variant 1. The expression of the other
      proteins (calpain small subunit 1, tubulin alpha-1C and beta 2, vimentin variant
      3, annexin A1, annexin A5, cofilin 1, transgelin, and collagen type VI alpha 2
      chain precursor) significantly decreased (P < 0.05) compared to the control
      samples. CONCLUSIONS: A single diode laser irradiation of the synovial samples of
      patients with osteoarthritis can statistically significantly alter the expression
      of some proteins in vitro. These findings provide some more evidence for
      biological efficacy of LLLT treatment, used for osteoarthritis.

PMID- 24909319
TI  - Multiple system atrophy: prognostic indicators of survival.
AB  - Neurological and autonomic presentation in multiple system atrophy (MSA) may
      predict early mortality. Quantification of early autonomic failure as a mortality
      predictor is lacking. Early neurological and autonomic clinical features were
      retrospectively reviewed in 49 MSA cases (median age at onset, 56.1 years; 16
      women) confirmed by autopsy at Mayo Clinic. When available, the 10-point
      composite autonomic severity score derived from the autonomic reflex screen
      provided quantification of the degree of autonomic failure and thermoregulatory
      sweat test quantitated body surface anhidrosis. Symptoms at onset were autonomic
      in 50%, parkinsonian in 30%, and cerebellar in 20% of cases. Survival (median
      [95% confidence interval]) was 8.6 [6.7-10.2] years. Survival was shorter in
      patients with early laboratory evidence of generalized (composite autonomic
      severity score >= 6) autonomic failure (7.0 [3.9-9.8] vs. 9.8 [4.6-13.8] years; P
      = 0.036), and early requirement of bladder catheterization (7.3 [3.1-10.2] vs.
      13.7 [8.5-14.9] years; P = 0.003) compared with those without these clinical
      features. On Cox proportional analysis, prognostic indicators of shorter survival
      were older age at onset (hazard ratio [95% confidence interval], 1.04 [1.01
      1.08]; P = 0.03), early requirement of bladder catheterization (7.9 [1.88-38.63];
      P = 0.004), and early generalized (composite autonomic severity score >= 6)
      autonomic failure (2.8 [1.01-9.26]; P = 0.047). Gender, phenotype, and early
      development of gait instability, aid-requiring ambulation, orthostatic symptoms,
      neurogenic bladder, or significant anhidrosis (thermoregulatory sweat test >=
      40%) were not indicators of shorter survival. Our data suggest that early
      development of severe generalized autonomic failure more than triples the risk of
      shorter survival in patients with MSA.

PMID- 24909320
TI  - A diagnostic approach for defining idiopathic remitting diabetes: a retrospective
      cohort study.
AB  - BACKGROUND: 11 patients were referred to our Molecular Genetics Department at the
      Royal Devon and Exeter Hospital between 2000-2012 with a physician's diagnosis of
      remitting diabetes. Our aim was to identify patients with remitting diabetes
      whose clinical presentation is not explained by any known aetiology of diabetes.
      METHODS: We obtained longitudinal clinical data on all 11 patients from the
      hospital records. All patients were aged between 0.5 and 35 years at diagnosis.
      We applied clinical criteria derived from the literature to establish 1) definite
      diabetes, 2) diabetes initially severe-requiring treatment with insulin, 3)
      remission of diabetes, and 4) exclusion of known causes of remitting diabetes.
      RESULTS: 10 out of 11 patients had an alternative explanation for their remission
      or a clear diagnosis was not identified. We identified a single patient with
      idiopathic remitting diabetes using these criteria. The patient was a white
      Caucasian female diagnosed aged 15 with symptoms of diabetes, laboratory glucose
      of 21.2 mmol/L and HbA1c 134 mmol/mol. Her BMI was 23.6 kg/m2. She was treated
      with basal bolus insulin but discontinued two years after diagnosis due to
      hypoglycaemia. 13 years post diagnosis, she had a normal oral glucose tolerance
      test during pregnancy (fasting glucose 4.5 mmol/L, 2 hr glucose 4.8 mmol/L) and
      an HbA1c of 30 mmol/mol. This patient does not appear to have Type 1 or Type 2
      diabetes, and furthermore does not fit into current classifications of diabetes.
      CONCLUSIONS: Idiopathic remitting diabetes is rare but does exist. Strict
      clinical criteria are important to ensure patients have a robust clinical
      diagnosis. Identification of more patients with idiopathic remitting diabetes
      will enable further study of the clinical course of this syndrome. Applying these
      strict criteria will allow the identification of patients with remitting diabetes
      to assess its aetiology.

PMID- 24909321
TI  - Bumblebees learn polarization patterns.
AB  - Foraging insect pollinators such as bees must find and identify flowers in a
      complex visual environment. Bees use skylight polarization patterns for
      navigation, a capacity mediated by the polarization-sensitive dorsal rim area
      (DRA) of their eye. While other insects use polarization sensitivity to identify
      appropriate habitats, oviposition sites, and food sources, to date no
      nonnavigational functions of polarization vision have been identified in bees.
      Here we investigated the ability of bumblebees (Bombus terrestris) to learn
      polarization patterns on artificial "flowers" in order to obtain a food reward.
      We show that foraging bumblebees can learn to discriminate between two
      differently polarized targets, but only when the target artificial "flower" is
      viewed from below. A context for these results is provided by polarization
      imaging of bee-pollinated flowers, revealing the potential for polarization
      patterns in real flowers. Bees may therefore have the ability to use polarization
      vision, possibly mediated by their polarization-sensitive DRA, both for
      navigation and to learn polarization patterns on flowers, the latter being the
      first nonnavigational function for bee polarization vision to be identified.

PMID- 24909322
TI  - An Arp2/3 nucleated F-actin shell fragments nuclear membranes at nuclear envelope
      breakdown in starfish oocytes.
AB  - Animal cells disassemble and reassemble their nuclear envelopes (NEs) upon each
      division. Nuclear envelope breakdown (NEBD) serves as a major regulatory
      mechanism by which mixing of cytoplasmic and nuclear compartments drives the
      complete reorganization of cellular architecture, committing the cell for
      division. Breakdown is initiated by phosphorylation-driven partial disassembly of
      the nuclear pore complexes (NPCs), increasing their permeability but leaving the
      overall NE structure intact. Subsequently, the NE is rapidly broken into membrane
      fragments, defining the transition from prophase to prometaphase and resulting in
      complete mixing of cyto- and nucleoplasm. However, the mechanism underlying this
      rapid NE fragmentation remains largely unknown. Here, we show that NE
      fragmentation during NEBD in starfish oocytes is driven by an Arp2/3 complex
      nucleated F-actin "shell" that transiently polymerizes on the inner surface of
      the NE. Blocking the formation of this F-actin shell prevents membrane
      fragmentation and delays entry of large cytoplasmic molecules into the nucleus.
      We observe spike-like protrusions extending from the F-actin shell that appear to
      "pierce" the NE during the fragmentation process. Finally, we show that NE
      fragmentation is essential for successful reproduction, because blocking this
      process in meiosis leads to formation of aneuploid eggs.

PMID- 24909323
TI  - Regulation of cyclin-substrate docking by a G1 arrest signaling pathway and the
      Cdk inhibitor Far1.
AB  - Eukaryotic cell division is often regulated by extracellular signals. In budding
      yeast, signaling from mating pheromones arrests the cell cycle in G1 phase. This
      arrest requires the protein Far1, which is thought to antagonize the G1/S
      transition by acting as a Cdk inhibitor (CKI), although the mechanisms remain
      unresolved. Recent studies found that G1/S cyclins (Cln1 and Cln2) recognize Cdk
      substrates via specific docking motifs, which promote substrate phosphorylation
      in vivo. Here, we show that these docking interactions are inhibited by pheromone
      signaling and that this inhibition requires Far1. Moreover, Far1 mutants that
      cannot inhibit docking are defective at cell-cycle arrest. Consistent with this
      arrest function, Far1 outcompetes substrates for association with G1/S cyclins in
      vivo, and it is present in large excess over G1/S cyclins during the
      precommitment period where pheromone can impose G1 arrest. Finally, a comparison
      of substrates that do and do not require docking suggests that Far1 acts as a
      multimode inhibitor that antagonizes both kinase activity and substrate
      recognition by Cln1/2-Cdk complexes. Our findings uncover a novel mechanism of
      Cdk regulation by external signals and shed new light on Far1 function to provide
      a revised view of cell-cycle arrest in this model system.

PMID- 24909324
TI  - Zelda potentiates morphogen activity by increasing chromatin accessibility.
AB  - Zygotic genome activation (ZGA) is a major genome programming event whereby the
      cells of the embryo begin to adopt specified fates. Experiments in Drosophila and
      zebrafish have revealed that ZGA depends on transcription factors that provide
      large-scale control of gene expression by direct and specific binding to gene
      regulatory sequences. Zelda (Zld) plays such a role in the Drosophila embryo,
      where it has been shown to control the action of patterning signals; however, the
      mechanisms underlying this effect remain largely unclear. A recent model proposed
      that Zld binding sites act as quantitative regulators of the spatiotemporal
      expression of genes activated by Dorsal (Dl), the morphogen that patterns the
      dorsoventral axis. Here we tested this model experimentally, using enhancers of
      brinker (brk) and short gastrulation (sog), both of which are directly activated
      by Dl, but at different concentration thresholds. In agreement with the model, we
      show that there is a clear positive correlation between the number of Zld binding
      sites and the spatial domain of enhancer activity. Likewise, the timing of
      expression could be advanced or delayed. We present evidence that Zld facilitates
      binding of Dl to regulatory DNA, and that this is associated with increased
      chromatin accessibility. Importantly, the change in chromatin accessibility is
      strongly correlated with the change in Zld binding, but not Dl. We propose that
      the ability of genome activators to facilitate readout of transcriptional input
      is key to widespread transcriptional induction during ZGA.

PMID- 24909325
TI  - Sexually dimorphic tridimensionally preserved pterosaurs and their eggs from
      China.
AB  - BACKGROUND: The pterosaur record is generally poor, with little information about
      their populations, and pterosaur eggs are even rarer, with only four isolated and
      flattened eggs found to date. RESULTS: We report here a population of a new
      sexually dimorphic pterosaur species (Hamipterus tianshanensis gen. et sp. nov.),
      with five exceptionally well-preserved three-dimensional eggs, from the Early
      Cretaceous deposit in northwestern China. About 40 male and female individuals in
      total were recovered, but the actual number associated might be in the hundreds.
      All of the discovered skulls have crests, which exhibit two different
      morphologies in size, shape, and robustness. The eggs show pliable depressions
      with cracking and crazing on the outer surface. The eggshell, observed by
      scanning electron microscopy and energy-dispersive spectroscopy, comprises a thin
      calcareous external hard shell followed by a soft membrane. CONCLUSIONS: These
      fossils shed new light on the reproductive strategy, ontogeny, and behavior of
      pterosaurs. The cranial crests show sexually dimorphic morphologies, with
      presumed males and females differing in crest size, shape, and robustness.
      Ontogenetic variation is reflected mainly in the expansion of the rostrum. The
      eggs have some external rigidity of the general pliable eggshell, and the
      microstructure of the eggshell is similar to that of some modern "soft" snake
      eggs. We suggest that this new pterosaur nested in colonies and thus exhibited
      gregarious behavior, a possible general trend for at least derived pterodactyloid
      pterosaurs.

PMID- 24909326
TI  - On the origin of a novel parasitic-feeding mode within suspension-feeding
      barnacles.
AB  - In his monograph on Cirripedia from 1851, Darwin pointed to a highly unusual,
      plateless, and most likely parasitic barnacle of uncertain phylogenetic affinity.
      Darwin's barnacle was Anelasma squalicola, found on deep-water sharks of the
      family Etmopteridae, or lantern sharks. The barnacle is uncommon and is therefore
      rarely studied. Recent observations by us have shown that they occur at an
      unusually high prevalence on the velvet belly lantern shark, Etmopterus spinax,
      in restricted fjord areas of western Norway. A phylogenetic analysis based on
      ribosomal DNA data (16S, 18S, and 28S) from 99 selected barnacle species,
      including all available pedunculate barnacle sequences from GenBank, shows that
      A. squalicola is most closely related (sister taxon) to the pedunculate barnacle
      Capitulum mitella. Both C. mitella and species of Pollicipes, situated one node
      higher in the tree, are conventional suspension feeders from the rocky
      intertidal. Our phylogenetic analysis now makes it possible to establish
      morphological homologies between A. squalicola and its sister taxon and provides
      the evolutionary framework to explain the unprecedented transition from a filter
      feeding barnacle to a parasitic mode of life.

PMID- 24909327
TI  - Dynamic assembly of a membrane signaling complex enables selective activation of
      NFAT by Orai1.
AB  - NFAT-dependent gene expression is essential for the development and function of
      the nervous, immune, and cardiovascular systems and kidney, bone, and skeletal
      muscle. Most NFAT protein resides in the cytoplasm because of extensive
      phosphorylation, which masks a nuclear localization sequence. Dephosphorylation
      by the Ca(2+)-calmodulin-activated protein phosphatase calcineurin triggers NFAT
      migration into the nucleus. In some cell types, NFAT can be activated by Ca(2+)
      nanodomains near open store-operated Orai1 and voltage-gated Ca(2+) channels in
      the plasma membrane. How local Ca(2+) near Orai1 is detected and whether other
      Orai channels utilize a similar mechanism remain unclear. Here, we report that
      the paralog Orai3 fails to activate NFAT. Orai1 is effective in activating gene
      expression via Ca(2+) nanodomains because it participates in a membrane-delimited
      signaling complex that forms after store depletion and brings calcineurin, via
      the scaffolding protein AKAP79, to calmodulin tethered to Orai1. By contrast,
      Orai3 interacts less well with AKAP79 after store depletion, rendering it
      ineffective in activating NFAT. A channel chimera of Orai3 with the N terminus of
      Orai1 was able to couple local Ca(2+) entry to NFAT activation, identifying the N
      terminal domain of Orai1 as central to Ca(2+) nanodomain-transcription coupling.
      The formation of a store-dependent signaling complex at the plasma membrane
      provides for selective activation of a fundamental downstream response by Orai1.

PMID- 24909328
TI  - The hippocampus and entorhinal cortex encode the path and Euclidean distances to
      goals during navigation.
AB  - BACKGROUND: Despite decades of research on spatial memory, we know surprisingly
      little about how the brain guides navigation to goals. While some models argue
      that vectors are represented for navigational guidance, other models postulate
      that the future path is computed. Although the hippocampal formation has been
      implicated in processing spatial goal information, it remains unclear whether
      this region processes path- or vector-related information. RESULTS: We report
      neuroimaging data collected from subjects navigating London's Soho district;
      these data reveal that both the path distance and the Euclidean distance to the
      goal are encoded by the medial temporal lobe during navigation. While activity in
      the posterior hippocampus was sensitive to the distance along the path, activity
      in the entorhinal cortex was correlated with the Euclidean distance component of
      a vector to the goal. During travel periods, posterior hippocampal activity
      increased as the path to the goal became longer, but at decision points, activity
      in this region increased as the path to the goal became closer and more direct.
      Importantly, sensitivity to the distance was abolished in these brain areas when
      travel was guided by external cues. CONCLUSIONS: The results indicate that the
      hippocampal formation contains representations of both the Euclidean distance and
      the path distance to goals during navigation. These findings argue that the
      hippocampal formation houses a flexible guidance system that changes how it
      represents distance to the goal depending on the fluctuating demands of
      navigation.

PMID- 24909329
TI  - The plant cytoskeleton, NET3C, and VAP27 mediate the link between the plasma
      membrane and endoplasmic reticulum.
AB  - The cortical endoplasmic reticulum (ER) network in plants is a highly dynamic
      structure, and it contacts the plasma membrane (PM) at ER-PM anchor/contact
      sites. These sites are known to be essential for communication between the ER and
      PM for lipid transport, calcium influx, and ER morphology in mammalian and fungal
      cells. The nature of these contact sites is unknown in plants, and here, we have
      identified a complex that forms this bridge. This complex includes (1) NET3C,
      which belongs to a plant-specific superfamily (NET) of actin-binding proteins,
      (2) VAP27, a plant homolog of the yeast Scs2 ER-PM contact site protein, and (3)
      the actin and microtubule networks. We demonstrate that NET3C and VAP27 localize
      to puncta at the PM and that NET3C and VAP27 form homodimers/oligomers and
      together form complexes with actin and microtubules. We show that F-actin
      modulates the turnover of NET3C at these puncta and microtubules regulate the
      exchange of VAP27 at the same sites. Based on these data, we propose a model for
      the structure of the plant ER-PM contact sites.

PMID- 24909330
TI  - From in vitro to in cellulo: structure-activity relationship of (2
      nitrophenyl)methanol derivatives as inhibitors of PqsD in Pseudomonas aeruginosa.
AB  - Recent studies have shown that compounds based on a (2-nitrophenyl)methanol
      scaffold are promising inhibitors of PqsD, a key enzyme of signal molecule
      biosynthesis in the cell-to-cell communication of Pseudomonas aeruginosa. The
      most promising molecule displayed anti-biofilm activity and a tight-binding mode
      of action. Herein, we report on the convenient synthesis and biochemical
      evaluation of a comprehensive series of (2-nitrophenyl)methanol derivatives. The
      in vitro potency of these inhibitors against recombinant PqsD as well as the
      effect of selected compounds on the production of the signal molecules HHQ and
      PQS in P. aeruginosa were examined. The gathered data allowed the establishment
      of a structure-activity relationship, which was used to design fluorescent
      inhibitors, and finally, led to the discovery of (2-nitrophenyl)methanol
      derivatives with improved in cellulo efficacy providing new perspectives towards
      the application of PqsD inhibitors as anti-infectives. 

PMID- 24909331
TI  - Immune responses of a chimaeric protein vaccine containing Mycoplasma
      hyopneumoniae antigens and LTB against experimental M. hyopneumoniae infection in
      pigs.
AB  - A recombinant chimaeric protein containing three Mycoplasma hyopneumoniae
      antigens (C-terminal portion of P97, heat shock protein P42, and NrdF) fused to
      an adjuvant, the B subunit of heat-labile enterotoxin of Escherichia coli (LTB),
      was used to immunize pigs against enzootic pneumonia. The systemic and local
      immune responses, as well as the efficacy of the chimaeric protein in inducing
      protection against experimental M. hyopneumoniae infection were evaluated. In
      total, 60 male piglets, purchased from a M. hyopneumoniae-free herd, at 4 weeks
      of age were randomly allocated to six different experimental groups of 10 animals
      each: recombinant chimaeric protein by intramuscular (IM) (1) or intranasal (IN)
      (2) administration, commercial bacterin by IM administration (3), and the
      adjuvant LTB by IM (4, control group A) or IN (5, control group B)
      administration. All groups were immunized at 24 and 38 days of age and challenged
      at 52 days of age. The sixth group that was not challenged was used as the
      negative control (IN [n=5] or IM [n=5] administration of the LTB adjuvant).
      Compared with the non-challenged group, administration of the chimaeric protein
      induced significant (P<0.05) IgG and IgA responses against all individual
      antigens present in the chimaera, but it could not confer a significant
      protection against M. hyopneumoniae infection in pigs. This lack of effectiveness
      points towards the need for further studies to improve the efficacy of this
      subunit-based vaccine approach.

PMID- 24909333
TI  - Dynamic stability and compensatory stepping responses during anterior gait-slip
      perturbations in people with chronic hemiparetic stroke.
AB  - To examine the control of dynamic stability and characteristics of the
      compensatory stepping responses to an unexpected anterior gait slip induced under
      the non-involved limb in people with hemi-paretic stroke (PwHS) and to examine
      any resulting adaptive changes in these on the second slip due to experience from
      prior slip exposure. Ten PwHS experienced overground slip (S1) during walking on
      the laboratory walkway after 5-8 regular walking (RW) trials followed by a second
      consecutive slip trial (S2). The slip outcome (backward loss of balance, BLOB and
      no loss of balance, NLOB) and COM state (i.e. its COM position and velocity)
      stability were examined between the RW and S1 and S1 and S2 at touchdown (TD) of
      non-involved limb and at liftoff (LO) of the contralateral limb. At TD there was
      no difference in stability between RW and S1, however at LO, subjects
      demonstrated a lower stability on S1 than RW resulting in a 100% backward loss of
      balance (BLOB) with compensatory stepping response (recovery step, RS, 4/10 or
      aborted step, AS, 6/10). On S2, although there was no change in stability at TD,
      there was a significant improvement in stability at LO with a 40% decrease in
      BLOB. There was also a change in step strategy with a decrease in AS response
      (60% to 35%, p<0.05) which was replaced by an increase in the ability to step
      (increased compensatory step length, p<0.05) either via a recovery step or a
      walkover step. PwHS have the ability to reactively control COM state stability to
      decrease fall-risk upon a novel slip; prior exposure to a slip did not
      significantly alter feedforward control but improved the ability to use such
      feedback control for improved slip outcomes. 

PMID- 24909332
TI  - The morphology of the thumb carpometacarpal joint does not differ between men and
      women, but changes with aging and early osteoarthritis.
AB  - The high prevalence of thumb carpometacarpal (CMC) joint osteoarthritis (OA) in
      women has been previously linked to the articular morphology of the trapezium.
      Studies report conflicting results on how the articular shapes of male and female
      trapezia compare to one another, however, mainly because their findings are based
      on data from older cadaveric specimens. The purpose of this in vivo study was to
      dissociate the effect of sex from that of aging and early OA by using cohorts of
      healthy young and healthy older subjects, as well as patients with early stage
      OA. Computed tomography scans from 68 healthy subjects and 87 arthritic subjects
      were used to obtain 3-D bone models. The trapezial and metacarpal articular
      surfaces were manually delineated on scaled bone models and compared between sex,
      age, and health groups by using polar histograms of curvature and average
      curvatures. We found no sex-related differences, but significant age-group and
      health-group differences, in the articular surfaces of both bones. Older healthy
      subjects had higher curvature in the concave and lower curvature in the convex
      directions of both the trapezial and metacarpal saddles than healthy young
      subjects. Subjects with early OA had significantly different metacarpal and
      trapezial articular shapes from healthy subjects of the same age group. These
      findings suggest that aging and OA affect the articular shape of the CMC joint,
      but that, in contrast to previously held beliefs, inherent sex differences are
      not responsible for the higher incidence of CMC OA in women. 

PMID- 24909334
TI  - Secondary malignant transformation of testicular teratomas: case series and
      literature review.
AB  - BACKGROUND: Teratomas are a spectrum of neoplasms that can undergo malignant
      transformation. In the World Health Organization (WHO) classification of tumors,
      this entity was classified as "teratoma with somatic-type malignancy", was
      defined as a malignant neoplasm of non-germinal phenotype that originates in a
      teratoma. MATERIALS AND METHODS: We present a serie of nine cases of testicular
      teratomas with secondary malignant transformation. From January 1995 to December
      2011, we found a total of 306 cases of testicular tumors. Mixed germ cell tumors
      were the most frequently diagnosed malignancy with 45.7%. RESULTS: Teratoma with
      secondary malignant transformation, represented 2.9% of all germinal tumors. Five
      cases originated within a mixed germ cell tumor, two cases from mature teratomas,
      and two from immature teratomas. The predominante malignant somatic component
      were sarcomas; two cases of chondrosarcoma, one rhabdomyosarcoma, and one case
      showing foci of chondrosarcoma and rhabdomyosarcoma. The case of osteosarcoma is
      notable for its rarity. Two cases showed epithelial malignancy in the form of an
      adenocarcinoma, and finally, two cases were primitive neuroectodermal tumors. At
      the time of diagnosis, five patients had metastases. CONCLUSION: The
      transformation of germ cell tumors to somatic type malignancies is rare. The
      malignant component can originate from any of the three germ lines. These tumors
      are resistant to standard chemotherapy for a germ cell tumor and the clinical
      stage is the most important prognostic factor. At our institution, the malignant
      component that appeared most frequently was chondrosarcoma.

PMID- 24909335
TI  - Evolution of the patient characteristics of candidates for radical prostatectomy
      and the results obtained with the technique.
AB  - OBJECTIVES: To evaluate the oncological profile and risk of biochemical
      recurrence of patients with prostate cancer who underwent radical prostatectomy
      based on the time period in which the patients were operated. To evaluate the
      differences in prostate-specific antigen (PSA) at diagnosis of patients with or
      without biochemical recurrence based on these time periods. MATERIAL AND METHODS:
      Observation carried forward study of a cohort of 972 radical prostatectomies
      performed during 3 time periods (1994-2000, 2001-2006, 2007-2011). The importance
      of PSA at diagnosis on the time periods and on biochemical recurrence was
      assessed using a generalized linear model. The independent predictive behavior of
      biochemical recurrence was analyzed using Cox regression. RESULTS: The median
      follow-up was 38 (16-76) months. PSA levels at diagnosis were higher in the
      period 1994-2000 (12.97ng/mL, P<.001). Seventy-two percent of the patients from
      the period 2007-2011 were diagnosed as clinical stage T1c (P<.001), compared with
      55% from the period 1994-2000. The percentage of extracapsular extension in the
      specimen decreased from 27% to 18% from the period 1994-2000 to the period 2007
      2011 (p<.001). The percentage of patients with biochemical recurrence went from
      38% to 14% from the first to the third period (P>.001). The difference between
      PSA levels at diagnosis for the patients with or without biochemical recurrence
      was independent of the period (P=.84). The period during which surgery was
      performed was not an independent predictive factor for biochemical recurrence
      (P=.09). CONCLUSIONS: Patients from the 2007-2011 period had less extracapsular
      disease in the radical prostatectomy. The period was not an independent
      predictive factor for biochemical recurrence.

PMID- 24909337
TI  - The Interaction of Implant Luting Cements and Oral Bacteria Linked to Peri
      Implant Disease: An In Vitro Analysis of Planktonic and Biofilm Growth--A
      Preliminary Study.
AB  - BACKGROUND: There is little consensus on the most appropriate cement to use when
      restoring a cement-retained, implant-supported restoration. One consideration
      should be the interaction of pathogenic oral bacteria with restorative cements.
      PURPOSE: To determine how oral bacteria associated with peri-implant disease grow
      in the presence of implant cements. MATERIALS AND METHODS: Five test cements with
      varying composition (zinc oxide-eugenol [TBO], eugenol-free zinc oxide [TBNE],
      zinc orthophosphate [FL], and two resin cements [PIC and ML]) were used to
      fabricate specimen disks. The disks were submerged in bacterial suspensions of
      either Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, or
      Porphyromonas gingivalis. Planktonic bacterial growth within the test media was
      measured by determining the optical density of the cultures (OD600 ). Positive
      controls (media and bacteria without cement disks) and negative controls (media
      alone) were similarly evaluated. The mean and standard deviations (SD) were
      calculated for planktonic growth from three separate experiments. ANOVA
      statistical analysis with post hoc Tukey tests was performed where differences
      existed (p < .05). Selected cement disks (TBO and ML) were further examined for
      bacterial biofilm growth. Surface bacteria were removed and grown on agar media,
      and colony-forming units (CFUs) were quantified. RESULTS: Planktonic growth for
      both A. actinomycetemcomitans and P. gingivalis was significantly inhibited (p <
      .05) when grown in the presence of cement disks consisting of TBNE, PIC, FL, and
      TBO. In contrast, neither of these bacteria displayed growth inhibition in the
      presence of ML cement disks. F. nucleatum growth was also significantly inhibited
      by PIC, FL. and TBO (p < .05), but not by ML and TBNE cement disks. CFU counts
      for the biofilm study for TBO gave minimal and, in some instances, no bacterial
      adherence and growth, in contrast to ML, which supported substantially greater
      bacterial biofilm growth. CONCLUSION: Cements display differing abilities to
      inhibit both planktonic and biofilm bacterial growth. Cements with the ability to
      reduce planktonic or biofilm growth of the test bacteria may be advantageous in
      reducing peri-implant disease. Understanding the microbial growth-inhibiting
      characteristics of different cement types should be considered important in the
      selection criteria.

PMID- 24909338
TI  - The complicated Allen-Masters syndrome: small bowel herniation through a broad
      ligament defect.
AB  - Small bowel obstruction through a broad ligament defect is a very rare condition.
      We present 2 cases, one without any associated abdominal trauma. Rapid diagnosis
      and treatment of this rare condition is of paramount importance. 

PMID- 24909336
TI  - Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The 7th American Joint Committee on Cancer (AJCC) currently
      classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic
      cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two
      carcinomas have shown contrary results. This study was designed to compare the
      survival and prognostic factors of both carcinomas. METHODS: We retrospectively
      reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent
      liver resection between January 2000 and December 2009. RESULTS: Thirty patients
      (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free
      survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall
      survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and
      ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and
      lymph node (LN) metastasis were prognostic factors in all patients. However,
      tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9,
      differentiation and LN metastasis in ICC patients were found to be independent
      prognostic factors. CONCLUSIONS: Patients with cHCC-CC showed poorer DFS and
      similar OS rates compared to those with ICC. Our study revealed different
      prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis,
      difference of genetic characteristics and tumor biology should be further
      evaluated.

PMID- 24909339
TI  - Differential expression of caveolin-1 in human myometrial and uterine leiomyoma
      smooth muscle.
AB  - OBJECTIVE: Uterine leiomyomas, the most common neoplasms of the female genital
      tract, are benign tumors of the uterus arising from the smooth muscle cells
      (SMCs) of the myometrium with an involvement of estrogen. Caveolin-1 (Cav-1), a
      major protein component in caveolae membrane lipid rafts, is down-regulated in
      several estrogen-related cancer cells, and overexpression of Cav-1 inhibits
      proliferation of cancer cells and vascular SMCs as well. Therefore, we
      hypothesize that Cav-1 is down-regulated in human uterine leiomyoma. RESULTS:
      Western blot using tissues from clinical patients showed that Cav-1 expression
      was significantly lower or undetectable in uterine leiomyoma compared with their
      matched myometrium (P < .001). This finding was confirmed by immunohistochemistry
      and confocal microscopy. The cav-1 mRNA level in uterine leiomyomas was also
      significantly lower as detected by reverse transcription-quantitative polymerase
      chain reaction analysis (P = .001). To further study the underlying mechanism, we
      performed primary cell culture, and found that the expression of Cav-1 remained
      low in cultured leiomyoma SMCs (P = .009). Serum withdrawal did not change Cav-1
      expression in leiomyoma SMCs, but increased expression in myometrial SMCs (P =
      .006). 17-beta estradiol inhibited the expression of Cav-1 protein (P = .047) and
      mRNA (P = .007) in leiomyoma SMCs, whereas it stimulated expression in myometrial
      SMCs (P = .043). 17-beta estradiol, although activating the mitogen-activated
      protein kinase pathway in both SMCs, did not stimulate their proliferation.
      CONCLUSION: We conclude that human uterine leiomyomas in vitro express low levels
      of Cav-1, which may result from estrogen inhibition. This effect of estrogen may
      contribute to the pathogenesis of uterine leiomyoma. Further studies in vivo are
      needed to verify these results.

PMID- 24909340
TI  - The mortality risk of expectant management compared with delivery stratified by
      gestational age and race and ethnicity.
AB  - OBJECTIVE: The objective of the study was to compare the mortality risk of
      expectant management with the risk of delivery at each week of term pregnancy in
      4 racial/ethnic groups. STUDY DESIGN: This was a retrospective cohort study of
      all nonanomalous, term deliveries in California from 1997 to 2006 among white,
      black, Hispanic, and Asian women. In each racial/ethnic group, we compared the
      risk of infant death at each week with a composite risk representing the
      mortality risk of 1 week of expectant management. RESULTS: The risk of stillbirth
      and infant death is highest in black women (stillbirth risk: 18.0 per 10,000,
      infant death: 24.4 per 10,000, compared with 9.4 per 10,000 and 10.8 per 10,000
      in white women, respectively; P < .001). Although absolute risks differ by
      race/ethnicity, the composite risk of expectant management does not surpass the
      risk of delivery until 39 weeks in any group. At 39 weeks these absolute risk
      differences are low, however, with a number needed to deliver to prevent 1 death
      ranging from 751 (among black women) to 2587 (among Asian women). CONCLUSION: The
      mortality risk of expectant management exceeds the risk of delivery at 39 weeks
      in all racial/ethnic groups, despite variation in absolute risks.

PMID- 24909341
TI  - Performance of racial and ethnic minority-serving hospitals on delivery-related
      indicators.
AB  - OBJECTIVE: We sought to explore how racial/ethnic minority-serving hospitals
      perform on 15 delivery-related indicators, and examine whether indicators vary by
      race/ethnicity within the same type of hospitals. STUDY DESIGN: We used 2008
      through 2011 linked State Inpatient Database and American Hospital Association
      data from 7 states, and designated hospitals with >50% of deliveries to non
      Hispanic white, non-Hispanic black, and Hispanic women as white-, black-, and
      Hispanic-serving, respectively. We calculated indicator rates per 1000 deliveries
      by hospital type and, separately, for non-Hispanic white, non-Hispanic black, and
      Hispanic women within each hospital type. We fitted multivariate Poisson
      regression models to examine associations between delivery-related indicators and
      patient and hospital characteristics by hospital type. RESULTS: White-serving
      hospitals offer obstetric care to an older and wealthier population than black-
      or Hispanic-serving hospitals. Rates of the most prevalent indicators examined
      (complicated vaginal delivery, complicated cesarean delivery, obstetric trauma)
      were lowest in Hispanic-serving hospitals. Generally, indicator rates were
      similar in Hispanic- and white-serving hospitals. Black-serving hospitals
      performed worse than other hospitals on 12 of 15 indicators. Indicator rates
      varied greatly by race/ethnicity in white- and Hispanic-serving hospitals, with
      non-Hispanic blacks having 1.19-3.27 and 1.15-2.68 times higher rates than non
      Hispanic whites, respectively, for 11 of 15 indicators. Conversely, there were
      few indicator rate differences by race/ethnicity in black-serving hospitals,
      suggesting an overall lower performance of these hospitals compared to white- and
      Hispanic-serving hospitals. CONCLUSION: We found considerable differences in
      delivery-related indicators by hospital type and patients' race/ethnicity.
      Obstetric care quality measures are needed to track racial/ethnic disparities at
      the facility and population levels.

PMID- 24909342
TI  - Exercise in pregnancies complicated by obesity: achieving benefits and overcoming
      barriers.
AB  - An increasing number of women are entering pregnancy in an overweight or obese
      state. Obese women and their offspring are at increased risk of adverse perinatal
      outcomes, which may be improved by regular moderate-intensity antenatal exercise.
      Current guidelines recommend that all pregnant women without contraindications
      engage in >=30 minutes of moderate-intensity exercise on a daily basis. However,
      obese women are usually less physically active and tend to further reduce
      activity levels during pregnancy. This commentary summarizes the potential short-
      and long-term benefits of antenatal exercise in obese pregnant women, highlights
      the challenges they face, and discusses means of improving their exercise levels.
      In addition, we make recommendations on exercise prescription for pregnancies
      complicated by obesity. 

PMID- 24909343
TI  - Moral bioenhancement: much ado about nothing?
AB  - Recently, some have proposed moral bioenhancement as a solution to the serious
      moral evils that humans face. Seemingly disillusioned with traditional methods of
      moral education, proponents of bioenhancement believe that we should pursue and
      apply biotechnological means to morally enhance human beings. Such proposal has
      generated a lively debate about the permissibility of moral bioenhancement. We
      argue here that such debate is specious. The claim that moral bioenhancement is a
      solution - whether permissible or not - to the serious moral problems that affect
      human beings is based on several problematic framing assumptions. We evaluate
      here three of such assumptions: the first rests on a contested understanding of
      morality, the second consist in a mistaken conception of human moral problems,
      and the third relates to problematic presuppositions grounding the interpretation
      of existent scientific evidence presented to defend moral bioenhancement. Once
      these framing assumptions are identified and critically evaluated, it becomes
      clear that the moral bioenhancement debate is misguided. 

PMID- 24909344
TI  - Reduced binding of human antibodies to cells from GGTA1/CMAH KO pigs.
AB  - Xenotransplantation using genetically modified pig organs could solve the donor
      organ shortage problem. Two inactivated genes that make humans unique from pigs
      are GGTA1 and CMAH, the products of which produce the carbohydrate epitopes, aGal
      and Neu5Gc that attract preformed human antibody. When the GGTA1 and CMAH genes
      were deleted in pigs, human antibody binding was reduced in preliminary analysis.
      We analyzed the binding of human IgM and IgG from 121 healthy human serum samples
      for binding to GGTA1 KO and GGTA1/CMAH KO peripheral blood mononuclear cells
      (PBMCs). We analyzed a sub population for reactivity toward genetically modified
      pig PBMCs as compared to chimpanzee and human PBMCs. Deletion of the GGTA1 and
      CMAH genes in pigs improved the crossmatch results beyond those observed with
      chimpanzees. Sorting the 121 human samples tested against the GGTA1/CMAH KO pig
      PBMCs did not reveal a distinguishing feature such as blood group, age or gender.
      Modification of genes to make pig carbohydrates more similar to humans has
      improved the crossmatch with human serum significantly. 

PMID- 24909345
TI  - Association of varicosities and concomitant deep venous thrombosis in patients
      with superficial venous thrombosis, a systematic review.
AB  - BACKGROUND: In patients with superficial venous thrombosis (SVT) co-existence of
      deep venous thrombosis (DVT) can be present. Varicosities are considered as a
      risk factor for both SVT and DVT separately. However, current evidence is
      contradictory whether varicosities are associated with an increased or reduced
      prevalence of concomitant DVT in patients with SVT. OBJECTIVES: To determine the
      diagnostic value of both presence and absence of varicosities in the detection of
      concomitant DVT in non-hospitalized patients with SVT. METHODS: In MEDLINE and
      EMBASE, a systematic search was performed to collect all published studies on
      this topic. The selected papers were critically appraised. By diagnostic 2 * 2
      tables prior probabilities and predictive values were computed. RESULTS: Six
      relevant articles were identified. The prior probability of concomitant DVT in
      patients referred from primary care to the outpatient clinic varied between 13
      and 34%. In five studies, absence of varicosities was related to a higher
      probability of concomitant DVT (33-44%) compared to a presence of varicosities (3
      23%). The sixth study showed an inversed, non-significant association: DVT was
      present in 21% of patients with SVT on non-varicose veins versus in 35% of
      patients with SVT on varicose veins. CONCLUSION: In five out of six studies on
      patients with SVT in outpatient settings, absence of varicosities was related to
      a higher probability of concomitant DVT. Further research is needed to determine
      whether an assessment of varicosities in general practice could result in an
      improved selection of patients who require additional imaging to detect or
      exclude DVT.

PMID- 24909346
TI  - Molecularly designed nanoparticles by dispersion of self-assembled organosiloxane
      based mesophases.
AB  - The design of siloxane-based nanoparticles is important for many applications.
      Here we show a novel approach to form core-shell silica nanoparticles of a few
      nanometers in size through the principle of "dispersion of ordered mesostructures
      into single nanocomponents". Self-assembled siloxane-organic hybrids derived from
      amphiphilic alkyl-oligosiloxanes were postsynthetically dispersed in organic
      solvent to yield uniform nanoparticles consisting of dense lipophilic shells and
      hydrophilic siloxane cores. In situ encapsulation of fluorescent dyes into the
      nanoparticles demonstrated their ability to function as nanocarriers. 

PMID- 24909347
TI  - Technical considerations of living donor hepatectomy of segment 2 grafts for
      infants.
AB  - BACKGROUND: The selection of an adequate graft to mitigate the problems
      associated with a large-for-size graft is essential to ensure the success of
      liver transplantation for smaller children. Reduced left lateral segment (LLS)
      grafts have been introduced to overcome this issue. METHODS: Five infants
      underwent living donor liver transplantation (LDLT) with segment 2 grafts. In the
      preoperative assessment, the graft-to-recipient weight ratio (GRWR) and the ratio
      of the thickness of the donor LLS were used as a reference index for graft size
      matching, and a 3-dimensional (3D) computer-generated model of the donor liver
      was used for the analysis of the intrahepatic vasculature. During the donor
      operation, the relevant portal vein branches feeding to the reduced part of
      segment 3 were first exposed and divided, and then the parenchymal transection
      was performed. RESULTS: Segment 2 grafts were selected in 3 cases and reduced
      segment 2 grafts were selected in the other 2 cases. The graft reduction was
      achieved with 46.6 +/- 8.2% of the actual LLS, and thus the GRWR was reduced from
      5.33 +/- 2.09% to 2.70 +/- 0.82%. The actual graft thickness was reduced by
      approximately half after the graft reduction. Primary abdominal closure was
      performed in all of the recipients. No surgical complications occurred in any of
      the donors or recipients. CONCLUSION: A segment 2 graft could be a valuable
      option for graft type selection in LDLT for smaller children. Precise planning
      using a 3D computer-generated model of the donor liver and meticulous operative
      procedures are necessary to obtain a viable graft.

PMID- 24909349
TI  - Congenital duplication of the larynx.
AB  - INTRODUCTION: The larynx is an intricate structure serving three important
      functions in humans: it protects the lower respiratory airway, facilitates
      respiration and helps produce sound through a key role in phonation. OBJECTIVE:
      We report the first published finding of congenital duplication of the larynx in
      a patient with previously cleared squamous cell carcinoma of the neck and a new
      diagnosis of squamous cell carcinoma of the lung. CASE REPORT: We describe the
      incidental finding of duplication of the larynx in a 62-year-old man with
      previously completely cleared squamous cell carcinoma of the neck, who presented
      with worsening dyspnoea. We also provide a brief overview of other published
      cases in which duplication of the vocal folds and epiglottis has been reported.
      RESULTS: Our patient experienced no symptoms related to this incidental finding
      of congenital duplication of the larynx. CONCLUSION: The first case of congenital
      duplication of the larynx is currently of academic interest only; however, the
      possible association with squamous cell carcinoma is postulated to raise
      awareness in clinicians who may observe further cases in the future.

PMID- 24909348
TI  - Introduction of a comprehensive training curriculum in laparoscopic surgery for
      medical students: a randomized trial.
AB  - BACKGROUND: First- and second-year medical students have limited exposure to
      basic surgical skills. An introductory, comprehensive, simulation-based
      curriculum in basic laparoscopic skills may improve medical students' knowledge
      and technical and nontechnical skills and may raise their interest in a career in
      surgery. The purpose of this study was to (1) design a comprehensive, simulation
      based training curriculum (STC) aimed to introduce junior medical students to
      basic laparoscopic skills and (2) compare structured and supervised learning and
      practice to a self-directed approach. METHODS: Twenty-four, pre-clerkship medical
      students were allocated randomly to either a supervised (STC) or a self-directed
      learning and practice (SDL) group. Participants in the STC group received
      structured training in cognitive, and basic technical and nontechnical domains of
      laparoscopic surgery, whereas the SDL group was invited to engage in SDL in the
      same domains. RESULTS: At post-training assessment, basic knowledge about
      laparoscopic surgery, and attitudes toward nontechnical skills were equivalent
      between STC and SDL groups. The STC group outperformed (mean +/- standard
      deviation) the SDL group on a peg transfer task (58 +/- 13 vs 81 +/- 19 seconds;
      P = .005). Participants in the STC group showed significant within-group
      improvements in knowledge, technical skill, and in 4 of 5 domains of nontechnical
      skills, whereas participants in the SDL group showed significant within-group
      improvement in technical skill and in 1 of 5 domains of nontechnical skills.
      CONCLUSION: Participation in the STC resulted in significant gains in knowledge,
      technical skill, and attitudes toward nontechnical skills. Exposure of junior
      medical students to this curriculum before their clinical rotations is expected
      to enhance learning, maintain motivation, and increase interest in surgery as a
      future career.

PMID- 24909350
TI  - The effect of photodynamic therapy on cisterna chyli patency in rats.
AB  - OBJECTIVE: To radiographically and histologically evaluate the effects of
      photodynamic therapy on the cisterna chyli in rats. STUDY DESIGN: Experimental
      study. ANIMALS: Adult male Sprague-Dawley rats (n = 60). METHODS: Cecal lymph
      nodes were injected with the photodynamic compound verteporfin. A 690 nm, 500 mW
      diode laser was then directed at the area of the cisterna chyli for either 0,
      1.5, or 3 minutes. Cisterna chyli patency was evaluated using lymphography, and
      histologic changes were evaluated on postoperative Days 1, 3, 5, 7, and 14.
      RESULTS: Histologically, minimal to marked injury to the cisternal and/or
      pericisternal tissues was present in all treated rats at all time periods.
      Radiographically, 8/20 cisternae were occluded in the 1.5-minute treatment group
      (including 1/4 on Day 1, 2/4 on Day 3, 3/4 on Day 5, 0/4 on Day 7, and 2/4 on Day
      14), and 9/20 cisternae were occluded in the 3-minute treatment group (including
      0/4 on Day 1, 1/4 on Day 3, 3/4 on Day 5, 3/4 on Day 7, and 2/4 on Day 14). There
      was minimal to no histologic evidence of tissue injury in control rats. All
      control cisternae were radiographically open. CONCLUSIONS: Further investigations
      into the timing of laser application and light dose, or alternative photodynamic
      agents are required to limit injury to adjacent tissues and to improve the
      effectiveness of cisternal photoablation.

PMID- 24909352
TI  - Reducing task difficulty during practice improves motor learning in older adults.
AB  - Theoretically, greater motor output variability can inhibit motor learning by
      inhibiting task acquisition during practice. Although the age-associated
      differences in motor output variability exacerbate with more difficult tasks, it
      remains unknown whether task difficulty during task acquisition influences motor
      learning in older adults. The purpose of this study was to determine whether the
      difficulty of the practice task affects motor learning in older adults. Twenty
      four older (72.7+/-7.4years; 11 women) and 7 young (23.1+/-4years; 1 man) adults
      participated in this study. Participants were divided into four groups: 8 older
      adults who practiced an easy task (O-Easy), 8 older adults who practiced a harder
      task (O-Hard), 8 older adults who did not practice (O-None), and 7 young adults
      who did not practice (Y-None). The level of difficulty depended on the relative
      timing (i.e. phase) of abduction force generation between the index and little
      fingers to track a moving target on the monitor. The O-Easy group practiced the
      task with 0 degrees , whereas the O-Hard group practiced the task with 90 degrees
      relative phase. Practice occurred within a single session for 80 trials. Motor
      learning was quantified as the ability to transfer the practiced tasks to 45
      degrees , 135 degrees  and 180 degrees  relative phases 24 and 168h after
      acquisition. Only the O-Easy group was able to significantly transfer the
      practiced task, as it was indicated by significantly lower force variability and
      error during all transfer tasks compared with the O-None group (P<0.05). The O
      Hard group was not significantly different from the O-None group (P>0.2). In
      addition, during the transfer tasks the O-Easy group exhibited performance
      similar to that of the young adults who did not practice. These findings suggest
      that practice with easier tasks may be advantageous to practice with more
      difficult tasks to improve motor learning in older adults. 

PMID- 24909351
TI  - Temperature fluctuations in the lower limbs of young and elderly individuals
      during activities of daily living.
AB  - Age-related deficiencies in thermoregulation diminish the capacity to defend
      against heat loss under conditions often encountered during activities of daily
      living (ADL). A potential consequence of these deficiencies is that elderly
      individuals could have colder lower limbs, which would exacerbate the age-related
      decline in plantarflexor contractile properties and compromise recovery from a
      tripping incident. Moreover, a common self-perception among the elderly is that
      their limbs are cold. However, this impression has never been documented,
      especially under ADL conditions. Our objective was to test the hypothesis that
      elderly individuals have lower plantarflexor temperatures than their younger
      counterparts. Skin temperatures above the plantarflexors of elderly and young
      individuals were continuously recorded during ADL in the winter months and
      compared under three conditions: quiescent indoor temperature, during a cold
      challenge, and the recovery period subsequent to the cold challenge. For
      quiescent indoor periods, differences in skin temperature between the two groups
      were not statistically significant. During cold exposures, both age and exposure
      duration were statistically significant factors related to the decrease in skin
      temperature, with the elderly group maintaining warmer temperatures. In the
      recovery period following short duration cold exposures, a statistically
      significant difference between the two groups for the decrease in skin
      temperature persisted for the first 9min of recovery. The results do not support
      the hypothesis that the lower limbs of elderly participants are colder. Higher
      limb temperatures observed in elderly participants were consistent with previous
      studies of age-related thermoregulatory changes, indicating that deficiencies in
      vasoconstriction are persistent in ADL. 

PMID- 24909353
TI  - Do subclinical vascular abnormalities precede impaired physical ability and ADL
      disability?
AB  - Cardiovascular disease is an important cause of disability in activities of daily
      living (ADL) through its effect on physical functioning. However, it is unclear
      whether subclinical vascular abnormalities and rate of change in subclinical
      vascular abnormalities is also associated with an impaired physical ability and
      with ADL disability. In a longitudinal study, 490 middle-aged and older persons
      were included. Physical ability was measured using the Short Physical Performance
      Battery and ADL disability using a questionnaire on self-reported basic and
      instrumental ADL. Subclinical vascular abnormalities were measured by pulse wave
      velocity (PWV) and carotid intima media thickness (CIMT, in men only).
      Longitudinal associations between baseline markers of subclinical vascular
      abnormalities, their rate of change, and change in physical ability or ADL
      disability were assessed using generalized estimation equation models. After
      adjustment for confounders, higher baseline PWV, change in PWV, baseline CIMT (in
      men) and change in CIMT (in men) were associated with a higher rate of change in
      physical ability (regression coefficients 0.035, 95% CI [0.018; 0.052]; 0.047,
      95% CI [0.024; 0.069]; 0.214, 95% CI [0.070; 0.358] and 0.148, 95% CI [0.019;
      0.277], respectively). No relations were found for change in ADL disability. In
      subjects with incident cardiovascular disease, higher change in PWV was
      associated with a higher rate of change in ADL disability (regression coefficient
      0.054, 95% CI [0.001; 0.106]). The present study showed that subclinical vascular
      abnormalities and rate of change were associated with higher rate of change in
      physical ability. The association between (change in) subclinical vascular
      abnormalities and ADL disability tended to be stronger in persons with incident
      and prevalent cardiovascular disease. These data may suggest that ADL decline is
      more a direct effect of experienced clinically manifest vascular events rather
      than the effect of progression of subclinical vascular abnormalities. 

PMID- 24909354
TI  - Endovascular venous thrombolysis in children younger than 24 months.
AB  - PURPOSE: To evaluate the technical feasibility and safety of percutaneous
      endovascular thrombolysis for extremity deep venous thrombosis (DVT) in children
      < 24 months old. MATERIALS AND METHODS: A retrospective chart review of a
      clinical and imaging database was performed for pediatric patients who underwent
      endovascular therapy for DVT between January 2010 and July 2013. Indications,
      techniques, technical and clinical success, and complications were reviewed.
      Techniques for thrombolysis included catheter-directed therapy (CDT) using
      alteplase infusion via a multi-side hole catheter, mechanical thrombectomy, and
      angioplasty. Short-term outcomes were assessed using surgical and imaging follow
      up examinations for patency of the targeted vessel. Patients included 11 children
      (mean age, 9 mo; range, 3 wk-23 mo) who consecutively underwent endovascular
      thrombolysis for upper extremity (n = 6) or lower extremity (n = 5) DVT. The most
      common indication was preservation of venous access for future cardiac surgery or
      medical therapy. RESULTS: The most common risk factor was the presence of a
      central venous catheter (10 of 11 patients). All patients with upper extremity
      DVT had congenital heart disease. CDT and angioplasty were performed in all
      patients. Venous patency was established in all patients. A grade III (95%-100%)
      thrombolysis response was achieved in seven patients, and a grade II (50%-95%)
      thrombolysis response was achieved in four patients. A major complication of
      pulmonary embolism occurred in one patient with upper extremity thrombolysis and
      was managed by intravenous systemic alteplase and heparin. No recurrence of
      thrombosis was found on average follow-up of 11.8 months (range, 1-41 mo).
      CONCLUSIONS: Percutaneous endovascular thrombolysis for extremity DVT is safe and
      technically feasible in children < 24 months old.

PMID- 24909355
TI  - Recovery of lead-induced suppressed reproduction in male rats by testosterone.
AB  - The objective of the present study was to investigate the effects of testosterone
      in recuperation of lead-induced suppressed reproduction in adult male rats. Lead
      acetate was administered orally to adult male rats (95 +/- 5 days) at dosage
      level of 0.05 and 0.15% for 55 days through drinking water and injected
      intraperitoneally with either testoviron depot at a dose of 4.16 mg kg(-1) body
      weight or vehicle alone on days 1, 7 and 14 respectively. At the end of
      treatment, control and treated males were cohabited with untreated normal-cycling
      females. After cohabitation for 5 days, all the male rats were killed and weights
      of reproductive organs were determined. Significant increase in the indices of
      testis, epididymis, seminal vesicles, vas deferens and prostate glands was
      observed in testosterone (T)-treated rats when compared to those of lead-exposed
      rats. Testosterone treatment significantly increased epididymal sperm count,
      motile spermatozoa, viable spermatozoa and HOS tail-coiled spermatozoa and also
      the activity levels of testicular 3beta- and 17beta-hydroxysteroid dehydrogenases
      when compared to those of lead-exposed males. From the results, it can be
      hypothesised that supplementation of testosterone mitigated lead-induced
      suppressed reproduction in male rats. 

PMID- 24909356
TI  - MicroRNAs as oncogenes or tumour suppressors in oesophageal cancer: potential
      biomarkers and therapeutic targets.
AB  - MicroRNAs are a class of small, non-coding RNAs that can negatively regulate
      protein-coding genes, and are associated with almost all known physiological and
      pathological processes, especially cancer. The number of studies documenting
      miRNA expression patterns in malignancy continues to expand rapidly, with
      continuously gained critical information regarding how aberrantly expressed
      miRNAs may contribute to carcinogenesis. miRNAs can influence cancer
      pathogenesis, playing a potential role as either oncogenes or tumour suppressors.
      Recently, several miRNAs have been reported to exert different regulatory
      functions in oesophageal cancer - the carcinoma typically arising from the
      epithelial lining of the oesophagus. These miRNAs also have potential clinical
      applications towards developing biomarkers or targets for possible use in
      diagnosis or therapy in oesophageal cancer. In this review, we have summarized
      the two (oncogenic or tumour suppressive) roles of miRNAs here, and their
      applications as potential biomarkers or therapeutic targets, which may illuminate
      future treatment for oesophageal cancer. 

PMID- 24909357
TI  - T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided
      focused ultrasound.
AB  - Precise focusing is essential for transcranial MRI-guided focused ultrasound
      (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve
      temperatures capable of inducing coagulative necrosis at acceptable power
      deposition levels. CT is usually used for this refocusing but requires a separate
      study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to
      determine whether MRI using an appropriate sequence would be a viable alternative
      to CT for planning ultrasound refocusing in TcMRgFUS. We tested three MRI pulse
      sequences (3D T1 weighted 3D volume interpolated breath hold examination (VIBE),
      proton density weighted 3D sampling perfection with applications optimized
      contrasts using different flip angle evolution and 3D true fast imaging with
      steady state precision T2-weighted imaging) on patients who have already had a CT
      scan performed. We made detailed measurements of the calvarial structure based on
      the MRI data and compared those so-called 'virtual CT' to detailed measurements
      of the calvarial structure based on the CT data, used as a reference standard. We
      then loaded both standard and virtual CT in a TcMRgFUS device and compared the
      calculated phase correction values, as well as the temperature elevation in a
      phantom. A series of Bland-Altman measurement agreement analyses showed T1 3D
      VIBE as the optimal MRI sequence, with respect to minimizing the measurement
      discrepancy between the MRI derived total skull thickness measurement and the CT
      derived total skull thickness measurement (mean measurement discrepancy: 0.025;
      95% CL (-0.22-0.27); p = 0.825). The T1-weighted sequence was also optimal in
      estimating skull CT density and skull layer thickness. The mean difference
      between the phase shifts calculated with the standard CT and the virtual CT
      reconstructed from the T1 dataset was 0.08 +/- 1.2 rad on patients and 0.1 +/-
      0.9 rad on phantom. Compared to the real CT, the MR-based correction showed a 1 
      degrees C drop on the maximum temperature elevation in the phantom (7% relative
      drop). Without any correction, the maximum temperature was down 6  degrees C (43%
      relative drop). We have developed an approach that allows for a reconstruction of
      a virtual CT dataset from MRI to perform phase correction in TcMRgFUS. 

PMID- 24909358
TI  - Optimal stimulation mode for obtaining galvanic ocular vestibular-evoked myogenic
      potentials: our experience.

PMID- 24909359
TI  - Mental health problems are associated with low-frequency fluctuations in reaction
      time in a large general population sample. The TRAILS study.
AB  - BACKGROUND: Increased intra-subject reaction time variability (RT-ISV) as
      coarsely measured by the standard deviation (RT-SD) has been associated with many
      forms of psychopathology. Low-frequency RT fluctuations, which have been
      associated with intrinsic brain rhythms occurring approximately every 15-40s,
      have been shown to add unique information for ADHD. In this study, we
      investigated whether these fluctuations also relate to attentional problems in
      the general population, and contribute to the two major domains of
      psychopathology: externalizing and internalizing problems. METHODS: RT was
      monitored throughout a self-paced sustained attention task (duration: 9.1 +/- 1.2
      min) in a Dutch population cohort of young adults (n=1455, mean age: 19.0 +/- 0.6
      years, 55.1% girls). To characterize temporal fluctuations in RT, we performed
      direct Fourier Transform on externally validated frequency bands based on
      frequency ranges of neuronal oscillations: Slow-5 (0.010-0.027 Hz), Slow-4 (0.027
      0.073 Hz), and three additional higher frequency bands. Relative magnitude of
      Slow-4 fluctuations was the primary predictor in regression models for
      attentional, internalizing and externalizing problems (measured by the Adult Self
      Report questionnaire). Additionally, stepwise regression models were created to
      investigate (a) whether Slow-4 significantly improved the prediction of problem
      behaviors beyond the RT-SD and (b) whether the other frequency bands provided
      important additional information. RESULTS: The magnitude of Slow-4 fluctuations
      significantly predicted attentional and externalizing problems and even improved
      model fit after modeling RT-SD first (R(2) change=0.6%, P<.01). Subsequently,
      adding Slow-5 explained additional variance for externalizing problems (R(2)
      change=0.4%, P<.05). For internalizing problems, only RT-SD made a significant
      contribution to the regression model (R(2)=0.5%, P<.01), that is, none of the
      frequency bands provided additional information. CONCLUSIONS: Low-frequency RT
      fluctuations have added predictive value for attentional and externalizing, but
      not internalizing problems beyond global differences in variability. This study
      extends previous findings in clinical samples of children with ADHD to
      adolescents from the general population and demonstrates that deconstructing RT
      ISV into temporal components can provide more distinctive information for
      different domains of psychopathology.

PMID- 24909360
TI  - Genetic variation in the ovine uncoupling protein 1 gene: association with
      carcass traits in New Zealand (NZ) Romney sheep, but no association with growth
      traits in either NZ Romney or NZ Suffolk sheep.
AB  - The uncoupling protein 1 (UCP1) plays an important role in the regulation of
      lipolysis and thermogenesis in adipose tissues. Genetic variation within three
      regions (the promoter, intron 2 and exon 5) of the ovine UCP1 gene (UCP1) was
      investigated using polymerase chain reaction-single-strand conformational
      polymorphism (PCR-SSCP) analyses. These revealed three promoter variants
      (designated A, B and C) and two intron 2 variants (a and b). The association of
      this genetic variation with variation in lamb carcass traits and postweaning
      growth was investigated in New Zealand (NZ) Romney and Suffolk sheep. The
      presence of B in a lamb's genotype was associated with decreased subcutaneous
      carcass fat depth (V-GR) (p = 0.004) and proportion of total lean meat yield of
      loin meat (p = 0.005), and an increased proportion of total lean meat yield of
      hind-leg meat (p = 0.018). In contrast, having two copies of C was associated
      with increased V-GR (p < 0.001) and proportion of total lean meat yield of
      shoulder meat (p = 0.009), and a decreased hind-leg yield (p = 0.032). No
      associations were found with postweaning growth. These results suggest that ovine
      UCP1 is a potential gene marker for carcass traits. 

PMID- 24909361
TI  - Oxygen isotope signatures of transpired water vapor: the role of isotopic non
      steady-state transpiration under natural conditions.
AB  - The oxygen isotope signature of water is a powerful tracer of water movement from
      plants to the global scale. However, little is known about the short-term
      variability of oxygen isotopes leaving the ecosystem via transpiration, as high
      frequency measurements are lacking. A laser spectrometer was coupled to a gas
      exchange chamber directly estimating branch-level fluxes in order to evaluate the
      short-term variability of the isotopic composition of transpiration (deltaE ) and
      to investigate the role of isotopic non-steady-state transpiration under natural
      conditions in cork-oak trees (Quercus suber) during distinct Mediterranean
      seasons. The measured delta(18) O of transpiration (deltaE ) deviated from
      isotopic steady state throughout most of the day even when leaf water at the
      evaporating sites was near isotopic steady state. High agreement was found
      between estimated and modeled deltaE values assuming non-steady-state enrichment
      of leaf water. Isoforcing, that is, the influence of the transpirational
      delta(18) O flux on atmospheric values, deviated from steady-state calculations
      but daily means were similar between steady state and non-steady state. However,
      strong daytime isoforcing on the atmosphere implies that short-term variations in
      deltaE are likely to have consequences for large-scale applications, for example,
      partitioning of ecosystem fluxes or satellite-based applications. 

PMID- 24909362
TI  - Metabolic network reconstruction, growth characterization and 13C-metabolic flux
      analysis of the extremophile Thermus thermophilus HB8.
AB  - Thermus thermophilus is an extremely thermophilic bacterium with significant
      biotechnological potential. In this work, we have characterized aerobic growth
      characteristics of T. thermophilus HB8 at temperatures between 50 and 85 degrees
      C, constructed a metabolic network model of its central carbon metabolism and
      validated the model using (13)C-metabolic flux analysis ((13)C-MFA). First, cells
      were grown in batch cultures in custom constructed mini-bioreactors at different
      temperatures to determine optimal growth conditions. The optimal temperature for
      T. thermophilus grown on defined medium with glucose was 81 degrees C. The
      maximum growth rate was 0.25h(-1). Between 50 and 81 degrees C the growth rate
      increased by 7-fold and the temperature dependence was described well by an
      Arrhenius model with an activation energy of 47kJ/mol. Next, we performed a (13)C
      labeling experiment with [1,2-(13)C] glucose as the tracer and calculated
      intracellular metabolic fluxes using (13)C-MFA. The results provided support for
      the constructed network model and highlighted several interesting characteristics
      of T. thermophilus metabolism. We found that T. thermophilus largely uses
      glycolysis and TCA cycle to produce biosynthetic precursors, ATP and reducing
      equivalents needed for cells growth. Consistent with its proposed metabolic
      network model, we did not detect any oxidative pentose phosphate pathway flux or
      Entner-Doudoroff pathway activity. The biomass precursors erythrose-4-phosphate
      and ribose-5-phosphate were produced via the non-oxidative pentose phosphate
      pathway, and largely via transketolase, with little contribution from
      transaldolase. The high biomass yield on glucose that was measured experimentally
      was also confirmed independently by (13)C-MFA. The results presented here provide
      a solid foundation for future studies of T. thermophilus and its metabolic
      engineering applications. 

PMID- 24909364
TI  - Chaperonins resculpt folding free energy landscapes to avoid kinetic traps and
      accelerate protein folding.

PMID- 24909363
TI  - 3 Echo: concept of operations for early care and evacuation of victims of mass
      violence.
AB  - This report describes the successful use of a simple 3-phase approach that guides
      the initial 30 minutes of a response to blast and active shooter events with
      casualties: Enter, Evaluate, and Evacuate (3 Echo) in a mass-shooting event
      occurring in Minneapolis, Minnesota USA, on September 27, 2012. Early
      coordination between law enforcement (LE) and rescue was emphasized, including
      establishment of unified command, a common operating picture, determination of
      evacuation corridors, swift victim evaluation, basic treatment, and rapid
      evacuation utilizing an approach developed collaboratively over the four years
      prior to the event. Field implementation of 3 Echo requires multi-disciplinary
      (Emergency Medical Services (EMS), fire and LE) training to optimize performance.
      This report details the mass-shooting event, the framework created to support the
      response, and also describes important aspects of the concepts of operation and
      curriculum evolved through years of collaboration between multiple disciplines to
      arrive at unprecedented EMS transport times in response to the event.

PMID- 24909365
TI  - How much of NEWS could be measured by a machine, and would it work?

PMID- 24909366
TI  - Cognitive function and quality of life after successful resuscitation from
      cardiac arrest.
AB  - BACKGROUND: Studies on out-of-hospital cardiac arrest (OHCA) use overall
      performance category (OPC)/cerebral performance category (CPC) as outcome. We
      studied quality of life, neuro-cognitive functioning and independency in daily
      life of patients and strain of caregivers 6-12 months after cardiac arrest.
      METHODS: Two hundred and twenty patients (>18 year) who survived 6-12 months
      after OHCA and relatives were interviewed by telephone with validated
      questionnaires (Short-form Health Survey) (SF-12), Modified Rankin Scale (MRS),
      telephonic interview cognitive status (TICS) and Caregiver Strain Index (CSI) and
      compared with OPC and CPC at discharge. SF-12 of elderly (>=80 years) was
      compared to an open Dutch population of >=80 years. RESULTS: Of all patients, 45%
      had normal physical and 90% had normal mental SF-12. Eighty-one percent had a
      normal MRS (MRS<=2). Eighty-four percent had normal TICS. Compared to the
      reference population, elderly scored 40.5 on the mental physical [corrected] and
      53.2 on the physical mental [corrected] SF-12, while the reference population
      scored 38.1 (theta=0.20) and 54.4 (theta=-0.15), respectively, (n.s.) Of the
      patients with OPC<=2 and CPC<=2 at discharge 15% scored MRS 3-5 and 15% abnormal
      TICS at follow-up, respectively. Ninety-two percent of all patients gave their
      quality of life a value of >=6 (maximum 10). Patients treated with hypothermia
      scored on most health outcomes similar to those who did not need such treatment.
      Sixteen percent of caregivers experienced strain, correlating significantly with
      TICS of patients. CONCLUSION: The great majority of survivors have normal
      functioning and cognition 6-12 months after OHCA. Functional and neuro-cognitive
      telephonic tests 6-12 months after OHCA are simple and better reflect patients
      functioning at home than OPC/CPC at discharge.

PMID- 24909367
TI  - The effectiveness of avalanche airbags.
AB  - AIM: Asphyxia is the primary cause of death among avalanche victims. Avalanche
      airbags can lower mortality by directly reducing grade of burial, the single most
      important factor for survival. This study aims to provide an updated perspective
      on the effectiveness of this safety device. METHODS: A retrospective analysis of
      avalanche accidents involving at least one airbag user between 1994 and 2012 in
      Austria, Canada, France, Norway, Slovakia, Switzerland and the United States. A
      multivariate analysis was used to calculate adjusted absolute risk reduction and
      estimate the effectiveness of airbags on grade of burial and mortality. A
      univariate analysis was used to examine causes of non-deployment. RESULTS:
      Binomial linear regression models showed main effects for airbag use, avalanche
      size and injuries on critical burial, and for grade of burial, injuries and
      avalanche size on mortality. The adjusted risk of critical burial is 47% with non
      inflated airbags and 20% with inflated airbags. The adjusted mortality is 44% for
      critically buried victims and 3% for non-critically buried victims. The adjusted
      absolute mortality reduction for inflated airbags is -11 percentage points (22%
      to 11%; 95% confidence interval: -4 to -18 percentage points) and adjusted risk
      ratio is 0.51 (95% confidence interval: 0.29 to 0.72). Overall non-inflation rate
      is 20%, 60% of which is attributed to deployment failure by the user. CONCLUSION:
      Although the impact on survival is smaller than previously reported, these
      results confirm the effectiveness of airbags. Non-deployment remains the most
      considerable limitation to effectiveness. Development of standardized data
      collection protocols is encouraged to facilitate further research.

PMID- 24909369
TI  - Increased frequency of ILT2-expressing CD56(dim)CD16(+) NK cells correlates with
      disease severity of pulmonary tuberculosis.
AB  - The functional role of ILT2 in anti-tuberculosis immunity remains to be
      elucidated. In this study, we investigated expression and functions of ILT2 on NK
      cells during TB infection. The frequency of CD56(dim)CD16(+) NK cells that
      expressed ILT2 was significantly elevated in patients with active pulmonary TB as
      compared with tuberculin-positive healthy controls (p < 0.0001). TB patients with
      Mycobacterium tuberculosis smear/culture-positive result had significantly higher
      frequency of ILT2-expressing CD56(dim)CD16(+) NK cells than those with M.
      tuberculosis smear/culture-negative result (p < 0.0001), suggesting that ILT2
      expression on CD56(dim)CD16(+) NK cells correlated with disease severity of
      pulmonary TB. ILT2-expressing CD56(dim) NK cells had a functional defect, as
      evidenced by reduced expression of CD107a and IFN-gamma. Spontaneous apoptosis in
      ILT2(+)CD56(dim) NK cells was higher than in ILT2(-) cells. Blocking of ILT2
      signaling resulted in increased expression of CD107a on CD56(dim)CD16(+) NK
      cells. It is concluded that ILT2 has an inhibitory role on NK cells in patients
      with active TB. 

PMID- 24909370
TI  - Nutritional assessment and risk of malnutrition in hospitalised children in
      northern Italy.

PMID- 24909371
TI  - Obstetric conditions and the placental weight ratio.
AB  - INTRODUCTION: To elucidate how obstetric conditions are associated with atypical
      placental weight ratios (PWR)s in infants born: (a) >=37 weeks gestation; (b) at
      >=33 but <37 weeks gestation; and (c) <33 weeks gestation. METHODS: The study
      included all in-hospital singleton births in London, Ontario between June 1, 2006
      and March 31, 2011. PWR was assessed as <10th or >90th percentile by gestational
      age-specific local population standards. Multivariable analysis was carried out
      using multinomial logistic regression with blockwise variable entry in order of
      temporality. RESULTS: Baseline factors and maternal obstetric conditions
      associated with PWR <10th percentile were: increasing maternal height, overweight
      and obese body mass indexes (BMI), large for gestational age infants, smoking,
      and gestational diabetes. Obstetric factors associated with PWR >90th percentile
      were: underweight, overweight and obese BMIs, smoking, preeclampsia, placenta
      previa, and placental abruption. In particular, indicators of hypoxia and altered
      placental function were generally associated with elevated PWR at all gestations.
      DISCUSSION: An association between obstetric conditions associated with fetal
      hypoxia and PWR >=90th percentile was illustrated. CONCLUSIONS: The multivariable
      findings suggest that the PWR is similarly increased regardless of the etiology
      of the hypoxia.

PMID- 24909372
TI  - Statins alter the hepatobiliary transport of unconjugated and conjugated
      bilirubin in sandwich-cultured rat hepatocytes.
AB  - Several studies have reported that statins occasionally cause impairment of liver
      functions characterized by elevated serum bilirubin levels, which might be due to
      altered function of the multidrug resistance-associated proteins (Mrp2/3). We
      aimed to study the modulation of the hepatobiliary transport of bilirubin by four
      statin derivatives, atorvastatin, fluvastatin, pravastatin, and rosuvastatin in
      sandwich-cultured rat hepatocytes. All statins except pravastatin significantly
      inhibited the uptake of bilirubin. The biliary efflux of bilirubin conjugates was
      increased by pravastatin and rosuvastatin concentration dependently. Rosuvastatin
      stimulated not only the Mrp2 mediated biliary, but the Mrp3 mediated sinusoidal
      elimination, resulting in decreased intracellular bilirubin accumulation. The
      significantly induced Mrp2/3 protein levels (ranging from 1.5 to 1.8-fold)
      accounted for the elevated efflux. Cell polarization, the formation of biliary
      network was also significantly increased by fluvastatin, pravastatin and
      rosuvastatin (151%, 216% and 275% of the control, respectively). The simultaneous
      inhibition of the uptake and the stimulation of the sinusoidal and canalicular
      elimination may explain, at least in part, the clinical observation of elevated
      serum bilirubin levels. In conclusion, our results suggest that in spite of the
      elevated serum bilirubin levels, the altered Mrp2 and Mrp3 functions by statins
      is probably not associated with hepatotoxic effects. 

PMID- 24909373
TI  - Dermatopontin is a novel regulator of the CdCl2-induced decrease in claudin-11
      expression.
AB  - Cadmium (Cd) is a ubiquitous environmental heavy metal, which may be harmful to
      the reproductive functions through injury to the blood-testis barrier (BTB).
      However, the underlying mechanism of this adverse effect on the BTB remains
      uncharacterized. A preliminary study revealed that dermatopontin (DPT) expression
      was significantly increased in Cd chloride (CdCl2)-treated Sertoli cells in
      vitro, which suggested that an increase in DPT expression is crucial for CdCl2
      induced BTB damage. To explore this further, in the present study we initially
      determined that DPT is expressed in testis Sertoli cells. The treatment of cells
      with CdCl2 resulted in a significant increase in DPT expression and a parallel
      decrease in claudin-11 expression, both in vivo and in vitro. To confirm the
      relationship between DPT and claudin-11, a DPT-silenced 15P-1 Sertoli cell model
      was established. We determined that DPT silencing could partly reduce the CdCl2
      induced decrease in claudin-11 expression. Additionally, western blot analyses
      demonstrated that the p38 signaling pathway is involved in the effect of CdCl2 on
      DPT expression. In conclusion, the present study provides the first evidence that
      DPT may be a novel effector of CdCl2, highlighting the significant role of DPT in
      the regulation of claudin-11 expression. 

PMID- 24909375
TI  - Deep inspiration breath hold radiotherapy of lung cancer: the good, the bad and
      the ugly case.

PMID- 24909374
TI  - Intraocular involvement of T-cell lymphoma presenting as inflammatory glaucoma,
      neurotrophic keratopathy, and choroidal detachment.
AB  - Intraocular involvement of T-cell lymphoma is rare. We report a case presented
      with inflammatory glaucoma, neurotrophic keratopathy, and choroidal detachment.
      An 81-year-old man presented with unilateral high intraocular pressure and
      keratic precipitates. Polymerase chain reaction of the aqueous humor was negative
      for herpes simplex virus type 1 and 2, varicella zoster virus, and
      cytomegalovirus. Progressive pupil dilatation, cornea anesthesia with large
      epithelial defect, and choroidal detachment were noted in the following month.
      Diagnostic vitrectomy was then performed, and cytology of the vitreous suggested
      malignant lymphoma. Further systemic workup revealed ulcerative lesions in the
      stomach, and biopsy with special stains led to the diagnosis of peripheral T-cell
      lymphoma of the stomach with ocular involvement. Intraocular involvement of T
      cell lymphoma is very rare. Most typically, the skin, followed by the central
      nervous system, has the most frequently occurring concurrent systemic
      involvement. In fact, stomach involvement has not been reported. Most cases of
      intraocular lymphomas presented with vitritis and anterior uveitis, and elevated
      intraocular pressure was not commonly observed. A review of the literature
      indicates that a large corneal epithelium defect has been described only in a
      case of peripheral T-cell lymphoma with the involvement of sclera and oropharynx.
      Although very rare, inflammatory glaucoma, neurotrophic keratopathy, and
      choroidal detachment can be the initial presentation of intraocular involvement
      of T-cell lymphoma. 

PMID- 24909376
TI  - Audio-recorded information to patients considering participation in cancer
      clinical trials - a randomized study.
AB  - BACKGROUND: Patient information in cancer clinical trial is challenging. The
      value of audio-recording interventions for patients considering participating in
      clinical trials is unclear. The primary aim of this randomized study was to
      investigate effects of audio-recorded information on knowledge and understanding
      in patients considering participation in a clinical trial. MATERIAL AND METHODS:
      Patients scheduled for information about a phases 2 or 3 trial by one of the 13
      participating oncologists at the Department of Oncology during the study period
      (2008-2013) were eligible. The intervention consisted of an audio-recording on
      compact disc (CD) of the information at the medical consultation in which the
      patients were informed about a trial. Knowledge and understanding was measured by
      the questionnaire, Quality of Informed Consent. RESULTS: A total of 130 patients
      were randomized, 70% of the calculated sample size (n = 186). Sixty-seven
      patients were randomized to the intervention. In total, 101 patients (78%)
      completed questionnaires. No statistical significant differences were found
      between the groups with respect to knowledge and understanding. The level of
      knowledge was relatively high, with the exceptions of the risks associated with,
      and the unproven nature of, the trial. Overall, patients who declined
      participation scored statistically significant lower on knowledge. CONCLUSION:
      The present study was underpowered and the results should therefore be
      interpreted with caution. Still, 130 patients were included with a response rate
      of 78%. A CD including the oral information about a clinical trial did not show
      any effects on knowledge or understanding. However, the levels of knowledge were
      high, possible due to the high levels of education in the study group.
      Information on risks associated with the trial is still an area for improvement.

PMID- 24909377
TI  - Cancer mortality and other causes of death in users of geothermal hot water.
AB  - BACKGROUND: Residents of geothermal areas have increased incidence of non
      Hodgkin's lymphoma, breast, prostate, and kidney cancers. The aim was to study
      whether this is also reflected in cancer mortality among the population using
      geothermal hot water for space heating, washing, and showering. METHODS: The
      follow-up was from 1981 to 2009. Personal identifier of those 5-64 years of age
      was used in record linkage with nationwide death registry. Thus, vital and
      emigration status was ascertained. The exposed population was defined as
      inhabitants of communities with district heating generated from geothermal wells
      since 1972. Reference populations were inhabitants of other areas with different
      degrees of volcanic/geothermal activity. Hazard ratio (HR) and 95% confidence
      intervals (CI) were adjusted for age, gender, education, housing, reproductive
      factors and smoking habits. RESULTS: Among those using geothermal water, the HR
      for all causes of death was 0.98 (95% CI 0.91-1.05) as compared with cold
      reference area. The HR for breast cancer was 1.53 (1.04-2.24), prostate cancer
      1.74 (1.21-2.52), kidney cancer 1.78 (1.03-3.07), and for non-Hodgkin's lymphoma
      2.01 (1.05-3.38). HR for influenza was 3.36 (1.32-8.58) and for suicide 1.49
      (1.03-2.17). CONCLUSION: The significant excess mortality risk of breast and
      prostate cancers, and non-Hodgkin's lymphoma confirmed the results of similarly
      designed studies in Iceland on cancer incidence among populations from high
      temperature geothermal areas and users of geothermal hot water. The risk is not
      confined to cancers with good prognosis, but also concerns fatal cancers. Further
      studies are needed on the chemical and physical content of the water and the
      environment emissions in geothermal areas.

PMID- 24909378
TI  - Immunomodulating pectins from root bark, stem bark, and leaves of the Malian
      medicinal tree Terminalia macroptera, structure activity relations.
AB  - The root bark, stem bark, and leaves of Terminalia macroptera were sequentially
      extracted with ethanol, 50% ethanol-water, and 50 degrees C water using an
      accelerated solvent extractor (ASE). Six bioactive purified pectic polysaccharide
      fractions were obtained from the 50 degrees C crude water extracts after anion
      exchange chromatography and gel filtration. The root bark, stem bark, and leaves
      of T. macroptera were all good sources for fractions containing bioactive
      polysaccharides. The high molecular weight fraction 50WTRBH-I-I, being the most
      active fraction in the complement fixation test, has a highly ramified
      rhamnogalacturonan type I (RG-I) region with arabinogalactan type II (AG-II) side
      chains. The most abundant fractions from each plant part, 50WTRBH-II-I, 50WTSBH
      II-I, and 50WTLH-II-I, were chosen for pectinase degradation. The degradation
      with pectinase revealed that the main features of these fractions are that of
      pectic polysaccharides, with hairy regions (RG-I regions) and homogalacturonan
      regions. The activity of the fractions obtained after pectinase degradation and
      separation by gel filtration showed that the highest molecular weight fractions,
      50WTRBH-II-Ia, 50WTSBH-II-Ia, and 50WTLH-II-Ia, had higher complement fixation
      activity than their respective native fractions. These results suggest that the
      complement fixation activities of these pectins are expressed mainly by their
      ramified regions. 

PMID- 24909379
TI  - Structural studies and biosynthetic aspects of the O-antigen polysaccharide from
      Escherichia coli O42.
AB  - The structure of the O-antigen polysaccharide (PS) from Escherichia coli O42 has
      been investigated by NMR spectroscopy as the main method, which was complemented
      with sugar analysis, mass spectrometry, and analysis of biosynthetic information.
      The O-specific chain of the O-deacylated lipopolysaccharide (LPS-OH) consists of
      branched tetrasaccharide-glycerol repeating units joined by phosphodiester
      linkages. The lipid-free polysaccharide contains 0.8equiv of O-acetyl groups per
      repeating unit and has the following teichoic acid-like structure: Based on
      biosynthetic aspects, this should also be the biological repeating unit. This O
      antigen structure is remarkably similar to that of E. coli O28ac, differing only
      in the presence or absence, respectively, of a glucose residue at the branching
      point. The structural similarity explains the serological cross-reactivity
      observed between strains of these two serogroups, and also their almost identical
      O-antigen gene cluster sequences. 

PMID- 24909380
TI  - Transglycosylations employing recombinant alpha- and beta-galactosidases and
      novel donor substrates.
AB  - Recombinant alpha- and beta-galactosidases could be prepared in larger amounts
      for chemoenzymatic syntheses of glycosylated oligosaccharides relevant in
      nutrition approaches. alpha-Galactosidase RafA from Escherichia coli, another
      thermophilic alpha-galactosidase AgaB from Geobacillus stearothermophilus KVE39,
      and also a thermophilic beta-galactosidase BglT from Thermus thermophilus TH 125
      could be employed in alpha- and in beta-glycosylations, respectively. With model
      structures as well as sucrose, isomaltitol, and isomaltulose the stereo- and
      regiospecificities were studied. Further, a number of modified donor structures
      with structural variation and different leaving groups were synthesized,
      employed, and compared to classical donors for these transglycosylations. 

PMID- 24909381
TI  - Beta-lactamase and carbapenemase detection methods: an overview of recent
      patents.
AB  - Beta-lactam antibiotics constitute the agents most widely used against bacterial
      infections worldwide. Hence, the emergence and spread of beta-lactam hydrolyzing
      enzymes among pathogenic bacteria has proved to be one of the major medical
      issues especially when these enzymes inactivate carbapenems together with other
      beta-lactams. The prompt detection of beta-lactamases is important for
      therapeutic and epidemiological purposes therefore, various appropriate
      methodologies have been developed throughout the last decades. In the present
      overview, recent patents related to the detection of beta-lactamases and
      especially of carbapenemases are discussed. 

PMID- 24909382
TI  - Molecular neuroimaging of post-injury plasticity.
AB  - Nerve injury induces long-term changes in neuronal activity in the primary
      somatosensory cortex (S1), which has often been implicated as the origin of
      sensory dysfunction. However, the cellular mechanisms underlying this phenomenon
      remain unclear. C-fos is an immediate early gene, which has been shown to play an
      instrumental role in plasticity. By developing a new platform to image real-time
      changes in gene expression in vivo, we investigated whether injury modulates the
      levels of c-fos in layer V of S1, since previous studies have suggested that
      these neurons are particularly susceptible to injury. The yellow fluorescent
      protein, ZsYellow1, under the regulation of the c-fos promoter, was expressed
      throughout the rat brain. A fiber-based confocal microscope that enabled deep
      brain imaging was utilized, and local field potentials were collected
      simultaneously. In the weeks following limb denervation in adult rats (n=10),
      sensory stimulation of the intact limb induced significant increases in c-fos
      gene expression in cells located in S1, both contralateral (affected, 27.6+/-3
      cells) and ipsilateral (8.6+/-3 cells) to the injury, compared to controls (n=10,
      13.4+/-3 and 1.0+/-1, respectively, p value<0.05). Thus, we demonstrated that
      injury activates cellular mechanisms that are involved in reshaping neuronal
      connections, and this may translate to neurorehabilitative potential.

PMID- 24909383
TI  - Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac
      disease lesion plasma cells.
AB  - Coeliac disease (CD), an enteropathy caused by cereal gluten ingestion, is
      characterized by CD4(+) T cells recognizing deamidated gluten and by antibodies
      reactive to gluten or the self-antigen transglutaminase 2 (TG2). TG2-specific
      immunoglobulin A (IgA) of plasma cells (PCs) from CD lesions have limited somatic
      hypermutation (SHM). Here we report that gluten-specific IgA of lesion-resident
      PCs share this feature. Monoclonal antibodies were expression cloned from single
      PCs of patients either isolated from cultures with reactivity to complex
      deamidated gluten antigen or by sorting with gluten peptide tetramers. Typically,
      the antibodies bind gluten peptides related to T-cell epitopes and many have
      higher reactivity to deamidated peptides. There is restricted VH and VL
      combination and usage among the antibodies. Limited SHM suggests that a common
      factor governs the mutation level in PCs producing TG2- and gluten-specific IgA.
      The antibodies have potential use for diagnosis of CD and for detection of
      gluten. 

PMID- 24909384
TI  - Tube-weaning infants and children: a survey of Australian and international
      practice.
AB  - AIM: The aim of this study was to describe paediatric feeding-tube weaning
      practice in Australian children's hospitals and to compare this with practice in
      tube weaning programmes internationally. METHODS: A literature review regarding
      tube weaning practices was conducted to inform questionnaire design. Six
      Australian children's hospitals and six international paediatric service
      providers completed a written questionnaire. RESULTS: Four of six Australian
      children's hospitals surveyed reported that they have adopted informal paediatric
      tube weaning practices; four of six lacked clinical practice guidelines (CPGs),
      and five of six lacked a clearly defined case leadership. Practice varied
      substantially within and between these Australian feeding teams. By comparison,
      all six international feeding teams reported having developed formal CPGs. Five
      of six reported clearly defined case leadership with no more than three lead
      professionals overseeing cases and concordantly reported a high level of practice
      consistency within and between teams. CONCLUSIONS: The majority of Australian
      children's hospitals lack a formal CPG and clearly defined case leadership to
      guide tube weaning practices, and accordingly, there is considerable practice
      variation. This is in contrast to the situation in a select group of
      international centres. There is a need for further research to define best
      practice models and for Australian CPGs.

PMID- 24909385
TI  - Reptile-associated salmonellosis in Minnesota, 1996-2011.
AB  - Reptile-associated salmonellosis (RAS) occurs when Salmonella is transmitted from
      a reptile to a human. This study describes the epidemiology of RAS in Minnesota
      during 1996-2011. All Minnesotans with confirmed Salmonella infections are
      reported to the Minnesota Department of Health (MDH). Case patients are
      interviewed about illness characteristics and risk factors, including foods
      eaten, drinking and recreational water exposures, contact with ill people, and
      animal contact. Willing RAS case patients can submit stool from the reptile for
      culture. Serotype and pulsed-field gel electrophoresis (PFGE) subtype of
      Salmonella isolates from reptiles and case patients are compared. Of 8389
      sporadic (not associated with an outbreak) non-typhoidal salmonellosis case
      patients in Minnesotans during 1996-2011, 290 (3.5%) reported reptile exposure.
      The median age of case patients with reptile exposure was 11 years, 31% were
      under the age of 5 years and 67% were under the age of 20 years; 50% were female.
      The median illness duration was 8 days; 23% required hospitalization. The most
      commonly reported reptile exposures were lizard (47%), snake (20%), turtle (19%)
      and a combination of reptile types (14%). Eighty-four per cent of isolates from
      case patients who reported reptile exposure were Salmonella enterica subspecies
      I. The three most common serotypes were Typhimurium (15%), Enteritidis (7%) and
      subspecies IV serotypes (7%). Of 60 reptiles testing positive for Salmonella, 36
      (60%) yielded the same Salmonella serotype as the human isolate. Twenty-six of 27
      reptile isolates that were subtyped by PFGE were indistinguishable from the human
      isolate. Of these, 88% were subspecies I; the most common serotypes were
      Enteritidis (12%), Typhimurium (8%), and Bareilly (8%). RAS accounts for
      approximately 3.5% of salmonellosis cases in Minnesota, primarily affecting
      children. The majority of isolates from case patients and reptiles belonged to
      Salmonella subspecies I, suggesting that reptiles are a source of human infection
      with serotypes not traditionally considered to be reptile-associated.

PMID- 24909386
TI  - The prognostic value of preoperative serum levels of IL-12p40 and IL-23 for
      survival of patients with colorectal cancer.
AB  - Colorectal cancer (CRC) patients were previously shown to express a signature of
      cytokines that contribute to cancer pathogenesis and are detectable in serum. The
      aim of this study was to evaluate the potential clinical use of circulating
      cytokine measurements in CRC patients preoperatively as markers for disease
      outcome. The levels of cytokines IL-12p40 and IL-23 were assessed by ELISA in the
      sera of 91 patients with previously untreated CRC and then 5-year survival was
      determined using Kaplan-Meier analyses. The levels of circulating interleukin IL
      12p40 significantly decreased with the progression of CRC, whereas the levels of
      IL-23 remained with no significant differences between disease stages. None of
      the cytokine levels were influenced by age, gender and colon vs rectum
      localization. We found that preoperative serum concentration of IL-12p40 cytokine
      is a good prognostic marker for survival; as for IL-23 levels, we found no
      outcome prognostic value. In addition, 5-year survival confirmed that tumor
      grade, bowel wall invasion, lymph node and metastatic status have an impact on
      overall survival. In conclusion, we believe that our findings show clinical
      significance of the preoperative serum concentration for IL-12p40 and provide an
      additional prognostic biomarker for CRC survival.

PMID- 24909387
TI  - Photoresponsive and gas sensing field-effect transistors based on multilayer WS2
      nanoflakes.
AB  - The photoelectrical properties of multilayer WS2 nanoflakes including field
      effect, photosensitive and gas sensing are comprehensively and systematically
      studied. The transistors perform an n-type behavior with electron mobility of 12
      cm(2)/Vs and exhibit high photosensitive characteristics with response time (tau)
      of <20 ms, photo-responsivity (Rlambda) of 5.7 A/W and external quantum
      efficiency (EQE) of 1118%. In addition, charge transfer can appear between the
      multilayer WS2 nanoflakes and the physical-adsorbed gas molecules, greatly
      influencing the photoelectrical properties of our devices. The ethanol and NH3
      molecules can serve as electron donors to enhance the Rlambda and EQE
      significantly. Under the NH3 atmosphere, the maximum Rlambda and EQE can even
      reach 884 A/W and 1.7 * 10(5)%, respectively. This work demonstrates that
      multilayer WS2 nanoflakes possess important potential for applications in field
      effect transistors, highly sensitive photodetectors, and gas sensors, and it will
      open new way to develop two-dimensional (2D) WS2-based optoelectronics.

PMID- 24909388
TI  - Risk of adenomas with high-risk characteristics based on two previous
      colonoscopy.
AB  - BACKGROUND AND AIM: The recommended intervals between surveillance colonoscopies
      are based on the most recent examination findings. However, whether the two
      previous colonoscopies affect second surveillance colonoscopic findings is not
      established. The aim of this study is to estimate the risk of obtaining high-risk
      findings (HRF) on the next surveillance colonoscopy using the results of two
      previous colonoscopies, and to estimate the appropriate time interval for the
      next surveillance colonoscopy. METHODS: Among subjects who underwent screening
      colonoscopy during January 2002-December 2009, patients who underwent second
      surveillance colonoscopy before June 2012 were enrolled. "No adenoma" was defined
      as a hyperplastic polyp or no polyp, "low-risk findings (LRF)" as one or two
      small (< 1 cm) tubular adenomas, and "HRF" as advanced adenoma, cancer, or any
      sized multiple (>= 3) adenomas. RESULTS: Among enrolled 852 subjects, 65 (7.6%)
      had HRF at second surveillance colonoscopy. Multivariate analysis showed that HRF
      on second surveillance colonoscopy were associated with male and HRF on screening
      colonoscopy (all, P < 0.01). In subjects with LRF on first surveillance
      colonoscopy, HRF on the screening colonoscopy significantly affected the
      detection of HRF on second surveillance colonoscopy (P < 0.01). Patients with HRF
      on screening colonoscopy and LRF on the first surveillance colonoscopy had no
      different risk of HRF on second surveillance colonoscopy from those with HRF on
      first surveillance colonoscopy (P > 0.05). CONCLUSIONS: The HRF on second
      surveillance are significantly associated with previous two colonoscopic results.
      In patients with LRF on first surveillance, screening colonoscopic findings
      should be considered to determine the optimal surveillance interval.

PMID- 24909390
TI  - Antiplatelet activity of beta-blockers: new light on existing data.

PMID- 24909391
TI  - The rocking chair.

PMID- 24909389
TI  - Kin rejection: social signals, neural response and perceived distress during
      social exclusion.
AB  - Across species, kin bond together to promote survival. We sought to understand
      the dyadic effect of exclusion by kin (as opposed to non-kin strangers) on brain
      activity of the mother and her child and their subjective distress. To this end,
      we probed mother-child relationships with a computerized ball-toss game
      Cyberball. When excluded by one another, rather than by a stranger, both mothers
      and children exhibited a significantly pronounced frontal P2. Moreover, upon kin
      rejection versus stranger rejection, both mothers and children showed incremented
      left frontal positive slow waves for rejection events. Children reported more
      distress upon exclusion than their own mothers. Similar to past work, relatively
      augmented negative frontal slow wave activity predicted greater self-reported
      ostracism distress. This effect, generalized to the P2, was limited to mother- or
      child-rejection by kin, with comparable magnitude of effect across kin identity
      (mothers vs. children). For both mothers and children, the frontal P2 peak was
      significantly pronounced for kin rejection versus stranger rejection. Taken
      together, our results document the rapid categorization of social signals as kin
      relevant and the specificity of early and late neural markers for predicting felt
      ostracism. 

PMID- 24909392
TI  - WITHDRAWN: Refining the Role for Evacuation of Spontaneous Intracerebral
      Hematomas: Results of STICH II.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, DOI of original article:
      http://dx.doi.org/10.1016/j.wneu.2014.08.046. The duplicate article has therefore
      been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24909394
TI  - Observations on DSM-5 Mild Neurocognitive Disorder vs. its predecessor, Mild
      Cognitive Impairment.

PMID- 24909393
TI  - Comparison of polyetheretherketone and titanium cranioplasty after decompressive
      craniectomy.
AB  - OBJECTIVE: To characterize complication and failure rates and outcomes of
      patients who underwent cranioplasty with polyetheretherketone (PEEK) and titanium
      implants and to compare complication and failure rates between the 2 implants.
      METHODS: A retrospective cohort study of patients who underwent cranioplasty with
      PEEK patient-specific implant (PEEK Optima-LT) and preformed titanium mesh at the
      National Neuroscience Institute, Singapore, between January 2001 and February
      2012 was performed. Data related to initial decompressive craniectomy and
      cranioplasty, associated complications after cranioplasty, and indication for
      revision or removal of implants were collected. Cranioplasty failure was defined
      as revision or removal of a patient's implant. RESULTS: Overall complication
      rates for PEEK and titanium cranioplasty were 25.0% and 27.8%, respectively. The
      combined complication rate was 27.3%. A trend toward increase in exposed implant
      in titanium cranioplasty compared with PEEK cranioplasty was observed (P =
      0.074). There were 3 of 24 (12.5%) cranioplasty failures with PEEK, and 27 of 108
      (25%) cranioplasty failures with titanium (P = 0.129). Previous deep infection in
      patients after decompressive craniectomy was associated with cranioplasty
      complications (odds ratio, 23.3; confidence interval, 3.00-180.5; P = 0.003) and
      failure (odds ratio, 22.5; confidence interval, 2.82-179.0; P = 0.003).
      CONCLUSIONS: The findings from this study highlight that cranioplasty is
      associated with significant complications, including the necessity for
      reoperation. It is hoped that the information in this study will provide better
      understanding of the risks associated with PEEK and titanium cranioplasty and
      contribute to decision making by the clinician and patient.

PMID- 24909395
TI  - A five-year follow-up study of neurocognitive functioning in bipolar disorder.
AB  - OBJECTIVES: Cognitive dysfunction in bipolar disorder has been well-established
      in cross-sectional studies; however, there are few data regarding the
      longitudinal course of cognitive performance in bipolar disorder. The aim of this
      study was to examine the course of cognitive function in a sample of euthymic
      patients with bipolar disorder during a five-year follow-up period. METHODS:
      Eighty euthymic outpatients with a DSM-IV diagnosis of bipolar disorder and 40
      healthy control comparison subjects were neuropsychologically assessed at
      baseline (T1) and then at follow-up of five years (T2). A neurocognitive battery
      including the main cognitive domains of speed of processing, working memory,
      attention, verbal memory, visual memory, and executive function was used to
      evaluate cognitive performance. RESULTS: Repeated-measures multivariate analyses
      showed that progression of cognitive dysfunction in patients was not different to
      that of control subjects in any of the six cognitive domains examined. Only a
      measure from the verbal memory domain, delayed free recall, worsened more in
      patients with bipolar disorder. Additionally, it was found that clinical course
      during the follow-up period did not influence the course of cognitive
      dysfunction. CONCLUSIONS: Cognitive dysfunction that is characteristic of bipolar
      disorder is persistent and stable over time. Only dysfunction in verbal recall
      was found to show a progressive course that cannot be explained by clinical or
      treatment variables.

PMID- 24909396
TI  - Self-reported indicators of hypersexuality and its correlates in a female online
      sample.
AB  - INTRODUCTION: Hypersexual behavior has been a controversial and much disputed
      issue in the field of sexual medicine. However, only little attention has been
      paid to hypersexual behavior in women. Therefore, to date there is limited
      knowledge on the behavioral patterns of hypersexuality in women. AIMS: The
      purpose of the present study was to examine which sexual behavioral patterns are
      associated with self-reported indicators of hypersexuality in a female online
      sample. The second aim was to evaluate the association between hypersexuality and
      sexual risk behavior in women. METHODS: In total, 988 women participated in an
      online survey. Logistic regression analysis was conducted to examine the
      association between sexual behavioral patterns and hypersexuality. Furthermore,
      correlation analyses were calculated in order to identify the relationship
      between sexual risk behavior and hypersexuality. MAIN OUTCOME MEASURES:
      Indicators of hypersexual behavior were measured by the Hypersexual Behavior
      Inventory (HBI). In addition, current and present impersonal sexual activities
      were investigated. Sexual risk behavior was assessed using the Sexual Sensation
      Seeking Scale (SSSS). RESULTS: High masturbation frequency, number of sexual
      partners, and pornography use were associated with a higher degree of hypersexual
      behavior in women. Furthermore, the HBI total score was positively correlated to
      sexual risk behavior. CONCLUSION: The results of the current study do not support
      the idea of previous research that hypersexual women are typically engaged in
      more passive forms of sexual behavior. Rather female hypersexuality seems to be
      more characterized by impersonal sexual activity. An association between
      hypersexual behavior and sexual risk behavior was identified. The implications of
      these findings for potential prevention strategies and therapeutic interventions
      are discussed.

PMID- 24909397
TI  - Trichorhinophalangeal syndrome type II due to a novel 8q23.3-q24.12 deletion
      associated with imperforate hymen and vaginal stenosis.

PMID- 24909398
TI  - Interest of reflectance confocal microscopy for inflammatory oral mucosal
      diseases.

PMID- 24909399
TI  - Incidence of urethral stricture after bipolar transurethral resection of the
      prostate using TURis: results from a randomised trial.
AB  - OBJECTIVES: To assess whether bipolar transurethral resection of the prostate (B
      TURP) using the TURis system has a similar level of efficacy and safety to that
      of the traditional monopolar transurethral resection of the prostate (M-TURP),
      and to evaluate the impact of the TURis system on postoperative urethral
      stricture rates over a 36-month follow-up period. PATIENTS AND METHODS: A total
      of 136 patients with benign prostatic obstruction were randomised to undergo
      either B-TURP using the TURis system or conventional M-TURP, and were regularly
      followed for 36 months after surgery. The primary endpoint was safety, which
      included the long-term complication rates of postoperative urethral stricture.
      The secondary endpoint was the follow-up measurement of efficacy. RESULTS: In
      peri-operative findings, no patient in either treatment group presented with
      transurethral resection syndrome, and the decline in levels of haemoglobin and
      hematocrit were similar. The mean operation time was significantly extended in
      the TURis treatment group compared with the M-TURP group (79.5 vs 68.6 min; P =
      0.032) and postoperative clot retention was more likely to be seen after M-TURP
      (P = 0.044). Similar efficacy findings were maintained throughout 36 months, but
      a significant difference in postoperative urethral stricture rates between groups
      was detected (6.6% in M-TURP vs 19.0% in TURis; P = 0.022). After stratifying
      patients according to prostate volume, there was no significant difference
      between the two treatment groups with regard to urethral stricture rates in
      patients with a prostate volume <= 70 mL (3.8% in M-TURP vs 3.8% in TURis), but
      in the TURis group there was a significantly higher urethral stricture rate
      compared with the M-TURP group in patients with a prostate volume >70 mL (20% in
      TURis vs 2.2% in M-TURP; P = 0.012). Furthermore, the mean operation time for
      TURis was significantly longer than for M-TURP for the subgroup of patients with
      a prostate volume > 70 mL (99.6 vs 77.2 min; P = 0.011), but not for the subgroup
      of patients with a prostate volume <= 70 mL. CONCLUSION: The TURis system seems
      to be as efficacious and safe as conventional M-TURP except that there was a
      higher incidence of urethral stricture in patients with larger preoperative
      prostate volumes.

PMID- 24909400
TI  - Negative impact of laws regarding biosecurity and bioterrorism on real diseases.
AB  - Research on highly pathogenic microorganisms in biosafety level 3 and 4
      laboratories is very important for human public health, as it provides
      opportunities for the development of vaccines and novel therapeutics as well as
      diagnostic methods to prevent epidemics. However, in recent years, after the
      anthrax and World Trade Center attacks in 2001 in the USA, the threat of
      bioterrorism has grown for both the public and the authorities. As a result,
      technical and physical containment measures and biosafety and biosecurity
      practices have been implemented in laboratories handling these dangerous
      pathogens. Working with selected biological agents and toxins is now highly
      regulated, owing to their potential to pose a threat to public health and safety,
      despite the fact that the anthrax attack was found to be the result of a lack of
      security at a US Army laboratory. Thus, these added regulations have been
      associated with a large amount of fruitless investment. Herein, we describe the
      limitations of research in these facilities, and the multiple consequences of the
      increased regulations. These limitations have seriously negatively impacted on
      the number of collaborations, the size of research projects, and, more generally,
      scientific research on microbial pathogens. Clearly, the actual number of known
      victims and fatalities caused by the intentional use of microorganisms has been
      negligible as compared with those caused by naturally acquired human infections.

PMID- 24909401
TI  - Lack of myostatin reduces MyoD induced myogenic potential of primary muscle
      fibroblasts.
AB  - Conversion of skin fibroblasts into myoblasts by transducing the cells with
      myogenic master regulator MyoD has been in practice for more than two decades.
      The purpose of such conversion is due to scarcity of muscle biopsies during
      muscle wasting, hence conversion of fibroblasts to myogenic lineage from various
      genetic backgrounds offers a great alternative for cell therapies. Here, we have
      investigated if eliminating Myostatin, a potent negative regulator of myogenesis,
      could improve the myogenic conversion of fibroblasts. In the present study, we
      have isolated primary muscle fibroblasts from the skeletal muscles of wild-type
      (WT) and myostatin null (Mstn(-/-)) mice and transduced the muscle fibroblasts
      with MyoD using adenoviral, lentiviral transduction, and electroporation methods.
      In contrast to what we predicted, it is only in WT muscle fibroblasts we detected
      significant ectopic expression of MyoD, and myogenic conversion. Muscle
      fibroblasts from Mstn(-/-) genotype failed to take up as much MyoD using the
      three methods and, therefore, failed to form myotubes. The aforesaid condition of
      greater MyoD uptake by WT muscle fibroblasts was attributed to the presence of
      adenoviral receptors, which facilitated adenoviral transduction. However, in
      Mstn(-/-) fibroblasts we detected negligible levels of adenovirus receptors.
      Moreover, we also detected significantly higher levels of MyoD antagonists, c
      Fos, c-Jun, and cyclin D1 in Mstn(-/-) muscle fibroblasts. Taken together, our
      results demonstrate that lack of myostatin reduces myogenic potential of muscle
      fibroblasts by inhibiting MyoD function.

PMID- 24909402
TI  - Identification of ultrafast relaxation processes as a major reason for
      inefficient exciton diffusion in perylene-based organic semiconductors.
AB  - The exciton diffusion length (LD) is a key parameter for the efficiency of
      organic optoelectronic devices. Its limitation to the nm length scale causes the
      need of complex bulk-heterojunction solar cells incorporating difficulties in
      long-term stability and reproducibility. A comprehensive model providing an
      atomistic understanding of processes that limit exciton trasport is therefore
      highly desirable and will be proposed here for perylene-based materials. Our
      model is based on simulations with a hybrid approach which combines high-level ab
      initio computations for the part of the system directly involved in the described
      processes with a force field to include environmental effects. The adequacy of
      the model is shown by detailed comparison with available experimental results.
      The model indicates that the short exciton diffusion lengths of alpha-perylene
      tetracarboxylicdianhydride (PTCDA) are due to ultrafast relaxation processes of
      the optical excitation via intermolecular motions leading to a state from which
      further exciton diffusion is hampered. As the efficiency of this mechanism
      depends strongly on molecular arrangement and environment, the model explains the
      strong dependence of LD on the morphology of the materials, for example, the
      differences between alpha-PTCDA and diindenoperylene. Our findings indicate how
      relaxation processes can be diminished in perylene-based materials. This model
      can be generalized to other organic compounds. 

PMID- 24909403
TI  - Follicular variant of papillary thyroid carcinoma with B-type Raf(V600E) showing
      higher frequency of suspicious sonographic features and multifocality.
AB  - BACKGROUND: The purpose of this study was to investigate the correlation between
      B-type Raf (BRAF) kinase mutation and clinicopathological features of follicular
      variant of papillary thyroid carcinoma (PTC). METHODS: Eighty-four patients with
      pathologically confirmed follicular variant of PTC, who underwent a preoperative
      BRAF(V600E) study, were analyzed. Clinicopathological parameters and
      ultrasonographic features were compared between the BRAF(V600E) -positive and
      negative groups. RESULTS: A total of 41.7% of the patients showed BRAF(V600E) .
      The BRAF(V600E) -positive group showed the smaller tumor size (7.3 +/- 3.6 mm vs
      10.7 +/- 8.9 mm; p = .018) and the more frequent multifocality (25.7% vs 8.2%; p
      = .028). Follicular variant of PTC with BRAF(V600E) showed suspicious
      ultrasonographic features (88.6% vs 57.1%; p = .002) more frequently. BRAF(V600E)
      positivity is associated with multifocality after adjusting for age, sex, the
      presence of suspicious ultrasonographic features, pathological tumor size, and
      thyrotropin level. CONCLUSION: BRAF(V600E) was correlated with smaller tumor size
      and suspicious ultrasonographic features in follicular variant of PTC.
      BRAF(V600E) was a significant parameter for predicting multifocality of
      follicular variant of PTC.

PMID- 24909404
TI  - Passive immunity with multi-serotype heat-killed Shigellae in neonatal mice.
AB  - The short- and long-term passive protective efficacy of a mixture of heat-killed
      cells of six serogroups/serotypes of Shigella strains (Shigella dysenteriae 1, S.
      flexneri 2a, S. flexneri 3a, S. flexneri 6, S. boydii 4, and S. sonnei) were
      studied in neonatal mice. Neonatal mice from immunized dams exhibited significant
      short- and long-term passive protection against individual challenge by each of
      the six Shigella strains. High IgG and IgA titers against the lipopolysaccharide
      from each of the six Shigella strains were observed in sera from immunized dams. 

PMID- 24909405
TI  - On the design of supramolecular assemblies made of peptides and lipid bilayers.
AB  - Peptides confer interesting properties to materials, supramolecular assemblies
      and to lipid membranes and are used in analytical devices or within delivery
      vehicles. Their relative ease of production combined with a high degree of
      versatility make them attractive candidates to design new such products. Here, we
      review and demonstrate how CD- and solid-state NMR spectroscopic approaches can
      be used to follow the reconstitution of peptides into membranes and to describe
      some of their fundamental characteristics. Whereas CD spectroscopy is used to
      monitor secondary structure in different solvent systems and thereby aggregation
      properties of the highly hydrophobic domain of p24, a protein involved in vesicle
      trafficking, solid-state NMR spectroscopy was used to deduce structural
      information and the membrane topology of a variety of peptide sequences found in
      nature or designed. (15)N chemical shift solid-state NMR spectroscopy indicates
      that the hydrophobic domain of p24 as well as a designed sequence of 19
      hydrophobic amino acid residues adopt transmembrane alignments in
      phosphatidylcholine membranes. In contrast, the amphipathic antimicrobial peptide
      magainin 2 and the designed sequence LK15 align parallel to the bilayer surface.
      Additional angular information is obtained from deuterium solid-state NMR spectra
      of peptide sites labelled with (2)H3-alanine, whereas (31)P and (2)H solid-state
      NMR spectra of the lipids furnish valuable information on the macroscopic order
      and phase properties of the lipid matrix. Using these approaches, peptides and
      reconstitution protocols can be elaborated in a rational manner, and the analysis
      of a great number of peptide sequences is reviewed. Finally, a number of
      polypeptides with membrane topologies that are sensitive to a variety of
      environmental conditions such as pH, lipid composition and peptide-to-lipid ratio
      will be presented.

PMID- 24909406
TI  - Comparative proteome profiling of bovine and human Staphylococcus epidermidis
      strains for screening specifically expressed virulence and adaptation proteins.
AB  - The present study reports a comparative proteome cataloging of a bovine mastitis
      and a human-associated Staphylococcus epidermidis strain with a specific focus on
      surfome (cell-wall bound and extracellular) proteins. Protein identification by
      1DE coupled with LC-MS/MS analyses resulted in 1400 and 1287 proteins from the
      bovine (PM221) and human (ATCC12228) strains, respectively, covering over 50% of
      all predicted and more than 30% of all predicted surfome proteins in both
      strains. Comparison of the identification results suggests elevated levels of
      proteins involved in adherence, biofilm formation, signal transduction, house
      keeping functions, and immune evasion in PM221, whereas ATCC12228 was more
      effective in expressing host defense evasion proteases, skin adaptation lipases,
      hemagglutination, and heavy-metal resistance proteins. Phenotypic analyses showed
      that only PM221 displays protein- and DNA-mediated adherent growth, and that
      PM221 was more efficient in cleaving tributyrin, a natural compound of milk fat
      under low CO2 conditions. These findings are in line with the identification data
      and suggest that distinct expression of lipases and adhesive surfome proteins
      could lead to the observed phenotypes. This study is the first extensive survey
      of S. epidermidis proteomes to date, providing several protein candidates to be
      examined for their roles in adaptation and virulence in vivo. All MS data have
      been deposited in the ProteomeXchange with identifier PXD000404
      (http://proteomecentral.proteomexchange.org/dataset/PXD000404). 

PMID- 24909408
TI  - Improving adherence to antiretroviral treatment in Uganda with a low-resource
      facility-based intervention.
AB  - OBJECTIVE: To assess the effects of facility-based interventions using existing
      resources to improve overall patient attendance and adherence to antiretroviral
      therapy (ART) at ART-providing facilities in Uganda. METHODS: This was an
      interventional study which tracked attendance and treatment adherence of two
      distinct cohorts: experienced patients who had been on treatment for at least 12
      months prior to the intervention and patients newly initiated on ART before or
      during the intervention. The interventions included instituting appointment
      system, fast-tracking, and giving longer prescriptions to experienced stable
      patients. Mixed-effects models were used to examine intervention effects on the
      experienced patients, while Cox proportional hazards models were used to
      determine the intervention effects on time until newly treated patients
      experienced gaps in medication availability. RESULTS: In all, 1481 patients'
      files were selected for follow-up from six facilities--720 into the experienced
      cohort, and 761 into the newly treated cohort. Among patients in the experienced
      cohort, the interventions were associated with a significant reduction from 24.4
      to 20.3% of missed appointments (adjusted odds ratio (AOR): 0.67; 95% confidence
      interval (CI): 0.59-0.77); a significant decrease from 20.2 to 18.4% in the
      medication gaps of three or more days (AOR: 0.69; 95% CI: 0.60-0.79); and a
      significant increase from 4.3 to 9.3% in the proportion of patients receiving
      more than 30 days of dispensed medication (AOR: 2.35; 95% CI: 1.91-2.89). Among
      newly treated patients, the interventions were associated with significant
      reductions of 44% (adjusted hazard rate (AHR): 0.56, 95% CI: 0.42-0.74) and 38%
      (AHR: 0.62; 95% CI: 0.45-0.85) in the hazards of experiencing a medication gap of
      7 and 14 days or more, respectively. CONCLUSIONS: Patients' adherence was
      improved with low-cost and easily implemented interventions using existing health
      facilities' resources. We recommend that such interventions be considered for
      scale-up at national levels as measures to improve clinic attendance and ART
      adherence among patients in Uganda and other low-resource settings in sub-Saharan
      Africa.

PMID- 24909407
TI  - The first 500 days of life: policies to support maternal nutrition.
AB  - BACKGROUND: From conception to 6 months of age, an infant is entirely dependent
      for its nutrition on the mother: via the placenta and then ideally via exclusive
      breastfeeding. This period of 15 months--about 500 days--is the most important
      and vulnerable in a child's life: it must be protected through policies
      supporting maternal nutrition and health. Those addressing nutritional status are
      discussed here. OBJECTIVE AND DESIGN: This paper aims to summarize research on
      policies and programs to protect women's nutrition in order to improve birth
      outcomes in low- and middle-income countries, based on studies of efficacy from
      the literature, and on effectiveness, globally and in selected countries
      involving in-depth data collection in communities in Ethiopia, India and Northern
      Nigeria. Results of this research have been published in the academic literature
      (more than 30 papers). The conclusions now need to be advocated to policy-makers.
      RESULTS: The priority problems addressed are: intrauterine growth restriction
      (IUGR), women's anemia, thinness, and stunting. The priority interventions that
      need to be widely expanded for women before and during pregnancy, are:
      supplementation with iron-folic acid or multiple micronutrients; expanding
      coverage of iodine fortification of salt particularly to remote areas and the
      poorest populations; targeted provision of balanced protein energy supplements
      when significant resources are available; reducing teenage pregnancies;
      increasing interpregnancy intervals through family planning programs; and
      building on conditional cash transfer programs, both to provide resources and as
      a platform for public education. All these have known efficacy but are of
      inadequate coverage and resourcing. The next steps are to overcome barriers to
      wide implementation, without which targets for maternal and child health and
      nutrition (e.g. by WHO) are unlikely to be met, especially in the poorest
      countries. CONCLUSIONS: This agenda requires policy decisions both at Ministry
      and donor levels, and throughout the administrative system. Evidence-based
      interventions are established as a basis for these decisions, there are clear
      advocacy messages, and there are no scientific reasons for delay.

PMID- 24909409
TI  - Causes of death among undocumented migrants in Sweden, 1997-2010.
AB  - BACKGROUND: Undocumented migrants are one of the most vulnerable groups in
      Swedish society, where they generally suffer from poor health and limited health
      care access. Due to their irregular status, such migrants are an under-researched
      group and are not included in the country's Cause of Death Register (CDR).
      OBJECTIVE: To determine the causes of death among undocumented migrants in Sweden
      and to ascertain whether there are patterns in causes of death that differ
      between residents and undocumented migrants. DESIGN: This is a cross-sectional
      study of death certificates issued from 1997 to 2010 but never included in the
      CDR from which we established our study sample of undocumented migrants. As age
      adjustments could not be performed due to lack of data, comparisons between
      residents and undocumented migrants were made at specific age intervals, based on
      the study sample's mean age at death+/-a half standard deviation. RESULTS: Out of
      7,925 individuals surveyed, 860 were classified as likely to have been
      undocumented migrants. External causes (49.8%) were the most frequent cause of
      death, followed by circulatory system diseases, and then neoplasms. Undocumented
      migrants had a statistically significant increased risk of dying from external
      causes (odds ratio [OR] 3.57, 95% confidence interval [CI]: 2.83-4.52) and
      circulatory system diseases (OR 2.20, 95% CI: 1.73-2.82) compared to residents,
      and a lower risk of dying from neoplasms (OR 0.07, 95% CI: 0.04-0.14).
      CONCLUSIONS: We believe our study is the first to determine national figures on
      causes of death of undocumented migrants. We found inequity in health as
      substantial differences in causes of death between undocumented migrants and
      residents were seen. Legal ambiguities regarding health care provision must be
      addressed if equity in health is to be achieved in a country otherwise known for
      its universal health coverage.

PMID- 24909410
TI  - MS Amanda, a universal identification algorithm optimized for high accuracy
      tandem mass spectra.
AB  - Today's highly accurate spectra provided by modern tandem mass spectrometers
      offer considerable advantages for the analysis of proteomic samples of increased
      complexity. Among other factors, the quantity of reliably identified peptides is
      considerably influenced by the peptide identification algorithm. While most
      widely used search engines were developed when high-resolution mass spectrometry
      data were not readily available for fragment ion masses, we have designed a
      scoring algorithm particularly suitable for high mass accuracy. Our algorithm, MS
      Amanda, is generally applicable to HCD, ETD, and CID fragmentation type data. The
      algorithm confidently explains more spectra at the same false discovery rate than
      Mascot or SEQUEST on examined high mass accuracy data sets, with excellent
      overlap and identical peptide sequence identification for most spectra also
      explained by Mascot or SEQUEST. MS Amanda, available at
      http://ms.imp.ac.at/?goto=msamanda , is provided free of charge both as
      standalone version for integration into custom workflows and as a plugin for the
      Proteome Discoverer platform. 

PMID- 24909412
TI  - Physical comorbidities affect physical activity in chronic obstructive pulmonary
      disease: a prospective cohort study.
AB  - BACKGROUND AND OBJECTIVE: The prevalence of physical comorbidities such as
      obesity, musculoskeletal or neurological conditions in people with chronic
      obstructive pulmonary disease (COPD) is high, yet little is known about the
      impact of these physical comorbidities on physical activity. The primary aim of
      the study was to compare the physical activity levels of people with COPD with
      physical comorbidities (COPD + PC) to people with COPD without physical
      comorbidities (COPD) and healthy age-matched volunteers (control group). METHODS:
      Twenty-five people with COPD + PC (mean (standard deviation (SD)) age 73 (11)
      years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II
      IV), 25 people with COPD (70 (8) years, GOLD stage II-IV) and 25 controls (70 (7)
      years) wore the SenseWear Pro3 Armband for 7 days. RESULTS: Engagement in light
      intensity physical activity (1.5-3.0 metabolic equivalents (MET)) (140 (76)
      minutes per day (min/day)) and moderate intensity physical activity (3.0-6.0 MET)
      (25 (35) min/day) in the COPD + PC group was significantly reduced compared with
      the COPD (231 (76) and 104 (106), respectively) and control group (259 (75) and
      114 (57), respectively). In the 16 daytime hours between 6 am and 10 pm, people
      with COPD + PC spent a mean (SD) of 771 (98) min/day engaged in sedentary
      behaviour (<1.5 MET). This was significantly greater than the group with COPD
      (603 (148) min/day) and the control group (567 (76) min/day) (P < 0.001).
      CONCLUSIONS: People with COPD + PC had significantly lower daily physical
      activity levels compared with people with COPD without physical comorbidities and
      healthy people.

PMID- 24909411
TI  - Transient alpha-helices in the disordered RPEL motifs of the serum response
      factor coactivator MKL1.
AB  - The megakaryoblastic leukemia 1 (MKL1) protein functions as a transcriptional
      coactivator of the serum response factor. MKL1 has three RPEL motifs (RPEL1,
      RPEL2, and RPEL3) in its N-terminal region. MKL1 binds to monomeric G-actin
      through RPEL motifs, and the dissociation of MKL1 from G-actin promotes the
      translocation of MKL1 to the nucleus. Although structural data are available for
      RPEL motifs of MKL1 in complex with G-actin, the structural characteristics of
      RPEL motifs in the free state have been poorly defined. Here we characterized the
      structures of free RPEL motifs using NMR and CD spectroscopy. NMR and CD
      measurements showed that free RPEL motifs are largely unstructured in solution.
      However, NMR analysis identified transient alpha-helices in the regions where
      helices alpha1 and alpha2 are induced upon binding to G-actin. Proline
      mutagenesis showed that the transient alpha-helices are locally formed without
      helix-helix interactions. The helix content is higher in the order of RPEL1,
      RPEL2, and RPEL3. The amount of preformed structure may correlate with the
      binding affinity between the intrinsically disordered protein and its target
      molecule. 

PMID- 24909413
TI  - Safety and efficacy of deep sedation as compared to general anaesthesia in
      percutaneous mitral valve repair using the MitraClip system.
AB  - OBJECTIVE: To characterize the safety and efficacy of deep sedation (DS) as
      compared to general anaesthesia (GA) in percutaneous mitral valve repair (PMVR)
      using the MitraClip system. BACKGROUND: PMVR with the MitraClip system has
      emerged as a therapeutic alternative to surgical valve repair in high-risk
      patients. The PMVR procedure is typically performed under GA. Due to their high
      surgical risk, avoidance of GA in many of those patients would be desirable.
      METHODS: In an open-label observational study 21 patients with severe mitral
      regurgitation were randomized to either GA or DS using propofol. Primary
      endpoints of this comparison were related to safety with rate of conversion from
      DS to GA, bleeding, aspiration, and pneumonia. Secondary endpoints were related
      to efficacy with procedural, in-hospital, and mid-term outcome at 1 month.
      RESULTS: All clips have been implanted successfully in both groups. No conversion
      from DS to GA was necessary. Four patients undergoing GA suffered from upper
      respiratory tract infections and two from peripheral vascular complications
      during placement of central venous catheter for GA. Short- and mid-term efficacy
      were comparable in both groups with a reduced hospital stay in the DS group.
      CONCLUSION: PVMR in high-risk patients performed under DS is as safe and
      effective as with GA, preventing complications related to GA and shortening
      hospital stay.

PMID- 24909414
TI  - Thermoresponsive copolymer decorated surface enables controlling the adsorption
      of a target protein in plasma.
AB  - The control of protein/surface interactions by external stimuli is often required
      in bioapplications such as bioseparation and biosensors. Although regulation of
      protein adsorption has been achieved on the surfaces modified with stimuli
      responsive polymers, controlled protein adsorption is still challenging for a
      target protein in a multiprotein system. The present study developed a concept of
      surface design for the controlled adsorption of a specific protein from plasma by
      combining a thermoresponsive polymer with an affinity ligand on the surface. In
      this regard, a polyurethane (PU) surface was modified with the copolymer of N
      isopropylacrylamide (NIPAAm) and a epsilon-lysine-containing monomer (LysMA).
      epsilon-Lysine is a specific ligand for plasminogen that was used as the model
      "target protein" in this study. The PU-P(NIPAAm-co-Lys) surfaces exhibited
      distinct thermoresponsivity of plasminogen adsorption from plasma with a larger
      quantity adsorbed at 37  degrees C than at 23  degrees C. By contrast, the
      surfaces showed a low level of adsorption for other plasma proteins at both
      temperatures. In addition, plasminogen adsorbed on a PU-P(NIPAAm-co-Lys) surface
      could be partly desorbed by lowering the temperature, and the activity of
      plasminogen adsorbed was well preserved. We believe that the concept developed in
      this study can be extended to other proteins by combining PNIPAAm and specific
      ligands with affinities for the proteins of interest. 

PMID- 24909415
TI  - Chiral separation of cathinone and amphetamine derivatives by HPLC/UV using
      sulfated beta-cyclodextrin as chiral mobile phase additive.
AB  - In the last years the identification of new legal and illegal highs has become a
      huge challenge for the police and prosecution authorities. In an analytical
      context, only a few analytical methods are available to identify these new
      substances. Moreover, many of these recreational drugs are chiral and it is
      supposed that the enantiomers differ in their pharmacological potency. Since
      nonenantioselective synthesis is easier and cheaper, they are mainly sold as
      racemic mixtures. The goal of this research work was to develop an inexpensive
      method for the chiral separation of cathinones and amphetamines. This should help
      to discover if the substances are sold as racemic mixtures and give further
      information about their quality as well as their origin. Chiral separation of a
      set of 6 amphetamine and 25 cathinone derivatives, mainly purchased from various
      Internet shops, is presented. A LiChrospher 100 RP-18e, 250 x 4 mm, 5 um served
      as the stationary phase. The chiral mobile phase consisted of methanol, water,
      and sulfated beta-cyclodextrin. Measurements were performed under isocratic
      conditions in reversed phase mode using UV detection. Four model compounds of the
      two substance classes were used to optimize the mobile phase. Under final
      conditions (methanol:water 2.5:97.5 + 2% sulfated beta-cyclodextrin) enantiomers
      of amphetamine and five derivatives were baseline separated within 23 min. In
      all, 17 cathinones were completely or partially chirally separated. However, as
      only 3 of 25 cathinones were baseline resolved, the application of this method is
      limited for cathinone analogs. Additionally, the results were compared with an RP
      8e column.

PMID- 24909417
TI  - Potentials of polymeric nanoparticle as drug carrier for cancer therapy: with a
      special reference to pharmacokinetic parameters.
AB  - Nanomaterials have made a significant impact on cancer therapeutics and an
      emergence of polymeric nanoparticle provides a unique platform for delivery of
      drug molecules of diverse nature. Nanoparticles can be targeted at the tumor
      cells due to enhanced permeability and retention effect. Moreover, nanoparticles
      can be grafted by various ligands on their surface to target the specific
      receptors overexpressed by cancer cells or angiogenic endothelial cells. These
      approaches ultimately result in longer circulation half-lives, improved drug
      pharmacokinetics, reduced side effects of therapeutically active substances and
      overcoming cancer chemo-resistance thereby enhancing the therapeutic efficacy of
      the treatment. This review article summarizes the recent efforts in cancer
      nanochemotherapeutics using polymeric nanoparticles with a special reference to
      their pharmacokinetic and biodistribution profiles, their role in reversing
      multidrug resistance in cancer and strategies of tumor targeting with them, along
      with the challenges in the field. 

PMID- 24909416
TI  - The microtubule destabilizing protein stathmin controls the transition from
      dividing neuronal precursors to postmitotic neurons during adult hippocampal
      neurogenesis.
AB  - The hippocampus is one of the two areas in the mammalian brain where adult
      neurogenesis occurs. Adult neurogenesis is well known to be involved in
      hippocampal physiological functions as well as pathophysiological conditions.
      Microtubules (MTs), providing intracellular transport, stability, and
      transmitting force, are indispensable for neurogenesis by facilitating cell
      division, migration, growth, and differentiation. Although there are several
      examples of MT-stabilizing proteins regulating different aspects of adult
      neurogenesis, relatively little is known about the function of MT-destabilizing
      proteins. Stathmin is such a MT-destabilizing protein largely restricted to the
      CNS, and in contrast to its developmental family members, stathmin is also
      expressed at significant levels in the adult brain, notably in areas involved in
      adult neurogenesis. Here, we show an important role for stathmin during adult
      neurogenesis in the subgranular zone of the mouse hippocampus. After carefully
      mapping stathmin expression in the adult dentate gyrus (DG), we investigated its
      role in hippocampal neurogenesis making use of stathmin knockout mice. Although
      hippocampus development appears normal in these animals, different aspects of
      adult neurogenesis are affected. First, the number of proliferating Ki-67+ cells
      is decreased in stathmin knockout mice, as well as the expression of the immature
      markers Nestin and PSA-NCAM. However, newborn cells that do survive express more
      frequently the adult marker NeuN and have a more mature morphology. Furthermore,
      our data suggest that migration in the DG might be affected. We propose a model
      in which stathmin controls the transition from neuronal precursors to early
      postmitotic neurons.

PMID- 24909418
TI  - Gold nanoparticle-based drug delivery platform for antineoplastic chemotherapy.
AB  - Gold nanoparticles (AuNPs) have demonstrated increasingly wide applications in
      drug delivery due to their unique physicochemical and optical properties as well
      as low toxicity. Compared to the organic nanocarriers for therapeutic agents,
      AuNPs have shown superior performance as drug delivery vectors, including the
      inert nature, well-developed synthesis strategies, tunable size, and flexible and
      easy surface modification with various chemical and biological molecules. In this
      review, we emphasize on the applications of AuNPs in the aspect of improving
      pharmaceutical property and therapeutic efficacy of drugs, especially those
      covalently and noncovalently connected to the surface of AuNPs. Acting as a solid
      core to link drugs and their derivatives, AuNPs provide the nano-prodrug system
      with compressed size, high loading efficiency, three-dimension structure, and
      enhanced cellular uptake capability. With the intensive and systematical
      investigation of the drug-connected AuNPs, several important issues will become
      the hot but emergent topics for future research in this field, such as the
      toxicity in live human subjects, ultimate destination, and possible pathways and
      mechanisms for their absorption, circulation, distribution, metabolism, and
      excretion. 

PMID- 24909420
TI  - Research/review: Structure and linkage disequilibrium analysis of adamantane
      resistant mutations in influenza virus m2 proton channel.
AB  - The M2 proton channel is translated by the M gene segment of influenza viruses,
      and has been adopted as an attractive target for influenza A viruses, on which a
      series of adamantane-based drugs act. However, recently epidemic influenza
      viruses have had strong resistant effects against the adamantane-based drugs. In
      this paper, we combined evolutionary analyses, linkage disequilibrium as well as
      molecular dynamics simulations to explore the drug resistance of the M2 proton
      channel, with an aim of providing an in-depth understanding of the resistant
      mechanism for adamantane-based drugs. We collected 2746 coding sequences for
      swine, avian, and human M2 proteins. After evolutionary and linkage
      disequilibrium analyses, we found that the some residues in the C-terminal were
      associated with the famed resistant mutation S31N. Subsequently, we constructed
      the 3D structures of the swine, avian as well as human M2 channel, and performed
      MD simulations on these channels with a typical adamantane-based drug
      rimantadine. From the simulation trajectories, we found that the resistance
      against the adamantane-based drugs for the M2 channel from 2009 A(H1N1) viruses
      was derived from the structural allostery in the transmembrane and C-terminal
      regions. The helices in the transmembrane region were irregular in formation and
      employed larger distances between the adjacent 2 helices, which can weaken the
      interactions between the adjacent 2 helices and destabilize the helix-helix
      assembly, resulting in a comparatively loosely structure. The helices in the C
      terminal region show a disordered configuration, giving chances for solvent
      molecules to enter into the channel pore.

PMID- 24909421
TI  - Galvez-Markov network transferability indices: review of classic theory and new
      model for perturbations in metabolic reactions.
AB  - Topological Indices (TIs) are numerical parameters useful to carry out
      Quantitative Structure-Property Relationships (QSPR) analysis and predict the
      effect of perturbations in many types of Complex Networks. This work, focuses on
      a very powerful class of TIs called Galvez charge transfer indices. First, we
      review the classic concept and some applications of these indices. Next, we
      review the Galvez-Markov TIs of order k (GMk), a recent generalization to these
      TIs introduced by us. We also reviewed some previous examples of calculation of
      GMk values for different classes of networks, including metabolic networks. Here,
      we also demonstrated that Galvez- Markov TIs are useful to predict perturbations
      and the transferability of biochemical patterns forms metabolic networks of
      species to others. We report a linear QSPR-Perturbation theory model that
      predicts more than 300,000 perturbations in metabolic networks with 85 - 99% of
      good classification in training and validation series.

PMID- 24909422
TI  - The prediction of human intestinal absorption based on the molecular structure.
AB  - Human Intestinal Absorption (HIA) has been modeled many times by using
      classification models. However, regression models are scarce. Here, Artificial
      Neural Networks (ANNs) are implemented for this purpose. A dataset of
      structurally diverse chemicals with their respective experimental HIA were used
      to design robust, true predictive and widespread applicable ANN models. An input
      variables pool was made up of structural invariants calculated by using either
      Dragon or our software Desmol 1. The selection of best variables was performed
      following three steps using the entire dataset of molecules. Firstly, variables
      poorly correlated with the experimental data were eliminated. Secondly, input
      variable selection was performed by stepwise multilinear regression. Thirdly,
      correlation matrix in the set of selected variables was then obtained to
      eliminate those variables strongly intercorrelated. Backpropagation ANNs were
      trained for these variables finally selected as inputs, and HIA as output. The
      training and selection procedure to find robust models consisted of randomly
      partitioning the dataset into three sets: training set, with 50% of the
      population, test set with 25%, and validation set with the other 25%. With each
      partitioning, diverse numbers of hidden nodes were assayed to optimize the
      performance in the prediction for the three sets. Models with r(2) greater than
      0.6 for the three sets were considered as robust. A randomization test following
      all these steps was performed, and the poor results obtained confirm the validity
      of the method presented in this paper to predict HIA for datasets of structurally
      diverse organic compounds. 

PMID- 24909423
TI  - N-linear algebraic maps for chemical structure codification: a suitable
      generalization for atom-pair approaches?
AB  - The present manuscript introduces, for the first time, a novel 3D-QSAR alignment
      free method (QuBiLS-MIDAS) based on tensor concepts through the use of the three
      linear and four-linear algebraic forms as specific cases of n-linear maps. To
      this end, the k(th) three-tuple and four-tuple spatial-(dis)similarity matrices
      are defined, as tensors of order 3 and 4, respectively, to represent
      3Dinformation among "three and four" atoms of the molecular structures. Several
      measures (multi-metrics) to establish (dis)-similarity relations among "three and
      four" atoms are discussed, as well as, normalization schemes proposed for the n
      tuple spatial-(dis)similarity matrices based on the simple-stochastic and mutual
      probability algebraic transformations. To consider specific interactions among
      atoms, both for the global and local indices, n-tuple path and length cut-off
      constraints are introduced. This algebraic scaffold can also be seen as a
      generalization of the vector-matrix-vector multiplication procedure (which is a
      matrix representation of the traditional linear, quadratic and bilinear forms)
      for the calculation of molecular descriptors and is thus a new theoretical
      approach with a methodological contribution. A variability analysis based on
      Shannon's entropy reveals that the best distributions are achieved with the
      ternary and quaternary measures corresponding to the bond and dihedral angles. In
      addition, the proposed indices have superior entropy behavior than the
      descriptors calculated by other programs used in chemo-informatics studies, such
      as, DRAGON, PADEL, Mold2, and so on. A principal component analysis shows that
      the novel 3D n-tuple indices codify the same information captured by the DRAGON
      3D-indices, as well as, information not codified by the latter. A QSAR study to
      obtain deeper criteria on the contribution of the novel molecular parameters was
      performed for the binding affinity to the corticosteroid-binding globulin, using
      Cramer's steroid database. The achieved results reveal superior statistical
      parameters for the Bond Angle and Dihedral Angle approaches, consistent with the
      results obtained in variability analysis. Finally, the obtained QuBiLS-MIDAS
      models yield superior performances than all 3D-QSAR methods reported in the
      literature using the 31 steroids as training set, and for the popular division of
      Cramer's database in training (1-21) and test (22-31) sets, comparable to
      superior results in the prediction of the activity of the steroids are obtained.
      From the results achieved, it can be suggested that the proposed QuBiLS-MIDAS N
      tuples indices are a useful tool to be considered in chemo-informatics studies. 

PMID- 24909419
TI  - A 30-years review on pharmacokinetics of antibiotics: is the right time for
      pharmacogenetics?
AB  - Drug bioavailability may vary greatly amongst individuals, affecting both
      efficacy and toxicity: in humans, genetic variations account for a relevant
      proportion of such variability. In the last decade the use of pharmacogenetics in
      clinical practice, as a tool to individualize treatment, has shown a different
      degree of diffusion in various clinical fields. In the field of infectious
      diseases, several studies identified a great number of associations between host
      genetic polymorphisms and responses to antiretroviral therapy. For example, in
      patients treated with abacavir the screening for HLA-B*5701 before starting
      treatment is routine clinical practice and standard of care for all patients;
      efavirenz plasma levels are influenced by single nucleotide polymorphism (SNP)
      CYP2B6-516G>T (rs3745274). Regarding antibiotics, many studies investigated drug
      transporters involved in antibiotic bioavailability, especially for
      fluoroquinolones, cephalosporins, and antituberculars. To date, few data are
      available about pharmacogenetics of recently developed antibiotics such as
      tigecycline, daptomycin or linezolid. Considering the effect of SNPs in gene
      coding for proteins involved in antibiotics bioavailability, few data have been
      published. Increasing knowledge in the field of antibiotic pharmacogenetics could
      be useful to explain the high drug inter-patients variability and to
      individualize therapy. In this paper we reported an overview of pharmacokinetics,
      pharmacodynamics, and pharmacogenetics of antibiotics to underline the importance
      of an integrated approach in choosing the right dosage in clinical practice. 

PMID- 24909424
TI  - Review of current chemoinformatic tools for modeling important aspects of CYPs
      mediated drug metabolism. Integrating metabolism data with other biological
      profiles to enhance drug discovery.
AB  - The study of the metabolism of xenobiotics by the human body is an essential
      stage in the complex and expensive process of drug discovery, being one of the
      main causes of disapproval and/or withdrawal of drugs. Regarding this, enzymes
      known as cytochromes P450 (CYPs) play a very decisive role in the
      biotransformation of many chemicals. For this reason, the use of chemoinformatics
      to predict and /or analyze from different points of view CYPs-mediated drug
      metabolism, can help to reduce time and financial resources. This work is focused
      on the most remarkable advances in the last 5 years of the chemoinformatics tools
      towards the virtual analysis of CYPsmediated drug metabolism. First, a brief
      section is dedicated to the applicability of chemoinformatics in different areas
      associated with drug metabolism. Then, both the models for prediction of CYPs
      substrates and those allowing the assessment of sites of metabolism (SOM) are
      discussed. At the same time, the principal limitations of the current
      chemoinformatic tools are pointed out. Finally, and taking into account that
      metabolism is an essential step in the whole process of designing any drug, we
      introduce here as a case of study, the first multitasking model for quantitative
      structure biological effect relationships (mtk-QSBER). The purpose of this model
      is to integrate different types of biological profiles such as ADMET (absorption,
      distribution, metabolism, excretion, toxicity) profiles and antistaphylococci
      activities. The mtk-QSBER model was created by employing a heterogeneous dataset
      of more than 66000 cases tested in 6510 different experimental conditions. The
      model displayed a total accuracy higher than 94%. To the best of our knowledge,
      this is the first attempt to complement metabolism assays with other relevant
      biological data in order to speed up the discovery of efficacious
      antistaphylococci agents. 

PMID- 24909425
TI  - Development of crayfish bio-based plastic materials processed by small-scale
      injection moulding.
AB  - BACKGROUND: Protein has been investigated as a source for biodegradable polymeric
      materials. This work evaluates the development of plastic materials based on
      crayfish and glycerol blends, processed by injection moulding, as a fully
      biodegradable alternative to conventional polymer-based plastics. The effect of
      different additives, namely sodium sulfite or bisulfite as reducing agents, urea
      as denaturing agent and L-cysteine as cross-linking agent, is also analysed.
      RESULTS: The incorporation of any additive always yields an increase in energy
      efficiency at the mixing stage, but its effect on the mechanical properties of
      the bioplastics is not so clear, and even dampened. The additive developing a
      greater effect is L-cysteine, showing higher Young's modulus values and
      exhibiting a remnant thermosetting potential. Thus, processing at higher
      temperature yields a remarkable increase in extensibility. CONCLUSION: This work
      illustrates the feasibility of crayfish-based green biodegradable plastics,
      thereby contributing to the search for potential value-added applications for
      this by-product.

PMID- 24909426
TI  - EGF regulates claudin-2 and -4 expression through Src and STAT3 in MDCK cells.
AB  - Epidermal Growth Factor (EGF) is a key regulator of epithelial paracellular
      permeability, a property that depends on tight junctions (TJ) and can be
      evaluated through the measurement of the transepithelial electrical resistance
      (TER). EGF increases the TER of MDCK monolayers by inducing ERK1/2-dependent
      downregulation of claudin-2 (CLDN-2) and upregulation of claudin-4 (CLDN-4).
      Because either increments or decrements in TER often involve Src activation and
      epithelial cell differentiation occasionally depends on STAT3, here we
      investigated whether EGF might control CLDN-2 downregulation and CLDN-4
      upregulation through those proteins. We found that EGF induces Src activation
      necessary for the reduction of CLDN-2 at the TJ, the degradation of this CLDN,
      the reduction of the cellular levels of its mRNA and the resulting increase of
      TER. EGF-induced changes on CLDN-2 protein and mRNA also depend on STAT3
      activity. This growth factor increases the levels of STAT3 phosphorylated at Y705
      in the nucleus, a process that depends on Src activation. Interestingly, Src and
      STAT3 activation do not exclusively mediate the EGF-induced downregulation of
      CLDN-2, but they are also implicated in the EGF-induced CLDN-4 transcription,
      translation, and exocytic fusion into TJ. Our results indicate that EGF controls
      the levels of CLDN-2 and -4 proteins and mRNAs through Src and STAT3 activity.

PMID- 24909427
TI  - A novel pH-responsive interpolyelectrolyte hydrogel complex for the oral delivery
      of levodopa. Part I. IPEC modeling and synthesis.
AB  - This study was undertaken to synthesize an interpolyelectrolyte complex (IPEC) of
      polymethacrylate (E100) and sodium carboxymethylcellulose (NaCMC) to form a
      polymeric hydrogel material for application in specialized oral drug delivery of
      sensitive levodopa. Computational modeling was employed to proffer insight into
      the interactions between the polymers. In addition, the reactional profile of
      NaCMC and polymethacrylate was elucidated using molecular mechanics energy
      relationships (MMER) and molecular dynamics simulations (MDS) by exploring the
      spatial disposition of NaCMC and E100 with respect to each other. Computational
      modeling revealed that the formation of the IPEC was due to strong ionic
      associations, hydrogen bonding, and hydrophilic interactions. The computational
      results corroborated well with the experimental and the analytical data.

PMID- 24909428
TI  - Incidence of nonconfounded post-computed tomography acute kidney injury in
      hospitalized patients with stable renal function receiving intravenous iodinated
      contrast material.
AB  - OBJECTIVE: The purpose of our investigation was to determine the frequency of
      proximate acute and chronic confounding risk factors for acute kidney injury
      (AKI) in a cohort of adult hospitalized patients with stable renal function who
      developed AKI following an intravenous (IV) contrast-enhanced computed tomography
      (CT) examination. MATERIALS AND METHODS: Institutional review board approval was
      obtained for this retrospective, Health Insurance Portability and Accountability
      Act-compliant investigation. Overall, 100 adult inpatients (50 males [mean age =
      61 years, range: 24-94 years] and 50 females [mean age = 60 years, range: 20-95
      years]) with stable pre-CT renal function who developed post-CT AKI using the
      Acute Kidney Injury Network (AKIN) laboratory criteria following an IV contrast
      enhanced CT examination comprised the study population. Electronic International
      Classification of Disease-9 analysis followed by a comprehensive manual
      electronic medical record review was systematically performed by 5 radiologists
      to identify known acute (n = 24, within 5 days before or 3 days after CT) and
      chronic (n = 21) risk factors for AKI other than contrast material administration
      that might confound a diagnosis of contrast-induced nephrotoxicity. Descriptive
      statistics were performed. RESULTS: Of 100 inpatients with post-CT AKI, 99 (99%)
      had 1 or more acute risk factor(s) for AKI other than contrast material
      administration (median = 3 risk factors, range: 0-8) and 86 (86%) had one or more
      chronic risk factor(s) for AKI (median = 2 risk factors, range: 0-7). The median
      number of risk factors (acute or chronic) per patient was 5 (range: 1-13). Only 1
      inpatient (1%) developed post-CT AKI without a confounding acute risk factor
      (estimated glomerular filtration rate = 62-71 mL/min/1.73 m(2), 4 chronic risk
      factors, and CT 7 days after pancreaticoduodenectomy). The most common acute risk
      factors were nephrotoxic medications (83%) and parenteral blood product
      administration (30%). The most common chronic risk factors were hypertension
      (59%) and chronic kidney disease (56%). CONCLUSION: Nonconfounded post-CT AKI is
      rare in hospitalized adults with stable renal function who have been exposed to
      IV low- or iso-osmolality iodinated contrast material.

PMID- 24909429
TI  - Thymus cDNA library survey uncovers novel features of immune molecules in Chinese
      giant salamander Andrias davidianus.
AB  - A ranavirus-induced thymus cDNA library was constructed from Chinese giant
      salamander, the largest extant amphibian species. Among the 137 putative immune
      related genes derived from this library, these molecules received particular
      focus: immunoglobulin heavy chains (IgM, IgD, and IgY), IFN-inducible protein 6
      (IFI6), and T cell receptor beta chain (TCRbeta). Several unusual features were
      uncovered: IgD displays a structure pattern distinct from those described for
      other amphibians by having only four constant domains plus a hinge region. A
      unique IgY form (IgY(DeltaFc)), previously undescribed in amphibians, is present
      in serum. Alternative splicing is observed to generate IgH diversification. IFI6
      is newly-identified in amphibians, which occurs in two forms divergent in
      subcelluar distribution and antiviral activity. TCRbeta immunoscope profile
      follows the typical vertebrate pattern, implying a polyclonal T cell repertoire.
      Collectively, the pioneering survey of ranavirus-induced thymus cDNA library from
      Chinese giant salamander reveals immune components and characteristics in this
      primitive amphibian. 

PMID- 24909432
TI  - Ultrafast charge separation and nongeminate electron-hole recombination in
      organic photovoltaics.
AB  - The mechanism of electron-hole separation in organic solar cells is currently
      hotly debated. Recent experimental work suggests that these charges can separate
      on extremely short timescales (<100 fs). This can be understood in terms of
      delocalised transport within fullerene aggregates, which is thought to emerge on
      short timescales before vibronic relaxation induces polaron formation. However,
      in the optimal heterojunction morphology, electrons and holes will often re
      encounter each other before reaching the electrodes. If such charges trap and
      cannot separate, then device efficiency will suffer. Here we extend the theory of
      ultrafast charge separation to incorporate polaron formation, and find that the
      same delocalised transport used to explain ultrafast charge separation can
      account for the suppression of nongeminate recombination in the best devices. 

PMID- 24909430
TI  - Interleukin-21 promotes germinal center reaction by skewing the follicular
      regulatory T cell to follicular helper T cell balance in autoimmune BXD2 mice.
AB  - OBJECTIVE: Follicular regulatory T (Tfr) cells act as the regulatory counterpart
      of follicular helper T (Tfh) cells to suppress germinal center (GC) B cell
      differentiation. We recently showed that interleukin-21 (IL-21) promoted Tfh cell
      differentiation in autoimmune BXD2 mice that develop spontaneous GCs. This study
      was undertaken to determine the modulatory effects of IL-21 on Tfr cells and the
      Tfr cell to Tfh cell balance in BXD2 mice. METHODS: The percentage and phenotype
      of Tfr cells were determined in BXD2 and BXD2-IL21(-/-) mice. The effects of IL
      21 on Tfr cells and the Tfr cell:Tfh cell ratio were evaluated. Sorted Tfr cells
      from BXD2-IL21(-/-) mice were cocultured with Tfh cells and B cells, or
      transferred into BXD2 mice to determine their function. RESULTS: The percentages
      and numbers of GC B cells and Tfh cells were significantly reduced, but the
      percentage of Tfr cells was 2-fold higher in BXD2-IL21(-/-) mice than in wild
      type BXD2 mice. Administration of AdIL-21 to BXD2-IL21(-/-) mice decreased the
      percentages and numbers of Tfr cells and the Tfr cell:Tfh cell ratio but
      increased the number of GC B cells in the spleen. Recombinant murine IL-21
      suppressed FoxP3 and significantly reduced Tgfb1, Il2, and Gitr but enhanced
      Il21, Il6, Pd1, Cxcr5, and Icos expression in Tfr cells. IL-21 also counteracted
      Tfr cell-mediated inhibition of antibody secretion in the Tfh cell-B cell
      coculture system. Transfer of Tfr cells into young BXD2 mice reduced GC size and
      decreased the numbers of autoantibody-producing B cells. CONCLUSION: Our findings
      indicate that high levels of IL-21 selectively enhance Tfh cell differentiation
      but inhibit Tfr cell commitment and the suppressive function of Tfr cells on Tfh
      cells and B cells, suggesting that IL-21 skews the balance from Tfr cells to Tfh
      cells to promote autoreactive GC reactions in BXD2 mice.

PMID- 24909431
TI  - Multifidus muscle size and percentage thickness changes among patients with
      unilateral chronic low back pain (CLBP) and healthy controls in prone and
      standing.
AB  - The aim of this study was to determine if differences exist in lumbar multifidus
      (LM) thickness at rest and during activation, between individuals with chronic
      low back pain (CLBP) and controls. Lumbar multifidus thickness was assessed via
      rehabilitative ultrasound imaging (RUSI), and was performed in prone and standing
      both at rest and during muscle activation i.e. with a contralateral arm lift
      (CAL). Twenty participants were assessed; ten CLBP participants and ten controls.
      Rehabilitative ultrasound imaging was used to measure LM thickness and percentage
      thickness change at L4/L5 and L5/S1 in four positions; prone at rest, prone
      during activation with a CAL, standing at rest, and standing during activation
      with a CAL. Independent and paired t-tests were used to calculate differences in
      LM thickness and percentage thickness change between groups, and also between
      sides in the CLBP group. There was a significant difference in LM percentage
      thickness change in standing during activation with a CAL; the CLBP demonstrated
      a greater percentage thickness increase at L5/S1 compared to the controls, (p =
      0.05). There were no differences between groups at the L4/L5 level for this
      position. There were no differences between the groups for LM thickness or
      percentage thickness change in prone or standing at rest, or during activation
      with a CAL in prone. Within the CLBP group, no significant between side
      differences were found. These results give preliminary insight into possible
      differences in LM contractile behaviour during functional movements in CLBP,
      however, larger scale research is warranted. 

PMID- 24909433
TI  - Acid-free regioselective aminocarbonylation of alkenes.
AB  - An efficient method for the synthesis of N-aryl monosubstituted carboxamides via
      the Pd-catalyzed carbonylation of alkenes with CO and amines is described.
      Mechanistic insights for this highly selective reaction are provided. 

PMID- 24909434
TI  - Development and validation of the ACE tool: assessing medical trainees'
      competency in evidence based medicine.
AB  - BACKGROUND: While a variety of instruments have been developed to assess
      knowledge and skills in evidence based medicine (EBM), few assess all aspects of
      EBM - including knowledge, skills attitudes and behaviour - or have been
      psychometrically evaluated. The aim of this study was to develop and validate an
      instrument that evaluates medical trainees' competency in EBM across knowledge,
      skills and attitude. METHODS: The 'Assessing Competency in EBM' (ACE) tool was
      developed by the authors, with content and face validity assessed by expert
      opinion. A cross-sectional sample of 342 medical trainees representing 'novice',
      'intermediate' and 'advanced' EBM trainees were recruited to complete the ACE
      tool. Construct validity, item difficulty, internal reliability and item
      discrimination were analysed. RESULTS: We recruited 98 EBM-novice, 108 EBM
      intermediate and 136 EBM-advanced participants. A statistically significant
      difference in the total ACE score was observed and corresponded to the level of
      training: on a 0-15-point test, the mean ACE scores were 8.6 for EBM-novice; 9.5
      for EBM-intermediate; and 10.4 for EBM-advanced (p < 0.0001). Individual item
      discrimination was excellent (Item Discrimination Index ranging from 0.37 to
      0.84), with internal reliability consistent across all but three items (Item
      Total Correlations were all positive ranging from 0.14 to 0.20). CONCLUSION: The
      15-item ACE tool is a reliable and valid instrument to assess medical trainees'
      competency in EBM. The ACE tool provides a novel assessment that measures user
      performance across the four main steps of EBM. To provide a complete suite of
      instruments to assess EBM competency across various patient scenarios, future
      refinement of the ACE instrument should include further scenarios across harm,
      diagnosis and prognosis.

PMID- 24909435
TI  - Changes in motor cortical excitability in patients with Sydenham's chorea.
AB  - BACKGROUND AND PURPOSE: The neurophysiological characteristics of motor cortex
      have been well characterized in patients with Huntington's disease. We present
      the first data on cortical excitability in patients with Sydenham's chorea.
      METHODS: Motor cortex excitability was examined using transcranial magnetic
      stimulation in 16 patients in the early clinical stages of Sydenham's chorea and
      in 17 age- and sex-matched control subjects. Investigations included resting and
      active motor threshold, motor evoked potential, input-output curves,
      contralateral silent period, and transcallosal inhibition. RESULTS: Resting and
      active motor threshold were significantly higher and motor evoked potentials were
      significantly smaller in patients in comparison with controls. The input-output
      curves were shallower in both hemispheres of patients with chorea compared with
      controls. No significant differences were seen in silent period or transcallosal
      inhibition duration. CONCLUSION: Sydenham's chorea is characterized by reduced
      excitability of corticospinal output similar to that observed in Huntington's
      disease.

PMID- 24909436
TI  - Comparison of backbone modification in protein beta-sheets by alpha->gamma
      residue replacement and alpha-residue methylation.
AB  - The mimicry of protein tertiary structure by oligomers with unnatural backbones
      is a significant contemporary research challenge. Among common elements of
      secondary structure found in natural proteins, sheets have proven the most
      difficult to address. Here, we report the systematic comparison of different
      strategies for peptide backbone modification in beta-sheets with the goal of
      identifying the best method for replacing a multi-stranded sheet in a protein
      tertiary fold. The most effective sheet modifications examined led to native-like
      tertiary folding behavior with a thermodynamic folded stability comparable to the
      prototype protein on which the modified backbones are based. 

PMID- 24909437
TI  - A facile approach for the polymer grafting of silica based on tandem reversible
      addition fragmentation chain transfer/click chemistry and its application in high
      performance liquid chromatography.
AB  - In this work, a tandem reversible addition fragmentation chain transfer
      (RAFT)/click chemistry method was developed to prepare amide-polystyrene-silica
      (NHCO-Psty-silica) stationary phase. Styrene was immobilized on amino-silica
      surface via an azide functionalized RAFT agent in a one-pot procedure. The
      resultant NHCO-Psty-silica column demonstrates better performance for shielding
      of residue silanols than traditional ODS column, which was ascertained by
      Engelhardt test (E test), Tanaka test (T test), Galushko test (G test), and
      Walters test (W test). Our results showed lower values of silanol activity
      calculated according to the formula in these standard tests for NHCO-Psty-silica
      column compared to the ODS column we tested. As a result, the NHCO-Psty-silica is
      suitable for the separation of basic compounds. The hydrophobic, anion exchanging
      and pi-pi interaction of the column toward analytes were also evaluated.
      Moreover, the NHCO-Psty-silica column also showed excellent stability with pure
      water as mobile phase. 

PMID- 24909438
TI  - Analysis of endocrine disrupters and related compounds in sediments and sewage
      sludge using on-line turbulent flow chromatography-liquid chromatography-tandem
      mass spectrometry.
AB  - A novel fully automated method based on dual column switching using turbulent
      flow chromatography followed by liquid chromatography coupled to tandem mass
      spectrometry (TFC-LC-MS/MS) was applied for the determination of endocrine
      disruptors (EDCs) and related compounds in sediment and sewage sludge samples.
      This method allows the unequivocal identification and quantification of the most
      relevant environmental EDCs such as natural and synthetic estrogens and their
      conjugates, antimicrobials, parabens, bisphenol A (BPA), alkylphenolic compounds,
      benzotriazoles, and organophosphorus flame retardants, minimizing time of
      analysis and alleviating matrix effects. Applying this technique, after the
      extraction of the target compounds by pressurized liquid extraction (PLE),
      sediment and sewage sludge extracts were directly injected to the chromatographic
      system and the analytes were concentrated into the clean-up loading column. Using
      six-port switching system, the analytes were transferred to the analytical column
      for subsequent detection by MS-MS (QqQ). In order to optimize this multiplexing
      system, a comparative study employing six types of TurboFlowTM columns, with
      different chemical modifications, was performed to achieve the maximum retention
      of analytes and best elimination of matrix components. Using the optimized
      protocol low limits of quantification (LOQs) were obtained ranging from 0.0083 to
      1.6 ng/g for sediment samples and from 0.10 to 125 ng/g for sewage sludge samples
      (except for alkylphenol monoethoxylate). The method was used to evaluate the
      presence and fate of target EDCs in the Ebro River which is the most important
      river in Spain with intensive agricultural and industrial activities in the basin
      that contribute to deteriorating soil and water quality.

PMID- 24909439
TI  - Experimental and numerical validation of the effective medium theory for the B
      term band broadening in 1st and 2nd generation monolithic silica columns.
AB  - Effective medium theory (EMT) expressions for the B-term band broadening in
      monolithic silica columns are presented at the whole-column as well as at the
      mesoporous skeleton level. Given the bi-continuous nature of the monolithic
      medium, regular as well as inverse formulations of the EMT-expressions have been
      established. The established expressions were validated by applying them to a set
      of experimental effective diffusion (Deff)-data obtained via peak parking on a
      number of 1st and 2nd generation monolithic silica columns, as well as to a set
      of numerical diffusion simulations in a simplified monolithic column
      representation (tetrahedral skeleton model) with different external porosities
      and internal diffusion coefficients. The numerically simulated diffusion data can
      be very closely represented over a very broad range of zone retention factors (up
      to k"=80) using the established EMT-expressions, especially when using the
      inverse variant. The expressions also allow representing the experimentally
      measured effective diffusion data very closely. The measured Deff/Dmol-values
      were found to decrease significantly with increasing retention factor, in general
      going from about Deff/Dmol=0.55 to 0.65 at low k" (k"?1.5-3.8) to Deff/Dmol=0.25
      at very high k" (k"?40-80). These values are significantly larger than observed
      in fully-porous and core-shell particles. The intra-skeleton diffusion
      coefficient (Dpz) was typically found to be of the order of Dpz/Dmol=0.4,
      compared to Dpz/Dmol=0.2-0.35 observed in most particle-based columns. These
      higher Dpz/Dmol values are the cause of the higher Deff/Dmol values observed. In
      addition, it also appears that the higher internal diffusion is linked to the
      higher porosity of the mesoporous skeleton that has a relatively open structure
      with relatively wide pores. The observed (weak) relation between Dpz/Dmol and the
      zone retention factor appears to be in good agreement with that predicted when
      applying the regular variant of the EMT-expression directly to the mesoporous
      skeleton level. 

PMID- 24909440
TI  - [Resistance to fluoroquinolones in 2013: what are the consequences in internal
      medicine?].
AB  - Because of their important qualities, fluoroquinolones are amongst the most
      prescribed antibiotics in the world. The corollary of this success is the rapid
      increase in resistance to fluoroquinolones, responsible for treatment failures.
      Moreover, fluoroquinolone-resistance is often accompanied by resistance to other
      classes of antibiotics. Currently, significant levels of resistance are found
      both in hospitals and in community settings, severely limiting possibilities for
      empirical use of fluoroquinolones. A major mechanism explaining the rapid
      emergence of resistance to fluoroquinolones is their specific impact on human
      microbiota and the selection of resistant strains in the microbiota, which seems
      to be an unavoidable ecological side effect. In order to preserve the efficiency
      of this important class of antibiotics, limiting their use and respecting good
      practice recommendations are essential. 

PMID- 24909441
TI  - [Angioplasty for atherosclerotic renal artery stenosis: the end of the story?].

PMID- 24909442
TI  - [Hemolytic anemia due to naphthalene poisoning].
AB  - INTRODUCTION: Naphthalene ingestion is a rare cause of hemolysis. CASE REPORT: We
      report a 33-year-old woman, originating from the Comoros, hospitalized for
      intense fatigue associated with delirium, fever and jaundice, three days after
      ritual ingestion of naphthalene. Biochemical parameters showed marked hemolysis.
      Outcome was favorable after red cells transfusion and hydratation with
      intravenous fluids. CONCLUSION: Diagnostic work-up of unexplained hemolysis
      should include the search for toxic exposition. Naphthalene poisoning can present
      with diagnostic challenge for physicians.

PMID- 24909443
TI  - Phenotypic expression in hypertrophic cardiomyopathy and late gadolinium
      enhancement on cardiac magnetic resonance.
AB  - INTRODUCTION AND AIM: The prognostic value of late gadolinium enhancement (LGE)
      for risk stratification of hypertrophic cardiomyopathy (HCM) patients is the
      subject of disagreement. We set out to examine the association between clinical
      and morphological variables, risk factors for sudden cardiac death and LGE in HCM
      patients. METHODS: From a population of 78 patients with HCM, we studied 53 who
      underwent cardiac magnetic resonance. They were divided into two groups according
      to the presence or absence of LGE. Ventricular arrhythmias and morbidity and
      mortality during follow-up were analyzed. RESULTS: Patients with LGE were younger
      at the time of diagnosis (p=0.046) and more often had a family history of sudden
      death (p=0.008) and known coronary artery disease (p=0.086). On echocardiography
      they had greater maximum wall thickness (p=0.007) and left atrial area (p=0.037)
      and volume (p=0.035), and more often presented a restrictive pattern of diastolic
      dysfunction (p=0.011) with a higher E/E ratio (p=0.003) and left ventricular
      systolic dysfunction (p=0.038). Cardiac magnetic resonance supported the
      association between LGE and previous echocardiographic findings: greater left
      atrial area (p=0.029) and maximum wall thickness (p<0.001) and lower left
      ventricular ejection fraction (p=0.056). Patients with LGE more often had an
      implantable cardioverter-defibrillator (ICD) (p=0.015). At follow-up, no
      differences were found in the frequency of ventricular arrhythmias, appropriate
      ICD therapies or mortality. CONCLUSIONS: The presence of LGE emerges as a risk
      marker, associated with the classical predictors of sudden cardiac death in this
      population. However, larger studies are required to confirm its independent
      association with clinical events.

PMID- 24909444
TI  - Diagnostic questions in hypertrophic cardiomyopathy: what is the significance of
      late enhancement on cardiac magnetic resonance?

PMID- 24909445
TI  - Detailed method description for noninvasive monitoring of differentiation status
      of human embryonic stem cells.
AB  - The (non)differentiation status of human embryonic stem cells (hESCs) is usually
      analyzed by determination of key pluripotency defining markers (e.g., OCT4,
      Nanog, SOX2) by means of reverse transcription quantitative polymerase chain
      reaction (RT-qPCR), flow cytometry (FC), and immunostaining. Despite proven
      usefulness of these techniques, their destructive nature makes it impossible to
      follow up on the same hESC colonies for several days, leading to a loss of
      information. In 2003, an OCT4-eGFP knock-in hESC line to monitor OCT4 expression
      was developed and commercialized. However, to the best of our knowledge, the use
      of fluorescence microscopy (FM) for monitoring the OCT4-eGFP expression of these
      cells without sacrificing them has not been described to date. Here, we describe
      such a method in detail, emphasizing both its resolving power and its
      complementary nature to FC as well as the potential pitfalls in standardizing the
      output of the FM measurements. The potential of the method is demonstrated by
      comparison of hESCs cultured in several conditions, both feeder free
      (vitronectin, VN) and grown on feeder cells (mouse embryonic fibroblasts, MEFs). 

PMID- 24909446
TI  - Heparin stability by determining unsubstituted amino groups using hydrophilic
      interaction chromatography mass spectrometry.
AB  - The thermal instability of the anticoagulant heparin is associated, in part, with
      the solvolytic loss of N-sulfo groups. This study describes a new method to
      assess the increased content of unsubstituted amino groups present in thermally
      stressed and autoclave-sterilized heparin formulations. N-Acetylation of heparin
      samples with acetic anhydride-d6 is followed by exhaustive heparinase treatment
      and disaccharide analysis by hydrophilic interaction chromatography mass
      spectrometry (HILIC-MS). The introduction of a stable isotopic label provides a
      sensitive probe for the detection and localization of the lost N-sulfo groups,
      potentially providing valuable insights into the degradation mechanism and the
      reasons for anticoagulant potency loss. 

PMID- 24909447
TI  - Fluorescent peptide sensors for tyrosylprotein sulfotransferase activity.
AB  - Tyrosine sulfurylation is a post-translational modification important for protein
      protein interactions in the extracellular space that are instrumental in cell
      adhesion, cell signaling, immune responses, and pathogen recognition of host
      cells. Tyrosine sulfurylation is catalyzed by the tyrosylprotein
      sulfotransferases (TPSTs), and in humans there are two isoforms: hTPST1 and
      hTPST2. The study of hTPST function and the development of small molecule probes
      to examine the role of hTPSTs in cell biology have been delayed by the absence of
      a continuous direct assay for hTPST activity. We have developed a fluorescent
      peptide-based assay to directly monitor tyrosine sulfurylation in real time. TPST
      mediated tyrosine sulfurylation of the peptides disrupts fluorophore quenching
      and results in increased fluorescence emission. The assay can be used to study
      TPST enzymatic activity, and we show that recombinant hTPSTs are active in the
      absence of divalent metal ions and that optimal activity is at pH 6.0. We further
      show that the assay can also be used to identify inhibitors of tyrosine
      sulfurylation. A clear understanding of hTPST function in normal cell biology and
      in disease states will require the identification of small molecule inhibitors or
      probes to modulate enzymatic activity, and our results will facilitate that
      process. 

PMID- 24909448
TI  - Twelve-Year Retrospective Follow-Up of Machined Implants in the Posterior
      Maxilla: Radiographic and Peri-Implant Outcome.
AB  - PURPOSE: To retrospectively evaluate the survival rate of machined implants in
      sinus-lifted posterior maxilla after 12 years, with special reference to
      radiographic outcome and peri-implantitis. MATERIALS AND METHODS: From 37
      possible candidates, 29 patients with 59 implants were evaluated. Implants were
      placed in the posterior maxilla in combination with a sinus elevation procedure
      (27 patients) or 6 months after sinus elevation (2 patients). Marginal bone level
      changes were radiographically evaluated at baseline and 1, 7, and 12 years post
      loading. Probing depth was measured; presence/absence of plaque and bleeding on
      probing were recorded. RESULTS: Four out of 59 implants failed in 4 out of 29
      patients (cumulative survival rate = 93.2%). The mean bone loss was 0.78 mm (+/-
      0.88) after 12 years. Changes in the mean bone level were statistically
      significant between baseline and all the other follow-up intervals (p < .001).
      Statistically significant differences could be demonstrated for the first- to
      12th-year interval (p < .05) and for the seventh- to 12th-year interval (p <
      0.001). No statistically significant differences could be demonstrated at the
      first- to seventh-year interval (p = .32). The mean overall probing depth was 2.9
      +/- 0.66 mm. Probing depth was moderately correlated with the marginal bone
      changes at 7 year and after 12 year follow up (p = .05). No signs of peri
      implantitis were reported during the 12-year follow-up period. CONCLUSIONS: This
      follow-up demonstrates a very good prognosis when implants with machined surfaces
      are used. The frequencies of implant failures were very small. Within the limits
      of the results from this study, the risk of peri-implantitis in the posterior
      maxilla might be considered a minor problem when implants with machined surfaces
      are used.

PMID- 24909449
TI  - Fair innings.
AB  - In many societies, the aging of the population is becoming a major problem. This
      raises difficult issues for ethics and public policy. On what is known as the
      fair innings view, it is not impermissible to give lower priority to policies
      that primarily benefit the elderly. Philosophers have tried to justify this view
      on various grounds. In this article, I look at a consequentialist, a fairness
      based, and a contractarian justification. I argue that all of them have
      implausible implications and fail to correspond to our moral intuitions. I end by
      outlining a different kind of consequentialist justification that avoids those
      implications and corresponds better to our considered moral judgments. 

PMID- 24909450
TI  - Impact of the Scientific Registry of Transplant Recipients' new Bayesian method
      on estimating center effects and flagging of centers as worse than expected.

PMID- 24909451
TI  - Inhalation carcinogenicity of dichloromethane in rats and mice.
AB  - The carcinogenicity of inhaled dichloromethane (DCM) was examined by exposing
      groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of both sexes to 0, 1000,
      2000, or 4000 ppm (w/w) DCM-containing aerosol for 2 years. Inhalation of DCM
      resulted in increased incidences of subcutis fibromas, mammary gland
      fibroadenoma, and peritoneum mesotheliomas in male rats; mammary gland
      fibroadenomas in female rats; and bronchiolar-alveolar adenomas and carcinomas in
      the lung and hepatocellular adenomas and carcinomas in male and female mice.
      These results clearly indicate that inhaled DCM is carcinogenic in F344/DuCrj
      (SPF) rats and Crj: BDF1 (SPF) mice.

PMID- 24909452
TI  - Gold-catalyzed direct hydrogenative coupling of nitroarenes to synthesize
      aromatic azo compounds.
AB  - The azo linkage is a prominent chemical motif which has found numerous
      applications in materials science, pharmaceuticals, and agrochemicals. Described
      herein is a sustainable heterogeneous-gold-catalyzed synthesis of azo arenes.
      Available nitroarenes are deoxygenated and linked selectively by the formation of
      N=N bonds using molecular H2 without any external additives. As a result of a
      unique and remarkable synergy between the metal and support, a facile surface
      mediated condensation of nitroso and hydroxylamine intermediates is enabled, and
      the desired transformation proceeds in a highly selective manner under mild
      reaction conditions. The protocol tolerates a large variety of functional groups
      and offers a general and versatile method for the environmentally friendly
      synthesis of symmetric or asymmetric aromatic azo compounds.

PMID- 24909453
TI  - Evaluating ear cartilage piercing practices in London, UK.
AB  - BACKGROUND: Ear cartilage piercing is increasingly popular and has a significant
      complication rate. Contrary to popular belief, there are no minimum
      qualifications required to practice ear piercing. This study evaluated ear
      cartilage piercing practices in London, UK. METHOD: Practitioners at 25 piercing
      parlours completed a telephone questionnaire assessing piercing practice.
      RESULTS: Ninety-six per cent of practitioners were aware of the risk of infection
      post-piercing. Four per cent, 12 per cent and 0 per cent of practitioners were
      aware of keloid scarring, hypertrophic scarring and cauliflower ear respectively.
      No practitioners were aware of any other complications. Their consent forms did
      not document any ear cartilage complications. Twenty-eight per cent of
      participants advised clients to seek medical attention following a complication.
      Forty per cent did not provide written post-piercing guidance. CONCLUSION:
      Piercing practitioners were insufficiently aware of ear cartilage piercing
      complications. It is unlikely that informed consent was obtained prior to
      piercing. The post-piercing practice of the majority of parlours did not follow
      published national guidance.

PMID- 24909456
TI  - Pancreatic islet transplantation: from dogs to humans and back again.
AB  - Pancreatic islet transplantation is a cell-based therapy that provides a
      potential cure for type 1 diabetes mellitus. After the introduction of an
      automated method for islet isolation and steroid-free immunosuppressive
      protocols, reversal of diabetes by islet transplantation is now performed at
      major human medical centers around the world. Despite extensive use of animal
      models in islet transplantation research, practical concerns have slowed the
      introduction of the technique into clinical veterinary practice and only a small
      number of studies have reported results of transplantation in dogs with
      spontaneously occurring diabetes mellitus; however, recent advances in islet
      isolation and encapsulation may make it possible to perform islet transplantation
      without immunosuppression in companion animals. This review summarizes
      experimental and clinical studies of pancreatic islet transplantation in dogs,
      including future directions for cell therapy in animals with naturally occurring
      disease. 

PMID- 24909454
TI  - Management of patients with overt or resolved hepatitis B virus infection
      undergoing rituximab therapy.
AB  - INTRODUCTION: Rituximab (RTX), a chimeric mouse anti-human CD20 monoclonal
      antibody, is indicated for the treatment of patients with non-Hodgkin's lymphoma,
      chronic lymphocytic leukemia, granulomatosis with polyangiitis and microscopic
      polyangiitis, and rheumatoid arthritis, but nowadays it is increasingly used for
      the treatment of many other immune-mediated disorders. Hepatitis B virus (HBV)
      reactivation in RTX-treated patients, eventually leading to fatal liver failure,
      has been reported more often among hepatitis B surface antigen (HBsAg)-positive
      patients (overt infection) than in HBsAg-negative, antibody to hepatitis B core
      antigen (anti-HBc) seropositive patients (resolved infection). AREAS COVERED:
      This paper reviews the safety of RTX in patients with overt or resolved HBV
      infection, providing recommendations for its safe use in such patients. EXPERT
      OPINION: Prior to starting RTX treatment, all patients should be screened for HBV
      infection. While HBsAg-positive active carriers should receive long-term
      antiviral treatment with entecavir (ETV) or tenofovir, inactive carriers are
      candidates for universal prophylaxis with lamivudine, or ETV or tenofovir in
      selected cases, to prevent hepatitis reactivation. Conversely, for HBsAg-negative
      anti-HBc positive carriers, that is, those with resolved HBV infection, universal
      prophylaxis with lamivudine is recommended for those with onco-hematological
      diseases, whereas watchful monitoring of HBsAg/HBV DNA levels is advisable for
      all the other indications.

PMID- 24909457
TI  - Why people seek advice from community pharmacies about skin problems.
AB  - OBJECTIVES: The objective of this study was to explore the reasons why patients
      with undiagnosed skin problems seek advice at pharmacies. METHODS: Semi
      structured telephone interviews were conducted with patients presenting at
      pharmacies requesting advice for their own (or their child's) undiagnosed skin
      problem. KEY FINDINGS: Twenty-five patients were interviewed. Key themes around
      choice of pharmacy were convenience of professional advice, triage to general
      practitioner (GP) care if warranted, inaccessibility of GP care and perceived non
      serious nature of the condition. Interviewees also described high levels of trust
      in their pharmacists. Few concerns were noted, but those that were centred on
      lack of privacy and the potential for misdiagnosis. Almost all participants felt
      positive about their pharmacy care and would re-visit for future skin problems.
      CONCLUSIONS: Patients with undiagnosed skin problems seek advice from pharmacies
      for reasons of professional advice, accessibility, familiarity and trust and
      because they perceive their conditions as non-serious.

PMID- 24909458
TI  - Protective effect of alpha glucosyl hesperidin (G-hesperidin) on chronic vanadium
      induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley
      rats.
AB  - The study was conducted to evaluate the vanadium-induced testicular toxicity and
      its effect on sperm parameters, sperm nuclear DNA damage and histological
      alterations in Sprague Dawley rats and to assess the protective effect of G
      hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg
      kg bw(-1) for 90 days resulted in significant reduction in serum testosterone
      levels, sperm count and motility. Further, a parallel increase in abnormal sperm
      morphology and adverse histopathological changes in testis was also associated
      with vanadium administration when compared to normal control. Moreover, sperm
      chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA
      fragmentation. A marked increase in testicular malondialdehyde levels and
      decreased activity of antioxidant enzymes such as superoxide dismutase and
      catalase indicates vanadium-induced oxidative stress. Co-administration of G
      hesperidin at a dose of 25 and 50 mg kg bw(-1) significantly attenuated the sperm
      parameters and histological changes by restoring the antioxidant levels in rat
      testis. These results suggested that vanadium exposure caused reduced
      bioavailability of androgens to the tissue and increased free radical formation,
      thereby causing structural and functional changes in spermatozoa. G-hesperidin
      exhibited antioxidant effect by protecting the rat testis against vanadium
      induced oxidative damage, further ensures antioxidant potential of bioflavonoids.

PMID- 24909459
TI  - Trauma death in a resource constrained setting: mechanisms and contributory
      factors, the result of analysing 147 cases.
AB  - AIMS AND OBJECTIVES: The objective of the following study is to analyze the
      trauma type (causes), injury pattern and factors that may have contributed to
      death within 72 h of admission into our emergency department (E.D). MATERIALS AND
      METHODS: An 18 month prospective observational study, done from April 2009 to
      September 2010. All the patients were that admitted for 72 h following a full
      assessment by the attending clinician were enlisted for the study. The
      demographic data of each patient, time of arrival at the E.D, type of injury
      sustained, time of incident, previous care at any peripheral hospital, clinical
      state of the patient, Glasgow coma scale (GCS), Injury severity score (ISS) and
      treatment offered before death were entered into a Proforma. DATA ANALYSIS: This
      was done using EPI-Info statistical programme version 3.4.3 of 2007(by CDC
      Atlanta Georgia , USA). RESULTS: A total of 4011 patients were seen in the E.D
      during the period. 1943 (48.4%), were trauma emergencies, with a (147; 41.4%)
      mortality. Their ages ranged from 4 to 87 years, with an average of 34.5 years.
      The male:female ratio was 7:1. The assessed GCS ranged from 6 to 15, with an
      average of 9.1, the ISS ranged from 9 to 75 with an average of 31.3. Road traffic
      accidents (RTAs) accounted for 118 (80.3%) of the deaths, assaults 14.3%, falls
      from height 4.0% and gunshot injuries 1.4%. The overall mortality was 17.1%.
      CONCLUSION: The major source of trauma death was RTA; The most frequently injured
      part of the body was head, with death resulting clinically hemorrhage. The 17.1%
      mortality is multifactorial: The late presentation (in some cases occasioned by
      interference by persons not knowledgeable in the basics of trauma care) lack of
      trained personnel and the systemic deficiencies.

PMID- 24909460
TI  - Injection safety practices among resident doctors in a tertiary health facility
      in Benin City.
AB  - INTRODUCTION: Unsafe injections are a major source of infection with blood borne
      pathogens including hepatitis B virus, hepatitis C virus and human
      immunodeficiency virus. World Health Organization estimates the burden of disease
      associated with unsafe injection practices to be about 1.3 million early deaths,
      loss of about 26 million years of life and an annual burden of 535 million US
      dollars in direct medical costs. The present study was aimed at determining the
      prevalence of needle stick injury and the level of reporting among resident
      doctors in University of Benin Teaching Hospital, Benin. METHODOLOGY: A
      descriptive cross-sectional study was carried out from September 2009 to March
      2010 among 152 resident doctors in a tertiary health facility in Benin City. The
      study population was stratified based on their specialty of training.
      Proportional allocation was applied to obtain the number of participants to be
      selected from each stratum. Self-administered questionnaire was used to collect
      data and analysis was by Statistical Package for Scientific Solution (SPSS)
      version 16.0. (IBM SPSS solution for Education) RESULT: The prevalence of needle
      stick injury among the respondents was 61.8%. The most frequent reason for non
      reporting was; the injury was due to a clean needle 68.9%. Awareness of reporting
      was 92.1% but the level of reporting was 14.9%. CONCLUSION: The prevalence of
      needle stick injury was high, awareness of reporting was high but the level of
      reporting was low. Behavior change communication models are required to bring
      about a positive change in the practice of reporting.

PMID- 24909461
TI  - Effect of dentin desensitizing procedures on methyl methacrylate diffusion
      through dentin.
AB  - BACKGROUND: Acrylic and bisacryl resins are widely used both during the
      temporization phase as well as for provisional restorations and the effect of
      external agents on dentin sensitivity can be reduced by the obliteration of the
      tubules. OBJECTIVE: The purpose of this study was to evaluate diffusion of methyl
      methacrylate monomer through dentin by high performance liquid chromatography
      (HPLC) after three different desensitizing procedures during the fabrication of
      two different provisional crown materials. MATERIALS AND METHODS: Forty extracted
      restoration and caries free human premolar teeth were used in this study.
      Thermoplastic vacuum formed material was used as a matrix to fabricate
      provisional restorations for each tooth before crown preparation. Teeth were
      prepared for a metal supported ceramic crown with 1 mm shoulder margins and then
      crown parts were separated from cementoenamel junction with a carborundum disk
      perpendicular to the long axis of the teeth. To the cementoenamel junction of
      each tooth a polypropylene chamber was attached that contains 1.5 cm 3 of
      deionized distilled water. Prepared teeth were divided into four groups ( n = 10)
      including control, desensitizing agent (DA) application, neodymium-doped yttrium
      aluminum garnet (Nd: YAG) laser irradiation (LI), and LI after DA application
      groups. After application of DA (except control) each group were divided into two
      subgroups for fabrication of provisional restorations ( n = 5). Two
      autopolymerizing provisional materials (Imident (Imicryl) and Systemp C and B
      (Ivoclar, vivadent)) were used to fabricate provisional restorations using the
      strips. Water elutes were analyzed by HPLC at 10 min and 24 h. RESULTS: The
      monomer diffusion values varied statistically according to desensitizing
      procedures, provisional resin systems, and the time periods. Monomer diffusion
      through dentin surfaces desensitized with Nd: YAG LI after DA application was the
      lowest. CONCLUSIONS: Nd: YAG LI in association with DA application is an
      effective combination to eliminate monomer diffusion through dentin to pulpal
      chamber.

PMID- 24909462
TI  - The accuracy rate of Alvarado score, ultrasonography, and computerized tomography
      scan in the diagnosis of acute appendicitis in our center.
AB  - OBJECTIVE: In this study, we aim to compare the relationship between the Alvarado
      score, ultrasonography, and multislice computerized tomography (CT) findings used
      for the diagnosis of the patients who presented to our emergency unit with
      clinical features suggestive of acute appendicitis. MATERIALS AND METHODS:
      Seventy-four patients operated with the diagnosis of acute appendicitis were
      included in the study. The demographic characteristics of the patients, physical
      findings, blood parameters, Alvarado scores, the radiological method used for the
      diagnosis, the surgical methods (open or laparoscopic) and the pathology results
      were recorded on the standard proforma. The collected data were analyzed with
      Statistical Package for Social Sciences (SPSS 15 for Windows, SPSS Inc., Chicago,
      Illinois, USA) computer program. RESULTS: During study period, the sensitivity of
      ultrasonography was found to be as 71.2%, specificity as 46.7%, the positive
      predictive value (PPV) as 82.2%, the negative predictive value (NPV) as 31.8%,
      and the accuracy rate was determined as 65.7%. The sensitivity of tomography was
      determined as 97.2%, the specificity as 62.5%, PPV as 92.1%, and NPV as 83.3%,
      and the accuracy rate was determined as 90%. The sensitivity of the Alvarado
      score was calculated as 54%, the specificity as 73.3%, the PPV as 88.2% and the
      NPV as 29.7%, and the accuracy rate was determined as 57.7%. CONCLUSION: In
      conclusion, computerized tomography (CT) was found to have higher specificity and
      sensitivity than Alvarado score and USG which are not sufficient on their own for
      taking the decision for surgery. We also found that CT scan had lower negative
      laparotomy rate when compared with the other two modalities.

PMID- 24909463
TI  - Current approaches for assessment and treatment of women with early miscarriage
      or ectopic pregnancy in Nigeria: a case for dedicated early pregnancy services.
AB  - CONTEXT: It has been suggested that women with early miscarriage or ectopic
      pregnancy are best cared for in dedicated units which offer rapid and definitive
      ultrasonographic and biochemical assessment at the initial review of the patient.
      AIMS: To describe the current protocols for the assessment and treatment of women
      with early miscarriage or ectopic pregnancy as reported by Nigerian
      Gynecologists, and determine if dedicated early pregnancy services such as Early
      Pregnancy Assessment Units could be introduced to improve care. SETTINGS AND
      DESIGN: A cross-sectional survey of Nigerian Gynecologists attending the 46 th
      Annual Scientific Conference of the Society of Gynaecology and Obstetrics of
      Nigeria. MATERIALS AND METHODS: This was a questionnaire-based study. STATISTICAL
      ANALYSIS: Data analysis was by descriptive statistics using Statistical Package
      for the Social Sciences software, version 17.0 for Windows (IBM Corporation,
      Armonk, NY, USA). RESULTS: A total of 232 gynecologists working in 52 different
      secondary and tertiary health facilities participated in the survey. The mean age
      of the respondents was 42.6 +/- 9.1 years (range 28-70 years). The proportion of
      gynecologists reporting that women with early miscarriage or ectopic pregnancy
      were first managed within the hospital general emergency room was 92%. The mean
      reported interval between arrival in hospital and first ultrasound scan was 4.9
      +/- 1.4 hours (range 1/2-8 hours). Transvaginal scan was stated as the routine
      initial imaging investigation by only 17.2% of respondents. Approximately 94.8%
      of respondents felt that dedicated early pregnancy services were feasible and
      should be introduced to improve the care of women with early miscarriage and
      ectopic pregnancy. CONCLUSIONS: Reported protocols for managing early miscarriage
      or ectopic pregnancy in many health facilities in Nigeria appear to engender
      unnecessary delays and avoidable costs, and dedicated early pregnancy services
      could be both useful and feasible in addressing these shortcomings in the way
      women with such conditions are currently managed.

PMID- 24909464
TI  - Prune belly syndrome: early management outcome of nine consecutive cases.
AB  - BACKGROUND: Prune belly syndrome (PBS) is a rare congenital malformation of
      unclear etiology. The disease progress and outcome in developing countries are
      not clear as most reports are isolated case reports. MATERIALS AND METHODS: A
      review of 9 patients managed for PBS in 5 years. RESULTS: There were 7 males and
      2 females, aged 30 min-11 days (median = 5 days) at the time of presentation (a
      child presented as neonate, defaulted from follow-up and represented at 10 years
      of life). Their weights on admission were 2.5-4.2 kg (median = 3 kg). Maternal
      age range was 26-37 years (median = 32 years), with five mothers being above 30
      years. Seven mothers had febrile illness in the first trimester and took
      antimalarial drugs or antibiotics. Intestinal malrotation was the most common
      associated anomaly. The degree of the anterior abdominal wall and the urinary
      tract morphology varies from patient to patient. Urinary tract anomalies were
      initially managed conservatively. Two infants however later had cutaneous
      ureterostomy due to worsening renal function and recalcitrant urinary tract
      infection (UTI). Four infants had abdominoplasty at the 2 nd week, 6 th week, 3
      rd year and 10 th year of life. Seven orchiopexies were done. Four were done by
      Fowler-Stephen's method while the rest were via the inguinal route. Of the
      former, 3 testicles have normal volume 6 months after, whereas one atrophied.
      Post abdominoplasty, there was a significant reduction in the frequency of
      respiratory tract infection (RTI), UTI and post void urine volume in three
      infants. In addition, there was improved peer interaction and academic
      performance in the 10-year-old child. One infant died of pulmonary hypoplasia and
      two others from worsening urosepsis and progressive renal failure. CONCLUSION:
      PBS presents with a spectrum of features. Initial conservative management of the
      urinary tract was beneficial. Abdominoplasty and orchiopexy have both
      physiological and improved quality of life benefits. Early Parental education
      helped in reducing defaults from follow-up.

PMID- 24909465
TI  - Knowledge and use of emergency contraception by medical doctors on internship in
      a tertiary healthcare facility in Nigeria.
AB  - CONTEXT: Emergency contraception (EC) is widely used to prevent unwanted
      pregnancy and it is largely adopted in many countries as over the counter drug to
      improve access. AIMS: To determine and compare the correct knowledge, attitude
      and current use of EC among newly graduated medical doctors (MDs). SETTINGS AND
      DESIGN: A cross-sectional study conducted among 255 newly graduated MDs at the
      University College Hospital, Ibadan, Nigeria. MATERIALS AND METHODS: A pretested
      self-administered questionnaire was used to obtain data from consenting
      participants. STATISTICAL ANALYSIS USED: Descriptive, bivariate, and
      multivariable analyses were performed, and statistical significance was set at
      0.05. Statistical Package for Social Science version 15.0 (Chicago, IL, USA)
      software was used. RESULTS: The mean age of the respondents was 27.2 years
      (standard deviation = 2.1). The commonest indication for emergency contraceptive
      use mentioned was rape-96.5%. About 70% support EC in Nigeria, while about a
      quarter (26.9%) routinely counsel women about ECP use. About 21% of respondents
      currently use EC. Logistic regression analysis revealed significant results for
      gender [odds ratio (OR) =3.64; 95% confidence interval (CI) OR = 1.31-10.01),
      religion (OR = 0.26; 95% CI OR = 0.11-0.630) and marital status (OR = 0.19; 95%
      CI = 0.07-0.56). CONCLUSION: The correct knowledge and professional disposition
      toward EC as a form of contraception is low. We recommend that in-service
      training should focus more on EC to improve the quality of their knowledge and
      attitude towards it.

PMID- 24909466
TI  - Management of the mass casualty from the 2001 Jos crisis.
AB  - BACKGROUND: We report our experience in the hospital management of mass casualty
      following the Jos civil crisis of 2001. MATERIALS AND METHODS: A retrospective
      analysis of the records of patients managed in the Jos civil crisis of September
      2001, in Plateau State, Nigeria. Information extracted included demographic data
      of patients, mechanisms of injury, nature and site of injury, treatment
      modalities and outcome of care. RESULTS: A total of 463 crisis victims presented
      over a 5 day period. Out of these, the records of 389 (84.0%) were available and
      analyzed. There were 348 (89.5%) males and 41 females (10.5%) aged between 3
      weeks and 70 years, with a median age of 26 years. Most common mechanisms of
      injury were gunshot in 176 patients (45.2%) and blunt injuries from clubs and
      sticks in 140 patients (36.0%). Debridement with or without suturing was the most
      common surgical procedure, performed in 128 patients (33%) followed by
      exploratory laparotomy in 27 (6.9%) patients. Complications were documented in 55
      patients (14.1%) and there were 16 hospital deaths (4.1% mortality). Challenges
      included exhaustion of supplies, poor communication and security threats both
      within the hospital and outside. CONCLUSION: Most patients reaching the hospital
      alive had injuries that did not require lifesaving interventions. Institutional
      preparedness plan would enable the hospital to have an organized approach to
      care, with better chances of success. More effective means of containing crises
      should be employed to reduce the attendant casualty rate.

PMID- 24909467
TI  - Risks associated with subsequent pregnancy after one caesarean section: A
      prospective cohort study in a Nigerian obstetric population.
AB  - CONTEXT: Aversion for cesarean delivery is common in our practice and risks
      associated with caesarean section may contribute to this phenomenon. OBJECTIVE:
      The objective of this study was to estimate the risks associated with subsequent
      pregnancies in women with one previous cesarean section in a low resource
      setting. SETTING AND DESIGN: A prospective cohort study carried out at two major
      tertiary maternity centers in Enugu. MATERIALS AND METHODS: Maternal and
      perinatal outcomes were compared between women with one previous caesarean and
      women who had only previous vaginal deliveries. STATISTICAL ANALYSIS USED:
      Analysis was performed with SPSS statistical software version 17.0 for windows
      (IBM Incorporated, Armonk, NY, USA) using descriptive and inferential statistics
      at 95% of the confidence level confidence. RESULTS: A total of 870 women were
      studied. These were divided into 435 cases and 435 controls. The absolute risk of
      cesarean section in a subsequent pregnancy in women with one previous cesarean
      was 75.8% (95% confidence interval [CI]: 72.0, 80.0). Cesarean section was
      significantly commoner in women with one previous cesarean compared with those
      who had previous vaginal delivery (Relative risk [RR] =3.78; 95% CI: 1.8, 6.2).
      Placenta praevia (RR = 5.0; 95% CI: 2.6, 7.2.), labor dystocia (RR = 6.4, 95% CI:
      3.2, 11.2) intrapartum hemorrhage (RR = 5.0, 95% CI: 2.1, 9.3) primary postpartum
      hemorrhage (RR = 5.0, 95% CI: 1.5, 4.3.), blood transfusion (RR = 6.0, 95% CI:
      3.4, 10.6) and Newborn special care admission (RR = 2.5; 95% CI: 1.1, 4.9) were
      significantly more common in women with one previous cesarean compared with those
      with previous vaginal deliveries. The absolute risk of failed trial of vaginal
      birth after a cesarean was 45% (95% CI: 38.5, 51.5). CONCLUSION: Women who have
      one previous C-section face a markedly increased risk of repeat caesarean
      sections and feto-maternal complications in subsequent pregnancies. There is a
      need for doctors in Nigeria to be mindful of these risks while offering primary
      cesarean section in this low resource setting.

PMID- 24909468
TI  - The effects of dexamethasone and metoclopramide on early and late postoperative
      nausea and vomiting in women undergoing myomectomy under spinal anaesthesia.
AB  - BACKGROUND: Post-operative nausea and vomiting (PONV); early or late, has
      detrimental effects on surgical patients such as surgical wound disruption,
      esophageal tear and delayed discharge from the post anesthetic care unit. This
      study evaluated the effects of dexamethasone-metoclopramide (DM) in the
      prevention of early and late PONV in women undergoing myomectomy under
      subarachnoid block. MATERIALS AND METHODS: Following approval from the Research
      and Ethics Committee of the Hospital, informed consent was obtained from each
      prospective patient. Patients were randomly allocated to either the DM group,
      metoclopramide only (MO) group or dexamethasones only (DO) group using the
      computer-generated random numbers in sealed envelopes. Immediately after the
      induction of spinal anesthesia, the DM group received intravenous (i.v.)
      dexamethasone 8 mg and metoclopramide 10 mg, the MO group received metoclopramide
      10 mg i.v and the DO group received dexamethasone 8 mg i.v. The incidence of
      early and late PONV formed the primary outcome. RESULTS: A total of 90 patients,
      with aged range between 21-64 years were studied. Dexamethasone alone group had
      the highest incidence of 40% for early but no for late PONV ( P = 0.003)
      Metoclopramide alone group had an incidence of 29.97% for early PONV and 26.6%
      for late PONV. There was reduced incidence of both early and late PONV in the DM
      group, but of lesser magnitude than DO or MO respectively. CONCLUSION:
      Dexamethasone protects against the incidence of late PONV with a minimal effect
      on early PONV. The combination of dexamethasone and metoclopramide had comparable
      effect on both and of better magnitude than metoclopramide alone.

PMID- 24909469
TI  - Intubation without muscle relaxation for suspension laryngoscopy: a randomized,
      controlled study.
AB  - OBJECTIVE AND AIM: The objective of the following study is to examine the
      effectiveness and safety of suspension laryngoscopy under intubation with
      propofol and remifentanil alone for vocal fold nodule (VFN) excision. MATERIALS
      AND METHODS: A total of 40 patients were equally and randomly assigned to
      elective VFN excision using suspension laryngoscopy under intubation with
      propofol and remifentanil alone (Group A) or with supplementary cisatracurium
      (Group B). RESULTS: Intubation time was significantly longer in Group A than in
      Group B (300.0 +/- 30.0 s vs. 265.2 +/- 38.7 s, P = 0.003). The two groups showed
      similar Cormack-Lehane classifications, intubation conditions and ease of
      suspension laryngoscopy. Both groups showed favorable cardiopulmonary safety
      profiles. Post-anesthesia recovery was significantly more rapid in Group A than
      in Group B, in terms of times to spontaneous breathing return (7.2 +/- 1.4 min
      vs. 10.9 +/- 1.6 min, P < 0.001), consciousness return (7.4 +/- 1.5 min vs. 12.3
      +/- 1.8 min, P < 0.001), removal of tracheal intubation (8.1 +/- 1.5 min vs. 13.2
      +/- 1.7 min, P < 0.001) and operating room discharge (12.7 +/- 1.4 min vs. 22.1
      +/- 1.3 min, P < 0.001). CONCLUSION: Use of propofol and remifentanil alone
      provides favorable intubation and anesthesia conditions for suspension
      laryngoscopic VFN excision and accelerates post-anesthesia recovery.

PMID- 24909470
TI  - Incidence and risk factors for retinal vein occlusion at the University of Port
      Harcourt Teaching Hospital, Port Harcourt, Nigeria.
AB  - OBJECTIVE: The objective of the following study is to determine the incidence of
      retinal vein occlusion (RVO) and identify the risk factors in RVO in patients
      presenting to a tertiary hospital in Rivers State. MATERIALS AND METHODS: The
      medical records of consecutive patients with RVO who presented to the retina
      clinic of the eye Department of University of Port Harcourt Teaching Hospital
      over a 5 year period were retrieved. Information extracted from the data included
      the demographic data of patients, presenting visual acuity, history of systemic
      and ocular disease, blood pressure and intraocular pressure. Data was analyzed
      using the Statistical Package for Social Sciences 20.0. (IBM Corporation and its
      licensors 1989,2011). RESULTS: Out of the 364 patients seen at the retina clinic
      during this period, 27 (7.4%) had RVO. Seven patients had bilateral disease. The
      incidence of RVO in the retinal clinic was 7.4%. Systemic hypertension, diabetes
      mellitus, hyperlipidemia and glaucoma were the main risk factors recorded in our
      patients. Central retinal vein occlusion (CRVO) 20 (74%) was more predominant
      than branch retinal vein occlusion (BRVO) 7 (26%). 21 eyes of patients with CRVO
      had visual acuities of < 3/60, while 7 eyes of patients with BRVO had visual
      acuities less than 3/60. Vitreous hemorrhage 10 (52.6%) was the most common
      complication encountered. All cases of non-perfused vein occlusion 4 (14.8%) were
      seen in patients who had CRVO. CONCLUSION: The incidence of RVO in our hospital
      is high. RVO is a significant cause of visual impairment, with CRVO being more
      common. Identifying associated risk factors and treating these could help reduce
      the incidence of RVO.

PMID- 24909471
TI  - Refractive errors in children with autism in a developing country.
AB  - BACKGROUND: In a resource-limited country visual problems of mentally challenged
      individuals are often neglected. AIM: The present study aims to study refractive
      errors in children diagnosed with autism in a developing country. MATERIALS AND
      METHODS: Ophthalmic examination was carried out on children diagnosed with autism
      attending a school for the mentally challenged in Enugu, Nigeria between December
      2009 and May 2010. Visual acuity was assessed using Lea symbols. Anterior and
      posterior segments were examined. Cycloplegic refraction was performed. Data was
      entered on the protocol prepared for the study and analyzed using Statistical
      Package for the Social Sciences version 17 (Chicago IL, USA). RESULTS: A total of
      21 children with autism were enrolled in the school; 18 of whom were examined
      giving coverage of 85.7%. The age range was 5-15 years, with a mean of 10.28
      years (standard deviation +/- 3.20). There were 13 boys and 5 girls. One child
      had bilateral temporal pallor of the disc and one had bilateral maculopathy with
      diffuse chorioretinal atrophy. Refraction revealed 4 children (22.2%) had
      astigmatism and 2 children (11.1%) had hypermetropia. CONCLUSION: Significant
      refractive error mainly astigmatism was noted in the children with autism.
      Identifying refractive errors in these children early and providing appropriate
      corrective lenses may help optimize their visual functioning and impact their
      activities of daily life in a positive way.

PMID- 24909472
TI  - Knowledge and attitudes of Turkish endodontists towards digital radiology and
      cone beam computed tomography.
AB  - INTRODUCTION: The aim of this study was to assess the knowledge and attitudes of
      Turkish endodontists toward digital radiological imaging (DRI) and cone-beam
      computed tomography (CBCT). MATERIALS AND METHODS: One hundred and fifty
      questionnaires were distributed. Questionnaires were given to a sample of
      endodontists and PhD students in endodontics who attended the 11 th International
      Congress of the Turkish Endodontic Society in Istanbul in 2012. Following the
      congress, the same questionnaires were sent electronically to endodontists who
      did not attend the congress. The participants were asked to answer 28 multiple
      choice questions concerning their knowledge and practice regarding recent imaging
      techniques. The questions were subdivided into 2 main topics; general
      information; general approach to digital imaging. The statistical analysis was
      carried out by an chi2-test to compare the means at a significance level of P <
      0.05. RESULTS: The response rate for this study was 74%. The mean age of the
      endodontists who participated in this study was 32.74 +/- 10.40 (range 22-61
      years). Of the endodontists, 76.6% used digital imaging techniques (DUEs) in
      their clinics. Statistically significant differences were found between the DUEs
      and endodontists not using digital imaging (NDUEs), regarding age, gender,
      graduation year and place of employment ( P < 0.01). Endodontists 40-years-old
      and above had significantly lower knowledge of CBCT compared to the younger
      groups ( P = 0.001). CONCLUSIONS: The number of endodontists using digital
      imaging has been increasing in Turkey. The findings of the present study
      highlighted the need for adapting to new technologies via continuing education.

PMID- 24909473
TI  - Outcomes of surgical management of intestinal atresias.
AB  - BACKGROUND: Outcome of managing intestinal atresias has improved in many
      developed countries, but most reports from low and middle income countries
      (LMICs) still show high morbidity and mortality. OBJECTIVE: The objective of the
      following study is to evaluate the outcome of surgically managed intestinal
      atresias in our health resource-limited setting. PATIENTS AND METHODS: All cases
      of intestinal atresias managed surgically from July 2007 to July 2012 were
      retrospectively analyzed. RESULTS: There were 23 patients comprised of 11 males
      and 12 females; 10 duodenal atresias (DA), 13 jejunoileal atresias (JIA) and no
      colonic atresias. The mean age at presentation to the surgeon was 10.3 days
      (range 2-43 days) for JIA and 10.6 days (range 1-35 days) for DA. Average weight
      at presentation was 2.2 kg for JIA and 2.4 kg for DA. Mean duration from
      presentation to surgery was 3.4 days for JIA and 4.8 days DA. All the JIA had
      primary repair; type 1 DA had duodenotomy and web excision while others had
      diamond duodenoduodenostomy. However one DA had duodenojejunostomy. 7 out of 10
      DA patients (70%) had at least one associated anomaly, the most common being
      annular pancreas. There were 4 re-operations in JIA and none in DA (17.4%
      reoperation rate for 3 anastomotic leaks, 1 anastomotic stricture). Average
      hospital stay was 23 days for JIA and 12.3 days for DA. Overall, 5 (5) patients
      died (2 JIA and 3 DA) giving a mortality rate of 21.7%. Mortality rate for DA is
      30% while for JIA is 15.4%. Causes of death were: Sepsis with disseminated
      intravascular coagulation (1), sepsis from anastomotic leakage (1), septic shock
      (1), anesthesia-related (1), undetermined (1). Two of the mortalities (40%) had
      re-operation for anastomotic leak. CONCLUSIONS: Short-term survival of neonates
      with intestinal atresias in our unit is still poor when compared with statistics
      from developed countries. Late presentation is common in this series, but does
      not appear to have negatively affected outcome. A high proportion of the
      mortalities had reoperation for anastomotic leak.

PMID- 24909474
TI  - Sonographic assessment of the normal limits of the spleen in healthy school
      children in South-East Nigeria.
AB  - BACKGROUND/OBJECTIVE: Ultrasonogrphy is a good modality for the detection of
      splenomegaly even when it is not clinically palpable. The objective of this study
      was to establish the normal values of splenic length in healthy school children
      in South-East, Nigeria and to correlate them with body indices. MATERIALS AND
      METHODS: This is a cross-sectional prospective study of 1315 children (633 boys
      and 682 girls) between the ages of 5 and 17 years. The splenic length was
      measured between the most superiomedial and the most inferiolateral margins, at
      the level of the hilum. Only the spleens that had normal shape and echotexture
      were measured. The mean splenic length and the 5 th and 95 th percentiles were
      determined for each age. The length was correlated with the sex, age, weight
      (WT), height, body mass index (BMI) and body surface area (BSA) of the subjects.
      A regression model for prediction of spleen dimension from age and body habitus
      was computed. RESULTS: There was a significant correlation between splenic length
      and age, P < 0.001. Males had statistically significant longer spleen length than
      females. The splenic length correlated best with BSA, followed by body WT and
      least with BMI. CONCLUSIONS: This study noted racial variation between the
      established Nigerian values and results from other countries of the world. For
      the first time, a baseline value for splenic size for the Nigerian Children of
      various ages has been established with a regression model for predicting the
      splenic sizes.

PMID- 24909475
TI  - Maternal understanding of fetal movement in third trimester: a means for fetal
      monitoring and reducing stillbirth.
AB  - BACKGROUND: Fetal movement, a sign of life, is widely considered as an indicator
      of fetal health status. Therefore, perceived alteration in regular fetal movement
      after the age of viability may signify impending adverse perinatal outcome. AIMS:
      This study aimed to determine maternal knowledge, behavior, and concerns about
      abnormal fetal movement in the third trimester of pregnancy. MATERIALS AND
      METHODS: A total of 225 women were surveyed using a self-administered
      questionnaire at the out-patient prenatal clinics of two tertiary health
      facilities in Nigeria between December 1, 2012 through January 31, 2013.
      Questions addressed knowledge, perception behavior, and concerns about experience
      of abnormal fetal movement. RESULTS: Correct Knowledge of excessive and decreased
      fetal movement was found in 47% and 31.1% of respondents, respectively. Majority
      of women (87.6%) either had no knowledge of normal parameters of fetal activity
      or did not recall being told that movement frequency and strength should increase
      in the third trimester. The proportion of women who expressed concern over
      excessive and decreased fetal movement was 31.1% and 21.8%, respectively.
      Maternal education was significantly associated with correct knowledge of
      decreased fetal movement ( P = 0.026). Almost 36% of respondents had knowledge of
      at least one potential consequence of abnormal fetal movement. CONCLUSION:
      Maternal educational level is an important factor in the early identification of
      abnormality of fetal movement. The unsatisfactory knowledge and poor perception
      behavior among respondents reflect the need for a guideline, particularly during
      antenatal care, on information and management of abnormal fetal movement in our
      setting to prevent avoidable stillbirth.

PMID- 24909476
TI  - Effectiveness of a structured checklist of risk factors in identifying pregnant
      women at risk of gestational diabetes mellitus: a cross-sectional study.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased risk
      of mortality and morbidity for pregnant women and newborns. Identifying pregnant
      women with risk factors for GDM based on the clinical suspicion is a popular
      approach. However, the effectiveness of the use of a structured checklist of risk
      factors is yet to be evaluated. This study assessed the effectiveness of a
      structured checklist of risk factors in identifying pregnant women at risk of GDM
      at the University College Hospital, Ibadan. MATERIALS AND METHODS: It was a
      comparative cross-sectional study implemented in two phases. The first phase
      (Group A) of the study was a prospective study that involved 530 pregnant women
      who presented at the booking clinic. A structured checklist containing risk
      factors was used to identify women at the risk of GDM. The second phase (Group B)
      was a retrospective study of 530 pregnant women managed 2 years previously who
      were selected by systematic random technique. RESULTS: The mean age, gestational
      age at booking, gestational age at delivery and birth weight were 30.2 +/- 5.2
      years, 21 +/- 10.8 weeks, 38.7 +/- 2.7 weeks and 3.1 +/- 0.7 kg respectively. The
      prevalence of GDM in Group A and B were 4.9% and 1.6% respectively ( P < 0.05).
      There was about three fold increase in identification of women at risk of GDM by
      use of a checklist. CONCLUSION: Identification of women at risk of GDM was
      approximately 3-4 fold higher with the use of checklist of risk factors.
      Exhaustive clinical identification with a checklist of risk factors for GDM
      should be encouraged.

PMID- 24909477
TI  - Day surgery: are we transferring the burden of care?
AB  - CONTEXT: Day procedures are preferred by many surgeons for minor and intermediate
      procedures in fit patients. It is however considered to transfer the burden of
      care to care-givers and other healthcare providers. AIM: The aim of the following
      study is to assess the tendency of day care patients seeking attention from
      health care providers and their ability to ambulate in the first week. SETTINGS
      AND DESIGN: Prospective study in a tertiary health facility in South-South
      Nigeria. MATERIALS AND METHODS: Patients in American Society of Anesthesiologists
      class I and II undergoing day-care procedures in a surgery unit were assessed at
      one week for the effects of the procedure on ambulation and their likelihood to
      seek medical attention. Data on the sex, type of procedure, pain, bleeding and
      ambulation was analyzed. A visual analog pain score of 0- 3 (mild); 4-6
      (moderate) and 7-10 (severe) was used. Bleeding was defined as complete soaking
      of the two-layered gauze dressing with blood. STATISTICAL ANALYSIS: Analysis was
      performed with SPSS 17 for Windows (SPSS Inc. Chicago, Illinois) and presented as
      percentages, mean and tables. RESULTS: A total of 99 patients comprised of 47
      males and 52 females registered in the study; with a mean age of 38 years (range
      16-70); 76 patients (77%) complained of pain at the operation site while 23 (23%)
      had no complaints. Pain was mild in 59 (78%) and moderate 17 (22%). None had
      severe pain or bleeding from the operation site; 85 patients (86%) could ambulate
      easily, 14 (14%) partially and none completely unable to ambulate. CONCLUSION:
      Day procedures in selected patients has minimal affects on their ambulation and
      no increased risk of seeking medical attention in the first week and would appear
      not to transfer the burden of care to the community.

PMID- 24909478
TI  - Caregivers' willingness-to-pay for a topical anesthetic cream for minor medical
      procedures in children.
AB  - BACKGROUND: Topical anesthetic cream (TAC) is not in use in pediatric practice in
      Sub-saharan regions. Knowledge of Caregivers' willingness-to-pay (WTP) for the
      cream is necessary for its deployment. OBJECTIVE: To determine the WTP for TAC
      for minor pediatric painful procedures. MATERIALS AND METHODS: The study was a
      questionnaire-based conducted in two tertiary health institutions in southeast
      Nigeria. WTP was elicited using the contingent valuation method. The respondents
      were caregivers to children that attended out-patient clinics and in-patient.
      Data analysis was by Statistical Package for the Social Sciences software (SPSS)
      and STATA11. RESULTS: Majority (94%) of the respondents were willing to pay for
      TAC. The mean maximum WTP was US$8.31. Multivariate analysis showed no
      statistically significant association between many variables with WTP for TAC.
      CONCLUSIONS: Their average WTP was higher than the market price of topical
      anesthetic cream. Therefore, there is a good prospect for TAC if deployed in
      Nigeria.

PMID- 24909479
TI  - Clinical and laboratory experience of chorionic villous sampling in Nigeria.
AB  - BACKGROUND: Chorionic villous sampling is a first trimester invasive diagnosis
      procedure that was introduced in Nigeria < 2 decades ago. OBJECTIVE: The
      objective of the following study is to review experience with chorionic villous
      sampling in relation to clinical and laboratory procedures, including general
      characteristics of women, indications and outcome, complications, laboratory
      analysis and learning curve. MATERIALS AND METHODS: Descriptive study of
      chorionic villous samplings between 2005 and 2012. Clinical and laboratory data
      were extracted from records. The women had trans-abdominal or trans-cervical
      procedure after counseling. Deoxyribonucleic acid extraction was by boiling
      method and molecular diagnosis by restriction fragment length polymorphism or
      quantitative fluorescence polymerase chain reaction. Analyzed data were presented
      using simple frequency tables. RESULTS: A total of 426 women were analyzed. The
      major indications were Sickle cell anemia (97.2%), gender determination (1.9%)
      and aneuploidy (0.7%) respectively. Most procedures (71.2%) were done between 11
      +0 and 13 +6 weeks by trans-abdominal approach (88.7%). Overall success at the
      first sampling was 98.8%. Error in laboratory diagnosis recorded in 3 (0.7%)
      pregnancies, while 5 (1.2%) were reanalyzed due to maternal decidua/inadequate
      fetal sample (0.7%) or failure of amplification (0.5%) respectively. Primary sex
      ratio was 5 (XY): 3 (XX). Down syndrome was the most common aneuploidy diagnosed
      with a detection rate of 66.7%. Learning curve was evident from reducing the
      incidence of abortion, number of aspirations and increasing success at the first
      attempt and villi yield. CONCLUSION: The present study shows acceptance and
      utilization of chorionic villus sampling and also demonstrates its safety and
      reliability.

PMID- 24909480
TI  - The relationship between serum bilirubin level with interleukin-6, interleukin-10
      and mortality scores in patients with sepsis.
AB  - CONTEXT: Bilirubin has been shown to influence the mechanisms of both apoptosis
      and inflammation. AIMS: The aim of the following study is to investigate the
      relationship between the serum bilirubin level with sepsis progression. SETTINGS
      AND DESIGN: A total of 20 patients from intensive care unit were included for
      this study. MATERIALS AND METHODS: Patients were divided into two groups:
      Patients diagnosed with sepsis according to the American College of Chest
      Physicians/Society of Clinical Care Medicine consensus conference criteria (n0 =
      10) and patients treated for various other diagnoses ( n = 10). Blood samples
      were collected for both groups at the time of origin (defined as the time of
      diagnosis) and 24 and 48 h after diagnosis. Serum interleukin (IL)-6, IL-10 and
      bilirubin levels were analyzed and compared. Acute physiology and chronic health
      evaluation (APACHE) II and sepsis related organ failure (SOFA) scores of the
      patients were also evaluated. STATISTICAL ANALYSIS USED: We used Statistical
      Package for Social Sciences (SPSS for Windows, version 17.0, SPSS Inc. 233 South
      Wacker Drive, Chicago) for statistical analysis. RESULTS: At all-time intervals,
      serum IL-6, IL-10 and total, direct and indirect serum bilirubin levels were
      significantly higher in the sepsis group ( P < 0.05); APACHE II and SOFA scores
      were also significantly higher. Both SOFA scores and serum IL-10 levels were
      positively correlated with bilirubin levels 24 h after diagnosis (P < 0.05, r = 
      0.76). CONCLUSIONS: Although levels of bilirubin and other associated parameters
      were higher for the sepsis group, only SOFA score and bilirubin levels were
      correlated. Because bilirubin is already a SOFA parameter, this correlation was
      not considered as clinically significant.

PMID- 24909481
TI  - The effect of anesthesia type on stress hormone response: comparison of general
      versus epidural anesthesia.
AB  - AIM: The aim of this study was to investigate the effect of different types of
      anesthesia on stress hormones. MATERIALS AND METHODS: The study was included 60
      ASAI-II cases scheduled for major lower extremity surgery. The cases were
      randomized into 2 groups: The EA group was administered epidural anesthesia and
      the GA group was administered standard general anesthesia. In order to evaluate
      the surgical trauma - related stress response, CRP, TSH, cortisol, and fasting
      blood sugar(FBS) levels were measured preoperatively, 30 min after surgical
      incision, and 24 h post surgery. RESULTS: Between-group comparisons; Preoperative
      values were not significantly different between the groups.( P > 0,05) Pulse rate
      and cortisol values significantly higher in general group at 30 min. ( P < 0,05),
      and the FBS values were significantly higher in the epidural group at 24 h.( P <
      0,05) There were not found differences for other parameters at evaluation times.
      CONCLUSION: No differences were observed between the two anesthesia methods, in
      terms of minimizing the stress response due to surgical trauma during major low
      extremity surgery.

PMID- 24909482
TI  - Multidisciplinary approach for the rehabilitation of central giant cell
      granuloma: a clinical report.
AB  - The central giant cell granuloma (CGCG) is benign, nonodontogenic, and
      intraosseous lesion of the jaw. Aggressive subtypes of CGCG have a tendency to
      recur after excision and require wide resection that leads to major defects in
      the jaw. In this case report a patient who had severe mandibular bony deficiency
      as a result of excision of aggressive CGCG, orthodontic, and prosthetic treatment
      was described. The defect was reconstructed with iliac bone graft. Four years
      later vertical distraction osteogenesis was performed on the grafted mandible in
      order to obtain a satisfactory bony height of mandibular ridge. After healing
      period three endosseous dental implants were placed to grafted region. Because of
      pubertal growth stage, a hybrid removable denture was constructed. The
      construction of a hybrid removable denture markedly improved the patient's
      speech, mastication, and appearance. After pubertal growth stage, a fixed partial
      denture construction was planned and future parts of treatment procedures were
      described to the patient. Distraction osteogenesis and endosseous dental implants
      can be a good alternative method for the unsatisfactory reconstructions of
      mandibular deficiencies. 

PMID- 24909483
TI  - Pulmonary artery thrombosis in a patient with right-sided heart failure.
AB  - Pulmonary thromboembolism occurring either abruptly or insidious poses a greater
      challenge in diagnosis. A high index of suspicion is required to proceed with
      proper investigations in patients with nonspecific cardiac or respiratory
      presentation to make the diagnosis of pulmonary embolism (PE). Early diagnosis of
      PE with prompt initiating of anticoagulation therapy has been proven to have a
      positive impact in mortality reduction associated with recurrent episodes of this
      condition. We present a case of a 76-year-old man, known to have cardiac failure
      on regular treatment who presented with predominant features of right-sided heart
      failure accompanied with dizziness. He was diagnosed to have pulmonary artery
      thrombosis by computerized tomography. Anticoagulation therapy was initiated with
      marked clinical improvement.

PMID- 24909484
TI  - Phthiriasis palpebrarum misdiagnosed as allergic blepharoconjunctivitis in a 6
      year-old girl.
AB  - Phthiriasis palpebrarum is an infestation of the eyelashes caused by the louse
      Pthirus pubis (Linnaeus, 1758). We report a case of phthiriasis palpebrarum in a
      6-year-old girl, which was initially misdiagnosed as allergic
      blepharoconjunctivitis. Parasites and their nits were found adhering to the
      eyelashes and eyelids of her right eye as well as scalp hairs. No abnormality was
      found in the left eye. The histopathology exam revealed the presence of adults
      and eggs of Pthirus pubis. We mechanically removed all the eyelashes of the right
      eye at their base, with lice and nits. The scalp was shaved and washed with
      phenothrin shampoo. No recurrence was found during 3 months of follow-up. Removal
      of the eyelashes, cutting of scalp hairs, and phenothrin shampoo may be effective
      in treating phthiriasis palpebrarum. In cases of blepharoconjunctivitis, eyelids
      and eyelashes should be carefully examined by slit lamp to avoid misdiagnosis. 

PMID- 24909485
TI  - Case series on tropical diabetic hand syndrome.
AB  - Tropical diabetic hand syndrome is a term used to describe diabetes complication
      of the hand affecting people in the tropics. It consists of localized cellulitis
      with variable swelling and ulceration of the hands, progressive, fulminant hand
      sepsis and gangrene in extreme cases. This syndrome is not well-recognized and is
      therefore less frequently reported. The authors describe three different female
      patients who were known diabetics of varying duration presenting with this
      syndrome at our tertiary health center and who were successfully managed by both
      the surgical and medical units. The need for early diagnosis and aggressive
      management is emphasized. 

PMID- 24909486
TI  - Complications after transoral excision in previously irradiated head and neck
      cancer patients: our experience in a retrospective cohort study of fifty-two
      patients.

PMID- 24909487
TI  - The effect of magnesium supplements on early post-transplantation glucose
      metabolism: a randomized controlled trial.
AB  - Post-transplantation hypomagnesemia is common and predicts diabetes. Magnesium
      improves glycemic control in diabetics and insulin sensitivity in insulin
      resistant subjects. We aimed to assess the effectiveness of oral magnesium for
      improving glycemic control and insulin sensitivity at 3 months post
      transplantation. We conducted a single-center, open-label, randomized parallel
      group study. We included adults with serum magnesium <1.7 mg/dl within 2 weeks
      after kidney transplantation. We randomized participants to 450 mg magnesium
      oxide up to three times daily or no treatment. The primary endpoint was the mean
      difference in fasting glycemia. Secondary endpoints were the mean difference in
      area under the curve (AUC) of glucose during an oral glucose tolerance test and
      insulin resistance measured by Homeostasis Model of Assessment-Insulin Resistance
      (HOMA-IR). Analyses were on intention-to-treat basis. In patients randomized to
      magnesium oxide (N = 27) versus no treatment (N = 27), fasting glycemia on
      average was 11.5 mg/dl lower (95% CI 1.7 to 21.3; P = 0.02). There was no
      difference between the two groups neither for 2 h AUC, where the mean value was
      1164 mg/dl/min (95% CI -1884 to 4284; P = 0.45) lower in the treatment group nor
      for HOMA-IR. Magnesium supplements modestly improved fasting glycemia without
      effect on insulin resistance. Higher baseline glycemia among patients in the
      control group may have driven the positive outcome (ClinicalTrials.gov number:
      NCT01889576). 

PMID- 24909488
TI  - The light-induced FOS response in melanopsin expressing HEK-293 cells is
      correlated with melanopsin quantity and dependent on light duration and
      irradiance.
AB  - We established a cell line (HEK-hMel) expressing melanopsin in a tetracycline
      dependent manner to elucidate new aspects of melanopsin's light response.
      Different light stimuli were evaluated using FOS expression as response
      parameter. Immunoblotting was used to evaluate expression of melanopsin and FOS
      and qPCR to quantify FOS mRNA responses. The magnitude of the FOS response was
      found to correlate with the amount of melanopsin expressed by the cells, and a
      transient FOS mRNA induction followed by FOS protein still elevated after 24 h of
      illumination was revealed. Exposing the cells to darkness after light resulted in
      reduction of the response compared to exposure to light solely showing dependency
      on continuous light. Increasing irradiances of blue light (480 nm) up to 10(11)
      quanta cm(-2)  s(-1) elicited steep increases in FOS mRNA, while increases
      between 10(12) and 5 * 10(13) quanta  cm(-2)  s(-1) resulted in equally high FOS
      expression. The HEK-hMel cells were used to characterize facets of melanopsin's
      light-induced FOS response not approachable in vivo. Novel information such as
      dependency of the FOS response on both melanopsin amount and light intensity in
      addition to a detailed time-course of both FOS mRNA and protein were revealed. 

PMID- 24909490
TI  - A case of Mycobacterium sherrisii pneumonia diagnosed by PCR/ESI-MS method.
AB  - Mycobacterium sherrisii is an acid fast organism that is recently validated as a
      novel species. It is recognized to cause severe disease in immunosuppressed
      individuals especially in patients with HIV. We describe a case M. sherrisii
      pneumonia which was diagnosed using PCR coupled with electrospray ionization mass
      spectrometry (PCR/ESI-MS) technology. 

PMID- 24909489
TI  - Emergence of SCCmec type III with variable antimicrobial resistance profiles and
      spa types among methicillin-resistant Staphylococcus aureus isolated from
      healthcare- and community-acquired infections in the west of Iran.
AB  - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of
      public health importance. The prevalence of MRSA and its antimicrobial resistance
      pattern, as well as SCCmec and spa types, remain unclear both in the community
      and in the hospitals of the western region of Iran. METHODS: One hundred MRSA
      isolates were collected from different hospitals in the west of Iran during 2010
      2011. Antimicrobial susceptibility testing to 15 antimicrobial agents was carried
      out by disk agar diffusion (DAD) method in accordance with the Clinical and
      Laboratory Standards Institute guidelines. Vancomycin minimum inhibitory
      concentrations (MICs) were evaluated by a broth microdilution method. The Etest
      was used for the detection of highly gentamicin-resistant MRSA. A combination of
      single and multiplex PCR was used for the detection of different resistance
      genes, including beta-lactamase, aminoglycoside modifying enzymes (AMEs), and
      macrolide-lincosamine, and for SCCmec typing of MRSA isolates. Genotyping of MRSA
      isolates was performed via spa typing. RESULTS: All tested isolates were
      susceptible to quinupristin-dalfopristin, linezolid, and vancomycin, but were
      resistant to penicillin (100%), erythromycin (50%), clindamycin (27%), and
      gentamicin (18%). MIC50 and MIC90 was 256 MUg/ml among gentamicin-resistant MRSA.
      The most prevalent AME genes among aminoglycoside-resistant isolates were aac(6')
      1e-aph(2")-1a (77.8%), aph(3')-IIIa (38.9%), and ant(4')-1a (27.8%). Nearly all
      tetracycline- and erythromycin-resistant MRSA had ermA and/or ermC but not ermB.
      Five SCCmec types and subtypes, 13 spa types, and four BURP groups (A-D) were
      identified. SCCmec types III (45%) and IVc (24%), spa type t701 (30%), and new
      spa type t12311 (15%) were the most prevalent among MRSA isolates. CONCLUSIONS:
      This study showed the emergence of MRSA with SCCmec type III and with spa types
      t12311, t10740, t1234, t1991, and t2651 with different phenotypic and genotypic
      antimicrobial resistance in the west of Iran. We found different SCCmec and spa
      types distributed among nosocomial and non-nosocomial MRSA in the west of Iran.

PMID- 24909491
TI  - Coincidentally, this first issue marks the 50th anniversary of the seminal
      discovery of the excision-repair of damaged DNA. Preface.

PMID- 24909492
TI  - Evaluation of using spot urine to replace 24 h urine sodium and potassium
      excretions.
AB  - OBJECTIVE: The most accurate method to estimate Na and K intakes is to determine
      24 h urinary excretions of these minerals. However, collecting 24 h urine is
      burdensome. Therefore it was studied whether spot urine could be used to replace
      24 h urine samples. DESIGN: Participants collected 24 h urine and kept one
      voiding sample separate. Na, K and creatinine concentrations were analysed in
      both 24 h and spot urine samples. Also 24 h excretions of Na and K were predicted
      from spot urine concentrations using the Tanaka and Danish methods. SETTING: In
      2011 and 2012, urine samples were collected and brought to the study centre at
      Wageningen University, the Netherlands. SUBJECTS: Women (n 147) aged 19-26 years.
      RESULTS: According to p-aminobenzoic acid excretions, 127 urine collections were
      complete. Correlations of Na:creatinine, K:creatinine and Na:K between spot urine
      and 24 h urine were 0.68, 0.57 and 0.64, respectively. Mean 24 h Na excretion
      predicted with the Tanaka method was higher (difference 21.2 mmol/d, P<0.001)
      than the measured excretion of 131.6 mmol/d and mean 24 h Na excretion predicted
      with the Danish method was similar (difference 3.2 mmol/d, P=0.417) to the
      measured excretion. The mean 24 h K excretion predicted with the Tanaka method
      was higher (difference 13.6 mmol/d, P<0.001) than the measured excretion of 66.8
      mmol/d. Bland-Altman plots showed large individual differences between predicted
      and measured 24 h Na and K excretions. CONCLUSIONS: The ratios of Na:creatinine
      and K:creatinine in spot urine were reasonably well associated with their
      respective ratios in 24 h urine and appear to predict mean 24 h Na excretion of
      these young, Caucasian women.

PMID- 24909494
TI  - Evolutionary prisoner's dilemma game on graphs and social networks with external
      constraint.
AB  - A game-theoretical model is constructed to capture the effect of external
      constraint on the evolution of cooperation. External constraint describes the
      case where individuals are forced to cooperate with a given probability in a
      society. Mathematical analyses are conducted via pair approximation and diffusion
      approximation methods. The results show that the condition for cooperation to be
      favored on graphs with constraint is b-/c->k/A- (A-=1+kp/(1-p)), where b- and c-
      represent the altruistic benefit and cost, respectively, k is the average degree
      of the graph and p is the probability of compulsory cooperation by external
      enforcement. Moreover, numerical simulations are also performed on a repeated
      game with three strategies, always defect (ALLD), tit-for-tat (TFT) and always
      cooperate (ALLC). These simulations demonstrate that a slight enforcement of ALLC
      can only promote cooperation when there is weak network reciprocity, while the
      catalyst effect of TFT on cooperation is verified. In addition, the interesting
      phenomenon of stable coexistence of the three strategies can be observed. Our
      model can represent evolutionary dynamics on a network structure which is
      disturbed by a specified external constraint.

PMID- 24909493
TI  - Global sensitivity analysis of a mathematical model of acute inflammation
      identifies nonlinear dependence of cumulative tissue damage on host interleukin-6
      responses.
AB  - The precise inflammatory role of the cytokine interleukin (IL)-6 and its utility
      as a biomarker or therapeutic target have been the source of much debate,
      presumably due to the complex pro- and anti-inflammatory effects of this
      cytokine. We previously developed a nonlinear ordinary differential equation
      (ODE) model to explain the dynamics of endotoxin (lipopolysaccharide; LPS)
      induced acute inflammation and associated whole-animal damage/dysfunction (a
      proxy for the health of the organism), along with the inflammatory mediators
      tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and nitric oxide (NO). The model
      was partially calibrated using data from endotoxemic C57Bl/6 mice. Herein, we
      investigated the sensitivity of the area under the damage curve (AUCD) to the 51
      rate parameters of the ODE model for different levels of simulated LPS challenges
      using a global sensitivity approach called Random Sampling High Dimensional Model
      Representation (RS-HDMR). We explored sufficient parametric Monte Carlo samples
      to generate the variance-based Sobol' global sensitivity indices, and found that
      inflammatory damage was highly sensitive to the parameters affecting the activity
      of IL-6 during the different stages of acute inflammation. The AUCIL6 showed a
      bimodal distribution, with the lower peak representing healthy response and the
      higher peak representing sustained inflammation. Damage was minimal at low
      AUCIL6, giving rise to a healthy response. In contrast, intermediate levels of
      AUCIL6 resulted in high damage, and this was due to the insufficiency of damage
      recovery driven by anti-inflammatory responses from IL-10 and the activation of
      positive feedback sustained by IL-6. At high AUCIL6, damage recovery was
      interestingly restored in some population of simulated animals due to the NO
      mediated anti-inflammatory responses. These observations suggest that the host's
      health status during acute inflammation depends in a nonlinear fashion on the
      magnitude of the inflammatory stimulus, on the host's propensity to produce IL-6,
      and on NO-mediated downstream responses.

PMID- 24909495
TI  - Cancer cell metabolism and developmental homeodomain/POU domain transcription
      factors: a connecting link.
AB  - The human race is afflicted with more than 100 types of cancer with diversified
      underlying genetic events. Still, altered metabolism (known as 'Warburg effect')
      and unrestrained cellular proliferation are precise traits of all cancers, being
      governed by the expression of genes. The obligatory energy for the proliferating
      neoplastic cells is endowed through the glycolytic pathway, albeit, lesser ATP is
      generated in this metabolic process. So, some perceptible cancer cell specific
      signalling is at the base of the transformed metabolism. Concurrently, the
      regulators of gene expression, transcription factors, have been observed to be
      one of the driving forces for tumourigenesis through transcriptional activation
      of genes involved not only in proliferation, growth and survival signalling, but
      also in glycolysis. This may be exemplified by the extensively studied metabolic
      functions of the transcriptional regulator, hypoxia inducible factor 1 (HIF1),
      which transactivates genes of the major enzymes of glycolysis. Preliminary
      investigation of a vital group of transcription factors, homeodomain
      transcription factors, revealed association with the process of development of an
      organism. The homeodomain transcription factors are, however, also found to be
      involved in the tumourigenesis process, with little or no information on their
      involvement in cancer cell metabolism. So, this is a review of the existing
      knowledge on homeodomain transcription factor/s for deciphering their involvement
      in neoplastic metabolism and it emerges that homeodomain transcription factors
      influence the transformed metabolic pathway in a circuitous manner. 

PMID- 24909496
TI  - Novel surgical technique to prevent pancreatic fistula in distal pancreatectomy
      using a patch of the falciform ligament.
AB  - PURPOSE: Pancreatic fistula (PF) is a serious complication of pancreatectomy and
      many techniques and devices have been designed to prevent PF and abdominal
      bleeding after pancreatectomy. We report a modified technique using a patch of
      the falciform ligament to prevent PF formation after distal pancreatectomy (DP).
      METHOD: On completion of DP, the main pancreatic duct is sutured. The remnant
      pancreas is then closely patched and sutured vertically to the falciform ligament
      using 3-0 polypropylene suture. We compared the results of this method (group 1)
      with those of the simple method of covering the remnant pancreas with the
      falciform ligament (group 2). RESULTS: We performed this method in 14 patients
      undergoing DP. The rate of grade B or C PF in group 1 (7.1 %) was lower than that
      in group 2 (46 %). CONCLUSION: This is a simple and effective method of
      preventing PF fistula in DP.

PMID- 24909497
TI  - Robotic Nissen fundoplication for gastroesophageal reflux disease: a meta
      analysis of prospective randomized controlled trials.
AB  - PURPOSE: Since its introduction, the Da Vinci surgical system for the treatment
      of gastroesophageal reflux disease (GERD) has been the subject of much
      controversy. Several prospective randomized controlled trials, conducted to
      assess its effectiveness and safety, have revealed differences. We performed this
      meta-analysis to evaluate the efficiency and safety of robotic Nissen
      fundoplication for GERD. METHODS: We performed a comprehensive search of PubMed,
      Embase, and OVID-MEDLINE, from 1950 to the present, with daily updates generated
      by a computer, to identify all published papers on robotic Nissen fundoplication
      for the treatment of GERD. The meta-analysis was performed by Review Manager
      Version 5.0. Differences of the overall effect were considered significant at P <
      0.05 with a 95 % confidence interval (95 % CI). RESULTS: Five studies with a
      collective total of 160 patients were included. Apart from intra-operative and
      post-operative complications, which were excluded because of incomplete primary
      data, there were no significant differences in outcomes, including of total
      operation interval (P = 0.16), effective operation interval (P = 0.95), post
      operative dysphagia (P = 0.94), intra-operative conversion (P = 0.94), re
      operation (P = 0.43), hospital stay (P = 0.97) and in-hospital costs (P = 0.08).
      CONCLUSIONS: As current data do not clarify the advantages of the Da Vinci
      surgical system in Nissen fundoplication for GERD, we believe that a large a
      multi-center controlled trial is warranted.

PMID- 24909498
TI  - Mortality occurrence and pathogen detection in Crassostrea gigas and Mytilus
      galloprovincialis close-growing in shallow waters (Goro lagoon, Italy).
AB  - The complex interactions occurring between farmed bivalves and their potential
      pathogens in the circumstances of global climate changes are current matter of
      study, owing to the recurrent production breakdowns reported in Europe and other
      regions of the world. In the frame of Project FP7-KBBE-2010-4 BIVALIFE, we
      investigated the occurrence of mortality and potential pathogens during the
      Spring-Summer transition in Crassostrea gigas and Mytilus galloprovincialis
      cohabiting in the shallow waters of one northern Italian lagoon (Sacca di Goro,
      Adriatic Sea) and regarded as susceptible and resistant species, respectively. In
      2011, limited bivalve mortality was detected in the open-field trial performed
      with 6-12 month old spat whereas subsequent trials with 2-3 month old spat
      produced almost complete (2012) and considerable (2013) oyster mortality.
      Macroscopical examination and histology excluded the presence of notifiable
      pathogens but, in the sampling preceding the massive oyster spat mortality of
      2012, a MUdeleted variant of OsHV-1 DNA was found in wide-ranging amounts in all
      analyzed oysters in conjunction with substantial levels of Vibrio splendidus and
      Vibrio aestuarianus. The large oyster spat mortality with borderline OsHV-1
      positivity recorded in 2013 supports the multi-factorial etiology of the
      syndrome. This is the first report of a OsHV-1 (under a form interpreted as the
      variant MUVar) in the Goro lagoon. Transcriptional host footprints are under
      investigation to better understand the bivalve response to environmental factors,
      included viral and bacterial pathogens, in relation to the observed mortalities. 

PMID- 24909500
TI  - New antibiotics for skin and skin-structure infections.

PMID- 24909499
TI  - Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and
      skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non
      inferiority trial.
AB  - BACKGROUND: New antibiotics are needed to treat infections caused by drug
      resistant bacteria. Tedizolid is a novel oxazolidinone antibacterial drug
      designed to provide enhanced activity against Gram-positive pathogens. We aimed
      to assess the efficacy and safety of intravenous to oral tedizolid for treatment
      of patients with acute bacterial skin and skin-structure infections. METHODS:
      ESTABLISH-2 was a randomised, double-blind, phase 3, non-inferiority trial done
      between Sept 28, 2011, and Jan 10, 2013, at 58 centres in nine countries.
      Patients (aged >=12 years) with acute bacterial skin and skin-structure
      infections (cellulitis or erysipelas, major cutaneous abscess, or wound
      infection) that had a minimum lesion area of 75 cm(2) and were suspected or
      documented to be associated with a Gram-positive pathogen, were randomly assigned
      (1:1), via an interactive voice-response system with block randomisation, to
      receive intravenous once-daily tedizolid (200 mg for 6 days) or twice-daily
      linezolid (600 mg for 10 days), with optional oral step-down. Randomisation was
      stratified by geographic region and type of acute bacterial skin and skin
      structure infection. The primary endpoint was early clinical response (>=20%
      reduction in lesion area at 48-72 h compared with baseline), with a non
      inferiority margin of -10%. Analysis was by intention to treat. This study is
      registered with ClinicalTrials.gov, number NCT01421511. FINDINGS: 666 patients
      were randomly assigned to receive tedizolid (n=332) or linezolid (n=334). 283
      (85%) patients in the tedizolid group and 276 (83%) in the linezolid group
      achieved early clinical response (difference 2.6%, 95% CI -3.0 to 8.2), meeting
      the prespecified non-inferiority margin. Gastrointestinal adverse events were
      less frequent with tedizolid than linezolid, taking place in 52 (16%) of 331
      patients and 67 (20%) of 327 patients in the safety population. Treatment
      emergent adverse events leading to discontinuation of study drug were reported by
      one (<1%) patient in the tedizolid group and four (1%) patients in the linezolid
      group. INTERPRETATION: Intravenous to oral once-daily tedizolid 200 mg for 6 days
      was non-inferior to twice-daily linezolid 600 mg for 10 days for treatment of
      patients with acute bacterial skin and skin-structure infections. Tedizolid could
      become a useful option for the treatment of acute bacterial skin and skin
      structure infections in the hospital and outpatient settings. FUNDING: Cubist
      Pharmaceuticals.

PMID- 24909501
TI  - Racial disparities and colorectal cancer survival in older adults with and
      without diabetes mellitus.
AB  - BACKGROUND AND AIM: To investigate whether pre-existing diabetes modifies racial
      disparities in colorectal cancer (CRC) survival. METHODS: We analyzed prospective
      data from 16 977 patients (age >= 67 years) with CRC from the Surveillance
      Epidemiology and End Results (SEER)-Medicare database. SEER registries included
      data on demographics, tumor characteristics, and treatment. Medicare claims were
      used to define pre-existing diabetes and comorbid conditions. Mortality was
      confirmed in both sources. RESULTS: At baseline, 1332 (8%) were African Americans
      and 26% had diabetes (39% in blacks; 25% in whites). From 2000 to 2005, more than
      half of the participants died (n = 8782, 52%). This included 820 (62%) deaths
      (23.8 per 100 person-years) among blacks, and 7962 (51%) deaths (16.6 per 100
      person-years) among whites. Among older adults with diabetes, blacks had
      significantly higher risk of all-cause and CRC mortality after adjustments for
      demographic characteristics (hazard ratio [HR], 95% confidence interval [CI]:
      1.21 [1.08-1.37] and 1.21 [1.03-1.42]), respectively, but these associations
      attenuated to null after additional adjustments for cancer stage and grade. Among
      adults without diabetes, the risk of all-cause mortality (HR [95% CI]: 1.14 [1.04
      1.25]) and CRC mortality (HR [95% CI]: 1.21 [1.08-1.36]) remained higher in
      blacks than whites in fully adjusted models that included demographic variables,
      cancer stage, grade, treatments, and comorbidities. CONCLUSIONS: Among older
      adults with CRC, diabetes is an effect modifier on the relationship between race
      and mortality. Racial disparities in survival were explained by demographics,
      cancer stage, and grade in patients with diabetes.

PMID- 24909502
TI  - Neuroplasticity of central corticotropin-releasing factor and serotonergic
      systems in anxiety-related behavior.

PMID- 24909503
TI  - Physiologic variations in venous and arterial hemodynamics in response to
      postural changes at the thoracic outlet in normal volunteers.
AB  - BACKGROUND: Hemodynamic changes in vascular flow and waveforms measured across
      the thoracic outlet (TO) during positional changes may occur in normal
      individuals. The aim of this study was to establish the prevalence of significant
      arterial and venous hemodynamic variation in the limbs of normal volunteers
      during standardized upper extremity positional changes. METHODS: Using Doppler
      ultrasound and photoplethysmography (PPG), we evaluated arterial and venous flow
      in 100 limbs of 50 normal volunteers in neutral position and in 5 different
      standardized arm positions, including 90 degrees  arm abduction (with head in
      neutral position, head turned ipsilaterally, and head turned contralaterally),
      arm extended above the head at 180 degrees , and arm hyperextended at 200 degrees
      . RESULTS: There was great variability in the prevalence of abnormal venous and
      arterial flow changes depending on the arm position. Venous flow anomalies (loss
      of flow phasicity resulting in continuous, minimally continuous, or absent flow)
      were demonstrated in 60% of the limbs. The maneuver producing the greatest
      prevalence of venous flow abnormality was 90 degrees  arm abduction with
      contralateral head turn (34% of limbs), while arm hyperextension produced the
      least venous flow abnormalities (25% of limbs). In 13% of the limbs arterial flow
      abnormalities were found by PPG (absent tracings in 10% and dampened waveform in
      5%), while 23% of the limbs showed increased arterial velocities (positional to
      neutral velocity ratio >2.0). The arm position producing the greatest prevalence
      of arterial flow anomaly was hyperextension (21% of limbs); while the arm
      positioning at 90 degrees  of abduction with the head in neutral position
      resulted in no arterial flow abnormalities. CONCLUSIONS: The prevalence of upper
      extremity venous and arterial hemodynamic changes varies substantially in
      different arm positions. Our data suggest that physiologic anomalies in venous
      flow across the TO during postural changes are very common, while the absence of
      finger PPG arterial tracings occur in a very small percentage of the population.
      Abnormal venous flow across the TO with postural changes should be considered a
      highly prevalent finding in the normal population, and therefore carries little
      value in the diagnosis of TO syndrome. On the other hand, absence of arterial
      waveforms measured at the fingers by PPG testing during positional changes occurs
      in a small percentage of the normal population, and may represent abnormal
      compression at the TO in patients with upper extremity symptomatology.

PMID- 24909504
TI  - TP53 status predicts long-term survival in locally advanced breast cancer after
      primary chemotherapy.
AB  - BACKGROUND: Before the advent of neoadjuvant chemotherapy, radiotherapy and
      surgery alone were associated with a high risk of uncontrolled locoregional
      relapses in locally advanced breast cancer (LABC). MATERIAL AND METHODS: In the
      1990s we initiated two neoadjuvant protocols, where patients with LABC were given
      either doxorubicin qW or 5-fluorouracil/mitomycin (FUMI) q3W to shrink the
      tumours prior to mastectomy and postoperative radiotherapy. Previously, we
      reported TP53 mutation status to predict a poor response to chemotherapy. Here,
      we present the long-term survival data, with a follow-up of 20 years in the
      doxorubicin (n = 90) and 15 years in the FUMI trial (n = 34). RESULTS: Patients
      in the doxorubicin trial with TP53-mutated tumours experienced a shorter
      recurrence-free (RFS; 14 vs. 83 months, p < 0.001) and overall survival (OS; 35
      vs. 90 months, p < 0.001) than patients with TP53 wt tumours. Similarily, TP53
      mutations were associated with a shorter OS (22 vs. 80 months, p = 0.03) and a
      tendency to shorter RFS (17 vs. 33 months, p = 0.06) in patients treated with
      FUMI. Furthermore, axillary lymph node metastases predicted shorter OS, but only
      in patients treated with doxorubicin (49 vs. 142 months, p < 0.04). Applying
      multivariate analysis, TP53 mutations predicted inferior RFS (p < 0.001) as well
      as OS (p < 0.001), independently of axillary lymph node status. Isolated local
      recurrences, without simultaneous distant metastases, occurred in seven patients
      only in the two trials. Interestingly, chest wall radiation fibrosis predicted
      improved OS (p = 0.004). CONCLUSION: TP53 inactivating mutations are associated
      with an inferior long-term prognosis in patients with LABC treated with
      conventional chemotherapy.

PMID- 24909505
TI  - Achieving consistent image quality and overall radiation dose reduction for
      coronary CT angiography with body mass index-dependent tube voltage and tube
      current selection.
AB  - AIM: To develop a quantitative body mass index (BMI)-dependent tube voltage and
      tube current selection method for obtaining consistent image quality and overall
      dose reduction in computed tomography coronary angiography (CTCA). METHODS AND
      MATERIALS: The images of 190 consecutive patients (group A) who underwent CTCA
      with fixed protocols (100 kV/193 mAs for 100 patients with a BMI of <27 and 120
      kV/175 mAs for 90 patients with a BMI of >27) were retrospectively analysed and
      reconstructed with an adaptive statistical iterative reconstruction (ASIR)
      algorithm at 50% blending. Image noise was measured and the relationship to BMI
      was studied to establish BMI-dependent tube current for obtaining CTCA images
      with user-specified image noise. One hundred additional cardiac patients (group
      B) were examined using prospective triggering with the BMI-dependent tube
      voltage/current. CTCA image-quality score, image noise, and effective dose from
      groups B and C (subgroup of A of 100 patients examined with prospective
      triggering only) were obtained and compared. RESULTS: There was a linear
      relationship between image noise and BMI in group A. Using a BMI-dependent tube
      current in group B, an average CTCA image noise of 27.7 HU (target 28 HU) and
      31.7 HU (target 33 HU) was obtained for the subgroups of patients with BMIs of
      >27 and of <27, respectively, and was independent of patient BMI. There was no
      difference between image-quality scores between groups B and C (4.52 versus 4.60,
      p > 0.05). The average effective dose for group B (2.56 mSv) was 42% lower than
      group C (4.38 mSv; p < 0.01). CONCLUSION: BMI-dependent tube voltage/current
      selection in CTCA provides an individualized protocol that generates consistent
      image quality and helps to reduce overall patient radiation dose.

PMID- 24909506
TI  - Comparison of diffusion-weighted imaging between high and standard b-values for
      primary central nervous system lymphoma.
AB  - AIM: To investigate the utility of diffusion-weighted (DW) magnetic resonance
      imaging (MRI) with a high b-value (b = 3000 s/mm(2)) compared with standard b
      value (b = 1000 s/mm(2)) DW imaging in patients with primary central nervous
      system lymphoma (PCNSL). MATERIALS AND METHODS: High and standard b-value (b =
      3000 and 1000 s/mm(2), respectively) DW images were acquired in 15 patients with
      PCNSL. The number and location of the lesions were assessed. MRI signal
      intensities (SIs), signal-to-noise ratios (SNRs), contrast-to-noise ratios
      (CNRs), contrast ratios (CRs), and apparent diffusion coefficients (ADCs) of the
      lesions and normal parenchyma were measured. RESULTS: Thirty-two lesions in 15
      patients were revealed. Twenty-seven of the lesions were hyperintense at DW MRI
      with high and standard b-values; high b-value images revealed five additional
      lesions. Lesions were also more conspicuous at high b-value (b = 3000 s/mm(2)) DW
      MRI compared to standard b-value images (b = 1000 s/mm(2)). SNR, CNR, and ADC
      values in lesions and normal parenchyma were lower in the b = 3000 s/mm(2) images
      compared to the b = 1000 s/mm(2) images (SNR: 250.7 +/- 124.7 versus 112.3 +/-
      68.7; CNR: 83.4 +/- 74.7 versus 59.6 +/- 60.4, b = 1000 and 3000 s/mm(2),
      respectively). The CR was significantly greater in the b = 3000 s/mm(2) images
      compared to the b = 1000 s/mm(2) images (CR: 0.28 +/- 0.13 versus 0.18 +/- 0.10).
      CONCLUSIONS: Although quantitative analyses revealed higher SI, SNR, and CNR
      values in standard b-value (b = 1000 s/mm(2)) DW images, higher b-value imaging
      could be beneficial for detecting additional lesions and improving the contrast
      between lesions and normal tissue in patients with PCNSL.

PMID- 24909507
TI  - Neonatal thymectomy favors Helicobacter pylori-promoted gastric mucosa-associated
      lymphoid tissue lymphoma lesions in BALB/c mice.
AB  - Neonatal thymectomy in BALB/c mice has been described as a model of gastric
      mucosa-associated lymphoid tissue (MALT) lymphoma (GML). By using this
      experimental system, we screened, for the first time to our knowledge,
      Helicobacter pylori GML-associated strains for their capacity to promote disease.
      A cohort of BALB/c mice underwent thymectomy at day 3 after birth (d3Tx).
      Successful thymic ablation was evaluated by the degree of lymphopenia in blood
      samples collected at 4 weeks of age. d3Tx and non-thymectomized controls were
      infected with either GML strains (B38 or B47) or control strains (SS1 or TN2GF4).
      Gastric samples collected at 6, 12, and 18 months after infection were studied
      for bacteria content, and submitted to histological, immunochemical, molecular,
      and immunological analyses. Severe gastric inflammation was only observed in d3Tx
      mice. In these animals, the gastric lamina propria was infiltrated with lymphoid
      cells organized in follicles composed of B cells with few infiltrating T cells.
      PCR of D/J IgH gene segments proved the monoclonality of infiltrating B cells,
      which strongly correlated with the presence of lymphoepithelial lesions. B-cell
      infiltrates were particularly prominent in mice infected with the B47-GML strain.
      No pathological changes were detected in noninfected d3Tx mice. We identified new
      H. pylori isolates adapted to the mouse stomach with high potential of GML
      development, which is only revealed in hosts rendered lymphopenic by neonatal
      thymic ablation. 

PMID- 24909508
TI  - Age-dependent changes cooperatively impact skeletal muscle regeneration after
      compartment syndrome injury.
AB  - Declining skeletal muscle function, due to injury and aging (sarcopenia), results
      in a significantly decreased quality of life and is a major cause of disability
      in the United States. Studies examining recovery from muscle injury in models of
      older animals principally used insults that primarily affect only the myofibers
      without affecting the muscle tissue microenvironment. This type of injury does
      not adequately represent the full extent of tissue damage observed in older
      humans, which encompasses injury not only to the muscle fibers, but also to the
      surrounding tissue components, such as the vasculature and nerves. Previously, we
      described a novel rat model of compression-induced muscle injury that results in
      multicomponent injury to the muscle and adequately mimics compartment syndrome
      injuries seen in patients. Herein, we characterized tissue regeneration in young,
      adult, and aged rats after compartment syndrome injury. We observed significant
      differences between the regeneration process in the different aged rats that
      involved muscle function, tissue anatomical features, neovascularization, and
      innervation. Compared to young rats, adult rats had delayed functional recovery,
      whereas the aged rats were deficient in their regenerative capacity. Age
      dependent changes in both the ability to restore the contractile apparatus and
      myogenesis are important, and must be taken into consideration when designing
      therapies for the treatment of muscle injury. 

PMID- 24909509
TI  - Prognostic and predictive value of metabolic tumor volume on (18)F-FDG PET/CT in
      advanced biliary tract cancer treated with gemcitabine/oxaliplatin with or
      without erlotinib.
AB  - This study aimed to evaluate the prognostic significance and predictive
      performance of volume-based parameter of (18)F-fluorodeoxyglucose ((18)F-FDG)
      positron emission tomography/computed tomography (PET/CT) in biliary tract cancer
      (BTC). Of the 268 patients who were enrolled onto phase III
      gemcitabine/oxaliplatin (GEMOX) versus GEMOX/erlotinib trial, a total of 48
      patients had pretreatment (18)F-FDG PET/CT available for analysis. Maximum
      standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total
      lesion glycolysis for the primary tumor were measured. The prognostic
      significance of these parameters and clinicopathological variables was assessed
      by Cox proportional hazards regression analysis. A cutoff of 98.8 ml for the
      MTVliver was the best discriminative value for predicting overall survival (>9
      months). Multivariate analyses with adjustments for age, performance status, and
      disease status showed that only MTVliver was an independent prognostic factor
      associated with overall survival (HR 2.149, 95 % CI 1.124-4.109, P = 0.021).
      SUVmax did not show any correlation with overall survival. For patients in the
      high-MTVMBP group, overall survival was longer in the chemotherapy plus erlotinib
      group than in the chemotherapy-alone group [median 8.3 months (5.5-11.1) vs. 4.0
      months (0.0-8.0); P = 0.048]. MTV may be considered as a significant independent
      metabolic prognostic factor for overall survival in patients with BTC and
      predictive marker for the selection of patients for the addition of erlotinib to
      first-line chemotherapy.

PMID- 24909510
TI  - Quasi-specific access of the potassium channel inactivation gate.
AB  - Many voltage-gated potassium channels open in response to membrane depolarization
      and then inactivate within milliseconds. Neurons use these channels to tune their
      excitability. In Shaker K(+) channels, inactivation is caused by the cytoplasmic
      amino terminus, termed the inactivation gate. Despite having four such gates,
      inactivation is caused by the movement of a single gate into a position that
      occludes ion permeation. The pathway that this single inactivation gate takes
      into its inactivating position remains unknown. Here we show that a single gate
      threads through the intracellular entryway of its own subunit, but the tip of the
      gate has sufficient freedom to interact with all four subunits deep in the pore,
      and does so with equal probability. This pathway demonstrates that flexibility
      afforded by the inactivation peptide segment at the tip of the N-terminus is used
      to mediate function. 

PMID- 24909512
TI  - Brucine suppresses ethanol intake and preference in alcohol-preferring Fawn
      Hooded rats.
AB  - AIM: Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine
      receptor antagonist. We hypothesize that BRU may modify alcohol consumption by
      acting at glycine receptors, and evaluated the pharmacodynamic profiles and
      adverse effects of BRU in rat models of alcohol abuse. METHODS: Alcohol
      preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg,
      sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle
      choice drinking paradigm, ethanol/sucrose operant self-administration paradigm
      and 5-d ethanol deprivation test. In addition, open field test was used to assess
      the general locomotor activity of FH/Wjd rats, and conditioned place preference
      (CPP) was conducted to assess conditioned reinforcing effect. RESULTS: In ethanol
      2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days
      dose-dependently decreased the ethanol intake associated with a compensatory
      increase of water intake, but unchanged the daily total fluid intake and body
      weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg)
      administered before each testing session significantly decreased the number of
      lever presses for ethanol and the ethanol intake, without affecting the number of
      sucrose (10%) responses, total sucrose intake, and the number of lever presses
      for water. Acute treatment with BRU (30 mg/kg) completely suppressed the
      deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20,
      and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place
      preference or aversion. CONCLUSION: BRU selectively decreases ethanol consumption
      with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy
      for alcoholism.

PMID- 24909513
TI  - Metergoline inhibits the neuronal Nav1.2 voltage-dependent Na(+) channels
      expressed in Xenopus oocytes.
AB  - AIM: Metergoline is an ergot-derived psychoactive drug that acts as a ligand for
      serotonin and dopamine receptors. The aim of this study was to investigate the
      regulatory effects of metergoline on the neuronal Nav1.2 voltage-dependent Na(+)
      channels in vitro. METHODS: Xenopus oocytes were injected with cRNAs encoding rat
      brain Nav1.2 alpha and beta1 subunits. Voltage-activated Na(+) currents were
      recorded using two-electrode voltage clamp technique. Drugs were applied though
      perfusion. RESULTS: Both metergoline and lidocaine reversibly and concentration
      dependently inhibited the peak of Na(+) currents with IC50 values of 3.6 +/- 4.2
      and 916.9 +/- 98.8 MUmol/L, respectively. Metergoline (3 MUmol/L) caused a 6.8 +/
      1.2 mV depolarizing shift of the steady-state activation curve of the Na(+)
      currents, and did not alter the inactivation curve. In contrast, lidocaine (3
      MUmol/L) caused a 12.7 +/- 1.2 mV hyperpolarizing shift of the inactivation curve
      of the Na(+) currents without changing the steady-state activation curve. Both
      metergoline and lidocaine produced tonic and use-dependent inhibition on the peak
      of Na(+) currents. CONCLUSION: Metergoline exerts potent inhibition on the
      activity of neuronal Nav1.2 channels, which may contribute to its actions on the
      central nervous system.

PMID- 24909514
TI  - RIP3 overexpression sensitizes human breast cancer cells to parthenolide in vitro
      via intracellular ROS accumulation.
AB  - AIM: Receptor-interacting protein 3 (RIP3) is involved in tumor necrosis factor
      receptor signaling, and results in NF-kappaB-mediated prosurvival signaling and
      programmed cell death. The aim of this study was to determine whether
      overexpression of the RIP3 gene could sensitize human breast cancer cells to
      parthenolide in vitro. METHODS: The expression of RIP3 mRNA in human breast
      cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435 and T47D) was detected using RT
      PCR. Both MDA-MB-231 and MCF-7 cells were transfected with RIP3 expression or
      blank vectors via lentivirus. Cell viability was measured with MTT assay;
      intracellular ROS level and cell apoptosis were analyzed using flow cytometry.
      RESULTS: RIP3 mRNA expression was not detected in the four human breast cancer
      cell lines tested. However, the transfection induced higher levels of RIP3
      protein in MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of RIP3
      decreased the IC50 values of parthenolide from 17.6 to 12.6 MUmol/L in MCF-7
      cells, and from 16.6 to 9.9 MUmol/L in MDA-MB-231 cells. Moreover, overexpression
      of RIP3 significantly increased parthenolide-induced apoptosis and ROS
      accumulation in MCF-7 and MDA-MB-231 cells. Pretreatment with N-acetyl-cysteine
      abrogated the increased sensitivity of RIP3-transfected MCF-7 and MDA-MB-231
      cells to parthenolide. CONCLUSION: Overexpression of RIP3 sensitizes MCF-7 and
      MDA-MB-231 breast cancer cells to parthenolide in vitro via intracellular ROS
      accumulation.

PMID- 24909515
TI  - Dopamine D1 receptor activation induces dehydroepiandrosterone sulfotransferase
      (SULT2A1) in HepG2 cells.
AB  - AIM: Dopamine receptors are present in the nervous system and also widely
      distributed in the periphery. The aim of this study was to investigate the role
      of D1 subtype dopamine receptors (DRD1) in the regulation of
      dehydroepiandrosterone sulfotransferase (SULT2A1) in HepG2 cells. METHODS: HepG2
      cells were treated with DRD1 agonists with or without DRD1 antagonist for 9 d.
      DRD1 and SULT2A1 mRNA expression, protein expression, and SULT2A1 activity were
      detected using RT-PCR, Western blotting and HPLC, respectively. The level of cAMP
      was measured using a commercial kit. RESULTS: All the 5 DR subtypes (DRD1-DRD5)
      were found to be expressed in HepG2 cells. Treatment of HepG2 cells with the
      specific DRD1 agonists SKF82958 (2.5 MUmol/L) or SKF38393 (5 and 50 MUmol/L)
      significantly increased the mRNA and protein expression of both DRD1 and SULT2A1,
      and increased SULT2A1 activity and cAMP levels. These effects were partially
      blocked by co-treatment with the specific DRD1 antagonist SCH23390 (2.5 MUmol/L).
      In addition, transfection of HepG2 cells with DRD1-specific siRNAs decreased DRD1
      mRNA expression by 40%, which resulted in the reduction of SULT2A1 mRNA
      expression by 60%, protein expression by 40%, and enzyme activity by 20%.
      CONCLUSION: DRD1 activation upregulates DRD1 and SULT2A1 expression and SULT2A1
      activity in HepG2 cells, suggesting that the DRD1 subtype may be involved in the
      metabolism of drugs and xenobiotics through regulating SULT2A1.

PMID- 24909517
TI  - Predicting autism diagnosis by 7 years of age using parent report of infant
      social communication skills.
AB  - AIM: The aim of this study is to identify social communication skills in infancy
      which predict autism spectrum disorder (ASD) diagnosis by 7 years as compared
      with children with other developmental difficulties or typical development from
      within a population sample. METHODS: Children with an ASD (n = 41), developmental
      delay (n = 28), language impairment (n = 47) and typical development (n = 41)
      were drawn from a large, longitudinal community sample following children from 8
      months to 7 years of age, the Early Language in Victoria Study. At 7 years of
      age, early social communication skills at 8, 12 and 24 months from the
      Communication and Symbolic Behavior Scales Infant-Toddler Checklist and the
      MacArthur-Bates Communicative Development Inventory: Words and Gestures were
      compared between groups and used to predict ASD diagnosis. RESULTS: Significant
      predictors of ASD diagnosis were found from 8 months, predominantly focused on
      gesture use and communicative behaviours, such as requesting and joint attention.
      While comparisons between children with ASD and children with language impairment
      and typical development revealed differences from 8 months of age, the
      developmental delay group did not differ significantly from ASD on any measure
      until 24 months of age. At 24 months, children with ASD had lower Communication
      and Symbolic Behavior Scales Use of Communication scores as compared with all
      other groups. CONCLUSIONS: The capacity to identify early markers of ASD should
      facilitate awareness of the risk of an ASD as compared with other developmental
      problems and point to the need for further developmental assessment, monitoring
      and provision of early intervention if indicated.

PMID- 24909516
TI  - Tubulin inhibitors: pharmacophore modeling, virtual screening and molecular
      docking.
AB  - AIM: To construct a quantitative pharmacophore model of tubulin inhibitors and to
      discovery new leads with potent antitumor activities. METHODS: Ligand-based
      pharmacophore modeling was used to identify the chemical features responsible for
      inhibiting tubulin polymerization. A set of 26 training compounds was used to
      generate hypothetical pharmacophores using the HypoGen algorithm. The structures
      were further validated using the test set, Fischer randomization method, leave
      one-out method and a decoy set, and the best model was chosen to screen the Specs
      database. Hit compounds were subjected to molecular docking study using a
      Molecular Operating Environment (MOE) software and to biological evaluation in
      vitro. RESULTS: Hypo1 was demonstrated to be the best pharmacophore model that
      exhibited the highest correlation coefficient (0.9582), largest cost difference
      (70.905) and lowest RMSD value (0.6977). Hypo1 consisted of one hydrogen-bond
      acceptor, a hydrogen-bond donor, a hydrophobic feature, a ring aromatic feature
      and three excluded volumes. Hypo1 was validated with four different methods and
      had a goodness-of-hit score of 0.81. When Hypo1 was used in virtual screening of
      the Specs database, 952 drug-like compounds were revealed. After docking into the
      colchicine-binding site of tubulin, 5 drug-like compounds with the required
      interaction with the critical amino acid residues and the binding free energies <
      -4 kcal/mol were selected as representative leads. Compounds 1 and 3 exhibited
      inhibitory activity against MCF-7 human breast cancer cells in vitro. CONCLUSION:
      Hypo1 is a quantitative pharmacophore model for tubulin inhibitors, which not
      only provides a better understanding of their interaction with tubulin, but also
      assists in discovering new potential leads with antitumor activities.

PMID- 24909511
TI  - Androgen receptor: structure, role in prostate cancer and drug discovery.
AB  - Androgens and androgen receptors (AR) play a pivotal role in expression of the
      male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS)
      and prostate cancer, are associated with alterations in AR functions. Indeed,
      androgen blockade by drugs that prevent the production of androgens and/or block
      the action of the AR inhibits prostate cancer growth. However, resistance to
      these drugs often occurs after 2-3 years as the patients develop castration
      resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key
      regulator. Early studies focused on the functional domains of the AR and its
      crucial role in the pathology. The elucidation of the structures of the AR DNA
      binding domain (DBD) and ligand binding domain (LBD) provides a new framework for
      understanding the functions of this receptor and leads to the development of
      rational drug design for the treatment of prostate cancer. An overview of
      androgen receptor structure and activity, its actions in prostate cancer, and how
      structural information and high-throughput screening have been or can be used for
      drug discovery are provided herein. 

PMID- 24909518
TI  - MiningABs: mining associated biomarkers across multi-connected gene expression
      datasets.
AB  - BACKGROUND: Human disease often arises as a consequence of alterations in a set
      of associated genes rather than alterations to a set of unassociated individual
      genes. Most previous microarray-based meta-analyses identified disease-associated
      genes or biomarkers independent of genetic interactions. Therefore, in this
      study, we present the first meta-analysis method capable of taking gene
      combination effects into account to efficiently identify associated biomarkers
      (ABs) across different microarray platforms. RESULTS: We propose a new meta
      analysis approach called MiningABs to mine ABs across different array-based
      datasets. The similarity between paired probe sequences is quantified as a bridge
      to connect these datasets together. The ABs can be subsequently identified from
      an "improved" common logit model (c-LM) by combining several sibling-like LMs in
      a heuristic genetic algorithm selection process. Our approach is evaluated with
      two sets of gene expression datasets: i) 4 esophageal squamous cell carcinoma and
      ii) 3 hepatocellular carcinoma datasets. Based on an unbiased reciprocal test, we
      demonstrate that each gene in a group of ABs is required to maintain high cancer
      sample classification accuracy, and we observe that ABs are not limited to genes
      common to all platforms. Investigating the ABs using Gene Ontology (GO)
      enrichment, literature survey, and network analyses indicated that our ABs are
      not only strongly related to cancer development but also highly connected in a
      diverse network of biological interactions. CONCLUSIONS: The proposed meta
      analysis method called MiningABs is able to efficiently identify ABs from
      different independently performed array-based datasets, and we show its validity
      in cancer biology via GO enrichment, literature survey and network analyses. We
      postulate that the ABs may facilitate novel target and drug discovery, leading to
      improved clinical treatment. Java source code, tutorial, example and related
      materials are available at "http://sourceforge.net/projects/miningabs/".

PMID- 24909519
TI  - Swarm intelligence inspired shills and the evolution of cooperation.
AB  - Many hostile scenarios exist in real-life situations, where cooperation is
      disfavored and the collective behavior needs intervention for system efficiency
      improvement. Towards this end, the framework of soft control provides a powerful
      tool by introducing controllable agents called shills, who are allowed to follow
      well-designed updating rules for varying missions. Inspired by swarm intelligence
      emerging from flocks of birds, we explore here the dependence of the evolution of
      cooperation on soft control by an evolutionary iterated prisoner's dilemma (IPD)
      game staged on square lattices, where the shills adopt a particle swarm
      optimization (PSO) mechanism for strategy updating. We demonstrate that not only
      can cooperation be promoted by shills effectively seeking for potentially better
      strategies and spreading them to others, but also the frequency of cooperation
      could be arbitrarily controlled by choosing appropriate parameter settings.
      Moreover, we show that adding more shills does not contribute to further
      cooperation promotion, while assigning higher weights to the collective knowledge
      for strategy updating proves a efficient way to induce cooperative behavior. Our
      research provides insights into cooperation evolution in the presence of PSO
      inspired shills and we hope it will be inspirational for future studies focusing
      on swarm intelligence based soft control. 

PMID- 24909520
TI  - Clinicopathological features of patients with acute graft-versus-host disease of
      the upper digestive tract.
AB  - BACKGROUND AND AIMS: Acute graft-versus-host disease (GVHD) occurring within 100
      days post-transplant is one of critical factors influencing prognosis in
      transplant recipients. Among cases of GVHD of the gastrointestinal (GI) tract,
      GVHD rarely affects the upper GI. In this study, we retrospectively examined the
      frequency of upper GI GVHD and diagnostic accuracy. PATIENTS AND METHODS: From
      among 868 patients who underwent allogeneic hematopoietic stem cell
      transplantation at our hospital between January 2005 and June 2012, 115 of whom
      underwent biopsy for upper GI symptoms. The endoscopic findings and histologic
      diagnosis from these 115 patients were retrospectively analyzed. RESULTS: GVHD
      was histologically diagnosed in 85 patients overall (9.8% of all 868 transplant
      recipients). Although gastric mucosal exfoliation was not commonly observed, this
      endoscopic finding when used as a diagnostic predictor had both a specificity and
      positive predictive value (PPV) of 100%. When using redness, luster, and mucosal
      change as predictors, specificity and PPV were relatively high, suggesting that
      these gastric endoscopic findings are useful in the diagnosis of upper GI GVHD.
      Among the duodenal endoscopic findings, erosion as a diagnostic predictor had
      both a high specificity and PPV. The biopsy results often lead to a diagnosis of
      GVHD even in cases judged to be endoscopically normal. CONCLUSIONS: Among the
      gastric endoscopic findings, mucosal exfoliation, although rare, and redness,
      luster, and mucosal change are likely to be useful diagnostic predictors of upper
      GI GVHD. GVHD was frequently diagnosed in patients with endoscopically normal
      duodenum, suggesting that biopsies are important for definitive diagnosis.

PMID- 24909521
TI  - Fathers' versus mothers' social referencing signals in relation to infant anxiety
      and avoidance: a visual cliff experiment.
AB  - Infants use signals from others to guide their behavior when confronted with
      novel situations, a process called 'social referencing' (SR). Via SR, signs of
      parental anxiety can lead to infant anxiety. Little is known about differences in
      the effect of paternal and maternal SR signals on child anxiety. Using a visual
      cliff paradigm, we studied whether SR processes between fathers and their infants
      differed from mothers and their infants. Eighty-one infants aged 10-15 months
      were randomly assigned to conduct the visual cliff task with their father (n =
      41) or mother (n = 40). The infant was placed on the shallow side of the cliff
      and the parent, standing at the deep side, was instructed to encourage the infant
      to cross. Results showed that although mothers showed more intense facial
      expressions of encouragement than fathers, no differences occurred in how fast,
      and with how much anxiety, infants crossed the cliff with fathers and mothers.
      However, path analyses showed that paternal, but not maternal, expressed anxiety
      was positively associated with infant expressed anxiety and avoidance. For
      infants who participated with their mother, infants' anxious temperament was
      negatively associated with infant avoidance of the cliff. Infant anxious
      temperament moderated the link between paternal expressed anxiety and infant
      avoidance: the higher the level of infant anxious temperament the stronger the
      positive association between paternal expressed anxiety and infant's avoidance of
      the cliff. Lastly, parental encouragement was unrelated to infant expressed
      anxiety and avoidance. Our results suggest that SR processes between fathers and
      their infants differ from those between mothers and their infants. 

PMID- 24909523
TI  - Optimising debriefing for technology-enhanced simulation.

PMID- 24909524
TI  - Matters of detail: does basic science content support future learning?

PMID- 24909525
TI  - Dyad practice and the inevitability of social comparison.

PMID- 24909526
TI  - When I say ... retroactive interference.

PMID- 24909527
TI  - Debriefing for technology-enhanced simulation: a systematic review and meta
      analysis.
AB  - OBJECTIVES: Debriefing is a common feature of technology-enhanced simulation
      (TES) education. However, evidence for its effectiveness remains unclear. We
      sought to characterise how debriefing is reported in the TES literature, identify
      debriefing features that are associated with improved outcomes, and evaluate the
      effectiveness of debriefing when combined with TES. METHODS: We systematically
      searched databases, including MEDLINE, EMBASE and Scopus, and reviewed previous
      bibliographies for original comparative studies investigating the use of TES with
      debriefing in training health care providers. Reviewers, in duplicate, evaluated
      study quality and abstracted information on instructional design, debriefing and
      outcomes. Effect sizes (ES) were pooled using random-effects meta-analysis.
      RESULTS: From 10 903 potentially eligible studies, we identified 177 studies (11
      511 learners) that employed debriefing as part of TES. Key characteristics of
      debriefing (e.g. duration, educator presence and characteristics, content,
      structure/method, timing, use of video) were usually incompletely reported. A
      meta-analysis of four studies demonstrated that video-assisted debriefing has
      negligible and non-significant effects for time skills (ES = 0.10) compared with
      non-video-assisted debriefing. Meta-analysis demonstrated non-significant effects
      in favour of expert modelling with short debriefing in comparison with long
      debriefing (ES range = 0.21-0.74). Among studies comparing terminal with
      concurrent debriefing, results were variable depending on outcome measures and
      the context of training (e.g. medical resuscitation versus technical skills).
      Eight additional studies revealed insight into the roles of other debriefing
      related factors (e.g. multimedia debriefing, learner-led debriefing, debriefing
      duration, content of debriefing). Among studies that compared simulation plus
      debriefing with no intervention, pooled ESs were favourable for all outcomes (ES
      range = 0.28-2.16). CONCLUSIONS: Limited evidence suggests that video-assisted
      debriefing yields outcomes similar to those of non-video-assisted debriefing.
      Other debriefing design features show mixed or non-significant results. As
      debriefing characteristics are usually incompletely reported, future debriefing
      research should describe all the key debriefing characteristics along with their
      associated descriptors.

PMID- 24909528
TI  - Preparing medical students for future learning using basic science instruction.
AB  - OBJECTIVES: The construct of 'preparation for future learning' (PFL) is
      understood as the ability to learn new information from available resources,
      relate new learning to past experiences and demonstrate innovation and
      flexibility in problem solving. Preparation for future learning has been proposed
      as a key competence of adaptive expertise. There is a need for educators to
      ensure that opportunities are provided for students to develop PFL ability and
      that assessments accurately measure the development of this form of competence.
      The objective of this research was to compare the relative impacts of basic
      science instruction and clinically focused instruction on performance on a PFL
      assessment (PFLA). METHODS: This study employed a 'double transfer' design. Fifty
      one pre-clerkship students were randomly assigned to either basic science
      instruction or clinically focused instruction to learn four categories of
      disease. After completing an initial assessment on the learned material, all
      participants received clinically focused instruction for four novel diseases and
      completed a PFLA. The data from the initial assessment and the PFLA were
      submitted to independent-sample t-tests. RESULTS: Mean +/- standard deviation
      [SD] scores on the diagnostic cases in the initial assessment were similar for
      participants in the basic science (0.65 +/- 0.11) and clinical learning (0.62 +/-
      0.11) conditions. The difference was not significant (t[42] = 0.90, p = 0.37, d =
      0.27). Analysis of the diagnostic cases on the PFLA revealed significantly higher
      mean +/- SD scores for participants in the basic science learning condition (0.72
      +/- 0.14) compared with those in the clinical learning condition (0.63 +/- 0.15)
      (t[42] = 2.02, p = 0.05, d = 0.62). CONCLUSIONS: Our results show that the
      inclusion of basic science instruction enhanced the learning of novel related
      content. We discuss this finding within the broader context of research on basic
      science instruction, development of adaptive expertise and assessment in medical
      education.

PMID- 24909529
TI  - Exploring the consequences of combining medical students with and without a
      background in biomedical sciences.
AB  - CONTEXT: Medical schools have tended to admit students with strong backgrounds in
      the biomedical sciences. Previous studies have shown that those with backgrounds
      in the social sciences can be as successful in medical school as those with
      science backgrounds. However, the experience of being a 'non-science' student
      over time has not been well described. METHODS: A mixed-methods study was
      developed and run with the aim of elucidating the personal experiences of science
      and non-science students at our institution. Data were generated from a student
      survey that focused on participants' self-identification as science or non
      science students, and on their sense of preparedness and stress, and from a
      series of student focus groups exploring participants' experiences of science and
      non-science issues in all aspects of their training. Descriptive statistics were
      generated for structured survey data. Focus group data and unstructured survey
      data were analysed to identify common themes. End-of-module and end-of-year
      examination data for the four class cohorts in the programme were also analysed
      to compare science and non-science student performance over time. RESULTS: There
      were clear differences between the experiences and performance of science and non
      science students. We found dichotomies in students' self-reported sense of
      preparedness and stress levels, and marked differences in their examination
      performance, which diminished over time to converge around the third year of
      their studies. Combining science and non-science students in the same class
      affected the students to different extents and in different ways. The potential
      disruption of mixing science and non-science students diminished as their levels
      of performance converged. CONCLUSIONS: The psychosocial stress experienced by non
      science students and the challenges it posed, in both their academic and their
      personal lives, have implications for how such students should be supported, and
      how curricula can be configured to afford quality learning for all medical
      students.

PMID- 24909530
TI  - Online testable concept maps: benefits for learning about the pathogenesis of
      disease.
AB  - CONTEXT: Concept maps have been used to promote meaningful learning and critical
      thinking. Although these are crucially important in all disciplines, evidence for
      the benefits of concept mapping for learning in medicine is limited. METHODS: We
      performed a randomised crossover study to assess the benefits of online testable
      concept maps for learning in pathology by volunteer junior medical students.
      Participants (n = 65) were randomly allocated to either of two groups with
      equivalent mean prior academic performance, in which they were given access to
      either online maps or existing online resources for a 2-week block on renal
      disease. Groups then crossed over for a 2-week block on hepatic disease. Outcomes
      were assessed using timed online quizzes, which included questions unrelated to
      topics in the pathogenesis maps as an internal control. Questionnaires were
      administered to evaluate students' acceptance of the maps. RESULTS: In both
      blocks, the group with access to pathogenesis maps achieved significantly higher
      average scores than the control group on quiz questions related to topics covered
      by the maps (Block 1: p < 0.001, Cohen's d = 0.9; Block 2: p = 0.008, Cohen's d =
      0.7). However, mean scores on unrelated questions did not differ significantly
      between the groups. In a third block on pancreatic disease, both groups received
      pathogenesis maps and collectively performed significantly better on quiz topics
      related to the maps than on unrelated topics (p < 0.01, Cohen's d = 0.5).
      Regression analysis revealed that access to pathogenesis maps was the dominant
      contributor to variance in performance on map-related quiz questions. Responses
      to questionnaire items on pathogenesis maps were overwhelmingly positive in both
      groups. CONCLUSIONS: These results indicate that online testable pathogenesis
      maps are well accepted and can improve learning of concepts in pathology by
      medical students.

PMID- 24909531
TI  - Do peer-tutors perform better in examinations? An analysis of medical school
      final examination results.
AB  - CONTEXT: Peer-assisted learning (PAL) is recognised as an effective learning tool
      and its benefits are well documented in a range of educational settings. Learners
      find it enjoyable and their performances in assessments are comparable with those
      of students taught by faculty tutors. In addition, PAL tutors themselves report
      the development of improved clinical skills and confidence through tutoring.
      However, whether tutoring leads to actual improvement in performance has not been
      fully investigated. OBJECTIVES: As high-achieving students are already en route
      to succeeding in final examinations, we wanted to examine whether participation
      in a peer-tutoring programme in itself leads to better final-year examination
      performance. METHODS: We conducted a retrospective analysis of results on final
      year written and clinical examinations at University College London Medical
      School during 2010-2012. Z-scores were calculated and the performances of PAL
      tutors and students who were not PAL tutors were compared using analysis of
      covariance (ancova). Year 4 examination results were used as indicators of
      previous academic attainment. RESULTS: Of the 1050 students who attempted the
      final examination, 172 were PAL tutors in the final year. Students who acted as
      PAL tutors outperformed students who did not in all examination components by 1
      3%. Z-scores differed by approximately 0.2 and this was statistically
      significant, although the significance of this difference diminished when
      controlling for Year 4 results. Students who acted as PAL tutors who had scored
      in the top quartile in Year 4 examinations scored significantly better in a long
      station objective structured clinical examination (LSO). CONCLUSIONS: Although
      students who acted as PAL tutors performed better than students who did not in
      final-year examinations, this difference was small and attributable to the
      students' background academic abilities. High-achieving students appear to be
      self-selecting as peer-tutors and their enhanced performance in LSOs may reflect
      their inherent academic abilities. Although peer-tutoring in itself did not lead
      to enhanced examination performance, further studies are required as many
      factors, such as the proximity of examinations and previous tutoring, can
      potentially affect the relationship between peer-tutoring experience and
      examination performance.

PMID- 24909532
TI  - Dyad practice is efficient practice: a randomised bronchoscopy simulation study.
AB  - CONTEXT: Medical simulation training requires effective and efficient training
      strategies. Dyad practice may be a training strategy worth pursuing because it
      has been proven effective and efficient in motor skills learning. In dyad
      practice two participants collaborate in learning a task they will eventually
      perform individually. In order to explore the effects of dyad practice in a
      medical simulation setting, this study examined the effectiveness and efficiency
      of dyad practice compared with individual practice in the learning of
      bronchoscopy through simulation-based training. METHODS: A total of 36 students
      of medicine were randomly assigned to either individual practice or dyad
      practice. The training setting included video-based instruction, 10 bronchoscopy
      simulator cases and instructor feedback. Participants in the dyad practice group
      alternated between physical and observational practice and hence physically
      undertook only half of the training cases undertaken by participants who
      practised individually. Pre-, post- and delayed (3 weeks) retention tests were
      used to assess skills according to previously validated simulator measures. Data
      were analysed using repeated-measures analysis of variance (anova) on each
      dependent measure. RESULTS: A significant main effect of test was found for all
      measures (F2,67  > 23.32, p < 0.001), indicating improvement in performance from
      pre-tests to post-tests and retention tests. No interaction was found between
      test and group (F2,67  < 0.26, p > 0.49), indicating parallel learning curves.
      Most importantly, no main effect of group was found for any of the measures,
      indicating no difference between learning curves (F1,34  = 2.08, p < 0.16).
      CONCLUSIONS: Individual practice and dyad practice did not differ in their
      effectiveness for the acquisition of bronchoscopy skills through supervised
      simulation training. However, dyad practice proved more efficient than individual
      practice because two participants practising in dyads learned as much as one
      participant practising individually but required the same instructor resources
      and training time as the single learner.

PMID- 24909533
TI  - Learning culture and feedback: an international study of medical athletes and
      musicians.
AB  - OBJECTIVES: Feedback should facilitate learning, but within medical education it
      often fails to deliver on its promise. To better understand why feedback is
      challenging, we explored the unique perspectives of doctors who had also trained
      extensively in sport or music, aiming to: (i) distinguish the elements of the
      response to feedback that are determined by the individual learner from those
      determined by the learning culture, and (ii) understand how these elements
      interact in order to make recommendations for improving feedback in medical
      education. METHODS: Using a constructivist grounded theory approach, we conducted
      semi-structured interviews with 27 doctors or medical students who had high-level
      training and competitive or performance experience in sport (n = 15) or music (n
      = 12). Data were analysed iteratively using constant comparison. Key themes were
      identified and their relationships critically examined to derive a conceptual
      understanding of feedback and its impact. RESULTS: We identified three essential
      sources of influence on the meaning that feedback assumed: the individual
      learner; the characteristics of the feedback, and the learning culture.
      Individual learner traits, such as motivation and orientation toward feedback,
      appeared stable across learning contexts. Similarly, certain feedback
      characteristics, including specificity, credibility and actionability, were
      valued in sport, music and medicine alike. Learning culture influenced feedback
      in three ways: (i) by defining expectations for teachers and teacher-learner
      relationships; (ii) by establishing norms for and expectations of feedback, and
      (iii) by directing teachers' and learners' attention toward certain dimensions of
      performance. Learning culture therefore neither creates motivated learners nor
      defines 'good feedback'; rather, it creates the conditions and opportunities that
      allow good feedback to occur and learners to respond. CONCLUSIONS: An adequate
      understanding of feedback requires an integrated approach incorporating both the
      individual and the learning culture. Our research offers a clear direction for
      medicine's learning culture: normalise feedback; promote trusting teacher-learner
      relationships; define clear performance goals, and ensure that the goals of
      learners and teachers align.

PMID- 24909534
TI  - In-training evaluations: developing an automated screening tool to measure report
      quality.
AB  - OBJECTIVES: In-training evaluation (ITE) is used to assess resident competencies
      in clinical settings. This assessment is documented on an evaluation report (In
      Training Evaluation Report [ITER]). Unfortunately, the quality of these reports
      can be questionable. Therefore, training programmes to improve report quality are
      common. The Completed Clinical Evaluation Report Rating (CCERR) was developed to
      assess completed report quality and has been shown to do so in a reliable manner,
      thus enabling the evaluation of these programmes. The CCERR is a resource
      intensive instrument, which may limit its use. The purpose of this study was to
      create a screening measure (Proxy-CCERR) that can predict the CCERR outcome in a
      less resource-intensive manner. METHODS: Using multiple regression, the authors
      analysed a dataset of 269 ITERs to create a model that can predict the associated
      CCERR scores. The resulting predictive model was tested on the CCERR scores for
      an additional sample of 300 ITERs. RESULTS: The quality of an ITER, as measured
      by the CCERR, can be predicted using a model involving only three variables (R(2)
      = 0.61). The predictive variables included the total number of words in the
      comments, the variability of the ratings and the proportion of comment boxes
      completed on the form. CONCLUSIONS: It is possible to model CCERR scores in a
      highly predictive manner. The predictive variables can be easily extracted in an
      automated process. Because this model is less resource-intensive than the CCERR,
      it makes it possible to provide feedback from ITER training programmes to large
      groups of supervisors and institutions, and even to create automated feedback
      systems using Proxy-CCERR scores.

PMID- 24909535
TI  - Active learning, the accreditation process and 20-something students.

PMID- 24909536
TI  - Relationship between vitamin D, parathyroid hormone, bone mineral density,
      fracture and antiretroviral therapy in HIV patients.
AB  - BACKGROUND: Vitamin D deficiency and abnormal bone mineral density (BMD) have
      been reported in HIV patients. We aimed to find out the effects of antiretroviral
      therapy (ART) on serum vitamin D, parathyroid hormone (PTH) levels, BMD changes
      and fragility fracture rates in HIV patients. METHODS: We collected information
      about baseline demography, risk factors for fracture, viral load (VL), CD4 count,
      serum 25-OH vitamin D (n=357), PTH (n=277), phosphate, ionised calcium,
      creatinine and BMD of spine and hip by DEXA scan (hologic, n=142). Statistical
      analysis used one-way ANOVA followed by Dunn's multiple comparison tests. Results
      Table 1: Total 357 patients, mean age 41.1 (+/- 11.9) years, 249 (66%) black
      African, 197(52%) females, baseline CD4 count 451 (+/- 184) cells/dl, VL 1.4 log
      (+/- 1.2) copies/ml, duration of ART 52 (+/- 35) months were included in the
      analysis. Serum vitamin D was 15.3 (+/- 11.0) ng/ml, PTH (intact) 5.5 (+/- 3.9)
      pmol/l, corrected calcium 2.13 (+/- 0.9), phosphate 1.0 (+/- 0.2) and creatinine
      was 73.4 (+/- 21.1) mmol/l. Ninety four (66%) patients had abnormal BMD (T-score
      of spine or hip or both <= 1.0). Vitamin D levels were deficient (< 30 ng/ml) in
      297 (78.7%) and PTH was high (>4.1 pmol/l) in 177 (64.8%) patients. Of 91 (30.9%)
      patients who had vitamin D levels below 10.0 ng/mL, PTH was high in 70 (n=91,
      76.9%) and abnormal BMD in 50 (n=61, 75.4%) patients. Thirteen patients (3.2%)
      had possible fragility fractures. Tenofovir (TDF) users had higher PTH (P=0.002)
      and lower BMD of spine (0.01) and hip (0.002) and efavirenz (EFV) users had lower
      vitamin D (0.01) levels. On multivariate analysis including all significant
      variables, female sex (OR 1.5 CI 1.3-5.9), age over 40 years (OR 1.2 CI 0.9-5.1)
      and TDF use (OR 1.9 CI 1.6-6.9) were associated with abnormal BMD of hip but not
      spine. CONCLUSION: Female patients over 40 years old on tenofovir containing
      regimens may have increased risk of BMD loss from hip. Whether Vitamin D
      replacement will prevent further bone loss needs further work.

PMID- 24909537
TI  - New developments in biological markers of bone metabolism in osteoporosis.
AB  - Over the last 15 years several biological markers of bone turnover have been
      developed with increased specificity and sensitivity. In osteoporosis clinical
      studies, the IOF and IFCC organizations have recently recommended the
      measurements of serum type I collagen N-propeptide (PINP) and the crosslinked C
      terminal telopeptide (serum CTX) as markers of bone formation and bone
      resorption, respectively. However these markers have some limitations including a
      lack of specificity for bone tissue, their inability to reflect osteocyte
      activity or periosteal apposition. In addition they do not allow the
      investigation of bone tissue quality an important determinant of skeletal
      fragility. To address these limitations, new developments in markers of bone
      metabolism have been recently achieved. These include assays for periostin, a
      matricellular protein preferentially localized in the periosteal tissue,
      sphingosine 1-phosphate, a lipid mediator which acts mainly on osteoclastogenesis
      and the osteocyte factors such as sclerostin and FGF-23. Recent studies have
      shown an association between the circulating levels of these biological markers
      and fracture risk in postmenopausal women or elderly men, although data require
      confirmation in additional prospective studies. Finally, recent studies suggest
      that the measurements of circulating microRNAs may represent a novel class of
      early biological markers in osteoporosis. It is foreseen that with the use of
      genomics and proteomics, new markers will be developed to ultimately improve the
      management of patients with osteoporosis.

PMID- 24909538
TI  - Determinants associated with bone mineral density increase in response to daily
      teriparatide treatment in patients with osteoporosis.
AB  - INTRODUCTION: Several factors associated with bone mineral density (BMD) increase
      are reported with daily teriparatide treatment, but there has been no systematic
      analysis to summarize these associations. The purpose of this study was to
      investigate the clinical determinants associated with BMD increase to daily
      teriparatide treatment. METHODS: This was a retrospective study. We performed an
      analysis of 306 patients diagnosed with osteoporosis. Teriparatide was
      administered at 20MUg/day for 12months. The primary efficacy measure was a change
      in lumbar spine (LS) BMD from baseline at 12months. To determine the response
      variables of BMD changes, we investigated the clinical determinants using
      univariate and multivariate analyses. RESULTS: There was a 9.8+/-8.2% increase in
      LS BMD after 12months. Prior bisphosphonate treatment and baseline procollagen
      type I N-terminal propeptide (PINP) concentration were significantly associated
      with LS BMD absolute response by univariate analyses. In the multiple regression
      model, patients with higher baseline PINP concentration had a significantly
      greater LS BMD absolute increase. Prior bisphosphonate use lost its correlation
      in the multiple regression models. CONCLUSION: Our results showed that baseline
      PINP concentration was a useful predictor of LS BMD absolute increase regardless
      of prior treatment.

PMID- 24909539
TI  - Contractile elements in muscular fascial tissue - implications for in-vitro
      contracture testing for malignant hyperthermia.
AB  - Malignant hyperthermia is a dreaded complication of general anaesthesia.
      Predisposed individuals can be identified using the standardised
      caffeine/halothane in-vitro contracture test on a surgically dissected skeletal
      muscle specimen. Skeletal muscle is composed of muscle fibres and interwoven
      fascial components. Several malignant hyperthermia-associated neuromuscular
      diseases are associated with an altered connective tissue composition. We
      analysed adjacent fascial components of skeletal muscle histologically and
      physiologically. We investigated whether the fascial tissue is sensitive to
      electrical or pharmacological stimulation in a way similar to the in-vitro
      contracture test for diagnosing malignant hyperthermia. Using immunohistochemical
      staining, alpha-smooth muscle actin-positive cells (myofibroblasts) were detected
      in the epi-, endo- and perimysium of human fascial tissue. Force measurements on
      isolated fascial strips after pharmacological challenge with mepyramin revealed
      that myofascial tissue is actively regulated by myofibroblasts, thereby
      influencing the biomechanical properties of skeletal muscle. Absence of
      electrical reactivity and insensitivity to caffeine and halothane suggests that,
      reassuringly, the malignant hyperthermia diagnostic in-vitro contracture test is
      not influenced by the muscular fascial tissue. 

PMID- 24909541
TI  - Long-term treatment patterns of testosterone replacement medications.
AB  - INTRODUCTION: Testosterone replacement therapy (TRT) is prescribed to men
      diagnosed with hypogonadism to alleviate symptoms, improve quality of life, and
      improve overall health. However, most men use TRT for only a short duration. AIM:
      To evaluate the long-term treatment patterns in hypogonadal men using topical TRT
      or short-lasting TRT injections. METHODS: Using the Truven MarketScan((r))
      Database, 15,435 men who received their first (index) topical TRT prescription
      and 517 men who received their short-lasting TRT injection index prescription in
      2009 were followed from 12 to 30 months after treatment initiation. Treatment
      interruption was defined as a medication gap of >30 days. Patients who remained
      off treatment were classified as having discontinued treatment. Patients who
      restarted therapy after 30 days were classified as cyclic users. Patients were
      required to have continuous insurance coverage during 1 year prior to treatment
      initiation and at least 1 year afterward. MAIN OUTCOME MEASURES: Main outcome
      measures were length of therapy, discontinuation, and restarts of topical TRT or
      short-lasting TRT injections. RESULTS: The patient characteristics were similar
      for patients who received topical TRT or short-lasting TRT injections. Of the
      patients who discontinued therapy during the follow-up period, the percentages of
      patients who were still on therapy after 3 months were 52% and 31% for topical
      TRT and short-lasting TRT users, respectively. For cyclic users, there was an
      attrition rate of approximately 40% to 50% of patients in each cycle. For both
      topical TRT and short-lasting TRT injections, the gap between stopping and
      restarting therapy tended to decrease over time. CONCLUSIONS: In this analysis,
      high discontinuation rates were observed. The treatment pattern of TRT may be
      related to the disease state rather than dosing, daily use, or mode of
      administration.

PMID- 24909542
TI  - Genetic variations of NLRP1: susceptibility in psoriasis.
AB  - BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the
      inflammasome multiprotein complex involved in the production of interleukin (IL)
      1beta and IL-18, two cytokines strongly implicated in psoriasis pathogenesis.
      Genetic variations in NLRP1 are associated with a predisposition for chronic
      inflammatory conditions. OBJECTIVES: The aim of the study was to investigate the
      role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.
      MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms
      (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by
      TaqMan allelic discrimination in a patient sample comprising 1847 individuals
      from 478 families and 802 healthy controls. RESULTS: Using the transmission
      disequilibrium test, a significant increase in the transmission of the NLRP1
      rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P =
      0.006 and P = 0.033, respectively). Furthermore, homozygosity for the rs878329C
      allele correlated with a younger age of onset. We also observed an increase in
      the expression of NLRP1 mRNA in the peripheral blood cells of patients with
      psoriasis. This was accompanied by a higher level of circulating IL-18 and
      appeared to be associated with the rs878329C allele. CONCLUSIONS: Our data
      support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis
      susceptibility and further support the role of innate immunity in psoriasis.

PMID- 24909543
TI  - Cutaneous melanoma in Iceland: changing Breslow's tumour thickness.
AB  - BACKGROUND: The incidence of cutaneous melanoma increased dramatically in Iceland
      during the last two decades of the 20th century. OBJECTIVE: The aim of this study
      was to investigate the trend in Breslow's tumour thickness during the years 1980
      2009. METHODS: The population-based Icelandic Cancer Registry provided
      information on all cutaneous melanomas diagnosed in the country during the study
      period, a total of 854 cases. Incidence rates were stratified according to
      gender, age at diagnosis, year of diagnosis and Breslow's tumour thickness.
      RESULTS: When stratified by gender and age, the incidence of thin (<=1.0 mm)
      melanomas increased dramatically in all subgroups. The increase in thin (<=1.0
      mm) melanomas was more apparent in women or 2.6 per 100,000 in 1980-1989 to 13.3
      in 2000-2009 and especially in young (<50 years) women or from 1.6 to 12.2 per
      100,000 during the same period compared to an increase from 0.2 to 3.4 per
      100,000 for young (<50 years) men (P < 0.05). In intermediate thickness (1.01-4.0
      mm) tumours, the incidence increased only in men over the age of 50 from 2.1 in
      1980-1989 to 11.3 per 100,000 in 2000-2009 (P < 0.05). The incidence of thick
      melanomas (>4 mm) did not increase. The median Breslow's thickness declined from
      2.15 mm in 1980-1989 to 0.9 mm in 2000-2009 in males and from 1.0 to 0.6 mm in
      females for the same period (P < 0.001). CONCLUSION: The rise in melanoma
      incidence in individuals under 50 years and in women over 50 years was confined
      to thin tumours. However, among older males there was also an increased incidence
      of tumours of an intermediate thickness. This could indicate that future melanoma
      educational campaigns in Iceland should be directed at older individuals, and
      that older men may need special attention regarding suspicious nevi.

PMID- 24909540
TI  - Distinct actions of Rab3 and Rab27 GTPases on late stages of exocytosis of
      insulin.
AB  - Rab GTPases associated with insulin-containing secretory granules (SGs) are key
      in targeting, docking and assembly of molecular complexes governing pancreatic
      beta-cell exocytosis. Four Rab3 isoforms along with Rab27A are associated with
      insulin granules, yet elucidation of the distinct roles of these Rab families on
      exocytosis remains unclear. To define specific actions of these Rab families we
      employ Rab3GAP and/or EPI64A GTPase-activating protein overexpression in beta
      cells from wild-type or Ashen mice to selectively transit the entire Rab3 family
      or Rab27A to a GDP-bound state. Ashen mice carry a spontaneous mutation that
      eliminates Rab27A expression. Using membrane capacitance measurements we find
      that GTP/GDP nucleotide cycling of Rab27A is essential for generation of the
      functionally defined immediately releasable pool (IRP) and central to regulating
      the size of the readily releasable pool (RRP). By comparison, nucleotide cycling
      of Rab3 GTPases, but not of Rab27A, is essential for a kinetically rapid filling
      of the RRP with SGs. Aside from these distinct functions, Rab3 and Rab27A GTPases
      demonstrate considerable functional overlap in building the readily releasable
      granule pool. Hence, while Rab3 and Rab27A cooperate to generate release-ready
      SGs in beta-cells, they also direct unique kinetic and functional properties of
      the exocytotic pathway. 

PMID- 24909544
TI  - Protective buttressing of the hominin face.
AB  - When humans fight hand-to-hand the face is usually the primary target and the
      bones that suffer the highest rates of fracture are the parts of the skull that
      exhibit the greatest increase in robusticity during the evolution of basal
      hominins. These bones are also the most sexually dimorphic parts of the skull in
      both australopiths and humans. In this review, we suggest that many of the facial
      features that characterize early hominins evolved to protect the face from injury
      during fighting with fists. Specifically, the trend towards a more orthognathic
      face; the bunodont form and expansion of the postcanine teeth; the increased
      robusticity of the orbit; the increased robusticity of the masticatory system,
      including the mandibular corpus and condyle, zygoma, and anterior pillars of the
      maxilla; and the enlarged jaw adductor musculature are traits that may represent
      protective buttressing of the face. If the protective buttressing hypothesis is
      correct, the primary differences in the face of robust versus gracile
      australopiths may be more a function of differences in mating system than
      differences in diet as is generally assumed. In this scenario, the evolution of
      reduced facial robusticity in Homo is associated with the evolution of reduced
      strength of the upper body and, therefore, with reduced striking power. The
      protective buttressing hypothesis provides a functional explanation for the
      puzzling observation that although humans do not fight by biting our species
      exhibits pronounced sexual dimorphism in the strength and power of the jaw and
      neck musculature. The protective buttressing hypothesis is also consistent with
      observations that modern humans can accurately assess a male's strength and
      fighting ability from facial shape and voice quality. 

PMID- 24909547
TI  - Chemically resolved transient collision events of single electrocatalytic
      nanoparticles.
AB  - Here we report the use of fast-scan cyclic voltammetry (FSCV) to study transient
      collision and immobilization events of single electrocatalytic metal
      nanoparticles (NPs) on an inert electrode. In this study, a fast, repetitive
      voltage signal is continuously scanned on an ultramicroelectrode and its faradaic
      signal is recorded. Electrocatalytically active metal NPs are allowed to collide
      and immobilize on the electrode resulting in the direct recording of the
      transient voltammetric response of single NPs. This approach enables one to
      obtain the transient voltammetric response and electrocatalytic effects of single
      catalytic NPs as they interact with an inert electrode. The use of FSCV has
      enabled us to obtain chemical information, which is otherwise difficult to study
      with previous amperometric methods. 

PMID- 24909545
TI  - Primary aldosteronism in hypertensive patients: clinical implications and target
      therapy.
AB  - BACKGROUND: The prevalence of primary aldosteronism (PA) in hypertensive patients
      varies according to diagnostic testing and ascertained normal cut-offs. The aim
      of this case-control study was to confirm the high prevalence of PA in a large
      hypertensive population and evaluate the antihypertensive effect of
      mineralocorticoid receptor antagonists (MRA) treatment. MATERIAL AND METHODS: We
      investigated 327 hypertensive and 90 matched normotensive subjects with normal
      adrenal imaging. Serum aldosterone (ALD), active renin (REN) levels and
      aldosterone/active renin (ALD/REN) ratio were measured before and after a
      combined sodium chloride, fludrocortisone and dexamethasone suppression test
      (FDST). Post-FDST values were compared to cut-offs obtained from controls (post
      FDST ALD 2.96 ng/dL and post-FDST ALD/REN 0.93 ng/dL/MUU/mL). PA patients
      received MRA treatment. RESULTS: By applying the combination of post-FDST ALD
      levels and ALD/REN ratio, 28.7% of the hypertensive patients had PA. There was a
      positive, albeit weak, correlation between systolic (SBP) and diastolic blood
      pressure (DBP) and ALD levels and/or ALD/REN ratio after the FDST (P < 0.0001).
      SBP was associated with a post-FDST ALD of 3.24 ng/dL and ALD/REN ratio of 0.90
      ng/dL/MUU/mL, whereas post-FDST ALD had an inverse association at serum K+ values
      of less than 3.9 mEq/L. MRA treatment in 69 PA patients, resulted in a
      significant reduction in the maximum SBP and DBP values (28 +/- 15 and 14 +/- 7
      mmHg, respectively, P < 0.0001). CONCLUSIONS: Using the FDST, an increased
      prevalence of PA in hypertensives was observed. Alpha significant blood pressure
      lowering effect was obtained with MRA treatment, implying that these agents may
      be beneficial in a significant number of hypertensive patients.

PMID- 24909546
TI  - A multicenter prospective trial to asses a new real-time polymerase chain
      reaction for detection of Treponema pallidum, herpes simplex-1/2 and Haemophilus
      ducreyi in genital, anal and oropharyngeal ulcers.
AB  - Treponema pallidum, herpes simplex virus types 1 or 2 (HSV-1/2) and Haemophilus
      ducreyi are sexually transmitted pathogens that can cause genital, anal and
      oropharyngeal ulcers. Laboratory evaluation of these pathogens in ulcers requires
      different types of specimens and tests, increasing the risk of improper specimen
      handling and time lapse until analysis. We sought to develop a new real-time PCR
      (TP-HD-HSV1/2 PCR) to facilitate the detection of T. pallidum, HSV-1/2 and H.
      ducreyi in ulcers. The TP-HD-HSV1/2 PCR was tested (i) in a retrospective study
      on 193 specimens of various clinical origin and (ii) in a prospective study on 36
      patients with genital, anal or oropharyngeal ulcers (ClinicalTrials.gov #
      NCT01688258). The results of the TP-HD-HSV1/2 PCR were compared with standard
      diagnostic methods (T. pallidum: serology, dark field microscopy; HSV-1/2: PCR;
      H. ducreyi: cultivation). Sensitivity and specificity of the TP-HD-HSV1/2 PCR for
      T. pallidum were both 100%, for HSV-1 100% and 98%, and for HSV-2 100% and 98%,
      respectively. T. pallidum and HSV-1/2 were detected in 53% and 22% of patients in
      the prospective study; H. ducreyi was not detected. In the prospective study,
      5/19 (26%) specimens were true positive for T. pallidum in the TP-HD-HSV1/2 PCR
      but non-reactive in the VDRL. The TP-HD-HSV1/2 PCR is sensitive and specific for
      the detection of T. pallidum and HSV-1/2 in routine clinical practice and it
      appears superior to serology in early T. pallidum infections. 

PMID- 24909548
TI  - In situ and laboratory toxicity of coalbed natural gas produced waters with
      elevated sodium bicarbonate.
AB  - Some tributaries in the Powder River Structural Basin, USA, were historically
      ephemeral, but now contain water year round as a result of discharge of coalbed
      natural gas (CBNG)-produced waters. This presented the opportunity to study field
      sites with 100% effluent water with elevated concentrations of sodium
      bicarbonate. In situ experiments, static renewal experiments performed
      simultaneously with in situ experiments, and static renewal experiments performed
      with site water in the laboratory demonstrated that CBNG-produced water reduces
      survival of fathead minnow (Pimephales promelas) and pallid sturgeon
      (Scaphirhynchus albus). Age affected survival of fathead minnow, where fish 2 d
      posthatch (dph) were more sensitive than 6 dph fish, but pallid sturgeon survival
      was adversely affected at both 4 and 6 dph. This may have implications for acute
      assays that allow for the use of fish up to 14 dph. The survival of early
      lifestage fish is reduced significantly in the field when concentrations of
      NaHCO(3) rise to more than 1500 mg/L (also expressed as >1245 mg HCO(3) (-) /L).
      Treatment with the Higgin's Loop technology and dilution of untreated water
      increased survival in the laboratory. The mixing zones of the 3 outfalls studied
      ranged from approximately 800 m to 1200 m below the confluence. These experiments
      addressed the acute toxicity of effluent waters but did not address issues
      related to the volumes of water that may be added to the watershed.

PMID- 24909550
TI  - Zosteriform metastases of eccrine porocarcinoma mimicking eruptive seborrhoeic
      keratoses.

PMID- 24909549
TI  - Randomized phase III study of 2 cisplatin-based chemoradiation regimens in
      locally advanced head and neck squamous cell carcinoma: impact of changing
      disease epidemiology on contemporary trial design.
AB  - BACKGROUND: Chemoradiotherapy results in excellent outcomes in locally advanced
      head and neck squamous cell carcinoma (HNSCC). This trial compared 2
      chemoradiotherapy regimens. METHODS: Patients with locally advanced HNSCC were
      treated with radiation (70-74.4 Gy), and randomized to arm A: cisplatin 100
      mg/m(2) on radiotherapy (RT) days 1, 22, and 43, or arm B: cisplatin (20 mg/m(2)
      /day) and 5-fluorouracil (5-FU; 1000 mg/m(2) /day) continuous 96-hour infusions
      on RT weeks 1 and 4. The primary endpoint was relapse-free survival (RFS).
      RESULTS: Between February 2008 and October 2011, 69 patients were enrolled in
      this study. The study prematurely closed when a scheduled interim analysis showed
      superior outcomes in both arms and futility of continuation. Eighty-three percent
      of patients had oropharyngeal cancer, of these, 86% were human papillomavirus
      (HPV)/p16+. The 3-year Kaplan-Meier outcome estimates (median follow-up, 41
      months) for arms A and B were: RFS 87% versus 80% (p = .24), overall survival 97%
      versus 85% (p = .013), locoregional control 96% versus 94% (p = .52), and distant
      metastatic control 91% versus 87% (p = .9). CONCLUSION: Multiagent was not
      superior to single-agent chemoradiotherapy. Overrepresentation of HPV/p16+
      patients resulted in better than expected outcomes.

PMID- 24909551
TI  - Prevalence of human T-lymphotropic virus type 1 carriers among pregnant women in
      Hokkaido, Japan.
AB  - As there is a risk of MTCT of HTLV-1, the HSGP HTLV-1 MTCT was organized in 2011.
      To determine how many pregnant women are infected with HTLV-1 in Hokkaido, which
      is the northernmost and the second largest island in Japan with a population of
      5,467,000 and 39,392 newborns in 2011, the HSGP HTLV-1 MTCT asked all facilities
      that may care for pregnant women in Hokkaido in July 2013 to provide information
      on the number of pregnant women who underwent screening for anti-HTLV-1 antibody
      using particle agglutination or chemiluminescent enzyme immunoassay, and the
      numbers of those with positive, equivocal, and negative test results in the
      screening and confirmation tests using western blotting or PCR methods in 2012,
      respectively. A total of 111 facilities participated in this study and provided
      information on 33,617 pregnant women who underwent screening in 2012,
      corresponding to approximately 85% of all pregnant women who gave birth in
      Hokkaido in 2012. Of 81 candidates for a confirmation test because of positive (n
      = 77) or equivocal (n = 4) results on screening, 63 (78%) underwent the
      confirmation test and, finally, 34 (0.1%) and 33,563 (99.8%) women were judged to
      be HTLV-1 carriers and non-carriers, respectively. It was concluded that the
      prevalence rate of HTLV-1 carriers was low, one per 1000 pregnant women in
      Hokkaido. Approximately 40 infants are born yearly to mothers infected with HTLV
      1 in Hokkaido.

PMID- 24909552
TI  - Captides: rigid junctions between beta sheets and small molecules.
AB  - An extensive series of covalently linked small molecule-peptide adducts based on
      a terminally capped-beta hairpin motif is reported. The constructs can be
      prepared by standard solid-phase Fmoc chemistry with one to four peptide chains
      linked to small molecule hubs bearing carboxylic acid moieties. The key feature
      of interest is the precise, buried environment of the small molecule, and its
      rigid orientation relative to one or more short but fully structured peptide
      chain(s). Most of this study employs a minimalist nine residue 'captide', a
      capped beta-turn, but we illustrate general applicability to peptides which can
      terminate in a beta strand. The non-peptide portion of these adducts can include
      nearly any molecule bearing one or more carboxylic acid groups. Fold-dependent
      rigidity sets this strategy apart from the currently available bioconjugation
      methods, which typically engender significant flexibility between peptide and
      tag. Applications to catalyst enhancement, drug design, higher-order assembly,
      and FRET calibration rulers are discussed.

PMID- 24909553
TI  - Block copolymer-derived monolithic polymer films and membranes comprising self
      organized cylindrical nanopores for chemical sensing and separations.
AB  - Microphase separation of block copolymers (BCPs) has been extensively studied
      because it leads to the self-assembled formation of periodic structures
      controlled on the scale of tens of nanometers. In particular, BCP-derived
      cylindrical microdomains have attracted considerable interest for various
      applications owing to their well-defined shapes of uniform and tunable diameters.
      This focus review highlights recent efforts to apply BCP-derived monolithic
      films/membranes comprising cylindrical nanopores for chemical sensing and
      separations. The nanopores provide confined molecular pathways that exhibit
      enhanced selectivity based on steric, electrostatic, and chemical interactions,
      and thus, enable us to design unique electrochemical sensors and highly efficient
      separation membranes. 

PMID- 24909554
TI  - Seeking carotenoid pigments in amber-preserved fossil feathers.
AB  - Plumage colours bestowed by carotenoid pigments can be important for visual
      communication and likely have a long evolutionary history within Aves.
      Discovering plumage carotenoids in fossil feathers could provide insight into the
      ecology of ancient birds and non-avian dinosaurs. With reference to a modern
      feather, we sought chemical evidence of carotenoids in six feathers preserved in
      amber (Miocene to mid-Cretaceous) and in a feather preserved as a compression
      fossil (Eocene). Evidence of melanin pigmentation and microstructure preservation
      was evaluated with scanning electron and light microscopies. We observed fine
      microstructural details including evidence for melanin pigmentation in the amber
      and compression fossils, but Raman spectral bands did not confirm the presence of
      carotenoids in them. Carotenoids may have been originally absent from these
      feathers or the pigments may have degraded during burial; the preservation of
      microstructure may suggest the former. Significantly, we show that carotenoid
      plumage pigments can be detected without sample destruction through an amber
      matrix using confocal Raman spectroscopy. 

PMID- 24909557
TI  - Isolable aryl-substituted silyl radicals: synthesis, characterization, and
      reactivity.
AB  - Isolable aryl-substituted silyl radicals (tBu2 MeSi)2(Ar)Si(.) (Ar = C6H5, 4
      tBuC6H4, 4-PhC6H4, 3,5-tBu2C6H3) were synthesized by the reaction of the
      corresponding iodosilane with an equimolar amount of potassium graphite (KC8 ) in
      tetrahydrofuran (THF). The crystal structure of 3,5-tBu2C6H3 derivative, which
      was determined by X-ray crystallography, showed a planar geometry around the Si
      atom for the radical center. EPR studies of all four radicals revealed the lack
      of the delocalization of the unpaired electron over the aromatic ring. Reactivity
      and spectroscopic studies of the less-hindered phenyl-substituted silyl radical
      showed that it exists as an equilibrium mixture of the radical and its silene
      type dimer in solution.

PMID- 24909555
TI  - Comparative study of ex vivo probe-based confocal laser endomicroscopy and light
      microscopy in lung cancer diagnostics.
AB  - BACKGROUND AND OBJECTIVE: Probe-based confocal laser endoscopy (pCLE) allows for
      real-time non-invasive histological imaging via bronchoscopy. Interpreting CLE
      images and correlating with traditional histopathology remains challenging. We
      performed an ex vivo study to evaluate the correlation between light microscopy
      findings and pCLE imaging of primary lung carcinoma. METHODS: Post-lobectomy
      specimens for lung cancer nodules were examined ex vivo by pCLE. The examined
      areas were marked with brilliant green dye, and the surrounding tissues were
      stained by methylene blue dye. Lung tissue segments were resected and
      histopathological specimens were generated with 50-MUm thickness from the marked
      areas and stained with haematoxylin and eosin. Pathologists and pulmonologists
      reviewed the images for correlating features. RESULTS: Eighteen lobectomy
      specimens from 18 different patients were collected. Three primary features were
      observed in all samples using pCLE in the cancer surroundings: alveolar
      dystelectasis with thickening of alveolar walls, alveolar edema and a large
      amount of macrophages. The stromal and parenchymal components of the studied
      subtypes of non-small-cell lung cancer differed from each other. The stromal
      component for all nine adenocarcinoma specimens had a highly fluorescent field
      penetrated by dark hollows. All six squamous cell carcinoma specimens had the
      stromal component appeared as 'biparously' branching, highly fluorescent fibres.
      No stromal component was observed in any small-cell carcinoma specimen, and at
      low power field, the cellular component was dominant with an observed light
      scattering pattern. CONCLUSIONS: pCLE can identify lung carcinoma in ex vivo
      samples. Certain light microscopy features of lung carcinoma can be visualized
      with pCLE.

PMID- 24909556
TI  - Cardiovascular collapse post chronic total occlusion percutaneous coronary
      intervention due to a compressive left atrial hematoma managed with percutaneous
      drainage.
AB  - This case illustrates a potential complication of the retrograde approach using
      epicardial collaterals for chronic total occlusion (CTO) percutaneous coronary
      intervention (PCI). Hypotension post CTO PCI in a patient who has undergone
      previous cardiac surgery can have multiple causes, one of which is chamber
      compression from a localized hematoma due to coronary perforation as occurred in
      this case. This report is the first description of successful nonsurgical
      management of a left atrial hematoma causing cardiovascular collapse with
      percutaneous drainage.

PMID- 24909558
TI  - Dickkopf-3 alters the morphological response to retinoic acid during neuronal
      differentiation of human embryonal carcinoma cells.
AB  - Dickkopf-3 (Dkk-3) and Dkkl-1 (Soggy) are secreted proteins of poorly understood
      function that are highly expressed in subsets of neurons in the brain. To explore
      their potential roles during neuronal development, we examined their expression
      in Ntera-2 (NT2) human embryonal carcinoma cells, which differentiate into
      neurons upon treatment with retinoic acid (RA). RA treatment increased the mRNA
      and protein levels of Dkk-3 but not of Dkkl-1. Ectopic expression of both Dkk-3
      and Dkkl-1 induced apoptosis in NT2 cells. Gene silencing of Dkk-3 did not affect
      NT2 cell growth or differentiation but altered their response to RA in suspension
      cultures. RA treatment of NT2 cells cultured in suspension resulted in
      morphological changes that led to cell attachment and flattening out of cell
      aggregates. Although there were no significant differences in the expression
      levels of cell adhesion molecules in control and Dkk-3-silenced cells, this
      morphological response was not observed in Dkk-3-silenced cells. These findings
      suggest that Dkk-3 plays a role in the regulation of cell interactions during RA
      induced neuronal differentiation.

PMID- 24909559
TI  - Effect of the addition of chia's by-product on the composition of fatty acids in
      hamburgers through chemometric methods.
AB  - BACKGROUND: Hamburger is a meat-based food that is easy to prepare and is widely
      consumed. It can be enriched using different ingredients, such as chia's by
      product, which is rich in omega-3. Chemometrics is a very interesting tool to
      assess the influence of ingredients in the composition of foods. A complete
      factorial design 2(2) (two factors in two levels) with duplicate was performed to
      investigate the influence of the factors (1) concentration of textured soy
      proteins (TSP) and (2) concentration of chia flour partially defatted (CFPD) as a
      partial replacement for the bovine meat and porcine fat mix in hamburgers.
      RESULTS: The results of proximal composition, lipid oxidation, fatty acids sums,
      ratios, and nutritional indexes were used to propose statistical models. The
      factors TSP and CFPD were significant, and the increased values contributed to
      improve the composition in fatty acids, crude protein, and ash. Principal
      components analysis distinguished the samples with a higher content of chia. In
      desirability analysis, the highest level of TSP and CFPD was described as the
      optimal region, and it was not necessary to make another experimental point.
      CONCLUSION: The addition of chia's by-product is an alternative to increase the
      alpha-linolenic contents and to obtain nutritionally balanced food.

PMID- 24909560
TI  - CCN1 secreted by tonsil-derived mesenchymal stem cells promotes endothelial cell
      angiogenesis via integrin alphav beta3 and AMPK.
AB  - CCN1 is highly expressed in cancer cells and has been identified in the secretome
      of bone marrow-derived mesenchymal stem cells (BM-MSC). Although secreted CCN1 is
      known to promote angiogenesis, its underlying mechanism remains unclear. Here, we
      examined whether our recently-established tonsil-derived MSC (T-MSC) secrete CCN1
      and, if any, how CCN1 promotes the angiogenesis of human umbilical vein
      endothelial cells (HUVEC). Compared with untreated control T-MSC, a higher level
      of CCN1 was secreted by T-MSC treated with activin A and sonic hedgehog, drugs
      known to induce endodermal differentiation. Expectedly, conditioned medium
      collected from differentiated T-MSC (DCM) significantly increased HUVEC migration
      and tube formation compared with that from control T-MSC (CCM), and these
      stimulatory effects were reversed by neutralization with anti-CCN1 antibody.
      Treatment with recombinant human CCN1 (rh-CCN1) alone also mimicked the
      stimulatory effects of DCM. Furthermore, treatment with either DCM or rh-CCN1
      increased the phosphorylation of AMP kinase (AMPK), and ectopic expression of
      siRNA of the AMPK gene inhibited all observed effects of both DCM and rh-CCN1.
      However, no alteration of intracellular ATP levels or phosphorylation of LKB1, a
      well-known upstream factor of AMPK activation, was observed under our conditions.
      Finally, the neutralization of integrin alpha(v) beta(3) with anti-integrin
      alpha(v) beta(3) antibody almost completely reversed the effects of CCN1 on AMPK
      phosphorylation, and EC migration and tube formation. Taken together, we
      demonstrated that T-MSC increase the secretion of CCN1 in response to endodermal
      differentiation and that integrin alpha(v) beta(3) and AMPK mediate CCN1-induced
      EC migration and tube formation independent of intracellular ATP levels
      alteration.

PMID- 24909561
TI  - Evaluation of an immunoassay for determination of plasma efavirenz concentrations
      in resource-limited settings.
AB  - INTRODUCTION: Therapeutic drug monitoring (TDM) may improve antiretroviral
      efficacy through adjustment of individual drug administration. This could result
      in reduced toxicity, prevent drug resistance, and aid management of drug-drug
      interactions. However, most measurement methods are too costly to be implemented
      in resource-limited settings. This study evaluated a commercially available
      immunoassay for measurement of plasma efavirenz. METHODS: The immunoassay-based
      method was applied to measure efavirenz using a readily available Humastar 80
      chemistry analyzer. We compared plasma efavirenz concentrations measured by the
      immunoassay with liquid chromatography tandem mass spectrometry (LC-MS/MS)
      (reference method) in 315 plasma samples collected from HIV patients on
      treatment. Concentrations were categorized as suboptimal<1 ug/ml, normal 1-4
      ug/ml or high>4 ug/ml. Agreement between results of the methods was assessed via
      Bland-Altman plot and kappa statistic values. RESULTS: The median Interquartile
      range (IQR) efavirenz concentration was 2.8 (1.9; 4.5) ug/ml measured by the LC
      MS/MS method and 2.5 (1.8; 3.9) ug/ml by the immunoassay and the results were
      well correlated (rho=0.94). The limits of agreement assessed by Bland-Altman
      plots were -2.54; 1.70 ug/ml. Although immunoassay underestimated high
      concentrations, it had good agreement for classification into low, normal or high
      concentrations (K=0.74). CONCLUSIONS: The immunoassay is a feasible alternative
      to determine efavirenz in areas with limited resources. The assay provides a
      reasonable approximation of efavirenz concentration in the majority of samples
      with a tendency to underestimate high concentrations. Agreement between tests
      evaluated in this study was clinically satisfactory for identification of low,
      normal and high efavirenz concentrations.

PMID- 24909562
TI  - How can bioactive glasses be useful in ocular surgery?
AB  - In the last few decades, the introduction of bioactive glasses (BGs), a special
      class of bioceramics that are able to bond to living tissues stimulating new
      tissue growth, has improved both treatment procedures via reconstructive surgery
      and the quality of life of rehabilitated patients in orthopedics and dentistry.
      While BGs have been extensively investigated for applications in these two
      surgical fields, there has been relatively little research on their use in other
      medical areas. Glass has been used for centuries to produce external refractive
      lenses and the intraocular implantation of small glass disks to correct visual
      deficiencies has been documented since the mid 1700s. Moreover, some evidences
      reported in the recent literature seem to demonstrate that the success of three
      specific types of ophthalmic devices, that is, synthetic grafts for eye orbit
      bone repair, orbital implants replacing the whole ocular globe and
      keratoprostheses (artificial cornea), could significantly benefit by the use of
      BG. A prospective view as well as a state-of-the-art review on this topic are
      currently lacking in the literature. The present article aims to give a
      comprehensive picture of the BG-based implants that have been developed in the
      context of ocular surgery; the strengths and shortcomings of the existing devices
      are outlined in order to provide useful stimuli for future research. Promising
      research directions are also proposed, emphasizing the added values that BGs
      could carry in ophthalmology in the light of recent findings in tissue
      engineering and regenerative medicine.

PMID- 24909563
TI  - Symptom severity and conservative treatment for carpal tunnel syndrome in
      association with eventual carpal tunnel release.
AB  - PURPOSE: To study the relationship between the severity of carpal tunnel syndrome
      (CTS) symptoms and surgery for CTS and the relationship between conservative
      treatments and surgery for CTS. METHODS: A secondary analysis of baseline to 6
      month data from a randomized controlled trial, which examined the effectiveness
      of orthosis/stretch combinations on the symptoms of CTS, was conducted for a
      total of 96 participants with CTS. Participants completed the Carpal Tunnel
      Questionnaire and posttreatment surveys. Statistical analyses included
      exploration of correlates of progression to surgery for CTS and logistical
      regression to examine the association between conservative treatments and CTS
      symptoms and progression to surgery for CTS. RESULTS: Twenty-one participants
      received surgery for their CTS, and 31 participants received 1 or more
      conservative treatments. Severity of baseline CTS symptoms and additional
      treatments were indicators of progression to surgery. The randomized controlled
      trial intervention was inversely associated with progression to surgery.
      CONCLUSIONS: CTS that does not respond to an initial course of conservative
      treatment may not improve with additional treatments. More than half of the
      participants who received additional conservative treatment still progressed to
      surgery. Current intervention guidelines for CTS provide limited guidance as to
      the best methods to efficiently treat CTS. CLINICAL RELEVANCE: CTS is a costly
      and high-burden disorder, resulting in reduced quality of life. Research should
      examine when and for whom conservative care is an effective choice and the
      association between conservative care and the eventual need for CTS surgery.

PMID- 24909564
TI  - Radial collateral ligament injury of the little finger proximal interphalangeal
      joint in young pianists.
AB  - PURPOSE: To report the features of radial collateral ligament injury of the
      little finger proximal interphalangeal joint in young piano players. METHODS:
      Between 2005 and 2012, we treated 6 cases of radial collateral ligament injury of
      the little finger proximal interphalangeal joint in young piano players at a
      single referral center. We conducted a retrospective review of charts and
      radiographs and telephone-interviewed all patients at a mean follow-up of 33
      months (range, 12-66 mo) to evaluate features of this injury. RESULTS: All
      patients were girls with a mean age of 10 years (range, 8-12 y), and all had
      injuries in their right hands. Patients had been playing piano for a mean 3.8
      years (range, 3-5 y) and practicing for a mean 1.8 hours per day (range, 1-3 h).
      Pain was commonly aggravated when they played octaves or advanced pieces
      requiring extensive finger movements. All patients were playing on standard-size
      piano keyboards and had generalized hypermobility with a mean Beighton and Horan
      score of 6.3 (range, 5-9). Two patients had an ulnar deviation deformity of 10
      degrees  and 15 degrees  each at the proximal interphalangeal joint whereas the
      others had no fixed joint deformity. Five patients showed improvement with
      conservative treatment, but 1 patient underwent surgery. CONCLUSIONS: In our
      practice, all piano-related radial collateral ligament injuries were in female
      preadolescents with evidence of generalized hypermobility; patients had been
      playing piano extensively, suggesting that the injury could have resulted from
      stress on the joint during piano playing. Future studies should further evaluate
      the efficacy of modifying keyboard size, techniques, and repertoires for piano
      lessons and of patient education for this type of injury. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 24909565
TI  - Driving with upper extremity immobilization: a comprehensive review.
AB  - Driving with upper extremity immobilization can be potentially dangerous. The aim
      of this article is to review current medical literature, state laws, and
      guidelines on driving with upper extremity immobilization and appraise the
      available evidence. A literature search was conducted to identify citations
      related to driving with upper extremity immobilization and included a law
      literature search. Each state's Department of Motor Vehicle handbook was
      reviewed. Fourteen studies were reviewed and 5 provided subjective and/or
      objective assessments of upper limb immobilization. Of 2 studies that evaluated
      only below-elbow immobilization, 1 found driving in a wrist splint had no
      perceptible effect on driving ability, and the other supported safe driving under
      normal conditions. The studies that evaluated both below- and above-elbow
      immobilization recommended against driving with left arm above-elbow
      immobilization. Two of them found a trend toward worse driving performance in
      both below- and above-elbow splints. The following organizations' policies on
      driving are (1) The American Medical Association and National Highway Traffic
      Association have a joint recommendation for older drivers recommending referral
      to a rehabilitation specialist, (2) the U.S. Public Health Service recommends
      normal motor function and adequate mobility of both upper extremities and a
      performance examination when impaired, and (3) the U.S. Department of
      Transportation recommends a performance evaluation to determine fitness of
      commercial motor vehicle drivers. There are no state statutes or
      multijurisdictional surveys on the topic. This review finds that driving is
      hindered in some splints, there are substantial variations in physician practice
      patterns, there are no formal guidelines for physicians and patients to consider,
      and there is a paucity of published literature on this topic in the United
      States. Both physicians and patients would benefit from evidence-based
      recommendations or practice guidelines. 

PMID- 24909566
TI  - A comparative study of the effects of growth and differentiation factor 5 on
      muscle-derived stem cells and bone marrow stromal cells in an in vitro tendon
      healing model.
AB  - PURPOSE: To investigate the ability of muscle-derived stem cells (MDSCs)
      supplemented with growth and differentiation factor-5 (GDF-5) to improve tendon
      healing compared with bone marrow stromal cells (BMSCs) in an in vitro tendon
      culture model. METHODS: Eighty canine flexor digitorum profundus tendons were
      assigned into 5 groups: repaired tendon (1) without gel patch interposition (no
      cell group), (2) with BMSC-seeded gel patch interposition (BMSC group), (3) with
      MDSC-seeded gel patch interposition (MDSC group), (4) with GDF-5-treated BMSC
      seeded gel patch interposition (BMSC+GDF-5 group), and (5) with GDF-5-treated
      MDSC-seeded gel patch interposition (MDSC+GDF-5 group). After culturing for 2 or
      4 weeks, the failure strength of the healing tendons was measured. The tendons
      were also evaluated histologically. RESULTS: The failure strength of the repaired
      tendon in the MDSC+GDF-5 group was significantly higher than that of the non-cell
      and BMSC groups. The stiffness of the repaired tendons in the MDSC+GDF-5 group
      was significantly higher than that of the non-cell group. Histologically, the
      implanted cells became incorporated into the original tendon in all 4 cell-seeded
      groups. CONCLUSIONS: Interposition of a multilayered GDF-5 and MDSC-seeded
      collagen gel patch at the repair site enhanced tendon healing compared with a
      similar patch using BMSC. However, this increase in vitro was relatively small.
      In the clinical setting, differences between MDSC and BMSC may not be
      substantially different, and it remains to be shown that such methods might
      enhance the results of an uncomplicated tendon repair clinically. CLINICAL
      RELEVANCE: Muscle-derived stem cell implantation and administration of GDF-5 may
      improve the outcome of tendon repair.

PMID- 24909567
TI  - Distinct effects of methotrexate and etanercept on the B cell compartment in
      patients with juvenile idiopathic arthritis.
AB  - OBJECTIVE: B cells have been shown to play an important role in the pathogenesis
      of rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Current
      treatments include the disease-modifying antirheumatic drugs methotrexate (MTX)
      and tumor necrosis factor alpha inhibition with etanercept. This study was
      undertaken to determine how these drugs influence the B cell compartment in
      patients with JIA. METHODS: B cell subpopulations and follicular helper T (Tfh)
      cells in the peripheral blood of JIA patients were investigated by multicolor
      flow cytometry. Serum immunoglobulin and BAFF levels were determined by enzyme
      linked immunosorbent assay. RESULTS: There was a significant decrease in
      transitional B cells and significantly lower serum immunoglobulin levels in
      patients receiving MTX than in untreated patients and those receiving etanercept.
      In contrast, etanercept treatment had no effect on most of the B cell
      subpopulations, but resulted in significantly lower BAFF levels and increased
      numbers of Tfh cells. Thus, our findings indicate an unexpected and previously
      unknown direct effect of low-dose MTX on B cells, whereas etanercept had a more
      indirect influence. CONCLUSION: Our results contribute to a better understanding
      of the potency of MTX in autoantibody-mediated autoimmune disease and present a
      possible mechanism of prevention of the development of drug-induced antibodies to
      biologic agents. The finding that MTX and etanercept affect the B cell
      compartment differently supports the notion that combination therapy with
      etanercept and MTX is more effective than monotherapy.

PMID- 24909569
TI  - Description of urolithin production capacity from ellagic acid of two human
      intestinal Gordonibacter species.
AB  - Ellagitannin and ellagic acid metabolism to urolithins in the gut shows a large
      human interindividual variability and this has been associated with differences
      in the colon microbiota. In the present study we describe the isolation of one
      urolithin-producing strain from the human faeces of a healthy volunteer and the
      ellagic acid transformation to different urolithin metabolites by two species of
      intestinal bacteria. The isolate belongs to a new species described as
      Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter
      genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce
      urolithins. Both human intestinal bacteria grew similarly in the presence and
      absence of ellagic acid at 30 MUM concentration. Ellagic acid catabolism and
      urolithin formation occurred during the stationary phase of the growth of the
      bacteria under anaerobic conditions. The HPLC-MS analyses showed the sequential
      production of pentahydroxy-urolithin (urolithin M-5), tetrahydroxy-urolithin
      (urolithin M-6) and trihydroxy-urolithin (urolithin C), while dihydroxy
      urolithins (urolithin A and isourolithin A), and monohydroxy-urolithin (urolithin
      B) were not produced in pure cultures. Consequently, either other bacteria from
      the gut or the physiological conditions found in vivo are necessary for
      completing metabolism until the final urolithins (dihydroxy and monohydroxy
      urolithins) are produced. This is the first time that the urolithin production
      capacity of pure strains has been demonstrated. The identification of the
      urolithin-producing bacteria is a relevant outcome as urolithin implication in
      health (cardiovascular protection, anti-inflammatory and anticarcinogenic
      properties) has been supported by different bioassays and urolithins can be used
      in the development of functional foods and nutraceuticals. This study represents
      an initial work that opens interesting possibilities of describing enzymatic
      activities involved in urolithin production that can help in understanding both
      the human interindividual differences in polyphenol metabolism, the microbial
      pathways involved, and the role of polyphenols in human health. The presence of
      urolithin producing bacteria can indirectly affect the health benefits of
      ellagitannin consumption. 

PMID- 24909568
TI  - IFIT1: A dual sensor and effector molecule that detects non-2'-O methylated viral
      RNA and inhibits its translation.
AB  - Our understanding of the antiviral actions of IFIT1, one of the most strongly
      induced interferon stimulated genes (ISGs), has advanced remarkably within the
      last few years. This review focuses on the recent cellular, biochemical, and
      structural discoveries that have provided new insight as to how IFIT1 functions
      as both a sensor and effector molecule of the cellular innate immune system.
      IFIT1 can detect viral RNA lacking 2'-O methylation on their cap structures or
      displaying a 5'-triphosphate moiety and inhibit their translation or sequester
      them from active replication. Because of these inhibitory actions, many viruses
      have evolved unique mechanisms to evade IFIT1 to facilitate replication, spread
      of infection, and disease pathogenesis.

PMID- 24909572
TI  - Engineering the specificity of trehalose phosphorylase as a general strategy for
      the production of glycosyl phosphates.
AB  - A two-step process is reported for the anomeric phosphorylation of galactose,
      using trehalose phosphorylase as biocatalyst. The monosaccharide enters this
      process as acceptor but can subsequently be released from the donor side, thanks
      to the non-reducing nature of the disaccharide intermediate. A key development
      was the creation of an optimized enzyme variant that displays a strict
      specificity (99%) for beta-galactose 1-phosphate as product. 

PMID- 24909571
TI  - Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody:
      epitope definition and implications in risk stratification of patients under
      natalizumab therapy.
AB  - JC virus (JCPyV) has gained novel clinical importance as cause of progressive
      multifocal leukoencephalopathy (PML), a rare demyelinating disease recently
      associated to immunomodulatory drugs, such as natalizumab used in multiple
      sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and
      this makes the need of PML risk stratification among natalizumab-treated patients
      very compelling. Clinical and laboratory-based risk-stratification markers have
      been proposed, one of these is represented by the JCPyV-seropositive status,
      which includes about 54% of MS patients. We recently proposed to investigate the
      possible protective role of neutralizing humoral immune response in preventing
      JCPyV reactivation. In this proof-of-concept study, by cloning the first human
      monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1,
      we optimized a robust anti-JCPyV neutralization assay. This allowed us to
      evaluate the neutralizing activity in JCPyV-positive sera from MS patients,
      demonstrating the lack of correlation between the level of anti-JCPyV antibody
      and anti-JCPyV neutralizing activity. Relevant consequences may derive from
      future clinical studies induced by these findings; indeed the study of the serum
      anti-JCPyV neutralizing activity could allow not only a better risk
      stratification of the patients during natalizumab treatment, but also a better
      understanding of the pathophysiological mechanisms leading to PML, highlighting
      the contribution of peripheral versus central nervous system JCPyV reactivation.
      Noteworthy, the availability of GRE1 could allow the design of novel
      immunoprophylactic strategies during the immunomodulatory treatment. 

PMID- 24909570
TI  - In vitro and in vivo evaluation of two carrageenan-based formulations to prevent
      HPV acquisition.
AB  - Commercial vaccines against human papillomavirus (HPV) have low uptake due to
      parental autonomy, dosing regimen, cost, and cold chain storage requirements.
      Carrageenan (CG)-based formulations prevent HPV infection in vitro and in vivo
      but data are needed on the durability of anti-HPV activity and the effect of
      seminal plasma (SP). The Population Council's PC-515 gel and the lubricant Divine
      9 were tested for their physicochemical properties and anti-HPV activity against
      HPV16, 18, and 45 pseudoviruses (PsVs). Anti-PsV activity was estimated using the
      luciferase assay in HeLa cells and the HPV PsV luciferase mouse model.
      Formulations were applied intravaginally either 2h pre/2h post (-2h/+2h) or 24h
      pre (-24h) relative to challenge with HPV16 or 45 PsV in PBS or SP/PBS. Both
      formulations showed broad-spectrum anti-HPV activity in vitro (IC50: 1-20ng/ml),
      significantly decreasing HPV PsV infection in the mouse model (-2h/+2h,
      p<0.0001). PC-515 protected better than Divine 9 in the -24h dosing regimen
      (p<0.0001) and comparable to Divine 9 in the -2h/+2h regimen (p=0.9841). PC-515
      retained full activity in the murine model when PsV solutions contained human SP.
      The durable, potential broad-spectrum anti-HPV activity of CG formulations in the
      presence of SP supports their further development to prevent HPV acquisition. 

PMID- 24909573
TI  - Prevalence of pre-existing risk factors for adverse events associated with
      atypical antipsychotics among commercially insured and medicaid insured patients
      newly initiating atypical antipsychotics.
AB  - BACKGROUND: Atypical antipsychotics (AA) differ from one another in their adverse
      event (AE) profiles. Patient-specific pre-existing risk factors for AEs,
      including comorbidities and concomitant medications, may render the use of
      certain AAs potentially inappropriate, and others relatively safer or more
      tolerable. OBJECTIVE: To quantify the prevalence of pre-existing risk factors for
      AEs and potential drug-drug interactions (DDIs) associated with AA treatment
      among patients with schizophrenia (SCZ), bipolar disorder (BD), or major
      depressive disorder (MDD) newly-initiating AA treatment. METHODS: Retrospective,
      observational study using US claims databases. Patients identified had newly
      initiated on a single AA (1/1/2010-11/30/2011; index date), were aged 18-64
      years, had insurance enrolment for 12 months pre- (baseline) and 1 month post
      index, and had >=1 medical claim with an ICD-9-CM diagnosis of SCZ, BD, or MDD
      during baseline. A comprehensive list of AE risk factors, including potential
      DDIs, was developed based on AA package inserts. Administrative claims-based
      identification algorithms flagged the presence of each medical risk factor during
      baseline and identified concomitant prescribing of medications (90 days pre- to
      30 days post-index) potentially causing DDIs with AAs. RESULTS: Of 97,010
      patients identified, mean age was 41.2 years and 66.7% were female. Among
      patients initiating AA treatment, prevalence of pre-existing AE risk factors were
      aripiprazole 32.2%; olanzapine 51.6%; ziprasidone 75.6%; quetiapine 77.4%;
      risperidone 82.5%. CONCLUSION: Despite the availability of several AAs to treat
      psychiatric conditions, pre-existing AE risk factors can limit patient treatment
      options. Given inter-AA variability in risk factors, open access to AA may help
      to optimize appropriate prescribing.

PMID- 24909574
TI  - Adverse drug reactions amongst adult patients admitted in Lagos State University
      Teaching Hospital Lagos, Nigeria.
AB  - BACKGROUND: Adverse drug reaction (ADR) is a global drug therapy problem. It has
      been rated as one of the top leading causes of morbidity and mortality. In
      Nigeria, not much is known about ADRs especially with the existing weak post
      marketing surveillance for monitoring drug use, and its effect on the population.
      OBJECTIVES: The study is aimed at determining the incidence of ADRs,
      presentations of ADRs, classes of drugs that frequently cause ADRs and predictors
      of ADRs in adult medical in-patients in LASUTH. METHOD: A retrospective study of
      six hundred and twenty four (624) case notes of all patients admitted to the
      medical wards in LASUTH between January 1, 2009 and December 31, 2009 was carried
      out. Information obtained included age, gender, and adverse drug reaction and
      drug details. The results obtained were analyzed using SPSS version 16
      statistical software. Level of significance was set at p <= 0.05. RESULTS: A
      total of 624 case notes consisting of 358 males and 266 females were assessed.
      The number of patients who experienced adverse drug reactions was 67 (n = 624,
      10.7%). The incidence rate of ADRs in LASUTH from the study was 10.7 per 100
      patients' population. Most of the ADRs observed were type A reactions (97.8%).
      Mostly implicated classes of drugs were antidiabetics (26.7%) and NSAIDs (29.3%).
      CONCLUSION: The incidence rate of ADRs was 10.7%. ADRs which are predictable and
      preventable occur in hospitalized patients, such may be prevented or minimized by
      implementing measures to target specific drugs that are commonly suspected.

PMID- 24909575
TI  - Triptan-induced torsades de pointes and ventricular fibrillation cardiac arrest:
      case report and review of the literature.
AB  - Migraine is a potentially debilitating neurologic disorder affecting
      approximately 12% of the United States population. Sumatriptan manufacturer
      provided drug information states that life threatening arrhythmias, including
      ventricular tachycardia and ventricular fibrillation (VF), have been reported. A
      literature search revealed only seven reported cases of ventricular arrhythmias
      immediately after sumatriptan administration. Twenty minutes after a 42 year old
      female received sumatriptan, her femoral pulses were not palpable and the
      electrocardiograph (EKG) showed torsades de pointes followed by VF. After
      defibrillation and one round of cardiopulmonary resuscitation (CPR), the patient
      regained spontaneous circulation. The patient was eventually discharged home.
      Despite studies concluding that sumatriptan has minimal effects on coronary
      arteries, several cases of sumatriptan-associated myocardial infarction have been
      documented. In addition, a small number of documented cases have reported life
      threatening arrhythmias and cardiorespiratory arrest after sumatriptan
      administration. 

PMID- 24909576
TI  - Middle-of-the-night administration of sleep medication: a critical review of the
      effects on next morning driving ability.
AB  - STUDY OBJECTIVES: Sleep maintenance problems are common, hence treatments
      enabling patients to fall asleep more rapidly after middle-of-the-night (MOTN)
      awakenings, without impairing next morning alertness, are needed. This literature
      review compares the effects of MOTN administration of various hypnotics on
      morning driving ability, a potentially dangerous daily activity under conditions
      of impairment. METHODS: A literature search was conducted identifying on-the-road
      driving studies examining the effects of MOTN administration of hypnotics on
      morning driving performance. In a standardized 100-km highway driving test in
      normal traffic, subjects were instructed to drive with a steady lateral position
      and constant speed of 95 km/h. The primary outcome measure of the driving test is
      the Standard Deviation of Lateral Position (SDLP, cm), i.e. weaving of the car.
      RESULTS: Four driving studies were identified. Driving performance after MOTN
      administration of traditional benzodiazepine hypnotics was not examined. Zolpidem
      (10 mg and 20 mg, oral immediate release tablets) significantly impaired driving
      in a dose-dependent manner, when tested 4 hours after MOTN administration. Also,
      gaboxadol (15 mg) and zopiclone (7.5 mg) significantly impaired next-morning
      driving after MOTN administration. In contrast, sublingual zolpidem (3.5 mg) and
      zaleplon (10 mg and 20 mg) did not significantly affect driving 4 hours after
      MOTN administration. CONCLUSION: Driving was not affected 4 hours after MOTN
      administration of sublingual zolpidem (3.5 mg) or zaleplon (10 mg and 20 mg).
      Significant driving impairment was found after MOTN administration of zolpidem
      (10 and 20 mg), gaboxadol (15 mg), and zopiclone (7.5 mg).

PMID- 24909577
TI  - A descriptive analysis of post-chemotherapy development of interstitial lung
      disease using spontaneous reporting data in Japan.
AB  - This descriptive study used the Japanese spontaneous reporting data to
      investigate the time taken (TTILD) to development of interstitial lung disease
      (ILD) after initiation of chemotherapy and the death rates attributed in part to
      post-chemotherapy ILD (i.e., DR) for anticancer drugs. We evaluated TTILD and DR
      endpoints for 36 anticancer drugs, which are widely used for treating 11 solid
      and 3 hematological cancers, and are suspected of causing ILD, by using 8- year
      spontaneous reporting data recording for 2,553 patients in the reporting system
      of the relevant Japanese regulatory agency. The median TTILD and overall DR
      attributable to post-chemotherapy ILD for the drugs were 1.8 months and 29%,
      respectively. For most drugs, the median TTILDs were between 1 to 4 months, and
      the DRs attributable to postchemotherapy ILD were <40%; however, TTILDs were as
      long as 4 to 6 months and DRs attributable to postchemotherapy ILD were >=40% for
      several other drugs. Of the 36 drugs, we identified those that may trigger
      postchemotherapy late-onset ILDs or result in high DRs. The anticancer drugs that
      may have triggered late-onset ILDs were defined as those that caused ILD
      development after approximately 4 months from the initial drug administration. 

PMID- 24909578
TI  - Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of
      malaria in pregnancy, Mansa, Zambia.
AB  - BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with
      sulphadoxine-pyrimethamine (SP) decreases adverse effects of malaria during
      pregnancy. Zambia implemented its IPTp-SP programme in 2003. Emergence of SP
      resistant Plasmodium falciparum threatens this strategy. The quintuple mutant
      haplotype (substitutions in N51I, C59R, S108N in dhfr and A437G and K540E in dhps
      genes), is associated with SP treatment failure in non-pregnant patients with
      malaria. This study examined efficacy of IPTp-SP and presence of the quintuple
      mutant among pregnant women in Mansa, Zambia. METHODS: In Mansa, an area with
      high malaria transmission, HIV-negative pregnant women presenting to two
      antenatal clinics for the 1st dose of IPTp-SP with asymptomatic parasitaemia were
      enrolled and microscopy for parasitaemia was done weekly for five weeks. Outcomes
      were parasitological failure and adequate parasitological response (no
      parasitaemia during follow-up). Polymerase chain reaction assays were employed to
      distinguish recrudescence from reinfection, and identify molecular markers of SP
      resistance. Survival analysis included those who had reinfection and incomplete
      follow-up (missed at least one follow-up). RESULTS: Of the 109 women included in
      the study, 58 (53%) completed all follow-up, 34 (31%) had incomplete follow-up,
      and 17 (16%) were lost to follow-up after day 0. Of those who had complete follow
      up, 15 (26%, 95% confidence interval [CI] [16-38]) had parasitological failure.
      For the 92 women included in the survival analysis, median age was 20 years
      (interquartile range [IQR] 18-22), median gestational age was 22 weeks (IQR range
      20-24), and 57% were primigravid. There was no difference in time to failure in
      primigravid versus multigravid women. Of the 84 women with complete haplotype
      data for the aforementioned loci of the dhfr and dhps genes, 53 (63%, 95% CI [50
      70]) had quintuple mutants (two with an additional mutation in A581G of dhps).
      Among women with complete follow-up and quintuple mutants, 22% had
      parasitological failure versus 0% without (p = 0.44). CONCLUSIONS: While
      underpowered, this study found 26% failure rates of SP given the moderate
      prevalence of the quintuple mutant haplotype. Despite the presence of resistance,
      SP retained some efficacy in clearing parasites in pregnant women, and may remain
      a viable option for IPTp in Zambia.

PMID- 24909580
TI  - The influence of different force and pressure measuring transducers on lower
      extremity kinematics measured during walking.
AB  - The examination of synchronous three dimensional (3-D) kinetics and kinematics of
      walking in laboratory based analyses typically requires participants/patients to
      make foot contact with a force or pressure measuring device. However, it has been
      proposed that this may lead to targeting whereby participants modify their
      natural gait pattern in order to ensure contact with the device. This study aimed
      to determine the extent to which an embedded force plate (EFP) and two different
      pressure mats (PMs) affect natural gait kinematics. Male participants (n = 12,
      age 24.23 SD 4.22 years, height 1.74 m SD 0.10, mass 75.78 SD 6.90 kg) walked at
      a velocity of 1.25 ms(-1) along a 22 m walkway in four different conditions. (1)
      EFP, (2) FootScan (FS) PM, (3) MatScan (MS) PM, (4) no device (ND). 3-D angular
      kinematic parameters were collected using an eight camera motion analysis system.
      Differences in kinematics were examined using repeated measures ANOVAs.
      Significant differences were observed in hip abduction, knee flexion/extension
      and knee abduction between various conditions and may warrant consideration in
      future research. No significant differences were reported at the ankle joint in
      any conditions. Comparing the PMs, no significant differences were observed,
      however, significant differences between the MS and the EFP and ND conditions
      were identified. The research supports the efficacy of collecting gait kinematics
      at the ankle joint and in most variables measured at the knee and hip joints.

PMID- 24909581
TI  - Correlates of dual task cost of standing balance in individuals with multiple
      sclerosis.
AB  - Cognitive and balance dysfunction are common symptoms in individuals with
      multiple sclerosis (MS). Although traditionally seen as separate impairments,
      performing a concurrent cognitive task while maintaining an upright posture
      results in individuals with MS increasing their postural sway (i.e. dual task
      cost (DTC) of balance). However, the factors relating to this phenomenon are not
      clear. This investigation examined the demographic, clinical and cognitive
      correlates of DTC of balance in individuals with MS. Sixty-two persons with MS
      completed both quiet standing and dual task balance trials on a force platform.
      Additionally, they provided demographic information and performed clinical tests
      of balance, spasticity, fall risk and cognitive processing speed. Dual task cost
      was calculated as the percentage change in sway area from the baseline to dual
      task force platform conditions. Overall, there were no significant correlations
      between DTC of balance and any of the outcome measures in the entire sample. In
      contrast, postural sway in the baseline and dual task condition were found to
      correlate with disability, fall risk, balance performance, fatigue, cognitive
      processing speed and age. Secondary analysis revealed different correlates of DTC
      of balance in those with low versus high baseline sway. The results suggest that
      the change in standing balance with the simultaneous performance of cognitive
      task may only be informative in individuals with minimal balance dysfunction. 

PMID- 24909579
TI  - Agreement between fiber optic and optoelectronic systems for quantifying sagittal
      plane spinal curvature in sitting.
AB  - Spinal posture affects how individuals function from a manual wheelchair. There
      is a need to directly quantify spinal posture in this population to ultimately
      improve function. A fiber optic system, comprised of an attached series of
      sensors, is promising for measuring large regions of the spine in individuals
      sitting in a wheelchair. The purpose of this study was to determine the agreement
      between fiber optic and optoelectronic systems for measuring spinal curvature,
      and describe the range of sagittal plane spinal curvatures in natural sitting.
      Able-bodied adults (n = 26, 13 male) participated. Each participant assumed three
      sitting postures: natural, slouched (accentuated kyphosis), and extension
      (accentuated lordosis) sitting. Fiber optic (ShapeTape) and optoelectronic
      (Optotrak) systems were applied to the skin over spinous processes from S1 to C7
      and used to measure sagittal plane spinal curvature. Regions of kyphosis and
      lordosis were identified. A Cobb angle-like method was used to quantify lordosis
      and kyphosis. Generalized linear model and Bland-Altman analyses were used to
      assess agreement. A strong correlation exists between curvature values obtained
      with Optotrak and ShapeTape (R(2) = 0.98). The mean difference between Optotrak
      and ShapeTape for kyphosis in natural, extension, and slouched postures was 4.30
      degrees  (95% LOA: -3.43 to 12.04 degrees ), 3.64 degrees  (95% LOA: -1.07 to
      8.36 degrees ), and 4.02 degrees  (95% LOA: -2.80 to 10.84 degrees ),
      respectively. The mean difference for lordosis, when present, in natural and
      extension postures was 2.86 degrees  (95% LOA: -1.18 to 6.90 degrees ) and 2.55
      degrees  (95% LOA: -3.38 to 8.48 degrees ), respectively. In natural sitting, the
      mean +/- SD of kyphosis values was 35.07 +/- 6.75 degrees . Lordosis was detected
      in 8/26 participants: 11.72 +/- 7.32 degrees . The fiber optic and optoelectronic
      systems demonstrate acceptable agreement for measuring sagittal plane
      thoracolumbar spinal curvature.

PMID- 24909582
TI  - Structural rheology of focal conic domains: a stress-quench experiment.
AB  - We study the dynamics of focal conic domain (FCD) formation in a thermotropic
      smectic phase under shear stress. It is known that increasing the shear stress
      induces a non-equilibrium phase transition from a smectic phase with FCDs (SmAI)
      to another smectic phase (SmAII) in which the layers are oriented. By quenching
      the shear stress from the SmAII phase to the SmAI phase, we find three
      characteristic modes in the FCD formation process. The first mode is attributed
      to the edge dislocation dynamics induced by climb motions. The second mode
      results from FCD formation. The first and second modes show slowing down close to
      the smectic-nematic transition temperature, implying that the dynamics are
      dominated by dislocation unbinding. The third mode originates from the alignment
      of FCDs which form oily streaks. Such an alignment occurs when the shear stress
      balances the line tension of the oily streaks. 

PMID- 24909583
TI  - Instrumental assessment of velopharyngeal function and resonance: a review.
AB  - The purpose of this literature review is to describe and discuss instrumental
      assessment techniques of the velopharyngeal function in order to diagnose
      velopharyngeal disorders and resonance characteristics. Both direct and indirect
      assessment techniques are addressed, in which successively nasopharyngoscopy,
      videofluoroscopy, magnetic resonance imaging (MRI), cephalometric radiographic
      analysis, computed tomography (CT), ultrasound, acoustic and aerodynamic
      measurements are considered. Despite the multiple instrumental assessments
      available to detect and define velopharyngeal dysfunction, the ideal technique is
      not yet accessible. Therefore, a combination of different quantitative parameters
      can possibly form a solution for a more reliable determination of resonance
      disorders. These multi-dimensional approaches will be described and discussed.
      The combination of quantitative measurement techniques and perceptual evaluation
      of nasality will probably remain necessary to provide sufficient information to
      make appropriate decisions concerning the diagnosis and treatment of resonance
      disorders. LEARNING OUTCOMES: The reader will be able to describe and discuss
      currently available instrumental techniques to assess the velopharyngeal
      mechanism and its functioning in order to diagnose velopharyngeal disorders.
      Additionally, he will be able to explain the possible advantages of the
      combination of several types of complementary measurement techniques.

PMID- 24909585
TI  - Vitamin K deficiency evaluated by serum levels of undercarboxylated osteocalcin
      in patients with anorexia nervosa with bone loss.
AB  - BACKGROUND & AIMS: Osteoporosis is a chief complication in patients with anorexia
      nervosa. Serum levels of undercarboxylated osteocalcin reflect serum and bone
      vitamin K deficiency. We investigated vitamin K status in patients with anorexia
      nervosa to help establish prevention and treatment recommendations for
      osteoporosis. METHODS: Fifty-four female amenorrheic patients with anorexia
      nervosa (29 restricting-type and 25 binge eating/purging type) (age, 28.0 (26.7
      31.1) (mean (95% CI)) years; body mass index, 14.8 (14.1-15.5) kg/m(2), duration
      of illness; 107.3 (88.5-126.0) months) and 15 age-matched healthy females were
      included in this study. We measured serum levels of undercarboxylated
      osteocalcin, biochemical and nutritional markers, and bone metabolic markers.
      Dietary vitamin K intake was evaluated by a questionnaire. RESULTS: Lumbar bone
      mineral density and T-scores in patients with anorexia nervosa were 0.756 (0.721
      0.790) g/cm(2) and -2.4 (-2.1 to -2.7), respectively, indicating bone loss. Serum
      levels of undercarboxylated osteocalcin in patients with anorexia nervosa were
      significantly higher than those of controls. The 17% of restricting type and 40%
      of binge eating/purging type anorexia nervosa patients, serum levels of
      undercarboxylated osteocalcin were higher than 4.5 ng/ml and were diagnosed with
      vitamin K deficiency. Serum levels of undercarboxylated osteocalcin correlated
      significantly and negatively with vitamin K intake in patients with anorexia
      nervosa. CONCLUSIONS: Patients with anorexia nervosa had vitamin K deficiency.
      Since a supplement of vitamin K might be effective for maintaining bone quality,
      we provide recommendations regarding vitamin K intake for prevention and
      treatment of osteoporosis in patients with AN.

PMID- 24909584
TI  - Extra-nigral pathological conditions are common in Parkinson's disease with
      freezing of gait: an in vivo positron emission tomography study.
AB  - Cholinergic denervation has been associated with falls and slower gait speed and
      beta-amyloid deposition with greater severity of axial motor impairments in
      Parkinson disease (PD). However, little is known about the association between
      the presence of extra-nigral pathological conditions and freezing of gait (FoG).
      Patients with PD (n = 143; age, 65.5 +/- 7.4 years, Hoehn and Yahr stage, 2.4 +/-
      0.6; Montreal Cognitive Assessment score, 25.9 +/- 2.6) underwent [(11) C]methyl
      4-piperidinyl propionate acetylcholinesterase and [(11) C]dihydrotetrabenazine
      dopaminergic PET imaging, and clinical, including FoG, assessment in the
      dopaminergic "off" state. A subset of subjects (n = 61) underwent [(11)
      C]Pittsburgh compound-B beta-amyloid positron emission tomography (PET) imaging.
      Normative data were used to dichotomize abnormal beta-amyloid uptake or
      cholinergic deficits. Freezing of gait was present in 20 patients (14.0%).
      Freezers had longer duration of disease (P = 0.009), more severe motor disease (P
      < 0.0001), and lower striatal dopaminergic activity (P = 0.013) compared with non
      freezers. Freezing of gait was more common in patients with diminished
      neocortical cholinergic innervation (23.9%, chi(2)  = 5.56, P = 0.018), but not
      in the thalamic cholinergic denervation group (17.4%, chi(2)  = 0.26, P = 0.61).
      Subgroup analysis showed higher frequency of FoG with increased neocortical beta
      amyloid deposition (30.4%, Fisher Exact test: P = 0.032). Frequency of FoG was
      lowest with absence of both pathological conditions (4.8%), intermediate in
      subjects with single extra-nigral pathological condition (14.3%), and highest
      with combined neocortical cholinopathy and amyloidopathy (41.7%; Cochran-Armitage
      trend test, Z = 2.63, P = 0.015). Within the group of freezers, 90% had at least
      one of the two extra-nigral pathological conditions studied. Extra-nigral
      pathological conditions, in particular the combined presence of cortical
      cholinopathy and amyloidopathy, are common in PD with FoG and may contribute to
      its pathophysiology. (c) 2014 International Parkinson and Movement Disorder
      Society. 

PMID- 24909586
TI  - Comparison of physical activity using questionnaires (leisure time physical
      activity instrument and physical activity at home and work instrument) and
      accelerometry in fibromyalgia patients: the Al-Andalus project.
AB  - OBJECTIVE: To compare the levels of physical activity (PA) assessed with
      questionnaires (Leisure Time Physical Activity Instrument [LTPAI], Physical
      Activity at Home and Work Instrument [PAHWI]) and accelerometry in patients with
      fibromyalgia; and to analyze the test-retest reliability of these questionnaires.
      DESIGN: Cross-sectional study. SETTING: Local fibromyalgia association.
      PARTICIPANTS: Participants (N=99; 5 men) with fibromyalgia with a mean age of
      50.2+/-9.5 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Participants carried an accelerometer for 1 week and completed the LTPAI and
      PAHWI twice (separated by a 1-wk interval). The LTPAI and PAHWI were summed to
      obtain overall values of PA. RESULTS: Time spent in total, moderate, and moderate
      vigorous PA was higher (P<.01) when assessed by the LTPAI and PAHWI compared with
      accelerometry. The Bland-Altman method showed an absence of agreement between the
      LTPAI and PAHWI and the accelerometer for moderate, moderate-vigorous, and total
      PA. The test-retest reliability for the workplace subscale and total score of the
      PAHWI showed high and moderate intraclass correlation coefficients (ICCs),
      respectively, but also manifested high SE of measurements (up to 179min/d). The
      LTPAI showed low to moderate ICCs and high SE of measurements (up to 79min/d).
      For the LTPAI and PAHWI, the ICCs for total activity across the population were
      low to moderate, and the Bland-Altman method confirmed this lack of agreement.
      CONCLUSIONS: The LTPAI and PAHWI and the accelerometer differ greatly when
      assessing PA. Furthermore, the LTPAI and PAHWI did not show good levels of test
      retest reliability. Therefore, the self-administered LTPAI and PAHWI show
      questionable usefulness to assess PA in populations with fibromyalgia.

PMID- 24909587
TI  - Intraexaminer reliability of hand-held dynamometry in the upper extremity: a
      systematic review.
AB  - OBJECTIVE: To summarize and appraise the literature on the intraexaminer
      reliability of hand-held dynamometry (HHD) in the upper extremity. DATA SOURCES:
      MEDLINE, CINAHL, and EMBASE were searched for relevant studies published up to
      December 2011. In addition, experts were contacted, and journals and reference
      lists were hand searched. STUDY SELECTION: To be included in the review, articles
      needed to (1) use a repeated-measures, within-examiner(s) design; (2) include
      symptomatic or asymptomatic individuals, or both; (3) use HHD to measure muscle
      strength in any of the joints of the shoulder, elbow, or wrist with the "make" or
      the "break" technique; (4) report measurements in kilogram, pound, or torque; (5)
      use a device that is placed between the examiner's hand and the subject's body;
      and (6) present estimates of intraexaminer reliability. DATA EXTRACTION: Quality
      assessment and data extraction were performed by 2 reviewers independently. DATA
      SYNTHESIS: Fifty-four studies were included, of which 26 (48%) demonstrated
      acceptable intraexaminer reliability. Seven high-quality studies showed
      acceptable reliability for flexion and extension of the elbow in healthy
      subjects. Conflicting results were found for shoulder external rotation and
      abduction. Reliability for all other movements was unacceptable. Higher estimates
      were reached for within-sessions reliability and if means of trials were used.
      CONCLUSIONS: Intraexaminer reliability of HHD in upper extremity muscle strength
      was acceptable only for elbow measurements in healthy subjects. We provide
      specific recommendations for future research. Physical therapists should not rely
      on HHD measurements for evaluation of treatment effects in patients with upper
      extremity disorders.

PMID- 24909588
TI  - Measuring spasticity and fine motor control (pinch) change in the hand after
      botulinum toxin-A injection using dynamic computerized hand dynamometry.
AB  - OBJECTIVES: To evaluate change in fine motor hand performance and to investigate
      the relationship between existing clinical measures and dynamic computerized
      dynamometry (DCD) after botulinum toxin-A (BTX-A) injections for adults with
      upper limb spasticity. DESIGN: Pretest/posttest clinical intervention study.
      SETTING: Hospital outpatient spasticity clinics. PARTICIPANTS: A convenience
      sample of adults (N=28; mean age, 51y) with upper limb spasticity after acquired
      brain injury. INTERVENTIONS: BTX-A injections for upper limb spasticity
      management. MAIN OUTCOME MEASURES: DCD protocol using a piezoelectric pinch meter
      (termed DCD[pinch]); current clinical upper limb measures: Modified Ashworth
      Scale, Tardieu Scale, Action Research Arm Test, Michigan Hand Outcomes
      Questionnaire, and Goal Attainment Scale. RESULTS: BTX-A produced a significant
      change on DCD(pinch) and some current clinical measures, with correlations
      observed between DCD(pinch) and current clinical measures. CONCLUSIONS:
      DCD(pinch) sensitively and objectively assessed the effects of BTX-A on upper
      limb spasticity during a simulated functionally based pinch and release task.

PMID- 24909589
TI  - Changes in gross motor function and health-related quality of life in adults with
      cerebral palsy: an 8-year follow-up study.
AB  - OBJECTIVE: To describe changes in gross motor function and health-related quality
      of life (HRQOL) in adults with cerebral palsy (CP). DESIGN: An 8-year follow-up
      survey. SETTING: Participants who completed the baseline survey in 2003 were
      invited. PARTICIPANTS: The sample of adults with CP (N=54; response rate=37%)
      included a "younger group" (group 1; n=31; age, 23-27y; 15 women) and an "older
      group" (group 2; n=23; age, 33-42y; 10 women). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The Gross Motor Function Classification System (GMFCS),
      Self-Rated Health (SRH), the Health Utility Index Mark III (HUI3), and the
      Assessment of Quality of Life (AQoL). RESULTS: Eight years after the initial
      survey, 27% of the participants in the combined group had deteriorations on the
      GMFCS, 52% on the SRH, 44% on the HUI3, and 25% on the AQoL. Members of group 1
      reported stable scores as they made the transition to adulthood, while many of
      the group 2 members experienced declines, with relative risk of 1.47 (95%
      confidence interval [CI], 0.16-2.24) on the GMFCS, 1.36 (95% CI, 0.83-2.23) on
      the SRH, 1.19 (95% CI, 0.66-2.15) on the HUI3, and 3.17 (95% CI, 1.12-9.00) on
      the AQoL. CONCLUSIONS: Although much attention has focused on the transitions of
      persons with CP during their late teens and early 20s, this research found that
      deteriorations in the GMFCS levels and the HRQOL were most evident in adults in
      their late 20s and 30s. More detailed longitudinal studies are required to
      evaluate the longer-term health outcomes among persons with CP into their 30s and
      beyond.

PMID- 24909590
TI  - Proper patient selection yields significant and sustained reduction in systolic
      blood pressure following renal artery stenting in patients with uncontrolled
      hypertension: long-term results from the HERCULES trial.
AB  - The Safety and Effectiveness Study of the Herculink Elite Renal Stent to Treat
      Renal Artery Stenosis (HERCULES) trial is a prospective, multicenter trial
      evaluating the safety, effectiveness, and durability of the RX Herculink Elite
      renal stent system (Abbott Vascular, Abbott Park, IL) in select patients with
      atherosclerotic renal artery stenosis and uncontrolled hypertension. A total of
      202 patients were enrolled between August 2007 and October 2009. The primary
      endpoint, 9-month binary restenosis, was 10.5% determined by core laboratory
      adjudicated duplex ultrasound and/or angiography. Additional analyses included
      changes in blood pressure, antihypertensive medications, renal function (RF),
      major adverse events (MAEs) (death, ipsilateral nephrectomy, and embolic events
      resulting in kidney damage), and clinically driven target lesion
      revascularization (CD-TLR) between baseline and 36 months. Freedom from MAE was
      98.5% at 30 days. At 36 months, freedom from death, nephrectomy, and CD-TLR were
      90.1%, 100%, and 91.8%, respectively. After 30 days there were no site-reported
      embolic events resulting in kidney damage. The mean baseline systolic blood
      pressure of 162+/-18 mm Hg significantly decreased postprocedure and through 36
      months (mean systolic blood pressure 141 mm Hg [P<.0001] and 146 mm Hg [P<.0001],
      respectively). No differences were noted in antihypertensive medications or RF
      compared with baseline. The HERCULES trial demonstrated sustained clinically and
      statistically significant reduction in SBP in patients with uncontrolled HTN.
      Coupled with the low core laboratory-adjudicated in-stent restenosis, acceptable
      procedural complication rates (1.5%), and <10% CD-TLR, the study suggests that
      there may be a role for renal artery stenting using contemporary stent
      technology. 

PMID- 24909591
TI  - The concept of human dignity in the ethics of genetic research.
AB  - Despite criticism that dignity is a vague and slippery concept, a number of
      international guidelines on bioethics have cautioned against research that is
      contrary to human dignity, with reference specifically to genetic technology.
      What is the connection between genetic research and human dignity? In this
      article, I investigate the concept of human dignity in its various historical
      forms, and examine its status as a moral concept. Unlike Kant's ideal concept of
      human dignity, the empirical or relational concept takes human dignity as
      something that is affected by one's circumstances and what others do. I argue
      that the dignity objection to some forms of genetic research rests on a view of
      human nature that gives humans a special status in nature - one that is
      threatened by the potential of genetic research to reduce individuals to their
      genetic endowment. I distinguish two main philosophical accounts of human nature.
      One of these, the Aristotelian view, is compatible with the use of genetic
      technology to help humans realize their inherent potential to a fuller extent. 

PMID- 24909592
TI  - Ambient noise impact on accuracy of automated hearing assessment.
AB  - OBJECTIVE: The aim of this study was to determine the effect of ambient noise on
      the accuracy of thresholds obtained using the KUDUwave portable clinical
      audiometer as compared to those obtained using a GSI-61 clinical audiometer in a
      sound booth. DESIGN: Pure-tone air conduction thresholds were obtained in three
      conditions: (1) with a clinical audiometer in a quiet sound booth, (2) with the
      KUDUwave in a quiet sound booth, and (3) with the KUDUwave with 40 dBA of
      background noise. STUDY SAMPLE: A total of 31 individuals ranging in age from 15
      to 80 years participated in the study, 21 with normal hearing and ten with
      hearing loss. RESULTS: Eighty-nine percent of thresholds obtained with the
      KUDUwave in quiet, and 92% of thresholds obtained with the KUDUwave in background
      noise were within 5 dB of those obtained with the clinical audiometer. Accuracy
      was poorer at 250 Hz and 8000 Hz. CONCLUSION: Ambient noise typical of that found
      in a non-sound-treated room, did not affect the accuracy of air conduction
      hearing thresholds obtained with the KUDUwave. The KUDUwave may be a viable
      method of testing when a clinical audiometer and sound booth are not available.

PMID- 24909593
TI  - Repeatability, agreement, and feasibility of using the threshold equalizing noise
      test and fast psychophysical tuning curves in a clinical setting.
AB  - OBJECTIVE: To investigate repeatability, agreement, and clinical feasibility of
      the threshold equalizing noise (TEN) test and fast psychophysical tuning curve
      (PTC) measurements to detect off-frequency listening, an indicator of cochlear
      dead regions (DRs). DESIGN: The TEN-test was carried out from 0.5 to 4 kHz and
      fast PTCs were carried out at >= 2 frequencies. STUDY SAMPLE: The TEN-test was
      completed on 70 ears; fast PTCs were measured on 20 ears. RESULTS: TEN-test
      findings were repeatable in terms of meeting the criteria for a DR (97%) and
      identifying the same edge frequency (fe) (87%). In all cases, fast PTCs were
      repeatable in terms of meeting the criteria for DRs. There was 87% agreement
      between the two procedures in terms of the presence of off-frequency listening,
      and there was 73% agreement in terms of fe. Fast PTCs had a 10% lower 'conclusive
      finding' rate than the TEN-test and the test duration was typically 40 minutes
      longer. CONCLUSIONS: Both the TEN-test and fast PTCs have high test-retest
      repeatability. The TEN-test is more clinically feasible due to its shorter test
      duration and higher interpretation rate, but it may underestimate the extent of a
      DR because of its inability to precisely identify fe.

PMID- 24909594
TI  - Cavitand-grafted silicon microcantilevers as a universal probe for illicit and
      designer drugs in water.
AB  - The direct, clean, and unbiased transduction of molecular recognition into a
      readable and reproducible response is the biggest challenge associated to the use
      of synthetic receptors in sensing. All possible solutions demand the mastering of
      molecular recognition at the solid-liquid interface as prerequisite. The socially
      relevant issue of screening amine-based illicit and designer drugs is addressed
      by nanomechanical recognition at the silicon-water interface. The methylamino
      moieties of different drugs are all first recognized by a single cavitand
      receptor through a synergistic set of weak interactions. The peculiar recognition
      ability of the cavitand is then transferred with high fidelity and robustness on
      silicon microcantilevers and harnessed to realize a nanomechanical device for
      label-free detection of these drugs in water. 

PMID- 24909595
TI  - How might we increase success in marine-based drug discovery?
AB  - Drug discovery from marine organisms has been underway for > 60 years and there
      have been notable successes in discovering, developing and introducing clinical
      agents derived from marine sources. Such examples include: the analgesic
      ziconotide and the anti cancer compound trabectedin. However, in light of the
      pressing need for new drugs, particularly those with anti-infective and
      anticancer properties, there is strong justification for increased exploration of
      marine organisms as sources of novel compounds. This article considers approaches
      that might enhance our chances of delivering new medicines from marine-based drug
      discovery efforts. Consideration is given to the organisms and habitats deserving
      of more attention and how we might make best use of these marine genetic
      resources. In particular, the opportunities offered by synthetic biology are
      highlighted because these methods allow drug discoverers to explore pathways in
      'non-culturable' species and turn on natural product biosynthesis genes that are
      difficult to activate under laboratory conditions (so-called 'silent' gene
      clusters). 

PMID- 24909596
TI  - A rare case of a chronic syphilitic gumma in a man infected with human
      immunodeficiency virus.
AB  - OBJECTIVE: This paper reports a rare case of a human immunodeficiency virus
      infected man with gummatous syphilis of the face. CASE REPORT: A 39-year-old man
      presented with an ulcer of the face which had been slowly progressive over the
      previous 6 years. Examination showed an ulcerative lesion of the midface
      involving the cheeks, and completely destroying the nose, the upper lip and part
      of the lower lip. The teeth and gums were exposed. The ulcer had a moist,
      purulent base with rolled edges. The patient had human immunodeficiency virus,
      with a cluster of differentiation 4 count of 641 cells per ul. The rapid plasma
      reagin test titre was 1:1024 and the Treponema pallidum haemagglutination assay
      result was positive. Biopsy showed non-necrotising granulomata with a negative
      Warthin-Starry silver stain. There was a dramatic response to treatment with
      penicillin. CONCLUSION: This case study is a reminder that syphilis needs to be
      considered in the differential diagnosis of unusual presentations involving skin
      and bone.

PMID- 24909597
TI  - Focusing and waveguiding of Lamb waves in micro-fabricated piezoelectric phononic
      plates.
AB  - This paper presents results on the numerical and experimental studies of focusing
      and waveguiding of the lowest anti-symmetric Lamb wave in micro-fabricated
      piezoelectric phononic plates. The phononic structure was based on an AT-cut
      quartz plate and consisted of a gradient-index phononic crystal (GRIN PC) lens
      and a linear phononic plate waveguide. The band structures of the square-latticed
      AT-cut quartz phononic crystal plates with different filling ratios were analyzed
      using the finite element method. The design of a GRIN PC plate lens which is
      attached with a linear phononic plate waveguide is proposed. In designing the
      waveguide, propagation modes in square-latticed PC plates with different
      waveguide widths were studied and the results were served for the experimental
      design. In the micro-fabrication, deep reactive ion etching (Deep-RIE) process
      with a laboratory-made etcher was utilized to fabricate both the GRIN PC plate
      lens and the linear phononic waveguide on an 80 MUm thick AT-cut quartz plate.
      Interdigital transducers were fabricated directly on the quartz plate to generate
      the lowest anti-symmetric Lamb waves. A vibro-meter was used to detect the wave
      fields and the measured results on the focusing and waveguiding of the
      piezoelectric GRIN PC lens and waveguide are in good accordance with the
      numerical predictions. The results of this study may serve as a basis for
      developing an active micro plate lens and related devices.

PMID- 24909598
TI  - Ovariectomy in Jenny using subarachnoid propofol administration.
AB  - OBJECTIVE: To evaluate the effects of subarachnoid propofol administration (SPA)
      on analgesia, sedation, ataxia, cardiopulmonary, blood gas variables, and its
      application in ovariectomy in Jennies. STUDY DESIGN: Prospective, randomized,
      clinical trial. ANIMALS: Adult Jennies (n = 20; 100-120 kg; 5-7 years old).
      METHODS: In study 1, 5 Jennies had SPA (n = 5; group 1) through Tuohy catheter,
      and another 5 control Jennies had normal saline subarachnoid administration (n =
      5; group 2). In study 2, 10 Jennies had SPA and ovariectomy (n = 10; group 3). In
      groups 1 and 3 analgesia, sedation and ataxia scores, cardiopulmonary and blood
      gas variables were recorded at different intervals before and after PSA. In group
      2, only cardiopulmonary and blood gas variables were recorded. RESULTS: SPA
      produced pronounced analgesia, mild sedation and minimal ataxia. Heart rate (HR),
      respiratory rate (RR), pulse rate (PR), rectal temperature (RT), arterial blood
      pH, PaO2 , and PaCO2 were not significantly different from base line values after
      subarachnoid administration of either propofol or normal saline. CONCLUSION: SPA
      was found to be useful, efficient and feasible procedure for ovariectomy through
      standing flank laparotomy in Jennies.

PMID- 24909599
TI  - Otorhinolaryngology management of seven patients with iatrogenic penetrating
      injuries from GlideScope(r): our experience.

PMID- 24909600
TI  - KISS1 gene expression in the developing brain of female pigs in pre- and
      peripubertal periods.
AB  - Puberty is associated with an increase in gonadotropin secretion as a result of
      an increase in gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is
      considered to play a key role in puberty onset in many mammalian species,
      including rodents, ruminants and primates. The present study aimed to determine
      if changes in hypothalamic expression of the KISS1 gene, encoding kisspeptin, are
      associated with the onset of puberty in pigs. The animals (n=4 in each group)
      were perfused with 4% paraformaldehyde at 0, 1, 2, 3 and 4 months old, as
      prepubertal stages, and at 5 months old, as the peripubertal stage, following
      each blood sampling. KISS1 gene expressions in coronal sections of brains were
      visualized by in situ hybridization. Plasma luteinizing hormone (LH) was measured
      by radioimmunoassay. KISS1 mRNA signals were observed in the arcuate nucleus
      (ARC) at all ages examined without any significant difference in the number of
      KISS1-expressing cells, indicating that the KISS1 gene is constantly expressed in
      the ARC throughout pubertal development in pigs. The plasma LH concentration was
      the highest in 0-month-old piglets and significantly decreased in the 1- and 2
      month-old groups (P<0.05), suggesting a developing negative feedback mechanism
      affecting gonadotropin release during the prepubertal period. Considering the
      potent stimulating effect of kisspeptin on gonadotropin release in prepubertal
      pigs, kisspeptin secretion rather than kisspeptin synthesis may be responsible
      for the onset of puberty in pigs. 

PMID- 24909601
TI  - Effects of trichostatin A on In vitro development and DNA methylation level of
      the satellite I region of swamp buffalo (Bubalus bubalis) cloned embryos.
AB  - Trichostatin A (TSA), a histone deacetylase inhibitor, has been widely used to
      improve the cloning efficiency in several species. This brings our attention to
      investigation of the effects of TSA on developmental potential of swamp buffalo
      cloned embryos. Swamp buffalo cloned embryos were produced by electrical pulse
      fusion of male swamp buffalo fibroblasts with swamp buffalo enucleated oocytes.
      After fusion, reconstructed oocytes were treated with 0, 25 or 50 nM TSA for 10
      h. The results showed that there was no significant difference in the rates of
      fusion (82-85%), cleavage (79-84%) and development to the 8-cell stage (59-65%)
      among treatment groups. The highest developmental rates to the morula and
      blastocyst stages of embryos were found in the 25 nM TSA-treated group (42.7 and
      30.1%, respectively). We also analyzed the DNA methylation level in the satellite
      I region of donor cells and in in vitro fertilized (IVF) and cloned embryos using
      the bisulfite DNA sequencing method. The results indicated that the DNA
      methylation levels in cloned embryos were significantly higher than those of IVF
      embryos but approximately similar to those of donor cells. Moreover, there was no
      significant difference in the methylation level among TSA-treated and untreated
      cloned embryos. Thus, TSA treatments at 25 nM for 10 h could enhance the in vitro
      developmental potential of swamp buffalo cloned embryos, but no beneficial effect
      on the DNA methylation level was observed. 

PMID- 24909602
TI  - Multimodal white matter imaging to investigate reduced fractional anisotropy and
      its age-related decline in schizophrenia.
AB  - We hypothesized that reduced fractional anisotropy (FA) of water diffusion and
      its elevated aging-related decline in schizophrenia patients may be caused by
      elevated hyperintensive white matter (HWM) lesions, by reduced permeability
      diffusivity index (PDI), or both. We tested this hypothesis in 40/30
      control/patient participants. FA values for the corpus callosum were calculated
      from high angular resolution diffusion tensor imaging (DTI). Whole-brain volume
      of HWM lesions was quantified by 3D-T2w-fluid-attenuated inversion recovery
      (FLAIR) imaging. PDI for corpus callosum was ascertained using multi b-value
      diffusion imaging (15 b-shells with 30 directions per shell). Patients had
      significantly lower corpus callosum FA values, and there was a significant age-by
      diagnosis interaction. Patients also had significantly reduced PDI but no
      difference in HWM volume. PDI and HWM volume were significant predictors of FA
      and captured the diagnosis-related variance. Separately, PDI robustly explained
      FA variance in schizophrenia patients, but not in controls. Conversely, HWM
      volume made equally significant contributions to variability in FA in both
      groups. The diagnosis-by-age effect of FA was explained by a PDI-by-diagnosis
      interaction. Post hoc testing showed a similar trend for PDI of gray mater. Our
      study demonstrated that reduced FA and its accelerated decline with age in
      schizophrenia were explained by pathophysiology indexed by PDI, rather than HWM
      volume. 

PMID- 24909604
TI  - Response to the article "the ideal timing of ureteric stent removal in
      transplantation patients".

PMID- 24909603
TI  - Speech-perception training for older adults with hearing loss impacts word
      recognition and effort.
AB  - The current pupillometry study examined the impact of speech-perception training
      on word recognition and cognitive effort in older adults with hearing loss.
      Trainees identified more words at the follow-up than at the baseline session.
      Training also resulted in an overall larger and faster peaking pupillary
      response, even when controlling for performance and reaction time. Perceptual and
      cognitive capacities affected the peak amplitude of the pupil response across
      participants but did not diminish the impact of training on the other pupil
      metrics. Thus, we demonstrated that pupillometry can be used to characterize
      training-related and individual differences in effort during a challenging
      listening task. Importantly, the results indicate that speech-perception training
      not only affects overall word recognition, but also a physiological metric of
      cognitive effort, which has the potential to be a biomarker of hearing loss
      intervention outcome.

PMID- 24909605
TI  - Thirty-six vaginal constructions: lessons learned.
AB  - OBJECTIVES: The use of bowel for vaginal construction is a well-established
      procedure. In this paper, the lessons learned from 36 vaginoplasties over a 34
      year period are discussed. METHODS: Between 1980 and 2013, 36 patients between 1
      and 21 years of age underwent vaginal construction. In 27 of the 36 patients, an
      inverted V-shaped perineal skin flap was incorporated into the posterior wall of
      the neovagina, and, when required, a detubularized pouch was used to avoid
      traction on the vascular pedicle. In nine patients, the sigmoid colon was
      anastomosed, in a circumferential manner, to the short blind-ending vaginal
      dimple. RESULTS: Two of the nine sigmoid vaginas, where the perineal skin flap
      was omitted, developed introital stenosis. None of the sigmoid neovaginas that
      included the perineal flap developed stenosis. One patient with ileal segment
      vagina, at the onset of puberty, developed introital stenosis after 10 years;
      this was successfully corrected. Nineteen out of 28 patients available for long
      term follow up were sexually active and reported no dyspareunia. CONCLUSIONS:
      Detubularization and reconfiguration to form a pouch reduces the traction on the
      mesentery of the bowel segment, which ensures adequate blood supply to the distal
      entero-cutaneous junction. The inverted V-shaped perineal skin flap should be
      incorporated in the anastomosis to avoid circumferential suture line and
      introital stenosis.

PMID- 24909606
TI  - Ultrasound diagnosis of multicystic dysplastic kidney: is a confirmatory nuclear
      medicine scan necessary?
AB  - OBJECTIVE: It is critical to differentiate between a multicystic dysplastic
      kidney (MCDK) and a kidney with severe hydronephrosis as the treatment varies
      significantly. We designed a study to compare renal ultrasound (RUS) to nuclear
      medicine (NM) scan in the diagnosis of MCDK, in order to determine if RUS can be
      used for the definitive diagnosis of MCKD without use of NM scan. MATERIALS AND
      METHODS: We performed a retrospective review of children with MCDK, who underwent
      both a RUS and Tc-99m MAG3 or DMSA scan. We planned to calculate the positive
      predictive value of an RUS diagnosis of MCDK, using NM scan diagnosis of a
      nonfunctioning kidney as the gold standard. RESULTS: The diagnosis of MCDK was
      made by RUS in 91 patients, 84 of whom had a normal bladder US. NM confirmed the
      diagnosis of MCDK in all 84 of these patients (100%). CONCLUSION: We have
      demonstrated a high predictive value for RUS in the diagnosis of MCDK. Our data
      support that in healthy infants with RUS diagnosis of unilateral MCDK and normal
      bladder US, NM scan may be unnecessary to confirm the diagnosis.

PMID- 24909607
TI  - Scintigraphy evaluation of the types of functional constipation in children with
      bowel bladder dysfunction.
AB  - PURPOSE: To evaluate the types of constipation according to colonic transit time
      in chronically constipated children with dysfunctional voiding (bowel bladder
      dysfunction, BBD group) and to compare the results with transit type in children
      with chronic functional constipation without urinary symptoms (constipation
      group) and children with normal bowel habits, but with lower urinary tract
      symptoms (control group). PATIENTS AND METHODS: One-hundred and one children were
      included and their medical histories were obtained. The BBD group kept a voiding
      diary, and underwent urinalyses and urine culture, ultrasound examination of
      bladder and kidneys and uroflowmetry with pelvic floor electromyography.
      Radionuclear transit scintigraphy was performed in all children according to a
      standardized protocol. Patients were categorized as having either slow-transit
      (ST), functional fecal retention (FFR) or normal transit. RESULTS: FFR was
      diagnosed in 31 out of 38 children with BBD, and 34 out of 43 children in the
      constipation group. ST was found in seven children with BBD, compared with nine
      children in the constipation group. The control group children demonstrated
      normal colonic transit. Urgency, daily urinary incontinence and nocturnal
      enuresis were noted only in children with FFR. Both children with ST constipation
      and FFR complained of difficulties during voiding, voiding postponement and
      urinary tract infections. CONCLUSIONS: FFR is the most common form of
      constipation in children with dysfunctional voiding. However, some children might
      suffer from ST constipation. Differentiation between these two types of
      constipation is clinically significant because they require different treatment.
      Future studies with larger numbers of patients are needed to confirm the noted
      differences in urological symptoms in these two groups of constipated children..

PMID- 24909608
TI  - Bladder muscular wall regeneration with autologous adipose mesenchymal stem cells
      on three-dimensional collagen-based tissue-engineered prepuce and biocompatible
      nanofibrillar scaffold.
AB  - OBJECTIVE: Tissue-engineered prepuce scaffold (TEPS) is a collagen-rich matrix
      with marvelous mechanical properties, promoting in vivo and in vitro tissue
      regeneration. In this study, adipose-derived mesenchymal stem cells (ADMSCs) were
      used to seed TEPS for bladder wall regeneration. Its potential in comparison with
      other materials such as polyglycolic acid (PGA) and nanofibrous scaffolds were
      evaluated. MATERIALS AND METHODS: Rat ADMSCs were cultured and seeded into
      prepared TEPS. A synthetic matrix of electrospun nanofibrous polyamide was also
      prepared. Sprague Dawley rats (n=32) underwent bladder wall regeneration using
      (a) TEPS, (b) TEPS+PGA, (c) TEPS+nanofibrous scaffold, and (d) ADMSC-seeded TEPS,
      between bladder mucosa and seromuscular layer. Animals were followed for 30 and
      90 days post implantation for evaluation of bladder wall regeneration by
      determining CD31/34 and SMC alpha-actin. Cystometric evaluation was also
      performed in all groups and in four separate rats as sham controls 3 months
      postoperatively. RESULTS: Histopathological analysis showed well-organized
      muscular wall generation in ADMSC-seeded TEPS and TEPS+three-dimensional (3D)
      nanofibrous scaffold without significant fibrosis after 90 days, while mild to
      severe fibrosis was detected in groups receiving TEPS and TEPS+PGA.
      Immunohistochemistry staining revealed the maintenance of CD34+, CD31+, and alpha
      SMA in ADMSC-seeded TEPS and TEPS+3D nanofibrous scaffold with significantly
      higher density of CD34+ and CD31+ progenitor cells in ADMSC-seeded TEPS and
      TEPS+3D nanofibrous scaffold, respectively. CONCLUSIONS: This work has crucial
      functional and clinical implications, as it demonstrates the feasibility of ADMSC
      seeded TEPS in enhancing the properties of TEPS in terms of bladder wall
      regeneration.

PMID- 24909609
TI  - Genetic or pharmacologic disruption of the calcineurin-nuclear factor of
      activated T-cells axis prevents social stress-induced voiding dysfunction in a
      murine model.
AB  - OBJECTIVE: Social stress can suppress the voiding reflex, with resultant
      diminished voiding frequency and increased volumes. The calcineurin-NFAT (nuclear
      factor of activated T cells) pathway is important in memory development. It was
      hypothesized that interruption of the calcineurin-NFAT pathway might prevent
      social stress-induced voiding dysfunction. METHODS: Mice were subjected to social
      stress in an established resident-intruder model for 1 h, followed by 23 h of
      barrier separation. NFATc3, NFATc4 knockout (KO) and wild-type (WT) mice were
      studied. At two weeks, voiding patterns were collected; this was followed by
      sacrifice. Corticotropin-releasing factor (CRF) mRNA expression in Barrington's
      nucleus (BN) was determined by in-situ hybridization. RESULTS: Social stress
      decreased voiding frequency and increased voided volumes in WT strains. At
      baseline, NFATc3 KO mice showed decreased voids and increased volumes, while the
      NFATc4 KO mice resisted social stress. However, CRF mRNA increased in WT mice
      following social stress and was increased at baseline in NFATc3 KO mice. It was
      found that CRF mRNA did not increase following social stress in NFATc4 KO mice.
      The administration of CsA to WT mice normalized voiding patterns following social
      stress, albeit with no effect on CRF mRNA in BN. CONCLUSION: Disrupting the
      calcineurin-NFAT axis by either genetic or pharmacologic approaches confers
      resistance to the development of social stress-induced voiding and dysfunction.

PMID- 24909610
TI  - Patient advocate responds to DSD surgery debate.

PMID- 24909611
TI  - Away-from-home eating: nutritional status and dietary intake among Brazilian
      adults.
AB  - OBJECTIVE: To evaluate the association between eating away from home and BMI and
      to examine whether dietary intake differs based on the consumption of away-from
      home food (AFHF). DESIGN: Data were obtained from the first Brazilian National
      Dietary Survey, using food records. The association between the percentage of
      energy provided by foods consumed away from home and BMI status was tested using
      logistic regression models. The mean percentages of energy provided by protein,
      fat, saturated fat and free sugars were calculated based on the consumption of
      foods away from home among AFHF consumers. SETTING: Urban areas of Brazil.
      SUBJECTS: Adults (n 13 736) between 25 and 65 years old. RESULTS: AFHF was not
      associated with BMI status. Individuals who consumed AFHF had higher intakes of
      free sugars away from home than at home and had higher intakes of energy-dense
      foods than AFHF non-consumers. CONCLUSION: Although AFHF consumption was not
      related to overweight or obesity status, individuals who consumed foods away from
      home had higher intakes of energy-dense foods. Public health policies should be
      implemented to help people make healthier food choices away from home.

PMID- 24909612
TI  - Phosphorylation of PrxII promotes JNK-dependent apoptosis in adult cloned pig
      kidney.
AB  - Organ transplantation is the most effective medical therapy for end-stage renal
      disease patients; however, there is a critical shortage of human donor organs.
      Therefore, xenotransplantation using genetically modified cloned porcine kidney
      is considered as a viable solution, but its fundamental therapeutic mechanism and
      difference from non-cloned porcine or human kidney for its clinical application
      is not well known. Here, we performed proteomic analysis to investigate the
      differentially expressed molecules in kidney tissue obtained from cloned porcine
      by SCNT, when compared with normal porcine kidney in same age as a control. A
      total of 80 protein spots were differentially expressed between cloned porcine
      kidney and control kidney, including apoptotic proteins, structural and anti
      oxidant related proteins. Furthermore, very interestingly, the differential
      expression pattern of PrxII in the cloned porcine kidney was distinguishable from
      that in the control kidney in terms of the pI and molecular weight. Along with
      this, apoptotic marker proteins were up-regulated in the cloned porcine kidney.
      We suggested that these alterations were induced by post-translational
      modification such as phosphorylation in PrxII and could be mediated by JNK. With
      this result, we also observed that the down-regulation of JNK activity was caused
      by blockage of phosphorylation in PrxII T89A region. Taken together, cloned
      porcine kidney is more susceptible in JNK-induced apoptosis caused by PrxII
      phosphorylation, in oxidative stress condition. These results will be helpful in
      the application of cloned porcine xeno-transplants for treating end-stage renal
      disease patients in a clinical setting. 

PMID- 24909613
TI  - Combination of MUC1 and MUC4 expression predicts clinical outcome in patients
      with oral squamous cell carcinoma.
AB  - BACKGROUND: Both MUC1 and MUC4 are high molecular weight glycoproteins and are
      independent indicators of worse prognosis in many human epithelial cancers
      including oral squamous cell carcinoma (OSCC). However, there has been no
      investigation of the clinical importance of the co-expression of MUC1 and MUC4 in
      OSCC. The aim of this study was to evaluate the co-expression profile of
      MUC1/MUC4 and analyze the prognostic significance in OSCC. METHODS: We examined
      the expression profile of MUC1 and MUC4 in OSCC tissues from 206 patients using
      immunohistochemistry. The co-expression profile of MUC1/MUC4 and its prognostic
      significance in OSCC was statistically analyzed. RESULTS: MUC1 and MUC4
      overexpression were strongly correlated with each other (p < 0.0001) and a
      combination of both MUC1 and MUC4 expression was a powerful indicator for tumor
      aggressiveness such as tumor size (p = 0.014), lymph node metastasis (0.0001),
      tumor stage (p = 0.006), diffuse invasion (p = 0.028), and vascular invasion (p =
      0.014). The MUC1/MUC4 double-positive patients showed the poorest overall and
      disease-free survival. Multivariate analysis revealed that MUC1/MUC4 double
      positivity was the strong independent prognostic factor for overall and disease
      free survival (p = 0.007 and (p = 0.0019), in addition to regional recurrence (p
      = 0.0025). CONCLUSIONS: Taken together, these observations indicate that the use
      of a combination of MUC1/MUC4 can predict outcomes for patients with OSCC. This
      combination is also a useful marker for predicting regional recurrence. MUC1 and
      MUC4 may be attractive targets for the selection of treatment methods in OSCC.

PMID- 24909614
TI  - Hydrogen sulfide and nitric oxide metabolites in the blood of free-ranging brown
      bears and their potential roles in hibernation.
AB  - During winter hibernation, brown bears (Ursus arctos) lie in dens for half a year
      without eating while their basal metabolism is largely suppressed. To understand
      the underlying mechanisms of metabolic depression in hibernation, we measured
      type and content of blood metabolites of two ubiquitous inhibitors of
      mitochondrial respiration, hydrogen sulfide (H2S) and nitric oxide (NO), in
      winter-hibernating and summer-active free-ranging Scandinavian brown bears. We
      found that levels of sulfide metabolites were overall similar in summer-active
      and hibernating bears but their composition in the plasma differed significantly,
      with a decrease in bound sulfane sulfur in hibernation. High levels of unbound
      free sulfide correlated with high levels of cysteine (Cys) and with low levels of
      bound sulfane sulfur, indicating that during hibernation H2S, in addition to
      being formed enzymatically from the substrate Cys, may also be regenerated from
      its oxidation products, including thiosulfate and polysulfides. In the absence of
      any dietary intake, this shift in the mode of H2S synthesis would help preserve
      free Cys for synthesis of glutathione (GSH), a major antioxidant found at high
      levels in the red blood cells of hibernating bears. In contrast, circulating
      nitrite and erythrocytic S-nitrosation of glyceraldehyde-3-phosphate
      dehydrogenase, taken as markers of NO metabolism, did not change appreciably. Our
      findings reveal that remodeling of H2S metabolism and enhanced intracellular GSH
      levels are hallmarks of the aerobic metabolic suppression of hibernating bears. 

PMID- 24909616
TI  - Similar rate of information transfer on stimulus intensity in accessory and main
      olfactory bulb output neurons.
AB  - Recently, evidence has accumulated that the vomeronasal system cooperates with
      the main olfactory system to process volatile cues that regulate the animal's
      behavior. This is contradictory to the traditional view that the vomeronasal
      system is quite different from the main olfactory system in the time scale of
      information processing. Particularly, the firing rate of mitral/tufted cells in
      the accessory olfactory bulb (MTAOB) is known to be significantly lower than that
      of mitral cells in the main olfactory bulb (MCMOB). To address this question of
      whether the low-frequency firing in MTAOB carries less information than the high
      frequency firing in MCMOB in the early stages of stimulation, we compared MTAOB
      and MCMOB for their firing mechanisms and information transfer characteristics. A
      model computation demonstrated that the inherent channel kinetics of MTAOB was
      responsible for their firing at a lower frequency than MCMOB. Nevertheless, our
      analysis suggested that MTAOB were comparable to MCMOB in both the amount and
      speed of information transfer about depolarizing current intensity immediately
      after current injection onset (<200ms). Our results support a hypothesis of
      simultaneous processing of common cues in both systems. 

PMID- 24909615
TI  - Inducible nitric oxide synthase mediates MG132 lethality in leukemic cells
      through mitochondrial depolarization.
AB  - Proteasomes are highly expressed in rapidly growing neoplastic cells and
      essential for controlling the cell cycle process and mitochondrial homeostasis.
      Pharmacological inhibition of the proteasome shows a significant anticancer
      effect on hematopoietic malignancies that is usually associated with the
      generation of reactive oxygen species. In this study, we comprehensively
      investigated the role of endogenous oxidants in various cellular events of K562
      leukemic cells in response to treatment with MG132, a proteasome inhibitor. MG132
      at 1.4 uM potently triggered G2/M arrest, mitochondrial depolarization, and
      apoptosis. By such treatment, the protein level of inducible nitric oxide
      synthase (iNOS) was doubled and cellular oxidants, including nitric oxide,
      superoxide, and their derivatives, were increasingly produced. In MG132-treated
      cells, the increase in iNOS-derived oxidants was responsible for mitochondrial
      depolarization and caspase-dependent apoptosis, but was insignificant in G2/M
      arrest. The amount of iNOS was negatively correlated with that of manganese
      superoxide dismutase (MnSOD). Whereas iNOS activity was inhibited by
      aminoguanidine, cellular MnSOD levels as well as mitochondrial membrane
      potentials were upregulated, and consequentially G2/M arrest and apoptosis were
      thoroughly reversed. It is suggested that cells rich in functional mitochondria
      possess improved proteasome activity, which antagonizes the cytotoxic and
      cytostatic effects of MG132. In contrast to iNOS, endothelial NOS-driven cGMP
      dependent signaling promoted mitochondrial function and survival of MG132
      stressed cells. In conclusion, the functional interplay of proteasomes and
      mitochondria is crucial for leukemic cell growth, wherein iNOS plays a key role.

PMID- 24909617
TI  - Regional upregulation of hippocampal melatonin MT2 receptors by valproic acid:
      therapeutic implications for Alzheimer's disease.
AB  - We have reported that clinically relevant concentrations of valproic acid (VPA)
      upregulate the G protein-coupled melatonin MT1 receptor in rat C6 glioma cells,
      and both MT1 and MT2 receptors in the rat hippocampus. The melatonin MT2 receptor
      is relatively enriched in the hippocampus, where it is thought to be involved in
      modulating synaptic plasticity and cognitive function. Importantly, a significant
      decrease in MT2 expression has been observed in the hippocampus of Alzheimer's
      patients. Therefore, we examined whether the global upregulation of this receptor
      (and also the MT1) by VPA, observed in earlier RT-PCR and real time PCR studies,
      could be localized to more discrete hippocampal regions, which are involved in
      cognitive function. In situ hybridization of rat brain slices, following chronic
      VPA treatment (3mg/mL or 4mg/mL in drinking water), revealed a significant
      upregulation of the MT2 receptor mRNA in the CA1, CA2, CA3 and dentate gyrus (DG)
      regions of the rat hippocampus. In contrast, the MT1 receptor was not detected in
      the hippocampus by in situ hybridization. The significant induction of melatonin
      MT2 receptor expression by VPA in hippocampal regions involved in learning,
      memory and/or neural stem cell proliferation, suggests that a combinatorial
      therapeutic strategy involving VPA together with melatonin or other MT2 agonists,
      would be beneficial in neurodegenerative disorders such as Alzheimer's disease. 

PMID- 24909618
TI  - Oxygen therapy does not increase production and damage induced by reactive oxygen
      species in focal cerebral ischemia.
AB  - Oxygen therapy with hyperbaric oxygen (HBO) or normobaric hyperoxia (NBO)
      improves outcome in experimental cerebral ischemia. However, an increased
      formation of reactive oxygen species (ROS) may be an undesirable side effect of
      oxygen therapy. We investigated the effect of both oxygen therapies on ROS
      production and adverse effects in murine focal ischemia. 25 min after 90 min
      filament-induced middle cerebral artery occlusion (MCAO), mice breathed either
      air, 100% O2 (NBO), or 100% O2 at 3 ata (HBO) for 60 min. ROS were depicted on
      tissue sections after preischemic injection of hydroethidine, a marker of in vivo
      superoxide production. Moreover, infarct sizes were quantified in experiments
      using peroxybutinitrite (PBN) in mice treated with HBO. Effects of oxygen therapy
      were also tested in superoxide 2 knock-out mice. Both NBO and HBO significantly
      reduced superoxide radicals compared to air. Application of PBN had no additional
      protective effect when combined with HBO. Infarct volumes did not differ among
      SOD2 knock-out mice receiving air (34.0 +/- 19.6mm(3)), NBO (35.4 +/- 14.3mm(3))
      or HBO (33.4 +/- 12.2mm(3)). In conclusion, brief episodes of oxygen therapy do
      not appear to promote damage inflicted by ROS in experimental stroke.

PMID- 24909619
TI  - Sex differences in Delta(9)-tetrahydrocannabinol metabolism and in vivo
      pharmacology following acute and repeated dosing in adolescent rats.
AB  - Mechanisms that may underlie age and sex differences in the pharmacological
      effects of cannabinoids are relatively unexplored. The purpose of the present
      study was to determine whether sex differences in metabolism of Delta(9)
      tetrahydrocannabinol (THC), similar to those observed previously in adult rats,
      also occurred in adolescent rats and might contribute to age and sex differences
      in its in vivo pharmacology. Male and female adolescent rats were exposed to THC
      acutely or repeatedly for 10 days. Subsequently, some of the rats were sacrificed
      and blood and brain levels of THC and one of its metabolites, 11-hydroxy-Delta(9)
      THC (11-OH-THC), were measured. Other rats were evaluated in a battery of in vivo
      tests that are sensitive to cannabinoids. Concentrations of 11-OH-THC in the
      brains of female adult and adolescent rats exceeded those observed in male
      conspecifics, particularly after repeated THC administration. In contrast, brain
      levels of THC did not differ between the sexes. In vivo, acute THC produced dose
      related hypothermia, catalepsy and suppression of locomotion in adolescent rats
      of both sexes, with tolerance developing after repeated administration. With a
      minor exception, sex differences in THC's effects in the in vivo assays were not
      apparent. Together with previous findings, the present results suggest that sex
      differences in pharmacokinetics cannot fully explain the patterns of sex
      differences (and lack of sex differences) in cannabinoid effects across
      behaviors. Hormonal and/or pharmacodynamic factors are also likely to play a
      role. 

PMID- 24909620
TI  - Amyloid-beta (Abeta1-42)-induced paralysis in Caenorhabditis elegans is reduced
      by restricted cholesterol supply.
AB  - Alzheimer' disease is a neurodegenerative disorder characterized by the
      misfolding and aggregation of amyloid beta (Abeta). This process is influenced
      through supply of cholesterol via apolipoproteins to neurons. In the present
      study, we used the transgenic Caenorhabditis elegans strain CL2006, which
      expresses Abeta1-42 under control of a muscle-specific promoter, to test the
      effects of the apolipoprotein B homologue vitellogenin-6 on paralysis. Knockdown
      of vitellogenin-6 using RNA-interference (RNAi) recently was shown to
      significantly reduce cholesterol absorption in C. elegans, and both, RNAi for
      vitellogenin-6 or lowering the cholesterol concentration in the medium was
      associated with reduced Abeta-aggregation and paralysis in the nematodes. The
      effects of both interventions are mediated through the inhibition of the
      steroidal-signaling pathway since knockdown of its key factors DAF-9 or DAF-12
      reduced paralysis independent of the cholesterol concentration and without
      additive effects by vitellogenin-6 RNAi. Double-RNAi for daf-12 and the
      downstream target of insulin-signaling, the foxo transcription factor daf-16,
      revealed that the paralysis-triggering effects of daf-16 RNAi were dominant over
      the preventive effects of daf-12 RNAi. Identical observations were made when the
      transcriptional co-activators of DAF-16, ftt-2 or par-5 were knocked down instead
      of daf-16. In conclusion, interactions between the steroidal and insulin
      signaling pathways were identified in Abeta1-42 expressing CL2006, where
      cholesterol deprivation inhibits steroidal-signaling and thereby activates DAF-16
      signaling. Those effects were associated with a reduced Alzheimer phenotype in
      the nematodes, i.e. reduced protein aggregation and paralysis. 

PMID- 24909621
TI  - Editor's perspectives--June 2014.

PMID- 24909622
TI  - Differential Response family assessments: listening to what parents say about
      service helpfulness.
AB  - An increasing number of Child Protective Services (CPS) systems are implementing
      Differential Response (DR) approaches in which lower-risk families are served
      through a family assessment response that emphasizes a family centered approach
      and the provision of concrete and preventative services. Quantitative survey data
      collected from parents suggests that those who receive family assessments are
      more engaged, receive more concrete services, and have higher overall
      satisfaction than those who receive a traditional investigation; yet little is
      known about which services provided through a family assessment are most helpful
      to parents. This qualitative study sought input from 20 parents who received a DR
      family assessment response in order to provide an in-depth analysis of which
      aspects of their CPS experience they perceived as most helpful. Results suggest
      that a positive and emotionally supportive relationship with the caseworker was
      of utmost significance. Other caseworker-provided services were described as
      helpful, particularly those that helped parents establish or improve
      relationships with others, including advocacy with other service providers,
      mediation of family disagreements, and coaching on parenting or relationship
      skills. Material support, such as providing cash assistance for rent or
      furniture, was helpful when received but occurred less frequently and was
      sometimes a source of frustration when accompanied by lengthy waits for
      assistance. These findings have implications for CPS practice, including
      enhancing caseworkers' relationship-building and engagement skills through pre
      service educational coursework and in-service trainings; allowing caseworkers
      adequate time to develop supportive relationships with parents; and reducing the
      institutional barriers that delay the provision of concrete support. 

PMID- 24909623
TI  - Development of a risk score to stratify symptomatic adults referred for
      colonoscopy.
AB  - BACKGROUND AND AIM: With an increasing burden on overstretched colonoscopy
      services, a simple risk score for significant pathology in symptomatic patients
      may aid in the prioritization of patients. METHODS: A derivative study of a risk
      score model for colonic neoplasia (colorectal carcinoma [CRC] and advanced
      adenoma) and CRC alone was conducted in symptomatic adults referred for an index
      colonoscopy. The accuracy of the final model was assessed by the area under the
      curve (AUC) of the receiver operating characteristic curve and the Hosmer
      Lemeshow goodness-of-fit statistic. RESULTS: A total of 1013 subjects (mean age
      59.9 +/- 13.7 years, 52.3% females) from a multi-ethnic Asian background (Chinese
      56%, Malay 20.4%, Indian 21.5%) were recruited. Colonic neoplasia and CRC were
      identified in 175 (17.3%) and 114 (11.3%) cases, respectively. Risk scores were
      assigned to individual factors identified in a logistic regression model of both
      demographic (age, gender, ethnicity, education level, smoking history, Aspirin
      use) and clinical symptoms (change in bowel habit, bloody stool, weight loss,
      appetite loss, lethargy). The risk score for each patient was the sum of their
      individual risk factors. The AUC of the risk score for colonic neoplasia and CRC
      was 0.76 (Hosmer-Lemeshow goodness-of-fit statistic of P = 0.745) and 0.83
      (Hosmer-Lemeshow goodness-of-fit statistic of P = 0.982), respectively.
      CONCLUSION: A simple risk score for colonic neoplasia and CRC may be able to
      prioritize colonoscopy referrals in symptomatic subjects from a multi-ethnic
      background. A further study to validate this scoring system is required.

PMID- 24909624
TI  - Paired study of 172 cases of nasopharyngeal carcinoma with or without
      dermatomyositis.
AB  - CONCLUSION: The prognosis and late adverse effects of radiotherapy (RT) in the
      patients with nasopharyngeal carcinoma (NPC) with or without dermatomyositis (DM)
      were similar, although the NPC patients with DM had higher Epstein-Barr virus
      (EBV) VCA-IgA titers and more severe acute side effects. Gender, TNM stage, and
      chemotherapy were independent prognostic factors of overall survival for NPC with
      DM. Glucocorticoid treatment did not affect the survival of NPC patients with DM.
      OBJECTIVES: We evaluated the clinical characteristics, prognosis, and differences
      in the toxicity of RT in patients with NPC with or without DM. METHODS: A paired
      study of 172 NPC cases with DM (DM group) or without DM (control group) from Sun
      Yat-sen University Cancer Center was conducted. RESULTS: The DM group had higher
      EBV VCA-IgA titers than the control group (p = 0.017) and more acute adverse
      effects of RT (p < 0.001). No significant differences in the overall survival or
      late adverse effects were found between the two groups. Gender, TNM stage, and
      chemotherapy were independent prognostic factors for the overall survival in the
      DM group. No significant differences in the overall survival were found between
      the patients in the DM group who were taking glucocorticoids and those who were
      not.

PMID- 24909625
TI  - Amplitude modulated vestibular evoked myogenic responses: a study of carrier and
      modulating frequencies.
AB  - CONCLUSION: Responses with greater amplitude were recorded when carrier
      frequencies were modulated at 37, 40, and 43 Hz. These responses can be recorded
      even in patients with significant sensorineural hearing loss, from the
      sternocleidomastoid (SCM) muscle for a 500 Hz tone, 100% modulated at 40 Hz.
      OBJECTIVE: To determine the best carrier and modulating frequencies to evoke
      steady-state myogenic responses. METHODS: The present study investigated 156 ears
      of 78 normal-hearing young adults, with carrier frequencies of 250, 500, and 1000
      Hz, modulated at 20, 37, 40, 43, 70, 77, and 80 Hz, with an intensity of 95 dBA.
      Furthermore, we observed responses evoked by stimulus carrier frequency of 500
      Hz, modulated at 40 Hz, with an intensity of 95 dBA in a group of five subjects
      with severe sensorineural loss. RESULTS: Responses were found for all stimuli
      studied (p < 0.01). Modulated stimuli at frequencies of 37, 40, and 43 Hz evoked
      better steady-state vestibular evoked myogenic potential (S-VEMP) (p < 0.05). No
      statistically significant differences were found between the group of normal
      hearers and the group of subjects with hearing loss (p = 0.431), for the stimulus
      used.

PMID- 24909626
TI  - Improvement of facial scar appearance and microcirculation by autologous
      lipofilling.
AB  - BACKGROUND: Autologous lipofilling has become a standard procedure for many
      indications in plastic surgery. Single-case studies have reported improvements in
      scars, especially in burn patients, after autologous lipofilling. Despite its
      widespread use, little is known about the mechanisms responsible for this
      improvement. It is hypothesized that the mesenchymal stem cells and numerous
      growth factors contained in the lipoaspirate contribute to the skin and scar
      remodeling. MATERIAL AND METHODS: Between 2008 and 2012, 35 facial scars (n=35)
      on 26 patients (n=26) were treated by autologous lipofilling. The preoperative
      examinations and postoperative follow-up included use of the patient and observer
      scar assessment scale (POSAS), photo documentation, and laser Doppler
      spectrometry (O2C) measurements of tissue oxygen saturation, hemoglobin levels,
      and microcirculation on the second, seventh, and ninetieth postoperative days.
      RESULTS: The scar quality improved in all cases, leading to a high patient
      satisfaction rate at the final follow-up examination. The POSAS scores were
      significantly increased for pain (p=0.0331), color (p=0.0007), stiffness
      (p=0.0030), irregularity (p=0.0039), pigmentation (p=0.0282), and pliability
      (p=0.0404). In addition, we observed increased hemoglobin levels in the early
      postoperative period (second day) and a reduction in the microcirculation, which
      normalized to the preoperative values after 7-90 days. CONCLUSIONS: We
      demonstrated that autologous lipofilling represents a valuable technique for the
      treatment of facial scars. Further prospective observational studies are needed
      to better understand the mechanisms leading to scar enhancement and to make this
      procedure more reliable and predictable for patients.

PMID- 24909627
TI  - Frey's syndrome following total ear reconstruction in hemifacial microsomia.

PMID- 24909629
TI  - But is it an ALT flap? Previously-unreported anomalous medially-based vascular
      supply to anterolateral thigh flap.

PMID- 24909628
TI  - Effect of maxillary alveolar reconstruction on nasal symmetry of cleft lip and
      palate patients: a study comparing iliac crest bone graft and recombinant human
      bone morphogenetic protein-2.
AB  - BACKGROUND: Recombinant human bone morphogenetic protein (rhBMP)-2 has been used
      in some craniofacial centers worldwide. However, its influence on nasal
      morphology is unknown. Thus, the objective of this investigation was to assess
      the effect of maxillary alveolar reconstruction on nasal position and symmetry in
      unilateral complete cleft lip patients who underwent traditional iliac crest bone
      grafting transferring versus reconstruction using rhBMP-2. METHODS: Nineteen
      unilateral complete cleft lip patients were randomly divided into two groups. In
      group 1, patients underwent traditional iliac crest bone grafting transferring (n
      = 11) and in group 2, patients underwent alveolar reconstruction using collagen
      matrix with lyophilized rhBMP-2 (n = 8). Computerized tomography (CT) imaging was
      performed preoperatively and at 6 months postoperatively using a previously
      standardized protocol. Linear distances using anatomic landmarks were performed
      using tridimensional CT data reformatted by the OsiriX((r)) software.
      Quantitative and qualitative measurements to assess intra- and inter-group nasal
      position modifications were performed. RESULTS: Intra-group pre- and
      postoperative comparisons showed significant differences (p < 0.05) in two linear
      measurements of group 1, while group 2 did not present a difference (p > 0.05).
      Group 2 presented significant postoperative enhancement (p < 0.05) in the
      quantitative nasal symmetry in one measurement. Qualitative analysis showed
      postoperative nasal symmetry enhancement in 75% of the measurements of group 2
      and 36% of group 1. There was no statistically significant difference in the
      inter-group comparisons. CONCLUSIONS: Our study demonstrated that both groups
      showed similar effect on nasal symmetry.

PMID- 24909630
TI  - National commissioning guidelines: body contouring surgery after massive weight
      loss.
AB  - The guidelines for body contouring reconstructive surgery present an evidence
      based guide for management of redundant tissue after massive weight loss. A
      standardised referral pathway to ensure safe and equitable patient care on the
      National Health Service (NHS) throughout England is recommended. A database of
      all patients for research purposes is suggested. 

PMID- 24909631
TI  - Education, safe drinking practices and fetal alcohol spectrum disorder in the
      Kimberley region of Western Australia.
AB  - AIM: There are alarming rates of fetal alcohol spectrum disorder (FASD) in the
      Kimberley region of Western Australia despite numerous international studies
      demonstrating the links between alcohol consumption during pregnancy and FASD.
      The aim of this research was to help determine factors that may be associated
      with correct knowledge about safe drinking practices during pregnancy, with these
      factors used to help inform future interventions. METHOD: Ninety-nine residents
      (40 males, 59 females, 39% of which self-identified as Indigenous) from the
      Kimberley region (Broome and smaller remote communities) completed a survey
      examining knowledge of currently recommended safe drinking practices during
      pregnancy and knowledge of the outcomes for children with FASD over a period of
      approximately 2 months. RESULTS: The results revealed that education level (i.e.
      not completing high school through to completing university) is the biggest
      predictor (beta = 0.44, P < 0.01) of knowledge of safe drinking practices during
      pregnancy, and having heard of FASD (beta = 0.67, P < 0.001) was the biggest
      predictor of knowledge of outcomes for children with FASD. Other variables such
      as age, sex, Indigenous status and income level were not as important.
      CONCLUSIONS: These findings suggest that early education regarding the
      consequences of alcohol consumption for women of childbearing age should be
      paramount in this or similar communities. Suggestions for targeted interventions
      are discussed in light of these findings.

PMID- 24909632
TI  - Forms of vitality play in infancy.
AB  - In this paper we report a qualitative study based on the constant comparative
      method to initiate the systematic study of forms of vitality play. This is an
      unnoticed non-figurative play frame linked to early social play and temporal arts
      in which child and adult elaborate the dynamics of their own movements and sounds
      in a repetition-variation form. In the introduction we present the theoretical
      underpinnings and the sporadic observations we have done in previous studies.
      Then, by the iterative observations of the recorded material of a longitudinal
      case study on play during the third year of life, we generated the general
      category of forms of vitality play and four subcategories of display modes of
      forms of vitality play (improvised forms of vitality play, ritualized forms of
      vitality play, forms of vitality play combined with pretend play, and forms of
      vitality play combined with role playing) which are illustrated with descriptive
      narratives. We discuss the properties of the developed categories, the limits of
      the present study, and the need to continue systematizing the research on this
      playful activity. 

PMID- 24909634
TI  - Contraceptive awareness and birth control selection in female kidney and liver
      transplant recipients.
AB  - OBJECTIVE(S): Interest has increased regarding the issue of contraception in
      transplant recipients. The purpose of this study was to assess birth control
      selection and the role of contraceptive counseling sessions in female kidney
      transplant (KT) and liver transplant (LT) recipients. STUDY DESIGN: A cross
      sectional single-center survey study of 217 female organ recipients (KT, 137 and
      LT, 80), aged 18-45 years, met the study criteria. Patients were asked 43
      questions regarding their pre- and posttransplantation use of contraceptive
      methods, birth control awareness, contraception counseling and the factors
      determining the selection of effective contraception (hormonal contraception,
      intrauterine devices and female sterilization). RESULTS: Thirty-three percent
      (5/15) of patients who had undergone the transplantation within 1 year prior to
      study inclusion were unaware of the necessity to use contraception. Both of the
      groups studied did not differ significantly in terms of the rates of pre- and
      posttransplantation consultations on effective contraception (KT: 26% vs. 34%;
      p=0.153 and LT 38% vs. 35%; p=0.729). Effective posttransplantation contraception
      was used by one in three patients, as indicated by posttransplantation
      consultations (KT: 30% vs. LT: 29%; p=0.910). The following factors affected the
      posttransplantation use of effective contraception: the presence of
      posttransplantation counseling on effective contraception [odds ratio (OR): 6.67;
      95% confidence interval (CI): 2.12-20.1] and infrequent sexual activity prior to
      transplantation (OR: 0.56; 95% CI: 0.35-0.89). CONCLUSION(S): The selection of
      effective contraception in KT and LT recipients remain suboptimal. Despite the
      low numbers of women who received contraceptive counseling in this study,
      consultation was nonetheless associated with choosing an effective method of
      contraception. IMPLICATION: Current literature and data regarding contraception
      among female organ transplant recipients remain limited and are predominantly
      limited to a single population. The purpose of the study was to assess the level
      of satisfaction and the reasons underlying birth control selection in female
      kidney and LT recipients.

PMID- 24909635
TI  - Pull and pray or extra protection? Contraceptive strategies involving withdrawal
      among US adult women.
AB  - OBJECTIVE: Research assessing contraceptive use often focuses on the most
      effective method used and suggests that very few women rely on withdrawal. We
      adopted a new measurement strategy in an attempt to measure contraceptive
      practices and withdrawal in particular. STUDY DESIGN: We collected data from a
      national sample of 4634 US women aged 18-39; the survey was administered online
      in November and December 2012. We obtained information about recent use of
      hormonal methods and coital methods using two separate items, and we placed
      withdrawal first on the list of coital methods. The analysis examines several
      measures of withdrawal use in the last 30 days: most effective method used, any
      use, use with other methods and withdrawal "method mix." RESULTS: Among women at
      risk of unintended pregnancy, 13% reported that withdrawal was the most effective
      method used in the last 30 days, but 33% had used withdrawal at least once. Most
      women who used withdrawal had also used a hormonal or long-acting method (13% of
      the sample) or condoms (11%) in the last 30 days, and a minority reported using
      only withdrawal (12%). Younger women, women in dating relationships and women
      strongly motivated to avoid pregnancy had some of the highest levels of "dual"
      use of withdrawal with condoms or highly effective methods. CONCLUSION: Many
      women and couples in our sample used withdrawal in combination, or rotation, with
      condoms and highly effective methods. Findings suggest that some people who use
      withdrawal may be more versus less vigilant about pregnancy prevention.
      IMPLICATIONS: Health care providers who discuss contraception should include
      withdrawal in these conversations. A substantial minority of individuals has used
      it recently, and many appear to be using it as a backup or secondary method. If
      dual use were more widespread, it could help reduce the incidence of unintended
      pregnancy.

PMID- 24909637
TI  - Hybrid sensors based on colour centres in diamond and piezoactive layers.
AB  - The ability to measure weak signals such as pressure, force, electric field and
      temperature with nanoscale devices and high spatial resolution offers a wide
      range of applications in fundamental and applied sciences. Here we present a
      proposal for a hybrid device composed of thin film layers of diamond with colour
      centres and piezoactive elements for the transduction and measurement of physical
      signals. The magnetic response of a piezomagnetic layer to an external stress or
      a stress induced by a signal is shown to affect significantly the spin properties
      of nitrogen-vacancy centres in diamond. Under ambient conditions, realistic
      environmental noise and material imperfections, we show that this hybrid device
      can achieve significant improvements in sensitivity over the pure diamond-based
      approach in combination with nanometre-scale spatial resolution. Furthermore, the
      proposed hybrid architecture offers novel possibilities for engineering strong
      coherent couplings between nanomechanical oscillator and solid state spin qubits.

PMID- 24909636
TI  - Effect of oral administration of a continuous 18 day regimen of meloxicam on
      ovulation: experience of a randomized controlled trial.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is expressed in all female reproductive
      organs. Therefore, inhibitors of COX-2 may affect reproductive function. We
      evaluated the effect of extended administration of meloxicam on ovulation and the
      menstrual cycle. Our hypothesis was that meloxicam administered from menstrual
      cycle day 5- 22 could interfere with follicular rupture, without disrupting the
      menstrual cycle, and could be a potential non-hormonal contraceptive method.
      METHODS: The study was conducted in 56 healthy sterilized women. Before the onset
      of treatment and after the end of treatment, participants were observed during a
      control cycle to ensure that they had progesterone (P4) serum levels (>12 nmol/l)
      consistent with ovulation. Participants were treated for 18 days, during three
      consecutive cycles. They were randomized to 15 or 30 mg/day. The menstrual cycle
      was monitored with serial ultrasound and hormone assays in blood. RESULTS: Fifty
      six volunteers completed the study. In 55% of cycles treated with 15 mg/day and
      in 78% of cycles treated with 30 mg/day (p<0.001) we observed dysfunctional
      ovulation defined as follicular rupture not preceded 24-48 h earlier by an LH
      peak or preceded by a blunted LH peak (<21 IU/l) or not followed by an elevated
      serum P4 level >12 nmol/l. Ovulation was observed in 44.6% and in 21.7% of women
      in the lower dose group and the higher dose group, respectively. There were no
      differences between the two doses in other parameters measured. There were no
      serious adverse events and adverse events were not different between doses or
      between control and treated cycles. CONCLUSIONS: Although administration of
      meloxicam on menstrual cycle days 5- 22 resulted in a dose-dependent inhibition
      of ovulation, more than 20% of subjects had normal ovulation with the highest
      dose. IMPLICATIONS: Previous studies have shown that oral meloxicam can delay
      follicle rupture. This study investigated daily oral meloxicam as a non-hormonal
      contraceptive. Since ovulation occurs in over 20% of cycles even with a high dose
      of 30 mg daily, it is not likely that the approach would be a highly effective
      contraceptive strategy.

PMID- 24909638
TI  - Effect of Twist and Bmi1 on intraductal papillary mucinous neoplasm of the
      pancreas.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a well-established
      entity among pancreatic neoplasms that ranges from low-grade dysplasia to
      invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor
      progression in various cancers. Moreover, Notch signaling is one of the important
      upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes
      pathological progression of IPMN. AIM: We evaluated the expression of EMT
      promoting transcription factors Twist and B cell-specific Moloney murine leukemia
      virus insertion site 1 (Bmi1) in IPMN. METHODS: Patients who underwent resections
      at our institute and its affiliated hospital were enrolled in this study (n =
      35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in
      resected specimens was investigated by immunohistochemistry. Expression of these
      proteins was compared with the clinicopathological factors and patient survival.
      RESULTS: Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of
      IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs
      with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that
      in IPMNs with low-grade dysplasia. High expression of Twist was correlated with
      Jagged1 expression and inversely correlated with expression of E-cadherin (P =
      0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was
      significantly higher in the group that showed simultaneous high expression of
      Twist and Bmi1 (P < 0.05). CONCLUSIONS: Expression of Twist and Bmi1 is
      associated with aggressiveness and poor prognoses of IPMN through EMT promotion
      that might be induced by Notch signaling.

PMID- 24909639
TI  - Scan for Motifs: a webserver for the analysis of post-transcriptional regulatory
      elements in the 3' untranslated regions (3' UTRs) of mRNAs.
AB  - BACKGROUND: Gene expression in vertebrate cells may be controlled post
      transcriptionally through regulatory elements in mRNAs. These are usually located
      in the untranslated regions (UTRs) of mRNA sequences, particularly the 3'UTRs.
      RESULTS: Scan for Motifs (SFM) simplifies the process of identifying a wide range
      of regulatory elements on alignments of vertebrate 3'UTRs. SFM includes
      identification of both RNA Binding Protein (RBP) sites and targets of miRNAs. In
      addition to searching pre-computed alignments, the tool provides users the
      flexibility to search their own sequences or alignments. The regulatory elements
      may be filtered by expected value cutoffs and are cross-referenced back to their
      respective sources and literature. The output is an interactive graphical
      representation, highlighting potential regulatory elements and overlaps between
      them. The output also provides simple statistics and links to related resources
      for complementary analyses. The overall process is intuitive and fast. As SFM is
      a free web-application, the user does not need to install any software or
      databases. CONCLUSIONS: Visualisation of the binding sites of different classes
      of effectors that bind to 3'UTRs will facilitate the study of regulatory elements
      in 3' UTRs.

PMID- 24909640
TI  - Molecular packing and electronic processes in amorphous-like polymer bulk
      heterojunction solar cells with fullerene intercalation.
AB  - The interpenetrating morphology formed by the electron donor and acceptor
      materials is critical for the performance of polymer:fullerene bulk
      heterojunction (BHJ) photovoltaic (PV) cells. In this work we carried out a
      systematic investigation on a high PV efficiency (>6%) BHJ system consisting of a
      newly developed 5,6-difluorobenzo[c] thiadiazole-based copolymer, PFBT-T20TT, and
      a fullerene derivative. Grazing incidence X-ray scattering measurements reveal
      the lower-ordered nature of the BHJ system as well as an intermixing morphology
      with intercalation of fullerene molecules between the PFBT-T20TT lamella. Steady
      state and transient photo-induced absorption spectroscopy reveal ultrafast charge
      transfer (CT) at the PFBT-T20TT/fullerene interface, indicating that the CT
      process is no longer limited by exciton diffusion. Furthermore, we extracted the
      hole mobility based on the space limited current (SCLC) model and found that more
      efficient hole transport is achieved in the PFBT-T20TT:fullerene BHJ as compared
      to pure PFBT-T20TT, showing a different trend as compared to the previously
      reported highly crystalline polymer:fullerene blend with a similar intercalation
      manner. Our study correlates the fullerene intercalated polymer lamella
      morphology with device performance and provides a coherent model to interpret the
      high photovoltaic performance of some of the recently developed weakly-ordered
      BHJ systems based on conjugated polymers with branched side-chain. 

PMID- 24909642
TI  - Psychological outcomes in critically ill patients receiving renal replacement
      therapy: a matched-pairs analysis.
AB  - We conducted a single-centre observational study over five years to assess the
      impact of renal replacement therapy on the psychological health of survivors of
      critical illness. We hypothesised that the added burden of renal replacement
      would increase the prevalence and severity of anxiety, depression and stress
      reactions in these patients, compared with matched pairs (matched for age, sex
      and APACHE II score) who did not receive renal replacement. Participants
      completed postal questionnaires. A total of 342 patients with acute kidney injury
      received renal replacement. One hundred and seventy-nine (52.3%) survived to
      hospital discharge, and 161 (47.1%) were alive at 90 days. Seventy-seven (47.8%
      of survivors) completed questionnaires. We found 77 matches for the Hospital
      Anxiety and Depression Scale analysis and 72 for the Impact of Events Scale
      analysis. Clinically relevant symptoms of psychiatric morbidity were common, with
      anxiety and depression affecting 49 (63.6%) patients and stress reactions
      affecting 24 (33.3%) patients. Mean scores (95% CI) were 11.4 (9.6-13.2) and 20.1
      (15.7-24.6), respectively. On multivariate analysis, we found no significant
      differences between renal replacement patients and controls, in either the
      frequency or severity of these symptoms. 

PMID- 24909641
TI  - Identification of protein succination as a novel modification of tubulin.
AB  - Protein succination is a stable post-translational modification that occurs when
      fumarate reacts with cysteine residues to generate 2SC [S-(2-succino)cysteine].
      We demonstrate that both alpha- and beta-tubulin are increasingly modified by
      succination in 3T3-L1 adipocytes and in the adipose tissue of db/db mice.
      Incubation of purified tubulin from porcine brain with fumarate (50 mM) or the
      pharmacological compound DMF (dimethylfumarate, 500 MUM) inhibited polymerization
      up to 35% and 59% respectively. Using MS we identified Cys347alpha, Cys376alpha,
      Cys12beta and Cys303beta as sites of succination in porcine brain tubulin and the
      relative abundance of succination at these cysteine residues increased in
      association with fumarate concentration. The increase in succination after
      incubation with fumarate altered tubulin recognition by an anti-alpha-tubulin
      antibody. Succinated tubulin in adipocytes cultured in high glucose compared with
      normal glucose also had reduced reactivity with the anti-alpha-tubulin antibody;
      suggesting that succination may interfere with tubulin-protein interactions. DMF
      reacted rapidly with 11 of the 20 cysteine residues in the alphabeta-tubulin
      dimer, decreased the number of free thiols and inhibited the proliferation of 3T3
      L1 fibroblasts. Our data suggest that inhibition of tubulin polymerization is an
      important undocumented mechanism of action of DMF. Taken together, our results
      demonstrate that succination is a novel post-translational modification of
      tubulin and suggest that extensive modification by fumarate, either
      physiologically or pharmacologically, may alter microtubule dynamics. 

PMID- 24909643
TI  - Equal access to health care may diminish the differences in outcome between
      native and immigrant patients with type 1 diabetes.
AB  - BACKGROUND/OBJECTIVE: Previous studies have found that ethnicity influences
      glycemic control. We hypothesized that differences between Nordic and non-Nordic
      patients are less pronounced for children with type 1 diabetes in high incidence
      countries in Northern Europe. RESEARCH DESIGN AND METHODS: We investigated
      patients aged 0-15 yr in national pediatric registers in Denmark (D), Iceland
      (I), Norway (N), and Sweden (S) (2006-2009). Ethnic origin was defined by
      maternal country of birth as being Nordic or non-Nordic (other countries).
      RESULTS: The cohort (n = 11,908, 53.0% boys, onset age 7.7 (3.9) yr, diabetes
      duration 6.1 (3.6) yr, [mean, (SD)]) comprised 921 (7.7%) non-Nordic patients.
      The frequencies of non-Nordic patients according to country of residence were:
      5.7% (D), 2.7% (I), 5.5% (N), and 9.4% (S). Sex distribution and BMI z-score did
      not differ between Nordic and non-Nordic patients, but non-Nordic patients were
      0.5 yr younger at onset than Nordic patients (p < 0.0006). Non-Nordic patients
      had a lower number of daily insulin bolus injections and higher daily insulin
      doses compared to their Nordic peers. Patients of non-Nordic origin had slightly
      higher HbA1c levels (0.6-2.9 mmol/mol, p < 0.001) and, with the exception of
      Norway, were less frequently treated with CSII (p = 0.002) after adjusting for
      confounders. CONCLUSIONS: The reported differences in glycemic regulation between
      Nordic and non-Nordic type 1 diabetes children and adolescents in four Nordic
      countries are diminutive, but persist after accounting for treatment intensity.

PMID- 24909644
TI  - High-intensity physical activity, stable relationship, and high education level
      associate with decreasing risk of erectile dysfunction in 1,000 apparently
      healthy cardiovascular risk subjects.
AB  - INTRODUCTION: Erectile dysfunction (ED) is especially common in men with
      cardiovascular diseases (CVDs). However, the data are scarce concerning
      populations without manifested CVD. AIM: The aim of this study was to describe
      factors associated with ED, especially those associated with decreasing risk of
      ED, in men with cardiovascular risk factors but without CVD, diabetes, or chronic
      renal disease. METHODS: In 2004 to 2007, a cross-sectional population-based
      sample of men 45 to 70 years old in two rural towns in Finland was collected. Men
      with previously diagnosed CVD, diabetes, or kidney disease were not invited to
      the study. In total 1,000 eligible men with cardiovascular risk factors, i.e.,
      central obesity, high scores in the Finnish Diabetes Risk Score, high blood
      pressure, antihypertensive medication, or family history of coronary heart
      disease, myocardial infarction, or stroke, were included in the analysis.
      Questionnaires, clinical measurements, and laboratory tests were obtained. The
      prevalence of ED was studied comparing the means, and risk factors were studied
      using multivariate logistic regression analysis. MAIN OUTCOME MEASURES: The rate
      of ED was defined by the International Index of Erectile Function short form
      (IIEF-5) and by two questions (2Q) about the ability to achieve and to maintain
      an erection. RESULTS: The prevalence of ED was 57% or 68% using IIEF-5 or 2Q,
      respectively. Age (odds ratio [OR]: up to 9.16; 95% confidence interval [CI],
      5.00-16.79; P < 0.001), smoking (OR: 1.41; 95% CI, 1.04-1.91; P = 0.028),
      depressive symptoms (OR: 4.04 for moderate and severe; 95% CI,1.22-13.45; P =
      0.001), high-intensity physical activity (OR: 0.50; 95% CI, 0.29-0.86; P =
      0.045), high education (OR: 0.52; 95% CI, 0.33-0.83; P = 0.013), and stable
      relationship (OR: 0.43; 95% CI, 0.21-0.88; P = 0.046) were associated with ED.
      CONCLUSIONS: In apparently healthy men with cardiovascular risk factors,
      decreasing risk of ED is associated with high-intensity physical activity, stable
      relationship, and high education level.

PMID- 24909645
TI  - The influence of fluid and crystallized intelligence on the development of
      knowledge and skills.
AB  - BACKGROUND: Cattell's Gf-Gc distinction is quite generally recognized. However,
      the developmental part of the Gf-Gc theory of intelligence has not gained the
      same recognition. Results are inconsistent, but recent discussions emphasize the
      importance of homogeneity of samples with regard to education and language when
      investigating the developmental Investment theory. AIMS: The aim of this study
      was to investigate the influence of Gf and Gc on the development of knowledge and
      skills in a sample of children in compulsory school who are homogenous with
      regard to level of education, age, and cultural background. SAMPLE: Totally,
      9,002 individuals from the evaluation through follow-up database born in 1972 and
      who left compulsory school in 1988 were included. These individuals were followed
      up in Grades 3, 6, and 9. METHODS: Structural equation modelling was used, and
      autoregressive path models were fitted. All modelling was performed using Mplus
      version 6.1. RESULTS: In the first step, a path model with a simplex structure
      was defined. However, a second model with direct relations of Gf on Gc in Grades
      6 and 9 had better model fit, suggesting a continuous influence of Gf on Gc.
      However, no direct influence of Gf was found for the subject grades. CONCLUSION:
      Due to the continuous influence of Gf on the measures of Gc throughout compulsory
      school, support for Cattell's (1987) Investment theory was found.

PMID- 24909646
TI  - Psychiatric comorbidities in 3207 patients with hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory
      disease affecting skin that bears apocrine glands. Only anecdotal reports and a
      few small studies have demonstrated a possible association between HS and
      depression, but these studies were uncontrolled or were based on small sample
      sizes. To the best of our knowledge, the association between HS and other
      psychiatric disorders has never been investigated. OBJECTIVES: To investigate the
      association between HS and psychiatric disorders: depression, anxiety, psychoses,
      schizophrenia and bipolar disorder. METHODS: A cross-sectional study was
      conducted utilizing the database of Clalit Health Services (over 4,100,000
      patients). Case patients were defined as having HS when diagnosed by a
      dermatologist. Control patients without HS were age and gender matched in a 2 : 1
      manner. The proportions of patients with psychiatric diseases were compared
      between patients with and without HS. The association between HS and psychiatric
      diseases was assessed in multivariate models using logistic regression analyses.
      RESULTS: The study included 3207 patients with HS and 6412 age- and gender
      matched controls. Depression was diagnosed in 5.9% of patients with HS vs. 3.5%
      of patients without HS (P < 0.001). Anxiety was diagnosed in 3.9% of patients
      with HS vs. 2.4% of patients without HS (P < 0.001). These associations were
      significant after controlling for the confounders age and gender (Depression: OR
      = 1.7, 95% CI: 1.4-2.1; Anxiety: OR = 1.7, 95% CI: 1.3-2.1). CONCLUSIONS:
      Hidradenitis suppurativa was associated with depression and anxiety.
      Dermatologists treating patients with HS should be aware of this important
      association.

PMID- 24909647
TI  - Stacking of a stearoyl-ACP thioesterase with a dual-silenced palmitoyl-ACP
      thioesterase and ?12 fatty acid desaturase in transgenic soybean.
AB  - Soybean (Glycine max (L.) Merr) is valued for both its protein and oil, whose
      seed is composed of 40% and 20% of each component, respectively. Given its high
      percentage of polyunsaturated fatty acids, linoleic acid and linolenic acid,
      soybean oil oxidative stability is relatively poor. Historically food processors
      have employed a partial hydrogenation process to soybean oil as a means to
      improve both the oxidative stability and functionality in end-use applications.
      However, the hydrogenation process leads to the formation of trans-fats, which
      are associated with negative cardiovascular health. As a means to circumvent the
      need for the hydrogenation process, genetic approaches are being pursued to
      improve oil quality in oilseeds. In this regard, we report here on the
      introduction of the mangosteen (Garcinia mangostana) stearoyl-ACP thioesterase
      into soybean and the subsequent stacking with an event that is dual-silenced in
      palmitoyl-ACP thioesterase and ?12 fatty acid desaturase expression in a seed
      specific fashion. Phenotypic analyses on transgenic soybean expressing the
      mangosteen stearoyl-ACP thioesterase revealed increases in seed stearic acid
      levels up to 17%. The subsequent stacked with a soybean event silenced in both
      palmitoyl-ACP thioesterase and ?12 fatty acid desaturase activity, resulted in a
      seed lipid phenotype of approximately 11%-19% stearate and approximately 70%
      oleate. The oil profile created by the stack was maintained for four generations
      under greenhouse conditions and a fifth generation under a field environment.
      However, in generation six and seven under field conditions, the oleate levels
      decreased to 30%-40%, while the stearic level remained elevated. 

PMID- 24909648
TI  - Effects of gentamicin monotherapy for the initial treatment of community-onset
      complicated non-obstructive acute pyelonephritis due to Enterobacteriaceae in
      elderly and non-elderly women.
AB  - Aminoglycosides may serve as fluoroquinolone-sparing or cephalosporin-sparing
      agents if the clinical effectiveness of aminoglycoside monotherapy is
      demonstrated. The purposes of this study were to investigate the clinical
      efficacy of gentamicin as an initial empirical antimicrobial agent and to
      evaluate the effects of gentamicin resistance on clinical outcomes in women with
      complicated non-obstructive acute pyelonephritis (APN). Medical records of 1066
      women with a diagnosis of APN were reviewed retrospectively. We enrolled 275
      women with community-onset complicated non-obstructive APN due to
      Enterobacteriaceae who received gentamicin as their initial antibiotic. Of these
      275 patients, 43 had gentamicin-resistant (GM-R) Enterobacteriaceae APN, and 232
      had gentamicin-susceptible (GM-S) Enterobacteriaceae APN. The early clinical
      success rates were 67.4% (29/43) versus 89.7% (208/232) at 72 h in the GM-R
      versus the GM-S groups (p 0.001). The overall clinical cure rate was 100% (43/43)
      and 98.7% (229/232) in the GM-R and GM-S groups, respectively. The duration of
      hospital stay was significantly longer in the elderly, although there were no
      significant differences in the rates of early clinical success, final clinical
      cure, mortality, and time to fever clearance between the elderly and non-elderly
      groups. Resistance of Enterobacteriaceae to gentamicin, haematuria and serum C
      reactive protein level>=20 mg/dL were independently associated with early
      clinical failure. Gentamicin can be an effective initial antibiotic option for
      empirical therapy in women with community-onset complicated APN who do not need
      urological interventional procedures. The use of gentamicin may contribute to a
      reduction of fluoroquinolone or broad-spectrum cephalosporin use in the treatment
      of complicated APN.

PMID- 24909650
TI  - Regional analysis of drought and heat impacts on forests: current and future
      science directions.
AB  - Accurate assessments of forest response to current and future climate and human
      actions are needed at regional scales. Predicting future impacts on forests will
      require improved analysis of species-level adaptation, resilience, and
      vulnerability to mortality. Land system models can be enhanced by creating trait
      based groupings of species that better represent climate sensitivity, such as
      risk of hydraulic failure from drought. This emphasizes the need for more
      coordinated in situ and remote sensing observations to track changes in ecosystem
      function, and to improve model inputs, spatio-temporal diagnosis, and predictions
      of future conditions, including implications of actions to mitigate climate
      change. 

PMID- 24909651
TI  - Science-in-brief: What is needed to prevent tendon injury in equine athletes? A
      conversation between researchers and industry stakeholders.

PMID- 24909649
TI  - Comparison of swallowing function after intensity-modulated radiation therapy and
      conventional radiotherapy for head and neck cancer.
AB  - BACKGROUND: Intensity-modulated radiotherapy (IMRT) is hoped to protect
      structures important for swallow function. We compared posttreatment swallow
      function in 7 pairs of patients with head and neck cancer treated with either
      IMRT or conventional radiotherapy (RT). METHODS: Patients were matched on tumor
      characteristics. Swallowing function was evaluated with the modified barium
      swallow procedure pretreatment and at 3 and 6 months postcancer treatment
      completion. Swallows were analyzed for bolus transit times, bolus residues,
      laryngeal closure (LAC) duration, cricopharyngeal opening (CPO) duration, and
      oropharyngeal swallow efficiency (OPSE). Data were analyzed using multifactor
      repeated measures analysis of variance and adjusted for baseline function.
      RESULTS: Main effect of radiation type was significant for all measures on at
      least 1 bolus type. Patients treated with IMRT demonstrated shorter bolus transit
      times, less oral and pharyngeal residue, longer LAC, and larger OPSE. CONCLUSION:
      Patients treated with IMRT demonstrated faster, more efficient swallows, and
      greater airway protection.

PMID- 24909652
TI  - The use of the noninferiority analysis in clinical studies.

PMID- 24909653
TI  - Hospital biosecurity--how far have we come in the last 10 years?

PMID- 24909654
TI  - Five things equine veterinarians should know about genomics.

PMID- 24909655
TI  - 'Equine research--our only business': the Grayson-Jockey Club Research
      Foundation.

PMID- 24909656
TI  - Isolation of the sapogenin from defatted seeds of Camellia oleifera and its
      neuroprotective effects on dopaminergic neurons.
AB  - Sasanqua saponin is a major active compound in the defatted seeds of Camellia
      oleifera but is always discarded without effective utilization. The sapogenin
      from hydrolysis of sasanqua saponin was purified, and its amination derivative
      was investigated on its neuroprotective effects, which were evaluated by animal
      models of Parkinson disease in mice induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). The results showed that the sapogenin and its
      derivative increased dopamine content in striatum and tyrosine hydroxylase (TH)
      positive cells in substantia nigra and relieved inflammation and behavioral
      disorder, but the effect on movement was reversed by dopamine receptor antagonist
      haloperidol and was not intervened by adenosine receptor antagonist CGS 15943.
      Molecular simulation showed the interaction between dopamine receptor and the
      sapogenin or its derivative. It is proven that the sapogenin can protect dopamine
      neurons through antineuroinflammation and activation of dopamine receptor rather
      than adenosine receptor, and its amination improves the effects. This research
      provides the prospective prodrugs for Parkinson disease and a new medicinal
      application of sasanqua saponin. 

PMID- 24909657
TI  - Evaluating toxicity of heavy fuel oil fractions using complementary modeling and
      biomimetic extraction methods.
AB  - The toxicity of chemically dispersed heavy fuel oil (HFO) and 3 distillate
      fractions to rainbow trout (Oncorhynchus mykiss) embryos was evaluated using the
      PETROTOX model and a biomimetic extraction technique that involved passive
      sampling of oil-contaminated test media with solid-phase microextraction (SPME)
      fibers. Test solutions for toxicity testing were generated using a combination of
      dispersant and high-energy mixing. The resulting water accommodated fractions
      (WAF) provided complex exposure regimens that included both dissolved
      hydrocarbons and oil droplets. The toxicity of the various fractions differed by
      approximately 3 orders of magnitude when expressed on the basis of WAF dilution.
      Using detailed compositional data, the PETROTOX model predicted the speciation of
      hydrocarbons between dissolved and oil droplet phases and explained observed
      toxicity based on computed dissolved phase toxic units (TUs). A key finding from
      model calculations was that dissolved hydrocarbon exposures and associated TUs
      were a nonlinear function of WAF dilution, because dissolved hydrocarbons were
      largely controlled by the dissolution of oil droplets that were transferred in
      WAF dilutions. Hence, oil droplets served to "buffer" dissolved concentrations in
      WAF dilutions at loadings greater than 1 mg/L, resulting in higher dissolved
      concentrations and TUs than expected based on dilution. The TUs computed at each
      WAF dilution explained the observed toxicity among the HFO and fractions to
      within a factor of 3. Dissolved material measured by SPME showed a consistent
      relationship with model-predicted TUs, confirming the utility of this approach
      for providing an integrated measure of exposure to bioavailable hydrocarbons.
      These 2 approaches provide complementary tools for better defining
      bioavailability of complex petroleum substance.

PMID- 24909658
TI  - Oxidative demethylation of DNA and RNA mediated by non-heme iron-dependent
      dioxygenases.
AB  - DNA/RNA methylation can be generated by methyltransferases and thus plays a
      critical role in regulating cellular processes; alternatively, nucleic acid
      methylation can be produced by methylation agents and is cytotoxic/mutagenic if
      left unrepaired. Oxidative demethylation mediated by non-heme iron-dependent
      dioxygenases is an efficient way to reverse either the cellular roles of
      regulatory methylation or the cytotoxic/mutagenic effects of methylation damage.
      In this Focus Review we summarize recent advances in the study of nucleic acid
      dioxygenases exemplified by the TET and AlkB family proteins, with an emphasis on
      chemical insights from the recent literature. Comparison of the chemical
      mechanisms of these dioxygenases revealed that differences in the mechanism also
      contribute significantly to their distinct biological functions. 

PMID- 24909659
TI  - Blastic plasmacytoid dendritic cell neoplasm in a 7-year-old girl with a solitary
      skin lesion mimicking traumatic purpura.

PMID- 24909660
TI  - Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia
      progression than typical environmental risk factors.
AB  - Gout/hyperuricemia is a common multifactorial disease having typical
      environmental risks. Recently, common dysfunctional variants of ABCG2, a urate
      exporter gene also known as BCRP, are revealed to be a major cause of
      gout/hyperuricemia. Here, we compared the influence of ABCG2 dysfunction on serum
      uric acid (SUA) levels with other typical risk factors in a cohort of 5,005
      Japanese participants. ABCG2 dysfunction was observed in 53.3% of the population
      investigated, and its population-attributable risk percent (PAR%) for
      hyperuricemia was 29.2%, much higher than those of the other typical
      environmental risks, i.e. overweight/obesity (BMI >= 25.0; PAR% = 18.7%), heavy
      drinking (>196 g/week (male) or >98 g/week (female) of pure alcohol; PAR% =
      15.4%), and aging (>=60 years old; PAR% = 5.74%). SUA significantly increased as
      the ABCG2 function decreased (P = 5.99 * 10(-19)). A regression analysis revealed
      that ABCG2 dysfunction had a stronger effect than other factors; a 25% decrease
      in ABCG2 function was equivalent to "an increase of BMI by 1.97-point" or "552.1
      g/week alcohol intake as pure ethanol" in terms of ability to increase SUA.
      Therefore, ABCG2 dysfunction originating from common genetic variants has a much
      stronger impact on the progression of hyperuricemia than other familiar risks.
      Our study provides a better understanding of common genetic factors for common
      diseases.

PMID- 24909661
TI  - Sensitivity and specificity of the Eating Assessment Tool and the Volume
      Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia.
AB  - BACKGROUND: Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder
      that causes severe nutritional and respiratory complications. Our aim was to
      determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume
      Viscosity Swallow Test (V-VST) for clinical evaluation of OD. METHODS: We studied
      120 patients with swallowing difficulties and 14 healthy subjects. OD was
      evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V
      VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort
      test that uses boluses of different volumes and viscosities to identify clinical
      signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and
      residue) and impaired safety of swallow (cough, voice changes, and oxygen
      desaturation >=3%). Discriminating ability was assessed by the AUC of the ROC
      curve and sensitivity and specificity values. KEY RESULTS: According to VFS,
      prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired
      safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of
      0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity).
      The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity
      and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity
      for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations.
      CONCLUSIONS & INFERENCES: Clinical methods for screening (EAT-10) and assessment
      (V-VST) of OD offer excellent psychometric proprieties that allow adequate
      management of OD. Their universal application among at-risk populations will
      improve the identification of patients with OD at risk for malnutrition and
      aspiration pneumonia.

PMID- 24909662
TI  - No long-term clinical benefit from manual aspiration thrombectomy in ST-elevation
      myocardial infarction patients. Data from NRDES registry.
AB  - BACKGROUND: Current STEMI guidelines recommend thrombectomy should be considered
      during primary PCI. Multiple data from randomized clinical trials, registries,
      and metanalysis have confirmed the efficacy of thrombectomy in terms of surrogate
      endpoints like better myocardial perfusion, less pronounced distal embolization,
      and conflicting results on lower all-cause mortality. Our aim was to analyze long
      term outcome of STEMI patients treated with manual thrombectomy during primary
      PCI in a contemporary national registry. METHODS: There were 13 catheterization
      laboratories in Poland that enrolled patients in NRDES Registry. Patients were
      divided into two groups: those that were treated with manual thrombectomy for
      their primary PCI vs. those who were not. RESULTS: There were altogether 2,686
      patients enrolled in the NRDES Registry of whom 1,763 were diagnosed with STEMI
      (66%). Aspiration thrombectomy was used in 673 of these cases (38%) and 1,090
      (62%) patients were treated without thrombectomy during the index primary PCI.
      Overall mortality at 1 year was 11.03% in thrombectomy and 7.46% in no
      thrombectomy group respectively (P = 0.0292 which became insignificant after
      propensity score matching adjustment P = 0.613). Specific subgroup analyses
      revealed that there was no benefit from aspiration thrombectomy in neither
      subgroup. CONCLUSIONS: Manual aspiration thrombectomy in patients undergoing
      primary PCI for STEMI was not associated with improved long-term 1-year clinical
      outcome. Subgroup analysis did not reveal any specific setting in which
      thrombectomy would be clinically superior. (c) 2014 Wiley Periodicals, Inc.

PMID- 24909664
TI  - Wear of nanofilled dental composites at varying filler concentrations.
AB  - The aim of this study is to examine the effects of nanofiller concentration on
      the mechanisms of wear of a dental composite. Nanofilled composites were
      fabricated with a bisphenol A glycidyl methacrylate polymer and 40 nm SiO2 filler
      particles at three filler loads (25, 50, and 65 wt %). The elastic modulus,
      flexural strength, and hardness of the composites and the unfilled resin were
      measured. The materials (n = 8) were tested in the modified wear testing device
      at 50,000, 100,000, and 200,000 cycles with 20N force at 1 Hz. A 33% glycerine
      lubricant and stainless steel antagonist were used. The worn composite and
      antagonist surfaces were analyzed with noncontact profilometry and SEM. The
      volumetric wear data indicated that there are significant differences between
      filler concentrations and cycles (p < 0.05). A trend was noted that increasing
      filler content beyond 25% decreased the wear resistance of the composites.
      Increasing filler content increased hardness and modulus and increased flexural
      strength up to 50% fill. SEM evaluation of the worn specimens indicated that the
      resin and 25% filled materials exhibited cracking and failed by fatigue and the
      50 and 65% filled materials exhibited microcutting and failed by abrasive wear.
      Based on the results of this study, composite manufacturers are recommended to
      use a filler concentration between 25 and 50% when using nanosized filler
      particles.

PMID- 24909663
TI  - Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure.
AB  - The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure
      remain controversial. Our aim was to test whether, during an infection with Stx2
      producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium
      and thereby possibly contributes to acute renal failure. Mice represent a
      suitable model because they, like humans, express the Stx2-receptor Gb3 in the
      tubular epithelium but, in contrast to humans, not in glomerular endothelia, and
      are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice,
      Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance,
      which was most likely the cause of death. Tubule-specific depletion of Gb3
      protected the mice from acute renal failure. In vitro, Stx2 induced secretion of
      proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus
      implicating a direct effect of Stx2 on the tubular epithelium. To correlate these
      results to human disease, kidney biopsies and outcome were analysed in patients
      with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of
      kidney biopsies showed different stages of an ongoing TMA; however, no glomerular
      complement activation could be demonstrated. All biopsies, including those
      without TMA, showed severe acute tubular damage. Due to these findings, patients
      were treated with supportive therapy without complement-inhibiting antibodies
      (eculizumab) or immunoadsorption. Despite the severity of the initial disease
      [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l,
      platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all
      patients were discharged after 33 (range 19-43) days with no neurological
      symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl].
      The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months.
      Based on these data, one may surmise that acute tubular damage represents a
      separate pathophysiological mechanism, importantly contributing to Stx2-mediated
      acute kidney failure. Specifically in young adults, an excellent outcome can be
      achieved by supportive therapy only.

PMID- 24909665
TI  - Fully diastereoselective synthesis of polysubstituted, functionalized piperidines
      and decahydroquinolines based on multicomponent reactions catalyzed by cerium(IV)
      ammonium nitrate.
AB  - The cerium(IV) ammonium nitrate (CAN)-catalyzed, three-component reaction between
      primary amines, beta-dicarbonyl compounds, and alpha,beta-unsaturated aldehydes
      in ethanol heated to reflux, constitutes a general, one-pot synthesis of 1,4
      dihydropyridines. Their reduction with sodium triacetoxyborohydride furnished
      piperidine derivatives bearing up to five substituents with full
      diastereoselectivity in a hitherto inaccessible stereochemical arrangement. The
      reaction proceeded with no significant loss of enantiomeric purity under mild
      reduction conditions that are compatible with several functional groups that are
      normally sensitive to reduction. Octahydroquinolin-5-one derivatives, which were
      prepared by a modified version of the initial multicomponent reaction, were not
      suitable substrates for the sodium triacetoxyborohydride mediated reduction, but
      they were transformed into the corresponding decahydroquinolines, including a
      precursor of the amphibian alkaloid pumiliotoxin C, by catalytic hydrogenation
      under a variety of conditions. 

PMID- 24909666
TI  - Genotype-positive status in patients with hypertrophic cardiomyopathy is
      associated with higher rates of heart failure events.
AB  - BACKGROUND: The aim of the study was to clarify the relationship between genotype
      status and major cardiovascular outcomes in a large cohort of patients with
      hypertrophic cardiomyopathy. METHODS AND RESULTS: Genetic testing was performed
      in 558 consecutive proband patients with hypertrophic cardiomyopathy. Baseline
      and follow-up (mean follow-up 6.3 years) clinical and echocardiographic data were
      obtained. Pathogenic mutations were identified in 198 (35.4%) patients. Genotype
      positive patients were more likely to be women (44% versus 30%; P=0.001), younger
      (39 versus 48 years; P<0.001), and have a family history of hypertrophic
      cardiomyopathy (53% versus 20%; P<0.001), as well as family history of sudden
      cardiac death (17% versus 7%; P=0.002). There were no significant differences in
      the rates of atrial fibrillation, stroke, or septal reduction procedures.
      Multivariable analysis demonstrated that genotype-positive status was an
      independent risk factor for the development of combined heart failure end points
      (decline in left ventricular ejection fraction to <50%, New York Heart
      Association III or IV in the absence of obstruction, heart failure-related
      hospital admission, transplantation, and heart failure-related death; hazards
      ratio, 4.51; confidence interval, 2.09-9.31; P<0.001). No difference was seen in
      heart failure events between the myosin heavy chain and myosin-binding protein C
      genotype-positive patients. CONCLUSIONS: The presence of a pathogenic sarcomere
      mutation in patients with hypertrophic cardiomyopathy was associated with an
      increase in heart failure events, with no differences in event rates seen between
      myosin heavy chain and myosin-binding protein C genotype-positive patients. The
      presence of a disease-causing mutation seems more clinically relevant than the
      specific mutation itself.

PMID- 24909667
TI  - Outcome in phospholamban R14del carriers: results of a large multicentre cohort
      study.
AB  - BACKGROUND: The pathogenic phospholamban R14del mutation causes dilated and
      arrhythmogenic right ventricular cardiomyopathies and is associated with an
      increased risk of malignant ventricular arrhythmias and end-stage heart failure.
      We performed a multicentre study to evaluate mortality, cardiac disease outcome,
      and risk factors for malignant ventricular arrhythmias in a cohort of
      phospholamban R14del mutation carriers. METHODS AND RESULTS: Using the family
      tree mortality ratio method in a cohort of 403 phospholamban R14del mutation
      carriers, we found a standardized mortality ratio of 1.7 (95% confidence
      interval, 1.4-2.0) with significant excess mortality starting from the age of 25
      years. Cardiological data were available for 295 carriers. In a median follow-up
      period of 42 months, 55 (19%) individuals had a first episode of malignant
      ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The
      youngest age at which a malignant ventricular arrhythmia occurred was 20 years,
      whereas for an end-stage heart failure event this was 31 years. Independent risk
      factors for malignant ventricular arrhythmias were left ventricular ejection
      fraction <45% and sustained or nonsustained ventricular tachycardia with hazard
      ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence
      interval, 1.5-4.5), respectively. CONCLUSIONS: Phospholamban R14del mutation
      carriers are at high risk for malignant ventricular arrhythmias and end-stage
      heart failure, with left ventricular ejection fraction <45% and sustained or
      nonsustained ventricular tachycardia as independent risk factors. High mortality
      and a poor prognosis are present from late adolescence. Genetic and cardiac
      screening is, therefore, advised from adolescence onwards.

PMID- 24909668
TI  - Increased production of interleukin-17 over interleukin-10 by treg cells
      implicates inducible costimulator molecule in experimental spondyloarthritis.
AB  - OBJECTIVE: HLA-B27/human beta2 -microglobulin (hbeta2 m)-transgenic (B27
      transgenic) rats develop an inflammatory disorder resembling spondyloarthritis,
      with accumulation of proinflammatory Th17 cells. Because Treg cells and Th17
      cells have opposing effects in inflammatory disorders, we sought to determine
      whether biased expansion of Th17 cells could result from altered Treg cell
      frequency and/or function in B27-transgenic rats. METHODS: We characterized the
      phenotype and function of Treg cells from B27-transgenic rats in comparison with
      those from control rats, by examining their expression of cell surface markers,
      suppressive activity, cytokine production, and differentiation pattern. RESULTS:
      In B27-transgenic rats, the preferential accumulation of CD4+ Teff cells over
      Treg cells was not associated with a defect in Treg cell differentiation or
      suppressive activity. The expression of Treg cell markers was similar between B27
      transgenic and control rats, with the exception of the inducible costimulator
      (ICOS) molecule, which was overexpressed in B27-transgenic rats. High levels of
      ICOS are considered to be a hallmark of Treg cells with heightened suppressive
      activity and interleukin-10 (IL-10) expression. Paradoxically, the production of
      IL-10 by Treg cells was reduced in B27-transgenic rats, whereas the production of
      IL-17 was enhanced. Moreover, the addition of anti-ICOS monoclonal antibodies
      during Treg cell differentiation in the presence of dendritic cells from B27
      transgenic rats reversed this cytokine profile, restoring the balance between IL
      10 and IL-17 in Treg cells from B27-transgenic rats. CONCLUSION: We observed
      dysregulated production of IL-10 and IL-17 by Treg cells from B27-transgenic
      rats, which may contribute to disease development. Moreover, our data highlight a
      key role for ICOS signaling in the generation of imbalanced production of IL-10
      and IL-17 by Treg cells in this experimental model of spondyloarthritis.

PMID- 24909671
TI  - Physicochemical properties, antioxidant activities and protective effect against
      acute ethanol-induced hepatic injury in mice of foxtail millet (Setaria italica)
      bran oil.
AB  - This study was designed to investigate physicochemical characterization of the
      oil extracted from foxtail millet bran (FMBO), and the antioxidant and
      hepatoprotective effects against acute ethanol-induced hepatic injury in mice. GC
      MS analysis revealed that unsaturated fatty acids (UFAs) account for 83.76% of
      the total fatty acids; in particular, the linoleic acid (C18:2) is the
      predominant polyunsaturated fatty acid (PUFA), and the compounds of squalene and
      six phytosterols (or phytostanols) were identified in unsaponifiable matter of
      FMBO. The antioxidant activity examination of FMBO in vitro showed highly ferric
      reducing antioxidant power and scavenging effects against DPPH. and HO. radicals.
      Furthermore, the protective effect of FMBO against acute hepatic injuries induced
      by ethanol was verified in mice. In this, intragastric administration with
      different dosages of FMBO in mice ahead of acute ethanol administration could
      observably antagonize the ethanol-induced increases in serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and
      the hepatic malondialdehyde (MDA) levels, respectively, along with enhanced
      hepatic superoxide dismutase (SOD) levels relative to the control. Hepatic
      histological changes were also observed and confirmed that FMBO is capable of
      attenuating ethanol-induced hepatic injury.

PMID- 24909670
TI  - The protective effects of berry-derived anthocyanins against visible light
      induced damage in human retinal pigment epithelial cells.
AB  - BACKGROUND: Studies have shown that anthocyanins (ACNs) in berries contribute to
      eye health. However, information on the relationship between the chemical
      structures and visual functions of ACNs is scarce. This study investigated the
      protection effects of ACNs with different structures against visible light
      induced damage in human retinal pigment epithelial (RPE) cells. RESULTS: Four
      ACNs with different aglycones, namely, pelargonidin-3-glucoside (Pg-3-glu),
      cyanidin-3-glucoside (Cy-3-glu), delphinidin-3-glucoside, and malvidin-3
      glucoside (Mv-3-glu), were isolated from three berries (blueberry, blackberry and
      strawberry). Of these ACNs, Cy-3-glu exhibited the highest reactive oxygen
      species inhibitory capacity in RPE cells, with 40 ug mL(-1) Cy-3-glu showing a
      ROS clearance of 57.5% +/- 4.2%. The expression of vascular endothelial growth
      factor levels were significantly (P < 0.05) down-regulated by Cy-3-glu and Mv-3
      glu in a visible light-induced damage RPE cell model. Cy-3-glu and Pg-3-glu
      treatments significantly (P < 0.05) inhibited the increase in beta-galactosidase
      during the RPE cell ageing caused by visible light exposure. CONCLUSION: Our
      findings suggest that the biological properties of different ACNs significantly
      vary. Cy-3-glu, which contains an ortho hydroxyl group in its B ring, possibly
      exerts multiple protective effects (antioxidant, anti-angiogenic and anti-ageing)
      in RPE cells. Therefore, Cy-3-glu may prove useful as a prophylactic health food
      for the prevention of retinal diseases.

PMID- 24909672
TI  - Site-specific fluorescence labelling of RNA using bio-orthogonal reaction of
      trans-cyclooctene and tetrazine.
AB  - This communication describes a general approach for site-specific fluorescence
      labelling of RNA using a cytidine triphosphate (CTP) analogue derivatized with a
      trans-cyclooctene group. The analogue was efficiently incorporated into a model
      RNA strand using in vitro transcription. Bio-orthogonal reaction with fluorescein
      labelled tetrazine was utilized to fluorescently tag the synthetic RNA strand. 

PMID- 24909673
TI  - Requirement of AMPA receptor stimulation for the sustained antidepressant
      activity of ketamine and LY341495 during the forced swim test in rats.
AB  - Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, and group
      II metabotropic glutamate (mGlu2/3) receptor antagonists produce antidepressant
      effects in animal models of depression, which last for at least 24h, through the
      transient increase in glutamate release, leading to activation of the alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor. Both ketamine and an
      mGlu2/3 receptor antagonist reportedly increase the expression of GluR1, an AMPA
      receptor subunit, within 24h, which may account for the sustained enhancement of
      excitatory synaptic transmission following ketamine administration. However,
      whether the sustained increase in AMPA receptor-mediated synaptic transmission is
      associated with the antidepressant effects of ketamine and mGlu2/3 receptor
      antagonists has not yet been investigated. In the present study, to address this
      question, we tested whether AMPA receptor stimulation at 24h after a single
      injection of ketamine or an mGlu2/3 receptor antagonist, (2S)-2-amino-2-[(1S,2S)
      2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495) was necessary
      for the antidepressant effect of these compounds using a forced swim test in
      rats. A single injection of ketamine or LY341495 at 24h before the test
      significantly decreased the immobility time. An AMPA receptor antagonist, 2,3
      dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX),
      administered 30min prior to the test significantly and dose-dependently reversed
      the antidepressant effects of ketamine and LY341495, while NBQX itself had no
      effect on the immobility time. Our findings suggest that AMPA receptor
      stimulation at 24h after a single injection of ketamine or LY341495 is required
      to produce the anti-immobility effects of these compounds. Moreover, the present
      results provide additional evidence that an mGlu2/3 receptor antagonist may share
      some of neural mechanisms with ketamine to exert antidepressant effects.

PMID- 24909674
TI  - Comparative genotoxicity of nanosilver in human liver HepG2 and colon Caco2 cells
      evaluated by fluorescent microscopy of cytochalasin B-blocked micronucleus
      formation.
AB  - As a consequence of the increased use of silver nanoparticles in food, food
      contact materials, dietary supplements and cosmetics to prevent fungal and
      bacterial growth, there is a need for validated rapid screening methods to assess
      the safety of nanoparticle exposure. This study evaluated two widely used in
      vitro cell culture models, human liver HepG2 cells and human colon Caco2 cells,
      as tools for assessing the potential genotoxicity of 20-nm nanosilver. The
      average silver nanoparticle size as determined by transmission electron
      microscopy (TEM) was 20.4 nm. Dynamic light scattering (DLS) analysis showed no
      large agglomeration of the silver nanoparticles. The silver concentration in a 20
      nm nanosilver solution determined by the inductively coupled plasma-mass
      spectrometry (ICP-MS) analysis was 0.962 mg ml(-1) . Analysis by ICP-MS and TEM
      demonstrated the uptake of 20-nm silver by both HepG2 and Caco2 cells.
      Genotoxicity was determined by the cytochalasin B-blocked micronucleus assay with
      acridine orange staining and fluorescence microscopy. Concentration- and time
      dependent increases in the frequency of binucleated cells with micronuclei
      induced by the nanosilver was observed in the concentration range of 0.5 to 15 ug
      ml(-1) in both HepG2 and Caco2 cells compared with the control. Our results
      indicated that HepG2 cells were more sensitive than Caco2 cells in terms of
      micronuclei formation induced by nanosilver exposure. In summary, the results of
      this study indicate that the widely used in vitro models, HepG2 and Caco2 cells
      in culture, represent potential screening models for prediction of genotoxicity
      of silver nanoparticles by in vitro micronucleus assay.

PMID- 24909676
TI  - Unlocking nature's C-H bonds.
AB  - In an idealistic setting, it can be imagined that if every CH bond on an organic
      molecule could be selectively functionalized, the fields of chemical synthesis
      and drug discovery would be forever revolutionized. With the purpose of
      investigating the practicality of this idealistic scenario, our group has
      endeavored to unlock the potential of nature's CH bonds by developing palladium
      catalyzed, site selective CH insertions that can be incorporated into both known
      and new catalytic cycles. To this end, we have developed a number of catalytic
      transformations that not only provide rapid diversification of simple starting
      materials and natural products through CH functionalization, but streamline the
      synthesis of a variety of natural products with biological activity and expand
      upon methods to access highly valuable enantiopure materials. 

PMID- 24909675
TI  - mTOR inhibition and levels of the DNA repair protein MGMT in T98G glioblastoma
      cells.
AB  - BACKGROUND: Glioblastoma multiforme (GBM), the most common and most aggressive
      type of primary adult brain tumour, responds poorly to conventional treatment.
      Temozolomide (TMZ) chemotherapy remains the most commonly used treatment, despite
      a large proportion of tumours displaying TMZ resistance. 60% of GBM tumours have
      unmethylated MGMT promoter regions, resulting in an overexpression of the DNA
      repair protein O6-methylguanine-DNA methyltransferase (MGMT), which is
      responsible for tumour resistance to TMZ chemotherapy. Tumours also often exhibit
      hyperactive PI3-kinase/mTOR signalling, which enables them to resynthesise
      proteins quickly. Since MGMT is a suicide protein that is degraded upon binding
      to and repairing TMZ-induced O6-methylguanine adducts, it has been hypothesized
      that inhibition of translation via the mTOR signalling pathway could generate a
      tumour-specific reduction in MGMT protein and increase TMZ sensitivity. METHODS:
      MGMT was monitored at the post-transcriptional, translational and protein levels,
      to determine what effect mTOR inhibition was having on MGMT protein expression in
      vitro. RESULTS: We show that inhibiting mTOR signalling is indeed associated with
      acute inhibition of protein synthesis. Western blots show that despite this,
      relative to loading control proteins, steady state levels of MGMT protein
      increased and MGMT mRNA was retained in heavy polysomes. Whilst TMZ treatment
      resulted in maintained MGMT protein levels, concomitant treatment of T98G cells
      with TMZ and KU0063794 resulted in increased MGMT protein levels without changes
      in total mRNA levels. CONCLUSIONS: These in vitro data suggest that,
      counterintuitively, mTOR inhibition may not be a useful adjunct to TMZ therapy
      and that more investigation is needed before applying mTOR inhibitors in a
      clinical setting.

PMID- 24909677
TI  - Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as
      CC-chemokine receptor 4 (CCR4) antagonists.
AB  - A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of
      commercially available aryl amines was synthesised and screened as human CCR4
      antagonists, in order to identify a suitable hit for the start of a lead
      optimisation programme. Hits were required to be more potent than an existing
      indazole series, have better physicochemical properties (clogP <3.5, chrom
      logD7.4 <5.3 and CLND solubility >116 MUg/mL), and be stable to acid and light.
      The benzimidazol-2-one core was identified as a hit suitable for further
      investigation. Substitution at N1 with small alkyl groups was tolerated; however,
      these analogues were inactive in the whole blood assay (pA2 <5).
      Azabenzimidazolone analogues were all found to be active, with compound 38
      exhibiting whole blood activity of 6.1, low molecular weight (389) and chrom
      logD7.4 (2.4), high LE (0.43), and solubility (152 MUg/mL). In addition, 38 had
      human serum albumin binding of around 93% and met all the criteria for
      progression to lead optimisation.

PMID- 24909678
TI  - Synthesis, biological evaluation and molecular modeling of 1,3,4-thiadiazol-2
      amide derivatives as novel antitubulin agents.
AB  - A series of 1,3,4-thiadiazol-2-amide derivatives (6a-w) were designed and
      synthesized as potential inhibitors of tubulin polymerization and as anticancer
      agents. The in vitro anticancer activities of these compounds were evaluated
      against three cancer cell lines by the MTT method. Among all the designed
      compounds, compound 6f exhibited the most potent anticancer activity against
      A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03 MUM, 0.06 MUM
      and 0.05 MUM, respectively. Compound 6f also exhibited significant tubulin
      polymerization inhibitory activity (IC50=1.73 MUM), which was superior to the
      positive control. The obtained results, along with a 3D-QSAR study and molecular
      docking that were used for investigating the probable binding mode, could provide
      an important basis for further optimization of compound 6f as a novel anticancer
      agent.

PMID- 24909679
TI  - Target evaluation of deoxyhypusine synthase from Theileria parva the neglected
      animal parasite and its relationship to Plasmodium.
AB  - East Coast fever (ECF) is a tick-borne disease caused by the parasite Theileria
      parva which infects cattle. In Sub-Saharan Africa it leads to enormous economic
      costs. After a bite of a tick, sporozoites invade the host lymphocytes and
      develop into schizonts. At this stage the parasite transforms host lymphocytes
      resulting in the clonal expansion of infected lymphocytes. Animals develop a
      lymphoma like disorder after infection which is rapidly fatal. Hitherto, a few
      drugs of the quinone type can cure the disease. However, therapy can only be
      successful after early diagnosis. The genera Theileria and Plasmodium, which
      includes the causative agent of human malaria, are closely related apicomplexan
      parasites. Enzymes of the hypusine pathway, a posttranslational modification in
      eukaryotic initiation factor EIF-5A, have shown to be druggable targets in
      Plasmodium. We identified the first enzyme of the hypusine pathway from T. parva,
      the deoxyhypusine synthase (DHS), which is located on chromosome 2 of the Muguga
      strain. Transcription is significantly increased in schizonts. The expressed T.
      parva DHS reveals an open reading frame (ORF) of 370 amino acids after expression
      in Escherichia coli Rosetta cells with a molecular size of 41.26 kDa and a
      theoretical pI of 5.26. Screening of the Malaria Box which consists of 400 active
      compounds resulted in a novel heterocyclic compound with a guanyl spacer which
      reduced the activity of T. parva DHS to 45%. In sum, the guanyl residue seems to
      be an important lead structure for inhibition of Theileria DHS. Currently, more
      different guanyl analogues from the Malaria Box are tested in inhibitor
      experiments to determine their efficacy.

PMID- 24909680
TI  - Synthesis and SAR studies of benzyl ether derivatives as potent orally active
      S1P1 agonists.
AB  - We report herein the synthesis and structure-activity relationships (SAR) of a
      series of benzyl ether compounds as an S1P1 receptor modulator. From our SAR
      studies, the installation of substituents onto the central benzene ring of 2a was
      revealed to potently influence the S1P1 and S1P3 agonistic activities, in
      particular, an ethyl group on the 2-position afforded satisfactory S1P1/S1P3
      selectivity. These changes of the S1P1 and S1P3 agonistic activities caused by
      the alteration of substituents on the 2-position were reasonably explained by a
      docking study using an S1P1 X-ray crystal structure and S1P3 homology modeling.
      We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy
      along with acceptable S1P1/S1P3 selectivity, and confirmed that these compounds
      had less in vivo bradycardia risk through the evaluation of heart rate change
      after oral administration of the compounds (30 mg/kg, p.o.) in rats.

PMID- 24909681
TI  - Mechatronic DNA devices driven by a G-quadruplex-binding platinum ligand.
AB  - Contractile duplexes are DNA double helices that incorporate two strategically
      placed patches of guanine-guanine (G.G) base mismatches. Such duplexes are cation
      driven mechatronic devices, able to toggle between states with distinct
      mechanical and charge conduction properties. In aqueous lithium chloride solution
      contractile duplexes have an extended (E) and poorly conductive conformation;
      however, potassium ions drive them to a relatively conductive and structurally
      contracted (C) conformation, via intramolecular G-quadruplex formation. Here, we
      report that even in the absence of K(+) ions, a known G-quadruplex binding
      ligand, Pt-PIP [phenylphenanthroimidazole ethylenediamine platinum(II)]
      efficiently promotes the E->C transition, while a poor binder, Pt-bpy [bipyridine
      ethylenediamine platinum(II)], does not promote this transition. An examination
      of E->C transitions within two different designs for DNA contractile helices
      found an unexpected complexity: the formation of distinct C states, both
      electrically conductive, but possessing dissimilar DNA topologies. Ligand-driven
      DNA mechatronic devices such as these may constitute prototypes for electronic
      biosensors that identify G-quadruplex binding ligands. 

PMID- 24909682
TI  - Efficient solvent-free dissipative particle dynamics for lipid bilayers.
AB  - We rigorously derived effective potentials for solvent-free DPD simulation of
      lipid bilayers. The derivation relies on an earlier developed hybrid
      particle/field method and is based on the idea that the solvent is always in
      local equilibrium on a coarse-grained time scale, given the instantaneous
      templates set by the self-assembly structure. By relating the parameters in the
      effective implicit-solvent potentials directly to the lipid-solvent interactions
      and membrane properties for the explicit solvent DPD model, we constitute an
      efficient and general procedure for reformulating any DPD membrane model in an
      implicit-solvent form. Here, we determined these membrane properties for two
      existing DPD models, via an analysis of membrane fluctuation spectra. Equivalent
      single-processor implicit- and explicit-solvent calculations show the trade-mark
      of implicit solvent simulation: a 20-fold reduction of the total simulation time
      for a system containing 92% solvent. This increased efficiency enabled us to
      realistically simulate the spontaneous formation of a ~20 nm diameter vesicle on
      a single processor overnight. We believe that this work will contribute to an
      enhanced computational study of large vesicles and thus a better understanding of
      experimental liposome dynamics. 

PMID- 24909684
TI  - Safety and efficacy of melatonin in pediatric migraine prophylaxis.
AB  - OBJECTIVE: Preventive therapy in migraine must be started with frequent or
      disabling headaches in children, while, no drugs have been approved for migraine
      preventive therapy of them up to now. The aim of the present research was to
      investigate safety and efficacy of melatonin in pediatric migraine prophylaxis.
      METHODS: In a quasi- experimental study, monthly frequency, severity and duration
      of headache, migraine disability and clinical side effects in sixty migraineur
      referred children to Pediatric Neurology Clinic of Shahid Sadoughi Medical
      Sciences University, Yazd, Iran from January to June 2013 whom were treated with
      single dose of 0.3 mg/kg melatonin for three months, were evaluated. RESULTS:
      Thirty two (53.3%) girls and 28(46.7%) boys with mean age of 10.31 +/- 2.39 years
      were evaluated, 38 of whom (63.3%) had migraine without aura. Clinical adverse
      events were seen in 23.3% (N=14) of children including sleepiness in seven,
      vomiting in four, mild hypotension in two and constipation in one child.
      Excessive daytime sleepiness as a serious side effect was seen in three children
      which caused the drug use to be stopped. Monthly frequency, severity and duration
      of headache reduced from 15.63 +/- 7.64 to 7.07 +/- 4.42 attacks, from 6.20 +/-
      1.67 to 3.55 +/- 2.11 scores, and from 2.26 +/- 1.34 to 1.11 +/- 0.55 hours,
      respectively. Pediatric Migraine Disability Assessment score decreased from 31.72
      +/- 8.82 to 17.78 +/- 10.64. (All p < 0.05). CONCLUSION: Melatonin might be
      considered as an effective and without life-threatening side effects drug in
      prophylaxis of migraine in children.

PMID- 24909683
TI  - Gastric bezoar complication of Duodopa((r)) therapy in Parkinson's disease,
      treated with Coca-Cola((r)).

PMID- 24909685
TI  - Atomic resolution crystal structure of VcLMWPTP-1 from Vibrio cholerae O395:
      insights into a novel mode of dimerization in the low molecular weight protein
      tyrosine phosphatase family.
AB  - Low molecular weight protein tyrosine phosphatase (LMWPTP) is a group of
      phosphotyrosine phosphatase ubiquitously found in a wide range of organisms
      ranging from bacteria to mammals. Dimerization in the LMWPTP family has been
      reported earlier which follows a common mechanism involving active site residues
      leading to an enzymatically inactive species. Here we report a novel form of
      dimerization in a LMWPTP from Vibrio cholera 0395 (VcLMWPTP-1). Studies in
      solution reveal the existence of the dimer in solution while kinetic study
      depicts the active form of the enzyme. This indicates that the mode of
      dimerization in VcLMWPTP-1 is different from others where active site residues
      are not involved in the process. A high resolution (1.45A) crystal structure of
      VcLMWPTP-1 confirms a different mode of dimerization where the active site is
      catalytically accessible as evident by a tightly bound substrate mimicking
      ligand, MOPS at the active site pocket. Although being a member of a prokaryotic
      protein family, VcLMWPTP-1 structure resembles very closely to LMWPTP from a
      eukaryote, Entamoeba histolytica. It also delineates the diverse surface
      properties around the active site of the enzyme. 

PMID- 24909687
TI  - A novel bHLH transcription factor PebHLH35 from Populus euphratica confers
      drought tolerance through regulating stomatal development, photosynthesis and
      growth in Arabidopsis.
AB  - Plant basic helix-loop-helix (bHLH) transcription factors (TFs) are involved in a
      variety of physiological processes including the regulation of plant responses to
      various abiotic stresses. However, few drought-responsive bHLH family members in
      Populus have been reported. In this study, a novel bHLH gene (PebHLH35) was
      cloned from Populus euphratica. Expression analysis in P. euphratica revealed
      that PebHLH35 was induced by drought and abscisic acid. Subcellular localization
      studies using a PebHLH35-GFP fusion showed that the protein was localized to the
      nucleus. Ectopic overexpression of PebHLH35 in Arabidopsis resulted in a longer
      primary root, more leaves, and a greater leaf area under well-watered conditions
      compared with vector control plants. Notably, PebHLH35 overexpression lines
      showed enhanced tolerance to water-deficit stress. This finding was supported by
      anatomical and physiological analyses, which revealed a reduced stomatal density,
      stomatal aperture, transpiration rate, and water loss, and a higher chlorophyll
      content and photosynthetic rate. Our results suggest that PebHLH35 functions as a
      positive regulator of drought stress responses by regulating stomatal density,
      stomatal aperture, photosynthesis and growth. 

PMID- 24909686
TI  - Involvement of transcription factor XBP1s in the resistance of HDAC6 inhibitor
      Tubastatin A to superoxidation via acetylation-mediated proteasomal degradation.
AB  - HDAC6 is a major cytoplasmic deacetylase. XBP1s is a basic-region leucine zipper
      (bZIP) transcriptional factor. Despite their mutual involvement in the anti
      oxidative process, there are no reports about their inter-protein interactions so
      far. Here we identified a direct link between HDAC6 inhibition and XBP1s
      transcription activity in anti-oxidative damage. We showed that the specific
      HDAC6 inhibitor Tubastatin A could up-regulate XBP1s transcriptional activity,
      thereby increasing anti-oxidative genes expression. Moreover, knock down of XBP1s
      could significantly abolish the cell growth protection afforded by Tubastatin A.
      We hypothesize that Tubastatin A acts to increase XBP1s protein levels that are
      dependent on its HDAC6 deacetylase inhibition via a mechanism involving
      acetylation-mediated proteasomal degradation, providing novel mechanistic insight
      into the anti-oxidative effects of HDAC6 inhibition. 

PMID- 24909688
TI  - Cadmium induces vascular permeability via activation of the p38 MAPK pathway.
AB  - The vasculature of various organs is a targeted by the environmental toxin,
      cadmium (Cd). However, mechanisms leading to pathological conditions are poorly
      understood. In the present study, we examined the effect of cadmium chloride
      (CdCl2) on human umbilical vein endothelial cells (HUVECs). At 4 MUM, CdCl2
      induced a hyper-permeability defect in HUVECs, but not the inhibition of cell
      growth up to 24h. This effect of CdCl2 was dependent on the activation of the p38
      mitogen-activated protein kinase (MAPK) pathway. The p38 MAPK inhibitor SB203850
      suppressed the CdCl2-induced alteration in trans-endothelial electrical
      resistance in HUVEC monolayers, a model measurement of vascular endothelial
      barrier integrity. SB203850 also inhibited the Cd-induced membrane dissociation
      of vascular endothelial (VE) cadherin and beta-catenin, the important components
      of the adherens junctional complex. In addition, SB203850 reduces the Cd-induced
      expression and secretion of tumor necrosis factor alpha (TNF-alpha). Taken
      together, our findings suggest that Cd induces vascular hyper-permeability and
      disruption of endothelial barrier integrity through stimulation of p38 MAPK
      signaling.

PMID- 24909689
TI  - E2F1-regulated DROSHA promotes miR-630 biosynthesis in cisplatin-exposed cancer
      cells.
AB  - DNA damage may regulate microRNA (miRNA) biosynthesis at the levels of miRNA
      transcription, processing and maturation. Although involvement of E2F1 in the
      regulation of miRNA gene activation in response to DNA damage has been
      documented, little is known about the role of E2F1 in miRNA processing. In this
      study we demonstrate that E2F1 enhances miR-630 biosynthesis under cisplatin
      (CIS) exposure through promoting DROSHA-mediated pri-miR-630 processing. Northern
      blot and RT-qPCR revealed that CIS exposure caused not only an increase in pri
      miR-630 but also much more increase in pre-miR-630 and mature miR-630. The
      increases in pri-miR-630 and pre-miR-630 expression in unmatched proportion
      indicated that primary transcript processing was involved in CIS-stimulated miR
      630 biosynthesis. Furthermore, combination of reporter enzyme assay with mutation
      and over-expression of E2F1 showed that induction of DROSHA promoted miR-630
      expression, in which CIS-induced E2F1 activated DROSHA gene expression by
      recognizing and binding two E2F1 sites at the positions -214/-207 and -167/-160
      of the DROSHA promoter. The increased binding of E2F1 to the DROSHA promoter in
      CIS-exposed cells was further evidenced by chromatin immunoprecipitation assay.
      Together, E2F1-regulated DROSHA promotes pri-miR-630 processing, thereby,
      contributes to CIS-stimulated miR-630 expression. The involvement of E2F1
      dependent DROSHA activation in pri-miRNA processing under DNA damage stress will
      provide further insight into the regulation of miRNA biosynthesis. These data
      also give us a deeper understanding of E2F1 role in response to DNA damage. 

PMID- 24909691
TI  - C-FLIP(L) contributes to TRAIL resistance in HER2-positive breast cancer.
AB  - Breast cancers with HER2 amplification have a poorer prognosis than the luminal
      phenotypes. TRAIL activates apoptosis upon binding its receptors in some but not
      all breast cancer cell lines. Herein, we investigated the expression pattern of c
      FLIP(L) in a cohort of 251 invasive breast cancer tissues and explored its
      potential role in TRAIL resistance. C-FLIP(L) was relatively high-expressed in
      HER2-positive breast cancer in comparison with other molecular subtypes, co
      expressed with TRAIL death receptors, and inversely correlated with the apoptosis
      index. Downregulation of c-FLIP(L) sensitized SKBR3 cells to TRAIL-induced
      apoptosis in a concentration- and time-dependent manner and enhanced the
      activities and cleavages of caspase-8 and caspase-3, without altering the surface
      expression of death receptors. Together, our results indicate that c-FLIP(L)
      promotes TRAIL resistance and inhibits caspase-3 and caspase-8 activation in HER2
      positive breast cancer. 

PMID- 24909690
TI  - Significance of glycosylation in Notch signaling.
AB  - Notch signaling is essential for cell-fate specification in metazoans, and
      dysregulation of the pathway leads to a variety of human diseases including heart
      and vascular defects as well as cancer. Glycosylation of the Notch extracellular
      domain has emerged as an elegant means for regulating Notch activity, especially
      since the discovery that Fringe is a glycosyltransferase that modifies O-fucose
      in 2000. Since then, several other O-glycans on the extracellular domain have
      been demonstrated to modulate Notch activity. Here we will describe recent
      results on the molecular mechanisms by which Fringe modulates Notch activity,
      summarize recent work on how O-glucose, O-GlcNAc, and O-GalNAc glycans affect
      Notch, and discuss several human genetic disorders resulting from defects in
      Notch glycosylation. 

PMID- 24909692
TI  - Purification, cellular levels, and functional domains of lipase maturation factor
      1.
AB  - Over a third of the US adult population has hypertriglyceridemia, resulting in an
      increased risk of atherosclerosis, pancreatitis, and metabolic syndrome.
      Lipoprotein lipase (LPL), a dimeric enzyme, is the main lipase responsible for TG
      clearance from the blood after food intake. LPL requires an endoplasmic reticulum
      (ER)-resident, transmembrane protein known as lipase maturation factor 1 (LMF1)
      for secretion and enzymatic activity. LMF1 is believed to act as a client
      specific chaperone for dimeric lipases, but the precise mechanism by which LMF1
      functions is not understood. Here, we examine which domains of LMF1 contribute to
      dimeric lipase maturation by assessing the function of truncation variants. N
      terminal truncations of LMF1 show that all the domains are necessary for LPL
      maturation. Fluorescence microscopy and protease protection assays confirmed that
      these variants were properly oriented in the ER. We measured cellular levels of
      LMF1 and found that it is expressed at low levels and each molecule of LMF1
      promotes the maturation of 50 or more molecules of LPL. Thus we provide evidence
      for the critical role of the N-terminus of LMF1 for the maturation of LPL and
      relevant ratio of chaperone to substrate. 

PMID- 24909693
TI  - Interaction of 70-kDa heat shock protein with glycosaminoglycans and acidic
      glycopolymers.
AB  - Interaction of Hsp70 with natural and artificial acidic glycans is demonstrated
      based on the native PAGE analysis. Hsp70 interacts with acidic glycopolymers that
      contain clustered sulfated and di-sialylated glycan moieties on a polyacrylamide
      backbone, but not with neutral or mono-sialylated glycopolymers. Hsp70 also
      interacts and forms a large complex with heparin, heparan sulfate, and dermatan
      sulfate that commonly contain 2-O-sulfated iduronic acid residues, but not with
      other types of glycosaminoglycans (GAGs). Hsp70 consists of the N-terminal ATPase
      domain and the C-terminal peptide-binding domain. The interaction analyses using
      the recombinant N- and C-terminal half domains show that the ATPase domain
      mediates the direct interaction with acidic glycans, while the peptide-binding
      domain stabilizes the large complexes with particular GAGs. To our knowledge,
      this is the first demonstration of direct binding of Hsp70 to the particular
      GAGs. This property may be involved in the physiological functions of Hsp70 at
      the plasma membrane and extracellular environments. 

PMID- 24909695
TI  - Supramolecular luminescent lanthanide dimers for fluoride sequestering and
      sensing.
AB  - Lanthanide complexes (Ln=Eu, Tb, and Yb) that are based on a C2 -symmetric cyclen
      scaffold were prepared and characterized. The addition of fluoride anions to
      aqueous solutions of the complexes resulted in the formation of dinuclear
      supramolecular compounds in which the anion is confined into the cavity that is
      formed by the two complexes. The supramolecular assembly process was monitored by
      UV/Vis absorption, luminescence, and NMR spectroscopy and high-resolution mass
      spectrometry. The X-ray crystal structure of the europium dimer revealed that the
      architecture of the scaffold is stabilized by synergistic effects of the Eu?F?Eu
      bridging motive, pi stacking interactions, and a four-component hydrogen-bonding
      network, which control the assembly of the two [EuL] entities around the fluoride
      ion. The strong association in water allowed for the luminescence sensing of
      fluoride down to a detection limit of 24 nM. 

PMID- 24909694
TI  - A new method for multilayered, site-directed immobilization of antibody on
      polystyrene surface.
AB  - Polystyrene is a common substrate material for protein adsorption in biosensors
      and bioassays. Here, we present a new method for multilayered, site-directed
      immobilization of antibody on polystyrene surface through the linkage of a
      genetically engineered ligand and the assembly of staphylococcal protein A (SPA)
      with immunoglobulin G (IgG). In this method, antibodies were stacked on
      polystyrene surface layer by layer in a potential three-dimensional way and
      exposed the analyte-binding sites well. Enzyme-linked immunosorbent assay (ELISA)
      revealed that the new method showed a 32-fold higher detection sensitivity
      compared with the conventional one. Pull-down assay and Western blot analysis
      further confirmed that it is different from the ones of monolayer adsorption
      according to the comparison of adsorption capacity. The differentiated
      introduction of functional ligands, which is the key of this method, might offer
      a unique idea as a way to interfere with the dynamic behavior of a protein
      complex during the process of adsorption. 

PMID- 24909697
TI  - Congenital aural atresia and stenosis: surgery strategies and long-term results.
AB  - OBJECTIVE: To compare the patients who underwent surgery for congenital aural
      atresia (CAA) with congenital aural stenosis (CAS) for the stability of hearing
      results and complications during long-term follow-up. DESIGN: Retrospective
      review. STUDY SAMPLE: Seventy-five CAA patients and fifty CAS patients who
      underwent congenital meatoplasty with canalplasty and tympanoplasty between 2007
      and 2012. RESULTS: Paired comparison analyses detected no significant difference
      in preoperative ABG but significant changes in postoperative ABG, DeltaABG, the
      number of ABG < 30 dB and ABG < 10 dB between CAA and CAS. Complications such as
      postoperative stenosis, bony regrowth, external aural canal (EAC) infection, EAC
      eczema, total deaf, and lateralization of the tympanic membrane (TM) were
      observed in 61.3% of patients with CAA and 20% of patients with CAS. Chi square
      test detected significant differences in complications between patients with CAA
      and CAS (chi(2) = 20.73, p < 0.01). CONCLUSION: Meatoplasty with canalplasty and
      tympanoplasty in individuals with CAS can yield reliable and lasting positive
      hearing results with a low incidence of severe complications. The existence and
      preoperative condition of patients' TM and EAC skin helped improve hearing
      results and decrease the incidence of complications. However, the final hearing
      results and complications required stricter indications for CAA patients.

PMID- 24909696
TI  - WFS1 mutations in hearing-impaired children.
AB  - OBJECTIVE: Mutations in the WFS1 gene can cause Wolfram syndrome or nonsyndromic
      hearing impairment (HI). The objective of this study was to ascertain the
      presence of mutations in WFS1 among children with HI from unknown causes. DESIGN:
      We screened 105 Finnish children with HI for mutations in exon 8 in WFS1. STUDY
      SAMPLE: Children were born in a defined area in Northern Finland and they had
      sensorineural, mild to profound, syndromic, or nonsyndromic HI. They were
      negative for GJB2 mutations and for the m.1555A> G and m.3243A> G mutations in
      mitochondrial DNA. RESULTS: We found three rare variants and the novel
      p.Gly831Ser variant in WFS1. Segregation analysis suggested that the novel
      variant had arisen de novo. The p.Gly831Ser variant may be a new member to the
      group of heterozygous WFS1 mutations that lead to HI, while the pathogenicity of
      the rare variant p.Gly674Arg remained unclear. The other two rare variants,
      p.Glu385Lys and p.Glu776Val, did not segregate with HI in the families.
      CONCLUSIONS: WFS1 gene mutations are a rare cause of HI among Finnish children
      with HI.

PMID- 24909698
TI  - Reflections after the Diane affair.
AB  - The Pharmacovigilance Centre Lareb received 621 reports of possible adverse drugs
      reactions on Diane-35(r) . Of all reports, 388 were received after media
      attention. Of the 309 reports of thromboembolic adverse drugs reactions, 18 cases
      were fatal. In 31 cases the thromboembolic adverse drugs reaction was initially
      not recognized as such. The analysis and the turmoil of the 'Diane affair' gave
      rise to the following reflections: Reflection 1. Continuous awareness and
      attention of risk of medicines is needed, also for known risks, for timely
      recognition of adverse drugs reactions. Reflection 2. Reporting side effects
      should be part of the professional attitude. Reports play a pivotal role in the
      detection of new adverse drugs reactions and the conditions under which known
      adverse drugs reactions occur. Reflection 3. Improvement of adequate use of
      drugs. Pharmacovigilance not only has the aim to improve knowledge on risk of
      medicines, but also the aim of getting this knowledge into Health Care practice.

PMID- 24909699
TI  - Surgical repair of a congenital sternal cleft in a cat.
AB  - OBJECTIVE: To describe the clinical findings, diagnosis, and treatment of an
      incomplete cleft of the 5th-8th sternebra and a cranioventral abdominal wall
      hernia in a 2 month old Ragdoll kitten and to evaluate the short- and long-term
      outcome. STUDY DESIGN: Clinical report. ANIMALS: Ragdoll cat (n = 1), 2 months
      old. METHODS: Sternal cleft was confirmed by thoracic radiographs. Computed
      tomography (CT) was used to plan an optimal surgical approach. A ventral median
      incision was made, starting at the 3rd sternebra and extended into the abdomen.
      Ostectomy of the proximal part of the 5th left sternebra was performed. Lateral
      periosteal flaps were created, unfolded, and absorbable monofilament sutures
      preplaced to facilitate closure and the repair was reinforced by 2 peristernal
      sutures. A bone graft was applied, and the free margin of the omentum was sutured
      to the cranial aspect of the wound. RESULTS: No major complications occurred. At
      3 weeks, CT scan confirmed approximation of the hemisternebrae and at 10 months,
      complete fusion of the hemisternebrae had not occurred, but a strong connection
      of the sternal bars was present. CONCLUSION: Sternal cleft is a rare congenital
      abnormality that can be corrected surgically with favorable outcome.

PMID- 24909700
TI  - Barriers to protocol-led early discharge of low-risk febrile neutropenia
      patients.

PMID- 24909701
TI  - Febrile neutropaenia and chemotherapy discontinuation in women aged 70 years or
      older receiving adjuvant chemotherapy for early breast cancer.
AB  - AIMS: Low rates of adjuvant chemotherapy use are frequently reported in older
      women with early breast cancer. One of the reasons for this may be the risk of
      febrile neutropaenia or the perception that older patients will probably not
      complete the chemotherapy course prescribed. There are no data regarding these
      adverse outcomes in routine clinical practice. PATIENTS AND METHODS: We
      identified 128 patients aged 70 years or over who received neoadjuvant or
      adjuvant chemotherapy for early breast cancer in seven UK cancer centres between
      2006 and 2012. Data were collected regarding standard clinical and pathological
      variables and treatment toxicity and outcomes. RESULTS: Twenty-four patients
      (19%) had an episode of febrile neutropaenia. Overall, 27 patients (21%) did not
      complete their planned therapy. Chemotherapy discontinuation was more common in
      those patients with an episode of febrile neutropaenia (46% versus 16%, P =
      0.004). Thirty patients (23%) were admitted with chemotherapy-related
      complications. There were no treatment-related deaths. CONCLUSIONS: The rates of
      febrile neutropaenia and treatment discontinuation are high in women aged 70
      years or over receiving adjuvant chemotherapy for breast cancer. Close attention
      should be paid to the choice or regimen and the use of supportive therapies in
      this patient population.

PMID- 24909702
TI  - Bevacizumab in non-small cell lung cancer: an overview of practice in the era of
      molecular testing.
AB  - The place of bevacizumab in the management of advanced non-small cell lung cancer
      (NSCLC) was reviewed. Particular reference has been made to the recent research
      on the systemic treatment of NSCLC indicating that treatment tailored to
      specifically identified morphology or genetic profile has recently changed
      practice. The result of this recent research means that bevacizumab has little,
      if any, place in the treatment of NSCLC. 

PMID- 24909703
TI  - Comfort blanket or clinical need? The role of follow-up for cancer survivors.

PMID- 24909704
TI  - Toxoplasma lymphadenitis diagnosed by fine-needle aspiration cytology: a rare
      finding.
AB  - BACKGROUND: There are only very few reports of cervical toxoplasma lymphadenitis
      being diagnosed exclusively via fine-needle aspiration cytology (with serology).
      CASE REPORT: We describe a case of toxoplasma lymphadenitis that was successfully
      diagnosed by fine-needle aspiration cytology. The case involved a male patient
      who was immunocompromised as a result of recurrent acute myelogenous leukaemia
      with cervical lymphadenopathy. The biopsy showed typical features of a well
      defined pseudocyst containing Toxoplasma gondii tachyzoites. CONCLUSION:
      Toxoplasma lymphadenitis is a common cause of lymph node enlargement. Fine-needle
      aspiration cytology is a useful method for diagnosing and differentiating
      toxoplasma lymphadenitis from more serious causes of lymphadenopathy, such as
      metastatic lymphadenopathy or lymphoma.

PMID- 24909705
TI  - The potential of recombinant human elastin-like polypeptides for drug delivery.
AB  - Mimicking the structure of natural proteins by recombinant biopolymers is a
      useful approach for the development of novel bioactive biomaterials with desired
      properties, that help elucidate molecular interactions in biological systems and
      elaborate strategies for tissue engineering and drug delivery purposes.
      Structurally based on elastin repeated motifs, recombinant human elastin-like
      polypeptides (HELPs) represent excellent examples of bio-inspired polymers
      proposed for tissue engineering, and recently exploited also for drug delivery
      applications. This Editorial reports on the latest advances in the research on
      HELP biopolymers for drug delivery and targeting applications. The main findings
      will be summarized with emphasis on the 'smart' properties of HELPs, which render
      this class of biopolymers particularly interesting in the whole biomedicine
      field. Considerations about further improvements of the current HELP-based
      systems will be provided, and a demonstration of the huge potential of HELPs in
      becoming leading material for drug delivery will be attempted. 

PMID- 24909706
TI  - EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food
      allergy.
AB  - Food allergy can result in considerable morbidity, impact negatively on quality
      of life, and prove costly in terms of medical care. These guidelines have been
      prepared by the European Academy of Allergy and Clinical Immunology's (EAACI)
      Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI
      position papers on adverse reaction to foods and three recent systematic reviews
      on the epidemiology, diagnosis, and management of food allergy, and provide
      evidence-based recommendations for the diagnosis and management of food allergy.
      While the primary audience is allergists, this document is relevant for all other
      healthcare professionals, including primary care physicians, and pediatric and
      adult specialists, dieticians, pharmacists and paramedics. Our current
      understanding of the manifestations of food allergy, the role of diagnostic
      tests, and the effective management of patients of all ages with food allergy is
      presented. The acute management of non-life-threatening reactions is covered in
      these guidelines, but for guidance on the emergency management of anaphylaxis,
      readers are referred to the related EAACI Anaphylaxis Guidelines. 

PMID- 24909707
TI  - New insights into the dynamics between reef corals and their associated
      dinoflagellate endosymbionts from population genetic studies.
AB  - The mutualistic symbioses between reef-building corals and micro-algae form the
      basis of coral reef ecosystems, yet recent environmental changes threaten their
      survival. Diversity in host-symbiont pairings on the sub-species level could be
      an unrecognized source of functional variation in response to stress. The
      Caribbean elkhorn coral, Acropora palmata, associates predominantly with one
      symbiont species (Symbiodinium 'fitti'), facilitating investigations of
      individual-level (genotype) interactions. Individual genotypes of both host and
      symbiont were resolved across the entire species' range. Most colonies of a
      particular animal genotype were dominated by one symbiont genotype (or strain)
      that may persist in the host for decades or more. While Symbiodinium are
      primarily clonal, the occurrence of recombinant genotypes indicates sexual
      recombination is the source of this genetic variation, and some evidence suggests
      this happens within the host. When these data are examined at spatial scales
      spanning the entire distribution of A. palmata, gene flow among animal
      populations was an order of magnitude greater than among populations of the
      symbiont. This suggests that independent micro-evolutionary processes created
      dissimilar population genetic structures between host and symbiont. The lower
      effective dispersal exhibited by the dinoflagellate raises questions regarding
      the extent to which populations of host and symbiont can co-evolve during times
      of rapid and substantial climate change. However, these findings also support a
      growing body of evidence, suggesting that genotype-by-genotype interactions may
      provide significant physiological variation, influencing the adaptive potential
      of symbiotic reef corals to severe selection.

PMID- 24909708
TI  - Time-resolved DNA stable isotope probing links Desulfobacterales- and
      Coriobacteriaceae-related bacteria to anaerobic degradation of benzene under
      methanogenic conditions.
AB  - To identify the microorganisms involved in benzene degradation, DNA-stable
      isotope probing (SIP) with 13C-benzene was applied to a methanogenic benzene
      degrading enrichment culture. Pyrosequencing of ribosomal RNA (rRNA) gene
      sequences revealed that the community structure was highly complex in spite of a
      3-year incubation only with benzene. The culture degraded 98% of approximately 1
      mM 13C-benzene and mineralized 72% of that within 63 d. The terminal restriction
      fragment length polymorphism (T-RFLP) profiles of the buoyant density fractions
      revealed the incorporation of 13C into two phylotypes after 64 d. These two
      phylotypes were determined to be Desulfobacterales- and Coriobacteriaceae-related
      bacteria by cloning and sequencing of the 16S rRNA gene in the 13C-labeled DNA
      abundant fraction. Comparative pyrosequencing analysis of the buoyant density
      fractions of 12C- and 13C-labeled samples indicated the incorporation of 13C into
      three bacterial and one archaeal OTUs related to Desulfobacterales,
      Coriobacteriales, Rhodocyclaceae, and Methanosarcinales. The first two OTUs
      included the bacteria detected by T-RFLP-cloning-sequencing analysis.
      Furthermore, time-resolved SIP analysis confirmed that the activity of all these
      microbes appeared at the earliest stage of degradation. In this methanogenic
      culture, Desulfobacterales- and Coriobacteriaceae-related bacteria were most
      likely to be the major benzene degraders.

PMID- 24909709
TI  - Termite nests as an abundant source of cultivable actinobacteria for
      biotechnological purposes.
AB  - A total of 118 actinobacterial isolates were collected from the three types of
      termite nests (mound, carton, and subterranean nests) to evaluate their potential
      as a source of bioactive actinobacteria with antimicrobial activity. The highest
      number (67 isolates) and generic abundance (7 known genera) of actinobacterial
      isolates were obtained from carton nests. Streptomyces was the dominant genus in
      each type of termite nest. In the non-Streptomyces group, Nocardia was the
      dominant genus detected in mound and carton nests, while Pseudonocardia was the
      dominant genus in subterranean nests. A discovery trend of novel species (<99%
      similarity in the 16S rRNA gene sequence) was also observed in the termite nests
      examined. Each type of termite nest housed >20% of bioactive actinobacteria that
      could inhibit the growth of at least one test organism, while 12 isolates,
      belonging to the genera Streptomyces, Amycolatopsis, Pseudonocardia,
      Micromonospora and Nocardia, exhibited distinct antimicrobial activities.
      Streptomyces sp. CMU-NKS-3 was the most distinct bioactive isolate. It was
      closely related to S. padanus MITKK-103T, which was confirmed by 99% similarities
      in their 16S rRNA gene sequences. The highest level of extracellular
      antimicrobial substances was produced by the isolate CMU-NKS-3, which was grown
      in potato dextrose broth and exhibited a wide range (6.10*10(-4)-1.25 mg mL(-1))
      of minimum inhibitory concentrations against diverse pathogens. We concluded that
      termite nests are an abundant source of bioactive strains of cultivable
      actinobacteria for future biotechnological needs.

PMID- 24909710
TI  - The tomato wilt fungus Fusarium oxysporum f. sp. lycopersici shares common
      ancestors with nonpathogenic F. oxysporum isolated from wild tomatoes in the
      Peruvian Andes.
AB  - Fusarium oxysporum is an ascomycetous fungus that is well-known as a soilborne
      plant pathogen. In addition, a large population of nonpathogenic F. oxysporum
      (NPF) inhabits various environmental niches, including the phytosphere. To obtain
      an insight into the origin of plant pathogenic F. oxysporum, we focused on the
      tomato (Solanum lycopersicum) and its pathogenic F. oxysporum f. sp. lycopersici
      (FOL). We collected F. oxysporum from wild and transition Solanum spp. and modern
      cultivars of tomato in Chile, Ecuador, Peru, Mexico, Afghanistan, Italy, and
      Japan, evaluated the fungal isolates for pathogenicity, VCG, mating type, and
      distribution of SIX genes related to the pathogenicity of FOL, and constructed
      phylogenies based on ribosomal DNA intergenic spacer sequences. All F. oxysporum
      isolates sampled were genetically more diverse than FOL. They were not pathogenic
      to the tomato and did not carry SIX genes. Certain NPF isolates including those
      from wild Solanum spp. in Peru were grouped in FOL clades, whereas most of the
      NPF isolates were not. Our results suggested that the population of NPF isolates
      in FOL clades gave rise to FOL by gaining pathogenicity. 

PMID- 24909711
TI  - Factors affecting biotic mercury concentrations and biomagnification through lake
      food webs in the Canadian high Arctic.
AB  - In temperate regions of Canada, mercury (Hg) concentrations in biota and the
      magnitude of Hg biomagnification through food webs vary between neighboring lakes
      and are related to water chemistry variables and physical lake features. However,
      few studies have examined factors affecting the variable Hg concentrations in
      landlocked Arctic char (Salvelinus alpinus) or the biomagnification of Hg through
      their food webs. We estimated the food web structure of six high Arctic lakes
      near Resolute Bay, Nunavut, Canada, using stable carbon (delta(13)C) and nitrogen
      (delta(15)N) isotopes and measured Hg (total Hg (THg) in char, the only fish
      species, and methylmercury (MeHg) in chironomids and zooplankton) concentrations
      in biota collected in 2010 and 2011. Across lakes, delta(13)C showed that benthic
      carbon (chironomids) was the dominant food source for char. Regression models of
      log Hg versus delta(15)N (of char and benthic invertebrates) showed positive and
      significant slopes, indicting Hg biomagnification in all lakes, and higher slopes
      in some lakes than others. However, no principal components (PC) generated using
      all water chemistry data and physical characteristics of the lakes predicted the
      different slopes. The PC dominated by aqueous ions was a negative predictor of
      MeHg concentrations in chironomids, suggesting that water chemistry affects Hg
      bioavailability and MeHg concentrations in these lower-trophic-level organisms.
      Furthermore, regression intercepts were predicted by the PCs dominated by
      catchment area, aqueous ions, and MeHg. Weaker relationships were also found
      between THg in small char or MeHg in pelagic invertebrates and the PCs dominated
      by catchment area, and aqueous nitrate and MeHg. Results from these high Arctic
      lakes suggest that Hg biomagnification differs between systems and that their
      physical and chemical characteristics affect Hg concentrations in lower-trophic
      level biota. 

PMID- 24909712
TI  - Pharmaceutically active compounds in sludge stabilization treatments: anaerobic
      and aerobic digestion, wastewater stabilization ponds and composting.
AB  - Sewage sludge disposal onto lands has been stabilized previously but still many
      pollutants are not efficiently removed. Special interest has been focused on
      pharmaceutical compounds due to their potential ecotoxicological effects.
      Nowadays, there is scarce information about their occurrence in different sludge
      stabilization treatments. In this work, the occurrence of twenty-two
      pharmaceutically active compounds has been studied in sludge from four sludge
      stabilization treatments: anaerobic digestion, aerobic digestion, composting and
      lagooning. The types of sludge evaluated were primary, secondary, anaerobically
      digested and dehydrated, composted, mixed, aerobically-digested and dehydrated
      and lagoon sludge. Nineteen of the twenty-two pharmaceutically active compounds
      monitored were detected in sewage sludge. The most contaminated samples were
      primary sludge, secondary sludge and mixed sludge (the average concentrations of
      studied compounds in these sludges were 179, 310 and 142 MUg/kg dm, respectively)
      while the mean concentrations found in the other types of sewage sludge were 70
      MUg/kg dm (aerobically-digested sludge), 63 MUg/kg dm (lagoon sludge), 12 MUg/kg
      dm (composted sludge) and 8 MUg/kg dm (anaerobically-digested sludge). The
      antibiotics ciprofloxacin and norfloxacin were found at the highest concentration
      levels in most of the analyzed sludge samples (up to 2660 and 4328 MUg/kg dm,
      respectively). Anaerobic-digestion treatment reduced more considerably the
      concentration of most of the studied compounds than aerobic-digestion (especially
      in the case of bezafibrate and fluoroquinolones) and more than anaerobic
      stabilization ponds (in the case of acetaminophen, atenolol, bezafibrate,
      carbamazepine, 17alpha-ethinylestradiol, naproxen and salicylic acid).
      Ecotoxicological risk assessment, of sludge application onto soils, has also been
      evaluated. Risk quotients, expressed as the ratio between the predicted
      environmental concentration and the predicted non-effect concentration, were
      lower than 1 for all the pharmaceutically active compounds so no significant
      risks are expected to occur due to the application of sewage sludge onto soils,
      except for 17alpha-ethinylestradiol when chronic toxicity was considered.

PMID- 24909713
TI  - Hospital nurses' work motivation.
AB  - BACKGROUND: The knowledge surrounding nurses' work motivation is currently
      insufficient, and previous studies have rarely taken into account the role of
      many influential background factors. AIM: This study investigates the motivation
      of Estonian nurses in hospitals, and how individual and organisational background
      factors influence their motivation to work. METHODS: The study is quantitative
      and cross-sectional. An electronically self-reported questionnaire was used for
      data collection. The sample comprised of 201 Registered Nurses working in various
      hospital settings in Estonia. Data were analysed using descriptive statistics,
      two-sample Wilcoxon rank-sum (Mann-Whitney) test, Kruskal-Wallis equality-of
      populations rank test and Spearman's correlation. RESULTS: Both extrinsic and
      intrinsic motivations were noted among hospital nurses. Nurses were moderately
      externally motivated (M = 3.63, SD = 0.89) and intrinsically strongly motivated
      (M = 4.98, SD = 1.03). A nurses' age and the duration of service were positively
      correlated with one particular area of extrinsic work motivation, namely
      introjected regulation (p < 0.001). Nurses who had professional training over 7
      days per year had both a higher extrinsic motivation (p = 0.016) and intrinsic
      work motivation (p = 0.004). CONCLUSIONS: The findings expand current knowledge
      of nurses' work motivation by describing the amount and orientation of work
      motivation among hospital nurses and highlighting background factors which should
      be taken into account in order to sustain and increase their intrinsic work
      motivation. The instrument used in the study can be an effective tool for nurse
      managers to determine a nurse's reasons to work and to choose a proper
      motivational strategy. Further research and testing of the instrument in
      different countries and in different contexts of nursing is however required.

PMID- 24909714
TI  - New nucleos(t)ide analogue monoprophylaxis after cessation of hepatitis B
      immunoglobulin is effective against hepatitis B recurrence.
AB  - New nucleos(t)ide agents (NAs) [entecavir (ETV) and tenofovir (TDF)] have made
      hepatitis B immunoglobulin (HBIG)-sparing protocols an attractive approach
      against hepatitis B virus (HBV) recurrence after liver transplantation (LT).
      Twenty-eight patients transplanted for HBV cirrhosis in our centre were
      prospectively evaluated. After LT, each patient received HBIG (1000 IU IM/day for
      7 days and then monthly for 6 months) plus ETV or TDF and then continued with ETV
      or TDF monoprophylaxis. All patients had undetectable HBV DNA at the time of LT,
      and they were followed up with laboratory tests including glomerular filtration
      rate (GFR) after LT. All patients (11 under ETV and 17 under TDF) remained
      HBsAg/HBV DNA negative during the follow-up period [median: 21 (range 9-43)
      months]. GFR was not different between TDF and ETV groups of patients at 6 and 12
      months and last follow-up (P value >0.05 for all comparisons). The two groups of
      patients were similar regarding their ratio of maximum rate of tubular phosphate
      reabsorption to the GFR (TmP/GFR). In conclusion, in this prospective study, we
      showed for the first time that maintenance therapy with ETV or TDF
      monoprophylaxis after 6 months of low-dose HBIG plus ETV or TDF after LT is
      highly effective and safe. 

PMID- 24909715
TI  - Lavender essential oil inhalation suppresses allergic airway inflammation and
      mucous cell hyperplasia in a murine model of asthma.
AB  - AIMS: Lavender essential oil (Lvn) has been reported to have anti-inflammatory
      effects. Bronchial asthma is characterized by bronchial allergic inflammation
      with airway remodeling. Therefore, we evaluated the anti-inflammatory effect of
      Lvn on experimentally induced bronchial asthma in a murine model. MAIN METHODS:
      BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA) at
      days 0 and 14, and subsequently challenged with nebulized OVA on days 28-30
      (Control-Asthma group). Mice in the treatment group inhaled Lvn on days 14-31
      (Lvn-Asthma group). The allergic inflammatory response was determined on days 32
      and 33. KEY FINDINGS: An increase in airway resistance was inhibited in the Lvn
      Asthma group than in the Control-Asthma group. The Lvn-Asthma group showed lower
      total cell numbers and eosinophils in bronchoalveolar lavage (BAL) fluids and
      peribronchial and perivascular tissues when compared with the Control-Asthma
      group. The Lvn-Asthma group also had less mucin hyperplasia than the Control
      Asthma group. Furthermore, the Lvn-Asthma group showed lower interleukin (IL)-5
      and IL-13 cytokine levels in BAL fluids, as well as reduced IL-4 and IL-5 mRNA
      expression in lung tissue, compared with the Control-Asthma group and determined
      by FlowCytomix and reverse transcriptase-polymerase chain reaction (RT-PCR),
      respectively. In addition, Lvn inhalation reduced Muc5b mRNA expression in the
      lungs without significantly changing the expression of Muc5ac mRNA. SIGNIFICANCE:
      Lvn inhibits allergic inflammation and mucous cell hyperplasia with suppression
      of T-helper-2 cell cytokines and Muc5b expression in a murine model of asthma.
      Consequently, Lvn may be useful as an alternative medicine for bronchial asthma.

PMID- 24909716
TI  - Evaluation of compliance to national nutrition policies in summer day camps.
AB  - OBJECTIVE: The National Afterschool Association (NAA) standards specify the role
      of summer day camps (SDC) in promoting healthy nutrition habits of the children
      attending, identifying foods and beverages to be provided to children and staff
      roles in promoting good nutrition habits. However, many SDC do not provide meals.
      Currently, national guidelines specifying what children are allowed to bring to
      such settings do not exist, nor is there a solid understanding of the current
      landscape surrounding healthy eating within SDC. DESIGN: A cross-sectional study
      design using validated measures with multiple observations was used to determine
      the types of foods and beverages brought to SDC programmes. SETTING: Four large
      scale, community-based SDC participated in the study during summer 2011.
      SUBJECTS: The types of foods and beverages brought by children (n 766) and staff
      (n 87), as well as any instances of staff promoting healthy eating behaviours,
      were examined via direct observation over 27 d. Additionally, the extent to which
      current foods and beverages at SDC complied with NAA standards was evaluated.
      RESULTS: Less than half of the children brought water, 47% brought non-100%
      juices, 4% brought soda, 4% brought a vegetable and 20% brought fruit. Staff
      foods and beverages modelled similar patterns. Promotion of healthy eating by
      staff was observed <1% of the time. CONCLUSIONS: Findings suggest that foods and
      beverages brought to SDC by children and staff do not support nutrition standards
      and staff do not regularly promote healthy eating habits. To assist, professional
      development, parent education and organizational policies are needed.

PMID- 24909717
TI  - Amino acid derivatives of adamantane carbocycle are capable of inhibiting
      replication of highly virulent avian influenza A/H5N1 virus.
AB  - We studied the capacity amino acid derivatives of adamantane to inhibit
      replication of highly virulent avian influenza A/duck/Novosibirsk/56/05 (H5N1)
      virus in cultures of swine embryonic kidney cells. Amino acid derivatives of
      adamantane H-His-Rem and Ad(CH2-Ser-OMe)2 were characterized by lower toxicity
      than remantadine previously used in the treatment of influenza. Histidine
      containing adamantane derivative (H-His-Rem) was the most effective and low-toxic
      inhibitor of influenza A/H5N1 virus replication and can be recommended for
      clinical trials to produce a preparation for the treatment and prevention of
      influenza. 

PMID- 24909718
TI  - Analysis of the association of polymorphic loci rs917997 in IL18RAP gene and
      rs187238 in IL18 gene with the risk for non-Hodgkin's malignant lymphomas in
      Novosibirsk population.
AB  - We analyzed the association of polymorphic variants of rs917997 (G/A) locus in
      IL18RAP gene and rs187238 (G/C) locus in IL18 gene with the risk of malignant non
      Hodgkin's lymphomas in Novosibirsk population. Allele and genotype frequencies of
      the above loci were determined in patients (243 persons) and control group (371
      persons) and compared using chi(2) test. None of the analyzed loci showed
      statistically significant association with the risk of malignant non-Hodgkin's
      lymphomas.

PMID- 24909719
TI  - Complex of molecular genetic and immunohistochemical methods for detection of
      human papillomavirus in the bladder cancer epithelium.
AB  - A battery of tests for detection human papillomavirus DNA, mRNA corresponding to
      viral oncogenes, and viral oncoprotein E7 in cancer bladder urothelium was
      piloted in 35 samples of bladder cancer. DNA of human papillomavirus type 16
      (causes cervical cancer) was found in 16 (46%) samples; E6/E7 oncogene transcript
      and E7 oncoprotein of human papillomavirus type 16 were detected in 10 and 7
      human papillomavirus DNA-positive samples, respectively. These findings attest to
      association of bladder cancer with human papillomavirus in Russia.

PMID- 24909720
TI  - Photodynamic therapy of experimental sarcoma M-1 with boronated chlorine as a
      photosensitizer.
AB  - Using rat model of experimental sarcoma M-1 we studied the efficacy of
      photodynamic therapy with boronated chlorine as a photosensitizer in doses of
      1.25, 2.5, 5.0, and 10.0 mg/ kg body weight. Laser irradiation was performed at
      energy densities of 150, 300 J/cm(2) and power density of 0.25 and 0.42 W/cm(2).
      Treatment efficacy was evaluated by the percentage of animals with complete tumor
      regression, percentage of tumor recurrence and, in cases of its growth, by tumor
      growth coefficient. The efficacy of photodynamic therapy depended on the dose of
      boronated chlorine and parameters of the laser irradiation. Optimal conditions
      were the dose of 2.5 mg/kg at laser energy density of 300 J/cm(2) and power
      density of 0.42 W/cm(2) and a dose of 5.0 mg/kg at 150 J/cm(2) and 0.25 W/cm(2). 

PMID- 24909721
TI  - Short peptides stimulate serotonin expression in cells of brain cortex.
AB  - Peptides Glu-Asp-Arg and Lys-Glu-Asp stimulate serotonin expression in aging
      cultures of brain cortex cells. Peptide regulation of 5-tryptophan hydroxylase
      gene encoding the enzyme involved in serotonin synthesis was demonstrated by the
      molecular docking method. The CCTGCC nucleotide sequence in 5-tryptophan
      hydroxylase gene was found to be complementary to these peptides. Hence, Glu-Asp
      Arg and Lys-Glu-Asp peptides epigenetically regulate serotonin synthesis in the
      brain cortex, which indicates their neuro- and geroprotective activities.

PMID- 24909722
TI  - Physiological parameters of Macaca fascicularis immunized with anti-rubella
      vaccine with germanium-based adjuvants.
AB  - Clinical status, hematological and biochemical parameters, and allergenic
      activity of organogermanium compounds used as adjuvants in complex with
      preparation from Orlov rubella virus vaccine strain and reference commercial anti
      rubella vaccine based on Wistar RA 27/3 strain were studied on Macaca
      fascilcularis of both genders. Physiological parameters of monkeys immunized with
      the Russian and foreign rubella virus vaccine strains with and without adjuvants
      did not differ. The adjuvants were inessential for the safety of vaccines
      (absence of toxicity, reactogenic activity, or allergenic activity) in
      preclinical studies on lower primates.

PMID- 24909723
TI  - Efficiency of transplantation of human placental/umbilical blood cells to rats
      with severe spinal cord injury.
AB  - The effects of a single intravenous injection of human umbilical blood were
      studied on the model of severe spinal cord contusion injury in rats. Rats
      receiving no umbilical blood (spontaneous recovery) served as the control. All
      rats exhibited pronounced hind limb paraplegia and autonomic dysfunction of
      pelvic organs after the injury. Recovery of the hind limb function was evaluated
      by loading tests and locomotor activity testing in the open field using BBB score
      for open-field testing. Testing was carried out weekly for 8 weeks after the
      injury. Open-field testing showed a significant (p < 0.05) increase of the rate
      and volume of the hind limb motor activity recovery in the groups receiving
      umbilical blood infusions. 

PMID- 24909724
TI  - Effects of nanosized lithium carbonate particles on intact muscle tissue and
      tumor growth.
AB  - The effects of nanosized lithium carbonate particles on muscle tissue structure
      and development of experimental hepatocarcinoma-29 transplanted into the hip were
      studied in CBA mice. Necrotic changes in all structural components of the muscle
      were detected after intramuscular injection of nanosized lithium carbonate
      particles to intact animals. Regeneration of the muscle fibers after lithium
      carbonate treatment was associated with a significant increase in macrophage
      count, number of microvessels, activation of fibroblasts, and complete recovery
      of the organ structure. Injection of lithium carbonate nanoparticles at the
      periphery of tumor growth caused tumor cell necrosis, destruction of the vascular
      bed, and attraction of neutrophils and macrophages to the tumor focus. After the
      preparation was discontinued, the tumor developed with lesser number of vessels,
      smaller tumor cells, and lesser deformation of the cell nuclei structure.

PMID- 24909725
TI  - Effects of overweight and obesity on the spermogram values and levels of
      reproductive hormones in the male population of the European north of Russia.
AB  - The effects of excessive body weight and obesity on the reproductive potential of
      the male population of the Russian European North (Arkhangelsk), characterized by
      a specific northern adaptive metabolic type were studied. Spermogram values and
      levels of reproductive hormones were compared in men with normal and excessive
      body weights and with obesity, using body weight index and waist circumference as
      indicators of abdominal visceral obesity. Irrespective of the indicator used, the
      total count of spermatozoa and their concentration in the ejaculate were
      significantly lower in men with obesity than in overweight men. Serum
      testosterone concentration was lower in obese men in comparison with men with
      normal body weights. Higher spermatogenesis, but not testosterone values, were
      observed in men with excessive body weight vs. men with normal body weights or
      obesity, which was presumably a characteristic feature of the northern metabolic
      type.

PMID- 24909726
TI  - Evaluation of ATP content in hair bulbs in human scalp.
AB  - The content of ATP in scalp hair bulbs in humans was measured in the hair roots
      from 15 healthy volunteers. Light and electron microscopy confirmed the presence
      of outer and an inner root sheaths in the root of pulled out anagen hair.
      Incubation of samples in buffer solution led to extraction of ATP, which was
      measured by the chemiluminescent method. Mechanic disintegration of hair bulbs
      and their freezing-defrosting did not increase ATP output. The results of
      microscopy indicated that ATP extraction procedure was associated with separation
      of the outer radical sheath from the inner one without impairing the structure of
      the inner sheath. The mean content of ATP was 12 +/- 2 pmol per bulb. The use of
      pulled out hair bulbs for ATP measurements simplified the procedure as involved
      no surgical removal of follicles.

PMID- 24909727
TI  - Isolation of mesenchymal stromal cells from extraembryonic tissues and their
      characteristics.
AB  - We describe a method of isolation of human mesenchymal stromal cells from the
      umbilical cord (Wharton's jelly) and human placenta: amnion, placental villi, and
      trophoblast. Morphology, immunophenotypic characteristics, and differentiation
      potencies of isolated cells were studied. The capacity of mesenchymal stromal
      cells from extraembryonic tissues to osteogenic, adipogenic, and chondrogenic
      differentiation was demonstrated and the dynamics of this process was described.
      The isolated cells met the criteria for multipotent mesenchymal stem cells. 

PMID- 24909728
TI  - Allogenic cardiomyoblasts raised from human mesenchymal stem cells in the therapy
      of radiation cardiomyopathy and pericarditis: case report.
AB  - The use of triple systemic transplantation of cardiomyoblasts raised from the
      culture of allogenic bone marrow mesenchymal stem cells of a healthy donor
      according to the new medical technology licensed by Federal Service on
      Surveillance in Healthcare in the therapy of a patient with late radiation
      cardiomyopathy and radiation exudative pericarditis developed 45 years after
      radiation therapy for Hodgkin lymphoma. High efficiency of systemic
      transplantation of mesenchymal stem cells partially differentiated towards
      cardiomyocytes was demonstrated. The therapeutic effect persists for more than 2
      years. Possible mechanisms of the therapeutic effect of this type of stem cells
      and the prospects of using cell therapy in the treatment of late radiation
      injuries of vital organs and tissues are discussed. 

PMID- 24909730
TI  - QSAR models for thiophene and imidazopyridine derivatives inhibitors of the Polo
      Like Kinase 1.
AB  - The inhibitory activity of 103 thiophene and 33 imidazopyridine derivatives
      against Polo-Like Kinase 1 (PLK1) expressed as pIC50 (-logIC50) was predicted by
      QSAR modeling. Multivariate linear regression (MLR) was employed to model the
      relationship between 0D and 3D molecular descriptors and biological activities of
      molecules using the replacement method (MR) as variable selection tool. The 136
      compounds were separated into several training and test sets. Two splitting
      approaches, distribution of biological data and structural diversity, and the
      statistical experimental design procedure D-optimal distance were applied to the
      dataset. The significance of the training set models was confirmed by
      statistically higher values of the internal leave one out cross-validated
      coefficient of determination (Q2) and external predictive coefficient of
      determination for the test set (Rtest2). The model developed from a training set,
      obtained with the D-optimal distance protocol and using 3D descriptor space along
      with activity values, separated chemical features that allowed to distinguish
      high and low pIC50 values reasonably well. Then, we verified that such model was
      sufficient to reliably and accurately predict the activity of external diverse
      structures. The model robustness was properly characterized by means of standard
      procedures and their applicability domain (AD) was analyzed by leverage method.

PMID- 24909729
TI  - Upregulation of COX-2 in the lung cancer promotes overexpression of multidrug
      resistance protein 4 (MRP4) via PGE2-dependent pathway.
AB  - It is apparent that lung cancer is associated with inflammation, with
      accompanying hallmark elevations of cyclooxygenase 2 (COX-2) and prostaglandin E2
      (PGE2) levels. However, the effects of these changes on MRP efflux transporters
      have not been thoroughly investigated before. Here, we report that upregulation
      of COX-2 can induce overexpression of MRP4 in both A549 non-small-cell lung
      cancer cell lines and mouse lung cancer models. In A549 cells, phorbol 12
      myristate 13-acetate (PMA) treatment induced upregulation of COX-2 and MRP4
      together, but not other MRP transporters. Transient overexpression of human COX-2
      cDNA also specifically increased COX-2 and MRP4. Moreover, COX inhibitor
      treatment and COX-2-specific siRNA significantly inhibited the upregulation of
      MRP4. Additionally, PMA-treatment increased extracellular PGE2 levels, likely due
      to increased MRP4 function. Likewise, COX-2-specific siRNA reduced extracellular
      PGE2 levels. Furthermore, COX-2 upregulation resulted in an increase in mPGES-1,
      an enzyme responsible for PGE2 production. Finally, metastasized lung cancer
      model mice exhibited increased expression levels of COX-2 and MRP4, as well as
      mPGES-1. In conclusion, the present study suggests that overexpression of MRP4 in
      lung cancer may be attributable to COX-2 upregulation via a PGE2-dependent
      pathway. 

PMID- 24909731
TI  - Development of novel carrier(s) mediated tuberculosis vaccine: more than a tour
      de force.
AB  - Despite worldwide availability of the vaccines against most of the infectious
      diseases, BCG and various programs such as Directly Observed Treatment Short
      course (DOTS) to prevent tuberculosis still remains one of the most deadly forms
      of the disease affecting millions of people globally. The evolution of multi drug
      resistant strains (MDR) has increased the complexity further. Although currently
      available marketed BCG vaccine has shown sufficient protection against childhood
      tuberculosis, it has failed to prevent the most common form of disease i.e.,
      pulmonary tuberculosis in adults. However, various vaccine candidates have
      already entered phase I clinical trials and have shown promising outcomes. The
      most prominent amongst them is the heterologous prime-boost approach, which shows
      a great promise towards designing and development of a new efficacious
      tuberculosis vaccine. It has also been shown that the use of various viral and
      non-viral vectors as carriers for the potential vaccine candidates will further
      boost their effect on subsequent immunization. In this review, we briefly
      summarize the potential of a few novel nano-carriers for developing effective
      vaccination strategies against tuberculosis. 

PMID- 24909732
TI  - Evaluation of T and B lymphocyte function in clinical practice using a flow
      cytometry based proliferation assay.
AB  - The golden standard for functional evaluation of immunodeficiencies is the
      incorporation of [(3)H]-thymidine in a proliferation assay stimulated with
      mitogens. Recently developed whole blood proliferation assays have the advantage
      of parallel lymphocyte lineage analysis and in addition provide a non-radioactive
      alternative. Here we evaluate the Flow-cytometric Assay for Specific Cell
      mediated Immune-response in Activated whole blood (FASCIA) in a comparison with
      [(3)H]-thymidine incorporation in four patients with severe combined
      immunodeficiency. The threshold for the minimum number of lymphocytes required
      for reliable responses in FASCIA is determined together with reference values
      from 100 healthy donors when stimulated with mitogens as well as antigen specific
      stimuli. Finally, responses against PWM and SEA+SEB stimuli are conducted with
      clinically relevant immunomodulatory compounds. We conclude that FASCIA is a
      rapid, stable and sensitive functional whole blood assay that requires small
      amounts of whole blood that can be used for reliable assessment of lymphocyte
      reactivity in patients. 

PMID- 24909734
TI  - Serum soluble urokinase plasminogen activator receptor in alcoholics: relation to
      liver disease severity, fibrogenesis, and alcohol use.
AB  - BACKGROUND AND AIM: Heavy alcohol consumption may lead to development of liver
      disease and the need for non-invasive parameters for detecting those at risk is
      widely acknowledged. METHODS: We measured serum soluble urokinase-type
      plasminogen activator receptor (suPAR) levels from 63 patients with alcoholic
      liver disease (ALD), 57 heavy drinkers without apparent liver disease, and 39
      controls who were either moderate drinkers or abstainers. RESULTS: The highest
      serum suPAR concentrations were detected in patients with ALD (P < 0.001) showing
      high diagnostic accuracy in differentiating ALD patients from heavy drinkers
      without liver disease (area under curve 0.921, P < 0.001). Levels of suPAR
      correlated positively with serum markers of fibrogenesis (aminoterminal
      propeptide of type III procollagen and hyaluronic acid) (P < 0.001), with
      clinical (combined clinical and laboratory index P < 0.01) and morphological
      (combined morphological index P < 0.05) indices of liver disease severity and
      with the stage of fibrosis (P < 0.01). The suPAR concentrations were also
      elevated in heavy drinkers when compared with healthy controls (P < 0.001).
      CONCLUSION: The data indicate that serum suPAR concentrations are increased as a
      result of heavy alcohol consumption and further with development of ALD, showing
      a good diagnostic performance in detecting those with liver disease. The
      association with the histological severity of ALD and correlation with fibrosis
      indicates potential of serum suPAR also as a prognostic marker in ALD.

PMID- 24909735
TI  - Topotecan hydrochloride liposomes incorporated into thermosensitive hydrogel for
      sustained and efficient in situ therapy of H22 tumor in Kunming mice.
AB  - Abstract Topotecan hydrochloride (TPT) has potential for the treatment of ovarian
      cancer, but the activity of TPT tends to decrease due to the ring-opening at
      physiological pH. In this study, we proposed to incorporate TPT liposomes into
      injectable thermosensitive in situ hydrogel, consisting of chitosan (CS) and beta
      glycerophosphate (beta-GP), for sustained release and preservation of active
      lactone form of TPT. The rheology studies were carried out to investigate the sol
      gel temperature, flow behavior and viscosity of these CS/beta-GP systems. The
      optimized formulation exhibited sol-gel transition at 40.2 +/- 0.4  degrees C,
      with pseudoplastic flow behavior. The drug release rate of TPT liposomes loaded
      CS/beta-GP hydrogel in phosphate buffer saline (pH = 7.4) was found to be slowed
      down, and the lactone fraction of TPT in the hydrogel matrix was maintaining 40%
      after 50 h. In addition, the antitumor efficacy in Kunming mice bearing Hepatoma
      22 tumor, after intratumoral injection of TPT liposomes loaded CS/beta-GP
      hydrogel, was higher than that of TPT in saline and TPT in CS/beta-GP hydrogel.
      Those results demonstrated that TPT liposomes loaded CS/beta-GP hydrogel could
      become a potential formulation for improving the antitumor efficacy of TPT and
      suggested an important technology platform for intratumoral administration of
      derivative of camptothecin-family drugs.

PMID- 24909733
TI  - TAOK3, a novel genome-wide association study locus associated with morphine
      requirement and postoperative pain in a retrospective pediatric day surgery
      population.
AB  - Candidate gene studies have revealed limited genetic bases for opioid analgesic
      response variability. Genome-wide association studies facilitate impartial
      queries of common genetic variants, allowing identification of novel genetic
      contributions to drug effect. Illumina (Illumina Inc, San Diego, CA, USA) single
      nucleotide polymorphism (SNP) arrays were used to investigate SNP associations
      with total morphine requirement as a quantitative trait locus and with
      postoperative pain in a retrospective population of opioid-naive children ages 4
      18years who had undergone day surgery tonsillectomy and adenoidectomy. In an
      independent replication cohort, significant genome-wide association studies
      identified SNPs were assayed using TaqMan probes. Among 617 comprehensively
      phenotyped children, the 277 subjects of European Caucasian (EC) ancestry
      demonstrated nominal association between morphine dose and a series of novel SNPs
      (top rs795484, P=1.01 * 10(-6) and rs1277441, P=2.77 * 10(-6)) at the TAOK3
      locus. Age, body mass index, and physical status were included covariates.
      Morphine requirement averaged 132.4 MUg/kg (SD 40.9). Each minor allele at
      rs795484 (guanine [G]>adenine [A]) contributed +17.6 MUg/kg (95% confidence
      interval [CI] 10.7-24.4) to dose. Effect direction and magnitude were replicated
      in an independent cohort of 75 EC children (P<0.05). No association with morphine
      dose was detected in African Americans (AA) (n=241). Postoperative pain scores >=
      7/10 were associated with rs795484 (G>A) in the EC cohort (odds ratio 2.35, 95%
      CI 1.56-3.52, P<0.00005) and this association replicated in AA children (odds
      ratio 1.76, 95% CI 1.14-2.71, P<0.01). Variants in TAOK3 encoding the
      serine/threonine-protein kinase, TAO3, are associated with increased morphine
      requirement in children of EC ancestry and with increased acute postoperative
      pain in both EC and AA subjects.

PMID- 24909736
TI  - Transdermal delivery of meloxicam using niosomal hydrogels: in vitro and
      pharmacodynamic evaluation.
AB  - Abstract Non-ionic surfactant vesicles were prepared using Span-60 and
      cholesterol in the mass ratios of 1:1, 2:1, 1:2 and 3:1 for transdermal delivery
      of an anti-inflammatory drug meloxicam (MXM). The drug encapsulation efficiencies
      and particle size were observed in the range of 32.9-80.7% and 56.5-133.4 nm,
      respectively. Three different gel bases were also prepared using Poloxamer-407,
      Chitosan and Carbopol-934 as polymers to study the performance of the in vitro
      release of the drug. Prepared gels were also converted into niosomal gels. In
      vitro release characteristics of MXM from different gels were carried out using
      dialysis membrane in phosphate buffer (pH 7.4). The poloxamer-407 gel or niosomal
      poloxamer-407 gel showed the superior drug release over the other formulations.
      The release data were treated with various mathematical models to assess the
      relevant parameters. The results showed that the release of MXM from the prepared
      gels and niosomal gels followed Higuchi's diffusion model. The flux of MXM was
      found to be independent on the viscosity of the formulations. The anti
      inflammatory effects of MXM from different niosomal gel formulations were
      evaluated using carrageenan-induced rat paw edema method, which showed
      superiority of niosomal gels over conventional gels.

PMID- 24909737
TI  - Intercellular communication by extracellular vesicles and their microRNAs in
      asthma.
AB  - PURPOSE: Extracellular vesicles (EVs) such as exosomes and microvesicles are
      phospholipid bilayer-enclosed vesicles that are recognized as novel tools for
      intercellular communications and as biomarkers for several diseases. They contain
      various DNAs, proteins, mRNAs, and microRNAs (miRNAs) that have potential
      diagnostic and therapeutic purposes. Their biological roles have attracted
      significant interest in the pulmonary field because their vesicle composition and
      miRNA content have the ability to transfer biological information to recipient
      cells and play an important role in pulmonary inflammatory and allergic diseases.
      Asthma is a chronic inflammatory disease of the airways, and it is characterized
      by variable and recurring symptoms and reversible airflow obstruction. The
      purpose of this review was to discuss the function of EVs and their miRNAs in
      asthma, with a focus on the biological properties and biogenesis of EVs, their
      pathophysiologic roles, and their potential use as biomarkers and therapies for
      asthma. METHODS: We review the findings from several articles on EVs and their
      miRNAs in asthma and provide illustrative references. FINDINGS: A few studies
      have reported on the biological function of bronchoalveolar lavage fluid-derived
      EVs in asthmatic progression. In the lungs, EVs might regulate airway
      inflammation and allergic reactions through their paracrine effects. Furthermore,
      circulating miRNAs have been found to be associated with EVs. IMPLICATION: EV
      mediated miRNAs can be used as biomarkers in asthma.

PMID- 24909738
TI  - Realization of deep subwavelength resolution with singular media.
AB  - The record of imaging resolution has kept being refreshed in the past decades and
      the best resolution of hyperlenses and superlenses so far is about one out of
      tens in terms of wavelength. In this paper, by adopting a hybrid concept of
      transformation optics and singular media, we report a broadband meta-lens design
      methodology with ultra-high resolution. The meta-lens is made of subwavelength
      metal/air layers, which exhibit singular medium property over a broad band. As a
      proof of concept, the subwavelength imaging ability is demonstrated over a broad
      frequency band from 1.5-10 GHz with the resolution varying from 1/117 to 1/17
      wavelength experimentally.

PMID- 24909739
TI  - Integrating bottom-up internalist views of emotional feelings with top-down
      externalist views: might brain affective changes constitute reward and punishment
      effects within animal brains?

PMID- 24909741
TI  - Increased interleukin 33 in patients with neuro-Behcet's disease: correlation
      with MCP-1 and IP-10 chemokines.

PMID- 24909740
TI  - Neutrophil transcriptional profile changes during transit from bone marrow to
      sites of inflammation.
AB  - It has recently been established that neutrophils, the most abundant leukocytes,
      are capable of changes in gene expression during inflammatory responses. However,
      changes in the transcriptome as the neutrophil leaves the bone marrow have yet to
      be described. We hypothesized that neutrophils are transcriptionally active cells
      that alter their gene expression profiles as they migrate into the vasculature
      and then into inflamed tissues. Our goal was to provide an overview of how the
      neutrophil's transcriptome changes as they migrate through different compartments
      using microarray and bio-informatic approaches. Our study demonstrates that
      neutrophils are highly plastic cells where normal environmental cues result in a
      site-specific neutrophil transcriptome. We demonstrate that neutrophil genes
      undergo one of four distinct expression change patterns as they move from bone
      marrow through the circulation to sites of inflammation: (i) continuously
      increasing; (ii) continuously decreasing; (iii) a down-up-down; and (iv) an up
      down-up pattern. Additionally, we demonstrate that the neutrophil migration
      signaling network and the balance between anti-apoptotic and pro-apoptotic
      signaling are two of the main regulatory mechanisms that change as the neutrophil
      transits through compartments. 

PMID- 24909743
TI  - Feasibility of trialling cord blood stem cell treatments for cerebral palsy in
      Australia.
AB  - AIM: Umbilical cord blood may have therapeutic benefit in children with cerebral
      palsy (CP), but further studies are required. On first appearance it seems that
      Australia is well placed for such a trial because we have excellence in CP
      research backed by extensive CP registers, and both public and private cord blood
      banks. We aimed to examine the possibilities of conducting a trial of autologous
      umbilical cord blood cells (UCBCs) as a treatment for children with CP in
      Australia. METHODS: Data linkages between CP registers and cord blood banks were
      used to estimate potential participant numbers for a trial of autologous UCBCs
      for children with CP. RESULTS: As of early 2013, one Victorian child with CP had
      cord blood stored in the public bank, and between 1 and 3 children had their cord
      blood stored at Cell Care Australia (private cord blood bank). In New South
      Wales, we counted two children on the CP register who had their stored cord blood
      available in early 2013. We estimate that there are between 10 and 24 children
      with CP of any type who have autologous cord blood available across Australia.
      CONCLUSIONS: In nations with small populations like Australia, combined with
      Australia's relatively low per capita cord blood storage to date, it is not
      currently feasible to conduct trials of autologous UCBCs for children with CP.
      Other options must be explored, such as allogeneic UCBCs or prospective trials
      for neonates at risk of CP.

PMID- 24909742
TI  - Hypoxia-inducible hydrogels.
AB  - Oxygen is vital for the existence of all multicellular organisms, acting as a
      signalling molecule regulating cellular activities. Specifically, hypoxia, which
      occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role
      during development, regeneration and cancer. Here we report a novel hypoxia
      inducible (HI) hydrogel composed of gelatin and ferulic acid that can form
      hydrogel networks via oxygen consumption in a laccase-mediated reaction. Oxygen
      levels and gradients within the hydrogels can be accurately controlled and
      precisely predicted. We demonstrate that HI hydrogels guide vascular
      morphogenesis in vitro via hypoxia-inducible factors activation of matrix
      metalloproteinases and promote rapid neovascularization from the host tissue
      during subcutaneous wound healing. The HI hydrogel is a new class of biomaterials
      that may prove useful in many applications, ranging from fundamental studies of
      developmental, regenerative and disease processes through the engineering of
      healthy and diseased tissue models towards the treatment of hypoxia-regulated
      disorders. 

PMID- 24909744
TI  - Applying an observational lens to identify parental behaviours associated with
      children's homework motivation.
AB  - BACKGROUND: Extant research has traditionally associated children's achievement
      motivation with socio-emotional parental behaviours such as demonstrations of
      affect, responsiveness, and the degree of parental control. AIMS: This study
      explored the extent to which parental socio-emotional and instructional
      behaviours (including the contingency of instructional scaffolding) both related
      to children's mastery and performance tendencies towards homework-like
      activities. SAMPLE: The study involved nine underachieving primary-aged children
      and their parents, with four children showing predominantly mastery-oriented
      behaviours in the homework context and five showing predominantly performance
      oriented behaviours. METHODS: An in-depth observational analysis of video
      recorded parent-child interactions during four homework-like sessions was carried
      out for each case. Socio-emotional and instructional parental behaviours were
      coded and subjected to nonparametric quantitative analyses. Subsequently, thick
      descriptions of parent-child interactions were used to identify critical aspects
      of parental assistance. RESULTS: Moderate cognitive demand was associated with
      mastery orientation, while negative affect was related to performance
      orientation. As revealed quantitatively and qualitatively, socio-emotional and
      instructional parental behaviours were also associated with each other, forming
      distinct profiles of parental behaviours related to children's homework
      motivation. CONCLUSIONS: The findings support the idea that instructional
      parental behaviours are as important as socio-emotional ones in the analysis of
      children's homework motivation. The value of observational methods in
      investigating the target variables is discussed.

PMID- 24909746
TI  - 1064-nm Q-switched Nd:YAG laser is an effective and safe approach to treat
      xanthelasma palpebrarum in Asian population.

PMID- 24909747
TI  - Improvement in the cutaneous disease activity of patients with dermatomyositis is
      associated with a better quality of life.
AB  - BACKGROUND: Cutaneous dermatomyositis (DM) disease activity is associated with
      decreased quality of life. OBJECTIVES: To assess if an improvement in quality of
      life, as measured by the Skindex-29 and patient-reported itch and pain on a 10
      point visual analogue scale (VAS), correlated with an improvement in cutaneous DM
      disease activity. METHODS: Patients with a completed cutaneous DM disease area
      and severity index [Cutaneous Dermatomyositis Disease Area and Severity Index
      (CDASI)] at two visits separated by at least 2 months were classified into
      responder (n = 15) and nonresponder (n = 30) groups according to the point change
      in the CDASI activity scores between visits. Responders had at least a four-point
      improvement in CDASI activity, indicating clinically relevant improvement.
      RESULTS: The change from baseline to the follow-up visit of the Skindex-29
      subscale scores for the responders vs. the nonresponders were significantly
      different for emotions (P < 0.01), functioning (P < 0.01) and symptoms (P <
      0.01). The change in VAS score between responders and nonresponders was also
      significant for itch (P = 0.01) and pain (P = 0.04). There was no significant
      difference between the groups in terms of disease subtype, sex, race, age,
      treatment for DM, smoking history or a history of malignancy within 5 years of a
      diagnosis of DM. CONCLUSIONS: This is the first study to demonstrate that the
      quality of life of patients with DM improved as their cutaneous disease activity
      decreased.

PMID- 24909748
TI  - Enhancement of extraplastidic oil synthesis in Chlamydomonas reinhardtii using a
      type-2 diacylglycerol acyltransferase with a phosphorus starvation-inducible
      promoter.
AB  - When cultivated under stress conditions, many plants and algae accumulate oil.
      The unicellular green microalga Chlamydomonas reinhardtii accumulates neutral
      lipids (triacylglycerols; TAGs) during nutrient stress conditions. Temporal
      changes in TAG levels in nitrogen (N)- and phosphorus (P)-starved cells were
      examined to compare the effects of nutrient depletion on TAG accumulation in C.
      reinhardtii. TAG accumulation and fatty acid composition were substantially
      changed depending on the cultivation stage before nutrient starvation. Profiles
      of TAG accumulation also differed between N and P starvation. Logarithmic-growth
      phase cells diluted into fresh medium showed substantial TAG accumulation with
      both N and P deprivation. N deprivation induced formation of oil droplets
      concomitant with the breakdown of thylakoid membranes. In contrast, P deprivation
      substantially induced accumulation of oil droplets in the cytosol and maintaining
      thylakoid membranes. As a consequence, P limitation accumulated more TAG both per
      cell and per culture medium under these conditions. To enhance oil accumulation
      under P deprivation, we constructed a P deprivation-dependent overexpressor of a
      Chlamydomonas type-2 diacylglycerol acyl-CoA acyltransferase (DGTT4) using a
      sulphoquinovosyldiacylglycerol 2 (SQD2) promoter, which was up-regulated during P
      starvation. The transformant strongly enhanced TAG accumulation with a slight
      increase in 18 : 1 content, which is a preferred substrate of DGTT4. These
      results demonstrated enhanced TAG accumulation using a P starvation-inducible
      promoter. 

PMID- 24909750
TI  - Polycystic ovary syndrome: a common hormonal condition with major metabolic
      sequelae that physicians should know about.
AB  - Polycystic ovary syndrome (PCOS) is a prevalent, chronic and heterogeneous
      endocrine condition, with reproductive, metabolic and psychological features.
      Insulin resistance and hyperandrogenaemia are the key pathophysiological hormonal
      abnormalities. Insulin resistance is a significant contributor to the
      reproductive and metabolic complications of PCOS, both independently and in the
      setting of excess bodyweight. While the diagnostic criteria are now
      internationally uniformly accepted, individual components of the criteria are ill
      defined, making diagnosis challenging. This, along with low awareness of PCOS,
      has resulted in a significant proportion of women remaining undiagnosed. While
      reproductive features are best recognised in PCOS and form the basis of the
      diagnostic criteria, awareness of psychological and metabolic features,
      recommended screening protocols, and management strategies to prevent metabolic
      complications are important. In this review, we focus on diagnostic criteria, and
      reproductive, metabolic and psychological features of PCOS, as well as
      recommended screening and management strategies suggested by national and
      international evidence-based guidelines. 

PMID- 24909749
TI  - Endoplasmic reticulum stress response in yeast and humans.
AB  - Stress pathways monitor intracellular systems and deploy a range of regulatory
      mechanisms in response to stress. One of the best-characterized pathways, the UPR
      (unfolded protein response), is an intracellular signal transduction pathway that
      monitors ER (endoplasmic reticulum) homoeostasis. Its activation is required to
      alleviate the effects of ER stress and is highly conserved from yeast to human.
      Although metazoans have three UPR outputs, yeast cells rely exclusively on the
      Ire1 (inositol-requiring enzyme-1) pathway, which is conserved in all Eukaryotes.
      In general, the UPR program activates hundreds of genes to alleviate ER stress
      but it can lead to apoptosis if the system fails to restore homoeostasis. In this
      review, we summarize the major advances in understanding the response to ER
      stress in Sc (Saccharomyces cerevisiae), Sp (Schizosaccharomyces pombe) and
      humans. The contribution of solved protein structures to a better understanding
      of the UPR pathway is discussed. Finally, we cover the interplay of ER stress in
      the development of diseases. 

PMID- 24909751
TI  - Characterization of the kidney transcriptome of the South American olive mouse
      Abrothrix olivacea.
AB  - BACKGROUND: The olive mouse Abrothrix olivacea is a cricetid rodent of the
      subfamily Sigmodontinae that inhabits a wide range of contrasting environments in
      southern South America, from aridlands to temperate rainforests. Along its
      distribution, it presents different geographic forms that make the olive mouse a
      good focal case for the study of geographical variation in response to
      environmental variation. We chose to characterize the kidney transcriptome
      because this organ has been shown to be associated with multiple physiological
      processes, including water reabsorption. RESULTS: Transcriptomes of thirteen
      kidneys from individuals from Argentina and Chile were sequenced using Illumina
      technology in order to obtain a kidney reference transcriptome. After combining
      the reads produced for each sample, we explored three assembly strategies to
      obtain the best reconstruction of transcripts, TrinityNorm and DigiNorm, which
      include its own normalization algorithms for redundant reads removal, and
      Multireads, which simply consist on the assembly of the joined reads. We found
      that Multireads strategy produces a less fragmented assembly than normalization
      algorithms but recovers fewer number of genes. In general, about 15000 genes were
      annotated, of which almost half had at least one coding sequence reconstructed at
      99% of its length. We also built a list of highly expressed genes, of which
      several are involved in water conservation under laboratory conditions using
      mouse models. CONCLUSION: Based on our assembly results, Trinity's in silico
      normalization is the best algorithm in terms of cost-benefit returns; however,
      our results also indicate that normalization should be avoided if complete or
      nearly complete coding sequences of genes are desired. Given that this work is
      the first to characterize the transcriptome of any member of Sigmodontinae, a
      subfamily of cricetid rodents with about 400 living species, it will provide
      valuable resources for future ecological and evolutionary genomic analyses.

PMID- 24909752
TI  - Near-haploidization significantly associates with oncocytic adrenocortical,
      thyroid, and parathyroid tumors but not with mitochondrial DNA mutations.
AB  - Mitochondrial-rich oncocytic thyroid tumors frequently show near-haploidization
      and endoreduplication (masked haploidization), which manifests as a near
      homozygous genome (NHG). We now extend this investigation to include
      adrenocortical cancer and parathyroid carcinoma (PaTC), which we studied for a
      NHG in association with mitochondrial DNA mutations. Sixty endocrine tumors from
      59 patients were studied, including 46 thyroid tumor samples of varying
      histology, 11 adrenocortical cancers, and 3 PaTCs. Genome-wide SNP array analysis
      and DNA content analysis were combined to determine the chromosomal dosage
      (allelic state). The entire mitochondrial genome was also studied for mutations.
      In addition, tumors were characterized for somatic mutations in a subset of genes
      that are directly or indirectly implicated in cellular metabolism. In addition to
      a subset of thyroid cancers (n = 5), a NHG was also observed in 1 of 3 PaTCs and
      6 of 11 adrenocortical cancers. All but one of the tumors with a NHG (n = 12)
      showed oncocytic metaplasia (P = 0.0001, two-tailed Fisher's exact). One or more
      damaging or disrupting mtDNA mutations were found in 68% (41/60) of tumor
      samples. No correlation was found between mtDNA mutations and the oncocytic
      phenotype or a NHG, and none of the mutations in nuclear encoded genes correlated
      with the oncocytic phenotype or a NHG. A subset of oncocytic tumors of the
      thyroid, parathyroid, and adrenocortical carcinomas carries a NHG. Although
      damaging/disrupting mtDNA mutations are frequently found in oncocytic and
      nononcocytic endocrine tumors, neither correlates with a NHG phenotype nor with
      an oncocytic phenotype.

PMID- 24909753
TI  - Structure elucidation and biological activity of two new trichothecenes from an
      endophyte, Myrothecium roridum.
AB  - Worldwide, many different grains are infected by various fungi that may produce
      trichothecene mycotoxins. Fungi that produce trichothecenes, as well as the
      trichothecenes themselves, are potential problems for public health. On the other
      hand, trichothecenes possess multiple biological activities. Reduced toxicity may
      result in their applications in the pharmaceutical field. Two new trichothecenes
      along with seven known trichothecenes were isolated from an endophyte of the herb
      plant Ajuga decumbens. Their structures were deduced from 1D and 2D NMR data. The
      results of MTT assays revealed that new trichothecene 2',3'-epoxymyrothecine A,
      1, and myrothecine A, 3, exhibited much lower toxicity compared to other
      trichothecenes. New trichothecene 2',3'-epoxymyrothecine A, 1, could induce
      phosphorylation of JNK (c-Jun N-terminal protein kinase) protein and the PARP
      (poly ADP-ribose polymerase) cleavage, and eventually induce apoptosis in cancer
      cells. These results point out the possibility for application of trichothecenes
      as chemotherapeutic agent. 

PMID- 24909754
TI  - Immunoproteomic analysis of antibody response to cell wall-associated proteins of
      Candida tropicalis.
AB  - AIMS: This study was conducted to identify antigenic proteins of Candida
      tropicalis that are targeted by the host immune system. METHODS AND RESULTS: An
      immunoproteomic approach was used to discover antigens from cell wall of C.
      tropicalis that were recognized by sera from experimentally infected mice. This
      resulted in the identification of twelve distinct proteins, of which ten have
      been previously reported as antigens of Candida albicans. For the remaining two
      proteins, Idh2p has been described as an antigen of Candida parapsilosis, whereas
      Kgd2p is revealed for the first time as an antigenic protein for Candida species.
      These two antigens were expressed as recombinant proteins in Escherichia coli and
      were shown to be specifically recognized by sera from infected host on Western
      blot. CONCLUSIONS: The present work investigated immunoproteome of C. tropicalis
      and identified several biomarker candidate antigens, with Kgd2p as a novel
      immunogenic protein that could be associated with pathogenesis of C. tropicalis.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Findings from this study help to improve
      current understanding on host response to C. tropicalis infection and provide new
      insights into immune-pathogenesis of C. tropicalis. Besides, the immunogenic
      proteins could be considered as targets for the development of immunodiagnostic
      assay and/or vaccine.

PMID- 24909755
TI  - Terrestrial gross primary production inferred from satellite fluorescence and
      vegetation models.
AB  - Determining the spatial and temporal distribution of terrestrial gross primary
      production (GPP) is a critical step in closing the Earth's carbon budget.
      Dynamical global vegetation models (DGVMs) provide mechanistic insight into GPP
      variability but diverge in predicting the response to climate in poorly
      investigated regions. Recent advances in the remote sensing of solar-induced
      chlorophyll fluorescence (SIF) opens up a new possibility to provide direct
      global observational constraints for GPP. Here, we apply an optimal estimation
      approach to infer the global distribution of GPP from an ensemble of eight DGVMs
      constrained by global measurements of SIF from the Greenhouse Gases Observing
      SATellite (GOSAT). These estimates are compared to flux tower data in N. America,
      Europe, and tropical S. America, with careful consideration of scale differences
      between models, GOSAT, and flux towers. Assimilation of GOSAT SIF with DGVMs
      causes a redistribution of global productivity from northern latitudes to the
      tropics of 7-8 Pg C yr(-1) from 2010 to 2012, with reduced GPP in northern
      forests (~3.6 Pg C yr(-1) ) and enhanced GPP in tropical forests (~3.7 Pg C yr(
      1) ). This leads to improvements in the structure of the seasonal cycle,
      including earlier dry season GPP loss and enhanced peak-to-trough GPP in tropical
      forests within the Amazon Basin and reduced growing season length in northern
      croplands and deciduous forests. Uncertainty in predicted GPP (estimated from the
      spread of DGVMs) is reduced by 40-70% during peak productivity suggesting the
      assimilation of GOSAT SIF with models is well-suited for benchmarking. We
      conclude that satellite fluorescence augurs a new opportunity to quantify the GPP
      response to climate drivers and the potential to constrain predictions of carbon
      cycle evolution.

PMID- 24909756
TI  - Maladaptation as a source of senescence in habitats variable in space and time.
AB  - In this study, we use a quantitative genetics model of structured populations to
      investigate the evolution of senescence in a variable environment. Adaptation to
      local environments depends on phenotypic traits whose optimal values vary with
      age and with environmental conditions. We study different scenarios of
      environmental heterogeneity, where the environment changes abruptly, gradually,
      or cyclically with time and where the environment is heterogeneous in space with
      different populations connected by migration. The strength of selection decreases
      with age, which predicts slower adaptation of traits expressed late in the life
      cycle, potentially generating stronger senescence in habitats where selection
      changes in space or in time. This prediction is however complicated by the fact
      that the genetic variance also increases with age. Using numerical calculations,
      we found that the rate of senescence is generally increased when the environment
      varies. In particular, migration between different habitats is a source of
      senescence in heterogeneous landscapes. We also show that the rate of senescence
      can vary transiently when the population is not at equilibrium, with possible
      implications for experimental evolution and the study of invasive species. Our
      results highlight the need to study age-specific adaptation, as a changing
      environment can have a different impact on different age classes. 

PMID- 24909757
TI  - Electron transport characteristics of the dimeric 1,4-benzenedithiol junction.
AB  - Understanding the electron transport between single molecules connected through
      weak interaction is of great importance for molecular electronics. In this paper,
      we report measurements of the conductivity of the dimeric 1,4-benzenedithiol
      (BDT) junction using the scanning tunneling microscopy (STM)-based current
      displacement I(s) method. The conductance was measured to be 6.14*10(-6)  G0 , a
      value almost two orders of magnitude lower than that of the monomer BDT junction.
      In control experiments, the probability of junction formation decreased with the
      presence of tris(2-chloroethyl) phosphate (TCEP), a reducing reagent for the
      disulfide bond. According to theoretical computations, the dihedral angle of the
      S?S bond tends to take a perpendicular conformation. This non-conjugated
      structure localizes the electron distribution and accounts for the low
      conductivity of the disulfide linkage. 

PMID- 24909758
TI  - Vascular structure and function in the medial collateral ligament of anterior
      cruciate ligament transected rabbit knees.
AB  - To determine if decreased vascular responsiveness in the medial collateral
      ligament (MCL) of anterior cruciate ligament transected (ACL-t) rabbit knees is
      due to pericyte deficiency associated with angiogenesis. Vascular responses to
      potassium chloride (KCl), phenylephrine, acetylcholine, and sodium nitroprusside
      (SNP) were evaluated in ACL-t rabbit knees (n = 6) and control knees (n = 5)
      using laser speckle perfusion imaging. Ligament degeneration was determined by
      ultrasound imaging. Vascular and pericyte volume were measured using quantitative
      immunohistochemical volumetric analysis using CD31 and alpha-smooth muscle actin
      antibodies with co-localization analysis. Perfusion was increased in the ACL-t
      rabbits 2.5-fold. Responsiveness to phenylephrine, SNP, and acetylcholine was
      significantly decreased in the ACL knee while no change in KCl responses was
      seen. MCL ultrasound imaging revealed decreased collagen organization, increased
      ligament thickness, and increased water content in the ACL-t MCL. Vascular Volume
      was increased fourfold in ACL deficient knees, while pericyte volume to
      endothelial volume was not changed. No difference in CD31 and alpha-SMA co
      localization was found. Blood vessels in the MCL of ACL-t knees do not lack
      smooth muscle. The MCL vasculature can undergo constrictive response to KCl, but
      have impaired receptor mediated responses and impaired nitric oxide signaling.

PMID- 24909759
TI  - Pemphigoid nodularis mimicking nodular prurigo in an immune-suppressed patient
      with rheumatoid arthritis.

PMID- 24909761
TI  - Subjective memory complaints, depressive symptoms and cognition in Parkinson's
      disease patients.
AB  - BACKGROUND AND PURPOSE: The goal of this study was to establish the prevalence of
      subjective memory complaints (SMCs) and depressive symptoms (DS)s and their
      relation to cognitive functioning in patients with Parkinson's disease (PD).
      METHODS: In all, 248 controls and 104 PD patients were included in the study. The
      PD group was subdivided into three PD subtypes with mild cognitive impairment
      (MCI) according to the Petersen criteria and three PD subtypes with MCI according
      to the Litvan criteria. RESULTS: Substantial SMCs were reported by 7.7% of
      controls and 16.3% of the PD patients (P < 0.001). A clinically relevant degree
      of DSs was evident in 16.6% of controls compared with 40.4% in the PD group (P <
      0.001). An analysis of variance revealed a statistically significant difference
      for SMCs across all Petersen groups as well across all Litvan groups. Two-factor
      analyses of variance with the factors cognitive status (MCI subtype) and
      depressive state (depressed versus not depressed) and SMCs as dependent variable
      revealed significant results. CONCLUSIONS: Approximately 15% of PD patients
      seeking help in a movement disorder clinic report significant SMCs, with an
      increasing degree from cognitively healthy PD to PD-MCI. Significant DSs increase
      SMCs across all cognitive status groups.

PMID- 24909760
TI  - A diastereodivergent synthetic strategy for the syntheses of communesin F and
      perophoramidine.
AB  - An efficient, unified, and stereodivergent approach toward communesin F and
      perophoramidine was examined. The C(3) all-carbon quaternary center of an
      oxindole was smoothly constructed by base-promoted indolone-malonate alkylation
      chemistry. The complementary relative stereochemistry of the crucial vicinal
      quaternary centers found in communesin F and perophoramidine was selectively
      installed by substrate-controlled decarboxylative allylic alkylations. 

PMID- 24909762
TI  - Female detection of the synthetic sex pheromone contributes to the efficacy of
      mating disruption of the European grapevine moth, Lobesia botrana.
AB  - BACKGROUND: Studies of the mechanisms by which mating-disruption techniques
      control insect pest populations have traditionally focused on the effects of the
      species-specific sex pheromone on the male moths, while neglecting possible
      direct effects of the pheromone on females. Here, the effects of exposure to
      synthetic species-specific sex-pheromone on Lobesia botrana (European grapevine
      moth) females were tested. RESULTS: Females in vineyards that were treated with
      mating-disruption pheromone burst into short bouts of flying more frequently, but
      called significantly less frequently than females in untreated plots. Reduced
      calling caused by exposure to the species-specific sex-pheromone may increase the
      age at which females mate and thereby reduce female fecundity. Females that
      called in a pheromone-saturated environment experienced a decrease in number of
      oviposited eggs. A further decrease in reproductive success may occur if females
      delay oviposition when exposed to access of the synthetic pheromone. CONCLUSIONS:
      In addition to reducing the ability of males to locate females, the mating
      disruption technique can suppress pest numbers as a consequence of its direct
      effects on females. The two mechanisms probably act synergistically.

PMID- 24909763
TI  - The effect and safety of polylactic acid and adipose-derived stromal vascular
      fraction cell as an injectable bulking agent in urologic field: a 24-week follow
      up study.
AB  - The aim of this study is to evaluate whether polylactic acid (PLA) microspheres
      and adipose-derived stromal vascular fraction (SVF) cells have appropriate
      properties as an injectable bulking agent in urologic field. Forty male Sprague
      Dawley rats (2-week-old) were randomized into two groups. A total of 0.05 mL of
      PLA microsphere suspension and 0.05 mL of PLA microsphere suspension mixed with
      PKH26-labeled SVF cells were injected into bladder wall in group I and group II,
      respectively. At 2, 8, 16, and 24 weeks of PLA microspheres injection, the
      volumes of implants were measured and bladder tissues including implants were
      analyzed and compared grossly and histologically between groups. The distant
      organs were examined histologically to determine migration of PLA microspheres.
      At 24 weeks of implantation, 65-70% of injected volume was maintained and there
      was no significant difference between groups. In histological analyses, injected
      PLA microspheres were localized in muscular layer of bladder without infiltration
      into adjacent layer. From 8 to 16 weeks of injection, hybrid tissues contained
      collagen and actin were observed between PLA microspheres and these findings were
      more clear in group II. PHK26-labeled SVF cells were identified by fluorescence
      microscopy at all time points. There was no migration of PLA microspheres to
      other organs and no abnormality in weight gain and hematologic values. These
      results suggest the possibility of PLA microspheres as a potentially useful
      bulking agent in urologic field. And further investigation is needed to know
      synergic effect of SVF cells.

PMID- 24909764
TI  - Aerosol-stable peptide-coated liposome nanoparticles: a proof-of-concept study
      with opioid fentanyl in enhancing analgesic effects and reducing plasma drug
      exposure.
AB  - Previously, we reported a novel pressurized olfactory drug (POD) delivery device
      that deposits aerosolized drug preferentially to upper nasal cavity. This POD
      device provided sustained central nervous system (CNS) levels of soluble morphine
      analgesic effects. However, analgesic onset of less soluble fentanyl was more
      rapid but brief, likely because of hydrophobic fentanyl redistribution readily
      back to blood. To determine whether fentanyl incorporated into an aerosol-stable
      liposome that binds to nasal epithelial cells will enhance CNS drug exposure and
      analgesic effects and reduce plasma exposure, we constructed Arg-Gly-Asp (RGD)
      liposomes anchored with acylated integrin-binding peptides (palmitoyl-Gly-Arg-Gly
      Asp-Ser). The RGD liposomes, which assume gel phase membrane structure at 25 
      degrees C, were stable under the stress of aerosolization as only 2.2 +/- 0.5%
      calcein leakage was detected. The RGD-mediated integrin binding of liposome is
      also verified to be unaffected by aerosolization. Rats treated with fentanyl in
      RGD liposome and POD device exhibited greater analgesic effect, as compared with
      the free drug counterpart (AUC(effect) = 1387.1% vs. 760.1% MPE*min), whereas
      approximately 20% reduced plasma drug exposure was noted (AUC(0-120) = 208.2 vs.
      284.8 ng min/mL). Collectively, fentanyl incorporated in RGD liposomes is
      physically and biologically stable under aerosolization, enhanced the overall
      analgesic effects, and reduced plasma drug exposure for the first 2 h.

PMID- 24909765
TI  - Agreement between clinical practice and trained central reading in reading of
      sacroiliac joints on plain pelvic radiographs. Results from the DESIR cohort.
AB  - OBJECTIVE: To investigate the degree of agreement between local
      rheumatologists/radiologists and central trained readers (external standard) on
      the presence/absence of sacroiliitis on radiographs of the sacroiliac (SI)
      joints. METHODS: Patients with inflammatory back pain (duration >=3 months but <3
      years) suggestive of axial spondyloarthritis (SpA) were included in the Devenir
      des Spondylarthropathies Indiffererenciees Recentes (DESIR) cohort. Baseline
      radiographs of the SI joints were interpreted by 2 central readers (modified New
      York criteria); cases of disagreement were adjudicated by a third reader,
      yielding a positive or a negative result (central reading). The same radiographs
      were also interpreted by local radiologists/rheumatologists and were rated as
      "normal," "doubtful sacroiliitis," "obvious sacroiliitis," or "SI joint fusion"
      (local reading); positive findings were defined as "at least unilateral obvious
      sacroiliitis," "bilateral obvious sacroiliitis," or "at least unilateral fusion."
      Agreement and misclassifications between central readers and between central
      reading versus local reading were calculated (kappa values). RESULTS: Interreader
      agreement between the central readers was moderate (kappa = 0.54); 108 of 688
      radiographs (15.7%) were adjudicated. According to local reading ("at least
      unilateral obvious sacroiliitis"), 183 of the 688 patients (26.6%) had
      sacroiliitis, whereas according to central reading, 145 of 688 patients (21.1%)
      had sacroiliitis. Agreement between local reading and central reading was also
      moderate (kappa = 0.55); 76 of 183 patients (41.5%) with "at least unilateral
      obvious sacroiliitis" (positive by local reading) and 32 of 109 patients (29.4%)
      with "bilateral obvious sacroiliitis" or "at least unilateral fusion" (positive
      by local reading) were rated as "negative" by central reading, and 38 of 505
      patients (7.5%) and 68 of 579 patients (11.7%), respectively, without
      sacroiliitis (negative by local reading) were interpreted as "positive" by
      central reading. CONCLUSION: In patients with recent-onset inflammatory back
      pain, both trained readers and local rheumatologists/radiologists agreed only
      moderately on the recognition of radiographic sacroiliitis. A significant
      proportion of locally recognized ankylosing spondylitis (AS) patients were not
      confirmed as having AS by central reading (false positive), while a small
      minority of patients were false negative, indicating the necessity of
      reevaluating the role of radiographic sacroiliitis as diagnostic criterion for
      axial SpA.

PMID- 24909766
TI  - Uniaxial movements of a metal-cyanide framework switched by weak interactions
      through dehydration and rehydration.
AB  - A metal-cyanide framework undergoes a dehydration-rehydration triggered
      reversible single-crystal-to-single-crystal transformation. The resulting
      accordion-like contraction-expansion corresponds to a size change along the c
      axis as much as 24 %. This anisotropic response arises from the cooperativity
      among the water molecules, K ions, and CN groups between the unique two
      dimensional bimetallic layers through weak interactions of hydrogen bonds and
      electrostatic (ionic) interactions. The key role of the water molecules in the
      dehydration-rehydration process is revealed by solid-state (1)H NMR spectroscopy
      and dielectric measurements.

PMID- 24909768
TI  - Ultrasensitive enzyme-free immunoassay for squamous cell carcinoma antigen using
      carbon supported Pd-Au as electrocatalytic labels.
AB  - A novel nonenzymatic sandwich-type electrochemical immunosensor has been
      developed to detect squamous cell carcinoma antigen (SCCA). Nitrogen-doped
      graphene sheet (N-GS) was used to increase capacity of capturing primary
      antibodies (Ab1). Carbon-supported Pd-Au binary nanoparticles (Pd-Au/C) were
      synthesized and used to label secondary antibodies (Ab2). The specific binding of
      SCCA and antibodies enabled a quantitative attachment of Pd-Au/C on the electrode
      surface. Electrocatalytic analysis showed that the prepared Pd-Au/C exhibit
      excellent electrocatalytic activity towards hydrogen peroxide (H2O2). We use
      current response of electrocatalytic labels Pd-Au/C to detect the concentration
      of SCCA. The unique nonenzymatic immunosensor exhibits a relatively wide linear
      range from 0.005 to 2 ng mL(-1) and high sensitivity with a low detection limit
      of 1.7 pg mL(-1). The immunsensor also shows good reproducibility (4.2%) and
      stability (5.8%), which makes it an enormous application prospect in clinical
      research.

PMID- 24909767
TI  - An integrated sample pretreatment platform for quantitative N-glycoproteome
      analysis with combination of on-line glycopeptide enrichment, deglycosylation and
      dimethyl labeling.
AB  - Relative quantification of N-glycoproteomes shows great promise for the discovery
      of candidate biomarkers and therapeutic targets. The traditional protocol for
      quantitative analysis of glycoproteomes is usually off-line performed, and
      suffers from long sample preparation time, and the risk of sample loss or
      contamination due to manual manipulation. In this study, a novel integrated
      sample preparation platform for quantitative N-glycoproteome analysis was
      established, with combination of online N-glycopeptide capture by a HILIC column,
      sample buffer exchange by a N2-assisted HILIC-RPLC interface, deglycosylation by
      a hydrophilic PNGase F immobilized enzymatic reactor (hIMER) and solid dimethyl
      labeling on a C18 precolumn. To evaluate the performance of such a platform, two
      equal aliquots of immunoglobulin G (IgG) digests were sequentially pretreated,
      followed by MALDI-TOF MS analysis. The signal intensity ratio of heavy/light
      (H/L) labeled deglycosylated peptides with the equal aliquots was 1.00 (RSD=6.2%,
      n=3), much better than those obtained by the offline protocol, with H/L ratio as
      0.76 (RSD=11.6%, n=3). Additionally, the total on-line sample preparation time
      was greatly shortened to 160 min, much faster than that of offline approach
      (24h). Furthermore, such an integrated pretreatment platform was successfully
      applied to analyze the two kinds of hepatocarcinoma ascites syngeneic cell lines
      with high (Hca-F) and low (Hca-P) lymph node metastasis rates. For H/L labeled
      Hca-P lysates with the equal aliquots, 99.6% of log2 ratios (H/L) of quantified
      glycopeptides ranged from -1 to 1, demonstrating high accuracy of the developed
      sample preparation strategy. By triplicated analysis of glycopeptides and non
      glycopeptides of Hca-F and Hca-P lysates, 43 up-regulated and 30 down-regulated
      (Hca-F/P) N-glycosylation sites, and 11 significantly changed N-glycoproteins
      were successfully quantified, and most of them were related to tumorigenesis and
      tumor metastasis. All these results demonstrate the developed integrated N
      glycoprotein pretreatment platform is of great power for the accurate, precise
      and high-throughput analysis of N-glycoproteomes.

PMID- 24909769
TI  - Speciation of chromium using chronoamperometric biosensors based on screen
      printed electrodes.
AB  - Chronoamperometric assays based on tyrosinase and glucose oxidase (GOx)
      inactivation have been developed for the monitoring of Cr(III) and Cr(VI).
      Tyrosinase was immobilized by crosslinking on screen-printed carbon electrodes
      (SPCEs) containing tetrathiafulvalene (TTF) as electron transfer mediator. The
      tyrosinase/SPC(TTF)E response to pyrocatechol is inhibited by Cr(III). This
      process, that is not affected by Cr(VI), allows the determination of Cr(III) with
      a capability of detection of 2.0+/-0.2 MUM and a reproducibility of 5.5%. GOx
      modified screen-printed carbon platinised electrodes (SPCPtEs) were developed for
      the selective determination of Cr(VI) using ferricyanide as redox mediator. The
      biosensor was able to discriminate two different oxidation states of chromium
      being able to reject Cr(III) and to detect the toxic species Cr(VI).
      Chronoamperometric response of the biosensor towards glucose decreases with the
      presence of Cr(VI), with a capability of detection of 90.5+/-7.6 nM and a
      reproducibility of 6.2%. A bipotentiostatic chronoamperometric biosensor was
      finally developed using a tyrosinase/SPC(TTF)E and a GOx/SPC(Pt)E connected in
      array mode for the simultaneous determination of Cr(III) and Cr(VI) in spiked tap
      water and in waste water from a tannery factory samples.

PMID- 24909770
TI  - Electrodeposited nitrogen-doped graphene/carbon nanotubes nanocomposite as
      enhancer for simultaneous and sensitive voltammetric determination of caffeine
      and vanillin.
AB  - A nitrogen-doped graphene/carbon nanotubes (NGR-NCNTs) nanocomposite was employed
      into the study of the electrochemical sensor via electrodeposition for the first
      time. The morphology and structure of NGR-NCNTs nanocomposite were investigated
      by scanning electron microscopy (SEM) and transmission electron microscopy (TEM),
      respectively. Meanwhile, the electrochemical performance of the glassy carbon
      electrode (GCE) modified with electrodeposited NGR-NCNTs (ENGR-NCNTs/GCE) towards
      caffeine (CAF) and vanillin (VAN) determination was demonstrated by cyclic
      voltammetry (CV) and square wave voltammetry (SWV). Under optimal condition, ENGR
      NCNTs/GCE exhibited a wide linearity of 0.06-50 MUM for CAF and 0.01-10 MUM for
      VAN with detection limits of 0.02 MUM and 3.3*10(-3) MUM, respectively.
      Furthermore, the application of the proposed sensor in food products was proven
      to be practical and reliable. The desirable results show that the ENGR-NCNTs
      nanocomposite has promising potential in electrocatalytic biosensor application.

PMID- 24909771
TI  - Synergistic effect of the simultaneous chemometric analysis of 1H NMR
      spectroscopic and stable isotope (SNIF-NMR, 18O, 13C) data: application to wine
      analysis.
AB  - It is known that (1)H NMR spectroscopy represents a good tool for predicting the
      grape variety, the geographical origin, and the year of vintage of wine. In the
      present study we have shown that classification models can be improved when (1)H
      NMR profiles are fused with stable isotope (SNIF-NMR, (18)O, (13)C) data.
      Variable selection based on clustering of latent variables was performed on (1)H
      NMR data. Afterwards, the combined data of 718 wine samples from Germany were
      analyzed using linear discriminant analysis (LDA), partial least squares
      discriminant analysis (PLS-DA), factorial discriminant analysis (FDA) and
      independent components analysis (ICA). Moreover, several specialized multiblock
      methods (common components and specific weights analysis (ComDim), consensus PCA
      and consensus PLS-DA) were applied to the data. The best improvement in
      comparison with (1)H NMR data was obtained for prediction of the geographical
      origin (up to 100% for the fused data, whereas stable isotope data resulted only
      in 60-70% correct prediction and (1)H NMR data alone in 82-89% respectively).
      Certain enhancement was obtained also for the year of vintage (from 88 to 97% for
      (1)H NMR to 99% for the fused data), whereas in case of grape varieties improved
      models were not obtained. The combination of (1)H NMR data with stable isotope
      data improves efficiency of classification models for geographical origin and
      vintage of wine and can be potentially used for other food products as well. 

PMID- 24909772
TI  - Universal fluorescent tri-probe ligation equipped with capillary electrophoresis
      for targeting SMN1 and SMN2 genes in diagnosis of spinal muscular atrophy.
AB  - This is the first ligase chain reaction used for diagnosis of spinal muscular
      atrophy (SMA). Universal fluorescent tri-probe ligation (UFTPL), a novel strategy
      used for distinguishing the multi-nucleotide alternations at single base, is
      developed to quantitatively analyze the SMN1/SMN2 genes in diagnosis of SMA.
      Ligase chain reaction was performed by adding three probes including universal
      fluorescent probe, connecting probe and recognizing probe to differentiate single
      nucleotide polymorphisms in UFTPL. Our approach was based on the two UFTPL
      products of survival motor neuron 1 (SMN1) and SMN2 genes (the difference of 9
      mer) and analyzed by capillary electrophoresis (CE). We successfully determined
      various gene dosages of SMN1 and SMN2 genes in homologous or heterologous
      subjects. By using the UFTPL-CE method, the SMN1 and SMN2 genes were fully
      resolved with the resolution of 2.16+/-0.37 (n=3). The r values of SMN1 and SMN2
      regression curves over a range of 1-4 copies were above 0.9944. Of the 48 DNA
      samples, the data of gene dosages were corresponding to that analyzed by
      conformation sensitive CE and denatured high-performance liquid chromatography
      (DHPLC). This technique was found to be a good methodology for quantification or
      determination of the relative genes having multi-nucleotide variants at single
      base. 

PMID- 24909773
TI  - Preparation and chromatographic evaluation of new branch-type diamide-embedded
      octadecyl stationary phase with enhanced shape selectivity.
AB  - A novel branch-type diamide-embedded octadecyl stationary phase was prepared by
      facile amidation. The preparation of this new phase involves the synthesis of new
      bifunctional silane ligand and surface modification of spherical silica via
      anchoring of silane coupling agent. The obtained diamide-embedded octadecyl
      stationary phase demonstrated excellent hydrophobic selectivity, as well as
      enhanced shape and planarity selectivity in comparison to commercial polymeric
      and monomeric C18 phases, respectively, as revealed by the systematic
      investigation into its liquid chromatographic retention of isomeric polycyclic
      aromatic hydrocarbons. The applicability of this new stationary phase was further
      testified by the effective separation of isomeric compounds belong to different
      chemical classes, including chain isomers of alkylbenzenes, and positional
      isomers of substituted aromatics. An in-depth analysis of the separation
      mechanisms other than molecular shape recognition involved in the new stationary
      phase was performed using a linear solvation energy relationships model and
      compared with its monoamide and pure C18 counterparts correspondingly. The
      performance of the new stationary phase in quantitative analysis of phenols from
      real-world samples was also evaluated. 

PMID- 24909774
TI  - The value of the "suspicious for urothelial carcinoma" cytology category: a
      correlative study of 4 years including 337 patients.
AB  - BACKGROUND: The terminology used in reporting urine cytology lacks uniformity and
      the significance of the "atypical" and "suspicious" categories is still not well
      established. This results in variable clinical follow-up and management of those
      cases. The authors sought to investigate the prognostic value of a diagnosis of
      "suspicious for high-grade urothelial carcinoma" (HGUCA). METHODS: All cases with
      a "suspicious" or "positive" cytological diagnosis spanning 4 years were included
      and correlated with the subsequent biopsies obtained within 6 months of urine
      collection. RESULTS: A total of 447 correlative events (57% positive and 43%
      suspicious) corresponding to 773 cytology specimens and 337 patients were
      included. The morphology of the "suspicious" cells was similar to what has
      recently been reported in the literature as "atypical urothelial cells, cannot
      exclude HGUCA." A "suspicious" diagnosis was more often rendered than a
      "positive" one in voided specimens (80% vs 65%, respectively). The mean interval
      between cytology and biopsy was 31 days. On follow-up, 92% of "suspicious"
      diagnoses (176 of 191 diagnoses) and 90% of "positive" diagnoses (230 of 256
      diagnoses) were found to have a biopsy with a diagnosis of carcinoma (low grade
      or high grade). A diagnosis of HGUCA followed a "suspicious" and a "positive"
      diagnosis in 79% and 86% of cases, respectively. CONCLUSIONS: A "suspicious"
      diagnosis as defined in the current study warrants close investigations and
      repeat biopsy to rule out HGUCA. In addition, the findings of the current study
      raise the question of the need for quantitative criteria for diagnosing HGUCA on
      cytology.

PMID- 24909775
TI  - Getting ahead: forward models and their place in cognitive architecture.
AB  - The use of forward models (mechanisms that predict the future state of a system)
      is well established in cognitive and computational neuroscience. We compare and
      contrast two recent, but interestingly divergent, accounts of the place of
      forward models in the human cognitive architecture. On the Auxiliary Forward
      Model (AFM) account, forward models are special-purpose prediction mechanisms
      implemented by additional circuitry distinct from core mechanisms of perception
      and action. On the Integral Forward Model (IFM) account, forward models lie at
      the heart of all forms of perception and action. We compare these neighbouring
      but importantly different visions and consider their implications for the
      cognitive sciences. We end by asking what kinds of empirical research might offer
      evidence favouring one or the other of these approaches. 

PMID- 24909776
TI  - Fusarium species, chemotype characterisation and trichothecene contamination of
      durum and soft wheat in an area of central Italy.
AB  - BACKGROUND: Fusarium head blight (FHB) of wheat is an important disease causing
      yield losses and mycotoxin contamination. The aim of the work was to detect and
      characterise trichothecene producing Fusarium species in durum and soft wheat
      cultivated in an area of central Italy in 2009 and 2010 and to determine
      trichothecene contamination by LC-MS/MS in the grain. RESULTS: F. graminearum s.
      str. was the most frequent species. In 2009, the occurrence of F. avenaceum and
      F. poae was higher than in 2010. Among F. graminearum strains, the 15-acetyl
      deoxynivalenol (15-ADON) chemotype could be found more frequently, followed by
      nivalenol (NIV) and 3-ADON chemotypes, while all F. culmorum isolates belonged to
      the 3-ADON chemotype. All F. poae strains were NIV chemotypes. In vitro
      trichothecene production confirmed molecular characterisation. Durum wheat was
      characterised by a higher average DON contamination with respect to soft wheat,
      NIV was always detected at appreciable levels while type-A trichothecenes were
      mostly found in durum wheat samples in 2009 with 6% of samples exceeding the
      contamination level recently recommended by the European Union. CONCLUSION:
      Climatic conditions were confirmed to be predominant factors influencing
      mycotoxigenic species composition and mycotoxin contaminations. However, NIV
      contamination was found to occur irrespective of climatic conditions, suggesting
      that it may often represent an under-estimated risk to be further investigated.

PMID- 24909777
TI  - Insights into the structural basis of 3,5-diaminoindazoles as CDK2 inhibitors:
      prediction of binding modes and potency by QM-MM interaction, MESP and MD
      simulation.
AB  - The novel 3,5-diaminoindazole derivatives are well-known as potent and anti
      proliferative cyclin-dependent kinase 2 inhibitors. We report a combined quantum
      mechanics/molecular mechanics study to determine the protein-ligand interaction
      energy, and some quantum chemical descriptors to successfully rank these
      inhibitors. The results in this work show that the QM-MM interaction energy is
      strongly correlated to the biological activity and can be used as a predictor,
      which was further validated by Spearman's rank correlation coefficient. An
      exhaustive analysis of the protein-ligand structures obtained from molecular
      dynamics simulations shows specific interactions within the active site.
      Furthermore, the docking study was supported by electronic property analysis
      using density functional theory at the B3LYP/3-21*G level. The results obtained
      from molecular docking and surface analysis shed some insight on steric and
      electronic complementarities of these molecules to CDK2. Aqueous solvation energy
      values give an indication of the solubility and can be used as a guide for the
      pharmacokinetic optimization of these molecules. Furthermore, ADME/T properties
      calculated are in the desirable range, so these compounds are predicted to be
      drug like with low toxicity potential. Overall, the approach was successful in
      the cases considered, and it could be useful for the design of inhibitors in the
      lead optimization phase of drug discovery against CDK2. 

PMID- 24909778
TI  - Magnetic, superhydrophobic and durable silicone sponges and their applications in
      removal of organic pollutants from water.
AB  - Porous silicone sponges are fabricated by polymerization of organosilanes in the
      presence of Fe3O4@silica nanoparticles. The sponges feature fast magnetic
      responsivity, superhydrophobicity/superoleophilicity, high compressibility and
      stability. The sponges can selectively absorb floating oils on a water surface,
      heavy oils under water and even emulsified oils. 

PMID- 24909779
TI  - Gain in toxic function of stefin B EPM1 mutants aggregates: correlation between
      cell death, aggregate number/size and oxidative stress.
AB  - EPM1 is a rare progressive myoclonus epilepsy accompanied by apoptosis in the
      cerebellum of patients. Mutations in the gene of stefin B (cystatin B) are
      responsible for the primary defect underlying EPM1. Taking stefin B aggregates as
      a model we asked what comes first, protein aggregation or oxidative stress, and
      how these two processes correlate with cell death. We studied the aggregation in
      cells of the stefin B wild type, G4R mutant, and R68X fragment before (Ceru et
      al., 2010, Biol. Cell). The present study was performed on two more missense
      mutants of human stefin B, G50E and Q71P, and they similarly showed numerous
      aggregates upon overexpression. Mutant- and oligomer-dependent increase in
      oxidative stress and cell death in cells bearing aggregates was shown. On the
      other hand, there was no correlation between the size and number of the
      aggregates and cell death. We suggest that differences in toxicity of the
      aggregates depend on whether they are in oligomeric/protofibrillar or fibrillar
      form. This in turn likely depends on the mutant's 3D structure where unfolded
      proteins show lower toxicity. Imaging by transmission electron microscopy showed
      that the aggregates in cells are of different types: bigger perinuclear,
      surrounded by membranes and sometimes showing vesicle-like invaginations, or
      smaller, punctual and dispersed throughout the cytoplasm. All EPM1 mutants
      studied were inactive as cysteine proteases inhibitors and in this way contribute
      to loss of stefin B functions. Relevance to EPM1 disease by gain in toxic
      function is discussed. 

PMID- 24909780
TI  - Building resiliency: a cross-sectional study examining relationships among health
      related quality of life, well-being, and disaster preparedness.
AB  - BACKGROUND: Worldwide, disaster exposure and consequences are rising. Disaster
      risk in New Zealand is amplified by island geography, isolation, and ubiquitous
      natural hazards. Wellington, the capital city, has vital needs for evacuation
      preparedness and resilience to the devastating impacts and increasing
      uncertainties of earthquake and tsunami disasters. While poor quality of life
      (QoL) is widely-associated with low levels of engagement in many health
      protective behaviors, the relationships among health-related quality of life
      (HrQoL), well-being, and preparedness are virtually unknown. METHODS: We
      hypothesized that QoL and well-being affect household evacuation preparedness. We
      performed a quantitative epidemiologic survey (cross-sectional design) of
      Wellington adults. Our investigation assessed health-promoting attributes that
      build resiliency, conceptualized as health-protective attitudes and behaviors.
      Multidimensional QoL variables were measured using validated psychometric scales
      and analyzed for associations with evacuation preparedness, and we determined
      whether age and gender affected these relationships. RESULTS: We received 695
      survey responses (28.5% response rate; margin of error +/-3.8%; 80% statistical
      power to detect true correlations of 0.11 or greater). Correlational analyses
      showed statistically significant positive associations with evacuation
      preparedness for spiritual well-being, emotional well-being, and life
      satisfaction. No associations were found for mental health, social well-being, or
      gender; physical health was weakly negatively associated. Evacuation preparedness
      increased with age. Regression analyses showed that overall health and well-being
      explained 4.6-6.8% of the variance in evacuation preparedness. Spiritual well
      being was the only QoL variable that significantly and uniquely explained
      variance in preparedness. CONCLUSIONS: How well-being influences preparedness is
      complex and deeply personal. The data indicate that multidimensional readiness is
      essential, and meaningfulness is an important factor. Inadequate levels of
      tangible preparedness actions are accompanied by gaps in intangible readiness
      aspects, such as: 1) errors in perceived exposure to and salience of natural
      hazards, yielding circumscribed risk assessments; 2) unfamiliarity with the scope
      and span of preparedness; 3) underestimating disaster consequences; and 4)
      misinterpreting the personal resources required for self-managing disaster and
      uncertainty. Our results highlight that conceptualizing preparedness to include
      attitudes and behaviors of readiness, integrating well-being and meaningfulness
      into preparedness strategies, and prioritizing evacuation planning are critical
      for resiliency as a dynamic process and outcome.

PMID- 24909781
TI  - Increased association of the ERG oncoprotein expression in advanced stages of
      prostate cancer in Filipinos.
AB  - BACKGROUND: Filipinos with prostate cancer (CaP) are at increased risk of
      harboring advanced stages and lower survival rates compared to other Asians. This
      study aims to investigate prevalence of ETS-related gene (ERG) oncoprotein
      overexpression in Filipinos as surrogate of TMPRSS2-ERG gene fusions, using a
      highly specific monoclonal antibody (ERG-MAb), and conduct the first attempt to
      study the role of genetic alterations in the aggressive tumor biologic behaviour
      of CaP among Filipinos. METHODS: This case-matched, case-control retrospective
      study evaluated ERG expression in Filipino patients diagnosed with CaP and its
      effect on stage and Gleason grade of their disease. Men who underwent radical
      prostatectomy for organ-confined disease at the University of the Philippines
      Philippine General Hospital (UP-PGH) comprised the organ-confined cohort. Age
      matched adults who had trans-rectal ultrasound-guided prostate (TRUSP) biopsy or
      trans-urethral resection of the prostate (TURP) with bilateral orchiectomy for T4
      or stage IV CaP composed the advanced disease cohort. RESULTS: Overall ERG
      expression frequency of 23.08% (N = 104) was demonstrated, with a higher rate
      observed in the advanced disease cohort (32.69%) compared to the organ-confined
      group (13.46%). Furthermore, ERG overexpression was only detected among
      intermediate and high-risk tumors. A high-specificity (98.08%) of the ERG-MAb for
      malignant prostatic cells was likewise demonstrated. CONCLUSIONS: In contrast to
      higher ERG frequency in Western countries, it is much lower in Filipino CaP,
      which is similar to lower rates noted from other Asian countries. The 98.08%
      specificity of ERG oncoprotein for prostate tumor cells combined with its
      increased association in advanced disease, suggests for prognostic potential of
      ERG that may aid clinicians in treatment decisions for Filipino CaP patients.

PMID- 24909782
TI  - Single-molecule kinetics of the eukaryotic initiation factor 4AI upon RNA
      unwinding.
AB  - The eukaryotic translation initiation factor 4AI (eIF4AI) is the prototypical
      DEAD-box RNA helicase. It has a "dumbbell" structure consisting of two domains
      connected by a flexible linker. Previous studies demonstrated that eIF4AI, in
      conjunction with eIF4H, bind to loop structures and repetitively unwind RNA
      hairpins. Here, we probe the conformational dynamics of eIF4AI in real time using
      single-molecule FRET. We demonstrate that eIF4AI/eIF4H complex can repetitively
      unwind RNA hairpins by transitioning between an eIF4AI "open" and a "closed"
      conformation using the energy derived from ATP hydrolysis. Our experiments
      directly track the conformational changes in the catalytic cycle of eIF4AI and
      eIF4H, and this correlates precisely with the kinetics of RNA unwinding.
      Furthermore, we show that the small-molecule eIF4A inhibitor hippuristanol locks
      eIF4AI in the closed conformation, thus efficiently inhibiting RNA unwinding.
      These results indicate that the large conformational changes undertaken by eIF4A
      during the helicase catalytic cycle are rate limiting.

PMID- 24909785
TI  - Hollow magnetic microspheres obtained by nanoparticle adsorption on surfactant
      stabilized microbubbles.
AB  - We report on the stabilization of nanoparticle-decorated microbubbles for long
      periods of time using a synergism between a soluble surfactant and nanoparticles.
      The soluble surfactant is the perfluoroalkyl phosphate C8F17(CH2)2OP(O)(OH)2
      (labeled F8H2Phos) and the nanoparticles (NPs) are 20-25 nm cobalt ferrite
      (CoFe2O4). The NP-F8H2Phos system has been studied by dynamic light scattering,
      dynamic magnetic susceptibility measurements and thermal gravimetric analysis.
      Microbubbles with diameters in the 1-20 MUm range have been stabilized in 0.1 M
      NaCl brine. Its presence is crucial for the long-term stabilization. The
      surfactant adsorbs rapidly on bubbles and slows down the bubble shrinkage. Thus,
      the NPs can attach to the bubble and form a hollow sphere with a rigid shell. The
      charge screening by NaCl favors the attachment of NPs to the bubble surface. The
      coverage of the bubbles by the CoFe2O4 nanoparticle layer is confirmed by
      thermally induced inflation-deflation experiments and the control of bubbles with
      a magnetic field. 

PMID- 24909783
TI  - Influence of domain interactions on conformational mobility of the progesterone
      receptor detected by hydrogen/deuterium exchange mass spectrometry.
AB  - Structural and functional details of the N-terminal activation function 1 (AF1)
      of most nuclear receptors are poorly understood due to the highly dynamic
      intrinsically disordered nature of this domain. A hydrogen/deuterium exchange
      (HDX) mass-spectrometry-based investigation of TATA box-binding protein (TBP)
      interaction with various domains of progesterone receptor (PR) demonstrate that
      agonist-bound PR interaction with TBP via AF1 impacts the mobility of the C
      terminal AF2. Results from HDX and other biophysical studies involving agonist-
      and antagonist-bound full-length PR and isolated PR domains reveal the molecular
      mechanism underlying synergistic transcriptional activation mediated by AF1 and
      AF2, dominance of PR-B isoform over PR-A, and the necessity of AF2 for full AF1
      mediated transcriptional activity. These results provide a comprehensive picture
      elaborating the underlying mechanism of PR-TBP interactions as a model for
      studying nuclear receptor (NR)-transcription factor functional interactions.

PMID- 24909784
TI  - Structure of the LdcB LD-carboxypeptidase reveals the molecular basis of
      peptidoglycan recognition.
AB  - Peptidoglycan surrounds the bacterial cytoplasmic membrane to protect the cell
      against osmolysis. The biosynthesis of peptidoglycan, made of glycan strands
      crosslinked by short peptides, is the target of antibiotics like beta-lactams and
      glycopeptides. Nascent peptidoglycan contains pentapeptides that are trimmed by
      carboxypeptidases to tetra- and tripeptides. The well-characterized DD
      carboxypeptidases hydrolyze the terminal D-alanine from the stem pentapeptide to
      produce a tetrapeptide. However, few LD-carboxypeptidases that produce
      tripeptides have been identified, and nothing is known about substrate
      specificity in these enzymes. We report biochemical properties and crystal
      structures of the LD-carboxypeptidases LdcB from Streptococcus pneumoniae,
      Bacillus anthracis, and Bacillus subtilis. The enzymes are active against
      bacterial cell wall tetrapeptides and adopt a zinc-carboxypeptidase fold
      characteristic of the LAS superfamily. We have also solved the structure of S.
      pneumoniae LdcB with a product mimic, elucidating the residues essential for
      peptidoglycan recognition and the conformational changes that occur on ligand
      binding.

PMID- 24909786
TI  - Computer aided detection system for micro calcifications in digital mammograms.
AB  - Breast cancer continues to be a significant public health problem in the world.
      Early detection is the key for improving breast cancer prognosis. Mammogram
      breast X-ray is considered the most reliable method in early detection of breast
      cancer. However, it is difficult for radiologists to provide both accurate and
      uniform evaluation for the enormous mammograms generated in widespread screening.
      Micro calcification clusters (MCCs) and masses are the two most important signs
      for the breast cancer, and their automated detection is very valuable for early
      breast cancer diagnosis. The main objective is to discuss the computer-aided
      detection system that has been proposed to assist the radiologists in detecting
      the specific abnormalities and improving the diagnostic accuracy in making the
      diagnostic decisions by applying techniques splits into three-steps procedure
      beginning with enhancement by using Histogram equalization (HE) and Morphological
      Enhancement, followed by segmentation based on Otsu's threshold the region of
      interest for the identification of micro calcifications and mass lesions, and at
      last classification stage, which classify between normal and micro calcifications
      'patterns and then classify between benign and malignant micro calcifications. In
      classification stage; three methods were used, the voting K-Nearest Neighbor
      classifier (K-NN) with prediction accuracy of 73%, Support Vector Machine
      classifier (SVM) with prediction accuracy of 83%, and Artificial Neural Network
      classifier (ANN) with prediction accuracy of 77%. 

PMID- 24909788
TI  - Hope for Huntington's disease? A novel approach for disease modification.

PMID- 24909787
TI  - Intensive residential treatment for severe obsessive-compulsive disorder:
      characterizing treatment course and predictors of response.
AB  - BACKGROUND: Intensive residential treatment (IRT) is effective for severe,
      treatment-resistant obsessive-compulsive disorder (OCD). We sought to
      characterize predictors and course of response to IRT. METHODS: Admission,
      monthly, and discharge data were collected on individuals receiving IRT. We
      examined the association between baseline characteristics and percent change in
      OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)
      using linear regression. We compared baseline characteristics of IRT responders
      (>=35% reduction in Y-BOCS) versus non-responders, and of patients who did versus
      those who did not achieve wellness (Y-BOCS <= 12) using non-parametric tests. To
      examine the course of OCD severity over time, we used linear mixed-effects models
      with randomly varying intercepts and slopes. RESULTS: We evaluated 281
      individuals admitted to an IRT program. Greater baseline Y-BOCS scores were
      associated with a significantly greater percent reduction in Y-BOCS scores (beta
      = -1.49 ([95% confidence interval: -2.06 to -0.93]; P < .001)). IRT responders
      showed significantly greater baseline Y-BOCS scores than non-responders (mean
      (SD) 28 (5.2) vs. 25.6 (5.8); P = .003) and lower past-year alcohol use scores
      than non-responders (1.4 (1.9) vs. 2.1 (2.2); P = .01). Participants who achieved
      wellness displayed lower hoarding factor scores than those who did not (5 (4.6)
      vs. 9.53 (6.3); P = .03). OCD symptoms declined rapidly over the first month but
      more slowly over the remaining two months. CONCLUSIONS: Higher baseline OCD
      severity, lower past-year alcohol use, and fewer hoarding symptoms predicted
      better response to IRT. IRT yielded an initial rapid reduction in OCD symptoms,
      followed by a slower decline after the first month.

PMID- 24909789
TI  - Intracardiac leiomyomatosis: clinical findings and detailed echocardiographic
      features--a Chinese institutional experience.
AB  - BACKGROUND: Intravenous leiomyomatosis is a rare, benign, smooth muscle tumor
      originating in the uterus that may extend through the inferior vena cava into the
      heart. Intracardiac leiomyomatosis (ICL), present in 10% of patients with
      intravenous leiomyomatosis, may cause right heart failure, tricuspid valve
      obstruction, and pulmonary embolism. The imaging characteristics of ICL continue
      to be reported. The purposes of this study were to characterize the
      echocardiographic features of ICL and to correlate the clinical findings.
      METHODS: Between 1999 and 2012, 12 female patients with suspected ICL underwent
      cardiac surgery and histologic confirmation of the tumor. The clinical data,
      echocardiographic findings, and histologic results were retrospectively reviewed.
      RESULTS: The ages of the patients with ICL ranged from 40 to 59 years. Ten
      patients (83%) had undergone myomectomy or hysterectomy, one patient had a
      uterine fibroid, and one patient had endometriosis. Seven patients (58%) reported
      dyspnea and/or palpitations, and one patient had syncope; four patients were
      asymptomatic. Echocardiographic findings included six patients with homogenous
      right atrial masses, four patients with myxoma-like right atrial masses, and two
      patients with serpentine, convoluted right atrial masses. In nine patients, the
      right atrial masses were noted to cross the tricuspid valve. All masses extended
      from the inferior vena cava. No masses appeared to adhere to the right atrium,
      right ventricular or pulmonary arterial walls, or tricuspid valve. Tricuspid
      regurgitation was noted in all patients. No pulmonary emboli were present.
      CONCLUSIONS: The echocardiographic features of the ICL tumors varied. Tricuspid
      regurgitation and tumors emerging from the inferior vena cava were seen in all
      patients. Cardiac symptoms, including dyspnea, palpitations, and syncope,
      occurred in 67% of patients; the remaining 33% were asymptomatic.

PMID- 24909790
TI  - Proximal flow convergence method by three-dimensional color Doppler
      echocardiography for mitral valve area assessment in rheumatic mitral stenosis.
AB  - BACKGROUND: The two-dimensional (2D) proximal isovelocity surface area (PISA)
      method has important technical limitations for mitral valve orifice area (MVA)
      assessment in mitral stenosis (MS), mainly the geometric assumptions of PISA
      shape and the requirement of an angle correction factor. Single-beat real-time
      three-dimensional (3D) color Doppler imaging allows the direct measurement of
      PISA without geometric assumptions or the requirement of an angle correction
      factor. The aim of this study was to validate this method in patients with
      rheumatic MS. METHODS: Sixty-three consecutive patients with rheumatic MS were
      included. MVA was assessed using the transthoracic 2D and 3D PISA methods.
      Planimetry of MVA (2D and 3D) and the pressure half-time method were used as
      reference methods. RESULTS: The 3D PISA method had better correlations with the
      reference methods (with 2D planimetry, r = 0.85, P < .001; with 3D planimetry, r
      = 0.89, P < .001; and with pressure half-time, r = 0.85, P < .001) than the
      conventional 2D PISA method (with 2D planimetry, r = 0.63, P < .001; with 3D
      planimetry, r = 0.66, P < .001; and with pressure half-time, r = 0.68, P < .001).
      In addition, a consistent significant underestimation of MVA using the
      conventional 2D PISA method was observed. A high percentage (30%) of patients
      with nonsevere MS by 3D planimetry were misclassified by the 2D PISA method as
      having severe MS (effective regurgitant orifice area < 1 cm(2)). In contrast, the
      3D PISA method had 94% agreement with 3D planimetry. Good intra- and
      interobserver agreement for 3D PISA measurements were observed, with intraclass
      correlation coefficients of 0.95 and 0.90, respectively. CONCLUSIONS: MVA
      assessment using PISA by single-beat real-time 3D color Doppler echocardiography
      is feasible in the clinical setting and more accurate than the conventional 2D
      PISA method.

PMID- 24909791
TI  - Nitric oxide-mediated immunosuppressive effect of human amniotic membrane-derived
      mesenchymal stem cells on the viability and migration of microglia.
AB  - Human amniotic membrane-derived mesenchymal stem cells (AMSCs) are considered a
      novel and promising source of stem cells for cell replacement-based therapy.
      Current research is mostly limited to investigating the cellular differentiation
      potential of AMSCs, while few have focused on their immunosuppressive properties.
      This study is aimed at exploring and evaluating the immunosuppressive effect of
      human AMSCs on the viability and migratory properties of microglia. We found,
      from results of cell viability assays, that AMSCs can reduce the activity of
      inflammatory cells by secreting nitric oxide (NO). Also, based on results from
      wound healing and transwell migration assays, we show that AMSCs can inhibit the
      migration of human microglia as well as the mouse microglial cell line BV2,
      suggesting that they have the ability to inhibit the recruitment of certain
      immune cells to injury sites. Furthermore, we found that NO contributes
      significantly to this inhibitory effect. Our study provides evidence that human
      AMSCs can have detrimental effects on the viability and migration of microglia,
      through secretion of NO. This mechanism may contribute to anti-inflammatory
      processes in the central nervous system. 

PMID- 24909793
TI  - Computational modeling of 137Cs contaminant transfer associated with sediment
      transport in Abukuma River.
AB  - A numerical model capable of simulating the transfer of (137)Cs in rivers
      associated with transport of fine sediment is presented. The accident at
      Fukushima Dai-ichi Nuclear Power Plant (FDNPP) released radionuclides into the
      atmosphere, and after fallout several radionuclides in them, such as radiocesium
      ((134)Cs, (137)Cs) and radioiodine ((131)I) were adsorbed on surface soil
      particles around FDNPP and transported by surface water. To understand the
      transport and deposition of the radioactive contaminant along with surface soil
      particles and its flux to the ocean, we modeled the transport of the (137)Cs
      contaminant by computing the water flow and the associated washload and suspended
      load transport. We have developed a two-dimensional model to simulate the plane
      flow structure, sediment transport and associated (137)Cs contaminant transport
      in rivers by combining a shallow water flow model and an advection-diffusion
      equation for the transport of sediment. The proposed model has been applied to
      the lower reach of Abukuma River, which is the main river in the highly
      contaminated area around FDNPP. The numerical results indicate that most (137)Cs
      supplied from the upstream river reach with washload would directly reach to
      Pacific Ocean. In contrast, washload-oriented (137)Cs supplied from the upstream
      river basin has a limited role in the radioactive contamination in the river. The
      results also suggest that the proposed framework of computational model can be a
      potential tool for understanding the sediment-oriented (137)Cs behavior in
      rivers.

PMID- 24909795
TI  - Aggregatibacter actinomycetemcomitans infection mimicking lung cancer: a case
      report.
AB  - Pulmonary infections can mimic a pulmonary neoplasm. Multiple organisms,
      including bacteria, viruses, and fungi, can present with similar clinical,
      radiographic, and surgical findings as neoplastic processes. Because treatment
      and the prognosis are completely different, an accurate diagnosis is crucial, and
      lung biopsy is usually required. Aggregatibacter actinomycetemcomitans is part of
      the normal oral flora and is a rare cause of invasive infection due to
      hematogenous dissemination or aspiration, particularly infective endocarditis. We
      present a case of A. actinomycetemcomitans and Actinomyces co-infection that
      presented as a mediastinal mass, with surgical findings similar to lung
      malignancy but with biopsy and culture showing an infectious origin. After
      antibiotic treatment, follow-up images showed resolution of the mass.

PMID- 24909792
TI  - Involvement of the right hemisphere in reading comprehension: a DTI study.
AB  - The Simple View of reading emphasizes the critical role of two factors in normal
      reading skills: word recognition and reading comprehension. The current study
      aims to identify the anatomical support for aspects of reading performance that
      fall within these two components. Fractional anisotropy (FA) values were obtained
      from diffusion tensor images in twenty-one typical adolescents and young adults
      using the tract based spatial statistics (TBSS) method. We focused on the arcuate
      fasciculus (AF) and inferior longitudinal fasciculus (ILF) as fiber tracts that
      connect regions already implicated in the distributed cortical network for
      reading. Our results demonstrate dissociation between word-level and narrative
      level reading skills: the FA values for both left and right ILF were correlated
      with measures of word reading, while only the left ILF correlated with reading
      comprehension scores. FA in the AF, however, correlated only with reading
      comprehension scores, bilaterally. Correlations with the right AF were
      particularly robust, emphasizing the contribution of the right hemisphere,
      especially the frontal lobe, to reading comprehension performance on the
      particular passage comprehension test used in this study. The anatomical
      dissociation between these reading skills is supported by the Simple View theory
      and may shed light on why these two skills dissociate in those with reading
      disorders. 

PMID- 24909796
TI  - Phospholipase D is a central regulator of collagen I-induced cytoskeletal
      rearrangement and podosome formation in megakaryocytes.
AB  - BACKGROUND: Blood platelets are small anucleated cell fragments generated from
      bone marrow megakaryocytes (MKs) by a cytoskeleton-driven process. Thereby,
      mature MKs form long cytoplasmic protrusions (pro-platelets), which extend into
      the sinusoids within the bone marrow and finally release platelets. Podosomes are
      F-actin rich matrix contacts that have been suggested to play an important role
      in cell migration, but also in pro-platelet formation by MKs. Phospholipase D
      (PLD) has been proposed to contribute to the regulation of actin dynamics through
      the local generation of phosphatidic acid but its role in platelet formation is
      unknown. OBJECTIVE: We sought to investigate the significance of PLD in MK
      podosome formation and thrombocytopoiesis. METHODS: Podosome formation, spreading
      and ultra-structure of PLD single- and double-deficient MKs were analyzed using
      confocal and transmission electron microscopy. RESULTS: Phospholipase D-deficient
      MKs displayed a highly altered ultra-structure in vivo and abnormal actin
      rearrangement, with almost abolished formation of podosomes upon spreading on
      collagen I in vitro. However, MK endomitosis and platelet production were not
      altered by PLD deficiency. CONCLUSION: Together, our findings point to a specific
      function of PLD in actin dynamics as well as podosome formation and size
      determination in MKs on a collagen I matrix. The normal platelet number in PLD
      deficient mice, however, suggests the existence of compensatory mechanisms in
      vivo that overcome the defective podosome formation observed in vitro.

PMID- 24909797
TI  - Confirmatory factor analysis of the Oral Health Impact Profile.
AB  - Previous exploratory analyses suggest that the Oral Health Impact Profile (OHIP)
      consists of four correlated dimensions and that individual differences in OHIP
      total scores reflect an underlying higher-order factor. The aim of this report is
      to corroborate these findings in the Dimensions of Oral Health-Related Quality of
      Life (DOQ) Project, an international study of general population subjects and
      prosthodontic patients. Using the project's Validation Sample (n = 5022), we
      conducted confirmatory factor analyses in a sample of 4993 subjects with
      sufficiently complete data. In particular, we compared the psychometric
      performance of three models: a unidimensional model, a four-factor model and a
      bifactor model that included one general factor and four group factors. Using
      model-fit criteria and factor interpretability as guides, the four-factor model
      was deemed best in terms of strong item loadings, model fit (RMSEA = 0.05, CFI =
      0.99) and interpretability. These results corroborate our previous findings that
      four highly correlated factors - which we have named Oral Function, Oro-facial
      Pain, Oro-facial Appearance and Psychosocial Impact - can be reliably extracted
      from the OHIP item pool. However, the good fit of the unidimensional model and
      the high interfactor correlations in the four-factor solution suggest that OHRQoL
      can also be sufficiently described with one score.

PMID- 24909798
TI  - Comparison of radiography and computed tomography for determining tracheal
      diameter and length in dogs.
AB  - OBJECTIVE: To compare radiographic and computed tomography (CT) measurements of
      tracheal size as would be made for the purpose of tracheal stent size selection.
      STUDY DESIGN: Cross-over. ANIMALS: Dogs (n = 15). METHODS: Canine cadavers
      without evidence of tracheal or respiratory disease were used for CT and digital
      radiography of the neck and thorax. Three observers each made 3 independent
      measurements at each of 5 tracheal locations, and also measured tracheal length,
      on each radiograph and for each CT scan on each cadaver. RESULTS: CT tracheal
      measurements were on average 1.03 mm larger (P < .01) compared with radiographic
      measurements for all 3 observers. CONCLUSIONS: Radiographic measurements of the
      canine trachea consistently underestimate tracheal size, and CT measurements are
      preferable for selecting tracheal stent size.

PMID- 24909799
TI  - Effect of beta-cryptoxanthin plus phytosterols on cardiovascular risk and bone
      turnover markers in post-menopausal women: a randomized crossover trial.
AB  - BACKGROUND AND AIM: Post-menopausal women are at higher risk of cardiovascular
      disease and bone demineralization. Phytosterols (PS) may be used for
      hypercholesterolemia in some groups and beta-cryptoxanthin (beta-Cx) displays a
      unique anabolic effect on bone. Our aim was to assess the changes in
      cardiovascular and bone turnover markers from the oral intake of beta-Cx and PS
      in post-menopausal women. METHODS AND RESULTS: A randomized, double-blind,
      crossover study with beta-Cx (0.75 mg/day) and PS (1.5 g/day), single and
      combined, was performed in 38 postmenopausal women. Diet was supplemented with 1
      * 250 mL milk-based fruit drink/day for 4 weeks with a wash-out period of 4-weeks
      in between. Serum beta-Cx and PS were determined by UPLC and CG-FID respectively.
      Outcome variables included markers of bone turnover and cardiovascular risk.
      Biological effect was assessed by paired t test and generalized estimating
      equations analysis that included the previous treatment, the order of
      intervention and the interactions. The intake of beverages containing beta-Cx and
      PS brought about a significant increase in serum levels of beta-Cx, beta
      sitosterol and campesterol. Intervention caused changes in almost all the markers
      while the order, previous treatment and the interaction did not reach statistical
      significance. Only the intake of the beverage containing beta-Cx plus PS brought
      about significant decreases in total cholesterol, c-HDL, c-LDL and bone turnover
      markers. CONCLUSIONS: beta-Cx improves the cholesterol-lowering effect of PS when
      supplied simultaneously and this combination may also be beneficial in reducing
      risk of osteoporosis. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov number
      NCT01074723.

PMID- 24909800
TI  - Treatment of refractory Aspergillus otomycosis with voriconazole: case series and
      review.
AB  - BACKGROUND: Voriconazole is a broad-spectrum azole exhibiting strong anti
      Aspergillus activity and good long-term tolerance. However, the evidence for
      voriconazole efficacy against refractory Aspergillus otomycosis is weak. METHOD:
      We reviewed the medical records of patients with Aspergillus otomycosis treated
      with voriconazole from January 2008 to June 2012 in a Taiwanese regional
      hospital. Demographic data and information regarding underlying diseases,
      clinical features, treatment and outcome were assessed. RESULTS: In total, 14
      cases of Aspergillus otomycosis were treated with voriconazole, including 5
      patients with Aspergillus invasive otitis externa. All patients had failed to
      respond to local treatment, antibiotics or topical agents. One case was lost to
      follow up. The symptoms of two patients recurred after voriconazole treatment:
      one patient received a second 12-week course of voriconazole and was cured; and
      symptoms of the other patient recurred after a second 12-week course of
      voriconazole, leading to surgical debridement. The remaining 11 patients were
      cured by voriconazole treatment without extensive surgical debridement.
      CONCLUSION: This study demonstrates that voriconazole can be a very effective and
      convenient therapeutic option for the management of refractory Aspergillus
      otomycosis.

PMID- 24909801
TI  - Self-Reported Versus Accelerometer-Measured Physical Activity and Biomarkers
      Among NHANES Youth.
AB  - BACKGROUND: Discrepancies in self-report and accelerometer-measured moderate-to
      vigorous physical activity (MVPA) may influence relationships with obesity
      related biomarkers in youth. METHODS: Data came from 2003-2006 National Health
      and Nutrition Examination Surveys (NHANES) for 2174 youth ages 12 to 19.
      Biomarkers were: body mass index (BMI, kg/m2), BMI percentile, height and waist
      circumference (WC, cm), triceps and subscapular skinfolds (mm), systolic &
      diastolic blood pressure (BP, mmHg), high-density lipoprotein (HDL, mg/dL), total
      cholesterol (mg/dL), triglycerides (mg/dL), insulin (MUU/ml), C-reactive protein
      (mg/dL), and glycohemoglobin (%). In separate sex-stratified models, each
      biomarker was regressed on accelerometer variables [mean MVPA (min/day),
      nonsedentary counts, and MVPA bouts (mean min/day)] and self-reported MVPA.
      Covariates were age, race/ethnicity, SES, physical limitations, and asthma.
      RESULTS: In boys, correlations between self-report and accelerometer MVPA were
      stronger (boys: r = 0.14-0.21; girls: r = 0.07-0.11; P < .010) and there were
      significant associations with BMI, WC, triceps skinfold, and SBP and
      accelerometer MVPA (P < .01). In girls, there were no significant associations
      between biomarkers and any measures of physical activity. CONCLUSIONS: Physical
      activity measures should be selected based on the outcome of interest and study
      population; however, associations between PA and these biomarkers appear to be
      weak regardless of the measure used.

PMID- 24909802
TI  - Cyclodextrin and phospholipid complexation in solubility and dissolution
      enhancement: a critical and meta-analysis.
AB  - INTRODUCTION: Poor solubility and dissolution of drugs are the major challenges
      in drug formulation and delivery. In order to improve the solubility and
      dissolution profile of drugs, various methods have been investigated so far. The
      cyclodextrin (CD) complexation and phospholipid (PL) complexation are among the
      exhaustively investigated methods employed for more precise improvement of the
      solubility and dissolution of poorly water-soluble drugs. AREAS COVERED: The
      article discusses the CD and PL complexation techniques of solubility and
      dissolution enhancement. Various studies reporting the CD and PL complexation as
      the potential approaches to improve the dissolution, absorption and the
      bioavailability of the drugs have been discussed. The article critically reviews
      the physicochemical properties of CDs and PLs, eligibility of drugs for both the
      complexation, thermodynamics of complexation, methods of preparation,
      characterization, advantages, limitation and the meta-analysis of some studies
      for both the techniques. EXPERT OPINION: The CD and PL complexation techniques
      are very useful in improving solubility and dissolution (and hence the
      bioavailability) of biopharmaceutical classification system Class II and Class IV
      drugs. The selection of a particular kind of complexation can be made on the
      basis of eligibility criteria (of drugs) for the individual techniques, cost,
      stability and effectiveness of the complexes.

PMID- 24909803
TI  - Anaphylaxis: guidelines from the European Academy of Allergy and Clinical
      Immunology.
AB  - Anaphylaxis is a clinical emergency, and all healthcare professionals should be
      familiar with its recognition and acute and ongoing management. These guidelines
      have been prepared by the European Academy of Allergy and Clinical Immunology
      (EAACI) Taskforce on Anaphylaxis. They aim to provide evidence-based
      recommendations for the recognition, risk factor assessment, and the management
      of patients who are at risk of, are experiencing, or have experienced
      anaphylaxis. While the primary audience is allergists, these guidelines are also
      relevant to all other healthcare professionals. The development of these
      guidelines has been underpinned by two systematic reviews of the literature, both
      on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a
      potentially life-threatening condition whose clinical diagnosis is based on
      recognition of a constellation of presenting features. First-line treatment for
      anaphylaxis is intramuscular adrenaline. Useful second-line interventions may
      include removing the trigger where possible, calling for help, correct
      positioning of the patient, high-flow oxygen, intravenous fluids, inhaled short
      acting bronchodilators, and nebulized adrenaline. Discharge arrangements should
      involve an assessment of the risk of further reactions, a management plan with an
      anaphylaxis emergency action plan, and, where appropriate, prescribing an
      adrenaline auto-injector. If an adrenaline auto-injector is prescribed, education
      on when and how to use the device should be provided. Specialist follow-up is
      essential to investigate possible triggers, to perform a comprehensive risk
      assessment, and to prevent future episodes by developing personalized risk
      reduction strategies including, where possible, commencing allergen
      immunotherapy. Training for the patient and all caregivers is essential. There
      are still many gaps in the evidence base for anaphylaxis. 

PMID- 24909804
TI  - Digital planning for foot and ankle deformity correction: Evans osteotomy.
AB  - Preoperative planning is commonly performed for many foot and ankle procedures.
      The purpose of the present study was to prospectively determine the preoperative
      digital planning accuracy of predicting the calcaneal graft size used during the
      "Evans" calcaneal osteotomy. Preoperative digital deformity correction planning,
      using a standard planning method (TraumaCad((r)) software), was performed on 10
      feet scheduled to undergo an Evans procedure. Of the 10 patients, 6 were female
      and 4 were male, with an average age of 43 +/- 22 years. Digital planning was
      used to predict the Evans graft size. The surgeon was unaware of the predicted
      graft size, which was then compared with the actual graft size inserted during
      the procedure. In addition, the pre- and postoperative radiographic angles were
      recorded and compared (anteroposterior view, talo-first metatarsal angle,
      calcaneocuboid abduction; lateral view, calcaneal inclination angle; and axial
      view, tibial-calcaneal angle). The average preoperative talo-first metatarsal
      angle, calcaneocuboid angle, calcaneal inclination angle, and tibial-calcaneal
      angle measured 21 degrees  +/- 9.6 degrees , 28.3 degrees  +/- 9.0 degrees , 13.8
      degrees  +/- 5.7 degrees , and 15.3 degrees  +/- 8.2 degrees , respectively. The
      preoperative tibial-calcaneal position was 2.8 +/- 1.2 mm. The radiographic
      weightbearing angles measured at an average follow-up of 7.4 (range 6 to 12)
      months improved to 6.3 degrees  +/- 7.4 degrees  (p = .0015), 12.3 degrees  +/-
      6.1 degrees  (p < .001), 21.3 degrees  +/- 7.7 degrees  (p = .0122), and 2.2
      degrees  +/- 3.6 degrees  (p = .0019) for the talo-first metatarsal,
      calcaneocuboid abduction, calcaneal inclination, and tibial-calcaneal angles,
      respectively. The final tibial-calcaneal position measured 1.4 +/- 0.7 mm (p <
      .001). The preoperative Evans graft measurement (11.8 +/- 2.6 mm) compared with
      the actual graft (12.2 +/- 1.3 mm) placed was within 0.4 +/- 1.8 mm (p = .51).
      Preoperative digital planning for Evans calcaneal osteotomy has been shown to be
      a valuable tool for predicting the surgical graft size for accurate pedal
      realignment.

PMID- 24909805
TI  - Association of plasma fibrinogen and plasminogen with prognosis of inoperable
      chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: It is unclear whether abnormalities of coagulation or fibrinolysis
      are associated with disease progression of chronic thromboembolic pulmonary
      hypertension (CTEPH). The aim of this study was to investigate the association of
      these factors with the severity and prognosis of CTEPH. METHODS AND RESULTS:
      Between 1986 and 2011, plasma fibrinogen and plasminogen were measured in 89 of
      106 consecutive patients with inoperable CTEPH (17 men; mean age, 55.9+/-14.1
      years old; mean pulmonary arterial pressure, 44.0+/-12.4 mmHg) and the
      association of level with severity and prognosis were also examined. Seventeen
      patients had high fibrinogen and low plasminogen (medians, >=291 mg/dl and <101%,
      respectively). These patients had significantly lower cardiac index (2.26+/-0.68
      vs. 2.70+/-0.57 L.min(-1).m(-2), P=0.007), higher pulmonary vascular resistance
      (PVR; 13.29+/-7.54 vs. 9.15+/-4.14 Wood units, P=0.003), and poor survival (5
      year survival, 35.3% vs. 88.0%, P<0.001) compared to the other 72 patients.
      Additional analysis showed significantly poor survival in these patients compared
      with the other patients who did not have modern therapy. On multivariate analysis
      plasma fibrinogen, plasminogen and PVR were independent predictors of survival in
      medically treated patients. CONCLUSIONS: High plasma fibrinogen and low
      plasminogen are associated with poor survival in CTEPH patients without modern
      therapy.

PMID- 24909806
TI  - Acute retrograde ascending aortic dissection during thoracic endovascular aortic
      repair in a rare triple-barreled aortic dissection.

PMID- 24909807
TI  - Role of endothelial dysfunction in thrombus formation in the left atrium
      protective role of nitric oxide synthesis in the surface of atrium.

PMID- 24909808
TI  - Therapeutic modulation of gut microbiota: current clinical applications and
      future perspectives.
AB  - Human beings and gut microbiota are in a symbiotic relationship, and the
      hypothesis of a "super organism" composed of the human organism and microbes has
      been recently proposed. The gut microbiota fulfills important metabolic and
      immunological tasks, and the impairment of its composition might alter
      homeostasis and lead to the development of microbiota-related diseases. The most
      common illnesses associated with alterations of the gut microbiota include
      inflammatory bowel disease, gastroenteric infections, irritable bowel syndrome
      and other gastrointestinal functional diseases, colorectal cancer, metabolic
      syndrome and obesity, liver diseases, allergic diseases, and neurological
      diseases such as autism. In theory, every disease associated with the impairment
      of intestinal microflora might benefit from the therapeutic modulation of the gut
      microbiota. A number of attempts to manipulate the microbiota have not produced
      identical results for every disease. Although antibiotics and probiotics have
      been available for a long time, the so-called fecal microbiota transplantation,
      which is a very old remedy, was only recently re-evaluated as a promising
      therapeutic approach for microbiota impairment. A comprehensive understanding of
      the gut microbiota composition, in states of both health and various diseases, is
      needed for the development of future approaches for microbiota modulation and for
      developing targeted therapies. In this review, we describe the role of the
      microbiota in several diseases and the related treatment options that are
      currently available. 

PMID- 24909809
TI  - Effect of TNF-alpha inhibitor treatment on bone mineral density in patients with
      ankylosing spondylitis: a systematic review and meta-analysis.
AB  - OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory disease
      associated with an increased risk of osteoporosis and fractures. TNF inhibitors
      have been used to treat AS, but their effect on bone is unclear. Thus, we
      conducted a meta-analysis to study the effect of TNF inhibitors on spine and hip
      BMD in patients with AS. METHODS: Two authors independently searched MEDLINE and
      PubMed for longitudinal studies that had assessed the effect of TNF inhibitors on
      BMD in patients with AS. Studies with a minimum follow-up period of 1 year were
      included. RESULTS: Seven longitudinal studies and one randomized control trial
      were included, with a total of 568 AS patients (mean age range of 36-48 years and
      disease duration of 9-17 years). Lumbar spine BMD increased by 5.1% (95% CI: 4.0
      6.1%, p = 0.00000) after 1 year of treatment with TNF inhibitors and by 8.6% (95%
      CI: 6.8-10.3%, p < 0.00001) after 2 years. Significant improvements in total hip
      BMD were also noted after 1 [1.8% (1.0-2.5%)] and 2 years [2.5% (1.9-3.0%)].
      Compared to baseline, femoral neck BMD remained stable after 1 year [0.7% (-0.8%
      to 2.2%), p = 0.34]. No significant heterogeneity was noted amongst the included
      studies. CONCLUSIONS: TNF inhibitors can increase lumbar spine and total hip BMD
      and maintain femoral neck BMD for up to 2 years in patients with AS. More
      research is needed to assess the effect of TNF inhibitors on bone quality and
      fracture risk.

PMID- 24909810
TI  - Interaction of decidual CD56+ NK with trophoblast cells during normal pregnancy
      and recurrent spontaneous abortion at early term of gestation.
AB  - The immunological paradox of pregnancy, when maternal immune system recognizes
      but does not reject the semiallogenic foetus, is not yet fully understood. The
      aim of this work was to detail the mechanisms of the interaction of decidual
      CD56+ NK, infiltrating the maternal part of placenta, and trophoblast cells of
      foetal origin. Samples of the endometrial tissue from 13 healthy non-pregnant
      women, 37 placentas, obtained after medical abortion of viable pregnancy at 7-10
      weeks of gestation, and 26 samples of placentas from first-trimester recurrent
      spontaneous abortion (RSA) were used as the material for investigation. Phenotype
      of NK was assessed by flow cytometry. The influence of trophoblast cells upon
      IFNgamma and GrB mRNAs expression by dNK was investigated by RT-PCR. The
      influence of dNK upon trophoblast cells migration and invasion was studied using
      collagen and Matrigel systems. In RSA group comparing to the normal pregnancy,
      the decrease of dNK with inhibitory receptors (NKG2A) and elevation of activated
      dNK were seen. In normal pregnancy, but not in RSA, trophoblast cells increased
      the expression of IFNgamma and GrB mRNAs by CD56+ dNK. Both in normal and RSA
      pregnancy, dNK inhibited the migration and invasion of trophoblast cells.
      Initially, low invasive and migration capacities of trophoblast cells were seen
      during RSA. Thus, unbalanced activation of dNK can lead to the impairment of dNK
      and trophoblast cells interaction during RSA. 

PMID- 24909811
TI  - Glucagon-like peptide-1 analog-mediated protection against cholesterol-induced
      apoptosis via mammalian target of rapamycin activation in pancreatic betaTC-6
      cells -1mTORbetaTC-6.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic
      beta-cells against glucolipotoxicity via activation of the Akt pathway. The
      present study investigated the protective effects of the GLP-1 analog liraglutide
      against cholesterol-induced lipotoxicity and the mechanisms involved. METHODS:
      The mouse betaTC-6 pancreatic beta-cell line was preincubated for 30 min with 10
      nmol/L liraglutide alone or in combination with the mammalian target of rapamycin
      (mTOR) inhibitor rapamycin (1 MUmol/L) before being exposed to 5 mmol/L
      cholesterol for 6 h. 4',6'-Diamidino-2-phenylindole (DAPI) staining and Western
      blot analyses were used to assess the effects of liraglutide on cholesterol
      induced apoptosis and the phosphorylation of Akt and mTOR. RESULTS: Cholesterol
      significantly promoted cell apoptosis and attenuated the phosphorylation of Akt
      and mTOR, effects that were significantly reversed by liraglutide. Furthermore,
      rapamycin pretreatment alone significantly increased cholesterol-induced
      apoptosis compared with cholesterol-treated cells without any other pretreatment.
      CONCLUSIONS: The data indicate that mTOR signaling is an essential mediator in
      the protection of pancreatic beta-cells against cholesterol-induced apoptosis by
      a GLP-1 analog.

PMID- 24909812
TI  - The influence of non-HLA antibodies directed against angiotensin II type 1
      receptor (AT1R) on early renal transplant outcomes.
AB  - Non-HLA antibodies (Abs) targeting vascular receptors are thought to have an
      impact on renal transplant injury. Anti-angiotensin II type 1-receptor-activating
      antibodies (anti-AT1R) have been mentioned to stimulate a severe vascular
      rejection, but the pretransplant screening has not been introduced yet. The aim
      of our study was to assess the incidence and importance of anti-AT1R antibodies
      and their influence on renal transplant in the 1st year of observation. We
      prospectively evaluated the presence of anti-AT1R antibodies in 117 consecutive
      renal transplant recipients in pre- and post-transplant screening. Anti-AT1R
      antibodies were observed in 27/117 (23%) of the analyzed recipients already
      before transplantation. The function of renal transplant was considerably worse
      in anti-AT1R(+) group. The patients with anti-AT1R Abs >9 U/ml lost their graft
      more often. Biopsy-proven AR was described in 4/27 (15%) pts in the anti-AT1R(+)
      group and 13/90 (14.4%) in the anti-AT1R(-) group, but more severe cases of Banff
      IIB or antibody-mediated rejection (AMR) were more often observed in anti-AT1R
      (+) 4/27 (15%) vs. 1/90 (1.1%) in anti-AT1R(+) (P = 0.009). Patients with anti
      AT1R Abs level >9 U/ml run a higher risk of graft failure independently of
      classical immunological risk factors. The recipients with anti-AT1R Abs developed
      more severe acute rejections described as IIB or AMR in Banff classification.
      More recipients among the anti-AT1R-positive ones lost the graft. Our study
      suggests monitoring of anti-AT1R Abs before renal transplantation for assessment
      of immunologic risk profiles and the identification of patients highly
      susceptible to immunologic events, graft failure, and graft loss. 

PMID- 24909813
TI  - Confined mobility in biomembranes modeled by early stage Brownian motion.
AB  - An equation of motion, derived from the fractal analysis of the Brownian particle
      trajectory, makes it possible to calculate the time dependence of the mean square
      displacement for early times, before the Einstein formula becomes valid. The
      diffusion coefficient increases with the distance travelled which can be
      restricted by the geometrical conditions. The corresponding diffusion coefficient
      cannot increase further to achieve a value characteristic for unrestricted
      environment. Explicit formula is derived for confined diffusivity related to the
      unrestricted one as dependent on the maximum particle mean square displacement
      possible normalized by the square of its mean free path. The model describes the
      lipid and protein diffusion in tubular membranes with different radii, originally
      fitted by the modified Saffman-Delbruck equation, and the lateral mobility of
      synthetic model peptides for which the diffusion coefficient is inversely
      proportional to the radius of the diffusing object and to the thickness of the
      membrane. 

PMID- 24909814
TI  - Preparing for family caregiving in specialized palliative home care: an ongoing
      process.
AB  - OBJECTIVE: Family caregivers have been given increasing importance in palliative
      home care and face a great responsibility as caregivers for patients suffering
      from incurable illness. Preparedness for caregiving has been found to moderate
      negative effects and promote well-being in family caregivers. The aim of our
      study was to explore family caregivers' own experiences of preparing for
      caregiving in specialized palliative home care. METHOD: An interpretive
      descriptive design was chosen. A strategic sampling method was applied with a
      focus on participants who rated their preparedness as high and low using a
      structured instrument. Qualitative interviews were completed with 12 family
      caregivers. They were analyzed using a constant-comparative technique. RESULTS:
      Family caregivers described their experience of preparing for caregiving as an
      ongoing process, rather than something done in advance. The process was
      illustrated through three subprocesses: "awaring" (realizing the seriousness of
      the situation), "adjusting" (managing a challenging situation), and
      "anticipating" (planning for the inevitable loss). SIGNIFICANCE OF RESULTS:
      Knowledge about the process of preparedness for caregiving and its subprocesses
      could be valuable to healthcare professionals, given the positive effects shown
      by preparedness in this context. Being able to recognize the different
      subprocesses of preparedness for caregiving could provide healthcare
      professionals with opportunities to support family caregivers in managing them.
      Preparedness for caregiving should be seen as a process to be supported and
      promoted continuously in palliative home care, not just at enrollment.

PMID- 24909815
TI  - Molecular dynamics study of the conformations of glycosidic linkages in sialic
      acid modified ganglioside GM3 analogues.
AB  - The objective of the present study is to model the analogues of
      monosialoganglioside (GM3) by making modifications in its sialic acid residue
      with different substitutions in aqueous environment and to determine their
      structural stability based upon computational molecular dynamics. Molecular
      mechanics and molecular dynamics investigation was carried out to study the
      conformational preferences of the analogues of GM3. Dynamic simulations were
      carried out on the analogues of GM3 varying in the substituents at C-1, C-4, C-5,
      C-8 and C-9 positions of their sialic acid or Neuraminic acid (NeuAc) residue.
      The analogues are soaked in a periodic box of TIP3P water as solvent and
      subjected to a 10 ns molecular dynamics (MD) simulation using AMBER ff03 and gaff
      force fields with 30 ps equilibration. The analogue of GM3 with 9-N-succNeuAc
      (analogue5, C9 substitution) was observed to have the lowest energy of -6112.5
      kcal/mol. Graphical analysis made on the MD trajectory reveals the direct and
      water mediated hydrogen bonds existing in these sialic acid analogues. The
      preferable conformations for glycosidic linkages of GM3 analogues found in
      different minimum energy regions in the conformational maps were identified. This
      study sheds light on the conformational preferences of GM3 analogues which may be
      essential for the design of GM3 analogues as inhibitors for different ganglioside
      specific pathogenic proteins such as bacterial toxins, influenza toxins and
      neuraminidases.

PMID- 24909816
TI  - TLR7 is a key regulator of innate immunity against Japanese encephalitis virus
      infection.
AB  - Toll-like receptor 7 (TLR7) known to recognize guanidine-rich ssRNA has been
      shown to mount vital host defense mechanism against many viruses including
      flaviviruses. Signal transduction through TLR7 has been shown to produce type-1
      interferon and proinflammatory mediators, thereby initiating essential innate
      immune response against ssRNA viruses in hosts. Systemic and brain specific TLR7
      knock-down mice (TLR7(KD)) were generated using vivo-morpholinos. These mice were
      then subcutaneously challenged with lethal dose of JEV (GP78 strain) and were
      subsequently analyzed for survival. Significant difference in susceptibility to
      JEV between wild-type and systemic TLR7(KD) mice was observed whereas, no
      difference in susceptibility to JEV infection was seen in brain-specific TLR7(KD)
      mice. Significant decreases in IFN-alpha and antiviral proteins were also
      observed in both TLR7(KD) mice along with increased viral loads in their brain.
      Owing to increased viral load, increases in levels of various proinflammatory
      cyto/chemokines, increased microglial activation and infiltration of peripheral
      immune cells in brain of TLR7(KD) mice were also observed. Immunocytochemistry
      and RNA co-immunoprecipitation performed with JEV-infected N2a or HT22 cells
      indicated endosomal localization and confirmed interaction between JEV ssRNA with
      TLR7. Treatment of mice with imiquimod, a TLR7 agonist, prior to JEV infection
      resulted in their increased survival. Overall, our results suggest that the TLR7
      response following JEV infection promotes type-1 interferon production and
      generation of antiviral state which might contribute to protective effect in
      systemic infection. 

PMID- 24909817
TI  - A Web platform for the interactive visualization and analysis of the 3D fractal
      dimension of MRI data.
AB  - This study presents a Web platform (http://3dfd.ujaen.es) for computing and
      analyzing the 3D fractal dimension (3DFD) from volumetric data in an efficient,
      visual and interactive way. The Web platform is specially designed for working
      with magnetic resonance images (MRIs) of the brain. The program estimates the
      3DFD by calculating the 3D box-counting of the entire volume of the brain, and
      also of its 3D skeleton. All of this is done in a graphical, fast and optimized
      way by using novel technologies like CUDA and WebGL. The usefulness of the Web
      platform presented is demonstrated by its application in a case study where an
      analysis and characterization of groups of 3D MR images is performed for three
      neurodegenerative diseases: Multiple Sclerosis, Intrauterine Growth Restriction
      and Alzheimer's disease. To the best of our knowledge, this is the first Web
      platform that allows the users to calculate, visualize, analyze and compare the
      3DFD from MRI images in the cloud. 

PMID- 24909818
TI  - Signaling related with biphasic effects of bisphenol A (BPA) on Sertoli cell
      proliferation: a comparative proteomic analysis.
AB  - BACKGROUND: Biphasic effects on cell proliferation of bisphenol A (BPA) can occur
      at lesser or greater exposures. Sertoli cells play a pivotal role in supporting
      proliferation and differentiation of germ cells. The mechanisms responsible for
      inverse effects of great and low concentrations of BPA on Sertoli cell
      proliferation need further study. METHODS: We utilized proteomic study to
      identify the protein expression changes of Sertoli TM4 cells treated with 10(-8)M
      and 10(-5)M BPA. The further mechanisms related to mitochondria, energy
      metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting
      analysis. RESULTS: Proteomic studies identified 36 proteins and two major
      clusters of proteins including energy metabolism and oxidative stress expressed
      with opposite changes in Sertoli cells treated with 10(-8)M and 10(-5)M BPA,
      respectively, for 24h. Exposure to 10(-5)M BPA resulted in greater oxidative
      stress and then inhibited cell proliferation, while ROS scavenger NAC effectively
      blocked these effects. Exposure to 10(-8)M BPA caused higher intercellular ATP,
      greater activities of mitochondria, and resulted in significant proliferation of
      TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these
      growth advantages. CONCLUSIONS: Our study demonstrated that micromolar BPA
      inhibits proliferation of Sertoli cells by elevating oxidative stress while
      nanomolar BPA stimulates proliferation by promoting energy metabolism. GENERAL
      SIGNIFICANCE: Micromolar BPA inhibits cell proliferation by elevating oxidative
      stress while nanomolar BPA stimulates cell proliferation by promoting energy
      metabolism.

PMID- 24909819
TI  - Normal values and symptom correlation of a simplified oatmeal-based gastric
      emptying study in the Chinese population.
AB  - BACKGROUND AND AIM: Instant oatmeal has been proposed as a good alternative to
      the standardized low-fat egg white test meal for gastric emptying studies. We aim
      to establish normal values of oatmeal-based gastric emptying scintigraphy and
      test its correlation with gastroparesis symptoms in the Chinese population.
      METHODS: This study prospectively enrolled 60 healthy volunteers, 30 functional
      dyspepsia and 30 diabetes patients with gastroparesis symptoms. All participants
      were evaluated using the Gastroparesis Cardinal Symptom Index. Each participant
      ingested instant oatmeal mixed with 1 mCi of (99m) Tc
      diethylenetriaminepentacetic acid, and serial imaging was immediately acquired
      for 3 h in the supine position using a left anterior oblique projection. Time
      activity curves were generated and quantitative parameters were determined.
      Normal values were established from healthy volunteers and further applied in the
      symptomatic patients. RESULTS: All participants finished the test meal and
      tolerated the procedure well. All gastric emptying parameters were not
      significantly affected by age or gender. Values above the 95th percentile of T1/2
      , gastric retention at 1, 2, and 3 h (85 min, 65%, 28%, and 8%, respectively)
      were indicative of delayed gastric emptying. Values below the 5th percentile of
      gastric retention at 0.5 and 1 h (40% and 15%, respectively) were indicative of
      rapid gastric emptying. The lower gastric retention limit at 0.5 and 1 h were 40%
      and 15%, respectively. Four (13.3%) diabetes and four (13.3%) functional
      dyspepsia patients had delayed emptying while three diabetes patients (10%) had
      rapid emptying. Gastric emptying parameters correlated best with vomiting (r =
      0.621) and nausea (r = 0.566) in diabetes patients. CONCLUSIONS: We established
      normal values of oatmeal-based gastric emptying scintigraphy and observed good
      correlation with cardinal gastroparesis symptoms in the Chinese population.

PMID- 24909820
TI  - Author reply: To PMID 23419803.

PMID- 24909821
TI  - A computer-based comparative quantitative analysis of surgical outcome of
      mandibular reconstructions with free fibula microvascular flaps.
AB  - The free fibula osteoseptocutaneous flap is the standard for reconstruction of
      extensive mandibular defects. The procedure must be precise to achieve the
      required functional and aesthetic results. The aim of the present study was to
      calculate retrospectively the exact differences in surgical outcome based on
      preoperative and postoperative Computed Tomography data sets. Ten patients with
      unilateral reconstructions of the mandible with a fibula based on conventional
      planning were analyzed quantitatively, applying mirroring techniques with direct
      comparison of the theoretically optimum with the actual reconstruction. The
      results showed that there is a significant discrepancy between what is actually
      achieved and the theoretical optimum. The result of the present retrospective
      analysis shows that there is room for further improvement of the outcome in
      complex mandible reconstruction cases. 

PMID- 24909822
TI  - Effects of mature adipocyte-derived dedifferentiated fat (DFAT) cells on
      generation and vascularisation of dermis-like tissue after artificial dermis
      grafting.
AB  - Although artificial dermis (AD) is effective for skin reconstruction, it requires
      two separate procedures, because the AD must be vascularised before skin grafts.
      To shorten the period of the dermis-like tissue generation before the secondary
      skin grafting must be beneficial. Dedifferentiated fat (DFAT) cells are isolated
      from mature adipose cell suspensions and have potential to differentiate into
      multiple cell types including endothelial cells. This study aimed to investigate
      effects of DFAT cells on dermal regeneration after AD grafts in rats. The effects
      of combination use of DFAT cells and basic fibroblast growth factor (bFGF) were
      also tested to mimic clinical situations. DFAT cells were isolated from SD rats.
      Full-thickness wounds were created on the back of rats followed by AD grafting.
      Five groups were established; Group I: control, Group II: treated with DFAT
      cells, Group III: treated with bFGF, Group IV: treated with both of DFAT cells
      and bFGF, and Group V: treated with Green fluorescent protein (GFP)-labelled DFAT
      cells and bFGF. Histological evaluation was serially performed. Group IV showed
      markedly promoted vascularisation of dermis-like tissue. In particular, capillary
      infiltration into the dermis was obtained within 2 days. Immunohistochemical
      examination revealed that the transplanted DFAT cells had differentiated into
      endothelial cells and participated in angiogenesis. Group IV also showed a marked
      increase in the thickness of the dermis like tissue. The present results suggest
      that the use of DFAT cells under bFGF treatment could be beneficial to shorten
      the period required for dermal regeneration and vascularisation and contribute to
      use AD more effectively and safely.

PMID- 24909823
TI  - Reaction to: Persson et al. Educational achievements in Pierre Robin sequence. J
      Plast Surg Hand Surg 2013;47(1):36-9.

PMID- 24909824
TI  - Does shining light on gold colloids influence aggregation?
AB  - In this article we revisit the much-studied behavior of self-assembled aggregates
      of gold colloidal particles. In the literature, the electrostatic interactions,
      van der Waals interactions, and the change in free energy due to ligand-ligand or
      ligand-solvent interactions are mainly considered to be the dominating factors in
      determining the characteristics of the gold aggregates. However, our light
      scattering and imaging experiments clearly indicate a distinct effect of light in
      the growth structure of the gold colloidal particles. We attribute this to the
      effect of a non-uniform distribution of the electric field in aggregated gold
      colloids under the influence of light. 

PMID- 24909825
TI  - Uptake of influenza vaccination and risk reduction behaviour for respiratory
      infections: a survey of optometrists in New Zealand.
AB  - BACKGROUND: The aim was to determine the uptake of seasonal influenza vaccination
      and risk reduction behaviours among a health professional group with close
      patient contact, namely, optometrists. This group can have close facial proximity
      to patients during eye examinations. METHODS: National telephone survey of
      optometrists in New Zealand. RESULTS: Seventy per cent of registered optometrists
      participated (n = 450 responses). Less than one-third (29.7 per cent, 95% CI:
      27.4 to 32.0) of optometrists reported having had the seasonal influenza
      vaccination in 2012. The major reason given for not being vaccinated was that the
      vaccination was considered unnecessary (47 per cent) followed by 'time
      constraints' (28 per cent). During their last respiratory illness, 82 per cent
      reported working with symptoms and only 16 per cent reported the use of a face
      mask. CONCLUSION: There is major scope for increasing uptake of influenza
      vaccination and other protective behaviour for such health professional groups,
      especially those characterised by relatively close patient contact. Possible
      options include educational campaigns and government-funded vaccinators visiting
      the workplaces of all health-care workers.

PMID- 24909826
TI  - Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2.
AB  - Cell migration is an integral part of re-epithelialization during skin wound
      healing, a complex process involving molecular controls that are still largely
      unknown. Here we identify a novel role for Tcf3, an essential transcription
      factor regulating embryonic and adult skin stem cell functions, as a key effector
      of epidermal wound repair. We show that Tcf3 is upregulated in skin wounds and
      that Tcf3 overexpression accelerates keratinocyte migration and skin wound
      healing. We also identify Stat3 as an upstream regulator of Tcf3. We show that
      the promigration effects of Tcf3 are non-cell autonomous and occur independently
      of its ability to interact with beta-catenin. Finally, we identify lipocalin-2 as
      the key secreted factor downstream of Tcf3 that promotes cell migration in vitro
      and wound healing in vivo. Our findings provide new insights into the molecular
      controls of wound-associated cell migration and identify potential therapeutic
      targets for the treatment of defective wound repair. 

PMID- 24909827
TI  - Early adiposity rebound is associated with metabolic risk in 7-year-old children.
AB  - BACKGROUND: Early adiposity rebound (AR <5 years) has been consistently
      associated with increased obesity risk, but its relationship with metabolic
      markers is less clear; in addition, the biologic mechanisms involved in these
      associations have not been established. OBJECTIVE: The objective of this study
      was to assess the association between timing of AR and metabolic status at age 7
      years, evaluating the potential role of adiposity, adipose functionality and
      skeletal maturation in this association. DESIGN: We estimated the age of AR from
      the body mass index (BMI) trajectories from 0 to 7 years in 910 children from the
      Growth and Obesity Chilean Cohort Study (GOCS). At 7 years, we measured waist
      circumference (WC) and blood glucose, insulin, triglycerides and high-density
      lipoprotein-cholesterol levels and constructed a metabolic risk score. We also
      measured percent fat mass (adiposity), plasma concentrations of leptin and
      adiponectin (adipose functionality) and bone age using wrist ultrasound (skeletal
      maturation). RESULTS: We found that 44% of the children had an AR <5 years.
      Earlier AR was associated with larger WC (beta: 5.10 (95% confidence interval
      (CI): 4.29-5.91)), higher glucose (beta: 1.02 (1.00-1.03)), insulin resistance
      (beta Homeostatic Model Assessment: 1.06 (1.03-1.09)), triglycerides (beta: 10.37
      (4.01-6.73)) and adverse metabolic score (beta: 0.30 (0.02-0.37)). Associations
      decreased significantly if adiposity was added to the models (i.e. beta WC: 0.85
      (0.33-1.38)) and, to a lesser extent, when adipokines (i.e. beta WC: 0.73 (0.14
      1.32)) and skeletal maturation (i.e. beta WC: 0.65 (0.10-1.20)) were added.
      CONCLUSION: In GOCS children, AR at a younger age predicts higher metabolic risk
      at 7 years; these associations are mostly explained by increased adiposity, but
      adipose dysfunction and accelerated skeletal maturation also have a role.

PMID- 24909828
TI  - Attentional impulsivity in binge eating disorder modulates response inhibition
      performance and frontal brain networks.
AB  - BACKGROUND: A subgroup of overweight and obese people is characterized by binge
      eating disorder (BED). Increased impulsivity has been suggested to cause binge
      eating and subsequent weight gain. In the current study, neuronal correlates of
      increased impulsivity in binge eating disorder during behavioral response
      inhibition were investigated. METHODS: Magnetic brain activity and behavioral
      responses of 37 overweight and obese individuals with and without diagnosed BED
      were recorded while performing a food-related visual go-nogo task. Trait
      impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). RESULTS:
      Specifically, increased attentional impulsiveness (a subscale of the BIS-11) in
      BED was related to decreased response inhibition performance and hypoactivity in
      the prefrontal control network, which was activated when response inhibition was
      required. Furthermore, participants with BED showed a trend for a food-specific
      inhibition performance decline. This was possibly related to the absence of a
      food-specific activity increase in the prefrontal control network in BED, as
      observed in the control group. In addition, an increase in activity related to
      the actual button press during prepotent responses and alterations in visual
      processing were observed. CONCLUSIONS: Our results suggest an attentional
      impulsiveness-related attenuation in response inhibition performance in
      individuals with BED. This might have been related to increased reward
      responsiveness and limited resources to activate the prefrontal control network
      involved in response inhibition. Our results substantiate the importance of
      neuronal markers for investigating prevention and treatment of obesity,
      especially in specific subgroups at risk such as BED.

PMID- 24909832
TI  - The mediating effect of self-evaluation bias of competence on the relationship
      between parental emotional support and children's academic functioning.
AB  - BACKGROUND: It is well established that children's self-evaluation bias of
      competence is related to the quality of parent-child emotional relationship. Such
      biases are linked to children's academic functioning and achievement. Links have
      also been established between the quality of parent-child emotional relationship
      and children's academic functioning. No study has yet explored how the effects of
      children's emotional relationship with their parents and children's self
      evaluation bias combine to explain their academic functioning. AIMS: The first
      goal was to examine whether the quality of parental emotional support reported by
      both children and parents was related to the children's self-evaluation bias of
      competence. The second goal was to examine the relationships between children's
      and parents' reports of emotional support, and children's academic functioning as
      measured by teachers' report of their motivation, self-regulation of school
      activities, and academic achievement. The third goal was to determine whether a
      children's self-evaluation bias mediated the relationship between parental
      emotional support and academic functioning. SAMPLE: In a 2-year longitudinal
      design, participants were 524 elementary pupils (grades 4 and 5), one of their
      parents, and their teachers. RESULTS: Our results indicated that a bias in self
      evaluation in the first year of the study mediated the relationship between the
      quality of parental emotional support assessed at the first year and their school
      functioning evaluated by their teacher 1 year later. CONCLUSION: The mediational
      model received clear support when it refers to the emotional support reported by
      children, but mixed support when reported by parents.

PMID- 24909829
TI  - A break in the obesity epidemic? Explained by biases or misinterpretation of the
      data?
AB  - Recent epidemiologic papers are presenting prevalence data suggesting breaks and
      decreases in obesity rates. However, before concluding that the obesity epidemic
      is not increasing anymore, the validity of the presented data should be discussed
      more thoroughly. We had a closer look into the literature presented in recent
      reviews to address the major potential biases and distortions, and to develop
      insights about how to interpret the presented suggestions for a potential break
      in the obesity epidemic. Decreasing participation rates, the use of reported
      rather than measured data and small sample sizes, or lack of representativeness,
      did not seem to explain presented breaks in the obesity epidemic. Further,
      available evidence does not suggest that stabilization of obesity rates is seen
      in higher socioeconomic groups only, or that urbanization could explain a
      potential break in the obesity epidemic. However, follow-ups of short duration
      may, in part, explain the apparent break or decrease in the obesity epidemic. On
      the other hand, a single focus on body mass index (BMI) ?25 or ?30 kg m(-)(2) is
      likely to mask a real increase in the obesity epidemic. And, in both children and
      adults, trends in waist circumferences were generally suggesting an increase, and
      were stronger than those reported for trends in BMI. Studies concluding that
      there is a recent break in the obesity epidemic need to be interpreted with
      caution. Reported studies presenting a break were mostly of short duration.
      Further, focusing on trends in waist circumference rather than BMI leads to a
      less optimistic conclusion: the public health problem of obesity is still
      increasing. 

PMID- 24909833
TI  - Where should we measure waist circumference in clinically overweight and obese
      youth?
AB  - AIMS: Waist circumference (WC) measurement is a useful tool in the assessment of
      overweight/obese individuals, but standard measures may miss an apron of
      'overhanging' fat (termed 'panniculus'). The objective of this study was to
      assess whether, in clinically overweight/obese youth, 'pannicular' WC better
      correlates with fat mass than a standard WC measurement. METHODS: Standard and
      pannicular WC, alongside body composition (BC) measures, were collected from 181
      consultations on 127 overweight and obese children/adolescents (52% male; mean
      (standard deviation) age 12.5 (3.4) years). Correlation coefficients describe
      associations between WC and measures of BC, and between DeltaWC and DeltaBC,
      while linear regression models assessed which of the WC measures explained more
      of the variability in BC and DeltaBC over time. RESULTS: Standard and pannicular
      WC were highly correlated (r = 0.95). Correlation coefficients with measures of
      BC were generally greater for pannicular than standard WC, with greatest
      correlations seen for whole body (r = 0.94 vs. 0.85, respectively) and truncal (r
      = 0.86 vs. 0.77) fat mass. Furthermore, pannicular and Deltapannicular WC
      explained more variability in truncal fat and Deltatruncal fat than the standard
      measure of WC. CONCLUSIONS: These data show that pannicular, rather than
      standard, WC measurements better correlate with absolute measures of fat mass,
      and their change over time, in clinically overweight/obese youth.

PMID- 24909831
TI  - Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric
      Crohn's disease.
AB  - Children and adolescents with Crohn's disease (CD) present often with a more
      complicated disease course compared to adult patients. In addition, the potential
      impact of CD on growth, pubertal and emotional development of patients underlines
      the need for a specific management strategy of pediatric-onset CD. To develop the
      first evidenced based and consensus driven guidelines for pediatric-onset CD an
      expert panel of 33 IBD specialists was formed after an open call within the
      European Crohn's and Colitis Organisation and the European Society of Pediatric
      Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough
      review of existing evidence a state of the art guidance on the medical treatment
      and long term management of children and adolescents with CD, with individualized
      treatment algorithms based on a benefit-risk analysis according to different
      clinical scenarios. In children and adolescents who did not have finished their
      growth, exclusive enteral nutrition (EEN) is the induction therapy of first
      choice due to its excellent safety profile, preferable over corticosteroids,
      which are equipotential to induce remission. The majority of patients with
      pediatric-onset CD require immunomodulator based maintenance therapy. The experts
      discuss several factors potentially predictive for poor disease outcome (such as
      severe perianal fistulizing disease, severe stricturing/penetrating disease,
      severe growth retardation, panenteric disease, persistent severe disease despite
      adequate induction therapy), which may incite to an anti-TNF-based top down
      approach. These guidelines are intended to give practical (whenever possible
      evidence-based) answers to (pediatric) gastroenterologists who take care of
      children and adolescents with CD; they are not meant to be a rule or legal
      standard, since many different clinical scenario exist requiring treatment
      strategies not covered by or different from these guidelines. 

PMID- 24909835
TI  - Clinical evaluation of a T. rubrum-specific polymerase chain reaction and
      pandermatophyte polymerase chain reaction in the diagnosis of suspected
      onychomycosis in 183 Serbian patients.

PMID- 24909834
TI  - Early changes in miRNA expression are predictive of response to extracorporeal
      photopheresis in cutaneous T-cell lymphoma.

PMID- 24909836
TI  - A randomized controlled trial of the effectiveness of a postnatal psychoeducation
      programme on outcomes of primiparas: study protocol.
AB  - AIM: To report a trial protocol that evaluates the effectiveness of postnatal
      psychoeducation programme in improving maternal parental self-efficacy and social
      support and in reducing postnatal depression among primiparas. BACKGROUND:
      Primiparas encounter physical, psychosocial and newborn care challenges in the
      early postnatal period. However, primiparas do not receive adequate professional
      support after early discharge from hospitals, thus hindering their adaptation to
      new role as mothers and smooth transition to motherhood. Postnatal
      psychoeducation programmes have been shown to be effective in improving pregnant
      women's health. However, there is a lack of theory-based, postnatal
      psychoeducation interventions for primiparas. DESIGN: A randomized controlled
      trial of two-group pretest and repeated posttests is proposed. METHODS: The study
      will recruit a minimum of 114 primiparas on the day of discharge from a
      Singaporean public hospital (protocol approved in May 2012). Eligible
      participants will be randomly allocated to either a control group (receiving
      routine care) or an experimental group (receiving a postnatal psychoeducation
      programme besides routine care). Outcome measures include maternal parental self
      efficacy, social support and postnatal depression. Data will be collected at
      baseline (on the day of discharge), 6 and 12 weeks postpartum. DISCUSSION: This
      will be the first study of its kind that will use rigorous study design to
      evaluate a theory-based innovative postnatal psychoeducation programme on
      maternal outcomes. The study may identify a potentially effective way of
      enhancing primiparas' self-efficacy and social support, which may in turn reduce
      their risk of postnatal depression. The Sigma Theta Tau International Upsilon Eta
      Chapter funded this study.

PMID- 24909837
TI  - Synergistic effect of cyclodextrins and methyl jasmonate on taxane production in
      Taxus x media cell cultures.
AB  - Methyl jasmonate and cyclodextrins are proven effective inducers of secondary
      metabolism in plant cell cultures. Cyclodextrins, which are cyclic
      oligosaccharides, can form inclusion complexes with nonhydrophilic secondary
      products, thus increasing their excretion from the producer cells to the culture
      medium. In the present work, using a selected Taxus x media cell line cultured in
      a two-stage system, the relationship between taxane production and the transcript
      profiles of several genes involved in taxol metabolism was studied to gain more
      insight into the mechanism by which these two elicitors regulate the biosynthesis
      and excretion of taxol and related taxanes. Gene expression was not clearly
      enhanced by the presence of cyclodextrins in the culture medium and variably
      induced by methyl jasmonate, but when the culture was supplemented with both
      elicitors, a synergistic effect on transcript accumulation was observed. The BAPT
      and DBTNBT genes, which encode the last two transferases involved in the taxol
      pathway, appeared to control limiting biosynthetic steps. In the cell cultures
      treated with both elicitors, the produced taxanes were found mainly in the
      culture medium, which limited retroinhibition processes and taxane toxicity for
      the producer cells. The expression level of a putative ABC gene was found to have
      increased, suggesting it played a role in the taxane excretion. Taxol
      biosynthesis was clearly increased by the joint action of methyl jasmonate and
      cyclodextrins, reaching production levels 55 times higher than in nonelicited
      cultures. 

PMID- 24909838
TI  - The transcriptome of lae1 mutants of Trichoderma reesei cultivated at constant
      growth rates reveals new targets of LAE1 function.
AB  - BACKGROUND: The putative methyltransferase LaeA is a global regulator that
      affects the expression of multiple secondary metabolite gene clusters in several
      fungi. In Trichoderma reesei, its ortholog LAE1 appears to predominantly regulate
      genes involved in increasing competitive fitness in its environment, including
      expression of cellulases and polysaccharide hydrolases. A drawback in all studies
      related to LaeA/LAE1 function so far, however, is that the respective loss-of
      function and overexpressing mutants display different growth rates. Thus some of
      the properties attributed to LaeA/LAE1 could be simply due to changes of the
      growth rate. RESULTS: We cultivated T. reesei, a Deltalae1 mutant and a lae1
      overexpressing strain in chemostats on glucose at two different growth rates
      (0.075 and 0.020 h-1) which resemble growth rates at repressing and derepressing
      conditions, respectively. Under these conditions, the effect of modulating LAE1
      expression was mainly visible in the Deltalae1 mutant, whereas the overexpressing
      strain showed little differences to the parent strain. The effect on the
      expression of some gene categories identified earlier (polyketide synthases,
      heterokaryon incompatibility proteins, PTH11-receptors) was confirmed, but in
      addition GCN5-N-acetyltransferases, amino acid permeases and flavin
      monooxygenases were identified as so far unknown major targets of LAE1 action.
      LAE1 was also shown to interfere with the regulation of expression of several
      genes by the growth rate. About a tenth of the genes differentially expressed in
      the Deltalae1 mutant under either growth condition were found to be clustered in
      the genome, but no specific gene group was associated with this phenomenon.
      CONCLUSIONS: Our data show that - using T. reesei LAE1 as a model - the
      investigation of transcriptome in regulatory mutants at constant growth rates
      leads to new insights into the physiological roles of the respective regulator.

PMID- 24909840
TI  - Relationship between the acyl chain length of paradol analogues and their
      antiobesity activity following oral ingestion.
AB  - 6-Paradol is known to activate thermogenesis in brown adipose tissue (BAT), and
      paradol analogues with different acyl chain lengths possess different pungency
      thresholds. In this study, the influence of the acyl chain length on the
      antiobesity activity of the paradol analogues was investigated. The antiobesity
      activity of 6-paradol in mice fed a high-fat diet for 8 weeks was greater than
      that of dihydrocapsiate. A comparison of the antiobesity activities of zingerone
      and 6-paradol showed that the length of the acyl chain in the paradol analogue
      was important for strong activity. Furthermore, the antiobesity activities of 6-,
      8-, and 12-paradol appeared to decrease in an acyl chain length-dependent manner.
      The mechanism of the antiobesity activity of 6-paradol was enhanced by increasing
      levels of energy metabolism in the BAT, as well as an increase in the expression
      of uncoupling proteins 1 via the activation of sympathetic nerve activity. 

PMID- 24909839
TI  - FAD binding, cobinamide binding and active site communication in the corrin
      reductase (CobR).
AB  - Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex
      coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic
      metabolic pathway. The aerobic synthesis involves reduction of the centrally
      chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before
      adenosylation can take place. A corrin reductase (CobR) enzyme has been
      identified as the likely agent to catalyse this reduction of the metal ion.
      Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin
      dinucleotide) and we also show that the enzyme can bind a corrin substrate
      consistent with its role in reduction of the cobalt of the corrin ring. Stopped
      flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides
      a potential link between the two electron reduction by NADH to the single
      electron reduction of Co(II) to Co(I). 

PMID- 24909841
TI  - Streptomyces sp. strain PGPA39 alleviates salt stress and promotes growth of
      'Micro Tom' tomato plants.
AB  - AIMS: To identify an actinobacterial strain that can promote growth and alleviate
      salinity stress in tomato plants. METHODS AND RESULTS: Actinobacteria were
      isolated from agricultural soil and screened for ACC deaminase activity,
      production of indole acetic acid (IAA), solubilization of tricalcium phosphate
      and sodium chloride (NaCl) salinity tolerance. Among the several strains tested,
      one strain designated PGPA39 exhibited higher IAA production, and phosphate
      solubilization in addition to ACC deaminase activity, and tolerance to 1 mol l(
      1) NaCl. Strain PGPA39 was identified as a Streptomyces strain based on 16S rDNA
      sequence and designated Streptomyces sp. strain PGPA39. It promoted the growth of
      Arabidopsis seedlings in vitro as evidenced by a significant increase in plant
      biomass and number of lateral roots. Salinity stress-alleviating activity of
      PGPA39 was evaluated using 'Micro Tom' tomato plants with 180 mmol l(-1) NaCl
      stress under gnotobiotic condition. A significant increase in plant biomass and
      chlorophyll content and a reduction in leaf proline content were observed in
      PGPA39-inoculated tomato plants under salt stress compared with control and salt
      stressed noninoculated plants. CONCLUSIONS: Streptomyces sp. strain PGPA39
      alleviated salt stress and promoted the growth of tomato plants. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study shows the potential of Streptomyces sp. strain
      PGPA39 in alleviating salinity stress in tomato plants and could be utilized for
      stress alleviation in crop plants under field conditions.

PMID- 24909842
TI  - Extreme temperature events alter demographic rates, relative fitness, and
      community structure.
AB  - The frequency and magnitude of extreme events are predicted to increase under
      future climate change. Despite recent advancements, we still lack a detailed
      understanding of how changes in the frequency and amplitude of extreme climate
      events are linked to the temporal and spatial structure of natural communities.
      To answer this question, we used a combination of laboratory experiments, field
      experiments, and analysis of multi-year field observations to reveal the effects
      of extreme high temperature events on the demographic rates and relative
      dominance of three co-occurrence aphid species which differ in their transmission
      efficiency of different agricultural pathogens. We then linked the geographical
      shift in their relative dominance to frequent extreme high temperatures through a
      meta-analysis. We found that both frequency and amplitude of extreme high
      temperatures altered demographic rates of species. However, these effects were
      species-specific. Increasing the frequency and amplitude of extreme temperature
      events altered which species had the highest fitness. Importantly, this change in
      relative fitness of species was consistent with significant changes in the
      relative dominance of species in natural communities in a 1 year long field
      heating experiment and 6 year long field survey of natural populations. Finally,
      at a global spatial scale, we found the same relationship between relative
      abundance of species and frequency of extreme temperatures. Together, our results
      indicate that changes in frequency and amplitude of extreme high temperatures can
      alter the temporal and spatial structure of natural communities, and that these
      changes are driven by asymmetric effects of high temperatures on the demographic
      rates and fitness of species. They also highlight the importance of understanding
      how extreme events affect the life-history of species for predicting the impacts
      of climate change at the individual and community level, and emphasize the
      importance of using a broad range of approaches when studying climate change.

PMID- 24909843
TI  - A biological market analysis of the plant-mycorrhizal symbiosis.
AB  - It has been argued that cooperative behavior in the plant-mycorrhizal mutualism
      resembles trade in a market economy and can be understood using economic tools.
      Here, we assess the validity of this "biological market" analogy by investigating
      whether a market mechanism--that is, competition between partners over the price
      at which they provide goods--could be the outcome of natural selection. Then, we
      consider the conditions under which this market mechanism is sufficient to
      maintain mutualistic trade. We find that: (i) as in a market, individuals are
      favored to divide resources among trading partners in direct relation to the
      relative amount of resources received, termed linear proportional discrimination;
      (ii) mutualistic trade is more likely to be favored when individuals are able to
      interact with more partners of both species, and when there is a greater relative
      difference between the species in their ability to directly acquire different
      resources; (iii) if trade is favored, then either one or both species is favored
      to give up acquiring one resource directly, and vice versa. We then formulate
      testable predictions as to how environmental changes and coevolved responses of
      plants and mycorrhizal fungi will influence plant fitness (crop yields) in
      agricultural ecosystems.

PMID- 24909844
TI  - Label-free logic modules and two-layer cascade based on stem-loop probes
      containing a G-quadruplex domain.
AB  - A simple, versatile, and label-free DNA computing strategy was designed by using
      toehold-mediated strand displacement and stem-loop probes. A full set of logic
      gates (YES, NOT, OR, NAND, AND, INHIBIT, NOR, XOR, XNOR) and a two-layer logic
      cascade were constructed. The probes contain a G-quadruplex domain, which was
      blocked or unfolded through inputs initiating strand displacement and the
      obviously distinguishable light-up fluorescent signal of G-quadruplex/NMM complex
      was used as the output readout. The inputs are the disease-specific nucleotide
      sequences with potential for clinic diagnosis. The developed versatile computing
      system based on our label-free and modular strategy might be adapted in multi
      target diagnosis through DNA hybridization and aptamer-target interaction. 

PMID- 24909845
TI  - Oxidation reduction is a key process for successful treatment of psoriasis by
      narrow-band UVB phototherapy.
AB  - Narrow-band UVB (NB-UVB) phototherapy is commonly used for treatment of
      psoriasis, though the mechanisms underlying its efficacy have not been completely
      elucidated. We used gene expression profiling to characterise gene expression in
      lesional epidermis from psoriasis patients in the middle and late stages of NB
      UVB photo-therapy. Increased melanogenesis gene expression was the earliest
      response to phototherapy. At the end of treatment, genes responding to
      phototherapy and correlated to treatment outcome were involved in oxidation
      reduction, growth and mitochondria organisation. Particularly, SPATA18, a key
      regulator of mitochondrial quality, was significantly down-regulated in psoriasis
      (p < 0.05). Poly(dA:dT) and poly(I:C) stimulation increased SPATA18 level in
      primary keratinocytes, indicating the importance of mitochondria quality control
      under innate immune induced oxidative stress. Normalised SPATA18 expression after
      phototherapy indicates improved mitochondrial quality control and restored
      cellular redox status. Our data suggest that oxidation reduction is critical for
      the resolution of psoriatic plaques following NB-UVB phototherapy. 

PMID- 24909846
TI  - Heteroatom-bridged tetraphenylenes: synthesis, structures, and properties.
AB  - Novel oxygen-, nitrogen-, sulfur-, and selenium-bridged tetraphenylenes were
      prepared from known tetraphenylene derivatives. Structures of these compounds
      were unambiguously confirmed by X-ray crystallographic analyses. Photophysical
      and electrochemical investigations of these heteroatom-bridged tetraphenylenes
      suggested their potential applications as electronic materials. 

PMID- 24909847
TI  - Orolingual angioedema after alteplase therapy of acute ischaemic stroke:
      incidence and risk of prior angiotensin-converting enzyme inhibitor use.
AB  - BACKGROUND AND PURPOSE: Orolingual angioedema (OA) is an uncommon but potentially
      life-threatening complication of treatment with recombinant tissue plasminogen
      activator (rt-PA; alteplase) during acute ischaemic stroke. This study aimed to
      determine the incidence of rt-PA-related OA in an Asian stroke population and the
      risk of pre-stroke anti-hypertensive drug use for development of this
      complication. METHODS: A multi-center stroke registry was used to identify the
      pre-stroke medications of acute ischaemic stroke patients receiving intravenous
      rt-PA from January 2002 to December 2013. The clinical manifestations of rt-PA
      related OA were recorded and the incidence of this complication was determined.
      The risks of pre-stroke use of different anti-hypertensive agents for the
      occurrence of rt-PA-related OA were determined from this study and from a meta
      analysis. RESULTS: A total of 559 patients received intravenous rt-PA over a 12
      year period. Five patients (two males) developed OA after rt-PA administration.
      The incidence of OA amongst these patients was 0.89% (95% confidence interval
      0.29%-2.09%), which was lower than that obtained by meta-analysis (1.9%). Amongst
      pre-stroke anti-hypertensive medications, angiotensin-converting enzyme (ACE)
      inhibitors were found in this study to have the highest relative risk for rt-PA
      related OA (17.1; 95% confidence interval 3.0-96.9). Meta-analysis also revealed
      that pre-stroke use of ACE inhibitors was associated with a high relative risk of
      OA after intravenous rt-PA (12.9; 95% confidence interval 4.5-37.0). CONCLUSIONS:
      The incidence of rt-PA-related OA in the Asian population is lower than that in
      the Caucasian population. Pre-stroke use of ACE inhibitors significantly
      increases the risk of this complication.

PMID- 24909848
TI  - Abstracts from the 2nd International Joined OTIS - ENTIS Conference, September 18
      21, 2014, Toronto, Canada.

PMID- 24909849
TI  - The (PrS/HGF-pDNA) multilayer films for gene-eluting stent coating: Gene
      protecting, anticoagulation, antibacterial properties, and in vivo antirestenosis
      evaluation.
AB  - Vascular gene-eluting stents (GES) is a promising strategy for treatment of
      cardiovascular disease. Very recently, we have proved that the (protamine
      sulfate/plasmid DNA encoding hepatocyte growth factor) (PrS/HGF-pDNA) multilayer
      can serve as a powerful tool for enhancing competitiveness of endothelial cell
      over smooth muscle cell, which opens perspectives for the regulation of
      intercellular competitiveness in the field of interventional therapy. However,
      before the gene multilayer films could be used in vascular stents for real
      clinical application, the preservation of gene bioactivity during the industrial
      sterilization and the hemocompatibility of film should be taken into account.
      Actually, both are long been ignored issues in the field of gene coating for GES.
      In this study, we demonstrate that the (PrS/HGF-pDNA) multilayer film exhibits
      the good gene-protecting abilities, which is confirmed by using the industrial
      sterilizations (gamma irradiation and ethylene oxide) and a routine storage
      condition (dry state at 4 degrees C for 30 days). Furthermore, hemocompatible
      measurements (such as platelet adhesion and whole blood coagulation) and
      antibacterial assays (bacteria adhesion and growth inhibition) indicate the good
      anticoagulation and antibacterial properties of the (PrS/HGF-pDNA) multilayer
      film. The in vivo preliminary data of angiography and histological analysis
      suggest that the (PrS/HGF-pDNA) multilayer coated stent can reduce the in-stent
      restenosis. This work reveals that the (PrS/HGF-pDNA) multilayer film could be a
      promising candidate as coating for GES, which is of great potential in future
      clinic application.

PMID- 24909850
TI  - Unified physicochemical property estimation relationships (UPPER).
AB  - The knowledge of physicochemical properties of organic compounds becomes
      increasingly important in pharmaceutical sciences, chemical engineering, and
      other fields. In this study, we developed UPPER (Unified Physicochemical Property
      Estimation Relationships), a comprehensive model for the estimation of 20
      physicochemical properties of organic compounds. UPPER is a system of
      thermodynamically sound relationships that relate the various phase-transition
      properties to one another, which includes transition heats, transition entropies,
      transition temperatures, molar volume, vapor pressure, solubilities and partition
      coefficients in different solvents, and so on. UPPER integrates group
      contributions with the molecular geometric factors that affect transition
      entropies. All of the predictions are directly based on molecular structure. As a
      result, the proposed model provides a simple and accurate prediction of the
      properties studied. UPPER is designed to predict industrially, pharmaceutically,
      and environmentally relevant physicochemical properties. It can be an aid for the
      efficient design and synthesis of compounds with optimal physicochemical
      properties.

PMID- 24909852
TI  - Dynamic complexation of copper(I) chloride by carbene-stabilized disilicon.
AB  - Reaction of N-heterocyclic-carbene (NHC)-stabilized disilicon (1) with CuCl gave
      a carbene-stabilized disilicon-copper(I) chloride complex (2). The nature of the
      structure and bonding in 2 has been investigated by crystallographic,
      spectroscopic, and computational methods. The dynamic complexation behavior of 2
      was experimentally explored by variable-temperature NMR analysis. 

PMID- 24909851
TI  - Alpha C-telopeptide of type I collagen is associated with subchondral bone
      turnover and predicts progression of joint space narrowing and osteophytes in
      osteoarthritis.
AB  - OBJECTIVE: To evaluate joint tissue remodeling using the urinary collagen
      biomarkers urinary alpha-C-telopeptide of type I collagen (alpha-CTX) and urinary
      C-telopeptide of type II collagen (CTX-II) and to determine the association of
      these biomarkers with osteoarthritis (OA) severity, progression, and localized
      knee bone turnover. METHODS: Participants (n = 149) with symptomatic and
      radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3
      years, and late-phase bone scintigraphy of both knees at baseline, which were
      scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity
      and uptake intensity, with scores summed across knees. Urinary concentrations of
      alpha-CTX and CTX-II were determined by enzyme-linked immunosorbent assay.
      Immunohistochemical analysis of human OA knees was performed to localize the
      joint tissue origin of the biomarker epitopes. RESULTS: Urinary alpha-CTX
      concentrations correlated strongly with the intensity of bone scintigraphic
      uptake and with JSN progression (risk ratio 13.2) and osteophyte progression
      (risk ratio 3). Urinary CTX-II concentrations were strongly associated with
      intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and
      with OA progression based on osteophyte score. Urinary alpha-CTX localized
      primarily to high bone turnover areas in subchondral bone. CTX-II localized to
      the bone-cartilage interface, the tidemark, and damaged articular cartilage.
      CONCLUSION: Baseline urinary alpha-CTX, which was localized to high turnover
      areas of subchondral bone, was associated with dynamic bone turnover of knees, as
      signified by scintigraphy, and progression of both osteophytes and JSN. Urinary
      CTX-II correlated with JSN and osteophyte severity and progression of
      osteophytes. To our knowledge, this represents the first report of serologic
      markers reflecting subchondral bone turnover. These collagen markers may be
      useful for noninvasive detection and quantification of active subchondral bone
      turnover and joint remodeling in knee OA.

PMID- 24909854
TI  - Photoperiodic regulation of FGF21 production in the Siberian hamster.
AB  - This article is part of a Special Issue "Energy Balance". FGF21 is an endocrine
      member of the fibroblast growth factor superfamily that has been shown to play an
      important role in the physiological response to nutrient deprivation. Food
      restriction enhances hepatic FGF21 production, which serves to engage an
      integrated response to energy deficit. Specifically, elevated FGF21 levels lead
      to reduced gluconeogenesis and increased hepatic ketogenesis. However,
      circulating FGF21 concentrations also paradoxically rise in states of metabolic
      dysfunction such as obesity. Furthermore, multiple peripheral tissues also
      produce FGF21 in addition to the liver, raising questions as to its endocrine and
      paracrine roles in the control of energy metabolism. The objectives of this study
      were to measure plasma FGF21 concentrations in the Siberian hamster, a rodent
      which undergoes a seasonal cycle of fattening and body weight gain in the long
      days (LD) of summer, followed by reduction of appetite and fat catabolism in the
      short days (SD) of winter. Groups of adult male hamsters were raised in long
      days, and then exposed to SD for up to 12 weeks. Chronic exposure of LD animals
      to SD led to a significant increase in circulating FGF21 concentrations. This
      elevation of circulating FGF21 was preceded by an increase in liver FGF21 protein
      production evident as early as 4 weeks of exposure to SD. FGF21 protein abundance
      was also increased significantly in interscapular brown adipose tissue, with a
      positive correlation between plasma levels of FGF21 and BAT protein abundance
      throughout the experimental period. Epididymal white adipose tissue and skeletal
      muscle (gastrocnemius) also produced FGF21, but levels did not change in response
      to a change in photoperiod. In summary, a natural programmed state of fat
      catabolism was associated with increased FGF21 production in the liver and BAT,
      consistent with the view that FGF21 has a role in adapting hamsters to the
      hypophagic winter state.

PMID- 24909853
TI  - The impact of engagement in street-based income generation activities on
      stimulant drug use cessation among people who inject drugs.
AB  - BACKGROUND: Despite the growing prevalence of illicit stimulant drug use
      internationally, and the widespread involvement of people who inject drugs (IDU)
      within street-based drug markets, little is known about the impact of different
      types of street-based income generation activities on the cessation of stimulant
      use among IDU. METHODS: Data were derived from an open prospective cohort of IDU
      in Vancouver, Canada. We used Kaplan-Meier methods and Cox proportional hazards
      regression to examine the effect of different types of street-based income
      generation activities (e.g., sex work, drug dealing, and scavenging) on time to
      cessation of stimulant use. RESULTS: Between December, 2005 and November, 2012,
      887 IDU who use stimulant drugs (cocaine, crack cocaine, or crystal
      methamphetamine) were prospectively followed-up for a median duration of 47
      months. In Kaplan-Meier analyses, compared to those who did not engage in street
      based income generation activities, participants who reported sex work, drug
      dealing, scavenging, or more than one of these activities were significantly less
      likely to report stimulant drug use cessation (all p<0.001). When considered as
      time-updated variables and adjusted for potential confounders in a multivariable
      model, each type of street-based income generation activity remained
      significantly associated with a slower time to stimulant drug cessation (all
      p<0.005). CONCLUSIONS: Our findings highlight the urgent need for strategies to
      address stimulant dependence, including novel pharmacotherapies. Also important,
      structural interventions, such as low-threshold employment opportunities,
      availability of supportive housing, legal reforms regarding drug use, and
      evidence-based approaches that reduce harm among IDU are urgently required.

PMID- 24909855
TI  - A familial heterozygous null mutation of MET in autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) results from interactions of genetic and
      environmental factors. The MET proto-oncogene has been identified as a candidate
      gene for autism susceptibility, and is implicated in neurodevelopment and social
      brain circuitry. Here, we describe the first case of a familial mutation of MET,
      consisting of an interstitial genomic deletion removing exons 12 through 15,
      causing a frameshift and premature stop codon, with evidence of nonsense-mediated
      mRNA decay. On the other allele, patients carried the C allele of the MET
      promoter rs1858830 polymorphism, known to decrease MET expression and previously
      associated with autism susceptibility. The heterozygous mutation was associated
      with autism in one patient, and language and social impairment in a sibling. Our
      observations delineate the phenotypic spectrum associated with a clearly defined,
      very likely complete loss of function mutation of MET. Incomplete penetrance in
      this family was consistent with MET as a partial susceptibility gene for ASD.
      Implication of MET in normal and pathological brain development opens new
      perspectives for understanding the pathophysiology of autism and for eventual
      therapeutical clues.

PMID- 24909856
TI  - A reporter-targeted approach to reducing the use of the term "superficial femoral
      vein" in ultrasound reports for deep vein thrombosis.
AB  - BACKGROUND: The term "superficial femoral vein" is felt to be potentially
      misleading and dangerous in the context of deep venous thrombosis (DVT) of the
      lower limb, with the preferred term now being "femoral vein." The purpose of this
      work was to identify a means of reducing its use in reports of lower limb
      sonographic scans for DVT. METHODS: A retrospective search of the reports for all
      lower limb sonographic scans for the detection of DVT in 2011 was performed using
      the Radiology Information System to identify the baseline rate of use of the
      term. Nontargeted and subsequently targeted e-mails were then sent to reporters
      of such sonographic scans over a 6-month follow-up period, and the results were
      reevaluated. RESULTS: The baseline rate of use of the term was 17% before any
      intervention. It decreased to 10% following nontargeted intervention, and to 6%
      following targeted e-mail intervention. There were no cases of patients coming to
      harm as a result of the use of the term during the study period. CONCLUSIONS: A
      simple and inexpensive system of e-mails to reporters resulted in a decline in
      the rate of use of the misleading term "superficial femoral vein."

PMID- 24909857
TI  - Evaluation of anterior chamber angle under dark and light conditions in angle
      closure glaucoma: An anterior segment OCT study.
AB  - AIM: To evaluate changes of nasal and temporal anterior chamber angle (ACA) in
      subjects with angle closure glaucoma using Spectralis AS-OCT (SAS-OCT) under dark
      and light conditions. METHODS: Based on dark-room gonioscopy, 24 subjects with
      open angles and 86 with narrow angles participated in this study. The nasal and
      temporal angle opening distance at 500 MUm anterior to the scleral spur (AOD500),
      nasal and temporal ACA were measured using SAS-OCT in light and dark conditions.
      RESULT: In 2 groups, ACA and AOD500 in nasal and temporal quadrants were
      significantly greater in light compared to dark (all with p=0.000). The AOD500
      and ACA were significantly higher in nasal than temporal in measured conditions
      for 2 groups except the ACA and AOD500 of normal group measured in light. The
      difference between nasal and temporal in dark (29.07 +/- 65.71 MUm for AOD500 and
      5.7 +/- 4.07 degrees  for ACA) was greater than light (24.86 +/- 79.85 MUm for
      AOD500 and 2.09 +/- 7.21 degrees  for ACA) condition. But the difference was only
      significant for ACA (p=0.000). The correlation analysis showed a negative
      correlation between AOD500 and pupil diameter in temporal and nasal quadrants
      (both with p=0.000). While temporal AOD500 difference correlated with spherical
      equivalent, temporal and asal gonioscopy, nasal AOD correlated with IOP, temporal
      and nasal gonioscopy. CONCLUSIONS: Clinically important changes in ACA structure
      could be detected with SAS-OCT in nasal and temporal quadrants under different
      illumination intensity. The results could help in improvement of examination
      condition for better and more accurate assessment of individuals with angle
      closure glaucoma.

PMID- 24909858
TI  - Quantitative proteomics identifies unanticipated regulators of nitrogen- and
      glucose starvation.
AB  - The molecular mechanisms underlying how cells sense, respond, and adapt to
      alterations in nutrient availability have been studied extensively during the
      past years. While most of these studies have focused on the linear connections
      between signaling components, it is increasingly being recognized that signaling
      pathways are interlinked in molecular circuits and networks such that any
      metabolic perturbation will induce signaling-wide ripple effects. In the present
      study, we have used quantitative mass spectrometry (MS) to examine how the yeast
      Saccharomyces cerevisiae responds to nitrogen- or glucose starvation. We identify
      nearly 1400 phosphorylation sites of which more than 500 are regulated in a
      temporal manner in response to glucose- or nitrogen starvation. By bioinformatics
      and network analyses, we have identified the cyclin-dependent kinase (CDK)
      inhibitor Sic1, the Hsp90 co-chaperone Cdc37, and the Hsp90 isoform Hsp82 to
      putatively mediate some of the starvation responses. Consistently, quantitative
      expression analyses showed that Sic1, Cdc37, and Hsp82 are required for normal
      expression of nutrient-responsive genes. Collectively, we therefore propose that
      Sic1, Cdc37, and Hsp82 may orchestrate parts of the cellular starvation response
      by regulating transcription factor- and kinase activities. 

PMID- 24909859
TI  - Dual pH-triggered multistage drug delivery systems based on host-guest
      interaction-associated polymeric nanogels.
AB  - The polymeric nanogels were constructed via host-guest interactions for dual pH
      triggered multistage drug delivery, which showed tumor acidity-triggered nanogel
      reorganization into smaller nanoparticles for deep tissue penetration, high
      efficiency cellular uptake, and intracellular endo-lysosomal pH-responsive drug
      release. 

PMID- 24909860
TI  - Social stressors and cardiovascular response: influence of ambivalent
      relationships and behavioral ambivalence.
AB  - OBJECTIVE: The protective influence of social relationships on health is well
      documented; however, not all relationships are positive and negative aspects of
      relationships may be detrimental. Relatively less is known about the
      relationships characterized by both positivity and negativity (i.e.,
      ambivalence). The goal of this study was to examine the relative influence of
      ambivalence in relationship quality and social behavior on cardiovascular
      response. METHODS: 104 healthy young adults were randomly assigned to bring in
      either a supportive or ambivalent same-sex friend to the experiment. Participants
      were also randomly assigned to receive positive, negative, ambivalent or
      ambiguous feedback from their friend after giving a series of speeches.
      Cardiovascular response was obtained before, during, and after the social
      stressor (speech task). RESULTS: Results indicate a significant effect of
      relationship type before, during, and after the stressor task. Adjusting for
      baseline, heart rate reactivity and anxiety was significantly higher among those
      assigned to ambivalent friends relative to those assigned to supportive friends
      during the stressor task (ps<.05). There was also a significant effect of
      behavioral feedback during the speech task, such that those receiving ambivalent
      messages had the greatest systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) reactivity (p<.05); however, there was no interaction between
      relationship and feedback conditions. Those in the ambivalent friend condition
      also exhibited significantly higher SBP, DBP, and anxiety during the baseline and
      recovery periods (ps<.05). CONCLUSIONS: These findings suggest that both
      relationship quality and the actions of relationships may have a significant
      influence on health-relevant physiology.

PMID- 24909861
TI  - Auger recombination of biexcitons and negative and positive trions in individual
      quantum dots.
AB  - Charged exciton states commonly occur both in spectroscopic studies of quantum
      dots (QDs) and during operation of QD-based devices. The extra charge added to
      the neutral exciton modifies its radiative decay rate and also opens an
      additional nonradiative pathway associated with an Auger process whereby the
      recombination energy of an exciton is transferred to the excess charge. Here we
      conduct single-dot spectroscopic studies of Auger recombination in thick-shell
      ("giant") CdSe/CdS QDs with and without an interfacial alloy layer using time
      tagged, time-correlated single-photon counting. In photoluminescence (PL)
      intensity trajectories of some of the dots, we resolve three distinct states of
      different emissivities ("bright", "gray", and "dark") attributed, respectively,
      to the neutral exciton and negative and positive trions. Simultaneously acquired
      PL lifetime trajectories indicate that the positive trion is much shorter lived
      than the negative trion, which can be explained by a high density of valence band
      states and a small hole localization radius (defined by the QD core size),
      factors that favor an Auger process involving intraband excitation of a hole. A
      comparison of trion and biexciton lifetimes suggests that the biexciton Auger
      decay can be treated in terms of a superposition of two independent channels
      associated with positive- and negative-trion pathways. The resulting
      interdependence between Auger time constants might simplify the studies of
      multicarrier recombination by allowing one, for example, to infer Auger lifetimes
      of trions of one sign based on the measurements of biexciton decay and dynamics
      of the trions of the opposite sign or, alternatively, estimate the biexciton
      lifetime based on studies of trion dynamics. 

PMID- 24909862
TI  - Are independent mobility and territorial range associated with park visitation
      among youth?
AB  - BACKGROUND: Parks are important for providing opportunities for physical activity
      among youth. Apart from engaging in physical activity whilst visiting a park,
      active transportation (e.g. walking or cycling) to parks is potentially an
      additional source of physical activity. Previous research has shown that a major
      barrier to young people visiting parks is their inability to visit parks
      unaccompanied by an adult. It is not known; however, whether young people who
      have greater independent mobility and territorial range (ability to move around
      their neighbourhood alone or with friends, unaccompanied by an adult) are more
      likely to visit parks. This study examined park visitation and travel mode to
      parks and whether independent mobility and territorial range were associated with
      park visitation among youth living in disadvantaged areas of Victoria, Australia.
      METHODS: In 2010-11, 311 youth aged 8-16 years self-reported their park use,
      active transport, independent mobility to parks, and territorial range. Logistic
      regression models determined the odds of park visitation (once per week or more)
      according to independent mobility and territorial range, adjusting for key
      covariates. RESULTS: Overall, 75% of participants reported visiting parks, and
      37% visited their 'usual' park at least once per week. Of those who reported
      visiting parks, 87% travelled to the park they usually visited using active
      transport: 57% walked, 22% cycled, and 8% used a scooter/skateboard. Just 15% and
      13% of youth regularly walked or cycled alone to parks/playgrounds respectively,
      and 25% and 19% regularly walked or cycled with friends or siblings (no adults)
      respectively. For the 84% who reported having parks/playgrounds within walking
      distance from home, those who regularly walked alone to parks (OR 3.61; CI=1.67,
      7.80), and regularly walked (OR 2.27; CI=1.14, 4.55) or cycled (OR 3.38; CI=1.73,
      6.62) with friends to parks, were significantly more likely to visit a park at
      least once per week, compared to others. CONCLUSIONS: This study showed that
      active transport is frequently used by this sample of young people to travel to
      parks. Findings also highlight the potential importance of providing
      opportunities for youth aged 8-16 years to visit local parks independent of an
      adult.

PMID- 24909863
TI  - Arterial stiffness, oxidative stress, and smoke exposure in wildland
      firefighters.
AB  - OBJECTIVES: To assess the association between exposure, oxidative stress,
      symptoms, and cardiorespiratory function in wildland firefighters. METHODS: We
      studied two Interagency Hotshot Crews with questionnaires, pulse wave analysis
      for arterial stiffness, spirometry, urinary 8-iso-prostaglandin F2alpha (8
      isoprostane) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and the smoke exposure
      marker (urinary levoglucosan). Arterial stiffness was assessed by examining
      levels of the aortic augmentation index, expressed as a percentage. An oxidative
      stress score comprising the average of z-scores created for 8-OHdG and 8
      isoprostane was calculated. RESULTS: Mean augmentation index % was higher for
      participants with higher oxidative stress scores after adjusting for smoking
      status. Specifically for every one unit increase in oxidative stress score the
      augmentation index % increased 10.5% (95% CI: 2.5, 18.5%). Higher mean lower
      respiratory symptom score was associated with lower percent predicted forced
      expiratory volume in one second/forced vital capacity. CONCLUSIONS: Biomarkers of
      oxidative stress may serve as indicators of arterial stiffness in wildland
      firefighters.

PMID- 24909864
TI  - Assessment of the best N(3-) donors in preparation of [M(N)(PNP)]-based
      (M=(99m)Tc-; (188)Re) target-specific radiopharmaceuticals: Comparison among
      succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and
      PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ).
AB  - Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and
      PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ) are nitrido
      nitrogen atom donors employed for the preparation of nitride [M(N)]-complexes
      (M=(99m)Tc and (188)Re). This study aims to compare the capability and the
      efficiency of these three N(3-) group donors, in the preparation of [M(N)PNP]
      based target-specific compounds (M=(99m)Tc, (188)Re; PNP=aminodiphosphine). For
      this purpose, three different kit formulations (SDH kit; HO2C-PEG600-DTCZ kit;
      HDTCZ kit) were assembled and used in the preparation of [M(N)(cys~)(PNP3)](0/+)
      complexes (cys~=cysteine derivate ligands). For each formulation, the
      radiochemical yield (RCY) of the [M(N)(~cys)(PNP3)] compounds, was determined by
      HPLC. The deviation of the percentage of RCY, due to changes in concentration of
      the N(3-) donors and of the exchanging ligand, was determined. For (99m)Tc, data
      clearly show that HDTCZ is the most efficient donor of N(3-); however, SDH is the
      most suitable nitrido nitrogen atom donor for the preparation of
      [(99m)Tc(N)(PNP)]-based target-specific agents with high specific activity. When
      HO2C-PEG600-DTCZ or HDTCZ are used in N(3-) donation, high amounts of the
      exchanging ligand (10(-4)M) were required for the formation of the final complex
      in acceptable yield. The possibility to use microgram amounts of HDTCZ also in
      [(188)Re(N)] preparation (0.050mg) reduces its ability to compete in ligand
      exchange reactions, minimizing the quantity of chelators required to obtain the
      final complex in high yield. This finding can be exploit for increasing the
      radiolabeling efficiency in [(188)Re(N)]-radiopharmaceutical preparations
      compared to the previously reported HDTCZ-based procedure, notwithstanding a
      purification process could be necessary to improve the specific activity of the
      complexes. 

PMID- 24909866
TI  - How a "pinch of salt" can tune chaotic mixing of colloidal suspensions.
AB  - Efficient mixing of colloids, particles or molecules is a central issue in many
      processes. It results from the complex interplay between flow deformations and
      molecular diffusion, which is generally assumed to control the homogenization
      processes. In this work we demonstrate on the contrary that despite fixed flow
      and self-diffusion conditions, the chaotic mixing of colloidal suspensions can be
      either boosted or inhibited by the sole addition of a trace amount of salt as a
      co-mixing species. Indeed, this shows that local saline gradients can trigger a
      chemically driven transport phenomenon, diffusiophoresis, which controls the rate
      and direction of molecular transport far more efficiently than the usual Brownian
      diffusion. A simple model combining the elementary ingredients of chaotic mixing
      with diffusiophoretic transport of the colloids allows rationalization of our
      observations and highlights how small-scale out-of-equilibrium transport bridges
      to mixing at much larger scales in a very effective way. Considering chaotic
      mixing as a prototypal building block for turbulent mixing suggests that these
      phenomena, occurring whenever the chemical environment is inhomogeneous, might
      bring interesting perspectives from micro-systems to large-scale situations, with
      examples ranging from ecosystems to industrial contexts. 

PMID- 24909865
TI  - Simultaneous ECG-gated PET imaging of multiple mice.
AB  - INTRODUCTION: We describe and illustrate a method for creating ECG-gated PET
      images of the heart for each of several mice imaged at the same time. The method
      is intended to increase "throughput" in PET research studies of cardiac dynamics
      or to obtain information derived from such studies, e.g. tracer concentration in
      end-diastolic left ventricular blood. METHODS: An imaging bed with provisions for
      warming, anesthetic delivery, etc., was fabricated by 3D printing to allow
      simultaneous PET imaging of two side-by-side mice. After electrode attachment,
      tracer injection and placement of the animals in the scanner field of view, ECG
      signals from each animal were continuously analyzed and independent trigger
      markers generated whenever an R-wave was detected in each signal. PET image data
      were acquired in "list" mode and these trigger markers were inserted into this
      list along with the image data. Since each mouse is in a different spatial
      location in the FOV, sorting of these data using trigger markers first from one
      animal and then the other yields two independent and correctly formed ECG-gated
      image sequences that reflect the dynamical properties of the heart during an
      "average" cardiac cycle. RESULTS: The described method yields two independent ECG
      gated image sequences that exhibit the expected properties in each animal, e.g.
      variation of the ventricular cavity volumes from maximum to minimum and back
      during the cardiac cycle in the processed animal with little or no variation in
      these volumes during the cardiac cycle in the unprocessed animal. CONCLUSION: ECG
      gated image sequences for each of several animals can be created from a single
      list mode data collection using the described method. In principle, this method
      can be extended to more than two mice (or other animals) and to other forms of
      physiological gating, e.g. respiratory gating, when several subjects are imaged
      at the same time.

PMID- 24909868
TI  - Overuse of fluoroscopic gastrostomy studies in a children's hospital.
AB  - BACKGROUND: Gastrostomy tubes are often dislodged or exchanged in children.
      Indications for fluoroscopic examination of gastrostomy location include concern
      for malposition, dislodgement, leak, or gastric outlet obstruction. We
      hypothesized that most of the studies obtained at our institution were not
      ordered for one of the aforementioned indications and do not ultimately affect
      patient management. METHODS: All fluoroscopic gastrostomy studies performed from
      January 2011 to December 2012 were reviewed. Transgastric jejunostomy studies
      were excluded. Patient demographics, indications for the study, elapsed time
      since placement, imaging findings, and short-term outcomes were recorded. Chi
      square analysis was used to evaluate relationships between categorical variables.
      RESULTS: During the study period, 337 patients who underwent fluoroscopic
      gastrostomy studies were identified; median age was 2.5 y (0.05-23.8). Sixty-two
      percent (208/337) of the studies were ordered in asymptomatic patients to confirm
      tube placement location after routine exchange or replacement. Symptomatic
      patients accounted for 38% of the studies. Ordering physicians were primarily
      nonsurgeons (72%, 242/337). Abnormal findings were observed in 4.8% (16/337) of
      patients, six (1.7%) of whom required an operative intervention. The 2.9% (6/208)
      abnormal study rate for asymptomatic patients was significantly lower than the
      7.9% (10/129) rate in the patients who were evaluated for symptomatic indications
      (P = 0.03). CONCLUSIONS: Most of the fluoroscopic gastrostomy studies ordered at
      a tertiary care center did not appear to alter patient care. Development of a
      standardized management algorithm based on clinical indications is necessary to
      decrease the number of extraneous gastrostomy studies.

PMID- 24909867
TI  - Validation of the University HealthSystem Consortium administrative dataset:
      concordance and discordance with patient-level institutional data.
AB  - BACKGROUND: The University HealthSystem Consortium Clinical Database-Resource
      Manager (UHC CD-RM) is an administrative database increasingly queried for both
      research and administrative purposes, but it has not been comprehensively
      validated. To address this knowledge gap, we compared the UHC CD-RM with an
      institutional dataset to determine its validity and accuracy. MATERIALS AND
      METHODS: Age, gender, and date of operation were used to identify patients
      undergoing pancreaticoduodenectomy from 2009-2011 in both the UHC CD-RM and our
      institutional pancreatic surgery database. Patient- and intervention-specific
      variables including perioperative mortality, complications, length of stay,
      discharge disposition, and readmission were compared between datasets. RESULTS: A
      total of 107 UHC CD-RM and 105 institutional patients met inclusion criteria. In
      both datasets 103 matched cases were present. Between the 103 matched cases,
      there was concordance with respect to median age (P = 0.87), gender (P = 0.89),
      race (P = 0.84), overall length of stay (P = 0.46), discharge disposition (P =
      0.95), 30-d readmission rate (P = 0.87), and 30-d mortality (P = 0.70). Most
      comorbidities and complications were captured; however, several disease-specific
      complications were absent within the UHC CD-RM. CONCLUSIONS: Most of the
      clinically significant patient- and intervention-specific variables within the
      UHC CD-RM are reliably reported. With recognition of its limitations, the UHC CD
      RM is a reliable surrogate for institutional medical records and should be
      considered a valuable research tool for health service researchers.

PMID- 24909869
TI  - Smooth muscle actin as a novel serologic marker of severe intestinal damage in
      rat intestinal ischemia-reperfusion and human necrotising enterocolitis.
AB  - BACKGROUND: Despite emergence of markers of intestinal mucosal damage such as
      intestinal fatty-acid binding protein (i-FABP), there are no specific markers of
      damage extending into the muscle layers. We hypothesized that smooth muscle actin
      (SMA) released from the intestinal muscularis would be detectable in plasma after
      severe intestinal injury. MATERIALS AND METHODS: Serial blood samples were
      collected from rats (n = 10) undergoing intestinal ischemia-reperfusion injury
      (IRI) and controls (n = 5). Additionally, admission and/or preoperative plasma
      samples were collected from twelve neonates with necrotizing enterocolitis (NEC),
      and five age- and weight-matched controls. Plasma ileal fatty-acid binding
      protein (rat) or i-FABP (human) were measured by enzyme-linked immunosorbent
      assay, and plasma SMA was detected by western blotting. RESULTS: Plasma ileal
      fatty-acid binding protein was low in both the control group and IRI at baseline,
      but became rapidly elevated in the IRI group even during ischemia. SMA was
      detected in reperfusion plasma samples of all IRI rats, but in none of the
      control samples. Plasma i-FABP was higher in infants with NEC than age- and
      weight-matched controls. Although i-FABP was higher in infants with severe
      surgical disease compared with focal disease, there was no difference between the
      operative and nonoperative groups. SMA was detected in the plasma of all four
      neonates with severe surgical NEC, but not in those with focal disease or those
      who were successfully conservatively managed. CONCLUSIONS: SMA is detectable in
      plasma after severe intestinal injury and maybe a clinically useful maker of
      intestinal muscle damage.

PMID- 24909870
TI  - Outer membrane vesicles alter inflammation and coagulation mediators.
AB  - INTRODUCTION: Outer membrane vesicles (OMVs) were previously shown to be capable
      of initiating the inflammatory response seen in the transition of an infection to
      sepsis. However, another tenet of sepsis is the development of a hypercoagulable
      state and the role of OMVs in the development of this hypercoagulability has not
      been evaluated. The objective of this study was to evaluate the ability of OMVs
      to elicit endothelial mediators of coagulation and inflammation and induce
      platelet activation. METHODS: Human umbilical vein endothelial cells (HUVECs)
      were incubated with OMVs and were analyzed for the expression of tissue factor
      (TF), thrombomodulin, and the adhesion molecules P-selectin and E-selectin.
      Supernatants of OMV-treated HUVECs were mixed with whole blood and assessed for
      prothrombotic monocyte-platelet aggregates (MPA). RESULTS: OMVs induce
      significantly increased expression of TF, E-selectin, and P-selectin, whereas,
      the expression of thrombomodulin by HUVECs is significantly decreased (P < 0.05).
      The lipopolysaccharide inhibitor clearly inhibited the expression of E-selectin
      following incubation with OMVs, although its impact on TF and thrombomodulin
      expression was nominal. Incubation of whole blood with supernatant from HUVECs
      exposed to OVMs resulted in increased MPAs. CONCLUSIONS: This study demonstrates
      that, at the cellular level, OMVs from pathogenic bacteria play a complex role in
      endothelial activation. Although OMV-bound lipopolysaccharide modulates
      inflammatory proteins, including E-selectin, it has a negligible effect on the
      tested coagulation mediators. Additionally, endothelial activation by OMVs
      facilitates platelet activation as indicated by increased MPAs. By influencing
      the inflammatory and coagulation cascades, OMVs may contribute to the
      hypercoagulable response seen in sepsis.

PMID- 24909871
TI  - Epithelial cell adhesion molecule is a prognosis marker for intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: Recently, we identified a gene signature of intrahepatic
      cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for
      prognosis. The most upregulated genes included epithelial cell adhesion molecule
      (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC
      biomarkers could predict recurrence of resected ICC. METHODS: Both functional
      analysis of the stroma signature previously obtained and immunohistochemistry of
      40 resected ICC were performed. The relationships between the expression of CSC
      markers and clinicopathologic factors including survival were assessed by
      univariate and multivariable analyzes. RESULTS: Gene expression profile of the
      stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on
      tissue microarray showed at a protein level the increased expression of CSC
      biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The
      overexpression of EpCAM in the stroma of ICC is an independent risk factor for
      overall (hazard ratio = 2.6; 95% confidence interval, 1.3-5.1; P = 0.005) and
      disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2-4.2; P =
      0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue
      is closely correlated with a worst disease-free survival (P = 0.035).
      CONCLUSIONS: Our findings provide new arguments for a potential role of CSC on
      ICC progression supporting the idea that targeting CSC biomarkers might represent
      a promise personalized treatment.

PMID- 24909872
TI  - Reply to: photoreceptor layer thinning in Parkinsonian syndromes.

PMID- 24909873
TI  - A methodological review of recent meta-analyses has found significant
      heterogeneity in age between randomized groups.
AB  - BACKGROUND: There is evidence to suggest that component randomized controlled
      trials (RCTs) within systematic reviews may be biased. It is important that these
      reviews are identified to prevent erroneous conclusions influencing health care
      policies and decisions. PURPOSE: To assess the likelihood of bias in trials in 12
      meta-analyses. DESIGN: A review of 12 systematic reviews. DATA SOURCES: Twelve
      recently published systematic reviews with 503 component randomized trials,
      published in the British Medical Journal, The Lancet, Journal of the American
      Medical Association, and The Annals of Internal Medicine before May 2012. STUDY
      SELECTION AND DATA EXTRACTION: Systematic reviews were eligible for inclusion if
      they included only RCTs. We obtained the full text for the component RCTs of the
      12 systematic reviews (in English only). We extracted summary data on age, number
      of participants in each treatment group, and the method of allocation concealment
      for each RCT. DATA SYNTHESIS: Five of the 12 meta-analyses exhibited
      heterogeneity in age differences (I(2) > 0.30), when there should have been none.
      In two meta-analyses, the age of the intervention group was significantly greater
      than that of the control group. Inadequate allocation concealment was a
      statistically significant predictor of heterogeneity in one trial as observed by
      a metaregression. CONCLUSIONS: Most of the sample of recent meta-analyses showed
      that there were signs of imbalance and/or heterogeneity in ages between treatment
      groups, when there should have been none. Systematic reviewers might consider
      using the techniques described here to assess the validity of their findings.

PMID- 24909874
TI  - Biomarker identification and pathway analysis by serum metabolomics of childhood
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is a common hematological
      malignant neoplasm that typically affects children. Although intense
      chemotherapeutic regimens have been useful to combat the disease, approximately
      20% of patients will relapse despite treatment. Diagnosing ALL requires bone
      marrow puncture procedure, which many parents do not consent to for it is
      invasive. Additionally, metabolic alterations associated with the disease are
      unclear. METHODS: Metabolic alterations associated with ALL were investigated by
      performing serum metabolomics based on ultra-performance liquid chromatography
      coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate
      statistical analysis. Ingenuity Pathways Analysis (IPA) was also performed.
      RESULTS: Thirty metabolites (17 detected in positive mode and 13 in negative
      mode) were differentially expressed between patients with ALL and control
      patients; these metabolites were selected as potential biomarkers. Based on IPA
      analysis, glycerophospholipid metabolism is deregulated in patients with ALL and
      may represent an underlying metabolic pathway associated with disease
      progression. CONCLUSIONS: Metabolomics can be used to analyze the metabolic
      activity of ALL patients compared to healthy controls. The data we provide here
      suggest that glycerophospholipid metabolism may be a key mechanism underlying
      disease progression and development.

PMID- 24909875
TI  - NMR-based metabolomic urinalysis: a rapid screening test for urinary tract
      infection.
AB  - BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial
      infections in humans; however, there is no accurate and fast quantitative test to
      detect UTI. Dipstick urinalysis is semi-quantitative with a limited diagnostic
      accuracy, while urine culture is accurate but takes time. We described a
      quantitative biochemical method for the diagnosis of bacteriuria using a single
      marker. METHODS: We compared the urine metabolomes from 88 patients with
      bacterial UTI and 61 controls using (1)H NMR spectroscopy followed by principal
      component analysis (PCA) and orthogonal partial least squares-discriminant
      analysis (OPLS-DA). The biomarker identified was subsequently validated using
      independent samples. RESULTS: The urine acetic acid/creatinine (mmol/mmol) level
      was determined to be the most discriminatory marker for bacterial UTI with an
      area-under-receiver operating characteristic curve=0.97, sensitivity=91% and
      specificity=95% at the optimal cutoff 0.03 mmol/mmol. For validation, 60 samples
      were recruited prospectively. Using the optimal cutoff for acetic
      acid/creatinine, this method showed sensitivity=96%, specificity=94%, positive
      predictive value=92%, negative predictive value=97% and an overall accuracy=95%.
      The diagnostic performance was superior to dipstick urinalysis or microscopy. In
      addition, we also observed an increase of urinary trimethylamine (TMA) in
      patients with Escherichia coli-associated UTI. TMA is a mammalian-microbial co
      metabolite and the high level of TMA generated is related to the bacterial
      enzyme, trimethylamine N-oxide (TMAO) reductase which reduces TMAO to TMA.
      CONCLUSIONS: Urine acetic acid is a neglected metabolite that can be used for
      rapid diagnosis of UTI and TMA can be used for etiologic diagnosis of UTI. With
      the introduction of NMR-based clinical analyzers to clinical laboratories, NMR
      based urinalysis can be translated for clinical use.

PMID- 24909876
TI  - Preeclampsia: integrated network model of platelet biomarkers interaction as a
      tool to evaluate the hemostatic/immunological interface.
AB  - BACKGROUND: Preeclampsia (PE) is associated with platelet activation, which may
      be involved in its pathogenesis promoting coagulation and mediating inflammation.
      We investigated whether the platelet activation status together with the
      frequency of platelet-leukocyte aggregates/PLA and monocyte tissue factor/TF
      expression could be used as laboratorial biomarkers for PE diagnosis and
      prognosis. METHODS: Ninety-seven women were evaluated including severe PE/sPE
      (N=15), mild PE/mPE (N=20), normotensive pregnant/NP (N=31) and non-pregnant
      women/nonP (N=31). Platelet markers were analyzed by flow cytometry. RESULTS:
      Platelet counts and CD41a expression by platelets were lower in NP and sPE vs
      nonP. The expression of CD61 was lower during pregnancy. Altered balance of
      platelet marker expression was also observed in NP and sPE vs nonP. No
      significant differences in the PLA and TF expression by monocytes were observed
      among the groups. There are several correlations between platelet activation
      markers, especially in sPE, which suggest a relevant role of the
      hemostatic/immunological cross-talk in this disease. CONCLUSIONS: PE is not
      associated with increased platelet activation markers. It cannot rule out a role
      of platelet activation in the PE pathophysiology. Despite those correlations, we
      did not find a putative laboratorial biomarker that could be useful by itself for
      PE diagnosis and prognosis.

PMID- 24909877
TI  - High-throughput tandem mass spectrometry multiplex analysis for newborn urinary
      screening of creatine synthesis and transport disorders, Triple H syndrome and
      OTC deficiency.
AB  - BACKGROUND: Creatine synthesis and transport disorders, Triple H syndrome and
      ornithine transcarbamylase deficiency are treatable inborn errors of metabolism.
      Early screening of patients was found to be beneficial. Mass spectrometry
      analysis of specific urinary biomarkers might lead to early detection and
      treatment in the neonatal period. We developed a high-throughput mass
      spectrometry methodology applicable to newborn screening using dried urine on
      filter paper for these aforementioned diseases. METHODS: A high-throughput
      methodology was devised for the simultaneous analysis of creatine,
      guanidineacetic acid, orotic acid, uracil, creatinine and respective internal
      standards, using both positive and negative electrospray ionization modes,
      depending on the compound. RESULTS: The precision and accuracy varied by <15%.
      Stability during storage at different temperatures was confirmed for three weeks.
      The limits of detection and quantification for each biomarker varied from 0.3 to
      6.3 MUmol/l and from 1.0 to 20.9 MUmol/l, respectively. Analyses of urine
      specimens from affected patients revealed abnormal results. Targeted biomarkers
      in urine were detected in the first weeks of life. CONCLUSIONS: This rapid,
      simple and robust liquid chromatography/tandem mass spectrometry methodology is
      an efficient tool applicable to urine screening for inherited disorders by
      biochemical laboratories.

PMID- 24909878
TI  - Successful use of continuous ambulatory peritoneal dialysis in 2 adults with a
      gastrostomy.

PMID- 24909879
TI  - In vivo structure-activity relationship studies support allosteric targeting of a
      dual specificity phosphatase.
AB  - Dual specificity phosphatase 6 (DUSP6) functions as a feedback attenuator of
      fibroblast growth factor signaling during development. In vitro high throughput
      chemical screening attempts to discover DUSP6 inhibitors have yielded limited
      success. However, in vivo whole-organism screens of zebrafish identified compound
      1 (BCI) as an allosteric inhibitor of DUSP6. Here we designed and synthesized a
      panel of analogues to define the structure-activity relationship (SAR) of DUSP6
      inhibition. In vivo high-content analysis in transgenic zebrafish, coupled with
      cell-based chemical complementation assays, identified structural features of the
      pharmacophore of 1 that were essential for biological activity. In vitro assays
      of DUSP hyperactivation corroborated the results from in vivo and cellular SAR.
      The results reinforce the notion that DUSPs are druggable through allosteric
      mechanisms and illustrate the utility of zebrafish as a model organism for in
      vivo SAR analyses. 

PMID- 24909881
TI  - Exploratory factor analysis of the Oral Health Impact Profile.
AB  - Although oral health-related quality of life (OHRQoL) as measured by the Oral
      Health Impact Profile (OHIP) is thought to be multidimensional, the nature of
      these dimensions is not known. The aim of this report was to explore the
      dimensionality of the OHIP using the Dimensions of OHRQoL (DOQ) Project, an
      international study of general population subjects and prosthodontic patients.
      Using the project's Learning Sample (n = 5173), we conducted an exploratory
      factor analysis on the 46 OHIP items not specifically referring to dentures for
      5146 subjects with sufficiently complete data. The first eigenvalue (27.0) of the
      polychoric correlation matrix was more than ten times larger than the second
      eigenvalue (2.6), suggesting the presence of a dominant, higher-order general
      factor. Follow-up analyses with Horn's parallel analysis revealed a viable second
      order, four-factor solution. An oblique rotation of this solution revealed four
      highly correlated factors that we named Oral Function, Oro-facial Pain, Oro
      facial Appearance and Psychosocial Impact. These four dimensions and the strong
      general factor are two viable hypotheses for the factor structure of the OHIP.

PMID- 24909882
TI  - Evaluation of osteotomy accuracy and rotational and angular alignment for cranial
      closing wedge ostectomy performed with and without alignment aids.
AB  - OBJECTIVE: To (1) investigate the use of K-wires as alignment aids for cranial
      closing wedge ostectomy (CCWO) and (2) evaluate their effect on osteotomy
      accuracy and angular/rotational alignment. STUDY DESIGN: Cadaveric study.
      ANIMALS: Cadaveric pelvic limbs (n = 20). METHODS: CCWO was performed with and
      without alignment aids on 20 cadaveric pelvic limbs. CT scans were performed pre-
      and post-operatively to evaluate tibial torsion and valgus/varus deformity.
      Digital photographs of the ostectomized bone wedges were used to assess
      divergence of the 2 osteotomies, and the area of the medial and lateral aspects
      measured to assess osteotomy angulation within the dorsal plane. RESULTS:
      Osteotomy divergence angle, the difference between the area of the medial and
      lateral aspects of the ostectomized wedges, and the difference between the pre-
      and post-operative angles of valgus/varus deformity were all significantly
      smaller for the alignment aid group. The difference in pre- and post-operative
      tibial torsion was not significantly different between groups. CONCLUSIONS: K
      wires can be used successfully as alignment aids during CCWO and help to create a
      significantly more orthogonal osteotomy. This allows a significant reduction in
      the difference between the preoperative and postoperative angles of valgus or
      varus, which may reduce the risk of developing a clinically important
      iatrogenically introduced valgus/varus deformity postoperatively.

PMID- 24909884
TI  - Future treatments of cirrhosis.
AB  - Cirrhosis can be sub-classified in clinical stages with distinct differences in
      prognosis and can even be reversed in some cases with successful etiological
      treatment. In this article, we review potential future therapies of cirrhosis,
      mainly focusing in the expansion of indications of currently licensed drugs. We
      strongly advocate that future therapies should focus on preventing the advent of
      complications and further progression of liver disease and should involve both
      primary and secondary care physicians. Such strategies could be based on the
      combination of currently licensed, relatively safe and inexpensive drugs and such
      randomized controlled trials should be prioritized in patients with advanced
      liver disease. The paradigm should be similar to that of prevention in
      cardiovascular diseases and long-term follow-up trials are needed. 

PMID- 24909885
TI  - Lack of association between Flavobacterium columnare genomovar and virulence in
      hybrid tilapia Oreochromis niloticus (L.)*Oreochromis aureus (Steindachner).
AB  - Columnaris disease can be problematic in tilapia (Oreochromis spp.) production.
      An understanding of the pathogenesis and virulence of Flavobacterium columnare is
      needed to develop prevention strategies. The objective of this study was to
      determine the virulence of genetically defined isolates of F. columnare in sex
      reversed hybrid tilapia, Oreochromis niloticus (L.)*O. aureus (Steindachner). A
      series of immersion challenge trials were performed using isolates of the five
      established genomovars of F. columnare: I, II, II-B, III and I/II. The mean per
      cent mortality of fish challenged with genomovar I, II and III isolates ranged
      from 0 to 100, 3.3-78 and 3.3-75%, respectively. The mean per cent mortality of
      fish challenged with genomovar II-B ranged from 35 to 96.7%, and the only
      genomovar I/II isolate tested caused no mortality. Contrary to previous work in
      other fish species, there did not appear to be an association between F.
      columnare genomovar and virulence in tilapia. The challenge model used resulted
      in acute mortality. An alternative challenge model was tested by cohabitating
      healthy fish with dead fish infected with F. columnare. This method resulted in
      rapid appearance of clinical signs and mortality, suggesting the potential for F.
      columnare to increase in virulence upon growth on/in a fish host.

PMID- 24909883
TI  - The symphonic structure of childhood stress reactivity: patterns of sympathetic,
      parasympathetic, and adrenocortical responses to psychological challenge.
AB  - Despite widespread recognition that the physiological systems underlying stress
      reactivity are well coordinated at a neurobiological level, surprisingly little
      empirical attention has been given to delineating precisely how the systems
      actually interact with one another when confronted with stress. We examined cross
      system response proclivities in anticipation of and following standardized
      laboratory challenges in 664 4- to 14-year-olds from four independent studies. In
      each study, measures of stress reactivity within both the locus coeruleus
      norepinephrine system (i.e., the sympathetic and parasympathetic branches of the
      autonomic nervous system) and the corticotrophin releasing hormone system (i.e.,
      the hypothalamic-pituitary-adrenal axis) were collected. Latent profile analyses
      revealed six distinctive patterns that recurred across the samples: moderate
      reactivity (average cross-system activation; 52%-80% of children across samples),
      parasympathetic-specific reactivity (2%-36%), anticipatory arousal (4%-9%),
      multisystem reactivity (7%-14%), hypothalamic-pituitary-adrenal axis specific
      reactivity (6%-7%), and underarousal (0%-2%). Groups meaningfully differed in
      socioeconomic status, family adversity, and age. Results highlight the sample
      level reliability of children's neuroendocrine responses to stress and suggest
      important cross-system regularities that are linked to development and prior
      experiences and may have implications for subsequent physical and mental
      morbidity. 

PMID- 24909886
TI  - Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory
      skin conditions.
AB  - Environmental stimuli are known to contribute to psoriasis pathogenesis and that
      of other autoimmune diseases, but the mechanisms are largely unknown. Here we
      show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses
      environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands
      reduced inflammation in the lesional skin of psoriasis patients, whereas AhR
      antagonists increased inflammation. Similarly, AhR signaling via the endogenous
      ligand FICZ reduced the inflammatory response in the imiquimod-induced model of
      skin inflammation and AhR-deficient mice exhibited a substantial exacerbation of
      the disease, compared to AhR-sufficient controls. Nonhematopoietic cells, in
      particular keratinocytes, were responsible for this hyperinflammatory response,
      which involved upregulation of AP-1 family members of transcription factors.
      Thus, our data suggest a critical role for AhR in the regulation of inflammatory
      responses and open the possibility for novel therapeutic strategies in chronic
      inflammatory disorders. 

PMID- 24909887
TI  - Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity.
AB  - Despite development of new antiviral drugs, viral infections are still a major
      health problem. The most potent antiviral defense mechanism is the innate
      production of type I interferon (IFN-I), which not only limits virus replication
      but also promotes antiviral T cell immunity through mechanisms, which remain
      insufficiently studied. Using the murine lymphocytic choriomeningitis virus model
      system, we show here that IFN-I signaling on T cells prevented their rapid
      elimination in vivo. Microarray analyses uncovered that IFN-I triggered the
      expression of selected inhibitory NK-cell-receptor ligands. Consequently, T cell
      immunity of IFN-I receptor (IFNAR)-deficient T cells could be restored by NK cell
      depletion or in NK-cell-deficient hosts (Nfil3(-/-)). The elimination of Ifnar1(
      /-) T cells was dependent on NK-cell-mediated perforin expression. In summary, we
      identified IFN-I as a key player regulating the protection of T cells against
      regulatory NK cell function. 

PMID- 24909889
TI  - Type I interferons protect T cells against NK cell attack mediated by the
      activating receptor NCR1.
AB  - Direct type I interferon (IFN) signaling on T cells is necessary for the proper
      expansion, differentiation, and survival of responding T cells following
      infection with viruses prominently inducing type I IFN. The reasons for the
      abortive response of T cells lacking the type I IFN receptor (Ifnar1(-/-)) remain
      unclear. We report here that Ifnar1(-/-) T cells were highly susceptible to
      natural killer (NK) cell-mediated killing in a perforin-dependent manner.
      Depletion of NK cells prior to lymphocytic choriomeningitis virus (LCMV)
      infection completely restored the early expansion of Ifnar1(-/-) T cells. Ifnar1(
      /-) T cells had elevated expression of natural cytotoxicity triggering receptor 1
      (NCR1) ligands upon infection, rendering them targets for NCR1 mediated NK cell
      attack. Thus, direct sensing of type I IFNs by T cells protects them from NK cell
      killing by regulating the expression of NCR1 ligands, thereby revealing a
      mechanism by which T cells can evade the potent cytotoxic activity of NK cells. 

PMID- 24909888
TI  - Activated T cells secrete an alternatively spliced form of common gamma-chain
      that inhibits cytokine signaling and exacerbates inflammation.
AB  - The common gamma-chain (gammac) plays a central role in signaling by IL-2 and
      other gammac-dependent cytokines. Here we report that activated T cells produce
      an alternatively spliced form of gammac mRNA that results in protein expression
      and secretion of the gammac extracellular domain. The soluble form of gammac
      (sgammac) is present in serum and directly binds to IL-2Rbeta and IL-7Ralpha
      proteins on T cells to inhibit cytokine signaling and promote inflammation.
      sgammac suppressed IL-7 signaling to impair naive T cell survival during
      homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2
      signaling upon T cell activation. Reciprocally, the severity of Th17-cell
      mediated inflammatory diseases was markedly diminished in mice lacking sgammac.
      Thus, sgammac expression is a naturally occurring immunomodulator that regulates
      gammac cytokine signaling and controls T cell activation and differentiation. 

PMID- 24909890
TI  - Diagnostic utility of unenhanced computed tomography for acute aortic syndrome.
AB  - BACKGROUND: The diagnostic value of unenhanced computed tomography (CT) for
      diagnosing acute aortic dissection (AAD) and ruptured thoracic aortic aneurysm
      (TAA) remains unclear. METHODS AND RESULTS: We examined 219 consecutive patients
      who visited the emergency room with suspected acute aortic syndrome (AAS) because
      of chest or back pain and who underwent both unenhanced and contrast-enhanced 64
      row multi-detector CT. The unenhanced CT findings were evaluated by the
      cardiologist on duty who was blind to the findings of contrast-enhanced CT.
      Diagnosis of AAS was confirmed in 103 patients (47%, 95 AAD and 8 ruptured TAA
      patients) based on evaluation of both unenhanced and contrast-enhanced CT images,
      which was used as the reference standard for validating the diagnostic value of
      the unenhanced CT findings. Sensitivity and specificity of the findings of a high
      attenuation crescent, which represents hematoma in the aortic wall, were 61.2%
      and 99.1%, respectively. Sensitivity and specificity of linear high density in
      the aorta, which represents an intimal flap, were 59.2% and 96.6%, respectively.
      If unenhanced CT showed none of high-attenuation crescent, linear high density,
      internal displacement of intimal calcification, or TAA, the negative predictive
      value was 93.3%. CONCLUSIONS: Unenhanced CT is a good tool for ruling AAS in, but
      the false-negative rate of 6.7% is high for ruling AAS out because it has to be
      the minimum possible.

PMID- 24909891
TI  - Favorable vessel healing after nobori biolimus A9-eluting stent implantation-6-
      and 12-month follow-up by optical coherence tomography.
AB  - BACKGROUND: Nobori is a novel biolimus A9-eluting stent (BES) coated with a
      biodegradable polymer only on the abluminal side, which degrades over 6-9 months
      post-stent deployment. The course of vessel reaction after deployment at these
      time points remains unclear. METHODS AND RESULTS: We serially evaluated 28 BES
      implanted in de novo coronary lesions of 23 patients using optical coherence
      tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the
      percentage of stent with peri-strut low-intensity area (PLIA, a region around
      stent struts homogenously showing lesser intensity than the surrounding tissue,
      suggesting fibrin deposition or impaired neointima maturation) and that with in
      stent thrombi were evaluated. There was a significant, but small increase in
      neointimal thickness (72 +/- 23 to 82 +/- 25 um, P=0.006) from the 6- to the 12
      month follow-up, without a significant decrease in minimum lumen area (P=0.30).
      The incidences of uncovered and malapposed struts were low at 6 months and
      reduced further at 12 months (3.96 +/- 3.97% to 1.51 +/- 1.63%, P=0.001, and 0.50
      +/- 1.84% to 0.06 +/- 0.24%, P=0.20, respectively). The frequency of stent with
      PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent
      thrombi also numerically decreased (7% to 0%, P=0.24). CONCLUSIONS: Neointimal
      hyperplasia was persistently suppressed following BES implantation up to 12
      months. Simultaneously, favorable vessel healing was achieved at 6 months without
      a delaying adverse reaction for up to 12 months.

PMID- 24909892
TI  - Short-term exposure to high levels of air pollution as a risk factor for acute
      isolated pulmonary embolism.
AB  - BACKGROUND: The association between air pollution exposure and occurrence of
      venous thromboembolism is a matter of debate. This retrospective case-control
      study investigated the associations between one month's exposure to elevated
      levels of different pollutants (i.e. PM10, CO, NOx, O3, SO2, Benzene,
      Benzoapyrene, Nickel, Lead Arsenic) and the development of acute isolated
      pulmonary embolism (PE). METHODS: The cases included 33 patients consecutively
      admitted to Padua Hospital with an objectively proven diagnosis of acute
      unprovoked (i.e. without predisposing conditions) isolated (i.e. without deep
      vein thrombosis) PE. The control group consisted of 72 consecutive patients with
      objectively proven acute provoked (i.e. associated to predisposing conditions)
      isolated PE. Average mean concentrations of pollutants in the month before PE
      diagnosis were computed by monitors located at 2 different sites throughout the
      city of Padua, and were obtained from the Regional Agency for Environmental
      Protection. RESULTS: Individuals who had PM10, NOx, Benzene, Benzoapyrene,
      Cadmium, and Lead exposure equal/above the 2nd tertile, measured in controls,
      showed a significant increase in the risk of unprovoked PE. In case of PM10 and
      Benzoapyrene this risk was not affected after adjustment for possible
      confounders. In fact, in the multivariate logistic regression analysis, the OR
      values were 5.24 (95% CI: 1.52-18.12) for PM10 and 3.95 (95% CI: 1.06-14.71) for
      Benzoapyrene exposure in the month before PE diagnosis. CONCLUSIONS: Our results,
      although preliminary, identify short-term (i.e. one month) exposure to elevate
      levels of air pollutants as a possible risk factor for the development of acute
      isolated PE. Larger studies are needed to confirm our results.

PMID- 24909893
TI  - Asking questions of a palliative care nurse practitioner on a pancreatic cancer
      website.
AB  - OBJECTIVE: Increasing evidence demonstrates the benefits of online cancer
      interventions but very little about the needs of those with pancreatic cancer or
      interaction with online providers. Our study was done to (1) see how many people
      would visit a webpage where they could interact with a palliative care nurse
      practitioner (PCNP), (2) see how many would ask the PCNP questions, (3) determine
      the type of questions, and (4) obtain feedback regarding the usefulness of the
      webpage. METHOD: Mixed-methods descriptive design. RESULTS: There were 2174
      visits to the webpage, and a total of 84 participants sent 110
      questions/comments. Some 28 (33%) were people worried that they might have
      pancreatic cancer. Most questions (59, 53%) had to do with palliative care
      issues, with the largest subgroup (26, 23%) involving psychological concerns. A
      total of 39 completed an online survey and were relatives (20, 52%), or patients
      (17, 44%). They rated the webpage at 3.3/4 as being helpful at learning about the
      physical symptoms/treatments of pancreatic cancer, at 3.1/4 for learning about
      emotional issues, at 3/4 for learning about palliative care, at 2.8/4 for
      learning about hospice, and at 3.3/4 for reading other people's questions.
      SIGNIFICANCE OF RESULTS: The PCNP webpage was a helpful resource. Most asking
      questions were worried about having or getting pancreatic cancer. More research
      is needed into online providers, interventions, and conducting research online.

PMID- 24909894
TI  - Natural infection of human adenovirus 36 in rhesus monkeys is associated with a
      reduction in fasting glucose 36.

PMID- 24909895
TI  - Nativity status and sources of care assistance among elderly Mexican-origin
      adults.
AB  - Much like other racial/ethnic groups, Latinos are facing challenges to provide
      needed care to aging adults. Older Latinos underutilize nursing homes and home
      health care services and primarily rely on their families for assistance. While
      this general trend has been established, little attention has been paid to
      nativity differentials in patterns of caregiving for this segment of the aging
      population. The analyses are based on the latest wave (Wave 7) of the Hispanic
      Established Population for Epidemiologic Studies of the Elderly or H-EPESE
      (2010/2011) a sample of older Mexican-origin adults and their family caregivers
      living in the southwestern U.S. We examine 629 child caregiver/parent care
      recipient dyads using bivariate statistics and multinomial logistic regression
      analyses. The results reveal that while grown children of Mexican-origin elders
      play a critical role in providing instrumental and financial supports to their
      aging parents, the burden that the children of foreign-born parents bear is
      greater. Despite higher rates of disability, Mexican-born elders are more
      dependent on a child for help and far less likely to call upon other family
      members, relatives and community based-providers for help than the U.S. born.
      Given the recent and future growth of older Latinos, intervention strategies will
      need to focus on nativity status and acculturative processes in the context of
      caregiving and caregiver burden. 

PMID- 24909897
TI  - Corticofugal projections from medial primary somatosensory cortex avoid EphA7
      expressing neurons in striatum and thalamus.
AB  - Within the first two postnatal weeks, corticostriatal axons from the primary
      somatosensory cortex (S1) form topographic projections that organize into
      characteristic bands of axon terminals in the dorsolateral striatum. Molecules
      regulating the development of these topographically organized projections are
      currently unknown. Thus, the present study investigated whether EphA receptor
      tyrosine kinases, which regulate axonal guidance in the visual system via axon
      repulsion, could participate in the formation of corticostriatal connections
      during development. Prior studies indicate that EphA7-expressing striatal neurons
      are organized into banded compartments resembling the matrisome innervation
      pattern formed by cortical afferents from the S1 cortex and that ephrin-A5, a
      known EphA7 ligand, is expressed in a medial (high) to lateral (low) gradient in
      S1. Thus, we hypothesized that the organization of EphA7-expressing striatal
      neurons in banded domains provides a repulsive barrier preventing corticostriatal
      axons containing EphA7-ligands from innervating inappropriate regions of the
      striatum. To evaluate this, we injected the anterograde tracer, biotinylated
      dextran amine (BDA), into two locations in medial areas of S1 (the anterior and
      posterior whisker fields), which are reported to express high levels of ephrin-A5
      during development. Injections were made in mouse pups on postnatal day 9 (P9)
      and the animals were processed for immunohistochemistry on P12. Our data
      demonstrate that projections from both the forelimb/anterior whisker field and
      the posterior whisker field avoid EphA7-expressing neurons and terminate in a
      banded pattern in regions with very low EphA7-expression. We also determined that
      corticothalamic projections from medial S1 also exhibit a restricted distribution
      in the thalamus and avoid neurons expressing EphA7. Thus, our results support the
      hypothesis that the anatomical organization of striatal and thalamic neurons
      expressing EphA7 receptors restricts the topographic distribution of cortical
      afferents from medial regions of S1 which express high levels of ephrin-A5. 

PMID- 24909896
TI  - Relationships between androgens, serotonin gene expression and innervation in
      male macaques.
AB  - Androgen administration to castrated individuals was purported to decrease
      activity in the serotonin system. However, we found that androgen administration
      to castrated male macaques increased fenfluramine-induced serotonin release as
      reflected by increased prolactin secretion. In this study, we sought to define
      the effects of androgens and aromatase inhibition on serotonin-related gene
      expression in the dorsal raphe, as well as serotonergic innervation of the LC.
      Male Japanese macaques (Macaca fuscata) were castrated for 5-7 months and then
      treated for 3 months with (1) placebo, (2) testosterone (T), (3)
      dihydrotestosterone (DHT; non-aromatizable androgen) and ATD (steroidal aromatase
      inhibitor), or (4) Flutamide (FLUT; androgen antagonist) and ATD (n=5/group).
      This study reports the expression of serotonin-related genes: tryptophan
      hydroxylase 2 (TPH2), serotonin reuptake transporter (SERT) and the serotonin 1A
      autoreceptor (5HT1A) using digoxigenin-ISH and image analysis. To examine the
      production of serotonin and the serotonergic innervation of a target area
      underlying arousal and vigilance, we measured the serotonin axon density entering
      the LC with ICC and image analysis. TPH2 and SERT expression were significantly
      elevated in T- and DHT + ATD-treated groups over placebo- and FLUT + ATD-treated
      groups in the dorsal raphe (p < 0.007). There was no difference in 5HT1A
      expression between the groups. There was a significant decrease in the pixel area
      of serotonin axons and in the number of varicosities in the LC across the
      treatment groups with T > placebo > DHT + ATD = FLUT + ATD treatments.
      Comparatively, T- and DHT + ATD-treated groups had elevated TPH2 and SERT gene
      expression, but the DHT + ATD group had markedly suppressed serotonin axon
      density relative to the T-treated group. Further comparison with previously
      published data indicated that TPH2 and SERT expression reflected yawning and
      basal prolactin secretion. The serotonin axon density in the LC agreed with the
      area under the fenfluramine-stimulated prolactin curve, providing a morphological
      basis for the pharmacological results. This suggested that androgen activity
      increased TPH2 and SERT gene expression but, aromatase activity, and neural
      production of estradiol (E), may subserve axonal serotonin and determination of
      the compartment acted upon by fenfluramine. In summary, androgens stimulated
      serotonin-related gene expression, but aromatase inhibition dissociated gene
      expression from the serotonin innervation of the LC terminal field and
      fenfluramine-stimulated prolactin secretion.

PMID- 24909899
TI  - NREM sleep hypersomnia and reduced sleep/wake continuity in a neuroendocrine
      mouse model of anxiety/depression based on chronic corticosterone administration.
AB  - Sleep/wake disorders are frequently associated with anxiety and depression and to
      elevated levels of cortisol. Even though these alterations are increasingly
      sought in animal models, no study has investigated the specific effects of
      chronic corticosterone (CORT) administration on sleep. We characterized
      sleep/wake disorders in a neuroendocrine mouse model of anxiety/depression, based
      on chronic CORT administration in the drinking water (35 MUg/ml for 4 weeks,
      "CORT model"). The CORT model was markedly affected during the dark phase by non
      rapid eye movement sleep (NREM) increase without consistent alteration of rapid
      eye movement (REM) sleep. Total sleep duration (SD) and sleep efficiency (SE)
      increased concomitantly during both the 24h and the dark phase, due to the
      increase in the number of NREM sleep episodes without a change in their mean
      duration. Conversely, the total duration of wake decreased due to a decrease in
      the mean duration of wake episodes despite an increase in their number. These
      results reflect hypersomnia by intrusion of NREM sleep during the active period
      as well as a decrease in sleep/wake continuity. In addition, NREM sleep was
      lighter, with an increased electroencephalogram (EEG) theta activity. With regard
      to REM sleep, the number and the duration of episodes decreased, specifically
      during the first part of the light period. REM and NREM sleep changes correlated
      respectively with the anxiety and the anxiety/depressive-like phenotypes,
      supporting the notion that studying sleep could be of predictive value for
      altered emotional behavior. The chronic CORT model in mice that displays hallmark
      characteristics of anxiety and depression provides an insight into understanding
      the changes in overall sleep architecture that occur under pathological
      conditions.

PMID- 24909900
TI  - Evidence of bidirectional flow in the sciatic vasa nervorum.
AB  - The purpose of this study was to determine whether bidirectional flow exists in
      the sciatic vasa nervorum. Images obtained using high-frequency color Doppler
      ultrasound in duplex imaging mode (Vevo 2100) were studied retroactively. In Fig.
      1 (left panel; rat 1), the color Doppler signal and flow-velocity waveforms are
      indicative of pulsatile flow traveling towards (B) and away (C) from the probe.
      In the right panel (Fig. 1; rat 2), there appears to be three distinct vessels,
      reflective of non-pulsatile negative flow (D), and pulsatile positive (E) and
      negative (F) flows. These data confirm the presence of bidirectional arterial
      flow in the sciatic vasa nervorum. Investigating bidirectional flow in the intact
      whole nerve may be helpful in elucidating novel features of nerve blood flow
      control in healthy and diseased states. 

PMID- 24909898
TI  - Metabotropic glutamate receptors in auditory processing.
AB  - As the major excitatory neurotransmitter used in the vertebrate brain, glutamate
      activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate
      fast and slow neuronal actions, respectively. Important modulatory roles of
      mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been
      developed for the treatment of brain disorders. Here, I review studies on mGluRs
      in the auditory system. Anatomical expression of mGluRs in the cochlear nucleus
      has been well characterized, while data for other auditory nuclei await more
      systematic investigations at both the light and electron microscopy levels. The
      physiology of mGluRs has been extensively studied using in vitro brain slice
      preparations, with a focus on the lower auditory brainstem in both mammals and
      birds. These in vitro physiological studies have revealed that mGluRs participate
      in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and
      maintain the balance between excitation and inhibition in a variety of auditory
      structures. However, very few in vivo physiological studies on mGluRs in auditory
      processing have been undertaken at the systems level. Many questions regarding
      the essential roles of mGluRs in auditory processing still remain unanswered and
      more rigorous basic research is warranted. 

PMID- 24909901
TI  - Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper
      homeostasis.
AB  - Copper is an essential yet toxic metal and its overload causes Wilson disease, a
      disorder due to mutations in copper transporter ATP7B. To remove excess copper
      into the bile, ATP7B traffics toward canalicular area of hepatocytes. However,
      the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in
      response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports
      metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the
      interaction with p62 subunit of dynactin that allows lysosome translocation
      toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis
      stimulates copper clearance from the hepatocytes and rescues the most frequent
      Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our
      findings indicate that lysosomes serve as an important intermediate in ATP7B
      trafficking, whereas lysosomal exocytosis operates as an integral process in
      copper excretion and hence can be targeted for therapeutic approaches to combat
      Wilson disease. 

PMID- 24909904
TI  - Celecoxib attenuates hepatic cirrhosis through inhibition of epithelial-to
      mesenchymal transition of hepatocytes.
AB  - BACKGROUND AND AIM: The epithelial-mesenchymal transition (EMT) of hepatocytes is
      a key step for hepatic fibrosis and cirrhosis. Long-term administration of
      celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, can ameliorate hepatic
      fibrosis. This research aimed to examine the effect of celecoxib on the EMT of
      hepatocytes during the development of liver cirrhosis. METHODS: Cirrhotic liver
      model of rat was established by peritoneal injection of thiacetamide (TAA).
      Thirty-six rats were randomly assigned to control, TAA, and TAA + celecoxib
      groups. Hepatic expressions of tumor necrosis factor-alpha (TNF-alpha),
      interleukin 6 (IL-6), COX-2, prostaglandin E2 (PGE2 ), matrix metalloproteinase
      (MMP)-2 and -9, transforming growth factor-beta1 (TGF-beta1), Phospho-Smad2/3,
      Snail1, alpha-smooth muscle actin (alpha-SMA), vimentin, collagen I, fibroblast
      specific protein (FSP-1), E-cadherin and N-cadherin were quantitated. Hepatic
      fibrosis was assessed by the visible hepatic fibrotic areas and Ishak's scoring
      system. RESULTS: Exposed to TAA treatment, hepatocytes underwent the process of
      EMT during hepatic fibrosis. Compared with those in TAA group, celecoxib
      significantly downregulated the hepatic expressions of TNF-alpha, IL-6, COX-2,
      PGE2 , MMP-2, MMP-9, TGF-beta1, Phospho-Smad2/3, Snail1, alpha-SMA, FSP-1, and
      vimentin while greatly restoring the levels of E-cadherin. The fibrotic areas and
      collagen I levels of TAA + celecoxib group were much lower than those in TAA
      group. CONCLUSIONS: Celecoxib could ameliorate hepatic fibrosis and cirrhosis in
      TAA-rat model through suppression of the mesenchymal biomarkers in the
      hepatocytes while restoring the levels of their epithelial biomarkers. The
      inhibitory effect of celecoxib on the EMT of hepatocytes is associated with
      reduction of intrahepatic inflammation, preservation of normal basement matrix,
      and inhibition of TGF-beta1/Smad pathway.

PMID- 24909903
TI  - Evidence for a glassy state in strongly driven carbon.
AB  - Here, we report results of an experiment creating a transient, highly correlated
      carbon state using a combination of optical and x-ray lasers. Scattered x-rays
      reveal a highly ordered state with an electrostatic energy significantly
      exceeding the thermal energy of the ions. Strong Coulomb forces are predicted to
      induce nucleation into a crystalline ion structure within a few picoseconds.
      However, we observe no evidence of such phase transition after several tens of
      picoseconds but strong indications for an over-correlated fluid state. The
      experiment suggests a much slower nucleation and points to an intermediate glassy
      state where the ions are frozen close to their original positions in the fluid. 

PMID- 24909902
TI  - Homeotic function of Drosophila Bithorax-complex miRNAs mediates fertility by
      restricting multiple Hox genes and TALE cofactors in the CNS.
AB  - The Drosophila Bithorax complex (BX-C) Hox cluster contains a bidirectionally
      transcribed miRNA locus, and a deletion mutant (Deltamir) lays no eggs and is
      completely sterile. We show these miRNAs are expressed and active in distinct
      spatial registers along the anterior-posterior axis in the CNS. Deltamir larvae
      derepress a network of direct homeobox gene targets in the posterior ventral
      nerve cord (VNC), including BX-C genes and their TALE cofactors. These are
      phenotypically critical targets, because sterility of Deltamir mutants was
      substantially rescued by heterozygosity of these genes. The posterior VNC
      contains Ilp7+ oviduct motoneurons, whose innervation and morphology are
      defective in Deltamir females, and substantially rescued by heterozygosity of
      Deltamir targets, especially within the BX-C. Collectively, we reveal (1)
      critical roles for Hox miRNAs that determine segment-specific expression of
      homeotic genes, which are not masked by transcriptional regulation; and (2) that
      BX-C miRNAs are essential for neural patterning and reproductive behavior.

PMID- 24909905
TI  - Increased interleukin-27 promotes Th1 differentiation in patients with chronic
      immune thrombocytopenia.
AB  - Chronic immune thrombocytopenia (cITP) is an autoimmune disease with disturbed
      cytokine profile. Although plasma levels of IL-27 are shown to be associated with
      cITP, its association with T cell subsets has not been studied. The objective of
      this study was to study the association between IL-27 and different T cell
      subsets in patients with cITP. Heparinized blood was collected from 31 patients
      with cITP and 36 healthy controls (platelet count <100 * 10(9)/l and 103-280 *
      10(9)/l, respectively). The percentage of Th1, Th2 and Th17 cells in peripheral
      blood mononuclear cells (PBMCs) were enumerated by flow cytometry, and the mRNA
      levels of IL-27, T-bet, GATA-3 and retinoid-related orphan receptor gamma
      (RORgammat) by real-time reverse transcriptase polymerase chain (RT-PCR). Plasma
      cytokine levels of IL-27, interferon-gamma (IFN-gamma), IL-4 and IL-17A were
      estimated by flow cytometrix. The effect of exogenous recombinant IL-27(rhIL-27)
      on the differentiation of T cells into Th1, Th2 and Th17 cells was investigated
      by cell culture. The percentage of Th1 and Th17 cells and the plasma
      concentration and mRNA levels of IL-27 were significantly higher in cITP patients
      compared with healthy controls. Plasma levels of IL-27 correlated positively with
      percentage of Th1 cells in patients with cITP. Exogenous (rhIL-27) could
      significantly up-regulate the percentage of Th1 cells and down-regulate Th2 cells
      in vitro. Th17 cells were reduced in the presence of (rhIL-27) in controls but
      had no effect in patients with cITP. The up-regulation of IL-27 might cause Th1
      differentiation and might be involved in the pathophysiology of cITP.

PMID- 24909906
TI  - Rapid determination of cellulose.
AB  - The cellulose analysis results of four feedstocks and Avicel obtained by a one
      step/two-step hydrolysis method were compared to the conventional cellulose assay
      according to Updegraff. Slightly lower cellulose levels were observed for Avicel
      (97%), corn stover (97%), poplar (96%), and Miscanthus (94%) but for pine the
      amounts were almost identical (101%). Despite these differences, the one-step/two
      step method can be seen as a true alternative to the more labor-intensive
      Updegraff method.

PMID- 24909908
TI  - Artificial liver.
AB  - Artificial liver generally is classified as either inert or cell-based, although
      only the latter is a true artificial liver. Despite some major achievements and
      investment, no device is currently available; devices have either not been tested
      rigorously, or have failed to meet expectations in clinical trials. A successful
      device will provide the appropriate level of liver function, but it also must be
      applied in the appropriate clinical setting. An extracorporeal device may be
      capable of supporting a failing liver, but it will not correct portal
      hypertension. The future of this field depends on both the technical aspects of
      the device(s) and their application to the appropriate clinical situation. 

PMID- 24909907
TI  - FibroScan (vibration-controlled transient elastography): where does it stand in
      the United States practice.
AB  - With widespread screening and increasingly effective treatments for patients with
      viral hepatitis as well as the increasing prevalence of nonalcoholic fatty liver
      disease, the population presenting to the care of gastroenterologists and
      hepatologists is certain to increase. Assessment of advanced liver disease is
      traditionally invasive and expensive. Vibration-controlled transient
      elastography, commonly delivered by the FibroScan device, is an option recently
      approved by the Food and Drug Administration for the noninvasive assessment of
      liver disease at the point of care. Herein, we review the promise and pitfalls of
      vibration-controlled transient elastography with the aim of providing clinicians
      with a framework to interpret its results and apply this technology to the
      changing needs of our patients. 

PMID- 24909909
TI  - Management of Hepatocellular Adenoma: Recent Advances.
AB  - Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs
      more frequently in young women with a history of prolonged use of oral
      contraceptives. Surgical resection is considered because of the risk of
      hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA
      is a heterogeneous disease comprising 3 subtypes with distinct molecular and
      complication profiles. The inflammatory or telangiectatic subtype is at increased
      risk for hemorrhage, the beta-catenin-activated subtype is at increased risk for
      malignant transformation, and the hepatocyte nuclear factor-1alpha-inactivated or
      steatotic subtype is at the least risk for complications. One-third of the
      patients with HCA have multiple tumors on imaging with no increased risk of
      complications. Magnetic resonance imaging is the modality of choice for the
      diagnosis and subtype characterization of HCA. Systematic resection of HCA is
      recommended in male patients owing to the higher incidence of malignant
      transformation, and surgical excision in women should be reserved for tumors 5 cm
      or larger associated with an increased risk of complications. Cessation of
      hormonal therapy and radiologic surveillance in women with HCA tumors smaller
      than 5 cm shows that the vast majority of HCA remain stable or undergo
      spontaneous regression. Percutaneous core needle biopsy is of limited value
      because the therapeutic strategy is based primarily on patient sex and tumor
      size. Transarterial embolization is the initial treatment for HCA complicated by
      hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however,
      frequent sonographic surveillance is recommended.

PMID- 24909910
TI  - Building the multidisciplinary team for management of patients with
      hepatocellular carcinoma.
AB  - Optimal care of the patient with hepatocellular carcinoma (HCC) necessitates the
      involvement of multiple providers. Because the patient with HCC often carries 2
      conditions with competing mortality risks (cancer and underlying cirrhosis), no
      single provider is equipped to deal with all of these patients' needs adequately.
      Multidisciplinary teams (MDTs) have evolved to facilitate care coordination,
      reassessments of clinical course, and nimble changes in treatment plans required
      for this complex group of patients. Providers or sites that elect to manage
      patients with HCC thus are increasingly aware of the need to build their own MDT
      or communicate with an established one. The availability of new communication
      technologies, such as teleconferencing or teleconsultation, offers the
      possibility of MDT expansion into underserved or rural areas, as well as areas
      such as correctional facilities. Although the availability of resources for HCC
      patient care varies from site to site, construction of an MDT is possible in a
      wide spectrum of clinical practices, and this article suggests a blueprint for
      assembly of such collaboration. Research strategies are needed to explain how
      MDTs improve clinical outcomes so that MDTs themselves can be improved. 

PMID- 24909911
TI  - Radiosensitization of pancreatic cancer cells by metformin through the AMPK
      pathway.
AB  - Pancreatic cancer is relatively radioresistant, however, radiotherapy has been
      shown to provide efficacy in the treatment of local disease. To increase the
      effectiveness of radiotherapy in pancreatic cancer, radiosensitizing drugs are
      under development. In this study, we investigated the radiosensitizing activity
      of the anti-diabetic drug metformin on pancreatic cancer cells in vitro. We
      demonstrated that metformin radiosensitized MiaPaCa-2 and Panc1 cells with
      radiation enhancement ratios (ER) ranging from 1.33-1.45 with metformin
      concentrations of 30-100 MUM, and in addition, we showed that metformin
      sensitized cells to gemcitabine alone or in combination with radiation treatment.
      In addition, we found that pancreatic cancer stem cell-like cells showed enhanced
      radiosensitization in a tumorsphere assay with a REF of 1.66. At these
      radiosensitizing doses, metformin alone had low toxicity (as shown by >75%
      clonogenic survival) and did not affect cell cycle. The combination of metformin
      and radiation yielded greater numbers of gamma-H2AX foci after 1 h compared to
      radiation alone, suggesting increased DNA damage signaling. Examination of the
      AMPK pathway showed that pharmacological inhibition of AMPK signaling or RNAi of
      AMPKalpha1 reversed metformin-mediated radiosensitization. These studies show
      that metformin radiosensitization of pancreatic cancer cells at micromolar
      concentration acts through AMPK and may affect DNA damage signaling. The data
      indicate that metformin may increase the efficacy of radiation therapy for
      pancreatic cancer. 

PMID- 24909912
TI  - Collective fluorescence switching of counterion-assembled dyes in polymer
      nanoparticles.
AB  - The current challenge in the field of fluorescent nanoparticles (NPs) for
      bioimaging is to achieve extreme brightness and external control of their
      emission using biodegradable materials. Here we propose a new concept of
      fluorescent polymer NPs, doped with ionic liquid-like salts of a cationic dye
      (octadecyl rhodamine B) with a bulky hydrophobic counterion (fluorinated
      tetraphenylborate) that serves as spacer minimizing dye aggregation and self
      quenching. The obtained 40-nm poly(D,L-lactide-co-glycolide) NPs containing up to
      500 dyes are brighter than quantum dots and exhibit photo-induced reversible
      on/off fluorescence switching, never reported for dye-doped NPs. We show that
      this collective switching of hundreds of dyes is due to ultrafast excitation
      energy transfer and can be used for super-resolution imaging. These NPs, being
      spontaneously endocytosed by living cells, feature high signal-to-noise ratio and
      absence of toxicity. The counterion-based concept opens the way to a new class of
      nanomaterials for sensing, imaging and light harvesting. 

PMID- 24909913
TI  - Immunohistochemical evaluation of vitiliginous hair follicle melanocyte
      reservoir: is it retained?
AB  - BACKGROUND: Vitiligo is an acquired depigmentaion of skin and hair. The presence
      of white hair within vitiligo lesions is considered a bad prognostic sign since
      these lesions are difficult to repigment. Melanocyte reservoir was not
      extensively studied in vitiliginous white hair. OBJECTIVE: To evaluate pigment
      cell reservoir in vitiliginous black and white hair. METHOD: Using
      immunohistochemical technique, skin biopsies from 30 vitiligo patients (including
      either black or white hair) and 10 age- and gender-matched healthy subjects were
      examined. Human Melanoma Black-45 (HMB-45) was used for detecting active
      melanocytes and Tyrosinase Related Protein 2 (TRP2) for detecting the whole
      melanocyte lineage including melanocyte stem cells (MelSC). RESULTS: About 61.1%
      of black hair was positive for HMB-45 and 83.3% was positive for TRP2. About 25%
      of white hair was positive for HMB-45 and 75% retained TRP2 positivity.
      Follicular HMB-45 expression and TRP2 expression percentage were significantly
      lower in white than black hair (P = 0.05, 0.04 respectively). Epidermal HMB-45
      and TRP2 expression percentages were significantly higher in lesions containing
      black rather than white hair (P < 0.001, P = 0.05 respectively). Black hair was
      significantly associated with histologically pigmented hair follicles (P =
      0.049), and with residual interfollicular melanin pigment (P = 0.007).
      CONCLUSION: Melanocytes, either active (melanotic) or inactive (amelanotic which
      may include MelSC), are not totally absent from vitiliginous white hair. However,
      intact melanocyte reservoir was observed more in black than white hair. This may
      add avenues for future research about the possibility of white vitiliginous hair
      to repigment.

PMID- 24909914
TI  - Interrogating the integument: the role of the epidermis in hair induction.
AB  - Hair follicle development is driven by interactions between the epithelium and
      underlying mesenchyme. These reciprocal interactions are essential for
      development, as a lack of response from either the mesenchyme or epithelium
      results in arrested growth. A large body of research has focused on the role of
      mesenchymal cells during hair follicle development and their inductive properties
      for hair neogenesis. In this commentary, the role of the epidermis during hair
      follicle induction will be discussed. 

PMID- 24909916
TI  - Population-based assessment of sensitivity and specificity of a pinhole for
      detection of significant refractive errors in the community.
AB  - BACKGROUND: Measurements of refractive errors through subjective or automated
      refraction are not always possible in rapid assessment studies and community
      vision screening programs; however, measurements of vision with habitual
      correction and with a pinhole can easily be made. Although improvements in vision
      with a pinhole are assumed to mean that a refractive error is present, no studies
      have investigated the magnitude of improvement in vision with pinhole that is
      predictive of refractive error. The aim was to measure the sensitivity and
      specificity of 'vision improvement with pinhole' in predicting the presence of
      refractive error in a community setting. METHODS: Vision and vision with pinhole
      were measured using a logMAR chart for 488 of 582 individuals aged 15 to 50
      years. Refractive errors were measured using non-cycloplegic autorefraction and
      subjective refraction. The presence of refractive error was defined using
      spherical equivalent refraction (SER) at two levels: SER greater than +/- 0.50 D
      sphere (DS) and SER greater than +/-1.00 DS. Three definitions for significant
      improvement in vision with a pinhole were used: 1. Presenting vision less than
      6/12 and improving to 6/12 or better, 2. Improvement in vision of more than one
      logMAR line and 3. Improvement in vision of more than two logMAR lines. RESULTS:
      For refractive error defined as spherical equivalent refraction greater than +/-
      0.50 DS, the sensitivities and specificities for the pinhole test predicting the
      presence of refractive error were 83.9 per cent (95% CI: 74.5 to 90.9) and 98.8
      per cent (95% CI: 97.1 to 99.6), respectively for definition 1. Definition 2 had
      a sensitivity 89.7 per cent (95% CI: 81.3 to 95.2) and specificity 88.0 per cent
      (95% CI: 4.4 to 91.0). Definition 3 had a sensitivity of 75.9 per cent (95% CI:
      65.5 to 84.4) and specificity of 97.8 per cent (95% CI: 95.8 to 99.0). Similar
      results were found with spherical equivalent refraction greater than +/-1.00 DS,
      when tested against the three pinhole-based definitions. CONCLUSION: Refractive
      error definitions based on improvement in vision with the pinhole shows good
      sensitivity and specificity at predicting the presence of significant refractive
      errors. These definitions can be used in rapid assessment surveys and community
      based vision screenings.

PMID- 24909918
TI  - Paediatric end-of-life care in the home care setting (PELICAN HOME)--a mixed
      methods study protocol.
AB  - AIMS: (a) To explore parental experiences and needs during their child's end-of
      life care at home; (b) to explore patient's characteristics and current provision
      of paediatric end-of-life care in the home care setting in Switzerland; and (c)
      to determine influencing system factors impacting end-of-life care at home.
      BACKGROUND: Parental experiences/needs and paediatric end-of-life care services
      in the home care setting are influenced by national healthcare policy,
      determinants of the family and the individual patient. In Switzerland, there is a
      lack of information about the provision of paediatric end-of-life care at home
      and related parent's experiences/needs. DESIGN: Sub-study of the nationwide
      multicenter study 'Paediatric End-of-Life CAre Needs in Switzerland' using a
      concurrent qualitative embedded mixed methods design. METHODS: Data will be
      collected from January-May 2014 through community care organizations and
      children's hospitals. The study includes approximately 40-50 families whose child
      (0-18 years) died in the years 2011-2012 due to a cardiological, neurological or
      oncological condition and spent at least 21 days at home during the last 4 weeks
      of life. Qualitative data will be collected through semi-structured interviews
      with parents and analysed by 'thematic analysis'. Quantitative data about
      patient's characteristics will be obtained from patient's medical charts and
      parental experiences/needs through the parental questionnaire. Appropriate
      descriptive and inference statistical methods will be used for data analysis.
      DISCUSSION: This study will provide comprehensive basic information about
      parental needs and patient characteristics for the provision of paediatric end-of
      life care and may promote the development of family-centred paediatric end-of
      life care services at home. STUDY REGISTRATION: The PELICAN-study is registered
      in the database of Clinical Trial gov. Study ID-number: NCT 01983852.

PMID- 24909917
TI  - KITENIN-targeting microRNA-124 suppresses colorectal cancer cell motility and
      tumorigenesis.
AB  - MicroRNAs are increasingly implicated in the modulation of the progression of
      various cancers. We previously observed that KAI1 C-terminal interacting
      tetraspanin (KITENIN) is highly expressed in sporadic human colorectal cancer
      (CRC) tissues and hence the functional KITENIN complex acts to promote
      progression of CRC. However, it remains unknown that microRNAs target KITENIN and
      whether KITENIN-targeting microRNAs modulate CRC cell motility and colorectal
      tumorigenesis. Here, through bioinformatic analyses and functional studies, we
      showed that miR-124, miR-27a, and miR-30b negatively regulate KITENIN expression
      and suppress the migration and invasion of several CRC cell lines via modulation
      of KITENIN expression. Through in vitro and in vivo induction of mature microRNAs
      using a tetracycline-inducible system, miR-124 was found to effectively inhibit
      the invasion of CT-26 colon adenocarcinoma cells and tumor growth in a syngeneic
      mouse xenograft model. Constitutive overexpression of precursor miR-124 in CT-26
      cells suppressed in vivo tumorigenicity and resulted in decreased expression of
      KITENIN as well as that of MYH9 and SOX9, which are targets of miR-124. Thus, our
      findings identify that KITENIN-targeting miR-124, miR-27a, and miR-30b function
      as endogenous inhibitors of CRC cell motility and demonstrate that miR-124 among
      KITENIN-targeting microRNAs plays a suppressor role in colorectal tumorigenesis. 

PMID- 24909919
TI  - Human papillomavirus vaccination: where are we now?
AB  - The development of efficacious prophylactic human papillomavirus vaccines
      provided an opportunity for the primary prevention of related infections and
      diseases. Certain oncogenic human papillomaviruses that preferentially infect the
      genital epithelium cause cervical cancer and a substantial proportion of anal,
      penile, vaginal, vulvar and oropharyngeal cancers. Following extensive clinical
      trials demonstrating their efficacy and safety, two vaccines have been in global
      use for over 6 years. This review summarises the accumulated evidence regarding
      their high level of efficacy, safety in population usage, reductions in genital
      warts, infections and cervical disease following their adoption, and facilitators
      and barriers to achieving high vaccination coverage. The review also discusses
      practical issues and frequently asked questions regarding duration of effect,
      vaccination of women treated for cervical disease and alternate vaccination
      schedules, as well as the need to review cervical screening strategies in the
      post- vaccination environment. 

PMID- 24909920
TI  - Association between tobacco smoking and prognosis of occupational hand eczema: a
      prospective cohort study.
AB  - BACKGROUND: Hand eczema (HE) is a common occupational skin disease. Tobacco
      smoking is known to be associated with adverse cutaneous effects. However, its
      influence on the prognosis of occupational HE has not yet been studied.
      OBJECTIVES: To evaluate relations between smoking status, severity and prognosis
      of occupational HE in patients taking part in an interdisciplinary tertiary
      individual prevention programme (TIP). METHODS: In a prospective, multicentre,
      cohort study 1608 patients with occupational HE taking part in a TIP were
      recruited and followed up for 3 years. The clinical and self-reported outcome
      data of smokers and nonsmokers were compared. RESULTS: Nonsmokers and smokers
      were equally distributed. During the TIP, the average self-reported daily
      cigarette consumption and the severity of HE decreased significantly (P < 0.01).
      However, at all time points HE was significantly more severe in smokers than in
      nonsmokers. This association was not dependent on the self-reported number of
      cigarettes smoked daily. Smokers had significantly more days of absence from work
      due to occupational HE than nonsmokers in the year before the TIP (P < 0.01) and
      in the following year (P = 0.02). After the TIP, smokers reported significantly
      more often that they had to give up their occupation (P = 0.02) than nonsmokers.
      CONCLUSIONS: The severity of occupational HE is increased in smokers. Tobacco
      smoking is associated with a higher number of days of absence from work and with
      not staying in the workforce owing to occupational HE. Thus, smoking confers a
      worse prognosis and interferes with the outcome of prevention programmes.

PMID- 24909921
TI  - Central nervous system prophylaxis in patients with diffuse large B cell
      lymphoma, are we treating ourselves? A response to the recent BCSH Guideline.

PMID- 24909923
TI  - Improving prospects for treating hypoactive sexual desire disorder (HSDD):
      development status of flibanserin.

PMID- 24909925
TI  - Characterization of the key odorants in light aroma type chinese liquor by gas
      chromatography-olfactometry, quantitative measurements, aroma recombination, and
      omission studies.
AB  - The light aroma type liquor is widely welcomed by consumers due to its pleasant
      fruity and floral aroma, particularly in northern China. To answer the puzzling
      question of which key aroma compounds are responsible for the typical aroma,
      three typical liquors were studied in this paper. A total of 66 aroma compounds
      were identified in three liquors by means of gas chromatography-olfactometry (GC
      O) coupled with mass spectrometry (MS), and 27 odorants were further screened out
      as the important odorants according to quantitative study and odor activity
      values (OAVs). For OAV calculation, odor thresholds of the odorants were
      determined in a hydroalcoholic solution at 46% ethanol by volume. The typical
      light type aroma dominated by fruity and floral notes was successfully simulated
      by dissolving these important odorants in the 46% vol hydroalcoholic solution in
      their natural concentrations. Omission experiments further confirmed beta
      damascenone and ethyl acetate as the key odorants and revealed the significance
      of the entire group of esters, particularly ethyl lactate, geosmin, acetic acid,
      and 2-methylpropanoic acid, for the overall aroma of the light aroma type Chinese
      liquor. 

PMID- 24909922
TI  - Molecular mechanisms involved in Bacillus subtilis biofilm formation.
AB  - Biofilms are the predominant lifestyle of bacteria in natural environments, and
      they severely impact our societies in many different fashions. Therefore, biofilm
      formation is a topic of growing interest in microbiology, and different bacterial
      models are currently studied to better understand the molecular strategies that
      bacteria undergo to build biofilms. Among those, biofilms of the soil-dwelling
      bacterium Bacillus subtilis are commonly used for this purpose. Bacillus subtilis
      biofilms show remarkable architectural features that are a consequence of
      sophisticated programmes of cellular specialization and cell-cell communication
      within the community. Many laboratories are trying to unravel the biological role
      of the morphological features of biofilms, as well as exploring the molecular
      basis underlying cellular differentiation. In this review, we present a general
      perspective of the current state of knowledge of biofilm formation in B. subtilis
      and thereby placing a special emphasis on summarizing the most recent discoveries
      in the field. 

PMID- 24909926
TI  - A shift from magnitude to sign epistasis during adaptive evolution of a bacterial
      social trait.
AB  - Although the importance of epistasis in evolution has long been recognized,
      remarkably little is known about the processes by which epistatic interactions
      evolve in real time in specific biological systems. Here, we have characterized
      how the epistatic fitness relationship between a social gene and an adapting
      genome changes radically over a short evolutionary time frame in the social
      bacterium Myxococcus xanthus. We show that a highly beneficial effect of this
      social gene in the ancestral genome is gradually reduced--and ultimately reversed
      into a deleterious effect--over the course of an experimental adaptive trajectory
      in which a primitive form of novel cooperation evolved. This reduction and
      reversal of a positive social allelic effect is driven solely by changes in the
      genetic context in which the gene is expressed as new mutations are sequentially
      fixed during adaptive evolution, and explicitly demonstrates a significant
      evolutionary change in the genetic architecture of an ecologically important
      social trait.

PMID- 24909924
TI  - Transcriptome profiling of pyrethroid resistant and susceptible mosquitoes in the
      malaria vector, Anopheles sinensis.
AB  - BACKGROUND: Anopheles sinensis is a major malaria vector in China and other
      Southeast Asian countries, and it is becoming increasingly resistant to the
      insecticides used for agriculture, net impregnation, and indoor residual spray.
      Very limited genomic information on this species is available, which has hindered
      the development of new tools for resistance surveillance and vector control. We
      used the 454 GS FLX system and generated expressed sequence tag (EST) databases
      of various life stages of An. sinensis, and we determined the transcriptional
      differences between deltamethrin resistant and susceptible mosquitoes. RESULTS:
      The 454 GS FLX transcriptome sequencing yielded a total of 624,559 reads (average
      length of 290 bp) with the pooled An. sinensis mosquitoes across various
      development stages. The de novo assembly generated 33,411 contigs with average
      length of 493 bp. A total of 8,057 ESTs were generated with Gene Ontology (GO)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation. A total of 2,131
      ESTs were differentially expressed between deltamethrin resistant and susceptible
      mosquitoes collected from the same field site in Jiangsu, China. Among these
      differentially expressed ESTs, a total of 294 pathways were mapped to the KEGG
      database, with the predominant ESTs belonging to metabolic pathways. Furthermore,
      a total of 2,408 microsatellites and 15,496 single nucleotide polymorphisms
      (SNPs) were identified. CONCLUSIONS: The annotated EST and transcriptome
      databases provide a valuable genomic resource for further genetic studies of this
      important malaria vector species. The differentially expressed ESTs associated
      with insecticide resistance identified in this study lay an important foundation
      for further functional analysis. The identified microsatellite and SNP markers
      will provide useful tools for future population genetic and comparative genomic
      analyses of malaria vectors.

PMID- 24909927
TI  - Caregiver experiences of supporting adults with intellectual disabilities in
      pain.
AB  - BACKGROUND: Caregivers have an intimate knowledge of the individuals they care
      for and are therefore an important source of information on pain experiences.
      They are often relied upon to recognize pain-related behaviours and report them,
      but little is known as to how they experience their role. METHODS: Information
      was collected from 11 caregivers using semi-structured interviews about their
      experiences of caring for adults with intellectual disabilities who were
      suspected or definitely in pain. Transcripts were analysed using Interpretative
      Phenomenological Analysis. RESULTS: Six superordinate themes were identified from
      participants' experiences: suffering in silence; searching for meaning to explain
      the complaint; knowledge and skills needed to recognize and manage pain;
      perceptions of the pain experience; acting to try and reduce pain; and the
      emotional impact of pain. CONCLUSIONS: There seems an art to detect pain using
      existing skills and knowledge of the individual's ways of expressing pain.
      Despite best efforts, recognizing and treating pain was experienced as complex
      and ambiguous. Some caregivers described a negative emotional impact and
      dissatisfaction with the management of pain by health care services.

PMID- 24909928
TI  - Dissecting aortic aneurysm induced by N-(2-aminoethyl) ethanolamine in rat: Role
      of defective collagen during development.
AB  - BACKGROUND: Dissecting aortic aneurysm (DAA) is a tear in the wall of the aorta
      that causes blood to flow, or "dissect," between the medial layers of the media.
      METHODS: Pregnant rats (dams) were treated with the industrial chemical n-(2
      aminoethyl) ethanolamine (AEEA) by intraperitoneal injection or gavage. The
      histology and pathology of aorta in the thorax from newborn pups were examined.
      Aortas of fetuses of gestational day 20 from dams exposed to AEEA were harvested
      for immunohistochemical staining and native Western blot to study the changes of
      collagen type 1 and type 3 in aorta. RESULTS: Dissecting aortic aneurysm of
      newborn rats was induced by treating with AEEA through intraperitoneal injection
      or gavage. The incidence of DAA reached 100% in live pups at the high dose by
      means of gavage of AEEA, but without lethality compared with intraperitoneal
      injection. A grading system for the dose-response of DAA lesions associated with
      AEEA by gavage was established. Gestational day 20 fetuses from treated dams
      showed a decreased content and altered distribution of medial and adventitial
      collagen type 1 and 3 in aorta by immunohistochemistry; this decrease was
      confirmed by native Western blot. CONCLUSION: This in vivo model of spontaneous
      aortic dissection bears striking similarities histologically to human aortic
      dissection. As such, the model conceivably could contribute to elucidating the
      mechanisms of DAA formation and to exploring diagnostic and therapeutic
      strategies. The pathogenesis of AEEA-induced DAA may be related to defects in the
      normal developmental progression of collagen types 1 and 3 in the vascular wall.

PMID- 24909929
TI  - Mesoporous spherical Li4Ti5O12 as high-performance anodes for lithium-ion
      batteries.
AB  - Porous microspherical Li4Ti5O12 aggregates (LTO-PSA) can be successfully prepared
      by using porous spherical TiO2 as a titanium source and lithium acetate as a
      lithium source followed by calcinations. The synthesized LTO-PSA possess
      outstanding morphology, with nanosized, porous, and spherical distributions, that
      allow good electrochemical performances, including high reversible capacity, good
      cycling stability, and impressive rate capacity, to be achieved. The specific
      capacity of the LTO-PSA at 30 C is as high as 141 mA h g(-1), whereas that of
      normal Li4Ti5O12 powders prepared by a sol-gel method can only achieve 100 mA h
      g(-1). This improved rate performance can be ascribed to small Li4Ti5O12
      nanocrystallites, a three-dimensional mesoporous structure, and enhanced ionic
      conductivity.

PMID- 24909931
TI  - Suicide and accidental death in Australia's rural farming communities: a review
      of the literature.
AB  - INTRODUCTION: Australia's farmers constitute a heterogeneous group within the
      rural population. This literature review incorporates four broad areas: an
      understanding of farming communities, families and individuals and the contexts
      in which they live and work; an exploration of the challenges to morbidity and
      mortality that these communities face; a description of the patterns of suicide
      and accidental death in farming communities; and an outline of what is missing
      from the current body of research. Recommendations will be made on how these gaps
      may be addressed. METHODS: In developing this comprehensive literature review, a
      snowballing and saturation approach was adopted. Initial search terms included
      suicid*, farm*, accident*, fatal*, death, sudden death, rural OR remote,
      Australia and NOT Australia. Databases searched included SCOPUS, PubMed, Proquest
      and SafetyLit; research from 1995 onwards was examined for relevance. Earlier
      seminal texts were also included. Reference lists of retrieved articles were
      searched and citations explored for further relevant research material. The
      primary focus was on Australian peer-reviewed research with supplementary grey
      literature. International material was used as examples. RESULTS: The literature
      variously describes farmers as members of both rural farming communities and
      farming families, and as individuals within an occupational classification.
      Within each of these classifications, there is evidence of the cumulative impact
      of a multiplicity of social, geographical and psychological factors relating to
      work, living and social arrangements that impact the health and wellbeing of
      Australia's farmers and their families, particularly accidental death and
      suicide. Research consistently demonstrates traumatic death to be at a greater
      rate than in the general Australian population, with reductions found more
      recently in some modes of farming-related accidental death. Patterns of
      accidental death and suicide are commonly linked to the changing shape of
      contemporary farming. Suicide rates are also frequently described in relation to
      lethality and accessibility of means. The limitations of suicide and accidental
      death data are considerable. CONCLUSION: While there is consistent reporting of
      heightened levels of risk for suicide and accidental death in farming communities
      the limitations of the research remain significant. There are substantial gaps in
      current knowledge, and the body of research to date lacks clarity, inclusiveness
      and contextual specificity. Absent from the literature is any investigation of
      the impact of these frequently preventable deaths on the families and communities
      in which they occur. Recommendations for future research are suggested.

PMID- 24909930
TI  - Impact of biological therapy on spondyloarthritis.
AB  - PURPOSE: In this review, we focus on the clinical and radiological aspects
      related to the biological therapy of ankylosing spondylitis (AS), axial
      spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: A review was
      carried out in the main medical databases to evaluate the available literature.
      RESULTS: Even if there is emerging interest for the role of biological agents
      other than tumour necrosis factor (TNF)-alpha inhibitors in spondyloarthritis,
      anti-TNF-alpha treatment is currently the only effective therapy for patients in
      whom conventional therapy with non-steroideal anti-inflammatory drugs (NSAIDs)
      has failed. Nevertheless, the potential impact of earlier treatment and the best
      drugs or combinations of drugs for preventing radiographic progression in SpA are
      yet to be determined. CONCLUSIONS: Anti-TNF-alpha treatment is currently used
      with efficacy in the greater part of patients with SpA. In these patients,
      availability of biological treatment is limited on the bases of potential
      toxicity and cost. On the basis of clinical trials, biologics other than TNF
      alpha inhibitors can currently not be recommended for the treatment of SpA.

PMID- 24909932
TI  - Skin infections in high school wrestlers: a nurse practitioner's guide to
      diagnosis, treatment, and return to participation.
AB  - PURPOSE: To provide nurse practitioners (NPs) with a current guide for the
      diagnosis and treatment of high school wrestlers who present with common skin
      infections and to familiarize NPs with the National Federation of High School
      Associations Sports Medicine Advisory Committee return to participation guide and
      medical release form. DATA SOURCES: Literature review of evidence-based research,
      journal articles, and reference texts related to skin lesions and high school
      wrestlers. CONCLUSIONS: High school wrestlers with skin infections present in a
      variety of clinical settings. Improperly diagnosed and/or managed skin infections
      have the potential to get worse and continue to spread among teammates. Accurate
      diagnosis and treatment in combination with the use of a return to participation
      guide can improve outcomes and return the wrestler to participation sooner.
      IMPLICATIONS FOR PRACTICE: NPs have a responsibility to accurately diagnose and
      treat skin lesions in a timely, safe, and efficient manner. In wrestling,
      athletes are exposed to unique opportunities to develop skin infections. With a
      working knowledge of the clinical presentation, diagnostic testing, and return to
      participation recommendations for common skin diseases, spread of skin infections
      to other wrestlers can be prevented and the athlete can return to play safely.

PMID- 24909933
TI  - Effects of phenol and meta-cresol depletion on insulin analog stability at
      physiological temperature.
AB  - The stability of three commercial "fast-acting" insulin analogs, insulin lispro,
      insulin aspart, and insulin glulisine, was studied at various concentrations of
      phenolic preservatives (phenol and/or meta-cresol) during 9 days of incubation at
      37  degrees C. The analysis by both size-exclusion and reversed-phase
      chromatography showed degradation of lispro and aspart that was inversely
      dependent on the concentration of phenolic preservatives. Insulin glulisine was
      much more stable than the other analogs and showed minimal degradation even in
      the absence of phenolic preservatives. With sedimentation velocity
      ultracentrifugation, we determined the preservatives' effect on the insulins'
      self-assembly. When depleted of preservatives, insulin glulisine dissociates from
      higher molecular weight species into a number of intermediate molecular weight
      species, in between monomer and hexamer, whereas insulin aspart and insulin
      lispro dissociate into monomers and dimers. Decreased stability of insulin lispro
      and insulin aspart seems to be because of the extent of dissociation when
      depleted of preservative. Insulin glulisine's dissociation to intermediate
      molecular weight species appears to help minimize its degradation during
      incubation at 37  degrees C.

PMID- 24909934
TI  - Oncobiguanides: Paracelsus' law and nonconventional routes for administering
      diabetobiguanides for cancer treatment.
AB  - "The dose makes the poison", the common motto of toxicology first expressed by
      Paracelsus more than 400 years ago, may effectively serve to guide potential
      applications for metformin and related biguanides in oncology. While Paracelsus'
      law for the dose-response effect has been commonly exploited for the use of some
      anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate),
      the opposite scenario also holds true; in other words, higher doses of non
      oncology drugs, such as anti-diabetic biguanides, might exert direct anti
      neoplastic effects. Here, we propose that, as for any drug, there is a dose range
      for biguanides that is without any effect, one corresponding to
      "diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in
      type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect
      inhibition of insulin and growth factor-dependent cancer growth) but with minimal
      toxicity and another corresponding to "oncobiguanides" with pharmacological
      (i.e., direct and strong anticancer activity against cancer cells) as well as
      toxic effects. Considering that biguanides demonstrate a better safety profile
      than most oncology drugs in current use, we should contemplate the possibility of
      administering biguanides through non-conventional routes (e.g., inhaled for
      carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive
      therapy, rectal suppositories for rectal cancer) to unambiguously investigate the
      therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps
      then, the oncobiguanides, as we call them here, could be viewed as a
      mechanistically different type of anti-cancer drugs employed at doses notably
      higher than those used chronically when functioning as diabetobiguanides. 

PMID- 24909935
TI  - Population-based epidemiology of amyotrophic lateral sclerosis (ALS) in an ageing
      Europe--the French register of ALS in Limousin (FRALim register).
AB  - BACKGROUND AND PURPOSE: The main objective of establishing the French register of
      amyotrophic lateral sclerosis (ALS) in the Limousin region (FRALim), was to
      assess the incidence of ALS, in this ageing region of Europe, over a 12-year
      period (2000-2011). METHODS: Patients were included if they lived in Limousin at
      the time of diagnosis of ALS according to El Escorial revised criteria and were
      identified by at least one of the following sources: (i) the French national body
      coordinating ALS referral centres; (ii) public and private hospitals in the
      region; (iii) health insurance data related to long-term diseases. RESULTS: The
      FRALim register identified 279 incident cases (2000-2011). The crude and European
      population standardized incidences of ALS were as high as 3.19/100,000 person
      years of follow-up (95% CI 2.81-3.56) and 2.58/100,000 person-years of follow-up
      (95% CI 2.27-2.89) respectively. Median age at onset was 70.8 years
      (interquartile range 63.1-77.1). The standardized sex incidence ratio
      (male/female) was 1.3 overall, but 1.1 under the age of 65 years, 1.7 between 65
      and 75 years and 1.9 above 75 years. The exhaustiveness of the register has been
      estimated at 98.4% (95% CI 95.6-99.4) by capture-recapture analysis. CONCLUSION:
      It was possible for the first time in France to monitor accurately the incidence
      of ALS over a long time period. It appears to be in the upper range of data
      reported in western countries. Patterns displayed here might anticipate the
      epidemiology of ALS in ageing western countries.

PMID- 24909936
TI  - A three-protein biomarker panel assessed in diagnostic tissue predicts death from
      prostate cancer for men with localized disease.
AB  - Only a minority of prostate cancers lead to death. Because no tissue biomarkers
      of aggressiveness other than Gleason score are available at diagnosis, many
      nonlethal cancers are treated aggressively. We evaluated whether a panel of
      biomarkers, associated with a range of disease outcomes in previous studies,
      could predict death from prostate cancer for men with localized disease. Using a
      case-only design, subjects were identified from three Australian epidemiological
      studies. Men who had died of their disease, "cases" (N = 83), were matched to
      "referents" (N = 232), those who had not died of prostate cancer, using incidence
      density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1,
      MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC).
      Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for
      age, Gleason score, and stage and to estimate survival probabilities. Expression
      of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14
      5.54, P = 0.02 and 3.08, 95% CI 1.41-6.95, P = 0.005, respectively), whereas
      AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20
      0.96, P = 0.04). Analyzing all markers under a combined model indicated that the
      three markers were independent predictors of prostate cancer death and survival.
      For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53
      expression in diagnostic tissue by IHC could potentially improve estimates of
      risk of dying from prostate cancer based only on Gleason score and clinical
      stage. 

PMID- 24909937
TI  - Synthesis of spirocyclic enones by rhodium-catalyzed dearomatizing oxidative
      annulation of 2-alkenylphenols with alkynes and enynes.
AB  - The dearomatizing oxidative annulation of 2-alkenylphenols with alkynes and
      enynes proceeds with high yields and regioselectivities under Rh(III) catalysis.
      These reactions are successful using Cu(OAc)2 or air as the stoichiometric
      oxidant, and provide spirocyclic enones, the basic ring system of which appears
      in several natural products. Application of this process to the preparation of a
      highly functionalized tetracycle is also demonstrated. 

PMID- 24909938
TI  - Thermolubricity of gas monolayers on graphene.
AB  - Nanofriction of Xe, Kr and N2 monolayers deposited on graphene was explored with
      a quartz crystal microbalance (QCM) at temperatures between 25 and 50 K. Graphene
      was grown by chemical vapour deposition and transferred to the QCM electrodes
      with a polymer stamp. It was found to strongly adhere to the gold electrodes at
      temperatures as low as 5 K and at frequencies up to 5 MHz. At low temperatures,
      the Xe monolayers are fully pinned to the graphene surface. Above 30 K, the Xe
      film slides and the depinning onset coverage beyond which the film starts sliding
      decreases with temperature. Similar measurements repeated on bare gold show an
      enhanced slippage of the Xe films and a decrease of the depinning temperature
      below 25 K. Nanofriction measurements of Kr and N2 confirm this scenario. This
      thermolubric behaviour is explained in terms of a recent theory of the size
      dependence of static friction between adsorbed islands and crystalline
      substrates.

PMID- 24909939
TI  - The role of neck dissection and postoperative adjuvant radiotherapy in cN0
      patients with PNI-positive squamous cell carcinoma of the oral cavity.
AB  - INTRODUCTION: Loco-regional recurrence is one of the main causes of treatment
      failure in patients with oral squamous cell carcinoma (OSCC). Perineural invasion
      (PNI) is widely accepted as an oncologic feature strongly associated with
      aggressive behavior, disease recurrence and poorer prognosis. This study
      investigated the role of PNI in OSCC patients, regarding the controversial issues
      of its impact on loco-regional recurrence, neck management and postoperative
      adjuvant treatment decisions. MATERIALS AND METHODS: A total of 367 patients with
      OSCC were analyzed at a tertiary care cancer center with the purpose of
      investigating the prognostic significance of PNI regarding neck involvement,
      local recurrence, regional recurrence and disease-specific survival. Two
      subgroups of 39 patients each, one with PNI-positive and one with PNI-negative
      tumors, but otherwise similar histopathological features, were retrospectively
      analyzed. All patients had negative resection margins, no lympho-vascular
      invasion and pN0-1 disease without ECS. The mean follow up period was 42.7
      months. RESULTS: Univariate and multivariate analyses showed that the perineural
      invasion was an independent prognostic factor for lymph node metastasis and
      regional recurrence, but not for local recurrence. Elective neck dissection was
      strongly associated with a lower risk of regional recurrence, as well as with a
      better disease-specific survival, in PNI-positive cN0 patients. Postoperative
      radiation therapy appears not to reduce the incidence of recurrence. CONCLUSION:
      Perineural invasion should be considered as an independent predictor for cervical
      lymph node involvement. Elective neck dissection could therefore be an indicator
      in improving neck control and subsequently disease-specific survival in cN0
      patients with PNI-positive SCC.

PMID- 24909940
TI  - Comment on the article "salivary gland transfer to prevent radiation-induced
      xerostomia: a systematic review and meta-analysis" by Sood AJ et al. published in
      Oral Oncology 50 (2014) 77-83.

PMID- 24909941
TI  - Clinical results of percutaneous transluminal angioplasty for thromboangiitis
      obliterans in arteries above the knee.
AB  - OBJECTIVE: This study was designed to retrospectively investigate whether
      percutaneous transluminal angioplasty (PTA) is efficacious and safe for the
      treatment of atypical thromboangiitis obliterans (ATAO) in arteries with
      occlusion of long segments. METHODS: From January 2011 to July 2013, 9
      consecutive male patients with ATAO involving the external iliac and superficial
      femoral arteries were treated by PTA alone, without stent placement. Their mean
      age was 35 years (range, 24-47 years). Preoperative symptoms included severe
      claudication (n = 2), ischemic pain at rest (n = 4), and ischemic ulcers (n = 3).
      No any infrapopliteal interventions were performed besides the proximal
      intervention. RESULTS: Technical success using PTA was achieved in 100% of cases
      with occluded arteries, and there were no periprocedural complications. Clinical
      improvement was observed postoperatively with a significant improvement in
      Rutherford categories (range, 2-3) and significantly increased ankle-brachial
      indexes, from 0.59 +/- 0.14 to 0.91 +/- 0.17 (p < 0.01). Ischemic ulcers in three
      patients healed 3-5 months postoperatively. No recurrent ischemic ulcer was
      observed, and no amputation was performed in these patients. At follow-up
      examination (average, 20.9 months), restenosis of the superficial femoral artery
      was diagnosed in only one patient who continued with a conservative medication
      regimen and refused additional interventional treatment because his physical
      symptoms were minor. CONCLUSION: PTA might be feasible and safe for the treatment
      of ATAO patients, and appears to provide positive clinical results at an average
      follow-up of 20.9 months.

PMID- 24909942
TI  - An automated technique for carotid far wall classification using grayscale
      features and wall thickness variability.
AB  - PURPOSE: To test a computer-aided diagnostic method for differentiating
      symptomatic from asymptomatic carotid B-mode ultrasonographic images. METHODS:
      Our system (called Atheromatic) automatically computed the intima-media thickness
      (IMT) of the carotid far wall using AtheroEdge, calculated nonlinear features
      based on higher order spectra, and used these features and IMT and IMT
      variability (IMTVpoly ) to associate each image to a feature vector that was then
      labeled as symptomatic or asymptomatic (Sym/Asym) by a multiclassifiers system.
      We tested this method on a database of 118 carotid artery images from 37
      symptomatic and 22 asymptomatic patients RESULTS: The highest accuracy (99.1%)
      was obtained by the support vector machine classifier using seven features. These
      features, relevant to discriminate Sym/Asym, included IMT and IMTVpoly , along
      with the bispectral entropies of the distal wall image at 77 degrees , 78 degrees
      , and 79 degrees  angles. CONCLUSIONS: Classification in Sym/Asym of the far
      carotid wall is feasible and accurate and could be useful for the early detection
      of atherosclerosis and to identify patients with higher cardiovascular risk.

PMID- 24909943
TI  - An efficient synthetic route to stable bis(carbene)borylenes [(L1)(L2)BH].
AB  - Two-electron reduction of bis(carbene) boronium salts allows for the preparation
      of unsymmetrically substituted nucleophilic boron derivatives of type (L1)(L2)BH,
      which are characterized by X-ray crystallography. A single electron reduction of
      the same starting materials leads to the corresponding boron-centered radical
      cations (L1)(L2)BH(+), X(-). 

PMID- 24909944
TI  - A multiplexed chip-based assay system for investigating the functional
      development of human skeletal myotubes in vitro.
AB  - This report details the development of a non-invasive in vitro assay system for
      investigating the functional maturation and performance of human skeletal
      myotubes. Data is presented demonstrating the survival and differentiation of
      human myotubes on microscale silicon cantilevers in a defined, serum-free system.
      These cultures can be stimulated electrically and the resulting contraction
      quantified using modified atomic force microscopy technology. This system
      provides a higher degree of sensitivity for investigating contractile waveforms
      than video-based analysis, and represents the first system capable of measuring
      the contractile activity of individual human muscle myotubes in a reliable, high
      throughput and non-invasive manner. The development of such a technique is
      critical for the advancement of body-on-a-chip platforms toward application in
      pre-clinical drug development screens. 

PMID- 24909945
TI  - Rapid magnetic bead based sample preparation for automated and high throughput N
      glycan analysis of therapeutic antibodies.
AB  - Full automation to enable high throughput N-glycosylation profiling and
      sequencing with good reproducibility is vital to fulfill the contemporary needs
      of the biopharmaceutical industry and requirements of national regulatory
      agencies. The most prevalently used glycoanalytical methods of capillary
      electrophoresis and hydrophilic interaction liquid chromatography, while very
      efficient, both necessitate extensive sample preparation and cleanup, including
      glycoprotein capture, N-glycan release, fluorescent derivatization, purification,
      and preconcentration steps during the process. Currently used protocols to
      fulfill these tasks require multiple centrifugation and vacuum-centrifugation
      steps, making liquid handling robot mediated automated sample preparation
      difficult and expensive. In this paper we report on a rapid magnetic bead based
      sample preparation approach that enables full automation including all the
      process phases just in a couple of hours without requiring any centrifugation
      and/or vacuum centrifugation steps. This novel protocol has been compared to
      conventional glycan sample preparation strategies using standard glycoproteins
      (IgG, fetuin, and RNase B) and featured rapid processing time, high release and
      labeling efficiency, good reproducibility, and the potential of easy automation. 

PMID- 24909946
TI  - Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in
      most untreated HIV-1 infected individuals.
AB  - BACKGROUND: The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted
      by broadly neutralizing antibodies. However, the localization of this epitope in
      a hydrophobic environment seems to hamper the elicitation of these antibodies in
      HIV infected individuals.We have quantified and characterized anti-MPER
      antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived
      proteins expressed on the surface of 293T cells. Longitudinal plasma samples from
      35 HIV-1 infected individuals were assayed for MPER recognition and MPER
      dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER
      sequences. RESULTS: Miniproteins devoid of the cysteine loop of gp41 exposed the
      MPER on 293T cell membrane. Anti-MPER antibodies were identified in most
      individuals and were stable when analyzed in longitudinal samples. The magnitude
      of the responses was strongly correlated with the global response to the HIV-1
      envelope glycoprotein, suggesting no specific limitation for anti-MPER
      antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety
      and a wide presence of antibodies against the 2F5 epitope. However, antibody
      titers failed to correlate with 2F5-blocking activity and, more importantly, with
      the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER
      sequence; suggesting a strong functional heterogeneity in anti-MPER humoral
      responses. CONCLUSIONS: Anti-MPER antibodies can be detected in the vast majority
      of HIV-1 infected individuals and are generated in the context of the global anti
      Env response. However, the neutralizing capacity is heterogeneous suggesting that
      eliciting neutralizing anti-MPER antibodies by immunization might require
      refinement of immunogens to skip nonneutralizing responses.

PMID- 24909948
TI  - Female extra-pair mating: adaptation or genetic constraint?
AB  - Why do females of so many socially monogamous species regularly engage in matings
      outside the pair bond? This question has puzzled behavioural ecologists for more
      than two decades. Until recently, an adaptionist's point of view prevailed: if
      females actively seek extra-pair copulations, as has been observed in several
      species, they must somehow benefit from this behaviour. However, do they? In this
      review, we argue that adaptive scenarios have received disproportionate research
      attention, whereas nonadaptive phenomena, such as pathological polyspermy, de
      novo mutations, and genetic constraints, have been neglected by empiricists and
      theoreticians alike. We suggest that these topics deserve to be taken seriously
      and that future work would benefit from combining classical behavioural ecology
      with reproductive physiology and evolutionary genetics. 

PMID- 24909947
TI  - A latent class analysis to empirically describe eating disorders through
      developmental stages.
AB  - OBJECTIVES: The current standards for classifying eating disorders were primarily
      informed by adult, clinical study populations, while it is unknown whether an
      empirically based classification system can be supported across preadolescence
      through young adulthood. Using latent class analyses, we sought to empirically
      classify disordered eating in females from preadolescence to young adulthood, and
      assess the association between classes and adverse outcomes. METHOD: Latent class
      models were fit using observations from the 9,039 girls participating in the
      growing up today study, an on-going cohort following participants annually or
      biennially since 1996 when they were ages 9-14 years. Associations between
      classes and drug use, binge drinking, and depressive symptoms were assessed using
      generalized estimating equations. RESULTS: Across age groups, there was evidence
      of six classes: a large asymptomatic class, a class characterized by shape/weight
      concerns, a class characterized by overeating without loss of control, and three
      resembling full and subthreshold binge eating disorder, purging disorder, and
      bulimia nervosa. Relative prevalences of classes varied across developmental
      stages, with symptomatic classes increasing in prevalence with increasing age.
      Symptomatic classes were associated with concurrent and incident drug use, binge
      drinking, and high depressive symptoms. DISCUSSION: A classification system
      resembling broader definitions of DSM-5 diagnoses along with two further
      subclinical symptomatic classes may be a useful framework for studying disordered
      eating among adolescent and young adult females.

PMID- 24909949
TI  - Umeclidinium bromide and vilanterol in combination for the treatment of chronic
      obstructive pulmonary disease.
AB  - Drugs from the two major classes of bronchodilator; umeclidinium, a long-acting
      muscarinic antagonist (LAMA), and vilanterol, a long-acting beta2 agonist (LABA),
      have been combined in a single inhaler device for once-daily use in chronic
      obstructive pulmonary disease (COPD). These drugs have been proven safe and well
      tolerated in patients with COPD and show an enhanced improvement in FEV1 when
      compared to either drug in isolation and when compared with an established LAMA
      drug. In this article, we discuss the data supporting this combination inhaler
      and also review alternative combined LAMA/LABA options. We discuss where these
      agents are likely to find a place in the current therapy of COPD and where the
      future is likely to lead with these and other therapies.

PMID- 24909951
TI  - Multimodal medical information retrieval with unsupervised rank fusion.
AB  - Modern medical information retrieval systems are paramount to manage the
      insurmountable quantities of clinical data. These systems empower health care
      experts in the diagnosis of patients and play an important role in the clinical
      decision process. However, the ever-growing heterogeneous information generated
      in medical environments poses several challenges for retrieval systems. We
      propose a medical information retrieval system with support for multimodal
      medical case-based retrieval. The system supports medical information discovery
      by providing multimodal search, through a novel data fusion algorithm, and term
      suggestions from a medical thesaurus. Our search system compared favorably to
      other systems in 2013 ImageCLEFMedical. 

PMID- 24909950
TI  - Quantitative assessment of CYP2D6 polymorphisms and risk of Alzheimer's disease:
      a meta-analysis.
AB  - BACKGROUND: CYP2D6 gene encoding CYP2D6 enzyme belonging to the cytochrome P450
      system has aroused long attention being a candidate gene for Alzheimer's disease
      (AD), but the results remain inconsistent and underpowered. OBJECTIVES: To
      investigate the contradictory results, the effect of single CYP2D6 polymorphism-
      CYP2D6*4, together with CYP2D6 phenotypes on the risk of AD, was evaluated using
      a meta-analysis. METHODS: Electronic database search of PubMed, Embase and
      Cochrane Library was conducted up to Apr 17, 2014. Odds ratio (OR) along with the
      95% confidence interval (CI) was calculated. Subgroup analysis was performed to
      examine the impact of CYP2D6 variants on different ethnic. Meta-regression was
      performed to explore possible source of heterogeneity. RESULTS: A total of 11
      studies involving 643AD cases and 1375 controls were included for CYP2D6*4
      polymorphism, and 4 studies consisted of 411AD cases and 603 controls were
      included for CYP2D6 phenotypes. With respect to CYP2D6*4 polymorphism,
      significantly increased risk of AD was found in allelic contrast model of A vs. G
      (OR=1.29, 95%CI=1.03-1.62, P=0.026), co-dominant genetic model AA vs. GG
      (OR=1.91, 95%CI=1.04-3.51, P=0.038); and recessive genetic model AA vs. AG+GG
      (OR=1.88, 95%CI=1.03-3.46, P=0.041) in the overall populations. Similar results
      were also indicated in subgroup analysis in Caucasians. As for CYP2D6 phenotypes,
      no significant association with AD was revealed. CONCLUSIONS: Our data support
      that the CYP2D6*4 polymorphism but not CYP2D6 phenotypes might be associated with
      increased AD risk, particularly in Caucasian populations.

PMID- 24909952
TI  - Uneven drying of zygotic embryos and embryonic axes of recalcitrant seeds:
      challenges and considerations for cryopreservation.
AB  - Cryopreservation is the most promising option for the long-term germplasm
      conservation of recalcitrant-seeded species. However, the variable post-cryo
      success achieved with the excised zygotic explants traditionally used for
      cryopreservation has been a concern for some time. Differential drying rates
      amongst explants of different species, uneven drying amongst explants within a
      batch of seeds and uneven drying across tissues within individual embryos could
      be contributory factors to this variable success and these phenomena form the
      foci of the present study. Using zygotic explants from a range of recalcitrant
      seeded species, which included sub-tropical dicotyledonous trees and sub-tropical
      monocotyledonous geophytes, the study showed that embryo morphology and anatomy
      are critical determinants of the drying characteristics of the different tissues
      composing the explant and hence, post-cryo survival. The results suggest that the
      rates of drying of explants to water contents (WCs) in the theoretically optimal
      range for successful cryopreservation are species-specific, and that more rapid
      drying rates may promote post-cryo survival. However, the large variation in WC
      amongst individual explants in bulk samples challenges the selection of the
      theoretically optimum WC for cryopreservation. As a consequence of differential
      drying rates across the different tissues composing explants, either lethal ice
      crystal damage or desiccation damage may sometimes be likely in tissues
      responsible for the onwards development of the embryo. Drying times for
      cryopreservation of such explants should, therefore, be selected on the basis of
      WC of segments containing root or shoot meristem, rather than embryo bulk WC.
      Drying intensity and duration also interact with explant morphology and
      embryo/axis size and anatomy to bring about - or preclude - post-cryo survival. 

PMID- 24909954
TI  - Pathology and mortality associated with the mauve stinger jellyfish Pelagia
      noctiluca in farmed Atlantic salmon Salmo salar L.

PMID- 24909953
TI  - Bone tissue engineering with a collagen-hydroxyapatite scaffold and culture
      expanded bone marrow stromal cells.
AB  - Osteoprogenitor cells combined with supportive biomaterials represent a promising
      approach to advance the standard of care for bone grafting procedures. However,
      this approach faces challenges, including inconsistent bone formation, cell
      survival in the implant, and appropriate biomaterial degradation. We have
      developed a collagen-hydroxyapatite (HA) scaffold that supports consistent
      osteogenesis by donor-derived osteoprogenitors, and is more easily degraded than
      a pure ceramic scaffold. Herein, the material properties are characterized as
      well as cell attachment, viability, and progenitor distribution in vitro.
      Furthermore, we examined the biological performance in vivo in a critical-size
      mouse calvarial defect. To aid in the evaluation of the in-house collagen-HA
      scaffold, the in vivo performance was compared with a commercial collagen-HA
      scaffold (Healos((r)) , Depuy). The in-house collagen-HA scaffold supported
      consistent bone formation by predominantly donor-derived osteoblasts, nearly
      completely filling a 3.5 mm calvarial defect with bone in all samples (n = 5)
      after 3 weeks of implantation. In terms of bone formation and donor cell
      retention at 3 weeks postimplantation, no statistical difference was found
      between the in-house and commercial scaffold following quantitative
      histomorphometry. The collagen-HA scaffold presented here is an open and well
      defined platform that supports robust bone formation and should facilitate the
      further development of collagen-hydroxyapatite biomaterials for bone tissue
      engineering.

PMID- 24909955
TI  - Rhamnose glycoconjugates for the recruitment of endogenous anti-carbohydrate
      antibodies to tumor cells.
AB  - Immunotherapy is a promising strategy for targeting tumors. One emerging approach
      is to harness the immune effector functions of natural antibodies to destroy
      tumor cells. Dinitrophenyl (DNP) and the galactose-alpha-1,3-galactose (alphaGal)
      epitope are two haptens that bind endogenous antibodies. One potential
      alternative is the deoxysugar L-rhamnose. We compared these candidates by using a
      biosensor assay to evaluate human sera for endogenous antibody concentration,
      antibody isotype distribution, and longevity of antibody-hapten interactions.
      Antibodies recognizing alpha-rhamnose are of equal or greater abundance and
      affinity as those recognizing alphaGal. Moreover, both rhamnose and alphaGal
      epitopes are more effective than DNP at recruiting the IgG antibody subtype.
      Exposure of tumor cells to rhamnose-bearing glycolipids and human serum promotes
      complement-mediated cytotoxicity. These data highlight the utility of alpha
      rhamnose-containing glycoconjugates to direct the immune system to target cells. 

PMID- 24909957
TI  - Safety, minimization, and awareness radiation training reduces fluoroscopy time
      during unilateral ureteroscopy.
AB  - OBJECTIVE: To determine the impact of Safety, Minimization and Awareness
      Radiation Training (SMART) on fluoroscopy time during unilateral uncomplicated
      ureteroscopy for urolithiasis performed by urology residents. MATERIALS AND
      METHODS: All consecutive ureteroscopy cases for urolithiasis meeting inclusion
      criteria and performed by first-year urology residents over a 2-year period were
      reviewed. Fluoroscopy times during SMART and without SMART were compared.
      RESULTS: A total of 202 ureteroscopy cases were reviewed. The mean patient age
      was 48.7 years. The mean stone diameter was 7.6 +/- 3.3 mm. The mean operating
      time was 79.8 +/- 34.3 minutes. The mean cumulative fluoroscopy time was 85.6 +/-
      36.9 seconds per case. A Spearman rank correlation identified 8 variables
      significantly correlated with fluoroscopy time, with the most significant
      correlation between shorter fluoroscopy time and SMART exposure (rho = 0.532; P
      <.001). Multivariate regression analysis (r = 0.701) revealed that fluoroscopy
      time was significantly shorter with SMART (P <.001). Post hoc comparisons
      revealed the fluoroscopy time of the cases performed during SMART (mean, 45
      seconds) to be significantly shorter than the fluoroscopy time of cases performed
      by the same residents before SMART (mean, 102 seconds; P = .005), and the
      fluoroscopy time of cases performed by residents the previous year with similar
      ureteroscopic experience but without SMART (mean, 78 seconds; P <.001).
      CONCLUSION: SMART reduces fluoroscopy time during unilateral uncomplicated
      ureteroscopy for urolithiasis performed by urology residents by 56%.

PMID- 24909956
TI  - Expression of dual nucleotides/cysteinyl-leukotrienes receptor GPR17 in early
      trafficking of cardiac stromal cells after myocardial infarction.
AB  - GPR17 is a G(i) -coupled dual receptor activated by uracil-nucleotides and
      cysteinyl-leukotrienes. These mediators are massively released into hypoxic
      tissues. In the normal heart, GPR17 expression has been reported. By contrast,
      its role in myocardial ischaemia has not yet been assessed. In the present
      report, the expression of GPR17 was investigated in mice before and at early
      stages after myocardial infarction by using immunofluorescence, flow cytometry
      and RT-PCR. Before induction of ischaemia, results indicated the presence of the
      receptor in a population of stromal cells expressing the stem-cell antigen-1 (Sca
      1). At early stages after ligation of the coronary artery, the receptor was
      expressed in Sca-1(+) cells, and cells stained with Isolectin-B4 and anti-CD45
      antibody. GPR17(+) cells also expressed mesenchymal marker CD44. GPR17 function
      was investigated in vitro in a Sca-1(+)/CD31(-) cell line derived from normal
      hearts. These experiments showed a migratory function of the receptor by
      treatment with UDP-glucose and leukotriene LTD4, two GPR17 pharmacological
      agonists. The GPR17 function was finally assessed in vivo by treating infarcted
      mice with Cangrelor, a pharmacological receptor antagonist, which, at least in
      part, inhibited early recruitment of GPR17(+) and CD45(+) cells. These findings
      suggest a regulation of heart-resident mesenchymal cells and blood-borne cellular
      species recruitment following myocardial infarction, orchestrated by GPR17.

PMID- 24909958
TI  - Editorial comment.

PMID- 24909959
TI  - Reply: To PMID 24909960.

PMID- 24909960
TI  - Can selective arterial clamping with fluorescence imaging preserve kidney
      function during robotic partial nephrectomy?
AB  - OBJECTIVE: To compare renal functional outcomes in robotic partial nephrectomy
      (RPN) with selective arterial clamping guided by near-infrared fluorescence
      (NIRF) imaging to a matched cohort of patients who underwent RPN without
      selective arterial clamping and NIRF imaging. METHODS: From April 2011 to
      December 2012, NIRF imaging-enhanced RPN with selective clamping was used in 42
      cases. Functional outcomes of successful cases were compared with a cohort of
      patients, matched by tumor size, preoperative estimated glomerular filtration
      rate (eGFR), functional kidney status, age, sex, body mass index, and American
      Society of Anesthesiologists score, who underwent RPN without selective clamping
      and NIRF imaging. RESULTS: In matched-pair analysis, selective clamping with NIRF
      was associated with superior kidney function at discharge, as demonstrated by
      postoperative eGFR (78.2 vs 68.5 mL/min/1.73 m(2); P = .04), absolute reduction
      of eGFR (-2.5 vs -14.0 mL/min/1.73 m(2); P <.01), and percent change in eGFR (
      1.9% vs -16.8%; P <.01). Similar trends were noted at 3 month follow-up, but
      these differences became nonsignificant (P[eGFR] = .07; P[absolute reduction of
      eGFR] = .10; and P[percent change in eGFR] = .07). In the selective clamping
      group, a total of 4 perioperative complications occurred in 3 patients, all of
      which were Clavien grade I-III. CONCLUSION: Use of NIRF imaging was associated
      with improved short-term renal functional outcomes when compared with RPN without
      selective arterial clamping and NIRF imaging. With this effect attenuated at
      later follow-up, randomized prospective studies and long-term assessment of
      kidney-specific functional outcomes are needed to further assess the benefits of
      this technology.

PMID- 24909961
TI  - Editorial comment.

PMID- 24909962
TI  - Editorial comment.

PMID- 24909963
TI  - Reply: To PMID 24909960.

PMID- 24909964
TI  - "Connecting the dots" from blood brain barrier dysfunction to neuroinflammation
      and Alzheimer's disease.

PMID- 24909966
TI  - Thermodynamics of adsorption of ionic surfactants at water/alkane interfaces.
AB  - On the basis of experimental data for the homologous series of
      alkyltrimethylammonium bromides (CnTAB) the equilibrium surface tension isotherms
      at three types of liquid-fluid interfaces are discussed: solution/air,
      solution/alkane vapor and solution/liquid alkane interfaces. It is shown that the
      adsorption characteristics can be described at all three interfaces by the same
      thermodynamic approach. In the presence of alkane molecules (in the liquid alkane
      phase or in the alkane vapor phase) the CnTAB adsorption layers can be best
      described by a co-adsorption of the alkane molecules. 

PMID- 24909965
TI  - Characterisation of terrestrial acidophilic archaeal ammonia oxidisers and their
      inhibition and stimulation by organic compounds.
AB  - Autotrophic ammonia oxidation is performed by two distinct groups of
      microorganisms: ammonia-oxidising archaea (AOA) and ammonia-oxidising bacteria
      (AOB). AOA outnumber their bacterial counterparts in many soils, at times by
      several orders of magnitude, but relatively little is known of their physiology
      due to the lack of cultivated isolates. Although a number of AOA have been
      cultivated from soil, Nitrososphaera viennensis was the sole terrestrial AOA in
      pure culture and requires pyruvate for growth in the laboratory. Here, we
      describe isolation in pure culture and characterisation of two acidophilic
      terrestrial AOA representing the Candidatus genus Nitrosotalea and their
      responses to organic acids. Interestingly, despite their close phylogenetic
      relatedness, the two Nitrosotalea strains exhibited differences in physiological
      features, including specific growth rate, temperature preference and to an
      extent, response to organic compounds. In contrast to N. viennensis, both
      Nitrosotalea isolates were inhibited by pyruvate but their growth yield increased
      in the presence of oxaloacetate. This study demonstrates physiological diversity
      within AOA species and between different AOA genera. Different preferences for
      organic compounds potentially influence the favoured localisation of ammonia
      oxidisers within the soil and the structure of ammonia-oxidising communities in
      terrestrial ecosystems. 

PMID- 24909967
TI  - Generation of monoclonal autoantibodies from Babesia rodhaini-infected mice.
AB  - The presence of anti-erythrocyte autoantibodies in animals infected with various
      Babesia species is well reported. However, the pathogenesis of autoantibodies in
      babesiosis is poorly understood. Here, we demonstrated that anti-erythrocyte
      immunoglobulin (Ig) M and IgG were present in B. rodhaini-infected mice at 6 and
      8 days after infection, respectively. Furthermore, we generated monoclonal
      antibodies against erythrocyte antigen from B. rodhaini-infected mice. Five
      clones were generated. By Western blotting analysis using whole erythrocyte
      antigens, one clone reacted with a broad band around 90-150 kDa, and the 2 clones
      reacted with a band larger than 150 kDa. B. rodhaini-infected mice and/or
      autoreactive monoclonal antibodies established in this study might be a powerful
      tool for in vivo pathogenesis studies of autoantibody development in infectious
      diseases. 

PMID- 24909968
TI  - Squamous cell carcinoma in a capybara (Hydrochoerus hydrochaeris).
AB  - A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed
      with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis.
      The capybara was euthanized, examined by computed tomography and necropsied; the
      tumor was examined histologically. Computed tomography showed a dense soft tissue
      mass with indistinct borders at the buttocks. Histological examination of the
      tumor revealed islands of invasive squamous epithelial tumor cells with a severe
      desmoplastic reaction. Based on the pathological findings, the mass was diagnosed
      as a squamous cell carcinoma. This is the first study to report squamous cell
      carcinoma in a capybara. 

PMID- 24909969
TI  - Efficacy of Malarone((r)) in dogs naturally infected with Babesia gibsoni.
AB  - The efficacy of Malarone((r)) alone and in combination with doxycycline (DOXY)
      against Babesia gibsoni infections was examined in 8 dogs. In all dogs except one
      treated with Malarone((r)), parasitemia decreased, and anemia improved soon after
      initiation of treatment. However, 3 of 4 dogs treated with Malarone((r))
      relapsed, and relapse was inhibited in 2 of 4 dogs treated with Malarone((r)) and
      DOXY. All relapsed dogs responded well to the second treatment, but 1 dog
      relapsed again and did not respond to the third treatment. Malarone((r)) may be
      useful for acute stage of B. gibsoni infections, and at least second repeating
      treatment might be effective. 

PMID- 24909970
TI  - Effect of occlusal rehabilitation on spatial memory and hippocampal neurons after
      long-term loss of molars in rats.
AB  - Experimental loss of occlusal support caused by the extraction or grinding of
      molar teeth has been reported to foment the impairment of learning and memory in
      laboratory animals. The purpose of this study was to examine the effect of
      occlusal reconstruction after long-term loss of molars on spatial memory by using
      8-arm radial maze and by assessing histopathological changes of neuron density in
      the hippocampus. Experimental dentures were inserted into the oral cavities of
      molarless rats to recover the occlusal support. Age-matched groups of control,
      molarless and denture-wearing rats were trained to perform the maze tasks. The
      difference of the error incidence in the maze task was evaluated between three
      groups. The difference of neuron density between three groups was also evaluated
      at the end of the maze task. Serum corticosterone levels were also measured to
      estimate the chronic stress, which could be caused by extraction, insertion of
      the experimental denture or any experimental procedure. The error incidence in
      the denture-wearing group was significantly higher than that of the control
      group, but significantly lower than that of the molarless group. Significant
      differences of neuron density were observed between three groups in each of the
      hippocampal CA1, CA3 and DG subfields. No significant difference of the serum
      corticosterone levels between three groups could be observed. From the results of
      this study, it was suggested that the recovery of occlusal support would bring
      amelioration of cognitive impairment concomitant with long period loss of molars
      in rats. 

PMID- 24909972
TI  - Association between C-reactive protein and depression: modulated by gender and
      mediated by body weight.
AB  - Literature on the relationship between depression and C-reactive protein (CRP), a
      biomarker of systematic inflammation, remains inconsistent. Insufficient
      adjustment for confounders and effect modifiers might be one explanation. We used
      the data of 6396 men and 6610 women aged 18 or older, who completed a depression
      screening and had blood collected as a part of the National Health and Nutrition
      Examination Survey, 2005-2010. Depression was measured using the 9-item
      depression scale of the Patient Health Questionnaire (PHQ-9). The odds ratios
      (ORs) of depression were 1.00 (reference), 1.89 (95% CI=0.77-4.67) and 3.41(1.25
      9.25) respectively for men with low, intermediate and upper quartile of CRP.
      Adjustment for covariates, mainly body mass index, diminished the association
      among women, from 1.65(1.00-2.74) to 1.08(0.57-2.03) for intermediate, from 2.44
      (1.43-4.16) to 1.05 (0.56-1.98) for upper quartile of CRP. Adjustment for the
      history of major medical illnesses changed ORs neither among men nor among women.
      The study concluded that CRP remained significantly associated with depression in
      a dose-response fashion among men but women after being adjusted for body weight.
      Abnormal body weight, both under and overweight, explained a substantial part of
      the relationship between CRP and depression among women. 

PMID- 24909971
TI  - Probing behavioral responses to food: development of a food-specific go/no-go
      task.
AB  - The ability to exert self-control in the face of appetitive, alluring cues is a
      critical component of healthy development. The development of behavioral measures
      that use disease-relevant stimuli can greatly improve our understanding of cue
      specific impairments in self-control. To produce such a tool relevant to the
      study of eating and weight disorders, we modified the traditional go/no-go task
      to include food and non-food targets. To confirm that performance on this new
      task was consistent with other go/no-go tasks, it was given to 147 healthy,
      normal weight volunteers between the ages of 5 and 30. High-resolution photos of
      food or toys were used as the target and nontarget stimuli. Consistent with
      expectations, overall improvements in accuracy were seen from childhood to
      adulthood. Participants responded more quickly and made more commission errors to
      food cues compared to nonfood cues (F(1,140)=21.76, P<0.001), although no
      behavioral differences were seen between low- and high-calorie food cues for this
      non-obese, healthy developmental sample. This novel food-specific go/no-go task
      may be used to track the development of self-control in the context of food cues
      and to evaluate deviations or deficits in the development of this ability in
      individuals at risk for eating problem behaviors and disorders. 

PMID- 24909975
TI  - Chronic recurrent annular neutrophilic dermatosis associated with rheumatoid
      arthritis.

PMID- 24909976
TI  - Normal weight obesity and functional outcomes in older adults.
AB  - BACKGROUND: Obesity defined by body mass index (BMI) is associated with higher
      levels of functional impairment. However, BMI strata misrepresent true adiposity,
      particularly in those with a normal BMI but elevated body fat (BF%) (normal
      weight obesity [NWO]) whom are at higher metabolic and mortality risk. Whether
      this subset of patients is associated with worsening functional outcomes is
      unclear. METHODS: Subjects aged >=60 years with a BMI >=18.5 kg/m(2) from NHANES
      III (1988-1994) were included. We created sex-specific tertiles of BF%. Data on
      physical limitations (PL), instrumental (IADL) and basic activities of daily
      living (BADL) were obtained. The analysis focused on the association between NWO
      and these outcomes. Comparative rates among each tertile using logistic
      regression (referent=lowest tertile) were assessed, incrementally adding co
      variates. RESULTS: Of the 4484 subjects aged >=60 years, 1528 had a normal BMI,
      and the range of the mean age of tertiles was 69.9-71.2 years. Lean mass was
      lowest in the elevated BF% group than in the middle or low tertiles (42.6 vs 44.9
      vs 45.8; p<0.001). Those with NWO had higher PL risk than the referent in females
      only in our adjusted model (males OR 1.18 [0.63-2.21]; females OR 1.90 [1.04
      3.48]) but not after incorporating lean mass (males OR 1.11[0.56-2.20]; females
      (1.73 [0.92-3.25]). Neither sex with high BF% had higher IADL risk than the
      corresponding tertiles (males OR 0.67 [0.35-1.33]; females OR 1.20 [0.74-1.93]).
      NWO was protective in males only (OR 0.28 [0.10-0.83]) but not in females (OR
      0.64 [0.40-1.03]). CONCLUSIONS: NWO is associated with increased physical
      impairment in older adults in females only, highlighting the importance of
      recognizing the association of obesity with disability in elders.

PMID- 24909978
TI  - Endovascular technique for arterial shunting to prevent intraoperative ischemia.
AB  - OBJECTIVES: The use of an intraoperative shunt is an established technique used
      to reduce the ischemic time after acute arterial obstruction or in the prevention
      of hypoperfusion due to complex open vascular or endovascular operative
      procedures. To date, described methods of temporary extremity blood perfusion
      have required open surgical techniques. METHODS: An endovascular shunt (ES) was
      formed by connecting two introducer sheaths to each other, one positioned
      proximal and one distal to an arterial obstruction. The ES method was used in
      patients considered to be at high risk for prolonged lower limb ischemia in
      conjunction with a vascular procedure and where shunt creation by open surgical
      technique was not considered to be a practical alternative. The flow capacity of
      the ES was defined in a desktop model. RESULTS: The ES method was used clinically
      in 15 vascular interventions including eight complex endovascular aortic
      procedures, three open aortic operations, and four procedures for acute limb
      ischemia. The shunts were functional in all patients and there were no shunt
      occlusions. Postoperatively, there were no evident clinical reperfusion injuries.
      Flow analysis revealed that the ES had a flow capacity of 73% flow capacity
      compared to a Pruitt-Inahara shunt. CONCLUSION: A new method of temporary blood
      shunting in connection to vascular procedures has been demonstrated.

PMID- 24909979
TI  - Carotid intima-media thickness and/or carotid plaque: what is relevant?

PMID- 24909973
TI  - The contributions of early adverse experiences and trajectories of respiratory
      sinus arrhythmia on the development of neurobehavioral disinhibition among
      children with prenatal substance exposure.
AB  - Neurobehavioral disinhibition (ND) is a complex condition reflecting a wide range
      of problems involving difficulties with emotion regulation and behavior control.
      Respiratory sinus arrhythmia (RSA) is a physiological correlate of emotion
      regulation that has been studied in a variety of at-risk populations; however,
      there are no studies of RSA in children with ND. Data were drawn from a
      prospective longitudinal study of prenatal substance exposure that included 1,073
      participants. Baseline RSA and RSA reactivity to an attention-demanding task were
      assessed at 3, 4, 5, and 6 years. ND was assessed at ages 8/9, 11, and 13/14
      years via behavioral dysregulation and executive dysfunction composite measures.
      Greater exposure to early adversity was related to less RSA reactivity at 3
      years, increases in RSA reactivity from ages 3 to 6 years, and increased
      behavioral dysregulation from ages 8/9 to 13/14. RSA reactivity was examined as a
      moderator of the association between early adversity and changes in ND. A
      significant Early Adversity * RSA Reactivity quadratic interaction revealed that
      children with decelerations in RSA reactivity exhibited increases in behavioral
      dysregulation, regardless of their exposure to early adversity. However, greater
      exposure to early adversity was related to greater increases in behavioral
      dysregulation, but only if children exhibited accelerations in RSA reactivity
      from ages 3 to 6 years. The results contribute to our understanding of how
      interactions across multiple levels of analysis contribute to the development of
      ND. 

PMID- 24909977
TI  - A histone H3K36 chromatin switch coordinates DNA double-strand break repair
      pathway choice.
AB  - DNA double-strand break (DSB) repair is a highly regulated process performed
      predominantly by non-homologous end joining (NHEJ) or homologous recombination
      (HR) pathways. How these pathways are coordinated in the context of chromatin is
      unclear. Here we uncover a role for histone H3K36 modification in regulating DSB
      repair pathway choice in fission yeast. We find Set2-dependent H3K36 methylation
      reduces chromatin accessibility, reduces resection and promotes NHEJ, while
      antagonistic Gcn5-dependent H3K36 acetylation increases chromatin accessibility,
      increases resection and promotes HR. Accordingly, loss of Set2 increases H3K36Ac,
      chromatin accessibility and resection, while Gcn5 loss results in the opposite
      phenotypes following DSB induction. Further, H3K36 modification is cell cycle
      regulated with Set2-dependent H3K36 methylation peaking in G1 when NHEJ occurs,
      while Gcn5-dependent H3K36 acetylation peaks in S/G2 when HR prevails. These
      findings support an H3K36 chromatin switch in regulating DSB repair pathway
      choice. 

PMID- 24909980
TI  - Inhibition of FASN reduces the synthesis of medium-chain fatty acids in goat
      mammary gland.
AB  - Fatty acid synthase (FASN) is known as a crucial enzyme of cellular de novo fatty
      acid synthesis in mammary gland which has been proved as the main source of short
      and medium-chain fatty acids of milk. However, the regulatory role of FASN in
      goat-specific milk fatty acids composition remains unclear. We cloned and
      analyzed the full-length of FASN gene from the mammary gland of Capra hircus
      (Xinong Saanen dairy goat) (DQ 915966). Comparative gene expression analysis
      suggested that FASN is predominantly expressed in fat, small intestine and
      mammary gland tissues, and expresses higher level at lactation period. Inhibition
      of FASN activity by different concentrations (0, 5, 15, 25 and 35 MUM) of
      orlistat, a natural inhibitor of FASN, resulted in decreased expression of acetyl
      CoA carboxylase alpha (ACCalpha), lipoprotein lipase and heart-type fatty acid
      binding protein (H-FABP) in a concentration-dependent manner in goat mammary
      gland epithelial cells (GMEC). Similar results were also obtained by silencing of
      FASN. Additionally, reduction of FASN expression also led to apparent decline of
      the relative content of decanoic acid (C10:0) and lauric acid (C12:0) in GMEC.
      Our study provides a direct evidence for inhibition of FASN reduces cellular
      medium-chain fatty acids synthesis in GMEC. 

PMID- 24909981
TI  - Montreal Archive of Sleep Studies: an open-access resource for instrument
      benchmarking and exploratory research.
AB  - Manual processing of sleep recordings is extremely time-consuming. Efforts to
      automate this process have shown promising results, but automatic systems are
      generally evaluated on private databases, not allowing accurate cross-validation
      with other systems. In lacking a common benchmark, the relative performances of
      different systems are not compared easily and advances are compromised. To
      address this fundamental methodological impediment to sleep study, we propose an
      open-access database of polysomnographic biosignals. To build this database,
      whole-night recordings from 200 participants [97 males (aged 42.9 +/- 19.8 years)
      and 103 females (aged 38.3 +/- 18.9 years); age range: 18-76 years] were pooled
      from eight different research protocols performed in three different hospital
      based sleep laboratories. All recordings feature a sampling frequency of 256 Hz
      and an electroencephalography (EEG) montage of 4-20 channels plus standard
      electro-oculography (EOG), electromyography (EMG), electrocardiography (ECG) and
      respiratory signals. Access to the database can be obtained through the Montreal
      Archive of Sleep Studies (MASS) website (http://www.ceams-carsm.ca/en/MASS), and
      requires only affiliation with a research institution and prior approval by the
      applicant's local ethical review board. Providing the research community with
      access to this free and open sleep database is expected to facilitate the
      development and cross-validation of sleep analysis automation systems. It is also
      expected that such a shared resource will be a catalyst for cross-centre
      collaborations on difficult topics such as improving inter-rater agreement on
      sleep stage scoring. 

PMID- 24909982
TI  - Safety and prevention of complications during percutaneous epicardial access for
      the ablation of cardiac arrhythmias.

PMID- 24909983
TI  - Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity
      in haemolytic disease of the fetus and newborn.
AB  - Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG
      antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies,
      cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc
      receptors (FcgammaR). Clinical severity is not strictly related to titre and is
      more accurately predicted by the diagnostically-applied monocyte-based antibody
      dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low
      specificity. This suggests that other factors are involved in the pathogenesis of
      HDFN. Binding of IgG to FcgammaR requires the N-linked glycan at position 297 in
      the IgG-Fc-region, consisting of several different glycoforms. We therefore
      systematically analysed IgG-derived glycopeptides by mass spectrometry from 70
      anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women.
      This revealed a variable decrease in Fc-fucosylation in the majority of anti-D
      IgG1 (even down to 12%), whereas the total IgG of these patients remained highly
      fucosylated, like in healthy individuals (>90%). The degree of anti-D
      fucosylation correlated significantly with CD16 (FcgammaRIIIa)-mediated ADCC, in
      agreement with increased affinity of defucosylated IgG to human FcgammaRIIIa.
      Additionally, low anti-D fucosylation correlated significantly with low fetal
      neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG
      fucosylation to be an important pathological feature in HDFN with diagnostic
      potential. 

PMID- 24909984
TI  - Weight-neutral effect of once-daily insulin detemir in Chinese type 2 diabetes
      patients: subgroup analysis of the SOLVE study.
AB  - BACKGROUND: The present subanalysis of the Study of Once Daily Levemir (SOLVE)
      study was to evaluate the safety and efficacy of once-daily insulin detemir as
      add-on to oral antidiabetic drugs (OADs) in Chinese type 2 diabetes patients
      according to body mass index in a real-life setting. METHODS: In all, 3272
      eligible patients who were treated with diet, exercise, and one or more OAD were
      prescribed once-daily insulin detemir by their physician according to routine
      clinical practice and were followed-up for 24 weeks. The incidence of serious
      adverse reactions (SADRs), including major hypoglycemia, was the primary
      endpoint. Subanalyses were performed on patients in the following BMI groups:
      normal weight (BMI < 25 kg/m2); overweight (25 <= BMI < 30 kg/m2); and obese (BMI
      >= 30 kg/m2). RESULTS: No SADRs were reported during the study. Significant
      improvements in glycemic levels were observed in all subgroups. For normal
      weight, overweight, and obese patients, the mean change in HbA1c (%/[mmol/mol])
      was -1.26/-14, -1.09/-12, and -1.06/-12, respectively. The mean change in fasting
      plasma glucose in normal weight, overweight, and obese patients was -2.77, -2.57,
      and -2.71 mmol/L, respectively. Slight weight gain (0.25 kg), slight weight loss
      (-0.36 kg), and weight loss (-1.32 kg) were observed in the normal weight,
      overweight, and obese patients, respectively (P < 0.001). Linear regression
      analysis revealed a negative relationship between weight change and baseline BMI
      (slope = -0.16; P < 0.001). CONCLUSIONS: Once-daily insulin detemir as add-on to
      OADs in Chinese patients with type 2 diabetes showed effective glycemic control
      and a low risk of hypoglycemia. Weight-neutral effects were observed in different
      BMI subgroups.

PMID- 24909986
TI  - Age-associated changes in hippocampal-dependent cognition in Diversity Outbred
      mice.
AB  - Episodic memory impairment due to aging has been linked to hippocampal
      dysfunction. Evidence exists for alterations in specific circuits within the
      hippocampal system that are closely coupled to individual differences in the
      presence and severity of such memory loss. Here, we used the newly developed
      Diversity Outbred (DO) mouse that was designed to model the genetic diversity in
      human populations. Young and aged DO mice were tested in a hippocampal-dependent
      water maze task. Young mice showed higher proficiency and more robust memory
      compared to the overall performance of aged mice. A substantial number of the
      older mice, however, performed on par with the normative performance of the
      younger mice. Stereological quantification of somatostatin-immunoreactive neurons
      in the dentate hilus showed that high-performing young and unimpaired aged mice
      had similar numbers of somatostatin-positive interneurons, while aged mice that
      were impaired in the spatial task had significantly fewer such neurons. These
      data in the DO model tie loss of hilar inhibitory network integrity to age
      related memory impairment, paralleling data in other rodent models.

PMID- 24909985
TI  - B cells regulate macrophage phenotype and response to chemotherapy in squamous
      carcinomas.
AB  - B cells foster squamous cell carcinoma (SCC) development through deposition of
      immunoglobulin-containing immune complexes in premalignant tissue and Fcgamma
      receptor-dependent activation of myeloid cells. Because human SCCs of the vulva
      and head and neck exhibited hallmarks of B cell infiltration, we examined B cell
      deficient mice and found reduced support for SCC growth. Although ineffective as
      a single agent, treatment of mice bearing preexisting SCCs with B cell-depleting
      alphaCD20 monoclonal antibodies improved response to platinum- and Taxol-based
      chemotherapy. Improved chemoresponsiveness was dependent on altered chemokine
      expression by macrophages that promoted tumor infiltration of activated CD8(+)
      lymphocytes via CCR5-dependent mechanisms. These data reveal that B cells, and
      the downstream myeloid-based pathways they regulate, represent tractable targets
      for anticancer therapy in select tumors. 

PMID- 24909988
TI  - Feasibility of intracoronary frequency domain optical coherence tomography
      derived fractional flow reserve for the assessment of coronary artery stenosis.
AB  - Frequency domain optical coherence tomography (FD-OCT) provides cross-sectional
      images of coronary arteries and deployed stents with micron resolution and
      measures lumen dimensions with excellent reproducibility. FD-OCT combined with a
      blood flow resistances model can overcome many limitations of conventional
      measures of stenosis severity based on quantitative coronary angiography (QCA)
      and intravascular ultrasound (IVUS). The aim of this feasibility study was to
      investigate the relationship between pressure derived fractional flow reserve
      (FFR) and FD-OCT derived FFR, a new method for quantitative measure of stenosis
      severity that estimates the blood flow resistance and microvascular resistance of
      the vessel segments imaged by FD-OCT. A total of 26 coronary stenoses in 20
      patients were studied consecutively with QCA, pressure derived FFR, and FD-OCT.
      There was a moderate but significant correlation between pressure derived FFR and
      FD-OCT derived FFR (r = 0.69, P < 0.001). Bland-Altman analysis showed that the
      mean differences between pressure derived FFR and FD-OCT derived FFR were 0.05 +/
      0.14 (limits of agreement: -0.09 to 0.19). The root mean square error (RMSE)
      between FD-OCT derived FFR and pressure derived FFR was found to be +/- 0.087 FFR
      units. FD-OCT derived FFR has the potential to become a valuable tool for the
      assessment of coronary artery stenosis. 

PMID- 24909987
TI  - Early physiological regulation predicts the trajectory of externalizing behaviors
      across the preschool period.
AB  - Early assessments of children's physiological functioning are shown to predict
      subsequent developmental outcomes. However, individual changes that occur in the
      development of physiological systems may be associated with the pattern of change
      in behavior across time. Thus, we examined change in respiratory sinus arrhythmia
      (RSA), an index of physiological regulation, as a time-varying predictor in order
      to assess whether RSA change at ages 3, 4, and 5 uniquely influenced the
      trajectory of externalizing behaviors from age 3 to 5. Results indicated that
      only at age 3 was RSA change significantly associated with decreases in
      externalizing behaviors over time. RSA change scores at ages 4 and 5 were
      unrelated to trajectories of externalizing behavior, suggesting that the ability
      to physiologically regulate by age 3 may contribute to the development of skills
      that facilitate more control over behavior throughout preschool, and therefore
      may be more strongly associated with the pattern of change in externalizing
      behaviors than later physiological regulation.

PMID- 24909989
TI  - Paediatric drug policy in Australia.

PMID- 24909990
TI  - Crystal structure of a human GABAA receptor.
AB  - Type-A gamma-aminobutyric acid receptors (GABAARs) are the principal mediators of
      rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR
      signalling triggers hyperactive neurological disorders such as insomnia, anxiety
      and epilepsy. Here we present the first three-dimensional structure of a GABAAR,
      the human beta3 homopentamer, at 3 A resolution. This structure reveals
      architectural elements unique to eukaryotic Cys-loop receptors, explains the
      mechanistic consequences of multiple human disease mutations and shows an
      unexpected structural role for a conserved N-linked glycan. The receptor was
      crystallized bound to a previously unknown agonist, benzamidine, opening a new
      avenue for the rational design of GABAAR modulators. The channel region forms a
      closed gate at the base of the pore, representative of a desensitized state.
      These results offer new insights into the signalling mechanisms of pentameric
      ligand-gated ion channels and enhance current understanding of GABAergic
      neurotransmission. 

PMID- 24909991
TI  - Genetics of ecological divergence during speciation.
AB  - Ecological differences often evolve early in speciation as divergent natural
      selection drives adaptation to distinct ecological niches, leading ultimately to
      reproductive isolation. Although this process is a major generator of
      biodiversity, its genetic basis is still poorly understood. Here we investigate
      the genetic architecture of niche differentiation in a sympatric species pair of
      threespine stickleback fish by mapping the environment-dependent effects of
      phenotypic traits on hybrid feeding and performance under semi-natural
      conditions. We show that multiple, unlinked loci act largely additively to
      determine position along the major niche axis separating these recently diverged
      species. We also find that functional mismatch between phenotypic traits reduces
      the growth of some stickleback hybrids beyond that expected from an intermediate
      phenotype, suggesting a role for epistasis between the underlying genes. This
      functional mismatch might lead to hybrid incompatibilities that are analogous to
      those underlying intrinsic reproductive isolation but depend on the ecological
      context. 

PMID- 24909992
TI  - Horizontal genome transfer as an asexual path to the formation of new species.
AB  - Allopolyploidization, the combination of the genomes from two different species,
      has been a major source of evolutionary innovation and a driver of speciation and
      environmental adaptation. In plants, it has also contributed greatly to crop
      domestication, as the superior properties of many modern crop plants were
      conferred by ancient allopolyploidization events. It is generally thought that
      allopolyploidization occurred through hybridization events between species,
      accompanied or followed by genome duplication. Although many allopolyploids arose
      from closely related species (congeners), there are also allopolyploid species
      that were formed from more distantly related progenitor species belonging to
      different genera or even different tribes. Here we have examined the possibility
      that allopolyploidization can also occur by asexual mechanisms. We show that upon
      grafting--a mechanism of plant-plant interaction that is widespread in nature-
      entire nuclear genomes can be transferred between plant cells. We provide direct
      evidence for this process resulting in speciation by creating a new allopolyploid
      plant species from a herbaceous species and a woody species in the nightshade
      family. The new species is fertile and produces fertile progeny. Our data
      highlight natural grafting as a potential asexual mechanism of speciation and
      also provide a method for the generation of novel allopolyploid crop species.

PMID- 24909995
TI  - Editorial comment on "Urinary bladder cancer treated with radical cystectomy:
      perioperative parameters and early complications prospectively registered in a
      national population-based database".

PMID- 24909993
TI  - The structural basis of transfer RNA mimicry and conformational plasticity by a
      viral RNA.
AB  - RNA is arguably the most functionally diverse biological macromolecule. In some
      cases a single discrete RNA sequence performs multiple roles, and this can be
      conferred by a complex three-dimensional structure. Such multifunctionality can
      also be driven or enhanced by the ability of a given RNA to assume different
      conformational (and therefore functional) states. Despite its biological
      importance, a detailed structural understanding of the paradigm of RNA structure
      driven multifunctionality is lacking. To address this gap it is useful to study
      examples from single-stranded positive-sense RNA viruses, a prototype being the
      tRNA-like structure (TLS) found at the 3' end of the turnip yellow mosaic virus
      (TYMV). This TLS not only acts like a tRNA to drive aminoacylation of the viral
      genomic (g)RNA, but also interacts with other structures in the 3' untranslated
      region of the gRNA, contains the promoter for negative-strand synthesis, and
      influences several infection-critical processes. TLS RNA can provide a glimpse
      into the structural basis of RNA multifunctionality and plasticity, but for
      decades its high-resolution structure has remained elusive. Here we present the
      crystal structure of the complete TYMV TLS to 2.0 A resolution. Globally, the RNA
      adopts a shape that mimics tRNA, but it uses a very different set of
      intramolecular interactions to achieve this shape. These interactions also allow
      the TLS to readily switch conformations. In addition, the TLS structure is 'two
      faced': one face closely mimics tRNA and drives aminoacylation, the other face
      diverges from tRNA and enables additional functionality. The TLS is thus
      structured to perform several functions and interact with diverse binding
      partners, and we demonstrate its ability to specifically bind to ribosomes. 

PMID- 24909996
TI  - Combined laser acupuncture and desmopressin for treating resistant cases of
      monosymptomatic nocturnal enuresis: a randomized comparative study.
AB  - OBJECTIVE: Monosymptomatic nocturnal enuresis (MNE) is a common sociomedical
      problem affecting children that may persist until adulthood despite various lines
      of therapy. The aim of this study was to assess the efficacy of combined laser
      acupuncture and desmopressin in managing patients with resistant MNE, compared
      with their efficacy when used as monotherapy. MATERIAL AND METHODS: The study
      included 186 patients with a mean age of 15.7 years (range 10-21 years)
      presenting with persistent MNE. All patients were evaluated clinically and
      investigated with urine analysis, plain X-ray of the urinary tract and abdominal
      ultrasonography. They were randomized into three equal groups based on the line
      of management: group A, managed with laser acupuncture alone; group B, managed
      with desmopressin alone; and group C, managed with a combination of laser
      acupuncture and desmopressin, with a treatment course of 3 months and follow-up
      period of 6 months to record the efficacy of therapy, side-effects and bladder
      capacity. RESULTS: A statistically significant higher cure rate was reported in
      group C patients, being reported in 33, 35 and 46 patients in groups A, B and C,
      respectively. Improvement was reported in 18, 17 and 13 cases in groups A, B and
      C, respectively, but the difference was not statistically significant. Bladder
      capacity significantly increased only in patients receiving acupuncture (groups A
      and C). CONCLUSION: Combined laser acupuncture and desmopressin is a promising
      and valid option to manage resistant cases of MNE.

PMID- 24909994
TI  - SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell
      carcinoma.
AB  - Cancer stem cells (CSCs) have been reported in various cancers, including in skin
      squamous-cell carcinoma (SCC). The molecular mechanisms regulating tumour
      initiation and stemness are still poorly characterized. Here we find that Sox2, a
      transcription factor expressed in various types of embryonic and adult stem
      cells, was the most upregulated transcription factor in the CSCs of squamous skin
      tumours in mice. SOX2 is absent in normal epidermis but begins to be expressed in
      the vast majority of mouse and human pre-neoplastic skin tumours, and continues
      to be expressed in a heterogeneous manner in invasive mouse and human SCCs. In
      contrast to other SCCs, in which SOX2 is frequently genetically amplified, the
      expression of SOX2 in mouse and human skin SCCs is transcriptionally regulated.
      Conditional deletion of Sox2 in the mouse epidermis markedly decreases skin
      tumour formation after chemical-induced carcinogenesis. Using green fluorescent
      protein (GFP) as a reporter of Sox2 transcriptional expression (SOX2-GFP knock-in
      mice), we showed that SOX2-expressing cells in invasive SCC are greatly enriched
      in tumour-propagating cells, which further increase upon serial transplantations.
      Lineage ablation of SOX2-expressing cells within primary benign and malignant
      SCCs leads to tumour regression, consistent with the critical role of SOX2
      expressing cells in tumour maintenance. Conditional Sox2 deletion in pre-existing
      skin papilloma and SCC leads to tumour regression and decreases the ability of
      cancer cells to be propagated upon transplantation into immunodeficient mice,
      supporting the essential role of SOX2 in regulating CSC functions.
      Transcriptional profiling of SOX2-GFP-expressing CSCs and of tumour epithelial
      cells upon Sox2 deletion uncovered a gene network regulated by SOX2 in primary
      tumour cells in vivo. Chromatin immunoprecipitation identified several direct
      SOX2 target genes controlling tumour stemness, survival, proliferation, adhesion,
      invasion and paraneoplastic syndrome. We demonstrate that SOX2, by marking and
      regulating the functions of skin tumour-initiating cells and CSCs, establishes a
      continuum between tumour initiation and progression in primary skin tumours. 

PMID- 24909997
TI  - Autoimmunity and inflammation in X-linked agammaglobulinemia.
AB  - PURPOSE: In the past, XLA was described as associated with several inflammatory
      conditions, but with adequate immune globulin treatment, these are presumed to
      have diminished. The actual prevalence is not known. METHODS: A web-based patient
      survey was conducted December 2011- February 2012. Respondents were recruited
      from the Immune Deficiency Foundation (IDF) patient database, online patient
      discussion forums and physician recruitment of patients. The questionnaire was
      developed jointly by IDF and by members of the USIDNET-XLA Disease Specific
      Working Group. Information regarding inflammatory conditions in patients with XLA
      was also obtained from the United States Immune Deficiency Network (USIDNET)
      Registry. RESULTS: Based on 128 unique patient survey responses, the majority of
      respondents (69%) reported having at least one inflammatory symptom, with 53%
      reporting multiple symptoms. However, only 28% had actually been formally
      diagnosed with an inflammatory condition. Although 20% reported painful joints
      and 11% reported swelling of the joints, only 7% were given a diagnosis of
      arthritis. Similarly, 21% reported symptoms of chronic diarrhea and 17% reported
      abdominal pain, however only 4% had been diagnosed with Crohn's disease. Data
      from the USIDNET Registry on 149 patients with XLA, revealed that 12% had pain,
      swelling or arthralgias, while 18% had been diagnosed with arthritis. Similarly,
      7% of these patients had abdominal pain and 9% chronic diarrhea. CONCLUSIONS:
      Although patients with XLA are generally considered to have a low risk of
      autoimmune or inflammatory disease compared to other PIDD cohorts, data from this
      patient survey and a national registry indicate that a significant proportion of
      patients with XLA have symptoms that are consistent with a diagnosis of
      arthritis, inflammatory bowel disease or other inflammatory condition. Documented
      diagnoses of inflammatory diseases were less common but still increased over the
      general population. Additional data is required to begin implementation of
      careful monitoring of patients with XLA for these conditions. Early diagnosis and
      proper treatment may optimize clinical outcomes for these patients.

PMID- 24909998
TI  - A justification for less restrictive guidelines on the use of metformin in stable
      chronic renal failure.
AB  - AIM: The aim was to justify less restrictive use of metformin in stable chronic
      renal failure, because a literature review reveals metformin is associated with a
      significantly lower incidence of cardiovascular events and mortality compared
      with other hypoglycaemic agents, and metformin-associated lactic acidosis is rare
      and causation uncertain. Studies on intentional metformin overdose and metformin
      bioavailability, renal clearance and plasma metformin in renal impairment provide
      evidence in support of a less restrictive use of metformin. METHODS: In metformin
      overdose (n = 22), lactic acidosis was not inevitable with a plasma metformin >
      40 mg/l (therapeutic level c. 1 mg/l): Severe lactic acidosis (pH <= 7.21, plasma
      lactate >= 11 mmol/l, n = 8) did not occur unless plasma metformin was > 40 mg/l.
      Plasma lactate was a more consistent predictor of pH than plasma metformin, with
      plasma lactate <= 4.7 being associated with a pH >= 7.34. A likely 'safe' plasma
      lactate is < 3.5 mmol/l and plasma metformin < 10 mg/l. RESULTS: Plasma metformin
      can be predicted from estimated glomerular filtration rate and metformin dose.
      Reported plasma metformin in renal failure was always less than predicted plasma
      metformin. Predicted plasma metformin (mg/l), with an estimated glomerular
      filtration rate of 30 ml/min and metformin 2000 mg/day was 6.8; an estimated
      glomerular filtration rate of 20 ml/min and metformin 1500 mg/day was 5.1; an
      estimated glomerular filtration rate of 10 ml/min and metformin 500 mg/day was
      4.4. CONCLUSION: Metformin accumulates in renal failure and, although
      accumulation does not always lead to lactic acidosis, dose modification to
      achieve a predicted plasma metformin < 10 mg/l is suggested. As plasma metformin
      is not routinely available, plasma lactate should be useful in monitoring the use
      of metformin in renal failure.

PMID- 24909999
TI  - Inhibitory effect of a novel combination of Salvia hispanica (chia) seed and
      Punica granatum (pomegranate) fruit extracts on melanin production.
AB  - In recent years, dietary fatty acids have been extensively evaluated for
      nutritional as well as cosmetic benefits. Among the dietary fats, the omega-3
      (omega3) and omega-6 (omega6) forms of polyunsaturated fatty acids (PUFAs) have
      been found to exhibit many biological functions in the skin such as prevention of
      transepidermal water loss, maintenance of the stratum corneum epidermal barrier,
      and disruption of melanogenesis in epidermal melanocytes. In this study, we
      examined the effect of chia seed extract, high in omega3 (linolenic acid) and
      omega6 (linoleic acid) PUFAs, for its capacity to affect melanogenesis. Chia seed
      extract was shown to inhibit melanin biosynthesis in Melan-a cells; however,
      linoleic and alpha-linolenic acids alone did not effectively reduce melanin
      content. Further investigation demonstrated that chia seed extract in combination
      with pomegranate fruit extract had a synergistic effect on the inhibition of
      melanin biosynthesis with no corresponding effect on tyrosinase activity.
      Investigation of the possible mechanism of action revealed that chia seed extract
      downregulated expression of melanogenesis-related genes (Tyr, Tyrp1, and Mc1r),
      alone and in combination with pomegranate fruit extract, suggesting that the
      inhibition of melanin biosynthesis by a novel combination of chia seed and
      pomegranate fruit extracts is possibly due to the downregulation of gene
      expression of key melanogenic enzymes. 

PMID- 24910001
TI  - Triterpene saponins from the roots of Ilex pubescens.
AB  - Five new triterpene saponins, Ilexpublesnins N-R (1-5), along with seven known
      analogs were isolated from the root of Ilex pubescens. Their structures were
      elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D
      NMR experiments. Ilexpublesnin N (1) possessed a rare 20-hydroxyursolic acid
      scaffold from natural resource. These compounds were evaluated in vitro for their
      cytotoxic effects on human cancer cell lines HepG2, HLE, BEL7402, BEL7403,
      BEL7405, MCF-7, HeLa. Among them, only compounds 5 and 10 showed cytotoxic
      potentiality against BEl-7403 and HEL cell lines [inhibition (%): 35.38 and
      45.12, respectively]. 

PMID- 24910000
TI  - Urinary metabolites of isorhynchophylline in rats and their neuroprotective
      activities in the HT22 cell assay.
AB  - Isorhynchophylline is one of the major alkaloids from the Uncaria hook possessing
      the effects of lowered blood pressure, vasodilatation and protection against
      ischemia-induced neuronal damage. However, the metabolic pathway of
      isorhynchophylline has not been fully reported yet. In this paper, the metabolism
      of isorhynchophylline was investigated in rats. Five metabolites were isolated by
      using solvent extraction and repeated chromatographic methods, and identified by
      spectroscopic methods including UV, MS, NMR and CD experiments. Three new
      compounds were identified as 5-oxoisorhynchophyllic acid-22-O-beta-D-glucuronide
      (M1), 17-O-demethyl-16,17-dihydro isorhynchophylline (M2) and 5
      oxoisorhynchophyllic acid (M4) together with two known compounds
      isorhynchophylline (M0) and rhynchophylline (M3). Possible metabolic pathways of
      isorhynchophylline are proposed. Furthermore, the activity assay for all the
      metabolites showed that isorhynchophylline (M0) exhibited potent neuroprotective
      effects against glutamate-induced HT22 cell death. However, little or weak
      neuroprotective activities were observed for M1-M4. Our present study is
      important to further understand its metabolic fate and disposition in humans. 

PMID- 24910002
TI  - Identification and distribution of four metabolites of geniposide in rats with
      adjuvant arthritis.
AB  - Geniposide (GE), also called Jasminoidin, is the major active ingredient of
      Gardenia jasminoides Ellis (GJ) fruit, which has long been used in traditional
      Chinese medicine (TCM). Growing evidences suggested that GE has a great
      potentiality for treating rheumatoid arthritis (RA). However, GE is rapidly
      metabolized, and we know little about its availability or metabolites in tissues.
      To elucidate the distribution of GE and its metabolites in tissues, three groups
      of adjuvant arthritis (AA) rats were given GE (33, 66 and 120 mg/kg) from days 18
      to 24, and the biotransformation of GE in plasma, liver, spleen, synovium, urine
      and mesenteric lymph node (MLN) of rats was investigated by a novel approach
      named Information-Dependent Acquisition (IDA)-Mediated LC-MS/MS method. As a
      result, GE and its four major metabolites were detected as follows: GE, G1, G2 in
      plasma; GE, G2 in MLNs; only GE in liver and synovium; GE, G2, G3 and G4 in
      spleen; and GE, G1, G2 and G4 in urine. In total four metabolites (G1-G4)
      involved in the in vivo metabolism processes were identified. The results of this
      work have demonstrated the IDA-Mediated LC-MS/MS could screen rapidly and
      reliably the characterization of metabolites from iridoid compounds.

PMID- 24910003
TI  - Naive tumour-specific CD4+ T cells were efficiently primed in acute lymphoblastic
      leukaemia.
AB  - The recognition and neutralization of tumour cells is one of the big challenges
      in immunity. The immune system has to recognize syngeneic tumour cells and has to
      be primed and respond in an adequate manner. Priming of a leukaemia-specific
      immune response is a crucial step in tumour immunology that can mislead to tumour
      tolerance either by T cell ignorance, deletion or Treg induction. To resemble the
      situation of acute lymphoblastic leukaemia (ALL) in patients, we used the murine
      BALB/c model with syngeneic BM185 tumour cells. We established a tumour cell line
      that expresses the neo-antigen ovalbumin (BM185-OVA/GFP) to allow the application
      of T cell receptor transgenic, antigen-specific CD4(+) T cells. Here, we
      demonstrate that effective anti-ALL immunity can be established by in vivo
      priming of CD4(+) T cells that is sufficient to differentiate into effector
      cells. Yet they failed to control tumour alone, but initiated a Th1 response. An
      efficient tumour clearance was dependent on both antigen-specific CD4(+) T cells
      and CD8(+) effector T cells from the endogenous repertoire. The tolerogeneic
      milieu was characterized by increased Tregs numbers and elevated IL-10 level.
      Tregs hamper effective antitumour immune response, but their depletion did not
      result in reduced tumour growth. In contrast, neutralization of IL-10 improved
      median mouse survival. Future therapies should focus on establishing a strong
      CD4+ T cells response, either by adjuvant or by adoptive transfer. 

PMID- 24910004
TI  - Iron porphyrin carbenes as catalytic intermediates: structures, Mossbauer and NMR
      spectroscopic properties, and bonding.
AB  - Iron porphyrin carbenes (IPCs) are thought to be intermediates involved in the
      metabolism of various xenobiotics by cytochrome P450, as well as in chemical
      reactions catalyzed by metalloporphyrins and engineered P450s. While early work
      proposed IPCs to contain Fe(II), more recent work invokes a double-bond
      description of the iron-carbon bond, similar to that found in Fe(IV) porphyrin
      oxenes. Reported herein is the first quantum chemical investigation of IPC
      Mossbauer and NMR spectroscopic properties, as well as their electronic
      structures, together with comparisons to ferrous heme proteins and an Fe(IV)
      oxene model. The results provide the first accurate predictions of the
      experimental spectroscopic observables as well as the first theoretical
      explanation of their electrophilic nature, as deduced from experiment. The
      preferred resonance structure is Fe(II)<-{:C(X)Y}(0) and not Fe(IV)={C(X)Y}(2-),
      a result that will facilitate research on IPC reactivities in various chemical
      and biochemical systems.

PMID- 24910005
TI  - Understanding the sources of normative influence on behavior: the example of
      tobacco.
AB  - Despite extensive research on social norms, the sources of norm formation are not
      well understood. Social exposure to a behavior (defined as the composite of ways
      through which people see that behavior in their social, physical, and symbolic
      environments) can serve as a source of normative influence. Using tobacco as a
      case study, we propose that research should move beyond categories of individuals
      as sources of norms and focus on a broader range of sources of normative
      influences. An understanding of social exposure as a source for norms may be
      important to better understand and intervene in environments to promote public
      health. We make policy recommendations arising from the explication of social
      exposure and propose directions for future research. 

PMID- 24910006
TI  - Effect of nitric oxide on MU-calpain activation, protein proteolysis, and protein
      oxidation of pork during post-mortem aging.
AB  - The aim of the current research was to examine the influence of nitric oxide (NO)
      on calpain activation, protein proteolysis, and oxidation in post-mortem pork.
      Five longissimus muscles were removed from carcass after slaughter, and samples
      were incubated with water, nitric oxide synthase (NOS) inhibitor, or NO donor for
      24 h at 4  degrees C. The samples were taken out and then stored under 4  degrees
      C for 1, 4, and 7 d. Results showed that autolysis of MU-calpain increased by
      incubation with NOS inhibitor after storage for 1 d (P<0.05). Degradation of
      titin and nebulin increased by treatment of NOS inhibitor among three treatments
      (P<0.05). Higher levels of protein oxidation were observed after samples
      incubated with NO donor than treatment of NOS inhibitor (P<0.05). These data
      indicated that NO could participate in regulating calpain activation and its
      proteolysis activity during post-mortem aging.

PMID- 24910007
TI  - Revenge and psychological adjustment after homicidal loss.
AB  - Feelings of revenge are a common human response to being hurt by others. Among
      crime victims of severe sexual or physical violence, significant correlations
      have been reported between revenge and Posttraumatic Stress Disorder (PTSD).
      Homicide is one of the most severe forms of interpersonal violence. It is
      therefore likely that individuals bereaved by homicide experience high levels of
      revenge, which may hamper efforts to cope with traumatic loss. The relationship
      between revenge and psychological adjustment following homicidal loss has not yet
      been empirically examined. In the current cross-sectional study, we used self
      report data from 331 spouses, family members and friends of homicide victims to
      examine the relationships between dispositional revenge and situational revenge
      on the one hand and symptom-levels of PTSD and complicated grief, as well as
      indices of positive functioning, on the other hand. Furthermore, the association
      between revenge and socio-demographic and offense-related factors was examined.
      Participants were recruited from a governmental support organization, a website
      with information for homicidally bereaved individuals, and members of support
      groups. Levels of both dispositional and situational revenge were positively
      associated with symptoms of PTSD and complicated grief, and negatively with
      positive functioning. Participants reported significantly less situational
      revenge in cases where the perpetrator was a direct family member than cases
      where the perpetrator was an indirect family member, friend, or someone unknown.
      Homicidally bereaved individuals reported more situational revenge, but not more
      dispositional revenge than a sample of students who had experienced relatively
      mild interpersonal transgressions.

PMID- 24910009
TI  - Stress analysis of zirconia studied by Raman spectroscopy at low temperatures.
AB  - The paper presents effect of low temperature upon location of selected Raman
      bands. The structural properties of pure zirconium pre-oxidized at 773K and 873K
      have been studied during cooling in the range of temperatures 273K and 93K by
      Raman spectroscopy. Analysis of the Raman band positions for the monoclinic phase
      of zirconia oxide was performed. Raman spectroscopy has shown that monoclinic
      phase of zirconia oxide undergoes a continuous band displacement, individual for
      each studied Raman mode. Registered shift is aimed towards the high frequency
      direction. Recorded Raman band displacement was employed to study stress state in
      zirconia oxide films grown on pure zirconium developed during control cooling.
      Presented results showed a good correlation between different thicknesses of the
      oxide scale. 

PMID- 24910008
TI  - Mannose-binding lectin exon 1 and promoter polymorphisms in tuberculosis disease
      in a Mediterranean area.
AB  - Mannose-binding lectin (MBL) is a serum protein that activates the complement and
      mediates phagocytosis. MBL levels and MBL2 genotype may impact upon host
      susceptibility to tuberculosis (TB) disease but evidence to date has been
      conflicting. MBL2 exon 1 and promoter genotyping and serum MBL concentrations
      were determined in 79 patients with active tuberculosis (58 pulmonary TB and 21
      extrapulmonary or miliary TB) and 120 household healthy contacts (HHC) from a
      Mediterranean area (Majorca Island, Spain). Significantly higher serum MBL levels
      were found in patients with active tuberculosis than in HHC [median MBL
      concentrations 3430 ng mL(-1) (10-28 415) and 2600 ng mL(-1) (5-20 000)
      respectively, P = 0.002]. These higher MBL levels were mainly related to the most
      prevalent YA/YA wild-type diplotype. There was a strong correlation between MBL2
      exon 1 and promoter genotype and MBL levels. The diplotype LYQA/HYPA was present
      in 12 out of 57 of the pulmonary TB cases but in none of the extrapulmonary TB
      patients. Diplotype LXPA/HYPA, producer of high levels of MBL, was significantly
      more frequent in HHC than in patients (16.8% vs. 6.4%, P = 0.031) suggesting a
      protective role against the development of TB disease that has not been
      previously found.

PMID- 24910011
TI  - Nanobiotechnology-based drug delivery in brain targeting.
AB  - Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery
      to brain in combating the central nervous system (CNS) disorders. Such limiting
      physiological factors include the reticuloendothelial system and protein
      opsonization, which present across BBB, play major role in reducing the passage
      of drug. Several approaches employed to improve the drug delivery across the BBB.
      Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in
      size utilized as career for drug delivery. At present NPs are found to play a
      significant advantage over the other methods of available drug delivery systems
      to deliver the drug across the BBB. Nanoparticles may be because of its size and
      functionalization characteristics able to penetrate and facilitate the drug
      delivery through the barrier. There are number of mechanisms and strategies found
      to be involved in this process, which are based on the type of nanomaterials used
      and its combination with therapeutic agents, such materials include liposomes,
      polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy,
      etc. Nanotechnology is expected to reduce the need for invasive procedures for
      delivery of therapeutics to the CNS. Some devices such as implanted catheters and
      reservoirs however will still be needed to overcome the problems in effective
      drug delivery to the CNS. Nanomaterials are found to improve the safety and
      efficacy level of drug delivery devices in brain targeting. Nanoegineered devices
      are found to be delivering the drugs at cellular levels through nono-fluidic
      channels. Different drug delivery systems such as liposomes, microspheres,
      nanoparticles, nonogels and nonobiocapsules have been used to improve the
      bioavailability of the drug in the brain, but microchips and biodegradable
      polymeric nanoparticulate careers are found to be more effective therapeutically
      in treating brain tumor. The physiological approaches also utilized to improve
      the transcytosis capacity of specific receptors expressed across the BBB. It is
      found that the low density lipoproteins related protein (LPR) with engineered
      peptide compound (EpiC) formed the platform incorporating the Angiopep peptide as
      a new effective therapeutics. The current challenges are to design and develop
      the drug delivery careers, which must be able to deliver the drug across the BBB
      at a safe and effective manner. Nanoparticles are found to be effective careers
      in delivery of conventional drugs, recombinant proteins, vaccines as well as
      nucleotides. Nanoparticlulate drug delivery systems are found to be improving in
      the pharmacokinetic strategies of the drug molecules such as biodistribution,
      bioavailability and drug release characteristics in a controlled and effective
      manner with site specific drug delivery targeting to tissue or cell with
      reduction in toxic manifestation. Therefore, the use of nanotechnology in the
      field of pharmaceutical biotechnology helps in improving the drug delivery
      strategy including the kinetics and therapeutic index to solve the delivery
      problems of some biotech drugs including the recombinant proteins and
      oligonucleotides. This review is made to provide an insight to the role of
      nanobiotechnology in drug delivery and drug targeting to brain and its recent
      advances in the field of drug delivery systems.

PMID- 24910010
TI  - A cryospectroscopic infrared and Raman study of the CX?pi halogen bonding motif:
      complexes of the CF3Cl, CF3Br, and CF3I with ethyne, propyne and 2-butyne.
AB  - Experimental information on the C-X?pi halogen bonding motif was obtained by
      studying the formation of molecular complexes of CF3Cl, CF3Br and CF3I with
      ethyne, propyne and 2-butyne in liquid krypton, using FTIR and Raman
      spectroscopy. For CF3Br, experimental evidence was found for the formation of 1:1
      complexes with propyne and 2-butyne only, while for CF3I spectroscopic features
      confirming the existence of the halogen bonded complexes were observed for
      ethyne, propyne and 2-butyne. In addition, at higher concentrations of CF3I and 2
      butyne, weak absorptions due to a 2:1 complex were also observed. The
      experimental complexation enthalpies, obtained by using spectra recorded at
      temperatures between 120 K and 140 K, are -5.9(3) kJ mol(-1) for CF3I.ethyne, 
      5.6(3) kJ mol(-1) for CF3Br.propyne, -8.1(2) kJ mol(-1) for CF3I.propyne, -7.3(2)
      kJ mol(-1) for CF3Br.2-butyne, -10.9(2) kJ mol(-1) for CF3I.2-butyne and -20.9(7)
      kJ mol(-1) for (CF3I)2.2-butyne. The experimental study is supported by
      theoretical data obtained from ab initio calculations at the MP2/aug-cc-pVDZ(-PP)
      and MP2/aug-cc-pVTZ(-PP) levels, and Monte Carlo Free Energy Perturbation (MC
      FEP) simulations. The experimental and theoretical values on the C-X?pi halogen
      bonding motifs studied are compared with previously reported data for the
      complexes with ethene and propene and with preliminary results obtained for
      benzene and toluene.

PMID- 24910012
TI  - Potentials and challenges of active targeting at the tumor cells by engineered
      polymeric nanoparticles.
AB  - Tumor targeted therapy has brought a new hope to the cancer patients. With the
      recent advances in nanotechnology and growing knowledge on unique cancer
      biomarkers, it is now possible to manipulate the surface architecture of
      polymeric nanoscale delivery systems with targeting moieties, such as antibodies,
      antibody fragments, specific molecules, small peptides, RNA aptamers etc. to
      target specific receptors and antigens present exclusively or overexpressed on
      the tumor cell surface or on the tumor endothelial cell surface. These modified
      polymeric nanoparticles deliver the loaded chemotherapeutics preferentially to
      the tumor tissue and not to the healthy tissue. This ensures highly targeted
      treatment without severe side effects which are normally experienced by the
      cancer patients in case of conventional chemotherapy. Such specifically
      constructed polymeric nanocarriers with improved tumor targeting profile are now
      regarded as engineered polymeric nanoparticles, which have become one of the
      prime areas of drug delivery research in recent times. This review describes
      specific approaches used in recent years to construct engineered polymeric
      nanoparticles, their emerging potential for cancer therapy and recent advances in
      tumor targeting. An equal attention has been devoted to the fundamental problems
      encountered in practical fields which limit their clinical use and industrial
      production. 

PMID- 24910013
TI  - Insight into structural organization and protein-protein interaction of non
      structural 3 (NS3) proteins from dengue serotypes.
AB  - Dengue infections produce a distinct character of virus-induced intracellular
      membrane alterations which are associated with the viral replication machinery.
      Currently, the NS3 protein is being targeted for antiviral therapy against
      dengue. NS3 protein of dengue virus interacts with nuclear receptor binding
      protein (NRBP) of human causing cell trafficking between the Endoplasmic
      Reticulum (ER) and Golgi, which interacts with Rac3, a member of the Rho-GTPase
      family. No crystal structure of the NRBP is available for any species, thus
      limiting the complete understanding of structure- function relationships of this
      protein. The present study deals with the molecular modeling of the viral protein
      (NS3 of DENV1-4), the host protein (NRBP) and their interactions through protein
      protein docking study. Theoretical threedimensional structures of the NRBP and
      NS3 were modeled using the Modeller 9v8, and the evaluated models were docked
      using GRAMM-X to study the mode of protein-protein interaction (NRBP as receptor
      and NS3 as ligand). The docked docking complexes were further evaluated for
      interaction analysis by the RosettaDock Server. Suface and interface residues
      were observed along with hydrogen and hydrophobic interaction. The conserved
      residues forming hydrogen interaction of NRBP with DENV1-4 serotypes were found
      to be GLN 305, SER 363 and GLN 379. 

PMID- 24910014
TI  - Linking host prokaryotic physiology to viral lifestyle dynamics in a temperate
      freshwater lake (Lake Pavin, France).
AB  - In aquatic ecosystems, fluctuations in environmental conditions and prokaryotic
      host physiological states can strongly affect the dynamics of viral life
      strategies. The influence of prokaryote physiology and environmental factors on
      viral replication cycles (lytic and lysogeny) was investigated from April to
      September 2011 at three different strata (epi, meta, and hypolimnion) in the
      mixolimnion of deep volcanic temperate freshwater Lake Pavin (France). Overall,
      the euphotic region (epi and metalimnion) was more dynamic and showed significant
      variation in microbial standing stocks, prokaryotic physiological state, and
      viral life strategies compared to the aphotic hypolimnion which was stable within
      sampled months. The prokaryotic host physiology as inferred from the nucleic acid
      content of prokaryotic cells (high or low nucleic acid) was strongly regulated by
      the chlorophyll concentration. The predominance of the high nucleic acid (HNA)
      prokaryotes (cells) over low nucleic acid (LNA) prokaryotes (cells) in the spring
      (HNA/LNA = 1.2) and vice versa in the summer period (HNA/LNA = 0.4) suggest that
      the natural prokaryotic communities underwent major shifts in their physiological
      states during investigated time period. The increase in the percentage of
      inducible lysogenic prokaryotes in the summer period was associated with the
      switch in the dominance of LNA over HNA cells, which coincided with the periods
      of strong resource (nutrient) limitation. This supports the idea that lysogeny
      represents a maintenance strategy for viruses in unproductive or harsh
      nutrient/host conditions. A negative correlation of percentage of lysogenic
      prokaryotes with HNA cell abundance and chlorophyll suggest that lysogenic cycle
      is closely related to prokaryotic cells which are stressed or starved due to
      unavailability of resources for its growth and activity. Our results provide
      support to previous findings that changes in prokaryote physiology are critical
      for the promotion and establishment of lysogeny in aquatic ecosystems, which are
      prone to constant environmental fluctuations.

PMID- 24910015
TI  - Diversity and distribution of freshwater testate amoebae (protozoa) along
      latitudinal and trophic gradients in China.
AB  - Freshwater microbial diversity is subject to multiple stressors in the
      Anthropocene epoch. However, the effects of climate changes and human activities
      on freshwater protozoa remain poorly understood. In this study, the diversity and
      distribution of testate amoebae from the surface sediments were investigated in
      51 Chinese lakes and reservoirs along two gradients, latitude and trophic status.
      A total of 169 taxa belonging to 24 genera were identified, and the most diverse
      and dominant genera were Difflugia (78 taxa), Centropyxis (26 taxa) and Arcella
      (12 taxa). Our analysis revealed that biomass of testate amoebae decreased
      significantly along the latitudinal gradient, while Shannon-Wiener indices and
      species richness presented an opposite trend (P < 0.05). The relationship of
      diversity and latitude is, we suspect, an artifact of the altitudinal
      distribution of our sites. Furthermore, biomass-based Shannon-Wiener index and
      species richness of testate amoebae were significantly unimodally related to
      trophic status (P < 0.05). This is the first large-scale study showing the
      effects of latitude and trophic status on diversity and distribution of testate
      amoebae in China. Therefore, our results provide valuable baseline data on
      testate amoebae and contribute to lake management and our understanding of the
      large-scale global patterns in microorganism diversity. 

PMID- 24910016
TI  - A study on the association between infectious burden and Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: Previous studies suggested that the overall burden of
      prior infections contributes to cardiovascular diseases and stroke. In the
      present study, the association between infectious burden (IB) and Alzheimer's
      disease (AD) was examined. METHODS: Antibody titers to common infectious
      pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1),
      Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were
      measured by enzyme-linked immunosorbent assay in 128 AD patients and 135 healthy
      controls. IB was defined as a composite serological measure of exposure to these
      common pathogens. RESULTS: Seropositivities toward zero-two, three and four-five
      of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%,
      44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden
      were independently associated with AD after adjusting for age, gender, education,
      APOE genotype and various comorbidities. Mini-Mental State Examination scores
      were negatively correlated with IB in all cases. Serum beta-amyloid protein
      (Abeta) levels (i.e. Abeta40, Abeta42 and total Abeta) and inflammatory cytokines
      (i.e. interferon-gamma, tumor necrosis factor alpha, interleukin-1beta and
      interleukin-6) in individuals exposed to four-five infectious pathogens were
      significantly higher than those exposed to zero-two or three pathogens.
      CONCLUSIONS: IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H.
      pylori is associated with AD. This study supports the role of
      infection/inflammation in the etiopathogenesis of AD.

PMID- 24910017
TI  - Electrochemical detection of intracellular and cell membrane redox systems in
      Saccharomyces cerevisiae.
AB  - Redox mediators can interact with eukaryote cells at a number of different cell
      locations. While cell membrane redox centres are easily accessible, the redox
      centres of catabolism are situated within the cytoplasm and mitochondria and can
      be difficult to access. We have systematically investigated the interaction of
      thirteen commonly used lipophilic and hydrophilic mediators with the yeast
      Saccharomyces cerevisiae. A double mediator system is used in which ferricyanide
      is the final electron acceptor (the reporter mediator). After incubation of cells
      with mediators, steady state voltammetry of the ferri/ferrocyanide redox couple
      allows quantitation of the amount of mediator reduced by the cells. The plateau
      current at 425 mV vs Ag/AgCl gives the analytical signal. The results show that
      five of the mediators interact with at least three different trans Plasma
      Membrane Electron Transport systems (tPMETs), and that four mediators cross the
      plasma membrane to interact with cytoplasmic and mitochondrial redox molecules.
      Four of the mediators inhibit electron transfer from S. cerevisiae. Catabolic
      inhibitors were used to locate the cellular source of electrons for three of the
      mediators.

PMID- 24910018
TI  - Non-genetic sources of variation of milk production and reproduction and
      interactions between both classes of traits in Sicilo-Sarde dairy sheep.
AB  - This work aimed to study the sources of variation in productive and reproductive
      traits of the dairy Sicilo-Sarde ewes and to further investigate the interaction
      between both classes of traits. After edits, a database containing 5935 lactation
      records collected during 6 successive years in eight dairy flocks in the North of
      Tunisia was used. Total milked milk (TMM) in the milking-only period was retained
      as productive trait. The interval from the start of the mating period to the
      subsequent lambing (IML) and the lambing status (LS) were designed as
      reproductive traits. Sicilo-Sarde ewes had an average TMM of 60.93 l (+/-44.12)
      during 132.8 days (+/-46.6) after a suckling period of 100.4 days (+/-24.9).
      Average IML was 165.7 days. In a first step, the major factors influencing milk
      production and reproductive traits were determined. The significant sources of
      variation identified for TMM were: flock, month of lambing, year of lambing,
      parity, suckling length, litter size and milking-only length. Flock*month of the
      start of the mating period, parity, year of mating and litter size were
      identified as significant factors of variation for IML, while flock*month of the
      start of the mating period, parity and year of mating were identified as
      significant sources of variation for LS. In a second step, variance components
      were estimated using a three traits threshold mixed model, which combined LS as
      categorical trait and TMM and IML as continuous traits. Repeatability estimates
      were 0.21 (+/-0.03) for TMM, 0.09 (+/-0.02) for IML, and 0.10 (+/-0.05) for LS.
      Moreover, TMM and IML were found to be favorably associated for the flock* year
      of lambing effect (-0.45+/-0.18) but unfavorably associated for the animal effect
      (0.20+/-0.09). 

PMID- 24910019
TI  - Terbium(III)-cholate functionalized vesicles as luminescent indicators for the
      enzymatic conversion of dihydroxynaphthalene diesters.
AB  - The phosphorescence intensity of unilamellar DOPC vesicles with embedded Tb(3+)
      cholate complexes depends on the concentration of dihydroxynaphthalene (DHN) as
      sensitizer in solution. This was used to monitor the enzymatic conversion of DHN
      esters or DHN glucosides by enzymes in aqueous buffered solution. 

PMID- 24910020
TI  - CpaA a novel protease from Acinetobacter baumannii clinical isolates deregulates
      blood coagulation.
AB  - Acinetobacter baumannii is an important nosocomial pathogen that displays high
      antibiotic resistance. It causes a variety of infections including pneumonias and
      sepsis which may result in disseminated intravascular coagulation. In this work,
      we identify and characterize a novel secreted, zinc-dependent, metallo
      endopeptidase CpaA (coagulation targeting metallo-endopeptidase of Acinetobacter
      baumannii) which deregulates human blood coagulation in vitro and thus is likely
      to contribute to A. baumannii virulence. Three quarters of the clinical isolates
      tested (n = 16) had the cpaA gene; however, it was absent from two type strains,
      A. baumannii ATCC 17978 and A. baumannii ATCC 19606. The CpaA protein was
      purified from one clinical isolate and was able to cleave purified factor (F) V
      and fibrinogen and reduce the coagulation activity of FV in human plasma. CpaA
      treated plasma showed reduced clotting activity in contact pathway-activated
      partial thromboplastin time (aPTT) assays, but increased clotting activity in
      tissue factor pathway prothrombin time (PT) assays. A significant portion of
      clinically relevant A. baumannii isolates secrete a protease which targets and
      deregulates the coagulation system.

PMID- 24910021
TI  - Beyond symptom control for attention-deficit hyperactivity disorder (ADHD): what
      can parents do to improve outcomes?
AB  - Attention-deficit hyperactivity disorder (ADHD) and its associated behavioural
      manifestations develop and progress as the result of complex gene-environment
      interactions. Parents exert a substantial influence and play a major role in
      their child's social environment. Despite this, recent evidence has suggested
      that adapting the child's environment via parenting interventions has minimal
      effects on child ADHD symptoms when analysing data from informants who are
      probably blind to treatment allocation. However, adverse parenting and family
      environments may act as a source of environmental risk for a number of child
      outcomes beyond ADHD symptoms. This is a narrative review that critically
      discusses whether parenting interventions are beneficial for alternative
      functioning outcomes in ADHD including neuropsychological, academic and social
      functioning and disruptive behaviour and how parenting and familial environments
      may be associated with these outcomes. In addition, the review explores how
      parental depression and parenting efficacy impact on capacity for optimal
      parenting and whether parenting interventions benefit parents too. A review of
      the evidence suggests that with modification, parenting interventions are
      beneficial for a number of outcomes other than ADHD symptom reduction. Improving
      the parent-child relationship may have indirect benefits for disruptive
      behaviour. Furthermore, parenting behaviours may directly benefit child
      neuropsychological, academic and social functioning. Parenting interventions can
      have therapeutic benefits for parents as well as children, which is important as
      parent and child well-being is likely to have a transactional relationship.
      Evaluation of the clinical success of parenting interventions should focus on a
      wider range of outcomes in order to aid understanding of the multifaceted
      benefits that they may be able to offer. Parenting interventions should not be
      seen as a redundant adjunct to medication in multi-modal treatment approaches for
      ADHD; they have the potential to target outcomes that, at present, medication
      seems less able to improve. 

PMID- 24910022
TI  - Use of imatinib in a patient with cutaneous vasculopathy in the context of von
      Recklinghausen disease/neurofibromatosis.
AB  - von Recklinghausen disease/neurofibromatosis (NF) is caused by an autosomal
      dominant mutation in NF1, resulting in a deficiency of neurofibromin 1, a protein
      with a tumour suppressor function in the Ras-extracellular regulated kinase
      pathway. The disease comprises a variety of clinical manifestations, including
      vascular abnormalities. Large vessel abnormalities are well known, while small
      vessels of the skin are very rarely involved. The latter can cause livedo,
      necrosis and painful ulcers. For such ulcers, all invasive therapies (e.g.
      surgery and radiotherapy) are harmful and should be avoided. Herein, we describe
      a patient with NF and cutaneous vasculopathy treated with imatinib, a tyrosine
      kinase inhibitor. 

PMID- 24910023
TI  - Clinical association between non-alcoholic fatty liver disease and the
      development of hypertension.
AB  - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is getting an
      increasing attention for its clinical implications on cardiovascular disease
      (CVD). However, epidemiologic data are not so evident to sustain the causative
      association between NAFLD and hypertension, the major cause of CVD. Accordingly,
      we designed this study to investigate the clinical association between NAFLD and
      the development of hypertension. METHODS: To assess the natural course of blood
      pressure according to degree of NAFLD (normal, mild, and moderate to severe), we
      conducted a prospective cohort study on the 22 090 Korean men without
      hypertension for 5 years. We serially checked the various metabolic factors
      including systolic and diastolic blood pressure in order to monitor the
      development of hypertension. RESULTS: The incidence rate of hypertension
      increased according to the degree of NAFLD (normal: 14.4%, mild: 21.8%, moderate
      to severe: 30.1%, P < 0.001). Even after adjusting for other multiple covariates,
      the hazard ratios (95% confidence intervals) for hypertension were higher in the
      mild group (1.07; 1.00-1.15) and moderate to severe group (1.14; 1.00-1.30),
      compared with normal group, respectively (P for trend < 0.001). CONCLUSION:
      Development of hypertension is more potentially associated with the more
      progressive NAFLD than normal or milder state. In addition, NAFLD was an
      independent risk factor for hypertension.

PMID- 24910024
TI  - Vitamin D: present and future.
AB  - In recent years has been a growing interest by vitamin D, not only for its
      important role in the bone mineral metabolism, but also by the extra-osseous
      effects. Most of the scientific societies consider that deposits are sufficient
      if the serum concentration of 25-OH vitamin D is above 30ng/ml and are considered
      deficient if levels are below 20ng/ml. The majority of studies found that
      supplements of calcium plus vitamin D have a positive effect in reducing the risk
      of fracture and the risk of falls in the elderly, although several specifies that
      doses should be 700-1.000 IU daily. The treatment of the deficit can be performed
      with vitamin D2, D3 as well as calcidiol or the active metabolite calcitriol. In
      certain pathologies also selective vitamin D receptor activators can be used. 

PMID- 24910025
TI  - Appendix in porcelain.

PMID- 24910026
TI  - Distinct cytokine pattern in response to different bacterial pathogens in human
      brain abscess.
AB  - Brain abscess is a focal suppurative process. Host inflammatory response in Gram
      type and specific bacteria has not been studied in brain abscess. A total of 57
      brain abscess patients with monomicrobial infections were studied for Th1 (TNF
      alpha, IFN-gamma, IL1-beta), Th2 (IL-4, IL-10) and Th17 (IL-17, IL-23) cytokine
      response by reverse-transcriptase PCR and ELISA. Th1 and Th17 cytokines were
      significantly elevated in Gram positive (Staphylococcus aureus and Streptococcus
      intermedius) and Th2 cytokine (IL-10) in Gram negative (Bacteroides fragilis and
      Escherichia coli) infections (p<0.05). Cytokine levels were significantly higher
      in abscess than blood (p<0.001). Elevated levels of several inflammatory
      cytokines (TNF-alpha, IFN-gamma, IL1-beta, IL-17 and IL-23) were associated with
      the duration of symptoms; predisposing factors also influenced the levels of
      several cytokines. The expression of inflammatory cytokines in abscess was
      influenced by the bacterial pathogen, duration of symptoms and predisposing
      factors. Local milieu of brain plays significant role in secretion of various
      cytokines.

PMID- 24910027
TI  - Enhanced formaldehyde oxidation on Pt/MnO2 catalysts modified with alkali metal
      salts.
AB  - Novel Pt/MnO2 catalysts modified with alkali metal salts were prepared and
      exhibited excellent catalytic activity for formaldehyde oxidation. The effects of
      both cation and anion in the salts were investigated on the structure of
      catalysts and their catalytic activity. The Na(+) modification was demonstrated
      to be a facile and effective method to improve the catalysts performance for
      formaldehyde oxidation, but the anions remaining on the support might act as a
      mild poison by covering the surface active sites of manganese oxides. The
      enhancing effect of anions in the salts follows the order of CO3(2-)>SO4(2-)>NO3(
      ). A 100% formaldehyde conversion can be obtained at 50 degrees C over the Na2CO3
      modified catalyst. Further analyses indicate that strong metal-support
      interaction, well-dispersed Pt nanoparticles with small particle sizes and large
      surface area are important for high catalytic activity. 

PMID- 24910028
TI  - Effect of annealing on the structural, morphological and photoluminescence
      properties of ZnO thin films prepared by spin coating.
AB  - Zinc oxide (ZnO) thin films were deposited on silicon substrates by a sol-gel
      method using the spin coating technique. The ZnO films were annealed at 700
      degrees C in an oxygen environment using different annealing times ranging from 1
      to 4 h. It was observed that all the annealed films exhibited a hexagonal
      wurtzite structure. The particle size increased from 65 to 160 nm with the
      increase in annealing time, while the roughness of the films increased from 2.3
      to 10.6 nm with the increase in the annealing time. Si diffusion from the
      substrate into the ZnO layer occurred during the annealing process. It is likely
      that the Si and O2 influenced the emission of the ZnO by reducing the amount of
      Zn defects and the creation of new oxygen related defects during annealing in the
      O2 atmosphere. The emission intensity was found to be dependent on the
      reflectance of the thin films.

PMID- 24910029
TI  - Hydraulic pressures generated in magnetic ionic liquids by paramagnetic fluid/air
      interfaces inside of uniform tangential magnetic fields.
AB  - HYPOTHESIS: Magnetic Ionic Liquid (MILs), novel magnetic molecules that form
      "pure magnetic liquids," will follow the Ferrohydrodynamic Bernoulli
      Relationship. Based on recent literature, the modeling of this fluid system is an
      open issue and potentially controversial. EXPERIMENTS: We imposed uniform
      magnetic fields parallel to MIL/air interfaces where the capillary forces were
      negligible, the Quincke Problem. The size and location of the bulk fluid as well
      as the size and location of the fluid/air interface inside of the magnetic field
      were varied. MIL properties varied included the density, magnetic susceptibility,
      chemical structure, and magnetic element. FINDINGS: Uniform tangential magnetic
      fields pulled the MILs up counter to gravity. The forces per area were not a
      function of the volume, the surface area inside of the magnetic field, or the
      volume displacement. However, the presence of fluid/air interfaces was necessary
      for the phenomena. The Ferrohydrodynamic Bernoulli Relationship predicted the
      phenomena with the forces being directly related to the fluid's volumetric
      magnetic susceptibility and the square of the magnetic field strength.
      [emim][FeCl4] generated the greatest hydraulic head (64-mm or 910 Pa at 1.627
      Tesla). This work could aid in experimental design, when free surfaces are
      involved, and in the development of MIL applications.

PMID- 24910030
TI  - Effects of Ag doping on the photocatalytic disinfection of E. coli in bioaerosol
      by Ag-TiO2/GF under visible light.
AB  - Ag doped TiO2/glass fibers (Ag-TiO2/GF) were prepared and used for photocatalytic
      disinfection of Escherichia coli (E. coli) in an indoor air environment. The
      prepared photocatalysts were characterized using scanning electron microscope
      (SEM) for morphology, X-ray diffraction (XRD) for microstructure, UV-Visible
      diffuse reflectance spectra (DRS) for optical properties and X-ray photoelectron
      spectroscopy (XPS) to determine elemental state. The optimized weight fraction of
      TiO2 in the TiO2/glass fiber (TiO2/GF) was 3%. The silver content in Ag/TiO2 was
      altered from 1% to 10% to investigate the optimal ratio of Ag doped on the
      TiO2/GF for the photocatalytic disinfection of E. coli. Doped Ag enhanced the
      electron-hole separation as well as charge transfer efficiency between the
      valance band and the conduction band of TiO2. The generated electron-hole pairs
      reacted with water and molecular oxygen to form strong oxidative radicals, which
      participated in the oxidation of organic components of E. coli, resulting in
      bacterial death. The photocatalytic disinfection activity under visible light
      increased with the increase in silver content up to 7.5% and then decreased
      slightly with further increasing Ag content. Among the three humidity conditions
      used in this study (40+/-5%, 60+/-5%, 80+/-5%), the highest disinfection ratio of
      E. coli by the photocatalytic system was observed in the intermediate humidity
      level followed by the high humidity level. Using the 7.5% Ag-TiO2/GF and the
      intermediate level of humidity (60+/-5%), the highest disinfection ratio and
      disinfection capacity of E. coli were 93.53% and 26 (CFU/s cm(2)), respectively.

PMID- 24910032
TI  - Tailoring micro-mesoporosity in activated carbon fibers to enhance SO2 catalytic
      oxidation.
AB  - Enhanced SO2 adsorption of activated carbon fibers is obtained by tailoring a
      specific micro-mesoporous structure in the fibers. This architecture is obtained
      via metal catalytic activation of the fibers with a novel precursor, cobalt
      naphthenate, which contrary to other precursors, also enhances spinnability and
      carbon fiber yield. In the SO2 oxidation, it is demonstrated that the combination
      of micropores and large mesopores is the main factor for an enhanced catalytic
      activity which is superior to that observed in other similar microporous
      activated carbon fibers. This provides an alternative way for the development of
      a new generation of catalytic material. 

PMID- 24910031
TI  - One-step/one-pot decoration of oxide microparticles with silver nanoparticles.
AB  - HYPOTHESIS: Heterogeneous nucleation of silver oxide (Ag2O) onto oxide
      microparticles (OMPs) followed by spontaneous thermal decomposition produce
      nanostructures made of OMPs decorated with silver nanoparticles (OMP|AgNPs).
      EXPERIMENTS: Colloidal chemistry methods have been used to produce the decoration
      of OMPs with silver nanoparticles (AgNPs), by carrying out the Ag2O
      precipitation/thermal decomposition. The process is driven in water enriched
      acetone medium containing NaOH, NH3, AgNO3 and SiO2MPs as substrate. Optical and
      morphological properties of OMP|AgNPs were characterized by using STEM, EDS,
      HRTEM and Raman spectroscopy. FINDINGS: A new synthetic method to decorate OMPs
      (TiO2, SiO2) with metallic AgNPs in a single step/single pot reaction is proven
      effective to produce OMP|AgNPs either in aqueous or water enriched media.

PMID- 24910033
TI  - Superamphiphobic nanofibrous membranes for effective filtration of fine
      particles.
AB  - The worldwide demands are rising for an energy-efficient and cost-effective
      approach that can provide advanced nanofibrous membranes with high filtration
      performance and superior antifouling properties. Here we report a novel
      synthesized fluorinated polyurethane (FPU) modified nanofibrous membrane
      optimized to achieve oil and non-oil aerosol particle filtration. By employing
      the FPU incorporation, the polyacrylonitrile/polyurethane (PAN/PU) composite
      membranes were endowed with superhydrophobicity with a water contact angle of 154
      degrees  and superoleophobicity with an oil contact angle of 151 degrees .
      Morphology, surface wettability, porous structure, and filtration performance
      could be manipulated by tuning the solution composition as well as the
      hierarchical structure. Furthermore, the as-prepared membranes can capture, for
      the first time, a range of different oil aerosol particles in a single-unit
      operation, with >99.9% filtration efficiency, by using the combined contribution
      of fiber diameter and surface roughness acting on the objective particles.
      Exemplified here by the construction of superamphiphobic nanofibrous membrane,
      numerous applications of this medium includes high efficiency particulate air
      filters, ultra-low penetration air filters, and respiratory protection equipment.

PMID- 24910034
TI  - PEGylated long circulating nanostructured lipid carriers for Amoitone B:
      preparation, cytotoxicity and intracellular uptake.
AB  - Amoitone B is a newly synthesized derivative of antitumor drug cytosporone B,
      which exhibits excellent anticancer activity in vivo. Nevertheless, the water
      insolubility and short biological half-life limit its further development. In the
      present study, polyethylene glycol-modified, Amoitone B-loaded long circulating
      nanostructured lipid carriers (AmB-PEG-NLC) were prepared by the emulsion
      evaporation and low temperature-solidification method. The in vitro antitumor
      activity and intracellular uptake of AmB-PEG-NLC in the human colon cancer SW620
      cells and liver cancer HepG2 cells were evaluated in detail. MTT assay was
      employed to investigate the inhibition effect on cellular viability. Propidium
      iodide and DAPI staining were performed to visually examine the fluorescent
      morphology changes of the cells incubated with AmB-PEG-NLC. Flow cytometry was
      utilized to determine the influence of AmB-PEG-NLC on apoptosis of SW620. The
      intracellular uptake was observed by rhodamine B, a fluorescent maker.
      Cytotoxicity assay, observation of morphological changes and apoptosis
      examination revealed that AmB-PEG-NLC could markedly enhance the cytotoxicity of
      AmB against cancer cell compared to AmB solution and AmB-NLC. An increased uptake
      of PEG-NLC was obtained compared with NLC in SW620 cells, which might attribute
      to the effect of PEG. Based on these results, AmB-PEG-NLC could be a promising
      delivery system for AmB with effective cancer therapy. 

PMID- 24910035
TI  - Self-assembly study and formation of hydrophobized PVA dense and stable
      nanoparticles loaded with cholesterol or a steroid-type drug.
AB  - This work reports the preparation of modified poly(vinyl alcohol) PVA decorated
      with two different hydrophobic side-arms. Each material displays various
      percentages of pendant oleate and cholesteryl groups. The molar amount and the
      difference between their respective physico-chemical contributions are able to
      induce size variations of the formed micelles in aqueous media. These large
      amphiphilic structures hold a hydrophobic core ready for the incorporation of
      strong hydrophobic species such as cholesterol or prednisolone, a well-known low
      water soluble steroid-type drug. In the presence of a steroid derivative, the
      modified PVA could form smaller and dense nanoparticles loaded in their cores.
      The synthesis of each polymer was controlled by (1)H NMR and FT-IR
      spectroscopies. The size of the empty micelles and the diameter of the loaded
      nanoparticles were determined by dynamic light scatting (DLS) studies. The
      measurement of the critical micelle concentration (CMC) was carried out for each
      polymer sample by fluorescence probing using pyrene. The amount of cholesterol
      incorporated into the hydrophobic core was estimated and all binding modes
      between the steroids and each amphiphilic polymer were also discussed in regard
      to their size distribution, concentration and stability. 

PMID- 24910037
TI  - Facile synthesis of ammonium vanadium oxide nanorods for Na-ion battery cathodes.
AB  - A simple and versatile method for preparation of NH4V4O10 nanorods is developed
      via a simple hydrothermal route. NH4V4O10 nanorods display better cycling
      stability than NH4V4O10 microflowers as a cathode material for sodium-ion
      batteries because of the changes in crystalline structure, which would be in
      favor of superior discharge capacity. Furthermore, the enhancement of
      electrochemical performance for NH4V4O10 nanorods at high current rates is
      offered in addition of fluoroethylene carbonate to electrolyte. Such a good
      performance results from the improvement of reaction kinetics and Na-ion transfer
      rate. 

PMID- 24910036
TI  - Adsorption of zwitterionic fluoroquinolone antibacterials to goethite: a charge
      distribution-multisite complexation model.
AB  - Fluoroquinolone (FQ) antibacterials are aquatic contaminants of emerging concern
      (CEC), and adsorption to mineral surfaces is expected to play an important role
      in the fate, transport, and treatment of FQs. This study characterizes and models
      the adsorption of a zwitterionic FQ, ofloxacin (OFX), to goethite (alpha-FeOOH)
      over a wide range of pH (3-11), OFX concentration (20-500 MUM), and electrolyte
      compositions (0.001-0.1M NaCl and NaClO4). Comparing OFX adsorption to structural
      analogues demonstrates that the carboxylate group is essential for binding to
      goethite. ATR-FTIR measurements indicate that FQs complex to goethite surfaces
      through carboxylate and carbonyl oxygen atoms, and that ClO4(-) co-adsorbs with
      OFX. Adsorption of the zwitterionic OFX increases with increasing ionic strength
      and is enhanced in NaClO4 relative to NaCl electrolyte, whereas adsorption of a
      non-zwitterionic analogue is insensitive to ionic strength. A CD-MUSIC (charge
      distribution-multisite complexation) model, incorporating multiple modes of
      surface complexation constrained by spectroscopic measurements and the
      crystallographic distribution of goethite surface sites, yields accurate
      predictions over wide-ranging solution conditions. According to the model, OFX
      adsorbs predominantly by inner-sphere complexation on terminal surfaces of the
      rod-shaped goethite crystals in NaCl electrolyte, and OFX-ClO4(-) ion pairing in
      NaClO4 induces formation of additional inner- and outer-sphere surface complexes
      on multiple crystal faces of goethite.

PMID- 24910038
TI  - Characterization of glucose oxidation by gold nanoparticles using nanoceria.
AB  - Gold nanoparticles (AuNPs) can oxidize glucose, producing hydrogen peroxide and
      gluconic acid, which are the same products as those generated by glucose oxidase
      (GOx). In this regard, AuNPs are a nanozyme. Herein, a new colorimetric method is
      developed to understand the surface chemistry of gold nanoparticles for this
      oxidation reaction. The color of nanoceria is changed to yellow by the hydrogen
      peroxide generated during glucose oxidation. Using this assay, we find that
      adsorption of small molecules such as citrate does not deactivate AuNPs, while
      adsorption of polymers including serum proteins and high molecular weight
      polyethylene glycol inhibits glucose oxidation. In addition to glucose, AuNPs can
      also oxidize galactose. Therefore, this reaction is unlikely to be directly
      useful for glucose detection for biomedical applications. On the other hand,
      AuNPs might serve as a general oxidase for a broad range of substrates. The
      glucose oxidation reaction is slower at lower pH. Since the reaction generates an
      acid product, glucose oxidation becomes slower as the reaction proceeds. The
      effects of temperature, AuNP size, and reaction kinetics have been systematically
      studied. This work provides new insights regarding the surface chemistry of AuNPs
      as a nanozyme. 

PMID- 24910039
TI  - Spontaneous grafting: a novel approach to graft diazonium cations on gold
      nanoparticles in aqueous medium and their self-assembly on electrodes.
AB  - The spontaneous grafting of aminophenyl groups on gold nanoparticles (AuNPs) by
      reaction with in situ generated 4-aminophenyl diazonium cations (APD) in an
      aqueous medium was described. The spontaneous grafting was likely to proceed by
      transfer of electrons from AuNPs to the APD cations to form an aminophenyl
      radical and subsequent attachment with AuNPs. The aminophenyl (AP) functionalized
      gold nanoparticles (AP-AuNPs) were characterized by UV-visible spectroscopy, high
      resolution-transmission electron microscopy (HR-TEM), X-ray diffraction, FT-IR
      spectroscopy, X-ray photoelectron spectroscopy (XPS) and surface-enhanced Raman
      spectroscopy (SERS). The absence of characteristic vibrational bands
      corresponding to diazonium group in the FT-IR spectrum confirmed the reduction of
      the aminophenyl diazonium cations at the surface of AuNPs. The spontaneous
      attachment of AP on AuNPs was confirmed by XPS from the observed binding energy
      values for -NH2 at 399.4 eV and -N=N- at 400.2 eV. The SERS spectrum reveals the
      presence Au-C (437 cm(-1)) bond on AP-AuNPs. Further, the AP-AuNPs were self
      assembled on GC/ITO electrode (AP-AuNPs modified electrode) with the aid of free
      amine groups present on the surface of AP-AuNPs via Michael's nucleophilic
      addition reaction. The AP-AuNPs modified electrode was characterized by cyclic
      voltammetry, impedance spectroscopy, UV-visible spectroscopy and scanning
      electron microscopy. Impedance studies show that the electron transfer reaction
      of [Fe(CN)6](3-/4-) was higher at the AP-AuNPs modified electrode (1.81*10(-4) cm
      s(-1)) than at bare (3.77*10(-5) cm s(-1)) GC electrode. Finally, the
      electrocatalytic activity of the AP-AuNPs modified electrode was demonstrated by
      studying the oxidation of dopamine (DA).

PMID- 24910040
TI  - BiFeO3/alpha-Fe2O3 core/shell composite particles for fast and selective removal
      of methyl orange dye in water.
AB  - BiFeO3/alpha-Fe2O3 core/shell composite particles featuring fast removal,
      selective adsorption, and magnetic recycle capability on anionic methyl orange
      (MO) dye in water was synthesized by a two-step chemical route. A discontinuous
      and rough shell consisting of the alpha-Fe2O3 nanoparticles was deposited on the
      BiFeO3 core surface preferentially, forming raspberry-like core/shell particle
      morphology. The core/shell particles demonstrated a pronounced adsorption to the
      MO molecules when compared with particulate mixtures of the same molar ratio. At
      an initial MO concentration of 2.5*10(-5) M, nearly 80% of the dye molecules were
      captured by the core/shell particles within 5 min at an acidic pH of 5.2.
      Desorption of the MO dye could be made easily when the solution pH was adjusted
      to 9.5. This together with a minute adsorption capacity (<2%) from solutions
      consisting of cationic methylene blue (MB) dye suggests that the adsorption
      selectivity was in part due to electrostatic interactions between the dye
      molecules and the core/shell particles.

PMID- 24910041
TI  - Interfacial molecular imprinting of Stober particle surfaces: a simple approach
      to targeted saccharide adsorption.
AB  - The use of surfactant headgroups for interfacial imprinting is established as a
      simple and tunable approach to create molecularly imprinted silica nanoparticles
      based on a modification of the Stober method. Adsorption of D-glucose and D
      xylose (initial concentrations ranging from 0.139 to 1.67 mol/l) is measured on
      silica nanoparticles created by the addition of a glucose-based surfactant (n
      octyl-beta-D-glucopyranoside (C8G1)) or surfactant mixtures (C8G1 and
      cetyltrimethylammonium bromide (CTAB)) to Stober particles shortly after their
      precipitation. Silica particles synthesized in the presence of C8G1 as an
      imprinting surfactant have a significantly higher affinity for glucose over
      xylose (as much as 3.25 times greater at 0.25 M saccharide), and an enhanced
      affinity for glucose relative to non-imprinted silica particles (as much as 4
      times greater at 0.25 M), which adsorb glucose and xylose similarly. Glucose
      imprinting is significantly enhanced using a surfactant mixture of 1:1 C8G1/CTAB.
      The interfacial activity of the nonionic imprinting surfactant at the silica
      surface is suggested to be improved by the presence of interfacial cationic CTAB,
      which is driven to the silica surface through electrostatic interactions. The
      concept of imprinting through the interaction of surfactant headgroups with the
      soft surface of silica particles is supported by the importance of the time of
      addition of the surfactants. The greatest enhancement in glucose adsorption is
      observed when the surfactants are added 1 min after precursor addition (at the
      onset of aggregated particle formation, as indicated by solution turbidity) and
      the silica affinity for glucose decreases with the time of surfactant addition.
      The versatility of the surfactant imprinting of Stober particles is demonstrated
      by the enhanced adsorption of xylose relative to glucose on particles imprinted
      using a 1:1 mixture of n-octyl-beta-D-xylopyranoside and CTAB, suggesting that
      the process can be customized to selectively adsorb target molecules of interest.

PMID- 24910042
TI  - Impact of interfacial cholesterol-anchored polyethylene glycol on sterol-rich non
      phospholipid liposomes.
AB  - HYPOTHESIS: Liposomes made of single-chain amphiphiles and a large amount of
      sterols display several advantages including a limited permeability. In the
      present paper, we examine the possibility to prepare such non-phospholipid
      liposomes with interfacial polyethylene glycol (PEG) in order to improve their
      circulation in the blood stream. Cholesterol (Chol) was chosen as the PEG anchor.
      EXPERIMENTS: The phase behavior of mixtures of palmitic acid (PA) and cholesterol
      including various proportions of PEGylated cholesterol (PEG-Chol) was
      characterized. In conditions leading to the formation of fluid bilayers,
      properties of the resulting liposomes were assessed. FINDINGS: Up to 20 mol% of
      PEGylated cholesterol could be introduced without significant perturbations in
      fluid bilayers made of PA and cholesterol. With 10 mol% PEG-Chol, PA/Chol/PEG
      Chol liposomes showed a very limited permeability to calcein and doxorubicin.
      Doxorubicin could be actively loaded in PA/Chol/PEG-Chol liposomes with a high
      drug loading efficiency and a high drug to lipid ratio. Pharmaco-kinetic
      experiments in rats indicated that interfacial PEG reduced the clearance of
      PA/Chol liposomes compared to the naked ones. However the lifetime of these non
      phospholipid liposomes in the blood circulation was considerably shorter than
      that observed for control PEGylated phospholipid liposomes, a phenomenon
      associated with the negative interfacial charge of the PA/Chol/PEG-Chol
      liposomes.

PMID- 24910044
TI  - Improved performance of dye-sensitized solar cells using gallium nitride-titanium
      dioxide composite photoelectrodes.
AB  - Dye-sensitized solar cells (DSSCs) are fabricated with gallium nitride-titanium
      dioxide (GaN-TiO2) composite photoelectrodes to enhance the power conversion
      efficiency. The value of power conversion efficiency increases with the
      incorporation of GaN in TiO2 matrix and reaches a maximum at 0.05 wt% GaN.
      Internal resistance in the DSSC is characterized by electrochemical impedance
      spectroscopy (EIS). From the EIS of electrolyte/dye/GaN-TiO2 interface
      resistances under illumination and in the dark, a decrease in the charge transfer
      resistance and an increase in the charge recombination resistance of the DSSCs
      are obtained after the inclusion of GaN (0.01-0.05 wt%) in the TiO2 matrix. The
      power conversion efficiency of the DSSC based on the GaN (0.05 wt%)-TiO2
      composite photoelectrode is enhanced by ~61% in comparison with a pristine TiO2
      photoelectrode.

PMID- 24910045
TI  - Electrochemical properties of boron-doped ordered mesoporous carbon as
      electrocatalyst and Pt catalyst support.
AB  - The electrochemical properties of boron-doped ordered mesoporous carbon (BOMC) as
      an electrode material and Pt catalyst support were investigated. The BOMC was
      synthesized and its structure was examined by transmission electron microscopy
      (TEM), scanning electron microscopy, nitrogen adsorption-desorption, X-ray
      diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). More
      defective sites were introduced into OMC by the doping of boron. Six
      electroactive compounds were employed to investigate their electrochemical
      responses on BOMC and OMC modified glassy carbon electrodes. The BOMC, with more
      defective sites, exhibited high activity toward the electroactive compounds. The
      property of BOMC of supporting platinum nanoparticle catalyst was examined. Pt
      nanoparticles were loaded onto BOMC and OMC, and this was confirmed by TEM, XPS
      and thermogravimetric analysis. Pt nanoparticles with an average diameter of 2.62
      nm were deposited on BOMC. The doping of boron into OMC facilitates the
      dispersion of Pt nanoparticles. Pt nanoparticles supported on BOMC (Pt-BOMC) and
      Pt nanoparticles supported on OMC (Pt-OMC) were electrochemically characterized.
      The electrocatalytic activity of Pt-BOMC toward methanol oxidation reaction was
      compared with that of Pt-OMC and commercial Pt-C catalyst. The results show that
      the electrocatalytic activity of BOMC is significantly higher than that of other
      used catalysts.

PMID- 24910043
TI  - Sn-Mn binary metal oxides as non-carbon sorbent for mercury removal in a wide
      temperature window.
AB  - A series of Sn-Mn binary metal oxides were prepared through co-precipitation
      method. The sorbents were characterized by powder X-ray diffraction (powder XRD),
      transmission electronic microscopy (TEM), H2-temperature-programmed reduction (H2
      TPR) and NH3-temperature-programmed desorption (NH3-TPD) methods. The capability
      of the prepared sorbents for mercury adsorption from simulated flue gas was
      investigated by fixed-bed experiments. Results showed that mercury adsorption on
      pure SnO2 particles was negligible in the test temperature range, comparatively,
      mercury capacity on MnOx at low temperature was relative high, but the capacity
      would decrease significantly when the temperature was elevated. Interestingly,
      for Sn-Mn binary metal oxide, mercury capacity increased not only at low
      temperature but also at high temperature. Furthermore, the impact of SO2 on
      mercury adsorption capability of Sn-Mn binary metal oxides was also investigated
      and it was noted that the effect at low temperature was different comparing with
      that of high temperature. The mechanism was investigated by diffuse reflectance
      infrared Fourier transform spectroscopy (DRIFTs). Moreover, a mathematic model
      was built to calculate mercury desorption activation energy from Sn to Mn binary
      metal oxides. 

PMID- 24910046
TI  - Pure monoclinic La(1-x)Eu(x)PO4 micro-/nano-structures: fast synthesis, shape
      evolution and optical properties.
AB  - Rare-earth-doped LaPO4 crystals have been attracting considerable interest. In
      this work, we reported the fast syntheses of LaPO4 and Eu-doped LaPO4 crystals
      via a simple oil-bath route, employing La(NO3)3 and KH2PO4 as the original
      reactants, Eu2O3 as the dopant. The reaction was carried out in ethylene glycol
      system at 120 degrees C for 30 min without any assistance of surfactants or
      templates. X-ray powder diffraction analyses showed that pure monoclinic LaPO4
      form was obtained in the system without Eu(3+) ions, and the above phase was not
      changed after integrating Eu(3+) ions into LaPO4 matrix. However, electron
      microscopy observations discovered that the integration of Eu(3+) ions into LaPO4
      matrix obviously changed the morphology and size of the final La(1-x)Eu(x)PO4
      crystals. With the increase in Eu(3+) amount from 0 to 0.35, the shape of the
      final product varied from homogeneous egg-like nanospheroids, to irregular grains
      with microscales, and to homogeneous microspheroids. Also, the Eu(3+) ion content
      in La(1-x)Eu(x)PO4 markedly affected the photoluminescence properties of the
      final product. When x=0.2, the product exhibited the strongest PL emission.

PMID- 24910047
TI  - Uniform cross-linked cellulase aggregates prepared in millifluidic reactors.
AB  - HYPOTHESIS: Uniform cross-linked cellulase aggregate (XCA) can be prepared by
      using a millifluidic reactor which consists of two inlets and a Y-junction,
      because mixing pattern and spatial distribution of reactants can be controlled
      precisely. EXPERIMENTS: Aqueous cellulase solution is mixed with acetonitrile (as
      a precipitant) and 20 mM of glutaraldehyde (as a cross-linker) at the Y-junction.
      XCA is collected from the outlet of the reactor. FINDINGS: Uniform XCA, with an
      average size between 200 nm and 400 nm, can be formed inside the reactor. Unlike
      free cellulase, XCA is insoluble such that it can be filtered out from the
      solution. It can be used alone or absorb on silica gel (XCA-Si) as a catalyst for
      hydrolyzing carboxymethyl cellulose (CMC). Interestingly, XCA-Si shows highest
      activity at pH 4.8 and 50 degrees C, which is similar to the optimal condition of
      free cellulase. Moreover, XCA-Si is more stable than free cellulase at high
      temperature (>60 degrees C). It precipitates naturally and can be recycled at
      least 5 times after the hydrolysis of CMC.

PMID- 24910049
TI  - Graphene strongly wrapped TiO2 for high-reactive photocatalyst: a new sight for
      significant application of graphene.
AB  - A new idea was employed to simultaneously reduce graphene oxide (GO) and wrap it
      on the surface of high-reactive anatase TiO2 for fabricating novel TiO2-graphene
      (GP) hybrid materials. The process was based on the surface negatively charged
      property of GO. With the introduction of strong chemical interaction between TiO2
      and GP, the GP wrapped TiO2 gives a strong red-shift of the light absorption edge
      and a further narrowed bandgap compared to that of GP randomly supported TiO2.
      This structure can also significantly enhance the separation efficiency of
      photogenerated electrons and holes. Furthermore, in contrast to the normal
      anatase TiO2, as-prepared TiO2 is dominated with the high-reactive {001} facet.
      The superiority of the formed "core-shell" structure is confirmed by
      photocatalytic degradation of methylene blue (MB) under the xenon lamp and
      visible light irradiation. New photocatalytic mechanisms are also proposed based
      on the obtained results. This work may open a new doorway for new significant
      application of GP to prepare more GP-based high-reactive photocatalysts for
      environmental protection. 

PMID- 24910048
TI  - The effect of hydrophilic and hydrophobic block length on the rheology of
      amphiphilic diblock Polystyrene-b-Poly(sodium methacrylate) copolymers prepared
      by ATRP.
AB  - Following our previous investigation on the effect of molecular architecture on
      the rheology of Polystyrene-b-Poly(sodium methacrylate) copolymers (PS-b-PMAA),
      we consider here diblock PS-b-PMAA copolymers characterized by a different length
      of either the hydrophilic or the hydrophobic block. Various copolymers
      characterized by different PS or PMAA block length have been prepared by ATRP
      (kinetics is also discussed) and studied from the point of view of their
      rheological behaviour in water. To the best of our knowledge, this is the first
      systematic investigation concerning the effect of block length on the rheology of
      diblock polyelectrolytes. We found that the hydrophobic block length has small
      influence on the rheology. Surprisingly, the polymers with shortest PMAA blocks
      yield the strongest gels at high concentration. A simple model based on the
      classical theories of self-assembly and percolation of amphiphilic polymers has
      been here developed in order to explain the observed data. 

PMID- 24910050
TI  - Formation of PDADMAC monolayers evaluated in situ by QCM and streaming potential
      measurements.
AB  - Kinetics of adsorption and monolayer stability of the cationic polyelectrolyte
      poly(diallyldimethylammonium chloride) (PDADMAC) were determined. Initially, the
      bulk characteristics of the polyelectrolyte were acquired using the DLS and
      microelectrophoretic measurements. These comprised the diffusion coefficient and
      electrophoretic mobility determined as a function of ionic strength at pH 5.8.
      From these measurements, the hydrodynamic diameter, zeta potential and the
      amounts of electrokinetic charge per molecule were calculated. Subsequently, the
      kinetics of PDADMAC adsorption was evaluated under in situ conditions using the
      quartz crystal microbalance with dissipation (QCM-D) and streaming potential
      measurements. The latter allowed one to derive the calibration dependencies of
      the zeta potential on the polyelectrolyte coverage for various ionic strength
      successfully interpreted in terms of the 3-dimensional (3D) electrokinetic model.
      Using these data, the PDADMAC desorption kinetics were quantitatively analyzed.
      In this way, the desorption constants, the equilibrium adsorption constants, and
      the binding energies of PDADMAC were determined. The energy varied between -20.5
      and -19.7 kT, for ionic strength of 10(-3) and 0.15M, respectively. This agree
      with the proposed model of discrete electrostatic interactions among ion pairs
      present at the polyelectrolyte chain and the substrate surface. The mean-field
      electrostatic interactions approach proved inadequate.

PMID- 24910051
TI  - Iron-mediated oxidation of arsenic(III) by oxygen and hydrogen peroxide:
      dispersed versus resin-supported zero-valent iron.
AB  - The goal of this study is to assess the differences in As(III) removal kinetics
      and mechanisms between dispersed zero-valent iron (d-ZVI) and resin-supported
      zero-valent iron (D201-ZVI) in the presence of dissolved oxygen and hydrogen
      peroxide. Experimental results show that As(III) could be removed by all the
      studied systems (d-ZVI/O2, d-ZVI/H2O2, D201-ZVI/O2, D201-ZVI/H2O2). The d
      ZVI/H2O2 system was more efficient than D201-ZVI/H2O2 for the oxidation of
      As(III). Similar trends were observed in O2 system for both solids. The kinetic
      behaviors as well as the influence of a hydroxyl radical scavenger (2-propanol)
      on the oxidation of As(III) at different pH suggest that the oxidation of As(III)
      in the d-ZVI/O2 and d-ZVI/H2O2 systems occurred mainly through Fenton-like
      reactions. The oxidation of As(III) in the D201-ZVI/O2 and D201-ZVI/H2O2 systems
      might be expected as follows: As(III) was firstly adsorbed onto the surface of
      the D201-ZVI, and then oxidation may proceed mainly through a non-Fenton
      mechanism that directly converts H2O2 into O2 and H2O. In addition, certain iron
      oxides in the D201-ZVI could also serve as oxidants for As(III) oxidation. The
      significant differences between the dispersed and supported ZVIs suggest that the
      supporting matrix interfered in the removal process, which deserves a further
      investigation. 

PMID- 24910052
TI  - Enhanced adsorption and desorption of VOCs vapor on novel micro-mesoporous
      polymeric adsorbents.
AB  - To enhance adsorption and desorption efficiency of volatile organic compounds
      from gas streams, we synthesized a series of well-developed micro-mesoporous
      hypercrosslinked polymeric adsorbents (MM-1, MM-2, and MM-3). The adsorption and
      desorption performance of dichloromethane and 2-butanone on newly synthesized
      adsorbents was investigated and compared with commercial micropore-dominated
      hypercrosslinked polymeric adsorbent (JT-001). The contributions of micropore and
      mesopore to adsorption and desorption of dichloromethane and 2-butanone on
      polymeric adsorbents were well elucidated. Consequently, the adsorbent MM-3 had
      been sorted out with high BET surface area (1606 m(2)/g), large micropore and
      mesopore volumes (0.562 mL/g and 1.046 mL/g, respectively). The MM-3 exhibited
      the similar adsorption capacities with JT-001 for dichloromethane and 2-butanone
      at regions of p/p0<0.2, but had higher adsorption capacities than JT-001 at high
      relative pressures. The largest adsorption capacities of MM-3 for dichloromethane
      and 2-butanone at 308 K were 1345.3 mg/g and 853.5 mg/g, respectively, which are
      about 1.78 and 1.88 times those of JT-001 under the same condition. Furthermore,
      the MM-3 exhibited higher desorption efficiencies than JT-001, especially for 2
      butanone with a higher boiling point.

PMID- 24910053
TI  - Propagation-of-uncertainty from contact angle and streaming potential
      measurements to XDLVO model assessments of membrane-colloid interactions.
AB  - Membrane fouling assessed from a fundamental standpoint within the context of the
      Derjaguin-Landau-Verwey-Overbeek (DLVO) model. The DLVO model requires that the
      properties of the membrane and foulant(s) be quantified. Membrane surface charge
      (zeta potential) and free energy values are characterized using streaming
      potential and contact angle measurements, respectively. Comparing theoretical
      assessments for membrane-colloid interactions between research groups requires
      that the variability of the measured inputs be established. The impact that such
      variability in input values on the outcome from interfacial models must be
      quantified to determine an acceptable variance in inputs. An interlaboratory
      study was conducted to quantify the variability in streaming potential and
      contact angle measurements when using standard protocols. The propagation of
      uncertainty from these errors was evaluated in terms of their impact on the
      quantitative and qualitative conclusions on extended DLVO (XDLVO) calculated
      interaction terms. The error introduced into XDLVO calculated values was of the
      same magnitude as the calculated free energy values at contact and at any given
      separation distance. For two independent laboratories to draw similar
      quantitative conclusions regarding membrane-foulant interfacial interactions the
      standard error in contact angle values must be?2.5 degrees , while that for the
      zeta potential values must be?7 mV.

PMID- 24910054
TI  - Passivated gel electrophoresis of charged nanospheres by light-scattering video
      tracking.
AB  - Gel electrophoresis (gel-EP) has been used for decades to separate charged
      biopolymers, such as DNA, RNA, and proteins, yet propagation of other charged
      colloidal objects, such as nanoparticles, during gel-EP has been studied
      comparatively little. Simply introducing anionic nanoparticles, such as sulfate
      stabilized polystyrene nanospheres, in standard large-pore agarose gels commonly
      used for biomolecules does not automatically ensure propagation or size
      separation because attractive interactions can exist between the gel and the
      nanoparticles. Whereas altering the surfaces of the nanoparticles is a possible
      solution, here, by contrast, we show that treating a common type I-A low
      electroendoosmosis agarose gel with a passivation agent, such as poly
      (ethyleneglycol), enables charged nanoparticles to propagate through large-pore
      passivated gels in a highly reproducible manner. Moreover, by taking advantage of
      the significant optical scattering from the nanoparticles, which is not easily
      measurable for biopolymers, relative to scattering from the gel, we perform real
      time, light-scattering, video-tracking gel-EP. Continuous optical measurements of
      the propagation of bands of uniformly sized nanospheres in passivated gels
      provides the propagation distance, L, and velocity, v, as a function of time for
      different sphere radii, electric field strengths, gel concentrations, and
      passivation agent concentrations. The steady-state particle velocities vary
      linearly with applied electric field strength, E, for small E, but these
      velocities become non-linear for larger E, suggesting that strongly driven
      nanoparticles can become elastically trapped in the smaller pores of the gel,
      which act like blind holes, in a manner that thermal fluctuations cannot
      overcome. Based on this assumption, we introduce a simple model that fits the
      measured v(E) in both linear and non-linear regimes over a relevant range of
      applied voltages. 

PMID- 24910056
TI  - Synthesis of nanotitania decorated few-layer graphene for enhanced visible light
      driven photocatalysis.
AB  - We report a simple method for decorating carboxyl functionalized few-layer
      graphene with titania (TiO2) nanoparticles by sonication and stirring under room
      temperature. The nanocomposites showed a remarkable improvement in visible light
      driven photocatalysis. From Raman and XRD analysis the number of layers of
      graphene was found to be 3. The TiO2 decorated few-layer graphene (FLG) sheets
      were characterized by electron microscopy, Raman spectroscopy, infrared
      spectroscopy, XRD and UV-vis spectroscopy. Titania nanoparticles were uniformly
      decorated on FLG matrix. The incorporation of titania on FLG enhanced the visible
      light photocatalytic activity of titania, lowered the electron hole recombination
      and improved the electron hole mobility. The enhanced life time of the charge
      carriers was confirmed from the photocurrent measurements. Compared to bare TiO2
      nanoparticles the FLG-TiO2 nanocomposites exhibited rapid degradation of
      Rhodamine B (Rhd B) under solar radiation. It was found that adsorption of dye
      molecules and the rate of degradation have been greatly enhanced in the FLG
      decorated with TiO2. The rapid degradation of Rhd B using carboxyl functionalized
      FLG-TiO2 within 8 min under solar radiation and 20 min under 30 W UV tube with
      very low concentration (0.01 wt.%) of the photocatalyst is the highlight of the
      present report. The mechanism of degradation and charge separation ability of the
      nanocomposite are also explored.

PMID- 24910055
TI  - Acid-base properties and surface complexation modeling of phosphate anion
      adsorption by wasted low grade iron ore with high phosphorus.
AB  - The adsorption phenomena and specific reaction processes of phosphate onto wasted
      low grade iron ore with high phosphorus (WLGIOWHP) were studied in this work.
      Zeta potential and Fourier transform infrared spectroscopy (FTIR) analyses were
      used to elucidate the interaction mechanism between WLGIOWHP and aqueous
      solution. The results implied that the main adsorption mechanism was the
      replacement of surface hydroxyl groups by phosphate via the formation of inner
      sphere complex. The adsorption process was characterized by chemical adsorption
      onto WLGIOWHP. The non-electrostatic model (NEM) was used to simulate the surface
      adsorption of phosphate onto WLGIOWHP. The total surface site density and
      protonation constants for NEM (N(T)=1.6*10(-4) mol/g, K(a1)=2.2*10(-4),
      K(a2)=6.82*10(-9)) were obtained by non-linear data fitting of acid-base
      titrations. In addition, the NEM was used to establish the surface adsorption
      complexation modeling of phosphate onto WLGIOWHP. The model successfully
      predicted the adsorption of phosphate onto WLGIOWHP from municipal wastewater.

PMID- 24910057
TI  - Lignocellulosic-derived modified agricultural waste: development,
      characterisation and implementation in sequestering pyridine from aqueous
      solutions.
AB  - The development and characterisation of modified agricultural waste (MAW) by
      H3PO4 activation is addressed in this study for sequestering pyridine from
      aqueous solutions. The adsorbent is characterised by carbon, hydrogen and
      nitrogen content of 55.53%, 3.28% and 0.98% respectively. The adsorbent also
      shows acidic (carboxylic, lactonic, phenolic groups) and basic carbon surface
      functionalities, functional groups viz. hydroxyl, carboxylic acid and bounded
      water molecules, BET surface area of 1254.67 m(2) g(-1), heterogeneous surface
      morphology and graphite like XRD patterns. Adsorption of pyridine is executed to
      evaluate the adsorptive uptake in batch (q(e)=107.18 mg g(-1)) as well as in
      column system (q(e)=140.94 mg g(-1)). The adsorption process followed the pseudo
      second-order kinetics with the Langmuir isotherm best representing the
      equilibrium adsorption data. The thermodynamic parameters (DeltaH(o)=9.39 kJ mol(
      1), DeltaG(o)=-5.99 kJ mol(-1), DeltaS(o)=50.76 J K(-1) mol(-1)) confirm the
      endothermic and spontaneous nature of the adsorption process with increase in
      randomness at solid/solution interface. The adsorption mechanism is governed by
      electrostatic and pi-pi dispersive interactions as well as by a two stage
      diffusion phenomena. Thermally regenerated spent MAW exhibited better adsorption
      efficiency for five adsorption-desorption cycles than chemically regenerated. The
      low-cost of MAW (USD 10.714 per kg) and favourable adsorption parameters
      justifies its use in the adsorptive removal of pyridine.

PMID- 24910058
TI  - Microwave-assisted synthesis of water soluble thiol capped CdSe/ZnS quantum dots
      and its interaction with sulfonylurea herbicides.
AB  - A simple and fast procedure for water solubilization of CdSe/ZnS quantum dots
      (QDs) using microwave irradiation (MW) has been optimized. The CdSe/ZnS QDs were
      synthesized in organic media and water solubilization was achieved by replacing
      the initial hydrophobic ligands (TOPO and TOP) with hydrophilic
      heterobifunctional thiol ligands, such as L-cysteine (L-Cys), 3-mercaptopropionic
      acid (3-MPA) and cysteamine (CTAM). The use of MW irradiation allowed carrying
      out the modification of the surface thiol of QDs in a simple and fast way (only
      40 s was required). Different optimization studies based on activation-time,
      irradiation-time, concentration of ligands, pH and lifetime fluorescent
      properties were carried out in order to obtain the best results for the
      solubilization of QDs. By the proposed method, the resulting water-soluble QDs
      exhibit a strong fluorescence emission at about 590 nm, with a high and
      reproducible photostability and acceptable yields. With the aim of contributing
      to exploiting the advantages of synthetized QDs from an analytical point of view,
      the different behavior with sulfonylurea herbicides (SUHs) were studied.

PMID- 24910059
TI  - Adsorption and nanowear properties of bovine submaxillary mucin films on solid
      surfaces: influence of solution pH and substrate hydrophobicity.
AB  - The adsorption and mechanical stability of bovine submaxillary mucins (BSM) films
      at solid-liquid interfaces were studied with respect to both substrate
      hydrophobicity and solution pH. Dynamic light scattering revealed a single peak
      distribution in neutral aqueous solution (pH 7.4) and a small fraction with
      enhanced aggregation was observed in acidic solution (pH 3.8). Both substrate
      hydrophobicity and solution pH were found to affect the spontaneous adsorption of
      BSM onto solid surfaces; BSM adsorbed more onto hydrophobic surfaces than
      hydrophilic ones, and adsorbed more at pH 3.8 than at pH 7.4. Thus, the highest
      "dry" adsorbed mass was observed for hydrophobic surfaces in pH 3.8 solution.
      However, a highest "wet" adsorbed mass, i.e. which includes the solvent coupled
      to the film, was observed for hydrophobic surfaces at pH 7.4. The mechanical
      stability of the films was studied at the nanoscale with an atomic force
      microscope operated in the friction force spectroscopy mode. Results revealed
      that BSM films formed on hydrophobic substrates were stronger than those formed
      on hydrophilic ones. Moreover, the film stability also depended on the ambient pH
      and stronger films were formed at acidic conditions, i.e. close to the BSM
      isoelectric point. 

PMID- 24910060
TI  - Synthesis of core-shell structured zeolite-A@mesoporous silica composites for
      butyraldehyde adsorption.
AB  - A simple sol-gel process is followed to construct a thin layer of mesoporous
      silica shell core-shell structure on micrometer sized and nanometer sized zeolite
      A (micro-zeolite A@SiO2 and nano-zeolite A@SiO2 respectively). Further thickness
      of the silica shells has been tuned from 20 to 50 nm while the zeolite A particle
      size changes from nanometer to micrometer. Pores of the silica shells arranged
      orderly on the crystal-faces of zeolite-A cores. Typically, adsorption amount of
      the butyraldehyde towards these core-shell composite materials is investigated
      well and is verified to be almost double than that of the pristine zeolite A.
      Interestingly the nano-zeolite A core containing core-shell composite absorbs
      maximum butyraldehyde (314 mg/g) compared to the micro-zeolite A (266 mg/g), even
      if the mesoporous shell thickness of the nano-zeolite A@SiO2 composites is less
      (20 nm) than that of micro-zeolite A@SiO2 (50 nm). Both of these values are
      significantly larger than the pristine zeolite A (nano-zeolite A; 151 mg/g and
      micro-zeolite A; 146 mg/g).

PMID- 24910061
TI  - Adsorption of ions at the interface oil|aqueous electrolyte and at interfaces
      with adsorbed alcohol.
AB  - We investigate the applicability of the Schmutzer's model for three types of
      interfaces: aqueous electrolyte|alkane, aqueous electrolyte|long chained alcohol
      phase, and aqueous electrolyte|alkane with adsorbed alcohol. The model predicts a
      strong decrease of the electrolyte desorption at water|alcohol interface in
      comparison with water|alkane, in quantitative agreement with the tensiometric
      data. The effect is related to the penetration of the alcohol -OH group into the
      surface layer of the aqueous solution. The same model predicts a decrease with
      the electrolyte concentration of the chemical potential of the alcohol molecules
      adsorbed at the water|oil interface, which results in an increase of the
      adsorption activity of oil-soluble alcohols, again in quantitative agreement with
      the experiment. The analysis of the deviations of Schmutzer's model predictions
      from the experimental data for large polarizable anions allows making qualitative
      conclusions for the magnitude of the ion-specific hydrophobic and dispersion
      forces at water|gas and water|oil interfaces. 

PMID- 24910062
TI  - Self-assembly of new surface active ionic liquids based on Aerosol-OT in aqueous
      media.
AB  - New anionic ionic liquid surfactants have been synthesized by replacing the
      sodium cation of Aerosol-OT (sodium dioctylsulfosuccinate, [Na]AOT) with various
      biocompatible moieties, such as 1-butyl-3-methyl imidazolium ([C4mim]),
      proliniumisopropylester ([ProC3]), cholinium ([Cho]), and guanidinium ([Gua]).
      The Aerosol-OT derived ionic liquids (AOT-ILs) were found fairly soluble in water
      and formed vesicles above a critical vesicle concentration (CVC) which depended
      upon the nature of cation, and followed the order:
      [ProC3]<[C4mim]<[Gua]<[Cho]<Na(+). The self-assembly process was characterized
      using surface tension (ST), isothermal titration calorimetry (ITC), conductivity,
      dynamic light scattering (DLS), nuclear magnetic resonance (NMR) and transmission
      electron microscopy (TEM). Unlike other AOT-ILs, a structural transformation has
      been observed for [C4mim]AOT above CVC, because of certain amphiphilic character
      in the cation [C4mim]. Thermodynamic parameters calculated from ITC and
      conductivity techniques revealed that the vesicle formation process is entropy
      driven for [C4mim]AOT, whereas the process is both enthalpy and entropy driven
      for other AOT-ILs. In order to check the versatility of synthesized AOT-ILs we
      have tested their dissolution behavior in a different class of ionic liquids. All
      the AOT-ILs were found fairly soluble in the hydrophilic IL, ethanolammonium
      formate (EOAF), whereas only [C4mim]AOT and [ProC3]AOT were found soluble in
      hydrophobic IL, [C4mim]Tf2N. Such combinations can have potential for
      construction of stable colloidal formulations or microemulsions in ionic liquid
      media. 

PMID- 24910063
TI  - Effects of chemical structure on the dynamic and static surface tensions of short
      chain, multi-arm nonionic fluorosurfactants.
AB  - Fluorinated surfactants with short perfluoroalkyl chains (R(F)) as potential
      substitutes for the environmentally questionable, long R(F) systems are
      presented. Three types of nonionic hydrophilic-fluorophilic amphiphiles are
      synthesized and evaluated based on surface activity in equilibrated (static) and
      non-equilibrated (dynamic) states. Furthermore, several mono- and disaccharide
      based fluorosurfactants are also examined as potential non-bioaccumulative
      alternatives. A correlation between the chemical structure and resulting surface
      properties is made by comparing R(F) length, number and size, alkyl-spacer, and
      hydrophilic moieties. Based on dynamic and static surface tension experiments,
      the effects of surfactant structure are summarized to provide a basis for the
      future design of fluorosurfactants. We have found that surfactants with more
      perfluorinated chains tend to have a higher surface tension reduction, but
      typically result in slower dynamic behaviors. Using the presented structural
      characteristics, surfactants with R(F)<4 can be prepared with static surface
      tensions as low as 18.1 mN/m or reduce surface tension within milliseconds.

PMID- 24910064
TI  - Physicochemical characterization of solid lipid nanoparticles (SLNs) prepared by
      a novel microemulsion technique.
AB  - HYPOTHESIS: Solid lipid nanoparticles (SLNs) produced by conventional
      microemulsion techniques using thermal heat have specific limitations (e.g. high
      polydispersity, instability and low encapsulation). Replacing thermal heat with
      microwave heat may produce SLNs which overcome some of these limitations.
      EXPERIMENTS: Stearic acid-based SLNs prepared with Tween(r) 20 as the emulsifier
      were chosen as the optimum formulation to encapsulate and potentially deliver the
      antibacterial drug tetracycline. All formulations were characterized for their
      particle size, zeta potential, encapsulation efficiency, loading capacity,
      thermal and X-ray diffraction analyses. Short-term stability and in vitro drug
      studies were also performed. FINDINGS: Microwave heating helps to overcome
      several disadvantages associated with thermal heating (nonuniform, inefficient
      and slow) and results in improved particle characteristics. There is thus the
      potential for new opportunities in the development of colloidal carriers. The
      particle sizes of microwave-produced SLNs were in the desired nanometer range
      (200-250 nm) with both lower size and lower polydispersity than the conventional
      SLNs. We take this as an indication of improved stability; however zeta potential
      measurements were not different, indicating similar stability. True stability
      testing (visual observation with time) did show that the microwave-induced SLNs
      were found to be more stable, particularly when refrigerated. The microwave
      produced SLNs also demonstrated improved encapsulation efficiency and loading
      capacity. Thermal and diffraction analysis confirmed a lowered crystallinity of
      stearic acid with successful incorporation of tetracycline into the SLNs. In
      vitro release studies indicated that, after an initial burst release, SLNs could
      provide prolonged release of tetracycline. The presence of tetracycline and non
      toxicity of carriers towards microbes was confirmed by antimicrobial
      susceptibility tests.

PMID- 24910065
TI  - Efficient removal of cesium from aqueous solution with vermiculite of enhanced
      adsorption property through surface modification by ethylamine.
AB  - Ethylamine modified vermiculite (Ethyl-VER) with high specific surface area and
      excellent pore structure was prepared to remove cesium from aqueous solution. The
      physic-chemical properties of the pristine and modified vermiculite were analyzed
      by X-ray diffraction (XRD), Fourier-transform infrared (FTIR), specific surface
      area (BET) and scanning electron microscopy/energy disperse spectroscopy
      (SEM/EDS). The corroding effect of ethylamine increased the specific surface area
      of vermiculite from 4.35 to 15.59 m(2) g(-1), and the average pore diameter
      decreased from 6.8 to 5.34 nm. Batch adsorption experiments were conducted as a
      function of pH, initial Cs(+) concentration, contact time, coexisting cations
      (K(+), Na(+), Ca(2+)) and low-molecular-weight organic acids (acetic acid, oxalic
      acid, citric acid) to illustrate the adsorption behavior. The study found that
      the adsorption capacity of cesium in aqueous solution was improved from 56.92 to
      78.17 mg g(-1) after modification. The formation of micropores and mesopores and
      the increased surface area played a critical role in the enhancement of cesium
      adsorption. Kinetic experiments indicated that the adsorption process can be
      simulated well with a pseudo-second-order model. The presence of cations or low
      molecular-weight organic acids inhibited cesium adsorption in different degrees.
      On the basis of our results, Ethyl-VER with good surface characteristics and high
      adsorption capacity is a suitable adsorbent for cesium removal from aqueous
      solution.

PMID- 24910066
TI  - Functional kaolinite supported Fe/Ni nanoparticles for simultaneous catalytic
      remediation of mixed contaminants (lead and nitrate) from wastewater.
AB  - Kaolinite supported bimetallic Fe/Ni nanoparticles (K-Fe/Ni) demonstrated
      capacity for simultaneous removal of both cationic and anionic contaminants such
      as Pb (II) and NO3(-). The dispersion of Fe/Ni nanoparticles was improved when
      kaolinite was used as a stabilizer, and also enhanced the reactivity of K-Fe/Ni.
      The adsorption of Pb (II) onto the kaolinite and the consequent simultaneous
      catalytic reduction of Pb (II) and NO3(-) kaolinite were confirmed by SEM, BET,
      EDS, XRD and batch adsorption-reduction test. Orthogonal method showed that
      initial concentrations of Pb (II) and NO3(-), as well the dosage of K-Fe/Ni
      showed the most significant impact on the removal rates, where 86.3% of Pb (II)
      and 73.6% of NO3(-) was removed at optimized conditions. In addition, K-Fe/Ni
      could be stored for 15 days in dry air without losing reactivity. Reusability
      test of K-Fe/Ni indicated that the removal efficiency decreased by 12.5% for Pb
      (II) and 27.2% for NO3(-) after using 3 times successively. Two electroplating
      wastewater samples were tested and showed K-Fe/Ni could remove more than 96% of
      Pb (II) and NO3(-) under the optimized conditions.

PMID- 24910067
TI  - Influence of the finite size and effective permittivity of ions on the
      equilibrium double layer around colloidal particles in aqueous electrolyte
      solution.
AB  - The equilibrium properties of the electrical double layer surrounding a charged
      spherical colloidal particle immersed in an aqueous electrolyte solution are
      examined taking into account the finite ion size. This study includes the
      representation of the steric interactions among ions using both the Bikerman and
      the Carnahan-Starling models, an account of all the effects related to the
      representation of hydrated ions as dielectric spheres (dependence of the
      electrolyte solution permittivity, on the local ion concentration, and appearance
      of the Born and the dielectrophoretic forces acting on the ions), and solution of
      the problem for both high and low surface charge values. We find that the
      Carnahan-Starling model together with effective ion permittivity related effects
      appears to be able to provide an interpretation to the electrokinetic potential
      vs. surface charge dependence in the case of colloidal particles suspended in
      aqueous electrolyte solutions. On the contrary, for electrode-electrolyte
      systems, both the Bikerman and the Carnahan-Starling models might be able to
      explain this dependence. 

PMID- 24910068
TI  - SAXS reveals the magnetic alignment pathway of the goethite columnar liquid
      crystal phase.
AB  - The alignment of board-like colloidal goethite particles in the dense rectangular
      centred columnar liquid crystal phase in an external magnetic field is studied
      using small angle X-ray scattering (SAXS). Transient SAXS-patterns show
      broadening of the columnar reflections in specific directions. While the
      reflections along the field stay at a constant Q-value, the other reflections do
      not. These results imply a certain pathway of reorientation. It appears that
      alignment proceeds via collective rotation of domains inducing 'nanoshear'
      between the layers of particles, which slide over each other. The results support
      the recently suggested martensitic transition pathway for the simple and centred
      rectangular columnar phases, which were found to spontaneously transform into
      each other in another goethite system. The results also provide a fine example of
      how SAXS can be used to study reorientation behaviour of liquid crystals at the
      nanoscale. 

PMID- 24910069
TI  - A single-cell imaging screen reveals multiple effects of secreted small molecules
      on bacteria.
AB  - Bacteria cells exist in close proximity to other cells of both the same and
      different species. Bacteria secrete a large number of different chemical species,
      and the local concentrations of these compounds at the surfaces of nearby cells
      may reach very high levels. It is fascinating to imagine how individual cells
      might sense and respond to the complex mix of signals at their surface. However,
      it is difficult to measure exactly what the local environmental composition looks
      like, or what the effects of individual compounds on nearby cells are. Here, an
      electron microscopy imaging screen was designed that would detect morphological
      changes induced by secreted small molecules. This differs from conventional
      approaches by detecting structural changes in individual cells rather than gene
      expression or growth rate changes at the population level. For example, one of
      the changes detected here was an increase in outer membrane vesicle production,
      which does not necessarily correspond to a change in gene expression. This
      initial study focussed on Pseudomonas aeruginosa, Escherichia coli, and
      Burkholderia dolosa, and revealed an intriguing range of effects of secreted
      small molecules on cells both within and between species. 

PMID- 24910070
TI  - Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early
      and late IC-ERP amplitudes during face recognition.
AB  - Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal
      resolution of functional brain studies. However, this method usually suffers from
      poor EEG quality, especially for evoked potentials (ERPs), due to specific
      artifacts. As such, the use of EEG-informed fMRI analysis in the context of
      cognitive studies has particularly focused on optimizing narrow ERP time windows
      of interest, which ignores the rich diverse temporal information of the EEG
      signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural
      cascade occurring during face recognition in 14 healthy volunteers by using the
      successive ERP peaks recorded during the cognitive part of this process. N170,
      N400 and P600 peaks, commonly associated with face recognition, were successfully
      and reproducibly identified for each trial and each subject by using a group
      independent component analysis (ICA). For the first time we use this group ICA to
      extract several independent components (IC) corresponding to the sequence of
      activation and used single-trial peaks as modulation parameters in a general
      linear model (GLM) of fMRI data. We obtained an occipital-temporal-frontal stream
      of BOLD signal modulation, in accordance with the three successive IC-ERPs
      providing an unprecedented spatio-temporal characterization of the whole
      cognitive process as defined by BOLD signal modulation. By using this approach,
      the pattern of EEG-informed BOLD modulation provided improved characterization of
      the network involved than the fMRI-only analysis or the source reconstruction of
      the three ERPs; the latter techniques showing only two regions in common
      localized in the occipital lobe. 

PMID- 24910072
TI  - Professional training in creative writing is associated with enhanced fronto
      striatal activity in a literary text continuation task.
AB  - The aim of the present study was to explore brain activities associated with
      creativity and expertise in literary writing. Using functional magnetic resonance
      imaging (fMRI), we applied a real-life neuroscientific setting that consisted of
      different writing phases (brainstorming and creative writing; reading and copying
      as control conditions) to well-selected expert writers and to an inexperienced
      control group. During creative writing, experts showed cerebral activation in a
      predominantly left-hemispheric fronto-parieto-temporal network. When compared to
      inexperienced writers, experts showed increased left caudate nucleus and left
      dorsolateral and superior medial prefrontal cortex activation. In contrast, less
      experienced participants recruited increasingly bilateral visual areas. During
      creative writing activation in the right cuneus showed positive association with
      the creativity index in expert writers. High experience in creative writing seems
      to be associated with a network of prefrontal (mPFC and DLPFC) and basal ganglia
      (caudate) activation. In addition, our findings suggest that high verbal
      creativity specific to literary writing increases activation in the right cuneus
      associated with increased resources obtained for reading processes. 

PMID- 24910071
TI  - Reversal of cortical information flow during visual imagery as compared to visual
      perception.
AB  - The role of bottom-up and top-down connections during visual perception and the
      formation of mental images was examined by analyzing high-density EEG recordings
      of brain activity using two state-of-the-art methods for assessing the
      directionality of cortical signal flow: state-space Granger causality and dynamic
      causal modeling. We quantified the directionality of signal flow in an occipito
      parieto-frontal cortical network during perception of movie clips versus mental
      replay of the movies and free visual imagery. Both Granger causality and dynamic
      causal modeling analyses revealed an increased top-down signal flow in parieto
      occipital cortices during mental imagery as compared to visual perception. These
      results are the first direct demonstration of a reversal of the predominant
      direction of cortical signal flow during mental imagery as compared to
      perception. 

PMID- 24910073
TI  - Early pregnancy agricultural pesticide exposures and risk of gastroschisis among
      offspring in the San Joaquin Valley of California.
AB  - BACKGROUND: Prevalence of gastroschisis has inexplicably been increasing over the
      past few decades. Our intent was to explore whether early gestational exposures
      to pesticides were associated with risk of gastroschisis. METHODS: We used
      population-based data, accompanied by detailed information from maternal
      interviews as well as information on residential proximity to a large number of
      commercial pesticide applications during early pregnancy. The study population
      derived from the San Joaquin Valley of California (). Cases were 156
      infants/fetuses with gastroschisis and controls were 785 infants without birth
      defects. RESULTS: Among 22 chemical pesticide groups analyzed, none had an
      elevated odds ratio with an associated confidence interval that excluded 1.0,
      although exposure to the triazine group showed borderline significance. Among 36
      specific pesticide chemicals analyzed, only exposure to petroleum distillates was
      associated with an elevated risk, odds ratio = 2.5 (1.1-5.6). In general, a
      substantially different inference was not derived when analyses were stratified
      by maternal age or when risk estimation included adjustment for race/ethnicity,
      body mass index, folic acid supplement use, and smoking. CONCLUSION: Our study
      rigorously adds to the scant literature on this topic. Our a priori expectation
      was that we would observe certain pesticide compounds to be particularly
      associated with young age owing to the disproportionate risk observed for young
      women to have offspring with gastroschisis. We did not observe an exposure
      profile unique to young women.

PMID- 24910075
TI  - A novel papillomavirus isolated from a nasal neoplasia in an Italian free-ranging
      chamois (Rupicapra r. rupicapra).
AB  - Most amniotes are the hosts of many, distantly related papillomaviruses (PVs).
      Infection by PVs can be asymptomatic, or lead instead to benign or malignant
      lesions. However, PVs infecting animals and associated with malignancies are
      still largely understudied. In the present study, we communicate the complete
      genome of a novel PV found in a nasal neoplasia of a free-ranging alpine chamois
      (Rupicapra r. rupicapra) in an Italian national park. Long-PCR and cloning
      approaches followed for Sanger sequencing were used to identify the first PV
      found in chamois. The genome of the novel virus - RrupPV1 - of 7256 bp in length,
      presents the classical PV structure, and lacks the interE2-L2 region that hosts
      the E5 gene in AlphaPVs and in DeltaPVs. The nucleotide identity percentage of
      the L1 ORF, places RrupPV1 together with OaPV3 in the same genus. The latter is a
      PV isolated from a squamous cell carcinoma in sheep in Sardinia. Full-genome
      phylogenetic reconstructions suggest that these two viruses are sister taxa, and
      that both of them are very distantly related to any other known PV. Many
      cetartiodactyl species are infected by non-monophyletic PVs. Our results
      exemplify further the multiple links between the infection by certain, distantly
      related PVs and the development of diverse cancers in animals and highlight the
      need of a systematic search of oncogenic and non-oncogenic animal PVs.

PMID- 24910074
TI  - The influence of different cellular environments on PET radioligand binding: an
      application to D2/3-dopamine receptor imaging.
AB  - Various D2/3 receptor PET radioligands are sensitive to endogenous dopamine
      release in vivo. The Occupancy Model is generally used to interpret changes in
      binding observed in in vivo competition binding studies; an Internalisation
      Hypothesis may also contribute to these changes in signal. Extension of in vivo
      competition imaging to other receptor systems has been relatively unsuccessful. A
      greater understanding of the cellular processes underlying signal changes
      following endogenous neurotransmitter release may help translate this imaging
      paradigm to other receptor systems. To investigate the Internalisation Hypothesis
      we assessed the effects of different cellular environments, representative of
      those experienced by a receptor following agonist-induced internalisation, on the
      binding of three D2/3 PET ligands with previously reported sensitivities to
      endogenous dopamine in vivo, namely [3H]spiperone, [3H]raclopride and [3H]PhNO.
      Furthermore, we determined the contribution of each cellular compartment to total
      striatal binding for these D2/3 ligands. These studies suggest that sensitivity
      to endogenous dopamine release in vivo is related to a decrease in affinity in
      the endosomal environment compared with those found at the cell surface. In
      agreement with these findings we also demonstrate that ~25% of total striatal
      binding for [3H]spiperone originates from sub-cellular, microsomal receptors,
      whereas for [3H]raclopride and [3H]PhNO, this fraction is lower, representing
      ~14% and 17%, respectively. This pharmacological approach is fully translatable
      to other receptor systems. Assessment of affinity shifts in different cellular
      compartments may play a crucial role for understanding if a radioligand is
      sensitive to endogenous release in vivo, for not just the D2/3, but other
      receptor systems.

PMID- 24910076
TI  - In situ assessment of the contact angles of nanoparticles adsorbed at fluid
      interfaces by multiple angle of incidence ellipsometry.
AB  - Here multiple angle of incidence ellipsometry was successfully applied to in situ
      assess the contact angle and surface coverage of gold nanoparticles as small as
      18 nm, coated with stimuli-responsive polymers, at water-oil and water-air
      interfaces in the presence of NaCl and NaOH, respectively. The interfacial
      adsorption of the nanoparticles was found to be very slow and took days to reach
      a fairly low surface coverage. For water-oil interfaces, in situ nanoparticle
      contact angles agree with the macroscopic equilibrium contact angles of planar
      gold surfaces with the same polymer coatings, whilst for water-air interfaces,
      significant differences have been observed. 

PMID- 24910077
TI  - High-fidelity reproduction of spatiotemporal visual signals for retinal
      prosthesis.
AB  - Natural vision relies on spatiotemporal patterns of electrical activity in the
      retina. We investigated the feasibility of veridically reproducing such patterns
      with epiretinal prostheses. Multielectrode recordings and visual and electrical
      stimulation were performed on populations of identified ganglion cells in
      isolated peripheral primate retina. Electrical stimulation patterns were designed
      to reproduce recorded waves of activity elicited by a moving visual stimulus.
      Electrical responses in populations of ON parasol cells exhibited high spatial
      and temporal precision, matching or exceeding the precision of visual responses
      measured in the same cells. Computational readout of electrical and visual
      responses produced similar estimates of stimulus speed, confirming the fidelity
      of electrical stimulation for biologically relevant visual signals. These results
      suggest the possibility of producing rich spatiotemporal patterns of retinal
      activity with a prosthesis and that temporal multiplexing may aid in reproducing
      the neural code of the retina. 

PMID- 24910079
TI  - Nanoparticle albumin-bound paclitaxel can be useful agent to advanced primary
      mucinous carcinoma of the skin.

PMID- 24910080
TI  - Identification of toluene degraders in a methanogenic enrichment culture.
AB  - Methanogenic biodegradation involves the cooperative metabolism of syntrophic
      bacteria that catalyse the initial attack and subsequent degradation of
      hydrocarbons, and methanogens that convert intermediates such as hydrogen and
      carbon dioxide, formate, and/or acetate to methane. The identity of syntrophic
      microbes and the nature of their interactions with other syntrophs and
      methanogens are not well understood. Furthermore, it is difficult to isolate the
      organisms responsible for the initial activation and subsequent degradation of
      hydrocarbon substrates under methanogenic conditions due to the thermodynamic
      relationships that exist among microbes in methanogenic communities. We used time
      resolved RNA stable isotope probing and RT-qPCR to identify the organisms
      involved in the initial attack on toluene and subsequent degradation reactions in
      a highly enriched toluene-degrading methanogenic culture. Our results reveal the
      importance of a Desulfosporosinus sp. in anaerobic toluene activation in the
      culture. Other organisms that appear to play roles in toluene degradation include
      Syntrophaceae, Desulfovibrionales and Chloroflexi. The high bacterial diversity
      observed in this culture and the extensive labelling of different phylogenetic
      groups over the course of the stable isotope probing experiment highlight the
      complexity of the relationships that exist in methanogenic ecosystems. 

PMID- 24910081
TI  - A 25 years experience of group-housed sows-reproduction in animal welfare
      friendly systems.
AB  - Since January 1 2013, group housing of sows has been compulsory within the
      European Union (EU) in all pig holdings with more than ten sows. Sows and gilts
      need to be kept in groups from 4 weeks after service to 1 week before the
      expected time of farrowing (Article 3(4) of Directive 2008/120/EC on the
      protection of pigs). The legislation regarding group housing was adopted already
      in 2001 and a long transitional period was allowed to give member states and
      producers enough time for adaptation. Even so, group housing of sows still seems
      to be uncommon in the EU, and is also uncommon in commercial pig farming systems
      in the rest of the world. In this review we share our experience of the Swedish
      25 years of animal welfare legislation stipulating that sows must be loose-housed
      which de facto means group housed. The two most important concerns related to
      reproductive function among group-housed sows are the occurrence of lactational
      oestrus when sows are group-housed during lactation, and the stress that is
      associated with group housing during mating and gestation. Field and clinical
      observations in non-lactating, group-housed sows in Sweden suggest that by making
      basic facts known about the pig reproductive physiology related to mating, we
      might achieve application of efficient batch-wise breeding without
      pharmacological interventions. Group housing of lactating sows has some
      production disadvantages and somewhat lower productivity would likely have to be
      expected. Recordings of behavioural indicators in different housing systems
      suggest a lower welfare level in stalled animals compared with group-housed ones.
      However, there are no consistent effects on the reproductive performance
      associated with different housing systems. Experimental studies suggest that the
      most sensitive period, regarding disturbance of reproductive functions by
      external stressors, is the time around oestrus. We conclude that by keeping sows
      according to the pig welfare-friendly Directive 2008/120/EC, it is possible to
      combine group-housing of sows with good reproductive performance and
      productivity. However, substantially increased research and development is needed
      to optimize these systems. 

PMID- 24910082
TI  - Outcome of children [corrected] with heart murmurs referred from general practice
      to a paediatrician with expertise in cardiology.
AB  - BACKGROUND: Heart murmurs are common in children. The majority are detected
      incidentally, and congenital heart disease is rare. There are no published United
      Kingdom guidelines for management of children with murmurs in primary care.
      Common practice is to refer all children for specialist assessment. AIM: To
      review outcomes of children with heart murmurs who were referred by general
      practitioners to a clinic conducted by a paediatrician with expertise in
      cardiology. Design and setting A retrospective review of children referred by
      general practitioners to a paediatrician with expertise in cardiology. METHODS:
      Hospital records of all children under 17 years of age who attended the clinic
      during 2011 were reviewed. We excluded children previously seen by any cardiology
      service. RESULTS: There were 313 new primary care referrals, with complete
      records available for 310 children. Of them, 186 (60%) were referred with a
      murmur: 154 for an asymptomatic murmur alone, and 32 for a murmur plus additional
      symptoms or family history of congenital heart disease. All underwent
      echocardiography. Of the patients, 38 (20%) had congenital heart disease. Younger
      children were more likely to have congenital heart disease. There was no
      difference between rates of congenital heart disease in children with or without
      symptoms or a family history. CONCLUSION: The finding that a large proportion of
      children referred by general practitioners with asymptomatic heart murmurs have
      congenital heart disease supports current referral practice on clinical grounds.

PMID- 24910078
TI  - Hippocampal representation of related and opposing memories develop within
      distinct, hierarchically organized neural schemas.
AB  - Recent evidence suggests that the hippocampus may integrate overlapping memories
      into relational representations, or schemas, that link indirectly related events
      and support flexible memory expression. Here we explored the nature of
      hippocampal neural population representations for multiple features of events and
      the locations and contexts in which they occurred. Hippocampal networks developed
      hierarchical organizations of associated elements of related but separately
      acquired memories within a context, and distinct organizations for memories where
      the contexts differentiated object-reward associations. These findings reveal
      neural mechanisms for the development and organization of relational
      representations.

PMID- 24910083
TI  - Gender differences in presentation, management and inhospital outcome in patients
      with ST-segment elevation myocardial infarction: data from 5000 patients included
      in the ORBI prospective French regional registry.
AB  - BACKGROUND: Gender differences in presentation, management and outcome in
      patients with ST-segment elevation myocardial infarction (STEMI) have been
      reported. AIM: To determine whether female gender is associated with higher
      inhospital mortality. METHODS: Data from ORBI, a regional STEMI registry of 5
      years' standing, were analysed. The main data on presentation, management,
      inhospital outcome and prescription at discharge were compared between genders.
      Various adjusted hazard ratios were then calculated for inhospital mortality
      (women versus men). RESULTS: The analysis included 5000 patients (mean age 62.6+/
      13 years), with 1174 women (23.5%). Women were on average 8 years older than men,
      with more frequent co-morbidities. Median ischaemia time was 215 minutes (26
      minutes longer in women; P<0.05). Reperfusion strategies in women less frequently
      involved fibrinolysis, coronary angiography, radial access and thrombo
      aspiration. Female gender, especially in patients aged<60 years, was associated
      with poorer inhospital prognosis (including higher inhospital mortality: 9% vs.
      4% in men; P<0.0001), and underutilization of recommended treatments at
      discharge. Moreover, excess female inhospital mortality was independent of
      presentation, revascularization time and reperfusion strategy (hazard ratio for
      women 1.33, 95% confidence interval 1.01-1.76; P=0.04). CONCLUSIONS: One in four
      patients admitted for STEMI was female, with significant differences in
      presentation. Female gender was associated with less-optimal treatment, both in
      the acute-phase and at discharge. Efforts should be made to reduce these
      differences, especially as female gender was independently associated with an
      elevated risk of inhospital mortality.

PMID- 24910084
TI  - Relevant new insights into the effects of photoprotection in cutaneous lupus
      erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) denotes a heterogeneous spectrum of
      autoimmune diseases that primarily affect the skin. Ultraviolet irradiation (UV)
      is one of the most important environmental factors that can trigger skin lesions
      in CLE or even induce systemic organ manifestation. It has been shown that broad
      spectrum sunscreen with high sun protection factors can effectively prevent UV
      induced skin lesions in patients with different subtypes of CLE. In a recent
      issue of Experimental Dermatology, Zahn and colleagues demonstrate that potent
      photoprotection blocks disease-specific skin lesions in CLE patients by reducing
      lesional tissue damage and interferon-driven inflammation. 

PMID- 24910085
TI  - Fertility treatment and child intelligence, attention, and executive functions in
      5-year-old singletons: a cohort study.
AB  - OBJECTIVE: To assess the association of fertility treatment and subfertility with
      offspring intelligence, attention, and executive functions in 5-year-old
      singletons. DESIGN: Follow-up study. SETTING: Denmark 2003-2008. POPULATION: A
      cohort of 1782 children sampled from the Danish National Birth Cohort. METHODS:
      The children were tested with a neuropsychological battery at age five. In
      addition to tests of intelligence, attention and executive functions, the follow
      up included extensive information on important covariates. The analyses were
      conducted using multiple linear regression and adjusted for parental educational
      level, maternal intelligence, age, parity, body mass index, smoking in pregnancy,
      alcohol consumption in pregnancy and child gender, child age, and examiner. MAIN
      OUTCOME MEASURES: Wechsler Preschool and Primary Scale of Intelligence-Revised,
      the Test of Everyday Attention for Children at Five, and the Behavior Rating
      Inventory of Executive Functions scores. RESULTS: A consistent pattern of
      nonsignificantly lower scores were only observed for intelligence and executive
      functions in children born after fertility treatment or by subfertile parents
      when the results were unadjusted for maternal intelligence and parental
      educational level. When adjusted for these and other covariates, there were no
      significant mean differences in intelligence (mean difference -2.8, 95% CI -7.8,
      2.2), overall attention (-0.1, 95% CI -0.6, 0.3), or parent-rated executive
      functions (-0.1, 95% CI -3.0, 2.9) between children born after spontaneous
      conception and children born to parents conceiving after fertility treatment.
      Similarly, there were no significant mean differences in intelligence (mean
      difference 0.6, 95% CI -2.2, 3.4), overall attention (0.1, 95% CI -0.2, 0.4), or
      parent-rated executive functions (1.0, 95% CI -1.8, 3.7) between children born
      after spontaneous conception and children born to subfertile parents waiting more
      than 12 months before conceiving naturally. CONCLUSIONS: This study suggests that
      parental subfertility and fertility treatment are unrelated to offspring
      intelligence, attention and executive functions.

PMID- 24910086
TI  - Selenium and selenoproteins: an overview on different biological systems.
AB  - Selenium (Se) is an essential trace element for humans, plants and
      microorganisms. Inorganic selenium is present in nature in four oxidation states:
      selenate, selenite, elemental Se and selenide in decreasing order of redox
      status. These forms are converted by all biological systems into more
      bioavailable organic forms, mainly as the two seleno-amino acids selenocysteine
      and selenomethionine. Humans, plants and microorganisms are able to fix twhese
      amino acids into proteins originating Se-containing proteins by a simple
      replacement of methionine with selenomethionine, or "true" selenoproteins if the
      insertion of selenocysteine is genetically encoded by a specific UGA codon.
      Selenocysteine is usually present in the active site of enzymes, being essential
      for their catalytic activity. This review will focus on the strategies adopted by
      the different biological systems for selenium incorporation into proteins and on
      the importance of this element for the physiological functions of living
      organisms. The most known selenoproteins of humans and microorganisms will be
      listed highlighting the importance of this element and the problems connected
      with its deficiency. 

PMID- 24910088
TI  - Less is more: selective advantages can explain the prevalent loss of biosynthetic
      genes in bacteria.
AB  - Bacteria that have adapted to nutrient-rich, stable environments are typically
      characterized by reduced genomes. The loss of biosynthetic genes frequently
      renders these lineages auxotroph, hinging their survival on an environmental
      uptake of certain metabolites. The evolutionary forces that drive this genome
      degradation, however, remain elusive. Our analysis of 949 metabolic networks
      revealed auxotrophies are likely highly prevalent in both symbiotic and free
      living bacteria. To unravel whether selective advantages can account for the
      rampant loss of anabolic genes, we systematically determined the fitness
      consequences that result from deleting conditionally essential biosynthetic genes
      from the genomes of Escherichia coli and Acinetobacter baylyi in the presence of
      the focal nutrient. Pairwise competition experiments with each of 20 mutants
      auxotrophic for different amino acids, vitamins, and nucleobases against the
      prototrophic wild type unveiled a pronounced, concentration-dependent growth
      advantage of around 13% for virtually all mutants tested. Individually deleting
      different genes from the same biosynthesis pathway entailed gene-specific fitness
      consequences and loss of the same biosynthetic genes from the genomes of E. coli
      and A. baylyi differentially affected the fitness of the resulting auxotrophic
      mutants. Taken together, our findings suggest adaptive benefits could drive the
      loss of conditionally essential biosynthetic genes.

PMID- 24910087
TI  - A large genomic island allows Neisseria meningitidis to utilize propionic acid,
      with implications for colonization of the human nasopharynx.
AB  - Neisseria meningitidis is an important human pathogen that is capable of killing
      within hours of infection. Its normal habitat is the nasopharynx of adult humans.
      Here we identify a genomic island (the prp gene cluster) in N. meningitidis that
      enables this species to utilize propionic acid as a supplementary carbon source
      during growth, particularly under nutrient poor growth conditions. The prp gene
      cluster encodes enzymes for a methylcitrate cycle. Novel aspects of the
      methylcitrate cycle in N. meningitidis include a propionate kinase which was
      purified and characterized, and a putative propionate transporter. This genomic
      island is absent from the close relative of N. meningitidis, the commensal
      Neisseria lactamica, which chiefly colonizes infants not adults. We reason that
      the possession of the prp genes provides a metabolic advantage to N. meningitidis
      in the adult oral cavity, which is rich in propionic acid-generating bacteria.
      Data from classical microbiological and sequence-based microbiome studies provide
      several lines of supporting evidence that N. meningitidis colonization is
      correlated with propionic acid generating bacteria, with a strong correlation
      between prp-containing Neisseria and propionic acid generating bacteria from the
      genus Porphyromonas, and that this may explain adolescent/adult colonization by
      N. meningitidis. 

PMID- 24910089
TI  - Phosphofructokinase: a mediator of glycolytic flux in cancer progression.
AB  - In view of the current limitations of cancer chemotherapy, there has been
      resurgent interest in re-visiting glycolysis to determine whether tumors could be
      killed by energy deprivation rather than solely by strategies to inhibit
      proliferation. Cancer cells exhibit a uniquely high rate of glucose utilization,
      converting it into lactate whose export subsequently creates an acidic
      extracellular environment that is thought to promote invasion and metastasis, in
      preference to its complete oxidation even in the presence of adequate oxygen
      supply. Reductive analysis of each step of glycolysis shows that, of the three
      rate limiting enzymes of the pathway, isoforms of phosphofructokinase may afford
      the greatest opportunity as targets to deprive cancer cells from essential energy
      and substrates for macromolecular synthesis for proliferation while allowing
      normal cells to survive. Strategies discussed include restricting the substrate
      for this enzyme. While prospects for monotherapy with glycolytic inhibitors are
      poor, combination therapy may be productive. 

PMID- 24910090
TI  - Mass mortality associated with a viral-induced anaemia in cage-reared large
      yellow croaker, Larimichthys crocea (Richardson).

PMID- 24910091
TI  - Metabolomics of the rat lens: a combined LC-MS and NMR study.
AB  - This work is the first comprehensive report on the quantitative metabolomic
      composition of the rat lens. Quantitative metabolomic profiles of lenses were
      acquired with the combined use of high-frequency nuclear magnetic resonance (NMR)
      and high-performance liquid chromatography with high-resolution mass
      spectrometric detection (LC-MS) methods. More than forty low molecular weight
      compounds found in the lens have been reliably identified and quantified. The
      most abundant metabolites in the 3-month-old Wistar rat lens are taurine,
      hypotaurine, lactate, phosphocholine and reduced glutathione. The analysis of age
      related changes in the lens metabolomic composition shows a gradual decrease of
      the content of most metabolites. This decrease is the most pronounced between 1
      and 3 months, which probably corresponds to the completion of the lens maturation
      in one-month-old rats and to the high rate of the young lens growth. The enhanced
      levels of tryptophan, tyrosine, carnitine, glycerophosphate, GSH and GSSG were
      found in lenses of senescence-accelerated OXYS rats; for some metabolites, this
      effect may probably be attributed to the compensatory response to oxidative
      stress. 

PMID- 24910092
TI  - Evaluation of peritoneal CEA levels following colorectal cancer surgery.
AB  - BACKGROUND: Peritoneal carcinoembryonic antigen (pCEA) levels in the early
      postoperative period following a curative resection of colorectal cancer (CRC)
      have not been previously studied. METHODS: Postoperative peritoneal fluids of 36
      CRC patients followed by 24 benign colonic disease patients were evaluated for
      CEA levels and tumor cell presence. Serum CEA levels were also evaluated prior
      and after surgery. RESULTS: Although high postoperative pCEA levels were observed
      in some benign patients, more CRC patients exhibited significant elevation of
      postoperative pCEA (>5 ng/ml) compared to benign patients (50% vs. 23%, P =
      0.039). Postoperative median pCEA levels of CRC patients were significantly
      higher compared to benign patients (5.4 vs. 2 ng/ml, P = 0.011). Specifically,
      pCEA levels in CRC patients were significantly elevated when measured during the
      first 24 hr after surgery. Postoperative pCEA levels were associated with colon
      tumor location compared to rectal location. However, no correlation was found
      with known risk factors for cancer recurrence or with serum CEA levels.
      CONCLUSIONS: Postoperative pCEA levels may be significantly elevated following a
      curative resection for CRC. Its significance within patient's prognostic
      evaluation remains to be studied. Inclusion of patient's follow-up data may
      reveal the significance of elevated pCEA levels following CRC resection.

PMID- 24910094
TI  - Improving junior doctors' confidence in paediatric musculoskeletal assessment.
AB  - AIM: Musculoskeletal symptoms are a common cause for presentation of children and
      adolescents to health-care settings. Junior doctors report lack of confidence in
      assessment of the paediatric musculoskeletal system. Our aim was to assess the
      confidence of junior medical officers (JMOs) working in the emergency department
      (ED) with paediatric musculoskeletal assessment and determine if a readily
      available teaching module would improve confidence. METHODS: JMOs rostered to the
      paediatric ED were surveyed regarding their confidence in paediatric
      musculoskeletal assessment at the start and end of their ED rotation. A subgroup
      of these JMOs received formal teaching on paediatric musculoskeletal assessment
      using the paediatric gait, arm, leg and spine examination as part of their
      protected teaching time during their rotation. RESULTS: Forty-three JMOs were
      considered in the final analysis. Of those, 27 received teaching (intervention
      group), and 16 received no teaching (non-intervention group). In the intervention
      subgroup, there was a trend towards an increase in confidence in paediatric
      musculoskeletal assessment with the commonest response prior to the teaching
      intervention being 'some confidence' (11/27 41%) and the commonest response after
      teaching being 'fairly confident' (14/27 52%) without achieving statistical
      significance (P = 0.068). Of the JMOs in the intervention group, 26/27 (96%)
      found the teaching session useful, and 25/27 (93%) considered it relevant to
      their future practice. CONCLUSIONS: A clinical examination teaching intervention
      resulted in a trend towards an increase in confidence for JMOs in paediatric
      musculoskeletal assessment. Formal evaluation of a teaching module was feasible
      within the ED.

PMID- 24910095
TI  - NCOA4 transcriptional coactivator inhibits activation of DNA replication origins.
AB  - NCOA4 is a transcriptional coactivator of nuclear hormone receptors that
      undergoes gene rearrangement in human cancer. By combining studies in Xenopus
      laevis egg extracts and mouse embryonic fibroblasts (MEFs), we show here that
      NCOA4 is a minichromosome maintenance 7 (MCM7)-interacting protein that is able
      to control DNA replication. Depletion-reconstitution experiments in Xenopus
      laevis egg extracts indicate that NCOA4 acts as an inhibitor of DNA replication
      origin activation by regulating CMG (CDC45/MCM2-7/GINS) helicase. NCOA4(-/-) MEFs
      display unscheduled origin activation and reduced interorigin distance; this
      results in replication stress, as shown by the presence of fork stalling,
      reduction of fork speed, and premature senescence. Together, our findings
      indicate that NCOA4 acts as a regulator of DNA replication origins that helps
      prevent inappropriate DNA synthesis and replication stress. 

PMID- 24910096
TI  - Necessary and sufficient role for a mitosis skip in senescence induction.
AB  - Senescence is a state of permanent growth arrest and is a pivotal part of the
      antitumorigenic barrier in vivo. Although the tumor suppressor activities of p53
      and pRb family proteins are essential for the induction of senescence, molecular
      mechanisms by which these proteins induce senescence are still not clear. Using
      time-lapse live-cell imaging, we demonstrate here that normal human diploid
      fibroblasts (HDFs) exposed to various senescence-inducing stimuli undergo a
      mitosis skip before entry into permanent cell-cycle arrest. This mitosis skip is
      mediated by both p53-dependent premature activation of APC/C(Cdh1) and pRb family
      protein-dependent transcriptional suppression of mitotic regulators. Importantly,
      mitotic skipping is necessary and sufficient for senescence induction. p16 is
      only required for maintenance of senescence. Analysis of human nevi also
      suggested the role of mitosis skip in in vivo senescence. Our findings provide
      decisive evidence for the molecular basis underlying the induction and
      maintenance of cellular senescence.

PMID- 24910097
TI  - Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an
      ultraconserved region.
AB  - Noncoding RNAs (ncRNAs) control cellular programs by affecting protein-coding
      genes, but evidence increasingly points to their involvement in a network of
      ncRNA-ncRNA interactions. Here, we show that a long ncRNA, Uc.283+A, controls pri
      miRNA processing. Regulation requires complementarity between the lower stem
      region of the pri-miR-195 transcript and an ultraconserved sequence in Uc.283+A,
      which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA
      molecule uncouples regulation in vivo and in vitro. We propose a model in which
      lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and
      efficient pri-miRNA cropping. In addition to identifying a case of RNA-directed
      regulation of miRNA biogenesis, our study reveals regulatory networks involving
      different ncRNA classes of importance in cancer.

PMID- 24910098
TI  - Directed network wiring identifies a key protein interaction in embryonic stem
      cell differentiation.
AB  - Cell signaling depends on dynamic protein-protein interaction (PPI) networks,
      often assembled through modular domains each interacting with multiple peptide
      motifs. This complexity raises a conceptual challenge, namely to define whether a
      particular cellular response requires assembly of the complete PPI network of
      interest or can be driven by a specific interaction. To address this issue, we
      designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is
      highly biased toward a single phosphotyrosine (pY) motif among many potential
      pYXNX Grb2-binding sites. Surprisingly, directing Grb2 predominantly to a single
      pY site of the Ptpn11/Shp2 phosphatase, but not other sites tested, was
      sufficient for differentiation of the essential primitive endoderm lineage from
      embryonic stem cells. Our data suggest that discrete connections within complex
      PPI networks can underpin regulation of particular biological events. We propose
      that this directed wiring approach will be of general utility in functionally
      annotating specific PPIs.

PMID- 24910099
TI  - Transient activation of p53 in G2 phase is sufficient to induce senescence.
AB  - DNA damage can result in a transient cell-cycle arrest or lead to permanent cell
      cycle withdrawal. Here we show that the decision to irreversibly withdraw from
      the cell cycle is made within a few hours following damage in G2 cells. This
      permanent arrest is dependent on induction of p53 and p21, resulting in the
      nuclear retention of Cyclin B1. This rapid response is followed by the activation
      of the APC/C(Cdh1) (the anaphase-promoting complex/cyclosome and its coactivator
      Cdh1) several hours later. Inhibition of APC/C(Cdh1) activity fails to prevent
      cell-cycle withdrawal, whereas preventing nuclear retention of Cyclin B1 does
      allow cells to remain in cycle. Importantly, transient induction of p53 in G2
      cells is sufficient to induce senescence. Taken together, these results indicate
      that a rapid and transient pulse of p53 in G2 can drive nuclear retention of
      Cyclin B1 as the first irreversible step in the onset of senescence. 

PMID- 24910100
TI  - Identification of bacteriophage-encoded anti-sRNAs in pathogenic Escherichia
      coli.
AB  - In bacteria, Hfq is a core RNA chaperone that catalyzes the interaction of mRNAs
      with regulatory small RNAs (sRNAs). To determine in vivo RNA sequence
      requirements for Hfq interactions, and to study riboregulation in a bacterial
      pathogen, Hfq was UV crosslinked to RNAs in enterohemorrhagic Escherichia coli
      (EHEC). Hfq bound repeated trinucleotide motifs of A-R-N (A-A/G-any nucleotide)
      often associated with the Shine-Dalgarno translation initiation sequence in
      mRNAs. These motifs overlapped or were adjacent to the mRNA sequences bound by
      sRNAs. In consequence, sRNA-mRNA duplex formation will displace Hfq, promoting
      recycling. Fifty-five sRNAs were identified within bacteriophage-derived regions
      of the EHEC genome, including some of the most abundant Hfq-interacting sRNAs.
      One of these (AgvB) antagonized the function of the core genome regulatory sRNA,
      GcvB, by mimicking its mRNA substrate sequence. This bacteriophage-encoded "anti
      sRNA" provided EHEC with a growth advantage specifically in bovine rectal mucus
      recovered from its primary colonization site in cattle.

PMID- 24910102
TI  - Pilot dose-response trial of i.v. ketamine in treatment-resistant depression.
AB  - OBJECTIVES: Research studies have reported impressive antidepressant effects with
      ketamine but significant knowledge gaps remain over the best method of
      administering ketamine, and the relationships between dose, antidepressant
      response and adverse effects. METHODS: In this pilot dose-finding study, the
      efficacy and tolerability of ketamine given by rapid intravenous (i.v.) infusion
      were assessed in a double-blind, placebo-controlled, crossover design, in four
      subjects with treatment- resistant depression. Each subject received up to four
      i.v. doses of ketamine (0.1, 0.2, 0.3, 0.4 mg/kg), given over 2-5 min, 1 week
      apart, and one randomly inserted placebo treatment. RESULTS: Three of four
      subjects achieved antidepressant response (>= 50% decrease in Montgomery-Asberg
      Depression Rating Scale scores), two at the minimum 0.1 mg/kg dose, though all
      relapsed within a week. For two subjects, the greatest improvement occurred at
      the highest dose received. Rapid infusion over 2 min led to significant adverse
      psychotomimetic effects which also increased proportionately with ketamine
      dosage. CONCLUSIONS: This is the first trial to present dose-response data of
      ketamine efficacy and psychomimetic effects in depressed subjects. Antidepressant
      efficacy may be dose-related. Psychotomimetic effects were dose-related. Rapid
      infusion over 2 min may not be a feasible clinical approach to treatment, given
      poor tolerability.

PMID- 24910103
TI  - Impaired activation of the innate immune response to bacterial challenge in
      Tourette syndrome.
AB  - OBJECTIVES: Infections resulting in immune activation have been proposed to play
      an etiological role in a subgroup of patients with Tourette syndrome (TS).
      METHODS: In order to further characterize the interaction between pathogens and
      the innate immune system the toll-like receptor (TLR) 4 on CD14 + monocytes and
      soluble CD14 (sCD14) levels were analyzed in the serum of 33 Tourette patients
      and 31 healthy controls. Moreover, collected blood samples were stimulated with
      lipopolysaccharide (LPS) mimicking a bacterial infection. TLR4 was analysed by
      flow cytometry, sCD14 was analysed by enzyme-linked immunosorbent assay. RESULTS:
      Patients had a lower receptor expression of TLR4 after stimulation with LPS (P =
      0.045) and higher levels of sCD14 (unstimulated P = 0.014, after LPS P = 0.045).
      The increase in TLR4 expression after stimulation with LPS was significantly
      higher in the control group (P = 0.041). CONCLUSIONS: Higher levels of sCD14,
      lower levels of TLR4 expression after stimulation and a diminished up-regulation
      of TLR4 expression after LPS stimulation in patients might represent an impaired
      activation of the innate immune response in TS, especially in regard to bacterial
      infection. The impaired response to pathogens could eventually lead to a higher
      susceptibility for infections. Recurring infections and a chronic inflammation
      could trigger and maintain the symptoms of TS.

PMID- 24910101
TI  - A pair of RNA-binding proteins controls networks of splicing events contributing
      to specialization of neural cell types.
AB  - Alternative splicing is important for the development and function of the nervous
      system, but little is known about the differences in alternative splicing between
      distinct types of neurons. Furthermore, the factors that control cell-type
      specific splicing and the physiological roles of these alternative isoforms are
      unclear. By monitoring alternative splicing at single-cell resolution in
      Caenorhabditis elegans, we demonstrate that splicing patterns in different
      neurons are often distinct and highly regulated. We identify two conserved RNA
      binding proteins, UNC-75/CELF and EXC-7/Hu/ELAV, which regulate overlapping
      networks of splicing events in GABAergic and cholinergic neurons. We use the UNC
      75 exon network to discover regulators of synaptic transmission and to identify
      unique roles for isoforms of UNC-64/Syntaxin, a protein required for synaptic
      vesicle fusion. Our results indicate that combinatorial regulation of alternative
      splicing in distinct neurons provides a mechanism to specialize metazoan nervous
      systems. 

PMID- 24910104
TI  - Interactions between glia, the immune system and pain processes during early
      development.
AB  - Pain is a serious problem for infants and children and treatment options are
      limited. Moreover, infants born prematurely or hospitalized for illness likely
      have concurrent infection that activates the immune system. It is now recognized
      that the immune system in general and glia in particular influence
      neurotransmission and that the neural bases of pain are intimately connected to
      immune function. We know that injuries that induce pain activate immune function
      and suppressing the immune system alleviates pain. Despite this advance in our
      understanding, virtually nothing is known of the role that the immune system
      plays in pain processing in infants and children, even though pain is a serious
      clinical issue in pediatric medicine. This brief review summarizes the existing
      data on immune-neural interactions in infants, providing evidence for the
      immaturity of these interactions.

PMID- 24910105
TI  - Serum bilirubin concentrations are positively associated with serum C-peptide
      levels in patients with Type 2 diabetes.
AB  - AIMS: To investigate the relationship between physiological serum total bilirubin
      concentrations and serum C-peptide levels in Korean patients with Type 2
      diabetes. METHODS: A total of 588 patients with Type 2 diabetes were investigated
      in this cross-sectional study. Fasting C-peptide level, 2-h postprandial C
      peptide level and DeltaC-peptide (postprandial C-peptide minus fasting C-peptide)
      level were measured in all patients. RESULTS: Fasting C-peptide level,
      postprandial C-peptide level and DeltaC-peptide level tended to be higher in
      patients with higher bilirubin concentrations. Partial correlation analysis
      showed that serum bilirubin levels were significantly correlated with fasting C
      peptide level (r = 0.159, P < 0.001), postprandial C-peptide level (r = 0.209, P
      < 0.001) and DeltaC-peptide level (r = 0.186, P < 0.001) after adjustment for
      other covariates. In the multivariate model, the association between serum
      bilirubin concentrations and serum C-peptide levels remained significant after
      adjustment for confounding factors including age, gender, familial diabetes,
      hypertension, hyperlipidaemia, BMI, HbA1c , duration of diabetes and associated
      liver function tests (fasting C-peptide level: beta = 0.083, P = 0.041;
      postprandial C-peptide level: beta = 0.106, P = 0.005; DeltaC-peptide level: beta
      = 0.096, P = 0.015, respectively). CONCLUSIONS: Serum bilirubin concentrations
      within the physiological range were positively associated with serum C-peptide
      levels in patients with Type 2 diabetes.

PMID- 24910106
TI  - Diffusion of influenza viruses among migratory birds with a focus on the
      Southwest United States.
AB  - The Southwest United States, including Arizona and New Mexico, has a diverse
      climate and is home to many different avian species. We sequenced the
      hemagglutinin (HA) gene of twenty influenza specimens for the years 2007-2009.
      This included four from Arizona, and sixteen from New Mexico. We analyzed the
      sequences and determined the following HA subtypes: H3, H4, H6, H8, and H11. For
      each subtype, we combined our virus sequences with those from a public database,
      and inferred phylogeographic models of influenza diffusion. Statistical
      phylogeography indicated that overall evolutionary diffusion of avian influenza
      viruses is geographically structured (p<0.05). In addition, we found that
      diffusion to the Southwest was often from nearby states including California. For
      H3, H4 and H6, the intra-flyway gene flow rates were significantly (p<0.001)
      higher than those of inter-flyway. Such rate difference was also observed in H8
      and H11, yet, without statistical significance (p=0.132, p=0.190, respectively).
      Excluding any one flyway from the calculation generated similar results,
      suggesting that such barrier effect on gene flow rates is not exclusively
      produced by any single flyway. We also calculated the Bayes factor test for the
      significant non-zero rates between states and identified significant routes both
      within and across flyways. Such inter-flyway spread of influenza was probably the
      result of birds from four flyways co-mingling on breeding grounds in northern
      regions or marshaling on staging areas post breeding in Canada or Alaska, before
      moving south each fall. This study provides an initial analysis of evolutionary
      diffusion of avian influenza virus to and from the Southwest United States.
      However, more sequences from this region need to be generated to determine the
      role of host migration and other factors on influenza diffusion. 

PMID- 24910107
TI  - Naturally occurring Toll-like receptor 11 (TLR11) and Toll-like receptor 12
      (TLR12) polymorphisms are not associated with Toxoplasma gondii infection in wild
      wood mice.
AB  - Toxoplasma gondii is a highly successful parasite with a worldwide prevalence.
      Small rodents are the main intermediate hosts, and there is growing evidence that
      T. gondii modifies their behaviour. Chronically infected rodents show impaired
      learning capacity, enhanced activity, and, most importantly, a reduction of the
      innate fear towards cat odour. This modification of host behaviour ensures a
      successful transmission of T. gondii from rodents to felids, the definitive hosts
      of the parasite. Given the negative fitness consequences of this behavioural
      manipulation, as well as an increased mortality during the acute phase of
      infection, we expect rodents to evolve potent resistance mechanisms that prevent
      or control infection. Indeed, studies in laboratory mice have identified
      candidate genes for T. gondii resistance. Of particular importance appear to be
      the innate immune receptors Toll-like receptor 11 (TLR11) and Toll-like receptor
      12 (TLR12), which recognise T. gondii profilin and initiate immune responses
      against the parasite. Here we analyse the genetic diversity of TLR11 and TLR12 in
      a natural population of wood mice (Apodemus sylvaticus), and test for
      associations between TLR11 and TLR12 polymorphisms and T. gondii infection, as
      well as for epistatic interactions between TLR11 and TLR12 on infection status.
      We found that both TLR11 and TLR12 were polymorphic in wood mice, with four and
      nine amino acid haplotypes, respectively. However, we found no evidence that
      TLR11 or TLR12 genotypes or haplotypes were significantly associated with
      Toxoplasma infection. Despite the importance of TLR11 and TLR12 in T. gondii
      recognition and immune defence initiation, naturally occurring polymorphisms at
      TLR11 and TLR12 thus appear to play a minor role in mediating qualitative
      resistance to T. gondii in natural host populations of A. sylvaticus. This
      highlights the importance of assessing the role of candidate genes for parasite
      resistance identified in a laboratory setting in an ecologically meaningful
      context to quantify their role in mediating host-parasite interactions in the
      wild. 

PMID- 24910108
TI  - Interunit handoffs of patients and transfers of information: a survey of current
      practices.
AB  - STUDY OBJECTIVE: We describe the current state of emergency department to
      inpatient handoffs and assess handoff best practices between emergency physicians
      and hospitalist medicine physicians. METHODS: A survey was distributed
      electronically to emergency medicine and internal medicine physicians at 10
      hospitals across the United States. Descriptive and quantitative analysis was
      performed on survey results. Additionally, qualitative data were obtained from an
      expert focus group of both emergency medicine and hospital medicine clinicians.
      RESULTS: Seven hundred fifty of 1,799 physicians (42.2%) responded to our Web
      based survey. Attending physicians (45%) described themselves as practicing
      emergency medicine (51%) or internal medicine (56%). Responding residents were
      55% internal medicine, 43% emergency medicine, and 13% dual emergency
      medicine/internal medicine. Of the responding departments, use of standardized
      tools was reported by less than 20% and only one third of residents reported
      formal handoff training. Handoff factors identified as important include
      identifying "high-risk" patients, designating uninterrupted time to perform the
      handoff, and standardizing information provided during the handoff. Qualitative
      results mirrored these themes and acknowledged the importance of bedside
      handoffs. CONCLUSION: To our knowledge, this is the largest multispecialty survey
      to date, including both resident and attending physicians in emergency medicine
      and hospital medicine. Standardized tools are rarely used and training of
      residents in this critical task is uncommon. Physicians in both specialties agree
      on the important content and structure of handoff, including the ideal situation
      of face-to-face bedside discussion. A curriculum and assessment tool for this
      practice should be developed.

PMID- 24910109
TI  - Prevalence and associated factors of obstructive sleep apnea in hospitalized
      patients with type 2 diabetes in Beijing, China 2.
AB  - BACKGROUND: The aim of the present study was to assess the prevalence and risk
      factors associated with obstructive sleep apnea (OSA) in hospitalized patients
      with type 2 diabetes mellitus (T2DM) in China. METHODS: Patients with T2DM who
      were hospitalized in four facilities in Beijing were invited to participate in
      the study. In all, 337 patients were enrolled consecutively, and 210 (62.3%)
      completed the study. Data from 472 patients in a non-consecutive expanding study
      were analyzed for the association study. A portable monitoring device was used to
      detect the presence of OSA. The apnea-hypopnea index (AHI) and the lowest level
      of oxygen saturation during the night were recorded to evaluate the severity of
      OSA. Logistic regression analysis was used to estimate the odds ratio (OR) for
      OSA for risk factors. RESULTS: The prevalence of OSA was 66.7%. The prevalence of
      moderate to severe OSA (AHI >=15/h) was 20.0%. The multi-adjusted OR (95%
      confidence interval) estimating OSA corresponding to a 1-year increase in age was
      1.06 (1.04, 1.08), whereas that to a 1-kg/m(2) increase in body mass index (BMI)
      was 1.18 (1.11, 1.26). The lowest oxygen saturation was associated with
      proliferative diabetic retinopathy (PDR) and cerebral infarction; the
      multivariate adjusted OR (95% CI) corresponding to a 1% increase in lowest oxygen
      saturation were 0.95 (0.92, 0.99) and 0.97 (0.94, 0.99), respectively.
      CONCLUSION: A high prevalence of OSA was observed in this sample of patients with
      T2DM in China. Age and BMI were associated with the presence of OSA. The lowest
      oxygen saturation was independently associated with the presence of PDR and
      cerebral infarction.

PMID- 24910110
TI  - Solvation chemistry of water-soluble thiol-protected gold nanocluster Au102 from
      DOSY NMR spectroscopy and DFT calculations.
AB  - The hydrodynamic diameter of Aum(pMBA)n [(m, n) = (102, 44) and (144, 60)]
      clusters in aqueous media was determined via DOSY NMR spectroscopy. The apparent
      size of the same (n, m) cluster depends on the counter ion of the deprotonated
      pMBA(-) ligand as explained by the competing ion-pair strength and hydrogen
      bonding interactions studied in DFT calculations. The choice of the counter ion
      affects the surface chemistry and molecular structure at the organic/water
      interface, which is relevant for biological applications. 

PMID- 24910112
TI  - Cyclic azacyanines: experimental and computational studies on spectroscopic
      properties and unique reactivity.
AB  - The absorption and fluorescence properties of cyclic azacyanine (CAC) derivatives
      were examined in several solvents. The presence of electron donating or
      withdrawing groups on the CAC impacts spectroscopic properties. The general
      solvent relaxation displayed by azacyanine derivatives is in accordance with
      Lippert-Mataga's prediction but exception is noted in the case of protic solvent
      due to specific hydrogen bonding interactions. Fluorescence lifetime decay
      studies indicate a relaxation time in the nanosecond timescale with mono
      exponential decay. Donating substituents markedly increase the excited state
      lifetime, whereas withdrawing groups marginally decrease the excited state
      lifetime. Quantum chemical computations were used to explore the origins of the
      reactivity and spectroscopic properties of CACs; results are consistent with a
      model in which regioselectivity results from differences in mechanistic steps
      occurring after initial attack by hydroxide on the CAC. 

PMID- 24910111
TI  - Determination of kinetics and the crystal structure of a novel type 2 isopentenyl
      diphosphate: dimethylallyl diphosphate isomerase from Streptococcus pneumoniae.
AB  - Isopentenyl diphosphate isomerase (IDI) is a key enzyme in the isoprenoid
      biosynthetic pathway and is required for all organisms that synthesize isoprenoid
      metabolites from mevalonate. Type 1 IDI (IDI-1) is a metalloprotein that is found
      in eukaryotes, whereas the type 2 isoform (IDI-2) is a flavoenzyme found in
      bacteria that is completely absent from human. IDI-2 from the pathogenic
      bacterium Streptococcus pneumoniae was recombinantly expressed in Escherichia
      coli. Steady-state kinetic studies of the enzyme indicated that FMNH2 (KM =0.3
      MUM) bound before isopentenyl diphosphate (KM =40 MUM) in an ordered binding
      mechanism. An X-ray crystal structure at 1.4 A resolution was obtained for the
      holoenzyme in the closed conformation with a reduced flavin cofactor and two
      sulfate ions in the active site. These results helped to further approach the
      enzymatic mechanism of IDI-2 and, thus, open new possibilities for the rational
      design of antibacterial compounds against sequence-similar and structure-related
      pathogens such as Enterococcus faecalis or Staphylococcus aureus. 

PMID- 24910113
TI  - Size-dependent electrochemical magnesium storage performance of spinel lithium
      titanate.
AB  - Li4 Ti5 O12 nanoparticles (LTO NPs) with different particle sizes were
      synthesized by a simple sol-gel progress. The effect of LTO particle size on the
      electrochemical behavior in Mg secondary batteries was investigated. Results
      showed that magnesium storage behaviors in LTO are strongly size dependent. The
      Mg(2+) electrochemical insertion into LTO becomes notable only when the particle
      size is below 40 nm. Moreover, the theoretical maximum capacity of LTO can be
      reached in crystallite sizes less than 10 nm. LTO NPs with 7-8 nm in size
      exhibited a substantial reversible capacity of 175 mA h g(-1) and outstanding
      cycling stability, maintaining 95 % capacity retention after 500 cycles. This
      result indicates that the LTO NPs with average particle size of 7-8 nm have high
      potential for use in high-rate and durable Mg secondary batteries. These results
      provide insight into how confining particles to nanosize will be critical to the
      preparation of suitable electrode materials for Mg secondary batteries. 

PMID- 24910114
TI  - Aortic thrombosis secondary to clopidogrel-related thrombotic thrombocytopenic
      purpura.

PMID- 24910115
TI  - Gold-catalyzed C(sp3)-H/C(sp)H coupling/cyclization/oxidative alkynylation
      sequence: a powerful strategy for the synthesis of 3-alkynyl polysubstituted
      furans.
AB  - In sharp contrast to the gold-catalyzed reactions of alkynes/allenes with
      nucleophiles, gold-catalyzed oxidative cross-couplings and especially C-H/C-H
      cross-coupling have been under represented. By taking advantage of the unique
      redox property and carbophilic pi acidity of gold, this work realizes the first
      gold-catalyzed direct C(sp(3))-H alkynylation of 1,3-dicarbonyl compounds with
      terminal alkynes under mild reaction conditions, with subsequent cyclization and
      in situ oxidative alkynylation. A variety of terminal alkynes including aryl,
      heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully
      participate in the domino reaction. The protocol offers a simple and region
      defined approach to 3-alkynyl polysubstituted furans.

PMID- 24910116
TI  - Comparative transcriptomic analysis by RNA-seq to discern differential expression
      of genes in liver and muscle tissues of adult Berkshire and Jeju Native Pig.
AB  - RNA-seq is being rapidly adopted for the profiling of the transcriptomes in
      different areas of biology, especially in the studies related to gene regulation.
      The discovery of differentially expressed genes (DEGs) between adult animals of
      Jeju Native Pig (JNP) and Berkshire breeds of Sus scrofa, is of particular
      interest for the current study. For the better understanding of the gene
      expression profiles of the liver and longissimus dorsi muscle, DEGs were
      identified via RNA-seq. Sequence reads were obtained from Illumina HiSeq2000 and
      mapped to the pig reference genome (Sscrofa10.2) using Tophat2. We identified 169
      and 39 DEGs in the liver and muscle of JNP respectively, by comparison with
      Berkshire breed. Out of all identified genes, 41 genes in the liver and 9 genes
      in the muscle have given significant expression. Gene ontology (GO) terms of
      developmental process and KEGG pathway analysis showed that metabolic, immune
      response and protein binding were commonly enriched pathways in the two tissues.
      Further the heat map analysis by ArrayStar has shown the different levels of
      expression in JNP with respect to the Berkshire breed. The validation through
      real time PCR and western blotting also confirmed the differential expression of
      genes in both breeds. Genes pertaining to metabolic process and inflammatory and
      immune system are more enriched in Berkshire breed. This comparative
      transcriptome analysis of two tissues suggests a subset of novel marker genes
      which expressed differently between the JNP and Berkshire. 

PMID- 24910117
TI  - Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of
      PI3K/Akt signaling pathway.
AB  - The objectives of this study were to evaluate the in vitro anti-tumor (human
      thyroid cancer cell lines) potential of curcumin and to elucidate its molecular
      mechanisms. Here, we investigated the effects of curcumin on the cell viability,
      apoptosis, migration and invasion of human thyroid cancer cell lines FTC133. We
      also investigated the effects of curcumin on PI3K, p-Akt, MMP1/7, and COX-2
      protein expressions using Western blot. Results showed that curcumin inhibited
      growth, cell migration and invasion in FTC133, and promoted its apoptosis.
      Western blot assay data demonstrated that curcumin inhibited phosphorylation of
      PI3K and Akt signaling pathways and subsequently attenuated MMP1/7 and COX-2
      protein expressions in FTC133. In conclusion, curcumin suppresses FTC133 cell
      invasion and migration by inhibiting PI3K and Akt signaling pathways. Therefore,
      curcumin produces anti-metastatic activity in FTC133 cells. 

PMID- 24910118
TI  - The safety and tolerability of intranasal midazolam in epilepsy.
AB  - Midazolam is a short-acting benzodiazepine that has clearly demonstrated to be an
      effective option for the acute management of epileptic seizures. It has the
      advantage of being water-soluble, with a rapid onset of action and it can be
      administered orally or intranasally, implementing an early intervention at the
      pre-hospital setting. This article aims to provide an overview of intranasal
      midazolam in the acute management of epileptic seizures. Available data suggest
      that midazolam 0.2 mg/kg is as effective as diazepam 0.5 mg/kg, especially in
      children with febrile or afebrile seizures. Local mucosal irritation seems to
      occur in less than one-third of cases while serious side effects such as
      respiratory depression in about 1%. Future studies need to be focused on adults
      and optimized technologies for intranasal delivery. Moreover, comparisons with
      buccal midazolam are warranted. 

PMID- 24910121
TI  - Journal of Viral Hepatitis commencing January 2015.

PMID- 24910122
TI  - High seroprevalence of hepatitis B virus and hepatitis C virus among human
      immunodeficiency virus carriers in blood donors of Burkina Faso: a need for their
      screening before HARRT therapy.

PMID- 24910120
TI  - Identification of novel functional regions within the spike glycoprotein of MHV
      A59 based on a bioinformatics approach.
AB  - Mouse Hepatitis Virus (MHV) is a single-stranded positive sense RNA virus with
      the ability to promote acute and chronic diseases in mice. The MHV spike protein
      (S) is a major virulence determinant which in addition to binding to cellular
      receptors to mediate cell entry and facilitate virus spread to adjacent cells by
      cell-cell fusion, also is a molecular mimic of the FcgammaRII receptor. This
      molecular mimicry of FcgammaRII by the MHV S protein is also exhibited by other
      lineage 2a betacoronaviruses, with the exception of the human coronavirus HCoV
      OC43. In this work we undertook a mutational analysis to attempt to identify
      specific amino acid sequences within the spike glycoprotein crucial for molecular
      mimicry of FcgammaRII. Although we were unsuccessful in isolating mutant viruses
      which were specifically defective in that property, we identified several
      mutations with interesting phenotypes. Mutation of the cysteine in position 547
      to alanine and alanine replacements at residues 581-586 was lethal. Replacing
      proline 939 with the corresponding HCoV-OC43 residue, leucine, decreased the
      ability MHV to induce cell-cell fusion, providing experimental support for an
      earlier proposal that residues 929-944 make up the fusion peptide of the MHV S
      protein. 

PMID- 24910119
TI  - Aberrant sumoylation signaling evoked by reactive oxygen species impairs
      protective function of Prdx6 by destabilization and repression of its
      transcription.
AB  - Loss of the cytoprotective protein peroxiredoxin 6 (Prdx6) in cells that are
      aging or under oxidative stress is known to be linked to the pathobiology of many
      age-related diseases. However, the mechanism by which Prdx6 activity goes awry is
      largely unknown. Using Prdx6-deficient (Prdx6(-/-) ) cells as a model for aging
      or redox active cells, human/mouse lens epithelial cells (LECs) facing oxidative
      stress and aging lenses, we found a significant increase in the levels of small
      ubiquitin-like modifier (Sumo)1 conjugates. These cells displayed increased
      levels of Sumo1 and reduced the expression of Prdx6. Specifically, we observed
      that Prdx6 is a target for aberrant sumoylation signaling, and that Sumo1
      modification reduces its cellular abundance. LECs overexpressing Sumo1 showed
      reduced expression and activity of Prdx6 and its transactivator specificity
      protein 1 (Sp1), mRNA and protein with increased levels of reactive oxygen
      species; those cells were vulnerable to oxidative stress-induced cell death. A
      significant reduction in Prdx6, Sp1 protein and mRNA expression was observed in
      redox active Prdx6(-/-) cells and in aging lenses/LECs. The reduction was
      correlated with increased expression of Sumo1 and enrichment of the inactive form
      (dimeric) of Sumo-specific protease (Senp)1. Experiments with Sumo1-fused Prdx6
      and Prdx6 promoter-linked to chloramphenicol acetyltransferase reporter gene
      constructs indicated that Sumo1 dysregulated Prdx6 activity by reducing its
      abundance and attenuating its transcription; in contrast, the delivery of Senp1
      or Prdx6 reversed the process. The data show that reactive oxygen species-evoked
      aberrant sumoylation signaling affects Prdx6 activity by reducing Prdx6
      abundance, as well as transcription. The findings of the present study may
      provide a foundation for a strategy to repair deleterious oxidative signaling
      generated by a reduced activity of Prdx6. 

PMID- 24910123
TI  - Modified spleen stiffness measurement: a step forward, but still not the solution
      to all problems in the noninvasive assessment of cirrhotic patients.

PMID- 24910124
TI  - Short-term spontaneous regression of myxofibrosarcoma in the scapular region.
AB  - Spontaneous regression of cancer is a well-known but rare phenomenon, and it is
      extremely rare for sarcomas. The current case is an 85-year-old woman with a
      multinodular lesion diagnosed as myxofibrosarcoma in the scapular region. The
      maximum size of the tumor at the initial visit was 10 cm, and it decreased to
      less than 2 cm without any treatment. After a period of regression of about 6
      months, the tumor began to grow, and resection was performed. No prior case of
      spontaneous regression has been reported in myxofibrosarcoma or other primary
      sarcomas. Interestingly, the regression took place after the occurrence of
      pneumonia, suggesting a possible relationship. 

PMID- 24910126
TI  - Lateral midfoot pain.

PMID- 24910125
TI  - Total hip prosthesis CT with single-energy projection-based metallic artifact
      reduction: impact on the visualization of specific periprosthetic soft tissue
      structures.
AB  - OBJECTIVES: To compare the image quality of CT with iterative reconstruction
      alone and in association with projection-based single-energy metal artifact
      reduction (SEMAR) for the visualization of specific periarticular soft tissue
      structures in patients with hip prostheses. METHODS: CT studies from 48
      consecutive patients with a hip prosthesis (24 unilateral and 24 bilateral) were
      retrospectively reconstructed using two different methods: iterative
      reconstruction (IR) alone and IR associated with SEMAR. The influence of metallic
      artifacts on the identification of various periarticular structures was evaluated
      subjectively by two readers. The image quality was compared in patients with
      unilateral and bilateral prostheses. RESULTS: Visualization of periprosthetic
      soft tissue was significantly improved by the SEMAR algorithm (p < 0.0001). When
      SEMAR was associated with IR, the gluteus minimus and medius tendons, obturator
      internus muscle, prostate/uterus and bladder could be seen with medium or high
      confidence. There were no significant differences in image quality between
      patients with unilateral or bilateral prosthesis when SEMAR was used (p > 0.2).
      This algorithm increased the detection of periarticular masses by 30%.
      CONCLUSION: SEMAR significantly improves the image quality of periarticular soft
      tissue structures in patients with hip prostheses.

PMID- 24910127
TI  - Raman spectroscopic study of structural changes upon chilling storage of
      frankfurters containing olive oil bulking agents as fat replacers.
AB  - Technological properties and structural characteristics of proteins and lipids,
      using Raman spectroscopy, of frankfurters formulated with olive oil bulking
      agents as animal fat replacers were examined during chilling storage.
      Frankfurters reformulated with oil bulking agents showed lower (P<0.05)
      processing loss and higher (P<0.05) hardness and chewiness. Purge loss during
      chilling storage was relatively low, demonstrating a good water retention in the
      products. beta-Sheet structures were enhanced by the use of olive oil bulking
      agents, and this effect was more pronounced in samples containing inulin.
      Reformulated frankfurters contained the least turns (P<0.05). A significant
      decrease of beta-sheets and an increase of turns were observed after 85 days of
      chilled storage. The lowest (P<0.05) values of InusCH2/InuasCH2 were recorded in
      frankfurters reformulated with oil bulking agents, which suggests more lipid acyl
      chain disorder. Structural characteristics were correlated to processing losses,
      hardness, and chewiness.

PMID- 24910130
TI  - The anion-binding polyanion: a molecular cobalt vanadium oxide with anion
      sensitive visual response.
AB  - An anionic molecular cobalt vanadium oxide cluster, (n-Bu4N)3[Co(AcO)V4O12] and
      its use as anion binding site is reported. Cluster formation is controlled by an
      anion-dependent dynamic solution equilibrium. Reversible anion binding in
      solution leads to significant spectral changes, allowing the ratiometric optical
      detection of the anion concentration in situ, even under harsh thermal conditions
      (T = 90  degrees C). Comparative studies showed that the spectral response is
      dependent on the type of anion so that carboxylates, weakly coordinating anions
      and halides can be distinguished. 

PMID- 24910129
TI  - Human B cells induce dendritic cell maturation and favour Th2 polarization by
      inducing OX-40 ligand.
AB  - Dendritic cells (DCs) play a critical role in immune homeostasis by regulating
      the functions of various immune cells, including T and B cells. Notably, DCs also
      undergo education on reciprocal signalling by these immune cells and
      environmental factors. Various reports demonstrated that B cells have profound
      regulatory functions, although only few reports have explored the regulation of
      human DCs by B cells. Here we demonstrate that activated but not resting B cells
      induce maturation of DCs with distinct features to polarize Th2 cells that
      secrete interleukin (IL)-5, IL-4 and IL-13. B-cell-induced maturation of DCs is
      contact dependent and implicates signalling of B-cell activation molecules CD69,
      B-cell-activating factor receptor, and transmembrane activator and calcium
      modulating cyclophilin ligand interactor. Mechanistically, differentiation of Th2
      cells by B-cell-matured DCs is dependent on OX-40 ligand. Collectively, our
      results suggest that B cells have the ability to control their own effector
      functions by enhancing the ability of human DCs to mediate Th2 differentiation. 

PMID- 24910128
TI  - An RNA polymerase II-coupled function for histone H3K36 methylation in checkpoint
      activation and DSB repair.
AB  - Histone modifications are major determinants of DNA double-strand break (DSB)
      response and repair. Here we elucidate a DSB repair function for transcription
      coupled Set2 methylation at H3 lysine 36 (H3K36me). Cells devoid of Set2/H3K36me
      are hypersensitive to DNA-damaging agents and site-specific DSBs, fail to
      properly activate the DNA-damage checkpoint, and show genetic interactions with
      DSB-sensing and repair machinery. Set2/H3K36me3 is enriched at DSBs, and loss of
      Set2 results in altered chromatin architecture and inappropriate resection during
      G1 near break sites. Surprisingly, Set2 and RNA polymerase II are programmed for
      destruction after DSBs in a temporal manner--resulting in H3K36me3 to H3K36me2
      transition that may be linked to DSB repair. Finally, we show a requirement of
      Set2 in DSB repair in transcription units--thus underscoring the importance of
      transcription-dependent H3K36me in DSB repair.

PMID- 24910131
TI  - Associations of cigarette smoking and alcohol consumption with metabolic syndrome
      in a male Chinese population: a cross-sectional study.
AB  - BACKGROUND: Whether cigarette smoking and alcohol consumption are associated with
      the risk of metabolic syndrome (MetS) remains controversial. This study
      investigated the associations of cigarette smoking and alcohol consumption with
      MetS in a male population in China. METHODS: We conducted a cross-sectional
      study. A questionnaire was used to collect data on cigarette smoking, alcohol
      consumption, MetS status, and other related information from 8169 men aged 19-97
      years. Logistic regression was used to estimate the odds ratios (ORs) and 95%
      confidence intervals (CIs) for the associations between smoking and alcohol
      consumption and the risk of MetS. RESULTS: The prevalence of MetS was 15.2% in
      the study population. Proportions of current smokers and drinkers were 48.2% and
      46.5%, respectively. Adjusted OR of MetS was 1.34 (95% CI, 1.01-1.79) among
      smokers who smoked >=40 cigarettes/day compared with nonsmokers and 1.22 (95% CI
      1.03-1.46) for those who consumed 0.1-99 grams of alcohol/day compared with
      nondrinkers. Adjusted OR was 2.32 (95% CI 1.45-3.73) among ex-drinkers who never
      smoked, 1.98 (95% CI 1.35-2.91) among ex-drinkers who were current smokers, and
      1.34 (95% CI 1.08-1.68) among current drinkers who never smoked compared with
      those who neither smoked nor drank. There was a significant interaction between
      smoking and drinking alcohol on MetS (P for interaction is 0.001). CONCLUSIONS:
      Our study indicated that smoking and drinking is associated with higher
      prevalence of MetS. Interactions between smoking and drinking on the risk of MetS
      in men in China may also exist. Our findings need to be confirmed in future case
      control or cohort studies.

PMID- 24910133
TI  - Face of a fighter: Bizygomatic width as a cue of formidability.
AB  - Humans can accurately extract information about men's formidability from their
      faces; however, the actual facial cues that inform these judgments have not been
      established. Here, through three studies, we test the hypothesis that bizygomatic
      width (i.e. facial width-to-height ratio, fWHR) covaries with actual physical
      formidability (hypothesis #1) and that humans use this cue when making
      assessments of formidability (hypothesis #2). Our data confirm that fWHR is
      predictive of actual fighting ability among professional combatants (study 1). We
      further show that subjects' assessments of formidability covary with the target's
      fWHR on natural faces (study 2), computer-generated images of strong and weak
      faces (study 2), and experimentally manipulated computer-generated faces (study
      3). These results support the hypothesis that bizygomatic width is a cue of
      formidability that is assessed during agonistic encounters.

PMID- 24910132
TI  - Osteophytes, enthesophytes, and high bone mass: a bone-forming triad with
      potential relevance in osteoarthritis.
AB  - OBJECTIVE: Previous studies of skeletal remains have suggested that both
      enthesophytes and osteophytes are manifestations of an underlying bone-forming
      tendency. A greater prevalence of osteophytes has been observed among individuals
      with high bone mass (HBM) compared with controls. This study was undertaken to
      examine the possible interrelationships between bone mass, enthesophytes, and
      osteophytes in a population of individuals with extreme HBM. METHODS: Cases of
      HBM (defined according to bone mineral density [BMD] Z scores on dual x-ray
      absorptiometry) from the UK-based HBM study were compared with a control group
      comprising unaffected family members and general population controls from the
      Chingford and Hertfordshire cohort studies. Pelvic radiographs from cases and
      controls were pooled and evaluated, in a blinded manner, by a single observer,
      who performed semiquantitative grading of the radiographs for the presence and
      severity of osteophytes and enthesophytes (score range 0-3 for each). Logistic
      regression analysis was used to identify significant associations, with a priori
      adjustment for age, sex, and body mass index. RESULTS: In this study, 226
      radiographs from HBM cases and 437 radiographs from control subjects were
      included. Enthesophytes (grade >=1) and moderate enthesophytes (grade >=2) were
      more prevalent in HBM cases compared with controls (adjusted odds ratio [OR] 3.00
      [95% confidence interval (95% CI) 1.96-4.58], P < 0.001 for any enthesophyte;
      adjusted OR 4.33 [95% CI 2.67-7.02], P < 0.001 for moderate enthesophytes). In
      the combined population of cases and controls, the enthesophyte grade was
      positively associated with BMD at both the total hip and lumbar spine (adjusted P
      for trend < 0.001). In addition, a positive association between osteophytes and
      enthesophytes was observed; for each unit increase in enthesophyte grade, the
      odds of any osteophyte being present were increased >2-fold (P < 0.001).
      CONCLUSION: Strong interrelationships were observed between osteophytes,
      enthesophytes, and HBM, which may be helpful in defining a distinct subset of
      patients with osteoarthritis characterized by excess bone formation.

PMID- 24910134
TI  - Study on the use of 3-aminopropyltriethoxysilane and 3
      chloropropyltriethoxysilane to surface biochemical modification of a novel low
      elastic modulus Ti-Nb-Hf alloy.
AB  - A biocompatible new titanium alloy Ti-16Hf-25Nb with low elastic modulus (45 GPa)
      and the use of short bioadhesive peptides derived from the extracellular matrix
      have been studied. In terms of cell adhesion, a comparative study with mixtures
      of short peptides as RGD (Arg-Gly-Asp)/PHSRN (Pro-His-Ser-Arg-Asn) and RGD (Arg
      Gly-Asp)/FHRRIKA (Phe-His-Arg-Arg-Ile-Lys-Ala) have been carried out with rat
      mesenchymal cells. The effect of these mixtures of short peptides have already
      been studied but there are no comparative studies between them. Despite the wide
      variety of silane precursors available for surface modification in pure titanium,
      the majority of studies have used aminosilanes, in particular 3
      minopropyltriethoxysilane (APTES). Nevertheless, the 3
      chloropropyltriethoxysilane (CPTES) is, recently, proposed by other authors.
      Unlike APTES, CPTES does not require an activation step and offers the potential
      to directly bind the nucleophilic groups present on the biomolecule (e.g., amines
      or thiols). Since the chemical surface composition of this new alloy could be
      different to that pure titanium, both organosilanes have been compared and
      characterized by means of a complete surface characterization using contact angle
      goniometry and X-ray photoelectron spectroscopy.

PMID- 24910135
TI  - A mechanistic in vitro study of the microgalvanic degradation of secondary phase
      particles in magnesium alloys.
AB  - The aim of this work was to understand the effect of microgalvanic degradation on
      secondary phase particles in magnesium alloys under in vitro condition. Pure
      magnesium and Mg17 Al12 (beta-phase) were galvanically coupled in simulated body
      fluid and the degradation behavior was studied using electrochemical impedance
      spectroscopy. The galvanic coupling produced a phosphate/carbonate layer on the
      beta-phase, which initially increased the degradation resistance. However, the
      deposited phosphate/carbonate layer rapidly degraded once the galvanic coupling
      was removed, and beta-phase exhibited similar degradation resistance to that of
      pure magnesium. A phenomenological model has been presented, demonstrating the
      galvanic coupling effect.

PMID- 24910136
TI  - Red Junglefowl (Gallus gallus) selected for low fear of humans are larger, more
      dominant and produce larger offspring.
AB  - Many traits associated with domestication are suggested to have developed as
      correlated responses to reduced fear of humans. Tameness may have reduced the
      stress of living in human proximity and improved welfare in captivity. We
      selected Red Junglefowl (ancestors of all domestic chickens) for four generations
      on high or low fear towards humans, mimicking an important aspect of the earliest
      period of domestication, and tested birds from the third and fourth generation in
      three different social tests. Growth and plumage condition, as well as size of
      eggs and offspring were also recorded, as indicators of some aspects of welfare.
      Birds selected for low fear had higher weight, laid larger eggs and generated
      larger offspring, and had a better plumage condition. In a social dominance test
      they also performed more aggressive behaviour and received less of the same,
      regardless of whether the restricted resource was feed or not. Hence, dominance
      appeared to increase as a consequence of reduced fear of humans. Furthermore, egg
      size and the weight of the offspring were larger in the less fearful birds, and
      plumage condition better, which could be interpreted as the less fearful animals
      being better adapted to the environment in which they were selected. 

PMID- 24910137
TI  - ANI inactivation: unconditioned anxiolytic effects of anisomycin in the ventral
      hippocampus.
AB  - Although hippocampal function is typically described in terms of memory, recent
      evidence suggests a differentiation along its dorsal/ventral axis, with dorsal
      regions serving memory and ventral regions serving emotion. While long-term
      memory is thought to be dependent on de novo protein synthesis because it is
      blocked by translational inhibitors such as anisomycin (ANI), online (moment-to
      moment) functions of the hippocampus (such as unconditioned emotional responding)
      should not be sensitive to such manipulations since they are unlikely to involve
      neuroplasticity. However, ANI has recently been shown to suppress neural activity
      which suggests (1) that protein synthesis is critical for neural function and (2)
      that paradigms using ANI are confounded by its inactivating effects. We tested
      this idea using a neurobehavioral assay which compared the influence of
      intrahippocampal infusions of ANI at dorsal and ventral sites on unconditioned
      emotional behavior of rats. We show that ANI infusions in ventral, but not
      dorsal, hippocampus produced a suppression of anxiety-related responses in two
      well-established rodent tests: the elevated plus maze and shock-probe burying
      tests. These results are similar to those previously observed when ventral
      hippocampal activity is directly suppressed (e.g., by using sodium channel
      blockers). The present study offers compelling behavioral evidence for the
      proposal that ANI adversely affects ongoing neural function and therefore its
      influence is not simply limited to impairing the consolidation of long-term
      memories

PMID- 24910138
TI  - Tests of unconditioned anxiety - pitfalls and disappointments.
AB  - The plus-maze, the light-dark box and the open-field are the main current tests
      of unconditioned anxiety for mice and rats. Despite their disappointing
      achievements, they remain as popular as ever and seem to play an important role
      in an ever-growing demand for behavioral phenotyping and drug screening. Numerous
      reviews have repeatedly reported their lack of consistency and reliability but
      they failed to address the core question of whether these tests do provide
      unequivocal measures of fear-induced anxiety, that these measurements are not
      confused with measures of fear-induced avoidance or natural preference responses 
      i.e. discriminant validity. In the present report, I examined numerous issues
      that undermine the validity of the current tests, and I highlighted various flaws
      in the aspects of these tests and the methodologies pursued. This report
      concludes that the evidence in support of the validity of the plus-maze, the
      light/dark box and the open-field as anxiety tests is poor and methodologically
      questionable. 

PMID- 24910139
TI  - Evidence for altered metabolic pathways during environmental stress: (1)H-NMR
      spectroscopy based metabolomics and clinical studies on subjects of sea-voyage
      and Antarctic-stay.
AB  - The Antarctic context is an analogue of space travel, with close similarity in
      ambience of extreme climate, isolation, constrained living spaces, disrupted
      sleep cycles, and environmental stress. The present study examined the impact of
      the harsh habitat of Antarctica on human physiology and its metabolic pathways,
      by analyzing human serum samples, using (1)H-NMR spectroscopy for identification
      of metabolites; and quantifying other physiological and clinical parameters for
      correlation between expression data and metabolite data. Sera from seven adult
      males (of median age 36years) who participated in this study, from the 28th
      Indian Expeditionary group to the Antarctica station Maitri, were collected in
      chronological sequence. These included: i) baseline control; ii) during ship
      journey; iii) at Antarctica, in the months of March, May, August and November; to
      enable study of temporal evolution of monitored physiological states. 29
      metabolites in serum were identified from the 400MHz (1)H-NMR spectra. Out of
      these, 19 metabolites showed significant variations in levels, during the ship
      journey and the stay at Maitri, compared to the base-line levels. Further
      biochemical analysis also supported these results, indicating that the ship
      journey, and the long-term Antarctic exposure, affected kidney and liver
      functioning. Our metabolite data highlights for the first time the effect of
      environmental stress on the patho-physiology of the human system. Multivariate
      analysis tools were employed for this metabonomics study, using (1)H-NMR
      spectroscopy. 

PMID- 24910140
TI  - Life cycle assessment of a packaging waste recycling system in Portugal.
AB  - Life Cycle Assessment (LCA) has been used to assess the environmental impacts
      associated with an activity or product life cycle. It has also been applied to
      assess the environmental performance related to waste management activities. This
      study analyses the packaging waste management system of a local public authority
      in Portugal. The operations of selective and refuse collection, sorting,
      recycling, landfilling and incineration of packaging waste were considered. The
      packaging waste management system in operation in 2010, which we called
      "Baseline" scenario, was compared with two hypothetical scenarios where all the
      packaging waste that was selectively collected in 2010 would undergo the refuse
      collection system and would be sent directly to incineration (called
      "Incineration" scenario) or to landfill ("Landfill" scenario). Overall, the
      results show that the "Baseline" scenario is more environmentally sound than the
      hypothetical scenarios. 

PMID- 24910141
TI  - Inventory routing for dynamic waste collection.
AB  - We consider the problem of collecting waste from sensor equipped underground
      containers. These sensors enable the use of a dynamic collection policy. The
      problem, which is known as a reverse inventory routing problem, involves
      decisions regarding routing and container selection. In more dense networks, the
      latter becomes more important. To cope with uncertainty in deposit volumes and
      with fluctuations due to daily and seasonal effects, we need an anticipatory
      policy that balances the workload over time. We propose a relatively simple
      heuristic consisting of several tunable parameters depending on the day of the
      week. We tune the parameters of this policy using optimal learning techniques
      combined with simulation. We illustrate our approach using a real life problem
      instance of a waste collection company, located in The Netherlands, and perform
      experiments on several other instances. For our case study, we show that costs
      savings up to 40% are possible by optimizing the parameters. 

PMID- 24910142
TI  - The development of WEEE management and effects of the fund policy for subsidizing
      WEEE treating in China.
AB  - The consumption of electrical and electronic equipment is surging, so is the
      generation of waste electrical and electronic equipment (WEEE). Due to the large
      quantity, high potential risk and valuable capacity of WEEE, many countries are
      taking measures to regulate the management of WEEE. The environmental pollution
      and human health-harming problems caused by irregular treatment of WEEE in China
      make the government pay more and more attention to its management. This paper
      reviews the development of WEEE management in China, introduces the new policy
      which is established for WEEE recycling and especially analyzes the effectiveness
      of the policy, including huge recovery, formation of new recycling system, strict
      supervision to related enterprises, and the stimulation to public awareness.
      Based on the current achievement, some recommendations are given to optimize the
      WEEE management in China. 

PMID- 24910143
TI  - Prognostic factors in localized invasive primary cutaneous malignant melanoma:
      results of a large population-based study.
AB  - BACKGROUND: The prognostic impact of several histopathological prognostic
      features in cutaneous malignant melanoma (CMM) remains controversial. OBJECTIVES:
      To assess the independent prognostic value of mitotic rate, regression, tumour
      infiltrating lymphocytes (TILs) and growth phase in primary stage I and II CMMs.
      METHODS: Clinicohistopathological data were obtained from the Stockholm-Gotland
      registry for 4237 patients diagnosed with an incident primary stage I or II CMM
      followed up to December 2011. The risk of CMM-specific death was evaluated by a
      Cox regression model. RESULTS: A mitotic rate of 1-10 mitoses per mm(2) [hazard
      ratio (HR) 1.69, 95% confidence interval (CI) 1.16-2.45] and > 10 mitoses per
      mm(2) (HR 2.27, 95% CI 1.46-3.52) were significant; TILs and regression were not.
      A more detailed analysis of data assessed between 1989 and 1995 confirmed
      significantly increased HRs for the presence vs. absence of mitoses (HR1-5/mm2
      2.25, 95% CI 1.36-3.76; HR6-10/mm2 2.34, 95% CI 1.23-4.44; HR> 10/mm2 2.64, 95%
      CI 1.39-4.99). Other prognosticators were increasing T-stage vs. T1, presence of
      ulceration and presence of vertical growth phase (VGP). In T1 CMMs, an increasing
      tumour thickness vs. < 0.7 mm (HR0.7-0.8 mm 2.24, 95% CI 1.24-4.04; HR>0.8 mm 
      2.92, 95% CI 1.57-5.43) and presence of ulceration were significantly associated
      with higher HRs; mitotic rate, TILs, regression and growth phase were not.
      CONCLUSIONS: Determinants of increased risk of CMM death in stage I and II CMMs
      were increasing T-stage, presence of ulceration, presence of mitoses and VGP.
      This was not found for TILs or regression.

PMID- 24910144
TI  - Anisotropy modeling of terahertz metamaterials: polarization dependent resonance
      manipulation by meta-atom cluster.
AB  - Recently metamaterials have inspired worldwide researches due to their exotic
      properties in transmitting, reflecting, absorbing or refracting specific
      electromagnetic waves. Most metamaterials are known to have anisotropic
      properties, but existing anisotropy models are applicable only to a single meta
      atom and its properties. Here we propose an anisotropy model for asymmetrical
      meta-atom clusters and their polarization dependency. The proposed anisotropic
      meta-atom clusters show a unique resonance property in which their frequencies
      can be altered for parallel polarization, but fixed to a single resonance
      frequency for perpendicular polarization. The proposed anisotropic metamaterials
      are expected to pave the way for novel optical systems. 

PMID- 24910145
TI  - IL-23R gene polymorphism rs2201841 is associated with psoriatic arthritis.
AB  - We examined rs2201841 within IL-23R gene in Serbian patients with psoriasis and
      healthy controls. G allele frequency was significantly increased in the group of
      patients with psoriatic arthritis compared with controls (0.481 vs 0.308).
      Carriage of G allele increases risk to develop psoriatic arthritis (P = 0.009, OR
      = 3.311, 95% CI 1.29-8.70).

PMID- 24910146
TI  - High-level production of melanin by a novel isolate of Streptomyces kathirae.
AB  - Forty-five bacterial strains that produced diffusive pigments were isolated from
      40 soil samples. Maximum pigment production was from a Streptomyces kathirae
      strain designated SC-1. The diffused pigment was characterized by UV-visual and
      infrared spectroscopy, MS and (1) H nuclear magnetic resonance imaging, and was
      confirmed as melanin. This may be the first report of melanin production by S.
      kathirae. To enhance melanin production, the culture medium was optimized by
      conducting a series of batch fermentations in a defined medium, and the results
      were analysed statistically using a response surface method. The optimal culture
      medium comprised 3.3 g L(-1) amylodextrine, 37 g L(-1) yeast extract, 5 g L(-1)
      NaCl, 0.1 g L(-1) CaCl2 and 54.4 MUM CuSO4 . The pH of this medium was 6.0. Under
      optimal conditions, the melanin concentration was maximized at 13.7 g L(-1) , c.
      8.6-fold higher than obtained in suboptimal medium. To our knowledge, the results
      provide novel data on melanin fermentation, and identify an excellent candidate
      for industrial-scale microbial fermentation of melanin.

PMID- 24910147
TI  - From different neurophysiological methods to conflicting pathophysiological views
      in migraine: a critical review of literature.
AB  - Abnormal increased cortical responsivity to various types of stimuli plays a
      major role in migraine pathogenesis. Neurophysiological studies, however, have
      provided ambiguous findings of either hypo or hyper cortical excitability. This
      is why the term "dysexcitability" has been recently proposed to indicate a more
      general dysregulation of cortical excitability. The aims of this review are: (1)
      to provide existing knowledge and research advances in migraine pathophysiology;
      (2) to propose a unitary interpretation of apparently conflicting
      neurophysiological findings. Data of studies conducted in migraine through
      various evoked potentials techniques and non-invasive brain stimulation methods
      are reviewed, and in some cases reinterpreted according to more recent findings
      on migraine pathophysiology. In particular, we emphasize the concept that various
      methods of testing brain excitability may induce different degrees of cortical
      activation depending on the stimulus parameters used (e.g., intensity, frequency,
      and duration of stimulation), so shedding light on different pathophysiological
      aspects. Finally, we try to reconcile apparently conflicting neurophysiological
      data in the light of a unitary pathophysiological model, suggesting that a
      condition of interictal cortical hyperresponsivity, possibly due to a
      glutamatergic dysfunction, could represent the primum movens of migraine
      pathogenesis. 

PMID- 24910148
TI  - Compatibility of intraoperative 3T MR imaging and intraoperative
      neurophysiological monitoring.

PMID- 24910150
TI  - A brain-computer interface for single-trial detection of gait initiation from
      movement related cortical potentials.
AB  - OBJECTIVE: Applications of brain-computer interfacing (BCI) in
      neurorehabilitation have received increasing attention. The intention to perform
      a motor task can be detected from scalp EEG and used to control rehabilitation
      devices, resulting in a patient-driven rehabilitation paradigm. In this study, we
      present and validate a BCI system for detection of gait initiation using movement
      related cortical potentials (MRCP). METHODS: The templates of MRCP were extracted
      from 9-channel scalp EEG during gait initiation in 9 healthy subjects.
      Independent component analysis (ICA) was used to remove artifacts, and the
      Laplacian spatial filter was applied to enhance the signal-to-noise ratio of
      MRCP. Following these pre-processing steps, a matched filter was used to perform
      single-trial detection of gait initiation. RESULTS: ICA preprocessing was shown
      to significantly improve the detection performance. With ICA preprocessing,
      across all subjects, the true positive rate (TPR) of the detection was 76.9+/
      8.97%, and the false positive rate was 2.93+/-1.09 per minute. CONCLUSION: The
      results demonstrate the feasibility of detecting the intention of gait initiation
      from EEG signals, on a single trial basis. SIGNIFICANCE: The results are
      important for the development of new gait rehabilitation strategies, either for
      recovery/replacement of function or for neuromodulation.

PMID- 24910151
TI  - Expression of the T cell-specific adapter protein in human tissues.
AB  - T cell-specific adapter protein (TSAd) encoded by the SH2D2A gene is expressed in
      activated T cells, NK cells and endothelial cells, but its tissue expression has
      not yet been mapped. Here, we have defined the specificity of two commercially
      available anti-TSAd monoclonal reagents using peptide arrays. We found them to
      bind separate epitopes in the C-terminal part of TSAd. We then used
      immunohistochemistry to examine TSAd expression in various human lymphoid and non
      lymphoid tissues. Immunostaining of adjacent tissue sections revealed that a
      substantial fraction of CD3-positive cells in normal lymphoid and non-lymphoid
      tissues expressed TSAd. In particular, essentially all intra-epithelial T cells
      appeared to coexpress TSAd. In addition, TSAd expression was observed in
      endothelial cells of dermal microvessels, while it was not detected in
      endothelial cells of the other tested tissues. This work provides insight into
      the expression pattern of TSAd in various healthy human tissues. 

PMID- 24910152
TI  - Altered microRNA expression in inflamed and non-inflamed terminal ileal mucosa of
      adult patients with active Crohn's disease.
AB  - BACKGROUND AND AIMS: MicroRNAs (miRNAs) play an important role in inflammation.
      Several studies have reported the unique miRNA profiles in colonic mucosa and
      peripheral blood of patients with active Crohn's disease (CD). But there is
      limited data about the miRNA profiles of the terminal ileum, the most commonly
      involved location, especially the non-inflamed mucosa. We aimed to investigate
      the miRNA expression of both inflamed and non-inflamed terminal ileal mucosa in
      adult patients with active CD. METHODS: Total RNA of all mucosal samples was
      extracted. MiRNA expression profile was assessed using microarray technology, and
      then selected miRNAs were evaluated using quantitative reverse-transcription
      polymerase chain reaction (qRT-PCR) to confirm the results of the microarray
      investigation. RESULTS: Sixteen CD patients and 10 healthy adults were included.
      Samples of six patients and six controls were used for the microarray analysis.
      Samples of all participants were used for the validation of qRT-PCR. Results of
      the microarray showed miRNA expressions of both inflamed and non-inflamed mucosa
      were altered compared with controls. The differential expressions of hsa-miR-192
      5p, hsa-miR-495-5p, hsa-let-7b-5p, hsa-miR-361-3p, and hsa-miR-124-3p were
      confirmed by qRT-PCR. CONCLUSION: Both inflamed and non-inflamed terminal ileal
      mucosa in adult patients with active CD have their distinct miRNA expression
      patterns compared with healthy controls. Dysregulated miRNAs may be responsible
      for pathogenesis of CD.

PMID- 24910149
TI  - Real-time processing in picture naming in adults who stutter: ERP evidence.
AB  - OBJECTIVE: The aim was to compare real-time language/cognitive processing in
      picture naming in adults who stutter (AWS) versus typically-fluent adults (TFA).
      METHODS: Participants named pictures preceded by masked prime words. Primes and
      target picture labels were identical or mismatched. Priming effects on naming and
      picture-elicited ERP activity were analyzed. Vocabulary knowledge correlations
      with these measures were assessed. RESULTS: Priming improved naming RTs and
      accuracy in both groups. RTs were longer for AWS, and correlated positively with
      receptive vocabulary in TFA. Electrophysiologically, posterior-P1 amplitude
      negatively correlated with expressive vocabulary in TFA versus receptive
      vocabulary in AWS. Frontal/temporal-P1 amplitude correlated positively with
      expressive vocabulary in AWS. Identity priming enhanced frontal/posterior-N2
      amplitude in both groups, and attenuated P280 amplitude in AWS. N400 priming was
      topographically-restricted in AWS. CONCLUSIONS: Results suggest that conceptual
      knowledge was perceptually-grounded in expressive vocabulary in TFA versus
      receptive vocabulary in AWS. Poorer expressive vocabulary in AWS was potentially
      associated with greater suppression of irrelevant conceptual information. Priming
      enhanced N2-indexed cognitive control and visual attention in both groups. P280
      indexed focal attention attenuated with priming in AWS only. Topographically
      restricted N400 priming suggests that lemma/word form connections were weaker in
      AWS. SIGNIFICANCE: Real-time language/cognitive processing in picture naming
      operates differently in AWS.

PMID- 24910153
TI  - Complete tribal sampling reveals basal split in Muscidae (Diptera), confirms
      saprophagy as ancestral feeding mode, and reveals an evolutionary correlation
      between instar numbers and carnivory.
AB  - With about 5000 species in ca. 180 genera, the Muscidae is the most species-rich
      family in the muscoid grade of Calyptratae (Diptera: Cyclorrhapha), the others
      being the Fanniidae, Scathophagidae and Anthomyiidae. Muscidae is remarkable for
      its young age, high species diversity in all biogeographic regions, and an
      unusually diverse range of feeding habits at the larval stage (e.g., saprophagy,
      phytophagy, carnivory, endoparasitism, haematophagy). We here review muscid
      classification and biology and present a molecular phylogeny based on four
      mitochondrial genes (12S, 16S, COI, CYTB) and three nuclear genes (28S, Ef1a, and
      CAD) for 84 species from 40 genera. Our analysis is the first to include species
      from all biogeographic regions and all currently recognised muscid subfamilies
      and tribes. We provide strong support for the monophyly of the Muscidae, and for
      the first time also for the first split within this family. The ancestral larval
      feeding habit is reconstructed to be saprophagy with more specialised
      coprophagous saprophagy, phytophagy, and carnivory evolving multiple times from
      saprophagous ancestors. The origins of carnivory in larvae are significantly
      correlated with a reduction of the number of larval instars from three
      (ancestral) to two and one. The genus Achanthiptera which was previously in its
      own subfamily is shown to be closely related to Azeliini. However, it appears
      that Azeliinae is paraphyletic because Muscinae is sister-group to the Azeliini
      while the azeliine Reinwardtiini are polyphyletic. Coenosiinae and Muscinae are
      monophyletic, but Muscini is paraphyletic with regard to Stomoxyini. Because many
      subfamilies are apparently para- or even polyphyletic, we review the history of
      muscid classification in order to reveal how the currently used classification
      originated. 

PMID- 24910154
TI  - The impact of calibration and clock-model choice on molecular estimates of
      divergence times.
AB  - Phylogenetic estimates of evolutionary timescales can be obtained from nucleotide
      sequence data using the molecular clock. These estimates are important for our
      understanding of evolutionary processes across all taxonomic levels. The
      molecular clock needs to be calibrated with an independent source of information,
      such as fossil evidence, to allow absolute ages to be inferred. Calibration
      typically involves fixing or constraining the age of at least one node in the
      phylogeny, enabling the ages of the remaining nodes to be estimated. We conducted
      an extensive simulation study to investigate the effects of the position and
      number of calibrations on the resulting estimate of the timescale. Our analyses
      focused on Bayesian estimates obtained using relaxed molecular clocks. Our
      findings suggest that an effective strategy is to include multiple calibrations
      and to prefer those that are close to the root of the phylogeny. Under these
      conditions, we found that evolutionary timescales could be estimated accurately
      even when the relaxed-clock model was misspecified and when the sequence data
      were relatively uninformative. We tested these findings in a case study of simian
      foamy virus, where we found that shallow calibrations caused the overall
      timescale to be underestimated by up to three orders of magnitude. Finally, we
      provide some recommendations for improving the practice of molecular-clock
      calibration. 

PMID- 24910155
TI  - Towards a mitogenomic phylogeny of Lepidoptera.
AB  - The backbone phylogeny of Lepidoptera remains unresolved, despite strenuous
      recent morphological and molecular efforts. Molecular studies have focused on
      nuclear protein coding genes, sometimes adding a single mitochondrial gene.
      Recent advances in sequencing technology have, however, made acquisition of
      entire mitochondrial genomes both practical and economically viable. Prior
      phylogenetic studies utilised just eight of 43 currently recognised lepidopteran
      superfamilies. Here, we add 23 full and six partial mitochondrial genomes
      (comprising 22 superfamilies of which 16 are newly represented) to those
      publically available for a total of 24 superfamilies and ask whether such a
      sample can resolve deeper lepidopteran phylogeny. Using recoded datasets we
      obtain topologies that are highly congruent with prior nuclear and/or
      morphological studies. Our study shows support for an expanded Obtectomera
      including Gelechioidea, Thyridoidea, plume moths (Alucitoidea and Pterophoroidea;
      possibly along with Epermenioidea), Papilionoidea, Pyraloidea, Mimallonoidea and
      Macroheterocera. Regarding other controversially positioned higher taxa, Doidae
      is supported within the new concept of Drepanoidea and Mimallonidae sister to (or
      part of) Macroheterocera, while among Nymphalidae butterflies, Danainae and not
      Libytheinae are sister to the remainder of the family. At the deepest level, we
      suggest that a tRNA rearrangement occurred at a node between Adeloidea and
      Ditrysia+Palaephatidae+Tischeriidae. 

PMID- 24910156
TI  - A re-evaluation of phylogenetic relationships within reed warblers (Aves:
      Acrocephalidae) based on eight molecular loci and ISSR profiles.
AB  - Acrocephalidae is the most monomorphic family among passerines and has seen a
      long history of different classifications and successive revisions. In this
      study, we evaluated the phylogenetic relationships among 35 species of
      Acrocephalidae based on DNA sequences from five nuclear loci (MB, ODC, LDH, FIB5
      and RAG-1), three mitochondrial genes (CYB, ND2 and COI) and genomic
      fingerprinting with ISSR-PCR. We could improve the resolution of phylogenetic
      relationships among many species, but despite the use of 6280 nucleotides, some
      deep-level relationships remain enigmatic. Lack of nodal support at some branches
      may be the result of rapid radiation. The last common ancestor of this family
      dated for the Middle Miocene (14 MYA). In agreement with previous studies, we
      recovered the major clades of Acrocephalus, Iduna (except I. aedon), Hippolais,
      Nesillas and Calamonastides. We accept the current taxonomic position of
      Calamonastides gracilirostris as a monotypic genus and the inclusion of Iduna
      natalensis and I. similis within Iduna but phylogenetic analyses based on
      mitochondrial and nuclear genes as well as ISSR profiles did not support the
      position of I. aedon in Iduna. Therefore, we resurrect the former genus
      Phragamaticola for this species in order to avoid paraphyletic clades. 

PMID- 24910157
TI  - Together - a couples' program to improve communication, coping, and financial
      management skills: development and initial pilot-testing.
AB  - The accumulated knowledge about the negative impact of financial strain on
      couple's relationship functioning and the magnitude of the latest economic
      downturn have brought together the fields of financial counseling and couples'
      therapy. This article describes the development of a new interdisciplinary
      program that aims at helping couples under financial strain improve their
      financial management, communication, and dyadic coping skills. The article also
      reports the results from its initial pilot-testing with data collected from 18
      financially distressed couples before and after participation in the program and
      3 months later. Results from repeated measures ANOVAs suggest that the program
      may help reduce both partners' financial strain and the male negative
      communication and improve both partners' financial management skills and
      strategies to cope together with financial strain, and the male relationship
      satisfaction. These findings together with the high satisfaction reported by
      participants regarding the structure and content of the sessions and homework
      suggest that this program may be a promising approach to help couples
      experiencing financial strain. Gender differences, clinical implications, and
      possibilities for further research are also discussed.

PMID- 24910158
TI  - The use of tetanus post-exposure prophylaxis guidelines by general practitioners
      and emergency departments in the Netherlands: a cross-sectional questionnaire
      study.
AB  - BACKGROUND: The Dutch National Immunisation Programme includes six tetanus toxoid
      (TT) vaccinations and reaches a high rate of vaccination coverage. In the
      Netherlands, several guidelines related to tetanus post-exposure prophylaxis (T
      PEP) are in place. In 2003, the Dutch Health Council (HC) reviewed the use of T
      PEP. The aim of this study is to evaluate whether the HC recommendations have
      been implemented. METHODS: We asked 178 Dutch General Practitioner (GP) offices
      and 60 Emergency Departments (EDs) to participate in a cross-sectional
      questionnaire study and requested that participating facilities send in the T-PEP
      guidelines adopted by their practice. The differences, based on categories
      mentioned in the HC recommendations, between GPs and EDs and the type of T-PEP
      guidelines adopted were assessed. RESULTS: The response rates for the GPs and EDs
      were 38% (n=67) and 70% (n=42), respectively. 98% percent (n=107) of the
      participants reported having T-PEP guidelines. Of the guidelines described in the
      survey responses, 28% (n=23; EDs 41%, GPs 21%) were consistent with the HC
      recommendations, 36% (n=29; EDs 7%, GPs 52%) adhered to the guidelines of the
      College of GPs (CGP), which restricts the use of T-PEP to tetanus prone wounds
      but for these wounds is in line with the recommendations of the HC. The remaining
      36% had adopted other guidelines, most of which can lead to over-prescription of
      T-PEP. Information on T-PEP was lacking in patients with higher risk vaccination
      histories. CONCLUSION: Almost all participants have adopted T-PEP guidelines.
      Strict adherence to the HC recommendations is low. More than half of GPs have
      adopted the more restrictive CGP-guideline, which limits T-PEP to tetanus prone
      wounds.

PMID- 24910159
TI  - Application of a motion capture data glove for hand and wrist ergonomic analysis
      during laparoscopy.
AB  - OBJECTIVES: This study aims to analyze the surgeons' hand spatial configuration
      during the use of two different instrument handles for laparoscopy, by obtaining
      information from the data glove CyberGlove(r), and establishing existing risk
      levels for wrist disorders. MATERIAL AND METHODS: Fifty surgeons participated in
      this study and were distributed into three groups (novices, intermediate and
      experts). Each subject carried out suturing and dissection tasks on a physical
      simulator, using axial-handled or ring-handled instruments, respectively. Hand
      and wrist positions were registered by the CyberGlove(r) and a modified RULA
      method was applied to establish appropriate risk levels for wrist disorders.
      RESULTS: We found statistically significant differences in seven of the eleven
      glove sensors when comparing both tasks. RULA method showed that all subjects,
      with the exception of the experts using an axial-handled instrument, assume a
      prejudicial wrist posture during the practice of suturing and dissection tasks on
      the simulator. CONCLUSIONS: Data glove CyberGlove(r) allows for the distinction
      between two laparoscopic exercises performed with different instruments. Also,
      laparoscopic intracorporeal suturing when performed with an axial-handled needle
      holder entails a more ergonomic posture for the wrist joint. Previous minimally
      invasive surgical experience is a positive influencing factor on the surgeons'
      wrist postures during laparoscopy.

PMID- 24910160
TI  - Long-term consequences of maternal overweight in pregnancy on offspring later
      health: findings from the Helsinki Birth Cohort Study.
AB  - INTRODUCTION: Obesity has reached epidemic proportions worldwide. Maternal
      obesity has consequences for the offspring's later health. Only few studies have
      focused upon the long-term consequences of maternal obesity on the offspring's
      later health. METHODS: A total of 13,345 men and women born in Helsinki during
      1934-44 belonging to the Helsinki Birth Cohort Study were included in the study.
      Data on maternal weight and height in late pregnancy were available from hospital
      records. Using validated national registers we report on the following outcomes
      in relation to maternal BMI: death, cancer, coronary heart disease, stroke, and
      diabetes among the offspring. RESULTS: Maternal BMI was positively associated
      with each of the later health outcomes of the offspring. The associations were
      strongest for cardiovascular disease and type 2 diabetes. The association with
      type 2 diabetes was stronger in women. DISCUSSION: Our findings stress the
      importance of early prevention of overweight and obesity in women of child
      bearing age.

PMID- 24910161
TI  - A randomized controlled trial of burping for the prevention of colic and
      regurgitation in healthy infants.
AB  - BACKGROUND: Efficacy of burping in lowering colic and regurgitation episodes in
      healthy term babies lacks evidence in literature. METHODS: We conducted a
      randomized controlled trial to compare efficacy of burping versus no-burping in
      71 mother-baby dyads in community setting. Primary outcome was reduction in event
      rates of colic and regurgitation episodes over 3 months. RESULTS: Baseline
      characteristics were similar in two groups. Difference in incidence rates of
      colic between the control and burping group was 1.57 episodes/infant/100 weeks
      [95% confidence interval (CI): -0.63 to 3.76]. There was statistically no
      significant reduction in colic episodes between burping and non-burping study
      subjects during 3 months of follow-up (adjusted relative risk 0.64; 95% CI: 0.22
      1.86, P-value 0.41). Incidence rate difference of regurgitation
      episodes/infant/week between burping and control group was 4.36 (95% CI: 4.04 to
      4.69) and there was statistically significant increase in burping group (adjusted
      relative risk 2.05; 95% CI: 1.92-2.18, P-value < 0.0001). CONCLUSIONS: Although
      burping is a rite of passage, our study showed that burping did not significantly
      lower colic events and there was significant increase in regurgitation episodes
      in healthy term infants up to 3 months of follow-up.

PMID- 24910162
TI  - Ethical Issues in Adolescents' Sexual and Reproductive Health Research in
      Nigeria.
AB  - There is increasing interest in the need to address the ethical dilemmas related
      to the engagement of adolescents in sexual and reproductive health (SRH)
      research. Research projects, including those that address issues related to STIs
      and HIV, adverse pregnancy outcomes, violence, and mental health, must be
      designed and implemented to address the needs of adolescents. Decisions on when
      an individual has adequate capacity to give consent for research most commonly
      use age as a surrogate rather than directly assessing capacity to understand the
      issues and make an informed decision on whether to participate in research or
      not. There is a perception that adolescents participating in research are more
      likely to be coerced and may therefore not fully comprehend the risk they may be
      taking when engaging in research. This paper examines the various ethical issues
      that may impact stakeholders' decision making when considering engaging
      adolescents in SRH research in Nigeria. It makes a case for lowering the age of
      consent for adolescents. While some experts believe it is possible to extrapolate
      relevant information from adult research, studies on ethical aspects of
      adolescents' participation in research are still needed, especially in the field
      of sexual and reproductive health where there are often differences in knowledge,
      attitudes and practices compared to adults. The particular challenges of applying
      the fundamental principles of research ethics to adolescent research, especially
      research about sex and sexuality, will only become clear if more studies are
      conducted. 

PMID- 24910163
TI  - Evaluating the success of Nd: YAG laser ablation in the treatment of recalcitrant
      verruca plantaris and a cautionary note about local anaesthesia on the plantar
      aspect of the foot.
AB  - BACKGROUND: There are various methods advocated for the treatment of verruca
      plantaris. However, many verrucas do not respond to simple treatment. OBJECTIVE:
      This study presents our results using Nd: YAG laser ablation therapy for such
      recalcitrant cases. METHODS: We performed a retrospective audit by sending a
      questionnaire to all patients with recalcitrant verrucas who had been treated
      with Nd:YAG laser ablation over the previous 12 months. The questionnaire asked
      whether treatment had been successful, successful but new lesions had emerged,
      partially successful with improvement or unsuccessful. A Fontana Nd:YAG laser was
      used at the following specifications; long pulsed mode with pulse width 25 ms,
      frequency 1.0 Hz; fluence 240 J/cm(2) and spot size 2 mm. Some patients requested
      local anaesthesia and had direct infiltration with 0.5% plain lidocaine. RESULTS:
      Fifty-three of the original 87 patients responded (60.9% response rate) with a
      male to female ratio of 24:29, mean age of 47 years and an age range between 22
      72. Thirty-seven patients reported complete success post treatment (69.8%) and a
      further five reported improvement. The remaining 11 felt their treatment was
      unsuccessful. The cure rate was 81.8% in unilateral single cases, 68.1% in
      unilateral multiple cases and 65% in bilateral cases. Ten patients requested
      sublesional lidocaine injections of which 4 had skin breakdown after Nd: YAG
      ablation. CONCLUSION: Nd:YAG laser ablation is effective in the treatment of
      recalcitrant verruca plantaris. However, we caution against the use of direct
      local anaesthesia infiltration before laser treatment.

PMID- 24910164
TI  - Nitric oxide is necessary for labilization of a consolidated context memory
      during reconsolidation in terrestrial snails.
AB  - Nitric oxide (NO) is known to be involved in associative memory formation. We
      investigated the influence of blocking NO function on the reconsolidation of
      context memory in terrestrial snails (Helix lucorum L.). After a 10 day session
      of electric shocks in one context only, context memory in snails was observed in
      test sessions as the significant difference of amplitudes of withdrawal responses
      to tactile stimuli in two different contexts. After a 1 day rest, a session of
      'reminding' was performed, preceded by injection in different groups of the
      snails with either vehicle or combination of the protein synthesis blocker
      anisomycin (ANI) with one of the following drugs: the NO scavenger carboxy-PTIO,
      the NO-synthase inhibitors N-omega-nitro-L-arginin, nitroindazole and NG-nitro-L
      arginine methyl ester hydrochloride, or the NO donor S-nitroso-N-acetyl-DL
      penicillamine. Testing the context memory at different time intervals after the
      reminder under ANI injection showed that the context memory was impaired at 24 h
      and later, whereas the reminder under combined injection of ANI and each of the
      NO-synthase inhibitors used or the NO scavenger showed no impairment of long-term
      context memory. Injection of the NO donor S-nitroso-N-acetyl-DL-penicillamine
      with or without reminder had no effect on context memory. The results obtained
      demonstrated that NO is necessary for labilization of a consolidated context
      memory.

PMID- 24910165
TI  - Diffusion restriction in a non-enhancing metastatic brain tumor treated with
      bevacizumab - recurrent tumor or atypical necrosis?
AB  - A 38-year-old female with metastatic brain cancer developed non-enhancing,
      diffusion restricted lesions following bevacizumab treatment. From our review of
      the literature, this is the first reported case of this type of lesion.
      Clinicians should be wary of these lesions, as they can represent either tumor
      progression or necrosis/effects of chronic hypoxia from anti-angiogenic therapy.
      Further investigation is necessary to determine the biological mechanism and
      clinical significance of this type of imaging appearance. 

PMID- 24910166
TI  - Offending outcomes of a mental health youth diversion pilot scheme in England.
AB  - BACKGROUND: A youth justice diversion scheme designed to enhance health provision
      for young people with mental health and developmental problems as soon as they
      enter the youth justice system has been piloted in six areas of England. AIM: As
      part of a wider evaluation of the first youth justice diversion scheme outside
      the USA, our aim here was to examine re-offending. We sought to test the
      hypothesis that a specialised service for young people with mental health
      difficulties would be associated with reductions in re-offending. In addition, we
      examined factors associated with the re-offending that occurred. METHODS: Two
      hundred and eight young offenders with access to the diversion scheme and 200
      without were compared in four geographical area pairings to allow for socio
      demographic contextual differences. Officially recorded re-offending was
      ascertained for 15-30 months after study entry. We also tested characteristics
      associated with re-offending among everyone entering the diversion scheme (n =
      870). RESULTS: There was no statistically significant difference in re-offending
      rates between the diversion and comparison samples, but those with access to
      diversion had significantly longer periods of desistance from offending than
      those who did not. In multivariate analysis, the only significant characteristic
      associated with re-offending was history of previous offending. CONCLUSIONS:
      Prevention of re-offending is only one of the potentially beneficial outcomes of
      diversion of young people who are vulnerable because of mental health problems,
      but it is an important one. The advantage of longer survival without prevention
      of re-offending suggests that future research should explore critical timings for
      these young people. The equivocal nature of the findings suggests that a
      randomised controlled trial would be justified.

PMID- 24910167
TI  - Equilibrium phases of one-patch colloids with short-range attractions.
AB  - Inspired by experimental studies of short-ranged attractive patchy particles, we
      study with computer simulations the phase behavior and the crystalline structures
      of one-patch colloids with an interaction range equal to 5% of the particle
      diameter. In particular, we study the effects of the patch surface coverage
      fraction, defined as the ratio between the attractive and the total surface of a
      particle. Using free-energy calculations and thermodynamic integration schemes,
      we evaluate the equilibrium phase diagrams for particles with patch coverage
      fractions of 30%, 50% and 60%. For a 60% surface coverage fraction, we observe
      stable lamellar crystals consisting of stacked bilayers that directly coexist
      with a low density fluid. Inside the coexistence region, we observe the formation
      of lamellar structures also in direct NVT simulations, indicating that the
      barrier of formation is low and experimental realization is feasible. For
      sufficiently strong interactions, these structures spontaneously assemble from
      the fluid in simulations, suggesting that they might also easily form in
      experimental systems. In the Janus case, i.e. at 50% surface coverage fraction,
      no lamellar structures are formed, and the stable crystals are similar to those
      that have been found previously for a longer interaction range (i.e. 20% of the
      particle diameter). At 30% coverage fraction, we identify novel 'open' crystal
      structures with large unit cells of up to 14 particles that are stable in the
      strong interaction limit. 

PMID- 24910168
TI  - Evidence and conjecture about mechanisms of cutaneous disease in
      photodermatology.
AB  - Photosensitivity disorders are caused by a variety of mechanisms. Three common
      themes are as follows: excess chromophore allowing visible light energy to cause
      photodynamic damage, reduced DNA repair capacity to UV-induced DNA damage, and
      enhanced sensitivity to light-induced allergens mediated immunologically.
      Although the cause of each condition may be known, the precise pathogenesis
      underlying the photosensitivity has taken longer to understand. By focussing on
      three clinical disorders under each of these themes, we have explored the
      following: why erythropoietic protoporphyria differs so markedly from the other
      cutaneous porphyrias; how a DNA repair defect was eventually revealed to be the
      underlying cause of the vitamin B3 deficiency disorder of pellagra; an
      immunological explanation for the over reactivity to photoallergens in chronic
      actinic dermatitis. 

PMID- 24910170
TI  - Allometric scaling of indirect effects: body size ratios predict non-consumptive
      effects in multi-predator systems.
AB  - Non-consumptive effects (NCES) frequently lead to non-independent effects of
      multiple predators. While such emergent predator effects are ubiquitous in
      natural communities, the strength of these effects varies among studies and
      systems, making it difficult to predict a priory how changes in predator
      diversity influence prey suppression. Thus, identifying general scaling rules
      which can explain this variation of non-independent effects is vital for
      modelling natural communities and how they respond to biodiversity loss. Body
      size is a key trait determining the nature and strength of ecological
      interactions. While great progress has been made using allometric relationships
      to predict the interaction strength of predator-prey pairs, it is unknown whether
      similar relationships explain variation in the strength of NCEs, and how they are
      related to consumptive effects. Here, we experimentally manipulate the relative
      size difference of multiple predators to determine whether NCEs follow general
      allometric scaling relationships in an aquatic multi-predator system. Results
      demonstrate that the presence and strength of NCEs can vary dramatically across
      predator combinations. However, this variation scaled predictably with the size
      ratio of predators, increasing the size difference among predators increased
      NCEs. This pattern was driven by a size-mediated shift in 'food web motif' from
      competition to intraguild predation and a positive correlation of NCEs and
      intraguild predation rate. Results indicate that models which assume that
      consumers have independent effects are particularly likely to make erroneous
      predictions when predators differ substantially in size, but simple allometric
      relationships of NCEs could be used to correct this bias. 

PMID- 24910171
TI  - An insight into the sensitivity of maize to photoperiod changes under controlled
      conditions.
AB  - Response of maize to photoperiods affects adaption of this crop to environments.
      We characterize the phenotypes of four temperate-adapted maize foundation
      parents, Huangzao 4, Chang 7-2, Ye 478 and Zheng 58, and two tropically adapted
      maize foundation parents, M9 and Shuang M9 throughout the growth stage under
      three constant photoperiod regimes in a daily cycle of 24 h at 28  degrees C, and
      analysed expression of 48 photoperiod response-associated genes. Consequently,
      long photoperiod (LP) repressed development of the tassels of photoperiod
      sensitive maize lines at V9 stage, and caused subsequent failure in flowering;
      failure of photoperiod-sensitive maize lines in flowering under LP was associated
      with lower expression of flowering-related genes; photoperiod changes could make
      a marked impact on spatial layout of maize inflorescence. The larger oscillation
      amplitude of expression of photoperiod-responsive genes occurred in LP-sensitive
      maize lines. In conclusion, failure in development of tassels at V9 stage under
      LP is an early indicator for judging photoperiod sensitivity. The adaptation of
      temperate-adapted maize lines to LP is due to the better coordination of
      expression among photoperiod-sensing genes instead of the loss of the genes. High
      photoperiod sensitivity of maize is due to high expression of circadian rhythm
      responding genes improperly early in the light.

PMID- 24910169
TI  - Naturalistic rodent models of chronic early-life stress.
AB  - A close association between early-life experience and cognitive and emotional
      outcomes is found in humans. In experimental models, early-life experience can
      directly influence a number of brain functions long-term. Specifically, and often
      in concert with genetic background, experience regulates structural and
      functional maturation of brain circuits and alters individual neuronal function
      via large-scale changes in gene expression. Because adverse experience during
      sensitive developmental periods is often associated with neuropsychiatric
      disease, there is an impetus to create realistic models of distinct early-life
      experiences. These can then be used to study causality between early-life
      experiential factors and cognitive and emotional outcomes, and to probe the
      underlying mechanisms. Although chronic early-life stress has been linked to the
      emergence of emotional and cognitive disorders later in life, most commonly used
      rodent models of involve daily maternal separation and hence intermittent early
      life stress. We describe here a naturalistic and robust chronic early-life stress
      model that potently influences cognitive and emotional outcomes. Mice and rats
      undergoing this stress develop structural and functional deficits in a number of
      limbic-cortical circuits. Whereas overt pathological memory impairments appear
      during adulthood, emotional and cognitive vulnerabilities emerge already during
      adolescence. This naturalistic paradigm, widely adopted around the world,
      significantly enriches the repertoire of experimental tools available for the
      study of normal brain maturation and of cognitive and stress-related disorders
      including depression, autism, post-traumatic stress disorder, and dementia.

PMID- 24910173
TI  - Enterovirus infections are associated with white matter damage in neonates.
AB  - AIM: To explore the imaging findings of neonatal infants infected with
      enteroviruses. METHODS: A retrospective study was conducted on 12 patients who
      were diagnosed with encephalitis caused by enterovirus. Clinical presentation,
      cranial ultrasonography (cUS), magnetic resonance imaging (MRI) findings and
      neurodevelopment outcome of 12 cases were analysed. RESULTS: Twelve infants, with
      a gestational age of 35 to 39 weeks, presented at 36 to 41 weeks postmenstrual
      age with clinical symptoms of enterovirus infections. Ten of 12 neonatal infants
      had a fever and 4 of 12 presented with a sepsis-like illness. cUS in one preterm
      infant showed periventricular echogenicity. Neonatal MRI confirmed white matter
      changes in 12 infants. Follow-up of infants were 18 months. Outcome was variable
      with cerebral palsy in 2 infants and normal neurodevelopment outcome in 10
      infants. CONCLUSIONS: Enterovirus may cause severe central nervous system
      infection in the neonatal period. The neuroimaging studies are informative and
      should be a part of care for infants with enteroviruses.

PMID- 24910176
TI  - Spontaneous healing responses detected by cone-beam computed tomography of
      horizontal root fractures: a report of two cases.
AB  - Horizontal root fractures (HRF) usually affect the anterior teeth as a result of
      trauma, and generally heal spontaneously, depending on the vitality of the pulp.
      Diagnosis based on clinical findings, sensitivity tests, and radiographic
      examination is important to determine the presence of a root fracture and to
      prevent a root fracture from passing unnoticed. Cone-beam computed tomography
      (CBCT) has been used successfully for diagnosis and prognosis imaging of root
      fractures and has proved to be superior to other radiographic methods. This study
      reports two cases of dental trauma caused by a collision and a sports accident.
      The patients suffered horizontal root fractures in the maxillary left central
      incisor and in the mandibular left central incisor. The diagnosis of root
      fracture was confirmed by cone-beam computed tomography (CBCT) images, which also
      demonstrated spontaneous healing of the fracture line. The repair occurred by
      interposition of connective tissue in the former case and by interposition of
      bone and connective tissue in the latter case. The final diagnoses of both cases
      were based on CBCT images, indicating the importance of a CBCT examination to
      reach a firm diagnosis and to follow the healing process of root fracture cases,
      avoiding unnecessary radical endodontic treatment.

PMID- 24910177
TI  - Pulmonary arterial hypertension associated with impaired lysosomal endothelin-1
      degradation.
AB  - We report on a boy with severe pulmonary arterial hypertension associated with
      mucolipidosis, a rare lysosomal storage disorder. During diagnostic
      catheterisation, we found increased endothelin-1 levels, but normal big
      endothelin-1-levels (the precursor form of endothelin-1), which suggests impaired
      degradation of endothelin-1 rather than increased synthesis. As endothelin-1
      degradation takes place in the lysosome, it appears likely that lysosomal
      dysfunction caused by the underlying disease contributes to the development of
      pulmonary arterial hypertension in this patient. 

PMID- 24910172
TI  - Estimation of diagnostic test accuracy without full verification: a review of
      latent class methods.
AB  - The performance of a diagnostic test is best evaluated against a reference test
      that is without error. For many diseases, this is not possible, and an imperfect
      reference test must be used. However, diagnostic accuracy estimates may be biased
      if inaccurately verified status is used as the truth. Statistical models have
      been developed to handle this situation by treating disease as a latent variable.
      In this paper, we conduct a systematized review of statistical methods using
      latent class models for estimating test accuracy and disease prevalence in the
      absence of complete verification.

PMID- 24910174
TI  - Neonatal rhinovirus induces mucous metaplasia and airways hyperresponsiveness
      through IL-25 and type 2 innate lymphoid cells.
AB  - BACKGROUND: Early-life human rhinovirus infection has been linked to asthma
      development in high-risk infants and children. Nevertheless, the role of
      rhinovirus infection in the initiation of asthma remains unclear. OBJECTIVE: We
      hypothesized that, in contrast to infection of mature BALB/c mice, neonatal
      infection with rhinovirus promotes an IL-25-driven type 2 response, which causes
      persistent mucous metaplasia and airways hyperresponsiveness. METHODS: Six-day
      old and 8-week-old BALB/c mice were inoculated with sham HeLa cell lysate or
      rhinovirus. Airway responses from 1 to 28 days after infection were assessed by
      using quantitative PCR, ELISA, histology, immunofluorescence microscopy, flow
      cytometry, and methacholine responsiveness. Selected mice were treated with a
      neutralizing antibody to IL-25. RESULTS: Compared with mature mice, rhinovirus
      infection in neonatal mice increased lung IL-13 and IL-25 production, whereas IFN
      gamma, IL-12p40, and TNF-alpha expression was suppressed. In addition, the
      population of IL-13-secreting type 2 innate lymphoid cells (ILC2s) was expanded
      with rhinovirus infection in neonatal but not mature mice. ILC2s were the major
      cell type secreting IL-13 in neonates. Finally, anti-IL-25 neutralizing antibody
      attenuated ILC2 expansion, mucous hypersecretion, and airways responsiveness.
      CONCLUSIONS: These findings suggest that early-life viral infection could
      contribute to asthma development by provoking age-dependent, IL-25-driven type 2
      immune responses.

PMID- 24910175
TI  - Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23
      in patients with psoriasis.
AB  - BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a major proallergic cytokine
      that promotes TH2 responses through dendritic cell (DC) activation. Whether it
      also plays a role in human autoimmune inflammation and associated pathways is not
      known. OBJECTIVE: In this study we investigated the potential role of several
      epithelium-derived factors, including TSLP, in inducing IL-23 production by human
      DCs. We further dissected the role of TSLP in patients with psoriasis, an IL-23
      associated skin autoimmune disease. METHODS: The study was performed in human
      subjects using primary cells and tissue samples from patients with psoriasis and
      healthy donors. We analyzed the production of IL-23 in vitro by blood and skin
      DCs. We studied the function for TSLP and its interaction with other components
      of the inflammatory microenvironment in situ and ex vivo. RESULTS: We found that
      TSLP synergized with CD40 ligand to promote DC activation and pathogenic IL-23
      production by primary blood and skin DCs. In situ TSLP was strongly expressed by
      keratinocytes of untreated psoriatic lesions but not in normal skin. Moreover, we
      could demonstrate that IL-4, an important component of the TH2 inflammation seen
      in patients with atopic dermatitis, inhibited IL-23 production induced by TSLP
      and CD40 ligand in a signal transducer and activator of transcription 6
      independent manner. CONCLUSION: Our results identify TSLP as a novel player
      within the complex psoriasis cytokine network. Blocking TSLP in patients with
      psoriasis might contribute to decreasing DC activation and shutting down the
      production of pathogenic IL-23.

PMID- 24910178
TI  - [Assessment of concordance between CAM-ICU scale and nursing delirium scale in
      postoperative period of ICU patients after cardiac surgery].
AB  - OBJECTIVE: To evaluate concordance between the scale of delirium assessment CAM
      ICU and the Nursing Delirium Screening Scale (NDSS) in postoperative cardiac
      surgery. MATERIAL AND METHODS: Prospective study in tertiary hospital with
      consecutive selection of patients after cardiac surgery. During the stay in the
      Intensive Care Unit, CAM-ICU and NDSS were administered by the same researcher.
      For demographic and preoperative risk factors of delirium, descriptive
      statistical analysis was performed. Concordance was assessed using kappa index.
      RESULTS: 106 patients were included, performing 214 evaluations. Incidence of
      delirium with the CAM-ICU scale was of 8.4%, and of 16.8% with NDSS. The
      concordance expressed by the index Kappa was of 0.541. CONCLUSIONS: The
      concordance between the CAM-ICU scale and the NDSS in the postoperative cardiac
      surgery and during the stay in the Intensive Care Unit is low. Currently, the use
      of the CAM-ICU was recommended in this context, but it must not be replaced for
      the NDSS.

PMID- 24910179
TI  - A strongly coupled graphene and FeNi double hydroxide hybrid as an excellent
      electrocatalyst for the oxygen evolution reaction.
AB  - Cost-effective electrocatalysts for the oxygen evolution reaction (OER) are
      critical to energy conversion and storage processes. A novel strategy is used to
      synthesize a non-noble-metal-based electrocatalyst of the OER by finely combining
      layered FeNi double hydroxide that is catalytically active and electric
      conducting graphene sheets, taking advantage of the electrostatic attraction
      between the two positively charged nanosheets. The synergy between the catalytic
      activity of the double hydroxide and the enhanced electron transport arising from
      the graphene resulted in superior electrocatalytic properties of the FeNi-GO
      hybrids for the OER with overpotentials as low as 0.21 V, which was further
      reduced to 0.195 V after the reduction treatment. Moreover, the turnover
      frequency at the overpotential of 0.3 V has reached 1 s(-1), which is much higher
      than those previously reported for non-noble-metal-based electrocatalysts.

PMID- 24910180
TI  - The effect of sulfur loading on the electrochemical performance of a sulfur
      polymer composite cathode coated on aluminium foil.
AB  - A scaling-up investigation of a sulfur-polymer cathode for rechargeable lithium
      sulfur batteries is reported. The proposed procedure uses a low cost aluminium
      current collector and is suitable for mass production of a composite cathode,
      with sulfur loading levels of up to 5.9 mg cm(-2), and good electrochemical
      performance. 

PMID- 24910181
TI  - Sediment PAH: contrasting levels in the Caspian Sea and Anzali Wetland.
AB  - A comparative study of 23 PAH congeners in sediment of the Caspian Sea coast and
      Anzali Wetland was conducted in 2010. Surface sediment was analyzed using
      chromatography and mass spectrometry. Total PAH concentrations ranged between 212
      and 9009 ng g(-1) dw. Spatial distribution maps revealed that PAH levels were
      higher in the coastal areas of the Caspian Sea where oil related activities have
      been common since 1800's. Diagnostic ratios analysis indicated that PAHs largely
      originated from petrogenic processes. PAH toxicity level was assessed using
      sediment quality guidelines and toxic equivalent concentrations to determine
      toxic effects on marine organism. Based on these investigations, in our study
      areas, the probability of toxicity for benthic organisms is "low to medium". The
      toxic equivalent concentrations of carcinogenic PAHs varied between 11 and 231 ng
      TEQ/g; higher total toxic equivalent concentrations values were found in the
      coastal areas of the Caspian Sea.

PMID- 24910182
TI  - A baseline study of metal contamination along the Namibian coastline for Perna
      perna and Choromytilus meridionalis.
AB  - The use of bivalves such as the brown mussel (Perna perna) and the black mussel
      (Choromytilus meridionalis) is common in the study of marine pollution and the
      effect of these pollutants on ecosystems and are important in both economic and
      ecological roles. Namibian marine ecosystems are threatened by pollution from
      mining, commercial fishing and population growth. The aims of this study were to
      determine baseline metal concentrations, spatial variation and variation between
      species. Metal levels in C. meridionalis from Guano Platform (GP) are the lowest
      of all the sites. The most polluted sites are Rocky Point (RP), Halifax Island
      (HIL) and between Walvis Bay and Swakopmund (WS). The bioaccumulation of metals
      between P. perna and C. meridionalis were not uniform for all metals. Overall the
      study indicates the condition of the coastline to be mostly normal, with Cd and
      Pb levels being of concern. 

PMID- 24910183
TI  - Sedimentary records of hydroxylated and methoxylated polybrominated diphenyl
      ethers in the southern Yellow Sea.
AB  - Although hydroxylated (OH-) and methoxylated (MeO-) polybrominated diphenyl
      ethers (PBDEs) have caused much concern in recent years, few reports had
      discussed on their input history. In this study, we measured the contents of nine
      MeO-BDEs, ten OH-BDEs, and total organic carbon (TOC) of two sediment cores from
      the southern Yellow Sea. 6-MeO-BDE-47, 2'-MeO-BDE-68, 6-OH-BDE-47, and 2'-OH-BDE
      68 were the predominant congeners in HH12, while only 2'-OH-BDE-68 and 6-OH-BDE
      47 were frequently detected in core HH11. The records showed that OH-/MeO-BDEs in
      both cores had increased rapidly since the 1950s. Their existence was detected at
      the bottom layers (~1800 s) prior to the production of PBDEs (1960s), thus OH
      /MeO-BDEs originate from natural origins rather than artificial PBDEs.
      Comparisons between TOC and OH-/MeO-BDEs indicated that TOC is a potential factor
      affecting the accumulation of OH-/MeO-BDEs in marine environments. Similar trends
      and significant correlations between OH-BDEs and MeO-BDEs suggest their common
      origins or interconversion.

PMID- 24910184
TI  - Biological neutralization and biosorption of dyes of alkaline textile industry
      wastewater.
AB  - The present work was aimed to secure biological neutralization and biosorption of
      dyes of an alkaline textile industrial effluent (ATIE) using an alkaliphilic
      bacterium, Enterococcus faecalis strain R-16 isolated from Gujarat coast. The
      isolate was capable and competent to bring down the pH of ATIE from 12.1 to 7.0
      within 2 h in the presence of carbon and nitrogen sources. Carboxylic group
      concentration (CGC), NMR and FT-IR analysis revealed production of carboxylic
      acid as a result of neutralization. The unconventional carbon and nitrogen
      sources like Madhuca indica flowers or sugar cane bagasse supported the growth of
      bacterium with effective neutralization and biosorption of dyes from ATIE. The
      process proved to be efficient, inexpensive and eco-friendly as compared to
      conventional chemical neutralization process.

PMID- 24910185
TI  - The invasive kelp Undaria pinnatifida (Laminariales, Ochrophyta) along the north
      coast of Portugal: distribution model versus field observations.
AB  - After the first report of Undaria pinnatifida in north Portugal (between 1999 and
      2007), a rapid spread of this species could be expected due to the presence of a
      stable population and the favourable environmental conditions proposed by
      distribution models. However, field surveys showed that U. pinnatifida was not
      present in most of the rocky shores in north Portugal. It seems that U.
      pinnatifida cannot outcompete native species outside of marinas in north
      Portugal. The only population in natural rocky shores was found in Buarcos, where
      this species was frequent. This study provides density data of U. pinnatifida
      that will be useful in the future to monitor changes on its abundance and
      distribution in the centre and south of Portugal. 

PMID- 24910186
TI  - Behavioural and biochemical stress responses of Palinurus elephas after exposure
      to boat noise pollution in tank.
AB  - This study examined the effects of boat noise on the behavioural and biochemical
      parameters of the Mediterranean spiny lobster (Palinurus elephas). The experiment
      was conducted in a tank equipped with a video and audio recording system. 18
      experimental trials, assigned to boat noise and control conditions, were
      performed using lobsters in single and group of 4 specimens. After a 1h
      habituation period, we audio- and video-recorded the lobsters for 1h. During the
      experimental phase, the animals assigned to the boat groups were exposed to boat
      noise pollution (a random sequence of boat noises). Exposure to the noise
      produced significant variations in locomotor behaviours and haemolymphatic
      parameters. Our results indicate that the lobsters exposed to boat noises
      increased significantly their locomotor activities and haemolymphatic
      bioindicator of stressful conditions such as glucose, total proteins, Hsp70
      expression and THC when tested both singly and in groups. 

PMID- 24910187
TI  - Transillumination-guided endoscopic endonasal dacryocystorhinostomy: approach to
      revision cases and challenging anatomy.
AB  - Dacryocystorhinostomy (DCR) is a surgical procedure in which a connection is
      established between the lacrimal sac and the nasal cavity in an effort to bypass
      an obstruction of the distal lacrimal apparatus. Endoscopic endonasal DCR (EEDCR)
      is a minimally invasive technique used to achieve this goal. In patients with
      altered anatomy, EEDCR can be challenging. Here, we describe the use of
      canalicular transillumination with EEDCR in three cases, and discuss the benefits
      of this technique. 

PMID- 24910188
TI  - miR-200 family in CRC primary tumors and metastases.

PMID- 24910189
TI  - Inhibition of cytochrome P450 by ethambutol in human liver microsomes.
AB  - Although cytochrome P450 inhibition is the major drug-drug interaction (DDI)
      mechanism in clinical pharmacotherapy, DDI of a number of well-established drugs
      have not been investigated. Rifampicin, isoniazid, pyrazinamide and ethambutol
      combination therapy inhibits clearance of theophylline in patients with
      tuberculosis. We determined the inhibitory effects of ethambutol on the
      activities of nine CYP isoforms including CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6,
      2E1 and 3A4 in pooled human liver microsomes (HLM). As measured by liquid
      chromatography-electrospray ionization tandem mass spectrometry, ethambutol
      exhibited strong inhibitory potential against CYP1A2 and CYP2E1, moderate against
      CYP2C19 and CYP2D6 and weak against CYP2A6, CYP2C9 and CYP3A4, based on the IC50
      values. The K(i) value of ethambutol for CYP1A2 was 1.4 MUM and for CYP2E1 was
      2.9 MUM. Inhibition of CYP1A2 and CYP2E1 was not increased by preincubation with
      ethambutol and beta-nicotinamideadenine dinucleotide phosphate (NADPH),
      suggesting that the ethambutol-induced CYP inhibition may not be metabolism
      dependent. Kinetic analysis showed that the inhibition of CYP1A2 and CYP2E1 by
      ethambutol was best fit to a competitive inhibition model. Formation of 1
      methylxanthene and 1,3-dimethyluric acid from theophylline in HLM was decreased
      to 47% and 36%, respectively, by 3.0 MUM ethambutol, which is comparable to its
      IC50 value against CYP1A2. Considering its maximal plasma concentrations of ~10
      MUM and long half-life of ~22 h, our findings raise the possibility that
      ethambutol causes significant DDIs in clinical situations with drugs with narrow
      therapeutic index, such as theophylline, in clinical situations.

PMID- 24910190
TI  - Role of oxidative stress-induced systemic and cavernosal molecular alterations in
      the progression of diabetic erectile dysfunction.
AB  - BACKGROUND: Erectile dysfunction (ED) is a prevalent complication of diabetes,
      and oxidative stress is an important feature of diabetic ED. Oxidative stress
      induced damage plays a pivotal role in the development of tissue alterations.
      However, the deleterious effects of oxidative stress in the corpus cavernosum
      with the progression of diabetes remain unclear. The aim of this study was to
      evaluate systemic and penile oxidative stress status in the early and late stages
      of diabetes. METHODS: Male Wistar streptozotocin-diabetic rats (and age-matched
      controls) were examined 2 (early) and 8 weeks (late) after the induction of
      diabetes. Systemic oxidative stress was evaluated by urinary H2 O2 and the ratio
      of circulating reduced/oxidized glutathione (GSH/GSSG). Penile oxidative status
      was assessed by H2 O2 production and 3-nitrotyrosine (3-NT) formation. Cavernosal
      endothelial nitric oxide synthase (eNOS) was analyzed by quantitative
      immunohistochemistry. Dual immunofluorescence was also performed for 3-NT and
      alpha-smooth muscle actin (alpha-SMA) and eNOS-alpha-SMA. RESULTS: There was a
      significant increase in urinary H2 O2 levels in both diabetic groups. The plasma
      GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal
      tissue, H2 O2 production was significantly increased in late diabetes. Reactivity
      for 3-NT was located predominantly in cavernosal smooth muscle (SM) and was
      significantly reduced in late diabetes. Quantitative immunohistochemistry
      revealed a significant decrease in eNOS levels in cavernosal SM and endothelium
      in late diabetes. CONCLUSIONS: The findings indicate that the noxious effects of
      oxidative stress are more prominent in late diabetes. Increased penile protein
      oxidative modifications and decreased eNOS expression may be responsible for
      structural and/or functional deregulation, contributing to the progression of
      diabetes-associated ED.

PMID- 24910191
TI  - Real time Raman imaging to understand dissolution performance of amorphous solid
      dispersions.
AB  - We have employed for the first time Raman spectroscopic imaging along with multi
      variate curve resolution (MCR) analysis to investigate in real time and in-situ
      the dissolution mechanisms that underpin amorphous solid dispersions, with data
      being collected directly from the dosage form itself. We have also employed a
      novel rotating disk dissolution rate (RDDR) methodology to track, through the use
      of high-performance liquid chromatography (HPLC), the dissolution trends of both
      drug and polymer simultaneously in multi-component systems. Two formulations of
      poorly water-soluble felodipine in a polymeric matrix of copovidone VA64 which
      have different drug loadings of 5% and 50% w/w were used as models with the aim
      of studying the effects of increasing the amount of active ingredient on the
      dissolution performance. It was found that felodipine and copovidone in the 5%
      dispersion dissolve with the same dissolution rate and that no Raman spectral
      changes accompanied the dissolution, indicating that the two components dissolve
      as single entity, whose behaviour is dominated by water-soluble copovidone. For
      the 50% drug-loaded dispersion, partial RDDR values of both felodipine and
      copovidone were found to be extremely low. MCR Raman maps along with classical
      Raman/X-ray powder diffraction (XRPD) characterisation revealed that after an
      initial loss of copovidone from the extrudate the drug re-crystallises, pointing
      to a release dynamics dependent on the low water solubility and high
      hydrophobicity of felodipine. Raman imaging revealed different rates of
      transition from amorphous to crystalline felodipine at different locations within
      the dosage form. 

PMID- 24910192
TI  - Controlling molecular transport and sustained drug release in lipid-based liquid
      crystalline mesophases.
AB  - Lipid-based lyotropic liquid crystals, also referred to as reversed liquid
      crystalline mesophases, such as bicontinuous cubic, hexagonal or micellar cubic
      phases, have attracted deep interest in the last few decades due to the
      possibility of observing these systems at thermodynamic equilibrium in excess
      water conditions. This becomes of immediate significance for applications in the
      colloidal environment, such as in the food, cosmetic and pharmaceutical arenas.
      One possible application regarded as very promising is that of controlled
      delivery of functional ingredients. Different crystallographic structures of the
      lipid mesophase give access to different diffusion coefficients and distinct
      diffusion modes. It becomes thus crucial to engineer the space group of the
      mesophase in a controlled way, and ideally, in a stimuli-responsive manner. In
      this article we review the state of the art on diffusion and molecular transport
      in lipid-based mesophases and we discuss recent contributions to the controlled
      delivery of molecules and colloids through these systems. In particular we focus
      on the different available strategies relying on either endogenous or exogenous
      stimuli to induce changes in the symmetry and transport properties of lipid-based
      mesophases and we discuss the impact and implications this may have on controlled
      drug delivery. 

PMID- 24910194
TI  - Lectin-decorated nanoparticles enhance binding to the inflamed tissue in
      experimental colitis.
AB  - A major limitation in the drug treatment of inflammatory bowel disease is the
      inability to deliver the drug selectively towards the inflamed tissues.
      Nanotechnology-based drug delivery systems have led to an amelioration of the
      therapeutic selectivity but still the majority of the entrapped drug is
      eliminated without exercising a therapeutic effect. Here, lectin-decorated drug
      loaded nanoparticles (NP) are suggested for active targeting and selective
      adhesion to the inflamed tissue in experimental colitis. Peanut (PNA) and wheat
      germ (WGA) lectins were covalently bound to the surface of NP and were tested for
      their stability and degree of bioadhesion in cell culture. In-vivo, the
      selectivity of bioadhesion and distribution of NP throughout the intestinal tract
      as well as the therapeutic benefit for glucocorticoid loaded lectin-NP was
      studied in murine colitis models. Quantitative adhesion analyses showed that
      lectin-conjugated NP exhibited a much higher binding and selectivity to inflamed
      tissue compared to plain NP (PNA conjugates: 52.2+/-5.6%; WGA conjugates: 22.0+/
      0.8%; plain NP: 18.6+/-9.8%). Lectin-associated NP revealed a further increase in
      the selectivity of bioadhesion towards inflamed tissues which partially
      translates into increased therapeutic efficiency. In terms of therapeutic
      efficiency, all glucocorticoid containing formulations revealed an enhanced
      therapeutic effect with lectin conjugates especially PNA-NP (myeloperoxidase:
      55+/-37U/g; TNF-alpha: 3880+/-380U/g) compared to plain NP (myeloperoxidase:
      145+/-98U/g; TNF-alpha: 6971+/-1157U/g). Targeted NP by using lectins, especially
      with PNA, as stable targeting moiety in the gastrointestinal tract appears to be
      a very promising tool in future treatment of inflammatory bowel disease. 

PMID- 24910193
TI  - Silk-based biomaterials for sustained drug delivery.
AB  - Silk presents a rare combination of desirable properties for sustained drug
      delivery, including aqueous-based purification and processing options without
      chemical cross-linkers, compatibility with common sterilization methods,
      controllable and surface-mediated biodegradation into non-inflammatory by
      products, biocompatibility, utility in drug stabilization, and robust mechanical
      properties. A versatile silk-based toolkit is currently available for sustained
      drug delivery formulations of small molecule through macromolecular drugs, with a
      promise to mitigate several drawbacks associated with other degradable sustained
      delivery technologies in the market. Silk-based formulations utilize silk's well
      defined nano- through microscale structural hierarchy, stimuli-responsive self
      assembly pathways and crystal polymorphism, as well as sequence and genetic
      modification options towards targeted pharmaceutical outcomes. Furthermore, by
      manipulating the interactions between silk and drug molecules, near-zero order
      sustained release may be achieved through diffusion- and degradation-based
      release mechanisms. Because of these desirable properties, there has been
      increasing industrial interest in silk-based drug delivery systems currently at
      various stages of the developmental pipeline from pre-clinical to FDA-approved
      products. Here, we discuss the unique aspects of silk technology as a sustained
      drug delivery platform and highlight the current state of the art in silk-based
      drug delivery. We also offer a potential early development pathway for silk-based
      sustained delivery products. 

PMID- 24910196
TI  - Hypertriglyceridaemic waist phenotype as a simple predictive marker of incident
      diabetes in Asian-Indian men with prediabetes.
AB  - AIM: To determine prospectively the association of baseline hypertriglyceridaemic
      waist phenotype with incident diabetes in Asian-Indian men with impaired glucose
      tolerance. METHODS: In a randomized 2-year diabetes prevention trial in 517 men
      with impaired glucose tolerance, 123 (23.8%) developed diabetes. Baseline
      anthropometric, metabolic and clinical variables were estimated. Associations of
      hypertriglyceridaemic waist phenotype (waist circumference >= 90cm and a serum
      triglyceride level of >= 1.7 mmol/l) with insulin resistance and incident
      diabetes were assessed using multiple linear regression and Cox's proportional
      hazard models, respectively. RESULTS: Men with an isolated enlarged waistline and
      hypertriglyceridaemic waist phenotype had significantly higher BMI and percentage
      of total body fat compared with the group with normal waistline and triglyceride
      levels and the group with isolated hypertriglyceridaemia. The men with
      hypertriglyceridaemic waist phenotype had higher insulin resistance (mean +/- sd
      homeostasis model assessment of insulin resistance value: 3.6 +/- 1.5) compared
      with those in the isolated enlarged waistline, the isolated hypertriglyceridaemia
      or the normal waistline and triglyceride level groups (3.1 +/- 1.4, 2.7 +/- 1.0
      and 2.5 +/- 1.1, respectively, all P < 0.05 compared with hypertriglyceridaemic
      waist phenotype). Multiple linear regression analyses showed that
      hypertriglyceridaemic waist phenotype was significantly associated with insulin
      resistance after adjusting for age, BMI, family history, percentage of total body
      fat, smoking, alcohol intake, 2-h plasma glucose and HDL cholesterol level.
      Hypertriglyceridaemic waist phenotype was independently associated with incident
      diabetes after adjusting for the above confounders and gamma-glutamyl transferase
      (hazard ratio 1.49, 95% CI 1.01-2.21; P = 0.047). The association of
      hypertriglyceridaemic waist phenotype with incident diabetes was abolished when
      insulin resistance was introduced into the model (hazard ratio 1.39, 95% CI 0.092
      2.10; P=0.12). CONCLUSIONS: Hypertriglyceridaemic waist phenotype is a simple
      clinical proxy measurement for insulin resistance and is strongly associated with
      incident diabetes in Asian-Indian men with impaired glucose tolerance.

PMID- 24910197
TI  - The structural elucidation and antimicrobial activities of two new monoterpene
      glucoside derivatives from Lomatogonium carinthiacum (Wulf) Reichb.

PMID- 24910195
TI  - Components of cancer metabolism and therapeutic interventions.
AB  - All forms of life share a common indispensible need of energy. The requirement of
      energy is necessary for an organism not only to survive but also to thrive. The
      metabolic activities in normal cells rely predominately on mitochondrial
      oxidative phophorylation for energy generation in the form of ATP. On the
      contrary, cancer cells predominately rely on glycolysis rather than oxidative
      phosphorylation. It is long believed that an impairment of mitochondrial
      oxidative phosphorylation is the cause of this glycolytic phenotype observed in
      cancers. However, studies in cancer metabolism have revealed that mitochondrial
      function in many cancers is intact. It has also been observed that cancers
      utilize various forms of metabolism. The various metabolic phenotypes that are
      employed by cancer cells have a common purpose, to balance macromolecular
      biosynthesis and sufficient ATP production in order to support the rapid
      proliferation rate characteristic of these aberrant cells. These metabolic
      pathways are attractive targets for possible therapeutic interventions and
      currently research is underway to meet this end. More importantly, normal cells
      have essentially the same metabolic requirements as cancer cells so finding an
      approach to target these metabolic pathways without incurring detrimental effects
      on normal tissues remains the challenge. 

PMID- 24910198
TI  - Structure of RPA32 bound to the N-terminus of SMARCAL1 redefines the binding
      interface between RPA32 and its interacting proteins.
AB  - Replication protein A subunit RPA32 contains a C-terminal domain that interacts
      with a variety of DNA damage response proteins including SMARCAL1, Tipin, UNG2
      and XPA. We have solved the high-resolution crystal structure of RPA32 C-terminal
      domain (RPA32C) in complex with a 26-amino-acid peptide derived from the N
      terminus of SMARCAL1 (SMARCAL1N). The RPA32C-SMARCAL1N structure reveals a 1 : 1
      binding stoichiometry and displays a well-ordered binding interface. SMARCAL1N
      adopts a long alpha-helical conformation with the highly conserved 11 residues
      aligned on one face of the alpha-helix showing extensive interactions with the
      RPA32C domain. Extensive mutagenesis experiments were performed to corroborate
      the interactions observed in crystal structure. Moreover, the alpha1/alpha2 loop
      of the RPA32C domain undergoes a conformational rearrangement upon SMARCAL1N
      binding. NMR study has further confirmed that the RPA32C-SMARCAL1N interaction
      induces conformational changes in RPA32C. Isothermal titration calorimetry
      studies have also demonstrated that the conserved alpha-helical motif defined in
      the current study is required for sufficient binding of RPA32C. Taken together,
      our study has provided convincing structural information that redefines the
      common recognition pattern shared by RPA32C interacting proteins. DATABASE: The
      atomic coordinates of RPA32C in complex with 26-aa SMARCAL1 (SMARCAL1N) peptide
      have been deposited at the Protein Data Bank with accession code 4MQV. STRUCTURED
      DIGITAL ABSTRACT: RPA32 and SMARCAL1 bind by isothermal titration calorimetry(1,
      2, 3, 4, 5, 6, 7, 8, 9) RPA32 and SMARCAL1 bind by molecular sieving (View
      interaction) RPA32 and SMARCAL1 bind by x-ray crystallography (View interaction)
      Tipin and RPA32 bind by isothermal titration calorimetry (1, 2) RPA32 and UNG2
      bind by isothermal titration calorimetry (1, 2, 3) SMARCAL1 and RPA32 bind by
      nuclear magnetic resonance (View interaction) UNG2 and RPA32 bind by nuclear
      magnetic resonance (View interaction) Tipin and RPA32 bind by nuclear magnetic
      resonance (View interaction).

PMID- 24910199
TI  - High-intensity exercise causes greater irisin response compared with low
      intensity exercise under similar energy consumption.
AB  - Irisin is mainly released from skeletal muscle (myocytes) and promotes
      thermogenesis by browning of the white adipose tissue. Although exercise has been
      shown to increase irisin concentration in blood and myocytes via up-regulation
      peroxisome proliferator receptor gamma coactivator-1alpha (PGC-1alpha)
      expression, the influence of exercise intensity on irisin secretion remains
      unclear. Therefore, we determined circulating irisin responses following a single
      bout of running at different intensities. Six sedentary males underwent treadmill
      running under two different conditions: a low-intensity (40% of VO2max) exercise
      trial (LIE) or a high-intensity (80% of VO2max) exercise trial (HIE). The
      exercises in LIE and HIE were lasted for 20 and 40 min, respectively. All
      subjects underwent the two trials on separate days, and a randomized cross-over
      design was used. Blood samples were collected before (Pre) and immediately after
      exercise, at 3, 6, and 19 h after exercise. Energy consumption during exercise
      did not significantly differ between the two trials. HIE significantly increased
      blood lactate and serum lactate dehydrogenase levels (P < 0.05). Compared with
      pre-exercise levels, the irisin concentrations were elevated at 6 h (18%
      increase) and 19 h (23% increase) after HIE, but significantly decreased after
      LIE. The relative irisin concentrations (compared with pre-exercise levels) were
      significantly greater in HIE than in LIE immediately after exercise, and at 6 and
      19 h after exercise (P < 0.05). These findings suggest that irisin secretion
      after acute running exercise is affected by exercise intensity, independent of
      energy consumption. 

PMID- 24910200
TI  - The A>T polymorphism of the tribbles homolog 1 gene is associated with serum
      triglyceride concentrations in Japanese community-dwelling women.
AB  - Recent genome-wide association studies have identified Tribbles homolog 1 (TRIB1)
      as one of the candidate genes associated with lipid profiles. TRIB1 is known to
      interact with MAP kinases, thereby regulating their activities. The single
      nucleotide polymorphism rs2954029 of TRIB1 is located within an intron and is
      associated with lipid profiles. The aim of the present study is to investigate
      the TRIB1 rs2954029 (A>T polymorphism) with conventional predictors of coronary
      artery diseases such as carotid intima-media thickness (CIMT) and cardio-ankle
      vascular index (CAVI), and with lipid profiles in general population. This study
      enrolled 2,581 Japanese adults, 942 men and 1,639 women with a median age of 68
      years (range 29 to 94 years), who participated in a screening program for the
      general population living in Goto City, Nagasaki Prefecture, Japan from 2008 to
      2010. For the determination of TRIB1 rs2954029 genotypes, the polymerase chain
      reaction method was used. The differences in each parameter among the TRIB1
      rs2954029 genotypes were evaluated using analysis of covariance. Genotype
      frequencies of TRIB1 rs2954029 in all participants were 25.5% for AA, 50.4% for
      AT, and 24.0% for TT. In women, the AA genotype showed significantly higher log
      triglyceride (TG) concentrations than the AT genotype (P = 0.004) and the AT + TT
      genotypes (P = 0.004). On the other hand, there were no associations with CIMT
      and CAVI among the TRIB1 rs2954029 genotypes. In conclusion, the TRIB1 rs2954029
      is associated with serum TG concentrations in Japanese community-dwelling women. 

PMID- 24910201
TI  - TrkB kinase activity is critical for recovery of respiratory function after
      cervical spinal cord hemisection.
AB  - Neuroplasticity following spinal cord injury contributes to spontaneous recovery
      over time. Recent studies highlight the important role of brain-derived
      neurotrophic factor (BDNF) signaling via the high-affinity tropomyosin-related
      kinase (Trk) receptor subtype B (TrkB) in recovery of rhythmic diaphragm activity
      following unilateral spinal hemisection at C2 (C2SH). We hypothesized that TrkB
      kinase activity is necessary for spontaneous recovery of diaphragm activity post
      C2SH. A chemical-genetic approach employing adult male TrkB(F616A) mice (n=49)
      was used to determine the impact of inhibiting TrkB kinase activity by the
      phosphoprotein phosphatase 1 inhibitor derivative 1NMPP1 on recovery of
      ipsilateral hemidiaphragm EMG activity. In mice, C2SH was localized primarily to
      white matter tracts comprising the lateral funiculus. The extent of damaged
      spinal cord (~27%) was similar regardless of the presence of functional recovery,
      consistent with spontaneous recovery reflecting neuroplasticity primarily of
      contralateral spared descending pathways to the phrenic motor pools. Ipsilateral
      hemidiaphragm EMG activity was verified as absent in all mice at 3days post-C2SH.
      By 2weeks after C2SH, ipsilateral hemidiaphragm EMG activity was present in 39%
      of vehicle-treated mice compared to 7% of 1NMPP1-treated mice (P=0.03). These
      data support the hypothesis that BDNF/TrkB signaling involving TrkB kinase
      activity plays a critical role in spontaneous recovery of diaphragm activity
      following cervical spinal cord injury. 

PMID- 24910202
TI  - Peripheral prostaglandin E2 prolongs the sensitization of nociceptive dorsal root
      ganglion neurons possibly by facilitating the synthesis and anterograde axonal
      trafficking of EP4 receptors.
AB  - Prostaglandin E2 (PGE2), a well-known pain mediator enriched in inflamed tissues,
      plays a pivotal role in the genesis of chronic pain conditions such as
      inflammatory and neuropathic pain. PGE2-prolonged sensitization of nociceptive
      dorsal root ganglion (DRG) neurons (nociceptors) may contribute to the transition
      from acute to chronic pain. However, the underlying cellular mechanisms are
      poorly understood. In this study, we tested the hypothesis that facilitating
      synthesis and anterograde axonal trafficking of EP receptors contribute to PGE2
      prolonged nociceptor sensitization. Intraplantar (i.pl.) injection of a
      stabilized PGE2 analog, 16,16 dimethyl PGE2 (dmPGE2), in a dose- and time
      dependent manner, not only elicited primary tactile allodynia which lasted for
      1d, but also prolonged tactile allodynia evoked by a subsequent i.pl. injection
      of dmPGE2 from 1d to 4d. Moreover, the duration of tactile allodynia was
      progressively prolonged following multiple sequential i.pl. injections of dmPGE2.
      Co-injection of the selective EP1 or EP4 receptor antagonist, the inhibitors of
      cAMP, PKA, PKC, PKCepsilon or PLC as well as an interleukin-6 (IL-6) neutralizing
      antiserum differentially blocked primary tactile allodynia elicited by the 1st
      dmPGE2 and the prolonged tactile allodynia evoked by the 2nd dmPGE2, suggesting
      the involvement of these signaling events in dmPGE2-induced nociceptor activation
      and sensitization. Co-injection of a selective COX2 inhibitor or two EP4
      antagonists prevented or shortened inflammagen-prolonged nociceptor
      sensitization. I.pl. injection of dmPGE2 or carrageenan time-dependently
      increased EP4 levels in L4-6 DRG neurons and peripheral nerves. EP4 was expressed
      in almost half of IB4-binding nociceptors of L4-6 DRG. Taken together, our data
      suggest that stimulating the synthesis and anterograde axonal trafficking to
      increase EP4 availability at the axonal terminals of nociceptors is likely a
      novel mechanism underlying PGE2-prolonged nociceptor sensitization. Blocking
      COX2/PGE2/EP4 signaling at an earlier stage of inflammation or injury is crucial
      for preventing the transition from acute pain to a chronic state. 

PMID- 24910203
TI  - Impact of glucagon-like peptide-1 on myocardial glucose metabolism revisited.
AB  - The gut hormone glucagon-like peptide-1 (GLP-1) is an insulinotropic incretin
      with significant cardiovascular impact. Two classes of medication, GLP-1
      analogues and DPP-4 inhibitors, have been developed that circumvent the rapid
      degradation of GLP-1 by the enzyme dipeptidyl peptidase-4 (DPP-4), both enhance
      the incretin effect and were developed for the treatment of type 2 diabetes.
      Several mechanisms suggesting that DPP-4 inhibitors, GLP-1, and analogues could
      have a protective effect on the cardiovascular risk profile have been forwarded;
      e.g., reductions of blood glucose, body weight, blood pressure, improvement in
      left ventricular ejection fraction, myocardial perfusion, atherosclerosis
      development, and endothelial function. Despite this, the reasons for a decreased
      risk of developing cardiovascular disease and reduced post-ischaemia damage are
      still poorly understood. The potentially beneficial effect of GLP-1 stimulation
      may rely on, among others, improved myocardial glucose metabolism. This review
      focuses on the dogma that GLP-1 receptor stimulation may provide beneficial
      cardiovascular effects, possibly due to enhanced myocardial energetic efficiency,
      by increasing myocardial glucose uptake. The published literature was
      systematically reviewed and the applied models evaluated since the outcomes of
      varying studies differ substantially. Reports on the effect of GLP-1R stimulation
      on myocardial metabolism are conflicting and should be evaluated carefully. There
      is limited and conflicting information on the impact of these agents in real life
      patients and while clinical outcome studies investigating the cardiovascular
      effects of GLP-1 based therapies have been initiated, the first two studies, both
      on DPP-4 inhibitors, designed specifically to evaluate cardiac safety reported
      largely neutral outcomes. 

PMID- 24910204
TI  - PCDH20 functions as a tumour-suppressor gene through antagonizing the Wnt/beta
      catenin signalling pathway in hepatocellular carcinoma.
AB  - Several members of protocadherins have been found involved in human
      carcinogenesis, but little is known about PCDH20 in HCC. Here in this study,
      using quantitative real-time RT-PCR assay, we demonstrated the downregulation of
      PCDH20 expression in 6 of 7 HCC cell lines tested. Similarly, PCDH20 expression
      in primary HCC tissues was also significantly downregulated in comparison with
      that in either disease-free normal liver tissues or the adjacent nontumour liver
      tissues (P < 0.001, respectively). Among HCC tumour tissues studied, about 48%
      (51/107) of them showed reduced PCDH20 mRNA level. Further statistic analysis
      revealed that the reduced PCDH20 mRNA level in tumour tissues was much more
      common in younger patients group (aged <50 years) than that in older group (>=50
      years) (60% vs 33%, P = 0.0303). Loss of heterozygosity (LOH) and promoter
      hypermethylation analysis revealed that deletion and/or aberrant epigenetic
      modulation of PCDH20 gene account for its downregulation, at least in a fraction
      of tumour specimens. Moreover, ectopic expression of PCDH20 in HCC cells
      significantly suppressed cell proliferation, clonogenicity, migration and tumour
      formation. Notably, we proved for the first time that, via activating GSK-3beta,
      PCDH20 could inhibit Wnt/beta-catenin signalling pathway. Furthermore, our data
      suggest that PCDH20 may conduct its Wnt/beta-catenin signalling antagonizing
      function through suppressing Akt and Erk activities and promoting GSK-3beta
      signalling activities. However, the detailed mechanism remained undiscovered. In
      conclusion, our data here strongly suggested that PCDH20 may act as a candidate
      tumour suppressor in HCC.

PMID- 24910205
TI  - Modeling chlorophyll a fluorescence transient: relation to photosynthesis.
AB  - To honor Academician Alexander Abramovitch Krasnovsky, we present here an
      educational review on the relation of chlorophyll a fluorescence transient to
      various processes in photosynthesis. The initial event in oxygenic photosynthesis
      is light absorption by chlorophylls (Chls), carotenoids, and, in some cases,
      phycobilins; these pigments form the antenna. Most of the energy is transferred
      to reaction centers where it is used for charge separation. The small part of
      energy that is not used in photochemistry is dissipated as heat or re-emitted as
      fluorescence. When a photosynthetic sample is transferred from dark to light, Chl
      a fluorescence (ChlF) intensity shows characteristic changes in time called
      fluorescence transient, the OJIPSMT transient, where O (the origin) is for the
      first measured minimum fluorescence level; J and I for intermediate inflections;
      P for peak; S for semi-steady state level; M for maximum; and T for terminal
      steady state level. This transient is a real signature of photosynthesis, since
      diverse events can be related to it, such as: changes in redox states of
      components of the linear electron transport flow, involvement of alternative
      electron routes, the build-up of a transmembrane pH gradient and membrane
      potential, activation of different nonphotochemical quenching processes,
      activation of the Calvin-Benson cycle, and other processes. In this review, we
      present our views on how different segments of the OJIPSMT transient are
      influenced by various photosynthetic processes, and discuss a number of studies
      involving mathematical modeling and simulation of the ChlF transient. A special
      emphasis is given to the slower PSMT phase, for which many studies have been
      recently published, but they are less known than on the faster OJIP phase.

PMID- 24910206
TI  - Nano-sized manganese-calcium cluster in photosystem II.
AB  - Cyanobacteria, algae, and plants are the manufacturers that release O2 via water
      oxidation during photosynthesis. Since fossil resources are running out,
      researchers are now actively trying to use the natural catalytic center of water
      oxidation found in the photosystem II (PS II) reaction center of oxygenic
      photosynthetic organisms to synthesize a biomimetic supercatalyst for water
      oxidation. Success in this area of research will transcend the current bottleneck
      for the development of energy-conversion schemes based on sunlight. In this
      review, we go over the structure and function of the water-oxidizing complex
      (WOC) found in Nature by focusing on the recent advances made by the
      international research community dedicated to achieve the goal of artificial
      water splitting based on the WOC of PS II. 

PMID- 24910207
TI  - Mechanisms of phototransformation of protochlorophyllide into chlorophyllide.
AB  - The purpose of this review is to summarize and discuss data obtained in studies
      on the mechanisms of the primary photophysical and photochemical reactions of
      protochlorophyllide photoreduction in plant materials (etiolated leaves and leaf
      homogenates) and in model systems. Based on the results of numerous studies, it
      can be stated that the reduction of active forms of the chlorophyll precursor is
      a multistep process comprising two or three short-lived intermediates
      characterized by a singlet ESR signal. The first intermediate is probably a
      complex with charge transfer between protochlorophyllide and the hydride ion
      donor NADPH. The conserved tyrosine residue Tyr193 of protochlorophyllide
      oxidoreductase is the donor of the second proton. 

PMID- 24910208
TI  - Spectral and kinetic parameters of phosphorescence of triplet chlorophyll a in
      the photosynthetic apparatus of plants.
AB  - Spectral and kinetic parameters and quantum yield of IR phosphorescence
      accompanying radiative deactivation of the chlorophyll a (Chl a) triplet state
      were compared in pigment solutions, greening and mature plant leaves, isolated
      chloroplasts, and thalluses of macrophytic marine algae. On the early stages of
      greening just after the Shibata shift, phosphorescence is determined by the bulk
      Chl a molecules. According to phosphorescence measurement, the quantum yield of
      triplet state formation is not less than 25%. Further greening leads to a strong
      decrease in the phosphorescence yield. In mature leaves developing under normal
      irradiation conditions, the phosphorescence yield declined 1000-fold. This
      parameter is stable in leaves of different plant species. Three spectral forms of
      phosphorescence-emitting chlorophyll were revealed in the mature photosynthetic
      apparatus with the main emission maxima at 955, 975, and 995 nm and lifetimes
      ~1.9, ~1.5, and 1.1-1.3 ms. In the excitation spectra of chlorophyll
      phosphorescence measured in thalluses of macrophytic green and red algae, the
      absorption bands of Chl a and accessory pigments - carotenoids, Chl b, and
      phycobilins - were observed. These data suggest that phosphorescence is emitted
      by triplet chlorophyll molecules that are not quenched by carotenoids and
      correspond to short wavelength forms of Chl a coupled to the normal light
      harvesting pigment complex. The concentration of the phosphorescence-emitting
      chlorophyll molecules in chloroplasts and the contribution of these molecules to
      chlorophyll fluorescence were estimated. Spectral and kinetic parameters of the
      phosphorescence corresponding to the long wavelength fluorescence band at 737 nm
      were evaluated. The data indicate that phosphorescence provides unique
      information on the photophysics of pigment molecules, molecular organization of
      the photosynthetic apparatus, and mechanisms and efficiency of photodynamic
      stress in plants.

PMID- 24910209
TI  - Oxylipins and plant abiotic stress resistance.
AB  - Oxylipins are signaling molecules formed enzymatically or spontaneously from
      unsaturated fatty acids in all aerobic organisms. Oxylipins regulate growth,
      development, and responses to environmental stimuli of organisms. The oxylipin
      biosynthesis pathway in plants includes a few parallel branches named after first
      enzyme of the corresponding branch as allene oxide synthase, hydroperoxide lyase,
      divinyl ether synthase, peroxygenase, epoxy alcohol synthase, and others in which
      various biologically active metabolites are produced. Oxylipins can be formed non
      enzymatically as a result of oxygenation of fatty acids by free radicals and
      reactive oxygen species. Spontaneously formed oxylipins are called
      phytoprostanes. The role of oxylipins in biotic stress responses has been
      described in many published works. The role of oxylipins in plant adaptation to
      abiotic stress conditions is less studied; there is also obvious lack of
      available data compilation and analysis in this area of research. In this work we
      analyze data on oxylipins functions in plant adaptation to abiotic stress
      conditions, such as wounding, suboptimal light and temperature, dehydration and
      osmotic stress, and effects of ozone and heavy metals. Modern research articles
      elucidating the molecular mechanisms of oxylipins action by the methods of
      biochemistry, molecular biology, and genetics are reviewed here. Data on the role
      of oxylipins in stress signal transduction, stress-inducible gene expression
      regulation, and interaction of these metabolites with other signal transduction
      pathways in cells are described. In this review the general oxylipin-mediated
      mechanisms that help plants to adjust to a broad spectrum of stress factors are
      considered, followed by analysis of more specific responses regulated by
      oxylipins only under certain stress conditions. New approaches to improvement of
      plant resistance to abiotic stresses based on the induction of oxylipin-mediated
      processes are discussed. 

PMID- 24910210
TI  - New inhibitors of 5-lipoxygenase catalytic activity based on 2-(3
      methylphenyl)propanoic acid and 4-substituted morpholine derivatives.
AB  - New potential inhibitors of 5-lipoxygenase (5-LOX) based on the structure of 2-(3
      benzoylphenyl)propanoic acid (an active component of the nonsteroidal
      antiinflammatory drug Ketoprofen) were designed using the SARD-21 program. The
      docking of these compounds in the active site of 5-LOX suggested that seven
      compounds can interact with this enzyme. Two of them can also be dual inhibitors
      of 5-LOX and two isoforms of cyclooxygenase. 

PMID- 24910211
TI  - Functional modification of fibronectin by N-terminal FXIIIa-mediated
      transamidation.
AB  - A straightforward strategy is presented for the site-specific incorporation of
      fluorophores or reactive probes into the extracellular matrix (ECM) protein
      fibronectin (Fn) by using the enzyme-catalyzed transamidation by activated factor
      XIII. Characterization by SDS-PAGE, western blotting, absorption measurements,
      mass spectrometry, and stepwise photobleaching for labeling quantification at the
      single-molecule level showed that the labeling was efficient and restricted to
      the N-terminal tails. The introduction of labels did not interfere with Fn
      fibrillogenesis, as verified by the incorporation of fluorescently labeled Fn
      into ECM and manually pulled Fn fibers. Site-specific incorporation of an azide
      was used to create a template for bioorthogonal click chemistry reactions in a
      second bioconjugation step, thus offering versatile modification and application
      possibilities in the context of matrix biology and tissue engineering. 

PMID- 24910212
TI  - Mapping algorithms from QLQ-C30 to EQ-5D utilities: no firm ground to stand on
      yet.
AB  - AIM: Over the last years several mapping or cross-walking algorithms for deriving
      utilities from QLQ-C30 scores have been published. However their external
      predictive accuracy has not yet been systematically compared. METHODS: We tested
      the external validity of previously published mapping algorithms to transform the
      European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire
      responses to EQ-5D derived Utilities. RESULTS: When applied to different data
      sets, the currently published mapping showed a large variation between algorithms
      of the values of the mapped utilities, a low accuracy of the mapping compared to
      the observed EQ-5D utilities and no consistent performance between competing
      algorithms. DISCUSSION: Therefore direct mapping from QLQ-C30 profiles to EQ-5D
      utilities using published algorithms should be viewed cautiously.

PMID- 24910213
TI  - In vivo evaluation of bone deposition in macroporous titanium implants loaded
      with mesenchymal stem cells and strontium-enriched hydrogel.
AB  - Bone-implant integration represents a major requirement to grant implant
      stability and reduce the risk of implant loosening. This study investigates the
      effect of progenitor cells and strontium-enriched hydrogel on the
      osseointegration of titanium implants. To mimic implant-bone interaction, an
      ectopic model was developed grafting Trabecular Titanium(TM) (TT) implants into
      decellularized bone seeded with human bone marrow mesenchymal stem cells
      (hBMSCs). TT was loaded or not with strontium-enriched amidated
      carboxymethylcellulose (CMCA) hydrogel and/or hBMSCs. Constructs were implanted
      subcutaneously in athymic mice and osteodeposition was investigated with
      microcomputed tomography (micro-CT), scanning electron microscopy (SEM), and pull
      out test at 4, 8, and 12 weeks. Fluorescence imaging was performed at 8 and 12
      weeks, histology at 4 and 8 weeks. Micro-CT demonstrated the homogeneity of the
      engineered bone in all groups, supporting the reproducibility of the ectopic
      model. Fluorescence imaging, histology, SEM and pull-out mechanical testing
      showed superior tissue ingrowth in TT implants loaded with both strontium
      enriched CMCA and hBMSCs. In our model, the synergic action of the bioactive
      hydrogel and hBMSCs increased both the bone deposition and TT integration. Thus,
      we suggest that using orthopedic prosthetic implant preloaded with strontium
      enriched CMCA and seeded with BMSCs could represent a valid single-step surgical
      strategy to improve implant osseointegration.

PMID- 24910214
TI  - A prospective study concerning the relationship between metal allergy and post
      operative pain following total hip and knee arthroplasty.
AB  - PURPOSE: A prospective study was conducted to detect whether a relationship
      exists between metal allergy and post-operative pain in total hip and knee
      arthroplasty patients. We postulated that to some extent a relationship does
      exist between them. MATERIALS AND METHODS: Patients who had undergone total hip
      and knee arthroplasty surgery because of hip and knee disease were included. The
      exclusion criteria were patients who were treated with immunosuppressor two weeks
      pre-operatively, skin conditions around the patch testing site, and other
      uncontrollable factors. Each patient agreed to patch testing for three days
      before surgery. Photographic images before patch testing, two and three days
      after patch testing were obtained to evaluate the final incidence of metal
      allergy. The patch tests contained 12 metal elements; chromium, cobalt, nickel,
      molybdenum, titanium, aluminium, vanadium, iron, manganese, tin, zirconium, and
      copper. Two independent observers evaluated the images. The results were divided
      into a non-metal allergy group and a metal allergy group. Pre-operative and
      postoperative VAS score, lymphocyte transforming test, and X-rays were collected
      to detect the relationship between metal allergy and post-operative pain
      following total hip and knee arthroplasty. RESULTS: There were 96 patients who
      underwent pre-operative patch testing. The overall metal allergy rate was 51.1%
      (49/96) in our study. Nickel, cobalt, manganese, and tin were the most common
      allergic metal elements in our study. Nine inappropriate cases were excluded, and
      87 patients were finally included in our study. There were 36 metal allergy and
      26 non-metal allergy patients in the THA group, while 11 metal allergy and 14 non
      metal allergy patients were found in the TKA group. We found no relationship
      existed between metal allergy and post-surgery pain in total hip and knee
      arthroplasty. CONCLUSION: Pain caused by metal allergy usually presents as
      persistent and recurrent pain. The white cell count, C-reactive protein,
      erythrocyte sedimentation rate and postoperative radiographs were not affected.
      Currently, patch testing and lymphocyte transforming tests are used for metal
      allergy diagnosis. We deemed that a relationship between post-surgery pain and
      metal allergy in total hip and knee patients may exist to some extent. Larger
      samples and longer follow-up time are essential for further study.

PMID- 24910215
TI  - Intramedullary repair device against volar plating in the reconstruction of extra
      articular and simple articular distal radius fractures; a randomized pilot study.
AB  - PURPOSE: This prospective randomized pilot study reports our institutional
      experience and early results using Sonoma Wrx (Sonoma Orthopedic Products, Santa
      Rosa, CA) in the treatment of extra-articular and simple intra-articular distal
      radius fractures. MATERIAL AND METHODS: A total of 64 patients, were enrolled in
      the study. They were considered eligible if they had; unstable extra-articular
      distal radius fractures and simple intra-articular distal radius fractures
      suitable for closed reduction (AO types; A2.2, A2.3, A3.1 C2.1, C2.2). Patients
      in group I received intramedullary fixation using the Sonoma Wrx device and
      patients in group II received standard volar locking plate fixation. Radiographic
      criteria of acceptable healing were used for evaluation. RESULTS: Two groups were
      similar in terms of baseline characteristics. Mean time of operation was
      significantly shorter in Group 1 vs. in group 2 (36.81 +/- 7.11 vs. 48.97 +/- 5.9
      minutes, p = 0.001). Time to healing of the fracture was not different between
      two groups (5.45 +/- 1.09 vs. 5.70 +/- 1.04 weeks for Group 1 vs. 2, respectively
      p = 0.36). Overall complications occurred in 9 patients in group 1 and in 15
      patients in group 2 (p = 0.17). Follow-up was completed in all patients with a
      median time of 12 months and 13 months in group 1 and 2, respectively. On
      radiographic evaluation radial inclination, radial height and volar tilt were not
      significantly different between group 1 and 2, respectively. There were no
      significant differences between two groups in regard to wrist rotational degrees
      measured in last follow-up visit. CONCLUSION: Sonoma Wrx Device is reliable and
      effective in terms of achieving satisfactory outcomes in treatment of distal
      radius fractures. It may be reasonable to use this device to prevent
      complications that are related to extensive soft tissue dissection.

PMID- 24910217
TI  - How dead ends undermine power grid stability.
AB  - The cheapest and thus widespread way to add new generators to a high-voltage
      power grid is by a simple tree-like connection scheme. However, it is not
      entirely clear how such locally cost-minimizing connection schemes affect overall
      system performance, in particular the stability against blackouts. Here we
      investigate how local patterns in the network topology influence a power grid's
      ability to withstand blackout-prone large perturbations. Employing basin
      stability, a nonlinear concept, we find in numerical simulations of artificially
      generated power grids that tree-like connection schemes--so-called dead ends and
      dead trees--strongly diminish stability. A case study of the Northern European
      power system confirms this result and demonstrates that the inverse is also true:
      repairing dead ends by addition of a few transmission lines substantially
      enhances stability. This may indicate a topological design principle for future
      power grids: avoid dead ends.

PMID- 24910218
TI  - Back to basics for diabetes.

PMID- 24910219
TI  - Making cancer data count.

PMID- 24910216
TI  - Purinergic neuromuscular transmission in the gastrointestinal tract; functional
      basis for future clinical and pharmacological studies.
AB  - Nerve-mediated relaxation is necessary for the correct accomplishment of
      gastrointestinal (GI) motility. In the GI tract, NO and a purine are probably
      released by the same inhibitory motor neuron as inhibitory co-transmitters. The
      P2Y1 receptor has been recently identified as the receptor responsible for
      purinergic smooth muscle hyperpolarization and relaxation in the human gut. This
      finding has been confirmed in P2Y1 -deficient mice where purinergic
      neurotransmission is absent and transit time impaired. However, the mechanisms
      responsible for nerve-mediated relaxation, including the identification of the
      purinergic neurotransmitter(s) itself, are still debatable. Possibly different
      mechanisms of nerve-mediated relaxation are present in the GI tract. Functional
      demonstration of purinergic neuromuscular transmission has not been correlated
      with structural studies. Labelling of purinergic neurons is still experimental
      and is not performed in routine pathology studies from human samples, even when
      possible neuromuscular impairment is suspected. Accordingly, the contribution of
      purinergic neurotransmission in neuromuscular diseases affecting GI motility is
      not known. In this review, we have focused on the physiological mechanisms
      responsible for nerve-mediated purinergic relaxation providing the functional
      basis for possible future clinical and pharmacological studies on GI motility
      targeting purine receptors. 

PMID- 24910220
TI  - Ebola in west Africa: gaining community trust and confidence.

PMID- 24910221
TI  - The global implications of diabetes and cancer.

PMID- 24910223
TI  - Linong Ji: fighting to turn the tide against diabetes in China.

PMID- 24910224
TI  - Venezuela: violence, human rights, and health-care realities.

PMID- 24910225
TI  - Venezuela: violence, human rights, and health-care realities.

PMID- 24910226
TI  - Venezuela: violence, human rights, and health-care realities.

PMID- 24910227
TI  - Venezuela: violence, human rights, and health-care realities.

PMID- 24910228
TI  - Venezuela: violence, human rights, and health-care realities - Author's reply.

PMID- 24910229
TI  - A new era for organ transplantation in China.

PMID- 24910230
TI  - Delays in South Africa's plans to ban alcohol advertising.

PMID- 24910232
TI  - Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2
      diabetes.
AB  - Few trials of glucose-lowering drugs or strategies in people with type 2 diabetes
      have investigated cardiovascular outcomes, even though most patients die from
      cardiovascular causes despite the beneficial effects of lipid-reducing and blood
      pressure-lowering treatments. The evidence-based reduction in risk of
      microvascular disease with glucose lowering has resulted in guidelines worldwide
      recommending optimisation of glycosylated haemoglobin, but no trial results have
      shown unequivocal cardiovascular risk reduction with glucose lowering. However,
      results of the post-trial follow-up of the UK Prospective Diabetes Study, and of
      a meta-analysis of the four glucose-lowering outcome trials completed to date,
      suggest about a 15% cardiovascular relative risk reduction per 1% decrement in
      HbA1c. The 2008 US Food and Drug Administration industry guidance for licensing
      of antidiabetic drugs greatly increased the number of cardiovascular outcome
      trials in diabetes, but most trials opted for non-inferiority designs aiming
      primarily to show absence of cardiovascular toxicity in the shortest possible
      time. This unintended consequence of the new regulations has meant that the
      potential long-term benefits, and the possible risks of new therapies, are not
      being assessed effectively. Also, essential head-to-head trials of therapies for
      this complex progressive disease, to answer issues such as how best to achieve
      and maintain optimum glycaemia without promoting weight gain or hypoglycaemia,
      are not being undertaken. In this Series paper, we summarise randomised
      controlled cardiovascular outcome trials in type 2 diabetes, provide an overview
      of ongoing trials and their limitations, and speculate on how future trials could
      be made more efficient and effective. 

PMID- 24910233
TI  - Pathognomonic seizures in limbic encephalitis associated with anti-LGI1
      antibodies.

PMID- 24910231
TI  - Prevention and management of type 2 diabetes: dietary components and nutritional
      strategies.
AB  - In the past couple of decades, evidence from prospective observational studies
      and clinical trials has converged to support the importance of individual
      nutrients, foods, and dietary patterns in the prevention and management of type 2
      diabetes. The quality of dietary fats and carbohydrates consumed is more crucial
      than is the quantity of these macronutrients. Diets rich in wholegrains, fruits,
      vegetables, legumes, and nuts; moderate in alcohol consumption; and lower in
      refined grains, red or processed meats, and sugar-sweetened beverages have been
      shown to reduce the risk of diabetes and improve glycaemic control and blood
      lipids in patients with diabetes. With an emphasis on overall diet quality,
      several dietary patterns such as Mediterranean, low glycaemic index, moderately
      low carbohydrate, and vegetarian diets can be tailored to personal and cultural
      food preferences and appropriate calorie needs for weight control and diabetes
      prevention and management. Although much progress has been made in development
      and implementation of evidence-based nutrition recommendations in developed
      countries, concerted worldwide efforts and policies are warranted to alleviate
      regional disparities. 

PMID- 24910234
TI  - Ligand-free palladium-catalyzed aerobic oxidative coupling of carboxylic
      anhydrides with arylboronic acids.
AB  - We report a new, effective and environmentally friendly protocol for selective
      aerobic oxidative coupling of arylboronic acids with carboxylic anhydrides in the
      presence of ligand-free palladium catalyst. The aryl benzoates are obtained in
      good to excellent yields. 

PMID- 24910235
TI  - Brief report: Granulocyte-macrophage colony-stimulating factor drives monosodium
      urate monohydrate crystal-induced inflammatory macrophage differentiation and
      NLRP3 inflammasome up-regulation in an in vivo mouse model.
AB  - OBJECTIVE: To determine the role of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in the differentiation of inflammatory macrophages in an in vivo
      model of monosodium urate monohydrate (MSU) crystal-induced inflammation.
      METHODS: C57BL/6J mice were treated with either clodronate liposomes to deplete
      peritoneal macrophages or GM-CSF antibody and were then challenged by
      intraperitoneal injection of MSU crystals. Peritoneal lavage fluid was collected,
      and cellular infiltration was determined by flow cytometry. Purified resident and
      MSU crystal-recruited monocyte/macrophages were stimulated ex vivo with MSU
      crystals. The interleukin-1beta (IL-1beta) levels in lavage fluids and ex vivo
      assay supernatants were measured. GM-CSF-derived and macrophage colony
      stimulating factor (M-CSF)-derived macrophages were generated in vitro from bone
      marrow cells. Protein expression of IL-1beta, caspase 1, NLRP3, and ASC by in
      vitro- and in vivo-generated monocyte/macrophages was analyzed by Western
      blotting. RESULTS: Depletion of resident macrophages lowered MSU crystal-induced
      IL-1beta and GM-CSF levels in vivo as well as IL-1beta production by MSU crystal
      recruited monocytes stimulated ex vivo. GM-CSF neutralization in vivo decreased
      MSU crystal-induced IL-1beta levels and neutrophil infiltration. MSU crystal
      recruited monocyte/macrophages from GM-CSF-neutralized mice expressed lower
      levels of the macrophage marker CD115 and produced less IL-1beta following ex
      vivo stimulation. These monocytes exhibited decreased expression of NLRP3,
      pro/active IL-1beta, and pro/active caspase 1. In vitro-derived GM-CSF
      differentiated macrophages expressed higher levels of NLRP3, pro/active IL-1beta,
      and pro/active caspase 1 compared to M-CSF-differentiated macrophages.
      CONCLUSION: GM-CSF plays a key role in the differentiation of MSU crystal
      recruited monocytes into proinflammatory macrophages. GM-CSF production may
      therefore contribute to the exacerbation of inflammation in gout.

PMID- 24910236
TI  - Fungal mediated generation of mammalian metabolites of fenofibrate and enhanced
      pharmacological activity of the main metabolite fenofibric acid.
AB  - Different fungi viz. Aspergillus niger NCIM 589, A.ochraceous NCIM 1140,
      Cunninghamella blakesleeana NCIM 687, C. echinulata NCIM 691, Rhizopus stolonifer
      NCIM 880, Mucor rouxi MTCC 386, Trichothecium roseum NCIM 1147 were screened for
      their potential to biotransform anti-hyperlipidemia and anti-hypertriglyceridemia
      drug, fenofibrate to fenofibric acid, the active metabolite and other mammalian
      metabolites. Among the fungi screened C. blakesleeana transformed fenofibrate to
      fenofibric acid and other three metabolites. HPLC, LC-MS/MS analysis and previous
      reports confirmed the transformation of fenofibrate and metabolites as fenofibric
      acid (M1), reduced fenofibric acid (M2), reduced fenofibric acid taurine
      conjugate (M3), reduced fenofibric acid ester glucuronide (M4), the mammalian
      metabolites reported previously. The results proved the potential of
      C.blakesleeana NCIM 687 in the production of mammalian phase I (M1 and M2) and
      phase II (M3 and M4) metabolites in large quantities and also as an in vitro
      model for drug metabolism studies. 

PMID- 24910237
TI  - Application of a higher throughput approach to derive apparent Michaelis-Menten
      constants of isoform-selective p450-mediated biotransformation reactions in human
      hepatocytes.
AB  - A higher throughput platform was developed for the determination of K(M) values
      for isoformselective P450 substrates in human hepatocytes via incubation of the
      hepatocytes with substrates in 384- well plates and metabolite quantification by
      RapidFireTM mass spectrometry. Isoform-selective P450 substrates were incubated
      at 8 concentrations in triplicate with cryopreserved human hepatocytes from 16
      donors. The metabolic pathways examined were the CYP1A2-catalyzed tacrine 1
      hydroxylation, CYP2B6-catalyzed bupropion hydroxylation, CYP2C8-catalyzed
      amodiaquine N-deethylation, CYP2C9- catalyzed diclofenac 4'-hydroxylation, CYP2D6
      catalyzed dextromethorphan O-demethylation, and CYP3A4-catalyzed midazolam 1'
      hydroxylation. Typical saturation enzyme kinetics was observed for all the
      pathways evaluated. Individual differences in the apparent V(max) and K(M) values
      were observed among the human hepatocytes from each of the 16 individual donors,
      with no statistically significant gender- or age-associated differences. A
      "composite" K(M) value was calculated for each of the pathways via normalizing
      the individual activities to their respective V(max) values to develop "relative
      activities" followed by Michaelis-Menten analysis of the mean relative activities
      of the 16 donors at each of the 8 substrate concentrations. The resulting
      "composite" K(M) values for the P450 substrates may be used to guide in vitro
      P450 inhibition and induction studies and kinetic modeling of in vivo drug-drug
      interaction.

PMID- 24910238
TI  - Direct and rapid transcript analysis assay for CYP mRNA expression and
      inducibility in human primary hepatocytes.
AB  - Induction of cytochrome P450 (CYP) enzymes is commonly analyzed in cultured human
      primary hepatocytes (HPHs) by measuring CYP1A2, CYP2B6 and CYP3A4/3A5 activities
      after exposure to test and reference compounds. Because chemicals can both
      inhibit and induce CYP enzymes, this traditional approach fails to distinguish
      such simultaneous effects. Regulatory authorities have therefore suggested that
      measurement of CYP expression levels should complement activity measurements. We
      aimed to compare a hybridization and bead-based assay termed transcript analysis
      with the aid of affinity capture (TRAC) with the routinely used quantitative real
      time PCR (qRT-PCR) assay and to study its suitability for CYP induction studies
      on mRNA level. HPHs from three donors were treated with vehicle, reference
      substances omeprazole, phenobarbital and rifampicin and six test compounds on 48
      well plates. The mRNA expression of ten CYP isoforms important for drug
      metabolism was determined by TRAC and qRT-PCR methods in order to validate the
      novel TRAC method. The fold-increases of CYP mRNA levels showed a good
      correlation between the assays. With TRAC, the marker CYP mRNAs for induction
      could be easily detected from about 10 000 hepatocytes per sample, with a
      coefficient of variation below 10% between triplicates. Time spent for TRAC
      analysis was significantly shorter. Thus, TRAC is a sensitive and reproducible
      high-throughput assay, which enables accurate and direct detection of multiple
      mRNA targets simultaneously from large number of samples without enzymatic
      reactions inherent to qRT-PCR. It is a valuable method to study CYP induction and
      expandable to other genes relevant for drug metabolism and toxicity. 

PMID- 24910239
TI  - A new quaternary ammonium cysteine analogue as a trapping reagent for reactive
      metabolites screening.
AB  - The novel cysteine-cholamine (Cys-chol) trapping reagent was synthesized by
      coupling N-(tertbutoxycarbonyl)- S-trityl-L-cysteine with cholamine in the
      presence of HBTU (O-(benzotriazol-1-yl)- N,N,N',N'-tetramethyluronium
      hexafluorophosphate), and then deprotecting by trifluoroacetic acid. Cys-chol
      reagent enhanced the sensitivity of reactive metabolite screening 4 to 20 times
      without introducing additional sample preparation or derivatization steps.
      Retention of Cys-chol conjugates on reversed-phase column is higher than for
      respective GSH conjugates which helps in reduction of background interference.
      The use of Cys-chol trapping reagent can potentially improve sensitivity and
      specificity of routine reactive metabolite screening assay in drug discovery.

PMID- 24910240
TI  - Systematic review with meta-analysis: accuracy of interferon-gamma releasing
      assay and anti-Saccharomyces cerevisiae antibody in differentiating intestinal
      tuberculosis from Crohn's disease in Asians.
AB  - BACKGROUND AND AIMS: Distinguishing Crohn's disease (CD) from intestinal
      tuberculosis (ITB) is a clinical challenge. This meta-analysis assessed the
      clinical usefulness of Interferon-gamma releasing assay (IGRA) and anti
      Saccharomyces cerevisiae antibody (ASCA) in the diagnosis of ITB and CD,
      respectively. METHODS: Systematic search without language restriction was
      conducted in AMED, EBM, MEDLINE, EMBASE, and Google Scholar until September 2013.
      Studies that have evaluated performance of IGRA (QuantiFERON-TB Gold or T
      SPOT.TB) or ASCA in distinguishing ITB from CD were eligible. Main outcome
      measures included sensitivity and specificity. Random-effects models were used to
      combine estimates from studies with significant heterogeneity. Area under the
      curve (AUC) was used to measure accuracy of the tests. RESULTS: Eleven studies
      (five IGRA, three ASCA, three IGRA and ASCA) involving 1081 subjects were
      included. The pooled sensitivity, specificity, positive likelihood ratio, and
      negative likelihood ratio of IGRA for the diagnosis of ITB was 81% (95% CI, 75
      86%), 85% (95% CI, 81-89%), 6.02 (95% CI: 4.62-7.83), and 0.19 (95% CI: 0.10
      0.36), respectively. The AUC was 0.92. The pooled sensitivity and specificity of
      ASCA for the diagnosis of CD was 33% (95% confidence interval [CI], 27%-38%) and
      83% (95% CI, 77-88%), respectively with an AUC of 0.58. T-SPOT.TB showed a higher
      sensitivity than QuantiFERON-TB Gold for the diagnosis of ITB. CONCLUSIONS: IGRA
      and ASCA have a high specificity for the diagnosis of ITB. Both IGRA and ASCA may
      have a supplementary role in the differential diagnosis between ITB and CD when
      conventional workup is not diagnostic.

PMID- 24910241
TI  - Place field stability requires the metabotropic glutamate receptor, mGlu5.
AB  - The metabotropic glutamate (mGlu) receptors are critically involved in enabling
      the persistency of forms of synaptic plasticity that are believed to underlie
      hippocampus-dependent memory. These receptors and in particular, mGlu5, are also
      required for hippocampus-dependent learning and memory. In the hippocampus,
      synaptic plasticity is one of the mechanisms by which spatial information may be
      represented. Another mechanism involves increased firing of place cells. Place
      cells increase their firing activity when an animal is in a specific spatial
      location. Inhibition of factors that are essential for synaptic plasticity, such
      as N-methyl-d-aspartate receptors or protein synthesis, also impair place cell
      activity. This raises the question as to whether mGlu receptors, that are so
      important for synaptic plasticity and spatial memory, are also important for
      place cell encoding. We examined location-dependent place cell firing i.e. place
      fields. We observed that antagonism of mGlu5, using 2-methyl-6-(phenylethynyl)
      pyridine (MPEP) had no effect on place field profiles in a familiar environment.
      However, in a novel environment mGlu5-antagonism affected long-term place field
      stability, reduced place cell firing and spatial information. These data strongly
      suggest a role for mGlu5 in the mechanisms underlying informational content and
      long-term stability of place fields, and add to evidence supporting the
      importance of these receptors for hippocampal function.

PMID- 24910244
TI  - Coadministration of beta-asarone and levodopa increases dopamine in rat brain by
      accelerating transformation of levodopa: a different mechanism from Madopar.
AB  - The aim of the present study was to investigate the effect of coadministration of
      beta-asarone and levodopa (l-dopa) on increasing dopamine (DA) in the striatum of
      healthy rats. Rats were randomly divided into four groups: (i) a normal group,
      administered normal saline; (ii) a Madopar group, administered 75 mg/kg Madopar
      (l-dopa : benserazide, 4 : 1); (iii) an l-dopa group, administered 60 mg/kg l
      dopa; and (iv) a group coadministered 15 mg/kg beta-asarone and 60 mg/kg l-dopa.
      All drugs (or normal saline) were administered intragastrically twice a day for 7
      days. Then, plasma and striatum concentrations of DA, l-dopa, 5-hydroxytryptamine
      (5-HT), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), tyrosine
      hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase B
      (MAO-B) were determined. In the group coadministered beta-asarone and l-dopa,
      there was a decline in plasma and striatal concentrations of l-dopa; however, DA
      and DOPAC concentrations increased in the striatum and plasma and plasma HVA
      concentrations increased, whereas there was no significant change in striatal
      levels. Concentrations of 5-HT in the striatum and plasma were similar in the
      coadministered and Madopar-treated groups. In addition, plasma and striatal COMT
      levels decreased after coadministration of beta-asarone and l-dopa, whereas there
      were no significant differences in MAO-B concentrations among groups.
      Furthermore, coadministration of beta-asarone and l-dopa increased plasma TH
      concentrations. Altogether, beta-asarone affects the conversion of l-dopa to DA
      by modulating COMT activity and DA metabolism. The mechanism of coadministration
      is different from that of Madopar in Parkinson's disease (PD) treatment. Thus,
      the coadministration of beta-asarone and l-dopa may be beneficial in the
      treatment of PD. 

PMID- 24910242
TI  - Liver damage, inflammation, and enhanced tumorigenesis after persistent mTORC1
      inhibition.
AB  - Obesity can result in insulin resistance, hepatosteatosis, and nonalcoholic
      steatohepatitis (NASH) and increases liver cancer risk. Obesity-induced insulin
      resistance depends, in part, on chronic activation of mammalian target of
      rapamycin complex 1 (mTORC1), which also occurs in human and mouse hepatocellular
      carcinoma (HCC), a frequently fatal liver cancer. Correspondingly, mTORC1
      inhibitors have been considered as potential NASH and HCC treatments. Using a
      mouse model in which high-fat diet enhances HCC induction by the hepatic
      carcinogen DEN, we examined whether mTORC1 inhibition attenuates liver
      inflammation and tumorigenesis. Notably, rapamycin treatment or hepatocyte
      specific ablation of the specific mTORC1 subunit Raptor resulted in elevated
      interleukin-6 (IL-6) production, activation of signal transducer and activator of
      transcription 3 (STAT3), and enhanced HCC development, despite a transient
      reduction in hepatosteatosis. These results suggest that long-term rapamycin
      treatment, which also increases IL-6 production in humans, is unsuitable for
      prevention or treatment of obesity-promoted liver cancer.

PMID- 24910245
TI  - Design and synthesis of D-ring steroidal isoxazolines and oxazolines as potential
      antiproliferative agents against LNCaP, PC-3 and DU-145 cells.
AB  - Two series of novel steroidal isoxazolines and oxazolines were synthesized
      through different routes from dehydroepiandrosterone acetate and pregnenolone
      acetate, respectively. The synthesis of the analogs of both series is multistep
      and proceeds in good overall yields. While the key step in the synthesis of
      former is the cycloaddition of aromatic nitrile oxides across alpha,beta
      unsaturated olefins, it is the condensation of alpha,beta-azidoalcohols with
      aromatic aldehydes in the later. Compounds of both the series were tested for
      their cytotoxic activities against LNCaP, PC-3 and DU-145 prostate cancer cell
      lines. Amongst all the compounds of both the series screened for their prostate
      cancer activity, compound 6a, 6e and 12a are the most active especially against
      LNCaP and DU-145 cancer cell lines. 

PMID- 24910243
TI  - The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct
      roles in obesity.
AB  - Metabolic disorders, including obesity and insulin resistance, have their basis
      in dysregulated lipid metabolism and low-grade inflammation. In a microarray
      search of unique lipase-related genes whose expressions are associated with
      obesity, we found that two secreted phospholipase A2s (sPLA2s), PLA2G5 and
      PLA2G2E, were robustly induced in adipocytes of obese mice. Analyses of Pla2g5(-/
      ) and Pla2g2e(-/-) mice revealed distinct roles of these sPLA2s in diet-induced
      obesity. PLA2G5 hydrolyzed phosphatidylcholine in fat-overladen low-density
      lipoprotein to release unsaturated fatty acids, which prevented palmitate-induced
      M1 macrophage polarization. As such, PLA2G5 tipped the immune balance toward an
      M2 state, thereby counteracting adipose tissue inflammation, insulin resistance,
      hyperlipidemia, and obesity. PLA2G2E altered minor lipoprotein phospholipids,
      phosphatidylserine and phosphatidylethanolamine, and moderately facilitated lipid
      accumulation in adipose tissue and liver. Collectively, the identification of
      "metabolic sPLA2s" adds this gene family to a growing list of lipolytic enzymes
      that act as metabolic coordinators. 

PMID- 24910246
TI  - A study on correlation between 2D and 3D gamma evaluation metrics in patient
      specific quality assurance for VMAT.
AB  - In this study, we investigated the correlation between 2-dimensional (2D) and 3D
      gamma analysis using the new PTW OCTAVIUS 4D system for various parameters. For
      this study, we selected 150 clinically approved volumetric-modulated arc therapy
      (VMAT) plans of head and neck (50), thoracic (esophagus) (50), and pelvic
      (cervix) (50) sites. Individual verification plans were created and delivered to
      the OCTAVIUS 4D phantom. Measured and calculated dose distributions were compared
      using the 2D and 3D gamma analysis by global (maximum), local and selected
      (isocenter) dose methods. The average gamma passing rate for 2D global gamma
      analysis in coronal and sagittal plane was 94.81% +/- 2.12% and 95.19% +/- 1.76%,
      respectively, for commonly used 3-mm/3% criteria with 10% low-dose threshold.
      Correspondingly, for the same criteria, the average gamma passing rate for 3D
      planar global gamma analysis was 95.90% +/- 1.57% and 95.61% +/- 1.65%. The
      volumetric 3D gamma passing rate for 3-mm/3% (10% low-dose threshold) global
      gamma was 96.49% +/- 1.49%. Applying stringent gamma criteria resulted in higher
      differences between 2D planar and 3D planar gamma analysis across all the global,
      local, and selected dose gamma evaluation methods. The average gamma passing rate
      for volumetric 3D gamma analysis was 1.49%, 1.36%, and 2.16% higher when compared
      with 2D planar analyses (coronal and sagittal combined average) for 3mm/3%
      global, local, and selected dose gamma analysis, respectively. On the basis of
      the wide range of analysis and correlation study, we conclude that there is no
      assured correlation or notable pattern that could provide relation between planar
      2D and volumetric 3D gamma analysis. Owing to higher passing rates, higher action
      limits can be set while performing 3D quality assurance. Site-wise action limits
      may be considered for patient-specific QA in VMAT.

PMID- 24910247
TI  - Dose variations caused by setup errors in intracranial stereotactic radiotherapy:
      a PRESAGE study.
AB  - Stereotactic radiotherapy (SRT) requires tight margins around the tumor, thus
      producing a steep dose gradient between the tumor and the surrounding healthy
      tissue. Any setup errors might become clinically significant. To date, no study
      has been performed to evaluate the dosimetric variations caused by setup errors
      with a 3-dimensional dosimeter, the PRESAGE. This research aimed to evaluate the
      potential effect that setup errors have on the dose distribution of intracranial
      SRT. Computed tomography (CT) simulation of a CIRS radiosurgery head phantom was
      performed with 1.25-mm slice thickness. An ideal treatment plan was generated
      using Brainlab iPlan. A PRESAGE was made for every treatment with and without
      errors. A prescan using the optical CT scanner was carried out. Before treatment,
      the phantom was imaged using Brainlab ExacTrac. Actual radiotherapy treatments
      with and without errors were carried out with the Novalis treatment machine.
      Postscan was performed with an optical CT scanner to analyze the dose
      irradiation. The dose variation between treatments with and without errors was
      determined using a 3-dimensional gamma analysis. Errors are clinically
      insignificant when the passing ratio of the gamma analysis is 95% and above.
      Errors were clinically significant when the setup errors exceeded a 0.7-mm
      translation and a 0.5 degrees  rotation. The results showed that a 3-mm
      translation shift in the superior-inferior (SI), right-left (RL), and anterior
      posterior (AP) directions and 2 degrees  couch rotation produced a passing ratio
      of 53.1%. Translational and rotational errors of 1.5mm and 1 degrees ,
      respectively, generated a passing ratio of 62.2%. Translation shift of 0.7mm in
      the directions of SI, RL, and AP and a 0.5 degrees  couch rotation produced a
      passing ratio of 96.2%. Preventing the occurrences of setup errors in
      intracranial SRT treatment is extremely important as errors greater than 0.7mm
      and 0.5 degrees  alter the dose distribution. The geometrical displacements
      affect dose delivery to the tumor and the surrounding normal tissues.

PMID- 24910248
TI  - The use of chlorobenzene as a probe molecule in molecular dynamics simulations.
AB  - We map ligand binding sites on protein surfaces in molecular dynamics simulations
      using chlorobenzene as a probe molecule. The method was validated on four
      proteins. Two types of affinity maps that identified halogen and hydrophobic
      binding sites on proteins were obtained. Our method could prove useful for the
      discovery and development of halogenated inhibitors. 

PMID- 24910249
TI  - Plasmon mediated shape and size selective synthesis of icosahedral silver
      nanoparticles via oxidative etching and their 1-D transformation to pentagonal
      pins.
AB  - A size- and shape-selective synthesis of pentagonally twinned silver icosahedral
      nanoparticles (AgIhNPs), one of the five platonic solid morphologies, has been
      developed by integrating three key factors: nuclei templating by copper,
      photochemical development using violet LED light and chemical oxidative etching.
      The presence of copper is essential for AgIhNP shape selection via the promotion
      of icosahedral nuclei in precursor NPs. Violet light (401-410 nm) is crucial to
      promote plasmonic selection of near-spherical AgIhNPs. Oxidative etching with
      hydrogen peroxide and photochemical reduction with citrate establishes a red-ox
      equilibrium for the photochemical selection of AgIhNPs. The addition of chloride
      ions improves size- and shape-selectivity. Finally, the demonstration of 1-D
      growth of AgIhNPs to pentagonal pins initiated at AgIhNP pentagonal-twinned
      defects highlights a universal role of twinned defects for the formation of
      anisotropic nanoparticles. 

PMID- 24910250
TI  - Molecular characterization of human respiratory syncytial virus subtype B: a
      novel genotype of subtype B circulating in China.
AB  - Human respiratory syncytial virus (HRSV) is major pathogen of lower respiratory
      tract infections in infants and young children worldwide. There have been many
      studies regarding HRSV subgroup A (HRSV-A) G protein genetic variability but
      little information about HRSV subtype B (HRSV-B) G protein genetic diversity and
      molecular evolution in China. Thus, a survey of the molecular epidemiology and
      evolution of the G protein in China is of high importance. In this study, the
      circulation and genetic diversity of HRSV in Chongqing, Southwestern China, from
      June 2009 to May 2013, were investigated. A total of 3,167 nasopharyngeal
      aspirates were obtained in this study, and it was found that HRSV-B predominated
      in the 2009-2010 and 2012-2013 epidemic seasons. This study identified the
      genetic variability of the glycoprotein G gene among 102 HRSV-B strains isolated
      by cell culture from Chongqing nasopharyngeal aspirates, and 68 Chinese HRSV-B
      sequences were deposited in GenBank. Genotyping and phylogenetic analysis
      revealed that the HRSV-B strains were clustered into three genotypes: BA (n =
      111, 65.29%), GB3 (n = 5, 2.94%), and a new GB genotype (n = 54, 31.77%) named
      GB5. The GB5 strains varied from other genotypes in the central conserved region
      and N-glycosylation sites. The estimated evolutionary rate of Chinese HRSV-B was
      2.01 * 10(-3) nucleotide substitutions/site/year, which is similar to the reports
      from Belgium and the Netherlands with 1.95 * 10(-3) and 2.78 * 10(-3) nucleotide
      substitutions/site/year, respectively. This study provides data on the
      circulating pattern and molecular characterization of HRSV-B genotypes in China
      during four consecutive years and may contribute to HRSV vaccine development.

PMID- 24910251
TI  - Incidental renal neoplasms: is there a need for routine screening? A Danish
      single-center epidemiological study.
AB  - On the basis of associations between tumor size, pathological stage, histological
      subtype and tumor grade in incidentally detected renal cell carcinoma vs
      symptomatic renal cell carcinoma, we discussed the need for a screening program
      of renal cell carcinoma in Denmark. We analyzed a consecutive series of 204
      patients with renal tumors in 2011 and 2012. The tumors were classified according
      to detection mode: symptomatic and incidental and compared to pathological
      parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were
      incidental. Information was not available in two patients. In the incidental
      group, the size (p<0.05), pathological stage (p<0.001), Fuhrman grading
      (p<0.0001) and Leibovich score (p<0.0001) were lower than in those causing
      symptoms. Significantly less in the incidental group had metastasis at follow-up
      (p<0.0001). Incidentally discovered RCC constitute a major part of kidney tumors.
      They have a more favorable prognosis than symptomatic tumors and seem to be
      discovered in an earlier phase. Needle core biopsy is an accurate technique for
      distinguishing between malignant and benign tumors and is recommendable for
      smaller incidental tumors. Screening may help detect RCC at an earlier stage.

PMID- 24910252
TI  - Immunology and pathogenesis of canine demodicosis.
AB  - Demodex mites colonized the hair follicles and sebaceous glands of mammals
      millions of years ago and have remained relatively unchanged in this protected
      ecologic niche since then. The host immune system detects and tolerates their
      presence. Toll-like receptor-2 of keratinocytes has been demonstrated to
      recognize mite chitin and to elicit an innate immune response. The subsequent
      acquired immune response is poorly understood at present, but there is
      experimental and clinical evidence that this is the main mechanism in the control
      of mite proliferation. A transgenic mouse model (STAT(-/-) /CD28(-/-) ) has
      demonstrated that the immune response is complex, probably involving both
      cellular and humoral mechanisms and requiring the role of co-stimulatory
      molecules (CD28). It is known that a genetic predisposition for developing canine
      juvenile generalized demodicosis exists; however, the primary defect leading to
      the disease remains unknown. Once the mite proliferation is advanced, dogs show a
      phenotype that is similar to the T-cell exhaustion characterized by low
      interleukin-2 production and high interleukin-10 and transforming growth factor
      beta production by lymphocytes, as described in other viral and parasitic
      diseases. Acaricidal treatment (macrocyclic lactones) decreases the antigenic
      load and reverses T-cell exhaustion, leading to a clinical cure. Although in
      recent years there have been significant advances in the management and
      understanding of this important and complex canine disease, more research in
      areas such as the aetiology of the genetic predisposition and the immune control
      of the mite populations is clearly needed. 

PMID- 24910253
TI  - Preliminary validity and reliability of a Thai Berlin questionnaire in stroke
      patients.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a major risk factor for stroke. The
      Berlin Questionnaire (BQ) has been shown to be a valid tool to screen for OSA.
      The literature has limited data on using the BQ in stroke patients; particularly
      in Thailand and other developing countries. Here, we aimed to develop a Thai
      language Berlin Questionnaire (Thai BQ) and to preliminarily assess construct
      validity, test-retest reliability and the agreement of the Thai BQ with the Thai
      Epworth Sleepiness Scale (Thai ESS), another screening tool for OSA. METHODS: A
      hospital-based cross-sectional study was performed from January to July, 2011.
      One hundred first-ever stroke patients, including acute and chronic cases, and
      their caregivers were enrolled. The Thai BQ was developed using the forward
      backward translation method. Evaluation of construct validity was done by factor
      analysis. Internal consistency of the Thai BQ and the Thai ESS were evaluated
      using Cronbach's alpha coefficient. Test-retest reliability and the agreement of
      the Thai BQ and the Thai ESS were evaluated using Cohen's kappa coefficient.
      RESULTS: Factor analysis identified 4 main factors: Factor 1-Snoring behaviour;
      Factor 2-Sleepiness during driving; Factor 3-Daytime fatigue; and Factor 4
      Hypertension or obesity. Cronbach's alpha coefficient was 0.77 (95% confidence
      interval (CI) = 0.69-0.83) and Cohen's kappa coefficient was 0.86 (95% CI = 0.74
      0.98) in the Thai BQ. Cronbach's alpha coefficient was 0.59 (95% CI = 0.45-0.70)
      and the Cohen's kappa coefficient was 0.81 (95% CI = 0.60-1.00) in the Thai ESS.
      The agreement between the Thai ESS and the Thai BQ was fair. CONCLUSIONS: The
      Thai BQ is a valid and reliable tool to screen for OSA in stroke patients. As
      factor analysis revealed 4 factors in contrast to the 3 factors in the original
      BQ, further modification of the Thai BQ is required.

PMID- 24910254
TI  - Motor speech impairment, activity, and participation in children with cerebral
      palsy.
AB  - The present study used a population-based sample of children with cerebral palsy
      (CP) to estimate the prevalence of motor speech impairment and its association
      with activity and participation. A sample of 79 Victorian children aged 4 years
      11 months to 6 years 5 months was recruited through the Victorian CP Register.
      The presence of motor speech impairment was recorded using the Viking Speech
      Scale (VSS). Activity and participation outcomes included speech intelligibility
      (the National Technical Institute for the Deaf rating scale, NTID), the
      Functional Communication Classification System (FCCS) and Communication Function
      Classification System (CFCS). A parent completed rating scale was used to examine
      the association between motor speech impairment and participation. Ninety per
      cent (71/79) of children demonstrated a motor speech impairment. Strong
      associations were found between the VSS and NTID (< .001), CFCS (< .001), and
      FCCS levels (<.001). VSS levels III-IV were significantly associated with
      restrictions in home, school, and community-based participation as perceived by
      parents. Although some diversity in activity and participation outcomes was
      observed within specific VSS levels, the results of this study suggested that
      children with mild motor speech impairments are more likely to demonstrate
      superior activity and participation outcomes compared to children with moderate
      or severe deficits.

PMID- 24910255
TI  - Consonant production and overall speech characteristics in school-aged children
      with cerebral palsy and speech impairment.
AB  - The aim of the present study was to investigate the speech characteristics of
      school-aged children with cerebral palsy (CP) and speech impairment at various
      cognitive levels. Nineteen children with a mean age of 11;2 years (9;2-12;9
      years) with spastic, dyskinetic, and ataxic CP and speech impairment
      participated. Phonetic transcription of oral consonants, ratings of
      hypernasality, and severity of overall dysarthria, together with free field
      descriptions of respiration, voice quality, and prosody, were performed
      independently by two speech-language pathologists. The non-verbal cognitive level
      was also studied. More than half of the children had large problems with the
      articulation of consonants, and the children with ataxic CP were most affected.
      The majority was rated as having dysarthria, mostly mild, but hypernasality was
      rare. Gross motor problems were not significantly associated with the
      articulation of consonants or the severity of dysarthria, whereas non-verbal
      cognitive level was. This underlines the importance of taking non-verbal
      cognitive level into account, when designing individual speech treatment programs
      for this group of children. Finally, a careful examination of the articulation of
      consonants is recommended in order to study speech production thoroughly in
      children with CP.

PMID- 24910256
TI  - Complete determination of molecular orbitals by measurement of phase symmetry and
      electron density.
AB  - Several experimental methods allow measuring the spatial probability density of
      electrons in atoms, molecules and solids, that is, the absolute square of the
      respective single-particle wave function. But it is an intrinsic problem of the
      measurement process that the information about the phase is generally lost during
      the experiment. The symmetry of this phase, however, is a crucial parameter for
      the knowledge of the full orbital information in real space. Here, we report on a
      key experiment that demonstrates that the phase symmetry can be derived from a
      strictly experimental approach from the circular dichroism in the angular
      distribution of photoelectrons. In combination with the electron density derived
      from the same experiment, the full quantum mechanical wave function can thus be
      determined experimentally. 

PMID- 24910257
TI  - CD3G gene defects in familial autoimmune thyroiditis.
AB  - The patients with CD3gamma deficiency can present with different clinical
      findings despite having the same homozygous mutation. We report three new
      CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+
      immunodeficiency and their variable clinical and cellular phenotypes despite the
      same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a
      previously reported non-consanguineous family with two CD3gamma-deficient
      siblings with the same mutation. The median age at diagnosis was 11 years (14
      months-20 years). We found all five patients to display autoimmunity: autoimmune
      thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune
      thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic
      syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as
      well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCRalphabeta+T
      cell percentages were low in all patients, only one had lymphopenia and 3 had
      CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple
      autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%),
      and frequent autoimmunity in family members not available for testing (n = 5, in
      80%). The results suggest that CD3G should be studied as a candidate gene for
      autoimmunity and that CD3gamma deficiency should be considered among other
      primary immunodeficiencies with predominantly autoimmune manifestations. 

PMID- 24910258
TI  - A method for measuring difference in activity of phenolic and non- phenolic
      groups through 2,2' azino-bis-(3-ethyl-benzothiazoline-6- sulphonate) radical
      cation.
AB  - A 2, 2'azino-bis-(3-ethyl-benzothiazoline-6-sulphonate) radical cation-based
      method was optimized in 96 well plates to evaluate the comparative scavenging
      potential of phenolic and non-phenolic group of molecules with respect to
      control. The interactions of these molecules with ABTS radical cation were
      quantified on the basis of their relative influence on the bleaching of a bluish
      green color complex in a structure- and dose-dependent manner. Experimentally,
      the developed assay provided evidence that phenolic molecules are more reactive
      with ABTS radical than non-phenolic compounds because of their resonance and
      hyper-conjugation effects. 

PMID- 24910259
TI  - Isolation of lactic acid-tolerant Saccharomyces cerevisiae from Cameroonian
      alcoholic beverage.
AB  - We investigated yeast strains used in Cameroonian microbreweries, and identified
      a Saccharomyces cerevisiae strain (OCY3) with an excellent capacity for alcoholic
      fermentation. OCY3 showed higher tolerance to lactic acid and better fermentation
      performance under acidic conditions than a representative Japanese sake yeast,
      Kyokai No. 7, and a wine yeast, EC1118. 

PMID- 24910260
TI  - Enzymatic synthesis of 2'-deoxyuridine by whole cell catalyst co-expressing
      uridine phosphorylase and thymidine phosphorylase through auto-induction system.
AB  - Genes encoding uridine phosphorylase (UP) and thymidine phosphorylase (TP) from
      Escherichia coli K12 were cloned and recombined respectively into plasmids pET
      21a(+) and pET-28a(+). The recombinant plasmids BL21/pET21a-UP and BL21/pET28a-TP
      were co-transformed into E. coli BL21(DE3) to construct highly effective BTU
      strain (BL21/pET28a-TP, pET21a-UP) overexpressing both of UP and TP. BTU was
      cultivated in ZYM-Fe-5052 medium for 10 h and used as catalyst to synthesize 2'
      deoxyuridine (dUR). It was found to increase the productivity of dUR by 8-9 fold
      when compared to wild E. coli K12 and E. coli BL21(DE3) strains. A series of
      experiments were carried out to find out the optimal conditions for synthesis of
      dUR. At 50 degrees C, with 0.250/00 dry wt./v to catalyze the reaction of 2:1
      beta-thymidine: uracil (60 mM beta-thymidine, 30 mM uracil), the conversion rate
      of dUR would reach 61.6% at 1 h, which was much higher than the rates obtained by
      BTU strain cultured in LB medium and induced by IPTG. This result proved co
      expression and auto-induction were efficient methods in enhancing the expression
      quantity and activity of nucleoside phosphorylases, and they also had significant
      implications for large-scale industrial production of dUR and synthesis of other
      nucleoside derivatives.

PMID- 24910261
TI  - Predicting Change in Marital Satisfaction Throughout Emotionally Focused Couple
      Therapy.
AB  - Emotionally focused couple therapy (EFT) is an empirically validated approach to
      couple therapy that uses attachment theory to understand the needs and emotions
      of romantic partners. EFT is recognized as one of the most effective approaches
      to couple therapy, but to guide therapists in their use of EFT, a theoretically
      based model to predict change is needed. This study tested such a model by
      recruiting 32 couples, and 14 therapists who provided approximately 21 sessions
      of EFT. Couples completed self-report measures of marital satisfaction,
      attachment security, relationship trust, and emotional control at pre- and
      posttherapy and after each therapy session. Results of hierarchical linear
      modeling suggested that individuals higher on self-report attachment anxiety and
      higher levels of emotional control had greater change in marital satisfaction
      across EFT sessions. Assessing attachment security at the start of therapy will
      inform therapists of the emotion regulating strategies used by couples and may
      help couples achieve positive outcomes from EFT. 

PMID- 24910263
TI  - Morphometric scores for renal tumors: what does the radiologist need to know?
AB  - Numerous therapeutic options are possible in the treatment of renal carcinomas
      including radical nephrectomy, partial nephrectomy, cryoablation, radiofrequency,
      active follow-up and among surgical treatments, different approaches may be used
      such as laparotomy, laparoscopy, robotic-assisted intervention. The choice
      between these different procedures is partially based on the anatomic conditions
      of the tumors. Different anatomic scores determined from cross-sectional imaging
      have been built to predict the complexity of the surgical procedure. The goals of
      this article are to review the relevant morphologic pattern for management of
      patients with renal tumors, to know how to calculate these different scores and
      to understand the clinical applications of these scores. 

PMID- 24910262
TI  - Molecular mechanisms of activity-dependent changes in dendritic morphology: role
      of RGK proteins.
AB  - The nervous system has the amazing capacity to transform sensory experience from
      the environment into changes in neuronal activity that, in turn, cause long
      lasting alterations in neuronal morphology. Recent findings indicate that,
      surprisingly, sensory experience concurrently activates molecular signaling
      pathways that both promote and inhibit dendritic complexity. Historically, a
      number of positive regulators of activity-dependent dendritic complexity have
      been described, whereas the list of identified negative regulators of this
      process is much shorter. In recent years, there has been an emerging appreciation
      of the importance of the Rad/Rem/Rem2/Gem/Kir (RGK) GTPases as mediators of
      activity-dependent structural plasticity. In the following review, we discuss the
      traditional view of RGK proteins, as well as our evolving understanding of the
      role of these proteins in instructing structural plasticity. 

PMID- 24910264
TI  - Three-dimensional saturation transfer 31P-MRI in muscles of the lower leg at 3.0
      T.
AB  - The creatine kinase (CK) reaction plays a critical role in skeletal muscle
      function, and can be studied non-invasively using phosphorus ((31)P) saturation
      transfer (ST) techniques. However, due to the low MR sensitivity of the (31)P
      nucleus, most studies on clinically approved magnetic fields (<=3.0 T) have been
      performed with coarse resolution and limited tissue coverage. However, such
      methods are not able to detect spatially resolved metabolic heterogeneities,
      which may be important in diseases of the skeletal muscle. In this study, our aim
      was to develop and implement a (31)P-MRI method for mapping the kinetics of the
      CK reaction, and the unidirectional phosphocreatine (PCr) to adenosine
      triphosphate (ATP) metabolic fluxes in muscles of the lower leg on a clinical 3.0
      T MR scanner. We imaged the lower leg muscles of ten healthy volunteers (total
      experimental time: 40 min, nominal voxel sizes 0.5 mL), and found statistically
      significant differences between the kinetics of the CK reaction among muscle
      groups. Our developed technique may allow in the future the early detection of
      focal metabolic abnormalities in diseases that affect the function of the
      skeletal muscle.

PMID- 24910265
TI  - Intense Foxp3+ CD25+ regulatory T-cell infiltration is associated with high-grade
      cutaneous squamous cell carcinoma and counterbalanced by CD8+/Foxp3+ CD25+ ratio.
AB  - BACKGROUND: Recent reports have revealed the therapeutic potential of cell
      mediated immunity in neoplasms such as cutaneous squamous cell carcinoma (SCC).
      OBJECTIVES: To define the antigenic coexpression of regulatory T cells (Tregs)
      and plasmacytoid dendritic cells (pDCs) and assess the CD8(+) /Foxp3(+) CD25(+)
      cell ratio at peritumoral and intratumoral levels in order to investigate a
      correlation with the aggressiveness of SCC tumours. METHODS: We evaluated the
      content and distribution of Foxp3(+) CD25(+) Treg and CD123(+) pDC infiltration
      and assessed CD8(+) /Foxp3(+) CD25(+) cell ratio at peritumoral and intratumoral
      levels in 40 SCCs (20 well-differentiated, G1; and 20 moderately to poorly
      differentiated, G2-G3) to investigate a correlation with their aggressiveness. We
      determined the profiles of Tregs and CD123(+) cells; immunostained for CD4, CD8,
      CD123, interleukin (IL)-1 and transforming growth factor (TGF)-beta1; and
      unequivocally double stained for Foxp3CD25. RESULTS: Peritumorally, CD4, CD8 and
      Foxp3 expression showed no difference between the two groups. CD123(+) cells were
      fewer in G2-G3 (P = 0.0005), while Foxp3(+) CD25(+) cells were more numerous (P =
      0.0005). The Foxp3(+) CD25(+) /Foxp3(+) ratio was higher in G2-G3 cases (P =
      0.0005), confirming the trend in this group of activated T lymphocytes towards
      total Treg Foxp3(+) cells, while the CD8(+) /Foxp3(+) CD25(+) ratio was higher in
      G1 (P = 0.0005). Intratumorally, CD4(+) and CD8(+) cells infiltrated G2-G3 (P =
      0.048) more than G1 (P = 0.004), whereas almost all cells were CD123 negative.
      Regarding Foxp3CD25, TGF-beta1 and IL-10, they were less expressed in G1, whereas
      they were positive in G2-G3 (P < 0.05). The CD8(+) /Foxp3(+) CD25(+) ratio was
      similar to that observed in peritumoral infiltration. CONCLUSIONS: Our data
      suggest that intratumoral recruitment of Tregs, high expression of TGF-beta1 and
      IL-10, almost negative CD123+, and a low CD8(+) /Foxp3(+) CD25(+) T-cell ratio
      may contribute to the aggressiveness of cutaneous SCC, as already evidenced for
      other solid tumours.

PMID- 24910266
TI  - Mucosal leishmaniasis of the lip: an emerging clinical form in Tunisia.
AB  - BACKGROUND: Mucosal leishmaniasis (ML), which mostly occurs in the New World, is
      mainly associated with Leishmania braziliensis. Primary lip ML is very rare in
      the Mediterranean basin and particulary in Tunisia despite the endemicity of both
      cutaneous and visceral leishmaniasis in this area. OBJECTIVES: To highlight a
      recent emergence of primary lip ML in Tunisia, to describe its epidemiological
      and clinical features and to identify the causative Leishmania species. METHODS:
      Epidemiological, clinical and therapeutic data of 10 cases presenting a ML of the
      lip were collected. Diagnosis confirmation of leishmaniasis was obtained by
      microscopic examination of Leishmania parasites in Giemsa stained smears of the
      lesion sampling and in cutaneous biopsies. Polymerase chain reaction (PCR)
      detecting Leishmania DNA directly from dermal scraping was also performed for
      diagnosis and species identification. RESULTS: Seven men and three women with lip
      ML were diagnosed during the last 6 years (2008-2013). The mean age was 29.7
      years. Clinical presentation was characterized by an infiltrated and ulcerated
      plaque leading to macrocheilitis involving the upper lip in eight cases and the
      lower lip in two cases. Mean diagnosis delay was 6.9 months. PCR identified L.
      infantum in seven cases and L. major in two cases. Seven patients received
      intramuscular injections of meglumine antimoniate (MA) and three patients
      received both MA intralesional injections of MA and cryotherapy. A clinical
      remission was rapidly observed in all cases (on average in 2.2 months).
      CONCLUSIONS: Primary lip ML is emerging in Tunisia. Macrocheilitis of the upper
      lip is the main clinical presentation. PCR revealed more sensitive than direct
      examination in the diagnosis of such form (P < 0.01). Leishmania infantum was the
      most identified species (7 cases) while L major was involved in only two lesions.
      A benign local evolution and a rapid recovery were observed in all cases after MA
      treatment.

PMID- 24910267
TI  - Cytomegalovirus immune reconstitution inflammatory syndrome manifesting as acute
      appendicitis in an HIV-infected patient.
AB  - BACKGROUND: Appendicitis occurs with increased frequency in HIV infected compared
      to HIV uninfected persons. CMV-related appendicitis specifically presents with
      typical appendicitis symptoms including surgical abdomen, fever and leukocytosis
      and may have a more severe course with higher mortality than other types of
      infective appendicitis. We report the first case of CMV appendicitis as a
      manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS). CASE
      PRESENTATION: The patient was a 38 year old woman with a recent diagnosis of HIV
      infection who complained of right lower quadrant pain, anorexia, nausea and
      fevers two weeks after initiating antiretroviral therapy. Acute appendicitis was
      suspected and the patient underwent an appendectomy. Pathologic examination of
      the resected appendiceal tissue demonstrated inflammation with perforation and
      cytopathic changes typical of CMV that were positive for CMV by immunostain. This
      presentation of CMV abruptly after antiretroviral therapy initiation with a
      pronounced cellular infiltration of the tissue, is consistent with CMV-IRIS
      presenting as appendicitis. CONCLUSIONS: Appendicitis can be a rare manifestation
      of CMV-IRIS in HIV-infected patients who start antiretroviral therapy. Evaluation
      of appendiceal tissue for cytopathic changes and CMV should be considered in
      acute appendicitis in HIV infected persons.

PMID- 24910268
TI  - Ecological generalism and behavioural innovation in birds: technical intelligence
      or the simple incorporation of new foods?
AB  - Generalist species are more successful than specialists in anthropogenically
      modified environments or in environments in which they have been introduced, but
      the nature of the link between generalism and establishment success is unclear. A
      higher feeding innovation rate has previously been reported in habitat generalist
      birds from North America. By allowing them to exploit new resources, this higher
      feeding innovation rate might explain the generalists' advantage. This result
      might be due to generalists being more likely to find new resources because they
      are exposed to more diverse environmental conditions. Alternatively, they might
      differ from specialists in other traits, in particular cognitive skills that
      might allow them to innovate more complex food searching and handling techniques.
      To test these hypotheses, we separated avian feeding innovations into a
      'technical' (novel searching and handling behaviour) and a 'food type'
      (incorporation of a new food in a species' diet) category. Technical innovations,
      but not food type innovations, have previously been shown to correlate with avian
      brain size, suggesting they reflect cognitive ability. We used a world-wide data
      base of 2339 feeding innovations recorded in the literature, covering a total of
      765 avian species and assessed the correlations between brain size and feeding
      innovation rates on one side and habitat and diet generalism on the other.
      Habitat generalism was positively related with food type innovation rate, but not
      technical innovation rate or brain size. This suggests that habitat generalist
      species are more likely to incorporate new food types in their diet because of
      higher chances to find new food resources in their environment, or of a higher
      opportunism, but not enhanced cognitive skills. In contrast, diet generalist
      species had higher food type and technical innovation rates, as well as larger
      brains, suggesting that cognitive skills might help species expand their diet
      breadth or that an increase in diet breadth might favour the evolution of
      enhanced cognitive abilities. Our results provide new insights into the nature of
      the generalists' advantage in the face of environmental changes, and suggest that
      dietary and habitat generalism are different, but convergent, routes to feeding
      flexibility and adaptation to changed environments. 

PMID- 24910269
TI  - Aging in a polluted world.

PMID- 24910270
TI  - A double-blind vehicle-controlled study of a preparation containing undecylenoyl
      phenylalanine 2% in the treatment of melasma in females.
AB  - BACKGROUND: Undecylenoyl phenylalanine is a novel skin-lightening agent, probably
      acting as alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-adrenergic
      receptor (beta-ADR) antagonist. OBJECTIVES: The objective of this double-blind
      randomized comparative study was to evaluate the efficacy and safety of a
      preparation containing undecylenoyl phenylalanine 2% in the topical treatment of
      melasma in females. METHODS: Forty female patients with melasma were randomly
      assigned to apply either the active preparation or the vehicle alone, twice daily
      for 12 weeks. Patients were evaluated monthly for efficacy and safety. RESULTS:
      In all, 37 patients completed the study. Of the 20 patients on active treatment,
      no one responded completely, but 17 (85%) had partial response. Of them, 11 had
      moderate improvement and six had marked improvement. Lightening of the lesions
      was evident from the first follow-up visit at 4 weeks. A statistically
      significant difference (P < 0.001) in efficacy between the active preparation and
      the vehicle was documented. Using patient assessment ratings, 80% were extremely
      satisfied or satisfied with the result. The reported side effects were minor and
      included erythema and itching or burning at the site of application. CONCLUSIONS:
      Undecylenoyl phenylalanine 2% achieved a significant lightening of melasma
      lesions with minimal side effects.

PMID- 24910271
TI  - A randomized comparison of the efficacy of low volume deep placement cheek
      injection vs. mid- to deep dermal nasolabial fold injection technique for the
      correction of nasolabial folds.
AB  - BACKGROUND: Hyaluronic acid (HA) fillers are FDA approved for improving the
      appearance of the nasolabial folds. Previous reports on the use of HA for this
      treatment have focused on injections directly into the location of the desired
      correction. To our knowledge, a study has not been done evaluating the efficacy
      of injecting a low volume of HA into the adjacent area of volume loss to correct
      both volume loss and adjacent lines. OBJECTIVE: The objective of this study was
      to compare the effectiveness and safety of three HA injection protocols including
      deep dermal cheek injection, mid- to deep dermal local nasolabial fold injection,
      and both injections for the correction of nasolabial folds. METHODS: This was a
      split-face, randomized study evaluating the use of three injection techniques -
      (i) deep bolus injection into the mid- to lateral cheek, (ii) local mid- to deep
      dermal injection into the nasolabial fold, and (iii) both deep injection into the
      mid- to lateral cheek and local mid- to deep dermal injection into the nasolabial
      fold - for the treatment of moderate to severe nasolabial folds. Wrinkle severity
      and Global Aesthetic Improvement Scales were measured before and 4-6 weeks after
      treatment as assessed by a blinded investigator. RESULTS: Patient and physician
      observations showed improvement both globally and in wrinkle severity score with
      each technique used with no statistical difference between techniques. Patients
      showed a slight preference for injection to both the mid- to lateral cheek and
      nasolabial fold, which was associated with the greatest amount of filler product
      administered. No serious adverse events were reported. CONCLUSION: Injection of a
      dermal filler, at low volumes, into either the nasolabial fold or mid- to lateral
      cheek results in similar improvement to the correction of the nasolabial folds.

PMID- 24910272
TI  - DNA photoprotection conveyed by sunscreen.
AB  - INTRODUCTION: Skin photoaging is the consequence of solar UV exposure, and DNA
      damage is an important part of this process. The objective of the current work
      was to demonstrate that in vitro skin models can be utilized to confirm that DNA
      damage protection is provided by sunscreens. METHODS: Skin equivalents were
      exposed to full-spectrum UV light administered with a standard research solar
      simulator with and without pre-application of sunscreen. Cyclopyrimidine dimer
      (CPD) and sunburn cell (SBC) formation as well as CPD quantitation were evaluated
      to determine DNA damage protection provided by the sunscreen. RESULTS: Marked
      decreases in both CPDs and SBCs were observed when sunscreen was applied prior to
      UV exposure. CONCLUSIONS: Sunscreen application prior to full-spectrum solar UV
      exposure protects DNA from photodamage measured by CPD and SBC formation. This
      can be expected to lessen the risk of photoaging and malignant transformation.

PMID- 24910273
TI  - Significant improvement in mild acne following a twice daily application for 6
      weeks of an acidic cleansing product (pH 4).
AB  - BACKGROUND: Cleansing products for acne should remove excessive sebum, reduce
      acne-related bacteria and improve inflammation. AIMS: The aim of the study was to
      investigate a topical cleansing product containing glycolic acid with pH 4 in
      mild acne vulgaris. METHODS: Sixty patients were recruited for this open
      uncontrolled clinical trial. The tested product was exclusively applied twice a
      day for 6 weeks. The efficacy was judged by a dermatologist according to the
      Leeds score after 3 and 6 weeks. In addition, efficacy and tolerability were
      judged subjectively by physician and patients. RESULTS: Mild acne improved
      significantly after 6 weeks (baseline: 0.699 vs. day 42: 0.602; P < 0.001).
      Efficacy and tolerability were judged better by physician as compared with
      patients' assessment. CONCLUSION: In this clinical trial, a topical cleansing
      product containing glycolic acid with pH 4 improved mild acne significantly
      following twice-daily application for 6 weeks as monotherapy.

PMID- 24910274
TI  - Combination of intense pulsed light, Sculptra, and Ultherapy for treatment of the
      aging face.
AB  - INTRODUCTION: Facial aging is a gradual process that involves a complex
      interaction of multiple factors including cutaneous photodamage and laxity,
      subcutaneous tissue volume loss, and bony resorption. These features have all
      been show to significantly improve with intense pulsed light (IPL), microfocused
      ultrasound (MFUS, Ultherapy), and poly-L-lactic acid (PLLA). METHODS: To review
      the use of IPL, MFUS, and PLLA in combination with the treatment of facial aging.
      RESULTS: Despite their extensive individual safety record, there is little data
      regarding combination therapy with these minimally invasive modalities.
      CONCLUSIONS: IPL, MFUS, and PLLA may be safely performed in a single treatment
      session to target multiple tissue planes concurrently without increased adverse
      events.

PMID- 24910275
TI  - An evaluation of the patient population for aesthetic treatments targeting
      abdominal subcutaneous adipose tissue.
AB  - A large and growing population of patients currently seeks minimally invasive
      therapeutic options for the aesthetic treatment of localized, central abdominal
      subcutaneous adipose tissue (SAT). We sought to evaluate the ideal population for
      aesthetic treatment of central abdominal SAT, highlight the existing disparities
      between SAT in obese (body mass index [BMI] >= 30; BMI) and nonobese (BMI < 30)
      patients, and review the available FDA-cleared, minimally invasive treatment
      options for central abdominal adiposity. The cosmetic issue of localized, central
      (periumbilical) abdominal adiposity in nonobese individuals is quite distinct
      from abdominal bulging secondary to obesity. Given the recognized clinical and
      physiologic differences between obese and nonobese counterparts, the exclusion of
      obese patients from clinical study by currently available FDA-cleared devices
      targeting abdominal fat, and the status of obesity as a chronic, systemic disease
      requiring medical, surgical, and/or lifestyle-altering therapies, minimally
      invasive therapeutic options for aesthetic reductions in central abdominal SAT
      must be limited to the nonobese population. 

PMID- 24910276
TI  - A prospective, open-label, multicenter, observational, postmarket study of the
      use of a 15 mg/mL hyaluronic acid dermal filler in the lips.
AB  - Hyaluronic acid (HA)-based injectable fillers three-dimensionally restore the
      natural contours of the lips and perioral area, thereby reducing some signs of
      aging lips. To evaluate the short-term aesthetic impact of treatment with the HA
      dermal filler Juvederm((r)) VOLBELLA((r)) with Lidocaine, formulated utilizing
      VYCROSS(TM) technology, for enhancement or correction of asymmetry of the lips,
      evaluated using a patient-centric approach. Sixty-two subjects were enrolled in
      this study, conducted at two sites in Germany. Primary endpoints were
      satisfaction with improvement, look and feel of the lips, assessed by subject and
      physician at first visit and 4 weeks post-treatment. Immediately after injection
      at first visit, 83.6% of subjects were Extremely Satisfied, Very Satisfied or
      Satisfied with improvement in the lips, which increased to 94.1% and 93.0% of
      subjects with/without top-up treatment at follow-up, respectively. After
      injection at first visit, 61.7% of subjects rated the look and feel of their lips
      as Extremely Natural or Very Natural, which increased to 75.0% and 93.0% of
      subjects with/without top-up treatment, respectively. The HA dermal filler was
      associated with minimal discomfort, bruising or swelling of the lips; almost two
      thirds of subjects (62%) returned to social engagements on the same day. The high
      degree of subject satisfaction with aesthetic improvement in the lips, as well as
      the natural look and feel, indicates that this HA dermal filler represents an
      effective treatment option for patients requiring lip enhancement. 

PMID- 24910277
TI  - Multipoint and multilevel injection technique of botulinum toxin A in facial
      aesthetics.
AB  - Botulinum toxin represents one of the most frequently requested cosmetic
      procedures. We treated 223 patients with facial wrinkles using a new technique of
      injection of botulinum toxin A (BTA) called multipoint and multilevel injection
      technique (MMIT). The aim of MMIT was to relax the muscle and not paralyze it.
      Patient satisfaction was evaluated by Facial Line Treatment Satisfaction
      Questionnaire (FTSQ). Treatment with botulinum toxin determined a good response
      in all patients. Facial rhytids were completely resolved in case of young skin
      and well reduced in case of aged skin, leaving a natural aspect both in static
      and dynamic wrinkles. Patient mean overall satisfaction evaluated with FTSQ was
      6.4 +/- 1.1. In our experience, the use of botulin toxin by MMIT consents a
      better calibration of action with a soft and natural result. This can be achieved
      by distributing the BTA dose through various injection points for each area
      ("multipoint injections"). Furthermore, injections can be performed at different
      levels ("multilevel injections"). The level of injections regulates the potency
      of effect on the muscle: if the level is deep (intramuscular), the effect will be
      strong while if it is medium or superficial (subcutaneous and intradermal), the
      effect will be soft. This consents a fine calibration of action on muscle
      activity with a personal aesthetic result. 

PMID- 24910278
TI  - Remodeling of periorbital, temporal, glabellar, and crow's feet areas with
      hyaluronic acid and botulinum toxin.
AB  - Botulinum toxins are currently used to reduce facial muscle activity, and
      hyaluronic acid is used to correct volume loss. This study evaluates the
      combination of abobotulinumtoxinA (Dysport) and hyaluronic acid 20 mg/mL
      (Perlane) for rejuvenating specific areas of the upper face. Subjects (n = 20)
      with mild to moderate temporal volume loss as well as glabellar and/or
      periorbital rhytids were enrolled in this single-center, open-label,
      nonrandomized pilot study. Subjects were randomly assigned a number and treated
      with hyaluronic acid, divided between temporal and glabellar region, and
      abobotulinumtoxinA in the periorbital and glabellar region. A 1-month touch-up
      was given if needed. Subjects were evaluated by the investigator, and each
      subject completed a questionnaire at baseline and at 3, 6, and 9 months after
      treatment. For glabellar lines and crow's feet, median grades decreased from
      baseline at 1 month and at 3 months, but returned to baseline values at 6 months.
      For temporal assessments, the median grade decreased from baseline at 1, 3, and 6
      months and returned to baseline at 9 months. Similar trends were observed in
      subjects' perceived age, perceived social and professional limitations, and
      desire to alter their facial appearance. Among subjects previously treated with
      botulinum toxin alone, 64% rated the combination treatment said "superior."
      Adverse effects were mild and transient. The combination of abobotulinumtoxinA
      and hyaluronic acid appears to rejuvenate the periorbital, temporal, glabellar,
      and crow's feet areas with minimal adverse effects. 

PMID- 24910279
TI  - Protective effect of red orange extract supplementation against UV-induced skin
      damages: photoaging and solar lentigines.
AB  - BACKGROUND: Exposure of the skin to solar ultraviolet (UV) radiations causes
      important oxidative damages that result in clinical and hystopathological
      changes, contributing to premature skin aging. Hyperpigmented lesions, also known
      as age spots, are one of the most visible alterations in skin photoaging. Skin is
      naturally equipped with antioxidant systems against UV-induced ROS generation;
      however, these antioxidant defenses are not completely efficient during exposure
      to sunlight. Oral antioxidants are able to counteract the harmful effects of UV
      radiation and to strengthen the physiological skin antioxidant defenses. AIMS:
      The present study was performed to evaluate the in vivo skin photo-protecting and
      anti-aging effects of a red orange (Citrus sinensis varieties Moro, Tarocco and
      Sanguinello) extract supplementation. Previous studies showed that red orange
      extracts possess strong in vitro free radical scavenging/antioxidant activity and
      photo-protective effects on human skin. MATERIALS/METHODS: The photo-protective
      effects of red orange extract intake against UV-induced skin erythema and melanin
      production in solar lentigo was evaluated on healthy volunteers by an objective
      instrumental method (reflectance spectrophotometry). RESULTS: Data obtained from
      in vivo studies showed that supplementation of red orange extract (100 mg/daily)
      for 15 days brought a significant reduction in the UV-induced skin erythema
      degree. Moreover, skin age spots pigmentation (melanin content) decreased from
      27% to 7% when subjects were exposed to solar lamp during red orange extract
      supplementation. CONCLUSIONS: Red orange extract intake can strengthen
      physiological antioxidant skin defenses, protecting skin from the damaging
      processes involved in photo-aging and leading to an improvement in skin
      appearance and pigmentation.

PMID- 24910280
TI  - Objective assessment of facial skin aging and the associated environmental
      factors in Japanese monozygotic twins.
AB  - Twin studies, especially those involving monozygotic (MZ) twins, facilitate the
      analysis of factors affecting skin aging while controlling for age, gender, and
      genetic susceptibility. The purpose of this study was to objectively assess
      various features of facial skin and analyze the effects of environmental factors
      on these features in MZ twins. At the Osaka Twin Research Center, 67 pairs of MZ
      twins underwent medical interviews and photographic assessments, using the
      VISIA((r)) Complexion Analysis System. First, the average scores of the right and
      left cheek skin spots, wrinkles, pores, texture, and erythema were calculated;
      the differences between the scores were then compared in each pair of twins.
      Next, using the results of medical interviews and VISIA data, we investigated the
      effects of environmental factors on skin aging. The data were analyzed using
      Pearson's correlation coefficient test and the Wilcoxon signed-rank test. The
      intrapair differences in facial texture scores significantly increased as the age
      of the twins increased (P = 0.03). Among the twin pairs who provided answers to
      the questions regarding history differences in medical interviews, the twins who
      smoked or did not use skin protection showed significantly higher facial texture
      or wrinkle scores compared with the twins not exposed to cigarettes or
      protectants (P = 0.04 and 0.03, respectively). The study demonstrated that skin
      aging among Japanese MZ twins, especially in terms of facial texture, was
      significantly influenced by environmental factors. In addition, smoking and skin
      protectant use were important environmental factors influencing skin aging. 

PMID- 24910281
TI  - Methods and results for small area estimation using smoking data from the 2008
      National Health Interview Survey.
AB  - The National Health Interview Survey, conducted by the National Center for Health
      Statistics, is designed to provide reliable design-based estimates for a wide
      range of health-related variables for national and four major geographical
      regions of the USA. However, state-level or substate-level estimates are likely
      to be unreliable because they are based on small sample sizes. In this paper, we
      compare the efficiency of different area-level models in estimating smoking
      prevalence for the 50 US states and the District of Columbia. Our study is based
      on survey data from the 2008 National Health Interview Survey in conjunction with
      a number of potentially related auxiliary variables obtained from the American
      Community Survey, an ongoing large complex survey conducted by the US Census. A
      major portion of this study is devoted to the investigation of several methods
      for estimating survey sampling variances needed to implement an area-level
      hierarchical model. Based on our findings, a hierarchical Bayesian method that
      uses a survey-adjusted random sampling variance model to capture the complex
      survey sampling variability appears to be somewhat superior to the other
      considered area-level models in accounting for small sample behavior of estimated
      survey sampling variances. Several diagnostic procedures are presented to compare
      the proposed methods.

PMID- 24910283
TI  - Novel neuroendocrine and metabolic mechanism provides the patented platform for
      important rejuvenation therapies: targeted therapy of telomere attrition and
      lifestyle changes of telomerase activity with the timing of neuron-specific
      imidazole-containing dipeptide-dominant pharmaconutrition provision.
AB  - Telomere length is emerging as a biomarker for aging and survival is paternally
      inherited and associated with parental lifespan. Telomere-associated cellular
      senescence may contribute to certain age-related disorders, including an increase
      in cancer incidence, wrinkling and diminished skin elasticity, atherosclerosis,
      osteoporosis, weight loss, age-related cataract, glaucoma and others. Shorter
      telomere length in leukocytes was associated cross-sectionally with
      cardiovascular disorders and its risk factors, including pulse pressure and
      vascular aging, obesity, vascular dementia, diabetes, coronary artery disease,
      myocardial infarction (although not in all studies), cellular turnover and
      exposure to oxidative and inflammatory damage in chronic obstructive pulmonary
      disease. Effective regulation of abnormal therapeutic targets of an age-related
      disease requires the alteration of either the topological structure or dynamic
      characteristics of telomeres which are DNA-protein structures at the ends of
      eukaryotic chromosomes, the DNA of which comprise noncoding repeats of guanine
      rich sequences. Telomeric DNA plays a fundamental role in protecting the cell
      from recombination and degradation, including those as the metabolic super
      achievers in the body, organ systems in a given target network of a disease and
      aging. In order to manage and control the complex direct and indirect target
      hubs, in this paper, a review of the recent patents is made analyzing techniques,
      new approaches developed during the last years in adaptive pharmacology directed
      at slowing and preventing the loss of telomere length that may slow aging using
      pharmaceutical and nutritional module-based designs, such as with regard to the
      timing of administration of imidazole-containing dipeptides. We discuss our
      recent identification of the role of neuron-specific imidazole- containing
      dipeptide based compounds (L-carnosine, N-acetylcarnosine, carcinine) that
      regulate and therapeutically control telomere shortening, telomerase activity and
      cellular senescence. We support a therapeutic concept of using nonhydrolyzed
      forms of naturally occurring imidazole-dipeptide based compounds carnosine and
      carcinine, making it clinically possible that slowing down the rate of telomere
      shortening could slow down the human aging process in specific tissues where
      proliferative senescence is known to occur with the demonstrated evidence of
      telomere shortening appeared to be a hallmark of oxidative stress and disease.
      The preliminary longitudinal studies of elderly individuals suggest that longer
      telomeres are associated with better survival and an advanced oral
      pharmaconutrition provision with non-hydrolyzed carnosine (or carcinine and
      patented compositions thereof) is a useful therapeutic tool of a critical
      telomere length maintenance (allowing indirectly to manipulate with telomerase
      activity) that may fundamentally be applied in the therapeutic treatment of
      agerelated sight-threatening eye disorders, Diabetes mellitus, sarcopenia (that
      is the gradual loss of muscle mass) that can affect elderly people and subjects
      under the effect of exhausting exercises and physical load, prolong life
      expectancy, increase survival and chronological age of an organism in health
      control, smoking behavior, metabolic syndrome increasing the risk of developing
      cardio-vascular diseases, age-related neurodegenerative diseases, including
      Alzheimer's disease and cognitive impairment. 

PMID- 24910284
TI  - Increasing ambulatory surgery potential by non-medicalized accommodation: matched
      comparison of the 2011 national hospital activity data to 66 local stays.
AB  - INTRODUCTION: Several policy and cultural factors still hinder the development of
      ambulatory surgery (AS) in France. Our surgery unit developed a day-surgery
      approach with extension of a non-medicalized post-operative stay in a hotel-like
      structure within the hospital, called an "ambulotel". The present study aims to
      evaluate the potential of this approach in increasing the possibilities of
      ambulatory surgery by comparing our stays to those of a nationwide database.
      PATIENTS AND METHODS: We matched 66 patients according to seven criteria in our
      one-day ambulotel program to the 2011 DRG national database and then compared
      their characteristics. RESULTS: Of the 10,428 patients in the database with one
      night stays in a traditional surgery unit, more than half (52%) would probably
      have been eligible for ambulatory surgery with a potential theoretical savings
      estimated at ?12,806,568. CONCLUSION: This estimated amount of savings represents
      a major medical and economic issue. The savings could contribute to increased
      ambulatory surgery activity in France by creating new dedicated Ambulatory Units,
      pooling conventional beds, or using night accommodation in non-hospital nursing
      homes, for example.

PMID- 24910282
TI  - A role for the lateral dorsal tegmentum in memory and decision neural circuitry.
AB  - A role for the hippocampus in memory is clear, although the mechanism for its
      contribution remains a matter of debate. Converging evidence suggests that
      hippocampus evaluates the extent to which context-defining features of events
      occur as expected. The consequence of mismatches, or prediction error, signals
      from hippocampus is discussed in terms of its impact on neural circuitry that
      evaluates the significance of prediction errors: Ventral tegmental area (VTA)
      dopamine cells burst fire to rewards or cues that predict rewards (Schultz,
      Dayan, & Montague, 1997). Although the lateral dorsal tegmentum (LDTg)
      importantly controls dopamine cell burst firing (Lodge & Grace, 2006) the
      behavioral significance of the LDTg control is not known. Therefore, we evaluated
      LDTg functional activity as rats performed a spatial memory task that generates
      task-dependent reward codes in VTA (Jo, Lee, & Mizumori, 2013; Puryear, Kim, &
      Mizumori, 2010) and another VTA afferent, the pedunculopontine nucleus (PPTg,
      Norton, Jo, Clark, Taylor, & Mizumori, 2011). Reversible inactivation of the LDTg
      significantly impaired choice accuracy. LDTg neurons coded primarily egocentric
      information in the form of movement velocity, turning behaviors, and behaviors
      leading up to expected reward locations. A subset of the velocity-tuned LDTg
      cells also showed high frequency bursts shortly before or after reward
      encounters, after which they showed tonic elevated firing during consumption of
      small, but not large, rewards. Cells that fired before reward encounters showed
      stronger correlations with velocity as rats moved toward, rather than away from,
      rewarded sites. LDTg neural activity was more strongly regulated by egocentric
      behaviors than that observed for PPTg or VTA cells that were recorded by Puryear
      et al. and Norton et al. While PPTg activity was uniquely sensitive to ongoing
      sensory input, all three regions encoded reward magnitude (although in different
      ways), reward expectation, and reward encounters. Only VTA encoded reward
      prediction errors. LDTg may inform VTA about learned goal-directed movement that
      reflects the current motivational state, and this in turn may guide VTA
      determination of expected subjective goal values. When combined it is clear the
      LDTg and PPTg provide only a portion of the information that dopamine cells need
      to assess the value of prediction errors, a process that is essential to future
      adaptive decisions and switches of cognitive (i.e. memorial) strategies and
      behavioral responses. 

PMID- 24910285
TI  - Biointegration of corneal macroporous membranes based on poly(ethyl acrylate)
      copolymers in an experimental animal model.
AB  - Currently available keratoprosthesis models (nonbiological corneal substitutes)
      have a less than 75% graft survival rate at 2 years. We aimed at developing a
      model for keratoprosthesis based on the use of poly(ethyl acrylate) (PEA)-based
      copolymers, extracellular matrix-protein coating and colonization with adipose
      derived mesenchymal stem cells. Human adipose tissue derived mesenchymal stem
      cells (h-ADASC) colonization efficiency of seven PEA-based copolymers in
      combination with four extracellular matrix coatings were evaluated in vitro.
      Then, macroporous membranes composed of the optimal PEA subtypes and coating
      proteins were implanted inside rabbit cornea. After a 3-month follow-up, the
      animals were euthanized, and the clinical and histological biointegration of the
      implanted material were assessed. h-ADASC adhered and survived when cultured in
      all PEA-based macroporous membranes. The addition of high hydrophilicity to PEA
      membranes decreased h-ADASC colonization in vitro. PEA-based copolymer containing
      10% hydroxyethyl acrylate (PEA-HEA10) or 10% acrylic acid (PEA-AAc10) monomeric
      units showed the best cellular colonization rates. Collagen plus keratan sulfate
      coated polymers demonstrated enhanced cellular colonization respect to
      fibronectin, collagen, or uncoated PEAs. In vivo implantation of membranes
      resulted in an extrusion rate of 72% for PEA, 50% for PEA-AAc10, but remarkably
      of 0% for PEA-HEA10. h-ADASC survival was demonstrated in all the membranes after
      3 months follow-up. A slight reduction in the extrusion rate of h-ADASC colonized
      materials was observed. No significant differences between the groups with and
      without h-ADASC were detected respect to transparency or neovascularization. We
      propose PEA with low hydroxylation as a scaffold for the anchoring ring of future
      keratoprosthesis.

PMID- 24910286
TI  - Interpretation of HbA1c : association with mean cell volume and haemoglobin
      concentration.
AB  - AIM: The utility of HbA1c in diabetes diagnosis is reduced in settings associated
      with altered haemoglobin glycation. We have studied whether HbA1c varies with
      mean cell volume and mean cell haemoglobin concentration as measures of
      haemoglobin metabolism. METHODS: Randomly selected adults from rural Victoria,
      Australia, were invited for biomedical assessment. After excluding patients with
      known diabetes and/or serum creatinine >= 0.12 mmol/l, 1315 adults were included.
      Demography, arthropometric measurements, oral glucose tolerance test, analyses of
      full blood count and HbA1c were undertaken. RESULTS: After adjusting for age,
      sex, ethnicity, BMI, town and socio-economic status, there were no significant
      differences in haemoglobin, mean cell volume or mean cell haemoglobin
      concentration by glycaemic status (defined by oral glucose tolerance test). HbA1c
      was significantly and independently associated with fasting glucose, town, mean
      cell haemoglobin concentration, ethnicity, age and BMI among men < 50 years (R2 =
      33.8%); fasting glucose, 2-h glucose, mean cell haemoglobin concentration and
      town among men >= 50 years (R2 = 47.9%); fasting glucose, mean cell volume, mean
      cell haemoglobin concentration, town, 2-h glucose and age among women < 50 years
      (R2 = 46.3%); fasting glucose, mean cell haemoglobin concentration, mean cell
      volume and 2-h glucose among women >= 50 years (R2 = 51.6%). A generalized linear
      model showed a gradient from an adjusted mean HbA1c of 36 (95% CI 34-38) mmol/mol
      with a mean cell haemoglobin concentration of <= 320 g/l to 30 (95% CI 29-31)
      mmol/mol with a mean cell haemoglobin concentration of > 370 g/l. The gradient
      across mean cell volume was negative, but only by 1 mmol/mol (0.1%) HbA1c .
      CONCLUSION: A mean HbA1c difference of 5 mmol/mol (0.5%) across the mean cell
      haemoglobin concentration reference range suggests that an accompanying full
      blood count examination may be required for its use in the diagnosis of diabetes.
      Further studies are required to confirm this.

PMID- 24910287
TI  - A thixotropic supramolecular hydrogel of adenine and riboflavin-5'-phosphate
      sodium salt showing enhanced fluorescence properties.
AB  - An equimolar mixture of riboflavin-5'-phosphate sodium salt (RP) and adenine (AD)
      dissolved in a phosphate buffer (pH 4.0, 1.0% w/v) produces a red coloured
      transparent thixotropic hydrogel at 30  degrees C. The gelation of the RPAD
      system occurs in the pH range of 2-5. FTIR spectra and WAXS patterns indicate
      self-assembly via H-bonding between the >C=O group of RP and the amino/imino
      group of AD followed by supramolecular organization through a pi-stacking process
      producing a fibrillar network structure. FESEM images clearly indicate that the
      nanofibres are produced from the intertwining of helical fibrils. The dynamic
      frequency sweep experiment of the supramolecular gel at a constant strain of 1%
      exhibits a wide linear viscoelastic region and a considerably higher G' value
      (460 Pa) than that of G'' (21 Pa) confirming the gel nature of the RPAD system.
      The hydrogel shows high stiffness (G'/G'' = 3.3), a high yield stress (sigma*)
      (79.5 Pa) and a moderate critical strain (gamma = 17.5%). Time sweep experiments
      at both low (0.1%) and high strain (100%) indicate the thixotropic property of
      the gel. The RPAD hydrogel shows non-Newtonian viscosity in the shear rate region
      (0.1-158 s(-1)) and after that there is a sudden fall of viscosity. The gel
      melting point obtained by the falling ball method is 6 degrees  higher than that
      obtained by the DSC method probably due to the presence of the thixotropic
      property of the gel. The UV-vis spectra indicate a red shift of the pi-pi*
      transition band of RP in the RPAD xerogel. On excitation of the RPAD hydrogel at
      373 nm it shows twelve times enhancement of emission intensity with a 7 nm red
      shift of the emission peak. This has been attributed to the enhancement of
      lifetime from 2.2 ns in RP to 3.4 ns in the RPAD hydrogel. With increase of
      temperature, the fluorescence intensity of the RPAD hydrogel at first increases
      till 40  degrees C, then decreases up to 55  degrees C and it again increases
      after 60  degrees C.

PMID- 24910288
TI  - [Salvage cryotherapy for recurrent prostate cancer after radiotherapy failure:
      principles, indications, patient selection, oncological results and morbidity].
AB  - Potentially curative salvage options for biochemical failure after primary
      prostatic radiotherapy include salvage radical prostatectomy, brachytherapy, high
      intensity focused ultrasound and cryotherapy. Salvage cryoablation for recurrent
      prostate cancer after irradiation failure is currently a well-established
      therapeutic option, since technical improvements have permitted better oncologic
      outcomes and lower complications rates over the years. This article reviews
      surgical technique, oncologic and functional outcomes, as well as morbidity and
      complications of salvage cryotherapy for local recurrence after external beam
      radiotherapy or brachytherapy for prostate cancer. 

PMID- 24910289
TI  - Obesity paradox not observed among patients with angiographically proved coronary
      artery disease in southern China.

PMID- 24910290
TI  - Genetic and environmental risk for major depression in African-American and
      European-American women.
AB  - It is unknown whether there are racial differences in the heritability of major
      depressive disorder (MDD) because most psychiatric genetic studies have been
      conducted in samples comprised largely of white non-Hispanics. To examine
      potential differences between African-American (AA) and European-American (EA)
      young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders,
      4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2)
      genetic and/or environmental liability to MDD, we analyzed data from a large
      population-representative sample of twins ascertained from birth records (n = 550
      AA and n = 3226 EA female twins) aged 18-28 years at the time of MDD assessment
      by semi-structured psychiatric interview. AA women were more likely to have MDD
      risk factors; however, there were no significant differences in lifetime MDD
      prevalence between AA and EA women after adjusting for covariates (odds ratio =
      0.88, 95% confidence interval [CI]: 0.67-1.15). Most MDD risk factors identified
      among AA women were also associated with MDD at similar magnitudes among EA
      women. Although the MDD heritability point estimate was higher among AA women
      than EA women in a model with paths estimated separately by race (56%, 95% CI: 29
      78% vs. 41%, 95% CI: 29-52%), the best fitting model was one in which additive
      genetic and non-shared environmental paths for AA and EA women were constrained
      to be equal (A = 43%, 33-53% and E = 57%, 47-67%). In spite of a marked elevation
      in the prevalence of environmental risk exposures related to MDD among AA women,
      there were no significant differences in lifetime prevalence or heritability of
      MDD between AA and EA young women. 

PMID- 24910291
TI  - Avoiding research waste through cost-effectiveness analysis: the example of
      medication adherence-enhancing interventions.
AB  - Cost-effectiveness analysis (CEA) in health care has two important goals. One is
      to inform current funding decisions and the other is to inform future research.
      In the current literature, however, the first goal seems to play a much larger
      role than the second. The purpose of this note is to show, using the example of
      medication adherence-enhancing interventions, that CEA can play an important role
      in informing future clinical trials. In this example incremental cost
      effectiveness ratios of drug treatment larger than zero generally prohibit the
      conduct of clinical trials on the efficacy/effectiveness of adherence-enhancing
      interventions. Current evidence suggests, however, that CEAs on drug treatment
      are rarely conducted before running such trials. 

PMID- 24910292
TI  - Testing the psychometric properties of the Cognitions Checklist, a measure to
      differentiate anxiety and depression among older adults.
AB  - Considerable debate has been waged in the field about whether anxiety and
      depressive cognitions can be discriminated, and whether they can discriminate
      anxiety and depression symptoms. The current study examined a standard measure of
      cognitions, the Cognitions Checklist (CCL) that has yielded mixed results when
      tested in older age samples. A community sample of older adults (N=169; mean
      age=75.70; SD=8.55) completed a series of self-report questionnaires, including
      the CCL as well as measures of anxiety and depression symptoms. The CCL, which
      yielded a three-factor structure rather than the typical two-factor structure,
      did not cognitively discriminate anxiety from depression. The results have
      implications for understanding cognitive factors that differentiate between
      anxiety and depression symptoms in older adults and suggest the importance of
      assessing cognitions that are tailored to the concerns of this population.

PMID- 24910293
TI  - Inlay-retained cantilever fixed dental prostheses to substitute a single
      premolar: impact of zirconia framework design after dynamic loading.
AB  - The purpose of this in-vitro study was to evaluate the influence of the framework
      design on the durability of inlay-retained cantilever fixed dental prostheses (IR
      FDPs), made from zirconia ceramic, after artificial ageing. Forty-eight caries
      free human premolars were prepared as abutments for all-ceramic cantilevered IR
      FDPs using six framework designs: occlusal-distal (OD) inlay, OD inlay with an
      oral retainer wing, OD inlay with two retainer wings, mesial-occlusal-distal
      (MOD) inlay, MOD inlay with an oral retainer ring, and veneer partial coping with
      a distal box (VB). Zirconia IR-FDPs were fabricated via computer-aided
      design/computer-aided manufacturing (CAD/CAM) technology. The bonding surfaces
      were air-abraded (50 MUm alumina/0.1 MPa), and the frameworks were bonded with
      adhesive resin cement. Specimens were stored for 150 d in a 37 degrees C water
      bath during which they were thermocycled between 5 and 55 degrees C for 37,500
      cycles; thereafter, they were exposed to 600,000 cycles of dynamic loading with a
      5-kg load in a chewing simulator. All surviving specimens were loaded onto the
      pontic and tested until failure using a universal testing machine. The mean
      failure load of the groups ranged from 260.8 to 746.7 N. Statistical analysis
      showed that both MOD groups exhibited significantly higher failure loads compared
      with the other groups (i.e. the three OD groups and the VB group) and that there
      was no significant difference in the failure load among the OD groups and the VB
      group. In conclusion, zirconia IR-FDPs with a modified design exhibited promising
      failure modes.

PMID- 24910294
TI  - Costimulatory TNFR family members in control of viral infection: outstanding
      questions.
AB  - Members of the TNFR family can play prominent roles in controlling the magnitude,
      duration and phenotype of the immune response to viruses. The importance of
      particular TNFRs in different viral infections and whether they contribute to
      viral control or pathology is dependent on the virus and the severity of the
      infection. TNFRs and their ligands are widely and differentially expressed on
      both adaptive and innate immune cell types. The cell types through which TNFRs
      exert their effects, the unique signals provided by each member of the family,
      and how these signals are ultimately integrated during an anti-viral immune
      response remain to be fully elucidated. Here we discuss the role of 4-1BB, OX40,
      CD27 and GITR and their ligands during viral infection and highlight some of the
      outstanding questions in the field. 

PMID- 24910295
TI  - Successful training of self-sufficient interventional paediatric cardiology team
      in a sub-Saharan setting: a multicentre collaborative model.
AB  - BACKGROUND: Most children in the Third World do not have access to treatment for
      heart diseases, as the priorities of health care are different from the developed
      countries. MATERIALS AND METHODS: Since 2009, teams supported by the Chain of
      Hope and Spanish medical volunteers have travelled twice a year to help develop
      paediatric cardiac services in the Cardiac Center in Ethiopia, undertaking four
      missions each year. As of December 2012, 296 procedures were performed on 287
      patients. The procedures included 128 duct occlusions, 55 pulmonary valve
      dilations, 25 atrial septal defect closures, 14 mitral valve dilations, and
      others. The local staff were trained to perform a majority of these cases.
      RESULTS: Procedural success was achieved in 264 (89.2%). There were three deaths,
      five device embolisations, and three complications in mitral valve dilation.
      During the visits, the local staff were trained including one cardiologist, six
      nurses, and two technicians. The local team performed percutaneous interventions
      on its own after a couple of years. The goal is also to enable the local team to
      perform interventions independently. CONCLUSION: Training of an interventional
      cardiology team in a sub-Saharan setting is challenging but achievable. It may be
      difficult for a single centre to commit to sending frequent missions to a
      developing country to make a meaningful contribution to the training of local
      teams. In our case, coordination between the teams from the two countries helped
      to achieve our goals.

PMID- 24910296
TI  - Treatment of refractory necrobiotic xanthogranulomas with extracorporeal
      photopheresis and intravenous immunoglobulin.
AB  - Necrobiotic xanthogranuloma (NXG) is a disease of fibrotic or telangiectatic
      granulomatous papules and nodules that can ultimately progress into ulcerated
      plaques. Although the exact cause of NXG is unknown, it most often occurs in
      patients with paraproteinemia secondary to a hematologic disease. Consequently,
      therapy for NXG is targeted at treating the underlying hematologic disease, and
      subsequent paraproteinemia, with alkylating agents, antimetabolites, radiation,
      and/or immunosuppressive agents. Cases refractory to these therapies often have
      poor outcomes. We report the successful treatment of two patients with refractory
      NXG with two different modalities: extracorporeal photopheresis (ECP) and
      intravenous immunoglobulin (IVIG). The first case shows a patient without
      paraproteinemia who had success with ECP and IVIG, and the second is a patient
      with paraproteinemia treated effectively with IVIG. The beneficial response of
      our patients to IVIG, as well as ECP, shows that they may be an effective
      treatment option for refractory NXG. 

PMID- 24910297
TI  - Reprint of: Enantiomeric separation of functionalized ethano-bridged Troger bases
      using macrocyclic cyclofructan and cyclodextrin chiral selectors in high
      performance liquid chromatography and capillary electrophoresis with application
      of principal component analysis.
AB  - The enantiomeric separation of a series of racemic functionalized ethano-bridged
      Troger base compounds was examined by high performance liquid chromatography
      (HPLC) and capillary electrophoresis (CE). Using HPLC and CE the entire set of 14
      derivatives was separated by chiral stationary phases (CSPs) and chiral additives
      composed of cyclodextrin (native and derivatized) and cyclofructan (derivatized).
      Baseline separations (Rs >= 1.5) in HPLC were achieved for 13 of the 14 compounds
      with resolution values as high as 5.0. CE produced 2 baseline separations. The
      separations on the cyclodextrin CSPs showed optimum results in the reversed phase
      mode, and the LARIHC cyclofructan CSPs separations showed optimum results in the
      normal phase mode. HPLC separation data of the compounds was analyzed using
      principal component analysis (PCA). The PCA biplot analysis showed that retention
      is governed by the size of the R1 substituent in the case of derivatized
      cyclofructan and cyclodextrin CSPs, and enantiomeric resolution closely
      correlated with the size of the R2 group in the case of non-derivatized gamma
      cyclodextrin CSP. It is clearly shown that chromatographic retention is necessary
      but not sufficient for the enantiomeric separations of these compounds.

PMID- 24910299
TI  - Kidney allograft function and histology in recipients dying with a functioning
      graft.
AB  - Death with function (DWF) is a major cause of kidney allograft failure. Allograft
      dysfunction may contribute to DWF. The aim of this study was to examine the
      relationship between DWF and allograft function using estimated GFR (eGFR) and
      histology. We retrospectively analyzed 1842 kidney allografts transplanted at our
      center from 1996 to 2010. eGFR was estimated using the MDRD equation. Biopsies
      obtained 12 months posttransplant and within 1 year of DWF were analyzed.
      Proportional hazards models were used to examine the relationship between eGFR
      and DWF. During 68 +/- 43 months of follow-up, 14% (n = 256) of recipients
      experienced DWF. Risk factors of DWF included increasing recipient age (hazard
      ratio [HR] = 2.07, confidence interval [CI] 1.77-2.43, p < 0.0001), diabetes (HR
      = 2.58, CI 1.81-3.69, p < 0.0001), prior dialysis (HR = 1.47, CI 1.05-2.06, p =
      0.03) and eGFR <40 mL/min/1.73 m(2) (HR 2.26 per 10 mL/min/1.73 m(2) decrease in
      eGFR, CI 1.82-2.81, p < 0.0001). Prior to death, only 15.9% (n = 39) of DWF
      recipients had stage 4 chronic kidney disease (CKD) and only 4.9% (n = 12) had
      stage 5 CKD. Most biopsies performed within 1 year of DWF (68%) demonstrated
      benign histology and were comparable to biopsies from matched controls. In
      conclusion, allograft dysfunction is independently associated with DWF. However,
      the majority of DWF recipients have well-preserved allograft function and
      histology prior to death. 

PMID- 24910298
TI  - A novel mouse model of endometriosis mimics human phenotype and reveals insights
      into the inflammatory contribution of shed endometrium.
AB  - Endometriosis is an estrogen-dependent inflammatory disorder characterized by the
      presence of endometrial tissue outside the uterine cavity. Patients experience
      chronic pelvic pain and infertility, with the most likely origin of the tissue
      deposits (lesions) being endometrial fragments shed at menses. Menstruation is an
      inflammatory process associated with a dramatic increase in inflammatory
      mediators and tissue-resident immune cells. In the present study, we developed
      and validated a mouse model of endometriosis using syngeneic menstrual
      endometrial tissue introduced into the peritoneum of immunocompetent mice. We
      demonstrate the establishment of endometriotic lesions that exhibit similarities
      to those recovered from patients undergoing laparoscopy. Specifically, in both
      cases, lesions had epithelial (cytokeratin(+)) and stromal (vimentin/CD10(+))
      cell compartments with a well-developed vasculature (CD31(+) endothelial cells).
      Expression of estrogen receptor beta was increased in lesions compared with the
      peritoneum or eutopic endometrium. By performing experiments using mice with
      green fluorescent protein-labeled macrophages (MacGreen) in reciprocal transfers
      with wild-type mice, we obtained evidence that macrophages present in the
      peritoneum and in menses endometrium can contribute to the inflammatory
      microenvironment of the lesions. In summary, we developed a mouse model of
      endometriosis that exhibits similarities to human peritoneal lesions with respect
      to estrogen receptor expression, inflammation, and macrophage infiltration,
      providing an opportunity for further studies and the possible identification of
      novel therapies for this perplexing disorder.

PMID- 24910300
TI  - Review of the impact of presbyopia on quality of life in the developing and
      developed world.
AB  - PURPOSE: To examine the public health impact of presbyopia regarding its effect
      on quality of life (QoL) and society in both the developed and developing worlds.
      METHODS: A database was created from articles found on PubMed, the Cochrane
      Library and Science Direct using the following search terms: presbyopia, QoL,
      accommodation, impact, cost, prevention, treatment and public health. Articles
      were accepted into the database if they addressed presbyopia and public health.
      RESULTS: This study showed in the developed world presbyopic subjects treated
      with reading glasses suffered a reduction in QoL parameters compared with those
      who were younger and emmetropic. A small minority of subjects were assessed to be
      a candidate for additional non-spectacle treatment measures. In undeveloped
      areas, the manifestations of presbyopia were similar to the developed world in
      symptoms, age and reduced QoL. However, there was inadequate treatment of this
      condition, even with reading glasses. The availability of reading glasses ranged
      from 6 to 45%. Activities of daily living could not be accomplished as easily
      without near correction of reading. Reasons described for the lack of correction
      included: lack of access to medical care, poor awareness of decreased near
      vision, lack of motivation and cost. Overall scant data exist regarding
      presbyopia and its impact and how treatment affects QoL. CONCLUSIONS: This review
      suggests that the effect of presbyopia and its treatments on QoL remain poorly
      described and incompletely treated, especially in developing areas of the world.

PMID- 24910301
TI  - RNA clamping by Vasa assembles a piRNA amplifier complex on transposon
      transcripts.
AB  - Germline-specific Piwi-interacting RNAs (piRNAs) protect animal genomes against
      transposons and are essential for fertility. piRNAs targeting active transposons
      are amplified by the ping-pong cycle, which couples Piwi endonucleolytic slicing
      of target RNAs to biogenesis of new piRNAs. Here, we describe the identification
      of a transient Amplifier complex that mediates biogenesis of secondary piRNAs in
      insect cells. Amplifier is nucleated by the DEAD box RNA helicase Vasa and
      contains the two Piwi proteins participating in the ping-pong loop, the Tudor
      protein Qin/Kumo and antisense piRNA guides. These components assemble on the
      surface of Vasa's helicase domain, which functions as an RNA clamp to anchor
      Amplifier onto transposon transcripts. We show that ATP-dependent RNP remodeling
      by Vasa facilitates transfer of 5' sliced piRNA precursors between ping-pong
      partners, and loss of this activity causes sterility in Drosophila. Our results
      reveal the molecular basis for the small RNA amplification that confers adaptive
      immunity against transposons. 

PMID- 24910303
TI  - Visualized analysis of cellular fatty acid profiles of Vibrio parahaemolyticus
      strains under cold stress.
AB  - Vibrio parahaemolyticus is a common foodborne bacterial pathogen, which survives
      in cold environments and is sometimes difficult to culture. Fatty acid analysis
      under cold stress was conducted for several V. parahaemolyticus strains using gas
      chromatography/mass spectrometry, and the results were compared with those of the
      controls. All the fatty acid profiles obtained were visualized by
      multidimensional scaling (MDS) and self-organized map (SOM). It was observed that
      the fatty acid profiles of V. parahaemolyticus substantially changed under cold
      stress. The percentage of methyl palmitate remarkably decreased and that of
      methyl palmitoleate (except for two strains) and methyl oleate increased. These
      findings demonstrate the role of fatty acids in cold stress. The changes in the
      fatty acid profiles illustrated by MDS and SOM could differentiate strains under
      cold stress from the controls and can potentially lead to a method of detecting
      injured cold-stressed V. parahaemolyticus.

PMID- 24910304
TI  - Mortality associated with systemic lupus erythematosus in France assessed by
      multiple-cause-of-death analysis.
AB  - OBJECTIVE: To assess the mortality profile of systemic lupus erythematosus (SLE)
      patients in France using multiple-cause-of-death analysis. METHODS: Data were
      collected between 2000 and 2009 in the French Epidemiological Center for the
      Medical Causes of Death database, and death certificates issued upon the death of
      an adult for whom SLE was an underlying cause of death (UCD) or a non-underlying
      cause of death (NUCD) were evaluated using multiple-cause-of-death analysis. Sex,
      age, sex ratio, standardized mortality rates, as well as frequency of the various
      causes of death were assessed, at both a national and a regional level. For the
      main causes of death, the observed number of deaths in relation to the expected
      number of deaths (O:E ratio) (standardized for age and sex) was calculated.
      RESULTS: During the study period, 1,593 deaths related to SLE were identified.
      The mean +/- SD age at death was 63.5 +/- 18.4 years and the sex ratio
      (female:male) was 3.5. The mean standardized mortality rate was 3.2 per 1 million
      people (range 2.7-4.1). When SLE was the UCD (n = 637), the main NUCDs were
      cardiovascular diseases (49.5%), infectious diseases (24.5%), and renal failure
      (23.2%). When SLE was an NUCD (n = 956), the most common UCDs were cardiovascular
      diseases (35.7%), neoplasms (13.9%), and infectious diseases (10.3%). The overall
      O:E ratio was >1 for infectious and cardiovascular diseases and renal failure
      (especially among people <40 years of age for the latter 2 causes), but was <1
      for neoplasms. CONCLUSION: Cardiovascular disease is the leading cause of death
      associated with SLE in France.

PMID- 24910305
TI  - Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact
      on the aging process.
AB  - Many aging theories have proposed that mitochondria and energy metabolism have a
      major role in the aging process. There are recent studies indicating that Krebs
      cycle intermediates can shape the epigenetic landscape of chromatin by regulating
      DNA and histone methylation. A growing evidence indicates that epigenetics plays
      an important role in the regulation of healthspan but also is involved in the
      aging process. 2-Oxoglutarate (alpha-ketoglutarate) is a key metabolite in the
      Krebs cycle but it is also an obligatory substrate for 2-oxoglutarate-dependent
      dioxygenases (2-OGDO). The 2-OGDO enzyme family includes the major enzymes of DNA
      and histone demethylation, i.e. Ten-Eleven Translocation (TETs) and Jumonji C
      domain containing (JmjC) demethylases. In addition, 2-OGDO members can regulate
      collagen synthesis and hypoxic responses in a non-epigenetical manner.
      Interestingly, succinate and fumarate, also Krebs cycle intermediates, are potent
      inhibitors of 2-OGDO enzymes, i.e. the balance of Krebs cycle reactions can
      affect the level of DNA and histone methylation and thus control gene expression.
      We will review the epigenetic mechanisms through which Krebs cycle intermediates
      control the DNA and histone methylation. We propose that age-related disturbances
      in the Krebs cycle function induce stochastic epigenetic changes in chromatin
      structures which in turn promote the aging process. 

PMID- 24910307
TI  - Encoding optical signals.
AB  - Light up tomorrow: A photochromic material with excellent fatigue resistance,
      high thermal stability, and quantitative photoswitching can be used as a linear
      photoswitching material to replace nonlinear optical materials for encoding
      optical signals. Therefore, information in one light ray can be directly
      transmitted to another light ray without converting back to the electronic
      format. 

PMID- 24910309
TI  - Assessment of energy potential from wetland plants along the minor channel
      network on an agricultural floodplain.
AB  - Renewable energy sources such as biomasses can play a pivotal role to ensure
      security of energy supply and reduce greenhouse gases through the substitution of
      fossil fuels. At present, bioenergy is mainly derived from cultivated crops that
      mirror the environmental impacts from the intensification of agricultural systems
      for food production. Instead, biomass from perennial herbaceous species growing
      in wetland ecosystems and marginal lands has recently aroused interest as
      bioenergy for electricity and heat, methane and 2nd-generation bioethanol. The
      aim of this paper is to assess, at local scale, the energy potential of wetland
      vegetation growing along the minor hydrographic network of a reclamation area in
      Northeast Italy, by performing energy scenarios for combustion, methane and 2nd
      generation ethanol. The research is based on a cross-methodology that combines
      survey analyses in the field with a GIS-based approach: the former consists of
      direct measurements and biomass sampling, the latter of spatial analyses and
      scaling up simulations at the minor channel network level. Results highlight that
      biomass from riparian zones could represent a significant source of bioenergy for
      combustion transformation, turning the disposal problem to cut and store in situ
      wetland vegetation into an opportunity to produce sustainable renewable energy at
      local scale. 

PMID- 24910306
TI  - Aging and longevity in the simplest animals and the quest for immortality.
AB  - Here we review the examples of great longevity and potential immortality in the
      earliest animal types and contrast and compare these to humans and other higher
      animals. We start by discussing aging in single-celled organisms such as yeast
      and ciliates, and the idea of the immortal cell clone. Then we describe how these
      cell clones could become organized into colonies of different cell types that
      lead to multicellular animal life. We survey aging and longevity in all of the
      basal metazoan groups including ctenophores (comb jellies), sponges, placozoans,
      cnidarians (hydras, jellyfish, corals and sea anemones) and myxozoans. Then we
      move to the simplest bilaterian animals (with a head, three body cell layers, and
      bilateral symmetry), the two phyla of flatworms. A key determinant of longevity
      and immortality in most of these simple animals is the large numbers of
      pluripotent stem cells that underlie the remarkable abilities of these animals to
      regenerate and rejuvenate themselves. Finally, we discuss briefly the evolution
      of the higher bilaterians and how longevity was reduced and immortality lost due
      to attainment of greater body complexity and cell cycle strategies that protect
      these complex organisms from developing tumors. We also briefly consider how the
      evolution of multiple aging-related mechanisms/pathways hinders our ability to
      understand and modify the aging process in higher organisms. 

PMID- 24910308
TI  - Simultaneous bioelectricity generation and decolorization of methyl orange in a
      two-chambered microbial fuel cell and bacterial diversity.
AB  - The objectives of this study were to investigate the simultaneous bioelectricity
      generation and decolorization of methyl orange (MO) in the anode chamber of
      microbial fuel cells (MFCs) in a wide concentration range (from 50 to 800 mg L(
      1)) and to reveal the microbial communities on the anode after the MFC was
      operated continuously for more than 6 months using MO-glucose mixtures as fuel.
      Interestingly, the added MO played an active role in the production of
      electricity. The maximum voltage outputs were 565, 658, 640, 629, 617, and 605 mV
      for the 1 g L(-1) glucose with 0, 50, 100, 200, 300, and 500 mg L(-1) of MO,
      respectively. The results of three groups of comparison experiments showed that
      accelerated decolorization of methyl orange (MO) was achieved in the MFC as
      compared to MFC in open circuit mode and MFC without extra carbon sources. The
      decolorization efficiency decreased with an increase of MO concentration in the
      studied concentration range for the dye load increased. A 454 high-throughput
      pyrosequencing revealed the microbial communities. Geobacter genus known to
      generate electricity was detected. Bacteroidia class, Desulfovibrio, and
      Trichococcus genus, which were most likely responsible for degrading methyl
      orange, were also detected.

PMID- 24910310
TI  - Effect of water composition on the photocatalytic removal of pesticides with
      different TiO2 catalysts.
AB  - The objective of this work is double-firstly to explore the photocatalytic
      efficiency of five different commercial TiO2 catalysts in the photodegradation of
      a mixture of pesticides classified by the EU as priority pollutants and secondly
      to analyze the correlation between their physicochemical properties and the
      inhibition of the studied photocatalytic process when natural water was employed.
      Photocatalytic efficiencies when ultrapure water was used seem to point out that
      surface area was not a prerequisite for the photodegradation of the selected
      mixture of pesticides. On the other hand, significant differences in total
      organic carbon (TOC) conversions were obtained with the two studied water
      compositions. On one side, Evonik materials appear to be mostly inhibited when
      natural water was employed, whereas on the other, it should be remarked that
      anatase Sigma-Aldrich (SA) and, particularly, Hombikat UV100 (HBK) materials
      presented a very limited photo-efficiency inhibition or even a higher initial
      rate of TOC removal when a natural water matrix was used, probably due to their
      specific surface properties (PZC, S BET). Therefore, heterogeneous photocatalysis
      has proved to be a promising technology for the degradation of the selected
      mixture of pesticides where the final photo-efficiency of the five commercial
      titania catalysts studied here responds to a complex balance between its surface
      and structural properties.

PMID- 24910311
TI  - FTIR gas-phase kinetic study on the reactions of some acrylate esters with OH
      radicals and Cl atoms.
AB  - Acrylate esters are alpha,beta-unsaturated esters that contain vinyl groups
      directly attached to the carbonyl carbon. These compounds are widely used in the
      production of plastics and resins. Atmospheric degradation processes of these
      compounds are currently not well understood. The kinetics of the gas phase
      reactions of OH radicals with methyl 3-methylacrylate and methyl 3,3
      dimethylacrylate were determined using the relative rate technique in a 50 L
      Pyrex photoreactor using in situ FTIR spectroscopy at room temperature (298 +/- 2
      K) and atmospheric pressure (708 +/- 8 Torr) with air as the bath gas. Rate
      coefficients obtained were (in units cm(3) molecule(-1) s(-1)): (3.27 +/- 0.33) *
      10(-11) and (4.43 +/- 0.42) * 10(-11), for CH3CH?CHC(O)OCH3 and
      (CH3)2CH?CHC(O)OCH3, respectively. The same technique was used to study the gas
      phase reactions of hexyl acrylate and ethyl hexyl acrylate with OH radicals and
      Cl atoms. In the experiments with Cl, N2 and air were used as the bath gases. The
      following rate coefficients were obtained (in cm(3) molecule(-1) s(-1)): k3
      (CH2?CHC(O)O(CH2)5CH3 + Cl) = (3.31 +/- 0.31) * 10(-10),
      k4(CH2?CHC(O)OCH2CH(CH2CH3)(CH2)3CH3 + Cl) = (3.46 +/- 0.31) * 10(-10),
      k5(CH2?CHC(O)O(CH2)5CH3 + OH) = (2.28 +/- 0.23) * 10(-11), and
      k6(CH2?CHC(O)OCH2CH(CH2CH3)(CH2)3CH3 + OH) = (2.74 +/- 0.26) * 10(-11). The
      reactivity increased with the number of methyl substituents on the double bond
      and with the chain length of the alkyl group in -C(O)OR. Estimations of the
      atmospheric lifetimes clearly indicate that the dominant atmospheric loss process
      for these compounds is their daytime reaction with the hydroxyl radical. In
      coastal areas and in some polluted environments, Cl atom-initiated degradation of
      these compounds can be significant, if not dominant. Maximum Incremental
      Reactivity (MIR) index and global warming potential (GWP) were also calculated,
      and it was concluded that these compounds have significant MIR values, but they
      do not influence global warming.

PMID- 24910312
TI  - Indication of airborne pollution by birch and spruce in the vicinity of copper
      smelter.
AB  - The aim of the study was determination of air pollution impact of the copper
      smelter in Bor and its surroundings (Serbia) by assessing the suitability of
      birch (Betula pendula Roth.) and spruce (Picea abies L.) for the purposes of
      biomonitoring and comparing it with previously published data from the same study
      area. The concentrations of Cu, Zn, Pb and Mn in leaves/needles, branches, roots
      and soil were determined. Sampling was performed during 2009 in two zones with
      high load of air pollution due to copper mining and smelting activities, and one
      background zone. Metal accumulation and translocation was evaluated in terms of
      biological factors. In addition, plant enrichment factor was calculated.
      According to the results, plant foliage was not enriched through soil, which
      indicates absorption from the air, with both species acting as excluders of Cu,
      Pb, Zn and Mn. Leaves were more enriched with all the metals than needles,
      indicating a better response of birch to airborne pollution than spruce. Cluster
      analysis showed different level of pollution at the sites, while correlations
      between Cu and Pb obtained by Principal Component Analysis indicated their
      anthropogenic origin. Regarding previously published results, beside birch
      leaves, pine needles (which showed higher level of response to pollution compared
      to linden leaves) could be applied in air biomonitoring surveys near copper
      smelters. 

PMID- 24910313
TI  - Public budgets for energy RD&D and the effects on energy intensity and pollution
      levels.
AB  - This study, based on the N-shaped cubic model of the environmental Kuznets curve,
      analyzes the evolution of per capita greenhouse gas emissions (GHGpc) using not
      just economic growth but also public budgets dedicated to energy-oriented
      research development and demonstration (RD&D) and energy intensity. The empirical
      evidence, obtained from an econometric model of fixed effects for 28 OECD
      countries during 1994-2010, suggests that energy innovations help reduce GHGpc
      levels and mitigate the negative impact of energy intensity on environmental
      quality. When countries develop active energy RD&D policies, they can reduce both
      the rates of energy intensity and the level of GHGpc emissions. This paper
      incorporates a moderating variable to the econometric model that emphasizes the
      effect that GDP has on energy intensity. It also adds a variable that reflects
      the difference between countries that have made a greater economic effort in
      energy RD&D, which in turn corrects the GHG emissions resulting from the energy
      intensity of each country. 

PMID- 24910315
TI  - Hydrogen-bonding in the pyrimidine...NH3 van der Waals complex: experiment and
      theory.
AB  - The pyrimidineNH3 van der Waals complex has been studied using a combination of
      resonant two-photon ionisation (R2PI) spectroscopy, ab initio molecular orbital
      calculations and multidimensional Franck-Condon analysis. The R2PI spectrum is
      assignable to a single stable conformer in which the ammonia molecule binds via
      two hydrogen bonds within the plane of the ring, in a location which minimises
      repulsion between the ammonia nitrogen lone pair and that of the second, more
      remote pyrimidine nitrogen in the 3 position on the opposite side of the ring.
      Ground state estimated CCSD(T) interaction energies were extrapolated to the
      complete basis set limit: these calculations found the dissociation energy of the
      most stable conformer, sigma(B), to be 20% larger than that of a second in-plane
      conformer, sigma(A), in which the ammonia forms a similar pseudo five-membered
      ring, bridging the nitrogen at the 1 position with the carbon at the 2 position.
      This conformation in turn was found to have a dissociation energy 35% larger than
      that of a pi-complex in which the ammonia binds above the plane of the aromatic
      ring. The results of multidimensional Franck-Condon simulations based on ab
      initio ground and excited state CASSCF and RICC2 geometry optimisations and
      vibrational frequency calculations showed good agreement with experiment. It is
      postulated that longer-range electrostatic interactions between the ammonia lone
      pair and the more distant of the two ring nitrogens on the pyrimidine, play a key
      role in determining which of the two in-plane structures is the more stable and
      which, therefore, is responsible for all of the spectral features observed in the
      R2PI spectrum.

PMID- 24910314
TI  - Contamination and distribution of parent, nitrated, and oxygenated polycyclic
      aromatic hydrocarbons in smoked meat.
AB  - Smoked meat is widely consumed in many areas, particularly in rural southwest
      China. High concentrations of polycyclic aromatic hydrocarbons (PAHs) in smoked
      meat could lead to adverse dietary exposure and health risks. In this study, 27
      parent PAHs (pPAHs), 12 nitrated PAHs (nPAHs), and 4 oxygenated PAHs (oPAHs) were
      measured in coal- and wood-smoked meats. The median concentrations of pPAHs,
      nPAHs, and oPAHs were as high as 1.66 * 10(3), 4.29, and 20.5 ng/g in the coal
      smoked meat and 2.54 * 10(3), 7.32, and 9.26 ng/g in the wood-smoked meat,
      respectively. Based on the relative potency factors of individual PAHs, the
      calculated toxic equivalent (TEQ) values of all pPAHs were 22.1 and 75.1 ng TEQ/g
      for the wood- and coal-smoked meats, respectively. The highest concentrations of
      PAHs can be found in the surface layer of skin and decrease exponentially with
      depth. Surface PAH concentrations correlated with concentrations of PAHs in
      household air and with the concentration in emission exhaust. Migration of PAHs
      from surface to interior portions of meat is faster in lean than in fat or skin,
      and oPAHs and pPAHs can penetrate deeper than pPAHs. The penetration ability of
      PAHs is negatively correlated with the molecular weight.

PMID- 24910317
TI  - Incarcerated gravid uterus: early manual reduction vs. late spontaneous
      resolution.

PMID- 24910318
TI  - Role of low- and high-frequency oscillations in the human hippocampus for
      encoding environmental novelty during a spatial navigation task.
AB  - The hippocampus plays a key role in the encoding and retrieval of information
      related to novel environments during spatial navigation. However, the neural
      basis for these processes in the human hippocampus remains unknown because it is
      difficult to directly measure neural signals in the human hippocampus. This study
      investigated hippocampal neural oscillations involved in encoding novel
      environments during spatial navigation in a virtual environment. Seven epileptic
      patients with implanted intracranial hippocampal depth electrodes performed three
      sessions of virtual environment navigation. Each session consisted of a
      navigation task and a location-recall task. The navigation task consisted of
      eight blocks, and in each block, the participant navigated to the location of
      four different objects and was instructed to remember the location of the
      objects. After the eight blocks were completed, a location-recall task was
      performed for each of the four objects. Intracranial electroencephalography data
      were monitored during the navigation tasks. Theta (5-8 Hz) and delta (1-4 Hz)
      oscillations were lower in the first block (novel environment) than in the eighth
      block (familiar environment) of the navigation task, and significantly increased
      from block one to block eight. By contrast, low-gamma (31-50 Hz) oscillations
      were higher in the first block than in the eighth block of the navigation task,
      and significantly decreased from block one to block eight. Comparison of sessions
      with high recall performance (low error between identified and actual object
      location) and low recall performance revealed that high-gamma (51-100 Hz)
      oscillations significantly decreased from block one to block eight only in
      sessions with high recall performance. These findings suggest that delta, theta,
      and low-gamma oscillations were associated with encoding of environmental novelty
      and high-gamma oscillations were important for the successful encoding of
      environmental novelty.

PMID- 24910319
TI  - Forearm soft tissue sarcoma: tumors characteristics and oncologic outcomes
      following limb salvage surgery.
AB  - BACKGROUND: Complex anatomy of the forearm may impact on local control and
      survivals of soft tissue sarcoma. Little is known about characteristics and
      oncologic outcomes following surgical treatment. METHODS: Demographic and tumor
      data of 117 patients with forearm soft tissue sarcoma were collected and
      analyzed. Following limb salvage, survivals, and prognostic factors were studied.
      RESULTS: Seventy-three patients were males (62%) and 53 (45%) were referred after
      unplanned excision. Pleomorphic undifferentiated sarcoma was most frequent (45%).
      The average tumor size was 5.1 cm and grade III histology was mostly identified
      (53%). With radiotherapy, local recurrence occurs in 8 patients (7%) and 30
      patients (24%) developed metastasis. Overall survival, disease free survival,
      local recurrence free survival, and metastasis free survival were 83%, 74%, 93%,
      and 74%, respectively. Better survival was found for grade I (80% vs. 60%) and
      small size (<5 cm) (72% vs. 47%). Large size tumor, extra-compartmental site,
      extramuscular, and virgin tumor were positive predictors of metastasis.
      CONCLUSION: Soft tissue sarcomas of the forearm are often referred after
      unplanned excision. Limb salvage was achieved for most and local recurrence
      remained low in context of radiotherapy. Metastatic progression remained
      frequent. Low grade and small size were predictors of survival.

PMID- 24910320
TI  - The comprehensive health care orientation process indicators explain hospital
      organisation's attractiveness: a Bayesian analysis of newly hired nurse and
      physician survey data.
AB  - AIM: To examine the relationship of a comprehensive health care orientation
      process with a hospital's attractiveness. BACKGROUND: Little is known about
      indicators of the employee orientation process that most likely explain a
      hospital organisation's attractiveness. METHOD: Empirical data collected from
      registered nurses (n = 145) and physicians (n = 37) working in two specialised
      hospital districts. A Naive Bayes Classification was applied to examine the
      comprehensive orientation process indicators that predict hospital's
      attractiveness. RESULTS: The model was composed of five orientation process
      indicators: the contribution of the orientation process to nurses' and
      physicians' intention to stay; the defined responsibilities of the orientation
      process; interaction between newcomer and colleagues; responsibilities that are
      adapted for tasks; and newcomers' baseline knowledge assessment that should be
      done before the orientation phase. CONCLUSIONS: The Naive Bayes Classification
      was used to explore employee orientation process and related indicators. The
      model constructed provides insight that can be used in designing and implementing
      the orientation process to promote the hospital organisation's attractiveness.
      IMPLICATIONS FOR NURSING MANAGEMENT: Managers should focus on developing fluently
      organised orientation practices based on the indicators that predict the
      hospital's attractiveness. For the purpose of personalised orientation,
      employees' baseline knowledge and competence level should be assessed before the
      orientation phase.

PMID- 24910321
TI  - A PET system design by using mixed detectors: resolution properties.
AB  - We investigate a cylindrical positron emission tomography (PET) system design
      strategy that employs two groups of detectors with different resolutions. The
      reason for considering this strategy is the observation that in many tasks one
      would want a higher resolution in a targeted region, which contains lesions or
      organs of interest, than that in the rest of the subject. Although one can design
      a PET system to meet the highest resolution required by the imaging task, this is
      not cost efficient because the superior resolution outside the target region is
      not needed. To address this issue, investigators have proposed the concept of an
      insert, in which a high-resolution detector (HRD) is inserted into a parent PET
      system to locally increase the image resolution. In this paper, we examine an
      alternative strategy in which the system is made of one arc of normal-resolution
      detectors with respect to, for example, whole-body imaging and one arc of HRDs.
      By using Monte Carlo simulations, we study the resolution properties of this
      system design and examine how they are affected by the location and size of the
      HRD arc. Our results show that the region obtained by connecting the edges of the
      HRD arc to the center of the field-of-view (FOV) can have significantly better
      resolution than that in the rest of the FOV, as well as better resolution
      uniformity. 

PMID- 24910322
TI  - Development of a procedure for the multiresidue analysis of pesticides in
      vineyard soils and its application to real samples.
AB  - A procedure for multiresidue analysis was developed for the extraction and
      determination of 17 pesticides, including herbicides, fungicides, and
      insecticides, as well as certain degradation products, in vineyard soils from La
      Rioja region (Spain). Different solvents and mixtures were tested in spiked
      pesticide-free soils, and pesticides were comparatively evaluated by gas
      chromatography with mass spectrometry and liquid chromatography with mass
      spectrometry. Recoveries >70%, with relative standard deviations <9%, were
      obtained when a mixture of methanol/acetone or a mixture of methanol/CaCl2 0.01 M
      for the most polar compounds was selected as the extraction solvent. Method
      validation was accomplished with acceptable linearity (r(2) >= 0.987) within the
      concentration range of 0.005-1 MUg/mL corresponding to 1.667-333.4 MUg/kg and
      0.835-167.1 MUg/kg for liquid chromatography with mass spectrometry and gas
      chromatography with mass spectrometry, respectively, and detection limits <0.4
      MUg/kg for the compounds were studied. The extraction method was applied to 17
      real vineyard soil samples, and terbuthylazine and its metabolite
      desethylterbuthylazine were the most ubiquitous compounds, as they were detected
      in the 100% of the soils analyzed. The presence of fungicides was also high, and
      the presence of insecticides was lower than other pesticides. The results confirm
      the usefulness of the optimized procedure for monitoring residues in vineyard
      soils. 

PMID- 24910323
TI  - Superior lithium storage in a 3D macroporous graphene framework/SnO2
      nanocomposite.
AB  - A three-dimensional (3D) interconnected graphene framework (GF)-based SnO2
      nanocomposite (3D SnO2/GFs) was prepared using self-assembly of polystyrene
      (PS)@SnO2 nanospheres and graphene oxide (GO) nanosheets under suitable pH
      conditions, followed by a thermal treatment. The electroactive material (SnO2) is
      anchored to the wall of electrochemically and ionically conductive 3D
      interconnected GFs. When used as anodes for LIBs, the 3D SnO2/GFs deliver an
      excellent reversible capacity (1244 mA h g(-1) in 50 cycles at 100 mA g(-1)) and
      outstanding rate capability (754 mA h g(-1) in 200 cycles at 1000 mA g(-1)). The
      ultra-small size of SnO2 (sub 10 nm) and dimensional confinement of SnO2
      nanoparticles by the wall of GFs limit the volume expansion upon lithium
      insertion, and the 3D interconnected porous structures serve as buffered spaces
      during charge-discharge and result in superior electrochemical performance by
      facilitating the electrolyte to contact the entire nanocomposite materials and
      reduce lithium diffusion length in the nanocomposite.

PMID- 24910324
TI  - Coalescent simulation in continuous space: algorithms for large neighbourhood
      size.
AB  - Many species have an essentially continuous distribution in space, in which there
      are no natural divisions between randomly mating subpopulations. Yet, the
      standard approach to modelling these populations is to impose an arbitrary grid
      of demes, adjusting deme sizes and migration rates in an attempt to capture the
      important features of the population. Such indirect methods are required because
      of the failure of the classical models of isolation by distance, which have been
      shown to have major technical flaws. A recently introduced model of extinction
      and recolonisation in two dimensions solves these technical problems, and
      provides a rigorous technical foundation for the study of populations evolving in
      a spatial continuum. The coalescent process for this model is simply stated, but
      direct simulation is very inefficient for large neighbourhood sizes. We present
      efficient and exact algorithms to simulate this coalescent process for arbitrary
      sample sizes and numbers of loci, and analyse these algorithms in detail.

PMID- 24910325
TI  - Direct synthesis of hexagonal NaGdF4 nanocrystals from a single-source precursor:
      upconverting NaGdF4 :Yb3+ ,Tm3+ and its composites with TiO2 for near-IR-driven
      photocatalysis.
AB  - A novel single-source precursor NaGd(TFA)4 (diglyme) (TFA=trifluoroacetate) was
      synthesized, characterized thoroughly, and used to obtain the hexagonal phase of
      NaGdF4 nanoparticles as an efficient matrix for lanthanide-doped upconverting
      nanocrystals (NCs) that convert near-infrared radiation into shorter-wavelength
      UV/visible light. These NCs were then used to prepare well-characterized
      TiO2@NaGdF4:Yb(3+),Tm(3+) nanocomposites to extend the absorption range of the
      TiO2 photocatalyst from the UV to the IR region. While the visible/near IR part
      of the photoluminescent spectra remains almost unaffected by the presence of
      TiO2, the UV part is strongly quenched due to the absorption of TiO2 above its
      gap at approximately 380 nm by energy transfer or FRET. Preliminary results on
      the photocatalytic activity of the above obtained nanocomposites are presented.

PMID- 24910326
TI  - An evaluation of resurgence of appropriate communication in individuals with
      autism who exhibit severe problem behavior.
AB  - We evaluated resurgence of mands exhibited by 3 individuals with autism and
      histories of problem behavior. The experimental conditions consisted of (a)
      reinforcement of a mand, (b) extinction, (c) reinforcement of a 2nd mand, and (d)
      extinction to test for resurgence of the 1st mand. This 4-component sequence was
      implemented 3 times with each participant, and resurgence occurred during 8 of 9
      tests for resurgence. Results are discussed in terms of implications for the
      prevention of clinical relapse. 

PMID- 24910327
TI  - [Perioperative medical treatment of old patients admitted with hip fracture].

PMID- 24910328
TI  - MRTF-A controls vessel growth and maturation by increasing the expression of CCN1
      and CCN2.
AB  - Gradual occlusion of coronary arteries may result in reversible loss of
      cardiomyocyte function (hibernating myocardium), which is amenable to therapeutic
      neovascularization. The role of myocardin-related transcription factors (MRTFs)
      co-activating serum response factor (SRF) in this process is largely unknown.
      Here we show that forced MRTF-A expression induces CCN1 and CCN2 to promote
      capillary proliferation and pericyte recruitment, respectively. We demonstrate
      that, upon G-actin binding, thymosin beta4 (Tbeta4), induces MRTF translocation
      to the nucleus, SRF-activation and CCN1/2 transcription. In a murine ischaemic
      hindlimb model, MRTF-A or Tbeta4 promotes neovascularization, whereas loss of
      MRTF-A/B or CCN1-function abrogates the Tbeta4 effect. We further show that, in
      ischaemic rabbit hindlimbs, MRTF-A as well as Tbeta4 induce functional
      neovascularization, and that this process is inhibited by angiopoietin-2, which
      antagonizes pericyte recruitment. Moreover, MRTF-A improves contractile function
      of chronic hibernating myocardium of pigs to a level comparable to that of
      transgenic pigs overexpressing Tbeta4 (Tbeta4tg). We conclude that MRTF-A
      promotes microvessel growth (via CCN1) and maturation (via CCN2), thereby
      enabling functional improvement of ischaemic muscle tissue. 

PMID- 24910329
TI  - Engineering uroporphyrinogen III methyltransferase as a red fluorescent reporter
      in E. coli.
AB  - Uroporphyrinogen III methyltransferase (UMT) is a novel reporter owing to the
      catalytic products in the cells that emit strong red fluorescence under UV light.
      Here, we engineered the gene encoding the functional barley UMT (bUMT) by error
      prone PCR and broadened the application UMT as a red fluorescent reporter in
      Escherichia coli. A variant, termed mbUMT, was selected and emitted stronger cell
      fluorescence than the wild type bUMT expressed in different E. coli strains,
      under different promoters and induction conditions respectively. The constructed
      mbUMT with a C-terminal ssrA tag was degraded in cells by the protease ClpXP
      encoded by E. coli chromosome, whereas the bUMT was expressed as active
      aggregates. Before they are exported to the periplasm, both proteins catalyze the
      substrate in the cytoplasm and emit cell fluorescence. The results suggested that
      the evolved bUMT is a better candidate to monitor in vivo degradation by E. coli
      ClpXP. 

PMID- 24910330
TI  - An alcohol oxidase of Phanerochaete chrysosporium with a distinct glycerol
      oxidase activity.
AB  - An intracellular alcohol oxidase (AOX) was isolated from the white-rot
      basidiomycete Phanerochaete chrysosporium (Pch), grown on l-lactate induction
      medium, and purified to electrophoretic homogeneity. The dimeric protein
      consisted of two identical 75kDa subunits. The open reading frame of 1,956bp
      resulted in a monomer consisting of 651 amino acids. The enzyme showed a pI at
      5.4, a pH optimum of 9, a temperature optimum at 50 degrees C, possessed putative
      conserved domains of the GMC superfamily, a FAD binding domain, and showed up to
      86% homology to alcohol oxidase sequences of Gloeophyllum trabeum and Coprinopsis
      cinerea. As was shown for the first time for an AOX from a basidiomycete, not
      only methanol, but also lower primary alcohols and glycerol were accepted as
      substrates. An assay based on aldehyde dehydrogenase confirmed d-glyceraldehyde
      as the product of the reaction. A bioprocess based on this enzyme could alleviate
      the problems associated with the huge side-stream of glycerol occurring during
      the manufacture of biodiesel, yielding the green oxidant hydrogen peroxide. 

PMID- 24910331
TI  - Bio-inspired morphological evolution of zinc oxide nanostructures on a tunable
      enzyme platform.
AB  - Diamine oxidase is a copper-containing enzyme with interesting structural
      dynamics sensitive to environmental conditions. The present work explores the
      applicability of the system as a tunable platform for the shape and size
      selective synthesis of zinc oxide nanoparticles under ambient conditions.
      Significant changes in the nanoscale morphology of ZnO have been observed, using
      scanning electron microscopy, with respect to changes in pH and gas atmosphere of
      the medium. More specifically, hexagonal plates of nanoscale ZnO were formed at
      pH below the isoelectric point of the enzyme and spherical particles at alkaline
      pH. Interestingly the average particle size of ZnO nanostructures increases with
      increasing oxygen content at acidic pH while the opposite trend is noticed at
      alkaline pH. The observations are explained on the basis of changes in the
      enzyme's surface charge, conformation and redox potential using a combination of
      techniques like zeta potential measurements, FTIR spectroscopy, fluorescence
      spectroscopy, open circuit potential studies and cyclic voltammetry. Thus the
      present work demonstrates the applicability of an enzyme as a dynamic bio
      template for the synthesis of a multitude of ZnO nanostructures which are
      expected to add newer insight into bottom-up fabrication of oxide nanostructures.

PMID- 24910332
TI  - Magnetic cross-linked enzyme aggregates (CLEAs): a novel concept towards carrier
      free immobilization of lignocellulolytic enzymes.
AB  - The enzymatic conversion of lignocellulosic biomass into biofuels has been
      identified as an excellent strategy to generate clean energy. However, the
      current process is cost-intensive as an effective immobilization approach to
      reuse the enzyme(s) has been a major challenge. The present study introduces the
      concept and application of novel magnetic cross-linked enzyme aggregates (mag
      CLEAs). Both mag-CLEAs and calcium-mag-CLEAs (Ca-mag-CLEAs) exhibited a 1.35 fold
      higher xylanase activity compared to the free enzyme and retained more than 80.0%
      and 90.0% activity, respectively, after 136h of incubation at 50 degrees C,
      compared to 50% activity retained by CLEAs. A 7.4 and 9.0 fold higher sugar
      release from lime-pretreated and NH4OH pre-treated sugar bagasse, respectively,
      was achieved with Ca-mag-CLEAs compared to the free enzymes. The present study
      promotes the successful application of mag-CLEAs and Ca-mag-CLEAs as carrier free
      immobilized enzymes for the effective hydrolysis of lignocellulolytic biomass and
      associated biofuel feedstocks. 

PMID- 24910333
TI  - Immobilized Candida antarctica lipase B on ZnO nanowires/macroporous silica
      composites for catalyzing chiral resolution of (R,S)-2-octanol.
AB  - ZnO nanowires were successfully introduced into a macroporous SiO2 by in situ
      hydrothermal growth in 3D pores. The obtained composites were characterized by
      SEM and XRD, and used as supports to immobilize Candida antarctica lipase B
      (CALB) through adsorption. The high specific surface area (233 m(2)/g) and strong
      electrostatic interaction resulted that the average loading amount of the
      composite supports (196.8 mg/g) was 3-4 times of that of macroporous SiO2 and
      approximate to that of a silica-based mesoporous material. Both adsorption
      capacity and the activity of the CALB immobilized on the composite supports
      almost kept unchanged as the samples were soaked in buffer solution for 48 h. The
      chiral resolution of 2-octanol was catalyzed by immobilized CALB. A maximum molar
      conversion of 49.1% was achieved with 99% enantiomeric excess of (R)-2-octanol
      acetate under the optimal condition: a reaction using 1.0 mol/L (R,S)-2-octanol,
      2.0 mol/L vinyl acetate and 4.0 wt.% water content at 60 degrees C for 8h. After
      fifteen recycles the immobilized lipase could retain 96.9% of relative activity
      and 93.8% of relative enantioselectivity.

PMID- 24910334
TI  - Directed evolution and mutagenesis of glutamate decarboxylase from Lactobacillus
      brevis Lb85 to broaden the range of its activity toward a near-neutral pH.
AB  - Glutamate decarboxylase (GAD) transforms l-glutamate into gamma-aminobutyric acid
      (GABA) with the consumption of a proton. GAD derived from lactic acid bacteria
      exhibits optimum activity at pH 4.0-5.0 and significantly loses activity at near
      neutral pH. To broaden the active range of the GAD GadB1 from Lactobacillus
      brevis Lb85 toward a near-neutral pH, irrational design using directed evolution
      and rational design using site-specific mutagenesis were performed. For directed
      evolution of GadB1, a sensitive high-throughput screening strategy based on a pH
      indicator was established. One improved mutant, GadB1(T17I/D294G/Q346H), was
      selected from 800 variants after one round of EP-PCR. It exhibited 3.9- and 25.0
      fold increase in activity and catalytic efficiency, respectively at pH 6.0.
      Through site-specific mutagenesis, several improved mutants were obtained, with
      GadB1(E312S) being the best one. The combined mutant
      GadB1(T17I/D294G/E312S/Q346H) showed even higher catalytic efficiency, 13.1- and
      43.2-fold that of wild-type GadB1 at pH 4.6 and 6.0, respectively. The amount of
      GABA produced in gadB1(T17I/D294G/Q346H)-, gadB1(E312S)- and
      gadB1(T17I/D294G/E312S/Q346H)-expressing Corynebacterium glutamicum ATCC 13032
      from endogenous l-glutamate increased by 9.6%, 20.3% and 63.9%, respectively.
      These results indicate that these mutations have beneficial effects on expanding
      the active pH range and on GABA biosynthesis, suggesting these GadB1 variants as
      potent candidates for GABA production. 

PMID- 24910335
TI  - Biosynthesis of 2-phenylethanol from glucose with genetically engineered
      Kluyveromyces marxianus.
AB  - 2-Phenylethanol (2-PE) is an aromatic alcohol with a rose scent, which is used in
      the cosmetics, fragrance and food industries. 2-PE is produced in a few yeast
      strains by Ehrlich pathway. In this study, Kluyveromyces marxianus was
      genetically engineered for overproduction of 2-PE from glucose. About 1.0g/L of 2
      PE was produced by overexpressing phenylpyruvate decarboxylase (ARO10) and
      alcohol dehydrogenase (ADH2) genes of Saccharomyces cerevisiae. A similar level
      of 2-PE was also produced from evolved K. marxianus, which was resistant to the
      phenylalanine analog, p-fluorophenylalanine. aroG(fbr) from Klebsiella pneumoniae
      encoding a feedback resistant mutant of 3-deoxy-D-arabino-heptulosonate-7
      phosphate (DHAP) synthase was overexpressed in the evolved K. marxianus. Finally,
      1.3g/L of 2-PE was produced from 20g/L glucose without addition of phenylalanine
      in the medium. 

PMID- 24910336
TI  - Inactivating effect of phenolic unit structures on the biodegradation of lignin
      by lignin peroxidase from Phanerochaete chrysosporium.
AB  - An imbalance of electron in an intramolecular electron transfer pathway was
      identified as the central factor causing inefficient degradation of lignin by the
      lignin peroxidase H8 from Phanerochaete chrysosporium (LiPH8). It was elucidated
      that dimeric lignins or monolignolic analogs containing free-hydroxyl phenolic
      groups were not only favorable substrates for the reduction of LiPH8 but also
      strong inhibitors depressing the enzymatic degradation of lignin. The data
      collectively demonstrated that disturbing the interaction between the free OH
      group on the phenolic structure and the surface active sites around Trp171 caused
      the primary deficiency in electron transport between Trp171 and the heme site,
      which severely inhibited the efficiency of lignin biodegradation by LiPH8/H2O2. 

PMID- 24910337
TI  - Stability of endoglucanases from mesophilic fungus and thermophilic bacterium in
      acidified polyols.
AB  - Recent developments in chemical pretreatments of lignocellulosic biomass using
      polyols as co-solvents (e.g., glycerol and ethylene glycol) at temperatures less
      than 100 degrees C may allow the effective use of thermostable and non
      thermostable cellulases in situ during the saccharification process. The
      potential of biomass saccharifying enzymes, endoglucanases (EG) from a
      thermophilic bacterium (Thermotoga maritima) and a mesophilic fungus (Trichoderma
      longibrachiatum), to retain their activity in aqueous buffer, acidified glycerol,
      and acidified ethylene glycol used as co-solvents at pretreatment temperatures at
      or below 100 degrees C were examined. The results show that despite its origin,
      T. longibrachiatum EG (Tl-EG) retained 75% of its activity after exposure to 100
      degrees C for 5 min in aqueous buffer while T. maritima EG (Tm-EG) retained only
      5% activity. However, at 90 degrees C both enzymes retained over 87% of their
      activity. In acidified (0.1% (w/w) H2SO4) glycerol, Tl-EG retained similar
      activity (80%) to that obtained in glycerol alone, while Tm-EG retained only 35%.
      With acidified ethylene glycol under these conditions, both Tl-EG and Tm-EG
      retained 36% of their activity. The results therefore show that Tl-EG is more
      stable in both acidified glycerol and ethylene glycol than Tm-EG. A preliminary
      kinetic study showed that pure glycerol improved the thermal stability of Tl-EG
      but destabilized Tm-EG, relative to the buffer solution. The half-lives of both
      Tl-EG and Tm-EG are 4.5 min in acidified glycerol, indicating that the
      effectiveness of these enzymes under typical pretreatment times of greater than
      15 min will be considerably diminished. Attempts have been made to explain the
      differences in the results obtained between the two enzymes.

PMID- 24910338
TI  - Proteomics analysis of Bacillus licheniformis in response to oligosaccharides
      elicitors.
AB  - The role of oligosaccharides as biotic elicitors has been recognised in the
      enhanced production of antibiotics from fungal and bacterial cultures. The yield
      of bacitracin A in cultures of Bacillus licheniformis was increased after
      supplementation with oligoguluronate (OG), and mannan oligosaccharides (MO) and
      its mechanism at transcription level been established already. However, the
      elicitation mechanism at post transcriptional level has not been reported so far.
      In this paper we investigate changes in proteomics of B. licheniformis in
      presence of the oligosaccharide elicitors OG and MO. Differentially expressed
      proteins were examined using 2D-PAGE stained with colloidal Coomassie and were
      further identified by LC-MS/MS. We identified 19 differentially expressed
      proteins including those involved in carbon metabolism, energy generation, amino
      acid biosynthesis, oxidative and general stress response. The novel findings of
      this work, together with previous reports, contribute to the unravelling of the
      overall mechanism of elicitation in B. licheniformis cultures and reliability of
      the use of these elicitors for potential industrial application. 

PMID- 24910339
TI  - Influence of setup and carbon source on the bacterial community of biocathodes in
      microbial electrolysis cells.
AB  - The microbial electrolysis cell (MEC) biocathode has shown great potential as
      alternative for expensive metals as catalyst for H2 synthesis. Here, the
      bacterial communities at the biocathode of five hydrogen producing MECs using
      molecular techniques were characterized. The setups differed in design (large
      versus small) including electrode material and flow path and in carbon source
      provided at the cathode (bicarbonate or acetate). A hydrogenase gene-based DNA
      microarray (Hydrogenase Chip) was used to analyze hydrogenase genes present in
      the three large setups. The small setups showed dominant groups of Firmicutes and
      two of the large setups showed dominant groups of Proteobacteria and
      Bacteroidetes. The third large setup received acetate but no sulfate (no sulfur
      source). In this setup an almost pure culture of a Promicromonospora sp.
      developed. Most of the hydrogenase genes detected were coding for bidirectional
      Hox-type hydrogenases, which have shown to be involved in cytoplasmatic H2
      production. 

PMID- 24910340
TI  - Selective prevention of cardiometabolic diseases in general practice: attitudes
      and working methods of male and female general practitioners before and after the
      introduction of the Prevention Consultation guideline in the Netherlands.
AB  - RATIONALE, AIMS AND OBJECTIVES: In 2011 the module cardiometabolic risk of the
      Prevention Consultation guideline was introduced in the Netherlands in order to
      prevent cardiometabolic diseases. We aimed to compare attitudes and working
      methods of Dutch general practitioners (GPs) towards selective prevention of
      cardiometabolic diseases before and after the introduction of the guideline and
      to study the effect of GP gender on these attitudes and working methods. METHODS:
      We compared attitudes and working methods in prevention of cardiometabolic
      diseases in a cross-sectional survey among Dutch GPs in 2013 to the results of a
      comparable study performed in 2008. RESULTS: Both in 2008 and 2013 30% responded.
      In 2013, more GPs reported to actively invite patients for preventive
      measurements. Thirty per cent of the GPs implemented the module cardiometabolic
      risk. In 2013, less GPs reported that it is worthwhile to make an effort to
      detect patients at increased risk for cardiometabolic diseases, and more GPs
      suggested that prevention may be performed by other stakeholders compared with
      2008. Financial support and evidence for prevention programmes were mentioned as
      main facilitators for prevention. In 2013, more male than female GPs actively
      invite patients for preventive measurements. CONCLUSIONS: More GPs report active
      preventive working methods after the introduction of the Prevention Consultation
      guideline, but only 30% implemented the guideline. More male than female GPs
      actively invite patients for preventive measurements. Compared with 2008 less GPs
      think it is worthwhile to make an effort to detect patients at increased risk and
      more GPs are willing to delegate preventive actions to other health institutions
      in 2013. As financial support and evidence for prevention are important
      facilitators for prevention, further research of the effectiveness of the
      guideline in preventing cardiometabolic diseases is necessary, and political
      choices have to be made in order to financially facilitate selective prevention
      in general practice.

PMID- 24910341
TI  - Pretreatment prediction of the outcome of response-guided peginterferon-alpha and
      ribavirin therapy for chronic hepatitis C.
AB  - BACKGROUND AND AIM: The accuracy for predicting virological outcomes of
      peginterferon-alpha and ribavirin therapy in patients with chronic hepatitis C is
      limited to approximately 80%, even with IL28B genotyping. Our in vitro study
      revealed that the numbers of (TA) dinucleotide repeats [(TA)n] of rs72258881,
      which is located in the promoter region of IL28B gene, might regulate IL28B
      transcription. We aimed to evaluate the usefulness of these host factors for
      predicting virological outcomes of this therapy in response-guided clinical
      settings. METHODS: A nationwide, multi-center prospective study in Japan
      determined IL28B (rs8099917) genotype, (TA)n of rs72258881, and amino acid
      substitutions of hepatitis C virus and used these for multivariate analysis
      together with other parameters at pretreatment. RESULTS: After enrolling 215
      patients with genotype 1 and high viral load from 23 hospitals between October
      2009 and February 2011, intent-to-treat analysis identified 202 patients in whom
      the final virological outcomes could be determined. Non-virological response by
      non-TT genotype was predicted with 79.7% accuracy. When combined with the (TA)n,
      the incidences of virological response tended to be higher in the longer (TA)n
      group, regardless of rs8099917 genotype. Multivariate logistic regression
      analysis revealed that rs8099917 non-TT genotype (P < 0.001), shorter (TA)n (P =
      0.011), mutation of amino acid 70 in the virus core region (P = 0.029), and lower
      levels of serum albumin (P = 0.036) were independently associated with non
      virological response. CONCLUSIONS: IL28B genotype and (TA)n of rs72258881 may
      independently affect virological outcomes of peginterferon-alpha and ribavirin as
      host factors, even in response-guided therapy.

PMID- 24910343
TI  - Effects of changes in muscle activation level and spine and hip posture on
      erector spinae fiber orientation.
AB  - INTRODUCTION: During lumbar flexion, the fiber orientation of the lumbar erector
      spinae (LES) muscle becomes oriented more along the spine compressive axis. It is
      unknown how changes in LES activation effect fiber orientation. METHODS:
      Ultrasound images of LES were collected during 2 sets of experimental conditions:
      (1) varying levels of LES activation while lying prone; and (2) varying spine and
      hip angles while seated. Electromyographic activity and lumbar spine and hip
      angles were also recorded. RESULTS: As LES activation increased, increases in
      fiber orientation (signifying increased orientation along the posterior shear
      axis) were found (P<0.001). Compared with the relaxed sitting posture, decreases
      in fiber orientation were found with full spine flexion and combined spine and
      hip flexion (P<0.001), but there were no changes with full hip flexion alone.
      CONCLUSIONS: Activation magnitude and spine posture both affect LES fiber
      orientation, thus modifying its ability to protect the spine against anterior
      shear forces.

PMID- 24910342
TI  - Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative
      leads to inhibition of advanced stages of breast cancer.
AB  - BACKGROUND AND PURPOSE: The psychoactive cannabinoid Delta(9) 
      tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD)
      can both reduce cancer progression, each through distinct anti-tumour pathways.
      Our goal was to discover a compound that could efficiently target both
      cannabinoid anti-tumour pathways. EXPERIMENTAL APPROACH: To measure breast cancer
      cell proliferation/viability and invasion, MTT and Boyden chamber assays were
      used. Modulation of reactive oxygen species (ROS) and apoptosis was measured
      using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in
      combination with cell flow cytometry. Changes in protein levels were evaluated
      using Western analysis. Orthotopic and i.v. mouse models of breast cancer
      metastasis were used to test the activity of cannabinoids in vivo. KEY RESULTS:
      CBD reduced breast cancer metastasis in advanced stages of the disease as the
      direct result of down-regulating the transcriptional regulator Id1. However, this
      was associated with moderate increases in survival. We therefore screened for
      analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC
      associated) and discovered the compound O-1663. This analogue inhibited Id1,
      produced a marked stimulation of ROS, up-regulated autophagy and induced
      apoptosis. Of all the compounds tested, it was the most potent at inhibiting
      breast cancer cell proliferation and invasion in culture and metastasis in vivo.
      CONCLUSIONS AND IMPLICATIONS: O-1663 prolonged survival in advanced stages of
      breast cancer metastasis. Developing compounds that can simultaneously target
      multiple cannabinoid anti-tumour pathways efficiently may provide a novel
      approach for the treatment of patients with metastatic breast cancer.

PMID- 24910344
TI  - Primary culture of human Schwann and schwannoma cells: improved and simplified
      protocol.
AB  - Primary culture of human Schwann cells (SCs) and vestibular schwannoma (VS) cells
      are invaluable tools to investigate SC physiology and VS pathobiology, and to
      devise effective pharmacotherapies against VS, which are sorely needed. However,
      existing culture protocols, in aiming to create robust, pure cultures, employ
      methods that can lead to loss of biological characteristics of the original
      cells, potentially resulting in misleading biological findings. We have developed
      a minimally manipulative method to culture primary human SC and VS cells, without
      the use of selective mitogens, toxins, or time-consuming and potentially
      transformative laboratory techniques. Schwann cell purity was quantified
      longitudinally using S100 staining in SC cultures derived from the great
      auricular nerve and VS cultures followed for 7 and 12 weeks, respectively. SC
      cultures retained approximately >=85% purity for 2 weeks. VS cultures retained
      approximately >=80% purity for the majority of the span of 12 weeks, with maximal
      purity of 87% at 2 weeks. The VS cultures showed high level of biological
      similarity (68% on average) to their respective parent tumors, as assessed using
      a protein array featuring 41 growth factors and receptors. Apoptosis rate in
      vitro negatively correlated with tumor volume. Our results, obtained using a
      faster, simplified culturing method than previously utilized, indicate that
      highly pure, primary human SC and VS cultures can be established with minimal
      manipulation, reaching maximal purity at 2 weeks of culture. The VS cultures
      recapitulate the parent tumors' biology to a great degree, making them relevant
      models to investigate VS pathobiology. 

PMID- 24910345
TI  - Innovative approaches to optimizing the delivery of vancomycin in individual
      patients.
AB  - The delivery of personalized antimicrobial therapy is a critical component in the
      treatment of patients with invasive infections. Vancomycin, the drug of choice
      for infections due to methicillin-resistant Staphylococcus aureus, requires the
      use of therapeutic drug monitoring (TDM) for delivery of optimal therapy. Current
      guidance on vancomycin TDM includes the measurement of a trough concentration as
      a surrogate for achieving an AUC to minimum inhibitory concentration (MIC) by
      broth microdilution (AUC/MICBMD) ratio>=400. Although trough-only monitoring has
      been widely integrated into clinical practice, there is a high degree of inter
      individual variability between a measured trough concentration and the actual AUC
      value. The therapeutic discordance between AUC and trough may lead to suboptimal
      outcomes among patients with infections due to less susceptible pathogens or
      unnecessarily increase the probability of acute kidney injury (AKI) in others.
      Given the potentially narrow vancomycin AUC range for optimal effect and minimal
      AKI, clinicians need a "real-time" system to predict accurately the AUC with
      limited pharmacokinetic (PK) sampling. This article reviews two innovative
      approaches for calculating the vancomycin AUC in clinical practice based on one
      or two drug concentrations. One such approach involves the use of Bayesian
      computer software programs to estimate the "true" vancomycin AUC value with
      minimal PK sampling and provide AUC-guided dosing recommendations at the bedside.
      An alternative involves use of two concentrations (peak and trough) and simple
      analytic equations to estimate AUC values. Both approaches provide considerable
      improvements over the current trough-only concentration monitoring method.

PMID- 24910346
TI  - The role of preoperative neutrophil-lymphocyte and platelet-lymphocyte ratio in
      patients after radical resection for gastric cancer.
AB  - The objective of this study was to investigate the impact of neutrophil
      lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) on the
      postoperative complication and long-term outcomes in patients with resectable
      gastric cancer (GC). A total of 377 patients who underwent curative resection for
      GC were enrolled. In logistic analysis, PLR (p = 0.09) was independently
      associated with the incidence of postoperative complication. The results of
      multivariate survival analysis showed the NLR and PLR were introduced as
      prognostic factors for operable GC, the NLR may represent a useful prognostic
      index for the prediction of overall survival (OS) in advanced GC (p = 0.021).

PMID- 24910348
TI  - Exploring the anti-apoptotic role of HAX-1 versus BCL-XL in cytokine-dependent
      bone marrow-derived cells from mice.
AB  - HS-1-associated protein X-1 (HAX-1) is a multi-functional protein that has been
      implicated in the regulation of apoptosis, cell motility and calcium homeostasis.
      In the present study, we set out to assess the postulated functional resemblance
      of HAX-1 to the BCL-2 family of anti-apoptotic proteins using non-transformed,
      cytokine-dependent murine bone marrow cells as a model system. BCL-X(L), but not
      HAX-1 protected against cytokine withdrawal-induced apoptosis while HAX-1 and BCL
      X(L) significantly reduced thapsigargin-triggered (calcium-dependent) apoptosis.
      The data argue in favor of cell type- and stimulus-specific roles of HAX-1 in
      regulation of cell survival.

PMID- 24910349
TI  - Dural ectasia in Marfan syndrome.

PMID- 24910347
TI  - Effect of general anesthesia in infancy on long-term recognition memory in humans
      and rats.
AB  - Anesthesia in infancy impairs performance in recognition memory tasks in
      mammalian animals, but it is unknown if this occurs in humans. Successful
      recognition can be based on stimulus familiarity or recollection of event
      details. Several brain structures involved in recollection are affected by
      anesthesia-induced neurodegeneration in animals. Therefore, we hypothesized that
      anesthesia in infancy impairs recollection later in life in humans and rats.
      Twenty eight children ages 6-11 who had undergone a procedure requiring general
      anesthesia before age 1 were compared with 28 age- and gender-matched children
      who had not undergone anesthesia. Recollection and familiarity were assessed in
      an object recognition memory test using receiver operator characteristic
      analysis. In addition, IQ and Child Behavior Checklist scores were assessed. In
      parallel, thirty three 7-day-old rats were randomized to receive anesthesia or
      sham anesthesia. Over 10 months, recollection and familiarity were assessed using
      an odor recognition test. We found that anesthetized children had significantly
      lower recollection scores and were impaired at recollecting associative
      information compared with controls. Familiarity, IQ, and Child Behavior Checklist
      scores were not different between groups. In rats, anesthetized subjects had
      significantly lower recollection scores than controls while familiarity was
      unaffected. Rats that had undergone tissue injury during anesthesia had similar
      recollection indices as rats that had been anesthetized without tissue injury.
      These findings suggest that general anesthesia in infancy impairs recollection
      later in life in humans and rats. In rats, this effect is independent of
      underlying disease or tissue injury. 

PMID- 24910350
TI  - Anesthetic management in pregnant patients with severe idiopathic pulmonary
      arterial hypertension.

PMID- 24910351
TI  - Pregnant women's views on informed consent for research in labour.
AB  - BACKGROUND: Studies of the optimal treatment of accidental dural puncture
      occurring during epidural insertion in labour are difficult for practical reasons
      and because of the ethical issues around seeking consent. In a recent study of
      accidental dural puncture, participants were assigned to one of two treatment
      groups and only informed about the study and consent sought, after treatment. We
      sought the views of parturients on the timing of consent for such a study.
      METHODS: After ethical approval and written consent, 100 nulliparous women in the
      third trimester of pregnancy completed a structured, facilitated questionnaire,
      rating the acceptability of the consent process occurring: (i) in antenatal
      clinic; (ii) after the epidural was requested in labour; (iii) after the
      accidental dural puncture had occurred but before treatment; (iv) after the
      allocated treatment; or (v) without consent (waived consent). Results were
      analysed with the Friedman and Wilcoxon signed-rank tests. RESULTS: Antenatal
      consent was considered the most acceptable option, whilst consent on request for
      epidural analgesia and after accidental dural puncture were least acceptable.
      Consent after treatment and waived consent were rated in-between these extremes.
      There was a statistically significant difference between these three groups
      (P<0.0001). There was a wide range of opinions on each option presented.
      CONCLUSIONS: Antenatal consent was the preferred option but if this is not
      possible and the need for the research is strong, consent for the use of women's
      data after intervention, or waived consent, is acceptable to many women. It is
      important to seek the views of the participants themselves before planning
      research with difficult ethical aspects.

PMID- 24910352
TI  - Termination of paroxysmal supraventricular tachycardia with remifentanil in a
      parturient with tachycardia-induced cardiomyopathy.

PMID- 24910353
TI  - Anticoagulant prescribing practices and anesthetic interventions among
      anticoagulated pregnant patients: a retrospective study.
AB  - BACKGROUND: The peripartum management of anticoagulated patients poses important
      challenges for obstetric anesthesiologists, especially when deciding to perform
      neuraxial block. However, there is limited evidence evaluating anticoagulant
      prescribing practices and neuraxial block utilization in this setting. Our
      objective was to examine peripartum anticoagulant prescribing and anesthetic
      practices in a cohort of anticoagulated patients receiving subcutaneous
      enoxaparin, and subcutaneous or intravenous unfractionated heparin. METHODS: We
      performed a retrospective study of anticoagulant prescribing patterns and
      anesthetic interventions among patients receiving enoxaparin and/or
      unfractionated heparin who delivered at a USA obstetric center over a seven-year
      period. RESULTS: We identified 101 patients who received enoxaparin and/or
      unfractionated heparin before delivery. Thirty-nine (38.6%) patients received
      enoxaparin only, 41 (40.6%) patients received enoxaparin bridged to subcutaneous
      unfractionated heparin, 11 (10.9%) patients received enoxaparin and were
      converted to intravenous unfractionated heparin and 10 (9.9%) patients received
      only subcutaneous unfractionated heparin. The overall rate of neuraxial block
      utilization was 80.2%. The median [IQR] time-period between the last dose of
      enoxaparin and neuraxial block was significantly shorter for patients who
      received only enoxaparin vs. enoxaparin with subcutaneous unfractionated heparin
      (54h [12-192h] (n=26) vs. 216h [39-504h] (n=23), P=0.04). Among patients who
      received only subcutaneous unfractionated heparin, the time period between
      unfractionated heparin and neuraxial block was 24h [19-51h]. CONCLUSION: In this
      study, the neuraxial block rate was high among patients receiving enoxaparin
      and/or subcutaneous unfractionated heparin with patients undergoing relatively
      long periods off anticoagulation. Careful multidisciplinary planning is
      recommended for the peripartum management of anticoagulated pregnant patients.

PMID- 24910354
TI  - Awake oral fibre-optic intubation in patients with Klippel-Feil syndrome.

PMID- 24910355
TI  - Rules of boron-nitrogen doping in defect graphene sheets: a first-principles
      investigation of band-gap tuning and oxygen reduction reaction catalysis
      capabilities.
AB  - Introduction of defects and nitrogen doping are two of the most pursued methods
      to tailor the properties of graphene for better suitability to applications such
      as catalysis and energy conversion. Doping nitrogen atoms at defect sites of
      graphene and codoping them along with boron atoms can further increase the
      efficiency of such systems due to better stability of nitrogen at defect sites
      and stabilization provided by B-N bonding. Systematic exploration of the possible
      doping/codoping configurations reflecting defect regions of graphene presents a
      prevalent doping site for nitrogen-rich BN clusters and they are also highly
      suitable for modulating (0.2-0.9 eV) the band gap of defect graphene. Such
      codoped systems perform significantly better than the platinum surface, undoped
      defect graphene, and the single nitrogen or boron atom doped defect graphene
      system for dioxygen adsorption. Significant stretching of the O-O bond indicates
      a lowering of the bond breakage barrier, which is advantageous for applications
      in the oxygen reduction reaction.

PMID- 24910356
TI  - Relationship between atherosclerotic risk factors and aortic plaques in patients
      with first-ever ischaemic stroke.
AB  - OBJECTIVE: Aortic plaque is considered a risk factor of ischaemic stroke, and
      both ulceration and plaque thickness are considered important. However, the
      relative importance of aortic plaque and carotid plaque remains unclear. The
      purpose of this study is to clarify the relation between aortic and carotid
      plaque lesions and atherosclerotic risk factors in patients with acute ischaemic
      stroke. METHODS: We enrolled 76 patients with first-ever ischaemic stroke,
      undergoing transoesophageal echocardiography, whose aetiology of ischaemic stroke
      was unknown. We divided the patients into two groups according to aortic plaque
      thickness, based on previous reports, i.e., a high-risk group (over 4mm) and a
      low-risk group (less than 4mm). We also examined several atherosclerotic risk
      factors. RESULTS: Mean age, gender and hypertension was not significantly
      different between the low-risk and high-risk group. HDL-cholesterol (P<0.01),
      LDL/HDL ratio (P<0.05), non-HDL-cholesterol (P<0.05), HbA1c (P<0.05) and eGFR
      (P<0.01) were significantly different between the two groups. Max plaque
      thickness in the carotid artery was correlated with aortic plaque lesions.
      CONCLUSION: Multiple atherosclerotic risk factors are associated with greater
      aortic plaque lesions. Aortic plaque is important not only as an embolic source,
      but also as one of the atherosclerotic markers.

PMID- 24910357
TI  - A Spanish version of the Skin Cancer Index: a questionnaire for measuring quality
      of life in patients with cervicofacial nonmelanoma skin cancer.
AB  - INTRODUCTION: The Skin Cancer Index (SCI) is the first specific patient-reported
      outcome measure for patients with cervicofacial nonmelanoma skin cancer. To date,
      only the original English version has been published. OBJECTIVES: To develop a
      Spanish version of the SCI that is semantically and linguistically equivalent to
      the original, and to evaluate its measurement properties in this different
      cultural environment. MATERIAL AND METHODS: A cross-sectional study was conducted
      of the cultural adaptation and empirical validation of the questionnaire,
      analysing the psychometric properties of the new index at different stages.
      RESULTS: Of 440 patients recruited to the study, 431 (95%) completed the Spanish
      version of the SCI questionnaire, in a mean time of 6.3 min (SD 2.9). Factor
      analysis of the scale revealed commonality and loading values of < 0.5 for three
      of the 15 items. The remaining 12 items converged into two components:
      appearance/social aspects (seven items) and emotional aspects (five items). Both
      domains presented a high level of internal consistency, with Cronbach's alpha
      values above 0.8. The convergent-discriminant validity analysis produced
      correlations higher than 0.3 for the mental component of the Short Form Health
      Survey-12v2 Health Questionnaire (correlation coefficient 0.39) and the
      Dermatology Quality of Life Index (correlation coefficient -0.30). In the test
      retest, nine of the 12 items produced a weighted kappa value exceeding 0.4, and
      for the remaining three items, the absolute agreement percentage exceeded 60%.
      CONCLUSIONS: The Spanish version of the SCI quality of life scale has been
      satisfactorily adapted and validated for use in Spanish-speaking countries and
      populations.

PMID- 24910359
TI  - Microscopic bio-corrosion evaluations of magnesium surfaces in static and dynamic
      conditions.
AB  - Biodegradable materials including biodegradable metals are continuously being
      investigated for the development of next generation cardiovascular stents.
      Predictive in vitro tests are needed that could evaluate potential materials
      while simulating in vivo conditions. In this manuscript we report the microscopic
      bio-corrosion evaluations of magnesium surfaces in static and dynamic conditions.
      A corrosion test bench was designed and fabricated and static and dynamic
      corrosion tests were carried out with samples of magnesium alloy. The fluid wall
      shear stress equation and the Churchill's friction factor equation were used to
      calculate the fluid velocity required to generate the desired shear stress on
      samples in the test bench. Static and dynamic corrosion tests at 24 and 72 h were
      carried out at 0.88 Pa shear stress mimicking the in vivo shear stress.
      Microscopic evaluations of the corroded surfaces were carried out by optical,
      scanning electron microscopy and energy dispersive X-ray spectroscopy to evaluate
      the corrosion behaviour and surface properties of the test samples. The surface
      and interface analysis of magnesium samples post test indicated that dynamic
      conditions prevented the build-up of corrosion by-products on the sample surface
      and the corrosion mechanism was uniform as compared to static conditions. The use
      of a masking element to restrict the exposed area of the sample didn't result in
      increased corrosion at the boundary. Thus, we have demonstrated the feasibility
      of the designed test bench as a viable method for bio-corrosion surface analysis
      under dynamic corrosion conditions for potential biodegradable cardiovascular
      stent materials. 

PMID- 24910358
TI  - Guanine- 5-carboxylcytosine base pairs mimic mismatches during DNA replication.
AB  - The genetic information encoded in genomes must be faithfully replicated and
      transmitted to daughter cells. The recent discovery of consecutive DNA
      conversions by TET family proteins of 5-methylcytosine into 5
      hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) suggests
      these modified cytosines act as DNA lesions, which could threaten genome
      integrity. Here, we have shown that although 5caC pairs with guanine during DNA
      replication in vitro, G.5caC pairs stimulated DNA polymerase exonuclease activity
      and were recognized by the mismatch repair (MMR) proteins. Knockdown of thymine
      DNA glycosylase increased 5caC in genome, affected cell proliferation via MMR,
      indicating MMR is a novel reader for 5caC. These results suggest the epigenetic
      modification products of 5caC behave as DNA lesions. 

PMID- 24910360
TI  - Mitigated Tregs and augmented Th17 cells and cytokines are associated with
      severity of experimental autoimmune neuritis.
AB  - Experimental autoimmune neuritis (EAN), an animal model of human Guillain-Barre
      syndrome, has long been considered as a T helper (Th) 1 cell-mediated autoimmune
      disorder. However, deficiency of IFN-gamma, a signature Th1 cytokine, aggravated
      EAN, with features of elevated production of IL-17A, despite an alleviated
      systemic Th1 immune response. We hypothesized that Th17 cells and their cytokines
      might play a pathogenic role in EAN. To further clarify the roles of these Th and
      regulatory T cell (Treg) cytokines in the pathogenesis of EAN and their
      interrelationship, we investigated the expression of Th1/Th2/Th17/Treg cytokines
      in EAN in this study. We found that the levels of Th17 cells and IL-17A in cauda
      equina (CE)-infiltrating cells and splenic mononuclear cells (MNCs) as well as in
      serum paralleled the disease evolution, which increased progressively during the
      initiation stage and reached higher value at the peak of EAN. The same pattern
      was also noticed for the expression of IL-22. The diverse expression profiles of
      FoxP3, IL-17 receptors A and C were seen in CE-infiltrating cells and splenic
      MNCs in EAN. These findings indicate a major pro-inflammatory role of Th17 cells
      and IL-17A in the pathogenesis of EAN. Therapeutic interventions may be focused
      upon inhibiting Th17 cells and their cytokines in the early phase of EAN, so as
      to delay and suppress clinical signs of the disease, which has relevance for
      future studies on pathogenesis and treatment of GBS in humans. 

PMID- 24910361
TI  - Predicting outcome following psychological therapy in IAPT (PROMPT): a
      naturalistic project protocol.
AB  - BACKGROUND: Depression and anxiety are highly prevalent and represent a
      significant and well described public health burden. Whilst first line
      psychological treatments are effective for nearly half of attenders, there remain
      a substantial number of patients who do not benefit. The main objective of the
      present project is to establish an infrastructure platform for the identification
      of factors that predict lack of response to psychological treatment for
      depression and anxiety, in order to better target treatments as well as to
      support translational and experimental medicine research in mood and anxiety
      disorders. METHODS/DESIGN: Predicting outcome following psychological therapy in
      IAPT (PROMPT) is a naturalistic observational project that began patient
      recruitment in January 2014. The project is currently taking place in Southwark
      Psychological Therapies Service, an Improving Access to Psychological Therapies
      (IAPT) service currently provided by the South London and Maudsley NHS Foundation
      Trust (SLaM). However, the aim is to roll-out the project across other IAPT
      services. Participants are approached before beginning treatment and offered a
      baseline interview whilst they are waiting for therapy to begin. This allows us
      to test for relationships between predictor variables and patient outcome
      measures. At the baseline interview, participants complete a diagnostic
      interview; are asked to give blood and hair samples for relevant biomarkers, and
      complete psychological and social questionnaire measures. Participants then
      complete their psychological therapy as offered by Southwark Psychological
      Therapies Service. Response to psychological therapy will be measured using
      standard IAPT outcome data, which are routinely collected at each appointment.
      DISCUSSION: This project addresses a need to understand treatment response rates
      in primary care psychological therapy services for those with depression and/or
      anxiety. Measurement of a range of predictor variables allows for the detection
      of bio-psycho-social factors which may be relevant for treatment outcome. This
      will enable future clinical decision making to be based on the individual needs
      of the patient in an evidence-based manner. Moreover, the identification of
      individuals who fail to improve following therapy delivered by IAPT services
      could be utilised for the development of novel interventions.

PMID- 24910362
TI  - Dysplasia and cancer screening in 21st century.
AB  - Cancer is the second leading cause of death in the United States, and is
      projected to overtake cardiovascular diseases as the number one cause of
      mortality in adults within a decade. Cancer screening offers an opportunity to
      detect cancer precursor lesions at early stages, and hence preemptively manage
      and prevent development of frank cancers. Despite tremendous technological
      advances over last decade, which allow us to study genomic/epigenomic and
      proteomic profile of cells with unprecedented details, it has been difficult to
      develop non-invasive biomarkers with high sensitivity and specificity that can
      have clinical applications. Dysplasia, which requires histopathological
      examination of the tissue, remains the best marker of propensity to develop
      cancer, and hence the best available surrogate biomarker. However, procuring
      tissues for detection of dysplasia is highly invasive and economically unviable
      for most visceral malignancies. Therefore, there is emphasis on developing
      circulating biomarkers through a consortium approach where high-performing
      biomarkers in basic research are tested in large collaborative clinical settings
      to assess their clinical efficacy. In this review, we have discussed fundamental
      principles of cancer screening, difficulties in developing novel and effective
      biomarkers, continuing reliance on dysplasia as best available surrogate marker
      for cancer screening, as well as briefly highlighted newer screening modalities. 

PMID- 24910363
TI  - A "twist" on S1S2: descending colon volvulus causing severe left hemi-diaphragm
      elevation.

PMID- 24910364
TI  - Head and neck myiasis, cutaneous malignancy, and infection: a case series and
      review of the literature.
AB  - BACKGROUND: There is a paucity of literature on wound myiasis of the head and
      neck originating in the United States. To our knowledge, only three reports
      during the past 20 years exist in the literature. Even less common is a case of
      recurrent myiasis, with only one report published from India during the 1970s.
      There is often a preconceived notion that larvae are noninvasive and "only eat
      dead tissue." This mentality must be corrected; invasive larvae exist, there are
      unique myiasis-related infections, and serious complications can occur. We review
      the literature and describe recent cases of head and neck myiasis treated at our
      institution in upstate New York. CASE REPORTS: Four cases, all initially
      presenting to the emergency department, were identified. Each case was
      superimposed on cutaneous malignancy and all patients presented with leukocytosis
      and positive blood or wound cultures. In the case of the recurrent myiasis,
      initial treatment was external beam radiation therapy for the malignancy, which
      had the added benefit of eradicating the larvae. Treatment for the other cases
      was limited to antibiotics and supportive care for medical comorbidities. WHY
      SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Serious complications can
      develop from head and neck myiasis and, in our experience, an underlying
      malignancy should be suspected. Proper management is critical and should include,
      at a minimum, empiric antibiotics, tetanus prophylaxis, biopsy of the surrounding
      tissue, and reporting to the appropriate health agency. Additional management can
      include bedside debridement, pharmacologic antiparasitics, and treatment of the
      underlying disorder.

PMID- 24910365
TI  - Using social bonding theory to examine 'recovery' in a forensic mental health
      hospital: A qualitative study.
AB  - BACKGROUND: For people living with mental illness, recovery involves learning to
      overcome and manage their symptoms and striving to live fulfilling lives. The
      literature on achieving recovery emphasises the importance of social connections
      and positive role models. Hirschi's social bonding theory posits that an
      individual's attachment to others, belief in social norms, and their commitment
      and involvement in conventional activities are the major contributors to
      normalising social behaviour. AIMS: The aim of this study is to understand the
      qualities of service identified by patients in a forensic hospital as being
      important and meaningful to recovery. METHODS: Semi-structured interviews with 30
      inpatients in a forensic mental health hospital in British Columbia, Canada, were
      audio recorded, and the transcriptions were analysed using thematic analysis.
      RESULTS: Five themes emerged: involvement in programmes, belief in rules and
      social norms, attachment to supportive individuals, commitment to work-related
      activities and concern about indeterminacy of stay. CONCLUSIONS: The first four
      themes map closely onto Hirschi's criminologically derived social bonding theory;
      however, indeterminacy of stay also arose as a common theme. In addition, the
      theory was too simple in its separation of elements; our data suggested the
      complex integration of themes. Our findings may be useful for informing
      evaluation of forensic mental health services.

PMID- 24910366
TI  - MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in
      Chronic Chagas disease Cardiomyopathy.
AB  - BACKGROUND/METHODS: Chagas disease is caused by an intracellular parasite,
      Trypanosoma cruzi, and it is a leading cause of heart failure in Latin America.
      The main clinical consequence of the infection is the development of a Chronic
      Chagas disease Cardiomyopathy (CCC), which is characterized by myocarditis,
      hypertrophy and fibrosis and affects about 30% of infected patients. CCC has a
      worse prognosis than other cardiomyopathies, like idiopathic dilated
      cardiomyopathy (DCM). It is well established that myocardial gene expression
      patterns are altered in CCC, but the molecular mechanisms underlying these
      differences are not clear. MicroRNAs are recently discovered regulators of gene
      expression, and are recognized as important factors in heart development and
      cardiovascular disorders (CD). We analyzed the expression of nine different
      miRNAs in myocardial tissue samples of CCC patients in comparison to DCM patients
      and samples from heart transplant donors. Using the results of a cDNA microarray
      database on CCC and DCM myocardium, signaling networks were built and nodal
      molecules were identified. RESULTS: We observed that five miRNAs were
      significantly altered in CCC and three in DCM; importantly, three miRNAs were
      significantly reduced in CCC as compared to DCM. We observed that multiple gene
      targets of the differentially expressed miRNAs showed a concordant inverse
      expression in CCC. Significantly, most gene targets and involved networks belong
      to crucial disease-related signaling pathways. CONCLUSION: These results suggest
      that miRNAs may play a major role in the regulation of gene expression in CCC
      pathogenesis, with potential implication as diagnostic and prognostic tools.

PMID- 24910367
TI  - Narrow-Diameter versus Standard-Diameter Implants and Their Effect on the Need
      for Guided Bone Regeneration: A Virtual Three-Dimensional Study.
AB  - PURPOSE: Narrow-diameter implants (NDIs) are proven treatment options for
      completely edentulous patients with severely resorbed alveolar ridges. The aim of
      this study was to evaluate virtually whether or not the implant diameter affects
      the need for ridge augmentation in edentulous patients, using a 3D planning
      software program. MATERIALS AND METHODS: Existing cone beam CT scans of 200
      outpatients (100 maxillae, 100 mandibles) were selected, and treatment was
      planned in a virtual 3D planning software program with either 3.3 mm-diameter
      implants (test group) or 4.1 mm-diameter implants (control group). Statistical
      analysis was performed. RESULTS: A total of 1,760 implants were virtually planned
      (880 implants each for test and control groups). Overall, significantly
      associated with the absence or need for ridge augmentation as compared with need
      for ridge augmentation (p < .0001). Use of the 3.3 mm-diameter implants increased
      the odds ratio for ridge augmentation being unnecessary by 2.2 (95% confidence
      interval) relative to the 4.1 mm-diameter implants. CONCLUSIONS: Use of NDIs was
      able to provide a statistically significant reduction in need for bone grafting
      among completely edentulous patients. More clinical longitudinal studies are
      necessary to confirm the long-term success of their use.

PMID- 24910368
TI  - Testing for levamisole and cocaine in hair samples for the diagnosis of
      levamisole-related panniculitis.

PMID- 24910369
TI  - Absolute monocyte count predicts overall survival in mantle cell lymphomas:
      correlation with tumour-associated macrophages.
AB  - Mantle cell lymphoma (MCL) is characterized by a variable clinical course in
      which patients can experience indolent disease or frequent relapses despite a
      good initial response to conventional therapy. Risk stratification of MCL is most
      frequently performed using the MCL International Prognostic Index (MIPI). Recent
      studies indicate that the peripheral blood absolute monocyte count (AMC) and
      tumour-associated macrophages may reflect the state of the tumour
      microenvironment in lymphomas. The significance of AMC and tumour-associated
      macrophages in the clinical course of MCL is unknown. The prognostic impact of
      the AMC, of CD68 expression and of CD163 expression was retrospectively examined
      in 103 MCL samples using the receiver operating characteristic curved. Patients
      with an AMC >= 375 cells/MUL at diagnosis were more likely to present with
      advanced-stage disease (p = 0.026), leukocytosis (p < 0.001), lymphocytosis (p =
      0.01) and granulocytosis (p = 0.003). On univariate analysis, a high AMC (>=375
      cells/MUL) correlated with poorer overall survival (OS) (p = 0.01). Neither CD68
      nor CD163 expression was significantly associated with either OS or event-free
      survival. Multivariate analysis showed that a high AMC was a prognostic factor
      for OS, independent of the MIPI [hazards ratio (HR), 1.811; 95% confidence
      interval, 1.018-3.223; p = 0.043]. This study demonstrates that the AMC at the
      time of diagnosis is an independent prognostic factor for OS in MCL, which
      suggests the possibility that AMC may be used in addition to the MIPI to predict
      outcome in patients with MCL.

PMID- 24910371
TI  - [Is magnetic resonance imaging really necessary for evaluating poor patellar
      alignment? The Peruvian experience].

PMID- 24910370
TI  - Initiation of sporulation in Clostridium difficile: a twist on the classic model.
AB  - The formation of dormant endospores is a complex morphological process that
      permits long-term survival in inhospitable environments for many Gram-positive
      bacteria. Sporulation for the anaerobic gastrointestinal pathogen Clostridium
      difficile is necessary for survival outside of the gastrointestinal tract of its
      host. While the developmental stages of spore formation are largely conserved
      among endospore-forming bacteria, the genus Clostridium appears to be missing a
      number of conserved regulators required for efficient sporulation in other spore
      forming bacteria. Several recent studies have discovered novel mechanisms and
      distinct regulatory pathways that control the initiation of sporulation and early
      sporulation-specific gene expression. These differences in regulating the
      decision to undergo sporulation reflects the unique ecological niche and
      environmental conditions that C. difficile inhabits and encounters within the
      mammalian host. 

PMID- 24910372
TI  - Genetic differentiation of brackish water populations of cod Gadus morhua in the
      southern Baltic, inferred from genotyping using SNP-arrays.
AB  - The Baltic is a semi-enclosed sea characterised by decreasing salinity in the
      eastern and northern direction with only the deeper parts of the southern Baltic
      suitable as spawning grounds for marine species like cod. Baltic cod exhibits
      various adaptations to brackish water conditions, yet the inflow of salty North
      Sea water near the bottom remains an influence on the spawning success of the
      Baltic cod. The eastern Baltic population has been very weakly studied in
      comparison with the western population. The aim of this study is to demonstrate
      for the first time genetic differentiation by the use of a large number of SNPs
      between eastern and western Baltic populations existing in differentiated
      salinity conditions. Two cod samples were collected from the Bay of Gdansk,
      Poland and one from the Kiel Bight, Germany. Samples were genotyped using a cod
      derived SNP-array (Illumina) with 10 913 SNPs. A selection of diagnostic SNPs was
      performed. A set of 7944 validated SNPs were analysed to assess the
      differentiation of three samples of cod. Results indicated a clear distinctness
      of the Kiel Bight from the populations of the eastern Baltic. FST comparison
      between both eastern samples was non-significant. Clustering analysis, principal
      coordinates analysis and assignment test clearly indicated that the eastern
      samples should be considered as one subpopulation, well differentiated from the
      western subpopulation. With the SNP approach, no differentiation between groups
      containing 'healthy' and 'non-healthy' cod individuals was observed. 

PMID- 24910373
TI  - Dissemination in Japan of multidrug-resistant Pseudomonas aeruginosa isolates
      producing IMP-type metallo-beta-lactamases and AAC(6')-Iae/AAC(6')-Ib.
AB  - The spread throughout Japan of antibiotic-resistance factors in multidrug
      resistant (MDR) Pseudomonas aeruginosa isolates was investigated
      epidemiologically, using immunochromatographic assays specific for IMP-type
      metallo-beta-lactamases (IMPs) and aminoglycoside 6'-N-acetyltransferase
      [AAC(6')]-Iae and -Ib. Three hundred MDR P. aeruginosa isolates were obtained
      during each of two years, 2011 and 2012, from 190 hospitals in 39 prefectures in
      Japan. The percentage of P. aeruginosa isolates producing IMPs, AAC(6')-Iae or
      AAC(6')-Ib increased significantly from 170/300 (56.7%) in 2011 to 230/300
      (76.7%) in 2012, with 134/170 (78.8%) in 2011 and 179/230 (77.8%) in 2012
      producing both IMP and either AAC(6')-Iae or AAC(6')-Ib. The MICs of antibiotics,
      including cephalosporins and carbapenems, were markedly higher for isolates that
      did than did not produce these resistance factors. These results indicated that
      MDR P. aeruginosa producing IMPs, AAC(6')-Iae or AAC(6')-Ib have spread
      throughout Japan and that these antibiotic-resistance factors are useful markers
      for monitoring MDR P. aeruginosa in Japan.

PMID- 24910374
TI  - Brucella melitensis sternal osteomyelitis following median sternotomy.
AB  - Human brucellosis, a zoonotic infection, may present with a range of symptoms but
      is rarely described as a cause of surgical site infections. We present the first
      reported case of Brucella melitensis causing sternal osteomyelitis of a midline
      sternotomy for a coronary artery bypass graft. The operation was performed in a
      non-endemic country but the patient had travelled to Syria immediately before
      surgery, where the infection was assumed to have been acquired. The infection
      resolved following treatment with doxycycline, rifampicin and gentamicin. We
      review the literature for surgical site infections related to Brucella species
      and discuss the infection control implications. Human brucellosis has the
      potential to cause surgical site infections and it should be in the differential
      diagnosis of any patient with a relevant exposure history presenting with a
      febrile illness and musculoskeletal findings. 

PMID- 24910375
TI  - Mechanoresponses of human primary osteoblasts grown on carbon nanotubes.
AB  - Bone mechanotransduction is strongly influenced by the biomaterial properties. A
      good understanding of these mechanosensory mechanisms in bone has the potential
      to provide new strategies in the highly evolving field of bone tissue
      engineering. The aim of the present investigation was to study the interactive
      effects of local mechanical stimuli on multiwalled carbon nanotubes
      (MWCNTs)/osteoblast interface, using an in vitro model that allows the study of
      cell growth, attachment and differentiation. Strain was applied at physiological
      levels [strain magnitudes 500 microstrain (MUE), at frequency of load application
      0.5 Hz]. The effect of mechanical strain and substrate was thus studied by
      measuring the messenger RNA expression of alkaline phosphatase, vinculin,
      collagen 1A, and integrins beta1, beta3, alpha4, and alphav, using real-time
      quantitative polymerase chain reaction. The osteoblasts grown on MWCNTs displayed
      quick adaptation to the new environment by modulating the expression of key
      adhesion integrins. Furthermore, the addition of mechanical strain interplayed
      with the extracellular matrix and was efficiently transduced by cells grown on
      MWCNTs, providing stronger adhesion and survival. MWCNTs are therefore a material
      perfectly compatible with osteoblast differentiation, adhesion, and growth, and
      should be further evaluated, to derive new-generation biomaterial scaffolds for
      the treatment of skeletal defects which require bone reconstruction.

PMID- 24910376
TI  - Prevalence of drug resistant epilepsy in adults with epilepsy attending a
      neurology clinic of a tertiary referral hospital in Singapore.
AB  - PURPOSE: To determine the proportion of population of adult people with epilepsy
      (PWE) in Singapore, who suffer from drug resistant epilepsy (DRE). METHODS: All
      adult PWE who had attended the neurology specialist clinic of a tertiary referral
      hospital in Singapore were profiled for drug responses according to the
      definition for DRE as specified by the International League against Epilepsy
      (ILAE) 2010 consensus. This is a retrospective cohort study. Data collected
      included demographics, characteristics of seizure and epilepsy, blood
      biochemistry levels, electroencephalogram and brain imaging findings, and
      medication histories. The types and dosages of antiepileptic drugs (AEDs) used
      were retrieved from case notes and checked against pharmacy records. Each patient
      was counselled upon the diagnosis of epilepsy and taught to maintain a seizure
      diary. The dates and number of seizures were retrieved from these diaries at each
      visit. Treatment-related adverse effects were routinely assessed and hence,
      patients were assumed to not have treatment-related adverse effects when no
      relevant documentation was encountered. RESULTS: The prevalence rate of DRE in
      this clinic was 21.5%, while 40.9% of PWE were drug responsive/seizure free at
      the point prevalence day (n=557). From multivariate analysis, patients with
      structural-metabolic aetiology [odds ratio (OR) 1.78, 95% confidence interval
      (CI) 1.003-3.148], mental retardation [OR 2.51, 95% CI 1.073-5.863], psychiatric
      illnesses [OR 3.349, 95% CI 1.181-9.501] and pre-treatment seizure frequency of
      more than once monthly [OR 2.775, 95% CI 1.190-6.469] were found to be more
      likely to have DRE (p<=0.05). Although the influence of Indian ethnicity on the
      risk of DRE was only found in the univariate analysis, it warrants investigation
      in a larger cohort. CONCLUSION: The findings may aid policy makers in designing
      treatment guidelines and allocating resources around PWE, with careful
      considerations that at any given time, 1 in 5 PWE have DRE.

PMID- 24910377
TI  - Reply: To PMID 24757133.

PMID- 24910378
TI  - Vitamin d levels affect outcome in pediatric hematopoietic stem cell
      transplantation.
AB  - The importance of vitamin D in immunologic processes has recently emerged, but
      whether it has any impact on the course of allogeneic hematopoietic stem cell
      transplantation (HSCT) has not been determined. Reports indicate that HSCT
      recipients, particularly children, often suffer from vitamin D deficiency. This
      study investigated the role of vitamin D in 123 children undergoing HSCT from
      2004 to 2011. Vitamin D (ie, serum calcidiol) was analyzed in collected
      cryostored samples. Patients were grouped according to pre-HSCT calcidiol level:
      insufficient (<50 nm/L, n = 38) and sufficient (>=50 nm/L, n = 85). Older
      children who underwent transplants from January through June and children of
      Middle Eastern or African origin were more commonly found in the insufficient
      group. Acute grades II to IV graft-versus-host disease occurred more frequently
      in the vitamin D sufficient group (47% versus 30%, P = .05), whereas no
      difference was demonstrated for chronic graft-versus-host disease. The neutrophil
      granulocytes rose significantly faster in the vitamin D sufficient group. No
      difference in lymphocyte counts, immunoglobulin levels, or infectious disease
      burden during the first year post-HSCT were observed. Among children with
      malignancies, overall survival was significantly better in the sufficient group
      (87% versus 50%, P = .01). In addition, rejection (0% versus 11%, P = .06) and
      relapse (4% versus 33%, P = .03) rates were lower in patients with sufficient
      vitamin D levels. To conclude, vitamin D may have an important impact on the
      outcome of pediatric HSCT, particularly in patients with malignant disease.
      Further studies investigating whether vitamin D acts as an immunomodulator or is
      merely a surrogate marker of patient health or nutritional status are warranted. 

PMID- 24910379
TI  - Unmanipulated haploidentical transplants compared with other alternative donors
      and matched sibling grafts.
AB  - We studied 459 consecutive patients with hematologic malignancies, median age 44
      years (range, 15 to 71 years), who underwent transplantation with grafts from
      identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43),
      mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105)
      or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease
      (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB
      recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and
      post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the
      HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced
      disease phase was more frequent, but not significantly so, in the HAPLO and mmUD
      groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the
      HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD
      (42%) groups (P < .001), and there was a trend toward less moderate-severe
      chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients
      off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO
      group (P < .001). Transplantation-related mortality at 2 years was lower in the
      HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups
      (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The
      4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in
      the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In
      multivariate analysis, advanced disease was a negative predictor of survival
      (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia
      (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB
      had inferior survival (P = .03). In conclusion, unmanipulated haploidentical
      family donor transplants are an additional option for patients lacking a matched
      sibling donor. 

PMID- 24910381
TI  - Alemtuzumab for severe steroid-refractory gastrointestinal acute graft-versus
      host disease.
AB  - Acute graft-versus-host disease (aGVHD) still remains the main cause of morbidity
      and mortality after allogeneic stem cell transplantation. Moreover, patients who
      did not respond to first-line treatment with glucocorticosteroids have a very
      poor outcome. Some studies suggested that alemtuzumab (a humanized monoclonal
      antibody against the CD52 antigen) might be effective for treatment of refractory
      aGVHD. Here we report a single-center experience with alemtuzumab in refractory
      gastrointestinal aGVHD. From September 2009 to April 2012 at the Grenoble medical
      university center, 24 patients who had presented a refractory gastrointestinal
      aGVHD to corticosteroid, or after another immunosuppressive drug, were
      retrospectively analyzed. Most patients (n = 19) presented stage 4
      gastrointestinal aGVHD. Response to treatment (either complete or partial) was
      observed in 15 patients (62.4%). The overall survival rate at 1 year for all
      patients was 33.3% (95% confidence interval [CI], 15.9% to 51.9%) and for
      responders, 53.3% (95% CI, 26.3% to 74.4%). Two patients died from infection, 5
      patients from recurrent GVHD, and 1 from an uncontrolled post-transplant
      lymphoproliferative disorder. 

PMID- 24910380
TI  - Exercise and stress management training prior to hematopoietic cell
      transplantation: Blood and Marrow Transplant Clinical Trials Network (BMT CTN)
      0902.
AB  - Studies show that engaging patients in exercise and/or stress management
      techniques during hematopoietic cell transplantation (HCT) improves quality of
      life. The Blood and Marrow Transplant Clinical Trials Network tested the efficacy
      of training patients to engage in self-directed exercise and stress management
      during HCT. The study randomized 711 patients at 21 centers to receive 1 of 4
      training interventions before HCT: a self-directed exercise program, a self
      administered stress management program, both, or neither. Participants completed
      self-reported assessments at enrollment and up to 180 days after HCT.
      Randomization was stratified by center and transplant type. There were no
      differences in the primary endpoints of the Physical Component Summary and Mental
      Component Summary scales of the Medical Outcomes Study Short Form 36 at day +100
      among the groups, based on an intention-to-treat analysis. There also were no
      differences in overall survival, days of hospitalization through day +100 post
      HCT, or in other patient-reported outcomes, including treatment-related distress,
      sleep quality, pain, and nausea. Patients randomized to training in stress
      management reported more use of those techniques, but patients randomized to
      training in exercise did not report more physical activity. Although other
      studies have reported efficacy of more intensive interventions, brief training in
      an easy-to-disseminate format for either self-directed exercise or stress
      management was not effective in our trial. 

PMID- 24910382
TI  - Outcome of allogeneic stem cell transplantation for patients transformed to
      myelodysplastic syndrome or leukemia from severe aplastic anemia: a report from
      the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe
      Aplastic Anemia Working Party of the European Group for Blood and Marrow
      Transplantation.
AB  - One hundred and forty patients who had undergone hematopoietic stem cell
      transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous
      leukemia (AML) transformation after treatment of severe aplastic anemia (SAA)
      were identified in the European Group for Blood and Marrow Transplantation (EBMT)
      database. The median age at HSCT was 29 years (range, 1 to 66 years). The
      transplant donor was related in 49% cases and unrelated in 51% cases. The 5-year
      probability of relapse was 17%, and that of nonrelapse mortality was 41%. The 5
      year overall survival was 45% +/- 9%, better for patients untreated and patients
      in remission compared with patients with refractory disease. Our data indicate
      that allogeneic HSCT leads to prolonged survival in close to one-half of the
      patients transforming to MDS or AML from SAA. 

PMID- 24910383
TI  - Evaluation of TNF-alpha serum level in patients with recalcitrant multiple common
      warts, treated by lipid garlic extract.
AB  - No universal consensus about optimal modality for treating the recalcitrant
      multiple common warts (RMCW). The objective of the study was to evaluate the
      immunological mechanisms and clinical therapeutic effect of using lipid garlic
      extract (LGE) in the treatment of RMCW. The study included 50 patients with RMCW.
      They were randomly assigned into two groups: the first group (25 patients)
      received LGE, and the second group (25 patients) received saline as a control
      group. In both groups, treatments were made to single lesions, or largest wart in
      case of multiple lesions, until complete clearance of lesions or for a maximum of
      4 weeks. Blood serum was taken at pre-study and at the fourth week to measure
      tumor necrosis factor alpha (TNF-alpha) level. A significant difference was found
      between the therapeutic responses of RMCW to LGE antigen and saline control group
      (p < 0.001). In the LGE group, complete response was achieved in 96% of patients
      presenting with RMCW. There was a statistically nonsignificant increase in TNF
      alpha of LGE group versus saline group. No recurrence was observed in the LGE
      group. LGE as an immunotherapy is an inexpensive, effective, and safe modality
      with good cure rates for treatment of RMCWs, when other topical or physical
      therapies have failed. 

PMID- 24910384
TI  - Cell carriers to attack glioma.

PMID- 24910385
TI  - Long-term effects of cryopreservation on clinically prepared hematopoietic
      progenitor cell products.
AB  - BACKGROUND AIMS: The question of how long hematopoietic progenitor cells (HPCs)
      destined for clinical applications withstand long-term cryopreservation remains
      unanswered. To increase our basic understanding about the stability of HPC
      products over time, this study focused on characterizing long-term effects of
      cryopreservation on clinically prepared HPC products. METHODS: Cryovials (n =
      233) frozen for an average of 6.3 +/- 14.2 years (range, 0.003-14.6 years) from
      HPC products (n = 170) representing 75 individual patients were thawed and
      evaluated for total nucleated cells (TNCs), cell viability, viable CD34+ (vCD34+)
      cells and colony-forming cells (CFCs). TNCs were determined by use of an
      automated cell counter, and cell viability was measured with the use of trypan
      blue exclusion. Viable CD34 analysis was performed by means of flow cytometry and
      function by a CFC assay. RESULTS: Significant losses in TNCs, cell viability,
      vCD34+ cells and CFC occurred on cryopreservation. However, once frozen, viable
      TNCs, vCD34+ cells and CFC recoveries did not significantly change over time. The
      only parameter demonstrating a change over time was cell viability, which
      decreased as the length of time that an HPC product was stored frozen increased.
      A significant negative correlation (correlation coefficient = -0.165) was
      determined between pre-freeze percent granulocyte content and post-thaw percent
      viability (n = 170; P = 0.032). However, a significant positive correlation was
      observed between percent viability at thaw and pre-freeze lymphocyte
      concentration. CONCLUSIONS: Once frozen, HPC products were stable for up to 14.6
      years at <-150 degrees C. Post-thaw viability was found to correlate negatively
      with pre-freeze granulocyte content and positively with pre-freeze lymphocyte
      content.

PMID- 24910386
TI  - Ischaemic scalp ulceration and hair loss.

PMID- 24910387
TI  - Comparing recurrent antibiotic prescriptions in children treated with a brand
      name or a generic formulation.
AB  - PURPOSE: The aim of this study was to investigate the rate of recurrent
      prescriptions and hospital admissions in children receiving a brand name or
      generic antibiotic prescription. METHODS: The data source was a database of
      reimbursed prescriptions. Outpatient children/adolescents <18 years old (Lombardy
      Region, Italy) were included. The observational period was February-April 2010. A
      recurrence was defined as an antibiotic prescription occurring within 28 days
      after an index prescription. The rate of recurrent prescriptions and hospital
      admissions was calculated for generic/brand name formulations and for each age
      strata (0-5, 6-11, and 12-17 years old) for four antibiotics: amoxicillin,
      amoxicillin clavulanate, clarithromycin, and cefaclor. The percentage of therapy
      switches was calculated. Cochran-Mantel-Haenszel test was used to compare the age
      adjusted outcomes. RESULTS: In all, 17.5% (57 346) of children received at least
      one recurrent prescription. The rate of recurrent prescriptions was slightly
      lower in children receiving any generic (OR 0.96; 95%CI 0.93-0.98), compared with
      any brand name, antibiotic. The percentage of hospital admissions occurring in
      children initially treated with a brand name (1.01%; 95%CI 0.98-1.08) or generic
      (1.03%; 0.96-1.06) antibiotic was not different (p = 0.43). For children
      receiving amoxicillin clavulanate, the hospital admission rate was slightly
      higher in the brand name group (p = 0.002), while no differences were found for
      the other active substances. CONCLUSIONS: Children treated with generic
      antibiotics had no worse safety and effectiveness outcomes when compared with
      those receiving brand name ones. These results provide additional evidence on the
      safety of generic antibiotics.

PMID- 24910388
TI  - Drug resistance to targeted therapies: deja vu all over again.
AB  - A major limitation of targeted anticancer therapies is intrinsic or acquired
      resistance. This review emphasizes similarities in the mechanisms of resistance
      to endocrine therapies in breast cancer and those seen with the new generation of
      targeted cancer therapeutics. Resistance to single-agent cancer therapeutics is
      frequently the result of reactivation of the signaling pathway, indicating that a
      major limitation of targeted agents lies in their inability to fully block the
      cancer-relevant signaling pathway. The development of mechanism-based
      combinations of targeted therapies together with non-invasive molecular disease
      monitoring is a logical way forward to delay and ultimately overcome drug
      resistance development. 

PMID- 24910389
TI  - Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis.
AB  - SLUG represses E-cadherin to promote epithelial-mesenchymal transition (EMT) in
      various cancers. Mechanisms that regulate SLUG/E-cadherin pathway remain poorly
      understood, especially during tumorigenesis in vivo. Here we report that p19(Arf)
      (p14(ARF) in human) stabilizes Slug to inhibit E-cadherin in prostate cancer
      mouse models. Inactivation of p19(Arf) reduces Slug levels, resulting in
      increased E-cadherin expression and delaying the onset and progression of
      prostate cancer in Pten/Trp53 double null mice. Mechanistically, p14(ARF)
      stabilizes SLUG through increased sumoylation at lysine residue 192. Importantly,
      levels of SLUG and p14(ARF) are positively correlated in human prostate cancer
      specimens. These data demonstrated that ARF modulates the SLUG/E-cadherin
      signaling axis for augmenting prostate tumorigenesis in vivo, revealing a novel
      paradigm where the oncogenic functions of SLUG require ARF to target E-cadherin
      in prostate cancer. Collectively, our findings further support that ARF has dual
      tumor suppressive/oncogenic roles in cancers in a context-dependent manner.

PMID- 24910390
TI  - Homozygous TREM2 mutation in a family with atypical frontotemporal dementia.
AB  - TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal
      recessive disease characterized by recurrent fractures because of bone cysts and
      presenile dementia. Recently, homozygous and compound heterozygous TREM2
      mutations were identified in rare families with frontotemporal lobar degeneration
      (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous
      mutation in a new consanguineous Italian family. Two sibs had early onset
      autosomal recessive FTLD without severe bone disorders. Atypical signs were
      present in this family: early parietal and hippocampus involvement, parkinsonism,
      epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This
      study further demonstrates the implication of TREM2 mutations in FTLD phenotypes.
      It illustrates the variability of bone phenotype and underlines the frequency of
      atypical signs in TREM2 carriers. This and previous studies evidence that TREM2
      mutation screening should be limited to autosomal recessive FTLD with atypical
      phenotypes characterized by: (1) a very young age at onset (20-50 years); (2)
      early parietal and hippocampal deficits; (3) the presence of seizures and
      parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum
      thickness on brain magnetic resonance imaging.

PMID- 24910391
TI  - Use of diuretics is associated with reduced risk of Alzheimer's disease: the
      Cache County Study.
AB  - Although the use of antihypertensive medications has been associated with reduced
      risk of Alzheimer's disease (AD), it remains unclear which class provides the
      most benefit. The Cache County Study of Memory Health and Aging is a prospective
      longitudinal cohort study of dementing illnesses among the elderly population of
      Cache County, Utah. Using waves I to IV data of the Cache County Study, 3417
      participants had a mean of 7.1 years of follow-up. Time-varying use of
      antihypertensive medications including different class of diuretics, angiotensin
      converting enzyme inhibitors, beta-blockers, and calcium channel blockers was
      used to predict the incidence of AD using Cox proportional hazards analyses.
      During follow-up, 325 AD cases were ascertained with a total of 23,590 person
      years. Use of any antihypertensive medication was associated with lower incidence
      of AD (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.61
      0.97). Among different classes of antihypertensive medications, thiazide (aHR,
      0.7; 95% CI, 0.53-0.93), and potassium-sparing diuretics (aHR, 0.69; 95% CI, 0.48
      0.99) were associated with the greatest reduction of AD risk. Thiazide and
      potassium-sparing diuretics were associated with decreased risk of AD. The
      inverse association of potassium-sparing diuretics confirms an earlier finding in
      this cohort, now with longer follow-up, and merits further investigation.

PMID- 24910392
TI  - Aging in deep gray matter and white matter revealed by diffusional kurtosis
      imaging.
AB  - Diffusion tensor imaging has already been extensively used to probe
      microstructural alterations in white matter tracts, and scarcely, in deep gray
      matter. However, results in literature regarding age-related degenerative
      mechanisms in white matter tracts and parametric changes in the putamen are
      inconsistent. Diffusional kurtosis imaging is a mathematical extension of
      diffusion tensor imaging, which could more comprehensively mirror microstructure,
      particularly in isotropic tissues such as gray matter. In this study, we used the
      diffusional kurtosis imaging method and a white-matter model that provided
      metrics of explicit neurobiological interpretations in healthy participants (58
      in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions
      of-interest (anterior and posterior limbs of the internal capsule, cerebral
      peduncle, fornix, genu and splenium of corpus callosum, globus pallidus,
      substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses
      were performed to examine parametric differences across regions and correlations
      with age. In white matter tracts, evidence was found supportive for anterior
      posterior gradient and not completely supportive for retrogenesis theory. Age
      related degenerations appeared to be broadly driven by axonal loss. Demyelination
      may also be a major driving mechanism, although confined to the anterior brain.
      In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in
      the globus pallidus, substantia nigra, and red nucleus reflected higher
      microstructural complexity and directionality compared with the putamen, caudate
      nucleus, and thalamus. In particular, the unique age-related positive
      correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the
      putamen opposite to those in other regions call for further investigation of
      exact underlying mechanisms. In summary, the results suggested that diffusional
      kurtosis can provide measurements in a new dimension that were complementary to
      diffusivity metrics. Kurtosis together with diffusivity can more comprehensively
      characterize microstructural compositions and age-related changes than
      diffusivity alone. Combined with proper model, it may also assist in providing
      neurobiological interpretations of the identified alterations.

PMID- 24910393
TI  - Amyloid-beta diurnal pattern: possible role of sleep in Alzheimer's disease
      pathogenesis.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive cognitive decline that is a growing public health crisis with a
      prevalence projected to more than double in the next 20 years. Sleep is
      frequently impaired in individuals with AD. Further, recent studies have linked
      numerous age-related sleep disturbances such as poor sleep efficiency and sleep
      apnea, to future risk of cognitive impairment. Aggregation of amyloid-beta
      (Abeta) into extracellular plaques in the brain is a key step in AD pathogenesis
      and likely begins 20 years before the onset of dementia. Abeta concentrations in
      both humans and mouse models show Abeta concentrations rise during wakefulness
      and fall during sleep, that is, an Abeta diurnal pattern. There is evidence in
      animal models that changes in sleep time alter Abeta deposition, suggesting that
      sleep may play a role in AD pathogenesis. A hypothetical model for the role of
      sleep and the Abeta diurnal pattern in AD pathogenesis is proposed. 

PMID- 24910395
TI  - Overweight and high-sensitivity C-reactive protein are weakly associated with
      kidney stone formation in Japanese men.
AB  - OBJECTIVES: To investigate longitudinal relationships between
      obesity/inflammation and kidney stone formation in a population where obesity is
      not prevalent. METHODS: Using Cox regression models, associations between kidney
      stone formation and body mass index, waist circumference, high-sensitivity C
      reactive protein and other possible risk factors were retrospectively examined in
      a health screening Japanese population including 1726 men and 992 women. RESULTS:
      During 4 years of follow up (mean 3.2 years), kidney stones were formed in 238
      men (34.5 per 1000 person-years) and 82 women (20.7 per 1000 person-years). In
      men, when the possible risk factors were separately examined as continuous
      parameters, body mass index (P = 0.030) and waist circumference (P = 0.025) were
      significantly, and log C-reactive protein (P = 0.092) were marginally, associated
      with kidney stone formation. However, none of these parameters was independently
      associated with kidney stone formation after fully adjusted. In women, none of
      the aforementioned three parameters was associated with kidney stone formation.
      As a categorical parameter, the higher two quintiles of C-reactive protein were
      significantly associated with kidney stone formation compared with the lower two
      quintiles in men (P = 0.026). CONCLUSIONS: Overweight and C-reactive protein are
      weakly associated with kidney stone formation in Japanese men. Inflammation might
      be an underlying mechanism of the association between obesity and kidney stone
      formation.

PMID- 24910396
TI  - Different behavioral effect dose-response profiles in mice exposed to two-carbon
      chlorinated hydrocarbons: influence of structural and physical properties.
AB  - The present study aimed to clarify whether dose-response profiles of acute
      behavioral effects of 1,2-dichloroethane (DCE), 1,1,1-trichloroethane (TCE),
      trichloroethylene (TRIC), and tetrachloroethylene (PERC) differ. A test battery
      involving 6 behavioral endpoints was applied to evaluate the effects of DCE, TCE,
      TRIC, and PERC in male ICR strain mice under the same experimental conditions.
      The behavioral effect dose-response profiles of these compounds differed.
      Regression analysis was used to evaluate the relationship between the dose
      response profiles and structural and physical properties of the compounds. Dose
      response profile differences correlated significantly with differences in
      specific structural and physical properties. These results suggest that
      differences in specific structural and physical properties of DCE, TCE, TRIC, and
      PERC are responsible for differences in behavioral effects that lead to a variety
      of dose-response profiles. 

PMID- 24910397
TI  - A strategy utilizing a recyclable macrocycle transporter for the efficient
      synthesis of a triazolium-based [2]rotaxane.
AB  - A general synthesis of triazolium-containing [2]rotaxanes, which could not be
      accessed by other methods, is reported. It is based on a sequential strategy
      starting from a well-designed macrocycle transporter which contains a template
      for dibenzo-24-crown-8 and a N-hydroxysuccinimide (NHS) moiety. The sequence is:
      1) synthesis by slippage of a [2]rotaxane building-block; 2) its elongation at
      its NHS end; 3) the delivery of the macrocycle to the elongated part of the axle
      by an induced translational motion; 4) the contraction process to yield the
      targeted [2]rotaxane and recycle the initial transporter.

PMID- 24910398
TI  - Age and gender influence the cardiorespiratory function and metabolic rate of
      broiler chicks during normocapnia and hypercapnia.
AB  - Pulmonary ventilation (V(E)), body temperature (Tb), mean arterial pressure
      (MAP), heart rate (f(H)) and metabolic rate (V(O2)) were measured in 10 (d10)-
      and 21 (d21)-day-old male and female chicks exposed to 7% CO2. Under normocapnia,
      V(E) was higher in d10 chicks than in d21 due to a higher tidal volume; in
      females a higher respiratory frequency (f(R)) was also observed. The d10 birds
      presented higher f(H) and V(O2). The d21 females showed the highest CO2
      ventilatory response due to increased f(R). MAP did not change during hypercapnia
      while a hypercapnic bradycardia occurred, except in d21 females. Hypercapnia
      induced a drop in Tb in all groups and an increase in V(O2) in d21 males.
      Overall, no gender effect is observed in cardiorespiratory and metabolic
      variables in d10 and d21 chicks under normocapnia, the differences in V(E) and
      f(H) between ages may be related to distinct metabolic demands of these phases.
      The d21 female chicks seem to be more sensitive to hypercapnia.

PMID- 24910399
TI  - Knee joint stabilization therapy in patients with osteoarthritis of the knee and
      knee instability: subgroup analyses in a randomized, controlled trial.
AB  - OBJECTIVE: To test whether knee stabilization therapy, prior to
      strength/functional training, may have added value in reducing activity
      limitations only in patients with knee osteoarthritis who have knee instability
      and (i) low upper leg muscle strength, (ii) impaired knee proprioception, (iii)
      high knee laxity, or (iv) frequent episodes of knee instability. DESIGN: Subgroup
      analyses in a randomized controlled trial comparing 2 exercise programmes
      (with/without knee stabilization therapy) (STABILITY; NTR1475). PATIENTS:
      Participants from the STABILITY-trial with clinical knee osteoarthritis and knee
      instability (n = 159). METHODS: Effect modification by upper leg muscle strength,
      knee proprioception, knee laxity, and patient-reported knee instability were
      determined using the interaction terms "treatment group subgroup factor", with
      the outcome measures WOMAC physical function (primary), numeric rating scale pain
      and the Get up and Go test (secondary). RESULTS: Effect modification by muscle
      strength was found for the primary outcome (p = 0.01), indicating that patients
      with greater muscle strength tend to benefit more from the experimental programme
      with additional knee stabilization training, while patients with lower muscle
      strength benefit more from the control programme. CONCLUSION: Knee stabilization
      therapy may have added value in patients with instability and strong muscles.
      Thus it may be beneficial if exercises target muscle strength prior to knee
      stabilization.

PMID- 24910400
TI  - Improving 2-phenylethanol and 6-pentyl-alpha-pyrone production with fungi by
      microparticle-enhanced cultivation (MPEC).
AB  - Trichoderma atroviride IMI 206040 synthesizes the coconut lactone 6-pentyl-alpha
      pyrone (6-PAP) de novo and Aspergillus niger DSM 821 produces the rose-like
      flavour compound 2-phenylethanol (2-PE) from the precursor l-phenylalanine. Here,
      microparticles of different chemical composition and nominal particle diameter in
      the range 5-250 um were added to shake-flask cultures of both fungi to
      investigate the particles' effect on product formation. Maximum 2-PE
      concentration increased by a factor of 1.3 to 1430 mg/l with the addition of 2%
      w/v talc (40 um diameter). Maximum 6-PAP concentration increased by a factor of 2
      to 40 mg/l with the addition of 2% w/v iron (II, III) oxide. The influence of
      ions leaching out of the particles was investigated by cultivating the fungi in
      leached particle medium. For the first time, the positive effect of the
      microparticle-enhanced cultivation (MPEC) technique on the microbial production
      of volatile metabolites, here flavour compounds from submerged fungal cultures,
      is demonstrated. The effect is strain- and particle-specific.

PMID- 24910401
TI  - Examination of national lymph node evaluation practices for adult extremity soft
      tissue sarcoma.
AB  - BACKGROUND AND OBJECTIVES: Lymph node evaluation recommendations for extremity
      soft tissue sarcoma (ESTS) are absent from national guidelines. Our objectives
      were (1) to assess rates and predictors of nodal evaluation, and (2) to assess
      rates and predictors of nodal metastases. METHODS: ESTS patients from the
      National Cancer Data Base (2000-2009) were assessed, and regression models were
      used to identify factors associated with nodal evaluation and metastases.
      RESULTS: Of 27,536 ESTS patients, 1,924 (7%) underwent nodal evaluation, and of
      these, 290 (15%) had nodal metastases. Nodal evaluation was most frequently
      performed for rhabdomyosarcoma (15.6%), angiosarcoma (10.0%), clear cell sarcoma
      (39.3%), epithelioid sarcoma (28.1%), and synovial sarcoma (9.3%). On
      multivariable analysis, factors associated with nodal evaluation included
      histologic subtype, tumor size, and grade. Nodal metastasis rates were highest
      among patients with rhabdomyosarcoma (32.1%), angiosarcoma (24.1%), clear cell
      sarcoma (27.7%), and epithelioid sarcoma (31.8%). On multivariable analysis,
      factors associated with nodal metastases included histologic subtype, tumor size,
      and grade. CONCLUSIONS: Nodal evaluation rates are highest among certain expected
      subtypes but are generally low. However, nodal metastasis rates for many
      histologic subtypes in patients selected for lymph node evaluation may be higher
      than previously reported. Multi-institutional studies should address nodal
      evaluation for ESTS.

PMID- 24910402
TI  - [Orbital neurenteric cyst. A case report and review of the literature].
AB  - INTRODUCTION: Neurenteric cysts defined as a cyst lined by endodermal-type
      epithelium are extremely rare. We report a rare case of an orbital neurenteric
      cyst. CASE REPORT: A 19-year-old female presented with an orbital cyst tumor that
      had cosmetic consequences. The signal of the cyst was not enhanced after
      administration of gadolinium on MRI examination. The patient underwent surgery
      due to the increase in size of the tumor. A complete cyst removal including the
      cyst wall through the inferior palpebral fold was performed. The histological
      examination confirmed the diagnostic of neurenteric cyst. The patient was
      discharged home in excellent condition. CONCLUSION: This report discusses the
      clinical presentation, neuroradiological aspect, pathological findings and
      therapeutic consideration of the neurenteric cyst. We described a rare case of
      orbital neurenteric cyst. Due to the local recurrence rate observed after partial
      resection, the goal of the surgery should be a total resection of the cyst with
      the cyst wall.

PMID- 24910403
TI  - Metal-induced self-assembly of peroxiredoxin as a tool for sorting ultrasmall
      gold nanoparticles into one-dimensional clusters.
AB  - Nanomanipulation of matter to create responsive, ordered materials still remains
      extremely challenging. Supramolecular chemistry has inspired new strategies by
      which such nanomaterials can be synthesized step by step by exploiting the self
      recognition properties of molecules. In this work, the ring-shaped architecture
      of the 2-Cys peroxiredoxin I protein from Schistosoma mansoni, engineered to have
      metal ion-binding sites, is used as a template to build up 1D nanoscopic
      structures through metal-induced self-assembly. Chromatographic and microscopic
      analyses demonstrate the ability of the protein rings to stack directionally upon
      interaction with divalent metal ions and form well-defined nanotubes by
      exploiting the intrinsic recognition properties of the ring surfaces. Taking
      advantage of such behavior, the rings are then used to capture colloidal Ni(2+)
      functionalized ultrasmall gold nanoparticles and arrange them into 1D arrays
      through stacking into peapod-like complexes. Finally, as the formation of such
      nano-peapods strictly depends on nanoparticle dimensions, the peroxiredoxin
      template is used as a colloidal cut-off device to sort by size the encapsulated
      nanoparticles. These results open up possibilities in developing Prx-based
      methods to synthesize new advanced functional materials. 

PMID- 24910404
TI  - Selective route to 2-propenyl aryls directly from wood by a tandem organosolv and
      palladium-catalysed transfer hydrogenolysis.
AB  - A tandem organosolv pulping and Pd-catalysed transfer hydrogenolysis
      depolymerisation and deoxygenation has been developed. The tandem process
      generated 2-methoxy-4-(prop-1-enyl)phenol in 23% yield (92% theoretical monomer
      yield) starting from pine wood and 2,6-dimethoxy-4-(prop-1-enyl)phenol in 49%
      yield (92% theoretical monomer yield) starting from birch wood. Only endogenous
      hydrogen from wood was consumed, and the reaction was performed using green
      solvents.

PMID- 24910405
TI  - Comparative pharmacokinetic investigation on baicalin and wogonoside in type 2
      diabetic and normal rats after oral administration of traditional Chinese
      medicine Huanglian Jiedu decoction.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu decoction (HLJDD) is used
      traditionally in China for the treatment of diabetes mellitus in clinical
      practice, which has been proved to be effective. The purpose of this study was to
      investigate the pharmacokinetic characteristics (especially the area under the
      curve, AUC) of baicalin and wogonoside in type 2 diabetic rats after oral
      administration of HLJDD extract and to explore its possible mechanism. MATERIALS
      AND METHODS: HLJDD extract and Radix scutellariae extract were prepared and the
      contents of baicalin and wogonoside contained in two extracts were assayed with
      high performance liquid chromatography (HPLC). Type 2 diabetic rats were induced
      by high fat diet and intraperitoneal injection of streptozotocin.
      Pharmacokinetics of baicalin and wogonoside in type 2 diabetic and normal control
      rats after oral administration of HLJDD extract or Radix scutellariae extract
      were investigated. Pharmacokinetics of baicalin in type 2 diabetic and normal
      rats after oral administration of pure baicalin was also investigated. RESULTS:
      The pharmacokinetic parameters (especially AUCs) of baicalin and wogonoside in
      type 2 diabetic rats after oral administration of HLJDD extract were remarkably
      different from those in normal rats. And the alterations of the AUCs of baicalin
      and wogonoside in type 2 diabetic rats after oral administration of Radix
      scutellariae extract were similar to those after oral administration of HLJDD
      extract. Moreover, the increase of the AUC of baicalin in type 2 diabetic rats
      after oral administration of pure baicalin was similar to that after oral
      administration of HLJDD extract or Radix scutellariae extract. CONCLUSION: The
      pharmacokinetic behaviors of baicalin and wogonoside (especially the systemic
      exposure [AUCs] of baicalin and wogonoside) were significantly altered in type 2
      diabetic rats after orally administrated HLJDD extract. And the increased AUCs of
      baicalin and wogonoside in type 2 diabetic rats after oral administration of
      HLJDD extract resulted from neither the effects of other herbs contained in HLJDD
      nor the effects of other components contained in Radix scutellariae. It might
      result from the effects of the pathological status of type 2 diabetes mellitus.

PMID- 24910406
TI  - Korean Scutellaria baicalensis Georgi methanol extracts inhibits metastasis via
      the Forkhead Box M1 activity in hepatocellular carcinoma cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi, commonly known as
      skullcaps, and it has been widely used as traditional therapeutic herb in several
      eastern Asia including Korea, China and Japan because of its remarkable anti
      inflammatory and anti-cancer effects. Our study focuses on the anti-metastatic
      effects of Scutellaria baicalensis Georgi in hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: Methanol extract of Scutellaria baicalensis Georgi was
      examined for identification of its composition by HPLC-MS/MS. The extract was
      evaluated for the anti-metastasis activity using HepG2 hepatocellular carcinoma
      cells via immunoblotting and RT-PCR. For mechanical study, specific Forkhead Box
      M1 (FOXM1) vector was transfected to HepG2 cells. RESULTS: Scutellaria
      baicalensis Georgi potentially inhibited proliferation of HepG2 cells dose
      dependently. Scutellaria baicalensis Georgi decreased metastasis through the
      regulation of matrix metalloproteinase 2 (MMP-2) and FOXM1 activities at the
      transcription and translation levels. CONCLUSIONS: The results of the present
      study suggest that Scutellaria baicalensis Georgi could be a potent
      chemotherapeutic agent against HCC. Its clinical use guarantee for further study
      and individual flavonoids from Scutellaria baicalensis Georgi should also be
      investigated.

PMID- 24910407
TI  - Ethnobotanical and phytomedical knowledge in the North-Western Ligurian Alps.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The ethnobotany of European alpine regions is
      much diversified and scarcely investigated. These regions retain a well-developed
      heritage culture and botanical traditional knowledge, favored by the isolated
      montane location. We carried out a study of therapeutic and traditional uses of
      native plants of a poorly explored area of the Western Italian Alps in the
      Ligurian region (NW Italy). The area has been the object of human activities
      since prehistoric ages, and an obliged crossroad for people moving across
      Provence, Liguria and Piemonte. METHODOLOGY: The investigation was conducted in
      the upper Tanarello and Arroscia Valleys by using semi-structured, open
      interviews. Data were summarized by different indices--Relative Frequency of
      Citation (RFC), Cultural Value Index (CV), Ethnobotanicity Index (EI) and
      Informant Consensus Factor (Fic). RESULTS AND DISCUSSION: A group of 65
      informants were interviewed, yielding an inventory of 199 botanical taxa from 64
      families, and a total of 2661 citations. A total of 13 categories of use were
      found, of which the most frequent ones were medicinal and food. In addition, 12
      main medicinal subcategories were recorded. Botanicals were mainly used to treat
      digestive system, respiratory system, and the skin. A relevant role was played by
      plants with digestive and remineralizing properties. On the basis of quantitative
      analysis (RFC and CV indices) among the 30 most relevant plants are included rare
      and/or protected species, such as Achillea ligustica, Arnica montana, Gentiana
      ligustica, Gentiana lutea, and Achillea erba-rotta. CONCLUSIONS: An exhaustive
      prospect of the ethnobotanical knowledge in North-Western Ligurian Alps has been
      achieved through the recording of a large number of data. About 50% of the
      recorded uses have survived in the area. A great traditional importance is
      retained by species such as Artemisia absinthium, Lavandula angustifolia and
      Arnica montana which were formerly cultivated and marketed for their therapeutic
      virtues. A substantial role is also attributable to the tree species Pinus sp.
      pl., Castanea sativa and Olea europaea that have been exploited as sources of
      wood/food since long ago. These plants are a natural resource deserving
      reevaluation among local agriculture and commercial activities.

PMID- 24910408
TI  - Reversing effects of lignans on CCl4-induced hepatic CYP450 down regulation by
      attenuating oxidative stress.
AB  - Oxidative stress has been proved to be a critical reason of regulating CYP450s
      under hepatic injury status. The study was aimed to investigate the effect of
      pretreatment of schisandra lignan extracts (SLE) and dimethyl diphenyl
      bicarboxylate (DDB) on expressions and activities of the main liver P450
      isoenzymes in CCl4 induced liver injury rats and their anti-oxidative effects on
      both CCl4 induced liver injury rats and a CCl4 induced HepG2 cell injury model.
      Acute experimental liver injury induced by CCl4 caused drastically decreasing
      activities of the main liver P450 isoenzymes such as CYP1A2, CYP2C6, CYP2E1 and
      CYP3A2, as well as their protein expressions. Pretreatment of SLE (500 mg/kg) and
      DDB (200 mg/kg) twice a day for three days significantly decreased the losses of
      activities of CYP1A2, CYP2C6, CYP2E1 and CYP3A2. Similar results were observed in
      protein expressions. In addition, in the CCl4 induced HepG2 cells injury model
      and the CYP3A activity level correlated well with ROS level in several
      ingredients of SLE treated groups, especially in gamma-schisandrin group. These
      results indicated that the reversion of P450 after SLE/DDB treatment were, on one
      hand, due to hepatoprotective effects of these lignans on livers; on the other
      hand, due to their regulation of P450 through anti-oxidative effect and gamma
      schisandrin might be the most powerful ingredient of SLE. Also, there might be
      potential interactions between SLE or DDB and co-administered medicines and it is
      necessary to adjust the dosage of co-administrated medicines in clinical
      medication of liver disease.

PMID- 24910409
TI  - Determination of preservatives in soft drinks by capillary electrophoresis with
      ionic liquids as the electrolyte additives.
AB  - A capillary electrophoresis method for separating preservatives with various
      ionic liquids as the electrolyte additives has been developed. The performances
      for separation of the preservatives using five ionic liquids with different
      anions and different substituted group numbers on imidazole ring were studied.
      After investigating the influence of the key parameters on the separation (the
      concentration of ionic liquids, pH, and the concentration of borax), it has been
      found that the separation efficiency could be improved obviously using the ionic
      liquids as the electrolyte additives and tested preservatives were baseline
      separated. The proposed capillary electrophoresis method exhibited favorable
      quantitative analysis property of the preservatives with good linearity (r(2) =
      0.998), repeatability (relative standard deviations <= 3.3%) and high recovery
      (79.4-117.5%). Furthermore, this feasible and efficient capillary electrophoresis
      method was applied in detecting the preservatives in soft drinks, introducing a
      new way for assaying the preservatives in food products. 

PMID- 24910410
TI  - Impact of denervation-induced muscle atrophy on housekeeping gene expression in
      mice.
AB  - INTRODUCTION: Immobilization induced by experimental denervation leads to rapid
      and progressive alterations in structural and biochemical properties of skeletal
      muscle. Real-time reverse transcription-polymerase chain reaction (RT-PCR) is a
      popular method of elucidating the molecular mechanisms involved in muscle
      atrophy. Identification of suitable reference genes that are not affected by
      experimental conditions is a critical step in accurate normalization of real-time
      RT-PCR. METHODS: We investigated the impact of denervation-induced muscle atrophy
      for 2 weeks on the expression of common housekeeping genes. RESULTS: Denervation
      differentially affected the expression levels of these genes. RefFinder software
      identified TATA box binding protein (Tbp) as the most stable gene and showed that
      the stability of glyceraldehyde-3-phosphate dehydrogenase (Gapdh) and
      hypoxanthine guanine phosphoribosyl transferase (Hprt) genes was low, even though
      they are widely used for normalization. CONCLUSIONS: The appropriate reference
      gene for normalization of genes of interest in denervated muscle is Tbp.

PMID- 24910412
TI  - Efficient refolding and immobilization of PMMA-tag-fused single-chain Fv
      antibodies for sensitive immunological detection on a PMMA plate.
AB  - In this study, we investigated the efficient refolding and site-specific
      immobilization of single-chain variable fragments (scFvs) genetically fused with
      a poly(methylmethacrylate)-binding peptide (PMMA-tag). According to the results
      of an aggregation test of a scFv-PM in the presence of 0.5 M urea, aggregation
      was hardly detectable at a weak-alkaline pH (8.5) with lower concentrations of
      NaCl. Consequently, more than 93% recovery of the anti-RNase scFv-PM model was
      attained, when it was refolded by dialysis against 50 mM TAPS (pH8.5). These
      results suggested that the apparent isoelectric point (pI) of a target scFv was
      decreased to a great extent by the genetic fusion of a PMMA-tag containing 5
      acidic amino acids, and, thus, the solubility of the scFv-PM in its semi
      denatured form was considerably improved. We also designed alternative peptide
      tags composed of plural aspartic acid residues (D5, D10 and D15-tags) to decrease
      the apparent pI value of the fusion protein. As a consequence, scFv-D5, scFv-D10
      and scFv-D15 were also efficiently refolded with yields of more than 95%. It is
      noteworthy that even scFv-PS-D15, which had both a positively charged polystyrene
      binding peptide (PS-tag) and a negatively charged D15-tag, was serially connected
      at the C-terminal region of scFvs, and also refolded with a yield of 96.1%. These
      results clearly indicate that controlling the apparent pI value of scFvs by the
      fusion of oligo-peptides composed of acidic amino acids at the C-terminus
      resulted in a high degree of recovery via dialysis refolding. According to the
      results of a sandwich ELISA using scFv-PMs, scFv-D15 and scFv-PS-D15 as ligands,
      high antigen-binding signals were detected from both the PMMA and phi-PS plates
      immobilized with scFv-PMs. Furthermore, the high antigen-binding activity of scFv
      PMs was maintained in an adsorption state when it was immobilized on the surface
      of not only PMMA, but also hydrophilic PS (phi-PS) and polycarbonate (PC). These
      results strongly suggested that a PMMA-tag introduced at the C-terminus of scFvs
      preferably recognizes ester and/or carboxyl groups exposed on the surface of
      plastics. The scFv-PM developed in the present study has advantages such as being
      a ligand antibody, compared with whole Ab and the conventional PS-tag-fused scFvs
      (scFv-PS), and, thus, it is considerably useful in a sandwich ELISA as well as in
      various immuno-detection and immuno-separation systems.

PMID- 24910411
TI  - The impact of Nucleofection(r) on the activation state of primary human CD4 T
      cells.
AB  - Gene transfer into primary human CD4 T lymphocytes is a critical tool in studying
      the mechanism of T cell-dependent immune responses and human immunodeficiency
      virus-1 (HIV-1) infection. Nucleofection(r) is an electroporation technique that
      allows efficient gene transfer into primary human CD4 T cells that are
      notoriously resistant to traditional electroporation. Despite its popularity in
      immunological research, careful characterization of its impact on the physiology
      of CD4 T cells has not been documented. Herein, using freshly-isolated primary
      human CD4 T cells, we examine the effects of Nucleofection(r) on CD4 T cell
      morphology, intracellular calcium levels, cell surface activation markers, and
      transcriptional activity. We find that immediately after Nucleofection(r), CD4 T
      cells undergo dramatic morphological changes characterized by wrinkled and
      dilated plasma membranes before recovering 1h later. The intracellular calcium
      level also increases after Nucleofection(r), peaking after 1h before recovering
      8h post transfection. Moreover, Nucleofection(r) leads to increased expression of
      T cell activation markers, CD154 and CD69, for more than 24h, and enhances the
      activation effects of phytohemagglutinin (PHA) stimulation. In addition,
      transcriptional activity is increased in the first 24h after Nucleofection(r),
      even in the absence of exogenous stimuli. Therefore, Nucleofection(r)
      significantly alters the activation state of primary human CD4 T cells. The
      effect of transferred gene products on CD4 T cell function by Nucleofection(r)
      should be assessed after sufficient resting time post transfection or analyzed in
      light of the activation caveats mentioned above.

PMID- 24910413
TI  - Introduction to a Special Issue of the Journal of Immunological Methods: Building
      global resource programs to support HIV/AIDS clinical trial studies.
AB  - This Special Issue of the Journal of Immunological Methods includes 16
      manuscripts describing quality assurance activities related to virologic and
      immunologic monitoring of six global laboratory resource programs that support
      international HIV/AIDS clinical trial studies: Collaboration for AIDS Vaccine
      Discovery (CAVD); Center for HIV/AIDS Vaccine Immunology (CHAVI); External
      Quality Assurance Program Oversight Laboratory (EQAPOL); HIV Vaccine Trial
      Network (HVTN); International AIDS Vaccine Initiative (IAVI); and Immunology
      Quality Assessment (IQA). The reports from these programs address the many
      components required to develop comprehensive quality control activities and
      subsequent quality assurance programs for immune monitoring in global clinical
      trials including: all aspects of processing, storing, and quality assessment of
      PBMC preparations used ubiquitously in HIV clinical trials, the development and
      optimization of assays for CD8 HIV responses and HIV neutralization, a
      comprehensive global HIV virus repository, and reports on the development and
      execution of novel external proficiency testing programs for immunophenotyping,
      intracellular cytokine staining, ELISPOT and luminex based cytokine measurements.
      In addition, there are articles describing the implementation of Good Clinical
      Laboratory Practices (GCLP) in a large quality assurance laboratory, the
      development of statistical methods specific for external proficiency testing
      assessment, a discussion on the ability to set objective thresholds for measuring
      rare events by flow cytometry, and finally, a manuscript which addresses a
      framework for the structured reporting of T cell immune function based assays. It
      is anticipated that this series of manuscripts covering a wide range of quality
      assurance activities associated with the conduct of global clinical trials will
      provide a resource for individuals and programs involved in improving the
      harmonization, standardization, accuracy, and sensitivity of virologic and
      immunologic testing. 

PMID- 24910415
TI  - Different cellular responses of dexmedetomidine at infected site and peripheral
      blood of emdotoxemic BALB/c mice.
AB  - Various sedative agents, including dexmedetomidine (dex), induce
      immunosuppression, and enhance infection progression. However, there was no
      information on how anesthetic affects local and systemic cellular immune
      function. We conducted this study to examine the impact of dex on the
      differentiation and function of immune cells at site of inflammation and in
      peripheral blood during endotoxemia of mice. In BALB/c mice with and without
      endotoxemia, we evaluated the influence of two dosages of 5 and 50 mcg/kg/h
      intravenous dex on immune cells: including number of T cells (CD3), B cells
      (CD19), natural killer cells (CD8a), monocytes (CD11b), and macrophages (Mac-3)
      in peripheral blood, the activities of macrophages in peripheral blood and in
      peritoneal lavage, and proliferation of B and T cells and of natural killer cells
      activity in the spleen. Endotoxemia increased the number of CD3 T cells, CD 19 B
      cells and macrophages in the peripheral blood, augmented macrophage activity in
      the peritoneum, and increased T cell proliferation and natural killer cell
      activity in the spleen. Further administration of 5 mcg/kg/h dex attenuated
      systemic increase in number of T cells, B cells, and macrophages during
      endotoxemia and 50 mcg/kg/h dex significantly attenuated the increase in activity
      of macrophages in the peripheral blood during endotoxemia. In the peritoneum,
      however, 5 mcg/kg/h dex preserved and 50 mcg/kg/h dexmedetomidine enhanced the
      activity of macrophages during endotoxemia. Increased in proliferation of T cells
      in spleen during endotoxemia was attenuated by both doses of dex. Last, 50
      mcg/kg/h dex enhanced natural killer cells activity during endotoxemia. While
      preserving the effects of endotoxemia on macrophage's activity in the infection
      site and natural killer cell's activity in the spleen, dex decreased systemic
      fulminant immune reaction in endotoxemia, by attenuating the augmented response
      in the number of T cells, B cells and macrophages, activity of macrophages in the
      peripheral blood, and proliferation of T cells in spleen during endotoxemia.

PMID- 24910414
TI  - The Center for HIV/AIDS Vaccine Immunology (CHAVI) multi-site quality assurance
      program for cryopreserved human peripheral blood mononuclear cells.
AB  - The Center for HIV/AIDS Vaccine Immunology (CHAVI) consortium was established to
      determine the host and virus factors associated with HIV transmission, infection
      and containment of virus replication, with the goal of advancing the development
      of an HIV protective vaccine. Studies to meet this goal required the use of
      cryopreserved Peripheral Blood Mononuclear Cell (PBMC) specimens, and therefore
      it was imperative that a quality assurance (QA) oversight program be developed to
      monitor PBMC samples obtained from study participants at multiple international
      sites. Nine site-affiliated laboratories in Africa and the USA collected and
      processed PBMCs, and cryopreserved PBMC were shipped to CHAVI repositories in
      Africa and the USA for long-term storage. A three-stage program was designed,
      based on Good Clinical Laboratory Practices (GCLP), to monitor PBMC integrity at
      each step of this process. The first stage evaluated the integrity of fresh PBMCs
      for initial viability, overall yield, and processing time at the site-affiliated
      laboratories (Stage 1); for the second stage, the repositories determined post
      thaw viability and cell recovery of cryopreserved PBMC, received from the site
      affiliated laboratories (Stage 2); the third stage assessed the long-term
      specimen storage at each repository (Stage 3). Overall, the CHAVI PBMC QA
      oversight program results highlight the relative importance of each of these
      stages to the ultimate goal of preserving specimen integrity from peripheral
      blood collection to long-term repository storage. 

PMID- 24910416
TI  - Significant survival impact of MACC1 polymorphisms in HER2 positive breast cancer
      patients.
AB  - BACKGROUND: Deregulation of hepatocyte growth factor (HGF)/mesenchymal-epithelial
      transition factor (MET) signalling has been associated with poor clinical outcome
      in breast cancer and other cancers. The recently discovered metastasis-associated
      in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway.
      Potential links between genetic variants of the MACC1 gene and survival in breast
      cancer patients are unknown. In the present study, we therefore aimed to
      investigate the influence of MACC1 polymorphisms on event-free and overall
      survival in patients with human epidermal growth factor 2 (HER2)-positive breast
      cancer. METHODS: The present study included 164 consecutive white patients with
      HER2-positive breast cancer. Three MACC1 polymorphisms, rs1990172, rs975263 and
      rs3735615, already associated with cancer prognosis or with potential functional
      effects, were genotyped by the 5' nuclease assay. RESULTS: Multivariate Cox
      regression analysis adjusted for age and tumour stage showed increased risk for
      progression or death for carriers of the rare allele (G-allele) of single
      nucleotide polymorphism (SNP) rs1990172 (hazard ratios (HR) = 2.26; p = 0.004 and
      HR = 3.13; p = 0.001 for event-free survival and overall survival, respectively).
      In addition, we were able to demonstrate an adverse effect on cancer prognosis
      for carriers of the rare allele (T-allele) of SNP rs975263 (HR = 2.17; p = 0.007
      and HR = 2.80; p = 0.003 for event-free survival and overall survival,
      respectively). The rare allele (C-allele) of SNP rs3735615 showed a significant
      protective impact on event-free survival as well as overall survival (HR = 0.25;
      p = 0.001, and HR = 0.16; p = 0.001, respectively). CONCLUSIONS: This study
      provides first evidence that MACC1 polymorphisms are associated with clinical
      outcome for HER2-positive breast cancer patients. Further studies are warranted
      to validate these findings.

PMID- 24910417
TI  - Actinomycin D, cisplatin, and etoposide regimen is associated with almost
      universal cure in patients with high-risk gestational trophoblastic neoplasia.
AB  - BACKGROUND: Patients with high-risk gestational trophoblastic neoplasia (GTN)
      need multi-agent chemotherapy to be cured. The most common regimen is etoposide
      (E), methotrexate (M) and actinomycin D (A), alternating weekly with
      cyclophosphamide (C) plus vincristine (O) (EMA/CO). Cisplatin (P) is a very
      active drug, but it is usually restricted to second-line therapies. Herein, we
      report the results of a cisplatin-based therapy: APE (actinomycin D, cisplatin,
      and etoposide). PATIENTS AND METHODS: The efficacy and safety of APE for high
      risk GTN (defined by Institut Gustave-Roussy (IGR) criteria and/or an
      International Federation of Gynaecology and Obstetrics (FIGO) score >6) are
      reported. Patients with brain metastasis or placental-site trophoblastic tumour
      were excluded. RESULTS: Between 1985 and 2013, 95 patients were treated with APE
      for high-risk GTN: 59 patients as first-line, 36 as ? 2nd-line therapy. There was
      94.7% complete remission, though five patients relapsed. One patient died from
      GTN after multiple lines of chemotherapy. The five-year overall survival rate
      (median follow-up 5.7 years) was 97% (95% confidence interval (CI): 91-99%). No
      death from toxicity occurred. Long-term, six grade-1 neuro-toxicities, three
      grade-1 and two grade-2 oto-toxicities, and one grade-1 renal toxicity were
      recorded. One patient developed AML-M4 after APE and EMA/CO. Thirty-four of 35
      women, who wished to become pregnant, succeeded and all had at least one live
      birth. CONCLUSION: With a 97% long-term overall survival rate, limited long-term
      toxicity, and an excellent reproductive outcome, APE could be regarded as an
      alternative option to EMA/CO as a standard therapy for high-risk GTN.

PMID- 24910418
TI  - The orexin type 1 receptor is overexpressed in advanced prostate cancer with a
      neuroendocrine differentiation, and mediates apoptosis.
AB  - AIM: In the present study, we have examined the presence of orexins and their
      receptors in prostate cancer (CaP) and investigated their effects on the
      apoptosis of prostate cancer cells. METHODS: We have localised the orexin type 1
      and 2 receptors (OX1R and OX2R) and orexin A (OxA) in CaP sections of various
      grades and we have quantified tumour cells containing OX1R. Expression of OX1R
      was evaluated in the androgeno-dependent (AD) LNCaP and the androgeno-independent
      (AI) DU145 prostate cancer cells submitted or not to a neuroendocrine
      differentiation. The effects of orexins on the apoptosis and viability of DU145
      cells were also investigated. RESULTS: OX1R is strongly expressed in
      carcinomatous foci exhibiting a neuroendocrine differentiation, and the number of
      OX1R-stained cancer cells increases with the grade of the CaP. In contrast, OX2R
      is only detected in scattered malignant cells in high grade CaP. OX1R is
      expressed in the AI DU145 cells but is undetectable in the LNCaP cells.
      Acquisition of a neuroendocrine phenotype by the DU145 cells is associated with
      an overexpression of OX1R. Orexins induce the apoptosis of DU145 cells submitted
      to a neuroendocrine differentiation. CONCLUSION: The present data indicate that
      OX1R-driven apoptosis is overexpressed in AI CaP exhibiting a neuroendocrine
      differentiation opening a gate for novel therapies for these aggressive cancers
      which are incurable until now.

PMID- 24910419
TI  - Dissolution of glass wool, rock wool and alkaline earth silicate wool:
      morphological and chemical changes in fibers.
AB  - The behavior of alkaline earth silicate (AES) wool and of other biosoluble wools
      in saline solution simulating physiological fluids was compared with that of a
      traditional wool belonging to synthetic vitreous fibers. Morphological and size
      changes of fibers were studied by scanning electron microscopy (SEM). The
      elements extracted from fibers were analyzed by inductively coupled plasma atomic
      emission spectrometry. SEM analysis showed a larger reduction of length-weighted
      geometric mean fiber diameter at 4.5 pH than at 7.4 pH. At the 7.4 pH, AES wool
      showed a higher dissolution rate and a dissolution time less than a few days.
      Their dissolution was highly non-congruent with rapid leaching of calcium. Unlike
      rock wool, glass wool dissolved more rapidly at physiological pH than at acid pH.
      Dissolution of AES and biosoluble rock wool is accompanied by a noticeable change
      in morphology while by no change for glass wool. Biosoluble rock wool developed a
      leached surface with porous honeycomb structure. SEM analysis showed the
      dissolution for glass wool is mainly due to breakage transverse of fiber at pH
      7.4. AES dissolution constant (Kdis) was the highest at pH 7.4, while at pH 4.5
      only biosoluble rockwool 1 showed a higher Kdis. 

PMID- 24910420
TI  - Potential avoidability of planned cesarean sections in a French national
      database.
AB  - OBJECTIVE: To study the frequency and determinants of potentially avoidable
      planned cesarean sections, with a classification based on their indications,
      maternal obstetric history, and information about the current pregnancy. DESIGN:
      Cross-sectional population-based study. SETTING: All maternity units in France (n
      = 535). POPULATION: A total of 14,681 women from the 2010 French National
      Perinatal Survey, a routine survey of a representative sample of births. METHODS:
      Planned cesareans were classified in two groups: potentially avoidable and
      unavoidable. The classification was based on the French national guidelines and
      used data from medical records. We used logistic regression analyses to compare
      characteristics of the mothers with potentially avoidable cesareans with those of
      women who had a trial of labor. Analyses were performed separately in primiparas
      and multiparas. MAIN OUTCOME MEASURE: Rate of potentially avoidable planned
      cesarean sections. RESULTS: The overall planned cesarean rate was 10.9%; 28% of
      these cesareans were found to be potentially avoidable. Breech presentation and
      history of one previous cesarean accounted for 83% of them. Determinants of
      potential avoidability were maternal age >35 years, intensive surveillance during
      pregnancy, and private status of the unit [adjusted odds ratio (OR) 1.9, 95% CI
      1.2-3.2 among primiparas; adjusted OR 2.5, 95% CI 1.5-4.3 among multiparas].
      Obesity was also a significant determinant but only among multiparas (adjusted OR
      2.7, 95% CI 1.9-3.8). No association was found with maternal social
      characteristics. CONCLUSION: Our results suggest a high proportion of potentially
      avoidable cesareans and highlight the associated obstetric situations. They can
      help to target policies aimed at reducing cesarean rates.

PMID- 24910421
TI  - Primary and secondary care clinicians' views on self-treatment of COPD
      exacerbations: a multinational qualitative study.
AB  - OBJECTIVE: To explore clinicians' views on antibiotic and/or steroid 'rescue
      packs' used as self-treatment for patients with exacerbations of COPD. METHODS:
      21 focus groups conducted in 7 countries--Netherlands, Russia, Norway, China
      (Hong Kong), Wales, Germany and Poland involving 142 primary care clinicians and
      pulmonologists. RESULTS: We found wide variation in reported use of and attitudes
      to self-treatment among GPs and pulmonologists in the participating countries.
      Clinicians highlighted the importance of identifying patients who were most
      likely to benefit (those with more severe disease) and most likely to use the
      treatment appropriately (demonstrated by previous behaviour), and the importance
      of adequate patient education and ongoing communication in regard to use of self
      treatment packs. Clinicians recognised patient empowerment and facilitating
      prompt treatment as potential benefits of self-treatment. However, many felt they
      did not have the time or resources for appropriate patient selection and
      education. CONCLUSION: Clinicians do not feel it is appropriate to offer self
      treatment rescue packs to all patients routinely without careful consideration of
      patient understanding of their illness and their capacity for self-management.
      PRACTICE IMPLICATIONS: Adequate resources and continuity of patient care are
      required for clinicians to feel confident in the safe and effective
      implementation of this strategy.

PMID- 24910422
TI  - Building skill in heart failure self-care among community dwelling older adults:
      results of a pilot study.
AB  - OBJECTIVE: Most of the day-to-day care for heart failure (HF) is done by the
      patient at home and requires skill in self-care. In this randomized controlled
      trial (RCT) we tested the efficacy of a community-based skill-building
      intervention on HF self-care, knowledge and health-related quality of life (HRQL)
      at 1- and 3-months. METHODS: An ethnically diverse sample (n=75) of patients with
      HF (53% female; 32% Hispanic, 27% Black; mean age 69.9+/-10 years) was randomized
      to the intervention group (IG) or a wait-list control group (CG). The protocol
      intervention focused on tactical and situational HF self-care skill development
      delivered by lay health educators in community senior centers. Data were analyzed
      using mixed (between-within subjects) ANOVA. RESULTS: There was a significant
      improvement in self-care maintenance [F(2,47)=3.42, p=.04, (Cohen's f=.38)], self
      care management [F(2,41)=4.10, p=.02, (Cohen's f=.45) and HF knowledge
      [F(2,53)=8.00, p=.001 (Cohen's f=.54)] in the IG compared to the CG. CONCLUSIONS:
      The skill-building intervention improved self-care and knowledge but not HRQL in
      this community-dwelling sample. PRACTICE IMPLICATIONS: Delivering an intervention
      in a community setting using lay health educators provides an alternative to
      clinic- or home-based teaching that may be useful across diverse populations and
      geographically varied settings.

PMID- 24910423
TI  - Synchronous primary serous ovarian cancer and renal cell carcinoma.

PMID- 24910424
TI  - Individuals in the criminal justice system show differences in cooperative
      behaviour: Implications from cooperative games.
AB  - BACKGROUND: The high rate of incarceration in the USA warrants continued
      exploration into understanding and ameliorating criminal behaviour. The growing
      use of cooperative games to measure developing prosocial behaviours has never
      been explored in a US criminal justice population. AIMS: The aim of this study is
      to examine cooperative game play among offenders under supervision in the
      community. We hypothesised that the offenders would use more guarded and self
      preserving strategies and be more likely to excel in short-lived interactions
      than law-abiding community citizens. METHODS: Community supervised offenders (83)
      and general population comparison participants (41) were recruited by town centre
      adverts placed in popular shops. Using the supervision centres as venues, all
      participants were asked to complete four cooperative games (prisoner's dilemma,
      public goods game, ultimatum game and trust game), not knowing the identity of
      the other player who was always, in fact, the experimenter. RESULTS: The offender
      and general population groups were similar in age (early 30s), sex (2/3 men),
      race (45% white) and IQ distribution (low average range). Offenders made lower
      offers in the ultimatum game, had lower scores in the prisoner's dilemma, made
      lower investments and offered lower returns in the trust game and contributed
      less in the public goods game. CONCLUSIONS: Even community-based offenders thus
      seem to have deficits in the kinds of gameplay, which are informed by theories of
      social cooperation, but the direction of relationship with offending remains
      unclear. The apparent deficits may reflect adaptation to a hostile environment
      where trust and reciprocity are not rewarded. It is also important to recognise
      that these community-based offenders did develop play indicative of trust and
      reciprocity, they just did so more slowly than the comparison group. This may
      have implications for allowing time for rapport to develop in supervisory
      relationships. Finally, offenders may benefit from learning that although more
      guarded behaviours may be adaptive in a rough neighbourhood or in jail, they may
      be maladaptive and limit their success in other settings such as the work place.

PMID- 24910425
TI  - Participatory methods for the assessment of the ownership status of free-roaming
      dogs in Bali, Indonesia, for disease control and animal welfare.
AB  - The existence of unowned, free-roaming dogs capable of maintaining adequate body
      condition without direct human oversight has serious implications for disease
      control and animal welfare, including reducing effective vaccination coverage
      against rabies through limiting access for vaccination, and absolving humans from
      the responsibility of providing adequate care for a domesticated species. Mark
      recapture methods previously used to estimate the fraction of unowned dogs in
      free-roaming populations have limitations, particularly when most of the dogs are
      owned. We used participatory methods, described as Participatory Rural Appraisal
      (PRA), as a novel alternative to mark-recapture methods in two villages in Bali,
      Indonesia. PRA was implemented at the banjar (or sub-village)-level to obtain
      consensus on the food sources of the free-roaming dogs. Specific methods included
      semi-structured discussion, visualisation tools and ranking. The PRA results
      agreed with the preceding household surveys and direct observations, designed to
      evaluate the same variables, and confirmed that a population of unowned, free
      roaming dogs in sufficiently good condition to be sustained independently of
      direct human support was unlikely to exist. 

PMID- 24910426
TI  - Mitochondrial pyruvate carrier 2 hypomorphism in mice leads to defects in glucose
      stimulated insulin secretion.
AB  - Carrier-facilitated pyruvate transport across the inner mitochondrial membrane
      plays an essential role in anabolic and catabolic intermediary metabolism.
      Mitochondrial pyruvate carrier 2 (Mpc2) is believed to be a component of the
      complex that facilitates mitochondrial pyruvate import. Complete MPC2 deficiency
      resulted in embryonic lethality in mice. However, a second mouse line expressing
      an N-terminal truncated MPC2 protein (Mpc2(Delta16)) was viable but exhibited a
      reduced capacity for mitochondrial pyruvate oxidation. Metabolic studies
      demonstrated exaggerated blood lactate concentrations after pyruvate, glucose, or
      insulin challenge in Mpc2(Delta16) mice. Additionally, compared with wild-type
      controls, Mpc2(Delta16) mice exhibited normal insulin sensitivity but elevated
      blood glucose after bolus pyruvate or glucose injection. This was attributable to
      reduced glucose-stimulated insulin secretion and was corrected by sulfonylurea
      KATP channel inhibitor administration. Collectively, these data are consistent
      with a role for MPC2 in mitochondrial pyruvate import and suggest that Mpc2
      deficiency results in defective pancreatic beta cell glucose sensing. 

PMID- 24910427
TI  - Long-term health of dopaminergic neuron transplants in Parkinson's disease
      patients.
AB  - To determine the long-term health and function of transplanted dopamine neurons
      in Parkinson's disease (PD) patients, the expression of dopamine transporters
      (DATs) and mitochondrial morphology were examined in human fetal midbrain
      cellular transplants. DAT was robustly expressed in transplanted dopamine neuron
      terminals in the reinnervated host putamen and caudate for at least 14 years
      after transplantation. The transplanted dopamine neurons showed a healthy and
      nonatrophied morphology at all time points. Labeling of the mitochondrial outer
      membrane protein Tom20 and alpha-synuclein showed a typical cellular pathology in
      the patients' own substantia nigra, which was not observed in transplanted
      dopamine neurons. These results show that the vast majority of transplanted
      neurons remain healthy for the long term in PD patients, consistent with clinical
      findings that fetal dopamine neuron transplants maintain function for up to 15-18
      years in patients. These findings are critically important for the rational
      development of stem-cell-based dopamine neuronal replacement therapies for PD. 

PMID- 24910428
TI  - Modularized functions of the Fanconi anemia core complex.
AB  - The Fanconi anemia (FA) core complex provides the essential E3 ligase function
      for spatially defined FANCD2 ubiquitination and FA pathway activation. Of the
      seven FA gene products forming the core complex, FANCL possesses a RING domain
      with demonstrated E3 ligase activity. The other six components do not have
      clearly defined roles. Through epistasis analyses, we identify three functional
      modules in the FA core complex: a catalytic module consisting of FANCL, FANCB,
      and FAAP100 is absolutely required for the E3 ligase function, and the FANCA
      FANCG-FAAP20 and the FANCC-FANCE-FANCF modules provide nonredundant and ancillary
      functions that help the catalytic module bind chromatin or sites of DNA damage.
      Disruption of the catalytic module causes complete loss of the core complex
      function, whereas loss of any ancillary module component does not. Our work
      reveals the roles of several FA gene products with previously undefined functions
      and a modularized assembly of the FA core complex.

PMID- 24910429
TI  - Acquired dependence of acute myeloid leukemia on the DEAD-box RNA helicase DDX5.
AB  - Acute myeloid leukemia (AML) therapy involves compounds that are cytotoxic to
      both normal and cancer cells, and relapsed AML is resistant to subsequent
      chemotherapy. Thus, agents are needed that selectively kill AML cells with
      minimal toxicity. Here, we report that AML is dependent on DDX5 and that
      inhibiting DDX5 expression slows AML cell proliferation in vitro and AML
      progression in vivo but is not toxic to cells from normal bone marrow. Inhibition
      of DDX5 expression in AML cells induces apoptosis via induction of reactive
      oxygen species (ROS). This apoptotic response can be blocked either by BCL2
      overexpression or treatment with the ROS scavenger N-acetyl-L-cysteine. Combining
      DDX5 knockdown with a BCL2 family inhibitor cooperates to induce cell death in
      AML cells. By inhibiting DDX5 expression in vivo, we show that DDX5 is
      dispensable for normal hematopoiesis and tissue homeostasis. These results
      validate DDX5 as a potential target for blocking AML.

PMID- 24910430
TI  - Downmodulation of CCR7 by HIV-1 Vpu results in impaired migration and chemotactic
      signaling within CD4+ T cells.
AB  - The chemokine receptor CCR7 plays a crucial role in the homing of central memory
      and naive T cells to peripheral lymphoid organs. Here, we show that the HIV-1
      accessory protein Vpu downregulates CCR7 on the surface of CD4(+) T cells. Vpu
      and CCR7 were found to specifically interact and colocalize within the trans
      Golgi network, where CCR7 is retained. Downmodulation of CCR7 did not involve
      degradation or endocytosis and was strictly dependent on Vpu expression.
      Stimulation of HIV-1-infected primary CD4(+) T cells with the CCR7 ligand CCL19
      resulted in reduced mobilization of Ca(2+), reduced phosphorylation of Erk1/2,
      and impaired migration toward CCL19. Specific amino acid residues within the
      transmembrane domain of Vpu that were previously shown to be critical for BST-2
      downmodulation (A14, A18, and W22) were also necessary for CCR7 downregulation.
      These results suggest that BST-2 and CCR7 may be downregulated via similar
      mechanisms.

PMID- 24910431
TI  - Negative feedback in genetic circuits confers evolutionary resilience and
      capacitance.
AB  - Natural selection for specific functions places limits upon the amino acid
      substitutions a protein can accept. Mechanisms that expand the range of tolerable
      amino acid substitutions include chaperones that can rescue destabilized proteins
      and additional stability-enhancing substitutions. Here, we present an alternative
      mechanism that is simple and uses a frequently encountered network motif.
      Computational and experimental evidence shows that the self-correcting, negative
      feedback gene regulation motif increases repressor expression in response to
      deleterious mutations and thereby precisely restores repression of a target gene.
      Furthermore, this ability to rescue repressor function is observable across the
      Eubacteria kingdom through the greater accumulation of amino acid substitutions
      in negative-feedback transcription factors compared to genes they control. We
      propose that negative feedback represents a self-contained genetic canalization
      mechanism that preserves phenotype while permitting access to a wider range of
      functional genotypes. 

PMID- 24910432
TI  - Age-related dysfunction in mechanotransduction impairs differentiation of human
      mammary epithelial progenitors.
AB  - Dysfunctional progenitor and luminal cells with acquired basal cell properties
      accumulate during human mammary epithelial aging for reasons not understood.
      Multipotent progenitors from women aged <30 years were exposed to a
      physiologically relevant range of matrix elastic modulus (stiffness). Increased
      stiffness causes a differentiation bias towards myoepithelial cells while
      reducing production of luminal cells and progenitor maintenance. Lineage
      representation in progenitors from women >55 years is unaffected by physiological
      stiffness changes. Efficient activation of Hippo pathway transducers YAP and TAZ
      is required for the modulus-dependent myoepithelial/basal bias in younger
      progenitors. In older progenitors, YAP and TAZ are activated only when stressed
      with extraphysiologically stiff matrices, which bias differentiation towards
      luminal-like phenotypes. In vivo YAP is primarily active in myoepithelia of
      younger breasts, but localization and activity increases in luminal cells with
      age. Thus, aging phenotypes of mammary epithelia may arise partly because
      alterations in Hippo pathway activation impair microenvironment-directed
      differentiation and lineage specificity.

PMID- 24910433
TI  - The ROS/SUMO axis contributes to the response of acute myeloid leukemia cells to
      chemotherapeutic drugs.
AB  - Chemotherapeutic drugs used in the treatment of acute myeloid leukemias (AMLs)
      are thought to induce cancer cell death through the generation of DNA double
      strand breaks. Here, we report that one of their early effects is the loss of
      conjugation of the ubiquitin-like protein SUMO from its targets via reactive
      oxygen species (ROS)-dependent inhibition of the SUMO-conjugating enzymes.
      Desumoylation regulates the expression of specific genes, such as the
      proapoptotic gene DDIT3, and helps induce apoptosis in chemosensitive AMLs. In
      contrast, chemotherapeutics do not activate the ROS/SUMO axis in chemoresistant
      cells. However, pro-oxidants or inhibition of the SUMO pathway by anacardic acid
      restores DDIT3 expression and apoptosis in chemoresistant cell lines and patient
      samples, including leukemic stem cells. Finally, inhibition of the SUMO pathway
      decreases tumor growth in mice xenografted with AML cells. Thus, targeting the
      ROS/SUMO axis might constitute a therapeutic strategy for AML patients resistant
      to conventional chemotherapies.

PMID- 24910434
TI  - APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to
      human papillomavirus-driven tumor development.
AB  - APOBEC3B cytosine deaminase activity has recently emerged as a significant
      mutagenic factor in human cancer. APOBEC activity is induced in virally infected
      cells, and APOBEC signature mutations occur at high frequency in cervical cancers
      (CESC), over 99% of which are caused by human papillomavirus (HPV). We tested
      whether APOBEC-mediated mutagenesis is particularly important in HPV-associated
      tumors by comparing the exomes of HPV+ and HPV- head and neck squamous cell
      carcinomas (HNSCCs) sequenced by The Cancer Genome Atlas project. As expected,
      HPV- HNSCC displays a smoking-associated mutational signature, whereas our data
      suggest that reduced exposure to exogenous carcinogens in HPV+ HNSCC creates a
      selective pressure that favors emergence of tumors with APOBEC-mediated driver
      mutations. Finally, we provide evidence that APOBEC activity is responsible for
      the generation of helical domain hot spot mutations in the PIK3CA gene across
      multiple cancers. Our findings implicate APOBEC activity as a key driver of
      PIK3CA mutagenesis and HPV-induced transformation.

PMID- 24910435
TI  - Kainate receptors coexist in a functional complex with KCC2 and regulate chloride
      homeostasis in hippocampal neurons.
AB  - KCC2 is the neuron-specific K+-Cl(-) cotransporter required for maintaining low
      intracellular Cl(-), which is essential for fast inhibitory synaptic transmission
      in the mature CNS. Despite the requirement of KCC2 for inhibitory synaptic
      transmission, understanding of the cellular mechanisms that regulate KCC2
      expression and function is rudimentary. We examined KCC2 in its native protein
      complex in vivo to identify key KCC2-interacting partners that regulate KCC2
      function. Using blue native-polyacrylamide gel electrophoresis (BN-PAGE), we
      determined that native KCC2 exists in a macromolecular complex with kainate-type
      glutamate receptors (KARs). We found that KAR subunits are required for KCC2
      oligomerization and surface expression. In accordance with this finding, acute
      and chronic genetic deletion of KARs decreased KCC2 function and weakened
      synaptic inhibition in hippocampal neurons. Our results reveal KARs as regulators
      of KCC2, significantly advancing our growing understanding of the tight interplay
      between excitation and inhibition.

PMID- 24910436
TI  - MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by
      haplotype differences and developmental stage.
AB  - The dynamics by which mitochondrial DNA (mtDNA) evolves within organisms are
      still poorly understood, despite the fact that inheritance and proliferation of
      mutated mtDNA cause fatal and incurable diseases. When two mtDNA haplotypes are
      present in a cell, it is usually assumed that segregation (the proliferation of
      one haplotype over another) is negligible. We challenge this assumption by
      showing that segregation depends on the genetic distance between haplotypes. We
      provide evidence by creating four mouse models containing mtDNA haplotype pairs
      of varying diversity. We find tissue-specific segregation in all models over a
      wide range of tissues. Key findings are segregation in postmitotic tissues
      (important for disease models) and segregation covering all developmental stages
      from prenatal to old age. We identify four dynamic regimes of mtDNA segregation.
      Our findings suggest potential complications for therapies in human populations:
      we propose "haplotype matching" as an approach to avoid these issues. 

PMID- 24910437
TI  - Distinct stromal cell factor combinations can separately control hematopoietic
      stem cell survival, proliferation, and self-renewal.
AB  - Hematopoietic stem cells (HSCs) are identified by their ability to sustain
      prolonged blood cell production in vivo, although recent evidence suggests that
      durable self-renewal (DSR) is shared by HSC subtypes with distinct self
      perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo,
      but molecularly defined conditions that support similar responses in vitro are
      lacking. We hypothesized that this might require a combination of factors that
      differentially promote HSC viability, proliferation, and self-renewal. We now
      demonstrate that HSC survival and maintenance of DSR potential are variably
      supported by different Steel factor (SF)-containing cocktails with similar HSC
      mitogenic activities. In addition, stromal cells produce other factors, including
      nerve growth factor and collagen 1, that can antagonize the apoptosis of
      initially quiescent adult HSCs and, in combination with SF and interleukin-11,
      produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings
      point to the molecular basis of HSC control and expansion.

PMID- 24910438
TI  - The DGCR8 RNA-binding heme domain recognizes primary microRNAs by clamping the
      hairpin.
AB  - Canonical primary microRNA transcripts (pri-miRNAs) are characterized by a ~30 bp
      hairpin flanked by single-stranded regions. These pri-miRNAs are recognized and
      cleaved by the Microprocessor complex consisting of the Drosha nuclease and its
      obligate RNA-binding partner DGCR8. It is not well understood how the
      Microprocessor specifically recognizes pri-miRNA substrates. Here, we show that
      in addition to the well-known double-stranded RNA-binding domains, DGCR8 uses a
      dimeric heme-binding domain to directly contact pri-miRNAs. This RNA-binding heme
      domain (Rhed) directs two DGCR8 dimers to bind each pri-miRNA hairpin. The two
      Rhed-binding sites are located at both ends of the hairpin. The Rhed and its RNA
      binding surface are important for pri-miRNA processing activity. Additionally,
      the heme cofactor is required for formation of processing-competent DGCR8-pri
      miRNA complexes. Our study reveals a unique protein-RNA interaction central to
      pri-miRNA recognition. We propose a unifying model in which two DGCR8 dimers
      clamp a pri-miRNA hairpin using their Rheds.

PMID- 24910439
TI  - RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and
      splicing programs in cell differentiation.
AB  - The RNA helicases DDX5 and DDX17 are members of a large family of highly
      conserved proteins that are involved in gene-expression regulation; however,
      their in vivo targets and activities in biological processes such as cell
      differentiation, which requires reprogramming of gene-expression programs at
      multiple levels, are not well characterized. Here, we uncovered a mechanism by
      which DDX5 and DDX17 cooperate with heterogeneous nuclear ribonucleoprotein
      (hnRNP) H/F splicing factors to define epithelial- and myoblast-specific splicing
      subprograms. We then observed that downregulation of DDX5 and DDX17 protein
      expression during myogenesis and epithelial-to-mesenchymal transdifferentiation
      contributes to the switching of splicing programs during these processes.
      Remarkably, this downregulation is mediated by the production of miRNAs induced
      upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also
      function as coregulators of master transcriptional regulators of differentiation,
      we propose to name these proteins "master orchestrators" of differentiation that
      dynamically orchestrate several layers of gene expression.

PMID- 24910440
TI  - SUMOylation of Psmd1 controls Adrm1 interaction with the proteasome.
AB  - SUMOylation is the covalent conjugation of SUMO polypeptides to cellular target
      proteins. Psmd1 is a subunit of the proteasomal 19S regulatory particle that acts
      as a docking site for Adrm1, another proteasome subunit that recruits
      ubiquitinated substrates for proteolysis. Here, we show that the SUMO
      deconjugating enzyme xSENP1 specifically interacts with Psmd1 and that disruption
      of xSENP1 targeting delays mitotic exit. Psmd1 becomes SUMOylated through the
      action of the SUMO E3 enzyme PIASy. We mapped SUMOylation sites within Psmd1 and
      found that SUMOylation of a critical lysine immediately adjacent to the Adrm1
      binding domain regulates the association of Adrm1 with Psmd1. Together, our
      findings suggest that the interaction of Psmd1 with Adrm1 is controlled by
      SUMOylation in a manner that may alter proteasome composition and function. These
      findings demonstrate a mechanism for regulation of ubiquitin-mediated protein
      degradation by ubiquitin-like proteins of the SUMO family.

PMID- 24910442
TI  - Combination effect of ultrasound and shake as a mechanical action for textile
      cleaning.
AB  - The ultrasonic cleaning of artificially soiled fabrics with and without shake was
      carried out in an aqueous anionic surfactant solution. The polyester, cotton and
      polyester/cotton (65/35) fabrics were soiled with oleic acid or carbon black as a
      model soil, and cleaned together with their original fabrics with applying
      ultrasound for 5min. The detergency and the soil redeposition were determined
      from the change in the Kubelka-Munk function of the soiled and original fabric
      surfaces due to the cleaning. For any fabric, the removal of oleic acid and
      carbon black from the soiled fabric and their redeposition onto the original
      fabric increased with increasing electric power consumption of ultrasound. When
      ultrasound and shake were applied at the same time, the detergency further
      increased for any electric power consumption. The maximum detergency obtained
      with combination of ultrasound 340W and shake 160spm was compared with detergency
      obtained with Wascator, a horizontal axis drum type washer. It was found that the
      ultrasound/shake combination cleaning enabled efficient removal of both soils
      from any fabric and the detergency of the polyester fabrics was comparable to
      that with Wascator. The mechanical action during the washing was evaluated by two
      mechanical action test pieces commercially available, which indicated that the
      ultrasound/shake combination cleaning provided gentle mechanical action to the
      fabric in comparison with the drum type washer. The SEM observations showed the
      damage of the fabric and fiber surfaces was negligibly small after the
      ultrasound/shake combination washing. 

PMID- 24910441
TI  - Identification, characterization and analysis of expression of gene encoding
      carboxypeptidase A in Anopheles culicifacies A (Diptera: culicidae).
AB  - Carboxypeptidases are the digestive enzymes which cleave single amino acid
      residue from c-terminus of the protein. Digestive carboxypeptidase A gene
      regulatory elements in insects have shown their efficiency to drive midgut
      specific expression in transgenic mosquitoes. However no endogenous promoter has
      been reported for Indian malaria vector Anopheles culicifacies which is major
      vector in Indian subcontinent. Here we report cloning of carboxypeptidase A gene
      in the An. culicifacies A including its 5' upstream regions and named AcCP. In
      the upstream region of the gene an arthropod initiator sequence and two repeat
      sequences of the particular importance TTATC and GTTTT were also identified. The
      1290 base pairs open reading frame encodes a protein of 48.5kDa. The coding
      region of the gene shares 82% and 72% similarity at nucleotide level with
      Anopheles gambiae and Ae. aegypti carboxypeptidase A gene, respectively. The peak
      expression of the gene was found to be at 3h after blood feeding and this is
      limited to midgut only. Based on the protein sequence, 3D structure of the AcCP
      was predicted and the active centre of the enzyme was predicted to consist of GLN
      183, GLU 186, HIS 308 and Ser 309 amino acid residues. Comparison of the protein
      sequence among different genera revealed the conservation of zinc binding
      residues. Phylogenetically, AcCP was found most closely related to An. gambiae. 

PMID- 24910443
TI  - Comparison between several methods of total lipid extraction from Chlorella
      vulgaris biomass.
AB  - The use of lipids obtained from microalgae biomass has been described as a
      promising alternative for production of biodiesel to replace petro-diesel. It
      involves steps such as the cultivation of microalgae, biomass harvesting,
      extraction and transesterification of lipids. The purpose of the present study
      was to compare different methods of extracting total lipids. These methods were
      tested in biomass of Chlorella vulgaris with the solvents ethanol, hexane and a
      mixture of chloroform:methanol in ratios 1:2 and 2:1. The solvents were
      associated with other mechanisms of cell disruption such as use of a Potter
      homogenizer and ultrasound treatment. The percentage of triglycerides in the
      total lipids was determinated by the glycerol-3-phosphate oxidase-p-chlorophenol
      method (triglycerides monoreagent K117; Bioclin). Among the tested methods, the
      mixture of chloroform:methanol (2:1) assisted by ultrasound was most efficient,
      extracting an average of 19% of total lipids, of which 55% were triglycerides.
      The gas chromatographic analysis did not show differences in methyl ester
      profiles of oils extracted under the different methods. 

PMID- 24910445
TI  - Similar and contrasting dimensions of social cognition in schizophrenia and
      healthy subjects.
AB  - Schizophrenia patients experience substantial impairments in social cognition
      (SC) and these deficits are associated with their poor functional outcome. Though
      SC is consistently shown to emerge as a cognitive dimension distinct from
      neurocognition, the dimensionality of SC is poorly understood. Moreover,
      comparing the components of SC between schizophrenia patients and healthy
      comparison subjects would provide specific insights on the construct validity of
      SC. We conducted principal component analyses of eight SC test scores
      (representing four domains of SC, namely, theory of mind, emotion processing,
      social perception and attributional bias) independently in 170 remitted
      schizophrenia patients and 111 matched healthy comparison subjects. We also
      conducted regression analyses to evaluate the relative contribution of individual
      SC components to other symptom dimensions, which are important clinical
      determinants of functional outcome (i.e., neurocognition, negative symptoms,
      motivational deficits and insight) in schizophrenia. A three-factor solution
      representing socio-emotional processing, social-inferential ability and external
      attribution components emerged in the patient group that accounted for 64.43% of
      the variance. In contrast, a two-factor solution representing socio-emotional
      processing and social-inferential ability was derived in the healthy comparison
      group that explained 56.5% of the variance. In the patient group, the social
      inferential component predicted negative symptoms and motivational deficits. Our
      results suggest the presence of a multidimensional SC construct. The
      dimensionality of SC observed across the two groups, though not identical,
      displayed important parallels. Individual components also demonstrated distinct
      patterns of association with other symptom dimensions, thus supporting their
      external validity. 

PMID- 24910444
TI  - Extracellular matrix elasticity and topography: material-based cues that affect
      cell function via conserved mechanisms.
AB  - Chemical, mechanical, and topographic extracellular matrix (ECM) cues have been
      extensively studied for their influence on cell behavior. These ECM cues alter
      cell adhesion, cell shape, and cell migration and activate signal transduction
      pathways to influence gene expression, proliferation, and differentiation. ECM
      elasticity and topography, in particular, have emerged as material properties of
      intense focus based on strong evidence these physical cues can partially dictate
      stem cell differentiation. Cells generate forces to pull on their adhesive
      contacts, and these tractional forces appear to be a common element of cells'
      responses to both elasticity and topography. This review focuses on recently
      published work that links ECM topography and mechanics and their influence on
      differentiation and other cell behaviors. We also highlight signaling pathways
      typically implicated in mechanotransduction that are (or may be) shared by cells
      subjected to topographic cues. Finally, we conclude with a brief discussion of
      the potential implications of these commonalities for cell based therapies and
      biomaterial design.

PMID- 24910446
TI  - Impairment in emotional modulation of attention and memory in schizophrenia.
AB  - Emotion plays a critical role in cognition and goal-directed behavior via complex
      interconnections between the emotional and motivational systems. It has been
      hypothesized that the impairment in goal-directed behavior widely noted in
      schizophrenia may result from defects in the interaction between the neural
      (ventral) emotional system and (rostral) cortical processes. The present study
      examined the impact of emotion on attention and memory in schizophrenia. Twenty
      five individuals with schizophrenia related psychosis and 25 healthy control
      subjects were administered a computerized task in which they were asked to search
      for target images during a Rapid Serial Visual Presentation of pictures. Target
      stimuli were either positive or negative, or neutral images presented at either
      200ms or 700ms lag. Additionally, a visual hedonic task was used to assess
      differences between the schizophrenia group and controls on ratings of valence
      and arousal from the picture stimuli. Compared to controls, individuals with
      schizophrenia detected fewer emotional images under both the 200ms and 700ms lag
      conditions. Multivariate analyses showed that the schizophrenia group also
      detected fewer positive images under the 700ms lag condition and fewer negative
      images under the 200ms lag condition. Individuals with schizophrenia reported
      higher pleasantness and unpleasantness ratings than controls in response to
      neutral stimuli, while controls reported higher arousal ratings for neutral and
      positive stimuli compared to the schizophrenia group. These results highlight
      dysfunction in the neural modulation of emotion, attention, and cortical
      processing in schizophrenia, adding to the growing but mixed body of literature
      on emotion processing in the disorder. 

PMID- 24910448
TI  - BDCA3(+)CLEC9A(+) human dendritic cell function and development.
AB  - Dendritic cells (DC) are the most potent antigen presenting cells (APC). They
      comprise a family of different subsets and play an essential role in the
      induction and regulation of immune responses. Recently, gene expression profiling
      identified BDCA3(+)CLEC9A(+) DC as a separate human DC subset. This subset was
      identified in blood, where they represent the smallest population of human DC, as
      well as in lymphoid and peripheral tissues. This review summarizes the
      phenotypic, functional and developmental characteristics of BDCA3(+)CLEC9A(+) DC
      in relation to their mouse equivalents CD8alpha(+) DC and CD103(+) DC and other
      human DC subsets. Apart from being potent antigen presenting cells, their
      specialized functional capacities compared to other human DC subsets, indicate
      that these BDCA3(+)CLEC9A(+) DC are of major importance in the induction of anti
      viral and anti-tumor immunity. Further characterization of their functional
      properties, developmental pathways and underlying molecular mechanisms may
      identify target molecules to fully exploit the immune modulatory function of
      BDCA3(+)CLEC9A(+) DC and potential use of these cells in immunotherapy. 

PMID- 24910449
TI  - Roles of TGF-beta family signals in the fate determination of pluripotent stem
      cells.
AB  - Members of the transforming growth factor-beta (TGF-beta) family have been
      implicated in embryogenesis as well as in the determination of the cell fates of
      mouse and human embryonic stem (ES) cells, which are characterized by their self
      renewal and pluripotency. The cellular responses to TGF-beta family signals are
      divergent depending on the cellular context and local environment. TGF-beta
      family signals play critical roles both in the maintenance of the pluripotent
      state of ES cells by inducing the expression of Nanog, Oct4, and Sox2, and in
      their differentiation into various cell types by regulating the expression of
      master regulatory genes. Moreover, multiple lines of evidence have suggested the
      importance of TGF-beta family signals in establishing induced pluripotent stem
      (iPS) cells. Since ES and iPS cells have great potential for applications in
      regenerative medicine, it is critical to figure out the mechanisms underlying
      their self-renewal, pluripotency, and differentiation. Here, we discuss the roles
      of TGF-beta family ligands and their downstream signaling molecules, Smad
      proteins, in the maintenance of the pluripotency and lineage specification of
      mouse and human ES and iPS cells. 

PMID- 24910447
TI  - Determinants and implications of mRNA poly(A) tail size--does this protein make
      my tail look big?
AB  - While the phenomenon of polyadenylation has been well-studied, the dynamics of
      poly(A) tail size and its impact on transcript function and cell biology are less
      well-appreciated. The goal of this review is to encourage readers to view the
      poly(A) tail as a dynamic, changeable aspect of a transcript rather than a simple
      static entity that marks the 3' end of an mRNA. This could open up new angles of
      regulation in the post-transcriptional control of gene expression throughout
      development, differentiation and cancer. 

PMID- 24910450
TI  - Tissue remodeling in periplaque regions of multiple sclerosis spinal cord
      lesions.
AB  - Our knowledge of multiple sclerosis (MS) neuropathology has benefited from a
      number of studies that provided an in-depth description of plaques and, more
      recently, diffuse alterations of the normal-appearing white or grey matter.
      However, there have been few studies focusing on the periplaque regions
      surrounding demyelinated plaques, notably in MS spinal cords. In this context,
      the present study aimed to analyze the molecular immunopathology of periplaque
      demyelinated lesions (PDLs) in the spinal cord of patients with a progressive
      form of MS. To achieve this goal, the neuropathological features of PDLs were
      analyzed in postmortem tissues derived from the cervical spinal cord of 21
      patients with primary or secondary progressive MS. We found that PDLs covered
      unexpectedly large areas of incomplete demyelination and were characterized by
      the superimposition of pro- and anti-inflammatory molecular signatures.
      Accordingly, macrophages/microglia accumulated in PDLs but exhibited a poor
      phagocytic activity toward myelin debris. Interestingly, while genes of the
      oligodendrocyte lineage were consistently down-regulated in PDLs, astrocyte
      related molecules such as aquaporin 4, connexin 43 and the glutamate transporter
      EAAT1, were significantly upregulated in PDLs at the mRNA and protein levels.
      Overall, our work indicates that in the spinal cord of patients with a
      progressive form of MS, a tissue remodeling process that is temporally remote
      from plaque development takes place in PDLs. We propose that in spinal cord PDLs,
      this process is supported by subtle alterations of astrocyte functions and by low
      grade inflammatory events that drive a slowly progressive loss of myelin and a
      failure of remyelination.

PMID- 24910451
TI  - Secondary cytoreductive surgery in patients with isolated platinum-resistant
      recurrent ovarian cancer: a retrospective analysis.
AB  - OBJECTIVE: To analyze the impact of secondary cytoreductive surgery (SCS) on
      survival outcome in a retrospective series of isolated platinum-resistant
      recurrent ovarian cancer. METHODS: We evaluate a consecutive series of 268
      ovarian cancer patients with platinum-resistant relapse. Isolated recurrence was
      defined as the presence of a single nodule, in a single anatomic site, and was
      observed in 27 cases (10.1%). In all women the presence of isolated relapse was
      assessed at radiological evaluation, and surgically confirmed in the SCS group.
      RESULTS: Among the 27 patients with isolated recurrence, 16 (59.3%) received
      chemotherapy alone, and 11 (40.7%) complete SCS followed by non-platinum based
      chemotherapy. No significant differences were observed in the distribution of
      baseline clinico-pathological characteristics, pattern of recurrent disease,
      duration of PFI, and type of salvage chemotherapy between the two groups. In the
      SCS group, 6 patients (54.5%) showed isolated peritoneal relapse and 5 women
      (45.4%) showed isolated lymph nodal recurrence, and were treated with
      peritonectomy and lymphadenectomy, according with site of relapse. Two post
      operative complications (18.2%) occurred: asymptomatic lymphocele and groin wound
      dehiscence. SCS significantly prolonged median time to first progression (12
      months vs 3 months; p-value=0.016), median time to second progression (8 months
      vs 3 months; p-value=0.037), and post-relapse survival (PRS) (32 months vs 8
      months; p-value=0.002). Residual tumor at 1st surgery (X(2)=5.690; p
      value=0.017), duration of PFI (X(2)=5.401; p-value=0.020), and complete SCS
      (X(2)=4.250; p-value=0.039) retains independent prognostic role for PRS in
      multivariate analysis. CONCLUSIONS: SCS prolongs PRS compared to chemotherapy
      alone in isolated platinum-resistant recurrent ovarian cancer.

PMID- 24910452
TI  - A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of
      platinum-sensitive recurrent ovarian cancer.
AB  - PURPOSE: The doublet gemcitabine and carboplatin is effective for the treatment
      of recurrent ovarian cancer, while multi-agent chemotherapy with bevacizumab may
      add additional benefit. This phase II study tested the efficacy and safety of a
      biweekly gemcitabine, carboplatin, and bevacizumab combination in patients with
      platinum-sensitive recurrent ovarian, peritoneal, or tubal cancer (ROC). PATIENTS
      AND METHODS: Eligible patients received concurrent gemcitabine 1000 mg/m(2),
      carboplatin area under the curve 3, and bevacizumab 10 mg/kg administered
      intravenously on days 1 and 15 every 28 days for six cycles or up to 24 cycles if
      clinical benefit occurred. The primary end points were progression-free survival
      (PFS) by RECIST, and safety; the secondary end points were objective response
      rates and overall survival. RESULTS: Overall, 45 patients were enrolled. The
      median PFS was 13.3 months (95% CI, 11.3 to 15.3). The objective response rate
      was 69%. Grade 4 hematologic toxicities included neutropenia (27%) and
      thrombocytopenia (2%). Grades 3 and 4 non-hematologic toxicities included fatigue
      (18%), pain (9%), and nausea/vomiting (4%). There were 2 episodes of
      cerebrovascular accidents, 2 noted DVTs, and no episodes of bowel perforation.
      Median OS was 36.1 months (95% CI, 26.7 to 45.5). CONCLUSION: Biweekly
      gemcitabine, carboplatin, and bevacizumab were an effective regimen in recurrent
      ovarian cancer, with comparable toxicity to recently reported day 1 gemcitabine,
      carboplatin, bevacizumab, and day 8 gemcitabine. Response rate and PFS are
      improved from reported outcomes of the gemcitabine carboplatin doublet. The
      degree to which biweekly dosing may present a more rationale schedule for this
      triplet should be evaluated further.

PMID- 24910453
TI  - Preoperative genetic testing affects surgical decision making in breast cancer
      patients.
AB  - OBJECTIVES: Our aim was to determine if BRCA mutation status changes surgical
      decision making in women who undergo genetic testing after the diagnosis of
      breast cancer. METHODS: This is a retrospective cohort study of breast cancer
      patients who had BRCA mutation testing performed prior to surgery. We compared
      surgical choice and change in surgical choice in women who tested positive for a
      BRCA mutation with those who tested negative. Surgery was considered the most
      definitive surgery within a year of diagnosis. Other data collected included age,
      race, stage, histology, receptor status, adjuvant treatment, gravity, parity, and
      family history. Variables were compared by BRCA status using Fisher's exact test
      and logistic regression. RESULTS: Three hundred and two women were included.
      Thirty-two (10.6%) were identified as carrying a BRCA mutation. Most women had
      early stage disease (55.6% T1 lesions, 72.8% node negative); 55.6% had breast
      conserving surgery, and the remaining had unilateral or bilateral mastectomy.
      BRCA mutation carriers were more likely to have both a personal history of breast
      cancer (RR 2.74, 95% CI=1.08-6.98) and hormone receptor-negative tumors (56.0%
      vs. 26.2%, p=0.002). BRCA mutation carriers were more likely to choose bilateral
      mastectomy with reconstruction (56.3% vs. 15.9%, p<0.0001); 71.9% of BRCA
      mutation carriers opted for a different surgery than what was initially planned
      by their surgeon as compared to 29% of mutation-negative patients (p<0.0001).
      CONCLUSIONS: BRCA mutation testing strongly influences surgical decision making
      in newly diagnosed breast cancer patients. For women who meet NCCN referral
      guidelines, genetic evaluation should be performed prior to surgical
      intervention.

PMID- 24910454
TI  - CD44(+) CD324(-) expression and prognosis in gastric cancer patients.
AB  - PURPOSE: To evaluate the frequency of cancer stem cell marker CD44 combined CD324
      expression in gastric cancer specimens and association of the expression with
      survival of gastric cancer patients. METHODS: A total of 203 patients with
      primary gastric cancer who underwent curative gastric resection with
      lymphadenectomy were studied. The expression of CD44 and CD324 was analyzed by
      immunohistochemistry and the association of CD44 and CD324 expression analyzed by
      clinicopathological characteristics. Survival of the patients was evaluated.
      RESULTS: CD44(+) CD324(-) tumors showed strong correlation with positive lymph
      node metastasis. Patients with CD44(-) CD324(+) had a significantly better
      prognosis (54.8%) than that with CD44(+) CD324(-) (24.5%). A multivariate Cox
      proportional hazards model using those variables associated with survival in our
      study (depth of invasion, tumor size, lymph node metastasis, gastrectomy, CD44
      expression, CD324 expression, CD44 and CD324 expression) revealed that CD44(+)
      CD324(-) expression (P = 0.005) was one of significant independent prognostic
      indicator, whereas CD44 expression (P = 0.081), CD324 expression (P = 0.068) was
      not. CONCLUSION: CD44(+) CD324(-) expression was one of significant independent
      prognostic survival factors for patients with gastric cancer.

PMID- 24910455
TI  - Graphene-sensitized microporous membrane/solvent microextraction for the
      preconcentration of cinnamic acid derivatives in Rhizoma Typhonii.
AB  - A novel graphene-sensitized microporous membrane/solvent microextraction method
      named microporous membrane/graphene/solvent synergistic microextraction, coupled
      with high-performance liquid chromatography and UV detection, was developed and
      introduced for the extraction and determination of three cinnamic acid
      derivatives in Rhizoma Typhonii. Several factors affecting performance were
      investigated and optimized, including the types of graphene and extraction
      solvent, concentration of graphene dispersed in octanol, sample phase pH, ionic
      strength, stirring rate, extraction time, extraction temperature, and sample
      volume. Under optimized conditions, the enrichment factors of cinnamic acid
      derivatives ranged from 75 to 269. Good linearities were obtained from 0.01 to 10
      MUg/mL for all analytes with regression coefficients between 0.9927 and 0.9994.
      The limits of quantification were <1 ng/mL, and satisfactory recoveries (99-104%)
      and precision (1.1-10.8%) were also achieved. The synergistic microextraction
      mechanism based on graphene sensitization was analyzed and described. The
      experimental results showed that the method was simple, sensitive, practical, and
      effective for the preconcentration and determination of cinnamic acid derivatives
      in Rhizoma Typhonii. 

PMID- 24910456
TI  - Electrocatalytic oxidation of cellulose at a gold electrode.
AB  - The electrochemical properties of cellulose dissolved in NaOH solution at a Au
      surface were investigated by cyclic voltammetry, FTIR spectroscopy, the
      electrochemical quartz crystal microbalance technique, and electrochemical
      impedance spectroscopy. The reaction products were characterized by SEM, TEM, and
      FTIR and NMR spectroscopy. The results imply that cellulose is irreversibly
      oxidized. Adsorption and desorption of hydroxide ions at the Au surface during
      potential cycling have an important catalytic role in the reaction (e.g.,
      approach of cellulose to the electrode surface, electron transfer,
      adsorption/desorption of the reaction species at the electrode surface).
      Moreover, two types of cellulose derivatives were obtained as products. One is a
      water-soluble cellulose derivative in which some hydroxyl groups are oxidized to
      carboxylic groups. The other derivative is a water-insoluble hybrid material
      composed of cellulose and Au nanoparticles (~4 nm). Furthermore, a reaction
      scheme of the electrocatalytic oxidation of cellulose at a gold electrode in a
      basic medium is proposed.

PMID- 24910458
TI  - Pulmonary artery stents in the recent era: Immediate and intermediate follow-up.
AB  - BACKGROUND: Long-term follow-up after stent dilation of native and acquired
      pulmonary artery stenosis is scarce in the pediatric population. Most cohorts
      include a myriad of anatomies and associated conditions. METHOD: In order to
      establish objective performance criteria, we performed a retrospective review of
      all patients who underwent unilateral pulmonary artery stenting in biventricular
      physiology at three centers from June 2006 to June 2011. RESULTS: Fifty-eight
      patients received 60 stents with Palmaz Genesis stent used most commonly (78%).
      Average age at implantation was 10.4 +/- 10.3 years and weight 31.6 +/- 21.8 kg.
      The immediate success rate was 98%, with improvement in minimal diameter from 5.1
      +/- 2 cm to 10.6 +/- 3 cm (P < 0.01). There were 10 complications (7 major and 3
      minor) and no acute mortality. One-year follow-up studies were available in 48
      patients (83%), including echocardiogram (60%), catheterization (28%), MRI (29%),
      and lung perfusion (31%). Follow-up echocardiogram showed mild increase in stent
      gradient, from 5.7 +/- 6.7 mm Hg post-procedure to 17.1 +/- 11.7 mm Hg. Follow-up
      catheterization showed no significant change in minimal stent diameter (8.8 +/-
      2.6 to 7.8 +/- 2.3 mm), gradient (7.7 +/- 8.4 to 12.6 +/- 12.2 mm Hg), or right
      ventricular pressures (43.7 +/- 9 to 47.7 +/- 10.5 mm Hg). Nine patients (16%)
      underwent scheduled stent redilation over a period of 12 days to 25 months.
      CONCLUSION: In conclusion, stent implantation shows excellent immediate and 1
      year follow-up results with maintenance of improved caliber of the stented vessel
      and lowered right ventricular systolic pressures.

PMID- 24910457
TI  - Repeated freezing induces oxidative stress and reduces survival in the freeze
      tolerant goldenrod gall fly, Eurosta solidaginis.
AB  - Freeze tolerant insects must not only survive extracellular ice formation but
      also the generation of reactive oxygen species (ROS) during oxygen reperfusion
      upon thawing. Furthermore, diurnal fluctuations in temperature place temperate
      insects at risk of being exposed to multiple freeze-thaw cycles, yet few studies
      have examined metrics of survival and oxidative stress in freeze-tolerant insects
      subjected to successive freezing events. To address this, we assessed survival in
      larvae of the goldenrod gall fly Eurosta solidaginis, after being subjected to 0,
      5, 10, 20, or 30 diurnally repeated cold exposures (RCE) to -18 degrees C or a
      single freeze to -18 degrees C for 20days. In addition, we measured indicators of
      oxidative stress, levels of cryoprotectants, and total aqueous antioxidant
      capacity in animals exposed to the above treatments at 8, 32, or 80h after their
      final thaw. Repeated freezing and thawing, rather than time spent frozen, reduced
      survival as only 30% of larvae subjected to 20 or 30 RCE successfully pupated,
      compared to those subjected to fewer RCE or a single 20d freeze, of which 82%
      pupated. RCE had little effect on the concentration of the cryoprotectant
      glycerol (4.26+/-0.66MUgglycerol.ngprotein(-1) for all treatments and time
      points) or sorbitol (18.8+/-2.9MUgsorbitol.mgprotein(-1) for all treatments and
      time points); however, sorbitol concentrations were more than twofold higher than
      controls (16.3+/-2.2MUgsorbitol.mgprotein(-1)) initially after a thaw in larvae
      subjected to a single extended freeze, but levels returned to values similar to
      controls at 80h after thaw. Thawing likely produced ROS as total aqueous
      antioxidant capacities peaked at 1.8-fold higher than controls (14.7+/
      1.6mmoltrolox.ngprotein(-1)) in animals exposed to 5, 10, or 20 RCE. By contrast,
      aqueous antioxidant capacities were similar to controls in larvae subjected to 30
      RCE or the single 20d freeze regardless of time post final thaw, indicating these
      animals may have had an impaired ability to produce primary antioxidants. Larvae
      lacking an antioxidant response also had elevated levels of oxidized proteins,
      nearly twice that of controls (21.8+/-3.2mmolchloramine-T.mgprotein(-1)).
      Repeated freezing also lead to substantial oxidative damage to lipids that was
      independent of aqueous antioxidant capacity; peroxides were, on average, 5.6-fold
      higher in larvae subjected to 10, 20 or 30 RCE compared to controls (29.1+/
      7.3mmolTMOP.MUgprotein(-1)). These data suggest that oxidative stress due to
      repeated freeze-thaw cycles reduces the capacity of E. solidaginis larvae to
      survive freezing. 

PMID- 24910459
TI  - A preliminary risk assessment of potential exposure to naturally occurring
      estrogens from Beijing (China) market milk products.
AB  - This study was conducted to determine the occurrence of the natural steroid
      hormones estrone (E1), 17alpha-estradiol (alphaE2), 17beta-estradiol (betaE2) and
      estriol (E3) in 38 commercial milk samples obtained from markets in Beijing,
      China. Liquid Chromatography coupled with tandem mass spectrometry (LC-MS/MS) was
      employed to determine estrogens levels. The concentrations of E1, alphaE2, betaE2
      and E3 in different milk products varied from 0-146.12 ng/L, 0-70.12 ng/L, 0
      31.85 ng/L to 0-2.18 ng/L, respectively. We compared exposures to estrogens
      through milk consumption with acceptable daily intakes (ADIs) and threshold for
      toxicological concern (TTC) to determine whether estrogen intakes from milk
      consumption are larger or smaller than the toxicity-based benchmarks. The
      combined margin of safety MOS (MOST) for total estrogens are about 72-99, 118
      161, 539-1104, for 2-4, 4-7 year-old residential children, and adults,
      respectively. The lowest MOST for children of 2-4 years old result from comparing
      total of estrogens with the lowest TTC value (0.15 MUg/person/day) (MOS=3.5). The
      MOS values suggest that the individual and total estrogens that may present in
      milk are not causing a health risk for the local residents, including young
      children.

PMID- 24910460
TI  - Role of CYP3A in regulating hepatic clearance and hepatotoxicity of triptolide in
      rat liver microsomes and sandwich-cultured hepatocytes.
AB  - Triptolide (TP) is an active component of Tripterygium wilfordii Hook. F and
      widely used to treat autoimmune and inflammatory diseases. It has been
      demonstrated that cytochrome P450 (CYP) are involved in the metabolism of TP.
      However, the underlying mechanisms of TP-induced toxicity mediated by hepatic CYP
      have not been well delineated. In this study, rat liver microsomes (RLM) and
      sandwich-cultured rat hepatocytes (SCRH) were used to identify the mechanism
      involving the CYP3A inhibition by TP and to evaluate TP-induced liver damage
      after CYP3A modulation by the known inhibitor, ketoconazole, and the known
      inducer, dexamethasone. The results showed that TP itself had a time- and
      concentration-dependent inhibitory effect on CYP3A. When the CYP3A inhibitor and
      inducer were added, the enzyme activity and hepatotoxicity changed significantly.
      The enzyme inducer increased CYP3A activity and decreased the metabolic half life
      (t1/2) of TP when compared to the control group, while the enzyme inhibitor had
      an opposite effect. Our findings reveal that TP is a weak CYP3A inhibitor
      involving the time-dependent inhibition mechanism. The induction or inhibition of
      CYP3A played an important role in TP-induced hepatotoxicity. Clinicians should be
      aware of the metabolic characteristics of TP to maximize therapeutic efficacy and
      reduce TP-induced toxicity. 

PMID- 24910461
TI  - Human health risk assessment and dietary intake of organochlorine pesticides
      through air, soil and food crops (wheat and rice) along two tributaries of river
      Chenab, Pakistan.
AB  - To assess the organochlorine pesticides (OCPs) contamination and their probable
      hazardous effects on human health; cereal crops (wheat and rice; n=28)
      agricultural soil (n=28) and air (n=6) samples were collected from Gujranwala
      division, Punjab Province, Pakistan. ?OCPs concentration ranged between 123 and
      635 pg m(-3), 31 and 365 ng g(-1) (dw), 2.72 and 36.6 ng g(-1) (dw), 0.55 and
      15.2 ng g(-1) (dw) for air, soil, rice and wheat samples, respectively. DDTs were
      the predominant over other OCPSs detected from screened samples while the source
      apportionment analysis suggested the new inputs of DDTs in the study area. EDI
      (estimated daily intake) of ?OCPs through rice and wheat was found 39 and 40 ng
      kg(-1) day(-1), respectively. Hazard ratios (HRs) on the basis 95th percentile
      concentrations were exceeding the integrity for most of the investigated OCP in
      rice and wheat. The results revealed that there is a severe risk to the human
      population of the study area through consumption of contaminated cereal crops.

PMID- 24910462
TI  - Best practice in nursing: a concept analysis.
AB  - BACKGROUND: Since the early 1990s a shift has occurred in the understanding of
      what constitutes quality healthcare. This is evidenced by the emergence of new
      concepts in the nursing literature, including best practice. Although authors
      have analyzed the concept of best practice in the healthcare sector, further
      analysis is required to distinguish the concept's unique meanings, and
      significance for the nursing discipline. OBJECTIVES: This paper seeks to clarify
      use of the concept of best practice in the nursing literature over the last two
      decades, and contributes to explaining its defining characteristics,
      applicability, and significance. It also distinguishes the concept's unique
      meanings and usefulness in comparison to other related terms. METHODS: An
      evolutionary concept analysis method was selected for this analysis. First, a
      representative sample of nursing sources was obtained utilizing the CINAHL
      database. This database was searched for sources in English, during the years
      1993-2013, with both best practice and nursing in the title. Data was then
      collected from the sample of retrieved literature on attributes of best practice,
      antecedent and consequential occurrences, variations, and empirical references.
      The following related concepts were also explored for purposes of comparison and
      to situate the understanding of best practice in-context: practice development,
      evidence-based practice, and standard of care. FINDINGS: Use of the concept of
      best practice in the nursing literature may be categorized into four distinct
      domains: educational, administrative, clinical and theoretical/conceptual.
      Exploration of defining attributes revealed that best practice may be
      characterized as: directive, evidence-based, and quality-focused. Antecedent
      occurrences in the sample sources were most commonly related to identification of
      a specified need or problem, somewhat defined by the domain. The implied
      consequential occurrences were ultimately better outcomes. CONCLUSION: Best
      practice is more than practice based on evidence. It represents quality care
      which is deemed optimal based on a prevailing standard or point of view. Specific
      best practices in nursing are significant because they serve to direct nurses
      regarding solutions to identified problems/needs. Continued analysis of the
      concept of best practice is required to further distinguish it from related
      concepts, and to expand our understanding of the relative meaning of best from
      multiple perspectives.

PMID- 24910463
TI  - Imaging ACL reconstructions and their complications.
AB  - Examination of ligament reconstructions, particularly of the anterior cruciate
      ligament (ACL), are common situations in everyday knee imaging practice.
      Knowledge of normal appearances, the expected changes over time and the potential
      complications of these plasties are essential. MRI is the imaging method of
      choice. This article illustrates the main complications specific to this
      procedure: suboptimal positioning of the femoral or tibial tunnels, impingement
      between the graft and bony contours, rupture (partial or complete) of the plasty
      due to friction or injury, arthrofibrosis and particularly the "Cyclops"
      syndrome, fragmentation or migration of the fixation materials and a
      granulomatous reaction to biomaterials. 

PMID- 24910464
TI  - Azithromycin inhibits MUC5AC induction via multidrug-resistant Acinetobacter
      baumannii in human airway epithelial cells.
AB  - Acinetobacter baumannii is one of the main pathogens that cause ventilator
      associated pneumonia (VAP). Hypersecretion of mucin in the airway is associated
      with the onset of VAP. Furthermore, macrolides are known to accelerate the
      resolution of VAP. However, this mechanism has not been elucidated. We examined
      whether macrolides inhibit MUC5AC production that is induced by multidrug
      resistant A. baumannii (MDRAB). MUC5AC production in bronchial cells after MDRAB
      stimulation was analyzed by enzyme-linked immunosorbent assay and quantitative
      reverse transcription-polymerase chain reaction. For the inhibition study, cells
      were treated with azithromycin (AZM) or clarithromycin (CAM) simultaneously along
      with MDRAB stimulation. Western blotting was performed was performed to determine
      potential rules for signal modules. MDRAB induced MUC5AC production and gene
      expression. The EGFR-ERK/JNK-NF-kappaB pathway was involved in MDRAB-induced
      MUC5AC production. AZM but not CAM inhibited MUC5AC production. AZM suppressed
      the phosphorylation of ERK/JNK and the nuclear translocation of NF-kappaB. Our
      results suggest that the efficacy of macrolides against VAP may be due to the
      inhibition of mucin production. 

PMID- 24910465
TI  - The memory of hunger: developmental plasticity of dietary selectivity in the
      European starling, Sturnus vulgaris.
AB  - The decision to consume toxic prey is a trade-off between the benefits of
      obtaining nutrients and the costs of ingesting toxins. This trade-off is affected
      by current state: animals will consume more toxic prey if they are food deprived.
      However, whether the trade-off is affected by developmental history is currently
      unknown. We studied the decision to eat quinine-injected mealworms in adult
      starling siblings that had been exposed to either high or low levels of food
      competition as chicks, via a brood size manipulation. At the time of our
      experiments, the two groups of birds did not differ in size, body weight or
      current environment. Each bird was presented with the toxic prey while living on
      a high-quality diet and a low-quality diet. We found an effect of diet, with
      birds consuming more toxic prey while on the low-quality diet, and also of
      developmental history, with birds from the high-competition brood size treatment
      eating more toxic prey than their low-competition siblings. The effects of brood
      size treatment were not completely mediated by early growth, although we did find
      evidence that early growth affected toxic prey consumption independently of brood
      size treatment. We discuss our results in relation to adaptive developmental
      plasticity and the developmental origins of behavioural variation.

PMID- 24910467
TI  - A Compact Shape Descriptor for Triangular Surface Meshes.
AB  - Three-dimensional shape-based descriptors have been widely used in object
      recognition and database retrieval. In the current work, we present a novel
      method called compact Shape-DNA (cShape-DNA) to describe the shape of a
      triangular surface mesh. While the original Shape-DNA technique provides an
      effective and isometric-invariant descriptor for surface shapes, the number of
      eigenvalues used is typically large. To further reduce the space and time
      consumptions, especially for large-scale database applications, it is of great
      interest to find a more compact way to describe an arbitrary surface shape. In
      the present approach, the standard Shape-DNA is first computed from the given
      mesh and then processed by surface area-based normalization and line subtraction.
      The proposed cShape-DNA descriptor is composed of some low frequencies of the
      discrete Fourier transform of the processed Shape-DNA. Several experiments are
      shown to illustrate the effectiveness and efficiency of the cShape-DNA method on
      3D shape analysis, particularly on shape comparison and classification.

PMID- 24910466
TI  - Memory, transmission and persistence of alternative foraging techniques in wild
      common marmosets.
AB  - Experimental studies on traditions in animals have focused almost entirely on the
      initial transmission phase in captive populations. We conducted an open diffusion
      field experiment with 13 groups of wild common marmosets, Callithrix jacchus.
      Seven groups contained individuals that were already familiar with the task
      ('push or pull' box) and thus served as potential models for naive individuals.
      Additionally, in four groups one individual was trained for one of the two
      possible techniques and in two control groups no skilled individuals were
      present. First, we investigated whether experienced individuals would remember
      how to solve the task even after 2 years without exposure and whether they would
      still prefer their learned technique. Second, we tested whether naive individuals
      would learn socially from their skilled family members and, more importantly,
      whether they would use the same technique. Third, we conducted several test
      blocks to see whether the individual and/or group behaviour would persist over
      time. Our results show that wild common marmosets were able to memorize, learn
      socially and maintain preferences of foraging techniques. This field experiment
      thus reveals a promising approach to studying social learning in the wild and
      provides the basis for long-term studies on tradition formation.

PMID- 24910469
TI  - Fast stray field computation on tensor grids.
AB  - A direct integration algorithm is described to compute the magnetostatic field
      and energy for given magnetization distributions on not necessarily uniform
      tensor grids. We use an analytically-based tensor approximation approach for
      function-related tensors, which reduces calculations to multilinear algebra
      operations. The algorithm scales with N4/3 for N computational cells used and
      with N2/3 (sublinear) when magnetization is given in canonical tensor format. In
      the final section we confirm our theoretical results concerning computing times
      and accuracy by means of numerical examples.

PMID- 24910468
TI  - Open Gradient Magnetic Red Blood Cell Sorter Evaluation on Model Cell Mixtures.
AB  - The emerging applications of biological cell separation to rare circulating tumor
      cell (CTC) detection and separation from blood rely on efficient methods of red
      blood cell (RBC) debulking. The two most widely used methods of centrifugation
      and RBC lysis have been associated with the concomitant significant losses of the
      cells of interest (such as progenitor cells or circulating tumor cells).
      Moreover, RBC centrifugation and lysis are not well adapted to the emerging
      diagnostic applications, relying on microfluidics and micro-scale total
      analytical systems. Therefore, magnetic RBC separation appears a logical
      alternative considering the high iron content of the RBC (normal mean 105 fg) as
      compared to the white blood cell iron content (normal mean 1.6 fg). The typical
      magnetic forces acting on a RBC are small, however, as compared to typical forces
      associated with centrifugation or the forces acting on synthetic magnetic
      nanoparticles used in current magnetic cell separations. This requires a
      significant effort in designing and fabricating a practical magnetic RBC
      separator. Applying advanced designs to the low cost, high power permanent
      magnets currently available, and building on the accumulated knowledge of the
      immunomagnetic cell separation methods and devices, an open gradient magnetic red
      blood cell (RBC) sorter was designed, fabricated and tested on label-free cell
      mixtures, with potential applications to RBC debulking from whole blood samples
      intended for diagnostic tests.

PMID- 24910470
TI  - Parameterizing the Morse Potential for Coarse-Grained Modeling of Blood Plasma.
AB  - Multiscale simulations of fluids such as blood represent a major computational
      challenge of coupling the disparate spatiotemporal scales between molecular and
      macroscopic transport phenomena characterizing such complex fluids. In this
      paper, a coarse-grained (CG) particle model is developed for simulating blood
      flow by modifying the Morse potential, traditionally used in Molecular Dynamics
      for modeling vibrating structures. The modified Morse potential is parameterized
      with effective mass scales for reproducing blood viscous flow properties,
      including density, pressure, viscosity, compressibility and characteristic flow
      dynamics of human blood plasma fluid. The parameterization follows a standard
      inverse-problem approach in which the optimal micro parameters are systematically
      searched, by gradually decoupling loosely correlated parameter spaces, to match
      the macro physical quantities of viscous blood flow. The predictions of this
      particle based multiscale model compare favorably to classic viscous flow
      solutions such as Counter-Poiseuille and Couette flows. It demonstrates that such
      coarse grained particle model can be applied to replicate the dynamics of viscous
      blood flow, with the advantage of bridging the gap between macroscopic flow
      scales and the cellular scales characterizing blood flow that continuum based
      models fail to handle adequately.

PMID- 24910471
TI  - The Influence of Dielectric Decrement on Electrokinetics.
AB  - We treat the dielectric decrement induced by excess ion polarization as a source
      of ion specificity and explore its impact on electrokinetics. We employ a
      modified Poisson-Nernst-Planck (PNP) equations accounting for the dielectric
      decrement. The dielectric decrement is determined by the excess ion polarization
      parameter alpha and when alpha = 0 the standard PNP model is recovered. Our model
      shows that ions saturate at large zeta potentials (zeta). Because of ion
      saturation, a condensed counterion layer forms adjacent to the charged surface,
      introducing a new length scale, the thickness of the condensed layer (lc ). For
      the electro-osmotic mobility, the dielectric decrement weakens the electro
      osmotic flow owing to the decrease of the dielectric permittivity. At large zeta,
      when alpha ? 0, the electro-osmotic mobility is found to be proportional to
      zeta/2, in contrast to zeta predicted by the standard PNP model. This is
      attributed to ion saturation at large zeta. In terms of the electrophoretic
      mobility Me , we carry out both an asymptotic analysis in the thin-double-layer
      limit and solve the full modified PNP model to compute Me . Our analysis reveals
      that the impact of the dielectric decrement is intriguing. At small and moderate
      zeta, the dielectric decrement decreases Me with an increasing alpha. At large
      zeta, it is well known that the surface conduction becomes significant and plays
      an important role in determining Me . It is observed that the dielectric
      decrement effectively reduces the surface conduction. Hence in stark contrast, Me
      increases as alpha increases. Our predictions of the contrast dependence of the
      mobility on alpha at different zeta potentials qualitatively agree with
      experimental results on the dependence of the mobility among ions and provide a
      possible explanation for such ion specificity. Finally, the comparisons between
      the thin-double-layer asymptotic analysis and the full simulations of the
      modified PNP model suggest that at large zeta the validity of the thin-double
      layer approximation is determined by lc rather than the traditional Debye length.

PMID- 24910472
TI  - "Where Have All the Good Men Gone?" Gendered Interactions in Online Dating.
AB  - This article explores gendered patterns of online dating and their implications
      for heterosexual union formation. The authors hypothesized that traditional
      gender norms combine with preferences for more socially desirable partners to
      benefit men and disadvantage women in the earliest stages of dating. They tested
      this with 6 months of online dating data from a mid-sized southwestern city (N =
      8,259 men and 6,274 women). They found that both men and women tend to send
      messages to the most socially desirable alters in the dating market, regardless
      of their own social desirability. They also found that women who initiate
      contacts connect with more desirable partners than those who wait to be
      contacted, but women are 4 times less likely to send messages than men. They
      concluded that socioeconomic similarities in longer term unions result, in part,
      from relationship termination (i.e., nonreciprocity) rather than initial
      preferences for similar partners.

PMID- 24910473
TI  - HOMEOWNERSHIP, HOME FORECLOSURE, AND NATIVITY: EVIDENCE FROM MIAMI-DADE COUNTY,
      FLORIDA.

PMID- 24910474
TI  - Oxidatively Responsive Chain Extension to Entangle Engineered Protein Hydrogels.
AB  - Engineering artificial protein hydrogels for medical applications requires
      precise control over their mechanical properties, including stiffness, toughness,
      extensibility and stability in the physiological environment. Here we demonstrate
      topological entanglement as an effective strategy to robustly increase the
      mechanical tunability of a transient hydrogel network based on coiled-coil
      interactions. Chain extension and entanglement are achieved by coupling the
      cysteine residues near the N- and C- termini, and the resulting chain
      distribution is found to agree with the Jacobson-Stockmayer theory. By exploiting
      the reversible nature of the disulfide bonds, the entanglement effect can be
      switched on and off by redox stimuli. With the presence of entanglements,
      hydrogels exhibit a 7.2-fold enhanced creep resistance and a suppressed erosion
      rate by a factor of 5.8, making the gels more mechanically stable in a
      physiologically relevant open system. While hardly affecting material stiffness
      (only resulting in a 1.5-fold increase in the plateau modulus), the entanglements
      remarkably lead to hydrogels with a toughness of 65,000 J m-3 and extensibility
      to approximately 3,000% engineering strain, which enables the preparation of
      tough yet soft tissue simulants. This improvement in mechanical properties
      resembles that from double-network hydrogels, but is achieved with the use of a
      single associating network and topological entanglement. Therefore, redox
      triggered chain entanglement offers an effective approach for constructing
      mechanically enhanced and responsive injectable hydrogels.

PMID- 24910475
TI  - Gender, Academics and Interscholastic Sports Participation at the School Level: A
      Gender-specific Analysis of the Relationship between Interscholastic Sports
      Participation and AP Enrollment.
AB  - While literature demonstrates that interscholastic sports participation is
      associated with positive academic outcomes, this relationship is rarely analyzed
      at a macro-level (the school-level). To date, there is no research examining
      whether increases in schools' female and male interscholastic sports
      participation rates is associated with increases in female and male AP enrollment
      rates. Using a national sample of 4,644 public high schools during the 2009-2010
      school year, we test several gender-specific hypotheses linked with the
      association between schools' sport participation rates and advanced placement
      enrollment rates (AP math, AP science, AP foreign language, and overall AP
      enrollment). The findings reveal that schools' female and male sports
      participation rates have a positive association with schools' female and male AP
      math, AP science, AP foreign language, and overall AP enrollment rates. Moreover,
      the findings suggest that females benefit more than males in regard to the
      positive relationship between interscholastic sports and AP enrollment.

PMID- 24910476
TI  - Baeyer-Villiger Rearrangement of a Substituted Pyrrole by Oxone.
AB  - Pyrroloxyls have been reported to exhibit very narrow EPR spectral lines,
      essential for in vivo imaging. En route to pyrroloxyls, we observed an unexpected
      Baeyer-Villiger rearrangement, leading to loss of aromaticity and formation of a
      4,5-dihydro-1H-ketopyrrole.

PMID- 24910477
TI  - Money for nothing: How firms have financed R&D-projects since the Industrial
      Revolution.
AB  - We investigate the long-run historical pattern of R&D-outlays by reviewing
      aggregate growth rates and historical cases of particular R&D projects, following
      the historical-institutional approach of Chandler (1962), North (1981) and
      Williamson (1985). We find that even the earliest R&D-projects used non
      insignificant cash outlays and that until the 1970s aggregate R&D outlays grew
      far faster than GDP, despite five well-known challenges that implied that R&D
      could only be financed with cash, for which no perfect market existed: the
      presence of sunk costs, real uncertainty, long time lags, adverse selection, and
      moral hazard. We then review a wide variety of organisational forms and
      institutional instruments that firms historically have used to overcome these
      financing obstacles, and without which the enormous growth of R&D outlays since
      the nineteenth century would not have been possible.

PMID- 24910478
TI  - Social Reactions to Sexual Assault Disclosure, Coping, Perceived Control and PTSD
      Symptoms in Sexual Assault Victims.
AB  - The social reactions that sexual assault victims receive when they disclose their
      assault have been found to relate to posttraumatic stress disorder (PTSD)
      symptoms. Using path analysis and a large sample of sexual assault survivors (N =
      1863), we tested whether perceived control, maladaptive coping, and social and
      individual adaptive coping strategies mediated the relationships between social
      reactions to disclosure and PTSD symptoms. We found that positive social
      reactions to assault disclosure predicted greater perceived control over
      recovery, which in turn was related to less PTSD symptoms. Positive social
      reactions to assault disclosure were also associated with more adaptive social
      and individual coping; however, only adaptive social coping predicted PTSD
      symptoms. Negative social reactions to assault disclosure were related to greater
      PTSD symptoms both directly and indirectly through maladaptive coping and
      marginally through lower perceived control over recovery.

PMID- 24910479
TI  - Explorations into the Synergy Between Faith, Health, and Health-Care Among Black
      Baptists.
AB  - BACKGROUND: U.S. health disparities are documented by race/ethnic, socioeconomic,
      gender, and geographic demographics. Since federal health record keeping began,
      regardless of other demographic factors, Black people continue to record
      statistical significant disparities. The complementary and alternative medicine
      (CAM) domain of mind-body medicine provides a method and language to assess the
      metaphysical constructs of faith, spirituality and religion and their influence
      on health and healthcare practices. Explorations into the synergy between faith,
      health and healthcare among a convenient sample of Black Baptist conventioneers
      provides an opportunity to better understand if and how faith can be used to
      enhance the health and wellbeing of Black people. METHODOLOGY: In 2005 a
      convenience sample of 2,500 Black persons among 10,000 Joint Baptist
      conventioneers participated in the study; 1,827 completed and returned an 80 item
      questionnaire. 500 surveys were lost due to computer malfunctions. Survey results
      covered: demographic, health/safety, health care, and faith/religion/health.
      RESULTS: 58.6% of respondents were women; 61% were married. Most (66.2%) reported
      good health and few were told by their physician they had a chronic disease.
      33.5% never talk to their pastor about health problems or (42.7%) physician
      visits. Mental health responses: (98.7%) get along well with others; (93.6%) were
      satisfied with life; (92.8%) feel good about themselves; and (97.6%) were in good
      spirits most times. Many were in social organizations (40.6%). 96.1% felt
      religion was very important in their life; 91% thought religion affects
      physical/mental health; and 89.1% believed faith affects mental/physical health.
      95.7% believe faith can change a health crisis. Most described religion and faith
      differently. DISCUSSION: The Black Church has history in social justice connected
      to community health. Responses to religion/faith affirm the interconnectedness of
      the synergy between faith-health. Empowered by religious fervor to interpret
      their health status as positive; they must also balance perceptions with evidence
      based health decision-making, health practices, and sustained healthcare
      utilization. CONCLUSION: A thoughtful scrutiny of the constructs of health and
      healthcare enable a new paradigm - Optimal Health - to emerge The Black Church
      has and must forever be the institution that helps Black people to continue to
      grow and develop in journeying to reach their best possible emotional,
      intellectual, physical, spiritual, and socioeconomic greatest state of aliveness,
      which is Optimal Health. In order to maximize the synergy between faith, health
      and health care; individuals, groups, and communities must harmonize physical,
      social, psychological, and spiritual well-being. The spiritual component can
      serve as the foundation on which the other three components rest. Considering
      many in this study who attended church or religious services three (3) or more
      times within the past 30 days and they rarely talked to their pastor concerning
      health problems or what their physician told them; the religious/church service
      through sermons, Sunday school, Bible class and various ministries can serve as a
      platform for health promotion in the Black Church and the larger Black community.

PMID- 24910480
TI  - WHICH CRIMINOGENIC NEED CHANGES ARE MOST IMPORTANT IN PROMOTING DESISTANCE FROM
      CRIME AND SUBSTANCE USE?
AB  - Andrews and Bonta identified the following criminogenic needs as important to
      reducing offending: substance use, antisocial cognition, antisocial associates,
      family and marital relations, employment, and leisure and recreational
      activities. This study examines dynamic criminogenic need changes across a 12
      month period and identifies which need changes are the best predictors of
      criminal offending and illicit drug use among a sample of drug-involved
      probationers who participated in an intervention (N = 251). Probationers had
      significant changes in several need areas, and treatment participation moderated
      some changes. Probationers who had reductions in criminally involved family
      members they associate with, improved work performance, and decreased alcohol use
      had the greatest reductions in offending. Those who increased time spent engaged
      in leisure and recreational activities were less likely to self-report subsequent
      drug use. These findings suggest that certain dynamic need changes may be more
      important than others, and designing interventions to impact these needs might
      improve outcomes.

PMID- 24910482
TI  - Enjoying the high life-drugs in history and culture.

PMID- 24910481
TI  - Who Benefits from Gender Responsive Treatment? Accounting for Abuse History on
      Longitudinal Outcomes for Women in Prison.
AB  - This study explores outcome variation among women offenders who participated in
      gender-responsive substance abuse treatment (GRT). In order to identify subgroups
      of participants that may differentially benefit from this treatment, secondary
      analyses examined the interaction between randomization into GRT and a history of
      abuse (physical/sexual) on depression and number of substances used post-
      treatment. The sample consisted of 115 incarcerated women assessed at baseline
      and 6- and 12-months post parole. Longitudinal regression showed that women
      reporting abuse randomized into GRT had significantly reduced odds of depression
      (OR = .29, p < .05, 95% CI = .10 - .86) and lowered rates of number of substances
      used (IRR = .52, p < .05, 95% CI = 0.28-0.98), in comparison to those who
      reported abuse and were randomized to the non-GRT group. GRT for women offenders
      who have experienced prior abuse would maximize the benefits of the trauma
      informed, gender-sensitive intervention.

PMID- 24910483
TI  - Selective Narrowing of Social Networks Across Adulthood is Associated With
      Improved Emotional Experience in Daily Life.
AB  - Past research has documented age differences in the size and composition of
      social networks that suggest that networks grow smaller with age and include an
      increasingly greater proportion of well-known social partners. According to
      socioemotional selectivity theory, such changes in social network composition
      serve an antecedent emotion regulatory function that supports an age-related
      increase in the priority that people place on emotional well-being. The present
      study employed a longitudinal design with a sample that spanned the full adult
      age range to examine whether there is evidence of within-individual
      (developmental) change in social networks and whether the characteristics of
      relationships predict emotional experiences in daily life. Using growth curve
      analyses, social networks were found to increase in size in young adulthood and
      then decline steadily throughout later life. As postulated by socioemotional
      selectivity theory, reductions were observed primarily in the number of
      peripheral partners; the number of close partners was relatively stable over
      time. In addition, cross-sectional analyses revealed that older adults reported
      that social network members elicited less negative emotion and more positive
      emotion. The emotional tone of social networks, particularly when negative
      emotions were associated with network members, also predicted experienced emotion
      of participants. Overall, findings were robust after taking into account
      demographic variables and physical health. The implications of these findings are
      discussed in the context of socioemotional selectivity theory and related
      theoretical models.

PMID- 24910484
TI  - Determining the relevance of different aspects of formant contours to
      intelligibility.
AB  - Previous studies have shown that "clear" speech, where the speaker intentionally
      tries to enunciate, has better intelligibility than "conversational" speech,
      which is produced in regular conversation. However, conversational and clear
      speech vary along a number of acoustic dimensions and it is unclear what aspects
      of clear speech lead to better intelligibility. Previously, Kain et al. [J.
      Acoust. Soc. Am. 124 (4), 2308-2319 (2008)] showed that a combination of short
      term spectra and duration was responsible for the improved intelligibility of one
      speaker. This study investigates subsets of specific features of short-term
      spectra including temporal aspects. Similar to Kain's study, hybrid stimuli were
      synthesized with a combination of features from clear speech and complementary
      features from conversational speech to determine which acoustic features cause
      the improved intelligibility of clear speech. Our results indicate that, although
      steady-state formant values of tense vowels contributed to the intelligibility of
      clear speech, neither the steady-state portion nor the formant transition was
      sufficient to yield comparable intelligibility to that of clear speech. In
      contrast, when the entire formant contour of conversational speech including the
      phoneme duration was replaced by that of clear speech, intelligibility was
      comparable to that of clear speech. It indicated that the combination of formant
      contour and duration information was relevant to the improved intelligibility of
      clear speech. The study provides a better understanding of the relevance of
      different aspects of formant contours to the improved intelligibility of clear
      speech.

PMID- 24910485
TI  - Cancer diagnosis by nuclear morphometry using spatial information .
AB  - Methods for extracting quantitative information regarding nuclear morphology from
      histopathology images have been long used to aid pathologists in determining the
      degree of differentiation in numerous malignancies. Most methods currently in
      use, however, employ the naive Bayes approach to classify a set of nuclear
      measurements extracted from one patient. Hence, the statistical dependency
      between the samples (nuclear measurements) is often not directly taken into
      account. Here we describe a method that makes use of statistical dependency
      between samples in thyroid tissue to improve patient classification accuracies
      with respect to standard naive Bayes approaches. We report results in two sample
      diagnostic challenges.

PMID- 24910486
TI  - Variable Assessment in Latent Class Models.
AB  - The latent class model provides an important platform for jointly modeling mixed
      mode data - i.e., discrete and continuous data with various parametric
      distributions. Multiple mixed-mode variables are used to cluster subjects into
      latent classes. While the mixed-mode latent class analysis is a powerful tool for
      statisticians, few studies are focused on assessing the contribution of mixed
      mode variables in discriminating latent classes. Novel measures are derived for
      assessing both absolute and relative impacts of mixed-mode variables in latent
      class analysis. Specifically, the expected posterior gradient and the Kolmogorov
      variation of the posterior distribution, as well as related properties are
      studied. Numerical results are presented to illustrate the measures.

PMID- 24910487
TI  - Choice of conflict resolution strategy is linked to sociability in dog puppies.
AB  - Measures that are likely to increase sociability in dog puppies, such as
      appropriate socialisation, are considered important in preventing future fear or
      aggression related problems. However, the interplay between sociability and
      conflict behaviour has rarely been investigated. Moreover, while many studies
      have addressed aggression in domestic dogs, alternative, non-aggressive conflict
      resolution strategies have received less scientific attention. Here we tested 134
      Border collie puppies, aged 40-50 days, in a personality test which included
      friendly interactions with an unfamiliar person, exposure to a novel object, and
      three brief restraint tests. Considering the latter to be mild 'conflict'
      situations, we analysed whether the puppies' behaviour in the restraint tests was
      related to their sociability or to their boldness towards the novel object.
      Strategies employed by the puppies during restraint tests included trying to
      interact socially with the experimenter, remaining passive, and attempting to
      move away. In line with findings from humans and goats, puppies scoring high on
      sociability were more likely to adopt an interactive conflict resolution
      strategy, while those with low sociability scores tended to react passively. In
      contrast, avoidance behaviours were unrelated to sociability, possibly reflecting
      inconsistency in the flight strategy in dogs. Boldness towards a novel object was
      not related to sociability or to puppies' reactions in restraint tests. This is
      one of the first studies to demonstrate a link between sociability and conflict
      resolution strategies in non-human animals.

PMID- 24910488
TI  - Exploring the role of Natural Helpers in efforts to address disparities for
      children with conduct problems.
AB  - The incorporation of natural helpers into services has been suggested as an
      innovative strategy to address disparities for historically underserved children
      with conduct problems. In order to inform incorporation efforts, this study
      examined the perceptions of natural helpers serving one U.S. Latina/o community
      regarding need for services for children with conduct problems, their reactions
      to a specific parent training intervention, and the training and support needed
      to deliver this intervention successfully. Participants identified a need for
      culturally-responsive services for children with conduct problems, and felt that
      parent training would be appropriate for the families they serve. Participants
      further identified specific training and support that they would require in order
      to deliver parent training with fidelity and effectiveness. Findings support the
      suggestion that natural helpers have the potential to address service disparities
      among Latina/o children with conduct problems. Recommendations from natural
      helpers should guide the development of culturally-adapted preventive
      interventions that help address existing service disparities.

PMID- 24910489
TI  - A General Class of Test Statistics for Van Valen's Red Queen Hypothesis.
AB  - Van Valen's Red Queen hypothesis states that within a homogeneous taxonomic group
      the age is statistically independent of the rate of extinction. The case of the
      Red Queen hypothesis being addressed here is when the homogeneous taxonomic group
      is a group of similar species. Since Van Valen's work, various statistical
      approaches have been used to address the relationship between taxon age and the
      rate of extinction. We propose a general class of test statistics that can be
      used to test for the effect of age on the rate of extinction. These test
      statistics allow for a varying background rate of extinction and attempt to
      remove the effects of other covariates when assessing the effect of age on
      extinction. No model is assumed for the covariate effects. Instead we control for
      covariate effects by pairing or grouping together similar species. Simulations
      are used to compare the power of the statistics. We apply the test statistics to
      data on Foram extinctions and find that age has a positive effect on the rate of
      extinction. A derivation of the null distribution of one of the test statistics
      is provided in the supplementary material.

PMID- 24910490
TI  - Exploring salutogenic mechanisms of an outdoor experiential learning programme on
      youth care farms in the Netherlands: untapped potential?
AB  - This study explored how (learning) experiences offered through outdoor
      experiential programmes, particularly the youth care farm approach, may (or may
      not) enhance young peoples' ability to recognise and then utilise available
      resources for personal growth, protection and health promotion. A total of 11
      youngsters were asked to look back on their half-year stay on a care farm in the
      Netherlands, by using semi-structured interviews to elicit their experiences from
      a salutogenic perspective. Analysis revealed that several resources (and the
      interaction of these resources) on the youth care farm worked well for the
      youngsters; contributed to their personal development and to their sense of
      coherence: the feeling that the world is or can be meaningful, comprehensible and
      manageable, associated with positive outcome in endeavours linked to improving
      health and well-being. In general, the attitude of the farmer, working with
      animals, the informal atmosphere and being temporarily cut-off from the former
      environment were elements most positively highlighted by the youngsters. The farm
      environment was mentioned as calming, however, as structuring as well. The
      strength of the programme as an experiential learning opportunity appears to be
      the diversity and richness of resources (and stressors!) available to the
      participants. This creates various opportunities for learning: making sense,
      interpreting and giving meaning to resources and stressors. Further research into
      the impact of this kind of programmes, compared to more 'traditional' programmes,
      especially on the ability of youngsters to use resources to finish school, find
      employment and develop better relationships with their parents is recommended.

PMID- 24910491
TI  - Managing stress: the influence of gender, age and emotion regulation on coping
      among university students in Botswana.
AB  - This study focused on the influence of gender, age and emotion regulation on
      coping strategies among university students in Botswana. Sixty-four males and 64
      females, ranging in age from 18 to 29 years completed the Difficulty in Emotion
      Regulation Scale and the Coping Strategy Inventory. Female students used wishful
      thinking and problem-focused disengagement more than male students; however,
      there were no other significant gender differences in coping strategies. Older
      students were more likely to use problem-solving, cognitive restructuring and
      express emotion coping strategies. In addition, problems in emotion regulation
      significantly predicted problem-and emotion-focused engagement, problem- and
      emotion-focused disengagement and coping strategies. There was a unique finding
      that non-acceptance of emotional responses, a type of emotion suppression, was
      positively correlated with problem solving, cognitive restructuring, expressing
      emotion, social support, problem avoidance and wishful thinking coping
      strategies. Cultural context and implications for student well-being and
      university support are discussed.

PMID- 24910492
TI  - Photofragmentation of Gas-Phase Lanthanide Cyclopentadienyl Complexes:
      Experimental and Time-Dependent Excited-State Molecular Dynamics.
AB  - Unimolecular gas-phase laser-photodissociation reaction mechanisms of open-shell
      lanthanide cyclopentadienyl complexes, Ln(Cp)3 and Ln(TMCp)3, are analyzed from
      experimental and computational perspectives. The most probable pathways for the
      photoreactions are inferred from photoionization time-of-flight mass spectrometry
      (PI-TOF-MS), which provides the sequence of reaction intermediates and the
      distribution of final products. Time-dependent excited-state molecular dynamics
      (TDESMD) calculations provide insight into the electronic mechanisms for the
      individual steps of the laser-driven photoreactions for Ln(Cp)3. Computational
      analysis correctly predicts several key reaction products as well as the observed
      branching between two reaction pathways: (1) ligand ejection and (2) ligand
      cracking. Simulations support our previous assertion that both reaction pathways
      are initiated via a ligand-to-metal charge-transfer (LMCT) process. For the more
      complex chemistry of the tetramethylcyclopentadienyl complexes Ln(TMCp)3, TMESMD
      is less tractable, but computational geometry optimization reveals the structures
      of intermediates deduced from PI-TOF-MS, including several classic "tuck-in"
      structures and products of Cp ring expansion. The results have important
      implications for metal-organic catalysis and laser-assisted metal-organic
      chemical vapor deposition (LCVD) of insulators with high dielectric constants.

PMID- 24910493
TI  - Intrinsic and extrinsic drivers of succession: Effects of habitat age and season
      on an aquatic insect community.
AB  - 1. Classical studies of succession, largely dominated by plant community studies,
      focus on intrinsic drivers of change in community composition, such as
      interspecific competition and changes to the abiotic environment. They often do
      not consider extrinsic drivers of colonization, such as seasonal phenology, that
      can affect community change. 2. We investigated both intrinsic and extrinsic
      drivers of succession for dipteran communities that occupy ephemeral pools, such
      as those in artificial containers. By initiating communities at different times
      in the season and following them over time, we compared the relative importance
      of intrinsic (i.e., habitat age) vs. extrinsic (i.e., seasonal phenology) drivers
      of succession. 3. We placed water-filled artificial containers in a deciduous
      forest with 20 containers initiated in each of three months. Containers were
      sampled weekly to assess community composition. Repeated-measures mixed-effects
      analysis of community correspondence analysis (CA) scores enabled us to partition
      intrinsic and extrinsic effects on succession. Covariates of temperature and
      precipitation were also tested. 4. Community trajectories (as defined by CA)
      differed significantly with habitat age and season, indicating that both
      intrinsic and extrinsic effects influence succession patterns. Comparisons of
      AICcs showed that habitat age was more important than season for species
      composition. Temperature and precipitation did not explain composition changes
      beyond those explained by habitat age and season. 5. Quantification of relative
      strengths of intrinsic and extrinsic effects on succession in dipteran and other
      ephemeral communities enables us to disentangle processes that must be understood
      for predicting changes in community composition.

PMID- 24910494
TI  - Ambivalent Sexism and Religion: Connected Through Values.
AB  - Sexist attitudes do not exist in a limbo; they are embedded in larger belief
      systems associated with specific hierarchies of values. In particular,
      manifestations of benevolent sexism (Glick and Fiske 1996, 1997, 2001) can be
      perceived as a social boon, not a social ill, both because they are experienced
      as positive, and because they reward behaviors that maintain social stability.
      One of the strongest social institutions that create and justify specific
      hierarchies of values is religion. In this paper, we examine how the values
      inherent in religious beliefs (perhaps inadvertently) propagate an unequal status
      quo between men and women through endorsement of ideologies linked to benevolent
      sexism. In a survey with a convenience sample of train passengers in Southern and
      Eastern Poland (N = 180), we investigated the relationship between Catholic
      religiosity and sexist attitudes. In line with previous findings (Gaunt 2012;
      Glick et al. 2002a; Tasdemir and Sakalli-Ugurlu 2010), results suggest that
      religiosity can be linked to endorsement of benevolent sexism. This relationship
      was mediated in our study by the values of conservatism and openness to change
      (Schwartz 1992): religious individuals appear to value the societal status quo,
      tradition, and conformity, which leads them to perceive women through the lens of
      traditional social roles. Adhering to the teachings of a religion that promotes
      family values in general seems to have as its byproduct an espousal of
      prejudicial attitudes toward specific members of the family.

PMID- 24910495
TI  - The New Homelessness Revisited.
AB  - The 'new homelessness' has drawn sustained attention from scholars over the past
      three decades. Definitional inconsistencies and data limitations rendered early
      work during this period largely speculative in nature. Thanks to conceptual,
      theoretical, and methodological progress, however, the research literature now
      provides a fuller understanding of homelessness. Contributions by sociologists
      and other social scientists since the mid-1990s differentiate among types of
      homelessness, provide credible demographic estimates, and show how being homeless
      affects a person's life chances and coping strategies. Agreement also exists
      about the main macro- and micro-level causes of homelessness. Active lines of
      inquiry examine public, media, and governmental responses to the problem as well
      as homeless people's efforts to mobilize on their own behalf. Despite the
      obstacles faced when studying a stigmatized population marked by high turnover
      and weak anchors to place, recent investigations have significantly influenced
      homelessness policy. A greater emphasis on prevention should further strengthen
      the research-policy nexus.

PMID- 24910496
TI  - CYCLOADDITION REACTIONS OF AZIDE, FURAN, AND PYRROLE UNITS WITH BENZYNES
      GENERATED BY THE HEXADEHYDRO-DIELS-ALDER (HDDA) REACTION.
AB  - Benzynes can be generated by the intramolecular thermal cycloisomerization of
      triynes-the title HDDA reaction. We report here that these can be trapped by
      cycloaddition reaction with trimethylsilyl azide (1,3-dipolar) or a furan or
      pyrrole (4+2 Diels-Alder).

PMID- 24910497
TI  - Bigger is Not Better: Effects of Hearing Loss on Central Processing.

PMID- 24910498
TI  - The difference between "giving a rose" and "giving a kiss": Sustained neural
      activity to the light verb construction.
AB  - We used event-related potentials (ERPs) to investigate the neurocognitive
      mechanisms associated with processing light verb constructions such as "give a
      kiss". These constructions consist of a semantically underspecified light verb
      ("give") and an event nominal that contributes most of the meaning and also
      activates an argument structure of its own ("kiss"). This creates a mismatch
      between the syntactic constituents and the semantic roles of a sentence. Native
      speakers read German verb-final sentences that contained light verb constructions
      (e.g., "Julius gave Anne a kiss"), non-light constructions (e.g., "Julius gave
      Anne a rose"), and semantically anomalous constructions (e.g., *"Julius gave Anne
      a conversation"). ERPs were measured at the critical verb, which appeared after
      all its arguments. Compared to non-light constructions, the light verb
      constructions evoked a widely distributed, frontally focused, sustained negative
      going effect between 500 and 900 ms after verb onset. We interpret this effect as
      reflecting working memory costs associated with complex semantic processes that
      establish a shared argument structure in the light verb constructions.

PMID- 24910499
TI  - Attentional Control in Early and Later Bilingual Children.
AB  - This study examined differences in attentional control among school-age children
      who were monolingual English speakers, early childhood Spanish-English bilinguals
      who began speaking both languages by age 3, and later childhood Spanish-English
      bilingual children who began speaking English after age 3. Children's attentional
      control was tested using the Attention Network Test (ANT). All language groups
      performed equally on ANT networks; however, when controlling for age and verbal
      ability, groups differed significantly on reaction time. Early bilingual children
      responded faster on the ANT compared to both monolingual and later bilingual
      children, suggesting an attentional monitoring advantage for early bilinguals.
      These results add to mounting evidence of advantaged cognitive functioning among
      bilinguals, and are consistent with the possibility that children who begin
      speaking a second language earlier in childhood have larger advantages due either
      to differential effects of acquiring a second language earlier during development
      or due to longer duration of bilingual experience.

PMID- 24910500
TI  - The Relationship of Hoarding Symptoms to Schizotypal Personality and Cognitive
      Schemas in an OCD Sample.

PMID- 24910501
TI  - "As Good As It Gets": Undocumented Latino Day Laborers Negotiating Discrimination
      in San Francisco and Berkeley, California, USA.
AB  - Undocumented Latino day laborers in the United States are vulnerable to being
      arrested and expelled at any time. This social fact shapes their everyday lives
      in terms of actions taken and strategies deployed to mitigate being confronted,
      profiled, and possibly incarcerated and deported. While perceptions of threat and
      bouts of discrimination are routine among undocumented Latino day laborers, their
      specific nature vary according to multiple social factors and structural forces
      that differ significantly from locale to locale. The experience of discrimination
      is often tacitly negotiated through perceptions, decisions, and actions toward
      avoiding or moderating its ill effects. This essay examines urban undocumented
      Latino day laborers over a variety of sites in the greater San Francisco Bay
      Area, which, compared to many metropolitan areas in the U.S. is "as good as it
      gets" in terms of being socially tolerated and relatively safe from persecution.
      Nonetheless, tacit negotiations are necessary to withstand or overcome challenges
      presented by idiosyncratic and ever changing global, national/state, and local
      dynamics of discrimination. [undocumented Latino laborers, social exclusion,
      discrimination, tacit negotiation].

PMID- 24910502
TI  - Reliability, Validity, and Item Response of MOS Social Support Score among
      Incarcerated Women.

PMID- 24910503
TI  - Selected Topics on the Synthesis, Properties and Applications of Multiwalled
      Carbon Nanotubes.
AB  - In summary, MWCNTs have been examined for a variety of electronic applications
      due to their unique structure and chemistry. Electrodes for field emission,
      energy and sensor applications hold particular interest. MWCNTs provide a very
      high surface area, relatively easy methods of surface modification, controllable
      and high concentration of reactive surface sites, and high specific capacitance.
      Combining MWCNTs with graphene structures, oxide and metal nanoparticles and
      certain polymers extends their performance and functionality. Such hybrid
      structures have been produced in situ during CNT growth and in two-step
      processes. Excellent progress on understanding the mechanisms of CNT growth has
      enabled numerous growth methods to all yield MWCNT structures in a variety of
      morphologies.

PMID- 24910504
TI  - Intensive Interventions in Reading for Students with Reading Disabilities:
      Meaningful Impacts.
AB  - We use three data sources to build a rationale for why intensive interventions
      are necessary for students with pervasive reading disabilities: current data on
      the performance of students with disabilities on reading achievement measures
      over time, observation studies on students with reading disabilities in general
      and special education classrooms, and findings from intensive intervention
      studies for students with reading disabilities. Results of these data sources
      indicate that students with disabilities are not making progress in reading at
      the same rate as students without disabilities, reading instruction for students
      with reading disabilities is comprised of excessive amounts of low level tasks,
      and findings from intensive intervention studies suggest positive impacts for
      students with reading disabilities. We argue that students with reading
      disabilities require ongoing intensive interventions that are likely to require
      schools to change the contexts and practices for these students.

PMID- 24910505
TI  - Environmental Public Health Applications Using Remotely Sensed Data.
AB  - We describe a remote sensing and GIS-based study that has three objectives: (1)
      characterize fine particulate matter (PM2.5), insolation and land surface
      temperature using NASA satellite observations, EPA ground-level monitor data and
      North American Land Data Assimilation System (NLDAS) data products on a national
      scale; (2) link these data with public health data from the REasons for
      Geographic And Racial Differences in Stroke (REGARDS) national cohort study to
      determine whether these environmental risk factors are related to cognitive
      decline, stroke and other health outcomes; and (3) disseminate the environmental
      datasets and public health linkage analyses to end users for decision-making
      through the Centers for Disease Control and Prevention (CDC) Wide-ranging Online
      Data for Epidemiologic Research (WONDER) system. This study directly addresses a
      public health focus of the NASA Applied Sciences Program, utilization of Earth
      Sciences products, by addressing issues of environmental health to enhance public
      health decision-making.

PMID- 24910506
TI  - Analysis of scalability of high-performance 3D image processing platform for
      virtual colonoscopy.
AB  - One of the key challenges in three-dimensional (3D) medical imaging is to enable
      the fast turn-around time, which is often required for interactive or real-time
      response. This inevitably requires not only high computational power but also
      high memory bandwidth due to the massive amount of data that need to be
      processed. For this purpose, we previously developed a software platform for high
      performance 3D medical image processing, called HPC 3D-MIP platform, which
      employs increasingly available and affordable commodity computing systems such as
      the multicore, cluster, and cloud computing systems. To achieve scalable high
      performance computing, the platform employed size-adaptive, distributable block
      volumes as a core data structure for efficient parallelization of a wide range of
      3D-MIP algorithms, supported task scheduling for efficient load distribution and
      balancing, and consisted of a layered parallel software libraries that allow
      image processing applications to share the common functionalities. We evaluated
      the performance of the HPC 3D-MIP platform by applying it to computationally
      intensive processes in virtual colonoscopy. Experimental results showed a 12-fold
      performance improvement on a workstation with 12-core CPUs over the original
      sequential implementation of the processes, indicating the efficiency of the
      platform. Analysis of performance scalability based on the Amdahl's law for
      symmetric multicore chips showed the potential of a high performance scalability
      of the HPC 3D-MIP platform when a larger number of cores is available.

PMID- 24910507
TI  - Movement Forms: A Graph-Dynamic Perspective.
AB  - The focus of this paper is on characterizing the physical movement forms (e.g.,
      walk, crawl, roll, etc.) that can be used to actualize abstract, functionally
      specified behavioral goals (e.g., locomotion). Emphasis is placed on how such
      forms are distinguished from one another, in part, by the set of topological
      patterns of physical contact between agent and environment (i.e., the set of
      physical graphs associated with each form) and the transitions among these
      patterns displayed over the course of performance (i.e., the form's physical
      graph dynamics). Crucial in this regard is the creation and dissolution of loops
      in these graphs, which can be related to the distinction between open and closed
      kinematic chains. Formal similarities are described within the theoretical
      framework of task-dynamics between physically-closed kinematic chains (physical
      loops) that are created during various movement forms and functionally-closed
      kinematic chains (functional loops) that are associated with task-space control
      of end-effectors; it is argued that both types of loop must be flexibly
      incorporated into the coordinative structures that govern skilled action. Final
      speculation is focused on the role of graphs and their dynamics, not only in
      processes of coordination and control for individual agents, but also in
      processes of inter-agent coordination and the coupling of agents with (non
      sentient) environmental objects.

PMID- 24910508
TI  - Innovations in the Identification and Referral of Mothers at Risk for Depression:
      Development of a Peer-to-Peer Model.
AB  - This paper describes a feasibility study of a peer-delivered prevention
      intervention to identify mothers at high risk for depression and facilitate
      engagement in mental health services for their emotional health. Sixteen family
      peer advocates and their supervisors partnered with academic researchers over a
      period of six months to develop a four-session intervention that focused on
      identifying symptoms of depression, providing education about depression and
      treatment, actively linking caregivers to treatment for their own emotional
      health, and assisting caregivers in becoming active participants in their mental
      health care. Collaborating with peers to develop the model enhanced its perceived
      relevance and utility, and resulted in an intervention that was complimentary to
      their roles and the mission of peer-delivered support services. Peer/professional
      partnerships may be beneficial for enhancing the feasibility and acceptability of
      research efforts; the impact of peers' participation in the current project and
      the need for future research to develop and study peer-delivered models is
      discussed.

PMID- 24910509
TI  - Grazing Effects on Deer Mice with Implications to Human Exposure to Sin Nombre
      Virus.
AB  - We examined the effects of grazing on deer mouse (Peromyscus maniculatus)
      movements into buildings using passive integrated transponder (PIT) technology
      and small simulated buildings located on 0.6-ha treatment (grazing) and control
      (no grazing) plots. Twelve experimental 9-day trials were conducted over the
      course of the study. During these trials, mouse movements into buildings were
      monitored during three time periods (each 3 days in length). In the treatment
      plots these time periods corresponded to pre-grazing, grazing, and post grazing
      by horses. The number of individual deer mice entering buildings over time
      decreased in both the grazed and control plots during the 9 days of each
      experiment. The number of entrances per/individual among the pre-grazing, grazing
      and post grazing periods was different between control and treated plots for both
      males and females. The distribution of entrances/individual among the three
      periods differed between males and females in both grazed and control plots. The
      habitat modification caused by grazing appeared to reduce deer mouse activity
      (entrances/individual) in buildings but does not affect the number of mice
      entering buildings. Reducing vegetative cover by grazing or mowing may not affect
      the number of mice investigating small structures but grazing creates different
      activity patterns in the structures for neighboring deer mice.

PMID- 24910510
TI  - Phases in development of an interactive mobile phone-based system to support self
      management of hypertension.
AB  - Hypertension is a significant risk factor for heart disease and stroke worldwide.
      Effective treatment regimens exist; however, treatment adherence rates are poor
      (30%-50%). Improving self-management may be a way to increase adherence to
      treatment. The purpose of this paper is to describe the phases in the development
      and preliminary evaluation of an interactive mobile phone-based system aimed at
      supporting patients in self-managing their hypertension. A person-centered and
      participatory framework emphasizing patient involvement was used. An
      interdisciplinary group of researchers, patients with hypertension, and health
      care professionals who were specialized in hypertension care designed and
      developed a set of questions and motivational messages for use in an interactive
      mobile phone-based system. Guided by the US Food and Drug Administration
      framework for the development of patient-reported outcome measures, the
      development and evaluation process comprised three major development phases (1,
      defining; 2, adjusting; 3, confirming the conceptual framework and delivery
      system) and two evaluation and refinement phases (4, collecting, analyzing,
      interpreting data; 5, evaluating the self-management system in clinical
      practice). Evaluation of new mobile health systems in a structured manner is
      important to understand how various factors affect the development process from
      both a technical and human perspective. Forthcoming analyses will evaluate the
      effectiveness and utility of the mobile phone-based system in supporting the self
      management of hypertension. 

PMID- 24910511
TI  - Aortic stiffness: pathophysiology, clinical implications, and approach to
      treatment.
AB  - Aortic stiffness is a hallmark of aging, and classic cardiovascular risk factors
      play a role in accelerating this process. Current changes in medicine, which
      focus on preventive care, have led to a growing interest in noninvasive
      evaluation of aortic stiffness. Aortic stiffness has emerged as a good tool for
      further risk stratification because it has been linked to increased risk of
      atherosclerotic heart disease, myocardial infarction, heart failure, and stroke.
      This has led to the invention and validation of multiple methods to measure
      aortic stiffness. Pulse wave velocity is emerging as the gold standard for
      evaluation of aortic stiffness. This review focuses on the pathophysiology
      involved in aortic stiffness, methods available for evaluation of aortic
      stiffness, the importance of central pressure as a predictor of future
      cardiovascular events, and therapies that affect aortic stiffness. 

PMID- 24910512
TI  - Developing an alcohol education leaflet for pregnant women using qualitative and
      quantitative data.
AB  - OBJECTIVE: This article summarizes the process of developing and evaluating a
      series of alcohol educational leaflets with pregnant women. METHODS: Four group
      interviews were conducted with a total of 33 pregnant women. RESULTS: The copy,
      font, and color should be tailored to pregnant women. Scientifically compelling
      information was preferred; the use of too many colors and objects was considered
      distracting and reducing the seriousness of the information. The facts presented
      through a patient's photo of fetal alcohol syndrome and a graph impressed the
      participants, since they were tired of the illustrations found in many other
      materials. Pregnant women who are interested and motivated to learn about alcohol
      consumption valued the quality of the information, rather than visual appeal.
      CONCLUSIONS: Testing a draft leaflet with the target population before final
      development and dissemination is a critical component of an educational outreach
      effort. Incorporating feedback can help enhance the quality of the end product.

PMID- 24910513
TI  - The Effect of Spatial and Nonspatial Contextual Information on Visual Object
      Memory.
AB  - Recent research has found visual object memory can be stored as part of a larger
      scene representation rather than independently of scene context. The present
      study examined how spatial and nonspatial contextual information modulate visual
      object memory. Two experiments tested participants' visual memory by using a
      change detection task in which a target object's orientation was either the same
      as it appeared during initial viewing or changed. In addition, we examined the
      effect of spatial and nonspatial contextual manipulations on change detection
      performance. The results revealed that visual object representations can be
      maintained reliably after viewing arrays of objects. Moreover, change detection
      performance was significantly higher when either spatial or nonspatial contextual
      information remained the same in the test image. We concluded that while
      processing complex visual stimuli such as object arrays, visual object memory can
      be stored as part of a comprehensive scene representation, and both spatial and
      nonspatial contextual changes modulate visual memory retrieval and comparison.

PMID- 24910514
TI  - Encoding the target or the plausible preview word? The nature of the plausibility
      preview benefit in reading Chinese.
AB  - Previous studies have shown that a plausible preview word can facilitate the
      processing of a target word as compared to an implausible preview word (a
      plausibility preview benefit effect) when reading Chinese (Yang, Wang, Tong, &
      Rayner, 2012; Yang, 2013). Regarding the nature of this effect, it is possible
      that readers processed the meaning of the plausible preview word and did not
      actually encode the target word (given that the parafoveal preview word lies
      close to the fovea). The current experiment examined this possibility with three
      conditions wherein readers received a preview of a target word that was either
      (1) identical to the target word (identical preview), (2) a plausible
      continuation of the pre-target text, but the post-target text in the sentence was
      incompatible with it (initially plausible preview), or (3) not a plausible
      continuation of the pre-target text, nor compatible with the post-target text
      (implausible preview). Gaze durations on target words were longer in the
      initially plausible condition than the identical condition. Overall, the results
      showed a typical preview benefit, but also implied that readers did not encode
      the initially plausible preview. Also, a plausibility preview benefit was
      replicated: gaze durations were longer with implausible previews than the
      initially plausible ones. Furthermore, late eye movement measures did not reveal
      differences between the initially plausible and the implausible preview
      conditions, which argues against the possibility of misreading the plausible
      preview word as the target word. In sum, these results suggest that a plausible
      preview word provides benefit in processing the target word as compared to an
      implausible preview word, and this benefit is only present in early but not late
      eye movement measures.

PMID- 24910516
TI  - Energy storage inherent in large tidal turbine farms.
AB  - While wind farms have no inherent storage to supply power in calm conditions,
      this paper demonstrates that large tidal turbine farms in channels have short
      term energy storage. This storage lies in the inertia of the oscillating flow and
      can be used to exceed the previously published upper limit for power production
      by currents in a tidal channel, while simultaneously maintaining stronger
      currents. Inertial storage exploits the ability of large farms to manipulate the
      phase of the oscillating currents by varying the farm's drag coefficient. This
      work shows that by optimizing how a large farm's drag coefficient varies during
      the tidal cycle it is possible to have some flexibility about when power is
      produced. This flexibility can be used in many ways, e.g. producing more power,
      or to better meet short predictable peaks in demand. This flexibility also allows
      trading total power production off against meeting peak demand, or mitigating the
      flow speed reduction owing to power extraction. The effectiveness of inertial
      storage is governed by the frictional time scale relative to either the duration
      of a half tidal cycle or the duration of a peak in power demand, thus has greater
      benefits in larger channels.

PMID- 24910515
TI  - Word frequency in fast priming: Evidence for immediate cognitive control of eye
      movements during reading.
AB  - Numerous studies have demonstrated effects of word frequency on eye movements
      during reading, but the precise timing of this influence has remained unclear.
      The fast priming paradigm (Sereno & Rayner, 1992) was previously used to study
      influences of related versus unrelated primes on the target word. Here, we used
      this procedure to investigate whether the frequency of the prime word has a
      direct influence on eye movements during reading when the prime-target relation
      is not manipulated. We found that with average prime intervals of 32 ms readers
      made longer single fixation durations on the target word in the low than in the
      high frequency prime condition. Distributional analyses demonstrated that the
      effect of prime frequency on single fixation durations occurred very early,
      supporting theories of immediate cognitive control of eye movements. Finding
      prime frequency effects only 207 ms after visibility of the prime and for prime
      durations of 32 ms yields new time constraints for cognitive processes
      controlling eye movements during reading. Our variant of the fast priming
      paradigm provides a new approach to test early influences of word processing on
      eye movement control during reading.

PMID- 24910517
TI  - A century of variation in the dependence of Greenland iceberg calving on ice
      sheet surface mass balance and regional climate change.
AB  - Iceberg calving is a major component of the total mass balance of the Greenland
      ice sheet (GrIS). A century-long record of Greenland icebergs comes from the
      International Ice Patrol's record of icebergs (I48N) passing latitude 48 degrees 
      N, off Newfoundland. I48N exhibits strong interannual variability, with a
      significant increase in amplitude over recent decades. In this study, we show,
      through a combination of nonlinear system identification and coupled ocean
      iceberg modelling, that I48N's variability is predominantly caused by fluctuation
      in GrIS calving discharge rather than open ocean iceberg melting. We also
      demonstrate that the episodic variation in iceberg discharge is strongly linked
      to a nonlinear combination of recent changes in the surface mass balance (SMB) of
      the GrIS and regional atmospheric and oceanic climate variability, on the scale
      of the previous 1-3 years, with the dominant causal mechanism shifting between
      glaciological (SMB) and climatic (ocean temperature) over time. We suggest that
      this is a change in whether glacial run-off or under-ice melting is dominant,
      respectively. We also suggest that GrIS calving discharge is episodic on at least
      a regional scale and has recently been increasing significantly, largely as a
      result of west Greenland sources.

PMID- 24910518
TI  - A frequency averaging framework for the solution of complex dynamic systems.
AB  - A frequency averaging framework is proposed for the solution of complex linear
      dynamic systems. It is remarkable that, while the mid-frequency region is usually
      very challenging, a smooth transition from low- through mid- and high-frequency
      ranges is possible and all ranges can now be considered in a single framework. An
      interpretation of the frequency averaging in the time domain is presented and it
      is explained that the average may be evaluated very efficiently in terms of
      system solutions.

PMID- 24910519
TI  - Convolutionless Nakajima-Zwanzig equations for stochastic analysis in nonlinear
      dynamical systems.
AB  - Determining the statistical properties of stochastic nonlinear systems is of
      major interest across many disciplines. Currently, there are no general efficient
      methods to deal with this challenging problem that involves high dimensionality,
      low regularity and random frequencies. We propose a framework for stochastic
      analysis in nonlinear dynamical systems based on goal-oriented probability
      density function (PDF) methods. The key idea stems from techniques of
      irreversible statistical mechanics, and it relies on deriving evolution equations
      for the PDF of quantities of interest, e.g. functionals of the solution to
      systems of stochastic ordinary and partial differential equations. Such
      quantities could be low-dimensional objects in infinite dimensional phase spaces.
      We develop the goal-oriented PDF method in the context of the time
      convolutionless Nakajima-Zwanzig-Mori formalism. We address the question of
      approximation of reduced-order density equations by multi-level coarse graining,
      perturbation series and operator cumulant resummation. Numerical examples are
      presented for stochastic resonance and stochastic advection-reaction problems.

PMID- 24910520
TI  - How could the Viking Sun compass be used with sunstones before and after sunset?
      Twilight board as a new interpretation of the Uunartoq artefact fragment.
AB  - Vikings routinely crossed the North Atlantic without a magnetic compass and left
      their mark on lands as far away as Greenland, Newfoundland and Baffin Island.
      Based on an eleventh-century dial fragment artefact, found at Uunartoq in
      Greenland, it is widely accepted that they sailed along chosen latitudes using
      primitive Sun compasses. Such instruments were tested on sea and proved to be
      efficient hand-held navigation tools, but the dimensions and incisions of the
      Uunartoq find are far from optimal in this role. On the basis of the sagas
      mentioning sunstones, incompatible hypotheses were formed for Viking solar
      navigation procedures and primitive skylight polarimetry with dichroic or
      birefringent crystals. We describe here a previously unconceived method of
      navigation based on the Uunartoq artefact functioning as a 'twilight board',
      which is a combination of a horizon board and a Sun compass optimized for use
      when the Sun is close to the horizon. We deduced an appropriate solar navigation
      procedure using a twilight board, a shadow-stick and birefringent crystals, which
      bring together earlier suggested methods in harmony and provide a true skylight
      compass function. This could have allowed Vikings to navigate around the clock,
      to use the artefact dial as a Sun compass during long parts of the day and to use
      skylight polarization patterns in the twilight period. In field tests, we found
      that true north could be appointed with such a medieval skylight compass with an
      error of about +/-4 degrees  when the artificially occluded Sun had elevation
      angles between +10 degrees  and -8 degrees  relative to the horizon. Our
      interpretation allows us to assign exact dates to the gnomonic lines on the
      artefact and outlines the schedule of the merchant ships that sustained the
      Viking colony in Greenland a millennium ago.

PMID- 24910521
TI  - Deformation field heterogeneity in punch indentation.
AB  - Plastic heterogeneity in indentation is fundamental for understanding mechanics
      of hardness testing and impression-based deformation processing methods. The
      heterogeneous deformation underlying plane-strain indentation was investigated in
      plastic loading of copper by a flat punch. Deformation parameters were measured,
      in situ, by tracking the motion of asperities in high-speed optical imaging.
      These measurements were coupled with multi-scale analyses of strength,
      microstructure and crystallographic texture in the vicinity of the indentation.
      Self-consistency is demonstrated in description of the deformation field using
      the in situ mechanics-based measurements and post-mortem materials
      characterization. Salient features of the punch indentation process elucidated
      include, among others, the presence of a dead-metal zone underneath the indenter,
      regions of intense strain rate (e.g. slip lines) and extent of the plastic flow
      field. Perhaps more intriguing are the transitions between shear-type and
      compression-type deformation modes over the indentation region that were
      quantified by the high-resolution crystallographic texture measurements. The
      evolution of the field concomitant to the progress of indentation is discussed
      and primary differences between the mechanics of indentation for a rigid
      perfectly plastic material and a strain-hardening material are described.

PMID- 24910522
TI  - A reduced-order model from high-dimensional frictional hysteresis.
AB  - Hysteresis in material behaviour includes both signum nonlinearities as well as
      high dimensionality. Available models for component-level hysteretic behaviour
      are empirical. Here, we derive a low-order model for rate-independent hysteresis
      from a high-dimensional massless frictional system. The original system, being
      given in terms of signs of velocities, is first solved incrementally using a
      linear complementarity problem formulation. From this numerical solution, to
      develop a reduced-order model, basis vectors are chosen using the singular value
      decomposition. The slip direction in generalized coordinates is identified as the
      minimizer of a dissipation-related function. That function includes terms for
      frictional dissipation through signum nonlinearities at many friction sites.
      Luckily, it allows a convenient analytical approximation. Upon solution of the
      approximated minimization problem, the slip direction is found. A final evolution
      equation for a few states is then obtained that gives a good match with the full
      solution. The model obtained here may lead to new insights into hysteresis as
      well as better empirical modelling thereof.

PMID- 24910523
TI  - Generalization of the Schwarz-Christoffel mapping to multiply connected polygonal
      domains.
AB  - A generalization of the Schwarz-Christoffel mapping to multiply connected
      polygonal domains is obtained by making a combined use of two preimage domains,
      namely, a rectilinear slit domain and a bounded circular domain. The conformal
      mapping from the circular domain to the polygonal region is written as an
      indefinite integral whose integrand consists of a product of powers of the
      Schottky-Klein prime functions, which is the same irrespective of the preimage
      slit domain, and a prefactor function that depends on the choice of the
      rectilinear slit domain. A detailed derivation of the mapping formula is given
      for the case where the preimage slit domain is the upper half-plane with radial
      slits. Representation formulae for other canonical slit domains are also obtained
      but they are more cumbersome in that the prefactor function contains arbitrary
      parameters in the interior of the circular domain.

PMID- 24910524
TI  - Propagation in waveguides with varying cross section and curvature: a new light
      on the role of supplementary modes in multi-modal methods.
AB  - We present an efficient multi-modal method to describe the acoustic propagation
      in waveguides with varying curvature and cross section. A key feature is the use
      of a flexible geometrical transformation to a virtual space in which the
      waveguide is straight and has unitary cross section. In this new space, the
      pressure field has to satisfy a modified wave equation and associated modified
      boundary conditions. These boundary conditions are in general not satisfied by
      the Neumann modes, used for the series representation of the field. Following
      previous work, an improved modal method (MM) is presented, by means of the use of
      two supplementary modes. Resulting increased convergences are exemplified by
      comparison with the classical MM. Next, the following question is addressed: when
      the boundary conditions are verified by the Neumann modes, does the use of
      supplementary modes improve or degrade the convergence of the computed solution?
      Surprisingly, although the supplementary modes degrade the behaviour of the
      solution at the walls, they improve the convergence of the wavefield and of the
      scattering coefficients. This sheds a new light on the role of the supplementary
      modes and opens the way for their use in a wide range of scattering problems.

PMID- 24910525
TI  - Flutter in a quasi-one-dimensional model of a collapsible channel.
AB  - The effects of wall inertia on instabilities in a collapsible channel with a long
      finite-length flexible wall containing a high Reynolds number flow of
      incompressible fluid are studied. Using the ideas of interactive boundary layer
      theory, the system is described by a one-dimensional model that couples inviscid
      flow outside the boundary layers formed on the channel walls with the deformation
      of the flexible wall. The observed instability is a form of flutter, which is
      superposed on the behaviour of the system when the wall mass is neglected. We
      show that the flutter has a positive growth rate because the fluid loading acts
      as a negative damping in the system. We discuss these findings in relation to
      other work on self-excited oscillations in collapsible channels.

PMID- 24910526
TI  - Causal dissipation and shock profiles in the relativistic fluid dynamics of pure
      radiation.
AB  - CURRENT THEORIES OF DISSIPATION IN THE RELATIVISTIC REGIME SUFFER FROM ONE OF TWO
      DEFICITS: either their dissipation is not causal or no profiles for strong shock
      waves exist. This paper proposes a relativistic Navier-Stokes-Fourier-type
      viscosity and heat conduction tensor such that the resulting second-order system
      of partial differential equations for the fluid dynamics of pure radiation is
      symmetric hyperbolic. This system has causal dissipation as well as the property
      that all shock waves of arbitrary strength have smooth profiles. Entropy
      production is positive both on gradients near those of solutions to the
      dissipation-free equations and on gradients of shock profiles. This shows that
      the new dissipation stress tensor complies to leading order with the principles
      of thermodynamics. Whether higher order modifications of the ansatz are required
      to obtain full compatibility with the second law far from the zero-dissipation
      equilibrium is left to further investigations. The system has exactly three a
      priori free parameters chi,eta,zeta, corresponding physically to heat
      conductivity, shear viscosity and bulk viscosity. If the bulk viscosity is zero
      (as is stated in the literature) and the total stress-energy tensor is trace
      free, the entire viscosity and heat conduction tensor is determined to within a
      constant factor.

PMID- 24910527
TI  - On nonlinear viscoelastic deformations: a reappraisal of Fung's quasi-linear
      viscoelastic model.
AB  - This paper offers a reappraisal of Fung's model for quasi-linear viscoelasticity.
      It is shown that a number of negative features exhibited in other works, commonly
      attributed to the Fung approach, are merely a consequence of the way it has been
      applied. The approach outlined herein is shown to yield improved behaviour and
      offers a straightforward scheme for solving a wide range of models. Results from
      the new model are contrasted with those in the literature for the case of
      uniaxial elongation of a bar: for an imposed stretch of an incompressible bar and
      for an imposed load. In the latter case, a numerical solution to a Volterra
      integral equation is required to obtain the results. This is achieved by a high
      order discretization scheme. Finally, the stretch of a compressible viscoelastic
      bar is determined for two distinct materials: Horgan-Murphy and Gent.

PMID- 24910528
TI  - Supra-molecular assembly of aromatic proton sponges to direct the crystallization
      of extra-large-pore zeotypes.
AB  - The combination of different experimental techniques, such as solid 13C and 1H
      magic-angle spinning NMR spectroscopy, fluorescence spectroscopy and powder X-ray
      diffraction, together with theoretical calculations allows the determination of
      the unique structure directing the role of the bulky aromatic proton sponge 1,8
      bis(dimethylamino)naphthalene (DMAN) towards the extra-large-pore ITQ-51 zeolite
      through supra-molecular assemblies of those organic molecules.

PMID- 24910529
TI  - Cumulative distribution function solutions of advection-reaction equations with
      uncertain parameters.
AB  - We derive deterministic cumulative distribution function (CDF) equations that
      govern the evolution of CDFs of state variables whose dynamics are described by
      the first-order hyperbolic conservation laws with uncertain coefficients that
      parametrize the advective flux and reactive terms. The CDF equations are
      subjected to uniquely specified boundary conditions in the phase space, thus
      obviating one of the major challenges encountered by more commonly used
      probability density function equations. The computational burden of solving CDF
      equations is insensitive to the magnitude of the correlation lengths of random
      input parameters. This is in contrast to both Monte Carlo simulations (MCSs) and
      direct numerical algorithms, whose computational cost increases as correlation
      lengths of the input parameters decrease. The CDF equations are, however, not
      exact because they require a closure approximation. To verify the accuracy and
      robustness of the large-eddy-diffusivity closure, we conduct a set of numerical
      experiments which compare the CDFs computed with the CDF equations with those
      obtained via MCSs. This comparison demonstrates that the CDF equations remain
      accurate over a wide range of statistical properties of the two input parameters,
      such as their correlation lengths and variance of the coefficient that
      parametrizes the advective flux.

PMID- 24910530
TI  - Mast cell-nerve cell interaction at acupoint: modeling mechanotransduction
      pathway induced by acupuncture.
AB  - Mast cells are found abundant at sites of acupoints. Nerve cells share
      perivascular localization with mast cells. Acupuncture (mechanical stimuli) can
      activate mast cells to release adenosine triphosphate (ATP) which can activate
      nerve cells and modulates pain-processing pathways in response to acupuncture. In
      this paper, a mathematical model was constructed for describing intracellular
      Ca(2+) signal and ATP release in a coupled mast cell and nerve cell system
      induced by mechanical stimuli. The results showed mechanical stimuli lead to a
      intracellular Ca(2+) rise in the mast cell and ATP release, ATP diffuses in the
      extracellular space (ECS) and activates the nearby nerve cells, then induces
      electrical current in the nerve cell which spreads in the neural network. This
      study may facilitate our understanding of the mechanotransduction process induced
      by acupuncture and provide a methodology for quantitatively analyzing acupuncture
      treatment. 

PMID- 24910531
TI  - Macrophage polarization in inflammatory diseases.
AB  - Diversity and plasticity are two hallmarks of macrophages. M1 macrophages
      (classically activated macrophages) are pro-inflammatory and have a central role
      in host defense against infection, while M2 macrophages (alternatively activated
      macrophages) are associated with responses to anti-inflammatory reactions and
      tissue remodeling, and they represent two terminals of the full spectrum of
      macrophage activation. Transformation of different phenotypes of macrophages
      regulates the initiation, development, and cessation of inflammatory diseases.
      Here we reviewed the characters and functions of macrophage polarization in
      infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that
      targeting macrophage polarization and skewing their phenotype to adapt to the
      microenvironment might hold great promise for the treatment of inflammatory
      diseases. 

PMID- 24910532
TI  - Detailed localization of augmented angiotensinogen mRNA and protein in proximal
      tubule segments of diabetic kidneys in rats and humans.
AB  - In the intrarenal renin-angiotensin system, angiotensinogen levels are well known
      to be increased in diabetes, and these enhanced intrarenal angiotensinogen levels
      may initiate the development and accelerate the progression of diabetic
      nephropathy. However, the specific localization of the augmented angiotensinogen
      in proximal tubule segments in diabetes is still unknown. We investigated the
      detailed localization of angiotensinogen in 3 proximal tubule segments in the
      diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and the control Long
      Evans Tokushima Otsuka (LETO) rats. We also prepared OLETF rats treated with
      angiotensin II type 1 receptor blocker, olmesartan or with a combination of
      vasodilator agents. Moreover, biopsied samples of human kidney cortex were used
      to confirm the results of animal studies. We examined the co-localization of
      angiotensinogen with segment-specific markers by double staining using
      fluorescence in situ hybridization and/or immunofluorescence. Angiotensinogen
      mRNA expression was barely detectable in segment 1. In segment 3, the area of
      angiotensinogen mRNA expression was augmented in the OLETF rats compared with the
      LETO rats. Angiotensinogen protein expression areas in segments 1 and 3 were also
      increased in the OLETF rats compared with the LETO rats. Chronic treatment with
      olmesartan ameliorated these areas of augmented angiotensinogen expression.
      Biopsied human kidney samples showed similar results. These data suggest that the
      augmented angiotensinogen mRNA levels in segment 3 and angiotensinogen protein
      levels in segments 1 and 3 may contribute to the progression of diabetic
      nephropathy. 

PMID- 24910533
TI  - DLG5 in cell polarity maintenance and cancer development.
AB  - Failure in establishment and maintenance of epithelial cell polarity contributes
      to tumorigenesis. Loss of expression and function of cell polarity proteins is
      directly related to epithelial cell polarity maintenance. The polarity protein
      discs large homolog 5 (DLG5) belongs to a family of molecular scaffolding
      proteins called Membrane Associated Guanylate Kinases (MAGUKs). As the other
      family members, DLG5 contains the multi-PDZ, SH3 and GUK domains. DLG5 has
      evolved in the same manner as DLG1 and ZO1, two well-studied MAGUKs proteins.
      Just like DLG1 and ZO1, DLG5 plays a role in cell migration, cell adhesion,
      precursor cell division, cell proliferation, epithelial cell polarity
      maintenance, and transmission of extracellular signals to the membrane and
      cytoskeleton. Since the roles of DLG5 in inflammatory bowel disease (IBD) and
      Crohn's disease (CD) have been reviewed, here, our review focuses on the roles of
      DLG5 in epithelial cell polarity maintenance and cancer development. 

PMID- 24910536
TI  - Radiation pneumonitis and pulmonary function with lung dose-volume constraints in
      breast cancer irradiation.
AB  - PURPOSE: We studied symptomatic radiation pneumonitis (RP) and changes in
      pulmonary function tests (PFTs) after loco-regional radiotherapy (LRRT) with V20
      lung constraints in breast cancer (BC). PATIENTS AND METHODS: Sixty-four women
      underwent PFTs before and 5 months after 3D planned LRRT for BC. The incidentally
      irradiated ipsilateral lung V20 was minimised to <30%. Patients were monitored
      for symptoms of RP 1, 4 and 7 months after radiotherapy (RT) and data on
      covariates were collected prospectively. The outcome was compared with previous
      treatment series. RESULTS: Pneumonitis was less frequent with the applied
      constraint, that is, four mild and one moderate case, than in our previous report
      (p < 0.001). In multivariate analyses, neither dosimetric data nor covariates
      appeared to influence mean changes in vital capacity [-0.11L, standard error of
      the mean (SEM) 0.03] or diffusing capacity of the lung for carbon monoxide (DLCO)
      (-0.20 mmol/kPa/min, SEM 0.01), except for pre-RT chemotherapy, which diminished
      the change in DLCO 5 months post-RT. CONCLUSIONS: The used constraint and 3D
      planning lowered the rate of RP and short-term changes in PFTs compared with our
      previous treatment series. Pre-RT chemotherapy affects DLCO baseline levels.
      Rates of side effects should be continuously studied when new target definitions
      or therapies are introduced in LRRT of BC.

PMID- 24910537
TI  - Acute abdominal compartment syndrome as a complication of Holmium laser
      enucleation of the prostate: a case report.
AB  - BACKGROUND: In 1996, Holmium laser enucleation of the prostate was introduced and
      has been shown to be safe and highly effective. CASE PRESENTATION: We report a
      case of a rare complication that resulted in intra-abdominal compartment syndrome
      with prolonged intubation and intensive care, involving an 74-year-old male after
      holmium laser enucleation of prostate, with a massive irrigant fluid leakage into
      the retroperitoneal space. The elevated abdominal pressure was reduced by forced
      diuresis. The tracheal tube was removed 18 hours after the patient's transfer to
      the ICU. The patient was discharged to home one week after the operation.
      CONCLUSION: In rare cases when no obvious ruptures of the prostate capsule or the
      bladder occur during laser enucleation of prostate, knowledge regarding possible
      emersion of massive amounts of irrigant fluid into the retroperitoneal space
      leading to intra-abdominal compartment syndrome aids in the diagnosis and
      subsequent successful therapy of intra-abdominal hypertension.

PMID- 24910535
TI  - BRCA1 and estrogen/estrogen receptor in breast cancer: where they interact?
AB  - BRCA1 mainly acts as a tumor suppressor and BRCA1 mutation correlates with
      increased cancer risk. Although it is well recognized that BRCA1 related
      tumorigenesis is mainly caused by the increased DNA damage and decreased genome
      stability, it is not clear that why BRCA1 related patients have higher risk for
      cancer development mainly in estrogen responsive tissues such as breast and
      ovary. Recent studies suggested that BRCA1 and E-ER (estrogen and estrogen
      receptor) signaling synergistically regulate the mammary epithelial cell
      proliferation and differentiation. In this current presentation, we reviewed the
      correlation between mammary gland epithelial cell transformation and the status
      of BRCA1 and ER. Then the mechanisms of BRCA1 and E-ER interaction at both gene
      transcription level and protein-protein interaction level are discussed.
      Furthermore, the tumorigenic mechanisms are discussed by focusing on the
      synergistic effect of BRCA1 and E-ER on cell metabolism, ROS management, and
      antioxidant activity in mammary gland epithelial cells. Also, the possibility of
      cell de-differentiation promoted by coordinated effect between BRCA1 mutation and
      E-ER signal is explored. Together, the currently available evidences suggest that
      BRCA1 mutation and E-ER signal together, contribute to breast tumorigenesis by
      providing the metabolic support for cancer cell growth and even may directly be
      involved in promoting the de-differentiation of cancer-prone epithelial cells. 

PMID- 24910534
TI  - Quorum quenching mediated approaches for control of membrane biofouling.
AB  - Membrane biofouling is widely acknowledged as the most frequent adverse event in
      wastewater treatment systems resulting in significant loss of treatment
      efficiency and economy. Different strategies including physical cleaning and use
      of antimicrobial chemicals or antibiotics have been tried for reducing membrane
      biofouling. Such traditional practices are aimed to eradicate biofilms or kill
      the bacteria involved, but the greater efficacy in membrane performance would be
      achieved by inhibiting biofouling without interfering with bacterial growth. As a
      result, the search for environmental friendly non-antibiotic antifouling
      strategies has received much greater attention among scientific community. The
      use of quorum quenching natural compounds and enzymes will be a potential
      approach for control of membrane biofouling. This approach has previously proven
      useful in diseases and membrane biofouling control by triggering the expression
      of desired phenotypes. In view of this, the present review is provided to give
      the updated information on quorum quenching compounds and elucidate the
      significance of quorum sensing inhibition in control of membrane biofouling. 

PMID- 24910539
TI  - A pilot study to assess feasibility of value based pricing in Cyprus through
      pharmacoeconomic modelling and assessment of its operational framework: sorafenib
      for second line renal cell cancer.
AB  - BACKGROUND: The continuing increase of pharmaceutical expenditure calls for new
      approaches to pricing and reimbursement of pharmaceuticals. Value based pricing
      of pharmaceuticals is emerging as a useful tool and possess theoretical
      attributes to help health system cope with rising pharmaceutical expenditure.
      AIM: To assess the feasibility of introducing a value-based pricing scheme of
      pharmaceuticals in Cyprus and explore the integrative framework. METHODS: A
      probabilistic Markov chain Monte Carlo model was created to simulate progression
      of advanced renal cell cancer for comparison of sorafenib to standard best
      supportive care. Literature review was performed and efficacy data were
      transferred from a published landmark trial, while official pricelists and
      clinical guidelines from Cyprus Ministry of Health were utilised for cost
      calculation. Based on proposed willingness to pay threshold the maximum price of
      sorafenib for the indication of second line renal cell cancer was assessed.
      RESULTS: Sorafenib value based price was found to be significantly lower compared
      to its current reference price. CONCLUSION: Feasibility of Value Based Pricing is
      documented and pharmacoeconomic modelling can lead to robust results. Integration
      of value and affordability in the price are its main advantages which have to be
      weighed against lack of documentation for several theoretical parameters that
      influence outcome. Smaller countries such as Cyprus may experience adversities in
      establishing and sustaining essential structures for this scheme.

PMID- 24910538
TI  - Effect of Ku70 expression on radiosensitivity in renal carcinoma 786-O cells.
AB  - BACKGROUND: Radiotherapy plays an important role in cancer therapy. However, the
      radioresistance of some human cancers, particularly renal carcinoma, often
      results in radiotherapy failure. The Ku protein is essential for the repair of a
      majority of DNA double-strand breaks in mammalian cells, but effect of Ku70
      expression on radiosensitivity in renal carcinoma is unclear. Here, we
      investigate the impact of Ku70 on radiosensitivity in renal carcinoma cells
      through regulating the expression of Ku70. METHODS: The stable overexpression of
      Ku70 or suppression of Ku70 in renal carcinoma cell line (786-O) was generated by
      retrovirus-mediated Ku70 cDNA or shRNA targeting Ku70. Ku70 expression was
      determined by RT-PCR and Western blot analysis, the apoptosis of the stable cells
      was assayed with flow cytometry and TUNEL assay and the effect of radiation on
      the livability of stable cells was assessed by MTT assay. RESULTS: Up-regulation
      of Ku70 expression of 786-O cells could inhibit cell apoptosis and reduce
      susceptibility to radiation. On the contrary, 786-O cells with suppression of
      Ku70 expression could induce cell apoptosis and significantly enhance the
      sensitivity to radiation. CONCLUSIONS: These findings indicated that Ku70 might
      play an important role in radioresistance of renal carcinoma, and inhibition of
      Ku70 can increase the radiosensitivity of 786-O cells by enhancing apoptosis,
      suggesting down-regulation of Ku70 expression combined with radiotherapy will be
      a potential strategy for renal cell carcinoma therapy.

PMID- 24910540
TI  - Why equal treatment is not always equitable: the impact of existing ethnic health
      inequalities in cost-effectiveness modeling.
AB  - BACKGROUND: A critical first step toward incorporating equity into cost
      effectiveness analyses is to appropriately model interventions by population
      subgroups. In this paper we use a standardized treatment intervention to examine
      the impact of using ethnic-specific (Maori and non-Maori) data in cost-utility
      analyses for three cancers. METHODS: We estimate gains in health-adjusted life
      years (HALYs) for a simple intervention (20% reduction in excess cancer
      mortality) for lung, female breast, and colon cancers, using Markov modeling.
      Base models include ethnic-specific cancer incidence with other parameters either
      turned off or set to non-Maori levels for both groups. Subsequent models add
      ethnic-specific cancer survival, morbidity, and life expectancy. Costs include
      intervention and downstream health system costs. RESULTS: For the three cancers,
      including existing inequalities in background parameters (population mortality
      and comorbidities) for Maori attributes less value to a year of life saved
      compared to non-Maori and lowers the relative health gains for Maori. In
      contrast, ethnic inequalities in cancer parameters have less predictable effects.
      Despite Maori having higher excess mortality from all three cancers, modeled
      health gains for Maori were less from the lung cancer intervention than for non
      Maori but higher for the breast and colon interventions. CONCLUSIONS: Cost
      effectiveness modeling is a useful tool in the prioritization of health services.
      But there are important (and sometimes counterintuitive) implications of
      including ethnic-specific background and disease parameters. In order to avoid
      perpetuating existing ethnic inequalities in health, such analyses should be
      undertaken with care.

PMID- 24910541
TI  - State Responses to Alcohol Use and Pregnancy: Findings From the Alcohol Policy
      Information System (APIS).
AB  - This article describes U.S. state policies related to alcohol use during
      pregnancy, using data from the National Institute on Alcohol Abuse and Alcoholism
      (NIAAA) Alcohol Policy Information System (APIS). Specifically, this study
      examines trends in policies enacted by states over time and types of policies
      enacted across states in the U.S., with a focus on whether laws were supportive
      or punitive toward women. Findings revealed substantial variability in
      characteristics of policies (19 primarily supportive, 12 primarily punitive, 12
      with a mixed approach, and 8 with no policies). Findings underscore the need to
      examine possible consequences of policies, especially of punitive policies and
      "mixed" approaches.

PMID- 24910542
TI  - Improved Coarse-Grained Modeling of Cholesterol-Containing Lipid Bilayers.
AB  - Cholesterol trafficking, which is an essential function in mammalian cells, is
      intimately connected to molecular-scale interactions through cholesterol
      modulation of membrane structure and dynamics and interaction with membrane
      receptors. Since these effects of cholesterol occur on micro- to millisecond
      timescales, it is essential to develop accurate coarse-grained simulation models
      that can reach these timescales. Cholesterol has been shown experimentally to
      thicken the membrane and increase phospholipid tail order between 0-40%
      cholesterol, above which these effects plateau or slightly decrease. Here, we
      showed that the published MARTINI coarse-grained force-field for phospholipid
      (POPC) and cholesterol fails to capture these effects. Using reference atomistic
      simulations, we systematically modified POPC and cholesterol bonded parameters in
      MARTINI to improve its performance. We showed that the corrections to pseudo-bond
      angles between glycerol and the lipid tails and around the oleoyl double bond
      particle (the "angle-corrected model") slightly improves the agreement of MARTINI
      with experimentally measured thermal, elastic, and dynamic properties of POPC
      membranes. The angle-corrected model improves prediction of the thickening and
      ordering effects up to 40% cholesterol but overestimates these effects at higher
      cholesterol concentration. In accordance with prior work that showed the
      cholesterol rough face methyl groups are important for limiting cholesterol self
      association, we revised the coarse-grained representation of these methyl groups
      to better match cholesterol-cholesterol radial distribution functions from
      atomistic simulations. In addition, by using a finer-grained representation of
      the branched cholesterol tail than MARTINI, we improved predictions of lipid tail
      order and bilayer thickness across a wide range of concentrations. Finally,
      transferability testing shows that a model incorporating our revised parameters
      into DOPC outperforms other CG models in a DOPC/cholesterol simulation series,
      which further argues for its efficacy and generalizability. These results argue
      for the importance of systematic optimization for coarse-graining biologically
      important molecules like cholesterol with complicated molecular structure.

PMID- 24910543
TI  - Effect of an herbal/botanical supplement on strength, balance, and muscle
      function following 12-weeks of resistance training: a placebo controlled study.
AB  - BACKGROUND: StemSport (SS; StemTech International, Inc. San Clemente, CA)
      contains a proprietary blend of the botanical Aphanizomenon flos-aquae and
      several herbal antioxidant and anti-inflammatory substances. SS has been
      purported to accelerate tissue repair and restore muscle function following
      resistance exercise. Here, we examine the effects of SS supplementation on
      strength adaptations resulting from a 12-week resistance training program in
      healthy young adults. METHODS: Twenty-four young adults (16 males, 8 females,
      mean age = 20.5 +/- 1.9 years, mass = 70.9 +/- 11.9 kg, stature = 176.6 +/- 9.9
      cm) completed the twelve week training program. The study design was a double
      blind, placebo controlled parallel group trial. Subjects either received placebo
      or StemSport supplement (SS; mg/day) during the training. 1-RM bench press, 1-RM
      leg press, vertical jump height, balance (star excursion and center of mass
      excursion), isokinetic strength (elbow and knee flexion/extension) and perception
      of recovery were measured at baseline and following the 12-week training
      intervention. RESULTS: Resistance training increased 1-RM strength (p < 0.008),
      vertical jump height (p < 0.03), and isokinetic strength (p < 0.05) in both SS
      and placebo groups. No significant group-by-time interactions were observed (all
      p-values >0.10). CONCLUSIONS: These data suggest that compared to placebo, the SS
      herbal/botanical supplement did not enhance training induced adaptations to
      strength, balance, and muscle function above strength training alone.

PMID- 24910544
TI  - Do glucose containing beverages play a role in thermoregulation, thermal
      sensation, and mood state?
AB  - INTRODUCTION: Dehydration limits the appropriate delivery of oxygen and
      substrates to the working muscle. Further, the brain's ability to function may
      also be compromised whereby thermal sensation and mood state may be altered.
      PURPOSE: The purpose of the present investigation was to compare the
      thermoregulatory, perceptual, and negative mood state profile in glucose (GLU)
      vs. non-glucose beverage (NON-GLU) condition. METHODS: Ten healthy men
      volunteered and were counterbalanced either a GLU or NON-GLU containing beverage
      on separate mornings. In each condition, they were exposed to 37 degrees C, 50%
      relative humidity (RH) for baseline, exercise, rehydration, and recovery periods.
      The exercise period elicited the desired level of dehydration (mean of 2.6 +/-
      0.3% body weight losses). Upon completion of the protracted exercise,
      participants were administered either a GLU or NON-GLU containing electrolyte
      based sports drink ad libitum for 30 min, followed by a recovery period of 15 min
      in 37 degrees C, 50% RH. Rectal (Tre) and mean skin temperatures (Tsk) were
      continuously monitored. Gagge (TS) and heated thermal sensation (HTS), profile of
      mood state (POMS) were measure at the end of each period. RESULTS: During
      recovery after rehydration, Tre was not significantly different between
      conditions (GLU vs. NON-GLU) (37.4 +/- 0.8 vs. 37.0 +/- 1.2 degrees C); Tsk was
      also not affected by rehydration in both conditions (36.0 +/- 0.5 vs. 36.0 +/-
      0.6 degrees C) and, TS and HTS did not differ between conditions (0.9 +/- 1.3
      vs.1.3 +/- 0.7) and (1.0 +/- 0.8 vs.0.8 +/- 0.3). Total mood disturbance (TMD)
      score for the POMS was utilized for overall negative mood state and demonstrated
      a main effect for time (p < 0.05). TMD during recovery was decreased compared to
      before hydration in both conditions. CONCLUSION: The non-glucose containing
      beverage maintained plasma volume and was effective at maintaining body
      temperature homeostasis in a similar fashion compared to the glucose containing
      beverage. Furthermore, negative mood state was not different between the two
      conditions. The non-glucose beverages can serve a valuable role in the exercise
      environment depending upon the sport, the ambient temperature, the individual,
      duration of the exercise, the age and training states of the individual.

PMID- 24910545
TI  - Ensuring patient access to sleep specialty care in the evolving U.S. healthcare
      system: introducing the Welltrinsic Sleep Network: an investment of the American
      Academy of Sleep Medicine.

PMID- 24910546
TI  - Impact of CPAP on activity patterns and diet in patients with obstructive sleep
      apnea (OSA).
AB  - STUDY OBJECTIVES: Patients with severe OSA consume greater amounts of
      cholesterol, protein, and fat as well as have greater caloric expenditure.
      However, it is not known whether their activity levels or diet change after
      treatment with CPAP. To investigate this issue, serial assessments of activity
      and dietary intake were performed in the Apnea Positive Pressure Long-term
      Efficacy Study (APPLES); a 6-month randomized controlled study of CPAP vs. sham
      CPAP on neurocognitive outcomes. METHODS: Subjects were recruited into APPLES at
      5 sites through clinic encounters or public advertisement. After undergoing a
      diagnostic polysomnogram, subjects were randomized to CPAP or sham if their AHI
      was >= 10. Adherence was assessed using data cards from the devices. At the
      Tucson and Walla Walla sites, subjects were asked to complete validated activity
      and food frequency questionnaires at baseline and their 4-month visit. RESULTS:
      Activity and diet data were available at baseline and after 4 months treatment
      with CPAP or sham in up to 231 subjects (117 CPAP, 114 Sham). Mean age, AHI, BMI,
      and Epworth Sleepiness Score (ESS) for this cohort were 55 +/- 13 [SD] years, 44
      +/- 27 /h, 33 +/- 7.8 kg/m(2), and 10 +/- 4, respectively. The participants
      lacking activity and diet data were younger, had lower AHI and arousal index, and
      had better sleep efficiency (p < 0.05). The BMI was higher among women in both
      CPAP and Sham groups. However, compared to women, men had higher AHI only in the
      CPAP group (50 vs. 34). Similarly, the arousal index was higher among men in CPAP
      group. Level of adherence defined as hours of device usage per night at 4 months
      was significantly higher among men in CPAP group (4.0 +/- 2.9 vs. 2.6 +/- 2.6).
      No changes in consumption of total calories, protein, carbohydrate or fat were
      noted after 4 months. Except for a modest increase in recreational activity in
      women (268 +/- 85 vs. 170 +/- 47 calories, p < 0.05), there also were no changes
      in activity patterns. CONCLUSION: Except for a modest increase in recreational
      activity in women, OSA patients treated with CPAP do not substantially change
      their diet or physical activity habits after treatment. .

PMID- 24910547
TI  - From couch potato to gym junkie--CPAP may not be the answer.

PMID- 24910549
TI  - The impact of obstructive sleep apnea on motor skill acquisition and
      consolidation.
AB  - STUDY OBJECTIVE: Recent investigations suggest that motor skill learning is
      impaired in patients with obstructive sleep apnea (OSA) syndrome; however, it is
      not fully understood at what stages of learning this impairment occurs. The
      current study aimed to compare motor learning and memory across both daytime
      acquisition and overnight consolidation. METHODS: Twelve OSA patients and twelve
      control participants, matched for age and education, were recruited and completed
      the Karolinska Sleepiness Scale and the sequential finger-tapping task (SFTT), a
      motor skill learning task, both before and after polysomnographic recorded sleep.
      RESULTS: During the evening acquisition phase both groups showed significant and
      equitable improvement in the number of correctly typed sequences across trials.
      On retesting the following morning, the control patients showed significantly
      greater improvement overnight (15.35%) compared to OSA patients (1.78%). The post
      sleep improvement in controls, but lacking in OSA patients, was typical of a
      sleep dependent enhancement effect. The magnitude of improvement overnight for
      either group was not significantly correlated with any of the recorded sleep
      variables. CONCLUSIONS: These results suggest daytime/practice related
      acquisition of motor skill is largely intact in OSA patients; however, marked
      impairment in the consolidation phase is evident following a sleep period. This
      particular pattern of dysfunction may remain unnoticed following single-day
      learning/memory assessments.

PMID- 24910548
TI  - Effect of obstructive sleep apnea hypopnea syndrome on lipid profile: a meta
      regression analysis.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with obesity, metabolic
      syndrome, and dyslipidemia, which may be related to decrease androgen levels
      found in OSA patients. Dyslipidemia may contribute to atherosclerosis leading to
      increasing risk of heart disease. METHODS: Systematic review was conducted using
      PubMed and Cochrane library by utilizing different combinations of key words;
      sleep apnea, obstructive sleep apnea, serum lipids, dyslipidemia, cholesterol,
      total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL),
      and triglyceride (TG). Inclusion criteria were: English articles, and studies
      with adult population in 2 groups of patients (patients with OSA and without
      OSA). A total 96 studies were reviewed for inclusion, with 25 studies pooled for
      analysis. RESULTS: Sixty-four studies were pooled for analysis; since some
      studies have more than one dataset, there were 107 datasets with 18,116 patients
      pooled for meta-analysis. All studies measured serum lipids. Total cholesterol
      pooled standardized difference in means was 0.267 (p = 0.001). LDL cholesterol
      pooled standardized difference in means was 0.296 (p = 0.001). HDL cholesterol
      pooled standardized difference in means was -0.433 (p = 0.001). Triglyceride
      pooled standardized difference in means was 0.603 (p = 0.001). Meta-regression
      for age, BMI, and AHI showed that age has significant effect for TC, LDL, and
      HDL. BMI had significant effect for LDL and HDL, while AHI had significant effect
      for LDL and TG. CONCLUSION: Patients with OSA appear to have increased
      dyslipidemia (high total cholesterol, LDL, TG, and low HDL).

PMID- 24910550
TI  - Validation of the Apnea Risk Evaluation System (ARES) device against laboratory
      polysomnography in pregnant women at risk for obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVE: To assess the validity of using the Apnea Risk Evaluation System
      (ARES) Unicorder for detecting obstructive sleep apnea (OSA) in pregnant women.
      METHODS: Sixteen pregnant women, mean age (SD) = 29.8 (5.4) years, average
      gestational age (SD) = 28.6 (6.3) weeks, mean body mass index (SD) = 44.7 (6.9)
      kg/m(2) with signs and symptoms of OSA wore the ARES Unicorder during one night
      of laboratory polysomnography (PSG). PSG was scored according to AASM 2007
      criteria, and PSG AHI and RDI were compared to the ARES 1%, 3%, and 4% AHIs
      calculated with the ARES propriety software. RESULTS: Median PSG AHI and PSG RDI
      were 3.1 and 10.3 events/h of sleep, respectively. Six women had a PSG AHI >= 5
      events/h of sleep and 11 had a PSG RDI >= 5 events/h of sleep. PSG AHI and RDI
      were strongly correlated with the ARES AHI measures. When compared with
      polysomnographic diagnosis of OSA, the ARES 3% algorithm provided the best
      balance between sensitivity (1.0 for PSG AHI, 0.91 for PSG RDI) and specificity
      (0.5 for PSG AHI, 0.8 for PSG RDI) for detecting sleep disordered breathing in
      our sample. CONCLUSIONS: The ARES Unicorder demonstrated reasonable consistency
      with PSG for diagnosing OSA in this small, heterogeneous sample of obese pregnant
      women.

PMID- 24910551
TI  - Severity of obstructive sleep apnea influences the effect of genotype on response
      to anti-arrhythmic drug therapy for atrial fibrillation.
AB  - STUDY OBJECTIVES: To examine the impact of genotype on the relationship between
      obstructive sleep apnea (OSA) and anti-arrhythmic drug (AAD) efficacy in atrial
      fibrillation (AF). DESIGN: Registry based. SETTING: Clinic-based. PARTICIPANTS:
      Eighty-four individuals from Vanderbilt AF registry who had polysomnography,
      genotyping, and serial comprehensive evaluations of AF status. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Response to AADs was defined as a decrease in AF
      burden score by >= 75% or the combination of sinus rhythm on follow-up EKGs,
      stable AAD therapy for at least 6 months, objective AF burden below an
      established threshold, and the absence of non-pharmacologic therapies.
      Participants were genotyped for common AF susceptibility alleles at chromosomes
      4q25 (near PITX2), 16q22 (in ZFHX3), and 1q21 (in KCNN3), and common SNPs in the
      beta1-adrenergic receptor (ARDB1). Wild-type status for rs10033464 at 4q25 was
      associated with increased success of AAD therapy in patients with no or mild OSA
      (odds ratio: 10.0, 95% confidence interval: 1.03 to 97.5; p < 0.05), but did not
      influence response to AAD therapy in those with moderate-severe OSA. A similar
      trend was observed for rs1801252 on ARDB1. CONCLUSION: In this hypothesis
      generating pilot study of predominantly Caucasian men, the effect on AF response
      to AAD therapy of rs10033464 at 4q25 varied based on OSA status. The impact of
      genotype on AAD efficacy may be greatest in mild OSA and attenuated in more
      severe disease.

PMID- 24910552
TI  - Sleep disordered breathing in isolated unilateral and bilateral diaphragmatic
      dysfunction.
AB  - INTRODUCTION: The effect of isolated unilateral or bilateral diaphragmatic
      dysfunction (DD), in the absence of a generalized neuromuscular disorder, on
      sleep disordered breathing (SDB) is not well understood. The type of positive
      airway pressure (PAP) device needed to treat SDB in patients with isolated DD is
      also not well established. METHODS: We retrospectively analyzed data on patients
      with isolated unilateral or bilateral DD who were referred for polysomnography
      (PSG) for clinical symptoms or abnormal oximetry between 1994 and 2006. RESULTS:
      We found 66 patients who met criteria, of whom 74.2% were males with an average
      age of 58.8 +/- 10.9 years. 56 had isolated unilateral DD, and 10 had isolated
      bilateral DD. All had significant SDB with an apnea-hypopnea index (AHI) of 26.6
      +/- 28.4. There were no significant differences in PSG measures, arterial blood
      gas analysis, pulmonary function tests, or echocardiographic data, except for
      lower maximal inspiratory pressure in patients with bilateral DD compared to
      unilateral DD (40.2% +/- 17.8% vs. 57.7% +/- 20.5%, p = 0.02). Control of SDB
      with continuous PAP (CPAP) was possible in only 37.9% of patients with the rest
      requiring bilevel PAP (BPAP). Patients with isolated bilateral DD and SDB were
      6.8 times more likely to fail CPAP than those with unilateral DD (p = 0.03).
      CONCLUSIONS: Most patients with isolated DD failed CPAP and required BPAP.
      Patients with bilateral DD were more likely to require BPAP than those with
      unilateral DD. Patients with isolated DD should be considered for in-lab
      titration to determine adequacy of therapy.

PMID- 24910553
TI  - Hypercapnia is a key correlate of EEG activation and daytime sleepiness in
      hypercapnic sleep disordered breathing patients.
AB  - BACKGROUND: The key determinants of daytime drowsiness in sleep disordered
      breathing (SDB) are unclear. Hypercapnia has not been examined as a potential
      contributor due to the lack of reliable measurement during sleep. To overcome
      this limitation, we studied predominantly hypercapnic SDB patients to investigate
      the role of hypercapnia on EEG activation and daytime sleepiness. METHODS: We
      measured overnight polysomnography (PSG), arterial blood gases, and Epworth
      Sleepiness Scale in 55 severe SDB patients with obesity hypoventilation syndrome
      or overlap syndrome (COPD+ obstructive sleep apnea) before and ~3 months after
      positive airway pressure (PAP) treatment. Quantitative EEG analyses were
      performed, and the Delta/ Alpha ratio was used as an indicator of EEG activation.
      RESULTS: After the PAP treatment, these patients showed a significant decrease in
      their waking pCO(2), daytime sleepiness, as well as all key breathing/oxygenation
      parameters during sleep. Overnight Delta/Alpha ratio of EEG was significantly
      reduced. There is a significant cross-correlation between a reduced wake pCO(2),
      a faster (more activated) sleep EEG (reduced Delta/Alpha ratio) and reduced
      daytime sleepiness (all p < 0.05) with PAP treatment. Multiple regression
      analyses showed the degree of change in hypercapnia to be the only significant
      predictor for both ESS and Delta/ Alpha ratio. CONCLUSIONS: Hypercapnia is a key
      correlate of EEG activation and daytime sleepiness in hypercapnic SDB patients.
      The relationship between hypercapnia and sleepiness may be mediated by reduced
      neuro-electrical brain activity.

PMID- 24910554
TI  - Carbon dioxide in sleep medicine: the next frontier for measurement,
      manipulation, and research.

PMID- 24910555
TI  - Obesity. Introduction.

PMID- 24910556
TI  - Thinking evolutionarily about obesity.
AB  - Obesity, diabetes, and metabolic syndrome are growing worldwide health concerns,
      yet their causes are not fully understood. Research into the etiology of the
      obesity epidemic is highly influenced by our understanding of the evolutionary
      roots of metabolic control. For half a century, the thrifty gene hypothesis,
      which argues that obesity is an evolutionary adaptation for surviving periods of
      famine, has dominated the thinking on this topic. Obesity researchers are often
      not aware that there is, in fact, limited evidence to support the thrifty gene
      hypothesis and that alternative hypotheses have been suggested. This review
      presents evidence for and against the thrifty gene hypothesis and introduces
      readers to additional hypotheses for the evolutionary origins of the obesity
      epidemic. Because these alternate hypotheses imply significantly different
      strategies for research and clinical management of obesity, their consideration
      is critical to halting the spread of this epidemic. 

PMID- 24910557
TI  - The pathogenesis of obesity from a genomic and systems biology perspective.
AB  - The recent obesity epidemic has imposed significant health, economical, and
      societal concerns. However, effective preventive and therapeutic strategies are
      currently lacking, primarily due to a lack of comprehensive understanding of the
      underlying molecular mechanisms. Recent genome-wide scans of genetic variants,
      transcriptome, and epigenome have uncovered >50 genetic loci that predispose
      individuals to obesity and revealed hundreds of genes with altered
      transcriptional activity and/or epigenetic variations in obesity-related tissues
      upon various environmental challenges such as high caloric diets, lack of
      physical activity, and environmental chemicals. These discoveries highlight the
      importance of genes involved in the control of energy homeostasis and food intake
      by the central nervous system, as well as genes contributing to lipid metabolism,
      adipogenesis, fat cell differentiation, and immune response in peripheral
      tissues, in obesity development. Future studies that are directed to obtain a
      more comprehensive, systems-level understanding of disease mechanisms and that
      test novel therapeutic strategies aiming at systems-level normalization of the
      obesity-related molecular alterations are warranted. 

PMID- 24910558
TI  - A dangerous duo in adipose tissue: high-mobility group box 1 protein and
      macrophages.
AB  - High-mobility group box 1 (HMGB1) protein first made headlines 40 years ago as a
      non-histone nuclear protein that regulates gene expression. Not so long ago, it
      was also shown that HMGB1 has an additional surprising function. When released
      into the extracellular milieu, HMGB1 triggers an inflammatory response by serving
      as an endogenous danger signal. The pro-inflammatory role of HMGB1 is now well
      established and has been associated with several diseases, including sepsis,
      rheumatoid arthritis, and atherosclerosis. Yet very little is known about its
      role in obesity, wherein adipose tissue is typified by a persistent, smoldering
      inflammatory response instigated by high macrophage infiltrate that potentiates
      the risk of obesity-associated comorbidities. This mini-review focuses on the
      putative causal relationship between HMGB1 and macrophage pro-inflammatory
      activation in pathologically altered adipose tissue associated with obesity. 

PMID- 24910559
TI  - Effects of dairy on metabolic syndrome parameters: a review.
AB  - Metabolic syndrome (MetS), characterized by central obesity, dyslipidemias,
      hypertension, and hyperglycemia, impacts 34 percent of the U.S. adult population.
      MetS has been demonstrated to be affected by dietary components. Data from
      epidemiological studies and clinical interventions suggest that one or more dairy
      components might directly affect MetS parameters. For example, calcium has been
      postulated to reduce body weight by modulating vitamin D concentrations in plasma
      and therefore attenuating intracellular calcium effects in activating genes
      involved in fatty acid synthesis and reducing those involved in lipolysis.
      Peptides present in milk have been associated with the inhibition of angiotensin
      converting enzyme and, therefore, with blood pressure reductions. Branched chain
      amino acids may increase post-prandial insulin secretion and regulate plasma
      glucose levels, and leucine, an abundant amino acid in milk, may be responsible
      for decreased plasma glucose through modulation of mTOR. Through different
      proposed mechanisms, dairy nutrients may target all components of MetS. 

PMID- 24910560
TI  - A temperature hypothesis of hypothalamus-driven obesity.
AB  - Obesity is a metabolic state in which excess fat is accumulated in peripheral
      tissues, including the white adipose tissue, muscle, and liver. Sustained obesity
      has profound consequences on one's life, which can span from superficial
      psychological symptoms to serious co-morbidities that may dramatically diminish
      both the quality and length of life. Obesity and related metabolic disorders
      account for the largest financial burden on the health care system. Together,
      these issues make it imperative that obesity be cured or prevented. Despite the
      increasing wealth of knowledge on the etiology of obesity (see below), there is
      no successful medical strategy that is available for the vast majority of
      patients. We suggest that brain temperature control may be a crucial component in
      obesity development and that shortcutting the brain metabolic centers by
      hypothalamic temperature alterations in a non-invasive remote manner will provide
      a revolutionary approach to the treatment of obesity. 

PMID- 24910561
TI  - Clinical management of patients presenting with non-adjustable gastric band
      (NAGB) complications.
AB  - BACKGROUND: A number of bariatric surgical procedures have been developed to
      manage morbid obesity and related co-morbidities. The non-adjustable gastric band
      (NAGB) was one such procedure that created restriction to food intake by gastric
      segmentation. Benefits of the procedure included a low risk of perioperative
      complications and substantial early weight loss. Unfortunately, the long term
      results of NAGB include a high incidence of complications and failure to maintain
      weight loss. The purpose of this study was to examine the presentation, workup,
      and treatment of patients presenting with complications following NAGB placement.
      METHODS: A retrospective review of the diagnosis and management of 11 patients
      who presented with complications related to NAGB placement. RESULTS: All patients
      presented with some degree of proximal gastric outlet obstruction. The majority
      of patients (8/11) presented with vomiting as the main complaint. Other
      complaints included intolerance to solids, liquids, and reflux. Only 2/11
      patients presented with weight loss since undergoing NAGB placement, while the
      remainder had weight regain to their pre-NAGB level and above. Depending on
      clinical presentation, desire for additional weight loss and co-morbid
      conditions, patients underwent a variety of treatments. This included NAGB
      removal (endoscopic, laparo-endoscopic, and laparoscopic) as well as conversion
      to another bariatric procedure (sleeve gastrectomy, Roux-en-Y gastric bypass).
      CONCLUSION: Patients with NAGB complications present with symptoms related to a
      proximal gastric outlet obstruction, related to constriction imposed by the band.
      This may result in severe food and liquid intolerance and subsequent weight loss,
      but more likely results in maladaptive eating and subsequent weight gain. Optimal
      therapy involves removal of the NAGB. Laparoscopic conversion to another
      bariatric procedure, optimally a Roux-en-Y gastric bypass, is warranted to treat
      morbid obesity and associated co-morbidities.

PMID- 24910562
TI  - Obesity: from public health to public policy: an interview with Marlene Schwartz,
      PhD.

PMID- 24910564
TI  - Clinical decision support: effectiveness in improving quality processes and
      clinical outcomes and factors that may influence success.
AB  - The use of electronic health records has skyrocketed following the 2009 HITECH
      Act, which provides financial incentives to health care providers for the
      "meaningful use" of electronic medical record systems. An important component of
      the "Meaningful Use" legislation is the integration of Clinical Decision Support
      Systems (CDSS) into the computerized record, providing up-to-date medical
      knowledge and evidence-based guidance to the physician at the point of care. As
      reimbursement is increasingly tied to process and clinical outcomes, CDSS will be
      integral to future medical practice. Studies of CDSS indicate improvement in
      preventive services, appropriate care, and clinical and cost outcomes with strong
      evidence for CDSS effectiveness in process measures. Increasing provider
      adherence to CDSS recommendations is essential in improving CDSS effectiveness,
      and factors that influence adherence are currently under study. 

PMID- 24910563
TI  - Genetic and epigenetic regulation of the brain-derived neurotrophic factor in the
      central nervous system.
AB  - The BDNF is required for the development and proper function of the central
      nervous system, where it is involved in a variety of neural and molecular events
      relevant to cognition, learning, and memory processes. Although only a functional
      mature protein is synthesized, the human BDNF gene possesses an extensive
      structural complexity, including the presence of multiple promoters, splicing
      events, and 3'UTR poly-adenylation sites, resulting in an intricate
      transcriptional regulation and numerous messengers RNA. Recent data support
      specific cellular roles of these transcripts. Moreover, a central role of
      epigenetic modifications on the regulation of BDNF gene transcription is also
      emerging. The present essay aims to summarize the published information on the
      matter, emphasizing their possible implications in health and disease or in the
      treatment of different neurologic and psychiatric disorders. 

PMID- 24910565
TI  - Anticoagulation for the acute management of ischemic stroke.
AB  - Few prospective studies support the use of anticoagulation during the acute phase
      of ischemic stroke, though observational data suggest a role in certain
      populations. Depending on the mechanism of stroke, systemic anticoagulation may
      prevent recurrent cerebral infarction, but concomitantly carries a risk of
      hemorrhagic transformation. In this article, we describe a case where
      anticoagulation shows promise for ischemic stroke and review the evidence that
      has discredited its use in some circumstances while showing its potential in
      others. 

PMID- 24910566
TI  - How to learn effectively in medical school: test yourself, learn actively, and
      repeat in intervals.
AB  - Students in medical school often feel overwhelmed by the excessive amount of
      factual knowledge they are obliged to learn. Although a large body of research on
      effective learning methods is published, scientifically based learning strategies
      are not a standard part of the curriculum in medical school. Students are largely
      unaware of how to learn successfully and improve memory. This review outlines
      three fundamental methods that benefit learning: the testing effect, active
      recall, and spaced repetition. The review summarizes practical learning
      strategies to learn effectively and optimize long-term retention of factual
      knowledge. 

PMID- 24910568
TI  - Fabrication of porous silicon nanowires by MACE method in HF/H2O2/AgNO3 system at
      room temperature.
AB  - In this paper, the moderately and lightly doped porous silicon nanowires (PSiNWs)
      were fabricated by the 'one-pot procedure' metal-assisted chemical etching (MACE)
      method in the HF/H2O2/AgNO3 system at room temperature. The effects of H2O2
      concentration on the nanostructure of silicon nanowires (SiNWs) were
      investigated. The experimental results indicate that porous structure can be
      introduced by the addition of H2O2 and the pore structure could be controlled by
      adjusting the concentration of H2O2. The H2O2 species replaces Ag(+) as the
      oxidant and the Ag nanoparticles work as catalyst during the etching. And the
      concentration of H2O2 influences the nucleation and motility of Ag particles,
      which leads to formation of different porous structure within the nanowires. A
      mechanism based on the lateral etching which is catalyzed by Ag particles under
      the motivation by H2O2 reduction is proposed to explain the PSiNWs formation. 

PMID- 24910567
TI  - On the Outcome Project.
AB  - BACKGROUND: In 2001, graduate medical education in the United States was
      renovated to better complement 21st century developments in American medicine,
      society, and culture. As in 1910, when Abraham Flexner was charged to address a
      relatively non-standardized system that lacked accountability and threatened
      credibility of the profession, Dr. David Leach led the Accreditation Council of
      Graduate Medical Education (ACGME) Outcome Project in a process that has
      substantially changed medical pedagogy in the United States. METHODS: Brief
      review of the Flexner Report of 1910 and 6 hours of interviews with leaders of
      the Outcome Project (4 hours with Dr. David Leach and 1-hour interviews with Drs.
      Paul Batalden and Susan Swing). RESULTS: Medical educational leaders and the
      ACGME concluded in the late 1990s that medical education was not preparing
      clinicians sufficiently for lifelong learning in the 21st century. A confluence
      of medical, social, and historic factors required definitions and a common
      vocabulary for teaching and evaluating medical competency. After a deliberate
      consensus-driven process, the ACGME and its leaders produced a system requiring
      greater accountability of learners and teachers, in six explicitly defined
      domains of medical "competence." While imperfect, this construct has started to
      take hold, creating a common vocabulary for longitudinal learning, from
      undergraduate to post-graduate (residency) education and in the assessment of
      performance following graduate training.

PMID- 24910569
TI  - Electrostatic complexation of polyelectrolyte and magnetic nanoparticles: from
      wild clustering to controllable magnetic wires.
AB  - We present the electrostatic complexation between polyelectrolytes and charged
      nanoparticles. The nanoparticles in solution are gamma-Fe2O3 (maghemite) spheres
      with 8.3 nm diameter and anionic surface charges. The complexation was monitored
      using three different formulation pathways such as direct mixing, dilution, and
      dialysis. In the first process, the hybrids were obtained by mixing stock
      solutions of polymers and nanoparticles. A 'destabilization state' with sharp and
      intense maximum aggregation was found at charges stoichiometry (isoelectric
      point). While on the two sides of the isoelectric point, 'long-lived stable
      clusters state' (arrested states) were observed. Dilution and dialysis processes
      were based on controlled desalting kinetics according to methods developed in
      molecular biology. Under an external magnetic field (B = 0.3 T), from dialysis at
      isoelectric point and at arrested states, cationic polyelectrolytes can 'paste'
      these magnetic nanoparticles (NPs) together to yield irregular aggregates (size
      of 100 MUm) and regular rod-like aggregates, respectively. These straight
      magnetic wires were fabricated with diameters around 200 nm and lengths comprised
      between 1 MUm and 0.5 mm. The wires can have either positive or negative charges
      on their surface. After analyzing their orientational behavior under an external
      rotating field, we also showed that the wires made from different
      polyelectrolytes have the same magnetic property. The recipe used a wide range of
      polyelectrolytes thereby enhancing the versatility and applied potentialities of
      the method. This simple and general approach presents significant perspective for
      the fabrication of hybrid functional materials. 

PMID- 24910570
TI  - A preparation approach of exploring cluster ion implantation: from ultra-thin
      carbon film to graphene.
AB  - Based on the extensive application of 2 * 1.7MV Tandetron accelerator, a low
      energy cluster chamber has been built to explore for synthesizing graphene. Raman
      spectrum and atomic force microscopy (AFM) show that an amorphous carbon film in
      nanometer was deposited on the silicon by C4 cluster implantation. And we
      replaced the substrate with Ni/SiO2/Si and measured the thickness of Ni film by
      Rutherford backscattering spectrometry (RBS). Combined with suitable anneal
      conditions, these samples implanted by various small carbon clusters were made to
      grow graphene. Results from Raman spectrum reveal that few-layer graphene were
      obtained and discuss whether I G/I 2D can contribute to explain the relationship
      between the number of graphene layers and cluster implantation dosage. 

PMID- 24910572
TI  - Formation mechanisms for the dominant kinks with different angles in InP
      nanowires.
AB  - The morphologies and microstructures of kinked InP nanowires (NWs) prepared by
      solid-source chemical vapor deposition method were examined using scanning
      electron microscopy (SEM) and high-resolution transmission electron microscopy
      (HRTEM). Statistical analysis and structural characterization reveal that four
      different kinds of kinks are dominant in the grown InP NWs with a bending angle
      of approximately 70 degrees , 90 degrees , 110 degrees , and 170 degrees ,
      respectively. The formation mechanisms of these kinks are discussed.
      Specifically, the existence of kinks with bending angles of approximately 70
      degrees  and 110 degrees  are mainly attributed to the occurrence of stacking
      faults and nanotwins in the NWs, which could easily form by the glide of {111}
      planes, while approximately 90 degrees  kinks result from the local
      amorphorization of InP NWs. Also, approximately 170 degrees  kinks are mainly
      caused by small-angle boundaries, where the insertion of extra atomic planes
      could make the NWs slightly bent. In addition, multiple kinks with various angles
      are also observed. Importantly, all these results are beneficial to understand
      the formation mechanisms of kinks in compound semiconductor NWs, which could
      guide the design of nanostructured materials, morphologies, microstructures,
      and/or enhanced mechanical properties. 

PMID- 24910571
TI  - Gold nanoparticles grown inside carbon nanotubes: synthesis and electrical
      transport measurements.
AB  - The hybrid structures composed of gold nanoparticles and carbon nanotubes were
      prepared using porous alumina membranes as templates. Carbon nanotubes were
      synthesized inside the pores of these templates by the non-catalytic
      decomposition of acetylene. The inner cavity of the supported tubes was used as
      nanoreactors to grow gold particles by impregnation with a gold salt, followed by
      a calcination-reduction process. The samples were characterized by transmission
      electron microscopy and X-ray energy dispersion spectroscopy techniques. The
      resulting hybrid products are mainly encapsulated gold nanoparticles with
      different shapes and dimensions depending on the concentration of the gold
      precursor and the impregnation procedure. In order to understand the electronic
      transport mechanisms in these nanostructures, their conductance was measured as a
      function of temperature. The samples exhibit a 'non-metallic' temperature
      dependence where the dominant electron transport mechanism is 1D hopping.
      Depending on the impregnation procedure, the inclusion of gold nanoparticles
      inside the CNTs can introduce significant changes in the structure of the tubes
      and the mechanisms for electronic transport. The electrical resistance of these
      hybrid structures was monitored under different gas atmospheres at ambient
      pressure. Using this hybrid nanostructures, small amounts of acetylene and
      hydrogen were detected with an increased sensibility compared with pristine
      carbon nanotubes. Although the sensitivity of these hybrid nanostructures is
      rather low compared to alternative sensing elements, their response is remarkably
      fast under changing gas atmospheres. 

PMID- 24910573
TI  - Transformation of ZnO polycrystalline sheets into hexagon-like mesocrystalline
      ZnO rods (tubes) under ultrasonic vibration.
AB  - The mesoscale assembly process is sensitive to additives that can modify the
      interactions of the crystal nucleus and the developing crystals with solid
      surfaces and soluble molecules. However, the presence of additives is not a
      prerequisite for the mesoscale transformation process. In this study, ZnO sheet
      networks were synthesized on Al foils by a hydrothermal process. Scanning
      electron microscopy and transmission electron microscopy images confirmed that
      under ultrasonic vibration, monolithic polycrystalline ZnO sheets transformed
      into hexagon-like mesocrystalline tubes or rods. The formation mechanism was
      discussed. 

PMID- 24910574
TI  - Albumin-fatty acid interactions at monolayer interface.
AB  - The fluid mosaic model of Singer and Nicolson in 1972 shows how proteins are
      embedded in membranes. To elucidate the interactions between proteins and the
      surrounding lipids, stearic acid (SA) and bovine serum albumin (BSA) were used as
      lipid-protein components to mimic the normal membrane bilayer environment using
      the Langmuir-Blodgett technique. Surface pressure (pi)-molecular area (A)
      isotherms were recorded for the SA monolayer in the presence of BSA on water. The
      mixed monolayer was successfully transferred onto an oxidized silicon wafer and
      imaged by tapping mode atomic force microscopy (AFM). Miscibility,
      compressibility and thermodynamic stability of the mixed system were examined. A
      large negative deviation of A ex, together with the minimum value of DeltaG ex,
      was observed when the mole fraction of BSA (X BSA) was 0.8, indicating this to be
      the most stable mixture. In a compressibility analysis, X BSA was observed at
      below 50 mN m(-1), denoting a liquid-expanded phase and showing the occurrence of
      a strong interaction of SA with BSA molecules in this phase. AFM observations
      supported the quantitative data indicating that BSA was strongly attracted onto
      the membrane surface as predicted. 

PMID- 24910575
TI  - Fabrication of ZnCoO nanowires and characterization of their magnetic properties.
AB  - Hydrogen-treated ZnCoO shows magnetic behavior, which is related to the formation
      of Co-H-Co complexes. However, it is not well known how the complexes are
      connected to each other and with what directional behavior they are ordered. In
      this point of view, ZnCoO nanowire is an ideal system for the study of the
      magnetic anisotropy. ZnCoO nanowire was fabricated by trioctylamine solution
      method under different ambient gases. We found that the oxidation of
      trioctylamine plays an essential role on the synthesis of high-quality ZnCoO
      nanowires. The hydrogen injection to ZnCoO nanowires induced ferromagnetism with
      larger magnetization than ZnCoO powders, while becoming paramagnetic after vacuum
      heat treatment. Strong ferromagnetism of nanowires can be explained by the
      percolation of Co-H-Co complexes along the c-axis. 

PMID- 24910576
TI  - Improvement of the physical properties of ZnO/CdTe core-shell nanowire arrays by
      CdCl2 heat treatment for solar cells.
AB  - CdTe is an important compound semiconductor for solar cells, and its use in
      nanowire-based heterostructures may become a critical requirement, owing to the
      potential scarcity of tellurium. The effects of the CdCl2 heat treatment are
      investigated on the physical properties of vertically aligned ZnO/CdTe core-shell
      nanowire arrays grown by combining chemical bath deposition with close space
      sublimation. It is found that recrystallization phenomena are induced by the
      CdCl2 heat treatment in the CdTe shell composed of nanograins: its crystallinity
      is improved while grain growth and texture randomization occur. The presence of a
      tellurium crystalline phase that may decorate grain boundaries is also revealed.
      The CdCl2 heat treatment further favors the chlorine doping of the CdTe shell
      with the formation of chlorine A-centers and can result in the passivation of
      grain boundaries. The absorption properties of ZnO/CdTe core-shell nanowire
      arrays are highly efficient, and more than 80% of the incident light can be
      absorbed in the spectral range of the solar irradiance. The resulting
      photovoltaic properties of solar cells made from ZnO/CdTe core-shell nanowire
      arrays covered with CuSCN/Au back-side contact are also improved after the CdCl2
      heat treatment. However, recombination and trap phenomena are expected to
      operate, and the collection of the holes that are mainly photo-generated in the
      CdTe shell from the CuSCN/Au back-side contact is presumably identified as the
      main critical point in these solar cells. 

PMID- 24910578
TI  - Consistent melting behavior induced by Joule heating between Ag microwire and
      nanowire meshes.
AB  - The melting behavior of an Ag microwire mesh induced by Joule heating was
      numerically investigated and compared with that of the corresponding Ag nanowire
      mesh with the same structure but different geometrical and physical properties of
      the wire itself. According to the relationship of melting current and melting
      voltage during the melting process, a similar repetitive zigzag pattern in
      melting behavior was discovered in both meshes. On this basis, a dimensionless
      parameter defined as figure of merit was proposed to characterize the current
      carrying ability of the mesh. The consistent feature of figure of merit in both
      meshes indicates that the melting behavior of the Ag nanowire mesh can be
      predicted from the present results of the corresponding Ag microwire mesh with
      the same structure but made from a different wire (e.g., different size,
      different material) through simple conversion. The present findings can provide
      fundamental insight into the reliability analysis on the metallic nanowire mesh
      based transparent conductive electrode. 

PMID- 24910577
TI  - Phytosynthesis of nanoparticles: concept, controversy and application.
AB  - Nanotechnology is an exciting and powerful discipline of science; the altered
      properties of which have offered many new and profitable products and
      applications. Agriculture, food and medicine sector industries have been
      investing more in nanotechnology research. Plants or their extracts provide a
      biological synthesis route of several metallic nanoparticles which is more eco
      friendly and allows a controlled synthesis with well-defined size and shape. The
      rapid drug delivery in the presence of a carrier is a recent development to treat
      patients with nanoparticles of certain metals. The engineered nanoparticles are
      more useful in increasing the crop production, although this issue is still in
      infancy. This is simply due to the unprecedented and unforeseen health hazard and
      environmental concern. The well-known metal ions such as zinc, iron and copper
      are essential constituents of several enzymes found in the human system even
      though the indiscriminate use of similar other metal nanoparticle in food and
      medicine without clinical trial is not advisable. This review is intended to
      describe the novel phytosynthesis of metal and metal oxide nanoparticles with
      regard to their shape, size, structure and diverse application in almost all
      fields of medicine, agriculture and technology. We have also emphasized the
      concept and controversial mechanism of green synthesis of nanoparticles. 

PMID- 24910579
TI  - Improving Positive Airway Pressure Adherence in Children.

PMID- 24910580
TI  - Correcting systemic deficiencies in our scientific infrastructure.
AB  - Scientific method is inherently self-correcting. When different hypotheses are
      proposed, their study would result in the rejection of the invalid ones. If the
      study of a competing hypothesis is prevented because of the faith in an
      unverified one, scientific progress is stalled. This has happened in the study of
      low dose radiation. Though radiation hormesis was hypothesized to reduce cancers
      in 1980, it could not be studied in humans because of the faith in the unverified
      linear no-threshold model hypothesis, likely resulting in over 15 million
      preventable cancer deaths worldwide during the past two decades, since evidence
      has accumulated supporting the validity of the phenomenon of radiation hormesis.
      Since our society has been guided by scientific advisory committees that
      ostensibly follow the scientific method, the long duration of such large
      casualties is indicative of systemic deficiencies in the infrastructure that has
      evolved in our society for the application of science. Some of these deficiencies
      have been identified in a few elements of the scientific infrastructure, and
      remedial steps suggested. Identifying and correcting such deficiencies may
      prevent similar tolls in the future. 

PMID- 24910582
TI  - Non-linear adaptive phenomena which decrease the risk of infection after pre
      exposure to radiofrequency radiation.
AB  - Substantial evidence indicates that adaptive response induced by low doses of
      ionizing radiation can result in resistance to the damage caused by a
      subsequently high-dose radiation or cause cross-resistance to other non-radiation
      stressors. Adaptive response contradicts the linear-non-threshold (LNT) dose
      response model for ionizing radiation. We have previously reported that exposure
      of laboratory animals to radiofrequency radiation can induce a survival adaptive
      response. Furthermore, we have indicated that pre-exposure of mice to
      radiofrequency radiation emitted by a GSM mobile phone increased their resistance
      to a subsequent Escherichia coli infection. In this study, the survival rates in
      animals receiving both adapting (radiofrequency) and challenge dose (bacteria)
      and the animals receiving only the challenge dose (bacteria) were 56% and 20%,
      respectively. In this light, our findings contribute to the assumption that
      radiofrequency-induced adaptive response can be used as an efficient method for
      decreasing the risk of infection in immunosuppressed irradiated individuals. The
      implication of this phenomenon in human's long term stay in the space is also
      discussed. 

PMID- 24910583
TI  - Evaluation of the alamarblue assay for adherent cell irradiation experiments.
AB  - The AlamarBlue assay is based on fluorometric detection of metabolic
      mitochondrial activity of cells. In this study, we determined the methodology for
      application of the assay to radiation response experiments in 96-well plates.
      AlamarBlue was added and its reduction measured 7 hours later. Selection of the
      initial number of plated cells was important so that the number of proliferating
      cells remains lower than the critical number that produced full AlamarBlue
      reduction (plateau phase) at the time points of measurements. Culture medium was
      replaced twice a week to avoid suppression of viability due to nutrient
      competition and metabolic waste accumulation. There was no need to replace
      culture medium before adding AlamarBlue. Cell proliferation continued after
      irradiation and the suppression effect on cell viability was most evident on day
      8. At this time point, by comparing measurements from irradiated vs. non
      irradiated cells, for various dose levels, a viability dose response curve was
      plotted. Immediately after the 8(th) day (nadir), cells started to re-grow at a
      rate inversely related to the radiation dose. By comparing measurements at the
      time point of nadir vs. a convenient subsequent time point, re-growth dose
      response abilities were plotted, simulating clonogenic assays. 

PMID- 24910584
TI  - Non-monotonic dose responses in studies of endocrine disrupting chemicals:
      bisphenol a as a case study.
AB  - Non-monotonic dose response curves (NMDRCs) have been demonstrated for natural
      hormones and endocrine disrupting chemicals (EDCs) in a variety of biological
      systems including cultured cells, whole organ cultures, laboratory animals and
      human populations. The mechanisms responsible for these NMDRCs are well known,
      typically related to the interactions between the ligand (hormone or EDC) and a
      hormone receptor. Although there are hundreds of examples of NMDRCs in the EDC
      literature, there are claims that they are not 'common enough' to influence the
      use of high-to-low dose extrapolations in risk assessments. Here, we chose
      bisphenol A (BPA), a well-studied EDC, to assess the frequency of non-monotonic
      responses. Our results indicate that NMDRCs are common in the BPA literature,
      occurring in greater than 20% of all experiments and in at least one endpoint in
      more than 30% of all studies we examined. We also analyzed the types of endpoints
      that produce NMDRCs in vitro and factors related to study design that influence
      the ability to detect these kinds of responses. Taken together, these results
      provide strong evidence for NMDRCs in the EDC literature, specifically for BPA,
      and question the current risk assessment practice where 'safe' low doses are
      predicted from high dose exposures. 

PMID- 24910585
TI  - Low dose radiation adaptive protection to control neurodegenerative diseases.
AB  - Concerns have been expressed recently regarding the observed increased DNA damage
      from activities such as thinking and exercise. Such concerns have arisen from an
      incomplete accounting of the full effects of the increased oxidative damage. When
      the effects of the induced adaptive protective responses such as increased
      antioxidants and DNA repair enzymes are taken into consideration, there would be
      less endogenous DNA damage during the subsequent period of enhanced defenses,
      resulting in improved health from the thinking and exercise activities. Low dose
      radiation (LDR), which causes oxidative stress and increased DNA damage,
      upregulates adaptive protection systems that may decrease diseases in an
      analogous manner. Though there are ongoing debates regarding LDR's
      carcinogenicity, with two recent advisory committee reports coming to opposite
      conclusions, data published since the time of the reports have overwhelmingly
      ruled out its carcinogenicity, paving the way for consideration of its potential
      use for disease reduction. LDR adaptive protection is a promising approach to
      control neurodegenerative diseases, for which there are no methods of prevention
      or cure. Preparation of a compelling ethics case would pave the way for LDR
      clinical studies and progress in dealing with neurodegenerative diseases. 

PMID- 24910581
TI  - Nonlinear effects of nanoparticles: biological variability from hormetic doses,
      small particle sizes, and dynamic adaptive interactions.
AB  - Researchers are increasingly focused on the nanoscale level of organization where
      biological processes take place in living systems. Nanoparticles (NPs, e.g., 1
      100 nm diameter) are small forms of natural or manufactured source material whose
      properties differ markedly from those of the respective bulk forms of the "same"
      material. Certain NPs have diagnostic and therapeutic uses; some NPs exhibit low
      dose toxicity; other NPs show ability to stimulate low-dose adaptive responses
      (hormesis). Beyond dose, size, shape, and surface charge variations of NPs evoke
      nonlinear responses in complex adaptive systems. NPs acquire unique size
      dependent biological, chemical, thermal, optical, electromagnetic, and atom-like
      quantum properties. Nanoparticles exhibit high surface adsorptive capacity for
      other substances, enhanced bioavailability, and ability to cross otherwise
      impermeable cell membranes including the blood-brain barrier. With super-potent
      effects, nano-forms can evoke cellular stress responses or therapeutic effects
      not only at lower doses than their bulk forms, but also for longer periods of
      time. Interactions of initial effects and compensatory systemic responses can
      alter the impact of NPs over time. Taken together, the data suggest the need to
      downshift the dose-response curve of NPs from that for bulk forms in order to
      identify the necessarily decreased no-observed-adverse-effect-level and hormetic
      dose range for nanoparticles. 

PMID- 24910586
TI  - Commentary: ethical issues of current health-protection policies on low-dose
      ionizing radiation.
AB  - The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based
      on the assumption that every radiation dose increment constitutes increased
      cancer risk for humans. The risk is hypothesized to increase linearly as the
      total dose increases. While this model is the basis for radiation safety
      regulations, its scientific validity has been questioned and debated for many
      decades. The recent memorandum of the International Commission on Radiological
      Protection admits that the LNT-model predictions at low doses are "speculative,
      unproven, undetectable and 'phantom'." Moreover, numerous experimental,
      ecological, and epidemiological studies show that low doses of sparsely-ionizing
      or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human
      health (hormesis/adaptive response). The present LNT-model-based regulations
      impose excessive costs on the society. For example, the median-cost medical
      program is 5000 times more cost-efficient in saving lives than controlling
      radiation emissions. There are also lives lost: e.g., following Fukushima
      accident, more than 1000 disaster-related yet non-radiogenic premature deaths
      were officially registered among the population evacuated due to radiation
      concerns. Additional negative impacts of LNT-model-inspired radiophobia include:
      refusal of some patients to undergo potentially life-saving medical imaging;
      discouragement of the study of low-dose radiation therapies; motivation for
      radiological terrorism and promotion of nuclear proliferation. 

PMID- 24910587
TI  - Remedy for radiation fear - discard the politicized science.
AB  - Seeking a remedy for the radiation fear in Japan, the author re-examined an
      article on radiation hormesis. It describes the background for this fear and
      evidence in the first UNSCEAR report of a reduction in leukemia of the Hiroshima
      survivors in the low dose zone. The data are plotted and dose-response models are
      drawn. While UNSCEAR suggested the extra leukemia incidence is proportional to
      radiation dose, the data are consistent with a hormetic J-shape and a threshold
      at about 100 rem (1 Sv). UNSCEAR data on lifespan reduction of mammals exposed
      continuously to gamma rays indicate a 2 gray/year threshold. This contradicts the
      conceptual basis for radiation protection and risk determination established in
      1956-58. In this paper, beneficial effects and thresholds for harmful effects are
      discussed, and the biological mechanism is explained. The key point: the rate of
      DNA damage (double-strand breaks) caused by background radiation is 1000 times
      less than the endogenous (spontaneous) rate. It is the effect of radiation on an
      organism's very powerful adaptive protection systems that determines the dose
      response characteristic. Low radiation up-regulates the protection systems, while
      high radiation impairs these systems. The remedy for radiation fear is to expose
      and discard the politicized science. 

PMID- 24910589
TI  - Impact of a Culturally Sensitive Health Self-Empowerment Workshop Series on
      Health Behaviors/Lifestyles, BMI, and Blood Pressure of Culturally Diverse
      Overweight/Obese Adults.
AB  - OBJECTIVE: Examine the impact of the Health Self-Empowerment Theory-based,
      culturally sensitive Health Self-Empowerment (HSE) Workshop Series to Modify and
      Prevent Obesity on levels of health promoting (health-smart) behaviors,
      motivators of and barriers to these behaviors, health promoting lifestyle
      variables, and health status indicators (Body Mass Index [BMI] and blood
      pressure) among a culturally diverse sample of overweight/obese adults from
      mostly low income households. DESIGN: 153 overweight/obese adults participated in
      an Immediate Treatment (IT) Group (n = 100) or a Waitlist Control (WC) Group (n =
      53). RESULTS: Post-intervention, the IT Group compared to the WC Group reported
      (a) significantly higher engagement in physical activity and healthy eating, (b)
      significantly less intake of calories, total fat, transfat, saturated fat, sugar,
      and added sugar, (c) significantly higher motivators for engaging in two of four
      specific health-smart behaviors, (d) significantly lower barriers to engaging in
      three of four specific health-smart behaviors, and (e) significantly lower BMI
      and systolic blood pressure. CONCLUSION: The HSE Workshop Series may be an
      effective intervention for treating and preventing obesity among diverse low
      income adults - individuals who often perceive/experience limited power over
      their health. Health care providers, particularly physicians, have important
      health empowerment roles in this intervention.

PMID- 24910590
TI  - An exploratory study of HIV-prevention advocacy by persons in HIV care in Uganda.
AB  - To explore how people living with HIV (PLHIV) and in care encourage others to
      adopt HIV-protective behaviours, we conducted in-depth interviews with a
      purposive sample of 40 HIV clinic patients in Kampala, Uganda. Content analysis
      was used to examine the message content, trigger events, and outcomes of HIV
      prevention advocacy events initiated by the HIV clients with members of their
      social networks. The content themes included encouraging specific behaviours,
      such as HIV testing and treatment, condom use and non-promiscuity, as well as
      more general cautionary messages about protecting oneself from HIV infection.
      Common triggers for bringing up HIV-prevention advocacy information in a
      discussion or conversation included: wanting to prevent the targeted person from
      'falling into the same problems,' wanting to benefit oneself with regard to
      avoiding re-infection, out of concern that the target would engage in higher-risk
      behaviour, due to observed changes in the target's health, and to convey
      information after receiving treatment at the clinic. The participants mostly
      reported positive or neutral responses to these advocacy events; negative
      responses were rare. Interventions to empower PLHIV to be agents of change could
      represent a new frontier for HIV prevention.

PMID- 24910591
TI  - Reciprocal functional interactions between the brainstem and the lower spinal
      cord.
AB  - The interplay of the neuronal discharge patterns regarding respiration and
      locomotion was investigated using electrophysiological techniques in a
      decerebrate and arterially perfused in situ mouse preparation. The phrenic,
      tibial, and/or peroneal nerve discharge became clearly organized into discharge
      episodes of increasing frequency and duration, punctuated by periods of
      quiescence as the perfusion flow rate increased at room temperature. The
      modulated sympathetic tone induced by the hyperoxic/normocapnic state was found
      to activate the locomotor pattern generator (LPG) via descending pathways and
      generate a left and right alternating discharge during discharge episodes in the
      motor nerves. The rhythm coupling of respiration and locomotion occurred at a 1:1
      frequency ratio. Although the phrenic discharge synchronized with the tibial
      discharge at all flow rates tested, the time lag between peaks of the two
      discharges during locomotion was ~400 ms rather than ~200 ms, suggesting spinal
      feedback via ascending pathways. The incidence of the phrenic and tibial
      discharge episodes decreased by ~50% after spinalization at the twelfth thoracic
      cord and the respiratory rhythm was more regular. These results indicate that:
      (i) locomotion can be generated in a hyperoxic/normocapnic state induced by
      specific respiratory conditions, (ii) the central mechanism regarding entrainment
      of respiratory and locomotor rhythms relies on spinal feedback via ascending
      pathways, initiated by the activated LPG generating locomotion, and (iii) the
      increase in respiratory rate seen during locomotion is caused not only by
      afferent mechanical and nociceptive inputs but also by impulses from the
      activated spinal cord producing a locomotor-like discharge via ascending
      pathways. 

PMID- 24910592
TI  - Restoration of tryptophan hydroxylase functions and serotonin content in the
      Atlantic croaker hypothalamus by antioxidant treatment during hypoxic stress.
AB  - Antioxidants are prototypical scavengers of oxygen-free radicals and have been
      shown to prevent neuroendocrine dysfunction in vertebrates during oxidative
      stress. In the present study, we investigated whether antioxidant treatment can
      reverse hypoxia-induced down-regulation of hypothalamic tryptophan hydroxylase
      (TPH) and serotonergic functions in Atlantic croaker. Hypothalamic neuronal
      contents of TPH-1 and TPH-2 proteins, serotonin (5-hydroxytryptamine, 5-HT) and
      its precursor, 5-hydroxytryptophan (5-HTP) as well as hypothalamic TPH-1 and TPH
      2 mRNA expression and TPH activity were measured in croaker after exposure to
      hypoxia and treatment with pharmacological agents. Multiple injections of N
      ethylmaleimide, a sulfhydryl alkylating agent, caused comparable decreases in
      hypothalamic TPHs functions and 5-HT contents to that induced by hypoxia exposure
      (dissolved oxygen: 1.7 mg/L for 4 weeks) which were partially restored by
      repeated injections with a nitric oxide synthase (NOS)-inhibitor and/or vitamin
      E. Double-labeled immunohistochemical results showed that TPHs and 5-HT neurons
      were co-expressed with neuronal NOS (nNOS, a neuroenzyme) that catalyzes the
      production of nitric oxide, a free radical, in hypothalamic neurons. These
      results suggest that hypoxia-induced impairment of TPH and serotonergic functions
      are mediated by nNOS and involve the generation of free radicals and a decrease
      in the antioxidant status. This study provides, to our knowledge, the first
      evidence of a protective role for an antioxidant in maintaining neural TPHs
      functions and 5-HT regulation in an aquatic vertebrate during hypoxic stress. 

PMID- 24910593
TI  - Real-time million-synapse simulation of rat barrel cortex.
AB  - Simulations of neural circuits are bounded in scale and speed by available
      computing resources, and particularly by the differences in parallelism and
      communication patterns between the brain and high-performance computers.
      SpiNNaker is a computer architecture designed to address this problem by
      emulating the structure and function of neural tissue, using very many low-power
      processors and an interprocessor communication mechanism inspired by axonal
      arbors. Here we demonstrate that thousand-processor SpiNNaker prototypes can
      simulate models of the rodent barrel system comprising 50,000 neurons and 50
      million synapses. We use the PyNN library to specify models, and the intrinsic
      features of Python to control experimental procedures and analysis. The models
      reproduce known thalamocortical response transformations, exhibit known, balanced
      dynamics of excitation and inhibition, and show a spatiotemporal spread of
      activity though the superficial cortical layers. These demonstrations are a
      significant step toward tractable simulations of entire cortical areas on the
      million-processor SpiNNaker machines in development. 

PMID- 24910588
TI  - Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive
      Oxygen Species (ROS).
AB  - Increasing evidence indicates that reactive oxygen species (ROS), consisting of
      superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative
      stress, but rather may function as signaling molecules that promote health by
      preventing or delaying a number of chronic diseases, and ultimately extend
      lifespan. While high levels of ROS are generally accepted to cause cellular
      damage and to promote aging, low levels of these may rather improve systemic
      defense mechanisms by inducing an adaptive response. This concept has been named
      mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than
      500 publications from current literature regarding such ROS-mediated low-dose
      signaling events, including calorie restriction, hypoxia, temperature stress, and
      physical activity, as well as signaling events downstream of insulin/IGF-1
      receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly
      sirtuins to culminate in control of proteostasis, unfolded protein response
      (UPR), stem cell maintenance and stress resistance. Additionally, consequences of
      interfering with such ROS signals by pharmacological or natural compounds are
      being discussed, concluding that particularly antioxidants are useless or even
      harmful. 

PMID- 24910595
TI  - How to read neuron-dropping curves?

PMID- 24910596
TI  - Corticocortical feedback increases the spatial extent of normalization.
AB  - Normalization has been proposed as a canonical computation operating across
      different brain regions, sensory modalities, and species. It provides a good
      phenomenological description of non-linear response properties in primary visual
      cortex (V1), including the contrast response function and surround suppression.
      Despite its widespread application throughout the visual system, the underlying
      neural mechanisms remain largely unknown. We recently observed that
      corticocortical feedback contributes to surround suppression in V1, raising the
      possibility that feedback acts through normalization. To test this idea, we
      characterized area summation and contrast response properties in V1 with and
      without feedback from V2 and V3 in alert macaques and applied a standard
      normalization model to the data. Area summation properties were well explained by
      a form of divisive normalization, which computes the ratio between a neuron's
      driving input and the spatially integrated activity of a "normalization pool."
      Feedback inactivation reduced surround suppression by shrinking the spatial
      extent of the normalization pool. This effect was independent of the gain
      modulation thought to mediate the influence of contrast on area summation, which
      remained intact during feedback inactivation. Contrast sensitivity within the
      receptive field center was also unaffected by feedback inactivation, providing
      further evidence that feedback participates in normalization independent of the
      circuit mechanisms involved in modulating contrast gain and saturation. These
      results suggest that corticocortical feedback contributes to surround suppression
      by increasing the visuotopic extent of normalization and, via this mechanism,
      feedback can play a critical role in contextual information processing. 

PMID- 24910594
TI  - The ER mitochondria calcium cycle and ER stress response as therapeutic targets
      in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by progressive loss of upper and lower motor neurons. Although the etiology
      remains unclear, disturbances in calcium homoeostasis and protein folding are
      essential features of neurodegeneration in this disorder. Here, we review recent
      research findings on the interaction between endoplasmic reticulum (ER) and
      mitochondria, and its effect on calcium signaling and oxidative stress. We
      further provide insights into studies, providing evidence that structures of the
      ER mitochondria calcium cycle serve as a promising targets for therapeutic
      approaches for treatment of ALS. 

PMID- 24910597
TI  - Bridging disparate symptoms of schizophrenia: a triple network dysfunction
      theory.
AB  - Schizophrenia is a complex neuropsychiatric disorder with variable
      symptomatology, traditionally divided into positive and negative symptoms, and
      cognitive deficits. However, the etiology of this disorder has yet to be fully
      understood. Recent findings suggest that alteration of the basic sense of self
      awareness may be an essential distortion of schizophrenia spectrum disorders. In
      addition, extensive research of social and mentalizing abilities has stressed the
      role of distortion of social skills in schizophrenia.This article aims to propose
      and support a concept of a triple brain network model of the dysfunctional
      switching between default mode and central executive network (CEN) related to the
      aberrant activity of the salience network. This model could represent a unitary
      mechanism of a wide array of symptom domains present in schizophrenia including
      the deficit of self (self-awareness and self-representation) and theory of mind
      (ToM) dysfunctions along with the traditional positive, negative and cognitive
      domains. We review previous studies which document the dysfunctions of self and
      ToM in schizophrenia together with neuroimaging data that support the triple
      brain network model as a common neuronal substrate of this dysfunction. 

PMID- 24910598
TI  - Anti-aggressive effects of neuropeptide S independent of anxiolysis in male rats.
AB  - Neuropeptide S (NPS) exerts robust anxiolytic and memory enhancing effects, but
      only in a non-social context. In order to study whether NPS affects aggressive
      behavior we used Wistar rats bred for low (LAB) and high (HAB) levels of innate
      anxiety-related behavior, respectively, which were both described to display
      increased levels of aggression compared with Wistar rats not selectively bred for
      anxiety (NAB). Male LAB, HAB, and NAB rats were tested for aggressive behavior
      toward a male intruder rat within their home cage (10 min, resident-intruder [RI]
      test). Intracerebroventricular (icv) infusion of NPS (1 nmol) significantly
      reduced inter-male aggression in LAB rats, and tended to reduce aggression in HAB
      and NAB males. However, local infusion of NPS (0.2 or 0.1 nmol NPS) into either
      the nucleus accumbens or the lateral hypothalamus did not influence aggressive
      behavior. Social investigation in the RI test and general social motivation
      assessed in the social preference paradigm were not altered by icv NPS (1 nmol).
      The anti-aggressive effect of NPS is most likely not causally linked to its
      anxiolytic properties, as intraperitoneal administration of the anxiogenic drug
      pentylenetetrazole decreased aggression in LAB rats whereas the anxiolytic drug
      diazepam did not affect aggression in HAB rats. Thus, although NPS has so far
      only been shown to exert effects on non-social behaviors, our results are the
      first demonstration of anti-aggressive effects of NPS in male rats. 

PMID- 24910599
TI  - Pre-reproductive maternal enrichment influences offspring developmental
      trajectories: motor behavior and neurotrophin expression.
AB  - Environmental enrichment is usually applied immediately after weaning or in
      adulthood, with strong effects on CNS anatomy and behavior. To examine the
      hypothesis that a pre-reproductive environmental enrichment of females could
      affect the motor development of their offspring, female rats were reared in an
      enriched environment from weaning to sexual maturity, while other female rats
      used as controls were reared under standard conditions. Following mating with
      standard-reared males, all females were housed individually. To evaluate the
      eventual transgenerational influence of positive pre-reproductive maternal
      experiences, postural and motor development of male pups was analyzed from birth
      to weaning. Moreover, expression of Brain Derived Neurotrophic Factor and Nerve
      Growth Factor in different brain regions was evaluated at birth and weaning. Pre
      reproductive environmental enrichment of females affected the offspring motor
      development, as indicated by the earlier acquisition of complex motor abilities
      displayed by the pups of enriched females. The earlier acquisition of motor
      abilities was associated with enhanced neurotrophin levels in striatum and
      cerebellum. In conclusion, maternal positive experiences were transgenerationally
      transmitted, and influenced offspring phenotype at both behavioral and
      biochemical levels. 

PMID- 24910601
TI  - Bursting thalamic responses in awake monkey contribute to visual detection and
      are modulated by corticofugal feedback.
AB  - The lateral geniculate nucleus is the gateway for visual information en route to
      the visual cortex. Neural activity is characterized by the existence of two
      firing modes: burst and tonic. Originally associated with sleep, bursts have now
      been postulated to be a part of the normal visual response, structured to
      increase the probability of cortical activation, able to act as a "wake-up" call
      to the cortex. We investigated a potential role for burst in the detection of
      novel stimuli by recording neuronal activity in the lateral geniculate nucleus
      (LGN) of behaving monkeys during a visual detection task. Our results show that
      bursts are often the neuron's first response, and are more numerous in the
      response to attended target stimuli than to unattended distractor stimuli. Bursts
      are indicators of the task novelty, as repetition decreased bursting. Because the
      primary visual cortex is the major modulatory input to the LGN, we compared the
      results obtained in control conditions with those observed when cortical activity
      was reduced by TMS. This cortical deactivation reduced visual response related
      bursting by 90%. These results highlight a novel role for the thalamus, able to
      code higher order image attributes as important as novelty early in the thalamo
      cortical conversation. 

PMID- 24910600
TI  - The role of dopamine in risk taking: a specific look at Parkinson's disease and
      gambling.
AB  - An influential model suggests that dopamine signals the difference between
      predicted and experienced reward. In this way, dopamine can act as a learning
      signal that can shape behaviors to maximize rewards and avoid punishments.
      Dopamine is also thought to invigorate reward seeking behavior. Loss of dopamine
      signaling is the major abnormality in Parkinson's disease. Dopamine agonists have
      been implicated in the occurrence of impulse control disorders in Parkinson's
      disease patients, the most common being pathological gambling, compulsive sexual
      behavior, and compulsive buying. Recently, a number of functional imaging studies
      investigating impulse control disorders in Parkinson's disease have been
      published. Here we review this literature, and attempt to place it within a
      decision-making framework in which potential gains and losses are evaluated to
      arrive at optimum choices. We also provide a hypothetical but still incomplete
      model on the effect of dopamine agonist treatment on these value and risk
      assessments. Two of the main brain structures thought to be involved in computing
      aspects of reward and loss are the ventral striatum (VStr) and the insula, both
      dopamine projection sites. Both structures are consistently implicated in
      functional brain imaging studies of pathological gambling in Parkinson's disease.

PMID- 24910604
TI  - Audiovisual correspondence between musical timbre and visual shapes.
AB  - This article investigates the cross-modal correspondences between musical timbre
      and shapes. Previously, such features as pitch, loudness, light intensity, visual
      size, and color characteristics have mostly been used in studies of audio-visual
      correspondences. Moreover, in most studies, simple stimuli e.g., simple tones
      have been utilized. In this experiment, 23 musical sounds varying in fundamental
      frequency and timbre but fixed in loudness were used. Each sound was presented
      once against colored shapes and once against grayscale shapes. Subjects had to
      select the visual equivalent of a given sound i.e., its shape, color (or
      grayscale) and vertical position. This scenario permitted studying the
      associations between normalized timbre and visual shapes as well as some of the
      previous findings for more complex stimuli. One hundred and nineteen subjects (31
      females and 88 males) participated in the online experiment. Subjects included 36
      claimed professional musicians, 47 claimed amateur musicians, and 36 claimed non
      musicians. Thirty-one subjects have also claimed to have synesthesia-like
      experiences. A strong association between timbre of envelope normalized sounds
      and visual shapes was observed. Subjects have strongly associated soft timbres
      with blue, green or light gray rounded shapes, harsh timbres with red, yellow or
      dark gray sharp angular shapes and timbres having elements of softness and
      harshness together with a mixture of the two previous shapes. Color or grayscale
      had no effect on timbre-shape associations. Fundamental frequency was not
      associated with height, grayscale or color. The significant correspondence
      between timbre and shape revealed by the present work allows designing
      substitution systems which might help the blind to perceive shapes through
      timbre. 

PMID- 24910602
TI  - Preclinical evidence supporting the clinical development of central pattern
      generator-modulating therapies for chronic spinal cord-injured patients.
AB  - Ambulation or walking is one of the main gaits of locomotion. In terrestrial
      animals, it may be defined as a series of rhythmic and bilaterally coordinated
      movement of the limbs which creates a forward movement of the body. This applies
      regardless of the number of limbs-from arthropods with six or more limbs to
      bipedal primates. These fundamental similarities among species may explain why
      comparable neural systems and cellular properties have been found, thus far, to
      control in similar ways locomotor rhythm generation in most animal models. The
      aim of this article is to provide a comprehensive review of the known structural
      and functional features associated with central nervous system (CNS) networks
      that are involved in the control of ambulation and other stereotyped motor
      patterns-specifically Central Pattern Generators (CPGs) that produce basic
      rhythmic patterned outputs for locomotion, micturition, ejaculation, and
      defecation. Although there is compelling evidence of their existence in humans,
      CPGs have been most studied in reduced models including in vitro isolated
      preparations, genetically-engineered mice and spinal cord-transected animals.
      Compared with other structures of the CNS, the spinal cord is generally
      considered as being well-preserved phylogenetically. As such, most animal models
      of spinal cord-injured (SCI) should be considered as valuable tools for the
      development of novel pharmacological strategies aimed at modulating spinal
      activity and restoring corresponding functions in chronic SCI patients. 

PMID- 24910605
TI  - What's so critical about Critical Neuroscience? Rethinking experiment, enacting
      critique.
AB  - In the midst of on-going hype about the power and potency of the new brain
      sciences, scholars within "Critical Neuroscience" have called for a more nuanced
      and sceptical neuroscientific knowledge-practice. Drawing especially on the
      Frankfurt School, they urge neuroscientists towards a more critical approach-one
      that re-inscribes the objects and practices of neuroscientific knowledge within
      webs of social, cultural, historical and political-economic contingency. This
      paper is an attempt to open up the black-box of "critique" within Critical
      Neuroscience itself. Specifically, we argue that limiting enactments of critique
      to the invocation of context misses the force of what a highly-stylized and
      tightly-bound neuroscientific experiment can actually do. We show that, within
      the neuroscientific experiment itself, the world-excluding and context-denying
      "rules of the game" may also enact critique, in novel and surprising forms, while
      remaining formally independent of the workings of society, and culture, and
      history. To demonstrate this possibility, we analyze the Optimally Interacting
      Minds (OIM) paradigm, a neuroscientific experiment that used classical
      psychophysical methods to show that, in some situations, people worked better as
      a collective, and not as individuals-a claim that works precisely against
      reactionary tendencies that prioritize individual over collective agency, but
      that was generated and legitimized entirely within the formal, context-denying
      conventions of neuroscientific experimentation. At the heart of this paper is a
      claim that it was precisely the rigors and rules of the experimental game that
      allowed these scientists to enact some surprisingly critical, and even radical,
      gestures. We conclude by suggesting that, in the midst of large-scale
      neuroscientific initiatives, it may be "experiment", and not "context", that
      forms the meeting-ground between neuro-biological and socio-political research
      practices. 

PMID- 24910603
TI  - Neuroanatomical substrates of action perception and understanding: an anatomic
      likelihood estimation meta-analysis of lesion-symptom mapping studies in brain
      injured patients.
AB  - Several neurophysiologic and neuroimaging studies suggested that motor and
      perceptual systems are tightly linked along a continuum rather than providing
      segregated mechanisms supporting different functions. Using correlational
      approaches, these studies demonstrated that action observation activates not only
      visual but also motor brain regions. On the other hand, brain stimulation and
      brain lesion evidence allows tackling the critical question of whether our action
      representations are necessary to perceive and understand others' actions. In
      particular, recent neuropsychological studies have shown that patients with
      temporal, parietal, and frontal lesions exhibit a number of possible deficits in
      the visual perception and the understanding of others' actions. The specific
      anatomical substrates of such neuropsychological deficits however, are still a
      matter of debate. Here we review the existing literature on this issue and
      perform an anatomic likelihood estimation meta-analysis of studies using lesion
      symptom mapping methods on the causal relation between brain lesions and non
      linguistic action perception and understanding deficits. The meta-analysis
      encompassed data from 361 patients tested in 11 studies and identified regions in
      the inferior frontal cortex, the inferior parietal cortex and the middle/superior
      temporal cortex, whose damage is consistently associated with poor performance in
      action perception and understanding tasks across studies. Interestingly, these
      areas correspond to the three nodes of the action observation network that are
      strongly activated in response to visual action perception in neuroimaging
      research and that have been targeted in previous brain stimulation studies. Thus,
      brain lesion mapping research provides converging causal evidence that premotor,
      parietal and temporal regions play a crucial role in action recognition and
      understanding. 

PMID- 24910606
TI  - Injury of the cingulum in patients with putaminal hemorrhage: a diffusion tensor
      tractography study.
AB  - OBJECTIVES: Little is known about the pathophysiological mechanisms of cognitive
      impairment in patients with putaminal hemorrhage (PH). Using diffusion tensor
      tractography, we investigated injury of the cingulum in patients with PH.
      METHODS: We recruited 63 patients with PH, who were classified according to three
      groups, based on integrity of the cingulum to the lower portion of the genu of
      the corpus callosum: group A; preserved integrity, group B; discontinuation of
      integrity in the affected hemisphere, and group C; discontinuation of integrity
      in both hemispheres. RESULTS: Thirty four patients (54.0%) belonged to group A,
      16 patients (25.4%) to group B, and the remaining 13 patients (20.6%) to group C.
      Regarding the Mini-Mental State Examination, significant differences were
      observed between group A and group C, and between group B and group C without
      significant difference between group A and group B (p < 0.05). In terms of the
      volume of hematoma, significant differences were observed among the three groups
      (p < 0.05). Regarding the most anterior point of the hematoma, significant
      differences were observed between group A and groups B and C (p < 0.05); in
      contrast, regarding the most point of hematoma, significant differences were
      observed between group C and groups A and B, respectively (p < 0.05). CONCLUSION:
      We found that the anterior cingulum is vulnerable to PH. Therefore, our results
      suggest the necessity for evaluation of the cingulum in patients with PH
      particularly if the hematoma is large or close to the anterior margin or midline
      of the brain.

PMID- 24910607
TI  - Somatosensory inputs by application of KinesioTaping: effects on spasticity,
      balance, and gait in chronic spinal cord injury.
AB  - INTRODUCTION: Leg paralysis, spasticity, reduced interlimb coordination, and
      impaired balance are the chief limitations to overground ambulation in subjects
      with incomplete spinal cord injury (SCI). In recent years, the application of
      KinesioTaping (KT) has been proposed to enhance sensory inputs, decreasing
      spasticity by proprioception feedback and relieving abnormal muscle tension.
      Because no studies have examined KT-based techniques in SCI subjects, our goal
      was to analyze the effects of ankle joint KT on spasticity, balance, and gait.
      MATERIALS AND METHODS: A randomized crossover case control design was used to
      compare the effects of KT and conventional nonelastic silk tape (ST) in 11
      chronic SCI subjects, AIS level D, with soleus/gastrocnemius (S/G) muscle
      spasticity and balance and gait impairments. TREATMENT: 48 h of treatment with KT
      or ST was followed by 48 h with the other technique after 1 week. A single Y
      strip of Cure((c)) tape (KT) and ST was to the S and G muscles with 0% stretch.
      Before and 48 h after of application of KT and ST, clinical data on the range of
      motion (ROM), spasticity, clonus, pain, balance, and gait were collected.
      Stabilometric platform assessment of center of pressure (COP) movements;
      bidimensional gait analysis; and recording of electromyographic (EMG) activity of
      the S, G, and tibialis anterior and extensor hallucis lungus muscles were also
      performed. RESULTS: Only KT had significant effects on spasticity (p < 0.05),
      clonus (p < 0.001) and COP movements (p < 0.05), kinematic gait parameters (p <
      0.001), and EMG activity (p < 0.001). Comparison between ST and KT improvements
      pointed out significant differences as concerns ROM (p < 0.001), spasticity (p <
      0.001), clonus (p < 0.001), pain (p < 0.001), COP parameters (p < 0.05), and most
      kinematic gait data (p < 0.05). DISCUSSION: Short-term application of KT reduces
      spasticity and pain and improves balance and gait in chronic SCI subjects.
      Although these data are promising, they require confirmation in a larger cohort
      of patients.

PMID- 24910608
TI  - Afterhyperpolarization of human motoneurons firing double and triple discharges.

PMID- 24910609
TI  - Canonical information flow decomposition among neural structure subsets.
AB  - Partial directed coherence (PDC) and directed coherence (DC) which describe
      complementary aspects of the directed information flow between pairs of
      univariate components that belong to a vector of simultaneously observed time
      series have recently been generalized as bPDC/bDC, respectively, to portray the
      relationship between subsets of component vectors (Takahashi, 2009; Faes and
      Nollo, 2013). This generalization is specially important for neuroscience
      applications as one often wishes to address the link between the set of time
      series from an observed ROI (region of interest) with respect to series from some
      other physiologically relevant ROI. bPDC/bDC are limited, however, in that
      several time series within a given subset may be irrelevant or may even interact
      opposingly with respect to one another leading to interpretation difficulties. To
      address this, we propose an alternative measure, termed cPDC/cDC, employing
      canonical decomposition to reveal the main frequency domain modes of interaction
      between the vector subsets. We also show bPDC/bDC and cPDC/cDC are related and
      possess mutual information rate interpretations. Numerical examples and a real
      data set illustrate the concepts. The present contribution provides what is
      seemingly the first canonical decomposition of information flow in the frequency
      domain. 

PMID- 24910610
TI  - Real-time multi-peak tractography for instantaneous connectivity display.
AB  - The computerized process of reconstructing white matter tracts from diffusion MRI
      (dMRI) data is often referred to as tractography. Tractography is nowadays
      central in structural connectivity since it is the only non-invasive technique to
      obtain information about brain wiring. Most publicly available tractography
      techniques and most studies are based on a fixed set of tractography parameters.
      However, the scale and curvature of fiber bundles can vary from region to region
      in the brain. Therefore, depending on the area of interest or subject (e.g.,
      healthy control vs. tumor patient), optimal tracking parameters can be
      dramatically different. As a result, a slight change in tracking parameters may
      return different connectivity profiles and complicate the interpretation of the
      results. Having access to tractography parameters can thus be advantageous, as it
      will help in better isolating those which are sensitive to certain streamline
      features and potentially converge on optimal settings which are area-specific. In
      this work, we propose a real-time fiber tracking (RTT) tool which can
      instantaneously compute and display streamlines. To achieve such real-time
      performance, we propose a novel evolution equation based on the upsampled
      principal directions, also called peaks, extracted at each voxel of the dMRI
      dataset. The technique runs on a single Computer Processing Unit (CPU) without
      the need for Graphical Unit Processing (GPU) programming. We qualitatively
      illustrate and quantitatively evaluate our novel multi-peak RTT technique on
      phantom and human datasets in comparison with the state of the art offline
      tractography from MRtrix, which is robust to fiber crossings. Finally, we show
      how our RTT tool facilitates neurosurgical planning and allows one to find fibers
      that infiltrate tumor areas, otherwise missing when using the standard default
      tracking parameters. 

PMID- 24910611
TI  - Cell-type specific mechanisms of D-serine uptake and release in the brain.
AB  - Accumulating evidence during the last decade established that D-serine is a key
      signaling molecule utilized by neurons and astroglia in the mammalian central
      nervous system. D-serine is increasingly appreciated as the main physiological
      endogenous coagonist for synaptic NMDA receptors at central excitatory synapses;
      it is mandatory for long-term changes in synaptic strength, memory, learning, and
      social interactions. Alterations in the extracellular levels of D-serine leading
      to disrupted cell-cell signaling are a trademark of many chronic or acute
      neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e.,
      schizophrenia) disorders, and are associated with addictive behavior (i.e.,
      cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine,
      achieved by various molecular machineries and signaling pathways, is necessary
      for maintenance of accurate NMDA receptor functions. Here, we review the
      experimental data supporting the notion that astroglia and neurons use different
      pathways to regulate levels of extracellular D-serine. 

PMID- 24910612
TI  - Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in
      3xTg-AD mice.
AB  - BACKGROUND: It is well documented that elderly individuals are at increased risk
      of cognitive decline after anesthesia. General anesthesia is believed to be a
      risk factor for Alzheimer's disease (AD). Recent studies suggest that anesthesia
      may increase the risk for cognitive decline and AD through promoting abnormal
      hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD.
      METHODS: We treated 3xTg-AD mice, a commonly used transgenic mouse model of AD,
      with daily intranasal administration of insulin (1.75 U/day) for one week. The
      insulin- and control-treated mice were then anesthetized with single
      intraperitoneal injection of propofol (250 mg/kg body weight). Tau
      phosphorylation and tau protein kinases and phosphatases in the brains of mice 30
      min and 2 h after propofol injection were then investigated by using Western
      blots and immunohistochemistry. RESULTS: Propofol strongly promoted
      hyperphosphorylation of tau at several AD-related phosphorylation sites.
      Intranasal administration of insulin attenuated propofol-induced
      hyperphosphorylation of tau, promoted brain insulin signaling, and led to up
      regulation of protein phosphatase 2A, a major tau phosphatase in the brain.
      Intranasal insulin also resulted in down-regulation of several tau protein
      kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin
      dependent protein kinase II, and c-Jun N-terminal kinase. CONCLUSION: Our results
      demonstrate that pretreatment with intranasal insulin prevents AD-like tau
      hyperphosphorylation. These findings provide the first evidence supporting that
      intranasal insulin administration might be used for the prevention of anesthesia
      induced cognitive decline and increased risk for AD and dementia.

PMID- 24910613
TI  - Aging Influence on Gray Matter Structural Associations within the Default Mode
      Network Utilizing Bayesian Network Modeling.
AB  - Recent neuroimaging studies have revealed normal aging-related alterations in
      functional and structural brain networks such as the default mode network (DMN).
      However, less is understood about specific brain structural dependencies or
      interactions between brain regions within the DMN in the normal aging process. In
      this study, using Bayesian network (BN) modeling, we analyzed gray matter volume
      data from 109 young and 82 old subjects to characterize the influence of aging on
      associations between core brain regions within the DMN. Furthermore, we
      investigated the discriminability of the aging-associated BN models for the young
      and old groups. Compared to their young counterparts, the old subjects showed
      significant reductions in connections from right inferior temporal cortex (ITC)
      to medial prefrontal cortex (mPFC), right hippocampus (HP) to right ITC, and mPFC
      to posterior cingulate cortex and increases in connections from left HP to mPFC
      and right inferior parietal cortex to right ITC. Moreover, the classification
      results showed that the aging-related BN models could predict group membership
      with 88.48% accuracy, 88.07% sensitivity, and 89.02% specificity. Our findings
      suggest that structural associations within the DMN may be affected by normal
      aging and provide crucial information about aging effects on brain structural
      networks. 

PMID- 24910615
TI  - PDE7B is involved in nandrolone decanoate hydrolysis in liver cytosol and its
      transcription is up-regulated by androgens in HepG2.
AB  - Most androgenic drugs are available as esters for a prolonged depot action.
      However, the enzymes involved in the hydrolysis of the esters have not been
      identified. There is one study indicating that PDE7B may be involved in the
      activation of testosterone enanthate. The aims are to identify the cellular
      compartments where the hydrolysis of testosterone enanthate and nandrolone
      decanoate occurs, and to investigate the involvement of PDE7B in the activation.
      We also determined if testosterone and nandrolone affect the expression of the
      PDE7B gene. The hydrolysis studies were performed in isolated human liver
      cytosolic and microsomal preparations with and without specific PDE7B inhibitor.
      The gene expression was studied in human hepatoma cells (HepG2) exposed to
      testosterone and nandrolone. We show that PDE7B serves as a catalyst of the
      hydrolysis of testosterone enanthate and nandrolone decanoate in liver cytosol.
      The gene expression of PDE7B was significantly induced 3- and 5- fold after 2 h
      exposure to 1 MUM testosterone enanthate and nandrolone decanoate, respectively.
      These results show that PDE7B is involved in the activation of esterified
      nandrolone and testosterone and that the gene expression of PDE7B is induced by
      supra-physiological concentrations of androgenic drugs. 

PMID- 24910614
TI  - Iron, anemia and hepcidin in malaria.
AB  - Malaria and iron have a complex but important relationship. Plasmodium
      proliferation requires iron, both during the clinically silent liver stage of
      growth and in the disease-associated phase of erythrocyte infection. Precisely
      how the protozoan acquires its iron from its mammalian host remains unclear, but
      iron chelators can inhibit pathogen growth in vitro and in animal models. In
      humans, iron deficiency appears to protect against severe malaria, while iron
      supplementation increases risks of infection and disease. Malaria itself causes
      profound disturbances in physiological iron distribution and utilization, through
      mechanisms that include hemolysis, release of heme, dyserythropoiesis, anemia,
      deposition of iron in macrophages, and inhibition of dietary iron absorption.
      These effects have significant consequences. Malarial anemia is a major global
      health problem, especially in children, that remains incompletely understood and
      is not straightforward to treat. Furthermore, the changes in iron metabolism
      during a malaria infection may modulate susceptibility to co-infections. The
      release of heme and accumulation of iron in granulocytes may explain increased
      vulnerability to non-typhoidal Salmonella during malaria. The redistribution of
      iron away from hepatocytes and into macrophages may confer host resistance to
      superinfection, whereby blood-stage parasitemia prevents the development of a
      second liver-stage Plasmodium infection in the same organism. Key to
      understanding the pathophysiology of iron metabolism in malaria is the activity
      of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood
      stage parasitemia and likely mediates much of the iron redistribution that
      accompanies disease. Understanding the regulation and role of hepcidin may offer
      new opportunities to combat malaria and formulate better approaches to treat
      anemia in the developing world. 

PMID- 24910616
TI  - Origins and consequences of hyperosmolar stress in retinal pigmented epithelial
      cells.
AB  - The retinal pigmented epithelium (RPE) is composed of retinal pigmented
      epithelial cells joined by tight junctions and represents the outer blood-retinal
      barrier (BRB). The inner BRB is made of endothelial cells joined by tight
      junctions and glial extensions surrounding all the retinal blood vessels. One of
      the functions of the RPE is to maintain an osmotic transepithelial gradient
      created by ionic pumps and channels, avoiding paracellular flux. Under such
      physiological conditions, transcellular water movement follows the osmotic
      gradient and flows normally from the retina to the choroid through the RPE.
      Several diseases, such as diabetic retinopathy, are characterized by the BRB
      breakdown leading to leakage of solutes, proteins, and fluid from the retina and
      the choroid. The prevailing hypothesis explaining macular edema formation during
      diabetic retinopathy incriminates the inner BRB breakdown resulting in increased
      osmotic pressure leading in turn to massive water accumulation that can affect
      vision. Under these conditions, it has been hypothesized that RPE is likely to be
      exposed to hyperosmolar stress at its apical side. This review summarizes the
      origins and consequences of osmotic stress in the RPE. Ongoing and further
      research advances will clarify the mechanisms, at the molecular level, involved
      in the response of the RPE to osmotic stress and delineate potential novel
      therapeutic targets and tools. 

PMID- 24910618
TI  - 3D hydrogel environment rejuvenates aged pericytes for skeletal muscle tissue
      engineering.
AB  - Skeletal muscle tissue engineering is a promising approach for the treatment of
      muscular disorders. However, the complex organization of muscle, combined with
      the difficulty in finding an appropriate source of regenerative cells and in
      providing an adequate blood supply to the engineered tissue, makes this a hard
      task to face. In the present work, we describe an innovative approach to
      rejuvenate adult skeletal muscle-derived pericytes (MP) based on the use of a PEG
      based hydrogel scaffold. MP were isolated from young (piglet) and adult (boar)
      pigs to assess whether aging affects tissue regeneration efficiency. In vitro, MP
      from boars had similar morphology and colony forming capacity to piglet MP, but
      an impaired ability to form myotubes and capillary-like structures. However, the
      use of a PEG-based hydrogel to support adult MP significantly improved their
      myogenic differentiation and angiogenic potentials in vitro and in vivo. Thus,
      PEG-based hydrogel scaffolds may provide a progenitor cell "niche" that promotes
      skeletal muscle regeneration and blood vessel growth, and together with pericytes
      may be developed for use in regenerative applications. 

PMID- 24910617
TI  - Beyond cellular detoxification: a plethora of physiological roles for MDR
      transporter homologs in plants.
AB  - Higher plants possess a multitude of Multiple Drug Resistance (MDR) transporter
      homologs that group into three distinct and ubiquitous families-the ATP-Binding
      Cassette (ABC) superfamily, the Major Facilitator Superfamily (MFS), and the
      Multidrug And Toxic compound Extrusion (MATE) family. As in other organisms, such
      as fungi, mammals, and bacteria, MDR transporters make a primary contribution to
      cellular detoxification processes in plants, mainly through the extrusion of
      toxic compounds from the cell or their sequestration in the central vacuole. This
      review aims at summarizing the currently available information on the in vivo
      roles of MDR transporters in plant systems. Taken together, these data clearly
      indicate that the biological functions of ABC, MFS, and MATE carriers are not
      restricted to xenobiotic and metal detoxification. Importantly, the activity of
      plant MDR transporters also mediates biotic stress resistance and is instrumental
      in numerous physiological processes essential for optimal plant growth and
      development, including the regulation of ion homeostasis and polar transport of
      the phytohormone auxin. 

PMID- 24910620
TI  - Time computations in anuran auditory systems.
AB  - Temporal computations are important in the acoustic communication of anurans. In
      many cases, calls between closely related species are nearly identical spectrally
      but differ markedly in temporal structure. Depending on the species, calls can
      differ in pulse duration, shape and/or rate (i.e., amplitude modulation),
      direction and rate of frequency modulation, and overall call duration. Also,
      behavioral studies have shown that anurans are able to discriminate between calls
      that differ in temporal structure. In the peripheral auditory system, temporal
      information is coded primarily in the spatiotemporal patterns of activity of
      auditory-nerve fibers. However, major transformations in the representation of
      temporal information occur in the central auditory system. In this review I
      summarize recent advances in understanding how temporal information is
      represented in the anuran midbrain, with particular emphasis on mechanisms that
      underlie selectivity for pulse duration and pulse rate (i.e., intervals between
      onsets of successive pulses). Two types of neurons have been identified that show
      selectivity for pulse rate: long-interval cells respond well to slow pulse rates
      but fail to spike or respond phasically to fast pulse rates; conversely, interval
      counting neurons respond to intermediate or fast pulse rates, but only after a
      threshold number of pulses, presented at optimal intervals, have occurred.
      Duration-selectivity is manifest as short-pass, band-pass or long-pass tuning.
      Whole-cell patch recordings, in vivo, suggest that excitation and inhibition are
      integrated in diverse ways to generate temporal selectivity. In many cases,
      activity-related enhancement or depression of excitatory or inhibitory processes
      appear to contribute to selective responses. 

PMID- 24910619
TI  - Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett
      syndrome: therapeutic perspectives for 5-HT1A agonists.
AB  - Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG
      binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional
      regulator has a devastating effect on the central nervous system. One of the most
      severe and life-threatening presentations of this syndrome is brainstem
      dysfunction, which results in autonomic disturbances such as breathing deficits,
      typified by episodes of breathing cessation intercalated with episodes of
      hyperventilation or irregular breathing. Defects in numerous neurotransmitter
      systems have been observed in Rett syndrome both in animal models and patients.
      Here we dedicate special attention to serotonin due to its role in promoting
      regular breathing, increasing vagal tone, regulating mood, alleviating
      Parkinsonian-like symptoms and potential for therapeutic translation. A promising
      new symptomatic strategy currently focuses on regulation of serotonergic function
      using highly selective serotonin type 1A (5-HT1A) "biased agonists." We address
      this newly emerging therapy for respiratory brainstem dysfunction and challenges
      for translation with a holistic perspective of Rett syndrome, considering
      potential mood and motor effects. 

PMID- 24910621
TI  - Music evokes vicarious emotions in listeners.
AB  - Why do we listen to sad music? We seek to answer this question using a
      psychological approach. It is possible to distinguish perceived emotions from
      those that are experienced. Therefore, we hypothesized that, although sad music
      is perceived as sad, listeners actually feel (experience) pleasant emotions
      concurrent with sadness. This hypothesis was supported, which led us to question
      whether sadness in the context of art is truly an unpleasant emotion. While
      experiencing sadness may be unpleasant, it may also be somewhat pleasant when
      experienced in the context of art, for example, when listening to sad music. We
      consider musically evoked emotion vicarious, as we are not threatened when we
      experience it, in the way that we can be during the course of experiencing
      emotion in daily life. When we listen to sad music, we experience vicarious
      sadness. In this review, we propose two sides to sadness by suggesting vicarious
      emotion. 

PMID- 24910622
TI  - Use what you can: storage, abstraction processes, and perceptual adjustments help
      listeners recognize reduced forms.
AB  - Three eye-tracking experiments tested whether native listeners recognized reduced
      Dutch words better after having heard the same reduced words, or different
      reduced words of the same reduction type and whether familiarization with one
      reduction type helps listeners to deal with another reduction type. In the
      exposure phase, a segmental reduction group was exposed to /b/-reductions (e.g.,
      minderij instead of binderij, "book binder") and a syllabic reduction group was
      exposed to full-vowel deletions (e.g., p'raat instead of paraat, "ready"), while
      a control group did not hear any reductions. In the test phase, all three groups
      heard the same speaker producing reduced-/b/ and deleted-vowel words that were
      either repeated (Experiments 1 and 2) or new (Experiment 3), but that now
      appeared as targets in semantically neutral sentences. Word-specific learning
      effects were found for vowel-deletions but not for /b/-reductions. Generalization
      of learning to new words of the same reduction type occurred only if the exposure
      words showed a phonologically consistent reduction pattern (/b/-reductions). In
      contrast, generalization of learning to words of another reduction type occurred
      only if the exposure words showed a phonologically inconsistent reduction pattern
      (the vowel deletions; learning about them generalized to recognition of the /b/
      reductions). In order to deal with reductions, listeners thus use various means.
      They store reduced variants (e.g., for the inconsistent vowel-deleted words) and
      they abstract over incoming information to build up and apply mapping rules
      (e.g., for the consistent /b/-reductions). Experience with inconsistent
      pronunciations leads to greater perceptual flexibility in dealing with other
      forms of reduction uttered by the same speaker than experience with consistent
      pronunciations. 

PMID- 24910623
TI  - An enactive and dynamical systems theory account of dyadic relationships.
AB  - Many social relationships are a locus of struggle and suffering, either at the
      individual or interactional level. In this paper we explore why this is the case
      and suggest a modeling approach for dyadic interactions and the well-being of the
      participants. To this end we bring together an enactive approach to self with
      dynamical systems theory. Our basic assumption is that the quality of any social
      interaction or relationship fundamentally depends on the nature and constitution
      of the individuals engaged in these interactions. From an enactive perspective
      the self is conceived as an embodied and socially enacted autonomous system
      striving to maintain an identity. This striving involves a basic two-fold goal:
      the ability to exist as an individual in one's own right, while also being open
      to and affected by others. In terms of dynamical systems theory one can thus
      consider the individual self as a self-other organized system represented by a
      phase space spanned by the dimensions of distinction and participation, where
      attractors can be defined. Based on two everyday examples of dyadic relationship
      we propose a simple model of relationship dynamics, in which struggle or well
      being in the dyad is analyzed in terms of movements of dyadic states that are in
      tension or in harmony with individually developed attractors. Our model predicts
      that relationships can be sustained when the dyad develops a new joint attractor
      toward which dyadic states tend to move, and well-being when this attractor is in
      balance with the individuals' attractors. We outline how this can inspire
      research on psychotherapy. The psychotherapy process itself provides a setting
      that supports clients to become aware how they fare with regards to the two-fold
      norm of distinction and participation and develop, through active engagement
      between client (or couple) and therapist, strategies to co-negotiate their self
      organization. 

PMID- 24910624
TI  - Tool use imagery triggers tool incorporation in the body schema.
AB  - Tool-use has been shown to modify the way the brain represents the metrical
      characteristics of the effector controlling the tool. For example, the use of
      tools that elongate the physical length of the arm induces kinematic changes
      affecting selectively the transport component of subsequent free-hand movements.
      Although mental simulation of an action is known to involve -to a large extent-
      the same processes as those at play in overt motor execution, whether tool-use
      imagery can yield similar effects on the body representation remains unknown.
      Mentally simulated actions indeed elicit autonomic physiological responses and
      follow motor execution rules that are comparable to those associated with the
      correspondent overt performance. Therefore, here we investigated the effects of
      the mental simulation of actions performed with a tool on the body representation
      by studying subsequent free-hand movements. Subjects executed reach to grasp
      movements with their hand before and after an imagery task performed with either
      a tool elongating their arm length or, as a control, with their hand alone. Two
      main results were found: First, in agreement with previous studies, durations of
      imagined movements performed with the tool and the hand were similarly affected
      by task difficulty. Second, kinematics of free-hand movements was affected after
      tool-use imagery, but not hand-use imagery, in a way similar to that previously
      documented after actual tool-use. These findings constitute the first evidence
      that tool-use imagery is sufficient to affect the representation of the user's
      arm. 

PMID- 24910625
TI  - Family routines within the ecological niche: an analysis of the psychological
      well-being of U.S. caregivers of children with disabilities.
AB  - Using mixed methods, this study examined the relationship of caregivers of
      children with disabilities' psychological well-being (PWB) and their
      orchestration of daily routines within their ecological niche. Thirty-nine U.S.
      caregivers completed in-depth interviews, PWB Scales, and Family Time and
      Routines Index (FTRI). We used a multi-step analysis. Interview data was coded
      and vignettes created without knowledge of PWB and FTRI ratings. Next, the
      relationship of quantitative measures was analyzed. Four groups were created
      using FTRI-extent and PWB means: (1) low routine-low PWB, (2) low routine-high
      PWB, (3) high routine-low PWB, and (4) high routine-high PWB. We examined
      qualitative differences in key features between groups. FINDINGS: Total PWB and
      FTRI scores were not significantly correlated, PWB Purpose in Life and FTRI
      extent scores were moderately positively correlated, and PWB Environmental
      Mastery and FTRI-extent correlation approached significance. Qualitative findings
      describe caregivers' structuring of routines, intensity of oversight, support in
      routines, management of dinner, paid work, and needs for respite. The four groups
      differed in paid work, household support, degree the child could self-occupy,
      Environmental Mastery, and opportunities to recuperate. Caregivers with higher
      levels of well-being and more regular routines did paid work, had supportive
      spouses, had children who more often could follow routines, had higher
      Environmental Mastery, could orchestrate a family meal, and had breaks from care
      in either work or leisure. All Native American caregivers and Mexican American
      caregivers with spouses were in the high routine-high PWB group. Insight into
      this complex negotiation between family members within daily routines may provide
      practitioners a better understanding of how to work within family circles to
      foster therapeutic alliances, identify focused intervention targets, and promote
      positive family wide outcomes.

PMID- 24910627
TI  - From features to dimensions: cognitive and motor development in pop-out search in
      children and young adults.
AB  - In an experiment involving a total of 124 participants, divided into eight age
      groups (6-, 8-, 10-, 12-, 14-, 16-, 18-, and 20-year-olds) the development of the
      processing components underlying visual search for pop-out targets was tracked.
      Participants indicated the presence or absence of color or orientation feature
      singleton targets. Observers also solved a detection task, in which they
      responded to the onset of search arrays. There were two main results. First,
      analyses of inter-trial effects revealed differences in the search strategies of
      the 6-year-old participants compared to older age groups. Participants older than
      8 years based target detection on feature-less dimensional salience signals
      (indicated by cross-trial RT costs in target dimension change relative to
      repetition trials), the 6-year-olds accessed the target feature to make a target
      present or absent decision (cross-trial RT costs in target feature change
      relative to feature repetition trials). The result agrees with predictions
      derived from the Dimension Weighting account and previous investigations of inter
      trial effects in adult observers (Muller et al., 1995; Found and Muller, 1996).
      The results are also in line with theories of cognitive development suggesting
      that the ability to abstract specific visual features into feature categories is
      developed after the age of 7 years. Second, overall search RTs decreased with
      increasing age in a decelerated fashion. RT differences between consecutive age
      groups can be explained by sensory-motor maturation up to the age of 10 years (as
      indicated by RTs in the onset detection task). Expedited RTs in older age groups
      (10-, vs. 12-year-olds; 14- vs. 16-year-olds), but also in the 6- vs. 8-year
      olds, are due to the development of search-related (cognitive) processes.
      Overall, the results suggest that the level of adult performance in visual search
      for pop-out targets is achieved by the age of 16. 

PMID- 24910626
TI  - Acute psychosocial stress and emotion regulation skills modulate empathic
      reactions to pain in others.
AB  - Psychosocial stress affects resources for adequate coping with environmental
      demands. A crucial question in this context is the extent to which acute
      psychosocial stressors impact empathy and emotion regulation. In the present
      study, 120 participants were randomly assigned to a control group vs. a group
      confronted with the Trier Social Stress Test (TSST), an established paradigm for
      the induction of acute psychosocial stress. Empathy for pain as a specific
      subgroup of empathy was assessed via pain intensity ratings during a pain-picture
      task. Self-reported emotion regulation skills were measured as predictors using
      an established questionnaire. Stressed individuals scored significantly lower on
      the appraisal of pain pictures. A regression model was chosen to find variables
      that further predict the pain ratings. These findings implicate that acute
      psychosocial stress might impair empathic processes to observed pain in another
      person and the ability to accept one's emotion additionally predicts the empathic
      reaction. Furthermore, the ability to tolerate negative emotions modulated the
      relation between stress and pain judgments, and thus influenced core cognitive
      affective functions relevant for coping with environmental challenges. In
      conclusion, our study emphasizes the necessity of reducing negative emotions in
      terms of empathic distress when confronted with pain of another person under
      psychosocial stress, in order to be able to retain pro-social behavior. 

PMID- 24910629
TI  - Development of reference assignment in children: a direct comparison to the
      performance of cognitive shift.
AB  - The referent of a deictic embedded in a particular utterance or sentence is often
      ambiguous. Reference assignment is a pragmatic process that enables the
      disambiguation of such a referent. Previous studies have demonstrated that
      receivers use social-pragmatic information during referent assignment; however,
      it is still unclear which aspects of cognitive development affect the development
      of referential processing in children. The present study directly assessed the
      relationship between performance on a reference assignment task (Murakami and
      Hashiya, in preparation) and the dimensional change card sort task (DCCS) in 3-
      and 5-years-old children. The results indicated that the 3-years-old children who
      passed DCCS showed performance above chance level in the event which required an
      explicit (cognitive) shift, while the performance of the children who failed DCCS
      remained in the range of chance level; however, such a tendency was not observed
      in the 5-years-old, possibly due to a ceiling effect. The results indicated that,
      though the development of skills that mediate cognitive shifting might adequately
      explain the explicit shift of attention in conversation, the pragmatic processes
      underlying the implicit shift, which requires reference assignment, might follow
      a different developmental course. 

PMID- 24910628
TI  - The roles of scene priming and location priming in object-scene consistency
      effects.
AB  - Presenting consistent objects in scenes facilitates object recognition as
      compared to inconsistent objects. Yet the mechanisms by which scenes influence
      object recognition are still not understood. According to one theory, consistent
      scenes facilitate visual search for objects at expected places. Here, we
      investigated two predictions following from this theory: If visual search is
      responsible for consistency effects, consistency effects could be weaker (1) with
      better-primed than less-primed object locations, and (2) with less-primed than
      better-primed scenes. In Experiments 1 and 2, locations of objects were varied
      within a scene to a different degree (one, two, or four possible locations). In
      addition, object-scene consistency was studied as a function of progressive
      numbers of repetitions of the backgrounds. Because repeating locations and
      backgrounds could facilitate visual search for objects, these repetitions might
      alter the object-scene consistency effect by lowering of location uncertainty.
      Although we find evidence for a significant consistency effect, we find no clear
      support for impacts of scene priming or location priming on the size of the
      consistency effect. Additionally, we find evidence that the consistency effect is
      dependent on the eccentricity of the target objects. These results point to only
      small influences of priming to object-scene consistency effects but all-in-all
      the findings can be reconciled with a visual-search explanation of the
      consistency effect. 

PMID- 24910630
TI  - Liking and wanting pleasant odors: different effects of repetitive exposure in
      men and women.
AB  - Odors can enrich the perception of our environment and are commonly used to
      attract people in marketing situations. However, the perception of an odor
      changes over repetitions. This study investigated whether repetitive exposition
      to olfactory stimuli leads to a change in the perceived pleasantness ("liking")
      or in the wish to be further exposed to the same olfactory stimulus ("wanting"),
      and whether these two mechanisms show gender differences. Three different
      pleasant odors were each repeatedly presented for 40 times in random order with a
      mean inter-stimulus interval of 18 s. Eighteen participants rated both "liking"
      and "wanting" for each of the 120 olfactory stimuli. Wanting ratings decreased
      significantly over repetitions in women and men, with a steeper decrease for men
      during the initial trials before plateauing. In contrast, liking ratings
      decreased significantly over repetitions only in men, with a steeper decrease
      after the initial ratings, but not in women. Additionally, women scored higher in
      a questionnaire on reward responsiveness than men. We conclude that positive
      evaluation (liking) and the wish to experience more of the same (wanting) are
      different concepts even in the domain of olfaction. The persistence of perceived
      pleasantness in women may be due to the attribution of a greater subjective value
      to odors. 

PMID- 24910631
TI  - Thyroid hormone action: astrocyte-neuron communication.
AB  - Thyroid hormone (TH) action is exerted mainly through regulation of gene
      expression by binding of T3 to the nuclear receptors. T4 plays an important role
      as a source of intracellular T3 in the central nervous system via the action of
      the type 2 deiodinase (D2), expressed in the astrocytes. A model of T3
      availability to neural cells has been proposed and validated. The model
      contemplates that brain T3 has a double origin: a fraction is available directly
      from the circulation, and another is produced locally from T4 in the astrocytes
      by D2. The fetal brain depends almost entirely on the T3 generated locally. The
      contribution of systemic T3 increases subsequently during development to account
      for approximately 50% of total brain T3 in the late postnatal and adult stages.
      In this article, we review the experimental data in support of this model, and
      how the factors affecting T3 availability in the brain, such as deiodinases and
      transporters, play a decisive role in modulating local TH action during
      development. 

PMID- 24910632
TI  - Interactions of proteins with biogenic iron oxyhydroxides and a new culturing
      technique to increase biomass yields of neutrophilic, iron-oxidizing bacteria.
AB  - Neutrophilic, bacterial iron-oxidation remains one of the least understood energy
      generating biological reactions to date. One of the reasons it remains under
      studied is because there are inherent problems with working with iron-oxidizing
      bacteria (FeOB), including low biomass yields and interference from the iron
      oxides in the samples. In an effort to circumvent the problem of low biomass, a
      new large batch culturing technique was developed. Protein interactions with
      biogenic iron oxides were investigated confirming that such interactions are
      strong. Therefore, a protein extraction method is described to minimize binding
      of proteins to biogenic iron oxides. The combination of these two methods results
      in protein yields that are appropriate for activity assays in gels and for
      proteomic profiling. 

PMID- 24910633
TI  - A snapshot of extracellular DNA influence on Aspergillus biofilm.

PMID- 24910634
TI  - Contribution of Human FcgammaRs to Disease with Evidence from Human Polymorphisms
      and Transgenic Animal Studies.
AB  - The biological activities of human IgG antibodies predominantly rely on a family
      of receptors for the Fc portion of IgG, FcgammaRs: FcgammaRI, FcgammaRIIA,
      FcgammaRIIB, FcgammaRIIC, FcgammaRIIIA, FcgammaRIIIB, FcRL5, FcRn, and TRIM21.
      All FcgammaRs bind IgG at the cell surface, except FcRn and TRIM21 that bind IgG
      once internalized. The affinity of FcgammaRs for IgG is determined by
      polymorphisms of human FcgammaRs and ranges from 2 * 10(4) to 8 * 10(7) M(-1).
      The biological functions of FcgammaRs extend from cellular activation or
      inhibition, IgG-internalization/endocytosis/phagocytosis to IgG transport and
      recycling. This review focuses on human FcgammaRs and intends to present an
      overview of the current understanding of how these receptors may contribute to
      various pathologies. It will define FcgammaRs and their polymorphic variants,
      their affinity for human IgG subclasses, and review the associations found
      between FcgammaR polymorphisms and human pathologies. It will also describe the
      human FcgammaR-transgenic mice that have been used to study the role of these
      receptors in autoimmune, inflammatory, and allergic disease models. 

PMID- 24910636
TI  - Disruption of the ammonium transporter AMT1.1 alters basal defenses generating
      resistance against Pseudomonas syringae and Plectosphaerella cucumerina.
AB  - Disruption of the high-affinity nitrate transporter NRT2.1 activates the priming
      defense against Pseudomonas syringae, resulting in enhanced resistance. In this
      study, it is demonstrated that the high-affinity ammonium transporter AMT1.1 is a
      negative regulator of Arabidopsis defense responses. The T-DNA knockout mutant
      amt1.1 displays enhanced resistance against Plectosphaerella cucumerina and
      reduced susceptibility to P. syringae. The impairment of AMT1.1 induces
      significant metabolic changes in the absence of challenge, suggesting that amt1.1
      retains constitutive defense responses. Interestingly, amt1.1 combats pathogens
      differently depending on the lifestyle of the pathogen. In addition, N starvation
      enhances the susceptibility of wild type plants and the mutant amt1.1 to P.
      syringae whereas it has no effect on P. cucumerina resistance. The metabolic
      changes of amt1.1 against P. syringae are subtler and are restricted to the
      phenylpropanoid pathway, which correlates with its reduced susceptibility. By
      contrast, the amt1.1 mutant responds by activating higher levels of camalexin and
      callose against P. cucumerina. In addition, amt1.1 shows altered levels of
      aliphatic and indolic glucosinolates and other Trp-related compounds following
      infection by the necrotroph. These observations indicate that AMT1.1 may play
      additional roles that affect N uptake and plant immune responses. 

PMID- 24910635
TI  - Dendritic cell-targeted vaccines.
AB  - Despite significant effort, the development of effective vaccines inducing strong
      and durable T-cell responses against intracellular pathogens and cancer cells has
      remained a challenge. The initiation of effector CD8(+) T-cell responses requires
      the presentation of peptides derived from internalized antigen on class I major
      histocompatibility complex molecules by dendritic cells (DCs) in a process called
      cross-presentation. A current strategy to enhance the effectiveness of
      vaccination is to deliver antigens directly to DCs. This is done via selective
      targeting of antigen using monoclonal antibodies directed against endocytic
      receptors on the surface of the DCs. In this review, we will discuss
      considerations relevant to the design of such vaccines: the existence of DC
      subsets with specialized functions, the impact of the antigen intracellular
      trafficking on cross-presentation, and the influence of maturation signals
      received by DCs on the outcome of the immune response. 

PMID- 24910637
TI  - Toward atomic force microscopy and mass spectrometry to visualize and identify
      lipid rafts in plasmodesmata.
AB  - Plant cell-to-cell communication is mediated by nanopores called plasmodesmata
      (PDs) which are complex structures comprising plasma membrane (PM), highly packed
      endoplasmic reticulum and numerous membrane proteins. Although recent advances on
      proteomics have led to insights into mechanisms of transport, there is still an
      inadequate characterization of the lipidic composition of the PM where membrane
      proteins are inserted. It has been postulated that PDs could be formed by lipid
      rafts, however no structural evidence has shown to visualize and analyse their
      lipid components. In this perspective article, we discuss proposed experiments to
      characterize lipid rafts and proteins in the PDs. By using atomic force
      microscopy (AFM) and mass spectrometry (MS) of purified PD vesicles it is
      possible to determine the presence of lipid rafts, specific bound proteins and
      the lipidomic profile of the PD under physiological conditions and after changing
      transport permeability. In addition, MS can determine the stoichiometry of intact
      membrane proteins inserted in lipid rafts. This will give novel insights into the
      role of membrane proteins and lipid rafts on the PD structure. 

PMID- 24910638
TI  - Brachypodium distachyon as a model system for studies of copper transport in
      cereal crops.
AB  - Copper (Cu) is an essential micronutrient that performs a remarkable array of
      functions in plants including photosynthesis, cell wall remodeling, flowering,
      and seed set. Of the world's major cereal crops, wheat, barley, and oat are the
      most sensitive to Cu deficiency. Cu deficient soils include alkaline soils, which
      occupy approximately 30% of the world's arable lands, and organic soils that
      occupy an estimated 19% of arable land in Europe. We used Brachypodium distachyon
      (brachypodium) as a proxy for wheat and other grain cereals to initiate analyses
      of the molecular mechanisms underlying their increased susceptibility to Cu
      deficiency. In this report, we focus on members of the CTR/COPT family of Cu
      transporters because their homologs in A. thaliana are transcriptionally
      upregulated in Cu-limited conditions and are involved either in Cu uptake from
      soils into epidermal cells in the root, or long-distance transport and
      distribution of Cu in photosynthetic tissues. We found that of five COPT proteins
      in brachypodium, BdCOPT3, and BdCOPT4 localize to the plasma membrane and are
      transcriptionally upregulated in roots and leaves by Cu deficiency. We also found
      that BdCOPT3, BdCOPT4, and BdCOPT5 confer low affinity Cu transport, in contrast
      to their counterparts in A. thaliana that confer high affinity Cu transport.
      These data suggest that increased sensitivity to Cu deficiency in some grass
      species may arise from lower efficiency and, possibly, other properties of
      components of Cu uptake and tissue partitioning systems and reinforce the
      importance of using brachypodium as a model for the comprehensive analyses of Cu
      homeostasis in cereal crops. 

PMID- 24910639
TI  - Proteome balancing of the maize seed for higher nutritional value.
AB  - Most flowering plant seeds are composed of the embryo and endosperm, which are
      surrounded by maternal tissue, in particular the seed coat. Whereas the embryo is
      the dormant progeny, the endosperm is a terminal organ for storage of sugars and
      amino acids in proteins and carbohydrates, respectively. Produced in maternal
      leaves during photosynthesis, sugars, and amino acids are transported to
      developing seeds after flowering, and during germination they nourish early
      seedlings growth. Maize endosperm usually contains around 10% protein and 70%
      starch, and their composition ratio is rather stable, because it is strictly
      regulated through a pre-set genetic program that is woven by networks of many
      interacting or counteracting genes and pathways. Endosperm protein, however, is
      of low nutritional value due mainly to the high expression of the alpha-zein gene
      family, which encodes lysine-free proteins. Reduced levels of these proteins in
      the opaque 2 (o2) mutant and alpha-zein RNAi (RNA interference) transgenic seed
      is compensated by an increase of non-zein proteins, leading to the rebalancing of
      the nitrogen sink and producing more or less constant levels of total proteins in
      the seed. The same rebalancing of zeins and non-zeins has been observed for maize
      seeds bred for 30% protein. In contrast to the nitrogen sink, storage of sulfur
      is controlled through the accumulation of specialized sulfur-rich proteins in
      maize endosperm. Silencing the synthesis of alpha-zeins through RNAi fails to
      raise sulfur-rich proteins. Although overexpression of the methionine-rich delta
      zein can increase the methionine level in seeds, it occurs at least in part at
      the expense of the cysteine-rich beta- and gamma-zeins, demonstrating a balance
      between cysteine and methionine in sulfur storage. Therefore, we propose that the
      throttle for the flow of sulfur is placed before the synthesis of sulfur amino
      acids when sulfur is taken up and reduced during photosynthesis. 

PMID- 24910640
TI  - Tumors that mimic asbestos-related mesothelioma: time to consider a genetics
      based tumor registry?
AB  - The diagnosis of mesothelioma is not always straightforward, despite known
      immunohistochemical markers and other diagnostic techniques. One reason for the
      difficulty is that extrapleural tumors resembling mesothelioma may have several
      possible etiologies, especially in cases with no meaningful history of amphibole
      asbestos exposure. When the diagnosis of mesothelioma is based on histologic
      features alone, primary mesotheliomas may resemble various primary or metastatic
      cancers that have directly invaded the serosal membranes. Some of these
      metastatic malignancies, particularly carcinomas and sarcomas of the pleura,
      pericardium and peritoneum, may undergo desmoplastic reaction in the pleura,
      thereby mimicking mesothelioma, rather than the primary tumor. Encasement of the
      lung by direct spread or metastasis, termed pseudomesotheliomatous spread, occurs
      with several other primary cancer types, including certain late-stage tumors from
      genetic cancer syndromes exhibiting chromosomal instability. Although
      immunohistochemical staining patterns differentiate most carcinomas, lymphomas,
      and mestastatic sarcomas from mesotheliomas, specific genetic markers in tumor or
      somatic tissues have been recently identified that may also distinguish these
      tumor types from asbestos-related mesothelioma. A registry for genetic screening
      of mesothelioma cases would help lead to improvements in diagnostic criteria,
      prognostic accuracy and treatment efficacy, as well as improved estimates of
      primary mesothelioma incidence and of background rates of cancers unrelated to
      asbestos that might be otherwise mistaken for mesothelioma. This information
      would also help better define the dose-response relationships for mesothelioma
      and asbestos exposure, as well as other risk factors for mesothelioma and other
      mesenchymal or advanced metastatic tumors that may be indistinguishable by
      histology and staining characteristics. 

PMID- 24910641
TI  - Bioinformatics for precision medicine in oncology: principles and application to
      the SHIVA clinical trial.
AB  - Precision medicine (PM) requires the delivery of individually adapted medical
      care based on the genetic characteristics of each patient and his/her tumor. The
      last decade witnessed the development of high-throughput technologies such as
      microarrays and next-generation sequencing which paved the way to PM in the field
      of oncology. While the cost of these technologies decreases, we are facing an
      exponential increase in the amount of data produced. Our ability to use this
      information in daily practice relies strongly on the availability of an efficient
      bioinformatics system that assists in the translation of knowledge from the bench
      towards molecular targeting and diagnosis. Clinical trials and routine diagnoses
      constitute different approaches, both requiring a strong bioinformatics
      environment capable of (i) warranting the integration and the traceability of
      data, (ii) ensuring the correct processing and analyses of genomic data, and
      (iii) applying well-defined and reproducible procedures for workflow management
      and decision-making. To address the issues, a seamless information system was
      developed at Institut Curie which facilitates the data integration and tracks in
      real-time the processing of individual samples. Moreover, computational pipelines
      were developed to identify reliably genomic alterations and mutations from the
      molecular profiles of each patient. After a rigorous quality control, a
      meaningful report is delivered to the clinicians and biologists for the
      therapeutic decision. The complete bioinformatics environment and the key points
      of its implementation are presented in the context of the SHIVA clinical trial, a
      multicentric randomized phase II trial comparing targeted therapy based on tumor
      molecular profiling versus conventional therapy in patients with refractory
      cancer. The numerous challenges faced in practice during the setting up and the
      conduct of this trial are discussed as an illustration of PM application. 

PMID- 24910643
TI  - The Effect of Leptin and Adiponectin on KiSS-1 and KissR mRNA Expression in Rat
      Islets of Langerhans and CRI-D2 Cell Line.
AB  - BACKGROUND: Leptin and adiponectin are the two key metabolic hormones secreted
      from adipocytes to control food intake and energy expenditure. The action of both
      hormones in regulation of Gonadotropin Releasing Hormone (GnRH) secretion from
      the hypothalamus is mediated through Kisspeptins. Kisspeptins are products of
      KiSS-1 gene. Leptin and adiponectin are modulators of KiSS-1 expression in the
      hypothalamus. These peptides have also important roles in pancreatic beta-cells
      to control insulin synthesis and secretion and their receptors are detected in
      Langerhans islets. We hypothesized that leptin and adiponectin might alter KiSS-1
      and Kiss Receptor mRNA expression in the islets. OBJECTIVES: The aim of this
      study is to investigate any modulatory effect that leptin and adiponectin may
      have on the expression of Kiss-1 and KiSSR gene in Langerhans islets. MATERIALS
      AND METHODS: We isolated the islets from adult male rats by collagenase and
      cultured CRI-D2 cell lines to investigate the effect of leptin and adiponectin.
      Then, we incubated them with different concentrations of leptin and adiponectin
      for 24 hours. After that, RNA was extracted from the islets and CRI-D2 cells and
      transcripted to cDNA. KiSS-1 and KissR expression levels were evaluated by real
      time PCR. RESULTS: In islet and CRI-D2 cells, leptin increased the KiSS-1 mRNA
      expression significantly, but adiponectin decreased it was expected. CONCLUSIONS:
      These findings indicated the possibility that KiSS-1 mRNA expression is a
      mediator of leptin and adiponectin function in the islets.

PMID- 24910642
TI  - Transposable elements in cancer as a by-product of stress-induced evolvability.
AB  - Transposable elements (TEs) are ubiquitous in eukaryotic genomes. Barbara
      McClintock's famous notion of TEs acting as controlling elements modifying the
      genetic response of an organism upon exposure to stressful environments has since
      been solidly supported in a series of model organisms. This requires the TE
      activity response to possess an element of specificity and be targeted toward
      certain parts of the genome. We propose that a similar TE response is present in
      human cells, and that this stress response may drive the onset of human cancers.
      As such, TE-driven cancers may be viewed as an evolutionary by-product of
      organisms' abilities to genetically adapt to environmental stress. 

PMID- 24910646
TI  - Evaluation of anteroposterior lip positions in the most-favored Iranian facial
      profiles using silhouette.
AB  - OBJECTIVE: One of the most important goals of orthodontic treatment is to create
      an esthetic, well balanced facial profile. However, the components of a well
      balanced Iranian facial profile have not yet been established. The purpose of
      this study was to evaluate the anteroposterior lip position of the Iranian
      population and to compare the perception of orthodontists, dental students and
      orthodontic patients using a series of silhouettes with varying anteroposterior
      lip positions. MATERIALS AND METHODS: Average female and male silhouette profiles
      were constructed from the profiles of 30 Iranian men and women with a normal
      skeletal relationship. The lips in each average profile were protruded or
      retruded in 2-mm increments and the 7 images were arranged randomly. Thirty
      orthodontists, 30 dental students and 30 orthodontic patients were asked to score
      each silhouette from 1 (very bad) to 5 (very good). RESULTS: Both the
      orthodontists and the students preferred the average profile for men and slightly
      more retruded lip position for women. Orthodontic patients had a wide range of
      preference for men and selected more retruded lip positions for women. The least
      favored profile was the most protrusive in the 3 groups. CONCLUSION: These
      findings suggest that Iranian orthodontists, dental students and orthodontic
      patients prefer an average profile for men and slightly retruded profiles for
      women.

PMID- 24910647
TI  - The effect of thermocycling on tensile bond strength of two soft liners.
AB  - OBJECTIVE: Failure of soft liners depends mostly on separation from the denture
      base resin; therefore measurement of the bond strength is very important. The
      purpose of this study was to compare the tensile bond strength of two soft liners
      (Acropars, Molloplast-B) to denture base resin before and after thermocycling.
      MATERIALS AND METHODS: Twenty specimens fromeach of the two different soft liners
      were processed according to the manufacturer's instructions between two
      polymethyl methacrylate (PMMA) sheets. Ten specimens in each group were
      maintained in 37 degrees C water for 24 hours and 10 were thermocycled (5000
      cycles) among baths of 5 degrees  and 55 degrees C. The tensile bond strength was
      measured using a universal testing machine at a crosshead speed of 5 mm/min. Mode
      of failure was determined with SEM (magnification *30). Two-way ANOVA was used to
      analyze the data. RESULTS: The mean and standard deviation of tensile bond
      strength of Acropars and Molloplast-B before thermocycling were 6.59+/-1.85
      and1.51+/-0.22 MPa, respectively and 5.89+/-1.52 and1.37+/-0.18 MPa, respectively
      after thermocycling. There was no significant difference before and after
      thermocycling. Mode of failure in Acropars and Molloplast-B were adhesive and
      cohesive, respectivley. CONCLUSION: The bond strength of Acropars was
      significantly higher than Molloplast-B (P<0.05).

PMID- 24910644
TI  - The time of prenatal androgen exposure affects development of polycystic ovary
      syndrome-like phenotype in adulthood in female rats.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common
      reproductive disorders in women. Previous studies have shown that prenatal
      exposure of female fetuses to androgen can be considered an important factor in
      the development of PCOS. OBJECTIVES: In the present study we aimed to examine the
      effects of prenatal exposure of female rat fetuses to previously documented doses
      of testosterone on different embryonic days on the development of PCOS phenotype
      in adulthood. MATERIALS AND METHODS: Pregnant rats were divided into four groups,
      experimental and control groups. Three mg of free testosterone was administered
      subcutaneously to experimental group 1 on gestational days 16-19, daily and 20 mg
      on day 20, to experimental group 2, and the controls received solvent at the same
      times. Female offspring of these mothers aged between 90-100 days were examined
      for development and function of the reproductive system. Independent-sample
      student t test was used to compare the results between the experimental groups
      and controls. RESULTS: Anogenital distance (P < 0.001) and clitoris length were
      significantly increased in the offspring of both experimental groups (P < 0.001
      and P < 0.05 respectively). Nipples were not formed in the offspring of
      experimental group 1, whereas in experimental group 2 the number of nipples was
      unchanged. Vaginal length was significantly decreased in the offspring of
      experimental group 1 (P < 0.001), whereas in experimental group 2, no significant
      difference was observed. In the offspring of experimental group 1, hormonal
      profiles did not differ, but in experimental group 2, levels of testosterone (P <
      0.05) and LH (P < 0.01) were significantly increased, but estrogen (P < 0.05) and
      anti-Mullerian hormone levels (P < 0.001) were significantly decreased. A
      significant increase in the number of preantral and antral follicles was observed
      in the ovaries of offspring of experimental group 1 (P < 0.05); whereas there was
      no such a difference in experimental group 2. CONCLUSIONS: The time of prenatal
      exposure to androgens may have a significant role in the development of PCOS.
      Increased prenatal androgen levels are associated with hormonal changes and
      morphological disorders of the reproductive system. Therefore, avoiding exposure
      to androgen excess during critical periods of fetal development may prevent or
      reduce adulthood PCOS manifestations caused by prenatal excess androgen.

PMID- 24910648
TI  - Effect of a common diet and regular beverage on enamel erosion in various
      temperatures: an in-vitro study.
AB  - OBJECTIVE: This study compared diet and regular Coca-Cola on enamel erosion in
      cold and room temperatures. MATERIALS AND METHODS: Seventy five enamel specimens
      were prepared and divided into 5 equal groups (N=15) as follows: Group 1: regular
      beverage at room temperature, Group 2: regular beverage at refri-gerator
      temperature, Group 3: diet beverage at room and Group 4: diet beverage at refrige
      rator temperature. The specimens were immersed in the regular or diet beverage
      (Coca-Cola, trade mark regd. Khoshgovar Co., Tehran, Iran) at room (20 degrees C)
      or refrigerator (2 degrees C) temperatures for 20 minutes, 3 times per day for 7
      days. Specimens in the control subjects (group 5) were placed in synthetic saliva
      at room temperature for 7 days. The hardness of specimens was tested using
      Vickers test under 500 gr loads for 5 seconds. The data were analyzed using two
      way ANOVA and Tukey tests. RESULTS: The mean and standard deviations of micro
      hardness values of the studied groups were as follow: G1: 304.26+/-29.71, G2:
      285.53+/-42.14, G3: 279.06+/-39.52, G4: 266.80+/-23.98 and G5: 319+/- 30.79.
      There was a significant difference in the beverage type as the main factor
      (p<0.05), but temperature factor and their interaction effect on enamel hardness
      showed no significant difference (p>0.05). Tukey tests showed that there were
      significant differences between control and diet groups as well as regular and
      diet groups. CONCLUSION: Diet Coca-Cola is more erosive than the regular type and
      the temperature of the beverages used had no significant influence on enamel
      erosion.

PMID- 24910649
TI  - Fracture resistance of teeth restored with direct and indirect composite
      restorations.
AB  - OBJECTIVE: Tooth fracture is a common dental problem. By extension of cavity
      dimensions, the remaining tooth structure weakens and occlusal forces may cause
      tooth fracture. The aim of this study was to evaluate and compare the fracture
      resistance of teeth restored with direct and indirect composite restorations.
      MATERIALS AND METHODS: Sixty-five sound maxillary premolar teeth were chosen and
      randomly divided into five groups each comprising thirteen. Fifty-two teeth
      received mesio-occluso-distal (MOD) cavities with 4.5mm bucco-lingual width, 4mm
      pulpal depth and 3mm gingival depth and were divided into the following four
      groups. G-1: restored with direct composite (Z-250, 3M/ESPE) with cusp coverage,
      G-2: restored with direct composite (Z-250) without cusp coverage, G-3: restored
      with direct composite (Gradia, GC-international) with cusp coverage, G-4:
      restored with indirect composite (Gradia, GC-International) with cusp coverage.
      Intact teeth were used in G-5 as control. The teeth were subjected to a
      compressive axial loading using a 4 mm diameter rod in a universal testing
      machine with 1 mm/min speed. Data were analyzed using one-way ANOVA and Tukey
      tests. RESULTS: THE MEAN FRACTURE STRENGTH RECORDED WAS: G-1: 1148.46N+/-262, G
      2: 791.54N+/-235, G-3: 880.00N+/-123, G-4: 800.00N+/-187, G-5: 1051.54N+/-345.
      ANOVA revealed significant differences between groups (p<0.05). Tukey test showed
      significant difference between group 1 and the other groups. There was no
      significant difference among other groups. CONCLUSION: Direct composite (Z-250)
      with cusp coverage is a desirable treatment for weakened teeth. Treatment with Z
      250 without cusp coverage, direct and indirect Gradia with cusp coverage restored
      the strength of the teeth to the level of intact teeth.

PMID- 24910651
TI  - Radiographic localization of the mental foramen and mandibular canal.
AB  - OBJECTIVE: Accurately localizing the mental foramen and mandibular canal is
      important when administering local anesthesia and performing surgery; therefore,
      knowing the normal range of the possible locations is essential. Our purpose was
      to assess the location of the mental foramen and mandibular canal in an Iranian
      population using panoramic radiography. MATERIALS AND METHODS: Standard panoramic
      radiographies were performed. The positions of 100 mental foramens were
      evaluated. The distances from the center of the mental foramen to the superior
      and inferior borders of the mandible and to the apexes of the first and second
      premolar were measured. The distance of the mental foramens from the mandibular
      midline and the diameter of the mandibular canal in the mental foramen connection
      were also measured. RESULTS: Among 100 mental foramens, 6% were positioned under
      the first premolar, 24% were between the first and second premolars, 67% were
      under the second premolar, and the remaining 3% were behind the second premolar.
      The mean distance from the mental foramen to the mandibular midline was 27.77+/
      3.20 mm. The mean diameter of the mandibular canal in the mental foramen
      connection was 3.09+/-0.69mm. CONCLUSION: The mental foramen was near the second
      premolar and the inferior border of the mandible. This information can be used to
      perform safer mental nerve blocks in surgical interventions.

PMID- 24910650
TI  - Effect of endodontic irrigants on microtensile bond strength to dentin after
      thermocycling and long-term water storage.
AB  - OBJECTIVE: The bond strength of adhesives in irrigated dentin behaves differently
      over time. The aim of this study was to evaluate the influence of long-term water
      storage and thermocycling on the microtensile bond strength of adhesive systems
      to dentin irrigated with endodontic solutions. MATERIALS AND METHODS: Sixty human
      molars were used after removal of the occlusal portion and exposure of the dentin
      by grinding. The specimens were irrigated with 2.5% NaOCl for 30 minutes and then
      17% EDTA for 5 minutes and assigned to six groups according to the adhesive
      system (n=10): G1 and G2-Clearfil SE Bond; G3 and G4-Single Bond 2; and G5 and G6
      XP Bond. The teeth were restored with composite and were subjected to water
      storage for different time periods. G1, G3 and G5 were stored for 24 h; G2, G4
      and G6 were stored for 6 months and were subjected to thermocycling (12,000
      cycles, 5 degrees C to 55 degrees C, 500 cycles per week for 6 months). After
      storage, the tooth/restoration assembly was sectioned to obtain four sticks of
      approximately 1 mm(2), for microtensile bond strength testing. The results were
      analyzed by two-way ANOVA and Tukey's test. RESULTS: Significant differences were
      observed among the adhesives (p<0.01). No significant differences were observed
      in the microtensile bond strength between samples after 24 hours of storage
      without thermocycling and after 6-month storage with 12,000 cycles (p<0.05).
      CONCLUSION: The bond strengths of G5 and G6 after irrigation with 2.5% NaOCl and
      17% EDTA were significantly different from those of other groups. Long-term water
      storage/thermocycling had no effect on bond strength to dentin.

PMID- 24910652
TI  - Evaluation of the association between periodontal parameters, osteoporosis and
      osteopenia in post menopausal women.
AB  - OBJECTIVE: Different studies have reported contradictory results about the effect
      of osteoporosis on periodontal status. We performed this study to evaluate the
      periodontal status of menopausal women by methods with enough accuracy and
      confidence. MATERIALS AND METHODS: This study was performed based on the
      evaluation of bone mineral density using dual energy X-ray absorptiometry in
      2010. A total of 60 patients who met the inclusion criteria were selected and
      divided into three groups of osteoporosis, osteopenia, and normal. Then,
      evaluation of periodontal markers such as pocket depth (DP), attachment loss
      (AL), and tooth loss (TL) was performed by a dental student. A panoramic
      radiography was performed for those who were suspicious of periodontal disease
      and bone decline. Finally, evaluation of the periodontal indexes was compared
      among the three groups using ANOVA with 95% confidence interval. RESULTS: Mean
      bone decline was higher in the osteoporosis group compared to the other two
      groups, but the difference was not significant (P=0.065). In addition, mean of
      plaque index (P=0.123), pocket depth (P=0.856), attachment loss (p=0.525), and
      tooth loss (p=0.884), the number of people with attachment loss >= 2millimeter
      (P=0.866) and the number of people with alveolar bone loss >= 2 millimeter
      (P=0.348) were not significantly different between the three groups. CONCLUSION:
      In this study, no significant difference was observed between the three groups in
      terms of plaque index, pocket depth, attachment loss, or tooth loss. However,
      further studies are required that could control all the possible confounding
      variables.

PMID- 24910653
TI  - The effect of implant length and diameter on the primary stability in different
      bone types.
AB  - OBJECTIVE: The focus of this paper is to evaluate the influence of mechanical
      characteristics of the implant on primary stability in different bone types,
      based on resonance frequency analysis (RFA). MATERIALS AND METHODS: A number of
      60 Nobel Biocare Replace Select TiUnit Tapered implants of two different lengths
      (10 mm and 13 mm) and three different widths as 3.4 mm (narrow platform (NP)),
      4.3 mm (regular platform (RP)) and 5 mm (wide platform (WP)) were placed into two
      different groups of bone blocks. Bone blocks were different in bone quality, but
      similar to bone types D1 and D3. Immediately, after implant placement, implant
      stability quotient (ISQ) was measured using the Osstell mentor device. RESULTS:
      ISQ values for implant placements in D1 bone were significantly higher than those
      for implants placed in D3 bone. In D1 bone, the implant length did not make any
      significant difference in primary stability; however, in D3 bone, the primary
      stability of the implant increased when longer implants were utilized. NP
      implants presented significantly lower ISQ values compared to the two wider
      implants. CONCLUSION: In cases of low bone quality, the optimum increase in the
      implant length and diameter should be taken into account to achieve higher
      primary stability.

PMID- 24910654
TI  - Can dental pulp calcification predict the risk of ischemic cardiovascular
      disease?
AB  - OBJECTIVE: To report the association of pulp calcification with that of
      cardiovascular disease (CVD) using digital panoramic dental radiographs.
      MATERIALS AND METHODS: Digital panoramic radiographs of patients referred from
      the angiography department were included if the patient was under 55 years old
      and had non-restored or minimally restored molars and canines. An oral and
      maxillofacial radiologist evaluated the images for pulpal calcifications in the
      selected teeth. The sensitivity, specificity, positive predictive value and
      negative predictive value of panoramic radiography in predicting CVD were
      calculated. RESULTS: Out of 122 patients who met the criteria, 68.2% of the
      patients with CVD had pulp chamber calcifications. Pulp calcification in
      panoramic radiography had a sensitivity of 68.9% to predict CVD. CONCLUSION: This
      study demonstrates that patients with CVD show an increased incidence of pulp
      calcification compared with healthy patients. The findings suggest that pulp
      calcification on panoramic radiography may have possibilities for use in CVD
      screening.

PMID- 24910655
TI  - Evaluation of shear bond strength of orthodontic brackets bonded with nano-filled
      composites.
AB  - OBJECTIVES: The purpose of this study was to evaluate the shear bond strength
      (SBS) of orthodontic brackets bonded with two types of nano-composites in
      comparison to a conventional orthodontic composite. MATERIALS AND METHODS: Sixty
      extracted human first premolars were randomly divided into 3 groups each
      containing 20 teeth. In group I, a conventional orthodontic composite (Transbond
      XT) was used to bond the brackets, while two nano-composites (Filtek TM Supreme
      XT and AELITE Aesthetic Enamel) were used in groups II and III respectively. The
      teeth were stored in distilled water at 37 degrees C for 24 hours, thermocycled
      in distilled water and debonded with a universal testing machine at a crosshead
      speed of 1 mm/min. The adhesive remnant index (ARI) was also evaluated using a
      stereomicroscope. RESULTS: AELITE Aesthetic Enamel nano-composite revealed a SBS
      value of 8.44+/-2.09 MPa, which was higher than Transbond XT (6.91+/-2.13) and
      Filtek TM Supreme XT (6.04+/-2.01). Statistical analysis revealed a significant
      difference between groups II and III (P < 0.05). No significant difference was
      found between groups I and III, and between groups I and II (P > 0.05).
      Evaluation of ARI showed that Transbond XT left fewer adhesive remains on teeth
      after debonding. CONCLUSION: Results of this study indicate that the
      aforementioned nano-composites can be successfully used for bonding orthodontic
      brackets.

PMID- 24910656
TI  - Evaluation of bite force after open reduction and internal fixation using
      microplates.
AB  - The primary aim of this study is to determine maximum bite force in molar and
      incisor regions of healthy individuals, to evaluate the bite force after open
      reduction and internal fixation of mandibular fractures using micro plates, for a
      period of up to 6 weeks and to determine the rate of recovery of maximum bite
      force in an Indian population. 

PMID- 24910657
TI  - Correction of maxillofacial deformities in a patient with unilateral coronal
      craniosynostosis (plagiocephaly): a case report and a review of literatures.
AB  - Plagiocephaly (oblique skull) is premature fusion of one of the coronal sutures.
      Frontal plagiocephaly is a rare congenital deformity in the skull that is the
      most complicated form of craniosynostosis to treat. Examination of all sutures is
      necessary for diagnosis of craniosynostosis In this article, a 10-month-old,
      healthy girl with deformity of the right forehead and orbit that is caused by
      frontal plagiocephaly and coronal unilateral synostosis is presented. This
      abnormality was corrected by frontal craniotomy and fronto-orbital complex
      advancement under general anesthesia. An exact clinical and radiographic
      (Multislice CT scan with 3-dimensional three dimensional reconstruction)
      examination with the suitable time of surgery is necessary for diagnosis of skull
      abnormality and prevention of treatment delay. Furthermore, 3D stereo-photo
      grammetry is a radiation-free, non invasive method for evaluating the growth
      pattern of children in long term. 

PMID- 24910658
TI  - Comparison of oral lesion prevalence between renal transplant patients and
      dialysis patients.
AB  - OBJECTIVE: Renal transplantation is performed in patients with end stage renal
      disease as the best treatment plan. However, different complications may occur in
      these patients due to the direct consequences of the renal disease or drug
      induced suppression of the body immune system. The main objective of the present
      study was to compare different oral lesions in patients receiving renal
      transplantation with the patients undergoing dialysis referred to two hospitals
      in Tehran, Iran. MATERIALS AND METHODS: In this cross-sectional study, 93 renal
      transplant patients who had received renal transplant at least 6 months prior to
      our study, were selected from their records at the hospitals. Furthermore, 93
      candidates of renal transplantation were selected as the control group. The
      patients in both case and control groups underwent oral examinations and the
      results were analyzed by chi-square test and Spearman correlation coefficient.
      RESULTS: At least one oral lesion was found in 30 (32.2%) patients in the renal
      transplant group and 8 (8.6%) patents in the control subjects. The difference
      between the two groups was statistically significant (p<0.0001). The most
      prevalent lesion was xerostomia observed in 20 patients of the renal transplant
      group and 4 patients in the control group. The odds ratio of cyclosporine and
      amlodipine and the effect of these in increasing the risk of oral lesions was
      1.21 and 1.02, respectively in renal transplant recipients. CONCLUSION: The
      results of the study showed that renal transplantation significantly increases
      the risk of related oral lesions. Therefore, renal transplant recipients must
      undergo regular oral examinations in order to find any suspicious lesion(s) as
      soon as possible to treat them.

PMID- 24910659
TI  - DNA damage in oral mucosa cells of patients with fixed orthodontic appliances.
AB  - OBJECTIVE: The release of toxic metal ions from orthodontic alloys has induced
      concerns regarding the biocompatibility of fixed appliances. This study
      investigated the genotoxic effect of metal appliances in a sample of patients
      undergoing fixed orthodontic treatment. MATERIALS AND METHODS: The study included
      twenty-five healthy individuals requiring orthodontic therapy in both jaws. The
      patients were treated by stainless steel orthodontic brackets and nickel-titanium
      or stainless steel arch wires. The oral mucosa cells were gathered just before
      the appliance placement and 9 months later. The cells were centrifuged, fixed and
      dropped onto slides. After staining, the micronucleus (MN) assay was used to
      determine genome alteration. The data were analyzed by paired sample t-test.
      RESULTS: The mean micronuclei frequency in the buccal mucosa was 10.6 +/- 5.7 per
      1000 cells before the appliance placement and 9.2 +/- 6.37 per 1000 cells 9
      months later. No significant difference was found in the MN count before and 9
      months after therapy (p=0.336). CONCLUSION: Under the conditions used in this
      study, application of fixed orthodontic appliances did not expose healthy
      individuals to increased risk of DNA damage in oral mucosa cells.

PMID- 24910660
TI  - Evaluation of Two New Electronic Apex-Locator-Controlled Handpieces Using a NiTi
      Rotary File: An In Vitro Study.
AB  - OBJECTIVES: The aim of this in-vitro study was to compare the accuracy of two new
      electronic apex-locator controlled handpieces (EALHs) using the first rotary Mtwo
      file while rotating in the canal. MATERIALS AND METHODS: A total of 36 extracted
      mandibular molar teeth were selected. The lengths of the mesio-buccal canals to
      the major foramina were measured directly using a size 10 K-file introduced in
      the canal until the tip was visible under a loupe and then 0.5 mm was subtracted
      from the recorded lengths as the actual working lengths (AWLs). Subsequently, the
      teeth were randomly assigned to two groups and embedded in an alginate model.
      Auto-stop function of the EALHs was preset at "0.5" mark and then electrical
      working lengths (EWLs) in groups 1 and 2 were recorded by VDW GOLD and Dentaport
      ZX, respectively. Analysis of variance (ANOVA, 1-way) and Tukey pairwise multiple
      comparison intervals (0.05) were used to compare the accuracy of the two
      electronic devices. RESULTS: For VDW GOLD, 61.1% of the measurements were within
      +/-0.5 mm and 88.9% were within +/-1 mm of the AWL. For Dentaport ZX, 88.9% of
      the measurements were within +/-0.5 mm and 94.4% were within +/-1mm of the AWL.
      There was no significant difference between AWLs and EWLs (p=0.466 for Dentaport
      ZX and p=0.283 for VDW Gold) and between the accuracy of the two devices in
      determining the EWL (p=0.8). CONCLUSION: Both Dentaport ZX and VDW Gold were
      suitable for determining working length using a rotary file. To avoid over
      instrumenting the canal, we recommend setting the devices to automatically stop
      or reverse the rotary file at 1 mm level.

PMID- 24910661
TI  - Comparative evaluation of physical properties of four tissue conditioners relined
      to modeling plastic material.
AB  - OBJECTIVE: Little is known about the interaction of tissue conditioners and
      modeling plastics. This study evaluates the influence of a variety of commercial
      tissue conditioners on alteration of viscoelastic properties of modeling
      plastics. MATERIALS AND METHODS: In this in vitro study, the dynamic viscoelastic
      properties of four commercially available tissue conditioners (TC), Visco-gel
      (VG), GC Soft-Liner (SL), FITT (FT), and Coe Comfort (CC), relined to modeling
      plastics with a thickness of 2mm were evaluated after 1 and 7 days of water
      immersion with the use of storage modulus, loss modulus, and tan delta
      parameters. Values for these three parameters for each tissue conditioner were
      statistically analyzed by Kruskal Wallis and Mann Whitney tests with P value sets
      at<0.05. RESULTS: Complex modulus and loss tangent values of TC were not
      significantly different among specimens containing 0, 2, 5 and 10 wt.%-SZ,
      respectively. In FT and TC containing 2 wt.%-SZ, these values were not
      significantly different between 1 and 28 days in both water- and saliva
      immersions. CONCLUSION: The results suggest that relining with modeling plastics
      does affect TC's inherent dynamic viscoelastic properties, while the other tissue
      conditioners investigated may be found to have changed viscoelastic properties as
      a consequence of vicinity to the modeling plastics.

PMID- 24910662
TI  - Evaluation of the root canal morphology of mandibular second premolars in an
      Iranian population.
AB  - OBJECTIVE: A detailed knowledge of root canal anatomy is a prerequisite for
      successful endodontic treatment. Such information is highly dependent upon the
      ethnicity of the population of interest. Lack of sufficient national information
      concerning internal anatomy can lead clinicians to increase their rate of
      treatment success. The aim of this study was to evaluate external root morphology
      and root canal anatomy of mandibular second premolars in an Iranian population.
      MATERIALS AND METHODS: Two hundred seventeen human extracted mandibular second
      premolars were selected. Each tooth was radiographed both mesiodistally and
      buccolingually. Then, access cavities were prepared for each tooth and root canal
      negotiated before being immersed into 1% fuchsine solution. Teeth were de
      coronated and their roots sectioned into three equal (cervical, middle and
      apical) parts. Cross sections were visualized under 40X magnification. RESULTS:
      Among all roots examined, 132 were straight both mesiodistally and
      buccolingually, 56 were mesiodistally curved, but buccolingually straight, 11
      were mesiodistally straight, but buccolingually curved and 18 samples were curved
      in both aspects. Internal anatomical evaluation showed 198 samples (91.24%) with
      a single and 19 (8.75%) with more than one canal. CONCLUSION: Although straight
      roots are common in mandibular second premolars, curvatures in mesiodistal,
      buccolingual or both directions are not uncommon in the Iranian population.
      Single-canalled roots are also frequent in these teeth, but Vertucci's types II,
      III, IV, V, and C-shaped configurations are also encountered.

PMID- 24910663
TI  - Correlation between dental arch width and sagittal dento-skeletal morphology in
      untreated adults.
AB  - OBJECTIVE: Dental arch form is one of the most important characteristics of
      dentition. However, this dimension usually receives less attention in diagnosis
      or treatment planning and orthodontic patients are traditionally classified with
      regard to their sagittal characteristics. The objectives of this study were to
      investigate if a relationship exists between the dental arch width (transverse
      dimension) and sagittal skeletal and dental parameters in orthodontic patients.
      MATERIALS AND METHODS: Dental casts and lateral cephalograms of 108 consecutive
      untreated Iranian patients (47 males and 61 females) between 16 and 31 years of
      age were evaluated. Arch width (AW) parameters including upper and lower inter
      molar width (UIMW and LIMW) and upper and lower inter-canine width (UICW and
      LICW) were measured by a digital caliper. Sagittal parameters included SNA and
      SNB angle and Wits' appraisal obtained from lateral cephalograms in addition to
      upper and lower arch length (UAL and LAL) obtained from dental casts. The
      correlation between the aforementioned parameters was evaluated applying Pearson
      correlation coefficients. Molar and canine relationship according to Angle's
      classification was also recorded and the means of all parameters were compared
      between three occlusal relationship classes and two gender groups by means of two
      way ANOVA. RESULTS: According to statistical analysis a significant positive
      correlation between sagittal parameters and arch width measures exists between
      SNA and UICW and between LICW and LAL. Upper and lower ICW were significantly
      correlated, the relationship between upper and lower IMW and between UAL and LAL
      were significant. Among sagittal measures, both UAL and LAL were correlated with
      the ANB angle. The means of arch width parameters in three occlusal classes were
      not significantly different. CONCLUSION: The only significant correlation between
      arch width and sagittal parameters existed between UICW and SNA angle and between
      LICW and LAL. No significant difference of the arch width parameter was observed
      between the three occlusal classes.

PMID- 24910664
TI  - Effect of atorvastatin on orthodontic tooth movement in male wistar rats.
AB  - OBJECTIVES: Statins are used as cholesterol-lowering drugs by many patients and
      have been recently shown to affect bone metabolism. The aim of this study was to
      determine the effect of atorvastatinon on orthodontic tooth movement (OTM) in
      rats. MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats were
      randomly divided into three groups of 12 samples each. Group A, served as control
      with no medication while groups B and C received a daily gavage of carboxymethyl
      cellulose (CMC) as vehicle and atorvastatin (5 mg/kg) as test substance,
      respectively. In all three groups, 6mm nickel-titanium closed-coil springs were
      ligated between the maxillary incisors and first left molars to deliver an
      initial force of 60g. Tooth movement was measured following sacrifice, 21 days
      after appliance insertion. Root resorption, PDL width and osteoclast number were
      histologically evaluated and compared between the groups. RESULTS: The mean
      amount of tooth movement was 0.62 mm in group A, 0.59 mm in group B and 0.38 mm
      in group C. OTM reduction following administration of atorvastatin was
      statistically significant (p<0.05), but there was no significant difference in
      the studied histologic variables among the three groups (p>0.05). CONCLUSION:
      According to the results obtained in the current study, atorvastatin appears to
      reduce tooth movement in rats; however its effect on osteoclasts, especially
      osteoclastic function, requires further investigation.

PMID- 24910665
TI  - Push-out bond strength of bioceramic materials in a synthetic tissue fluid.
AB  - OBJECTIVE: This study compared the push-out bond strength of EndoSequence Root
      Repair Material (ERRM) and Bioaggregate (BA), new bioceramic materials, to that
      of mineral trioxide aggregate (MTA) after incubation in phosphate-buffered saline
      (PBS), a synthetic tissue fluid, for either 1 week or 2 months. MATERIALS AND
      METHODS: One-hundred and twenty root sections were filled with ProRoot MTA, BA,
      or ERRM. Each tested material was then randomly divided into two subgroups (n =
      20): root sections were immersed in PBS for 1 week or 2 months. The bond
      strengths were measured using a universal testing machine. After that, the
      failure modes were examined with stereomicroscopy and scanning electron
      microscopy (SEM). The push-out data and failure mode categories were analyzed by
      two-way ANOVA and chi-square tests, respectively. RESULTS: The bond strength of
      ERRM was significantly higher than that of BA and MTA at both incubation periods.
      No significant difference was found between the bond strength of MTA and BA at
      either 1 week or 2 months. Increasing the incubation time to 2 months resulted in
      a significant increase in bond strength of all the materials. The failure mode
      was mainly mixed for MTA and BA, but cohesive for ERRM at both incubation
      periods. CONCLUSION: ERRM had significantly higher bond strength to root canal
      walls compared to MTA and BA. Increasing the incubation time significantly
      improved the bond strength and bioactive reaction products of all materials.

PMID- 24910667
TI  - Sequential supernumerary teeth development in a non-syndromic patient; report of
      a rare case.
AB  - Isolated impacted supernumerary teeth are quite rare, but they can be seen
      associated with several syndromes such as cleidocranial dysostosis or Gardner's
      syndrome. This article aims to discuss a case of sequential formation of
      supernumerary teeth with no other associated disease or syndrome. A 17-year-old
      Iranian male with 8 impacted supernumerary teeth was referred to the department
      of pediatric dental clinic at Shahid Beheshti Medical University in Tehran with a
      history of several impacted unerupted teeth. Repeated and periodical clinical and
      radiographic examinations revealed newly formed teeth buds in unusual dental
      ages. All extra teeth were associated with generalized enamel hypoplasia to some
      degree on their relative permanent adjacent teeth. The patient did not have any
      record of a systemic disease or any syndromic condition to relate his dental
      problem to. This rare condition involved repeated and continued formation of
      extra teeth out of the normal numbers and dental age evident in serial
      radiographs. 

PMID- 24910666
TI  - The effect of storage temperature on mechanical properties of gutta-percha and
      resilon.
AB  - OBJECTIVES: To compare the mechanical properties of Resilon and gutta-percha
      cones after storing at three different temperatures. MATERIALS AND METHODS: One
      hundred standardized size 40/02 gutta-percha cones and 100 Resilon cones were
      randomly divided into four groups. The first group of the materials were tested
      immediately after receipt as the control group. The other three were stored in
      their packages at -12 degrees C, 4+/- 1 degrees C and 22+/- 2 degrees C for three
      months. Then, obturating cones were loaded by a tensile force at the rate of
      5mm/min. Physical integrity of gutta-percha and Resilon cones were also evaluated
      according to ISO6877. The data were analyzed by one-way analysis of variance,
      post hoc and t-test. A p-value <0.05 was considered significant. RESULTS: The
      elasticity modulus of gutta-percha reduced significantly after three months
      storage at -12 degrees C, while storage at 4+/-1 degrees C and 22+/- 2 degrees C
      had no effect on its modulus of elasticity. In addition, the tensile strength of
      gutta-percha did not change after three months of storing. The modulus of
      elasticity of Resilon reduced significantly in all storage conditions; however,
      its tensile strength did not change. The storage conditions did not have a
      significant effect on the elongation rate of gutta-percha and Resilon. Eighty
      percent of gutta-percha cones lost their physical integrity after storage in 4 
      degrees +/-1C and 22+/-2 degrees C. However, storage conditions had no impact on
      the physical integrity of Resilon cones. CONCLUSION: Storing gutta-percha at -12
      degrees C can benefit its properties, while keeping Resilon at both refrigerated
      and room conditions can preserve its mechanical properties.

PMID- 24910668
TI  - Intraoral mass presenting as maxillary sinus carcinoma: a case report.
AB  - Sinonasal undifferentiated carcinoma is an extremely rare malignancy of the
      paranasal sinuses and nasal cavity. It is of unknown etiology, and occurs more
      commonly in the elderly men, with a routinely shown aggressive behavior and poor
      prognosis for survival. Radiographically, it looks like severe osteomyelitis.
      Histopathologic study is essential to confirm diagnosis, and the undifferentiated
      histologic appearance often necessitates immunohistochemical studies for
      differentiation from other high-grade neoplasms. We present an 83-year-old man
      complaining of pain and unilateral swelling on the left side of the face due to a
      rare malignant tumor of maxillary sinus origin, a sinonasal undifferentiated
      carcinoma. He underwent hemimaxillectomy and radiotherapy, but refused
      chemotherapy. Maxillary sinus malignancy may be presented with unspecific
      symptoms mimicking sinusitis or dental pain. Coming across such symptoms, the
      physician or dentist must consider malignancies as well, and carry out medical
      and dental workups. 

PMID- 24910669
TI  - Root canal treatment of a mandibular second premolar with three roots and canals 
      an anatomic variation.
AB  - Dental anatomical variations play a significant role in the diagnosis and a
      successful treatment outcome in endodontics. It is essential for the clinician to
      have a clear picture and understanding of the pulpal anatomy and its variations.
      In a mandibular second premolar, it is rare to find extra roots and canals. The
      aim of the present article is to report a case about the successful diagnosis,
      and clinical management of a three-rooted mandibular second premolar with three
      independent roots and canals. 

PMID- 24910670
TI  - Effectiveness of four different final irrigation activation techniques on smear
      layer removal in curved root canals : a scanning electron microscopy study.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of apical negative
      pressure (ANP), manual dynamic agitation (MDA), passive ultrasonic irrigation
      (PUI) and needle irrigation (NI) as final irrigation activation techniques for
      smear layer removal in curved root canals. MATERIALS AND METHODS: Mesiobuccal
      root canals of 80 freshly extracted maxillary first molars with curvatures
      ranging between 25 degrees  and 35 degrees  were used. A glide path with #08-15 K
      files was established before cleaning and shaping with Mtwo rotary instruments
      (VDW, Munich, Germany) up to size 35/0.04 taper. During instrumentation, 1 ml of
      2.5% NaOCl was used at each change of file. Samples were divided into 4 equal
      groups (n=20) according to the final irrigation activation technique: group 1,
      apical negative pressure (ANP) (EndoVac); group 2, manual dynamic agitation
      (MDA); group 3, passive ultrasonic irrigation (PUI); and group 4, needle
      irrigation (NI). Root canals were split longitudinally and subjected to scanning
      electron microscopy. The presence of smear layer at coronal, middle and apical
      levels was evaluated by superimposing 300-MUm square grid over the obtained
      photomicrographs using a four-score scale with X1,000 magnification. RESULTS:
      Amongst all the groups tested, ANP showed the overall best smear layer removal
      efficacy (p < 0.05). Removal of smear layer was least effective with the NI
      technique. CONCLUSION: ANP (EndoVac system) can be used as the final irrigation
      activation technique for effective smear layer removal in curved root canals.

PMID- 24910671
TI  - An In-vitro Comparison of Force Loss of Orthodontic Non-Latex Elastics.
AB  - OBJECTIVE: The amount and consistency of the applied forces to the tooth are
      important factors in tooth movements; therefore, the aim of this study was to
      compare the initial force and the force loss of three brands of elastics in 24
      hours. MATERIALS AND METHODS: In this in-vitro study sixty non-latex elastics
      (3/16 medium) from three companies (Forestadent, Dentaurum and Ortho Technology)
      were randomly selected. Two static tests were performed, the first in a dry
      environment to evaluate the initial force and the other performed in a wet
      environment (artificial saliva) to evaluate the force loss in 24 hours. The
      Universal testing machine measured the forces after stretching the elastics to
      three times the lumen diameter. Data were analyzed by repeated measures ANOVA,
      One-way ANOVA, Tukey-HSD, Paired samples test, and one sample test. RESULTS: The
      difference between the brands was significant (p=0.002). Force loss was observed
      in all samples; 4-7.5% force loss occurred after one hour and 19-38% force loss
      occurred after 24 hours. The average initial force of Forestadent and Ortho
      Technology was significantly higher than marketed forces (p<0.001), but the
      initial force of Dentaurum elastics was similar to the marketed force.
      CONCLUSION: The force loss over 24 hours time period was
      Forestadent>Dentaurum>Ortho-Technology. According to the initial force and force
      loss percentage it is suggested to replace the non-latex elastics several times a
      day.

PMID- 24910672
TI  - An in vivo comparison of two diagnostic methods in secondary caries detection.
AB  - OBJECTIVE: The aim of this study was to compare the level of agreement between
      four operators with different levels of experience for two methods of detecting
      secondary enamel and dentin carious lesions in composite restored teeth.
      MATERIALS AND METHODS: Sixty teeth of 40 patients with with secondary carious
      lesions in the composite resin were selected. The teeth were examined by two
      methods; visual inspection and a laser fluorescence device (DIAGNO dent pen 2190)
      by four operators including an undergraduate student, a dentist with 5 years of
      clinical experience, a general dentist with 12 years of clinical experience and
      an oral and maxillofacial radiologist. Cohen's kappa statistic was applied in
      order to assess the agreement between the diagnoses performed by the four
      operators with each diagnostic method. RESULTS: The diagnosis performed by
      different operators achieved an excellent agreement with high ICC. CONCLUSION:
      DIAGNOdent can be a useful device for secondary caries detection in posterior
      teeth as an adjunct to visual examination.

PMID- 24910673
TI  - Effect of Anticipatory Guidance Presentation Methods on the Knowledge and
      Attitude of Pregnant Women Relative to Maternal, Infant and Toddler's Oral Health
      Care.
AB  - OBJECTIVE: The prenatal period is the best time for health interventions. The aim
      of this study was to evaluate the effects of different methods of anticipatory
      guidance presentation on the change of knowledge and attitude of pregnant women
      regarding oral healthcare in the mother, infant and toddler. MATERIALS AND
      METHODS: In this quasi-experimental study, 90 pregnant women attended one health
      center in Zahedan, Iran; they were divided into direct intervention, indirect
      intervention and control groups. A self-reported questionnaire was completed
      before intervention. The guidance was presented to the direct intervention group,
      by PowerPoint and to the indirect group by pamphlet. Immediately after the
      intervention, the questionnaire was completed by intervention groups and two
      months later by all participants. Difference in the scores at start and end was
      calculated. Mann-Whitney, Kruskal-Wallis with Dunn's post hoc and Friedman with K
      W post-hoc tests were used for statistical analysis. The data was analyzed using
      SPPS version 19 software at a significance level of 0.05. RESULTS: The change in
      scores of knowledge relevant to maternal, infant and toddler's oral health and
      attitude toward maternal oral healthcare had significant differences in the three
      studied groups (P>0.05), The changes of scores in the four mentioned variables in
      the intervention groups were significantly higher than controls. In comparison
      between the intervention groups, the change in score of knowledge about maternal
      oral healthcare was significantly higher in the direct intervention group
      (P=0.023). CONCLUSION: Anticipatory guidance presentation led to change in the
      score of knowledge about maternal, infant and toddler's oral health and attitude
      towards maternal oral health in comparison to no presentation. The direct
      presentation had superiority over indirect in increasing knowledge about maternal
      oral healthcare.

PMID- 24910674
TI  - Residual Antimicrobial Activity of MTAD((r)) in Human Dentin After Obturation
      with Gutta-Percha/AH26 and Resilon/RealSeal SE at Different Time Intervals; An Ex
      Vivo Study.
AB  - OBJECTIVES: To eliminate microorganisms that are responsible for pulpal and
      periapical infections and to prevent reinfection of the root canal system an
      effective chemomechanical preparation by irrigants with sustained antimicrobial
      activity is beneficial. Hereby, we evaluated the residual antibacterial activity
      of MTAD after canal obturation at different time intervals. MATERIALS AND
      METHODS: A total of 120 human single-canalled anterior teeth were selected. The
      root canals were instrumented to a standardized apical size. Among all, 90 teeth
      received final irrigation with MTAD and were divided into three groups according
      to their obturation materials; i.e. gutta-percha/AH26, Resilon/RealSeal SE and
      positive controls. All these groups were divided into three 1-, 3- and 6-week
      time interval subgroups. Thirty teeth as negative control had no final irrigation
      with MTAD, but were obturated with gutta-percha/AH26 or Resilon/RealSealSE.
      Dentin powder was prepared after 1, 3 and 6 weeks. Dentin powder was exposed to
      Enterococcus faecalis for 24h and then cultured. Colony Forming Unit (CFU) was
      counted. RESULTS: Residual antimicrobial activity of MTAD in the teeth obturated
      with guttapercha/AH26 was significantly higher than the teeth obturated with
      Resilon/RealSeal SE (p<0.001). It also showed a time dependent decrease in MTAD
      antimicrobial activity for all groups. The highest antimicrobial activity of MTAD
      was found in the 1-week positive control and 1-week gutta-percha/AH26 specimens.
      The lowest antimicrobial activity of MTAD was found in 6-week Resilon/RealSeal SE
      samples and then the negative controls. CONCLUSION: MTAD had antimicrobial
      activity even at the sixth week, although it had a time-dependent decrease.
      Resilon/Epiphany SE significantly decreased antimicrobial activity of MTAD at all
      time points.

PMID- 24910675
TI  - Immunohistochemical pattern of pleomorphic adenoma, polymorphous low grade
      adenocarcinoma and adenoid cystic carcinoma in minor salivary glands.
AB  - OBJECTIVE: To study the immunohistochemical pattern of CD 117, glial fibrillary
      acidic protein (GFAP), smooth muscle actin (SMA) and CD 43 in pleomorphic adenoma
      (PA), adenoid cystic carcinoma (AdCC) and polymorphous low grade adenocarcinoma
      (PLGA) of minor salivary glands. MATERIALS AND METHODS: Twenty cases of PA, 20
      cases of AdCC and 10 cases of PLGA were retrieved from record files along with
      their paraffin blocks at Armed Forces Institute of Pathology, Pakistan. New
      histological diagnosis was made on freshly prepared H&E sections followed by
      application and analysis of immunostains. RESULTS: The mean age of the patients
      was 44 +/- 15 (mean SD) (range; 17-86) years. There were 26 male and 24 female
      patients with a male to female ratio of 1.08:1. Fourteen cases of PA, 14 cases of
      AdCC and 6 cases of PLGA were positive for CD117. In case of GFAP, only 9 cases
      of AdCC and 3 cases of PLGA were positive; however, 16 cases of PA were also
      positive. Twelve cases of AdCC and 7 cases of PA were positive for SMA and half
      of the PLGA cases were also reactive. Nonetheless, the least expression was seen
      in case of CD 43, where only five cases of AdCC were positive. Six cases of PA
      and three cases of PLGA were also positive. CONCLUSION: Our results suggest that
      the use of GFAP, SMA, CD 117 and CD 43 as an adjunct to histological examination
      is not helpful in differentiating PA, AdCC and PLGA from one another.

PMID- 24910676
TI  - Evaluation of genotoxicity in patients subjected to panoramic radiography by
      micronucleus assay on epithelial cells of the oral mucosa.
AB  - OBJECTIVE: Radiography is one of the most valuable diagnostic tools used in
      comprehensive dental care. Although there is no safe level of radiation exposure,
      the possible risk associated with exposure to radiation, must be elucidated. To
      date, a variety of assays have been proposed to assess the mutagenic potential of
      genotoxicants; however, these methods are typically laborious and time consuming.
      The aim of the present study was to evaluate the possible genotoxic effect of
      routinely used panoramic radiation exposure in exfoliated epithelial cells as
      measured by the formation of micronuclei and to compare the genotoxicity of X
      rays on keratinized epithelial gingival cells and the nonkeratinized buccal
      epithelial cells. MATERIALS AND METHODS: The study included 53 healthy
      individuals with a mean age of 25.21 +/-12.67 years. Specimens of exfoliated
      epithelial cells were collected from patients subjected to panoramic radiography
      before and 10 days after radiation exposure. The cells were stained with Giemsa
      and evaluated for micronuclei by scoring 1000 cells per slide. RESULTS: In our
      study, the genotoxic effect of radiation exposure from panoramic radiography
      showed a statistically significant increase in the MN frequency in buccal
      epithelial cells. A significant correlation was observed between the age of the
      subjects and micronuclei, although no such correlation was found between gender
      and micronuclei count. CONCLUSION: MN test serves as a simple biomarker
      indicating the direct exposure to DNA damaging agents such as ionizing radiation,
      emphasizing great sensitivity even for exposure to low doses during radiation
      screening. Thus, panoramic dental radiography should be cautiously used only when
      necessary.

PMID- 24910677
TI  - Monomer release from nanofilled and microhybrid dental composites after
      bleaching.
AB  - OBJECTIVE: The aim of this study was to assess the effect of bleaching on elution
      of monomers from nanofilled and microhybrid composites. MATERIALS AND METHODS: 80
      samples (5mm diameter and 3mm thickness) of each composite were prepared. After
      curing, half of them were randomly polished. Each group was divided into 8
      subgroups and immersed in water or 10%, 20% and 30% H2O2 for 3 or 8 hours. Eluted
      Bis-GMA (Bis-phenol A Glycidyl Dimethacrylate), TEGDMA (Triethyleneglycol
      Dimethacrylate), UDMA (Urethane Dimethacrylate) and BisEMA (Bis-phenol A
      ethoxylate Dimethacrylate) were quantified by high performance liquid
      chromatography and the results were analyzed by univariate ANOVA and t-test
      (P<0.05). RESULTS: Bleach significantly increased the overall release of monomers
      (P<0.001); TEGDMA was released more than Bis-GMA (P<0.001). Supreme released more
      TEGDMA compared to Z250 (P<0.001). Bleaching increased the release of this
      monomer (P<0.001). Increasing both the concentration of H2O2, and the immersion
      time, increased the release of TEGDMA (P<0.001). Polishing had no effect on
      release of this monomer (P=0.952). Supreme released more Bis-GMA than Z250
      (P=0.000). The more concentrated H2O2 caused more elution of Bis-GMA (P= 0.003);
      while the effect of immersion time was not significant (P=0.824). Polishing
      increased the release of Bis-GMA (P=0.001). Neither the type of composite nor
      Bleaching had any effect on release of UDMA (P=0.972) and (P=0.811) respectively.
      Immersion duration increased the release of UDMA (P=0.002), as well as polishing
      (P=0.024). CONCLUSION: Bleaching increased the release of monomers. Nanofilled
      composites released more monomer than the microfilled.

PMID- 24910678
TI  - Orthodontic research output from iran in international and national journals.
AB  - OBJECTIVE: The number of scientific papers is a conventional metric to measure a
      country's research performance in a particular area. The aim of this survey was
      to demonstrate statistical information about orthodontic research published in
      international and national journals. MATERIALS AND METHODS: Pubmed as an
      international and IranMedex and SID as national databases were searched
      between1997 and 2012. The keyword searching method was used in English and
      Persian. Abstracts were reviewed and unrelated articles were omitted. Data were
      obtained and transferred to Microsoft Excel to survey the scintometric
      indicators. RESULTS: According to the defined criteria, a total of 733 papers
      were found showing a considerable increase. Five hundred papers (68.2%) were
      published in domestic journals, and 233 (31.8%) were published in PubMed indexed
      journals. Most of the orthodontic articles originated from Shahid Beheshti
      University of Medical Sciences (22.9%). The Journal of Dental School, Shahid
      Beheshti University of Medical Sciences published most of the national papers
      (27.8%) and the Australian Orthodontic Journal published the majority of
      international papers (9.9%) In terms of study design, 52.5% of the articles were
      observational and 39.4% were interventional. CONCLUSION: Orthodontic research
      production in Iran has made significant strides in the recent years and
      researchers should focus on the quality of the study in this field in order to
      apply research production in evidence base dentistry.

PMID- 24910679
TI  - Fixed versus Removable Appliance for Palatal Expansion; A 3D Analysis Using the
      Finite Element Method.
AB  - OBJECTIVE: Several appliances have been used for palatal expansion for treatment
      of posterior cross bite. The purpose of this study was to evaluate the stress
      induced in the apical and crestal alveolar bone and the pattern of tooth
      displacement following expansion via removable expansion plates or fixed-banded
      palatal expander using the finite element method (FEM) analysis. MATERIALS AND
      METHODS: Two 3D FEM models were designed from a mesio-distal slice of the maxilla
      containing the upper first molars, their periodontium and alveolar bone. Two
      palatal expanders (removable and fixed) were modeled. The models were designed in
      SolidWorks 2006 and then transferred to ANSYS Workbench. The appliance halves
      were displaced 0.1 mm laterally. The von Mises stress in the apical, crestal, and
      PDL areas and also the vertical displacement of the cusps (palatal and buccal)
      was were evaluated. RESULTS: The total PDL stress was 0.40003 MPa in the
      removable appliance (RA) model and 4.88e-2 MPa in the fixed appliance (FA) model
      and the apical stress was 9.9e-2 and 1.17e-2 MPa, respectively. The crestal
      stress was 2.99e-1 MPa in RA and 7.62e-2 MPa in the FA. The stress in the
      cortical bone crest was 0.30327 and 7.9244e-2 MPa for RA and FA, respectively and
      3.7271 and 7.4373e-2 MPa in crestal area of spongy bone, respectively. The
      vertical displacement of the buccal cusp and palatal cusp was 1.64e-2 and 5.90e-2
      mm in RA and 1.05e-4 and 1.7e-4 mm in FA, respectively. CONCLUSION: The overall
      stress as well as apical and crestal stress in periodontium of anchor teeth was
      higher in RA than FA; RA elicited higher stress in both cortical and spongy bone.
      The vertical displacement of molar cusps was more in removable than fixed palatal
      expander model.

PMID- 24910680
TI  - Effect of cyclic loading on bond strength of fiber posts to root canal dentin.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of cyclic loading on
      the bond strength of quartz fiber posts to root canal dentin after different
      surface treatments of different regions of root canal dentin. MATERIALS AND
      METHODS: Forty-eight single-rooted human teeth were selected. Post spaces were
      prepared and then the teeth were divided into four groups: G1: no treatment
      (control); G2: irrigation with a chemical solvent; G3: etching with 37%
      phosphoric acid; G4: treatment with ultrasonic file. The fiber posts were
      cemented using dual-cured resin cement. Half of the specimens were load-cycled
      (10000 cycles, 3 cycles/s) and the others did not undergo any load cycling. From
      each root, two slides measuring 1 mm in thickness were obtained from the apical
      and cervical regions. The push-out bond strength test was performed for each
      slice. Data were analyzed by using 3-way ANOVA and Tukey HSD tests. The fracture
      modes were evaluated under a stereomicroscope at *20. RESULTS: The effect of load
      cycling and surface treatment as the main factors and the interaction of main
      factors were not significant (P=0.734, P=0.180, and P=0.539, respectively). The
      most frequent failure mode under the stereomicroscope was adhesive. CONCLUSION:
      It appears that load cycling and surface treatment methods had no effect on the
      bond strength of fiber posts to root canal dentin, but it depended on the region
      of the root canal dentin.

PMID- 24910681
TI  - Sedative Effect of Oral Midazolam/Hydroxyzine versus Chloral Hydrate/Hydroxyzine
      on 2-6 Year-Old Uncooperative Dental Patients: A Randomized Clinical Trial.
AB  - OBJECTIVE: Different drugs are used for conscious sedation in pediatric dentistry
      either single or in combination. This study assessed the comparative effect of
      midazolam/hydroxyzine and chloral hydrate/hydroxyzine on 2-6 year-old
      uncooperative children needing dental treatment. MATERIALS AND METHODS: A double
      blind cross-over randomized clinical trial was designed and 16 children aged 2-6
      years with ASA1 status who were judged with negative to definitely negative
      behavior (according to Frankl) were chosen. Cases were divided randomly into two
      groups. The first group received midazolam/hydroxyzine (MH) at the first visit
      while the second group received chloral hydrate/hydroxyzine (CHH) as the first
      medication. Both groups received the other regimen at the second visit. Midazolam
      0.5mg/kg and chloral hydrate 50mg/kg with 1mg/kg hydroxyzine were administered.
      Cases were subsequently assessed for sedation and then dental treatment was
      performed. Blood oxygen saturation (SpO2) and pulse rate (PR) were measured
      before and after drug administration, as well as during and after dental
      treatment. The Houpt scale was also used for the level of sedation before, during
      and after treatment. Data were analyzed using Wilcox-on signed rank test and the
      paired t-test. RESULTS: Sedative success rate was 64.3% in cases of MH and 33.3%
      in CHH. The difference between groups was significant (P=0.046). The success rate
      was significantly different between groups at different measurement stages as
      well (P<0.05). No difference was found on the child's behavior scale based on the
      type of drugs used first; this indicates no carry-over effect. Comparing the PR
      and SpO2 values at different readings showed no significant differences.
      CONCLUSION: Midazolam/hydroxyzine showed a significantly higher sedative effect
      than chloral hydrate/hydroxyzine in this study.

PMID- 24910682
TI  - Magnet retained cheek plumper in complete denture esthetics: a case report.
AB  - This clinical report describes a technique to improve support for sunken cheeks
      using magnet retained detachable acrylic cheek plumpers. The new generation of
      magnets with improved technology provides sufficient denture retention for
      clinical application. However, further follow-up may be necessary to ascertain
      the long-term usefulness of the magnet-retained prosthesis, because of corrosion
      and further loss of magnetism. 

PMID- 24910683
TI  - Single Tooth Replacement Using InCeram Resin Bonded Fixed Partial Denture: A
      Clinical Report.
AB  - This clinical report describes a treatment option for replacement of a missing
      mandibular anterior tooth using InCeram resin bonded fixed partial denture
      (RBFPD). The conventional approach for replacing mandibular incisors dictates the
      placement of either a conventional porcelain-fused-to-metal (PFM) bridge,
      Maryland bridge, or fiber-reinforced composite veneer bridge and several
      appearance-related disadvantages have been reported in the use of a prosthesis
      that incorporates a metal substructure. The InCeram bridge is a minimally
      invasive restoration and eliminates undesirable incisal graying frequently
      observed in metal RBFPDs. This method was successfully clinically applied to
      overcome shortcomings of other approaches that may require a minimal invasive
      technique to preserve lasting sound tooth structure. 

PMID- 24910684
TI  - C-shaped canal in maxillary first molars: a case report.
AB  - C-shaped configuration in the upper maillary first molar is an extremely rare
      appearance (0.12%). This case reports management of the tooth with such a
      configuration as well as depiction of its internal morpholgy and external
      morphology through spiral computed tomography and dentascan in the contralateral
      tooth with similar morphology. After careful clinical observation and
      confirmation through spiral computed tomography, it was concluded that the teeth
      had Melton category I configuration with fused roots. 

PMID- 24910685
TI  - Mandibular first molar with a radix entomolaris: an endodontic dilemma.
AB  - It is known that the mandibular first molar can display significant anatomical
      variations namely the number of root canals, the number of roots and morphology.
      Mandibular molars may sometimes have an additional root located lingually (the
      radix entomolaris) or buccally (the radix paramolaris). If encountered, an
      awareness and understanding of this unusual root and its canal morphology can
      contribute to the successful outcome of root canal treatment. This case report
      discusses endodontic treatment of a mandibular first molar with a radix
      entomolaris, which is a rare entity and poses as an endodontic dilemma for the
      clinician with respect to diagnosis and subsequent treatment. Clinicians should
      be aware of these unusual root morphologies in the mandibular first molar which
      needs strategic treatment as unfilled canals remain a nidus for infection and can
      compromise treatment outcome. 

PMID- 24910686
TI  - Effects of carbonated soft drink consumption on orthodontic tooth movements in
      rats.
AB  - OBJECTIVE: The aim of this animal study was to evaluate the possible effects of
      Carbonated Soft Drink consumption on the rate of orthodontic tooth movement in
      rats. MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats were
      randomly divided into two experimental groups and one control group. In the
      experimental groups (A&B), the water in the dietary regimen was replaced with
      soft drinks (Fanta(r) in group A and Cola(r) in group B) two weeks before
      placement of orthodontic appliances. Then 5-mm nickel-titanium closed-coil
      springs were placed between the maxillary right first molars and first incisors
      under general anesthesia. This regimen continued for two weeks more and animals
      drank soft drink ad libitum. At the end of the experimental period, the rats were
      sacrificed, and interproximal tooth movements were measured. RESULTS: The mean
      amounts of tooth movement were 0.19mm in group A, 0.22mm in group B and 0.37mm in
      group C. Statistical analysis with analysis of variance (ANOVA) test showed
      significant differences between all groups. The least movement occurred in group
      A that had received Fanta(r) drink. CONCLUSION: CSDs consumption decreases the
      rate of orthodontic tooth movement. The role of soft drinks in decreasing tooth
      movement might be related to its effects on bone metabolism.

PMID- 24910687
TI  - The effect of remin pro and MI paste plus on bleached enamel surface roughness.
AB  - OBJECTIVE: The growing demand for enhanced esthetic appearance has led to great
      developments in bleaching products. The exposure of hard tissues of the tooth to
      bleaching agents can affect the roughness of the enamel surface. The freshly
      bleached enamel surface exposed to various surface treatments such as fluoride
      and other remineralizing agents have been assessed in this study. The aim of this
      experimental study was to compare the effect of Casein Phosphopeptide-Amorphous
      Calcium Phosphate with Fluoride (MI Paste Plus) and Remin Pro on the enamel
      surface roughness after bleaching. MATERIALS AND METHODS: Thirty enamel samples
      of sound human permanent molars were prepared for this study. After initial
      roughness measurement with profilometer, the samples were exposed to 37%
      carbamide peroxide bleaching agent 20 minutes twice, and randomly divided into
      three groups of ten. In group 1, a CPP-ACPF containing paste (MI Paste Plus) and
      in group 2, Remin Pro were applied to the teeth during a 15 day period for 5
      minutes, twice a day. Samples of group 3 (control) were immersed in artificial
      saliva for 15 days. The roughness of all samples were measured at the beginning,
      after bleaching and after the study intervention and statistically analyzed.
      RESULTS: The surface roughness significantly increased in all groups following
      bleaching, and then it showed a decrease after application of both Remin Pro and
      CPP-ACPF in comparison to using bleaching agent (P<0.005). The surface roughness
      after using Remin Pro and CPP-ACPF was statistically similar to each other
      (P>0.05). CONCLUSION: There was no difference between surface roughness of MI
      Paste Plus and Remin Pro groups. Also the surface roughness was decreased
      compared to the initial enamel surface roughness.

PMID- 24910688
TI  - Assessment of Microshear Bond Strength: Self-Etching Sealant versus Conventional
      Sealant.
AB  - OBJECTIVE: Recently, self-etching fissure sealants have been introduced to reduce
      technical sensitivity; however, their efficacy should be assessed. The aim of
      this study was to assess of the microshear bond strength of self-etching and
      conventional fissure sealants. MATERIALS AND METHODS: Thirty non-carious third
      molars were randomly divided into three groups (N=10). Microcylinders of Concise
      fissure sealant were bonded to prepared buccal and lingual surfaces using the two
      following procedures. In the first group, phosphoric acid was used to prepare the
      substrate; whereas in group two, Concise was used in combination with Prompt L
      Pop. In group 3, a self-etching fissure sealant (Enamel Loc) was utilized per se.
      After 24 hours, the samples were subjected to 500 rounds of thermocycling and
      shear bond testing using a microtensile tester machine with a crosshead speed of
      0.5mm/min. Data were analyzed using one-way repeated measure ANOVA and Bonferroni
      Post HOC tests (SPSS version 16). RESULTS: THE MEAN AND STANDARD DEVIATION OF
      MICROSHEAR BOND STRENGTH OF THE GROUPS WERE AS FOLLOWS: Group 1: Concise+ etching
      (14.59 +/- 1.19 MPa), Group 2: Concise+Prompt L-Pop (12.86 +/- 1.98 MPa), and
      Group 3: Enamel Loc (5.59 +/- 0.72 MPa). One-way ANOVA revealed that all the
      differences were significant and the conventional sealant exhibited the highest
      mean bond strength. CONCLUSION: Conventional sealant using phosphoric acid etch
      application prior to fissure sealant application demonstrated more bond strength
      in comparison with that of self-etch bonding and self-etch sealant.

PMID- 24910689
TI  - Biodentine versus Mineral Trioxide Aggregate versus Intermediate Restorative
      Material for Retrograde Root End Filling: An Invitro Study.
AB  - OBJECTIVE: The aim of this study was to evaluate the marginal adaptation of
      Biodentine in comparison with Mineral Trioxide Aggregate (MTA) and Intermediate
      Restorative Material (IRM), as a root end filling material, using Scanning
      Electron Microscopy (SEM). MATERIALS AND METHODS: Thirty permanent maxillary
      central incisors were chemo-mechanically prepared and obturated. Three
      millimetres of the root end were resected and 3mm retro cavity preparation was
      done using ultrasonic retrotips. The samples were randomly divided into three
      groups (n=10) and were restored with root end filling materials: Group I - MTA,
      Group II - Biodentine, Group III - IRM. The root ends were sectioned transversely
      at 1mm and 2mm levels and evaluated for marginal adaptation using SEM. The gap
      between dentin and retro filling material was measured at four quadrants. The
      mean gap at 1mm level and 2mm level from the resected root tip and combined mean
      were calculated. The data were statistically analyzed, using one-way ANOVA and
      Tukey's HSD post hoc test for intergroup analysis and paired t-test for
      intragroup analysis. RESULTS: The overall results showed no statistically
      significant difference between MTA and IRM but both were superior when compared
      to Biodentine. At 1mm level there was no statistically significant difference
      among any of the tested materials. At 2mm level MTA was superior to both IRM and
      Biodentine. CONCLUSION: In overall comparison, MTA and IRM were significantly
      superior when compared to Biodentine in terms of marginal adaptation, when used
      as retrograde filling material.

PMID- 24910690
TI  - Bond strength of composite resin to enamel: assessment of two ethanol wet-bonding
      techniques.
AB  - OBJECTIVE: Ethanol wet-bonding (EWB) technique has been stated to decrease
      degradation of resin-dentin bond. This study evaluated the effect of two EWB
      techniques on composite resin-to-enamel bond strength. MATERIALS AND METHODS:
      Silicon carbide papers were used to produce flat enamel surfaces on the buccal
      faces of forty-five molars. OptiBond FL (OFL) adhesive was applied on enamel
      surfaces in three groups of 15 namely: Enamel surface and OFL (control);Protocol
      1 of the EWB technique: absolute ethanol was applied to water-saturated acid
      etched enamel surfaces for 1 minute before the application of ethanol-solvated
      hydrophobic adhesive resin of OFL 3 times;Protocol 2: progressive ethanol
      replacement; water was gradually removed from the enamel matrix using ascending
      ethanol concentrations before OFL application. Composite build-ups were made and
      the specimens were stored for 24 hours at 37 degrees C and 100% relative
      humidity. Shear bond strength test was performed using a universal testing
      machine at 1 mm/min crosshead speed. Fracture patterns were evaluated
      microscopically. Data were analyzed with one-way ANOVA and Fisher's exact test
      (alpha=0.05). RESULTS: There were no significant differences in bond strength
      between the groups (P=0.73). However, regarding failure patterns, the highest
      cohesive enamel fractures were recorded in groups 2 and 3. CONCLUSION: In this
      study, although both methods of EWB did not influence immediate bond strength of
      composite resin to enamel, the majority of failure patterns occurred cohesively
      in enamel.

PMID- 24910691
TI  - Effect of acidic environment on dislocation resistance of endosequence root
      repair material and mineral trioxide aggregate.
AB  - OBJECTIVE: The aim of this study was to compare the effect of an acidic
      environment on dislocation resistance (push-out bond strength) of EndoSequence
      Root Repair Material (ERRM putty and ERRM paste), a new bioceramic-based
      material, to that of mineral tri-oxide aggregate (MTA). MATERIALS AND METHODS:
      One-hundred twenty root dentin slices with standardized canal spaces were divided
      into 6 groups (n = 20 each) and filled with tooth-colored ProRoot MTA (groups 1
      and 2), ERRM putty (groups 3 and 4), or ERRM paste (groups 5 and 6). The
      specimens of groups 1, 3, and 5 were exposed to phosphate buffered saline (PBS)
      solution (pH=7.4) and those of groups 2, 4, and 6 were exposed to butyric acid
      (pH= 4.4). The specimens were then incubated for 4 days at 37 degrees C. The push
      out bond strength was then measured using a universal testing machine. Failure
      modes after the push-out test were examined under a light microscope at *40
      magnification. The data for dislocation resistance were analyzed using the t-test
      and one-way analysis of variance. RESULTS: In PBS environment (pH=7.4), there
      were no significant differences among materials (P=0.30); but the mean push-out
      bond strength of ERRM putty was significantly higher than that of other materials
      in an acidic environment (P<0.001). Push-out bond strength of MTA and ERRM paste
      decreased after exposure to an acidic environment; whereas ERRM putty was not
      affected by acidic pH. The bond failure mode was predominantly cohesive for all
      groups except for MTA in an acidic environment; which showed mixed bond failure
      in most of the specimens. CONCLUSION: The force needed for dislocation of MTA and
      ERRM paste was significantly lower in samples stored in acidic pH; however, push
      out bond strength of ERRM putty was not influenced by acidity.

PMID- 24910692
TI  - Therapeutic Effects of "Ibuprofen, Diphenhydramine and Aluminium MgS" on
      Recurrent Aphthous Stomatitis: A Randomized Controlled Trial.
AB  - OBJECTIVE: Recurrent aphthous stomatitis (RAS) is the most common and painful
      oral inflammatory lesion with an unknown etiology. This study aims to determine
      the therapeutic effects of ibuprofen, diphenhydramine and aluminum magnesium
      simethicone (AlMgS) syrup on reducing oral aphthous ulcer pain. MATERIALS AND
      METHODS: Thirty-one patients with RAS participated in this double-blind clinical
      trial. Subjects were randomly divided into two groups. The control group (n=14)
      received drug mixture as drug A (diphenhydramine and AlMgS) and the case group
      (n=17) received drug B (ibuprofen, diphenhydramine and AlMgS). Drugs were
      topically applied on ulcers by the patients three times a day for 3 days.
      Patients were re-examined for the symptoms on the fourth day following their
      first visits using VAS (Visual Analogue Scale) tool. Statistical analysis was
      performed using paired t-test, independent t-test and chi-square test. RESULTS:
      The mean of pain reduction was 3.17+/-2 (P<0.001) and 3.82+/-1.79 (P<0.001) in
      the case and control group, respectively. The difference in pain reduction
      between both groups was not statistically significant. In addition, no
      significant difference was detected between the two groups regarding the duration
      of pain or burning sensation (P=0.57). CONCLUSION: The results of this study
      demonstrate that in comparison with diphenhydramine and AlMgS syrup, the studied
      mixture did not effectively reduce the level of pain, duration and burning
      sensation.

PMID- 24910693
TI  - Assessment of Tooth Preparation via Er:YAG Laser and Bur on Microleakage of
      Dentin Adhesives.
AB  - OBJECTIVE: Microleakage can be responsible for tooth hypersensitivity, secondary
      caries, and the possibility of pathological pulp alterations in restored teeth.
      Recently, alternative methods for tooth preparation such as laser irradiation
      have been studied; but there are limited studies on primary teeth. The aim of
      this in vitro study was to compare the degree of microleakage of composite
      restorations prepared by Er:YAG laser and conventional bur preparation with two
      adhesive systems in primary teeth. MATERIALS AND METHODS: Eighty primary canine
      teeth were randomly divided into 4 groups. Class V cavities were prepared by
      Er:YAG laser or diamond bur on buccal surface. The groups were as follows:
      group1: High speed drill + self-etching adhesive Adper Prompt-L-Pop, group 2:
      Er:YAG laser + etch & rinse adhesive Adper Single Bond, group 3: High speed drill
      + Adper Single Bond, group 4: Er:YAG laser + Adper Prompt-L-Pop. Cavities were
      restored with Filtek Z250 composite resin. Then all of the specimens were
      polished, thermocycled, immersed in 2% methylene blue solution and sectioned
      longitudinally. Degree of microleakage was evaluated by two evaluators who
      assigned the micrleakage score (0 to 3). The original data were analyzed by the
      Kruskal-Wallis and Dunn's tests. RESULTS: There were significant differences
      between bur-prepared cavities in the Adper Single Bond and other groups. There
      were no statistically significant differences between other groups. CONCLUSION:
      Laser-prepared cavities showed higher microleakage scores than cavities prepared
      with diamond bur with etch and rinse adhesive system. No significant difference
      was revealed between the laser and bur-prepared cavities using self-etch primers.

PMID- 24910694
TI  - Bond strength and interfacial morphology of different dentin adhesives in primary
      teeth.
AB  - OBJECTIVE: To evaluate the interfacial morphology and the bond strength produced
      by the three-step, two-step and single-step bonding systems in primary teeth.
      MATERIALS AND METHODS: Occlusal surfaces of 72 extracted human deciduous teeth
      were ground to expose the dentin. The teeth were divided into four groups: (a)
      Scotchbond Multipurpose (3M, ESPE), (b) Adh Se (Vivadent), (d) OptiBond All-in
      One (Kerr) and (e)Futurabond NR (VOCO, Cuxhaven, Germany). The adhesives were
      applied to each group following the manufacturer's instructions. Then, teeth from
      each group were divided into two groups: (A) For viewing interfacial morphology
      (32 teeth), with 8 teeth in each group, and (B) For measurement of bond strength
      (40 teeth), with 10 teeth in each group. All the samples were prepared for
      viewing under SEM. The statistical analysis was done using SPSS version 15.0
      software. RESULTS: Observational measurement of tag length in different adhesives
      revealed that Scotchbond had the most widely spread values with a range from
      12.20 to 89.10MUm while OptiBond AIO had the narrowest range (0 to 22.50). The
      bond strength of Scotchbond Multipurpose was significantly higher (7.4744+/
      1.88763) (p<0.001) as compared to Futurabond NR (3.8070+/-1.61345), Adhe SE
      (4.4478 +/- 1.3820) and OptiBond-all-in-one (4.4856+/-1.07925). CONCLUSION: The
      three-step bonding system showed better results as compared to simplified studied
      bonding systems.

PMID- 24910696
TI  - Effects of 15% carbamide peroxide and 40% hydrogen peroxide on the microhardness
      and color change of composite resins.
AB  - OBJECTIVE: The aim of this study was to determine the effects of 40% hydrogen
      peroxide and 15% carbamide peroxide on microhardness and color change of a
      silorane-based composite resin in comparison with two methacrylate-based
      composites. MATERIALS AND METHODS: Fifty-four disc-shaped specimens (A3 shade)
      were fabricated of Filtek P90 (P90), Filtek Z350XT Enamel (Z350) and Filtek Z250
      (Z250) (3MESPE) (n=18). The samples of each composite were randomly divided into
      three subgroups of 6. The control subgroups were immersed in distilled water; the
      test groups were exposed to Opalescence Boost (OB) once; and Opalescence PF (OP)
      (Ultradent) for two weeks. Vickers microhardness testing and a spectrophotometric
      analysis of the color of samples were performed before and after each
      intervention. RESULTS: The baseline microhardness of P90 was significantly lower
      than that of the other two composites (P=0.001), but no difference was found
      between Z250 and Z350 in this respect (P=0.293). Bleaching treatments
      significantly decreased the microhardness of Z250 and Z350 (P< 0.001), but no
      change was observed in P90 test and control subgroups (P> 0.05). No significant
      difference was detected between the two types of bleaching (P>0.05). After
      bleaching with OB, DeltaE value was measured to be 3.12(1.97), 3.31(1.84) and
      3.7(2.11) for P90, Z250 and Z350, respectively. These values were 5.98(2.42),
      4.66(2.85) and 4.90(2.78) after bleaching with OP with no significant difference.
      CONCLUSION: Bleaching decreased the microhardness of methacrylate-based but not
      silorane-based composites. Although no significant differences were found in
      DeltaE of composites, DeltaE of all groups did not remain in the clinically
      acceptable range after bleaching except for P90 after bleaching with 40% H2O2
      (DeltaE < 3.3).

PMID- 24910695
TI  - Effect of master apical file size and taper on irrigation and cleaning of the
      apical third of curved canals.
AB  - OBJECTIVE: Canal preparation generates a substantial amount of debris and smear
      layer (SL). The size and taper of the Master Apical File (MAF) affects on
      penetration of irrigants and subsequently canal cleaning efficacy. The aim of
      this study was to evaluate the effect of MAF size and taper on penetration of
      irrigants to the apical third of curved mesiobuccal (MB) canals of mandibular
      first molars. MATERIALS AND METHODS: Eighty-nine human mandibular first molars
      were divided into one control group (n=5) without rotary instrumentation and 6
      experimental groups (n=14 each) that were prepared with the following RaCe rotary
      files as MAF: 25.04 (group1), 25.06 (group 2), 30.04 (group 3), 30.06 (group 4),
      35.04 (group 5) and 35.06 (group 6). All the experimental groups were rinsed with
      2 ml of 17 % EDTA followed by 2 ml of 5.25% NaOCl. Debridement of the MB canals
      was evaluated using scanning electron microscope (SEM). The data were
      statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests (P<0.05).
      RESULTS: Group 6 (MAF=35.06) showed 100% acceptable debridement. This rate was
      92.9% for MAF=35.04. In group 4 (MAF=30.06) smear layer (SL) was removed in the
      three-forth of the samples and debris was removed in 92.9% of them. Acceptable
      debridement was not achieved in most samples of groups 1 and 2 (25.04 and 25.06,
      respectively) and the mentioned two groups had statistically significant
      difference in this respect with the other groups (P<0.05). CONCLUSION: Based on
      this study, 30.06 may be considered as the minimum MAF size for acceptable
      debridement.

PMID- 24910697
TI  - Implant Surface Temperature Changes during Er:YAG Laser Irradiation with
      Different Cooling Systems.
AB  - OBJECTIVE: Peri-implantitis is one of the most common reasons for implant
      failure. Decontamination of infected implant surfaces can be achieved effectively
      by laser irradiation; although the associated thermal rise may cause irreversible
      bone damage and lead to implant loss. Temperature increments of over 10oC during
      laser application may suffice for irreversible bone damage. PURPOSE OF STUDY: The
      purpose of this study was to evaluate the temperature increment of implant
      surface during Er:YAG laser irradiation with different cooling systems. MATERIALS
      AND METHODS: Three implants were placed in a resected block of sheep mandible and
      irradiated with Er:YAG laser with 3 different cooling systems namely water and
      air spray, air spray alone and no water or air spray. Temperature changes of the
      implant surface were monitored during laser irradiation with a K-type
      thermocouple at the apical area of the fixture. RESULTS: In all 3 groups, the
      maximum temperature rise was lower than 10 degrees C. Temperature changes were
      significantly different with different cooling systems used (P<0.001).
      CONCLUSION: Based on the results, no thermal damage was observed during implant
      surface decontamination by Er:YAG laser with and without refrigeration. Thus,
      Er:YAG laser irradiation can be a safe method for treatment of periimplantitis.

PMID- 24910698
TI  - The effect of remin pro and MI paste plus on bleached enamel surface roughness.
AB  - OBJECTIVE: Increased number of adult patients requesting orthodontic treatment
      result in bonding bracket to ceramic restorations more than before. The aim of
      this study was to evaluate and compare the shear bond strength of orthodontic
      brackets bonded to two types of ceramic bases with conventional orthodontic
      bonding resin and a new nano-filled composite resin. MATERIALS AND METHODS:
      Twenty four feldespathic porcelain and 24 lithium disilicate ceramic disks were
      fabricated. All of the samples were conditioned by sandblasting, hydrofluoric
      acid and silane. Maxillary incisor metal brackets were bonded to half of the
      disks in each group by conventional orthodontic bonding resin and the other half
      bonded with a nano-filled composite. The samples then were thermocycled for 2000
      cycle between 5-55 degrees  C. Shear bond strength was measured and the mode of
      failure was examined. Randomly selected samples were also evaluated by SEM.
      RESULTS: The lowest bond strength value was found infeldespathic ceramic bonded
      by nano-filled composite (p<0.05). There was not any statistically significant
      difference between other groups regarding bond strength. The mode of failure in
      the all groups except group 1 was cohesive and porcelain damages were detected.
      CONCLUSION: Since less damages to feldspathic porcelain was observed when the
      nano-filled composite was used to bond brackets, the use of nano-filled composite
      resins can be suggested for bonding brackets to feldspathic porcelain
      restorations.

PMID- 24910699
TI  - Pomegranate juice (punica granatum): a new storage medium for avulsed teeth.
AB  - OBJECTIVE: There is evidence indicating that pomegranate juice contains many of
      the essential properties necessary to retain cell viability and cell
      proliferation. These properties indicate that pomegranate juice is a suitable
      storage medium for avulsed teeth. However, this idea has not yet been tested. In
      this study, the capacity of pomegranate juice (PJ) as a storage medium for
      retaining avulsed teeth was evaluated. MATERIALS AND METHODS: PDL fibroblasts
      were obtained from healthy human premolars and cultured in Dulbecco's Modified
      Eagle's Medium (DMEM). Cultured cells were subjected to different concentrations
      of pomegranate juice (PJ), 1% Hank's balanced salt solution (HBSS) and tap water
      for 1, 3, 6 and 24 hours. PDL cell viability was assessed by the neutral red
      uptake assay. RESULTS: The results indicated that 7.5% PJ was the most effective
      solution for maintaining PDL cell viability amongst all the experimental
      solution's and time intervals (P<0.05). The results also showed that 1% PJ was as
      effective as HBSS for maintaining PDL cell viability. The amount of cell
      viability increased with increasing concentration of PJ at all time intervals
      (P<0.001). This effect is suggestive of the proliferative potential of PJ
      solution. CONCLUSION: In conclusion, PJ can be recommended as a suitable
      transport medium for avulsed teeth.

PMID- 24910700
TI  - Effects of different lasers and particle abrasion on surface characteristics of
      zirconia ceramics.
AB  - OBJECTIVE: The aim of this study was to assess the surface of yttrium-stabilized
      tetragonal zirconia (Y-TZP) after surface treatment with lasers and airborne
      particle abrasion. MATERIALS AND METHODS: First, 77 samples of presintered
      zirconia blocks measuring 10 * 10 * 2 mm were made, sintered and polished. Then,
      they were randomly divided into 11 groups (n=7) and received surface treatments
      namely, Er:YAG laser irradiation with output power of 1.5, 2 and 2.5 W, Nd:YAG
      laser with output power of 1.5, 2 and 2.5 W, CO2 laser with output power of 3, 4
      and 5 W, AL2O3 airborne-particle abrasion (50MU) and no treatment (controls).
      Following treatment, the parameters of surface roughness such as Ra, Rku and Rsk
      were evaluated using a digital profilometer and surface examination was done by
      SEM. RESULTS: According to ANOVA and Tukey's test, the mean surface roughness
      (Ra) after Nd:YAG laser irradiation at 2 and 2.5 W was significantly higher than
      other groups. Roughness increased with increasing output power of Nd:YAG and CO2
      lasers. Treated surfaces by Er:YAG laser and air abrasion showed similar surface
      roughness. SEM micrographs showed small microcracks in specimens irradiated with
      Nd:YAG and CO2 lasers. CONCLUSION: Nd:YAG laser created a rough surface on the
      zirconia ceramic with many microcracks; therefore, its use is not recommended.
      Air abrasion method can be used with Er:YAG laser irradiation for the treatment
      of zirconia ceramic.

PMID- 24910701
TI  - Clinical Management of Glanzmann's Thrombasthenia: A Case Report.
AB  - Glanzmann's thrombasthenia (GT) is a rare, genetically inherited platelet
      disorder in which the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) complex is
      either deficient or, dysfunctional. The incidence is about 1 in 1,000,000. This
      case report deals with a 4 year-old girl diagnosed with GT presenting with dental
      caries and periapical lesions in the primary mandibular first molars. To provide
      the best care, an interdisciplinary approach was followed by a team consisting of
      pediatric dentists, pediatricians and anesthesiologists. Complete oral
      rehabilitation was planned under general anesthesia which included extractions,
      multiple esthetic restorations and space maintainers with the utmost care to
      prevent unwarranted bleeding. 

PMID- 24910702
TI  - Acetyl-L-Carnitine Supplementation During HCV Therapy With Pegylated Interferon
      alpha 2b Plus Ribavirin: Effect on Work Performance; A Randomized Clinical Trial.
AB  - BACKGROUND: The health status of employees with chronic hepatitis C has major
      implications for organizations and labour market. OBJECTIVES: To assess the
      effects of Acetyl-L-Carnitine administration on work productivity, daily
      activity, and fatigue in subjects with chronic hepatitis C treated with Pegylated
      Interferon-alpha2b and Ribavirin. PATIENTS AND METHODS: In this prospective,
      randomized, placebo controlled, double blind clinical trial, 30 subjects (Group
      A) with chronic hepatitis, received Pegylated-Interferon-alpha2b (1.5 mg/kg per
      week) plus Ribavirin and placebo, while 32 subjects (Group B) received the same
      dosage of Pegylated-Interferon-alpha2b plus Ribavirin plus 2g Acetyl-L-Carnitine
      twice per day, for 12 months. Work productivity loss, impairment in daily
      activities, presenteeism, absenteeism, have been assessed using the Work
      Productivity and Activity Impairment questionnaire. We also evaluated severity of
      fatigue, mental fatigue and physical fatigue. RESULTS: Significant difference
      were observed in physical fatigue, mental fatigue and severity of fatigue,
      aspartate aminotransferase, alanine aminotransferase, and viremia after 12 months
      treatment. In Group B we observed a significant decrease of presenteeism and
      daily activity impairment after 6 months, 12 months and at follow up. A
      significant increase of work productivity was observed after 12 months and at
      follow up. CONCLUSIONS: Office workers with chronic hepatitis C, treated with
      Pegylated-Interferon-alpha2b plus Ribavirin, had work performance loss. In
      subjects treated with Acetyl-L-Carnitine supplementation we observed increased
      daily activity and reduced presenteeism and fatigue. Acetyl-L-Carnitinegroup had
      a smaller reduction of productivity comparing to placebo group.

PMID- 24910703
TI  - Distribution of HCV genotypes in the populations of inmates in polish prison
      potulice and patients hospitalised in bydgoszcz.
AB  - BACKGROUND: According to many studies, one of the social groups with high rate of
      HCV infections are prisoners. OBJECTIVES: The aim of the study was to determine
      and compare the genotypes distribution among prisoners and patients of hospital.
      PATIENTS AND METHODS: HCV genotypes among prisoners (281 inmates) and patients of
      hospital (1415 patients) were determined in years 2002-2012. HCV genotypes were
      determined in 2002-2005 with INNO-LiPA HCV II test (Innogenetics, Gent, Belgium)
      and since 2006 with LINEAR ARRAY assay (Roche, Mannheim, Germany), after
      isolation and amplification of the material with COBAS AMPLICOR v 2.0 (Roche,
      Mannheim, Germany). RESULTS: The most frequent HCV genotype among inmates was
      genotype 3, which was detected in169 of 281 patients (60.1%). Most frequent
      genotype among hospitalized was genotype 1, which was found in 1127 cases
      (79.6%). Comparing the results of prisoners with a group of patients with HIV/HCV
      co-infection gave similar results. In both groups most frequent was genotype 3
      (respectively 60.1 and 45.5%). However, most prisoners in this study (96%) were
      HIV-negative. CONCLUSIONS: The current study shows that the predominant HCV
      genotype among inmates from prison in Potulice is genotype 3.

PMID- 24910704
TI  - Granulocyte colony stimulating factor adjuvant role on the immunological response
      to hepatitis B vaccine in patients with cirrhosis: a double blind randomized
      placebo controlled trial.
AB  - BACKGROUND: Patients with liver cirrhosis have usually poor antibody response to
      hepatitis B virus (HBV) vaccination. OBJECTIVES: This study aimed to investigate
      the effect of granulocyte colony stimulating factor (G-CSF) on increasing
      antibody titers, after HBV vaccination, in patients with liver cirrhosis waiting
      for transplantation. PATIENTS AND METHODS: From 56 patients with cirrhosis, 28
      patients were allocated to receive double dose HBV vaccine (40 MUgr) plus G-CSF
      and 28 patients were allocated to receive double dose HBV vaccine (40 MUgr) plus
      placebo. Injections were performed on weeks 0, 4 and 8 and the blood samples were
      obtained one month after each vaccination session. RESULTS: There was no
      statistically significant difference between anti-HBV antibody titers in patients
      receiving double dose HBV vaccination plus G-CSF and patients receiving double
      dose HBV vaccination plus placebo, after first, second or third vaccination
      rounds (P > 0.05). Although the adjuvant G-CSF injection did not cause
      significant increased antibody titers in our patients compared to the placebo
      group, the increase in antibody titers following vaccination, happened faster in
      this group, compared to the placebo group. CONCLUSIONS: The present study showed
      that G-CSF is not superior to placebo in production of protective antibody titers
      after HBV vaccination but could result in a more rapid antibody response,
      compared to the placebo.

PMID- 24910705
TI  - Hepatitis B seroprevalence and risk factors in adult population of chaharmahal
      and bakhtiari province in 2013.
AB  - BACKGROUND: Hepatitis B virus is one of the important viral causes of liver
      inflammation with high worldwide prevalence and important hepatic and extra
      hepatic complications. OBJECTIVES: The aim of this study was to investigate the
      prevalence and risk factors of hepatitis B in Chaharmahal and Bakhtiari province,
      Iran. PATIENTS AND METHODS: For this descriptive, analytical, population-based
      study, 3000 participants older than 15 years were enrolled according to the
      clustering method. After obtaining written informed consent and taking required
      blood samples, we gathered data on demographic status and probable transmission
      routes of disease using questionnaire between 2012 and 2013. The data was
      analyzed using SPSS software (descriptive parameters and chi-square). P value
      below 0.05 was considered as statistically significant. RESULTS: The mean age of
      participants was 38.4 +/- 16.3. The seroprevalence rate of hepatitis B was found
      to be 1.3% (95% CI, 0.95%-1.81%). Prevalence of HBeAg among HBsAg positive
      participants was 2.5% (only 1 of 40). Seroprevalence was higher in male group
      (2.5 times higher than women), age group of over 55 years, farmers, and non
      public occupations. Positive seroprevalence was associated with a history of
      renal disease, familial transmission, transfusion, surgery in hospital,
      circumcision, contact with hepatitis B infected individuals, imprisonment,
      intravenous (IV) drug abuse, and smoking (P < 0.05). Nevertheless, the highest
      odds ratio (OR) was obtained for history of renal disease (OR = 7.64: 3.01-18.4),
      followed by imprisonment (OR = 5.4: 1.86 -15.7) and IV drug abuse (OR = 5.68: 1.3
      24.7). CONCLUSIONS: Chaharmahal and Bakhtiari province could be categorized as a
      low endemic region for hepatitis B infection, with a seroprevalence similar to
      that in other provinces of western Iran. Vaccination seems to influence its
      decrease, especially in adolescents and youth. More surveillance and attention to
      risk factors are suggested to identify high-risk groups and to implement
      vaccination.

PMID- 24910706
TI  - Long Noncoding RNAs in Interaction With RNA Binding Proteins in Hepatocellular
      Carcinoma.
AB  - BACKGROUND: Gene expression microarrays' analyses provide a description of long
      noncoding RNAs (lncRNAs) with lack of coding protein function that is often
      important in human cancer. OBJECTIVES: A number of lncRNAs that have been well
      characterized in hepatocellular carcinoma (HCC) have been scheduled in this study
      to discuss for protein-lncRNA interaction. MATERIALS AND METHODS: The identified
      lncRNAs were analyzed by bioinformatics tools, starBase and lncRNA db, to
      anticipate the RNA-binding proteins (RBPs) that tend to interact to HCC-related
      lncRNAs. The most important predicted RBPs in interaction with well-known lncRNAs
      in HCC were briefly discussed. RESULTS: The lncRNAs HOTTIP, H19, HOTAIR, MALAT1,
      antisense Igf2r (AIR), HOXA13, GTL2 (also called MEG3) and uc002mb have been
      reported in association with HCC. Besides, this study predicted that eIF4AIII,
      PTB and FUS were the most involved RBPs in interaction with HCC-related lncRNAs.
      CONCLUSIONS: This information provides an explanation for the previously valuable
      literature on the functions of lncRNAs and suggest for the novel therapeutic
      targeting.

PMID- 24910707
TI  - Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma
      metabolites and lipids in C57BL/6J mice.
AB  - BACKGROUND: Diet therapies including calorie restriction, ketogenic diets, and
      fish-oil supplementation have been used to improve health and to treat a variety
      of neurological and non-neurological diseases. METHODS: We investigated the
      effects of three diets on circulating plasma metabolites (glucose and beta
      hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day
      period in C57BL/6J mice. The diets evaluated included a standard rodent diet
      (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish
      oil (FO). Each diet was administered in either unrestricted (UR) or restricted
      (R) amounts to reduce body weight by 20%. RESULTS: The KD-UR increased body
      weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO
      UR decreased body weight and glucose levels and promoted a normolipidemic
      profile, compared to the SD-UR. When administered in restricted amounts, all
      three diets produced a similar plasma metabolite profile, which included
      decreased glucose levels and a normolipidemic profile. Linear regression analysis
      showed that circulating glucose most strongly predicted body weight and
      triglyceride levels, whereas calorie intake moderately predicted glucose levels
      and strongly predicted ketone body levels. CONCLUSIONS: These results suggest
      that biomarkers of health can be improved when diets are consumed in restricted
      amounts, regardless of macronutrient composition.

PMID- 24910710
TI  - Responses to climate and economic risks and opportunities across national and
      ecological boundaries: changing household strategies on the Mongolian plateau.
AB  - Climate changes on the Mongolian Plateau are creating new challenges for the
      households and communities of the region. Much of the existing research on
      household choices in response to climate variability and change focuses on
      environmental risks and stresses. In contrast, our analysis highlights the
      importance of taking into account environmental and economic opportunities in
      explaining household adaptation choices. We surveyed over 750 households arrayed
      along an ecological gradient and matched across the national border in Mongolia
      and the Inner Mongolia Autonomous Region, China, asking what changes in
      livelihoods strategies households made over the last ten years, and analyzed
      these choices in two broad categories of options: diversification and livestock
      management. We combined these data with remotely sensed information about
      vegetation growth and self-reported exposure to price fluctuations. Our
      statistical results showed that households experiencing lower ecological and
      economic variability, higher average levels of vegetation growth, and with
      greater levels of material wealth, were often those that undertook more actions
      to improve their conditions in the face of variability. The findings have
      implications both for how interventions aimed at supporting ongoing choices might
      be targeted and for theory construction related to social adaptation.

PMID- 24910708
TI  - Antiglioma oncolytic virotherapy: unattainable goal or a success story in the
      making?
AB  - Initial observations from as early as the mid-1800s suggested that patients
      suffering from hematological malignancies would transiently go into remission
      upon naturally contracting viral infections laid the foundation for the oncolytic
      virotherapy research field. Since then, research focusing on anticancer oncolytic
      virotherapy has rapidly evolved. Today, oncolytic viral vectors have been
      engineered to stimulate and manipulate the host immune system, selectively
      targeting tumor tissues while sparing non-neoplastic cells. Glioblastoma
      multiforme, the most common adult primary brain tumor, has a disasterous history.
      It is one of the most deadly cancers known to humankind. Over the last century
      our understanding of this disease has grown exponentially. However, the median
      survival of patients suffering from this disease has only been extended by a few
      months. Even with the best, most aggressive modern therapeutic approaches
      available, malignant gliomas are still virtually 100% fatal. Motivated by the
      desperate need to find effective treatment strategies, more investments have been
      applied to oncolytic virotherapy preclinical and clinical studies. In this review
      we will discuss the antiglioma oncolytic virotherapy research field. We will
      survey its history and the principles laid down to serve as basis for preclinical
      works. We will also debate the variety of viral vectors used, their clinical
      applications, the lessons learned from clinical trials and possible future
      directions.

PMID- 24910711
TI  - Modeling Variability in Individual Development: Differences of degree or kind?
AB  - The proper use of statistical models for analyzing individual change over time is
      critical for the progress of developmental science. Latent curve models,
      hierarchical linear growth models, group-based trajectory models, and growth
      mixture models constitute increasingly important tools for longitudinal data
      analysis. To facilitate their understanding and use, this paper clarifies
      similarities and differences between these models, with particular attention to
      the assumptions they make about individual development. An example shows how the
      results and interpretation vary across model types. Discussion centers on
      reviewing the strengths and limitations of each approach for developmental
      research.

PMID- 24910709
TI  - Countermeasure development for Rift Valley fever: deletion, modification or
      targeting of major virulence factor NSs.
AB  - Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized by a
      high rate of abortion in ruminants, and febrile illness, hemorrhagic fever,
      retinitis and encephalitis in humans. RVF is caused by the RVF virus (RVFV),
      belonging to the genus Phlebovirus of the family Bunyaviridae. RVFV encodes a
      major virulence factor, NSs, which is dispensable for viral replication, yet
      required for evasion of host innate immune responses. RVFV NSs inhibits host gene
      upregulation at the transcriptional level, while promoting viral translation in
      the cytoplasm. In this article, we summarize the virology and pathology of RVF,
      and countermeasure development for RVF, with emphasis on NSs function and
      applications.

PMID- 24910712
TI  - Virus-templated Au and Au/Pt Core/shell Nanowires and Their Electrocatalytic
      Activitives for Fuel Cell Applications.
AB  - A facile synthetic route was developed to make Au nanowires (NWs) from surfactant
      mediated bio-mineralization of a genetically engineered M13 phage with specific
      Au binding peptides. From the selective interaction between Au binding M13 phage
      and Au ions in aqueous solution, Au NWs with uniform diameter were synthesized at
      room temperature with yields greater than 98 % without the need for size
      selection. The diameters of Au NWs were controlled from 10 nm to 50 nm. The Au
      NWs were found to be active for electrocatalytic oxidation of CO molecules for
      all sizes, where the activity was highly dependent on the surface facets of Au
      NWs. This low-temperature high yield method of preparing Au NWs was further
      extended to the synthesis of Au/Pt core/shell NWs with controlled coverage of Pt
      shell layers. Electro-catalytic studies of ethanol oxidation with different Pt
      loading showed enhanced activity relative to a commercial supported Pt catalyst,
      indicative of the dual functionality of Pt for the ethanol oxidation and Au for
      the anti-poisoning component of Pt. These new one-dimensional noble metal NWs
      with controlled compositions could facilitate the design of new alloy materials
      with tunable properties.

PMID- 24910713
TI  - Comparison of enzymatic reactivity of corn stover solids prepared by dilute acid,
      AFEXTM, and ionic liquid pretreatments.
AB  - BACKGROUND: Pretreatment is essential to realize high product yields from
      biological conversion of naturally recalcitrant cellulosic biomass, with
      thermochemical pretreatments often favored for cost and performance. In this
      study, enzymatic digestion of solids from dilute sulfuric acid (DA), ammonia
      fiber expansion (AFEXTM), and ionic liquid (IL) thermochemical pretreatments of
      corn stover were followed over time for the same range of total enzyme protein
      loadings to provide comparative data on glucose and xylose yields of monomers and
      oligomers from the pretreated solids. The composition of pretreated solids and
      enzyme adsorption on each substrate were also measured to determine. The extent
      glucose release could be related to these features. RESULTS: Corn stover solids
      from pretreatment by DA, AFEX, and IL were enzymatically digested over a range of
      low to moderate loadings of commercial cellulase, xylanase, and pectinase enzyme
      mixtures, the proportions of which had been previously optimized for each
      pretreatment. Avicel(r) cellulose, regenerated amorphous cellulose (RAC), and
      beechwood xylan were also subjected to enzymatic hydrolysis as controls. Yields
      of glucose and xylose and their oligomers were followed for times up to 120
      hours, and enzyme adsorption was measured. IL pretreated corn stover displayed
      the highest initial glucose yields at all enzyme loadings and the highest final
      yield for a low enzyme loading of 3 mg protein/g glucan in the raw material.
      However, increasing the enzyme loading to 12 mg/g glucan or more resulted in DA
      pretreated corn stover attaining the highest longer-term glucose yields.
      Hydrolyzate from AFEX pretreated corn stover had the highest proportion of
      xylooligomers, while IL produced the most glucooligomers. However, the amounts of
      both oligomers dropped with increasing enzyme loadings and hydrolysis times. IL
      pretreated corn stover had the highest enzyme adsorption capacity. CONCLUSIONS:
      Initial hydrolysis yields were highest for substrates with greater lignin
      removal, a greater degree of change in cellulose crystallinity, and high enzyme
      accessibility. Final glucose yields could not be clearly related to
      concentrations of xylooligomers released from xylan during hydrolysis. Overall,
      none of these factors could completely account for differences in enzymatic
      digestion performance of solids produced by AFEX, DA, and IL pretreatments.

PMID- 24910714
TI  - Fractal correlation property of heart rate variability in response to the
      postural change maneuver in healthy women.
AB  - BACKGROUND: We evaluated the effects of the PCM on the fractal analysis of the
      HRV in healthy women. METHOD: We evaluated healthy women between 18 and 30 years
      old. HRV was analyzed in the time (SDNN, RMSSD, NN50 and pNN50) and frequency
      (LF, HF and LF/HF ratio) domains as well as short and long-term fractal exponents
      (alpha-1 and alpha-2) of the detrended fluctuation analysis (DFA). HRV was
      recorded at rest for ten minutes at seated rest and then the women quickly stood
      up from a seated position in up to three seconds and remained standing for 15
      minutes. HRV was recorded at the following time: rest, 0-5 min, 5-10 min and 10
      15 min during standing. RESULTS: We observed decrease (p < 0.05) in the time
      domain indices of HRV between seated and 10-15 minutes after the volunteer stood
      up. The LF (ms(2)) and HF (ms(2)) indices were also reduced (p < 0.05) at 10-15
      minutes after the volunteer stood up compared to seated while the LF (nu) was
      increased at 5-10 min and 10-15 min (p < 0.05). The short-term alpha-1 exponent
      was increased (p < 0.05) at all moments investigated compared to seated. Increase
      in the properties of short-term fractal correlations of heart rate dynamics
      accompanied by a decrease in the parasympathetic modulation and global HRV was
      observed in response to the postural change maneuver. CONCLUSION: We suggest that
      fractal analysis of HRV is more sensitive than frequency and time-domain analysis
      of HRV during the postural change maneuver.

PMID- 24910715
TI  - Analysis of the role of the Cronobacter sakazakii ProP homologues in
      osmotolerance.
AB  - Bacteria respond to elevated osmolality by the accumulation of a range of low
      molecular weight molecules, known as compatible solutes (owing to their
      compatibility with the cells' normal physiology at high internal concentrations).
      The neonatal pathogen Cronobacter sakazakii is uniquely osmotolerant, surviving
      in powdered infant formula (PIF) which typically has a water activity (aw) of 0.2
      - inhospitable to most micro-organisms. Mortality rates of up to 80% in infected
      infants have been recorded making C. sakazakii a serious cause for concern. In
      silico analysis of the C. sakazakii BAA-894 genome revealed seven copies of the
      osmolyte uptake system ProP. Herein, we test the physiological role of each of
      these homologues following heterologous expression against an osmosensitive
      Escherichia coli host. 

PMID- 24910716
TI  - QSAR DataBank - an approach for the digital organization and archiving of QSAR
      model information.
AB  - BACKGROUND: Research efforts in the field of descriptive and predictive
      Quantitative Structure-Activity Relationships or Quantitative Structure-Property
      Relationships produce around one thousand scientific publications annually. All
      the materials and results are mainly communicated using printed media. The
      printed media in its present form have obvious limitations when they come to
      effectively representing mathematical models, including complex and non-linear,
      and large bodies of associated numerical chemical data. It is not supportive of
      secondary information extraction or reuse efforts while in silico studies poses
      additional requirements for accessibility, transparency and reproducibility of
      the research. This gap can and should be bridged by introducing domain-specific
      digital data exchange standards and tools. The current publication presents a
      formal specification of the quantitative structure-activity relationship data
      organization and archival format called the QSAR DataBank (QsarDB for shorter, or
      QDB for shortest). RESULTS: The article describes QsarDB data schema, which
      formalizes QSAR concepts (objects and relationships between them) and QsarDB data
      format, which formalizes their presentation for computer systems. The utility and
      benefits of QsarDB have been thoroughly tested by solving everyday QSAR and
      predictive modeling problems, with examples in the field of predictive
      toxicology, and can be applied for a wide variety of other endpoints. The work is
      accompanied with open source reference implementation and tools. CONCLUSIONS: The
      proposed open data, open source, and open standards design is open to public and
      proprietary extensions on many levels. Selected use cases exemplify the benefits
      of the proposed QsarDB data format. General ideas for future development are
      discussed.

PMID- 24910717
TI  - Future projections of seasonal patterns in temperature-related deaths for
      Manhattan.
AB  - Global average temperatures have been rising for the past half-century, and the
      warming trend has accelerated in recent decades1. Further warming is expected
      over the next few decades, with significant regional variations. These warming
      trends will likely result in more frequent, intense and persistent periods of hot
      temperatures in summer, and generally higher temperatures in winter. Daily death
      counts in cities increase markedly when temperatures reach levels that are very
      high relative to what is normal in a given location2-4. Relatively cold
      temperatures also appear to carry risk2,4. Rising temperatures may result in more
      heat-related mortality but may also reduce cold-related mortality, and the net
      impact on annual mortality remains uncertain. Here we use 16 downscaled global
      climate models and two emissions scenarios to estimate current and future
      seasonal patterns in temperature-related mortality in Manhattan, New York. All 32
      projections yielded warm season increases and cold season decreases in
      temperature-related mortality, with positive net annual temperature-related
      deaths in all cases. Monthly analyses showed that the largest percentage
      increases may occur in May and September. These results suggest that, over a
      range of models and scenarios of future greenhouse gas emissions, increases in
      heat-related mortality could outweigh reductions in cold-related mortality, with
      shifting seasonal patterns.

PMID- 24910718
TI  - Us versus Them in Context: Meta-Analysis as a Tool for Geotemporal Trends in
      Intergroup Relations.
AB  - The increasing availability of studies from many nations offers important
      potential insights into group-based psychology and behavior, conflict, and
      violence. Nonetheless, to date, few cross-national or cultural comparisons of
      study findings have been made, representing a gap in our understanding of the
      historical causes and courses of intergroup conflict in current comparative
      approaches. Meta-analytic methods offer researchers the ability to combine data
      from studies with groups as well as across time. Our review of statistical
      methods available for comparative analyses in intergroup research found strengths
      and limitations for understanding group differences, conflict, and violence, and
      meta-analytic methods address these limitations by exploring potential structural
      level moderators and by identifying how temporal and geographical variations may
      relate directly to group-based variables. Such methods can contribute to our
      understanding of broad structural effects on group-based variables by elucidating
      the mechanisms underlying them.

PMID- 24910719
TI  - Hydraulic Pressure during Fluid Flow Regulates Purinergic Signaling and
      Cytoskeleton Organization of Osteoblasts.
AB  - During physiological activities, osteoblasts experience a variety of mechanical
      forces that stimulate anabolic responses at the cellular level necessary for the
      formation of new bone. Previous studies have primarily investigated the
      osteoblastic response to individual forms of mechanical stimuli. However in this
      study, we evaluated the response of osteoblasts to two simultaneous, but
      independently controlled stimuli; fluid flow-induced shear stress (FSS) and
      static or cyclic hydrostatic pressure (SHP or CHP, respectively). MC3T3-E1
      osteoblasts-like cells were subjected to 12dyn/cm2 FSS along with SHP or CHP of
      varying magnitudes to determine if pressure enhances the anabolic response of
      osteoblasts during FSS. For both SHP and CHP, the magnitude of hydraulic pressure
      that induced the greatest release of ATP during FSS was 15 mmHg. Increasing the
      hydraulic pressure to 50 mmHg or 100 mmHg during FSS attenuated the ATP release
      compared to 15 mmHg during FSS. Decreasing the magnitude of pressure during FSS
      to atmospheric pressure reduced ATP release to that of basal ATP release from
      static cells and inhibited actin reorganization into stress fibers that normally
      occurred during FSS with 15 mmHg of pressure. In contrast, translocation of
      nuclear factor kappa B (NFkappaB) to the nucleus was independent of the magnitude
      of hydraulic pressure and was found to be mediated through the activation of
      phospholipase-C (PLC), but not src kinase. In conclusion, hydraulic pressure
      during FSS was found to regulate purinergic signaling and actin cytoskeleton
      reorganization in the osteoblasts in a biphasic manner, while FSS alone appeared
      to stimulate NFkappaB translocation. Understanding the effects of hydraulic
      pressure on the anabolic responses of osteoblasts during FSS may provide much
      needed insights into the physiologic effects of coupled mechanical stimuli on
      osteogenesis.

PMID- 24910720
TI  - Accounting for the Hierarchical Structure in Veterans Health Administration Data:
      Differences in Healthcare Utilization between Men and Women Veterans.
AB  - Women currently constitute 15% of active United States of America military
      service personnel, and this proportion is expected to double in the next 5 years.
      Previous research has shown that healthcare utilization and costs differ in women
      US Veterans Health Administration (VA) patients compared to men. However, none
      have accounted for the potential effects of clustering on their estimates of
      healthcare utilization. US Women Veterans are more likely to serve in specific
      military branches (e.g. Army), components (e.g. National Guard), and ranks (e.g.
      officer) than men. These factors may confer different risk and protection that
      can affect subsequent healthcare needs. Our study investigates the effects of
      accounting for the hierarchical structure of data on estimates of the association
      between gender and VA healthcare utilization. The sample consisted of data on
      406,406 Veterans obtained from VA's Operation Enduring Freedom/Operation Iraqi
      Freedom roster provided by Defense Manpower Data Center - Contingency Tracking
      System Deployment File. We compared three statistical models, ordinary, fixed and
      random effects hierarchical logistic regression, in order to assess the
      association of gender with healthcare utilization, controlling for branch of
      service, component, rank, age, race, and marital status. Gender was associated
      with utilization in ordinary logistic and, but not in fixed effects hierarchical
      logistic or random effects hierarchical logistic regression models. This point
      out that incomplete inference could be drawn by ignoring the military structure
      that may influence combat exposure and subsequent healthcare needs. Researchers
      should consider modeling VA data using methods that account for the potential
      clustering effect of hierarchy.

PMID- 24910722
TI  - Texture Descriptors to distinguish Radiation Necrosis from Recurrent Brain Tumors
      on multi-parametric MRI.
AB  - Differentiating radiation necrosis (a radiation induced treatment effect) from
      recurrent brain tumors (rBT) is currently one of the most clinically challenging
      problems in care and management of brain tumor (BT) patients. Both radiation
      necrosis (RN), and rBT exhibit similar morphological appearance on standard MRI
      making non-invasive diagnosis extremely challenging for clinicians, with surgical
      intervention being the only course for obtaining definitive "ground truth".
      Recent studies have reported that the underlying biological pathways defining RN
      and rBT are fundamentally different. This strongly suggests that there might be
      phenotypic differences and hence cues on multi-parametric MRI, that can
      distinguish between the two pathologies. One challenge is that these differences,
      if they exist, might be too subtle to distinguish by the human observer. In this
      work, we explore the utility of computer extracted texture descriptors on multi
      parametric MRI (MP-MRI) to provide alternate representations of MRI that may be
      capable of accentuating subtle micro-architectural differences between RN and rBT
      for primary and metastatic (MET) BT patients. We further explore the utility of
      texture descriptors in identifying the MRI protocol (from amongst T1-w, T2-w and
      FLAIR) that best distinguishes RN and rBT across two independent cohorts of
      primary and MET patients. A set of 119 texture descriptors (co-occurrence matrix
      homogeneity, neighboring gray-level dependence matrix, multi-scale Gaussian
      derivatives, Law features, and histogram of gradient orientations (HoG)) for
      modeling different macro and micro-scale morphologic changes within the treated
      lesion area for each MRI protocol were extracted. Principal component analysis
      based variable importance projection (PCA-VIP), a feature selection method
      previously developed in our group, was employed to identify the importance of
      every texture descriptor in distinguishing RN and rBT on MP-MRI. PCA-VIP employs
      regression analysis to provide an importance score to each feature based on their
      ability to distinguish the two classes (RN/rBT). The top performing features
      identified via PCA-VIP were employed within a random-forest classifier to
      differentiate RN from rBT across two cohorts of 20 primary and 22 MET patients.
      Our results revealed that, (a) HoG features at different orientations were the
      most important image features for both cohorts, suggesting inherent orientation
      differences between RN, and rBT, (b) inverse difference moment (capturing local
      intensity homogeneity), and Laws features (capturing local edges and gradients)
      were identified as important for both cohorts, and (c) Gd-C T1-w MRI was
      identified, across the two cohorts, as the best MRI protocol in distinguishing
      RN/rBT.

PMID- 24910723
TI  - Hypothermia, shivering, and dexmedetomidine.

PMID- 24910724
TI  - Awareness and recall during general anesthesia.
AB  - Anesthesia awareness is defined as both consciousness and recall of surgical
      events. New research has been conducted out to test this phenomenon. However,
      testing methods have not proven reliable, including those using devices based on
      electroencephalographic techniques to detect and prevent intraoperative
      awareness. The limitations of a standard intraoperative brain monitor reflect our
      insufficient understanding of consciousness. Moreover, patients who experience an
      intraoperative awareness can develop serious post-traumatic stress disorders that
      should not be overlooked. In this review, we introduce the incidence of
      intraoperative awareness during general anesthesia and discuss the mechanisms of
      consciousness, as well as risk factors, various monitoring methods, outcome and
      prevention of intraoperative awareness. 

PMID- 24910725
TI  - The simultaneous application of positive-end expiratory pressure with the
      Trendelenburg position minimizes respiratory fluctuations in internal jugular
      vein size.
AB  - BACKGROUND: The respiratory cycle alters the size of the right internal jugular
      vein (RIJV). We assessed the changes in RIJV size during the respiratory cycle in
      patients under positive pressure ventilation. Moreover, we examined the effects
      of positive-end expiratory pressure (PEEP) and the Trendelenburg position on
      respiratory fluctuations. METHODS: A prospective study of 24 patients undergoing
      general endotracheal anesthesia was performed. Images of the RIJV were obtained
      in the supine position with no PEEP (baseline, S0) and after applying three
      different maneuvers in random order: (1) a PEEP of 10 cmH2O (S10), (2) a 10
      degrees  Trendelenburg tilt position (T0), and (3) a 10 degrees  Trendelenburg
      tilt position combined with a PEEP of 10 cmH2O (T10). Using the images when the
      area was smallest and largest, cross-sectional area (CSA), anteroposterior
      diameter, and transverse diameter were measured. RESULTS: All maneuvers minimized
      the fluctuation in RIJV size (all P = 0.0004). During the respiratory cycle, the
      smallest CSA compared to the largest CSA at S0, S10, T0, and T10 decreased by
      28.3 8.5, 8.0, and 4.4%, respectively. Furthermore, compared to S0, a 10 degrees 
      Trendelenburg tilt position with a PEEP of 10 cmH2O significantly increased the
      CSA in the largest areas by 83.8% and in the smallest areas by 169.4%.
      CONCLUSIONS: A 10 degrees  Trendelenburg tilt position combined with a PEEP of 10
      cmH2O not only increases the size of the RIJV but also reduces fluctuation by the
      respiratory cycle.

PMID- 24910721
TI  - 2. Hypoglycemia Detection.

PMID- 24910726
TI  - Comparison of the efficacy of a forced-air warming system and circulating-water
      mattress on core temperature and post-anesthesia shivering in elderly patients
      undergoing total knee arthroplasty under spinal anesthesia.
AB  - BACKGROUND: In the present study, we compared changes in body temperature and the
      occurrence of shivering in elderly patients undergoing total knee arthroplasty
      under spinal anesthesia during warming with either a forced-air warming system or
      a circulating-water mattress. METHODS: Forty-six patients were randomly assigned
      to either the forced-air warming system (N = 23) or circulating-water mattress (N
      = 23) group. Core temperature was recorded using measurements at the tympanic
      membrane and rectum. In addition, the incidence and intensity of post-anesthesia
      shivering and verbal analogue score for thermal comfort were simultaneously
      assessed. RESULTS: Core temperature outcomes did not differ between the groups.
      The incidence (13.0 vs 43.5%, P < 0.05) and intensity (20/2/1/0/0 vs 13/5/3/2/0,
      P < 0.05) of post-anesthesia shivering was significantly lower in the forced-air
      system group than in the circulating-water mattress group. CONCLUSIONS: The
      circulating-water mattress was as effective as the forced-air warming system for
      maintaining body temperature. However, the forced-air warming system was superior
      to the circulating-water mattress in reducing the incidence of post-anesthesia
      shivering.

PMID- 24910727
TI  - The influence of different mechanical ventilator settings of peak inspiratory
      pressure on stroke volume variation in pediatric cardiac surgery patients.
AB  - BACKGROUND: The usefulness of dynamic parameters derived by heart-lung
      interaction for fluid responsiveness in pediatric patients has been revealed.
      However, the effects of peak inspiratory pressure (PIP) that could affect the
      absolute values and the accuracy in pediatric patients have not been well
      established. METHODS: Participants were 30 pediatric patients who underwent
      ventricular septal defect repair. After completion of surgical procedure and
      sternum closure, mean arterial blood pressure, heart rate, central venous
      pressure, cardiac output, cardiac index and stroke volume variation (SVV) were
      measured at PIP 10 cmH2O (PIP10), at PIP 15 cmH2O (PIP15), at PIP 20 cmH2O
      (PIP20) and at PIP 25 cmH2O (PIP25). RESULTS: SVV at PIP15 was larger than that
      at PIP10 (13.7 +/- 2.9% at PIP10 vs 14.7 +/- 2.5% at PIP15, P < 0.001) and SVV at
      PIP20 was larger than that at PIP10 and PIP15 (13.7 +/- 2.9% at PIP10 vs 15.4 +/-
      2.5% at PIP20, P < 0.001; 14.7 +/- 2.5% at PIP15 vs 15.4 +/- 2.5% at PIP20, P <
      0.001) and SVV at PIP25 was larger than that at PIP10 and PIP15 and PIP20 (13.7
      +/- 2.9% at PIP10 vs 17.4 +/- 2.4% at PIP25, P < 0.001; 14.7 +/- 2.5% at PIP15 vs
      17.4 +/- 2.4% at PIP25, P < 0.001; 15.4 +/- 2.5% at PIP20 vs 17.4 +/- 2.4% at
      PIP25, P < 0.001). CONCLUSIONS: SVV is affected by different levels of PIP in
      same patient and under same volume status. This finding must be taken into
      consideration when SVV is used to predict fluid responsiveness in mechanically
      ventilated pediatric patients.

PMID- 24910728
TI  - Effects of general and spinal anesthetic techniques on endothelial adhesion
      molecules in cesarean section.
AB  - BACKGROUND: The aim of this study was to investigate the effects of anesthetic
      techniques used during general anesthesia (GA) and spinal anesthesia (SA) on
      endothelial adhesion molecules in the fetal circulation of healthy parturients
      undergoing elective cesarean section. METHODS: Patients were randomly assigned to
      either the general anesthesia (n = 20) or spinal anesthesia (n = 20) group.
      Maternal and cord blood neopterin, sE-selectin, and sL-selectin levels were
      measured in both groups. RESULTS: Cord blood neopterin concentrations in the SA
      group were not different from those in the GA group, but maternal neopterin
      levels in the SA group were different from those in the GA group. Maternal blood
      levels of sE-selectin and sL-selectin were not different between the two groups.
      Similarly, the cord blood levels of sE-selectin and sL-selectin were not
      different between the two groups. We found an increased inflammatory process in
      the fetal circulation depending on the anesthetic method used. CONCLUSIONS: These
      results indicate the effects of general and spinal anesthetic techniques on serum
      sL-selectin, sE-selectin, and neopterin levels in neonates and parturients
      undergoing elective cesarean section. sE-selectin and neopterin concentrations
      and leukocyte counts were higher in the fetal circulation than in the maternal
      circulation during both GA and SA.

PMID- 24910729
TI  - Comparison of two dosing schedules of intravenous dexmedetomidine in elderly
      patients during spinal anesthesia.
AB  - BACKGROUND: As the number of elder patients grows, spinal anesthesia for such
      patients are increasing significantly. Any effort is needed to use the least
      anesthetic drug for maintaining the anesthesia while avoiding hazards of cardio
      pulmonary complications. METHODS: American Society of Anesthesiologists physical
      status classification I and II, Forty five elderly patients (>= 60 years) who
      received transurethral resection of the prostate or transurethral resection of
      the bladder tumor were allocated randomly into three treatment groups. The DMT
      0.5 group was designed as with dexmedetomidine 0.5 ug/kg while the DMT 1.0 group
      has a 1 ug/kg intravenous injection over 10 min before anesthetic induction. The
      Control group was designed to get a normal saline. Each group was compared
      regarding the maximum sensory block level, extension of anesthesia, degree of
      motor block, level of sedation, VAS score and complications. RESULTS: There were
      no significant differences among the 3 treatment groups regarding the maximum
      level of sensory block and motor block. However, the duration of sensory block
      was significantly longer in DMT 1.0 group than in the control group (P = 0.045).
      Both DMT 1.0 group (median = 3, range = 2-6) and DMT 0.5 group (median = 3, range
      = 1-6) showed a mean value of 3-4 Ramsay sedation score, which resulted in more
      excessive sedation and significantly greater incidence of bradycardia compared to
      the control group. No complications such as hypotension, nausea, tremor, and
      hypoxia were found during this investigation. CONCLUSIONS: In elder patients, the
      DMT 1.0 group is effective in duration of sensory block and is superior in the
      aspect of prolonged duration of sensory block compared to the DMT 0.5 group.

PMID- 24910730
TI  - Correction of target-controlled infusion following wrong selection of emulsion
      concentrations of propofol.
AB  - BACKGROUND: We investigated the correction methods following wrong-settings of
      emulsion concentrations of propofol as a countermeasure against erroneous target
      controlled infusions (TCI). METHODS: TCIs were started with targeting 4.0 ug/ml
      of effect-site concentration (Ceff) of propofol, and the emulsion concentrations
      were selected for 2.0% instead of 1.0% (FALSE1-2, n = 24), or 1.0% instead of
      2.0% (FALSE2-1, n = 24). These wrong TCIs were corrected at 3 min after infusion
      start. During FALSE1-2, the deficit was filled up while injecting after
      equilibrium (n = 12), or while overriding (n = 12). During FALSE2-1, the overdose
      was evacuated while targeting Ceff (n = 12) or targeting plasma concentration
      (Cp) (n = 12). The gravimetrical measurements of TCI reproduced the Cp and Ceff
      using simulations. The reproduced Ceff at 3 min (Ceff-3min) and the time to be
      normalized within +/- 5% of target Ceff (T+/-5%), were compared between the
      correction methods. RESULTS: During the wrong TCI, Ceff-3min was 1.98 +/- 0.01
      ug/ml in FALSE1-2, and 7.99 +/- 0.05 ug/ml in FALSE2-1. In FALSE1-2, T+/-5% was
      significantly shorter when corrected while overriding (3.9 +/- 0.25 min), than
      corrected after equilibrium (6.9 +/- 0.05 min) (P < 0.001). In FALSE2-1, T+/-5%
      was significantly shorter during targeting Cp (3.6 +/- 0.04 min) than targeting
      Ceff (6.7 +/- 0.15 min) (P < 0.001). CONCLUSIONS: The correction methods, based
      on the pharmacokinetic and pharmacodynamic characteristics, could effectively and
      rapidly normalize the wrong TCI following erroneously selections of the emulsion
      concentration of propofol.

PMID- 24910731
TI  - Cardiopulmonary resuscitation with assisted extracorporeal life support during
      cardiac arrest caused by drug-eluting stent thrombosis: a case report.
AB  - Discontinuation of dual antiplatelet therapy within 12 months after drug-eluting
      stent (DES) implantation increases the possibility of stent thrombosis. We now
      report the case of a 66-year-old man who suffered a cardiac arrest due to stent
      thrombosis after an elective laparoscopic anterior resection. Ten month ago, he
      underwent DES implantation and then had been taking dual antiplatelet therapy.
      Nine days prior to the surgery, he discontinued dual antiplatelet therapy. Forty
      minutes after intensive care unit admission, cardiac arrest occurred. However,
      his cardiac rhythm did not restore in spite of resuscitation, so immediately veno
      arterial extracorporeal membrane oxygenation (ECMO) was implanted. Four days
      after the surgery, he was weaned from ECMO support, recovered completely, with no
      cardiopulmonary or neurological sequelae. 

PMID- 24910732
TI  - Cardiovascular collapse due to right heart failure following ethanol
      sclerotherapy: a case report.
AB  - Ethanol sclerotherapy for the treatment of low-flow vascular malformations can
      cause catastrophic cardiopulmonary complications, including pulmonary embolism
      and pulmonary hypertension, that can result in right heart failure and fatal
      arrhythmias, leading to death. We here report a case of abrupt cardiovascular
      collapse that developed immediately following ethanol sclerotherapy in 31-year
      old female patient who had a large arteriovenous malformation in her leg.
      Anesthesiologists should be aware of the fatal cardiopulmonary complications that
      are associated with ethanol sclerotherapy and consider the use of invasive
      hemodynamic monitoring, such as pulmonary artery pressure monitoring, when large
      doses of ethanol are required. 

PMID- 24910733
TI  - Anesthetic experience using extracorporeal membrane oxygenation for cesarean
      section in the patient with peripartum cardiomyopathy: a case report.
AB  - Peripartum cardiomyopathy is a rare form of cardiomyopathy that is associated
      with significant mortality. It can cause a cardiac arrest during cesarean section
      even though the patient does not have any previous symptom and sign. The most
      important thing of anesthesia in this patient is an optimization of hemodynamic
      and respiratory status. We report the successful general anesthesia using of
      extracorporeal membrane oxygenation for cesarean section in a 34-year-old woman
      with fulminant peripartum cardiomyopathy. 

PMID- 24910734
TI  - Rapid progressive atypical atraumatic osteonecrosis of humeral head: a case
      report.
AB  - Osteonecrosis of the humeral head is an uncommon and slow progressive condition.
      This condition is difficult to be recognized because its initial symptoms are
      nonspecific. Simple radiography is the standard tool to stage disease
      progression. However, plain radiographic findings of osteonecrosis are nearly
      normal in the initial stage. We report a case of 74 years old female patient who
      have suffered from painful limitation of the shoulder joint. She had no trauma
      history and no specific predisposing factors for osteonecrosis of the humeral
      head. To confirm, follow up radiography and shoulder magnetic resonance imaging
      were performed. 

PMID- 24910735
TI  - Intraarterial mechanical thrombectomy for the treatment of postoperative cerebral
      infarction: a case report.
AB  - Perioperative ischemic stroke is an uncommon event associated with significant
      morbidity and mortality. The complexity of the surgical procedure and surgery
      induced hypercoagulable status also influence the incidence of stroke. The
      management of stroke involves a decision regarding the quickest suitable
      revascularization method. Endovascular mechanical thrombectomy, such as intra
      arterial mechanical thrombectomy (IAMT), can restore vascular patency of the
      vessels, providing an alternative or synergistic method to restore blood flow.
      Although, there are no recommended treatment guidelines, IAMT is eligible to be a
      treatment of choice for perioperative ischemic stroke. We experienced a case of a
      patient who demonstrated hemiplegia and aphasia, the early symptom of acute
      ischemic stroke, in the post-anesthesia care unit and performed IAMT
      successfully. Thus we report the case with a review of the relevant literature. 

PMID- 24910736
TI  - Nasogastric tube placement using a semi-rigid esophageal stethoscope in an
      intubated surgical patient.

PMID- 24910737
TI  - Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a
      Meta-analysis.
AB  - OBJECTIVE: To systematically evaluate therapeutic success of the ketogenic diet
      (KD) as a treatment option for epilepsy. METHODS: Using MEDLINE and Google
      Scholar search, we searched for studies investigating the therapeutic success of
      ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic
      diet as a treatment option for epilepsy and its 95% CIs using generic inverse
      variance method. FINDINGS: A total of 38 studies met the inclusion criteria. In
      retrospective studies, the weighted success rate of the patients who take the KD
      as a treatment option for epilepsy was 58.4% (95% confidence interval
      (95%CI)=48.7% - 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% - 50.3%) at 6
      months (n=492), and 30.1% (95%CI =24.3% - 37.2%) at 12 months (n=387); in
      prospective studies, weighted success rate was 53.9% (95%CI 45.5% - 63.8%) at 3
      months (n=474); 53.2% (95%CI =44.0% - 64.2%) at 6 months (n=321), and 55.0%
      (95%CI =45.9% - 65.9%) at 12 months (n=347). CONCLUSION: This meta-analysis
      provides formal statistical support for the efficacy of the ketogenic diet in the
      treatment of epileptic patients.

PMID- 24910739
TI  - Clinical profile of snake bite in children in rural India.
AB  - OBJECTIVE: A high incidence of snake bite envenomation has been reported from
      rural India. Due to inadequate epidemiological data, the incidence is
      underestimated. This study analyses the pattern of snake bite and their
      management in children in rural areas of Maharashtra, India. To determine the
      age, mode of presentation, seasonal variation, clinical profile and outcome of
      patients with snake bite less than 15 years of age. METHODS: This study is a
      retrospective, descriptive study including 162 patients, who presented with
      history of snake bite. Clinical data about age, sex, clinical manifestations,
      complications and outcome were obtained from case records and were analyzed.
      FINDINGS: Out of the 162 patients 98 (60.49%) were males. The bites were
      vasculotoxic in 147 (90.74%) and neuroparalytic in 15 (9.25%) patients. Mainly
      bites occurred from July to September with 84 (51.85%) bites. Bites were more
      common in males in age more than 5 years (89%) with bite marks mainly on lower
      limbs in 120 (74.04%) patients. Deaths were reported in patients who reported
      late to the hospital with a mortality rate of 1.85%. CONCLUSION: Snake bite is a
      life threatening emergency. The key to minimizing mortality and severe morbidity
      is aggressive management of the ABC's of resuscitation, and timely and judicious
      administration of adequate dose of anti-venom.

PMID- 24910738
TI  - Obese and overweight children and adolescents: an algorithmic clinical approach.
AB  - Obesity in children and adolescents is a hot issue throughout the world. Numerous
      complications are related to childhood obesity, such as cardiovascular disease,
      diabetes, insulin resistance and psychological problems. Therefore,
      identification and treatment of this problem have an important role in the health
      system. In this clinical approach, we have provided a general overview of the
      assessment and management of obesity in children and adolescents, including
      definitions, history-taking, physical examinations, and laboratory testing for
      general practitioners and pediatricians. Furthermore, conventional therapies
      (physical activity, eating habits and behavioral modification) and non
      conventional treatments (drugs and surgery options) have been discussed. 

PMID- 24910740
TI  - Frequency of shiga toxin-producing genes of Escherichia coli isolated from
      diarrheic stools of Iranian children by PCR.
AB  - OBJECTIVE: Shiga toxin-producing E. coli (STEC) is a pathogenic E. coli that may
      cause hemolytic uremic syndrome (HUS) after diarrheal disease through Shiga
      toxins. Management of the patients with STEC infection is different from that of
      other diarrheal diseases due to increase in frequency of HUS after antibiotic
      administration. Few studies were conducted in Iran and epidemiology of STEC
      remains obscure; this necessitates examination of stools especially in young
      children for this bacterium. METHODS: We determined the frequency of STEC in 947
      E. coli strains isolated from diarrheal stools of children less than 14 years in
      Tehran with conventional culture methods and multiplex-PCR via determining the
      STX1 and STX2 genes, between October 2008 and September 2009. We also evaluated
      the association between stool exam findings and presence of STEC. FINDINGS:
      Twenty seven (2.8%) of E. coli isolates were positive for STX1 or STX2 genes,
      most of which occurred in spring (P<0.05). There was no significant association
      between STEC positivity and stool exam findings. Eighteen out of 27 (66.7%) Shiga
      toxin positive samples were isolated from males and the rest from females. The
      most common STX-positive diarrheal samples showed loose consistency (P<0.017).
      CONCLUSION: Although the low frequency of STEC in our population indicates that
      it is not a major problem in our population, STEC should be regarded as an
      important infection because of its severe consequences. Further studies with
      greater sample size are needed to confirm our results.

PMID- 24910741
TI  - Ceftriaxone-associated nephrolithiasis in children.
AB  - OBJECTIVE: Ceftriaxone is a third-generation cephalosporin which is widely used
      for treatment of infection in children accompanied by complications like urinary
      tract lithiasis and gallbladder psudolithiasis or sludge. The aim of this study
      was to investigate the incidence and predisposing factors that contribute to
      these complications in children. METHODS: This quasi-experimental and before- and
      after-study was conducted in 96 children who were hospitalized for treatment of
      different bacterial infections and received 50-100 mg/kg/day ceftriaxone divided
      into two equal doses intravenously under conditions of adequate hydration.
      Sonographic examinations of urinary tract and gallbladder were carried out before
      and after treatment for that purpose. Patients with positive sonographic findings
      after treatment were followed with serial sonographic examinations. FINDINGS:
      Post-treatment sonography demonstrated nephrolithiasis in 6 (6.3%) and
      gallbladder stone in one (1%), all were asymptomatic. Comparison of the groups
      with and without nephrolithiasis demonstrated no significant differences with
      respect to age, body weight, diagnosis, season of hospitalization, dosage of drug
      and the duration of treatment. Nephrolithiasis had a significant relation with
      male gender (P=0.02). CONCLUSION: Our results showed that pediatric patients may
      develop small sized, asymptomatic renal stones during a 2-6 day course of normal
      or moderate dose of ceftriaxone therapy. Close monitoring of ceftriaxone treated
      patients especially on high dose long term therapy for nephrolithiasis and
      gallbladder psudolithiasis or sludge is recommended.

PMID- 24910742
TI  - Protective temporary vesicostomy for upper urinary tract problems in children: a
      five-year experience.
AB  - OBJECTIVE: Temporary vesicostomy is a urinary diversion procedure for patients
      with upper urinary tract (UUT) dilatation, secondary to bladder outlet
      obstruction or dysfunction. The aim of this study was to evaluate our experience
      in children undergoing such diversion, analyzing its efficacy to prevent urinary
      tract infection (UTI), improve or resolve hydronephrosis, stabilize or improve
      kidney function and restore the health of UUT. METHODS: In this retrospective
      study, patients who had vesicostomy by Blocksom technique due to bladder outlet
      obstruction or dysfunction were evaluated in Mofid Children's Hospital (in
      Tehran) from March 2007 to March 2012. The reason for applying this procedure was
      failure in clinical treatment. Data regarding gender, age, diagnosis, time of any
      surgical intervention, associated anomalies, primary/secondary complications and
      mortality were collected using a questionnaire, and evaluated by giving a grade
      that ranged from 0 (worst) to 10 (best) based on Lickert's scale. FINDINGS: From
      a total number of 53 patients, (88.7% male and 11.3% female) with a mean age of
      225 days, 66% had posterior urethral valve and 16 (30%) neurogenic bladder. UTI
      was present in all cases, hydronephrosis in 52 (98.1%), and vesico-ureteral
      reflux only in 45 (84.9%) patients. Valve ablation was performed in 17 cases, and
      clean intermittent catheterization in14 patients which were unsuccessful. We
      performed vesicostomy in all patients. Mortality rate was 7.5%. Vesicostomy was
      closed in 35 patients. Cure rate was 85% in UTI, 82.7% in hydronephrosis, 80% in
      VUR, and 86.5% in kidney function. CONCLUSION: Vesicostomy is a simple procedure
      that protects upper urinary tract, decreases hydronephrosis, and improves kidney
      function. The procedure is well tolerated and reversible, with less complication
      and should be considered in children in whom conservative and medical treatment
      has failed.

PMID- 24910743
TI  - Clinical trial of vigabatrin as adjunctive therapy in children with refractory
      epilepsy.
AB  - OBJECTIVE: Approximately one-third of all children with epilepsy do not achieve
      complete seizure improvement. This study evaluated the efficacy of Vigabatrin in
      children with intractable epilepsy. METHODS: From November 2011 to October 2012,
      73 children with refractory epilepsy (failure of seizure control with the use of
      two or more anticonvulsant drugs) who were referred to the Children's Medical
      Center and Mofid Children's Hospital were included in the study. The patients
      were treated with Vigabatrin in addition to their previous medication, and
      followed-up after three to four weeks to determine the daily frequency, severity,
      and duration of seizures in addition to any reported side effects. FINDINGS: Of
      the 67 children, 41 (61.2%) were males and 26 (38.8%) females, their age ranging
      from three months to 13 years with an average of 3.1 [standard deviation (SD),
      2.6] years. The mean daily frequency of seizures at baseline was 6.61 (SD, 5.9)
      seizures per day. Vigabatrin reduced the seizure frequency <=2.9 (SD, 5.2) (56%
      decline) and 3.0 (SD, 5.3) (54.5% decline) per day after three and six months of
      treatment, respectively. A significant difference was observed between seizure
      frequencies at three (P<0.001) and six months (P<0.001) after Vigabatrin
      initiation compared with the baseline. Somnolence [3 (4.5%)], horse laugh [1
      (1.5%)], urinary stones [1 (1.5%)], increased appetite [1 (1.5%)], and abnormal
      electroretinographic pattern [3 (4.5%)] were the most common side effects in our
      patients. CONCLUSION: This study confirms the short-term efficacy and safety of
      Vigabatrin in children with refractory epilepsies.

PMID- 24910744
TI  - Resistin in cord blood of small for gestation age and appropriate for gestation
      age term neonates.
AB  - OBJECTIVE: Placental hormones such as resistin, adiponectin, ghrelin and leptin
      are known to have considerable role in fetal growth and there are some articles
      published in this area recently. Nevertheless there is a shortage of data showing
      association between resistin level and fetal growth; that was why we decided to
      conduct a study to evaluate this association. METHODS: This study was approved by
      ethic committee of pediatric health research center and research vice chancellor
      of Tabriz University of Medical Sciences. In this case-control study we measured
      the insulin, glucose and resistin in the cord blood of neonates with gestational
      age of 37 weeks or more in Al Zahra tertiary hospital from March 2011 to March
      2012. Thirty-nine appropriate for gestation age (AGA) neonates and 41 small for
      gestation age (SGA) neonates were studied. FINDINGS: The umbilical cord blood
      resistin level was not found to have significant correlation with the type of
      delivery [normal vaginal delivery (NVD) or cesarean-section (C-S)], neonate's
      gender, maternal age or body mass index (BMI). There was no significant
      difference in the levels of Insulin and glucose between AGA and SGA groups.
      Resistin level of blood cord in AGA group was 613.76+/-180.10 (range: 132.6
      983.80 ng/ml) and in SGA group it was 1303.47+/-537.07 (range: 800.9-3001 ng/ml)
      (P<0.001). Neonates' weight in AGA group was 3162.82+/-407.92 g and in SGA group
      it was 2425.85+/-32.84 g (P<0.001). CONCLUSION: In this study resistin level had
      reverse correlation with fetal weight in term neonates. The SGA neonates with
      growth insufficiency have higher resistin levels in their cord blood than AGA
      neonates with same gestational age. It is recommended to conduct more studies in
      future with larger population of patients to clarify the resistin role in
      neonatal birth weight.

PMID- 24910745
TI  - Cardiac malformations in fetuses of gestational and pre gestational diabetic
      mothers.
AB  - OBJECTIVE: In this study we aimed to determine the prevalence of cardiac
      malformations in fetuses of Iranian diabetic mothers with pre-gestational and
      gestational diabetes mellitus (GDM) and to find the patterns of different cardiac
      malformations. METHODS: One-hundred and seventy diabetic pregnant women (68
      preGDM and 102 GDM) (mean age: 32.17+/-4.8 years) and 85 healthy controls (mean
      age: 31.35+/-4.55 years) were recruited from September 2008 to July 2012. Fetal
      echocardiography was performed to assess cardiac malformation. In order to study
      major factors that may affect the results, a complete history was obtained.
      FINDINGS: Fetal echocardiography was performed at mean gestational age of 24.7+/
      5.4 and 20.27+/-3.9 weeks in diabetic patients and control group, respectively.
      Fifteen (8.8%) fetuses of diabetic mothers were detected to have cardiac
      malformations compared with 1 (1.17%) fetus in control group (OR: 8.13, 95%CI:
      1.1-62.61, P-value=0.02). Hypertrophic cardiomyopathy noted as the most common
      cardiac malformation occurred in 6 out of 15 (40%) fetuses, and was found
      significantly more common in pre-GDM compared to GDM group (7.4% vs 1%, P-value
      =0.04). Despite the higher incidence of cardiac malformation in pre-GDM compared
      to GDM group, the difference was not significant. Further, no significant
      association was observed between the variables including; parity, diabetic
      regimen, parents' consanguinity, maternal history of hypertension or
      hypothyroidism and occurring cardiac malformations (P-value>0.05). CONCLUSION: In
      this study we detected cardiac malformations in 8.8% of our diabetic referrals.
      The result of the present study shows that screening diabetic mothers for fetal
      cardiac malformations could be beneficial.

PMID- 24910746
TI  - Effects of probiotics on quality of life in children with cystic fibrosis; a
      randomized controlled trial.
AB  - OBJECTIVE: Patients with cystic fibrosis (CF) usually have abnormal intestinal
      microbiota and dysregulated immune mediators due to massive exposure to
      antibiotics. Probiotics as immunomodulatory and anti-inflammatory substances are
      considered to improve both clinical and biochemical intestinal and pulmonary
      function in CF patients. We decided to investigate the effects of probiotics on
      quality of life and pulmonary exacerbations in children with cystic fibrosis.
      METHODS: In a prospective, randomized, controlled clinical trial, 37 CF patients
      (2-12 years old) were randomly divided into two groups. 20 patients of probiotic
      group took probiotics (2*10(9)CFU/d) for one month while 17 patients of control
      group took placebo capsules. Quality of life was determined using PedsQLTM4.0
      questionnaire at the beginning, then three and six months after completing the
      treatment period. Rate of pulmonary exacerbation in probiotic group patients was
      also evaluated during three months after intervention and compared to the same
      three months of the previous year. Results were analyzed using SPSS (11.5).
      P<0.05 was considered statistically significant. FINDINGS: Significant
      improvement was observed in the mean total score of parent reported quality of
      life among probiotic group patients in comparison with placebo group at 3(rd)
      month (P=0.01), but this was not significant at 6(th) month of probiotic
      treatment. Rate of pulmonary exacerbation was significantly reduced among
      probiotic group (P<0.01). CONCLUSION: Probiotics are considered as useful
      nutritional supplements on reducing number of pulmonary exacerbations and
      improving quality of life in patients with cystic fibrosis. Effects of probiotics
      seem to be temporary and probably continuous ingestion might have more stable
      improving effects on quality of life.

PMID- 24910747
TI  - Neonatal resuscitation in the delivery room from a tertiary level hospital: risk
      factors and outcome.
AB  - OBJECTIVE: Timely identification and prompt resuscitation of newborns in the
      delivery room may cause a decline in neonatal morbidity and mortality. We try to
      identify risk factors in mother and fetus that result in birth of newborns
      needing resuscitation at birth. METHODS: Case notes of all deliveries and
      neonates born from April 2010 to March 2011 in Mahdieh Medical Center (Tehran,
      Iran), a Level III Neonatal Intensive Care Unit, were reviewed; relevant
      maternal, fetal and perinatal data was extracted and analyzed. FINDINGS: During
      the study period, 4692 neonates were delivered; 4522 (97.7%) did not require
      respiratory assistance. One-hundred seven (2.3%) newborns needed resuscitation
      with bag and mask ventilation in the delivery unit, of whom 77 (1.6%) babies
      responded to bag and mask ventilation while 30 (0.65%) neonates needed
      endotracheal intubation and 15 (0.3%) were given chest compressions.
      Epinephrine/volume expander was administered to 10 (0.2%) newborns. In 17
      patients resuscitation was continued for >10 mins. There was a positive
      correlation between the need for resuscitation and following risk factors: low
      birth weight, preterm labor, chorioamnionitis, pre-eclampsia, prolonged rupture
      of membranes, abruptio placentae, prolonged labor, meconium staining of amniotic
      fluid, multiple pregnancy and fetal distress. On multiple regression; low birth
      weight, meconium stained liquor and chorioamnionitis revealed as independent risk
      factors that made endotracheal intubation necessary. CONCLUSION: Accurate
      identification of risk factors and anticipation at the birth of a high-risk
      neonate would result in adequate preparation and prompt resuscitation of neonates
      who need some level of intervention and thus, reducing neonatal morbidity and
      mortality.

PMID- 24910748
TI  - Prevalence of ETV6/RUNX1 Fusion Gene in Pediatric Patients with Acute
      Lymphoblastic Leukemia in Iran.
AB  - OBJECTIVE: ETV6/RUNX1 (also known as TEL/AML1) is the most frequent gene fusion
      in childhood acute lymphoblastic leukemia (ALL). Sixty-three patients were
      enrolled in this study to explore the distribution of this gene in Iranian
      population. METHODS: This study used 63 peripheral blood and bone marrow (PB/BM)
      samples from children with ALL. Immunophenotyping of PB and BM samples were
      performed using flow cytometry to illustrate the lineage. Moreover, reverse
      transcriptase polymerase chain reaction (RT-PCR) technique was used to amplify
      transcripts of leukemia-specific chromosome fusion gene ETV6/RUNX1 and to monitor
      the expression levels of the ETV6/RUNX1 in patients according to Van Dongen et al
      protocol. FINDINGS: On the basis of French-American-British (FAB) classification,
      47 individuals had ALL-L1. The incidence of ETV6/RUNX1 fusion gene in this study
      was 34.9%. The laboratory and clinical features of twenty two ETV6/RUNX1 positive
      ALL cases were similar to those of other studies. The most positive cases of
      ETV6/RUNX1 fusion gene had the early pre B ALL and pre B ALL immunophenotypes.
      CONCLUSION: The ETV6/RUNX1 fusion gene is a common genetic anomaly in Iranian
      childhood ALL patients and the prevalence of the ETV6/RUNX1 fusion gene is
      similar to that of ALL patients in other countries. However early pre B cells
      were the most common type in studied patients.

PMID- 24910749
TI  - Cardiac repolarization changes in the children with breath-holding spells.
AB  - OBJECTIVE: Breath-holding spells are known as benign attacks, frequencies of
      which decrease by the development of the autonomic nervous system. The present
      study aims to compare the electrocardiographic repolarization in children with
      breath-holding spells. METHODS: In this study, QT dispersion, QTc dispersion, T
      peak to T end dispersion, and P wave dispersion of the twelve-lead surface
      electrocardiography of fifty children who had breath-holding spells were measured
      and compared with normal children from April 2011 to August 2012. FINDINGS: Forty
      four (88%) patients had cyanotic spells, while 6 (12%) had pallid spells. QTc
      dispersion was increased in the patients with breath-holding spells (148.2+/
      33.1) compared to the healthy children (132+/-27.3) and the difference was
      statically significant (P = 0.01). Meanwhile, no statistically significant
      differences were observed between the patients and the control subjects regarding
      the other parameters (P > 0.05). CONCLUSION: QTc dispersion was significantly
      increased in the patients with breath-holding spells compared to normal children
      and this is a sign of cardiac repolarization abnormality as well as the increased
      risk of cardiac arrhythmia in patients with breath-holding spells.

PMID- 24910750
TI  - Risk Factors for Hospitalization due to Lower Respiratory Tract Infection in
      Preterm Infants on Palivizumab Prophylaxis.
AB  - OBJECTIVE: To determine the risk factors associated with lower respiratory tract
      infections (LRTI) related hospitalizations in preterm infants receiving
      palivizumab throughout the high season for respiratory syncytial virus (RSV)
      infection. METHODS: Premature infants who were commenced on palivizumab
      prophylaxis during the RSV season were included in the study following parental
      consent. Information on demographic, social, prenatal and postnatal clinical
      characteristics was recorded and risk factors associated with hospitalization
      were evaluated for each patient. FINDINGS: While 234 participants (Group 1,
      92.8%) did not require hospitalization during the study period, 18 patients
      (Group 2, 7.2%) were hospitalized at least once for LRTI during the RSV season.
      The rate of moderate-severe bronchopulmonary dysplasia (BPD) was significantly
      higher in group 2 compared to group 1 (38.9% vs 16.2%; P=0.016). Of the 18
      infants who were hospitalized, 6 (33.3%) tested positive for RSV while the
      remaining 12 patients (66.7%) were negative for RSV. Odds ratio (OR) analysis of
      several risk factors revealed the presence of BPD (OR: 3.28; 95%CI: 1.19-9),
      being from a family with low socioeconomic status (OR: 3.64; 95%CI 1.08-12.3) to
      be associated with a higher likelihood of LRTI-related hospitalization.
      CONCLUSION: Our data demonstrated that RSV is an important LRTI agent and cause
      of hospitalization especially in preterm infants with additional risks such as
      BPD, gestational age of <28 weeks and low socioeconomic status. We suggest that
      improving care conditions and decreased BPD with prematurity would help in
      prevention of LRTI hospitalization.

PMID- 24910751
TI  - Low birth weight and its related risk factors in northeast iran.
AB  - OBJECTIVE: This study was conducted to determine the prevalence of low birth
      weight (LBW) and its related risk factors in an appropriate sample of neonates in
      Shahroud, northeast Iran. METHODS: At this study, a random sample of 1000
      neonates were selected of which 72 neonates were LBWs. We used univariate and
      multivariate logistic regression methods to evaluate the LBW risk factors in LBWs
      compared to normal weight infants. FINDINGS: 7.2% of neonates were LBWs and 6.1%
      born before 37 weeks of gestation. Prematurity, high-risk pregnancy and maternal
      age have significant statistical association with LBW. Odds Ratio (OR) for
      prematurity was 42.82 (95%CI; 21.93-83.57), for high risk pregnancy 2.76 (95%CI;
      1.47-5.19) and for maternal age group more than 35 years in comparison to 19-35
      years age group 0.2 (95%CI; 0.05-0.71). CONCLUSION: Based on this study;
      prematurity and high risk pregnancy were the most important risk factors for LBW.
      There was also a reverse association between maternal age and LBW.

PMID- 24910752
TI  - Recurrent Gallbladder Hydrops and Sclerosing Cholangitis in 11-Year-Old Male with
      Hyper IgM Syndrome.

PMID- 24910753
TI  - Unrevealing of Primary Vesicoureteral Reflux which is Not Harmful for Kidneys in
      Children Should Be Considered as Success.

PMID- 24910754
TI  - Some characteristics of tinea capitis.

PMID- 24910755
TI  - Patent ductus arteriousus device closure in an infant with rubinstein-taybi
      syndrome.

PMID- 24910756
TI  - Prevalence of phototherapy induced hypocalcemia in term neonate.

PMID- 24910757
TI  - Accidental levothyroxine ingestion in a child.

PMID- 24910758
TI  - Gastric perforation associated with congenital diaphragmatic hernia in a neonate.

PMID- 24910759
TI  - Hypophosphatemic rickets and its dental significance.

PMID- 24910760
TI  - Sandifer's Syndrome: a Misdiagnosed and Mysterious Disorder.

PMID- 24910761
TI  - Hypophosphatemic rickets and its dental significance.

PMID- 24910762
TI  - Interpretation of Diagnostic Tests: Likelihood Ratio vs. Predictive Value.

PMID- 24910763
TI  - Peritoneal Dialysis in Neonates with Extremely Low Body Weight at Birth: New
      Modality of Using IV Cannula for Peritoneal Access.

PMID- 24910764
TI  - Increased prevalence of overweight and obesity in birjand adolescents aged 15-18
      years from 2005 to 2012.

PMID- 24910765
TI  - Interchoroid plexus adhesion, a rare anatomical anomaly found with
      neuroendoscope.

PMID- 24910766
TI  - Repurposing human Aurora kinase inhibitors as leads for anti-protozoan drug
      discovery.
AB  - Hesperadin, an established human Aurora B inhibitor, was tested against cultures
      of Trypanosoma brucei, Leishmania major, and Plasmodium falciparum, and was
      identified to be a potent proliferation inhibitor. A series of analogs was
      designed and tested to establish the initial structure-activity relationships for
      each parasite. In this study, we identified multiple non-toxic compounds with
      high potency against T. brucei and P. falciparum with good selectivity. These
      compounds may represent an opportunity for continued optimization.

PMID- 24910767
TI  - Breaking Conjugation: Unusual Regioselectivity with 2-Substituted Allylic
      Substrates in the Tsuji-Trost Reaction.
AB  - eta3-Allyl palladium complexes are key intermediates in Tsuji-Trost allylic
      substitution reactions. It is well known that (eta3-1-aryl-3-alkyl substituted
      allyl)Pd intermediates result in nucleophilic attack at the alkyl substituted
      terminus. In contrast, the chemistry of (eta3-1,2,3-trisubstituted allyl)Pd
      intermediates is relatively unexplored. Herein we probe the regioselectivity with
      1,2,3-trisubstituted allylic substrates in Tsuji-Trost allylic substitution
      reactions. DFT investigation of cationic (eta3-1-Ph-2-B(pin)-3-alkyl
      allyl)Pd(PPh3)2 intermediates predict that nucleophilic attack should occur
      preferentially on anti-allyls rather than the syn-isomers to generate benzylic
      substitution products under Curtin-Hammett conditions. Experimentally, systematic
      studies with 1,2,3-trisubstituted allylic substrates revealed that a Linear Free
      Energy Relationship (LFER) is observed when Charton steric parameters of the C-2
      substituents are plotted against the log of the ratio of regioisomers. Bulkier C
      2 substituents in 1,2,3-trisubstituted eta3-allyl palladium intermediates provide
      stronger preference for nucleophilic attack at anti-oriented benzylic termini.
      Additionally, the geometry of 1,4-elimination products supports the presence of
      anti-allyl palladium intermediates.

PMID- 24910768
TI  - Pd(Quinox)-Catalyzed Allylic Relay Suzuki Reactions of Secondary Homostyrenyl
      Tosylates via Alkene-Assisted Oxidative Addition.
AB  - Pd-catalyzed allylic relay Suzuki cross-coupling reactions of secondary alkyl
      tosylates, featuring a sterically-hindered oxidative addition and precise control
      of beta-hydride elimination, are reported. The identification of a linear free
      energy relationship between the relative rates of substrate consumption and the
      electronic nature of the substrate alkene suggests that the oxidative addition
      requires direct alkene involvement. A study of the effect of chain length on the
      reaction outcome supports a chelation-controlled oxidative addition.

PMID- 24910769
TI  - Measuring symptoms as a critical component of drug development and evaluation in
      hematological diseases.
AB  - With the rapid development of new therapies for patients with hematological
      malignancies, there is an increasing need for patient report of symptom status
      during all phases of drug testing. The patient's perspective on new treatments
      reflects treatment tolerability as well as symptom benefit, and may assist
      patients and clinicians in choosing treatments. Inclusion of patient-reported
      outcomes, more common in solid-tumor than hematological trials, provides early
      information about symptoms to guide decisions about appropriate dosing and
      supportive care needs. We provide a historical overview of the use of patient
      reported outcomes and symptom assessment in solid-tumor and hematological drug
      development, and offer recommendations about methodological issues in the
      monitoring of symptoms in the drug development process in hematological clinical
      trials.

PMID- 24910770
TI  - Myofiber branching rather than myofiber hyperplasia contributes to muscle
      hypertrophy in mdx mice.
AB  - BACKGROUND: Muscle hypertrophy in the mdx mouse model of Duchenne muscular
      dystrophy (DMD) can partially compensate for the loss of dystrophin by
      maintaining peak force production. Histopathology examination of the hypertrophic
      muscles suggests the hypertrophy primarily results from the addition of
      myofibers, and is accompanied by motor axon branching. However, it is unclear
      whether an increased number of innervated myofibers (myofiber hyperplasia)
      contribute to muscle hypertrophy in the mdx mice. METHODS: To better understand
      the cellular mechanisms of muscle hypertrophy in mdx mice, we directly compared
      the temporal progression of the dystrophic pathology in the extensor digitorum
      longus (EDL) muscle to myofiber number, myofiber branching, and innervation, from
      3 to 20 weeks of age. RESULTS: We found that a 28% increase in the number of
      fibers in transverse sections of muscle correlated with a 31% increase in
      myofiber branching. Notably, the largest increases in myofiber number and
      myofiber branching occurred after 12 weeks of age when the proportion of
      myofibers with central nuclei had stabilized and the mdx mouse had reached
      maturity. The dystrophic pathology coincided with profound changes to innervation
      of the muscles that included temporary denervation of necrotic fibers,
      fragmentation of synapses, and ultra-terminal axon sprouting. However, there was
      little evidence of synapse formation in the mdx mice from 3 to 20 weeks of age.
      Only 4.4% of neuromuscular junctions extended ultra-terminal synapses, which
      failed to mature, and the total number of neuromuscular junctions remained
      constant. CONCLUSIONS: Muscle hypertrophy in mdx mice results from myofiber
      branching rather than myofiber hyperplasia.

PMID- 24910771
TI  - Characteristics and management of sublingual allergen immunotherapy in children
      with allergic rhinitis and asthma induced by house dust mite allergens.
AB  - BACKGROUND: Allergen immunotherapy is a recognised intervention in patients with
      allergies not responding to standard pharmacotherapy or in whom pharmacotherapy
      is contraindicated. We describe the sublingual immunotherapy (SLIT) regimens used
      in children and adolescents with house dust mite (HDM) respiratory allergies in
      France and assess the efficacy and safety of this treatment. METHODS: This was a
      sub-analysis of paediatric patients included in a previous retrospective,
      observational, multicentre study. Inclusion criteria were: age 5-17 years;
      respiratory allergy and proven sensitisation to HDM; at least 2 years follow-up
      after SLIT initiation. The following data were recorded at SLIT initiation:
      clinical characteristics; sensitisation profile; concomitant symptomatic
      medications; details of SLIT protocol. During follow-up and at the end of
      treatment the following data were recorded: any changes to SLIT treatment; any
      changes to symptomatic medications; symptom progression; adverse events. SLIT
      efficacy, patient compliance and satisfaction, and safety were assessed. RESULTS:
      736 paediatric patients were included in this analysis. Most patients (95.5%) had
      allergic rhinitis, which was moderate to severe persistent in 62.8%. Allergic
      asthma was present in 64.0% and was mild to moderate persistent in 52.7% of these
      patients. The majority of patients had rhinitis with asthma (59.5%). Three
      hundred and seventy five (62.3%) patients were polysensitised. Compliance was
      good in 86.5% of patients and SLIT was effective in 83.8%. Symptoms of rhinitis
      and asthma were improved in 64.6% and 64.3% of patients, respectively. A decrease
      in symptomatic medication was observed following SLIT initiation in patients with
      rhinitis and/or asthma. SLIT was well tolerated with mainly local reactions
      reported. CONCLUSIONS: HDM SLIT appears to be effective in children and
      adolescents with rhinitis and/or asthma due to HDM allergens, with no
      tolerability issues and similar benefits as in adults.

PMID- 24910772
TI  - Intestinal allergic inflammation in birch pollen allergic patients in relation to
      pollen season, IgE sensitization profile and gastrointestinal symptoms.
AB  - BACKGROUND: Birch pollen allergic patients frequently experience gastrointestinal
      upset accompanied by a local allergic inflammation in the small intestine
      especially during the pollen season. However, it is not known if the GI pathology
      is connected to the subjective symptoms of the patient. The objective of this
      study was to evaluate the immune pathology of the duodenal mucosa and the serum
      IgE antibody profiles in birch pollen allergic patients in relation to their
      gastrointestinal symptoms, during and outside the birch pollen season. METHODS:
      Thirty-two patients with birch pollen allergy and sixteen healthy controls were
      enrolled in the study. Twenty allergic patients had gastrointestinal symptoms and
      twelve did not. All participants underwent an allergy investigation and
      gastroscopy with duodenal biopsy. The duodenal biopsies were retrieved during the
      pollen season (May-June) and off-season (November-March). The biopsies were
      immunostained for mast cells (IgE and tryptase), eosinophils, T cells (CD3), and
      dendritic cells (CD11c). Pollen-specific IgE antibodies were determined by
      ImmunoCAP and component microarray (ISAC). RESULTS: Patients in both pollen
      allergic groups showed similar degree of intestinal allergic inflammation during
      the pollen season regardless of gastrointestinal symptoms. The eosinophils, mast
      cells and dendritic cells were increased in the mucosa. Patients with
      gastrointestinal symptoms had significantly elevated IgE antibodies to birch
      (rBet v 1), hazelnut (rCor a 1), and apple (rMal d1) during the pollen season.
      CONCLUSIONS: Patients allergic to birch pollen have clear signs of an ongoing
      allergic inflammation in their intestinal mucosa, which is aggravated during the
      pollen season. The magnitude of the allergic intestinal inflammation is not
      associated with subjective gastrointestinal symptoms of the individual patient.

PMID- 24910773
TI  - Unifying the analysis of high-throughput sequencing datasets: characterizing RNA
      seq, 16S rRNA gene sequencing and selective growth experiments by compositional
      data analysis.
AB  - BACKGROUND: Experimental designs that take advantage of high-throughput
      sequencing to generate datasets include RNA sequencing (RNA-seq), chromatin
      immunoprecipitation sequencing (ChIP-seq), sequencing of 16S rRNA gene fragments,
      metagenomic analysis and selective growth experiments. In each case the
      underlying data are similar and are composed of counts of sequencing reads mapped
      to a large number of features in each sample. Despite this underlying similarity,
      the data analysis methods used for these experimental designs are all different,
      and do not translate across experiments. Alternative methods have been developed
      in the physical and geological sciences that treat similar data as compositions.
      Compositional data analysis methods transform the data to relative abundances
      with the result that the analyses are more robust and reproducible. RESULTS: Data
      from an in vitro selective growth experiment, an RNA-seq experiment and the Human
      Microbiome Project 16S rRNA gene abundance dataset were examined by ALDEx2, a
      compositional data analysis tool that uses Bayesian methods to infer technical
      and statistical error. The ALDEx2 approach is shown to be suitable for all three
      types of data: it correctly identifies both the direction and differential
      abundance of features in the differential growth experiment, it identifies a
      substantially similar set of differentially expressed genes in the RNA-seq
      dataset as the leading tools and it identifies as differential the taxa that
      distinguish the tongue dorsum and buccal mucosa in the Human Microbiome Project
      dataset. The design of ALDEx2 reduces the number of false positive
      identifications that result from datasets composed of many features in few
      samples. CONCLUSION: Statistical analysis of high-throughput sequencing datasets
      composed of per feature counts showed that the ALDEx2 R package is a simple and
      robust tool, which can be applied to RNA-seq, 16S rRNA gene sequencing and
      differential growth datasets, and by extension to other techniques that use a
      similar approach.

PMID- 24910774
TI  - Chemical patterning on preformed porous silicon photonic crystals: towards
      multiplex detection of protease activity at precise positions?Electronic
      supplementary information (ESI) available: SEM images, XPS result and more
      optical reflectivity data. See DOI: 10.1039/c4tb00281dClick here for additional
      data file.
AB  - Porous silicon (PSi) rugate filters modified with alkyne-terminated monolayers
      were chemically patterned using a combination of photolithography of photoresist
      and click chemistry. Two chemical functionalities were obtained by conjugating,
      via click reactions, ethylene glycol moieties containing two different terminal
      groups to discrete areas towards the exterior of a PSi rugate filter. The
      patterning of biological species to the functionalized surface was demonstrated
      through the conjugation of fluorescein isothiocyanate labelled bovine serum
      albumin (FITC-BSA). Fluorescence microscopy showed selective positioning of FITC
      BSA at discretely functionalized areas. Meanwhile, the optical information from
      precisely defined positions on the patterned surface was monitored by optical
      reflectivity measurements. The optical measurements revealed successful step-wise
      chemical functionalization followed by immobilization of gelatin. Multiplex
      detection of protease activity from different array elements on the patterned
      surface was demonstrated by monitoring the blue shifts in the reflectivity
      spectra resulted from the digestion of gelatin by subtilisin. Precise information
      from both individual elements and average population was acquired. This technique
      is important for the development of PSi into a microarray platform for highly
      parallel biosensing applications, especially for cell-based assays.

PMID- 24910775
TI  - Micro-RNAs, New performers in multiple myeloma bone marrow microenvironment.
AB  - The established interaction between multiple myeloma cells and bone marrow
      microenvironment components provides malignant cells with various survival,
      growth and drug resistance signals. As a new concept, identification of miRNAs
      and their related gene/protein targets, signaling molecules and pathways in the
      context of bone marrow microenvironment will help understanding more deeply the
      pathogenesis of the disease and possible mechanisms underlying environment
      induced drug resistance. Recent studies suggest that bone marrow stromal cells
      can modulate some miRNAs (miR-21, miR-15a/16) in multiple myeloma cells through
      direct adhesion, cytokine secretion or transfer of miRNA-containing exosomes,
      however; the specific miRNA targets are not clear. In spite of a remarkable
      progress in understanding myeloma biology and therapy, the disease persists to be
      hard to treat. This review will discuss the most recent findings on miRNAs
      expression and function in the context of bone marrow microenvironment
      highlighting the miRNAs as potential therapeutic targets in multiple myeloma. 

PMID- 24910776
TI  - Greenhouse Gases Life Cycle Assessment (GHGLCA) as a decision support tool for
      municipal solid waste management in Iran.
AB  - BACKGROUND: One of the most problems in developing countries is the integrated
      waste management and the effects on Greenhouse Gases (GHG) emission, Life Cycle
      Assessment (LCA) is used in this paper as a decision supporting tool in planning
      Municipal Solid Waste (MSW) managements. METHODS: In this paper the EPA's Waste
      Reduction Model (WARM) that provide GHG emission factors for waste stream
      components that are based on life Cycle Inventory (LCI) framework were used and
      The MSW management methods comprised in seven scenarios. RESULTS: The amount of
      GHG which was generated from Iran's waste sector estimated about 17836079 Metric
      Tons of Carbon dioxide Equivalents (MT CO2e) in this study. The lowest amount of
      GHG was generated by LFG capture system with energy recovery (557635 MT CO2e),
      while Incineration of materials being sent to landfill (1756823 MT CO2e),
      Landfill Gas (LFG) capture system with flaring (2929150 MT CO2e) and Improved
      source reduction and recycling (4780278 MT CO2e) emitted fewer GHG than the other
      scenarios. Lowest levels of gross energy consumption occur in source reduction
      with recycling and composting (-89356240 Mega British Thermal Unit, M BTU),
      recycling and composting (-86772060 M BTU) as well as Improved source reduction
      with recycling and composting (-54794888 M BTU). CONCLUSIONS: It appears that
      recycling and composting each offer significant GHG emissions and energy
      consumption reductions (scenarios 4, 5 and 6). Upon of the GHG emission and
      energy consumption results concluded that improved source reduction and recycling
      scenario has been the Balanced and appropriate technology for handling the solid
      waste streams in municipalities.

PMID- 24910777
TI  - Fusarisetins: Structure-function studies on a novel class of cell migration
      inhibitors.
AB  - Herein, we report the effects of fusarisetin A on cell morphology focusing in
      particular on actin and microtubules dynamics. We also report the synthesis and
      structure-function studies of a designed library of synthetic fusarisetins in
      cell-based assays.

PMID- 24910778
TI  - Stereoselective Intramolecular Cyclopropanation of alpha-Diazoacetates via Co(II)
      Based Metalloradical Catalysis.
AB  - Co(II) complexes of D2-symmetric chiral porphyrins have been proven to be
      effective metalloradical catalysts for the asymmetric intramolecular
      cyclopropanation of allyl alpha-diazoacetates. 4-(Dimethylamino)pyridine (DMAP),
      through positive trans effect, plays an important role in the enhancement of the
      asymmetric induction for the intramolecular cyclopropanation process. This
      metalloradical catalytic system is suitable for cyclopropanation of allyl alpha
      diazoacetates with varied functional groups and substitution patterns, producing
      bicyclic products with complete diastereocontrol and good enantiocontrol.

PMID- 24910780
TI  - The Sensitivity Analysis for the Flow Past Obstacles Problem with Respect to the
      Reynolds Number.
AB  - In this paper, numerical sensitivity analysis with respect to the Reynolds number
      for the flow past obstacle problem is presented. To carry out such analysis, at
      each time step, we need to solve the incompressible Navier-Stokes equations on
      irregular domains twice, one for the primary variables; the other is for the
      sensitivity variables with homogeneous boundary conditions. The Navier-Stokes
      solver is the augmented immersed interface method for Navier-Stokes equations on
      irregular domains. One of the most important contribution of this paper is that
      our analysis can predict the critical Reynolds number at which the vortex shading
      begins to develop in the wake of the obstacle. Some interesting experiments are
      shown to illustrate how the critical Reynolds number varies with different
      geometric settings.

PMID- 24910779
TI  - Triple helix-interacting proteins and cancer.
AB  - While most naturally occurring DNA and RNA adopt the now quite familiar double
      helix structure, certain sequences can under the appropriate conditions adopt a
      three-stranded, triple-helical structure. Both intramolecular and intermolecular
      triplexes have been described. Evidence for the existence of triplex structures
      in vivo is limited, although cellular proteins have been identified that avidly
      and specifically interact with such species. The postulated roles of triplexes
      and the proteins that interact with them in cancer and their potential utility as
      diagnostic markers are discussed in this review.

PMID- 24910781
TI  - Perception of medical university members from nutritional health in the quran.
AB  - BACKGROUND: Desirable health is impossible without good nutrition, and Allah has
      addressed us on eating foods in 118 verses. OBJECTIVES: This study aimed to
      describe the medical university faculty members' perceptions of nutritional
      health in the Quran, revealing the important role of faculty members. MATERIALS
      AND METHODS: This qualitative study was conducted with a phenomenological
      approach. Homogeneous sampling was performed in a final sample size of 16
      subjects. The Colaizzi's phenomenological method was applied for data analysis.
      RESULTS: Three main categories were extracted from the data analysis, including
      the importance of nutrition in the Quran (referring to certain fruits, vegetables
      and foods, illustrating and venerating the heavenly ones, nutritional
      recommendations, revealing the healing power of honey and the effects of fruits
      and vegetables on physical and social health); reasons of different foods being
      lawful (halal) and unlawful (haram) (religious slaughter, wine, meats,
      consequences of consuming haram materials, general expression of halal and haram
      terms); and fasting (fasting and physical health, fasting and mental health).
      CONCLUSIONS: What has been mentioned in the Quran is what scientists have
      achieved over the time, since the Quran is governed by logic. Although we do not
      know the reasons for many things in the Quran, we consider it as the foundation.

PMID- 24910782
TI  - Ankylosing spondylitis in iran; late diagnosis and its causes.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic destructive and inflammatory
      disease of the axial skeleton manifested by back pain and progressive stiffness
      of the spine. OBJECTIVES: The aim of the present cross-sectional study was to
      evaluate and identify factors leading to delayed diagnosis of AS in Iranian
      patients. PATIENTS AND METHODS: Sixty patients, (53 males, 7 females) with a
      diagnosis of AS according to the modified New York criteria were recruited.
      Diagnosis delay was defined as the interval between a patient's first
      spondyloarthritic symptoms [inflammatory back pain (IBP), inflammatory arthritis,
      enthesopathy and uveitis] and a correct diagnosis of AS. RESULTS: The average age
      of patients at diagnosis of AS was 36.4 +/- 4.5 years and the average of delay in
      diagnosis was 6.2 +/- 3.5 years. The most common diagnosis at the first visit was
      disc herniation (68.3%). Delay in diagnosis of Human Leukocyte Antigen (HLA-B27)
      positive and negative patients were 4.6 +/- 2.2 years and 10.1 +/- 3.2 years,
      respectively (P = 0.0001). Diagnosis delay in patients with morning stiffness and
      IBP were significantly shorter than that of patients without these symptoms (P =
      0.0001 and P = 0.001, respectively). Patients with uveitis had the shortest
      diagnosis delay (P = 0.02). The Bath Ankylosing spondylitis disease activity
      index (BASDAI) was not significantly different in early (< 3years) and late (>
      3years) diagnosis (3.3 +/- 0.9 and 3.6 +/- 0.7, respectively) (P = 0.18), but the
      Both ankylosing spondylitis functional index (BASFI) was significantly different
      between them (3.3 +/- 1.0 and 4.1 +/- 0.7 respectively) (P = 0.001). CONCLUSIONS:
      In this study, delay in diagnosis was similar to other studies. Educating
      physicians to careful history taking especially in the case of IBP, non
      musculoskeletal symptoms such as uveitis and precise physical examination are
      important in early diagnosis.

PMID- 24910783
TI  - Iranian nurses' perception of patient safety culture.
AB  - BACKGROUND: In recent decades, patient safety has become a high priority health
      system issue, due to the high potential of occurring adverse events in health
      facilities. OBJECTIVES: This study was aimed to survey patient safety culture in
      2 Iranian educational hospitals. MATERIALS AND METHODS: In a descriptive, cross
      sectional survey, a hospital survey on patient safety culture, was used in two
      teaching hospitals in Yazd, Iran during 2012. Study population was comprised of
      the same hospitals' nurses. Stratified-random sampling method was used and
      distributed among a total of 340 randomly-selected nurses from different units.
      From all distributed questionnaires, 302 ones were answered completely and
      afterwards analyzed using SPSS 17. Dimensional- and item-level positive scores
      were used for results reporting. Additionally descriptive statistics (mean and
      standard deviation), independent sample t-test and ANOVA were sued for data
      analyzing. RESULTS: Research findings demonstrated that both hospitals had low to
      average scores in all dimensions of patient safety culture. Non-punitive response
      to error, staffing and frequency of events reported had the lowest positive
      scores of patient safety dimensions with scores 15.26, 19.26, 16.65, 30 and
      32.87, 31.10 respectively in Shahid Sadoughi and Shahid Rahnemoon Hospitals. Also
      only 29.20 and 28.80 percent of nurses in Shahid Sadoughi and Shahid Rahnemoon
      Hospitals, respectively, evaluated the patient safety grade of their hospital as
      "excellent" and "very good". Indeed, the studied hospitals had a statistical
      difference in 3 dimensions of patient safety culture (frequency of events
      reported, organizational learning and staffing). (P <= 0.05). CONCLUSIONS: Our
      study results were indicating of the challenge of weak patient safety culture, in
      educational hospitals. Therefore, the issue should be integrated to all policy
      makers and managerial initiatives in our health system, as a top priority.

PMID- 24910784
TI  - Sociodemographic characteristics of pregnant women exposed to domestic violence
      during pregnancy in an Iranian setting.
AB  - BACKGROUND: Domestic violence refers to any type of physical, sexual, and
      psychological abuse enforced in the setting of familial relationships. Domestic
      violence has a significant relationship with poor outcome among pregnant women.
      Success in resolving this social phenomenon rests on accurate assessment of the
      society and the factors associated with violence in that specific community.
      OBJECTIVES: The present study was conducted to assess the demographic
      characteristics of pregnant women exposed to different types of domestic violence
      during pregnancy in Iranian setting. PATIENTS AND METHODS: This is a descriptive
      analytic, cross-sectional study. Sampling was done with convenience sampling
      method. in the current study, 301 pregnant women aged 15-45 years of Iranian
      nationality who were referred to the hospital for delivery or abortion,
      regardless of the gestational age, were selected as the subjects. Data collection
      tools consisted of a sociodemographic questionnaire and a violence checklist.
      Violence was assessed using Revised Conflict Tactics Scale (CTS2). Data were
      analyzed using descriptive and analytic statistics on SPSS version 16 (SPSS,
      Chicago, IL, USA) and STATA version 10. The characteristics of the participants
      were presented as mean +/- SD or number and percentage. Differences between
      variables were determined by the chi2 test, and multivariate logistic regression.
      P < 0.05 was considered significant. RESULTS: According to the findings, 34.56%
      of participants had experienced psychological violence, 28.24% physical violence,
      and 3.65% sexual violence. Multivariate logistic regression revealed a
      statistically significant relationship only in the case of physical violence and
      history of penal conviction for partner (Adjusted Odds Ratio (AOR) = 12.60) and a
      patriarchal household (AOR = 16.75). CONCLUSIONS: As domestic violence is greatly
      influenced by the customs and cultures of each community, no single strategy can
      be adopted to resolve it universally. Simultaneously, it is necessary to adopt
      comprehensive measures to control factors associated with domestic violence in
      the healthcare, judiciary, and the educational systems in order to prevent and
      curb this social challenge.

PMID- 24910785
TI  - Early surfactant therapy with nasal continuous positive airway pressure or
      continued mechanical ventilation in very low birth weight neonates with
      respiratory distress syndrome.
AB  - BACKGROUND: Various strategies have been suggested for the treatment of
      respiratory distress syndrome (RDS). OBJECTIVES: The aim of this study was to
      compare the efficacies of two common methods of RDS management among neonates
      with low birth weight. PATIENTS AND METHODS: A cohort study was conducted on 98
      neonates with definite diagnosis of RDS during 2008-2009. The neonates were
      divided into two groups by a blinded supervisor using simple randomization (odd
      and even numbers). Forty-five cases in the first group were treated with
      intubation, surfactant therapy, extubation (INSURE method) followed by nasal
      continuous positive airway pressure (N.CPAP) and 53 cases in the second group
      underwent intubation, surfactant therapy followed by mechanical ventilation (MV).
      RESULTS: Five (11.1%) cases in the first group and 23 (43%) cases in the second
      group expired during the study. The rates of MV dependency among cases with
      INSURE failure and cases in the MV group were 37% and 83%, respectively (P <
      0.001). Birth weight (BW) (P = 0.017), presence of retinopathy of prematurity (P
      = 0.022), C/S delivery (P = 0.029) and presence of lung bleeding (P = 0.010)
      could significantly predict mortality in the second group, although only BW (P =
      0.029) had a significant impact on the mortality rate in the first group.
      Moreover, BW was significantly related to the success rate in the first group (P
      = 0.001). CONCLUSIONS: Our findings demonstrated that INSURE plus NCPAP was more
      effective than the routine method (permanent intubation after surfactant
      prescription). In addition, the lower rates of mortality, MV dependency, duration
      of hospitalization, and complications were observed in cases treated with the
      INSURE method compared to the routine one.

PMID- 24910786
TI  - Characterization of Diarrheagenic Antimicrobial Resistant Escherichia coli
      Isolated From Pediatric Patients in Tehran, Iran.
AB  - BACKGROUND: Acute infectious diarrhea is one of the most important causes of
      morbidity and mortality worldwide. OBJECTIVES: The objective of this study was to
      characterize antimicrobial resistant diarrheagenic Escherichia coli strains
      isolated from diarrheic children in Tehran, IR Iran. PATIENTS AND METHODS: In
      total, 550 stool samples from diarrheic pediatric patients, aged less than 60
      months, were collected and immediately transferred to the laboratory. Isolation
      and identification of E. coli strains was done using bacteriological methods.
      Antimicrobial susceptibility testing was performed using the disk diffusion
      technique. Multiplex PCR was used to detect aadA1, tetA, tetB, dfrA1, qnr, aac
      (3)-IV, sul1, blaSHV, CITM, cat1, and cmlA antibiotic resistance genes. RESULTS:
      From the total of 550 fecal samples examined, 154 samples (28%) were positive for
      diarraheagenic E. coli. High rates of antibiotic resistance were seen against
      penicillin ?100%), ampicillin ?89.6%? and tetracycline ?83.1%?. Resistance
      against ciprofloxacin was low ?28.6%?. The prevalence of different resistance
      genes in the studied strains varied from 96.10% for aadA1 gene to 40.25% for sul1
      gene. The frequencies of aadA1, tetA, tetB, dfrA1, qnr, aac(3)-IV, sul1, blaSHV,
      CITM, cat1, and cmlA genes were 96.10%, 85.06%, 84.41%, 51.94%, 72.07%, 54.54%,
      40.25%, 57.79%, 90.25%, 59.74% and 60.38%, respectively. CONCLUSIONS: Our results
      indicated that antibiotic resistance is increasing in diarraheagenic E. coli
      strains in Iran. It is imperative to develop strategies for prevention and
      control of resistant organisms. Changes in patterns of resistance against
      commonly used antibiotics in Iran indicate that an applied surveillance system
      and introduction of guidelines for appropriate antibiotic prescription are
      necessary.

PMID- 24910787
TI  - The performance of the ethics committees in teaching hospitals affiliated with
      mashhad university of medical sciences.
AB  - BACKGROUND: During the last three decades, ethics committees have been formed
      with a growing trend. These committees have a satisfactory and effective impact
      on the pattern of patient care and its performance. The medical ethics committee
      is considered one of the most active committees in hospitals, having the aim of
      providing necessary approaches for the optimal use of the findings in empirical
      science and diagnostic treatment and observance of Islamic noble values in
      performing medical affairs. OBJECTIVES: The aim of this study is to assess the
      performance of the ethics committees, in the teaching hospitals affiliated with
      Mashhad University of Medical Sciences, in Mashhad. PATIENTS AND METHODS:
      Subjects of this study include teaching hospitals in Mashhad, affiliated with
      Mashhad University of Medical Sciences and the tool used in gathering the data
      was a questionnaire, completed based on the information provided by the
      proceedings of the meetings held by the ethics committees. Also, for the purpose
      of gathering the suggestions, specifically on the improvement of the performance,
      a meeting was held with the representatives from hospitals' ethics committees.
      During the meeting, work reports were presented and recommendations made, based
      on those presentations. . RESULTS: Findings of the present study suggest that all
      hospitals under study, have an ethics committee, of which 85.7% operate in
      combination with other committees. The composition of the members of the
      committees, in 57.1% of the hospitals, was based on the guidelines for hospital
      evaluation. CONCLUSIONS: For the performance of the medical ethics committees to
      improve, it is recommended that the hospital administration and evaluation
      section, hold regular meetings and oblige members to participate more actively.

PMID- 24910788
TI  - Comparing GlideScope Video Laryngoscope and Macintosh Laryngoscope Regarding
      Hemodynamic Responses During Orotracheal Intubation: A Randomized Controlled
      Trial.
AB  - BACKGROUND: To determine if the GlideScope(r) videolaryngoscope (GVL) could
      attenuate the hemodynamic responses to orotracheal intubation compared with
      conventional Macintosh laryngoscope. OBJECTIVES: The aim of this relatively large
      randomized trial was to compare the hemodynamic stress responses during
      laryngoscopy and tracheal intubation using GVL versus MCL amongst healthy adult
      individuals receiving general anesthesia for elective surgeries. PATIENTS AND
      METHODS: Ninety five healthy adult patients with American Society of
      Anesthesiologists physical status class I or II that were scheduled for elective
      surgery under general anesthesia were randomly allocated to either Macintosh or
      GlideScope arms. All patients received a standardized protocol of general
      anesthesia. Hemodynamic changes associated with intubation were recorded before
      and at 1, 3 and 5 minutes after the intubation. The time taken to perform
      endotracheal intubation was also noted in both groups. RESULTS: Immediately
      before laryngoscopy (pre-laryngoscopy), the values of all hemodynamic variables
      did not differ significantly between the two groups (All P values > 0.05). Blood
      pressures and HR values changed significantly over time within the groups. Time
      to intubation was significantly longer in the GlideScope (15.9 +/- 6.7 seconds)
      than in the Macintosh group (7.8 +/- 3.7 sec) (P< 0.001). However, there were no
      significant differences between the two groups in hemodynamic responses at all
      time points. CONCLUSIONS: The longer intubation time using GVL suggests that the
      benefit of GVL could become apparent if the time taken for orotracheal intubation
      could be decreased in GlideScope group.

PMID- 24910789
TI  - Evaluation of FcgammaRIIIB-NA1/NA2 Polymorphism in Visceral Leishmaniasis.
AB  - BACKGROUND: Several lines of evidence demonstrating that innate and adaptive
      immunity play important roles in the defense against visceral leishmaniasis (VL).
      A polymorphism within the FcgammaRIIIB gene can lead to the expression of three
      variants of NA1, NA2, and the combined one (NA1/NA2) which alters affinity of IgG
      to its receptor. OBJECTIVES: The main aim of this study was to evaluate the
      FcgammaRIIIB-NA1/NA2 polymorphism in the FcgammaRIIIB gene of VL patients in
      comparison to healthy controls. PATIENTS AND METHODS: In this cross-sectional
      study, three groups; 54 seropositive patients with clinical presentation of VL
      (group 1), 104 seropositive patients without clinical presentation (group 2), and
      104 healthy controls (group 3) were evaluated with respect to the FcgammaRIIIB
      NA1/NA2 polymorphism using a PCR-SSP method. The titration of anti-leishmania
      antibodies was analyzed using an immunoflorescence technique. RESULTS: Our
      results indicated that polymorphisms within the FcgammaRIIIB gene (that lead to
      the expression of the NA1/NA2 isoforms) are significantly associated with VL. The
      results demonstrated that the genotype heterozygotic for FcgammaRIIIB-NA1/NA2
      expression was significantly increased in VL patients, group 1 when compared to
      groups 2 and 3. Conversely, there is a decrease in homozygous NA1 and NA2
      genotypes in VL patients; however, the overall frequency of NA1 and NA2 alleles
      appear similar across the three cohorts examined. CONCLUSIONS: According to our
      results, it is likely that the increased frequency of the FcgammaRIIIB-NA1/NA2
      genotype is associated with impaired immune responses against VL and its
      subsequent clearance from the patient.

PMID- 24910790
TI  - CCR5 on the NK Cells and its Ligand (RANTES) Expressions are Disrupted in South
      Eastern Iranian Patients With Chronic Hepatitis B Infection.
AB  - BACKGROUND: CCR5 is a receptor for CCL3 (MIP-1 alpha), CCL4 (MIP-1 alpha) and
      CCL5 (regulated on activation normal T cell expressed and secreted (RANTES)) and
      play important roles in recruitment of NK cells to the HBV infected liver.
      OBJECTIVES: The main purpose of this study was to investigate the expression
      levels of CCR5 on the NK cells and also serum levels of RANTES in chronic HBV
      infected (CHI) patients. MATERIALS AND METHODS: In this descriptive study 63 CHI
      patients and 96 healthy controls were evaluated regarding CCR5 expression on the
      NK cells and serum levels of RANTES using flow cytometry and ELISA techniques,
      respectively. Real-Time PCR technique also was used for HBV-DNA quantification.
      RESULTS: The results revealed that CCR5 expressing NK cells and serum levels of
      RANTES were decreased significantly in the CHI patients in compare to healthy
      control. CONCLUSIONS: Based on the results it can be concluded that NK cells of
      Iranian CHI patients are unable to express adequate levels of CCR5 and expression
      levels of RANTES by immune cells also are defected in CHI patients, hence, the
      migration of NK cells to the infected hepatocytes and HBV eradication from the
      cells is interrupted.

PMID- 24910791
TI  - Randomized comparison of nylon versus absorbing polyglactin 910 for fascial
      closure in caesarean section.
AB  - BACKGROUND: Regardless of numerous advances in surgical techniques, selection of
      the best technique to sew up wounds and the best suture material are still
      controversial. Several postoperative complications, including wound infection,
      stitched wound, chronic incision pain, wound dehiscence and hernia stitches
      result from many factors such as used suture material. OBJECTIVES: The aim of the
      present study was to investigate the complications of pfannenstiel incision and
      nylon/ polyglactin 910 sutures utilization in patients undergoing c-section
      cesarean. PATIENTS AND METHODS: This clinical trial was conducted on 120 women
      who underwent caesarean section at Imam-Ali hospital in Zabol, Iran. In this
      study, patients were equally divided into two groups of 60 people (50% in nylon
      suture and 50% in polyglactin 910 sutures). Patients of the two groups were
      investigated by a gynecologist 24-48 hours after the operation, a week later and
      on the sixth month of surgery. Moreover, time of wound dehiscence and treatment
      duration, the level of sinus infection, chronic incision pain and incision hernia
      were studied. The results were analyzed by SPSS software. P <= 0.05 was
      considered as statistically significant. RESULTS: One hundred and twenty patients
      undergoing a cesarean section at Imam-Ali hospital in Zabol were recruited into
      the study, 60 in the Nylon group and 60 in Polyglactin 910group. Our data
      demonstrated a statistically higher incidence of suture sinus and chronic
      incision pain in the nylon group (P < 0.05). No statistically significant
      difference in wound stitch and incision hernia was demonstrated between the
      suture groups. CONCLUSIONS: The results of our trial did not demonstrate a
      significant difference between absorbing polyglactin 910 (PDS) and nylon
      regarding incision hernia, wound infection and wound dehiscence. However,
      subjects sutured with PDS were less likely to experience chronic incision pain
      and wound stitch. Therefore, PDS appears to be the optimal choice for fascial
      closure after cesarean section.

PMID- 24910792
TI  - Prioritizing the Determinants of Social-health Inequality in Iran: A Multiple
      Attribute Decision Making Application.
AB  - BACKGROUND: One of the main challenges of healthcare systems of developing
      countries is health inequality. Health inequality means inequality in
      individuals' ability and proper functioning, resulting in inequality in social
      status and living conditions, which thwarts social interventions implemented by
      the government. OBJECTIVES: This study aimed to determine and prioritize the
      social determinants of health inequality in Iran. MATERIALS AND METHODS: This was
      a mixed method study with two phases of qualitative and quantitative research.
      The study population consisted of experts dealing with social determinants of
      health. A purposive, stratified and non-random sampling method was used. Semi
      structured interviews were conducted to collect qualitative data along with a
      multiple attribute decision making method for the quantitative phase of the
      research in which the TOPSIS technique was employed for prioritization. The
      qualitative findings were entered into NVivo for analysis, as were the
      quantitative data entered into MATLAB software. RESULTS: The results approved the
      suitability of the conceptual framework of social determinants of health
      suggested by the WHO (world health organization) for studying social determinants
      of health inequality; however, this framework general and theoretical rather than
      a guideline for practice. Thus, in this study, 15 themes and 31 sub-themes were
      determined as social determinants of social health inequality in Iran. Based on
      the findings of the quantitative phase of our research, socioeconomic status,
      living facilities such as housing, and social integrity had the greatest effect
      on decreasing health inequality. CONCLUSIONS: A major part of the inequality in
      health distribution is avoidable because they are mostly caused by adjustable
      factors like economic conditions, educational conditions, employment, living
      facilities, etc. As in the majority of developing countries the living and health
      conditions are the same as Iran, the findings of this study may be applicable for
      other developing countries.

PMID- 24910793
TI  - Personality factors underlying suicidal behavior among military youth.
AB  - BACKGROUND: Suicidal behavior is one the most significant mental health problems
      in the military. Militaries are closed systems that operate in particular
      situations. Military service is associated with certain stressful conditions. On
      this basis, there is likely of trauma in the military environment. Measures of
      suicidal behavior are pathologically complex. A range of biological,
      psychological, social, and institutional factors are involved in the incidence
      and prevalence of these behaviors. OBJECTIVES: One of the underlying factors in
      suicidal behavior is individuals' personality. PATIENTS AND METHODS: The study
      population comprised of the Iranian Armed Forces. To recruit the sample of the
      research, 1659 soldiers were selected by multistage sampling. Data were collected
      using the Beck Scale for Suicide Ideation (BSSI) and NEO-Five Factor Inventory.
      RESULTS: There was a significant positive correlation (r = 0.323) between
      neuroticism and suicide ideation; however, significant negative correlations
      existed between three other personality traits --extraversion [r = -0.306],
      agreeableness [r = -0.227], and conscientiousness [r = -0.271] and suicidal
      ideation. Unlike neuroticism, extraversion and conscientiousness personality
      factors could reduce significantly (as much 14% as are predicted) levels of
      suicidal ideation. CONCLUSIONS: Based on these results, neuroticism might
      increase suicide, but extraversion and conscientiousness personality traits are
      associated with a reduced risk of suicide.

PMID- 24910794
TI  - Irrigation of abdomen with imipenem solution decreases surgical site infections
      in patients with perforated appendicitis: a randomized clinical trial.
AB  - BACKGROUND: Perforated appendicitis is one of the most common causes of acute
      abdomen requiring emergent surgery for immediate appendectomy and peritoneal
      cavity irrigation; however, the efficacy of irrigation with antibiotic solutions
      is controversial. OBJECTIVES: The aim of this study was to assess the efficacy of
      imipenem solution irrigation on post-operative surgical site infections (SSIs),
      hospital length of stay, and hospital costs. We hypothesized that there would be
      lower rate of SSIs, a shorter hospital stay, and lower hospital cost in patients
      with perforated appendicitis who received peritoneal cavity irrigation with
      imipenem solution in comparison to their counterparts who received irrigation
      with normal saline. PATIENTS AND METHODS: In this randomized single-blind
      parallel-group clinical trial, we enrolled 90 patients with perforated
      appendicitis with 12-50 years of age and randomly allocated them into
      experimental group (n = 45) and control group (n = 45). The control group
      received peritoneal irrigation with normal saline (0.9%) and experimental group
      underwent peritoneal irrigation with imipenem solution (1 mg/mL). All surgical
      procedures were performed in Imam Reza Hospital of Kermanshah University of
      Medical Sciences. The study primary outcome was surgical site infections
      (including wound infection and abdominal abscess) and the secondary outcomes were
      length of hospital stay and hospital cost. Chi-squared and t-tests were used to
      analyze the study data. RESULTS: Imipenem solution irrigation was associated with
      significant clinical improvement at one-month follow-up. The experimental group
      presented with significantly lower rate of SSIs and shorter length of hospital
      stay. The experimental group had lower rate of SSIs compared to the control group
      (4.4% vs. 22.2%, respectively) (p= 0.013). The duration of hospital stay was
      nearly one day longer in control group (5.84 +/- 2.58 days) vs. experimental
      group (4.91 +/- 1.29 days) (P = 0.034), and hospital costs were $50 lower in
      experimental group ($500 +/- $292) vs. control group ($450 +/- $170) (P = 0.281).
      CONCLUSIONS: The study findings revealed that peritoneal lavage with imipenem
      solution (1 mg/mL) decreases the rate of post-operative SSIs in patients with
      perforated appendicitis in comparison to patients irrigated with normal saline
      alone. These patients also had shorter hospital stay, and lower hospital costs.

PMID- 24910795
TI  - Health information on internet: quality, importance, and popularity of persian
      health websites.
AB  - BACKGROUND: The Internet has provided great opportunities for disseminating both
      accurate and inaccurate health information. Therefore, the quality of information
      is considered as a widespread concern affecting the human life. Despite the
      increasingly substantial growth in the number of users, Persian health websites
      and the proportion of internet-using patients, little is known about the quality
      of Persian medical and health websites. OBJECTIVES: The current study aimed to
      first assess the quality, popularity and importance of websites providing Persian
      health-related information, and second to evaluate the correlation of the
      popularity and importance ranking with quality score on the Internet. MATERIALS
      AND METHODS: The sample websites were identified by entering the health-related
      keywords into four most popular search engines of Iranian users based on the
      Alexa ranking at the time of study. Each selected website was assessed using
      three qualified tools including the Bomba and Land Index, Google PageRank and the
      Alexa ranking. RESULTS: The evaluated sites characteristics (ownership structure,
      database, scope and objective) really did not have an effect on the Alexa traffic
      global rank, Alexa traffic rank in Iran, Google PageRank and Bomba total score.
      Most websites (78.9 percent, n = 56) were in the moderate category (8 <= x <=
      11.99) based on their quality levels. There was no statistically significant
      association between Google PageRank with Bomba index variables and Alexa traffic
      global rank (P > 0.05). CONCLUSIONS: The Persian health websites had better Bomba
      quality scores in availability and usability guidelines as compared to other
      guidelines. The Google PageRank did not properly reflect the real quality of
      evaluated websites and Internet users seeking online health information should
      not merely rely on it for any kind of prejudgment regarding Persian health
      websites. However, they can use Iran Alexa rank as a primary filtering tool of
      these websites. Therefore, designing search engines dedicated to explore
      accredited Persian health-related Web sites can be an effective method to access
      high-quality Persian health websites.

PMID- 24910796
TI  - Various indicators for the assessment of hospitals' performance status:
      differences and similarities.
AB  - BACKGROUND: Hospitals are the most costly operational and really important units
      of health system because they consume about 50%-89% of total health resources.
      Therefore efficient use of resources could help in saving and reallocating the
      financial and physical resources. OBJECTIVES: The aim of this study was to obtain
      an overview of hospitals' performance status by applying different techniques, to
      compare similarities and differences between these methods and suggest the most
      comprehensive and practical method of appraisal for managers and policy makers.
      PATIENTS AND METHODS: This is a cross sectional study conducted in all hospitals
      of Ahvaz (eight hospitals affiliated with Jundishapur University of Medical
      Sciences and eight non-affiliated hospitals) during 2007 to 2011. Two kinds of
      data were collected through separate special checklists. Excel 2007 and Windeap
      2.1 software were applied for data analysis. RESULTS: The present findings show
      that the average of bed occupancy rate (BOR) in the studied hospitals was about
      65.91 +/- 1.16. The maximum number of inefficient hospitals in the present study
      happened in the years 2007, 2008 and 2010 (four hospitals) but there were two
      hospitals in the third part of the present graph which had maximum level of
      efficiency and optimal level of productivity in the years 2007 and 2009. Data
      Envelopment Analysis (DEA) showed that the mean score of technical efficiency for
      the studied hospitals is 0.924 +/- 0.105 with the minimum of 0.585 +/- 0.905 for
      hospital number 1. Furthermore It shows that only five hospitals (31.25%) reach
      complete technical efficiency (TE) scores across all five years of 2007-11 (TE =
      1). CONCLUSIONS: Results of the present and similar studies should be considered
      for the future planning and resource allocation of Iranian public hospitals. At
      the same time it is very important to consider need assessment results for each
      region according to its potentials, population under the coverage and other
      geographical and cultural indices. Furthermore because of potential limitations
      of each of the above models it is highly recommended to apply different methods
      of performance evaluation to reach a complete and real status view of the
      hospitals for future planning.

PMID- 24910797
TI  - Health status, intention to seek health examination, and participation in health
      education among taxi drivers in jinan, china.
AB  - BACKGROUND: Taxi drivers are exposed to various risk factors such as work
      overload, stress, an irregular diet, and a sedentary lifestyle, which make these
      individuals vulnerable to many diseases. This study was designed to assess the
      health status of this occupational group. OBJECTIVES: The objective was to
      explore the health status, the intention to seek health examination, and
      participation in health education among taxi drivers in Jinan, China. PATIENTS
      AND METHODS: The sample-size was determined scientifically. The systematic
      sampling procedure was used for selecting the sample. Four hundred taxi drivers
      were randomly selected from several taxi companies in Jinan. In total, 396 valid
      questionnaires (from 370 males and 26 females) were returned. Health status,
      intention to seek health examination, and participation in health education were
      assessed by a self-designed questionnaire. Other personal information including
      sex, age, ethnicity, marital status, years of employment as a taxi driver,
      education level, and habits were also collected. RESULTS: This survey revealed
      that 54.8% of taxi drivers reported illness in the last two weeks and 44.7% of
      participants reported chronic diseases. The prevalence rates of hypertension,
      diabetes mellitus, gastroenteritis, arthritis, and heart disease were 18.2%,
      8.8%, 26%, 18.4%, and 4.8% of questioned taxi drivers, respectively. Significant
      self-reported symptoms included fatigue, waist and back pain, headache,
      dyspepsia, and dry throat affecting 49.7%, 26.2%, 23.5%, 26%, and 27% of
      participants, respectively. In total, 90.1% of subjects thought that it was
      necessary to receive a regular health examination. Only 17.9% of subjects had
      been given information about health education, and significantly, more than 87%
      of subjects who had been given information about health education reported that
      the information had been helpful. CONCLUSIONS: Taxi drivers' health was poor in
      our survey. Thus, using health education interventions to improve knowledge and
      change in behaviors are necessary and effective programs that improve the health
      of individuals in this special occupational group are needed.

PMID- 24910798
TI  - Psychological factors explaining the referral behavior of Iranian family
      physicians.
AB  - BACKGROUND: The recently developed policy of the family practice program in rural
      regions of Iran faced some challenges such as inefficient referral system. The
      health insurance organizations (purchaser) and health policy makers are concerned
      about the high rate of patient referrals from family physicians to specialists
      due to imposing unnecessary services and costs. OBJECTIVES: This study examined
      utility of the theory of planned behavior to explain intention of Iranian family
      physicians to reduce referral rate of patients with respiratory diseases to
      medical specialist. PATIENTS AND METHODS: An exploratory cross-sectional study,
      employing a correlational design directed by the theory of planned behavior was
      conducted. A questionnaire was developed based on an eliciting study and review
      of literature. One hundred and seventy-four family physicians working at primary
      care centers in two provinces of Iran completed the questionnaire (response rate
      of 86%). RESULTS: The finding revealed that intention of family physicians to
      reduce referral rate of patients to specialists was significantly related to two
      theory-based variables of subjective norms (r = 0.38, P < 0.001) and perceived
      behavioral control (r = 0.43, P < 0.001), and not to attitudes. A stepwise
      regression entering direct measures of the theory variables explained 35% of the
      variance on the intention, with perceived behavioral control being the strongest
      predictor. Adding background variables to the model achieved further 5% by
      variables of practice size and past referral rate behavior. CONCLUSIONS: The
      results indicated that psychological variables of the theory of planned behavior
      could explain a noticeable proportion of variance in family physician's intention
      to decrease the rate of referring patients with respiratory diseases to medical
      specialists. The intention is primarily influenced by normative and control
      considerations. These findings contribute to a better understanding of referral
      decisions by family physicians and are of great value in developing interventions
      to reduce the variation in referral rate of patients to medical specialists at
      primary care health centers.

PMID- 24910799
TI  - Challenges in evaluating clinical governance systems in iran: a qualitative
      study.
AB  - BACKGROUND: In spite of the pivotal role of clinical governance in enhancing
      quality of services provided by hospitals across the country, a scientific
      framework with specific criteria for evaluating hospitals has not been developed
      so far. OBJECTIVES: This study was conducted with the aim to identify the
      challenges involved in evaluating systems of clinical governance in Iran.
      MATERIALS AND METHODS: For the purposes of this qualitative study, 15 semi
      structured interviews with experts in the field were conducted in 2011 and the
      data were analyzed using framework analysis method. RESULTS: Five major
      challenges in evaluating clinical governance include managing human resources,
      improving clinical quality, managing development, organizing clinical governance,
      and providing patient-oriented healthcare system. CONCLUSIONS: Healthcare system
      in Iran requires a clinical governance program which has a patient-oriented
      approach in philosophy, operation, and effectiveness in order to meet the
      challenges ahead.

PMID- 24910800
TI  - Effect of Self-regulation Training on Management of Type 2 Diabetes.
AB  - BACKGROUND: Diabetes is the most common metabolic disorder which is required to
      be taken under control. According to some studies, the impact of self-regulation
      on health has been considered as a monitoring strategy to achieve individual's
      goals. OBJECTIVES: This study, which was performed in 2012, aimed at determining
      the consequences of self-regulation on controlling type 2 diabetes. PATIENTS AND
      METHODS: In this double-blind clinical trial, 60 patients with type 2 diabetes -
      who were referred to Diabetes Clinic of Bisto-Dou Bahman Hospital in Gonabad,
      Iran - were divided randomly into case and control groups. Self-regulation
      questionnaire, nutritional information and physical activity checklists were
      completed by both groups once at the beginning and once at end of the training.
      Fasting blood sugar (FBS) of both groups were measured as well. Case group was
      trained for a month, whereas the control group received no special training. Data
      were analyzed by SPSS version 19 software, K-square and paired t-tests. RESULTS:
      Comparing the case with the control group before and after the training showed
      that teaching patients self-regulatory strategies had significant impact on
      lowering blood sugar (-16.50 vs. -2.47, P < 0.001), observing dietary behaviors
      (5.97 vs. -0.87, P < 0.001) and increasing physical activities (6.2 vs. -0.73, P
      < 0.001) of the former group. CONCLUSIONS: Learning self-regulations has a role
      to play in controlling type 2 diabetes. Therefore, it is suggested to
      professionals in healthcare centers to educate patients about self-regulatory
      techniques and use them as auxiliary methods for keeping type 2 diabetes under
      control.

PMID- 24910801
TI  - Complementary treatment in chronic pelvic pain syndrome: a case report study.
AB  - INTRODUCTION: The use of traditional medicine has been emerged in the treatment
      of BPS (bladder pain syndrome) due to its high prevalence and expenses and its
      insufficient treatment by conventional therapies. Iranian traditional medicine
      has discussed such diseases. Considering the signs and symptoms of BPS and
      "reeh", the proposed mechanism of flatulency as casualty of recurrent circulating
      pains seems to be a proper diagnose. So, as a preliminary study the authors
      administered Horse Mint as one of effective traditional herbs on flatulent pain
      in a patient with BPS. CASE PRESENTATION: A 60-year-old female was referred with
      the diagnosis of BPS. Six clinical visits with 2-week intervals were performed
      for patient, and the NIH-ICSI (National Institutes of Health Interstitial
      Cystitis Symptom Index) was completed, which was used as a pretreatment symptom
      quantifier and post-treatment outcome tool. Horse mint (Mentha longifolia) was
      prescribed twice a day for 12 weeks. DISCUSSION: Clinical visits showed
      alleviation of signs, symptoms, and changes in the patient's NIH-ICSI score,
      suggesting further studies on this field.

PMID- 24910802
TI  - The PI3K/AKT Pathway and FOXO3a Transcription Factor Mediate High Glucose-Induced
      Apoptosis in Neonatal Rat Ventricular Myocytes.
AB  - BACKGROUND: PI3K/AKT pathway plays major roles in regulating cardiomyocyte
      metabolism. The roles of PI3K/AKT pathway and FOXO3a in mediating high glucose
      induced apoptosis in cardiomyocytes remain unclear. OBJECTIVES: In this
      experimental study, we investigated the mechanisms of the PI3K/AKT pathway and
      FOXO3a in mediating hyperglycemia-induced apoptosis in neonatal rat ventricular
      myocytes (NRVMs). MATERIALS AND METHODS: NRVMs were adopted as the cell model to
      investigate the roles of PI3K/AKT and FOXO3a in mediating hyperglycemia-induced
      apoptosis in cardiomyocytes. Annexin-V-FITC staining and PI staining were used to
      evaluate the apoptosis in NRVMs under indicated conditions of serum starvation,
      high glucose exposure, and pharmacological or genetic manipulations on the
      expressions of PI3K/AKT and FOXO3a. Western blotting was conducted to evaluate
      the cytoplasmic/nuclear localization of FOXO3a in NRVMs exposed to high glucose.
      FOXO3a transcriptional activity was measured by luciferase reporter assay.
      RESULTS: High glucose (30 mM) induced significant apoptosis in serum-starved
      NRVMs as compared with normal glucose (5 mM) control (12.01 +/- 0.76% vs. 2.86 +/
      0.55%; P < 0.001). Treatment with IGF1 attenuated hyperglycemia-induced
      apoptosis by 68% (3.23 +/- 0.76% vs. 9.97 +/- 1.29%; P < 0.001; n = 3) in
      comparison with the non-treated control. Treatment with PI3K inhibitor LY294002
      enhanced hyperglycemia-induced apoptosis by 109% (20.83 +/- 1.87% vs. 9.97 +/-
      1.29%; P < 0.001; n = 3) in comparison with the non-treated control. Over
      expression of AKT by transduction with CA-AKT attenuated hyperglycemia-induced
      apoptosis by 47% (5.48 +/- 0.35% vs.10.31 +/- 0.94%; P < 0.001; n = 3) in
      comparison with the empty-vector control. Transduction with DN-AKT enhanced high
      glucose-induced apoptosis by 105% (21.13 +/- 1.11% vs. 10.31 +/- 0.94%; P <
      0.001; n = 3) in comparison with the empty-vector control. Western blotting
      showed that high glucose induced a significant increase in FOXO3a nuclear
      localization. Luciferase reporter assay showed that high glucose induced a
      significant increase of 310% (P < 0.001; n = 3) in FOXO3a transcriptional
      activity against Fas ligand when NRVMs were transducted with TM-FOXO3a in
      comparison with the empty-vector control. CONCLUSIONS: The PI3K/AKT pathway
      mediated hyperglycemia-induced apoptosis of NRVMs through the translocation of
      FOXO3a to nuclei and the resultant enhanced transcriptional activity of FOXO3.

PMID- 24910803
TI  - A Comparative Serological Study of Toxoplasmosis in Pregnant Women by CLIA and
      ELISA Methods in Chalus City Iran.
AB  - BACKGROUND: Toxoplasmosis is the most common disease in humans and animals
      (zoonosis) caused by the protozoan parasite Toxoplasma gondii. The disease is
      usually appeared as asymptomatic in immunocompromised individuals but its most
      common symptom is lymphadenopathy. Shortly before or during the first trimester
      of pregnancy, this disease can be transferred to the fetus and cause serious
      infection in the fetus. In late pregnancy (third trimester), the complications of
      this infection is very low or unsigned. Due to the absence of non-specific
      clinical symptoms or slight infection in pregnant women, prenatal diagnosis is
      often impossible. OBJECTIVES: Since no research compared these two methods, we
      decided to compare these methods and determine which method works better for
      diagnosis of toxoplasmosis. PATIENTS AND METHODS: In this study, 50 pregnant
      women who referred to the Chalus Health Center laboratory were included and the
      blood samples were tested for presence of IgG and IgM antibodies of Toxoplasma
      gondii by both ELISA and Chemiluminescence methods. RESULTS: Of the 50 samples
      tested by the ELISA method, 26 samples (52%) were positive for IgG . No samples
      were positive for IgM. Of the 50 samples tested by the Chemiluminescence method,
      28 samples (56%) were positive for IgG. No samples were positive for IgM.
      CONCLUSIONS: A significant relationship between the age of the youngest child and
      the infection rate was seen. No significant correlation between age, number of
      individuals in the household, number of children, location, type of construction,
      consumption of greens, the way of greens and meat consumption, drug use, history
      of stillbirth and infection levels was seen.

PMID- 24910804
TI  - Design and construct an optical device to determine relative blood volume in
      patients undergoing hemodialysis.
AB  - BACKGROUND: Occurrence of hypotension during hemodialysis in nearly 20-30% of
      patients, shows is the necessity of continuous monitoring the patients' blood
      pressure during hemodialysis. Since directly and non-invasively continuous blood
      pressure monitoring, is not easy, finding a parameter related to blood pressure,
      for indirect monitoring is of great value. Related blood volume (RBV) is one of
      the parameters, related to blood pressure and have a good potential to reflect
      the patient's hemodynamic condition. OBJECTIVES: The main objective of this study
      was to design and construct an optical device to determine the RBV in patients
      undergoing hemodialysis, during the process. MATERIALS AND METHODS: After initial
      studies in order to select a proper sensor, using the ORCAD software, an analog
      circuit was designed. The implementation and modification of the circuit was done
      by the clinical tests, using expired blood. Afterwards, for calculation the RBV,
      controlling the display, data storage and sending it to the computer, an ATmega16
      microcontroller was used. For programing the microcontroller, CodeVision software
      and then Altium Designer software were used for the circuit compression, in order
      to design the printed circuit board. Finally, all parts of the analog and digital
      circuit, AC to DC converter and the LCD were embedded in a box. RESULTS: After
      finalization of the device and before testing it in a real situation, expired
      blood was used for final evaluation. The evaluation was done by changing the
      blood concentration, at the start point by adding water to it. In fact, the
      device can track the changes in blood concentration and display the RBV. After
      this evaluation, the device was tested in a clinical situation. The results
      showed there are no interactions between this device and the other devices used
      in the dialysis section and it can work properly in order to measure the RBV.
      CONCLUSIONS: Considering the hypotension and its consequences in a patient on
      hemodialysis, solving this problem seems necessary. One method for preventing
      this, is to use the blood pressure related parameters and one of these parameters
      is the RBV. In this study, in order to measure the RBV, a device was designed and
      evaluated by expired blood and also tested in a clinical situation. Results
      showed that the device could work properly in order to measure the RBV.

PMID- 24910805
TI  - An educational program based on the successful aging approach on health-promoting
      behaviors in the elderly: a clinical trial study.
AB  - BACKGROUND: Many criteria of successful aging are directly connected with Health
      Promoting Behaviors. OBJECTIVES: The current study aimed to evaluate the effect
      of an educational program based on the successful aging approach on health
      promoting behaviors in the elderly. PATIENTS AND METHODS: This clinical trial
      study was conducted on 464 Iranian elderly people over 60 years who were admitted
      at Health Houses for 12 months. Participants were selected through a two-stage
      cluster sampling and were placed in the control and intervention groups (232
      participants in each group). The data collection tools included: a demographic
      checklist, Palmore Facts on Aging Quiz and the second version of Health Promoting
      Lifestyle Profile. The intervention was designed based on adult strategy
      education in five 45-minute sessions. The data obtained 3 months after the
      intervention were compared with the data obtained before the intervention. The
      data were analyzed using the descriptive and analytical tests such as paired T
      test with SPSS version 20, at the statistical significant level 0.05. RESULTS:
      The mean age of the participants in this study was 65.9 +/- 3.6 (range 60-73).
      Results showed a statistically significant difference between the intervention
      and control group after the intervention in the mean scores of awareness of aging
      facts and score of health promoting behaviors. CONCLUSIONS: Focusing on
      successful aging and adopting HPBs can prevent and decrease aging problems which
      in turn decreases the financial burden and related costs. This is especially
      important for the policy and decision makers of the health systems.

PMID- 24910806
TI  - Aortic dissection and postpartum cardiomyopathy in a postpartum young woman: a
      case report study.
AB  - INTRODUCTION: Aortic dissection is a rare condition in young women and usually
      related with congenital anomalies of aorta and connective tissue disorders. We
      reported a 34-year-old postpartum woman with aortic dissection. CASE
      PRESENTATION: The patient complained of respiratory distress and weakness with no
      abdominal pain or chest pain 20 days after delivery and had no history of
      hypertension during pregnancy and perinatal or prior heart disease. Postpartum
      cardiomyopathy and left ventricular dysfunction were diagnosed by imaging study
      and cardiac enzyme level. Finally, CT-scan was performed and showed aortic
      dissection. The patient underwent surgery and after surgery, she was alive
      without any problem. CONCLUSIONS: Patients with peripartum cardiomyopathy and
      aortic dissection could be cured with good medical care.

PMID- 24910807
TI  - Cotrimoxazole - optimal dosing in the critically ill.
AB  - The optimum dosage regimen for cotrimoxazole in the treatment of life threatening
      infections due to susceptible organisms encountered in critically ill patients is
      unclear despite decades of the drug's use. Therapeutic drug monitoring to
      determine the appropriate dosing for successful infection eradication is not
      widely available. The clinician must utilize published pharmacokinetic,
      pharmacodynamic, and effective inhibitory concentration information to determine
      potential dosing regimens for individual patients when treating specific
      pathogens. Using minimum inhibitory concentrations known to successfully block
      growth for target pathogens, the pharmacokinetics of both trimethoprim and
      sulfamethoxazole can be utilized to establish empiric dosing regimens for
      critically ill patients while considering organ of clearance impairment. The
      author's recommendations for appropriate dosing regimens are forwarded based on
      these parameters. 

PMID- 24910808
TI  - Information Needs Priorities in Patients Diagnosed With Cancer: A Systematic
      Review.
AB  - Information-sharing is an integral part of cancer care. Several studies have
      examined the information needs of patients with various types of cancer. However,
      the priorities of information needs among patients with cancer have not been
      reported. A systematic review was performed to identify published studies that
      examined priorities of information needs in patients with cancer. PubMed (1966 to
      February 2012), PsycINFO (1967 to February 2012), and CINAHL (1982 to February
      2012) databases were searched to access relevant medical, psychological, and
      nursing literature. Thirty studies involving patients with breast, prostate,
      lung, colorectal, gynecologic, hematologic, and other cancers revealed patients'
      information needs priorities. The top three patient information priorities were
      related to prognosis, diagnosis, and treatment options. The top information
      priorities reported in this systematic review could serve as a start to elicit
      patients' information needs and guide patient education across the cancer care
      continuum. Being able to prioritize the most-needed information can make patient
      encounters more meaningful and useful.

PMID- 24910809
TI  - Protonation-Induced Microphase Separation in Thin Films of a Polyelectrolyte
      Hydrophilic Diblock Copolymer.
AB  - Block copolymers composed of poly(oligo ethylene glycol methyl ether
      methacrylate) and poly(2-vinylpyridine) are disordered in the neat state but can
      be induced to order by protonation of the P2VP block, demonstrating a tunable and
      responsive method for triggering assembly in thin films. Comparison of
      protonation with the addition of salts shows that microphase separation is due to
      selective protonation of the P2VP block. Increasing acid incorporation and
      increasing 2-vinylpyridine content for P2VP minority copolymers both promote
      increasingly phase-separated morphologies, consistent with protonation increasing
      the effective strength of segregation between the two blocks. The self-assembled
      nanostructures formed after casting from acidic solutions may be tuned based on
      the amount and type of acid incorporation as well as the annealing treatment
      applied after casting, where both aqueous and polar organic solvents are shown to
      be effective. Therefore, POEGMA-b-P2VP is a novel ion-containing block copolymer
      whose morphologies can be facilely tuned during casting and processing by
      controlling its exposure to acid.

PMID- 24910810
TI  - Nutrigenomics and Cancer Prevention.
AB  - Mounting evidence continues to point to dietary habits as a modifier of cancer
      risk and tumor behavior; although it is clear that considerable variability
      occurs across studies. While genetic public health messages can be developed, the
      use of mean values may result in underexposure to some essential and nonessential
      food components, yet precipitate overexposure to nutrients. Undeniably,
      inconsistencies in the literature may reflect variation in timing of exposures to
      specific dietary constituents, interactions with the food matrix, processing
      technologies, or the genomic variation among individuals, which can influence
      absorption, metabolism, and/or the molecular target. Inter-individual variability
      in genetics, epigenetics, transcriptomics, proteomics, metabolomics, or
      microbiomics can influence the magnitude and direction of response to bioactive
      food components, as briefly reviewed in this article. Unquestionably,
      understanding nutrigenomics holds promise to reveal those who will benefit most
      from dietary interventions plus identify any who might be placed at risk due to
      overexposures.

PMID- 24910811
TI  - Circulating MicroRNAs in gynecological malignancies: from detection to
      prediction.
AB  - MicroRNAs (miRNAs) have been demonstrated to play critical roles in many
      physiological and pathophysiological processes. The presence of altered miRNA
      profiles in human body fluids has been reported for a number of diseases
      including gynecological malignancies. In this review, we summarized the current
      progresses of circulating miRNAs associated with malignancies in gynecology, with
      an emphasizing on the circulating miRNAs as diagnostic and prognostic biomarkers
      in ovarian cancer, endometrial carcinoma and cervical cancer. 

PMID- 24910812
TI  - MRI findings in Post-operative Bilateral Posterior Ischemic Optic Neuropathy.

PMID- 24910813
TI  - Sparse Representation for Prediction of HIV-1 Protease Drug Resistance.
AB  - HIV rapidly evolves drug resistance in response to antiviral drugs used in AIDS
      therapy. Estimating the specific resistance of a given strain of HIV to
      individual drugs from sequence data has important benefits for both the therapy
      of individual patients and the development of novel drugs. We have developed an
      accurate classification method based on the sparse representation theory, and
      demonstrate that this method is highly effective with HIV-1 protease. The
      protease structure is represented using our newly proposed encoding method based
      on Delaunay triangulation, and combined with the mutated amino acid sequences of
      known drug-resistant strains to train a machine-learning algorithm both for
      classification and regression of drug-resistant mutations. An overall cross
      validated classification accuracy of 97% is obtained when trained on a publically
      available data base of approximately 1.5*104 known sequences (Stanford HIV
      database http://hivdb.stanford.edu/cgi-bin/GenoPhenoDS.cgi). Resistance to four
      FDA approved drugs is computed and comparisons with other algorithms demonstrate
      that our method shows significant improvements in classification accuracy.

PMID- 24910814
TI  - Plastic Surgeon Expertise in Predicting Breast Reconstruction Outcomes for
      Patient Decision Analysis.
AB  - BACKGROUND: Decision analysis offers a framework that may help breast cancer
      patients make good breast reconstruction decisions. A requirement for this type
      of analysis is information about the possibility of outcomes occurring in the
      form of probabilities. The purpose of this study was to determine if plastic
      surgeons are good sources of probability information, both individually and as a
      group, when data are limited. METHODS: Seven plastic surgeons were provided with
      pertinent medical information and preoperative photographs of patients, and were
      asked to assign probabilities to predict number of revisions, complications, and
      final aesthetic outcome using a questionnaire designed for the study. Logarithmic
      strictly proper scoring was used to evaluate the surgeons' abilities to predict
      breast reconstruction outcomes. Surgeons' responses were analyzed for calibration
      and confidence in their answers. RESULTS: As individuals, there was variation in
      surgeons' ability to predict outcomes. For each prediction category, a different
      surgeon was more accurate. As a group, surgeons possessed knowledge of future
      events despite not being well calibrated in their probability assessments.
      Prediction accuracy for the group was up to six-fold greater than that of the
      best individual. CONCLUSIONS: The use of individual plastic surgeon-elicited
      probability information is not encouraged unless the individual's prediction
      skill has been evaluated. In the absence of this information, a group consensus
      on the probability of outcomes is preferred. Without a large evidence base for
      calculating probabilities, estimates assessed from a group of plastic surgeons
      may be acceptable for purposes of breast reconstruction decision analysis.

PMID- 24910815
TI  - Anesthetic management for lower limb fracture in severe aortic valve stenosis and
      fat embolism: a case report and review of literature.
AB  - INTRODUCTION: Anesthesia in severe aortic stenosis, which describes a valve
      surface area less than 1 cm(2), can result in rapid clinical deterioration and
      patient mortality. These patients may require treatment for aortic stenosis
      before any surgical intervention. In suitable patients percutaneous balloon
      aortic valvutomy appears to carry lower risk, but in emergency situations, it is
      important to determine which kind of anesthesia technique has the lowest risk for
      these patients, without any cardiac intervention. CASE PRESENTATION: In this case
      report, we present a patient who had tibia and fibula fractures and a symptomatic
      severe critical aortic stenosis which was diagnosed during a preoperative visit.
      The patient had exertional dyspnea, palpitations and fainting history, but he had
      not received any medical therapy before the present admission. During
      hospitalization and preoperative evaluation, a fat embolism occurred and the
      patient was admitted to the intensive care unit. Immediately after his recovery,
      we successfully managed the tibia and fibula fracture fixation without any
      cardiac intervention. CONCLUSIONS: Our anesthesia method was sciatic and femoral
      nerve block under double ultrasonic and nerve stimulator guidance.

PMID- 24910817
TI  - Renaming gestational diabetes mellitus: A psychosocial argument.

PMID- 24910816
TI  - Propofol and alfentanil in treatment of a patient with episodic cluster headache.
AB  - INTRODUCTION: Cluster headache is a severe hemifacial pain with concomitant
      symptoms such as lacrimation, conjunctival congestion, and nasal discharge.
      Peripheral (to be a spectrum of trigeminal autonomic cephalgia) and central
      (hypothalamus) disorders have been suggested to be involved. Several modalities
      have been recommended to prevent or alleviate this devastating headache. CASE
      PRESENTATION: In this case report, we presented a young man with an acute cluster
      headache who responded dramatically to the treatment with propofol and
      alfentanil. CONCLUSIONS: Propofol and alfentanil combination can be considered as
      a treatment approach in the attack phase of cluster headache.

PMID- 24910818
TI  - Diabetes therapy by the ear.

PMID- 24910819
TI  - Training in endocrinology: The Indian perspective.

PMID- 24910820
TI  - Online risk engines and scoring tools in endocrinology.
AB  - With evolution of evidence-based medicine, risk prediction equations have been
      formulated and validated. Such risk engines and scoring systems are able to
      predict disease outcome and risks of possible complications with varying degrees
      of accuracy. From health policy makers point of view it helps in appropriate
      disbursement of available resources for greatest benefit of population at risk.
      Understandably, the accuracy of prediction of different risk engines and scoring
      systems are highly variable and has several limitations. Each risk engine or
      clinical scoring tool is derived from data obtained from a particular population
      and its results are not generalizable and hence its ability to predict
      risk/outcome in a different population with differences in ethnicity, ages, and
      differences in distribution of risk factors over time both within and between
      populations. These scoring systems and risk engines to begin with were available
      for manual calculations and references/use of formula and paper charts were
      essential. However, with evolution of information technology such calculations
      became easier to make with use of online web-based tools. In recent times with
      advancement of android technology, easy to download apps (applications) has
      helped further to have the benefits of these online risk engines and scoring
      systems at our finger tips. 

PMID- 24910821
TI  - Pituitary dysfunction in infective brain diseases.
AB  - Infectious diseases of the central nervous system (CNS) are increasingly being
      recognized as important causes of hypopituitarism. Although tuberculosis is the
      most common agent involved, non-mycobacterial agents like viruses, bacteria,
      fungus, and protozoa are important causes in our country. Involvement post
      infections could be due to a strategically located tuberculoma, or pituitary
      abscess, or meningoencephalitis. Although it might not be reasonable to screen
      all patients with CNS infections for hypopituitarism, awareness of the
      possibility and clinical follow-up for suggestive symptoms is required. 

PMID- 24910822
TI  - Management issues with exogenous steroid therapy.
AB  - Glucocorticoids (GCs) are extensively used for various inflammatory and
      autoimmune disorders, but long term use of these agents is not without
      complications. Almost every GC formulations (e.g. oral, topical, inhaled, etc.)
      can cause systemic side effects. It can range from minor side effects (e.g.
      weight gain) to life-threatening effects (e.g. adrenal suppression, sepsis,
      etc.), which may require immediate intervention. Therefore, the decision to
      institute steroid therapy always requires careful consideration of the relative
      risk and benefit in each patient. The objectives of this study are to discuss
      monitoring of patients on GCs and management of the complications of GCs. 

PMID- 24910823
TI  - Calcium and vitamin D in post menopausal women.
AB  - Calcium and Vitamin D are widely used therapies for Osteoporosis. Vitamin D is
      not a vitamin in true sense since it is produced in response to the action of
      sunlight on skin. Vitamin D has multiple roles in the body, not all of them well
      understood. Vitamin D supplementation must be considered a form of hormone
      replacement therapy. Therefore it raises all the questions about efficacy, dose,
      and side effects. The Efficacy of use of Calcium and Vitamin D in all post
      menopausal women in terms of the prevention of fracture is uncertain. The Annual
      worldwide sales of these supplements have been several billion dollars. The
      variation of the results from various studies of Calcium and Vitamin D
      supplementation in elderly women suggest that benefit of calcium plus vitamin D
      on bone mineral density or the risk of fracture is small and may vary from group
      to group and baseline Vitamin D status. Women taking supplemental vitamin D and
      calcium have a statistically increased incidence of renal stones, according to
      evidence from the Women's Health Initiative. Studies have shown association
      between calcium use and increased risk for cardiovascular disease. In a recent
      review of evidence from 6 randomized trials evaluating the use of vitamin D and
      calcium to prevent fractures in postmenopausal women who are not living in a
      nursing home or other institution, the United States Preventive Task Force
      (USPTF) found no evidence of a benefit from supplementation with 400 IU or less
      of vitamin D3 and 1000 mg or less of calcium. Also in a report from institute of
      Medicine Committee, there was insufficient evidence, particularly from randomized
      trials, that vitamin D treatment affected the risk of non skeletal outcomes like
      risk of cancer, cardiovascular disease, diabetes, infections, autoimmune disease,
      and other extra skeletal outcomes. 

PMID- 24910824
TI  - Andropause: Current concepts.
AB  - Andropause or late-onset hypogonadism is a common disorder which increases in
      prevalence with advancing age. Diagnosis of late-onset of hypogonadism is based
      on presence of symptoms suggestive of testosterone deficiency - prominent among
      them are sexual symptoms like loss of libido, morning penile erection and
      erectile dysfunction; and demonstration of low testosterone levels. Adequate
      therapeutic modalities are currently available, but disparate results of clinical
      trial suggest further evaluation of complex interaction between androgen
      deficiency and ageing. Before initiating therapy benefits and risk should be
      discussed with patients and in case of poor response, alternative cause should be
      investigated. 

PMID- 24910825
TI  - In-patient management of diabetes: Controversies and guidelines.
AB  - Hyperglycemia is associated with adverse outcomes in hospitalized patients with
      and without previously known diabetes. Some therapies that are used in the in
      patient setting, including glucocorticoids, enteral and parenteral nutrition are
      associated with new onset hyperglycemia even in previously normoglycemic
      patients. Current guidelines advise that fasting and premeal blood glucose (BG)
      be maintained at < 140 mg/dl, with maximal random BG < 180 mg/dl in non
      critically ill-patients. In critically ill-patients, intravenous (IV) insulin
      infusion therapy with BG targets of 140-180 effectively maintains glycemic
      control with a low risk for hypoglycemia. Protocols targeting "tight" glycemic
      control, defined as BG 80-110 mg/dl, are no longer recommended due to the high
      frequency of severe hypoglycemia. Rational use of basal bolus insulin (BBI)
      regimens in non-critical care and IV insulin infusions in critical care settings
      has been demonstrated to effectively achieve and maintain recommended BG targets
      with low risk for hypoglycemia. The safety of BBI relies upon provider awareness
      of prescribing recommendations for initiating and adjusting insulin regimens
      according to changes in overall clinical and nutritional status, as well as
      careful review of daily BG measurements. Smooth transition of care to the out
      patient setting is facilitated by providing oral and written instructions
      regarding the timing and dosing of insulin as well as education in basic skills
      for home management. 

PMID- 24910826
TI  - Subclinical hypothyroidism: Controversies to consensus.
AB  - Diagnoses of subclinicaal hypothyroidism (SCH) is biochemically made, when serum
      thyroid stimulating hormone (TSH) levels is elevated while free thyroid hormone
      levels are within normal reference range. SCH is diagnosed after excluding all
      other causes of elevated TSH levels. Symptoms of SCH may vary from being
      asymptomatic to having mild nonspecific symptoms. The risk of progression to
      overt hypothyroidism is related to number of factors including initial serum TSH
      concentration, presence of auto antibodies, family history and presence goiter.
      Various screening recommendations for thyroid function assessment are in
      practice. There are still controversies surrounding SCH and associated risk of
      various cardiovascular diseases (CVDs), pregnancy outcomes, neuropsychiatric
      issues, metabolic syndrome, and dyslipidemia. Consensus will require more large
      randomized clinical studies involving various age groups and medical condition,
      especially in developing countries. All these efforts will definitely improve our
      understanding of disease and ultimately patient outcomes. 

PMID- 24910827
TI  - Current concepts in blood glucose monitoring.
AB  - Blood glucose monitoring has evolved over the last century. The concept of
      adequate glycemic control and minimum glycemic variability requires an ideal,
      accurate and reliable glucose monitoring system. The search for an ideal blood
      glucose monitoring system still continues. This review explains the various blood
      glucose monitoring systems with special focus on the monitoring systems like self
      monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS).
      It also focuses on the newer concepts of blood glucose monitoring and their
      incorporation in routine clinical management of diabetes mellitus. 

PMID- 24910828
TI  - Lessons from the look action for health in diabetes study.
AB  - The Look Action for Health in Diabetes AHEAD Study was designed as a long-term
      randomized controlled clinical trial and powered to detect differences in
      cardiovascular outcomes, the primary cause of early morbidity and mortality in
      type 2 diabetes, among subjects randomized to receive an intensive lifestyle
      intervention or a control group of diabetes support and education. The study was
      terminated early due to the absence of any difference in the primary outcome,
      defined as a composite of the first postrandomization occurrence of fatal and
      nonfatal myocardial infarction and stroke, or angina requiring hospitalization.
      However, important secondary favorable outcomes were observed in those receiving
      the intensive lifestyle intervention. This included more weight loss, greater
      fitness, less disability, less depression, reductions in sleep apnea and urinary
      incontinence, better glycemic control, and more subjects experiencing diabetes
      remission. These results underscore the importance of lifestyle interventions as
      a component of diabetes therapy. Long-term follow-up of Look AHEAD participants
      is planned, despite discontinuation of the intensive lifestyle program. 

PMID- 24910829
TI  - Lithium toxicity and myxedema crisis in an elderly patient.
AB  - While thyroid dysfunction is a frequent complication of lithium treatment,
      myxedema crisis is a rare occurrence with a handful of cases described. Here, we
      describe a patient receiving lithium for about a decade for bipolar disorder, who
      presented with myxedema crisis and lithium toxicity. In this patient, myxedema
      crisis was likely precipitated by lithium toxicity and community acquired
      pneumonia. The effects of lithium on thyroid are briefly reviewed. OBJECTIVE: To
      describe an elderly male who was diagnosed with myxedema crisis and lithium
      toxicity. CASE REPORT: A 70-year-old male was admitted in our hospital with
      history of gradual onset progressive decrease in level of consciousness and
      altered behavior for last 1 month. Patient also had history of respiratory tract
      symptoms for 1 week. Patient was a known case of diabetes and bipolar affective
      disorder for which he had been receiving insulin and lithium for 10 years. One
      year earlier, patient was admitted in our ward for glycemic control and
      evaluation of complications and was found to be clinically and biochemically
      euthyroid; he never returned for follow up until the present admission. On
      examination patient had incoherent speech, hypothermia, and bradycardia. Thyroid
      function showed thyroid-stimulating hormone >150 IU/ml, Tetraiodothyronine (T4)
      <1 MUg/dl, anti-thyroid peroxidase titer of 60 IU/ml. The serum lithium level was
      2.9 nmol/L (therapeutic level 0.2-1.2 nmol/L). He was managed with levothyroxine,
      starting with a loading oral dose of 500 MUg through ryles tube followed by 100
      MUg daily, IV antibiotics and fluids; lithium was stopped after consultation with
      a psychiatrist. From day 5, patient started showing progressive improvement and
      by day 10, he had a Glasgow Coma Scale of 15/15, normal electrolyte, serum
      creatinine of 1.8 mg/dl and serum lithium level of 0.5 nmol/L. CONCLUSION:
      Lithium-induced hypothyroidism may be life-threatening, thyroid function should
      be monitored before and during lithium therapy and drug should be discontinued
      and appropriate therapy instituted if hypothyroidism develops.

PMID- 24910830
TI  - Thyroid associated orbitopathy with ocular myasthenia in primary hypothyroidism:
      Keep those eyes open.
AB  - Thyroid associated orbitopathy, although seen most commonly with thyrotoxicosis,
      is also known to occur in primary hypothyroidism. Myasthenia gravis is an
      autoimmune condition with an established association with autoimmune thyroid
      disease. We report the case of a patient who presented with recent onset
      unilateral ptosis that was fatigable with a history of proptosis since a year. On
      examination, she had a goiter, bilateral proptosis, restriction of upward gaze
      and adduction both eyes and normal pupils. Investigations revealed primary
      hypothyroidism with anti-thyroid peroxidase positive and anti-acetylcholine
      receptor antibody positive. Computerized tomography orbit showed thickening of
      medial and inferior rectus characteristic of thyroid orbitopathy. A diagnosis of
      primary hypothyroidism with thyroid orbitopathy with ocular myasthenia gravis was
      made. Patient is on Levothyroxine and anticholinesterase medications and is on
      follow-up. We present this case to highlight that the presence of ptosis in a
      patient with thyroid orbitopathy should alert the clinician to the possible
      coexistence of myasthenia gravis. 

PMID- 24910831
TI  - A swinging heart.
AB  - We present a case of young female presenting with clinical features of cardiac
      tamponade. On initial investigation, the etiology of cardiac tamponade could not
      be made. The presence of bradycardia with cardiac tamponade prompted us to
      perform thyroid function test which lead to the diagnosis of hypothyroidism. 

PMID- 24910832
TI  - Bilateral thecoma presenting as premenopausal hirsutism: Laproscopic removal.
AB  - Hyperandrogenism is a common disorder among women in the reproductive age group.
      One of the rare causes for androgen excess is sex cord- stromal tumors of the
      ovary. These are usually unilateral. Here we report case of a 48 year old woman
      who presented with hyperandrogenism due to bilateral ovarian thecoma. Androgen
      levels normalized following resection of the tumor. This, to the best of our
      knowledge, is the first case of bilateral thecoma presenting as hirsutism in a
      premenopausal woman. 

PMID- 24910833
TI  - Seizure as a presenting manifestation of vitamin D dependent rickets type 1.
AB  - There are two types of vitamin D dependent rickets (VDDR) that cause rickets in
      children. VDDR type 1 (VDDR-I) is caused by an inborn error of vitamin D
      metabolism, which interferes with renal conversion of calcidiol (25OHD) to
      calcitriol (1,25(OH)2D) by the enzyme 1-alpha-hydroxylase. Patients with VDDR-I
      have mutations of chromosome 12 that affect the gene for the enzyme 1-alpha
      hydroxylase, resulting in decreased levels of 1,25(OH) vitamin D. Clinical
      features include growth failure, hypotonia, weakness, rachitic rosary,
      convulsions, tetany, open fontanels and pathologic fractures. We report a case of
      VDDR-I in 14-month-old male child. Establishing an early diagnosis of these
      genetic forms of rickets is challenging, especially in developing countries where
      nutritional rickets is the most common variety of the disease where genetic
      diagnosis is not always possible because of financial constraints. A prompt
      diagnosis is necessary to initiate adequate treatment, resolve biochemical
      features and prevent complications, such as severe deformities that may require
      surgical intervention. 

PMID- 24910834
TI  - Diabetic muscle infarction: An unrecognised complication of diabetes - A case
      report from subhimalayan region of India.
AB  - A case of acute onset unilateral painful swelling of thigh is being presented
      where a high index of suspicion based on clinical presentation and characteristic
      MRI findings establish the diagnosis of DMI and avoided an inappropriate
      diagnosis and treatment. 

PMID- 24910835
TI  - Vitamin D status of patients with type 2 diabetes and sputum positive pulmonary
      tuberculosis.
AB  - INTRODUCTION: Vitamin D deficiency is expected to be higher in patients with
      diabetes and pulmonary tuberculosis (TB). Studies estimating prevalence in the
      subset of patients with both diabetes and pulmonary TB are scarce. MATERIALS AND
      METHODS: A total of 155 subjects were recruited; 46 patients with type 2
      diabetes, 39 non-diabetic healthy controls, 30 patients of pulmonary TB and 40
      patients with both pulmonary TB and type 2 diabetes. Vitamin D level (25 OH
      vitamin D) levels were done for all the 4 groups. RESULTS: Mean vitamin D levels
      were not different between groups with TB, diabetes mellitus or combination of
      both, but the prevalence of severe vitamin D deficiency was higher in the group
      with both diabetes and TB (45%) as compared with the group with only TB (26.66%)
      and diabetes (17.39%) and healthy controls (7.69%). CONCLUSION: The prevalence of
      patients with severe vitamin D deficiency is higher in patients with dual
      affection of TB and diabetes mellitus as compared with either disorder alone
      implying that patients with type 2 diabetes with the most severe vitamin D
      deficiency are the one of the most predisposed to pulmonary TB.

PMID- 24910836
TI  - Acarbose improves glycemic control as add-on or monotherapy in Indian type-2
      diabetes: Findings from the GlucoVIP multinational observational study.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of the anti-diabetic
      agent acarbose (Glucobay((r))) as add-on or monotherapy in a range of patients
      with type-2 diabetes mellitus (T2DM), including those with cardiovascular
      morbidities in India. MATERIALS AND METHODS: This was a part of a prospective,
      non-interventional, non-controlled, multicentre, multinational, observational
      study. The study included patients of either gender if they were aged at least 18
      years and had untreated or pre-treated type-2 diabetes mellitus (T2DM) or
      impaired glucose tolerance and no acarbose treatment within the 3 months before
      study inclusion. RESULTS: In total, 1996 Indian patients were included in the
      effectiveness and 2010 in the safety analysis. Patients received acarbose (25-150
      mg/day). The mean age of the patients was 50.1 years and the mean BMI was 27.2
      kg/m(2). Mean 2-h post-prandial plasma glucose (PPG) value and fasting blood
      glucose (FBG) decreased from 243.9 to 169.5 mg/dl and 158.3 to 120.4 mg/dl,
      respectively after the last follow-up of 12.4 weeks. The mean HbA1c value at
      initial visit was 8.4% and was 7.4% at the last follow-up visit. FBG, PPG and
      HbA1c deceased in 90.6%, 94.4% and 52.4% patients respectively, by the last
      follow-up visit. The mean decrease in weight and waist circumference was 1.4 kg
      and 1.6 cm, respectively by the last follow-up visit. Physicians assessed the
      efficacy of drug as positive response in "very good to good" in 91.08%,
      "sufficient" in 7.92% and "insufficient" in 0.90% of patients. Also, continuation
      of Acarbose was reported in 97.09% of patients. Adverse events were reported in
      2.74% and drug-related adverse events were reported in 2.19% of patients.
      Majority of them were gastrointestinal adverse events but were not serious.
      CONCLUSION: Acarbose is effective and safe in Indian patients with T2DM. Further,
      it helps in weight reduction and has very good compliance in patients with T2DM.

PMID- 24910837
TI  - An obese young man with uncontrolled diabetes and insatiable hunger: Prader-Willi
      syndrome.
AB  - Prader-Willi syndrome (PWS) is a rare cause of obesity. With the rising incidence
      of obesity, clinicians need to be aware of genetic causes of obesity and when to
      suspect them. A case of PWS, which was diagnosed in adulthood, has been
      discussed. This case is special because of lack of history of floppiness in
      infancy and predominance behavioral problems. 

PMID- 24910838
TI  - Unusual presentation of Klinefelter syndrome.
AB  - INTRODUCTION: Klinefelter syndrome usually presents in the puberty and adulthood
      with its characteristic features. We report a boy who had Klinefelter syndrome
      with hypospadias and hydrocele. CASE NOTE: Six and half year old boy had
      complaints of genitourinary problem in the form of hypospadias, small phallus and
      hydrocele. Karyotyping showed 47,XXY. CONCLUSION: This case illustrates that
      Klinefelter syndrome was presented in the infancy with hypospadias and hydrocele
      which are very uncommon presentation of the disease.

PMID- 24910839
TI  - Seedless orchids: Issues in the anorchid adult.
AB  - Disorders of sexual differentiation (DSD) are among the challenging problems in
      the field of endocrinology. When presenting late in an adult the therapeutic as
      well as diagnostic issues may be different and difficult. Bilateral anorchia is
      rare. The desire of future parenting is a real challenge when such patients ask
      for their own biological generations. This case depicts the late presentation of
      DSD in an anorchid adult and the management issues. 

PMID- 24910840
TI  - Comparison of glucometers used in hospitals and in outpatient settings with the
      laboratory reference method in a tertiary care hospital in Mumbai.
AB  - BACKGROUND: Glucometers allow self-monitoring of blood glucose in a convenient
      manner. With the availability of various glucometers, there is a persistent
      attempt to improve the accuracy and the precision of these glucometer readings,
      so as to match the laboratory values of blood glucose. OBJECTIVE: We compared the
      glucometers used in hospital and out-patient settings with the laboratory
      reference method. MATERIALS AND METHODS: We analyzed a total of 105 blood samples
      collected from in-patient and out-patient from our tertiary care hospital. Venous
      blood samples were collected and checked on six glucometers and the same blood
      sample was sent to the laboratory for glucose estimation. The laboratory value
      was used as a reference for comparison. The accuracy was evaluated by the ISO
      criteria. The results were evaluated by Bland Altman graphs, correlation
      coefficients, scatter plots and Clarke's error grid analysis. RESULTS: We
      observed good correlation between bed side glucometer and laboratory automated
      analyzer. Among the in-patient glucometers Breeze 2, Performa and SureStep, the
      correlation coefficient was 0.97, 0.96 and 0.88 respectively. Among the
      outpatient glucometers One touch ultra 2, Active and Contour, the correlation
      coefficient was 0.97, 0.97 and 0.95 respectively. CONCLUSIONS: There is a good
      correlation between different glucometers and laboratory values especially in the
      out-patient settings. Among all in-patient glucometers, SureStep by Johnson and
      Johnson had least correlation coefficient, whereas all three out-patient
      glucometers correlated well with the laboratory values.

PMID- 24910841
TI  - Vanishing tan and unfaithfulness.
AB  - Adrenal tuberculosis is a rare manifestation of active tuberculosis and is a
      difficult diagnosis to make if its presentation is sole manifestation of
      tuberculosis. We present an interesting case of a young male who presented only
      with symptoms of hyper pigmentation and was diagnosed as adrenal tuberculosis.
      Also, this report highlights the importance of drug interaction between
      antitubercular drug and steroid which lead to the deterioration in the early part
      of treatment and, later on was corrected by increasing the dose of steroids. 

PMID- 24910842
TI  - Recovery of prolactin function following spontaneous pregnancy in a woman with
      Sheehan's syndrome.
AB  - Sheehan's syndrome (SS) presents with hypopituitarism after parturition, usually
      preceded by postpartum hemorrhage. The first symptom of the disorder is lactation
      failure because of lactotroph cell necrosis. Recovery of lactotroph function
      after initial insult has not been reported in the literature. We describe the
      evaluation of a case of SS in whom lactotroph function recovered after the second
      pregnancy. A young woman delivered her first child at the age of 25 years;
      delivery was followed by severe postpartum hemorrhage and required blood
      transfusion. Sheehan's syndrome was diagnosed because of lactotroph,
      corticotroph, thyrotroph and somatotroph failure and empty sella on MRI. She
      conceived twice spontaneously and had normal lactation after the second delivery;
      investigations confirmed the normal basal and stimulable prolactin levels. We
      presume that recovery of lactotroph function after the second pregnancy in a
      patient with SS is possibly because of stimulatory effect of estrogen and
      progesterone on residual lactotroph cells. 

PMID- 24910843
TI  - Reversible adrenal insufficiency and heterophile antibodies in a case of
      autoimmune polyendocrinopathy syndrome.
AB  - A 27-year-old male was admitted with diabetic ketoacidosis and altered sensorium
      with slurring of speech and ataxia. He was managed with intravenous insulin and
      fluids and later shifted to basal bolus insulin regimen and during further
      evaluation was diagnosed to be suffering from primary hypothyroidism and adrenal
      insufficiency. He was started on thyroxin replacement and steroids only during
      stress. After three months of follow up he was clinically euthyroid. His glycemic
      control was adequate on oral anti-hyperglycemic drugs and adrenal insufficiency
      recovered. However, his thyrotropin levels were persistently elevated on adequate
      replacement doses of thyroxin. His repeat TSH was estimated after precipitating
      serum with polyethylene glycol which revealed normal TSH. Here we report
      reversible adrenal insufficiency with hypothyroidism with falsely raised TSH
      because of presence of heterophile antibodies in a case of poly glandular
      endocrinopathy syndrome. 

PMID- 24910844
TI  - Pituitary calcification masquerading as pituitary apoplexy.
AB  - Pituitary calcification occurs commonly in lactotroph or somatotroph adenoma but
      rare in chomophobe or gonadotroph adenoma. On imaging, it can mimic hemorrhage,
      hence may masquerade pituitary apoplexy if patient present with neurological
      manifestations. We present a case of pituitary calcification which mimicked
      pituitary apoplexy. 

PMID- 24910847
TI  - Mesenchymal Stromal Cell Dependent Regression of Pulmonary Metastasis from
      Ewing's.
AB  - INTRODUCTION: Ewing's sarcoma (ES) is the second most common bone tumor in
      children. Survival has not improved over the last decade and once pulmonary
      metastatic disease is present, survival is dismal. Mesenchymal stromal cell (MSC)
      therapy has shown potential benefit for Kaposi's sarcoma; however, the role of
      progenitor cell therapies for cancer remains controversial. MSC treatment of ES
      or pulmonary metastatic disease has not been demonstrated. We have developed an
      orthotopic xenograft model of ES in which animals develop spontaneous pulmonary
      metastases. Within this model, we demonstrate the use of MSCs to target ES lung
      metastasis. MATERIALS AND METHODS: Human ES cells were transfected with
      luciferase and injected into the rib of nude mice. Development of pulmonary
      metastases was confirmed by imaging. After flow cytometry based characterization,
      MSCs were injected into the tail vein of nude mice with established local ES
      tumor or pulmonary metastasis. Mice were treated with intravenous MSCs weekly
      followed by bioluminescent imaging. RESULTS: The intravenous injection of MSCs in
      an ES model decreases the volume of pulmonary metastatic lesions; however, no
      effect on primary chest wall tumor size is observed. Thus verifying the MSC
      preferential homing to the lung. MSCs are found to "home to" the pulmonary
      parenchyma and remain engrafted up to 5 days after delivery. DISCUSSION: MSC
      treatment of ES slows growth of pulmonary metastasis. MSCs have more affinity for
      pulmonary metastasis and can effect a greater decrease in tumor growth in the
      lungs compared to the primary tumor site.

PMID- 24910845
TI  - Depolarization Controls TRAIL-Sensitization and Tumor-Selective Killing of Cancer
      Cells: Crosstalk with ROS.
AB  - Conventional genotoxic anti-cancer drugs target the proliferative advantage of
      tumor cells over normal cells. This kind of approach lacks the selectivity of
      treatment to cancer cells, because most of the targeted pathways are essential
      for the survival of normal cells. As a result, traditional cancer treatments are
      often limited by undesirable damage to normal cells (side-effects). Ideal anti
      cancer drugs are expected to be highly effective against malignant tumor cells
      with minimal cytotoxicity toward normal cells. Such selective killing can be
      achieved by targeting pathways essential for the survival of cancer cells, but
      not normal cells. As cancer cells are characterized by their resistance to
      apoptosis, selective apoptosis induction is a promising approach for selective
      killing of cancer cells. Tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) is a promising tumor-selective anti-cancer drug. However, the congenital
      and acquired resistance of some cancer cell types, including malignant melanoma
      cells, currently impedes effective TRAIL therapy, and an innovative approach that
      can override TRAIL resistance is urgently required. Apoptosis is characterized by
      cell shrinkage caused by disruption of the maintenance of the normal
      physiological concentrations of K(+) and Na(+) and intracellular ion homeostasis.
      The disrupted ion homeostasis leads to depolarization and apoptosis. Recent
      evidence suggests that depolarization is an early and prerequisite event during
      TRAIL-induced apoptosis. Moreover, diverse natural products and synthetic
      chemicals capable of depolarizing the cell membrane exhibit tumor-selective
      killing and TRAIL-sensitizing effects. Here, we discuss the role of
      depolarization in selective killing of cancer cells in connection with the
      emerging concept that oxidative stress is a critical mediator of mitochondrial
      and endoplasmic reticulum dysfunctions and serves as a tumor-selective target in
      cancer treatment. 

PMID- 24910846
TI  - The pathophysiology of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal
      eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication
      and is managed by allergen elimination and anti-allergy therapy. Although the
      pathophysiology of EoE is currently unsubstantiated, evidence implicates food and
      aeroallergen hypersensitivity in genetically predisposed individuals as
      contributory factors. Genome-wide expression analyses have isolated a remarkably
      conserved gene-expression profile irrespective of age and gender, suggesting a
      genetic contribution. EoE has characteristics of mainly TH2 type immune responses
      but also some TH1 cytokines, which appear to strongly contribute to tissue
      fibrosis, with esophageal epithelial cells providing a hospitable environment for
      this inflammatory process. Eosinophil-degranulation products appear to play a
      central role in tissue remodeling in EoE. This remodeling and dysregulation
      predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have
      an effect on enteric nerves and may also act in concert with transforming growth
      factor-beta to interfere with esophageal musculature. Additionally, the
      esophageal epithelium may facilitate the inflammatory process under pathogenic
      contexts such as in EoE. This article aims to discuss the contributory factors in
      the pathophysiology of EoE. 

PMID- 24910848
TI  - Proposal for describing procedures to correct varicocele. A new terminology.

PMID- 24910849
TI  - Terror attacks increase the risk of vascular injuries.
AB  - OBJECTIVES: Extensive literature exists about military trauma as opposed to the
      very limited literature regarding terror-related civilian trauma. However, terror
      related vascular trauma (VT), as a unique type of injury, is yet to be addressed.
      METHODS: A retrospective analysis of the Israeli National Trauma Registry was
      performed. All patients in the registry from 09/2000 to 12/2005 were included.
      The subgroup of patients with documented VT (N = 1,545) was analyzed and further
      subdivided into those suffering from terror-related vascular trauma (TVT) and non
      terror-related vascular trauma (NTVT). Both groups were analyzed according to
      mechanism of trauma, type and severity of injury and treatment. RESULTS: Out of
      2,446 terror-related trauma admissions, 243 sustained TVT (9.9%) compared to 1302
      VT patients from non-terror trauma (1.1%). TVT injuries tend to be more complex
      and most patients were operated on. Intensive care unit admissions and hospital
      length of stay was higher in the TVT group. Penetrating trauma was the prominent
      cause of injury among the TVT group. TVT group had a higher proportion of
      patients with severe injuries (ISS >= 16) and mortality. Thorax injuries were
      more frequent in the TVT group. Extremity injuries were the most prevalent
      vascular injuries in both groups; however NTVT group had more upper extremity
      injuries, while the TVT group had significantly much lower extremity injuries.
      CONCLUSION: Vascular injuries are remarkably more common among terror attack
      victims than among non-terror trauma victims and the injuries of terror
      casualties tend to be more complex. The presence of a vascular surgeon will
      ensure a comprehensive clinical care.

PMID- 24910850
TI  - Pitfalls to be considered on the metabolomic analysis of biological samples by HR
      MAS.

PMID- 24910851
TI  - Expression of PKC iota affects neuronal differentiation of PC12 cells at least
      partly independent of kinase function.
AB  - Atypical PKC (aPKC) plays a role in establishing cell polarity and has been
      indicated in neuronal differentiation and polarization, including neurite
      formation in rat pheochromocytoma PC12 cells, albeit by unclear mechanisms. Here,
      the role of the aPKC isoform, PKC iota (PKCiota), in the early neuronal
      differentiation of PC12 cells was investigated. NGF-treated PC12 cells with
      stably expressed exogenous wild-type PKCiota showed decreased expression of a
      neuroendocrine marker, increased expression of a neuronal marker, and increased
      neurite formation. Stable expression of a kinase- inactive PKCiota, but not
      constitutively active PKCiota lacking a regulatory domain, had similar although
      less potent effects. Pharmacological inhibition of endogenous aPKC kinase
      activity in parental PC12 cells did not inhibit neurite formation, suggesting
      that some of the observed effects of PKCiota expression on neuronal
      differentiation are kinase- independent. Interestingly, exogenous expression of
      wild-type and kinase-inactive PKCiota had little effect on overall PKCiota
      activity, but caused a decrease in PKC zeta (PKCzeta) kinase activity, suggesting
      an interplay between the two isoforms that may underlie the observed results.
      Overall, these findings suggest that in PC12 and perhaps other neuroendocrine
      precursor cells, PKCiota influences an early differentiation decision between the
      neuroendocrine (chromaffin) and sympathetic neuron cell lineages, potentially by
      affecting PKCzeta function.

PMID- 24910852
TI  - Targeted MicroRNA Interference Promotes Postnatal Cardiac Cell Cycle Re-Entry.
AB  - Mammalian heart cells undergo a marked reduction in proliferative activity
      shortly after birth, and thereafter grow predominantly by hypertrophy. Our
      understanding of the molecular mechanisms underlying cardiac maturation and
      senescence is based largely on studies at the whole-heart level. Here, we
      investigate the molecular basis of the acquired quiescence of purified neonatal
      and adult cardiomyocytes, and use microRNA interference as a novel strategy to
      promote cardiomyocyte cell cycle re-entry. Expression of cyclins and cyclin
      dependent kinases (CDKs) and positive modulators were down-regulated, while CDK
      inhibitors and negative cell cycle modulators were up-regulated during postnatal
      maturation of cardiomyocytes. The expression pattern of microRNAs also changed
      dramatically, including increases in miR-29a, miR-30a and miR-141. Treatment of
      neonatal cardiomyocytes with miRNA inhibitors anti-miR-29a, anti-miR-30a, and
      antimiR-141 resulted in more cycling cells and enhanced expression of Cyclin A2
      (CCNA2). Thus, targeted microRNA interference can reactivate postnatal
      cardiomyocyte proliferation.

PMID- 24910854
TI  - Young Women's Sexual and Reproductive Health Post HPV Vaccination.
AB  - In the present study the authors sought to explore, in greater depth, the impact
      that HPV vaccination has on college-aged women's reproductive and sexual health.
      Qualitative interviews were conducted with 30 HPV-vaccinated, college women and
      analyzed for reoccurring themes. Although findings revealed that women's HPV
      related knowledge was suboptimal, most women correctly believed that they were
      still at risk for HPV after having received the vaccination. Women indicated that
      having the HPV vaccine made them more aware of sexually transmitted infections
      and prompted them to continue to take care of their sexual health. Women reported
      that having the HPV vaccine did not influence their condom use or birth control
      choices, and they believed that obtaining Pap smears was still important. These
      results help us to understand the impact of HPV vaccination on women's
      reproductive and sexual health. These findings are promising and reinforce the
      importance of educating women about behaviors that will help them maintain
      reproductive and sexually healthy lives.

PMID- 24910853
TI  - "hotdog", not "hot" "dog": The phonological planning of compound words.
AB  - Do we say dog when we say hotdog? In five experiments using the implicit priming
      paradigm, we assessed whether nominal compounds composed of two free morphemes
      like sawdust or fishbowl are prepared for production at the segmental level in
      the same way that two-syllable monomorphemic words (e.g. bandit) are, or instead
      as sequences of separable words (e.g. full bowl or grey dust). The experiments
      demonstrated that nominal compounds are planned as a single sequence, not as two
      sequences. Specifically, the onset of the second component of the compound (e.g.
      /d/ in sawdust) did not act as a primeable starting point, although comparable
      onsets did when that component was an independent word (grey dust). We conclude
      that there may be a dog in hotdog at the morpheme level, but not when
      phonological segments are prepared for production.

PMID- 24910855
TI  - Designing a Weight Gain Prevention Trial for Young Adults: The CHOICES Study.
AB  - BACKGROUND: Young adults are at risk for weight gain. Little is known about how
      to design weight control programs to meet the needs of young adults and few
      theory-based interventions have been evaluated in a randomized control trial. The
      Choosing Healthy Options in College Environments and Settings (CHOICES) study was
      funded to create a technology-based program for 2-year community college students
      to help prevent unhealthy weight gain. The purpose of this paper is to: 1)
      provide a brief background on weight-related interventions in young adults; 2)
      describe the study design for the CHOICES study, the conceptual model guiding the
      research and the CHOICES intervention; and 3) discuss implications of this
      research for health educators. TRANSLATION TO HEALTH EDUCATION PRACTICE: Our
      experiences from the CHOICES study will be useful in suggesting other theory
      based models and intervention strategies that might be helpful in programs
      attempting to prevent unhealthy weight gain in young adults. In addition, this
      paper discusses important considerations for working with 2-year colleges on this
      type of health promotion work.

PMID- 24910856
TI  - Laser desorption ionization mass spectrometry of peptides on a hybrid CHCA
      organic-inorganic matrix.
AB  - We report applications of new hybrid organic-inorganic silica based materials as
      laser desorption/ionization (LDI)-promoting surfaces for high-throughput
      identification of peptides. The driving force of our work was to design a new
      material composed of a conventional MALDI matrix covalently attached to silica
      with a high organic/inorganic ratio in order to improve the UV absorption by such
      LDI hybrid matrices. Amorphous CHCA-functionalized silica presenting an organic
      content up to 1.3 mmol g(-1) (around 40% in weight from TGA and elementary
      analysis measurements) gave very interesting LDI performances in terms of
      detection sensitivity as well as relative ionization discrepancy (spectral
      suppression) through the analyses of small synthetic peptide mixtures (550-1300
      Da) taking CHCA and amorphous silica as model matrices for control experiments. 

PMID- 24910857
TI  - Novel tentacle-type polymer stationary phase grafted with anion exchange polymer
      chains for open tubular CEC of nucleosides and proteins.
AB  - A novel and simple method for preparation of a tentacle-type polymer stationary
      phase grafted with polyethyleneimine (PEI) anion exchanger was developed for open
      tubular capillary electrochromatography (OT-CEC) of nucleosides and proteins. The
      polymeric stationary phase was prepared using 3-chloro-2-hydroxypropyl
      methacrylate (HPMA-Cl)-based reactive monomer. The preparation procedure included
      pretreatment of the capillary inner wall, silanization, in situ graft
      polymerization with HPMA-Cl and PEI modification. To compare with the tentacle
      type capillary column with PEI functionalization, a monolayer capillary column
      without PEI functionalization was also prepared. The electrochromatographic
      characterization of the prepared open tubular column was performed using
      alkylbenzenes. The electroosmotic flow (EOF) with regard to PEI concentrations
      and the running buffer pH was investigated. The separation conditions of the
      nucleosides and the proteins were optimized. The modified tentacle-type column
      with high anion exchange capacity has proven to afford better retention and
      resolution for the separation of nucleosides and proteins. The PEI
      functionalization column can also provide long-term stable use for biomolecule
      separation using a single capillary with relative standard deviation values of
      retention times of less than 2%. The results indicate that the present method for
      open tubular capillary preparation with a HPMA-Cl-based reactive monomer is
      promising for OT-CEC biomolecule separation. 

PMID- 24910858
TI  - Blueberry polyphenols prevent cardiomyocyte death by preventing calpain
      activation and oxidative stress.
AB  - The purpose of this study was to examine the efficacy of an aqueous wild
      blueberry extract and five wild blueberry polyphenol fractions on an in vitro
      model of heart disease. Adult rat cardiomyocytes were pretreated with extract and
      fractions, and then exposed to norepinephrine (NE). Cardiomyocyte hypertrophy,
      cell death, oxidative stress, apoptosis and cardiomyocyte contractile function as
      well as the activities of calpain, superoxide dismutase (SOD) and catalase (CAT)
      were measured in cardiomyocytes treated with and without NE and blueberry
      fraction (BF). Four of five blueberry fractions prevented cell death and
      cardiomyocyte hypertrophy induced by NE. Total phenolic fraction was used for all
      further analysis. The NE-induced increase in oxidative stress, nuclear
      condensation, calpain activity and lowering of SOD and CAT activities were
      prevented upon pretreatment with BF. Reduced contractile function was also
      significantly improved with BF pretreatment. Blueberry polyphenols prevent NE
      induced adult cardiomyocyte hypertrophy and cell death. The protective effects of
      BF may be in part attributed to a reduction in calpain activity and oxidative
      stress. 

PMID- 24910859
TI  - A child with uncontrollable bursts of laughter.

PMID- 24910860
TI  - Eating on impulse: the relation between overweight and food-specific inhibitory
      control.
AB  - OBJECTIVE: Consistent with the idea that impulsivity increases vulnerability to
      temptations of tasty high caloric food, less effective response inhibition is
      associated with overeating, overweight, and obesity. However, inefficient
      response inhibition mainly affects eating behavior when strong motivational urges
      to consume palatable food are simultaneously present. This study, therefore,
      examined whether overweight is associated specifically with inefficient response
      inhibition of food-related responses rather than with a general response
      inhibition deficiency. METHODS: Eighty-seven female participants (age: M = 26.17,
      SD = 10.9; body mass index (BMI: kg/m2): M = 22.28, SD = 4.34, range 13.86-39.86)
      performed both a Stop-Signal task with general stimuli to measure general
      response inhibition ability, and a Stop-Signal task with food-related pictures to
      measure ability to inhibit responses to food pictures. RESULTS: As expected, a
      higher BMI was associated with decreased inhibitory control over food-related
      responses. There was no association between BMI and general response inhibition.
      CONCLUSIONS: Overweight is not characterized by a general tendency to react
      impulsively, but instead by impulsive responding toward palatable food. The
      implication is that weight loss interventions need to focus on decreasing food
      specific impulsivity rather than on reducing general impulsivity.

PMID- 24910862
TI  - The Wolff-Parkinson-White syndrome: a very long follow-up.

PMID- 24910861
TI  - Science and the arts: Rock and research.

PMID- 24910863
TI  - Response.

PMID- 24910864
TI  - Response.

PMID- 24910866
TI  - Renewed energy.

PMID- 24910865
TI  - Don't feed the trolls.

PMID- 24910867
TI  - Integrity mentors.

PMID- 24910868
TI  - Environment: Accelerate research on land creation.

PMID- 24910869
TI  - What is the origin of the arrhythmia? A dysfunctional electrocardiograph.

PMID- 24910871
TI  - Replicant I - there's a storm coming: by caveman.

PMID- 24910870
TI  - Novel cosmetic patches for wrinkle improvement: retinyl  retinoate- and ascorbic
      acid-loaded dissolving microneedles.
AB  - OBJECTIVE: To evaluate wrinkle improvement and safety of a novel cosmetic
      dissolving microneedle patches loaded with two active compounds with different
      hydrophilicities, namely ascorbic acid and retinyl retinoate. METHODS: Clinical
      studies were performed on 24 Korean women for 12 weeks. Patients in group A were
      treated with retinyl retinoate-loaded dissolving microneedle patches on the left
      eye crow's feet area, and patients in group B were treated with ascorbic
      acidloaded patches on the right eye crow's feet area twice daily. Wrinkle
      improvement was evaluated by skin Visiometer SV 600. RESULTS: Both the retinyl
      retinoate- and ascorbic acid-loaded dissolving microneedle patches demonstrated
      statistically significant differences in all Visiometer R-values (P < 0.05). In
      particular, highly significant differences were shown at R1 (skin roughness) and
      R5 (arithmetic average roughness) (P < 0.001). Also, there were no side effects
      such as allergies or irritant contact dermatitis. CONCLUSION: Retinyl retinoate
      and ascorbic acid were successfully loaded into dissolving microneedles and used
      to produce novel cosmetic patches. These novel patches can be used efficiently in
      cosmetics given their patient usability, safety and effectiveness in wrinkle
      improvement.

PMID- 24910872
TI  - Assessing dystrophies and other muscle  diseases at the nanometer scale by atomic
      force microscopy.
AB  - AIM: Atomic force microscopy nanoindentation of myofibers was used to assess and
      quantitatively diagnose muscular dystrophies from human patients. MATERIALS &
      METHODS: Myofibers were probed from fresh or frozen muscle biopsies from human
      dystrophic patients and healthy volunteers, as well as mice models, and Young's
      modulus stiffness values were determined. RESULTS: Fibers displaying abnormally
      low mechanical stability were detected in biopsies from patients affected by 11
      distinct muscle diseases, and Young's modulus values were commensurate to the
      severity of the disease. Abnormal myofiber resistance was also observed from
      consulting patients whose muscle condition could not be detected or unambiguously
      diagnosed otherwise. DISCUSSION & CONCLUSION: This study provides a proof-of
      concept that atomic force microscopy yields a quantitative read-out of human
      muscle function from clinical biopsies, and that it may thereby complement
      current muscular dystrophy diagnosis.

PMID- 24910873
TI  - Escheriosome-mediated cytosolic delivery  of PLK1-specific siRNA: potential in 
      treatment  of liver cancer in BALB/c mice.
AB  - AIM: In the present study, the anticancer efficacy of a novel escheriosome-based
      formulation of PLK1-specific siRNA was evaluated against liver cancer in BALB/c
      mice. MATERIALS & METHODS: The escheriosome-based siRNA nanoparticles were
      prepared using lipids isolated from Escherichia coli. The escheriosomes were
      characterized for size, surface charge and stability. The anticancer potential of
      PLK1-specific siRNA formulation was ascertained on the basis of expression of pro
      /anti-apoptotic factors and histopathological studies. RESULTS: The escheriosome
      entrapped siRNA was found to be released in surrounding milieu in a sustained
      manner. The nanoformulation was successful in modulating proapoptotic factors and
      eventually helped in better survival of the treated animals. CONCLUSION: Our data
      demonstrate the efficacy of systemically administered siRNA in the treatment of
      experimental liver cancer. This novel therapeutic strategy may be applicable to a
      broad range of cancers in patients with the obstinate form of the disease.

PMID- 24910874
TI  - Therapeutic efficacy of intravenously  administered transferrin-conjugated 
      dendriplexes on prostate carcinomas.
AB  - AIM: Improved treatments for prostate cancer are critically needed in order to
      overcome metastasis and lethal recurrence. Intravenously administered gene
      therapy would be an attractive anticancer treatment strategy; however, the lack
      of suitable carrier systems able to selectively deliver therapeutic genes to
      tumors has so far limited this investigation. Given that transferrin receptors
      are overexpressed on prostate cancer cells, the purpose of this study is to
      determine whether transferrin-conjugated dendriplexes encoding TNF-alpha, TNF
      related apoptosis-inducing ligand and IL-12 would suppress the growth of prostate
      cancer cell lines in vitro and in vivo. MATERIALS & METHODS: Transferrin
      conjugated dendriplexes encoding TNF-alpha, TNF-related apoptosis-inducing ligand
      and IL-12 were intravenously administered to mice bearing subcutaneous PC-3 and
      DU145 tumors. RESULTS: The administration of the transferrin-conjugated
      generation 3 diaminobutyric polypropylenimine dendriplex encoding TNF-a resulted
      in tumor suppression for 60% of PC-3 and 50% of DU145 prostate tumors.
      CONCLUSION: These dendriplexes hold great potential as a novel approach for
      prostate cancer therapy.

PMID- 24910876
TI  - Mucoadhesive and enzymatic inhibitory  nanoparticles for transnasal insulin
      delivery.
AB  - AIM: To develop a novel nanocarrier with mucoadhesion and enzymatic inhibition
      for transnasal insulin delivery. METHODS & METHODS: The physicochemical
      characterization of the nanoparticles included size and morphology, as well as
      mucoadhesion and enzymatic inhibition. The in vitro release of insulin from the
      nanoparticles was evaluated in 3 mg/ml glucose medium. The cytocompatibility of
      the nanoparticles was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. The interactions of the nanoparticles with
      Caco-2 cells and nasal epithelia, and the effect of the nanoparticles on
      transnasal insulin delivery were estimated. RESULTS: The nanoparticles were
      spherical in shape, with an average size of 100 nm, and presented strong
      enzymatic inhibitory activity and high mucin adsorption ability. The
      insulinloaded nanoparticles showed the rapid insulin release in 3 mg/ml glucose
      medium. The nanoparticles were noncytotoxic to Caco-2 cells. Furthermore, the
      insulin-loaded nanoparticles overcame mucosal barriers and significantly
      decreased plasma glucose levels.

PMID- 24910875
TI  - Liposomes containing NY-ESO-1/tetanus  toxoid and adjuvant peptides targeted to 
      human dendritic cells via the Fc receptor for  cancer vaccines.
AB  - AIM: To improve the immunological response against tumors, a vaccine based on
      nanoliposomes targeted to the Fcg-receptor was developed to enhance the
      immunogenicity of tumor-associated antigens (TAAs). MATERIALS & METHODS: Using
      human dendritic cells in vitro, a fragment of the TAA NY-ESO-1 combined with a T
      helper peptide from the tetanus toxoid encapsulated in nanoliposomes was
      evaluated. In addition, peptides Palm-IL-1 and MAP-IFN-g were coadministered as
      adjuvants to enhance the immunological response. RESULTS: Coadministration of
      Palm-IL-1 or MAP-IFN-g peptide adjuvants and the hybrid NY-ESO-1-tetanus toxoid
      (soluble or encapsulated in nanoliposomes without targeting) increased
      immunogenicity. However, the most potent immunological response was obtained when
      the peptide adjuvants were encapsulated in liposomes targeted to human dendritic
      cells via the Fc receptor. CONCLUSION: This targeted vaccine strategy is a
      promising tool to activate and deliver antigens to dendritic cells, thus
      improving immunotherapeutic response in situations in which the immune system is
      frequently compromised, as in advanced cancers.

PMID- 24910877
TI  - Nanoencapsulation of DMSA monoester  for better therapeutic efficacy of the 
      chelating agent against arsenic toxicity.
AB  - AIMS: Exposure to toxic metals remains a widespread occupational and
      environmental problem in world. Chelation therapy is a mainstream treatment used
      to treat heavy metal poisoning. This paper describes the synthesis,
      characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic
      acid (MiADMSA)-encapsulated polymeric nanoparticles as a detoxifying agent for
      arsenic poisoning. MATERIALS & METHODS: Polymeric nanoparticles entrapping the
      DMSA monoester, which can evade the reticulo-endothelial system and have a long
      circulation time in the blood, were prepared. Particle characterization was
      carried out by transmission electron microscopy and dynamic light scattering. An
      in vivo study was conducted to investigate the therapeutic efficacy of MiADMSA
      encapsulated polymeric nanoparticles (nano- MiADMSA; 50 mg/kg orally for 5 days)
      and comparison drawn with bulk MiADMSA. Swiss albino mice exposed to sodium
      arsenite for 4 weeks were treated for 5 days to evaluate alterations in blood,
      brain, kidney and liver oxidative stress variables. The study also evaluated the
      histopathological changes in tissues and the chelating potential of the
      nanoformulation. RESULTS: Our results show that nano-MiADMSA have a narrow size
      distribution in the 50-nm range. We observed an enhanced chelating potential of
      nano-MiADMSA compared with bulk MiADMSA as evident in the reversal of biochemical
      changes indicative of oxidative stress and efficient removal of arsenic from the
      blood and tissues. Histopathological changes and urinary 8-OHdG levels also prove
      better therapeutic efficacy of the novel formulation for arsenic toxicity.
      CONCLUSION: The results from our study show better therapeutic efficacy of nano
      MiADMSA in removing arsenic burden from the brain and liver.

PMID- 24910879
TI  - Alternatives to animal experiments.

PMID- 24910880
TI  - Retraction notice to "Sperm ultrastructure in two species of Panorpa and one
      Bittacus(Mecoptera)" [Micron 41(6)(2010)622-632].

PMID- 24910881
TI  - Swine flu vaccination programme begins.

PMID- 24910882
TI  - Horror and disgust ... traumatic...

PMID- 24910883
TI  - How many patients does it take to engage a hospital?

PMID- 24910884
TI  - Falling for successful fall projects.

PMID- 24910885
TI  - ECRI tackles patient safety issues.

PMID- 24910886
TI  - PSOs tout benefits of membership.

PMID- 24910878
TI  - Bench-to-bedside translation of magnetic  nanoparticles.
AB  - Magnetic nanoparticles (MNPs) are a new and promising addition to the spectrum of
      biomedicines. Their promise revolves around the broad versatility and
      biocompatibility of the MNPs and their unique physicochemical properties. Guided
      by applied external magnetic fields, MNPs represent a cutting-edge tool designed
      to improve diagnosis and therapy of a broad range of inflammatory, infectious,
      genetic and degenerative diseases. Magnetic hyperthermia, targeted drug and gene
      delivery, cell tracking, protein bioseparation and tissue engineering are but a
      few applications being developed for MNPs. MNPs toxicities linked to shape, size
      and surface chemistry are real and must be addressed before clinical use is
      realized. This article presents both the promise and perils of this new
      nanotechnology, with an eye towards opportunity in translational medical science.

PMID- 24910887
TI  - Identification of a first enzymatic activator of a 17beta-hydroxysteroid
      dehydrogenase.
AB  - Small molecule activators that directly modulate the activity of an enzyme are
      uncommon entities, and such activators had never yet been identified for any
      17beta-hydroxysteroid dehydrogenase (17beta-HSD). We hereby report the fortuitous
      discovery of a steroid derivative that caused an up to 3-fold increase in the
      activity of 17beta-HSD12. The stimulation of estrone to estradiol conversion has
      been characterized in intact and homogenized stably transfected HEK-293 cells and
      has also been observed in T47D breast cancer cells. Structure-activity
      relationships closely linked to the nature of the substituent on the
      [1,3]oxazinan-2-one ring of an estradiol derivative emerged from this study and
      may help in the identification of a previously unsuspected endogenous activation
      of 17beta-HSD12. This activator will therefore be a useful tool to study this
      relatively unknown enzyme as well as the possible activation of other 17beta-HSD
      family members. 

PMID- 24910889
TI  - Excited state equilibrium induced lifetime extension in a dinuclear platinum(II)
      complex.
AB  - Covalently linking two square planar platinum(II) centers using two pyrazolate
      bridging ligands allows the filled dz(2) orbitals on each Pt center to overlap,
      producing a Pt-Pt sigma interaction and new low energy dsigma* -> pi* metal-metal
      to-ligand charge transfer (MMLCT) transitions terminating on an appropriate pi
      acceptor ligand such as 2-phenylpyridine (ppy). In an effort to extend the
      lifetime of the associated MMLCT excited state, we decided to append piperidinyl
      naphthalimide (PNI) chromophores to the 2-phenylpyridine charge transfer ligands.
      This structural modification introduces low-lying PNI-based triplet states
      serving as long-lived triplet population reservoirs, thermally capable of
      repopulating the charge transfer state at room temperature (RT), thereby
      extending its excited state lifetime. Specifically, [Pt(PNI-ppy)(MU-Ph2pz)]2 (1),
      where PNI-ppy is N-(2-phenylpyridine)-4-(1-piperidinyl)naphthalene-1,8
      dicarboximide and Ph2pz is 3,5-diphenylpyrazolate, was synthesized and
      structurally characterized. The static and dynamic photophysical behavior of 1
      was directly compared to the MMLCT complex [Pt(ppy)(MU-Ph2pz)]2 (2), lacking the
      PNI substituents, as well as the naked PNI-ppy ligand 3, intended to
      independently model the MMLCT and NI excited state properties, respectively.
      Ultimately, experimental evidence for the presence of both the (3)PNI and
      (3)MMLCT excited states in 1 were revealed at RT in nanosecond transient
      absorbance and time-resolved photoluminescence spectroscopy, respectively.
      Temperature-dependent transient absorption spectroscopy permitted the extraction
      of an energy gap of 1740 cm(-1) between the MMLCT and PNI triplet states in 1
      along with the time constants associated with the interconversions between the
      various excited states resident on this complex chromophore, ultimately decaying
      back to the ground state with a time constant of 65 MUs at RT. 

PMID- 24910890
TI  - LiMnBO3 nanobeads as an innovative anode material for high power lithium ion
      capacitor applications.
AB  - A novel approach was made to fabricate lithium ion hybrid capacitor (Li-HC)
      having LiMnBO3 nanobead (LMB-NB) anode and polyaniline nanofiber (PANI) cathode
      in 1 M LiPF6 organic electrolyte. LMB-NB and PANI nanofibers were synthesized
      using urea assisted microwave-solvothermal method and chemical polymerization
      process, respectively. The PANI/LMB-NB cell showed improved electrochemical
      capacitive behavior as compared to activated carbon (AC)/LMB-NB cell due to the
      characteristic conductivity and the morphological feature of PANI as well as LMB
      NB electrodes. A discharge capacitance (DCcell) of ~125 F g(-1) was obtained at a
      current density of 1 A g(-1) between the potential range 0 and 3 V for PANI/LMB
      NB cell, while AC/LMB-NB cell delivered only 77 F g(-1) at the same current
      density. Moreover, PANI/LMB-NB cell exhibited excellent rate performance with the
      DCcell of about 55 F g(-1) at 2.25 A g(-1) and still retained 94% of the initial
      value after 30 000 charge-discharge cycles. In addition, maximum energy and power
      densities of 42 Wh kg(-1) and 5350 W kg(-1), respectively, were achieved from
      PANI/LMB-NB cell. The obtained DCcell, energy, and power densities along with
      prolonged cyclic life for PANI/LMB-NB cell are some of the best ever reported
      values for Li-HC as compared to the cells constructed with various lithium
      intercalating materials. 

PMID- 24910888
TI  - Sustainability for the nation: resource connections and governance linkages.

PMID- 24910891
TI  - Dietary magnesium intake and risk of cancer: a meta-analysis of epidemiologic
      studies.
AB  - The aim of this study was to investigate the association between dietary
      magnesium and the risk of overall cancer using a meta-analysis. We searched
      PubMed, SCOPUS, and the Cochrane Review through November 2012. All the articles
      searched were independently reviewed by 3 authors based on predetermined
      selection criterion. A total of 13 epidemiologic studies, 6 case-control studies,
      and 7 prospective cohort studies involving 1,236,004 participants were included
      in the final analysis. When all studies were pooled, the relative risk (RR) of
      overall cancer for the highest level of dietary magnesium intake was 0.801 [95%
      confidence interval (CI): 0.664-0.966) compared with the lowest level of dietary
      magnesium intake. In subgroup meta-analyses by study design, there was a
      significant inverse association between dietary magnesium and the risk of cancer
      in case-control studies (RR = 0.663, 95% CI: 0.475-0.925), whereas there was no
      significant association in prospective cohort studies (RR = 0.888, 95% CI: 0.745
      1.060). Furthermore, there was a significant preventive effect of dietary
      magnesium for colorectal cancer (RR = 0.775, 95% CI: 0.655-0.919), but not for
      other cancer. Our meta-analysis showed that higher dietary magnesium intake seems
      to have a protective effect for cancer, especially colorectal cancer and in
      females. 

PMID- 24910892
TI  - "Click" synthesis of nona-PEG-branched triazole dendrimers and stabilization of
      gold nanoparticles that efficiently catalyze p-nitrophenol reduction.
AB  - Two new water-soluble 1,2,3-triazole-containing nona-PEG-branched dendrimers are
      obtained with nine intradendritic 1,2,3-triazoles (trz). Addition of HAuCl4 in
      water to these dendrimers quantitatively leads to the intradendritic formation of
      AuCl3(trz) moieties subsequent to complete Cl(-) substitution by trz on Au(III),
      whereas the analogous complexation reaction of AuCl3 with a linear PEG trz ligand
      forms only an equilibrium between trz-coordinated Au(III) and Au(III) that is not
      coordinated to trz. Reduction of the dendrimer-Au(III) complexes to Au(0) by
      NaBH4 then leads to stabilization of gold nanoparticles (AuNPs) in water. The
      sizes of the AuNPs stabilized by the dendritic macromolecules are further
      controlled between 1.8 and 12 nm upon selecting the stoichiometry of Au(III)
      addition per dendritic trz followed by NaBH4 reduction. With a 1:1 Au/trz
      stoichiometry, the AuNP size depends on the length of the PEG tether of the
      dendrimer; small dendrimer-encapsulated AuNPs are formed with PEG2000, whereas
      large AuNPs are formed with PEG550. With Au/trz stoichiometries larger than
      unity, Au(III) is reduced outside the macromolecule, resulting in the formation
      of large interdendritically stabilized AuNPs. The formation of very small and
      only mildly stabilized AuNPs by neutral hydrophilic triazole ligands offers an
      opportunity for very efficient p-nitrophenol reduction by NaBH4 in water at the
      AuNP surface. 

PMID- 24910893
TI  - Correction to: Hierarchically Built Hetero-superstructure Arrays with
      Structurally Controlled Material Compositions.

PMID- 24910894
TI  - Verbal mistreatment of the elderly.
AB  - Elder mistreatment is expected to rise with the aging of the American population.
      To date, the association between specific forms of mistreatment and decreased
      quality of life is poorly understood. The aim of the present study was to explore
      the association between verbal mistreatment among elderly individuals and
      depression and quality of life. A sample of 142 older adults (40% male) aged 65
      or over was enrolled from a large medical practice and academic dental practice,
      mean (SD) age = 74.88 (6.98) years. Thirty-eight percent of the sample reported
      verbal mistreatment. Controlling for sociodemographic characteristics and
      depression, verbal mistreatment was a significant predictor of social functioning
      (r = -.28, p < .001), mental health (r = -.25, p < .001), and role limitations OR
      = 3.02, 95% CI [1.34-6.77]. The present findings highlight the prevalence of
      verbal mistreatment of elderly individuals.

PMID- 24910895
TI  - Observational measure of elder self-neglect.
AB  - The purpose of this study was to improve measurement of elder self-neglect by
      testing the psychometric properties of the Elder Self-Neglect Assessment (ESNA).
      Social workers, case managers, and adult protective services providers from 13
      Illinois agencies completed a 77-item assessment for 215 clients suffering from
      self neglect. Analyses used Rasch item response theory and traditional validation
      approaches to test for dimensionality, model fit, and additional construct
      validation, resulting in a 62-item assessment. The ESNA met Rasch fit criteria
      with good internal consistency, item reliability, and construct validity. A 25
      item short form also met Rasch criteria. A hierarchy of items associated with
      severity of abuse was produced by frequency of occurrence. ESNA indicators of
      self-neglect align into two broad categories: behavioral characteristics and
      environmental factors, which must be accounted for in a comprehensive evaluation.
      Theoretical refinements developed using the empirically generated item hierarchy
      may help to improve assessment and intervention. 

PMID- 24910896
TI  - Perceptions of Organ Donors and Willingness to Donate Organs Upon Death: A Test
      of the Prototype/Willingness Model.
AB  - Understanding people's organ donation decisions may narrow the gap between organ
      supply and demand. In two studies, participants who had not recorded their
      posthumous organ donation decision (Study 1 N = 210; Study 2 N = 307) completed
      items assessing Prototype/Willingness Model (PWM) (attitude, subjective norm,
      donor prototype favorability and similarity, willingness) constructs. Attitude,
      subjective norm, and prototype similarity predicted willingness to donate.
      Prototype favorability and a prototype favorability x similarity interaction
      predicted willingness (Study 2). These findings provide support for the PWM in
      altruistic health contexts, highlighting the importance of people's perceptions
      about organ donors in their donation decisions.

PMID- 24910897
TI  - Three-step metal-promoted allene-based preparation of bis(heterocyclic)
      cyclophanes from carbonyl compounds.
AB  - A straightforward metal-mediated method for the synthesis of bis(dihydrofuryl)
      cyclophane scaffolds from carbonyl compounds has been developed. The combination
      of the dihydrofuran moiety with different heterocycles such as beta-lactams and
      sugars allows high levels of skeletal diversity. The process comprises indium
      promoted one-pot carbonyl bis(allenylation) and gold- or palladium-catalyzed
      double cyclization in the resulting bis(allenols), followed by selective
      ruthenium-catalyzed macrocyclization. In some cases, the method has been
      successfully applied to the synthesis of the challenging Z-isomers. The E- versus
      Z-stereochemistry of the metathesis-formed double bonds could not be assigned
      taking into consideration the usual coupling constants criteria, but a diagnostic
      based on the chemical shifts of the two olefinic protons located at the
      macrocyclic double bond was established. 

PMID- 24910898
TI  - Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal
      neovascularization in rats.
AB  - BACKGROUND: To evaluate the effects of sub-conjunctivally applied interleukin-6
      receptor (IL-6R) antibody (tocilizumab) on alkali burn induced corneal
      neovascularization (CNV) in rats. METHODS: Alkali burn induced corneal
      neovascularization was created in 24 right eyes of 24 rats. The rats were then
      randomized into 2 groups. Group 1 received sub-conjunctival injection of 4 mg/0.2
      ml tocilizumab and Group 2 received sub-conjunctival injection of 0.2 ml normal
      saline at the 5th day of alkali burn. The corneal surface area invaded with
      neovascular vessels were calculated on photographs. The rats were sacrificed and
      the corneas were excised at the15th day. The corneal specimens were stained with
      hemotoxylin-eosin to evaluate tissue morphology and with Willebrand factor (vWF)
      to evaluate microvascular structures immunohistochemically. Vascular endothelial
      growth factor (VEGF) expression was analyzed by ELISA. RESULTS: The percent area
      of CNV was 26.9% in Group 1 and 56.5% in Group 2 (p < 0.001). The histological
      evaluation showed that the corneal structures were not visibly altered by sub
      conjuntival tocilizumab injection. Group 1 showed significantly lower corneal
      inflammation score than Group 2 (p < 0.001). The number of vessels stained with
      vWF were significantly higher in Group 2 than Group 1 (15.23 and 5.46,
      respectively; p < 0.001). ELISA analyses showed that corneal VEGF levels were
      significantly lower in Group 1 compared to Group 2 (p = 0.013) CONCLUSION: The
      present data demonstrated first time the beneficial effects of sub-conjunctival
      tocilizumab on decreasing CNV in alkali burn model of the rat cornea. Further
      studies are warranted to confirm these findings for the clinical application.

PMID- 24910899
TI  - Chemical constituents from Gouania longipetala and Glyphaea brevis.
AB  - Five compounds were isolated altogether from the two medicinal plants. Glycerol
      monotricosanoate (1), palmarumycin BG1 (2) and de-O-methyllasiodiplodin (3) were
      isolated from Gouania longipetala. In addition, epicatechin (4) and its dimer
      procyanidin B2 (5) were isolated from the stem bark of Glyphaea brevis. Their
      structures were elucidated by using spectroscopic experiments. They exhibited
      radical scavenging and moderate antibacterial effects.

PMID- 24910900
TI  - HPLC-MS/MS method for the measurement of insecticide degradates in baby food.
AB  - A solid phase extraction method was developed to isolate four insecticide
      degradates from baby food that were measured subsequently using high-performance
      liquid chromatography-tandem mass spectrometry. The degradates [parent
      insecticide] measured were malathion dicarboxylic acid [malathion], 3,5,6
      trichloro-2-pyridinol [chlorpyrifos, chlorpyrifos methyl] (TCPy), cis/trans-3
      (2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid [permethrin,
      cypermethrin, cyfluthrin], and 3-phenoxybenzoic acid [general pyrethroid]. All
      degradates produced recoveries between 80 and 120% except TCPy in fruit (122%
      recovery), and all relative standard deviations were <16%. Use of this method
      demonstrated that insecticide degradates were found in baby foods frequently
      purchased in the United States, supporting the need for this method. These data
      will assist in differentiating whether biomarker levels of insecticide
      metabolites are the result of exposures to the toxic insecticide or its preformed
      degradate. 

PMID- 24910901
TI  - Exendin-4 alleviates retinal vascular leakage by protecting the blood-retinal
      barrier and reducing retinal vascular permeability in diabetic Goto-Kakizaki
      rats.
AB  - The breakdown of the inner endothelial blood-retinal barrier (BRB) and subsequent
      retinal vascular leakage are the main causes of vision loss due to diabetic
      retinopathy (DR). Exendin-4 (E4) is a long-acting agonist of the glucagon-like
      peptide 1 hormone receptor (GLP-1R) that is widely used in clinics and has shown
      a neuroprotective effect. Our previous studies demonstrated the protective effect
      of E4 in early experimental DR; however, the molecular and cellular mechanisms
      that mediate this protective effect are not fully known. The BRB plays a key role
      in DR. We speculated that E4 may exert its protective effects on the BRB. To test
      this hypothesis, E4 (0.1 MUg/2 MUL/eye) or vehicle were intravitreally injected
      into diabetic Goto-Kakizaki(GK) rats and control animals. The results revealed
      that E4 significantly inhibited the reductions in electroretinogram (ERG)
      amplitudes in the GK rats, particularly in the b-wave and oscillatory potentials
      (OPs). E4 upregulated retinal GLP-1R expression and downregulated the expressions
      of placental growth factor (PLGF) and vascular endothelial growth factor (VEGF)
      via the ERK and AKT/PKB pathways. Decreases in tight junction protein (i.e.,
      claudin-5 and occludin) expression and increases in Evans blue permeation (EBP)
      were inhibited by E4. Similar results were also found in primary rat Muller cells
      in high glucose concentration cultures in vitro. We conclude that E4 may protect
      the BRB from diabetic insults by decreasing PLGF and ICAM-1 expression and
      maintaining the integrity of the BRB. Thus, E4 treatment may be an effective
      therapeutic approach for DR. 

PMID- 24910903
TI  - Sleep quality in women with systemic lupus erythematosus: contributing factors
      and effects on health-related quality of life.
AB  - AIM: Sleep quality disturbances are common in patients with systemic lupus
      erythematosus (SLE). We evaluated sleep quality and its contributors in women
      with SLE. Also we evaluated the effects of sleep quality disturbance on patients'
      health-related quality of life (HRQoL). METHODS: Sleep quality was assessed in 77
      women with SLE (age 36.5 +/- 10.1 years) using the Pittsburgh Sleep Quality Index
      (PSQI). Disease activity and cumulative disease damage were assessed with
      standard indices. Patients completed the Hospital Anxiety and Depression Scale
      and LupusQoL. Univariate and multivariate analyses were performed to find
      contributors of poor sleep quality and association of sleep quality with HRQoL.
      RESULTS: Poor sleep quality was present in 44 patients (57.1%). Poor sleepers
      were older (P = 0.015) and had higher body mass index (P = 0.027) and more severe
      anxiety (P < 0.001) and depression symptoms (P < 0.007) compared with good
      sleepers. In the logistic regression model, age (beta = 1.16, P = 0.006), disease
      activity (beta = 1.10, P = 0.050), and anxiety/depression composite score (beta =
      1.16, P = 0.008) were independent contributors of poor sleep quality. Poor
      sleepers had impaired HRQoL in almost all domains of the LupusQoL than good
      sleepers (P < 0.05). CONCLUSION: Poor sleep quality is common in women with SLE
      and significantly impairs their HRQoL. Age, disease activity and psychological
      factors were determinants of sleep quality in our study. Studies with objective
      sleep measures as well as interventional studies are warranted in this regard.

PMID- 24910904
TI  - Acute myocarditis: multiparametric cardiac MR imaging.
AB  - PURPOSE: To evaluate the diagnostic value of cardiac magnetic resonance (MR)
      imaging at 3 T in patients suspected of having acute myocarditis by using a
      multiparametric cardiac MR imaging approach including T1 relaxation time as an
      additional tool for tissue characterization. MATERIALS AND METHODS: Ethics
      commission approval was obtained for this prospective study, and written informed
      consent was obtained from all subjects. Twenty four patients with acute
      myocarditis (mean age +/- standard deviation, 34.7 years +/- 15.1; 75% men) and
      42 control subjects (mean age, 38.7 years +/- 10.2; 64% men) were included.
      Cardiac MR imaging approaches included relative T2 short tau inversion-recovery
      signal intensity ratio (T2 ratio), early gadolinium enhancement ratio, late
      gadolinium enhancement, native T1 relaxation times, and extracellular volume
      fraction. Receiver operating characteristic analysis was performed to compare
      diagnostic performance. The reference standard was the clinical evidence for
      acute myocarditis. RESULTS: Native T1 relaxation times were significantly longer
      in patients with acute myocarditis than in control subjects (1185.3 msec +/- 49.3
      vs 1089.1 msec +/- 44.9, respectively; P < .001). Areas under the curve of native
      T1 relaxation times (0.94) were higher compared with those of other cardiac MR
      parameters (late gadolinium enhancement, 0.90; T2 ratio, 0.79; extracellular
      volume fraction, 0.71; early gadolinium enhancement ratio, 0.63; P = .390, .018,
      .002, and < .001, respectively). Sensitivity (92%), specificity (91%), and
      diagnostic accuracy (91%) for native T1 relaxation times (cutoff, 1140 msec) were
      equivalent compared with those of the established combined Lake Louise criteria
      (sensitivity, 92%; specificity, 80%; diagnostic accuracy, 85%). CONCLUSION:
      Diagnostic performance with native T1 mapping was superior to that with T2 ratio
      and early gadolinium enhancement ratio, and specificity was higher with native T1
      mapping than that with Lake Louise criteria. This study underlines the potential
      of native T1 relaxation times to complement current cardiac MR approaches in
      patients suspected of having acute myocarditis.

PMID- 24910905
TI  - Comment on "mechanical properties of giant liposomes compressed between two
      parallel plates: impact of artificial actin shells".

PMID- 24910902
TI  - Bone morphogenetic protein 2: a potential new player in the pathogenesis of
      diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is one of the most common complications of diabetes
      mellitus. Vision loss in DR principally occurs due to breakdown of the blood
      retinal barrier (BRB), leading to macular edema, retinal detachment and inner
      retinal and vitreous hemorrhage. Several growth factors have been shown to play
      crucial role in the development of these vascular changes; however, the cellular
      and molecular mechanisms of DR are not yet fully revealed. In the current study
      we investigated the role of bone morphogenetic protein-2 (BMP2) in DR. We
      examined the changes in the protein levels of BMP2 in human vitreous and retina
      in addition to the mouse retina of streptozotocin-induced diabetes. To detect the
      source of BMP2 during diabetes, human retinal endothelial cells (hRECs) were
      subjected to high glucose (HG) for 5 days and levels of BMP2 protein were
      analyzed in conditioned media of these cells relative to control. We also
      evaluated the effect of BMP2 on the levels of VEGF in cultured rat Muller cells
      (rMC1). In addition, we tested the pro-inflammatory effects of BMP2 by examining
      its effect on leukocyte adhesion to cultured hRECs, and levels of adhesion
      molecules and cytokines production. Finally, the effect of different
      concentrations of BMP2 on permeability of confluent monolayer of hRECs was
      evaluated using FITC-Dextran flux permeability assay and by measuring
      Transcellular Electrical Resistance (TER) using Electric Cell-substrate Impedance
      Sensing (ECIS). Our results show, for the first time, the up-regulation of BMP2
      in diabetic human and mouse retinas in addition to its detection in vitreous of
      patients with proliferative DR (72 +/- 7 pg/ml). In vitro, hRECs showed
      upregulation of BMP2 in HG conditions suggesting that these cells are a potential
      source of BMP2 in diabetic conditions. Furthermore, BMP2 induced VEGF secretion
      by Muller cells in-vitro; and showed a dose response in increasing permeability
      of cultured hRECs. Meanwhile, BMP2 pro-inflammatory effects were recognized by
      its ability to induce leukocyte adhesion to the hRECs, intercellular adhesion
      molecule-1 (ICAM-1) and upregulation of interleukin-6 and 8 (IL-6 and IL-8).
      These results show that BMP2 could be a contributing growth factor to the
      development of microvascular dysfunction during DR via enhancing both pro
      angiogenic and inflammatory pathways. Our findings suggest BMP2 as a potential
      therapeutic target to prevent/treat DR. 

PMID- 24910906
TI  - Nonionic cyclodextrin based binary system with upper and lower critical solution
      temperature transitions via supramolecular inclusion interaction.
AB  - A nonionic binary aqueous interaction system consisting of beta-cyclodextrin
      trimer (beta-CD3) and naphthalene-terminated poly(ethylene glycol) (PEG-NP2),
      which has tunable upper critical solution temperature (UCST) behavior around room
      temperature and lower critical solution temperature (LCST) behavior at high
      temperature, was investigated. In the UCST transition, gel-like aggregates form
      because of supramolecular inclusion complexation between beta-CD3 and PEG-NP2.
      During LCST transition, PEG-NP2 becomes insoluble in water, which results in its
      precipitation. The effects of concentration, stoichiometry of the two components,
      and electrolyte on UCST behavior are discussed. This study provides a new
      nonionic thermoresponsive material. 

PMID- 24910908
TI  - Composition and leaching of construction and demolition waste: inorganic elements
      and organic compounds.
AB  - Thirty-three samples of construction and demolition waste collected at 11
      recycling facilities in Denmark were characterised in terms of total content and
      leaching of inorganic elements and presence of the persistent organic pollutants
      PCBs and PAHs. Samples included (i) "clean" (i.e. unmixed) concrete waste, (ii)
      mixed masonry and concrete, (iii) asphalt and (iv) freshly cast concrete cores;
      both old and newly generated construction and demolition waste was included. PCBs
      and PAHs were detected in all samples, generally in non-critical concentrations.
      Overall, PAHs were comparable to background levels in urban environments. "Old"
      and "new" concrete samples indicated different PCB congener profiles and the
      presence of PCB even in new concrete suggested that background levels in raw
      materials may be an issue. Significant variability in total content of trace
      elements, even more pronounced for leaching, was observed indicating that the
      number of analysed samples may be critical in relation to decisions regarding
      management and utilisation of the materials. Higher leaching of chromium,
      sulphate and chloride were observed for masonry-containing and partly carbonated
      samples, indicating that source segregation and management practices may be
      important. Generally, leaching was in compliance with available leaching limits,
      except for selenium, and in some cases chromium, sulphate and antimony. 

PMID- 24910907
TI  - Spherical polystyrene-supported chitosan thin film of fast kinetics and high
      capacity for copper removal.
AB  - In order to accelerate the kinetics and improve the utilization of the surface
      active groups of chitosan (CS) for heavy metal ion removal, sub-micron-sized
      polystyrene supported chitosan thin-film was synthesized by the electrostatic
      assembly method. Glutaraldehyde was used as cross-linking agent. Chitosan thin
      film was well coated onto the surface of the polystyrene (PS) beads characterized
      by scanning electron microscopy (SEM) and energy dispersive X-ray (EDX). Their
      adsorption toward Cu(II) ions was investigated as a function of solution pH,
      degree of cross-linking, equilibrium Cu(II) ions concentration and contact time.
      The maximum adsorptive capacity of PS-CS was 99.8 mg/g in the adsorption isotherm
      study. More attractively, the adsorption equilibrium was achieved in 10 min,
      which showed superior properties among similar adsorbents. Continuous adsorption
      desorption cyclic results demonstrated that Cu(II)-loaded PS-CS can be
      effectively regenerated by a hydrochloric acid solution (HCl), and the
      regenerated composite beads could be employed for repeated use without
      significant capacity loss, indicating the good stability of the adsorbents. The
      XPS analysis confirmed that the adsorption process was due to surface complexes
      with atoms of chitosan. Generally, PS beads could be employed as a promising host
      to fabricate efficient composites that originated from chitosan or other bio
      sorbents for environmental remediation.

PMID- 24910909
TI  - Thermo-mechanical properties and microfabric of fly ash-stabilized gold tailings.
AB  - This paper studies the changes in thermal conductivity, temperature, and
      unconfined compressive strength of gold tailings and fly ash mixtures during the
      curing period of 5 days. The microfabric of the cured mixtures was investigated
      with mercury intrusion porosimetry (MIP). The mixture samples were prepared at
      their maximum dry unit weight and optimum moisture content. Effect of adding fly
      ash to gold tailings (i.e., 0, 20, and 40% of the dry weight of tailings) was
      examined, and a comparison was made on samples prepared at the same fly ash
      content by replacing gold tailings with humic acid (i.e., gold tailings and humic
      acid ratios of 100:0, 90:10, and 80:20 by weight) or by varying pore fluid
      chemistry (i.e., water and salt solutions of 1M NaCl and CaCl2). The results show
      that the initial thermal conductivity of the samples is sensitive to the mixture
      proportion and a declination in the thermal conductivity is observed due to
      hydration of fly ash and evaporation. Inclusion of fly ash and salts into gold
      tailings improves the unconfined compressive strength but the presence of humic
      acid in samples leads to the decrease of the strength. MIP results reveal the
      pore structure changes associated with the packing states of the samples that
      reflect the influential factors considered. 

PMID- 24910910
TI  - Aquatic toxicity of dyes before and after photo-Fenton treatment.
AB  - This study evaluated the ecotoxicity of five dyes to freshwater organisms before
      and during their photo-Fenton degradation. EC50 (48h) of the five tested dyes
      ranged from of 6.9 to >1000mgL(-1) for Daphnia similis. In the chronic tests IC50
      (72h) varied from 65 to >100mgL(-1) for Pseudokirchneriella subcapitata and IC50
      (8 days) from 0.5 to 410mgL(-1) for Ceriodaphnia dubia. Toxicity tests revealed
      that although the applied treatment was effective for decolorization of the dye,
      the partial mineralization may be responsible for the presence of degradation
      products which can be either more toxic than the original dye, as is the case of
      Vat Green 3 and Reactive Black 5, lead to initially toxic products which may be
      further degraded to non toxic products (acid Orange 7 and Food Red 17), or
      generate non toxic products as in the case of Food Yellow 3. The results
      highlighted the importance of assessing both acute and chronic toxicity tests of
      treated sample before effluent discharge. 

PMID- 24910911
TI  - Adsorption of antimony onto iron oxyhydroxides: adsorption behavior and surface
      structure.
AB  - Antimony is detected in soil and water with elevated concentration due to a
      variety of industrial applications and mining activities. Though antimony is
      classified as a pollutant of priority interest by the United States Environmental
      Protection Agency (USEPA) and Europe Union (EU), very little is known about its
      environmental behavior and adsorption mechanism. In this study, the adsorption
      behaviors and surface structure of antimony (III/V) on iron oxides were
      investigated using batch adsorption techniques, surface complexation modeling
      (SCM), X-ray photon spectroscopy (XPS) and extended X-ray absorption fine
      structure spectroscopy (EXAFS). The adsorption isotherms and edges indicated that
      the affinity of Sb(V) and Sb(III) toward the iron oxides depended on the Sb
      species, solution pH, and the characteristics of iron oxides. Sb(V) adsorption
      was favored at acidic pH and decreased dramatically with increasing pH, while
      Sb(III) adsorption was constant over a broad pH range. When pH is higher than 7,
      Sb(III) adsorption by goethite and hydrous ferric oxide (HFO) was greater than
      Sb(V). EXAFS analysis indicated that the majority of Sb(III), either adsorbed
      onto HFO or co-precipitated by FeCl3, was oxidized into Sb(V) probably due to the
      involvement of O2 in the long duration of sample preservation. Only one Sb-Fe
      subshell was filtered in the EXAFS spectra of antimony adsorption onto HFO, with
      the coordination number of 1.0-1.9 attributed to bidentate mononuclear edge
      sharing ((2)E) between Sb and HFO. 

PMID- 24910912
TI  - Earthworm eco-physiological characteristics and quantification of earthworm
      feeding in vermifiltration system for sewage sludge stabilization using stable
      isotopic natural abundance.
AB  - Previous studies showed that the presence of earthworm improves treatment
      performance of vermifilter (VF) for sewage sludge stabilization, but earthworm
      eco-physiological characteristics and effects in VF were not fully investigated.
      In this study, earthworm population, enzymatic activity, gut microbial community
      and stable isotopic abundance were investigated in the VF. Results showed that
      biomass, average weight, number and alkaline phosphatase activity of the
      earthworms tended to decrease, while protein content and activities of peroxidase
      and catalase had an increasing tendency as the VF depth. Earthworm gut microbial
      communities were dominated by Gammaproteobacteria, and the percentages arrived to
      76-92% of the microbial species detected. (15)N and (13)C natural abundance of
      the earthworms decreased with operation time, and increased as the VF depth.
      Quantitative analysis using delta(15)N showed that earthworm feeding and
      earthworm-microorganism interaction were responsible for approximately 21% and
      79%, respectively, of the enhanced volatile suspended solid reduction due to the
      presence of earthworm. The finding provides a quantitative insight into how
      earthworms influence on sewage sludge stabilization in vermifiltration system. 

PMID- 24910913
TI  - Simultaneous removal of NOx and SO2 from flue gas using combined Na2SO3 assisted
      electrochemical reduction and direct electrochemical reduction.
AB  - A method combining Na2SO3 assisted electrochemical reduction and direct
      electrochemical reduction using Fe(II)(EDTA) solution was proposed to
      simultaneously remove NOx and SO2 from flue gas. Activated carbon was used as
      catalyst to accelerate the process. This new system features (a) direct
      conversion of NOx and SO2 to harmless N2 and SO4(2-); (b) fast regeneration of
      Fe(II)(EDTA); (c) minimum use of chemical reagents; and (d) recovery of the
      reduction by-product (Na2SO4). Fe(II)(EDTA) solution was continuously recycled
      and reused during entire process, and no harmful waste was generated.
      Approximately 99% NOx and 98% SO2 were removed under the optimal condition. The
      stability test showed that the system operation was reliable. 

PMID- 24910914
TI  - Preterm premature rupture of membranes in singleton vs twin pregnancies: The
      latency periods and the clinical outcomes revisited.
AB  - Our objective was to compare the latency periods after preterm premature rupture
      of membranes (PPROM) and determine its subsequent impact on maternal and fetal
      outcomes for singleton and twin gestations > 24 weeks' and <= 34 weeks'
      gestation. Delivery in the first 72 h after the rupture of membranes was observed
      to be more frequent in the twin group (RR 1.98, 95% CI 1.06-3.73, p = 0.03);
      whereas the overall median latency periods were comparable (p = 0.06). Singleton
      pregnancies had shorter latency periods after 28 gestational weeks by comparison
      to the latency periods before 28 weeks. Gestational age of rupture of membranes
      and delivery and latency periods were comparable between spontaneous twin
      pregnancies and twin pregnancies after assisted reproductive technologies (ART).
      As a conclusion, singleton and twin pregnancies had similar outcomes after PPROM.
      The first 72 h is especially important for the outcome of twin pregnancies at
      when the delivery risk is high.

PMID- 24910915
TI  - Advances in mixed-integer programming methods for chemical production scheduling.
AB  - The goal of this paper is to critically review advances in the area of chemical
      production scheduling over the past three decades and then present two recently
      proposed solution methods that have led to dramatic computational enhancements.
      First, we present a general framework and problem classification and discuss
      modeling and solution methods with an emphasis on mixed-integer programming (MIP)
      techniques. Second, we present two solution methods: (a) a constraint propagation
      algorithm that allows us to compute parameters that are then used to tighten MIP
      scheduling models and (b) a reformulation that introduces new variables, thus
      leading to effective branching. We also present computational results and an
      example illustrating how these methods are implemented, as well as the resulting
      enhancements. We close with a discussion of open research challenges and future
      research directions. 

PMID- 24910916
TI  - Factors affecting the rheology and processability of highly filled suspensions.
AB  - Suspensions filled with rigid particles at volume-loading levels that approach
      their maximum packing fraction are widely encountered, especially in the
      energetics, ceramics, pharmaceutical, magnetics, composites, food, and personal
      care industries. Highly filled suspensions, regardless of industrial application,
      exhibit a number of common rheological and processability traits, including
      viscoplasticity and wall slip, that necessitate special rheometers and
      appropriate characterization and numerical simulation methods. Furthermore,
      various factors, including the dispersion and distribution of the particles and
      their agglomerates, the entrainment of air, the filtration-based migration of the
      binder phase, and the shear-induced migration of particles, play important roles
      and must be considered in the design and optimization of manufacturing operations
      for processing of highly filled suspensions. 

PMID- 24910918
TI  - Biocatalysts for natural product biosynthesis.
AB  - Natural products are important sources of pharmaceuticals, in part owing to their
      diverse biological activities. Enzymes from natural product biosynthetic pathways
      have become attractive candidates as biocatalysts for modifying the structures
      and bioactivities of these complex compounds. Numerous enzymes have been
      harvested to generate innovative scaffolds, large-scale synthesis of chiral
      building blocks, and semisynthesis of medicinally relevant natural product
      derivatives. This review discusses recent examples from three areas: (a)
      polyketide catalytic domain engineering geared toward synthesis of new
      polyketides, (b) engineering of tailoring enzymes (other than oxidative enzymes)
      as biocatalysts, and (c) in vitro total synthesis of natural products using
      purified enzyme components. With the availability of exponentially increasing
      genomic information and new genome mining tools, many new and powerful
      biocatalysts tailored for pharmaceutical synthesis will likely emerge from
      secondary metabolism. 

PMID- 24910920
TI  - Ionic liquids in pharmaceutical applications.
AB  - In the past several years, ionic liquids (ILs) have been at the cutting edge of
      the most promising science and technology. ILs not only have found applications
      in classical areas of knowledge but also are important candidates to solve
      classical problems within several societal challenges, such as clean and
      efficient energy, through the development of a broad swath of energy
      technologies, such as advanced batteries, dye-sensitized solar cells, double
      layer capacitors, actuators, fuel cells, thermo-cells, and water splitting,
      essentially related to highly efficient carbon capture and storage technologies
      and resource efficiency to date. This review focuses on the application of IL
      methodologies to solve critical pharmaceutical problems, in particular, the low
      solubility and thus bioavailability of pharmaceutical compounds and the presence
      of polymorphs, which severely hamper the efficacy of important commercially
      available drugs. The development of strategies to use ILs as carriers of
      pharmaceutical active compounds is an extremely promising and wide avenue.
      Further, the synthesis of liquid salts through the discerning combination of
      cations and anions with several distinct pharmaceutical roles provides answers to
      some of today's pharmaceutical industrial challenges. 

PMID- 24910921
TI  - Perspectives on sustainable waste management.
AB  - Sustainable waste management is a goal that all societies must strive to
      maintain. Currently nearly 80% of global wastes are sent to landfill, with a
      significant amount lacking proper design or containment. The increased attention
      to environmental impacts of human activities and the increasing demand for energy
      and materials have resulted in a new perspective on waste streams. Use of waste
      streams for energy and materials recovery is becoming more prevalent, especially
      in developed regions of the world, such as Europe, the United States, and Japan.
      Although currently these efforts have a small impact on waste disposal, use of
      waste streams to extract value very likely will increase as society becomes more
      aware of the options available. This review presents an overview of waste
      management with a focus on following an expanded waste hierarchy to extract value
      specifically from municipal solid waste streams. 

PMID- 24910922
TI  - Experimental and theoretical methods in kinetic studies of heterogeneously
      catalyzed reactions.
AB  - This review aims to illustrate the potential of kinetic analysis in general and
      microkinetic modeling in particular for rational catalyst design. Both ab initio
      calculations and experiments providing intrinsic kinetic data allow us to assess
      the effects of catalytic properties and reaction conditions on the activity and
      selectivity of the targeted reactions. Three complementary approaches for kinetic
      analysis of complex reaction networks are illustrated, using select examples of
      acid zeolite-catalyzed reactions from the authors' recent work. Challenges for
      future research aimed at defining targets for synthesis strategies that enable us
      to tune zeolite properties are identified. 

PMID- 24910917
TI  - From stealthy polymersomes and filomicelles to "self" Peptide-nanoparticles for
      cancer therapy.
AB  - Polymersome vesicles and wormlike filomicelles self-assembled with amphiphilic,
      degradable block copolymers have recently shown promise in application to cancer
      therapy. In the case of filomicelles, dense, hydrophilic brushes of poly(ethylene
      glycol) on these nanoparticles combine with flexibility to nonspecifically delay
      clearance by phagocytes in vivo, which has motivated the development of "self"
      peptides that inhibit nanoparticle clearance through specific interactions.
      Delayed clearance, as well as robustness of polymer assemblies, opens the dosage
      window for delivery of increased drug loads in the polymer assemblies and
      increased tumor accumulation of drug(s). Antibody-targeting and combination
      therapies, such as with radiotherapy, are emerging in preclinical animal models
      of cancer. Such efforts are expected to combine with further advances in polymer
      composition, structure, and protein/peptide functionalization to further enhance
      transport through the circulation and permeation into disease sites. 

PMID- 24910919
TI  - A new toolbox for assessing single cells.
AB  - Unprecedented access to the biology of single cells is now feasible, enabled by
      recent technological advancements that allow us to manipulate and measure sparse
      samples and achieve a new level of resolution in space and time. This review
      focuses on advances in tools to study single cells for specific areas of biology.
      We examine both mature and nascent techniques to study single cells at the
      genomics, transcriptomics, and proteomics level. In addition, we provide an
      overview of tools that are well suited for following biological responses to
      defined perturbations with single-cell resolution. Techniques to analyze and
      manipulate single cells through soluble and chemical ligands, the
      microenvironment, and cell-cell interactions are provided. For each of these
      topics, we highlight the biological motivation, applications, methods, recent
      advances, and opportunities for improvement. The toolbox presented in this review
      can function as a starting point for the design of single-cell experiments. 

PMID- 24910923
TI  - Acid-responsive fluorescent compounds based on nitro-group-substituted L-shaped
      pentacycles, pyrrolo[1,2-a][1,8]naphthylidines.
AB  - Acid-responsive fluorescent compounds were prepared by introducing a nitrophenyl
      group to L-shaped pentacycles with a pyrrolo[1,2-a][1,8]naphthylidine backbone.
      These compounds show almost no fluorescence under neutral conditions, but emit
      green to orange fluorescence upon addition of trifluoroacetic acid. Acid
      titration experiments and NMR spectroscopy, plus DFT calculations, show that
      formation of a pyridinium cation species is responsible for the appearance of
      fluorescence. 

PMID- 24910924
TI  - Successful treatment with infliximab of sibling cases with generalized pustular
      psoriasis caused by deficiency of interleukin-36 receptor antagonist.

PMID- 24910926
TI  - Longitudinal assessment of the effect of age and experience on performance in 161
      km ultramarathons.
AB  - PURPOSE: This work longitudinally assesses the influence of aging and experience
      on time to complete 161-km ultramarathons. METHODS: From 29,331 finishes by 4066
      runners who had completed 3 or more 161-km ultramarathons in North America from
      1974 through 2010, independent cohorts of men (n = 3,092), women (n = 717), and
      top-performing men (n = 257) based on age-group finish place were identified.
      Linear mixed-effects regression was used to assess the effects of aging and
      previous 161-km finish number on finish time adjusted for the random effects of
      runner, event, and year. RESULTS: Men and women up to 38 y of age slowed by 0.05
      0.06 h/y with advancing age. Men slowed 0.17 h/y from 38 through 50 y and 0.23
      h/y after 50 y. Women slowed 0.20-0.23 h/y with advancing age from 38 y. Top
      performing men under 38 y did not slow with increasing age but slowed by 0.26 and
      0.39 h/y from 38 through 50 y and after 50 y, respectively. Finish number was
      inversely associated with finish time for all 3 cohorts. A 10th or higher finish
      was 1.3, 1.7, and almost 3 h faster than a first finish for men, women, and top
      performing men, respectively. CONCLUSIONS: High-level performances in 161-km
      ultramarathoners can be sustained late into the 4th decade of life, but
      subsequent aging is associated with declines in performance. Nevertheless, the
      adverse effects of aging on performance can be offset by greater experience in
      these events.

PMID- 24910925
TI  - Effect of UGT1A1, UGT1A3, DIO1 and DIO2 polymorphisms on L-thyroxine doses
      required for TSH suppression in patients with differentiated thyroid cancer.
AB  - AIM: To evaluate the impact of genetic polymorphisms in uridine 5'
      glucuronosylytansferases UGT1A1 and UGT1A3 and iodothyronine-deiodinases types 1
      and 2 on levothyroxine (T4 ; 3,5,3',5'-triiodo-L-thyronine) dose requirement for
      suppression of thyrotropin (TSH) secretion in patients with differentiated
      thyroid cancer (DTC). METHODS: Patients (n = 268) submitted to total
      thyroidectomy and ablation by (131) I, under T4 therapy for at least 6 months
      were recruited in three public institutions in Brazil. Multivariate regression
      modelling was applied to assess the association of T4 dosing with polymorphisms
      in UGT1A1 (rs8175347), UGT1A3 (rs3806596 and rs1983023), DIO1 (rs11206244 and
      rs2235544) and DIO2 (rs225014 and rs12885300), demographic and clinical
      variables. RESULTS: A regression model including UGT1A haplotypes, age, gender,
      body weight and serum TSH concentration accounted for 39% of the inter-individual
      variation in the T4 dosage. The association of T4 dose with UGT1A haplotype is
      attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of
      carriers of low expression UGT1A1 rs8175347 alleles. The DIO1 and DIO2 genotypes
      had no influence of T4 dosage. CONCLUSION: UGT1A haplotypes associate with T4
      dosage in DTC patients, but the effect accounts for only 2% of the total
      variability and recommendation of pre-emptive UGT1A genotyping is not warranted.

PMID- 24910927
TI  - Wee1 and Cdc25 control morphogenesis, virulence and multistress tolerance of
      Beauveria bassiana by balancing cell cycle-required cyclin-dependent kinase 1
      activity.
AB  - Modification of cell cycle in entomopathogenic fungi is likely crucial for host
      infection and environmental adaptation. Here we show that Wee1 and Cdc25 can
      balance cell cycle-required cyclin-dependent kinase 1 (Cdk1) activity in
      Beauveria bassiana. The Cdk1 phosporylation signal was strong in Deltacdc25 but
      very weak in Deltawee1 and absent in Deltawee1Deltacdc25. Consequently, cell
      cycles, septation patterns and many septation-dependent gene transcripts of these
      mutants were reversely changed. Hyphal cells were short in Deltawee1, slender in
      Deltacdc25 and short and swollen in Deltawee1Deltacdc25. Conidiation was most
      defective in Deltawee1, followed by Deltacdc25. Their conidia and yeast-like
      blastospores also altered antagonistically in both size and complexity,
      accompanied with abnormally branched germlings in Deltawee1 and
      Deltawee1Deltacdc25. Conidial thermotolerance and UV-B resistance decreased much
      more in Deltawee1Deltacdc25 than in Deltawee1 but significantly increased in
      Deltacdc25. The double deletion and the point mutation Cdk1(T14A/P15F) for
      inhibitory phosphorylation caused most defective virulence, followed by wee1
      deletion. All the changes were restored by ectopic gene complementation.
      Virulence changes in all the mutants and control strains were highly correlated
      to those in blastospore size or complexity. Taken together, Wee1 and Cdc25
      control cell cycle, morphogenesis, asexual development, stress tolerance and
      virulence of B. bassiana by balancing the Cdk1 activity. 

PMID- 24910929
TI  - Comparison of mirror, raw video, and real-time visual biofeedback for training
      toe-out gait in individuals with knee osteoarthritis.
AB  - OBJECTIVE: To compare performance error and perceived difficulty during toe-out
      gait modification in people with knee osteoarthritis (OA) across 3 different
      types of visual feedback: mirror, raw video, and real-time biofeedback of toe-out
      angle. DESIGN: Repeated-measures, within-subject trial. SETTING: University
      motion analysis laboratory. PARTICIPANTS: Individuals with knee OA (N=20; 11
      women; mean age, 65.4+/-9.8y) participated in this study. Seven participants had
      mild knee OA, 9 had moderate knee OA, and 4 had severe knee OA. INTERVENTIONS:
      Participants were trained to walk on a treadmill while matching a target
      indicating a 10 degrees  increase in stance phase toe-out compared with toe-out
      angle measured during self-selected walking. The target was provided visually via
      the 3 types of feedback listed above and were presented in a random order. MAIN
      OUTCOME MEASURES: Kinematic data were collected and used to calculate the
      difference between the target angle and the actual performed angle for each
      condition (toe-out performance error). Difficulty was assessed using a numerical
      rating scale (0-10) provided verbally by participants. RESULTS: Toe-out
      performance error was significantly less when using the real-time biofeedback
      method than when using the other 2 methods (P=.025; mean difference vs
      mirror=2.05 degrees ; mean difference vs raw video=1.51 degrees ). Perceived
      difficulty was not statistically different between the groups (P=.51).
      CONCLUSIONS: Although statistically significant, the 2 degrees  difference in toe
      out gait performance error may not necessitate the large economic and personnel
      costs of real-time biofeedback as a means to modify movement in clinical or
      research settings.

PMID- 24910930
TI  - Structure and supersaturation of highly concentrated solutions of buckyball in 1
      butyl-3-methylimidazolium tetrafluoroborate.
AB  - Solubilization of fullerenes is of high interest because of their wide usage in
      both fundamental research and numerous applications. This paper reports molecular
      dynamics (MD) simulations of saturated and supersaturated solutions of C60 in 1
      butyl-3-methylimidazolium tetrafluoroborate, [C4C1IM][BF4], room-temperature
      ionic liquid (RTIL). The simulations cover a wide range of temperatures between
      280 and 500 K at ambient pressure. Unlike in simpler solvents, C60 in
      [C4C1IM][BF4] forms highly supersaturated solutions, whose internal arrangement
      remains unaltered during nearly a microsecond-long real-time dynamics. The ion
      molecular structure patterns in saturated and supersaturated solutions are
      distinguished in terms of radial distribution functions and cluster analysis of
      the solute particles. The cation separated solute pair is found to be a common
      structure in both saturated and supersaturated solutions. This observation
      suggests that the imidazolium cation plays an important role in the successful
      dispersion of C60 molecules. Anticipated practical applications of the observed
      phenomenon are briefly discussed. 

PMID- 24910928
TI  - Menopausal hormone therapy and cancer: changing clinical observations of target
      site specificity.
AB  - Menopausal hormone therapy with estrogen plus progestin or estrogen alone (for
      women with prior hysterectomy) is still used by millions of women for climacteric
      symptom management throughout the world. Until 2002, hormone therapy influence on
      cancer risk and other chronic diseases was determined through observational study
      reports. Since then, results from the Women's Health Initiative randomized,
      placebo-controlled hormone therapy trials have substantially changed concepts
      regarding estrogen plus progestin and estrogen alone influence on the most common
      cancers in postmenopausal women. In these trials, estrogen plus progestin
      significantly increased breast cancer incidence and deaths from breast cancer,
      significantly increased deaths from lung cancer, significantly decreased
      endometrial cancer, and did not have a clinically significant influence on
      colorectal cancer. In contrast, estrogen alone use in women with prior
      hysterectomy significantly reduced breast cancer incidence and deaths from breast
      cancer without significant influence on colorectal cancer or lung cancer. These
      complex results are discussed in the context of known potential mediating
      mechanisms of action involved in interaction with steroid hormone receptors. 

PMID- 24910931
TI  - Cerebrospinal fluid shunt infection caused by Corynebacterium sp: case report and
      review.
AB  - BACKGROUND: A 36-year-old immunocompetent woman with a posterior fossa
      arteriovenous malformation (PF-AVM) and hydrocephalus presented with low fever
      and mental confusion 4 days after ventriculoperitoneal shunting (VPS). METHODS:
      Cerebrospinal fluid (CSF) and ventricular catheter tip cultures isolated
      Corynebacterium sp. Similar to previous cases in the literature, species
      determination was not possible. However, the antibiotic sensitivity profile of
      this isolate suggested Corynebacterium jeikeium. Conversion to external
      ventricular drainage (EVD) was done and intravenous vancomycin was administered
      for 21 days. RESULTS AND CONCLUSIONS: The patient showed progressive improvement.
      Since the first CSF shunt infection caused by Corynebacterium sp., 16 other cases
      in the literatures have been reported. Additionally, this study reports the
      difficulties in recognizing CSF shunt infection caused by this agent and the
      possible clinical or laboratory patterns as observed in the literature.

PMID- 24910932
TI  - Case report: diagnosis and management of peritoneovaginal fistula.
AB  - Fallopian tube vaginal fistula, a form of peritoneovaginal fistula, is an
      uncommon cause of persistent vaginal leakage after hysterectomy. Fallopian tube
      vaginal fistula resulting in peritoneal leakage has been reported in conjunction
      with a prolapsed fimbria. Herein is presented a case of fallopian tube vaginal
      fistula without a visibly prolapsed tubal fimbria. The patient was a 43-year-old
      woman with a 6-year history of cyclic vaginal leakage with onset shortly after
      vaginal hysterectomy. Examination using a vaginal speculum revealed a clear
      vaginal fluid but no distinct lesion or mass in the vagina, and bimanual
      examination did not reveal a vesicovaginal or ureterovaginal fistula.
      Laparoscopic surgical exploration revealed a densely adherent fallopian tube
      attached to the vaginal cuff, forming a fallopian tube vaginal fistula. 

PMID- 24910933
TI  - Contrast ultrasonography for tubal patency.
AB  - Evaluation of tubal patency is an essential part of a fertility workup.
      Laparoscopy with chromopertubation in conjunction with hysteroscopy is the gold
      standard in evaluation of tubal patency and the uterine cavity. In this review
      article we describe a newer method for evaluation of the uterus and fallopian
      tubes, that is, hysterosalpingo-contrast sonography (HyCoSy). Accuracy of HyCoSy
      for tubal patency has been shown to be comparable to that with
      hysterosalpingography (HSG) when compared with laparoscopic chromopertubation.
      Sensitivity ranges from 75% to 96%, and specificity from 67% to 100%. HyCoSy is
      also accurate when compared with HSG in determining tubal occlusion after
      hysteroscopic sterilization, with 88% of patients stating they would prefer to
      undergo the tubal occlusion test in their gynecologist's office. Because HyCoSy
      also includes evaluation of the uterine cavity with saline solution-enhanced
      sonohysterography, accuracy in evaluating the uterine cavity is >90% when
      compared with hysteroscopy. HyCoSy enables the gynecologist to complete a
      fertility workup in the office in the most minimally invasive way. HyCoSy is well
      tolerated and has been suggested in the literature to replace HSG for evaluation
      of tubal disease in the subfertile population.

PMID- 24910934
TI  - Treatment of major depressive disorder using botulinum toxin A: a 24-week
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To determine whether a single treatment of botulinum toxin A in the
      forehead (glabellar) region can improve symptoms of depression in patients with
      major depressive disorder (MDD), as defined by DSM-IV criteria. METHOD: Thirty
      participants were randomly assigned to receive either placebo or botulinum toxin
      A (BTA; onabotulinumtoxinA) injections in the forehead. Female participants
      received 29 units; male participants received 39 units. At week 12, the groups
      were crossed over. Participants were evaluated at weeks 0, 3, 6, 12, 15, 18, and
      24 for improvement in MDD symptoms using the Patient Health Care Questionnaire-9,
      Beck Depression Inventory (BDI), and 21-Item Hamilton Depression Rating Scale
      (HDRS-21) objective measurement scales. The primary outcome was the rate of HDRS
      21 response, defined as >= 50% score reduction from baseline. The study occurred
      from July 2011 to November 2012. RESULTS: Patients who received BTA at week 0
      (BTA-first group) and at week 12 (BTA-second group) had a statistically
      significant reduction in MDD symptoms as compared to placebo. Improvement in MDD
      continued over 24 weeks in the group that received BTA first even though the
      cosmetic effects of BTA wore off at 12 to 16 weeks. HDRS-21 response rates were
      55% (6/11) in the BTA-first group, 24% (4/17) in the BTA-second group, and 0%
      (0/19) in the placebo group (P < .0001). HDRS-21 remission rates (score <= 7)
      were 18% (2/11), 18% (3/17), and 0% (0/19), respectively (P = .057). HDRS-21
      scores dropped -46% and -35% in the BTA-first and -second groups versus -2% in
      the placebo group (P < .0001). The BDI response rate (>= 50% reduction from
      baseline) was 45% (5/11) in the BTA-first group, 33% (6/18) in the BTA-second
      group, and 5% (1/19) in the placebo group (P = .0067). BDI remission rates (score
      <= 9) were 27% (3/11), 33% (6/18), and 5% (1/19), respectively (P = .09). BDI
      scores dropped -42% and -35% in the BTA-first and -second groups versus -15% in
      the placebo group (P < .0001). CONCLUSIONS: Botulinum toxin A injection in the
      glabellar region was associated with significant improvement in depressive
      symptoms and may be a safe and sustainable intervention in the treatment of MDD.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01392963.

PMID- 24910935
TI  - Guidewire-assisted transpancreatic sphincterotomy for difficult biliary
      cannulation: a prospective randomized controlled trial.
AB  - PURPOSE: Precut techniques have been used to facilitate biliary cannulation
      during difficult endoscopic retrograde cholangiopancreatography. Presently,
      needle-knife sphincterotomy (NKS) is a commonly used precut technique. Since its
      first description, transpancreatic sphincterotomy, as an alternative method for
      bile duct entry when conventional biliary cannulation failed, has been debated on
      its success rate of cannulation and its complications, such as increased
      incidence of pancreatitis. Guidewire techniques are another effective method to
      improve the success rate of selective bile duct cannulation. This is a single
      center prospective randomized controlled trial aimed to compare success rate,
      cannulation time, and complications of guidewire-assisted transpancreatic
      sphincterotomy (GATS) and NKS for difficult biliary cannulation. METHODS: Between
      July 2010 and October 2013, consecutive patients who failed in the standard
      biliary cannulation were randomly assigned to the GATS and NKS groups. The
      outcome measures included success rate, cannulation time, and complications.
      RESULTS: A total of 149 patients were enrolled and analyzed: 73 in the GATS group
      and 79 in the NKS group. The characteristics of the 2 groups were similar. Bile
      duct cannulation was successful in 70 patients (95.9%) in the GATS group and 64
      (84.2%) in the NKS group (P=0.018). The median cannulation time spent in precut
      was 193 seconds in the GATS group and 485 seconds in the NKS group (P<0.001).
      There was no difference between the groups for the incidence of complications,
      pancreatitis, and hemorrhage (9.6% vs. 10.5%, 6.8% vs. 6.6%, 1.4% vs. 3.9%,
      respectively). No perforation occurred. CONCLUSIONS: GATS compared with NKS
      increases biliary cannulation rate and requires less cannulation time during
      difficult biliary access. This technique is not associated with an increased risk
      for complications. It seems to be an effective and safe alternative for biliary
      access during difficult endoscopic retrograde cholangiopancreatography.

PMID- 24910936
TI  - Appendectomy in women. Is the laparoscopic approach always better than the "open"
      approach in uncomplicated appendicitis?
AB  - BACKGROUND: Acute appendicitis is the most common emergency in abdominal surgery,
      but remains a continuing controversy regarding the most appropriate method of
      removing the inflamed appendix. MATERIALS AND METHODS: From January 2002 to
      December 2012, 1037 women underwent appendectomy (average age: 25+/-15.7 y;
      range: 6 to 91 y). Of these, 519 underwent open appendectomy (OA) and 518
      underwent laparoscopic appendectomy (LA). For all the patients we determined the
      postoperative hospital stay, the eventual readmissions within 30 days after
      discharge, the length of surgical procedures (data were available only for the
      period from January 2008 to December 2012), the costs for the OA and LA, and the
      rate of negative appendicitis. RESULTS: In our cohort of patients, 189 women
      (18.2%) had a negative appendectomy. Considering the postoperative hospital stay
      (average: 4.2+/-3.6 d; range: 1 to 32 d in OA group and average: 3.9+/-3.1 d;
      range: 1 to 21 d in LA group; P=0.15) there were no statistical differences
      between 2 groups. The average length of surgical procedures in LA group was
      42.3+/-18.4 minutes (range: 8 to 135 min) and 43.2+/-19 minutes in the OA group
      (range: 10 to 135 min) (P=0.63). The average net cost of LA was 1203.61 euros,
      whereas for OA it was 95.18 euros. In this study, we considered only the surgical
      materials. CONCLUSIONS: LAs are not associated with a lower complication rate
      than the OAs and, above all, LAs are more expensive than OAs. Also we believe
      that laparoscopic approach should be used only in case of unclear abdominal pain
      and not for the treatment of clear acute and uncomplicated appendicitis.

PMID- 24910937
TI  - The role of staging laparoscopy in treatment of locally advanced gastric cancer.
AB  - PURPOSE: The aim of this study was to evaluate the role of videolaparoscopy (VLP)
      in gastric cancer staging, particularly for the detection of peritoneal cancer,
      to verify its impact in changing the therapeutic conduct, as well as defining the
      characteristics of the group that can benefit from VLP as staging method.
      PATIENTS AND METHODS: A prospective cohort study was conducted from May 2011 to
      March 2013. Thirty-two patients with gastric adenocarcinoma underwent
      conventional staging together with VLP staging. RESULTS: VLP identified
      peritoneal disease in 22.6% of patients. Sensitivity was 86%, and specificity was
      100%. In the group with non-Borrmann IV, <8 cm tumors, and without evidence of
      lymphadenomegaly, VLP identified peritoneal implants in 23.1% of cases.
      CONCLUSIONS: VLP is a safe procedure capable of improving the accuracy of gastric
      cancer staging. There is no justification for failing to perform laparoscopy in
      patients with <8 cm, non-Borrmann type IV tumors and without evidence of
      lymphadenomegaly on preoperative examinations.

PMID- 24910938
TI  - Admission levels of serum amyloid a and procalcitonin are more predictive of the
      diagnosis of acute appendicitis compared with C-reactive protein.
AB  - BACKGROUND: Acute appendicitis is the commonest surgical emergency, but its
      diagnosis can be elusive with a negative appendicectomy rate of 20%. The aims of
      this study were to investigate the potential value of the markers of acute
      inflammation, serum amyloid A (SAA), and serum procalcitonin (ProCT), in the
      diagnosis of acute appendicitis in adults and to compare that with the commonly
      used serum C-reactive protein (CRP). METHODS: Adult patients presenting with
      acute right lower abdominal pain and a clinical suspicion of acute appendicitis
      were included. Blood samples were obtained within 6 hours of admission for rapid
      serum CRP assay and for end-of-recruitment batch analysis of SAA and serum ProCT
      concentrations. RESULTS: A total of 147 patients (81 males) with a mean (+/-SD)
      age of 36 (+/-17) years were recruited. Appendicitis was confirmed histologically
      in 61 of 72 patients (84.7%) who underwent appendicectomy. A post hoc analysis
      revealed a diagnostic sensitivity and specificity for SAA of 92% and 72%, ProCT
      of 85% and 74%, and CRP of 75% and 72%, respectively. The receiver operator
      characteristics for the area under the curves showed that SAA (P=0.011) and ProCT
      (P=0.037) significantly exceeded CRP in the prediction of acute appendicitis on
      admission. CONCLUSIONS: The measurement of SAA and serum ProCT on admission in
      patients with clinically suspected acute appendicitis seems to outperform serum
      CRP in aiding that diagnosis.

PMID- 24910939
TI  - Single-port laparoscopic left adrenalectomy (SILS): 3 years' experience of a
      single institution.
AB  - BACKGROUND: Laparoscopic adrenalectomy by 3 or 4 trocars is a well-established
      procedure. This report describes the initial experience with single-incision
      laparoscopic surgery (SILS) using the transperitoneal approach for left
      adrenalectomy. METHODS: Between April 2010 and January 2013, all consecutive
      patients with adrenal masses who agreed to undergo SILS adrenalectomy were
      included in a prospective study. The left 2.5 cm subcostal incision was the sole
      point of entry. Data of patients undergoing SILS adrenalectomy were compared with
      those from an uncontrolled group of patients undergoing conventional laparoscopic
      adrenalectomy during the same study period. RESULTS: There were 40 patients in
      each study group. SILS was successfully performed and none of the patients
      required conversion to an open procedure. In 1 case of SILS procedure, an
      additional lateral 5 mm port was needed for retraction of the kidney. The mean
      (SD) duration of the operation was 80 (20) minutes in the SILS group and 75 (8)
      minutes in the conventional laparoscopic adrenalectomy group (P=0.150). No
      intraoperative or postoperative complications occurred. Differences between the 2
      study groups in postoperative pain, number of patients resuming oral intake
      within the first 24 hours, final pathologic diagnosis (Conn syndrome, Cushing
      adenomas, nonfunctioning adrenal tumors), and length of hospital stay were not
      observed. CONCLUSIONS: SILS left adrenalectomy is a technically feasible and safe
      procedure in carefully selected patients and seems to have results similar to a
      conventional approach in our initial comparison.

PMID- 24910940
TI  - Recurrent inguinal hernia repair: what is the evidence of case series? A meta
      analysis and metaregression analysis.
AB  - To examine, if case series considered together with observational studies tend to
      produce similar results as randomized-controlled trials (RCTs), on recurrent
      hernia repair. A systematic literature review and meta-analysis between 1990 and
      2013 revealed 46 nonrandomized studies (NRCTs) and 5 RCTs including 25,730
      patients. A direct comparison of the summary estimates between RCTs and NRCTs is
      presented. Outcomes, within or across studies, were compared. Comparisons of all
      outcomes in NRCTs and RCTs failed to show statistical significance.
      Prospective/retrospective cohort studies, case series, and RCTs did not differ
      significantly in their estimates. Adjusted testing for metaregression disclosed
      that rerecurrence among NRCTs was independent of the study design. The number of
      included patients and study setting were independent predictors of outcome. Our
      proposed methodology for a systematic review could potentially give answers where
      level I evidence is missing or could be a tool for optimization of a RCT design. 

PMID- 24910941
TI  - Use of confocal laser endomicroscopy to assess the adequacy of endoscopic
      treatment of gastrointestinal neoplasia: a systematic review and meta-analysis.
AB  - Evaluation of the adequacy of endoscopic mucosal resection (EMR) of
      gastrointestinal lesions remains challenging by use of conventional endoscopy.
      Confocal laser endomicroscopy (CLE) is a novel imaging technique, designed to
      provide in vivo histology, and facilitate diagnosis with real-time intervention.
      We undertook a systematic review of the available literature, exploring the role
      of CLE in assuring completeness of EMR of gastrointestinal lesions. The number of
      pertinent studies is very limited, including only 1 randomized controlled study
      and 2 prospective comparative case series. Per-lesion meta-analysis showed that
      the sensitivity of CLE for detection of residual neoplasia was 91% (95%
      confidence interval, 82.5%-96%) with specificity of 69% (95% confidence interval,
      61%-77%), with significant heterogeneity noted in all outcomes. In conclusion,
      the evidence underpinning the usefulness of CLE in ensuring adequate EMR of
      gastrointestinal neoplasia is currently very weak, with limited promising results
      related to gastric and colorectal polyp resections. 

PMID- 24910942
TI  - Efficacy and safety of remifentanil and sulfentanyl in painless gastroscopic
      examination: a prospective study.
AB  - We aim to assess efficacy and safety of remifentanil or sulfentanyl combined with
      propofol during painless gastroscopic examination in patients. In this study, 270
      patients were randomly divided into 3 groups: propofol was given only in group P;
      propofol and remifentanil in group PR; propofol and sulfentanyl in group PS
      during the gastroscopic examination. Efficiency of group P was significantly
      higher than that of group PR and PS (P<0.01) [corrected]. Efficiency of group PR
      was lower than that of group PS (P<0.05). Incidence of chest wall rigidity and
      oxygen desaturation in group PR were higher than group P and PS (P<0.05), whereas
      there was no difference between groups P and PS (P>0.05). Propofol combined with
      remifentanil could provide satisfying anesthesia and more respiratory depression,
      whereas sulfentanyl at equivalent dose combined with propofol could also provide
      with satisfying anesthesia and less respiratory depression. Combined sufentanyl
      with propofol would be an effective anesthesia technique in the daytime
      procedure.

PMID- 24910943
TI  - Bromodeoxyuridine (BrdU) treatment to measure hepatocellular proliferation does
      not mask furan-induced gene expression changes in mouse liver.
AB  - Bromodeoxyuridine (BrdU) is a synthetic nucleoside used to detect cellular
      proliferation. BrdU incorporates in the place of thymine but pairs with guanine,
      thereby increasing the risk of transition mutations in dividing cells. Given its
      mutagenicity, standard practice is to use a second cohort of animals for parallel
      toxicogenomics studies; however, the impact of BrdU on global gene expression is
      unknown. To test this, we performed a case study to determine whether the
      molecular mode of action of furan, a liver carcinogen, could be detected in BrdU
      treated samples. We measure global hepatic gene expression using Agilent DNA
      microarrays in female B6C3F1 mice that were sub-chronically exposed to 0, 1, 4,
      or 8mg/kg bodyweight (bw) per day furan either in the presence (+BrdU) or absence
      (-BrdU) of BrdU. Exposure to 0.02% BrdU in drinking water for five days resulted
      in minimal gene expression changes. A comparison of +BrdU versus -BrdU control
      mice revealed only 11 probes with fold change>=1.5 and false discovery rate (FDR)
      corrected p<=0.05. The same comparison in the high dose group yielded only 3
      differentially expressed probes. Differentially expressed gene lists generated
      for furan-treated versus control mice and were compared for the -BrdU and +BrdU
      groups. The high dose of furan had 452 shared probes and 27 and 90 unique probes
      for -BrdU and +BrdU groups, respectively. These differences did not impact
      hierarchical clustering. Further, they did not impair detection of the previously
      reported furan mode of action, which was well represented in the BrdU-treated
      samples. Taken together, we demonstrate that BrdU treatment does not mask
      important furan-induced transcriptional changes. We suggest that BrdU-treated
      mice could be used for toxicogenomic analysis, which would generally halve the
      number of rodents required for toxicogenomics studies. However, we also recommend
      that this type of case study be repeated for other chemicals before the use of
      BrdU-treated animals in omics studies becomes common practice. 

PMID- 24910944
TI  - Essure(r) and chronic pelvic pain: a population-based cohort.
AB  - The aim of this study was to assess the incidence of chronic pelvic pain in women
      after placement of Essure(r) microinserts. This was a case series study at the
      hysteroscopy unit in a teaching hospital. We included 4,274 patients undergoing
      permanent sterilisation with Essure(r) microinserts from January 2005 to December
      2011. Essure devices were removed in all patients reporting pelvic pain after
      insertion. All data were collected from the hysteroscopy unit database with later
      review of medical records in cases of chronic pelvic pain and a telephone survey
      after microinsert removal. Main outcome measures were: grade of procedure
      difficulty perceived by the surgeon; tolerance described by the patient after
      placement; the need for analgesics during or immediately after the procedure;
      side-effects; average time between device placement and the onset of symptoms;
      time between device placement and removal; technique for device removal and any
      symptoms thereafter. A total of seven women (0.16%) presented with chronic pelvic
      pain requiring microinsert removal, with four classifying the pain perceived
      during the procedure as medium-high. Six patients did not require analgesics
      after the procedure and a vasovagal syndrome requiring intravenous analgesia and
      monitoring occurred in only one case. Six women reported pain immediately after
      the procedure, with a mean time between placement and removal of 29.4 months. In
      all cases, the symptoms disappeared after Essure removal. We conclude that the
      development of chronic pelvic pain is very uncommon after placement of Essure
      microinserts. Removal of these devices usually improves the pain.

PMID- 24910945
TI  - MOPED 2.5--an integrated multi-omics resource: multi-omics profiling expression
      database now includes transcriptomics data.
AB  - Multi-omics data-driven scientific discovery crucially rests on high-throughput
      technologies and data sharing. Currently, data are scattered across single omics
      repositories, stored in varying raw and processed formats, and are often
      accompanied by limited or no metadata. The Multi-Omics Profiling Expression
      Database (MOPED, http://moped.proteinspire.org ) version 2.5 is a freely
      accessible multi-omics expression database. Continual improvement and expansion
      of MOPED is driven by feedback from the Life Sciences Community. In order to meet
      the emergent need for an integrated multi-omics data resource, MOPED 2.5 now
      includes gene relative expression data in addition to protein absolute and
      relative expression data from over 250 large-scale experiments. To facilitate
      accurate integration of experiments and increase reproducibility, MOPED provides
      extensive metadata through the Data-Enabled Life Sciences Alliance (DELSA Global,
      http://delsaglobal.org ) metadata checklist. MOPED 2.5 has greatly increased the
      number of proteomics absolute and relative expression records to over 500,000, in
      addition to adding more than four million transcriptomics relative expression
      records. MOPED has an intuitive user interface with tabs for querying different
      types of omics expression data and new tools for data visualization. Summary
      information including expression data, pathway mappings, and direct connection
      between proteins and genes can be viewed on Protein and Gene Details pages. These
      connections in MOPED provide a context for multi-omics expression data
      exploration. Researchers are encouraged to submit omics data which will be
      consistently processed into expression summaries. MOPED as a multi-omics data
      resource is a pivotal public database, interdisciplinary knowledge resource, and
      platform for multi-omics understanding.

PMID- 24910946
TI  - Medium-term variability of the human serum metabolome in the Atherosclerosis Risk
      in Communities (ARIC) study.
AB  - Metabolomics is a systems biology tool providing small molecule signatures of
      disease etiology. In order to estimate the biologic variability of the human
      serum metabolome, this study calculated intraclass correlation coefficients
      (ICCs) for 178 stably-detected metabolites measured by untargeted
      chromatography/mass spectrometry. We studied a subsample of 60 participants (57%
      males, 70% Caucasians, aged 73.77+/-5.3 years) in the Atherosclerosis Risk in
      Communities (ARIC) Study who provided two fasting serum samples 4-6 weeks apart.
      The median ICC across all metabolites was 0.60, and 82% of metabolites had at
      least fair variability (i.e., ICC>= 0.40). There was variation in the medium-term
      variability among metabolites, with those in the pathways of amino acid and lipid
      metabolism showing relatively high ICCs, and those in the carbohydrate pathway
      showing relatively low ICCs. The results of this study provide a valuable
      resource for future study design and outcome interpretation of mass spectrometry
      based metabolomic studies in epidemiology.

PMID- 24910948
TI  - Relevance of neuronal and glial NPC1 for synaptic input to cerebellar Purkinje
      cells.
AB  - Niemann-Pick type C disease is a rare and ultimately fatal lysosomal storage
      disorder with variable neurologic symptoms. The disease-causing mutations concern
      NPC1 or NPC2, whose dysfunction entails accumulation of cholesterol in the
      endosomal-lysosomal system and the selective death of specific neurons, namely
      cerebellar Purkinje cells. Here, we investigated whether neurodegeneration is
      preceded by an imbalance of synaptic input to Purkinje cells and whether neuronal
      or glial absence of NPC1 has different impacts on synapses. To this end, we
      prepared primary cerebellar cultures from wildtype or NPC1-deficient mice that
      are glia-free and highly enriched with Purkinje cells. We report that lack of
      NPC1 in either neurons or glial cells did not affect the excitability of Purkinje
      cells, the formation of dendrites or their excitatory synaptic activity. However,
      simultaneous absence of NPC1 from neuronal and glial cells impaired the
      presynaptic input to Purkinje cells suggesting a cooperative effect of neuronal
      and glial NPC1 on synapses.

PMID- 24910947
TI  - CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor
      causes apoptotic destruction of human B-precursor leukemia cells.
AB  - We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal
      nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site
      inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific
      monoclonal antibody directed against radiation-resistant CD19-receptor positive
      aggressive B-precursor acute lymphoblastic leukemia (ALL) cells. The biotargeted
      C61-LNP were more potent than untargeted C61-LNP and consistently caused
      apoptosis in B-precursor ALL cells. The CD19-directed C61-LNP also destroyed B
      precursor ALL xenograft cells and their leukemia-initiating in vivo clonogenic
      fraction. This unique nanostructural therapeutic modality targeting the SYK
      dependent anti-apoptotic blast cell survival machinery shows promise for
      overcoming the clinical radiochemotherapy resistance of B-precursor ALL cells. 

PMID- 24910949
TI  - Engaging patients and clinicians in treating tobacco addiction.

PMID- 24910950
TI  - A robust DNA interface on a silicon electrode.
AB  - Two different interfaces prepared via UV-hydrosilylation of undecylenic acid and
      1,8-nonadiyne on silicon(111) have been explored to develop a robust
      electrochemical DNA sensor. Electrodes modified with undecylenic acid were found
      to stably immobilise DNA but could not resist the growth of insulating oxides,
      whereas 1,8-nonadiyne modified electrodes satisfy both requirements. 

PMID- 24910951
TI  - Effects of a 10-week in-season eccentric-overload training program on muscle
      injury prevention and performance in junior elite soccer players.
AB  - PURPOSE: To analyze the effect of an eccentric-overload training program (ie,
      half-squat and leg-curl exercises using flywheel ergometers) with individualized
      load on muscle-injury incidence and severity and performance in junior elite
      soccer players. METHODS: Thirty-six young players (U-17 to U-19) were recruited
      and assigned to an experimental (EXP) or control group (CON). The training
      program consisted of 1 or 2 sessions/wk (3-6 sets with 6 repetitions) during 10
      wk. The outcome measured included muscle injury (incidence per 1000 h of exposure
      and injury severity) and performance tests (countermovement jump [CMJ], 10-m and
      20-m sprint test). RESULTS: Between-groups results showed a likely (ES: 0.94)
      lower number of days of absence per injury and a possible decrement of incidence
      per 1000 h of match play in EXP than in CON. Regarding muscle performance, a
      substantial better improvement (likely to very likely) was found in 20-m sprint
      time (ES: 0.37), 10-m flying-sprint time (ES: 0.77), and CMJ (ES: 0.79) for EXP
      than for CON. Within-group analysis showed an unclear effect in each variable in
      CON. Conversely, substantial improvements were obtained in CMJ (ES: 0.58), 20-m
      sprint time (ES: 0.32), 10-m flying-sprint time (ES: 0.95), and injury severity
      (ES: 0.59) in EXP. Furthermore, a possible decrement in total injury incidence
      was also reported in EXP. CONCLUSIONS: The eccentric-based program led to a
      reduction in muscle-injury incidence and severity and showed improvements in
      common soccer tasks such as jumping ability and linear-sprinting speed.

PMID- 24910952
TI  - Preloaded time trial to assess load carriage performance.
AB  - The relevance and importance of load carriage in recreational and occupational
      tasks has stimulated a large body of research. Exercise protocols have been
      criticized for a lack of relevance to occupational activities; accordingly, the
      aim of this study was to assess the reliability of a preloaded time-trial
      protocol for load carriage assessment. After full familiarization, 8 healthy
      males performed 2 trials separated by 1 week. Each trial comprised 60-minute
      walking at 6.5 km.h and 0% gradient (LC), 15 minutes seated recovery followed by
      a 2.4-km time-trial (LCTT). All trials were performed wearing a 25-kg backpack.
      Performance time was 16.71 +/- 1.82 minutes and 16.37 +/- 1.78 minutes for LCTT 1
      and 2, respectively with a mean difference of -0.34 +/- 0.89 minutes. Using log
      ratio limits of agreement, the mean bias was 1.02 and random error component of
      the agreement ratio was 1.11. The intraclass correlation was 0.85, coefficient of
      variation was 10.5%, and Cohen's d was 0.35. The protocol demonstrated a very
      good level of reliability. We present a novel and reliable preloaded time-trial
      protocol that more closely reflects operational activities and can be used to
      quantify load carriage performance. This protocol provides greater ecologically
      validity regarding physical demands of load carriage activities than those
      adopted previously and provides an excellent tool for the strength and
      conditioning practitioner to assess individual load carriage performance.

PMID- 24910953
TI  - Precooling does not improve 2,000-m rowing performance of females in hot, humid
      conditions.
AB  - Precooling lowers skin (Tsk) and core temperature (Tre) and can improve
      performance in hot conditions, but has predominantly been studied in males. This
      study investigated the effects of precooling on self-paced 2,000-m rowing
      performance, within females, in hot, humid conditions. Eight physically active
      females (19.9 +/- 1.5 years, 66.8 +/- 3.1 kg, 30.0 +/- 5.0% body fat) performed
      2,000-m rows in a randomized order within 3 conditions {control (CONT) (20
      degrees  C, 40% relative humidity [RH]); hot (HOT) (35 degrees  C, 60% RH);
      precooling (PREC) (35 degrees  C, 60% RH, preceded by precooling)}. The
      precooling condition consisted of 20-minute precooling with a cold water shower,
      followed by a 2,000-m row. In contrast, CONT and HOT consisted of 20-minute
      passive rest in place of precooling. Tre, Tsk, and power output were recorded
      every 100 m of the rows. Muscle temperature (Tmu) was recorded at baseline, after
      20-minute passive rest/precooling and post-row. No differences were observed
      between conditions for performance time (CONT, 8.89 +/- 0.45 minutes; HOT, 9.01
      +/- 0.55 minutes; PREC, 8.87 +/- 0.48 minutes; p = 0.42). Mean Tre during the row
      was not different between conditions (CONT, 37.8 +/- 0.2 degrees  C; HOT, 37.7 +/
      0.3 degrees  C; PREC, 37.5 +/- 0.2 degrees  C; p = 0.12; main effect), although
      lower Tre was observed at 1,600 and 1,800 m in PREC compared with HOT (p <=
      0.05). Tmu was significantly reduced after precooling (p = 0.03). Precooling did
      not enhance 2,000-m rowing performance, despite differences in Tre, Tsk, and Tmu.
      The lack of observed improvement in rowing performance after cold shower
      precooling may have been due to the short exercise time. An improvement in
      performance may have been observed using an alternate method of precooling, which
      has been shown to be ergogenic in other sports.

PMID- 24910954
TI  - Effects of tapering with light vs. heavy loads on track and field throwing
      performance.
AB  - The purpose of the study was to investigate the effects of power training with
      light vs. heavy loads during the tapering phases of a double periodized training
      year on track and field throwing performance. Thirteen track and field throwers
      aged 16-26 years followed 8 months of systematic training for performance
      enhancement aiming at 2 tapering phases during the winter and the spring
      competition periods. Athletes performed tapering with 2 different resistance
      training loads (counterbalanced design): 7 athletes used 30% of 1 repetition
      maximum (1RM) light-load tapering (LT), and 6 athletes used the 85% of 1RM heavy
      load tapering (HT), during the winter tapering. The opposite was performed at the
      spring tapering. Before and after each tapering, throwing performance, 1RM
      strength, vertical jumping, rate of force development (RFD), vastus lateralis
      architecture, and rate of perceived exertion were evaluated. Throwing performance
      increased significantly by 4.8 +/- 1.0% and 5.6 +/- 0.9% after LT and HT,
      respectively. Leg press 1RM and squat jump power increased more after HT than LT
      (5.9 +/- 3.2% vs. -3.4 +/- 2.5%, and 5.1 +/- 2.4% vs. 0.9 +/- 1.4%, respectively,
      p <= 0.05). Leg press RFD increased more in HT (38.1 +/- 16.5%) compared with LT
      (-2.9 +/- 6.7%), but LT induced less fatigue than HT (4.0 +/- 1.5 vs. 6.7 +/-
      0.9, p <= 0.05). Muscle architecture was not altered after either program. These
      results suggest that performance increases similarly after tapering with LT or HT
      in track and field throwers, but HT leads to greater increases in strength, whole
      body power, and RFD.

PMID- 24910955
TI  - Repeated sprint ability in young soccer players at different game stages.
AB  - The purpose of this study was to determine the repeated sprint ability (RSA) of
      young (16.9 +/- 0.5 years) soccer players at different game stages. Players
      performed repeated sprint test (RST) (12 * 20 m) after warm-up before a game, at
      half-time, and after a full soccer game, each on a different day, in a random
      order. The ideal (fastest) sprint time (IS) and total (accumulative) sprint time
      (TS) were significantly slower at the end of the game compared with those after
      the warm-up before the game (p < 0.01 for each). Differences between IS and TS
      after the warm-up before the game and at half-time, and between half-time and end
      of the game, were not statistically significant. There was no significant
      difference in the performance decrement during the RST after warm-up before the
      game, at half-time, or the end of the game. Significant negative correlation was
      found between predicted V[Combining Dot Above]O2 and the difference between TS
      after the warm-up before the game and the end of the game (r = -0.52), but not
      between predicted V[Combining Dot Above]O2 and the difference in any of the RST
      performance indices between warm-up before the game and half-time, or between
      half-time and the end of the game. The findings indicate a significant RSA
      reduction only at the end but not at the half-time of a soccer game. The results
      also suggest that the contribution of the aerobic system to soccer intensity
      maintenance is crucial, mainly during the final stages of the game.

PMID- 24910956
TI  - Power, fatigue, and recovery changes in national collegiate athletic association
      division I hockey players across a competitive season.
AB  - This study aimed to evaluate changes in pre- to postseason power output, fatigue,
      and recovery during a repeated sprint test. Twenty National Collegiate Athletic
      Association Division I men's hockey athletes performed identical sessions of
      repeated sprint work pre- and postseason. The repeated sprint test consisted of 5
      sets of 45 seconds of repeated sprint work with 90 seconds of rest in between
      each series of sprints. Power output (W), decrement, and recovery scores (RECs)
      were determined using raw data from a nonmotorized treadmill. Ratings of
      perceived exertion were recorded after, and perceived readiness (PR) recorded
      before, each series of sprints. Mean power was significantly higher in preseason
      vs. postseason performance during sprint 1 (760.6 vs. 691.3 W; p = 0.03), sprint
      2 (719.9 vs 657.0 W; p = 0.05), sprint 4 (648.4 vs 588.9 W; p = 0.04), and sprint
      5 (656.6 vs. 586.8 W, p = 0.04). Ratings of perceived exertion were significantly
      higher during sprints 3, 4, and 5 postseason with PR significantly higher
      (indicating less readiness) before sprints 3 and 4. There were no significant
      differences in REC or decrement score. Overall, athletes were unable to maintain
      power during subsequent repeated sprint work during postseason. The degree to
      which the athletes fatigued and recovered between sprints did not change between
      pre- and postseason testing, however, athletes exhibit increased perceptual
      strain during the repeated sprint work. These data indicate meaningful
      performance and perceptual differences throughout the competitive season in
      collegiate-level hockey players.

PMID- 24910957
TI  - Establishing normative data for the special judo fitness test in female athletes
      using systematic review and meta-analysis.
AB  - Conflicting results have been documented in the Special Judo Fitness Test (SJFT)
      for mean parameters of performance between male and female judo athletes matched
      by age and competitive level. Therefore, it is debatable whether previously
      established norms for the SJFT prepared for men, should be adopted for use in
      women. The goal of this investigation was to prepare standards to allow coaches
      and researchers to control and evaluate training effects in female judoka.
      Systematic review was used to compile previously published scientific studies
      containing information on female judo athletes who were tested using the SJFT.
      The results were derived using meta-analysis and included data obtained from 11
      relevant studies published between January 1997 and December 2013. Combined mean
      and SDs were computed based on studies containing 161 individual results from the
      SJFT. A 5 degrees  scale was adopted as follows: Excellent = highest 5%, Good =
      next highest 15%, Regular = middle 60%, Poor = next lowest 15%, and Very poor =
      lowest 5%. The results of the current investigation provide normative data for
      the SJFT for junior and senior female judoka. Classification for each of the
      parameters of the SJFT, including number of throws completed during the test,
      heart rate (HR) measured immediately after the effort, HR after a 1-minute
      recovery period and SJFT index, were established. This normative data can be used
      in the design of training programs for female judoka, as well as evaluation after
      training, and in preparation for competition.

PMID- 24910958
TI  - Relationship Between Selected Strength and Power Assessments to Peak and Average
      Velocity of the Drive Block in Offensive Line Play.
AB  - Jacobson, BH, Conchola, EC, Smith, DB, Akehi, K, and Glass, RG. Relationship
      between selected strength and power assessments to peak and average velocity of
      the drive block in offensive line play. J Strength Cond Res 30(8): 2202-2205,
      2016-Typical strength training for football includes the squat and power clean
      (PC) and routinely measured variables include 1 repetition maximum (1RM) squat
      and 1RM PC along with the vertical jump (VJ) for power. However, little research
      exists regarding the association between the strength exercises and velocity of
      an actual on-the-field performance. The purpose of this study was to investigate
      the relationship of peak velocity (PV) and average velocity (AV) of the offensive
      line drive block to 1RM squat, 1RM PC, the VJ, body mass (BM), and body
      composition. One repetition maximum assessments for the squat and PC were
      recorded along with VJ height, BM, and percent body fat. These data were
      correlated with PV and AV while performing the drive block. Peal velocity and AV
      were assessed using a Tendo Power and Speed Analyzer as the linemen fired, from a
      3-point stance into a stationary blocking dummy. Pearson product analysis yielded
      significant (p <= 0.05) correlations between PV and AV and the VJ, the squat, and
      the PC. A significant inverse association was found for both PV and AV and body
      fat. These data help to confirm that the typical exercises recommended for
      American football linemen is positively associated with both PV and AV needed for
      the drive block effectiveness. It is recommended that these exercises remain the
      focus of a weight room protocol and that ancillary exercises be built around
      these exercises. Additionally, efforts to reduce body fat are recommended. 

PMID- 24910959
TI  - Synthesis of SnTe nanoplates with {100} and {111} surfaces.
AB  - SnTe is a topological crystalline insulator that possesses spin-polarized, Dirac
      dispersive surface states protected by crystal symmetry. Multiple surface states
      exist on the {100}, {110}, and {111} surfaces of SnTe, with the band structure of
      surface states depending on the mirror symmetry of a particular surface. Thus, to
      access surface states selectively, it is critical to control the morphology of
      SnTe such that only desired crystallographic surfaces are present. Here, we grow
      SnTe nanostructures using vapor-liquid-solid and vapor-solid growth mechanisms.
      Previously, SnTe nanowires and nanocrystals have been grown [Saghir et al. Cryst.
      Growth Des. 2014, 14, 2009-2013; Safdar et al. Cryst. Growth Des. 2014, 14, 2502
      2509; Safdar et al. Nano Lett. 2013, 13, 5344-5349; Li et al. Nano Lett. 2013,
      13, 5443-5448]. In this report, we demonstrate the synthesis of SnTe nanoplates
      with lateral dimensions spanning tens of micrometers and thicknesses of a few
      hundred nanometers. The top and bottom surfaces are either (100) or (111),
      maximizing topological surface states on these surfaces. Magnetotransport on
      these SnTe nanoplates shows a high bulk carrier density, consistent with bulk
      SnTe crystals arising due to defects such as Sn vacancies. In addition, we
      observe a structural phase transition in these nanoplates from the high
      temperature rock salt to a low-temperature rhombohedral structure. For nanoplates
      with a very high carrier density, we observe a slight upturn in resistance at low
      temperatures, indicating electron-electron interactions.

PMID- 24910960
TI  - Emergency ultrasound of acute scrotal pain.
AB  - Patients presenting with acute scrotal pain to the emergency department require a
      timely diagnosis. Although the differential diagnosis can be extensive and varies
      with age, there are a few conditions that are considered true surgical
      emergencies. These include torsion of the spermatic cord, incarcerated hernia
      with strangulation, testicular trauma leading to rupture or organ-threatening
      hematomas, and Fournier's gangrene. These are conditions that need to be kept in
      mind by the physician when approaching such patients. Other causes such as
      epididymitis or orchitis need to be distinguished, and although not requiring
      emergency surgery, still require urgent diagnosis and treatment. Diagnostic
      ultrasound can accurately diagnose many acute conditions of the scrotum, and
      emergency physicians have come to utilize it to advance their diagnostic acumen.
      This educational review article discusses the current literature and the use of
      emergency ultrasound in patients presenting with scrotal pain as well as scanning
      approaches and common sonographic findings. 

PMID- 24910961
TI  - Decreased general condition in the emergency department: high in-hospital
      mortality and a broad range of discharge diagnoses.
AB  - BACKGROUND: Decreased general condition (DGC) is a frequent presenting complaint
      within the Adaptive Triage Process. DGC describes a nonspecific decline in health
      and well-being, and it is common among elderly patients in the emergency
      department (ED). AIM: The aim of this study was to compare the in-hospital
      mortality among patients presenting with DGC with that among patients in the
      corresponding triage category presenting with other complaints to an ED. The
      secondary aim was to describe the discharge diagnoses of patients presenting with
      DGC. METHODS: All patients admitted to Sodersjukhuset from the ED in 2008 were
      included. The difference in the in-hospital mortality rate was stratified for
      triage category at the ED, between patients with DGC (n=1182) and those with all
      other presenting complaints (n=20 775), and assessed with sex-adjusted and age
      adjusted logistic regression models. Discharge diagnoses were assessed as the
      primary discharge diagnosis according to International Statistical Classification
      of Diseases and Related Health Problems 10th revision (ICD-10) in the medical
      discharge notes. RESULTS: A total of 1182 patients with DGC at the ED were
      admitted for in-hospital care, and they had a four-fold risk of suffering an in
      hospital death [odds ratio 4.74 (95% confidence interval 3.88-5.78)] compared
      with patients presenting with other presenting complaints. The most common
      discharge diagnoses were diseases of the circulatory system (14%), respiratory
      system (14%), and genitourinary system (10%). INTERPRETATION: Patients presenting
      with DGC to an ED often receive low triage priority, frequently require admission
      for in-hospital care, and, because of the three-fold increased risk of in
      hospital death compared with others, belong to a high-risk group.

PMID- 24910962
TI  - Can today's house officers teach effectively? An assessment in undergraduate
      emergency training.
AB  - BACKGROUND: Previous publications describe house officers (HOs) as unaware of
      their ineffective teaching skills. OBJECTIVE: The aim of this study was to
      evaluate the role of teaching seniority in the comparison of teaching skills
      between HOs and faculty. MATERIALS AND METHODS: Ten HOs (F: n=4, M: n=6, age:
      35.1+/-6.8 years) and nine faculty (F: n=3, M: n=6, age: 41.4+/-4.9 years) who
      actively teach undergraduate emergency medicine were immediately evaluated at the
      end of the course by their students using the questionnaire SFDP26. The
      questionnaire consists of one item on 'overall teaching effectiveness' (OTE)
      (1=very poor to 5=excellent) and 25 items measured on a five-point Likert scale
      (1-5=strongly disagree to strongly agree) divided into seven subscales: 1,
      'establishing the learning climate' (LC); 2, 'control of session' (CS); 3,
      'communication of goals' (CG); 4, 'facilitating understanding and retention'
      (UR); 5, 'evaluation' (E); 6, 'feedback' (FB) and 7, 'promoting self-directed
      learning' (SL). The sample included 173 medical students in their third year of
      training who were randomly assigned to the instructors. A Mann-Whitney U-test was
      used to calculate group-related differences (resident vs. teaching faculty). For
      significant differences, effect size was calculated (r=Z/?N). RESULTS: No sex
      related differences were found. Significantly better ratings for HOs were found
      in subscales: 1, 'LC' (P=0.001; r=0.20); 2, 'CS' (P=0.037; r=0.15); 5, 'E'
      (P=0.007; r=0.20); 6, 'FB' (P=0.001; r=0.23); 7, 'SL' (P=0.004; r=0.24) and 'OTE'
      (P=0.027; r=0.26). CONCLUSION: From a learner's perspective, the quality of
      teaching provided by HOs was rated at least similar and mostly better overall
      than that provided by faculty. These findings contradict results from previous
      studies on the quality of HO teaching and therefore warrant further assessment.

PMID- 24910963
TI  - Can emergency medicine practitioners predict disposition of psychiatric patients
      based on a brief medical evaluation?
AB  - OBJECTIVE: Emergency medicine practitioners (EMPs) often provide 'medical
      clearance' before evaluation by a psychiatry practitioner (PP). We set out to
      determine the level of agreement between EMP impression and disposition as
      determined by PPs. PATIENTS AND METHODS: This was a prospective observational
      study in an urban tertiary teaching hospital emergency department. We collected
      data from February to April 2011. We used a convenience sample of patient
      encounters evaluated by EMPs and subsequent referral for psychiatric evaluation.
      We asked EMPs whether they thought the patients would be admitted or discharged
      following psychiatric evaluation, and if discharged, whether to outpatient
      psychiatric follow-up or to no follow-up. EMPs were asked to base their opinion
      upon their general impression following their brief medical evaluation. They were
      not given guidelines on which to base their decision. The EMPs were blind to PP
      decisions. The kappa-statistic was used to calculate agreement between the EMP's
      impression and disposition decision by the PP. We excluded patients who were
      acutely intoxicated, in police custody, or lived in an extended care facility.
      RESULTS: We included 156 patient encounters over the study period and had
      complete data for 152 encounters. Of these, 86 (55%) were admitted, 46 (30%) were
      discharged with no specific psychiatric follow-up, and 20 (13%) were discharged
      with a follow-up plan. EMPs predicted the exact disposition in 77/152 (51%) cases
      (kappa=0.264, 95% confidence interval 0.77-0.333). Agreement was higher for
      admitted patients, with EMPs predicting inpatient admission for 57/86 (66%) of
      these patients. Other factors associated with higher agreement scores were years
      in emergency medicine practice by the EMP and suicidal ideation by the patient.
      CONCLUSION: EMPs did not reliably predict psychiatric disposition decisions based
      on clinical 'gestalt'. Future research will focus on clinical guidelines to help
      EMPs better independently assess need for emergency psychiatric services.

PMID- 24910964
TI  - Rapid infusion pump overestimates delivered flow during rapid vascular filling: a
      bench study.
AB  - OBJECTIVE: Despite now being rarely used in the prehospital and emergency
      department arena because of their excessive length and low inner diameter, narrow
      bore central venous catheters (CVC) are sometime used to perform fluid
      resuscitation using a rapid infusion pump to enhance delivered flow. In this
      bench study, we tested the hypothesis that the delivered flow rate downstream
      from the catheter connected to a rapid infusion pump would be significantly lower
      than the preset flow rate, and this difference would be affected by the catheter
      size. MATERIALS AND METHODS: Eight units of each type of catheter [two 15 and 20
      cm narrow-bore CVC and three 14, 16 and 18 G peripheral venous catheters (PVC)]
      were connected to a rapid infusion device and were tested with physiological
      saline. Measurements were repeated using glycerol solution with a viscosity
      similar to that of packed red blood cells. Infusion pump flow rates were preset
      to 100, 200, 300 and 400 ml/min. Flow rates were measured downstream from
      catheters, each connected to a rapid infusion device. RESULTS: The downstream
      flow rate remained lower than the preset flow rate except with the 14 and the 16
      G PVC at 100 ml/min (P<0.001). The type of catheter significantly impacted the
      flow rates measured with physiological saline (F4,105=1008.83, P<0.001) and
      glycerol solution (F4,105=1843.46, P<0.001). CONCLUSION: Using a rapid infusion
      device, the delivered flow rate was lower than the preset flow rate. Even PVCs
      are better than narrow-bore CVC, neither is the most suitable cannula for
      patients requiring massive resuscitation.

PMID- 24910965
TI  - Goal-directed ultrasound in emergency medicine: evaluation of a specific training
      program using an ultrasonic stethoscope.
AB  - OBJECTIVE: This observational study aimed to define the learning curve in goal
      directed ultrasound (US) after a 2-day training course dedicated to novice
      emergency residents. MATERIALS AND METHODS: After completion of the training
      program, 180 patients requiring goal-directed US examination were examined by a
      resident and by an experienced investigator. The main endpoints were the
      diagnostic agreement between the two operators for 14 clinical questions, the
      duration of the examinations, the number of nonaddressed questions, and the final
      diagnosis. All criteria were analyzed according to the experience of the resident
      every 10 examinations. RESULTS: After 30 supervised examinations, residents
      adequately assessed with a very good or considerable agreement global left
      ventricular systolic dysfunction [kappa=0.92; 95% confidence interval (CI): 0.80
      1], severe right ventricular dilation (kappa=0.73; 95% CI: 0.37-1), inferior vena
      cava diameter (kappa=0.88; 95% CI: 0.71-1), and pericardial effusion (kappa=0.85;
      95% CI: 0.55-1). In general US, 20 supervised examinations were required to
      diagnose intraperitoneal effusion (kappa=0.81; 95% CI: 0.61-1), cholelithiasis
      (kappa=0.73; 95% CI: 0.36-1), obstructive uropathy (kappa=0.85; 95% CI: 0.56-1),
      bladder distention (kappa=1; 95% CI: 1-1), abdominal aortic aneurism (kappa=0.9;
      95% CI: 0.74-1), alveolar interstitial pattern (kappa=0.87; 95% CI: 0.74-0.99),
      consolidated lung (kappa=0.83; 95% CI: 0.68-0.97), or pleural effusion
      (kappa=0.89; 95% CI: 0.77-1). After 30 supervised examinations, the overall
      diagnostic accuracy was judged excellent between the two investigators, with a
      significant improvement during the learning curve. CONCLUSION: The performance of
      30 supervised and goal-oriented examinations appeared adapted to adequately
      answer clinical questions covered by core applications of emergency US.

PMID- 24910966
TI  - The Medicare data release conundrum.

PMID- 24910967
TI  - Iron(III)-salan complexes catalysed highly enantioselective fluorination and
      hydroxylation of beta-keto esters and N-Boc oxindoles.
AB  - Chiral iron(iii)-salan complexes catalysed highly enantioselective alpha
      fluorination and alpha-hydroxylation of beta-keto esters and N-Boc oxindoles to
      give the corresponding products in high yields and good-to-excellent ee values
      under mild reaction conditions. 

PMID- 24910968
TI  - Microvascular imaging: techniques and opportunities for clinical physiological
      measurements.
AB  - The microvasculature presents a particular challenge in physiological measurement
      because the vessel structure is spatially inhomogeneous and perfusion can exhibit
      high variability over time. This review describes, with a clinical focus, the
      wide variety of methods now available for imaging of the microvasculature and
      their key applications. Laser Doppler perfusion imaging and laser speckle
      contrast imaging are established, commercially-available techniques for
      determining microvascular perfusion, with proven clinical utility for
      applications such as burn-depth assessment. Nailfold capillaroscopy is also
      commercially available, with significant published literature that supports its
      use for detecting microangiopathy secondary to specific connective tissue
      diseases in patients with Raynaud's phenomenon. Infrared thermography measures
      skin temperature and not perfusion directly, and it has only gained acceptance
      for some surgical and peripheral microvascular applications. Other emerging
      technologies including imaging photoplethysmography, optical coherence
      tomography, photoacoustic tomography, hyperspectral imaging, and tissue viability
      imaging are also described to show their potential as techniques that could
      become established tools for clinical microvascular assessment. Growing interest
      in the microcirculation has helped drive the rapid development in perfusion
      imaging of the microvessels, bringing exciting opportunities in microvascular
      research. 

PMID- 24910969
TI  - Metabolic and safety issues for multiple sclerosis pharmacotherapy--opportunities
      for personalised medicine.
AB  - INTRODUCTION: A number of disease-modifying therapies have become available to
      treat multiple sclerosis (MS) in recent years. As the effects of these
      medications are unpredictable and they are generally used for a number of years,
      the selection of the most appropriate disease-modifying agent must be based on
      the long-term efficacy and toxicity profile, thus strategies to personalise
      treatment to optimise responses may be potentially very useful. AREAS COVERED:
      This review provides an overview of the efficacy and toxicity of disease
      modifying agents used in MS and specifically discusses any metabolic side effects
      and advances in personalising the use of each of these agents. Medline and EMBASE
      were searched for any articles regarding the efficacy, toxicity and personalised
      use of the medicines discussed in this review. EXPERT OPINION: Disease-modifying
      agents used to treat MS differ substantially in their efficacy and toxicity
      profile, but metabolic side effects appear to be limited to alemtuzumab,
      teriflunomide and IFN-beta. Although personalised treatment strategies to assist
      in selection of the most appropriate disease-modifying agent for MS are limited,
      there is substantial potential to use genetic sub-studies of the many recent
      trials investigating disease-modifying agents to develop personalised treatment
      strategies.

PMID- 24910970
TI  - Production of the sesquiterpene (+)-valencene by metabolically engineered
      Corynebacterium glutamicum.
AB  - The sesquiterpene (+)-valencene is an aroma compound of citrus fruits and is used
      to flavor foods and drinks. Biosynthesis of (+)-valencene starts from farnesyl
      pyrophosphate, an intermediate of carotenoid biosynthesis. Corynebacterium
      glutamicum, the workhorse of the million-ton scale amino acid industry, is
      naturally pigmented as it synthesizes the rare fifty carbon atoms (C50)
      containing carotenoid decaprenoxanthin. Since the carotenoid pathway of this Gram
      positive bacterium has previously been engineered for efficient production of
      several C50 and C40 carotenoids, its potential to produce a sesquiterpene was
      assessed. Growth of C. glutamicum was negatively affected by (+)-valencene, but
      overlaying n-dodecane as organic phase for extraction of (+)-valencene was shown
      to be biocompatible. Heterologous expression of the (+)-valencene synthase gene
      from the sweet orange Citrus sinensis was not sufficient to enable (+)-valencene
      production, likely because provision of farnesyl pyrophosphate (FPP) by
      endogenous prenyltransferases was too low. However, upon deletion of two
      endogenous prenyltransferase genes and heterologous expression of either FPP
      synthase gene ispA from Escherichia coli or ERG20 from Saccharomyces cerevisiae
      (+)-valence production by C. sinensis valencene synthase was observed. Employing
      the valencene synthase from Nootka cypress improved (+)-valencene titers 10 fold
      to 2.41+/-0.26mgl(-1) (+)-valencene, which is equivalent to 0.25+/-0.03mgg(-1)
      cell dry weight (CDW). This is the first report on sesquiterpene overproduction
      by recombinant C. glutamicum. 

PMID- 24910971
TI  - Expanding the laccase-toolbox: a laccase from Corynebacterium glutamicum with
      phenol coupling and cuprous oxidase activity.
AB  - Laccases are oxidases with potential for application in biotechnology. Up to now
      only fungal laccases have been applied in technical processes, although bacterial
      laccases are generally easier to handle and more stable at alkaline pH values and
      elevated temperatures. To increase the toolbox of bacterial laccases and to
      broaden our knowledge about them, new enzymes have to be characterized. Within
      this study, we describe the new bacterial laccase CgL1 from Corynebacterium
      glutamicum. CgL1 was found to oxidize typical laccase substrates like 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulphonic acid), syringaldazine and 2,6
      dimethoxyphenol. The enzyme also demonstrates cuprous oxidase activity.
      Furthermore, CgL1 is active for several hours at temperatures up to 60 degrees C
      and at alkaline pH, as well as stable in different organic solvents. This makes
      CgL1 a potential candidate for technical applications. In addition, CgL1 was
      found to catalyze the CC/CO coupling of several phenolic compounds which can
      serve as precursors for the synthesis of natural products like antibiotics and
      phytohormones. This activity and product distribution were influenced by pH value
      and mediators used. 

PMID- 24910972
TI  - Transcriptome sequencing revealed the transcriptional organization at ribosome
      mediated attenuation sites in Corynebacterium glutamicum and identified a novel
      attenuator involved in aromatic amino acid biosynthesis.
AB  - The Gram-positive bacterium Corynebacterium glutamicum belongs to the order
      Corynebacteriales and is used as a producer of amino acids at industrial scales.
      Due to its economic importance, gene expression and particularly the regulation
      of amino acid biosynthesis has been investigated extensively. Applying the high
      resolution technique of transcriptome sequencing (RNA-seq), recently a vast
      amount of data has been generated that was used to comprehensively analyze the C.
      glutamicum transcriptome. By analyzing RNA-seq data from a small RNA cDNA library
      of C. glutamicum, short transcripts in the known transcriptional attenuators
      sites of the trp operon, the ilvBNC operon and the leuA gene were verified.
      Furthermore, whole transcriptome RNA-seq data were used to elucidate the
      transcriptional organization of these three amino acid biosynthesis operons. In
      addition, we discovered and analyzed the novel attenuator aroR, located upstream
      of the aroF gene (cg1129). The DAHP synthase encoded by aroF catalyzes the first
      step in aromatic amino acid synthesis. The AroR leader peptide contains the amino
      acid sequence motif F-Y-F, indicating a regulatory effect by phenylalanine and
      tyrosine. Analysis by real-time RT-PCR suggests that the attenuator regulates the
      transcription of aroF in dependence of the cellular amount of tRNA loaded with
      phenylalanine when comparing a phenylalanine-auxotrophic C. glutamicum mutant fed
      with limiting and excess amounts of a phenylalanine-containing dipeptide.
      Additionally, the very interesting finding was made that all analyzed attenuators
      are leaderless transcripts. 

PMID- 24910973
TI  - High level expression of Glomerella cingulata cutinase in dense cultures of
      Pichia pastoris grown under fed-batch conditions.
AB  - A Pichia pastoris transformant carrying the cutinase cDNA of Glomerella cingulata
      was over-expressed in a 5L bioreactor (2.0L working volume) under fed-batch
      conditions. Bioreactor experiments rely on varying selected parameters in
      repeated rounds of optimisation: here these included duration of induction, pH
      and temperature. Highest cell densities (320gL(-1) wet cell weight) with a
      cutinase production of 3800mgL(-1) and an activity of 434UmL(-1) were achieved
      24h after induction with methanol in basal salt medium (at pH 5 and 28 degrees
      C). Characterisation of the cutinase showed that it was stable between pH 6 and
      pH 11, had an optimum pH of 8.0 and retained activity for 30min at 50 degrees C
      (optimum temperature 25 degrees C).The preferred substrates of G. cingulata
      cutinase were the medium- to long-chain rho-nitrophenyl esters of rho
      nitrophenylcaprylate (C8), rho-nitrophenyllaurate (C12) and rho
      nitrophenylmyristate (C14), with the highest catalytic efficiency, kcat/Km of
      7.7+/-0.7mM(-1)s(-1) for rho-nitrophenylcaprylate. Microscopic analyses showed
      that the G. cingulata cutinase was also capable of depolymerising the high
      molecular weight synthetic polyester, polyethylene terephthalate. 

PMID- 24910974
TI  - Design and synthesis of novel 1,2,3-triazole derivatives of coronopilin as anti
      cancer compounds.
AB  - A series of 1,2,3-triazole coronopilin congeners have been designed and
      synthesized by employing click chemistry approach starting from parthenin and
      evaluated for their cytotoxicity against a panel of six human cancer cell lines
      (PC-3, THP-1, HCT-15, HeLa, A-549 and MCF-7). While many compounds exhibited
      significant anticancer activity, compound 3a, was found to be the most promising
      analogue in this series with IC50 values of 3.1 MUM on PC-3 cell line. Flow
      cytometric studies showed that 1,2,3-triazole derivative-3a induce dose dependent
      apoptosis in the sub G1 phase. This lead molecule-3a was further studied for NF
      kappaB (p65) transcription factor inhibitory activity using Elisa and western
      blotting analysis which confirmed concentration dependent inhibitory activity
      against NF-kappaB, p65 with 80% inhibition in 24 h at 100 MUM.

PMID- 24910975
TI  - Association of adrenal function and disease severity in community-acquired
      pneumonia.
AB  - INTRODUCTION: Rapid and accurate risk stratification in patients with community
      acquired pneumonia (CAP) is an unmet clinical need. Cortisol to
      dehydroepiandrosterone (DHEA) ratio was put forward as a prognostic marker in
      sepsis. We herein validated the prognostic value of the adrenal hormones DHEA,
      DHEA-Sulfate (DHEAS), cortisol/DHEA-, cortisol/DHEAS- and DHEA/DHEAS-ratios in
      patients with CAP. METHODS: We assessed severity of illness using the pneumonia
      severity index (PSI) and measured adrenal hormone concentrations in 179 serum
      samples of prospectively recruited patients hospitalized with CAP. We calculated
      spearman rank correlation, logistic regression analysis and Kaplan Meier curves
      to study associations of adrenal hormones and outcomes. RESULTS: There was a
      significant correlation between PSI score and total cortisol (r = 0.24, p =
      0.001), DHEAS (r = -0.23, p = 0.002), cortisol/DHEA (r = 0.23, p = 0.003),
      cortisol/DHEAS (r = 0.32, p = <0.0001) and DHEA/DHEAS (r = 0.20, p = 0.009). In
      age and gender adjusted logistic regression analysis, cortisol (OR:2.8, 95% CI:
      1.48-5.28) and DHEA (OR: 2.62,95% CI: 1.28-5.34), but not DHEAS and the different
      ratios were associated with all-cause mortality. The discriminatory accuracy of
      cortisol and DHEA in ROC analysis (area under the curve) was 0.74 and 0.61. In
      Kaplan Meier analysis, patients in the highest deciles of cortisol and DHEA (p =
      0.005 and p = 0.015), and to a lesser extent of cortisol/DHEAS ratio (p = 0.081)
      had a higher risk of death. CONCLUSION: Cortisol, DHEAS and their ratios
      correlate with CAP severity, and cortisol and DHEA predict mortality. Adrenal
      function in severe pneumonia may be an important factor for CAP outcomes.

PMID- 24910977
TI  - Spectroscopic investigations on the effect of N-acetyl-L-cysteine-capped CdTe
      Quantum Dots on catalase.
AB  - Quantum dots (QDs) are recognized as some of the most promising semiconductor
      nanocrystals in biomedical applications. However, the potential toxicity of QDs
      has aroused wide public concern. Catalase (CAT) is a common enzyme in animal and
      plant tissues. For the potential application of QDs in vivo, it is important to
      investigate the interaction of QDs with CAT. In this work, the effect of N-Acetyl
      L-cysteine-Capped CdTe Quantum Dots with fluorescence emission peak at 612 nm
      (QDs-612) on CAT was investigated by fluorescence, synchronous fluorescence,
      fluorescence lifetime, ultraviolet-visible (UV-vis) absorption and circular
      dichroism (CD) techniques. Binding of QDs-612 to CAT caused static quenching of
      the fluorescence, the change of the secondary structure of CAT and the alteration
      of the microenvironment of tryptophan residues. The association constants K were
      determined to be K288K=7.98*10(5)Lmol(-1) and K298K=7.21*10(5)Lmol(-1). The
      interaction between QDs-612 and CAT was spontaneous with 1:1 stoichiometry
      approximately. The CAT activity was also inhibited for the bound QDs-612. This
      work provides direct evidence about enzyme toxicity of QDs-612 to CAT in vitro
      and establishes a new strategy to investigate the interaction between enzyme and
      QDs at a molecular level, which is helpful for clarifying the bioactivities of
      QDs in vivo.

PMID- 24910976
TI  - Topical rapamycin as a treatment for fibrofolliculomas in Birt-Hogg-Dube
      syndrome: a double-blind placebo-controlled randomized split-face trial.
AB  - BACKGROUND: Birt-Hogg-Dube syndrome (BHD) is a rare autosomal dominant disorder
      characterised by the occurrence of benign, mostly facial, skin tumours called
      fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased
      renal cancer risk. Current treatments for fibrofolliculomas have high rates of
      recurrence and carry a risk of complications. It would be desirable to have a
      treatment that could prevent fibrofolliculomas from growing. Animal models of BHD
      have previously shown deregulation of mammalian target of rapamycin (mTOR).
      Topical use of the mTOR inhibitor rapamycin is an effective treatment for the
      skin tumours (angiofibromas) in tuberous sclerosis complex, which is also
      characterised by mTOR deregulation. In this study we aimed to determine if
      topical rapamycin is also an effective treatment for fibrofolliculomas in BHD.
      METHODS: We performed a double blinded, randomised, facial left-right controlled
      trial of topical rapamycin 0.1% versus placebo in 19 BHD patients. Trial duration
      was 6 months. The primary outcome was cosmetic improvement as measured by doctors
      and patients. Changes in fibrofolliculoma number and size were also measured, as
      was occurrence of side effects. RESULTS: No change in cosmetic status of
      fibrofolliculomas was reported in the majority of cases for the rapamycin treated
      (79% by doctors, 53% by patients) as well as the placebo treated facial sides
      (both 74%). No significant differences between rapamycin and placebo treated
      facial halves were observed (p = 1.000 for doctors opinion, p = 0.344 for
      patients opinion). No significant difference in fibrofolliculoma number or change
      in size of the fibrofolliculomas was seen after 6 months. Side effects occurred
      more often after rapamycin treatment (68% of patients) than after placebo (58% of
      patients; p = 0.625). A burning sensation, erythema, itching and dryness were
      most frequently reported. CONCLUSIONS: This study provides no evidence that
      treatment of fibrofolliculomas with topical rapamycin in BHD results in cosmetic
      improvement. TRIAL REGISTRATION: ClinicalTrials.gov NCT00928798.

PMID- 24910978
TI  - Infrared spectrum analysis of the dissociated states of simple amino acids.
AB  - In this work, we present detailed analyses of the dissociation of dilute aqueous
      solutions of glycine and of lysine over the range 1<pH<12. Using appropriate
      spectrum subtraction methods, we obtained ATR-IR spectra of the solvated species
      as a function of pH. Discernible changes in the ionic species were identified in
      the absorption region between 1800 and 1100 cm(-1). By applying peak
      deconvolution techniques to the spectra, we correctly interpret the apparent peak
      shift from 1615 to 1600 cm(-1) as being due to the receding NH3+ asymmetric
      deformation alongside the appearing COO- asymmetric stretching. The effect of
      aqueous solution environment was also investigated in terms of 10 and 100 mmol/L
      NaCl. Salt solution spectra at each pH were also subtracted from each solution
      phase spectrum. Analysis of the deconvoluted peak areas due to CO and COO- at pH
      ranges<4.5 and those due to NH2 and NH3+ for pH>8 resulted in consistent pKa
      values for the amino acids.

PMID- 24910979
TI  - Theoretical (in B3LYP/6-3111++G** level), spectroscopic (FT-IR, FT-Raman) and
      thermogravimetric studies of gentisic acid and sodium, copper(II) and cadmium(II)
      gentisates.
AB  - The DFT calculations (B3LYP method with 6-311++G(d,p) mixed with LanL2DZ for
      transition metals basis sets) for different conformers of 2,5-dihydroxybenzoic
      acid (gentisic acid), sodium 2,5-dihydroxybenzoate (gentisate) and copper(II) and
      cadmium(II) gentisates were done. The proposed hydrated structures of transition
      metal complexes were based on the results of experimental findings. The
      theoretical geometrical parameters and atomic charge distribution were discussed.
      Moreover Na, Cu(II) and Cd(II) gentisates were synthesized and the composition of
      obtained compounds was revealed by means of elemental and thermogravimetric
      analyses. The FT-IR and FT-Raman spectra of gentisic acid and gentisates were
      registered and the effect of metals on the electronic charge distribution of
      ligand was discussed. 

PMID- 24910981
TI  - Thermodynamic perturbation theory for self-assembling mixtures of divalent single
      patch colloids.
AB  - In this work we extend Wertheim's thermodynamic perturbation theory (TPT) to
      binary mixtures (species A and species B) of patchy colloids were each species
      has a single patch which can bond a maximum of twice (divalent). Colloids are
      treated as hard spheres with a directional conical association site. We restrict
      the system such that only patches between unlike species share attractions;
      meaning there are AB attractions but no AA or BB attractions. The theory is
      derived in Wertheim's two density formalism for one site associating fluids.
      Since the patches are doubly bondable, associated chains, of all chain lengths,
      as well as 4-mer rings consisting of two species A and two species B colloids are
      accounted for. With the restriction of only AB attractions, triatomic rings of
      doubly bonded colloids, which dominate in the corresponding pure component case,
      cannot form. The theory is shown to be in good agreement with Monte Carlo
      simulation data for the structure and thermodynamics of these patchy colloid
      mixtures as a function of temperature, density, patch size and composition. It is
      shown that 4-mer rings dominate at low temperature, inhibiting the polymerization
      of the mixture into long chains. Mixtures of this type have been recently
      synthesized by researchers. This work provides the first theory capable of
      accurately modeling these mixtures. 

PMID- 24910980
TI  - Antihypertensive agents and risk of Parkinson's disease: a nationwide cohort
      study.
AB  - BACKGROUND AND PURPOSE: Hypertension has been associated with Parkinson's disease
      (PD), but data on antihypertensive drugs and PD are inconclusive. We aim to
      evaluate antihypertensive drugs for an association with PD in hypertensive
      patients. METHODS: Hypertensive patients who were free of PD, dementia and stroke
      were recruited from 2005-2006 using Taiwan National Health Insurance Database. We
      examined the association between the use of calcium channel blockers (CCBs),
      angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers
      (ARBs) and the incidence of PD using beta-blockers as the reference. Cox
      regression model with time-varying medication use was applied. RESULTS: Among
      65,001 hypertensive patients with a mean follow-up period of 4.6 years, use of
      dihydropyridine CCBs, but not non-dihydropyridine CCBs, was associated with a
      reduced risk of PD (adjusted hazard ratio [aHR]  = 0.71; 95% CI, 0.57-0.90).
      Additionally, use of central-acting CCBs, rather than peripheral-acting ones, was
      associated with a decreased risk of PD (aHR = .69 [55-0.87]. Further decreased
      association was observed for higher cumulative doses of felodipine (aHR = 0.54
      [0.36-0.80]) and amlodipine (aHR = 0.60 [0.45-0.79]). There was no association
      between the use of ACEIs (aHR = 0.80 [0.64-1.00]) or ARBs (aHR = 0.86 [0.69
      1.08]) with PD. A potentially decreased association was only found for higher
      cumulative use of ACEIs (HR = 0.52 [0.34-0.80]) and ARBs (HR = 0.52 [0.33-0.80]).
      CONCLUSIONS: Our study suggests centrally-acting dihydropyridine CCB use and high
      cumulative doses of ACEIs and ARBs may associate with a decreased incidence of PD
      in hypertensive patients. Further long-term follow-up studies are needed to
      confirm the potential beneficial effects of antihypertensive agents in PD.

PMID- 24910982
TI  - Nanomolar levels of PAHs in extracts from urban air induce MAPK signaling in
      HepG2 cells.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that
      occur naturally in complex mixtures. Many of the adverse health effects of PAHs
      including cancer are linked to the activation of intracellular stress response
      signaling. This study has investigated intracellular MAPK signaling in response
      to PAHs in extracts from urban air collected in Stockholm, Sweden and Limeira,
      Brazil, in comparison to BP in HepG2 cells. Nanomolar concentrations of PAHs in
      the extracts induced activation of MEK4 signaling with down-stream increased gene
      expression of several important stress response mediators. Involvement of the
      MEK4/JNK pathway was confirmed using siRNA and an inhibitor of JNK signaling
      resulting in significantly reduced MAPK signaling transactivated by the AP-1
      transcription factors ATF2 and c-Jun. ATF2 was also identified as a sensitive
      stress responsive protein with activation observed at extract concentrations
      equivalent to 0.1 nM BP. We show that exposure to low levels of environmental PAH
      mixtures more strongly activates these signaling pathways compared to BP alone
      suggesting effects due to interactions. Taken together, this is the first study
      showing the involvement of MEK4/JNK/AP-1 pathway in regulating the intracellular
      stress response after exposure to nanomolar levels of PAHs in environmental
      mixtures.

PMID- 24910983
TI  - Highly expressed protein kinase A inhibitor alpha and suppression of protein
      kinase A may potentiate acetaminophen-induced hepatotoxicity.
AB  - Drug-induced hepatotoxicity is a serious adverse effect with high morbidity and
      mortality rates but substantial individual to individual variation is observed in
      its severity. Here we sought to discover factors determining the susceptibility
      to acetaminophen (APAP)-induced hepatotoxicity by comparing the global gene
      expression profile (27,342 genes) in pre-dose blood before APAP administration
      between susceptible and resistant animals (N=5) grouped based on the severity of
      hepatotoxicity. Forty-one genes were expressed differently (>1.5 fold change and
      p<0.05) between susceptible and resistant groups. Among them, protein kinase
      (cAMP-dependent) inhibitor alpha, Pkia, a member of protein kinase A (PKA)
      inhibitor family, was found to be most significantly and highly expressed in
      susceptible animals (~3.5 fold with p<0.01). To investigate the effects of PKA
      inhibition on APAP-induced hepatotoxicity, we pre-treated H-89, a potent and
      selective inhibitor of PKA, prior to APAP administration in vivo. As a result, H
      89 pretreatment significantly potentiated APAP-induced hepatotoxicity as
      determined by the increased serum alanine transaminase. These results were
      further corroborated by the exacerbation of APAP-induced glutathione depletion,
      suppression of antioxidant enzyme system, superoxide dismutase 1 and glutathione
      peroxidase 1, and peroxynitrite generation in the liver following H-89
      pretreatment, reflecting that PKA may be involved in the protection against, or
      attenuation of APAP-induced hepatotoxicity, and Pkia can be employed to screen
      individuals susceptible to APAP-induced hepatotoxicity.

PMID- 24910984
TI  - Corticosteroids found ineffective for phosgene-induced acute lung injury in rats.
AB  - Various therapeutic regimes have been proposed with limited success for treatment
      of phosgene-induced acute lung injury (P-ALI). Corticoids were shown to be
      efficacious against chlorine-induced lung injury but there is still controversy
      whether this applies also to P-ALI. This study investigates whether different
      regimen of curatively administered budesonide (BUD, 10 mg/kg bw, i.p. bid; 100
      mg/m(3)*30 min, nose-only inhalation), mometasone (MOM, 3 mg/kg bw, i.p. bid) and
      dexamethasone (DEX, 10, 30 mg/kg bw, i.p. bid), show efficacy to alleviate P-ALI.
      Efficacy of drugs was judged by nitric oxide (eNO) and carbon dioxide (eCO2) in
      exhaled air and whether these non-invasive biomarkers are suitable to assess the
      degree of airway injury (chlorine) relative to alveolar injury (phosgene). P-ALI
      related analyses included lung function (enhanced pause, Penh), morbidity,
      increased lung weights, and protein in bronchial alveolar lavage fluid (BALF) one
      day postexposure. One of the pathophysiological hallmarks of P-ALI was indicated
      by increased Penh lasting for approximately 20 h postexposure. Following the
      administration of BUD, this increase could be suppressed; however, without
      significant improvement in survival and lung edema (increased lung weights and
      BALF-protein). Collectively, protocols shown to be efficacious for chlorine (Chen
      et al., 2013) were ineffective and even increased adversity in the P-ALI model.
      This outcome warrants further study to seek for early biomarkers suitable to
      differentiate chlorine- and phosgene-induced acute lung injury at yet
      asymptomatic stage. The patterns of eNO and eCO2 observed following exposure to
      chlorine and phosgene may be suitable to guide the specialized clinical
      interventions required for each type of ALI.

PMID- 24910986
TI  - Understanding the risks associated with the use of new psychoactive substances
      (NPS): high variability of active ingredients concentration, mislabelled
      preparations, multiple psychoactive substances in single products.
AB  - New psychoactive substances (NPS), are now a large group of substances of abuse
      not yet completely controlled by international drug conventions, which may pose a
      public health threat. Anxiety, paranoia, hallucinations, seizures, hyperthermia
      and cardiotoxicity are some of the common adverse effects associated with these
      compounds. In this paper, three case reports taken from the archive of processed
      cases of the authors' laboratory are presented and discussed to stress the risks
      of possible adverse consequences for NPS users: in particular, (i) the risk
      deriving from the difficulty of predicting the actual consumed dose, due to
      variability of active ingredients concentration in consumed products, (ii) the
      risk deriving from the difficulty of predicting the actual active ingredients
      present in consumed products, as opposed to those claimed by the manufacturer,
      and (iii) the risk deriving from the difficulty of predicting the actual
      pharmacological and toxicological effects related to the simultaneous consumption
      of different psychoactive ingredients contained in single products, whose
      interactions are mostly unknown. Each of them individually provide a source of
      concern for possible serious health related consequences. However, they should be
      considered in conjunction with each others, with the worldwide availability of
      NPS through the web and also with the incessantly growing business derived from
      the manipulation and synthesis of new substances. The resulting scenario is that
      of a cultural challenge which demands a global approach from different fields of
      knowledge. 

PMID- 24910987
TI  - Use of a human skin in vitro model to investigate the influence of 'every-day'
      clothing and skin surface decontamination on the percutaneous penetration of
      organophosphates.
AB  - Organophosphates (OPs) are widely used in agriculture. Many studies have
      investigated the capability of personal protective equipment (PPE) to reduce
      chemical exposure; however, investigations into the protective effect of 'every
      day' clothing are rare. The purpose of this study was to investigate the
      protective effect of 'every-day' clothing against dermal exposure and to measure
      early decontamination of skin following exposure to chlorpyrifos and dichlorvos.
      Using human skin in vitro, absorption of (14)C-labelled chlorpyrifos (500
      ng/cm(2)), was shown to be significantly reduced when applied to clothed skin
      (cotton shirt), regardless of application vehicle (isopropanol (IPA) or propylene
      glycol (PG)). The majority of applied dose was retained within the clothing after
      4 h exposure. Significant reduction in absorption of chlorpyrifos (in PG) was
      seen through clothed skin when supplemented with skin decontamination at 4 h,
      compared with clothed skin decontaminated after 24 h, however, this was not
      observed with IPA. Absorption of dichlorvos (5 MUg/cm(2)) was greater through
      unclothed skin than chlorpyrifos for all vehicles (IPA, isopropyl myristate (IPM)
      and PG). Significant reduction in absorption was observed when decontaminating
      clothed skin at 30 min, compared with decontamination at 24 h (post-exposure) for
      all vehicles. RESULT: indicate that 'every-day' clothing is effective at reducing
      exposure to chemicals in contact with skin. Washing the skin surface immediately
      following removal of exposed clothing can further reduce exposure, depending on
      the properties of the chemical and vehicle applied.

PMID- 24910985
TI  - Single-walled carbon nanotube exposure induces membrane rearrangement and
      suppression of receptor-mediated signalling pathways in model mast cells.
AB  - Carbon nanotubes (CNT) are environmental challenges to the respiratory and
      gastrointestinal mucosa, and to the dermal immune system. Mast cells (MC) are pro
      inflammatory immunocytes that reside at these interfaces with the environment.
      Mast cells are sources of pro-inflammatory mediators (histamine, serotonin,
      matrix-active proteases, eicosanoids, prostanoids, cytokines and chemokines),
      which are released in a calcium-dependent manner following immunological
      challenge or physico-chemical stimulation. Since C-60 fullerenes, which share
      geometry with CNT, are suppressive of mast cell-driven inflammatory responses, we
      explored the effects of unmodified SWCNT aggregates on mast cell signaling
      pathways, phenotype and pro-inflammatory function. We noted SWCNT suppression of
      antigen-induced signalling pathways and pro-inflammatory degranulation responses.
      Mast cells recognize unmodified SWCNT by remodeling the plasma membrane,
      disaggregating the cortical actin cytoskeleton and relocalizing clathrin.
      Clathrin was also identified as a component of an affinity-purified 'interactome'
      isolated from MC using an SWCNT affinity matrix for mast cell lysates. Together,
      these data are consistent with the ability of SWCNT to suppress mast cell pro
      inflammatory function via a novel recognition mechanism. 

PMID- 24910988
TI  - Amino acid-dependent transformations of citrate-coated silver nanoparticles:
      impact on morphology, stability and toxicity.
AB  - Humans face the risk of exposure to silver nanoparticles (AgNPs) due to their
      extensive application in consumer products. AgNPs can interact with many
      substances in the human body due to their chemically unstable nature and high
      activity properties, which might result in unknown hazards and even some serious
      diseases for humans. As the basic constituent element of human bodies, amino
      acids (AAs) differ in concentration and variety in different cells and tissues.
      Thus, understanding the transformation of citrate-coated AgNPs in the presence of
      AAs is crucial for determining their fate and toxicity in the human body. Our
      study focused on the transformation of the morphology, dissolution behavior and
      reaction product of AgNPs in different AA-containing systems and then evaluated
      the effect of these transformations on the cytotoxicity of AgNPs. The obtained
      results indicated that the addition of glycine with the lowest Ag(+) binding
      energy had little effect on the transformations and toxicity of AgNPs. While in
      the presence of histidine with higher Ag(+) binding energy, the Ag(+) release and
      particle size of AgNPs obviously increased. These transformations resulted in a
      decrease in the cytotoxicity of AgNPs due to the formation of Ag-His complex and
      the growth of AgNPs. Furthermore, l-cysteine with the highest Ag(+) binding
      energy could easily interact with AgNPs, transforming them completely to form
      [Ag(Cys)n](+) and Ag2S precipitates, which induced the largest decrease in AgNP
      toxicity. In summary, our results may provide useful information to understand
      the fate, transformation, and toxicity of citrate-coated AgNPs in the human body.

PMID- 24910989
TI  - Percutaneous absorption and distribution of organophosphates (chlorpyrifos and
      dichlorvos) following dermal exposure and decontamination scenarios using in
      vitro human skin model.
AB  - To date, there has been little research investigating low-level human exposure to
      chemicals, and so the aim of this study was to examine the percutaneous
      penetration of organophosphates (dichlorvos and chlorpyrifos) using low-level
      exposure scenarios in vitro. Dermal absorption of chlorpyrifos applied in
      different vehicles was measured at 0, 4, 8 and 24 h, after dose application for 4
      and 24 h exposure (finite dose, 500 ng/cm(2)) in isopropanol (IPA), isopropyl
      myristate (IPM) and propylene glycol (PG). Dichlorvos was applied to the skin for
      24 h (infinite dose, 1 mg/cm(2) and 10 mg/cm(2); finite dose, 5 MUg/cm(2)) using
      the same vehicles. Human skin was mounted in flow through diffusion cells with
      minimum essential medium eagle pH 7.4 (supplemented with 2% BSA) as receptor
      fluid. Following exposure, the skin surface dose was removed by tissue swabbing,
      the stratum corneum removed by sequential tape stripping, and the skin digested
      prior to scintillation counting (chlorpyrifos), or GC/MS analysis (dichlorvos).
      The dermal absorption of chlorpyrifos was the greatest following application in
      PG (19.5% of dose), when compared with absorption from the IPA and IPM vehicles
      (10.3% and 1.9% absorbed respectively). However, dichlorvos showed greater dermal
      absorption than chlorpyrifos from all vehicles used, with greatest absorption
      from the IPA vehicle (38.6% absorbed). Although dichlorvos exhibited a short lag
      time (0.6 h from IPA and IP vehicles, and 0.4 h from PG), chlorpyrifos displayed
      greater propensity to accumulate in the stratum corneum and epidermis/dermis.
      These results demonstrate that prompt skin surface decontamination would be
      required for both dichlorvos and chlorpyrifos (and chemicals with similar
      properties) in the event of skin contact. The magnitude of the skin reservoir
      formed with chlorpyrifos was time dependent, therefore, prompt decontamination of
      this and similar chemicals would be required to reduce delayed systemic
      absorption.

PMID- 24910990
TI  - Analysis of familial hemophagocytic lymphohistiocytosis type 4 (FHL-4) mutant
      proteins reveals that S-acylation is required for the function of syntaxin 11 in
      natural killer cells.
AB  - Natural killer (NK) cell secretory lysosome exocytosis and cytotoxicity are
      impaired in familial hemophagocytic lymphohistiocytosis type 4 (FHL-4), a
      disorder caused by mutations in the gene encoding the SNARE protein syntaxin 11.
      We show that syntaxin 11 binds to SNAP23 in NK cells and that this interaction is
      reduced by FHL-4 truncation and frameshift mutation proteins that delete all or
      part of the SNARE domain of syntaxin 11. In contrast the FHL-4 mutant proteins
      bound to the Sec-1/Munc18-like (SM) protein Munc18-2. We demonstrate that the C
      terminal cysteine rich region of syntaxin 11, which is deleted in the FHL-4
      mutants, is S-acylated. This posttranslational modification is required for the
      membrane association of syntaxin 11 and for its polarization to the immunological
      synapse in NK cells conjugated to target cells. Moreover, we show that Munc18-2
      is recruited by syntaxin 11 to intracellular membranes in resting NK cells and to
      the immunological synapse in activated NK cells. This recruitment of Munc18-2 is
      abolished by deletion of the C-terminal cysteine rich region of syntaxin 11.
      These results suggest a pivotal role for S-acylation in the function of syntaxin
      11 in NK cells. 

PMID- 24910991
TI  - Effect of broccoli sprouts on nasal response to live attenuated influenza virus
      in smokers: a randomized, double-blind study.
AB  - BACKGROUND: Smokers have increased susceptibility and altered innate host defense
      responses to influenza virus infection. Broccoli sprouts are a source of the Nrf2
      activating agentsulforaphane, and short term ingestion of broccoli sprout
      homogenates (BSH) has been shown to reduce nasal inflammatory responses to
      oxidant pollutants. OBJECTIVES: Assess the effects of BSH on nasal cytokines,
      virus replication, and Nrf2-dependent enzyme expression in smokers and
      nonsmokers. METHODS: We conducted a randomized, double-blind, placebo-controlled
      trial comparing the effects of BSH on serially sampled nasal lavage fluid (NLF)
      cytokines, viral sequence quantity, and Nrf2-dependent enzyme expression in NLF
      cells and biopsied epithelium. Healthy young adult smokers and nonsmokers
      ingested BSH or placebo (alfalfa sprout homogenate) for 4 days, designated Days 
      1, 0, 1, 2. On Day 0 they received standard vaccine dose of live attenuated
      influenza virus (LAIV) intranasally. Nasal lavage fluids and nasal biopsies were
      collected serially to assess response to LAIV. RESULTS: In area under curve
      analyses, post-LAIV IL-6 responses (P = 0.03) and influenza sequences (P = 0.01)
      were significantly reduced in NLF from BSH-treated smokers, while NAD(P)H:
      quinoneoxidoreductasein NLF cells was significantly increased. In nonsmokers, a
      similar trend for reduction in virus quantity with BSH did not reach statistical
      significance. CONCLUSIONS: In smokers, short term ingestion of broccoli sprout
      homogenates appears to significantly reduce some virus-induced markers of
      inflammation, as well as reducing virus quantity. Nutritional antioxidant
      interventions have promise as a safe, low-cost strategy for reducing influenza
      risk among smokers and other at risk populations. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01269723.

PMID- 24910992
TI  - EDEM2 and OS-9 are required for ER-associated degradation of non-glycosylated
      sonic hedgehog.
AB  - Misfolded proteins of the endoplasmic reticulum (ER) are eliminated by the ER
      associated degradation (ERAD) in eukaryotes. In S. cerevisiae, ER-resident
      lectins mediate substrate recognition through bipartite signals consisting of an
      unfolded local structure and the adjacent glycan. Trimming of the glycan is
      essential for the directional delivery of the substrates. Whether a similar
      recognition and delivery mechanism exists in mammalian cells is unknown. In this
      study, we systematically study the function and substrate specificity of known
      mammalian ER lectins, including EDEM1/2/3, OS-9 and XTP-3B using the recently
      identified ERAD substrate sonic hedgehog (SHH), a soluble protein carrying a
      single N-glycan, as well as its nonglycosylated mutant N278A. Efficient ERAD of
      N278A requires the core processing complex of HRD1, SEL1L and p97, similar to the
      glycosylated SHH. While EDEM2 was required for ERAD of both glycosylated and non
      glycosylated SHHs, EDEM3 was only necessary for glycosylated SHH and EDEM1 was
      dispensable for both. Degradation of SHH and N278A also required OS-9, but not
      the related lectin XTP3-B. Robust interaction of both EDEM2 and OS-9 with a non
      glycosylated SHH variant indicates that the misfolded polypeptide backbone,
      rather than a glycan signature, functions as the predominant signal for
      recognition for ERAD. Notably, SHH-N278A is the first nonglycosylated substrate
      to require EDEM2 for recognition and targeting for ERAD. EDEM2 also interacts
      with calnexin and SEL1L, suggesting a potential avenue by which misfolded
      glycoproteins may be shunted towards SEL1L and ERAD rather than being released
      into the secretory pathway. Thus, ER lectins participate in the recognition and
      delivery of misfolded ER substrates differently in mammals, with an underlying
      mechanism distinct from that of S. cerevisiae. 

PMID- 24910993
TI  - Response of last instar Helicoverpa armigera larvae to Bt toxin ingestion:
      changes in the development and in the CYP6AE14, CYP6B2 and CYP9A12 gene
      expression.
AB  - Bt crops are able to produce Cry proteins, which were originally present in
      Bacillus thuringiensis bacteria. Although Bt maize is very efficient against corn
      borers, Spanish crops are also attacked by the earworm H. armigera, which is less
      susceptible to Bt maize. Many mechanisms could be involved in this low
      susceptibility to the toxin, including the insect's metabolic resistance to
      toxins due to cytochrome P450 monooxygenases. This paper examines the response of
      last instar H. armigera larvae to feeding on a diet with Bt and non-Bt maize
      leaves in larval development and in the gene expression of three P450
      cytochromes: CYP6AE14, CYP6B2 and CYP9A12. Larvae fed on sublethal amounts of the
      Bt toxin showed reduced food ingestion and reduced growth and weight, preventing
      most of them from achieving the critical weight and pupating; additionally, after
      feeding for one day on the Bt diet the larvae showed a slight increase in
      juvenile hormone II in the hemolymp. Larvae fed on the non-Bt diet showed the
      highest CYP6AE14, CYP6B2 and CYP9A12 expression one day after feeding on the non
      Bt diet, and just two days later the expression decreased abruptly, a finding
      probably related to the developmental programme of the last instar. Moreover,
      although the response of P450 genes to plant allelochemicals and xenobiotics has
      been related in general to overexpression in the resistant insect, or induction
      of the genes when feeding takes place, the expression of the three genes studied
      was suppressed in the larvae feeding on the Bt toxin. The unexpected inhibitory
      effect of the Cry1Ab toxin in the P450 genes of H. armigera larvae should be
      thoroughly studied to determine whether this response is somehow related to the
      low susceptibility of the species to the Bt toxin. 

PMID- 24910995
TI  - Physiological and morphological responses of Ischaemum rugosum Salisb. (wrinkled
      grass) to different nitrogen rates and rice seeding rates.
AB  - Ischaemum rugosum is a competitive weed in direct-seeded rice systems. Developing
      integrated weed management strategies that promote the suppression of weeds by
      crop density, cultivar selection, and nutrition requires better understanding of
      the extent to which rice interferes with the growth of this weed and how it
      responds to resource limitation due to rice interference. The growth of I.
      rugosum was studied when grown with four rice seeding rates (0, 25, 50, and 100
      kg ha(-1)) and four nitrogen (N) rates (0, 50, 100, and 150 kg ha(-1)). Compared
      to the weed plants grown alone, weed tiller number was reduced by 63-80%, leaf
      number by 68-77%, leaf area by 69-77%, leaf biomass by 72-84%, and inflorescence
      biomass by 81-93% at the rice seeding rates of 25-100 kg ha(-1). All these
      parameters increased with increasing rates of N from 0 to 150 kg ha(-1). At weed
      maturity, I. rugosum plants were 100% taller than rice at 0 kg N ha(-1), whereas,
      with added N, the weeds were only 50% taller than rice. Weed biomass increased by
      82-160%, whereas rice biomass increased by 92-229%, with the application of 50
      150 kg N ha(-1). Added N favored rice biomass production more than it did the
      weed. Rice interference reduced the height and biomass of I. rugosum, but did not
      suppress its growth completely. I. rugosum showed the ability to reduce the
      effects of rice interference by increasing leaf area, leaf weight ratio, and
      specific leaf area, and by decreasing the root-shoot weight ratio in comparison
      to the weed plants grown alone. The results suggest that rice crop interference
      alone may reduce I. rugosum growth but may not provide complete control of this
      weed. The need for integrated weed management practices to effectively control
      this weed species is highlighted.

PMID- 24910996
TI  - Inactivation of the nucleus accumbens core or medial shell attenuates
      reinstatement of sugar-seeking behavior following sugar priming or exposure to
      food-associated cues.
AB  - Re-exposure to either palatable food or to conditioned stimuli associated with
      food is known to reinstate food-seeking after periods of abstinence. The nucleus
      accumbens core and shell are important for reinstatement in both food- and drug
      seeking paradigms, although their potential differential roles have been
      difficult to delineate due to methodological differences in paradigms across
      laboratories. The present studies assessed the effects of temporary inactivation
      of the core or shell on priming- and cue-induced reinstatement of food-seeking in
      identically-trained rats. Inactivation of either the nucleus accumbens core
      (Experiment 1A; N = 10) or medial shell (Experiment 1B; N = 12) blocked priming
      induced reinstatement in an equivalent manner. Similarly, inactivation of the
      core or medial shell (Experiments 2A & 2B; N = 11 each) also blocked cue-induced
      reinstatement, although there was also a significant treatment day X brain region
      X drug order interaction. Specifically, rats with core inactivation reinstated
      lever-pressing on the vehicle injection day regardless of whether that was their
      first or second test, whereas rats that had medial shell inactivation on the
      first day did not significantly reinstate lever-pressing on the second day of
      testing (when they received vehicle). Yohimbine, while a reportedly robust
      pharmacological stressor, was ineffective at inducing reinstatement in the
      current stress-induced reinstatement procedure. These data suggest that both the
      nucleus accumbens core and shell serve important roles in reinstatement of food
      seeking in response to priming and cues. 

PMID- 24910997
TI  - Liver stiffness value-based risk estimation of late recurrence after curative
      resection of hepatocellular carcinoma: development and validation of a predictive
      model.
AB  - BACKGROUND: Preoperative liver stiffness (LS) measurement using transient
      elastography (TE) is useful for predicting late recurrence after curative
      resection of hepatocellular carcinoma (HCC). We developed and validated a novel
      LS value-based predictive model for late recurrence of HCC. METHODS: Patients who
      were due to undergo curative resection of HCC between August 2006 and January
      2010 were prospectively enrolled and TE was performed prior to operations by
      study protocol. The predictive model of late recurrence was constructed based on
      a multiple logistic regression model. Discrimination and calibration were used to
      validate the model. RESULTS: Among a total of 139 patients who were finally
      analyzed, late recurrence occurred in 44 patients, with a median follow-up of
      24.5 months (range, 12.4-68.1). We developed a predictive model for late
      recurrence of HCC using LS value, activity grade II-III, presence of multiple
      tumors, and indocyanine green retention rate at 15 min (ICG R15), which showed
      fairly good discrimination capability with an area under the receiver operating
      characteristic curve (AUROC) of 0.724 (95% confidence intervals [CIs], 0.632
      0.816). In the validation, using a bootstrap method to assess discrimination, the
      AUROC remained largely unchanged between iterations, with an average AUROC of
      0.722 (95% CIs, 0.718-0.724). When we plotted a calibration chart for predicted
      and observed risk of late recurrence, the predicted risk of late recurrence
      correlated well with observed risk, with a correlation coefficient of 0.873
      (P<0.001). CONCLUSION: A simple LS value-based predictive model could estimate
      the risk of late recurrence in patients who underwent curative resection of HCC.

PMID- 24910998
TI  - The natural chemopreventive agent sulforaphane inhibits STAT5 activity.
AB  - Signal transducer and activator of transcription STAT5 is an essential mediator
      of cytokine, growth factor and hormone signaling. While its activity is tightly
      regulated in normal cells, its constitutive activation directly contributes to
      oncogenesis and is associated to a number of hematological and solid tumor
      cancers. We previously showed that deacetylase inhibitors can inhibit STAT5
      transcriptional activity. We now investigated whether the dietary chemopreventive
      agent sulforaphane, known for its activity as deacetylase inhibitor, might also
      inhibit STAT5 activity and thus could act as a chemopreventive agent in STAT5
      associated cancers. We describe here sulforaphane (SFN) as a novel STAT5
      inhibitor. We showed that SFN, like the deacetylase inhibitor trichostatin A
      (TSA), can inhibit expression of STAT5 target genes in the B cell line Ba/F3, as
      well as in its transformed counterpart Ba/F3-1*6 and in the human leukemic cell
      line K562 both of which express a constitutively active form of STAT5. Similarly
      to TSA, SFN does not alter STAT5 initial activation by phosphorylation or binding
      to the promoter of specific target genes, in favor of a downstream
      transcriptional inhibitory effect. Chromatin immunoprecipitation assays revealed
      that, in contrast to TSA however, SFN only partially impaired the recruitment of
      RNA polymerase II at STAT5 target genes and did not alter histone H3 and H4
      acetylation, suggesting an inhibitory mechanism distinct from that of TSA.
      Altogether, our data revealed that the natural compound sulforaphane can inhibit
      STAT5 downstream activity, and as such represents an attractive cancer
      chemoprotective agent targeting the STAT5 signaling pathway. 

PMID- 24910999
TI  - Association of branched-chain amino acids with carotid intima-media thickness and
      coronary artery disease risk factors.
AB  - BACKGROUND: Recent studies have determined that branched-chain (BCAAs) and
      aromatic (AAAs) amino acids are strongly correlated with obesity and atherogenic
      dyslipidemia and are strong predictors of diabetes. However, it is not clear if
      these amino acids are capable of identifying subjects with coronary artery
      disease (CAD), particularly with subclinical atherosclerosis who are at risk of
      developing CAD. METHODS: Four hundred and seventy two Chinese subjects (272 males
      and 200 females, 42-97 y of age) undergoing physical exams were recruited at
      random for participation in the cross-sectional study. Serum BCAAs and AAAs were
      measured using our previously reported isotope dilution liquid chromatography
      tandem mass spectrometry method. Bilateral B-mode carotid artery images for
      carotid intima-media thickness (cIMT) were acquired at end diastole and cIMT
      values more than 0.9 mm were categorized as increased. Correlations of BCAAs with
      cIMT and other CAD risk factors were analyzed. RESULTS: BCAAs and AAAs were
      significantly and positively associated with risk factors of CAD, e.g., cIMT,
      BMI, waist circumference, blood pressure, fasting blood glucose, TG, apoB,
      apoB/apoAI ratio, apoCII, apoCIII and hsCRP, and were significantly and
      negatively associated with HDL-C and apoAI. Stepwise multiple linear regression
      analysis revealed that age (beta = 0.175, P<0.001), log BCAA (beta = 0.147,
      P<0.001) and systolic blood pressure (beta = 0.141, P = 0.012) were positively
      and independently associated with cIMT. In the logistic regression model, the
      most and only powerful laboratory factor correlated with increased cIMT was BCAA
      (the odds ratio of the fourth quartile compared to the first quartile was 2.679;
      P = 0.009). CONCLUSION: BCAAs are independently correlated with increased cIMT.
      This correlation would open a new field of research in the mechanistic
      understanding and risk assessment of CAD.

PMID- 24911000
TI  - Fingolimod attenuates splenocyte-induced demyelination in cerebellar slice
      cultures.
AB  - The family of sphingosine-1-phosphate receptors (S1PRs) is G-protein-coupled,
      comprised of subtypes S1PR1-S1PR5 and activated by the endogenous ligand S1P. The
      phosphorylated version of Fingolimod (pFTY720), an oral therapy for multiple
      sclerosis (MS), induces S1PR1 internalisation in T cells, subsequent
      insensitivity to S1P gradients and sequestering of these cells within lymphoid
      organs, thus limiting immune response. S1PRs are also expressed in neuronal and
      glial cells where pFTY720 is suggested to directly protect against lysolecithin
      induced deficits in myelination state in organotypic cerebellar slices. Of note,
      the effect of pFTY720 on immune cells already migrated into the CNS, prior to
      treatment, has not been well established. We have previously found that
      organotypic slice cultures do contain immune cells, which, in principle, could
      also be regulated by pFTY720 to maintain levels of myelin. Here, a mouse
      organotypic cerebellar slice and splenocyte co-culture model was thus used to
      investigate the effects of pFTY720 on splenocyte-induced demyelination. Spleen
      cells isolated from myelin oligodendrocyte glycoprotein immunised mice (MOG
      splenocytes) or from 2D2 transgenic mice (2D2-splenocytes) both induced
      demyelination when co-cultured with mouse organotypic cerebellar slices, to a
      similar extent as lysolecithin. As expected, in vivo treatment of MOG-immunised
      mice with FTY720 inhibited demyelination induced by MOG-splenocytes. Importantly,
      in vitro treatment of MOG- and 2D2-splenocytes with pFTY720 also attenuated
      demyelination caused by these cells. In addition, while in vitro treatment of 2D2
      splenocytes with pFTY720 did not alter cell phenotype, pFTY720 inhibited the
      release of the pro-inflammatory cytokines such as interferon gamma (IFNgamma) and
      interleukin 6 (IL6) from these cells. This work suggests that treatment of
      splenocytes by pFTY720 attenuates demyelination and reduces pro-inflammatory
      cytokine release, which likely contributes to enhanced myelination state induced
      by pFTY720 in organotypic cerebellar slices. 

PMID- 24911002
TI  - A functional transient receptor potential vanilloid 4 (TRPV4) channel is
      expressed in human endothelial progenitor cells.
AB  - Endothelial progenitor cells (EPCs) are mobilized into circulation to replace
      damaged endothelial cells and recapitulate the vascular network of injured
      tissues. Intracellular Ca(2+) signals are key to EPC activation, but it is yet to
      be elucidated whether they are endowed with the same blend of Ca(2+) -permeable
      channels expressed by mature endothelial cells. For instance, endothelial colony
      forming cells (ECFCs), the only EPC subset truly committed to acquire a mature
      endothelial phenotype, lack canonical transient receptor potential channels 3, 5
      and 6 (TRPC3, 5 and 6), which are widely distributed in vascular endothelium; on
      the other hand, they express a functional store-operated Ca(2+) entry (SOCE). The
      present study was undertaken to assess whether human circulating EPCs possess TRP
      vanilloid channel 4 (TRPV4), which plays a master signalling role in mature
      endothelium, by controlling both vascular remodelling and arterial pressure. We
      found that EPCs express both TRPV4 mRNA and protein. Moreover, both GSK1016790A
      (GSK) and phorbol myristate acetate and, two widely employed TRPV4 agonists,
      induced intracellular Ca(2+) signals uniquely in presence of extracellular
      Ca(2+). GSK- and PMA-induced Ca(2+) elevations were inhibited by RN-1734 and
      ruthenium red, which selectively target TRPV4 in mature endothelium. However,
      TRPV4 stimulation with GSK did not cause EPC proliferation, while the
      pharmacological blockade of TRPV4 only modestly affected EPC growth in the
      presence of a growth factor-enriched culture medium. Conversely, SOCE inhibition
      with BTP-2, La(3+) and Gd(3+) dramatically decreased cell proliferation. These
      data indicate that human circulating EPCs possess a functional TRPV4 protein
      before their engraftment into nascent vessels.

PMID- 24911003
TI  - Environmental tobacco smoke exposure and children's intelligence at 8-11 years of
      age.
AB  - BACKGROUND: Evidence supporting a link between postnatal environmental tobacco
      smoke (ETS) exposure and cognitive problems among children is mounting, but
      inconsistent. OBJECTIVES: We examined the relationship between ETS exposure,
      measured using urine cotinine, and IQ scores in Korean school-aged children.
      METHODS: The participants were 996 children 8-11 years of age recruited from five
      administrative regions in South Korea. We performed a cross-sectional analysis of
      urinary cotinine concentrations and IQ scores obtained using the abbreviated form
      of a Korean version of the Wechsler Intelligence Scales for Children.
      Associations were adjusted for potential confounders, and estimates were derived
      with and without adjustment for mother's Full-Scale IQ (FSIQ) score. RESULTS:
      After adjusting for sociodemographic and developmental covariates, urinary
      cotinine concentrations were inversely associated with FSIQ, Verbal IQ (VIQ),
      Performance IQ (PIQ), vocabulary, math, and block design scores. Following
      further adjustment for maternal IQ, only the VIQ scores remained significantly
      associated with urinary cotinine concentration (B = -0.31; 95% CI: -0.60, -0.03
      for a 1-unit increase in natural log-transformed urine cotinine concentration; p
      = 0.03). CONCLUSION: Urine cotinine concentrations were inversely associated with
      children's VIQ scores before and after adjusting for maternal IQ. Further
      prospective studies with serial measurements of cotinine are needed to confirm
      our findings.

PMID- 24911004
TI  - Arguments, more than confidence, explain the good performance of reasoning
      groups.
AB  - In many intellective tasks groups consistently outperform individuals. One factor
      is that the individual(s) with the best answer is able to convince the other
      group members using sound argumentation. Another factor is that the most
      confident group member imposes her answer whether it is right or wrong. In
      Experiments 1 and 2, individual participants were given arguments against their
      answer in intellective tasks. Demonstrating sound argumentative competence, many
      participants changed their minds to adopt the correct answer, even though the
      arguments had no confidence markers, and barely any participants changed their
      minds to adopt an incorrect answer. Confidence could not explain who changed
      their mind, as the least confident participants were as likely to change their
      minds as the most confident. In Experiments 3 (adults) and 4 (10-year-olds),
      participants solved intellective tasks individually and then in groups, before
      solving transfer problems individually. Demonstrating again sound argumentative
      competence, participants adopted the correct answer when it was present in the
      group, and many succeeded in transferring this understanding to novel problems.
      Moreover, the group member with the right answer nearly always managed to
      convince the group even when she was not the most confident. These results show
      that argument quality can overcome confidence among the factors influencing the
      discussion of intellective tasks. Explanations for apparent exceptions are
      discussed.

PMID- 24911005
TI  - Polyphosphate goes from pedestrian to prominent in the marine P-cycle.

PMID- 24911006
TI  - Phylogenetic evidence for a mild H1 pandemic in the early 1900s.

PMID- 24911007
TI  - Neurons that keep a straight face.

PMID- 24911009
TI  - Evaluation of a pooled strategy for high-throughput sequencing of cosmid clones
      from metagenomic libraries.
AB  - High-throughput sequencing methods have been instrumental in the growing field of
      metagenomics, with technological improvements enabling greater throughput at
      decreased costs. Nonetheless, the economy of high-throughput sequencing cannot be
      fully leveraged in the subdiscipline of functional metagenomics. In this area of
      research, environmental DNA is typically cloned to generate large-insert
      libraries from which individual clones are isolated, based on specific activities
      of interest. Sequence data are required for complete characterization of such
      clones, but the sequencing of a large set of clones requires individual barcode
      based sample preparation; this can become costly, as the cost of clone barcoding
      scales linearly with the number of clones processed, and thus sequencing a large
      number of metagenomic clones often remains cost-prohibitive. We investigated a
      hybrid Sanger/Illumina pooled sequencing strategy that omits barcoding
      altogether, and we evaluated this strategy by comparing the pooled sequencing
      results to reference sequence data obtained from traditional barcode-based
      sequencing of the same set of clones. Using identity and coverage metrics in our
      evaluation, we show that pooled sequencing can generate high-quality sequence
      data, without producing problematic chimeras. Though caveats of a pooled strategy
      exist and further optimization of the method is required to improve recovery of
      complete clone sequences and to avoid circumstances that generate unrecoverable
      clone sequences, our results demonstrate that pooled sequencing represents an
      effective and low-cost alternative for sequencing large sets of metagenomic
      clones. 

PMID- 24911008
TI  - High prevalence of skin diseases and need for treatment in a middle-aged
      population. A Northern Finland Birth Cohort 1966 study.
AB  - To determine the overall prevalence of skin diseases a whole-body skin
      examination was performed for 1,932 members (46-years of age) of the Northern
      Finland Birth Cohort (NFBC 1966), which is a comprehensive longitudinal research
      program (N = 12,058). A high prevalence of all skin diseases needing treatment
      was found (N = 1,158). Half of the cases of skin findings were evaluated to be
      serious enough to require diagnostic evaluation, treatment or follow-up either in
      a general health care, occupational health care or a secondary care setting. The
      remaining half were thought to be slight and self-treatment was advised. Males
      (70%) had more skin diseases needing treatment than females (52%) (P<0.001). The
      most common skin finding was a benign skin tumor, which was found in every cohort
      member. Skin infections (44%), eczemas (27%) and sebaceous gland diseases (27%)
      were the most common skin diseases in the cohort. Moreover, skin infections and
      eczemas were more commonly seen in the group with low education compared to those
      with high education (P<0.005). The results strengthen the postulate that skin
      diseases are common in an adult population. 

PMID- 24911011
TI  - Judging joint angles and movement outcome: Shifting the focus of attention in
      dart-throwing.
AB  - Many research studies have shown the advantage of an external focus of attention
      (FOA) relative to an internal focus for motor learning and performance when the
      focus is explicitly instructed. The current experiments varied the FOA by asking
      the participants to judge either joint angles (internal probes) or spatial
      accuracy (external probes) following dart throws in which vision was removed. The
      probes were administered without prior practice (Experiment 1) or following 432
      practice trials (Experiment 2). Spatial errors and trial-to-trial variability
      were reduced in Experiment 2 compared with Experiment 1. In both experiments,
      spatial errors were greater during internal probes compared with external probes
      or a no-probe control condition. These data suggest that the advantages of an
      external FOA relative to an internal FOA are not fully attributable to visual
      processing and that these advantages can be attained using probing questions
      between trials, whereas previous research has explicitly instructed the FOA.

PMID- 24911010
TI  - Use of Internet viral marketing to promote smoke-free lifestyles among Chinese
      adolescents.
AB  - PURPOSE: Youth smoking is a global public health concern. Health educators are
      increasingly using Internet-based technologies, but the effectiveness of Internet
      viral marketing in promoting health remains uncertain. This prospective pilot
      study assessed the efficacy of an online game-based viral marketing campaign in
      promoting a smoke-free attitude among Chinese adolescents. METHODS: One hundred
      and twenty-one Hong Kong Chinese adolescents aged 10 to 24 were invited to
      participate in an online multiple-choice quiz game competition designed to
      deliver tobacco-related health information. Participants were encouraged to refer
      others to join. A zero-inflated negative binomial model was used to explore the
      factors contributing to the referral process. Latent transition analysis
      utilising a pre- and post-game survey was used to detect attitudinal changes
      toward smoking. RESULTS: The number of participants increased almost eightfold
      from 121 to 928 (34.6% current or ex-smokers) during the 22-day campaign.
      Participants exhibited significant attitudinal change, with 73% holding negative
      attitudes toward smoking after the campaign compared to 57% before it. The
      transition probabilities from positive to negative and neutral to negative
      attitudes were 0.52 and 0.48, respectively. It was also found that attempting
      every 20 quiz questions was associated with lower perceived smoking decision in
      future (OR = 0.95, p-value <0.01). CONCLUSIONS: Our online game-based viral
      marketing programme was effective in reaching a large number of smoking and non
      smoking participants and changing their attitudes toward smoking. It constitutes
      a promising practical and cost-effective model for engaging young smokers and
      promulgating smoking-related health information among Chinese adolescents.

PMID- 24911012
TI  - Scaling up perception-action links: Evidence from synchronization with individual
      and joint action.
AB  - How do we map joint actions we participate in onto joint actions we observe
      others performing, such as when a couple dancing tango observes another couple
      dancing tango? We investigated this question using a task in which participants
      were instructed to perform individual or joint movements in synchrony with
      individual or joint movements observed on a computer screen. The observed
      movements started slowly and then continuously increased in tempo (from 1.75 Hz
      to 3 Hz). The results showed that, with regard to spatial parameters, joint
      performance was more accurate when observing joint action than when observing
      individual action (Experiments 1, 1a, and 1b). Individual performance was more
      accurate when observing individual action than when observing joint action
      (Experiments 3 and 4). There were no systematic differences with regard to timing
      parameters. These results suggest that mechanisms of temporal coordination may be
      less susceptible to differences between individual and joint action than
      mechanisms of spatial matching.

PMID- 24911013
TI  - When speech sounds like music.
AB  - Repetition can boost memory and perception. However, repeating the same stimulus
      several times in immediate succession also induces intriguing perceptual
      transformations and illusions. Here, we investigate the Speech to Song
      Transformation (S2ST), a massed repetition effect in the auditory modality, which
      crosses the boundaries between language and music. In the S2ST, a phrase repeated
      several times shifts to being heard as sung. To better understand this unique
      cross-domain transformation, we examined the perceptual determinants of the S2ST,
      in particular the role of acoustics. In 2 Experiments, the effects of 2 pitch
      properties and 3 rhythmic properties on the probability and speed of occurrence
      of the transformation were examined. Results showed that both pitch and rhythmic
      properties are key features fostering the transformation. However, some
      properties proved to be more conducive to the S2ST than others. Stable tonal
      targets that allowed for the perception of a musical melody led more often and
      quickly to the S2ST than scalar intervals. Recurring durational contrasts arising
      from segmental grouping favoring a metrical interpretation of the stimulus also
      facilitated the S2ST. This was, however, not the case for a regular beat
      structure within and across repetitions. In addition, individual perceptual
      abilities allowed to predict the likelihood of the S2ST. Overall, the study
      demonstrated that repetition enables listeners to reinterpret specific prosodic
      features of spoken utterances in terms of musical structures. The findings
      underline a tight link between language and music, but they also reveal important
      differences in communicative functions of prosodic structure in the 2 domains.

PMID- 24911014
TI  - Differential time scales of change to learning frequency structures of isometric
      force tracking.
AB  - Multiple processes support the persistent (learning) and transient (adaptive)
      change in behavior over time. We investigated whether practice and rest influence
      similarly the learning and adaptation of slow and fast frequency structures in
      isometric force tracking of pathways that varied in their regularity.
      Participants practiced 25 trials on each of 5 days in either a constant force
      target or 1 with the 1/f distributional properties of brown or pink noise. There
      was a reduction in root mean squared error (RMSE) as well as an increasing
      positive correlation between force output and the target pathway for all noise
      conditions over days. The spectral frequency analysis of force output and RMSE
      revealed task dependent outcomes of learning and adaptation as a function of the
      relatively slow (0-4 Hz) and fast (8-12 Hz) oscillatory time scales. These
      contrasting findings show that the persistent and transient properties of
      learning occur across different timescales and dimensions of behavior (force
      output and outcome-RMSE).

PMID- 24911015
TI  - beta3-Adrenoreceptor stimulation protects against myocardial infarction injury
      via eNOS and nNOS activation.
AB  - beta3-adrenergic receptor (AR) and the downstream signaling, nitric oxide
      synthase (NOS) isoforms, have been emerged as novel modulators of heart function
      and even potential therapeutic targets for cardiovascular diseases. However, it
      is not known whether beta3-AR plays cardioprotective effects against myocardial
      infarction (MI) injury. Therefore, the present study was designed to determine
      the effects of beta3-AR on MI injury and to elucidate the underlying mechanism.
      MI model was constructed by left anterior descending (LAD) artery ligation.
      Animals were administrated with beta3-AR agonist BRL37344 (BRL) or beta3-AR
      inhibitor SR59230A (SR) respectively at 0.1 mg/kg/hour one day after MI
      operation. The scar area, cardiac function and the apoptosis of myocardial were
      assessed by Masson's trichrome stain, echocardiography and TUNEL assay
      respectively. Western blot analysis was performed to elucidate the expressions of
      target proteins. beta3-AR activation with BRL administration significantly
      attenuated fibrosis and decreased scar area after MI. Moreover, BRL also
      preserved heart function, and reduced the apoptosis of cardiomyocyte induced by
      MI. Furthermore, BRL treatment altered the phosphorylation status of endothelial
      NOS (eNOS) and increased the expression of neuronal NOS (nNOS). These results
      suggested that beta3-AR stimulation has a substantial effect on recovery of heart
      function. In addition, the activations of both eNOS and nNOS may be associated
      with the cardiac protective effects of beta3-AR. 

PMID- 24911016
TI  - Neural correlates associated with successful working memory performance in older
      adults as revealed by spatial ICA.
AB  - To investigate which neural correlates are associated with successful working
      memory performance, fMRI was recorded in healthy younger and older adults during
      performance on an n-back task with varying task demands. To identify functional
      networks supporting working memory processes, we used independent component
      analysis (ICA) decomposition of the fMRI data. Compared to younger adults, older
      adults showed a larger neural (BOLD) response in the more complex (2-back) than
      in the baseline (0-back) task condition, in the ventral lateral prefrontal cortex
      (VLPFC) and in the right fronto-parietal network (FPN). Our results indicated
      that a higher BOLD response in the VLPFC was associated with increased
      performance accuracy in older adults, in the more complex task condition. This
      'BOLD-performance' relationship suggests that the neural correlates linked with
      successful performance in the older adults are related to specific working memory
      processes present in the complex but not in the baseline task condition
      [corrected].Furthermore, the selective presence of this relationship in older but
      not in younger adults suggests that increased neural activity in the VLPFC serves
      a compensatory role in the aging brain which benefits task performance in the
      elderly.

PMID- 24911017
TI  - Driving: a road to unhealthy lifestyles and poor health outcomes.
AB  - BACKGROUND: Driving is a common part of modern society, but its potential effects
      on health are not well understood. PURPOSE: The present cross-sectional study (n
      = 37,570) examined the associations of driving time with a series of health
      behaviors and outcomes in a large population sample of middle-aged and older
      adults using data from the Social, Economic, and Environmental Factor Study
      conducted in New South Wales, Australia, in 2010. METHODS: Multiple logistic
      regression was used in 2013 to examine the associations of usual daily driving
      time with health-related behaviors (smoking, alcohol use, diet, physical
      activity, sedentary behavior, sleep) and outcomes (obesity, general health,
      quality of life, psychological distress, time stress, social functioning),
      adjusted for socio-demographic characteristics. RESULTS: Findings suggested that
      longer driving time was associated with higher odds for smoking, insufficient
      physical activity, short sleep, obesity, and worse physical and mental health.
      The associations consistently showed a dose-response pattern and more than 120
      minutes of driving per day had the strongest and most consistent associations
      with the majority of outcomes. CONCLUSION: This study highlights driving as a
      potential lifestyle risk factor for public health. More population-level
      multidisciplinary research is needed to understand the mechanism of how driving
      affects health.

PMID- 24911019
TI  - Correlates of low physical activity levels in aging men and women: the DR's EXTRA
      Study (ISRCTN45977199).
AB  - Recognizing correlates of low physical activity (PA) can help in targeting PA
      interventions for individuals who would benefit most from increasing their PA. We
      studied the associations of demographic, social, health, and lifestyle factors
      with low PA by sex in a population sample of 1,303 Finnish individuals aged 57-78
      years. We defined low PA as no moderate or vigorous leisure-time PA reported in
      an interview. Altogether, 39% of men and 48% of women reported low PA.
      Satisfactory or poor perceived health and high BMI were independently associated
      with low PA in both sexes. In men, factors such as age, being divorced or
      separated, still working, having a weak social network, poor diet, and a health
      professional's suggestion to increase PA were associated with low PA. In women,
      cardiovascular disease and depressive symptoms were associated with low PA. These
      results can be applied in targeting PA interventions. 

PMID- 24911020
TI  - New pediatric vision screener employing polarization-modulated, retinal
      birefringence-scanning-based strabismus detection and bull's eye focus detection
      with an improved target system: opto-mechanical design and operation.
AB  - Amblyopia ("lazy eye") is a major public health problem, caused by misalignment
      of the eyes (strabismus) or defocus. If detected early in childhood, there is an
      excellent response to therapy, yet most children are detected too late to be
      treated effectively. Commercially available vision screening devices that test
      for amblyopia's primary causes can detect strabismus only indirectly and
      inaccurately via assessment of the positions of external light reflections from
      the cornea, but they cannot detect the anatomical feature of the eyes where
      fixation actually occurs (the fovea). Our laboratory has been developing
      technology to detect true foveal fixation, by exploiting the birefringence of the
      uniquely arranged Henle fibers delineating the fovea using retinal birefringence
      scanning (RBS), and we recently described a polarization-modulated approach to
      RBS that enables entirely direct and reliable detection of true foveal fixation,
      with greatly enhanced signal-to-noise ratio and essentially independent of
      corneal birefringence (a confounding variable with all polarization-sensitive
      ophthalmic technology). Here, we describe the design and operation of a new
      pediatric vision screener that employs polarization-modulated, RBS-based
      strabismus detection and bull's eye focus detection with an improved target
      system, and demonstrate the feasibility of this new approach.

PMID- 24911018
TI  - Patterns of leisure-time physical activity participation in a British birth
      cohort at early old age.
AB  - Using data from a nationally representative British birth cohort we characterized
      the type and diversity of leisure-time physical activity that 2,188 participants
      (age 60-64 years) engaged in throughout the year by gender and obesity.
      Participants most commonly reported walking (71%), swimming (33%), floor
      exercises (24%) and cycling (15%). Sixty-two percent of participants reported >=
      2 activities in the past year and 40% reported diversity on a regular basis.
      Regular engagement in different types of activity (cardio-respiratory,
      balance/flexibility and strength) was reported by 67%, 19% and 11% of
      participants, respectively. We found gender differences, as well as differences
      by obesity status, in the activities reported, the levels of activity diversity
      and activity type. Non-obese participants had greater activity diversity, and
      more often reported activities beneficial for cardio-respiratory health and
      balance/flexibility than obese participants. These findings may be used to inform
      the development of trials of physical activity interventions targeting older
      adults, and those older adults with high body mass index.

PMID- 24911021
TI  - Sensitivity correction for the influence of the fat layer on muscle oxygenation
      and estimation of fat thickness by time-resolved spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) has been used for noninvasive assessment of
      oxygenation in living tissue. For muscle measurements by NIRS, the measurement
      sensitivity to muscle (S(M)) is strongly influenced by fat thickness (FT). In
      this study, we investigated the influence of FT and developed a correction curve
      for S(M) with an optode distance (3 cm) sufficiently large to probe the muscle.
      First, we measured the hemoglobin concentration in the forearm (n=36) and thigh
      (n=6) during arterial occlusion using a time-resolved spectroscopy (TRS) system,
      and then FT was measured by ultrasound. The correction curve was derived from the
      ratio of partial mean optical path length of the muscle layer <L(M)> to observed
      mean optical path length <L>. There was good correlation between FT and <L> at
      rest, and <L> could be used to estimate FT. The estimated FT was used to validate
      the correction curve by measuring the forearm blood flow (FBF) by strain-gauge
      plethysmography (SGP_FBF) and TRS (TRS_FBF) simultaneously during a reactive
      hyperemia test with 16 volunteers. The corrected TRS_FBF results were similar to
      the SGP_FBF results. This is a simple method for sensitivity correction that does
      not require use of ultrasound.

PMID- 24911022
TI  - White feces syndrome of shrimp arises from transformation, sloughing and
      aggregation of hepatopancreatic microvilli into vermiform bodies superficially
      resembling gregarines.
AB  - Accompanying acute hepatopancreatic necrosis disease (AHPND) in cultivated Asian
      shrimp has been an increasing prevalence of vermiform, gregarine-like bodies
      within the shrimp hepatopancreas (HP) and midgut. In high quantity they result in
      white fecal strings and a phenomenon called white feces syndrome (WFS). Light
      microscopy (LM) of squash mounts and stained smears from fresh HP tissue revealed
      that the vermiform bodies are almost transparent with widths and diameters
      proportional to the HP tubule lumens in which they occur. Despite vermiform
      appearance, they show no cellular structure. At high magnification (LM with 40
      100x objectives), they appear to consist of a thin, outer membrane enclosing a
      complex of thicker, inter-folded membranes. Transmission electron microscopy
      (TEM) revealed that the outer non-laminar membrane of the vermiform bodies bore
      no resemblance to a plasma membrane or to the outer layer of any known gregarine,
      other protozoan or metazoan. Sub-cellular organelles such as mitochondria,
      nuclei, endoplasmic reticulum and ribosomes were absent. The internal membranes
      had a tubular sub-structure and occasionally enclosed whole B-cells, sloughed
      from the HP tubule epithelium. These internal membranes were shown to arise from
      transformed microvilli that peeled away from HP tubule epithelial cells and then
      aggregated in the tubule lumen. Stripped of microvilli, the originating cells
      underwent lysis. By contrast, B-cells remained intact or were sloughed
      independently and whole from the tubule epithelium. When sometimes engulfed by
      the aggregated, transformed microvilli (ATM) they could be misinterpreted as cyst
      like structures by light microscopy, contributing to gregarine-like appearance.
      The cause of ATM is currently unknown, but formation by loss of microvilli and
      subsequent cell lysis indicate that their formation is a pathological process. If
      sufficiently severe, they may retard shrimp growth and may predispose shrimp to
      opportunistic pathogens. Thus, the cause of ATM and their relationship (if any)
      to AHPND should be determined. 

PMID- 24911023
TI  - The impact of the wavelet propagation distribution on SEIRS modeling with delay.
AB  - Previous models of disease spread involving delay have used basic SIR
      (susceptible--infectious--recovery) formulae and approaches. This paper
      demonstrates how time-varying SEIRS (S--exposed--I - R - S) models can be
      extended with delay to produce wave propagations that simulate periodic wave
      fronts of disease spread in the context of population movements. The model also
      takes into account the natural mortality associated with the disease spread.
      Understanding the delay of an infectious disease is critical when attempting to
      predict where and how fast the disease will propagate. We use cellular automata
      to model the delay and its effect on the spread of infectious diseases where
      population movement occurs. We illustrate an approach using wavelet transform
      analysis to understand the impact of the delay on the spread of infectious
      diseases. The results indicate that including delay provides novel ways to
      understand the effects of migration and population movement on disease spread.

PMID- 24911024
TI  - Fucoidan can function as an adjuvant in vivo to enhance dendritic cell maturation
      and function and promote antigen-specific T cell immune responses.
AB  - Fucoidan, a sulfated polysaccharide purified from brown algae, has a variety of
      immune-modulation effects, including promoting antigen uptake and enhancing anti
      viral and anti-tumor effects. However, the effect of fucoidan in vivo, especially
      its adjuvant effect on in vivo anti-tumor immune responses, was not fully
      investigated. In this study, we investigated the effect of fucoidan on the
      function of spleen dendritic cells (DCs) and its adjuvant effect in vivo.
      Systemic administration of fucoidan induced up-regulation of CD40, CD80 and CD86
      expression and production of IL-6, IL-12 and TNF-alpha in spleen cDCs. Fucoidan
      also promoted the generation of IFN-gamma-producing Th1 and Tc1 cells in an IL-12
      dependent manner. When used as an adjuvant in vivo with ovalbumin (OVA) antigen,
      fucoidan promoted OVA-specific antibody production and primed IFN-gamma
      production in OVA-specific T cells. Moreover, fucoidan enhanced OVA-induced up
      regulation of MHC class I and II on spleen cDCs and strongly prompted the
      proliferation of OVA-specific CD4 and CD8 T cells. Finally, OVA immunization with
      fucoidan as adjuvant protected mice from the challenge with B16-OVA tumor cells.
      Taken together, these results suggest that fucoidan can function as an adjuvant
      to induce Th1 immune response and CTL activation, which may be useful in tumor
      vaccine development. 

PMID- 24911026
TI  - Relationships between 25-hydroxyvitamin D and nocturnal enuresis in five- to
      seven-year-old children.
AB  - BACKGROUND: Vitamin D has been recognized to contribute to various physiological
      processes. However, no study has investigated serum 25-hydroxyvitamin D [25(OH)D]
      concentrations in children with nocturnal enuresis (NE) in the English
      literature. OBJECTIVE: In the present study, serum 25(OH)D concentrations were
      measured in five- to seven-year-old children with NE and compared with those in
      non-enuretic children to investigate whether there was any relationship between
      25(OH)D and NE as the first time in the literature. DESIGN: Two hundred forty
      seven five- to seven-year-old children were recruited from Taizhou, Zhejiang
      Province, China. Serum 25(OH)D concentrations were measured, and the structured
      questionnaire was administered to the parents of all children. Low 25(OH)D was
      defined as serum 25(OH)D concentrations below 20 ng/ml. RESULTS: The prevalence
      of NE was 7.3% in the group of children with 25(OH)D concentrations that exceeded
      20 ng/ml; this prevalence was much lower than the 17.5% observed in the group of
      children with 25(OH)D concentrations below 20 ng/ml (p<0.05). After adjusting for
      potential confounders, serum 25(OH)D (>=20 ng/ml) was significantly associated
      with NE and represented a protective factor against NE (OR = 0.31, 95%CI = 0.092,
      1.0, P<0.05). A nonlinear relationship between 25(OH)D and NE was observed. The
      prevalence of NE decreased with increasing 25(OH)D concentrations above 19 ng/ml.
      Additionally, children exhibiting higher frequencies of bedwetting had lower
      25(OH)D concentrations [5-7 times/week: 18.3+/-4.8; 2-4 times/week: 20.9+/-4.1; 0
      1 times/week: 23.6+/-6.4 (ng/ml), P<0.05)]. CONCLUSIONS: Low 25(OH)D was
      associated with an increased risk of NE in children aged five to seven years.

PMID- 24911025
TI  - Prognostic value of blood flow measurements using arterial spin labeling in
      gliomas.
AB  - The period of event-free survival (EFS) within the same histopathological glioma
      grades may have high variability, mainly without a known cause. The purpose of
      this study was to reveal the prognostic value of quantified tumor blood flow
      (TBF) values obtained by arterial spin labeling (ASL) for EFS in patients with
      histopathologically proven astrocytomas independent of WHO (World Health
      Organization) grade. Twenty-four patients with untreated gliomas underwent tumor
      perfusion quantification by means of pulsed ASL in 3T. The clinical history of
      the patients was retrospectively extracted from the local database. Six patients
      had to be excluded due to insufficent follow-up data for further evaluation or
      histopathologically verified oligodendroglioma tumor components. Receiver
      operating characteristic (ROC) curves were used to define an optimal cut-off
      value of maximum TBF (mTBF) values for subgrouping in low-perfused and high
      perfused gliomas. Kaplan-Meier curves and Cox proportional hazard regression
      model were used to determine the prognostic value of mTBF for EFS. An optimal
      mTBF cut-off value of 182 ml/100 g/min (sensitivity  = 83%, specificity  = 100%)
      was determined. Patients with low-perfused gliomas had significantly longer EFS
      compared to patients with high-perfused gliomas (p = 0.0012) independent of the
      WHO glioma grade. Quantified mTBF values obtained by ASL offer a new and totally
      non-invasive marker to prognosticate the EFS, independently on histopathological
      tumor grading, in patients with gliomas. 

PMID- 24911027
TI  - The unresolved role of cardiotocography (CTG), fetal ECG (STAN) and intrapartum
      fetal pulse oximetry (IFPO) as diagnostic methods for fetal hypoxia.

PMID- 24911028
TI  - Multisite, randomized, double-blind, placebo-controlled pilot clinical trial to
      evaluate the efficacy of buspirone as a relapse-prevention treatment for cocaine
      dependence.
AB  - OBJECTIVE: To evaluate the potential efficacy of buspirone as a relapse
      prevention treatment for cocaine dependence. METHOD: A randomized, double-blind,
      placebo-controlled, 16-week pilot trial was conducted at 6 clinical sites between
      August 2012 and June 2013. Adult crack cocaine users meeting DSM-IV-TR criteria
      for current cocaine dependence who were scheduled to be in inpatient/residential
      substance use disorder (SUD) treatment for 12-19 days when randomized and
      planning to enroll in local outpatient treatment through the end of the active
      treatment phase were randomized to buspirone titrated to 60 mg/d (n = 35) or
      placebo (n = 27). All participants received psychosocial treatment as usually
      provided by the SUD treatment programs in which they were enrolled. Outcome
      measures included maximum days of continuous cocaine abstinence (primary),
      proportion of cocaine use days, and days to first cocaine use during the
      outpatient treatment phase (study weeks 4-15) as assessed by self-report and
      urine drug screens. RESULTS: There were no significant treatment effects on
      maximum continuous days of cocaine abstinence or days to first cocaine use. In
      the female participants (n = 23), there was a significant treatment-by-time
      interaction effect (chi21 = 15.26, P < .0001), reflecting an increase in cocaine
      use by those receiving buspirone, relative to placebo, early in the outpatient
      treatment phase. A similar effect was not detected in the male participants (n =
      39; chi21 = 0.14, P = .70). CONCLUSIONS: The results suggest that buspirone is
      unlikely to have a beneficial effect on preventing relapse to cocaine use and
      that buspirone for cocaine-dependent women may worsen their cocaine use outcomes.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01641159.

PMID- 24911030
TI  - Knowledge, attitudes and practices of breast cancer screening among women in
      Jordan.
AB  - Enhancing breast cancer screening in developing countries is pivotal in improving
      women's health. We aimed at describing knowledge of and perceived reasons for
      performing breast cancer screening. We interviewed 1,549 population-based
      randomly selected women. We found that women share limited knowledge about breast
      cancer screening. Few women performed screening for early detection purposes. The
      influence of physicians was the main reason for performing mammography.
      Prevalence of breast cancer screening might be enhanced by integrating screening
      into other medical services. Health agencies need to invite women for screening
      and educate them regarding the importance of screening in the absence of
      symptoms. 

PMID- 24911029
TI  - Infection cycle of Artichoke Italian latent virus in tobacco plants: meristem
      invasion and recovery from disease symptoms.
AB  - Nepoviral infections induce recovery in fully expanded leaves but persist in
      shoot apical meristem (SAM) by a largely unknown mechanism. The dynamics of
      infection of a grapevine isolate of Artichoke Italian latent virus (AILV-V, genus
      Nepovirus) in tobacco plants, including colonization of SAM, symptom induction
      and subsequent recovery of mature leaves from symptoms, were characterized. AILV
      V moved from the inoculated leaves systemically and invaded SAM in 7 days post
      inoculation (dpi), remaining detectable in SAM at least up to 40 dpi. The new top
      leaves recovered from viral symptoms earliest at 21 dpi. Accumulation of viral
      RNA to a threshold level was required to trigger the overexpression of RDR6 and
      DCL4. Consequently, accumulation of viral RNA decreased in the systemically
      infected leaves, reaching the lowest concentration in the 3rd and 4th leaves at
      23 dpi, which was concomitant with recovery of the younger, upper leaves from
      disease symptoms. No evidence of virus replication was found in the recovered
      leaves, but they contained infectious virus particles and were protected against
      re-inoculation with AILV-V. In this study we also showed that AILV-V did not
      suppress initiation or maintenance of RNA silencing in transgenic plants, but was
      able to interfere with the cell-to-cell movement of the RNA silencing signal. Our
      results suggest that AILV-V entrance in SAM and activation of RNA silencing may
      be distinct processes since the latter is triggered in fully expanded leaves by
      the accumulation of viral RNA above a threshold level rather than by virus
      entrance in SAM. 

PMID- 24911031
TI  - Confronting inadvertent stigma and pejorative language in addiction scholarship:
      a recognition and response.
AB  - Appropriate use of language in the field of addiction is important. Inappropriate
      use of language can negatively impact the way society perceives substance use and
      the people who are affected by it. Language frames what the public thinks about
      substance use and recovery, and it can also affect how individuals think about
      themselves and their own ability to change. But most importantly, language
      intentionally and unintentionally propagates stigma: the mark of dishonor,
      disgrace, and difference that depersonalizes people, depriving them of individual
      or personal qualities and personal identity. Stigma is harmful, distressing, and
      marginalizing to the individuals, groups, and populations who bear it. For these
      reasons, the Editorial Team of Substance Abuse seeks to formally operationalize
      respect for personhood in our mission, our public relations, and our instructions
      to authors. We ask authors, reviewers, and readers to carefully and intentionally
      consider the language used to describe alcohol and other drug use and disorders,
      the individuals affected by these conditions, and their related behaviors,
      comorbidities, treatment, and recovery in our publication. Specifically, we make
      an appeal for the use of language that (1) respects the worth and dignity of all
      persons ("people-first language"); (2) focuses on the medical nature of substance
      use disorders and treatment; (3) promotes the recovery process; and (4) avoids
      perpetuating negative stereotypes and biases through the use of slang and idioms.
      In this paper, we provide a brief overview of each of the above principles, along
      with examples, as well as some of the nuances and tensions that inherently arise
      as we give greater attention to the issue of how we talk and write about
      substance use and addiction.

PMID- 24911032
TI  - Reversible switching of electronic ground state in a pentacoordinated Cu(II) 1D
      cationic polymer and structural diversity.
AB  - Two copper(II) polymeric complexes {[Cu(HPymat)(MeOH)](NO3)}n (1) and
      {[Cu4(Pymab)4(H2O)4](NO3)4} (2) were synthesized with the carboxylate-containing
      Schiff-base ligands HPymat(-) and Pymab(-) [H2Pymat = (E)-2-(1-(pyridin-2
      yl)methyleneamino)terephthalic acid, HPymab = (E)-2-((pyridine-2
      yl)methyleneamino)benzoic acid]. Complex 1 is a one-dimensional Cu(II) cationic
      polymeric complex containing free protonated carboxylic groups and nitrate anions
      as counterions. Complex 2 is a zero-dimensional tetranuclear cationic Cu(II)
      complex containing nitrate anions as counterions. Complex 1 shows rhombic
      electron paramagnetic resonance (EPR) spectra in the solid state at room
      temperature (RT) and 77 K and tetragonal EPR spectra in dimethyl sulfoxide (DMSO)
      and dimethylformamide (DMF) and "inverse" EPR spectrum in CH3CN. Complex 2 shows
      rhombic EPR spectra in the solid state at RT and 77 K. But complex 2 shows
      tetragonal spectra in DMSO, DMF, and CH3CN. Thermogravimetric analysis was also
      performed for both complexes 1 and 2. Mean-square displacement amplitude analysis
      was carried out to detect librational disorder along the metal-ligand bonds in
      crystal structures. 

PMID- 24911033
TI  - Patient engagement during medical visits and smoking cessation counseling.
AB  - IMPORTANCE: Increased patient engagement with health and health care is
      considered crucial to increasing the quality of health care and patient self
      management of health. OBJECTIVE: To examine whether patients with high levels of
      engagement during medical encounters are more likely to receive advice and
      counseling about smoking compared with less engaged patients. DESIGN, SETTING,
      AND PARTICIPANTS: Cross-sectional survey using multivariate regression analysis
      of 8656 current and retired autoworkers and their spouses younger than 65 years
      who are or were employed by the 3 major US auto companies. MAIN OUTCOMES AND
      MEASURES: Clinician advice and counseling about smoking; patients who tried to
      quit smoking. RESULTS: Among 1904 current smokers, 58.5% of those who were more
      highly engaged during medical encounters were counseled by clinicians about
      specific strategies and methods to stop smoking, compared with 45.4% of patients
      who were less engaged. Patient engagement and being advised by clinicians to stop
      smoking had independent effects on smoking cessation efforts by patients.
      Accounting for differences in other patient characteristics, patients with high
      engagement levels were more likely to try to stop smoking compared with patients
      with lower engagement (odds ratio, 1.62; P < .01). Patients who were both highly
      engaged and had received counseling from clinicians were the most likely to try
      to stop smoking (74.6%) while patients with low engagement who did not receive
      counseling were the least likely (46.0%). Nevertheless, counseling is still
      effective among even less engaged patients; 60.4% of smokers with low engagement
      who received counseling tried to quit smoking in the past year compared with
      46.0% who did not receive counseling. CONCLUSIONS AND RELEVANCE: The study
      results provide evidence that clinicians respond differently to patients who are
      highly engaged during medical encounters than they do to less engaged patients in
      terms of smoking cessation advice. Clinicians should not assume that low patient
      engagement and greater passivity during medical encounters is evidence of
      unwillingness to quit. The results show that smoking cessation counseling is
      associated with a higher likelihood of quit attempts even for patients who are
      less engaged during medical encounters.

PMID- 24911034
TI  - Effect of oronasopharyngeal suction on arterial oxygen saturation in normal, term
      infants delivered vaginally: a prospective randomised controlled trial.
AB  - Oronasopharyngeal suction (ONPS) with a suction bulb at birth is a traditional
      practice in the initial management of healthy infants in Iran and many other
      countries. The purpose of this study was to compare the effects of
      oronasopharyngeal suction (ONPS) with those of no suction in normal, term
      newborns delivered vaginally. A total of 170 healthy term infants of first and
      single uncomplicated pregnancies, with clear amniotic fluid, vaginal delivery and
      cephalic presentation, enrolled in the trial during labour. Newborns were
      randomised into one of the two groups, according to the use of the ONPS
      procedure. Arterial oxygen saturation (SaO2) levels, heart rates, blood gases of
      umbilical cord and Apgar scores were determined. The mean SaO2 values over the
      first and fifth min of birth were similar in the two groups. The maximum time to
      reach SaO2 of >= 92% was shorter in the no suction group. There were no
      statistically significant differences in the mean of heart rates, respiratory
      rates and Apgar scores between the groups. Apgar scores at 5 and 10 min were
      between 8 and 10 for all infants, respectively. Newborns receiving suction showed
      a statistically significant, lower mean partial carbon dioxide pressure (PCO2)
      and a significantly higher partial oxygen pressure (PO2) of umbilical artery.
      Although the differences were statistically significant, these were not
      considered clinically significant because values remained within normal ranges.
      According to this study, ONPS is not recommended as a routine procedure in
      normal, term infants delivered vaginally.

PMID- 24911035
TI  - Differences in chronic intragraft inflammation between positive crossmatch and
      ABO-incompatible kidney transplantation.
AB  - BACKGROUND: ABO-incompatible kidney transplantations (ABOiKTxs) seem to have
      better long-term outcomes than positive crossmatch kidney transplantations
      (+XMKTxs). METHODS: This study aimed to assess the differences in chronic injury
      on histologic findings on 1- and 5-year surveillance biopsies and the clinical
      outcomes in living-donor kidney transplantations performed between May 1999 and
      November 2006 including 102 +XMKTxs, 73 ABOiKTxs, and 652 conventional KTxs.
      RESULTS: Although 5-year patient survival was similar between groups, graft loss
      between 1 and 5 years was similar in ABOiKTx (2.6% per year) and conventional KTx
      (1.7% per yr), and both were lower than that of +XMKTx (5.8% per year). At 5
      years, renal function was similar in ABOiKTx and conventional KTx, and both were
      higher than that of +XMKTx, which had higher rates of inflammation and chronic
      glomerulopathy on both 1- and 5-year biopsies. Despite having evidence of less
      chronic injury, ABOiKTx showed a higher rate of intragraft complement activation
      (C4d deposition) at 5 years compared with +XMKTx (77.8% vs. 18.9%, P<0.001).
      CONCLUSION: These data suggest that +XMKTxs have high rates of chronic
      inflammation at 1 and 5 years after transplantation, which may explain the higher
      rates of graft loss and lower renal function compared with other factors such as
      anti-donor antibody or intragraft complement deposition.

PMID- 24911036
TI  - B-sides serologic markers of immunogenicity in kidney transplanted patients:
      report from 2012-2013 flu vaccination experience.
AB  - BACKGROUND: Safety and immunogenicity data of seasonal influenza vaccination in
      transplanted patients (Tps) are controversial. Preexisting cross-reactive
      antibodies generated by repeated vaccination with drift variant strains could
      bias interpretation of immunogenicity data in Tp. METHODS: The unadjuvanted 2012
      2013 seasonal influenza vaccine was administered to 81 kidney Tps being routinely
      vaccinated against influenza and 23 healthy controls (HCs). Immunogenicity was
      evaluated by both strain-specific antibody responses with standard
      hemagglutination inhibition assay and by memory B-cell enzyme-linked
      immunosorbent spot. Safety was also evaluated by measuring anti-human leukocyte
      antigen (HLA) antibodies. RESULTS: The majority of Tps were seroprotected before
      vaccination (81.5%, 81.5%, and 43.2% vs. 47.8%, 34.8%, and 30.4% in HC for H1N1,
      H3N2, and B strain, respectively) resulting into lower seroconversion rates
      (P<=0.01) as compared with HC (40.7%, 39.5%, and 54.3% vs. 73.9%, 82.6%, and
      65.2% for H1N1, H3N2, and B strain, respectively). An inverse correlation was
      found between seroconversion rates and number of previous vaccinations in Tps. On
      the contrary, similar increase in the frequencies of strain-specific memory B
      cells were detected by B-cell enzyme-linked immunosorbent spot in both Tps and
      HCs after vaccination. No serious adverse events have been reported. Donor
      specific HLA antibodies increased in two patients after vaccination, and de novo
      anti-HLA antibodies were identified in two additional patients (non-donor
      specific HLA antibodies). CONCLUSION: This report on safety and immunogenicity of
      the seasonal unadjuvanted 2012-2013 flu vaccination suggests that evaluating
      immunogenicity of influenza vaccination exclusively by hemagglutination
      inhibition assay may be misleading in individuals receiving yearly seasonal
      vaccines. Further investigations are required to understand the relation between
      vaccination and anti-HLA antibody development.

PMID- 24911037
TI  - Single-donor islet transplantation and long-term insulin independence in select
      patients with type 1 diabetes mellitus.
AB  - BACKGROUND: Islet transplantation is a recognized treatment option for select
      patients with type I diabetes mellitus. However, islet infusions from multiple
      donors are often required to achieve insulin independence. Ideally, insulin
      independence would be achieved routinely with only a single donor. Identification
      of factors associated with insulin independence after single-donor islet
      transplantation may help to select recipient-donor combinations with the highest
      probability of success. METHODS: Subjects undergoing islet transplantation at a
      single center (Edmonton, Canada) between March 1999 and August 2013 were
      included. Recipient, donor, and transplant characteristics were collected and
      compared between recipients who became insulin independent after one islet
      transplantation and those who did not. RESULTS: Thirty-one patients achieved
      insulin independence after a single-donor islet transplantation, and 149 did not.
      Long-term insulin-free survival was not different between the groups. Factors
      significantly associated with single-donor success included recipient age,
      insulin requirement at baseline, donor weight, donor body mass index, islet
      transplant mass, and peritransplant heparin and insulin administration. On
      multivariate analysis, pretransplantation daily insulin requirements, the use of
      peritransplantation heparin and insulin infusions, and islet transplant mass
      remained significant. CONCLUSION: We have identified clinically relevant
      differences defining the achievement of insulin independence after single-donor
      transplantation. Based on these differences, a preoperative insulin requirement
      of less than 0.6 U/kg per day and receiving more than 5,646 islet equivalents
      (IEQ)/kg have a sensitivity of 84% and 71% and specificity of 50% and 50%,
      respectively, for insulin independence after single-donor islet transplantation.
      With ideal patient selection, this finding could potentially increase single
      donor transplantation success and may be especially relevant for presensitized
      subjects or those who may subsequently require renal replacement.

PMID- 24911038
TI  - Effects of obesity on kidney transplantation outcomes: a systematic review and
      meta-analysis.
AB  - BACKGROUND: The effects of obesity on outcomes reported after kidney
      transplantation have been controversial. The purpose of this systematic review
      and meta-analysis was to elucidate this issue. METHODS: MEDLINE, EMBASE, Cochrane
      Library, and gray literature were searched up to August 6, 2013. Studies that
      compared obese and nonobese patients who underwent kidney transplantation and
      evaluated one of these outcomes-delayed graft function (DGF), acute rejection,
      graft or patient survival at 1 or 5 years after transplantation, or death by
      cardiovascular disease (CVD)-were included. Two independent reviewers extracted
      the data and assessed the quality of the studies. RESULTS: From 1,973 articles
      retrieved, 21 studies (9,296 patients) were included. Obesity was associated with
      DGF (relative risk, 1.41; 95% confidence interval, 1.26-1.57; I=8%;
      Pheterogeneity=0.36), but not with acute rejection. Graft loss and death were
      associated with obesity only in the analysis of studies that evaluated patients
      who received a kidney graft before year 2000. No association of obesity with
      graft loss and death was found in the analysis of studies that evaluated patients
      who received a kidney graft after year 2000. Death by CVD was associated with
      obesity (relative risk, 2.07; 95% confidence interval, 1.17-3.64; I=0%;
      Pheterogeneity=0.59); however, most studies included in this analysis evaluated
      patients who received a kidney graft after year 2000. CONCLUSION: In conclusion,
      obese patients have increased risk for DGF. In the past years, obesity was a risk
      factor for graft loss, death by CVD, and all-cause mortality. However, for the
      obese transplanted patient today, the graft and patient survival is the same as
      that of the nonobese patient.

PMID- 24911039
TI  - Changes in successive measures of de novo donor-specific anti-human leukocyte
      antigen antibodies intensity and the development of allograft dysfunction.
AB  - BACKGROUND: Many patients develop de novo donor-specific anti-human leukocyte
      antigen antibodies (dnDSA) after transplantation. Despite development of dnDSA,
      not all patients will immediately fail. This study analyzes dnDSA intensity and
      longitudinal trends as prospective clinical parameters to assess subsequent
      allograft function. METHODS: Twenty-four patients with dnDSA onset in the first 2
      years after transplantation received antibody monitoring by LABScreen single
      antigen beads. Estimated glomerular filtration rate (eGFR) was recorded at time
      of dnDSA onset and up to 24 months thereafter. The dnDSA mean fluorescence
      intensity (MFI) of the stable function patient group (n=8; eGFR decline <= 25%)
      was compared with the impaired function patient group (n=16; eGFR decline>25%)
      using first year peak MFI (pMFI), eight month MFI change (DeltaMFI), and eighteen
      month MFI trend (MFI slope). RESULTS: Both groups showed similar dnDSA
      characteristics (time to onset after transplantation, class I/II distribution,
      and initial MFI). Between groups, MFI trends were analyzed. Impaired patients
      showed a higher pMFI during the first year (median pMFI, 13,055 vs. 2,397;
      P=0.007). Longitudinal analysis revealed that DeltaMFI was strongly associated
      with dysfunction. Both a DeltaMFI increase greater than 20% as well as a stronger
      increase (DeltaMFI>50%) were followed by graft dysfunction in almost all patients
      and could significantly differentiate between stable and impaired function
      patients (P=0.001 and P=0.04, respectively). CONCLUSION: Our study suggests that
      tracking dnDSA intensity, particularly in the early period after onset, is
      important to estimate the impact of dnDSA on the allograft and could, therefore,
      determine help on how best to monitor patients with dnDSA.

PMID- 24911040
TI  - Influence of Number of Contact Efforts on Running Performance During Game-Based
      Activities.
AB  - PURPOSE: To determine the influence the number of contact efforts during a single
      bout has on running intensity during game-based activities and assess
      relationships between physical qualities and distances covered in each game.
      METHODS: Eighteen semiprofessional rugby league players (age 23.6 +/- 2.8 y)
      competed in 3 off-side small-sided games (2 * 10-min halves) with a contact bout
      performed every 2 min. The rules of each game were identical except for the
      number of contact efforts performed in each bout. Players performed 1, 2, or 3 *
      5-s wrestles in the single-, double-, and triple-contact game, respectively. The
      movement demands (including distance covered and intensity of exercise) in each
      game were monitored using global positioning system units. Bench-press and back
      squat 1-repetition maximum and the 30-15 Intermittent Fitness Test (30-15IFT)
      assessed muscle strength and high-intensity-running ability, respectively.
      RESULTS: There was little change in distance covered during the single-contact
      game (ES = -0.16 to -0.61), whereas there were larger reductions in the double-
      (ES = -0.52 to -0.81) and triple-contact (ES = -0.50 to -1.15) games. Significant
      relationships (P < .05) were observed between 30-15IFT and high-speed running
      during the single- (r = .72) and double- (r = .75), but not triple-contact (r =
      .20) game. CONCLUSIONS: There is little change in running intensity when only
      single contacts are performed each bout; however, when multiple contacts are
      performed, greater reductions in running intensity result. In addition, high
      intensity-running ability is only associated with running performance when
      contact demands are low.

PMID- 24911041
TI  - What influences contraceptive behaviour in women who experience unintended
      pregnancy? A systematic review of qualitative research.
AB  - One in five pregnancies in the UK ends in abortion. The great majority of those
      pregnancies are unintended, resulting from incorrect, inconsistent or non-use of
      contraception, rather than contraception failure. We undertook a synthesis of
      qualitative research with women who have unintended pregnancies as a new approach
      to understanding contraceptive behaviour. A literature search was carried out
      using four databases. Identified studies were screened against pre-set inclusion
      criteria. Included studies were quality assessed. Analysis followed a meta
      ethnographic approach. A total of 236 studies were identified, of which nine were
      included. Six categories involved in contraceptive behaviour were identified -
      access, method factors, knowledge, societal influence, personal beliefs and
      motivations and relationship factors. A model of contraceptive behaviour was
      developed. Contraceptive behaviour is a complex, multifactorial process.
      Interventions targeting one aspect are unlikely to make a difference; however
      identifying and affecting the important factors within a population may improve
      contraception adherence.

PMID- 24911042
TI  - Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6
      axis in human gastric adenocarcinoma AGS cells.
AB  - Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has
      been reported to possess anticancer activity in many human cancer cells. However,
      the effect of escin on the metastasis has not been studied. The present study
      examined the effect of escin on the migration and invasion of AGS human gastric
      cancer cells. To examine the effects of escin on metastatic capacities of gastric
      cancer cells, AGS cells were cultured in the presence of 0-4 MUmol/L escin. Escin
      inhibited cell migration and invasion in AGS cells. However, escin did not affect
      the viability of these cells at these concentrations. The chemokine receptor and
      its ligands play an important role in cancer metastasis. Escin decreased the
      production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression
      of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6
      was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced
      migration inhibition. In addition, escin inhibited the phosphorylation of focal
      adhesion kinase and Akt. These results demonstrate that escin inhibited the
      migration and invasion of AGS cells, which is associated with altered
      CXCL16/CXCR6 axis. These findings suggest that escin has potential as an
      antimetastatic agent in gastric cancer.

PMID- 24911043
TI  - Molecular Karyotyping of a Dysmorphic Girl from Saudi Arabia with CYP1B1-negative
      Primary Congenital Glaucoma.
AB  - PURPOSE: To report the results of molecular karyotyping for a dysmorphic girl
      with CYP1B1-negative primary congenital glaucoma from Saudi Arabia, where CYPB1
      mutations account for over 90% of cases of primary congenital glaucoma and the
      remaining cases are idiopathic. METHODS: CYP1B1 sequencing in the affected child;
      high-resolution array comparative genomic hybridization (array CGH) of the
      affected child and both unaffected parents (Affymetrix Cytogenetics Whole-Genome
      2.7M array; Affymetrix Inc., Santa Clara, CA, USA). RESULTS: The girl did not
      harbor CYP1B1 mutation by Sanger sequencing. Array CGH revealed 2 de novo 7p
      heterozygous duplications (7p21 - 7p14, encompassing 223 genes, and 7p14-7p11.2,
      encompassing 225 genes) and a 4p homozygous microdeletion (4p14) encompassing one
      gene only, DTHD1. CONCLUSIONS: The fact that this dysmorphic girl is Saudi
      Arabian and has CYP1B1-negative primary congenital glaucoma suggests that her
      glaucoma phenotype is related to her de novo copy number variation. Loss or gain
      of one or more of the genes encompassed in the identified chromosomal areas may
      be associated with primary congenital glaucoma and/or other observed phenotypic
      features.

PMID- 24911044
TI  - Surfactant-induced ordering and wetting transitions of droplets of thermotropic
      liquid crystals "caged" inside partially filled polymeric capsules.
AB  - We report a study of the wetting and ordering of thermotropic liquid crystal (LC)
      droplets that are trapped (or "caged") within micrometer-sized cationic polymeric
      microcapsules dispersed in aqueous solutions of surfactants. When they were
      initially dispersed in water, we observed caged, nearly spherical droplets of E7,
      a nematic LC mixture, to occupy ~40% of the interior volume of the polymeric
      capsules [diameter of 6.7 +/- 0.3 MUm, formed via covalent layer-by-layer
      assembly of branched polyethylenimine and poly(2-vinyl-4,4-dimethylazlactone)]
      and to contact the interior surface of the capsule wall at an angle of ~157 +/-
      11 degrees . The internal ordering of LC within the droplets corresponded to the
      so-called bipolar configuration (distorted by contact with the capsule walls).
      While the effects of dodecyltrimethylammonium bromide (DTAB) and sodium dodecyl
      sulfate (SDS) on the internal ordering of "free" LC droplets are similar, we
      observed the two surfactants to trigger strikingly different wetting and
      configurational transitions when LC droplets were caged within polymeric
      capsules. Specifically, upon addition of SDS to the aqueous phase, we observed
      the contact angles (theta) of caged LC on the interior surface of the capsule to
      decrease, resulting in a progression of complex droplet shapes, including lenses
      (theta ~ 130 +/- 10 degrees ), hemispheres (theta ~ 89 +/- 5 degrees ), and
      concave hemispheres (theta < 85 degrees ). The wetting transitions induced by SDS
      also resulted in changes in the internal ordering of the LC to yield states
      topologically equivalent to axial and radial configurations. Although
      topologically equivalent to free droplets, the contributions that surface
      anchoring, LC elasticity, and topological defects make to the free energy of
      caged LC droplets differ from those of free droplets. Overall, these results and
      others reported herein lead us to conclude that caged LC droplets offer a
      platform for new designs of LC-droplet-based responsive soft matter that cannot
      be realized in dispersions of free droplets. 

PMID- 24911045
TI  - Acid hydrolysis of crude tannins from infructescence of Platycarya strobilacea
      Sieb. et Zucc to produce ellagic acid.
AB  - The infructescence of Platycarya strobilacea Sieb. et Zucc is a well-known
      traditional medicine in China, Japan and Korea. The infructescence of P.
      strobilacea Sieb. et Zucc is a rich source of ellagitannins that are composed of
      ellagic acid (EA) and gallic acid, linked to a sugar moiety. The aim of this
      study was to prepare EA by acid hydrolysis of crude tannins from the
      infructescence of P. strobilacea Sieb. et Zucc, and establish a new technological
      processing method for EA. The natural antioxidant EA was prepared by using the
      water extraction of infructescence of P. strobilacea Sieb. et Zucc, evaporation,
      condensation, acid hydrolysis and prepared by the process of crystallisation. The
      yield percentage of EA from crude EA was more than 20% and the purity of the
      product was more than 98%, as identified by using HPLC. The structure was
      identified on the basis of spectroscopic analysis and comparison with authentic
      compound. 

PMID- 24911046
TI  - Nanopropellers and their actuation in complex viscoelastic media.
AB  - Tissue and biological fluids are complex viscoelastic media with a nanoporous
      macromolecular structure. Here, we demonstrate that helical nanopropellers can be
      controllably steered through such a biological gel. The screw-propellers have a
      filament diameter of about 70 nm and are smaller than previously reported
      nanopropellers as well as any swimming microorganism. We show that the nanoscrews
      will move through high-viscosity solutions with comparable velocities to that of
      larger micropropellers, even though they are so small that Brownian forces
      suppress their actuation in pure water. When actuated in viscoelastic hyaluronan
      gels, the nanopropellers appear to have a significant advantage, as they are of
      the same size range as the gel's mesh size. Whereas larger helices will show very
      low or negligible propulsion in hyaluronan solutions, the nanoscrews actually
      display significantly enhanced propulsion velocities that exceed the highest
      measured speeds in Newtonian fluids. The nanopropellers are not only promising
      for applications in the extracellular environment but small enough to be taken up
      by cells. 

PMID- 24911047
TI  - Perceived coach-created and peer-created motivational climates and their
      associations with team cohesion and athlete satisfaction: evidence from a
      longitudinal study.
AB  - In this longitudinal study, we examined the extent to which perceived coach- and
      peer-created motivational climates are associated with athlete-group cohesion and
      satisfaction with participation among Spanish soccer players competing in the
      Third National Division. Multilevel modelling analyses showed that perceived
      coach-created task climate was positively related to perceived cohesion and
      players' satisfaction with their participation within their team. Also, perceived
      peer-created task climate related positively to perceived cohesion. The results
      indicate the importance of considering peer-related aspects of the motivational
      climate in addition to considering the coach-related aspects of the motivational
      climate when examining motivational group dynamics in sport.

PMID- 24911048
TI  - Clustering and photochemistry of freon CF2Cl2 on argon and ice nanoparticles.
AB  - The photochemistry of CF2Cl2 molecules deposited on argon and ice nanoparticles
      was investigated. The clusters were characterized via electron ionization mass
      spectrometry, and the photochemistry was revealed by the Cl fragment velocity map
      imaging after the CF2Cl2 photodissociation at 193 nm. The complex molecular beam
      experiment was complemented by ab initio calculations. The (CF2Cl2)n clusters
      were generated in a coexpansion with Ar buffer gas. The photodissociation of
      molecules in the (CF2Cl2)n clusters yields predominantly Cl fragments with zero
      kinetic energy: caging. The CF2Cl2 molecules deposited on large argon clusters in
      a pickup experiment are highly mobile and coagulate to form the (CF2Cl2)n
      clusters on ArN. The photodissociation of the CF2Cl2 molecules and clusters on
      ArN leads to the caging of the Cl fragment. On the other hand, the CF2Cl2
      molecules adsorbed on the (H2O)N ice nanoparticles do not form clusters, and no
      Cl fragments are observed from their photodissociation. Since the CF2Cl2 molecule
      was clearly adsorbed on (H2O)N, the missing Cl signal is interpreted in terms of
      surface orientation, possibly via the so-called halogen bond and/or embedding of
      the CF2Cl2 molecule on the disordered surface of the ice nanoparticles. 

PMID- 24911050
TI  - Credentialing high school psychology teachers.
AB  - The National Standards for High School Psychology Curricula (American
      Psychological Association, 2013b) require a teacher with considerable psychology
      content knowledge to teach high school psychology courses effectively. In this
      study, I examined the initial teaching credential requirements for high school
      psychology teachers in the 50 states plus the District of Columbia. Thirty-four
      states (the District of Columbia is included as a state) require the social
      studies credential to teach high school psychology. An analysis of the items on
      standardized tests used by states to validate the content knowledge required to
      teach social studies indicates little or no presence of psychology, a reflection
      of psychology's meager presence in the social studies teacher preparation
      curricula. Thus, new teachers with the social studies teaching credential are not
      prepared to teach high school psychology according to the National Standards.
      Approval of The College, Career, and Civic Life (C3) Framework for Social Studies
      State Standards: Guidance for Enhancing the Rigor of K-12 Civics, Economics,
      Geography, and History (National Council for the Social Studies, 2013) presents
      an opportunity to advocate for establishing a psychology credential in the 34
      states.

PMID- 24911049
TI  - New evidence about language and cognitive development based on a longitudinal
      study: hypotheses for intervention.
AB  - We review findings from a four-year longitudinal study of language learning
      conducted on two samples: a sample of typically developing children whose parents
      vary substantially in socioeconomic status, and a sample of children with pre- or
      perinatal brain injury. This design enables us to study language development
      across a wide range of language learning environments and a wide range of
      language learners. We videotaped samples of children's and parents' speech and
      gestures during spontaneous interactions at home every four months, and then we
      transcribed and coded the tapes. We focused on two behaviors known to vary across
      individuals and environments-child gesture and parent speech-behaviors that have
      the potential to index, and perhaps even play a role in creating, differences
      across children in linguistic and other cognitive skills. Our observations have
      led to four hypotheses that have promise for the development of diagnostic tools
      and interventions to enhance language and cognitive development and brain
      plasticity after neonatal injury. One kind of hypothesis involves tools that
      could identify children who may be at risk for later language deficits. The other
      involves interventions that have the potential to promote language development.
      We present our four hypotheses as a summary of the findings from our study
      because there is scientific evidence behind them and because this evidence has
      the potential to be put to practical use in improving education.

PMID- 24911051
TI  - Osteopontin (OPN) is an important protein to mediate improvements in the
      biocompatibility of C ion-implanted silicone rubber.
AB  - Medical device implants are drawing increasing amounts of interest from modern
      medical practitioners. However, this attention is not evenly spread across all
      such devices; most of these implantable devices can cause adverse reactions such
      as inflammation, fibrosis, thrombosis, and infection. In this work, the
      biocompatibility of silicone rubber (SR) was improved through carbon (C) ion
      implantation. Scanning electron microscopy (SEM), atomic force microscopy (AFM),
      X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) results
      confirmed that these newly generated carbon-implanted silicone rubbers (C-SRs)
      had large, irregular peaks and deep valleys on their surfaces. The water contact
      angle of the SR surface decreased significantly after C ion implantation. C ion
      implantation also changed the surface charge distribution, silicone oxygen rate,
      and chemical-element distribution of SR to favor cell attachment. The dermal
      fibroblasts cultured on the surface C-SR grew faster and showed more typical
      fibroblastic shapes. The expression levels of major adhesion proteins, including
      talin-1, zyxin, and vinculin, were significantly higher in dermal fibroblasts
      cultured on C-SR coated plates than in dermal fibroblasts cultured on SR. Those
      same dermal fibroblasts on C-SRs showed more pronounced adhesion and migration
      abilities. Osteopontin (OPN), a critical extracellular matrix (ECM) protein, was
      up-regulated and secreted from dermal fibroblasts cultured on C-SR. Matrix
      metalloproteinase-9 (MMP-9) activity was also increased. These cells were highly
      mobile and were able to adhere to surfaces, but these abilities were inhibited by
      the monoclonal antibody against OPN, or by shRNA-mediated MMP-9 knockdown.
      Together, these results suggest that C ion implantation significantly improves SR
      biocompatibility, and that OPN is important to promote cell adhesion to the C-SR
      surface. 

PMID- 24911052
TI  - Association between insulin resistance and breast carcinoma: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: This study was undertaken to evaluate the association between
      components defining insulin resistance and breast cancer in women. STUDY DESIGN:
      We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web
      of Science, and Scopus) for observational studies evaluating components defining
      insulin resistance in women with and without breast cancer. A meta-analysis of
      the association between insulin resistance components and breast cancer was
      performed using random effects models. RESULTS: Twenty-two studies (n = 33,405)
      were selected. Fasting insulin levels were not different between women with and
      without breast cancer (standardized mean difference, SMD -0.03, 95%CI -0.32 to
      0.27; p = 0.9). Similarly, non-fasting/fasting C-peptide levels were not
      different between the two groups (mean difference, MD 0.07, -0.21 to 0.34; p =
      0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no
      higher risk of breast cancer when upper quartiles were compared with the lowest
      quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3
      vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were
      no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs.
      Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03
      to 1.92). Homeostatic model assessment (HOMA-IR) levels in breast cancer patients
      were significantly higher than in people without breast cancer (MD 0.22, 0.13 to
      0.31, p<0.00001). CONCLUSIONS: Higher levels of fasting insulin or non
      fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR
      levels are slightly higher in women with breast cancer.

PMID- 24911055
TI  - Intrinsic relationship between enhanced oxygen reduction reaction activity and
      nanoscale work function of doped carbons.
AB  - Nanostructured carbon materials doped with a variety of heteroatoms have shown
      promising electrocatalytic activity in the oxygen reduction reaction (ORR).
      However, understanding of the working principles that underpin the superior ORR
      activity observed with doped nanocarbons is still limited to predictions based on
      theoretical calculations. Herein, we demonstrate, for the first time, that the
      enhanced ORR activity in doped nanocarbons can be correlated with the variation
      in their nanoscale work function. A series of doped ordered mesoporous carbons
      (OMCs) were prepared using N, S, and O as dopants; the triple-doped, N,S,O-OMC
      displayed superior ORR activity and four-electron selectivity compared to the
      dual-doped (N,O-OMC and S,O-OMC) and the monodoped (O-OMC) OMCs. Significantly,
      the work functions of these heteroatom-doped OMCs, measured by Kelvin probe force
      microscopy, display a strong correlation with the activity and reaction kinetics
      for the ORR. This unprecedented experimental insight can be used to provide an
      explanation for the enhanced ORR activity of heteroatom-doped carbon materials. 

PMID- 24911053
TI  - Observed manipulation enhances left fronto-parietal activations in the processing
      of unfamiliar tools.
AB  - Tools represent a special class of objects, as functional details of tools can
      afford certain actions. In addition, information gained via prior experience with
      tools can be accessed on a semantic level, providing a basis for meaningful
      object interactions. Conceptual representations of tools also encompass knowledge
      about tool manipulation which can be acquired via direct (active manipulation) or
      indirect (observation of others manipulating objects) motor experience. The
      present study aimed to explore the impact of observation of manipulation on the
      neural processing of previously unfamiliar, manipulable objects. Brain activity
      was assessed by means of functional magnetic resonance imaging while participants
      accomplished a visual matching task involving pictures of the novel objects
      before and after they received object-related training. Three training session in
      which subjects observed an experimenter manipulating one set of objects and
      visually explored another set of objects were used to make subjects familiar with
      the tools and to allow the formation of new tool representations. A control
      object set was not part of the training. Training-related brain activation
      increases were found for observed manipulation objects compared to not trained
      objects in a left-hemispheric network consisting of inferior frontal gyrus (iFG)
      pars opercularis and triangularis and supramarginal/angular gyrus. This
      illustrates that direct manipulation experience is not required to elicit tool
      associated activation changes in the action system. While the iFG activation
      might indicate a close relationship between the areas involved in tool
      representation and those involved in observational knowledge acquisition, the
      parietal activation is discussed in terms of non-semantic effects of object
      affordances and hand-tool spatial relationships. 

PMID- 24911056
TI  - Numerical responses of saproxylic beetles to rapid increases in dead wood
      availability following geometrid moth outbreaks in sub-arctic mountain birch
      forest.
AB  - Saproxylic insects play an important part in decomposing dead wood in healthy
      forest ecosystems, but little is known about their role in the aftermath of large
      scale forest mortality caused by pest insect outbreaks. We used window traps to
      study short-term changes in the abundance and community structure of saproxylic
      beetles following extensive mortality of mountain birch in sub-arctic northern
      Norway caused by an outbreak of geometrid moths. Three to five years after the
      outbreak, the proportion of obligate saproxylic individuals in the beetle
      community was roughly 10% higher in forest damaged by the outbreak than in
      undamaged forest. This was mainly due to two early-successional saproxylic beetle
      species. Facultative saproxylic beetles showed no consistent differences between
      damaged and undamaged forest. These findings would suggest a weak numerical
      response of the saproxylic beetle community to the dead wood left by the
      outbreak. We suggest that species-specific preferences for certain wood decay
      stages may limit the number of saproxylic species that respond numerically to an
      outbreak at a particular time, and that increases in responding species may be
      constrained by limitations to the amount of dead wood that can be exploited
      within a given timeframe (i.e. satiation effects). Low diversity of beetle
      species or slow development of larvae in our cold sub-arctic study region may
      also limit numerical responses. Our study suggests that saproxylic beetles, owing
      to weak numerical responses, may so far have played a minor role in decomposing
      the vast quantities of dead wood left by the moth outbreak. 

PMID- 24911054
TI  - Protective effect of the HLA-DRB1*13:02 allele in Japanese rheumatoid arthritis
      patients.
AB  - Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. Certain HLA
      DRB1 "shared-epitope" alleles are reported to be positively associated with
      increased RA susceptibility, whereas some of the other alleles may be negatively
      associated. However, studies on the latter are rare. Here, we focus on the
      protective effects of DRB1 alleles in Japanese RA patients in an association
      study. Relative predispositional effects (RPE) were analyzed by sequential
      elimination of carriers of each allele with the strongest association. The
      protective effects of DRB1 alleles were investigated in patients stratified
      according to whether they possessed anti-citrullinated peptide antibodies (ACPA).
      The DRB1*13:02 allele was found to be negatively associated with RA (P = 4.59*10(
      10), corrected P (Pc) = 1.42*10(-8), odds ratio [OR] 0.42, 95% CI 0.32-0.55, P
      [RPE] = 1.27*10(-6)); the genotypes DRB1*04:05/*13:02 and *09:01/*13:02 were also
      negatively associated with RA. The protective effect of *13:02 was also present
      in ACPA-positive patients (P = 3.95*10(-8), Pc = 1.22*10(-6), OR 0.42, 95%CI 0.31
      0.58) whereas *15:02 was negatively associated only with ACPA-negative RA (P =
      8.87*10(-5), Pc = 0.0026, OR 0.26, 95%CI 0.12-0.56). Thus, this study identified
      a negative association of DRB1*13:02 with Japanese RA; our findings support the
      protective role of DRB1*13:02 in the pathogenesis of ACPA-positive RA.

PMID- 24911057
TI  - Assessment of the potential diagnostic value of serum p53 antibody for cancer: a
      meta-analysis.
AB  - BACKGROUND: Mutant p53 protein over-expression has been reported to induce serum
      antibodies against p53. We assessed the diagnostic precision of serum p53 (s-p53)
      antibodies for diagnosis of cancer patients and compared the positive rates of
      the s-p53 antibody in different types of cancers. METHODS: We systematically
      searched PubMed and Embase, through May 31, 2012. Studies were assessed for
      quality using QUADAS (quality assessment of studies of diagnostic accuracy). The
      positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled
      separately and compared with overall accuracy measures using diagnostic odds
      ratios (DORs) and Area under the curve(AUC). Meta regression and subgroup
      analyses were done, and heterogeneity and publication bias were assessed.
      RESULTS: Of 1089 studies initially identified, 100 eligible studies with 23
      different types of tumor met the inclusion criteria for the meta-analysis (cases
      = 15953, controls = 8694). However, we could conduct independent meta analysis on
      only 13 of 36 types of tumors. Approximately 56% (56/100) of the included studies
      were of high quality (QUADAS score>=8). The summary estimates for quantitative
      analysis of serum p53 antibody in the diagnosis of cancers were: PLR 5.75 (95%
      CI: 4.60-7.19), NLR 0.81 (95%CI: 0.79-0.83) and DOR 7.56 (95% CI: 6.02-9.50).
      However, for the 13 types of cancers on which meta-analysis was conducted, the
      ranges for PLR (2.33-11.05), NLR (0.74-0.97), DOR (2.86-13.80), AUC(0.29-0.81),
      and positive rate (4.47%-28.36%) indicated significant heterogeneity. We found
      that breast, colorectal, esophageal, gastric, hepatic, lymphoma, lung and ovarian
      cancer had relatively reasonable diagnostic accuracy. The remaining results of
      the five types of cancers suggested that s-p53 antibody had limited value.
      CONCLUSIONS: The current evidence suggests that s-p53 antibody has potential
      diagnostic value for cancer, especially for breast, colorectal, esophageal,
      gastric, hepatic, lymphoma, lung and ovarian cancer. The results showed that s
      p53 antibody had high correlation with cancers.

PMID- 24911058
TI  - Lies, damned lies and diagnoses: estimating the clinical utility of assessments
      of covert awareness in the vegetative state.
AB  - BACKGROUND: Functional neuroimaging of patients in the vegetative state has been
      shown to provide diagnostic and prognostic information beyond that which
      conventional behavioural assessments may allow. However, before these promising
      approaches may reach large numbers of patients through a standard clinical
      protocol, it is necessary to determine the utility of these assessments-i.e. the
      accuracy of their diagnoses. METHODS AND RESULTS: This study demonstrated that,
      due to the nature of statistical testing and the absence of a 'ground truth' of
      consciousness, it is impossible to calculate the conventional measures of
      clinical utility-sensitivity and specificity-for diagnoses made on the basis of
      functional neuroimaging for command-following. Nevertheless, it is crucial for
      such measures to be determined in order for valuable clinical resources to be
      distributed wisely. Therefore, a number of alternative guidelines are offered for
      the estimation of clinical utility. CONCLUSIONS: By evaluating new and existing
      functional neuroimaging methods against the proposed guidelines, this study
      argues that it may be possible to achieve dramatically and efficiently improved
      diagnostic and prognostic accuracy for all vegetative state patients.

PMID- 24911059
TI  - Influence of number of benzodioxan-stilbazole-based ancillary ligands on dye
      packing, photovoltage and photocurrent in dye-sensitized solar cells.
AB  - Two novel heteroleptic Ru(II) bipyridyl complexes, HD-2 and HD-2-mono, were
      molecularly engineered, synthesized and characterized for dye-sensitized solar
      cells (DSCs). The influences of mono versus bis electron-donor benzodioxan
      ancillary ligands on optical, dye packing, electrochemical and photovoltaic
      properties were examined and compared to the benchmark N719. HD-2 and HD-2-mono
      achieved solar-to-power conversion efficiencies (%eta) of 9.64 and 9.50,
      respectively, compared to 9.32 for N719 under the same experimental device
      conditions. Optical results showed that HD-2 and HD-2-mono have much higher molar
      extinction coefficients, longer excited state lifetimes and narrower HOMO-LUMO
      gaps compared to N719. Although the molar extinction coefficient of HD-2-mono was
      27% less than that of HD-2, it outperformed HD-2 in photovoltaic performance when
      anchored on TiO2, owing to better dye packing and loading of the former. Charge
      recombination at the dye/TiO2 interface by impedance spectroscopy analysis showed
      that the recombination resistance and the lifetime of injected electron in TiO2
      conduction band is directly proportional to the open-circuit voltage (Voc)
      observed. Furthermore, compared to HD-2 and HD-2-mono, the greater Voc of N719
      can be attributed to the greater negative free energy for dye regeneration. Both
      HD-2 and HD-mono have almost the same negative free energy, which explains why
      they achieved almost the same Voc. Decay dynamic analysis for solar devices
      fabricated from the named dyes, by time correlated single photon counting
      (TCSPC), elucidated that the lowest excited state decay lifetime for HD-2-mono,
      HD-2 and N719 are 3, 10 and 20 ps, respectively. The shorter the decay lifetime,
      the less kinetic redundancy, which leads to better photocurrent, and that
      explanation is consistent with the measured photocurrent and total solar-to-power
      conversion efficiency of the named dyes in the order of HD-2-mono > HD-2 > N719. 

PMID- 24911060
TI  - Maternal food provisioning in a substrate-brooding African cichlid.
AB  - Fish demonstrate the greatest variety of parental care strategies within the
      animal kingdom. Fish parents seldom provision food for offspring, with some
      exceptions predominantly found in substrate-brooding Central American cichlids
      and mouth-brooding African cichlids. Here, we provide the first evidence of food
      provisioning in a substrate-brooding African cichlid Neolamprologus mondabu. This
      fish is a maternal substrate-brooding cichlid endemic to Lake Tanganyika, and
      feeds on benthic animals using unique techniques-individuals typically feed on
      the surface of sandy substrates, but also expose prey by digging up substrates
      with vigorous wriggling of their body and fins. Young also feed on benthos on the
      substrate surface, but only using the first technique. We observed that feeding
      induced by digging accounted for 30% of total feeding bouts in adult females,
      demonstrating that digging is an important foraging tactic. However, parental
      females fed less frequently after digging than non-parental females, although
      both females stayed in pits created by digging for approximately 30 s. Instead,
      young gathered in the pit and fed intensively, suggesting that parental females
      provision food for young by means of digging. We tested this hypothesis by
      comparing the feeding frequency of young before and after digging that was
      simulated by hand, and observed that young doubled their feeding frequency after
      the simulated digging. This suggests that parental females engage in digging to
      uncover food items that are otherwise unavailable to young, and provision food
      for them at the expense of their own foraging. This behavior was similar to what
      has been observed in Central American cichlids. 

PMID- 24911061
TI  - Three dimensional fluorescence imaging using multiple light-sheet microscopy.
AB  - We developed a multiple light-sheet microscopy (MLSM) system capable of 3D
      fluorescence imaging. Employing spatial filter in the excitation arm of a SPIM
      system, we successfully generated multiple light-sheets. This improves upon the
      existing SPIM system and is capable of 3D volume imaging by simultaneously
      illuminating multiple planes in the sample. Theta detection geometry is employed
      for data acquisition from multiple specimen layers. This detection scheme
      inherits many advantages including, background reduction, cross-talk free
      fluorescence detection and high-resolution at long working distance. Using this
      technique, we generated 5 equi-intense light-sheets of thickness approximately
      7.5 MUm with an inter-sheet separation of 15 MUm. Moreover, the light-sheets
      generated by MLSM is found to be 2 times thinner than the state-of-art SPIM
      system. Imaging of fluorescently coated yeast cells of size 4 +/- 1 MUm (encaged
      in Agarose gel-matrix) is achieved. Proposed imaging technique may accelerate the
      field of fluorescence microscopy, cell biology and biophotonics.

PMID- 24911062
TI  - Particulate matter air pollution exposure, distance to road, and incident lung
      cancer in the nurses' health study cohort.
AB  - BACKGROUND: A body of literature has suggested an elevated risk of lung cancer
      associated with particulate matter and traffic-related pollutants. OBJECTIVE: We
      examined the relation of lung cancer incidence with long-term residential
      exposures to ambient particulate matter and residential distance to roadway, as a
      proxy for traffic-related exposures. METHODS: For participants in the Nurses'
      Health Study, a nationwide prospective cohort of women, we estimated 72-month
      average exposures to PM2.5, PM2.5-10, and PM10 and residential distance to road.
      Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox
      proportional hazards models were adjusted for potential confounders. Effect
      modification by smoking status was examined. RESULTS: During 1,510,027 person
      years, 2,155 incident cases of lung cancer were observed among 103,650
      participants. In fully adjusted models, a 10-MUg/m3 increase in 72-month average
      PM10 [hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14], PM2.5 (HR = 1.06; 95% CI:
      0.91, 1.25), or PM2.5-10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively
      associated with lung cancer. When the cohort was restricted to never-smokers and
      to former smokers who had quit at least 10 years before, the associations
      appeared to increase and were strongest for PM2.5 (PM10: HR = 1.15; 95% CI: 1.00,
      1.32; PM2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM2.5-10: HR = 1.11; 95% CI: 0.90,
      1.37). RESULTS were most elevated when restricted to the most prevalent subtype,
      adenocarcinomas. Risks with roadway proximity were less consistent. CONCLUSIONS:
      Our findings support those from other studies indicating increased risk of
      incident lung cancer associated with ambient PM exposures, especially among never
      and long-term former smokers.

PMID- 24911065
TI  - Urotropine isomer (1,4,6,10-tetraazaadamantane): synthesis, structure, and
      chemistry.
AB  - The first synthesis of 1,4,6,10-tetraazaadamantane, the C3v-symmetrical
      structural isomer of urotropine (1,3,5,7-tetraazaadamantane), and a series of its
      derivatives is reported. X-ray and quantum-chemical studies revealed remarkable
      distinctions in structures of urotropine and "isourotropine" cations, probably
      arising from different types of hyperconjugation between lone electron pairs of
      nitrogen atoms and sigma*C-N orbitals in these heterocage systems. Since
      substitution at bridge and bridgehead nitrogen atoms can be easily introduced,
      1,4,6,10-tetraazaadamantane may be considered as a new rigid multivalent (3 + 1)
      scaffold for the design of functional molecules and materials. 

PMID- 24911064
TI  - Association of FTO polymorphisms with obesity and metabolic parameters in Han
      Chinese adolescents.
AB  - BACKGROUND: Previous studies have suggested that fat mass-and obesity-associated
      (FTO) gene is associated with body mass index (BMI) and the risk of obesity. This
      study aims to assess the association of five FTO polymorphisms (rs9939609,
      rs8050136, rs1558902, rs3751812 and rs6499640) with obesity and relative
      parameters in Han Chinese adolescents. METHODS: We examined a total of 401
      adolescents, 223 normal weights (58.7% boys, 41.3% girls), 178 overweight (60.1%
      boys, 39.9% girls), aging from 14 to 18-years-old, recruited randomly from public
      schools in the central region of Wuxi, a southern city of China. DNA samples were
      genotyped for the five polymorphisms by Sequenom Plex MassARRAY. Association of
      the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting
      insulin (FIns), triglyceride (TG) and cholesterol (TC) were investigated.
      RESULTS: 1) Serum FPG, FIns, TG and TC were statistically significant higher than
      that in normal control group. 2) We found that BMI was higher in the rs9939609
      TA+AA, rs8050136 AC+AA, rs1558902 TA+AA and rs3751812 GT+TT genotypes than in
      wild TT genotypes (rs9939609: P = 0.038; rs1558902: P = 0.038;), CC
      genotypes(rs8050136: P = 0.024) and GG genotypes (rs3751812: P = 0.024), which
      were not significant on adjusting for multiple testing. 3) In case-control
      studies, five polymorphisms were not significantly associated with overweight
      (p>0.05), haplotype analyses showed non-haplotype is significantly associated
      with a higher risk of being overweight (p>0.05). 4) There existed no significant
      statistical difference about FPG, FIns, TG and TC in genotype model for any SNP.
      CONCLUSIONS: Our study has conducted a genetic association study of the FTO
      polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin
      (FIns), triglyceride (TG) and cholesterol (TC). Our study found BMI of subjects
      with A allele of FTO rs9939609 is higher than that with T allele. Further studies
      on other polymorphisms from FTO and increasing the sample size are needed.

PMID- 24911063
TI  - A novel strategy for enrichment and isolation of osteoprogenitor cells from
      induced pluripotent stem cells based on surface marker combination.
AB  - In this study, we developed a new method to stimulate osteogenic differentiation
      in tissue-nonspecific alkaline phosphatase (TNAP)-positive cells liberated from
      human induced pluripotent stem cells (hiPSCs)-derived embryoid bodies (EBs) with
      14 days long TGF-beta/IGF-1/FGF-2 treatment. TNAP is a marker protein of
      osteolineage cells. We analyzed and isolated TNAP-positive and E-cadherin
      negative nonepithelial cells by fluorescence-activated cell sorting. Treating the
      cells with a combination of transforming growth factor (TGF)-beta, insulin-like
      growth factor (IGF)-1, and fibroblast growth factor (FGF)-2 for 14 days greatly
      enhanced TNAP expression and maximized expression frequency up to 77.3%. The
      isolated cells expressed high levels of osterix, which is an exclusive osteogenic
      marker. Culturing these TNAP-positive cells in osteoblast differentiation medium
      (OBM) led to the expression of runt-related transcription factor 2, type I
      collagen, bone sialoprotein, and osteocalcin (OCN). These cells responded to
      treatment with activated vitamin D3 by upregulating OCN. Furthermore, in OBM they
      were capable of generating many mineralized nodules with strong expression of
      receptor activator of NF-kappaB ligand and sclerostin (SOST). Real-time RT-PCR
      showed a significant increase in the expression of osteocyte marker genes,
      including SOST, neuropeptide Y, and reelin. Scanning electron microscopy showed
      dendritic morphology. Examination of semi-thin toluidine blue-stained sections
      showed many interconnected dendrites. Thus, TNAP-positive cells cultured in OBM
      may eventually become terminally differentiated osteocyte-like cells. In
      conclusion, treating hiPSCs-derived cells with a combination of TGF-beta, IGF-1,
      and FGF-2 generated TNAP-positive cells at high frequency. These TNAP-positive
      cells had a high osteogenic potential and could terminally differentiate into
      osteocyte-like cells. The method described here may reveal new pathways of
      osteogenesis and provide a novel tool for regenerative medicine and drug
      development. 

PMID- 24911066
TI  - Newborn boys and girls differ in the lipid composition of vernix caseosa.
AB  - Vernix caseosa protects the skin of a human fetus during the last trimester of
      pregnancy and of a newborn after the delivery. Besides its cellular and
      proteinaceous components, an important constituent and functional agent is a
      complex lipid fraction, implicated in a multitude of salubrious effects of vernix
      caseosa. Little is known about how the chemical composition of vernix caseosa
      lipids is affected by various biological characteristics of the baby, such as the
      gestational age, birth weight, and, last but not least, the gender of the
      newborn. This study reports on the chemical variability of lipids contained in
      the vernix caseosa of twenty newborn girls and boys and shows that the
      quantitative patterns of the lipids are sex-specific. The specificity of lipids
      was investigated at the level of fatty acids in the total lipid extracts and
      intact lipids of several neutral lipid classes. Hydrocarbons, wax esters,
      cholesteryl esters, diol diesters and triacylglycerols were isolated using
      optimized semipreparative thin-layer chromatography, and the molecular species
      within each class were characterized using matrix-assisted laser
      desorption/ionization mass spectrometry. Statistical evaluation revealed
      significant quantitative sex-related differences in the lipid composition of
      vernix caseosa among the newborns, pronounced in the two lipid classes associated
      with the activity of sebaceous glands. Higher proportions of wax esters and
      triacylglycerols with longer hydrocarbon chains were observed in newborn girls. 

PMID- 24911068
TI  - Clinical approaches to treatment of Internet addiction.
AB  - BACKGROUND: Internet appearance was one of the main breakthroughs for the mankind
      in the latest decades. It revolutionized our lives in many aspects and brought
      about many undeniably positive changes. However, at the same time caused negative
      consequences. It has led to the emergence of the Internet addiction (IA). The
      paper is concerned with the issue of treatment of IA. METHOD: The paper reviews
      the current findings on the approaches to IA treatment and evaluates their
      effectiveness. The main focus of the article concentrates on cognitive and
      pharmacologic treatment. RESULTS: The individual approach to IA treatment is
      advisable. Among drugs for the management of IA, antidepressants, antipsychotics,
      opioid receptor antagonists, glutamate receptor antagonists, and psychostimulants
      may be recommended. Some antiepileptics, and especially valproate, are considered
      as potential drugs for the treatment of IA. CONCLUSION: Effective therapy may
      require an individual approach and best results are expected when psychological
      and pharmacological treatments are combined.

PMID- 24911067
TI  - Resident intruder paradigm-induced aggression relieves depressive-like behaviors
      in male rats subjected to chronic mild stress.
AB  - BACKGROUND: Accumulating epidemiological evidence shows that life event stressors
      are major vulnerability factors for psychiatric diseases such as major
      depression. It is also well known that the resident intruder paradigm (RIP)
      results in aggressive behavior in male rats. However, it is not known how
      resident intruder paradigm-induced aggression affects depressive-like behavior in
      isolated male rats subjected to chronic mild stress (CMS), which is an animal
      model of depression. MATERIAL AND METHODS: Male Wistar rats were divided into 3
      groups: non-stressed controls, isolated rats subjected to the CMS protocol, and
      resident intruder paradigm-exposed rats subjected to the CMS protocol. RESULTS:
      In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS
      group was significantly lower than in control and CMS+RIP rats after 3 weeks of
      stress. In the open-field test, CMS rats had significantly lower open-field
      scores compared to control rats. Furthermore, the total scores given the CMS
      group were significantly lower than in the CMS+RIP rats. In the forced swimming
      test (FST), the immobility times of CMS rats were significantly longer than those
      of the control or CMS+RIP rats. However, no differences were observed between
      controls and CMS+RIP rats. CONCLUSIONS: Our data show that aggressive behavior
      evoked by the resident intruder paradigm could relieve broad-spectrum depressive
      like behaviors in isolated adult male rats subjected to CMS.

PMID- 24911069
TI  - Skin-induced tolerance as a new needle free therapeutic strategy.
AB  - This article summarizes current knowledge about a new subject called "skin
      induced tolerance". Suppression is induced via epicutaneous (EC) immunization
      with a protein antigen and is described in Th1, Tc1 and NK mediated contact
      hypersensitivity (CHS) reactions. The subject of skin-induced suppression is also
      described in the regulation of experimental models of autoimmune diseases like
      experimental autoimmune encephalomyelitis (EAE), collagen induced arthritis (CIA)
      and inflammatory bowel disease (IBD) and finally in an animal model of graft
      rejection. The potential clinical use of this approach to regulate human diseases
      is also discussed. 

PMID- 24911070
TI  - Cocaine-induced glutamate receptor trafficking is abrogated by extinction
      training in the rat hippocampus.
AB  - BACKGROUND: It has been demonstrated that long-term exposure to cocaine leads to
      plastic changes in the brain that contribute to the manifestation of addictive
      behaviors. While attention has mostly focused on the meso-cortico-limbic pathway,
      the hippocampus seems to play a role in the craving induced by cues in drug
      addicts, in particular in cue- and drug-induced reinstatement of cocaine seeking.
      Since glutamate appears to be critical for context-induced drug seeking
      behaviors, the major aim of our work was to investigate the expression of
      hippocampal AMPA and NMDA glutamate receptors following repeated cocaine exposure
      and during extinction training. METHODS: We thus employed the yoked control
      operant paradigm and exposed the animals to contingent or non-contingent cocaine
      exposure for 2 weeks and sacrificed the animals after the last self
      administration (SA) session and following 1 or 10 days of extinction. Protein
      levels of glutamate receptors were analyzed by Western blotting. RESULTS: We
      found increased levels of the main subunits of both NMDA and AMPA receptors in
      the post-synaptic density (PSD) fraction, but not in the whole homogenate, of the
      hippocampus of animals repeatedly exposed to cocaine indicating increased
      trafficking toward the membrane of these receptors. Also, we found that
      extinction abolished such effect, suggesting that the trafficking was tightly
      linked to the presence of the psychostimulant. CONCLUSIONS: These data reveal a
      novel, previously unappreciated role of glutamate receptors in the action of
      cocaine and cocaine-extinction behavior in rat hippocampus.

PMID- 24911072
TI  - Influence of calcium channel antagonists on nonsomatic signs of nicotine and D
      amphetamine withdrawal in mice.
AB  - BACKGROUND: Nonsomatic signs of psychostimulant withdrawal, difficult to
      demonstrate in animal paradigms, may appear to promote drug seeking and drug
      relapse in humans; thus, it is important to understand the mechanisms that
      mediate this kind of behaviors. The present study was undertaken to examine the
      calcium-dependent mechanism of negative nonsomatic and anhedonia-related symptoms
      of acute and protracted withdrawal of nicotine and D-amphetamine. METHODS: Mice
      were chronically treated with nicotine (seven days, three times daily, 3.35
      mg/kg, sc) or D-amphetamine (14 days, once daily, 2.5mg/kg, ip). Then, at the
      first, seventh or 14th day of withdrawal, anxiety- or depression-related effects,
      as well as cognition or nociception were studied. RESULTS: Our results
      demonstrated that, at the seventh or 14th day of D-amphetamine or nicotine
      withdrawal, respectively, mice exhibited increased anxiety and depression-like
      effects, memory impairment and hyperalgesia. Further, major findings showed that
      calcium channel antagonists, i.e., nimodipine, verapamil and flunarizine (10 and
      20mg/kg, ip), injected before the test, attenuated above-mentioned signs of drug
      withdrawal. CONCLUSIONS: As an outcome, these findings support the hypothesis
      that similar calcium-dependent mechanisms are involved in an aversive nonsomatic
      component, associated with nicotine or d-amphetamine withdrawal. We can suggest
      that calcium channel blockers have potential to alleviate drug withdrawal and may
      thus be beneficial as pharmacotherapy of drug cessation and relapse.

PMID- 24911071
TI  - Inhibitory actions of mGlu4 receptor ligands on cocaine-, but not nicotine-,
      induced sensitizing and conditioning locomotor responses in rats.
AB  - BACKGROUND: Male Wistar rats were used to verify the hypothesis that metabotropic
      glutamate 4 (mGlu4) receptor ligands may modulate the locomotor effects evoked by
      cocaine or nicotine. METHODS: The preferential mGlu4 receptor orthosteric agonist
      (2S)-2-amino-4-[hydroxy[hydroxy(4-hydroxy-3-methoxy-5
      nitrophenyl)methyl]phosphoryl]butanoic acid (LSP1-2111) and the mGlu4 receptor
      positive allosteric modulator (+)-cis-N(1)-(3,4-dichlorophenyl)cyclohexane-1,2
      dicarboxamide (Lu AF21934) were used in the study. Rats were given repeated
      pairings of a test environment with cocaine (10mg/kg), nicotine (0.4 mg/kg) or
      the respective vehicles for 5 days. On day 10, animals were challenged with
      cocaine (10mg/kg, cocaine sensitization), nicotine (0.4 mg/kg, nicotine
      sensitization) or vehicle (conditioned hyperlocomotion) in experimental cages.
      RESULTS: Given on day 10, LSP1-2111 (3mg/kg) as well as Lu AF21934 (2.5-5mg/kg)
      decreased the expression of cocaine sensitization. In another set of experiments,
      LSP1-2111 (3mg/kg) and Lu AF21934 (5mg/kg) administered on day 10 attenuated the
      conditioned hyperlocomotion in rats treated repeatedly with cocaine. Neither LSP1
      2111 (1-3mg/kg) nor Lu AF21934 (2.5-5mg/kg) changed the expression of nicotine
      sensitization and conditioned hyperlocomotion in rats treated repeatedly with
      nicotine. None of the mGlu4 receptor agonist/modulator altered the basal
      locomotor activity or acute hyperactivity to cocaine or nicotine. CONCLUSIONS:
      The present data indicate that pharmacological stimulation of mGlu4 receptors
      reduces the cocaine-induced expression of sensitization as well as conditioned
      hyperactivity. In contrast, mGlu4 receptor activation seems to be devoid of any
      effect on the locomotor effects of nicotine.

PMID- 24911073
TI  - An anti-immobility effect of spermine in the forced swim test in mice.
AB  - BACKGROUND: Spermine is one of the naturally occurring ligands that influence the
      function of the N-methyl-D-aspartate receptor. Similar to other endogenous
      polyamines present in micromolar concentration in the brain, it may play a role
      in the modulation of depression. Thus, the present study investigated the
      suggested antidepressant effect of spermine. METHODS: The mouse forced swim test
      (FST) was used as a reliable tool that allowed us to determine the antidepressant
      activity. RESULTS: Spermine, administered intracerebroventricularly (icv),
      significantly and dose-dependently reduced the immobility time in the FST within
      the dose range of 5-20 MUg without changing the spontaneous locomotor activity.
      The pre-treatment of the animals with ifenprodil (an antagonist of the polyamine
      binding site of the NMDA receptor), given intraperitoneally at a dose of 20mg/kg,
      thoroughly reversed the anti-immobility effect of spermine (5 MUg, icv).
      CONCLUSION: Our preliminary study revealed the anti-immobility activity of
      centrally administered spermine in the FST in mice, with a probable involvement
      of the polyamine-binding site at the NMDA receptor complex.

PMID- 24911074
TI  - Enhancement of antinociceptive effect of morphine by antidepressants in diabetic
      neuropathic pain model.
AB  - BACKGROUND: Recent studies have shown that influence of antidepressants on
      analgesic action of opioids is heterogeneous. The aim of this study was to
      investigate the effect of acute and repeated (21 days) antidepressant
      (amitriptyline, moclobemide and reboxetine) treatment on the antinociceptive
      action of morphine, an opioid agonist, in streptozotocin (STZ)-induced
      neuropathic pain model. METHODS: The studies were performed on the male Wistar
      rats. The changes in nociceptive thresholds were determined by using mechanical
      stimuli (the Randall-Selitto and the von Frey tests). Diabetes was induced by
      intramuscular administration of STZ. RESULTS: In this work we report that acute
      as well as repeated per os administration of antidepressants (amitriptyline,
      moclobemide and reboxetine) significantly potentiated the antihyperalgesic effect
      of morphine in STZ-induced neuropathic pain model. CONCLUSION: Combination
      therapy, such as classical antidepressants (amitriptyline, moclobemide) with
      opioids, or agents with noradrenaline reuptake inhibition and MU-opioid receptor
      activation could be a new target for research into treatment of painful diabetic
      neuropathy.

PMID- 24911076
TI  - A clinical comparison of the efficacy and safety of biosimilar G-CSF and
      originator G-CSF in haematopoietic stem cell mobilization.
AB  - BACKGROUND: Recombinant granulocyte colony-stimulating factor (G-CSF) is widely
      used to mobilize haematopoietic stem cells. We compared the efficacy and safety
      of a biosimilar G-CSF (Zarzio((r)), Sandoz Biopharmaceuticals) with the
      originator G-CSF (Neupogen((r)), Amgen) in patients with haematological
      malignancies. METHODS: A total of 108 patients were included in this study, 59 of
      whom were female (49 male), with an overall median age of 51 years (range 19-69).
      Patients had multiple myeloma (n=46), non-Hodgkin's lymphoma (n=28), Hodgkin's
      lymphoma (n=26), or other diagnosis (n=8). After administration of mobilizing
      regimens (primarily high-dose etoposide, high-dose cyclophosphamide, intermediate
      dose Ara-C or ESHAP), patients were randomized to a standard daily 10 MUg/kg dose
      of biosimilar G-CSF (n=54) or originator G-CSF (n=54). RESULTS: Median duration
      of G-CSF administration was 8 days with both biosimilar G-CSF (range 4-17) and
      originator G-CSF (range 4-14). Both groups had a median of one apheresis with a
      median time until first apheresis of 11 days. There were no statistically
      significant differences between groups in the mean +/- SD number of mobilized
      CD34+ cells/MUL in peripheral blood or the number of CD34+ cells/kg body weight.
      Five patients (9%) in the originator G-CSF group and six patients in the
      biosimilar G-CSF group (11%) did not mobilize sufficient CD34+ cells. The adverse
      event profile was similar between groups. CONCLUSIONS: A biosimilar G-CSF
      (Zarzio((r))) demonstrated similar efficacy and safety as the reference
      originator G-CSF (Neupogen((r))) in hematopoietic stem cell mobilization in
      patients with haematological malignancies.

PMID- 24911075
TI  - ABCB1 C3435T polymorphism is associated with susceptibility to major depression,
      but not with a clinical response to citalopram in a Turkish population.
AB  - BACKGROUND: The ATP-binding cassette sub-family B member 1 (ABCB1) gene, which
      encodes the p-glycoprotein at the blood-brain barrier, is investigated for
      patients' susceptibility to major depressive disorder (MDD) and their therapeutic
      response to antidepressants. However, there is an inconsistency between the
      studies of different ethnic groups. The current study aimed to determine the
      potential correlations of the ABCB1 gene C3435T polymorphism with the
      susceptibility to MDD and the therapeutic response to citalopram in a Turkish
      population. METHODS: Fifty-four patients with MDD who received citalopram and 70
      controls from the Turkish population were genotyped for ABCB1 C3435T
      polymorphism. To assess the therapeutic response to citalopram, all patients were
      rated baseline, first, second, fourth and sixth weeks according to the 17-item
      Hamilton Rating Scale for Depression (HAMD-17). RESULTS: There was a significant
      correlation between the patient and control groups for ABCB1 C3435T polymorphism.
      Distribution of CC genotype and C allele frequency were higher in the patients
      than in the control group (p = 0.006, p = 0.020, respectively). However, no
      correlation between ABCB1 C3435T polymorphism and a therapeutic response to
      citalopram was observed. CONCLUSION: Our results suggested that C3435T
      polymorphism in the ABCB1 gene may be an indicator of the susceptibility to major
      depression, without a likely treatment response to citalopram in a Turkish
      population. These findings should be replicated in studies on larger patient
      groups with different ethnicities.

PMID- 24911077
TI  - CYP2C9, VKORC1, CYP4F2, ABCB1 and F5 variants: influence on quality of long-term
      anticoagulation.
AB  - AIMS: The study aims to evaluate the impact of genetic, demographic and clinical
      data on various measures of outcome of anticoagulation quality in patients.
      PATIENTS AND METHODS: The study consisted of 310 patients receiving long-term
      oral anticoagulation therapy in our hospital. Apart from demographic and clinical
      variables, 21 SNPs (in 7 genes) were analyzed and compared with the outcomes of
      anticoagulation therapy. Various outcomes that were measured are; supra
      therapeutic INRs (INR >3, >6), anticoagulation stabilization, time taken to
      stabilize and proportion of INRs within (2-3), above (>3) and below (<2)
      therapeutic range. RESULTS: Supra therapeutic INRs were influenced by CYP2C9*2,
      *3, CYP4F2 rs2108622, VKORC1-1639G>A, 1173C>T, rs55894764 along with concomitant
      drugs, smoking, body weight and height. Persistently fluctuating INRs/absolute
      instability correlated with VKORC1-1639G>A, gender, height and body mass index.
      The time taken to stabilize was associated with CYP4F2 rs2108622, CYP2C9*14,
      smoking, clinical indication and concomitant drugs. The overall distribution of
      INR was influenced by variants in CYP4F2 rs2108622, CYP2C9*3, rs9332230, VKORC1
      1173C>T, -1639G>A, rs55894764, ABCB1 rs2032582, rs1128503, rs1045642 and F5
      rs6025, age, smoking and concomitant drugs. CONCLUSIONS: Knowledge of factors
      influencing the quality of long term anticoagulation can help clinicians to
      customize therapy either by dose variation, therapy with alternate choice of
      drug, concurrent heparin therapy and/or frequent INR monitoring.

PMID- 24911078
TI  - Partial depletion of natural gut flora by antibiotic aggravates collagen induced
      arthritis (CIA) in mice.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that
      affects about 1% of the adult population and occurs twice as frequently among
      women than men. At present it is accepted that pathogenesis of RA is based on
      inflammatory response mediated by CD4(+) Th1 and Th17 lymphocytes. The most
      commonly applied model imitating RA is the collagen induced arthritis (CIA). A
      growing evidence shows that there is a correlation between microbial dysbiosis
      and human pathology which includes autoimmunity, allergic diseases, obesity,
      inflammatory bowel disease (IBD), metabolic syndrome. METHODS: Collagen induced
      arthritis was used to study influence of natural gut flora on course of
      rheumatoid arthritis. RESULTS: Current work employing CIA model showed that
      partial depletion of natural gut flora with orally administered antibiotic
      Baytril (enrofloxacin) aggravates disease severity when compared to control mice.
      Observed partial depletion of both aerobic and anaerobic bacteria did not affect
      animal body weight. Additionally, in vitro study showed increased production of
      IFN-? and IL-17A and decreased release of IL-4 by axillary lymph node cells
      (ALNC) isolated from mice treated with antibiotic and induced CIA when compared
      to positive control. Furthermore, treatment with antibiotic prior to CIA
      induction results in augmented production of IFN-?, IL-17A and IL-6 by mesenteric
      lymph node cells (MLNC). CONCLUSION: Presented data suggest that alteration of
      gut microbiota via use of enrofloxacin may play a role in modulating arthritis
      symptom severity in this mouse model.

PMID- 24911079
TI  - The endocannabinoid anandamide regulates the peristaltic reflex by reducing neuro
      neuronal and neuro-muscular neurotransmission in ascending myenteric reflex
      pathways in rats.
AB  - BACKGROUND: Endocannabinoids (EC) and the cannabinoid-1 (CB1) receptor are
      involved in the regulation of motility in the gastrointestinal (GI) tract.
      However, the underlying physiological mechanisms are not completely resolved. The
      purpose of this work was to study the physiological influence of the
      endocannabinoid anandamide, the putative endogenous CB1 active cannabinoid, and
      of the CB1 receptor on ascending peristaltic activity and to identify the
      involved neuro-neuronal, neuro-muscular and electrophysiological mechanisms.
      METHODS: The effects of anandamide and the CB1 receptor antagonist SR141716A were
      investigated on contractions of the circular smooth muscle of rat ileum and in
      longitudinal rat ileum segments where the ascending myenteric part of the
      peristaltic reflex was studied in a newly designed organ bath. Additionally
      intracellular recordings were performed in ileum and colon. RESULTS: Anandamide
      significantly reduced cholinergic twitch contractions of ileum smooth muscle
      whereas SR141716A caused an increase. Anandamide reduced the ascending
      peristaltic contraction by affecting neuro-neuronal and neuro-muscular
      neurotransmission. SR141716A showed opposite effects and all anandamide effects
      were antagonized by SR141716A (1 MUM). Anandamide reduced excitatory junction
      potentials (EJP) and inhibitory junction potentials (IJP), whereas intestinal
      slow waves were not affected. CONCLUSIONS: CB1 receptors regulate force and
      timing of the intestinal peristaltic reflex and these actions involve
      interneurons and motor-neurons. The endogenous cannabinoid anandamide mediates
      these effects by activation of CB1 receptors. The endogenous cannabinoid system
      is permanently active, suggesting the CB1 receptor being a possible target for
      the treatment of motility related disorders.

PMID- 24911080
TI  - Beneficial role of tamoxifen in experimentally induced cardiac hypertrophy.
AB  - BACKGROUND: Protein kinase C (PKC) activation is associated with cardiac
      hypertrophy (CH), fibrosis, inflammation and cardiac dysfunction. Tamoxifen is a
      PKC inhibitor. Despite these, reports on effect of tamoxifen on cardiac
      hypertrophy are not available. Hence, we have investigated effect of tamoxifen
      (2mg/kg/day, po) on CH. METHODS: In isoproterenol (ISO) induced CH, ISO
      (5mg/kg/day, ip) was administered for 10 days in Wistar rats. For partial
      abdominal aortic constriction (PAAC), abdominal aorta was ligated by 4-0 silk
      thread around 7.0mm diameter blunt needle. Then the needle was removed to leave
      the aorta partially constricted for 30 days. Tamoxifen was given for 10 days and
      30 days, respectively, in ISO and PAAC models and at end of each studies, animals
      were sacrificed and biochemical and cardiac parameters were evaluated. RESULTS:
      ISO and PAAC produced significant dyslipidemia, hypertension, bradycardia,
      oxidative stress and increase in serum lactate dehydrogenase and creatine kinase
      MB, C-reactive protein. Treatment with tamoxifen significantly controlled
      dyslipidemia, hypertension, bradycardia, oxidative stress and reduced serum
      cardiac markers. ISO control and PAAC control rats exhibited significantly
      increased cardiac and left ventricular (LV) hypertrophic index, LV thickness,
      cardiomyocyte diameter. Treatment with tamoxifen significantly reduced these
      hypertrophic indices. There was a significant increase in LV collagen level,
      decrease in Na(+)K(+)ATPase activity, and reduction in the rate of pressure
      development and decay. Tamoxifen significantly reduced LV collagen, increased
      Na(+)K(+)ATPase activity and improved hemodynamic function. This was further
      supported by histopathological studies, in which tamoxifen showed marked decrease
      in fibrosis and increase in extracellular spaces in the treated animals.
      CONCLUSIONS: Our data suggest that tamoxifen produces beneficial effects on
      cardiac hypertrophy and hence may be considered as a preventive measure for
      cardiac hypertrophy.

PMID- 24911081
TI  - Effects of liposomes with polyisoprenoids, potential drug carriers, on the
      cardiovascular and excretory system in rats.
AB  - BACKGROUND: The unpredictable side effects of a majority currently used drugs are
      the substantial issue, in which patients and physicians are forced to deal with.
      Augmenting the therapeutic efficacy of drugs may prove more fruitful than
      searching for the new ones. Since recent studies show that new cationic
      derivatives of polyisoprenoid alcohols (APrens) might exhibit augmenting
      properties, we intend to use them as a component of liposomal drug carriers. In
      this study we investigate if these compounds do not per se cause untoward effects
      on the living organism. METHODS: Male Sprague-Dawley rats received for four weeks
      daily injections (0.5 ml sc) of liposomes built of dioleoyl
      phosphatidylethanolamine (DOPE), liposomes built of DOPE and APren-7 (ratio 10:1)
      or water solvent. Weekly, rats were observed in metabolic cages (24h); blood and
      urine were sampled for analysis; body weight (BW) and systolic blood pressure
      (SBP) were determined. After chronic experiment, kidneys and heart were harvested
      for histological and morphometric analysis. RESULTS: The 4-week BW increments
      were in the range of 97 +/- 4 to 102 +/- 4%, intergroup differences were not
      significant. Microalbuminuria was the lowest in the group receiving liposomes
      with APren-7 (0.22 +/- 0.03 mg/day). Water and food intake, plasma and urine
      parameters were similar in all groups. CONCLUSIONS: Newly designed liposomes
      containing APren-7 did not affect functions of the excretory and cardiovascular
      systems, and renal morphology; therefore we find them suitable as a component of
      liposomal drug carriers.

PMID- 24911082
TI  - The comparative effects of perindopril and catechin on mesangial matrix and
      podocytes in the streptozotocin induced diabetic rats.
AB  - BACKGROUND: Hyperglycemia and advanced glucose end substance (AGE) are
      responsible for excessive reactive oxygen species (ROS) production, which causes
      oxidative stress in diabetes mellitus. Oxidative stress and high blood pressure
      may cause injury and glomerulosclerosis in the kidney. End-stage kidney failure
      induced by glomerulosclerosis leads to microalbuminuria (Ma) in diabetic
      nephropathy. We investigated the effects of an angiotensin converting enzyme
      inhibitor (ACEI), perindopril, and an antioxidant, catechin, on podocytes and the
      glomerular mesangial matrix in experimental diabetic nephropathy using
      ultrastructural visualization and immunohistochemical staining. METHODS: We
      compared 5 groups of male adult Wistar albino rats: a control group, an untreated
      diabetic group, and diabetic groups treated with perindopril, catechin, or
      catechin+perindopril. RESULTS: Blood glucose values in all diabetic groups were
      significantly higher than in the control group (p < 0.001). The body weight in
      all diabetic groups was significantly lower than in the control group (p < 0.001,
      p < 0.05). The kidney weight in the catechin+perindopril-treated diabetic group
      was significantly lower than in the untreated diabetic group (p < 0.001). In all
      treated diabetic groups, Ma levels decreased significantly (p < 0.001). Mesangial
      matrix and podocyte damage increased in the untreated diabetic group, but the
      group treated with catechin+perindopril showed less damage. TGF-beta 1
      immunostaining was significantly lower in the catechin-treated and perindopril
      treated groups than in the untreated diabetic group (p < 0.001). Catechin was
      more effective than ACEI in preventing podocyte structure. Podocytes appeared to
      be the first cells affected in diabetes mellitus. When exposed to hyperglycemia,
      podocytes caused the mesangial matrix to expand. CONCLUSIONS: Catechin and
      perindopril were more effective in preventing renal corpuscle damage when
      administered together.

PMID- 24911083
TI  - Interactions of orphanin FQ/nociceptin (OFQ/N) system with immune system factors
      and hypothalamic-pituitary-adrenal (HPA) axis.
AB  - BACKGROUND: Brain-immune system interactions and neurohormonal changes which are
      induced by psychophysiological factors are growing areas of scientific interest.
      Central (CNS) and autonomic nervous-endocrine-immune system pathways are
      connected with a number of behavioral and physiological factors which may be
      linked to disease susceptibility and progression. METHODS: In this paper,
      influence of orphanin FQ/nociceptin receptor (OFQ/N) on the hypothalamic
      pituitary-adrenal (HPA) axis and their influence on the immunological system was
      reviewed. CONCLUSIONS: The neuroendocrine system, in particular the hypothalamic
      pituitary-adrenal (HPA) axis, is closely connected with the cytokines. HPA axis
      activation by cytokines, via the release of glucocorticoids has, in turn, been
      found to play a critical role in restraining and shaping immune responses.
      Investigation of the OFQ/N system and G-proteins suggests a role for this
      receptor as a down-regulator of cytokine, chemokine and chemokine receptor
      expression.

PMID- 24911084
TI  - The effect of quercetin and imperatorin on programmed cell death induction in
      T98G cells in vitro.
AB  - BACKGROUND: High expression of HSP27 and HSP72 in glioma cells has been closely
      associated with chemoresistance and decreased sensitivity to programmed cell
      death induction. Therefore, it is important to devise therapies that effectively
      target invasive cancer cells by inducing cell death. The aim of our study was to
      assess the effect of quercetin and imperatorin applied separately and in
      combinations on the apoptosis and autophagy induction in human T98G cells
      cultured in vitro. METHODS: Cell death induction was analyzed by the staining
      method. The Western blotting technique and fluorimetric measurements of activity
      were used to assess the expression of marker proteins of apoptosis and autophagy.
      The specific siRNA transfected method was used for blocking of the expression of
      HSP27 and HSP72 genes. RESULTS: The experiments revealed the highest percentage
      of apoptotic cells after using a 50?M concentration of both compounds.
      Simultaneous quercetin and imperatorin administration induced apoptosis more
      effectively than incubation with single drugs. These results were accompanied
      with decreased HSP27 and HSP72 expression, and a high level of caspase-3 and
      caspase-9 activity. Autophagy was not observed. Additional experiments were
      performed on a cell line with blocked Hsp27 and Hsp72 expression and significant
      increase the sensitivity to apoptosis induction upon quercetin and imperatorin
      treatment was noticed. CONCLUSIONS: The present study indicates that quercetin
      and imperatorin are potent apoptosis inducers, especially when they act
      synergistically, which may be a promising combination useful in glioma therapy.
      Our results also demonstrated that blocking the HSP27 and HSP72 gene expression
      might serve as a therapeutic target for the human brain cancer.

PMID- 24911085
TI  - Effects of Selol 5% supplementation on the activity or concentration of
      antioxidants and malondialdehyde level in the blood of healthy mice.
AB  - BACKGROUND: Selol is a novel organoselenium Se(IV) compound. It reveals lower
      potential of toxicity than sodium selenite and does not exhibit mutagenic
      activity. Its antioxidant and anticancer properties including overcoming cancer
      cell resistance to standard therapy of the drug were proven. This is the first
      publication describing the influence of Selol 5% on the activity of blood
      antioxidant status in vivo. MATERIALS AND METHODS: We investigated the influence
      of Selol 5% short-term (24h) and long-term (28 days) administration on the
      activity of antioxidant enzymes, including the main selenoenzymes, in healthy
      mice plasma and erythrocytes. Plasma oxygen radical absorbance capacity value
      (ORAC) and the concentration of malonyldialdehyde (MDA) in plasma as a biomarker
      of oxidative stress as well as the value of selenium (Se) concentration in
      erythrocytes were shown. RESULTS: A significant increase of the selenium
      dependent glutathione peroxidase (Se-GSHPx) activity in plasma and erythrocytes,
      plasma selenoprotein P concentration, ORAC values, and Se concentration were
      observed during long-term supplementation as well as after Selol 5% single-dose
      administration, with two distinct increases of activity a few hours after the
      beginning of the experiment and before its end. We found a decreased thioredoxin
      reductase (THRR) activity and an increased MDA level during Selol 5% long-term
      supplementation. Glutathione S-transferase activity (GST) remained unchanged.
      CONCLUSION: Selol 5% supplementation in vivo affects the selenoenzymes activities
      as well as the antioxidant status of plasma and erythrocytes. Selol 5% is an
      inhibitor of thioredoxin reductase activity, which can be important in anticancer
      therapy.

PMID- 24911086
TI  - OATP and MRP2-mediated hepatic uptake and biliary excretion of eprosartan in rat
      and human.
AB  - BACKGROUND: Eprosartan is an angiotensin II receptor antagonist, used in the
      treatment of hypertension and heart failure in clinical patients. The objective
      of this study was to clarify the mechanism underlying hepatic uptake and biliary
      excretion of eprosartan in rats and humans. METHODS: Perfused rat liver in situ,
      rat liver slices, isolated rat hepatocytes and human organic anion-transporting
      polypeptide (OATP)-transfected cells in vitro were used in this study. RESULTS:
      Extraction ratio of eprosartan was decreased by rifampicin in perfused rat
      livers. Uptake of eprosartan in rat liver slices and isolated rat hepatocytes was
      significantly inhibited by Oatp modulators such as ibuprofen, digoxin, rifampicin
      and cyclosporine A, but not by tetraethyl ammonium or p-aminohippurate. Uptake of
      eprosartan in rat hepatocytes indicated a saturable process. Although uptake of
      eprosartan in OATP1B3-human embryonic kidney cells (HEK) 293 cells was not
      observed, significant differences in cellular accumulations of eprosartan between
      vector- and OATP1B1-Madin-Darby canine kidney strain (MDCK) II cells were found
      in transcellular transport study. Moreover, cumulative biliary excretion rate of
      eprosartan in the presence of probenecid (Multidrug resistance-associated protein
      2 (Mrp2) inhibitor) was significantly decreased in perfused rat livers. Vectorial
      basal-to-apical transport of eprosartan was also observed in OATP1B1/MRP2 double
      transfectants. CONCLUSIONS: Eprosartan was transported by multiple Oatps (at
      least Oatp1a1 and Oatp1a4)/Mrp2 in rat and OATP1B1/MRP2, at least, in human.

PMID- 24911087
TI  - The effects of new sigma (sigma) receptor ligands, PB190 and PB212, in the models
      predictive of antidepressant activity.
AB  - BACKGROUND: A number of sigma receptor ligands have been demonstrated to possess
      antidepressant-like effect in some experimental paradigms (e.g. forced swim test,
      tail suspension test, olfactory bulbectomy model, conditioned fear stress). The
      objective of the present study was to find out whether PB190 and PB212, new
      sigma1 receptor ligands, show the effects in some models predictive of
      antidepressant activity. METHODS: The impact of PB190 and PB212 on the immobility
      time in the forced swim test (FST) and tail suspension test (TST) was assessed in
      C57BL/6J male mice. Extracellular bradykinin triggers a transient increase in
      intracellular calcium concentration by activating the phospholipase C/IP3
      pathway. The intracellular calcium concentration was estimated with the dual
      wavelength ratiometric probe Fura-2. RESULTS: In the FST model, PB190 showed a
      moderate antidepressant-like effect (only in the dose of 3mg/kg) which was
      enhanced by joint treatment with amantadine (AMA), 10mg/kg (inactive per se). The
      decrease in the immobility time induced by the combined treatment with PB190 and
      AMA was counteracted by PB212 and by BD1047, a sigma1-receptor antagonist. The in
      vitro studies indicated that Ca(2+)-response was increased by 1MUM PB190, like by
      the sigma1-agonist (+)-pentazocine, while 1 MUM PB212 behaved line sigma1
      antagonist, BD1063. On the other hand, 100 MUM PB190 negatively affected the
      Ca(2+)-response after bradykinin. CONCLUSIONS: The obtained results: 1/indicated
      that in the in vivo conditions PB190 behaved as a sigma1-receptor agonist while
      PB212 counteracted its effect, confirming the in vitro data; 2/gave support to
      the hypothesis that sigma1-receptors might be one of possible mechanisms by which
      drugs induce antidepressant-like activity; 3/revealed that this effect may be
      potentiated by NMDA receptor antagonists, e.g. AMA.

PMID- 24911088
TI  - The effect of lipoate on anaerobic cysteine metabolism in erythrocytes of
      patients treated with peritoneal dialysis.
AB  - BACKGROUND: The studies aimed to evaluate the changes in cysteine sulfur
      metabolism in erythrocytes of end-stage renal failure (ESRF) patients treated
      with continuous ambulatory peritoneal dialysis (CAPD) caused by a one-month
      lipoate (LA) supplementation at a daily dose of 600 mg. METHODS: The level of
      sulfane sulfur and activity of sulfurtransferases were determined in erythrocytes
      of CAPD patients and in the control group. RESULTS: The sulfane sulfur level in
      erythrocytes of CAPD patients did not differ compared with healthy volunteers but
      LA supplementation increased the reactive sulfur concentration. LA elevated also
      cystathionase activity. CONCLUSIONS: LA supplementation in ESRF patients treated
      with CAPD increases the sulfane sulfur level which indicates the augmentation of
      its antioxidant and regulatory properties.

PMID- 24911098
TI  - Sex disparities in neuro-ophthalmologic disorders.
AB  - Many neuro-ophthalmic diseases have a clear sex predilection, which is important
      to recognize in making the diagnosis based on risk stratification and
      understanding the pathogenesis of the disease. This review discusses the more
      common neuro-ophthalmic diseases with a female predilection, including idiopathic
      intracranial hypertension, cerebral venous sinus thrombosis, meningioma, multiple
      sclerosis, migraine, breast-cancer associated neuro-ophthalmic manifestations,
      sarcoidosis, bisphosphonate-associated orbital inflammation, and pregnancy
      related neuro-ophthalmic disorders. In addition, the male predominance in the
      clinical manifestation of Leber's Hereditary Optic Neuropathy is discussed.
      Lastly, the etiology of the sex discrepancies for each disease is explored.

PMID- 24911100
TI  - New phenolic glycosides from Pilea cavaleriei.
AB  - Five new phenolic glycosides, 2-hydroxy-(2'E)-prenyl benzoate-2,4'-di-O-beta-D
      glucopyranoside (1), 2-hydroxy-(2'E)-prenyl benzoate-2-O-alpha-L-arabinopyranosyl
      (1 -> 6)-beta-D-glucopyranoside (2), 4-methylphenol-1-O-alpha-L-rhamnopyranosyl
      (1 -> 6)-beta-D-glucopyranoside (3), 4-methylphenol-1-O-alpha-L-arabinopyranosyl
      (1 -> 6)-beta-D-glucopyranoside (4), and 3,5-dimethoxyphenol-1-O-beta-D
      apiofuranosyl-(1 -> 2)-beta-D-glucopyranoside (5), together with six known
      glycosides (6-11), were isolated from the n-BuOH fraction of the EtOH extract of
      Pilea cavaleriei Levl subsp. cavaleriei. Their structures were elucidated by
      extensive spectroscopic analysis, including 1D and 2D NMR spectroscopy as well as
      HR-ESI-MS, and chemical evidences. All these compounds were isolated from the
      genus Pilea for the first time.

PMID- 24911099
TI  - Modelling Ser129 phosphorylation inhibits membrane binding of pore-forming alpha
      synuclein oligomers.
AB  - BACKGROUND: In several neurodegenerative diseases, hyperphosphorylation at
      position Ser129 is found in fibrillar deposits of alpha-synuclein (asyn),
      implying a pathophysiological role of asyn phosphorylation in neurodegeneration.
      However, recent animal models applying asyn phosphorylation mimics demonstrated a
      protective effect of phosphorylation. Since metal-ion induced asyn oligomers were
      identified as a potential neurotoxic aggregate species with membrane pore-forming
      abilities, the current study was undertaken to determine effects of asyn
      phosphorylation on oligomer membrane binding. METHODS: We investigated the
      influence of S129 phosphorylation on interactions of metal-ion induced asyn
      oligomers with small unilamellar lipid vesicles (SUV) composed of POPC and DPPC
      applying the phosphorylation mimic asyn129E. Confocal single-particle
      fluorescence techniques were used to monitor membrane binding at the single
      particle level. RESULTS: Binding of asyn129E monomers to gel-state membranes
      (DPPC-SUV) is slightly reduced compared to wild-type asyn, while no interactions
      with membranes in the liquid-crystalline state (POPC-SUV) are seen for both asyn
      and asyn129E. Conversely, metal-ion induced oligomer formation is markedly
      increased in asyn129E. Surprisingly, membrane binding to POPC-SUV is nearly
      absent in Fe(3+) induced asyn129E oligomers and markedly reduced in Al(3+)
      induced oligomers. CONCLUSION: The protective effect of pseudophosphorylation
      seen in animal models may be due to impeded oligomer membrane binding.
      Phosphorylation at Ser129 may thus have a protective effect against neurotoxic
      asyn oligomers by preventing oligomer membrane binding and disruption of the
      cellular electrophysiological equilibrium. Importantly, these findings put a new
      complexion on experimental pharmaceutical interventions against POLO-2 kinase.

PMID- 24911103
TI  - GASOLINE: a Greedy And Stochastic algorithm for optimal Local multiple alignment
      of Interaction NEtworks.
AB  - The analysis of structure and dynamics of biological networks plays a central
      role in understanding the intrinsic complexity of biological systems. Biological
      networks have been considered a suitable formalism to extend evolutionary and
      comparative biology. In this paper we present GASOLINE, an algorithm for multiple
      local network alignment based on statistical iterative sampling in connection to
      a greedy strategy. GASOLINE overcomes the limits of current approaches by
      producing biologically significant alignments within a feasible running time,
      even for very large input instances. The method has been extensively tested on a
      database of real and synthetic biological networks. A comprehensive comparison
      with state-of-the art algorithms clearly shows that GASOLINE yields the best
      results in terms of both reliability of alignments and running time on real
      biological networks and results comparable in terms of quality of alignments on
      synthetic networks. GASOLINE has been developed in Java, and is available, along
      with all the computed alignments, at the following URL:
      http://ferrolab.dmi.unict.it/gasoline/gasoline.html. 

PMID- 24911105
TI  - Recent blood pressure guidelines: making sense of the controversy.

PMID- 24911106
TI  - Depression among patients with acute coronary syndromes.

PMID- 24911101
TI  - Plant, animal, and fungal micronutrient queuosine is salvaged by members of the
      DUF2419 protein family.
AB  - Queuosine (Q) is a modification found at the wobble position of tRNAs with GUN
      anticodons. Although Q is present in most eukaryotes and bacteria, only bacteria
      can synthesize Q de novo. Eukaryotes acquire queuine (q), the free base of Q,
      from diet and/or microflora, making q an important but under-recognized
      micronutrient for plants, animals, and fungi. Eukaryotic type tRNA-guanine
      transglycosylases (eTGTs) are composed of a catalytic subunit (QTRT1) and a
      homologous accessory subunit (QTRTD1) forming a complex that catalyzes q
      insertion into target tRNAs. Phylogenetic analysis of eTGT subunits revealed a
      patchy distribution pattern in which gene losses occurred independently in
      different clades. Searches for genes co-distributing with eTGT family members
      identified DUF2419 as a potential Q salvage protein family. This prediction was
      experimentally validated in Schizosaccharomyces pombe by confirming that Q was
      present by analyzing tRNA(Asp) with anticodon GUC purified from wild-type cells
      and by showing that Q was absent from strains carrying deletions in the QTRT1 or
      DUF2419 encoding genes. DUF2419 proteins occur in most Eukarya with a few
      possible cases of horizontal gene transfer to bacteria. The universality of the
      DUF2419 function was confirmed by complementing the S. pombe mutant with the Zea
      mays (maize), human, and Sphaerobacter thermophilus homologues. The enzymatic
      function of this family is yet to be determined, but structural similarity with
      DNA glycosidases suggests a ribonucleoside hydrolase activity. 

PMID- 24911107
TI  - 20 things you didn't know about European cardiac nurses.

PMID- 24911108
TI  - Go with the flow: progress in mechanical circulatory support.

PMID- 24911110
TI  - Acoustic dynamics of supercooled indomethacin probed by Brillouin light
      scattering.
AB  - Acoustics dynamics of the molecular glass-former indomethacin (IMC) have been
      investigated by Brillouin light scattering (BLS) at GHz frequencies. Elastic
      response of the system has been tracked from the melting temperature down to the
      glass transition through the supercooled liquid. Both the structural arrest and
      the vibrational dynamics are described by modeling the experimentally determined
      dynamic structure factor within the framework of the Langevin equation, through a
      simplified choice of memory function which allows one to determine sound velocity
      and the acoustic attenuation coefficient as a function of temperature. The
      density fluctuation spectra in the glassy phase, as probed by BLS, are compared
      with time-domain results from photoacoustics experiments. The arising scenario is
      discussed in the context of current literature reporting inelastic X-ray
      scattering and BLS in platelet geometry. The link between the probed elastic
      properties and the non-ergodicity factor of the glass phase is finally
      scrutinized. 

PMID- 24911111
TI  - Is gynaecological laparoscopic surgery safe for elderly women? A comparison
      study.
AB  - The aim of this study was to evaluate the efficacy and safety of gynaecological
      laparoscopic surgery in an elderly group, by comparing the operative outcomes of
      the elderly group with those of the younger group. We analysed retrospective data
      of 121 women who underwent laparoscopic surgery for benign gynaecological
      disease. Women aged > 60 years were compared with women aged between 30 and 50
      years who had the same operation. We evaluated body mass index, comorbidities,
      number of previous abdominal surgeries, operating time, haemoglobin change,
      postoperative complications, hospital stay and return of bowel activity. There
      were no significant differences between the elderly and a matched younger group
      in number of previous abdominal surgeries, operating time, ASA score
      distribution, changes in haemoglobin level, hospital stay and postoperative
      complications (p > 0.05). Laparoscopic surgery can be safely performed in elderly
      patients with benign gynaecological disease, and surgeons should not hesitate to
      perform laparoscopic surgery in elderly patients.

PMID- 24911112
TI  - Anodic stripping tin titration: a method for the voltammetric determination of
      platinum at trace levels.
AB  - We propose here a novel voltammetric method for the determination of platinum at
      trace levels. The method is based on the interference that platinum generates on
      the anodic stripping signal of tin acidic solutions: in appropriate conditions
      platinum uses the intermediate formation of tin(II) ions, taking place during the
      tin cathodic reduction, to reduce itself and to form mixed Pt(II)-Sn(II) chloro
      complexes. From the analysis of the anodic stripping plots obtained after
      subsequent additions of tin in a Pt-containing solution, it is possible to
      quantify accurately and precisely the Pt concentration from 3 ppb to more than 10
      ppm. This novel method is validated for the analysis of Pt in heterogeneous
      catalysts, but in principle could be extended to other matrixes. 

PMID- 24911109
TI  - Coumestan inhibits radical-induced oxidation of DNA: is hydroxyl a necessary
      functional group?
AB  - Coumestan is a natural tetracycle with a C?C bond shared by a coumarin moiety and
      a benzofuran moiety. In addition to the function of the hydroxyl group on the
      antioxidant activity of coumestan, it is worth exploring the influence of the
      oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven
      coumestans containing electron-withdrawing and electron-donating groups were
      synthesized to evaluate the abilities to trap 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(*+)), 2,2'-diphenyl-1
      picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to
      inhibit the oxidations of DNA mediated by (*)OH, Cu(2+)/glutathione (GSH), and
      2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. It was found
      that all of the coumestans used herein can quench the aforementioned radicals and
      can inhibit (*)OH-, Cu(2+)/GSH-, and AAPH-induced oxidations of DNA. In
      particular, substituent-free coumestan exhibits higher ability to quench DPPH and
      to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted
      coumestan shows a similar ability to inhibit (*)OH- and Cu(2+)/GSH-induced
      oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of
      the coumestan can be attributed to the lactone in the coumarin moiety and,
      therefore, a hydroxyl group may not be a necessary functional group for coumestan
      to be an antioxidant. 

PMID- 24911114
TI  - Dual roles of sulfonyl hydrazides: a three-component reaction to construct fully
      substituted pyrazoles using TBAI/TBHP.
AB  - A mild and rapid approach has been developed for the construction of fully
      substituted pyrazoles using TBAI as a catalyst and TBHP as an oxidant, in which
      tosylhydrazide functions as the ring component and sulfonyl precursor. This
      protocol features a wide substrate scope with a broad range of functional group
      tolerance, utilizes easily available starting materials, can be scaled-up, and is
      operationally simple. 

PMID- 24911113
TI  - Simultaneous detection of deoxyadenosine and deoxyguanosine adducts in the tongue
      and other oral tissues of mice treated with Dibenzo[a,l]pyrene.
AB  - We were the first to demonstrate that direct application of the environmental
      pollutant and tobacco smoke constituent dibenzo[a,l]pyrene (DB[a,l]P) into the
      oral cavity of mice induced squamous cell carcinoma (SCC) in oral tissues but not
      in the tongue; however, the mechanisms that can account for the varied
      carcinogenicity remain to be determined. Furthermore, we also showed that not
      only dA adducts, but also dG adducts can account for the mutagenic activity of
      DB[a,l]P in the oral tissues in vivo. In this study, we initially focused on
      DB[a,l]P-induced genotoxic effects in both oral and tongue tissues. Therefore, to
      fully assess the contribution of these DNA adducts in the initiation stage of
      carcinogenesis induced by DB[a,l]P, an LC-MS/MS method to simultaneously detect
      and quantify DB[a,l]PDE-dG and -dA adducts was developed. Mice were orally
      administered with DB[a,l]P (24 nmole, 3 times per week for 5 weeks) or its fjord
      region diol epoxide, (+/-)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14
      tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE, 12 nmole, single application); animals
      were sacrificed at 2, 7, 14, and 28 days after the last dose of carcinogen
      administration. Oral and tongue tissues were obtained and DNA were isolated
      followed by enzymatic hydrolysis. Following the development of an isotope
      dilution LC-MS/MS method, we successfully detected (-)-anti-cis- and (-)-anti
      trans-DB[a,l]PDE-N(2)-dG, as well as (-)-anti-cis- and (-)-anti-trans-DB[a,l]PDE
      N(6)-dA in oral and tongue tissues of mice treated with DB[a,l]P. Levels of (-)
      anti-trans-DB[a,l]PDE-N(6)-dA were >=2 folds higher than (-)-anti-cis-DB[a,l]PDE
      N(6)-dA adduct and those of dG adducts in the oral tissues and tongue at all time
      points selected after the cessation of DB[a,l]P treatment. Levels of dG adducts
      were comparable in both tissues. Collectively, our results support that DB[a,l]P
      is predominantly metabolized to (-)-anti-DB[a,l]PDE, and the levels and
      persistence of (-)-anti-trans-DB[a,l]PDE-N(6)-dA may, in part, explain the
      carcinogenicity of DB[a,l]P in the oral tissues but not in the tongue. 

PMID- 24911115
TI  - The built environment, physical activity, and aging in the United States: a state
      of the science review.

PMID- 24911116
TI  - Substituent effects on the kinetics of bifunctional styrene SAM formation on H
      terminated Si.
AB  - Self-assembled monolayers (SAMs) on metal and semiconductor surfaces are of
      interest in electronic devices, molecular and biosensors, and nanostructured
      surface preparation. Bifunctionalized molecules, where one functional group
      attaches to the surface while the other remains free for further modification,
      allow for the rational design of multilayer chemisorbed thin films. In this
      study, substituted styrenes acted as a model system for SAM formation through an
      alkene moiety. Substituents ranging from activating to strongly deactivating for
      aromatic reactions were used to probe the effect of the electronic properties of
      functionalizing molecules on the rate of SAM formation. Substituted styrene SAMs
      were formed on hydrogen-terminated p-type Si(100) and n-type Si(111) via
      sonochemical functionalization. Monolayers were characterized via ellipsometry,
      IR spectroscopy, contact angle goniometry, and X-ray photoelectron spectroscopy
      (XPS). Initial rates of reaction for molecules that selectively attached through
      the alkene were further studied. A linear relationship was observed between the
      initial rates of surface functionalization and the substituent electron
      donating/withdrawing ability for the substituted styrenes, as described by their
      respective Hammett constants. This study provides precedent for applying well
      quantified homogeneous chemical reaction relationships to reactions at the solid
      liquid interface. 

PMID- 24911117
TI  - Psychosocial factors related to posttraumatic growth in breast cancer survivors:
      a review.
AB  - In this article, we reviewed quantitative studies regarding psychosocial factors
      associated with posttraumatic growth (PTG) in patients with breast cancer to
      elucidate our understanding of a model of PTG process. PsycInfo, Embase, Medline,
      Web of Knowledge were used for the search. Only quantitative, English written
      studies that used the Posttraumatic Growth Inventory (PTGI) measure administered
      to breast cancer patients were included. The initial search yielded 90
      publications. Of those, 22 studies satisfied inclusion criteria and formed the
      basis of the review. Personality traits (e.g., optimism and openness), cognitive
      processing of cancer (e.g., deliberate rumination), perceived threat of the
      disease, coping strategies (e.g., problem-focused), and social support were
      identified to be related to PTG in women with breast cancer. Demographic
      characteristics (e.g., age at cancer diagnosis) were also found to play a key
      role in PTG. The findings of this review provided support to Tedeschi and
      Calhoun's functional-descriptive model of PTG process. Further directions for
      research and clinical implications are provided. 

PMID- 24911118
TI  - Joseph Alouf (1929-2014).

PMID- 24911119
TI  - PRMT2 and RORgamma expression are associated with breast cancer survival
      outcomes.
AB  - Protein arginine methyltransferases (PRMTs) methylate arginine residues on
      histones and target transcription factors that play critical roles in many
      cellular processes, including gene transcription, mRNA splicing, proliferation,
      and differentiation. Recent studies have linked PRMT-dependent epigenetic marks
      and modifications to carcinogenesis and metastasis in cancer. However, the role
      of PRMT2-dependent signaling in breast cancer remains obscure. We demonstrate
      PRMT2 mRNA expression was significantly decreased in breast cancer relative to
      normal breast. Gene expression profiling, Ingenuity and protein-protein
      interaction network analysis after PRMT2-short interfering RNA transfection into
      MCF-7 cells, revealed that PRMT2-dependent gene expression is involved in cell
      cycle regulation and checkpoint control, chromosomal instability, DNA repair, and
      carcinogenesis. For example, PRMT2 depletion achieved the following: 1) increased
      p21 and decreased cyclinD1 expression in (several) breast cancer cell lines, 2)
      decreased cell migration, 3) induced an increase in nucleotide excision repair
      and homologous recombination DNA repair, and 4) increased the probability of
      distance metastasis free survival (DMFS). The expression of PRMT2 and retinoid
      related orphan receptor-gamma (RORgamma) is inversely correlated in estrogen
      receptor-positive breast cancer and increased RORgamma expression increases DMFS.
      Furthermore, we found decreased expression of the PRMT2-dependent signature is
      significantly associated with increased probability of DMFS. Finally, weighted
      gene coexpression network analysis demonstrated a significant correlation between
      PRMT2-dependent genes and cell-cycle checkpoint, kinetochore, and DNA repair
      circuits. Strikingly, these PRMT2-dependent circuits are correlated with pan
      cancer metagene signatures associated with epithelial-mesenchymal transition and
      chromosomal instability. This study demonstrates the role and significant
      correlation between a histone methyltransferase (PRMT2)-dependent signature,
      RORgamma, the cell-cycle regulation, DNA repair circuits, and breast cancer
      survival outcomes. 

PMID- 24911122
TI  - Aspiration-related lung diseases.
AB  - Aspiration is a common but underrecognized clinicopathologic entity, with varied
      radiographic manifestations. Aspiration represents a spectrum of diseases,
      including diffuse aspiration bronchiolitis, aspiration pneumonitis, airway
      obstruction by foreign body, exogenous lipoid pneumonia, interstitial fibrosis,
      and aspiration pneumonia with or without lung abscess formation. Many patients
      who aspirate do not present with disease, suggesting that pathophysiology is
      related to a variety of factors, including decreased levels of consciousness,
      dysphagia, impaired mucociliary clearance, composition of aspirate, and impaired
      host defenses. In this pictorial essay, we will review the different types of
      aspiration lung diseases, focusing on their imaging features and differential
      diagnosis. 

PMID- 24911121
TI  - Norwegian deep-water coral reefs: cultivation and molecular analysis of
      planktonic microbial communities.
AB  - Deep-sea coral reefs do not receive sunlight and depend on plankton. Little is
      known about the plankton composition at such reefs, even though they constitute
      habitats for many invertebrates and fish. We investigated plankton communities
      from three reefs at 260-350 m depth at hydrocarbon fields off the mid-Norwegian
      coast using a combination of cultivation and small subunit (SSU) rRNA gene and
      transcript sequencing. Eight months incubations of a reef water sample with
      minimal medium, supplemented with carbon dioxide and gaseous alkanes at in situ
      like conditions, enabled isolation of mostly Alphaproteobacteria (Sulfitobacter,
      Loktanella), Gammaproteobacteria (Colwellia) and Flavobacteria (Polaribacter).
      The relative abundance of isolates in the original sample ranged from ~ 0.01% to
      0.80%. Comparisons of bacterial SSU sequences from filtered plankton of reef and
      non-reef control samples indicated high abundance and metabolic activity of
      primarily Alphaproteobacteria (SAR11 Ia), Gammaproteobacteria (ARCTIC96BD-19),
      but also of Deltaproteobacteria (Nitrospina, SAR324). Eukaryote SSU sequences
      indicated metabolically active microalgae and animals, including codfish, at the
      reef sites. The plankton community composition varied between reefs and differed
      between DNA and RNA assessments. Over 5000 operational taxonomic units were
      detected, some indicators of reef sites (e.g. Flavobacteria, Cercozoa,
      Demospongiae) and some more active at reef sites (e.g. Gammaproteobacteria,
      Ciliophora, Copepoda).

PMID- 24911120
TI  - Minireview: Thioredoxin-interacting protein: regulation and function in the
      pancreatic beta-cell.
AB  - Pancreatic beta-cells are responsible for insulin production, and loss of
      functional beta-cell mass is now recognized as a critical step in the
      pathogenesis of both type 1 and type 2 diabetes. However, the factors controlling
      the life and death of the pancreatic beta-cell have only started to be
      elucidated. Discovered as the top glucose-induced gene in a human islet
      microarray study 12 years ago, thioredoxin-interacting protein (TXNIP) has now
      emerged as such a key player in pancreatic beta-cell biology. Since then, beta
      cell expression of TXNIP has been found to be tightly regulated by multiple
      factors and to be dramatically increased in diabetic islets. Elevated TXNIP
      levels induce beta-cell apoptosis, whereas TXNIP deficiency protects against type
      1 and type 2 diabetes by promoting beta-cell survival. TXNIP interacts with and
      inhibits thioredoxin and thereby controls the cellular redox state, but it also
      belongs to the alpha-arrestin family of proteins and regulates a variety of
      metabolic processes. Most recently, TXNIP has been discovered to control beta
      cell microRNA expression, beta-cell function, and insulin production. In this
      review, the current state of knowledge regarding regulation and function of TXNIP
      in the pancreatic beta-cell and the implications for drug development are
      discussed. 

PMID- 24911123
TI  - Association of marketing interactions with medical trainees' knowledge about
      evidence-based prescribing: results from a national survey.
AB  - IMPORTANCE: In recent years, numerous US medical schools and academic medical
      centers have enacted policies preventing pharmaceutical sales representatives
      from interacting directly with students. Little is known about how pharmaceutical
      sales representatives affect trainees' knowledge about pharmaceutical
      prescribing. OBJECTIVE: To determine whether there is an association between
      medical trainees' interactions with pharmaceutical promotion and their
      preferences in medication use. DESIGN, SETTING, AND PARTICIPANTS: We surveyed a
      nationally representative sample of first- and fourth-year medical students and
      third-year residents by randomly selecting at least 14 trainees at each level per
      school. EXPOSURES: All trainees were asked how often they used different
      educational resources to learn about prescription drugs. Among fourth-year
      students and residents, we posed a series of multiple choice knowledge questions
      asking about the appropriate initial therapy for clinical scenarios involving
      patients with diabetes, hyperlipidemia, hypertension, and difficulty sleeping.
      MAIN OUTCOMES AND MEASURES: Evidence-based answers followed widely used clinical
      guidelines, while marketed-drug answers favored brand-name drugs over generic
      alternatives. We used survey answers to build an industry relations index
      assessing each trainee's level of acceptance of pharmaceutical promotion; we used
      proportional odds logistic regression models to estimate the association between
      the index and responses to the knowledge questions. RESULTS: The 1601 student
      (49.0% response rate) and 735 resident (42.9% response rate) respondents reported
      common use of unfiltered sources of drug information such as Google (74.2%-88.9%)
      and Wikipedia (45.2%-84.5%). We found that 48% to 90% of fourth-year students and
      residents accurately identified evidence-based prescribing choices. A 10-point
      higher industry relations index was associated with 15% lower odds of selecting
      an evidence-based prescribing choice (odds ratio [OR], 0.85; 95% CI, 0.79-0.92)
      (P < .001). There was also a significant association between the industry
      relations index and greater odds of choosing to prescribe brand-name drugs (OR,
      1.08; 95% CI, 1.00-1.16) (P = .04). CONCLUSIONS AND RELEVANCE: Among physician
      trainees, our survey showed an association between positive attitudes toward
      industry-physician interactions and less knowledge about evidence-based
      prescribing and greater inclination to recommend brand-name drugs. Policies
      intended to insulate trainees from pharmaceutical marketing may promote better
      educational outcomes.

PMID- 24911126
TI  - Methylation analysis in newborn screening for fragile X syndrome.

PMID- 24911127
TI  - Methylation analysis in newborn screening for fragile X syndrome--reply.

PMID- 24911128
TI  - Medulloblastoma and dizziness.

PMID- 24911129
TI  - Medulloblastoma and dizziness--reply.

PMID- 24911130
TI  - Intrathecal gadolinium for magnetic resonance myelography in spontaneous
      intracranial hypotension: valuable but may be risky.

PMID- 24911131
TI  - Intrathecal gadolinium for magnetic resonance myelography in spontaneous
      intracranial hypotension: valuable but may be risky--reply.

PMID- 24911135
TI  - Type I error inflation in the traditional by-participant analysis to metamemory
      accuracy: a generalized mixed-effects model perspective.
AB  - In order to examine metacognitive accuracy (i.e., the relationship between
      metacognitive judgment and memory performance), researchers often rely on by
      participant analysis, where metacognitive accuracy (e.g., resolution, as measured
      by the gamma coefficient or signal detection measures) is computed for each
      participant and the computed values are entered into group-level statistical
      tests such as the t test. In the current work, we argue that the by-participant
      analysis, regardless of the accuracy measurements used, would produce a
      substantial inflation of Type I error rates when a random item effect is present.
      A mixed-effects model is proposed as a way to effectively address the issue, and
      our simulation studies examining Type I error rates indeed showed superior
      performance of mixed-effects model analysis as compared to the conventional by
      participant analysis. We also present real data applications to illustrate
      further strengths of mixed-effects model analysis. Our findings imply that
      caution is needed when using the by-participant analysis, and recommend the mixed
      effects model analysis.

PMID- 24911134
TI  - Enantioselective intramolecular propargylic amination using chiral copper-pybox
      complexes as catalysts.
AB  - Intramolecular propargylic amination of propargylic acetates bearing an amino
      group at the suitable position in the presence of chiral copper-pybox complexes
      proceeds enantioselectively to give optically active 1-ethynyl-isoindolines (up
      to 98% ee). The method described in this communication provides a useful
      synthetic approach to the enantioselective preparation of nitrogen containing
      heterocyclic compounds with an ethynyl group at the alpha-position. 

PMID- 24911137
TI  - The impact of disablers on predictive inference.
AB  - People consider alternative causes when deciding whether a cause is responsible
      for an effect (diagnostic inference) but appear to neglect them when deciding
      whether an effect will occur (predictive inference). Five experiments were
      conducted to test a 2-part explanation of this phenomenon: namely, (a) that
      people interpret standard predictive queries as requests to estimate the
      probability of the effect in the presence of the cause alone, which renders
      alternative causes irrelevant, and (b) that the impact of disablers (inhibitory
      causes) on predictive judgments is underestimated, and this underestimation is
      wrongly interpreted as cause neglect. Experiment 1 showed that standard
      predictive queries are frequently interpreted as requests to estimate the
      likelihood of E given C alone. In Experiment 2, a causal Bayes network
      overestimated predictive inference when it was queried in the standard way, but
      this overestimation diminished when predictive inference was queried using an
      alternative wording. In Experiment 3, participants judged alternative causes to
      be relevant to diagnostic inference and both disablers and alternative causes to
      be relevant to predictive inference. In Experiment 4, disablers greatly
      overshadowed alternative causes in predictive judgments, but their impact on
      diagnostic judgments was negligible. In Experiment 5, the order of disabler
      retrieval influenced causal judgments. Taken together, these results indicate
      that human causal inference cannot be adequately modeled unless the manner in
      which knowledge is retrieved and applied is taken into consideration.

PMID- 24911136
TI  - Conjunction illusions and conjunction fallacies in episodic memory.
AB  - Recent research on the overdistribution principle implies that episodic memory is
      infected by conjunction illusions. These are instances in which an item that was
      presented in a single context (e.g., List 1) is falsely remembered as having been
      presented in multiple contexts (e.g., List 1 and List 2). Robust conjunction
      illusions were detected in source-monitoring designs in which conjunctive probes
      ("Was bagpipe presented on List 1 and List 2?") were added to the traditional
      nonconjunctive probes ("Was bagpipe presented on List 1?"). In Experiment 1, the
      levels of those illusions were comparable to what would be expected on the basis
      of results from prior overdistribution experiments. In Experiments 2 and 3,
      conjunction illusions were neither eliminated nor reduced by a manipulation that
      should have had such effects if the illusions are by-products of subjective
      differences in retrieved memory support. Also, conjunction illusions sometimes
      rose to the level of conjunction fallacies: In certain conditions, subjects
      thought that items were more likely to have occurred in all the presentation
      contexts than in any single context, which is impossible. Two general approaches
      to explaining overdistribution, representational accounts and retrieval accounts,
      are considered.

PMID- 24911138
TI  - Reliability and validity of sports accelerometers during static and dynamic
      testing.
AB  - PURPOSE: To investigate the validity and reliability of accelerometry of the SPI
      ProX II dual data logger (GPSports, Canberra, Australia). METHODS: Controlled
      laboratory assessments determined the accuracy and reproducibility of raw
      accelerometer data. Intra- and interdevice reliability assessed the ability of
      the SPI-ProX II accelerometers to repeatedly measure peak gravitational
      accelerations (g) during impact-based testing. Static and dynamic validity
      testing assessed the accuracy of SPI-ProX II accelerometers against a criterion
      referenced accelerometer. Dynamic validity was assessed over a range of
      frequencies from 5 to 15 Hz. RESULTS: Intradevice reliability found no
      differences (P < .05) between 4 SPI-ProX II accelerometers, with a low
      coefficient of variation (1.87-2.21%). SPI-ProX II accelerometers demonstrated
      small to medium effect-size (ES) differences (0.10-0.44) between groups and
      excellent interdevice reliability, with no difference found between units (F =
      0.826, P = .484). Validity testing revealed significant differences between
      devices (P = .001), with high percentage differences (27.5-30.5%) and a large ES
      (>3.44). CONCLUSIONS: SPI-ProX II accelerometers demonstrated excellent intra-
      and interaccelerometer reliability. However, static and dynamic validity were
      poor, and caution is recommended when measuring the absolute magnitude of
      acceleration, particularly for high-frequency movements. Regular assessment of
      individual devices is advised, particularly for mechanical damage and signal
      drift errors. It is recommended that guidelines be provided by the manufacturer
      on measuring shifts in the base accelerometer signal, including time frames for
      assessing accelerometer axis, magnitude of errors, and calibration of
      accelerometers from a stable reference point.

PMID- 24911139
TI  - Nuclear quadrupole coupling constants of two chemically distinct nitrogen atoms
      in 4-aminobenzonitrile.
AB  - The rotational spectrum of 4-aminobenzonitrile in the gas phase between 2 and 8.5
      GHz is reported. Due to the two chemically distinct nitrogen atoms, the observed
      transitions showed a rich hyperfine structure. From the determination of the
      nuclear quadrupole coupling constants, information about the electronic
      environment of these atoms could be inferred. The results are compared to data
      for related molecules, especially with respect to the absence of dual
      fluorescence in 4-aminobenzonitrile. In addition, the two-photon ionization
      spectrum of this molecule was recorded using a time-of-flight mass spectrometer
      integrated into the setup. This new experimental apparatus is presented here for
      the first time. 

PMID- 24911141
TI  - The effect of black raspberry extracts on MnSOD activity in protection against
      concanavalin A induced liver injury.
AB  - Inflammation and oxidative stress are the key events in carcinogenetic
      transformation. Black raspberries (BRB) have been demonstrated to have
      antioxidant, antiinflammatory and anticancer bioactivities. In this study, a
      concanavalin A induced hepatitis mouse model is used to examine the effect of BRB
      extract on hepatic injury. Three BRB extracts, including ethanol/H2O extracts
      (both anthocyanin-contained fraction and nonanthocyanin-contained fraction) and
      hexane extract were used. The alterations in hepatic histology, apoptosis, and
      oxidative stress were observed in the animals pretreated with BRB extracts and
      then challenged by concanavalin A. Results indicate that ethanol/H2O extracts can
      inhibit Con A induced liver injury. The hepatic protection by the ethanol/H2O BRB
      extracts is associated with decreases of lipid peroxidation and NDA oxidative
      damage. Importantly, the BRB extracts increase manganese superoxide dismutase
      (MnSOD) activity but not the CuZnSOD. The preservation of MnSOD by BRB extracts
      is associated with the protective action in the liver challenged by Con A.
      Ethanol/H2O BRB extracts function as antioxidants, thus demonstrating the
      critical role of oxidative stress in the Con A induced liver injury, and
      providing evidence that the protective effects of ethanol/H2O BRB extracts
      result, at least in part, from their antioxidant action. 

PMID- 24911142
TI  - Comparison of in silico models for prediction of Daphnia magna acute toxicity.
AB  - Eight in silico modelling packages were evaluated and compared for the prediction
      of Daphnia magna acute toxicity from the viewpoint of the European legislation on
      chemicals, REACH. We tested the following models: Discovery Studio (DS) TOPKAT,
      ACD/Tox Suite, ADMET Predictor, ECOSAR (Ecological Structure Activity
      Relationships), TerraQSAR, T.E.S.T. (Toxicity Estimation Software Tool) and two
      models implemented in VEGA on 480 industrial compounds for 48-h median lethal
      concentrations (LC50) to D. magna, matching them with experimental values. The
      quality of the estimates was compared using a standard statistical review and an
      additional classification approach in which the hazard predictions were grouped
      using well-defined regulatory criteria. The regression parameters, correlation
      coefficient being the most influential, showed that four models (ADMET Predictor,
      DS TOPKAT, TerraQSAR and VEGA DEMETRA) had similar reliability. These performed
      better than the others, but the coefficient of determination was still low (r2
      around 0.6), considering that at least half the predicted compounds were inside
      the training sets. Additionally, we grouped the results in four defined toxicity
      classes. TerraQSARTM gave 60% of correct classifications, followed by DS TOPKAT,
      ADMET PredictorTM and VEGA DEMETRA, with 56%, 54% and 48%, respectively. These
      results highlight the challenges associated with developing reliable and easily
      applied acceptability criteria for the regulatory use of QSAR models to D. magna
      acute toxicity.

PMID- 24911143
TI  - Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic
      progenitors.
AB  - Ewing's sarcoma is a highly malignant bone tumor found in children and
      adolescents, and the origin of this malignancy is not well understood. Here, we
      introduced a Ewing's sarcoma-associated genetic fusion of the genes encoding the
      RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a
      fraction of cells enriched for osteochondrogenic progenitors derived from the
      embryonic superficial zone (eSZ) of long bones collected from late gestational
      murine embryos. EWS-ETS fusions efficiently induced Ewing's sarcoma-like small
      round cell sarcoma formation by these cells. Analysis of the eSZ revealed a
      fraction of a precursor cells that express growth/differentiation factor 5
      (Gdf5), the transcription factor Erg, and parathyroid hormone-like hormone
      (Pthlh), and selection of the Pthlh-positive fraction alone further enhanced EWS
      ETS-dependent tumor induction. Genes downstream of the EWS-ETS fusion protein
      were quite transcriptionally active in eSZ cells, especially in regions in which
      the chromatin structure of the ETS-responsive locus was open. Inhibition of beta
      catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2
      (EZH2) suppressed cell growth in a murine model of Ewing's sarcoma, suggesting
      the utility of the current system as a preclinical model. These results indicate
      that eSZ cells are highly enriched in precursors to Ewing's sarcoma and provide
      clues to the histogenesis of Ewing's sarcoma in bone. 

PMID- 24911145
TI  - Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging.
AB  - The number of newly formed neurons declines rapidly during aging, and this
      decrease in neurogenesis is associated with decreased function of neural
      stem/progenitor cells (NPCs). Here, we determined that a WIP1-dependent pathway
      regulates NPC differentiation and contributes to the age-associated decline of
      neurogenesis. Specifically, we found that WIP1 is expressed in NPCs of the mouse
      subventricular zone (SVZ) and aged animals with genetically enhanced WIP1
      expression exhibited higher NPC numbers and neuronal differentiation compared
      with aged WT animals. Additionally, augmenting WIP1 expression in aged animals
      markedly improved neuron formation and rescued a functional defect in fine odor
      discrimination in aged mice. We identified the WNT signaling pathway inhibitor
      DKK3 as a key downstream target of WIP1 and found that expression of DKK3 in the
      SVZ is restricted to NPCs. Using murine reporter strains, we determined that DKK3
      inhibits neuroblast formation by suppressing WNT signaling and Dkk3 deletion or
      pharmacological activation of the WNT pathway improved neuron formation and
      olfactory function in aged mice. We propose that WIP1 controls DKK3-dependent
      inhibition of neuronal differentiation during aging and suggest that regulating
      WIP1 levels could prevent certain aspects of functional decline of the aging
      brain. 

PMID- 24911144
TI  - Vitamin B12-dependent taurine synthesis regulates growth and bone mass.
AB  - Both maternal and offspring-derived factors contribute to lifelong growth and
      bone mass accrual, although the specific role of maternal deficiencies in the
      growth and bone mass of offspring is poorly understood. In the present study, we
      have shown that vitamin B12 (B12) deficiency in a murine genetic model results in
      severe postweaning growth retardation and osteoporosis, and the severity and time
      of onset of this phenotype in the offspring depends on the maternal genotype.
      Using integrated physiological and metabolomic analysis, we determined that B12
      deficiency in the offspring decreases liver taurine production and associates
      with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis.
      Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently
      enhanced osteoblast function, and in B12-deficient offspring, oral administration
      of taurine rescued their growth retardation and osteoporosis phenotypes. These
      results identify B12 as an essential vitamin that positively regulates
      postweaning growth and bone formation through taurine synthesis and suggests
      potential therapies to increase bone mass. 

PMID- 24911147
TI  - MicroRNA-205 signaling regulates mammary stem cell fate and tumorigenesis.
AB  - Dysregulation of epigenetic controls is associated with tumorigenesis in response
      to microenvironmental stimuli; however, the regulatory pathways involved in
      epigenetic dysfunction are largely unclear. We have determined that a critical
      epigenetic regulator, microRNA-205 (miR-205), is repressed by the ligand jagged1,
      which is secreted from the tumor stroma to promote a cancer-associated stem cell
      phenotype. Knockdown of miR-205 in mammary epithelial cells promoted epithelial
      mesenchymal transition (EMT), disrupted epithelial cell polarity, and enhanced
      symmetric division to expand the stem cell population. Furthermore, miR-205
      deficient mice spontaneously developed mammary lesions, while activation of miR
      205 markedly diminished breast cancer stemness. These data provide evidence that
      links tumor microenvironment and microRNA-dependent regulation to disruption of
      epithelial polarity and aberrant mammary stem cell division, which in turn leads
      to an expansion of stem cell population and tumorigenesis. This study elucidates
      an important role for miR-205 in the regulation of mammary stem cell fate,
      suggesting a potential therapeutic target for limiting breast cancer genesis. 

PMID- 24911146
TI  - CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor
      resistance.
AB  - The majority of non-small cell lung cancer (NSCLC) patients harbor EGFR
      activating mutations that can be therapeutically targeted by EGFR tyrosine kinase
      inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset
      of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR
      inhibitors reportedly involves SRC activation and induction of epithelial-to
      mesenchymal transition (EMT). Here, we have demonstrated that overexpression of
      CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI-sensitive and EGFR
      mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft
      models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations
      that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1
      compared with tumors from patients that were sensitive to EGFR-TKIs. Primary
      NSCLC cells derived from a patient with EGFR-mutated NSCLC that was intrinsically
      erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon
      loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to
      promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion
      induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent
      ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced
      erlotinib resistance was directly mediated through SRC but not ZEB1; therefore,
      cotargeting EGFR and SRC synergistically attenuated growth of erlotinib
      resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo,
      suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance
      in patients with CRIPTO1-positive, EGFR-mutated NSCLC. 

PMID- 24911148
TI  - Umbilical cord blood expansion with nicotinamide provides long-term multilineage
      engraftment.
AB  - BACKGROUND: Delayed hematopoietic recovery is a major drawback of umbilical cord
      blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens
      time to hematopoietic recovery, but long-term, robust engraftment by the expanded
      unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell
      product consisting of stem cells expanded for 21 days in the presence of
      nicotinamide and a noncultured T cell fraction (NiCord) can accelerate
      hematopoietic recovery and provide long-term engraftment. METHODS: In a phase I
      trial, 11 adults with hematologic malignancies received myeloablative bone marrow
      conditioning followed by transplantation with NiCord and a second unmanipulated
      UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and
      compared with historical controls. RESULTS: No adverse events were attributable
      to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment
      derived from NiCord was observed in 8 patients, and NiCord engraftment remained
      stable in all patients, with a median follow-up of 21 months. Two patients
      achieved long-term engraftment with the unmanipulated unit. Patients transplanted
      with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P <
      0.001) compared with that seen in historical controls. The 1-year overall and
      progression-free survival rates were 82% and 73%, respectively. CONCLUSION: UCB
      derived hematopoietic stem and progenitor cells expanded in the presence of
      nicotinamide and transplanted with a T cell-containing fraction contain both
      short-term and long-term repopulating cells. The results justify further study of
      NiCord transplantation as a single UCB graft. If long-term safety is confirmed,
      NiCord has the potential to broaden accessibility and reduce the toxicity of UCB
      transplantation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01221857. FUNDING:
      Gamida Cell Ltd.

PMID- 24911149
TI  - Characterization of pandemic influenza immune memory signature after vaccination
      or infection.
AB  - The magnitude, quality, and maintenance of immunological memory after infection
      or vaccination must be considered for future design of effective influenza
      vaccines. In 2009, the influenza pandemic produced disease that ranged from mild
      to severe, even fatal, illness in infected healthy adults and led to vaccination
      of a portion of the population with the adjuvanted, inactivated influenza
      A(H1N1)pdm09 vaccine. Here, we have proposed a multiparameter quantitative and
      qualitative approach to comparing adaptive immune memory to influenza 1 year
      after mild or severe infection or vaccination. One year after antigen encounter,
      severely ill subjects maintained high levels of humoral and polyfunctional
      effector/memory CD4+ T cells responses, while mildly ill and vaccinated subjects
      retained strong cellular immunity, as indicated by high levels of mucosal homing
      and degranulation markers on IFN-gamma+ antigen-specific T cells. A principal
      component analysis distinguished 3 distinct clusters of individuals. The first
      group comprised vaccinated and mildly ill subjects, while clusters 2 and 3
      included mainly infected individuals. Each cluster had immune memory profiles
      that differed in magnitude and quality. These data provide evidence that there
      are substantial similarities between the antiinfluenza response that mildly ill
      and vaccinated individuals develop and that this immune memory signature is
      different from that seen in severely ill individuals.

PMID- 24911150
TI  - Hypomorphic PCNA mutation underlies a human DNA repair disorder.
AB  - Numerous human disorders, including Cockayne syndrome, UV-sensitive syndrome,
      xeroderma pigmentosum, and trichothiodystrophy, result from the mutation of genes
      encoding molecules important for nucleotide excision repair. Here, we describe a
      syndrome in which the cardinal clinical features include short stature, hearing
      loss, premature aging, telangiectasia, neurodegeneration, and photosensitivity,
      resulting from a homozygous missense (p.Ser228Ile) sequence alteration of the
      proliferating cell nuclear antigen (PCNA). PCNA is a highly conserved sliding
      clamp protein essential for DNA replication and repair. Due to this fundamental
      role, mutations in PCNA that profoundly impair protein function would be
      incompatible with life. Interestingly, while the p.Ser228Ile alteration appeared
      to have no effect on protein levels or DNA replication, patient cells exhibited
      marked abnormalities in response to UV irradiation, displaying substantial
      reductions in both UV survival and RNA synthesis recovery. The p.Ser228Ile change
      also profoundly altered PCNA's interaction with Flap endonuclease 1 and DNA
      Ligase 1, DNA metabolism enzymes. Together, our findings detail a mutation of
      PCNA in humans associated with a neurodegenerative phenotype, displaying clinical
      and molecular features common to other DNA repair disorders, which we showed to
      be attributable to a hypomorphic amino acid alteration. 

PMID- 24911154
TI  - Sodiation via heterogeneous disproportionation in FeF2 electrodes for sodium-ion
      batteries.
AB  - Sodium-ion batteries utilize various electrode materials derived from lithium
      batteries. However, the different characteristics inherent in sodium may cause
      unexpected cell reactions and battery performance. Thus, identifying the reactive
      discrepancy between sodiation and lithiation is essential for fundamental
      understanding and practical engineering of battery materials. Here we reveal a
      heterogeneous sodiation mechanism of iron fluoride (FeF2) nanoparticle electrodes
      by combining in situ/ex situ microscopy and spectroscopy techniques. In contrast
      to direct one-step conversion reaction with lithium, the sodiation of FeF2
      proceeds via a regular conversion on the surface and a disproportionation
      reaction in the core, generating a composite structure of 1-4 nm ultrafine Fe
      nanocrystallites (further fused into conductive frameworks) mixed with an
      unexpected Na3FeF6 phase and a NaF phase in the shell. These findings demonstrate
      a core-shell reaction mode of the sodiation process and shed light on the
      mechanistic understanding extended to generic electrode materials for both Li-
      and Na-ion batteries. 

PMID- 24911153
TI  - Fumarate analogs act as allosteric inhibitors of the human mitochondrial NAD(P)+
      dependent malic enzyme.
AB  - Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is
      allosterically activated by the four-carbon trans dicarboxylic acid, fumarate.
      Previous studies have suggested that the dicarboxylic acid in a trans
      conformation around the carbon-carbon double bond is required for the allosteric
      activation of the enzyme. In this paper, the allosteric effects of fumarate
      analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m
      NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME,
      were used as the negative controls. Among these analogs, mesaconate, trans
      aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators
      of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate
      were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for
      diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the
      allosteric inhibitors may impede the conformational change from open form to
      closed form and therefore inhibit m-NAD(P)-ME enzyme activity. 

PMID- 24911151
TI  - Immune activation alters cellular and humoral responses to yellow fever 17D
      vaccine.
AB  - BACKGROUND: Defining the parameters that modulate vaccine responses in African
      populations will be imperative to design effective vaccines for protection
      against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed
      to evaluate the contribution of the patient-specific immune microenvironment to
      the response to the licensed yellow fever vaccine 17D (YF-17D) in an African
      cohort. METHODS: We compared responses to YF-17D in 50 volunteers in Entebbe,
      Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell
      and B cell responses induced by YF-17D and correlated them with immune parameters
      analyzed by flow cytometry prior to vaccination. RESULTS: We showed that YF-17D
      induced CD8+ T cell and B cell responses were substantially lower in immunized
      individuals from Entebbe compared with immunized individuals from Lausanne. The
      impaired vaccine response in the Entebbe cohort associated with reduced YF-17D
      replication. Prior to vaccination, we observed higher frequencies of exhausted
      and activated NK cells, differentiated T and B cell subsets and proinflammatory
      monocytes, suggesting an activated immune microenvironment in the Entebbe
      volunteers. Interestingly, activation of CD8+ T cells and B cells as well as
      proinflammatory monocytes at baseline negatively correlated with YF-17D
      neutralizing antibody titers after vaccination. Additionally, memory T and B cell
      responses in preimmunized volunteers exhibited reduced persistence in the Entebbe
      cohort but were boosted by a second vaccination. CONCLUSION: Together, these
      results demonstrate that an activated immune microenvironment prior to
      vaccination impedes efficacy of the YF-17D vaccine in an African cohort and
      suggest that vaccine regimens may need to be boosted in African populations to
      achieve efficient immunity. TRIAL REGISTRATION: Registration is not required for
      observational studies. FUNDING: This study was funded by Canada's Global Health
      Research Initiative, Defense Threat Reduction Agency, National Institute of
      Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United
      States Agency for International Development.

PMID- 24911155
TI  - Motor phenotype of decline in cognitive performance among community-dwellers
      without dementia: population-based study and meta-analysis.
AB  - BACKGROUND: Decline in cognitive performance is associated with gait
      deterioration. Our objectives were: 1) to determine, from an original study in
      older community-dwellers without diagnosis of dementia, which gait parameters,
      among slower gait speed, higher stride time variability (STV) and Timed Up & Go
      test (TUG) delta time, were most strongly associated with lower performance in
      two cognitive domains (i.e., episodic memory and executive function); and 2) to
      quantitatively synthesize, with a systematic review and meta-analysis, the
      association between gait performance and cognitive decline (i.e., mild cognitive
      impairment (MCI) and dementia). METHODS: Based on a cross-sectional design, 934
      older community-dwellers without dementia (mean+/-standard deviation, 70.3+/
      4.9years; 52.1% female) were recruited. A score at 5 on the Short Mini-Mental
      State Examination defined low episodic memory performance. Low executive
      performance was defined by clock-drawing test errors. STV and gait speed were
      measured using GAITRite system. TUG delta time was calculated as the difference
      between the times needed to perform and to imagine the TUG. Then, a systematic
      Medline search was conducted in November 2013 using the Medical Subject Heading
      terms "Delirium," "Dementia," "Amnestic," "Cognitive disorders" combined with
      "Gait" OR "Gait disorders, Neurologic" and "Variability." FINDINGS: A total of
      294 (31.5%) participants presented decline in cognitive performance. Higher STV,
      higher TUG delta time, and slower gait speed were associated with decline in
      episodic memory and executive performances (all P-values <0.001). The highest
      magnitude of association was found for higher STV (effect size  =  -0.74 [95%
      Confidence Interval (CI): -1.05;-0.43], among participants combining of decline
      in episodic memory and in executive performances). Meta-analysis underscored that
      higher STV represented a gait biomarker in patients with MCI (effect size  = 
      0.48 [95% CI: 0.30;0.65]) and dementia (effect size  = 1.06 [95% CI: 0.40;1.72]).
      CONCLUSION: Higher STV appears to be a motor phenotype of cognitive decline.

PMID- 24911156
TI  - Effects of grain shape on packing and dilatancy of sheared granular materials.
AB  - A granular material exposed to shear shows a variety of unique phenomena:
      Reynolds dilatancy, positional order and orientational order effects may compete
      in the shear zone. We study granular packing consisting of macroscopic prolate,
      oblate and spherical grains and compare their behaviour. X-ray tomography is used
      to determine the particle positions and orientations in a cylindrical split
      bottom shear cell. Packing densities and the arrangements of individual particles
      in the shear zone are evaluated. For anisometric particles, we observe the
      competition of two opposite effects. On the one hand, the sheared granules are
      dilated, on the other hand the particles reorient and align with respect to the
      streamlines. Even though aligned cylinders in principle may achieve higher
      packing densities, this alignment compensates for the effect of dilatancy only
      partially. The complex rearrangements lead to a depression of the surface above
      the well oriented region while neighbouring parts still show the effect of
      dilation in the form of heaps. For grains with isotropic shapes, the surface
      remains rather flat. Perfect monodisperse spheres crystallize in the shear zone,
      whereby positional order partially overcompensates dilatancy effects. However,
      even slight deviations from the ideal monodisperse sphere shape inhibit
      crystallization. 

PMID- 24911152
TI  - Missense dopamine transporter mutations associate with adult parkinsonism and
      ADHD.
AB  - Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread
      brain disorders that involve disturbances of dopaminergic signaling. The sodium
      coupled dopamine transporter (DAT) controls dopamine homeostasis, but its
      contribution to disease remains poorly understood. Here, we analyzed a cohort of
      patients with atypical movement disorder and identified 2 DAT coding variants,
      DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with
      early-onset parkinsonism and ADHD. According to DAT single-photon emission
      computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG
      PET/MRI) scan, the patient suffered from progressive dopaminergic
      neurodegeneration. In heterologous cells, both DAT variants exhibited markedly
      reduced dopamine uptake capacity but preserved membrane targeting, consistent
      with impaired catalytic activity. Computational simulations and uptake
      experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is
      the result of compromised sodium binding, in agreement with Asp421 coordinating
      sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments
      revealed a constitutive, anomalous efflux of dopamine, and electrophysiological
      analyses identified a large cation leak that might further perturb dopaminergic
      neurotransmission. Our results link specific DAT missense mutations to
      neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric
      comorbidity provides additional support for the idea that DAT missense mutations
      are an ADHD risk factor and suggests that complex DAT genotype and phenotype
      correlations contribute to different dopaminergic pathologies. 

PMID- 24911157
TI  - Influencing factors of new-onset diabetes after a renal transplant and their
      effects on complications and survival rate.
AB  - OBJECTIVE: To discuss the onset of and relevant risk factors for new-onset
      diabetes after a transplant (NODAT) in patients who survive more than 1 year
      after undergoing a renal transplant and the influence of these risk factors on
      complications and long-term survival. METHOD: A total of 428 patients who
      underwent a renal transplant between January 1993 and December 2008 and were not
      diabetic before surgery were studied. The prevalence rate of and relevant risk
      factors for postoperative NODAT were analyzed on the basis of fasting plasma
      glucose (FPG) levels, and differences in postoperative complications and survival
      rates between patients with and without NODAT were compared. RESULTS: The
      patients in this study were followed up for a mean of 5.65 +/- 3.68 years. In
      total, 87 patients (20.3%) developed NODAT. Patients who converted from treatment
      with CSA to FK506 had increased prevalence rates of NODAT (P <0.05). Multi-factor
      analysis indicated that preoperative FPG level (odds ratio [OR]  =  1.48), age
      (OR  =  1.10), body mass index (OR  =  1.05), hepatitis C virus infection (OR  = 
      2.72), and cadaveric donor kidney (OR  =  1.18) were independent risk factors for
      NODAT (All P <0.05). Compared with the N-NODAT group, the NODAT group had higher
      prevalence rates (P < 0.05) of postoperative infection, hypertension, and
      dyslipidemia; in addition, the survival rate and survival time of the 2 groups
      did not significantly differ. CONCLUSION: Among the patients who survived more
      than 1 year after a renal transplant, the prevalence rate of NODAT was 20.32%.
      Preoperative FPG level, age, body mass index, hepatitis C virus infection, and
      cadaveric donor kidney were independent risk factors for NODAT. Patients who
      converted from treatment with CSA to FK506 after a renal transplant had
      aggravated impairments in glycometabolism. Patients with NODAT were also more
      vulnerable to postoperative complications such as infection, hypertension, and
      hyperlipidemia.

PMID- 24911158
TI  - Soft propargylic deprotonation: designed ligand enables Au-catalyzed
      isomerization of alkynes to 1,3-dienes.
AB  - By functionalizing the privileged biphenyl-2-ylphosphine with a basic amino group
      at the rarely explored 3' position, the derived gold(I) complex possesses
      orthogonally positioned "push" and "pull" forces, which enable for the first time
      soft propargylic deprotonation and permit the bridging of a difference of >26
      pK(a) units (in DMSO) between a propargylic hydrogen and a protonated tertiary
      aniline. The application of this design led to efficient isomerization of alkynes
      into versatile 1,3-dienes with synthetically useful scope under mild reaction
      conditions.

PMID- 24911159
TI  - Redox modulation of FAK controls melanoma survival--role of NOX4.
AB  - Studies have demonstrated that reactive oxygen species (ROS) generated by NADPH
      oxidase are essential for melanoma proliferation and survival. However, the
      mechanisms by which NADPH oxidase regulates these effects are still unclear. In
      this work, we investigate the role of NADPH oxidase-derived ROS in the signaling
      events that coordinate melanoma cell survival. Using the highly metastatic human
      melanoma cell line MV3, we observed that pharmacological NADPH oxidase inhibition
      reduced melanoma viability and induced dramatic cellular shape changes. These
      effects were accompanied by actin cytoskeleton rearrangement, diminished FAKY397
      phosphorylation, and decrease of FAK-actin and FAK-cSrc association, indicating
      disassembly of focal adhesion processes, a phenomenon that often results in
      anoikis. Accordingly, NADPH oxidase inhibition also enhanced hypodiploid DNA
      content, and caspase-3 activation, suggesting activation of the apoptotic
      machinery. NOX4 is likely to be involved in these effects, since silencing of
      NOX4 significantly inhibited basal ROS production, reduced FAKY397
      phosphorylation and decreased tumor cell viability. Altogether, the results
      suggest that intracellular ROS generated by the NADPH oxidase, most likely NOX4,
      transmits cell survival signals on melanoma cells through the FAK pathway,
      maintaining adhesion contacts and cell viability. 

PMID- 24911160
TI  - Sex differences in wild chimpanzee behavior emerge during infancy.
AB  - The role of biological and social influences on sex differences in human child
      development is a persistent topic of discussion and debate. Given their many
      similarities to humans, chimpanzees are an important study species for
      understanding the biological and evolutionary roots of sex differences in human
      development. In this study, we present the most detailed analyses of wild
      chimpanzee infant development to date, encompassing data from 40 infants from the
      long-term study of chimpanzees at Gombe National Park, Tanzania. Our goal was to
      characterize age-related changes, from birth to five years of age, in the percent
      of observation time spent performing behaviors that represent important
      benchmarks in nutritional, motor, and social development, and to determine
      whether and in which behaviors sex differences occur. Sex differences were found
      for indicators of social behavior, motor development and spatial independence
      with males being more physically precocious and peaking in play earlier than
      females. These results demonstrate early sex differentiation that may reflect
      adult reproductive strategies. Our findings also resemble those found in humans,
      which suggests that biologically-based sex differences may have been present in
      the common ancestor and operated independently from the influences of modern sex
      biased parental behavior and gender socialization. 

PMID- 24911161
TI  - Delayed fracture healing and increased callus adiposity in a C57BL/6J murine
      model of obesity-associated type 2 diabetes mellitus.
AB  - INTRODUCTION: Impaired healing and non-union of skeletal fractures is a major
      public health problem, with morbidity exacerbated in patients with diabetes
      mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million
      US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture
      healing in type 1 DM (T1DM) has been studied using animal models, an
      investigation into delayed healing in an animal model of T2DM has not yet been
      performed. METHODS: Male C57BL/6J mice at 5 weeks of age were placed on either a
      control lean diet or an experimental high-fat diet (HFD) for 12 weeks. A mid
      diaphyseal open tibia fracture was induced at 17 weeks of age and a spinal needle
      was used for intra-medullary fixation. Mice were sacrificed at days 7, 10, 14,
      21, 28, and 35 for micro-computed tomography (MUCT), histology-based
      histomorphometry and molecular analyses, and biomechanical testing. RESULTS: HFD
      fed mice displayed increased body weight and impaired glucose tolerance, both
      characteristic of T2DM. Compared to control mice, HFD-fed mice with tibia
      fractures showed significantly (p<0.001) decreased woven bone at day 28 by
      histomorphometry and significantly (p<0.01) decreased callus bone volume at day
      21 by MUCT. Interestingly, fracture calluses contained markedly increased
      adiposity in HFD-fed mice at days 21, 28, and 35. HFD-fed mice also showed
      increased PPARgamma immunohistochemical staining at day 14. Finally, calluses
      from HFD-fed mice at day 35 showed significantly (p<0.01) reduced torsional
      rigidity compared to controls. DISCUSSION: Our murine model of T2DM demonstrated
      delayed fracture healing and weakened biomechanical properties, and was
      distinctly characterized by increased callus adiposity. This suggests altered
      mesenchymal stem cell fate determination with a shift to the adipocyte lineage at
      the expense of the osteoblast lineage. The up-regulation of PPARgamma in fracture
      calluses of HFD-fed mice is likely involved in the proposed fate switching.

PMID- 24911163
TI  - Survey of external cephalic version services in the East of England region:
      comparison of services in 2007 and 2012.
AB  - External cephalic version (ECV) has been recognised by the Royal college of
      Obstetricians and Gynaecologists (RCOG) as a safe procedure for the conversion of
      breech presentations to cephalic presentation. The need to reduce the incidence
      of breech presentations is due to the associated increase in complications for
      both mother and baby in a breech delivery. The RCOG published the Green-top
      Guideline No. 20a in December 2006 and revised it in December 2010. In our study,
      we conducted a survey across all hospitals in the East of England (EoE) region in
      2007 and 2012 to assess the ECV service and to determine if this fulfils the RCOG
      recommendations.

PMID- 24911162
TI  - Cortical bone mechanical properties are altered in an animal model of progressive
      chronic kidney disease.
AB  - Chronic kidney disease (CKD), which leads tocortical bone loss and
      increasedporosity,increases therisk of fracture. Animal models have confirmed
      that these changes compromise whole bone mechanical properties. Estimates from
      whole bone testing suggest that material properties are negatively affected,
      though tissue-level assessmentshavenot been conducted. Therefore, the goal of the
      present study was to examine changes in cortical bone at different length scales
      using a rat model with theprogressive development of CKD. At 30 weeks of age
      (~75% reduction in kidney function), skeletally mature male Cy/+ rats were
      compared to their normal littermates. Cortical bone material propertieswere
      assessed with reference point indentation (RPI), atomic force microscopy (AFM),
      Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from
      animals with CKD had higher (+18%) indentation distance increase and first cycle
      energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader
      distribution of elastic modulus values in CKD animals witha greater proportion of
      both higher and lower modulus values compared to normal controls. Yet, tissue
      composition, collagen morphology, and collagen cross-linking fail to account for
      these differences. Though the specific skeletal tissue alterations responsible
      for these mechanical differences remain unclear, these results indicate that
      cortical bone material properties are altered in these animals and may contribute
      to the increased fracture risk associated with CKD. 

PMID- 24911164
TI  - Non-word repetition: the relationship between weak syllables and the omission of
      grammatical morphemes in children with specific language impairment.
AB  - Non-word (NW) repetition in children with specific language impairment (SLI) is a
      skill related to, but genetically separate from, grammatical ability. Prosodic
      structure of the syllables may bridge the gap between these two abilities. A NW
      repetition task was compared in a group of 15 preschool Italian children with SLI
      (ranged in age from 3;11 to 5;8) and 15 younger typically developing children
      (aged from 2;11 to 3;7) matched for mean length of utterance (TD-MLU).
      Grammatical ability was tested through a probe for direct-object clitic pronouns
      which is one of the most useful clinical markers in the Italian language. In NW
      repetition, children with SLI deleted more syllables than the TD-MLU children.
      The omission of weak syllables in a pre-stress position was a significant
      predictor of the omission of clitic pronouns. The present study shows that the
      link between grammar and NW is due to a prosodic characteristic that is more
      universally challenging in children with SLI.

PMID- 24911165
TI  - Rapid, low-cost and instrument-free CD4+ cell counting for HIV diagnostics in
      resource-poor settings.
AB  - We present a novel, user-friendly and widely autonomous point-of-care diagnostic
      to enable HIV monitoring in resource-poor regions where the current pandemic is
      most prevalent. To specifically isolate magnetically tagged CD4+ cells directly
      from patient blood, the low-cost and disposable microfluidic chip operates by
      dual-force CD4+ cell magnetophoresis; whereby the interplay of flow and magnetic
      fields governs the trajectory of target cells depending on whether the cell binds
      to a magnetic microbead. Instrument-free pumping is implemented by a finger
      actuated elastic membrane; tagged beads are laterally deflected by a small and re
      useable permanent magnet. The single-depth and monolithic microfluidic structure
      can easily be fabricated in a single casting step. After their magnetophoretic
      isolation from whole blood, estimation of CD4+ cell concentrations is then
      measured by bright-field inspection of the capture chamber. In addition, an
      optional fluorescence measurement can be used for confirmation of the bright
      field result if required. On-chip CD4+ estimation produces a linear response over
      the full range of medically relevant CD4+ cell concentrations. Our technology
      combines high-efficiency capture (93.0 +/- 3.3%) and cell enumeration. 

PMID- 24911166
TI  - Identification and characterization of a ginsenoside-transforming beta
      glucosidase from Pseudonocardia sp. Gsoil 1536 and its application for enhanced
      production of minor ginsenoside Rg2(S).
AB  - The ginsenoside Rg2(S), which is one of the pharmaceutical components of ginseng,
      is known to have neuroprotective, anti-inflammation, and anti-diabetic effects.
      However, the usage of ginsenoside Rg2(S) is restricted owing to the small amounts
      found in white and red ginseng. To enhance the production of ginsenoside Rg2(S)
      as a 100 gram unit with high specificity, yield, and purity, an enzymatic
      bioconversion method was developed to adopt the recombinant glycoside hydrolase
      (BglPC28), which is a ginsenoside-transforming recombinant beta-glucosidase from
      Pseudonocardia sp. strain Gsoil 1536. The gene, termed bglPC28, encoding beta
      glucosidase (BglPC28) belonging to the glycoside hydrolase family 3 was cloned.
      bglPC28 consists of 2,232 bp (743 amino acid residues) with a predicted molecular
      mass of 78,975 Da. This enzyme was overexpressed in Escherichia coli BL21(DE3)
      using a GST-fused pGEX 4T-1 vector system. The optimum conditions of the
      recombinant BglPC28 were pH 7.0 and 37  degrees C. BglPC28 can effectively
      transform the ginsenoside Re to Rg2(S); the Km values of PNPG and Re were 6.36 +/
      1.10 and 1.42 +/- 0.13 mM, respectively, and the Vmax values were 40.0 +/- 2.55
      and 5.62 +/- 0.21 umol min-1 mg-1 of protein, respectively. A scaled-up
      biotransformation reaction was performed in a 10 L jar fermenter at pH 7.0 and 30
      degrees C for 12 hours with a concentration of 20 mg/ml of ginsenoside Re from
      American ginseng roots. Finally, 113 g of Rg2(S) was produced from 150 g of Re
      with 84.0 +/- 1.1% chromatographic purity. These results suggest that this
      enzymatic method could be usefully exploited in the preparation of ginsenoside
      Rg2(S) in the cosmetics, functional food, and pharmaceutical industries.

PMID- 24911167
TI  - Detection of amyloid-beta42 using a waveguide-coupled bimetallic surface plasmon
      resonance sensor chip in the intensity measurement mode.
AB  - The waveguide-coupled bimetallic (WcBiM) surface plasmon resonance (SPR) chip had
      been utilized in the intensity interrogation detection mode to detect amyloid
      beta42 (Abeta42), a biomarker of the Alzheimer disease. The SPR reflectance curve
      of the WcBiM chip has the narrower full-width-at-half-maximum (FWHM) compared
      with the SPR reflectance curve of the conventional gold (Au) chip, resulting in
      the steeper gradient. For the enhancement of resolution, the light source was
      fixed at an angle where the slope of the reflectance curve is the steepest, and
      the change in the reflectance was monitored. For the detection of Abeta42, the
      antibody of Abeta42 (anti-Abeta42) was immobilized on the WcBiM SPR chip using
      the self-assembled monolayer. The SPR responses, the average changes in the
      reflectance to the Abeta42 at the concentrations of 100 pg/ml, 250 pg/ml, 500
      pg/ml, 750 pg/ml, 1,000 pg/ml, and 2,000 pg/ml were 0.0111%, 0.0305%, 0.0867%,
      0.1712%, 0.3021%, and 0.5577%, respectively, for the three replicates. From
      linear regression analysis, the calibration curve indicated that the SPR response
      had a linear relation with Abeta42 with the concentration in the range of 100
      pg/ml to 2,000 pg/ml. A control experiment showed the anti-Abeta42-modified
      surface of the WcBiM chip had a high specificity to Abeta42. Thus, the enhanced
      resolution by utilizing the WcBiM SPR chip in the intensity interrogation
      detection mode aids the diagnosis of the Alzheimer disease by detecting the
      Abeta42 around the criteria concentration (500 pg/ml) without any labeling. 

PMID- 24911168
TI  - A spatial and temporal analysis of Japanese encephalitis in mainland China, 1963
      1975: a period without Japanese encephalitis vaccination.
AB  - More than a million Japanese encephalitis (JE) cases occurred in mainland China
      from the 1960s to 1970s without vaccine interventions. The aim of this study is
      to analyze the spatial and temporal pattern of JE cases reported in mainland
      China from 1965 to 1973 in the absence of JE vaccination, and to discuss the
      impacts of climatic and geographical factors on JE during that period. Thus, the
      data of reported JE cases at provincial level and monthly precipitation and
      monthly mean temperature from 1963 to 1975 in mainland China were collected.
      Local Indicators of Spatial Association analysis was performed to identify
      spatial clusters at the province level. During that period, The epidemic peaked
      in 1966 and 1971 and the JE incidence reached up to 20.58/100000 and
      20.92/100000, respectively. The endemic regions can be divided into three classes
      including high, medium, and low prevalence regions. Through spatial cluster
      analysis, JE epidemic hot spots were identified; most were located in the Yangtze
      River Plain which lies in the southeast of China. In addition, JE incidence was
      shown to vary among eight geomorphic units in China. Also, the JE incidence in
      the Loess Plateau and the North China Plain was showed to increase with the rise
      of temperature. Likewise, JE incidence in the Loess Plateau and the Yangtze River
      Plain was observed a same trend with the increase of rainfall. In conclusion, the
      JE cases clustered geographically during the epidemic period. Besides, the JE
      incidence was markedly higher on the plains than plateaus. These results may
      provide an insight into the epidemiological characteristics of JE in the absence
      of vaccine interventions and assist health authorities, both in China and
      potentially in Europe and Americas, in JE prevention and control strategies. 

PMID- 24911169
TI  - Genome-wide mapping of virulence in brown planthopper identifies loci that break
      down host plant resistance.
AB  - Insects and plants have coexisted for over 350 million years and their
      interactions have affected ecosystems and agricultural practices worldwide.
      Variation in herbivorous insects' virulence to circumvent host resistance has
      been extensively documented. However, despite decades of investigation, the
      genetic foundations of virulence are currently unknown. The brown planthopper
      (Nilaparvata lugens) is the most destructive rice (Oryza sativa) pest in the
      world. The identification of the resistance gene Bph1 and its introduction in
      commercial rice varieties prompted the emergence of a new virulent brown
      planthopper biotype that was able to break the resistance conferred by Bph1. In
      this study, we aimed to construct a high density linkage map for the brown
      planthopper and identify the loci responsible for its virulence in order to
      determine their genetic architecture. Based on genotyping data for hundreds of
      molecular markers in three mapping populations, we constructed the most
      comprehensive linkage map available for this species, covering 96.6% of its
      genome. Fifteen chromosomes were anchored with 124 gene-specific markers. Using
      genome-wide scanning and interval mapping, the Qhp7 locus that governs preference
      for Bph1 plants was mapped to a 0.1 cM region of chromosome 7. In addition, two
      major QTLs that govern the rate of insect growth on resistant rice plants were
      identified on chromosomes 5 (Qgr5) and 14 (Qgr14). This is the first study to
      successfully locate virulence in the genome of this important agricultural insect
      by marker-based genetic mapping. Our results show that the virulence which
      overcomes the resistance conferred by Bph1 is controlled by a few major genes and
      that the components of virulence originate from independent genetic characters.
      The isolation of these loci will enable the elucidation of the molecular
      mechanisms underpinning the rice-brown planthopper interaction and facilitate the
      development of durable approaches for controlling this most destructive
      agricultural insect. 

PMID- 24911170
TI  - Bistability in glycolysis pathway as a physiological switch in energy metabolism.
AB  - The flux of glycolysis is tightly controlled by feed-back and feed-forward
      allosteric regulations to maintain the body's glucose homeostasis and to respond
      to cell's growth and energetic needs. Using a mathematical model based on
      reported mechanisms for the allosteric regulations of the enzymes, we demonstrate
      that glycolysis exhibits multiple steady state behavior segregating glucose
      metabolism into high flux and low flux states. Two regulatory loops centering on
      phosphofructokinase and on pyruvate kinase each gives rise to the bistable
      behavior, and together impose more complex flux control. Steady state
      multiplicity endows glycolysis with a robust switch to transit between the two
      flux states. Under physiological glucose concentrations the glycolysis flux does
      not move between the states easily without an external stimulus such as hormonal,
      signaling or oncogenic cues. Distinct combination of isozymes in glycolysis gives
      different cell types the versatility in their response to different biosynthetic
      and energetic needs. Insights from the switch behavior of glycolysis may reveal
      new means of metabolic intervention in the treatment of cancer and other
      metabolic disorders through suppression of glycolysis. 

PMID- 24911171
TI  - Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit
      in Alzheimer's disease rat model.
AB  - In this study, we aim to demonstrate the fate of allogenic adult human olfactory
      bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat
      hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to
      hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed
      their possible ability to survive, integrate, proliferate, and differentiate into
      different neuronal and glial elements: we also evaluate their possible
      therapeutic potential, and the mechanism(s) relevant to neuroprotection following
      their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human
      olfactory bulb patients, genetically engineered to express GFP and human nerve
      growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically
      transplanted into the hippocampus of IBO-treated animals and controls.
      Stereological analysis of engrafted OBNSCs eight weeks post transplantation
      revealed a 1.89 fold increase with respect to the initial cell population,
      indicating a marked ability for survival and proliferation. In addition, 54.71 +/
      11.38%, 30.18 +/- 6.00%, and 15.09 +/- 5.38% of engrafted OBNSCs were identified
      by morphological criteria suggestive of mature neurons, oligodendrocytes and
      astrocytes respectively. Taken together, this work demonstrated that human OBNSCs
      expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced
      lesions in AD model rats, and the improvement can probably be attributed
      primarily to neuronal and glial cell replacement as well as the trophic influence
      exerted by the secreted NGF.

PMID- 24911172
TI  - Risk factors for rebleeding of aneurysmal subarachnoid hemorrhage: a meta
      analysis.
AB  - BACKGROUND: Rebleeding is a serious complication of aneurysmal subarachnoid
      hemorrhaging. To date, there are conflicting data regarding the factors
      contributing to rebleeding and their significance. METHODS: A systematic review
      of PubMed and Embase databases was conducted for studies pertaining to aneurysmal
      subarachnoid hemorrhage (aSAH) and rebleeding in order to assess the associated
      risk factors. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs)
      were estimated from fourteen studies comprised of a total of 5693 patients that
      met the inclusion criteria. RESULTS: Higher rebleeding rates were observed < 6 h
      after the initial aSAH (OR  = 3.22, 95% CI  = 1.46-7.12), and were associated
      with high systolic blood pressure (OR  = 1.93, 95% CI  = 1.31-2.83), poor Hunt
      Hess grade (III-IV) (OR  = 3.43, 95% CI  = 2.33-5.05), intracerebral or
      intraventricular hematomas (OR  = 1.65, 95% CI  = 1.33-2.05), posterior
      circulation aneurysms (OR  = 2.15, 95% CI  = 1.32-3.49), and aneurysms >10 mm in
      size (OR  = 1.70, 95% CI  = 1.35-2.14). CONCLUSIONS: Aneurysmal rebleeding occurs
      more frequently within the first 6 hours after the initial aSAH. Risk factors
      associated with rebleeding include high systolic pressure, the presence of an
      intracerebral or intraventricular hematoma, poor Hunt-Hess grade (III-IV),
      aneurysms in the posterior circulation, and an aneurysm >10 mm in size.

PMID- 24911173
TI  - Aerobic Exercise Reduces Symptoms of Posttraumatic Stress Disorder: A Randomized
      Controlled Trial.
AB  - Evidence suggests aerobic exercise has anxiolytic effects; yet, the treatment
      potential for posttraumatic stress disorder (PTSD) and responsible anxiolytic
      mechanisms have received little attention. Emerging evidence indicates that
      attentional focus during exercise may dictate the extent of therapeutic benefit.
      Whether benefits are a function of attentional focus toward or away from somatic
      arousal during exercise remains untested. Thirty-three PTSD-affected participants
      completed two weeks of stationary biking aerobic exercise (six sessions). To
      assess the effect of attentional focus, participants were randomized into three
      exercise groups: group 1 (attention to somatic arousal) received prompts
      directing their attention to the interoceptive effects of exercise, group 2
      (distraction from somatic arousal) watched a nature documentary, and group 3
      exercised with no distractions or interoceptive prompts. Hierarchal linear
      modeling showed all groups reported reduced PTSD and anxiety sensitivity (AS;
      i.e., fear of arousal-related somatic sensations) during treatment. Interaction
      effects between group and time were found for PTSD hyperarousal and AS physical
      and social scores, wherein group 1, receiving interoceptive prompts, experienced
      significantly less symptom reduction than other groups. Most participants (89%)
      reported clinically significant reductions in PTSD severity after the two-week
      intervention. Findings suggest, regardless of attentional focus, aerobic exercise
      reduces PTSD symptoms. 

PMID- 24911174
TI  - Anxiety, depression and school absenteeism in youth with chronic or episodic
      headache.
AB  - BACKGROUND: Chronic daily headache (CDH) in children has been documented in
      general and clinical populations. Comorbid psychological conditions, risk factors
      and functional outcomes of CDH in children are not well understood. OBJECTIVES:
      To examine anxiety and depression, associated risk factors and school outcomes in
      a clinical population of youth with CDH compared with youth with episodic
      headache (EH). METHODS: Data regarding headache characteristics, anxiety,
      depression and missed school days were collected from 368 consecutive patients
      eight to 17 years of age, who presented with primary headache at a specialized
      pediatric headache centre. RESULTS: A total of 297 patients (81%) were diagnosed
      with EH and 71 were diagnosed with CDH. Among those with CDH, 78.9% presented
      with chronic tension-type headache and 21.1% with chronic migraine (CM). Children
      with CDH had a higher depression score than the standardized reference
      population. No difference was observed for anxiety or depression scores between
      children with CDH and those with EH. However, children with CM were more anxious
      and more depressed than those with chronic tension-type headache. Youth
      experiencing migraine with aura were three times as likely to have clinically
      significant anxiety scores. Headache frequency and history were not associated
      with psychopathological symptoms. Children with CDH missed school more often and
      for longer periods of time. CONCLUSIONS: These findings document the prevalence
      of anxiety, depression and school absenteeism in youth with CDH or EH. The
      present research also extends recent studies examining the impact of aura on
      psychiatric comorbidity and the debate on CM criteria.

PMID- 24911175
TI  - Exposure to virtual social stimuli modulates subjective pain reports.
AB  - BACKGROUND: Contextual factors, including the gender of researchers, influence
      experimental and patient pain reports. It is currently not known how social
      stimuli influence pain percepts, nor which types of sensory modalities of
      communication, such as auditory, visual or olfactory cues associated with person
      perception and gender processing, produce these effects. OBJECTIVES: To determine
      whether exposure to two forms of social stimuli (audio and visual) from a virtual
      male or female stranger modulates cold pressor task (CPT) pain reports. METHODS:
      Participants with similar demographic characteristics conducted a CPT in
      solitude, without the physical presence of an experimenter or another person.
      During the CPT, participants were exposed to the voice and image of a virtual
      male or female stranger. The voices had analogous vocal prosody, provided no
      semantic information (spoken in a foreign language) and differed only in pitch;
      the images depicted a middle-age male or female health care practitioner.
      RESULTS: Male participants, but not females, showed higher CPT pain intensity
      when they were exposed to the female stimuli compared with the male stimuli.
      Follow-up analyses showed that the association between the social stimuli and
      variability in pain sensitivity was not moderated by individual differences in
      subjective (eg, self-image) or objective measurements of one's physical stature.
      DISCUSSION: The findings show that exposure to virtual, gender-based auditory and
      visual social stimuli influences exogenous pain sensitivity. CONCLUSION: Further
      research on how contextual factors, such as the vocal properties of health care
      examiners and exposure to background voices, may influence momentary pain
      perception is necessary for creating more standardized methods for measuring
      patient pain reports in clinical settings.

PMID- 24911176
TI  - The relationship between pain and eating among overweight and obese individuals
      with osteoarthritis: an ecological momentary study.
AB  - BACKGROUND: Osteoarthritis (OA) patients who are overweight or obese report
      higher levels of pain compared with their normal-weight OA counterparts. Evidence
      suggests that overweight or obese OA patients also experience pain relief from
      eating foods high in calories, fat or sugar. Eating to alleviate pain may be
      problematic because it can lead to additional weight gain, which may contribute
      to heightened pain. OBJECTIVES: To investigate the relationship between pain and
      food intake using ecological momentary assessments in a sample of 71 overweight
      and obese OA patients. METHODS: Participants completed two consecutive days of
      diary entries in which they recorded their levels of pain, mood and food intake
      throughout the day. Data were analyzed using generalized estimating equations
      that modelled pain as a predictor of calorie, fat and sugar intake. All models
      were adjusted for sex, body mass index, negative mood, time and treatment
      history. RESULTS: Pain significantly predicted calorie (Z=2.57; P=0.01) and fat
      intake (Z=1.99; P=0.05). CONCLUSIONS: Using ecological momentary assessments as a
      novel approach, the present study provides preliminary data supporting a
      relationship between pain and food intake among overweight and obese OA patients.
      Continued advances in our understanding of the relationship between pain and
      eating behaviour may help to optimize intervention strategies for these patients.

PMID- 24911177
TI  - When in doubt, ask the audience: potential users' perceptions of Internet
      delivered cognitive behavioural therapy for chronic pain.
AB  - BACKGROUND: Although research has demonstrated that Internet-delivered cognitive
      behavioural therapy (ICBT) for chronic pain helps with adjustment to pain, it
      remains unclear how this treatment option would initially be perceived by
      individuals with chronic pain. OBJECTIVES: To explore initial perceptions of ICBT
      and to examine variables that correlate with an expressed interest in ICBT as a
      treatment option among individuals with chronic pain. METHODS: A total of 129
      individuals with chronic pain completed a survey assessing perceptions of ICBT
      and individual difference variables that could be correlated with expressed
      interest in ICBT (eg, demographic characteristics, pain, computer self-efficacy).
      RESULTS: Results showed that most participants perceived ICBT as a potentially
      valuable service with multiple benefits. Being female, having greater pain
      severity and interference, and having greater computer self-efficacy and lower
      computer anxiety were positively correlated with interest in receiving ICBT.
      CONCLUSIONS: Combined with previous research on treatment efficacy of ICBT for
      chronic pain, the results should serve to stimulate further research on
      integrating ICBT within existing health care services.

PMID- 24911178
TI  - Morning employees are perceived as better employees: employees' start times
      influence supervisor performance ratings.
AB  - In this research, we draw from the stereotyping literature to suggest that
      supervisor ratings of job performance are affected by employees' start times-the
      time of day they first arrive at work. Even when accounting for total work hours,
      objective job performance, and employees' self-ratings of conscientiousness, we
      find that a later start time leads supervisors to perceive employees as less
      conscientious. These perceptions in turn cause supervisors to rate employees as
      lower performers. In addition, we show that supervisor chronotype acts as a
      boundary condition of the mediated model. Supervisors who prefer eveningness
      (i.e., owls) are less likely to hold negative stereotypes of employees with late
      start times than supervisors who prefer morningness (i.e., larks). Taken
      together, our results suggest that supervisor ratings of job performance are
      susceptible to stereotypic beliefs based on employees' start times. (PsycINFO
      Database Record (c) 2014 APA, all rights reserved). 

PMID- 24911179
TI  - Creative benefits from well-connected leaders: leader social network ties as
      facilitators of employee radical creativity.
AB  - Employee radical creativity critically depends on substantive informational
      resources from others across the wider organization. We propose that the social
      network ties of employees' immediate leaders assume a central role in garnering
      these resources, thereby fostering their employees' radical creativity both
      independent of and interactively with employees' own network ties. Drawing on
      data from 214 employees working in 30 teams of a public technology and
      environmental services organization, we find that team leaders' betweenness
      centrality in the idea network within their teams as well as among their peer
      leaders provides creative benefits beyond employees' own internal and external
      ties. Further, employees' and leaders' ties within and external to the team
      interactively predict employee radical creativity. Implications for theory and
      practice are discussed.

PMID- 24911180
TI  - New water oxidation chemistry of a seven-coordinate ruthenium complex with a
      tetradentate polypyridyl ligand.
AB  - The mononuclear ruthenium(II) complex [Ru](2+) (Ru = Ru(dpp)(pic)2, where dpp is
      the tetradentate 2,9-dipyrid-2'-yl-1,10-phenanthroline ligand and pic is 4
      picoline) reported by Thummel's group (Inorg. Chem. 2008, 47, 1835-1848) that
      contains no water molecule in its primary coordination shell is evaluated as a
      catalyst for water oxidation in artificial photosynthesis. A detailed theoretical
      characterization of the energetics, thermochemistry, and spectroscopic properties
      of intermediates allowed us to interpret new electrochemical and spectroscopic
      experimental data, and propose a mechanism for the water oxidation process that
      involves an unprecedented sequence of seven-coordinate ruthenium complexes as
      intermediates. This analysis provides insights into a mechanism that generates
      four electrons and four protons in the solution and a gas-phase oxygen molecule
      at different pH values. On the basis of the calculations and corroborated
      substantially by experiments, the catalytic cycle goes through [(2)Ru(III)](3+)
      and [(2)Ru(V)(O)](3+) to [(1)Ru(IV)(OOH)](3+) then [(2)Ru(III)(...(3)O2)](3+) at
      pH 0, and through [(3)Ru(IV)(O)](2+), [(2)Ru(V)(O)](3+), and [(1)Ru(IV)(OO)](2+)
      at pH 9 before reaching the same [(2)Ru(III)(...(3)O2)](3+) species, from which
      the liberation of the weakly bound O2 might require an additional oxidation to
      form [(3)Ru(IV)(O)](2+) to initiate further cycles involving all seven-coordinate
      species. 

PMID- 24911181
TI  - Rationally designed polyimides for high-energy density capacitor applications.
AB  - Development of new dielectric materials is of great importance for a wide range
      of applications for modern electronics and electrical power systems. The state-of
      the-art polymer dielectric is a biaxially oriented polypropylene (BOPP) film
      having a maximal energy density of 5 J/cm(3) and a high breakdown field of 700
      MV/m, but with a limited dielectric constant (~2.2) and a reduced breakdown
      strength above 85  degrees C. Great effort has been put into exploring other
      materials to fulfill the demand of continuous miniaturization and improved
      functionality. In this work, a series of polyimides were investigated as
      potential polymer materials for this application. Polyimide with high dielectric
      constants of up to 7.8 that exhibits low dissipation factors (<1%) and high
      energy density around 15 J/cm(3), which is 3 times that of BOPP, was prepared.
      Our syntheses were guided by high-throughput density functional theory
      calculations for rational design in terms of a high dielectric constant and band
      gap. Correlations of experimental and theoretical results through judicious
      variations of polyimide structures allowed for a clear demonstration of the
      relationship between chemical functionalities and dielectric properties. 

PMID- 24911182
TI  - Policy strategies to improve maternal health services delivery and outcomes in
      Anambra State, Nigeria.
AB  - Pregnancy and childbirth present major health risks for Nigerian women. Key
      maternal mortality measures indicate that the risks are high. Despite improvement
      efforts, the country has made insufficient progress in reaching the United
      Nations' millennium development goal of decreasing maternal mortality by 75% by
      2015. The author in this qualitative descriptive study explores the perspectives
      of experienced nurse leaders on policy strategies to improve maternal health in
      Nigeria. In this study, the author suggests that removal of financial barriers to
      access and utilization of health services, spousal and family inclusiveness in
      plan of care, and health systems-related physical and human infrastructural
      improvements constitute critical policy approaches. 

PMID- 24911183
TI  - Evaluation and validation of a method for determining platelet catecholamine in
      patients with obstructive sleep apnea and arterial hypertension.
AB  - BACKGROUND: Measurements of plasma and urinary catecholamine are susceptible to
      confounding factors that influence the results, complicating the interpretation
      of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA)
      and arterial hypertension (HYP) conditions. OBJECTIVE: In this study, we
      validated a test for platelet catecholamine and compared the catecholamine levels
      (adrenaline and noradrenaline) in urine, plasma and platelets in patients with
      OSA and HYP compared with controls. METHODS: In the validation, 30 healthy,
      nonsmoking volunteers who were not currently undergoing treatment or medication
      were selected as the control group. One hundred fifty-four individuals (114 OSA,
      40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep
      Institute and underwent clinical, polysomnographic and laboratory evaluation,
      including the urinary, plasma and platelet levels of adrenaline (AD) and
      noradrenaline (NA). Patients were then allocated to groups according to the
      presence of OSA and/or hypertension. RESULTS: A logistic regression model,
      controlled for age and BMI, showed that urinary AD and urinary NA were risk
      factors in the OSA+HYP group and the HYP group; however, the model showed higher
      levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper
      airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA
      (p = 0.04) and platelet NA (p = 0.05). CONCLUSION: Urinary NA and AD levels were
      significantly associated with the condition of hypertension with and without OSA,
      whereas platelet NA with OSA without comorbidity. These findings suggest that
      platelet catecholamine levels might reflect nocturnal sympathetic activation in
      OSA patients without hypertension.

PMID- 24911184
TI  - Asymmetric organocatalysis combined with metal catalysis: concept, proof of
      concept, and beyond.
AB  - Asymmetric catalysis has been considered to be the most intriguing means for
      building collections of functionalized optically active compounds. In particular,
      metal and organocatalysis have been well established to allow many fundamentally
      different reactions. Metal catalysis has enabled the participation of a much
      broader scope of chemical bonds in organic transformations than are allowed by
      organocatalysis, while organocatalysis permits a broader scope of functional
      groups to undergo a diverse range of enantioselective transformations,
      individually, simultaneously, or sequentially. Theoretically, the combination of
      organocatalysts and metal complexes could probably render new transformations
      through the simultaneous or sequential activation and reorganization of multiple
      chemical bonds if the superior features of both the catalysts are adopted. In
      2001, both our research group and Takemoto's group separately described an
      asymmetric allylation of glycine imino esters with allyl acetate catalyzed by
      palladium complexes and chiral ammonium salts. In these cases, the oxidative
      addition of palladium complexes to allyl acetate formed the pi-allylic fragments,
      while the chiral ammonium salts were actually responsible for controlling the
      stereoselectivity. These reactions in fact marked the beginning of asymmetric
      organo/metal combined catalysis. Since then, asymmetric organocatalysis combined
      with metal catalysis, including cooperative catalysis, relay catalysis, and
      sequential catalysis, has been a versatile concept for the creation of unknown
      organic transformations. Sequential catalysis describes a one-pot reaction
      involving two or more incompatible catalytic cycles. Alternatively, cooperative
      and relay catalyses require high compatibility of principally distinct catalysts
      and will be the focus of this Account. The catalysts in cooperative catalytic
      reactions must be able to simultaneously and individually activate both
      substrates to drive a bond-forming reaction, while relay catalysis is basically
      defined as a cascade process in which two or more sequential bond-forming
      transformations are independently catalyzed by distinct catalysts. In the past
      decade, we have discovered a variety of binary catalytic systems consisting of
      metals, including Rh(II), Pd(0), Au(I), and Mg(II), and chiral organocatalysts,
      including chiral phosphoric acids and quinine-based bifunctional molecules, for
      cooperative catalysis and relay catalysis, allowing the accomplishment of many
      unprecedented asymmetric transformations. In this Account, these achievements
      will be summarized, particularly focusing on the description of the concept and
      proof of the concept, to demonstrate the robustness of combined organo/metal
      catalysis in the creation of efficient enantioselective transformations. In
      addition, elegant studies from other laboratories using chiral phosphoric
      acid/Au(I) for the establishment of asymmetric cascade reactions involving the
      carbon-carbon triple bond functionality and typical combined organo/metal
      catalytic systems, very recently disclosed, will also be highlighted.

PMID- 24911185
TI  - Cutaneous squamous cell carcinoma with osteoclast-like giant cells: a very rare
      variant of cutaneous squamous cell carcinoma.

PMID- 24911187
TI  - Oral tinidazole for refractory Trichomonas vaginitis.

PMID- 24911188
TI  - From physical chemistry to mass spectrometry to government lab manager in half a
      century.

PMID- 24911186
TI  - Structure-based discovery of the first allosteric inhibitors of cyclin-dependent
      kinase 2.
AB  - Allosteric targeting of protein kinases via displacement of the structural alphaC
      helix with type III allosteric inhibitors is currently gaining a foothold in drug
      discovery. Recently, the first crystal structure of CDK2 with an open allosteric
      pocket adjacent to the alphaC helix has been described, prospecting new
      opportunities to design more selective inhibitors, but the structure has not yet
      been exploited for the structure-based design of type III allosteric inhibitors.
      In this work we report the results of a virtual screening campaign that resulted
      in the discovery of the first-in-class type III allosteric ligands of CDK2. Using
      a combination of docking and post-docking analyses made with our tool BEAR, 7
      allosteric ligands (hit rate of 20%) with micromolar affinity for CDK2 were
      identified, some of them inhibiting the growth of breast cancer cell lines in the
      micromolar range. Competition experiments performed in the presence of the ATP
      competitive inhibitor staurosporine confirmed that the 7 ligands are truly
      allosteric, in agreement with their design. Of these, compound 2 bound CDK2 with
      an EC50 value of 3 MUM and inhibited the proliferation of MDA-MB231 and ZR-75-1
      breast cancer cells with IC50 values of approximately 20 MUM, while compound 4
      had an EC50 value of 71 MUM and IC50 values around 4 MUM. Remarkably, the most
      potent compound 4 was able to selectively inhibit CDK2-mediated Retinoblastoma
      phosphorylation, confirming that its mechanism of action is fully compatible with
      a selective inhibition of CDK2 phosphorylation in cells. Finally, hit expansion
      through analog search of the most potent inhibitor 4 revealed an additional
      ligand 4g with similar in vitro potency on breast cancer cells.

PMID- 24911190
TI  - Nanocrystal synthesis in microfluidic reactors: where next?
AB  - The past decade has seen a steady rise in the use of microfluidic reactors for
      nanocrystal synthesis, with numerous studies reporting improved reaction control
      relative to conventional batch chemistry. However, flow synthesis procedures
      continue to lag behind batch methods in terms of chemical sophistication and the
      range of accessible materials, with most reports having involved simple one- or
      two-step chemical procedures directly adapted from proven batch protocols. Here
      we examine the current status of microscale methods for nanocrystal synthesis,
      and consider what role microreactors might ultimately play in laboratory-scale
      research and industrial production. 

PMID- 24911189
TI  - Secondary ion mass spectrometry imaging of Dictyostelium discoideum aggregation
      streams.
AB  - High resolution imaging mass spectrometry could become a valuable tool for cell
      and developmental biology, but both, high spatial and mass spectral resolution
      are needed to enable this. In this report, we employed Bi3 bombardment time-of
      flight (Bi3 ToF-SIMS) and C60 bombardment Fourier transform ion cyclotron
      resonance secondary ion mass spectrometry (C60 FTICR-SIMS) to image Dictyostelium
      discoideum aggregation streams. Nearly 300 lipid species were identified from the
      aggregation streams. High resolution mass spectrometry imaging (FTICR-SIMS)
      enabled the generation of multiple molecular ion maps at the nominal mass level
      and provided good coverage for fatty acyls, prenol lipids, and sterol lipids. The
      comparison of Bi3 ToF-SIMS and C60 FTICR-SIMS suggested that while the first
      provides fast, high spatial resolution molecular ion images, the chemical
      complexity of biological samples warrants the use of high resolution analyzers
      for accurate ion identification. 

PMID- 24911191
TI  - Analysis of run-to-run variation of bar-coded pyrosequencing for evaluating
      bacterial community shifts and individual taxa dynamics.
AB  - Bar-coded pyrosequencing has been increasingly used due to its fine taxonomic
      resolution and high throughput. Yet, concerns arise regarding the reproducibility
      of bar-coded pyrosequencing. We evaluated the run-to-run variation of bar-coded
      pyrosequencing in detecting bacterial community shifts and taxa dynamics. Our
      results demonstrate that pyrosequencing is reproducible in evaluating community
      shifts within a run, but not between runs. Also, the reproducibility of
      pyrosequencing in detecting individual taxa increased as a function of taxa
      abundance. Based on our findings: (1) for studies with modest sequencing depth,
      it is doubtful that data from different pyrosequencing runs can be considered
      comparable; (2) if multiple pyrosequencing runs are needed to increase the
      sequencing depth, additional sequencing efforts should be applied to all samples,
      rather than to selected samples; (3) if pyrosequencing is used for estimating
      bacterial population dynamics, only the abundant taxa should be considered; (4)
      for less-abundant taxa, the sequencing depth should be increased to ensure an
      accurate evaluation of taxon variation trends across samples. 

PMID- 24911192
TI  - Volitional electromyographic responses in disorders of consciousness.
AB  - OBJECTIVE: The aim of the study was to validate the use of electromyography (EMG)
      for detecting responses to command in patients in vegetative state/unresponsive
      wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS). METHODS:
      Thirty-eight patients were included in the study (23 traumatic, 25 patients >1
      year post-onset), 10 diagnosed as being in VS/UWS, eight in MCS- (no response to
      command) and 20 in MCS+ (response to command). Eighteen age-matched controls
      participated in the experiment. The paradigm consisted of three commands (i.e.
      'Move your hands', 'Move your legs' and 'Clench your teeth') and one control
      sentence (i.e. 'It is a sunny day') presented in random order. Each auditory
      stimulus was repeated 4 times within one block with a stimulus-onset asynchrony
      of 30 seconds. RESULTS: Post-hoc analyses with Bonferroni correction revealed
      that EMG activity was higher solely for the target command in one patient in
      permanent VS/UWS and in three patients in MCS+. CONCLUSION: The use of EMG could
      help clinicians to detect conscious patients who do not show any volitional
      response during standard behavioural assessments. However, further investigations
      should determine the sensitivity of EMG as compared to neuroimaging and
      electrophysiological assessments.

PMID- 24911193
TI  - The electronic health record: moving toward the goal of nursing diagnosis
      decision support.

PMID- 24911194
TI  - Age-related differences in glucose abnormalities in women with ST-elevation
      myocardial infarction submitted to percutaneous coronary intervention: a single
      center experience.
AB  - No datum is so far available on the relation between age and the acute glucose
      response to stress in women with ST-elevation myocardial infarction (STEMI)
      treated with percutaneous coronary intervention (PCI).We evaluated the age
      related differences in the acute glucose response in 373 STEMI women submitted to
      PCI. The oldest women, when compared to the other age subgroups, showed the
      higher admission and peak glycemia (P < 0.001 and P < 0.001, respectively) in the
      lack of differences in insulin, C-peptide, hemoglobin-glycated values and
      discharge glycemia values. At logistic regression analysis, the following
      variables were independent predictors of in-Intensive Cardiac Care Unit
      mortality: age (1-year step) [odds ratio 1.09, 96% confidence interval (CI) 1.04
      1.15, P = 0.001], admission glycemia (1g/l step) (odds ratio 2.05, 96% CI 1.35
      3.12, P < 0.001). At Cox regression analysis the following variables were
      associated with 1-year mortality (when adjusted for discharge glycemia): age (1
      year step) (hazard ratio 1.13, 95% CI 1.04-1.22, P = 0.005), estimated glomerular
      filtration rate (1 g/l step) (hazard ratio 0.93, 95% CI 0.90-0.96, P < 0.001).Age
      affects the acute glucose response to myocardial injury since older women showed
      the higher admission glucose values and the poorer in-hospital glucose control,
      in the lack of differences of insulin-resistance incidence. Glucose values were
      independent predictors of in-hospital mortality, but were not related to long
      term survival.

PMID- 24911195
TI  - alpha-1 Protein evaluation to stratify heart failure patients.

PMID- 24911196
TI  - Implementation of diagnosis in asymptomatic patients with aortic stenosis: the
      Implementation of Diagnosis in asymptomatic patiEnts with Aortic Stenosis
      registry.
AB  - Frequently in clinical practice, some physicians refer patients with aortic
      stenosis for an invasive approach in the asymptomatic phase of the disease. This
      empirical behaviour, which is in contrast with the recommendations of the current
      international clinical guidelines, is due to the perception that the prognosis of
      these patients is truly worse than retained. Actually, the management of
      asymptomatic patients with aortic stenosis remains controversial, and there is no
      clear agreement on how to reduce excess clinical events associated with the
      presence of aortic stenosis mortality and morbidity demonstrated in these
      patients by recent randomized clinical trials. The prevailing attention of the
      attending physicians is often limited to the assessment of the aortic stenosis
      severity and appearance of symptoms, but it has been clearly shown, instead, that
      the prognosis of these patients is associated with excessive left-ventricular
      mass growth and increased atherosclerosis leading to coronary artery disease,
      heart failure, stroke and death. Thus, apart from the markers of faster aortic
      stenosis progression, many other clinical and echocardiographic variables should
      be considered, collected and used together with the clinical/echocardiographic
      prognostic scores recently validated by several authors in clinical practice,
      where the vast majority of these variables are guiltily not taken into any
      consideration. The registry on the Implementation of Diagnosis in asymptomatic
      patiEnts with Aortic Stenosis is a prospective study designed with the aim to
      improve the diagnostic evaluation and improve the prognostic stratification of
      patients with asymptomatic aortic stenosis. 

PMID- 24911197
TI  - Synthesis of fluorenones through rhodium-catalyzed intramolecular acylation of
      biarylcarboxylic acids.
AB  - An efficient approach to the synthesis of fluorenones via the rhodium-catalyzed
      intramolecular acylation of biarylcarboxylic acids was developed. Using this
      procedure, fluorenones with various substituents can be synthesized in good to
      high yields. This work marks the first recorded use of catalytic intramolecular
      acylation to synthesize fluorenones. 

PMID- 24911198
TI  - Zinc and selenium levels in women with gestational diabetes mellitus at Medani
      Hospital, Sudan.
AB  - Gestational diabetes is a common medical disorder in pregnancy. There is a
      growing body of evidence of the association between zinc, selenium status and
      diabetes mellitus during pregnancy. A case-control study was conducted at Medani
      Hospital, Sudan, to compare zinc and selenium levels in pregnant women with
      gestational diabetes and normal pregnant women (controls). The two groups (31 in
      each arm) were well-matched in age, parity, gestational age, haemoglobin and body
      mass index. Zinc and selenium levels were measured using atomic absorption
      spectrophotometry. There were no significant differences in the median
      (interquartile) zinc (498.9 [395-703] vs 486.4 [404-667] MUg/l, p = 0.905) and
      selenium (164.4 [61-415] vs 204 [68-541] MUg/l, p = 0.838) values between the two
      groups. There were no significant correlations between zinc and selenium, or
      between these trace elements and body mass index, gestational age and blood
      glucose levels.

PMID- 24911199
TI  - Inhibitory role of polyunsaturated fatty acids on lysophosphatidic acid-induced
      cancer cell migration and adhesion.
AB  - Polyunsaturated fatty acids (PUFAs) have important pharmacological effects on
      mammalian cells. Here, we show that carboxyl group-containing PUFAs inhibit
      lysophosphatidic acid (LPA)-induced focal adhesion formation, thereby inhibiting
      migration and adhesion. Carboxyl group-containing PUFAs inhibit LPA-induced
      calcium mobilization, whereas ethyl ester-group containing PUFAs have no effect.
      In addition, carboxyl group-containing PUFAs functionally inhibit LPA-dependent
      RhoA activation. Given these results, we suggest that PUFAs may inhibit LPA
      induced calcium/RhoA signaling pathways leading to focal adhesion formation.
      Carboxyl group-containing PUFAs may have a functional role in this regulatory
      mechanism. 

PMID- 24911200
TI  - Functional diversity along the transverse axis of hippocampal area CA1.
AB  - Decades of neuroscience research have shed light on the hippocampus as a key
      structure for the formation of episodic memory. The hippocampus is divided into
      distinct subfields - CA1, CA2 and CA3. While accumulating evidence points to
      cellular and synaptic heterogeneity within each subfield, this heterogeneity has
      not received much attention in computational and behavioural studies and
      subfields have until recently been considered functionally uniform. However, a
      couple of recent studies have demonstrated prominent functional differences along
      the proximodistal axis of the CA1 subfield. Here, we review anatomical and
      physiological differences that might give rise to heterogeneity along the
      proximodistal axis of CA1 as well as the functional implications of such
      heterogeneity. We suggest that such heterogeneity in CA1 operates dynamically in
      the sense that the CA1 network alternates, on a subsecond scale, between a state
      where the network is primarily responsive to functionally segregated direct
      inputs from entorhinal cortex and a state where cells predominantly are
      controlled by more integrated inputs from CA3. 

PMID- 24911201
TI  - Membrane microdomains in immunoreceptor signaling.
AB  - Membrane microdomains denoted commonly as lipid rafts (or membrane rafts) have
      been implicated in T-cell receptor (TCR), and more generally immunoreceptor,
      signaling for over 25 years. However, this area of research has been complicated
      by doubts about the real nature (and even existence) of these membrane entities,
      especially because of methodological problems connected with possible detergent
      artefacts. Recent progress in biophysical approaches and functional studies of
      raft resident proteins apparently clarified many controversial aspects in this
      area. At present, the prevailing view is that these membrane microdomains are
      indeed involved in many aspects of cell biology, including immunoreceptor
      signaling. Moreover, several other types of raft-like microdomains (perhaps
      better termed nanodomains) have been described, which apparently also play
      important biological roles.

PMID- 24911202
TI  - Separation of zinc-dependent and zinc-independent events during early LPS
      stimulated TLR4 signaling in macrophage cells.
AB  - Free zinc is required for proper lipopolysaccharide (LPS)-stimulated signaling,
      but potential sites of action in the pathway have not been defined. In this work,
      we provide in vitro and ex vivo evidence that zinc is not required for
      phosphorylation or ubiquitylation of IRAK1, a kinase functioning early in the
      TLR4 pathway. However, degradation of ubiquitylated IRAK1 occurred via a zinc
      dependent, proteasome-independent pathway. These results provide evidence of a
      novel site of action for zinc during TLR4-mediated inflammatory responses. 

PMID- 24911203
TI  - A trip in the "New Microbiology" with the bacterial pathogen Listeria
      monocytogenes.
AB  - Listeria monocytogenes is a food-borne pathogen causing an opportunistic disease
      called listeriosis. This bacterium invades and replicates in most cell types, due
      to its multiple strategies to exploit host molecular mechanisms. Research aiming
      at unravelling Listeria invasion and intracellular lifestyle has led to a number
      of key discoveries in infection biology, cell biology and also microbiology. In
      this review, we report on our most recent advances in understanding the intimate
      crosstalk between the bacterium and its host, resulting from in-depth studies
      performed over the past five years. We specifically highlight new concepts in RNA
      based regulation in bacteria and discuss important findings in cell biology,
      including a new role for clathrin and an atypical mitochondrial fragmentation
      mechanism. We also illustrate the notion that bacterial infection regulates host
      gene expression at the chromatin level, contributing to an emerging field called
      patho-epigenetics. This review corresponds to the lecture given by one of us
      (P.C.) on the occasion of the 2014 FEBS|EMBO Woman in Science Award. 

PMID- 24911205
TI  - Neuronal circuits and computations: pattern decorrelation in the olfactory bulb.
AB  - Neuronal circuits in the olfactory bulb transform odor-evoked activity patterns
      across the input channels, the olfactory glomeruli, into distributed activity
      patterns across the output neurons, the mitral cells. One computation associated
      with this transformation is a decorrelation of activity patterns representing
      similar odors. Such a decorrelation has various benefits for the classification
      and storage of information by associative networks in higher brain areas.
      Experimental results from adult zebrafish show that pattern decorrelation
      involves a redistribution of activity across the population of mitral cells.
      These observations imply that pattern decorrelation cannot be explained by a
      global scaling mechanism but that it depends on interactions between distinct
      subsets of neurons in the network. This article reviews insights into the network
      mechanism underlying pattern decorrelation and discusses recent results that link
      pattern decorrelation in the olfactory bulb to odor discrimination behavior. 

PMID- 24911206
TI  - Expression of recombinant full-length plant phytochromes assembled with
      phytochromobilin in Pichia pastoris.
AB  - We have successfully developed a system to produce full-length plant phytochrome
      assembled with phytochromobilin in Pichia pastoris by co-expressing
      apophytochromes and chromophore biosynthetic genes, heme oxygenase (HY1) and
      phytochromobilin synthase (HY2) from Arabidopsis. Affinity-purified phytochrome
      proteins from Pichia cells displayed zinc fluorescence indicating chromophore
      attachment. Spectroscopic analyses showed absorbance maximum peaks identical to
      in vitro reconstituted phytochromobilin-assembled phytochromes, suggesting that
      the co-expression system is effective to generate holo-phytochromes. Moreover,
      mitochondria localization of the phytochromobilin biosynthetic genes increased
      the efficiency of holophytochrome biosynthesis. Therefore, this system provides
      an excellent source of holophytochromes, including oat phytochrome A and
      Arabidopsis phytochrome B. 

PMID- 24911204
TI  - Mitochondrial protein synthesis: figuring the fundamentals, complexities and
      complications, of mammalian mitochondrial translation.
AB  - Mitochondrial protein synthesis is essential for all mammals, being responsible
      for providing key components of the oxidative phosphorylation complexes. Although
      only thirteen different polypeptides are made, the molecular details of this
      deceptively simple process remain incomplete. Central to this process is a non
      canonical ribosome, the mitoribosome, which has evolved to address its unique
      mandate. In this review, we integrate the current understanding of the molecular
      aspects of mitochondrial translation with recent advances in structural biology.
      We identify numerous key questions that we will need to answer if we are to
      increase our knowledge of the molecular mechanisms underlying mitochondrial
      protein synthesis. 

PMID- 24911207
TI  - Molecular mechanisms of the circadian clockwork in mammals.
AB  - Circadian rhythms enable organisms to co-ordinate biological processes with the
      predictable 24 h cycle of day and night. Given that molecular clocks that
      coordinate such biological timing have evolved in almost all organisms, it is
      clear that being synchronous with the external environment confers competitive
      advantage. Conversely, it is apparent that being out of phase is detrimental,
      resulting in a number of clinical conditions, many of which are linked to
      metabolic dysfunction. The canonical clockwork involves a core set of genes that
      negatively regulate themselves through a so-called transcription translation
      feedback loop. However, recent studies describing evolutionarily conserved
      oscillations in redox reactions link circadian rhythms to metabolic processes,
      and in particular, redox pathways. In this review we describe the evidence for
      the interaction between transcriptional loops, redox and metabolism in mammals
      and suggest the clock may be potential target for the treatment of disease.

PMID- 24911208
TI  - Characterization of the contractile P2Y14 receptor in mouse coronary and cerebral
      arteries.
AB  - Extracellular UDP-glucose can activate the purinergic P2Y14 receptor. The aim of
      the present study was to examine the physiological importance of P2Y14 receptors
      in the vasculature. The data presented herein show that UDP-glucose causes
      contraction in mouse coronary and basilar arteries. The EC50 values and
      immunohistochemistry illustrated the strongest P2Y14 receptor expression in the
      basilar artery. In the presence of pertussis toxin, UDP-glucose inhibited
      contraction in coronary arteries and in the basilar artery it surprisingly caused
      relaxation. After organ culture of the coronary artery, the EC50 value decreased
      and an increased staining for the P2Y14 receptor was observed, showing receptor
      plasticity. 

PMID- 24911209
TI  - Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial
      phagocytosis.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine,
      expressed in many brain pathologies and associated with neuronal loss. We show
      here that addition of TNF-alpha to neuronal-glial co-cultures increases
      microglial proliferation and phagocytosis, and results in neuronal loss that is
      prevented by eliminating microglia. Blocking microglial phagocytosis by
      inhibiting phagocytic vitronectin and P2Y6 receptors, or genetically removing
      opsonin MFG-E8, prevented TNF-alpha induced loss of live neurons. Thus TNF-alpha
      appears to induce neuronal loss via microglial activation and phagocytosis of
      neurons, causing neuronal death by phagoptosis. 

PMID- 24911210
TI  - Transitional cell-type papillary carcinoma of the lacrimal sac manifesting as a
      medial canthal skin lesion.
AB  - A 61-year-old man presented with a 2.5 cm fungating skin lesion above the right
      medial canthus, accompanied by fluctuance and subtle inferotemporal globe
      displacement. The tumor had erupted 2 months previously and grown rapidly.
      Computed tomography (CT) revealed a 4.2 * 2.8 * 2.1 cm exophytic mass of the
      right orbit, superimposed on chronic dacryocystitis. Incisional biopsy disclosed
      faulty epithelial maturation sequence with possible basement membrane invasion.
      The patient underwent wide excision with medial maxillectomy, inferior
      turbinectomy, ethmoidectomy, and partial rhinectomy. The orbital floor was then
      reconstructed; a paramedian forehead flap and myocutaneous cheek advancement flap
      were used to fill cutaneous defects. All surgical margins were negative on both
      frozen and permanent sections. Definitive histopathology was consistent with
      transitional cell type papillary carcinoma of the lacrimal sac. Adjuvant
      radiotherapy was recommended, but the patient has declined further treatment. He
      remains recurrence-free at one year.

PMID- 24911212
TI  - Mechanistic insight into transition metal-catalyzed reaction of enynal/enynone
      with alkenes: metal-dependent reaction pathway.
AB  - A systematic study of the transition metal-catalyzed reaction of enynal/enynone
      with alkenes has been reported. It was found that the reaction has two metal
      dependent reaction pathways. One led to the formation of 1,2-DHN, while another
      led to cyclic-o-QDM. 

PMID- 24911211
TI  - The ARL2 GTPase is required for mitochondrial morphology, motility, and
      maintenance of ATP levels.
AB  - ARF-like 2 (ARL2) is a member of the ARF family and RAS superfamily of regulatory
      GTPases, predicted to be present in the last eukaryotic common ancestor, and
      essential in a number of model genetic systems. Though best studied as a
      regulator of tubulin folding, we previously demonstrated that ARL2 partially
      localizes to mitochondria. Here, we show that ARL2 is essential to a number of
      mitochondrial functions, including mitochondrial morphology, motility, and
      maintenance of ATP levels. We compare phenotypes resulting from ARL2 depletion
      and expression of dominant negative mutants and use these to demonstrate that the
      mitochondrial roles of ARL2 are distinct from its roles in tubulin folding.
      Testing of current models for ARL2 actions at mitochondria failed to support
      them. Rather, we found that knockdown of the ARL2 GTPase activating protein (GAP)
      ELMOD2 phenocopies two of three phenotypes of ARL2 siRNA, making it a likely
      effector for these actions. These results add new layers of complexity to ARL2
      signaling, highlighting the need to deconvolve these different cell functions. We
      hypothesize that ARL2 plays essential roles inside mitochondria along with other
      cellular functions, at least in part to provide coupling of regulation between
      these essential cell processes. 

PMID- 24911214
TI  - Docking-based 3D-QSAR study of pyridyl aminothiazole derivatives as checkpoint
      kinase 1 inhibitors.
AB  - Checkpoint kinase 1 (Chk1) is a promising target for the design of novel
      anticancer agents. In the present work, molecular docking simulations and three
      dimensional quantitative structure-activity relationship (3D-QSAR) studies were
      performed on pyridyl aminothiazole derivatives as Chk1 inhibitors. AutoDock was
      used to determine the probable binding conformations of all the compounds inside
      the active site of Chk1. Comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA) models were developed
      based on the docking conformations and alignments. The CoMFA model produced
      statistically significant results with a cross-validated correlation coefficient
      (q2) of 0.608 and a coefficient of determination (r2) of 0.972. The reliable
      CoMSIA model with q2 of 0.662 and r2 of 0.970 was obtained from the combination
      of steric, electrostatic and hydrogen bond acceptor fields. The predictive power
      of the models were assessed using an external test set of 14 compounds and showed
      reasonable external predictabilities (r(2)pred) of 0.668 and 0.641 for CoMFA and
      CoMSIA models, respectively. The models were further evaluated by leave-ten-out
      cross-validation, bootstrapping and progressive scrambling analyses. The study
      provides valuable information about the key structural elements that are required
      in the rational design of potential drug candidates of this class of Chk1
      inhibitors.

PMID- 24911213
TI  - Does thermal variability experienced at the egg stage influence life history
      traits across life cycle stages in a small invertebrate?
AB  - Although effects of thermal stability on eggs have often been considered in
      vertebrates, there is little data thermal stability in insect eggs even though
      these eggs are often exposed in nature to widely fluctuating ambient conditions.
      The modularity of development in invertebrates might lead to compensation across
      life cycle stages but this remains to be tested particularly within the context
      of realistic temperature fluctuations encountered in nature. We simulated natural
      temperate fluctuations on eggs of the worldwide cruciferous insect pest, the
      diamondback moth (DBM), Plutella xylostella (L.), while maintaining the same mean
      temperature (25 degrees C+/-0 degrees C, 25+/-4 degrees C, 25+/-6 degrees C, 25+/
      8 degrees C, 25+/-10 degrees C, 25+/-12 degrees C) and assessed egg development,
      survival and life history traits across developmental stages. Moderate
      fluctuations (25+/-4 degrees C, 25+/-6 degrees C) did not influence performance
      compared to the constant temperature treatment, and none of the treatments
      influenced egg survival. However the wide fluctuating temperatures (25+/-10
      degrees C, 25+/-12 degrees C) slowed development time and led to an increase in
      pre-pupal mass, although these changes did not translate into any effects on
      longevity or fecundity at the adult stage. These findings indicate that
      environmental effects can extend across developmental stages despite the
      modularity of moth development but also highlight that there are few fitness
      consequences of the most variable thermal conditions likely to be experienced by
      Plutella xylostella. 

PMID- 24911215
TI  - Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells.
AB  - The present studies were to determine whether the multi-kinase inhibitor
      sorafenib or its derivative regorafenib interacted with the ERBB1/ERBB2 inhibitor
      lapatinib to kill CNS tumor cells. In multiple CNS tumor cell types sorafenib and
      lapatinib interacted in a greater than additive fashion to cause tumor cell
      death. Tumor cells lacking PTEN, and anoikis or lapatinib resistant cells were as
      sensitive to the drug combination as cells expressing PTEN or parental cells,
      respectively. Similar data were obtained using regorafenib. Treatment of brain
      cancer cells with [sorafenib + lapatinib] enhanced radiation toxicity. The drug
      combination increased the numbers of LC3-GFP vesicles; this correlated with a
      reduction in endogenous LC3II, and p62 and LAMP2 degradation. Knock down of
      Beclin1 or ATG5 significantly suppressed drug combination lethality. Expression
      of c-FLIP-s, BCL-XL, or dominant negative caspase 9 reduced drug combination
      toxicity; knock down of FADD or CD95 was protective. Expression of both activated
      AKT and activated MEK1 or activated mTOR was required to strongly suppress drug
      combination lethality. As both lapatinib and sorafenib are FDA approved agents,
      our data argue for further determination as to whether lapatinib and sorafenib is
      a useful glioblastoma therapy.

PMID- 24911218
TI  - Guest-induced symmetry lowering of an ionic clathrate material for carbon
      capture.
AB  - We report a new lattice structure of the ionic clathrate hydrate of tetra-n
      butylammonium bromide induced by guest CO2 molecules, which is found to provide
      high CO2 storage capacity. The structure was characterized by a set of methods,
      including single crystal X-ray diffraction, NMR, and MD simulations. 

PMID- 24911216
TI  - Statins and physical activity in older men: the osteoporotic fractures in men
      study.
AB  - IMPORTANCE: Muscle pain, fatigue, and weakness are common adverse effects of
      statin medications and may decrease physical activity in older men. OBJECTIVE: To
      determine whether statin use is associated with physical activity, longitudinally
      and cross-sectionally. DESIGN, SETTING, AND PARTICIPANTS: Men participating in
      the Osteoporotic Fractures in Men Study (N = 5994), a multicenter prospective
      cohort study of community-living men 65 years and older, enrolled between March
      2000 and April 2002. Follow-up was conducted through 2009. EXPOSURES: Statin use
      as determined by an inventory of medications (taken within the last 30 days). In
      cross-sectional analyses (n = 4137), statin use categories were users and
      nonusers. In longitudinal analyses (n = 3039), categories were prevalent users
      (baseline use and throughout the study), new users (initiated use during the
      study), and nonusers (never used). MAIN OUTCOMES AND MEASURES: Self-reported
      physical activity at baseline and 2 follow-up visits using the Physical Activity
      Scale for the Elderly (PASE). At the third visit, an accelerometer measured
      metabolic equivalents (METs [kilocalories per kilogram per hour]) and minutes of
      moderate activity (METs >=3.0), vigorous activity (METs >=6.0), and sedentary
      behavior (METs <=1.5). RESULTS: At baseline, 989 men (24%) were users and 3148
      (76%) were nonusers. The adjusted difference in baseline PASE between users and
      nonusers was -5.8 points (95% CI, -10.9 to -0.7 points). A total of 3039 men met
      the inclusion criteria for longitudinal analysis: 727 (24%) prevalent users, 845
      (28%) new users, and 1467 (48%) nonusers. PASE score declined by a mean (95% CI)
      of 2.5 (2.0 to 3.0) points per year for nonusers and 2.8 (2.1 to 3.5) points per
      year for prevalent users, a nonstatistical difference (0.3 [-0.5 to 1.0] points).
      For new users, annual PASE score declined at a faster rate than nonusers
      (difference of 0.9 [95% CI, 0.1 to 1.7] points). A total of 3071 men had adequate
      accelerometry data, 1542 (50%) were statin users. Statin users expended less METs
      (0.03 [95% CI, 0.02-0.04] METs less) and engaged in less moderate physical
      activity (5.4 [95% CI, 1.9-8.8] fewer minutes per day), less vigorous activity
      (0.6 [95% CI, 0.1-1.1] fewer minutes per day), and more sedentary behavior (7.6
      [95% CI, 2.6-12.4] greater minutes per day). CONCLUSIONS AND RELEVANCE: Statin
      use was associated with modestly lower physical activity among community-living
      men, even after accounting for medical history and other potentially confounding
      factors. The clinical significance of these findings deserves further
      investigation.

PMID- 24911217
TI  - Residential levels of polybrominated diphenyl ethers and risk of childhood acute
      lymphoblastic leukemia in California.
AB  - BACKGROUND: House dust is a major source of exposure to polybrominated diphenyl
      ethers (PBDEs), which are found at high levels in U.S. homes. METHODS: We studied
      167 acute lymphoblastic leukemia (ALL) cases 0-7 years of age and 214 birth
      certificate controls matched on date of birth, sex, and race/ethnicity from the
      Northern California Childhood Leukemia Study. In 2001-2007, we sampled carpets in
      the room where the child spent the most time while awake; we used a high-volume
      small-surface sampler or we took dust from the home vacuum. We measured
      concentrations of 14 PBDE congeners including penta (28, 47, 99, 100, 153, 154),
      octa (183, 196, 197, 203), and decaBDEs (206-209). Odds ratios (ORs) were
      calculated using logistic regression, adjusting for demographics, income, year of
      dust collection, and sampling method. RESULTS: BDE-47, BDE-99, and BDE-209 were
      found at the highest concentrations (medians, 1,173, 1,579, and 938 ng/g,
      respectively). Comparing the highest to lowest quartile, we found no association
      with ALL for summed pentaBDEs (OR = 0.7; 95% CI: 0.4, 1.3), octaBDEs (OR = 1.3;
      95% CI: 0.7, 2.3), or decaBDEs (OR = 1.0; 95% CI: 0.6, 1.8). Comparing homes in
      the highest concentration (nanograms per gram) tertile to those with no
      detections, we observed significantly increased ALL risk for BDE-196 (OR = 2.1;
      95% CI: 1.1, 3.8), BDE-203 (OR = 2.0; 95% CI: 1.1, 3.6), BDE-206 (OR = 2.1; 95%
      CI: 1.1, 3.9), and BDE-207 (OR = 2.0; 95% CI: 1.03, 3.8). CONCLUSION: We found no
      association with ALL for common PBDEs, but we observed positive associations for
      specific octa and nonaBDEs. Additional studies with repeated sampling and
      biological measures would be informative.

PMID- 24911219
TI  - Percutaneous tibial nerve stimulation vs sacral nerve stimulation for faecal
      incontinence: a comparative case-matched study.
AB  - AIM: The study assessed the initial experience with posterior tibial nerve
      stimulation (PTNS) for faecal incontinence and compared it with sacral nerve
      stimulation (SNS) performed in a single centre during the same timespan. METHOD:
      A retrospective review of a prospectively collected database was conducted at the
      colorectal unit, University Hospital, Nantes, France, from May 2009 to December
      2010. Seventy-eight patients diagnosed with chronic severe faecal incontinence
      underwent neurostimulation including PTNS in 21 and SNS in 57. The main outcome
      measures were faecal incontinence (Wexner score) and quality of life (Fecal
      Incontinence Quality of Life, FIQL) scores in a short-term follow-up. RESULTS: No
      significant differences were observed in patients' characteristics. Of 57
      patients having SNS, 18 (32%) failed peripheral nerve evaluation and 39 (68%)
      received a permanent implant. Two (5%) developed a wound infection. No adverse
      effects were recorded in the PTNS group. There was no significant difference in
      the mean Wexner and FIQL scores between patients having PTNS and SNS at 6 (P =
      0.39 and 0.09) and 12 months (P = 0.79 and 0.37). A 50% or more improvement in
      Wexner score was seen at 6 and 12 months in 47% and 30% of PTNS patients and in
      50% and 58% of SNS patients with no significant difference between the groups.
      CONCLUSION: Posterior tibial nerve stimulation is a valid method of treating
      faecal incontinence in the short term when conservative treatment has failed. It
      is easier, simpler, cheaper and less invasive than SNS with a similar short-term
      outcome.

PMID- 24911220
TI  - Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and
      alkeran in multiple myeloma autologous transplantation.
AB  - Propylene Glycol-Free melphalan HCL for Injection (PGF-Mel) is a new formulation
      that incorporates Captisol, a specially modified cyclodextrin, to improve
      melphalan stability. In this phase IIa, open-label, randomized, cross-over design
      bioequivalence study, the pharmacokinetics of PGF-Mel were compared with the
      marketed formulation of melphalan, or Alkeran. Patients received half of the
      total dose of melphalan in the form of Alkeran and the other half in the form of
      PGF-Mel in an alternating manner. The pharmacokinetic measures were determined
      using WinNonlin 6.2 and bioequivalence was assessed using log-transformed
      systemic exposure parameters. Twenty-four patients, 11 females and 13 males, were
      enrolled between 4 February 2010 and 16 May 2011 at The University of Kansas
      Medical Center and The University of Kansas Cancer Center. The median age of
      enrolled subjects was 58 years (range: 48-65). All patients achieved
      myeloablation 3 days post autologous graft followed by successful neutrophil
      engraftment with a median of 11 days after transplant. Pharmacokinetic analysis
      showed that PGF-Mel was bioequivalent with Alkeran and also revealed that maximum
      plasma concentration (Cmax) and area under the plasma concentration-time curve
      (AUC) were higher (~10%) after PGF-Mel administration. In conclusion, PGF-Mel is
      considered bioequivalent to Alkeran while also demonstrating a marginally higher
      systemic drug exposure. 

PMID- 24911221
TI  - Investigation of older adults' participation in exercises following completion of
      a state-wide survey targeting evidence-based falls prevention strategies.
AB  - This paper examines whether involvement in an observational study may prompt
      participants to change their exercise behaviors. Data were collected from 394
      older community dwellers in Victoria, Australia using a baseline survey, and 245
      of these participated in a follow-up survey one year later. Survey domains were
      drawn from constructs of relevant health behavior models. Results showed that the
      proportion of respondents who were currently participating in exercises to
      prevent falls at follow-up was 12% higher than at baseline (Wilcoxon p value <
      .001). Twenty-nine percent reported they had changed their perceptions about
      falls and their risk of falls, with comments focused on threat appraisal. Forty
      four percent reported having taken strategies to reduce their risk of falling,
      with comments based on implementation of different preventive strategies.
      Respondents who held favorable views toward exercises for the prevention of falls
      appear to change their behaviors that might address falls when participating in
      observational studies. 

PMID- 24911222
TI  - Sticks and stones may break my bones, but what about words?
AB  - Helping children to use words to express their thoughts and feelings is the goal
      of psychodynamic group therapy. The subject of this paper was a group of boys in
      a weekly school-based counseling group. The article explores ways in which the
      boys could only discharge psychic tension in action and uncovers a fear of using
      words as a mode of expression. By conceptualizing what he calls "action-talk," a
      stage between the use of action and talk which sounds like talk, but is not, the
      author resolved resistances to progressive communication. The importance of being
      aware of the therapist's own need to control the direction of the group, tendency
      to avoid negative feelings, and the importance of open-ended, talk-based therapy
      approaches (versus curriculum-based or psychoeducational groups) are discussed.

PMID- 24911223
TI  - The application of group forgiveness intervention for courtship-hurt college
      students: a Chinese perspective.
AB  - Forgiveness intervention has been shown to be effective in dealing with problems
      caused by interpersonal hurt. Problems caused by courtship hurt could also be
      resolved by this approach. This paper describes the theoretical foundations and
      application of a group forgiveness treatment program which reflected some
      elements of collectivist Chinese culture positivity for individuals hurt in
      romantic relationships. Thirty-one female students from a Chinese university were
      randomly assigned to three groups (forgiveness group, general group, and control
      group). They completed a Scale of Courtship Forgiveness, the Beck Anxiety
      Inventory, the Beck Depression Inventory, and the Index of Well-Being & Index of
      General Affect at entry (baseline), at the end of treatment, and at a four-week
      follow-up. Compared with the control group, clients both from forgiveness and
      general groups showed significant improvement in anxiety, depression, and well
      being at the end of treatment, but only the forgiveness group showed significant
      improvement in courtship forgiveness. Further, the effectiveness of treatment for
      the forgiveness group lasted longer than for the general group. The findings
      suggest that the forgiveness treatment can be beneficial for college students
      hurt in romantic relationship.

PMID- 24911224
TI  - Social positions, scripts, and functioning dynamics: phenomenology of the
      Egyptian social unconscious.
AB  - This article explores the constituents, components, and manifestations of the
      Egyptian social unconscious. Noting that Bion's group basic assumptions are
      actually based on Klein's individual psychic positions (Paranoid-Schizoid and
      Depressive; PS-D), and can easily be extrapolated to the social large group, the
      author assumes that to communities, societies, and cultures the same assumptions
      may apply to some extent. Moreover, just as groups can move between basic
      assumption functioning and work functioning, so societies seem to do. Eric
      Berne's concept of an "individual life script" can also be extended to societies
      that can have a "social life script." This article is a step toward designing a
      "social unconscious" map for different countries and cultures that shows where on
      the PS-D spectrum a certain country is placed, what is a certain culture's
      "social life script," and how the dynamics of a certain society can be manifested
      in its people's behavior as either basic assumption or work functioning.

PMID- 24911225
TI  - Commentary on "Social positions, scripts, and functioning dynamics: phenomenology
      of the Egyptian social unconscious".

PMID- 24911226
TI  - Commentary on "Social positions, scripts, and functioning dynamics: phenomenology
      of the Egyptian social unconscious".

PMID- 24911227
TI  - Social repetition compulsion: deconstruction and reconstruction of the father.

PMID- 24911228
TI  - Evaluation of a group intervention for veterans who experienced military-related
      trauma.
AB  - Military-related trauma and veteran status have been linked with posttraumatic
      stress symptoms, depressive symptoms, and other personal and interpersonal
      difficulties. While many treatment evaluations for people with posttraumatic
      stress exist, few veteran populations or group formats have been evaluated. This
      report presents an evaluation of the Veterans Transition Program (VTP)-a group
      based treatment for veterans who experienced a military-related trauma that is
      negatively impacting their lives. Fifty-six veterans attended the VTP; all
      attended every session and completed pre- and post-tests assessing posttraumatic
      stress and depressive symptoms. Significant pre- to post-test improvement was
      found on all scales. These findings demonstrate the potential benefit of the VTP
      and encourage further research.

PMID- 24911229
TI  - Trauma-informed cognitive remediation group therapy.
AB  - This brief report presents the rationale for the importance of integrating trauma
      therapy with cognitive remediation in order to enhance both component
      interventions in the treatment of serious mental illness. It describes a general
      format that allows the above integration and suggests that future studies should
      investigate the efficacy of the proposed group design.

PMID- 24911230
TI  - Resistance and my favorite patient.

PMID- 24911232
TI  - Dialectical behavior group therapy for borderline personality disorder.

PMID- 24911238
TI  - Prolonged sound exposure has different effects on increasing neuronal size in the
      auditory cortex and brainstem.
AB  - Tone at moderate levels presented to young rats at a stage (postnatal week-4)
      presumably that has passed the cortical critical period still can enlarge neurons
      in the auditory cortex. It remains unclear whether this delayed plastic change
      occurs only in the cortex, or reflects a change taking place in the auditory
      brainstem. Here we compared sound-exposure effects on neuronal size in the
      auditory cortex and the midbrain. Starting from postnatal day 22, young rats were
      exposed to a low-frequency tone (4 kHz at 65 dB SPL) for a period of 3 (postnatal
      day 22-25) or 7 (postnatal day 22-29) days before sacrifice. Neurons were
      analyzed morphometrically from 7 MUm-thick histological sections. A marked
      increase in neuronal size (32%) was found at the cortex in the high-frequency
      region distant from the exposing tone. The increase in the midbrain was even
      larger (67%) and was found in both the low and high frequency regions. While cell
      enlargements were clear at day 29, only in the high frequency region of the
      cortex a slight enlargement was found at day 22, suggesting that the cortical and
      subcortical changes are synchronized, if not slightly preceded by the cortex. In
      contrast, no changes in neuronal size were found in the cochlear nucleus or the
      visual midbrain. Such differential effects of sound-exposure at the auditory
      centers across cortical and subcortical levels cannot be explained by a simple
      activity-driven change occurring earlier in the brainstem, and might involve
      function of other structures as for example the descending auditory system. 

PMID- 24911237
TI  - The auditory corticocollicular system: molecular and circuit-level
      considerations.
AB  - We live in a world imbued with a rich mixture of complex sounds. Successful
      acoustic communication requires the ability to extract meaning from those sounds,
      even when degraded. One strategy used by the auditory system is to harness high
      level contextual cues to modulate the perception of incoming sounds. An ideal
      substrate for this process is the massive set of top-down projections emanating
      from virtually every level of the auditory system. In this review, we provide a
      molecular and circuit-level description of one of the largest of these pathways:
      the auditory corticocollicular pathway. While its functional role remains to be
      fully elucidated, activation of this projection system can rapidly and profoundly
      change the tuning of neurons in the inferior colliculus. Several specific issues
      are reviewed. First, we describe the complex heterogeneous anatomical
      organization of the corticocollicular pathway, with particular emphasis on the
      topography of the pathway. We also review the laminar origin of the
      corticocollicular projection and discuss known physiological and morphological
      differences between subsets of corticocollicular cells. Finally, we discuss
      recent findings about the molecular micro-organization of the inferior colliculus
      and how it interfaces with corticocollicular termination patterns. Given the
      assortment of molecular tools now available to the investigator, it is hoped that
      his review will help guide future research on the role of this pathway in normal
      hearing. 

PMID- 24911239
TI  - The amino acid at residue 155 in nonstructural protein 4 of porcine reproductive
      and respiratory syndrome virus contributes to its inhibitory effect for
      interferon-beta transcription in vitro.
AB  - Type I interferons (IFNs), predominantly IFN-alpha and beta, play important roles
      in both innate and adaptive immune responses against viral infections. Porcine
      reproductive and respiratory syndrome virus (PRRSV) has been recognized to be
      able to down-regulate the IFN response during in vivo and in vitro infection. In
      this study, we first analyzed inhibitory effect of each NSP of low pathogenic
      PRRSV HB-1/3.9 on IFN-beta transcription in MARC-145 cells, and the results
      showed that the IFN-beta promoter activation could be suppressed by NSP1alpha,
      NSP2, NSP1beta, NSP3, NSP4, NSP5 and NSP11. We next confirmed that the inhibitory
      effect of NSP4 was mainly mediated through suppressing NF-kappaB activation,
      whereas not hindering NF-kappaB phosphorylation and nuclear translocation, and
      nuclear-localized NSP4 was responsible for inhibiting IFN-beta activation. We
      further found that the NSP4 of different pathogenic PRRSV strains exhibited
      differential inhibitory effect on IFN-beta, NF-kappaB, and IRF3 transcription,
      and the NSP4 of highly pathogenic (HP)-PRRSV could display more strong inhibitory
      effect. Finally, we determined that the amino acid at residue 155 in NSP4
      contributed to its inhibitory effect for IFN-beta transcription in vitro by
      altering its subcellular distribution. Our findings suggest that the nucleus
      localized NSP4 of PRRSV participates in the modulation of the host type I IFNs
      system, and also provide novel insight for understanding the pathogenesis of the
      Chinese HP-PRRSV.

PMID- 24911243
TI  - Inverted substrate preferences for photochemical heterolysis arise from conical
      intersection control.
AB  - Heterolytic bond scission is a staple of chemical reactions. While qualitative
      and quantitative models exist for understanding the thermal heterolysis of carbon
      leaving group (C-LG) bonds, no general models connect structure to reactivity for
      heterolysis in the excited state. CASSCF conical intersection searches were
      performed to investigate representative systems that undergo photoheterolysis to
      generate carbocations. Certain classes of unstabilized cations are found to have
      structurally nearby, low-energy conical intersections, whereas stabilized cations
      are found to have high-energy, unfavorable conical intersections. The former
      systems are often favored from photochemical heterolysis, whereas the latter are
      favored from thermal heterolysis. These results suggest that the frequent
      inversion of the substrate preferences for nonadiabatic photoheterolysis
      reactions arises from switching from transition-state control in thermal
      heterolysis reactions to conical intersection control for photochemical
      heterolysis reactions. The elevated ground-state surfaces resulting from
      generating unstabilized or destabilized cations, in conjunction with stabilized
      excited-state surfaces, can lead to productive conical intersections along the
      heterolysis reaction coordinate. 

PMID- 24911240
TI  - Success of measles virotherapy in ATL depends on type I interferon secretion and
      responsiveness.
AB  - Adult T cell leukemia/lymphoma (ATL) is a highly aggressive CD4+/CD25+ T-cell
      malignancy caused by human T cell lymphotropic virus type 1 (HTLV-1). Previous
      studies in the MET-1 cell/NOD/SCID mouse model of ATL demonstrated that MET-1
      cells are very susceptible to measles virus (MV) oncolytic therapy. To further
      evaluate the potential of MV therapy in ATL, the susceptibility of several HTLV-1
      transformed CD4+ T cell lines (MT-1, MT-2, MT-4 and C8166-45) as well as HTLV-1
      negative CD4+ T cell lines (Jurkat and CCRF-CEM) to infection with MV was tested
      in vitro. All cell lines were permissive to MV infection and subsequent cell
      death, except MT-1 and CCRF-CEM cells which were susceptible and permissive to MV
      infection, but resistant to cell death. The resistance to MV-mediated cell death
      was associated with IFNbeta produced by MT-1 and CCRF-CEM cells. Inhibition of
      IFNbeta rendered MT-1 and CCRF-CEM cells susceptible to MV-mediated cell death.
      Cells susceptible to MV-induced cell death did not produce nor were responsive to
      IFNbeta. Upon infection with Newcastle Disease Virus (NDV), MT-1 and CCRF-CEM but
      not the susceptible cell lines up-regulated pSTAT-2. In vivo, treatment of tumors
      induced by MT-1 cell lines which produce IFNbeta demonstrated only small
      increases in mean survival time, while only two treatments prolonged mean
      survival time in mice with MET-1 tumors deficient in type I interferon
      production. These results indicate that type I interferon production is closely
      linked with the inability of tumor cells to respond to type I interferon.
      Screening of tumor cells for type I interferon could be a useful strategy to
      select candidate patients for MV virotherapy. 

PMID- 24911241
TI  - School mental health services: signpost for out-of-school service utilization in
      adolescents with mental disorders? A nationally representative United States
      cohort.
AB  - BACKGROUND: School mental health services are important contact points for
      children and adolescents with mental disorders, but their ability to provide
      comprehensive treatment is limited. The main objective was to estimate in
      mentally disordered adolescents of a nationally representative United States
      cohort the role of school mental health services as guide to mental health care
      in different out-of-school service sectors. METHODS: Analyses are based on
      weighted data (N = 6483) from the United States National Comorbidity Survey
      Replication Adolescent Supplement (participants' age: 13-18 years). Lifetime DSM
      IV mental disorders were assessed using the fully structured WHO CIDI interview,
      complemented by parent report. Adolescents and parents provided information on
      mental health service use across multiple sectors, based on the Service
      Assessment for Children and Adolescents. RESULTS: School mental health service
      use predicted subsequent out-of-school service utilization for mental disorders
      i) in the medical specialty sector, in adolescents with affective (hazard ratio
      (HR) = 3.01, confidence interval (CI) = 1.77-5.12), anxiety (HR = 3.87, CI = 1.97
      7.64), behavior (HR = 2.49, CI = 1.62-3.82), substance use (HR = 4.12, CI = 1.87
      9.04), and eating (HR = 10.72, CI = 2.31-49.70) disorders, and any mental
      disorder (HR = 2.97, CI = 1.94-4.54), and ii) in other service sectors, in
      adolescents with anxiety (HR = 3.15, CI = 2.17-4.56), behavior (HR = 1.99, CI =
      1.29-3.06), and substance use (HR = 2.48, CI = 1.57-3.94) disorders, and any
      mental disorder (HR = 2.33, CI = 1.54-3.53), but iii) not in the mental health
      specialty sector. CONCLUSIONS: Our findings indicate that in the United States,
      school mental health services may serve as guide to out-of-school service
      utilization for mental disorders especially in the medical specialty sector
      across various mental disorders, thereby highlighting the relevance of school
      mental health services in the trajectory of mental care. In light of the missing
      link between school mental health services and mental health specialty services,
      the promotion of a stronger collaboration between these sectors should be
      considered regarding the potential to improve and guarantee adequate mental care
      at early life stages.

PMID- 24911244
TI  - Effects of Group 1 versus Group 2 carbapenems on the susceptibility of
      Acinetobacter baumannii to carbapenems: a before and after intervention study of
      carbapenem-use stewardship.
AB  - OBJECTIVE: Antimicrobial stewardship programs have been proposed for reducing
      bacterial resistance in the hospital environment. The purpose of this study was
      to investigate the impact of a carbapenem-use stewardship program on the
      susceptibility of Acinetobacter baumannii to Group 2 carbapenems. METHODS: A
      before and after intervention study was conducted at a university hospital from
      September 2008 to February 2013. Three study periods were defined: Phase I, pre
      intervention (months 1-18); Phase II, a postintervention period during which
      ertapenem use was mandated but carbapenem use was not restricted (months 19-36);
      and Phase III, a postintervention period during which Group 2 carbapenem use was
      restricted (months 37-54). RESULTS: During the study period, intervention
      resulted in diminished consumption of Group 2 carbapenems (antimicrobial use
      density (AUD): 21.3+/-6.0 in Phase I, 18.8+/-6.0 in Phase II, 16.1+/-4.4 in Phase
      III; P = 0.028) and increased consumption of ertapenem (AUD: 2.7+/-1.7 in Phase
      I, 7.2+/-4.5 in Phase II, 9.1+/-5.3 in Phase III; P<0.001). The use of
      autoregressive-error models showed that in contrast with ertapenem use, the use
      of Group 2 carbapenem during the previous one month was positively and
      significantly associated with a subsequent increase in the proportion of
      carbapenem-resistant A. baumannii (CRAB) (P = 0.031). CONCLUSIONS: Implementing a
      carbapenem-use stewardship program featuring the preferential use of ertapenem
      for treating appropriate indications of infection resulted in reduced use of
      Group 2 carbapenems and had a positive impact on the susceptibility of A.
      baumannii to carbapenems. This approach could be integrated into CRAB-control
      strategies in hospitals.

PMID- 24911245
TI  - Pathway selection in peptide amphiphile assembly.
AB  - The nature of supramolecular structures could be strongly affected by the
      pathways followed during their formation just as mechanisms and final outcomes in
      chemical reactions vary with the conditions selected. So far this is a largely
      unexplored area of supramolecular chemistry. We demonstrate here how different
      preparation protocols to self-assemble peptide amphiphiles in water can result in
      the formation of different supramolecular morphologies, either long filaments
      containing beta-sheets or smaller aggregrates containing peptide segments in
      random coil conformation. We found that the assembly rate into beta-sheets
      decreases in the presence of a destabilizing "good" solvent like
      hexafluoroisopropanol (HFIP) and is affected by transient conditions in solution.
      Also the peptide amphiphile investigated spontaneously nucleates the beta-sheet
      containing filaments at a critical fraction of HFIP in water below 21%.
      Furthermore, beta-sheet assemblies have a high kinetic stability and, once
      formed, do not disassemble rapidly. We foresee that insights into the
      characteristic dynamics of a supramolecular system provide an efficient approach
      to select the optimum assembly pathway necessary for function. 

PMID- 24911246
TI  - A literature review of the current evidence for routine antibiotic prophylaxis
      after cervical tissue excisions.
AB  - Consistent data are available on supporting the routine use of prophylactic
      antibiotics for several obstetrical and gynaecological procedures. According to
      the Surgical Wounds Classification scheme, operations involving the vagina are
      included in the clean-contaminated category of procedures, and guidelines
      recommend the routine use of prophylactic antibiotics. The objective of this
      paper is to review the current evidence regarding prophylactic antibiotics for
      cervical tissue excisions. We performed a systematic search of medical databases
      to March 2014 and we found three randomised controlled trials reporting on the
      role of prophylactic antibiotics in 683 patients who underwent cervical
      excisions. When compared with controls, the prophylactic antibiotics group was
      similar in terms of postoperative bleeding, vaginal discharge, pain, incidence of
      adverse events, requirement of antibiotics and readmission rate secondary to
      bleeding. This systematic review based on three randomised controlled trials
      suggests that current evidence does not support the routine prophylactic
      antibiotics for cervical tissue excisions.

PMID- 24911248
TI  - Neighboring look-a-likes: distinguishing between breast and dermatologic lesions.
AB  - Due to the proximity of the skin, subcutis, and axilla to the breast, the
      possibility of a "breast mass" actually representing a dermatologic lesion should
      be considered, particularly if the proliferation does not look characteristically
      "mammary" in appearance. Even more underappreciated is the scenario of a
      dermatologic proliferation morphologically masquerading as a breast tumor. The
      pathologist can fall prey to this pitfall if he/she is led to believe that the
      location of the tumor is the breast proper. The aim of this review is to provide
      an overview of dermatologic mimickers of breast lesions and helpful ways to
      discern between them when possible. 

PMID- 24911247
TI  - Fungal infections of the gastrointestinal tract in the immunocompromised host: an
      update.
AB  - Fungal infections are one of the most significant causes of morbidity and
      mortality in immunocompromised patients. The incidence of invasive fungal
      infections, including those of the gastrointestinal tract, has increased
      significantly as numbers of immunocompromised patients have increased. The
      diagnosis of fungal infections in immunocompromised patients may be particularly
      problematic as these patients may present with atypical clinical features.
      Although Candida and Aspergillus species represent the majority of fungi
      diagnosed in the immunocompromised patient population, other fungi are emerging
      as increasingly common pathogens, and this review will focus on several important
      emerging fungal infections in immunocompromised patients. 

PMID- 24911249
TI  - Systemic lupus erythematosus-associated neutrophilic dermatosis: a review and
      update.
AB  - Neutrophilic dermatoses are a rare manifestation of systemic lupus erythematosus
      (SLE). In recent years, a growing body of literature describes a pathologic
      spectrum of neutrophilic infiltrates that may be seen in lupus patients. It is
      particularly important to recognize that neutrophilic dermatoses can be the
      initial manifestation of SLE in a third of patients. We were able to identify 47
      patients with SLE associated with neutrophilic tissue reactions. In this review,
      we describe the histologic and clinical features of these cases in the hope that
      increased awareness of this unusual manifestation of SLE will generate prompt
      diagnosis and improved patient care. 

PMID- 24911250
TI  - Epithelioid hemangioendothelioma of the bone: a review and update.
AB  - Epithelioid hemangioendothelioma is a vascular tumor of low to intermediate
      malignancy that was initially described in the soft tissue. Since then,
      epithelioid hemangioendothelioma has been described in various anatomic sites
      including parenchymal tissues and the bone. In the bone, these tumors must not
      only be distinguished from other vascular tumors that can arise in this location,
      primarily epithelioid hemangioma and epithelioid angiosarcoma, but also from
      metastatic carcinoma. Discussion of the historical context and the pertinent
      literature on the subject forms the basis of this review. 

PMID- 24911251
TI  - Follicular dendritic cell pattern in early lymphomas involving follicles.
AB  - This article reviews the most typical follicular dendritic cell (FDC) patterns
      displayed by early lymphomas involving follicles. In in situ follicular lymphoma,
      FDCs form a well-developed round (spherical) dendritic meshwork with a sharp
      outline. Other patterns that can be seen include
      contracted/distorted/disintegrated FDC meshworks. In early mantle cell lymphoma
      with mantle zone pattern, FDCs compose an ill-outlined and loosely arranged
      "centrifugal" meshwork. In marginal zone lymphoma, the FDC meshwork forms a
      relatively well-developed nodular meshwork with irregular outlines. In nodular
      lymphocyte predominant (LP) Hodgkin lymphoma, LP tumor cells are localized within
      an environment with prominent FDC meshwork and rare or absent LP cells outside
      the nodules. In angioimmunoblastic T-cell lymphoma (AITL), scattered regressed
      germinal centers are usually noted, although hyperplastic germinal centers are
      seen during the early stages of the disease (EAITL). Identifying the FDC
      meshwork, mainly in association with blood vessels, constitutes one of the most
      typical findings of the disease. In conclusion, the morphologic pattern of the
      FDC meshwork in early lymphomas of follicular origin is heterogenous and differs
      according to the lymphoma subtypes. These FDC patterns are recognizable in the
      most typical cases when the lymphoma is in its early stage and still maintains a
      follicular/nodular pattern of growth. The FDC patterns seen in the CD21 and CD23
      stains contribute to the recognition of early stages of lymphomas involving
      follicles. Conversely, tumor cell immunostains for BCL2, cyclin D1, and other
      stains form the basis for the definition of lymphoma subtypes. 

PMID- 24911252
TI  - Tissue biomarkers of prognostic significance in hepatocellular carcinoma.
AB  - Despite major advancements in the clinical management of hepatocellular carcinoma
      (HCC), the natural history of this disease is characterized by an invariably poor
      prognosis. However, there are significant interindividual variations in the
      biologic behavior of this tumor and this combined with the confounding effect of
      liver function on patient survival makes prognostic prediction particularly
      difficult. Several studies have attempted to investigate the prognostic role of
      tissue biomarkers to better understand the molecular basis of HCC progression.
      These studies have looked at several aspects of cancer biology including
      proliferative potential, invasive capacity, and angiogenic promotion utilizing
      different methodologies. The aim of this review is to summarize the role of
      tissue biomarkers in the prognostic prediction of HCC and to outline questions
      and strategies in the prognostic assessment of HCC. 

PMID- 24911253
TI  - Arginase-1 is a novel immunohistochemical marker of hepatocellular
      differentiation.
AB  - Arginase-1 is an enzyme that catalyzes the hydrolysis of arginine to ornithine
      and urea in the urea cycle. In normal tissues, arginase-1 is primarily expressed
      in hepatocytes. Recent investigations have reported that the vast majority of
      hepatocellular carcinomas express this marker, but it is found only rarely in
      nonhepatocellular tumors. Owing to its restricted expression in hepatocellular
      carcinomas, arginase-1 has proved to be a useful immunohistochemical marker for
      assisting in distinguishing between these tumors and other neoplasms with which
      they may be confused. 

PMID- 24911254
TI  - Selected case from the Arkadi M. Rywlin international pathology slide series:
      lymphangiomatosis of the spleen associated with ipsilateral abdominopelvic and
      lower extremity venolymphatic malformations: a case report and review of the
      literature.
AB  - Herein, we report a 26-year-old patient with lymphangiomatosis of the spleen
      associated with multiple lymphatic and venous malformations. This patient
      underwent excision of a large lymphatic malformation of the left abdominal wall
      during childhood. A venous malformation of her left lower limb was excised during
      adolescence. Additional lymphatic malformations were found in the soft tissue of
      her left thigh at the age of 20. During hospitalization for a huge vulvar
      hemangioma at the age of 26, she was incidentally found to have asymptomatic
      splenomegaly, for which she underwent splenectomy. Examination of the spleen
      revealed diffuse involvement by a lymphatic anomaly predominantly forming small
      cystic spaces. Lymphangiomatosis of the spleen is rare and is classically
      separated into an isolated or pure form and a generalized form when it is
      associated with involvement of other viscera and/or multiple soft-tissue planes.
      This patient was affected by a borderline form of splenic lymphangiomatosis with
      limited somatic involvement of the superficial soft tissues and blood vessels.
      Notably, all the additional vascular malformations in this patient were left
      sided, and at this time there was no additional involvement of internal organ. No
      hereditary or known syndrome was identified. 

PMID- 24911255
TI  - Desorption dynamics of heavy alkali metal atoms (Rb, Cs) off the surface of
      helium nanodroplets.
AB  - We present a combined ion imaging and density functional theory study of the
      dynamics of the desorption process of rubidium and cesium atoms off the surface
      of helium nanodroplets upon excitation of the perturbed 6s and 7s states,
      respectively. Both experimental and theoretical results are well represented by
      the pseudodiatomic model for effective masses of the helium droplet in the
      desorption reaction of meff/mHe ~ 10 (Rb) and 13 (Cs). Deviations from this model
      are found for Rb excited to the 6p state. Photoelectron spectra indicate that the
      dopant-droplet interaction induces relaxation into low-lying electronic states of
      the desorbed atoms in the course of the ejection process. 

PMID- 24911256
TI  - Effect of roughness geometry on wetting and dewetting of rough PDMS surfaces.
AB  - Rough PDMS surfaces comprising 3 MUm hemispherical bumps and cavities with
      pitches ranging from 4.5 to 96 MUm have been fabricated by photolithographic and
      molding techniques. Their wetting and dewetting behavior with water was studied
      as model for print surfaces used in additive manufacturing and printed
      electronics. A smooth PDMS surface was studied as control. For a given pitch,
      both bumpy and cavity surfaces exhibit similar static contact angles, which
      increase as the roughness ratio increases. Notably, the observed water contact
      angles are shown to be consistently larger than the calculated Wenzel angles,
      attributable to the pinning of the water droplets into the metastable wetting
      states. Optical microscopy reveals that the contact lines on both the bumpy and
      cavity surfaces are distorted by the microtextures, pinning at the lead edges of
      the bumps and cavities. Vibration of the sessile droplets on the smooth, bumpy,
      and cavity PDMS surfaces results in the same contact angle, from 110 degrees -124
      degrees  to ~91 degrees . The results suggest that all three surfaces have the
      same stable wetting states after vibration and that water droplets pin in the
      smooth area of the rough PDMS surfaces. This conclusion is supported by visual
      inspection of the contact lines before and after vibration. The importance of
      pinning location rather than surface energy on the contact angle is discussed.
      The dewetting of the water droplet was studied by examining the receding motion
      of the contact line by evaporating the sessile droplets of a very dilute
      rhodamine dye solution on these surfaces. The results reveal that the contact
      line is dragged by the bumps as it recedes, whereas dragging is not visible on
      the smooth and the cavity surfaces. The drag created by the bumps toward the
      wetting and dewetting process is also visible in the velocity-dependent advancing
      and receding contact angle experiments. 

PMID- 24911257
TI  - Emerging techniques in orthopedics: advances in neuromuscular electrical
      stimulation.
AB  - Neuromuscular electrical stimulation (NMES) is defined as the application of an
      electric current to neuromuscular tissue to elicit a muscle contraction. It is
      typically applied in a clinical setting to strengthen muscle, particularly the
      quadriceps femoris, through repetitive contractions. Most studies to date
      involving NMES have been conducted using conventional lead-wired, or "single
      path" devices, and while effective, these devices have inherent limitations
      around comfort and incomplete muscle recruitment. In a prospective, randomized,
      controlled, single-blind trial, investigators found that using a novel
      "Multipath" device was effective when combined with standard rehabilitation in
      accelerating recovery after anterior cruciate ligament reconstruction. Additional
      research is warranted to explore whether this effect also occurs after other
      types of knee surgery. 

PMID- 24911258
TI  - Demography-adjusted tests of neutrality based on genome-wide SNP data.
AB  - Tests of the neutral evolution hypothesis are usually built on the standard null
      model which assumes that mutations are neutral and the population size remains
      constant over time. However, it is unclear how such tests are affected if the
      last assumption is dropped. Here, we extend the unifying framework for tests
      based on the site frequency spectrum, introduced by Achaz and Ferretti, to
      populations of varying size. Key ingredients are the first two moments of the
      site frequency spectrum. We show how these moments can be computed analytically
      if a population has experienced two instantaneous size changes in the past. We
      apply our method to data from ten human populations gathered in the 1000 genomes
      project, estimate their demographies and define demography-adjusted versions of
      Tajima's D, Fay & Wu's H, and Zeng's E. Our results show that demography-adjusted
      test statistics facilitate the direct comparison between populations and that
      most of the differences among populations seen in the original unadjusted tests
      can be explained by their underlying demographies. Upon carrying out whole-genome
      screens for deviations from neutrality, we identify candidate regions of recent
      positive selection. We provide track files with values of the adjusted and
      unadjusted tests for upload to the UCSC genome browser. 

PMID- 24911259
TI  - Cesium distribution and phases in proxy experiments on the incineration of
      radioactively contaminated waste from the Fukushima area.
AB  - After the March 11, 2011 Tohoku earthquake and Fukushima I Nuclear Power Plant
      accident, incineration was initially adopted as an effective technique for the
      treatment of post-disaster wastes. Accordingly, considerable amounts of
      radioactively contaminated residues were immediately generated through
      incineration. The level of radioactivity associated with radiocesium in the
      incineration ash residues (bottom ash and fly ash) became significantly high
      (several thousand to 100,000 Bq/kg) as a result of this treatment. In order to
      understand the modes of occurrence of radiocesium, bottom ash products were
      synthesized through combusting of refuse-derived fuel (RDF) with stable Cs salts
      in a pilot incinerator. Microscopic and microanalytical (SEM-EDX) techniques were
      applied and the following Cs categories were identified: low and high
      concentrations in the matrix glass, low-level partitioning into some newly-formed
      silicate minerals, partitioning into metal-sulfide compounds, and occurring in
      newly-formed Cs-rich minerals. These categories that are essentially silicate
      bound are the most dominant forms in large and medium size bottom ash particles.
      It is expected that these achievements provide solutions to the immobilization of
      radiocesium in the incineration ash products contaminated by Fukushima nuclear
      accident. 

PMID- 24911260
TI  - Internet-based therapy for mild to moderate depression in Swedish primary care:
      short term results from the PRIM-NET randomized controlled trial.
AB  - Depression presents a serious condition for the individual and a major challenge
      to health care and society. Internet-based cognitive behavior therapy (ICBT) is a
      treatment option supported in several trials, but there is as yet a lack of
      effective studies of ICBT in "real world" primary care settings. We examined
      whether ICBT differed from treatment-as-usual (TAU) in reducing depressive
      symptoms after 3 months. TAU comprised of visits to general practitioner,
      registered nurse, antidepressant drugs, waiting list for, or psychotherapy, or
      combinations of these alternatives. Patients, aged >= 18 years, who tentatively
      met criteria for mild to moderate depression at 16 primary care centers in the
      south-western region of Sweden were recruited and then assessed in a diagnostic
      interview. A total of 90 patients were randomized to either TAU or ICBT. The ICBT
      treatment included interactive elements online, a workbook, a CD with mindfulness
      and acceptance exercises, and minimal therapist contact. The treatment period
      lasted for 12 weeks after which both groups were assessed. The main outcome
      measure was Beck Depression Inventory-II (BDI-II). Additional measures were
      Montgomery Asberg Depression Rating Scale - self rating version (MADRS-S) and
      Beck Anxiety Inventory (BAI). The analyses revealed no significant difference
      between the two groups at post treatment, neither on BDI-II, MADRS-S, nor BAI.
      Twenty patients (56%) in the ICBT treatment completed all seven modules. Our
      findings suggest that ICBT may be successfully delivered in primary care and that
      the effectiveness, after 3 months, is at par with TAU. 

PMID- 24911261
TI  - Exploring the roles of family members in women's decision to use postpartum
      healthcare services from the perspectives of women and health care providers.
AB  - Although the postpartum period is a significant time in a family's life, few
      studies have addressed the lack of continuity of care and service use during the
      postpartum period. The aim of this study was to explore the roles of family
      members in Jordanian women's decision to use postpartum health care services. An
      exploratory qualitative design was employed to elicit the perspectives of 24
      women and 30 health care providers through six focus groups discussions conducted
      in April 2006. Interviews were transcribed verbatim, translated to English, and
      analyzed using an inductive content analysis approach. In our study, three roles
      of family members influencing Jordanian women's decision to use postpartum health
      care services emerged: supporter role, opponent role, and active participant in
      care role. Findings supported the need for a family-centered approach when
      providing postpartum care to enhance positive family roles and limit negative
      ones to promote continuity of healthcare services use during the postpartum
      period. 

PMID- 24911262
TI  - A 10-year population based study of 'opt-out' HIV testing of tuberculosis
      patients in Alberta, Canada: national implications.
AB  - INTRODUCTION: Compliance with the recommendation that all tuberculosis (TB)
      patients be tested for human immunodeficiency virus (HIV) has not yet been
      achieved in Canada or globally. METHODS: The experience of "opt-out" HIV testing
      of TB patients in the Province of Alberta, Canada is described over a 10-year
      period, 2003-2012. Testing rates are reported before and after the introduction
      of the "opt-out" approach. Risk factors for HIV seropositivity are described and
      demographic, clinical and laboratory characteristics of TB patients who were
      newly diagnosed versus previously diagnosed with HIV are compared. Genotypic
      clusters, defined as groups of two or more cases whose isolates of Mycobacterium
      tuberculosis had identical DNA fingerprints over the 10-year period or within 2
      years of one another, were analyzed for their ability to predict HIV co
      infection. RESULTS: HIV testing rates were 26% before and 90% after the
      introduction of "opt-out" testing. During the "opt-out" testing years those <15
      or >64 years of age at diagnosis were less likely to have been tested. In those
      tested the prevalence of HIV was 5.6%. In the age group 15-64 years, risk factors
      for HIV were: age (35-64 years), Canadian-born Aboriginal or foreign-born sub
      Saharan African origin, and combined respiratory and non-respiratory disease.
      Compared to TB patients previously known to be HIV positive, TB patients newly
      discovered to be HIV positive had more advanced HIV disease (lower CD4 counts;
      higher viral loads) at diagnosis. Large cluster size was associated with
      Aboriginal ancestry. Cluster size predicted HIV co-infection in Aboriginal
      peoples when clusters included all cases reported over 10 years but not when
      clusters included cases reported within 2 years of one another. CONCLUSION: "Opt
      out" HIV testing of TB patients is effective and well received. Universal HIV
      testing of TB patients (>80% of patients tested) has immediate (patients) and
      longer-term (TB/HIV program planning) benefits.

PMID- 24911263
TI  - Total synthesis of (+/-)-4-demethylenglerin A.
AB  - Racemic 4-demethylenglerin A (1'), a simplified analog of the guaiane-type
      sesquiterpene englerin A (1), has been synthesized. The cyclic hydrocarbon core
      structure was built through modified Metz approach using epoxynitrile cyclization
      and direct Aldol reaction to prepare the precursor of RCM. The primary
      cytotoxicity test summarized that C4 methyl has marked impacts on the
      bioactivity. 

PMID- 24911264
TI  - Metabolic profiling of the tissue-specific responses in mussel Mytilus
      galloprovincialis towards Vibrio harveyi challenge.
AB  - Mussel Mytilus galloprovincialis is a marine aquaculture shellfish distributing
      widely along the coast in north China. In this work, we studied the differential
      metabolic responses induced by Vibrio harveyi in digestive gland and gill tissues
      from M. galloprovincialis using NMR-based metabolomics. The differential
      metabolic responses in the two tissue types were detected, except the similarly
      altered taurine and betaine. These metabolic responses suggested that V. harveyi
      mainly induced osmotic disruption and reduced energy demand via the metabolic
      pathways of glucose synthesis and ATP/AMP conversion in mussel digestive gland.
      In mussel gill tissues, V. harveyi basically caused osmotic stress and possible
      reduced energy demand as shown by the elevated phosphocholine that is involved in
      one of the metabolic pathways of ATP synthesis from ADP and phosphocholine. The
      altered mRNA expression levels of related genes (superoxide dismutase with copper
      and zinc, heat shock protein 90, defensin and lysozyme) suggested that V. harveyi
      induced clear oxidative and immune stresses in both digestive gland and gill
      tissues. However, the mRNA expression levels of both lysozyme and defensin in
      digestive gland were more significantly up-regulated than those in gill from V.
      harveyi-challenged mussel M. galloprovincialis, meaning that the immune organ,
      digestive gland, was more sensitive than gill. Overall, our results indicated
      that V. harveyi could induce tissue-specific metabolic responses in mussel M.
      galloprovincialis.

PMID- 24911265
TI  - Insulin-like growth factor-1 as a prognostic marker in patients with acute
      ischemic stroke.
AB  - OBJECTIVE: Insulin-like growth factor-1 (IGF-1) has been associated with
      cardiovascular risk factors and atherosclerosis. The aim of the present study was
      to evaluate the prognostic value of IGF-1 levels in patients with acute ischemic
      stroke (AIS). METHODS: All patients with first-ever AIS from August 1, 2012 to
      August 31, 2013 were recruited to participate in the study. Clinical data were
      collected. The National Institutes of Health Stroke Scale (NIHSS) score was
      assessed on admission blinded to serum IGF-1 levels. For the assessment of
      functional outcome at 90 days Modified Rankin Scale (mRS) was used. On admission,
      serum IGF-1 levels were determined by chemiluminescence immunoassay. The
      influence of IGF-1 levels on functional outcome and death was assessed by
      multivariate logistic regression analysis. RESULTS: Patients with an unfavorable
      outcomes and non-survivors had significantly decreased serum IGF-1 levels on
      admission (P<0.0001 for both). IGF-1 was an independent prognostic marker of
      functional outcome and death [odds ratio 0.89 (0.84-0.93) and 0.90 (0.84-0.95),
      respectively, P<0.0001 for both, adjusted for age, NIHSS score and other
      predictors] in patients with ischemic stroke. Serum IGF-1 levels <=130 ng/mL was
      as an value indicator for unfavorable functional outcome (OR 3.31, 95% CI:1.87
      5.62; P<0.0001), after adjusting for other significant confounders. CONCLUSIONS:
      We reported a significant association between low serum IGF-1 levels and
      unfavorable functional outcome and death.

PMID- 24911266
TI  - Geographic distance affects dispersal of the patchy distributed greater long
      tailed hamster (Tscherskia triton).
AB  - Dispersal is a fundamental process in ecology influencing the genetic structure
      and the viability of populations. Understanding how variable factors influence
      the dispersal of the population is becoming an important question in animal
      ecology. To date, geographic distance and geographic barriers are often
      considered as main factors impacting dispersal, but their effects are variable
      depending on different conditions. In general, geographic barriers affect more
      significantly than geographic distance on dispersal. In rapidly expanding
      populations, however, geographic barriers have less effect on dispersal than
      geographic distance. The effects of both geographic distance and geographic
      barriers in low-density populations with patchy distributions are poorly
      understood. By using a panel of 10 microsatellite loci we investigated the
      genetic structure of three patchy-distributed populations of the Greater long
      tailed hamster (Tscherskia triton) from Raoyang, Guan and Shunyi counties of the
      North China Plain. The results showed that (i) high genetic diversity and
      differentiation exist in three geographic populations with patchy distributions;
      (ii) gene flow occurs among these three populations with physical barriers of
      Beijing city and Hutuo River, which potentially restricted the dispersal of the
      animal; (iii) the gene flow is negatively correlated with the geographic
      distance, while the genetic distance shows the positive correlation. Our results
      suggest that the effect of the physical barriers is conditional-dependent,
      including barrier capacity or individual potentially dispersal ability.
      Geographic distance also acts as an important factor affecting dispersal for the
      patchy distributed geographic populations. So, gene flow is effective, even at
      relatively long distances, in balancing the effect of geographic barrier in this
      study. 

PMID- 24911267
TI  - Determination of rate constants and equilibrium constants for solution-phase drug
      protein interactions by ultrafast affinity extraction.
AB  - A method was created on the basis of ultrafast affinity extraction to determine
      both the dissociation rate constants and equilibrium constants for drug-protein
      interactions in solution. Human serum albumin (HSA), an important binding agent
      for many drugs in blood, was used as both a model soluble protein and as an
      immobilized binding agent in affinity microcolumns for the analysis of free drug
      fractions. Several drugs were examined that are known to bind to HSA. Various
      conditions to optimize in the use of ultrafast affinity extraction for
      equilibrium and kinetic studies were considered, and several approaches for these
      measurements were examined. The dissociation rate constants obtained for soluble
      HSA with each drug gave good agreement with previous rate constants reported for
      the same drugs or other solutes with comparable affinities for HSA. The
      equilibrium constants that were determined also showed good agreement with the
      literature. The results demonstrated that ultrafast affinity extraction could be
      used as a rapid approach to provide information on both the kinetics and
      thermodynamics of a drug-protein interaction in solution. This approach could be
      extended to other systems and should be valuable for high-throughput drug
      screening or biointeraction studies. 

PMID- 24911268
TI  - Selected phytotoxins and organic extracts from endophytic fungus Edenia
      gomezpompae as light reaction of photosynthesis inhibitors.
AB  - In a search for natural herbicides, we investigated the action mechanism of the
      naphthoquinone spiroketals, isolated from the endophytic fungus Edenia
      gomezpompae: preussomerins EG1 (1) and EG4 (2), and palmarumycins CP17 (3), and
      CP2 (4) on the photosynthesis light reactions. The naphthoquinone spiroketals 1-4
      inhibited the ATP synthesis in freshly lysed spinach thylakoids from water to MV,
      and they also inhibited the non-cyclic electron transport in the basal,
      phosphorylating and uncoupled conditions from water to MV. Therefore, they act as
      Hill reaction inhibitors. The results suggested that naphthoquinone spiroketals 1
      4 have two interactions and inhibition site on the PSII electron transport chain.
      The first one involves the water splitting enzyme inhibition; and, the second on
      the acceptor site of PSII in a similar way that herbicide Diuron, studied by
      polaroghaphy and corroborated by fluorescence of the chlorophyll a of PSII. The
      culture medium and mycelium organic extracts from four morphological variants of
      E. gomezpompae were phytotoxic, and the culture medium extracts were more potent
      than mycelium extracts. They also act as Hill reaction inhibitors. 

PMID- 24911269
TI  - Probing HSA-ionic liquid interactions by spectroscopic and molecular docking
      methods.
AB  - Herein, we report the interaction of synthesized pyrrolidinium based ionic
      liquid, N-butyl-N-methyl-2-oxopyrrolidinium bromide (BMOP) with human serum
      albumin (HSA). The BMOP was characterized by using (1)H NMR, (13)C NMR and FT-IR
      techniques. The critical micelle concentration (cmc) of BMOP was confirmed by
      surface tension, conductivity and contact angle measurements. The interactions
      between HSA and BMOP were studied by steady-state and time-resolved fluorescence,
      UV-visible, FT-IR spectroscopic and molecular docking methods. The steady-state
      fluorescence spectra showed that BMOP quenched the fluorescence of HSA through
      combined quenching mechanism. Corresponding thermodynamic parameters viz. Gibbs
      free energy change (DeltaG), entropy change (DeltaS) and enthalpy change (DeltaH)
      illustrated that the binding process was spontaneous and entropy driven. It is
      also suggested that hydrophobic forces play a key role in the binding of BMOP to
      HSA. In addition, the pyrene probe analysis again suggests the involvement of
      hydrophobic interaction in HSA-BMOP complex formation. Surface tension profile
      showed that the cmc value of BMOP in the presence of HSA is higher than the cmc
      value of pure BMOP. The FT-IR results show a conformational change in the
      secondary structure of HSA upon the addition of BMOP. The molecular docking
      result indicated that BMOP binds with HSA at hydrophobic pocket domain IIA with
      hydrophobic and hydrogen bond interactions in which hydrophobic interactions are
      dominating. 

PMID- 24911270
TI  - In vitro DNA binding studies of anticancer drug idarubicin using spectroscopic
      techniques.
AB  - The interaction between idarubicin and double stranded deoxyribonucleic acid (ds
      DNA) was investigated by UV-VIS spectrophotometry, fluorescence and Raman
      spectroscopy techniques. The absorption spectra of idarubicin with ds-DNA showed
      a slight red shift and hypochromic effect. In the fluorescence experiments,
      emission peaks were decreased by adding ds-DNA. Using ethidium bromide (ETB) as a
      fluorescence probe, fluorescence quenching of the emission peak was observed in
      the ETB-DNA system when idarubicin was added. Moreover, similar results were
      obtained in Raman spectroscopy. Binding constants of idarubicin with ds-DNA were
      determined as 5.14*10(5) M(-1) and 5.8*10(5) M(-1) for UV-VIS spectrophotometry
      and fluorescence spectroscopy, respectively. The large binding constant indicated
      that idarubicin has a high affinity with ds-DNA. All the evidences indicated that
      the binding mode of idarubicin with DNA was an intercalative binding.
      Furthermore, quantitative determination of idarubicin in pharmaceutical
      formulation was done.

PMID- 24911271
TI  - Photochemical and photobiological studies on furoquinazolines as new psoralen
      analogs.
AB  - Linear (L) and angular (A) 4',5'-dimethylfuroquinazolines (FQZs) were synthesized
      and studied as furocoumarin analogs. These molecules proved to be photounstable
      with a photodegradation extent correlated to UVA light doses. Both compounds did
      intercalate inside the DNA double helix, but were not able to photobind DNA bases
      under UVA irradiation. This behavior was further rationalized through docking
      studies. The photosensitizing effects of these compounds were evaluated on Jurkat
      tumor cells and NCTC-2544 human keratinocytes, with and without antioxidants, to
      demonstrate the involvement of a photodynamic mechanism. Indeed, significant
      amounts of singlet oxygen and superoxide anion were generated in the presence of
      both compounds, that account for the oxidative damage induced to some isolated
      biological substrates (DNA, amino acids, proteins and lipids). Photophysical
      studies by use of a flash photolysis set up showed detectable triplet population
      and production of singlet reactive oxygen species for linear furoquinazoline,
      which can be responsible for the oxidation of biological substrates, and
      therefore can affect the cell proliferation. 

PMID- 24911272
TI  - Synthesis of ZnO nanoparticles using the cell extract of the cyanobacterium,
      Anabaena strain L31 and its conjugation with UV-B absorbing compound shinorine.
AB  - In the present work, we describe a cheap, unexplored and simple procedure for the
      synthesis of zinc oxide nanoparticles (ZnONPs) using the cell extract of the
      cyanobacterium, Anabaena strain L31. An attempt was also made to conjugate
      synthesized ZnONPs with a UV-absorbing water soluble compound shinorine. UV-vis
      spectroscopy, X-ray diffraction (XRD), Fourier transform infra-red (FTIR)
      spectroscopy, transmission electron microscopy (TEM) and TEM-selected area
      electron diffraction (SAED) analyses were made to elucidate the formation and
      characterization of ZnONPs and ZnONPs-shinorine conjugate. The synthesized ZnONPs
      were characterized by a sharp peak at 370 nm in UV-vis spectrum. TEM images
      showed the formation of spherical shaped nanoparticles with an average size of 80
      nm. Results of selective area electron diffraction (SAED) pattern showed a set of
      rings which suggested uniform shape with hexagonal structure of ZnONPs. XRD
      spectra confirmed the crystalline structure of particles. Conjugation of ZnONPs
      with shinorine was successfully achieved at pH 7.0 and 10mM concentration of
      shinorine. The conjugate showed a zeta potential value of -3.75 mV as compared to
      +30.25 mV of ZnONPs. The change in zeta potential value of ZnONPs-shinorine
      conjugate was attributed to the changes in the surface functionalities after
      conjugation. The generation of in vivo reactive oxygen species (ROS) by Anabaena
      strain L31 with treatment of ZnONPs-shinorine conjugate showed approximately 75%
      less ROS generation as compared to ZnONPs. Properties exhibited by the ZnONPs
      shinorine conjugate suggest that it may be used as a potential agent in
      developing environmental-friendly sunscreen filters of biological origin.

PMID- 24911273
TI  - Ruthenium(III) S-methylisothiosemicarbazone Schiff base complexes bearing
      PPh3/AsPh3 coligand: synthesis, structure and biological investigations,
      including antioxidant, DNA and protein interaction, and in vitro anticancer
      activities.
AB  - New Ru(III) isothiosemicarbazone complexes [RuCl(EPh3)L(1-4)] (E=P or As) were
      obtained from the reactions between [RuCl3(EPh3)3] and bis(salicylaldehyde)-S
      methylisothiosemicarbazone (H2L(1-3))/bis(2-hydroxy-naphthaldehyde)-S
      methylisothiosemicarbazone (H2L(4)) ligands. The new complexes were characterized
      by using elemental analyses and various spectral (UV-Vis, IR, (1)H NMR, FAB-Mass
      and EPR) methods. The redox properties of the complexes were studied by using
      cyclic voltammetric method. The new complexes were subjected to various
      biological investigations such as antioxidant assays involving DPPH radical,
      hydroxyl radical, nitric oxide radical and hydrogen peroxide, DNA/protein
      interaction studies and in vitro cytotoxic studies against human breast cancer
      cell line (MCF-7). New complexes showed excellent free radicals scavenging
      ability and could bind with DNA via intercalation. Protein binding studies using
      fluorescence spectroscopy showed that the new complexes could bind strongly with
      bovine serum albumin (BSA). Photo cleavage experiments using DNA of E-coli
      bacterium exhibited the DNA cleavage ability of the complexes. Further, the in
      vitro anticancer activity studies on the new complexes against MCF-7 cell line
      exhibited the ability of Ru(III) isothiosemicarbazone complexes to suppress the
      development of malignant neoplastic disease cells.

PMID- 24911274
TI  - Turn on ESPT: novel salicylaldehyde based sensor for biological important
      fluoride sensing.
AB  - A novel and simple salicylaldehyde based anion fluorescent sensor 1 has been
      designed, which can selectively sense fluoride by 'turn on' excited-state
      intermolecular proton transfer (ESPT). The binding constant and the stoichiometry
      were obtained by non-linear least-square analysis of the titration curves. 

PMID- 24911275
TI  - Metformin associated with photodynamic therapy--a novel oncological direction.
AB  - The aim of our study was to assess the effect of the combined treatment of
      Metformin (Metf) and 5, 10, 15, 20-tetra-sulfophenyl-porphyrin (TSPP)-mediated
      photodynamic therapy (PDT) on an in vivo tumour model. Wistar male rats were
      divided in 6 groups: group 1, treated with TSPP; groups 2 and 4 treated with TSPP
      and Metf, respectively, and irradiated 24h thereafter; group 3 was treated with
      Metf and the last two groups received the combined treatment, Metf administered
      prior (group 5) or after (group 6) irradiation. 72 h from the start of the
      treatment, tumour tissue was sampled for the investigation of oxidative and
      nitrosative stress. The apoptotic rate, inducible nitric oxide synthase (iNOS)
      and cyclooxygenase (COX)-2 expressions and matrix metalloproteinases activities
      were also quantified. Malondialdehyde and glutathione levels were significantly
      elevated in the groups treated with combined therapy (p<0.05). Metf associated
      with TSPP-PDT reduced iNOS and COX-2 expressions and enhanced nitrotyrosine
      levels in both therapeutic regimens. Peroxynitrate formation and its cytotoxic
      effect on tumour cells were related to an elevated index of apoptosis and
      necrosis. Moreover, MMP-2 activity reached a minimum in the groups which received
      combined therapy. Our results confirmed that the association of Metf with PDT
      might prove a new and promising oncological approach.

PMID- 24911276
TI  - Effect of the relative optical air mass and the clearness index on solar
      erythemal UV irradiance.
AB  - This paper analyses the effects of the clearness index (Kt) and the relative
      optical air mass (mr) on erythemal UV irradiance (UVER). The UVER measurements
      were made in Valencia (Spain) from 6:00 am to 6:00 pm between June 2003 and
      December 2012 and (140,000 data points). Firstly, two models were used to
      calculate values for the erythemal ultraviolet irradiance clearness index
      (KtUVER) as a function of the global irradiance clearness index (Kt). Secondly, a
      potential regression model to measure the KtUVER as a function of the relative
      optical air mass was studied. The coefficients of this regression were evaluated
      for clear and cloudy days, as well as for days with high and low ozone levels.
      Thirdly, an analysis was made of the relationship between the two effects in the
      experimental database, with it being found that the highest degree of agreement,
      or the joint highest frequencies, are located in the optical mass range mr?[1.0,
      1.2] and the clearness index range of Kt?[0.8, 1.0]. This is useful for
      establishing the ranges of parameters where models are more efficient. Simple
      equations have been tested that can provide additional information for the
      engineering projects concerning thermal installations. Fourthly, a high
      dispersion of radiation data was observed for intermediate values of the
      clearness for UV and UVER.

PMID- 24911277
TI  - Photodynamic therapy mediated antiproliferative activity of some metal-doped ZnO
      nanoparticles in human liver adenocarcinoma HepG2 cells under UV irradiation.
AB  - Photodynamic therapy (PDT) is a promising new modality for the treatment of
      cancer through generation of reactive oxygen species (ROS). In this work, human
      liver adenocarcinoma cells HepG2 were treated with zinc oxide nanoparticles (ZnO
      NPs), metal-doped-ZnO-NPs: Fe-ZnO-NPs Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs,
      Silica-coated ZnO-NPs, titanium dioxide nanoparticles (TiO2-NPs), titanium
      dioxide nano-tubes (TiO2-NTs) and ZnO-NPs/TiO2-NTs nanocomposite under UV
      irradiation. Doxorubicin was used as a standard drug. The results demonstrated
      that the ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs showed
      cytotoxicity against HepG2 cells, with the median growth inhibitory
      concentrations (IC50) 42.60, 37.20, 45.10, 77.20 and 56.50 MUg/ml, respectively,
      as compared to doxorubicin (IC50: 20.10 MUg/ml). Treatment of the cancer cells
      with ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs resulted in a
      significant increase in the activity of SOD and the levels of H2O2 and NO than
      those of control, accompanied with a significant decrease in the activity of CAT
      and GSH-Px. Also, depletion of reduced GSH, total protein and nucleic acids
      levels was observed. In conclusion, metal-doped ZnO-NPs may induce
      antiproliferative effect on HepG2 cells under UV-irradiation due to generation of
      ROS. Therefore, they could be included in modern clinical trials after in vivo
      more investigations, using photodynamic therapy technique.

PMID- 24911278
TI  - Spray-deposition and photopolymerization of organic-inorganic thiol-ene resins
      for fabrication of superamphiphobic surfaces.
AB  - Superamphiphobic surfaces, exhibiting high contact angles and low contact angle
      hysteresis to both water and low surface tension liquids, have attracted a great
      deal attention in recent years because of the potential of these materials in
      practical applications such as liquid-resistant textiles, self-cleaning surfaces,
      and antifouling/anticorrosion coatings. In this work, we present a simple
      strategy for fabricating of superamphiphobic coatings based on
      photopolymerization of hybrid thiol-ene resins. Spray-deposition and UV
      photopolymerization of thiol-ene resins containing hydrophobic silica
      nanoparticles and perfluorinated thiols provide a multiscale topography and low
      energy surface that endows the surface with superamphiphobicity. The wettability
      and chemical composition of the surfaces were characterized by contact-angle
      goniometry and X-ray photoelectron spectroscopy, respectively. The hierarchical
      roughness features of the thiol-ene surfaces were investigated with field
      emission scanning electron microscopy. Droplet impact and sandpaper abrasion
      tests indicate the coatings respectively possess a robust antiwetting behavior
      and good mechanical durability. 

PMID- 24911279
TI  - Mixed T helper cell signatures in chronic rhinosinusitis with and without polyps.
AB  - In chronic rhinosinusitis (CRS) different phenotypes have been reported based on
      cytokine profile and inflammatory cell patterns. The aim of this study was to
      characterize the intracytoplasmatic cytokines of T cells infiltrating the
      inflamed sinonasal mucosa. METHODS: Infiltrated T cells and tissue homogenates
      from sinonasal mucosal samples of 7 healthy subjects, 9 patients with CRS without
      nasal polyp (CRSsNP), 15 with CRS with nasal polyps (CRSwNP) and 5 cystic
      fibrosis patients (CF-NP) were analyzed for cytokine expression using flow
      cytometry and multiplex analysis respectively. Intracytoplasmic cytokinesin T
      cells were analyzed after stimulation of nasal polyps with Staphylococcus aureus
      enterotoxin B for 24 hours. RESULTS: The number of T cells per total living cells
      was significantly higher in patients with CRSwNP vs. CRSsNP and controls. 85% of
      the CD4(+) T cells showed to be memory T cells. The effector T cells present in
      all tissues have a predominant Th1 phenotype. Only in CRSwNP, a significant
      fraction of T cells produced the Th2 cytokines IL-4 and IL-5, while nasal polyps
      from CF patients were characterized by a higher CD4/CD8 T cell ratio and an
      increased number of Th17 cells. 24 h stimulation with SEB resulted in a
      significant induction of CD4(+) T cells producing IL-10 (Tr1 cells). CONCLUSION:
      T cell cytokine patterns in healthy and inflamed sinonasal mucosa revealed that
      Th2 cells (IL-4 and IL-5 producing cells) are significantly increased in CRSwNP
      mucosal inflammation. Exposure to SEB stimulates Tr1 cells that may contribute to
      the Th2 bias in CRSwNP.

PMID- 24911280
TI  - A defective TLR4 signaling for IFN-beta expression is responsible for the
      innately lower ability of BALB/c macrophages to produce NO in response to LPS as
      compared to C57BL/6.
AB  - C57BL/6 mice macrophages innately produce higher levels of NO than BALB/c cells
      when stimulated with LPS. Here, we investigated the molecular events that account
      for this intrinsic differential production of NO. We found that the lower
      production of NO in BALB/c is not due to a subtraction of L-arginine by arginase,
      and correlates with a lower iNOS accumulation, which is independent of its
      degradation rate. Instead, the lower accumulation of iNOS is due to the lower
      levels of iNOS mRNA, previously shown to be also independent of its stability,
      suggesting that iNOS transcription is less efficient in BALB/c than in C57BL/6
      macrophages. Activation of NFkappaB is more efficient in BALB/c, thus not
      correlating with iNOS expression. Conversely, activation of STAT-1 does correlate
      with iNOS expression, being more prominent in C57BL/6 than in BALB/c macrophages.
      IFN-beta and IL-10 are more highly expressed in C57BL/6 than in BALB/c
      macrophages, and the opposite is true for TNF-alpha. Whereas IL-10 and TNF-alpha
      do not seem to participate in their differential production of NO, IFN-beta has a
      determinant role since 1) anti-IFN-beta neutralizing antibodies abolish STAT-1
      activation reducing NO production in C57BL/6 macrophages to levels as low as in
      BALB/c cells and 2) exogenous rIFN-beta confers to LPS-stimulated BALB/c
      macrophages the ability to phosphorylate STAT-1 and to produce NO as efficiently
      as C57BL/6 cells. We demonstrate, for the first time, that BALB/c macrophages are
      innately lower NO producers than C57BL/6 cells because they are defective in the
      TLR-4-induced IFN-beta-mediated STAT-1 activation pathway. 

PMID- 24911281
TI  - Quantitative characterization of cell behaviors through cell cycle progression
      via automated cell tracking.
AB  - Cell behaviors are reflections of intracellular tension dynamics and play
      important roles in many cellular processes. In this study, temporal variations in
      cell geometry and cell motion through cell cycle progression were quantitatively
      characterized via automated cell tracking for MCF-10A non-transformed breast
      cells, MCF-7 non-invasive breast cancer cells, and MDA-MB-231 highly metastatic
      breast cancer cells. A new cell segmentation method, which combines the threshold
      method and our modified edge based active contour method, was applied to optimize
      cell boundary detection for all cells in the field-of-view. An automated cell
      tracking program was implemented to conduct live cell tracking over 40 hours for
      the three cell lines. The cell boundary and location information was measured and
      aligned with cell cycle progression with constructed cell lineage trees. Cell
      behaviors were studied in terms of cell geometry and cell motion. For cell
      geometry, cell area and cell axis ratio were investigated. For cell motion,
      instantaneous migration speed, cell motion type, as well as cell motion range
      were analyzed. We applied a cell-based approach that allows us to examine and
      compare temporal variations of cell behavior along with cell cycle progression at
      a single cell level. Cell body geometry along with distribution of peripheral
      protrusion structures appears to be associated with cell motion features.
      Migration speed together with motion type and motion ranges are required to
      distinguish the three cell-lines examined. We found that cells dividing or
      overlapping vertically are unique features of cell malignancy for both MCF-7 and
      MDA-MB-231 cells, whereas abrupt changes in cell body geometry and cell motion
      during mitosis are unique to highly metastatic MDA-MB-231 cells. Taken together,
      our live cell tracking system serves as an invaluable tool to identify cell
      behaviors that are unique to malignant and/or highly metastatic breast cancer
      cells. 

PMID- 24911282
TI  - Identification and phylogenetic relationship of Iranian strains of various
      Leishmania species isolated from cutaneous and visceral cases of leishmaniasis
      based on N-acetylglucosamine-1-phosphate transferase gene.
AB  - The identity of Iranian Leishmania species has been resolved to some extent by
      some genetic markers. In this study, based on N-acetylglucosamine-1-phosphate
      transferase (nagt) gene, we further elucidated the identity and phylogeny of the
      prevalent species in this country. DNAs of 121 isolates belonging to cutaneous
      leishmaniasis (CL) patients, canine visceral leishmaniasis (CVL) cases, and
      Rhombomys opimus rodents were amplified by targeting a partial sequence of nagt
      gene. All the amplicons were analyzed with restriction fragment length
      polymorphism (RFLP) using Acc1 enzyme, and 49 amplicons representing different
      reservoir hosts were sequenced and aligned with similar sequences from GenBank
      database. The RFLP analysis revealed that 41 CL patients were infected Leishmania
      tropica and 36 with Leishmania major. Among 10 CVL isolates, 6 were identified as
      Leishmania infantum and 4 as L. tropica. Amongst 34 rodents' isolates, 11 and 23
      isolates exhibited patterns similar to those of L. major, and L.
      tropica/Leishmania turanica, respectively. The sequencing results from all CL
      patients, CVL cases, and 4 reservoir rodents were in agreement with RFLP analysis
      and showed 99-100% homologies with the registered species of L. major, L.
      tropica, and L. infantum from Turkey, Tunisia, Iraq and Israel. Of the 7 rodent
      isolates exhibiting RFLP patterns similar to L. tropica/L. turanica, 3 exhibited
      the highest homologies (99-100%) with L. turanica and 4 with Leishmania gerbilli.
      The 49 nagt DNA sequences were grouped into five clusters representing L. major,
      L. tropica, L. infantum, L. turanica and L. gerbilli species, encompassing 19
      haplotypes. No correlation was observed between intraspecies divergence and
      geographic distribution of haplotypes. The L. tropica haplotypes exhibited more
      homologies with those of L. infantum than L. major (97.2% vs. 96.9%), a probable
      indication to the potential ability of L. tropica to visceralize.
      Characterization of Iranian Leishmania isolates using nagt gene allowed
      unambiguous identification of five prevalent species with a high-resolution
      phylogeny. 

PMID- 24911283
TI  - DNA sequence polymorphisms of the pfmdr1 gene and association of mutations with
      the pfcrt gene in Indian Plasmodium falciparum isolates.
AB  - Mutations in the Plasmodium falciparum multidrug resistance (pfmdr1) gene are
      known to provide compensatory fitness benefits to the chloroquine (CQ)-resistant
      malaria parasites and are often associated with specific mutations in the P.
      falciparum CQ resistant transporter (pfcrt) gene. Prevalence of the specific
      mutations in these two genes across different malaria endemic regions was mostly
      studies. However, reports on mutations in the pfmdr1 gene and their genetic
      associations with mutations in the pfcrt gene in Indian P. falciparum field
      isolates are scarce. We have sequenced a 560 bp region of pfmdr1 coding sequence
      in 64 P. falciparum isolates collected from different malaria endemic populations
      in India. Twenty out of these 64 isolates were laboratory cultured with known in
      vitro CQ sensitiveness (10 sensitive and 10 resistant). Three low frequency
      mutations (two non-synonymous and one synonymous) in the pfmdr1 gene were
      segregating in Indian isolates in addition to the predominant Y86 and Y184 ones,
      with high haplotype and nucleotide diversity in the field isolates in comparison
      to the cultured ones. No statistically significant genetic association between
      the mutations in the pfmdr1 and pfcrt gene could be detected; almost all observed
      associations were intragenic in nature. The results on the genetic diversity of
      the pfmdr1 gene were discussed in term of evolutionary perspectives in Indian P.
      falciparum, with possible future potential of gaining further insights on this
      gene in view of evolving malaria parasites resistant to artemisinin partner
      drugs.

PMID- 24911285
TI  - Photoelectrodes based upon Mo:BiVO4 inverse opals for photoelectrochemical water
      splitting.
AB  - BiVO4 has been regarded as a promising material for photoelectrochemical water
      splitting, but it suffers from a major challenge on charge collection and
      utilization. In order to meet this challenge, we design a nanoengineered three
      dimensional (3D) ordered macro-mesoporous architecture (a kind of inverse opal)
      of Mo:BiVO4 through a controllable colloidal crystal template method with the
      help of a sandwich solution infiltration method and adjustable post-heating time.
      Within expectation, a superior photocurrent density is achieved in return for
      this design. This enhancement originates primarily from effective charge
      collection and utilization according to the analysis of electrochemical impedance
      spectroscopy and so on. All the results highlight the great significance of the
      3D ordered macro-mesoporous architecture as a promising photoelectrode model for
      the application in solar conversion. The cooperating amplification effects of
      nanoengineering from composition regulation and morphology innovation are helpful
      for creating more purpose-designed photoelectrodes with highly efficient
      performance. 

PMID- 24911284
TI  - Molecular epidemiology and evolution of A(H1N1)pdm09 and H3N2 virus during winter
      2012-2013 in Beijing, China.
AB  - In order to evaluate the epidemiology of influenza A and its surface antigens
      (haemagglutinin [HA] and neuraminidase [NA]) for molecular epidemiology and
      evolution analysis during winter 2012-2013 in Beijing, China, we worked within
      the framework of the Chinese National Influenza Center and collected nasal swabs
      of patients presenting with influenza-like illness. We found that both
      A(H1N1)pdm09 (46.8%) and H3N2 (53.2%) viruses were the predominant strains during
      the 2012-2013 influenza epidemic. The peak phase started at the second week of
      2013 and lasted about 1month. We obtained HA and NA sequences of viruses from 44
      patients by using Sanger sequencing. None of the strains had the oseltamivir
      resistance site H274Y. Phylogenetic analysis of 29 A(H1N1)pdm09 viruses showed a
      genetic drift from the vaccine strain A/California/07/2009 with mutations
      (H155Q/R and L178I) at the antigenic sites Ca and Sa of HA; the strains were
      classified into genetic groups 6 and 7 because of the presence of D114N, S160G,
      S202T, and A214T mutations in HA. H3N2 viruses formed seasonal phylogenetic
      clusters representative for each season from 2000 to 2013; 15 of the 2012-2013
      H3N2 strains were assigned to the A/Victoria/361/2011 genetic clade with
      mutations at the antigenic sites A, B and C of HA, including R158K/G, N161S,
      Q172H, and N294K; the 2012-2013 strains with V239I, S61N, T64I, and A214S HA
      mutations were classified into subgroup 3C. The mutation of potential N-linked
      glycosylation residues at the antigenic sites of HA and around the enzymatic
      active center of NA may have increased viral pathogenicity by masking antigenic
      sites from immune recognition. Our data suggest that influenza vaccines are
      generally effective, but still provide suboptimal protection due to antigenic
      variation. This study increases the understanding of influenza A viruses in
      humans and is informative for future vaccine strain selection. 

PMID- 24911286
TI  - Polybrominated diphenyl ethers, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), and
      p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentrations in sera collected
      in 2009 from Texas children.
AB  - Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and p,p'
      dichlorodiphenyldichloroethylene (p,p'-DDE) have been measured in surplus serum
      collected in 2009 from a convenience sample of 300 Texas children (boys and
      girls) in the birth to 13 years of age range. Serum concentrations of traditional
      persistent organic pollutants such as 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153)
      and p,p'-DDE did not change consistently with age. By contrast, serum
      concentrations of tetra-, penta-, and hexa-BDEs were lowest in the youngest
      children (birth to two year old) and increased 3.0 to 7.9 times, depending on the
      analyte, for children in the >4 to 6 years of age group. From the apex
      concentration to the 10 to 13 years of age group, concentrations decreased
      significantly except for 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE-153), which
      also had a longer apex concentration of >4 to 8 years of age. This concentration
      trend for PBDE-153 is most likely due to a longer half-life of PBDE-153 than of
      other PBDE congeners. The observed PBDEs concentration patterns by age may be
      related, at least in part, to ingestion of residential dust containing PBDEs
      through hand-to-mouth behavior among toddlers, preschoolers, and kindergarteners.
      Further studies to characterize young children's exposure to PBDEs are warranted
      and, in particular, to determine the lifestyle factors that may contribute to
      such exposures. 

PMID- 24911288
TI  - How joint torques affect hamstring injury risk in sprinting swing-stance
      transition.
AB  - PURPOSE: The potential mechanisms of hamstring strain injuries in athletes are
      not well understood. The study, therefore, was aimed at understanding hamstring
      mechanics by studying loading conditions during maximum-effort overground
      sprinting. METHODS: Three-dimensional kinematics and ground reaction force data
      were collected from eight elite male sprinters sprinting at their maximum effort.
      Maximal isometric torques of the hip and knee were also collected. Data from the
      sprinting gait cycle were analyzed via an intersegmental dynamics approach, and
      the different joint torque components were calculated. RESULTS: During the
      initial stance phase, the ground reaction force passed anteriorly to the knee and
      hip, producing an extension torque at the knee and a flexion torque at the hip
      joint. Thus, the active muscle torque functioned to produce flexion torque at the
      knee and extension torque at the hip. The maximal muscle torque at the knee joint
      was 1.4 times the maximal isometric knee flexion torque. During the late swing
      phase, the muscle torque counterbalanced the motion-dependent torque and acted to
      flex the knee joint and extend the hip joint. The loading conditions on the
      hamstring muscles were similar to those of the initial stance phase. CONCLUSIONS:
      During both the initial stance and late swing phases, the large passive torques
      at both the knee and hip joints acted to lengthen the hamstring muscles. The
      active muscle torques generated mainly by the hamstrings functioned to counteract
      those passive effects. As a result, during sprinting or high-speed locomotion,
      the hamstring muscles may be more susceptible to high risk of strain injury
      during these two phases.

PMID- 24911289
TI  - Are dinucleoside monophosphates relevant models for the study of DNA intrastrand
      cross-link lesions? The example of g[8-5m]T.
AB  - Oxidatively generated tandem lesions such as G[8-5m]T pose a potent threat to
      genome integrity. Direct experimental studies of the kinetics and thermodynamics
      of a specific lesion within DNA are very challenging, mostly due to the variety
      of products that can be formed in oxidative conditions. Dinucleoside
      monophosphates (DM) involving only the reactive nucleobases in water represent
      appealing alternative models on which most physical chemistry and structural
      techniques can be applied. However, it is not yet clear how relevant these models
      are. Here, we present QM/MM MD simulations of the cyclization step involved in
      the formation of G[8-5m]T from the guanine-thymine (GpT) DM in water, with the
      aim of comparing our results to our previous investigation of the same reaction
      in DNA ( Garrec , J. , Patel , C. , Rothlisberger , U. , and Dumont , E. ( 2012 )
      J. Am. Chem. Soc. 134 , 2111 - 2119 ). We show that, despite the different levels
      of preorganization of the two systems, the corresponding reactions share many
      energetic and structural characteristics. The main difference lies in the angle
      between the G and T bases, which is slightly higher in the transition state (TS)
      and product of the reaction in water than in the reaction in DNA. This effect is
      due to the Watson-Crick H-bonds, which are absent in the {GpT+water} system and
      restrain the relative positioning of the reactive nucleobases in DNA. However,
      since the lesion is accommodated easily in the DNA macromolecule, the induced
      energetic penalty is relatively small. The high similarity between the two
      reactions strongly supports the use of GpT in water as a model of the
      corresponding reaction in DNA. 

PMID- 24911290
TI  - Short chain polyethylene glycols unusually assist thermal unfolding of human
      serum albumin.
AB  - In the present study we have investigated the thermal stability of the globular
      transport protein human serum albumin (HSA), in the presence of two small chain
      polyethylene glycols (namely PEG 200 and PEG 400). Both near- and far-UV circular
      dichroism (CD) study reveal that addition of PEG moderately increases the alpha
      helical content of the protein without abruptly changing its tertiary structure.
      The hydration structure at the protein surface experiences a notable change at
      30% PEG (v/v) concentration as evidenced from compressibility and dynamic light
      scattering (DLS) measurements. Thermal denaturation of HSA in the presence of PEG
      has been studied by CD and fluorescence spectroscopy using the intrinsic
      fluorophore tryptophan and it has been found that addition of PEG makes the
      protein more prone towards unfolding, which is in contrary to what has been
      observed in case of larger molecular weight polymers. The energetics of the
      thermal unfolding process has been obtained using differential scanning
      calorimetry (DSC) measurements. Our study concludes that both the indirect
      excluded volume principle as well as interaction of the polymer at the protein
      surface is responsible for the observed change of the unfolding process. 

PMID- 24911291
TI  - Assessing value in biomedical research: the PQRST of appraisal and reward.

PMID- 24911292
TI  - Intratracheal instillation of single-wall carbon nanotubes in the rat lung
      induces time-dependent changes in gene expression.
AB  - The use of carbon nanotubes in the industry has grown; however, little is known
      about their toxicological mechanism of action. Single-wall carbon nanotube
      (SWCNT) suspensions were administered by single intratracheal instillation in
      rats. Persistence of alveolar macrophage-containing granuloma was observed around
      the sites of SWCNT aggregation at 90 days post-instillation in 0.2-mg- or 0.4-mg
      injected doses per rat. Meanwhile, gene expression profiling revealed that a
      large number of genes involved in the inflammatory response were markedly
      upregulated until 90 days or 180 days post-instillation. Subsequently, gene
      expression patterns were dramatically altered at 365 days post-instillation, and
      the number of upregulated genes involved in the inflammatory response was
      reduced. These results suggested that alveolar macrophage-containing granuloma
      reflected a characteristic of the histopathological transition period from the
      acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute
      phase response persistence up to 90 or 180 days after intratracheal instillation
      in this experimental setting. The expression levels of the genes Ctsk, Gcgr,
      Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were
      persistently upregulated in a dose-dependent manner until 365 days post
      instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12
      and Rnase9 were significantly upregulated until 754 days post-instillation. We
      propose that these persistently upregulated genes in the chronic-phase response
      following the acute-phase response act as potential biomarkers in lung tissue
      after SWCNT instillation. This study provides further insight into the time
      dependent changes in genomic expression associated with the pulmonary toxicity of
      SWCNTs.

PMID- 24911294
TI  - Today's family medicine clerkship.

PMID- 24911293
TI  - Superoxide production by cytochrome bc1 complex: a mathematical model.
AB  - Reactive oxygen species (ROS) are involved in the pathophysiology of several
      diseases (e.g. Alzheimer or atherosclerosis) and also in the aging process. The
      main source of ROS in aerobic organisms is the electron transport chain (ETC) in
      the inner mitochondrial membrane. Superoxide is produced at complexes I and III
      of the ETC, starting a complex network of ROS reactions. To achieve a deeper
      mechanistic understanding of how ROS are generated by complex III, we developed a
      mathematical model that successfully describes experimental data of complex III
      activity in various rat tissues, the production of ROS with and without antimycin
      and ROS generation depending on different values of the membrane potential ?Psi.
      The model also reinforces the idea of ubiquinone acting as a redox mediator
      between heme bL and oxygen, as proposed earlier. 

PMID- 24911295
TI  - Exploring interprofessional education in the family medicine clerkship: a CERA
      study.
AB  - BACKGROUND AND OBJECTIVES: The need for interprofessional education (IPE) to
      improve teamwork skills has been recognized by several national organizations.
      The purpose of this study was to investigate IPE integration in family medicine
      clerkships and factors associated with IPE's success. METHODS: A survey of
      clerkship directors at US allopathic medical schools was conducted through the
      Council of Academic Famiily Medicine Educational Research Alliance (CERA).
      Respondents were asked (1) whether IPE was part of the curriculum, (2) the
      educational methods used, (3) which health professions students and faculty
      participated in IPE, (4) what outcomes were measured, (5) the types of faculty
      development provided, and (6) the barriers encountered when implementing IPE.
      RESULTS: The response rate was 66% (88/134), and 38% reported incorporating IPE
      into the clerkship with most offering IPE in clinical activities. A wide variety
      of health professions students and faculty participated in clerkship IPE
      activities. One third of the respondents offered faculty development. Most agreed
      that third party funding (85%), IPE team training (94%), clearly defined roles
      (94%), and dedicated time during clinical care for team meetings (93%) were vital
      for IPE to succeed. Many programs did not measure IPE-specific outcomes (49%).
      Eighty percent reported at least one barrier to implementing IPE. The most common
      barriers were scheduling conflicts (46%) and lack of IPE experience (40%). No one
      reported a lack of institutional support for IPE. CONCLUSIONS: Few clerkships
      offered IPE. However, family medicine is in a unique position to highlight the
      value of interprofessional teamwork for students and should recognize and promote
      IPE opportunities.

PMID- 24911296
TI  - Practice-based learning and improvement in family medicine student clerkships: a
      CERA study.
AB  - BACKGROUND: Practice-based learning and improvement (PBLI) has been promoted as a
      key component of competency-based training in medical student education, but
      little is known about its implementation. METHODS: This project is part of a
      larger CERA omnibus survey of family medicine medical student clerkship directors
      carried out from July to September 2012. Analyses were conducted to assess
      clerkship infrastructure, learner assessment and feedback, and clerkship director
      perceptions of PBLI curricula. RESULTS: The majority (69.0%, 58/82) of family
      medicine clerkship directors reported that PBLI is not included in their
      clerkship. Significant predictors of PBLI in the curriculum include: regularly
      scheduled centralized teaching (weekly or more versus less than weekly, OR=1.14,
      95% CI=1.01--1.29) and clerkship director belief that students should achieve
      PBLI competency (agree in competency versus disagree in competency, OR=1.19, 95%
      CI=1.08--1.30). Few (20.5%, 16/78) family medicine clerkship directors reported
      that the amount of PBLI in their curriculum is likely to increase in the next 12
      months. The duration of the clerkship was a significant predictor of reported
      likelihood of increasing PBLI over the next 12 months (3 weeks versus 8 weeks,
      OR=1.23, 95% CI=1.00--1.51). CONCLUSIONS: Despite increased emphasis on quality
      improvement activities in practice, most family medicine clerkships do not
      currently offer PBLI curricula. Additionally, less than one in four family
      medicine clerkships plan on increasing the amount of PBLI curricula in the next
      12 months. Continued research in this area is needed to identify successful
      models for PBLI curricular offerings.

PMID- 24911297
TI  - STFM's National Clerkship Curriculum: CERA reveals impact, clerkship director
      needs.
AB  - BACKGROUND AND OBJECTIVES: Consistency is needed in family medicine clerkships
      nationwide. The Society of Teachers of Family Medicine's (STFM) National
      Clerkship Curriculum (NCC) and supporting NCC website have been developed to
      address this need. A survey was used to measure these tools' effect and guide
      future improvements. METHODS: The Council of Academic Family Medicine's (CAFM)
      Educational Research Alliance (CERA) 2012 survey of clerkship directors (CD) was
      used to answer two research questions: (1) To what extent are clerkships teaching
      the minimum core curriculum? and (2) What resources do clerkship directors
      identify as important in their role? RESULTS: The survey response rate was 66%
      (88/134). Ninety-two percent of these CDs are aware of the NCC, 74% report having
      visited the NCC website, and 71% plan to visit it more than once per year in the
      future. A total of 21.6% strongly agree that their clerkship content matches the
      NCC. CDs rate the quality of materials on the website as high and place greatest
      value on materials that can be downloaded and adapted to their clerkships.
      CONCLUSIONS: STFM's NCC website and materials are familiar to CDs although only
      one in five state their clerkship curriculum matches the NCC minimum core
      curriculum. The NCC editorial board needs to better understand why so few teach
      curriculum that closely matches the minimum core. Continued outreach to CDs can
      answer this question and improve our ability to support CDs as they incorporate
      the NCC into family medicine clerkships.

PMID- 24911298
TI  - A new clinical skills clerkship for medical students.
AB  - BACKGROUND AND OBJECTIVES: The transition to clinical clerkships can be
      challenging for medical students. In the context of a formal clinical curriculum
      redesign, a curriculum team led by family physicians systematically planned and
      implemented a 3-week course to prepare new third-year students for specialty
      specific clerkships. METHODS: Informed by a formal needs assessment, we developed
      a classroom-based Clinical Skills Clerkship (CSC) with varied instructional
      approaches. The three major curriculum components are (1) specialty-specific,
      longitudinal clinical care of a three-generation virtual family that is taught in
      lectures and small groups and assessed with an objective structured clinical
      examination (OSCE), (2) clinical skills including procedure stations and
      interprofessional education experiences, and (3) a series of professional
      development activities. The CSC has 90 hours of curriculum taught by more than
      120 faculty members from a wide variety of specialties and disciplines. A cohort
      of senior medical students teach in the course as part of a medical education
      elective. RESULTS: The CSC was first delivered to 98 students in 2012 who
      performed well on the course's OSCE. Quantitative and qualitative evaluations of
      both the curriculum components and the senior medical student teachers were
      positive. Performance on comparable CSC and Internal Medicine Clerkship OSCE
      stations and a series of student focus groups demonstrate longer-term impact.
      CONCLUSIONS: A successful curriculum redesign requires considerable planning and
      coordination. We designed and implemented a comprehensive CSC that was both well
      received and effective. Peer teaching programs can provide medical education
      leadership experiences with benefits for learners, teachers, and medical
      educators.

PMID- 24911299
TI  - Impact of a patient-centered medical home clerkship curriculum.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the impact of
      a patient-centered medical home (PCMH) curriculum introduced in a family medicine
      clerkship in 2011--2012. This new curriculum introduced third-year students to
      the PCMH using a variety of interactive educational formats, including case
      based, online, and experiential PCMH activities. METHODS: Qualitative analysis of
      student reflection essays explored themes based on PCMH experiences during family
      medicine clerkships. RESULTS: Pre-curricular needs assessment revealed an
      important gap in students' exposure to and knowledge of PCMH concepts consistent
      with existing literature. Qualitative thematic analysis examined students'
      perceptions of patient experiences in PCMH practices but also revealed rich,
      unprompted, and very positive perceptions of student and provider roles and
      system-based changes in the PCMH model. Only 2.3% of coded references (n=10, out
      of 435) described "negative" emotional reactions to PCMH experiences. More than
      half of student essays described important changes in self-assessed knowledge,
      skills, and attitudes, another significant and unexpected result. CONCLUSIONS:
      Successful implementation of innovative PCMH curricula is key to preparing a
      workforce ready to practice in a new model of health care delivery. This
      qualitative study demonstrates that an experiential PCMH curriculum can enhance
      third-year medical student self-assessed knowledge of and attitudes toward the
      PCMH and may improve perceptions of a career in primary care.

PMID- 24911300
TI  - Beta-blockers and depression in elderly hypertension patients in primary care.
AB  - BACKGROUND AND OBJECTIVES: Previous findings regarding a possible association
      between beta-blocker use and depression are mixed. To our knowledge there have
      been no studies investigating the association of beta-blockers with depression in
      primary care hypertension patients without previous myocardial infarction. The
      aim of this study was to determine the relation between lipophilic beta-blocker
      use and depression in elderly primary care patients with hypertension. METHODS:
      This was a cross-sectional study in primary care practices located in the South
      of The Netherlands. Primary care hypertension patients without previous
      myocardial infarction or heart failure (n=573), aged between 60 and 85 years
      (mean age=70+/-6.6), were included. All patients underwent a structured interview
      that included a self-report questionnaire to assess depression (PHQ-9), which was
      divided in four groups (PHQ-9 score of 0, 1--3, 4--8, 9 or higher). RESULTS: A
      PHQ-9 score of 0 was more prevalent in non-beta-blocker users versus lipophilic
      beta-blocker users (46% versus 35%), a PHQ-9 score of 4--8 was less prevalent in
      non-beta-blocker users as compared with lipophilic beta-blocker users (14% versus
      25%). A chi-squared test showed that lipophilic beta-blocker users as compared to
      non-beta-blockers users were more likely to be in a higher depression category.
      Ordinal regression showed a significant relationship between use of lipophilic
      beta-blockers and depression (OR=1.60, 95% CI=1.08--2.36) when adjusting for
      potential confounders. CONCLUSIONS: Our findings show that primary care
      hypertension patients who use a lipophilic beta-blocker are more likely to have
      higher depression scores than those who do not use a lipophilic beta-blocker.

PMID- 24911301
TI  - Needing a nudge: the effect of encouragement on submission rates and journal
      selection.
AB  - BACKGROUND AND OBJECTIVES: Mentorship within academic institutions influences
      research productivity; no published studies have addressed whether encouragement
      on a national level would have similar effects. We studied whether contact by a
      journal's editorial board members would affect submission rates or journal
      selection by authors. METHODS: Authors of potentially publishable conference
      materials presented at national conferences sponsored by the Society of Teachers
      of Family Medicine were randomized to receive an invitation to submit work to
      Family Medicine or to receive no contact. After 2 years, we surveyed authors
      regarding whether a manuscript had been attempted and, if completed, where it had
      been submitted and eventually published. RESULTS: A total of 345 submissions were
      reviewed, 72 met inclusion criteria, and 41 authors responded to the survey
      (57%). There were no differences in demographics, scholarly activity in general,
      or faculty status between study groups. There was no significant difference in
      whether manuscripts based on targeted projects had been written, completed,
      submitted, or published. There was a significant difference in where manuscripts
      were submitted with the inviting journal receiving proportionately more
      submissions from the group of authors that had been contacted (90% Contacted
      group, 43% No-Contact). CONCLUSIONS: Simple encouragement from editorial board
      members of a national peer-reviewed journal in the form of a single e-mail
      invitation did not increase the scholarly production of authors. Encouragement
      may, however, increase the likelihood that completed works are submitted to the
      inviting journal, which is a useful finding for journals interested in soliciting
      scholarly works of interest.

PMID- 24911302
TI  - A medical student leadership course led to teamwork, advocacy, and mindfulness.
AB  - BACKGROUND AND OBJECTIVES: Many medical trainees seek work among underserved
      communities but may be unprepared to cope with the challenges. Relationship
      centered qualities have been shown to promote physician resilience and prevent
      burnout. The UCLA-PRIME program aims to prepare medical students to work among
      vulnerable groups and begins with a 3-week leadership course. We describe this
      course and share lessons with those seeking to foster leadership, advocacy, and
      resiliency in our future physician workforce. METHODS: Twenty students
      participated in our curriculum that emphasized five competencies: leadership,
      advocacy, teamwork, mindfulness, and self-care. Course activities complemented
      the students' work as they developed a community outreach project. They assessed
      and reflected on their leadership, relationship, and team behaviors, were coached
      to improve these, learned mindfulness meditation, and participated in community
      forums. Our evaluation assessed course quality, project completion, leadership,
      mindfulness, and team relational coordination. RESULTS: Students were very
      satisfied with all aspects of the course. They designed a medical student
      elective addressing the health challenges of an incarcerated and formerly
      incarcerated population. While we found no change in leadership practices scores,
      students had high team relational coordination scores and improved mindfulness
      scores upon course completion. DISCUSSION: Our course to develop medical students
      as resilient leaders, team members, and advocates for medically underserved
      groups consisted of a community-based service project, coupled with a facilitated
      relationship-centered curriculum. It promoted qualities in students that
      characterize effective and resilient physician leaders; they were more mindful,
      related to each other effectively, and coordinated their activities well with one
      another.

PMID- 24911303
TI  - Resident duty hour changes: impact in the patient-centered medical home.
AB  - BACKGROUND AND OBJECTIVES: Family medicine residency programs are challenged with
      balancing hospital-based training with a longitudinal primary care continuity
      experience. In response to the Preparing the Personal Physician for Practice (P4)
      Initiative, the University of Missouri (MU) Family Medicine Residency Program
      sought to increase the presence of its residents in their continuity clinic, ie,
      the patient-centered medical home (PCMH). While initially successful, these
      efforts encountered formidable barriers with the July 2011 duty hour regulations
      from the Accreditation Council for Graduate Medical Education (ACGME). METHODS:
      PCMH hours and visit numbers were collected and analyzed for MU residents from
      July 2005 through June 2012. RESULTS: Comparing the 2 years before the P4
      schedule changes to the first 3 years after the P4 changes, MU first-year
      residents experienced a 27% increase in patient visits with a 13% increase in
      hours. In the subsequent 2 years, which incorporated compliance with the new
      ACGME regulations, first-year residents experienced a 33% decrease in visits with
      a 25% decrease in hours. This negated the increases seen with the previous P4
      schedule changes, and residents in all years of training experienced less visits,
      less hours, and less visits per hour. CONCLUSIONS: New duty hour regulations not
      only limit the time resident physicians spend in the hospital but also their
      experience in the ambulatory setting. Considering the emphasis family medicine
      training programs place on continuity of care and the PCMH, the new regulations
      will have significant implications for these programs.

PMID- 24911304
TI  - Increasing family medicine scholarly presentations and the incidence of duplicate
      research abstracts.
AB  - BACKGROUND AND OBJECTIVES: Scholarly activity in the form of original research
      presentations is valuable to the discipline of family medicine. Two major venues
      for family medicine researchers to present their work are the Society of Teachers
      of Family Medicine (STFM) Annual Spring Conference and the North American Primary
      Care Research Group (NAPCRG) Annual Meeting. Both of these organizations have
      seen increasing numbers of submissions and subsequent presentations in recent
      years. The purpose of this project was to analyze the trend in increasing
      presentations and document the incidence of duplicate research presentations
      across these two meetings. METHODS: Numbers of primary authors and coauthors were
      assessed and compared across meetings from 2009 to 2012. Abstracts from the same
      author(s) presenting at consecutive meetings were compared for originality.
      RESULTS: STFM has had a nearly 50% increase in numbers of presentations from 2009
      to 2012, and NAPCRG has seen a 17.6% increase. There has been an 88.2% increase
      in the number of presentation authors and coauthors who present at consecutive
      meetings during the same time frame. Four duplicate research presentations were
      found from 2009 through spring of 2012. CONCLUSIONS: Numbers of author and
      coauthor presenters at STFM and NAPCRG annual meetings have increased greatly
      since 2009. Very little duplication of research presentations was found. It
      appears that, for the most part, presenters at both STFM and NAPCRG are not
      presenting duplicate research projects. This is even more important now with
      limited space at meetings due to record numbers of presentations.

PMID- 24911305
TI  - Family physicians' suggestions to improve the documentation, coding, and billing
      system: a study from the residency research network of Texas.
AB  - BACKGROUND AND OBJECTIVES: The study's aim was to ascertain family physicians'
      suggestions on how to improve the commonly used US evaluation and management
      (E/M) rules for primary care. METHODS: A companion paper published in Family
      Medicine's May 2014 journal describes our study methods (Fam Med 2014;46(5):378
      84). RESULTS: Study subjects supported preserving the overall SOAP note
      structure. They especially suggested eliminating bullet counting in the E/M
      rules. For payment reform, respondents stated that brief or simple work should be
      paid less than long or complex work, and that family physicians should be paid
      for important tasks they currently are not, such as spending extra time with
      patients, phone and email clinical encounters, and extra paperwork. Subjects
      wanted shared savings when their decisions and actions created system
      efficiencies and savings. Some supported recent payment reforms such as monthly
      retainer fees and pay-for-performance bonuses. Others expressed skepticism about
      the negative consequences of each. Aligned incentives among all stakeholders was
      another common theme. CONCLUSIONS: Family physicians wanted less burdensome
      documentation requirements. They wanted to be paid more for complex work and work
      that does not include traditional face-to-face clinic visits, and they wanted the
      incentives of other stakeholders in the health care systems to be aligned with
      their priorities.

PMID- 24911307
TI  - Journeying through health disparities--two family physicians' stories.

PMID- 24911310
TI  - Transforming health care through education.

PMID- 24911313
TI  - Experiences of emotional abuse among women living with HIV and AIDS in Malawi.
AB  - Our aim for this study was to describe emotional abuse as it is experienced by
      women living with HIV and AIDS in Malawi. The study was conducted in the Lilongwe
      district in Malawi and used a descriptive phenomenological approach. Twelve women
      from two public health care clinics under the Lilongwe District Health Office
      were interviewed. Violating experiences that scarred the personhood and inherent
      value of being human were found to be the essence of their emotional abuse. Their
      husbands, family, and community members were responsible for the humiliation,
      abandonment, and blaming that caused them to feel hopeless. 

PMID- 24911311
TI  - Optic nerve head blood flow response to reduced ocular perfusion pressure by
      alteration of either the blood pressure or intraocular pressure.
AB  - PURPOSE: To test the hypothesis that blood flow autoregulation in the optic nerve
      head has less reserve to maintain normal blood flow in the face of blood pressure
      induced ocular perfusion pressure decrease than a similar magnitude intraocular
      pressure-induced ocular perfusion pressure decrease. MATERIALS AND METHODS:
      Twelve normal non-human primates were anesthetized by continuous intravenous
      infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle
      flowgraphy. In the first group of animals (n = 6), the experimental eye
      intraocular pressure was maintained at 10 mmHg using a saline reservoir connected
      to the anterior chamber. The blood pressure was gradually reduced by a slow
      injection of pentobarbital. In the second group (n = 6), the intraocular pressure
      was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both
      experimental groups, optic nerve head blood flow was measured continuously. The
      blood pressure and intraocular pressure were simultaneously recorded in all
      experiments. RESULTS: The optic nerve head blood flow showed significant
      difference between the two groups (p = 0.021, repeat measures analysis of
      variance). It declined significantly more in the blood pressure group compared to
      the intraocular pressure group when the ocular perfusion pressure was reduced to
      35 mmHg (p < 0.045) and below. There was also a significant interaction between
      blood flow changes and the ocular perfusion pressure treatment (p = 0.004,
      adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged
      blood flow difference between the two groups was due to the ocular perfusion
      pressure decrease. CONCLUSIONS: The results show that optic nerve head blood flow
      is more susceptible to an ocular perfusion pressure decrease induced by lowering
      the blood pressure compared with that induced by increasing the intraocular
      pressure. This blood flow autoregulation capacity vulnerability to low blood
      pressure may provide experimental evidence related to the hemodynamic
      pathophysiology in glaucoma.

PMID- 24911314
TI  - Effects of 5alpha-dihydrotestosterone and 17beta-estradiol on the mouse ovarian
      follicle development and oocyte maturation.
AB  - We have previously reported that androstenedione induces abnormalities of
      follicle development and oocyte maturation in the mouse ovary. In granulosa cells
      of the ovarian follicle, androstenedione is aromatized to 17beta-estradiol (E2).
      To determine whether the androgen or estrogen acts directly on the follicle to
      induce the above-mentioned abnormalities, we compared the effects of a non
      aromatizable androgen, 5alpha-dihydrotestosterone (DHT), with those of E2 on
      murine follicular development and oocyte maturation in a single follicle culture
      system. The high dose (10(-6) M) of DHT prompted normal follicular development,
      and there was no effect on oocyte meiotic maturation after stimulation with human
      chorionic gonadotropin (hCG) and epidermal growth factor (EGF). In contrast,
      culture with the high dose (10(-6) M) of E2 delayed follicular growth and also
      suppressed proliferation of granulosa cells and antrum formation. Furthermore,
      culture with E2 delayed or inhibited oocyte meiotic maturation, such as
      chromosome alignment on the metaphase plate and extrusion of the first polar
      body, after addition of hCG and EGF. In conclusion, these findings demonstrate
      that E2, but not DHT, induces abnormalities of follicular development, which
      leads to delay or inhibition of oocyte meiotic maturation.

PMID- 24911315
TI  - Large scale screening of digeneans for Neorickettsia endosymbionts using real
      time PCR reveals new Neorickettsia genotypes, host associations and geographic
      records.
AB  - Digeneans are endoparasitic flatworms with complex life cycles including one or
      two intermediate hosts (first of which is always a mollusk) and a vertebrate
      definitive host. Digeneans may harbor intracellular endosymbiotic bacteria
      belonging to the genus Neorickettsia (order Rickettsiales, family
      Anaplasmataceae). Some Neorickettsia are able to invade cells of the digenean's
      vertebrate host and are known to cause diseases of wildlife and humans. In this
      study we report the results of screening 771 digenean samples for Neorickettsia
      collected from various vertebrates in terrestrial, freshwater, brackish, and
      marine habitats in the United States, China and Australia. Neorickettsia were
      detected using a newly designed real-time PCR protocol targeting a 152 bp
      fragment of the heat shock protein coding gene, GroEL, and verified with nested
      PCR and sequencing of a 1371 bp long region of 16S rRNA. Eight isolates of
      Neorickettsia have been obtained. Sequence comparison and phylogenetic analysis
      demonstrated that 7 of these isolates, provisionally named Neorickettsia sp. 1-7
      (obtained from allocreadiid Crepidostomum affine, haploporids Saccocoelioides
      beauforti and Saccocoelioides lizae, faustulid Bacciger sprenti, deropegid
      Deropegus aspina, a lecithodendriid, and a pleurogenid) represent new genotypes
      and one (obtained from Metagonimoides oregonensis) was identical to a published
      sequence of Neorickettsia known as SF agent. All digenean species reported in
      this study represent new host records. Three of the 6 digenean families
      (Haploporidae, Pleurogenidae, and Faustulidae) are also reported for the first
      time as hosts of Neorickettsia. We have detected Neorickettsia in digeneans from
      China and Australia for the first time based on PCR and sequencing evidence. Our
      findings suggest that further surveys from broader geographic regions and wider
      selection of digenean taxa are likely to reveal new Neorickettsia lineages as
      well as new digenean host associations. 

PMID- 24911316
TI  - Predicting epileptic seizures in advance.
AB  - Epilepsy is the second most common neurological disorder, affecting 0.6-0.8% of
      the world's population. In this neurological disorder, abnormal activity of the
      brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs
      (AEDs) are used as long-term therapeutic solutions that control the condition. Of
      those treated with AEDs, 35% become resistant to medication. The unpredictable
      nature of seizures poses risks for the individual with epilepsy. It is clearly
      desirable to find more effective ways of preventing seizures for such patients.
      The automatic detection of oncoming seizures, before their actual onset, can
      facilitate timely intervention and hence minimize these risks. In addition,
      advance prediction of seizures can enrich our understanding of the epileptic
      brain. In this study, drawing on the body of work behind automatic seizure
      detection and prediction from digitised Invasive Electroencephalography (EEG)
      data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal
      Relabeling), is described. ASPPR facilitates the learning of predictive models
      targeted at recognizing patterns in EEG activity that are in a specific time
      window in advance of a seizure. It then exploits advanced machine learning
      coupled with the design and selection of appropriate features from EEG signals.
      Results, from evaluating ASPPR independently on 21 different patients, suggest
      that seizures for many patients can be predicted up to 20 minutes in advance of
      their onset. Compared to benchmark performance represented by a mean S1-Score
      (harmonic mean of Sensitivity and Specificity) of 90.6% for predicting seizure
      onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of:
      96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction
      between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19
      minutes in advance, and 94.2% for prediction between 20 and 25 minutes in
      advance. 

PMID- 24911317
TI  - Acute net stressor increases whole-body cortisol levels without altering whole
      brain monoamines in zebrafish.
AB  - Recent studies have started to examine the neurochemical and hormonal basis of
      behavior in zebrafish by examining biological correlates postmortem. However, it
      is unknown whether stress involved with experimental handling prior to
      euthanizing animals will have an impact on subsequent biological measures. In the
      current study, we expose zebrafish to a short net handling stressor (30 s) and
      examine the levels of monoamine neurotransmitters (dopamine, serotonin, and their
      metabolites) and whole-body cortisol at different intervals poststressor (0, 1,
      5, 10, and 15 min). We report a time-dependent increase in the levels of
      cortisol, but no alterations in the levels of dopamine, DOPAC (dopamine's
      metabolite), serotonin, or 5HIAA (serotonin's metabolite) poststressor. The
      results demonstrate cortisol levels are more responsive to this type of stimulus
      compared with neurochemical measures.

PMID- 24911318
TI  - Spinal cord stimulation (SCS) improves decreased physical activity induced by
      nerve injury.
AB  - Spinal cord stimulation (SCS) is used to manage treatment of neuropathic pain to
      reduce pain and hyperalgesia and to improve activity. Prior studies using animal
      models of neuropathic pain have shown that SCS reduces hyperalgesia; however, it
      is unclear whether SCS affects physical activity. Therefore, we tested whether
      nerve injury (spared nerve injury [SNI] model) reduced physical activity levels,
      and whether SCS could restore these decreased activity levels. We tested whether
      SCS given over a long duration (6 hr daily for 3 months) remained effective. We
      compared SNI with uninjured controls over 4 weeks, and SNI with sham SCS with SNI
      with active SCS (4 or 60 Hz at 90% motor threshold). We confirmed the presence of
      mechanical hyperalgesia by examining mechanical thresholds of the paw with von
      Frey filaments. Physical activity levels were monitored over 30 min in an
      automated activity chamber as follows: overall activity, distance traveled,
      grooming behaviors, and rearing. Measures were taken during SCS every 1-2 weeks
      for 3 months. Animals with SNI (and no or sham SCS) showed decreased withdrawal
      thresholds ipsilaterally and reduced physical activity (rearing, distance, lines
      crossed) for 3 months. Both 4- and 60-Hz SCS increased paw withdrawal threshold
      during and immediately after SCS through 3 months. Both 4- and 60-Hz SCS
      increased the overall activity (lines crossed), distance traveled, and rearing,
      but not grooming behaviors for 3 months. This effect remained similar across the
      3 months. Thus, measurement of spontaneous physical activity could be useful to
      examine nocifensive behaviors after nerve injury and is sensitive to SCS.

PMID- 24911319
TI  - Donepezil reverses nicotine withdrawal-induced deficits in contextual fear
      conditioning in C57BL/6J mice.
AB  - Withdrawal from chronic nicotine is associated with cognitive deficits. Therapies
      that ameliorate cognitive deficits during withdrawal aid in preventing relapse
      during quit attempts. Withdrawal-induced deficits in contextual learning are
      associated with nicotinic acetylcholine receptor upregulation. The aim of the
      present study was to determine if the acetylcholinesterase inhibitor donepezil
      has the ability to reverse nicotine withdrawal-induced deficits in contextual
      learning. Results demonstrated that low doses of donepezil, which do not enhance
      contextual learning or alter locomotor activity/anxiety-related behavior, can
      reverse nicotine withdrawal-induced deficits in contextual learning. Thus,
      donepezil may have therapeutic value for ameliorating cognitive deficits
      associated with nicotine withdrawal and for preventing relapse.

PMID- 24911321
TI  - Supramolecular polymeric materials via cyclodextrin-guest interactions.
AB  - CONSPECTUS: Cyclodextrins (CDs) have many attractive functions, including
      molecular recognition, hydrolysis, catalysis, and polymerization. One of the most
      important uses of CDs is for the molecular recognition of hydrophobic organic
      guest molecules in aqueous solutions. CDs are desirable host molecules because
      they are environmentally benign and offer diverse functions. This Account
      demonstrates some of the great advances in the development of supramolecular
      materials through host-guest interactions within the last 10 years. In 1990, we
      developed topological supramolecular complexes with CDs, polyrotaxane, and CD
      tubes, and these preparation methods take advantage of self-organization between
      the CDs and the polymers. The combination of polyrotaxane with alphaCD forms a
      hydrogel through the interaction of alphaCDs with the OH groups on poly(ethylene
      glycol). We categorized these polyrotaxane chemistries within main chain type
      complexes. At the same time, we studied the interactions of side chain type
      supramolecular complexes with CDs. In these systems the guest molecules modified
      the polymers and selectively formed inclusion complexes with CDs. The systems
      that used low molecular weight compounds did not show such selectivity with CDs.
      The multivalency available within the complex cooperatively enhances the
      selective binding of CD with guest molecules via the polymer side chains, a
      phenomenon that is analogous to binding patterns observed in antigen-antibody
      complexes. To incorporate the molecular recognition properties of CDs within the
      polymer side chains, we first prepared stimuli-responsive sol-gel switching
      materials through host-guest interactions. We chose azobenzene derivatives for
      their response to light and ferrocene derivatives for their response to redox
      conditions. The supramolecular materials were both redox-responsive and self
      healing, and these properties resulted from host-guest interactions. These sol
      gels with built in switches gave us insight for creating materials that were self
      healing or could serve as artificial muscle. Furthermore, we developed another
      self-healing material with CD inclusion complexes that showed selective self
      healing properties after its surface was cut. These CD self-healing materials do
      not include chemical cross-linkers; instead the inclusion complex of CDs with
      guest molecules stabilized the material's strength. However, by introducing
      chemical cross-linkers into the hydrogels, we produced materials that could
      expand and contract. The chemical cross-linked hydrogels with responsive groups
      bent in response to external stimuli, and the cross-linkers controlled the ratio
      of inclusion complexes. Furthermore, we used the molecular recognition of CDs to
      achieve macroscopic self-assemblies, and this chemistry can direct these
      macroscopic objects into even larger aggregated structures. As we have
      demonstrated, reversible host-guest interactions have tremendous potential for
      the creation of a wide variety of functional materials.

PMID- 24911320
TI  - Dopamine modulates novelty seeking behavior during decision making.
AB  - Novelty seeking refers to the tendency of humans and animals to explore novel and
      unfamiliar stimuli and environments. The idea that dopamine modulates novelty
      seeking is supported by evidence that novel stimuli excite dopamine neurons and
      activate brain regions receiving dopaminergic input. In addition, dopamine is
      shown to drive exploratory behavior in novel environments. It is not clear
      whether dopamine promotes novelty seeking when it is framed as the decision to
      explore novel options versus the exploitation of familiar options. To test this
      hypothesis, we administered systemic injections of saline or GBR-12909, a
      selective dopamine transporter (DAT) inhibitor, to monkeys and assessed their
      novelty seeking behavior during a probabilistic decision making task. The task
      involved pseudorandom introductions of novel choice options. This allowed monkeys
      the opportunity to explore novel options or to exploit familiar options that they
      had already sampled. We found that DAT blockade increased the monkeys' preference
      for novel options. A reinforcement learning (RL) model fit to the monkeys' choice
      data showed that increased novelty seeking after DAT blockade was driven by an
      increase in the initial value the monkeys assigned to novel options. However,
      blocking DAT did not modulate the rate at which the monkeys learned which cues
      were most predictive of reward or their tendency to exploit that knowledge. These
      data demonstrate that dopamine enhances novelty-driven value and imply that
      excessive novelty seeking-characteristic of impulsivity and behavioral addictions
      might be caused by increases in dopamine, stemming from less reuptake.

PMID- 24911322
TI  - The validity of microsensors to automatically detect bowling events and counts in
      cricket fast bowlers.
AB  - PURPOSE: Bowling workload is linked to injury risk in cricket fast bowlers. This
      study investigated the validity of microtechnology in the automated detection of
      bowling counts and events, including run-up distance and velocity, in cricket
      fast bowlers. METHOD: Twelve highly skilled fast bowlers (mean +/- SD age 23.5 +/
      3.7 y) performed a series of bowling, throwing, and fielding activities in an
      outdoor environment during training and competition while wearing a
      microtechnology unit (MinimaxX). Sensitivity and specificity of a bowling
      detection algorithm were determined by comparing the outputs from the device with
      manually recorded bowling counts. Run-up distance and run-up velocity were
      measured and compared with microtechnology outputs. RESULTS: No significant
      differences were observed between direct measures of bowling and nonbowling
      events and true positive and true negative events recorded by the MinimaxX unit
      (P = .34, r = .99). The bowling-detection algorithm was shown to be sensitive in
      both training (99.0%) and competition (99.5%). Specificity was 98.1% during
      training and 74.0% during competition. Run-up distance was accurately recorded by
      the unit, with a percentage bias of 0.8% (r = .90). The final 10-m (-8.9%, r =
      .88) and 5-m (-7.3%, r = .90) run-up velocities were less accurate. CONCLUSIONS:
      The bowling-detection algorithm from the MinimaxX device is sensitive to detect
      bowling counts in both cricket training and competition. Although specificity is
      high during training, the number of false positive events increased during
      competition. Additional bowling workload measures require further development.

PMID- 24911323
TI  - Prevalence patterns of avian Plasmodium and Haemoproteus parasites and the
      influence of host relative abundance in southern China.
AB  - Infectious diseases threaten the health and survival of wildlife populations.
      Consequently, relationships between host diversity, host abundance, and parasite
      infection are important aspects of disease ecology and conservation research.
      Here, we report on the prevalence patterns of avian Plasmodium and Haemoproteus
      infections and host relative abundance influence based on sampling 728 wild
      caught birds representing 124 species at seven geographically widespread sites in
      southern China. The overall prevalence of two haemoprotozoan parasites,
      Plasmodium and Haemoproteus, was 29.5%, with 22.0% attributable to Haemoproteus
      and 7.8% to Plasmodium. Haemoproteus prevalence differed significantly among
      different avian host families, with the highest prevalence in Nectariniidae,
      Pycnonotidae and Muscicapidae, whereas Plasmodium prevalence varied significantly
      among host species. Seventy-nine mitochondrial lineages including 25 from
      Plasmodium and 54 from Haemoproteus were identified, 80% of which were described
      here for the first time. The phylogenetic relationships among these parasites
      indicated stronger host-species specificity for Haemoproteus than Plasmodium.
      Well-supported host-family (Timaliidae) specific clades were found in both
      Plasmodium and Haemoproteus. The Haemoproteus tree shows regional subclades,
      whereas the Plasmodium clades are "scattered" among different geographical
      regions. Interestingly, there were statistically significant variations in the
      prevalence of Plasmodium and Haemoproteus among the geographical regions.
      Furthermore, the prevalence of Plasmodium and Haemoproteus were not significantly
      correlated with host relative abundance. Further efforts will focus on exploring
      the relationships between parasite prevalence and sex, age, and immune defense of
      the host. 

PMID- 24911324
TI  - A method for modeling growth of organs and transplants based on the general
      growth law: application to the liver in dogs and humans.
AB  - Understanding biological phenomena requires a systemic approach that incorporates
      different mechanisms acting on different spatial and temporal scales, since in
      organisms the workings of all components, such as organelles, cells, and organs
      interrelate. This inherent interdependency between diverse biological mechanisms,
      both on the same and on different scales, provides the functioning of an organism
      capable of maintaining homeostasis and physiological stability through numerous
      feedback loops. Thus, developing models of organisms and their constituents
      should be done within the overall systemic context of the studied phenomena. We
      introduce such a method for modeling growth and regeneration of livers at the
      organ scale, considering it a part of the overall multi-scale biochemical and
      biophysical processes of an organism. Our method is based on the earlier
      discovered general growth law, postulating that any biological growth process
      comprises a uniquely defined distribution of nutritional resources between
      maintenance needs and biomass production. Based on this law, we introduce a liver
      growth model that allows to accurately predicting the growth of liver transplants
      in dogs and liver grafts in humans. Using this model, we find quantitative growth
      characteristics, such as the time point when the transition period after surgery
      is over and the liver resumes normal growth, rates at which hepatocytes are
      involved in proliferation, etc. We then use the model to determine and quantify
      otherwise unobservable metabolic properties of livers. 

PMID- 24911325
TI  - Flow-induced signal misallocation artifacts in two-point fat-water chemical shift
      MRI.
AB  - PURPOSE: Two-point fat-water separation methods are increasingly being used for
      chest and abdominal MRI and have recently been introduced for use in MR
      angiography of the lower extremities. With these methods, flowing spins can
      accumulate unintended phase shifts between the echo times. The purpose of this
      study is to demonstrate that these phase shifts can lead to inaccurate signals in
      the water and fat images. THEORY AND METHODS: In vitro experiments were conducted
      at 1.5T and 3.0T using a stenosis-mimicking phantom and a computer-controlled
      pump to image a range of physiologically relevant velocities. RESULTS: In the
      phantom images acquired using bipolar readout gradients, fat-water signal
      inaccuracies were visible in regions of flow, with increasing severity as the
      flow rate was increased. Additionally, similar effects were observed in regions
      of high flow in clinical chest and liver exams. In the phantom images, the effect
      was eliminated by using a dual-pass method without bipolar readout gradients.
      CONCLUSION: When using fat-water separation methods with bipolar readout
      gradients, phase shifts caused by the motion of spins can lead to signal
      inaccuracies in the fat and water images. These artifacts can be mitigated by
      using approaches that do not use bipolar readout gradients.

PMID- 24911326
TI  - Acupuncture in IVF: A review of current literature.
AB  - Women's choice to delay fertility due to various reasons is making subfertility a
      growing problem and increased use of IVF as a last resort. Despite advances in
      the technology, IVF success remains low, especially in older women. Hence, many
      of these women need to undergo several cycles of IVF and are faced with
      unprecedented anxiety and frustration. In desperation, they resort to anything
      that might increase the success of their IVF treatment. Acupuncture has gained
      popularity among the various complementary medicines available and many go
      privately to have acupuncture while undergoing IVF. Since 1999, in spite of
      multiple trials and systematic reviews, the beneficial effect of acupuncture in
      improving the success of IVF remains unproven and debatable. As clinicians, we
      face the dilemma of what to suggest to our patients when asked about having
      acupuncture during IVF, given that different meta-analyses have come to different
      conclusions. Hence, this review is conducted with the aim to summarise the
      available literature and provide a better insight into this complex and
      controversial topic.

PMID- 24911328
TI  - Platinum corroles.
AB  - Platinum has been inserted into corroles for the first time and three oxidized
      Pt(IV)(corrole(2-))ArAr' complexes have been structurally characterized. The
      Soret maxima of these complexes exhibit an unusually strong dependence on the
      meso-aryl substituents on the corrole, indicating aryl -> corrole(2-) charge
      transfer character in these transitions. 

PMID- 24911327
TI  - The Immunology Quality Assessment Proficiency Testing Program for CD3+4+ and
      CD3+8+ lymphocyte subsets: a ten year review via longitudinal mixed effects
      modeling.
AB  - Since 1999, the National Institute of Allergy and Infectious Diseases Division of
      AIDS (NIAID DAIDS) has funded the Immunology Quality Assessment (IQA) Program
      with the goal of assessing proficiency in basic lymphocyte subset
      immunophenotyping for each North American laboratory supporting the NIAID DAIDS
      HIV clinical trial networks. Further, the purpose of this program is to
      facilitate an increase in the consistency of interlaboratory T-cell subset
      measurement (CD3(+)4(+)/CD3(+)8(+) percentages and absolute counts) and likewise,
      a decrease in intralaboratory variability. IQA T-cell subset measurement
      proficiency testing was performed over a ten-year period (January 2003-July
      2012), and the results were analyzed via longitudinal analysis using mixed
      effects models. The goal of this analysis was to describe how a typical
      laboratory (a statistical modeling construct) participating in the IQA Program
      performed over time. Specifically, these models were utilized to examine trends
      in interlaboratory agreement, as well as successful passing of proficiency
      testing. Intralaboratory variability (i.e., precision) was determined by the
      repeated measures variance, while fixed and random effects were taken into
      account for changes in interlaboratory agreement (i.e., accuracy) over time. A
      flow cytometer (single-platform technology, SPT) or a flow cytometer/hematology
      analyzer (dual-platform technology, DPT) was also examined as a factor for
      accuracy and precision. The principal finding of this analysis was a significant
      (p<0.001) increase in accuracy of T-cell subset measurements over time,
      regardless of technology type (SPT or DPT). Greater precision was found in SPT
      measurements of all T-cell subset measurements (p<0.001), as well as greater
      accuracy of SPT on CD3(+)4(+)% and CD3(+)8(+)% assessments (p<0.05 and p<0.001,
      respectively). However, the interlaboratory random effects variance in DPT
      results indicates that for some cases DPT can have increased accuracy compared to
      SPT. Overall, these findings demonstrate that proficiency in and among IQA
      laboratories have, in general, improved over time and that platform type
      differences in performance do exist. 

PMID- 24911329
TI  - Cervical insufficiency and placenta accreta after prior pelvic radiation.

PMID- 24911331
TI  - The effect of hormone therapy on biochemical and ultrasound parameters associated
      with atherosclerosis in 46,XY DSD individuals with female phenotype.
AB  - The aim of this study was to evaluate the effect of hormone therapy (HT) in the
      endothelial function of 46,XY disorders of sexual development (DSD) patients with
      female phenotype. Biochemical and ultrasound measurements were performed in 20
      patients at initiation of oral 2 mg 17beta-estradiol/1 mg norethisterone acetate,
      and after 6 months of therapy. Lipid profile, including total cholesterol (TC),
      LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as
      levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined.
      Ultrasonographic examinations included evaluation of flow-mediated dilatation
      (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT
      raised HDL (35.4 mg/dl versus 40.1 mg/dl, p = 0.019) while lowering TG (166 mg/dl
      versus 109 mg/dl, p = 0.026) and AIP (0.24 versus 0.04, p = 0.007). No changes
      were noted in TC and LDL (215.7 mg/dl versus 192.25 mg/dl and 87.46 mg/dl versus
      76.35 mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05
      ng/ml versus 2.20 ng/ml, p = 0.002) and E-selectin (73.98 ng/ml versus 56.73
      ng/ml, p = 0.004). No change was observed in Thrombomodulin and vWf (11.76 ng/ml
      versus 13.90 ng/ml and 80.75% versus 79.55%, respectively). FMD improved
      significantly (5.4% versus 8.15%, p = 0.003), while only carotid bulb IMT
      decreased significantly (0.65 mm versus 0.60 mm, p = 0.018). Overall, HT was
      found to improve biochemical and ultrasound markers of endothelial function in
      46,XY DSD patients with female phenotype.

PMID- 24911332
TI  - A European survey on attitudes towards pain and end-of-life issues in locked-in
      syndrome.
AB  - OBJECTIVES: Patients with locked-in syndrome often self-report a higher quality
      of life than generally expected. This study reports third-person attitudes
      towards several salient issues on locked-in syndrome. METHODS: Close-ended survey
      among conference attendees from 33 European countries. Analysis included chi
      square tests and logistic regressions. RESULTS: From the 3332 respondents (33%
      physicians, 18% other clinicians, 49% other professions; 47% religious), 90%
      agreed that patients with locked-in syndrome can feel pain. The majority (75%)
      disagreed with treatment withdrawal, but 56% did not wish to be kept alive if
      they imagined themselves in this condition (p < 0.001). Religious and southern
      Europeans opposed to treatment withdrawal more often than non-religious (p <
      0.001) and participants from the North (p = 0.001). When the locked-in syndrome
      was compared to disorders of consciousness, more respondents endorsed that being
      in a chronic locked-in syndrome was worse than being in a vegetative state or
      minimally conscious state for patients (59%) than they thought for families (40%,
      p < 0.001). CONCLUSIONS: Personal characteristics mediate opinions about locked
      in syndrome. The dissociation between personal preferences and general opinions
      underlie the difference in perspective in disability. Ethical responses to
      dilemmas involving patients with locked-in syndrome should consider the diverging
      ethical attitudes of stakeholders.

PMID- 24911330
TI  - Acute high-level exposure to WTC particles alters expression of genes associated
      with oxidative stress and immune function in the lung.
AB  - First responders (FR) present at Ground Zero in the first 72 h after the World
      Trade Center (WTC) collapsed have progressively exhibited significant respiratory
      injuries. The few toxicology studies performed to date evaluated effects from
      just fine (< 2.5 um) WTC dusts; none examined health effects/toxicities from
      atmospheres bearing larger particle sizes, despite the fact the majority (> 96%)
      of dusts were > 10 um and most FR likely entrained dusts by mouth breathing.
      Using a system that generated/delivered supercoarse (10-53 um) WTC dusts to F344
      rats (in a manner that mimicked FR exposures), this study sought to examine
      potential toxicities in the lungs. In this exploratory study, rats were exposed
      for 2 h to 100 mg WTC dust/m(3) (while under isoflurane [ISO] anesthesia) or an
      air/ISO mixture; this dose conservatively modeled likely exposures by mouth
      breathing FR facing ~750-1000 mg WTC dust/m(3). Lungs were harvested 2 h post
      exposure and total RNA extracted for subsequent global gene expression analysis.
      Among the >  1000 genes affected by WTC dust (under ISO) or ISO alone, 166 were
      unique to the dust exposure. In many instances, genes maximally-induced by the
      WTC dust exposure (relative to in naive rats) were unchanged/inhibited by ISO
      only; similarly, several genes maximally inhibited in WTC dust rats were largely
      induced/unchanged in rats that received ISO only. These outcomes reflect likely
      contrasting effects of ISO and the WTC dust on lung gene expression. Overall, the
      data show that lungs of rats exposed to WTC dust (under ISO) - after accounting
      for any impact from ISO alone - displayed increased expression of genes related
      to lung inflammation, oxidative stress, and cell cycle control, while several
      involved in anti-oxidant function were inhibited. These changes suggested acute
      inflammogenic effects and oxidative stress in the lungs of WTC dust-exposed rats.
      This study, thus, concludes that a single very high exposure to WTC dusts could
      potentially have adversely affected the respiratory system - in terms of early
      inflammatory and oxidative stress processes. As these changes were not compared
      with other types of dusts, the uniqueness of these WTC-mediated effects remains
      to be confirmed. It also still remains to be determined if these effects might
      have any relevance to chronic lung pathologies that became evident among FR who
      encountered the highest dust levels on September 11, 2001 and the 2 days
      thereafter. Ongoing studies using longer-range post-exposure analyses (up to 1
      year or more) will help to determine if effects seen here on genes were acute,
      reversible, or persistent, and associated with corresponding
      histopathologic/biochemical changes in situ.

PMID- 24911333
TI  - Disparities in modern contraception use among women in the Democratic Republic of
      Congo: a cross-sectional spatial analysis of provincial variations based on
      household survey data.
AB  - This study investigates inequalities at the province level of the use of modern
      contraception and the proportion of short birth intervals among women in the DRC
      using data from the 2007 Demographic and Health Survey. Logistic regression and
      Bayesian geo-additive models were used. The posterior odds ratio and the
      associated 95% credible interval (95% CI) were estimated using Markov Chain Monte
      Carlo (MCMC) techniques. Posterior spatial effects were mapped at the province
      level with the associated posterior probability maps showing statistical
      significance at 5%. The overall rates of modern contraception use among the
      entire sample of women (15-49 years old; N = 7172) and youth (15-24 years old; N
      = 1389) were 5.7% and 6.0% respectively. However, there was striking variation in
      contraceptive use between the two groups across provinces with a clear east-to
      west gradient. The highest use in the total sample was in Nord-Kivu (OR 1.32; 95%
      CI 1.12, 1.55) and Bas Congo provinces (1.47; 1.22, 1.78). For the youth, the
      highest use was observed in Nord-Kivu (1.19; 0.92, 1.65). In multivariate
      Bayesian geo-additive regression analyses among the entire sample of women,
      factors consistently associated with lower use of modern contraception were
      living in rural areas (0.71; 0.62, 0.82), living in low-income households (0.67;
      0.54, 0.80) and having no education (0.83; 0.67, 0.97). For the youth sample,
      living in low-income households (0.57; 0.41, 0.84) and no breast-feeding (0.64;
      0.47, 0.86) were consistently associated with a lower use of modern
      contraception. The study shows a distinct geographic pattern in the use of modern
      contraception in youth and the entire sample of women in the DRC, suggesting a
      potential role for socioeconomic factors, such as accessibility, affordability
      and availability, as well as environmental factors at the province level beyond
      individual-level risk factors.

PMID- 24911334
TI  - Translation of incremental talk test responses to steady-state exercise training
      intensity.
AB  - PURPOSE: The Talk Test (TT) is a submaximal, incremental exercise test that has
      been shown to be useful in prescribing exercise training intensity. It is based
      on a subject's ability to speak comfortably during exercise. This study defined
      the amount of reduction in absolute workload intensity from an incremental
      exercise test using the TT to give appropriate absolute training intensity for
      cardiac rehabilitation patients. METHODS: Patients in an outpatient
      rehabilitation program (N = 30) performed an incremental exercise test with the
      TT given every 2-minute stage. Patients rated their speech comfort after reciting
      a standardized paragraph. Anything other than a "yes" response was considered the
      "equivocal" stage, while all preceding stages were "positive" stages. The last
      stage with the unequivocally positive ability to speak was the Last Positive
      (LP), and the preceding stages were (LP-1 and LP-2). Subsequently, three 20
      minute steady-state training bouts were performed in random order at the absolute
      workload at the LP, LP-1, and LP-2 stages of the incremental test. Speech
      comfort, heart rate (HR), and rating of perceived exertion (RPE) were recorded
      every 5 minutes. RESULTS: The 20-minute exercise training bout was completed
      fully by LP (n = 19), LP-1 (n = 28), and LP-2 (n = 30). Heart rate, RPE, and
      speech comfort were similar through the LP-1 and LP-2 tests, but the LP stage was
      markedly more difficult. CONCLUSION: Steady-state exercise training intensity was
      easily and appropriately prescribed at intensity associated with the LP-1 and LP
      2 stages of the TT. The LP stage may be too difficult for patients in a cardiac
      rehabilitation program.

PMID- 24911335
TI  - Anti-inflammatory and antioxidant activities of Costus afer Ker Gawl. hexane leaf
      fraction in arthritic rat models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Costus afer Ker Gawl is an indigenous tropical
      African medicinal plant used as therapy in the treatment of inflammatory ailments
      such as rheumatoid arthritis. This study was designed to evaluate the anti
      inflammatory and antioxidant activities of the hexane fraction of C. afer leaves
      (CAHLF). MATERIALS AND METHODS: The anti-inflammatory effect of varying doses of
      CAHLF on carrageenan, arachidonic acid, and formaldehyde induced arthritis in
      male albino rats' models were investigated in order to study the acute
      inflammatory phase. Complete Freund's Adjuvant (CFA)-induced arthritis model was
      used to study the chronic inflammatory phase. Two known anti-inflammatory drugs,
      Diclofenac sodium (non-steroidal anti-inflammatory drug [NSAID]) and prednisolone
      (glucocorticoid [steroidal drug]) were used as standards for comparison. Various
      biochemical indices viz. superoxide dismutase (SOD), catalase (CAT), glutathione
      S-transferase (GST), reduced glutathione (GSH) and malondialdehyde (MDA),
      aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline
      phosphatase (ALP), total bilirubin (TB), total protein (TP), globulin and albumin
      levels were assayed using spectrophotometric methods. RESULTS: Control animals in
      which arthritis have been induced using carrageenan, arachidonic acid,
      formaldehyde or CFA showed significant increases (P<0.05) in paw edema when
      compared with normal animals. Treatment of the arthritis induced rats with CAHLF
      significantly (P<0.05) suppressed the edema. in vivo antioxidant study showed
      that CAHLF treated animals had a significantly (P<0.05) elevated GSH level, SOD,
      CAT and GST activities while MDA levels were significantly (P<0.05) reduced in
      the plasma, liver, kidney and brain. CAHLF treated rats had a significantly
      (P<0.05) reduced plasma AST, ALT and ALP. Plasma TP, globulin, TB levels were
      reduced while albumin levels were elevated in CAHLF treated animals. CONCLUSIONS:
      CAHLF possesses substantial anti-inflammatory and antioxidant activities against
      inflammatory diseases especially arthritis. It could be considered as a choice
      candidate in pharmaceutical anti-inflammatory drug development.

PMID- 24911336
TI  - Cytotoxic activity evaluation of some medicinal plants, selected from Iranian
      traditional medicine Pharmacopoeia to treat cancer and related disorders.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: By studying the Iranian Traditional Medicine
      (ITM) Pharmacopoeia, we have collected information about medicinal plants which
      had been used to manage cancer-like disorders over eight hundred years, from
      medieval to the early modern era. Exploring the ITM herbal knowledge, the
      selected species have been subjected to MTT assay for examining their in vitro
      cyototoxic activity. MATERIALS AND METHODS: Cancer was reviewed through the ITM
      and some terminologies were acquired. Five ITM Pharmacopoeia in Arabic and
      Persian languages from 10th to 18th century AD were explored. These Pharmacopoeia
      contained the ITM plants which were used to cure cancer and cancer-like diseases.
      The ITM names were matched with the scientific names. Then the medicinal plants
      were collected, authenticated and were evaluated for cytotoxic activity using MTT
      assay, against MCF-7, HepG-2, A-549 and HT-29 cell lines. Finally, the apoptosis
      induction ability of the most cytotoxic medicinal plant was investigated by
      activated caspase 3 inspection in MCF-7 cell line. RESULTS: Six species of the
      evaluated medicinal plants revealed cytotoxic activity. The most cytotoxicity was
      observed in Tanacetum polycephalum subsp. argyrophyllum (K.Koch) Podlech with
      IC50 values of 28.3 MUg mL(-1), 53.9 MUg mL(-1) and 43.3 MUg mL(-1) against MCF
      7, A-549 and HT-29 cell lines, respectively. Caspase 3 activation was also
      observed in MCF-7 cells by Tanacetum polycephalum subsp. argyrophyllum. This is
      the first time that the cytotoxic activity of this species has been reported.
      CONCLUSION: In the present study, some reliable references of ITM have been
      introduced and though many technical difficulties, linguistic problems and some
      other hindrances were encountered during the study, using traditional medicine
      texts for medicinal plant selection could be considered as a helpful starting
      point in the field of cancer drug discovery.

PMID- 24911337
TI  - Ethnoecology of Oxalis adenophylla Gillies ex Hook. & Arn.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: We studied the ethnoecological knowledge of
      medicinal Oxalis adenophylla in 3 rural villages of north Patagonia, Argentina.
      To evaluate links between use frequency, ethnoecological knowledge, sociocultural
      variables and the conservation status of this plant. MATERIALS AND METHOD: Forty
      informants were interviewed in relation to their knowledge, use, perception and
      the ecology of Oxalis adenophylla. Sociocultural variables were also documented,
      such as age, gender, size of family group living in the house, economic
      activities and ethnic self-determination. The abundance and availability of these
      plants were estimated in two villages, by measuring the number of plants per
      area, their weight and the relation between time invested and biomass collected.
      We tested frequency of use and age with Spearman's rank correlation coefficient.
      The relation between use frequency and gender, family group, economic activities,
      and ethnic self-determination of the informants was tested with the Mann Whitney
      non parametric test. An index of ethnoecological knowledge was constructed and
      correlated with use frequency through Spearman's rank correlation. To estimate
      conservation status we established a local risk index, taking both intrinsic and
      extrinsic parameters for this species into account. RESULTS: Regionally, Oxalis
      adenophylla is a plant known for its medicinal, alimentary and ornamental
      properties, but it has been poorly studied from a pharmacological point of view.
      Locally, the leaves of the plant are harvested for the preparation of
      "tortillas", which are stored and consumed in the cold months of the year for the
      treatment of flu fevers (95% of informants). Informants know the value of its
      root as a nutrient source and 35.8% reported its consumption. Use is sporadic and
      involves the harvesting of a mean of one root per year, which is eaten raw in
      situ. Only 12% of informants mentioned the plant's ornamental feature. The
      ethnoecological knowledge of Oxalis adenophylla included references to specific
      environments where the plant grows, its phenology and morphological and
      organoleptic characteristics, appropriate times for harvesting, and animals that
      forage for this species. The informants with the greatest ethnoecological
      knowledge harvested leaves and roots most frequently. The frequency of use did
      not differ in relation to age or gender. In contrast, frequency of use was the
      highest when the informant lived with several generations at home, maintained
      traditional animal husbandry practices and when they considered themselves as
      belonging to the Mapuche people. Informants perceived low abundance and
      availability of the plant in the environment, restricted by the great distances
      involved in obtaining them, seasonality, and in particular, difficulty in finding
      the roots. Informants believe that the plant is sensitive and it should be
      harvested in such a way as to ensure no damage to the whole plant, allowing
      resprouting. Our ecological measurements agreed with this perception. The local
      risk index for the plant was medium. CONCLUSION: In Patagonian Argentina, Oxalis
      adenophylla is a multipurpose species widely used for its medicinal properties
      but less for its edible roots and ornamental features. In the rural communities
      where we worked, frequency of use seems to depend on individual ethnoecological
      knowledge, the practice of indigenous worldview, living in households interacting
      with other generations and maintaining the activity of cattle raising. Locally,
      the main risk for the plant is the particular environment where it grows,
      characterized by slopes vulnerable to erosion. The human practice of local use
      could promote the conservation of this species through the understanding of its
      sensitivity to harvesting, and its insipient cultivation. This research shows the
      importance of obtaining a general overview of useful wild species used by local
      people.

PMID- 24911340
TI  - Modulation of stimulus contrast on the human pupil orienting response.
AB  - The sudden appearance of a novel stimulus initiates a series of responses to
      orient the body for appropriate actions, including not only shifts of gaze and
      attention, but also transient pupil dilation. Modulation of pupil dynamics by
      stimulus properties is less understood, although its effects on other components
      of orienting have been extensively explored. Microstimulation of the superior
      colliculus evoked transient pupil dilation, and the initial component of pupil
      dilation evoked by microstimulation was similar to that elicited by the
      presentation of salient sensory stimuli, suggesting a coordinated role of the
      superior colliculus on this behavior, although evidence in humans is yet to be
      established. To examine pupil orienting responses in humans, we presented visual
      stimuli while participants fixated on a central visual spot. Transient pupil
      dilation in humans was elicited after presentation of a visual stimulus in the
      periphery. The evoked pupil responses were modulated systematically by stimulus
      contrast, with faster and larger pupil responses triggered by higher contrast
      stimuli. The pupil response onset latencies for high contrast stimuli were
      similar to those produced by the light reflex and significantly faster than the
      darkness reflex, suggesting that the initial component of pupil dilation is
      probably mediated by inhibition of the parasympathetic pathway. The contrast
      modulation was pronounced under different levels of baseline pupil size.
      Together, our results demonstrate visual contrast modulation on the orienting
      pupil response in humans. 

PMID- 24911339
TI  - Ethnobotanical study on medicinal plants in Gecitli and its surrounding (Hakkari
      Turkey).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper provides significant ethnobotanical
      information on medicinal plants in the Gecitli Township in the Eastern Anatolia
      Region. Recording such data calls for urgency this is the first ethnobotanical
      study in which statistical calculations about plants are carried out by means of
      the FIC method in Eastern (Hakkari) part of Turkey. Aim of the study This study
      aims to identify the wild plants collected for medicinal purposes by locals of
      Gecitli which is located in the Eastern Anatolia Region of Turkey, and to
      identify the uses and local names of these wild plants. MATERIALS AND METHODS: A
      field study had been carried out for a period of approximately 2 years (2008
      2010). During this period, 70 plants taxa and one mushroom were collected.
      Demographic characteristics of participants, names of the local plants, their
      utilized parts and preparation methods were investigated and recorded. The plant
      taxa were collected within the scope of the study; and herbarium materials were
      prepared. In addition, the relative significance value of the taxa was
      determined, and informant consensus factor (FIC) was calculated for the medicinal
      plants included in the study. RESULTS: We have found out in the literature review
      of the plants included in our study that 70 plant taxa and one mushroom are
      already used for medicinal purposes while 11 plants are not available among the
      records in the literature. The most common families are Asteraceae, Apiaceae,
      Lamiaceae, Rosaceae, Euphorbiaceae, Fabaceae, and Malvaceae. We include in our
      study and report for the first time the medicinal uses of Alchemilla hessii
      Rothm., Cirsium pubigerum (Desf.) DC. var. spinosum Pet., Diplotaenia
      cachrydifolia Boiss., Euphorbia macrocarpa Boiss. & Buhse, Galium consanguineum
      Boiss., Inula helenium L. subsp. vanensis Grierson, Johrenia dichotoma DC. subsp.
      sintenisii Bornm., Pelargonium quercetorum Agnew, Rosa heckeliana Tratt. subsp.
      vanheurckiana (Crep.) O. Nilsson, Salix aegyptiaca L., Taraxacum montanum (C.A.
      Mey.) DC. Names of local plants in Turkey vary especially due to vernaculars. The
      plants that the locals of Gecitli use are called with the same or different local
      names in various parts of Anatolia. CONCLUSION: We found out that locals living
      in the research area use for therapeutic purpose 70 plants taxa and one mushroom
      which belong to 28 families. Turkish citizens with different ethnic backgrounds
      took the questionnaire. These people use these wild plants in treatment of
      several diseases. Comparison of the data obtained in this study with the
      experimental data obtained in the previous laboratory studies on the wild plants
      which grow in Gecitli proved ethnobotanical usages to a great extent. Literature
      review indicated that the therapeutic plants that grow in Gecitli are used in
      different parts of the world for the treatment of similar diseases.

PMID- 24911338
TI  - Some Nigerian anti-tuberculosis ethnomedicines: a preliminary efficacy
      assessment.
AB  - ETHNOPHARMACOLOGICAL SIGNIFICANCE: Nigerian herbalists possess indigenous
      ethnomedicinal recipes for the management of tuberculosis and related ailments. A
      collaborative preliminary modern scientific evaluation of the efficacy of some
      Nigerian ethnomedicines used by traditional medicine practitioners (TMPs) in the
      management of tuberculosis and related ailments has been carried out. MATERIALS
      AND METHODS: Ethnomedicinal recipes (ETMs) were collected from TMPs from
      locations in various ecological zones of Nigeria under a collaborative
      understanding. The aqueous methanolic extracts of the ETMs were screened against
      Mycobacterium bovis, BCG and Mycobacterium tuberculosis strain H37Rv using the
      broth microdilution method. RESULTS: Extracts of ETMs screened against BCG showed
      69% activity against the organism. The activities varied from weak, <=2500 ug/mL
      to highly active, 33 ug/mL 64% of the extracts were active against Mycobacterium
      tuberculosis The activities of the extracts against Mycobacterium tuberculosis
      varied from weak, <=2500 ug/mL to highly active, 128 ug/mL. There was 77%
      agreement in results obtained using BCG or Mycobacterium tuberculosis as test
      organisms. CONCLUSION: The results show clear evidence for the efficacy of the
      majority of indigenous Nigerian herbal recipes in the ethnomedicinal management
      of tuberculosis and related ailments. BCG may be effectively used, to a great
      extent, as the organism for screening for potential anti-Mycobacterium
      tuberculosis agents. A set of prioritization criteria for the selection of plants
      for initial further studies for the purpose of antituberculosis drug discovery
      research is proposed.

PMID- 24911341
TI  - Evolution of the global burden of viral infections from unsafe medical
      injections, 2000-2010.
AB  - BACKGROUND: In 2000, the World Health Organization estimated that, in developing
      and transitional countries, unsafe injections accounted for respectively 5%, 32%
      and 40% of new infections with HIV, hepatitis B virus (HBV) and hepatitis C virus
      (HCV). Safe injection campaigns were organized worldwide. The present study
      sought to measure the progress in reducing the transmission of these viruses
      through unsafe injections over the subsequent decade. METHODS: A mass action
      model was updated, to recalculate the number of injection-related HIV, HCV and
      HBV infections acquired in 2000 and provide estimates for 2010. Data about the
      annual number of unsafe injections were updated. HIV prevalence in various
      regions in 2000 and 2010 were calculated from UNAIDS data. The ratio of HIV
      prevalence in healthcare settings compared to the general population was
      estimated from a literature review. Improved regional estimates of the prevalence
      of HCV seropositivity, HBsAg and HBeAg antigenemia were used for 2000 and 2010.
      For HIV and HCV, revised estimates of the probability of transmission per episode
      of unsafe injection were used, with low and high values allowing sensitivity
      analyses. RESULTS: Despite a 13% population growth, there was a reduction of
      respectively 87% and 83% in the absolute numbers of HIV and HCV infections
      transmitted through injections. For HBV, the reduction was more marked (91%) due
      to the additional impact of vaccination. While injections-related cases had
      accounted for 4.6%-9.1% of newly acquired HIV infections in 2000, this proportion
      decreased to 0.7%-1.3% in 2010, when unsafe injections caused between 16,939 and
      33,877 HIV infections, between 157,592 and 315,120 HCV infections, and 1,679,745
      HBV infections. CONCLUSION: From 2000 to 2010, substantial progress was made in
      reducing the burden of HIV, HCV and HBV infections transmitted through
      injections. In some regions, their elimination might become a reasonable public
      health goal.

PMID- 24911342
TI  - Intra-arterial methylene blue injection into ex vivo colorectal cancer specimens
      improves lymph node staging accuracy: a randomized controlled trial.
AB  - AIM: A randomized controlled trial was carried out to study the effect of a
      recently proposed technique of ex vivo intra-arterial methylene blue injection of
      the surgical specimen removed for colorectal cancer on lymph node harvest and
      staging. METHOD: Between May 2012 and February 2013, 100 consecutive colorectal
      cancer resection specimens in a single institution were randomly assigned to
      intervention (methylene blue injection) and control (standard manual palpation
      technique) groups before formalin fixation. The specimen was then examined by the
      histopathologist for lymph nodes. RESULTS: Both groups were similar for age, sex,
      site of tumour, operation and tumour stage. In the intervention group, a higher
      number of nodes was found [median 23 (5-92) vs. 15 (5-37), P < 0.001], with only
      one specimen not achieving the recommended minimum standard of 12 nodes [1/50
      (2%) vs. 8/50 (16%), P = 0.014]. However, there was no upstaging effect in the
      intervention group [23/50 (46.0%) vs. 20/50 (40.0%); P = 0.686]. With a
      significantly lower number of nodes harvested in rectal cancer, the positive
      effect of the intervention was particularly observed in the patients who
      underwent preoperative neoadjuvant radiotherapy [median 30 nodes (12-57) vs. 11
      (7-15); P = 0.011; proportion of cases with < 12 nodes 0/5 vs. 5/8 (62.5%), P =
      0.024]. CONCLUSION: Ex vivo intra-arterial methylene blue injection increases
      lymph node yield and can help to reduce the number of cases with a lower-than
      recommended number of nodes, particularly in patients with rectal cancer having
      neoadjuvant treatment. The technique is easy to perform, cheap and saves time.

PMID- 24911343
TI  - Evidence-based evaluation for allergies to avoid inappropriate testing,
      diagnosis, and treatment.

PMID- 24911344
TI  - Phase diagram of solid-phase transformation in amorphous carbon nanorods.
AB  - The transformations of amorphous carbon nanorods with different diameters and
      densities upon heating up to different temperatures are studied with density
      functional-based tight-binding molecular dynamics. Phase diagrams with assorted
      transformed sp(2) nanostructures depending on both temperatures and line density,
      under different heating treatments, are presented to place the observations in
      perspective. Under instant heating, the lowest line density at which a carbon
      nanotube can form is 8 A(-1), while a double-walled carbon nanotube can form at a
      linear density of 19-20 A(-1) and higher. Under gradual heating, both partially
      unzipped carbon nanotubes and carbon nanoscrolls are formed as notable
      intermediate structural motifs. This work sheds light on the microscopic
      mechanism of various sp(2) nanostructural formations with the featured motifs
      highlighted as important intermediates, which will serve as an important guide in
      producing graphene nanoribbons, single-walled and double-walled carbon nanotubes,
      and carbon nanoscrolls from amorphous carbon nanorods. 

PMID- 24911345
TI  - Controllable electrofusion of lipid vesicles: initiation and analysis of
      reactions within biomimetic containers.
AB  - We present a microfluidic device that is able to trap multiple giant unilamellar
      vesicles (GUVs) and initiate electrofusion via integrated microelectrodes. PDMS
      posts were designed to trap and isolate two or more vesicles. Electrodes
      patterned onto the glass surface of the microchannels are able to apply a short,
      high voltage pulse across the traps for controllable electrofusion of the GUVs.
      The entire array of traps and electrodes are designed such that an average of 60
      individual fusion experiments can be performed on-chip. An assay based on Forster
      resonance energy transfer (FRET) is performed to show successful lipid mixing.
      Not only can the device be used to record the dynamics of lipid membrane fusion,
      but it can be used for reaction monitoring by fusing GUVs containing reactants.
      We demonstrate this by fusing vesicles encapsulating femtolitre volumes of cobalt
      chloride or EDTA and monitoring the amount of the complexation product over time.

PMID- 24911346
TI  - Non-precious metals catalyze formal [4 + 2] cycloaddition reactions of 1,2
      diazines and siloxyalkynes under ambient conditions.
AB  - Copper(I) and nickel(0) complexes catalyze the formal [4 + 2] cycloaddition
      reactions of 1,2-diazines and siloxyalkynes, a reaction hitherto best catalyzed
      by silver salts. These catalysts based on earth abundant metals are not only
      competent, but the copper catalyst, in particular, promotes cycloadditions of
      pyrido[2,3-d]pyridazine and pyrido[3,4-d]pyridazine, enabling a new synthesis of
      quinoline and isoquinoline derivatives, as well as the formal [2 + 2]
      cycloaddition reaction of cyclohexenone with a siloxyalkyne. 

PMID- 24911347
TI  - Programmable patterning of protein bioactivity by visible light.
AB  - The simple and quick patterning of functional proteins on engineered surfaces
      affords an opportunity to fabricate protein microarrays in lab-on-chip systems.
      We report on the programmable patterning of proteins as well as the local
      activation of enzymes by visible light. We successfully generated functional
      protein patterns with different geometries in situ and demonstrated the specific
      patterning of multiple kinds of proteins side-by-side without the need for
      specific linker molecules or elaborate surface preparation. 

PMID- 24911348
TI  - Structure and activity of Streptococcus pyogenes SipA: a signal peptidase-like
      protein essential for pilus polymerisation.
AB  - The pili expressed on the surface of the human pathogen Streptococcus pyogenes
      play an important role in host cell attachment, colonisation and pathogenesis.
      These pili are built from two or three components, an adhesin subunit at the tip,
      a major pilin that forms a polymeric shaft, and a basal pilin that is attached to
      the cell wall. Assembly is carried out by specific sortase (cysteine
      transpeptidase) enzyme. These components are encoded in a small gene cluster
      within the S. pyogenes genome, often together with another protein, SipA, whose
      function is unknown. We show through functional assays, carried out by expressing
      the S. pyogenes pilus components in Lactococcus lactis, SipA from the clinically
      important M1T1 strain is essential for pilus assembly, and that SipA function is
      likely to be conserved in all S. pyogenes. From the crystal structure of SipA we
      confirm that SipA belongs to the family of bacterial signal peptidases (SPases),
      which process the signal-peptides of secreted proteins. In contrast to a previous
      arm-swapped SipA dimer, this present structure shows that its principal domain
      closely resembles the catalytic domain of SPases and has a very similar peptide
      binding cleft, but it lacks the catalytic Ser and Lys residues characteristic of
      SPases. In SipA these are replaced by Asp and Gly residues, which play no part in
      activity. We propose that SipA functions by binding a key component at the
      bacterial cell surface, in a conformation that facilitates pilus assembly. 

PMID- 24911351
TI  - CD8+/CD161++ mucosal-associated invariant T-cell levels in the colon are restored
      on long-term antiretroviral therapy and correlate with CD8+ T-cell immune
      activation.
AB  - Mucosal-associated invariant T (MAIT) cells are tissue-homing T cells recently
      implicated in HIV pathogenesis. We found that the proportion of MAIT cell in
      blood and colon of HIV+ patients are reduced in untreated infection.
      Antiretroviral therapy restored colonic but not blood MAIT cell percentages. We
      observed a negative correlation between colonic MAIT cells and T-cell activation
      in blood and suggest mucosal MAIT cell depletion may contribute to systemic
      immune activation in HIV infection. 

PMID- 24911350
TI  - HIV-1 superinfection with a triple-class drug-resistant strain in a patient
      successfully controlled with antiretroviral treatment.
AB  - We report a case of HIV-1 superinfection (HSI) with a clade B, triple-class
      resistant virus in a patient successfully controlling viremia with continuous
      combination antiretroviral therapy started 8 years earlier during primary HIV
      infection. The course of HIV infection prior to HSI was monitored in both the
      source partner and recipient (8 and 11 years, respectively) and 4 years following
      HSI. This case report demonstrates re-infection with HIV-1 despite effective
      combination antiretroviral therapy. 

PMID- 24911352
TI  - Polymorphism in interleukin-7 receptor alpha gene is associated with faster CD4+
      T-cell recovery after initiation of combination antiretroviral therapy.
AB  - OBJECTIVES: To investigate single-nucleotide polymorphisms (SNPs) in the gene
      encoding interleukin-7 receptor alpha (IL7RA) as predictors for CD4+ T-cell
      change after initiation of combination antiretroviral therapy (cART) in HIV
      infected whites. DESIGN: SNPs in IL7RA were determined in the Danish HIV Cohort
      Study. METHODS: CD4+ T-cell changes were estimated 6 months, 1, 2, and 5 years
      after initiation of cART in 1683 HIV-infected virally suppressed individuals.
      Five SNPs in IL7RA were examined as predictors for CD4+ T-cell change in the
      first (0-6 months after initiation of cART) and second phase (>6 months after
      initiation of cART) of immune recovery. Univariable and multivariable analyses
      including age, sex, calendar period, CD4+ nadir, and baseline CD4+ T-cell count
      and viral load as covariates were performed. RESULTS: Individuals carrying two T
      alleles in rs6897932 had faster CD4+ T-cell recovery compared with individuals
      carrying a C-allele in the first phase of immune recovery [mean CD4+ T-cell
      change, cells/MUL (95% confidence interval), in TT: 177 (151-203), CT: 131 (119
      143), CC: 141 (132-151), P = 0.018]. No isolated effect of rs6897932 on CD4+ T
      cell change was found in the second phase of immune recovery; however, the
      initial difference in CD4+ T-cell recovery remained during 5 years. The effect
      was most pronounced in individuals above 40 years of age. CONCLUSION: T-allele
      homozygosity in rs6897932 is a predictor for faster CD4+ T-cell recovery after
      initiation of cART in HIV-infected whites, however, only in the first phase of
      immune recovery.

PMID- 24911353
TI  - Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV
      infected adults on combination antiretroviral therapy: a phase I/II, randomized
      trial.
AB  - OBJECTIVE: Tuberculosis (TB) is highly prevalent among HIV-infected people,
      including those receiving combination antiretroviral therapy (cART),
      necessitating a well tolerated and efficacious TB vaccine for these populations.
      We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01
      in adults with well controlled HIV infection on cART. DESIGN: A randomized,
      observer-blind, controlled trial (NCT00707967). METHODS: HIV-infected adults on
      cART in Switzerland were randomized 3 : 1 : 1 to receive two doses, 1 month
      apart, of M72/AS01, AS01 or 0.9% physiological saline (N = 22, N = 8 and N = 7,
      respectively) and were followed up to 6 months postdose 2 (D210). Individuals
      with CD4+ cell counts below 200 cells/MUl were excluded. Adverse events (AEs)
      including HIV-specific and laboratory safety parameters were recorded. Cell
      mediated (ICS) and humoral (ELISA) responses were evaluated before vaccination, 1
      month after each dose (D30, D60) and D210. RESULTS: Thirty-seven individuals
      [interquartile range (IQR) CD4+ cell counts at screening: 438-872 cells/MUl;
      undetectable HIV-1 viremia] were enrolled; 73% of individuals reported previous
      BCG vaccination, 97.3% tested negative for the QuantiFERON-TB assay. For M72/AS01
      recipients, no vaccine-related serious AEs or cART-regimen adjustments were
      recorded, and there were no clinically relevant effects on laboratory safety
      parameters, HIV-1 viral loads or CD4+ cell counts. M72/AS01 was immunogenic,
      inducing persistent and polyfunctional M72-specific CD4+ T-cell responses
      [medians 0.70% (IQR 0.37-1.07) at D60] and 0.42% (0.24-0.61) at D210,
      predominantly CD40L+IL-2+TNF-alpha+, CD40L+IL-2+ and CD40L+IL-2+TNF-alpha+IFN
      gamma+]. All M72/AS01 vaccines were seropositive for anti-M72 IgG after second
      vaccination until study end. CONCLUSION: M72/AS01 was clinically well tolerated
      and immunogenic in this population, supporting further clinical evaluation in HIV
      infected individuals in TB-endemic settings.

PMID- 24911354
TI  - HLA Class I restricted CD8+ and Class II restricted CD4+ T cells are implicated
      in the pathogenesis of nevirapine hypersensitivity.
AB  - OBJECTIVES: This study sought to examine nevirapine hypersensitivity (NVP HSR)
      phenotypes and their relationship with differing major histocompatibility complex
      (MHC) Class I and Class II alleles and the associated CD4 and CD8 T-cell NVP
      specific responses and their durability over time. METHODS: A retrospective
      cohort study compared HIV-positive patients with NVP HSR, defined by fever and
      hepatitis and/or rash, with those tolerant of NVP for more than 3 months.
      Covariates included class I (HLA-A, B, C) and class II (HLA-DR) alleles. Cellular
      studies examined NVP-specific CD4 and CD8 T-cell responses by interferon-gamma
      (IFNgamma) ELISpot assay and intracellular cytokine staining (ICS). RESULTS: NVP
      HSR occurred in 19 out of 451 (4%) NVP-exposed individuals between March 1993 and
      December 2011. HLA associations were phenotype dependent with HLA-DRB1*01 : 01
      associated with hepatitis (P = 0.02); HLA-B*35 : 01 and HLA-Cw4 associated with
      cutaneous NVP HSR (P = 0.001, P = 0.01), and HLA-Cw*08 was associated with NVP
      HSR with eosinophilia (P = 0.04) and multisystemic NVP HSR (P = 0.02). NVP
      specific INFgamma responses waned significantly more than 3 months from the
      original reaction and were diminished or completely abrogated when either CD4 or
      CD8 T cells were depleted from the peripheral blood mononuclear cells culture.
      CONCLUSION: The association of specific class I and II allele pairings with
      specific phenotypes of NVP HSR, and cellular studies showing both CD4 and CD8 T
      cell NVP-specific responses suggest that specific combinations of NVP reactive
      class I restricted CD8 and class II restricted CD4 T cells contribute to the
      immunopathogenesis of NVP HSR.

PMID- 24911355
TI  - Buccal and sublingual vaccine delivery.
AB  - Because of their large surface area and immunological competence, mucosal tissues
      are attractive administration and target sites for vaccination. An important
      characteristic of mucosal vaccination is its ability to elicit local immune
      responses, which act against infection at the site of pathogen entry. However,
      mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms
      to prevent the immune system from overreacting to the many environmental
      antigens. Hence, mucosal vaccination may suppress the immune system instead of
      induce a protective immune response. Therefore, mucosal adjuvants and/or special
      antigen delivery systems as well as appropriate dosage forms are required in
      order to develop potent mucosal vaccines. Whereas oral, nasal and pulmonary
      vaccine delivery strategies have been described extensively, the sublingual and
      buccal routes have received considerably less attention. In this review, the
      characteristics of and approaches for sublingual and buccal vaccine delivery are
      described and compared with other mucosal vaccine delivery sites. We discuss
      recent progress and highlight promising developments in the search for vaccine
      formulations, including adjuvants and suitable dosage forms, which are likely
      critical for designing a successful sublingual or buccal vaccine. Finally, we
      outline the challenges, hurdles to overcome and formulation issues relevant for
      sublingual or buccal vaccine delivery. 

PMID- 24911356
TI  - The effect of a 3-month prevention program on the jump-landing technique in
      basketball: a randomized controlled trial.
AB  - CONTEXT: In jump-landing sports, the injury mechanism that most frequently
      results in an injury is the jump-landing movement. Influencing the movement
      patterns and biomechanical predisposing factors are supposed to decrease injury
      occurrence. OBJECTIVES: To evaluate the influence of a 3-mo coach-supervised jump
      landing prevention program on jump-landing technique using the jump-landing
      scoring (JLS) system. DESIGN: Randomized controlled trial. SETTING: On-field.
      PARTICIPANTS: 116 athletes age 15-41 y, with 63 athletes in the control group and
      53 athletes in the intervention group. INTERVENTION: The intervention program in
      this randomized control trial was administered at the start of the basketball
      season 2010-11. The jump-landing training program, supervised by the athletic
      trainers, was performed for a period of 3 mo. MAIN OUTCOME MEASURES: The jump
      landing technique was determined by registering the jump-landing technique of all
      athletes with the JLS system, pre- and postintervention. RESULTS: After the
      prevention program, the athletes of the male and female intervention groups
      landed with a significantly less erect position than those in the control groups
      (P < .05). This was presented by a significant improvement in maximal hip
      flexion, maximal knee flexion, hip active range of motion, and knee active range
      of motion. Another important finding was that postintervention, knee valgus
      during landing diminished significantly (P < .05) in the female intervention
      group compared with their control group. Furthermore, the male intervention group
      significantly improved (P < .05) the scores of the JLS system from pre- to
      postintervention. CONCLUSION: Malalignments such as valgus position and
      insufficient knee flexion and hip flexion, previously identified as possible risk
      factors for lower-extremity injuries, improved significantly after the completion
      of the prevention program. The JLS system can help in identifying these
      malalignments. LEVEL OF EVIDENCE: Therapy, prevention, level 1b.

PMID- 24911357
TI  - One-electron-mediated rearrangements of 2,3-disiladicarbene.
AB  - A disiladicarbene, (Cy-cAAC)2Si2 (2), was synthesized by reduction of Cy
      cAAC:SiCl4 adduct with KC8. The dark-colored compound 2 is stable at room
      temperature for a year under an inert atmosphere. Moreover, it is stable up to
      190  degrees C and also can be characterized by electron ionization mass
      spectrometry. Theoretical and Raman studies reveal the existence of a Si?Si
      double bond with a partial double bond between each carbene carbon atom and
      silicon atom. Cyclic voltammetry suggests that 2 can quasi-reversibly accept an
      electron to produce a very reactive radical anion, 2(*-), as an intermediate
      species. Thus, reduction of 2 with potassium metal at room temperature led to the
      isolation of an isomeric neutral rearranged product and an anionic dimer of a
      potassium salt via the formation of 2(*-). 

PMID- 24911358
TI  - Active surveillance of the trachea or throat for MRSA is more sensitive than
      nasal surveillance and a better predictor of MRSA infections among patients in
      intensive care.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most
      common causes of infection in the intensive care unit (ICU). Although
      surveillance culture for MRSA is recommended for ICU patients, no comparative
      study investigating the optimal sites and frequency of culture has been performed
      in this population. METHODS: A prospective observational cohort study was
      performed in an 18-bed emergency intensive care unit (EICU) in a tertiary
      teaching hospital. A total of 282 patients were included. Samples for MRSA
      detection were obtained at the time of admission, 48 h after admission, and then
      weekly thereafter. All subjects were routinely monitored for the development of
      MRSA infection during their stay in the ICU. RESULTS: MRSA colonization was
      detected in 129 (46%) patients over the course of the study. The sensitivity of
      MRSA surveillance culture was significantly higher in throat or tracheal
      aspirates (82%; 106/129) than in anterior nares (47%; 61/129) (P<0.001). The
      sensitivity of MRSA surveillance culture for subsequent MRSA infection and MRSA
      pneumonia was also higher in the throat/trachea (69 and 93%, respectively) than
      in the anterior nares (48 and 50%, respectively). The area under the curve for
      subsequent MRSA infection was higher in trachea/throat (0.675) than in the
      anterior nares (0.648); however, this difference was not significant (P>0.05).
      The area under the curve for MRSA pneumonia was significantly higher in
      trachea/throat (0.791; 95% CI, 0.739-0.837) than anterior nares (0.649; 95% CI,
      0.590-0.705) (P = 0.044). CONCLUSION: MRSA colonization was more common in the
      trachea/throat than in the anterior nares in ICU patients. Cultures from throat
      or tracheal aspirates were more sensitive and predictive of subsequent MRSA
      pneumonia than cultures from the anterior nares in this population.

PMID- 24911360
TI  - Morphology, structure and function characterization of PEI modified magnetic
      nanoparticles gene delivery system.
AB  - Modified magnetic nanoparticles are used as non-viral gene carriers in biological
      applications. To achieve successful gene delivery, it is critical that
      nanoparticles effectually assemble with nucleic acids. However, relatively little
      work has been conducted on the assemble mechanisms between nanoparticles and DNA,
      and its effects on transfection efficiency. Using biophysical and biochemical
      characterization, along with Atomic force microscopy (AFM) and Transmission
      electron microscopy (TEM), we investigate the morphologies, assembling structures
      and gene delivering abilities of the PEI modified magnetic nanoparticles (MNPs)
      gene delivery system. In this gene delivery system, MNP/DNA complexes are formed
      via binding of DNA onto the surface of MNPs. MNPs are favorable to not only
      increase DNA concentration but also prevent DNA degradation. Magnetofection
      experiments showed that MNPs has low cytotoxicity and introduces highly stable
      transfection in mammalian somatic cells. In addition, different binding ratios
      between MNPs and DNA result in various morphologies of MNP/DNA complexes and have
      an influence on transfection efficiency. Dose-response profile indicated that
      transfection efficiency positively correlate with MNP/DNA ratio. Furthermore,
      intracellular tracking demonstrate that MNPs move though the cell membranes,
      deliver and release exogenous DNA into the nucleus. 

PMID- 24911359
TI  - Persistent organic pollutants and inflammatory markers in a cross-sectional study
      of elderly Swedish people: the PIVUS cohort.
AB  - BACKGROUND: Persistent organic pollutants (POPs) are compounds that are generated
      through various industrial activities and released in the surrounding
      environment. Different animal studies have shown effects of different POPs on
      various inflammatory markers. OBJECTIVE: Because very few studies have been
      conducted in humans, we assessed the associations between different POPs and
      inflammatory markers in a large population-based sample of elderly men and women
      (all 70 years of age) from Sweden. METHODS: This cross-sectional study
      investigated the concentrations of several polychlorinated biphenyls (PCBs),
      organochlorine pesticides, polychlorinated dibenzo-p-dioxin, and brominated
      diphenyl ether congeners and their association with a number of inflammatory
      markers [vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion
      molecule 1 (ICAM-1), E-selectin, C-reactive protein (CRP), total leucocyte count,
      tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1),
      and interleukin 6 (IL-6)] in 992 individuals. These individuals were recruited
      from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)
      cohort. We used a total toxic equivalency (TEQ) value that measures toxicological
      effects with the relative potencies of various POPs. RESULTS: Following
      adjustment for potential confounders, the TEQ value (driven mainly by PCB-126)
      was significantly associated with levels of ICAM-1 (p < 10-5). A similar trend
      was also observed between sum of PCBs and VCAM-1 (p < 0.001). No significant
      associations were observed between levels of POPs and other inflammatory markers.
      CONCLUSIONS: TEQ values were associated with levels of ICAM-1, to a lesser degree
      also with VCAM-1, but not with CRP and several other inflammatory markers. These
      findings suggest an activation of vascular adhesion molecules by POPs, and
      particularly by PCB-126.

PMID- 24911361
TI  - Biomechanics and thermodynamics of nanoparticle interactions with plasma and
      endosomal membrane lipids in cellular uptake and endosomal escape.
AB  - To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs)
      taken up via endocytic pathways must efficiently transport across the cell
      membrane and subsequently escape from the secondary endosomes. We hypothesized
      that the biomechanical and thermodynamic interactions of NPs with plasma and
      endosomal membrane lipids are involved in these processes. Using model plasma and
      endosomal lipid membranes, we compared the interactions of cationic NPs composed
      of poly(D,L-lactide-co-glycolide) modified with the dichain surfactant
      didodecyldimethylammonium bromide (DMAB) or the single-chain surfactant
      cetyltrimethylammonium bromide (CTAB) vs anionic unmodified NPs of similar size.
      We validated our hypothesis in doxorubicin-sensitive (MCF-7, with relatively
      fluid membranes) and resistant breast cancer cells (MCF-7/ADR, with rigid
      membranes). Despite their cationic surface charges, DMAB- and CTAB-modified NPs
      showed different patterns of biophysical interaction: DMAB-modified NPs induced
      bending of the model plasma membrane, whereas CTAB-modified NPs condensed the
      membrane, thereby resisted bending. Unmodified NPs showed no effects on bending.
      DMAB-modified NPs also induced thermodynamic instability of the model endosomal
      membrane, whereas CTAB-modified and unmodified NPs had no effect. Since bending
      of the plasma membrane and destabilization of the endosomal membrane are critical
      biophysical processes in NP cellular uptake and endosomal escape, respectively,
      we tested these NPs for cellular uptake and drug efficacy. Confocal imaging
      showed that in both sensitive and resistant cells DMAB-modified NPs exhibited
      greater cellular uptake and escape from endosomes than CTAB-modified or
      unmodified NPs. Further, paclitaxel-loaded DMAB-modified NPs induced greater
      cytotoxicity even in resistant cells than CTAB-modified or unmodified NPs or drug
      in solution, demonstrating the potential of DMAB-modified NPs to overcome the
      transport barrier in resistant cells. In conclusion, biomechanical interactions
      with membrane lipids are involved in cellular uptake and endosomal escape of NPs.
      Biophysical interaction studies could help us better understand the role of
      membrane lipids in cellular uptake and intracellular trafficking of NPs.

PMID- 24911362
TI  - Kaposi's sarcoma-associated herpesvirus ORF6 gene is essential in viral lytic
      replication.
AB  - Kaposi's sarcoma associated herpesvirus (KSHV) is associated with Kaposis's
      sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease.
      KSHV encodes at least 8 open reading frames (ORFs) that play important roles in
      its lytic DNA replication. Among which, ORF6 of KSHV encodes an ssDNA binding
      protein that has been proved to participate in origin-dependent DNA replication
      in transient assays. To define further the function of ORF6 in the virus life
      cycle, we constructed a recombinant virus genome with a large deletion within the
      ORF6 locus by using a bacterial artificial chromosome (BAC) system. Stable 293T
      cells carrying the BAC36 (wild type) and BACDelta6 genomes were generated. When
      monolayers of 293T-BAC36 and 293T-BACDelta6 cells were induced with 12-O
      tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate, infectious virus was
      detected from the 293T-BAC36 cell supernatants only and not from the 293T-
      BACDelta6 cell supernatants. DNA synthesis was defective in 293T-BACDelta6 cells.
      Expression of ORF6 in trans in BACDelta6-containing cells was able to rescue both
      defects. Our results provide genetic evidence that ORF6 is essential for KSHV
      lytic replication. The stable 293T cells carrying the BAC36 and BACDelta6 genomes
      could be used as tools to investigate the detailed functions of ORF6 in the lytic
      replication of KSHV. 

PMID- 24911364
TI  - Biopsy-proven recurrence of unilateral IgG4-related orbital inflammation after 20
      years.
AB  - A 38-year-old female patient presented with a painful swelling in the lateral
      part of the upper eyelid, a diffuse scleritis and slight hypoglobus of the right
      eye. An orbital biopsy showed a fibrotic idiopathic orbital inflammation (IOI)
      with, on immunohistochemical staining, an increased number of IgG4-positive
      plasma cells scored as >200 per high-power field, with IgG4/IgG ratio >0.50,
      indicating orbital IgG4 related autoimmune disease. On treatment with oral
      prednisone and azathioprine the symptoms resolved within 6 months. Twenty years
      prior, the patient had been diagnosed with an IOI of at the same side, for which
      at that time a biopsy had been taken similarly. Reclassification of the previous
      biopsy specimen with immunohistological staining also showed evidence of orbital
      IgG4 related disease. To our knowledge this is the first report of a biopsy
      proven unilateral IgG4-related orbitopathy that recurred after 20 years.

PMID- 24911363
TI  - Comparative chloroplast genomes of photosynthetic orchids: insights into
      evolution of the Orchidaceae and development of molecular markers for
      phylogenetic applications.
AB  - The orchid family Orchidaceae is one of the largest angiosperm families,
      including many species of important economic value. While chloroplast genomes are
      very informative for systematics and species identification, there is very
      limited information available on chloroplast genomes in the Orchidaceae. Here, we
      report the complete chloroplast genomes of the medicinal plant Dendrobium
      officinale and the ornamental orchid Cypripedium macranthos, demonstrating their
      gene content and order and potential RNA editing sites. The chloroplast genomes
      of the above two species and five known photosynthetic orchids showed
      similarities in structure as well as gene order and content, but differences in
      the organization of the inverted repeat/small single-copy junction and ndh genes.
      The organization of the inverted repeat/small single-copy junctions in the
      chloroplast genomes of these orchids was classified into four types; we propose
      that inverted repeats flanking the small single-copy region underwent expansion
      or contraction among Orchidaceae. The AT-rich regions of the ycf1 gene in orchids
      could be linked to the recombination of inverted repeat/small single-copy
      junctions. Relative species in orchids displayed similar patterns of variation in
      ndh gene contents. Furthermore, fifteen highly divergent protein-coding genes
      were identified, which are useful for phylogenetic analyses in orchids. To test
      the efficiency of these genes serving as markers in phylogenetic analyses, coding
      regions of four genes (accD, ccsA, matK, and ycf1) were used as a case study to
      construct phylogenetic trees in the subfamily Epidendroideae. High support was
      obtained for placement of previously unlocated subtribes Collabiinae and
      Dendrobiinae in the subfamily Epidendroideae. Our findings expand understanding
      of the diversity of orchid chloroplast genomes and provide a reference for study
      of the molecular systematics of this family. 

PMID- 24911365
TI  - Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic
      sheep model.
AB  - OBJECTIVES: In this study, Adipose stem cells (ADSC) and bone marrow stem cells
      (BMSC), multipotent adult cells with the potentials for cartilage regenerations
      were induced to chondrogenic lineage and used for cartilage regenerations in
      surgically induced osteoarthritis in sheep model. METHODS: Osteoarthritis was
      induced at the right knee of sheep by complete resection of the anterior cruciate
      ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells
      from experimental sheep were culture expanded and induced to chondrogenic
      lineage. Test sheep received a single dose of 2 * 10(7) autologous PKH26
      labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while
      controls received 5 mls culture medium. RESULTS: The proliferation rate of ADSCs
      34.4 +/- 1.6 hr was significantly higher than that of the BMSCs 48.8 +/- 5.3 hr
      (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of
      chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to
      chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints
      showed regenerated de novo cartilages within 6 weeks post-treatment. On the
      International Cartilage Repair Society grade scores, chondrogenically induced
      ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001
      and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells
      showed that they had populated the damaged area of cartilage. Histological
      staining revealed loosely packed matrixes of de novo cartilages and
      immunostaining demonstrated the presence of cartilage specific proteins, Collagen
      II and SOX9. CONCLUSION: Autologous chondrogenically induced ADSCs and BMSCs
      could be promising cell sources for cartilage regeneration in osteoarthritis.

PMID- 24911366
TI  - Analysis of candidate genes for lineage-specific expression changes in humans and
      primates.
AB  - RUNX2, a gene involved in skeletal development, has previously been shown to be
      potentially affected by positive selection during recent human evolution. Here we
      have used antibody-based proteomics to characterize potential differences in
      expression patterns of RUNX2 interacting partners during primate evolution.
      Tissue microarrays consisting of a large set of normal tissues from human and
      macaque were used for protein profiling of 50 RUNX2 partners with
      immunohistochemistry. Eleven proteins (AR, CREBBP, EP300, FGF2, HDAC3, JUN,
      PRKD3, RUNX1, SATB2, TCF3, and YAP1) showed differences in expression between
      humans and macaques. These proteins were further profiled in tissues from
      chimpanzee, gorilla, and orangutan, and the corresponding genes were analyzed
      with regard to genomic features. Moreover, protein expression data were compared
      with previously obtained RNA sequencing data from six different organs. One gene
      (TCF3) showed significant expression differences between human and macaque at
      both the protein and RNA level, with higher expression in a subset of germ cells
      in human testis compared with macaque. In conclusion, normal tissues from macaque
      and human showed differences in expression of some RUNX2 partners that could be
      mapped to various defined cell types. The applied strategy appears advantageous
      to characterize the consequences of altered genes selected during evolution. 

PMID- 24911367
TI  - Core self-evaluations mediate the associations of dispositional optimism and life
      satisfaction.
AB  - BACKGROUND: Positive traits, such as life satisfaction, optimism, and core self
      evaluation (CSE), have garnered increasing attention from researchers and
      professionals. However, the trilateral relationship among them remains unclear.
      OBJECTIVE: This study examines the effect of dispositional optimism on life
      satisfaction and primarily verified the mediator role of CSEs. METHODS: Six
      hundred thirty college students from two general universities completed a
      questionnaire packet containing life orientation test-revised (LOT-R), core self
      evaluations, and satisfaction with life scale. Confirmatory factor analysis (CFA)
      was conducted to assess the dimension of LOT-R. Bootstrap was used in structural
      equation modeling to analyze mediation effect. RESULTS: Results revealed that
      dispositional optimism and core self-evaluations were significantly correlated
      with life satisfaction. CFA identified the bidimensional structure of
      dispositional optimism. SEM indicated that core self-evaluations partially
      mediated the effect of dispositional optimism on life satisfaction. The final
      model also revealed significant paths from optimism and pessimism to life
      satisfaction through core-self evaluations. CONCLUSION: The findings extended
      prior studies and shed light on how dispositional optimism influences life
      satisfaction. This study provides valuable evidence on how to promote the life
      satisfaction of human beings in positive psychology. A further study can fully
      explore the relationship among them in multi-cultural follow-up studies.

PMID- 24911369
TI  - Efficacy of a triple antiemetic regimen with aprepitant for the prevention of
      chemotherapy-induced nausea and vomiting: effects of gender, age, and region.
AB  - OBJECTIVE: To determine the variability in treatment responses to antiemetic
      therapy (ondansetron and dexamethasone vs ondansetron and dexamethasone plus
      aprepitant) given with moderately emetogenic chemotherapy. RESEARCH DESIGN AND
      METHODS: Post hoc subgroup analysis of data from a phase III, randomized, double
      blind clinical trial evaluated whether the efficacy of aprepitant triple therapy
      (ondansetron and dexamethasone plus aprepitant) versus control (ondansetron and
      dexamethasone) varies by gender, age, or region in 848 men and women >=18 years
      old with histologically confirmed malignancies and who were naive to moderately
      or highly emetogenic chemotherapeutic agents. Endpoints compared were the
      incidences of no vomiting, complete response, and no use of rescue therapy, all
      during the overall period (0-120 h). MAIN OUTCOME MEASURES: Regardless of age,
      gender, or region, the aprepitant regimen provided better control for the no
      vomiting and complete-response (no vomiting, no rescue therapy) endpoints.
      RESULTS: The aprepitant regimen provided better control for the no-vomiting and
      complete-response (no vomiting, no rescue therapy) endpoints. Overall response
      rates were higher in men and in older (>=55 y) patients, but treatment
      differences were greater among women and younger patients, known to be at
      increased chemotherapy-induced nausea and vomiting (CINV) risk. Aprepitant showed
      a benefit versus control across regions, although the between-treatment
      difference appeared to be smaller for patients in Central/South America versus
      North America or international regions. CONCLUSIONS: Although we acknowledge that
      subset numbers in this post hoc analysis may be too small to allow definitive
      conclusions, the data suggest that aprepitant triple therapy provides a benefit
      over control therapy for the prevention of CINV in patients receiving
      anthracycline and cyclophosphamide (AC)- or non-AC-based moderately emetogenic
      chemotherapy across age, gender, and region. (Original trial results available at
      ClinicalTrials.gov: NCT00337727.).

PMID- 24911370
TI  - Growth losses in Swiss forests caused by ozone: epidemiological data analysis of
      stem increment of Fagus sylvatica L. and Picea abies Karst.
AB  - The estimate of growth losses by ozone exposure of forest trees is a significant
      part in current C sequestration calculations and will also be important in future
      modeling. It is therefore important to know if the relationship between ozone
      flux and growth reduction of young trees, used to derive a Critical Level for
      ozone, is also valid for mature trees. Epidemiological analysis of stem increment
      data from Fagus sylvatica L. and Picea abies Karst. observed in Swiss forest
      plots was used to test this hypothesis. The results confirm the validity of the
      flux-response relationship at least for beech and therefore enable estimating
      forest growth losses by ozone on a country-wide scale. For Switzerland, these
      estimates amount to 19.5% growth reduction for deciduous forests, 6.6% for
      coniferous forests and 11.0% for all forested areas based on annual ozone
      stomatal uptake during the time period 1991-2011. 

PMID- 24911368
TI  - Retreatment with varenicline for smoking cessation in smokers who have previously
      taken varenicline: a randomized, placebo-controlled trial.
AB  - The efficacy and safety of retreatment with varenicline in smokers attempting to
      quit were evaluated in this randomized, double-blind, placebo-controlled,
      multicenter trial (Australia, Belgium, Canada, the Czech Republic, France,
      Germany, the United Kingdom, and the United States). Participants were generally
      healthy adult smokers (>= 10 cigarettes/day) with >= 1 prior quit attempt (>= 2
      weeks) using varenicline and no quit attempts in <= 3 months; they were randomly
      assigned (1:1) to 12 weeks' varenicline (n = 251) or placebo (n = 247) treatment,
      with individual counseling, plus 40 weeks' nontreatment follow-up. The primary
      efficacy end point was the carbon monoxide-confirmed (<= 10 ppm) continuous
      abstinence rate for weeks 9-12, which was 45.0% (varenicline; n = 249) vs. 11.8%
      (placebo; n = 245; odds ratio: 7.08; 95% confidence interval: 4.34, 11.55; P <
      0.0001). Common varenicline group adverse events were nausea, abnormal dreams,
      and headache, with no reported suicidal behavior. Varenicline is efficacious and
      well tolerated in smokers who have previously taken it. Abstinence rates are
      comparable with rates reported for varenicline-naive smokers.

PMID- 24911371
TI  - Improving patient outcomes through advanced pain management techniques in total
      hip and knee arthroplasty.
AB  - Pain following orthopedic surgery is common and often suboptimally managed, with
      many patients reporting acute moderate to severe pain following surgery. Opioids
      are often used to manage this pain, yet this can result in significant side
      effects and complications, including constipation, nausea, vomiting, respiratory
      distress, and other central nervous system issues. Multimodal therapy that
      includes surgical site infiltration with extended release local anesthetic has
      been seen as a new way to minimize this pain for patients, which can result in
      improved quality of life and shorter length of hospital stay. This article
      examines the use of bupivacaine liposome injectable suspension (EXPAREL(r);
      Pacira Pharmaceuticals, Inc., San Diego, California), a non-opioid product for
      pain management. Liposomal bupivacaine uses DepoFoam(r) technology that allows
      for the extended release of injected drugs. When used as the foundation of a
      multimodal regimen, it is effective in reducing postsurgical pain for up to 72
      hours while reducing the need for opioids for pain relief. 

PMID- 24911372
TI  - miR-185 inhibits hepatocellular carcinoma growth by targeting the DNMT1/PTEN/Akt
      pathway.
AB  - miRNAs have recently been implicated in hepatocarcinogenesis, although the
      actions and mechanisms of individual miRNAs remain incompletely understood. We
      examined the biological functions and molecular mechanisms of miR-185 in
      hepatocellular carcinoma (HCC). The expression of miR-185 is decreased in human
      HCC tissues compared with the nonneoplastic liver parenchyma. Quantitative RT-PCR
      showed a reduction of miR-185 in human HCC cells compared with primary
      hepatocytes. miR-185 overexpression in human HCC cells inhibited cell
      proliferation and invasion in vitro and prevented tumor growth in SCID mice. miR
      185 overexpression inhibited DNMT1 3' untranslated region luciferase reporter
      activity in HCC cells; this effect was abolished when the miR-185 binding site
      was mutated. miR-185 mimic or overexpression decreased the level of DNMT1 protein
      in HCC cells. These findings establish DNMT1 as a bona fide target of miR-185 in
      HCC cells. The role of DNMT1 in miR-185-induced inhibition of HCC growth was
      further supported by the fact that DNMT1 overexpression prevented miR-185-induced
      inhibition of HCC cell proliferation/invasion. miR-185 mimic or overexpression
      reduced PTEN promoter DNA methylation and enhanced PTEN expression, leading to
      the inhibition of Akt phosphorylation; these effects were partially reversed by
      DNMT1 overexpression. These results provide novel evidence that miR-185 inhibits
      HCC cell growth by targeting DNMT1, leading to PTEN induction and Akt inhibition.
      Thus, reactivation or induction of miR-185 may represent a novel therapeutic
      strategy for HCC treatment. 

PMID- 24911374
TI  - Clinical importance of toxin concentration in Amanita verna mushroom.
AB  - Poisoning from Amanita group of mushrooms comprises approximately 3% of all
      poisonings in our country and their being responsible for nearly the entire fatal
      mushroom poisonings makes them important. These mushrooms contain primarily two
      types of toxins, amatoxins and phallotoxins. Phallotoxins have a more limited
      toxicity potential and they primarily consist of phalloidin (PHN) and phallacidin
      (PCN). Amatoxins, on the other hand, are very toxic and they primarily consist of
      alpha-amanitin (AA), beta-amanitin (BA) and gamma-amanitin (GA). Toxin levels can
      vary among various species, even among varieties of the same species, of Amanita
      mushroom family. Revealing the differences between the toxin compositions of the
      Amanita species that grow in our region may contribute to the clinics of
      poisonings. Our study aims at showing in detail the toxin levels in various parts
      of Amanita verna mushroom. A. verna mushrooms needed for toxin analysis were
      collected from Kozak Plateau near Ayvalik county of Balikesir, Turkey in April
      2013. The mushrooms were divided into their parts as pileus, gills, stripe and
      volva. Following the procedures required before the analysis, the AA, BA, GA, PHN
      and PCN levels were measured using the RP-HPLC method. While the lowest level of
      amatoxin was in the volva of the mushroom, the highest was measured in the gills.
      This was followed by pileus and stripe where the levels were close to each other.
      Similarly, the highest level of phallotoxin was measured in the gills. Gamma
      toxin and phalloidin were at lower amounts than the other toxins. A. verna is
      frequently confused with edible mushrooms with white caps due to its macroscopic
      similarity. If just one of them is eaten by mistake by an adult person with no
      mushroom experience, it can easily poison them. The amount of amatoxin is more as
      compared to Amanita phalloides and A. phalloides var. alba. Particularly, the AA
      and BA levels are approximately three times higher, whereas GA levels are lower.
      Similarly, the level of PCN is approximately four times higher as compared to A.
      phalloides and A. phalloides var. alba; by contrast, the level of PNH is about a
      half of theirs. In summary, it can be said that A. verna is a more toxic mushroom
      than A. phalloides and has a higher rate of mortality. With our study, the
      amatoxin and phallotoxin concentrations and distribution in A. verna mushrooms
      were shown in detail for the first time and it would be useful to carry out more
      similar studies with other members of Amanita family growing in various parts of
      the world. 

PMID- 24911375
TI  - Functional assessment of toad parotoid macroglands: a study based on poison
      replacement after mechanical compression.
AB  - Toads have a pair of parotoid macroglands behind the eyes that secrete poison
      used in passive defence against predators. These macroglands are composed of
      juxtaposed alveoli, each one bearing a syncytial gland, all connected to the
      exterior by ducts. When the parotoids are bitten, the poison is expelled on the
      predator oral mucosa in the form of jets, causing several pharmacological
      actions. After poison release, the empty secretory syncytia immediately collapse
      in the interior of their respective alveoli and gradually start refilling. After
      parotoid manual compression, simulating a predator's bite, we studied, by means
      of morphological methods, the replacement of the poison inside the alveoli. The
      results showed that after compression, a considerable number of alveoli remained
      intact. In the alveoli that were effectively affected the recovery occurs in
      different levels, from total to punctual and often restrict to some areas of the
      syncytia. The severely affected alveoli seem not recover their original
      functional state. The fact that only a part of the parotoid alveoli is compressed
      during an attack seems to be crucial for toad survival, since the amphibian,
      after being bitten by a predator, do not lose all its poison stock, remaining
      protected in case of new attacks. 

PMID- 24911373
TI  - Commensal bacterial endocytosis in epithelial cells is dependent on myosin light
      chain kinase-activated brush border fanning by interferon-gamma.
AB  - Abnormal bacterial adherence and internalization in enterocytes have been
      documented in Crohn disease, celiac disease, surgical stress, and intestinal
      obstruction and are associated with low-level interferon (IFN)-gamma production.
      How commensals gain access to epithelial soma through densely packed microvilli
      rooted on the terminal web (TW) remains unclear. We investigated molecular and
      ultrastructural mechanisms of bacterial endocytosis, focusing on regulatory roles
      of IFN-gamma and myosin light chain kinase (MLCK) in TW myosin phosphorylation
      and brush border fanning. Mouse intestines were sham operated on or obstructed
      for 6 hours by loop ligation with intraluminally administered ML-7 (a MLCK
      inhibitor) or Y27632 (a Rho-associated kinase inhibitor). After intestinal
      obstruction, epithelial endocytosis and extraintestinal translocation of bacteria
      were observed in the absence of tight junctional damage. Enhanced TW myosin light
      chain phosphorylation, arc formation, and brush border fanning coincided with
      intermicrovillous bacterial penetration, which were inhibited by ML-7 and
      neutralizing anti-IFN-gamma but not Y27632. The phenomena were not seen in mice
      genetically deficient for long MLCK-210 or IFN-gamma. Stimulation of human Caco
      2BBe cells with IFN-gamma caused MLCK-dependent TW arc formation and brush border
      fanning, which preceded caveolin-mediated bacterial internalization through
      cholesterol-rich lipid rafts. In conclusion, epithelial MLCK-activated brush
      border fanning by IFN-gamma promotes adherence and internalization of normally
      noninvasive enteric bacteria. Transcytotic commensal penetration may contribute
      to initiation or relapse of chronic inflammation. 

PMID- 24911376
TI  - Single-task fMRI overlap predicts concurrent multitasking interference.
AB  - There is no consensus regarding the origin of behavioral interference that occurs
      during concurrent multitasking. Some evidence points toward a multitasking locus
      in the brain, while other results imply that interference is the consequence of
      task interactions in several brain regions. To investigate this issue, we
      conducted a functional MRI (fMRI) study consisting of three component tasks,
      which were performed both separately and in combination. The results indicated
      that no specific multitasking area exists. Instead, different patterns of
      activation across conditions could be explained by assuming that the interference
      is a result of task interactions. Additionally, similarity in single-task
      activation patterns correlated with a decrease in accuracy during dual-task
      conditions. Taken together, these results support the view that multitasking
      interference is not due to a bottleneck in a single "multitasking" brain region,
      but is a result of interactions between concurrently running processes. 

PMID- 24911378
TI  - Pregnancy outcome of overweight and obese Chinese women with gestational
      diabetes.
AB  - We investigated the pregnancy outcome of overweight and obese Chinese women with
      gestational diabetes mellitus (GDM). Patients diagnosed as GDM from January 2010
      to December 2011 were categorised into three groups, as normal weight, overweight
      and obese, according to the maternal pre-pregnancy body mass index (BMI)
      (kg/m(2)), 18.5-24.9, 25-29.9 and >= 30, respectively. Of the 604 GDM cases, 241
      (39.9%), 211 (34.9%) and 152 (25.2%) subjects were normal weight, overweight and
      obese, respectively. Compared with subjects of normal weight, the incidence of
      assisted reproductive technology (ART) pregnancy, advanced maternal age, fetal
      macrosomia and emergency caesarean delivery were significantly higher in
      overweight and obese groups (p < 0.05). Obese women were at increased risk of
      premature rupture of membranes, pre-eclampsia and caesarean section compared with
      the other two groups (p < 0.05). Overweight and obese women with GDM have an
      increased risk of adverse pregnancy outcomes, even with good glycaemic control.

PMID- 24911377
TI  - A novel matrix-similarity based loss function for joint regression and
      classification in AD diagnosis.
AB  - Recent studies on AD/MCI diagnosis have shown that the tasks of identifying brain
      disease and predicting clinical scores are highly related to each other.
      Furthermore, it has been shown that feature selection with a manifold learning or
      a sparse model can handle the problems of high feature dimensionality and small
      sample size. However, the tasks of clinical score regression and clinical label
      classification were often conducted separately in the previous studies. Regarding
      the feature selection, to our best knowledge, most of the previous work
      considered a loss function defined as an element-wise difference between the
      target values and the predicted ones. In this paper, we consider the problems of
      joint regression and classification for AD/MCI diagnosis and propose a novel
      matrix-similarity based loss function that uses high-level information inherent
      in the target response matrix and imposes the information to be preserved in the
      predicted response matrix. The newly devised loss function is combined with a
      group lasso method for joint feature selection across tasks, i.e., predictions of
      clinical scores and a class label. In order to validate the effectiveness of the
      proposed method, we conducted experiments on the Alzheimer's Disease Neuroimaging
      Initiative (ADNI) dataset, and showed that the newly devised loss function helped
      enhance the performances of both clinical score prediction and disease status
      identification, outperforming the state-of-the-art methods. 

PMID- 24911379
TI  - Screening for novel risk factors related to peripherally inserted central
      catheter-associated complications.
AB  - BACKGROUND: Peripherally inserted central catheters (PICCs) are increasingly
      utilized. Patient and system factors that increase risk of complications should
      be identified to avoid preventable patient harm. METHODS: A case control analysis
      of adult inpatients who underwent PICC placement from January 2009 to January
      2010 at Scott & White Memorial Hospital was conducted to determine the incidence
      and risk factors for complications. One hundred seventy cases of inpatients who
      experienced PICC-related complications were identified. Age- and gender-matched
      controls were randomly selected among patients who underwent PICC placement
      without documented complications during this time. RESULTS: A total of 1444 PICCs
      were placed, with a complication rate of 11.77% (95% confidence interval: 10.11%
      13.44%). Complications included catheter-associated thrombosis (3%), mechanical
      complications (4%), catheter-associated bloodstream infections (2%), and
      cellulitis (1%). In multivariable logistic regression analyses, malnutrition and
      after-hours placement were significantly associated with increased risk of
      complications, as was body mass index (BMI) >30 after adjusting for
      anticoagulation and time of placement. In a secondary multivariable logistic
      regression analysis, after-hours placement and malnutrition were significantly
      associated with increased risk of nonmechanical complications. Additionally, in
      conditional univariate analyses, length of stay, malnutrition, and after-hours
      placement were associated with increased risk of catheter-associated thrombosis.
      In our multivariable logistic regression analyses, use of
      anticoagulation/antiplatelet agents was associated with decreased risk of all
      cause complications, nonmechanical complications, and catheter-associated
      thrombosis. CONCLUSIONS: Screening of patients undergoing PICC placement with
      attention to malnutrition, BMI >30, and length of stay may reduce the risk of
      PICC-associated complications. Use of anticoagulation/antiplatelet agents and
      avoiding after-hours placement may reduce complications and enhance patient
      safety.

PMID- 24911380
TI  - Metabolism and disposition of [(14)C]tivantinib after oral administration to
      humans, dogs and rats.
AB  - 1. The biotransformation and disposition of tivantinib in humans, dogs and rats
      was examined after a single oral administration of [(14)C]tivantinib. Tivantinib
      constituted no more than one-third of the plasma radioactivity in all species,
      demonstrating significant contribution of the metabolites to plasma
      radioactivity. The major circulating metabolites in all species were M4 and M5,
      hydroxylated metabolites at the benzyl position of the tricyclic ring, accounting
      for 19.3 and 12.2% of the AUC of the total radioactivity, respectively, in
      humans. 2. The majority of radioactivity was excreted to the feces via bile.
      Tivantinib was detected at trace levels in urine, feces and bile, demonstrating
      extensive metabolism prior to biliary excretion and nearly complete tivantinib
      absorption under fed conditions. 3. Seven metabolic pathways were identified for
      tivantinib and included six oxidations (M4, M5, M7, M8, M9 and M11) and one
      glucuronidation (M23). The major metabolic and excretory pathways were found to
      be common among all species. Species differences in the metabolic pathways
      included lactam metabolite (M8) formation in humans and dehydrogenated metabolite
      (M11) formation in animals. 4. None of the metabolites identified in this work
      are believed to significantly impact the efficacy or toxicity of tivantinib in
      humans.

PMID- 24911381
TI  - Template CoMFA applied to 116 biological targets.
AB  - Statistically acceptable 3D-QSAR models were effortlessly obtained, by
      application of automatic template CoMFA, for the vast majority, arguably more
      than 95%, of 116 biological targets. Among these targets, 76 were structure
      based, pooling multiple templates (as protein-bound conformation of ligands) and
      training sets into a single model, and the other 40 were ligand-based, with a low
      energy conformation of an exemplar training set structure becoming the single
      template. Criteria proposed for statistical acceptability are a leave-one-out
      q(2) > 0.4, or a standard error of leave-one-out prediction <1.0, or a ratio of
      best-fit r(2) to count of PLS components >0.2. The structure-based 3D-QSAR models
      provide direct visual comparisons of SAR-derived 3D-QSAR contours with cavity
      surfaces. 

PMID- 24911382
TI  - GC skew and mitochondrial origins of replication.
AB  - The comprehensive understanding of mitochondrial genome evolution requires a
      detailed mechanistic picture of mitogenomic replication. Despite many previous
      efforts it has remained a non-trivial problem to determine the origins of
      replication and trace their fate across rearrangements of the gene order even in
      the small genomes of animal mitochondria. We elaborate here on the observation
      that the GC skew is correlated with the distance from the replication origins.
      This effect has been explained as a consequence of the standard model of
      mitochondrial DNA replication, i.e. the strand displacement model. According to
      this model chemical damage accumulates proportional to the duration that DNA is
      exposed in single-stranded form during replication (Dssh) which depends on the
      relative position with respect to the replication origins. Based on this model we
      developed a computational method to infer the positions of both the heavy strand
      and the light strand origin from nucleotide skew data. In a comprehensive survey
      of deuterostome mitochondria we infer conserved replication origins for the vast
      majority of vertebrates and cephalochordates. Deviations from the consensus
      picture are presumably associated with genome rearrangements. 

PMID- 24911383
TI  - Heterologous expression from the human D-Loop in organello.
AB  - We report the expression of a linear reporter construct in isolated human
      mitochondria. The reporter construct contained the entire human D-Loop with
      adjacent tRNA (MTT) genes (mt.15956-647), the human ND1 gene with an in frame GFP
      gene and adjacent endogenous MTT genes and heterologous rat MTT genes. Natural
      competence of isolated human mitochondria of HepG2 cells was used to import
      reporter constructs. The import efficiency of various fluorescently labelled PCR
      generated import substrates in the range of 250bp up to 3.5kb was assessed by
      quantitative PCR and evaluated by confocal microscopy. Heterologous expression of
      the imported construct was confirmed at RNA level by a circular RNA (cRNA)-RT-PCR
      assay for the expression of tRNAs and by in organello [alpha-(32)P]-UTP labelling
      and subsequent hybridisation to reporter-specific sequences for monitoring mRNA
      expression. Heterologous expression of rat mitochondrial tRNA(Leu(UUR)) (rMT-TL1)
      was confirmed by co-/post-transcriptional trinucleotide (CCA) addition.
      Interestingly, the rat-specific MT-TL1 was correctly processed in isolated human
      mitochondria at the 3' end, but showed an aberrant 5' end processing. Correct 3'
      end processing of the heterologous expressed mitochondrial rat tRNA(Ser2) (MT
      TS2) was detected. These findings demonstrate the feasibility of genetic
      manipulation of human mitochondria, providing a tool for characterisation of cis
      acting elements of the human mitochondrial genome and for the study of human
      mitochondrial tRNA processing in organello. 

PMID- 24911384
TI  - Magnetic binary metal oxides affinity probe for highly selective enrichment of
      phosphopeptides.
AB  - In this work, for the first time, binary metal oxides ((Ti-Sn)O4) were integrated
      into one entity on an atomic scale on magnetic graphene as affinity probe for
      highly selective enrichment of phosphopeptides. The newly prepared
      Fe3O4/graphene/(Ti-Sn)O4 (magG/(Ti-Sn)O4) composites gathered the advantages of
      large specific surface area of graphene, superparamagnetism, and biocompatibility
      of iron oxide, and enhanced affinity properties of binary metal oxides. The
      phosphopeptide enrichment efficiency of the magG/(Ti-Sn)O4 composite was
      investigated, and the results indicated an ultralow detection limit (1 pg/MUL or
      4.0 * 10(-11) M) and an ultrahigh selectivity (weight ratio of beta-casein and
      BSA reached up to 1:1500). Compared with magnetic affinity probes with single
      metal oxide (magG/TiO2, magG/SnO2) or the simple physical mixture of magG/TiO2
      and magG/SnO2, the magG/(Ti-Sn)O4 composite possessed stronger specificity,
      higher selectivity and better efficiency; and more importantly, it possessed the
      ability to enrich both the mono- and multi- phosophorylated peptides,
      demonstrating the notable features of the novel binary metal oxides affinity
      probe in the specific and selective enrichment of phosphopeptides. Additionally,
      by utilizing the magG/(Ti-Sn)O4 composites, a total number of 349 phosphorylation
      sites on 170 phosphopeptides including 66 monophosphopeptides and 104
      multiphosphopeptides were captured and identified from mouse brain, indicating
      the great potential for their application in phosphoproteomics analysis in the
      future. 

PMID- 24911385
TI  - Engineered multifunctional nanomaterials for multimodal imaging of retinoblastoma
      cells in vitro.
AB  - Multifunctional nanoparticles are next generation materials that can be
      simultaneously used for imaging, diagnosis, and delivery of drugs. However,
      materials intended for cancer diagnosis need to be investigated for its cell
      uptake, toxicity, and effectiveness. In the current work, we have synthesized
      fluorescent iron oxide nanoparticles and evaluated its efficacy against
      retinoblastoma cell imaging. The iron oxide nanoparticles were synthesized and
      stabilized using oleic acid. Sulforhodamine B was adsorbed onto albumin over the
      oleic acid-capped iron oxide nanoparticles. Our results demonstrated good cell
      uptake in a time-dependent manner and nanoparticles were found to localize in the
      cytosol. Further, the nanoparticles exhibited excellent negative contrast in
      magnetic resonance imaging (MRI) experiments and with no cytoxicity (5-100 MUg/mL
      iron oxide nanoparticles) to both normal as well as cancer cells demonstrating
      its biocompatibility. Thus, this novel material integrates the ability to image
      tissues with high sensitivity by MRI and specifically visualize Y79
      retinoblastoma cells by fluorescence imaging with no toxicity. 

PMID- 24911386
TI  - HIV transactivator of transcription enhances methamphetamine-induced Parkinson's
      like behavior in the rats.
AB  - Abuse of methamphetamine (MA) increases the risk of infection of HIV-1, induces
      considerable neurotoxicity in several brain regions, and impairs the motor and
      cognitive function in individuals. HIV-1 transactivator of transcription (Tat)
      has also shown the potent capability to induce neuronal death and impaired brain
      function. The present study aims to study the synergistic effect of MA and Tat on
      cytokine synthesis in substantia nigra, striatal dopamine content, and behavioral
      performance in the rats. Although increased expression of cytokines (interleukin
      1beta and tumor necrosis factor-alpha) was observed in the substantia nigra in
      the rats receiving either MA or Tat alone, a combination of MA and Tat induced a
      larger and more sustained upregulation of cytokines. In the rats receiving either
      MA or Tat alone, significant loss in striatal dopamine content was found, which
      was further exacerbated in the rats receiving both MA and Tat. In the rats
      receiving either MA or Tat alone, significantly lower performance in the rotarod
      test and open-field test was observed, whereas the rats receiving both MA and Tat
      showed more sustained behavioral impairments. These results suggested that Tat
      protein synergized with MA to induce central neuroinflammation and impair the
      dopaminergic transmission, thus leading to sustained Parkinson's-like behavior.

PMID- 24911387
TI  - Evaluation of behavioral parameters and mortality in a model of temporal lobe
      epilepsy induced by intracerebroventricular pilocarpine administration.
AB  - The pilocarpine model of temporal lobe epilepsy (TLE) is a useful tool that is
      used to investigate the mechanisms underlying the generation and maintenance of
      seizures. Although this model has been modified significantly to reduce mortality
      and to promote the appearance of spontaneous recurrent seizures, to date, no
      detailed evaluation has been performed of the behavioral parameters and mortality
      in TLE induced by intracerebroventricular pilocarpine administration; therefore,
      this was the goal of the present study. A single dose of pilocarpine
      hydrochloride (2.4 mg in a total volume of 2 ul) was injected into the right
      lateral brain ventricle of rats; the convulsive behavior was rated using the
      Racine scale and the mortality was analyzed in these animals. We found that 30-90
      min after animals received intracerebroventricular pilocarpine injections, 73%
      developed status epilepticus (SE) with an activity score of 4/5 on the Racine
      scale. Moreover, these seizures were associated with the propagation of
      epileptiform activity to different hippocampal regions. Of the animals that
      developed SE, spontaneous recurrent seizures were observed in 32.5% at different
      times after SE induction. A 35% mortality rate was observed, which included
      animals that died during pilocarpine injection and after SE induction. On the
      basis of these findings, and given the observed latency between the insult (SE
      induction by pilocarpine injection) and the manifestation of spontaneous
      recurrent seizures, we propose that this model is a useful tool for basic
      biomedical research of SE and TLE.

PMID- 24911388
TI  - Morphological changes in glial fibrillary acidic protein immunopositive
      astrocytes in the hippocampus of dietary-induced obese mice.
AB  - Long-term consumption of a high-fat diet (HFD) has been shown to trigger both
      metabolic and cardiovascular diseases. In contrast, the effect of this type of
      dietary regime on the central nervous system, particularly outside the
      hypothalamus, has been investigated poorly. Astrocytes, the most abundant
      population of glial cells in the brain, are pivotal in regulating glutamatergic
      transmission as they are responsible for most of the glutamate uptake and
      metabolism. Mice on an HFD show deficits in learning and memory, together with
      neurochemical and electrophysiological changes compatible with the impairment in
      hippocampal glutamatergic activity. Because astrocyte function and morphology
      have been shown to be interdependent, we speculated whether HFD would trigger
      changes in astrocyte morphology. For this purpose, we have used a model of diet
      induced obesity in mice. We have analyzed astrocyte morphology and density by
      glial fibrillary acidic protein immunohistochemistry, as well as the expression
      of the glutamate transporters, GLT-1 (glutamate transporter type-1), and GLAST
      (astrocyte glutamate transporter), in the CA3 area of the hippocampus. We found
      that astrocytes from HFD mice showed longer and less abundant projections. These
      changes were accompanied by the upregulation of both GLT-1 and GLAST. Our data
      show that the functional impairment detected previously in HFD mice is
      concomitant with morphological changes within the hippocampus.

PMID- 24911389
TI  - Quetiapine reduces microglial number in the hippocampus of a transgenic mouse
      model of Alzheimer's disease.
AB  - Previous studies have suggested that the cerebral microglia activation was
      associated with Abeta plaques, whereas quetiapine, an atypical antipsychotic
      drug, decreased Abeta levels in Alzheimer's disease (AD) mice. The aim of the
      present study was to evaluate the effects of quetiapine on microglial activation
      in an amyloid precursor protein/presenilin-1 double transgenic mouse model of AD.
      Nontransgenic and transgenic mice were treated with quetiapine (0 or 5 mg/kg/day)
      in drinking water from the age of 2 months. After 10 months of continuous
      quetiapine administration, the mice were killed, and hippocampal microglial
      activation was measured by immunohistochemistry staining of CD11b-positive cells.
      The results showed that quetiapine significantly decreased the number of CD11b
      positive cells and beta-amyloid peptide levels in the hippocampus of transgenic
      mice. These suggest that quetiapine can attenuate microglia activation in an
      amyloid precursor protein/presenilin-1 transgenic mouse model of AD, and this may
      be related to quetiapine's beneficial effects in AD treatment.

PMID- 24911390
TI  - Sex-specific lateralization of event-related potential effects during mental
      rotation of polygons.
AB  - Mental rotation performance has been found to produce one of the largest sex
      differences in cognition. Many theories suggest that this effect should be
      accompanied by a sex difference in functional cerebral asymmetry, but empirical
      data are more than equivocal probably because of (a) the use of inappropriate
      stimuli and (b) insufficient power of most neurophysiological studies. Therefore,
      sex differences in mental rotation of polygons were investigated in 122 adults.
      Men outperformed women on mental rotation speed (as well as on response time and
      accuracy). On the basis of the electrophysiological brain correlates of mental
      rotation, we observed a bilateral brain activity for men, whereas women's brain
      activity was clearly lateralized toward the left hemisphere if and only if mental
      rotation was involved. Thus, sex differences in functional cerebral asymmetry can
      indeed be observed if appropriate stimuli are used in a sufficiently large
      sample.

PMID- 24911391
TI  - Brain activation patterns associated with the human comfortability of residential
      environments: 3.0-T functional MRI.
AB  - Residential environments are important in the daily lives of individuals,
      especially in terms of cognitive psychophysiology. This study compared the neural
      responses to two extreme residential environments: comfortable versus
      uncomfortable. Thirteen healthy individuals underwent a 3.0-T functional MRI
      while viewing images representing comfortable and uncomfortable residential
      environments. During exposure to the comfortable scenery, significant activation
      was observed in the calcarine gyrus selectively, whereas the uncomfortable
      scenery induced significant activation in the ventrolateral prefrontal cortex and
      anterior cingulate cortex, which are related to cognitive control, as well as in
      the medial prefrontal cortex, hippocampus, parahippocampal gyrus, amygdala, and
      insula, which are involved in the regulation and expression of emotion. Such
      differential brain activation patterns may reflect the neural networks mediating
      cognitive and emotional responses to residential environments. These findings
      would be helpful for understanding the neural mechanism associated with human
      comfortability for their residential environments. 

PMID- 24911392
TI  - User-only design to assess drug effectiveness in clinical practice: application
      to bisphosphonates and secondary prevention of fractures.
AB  - PURPOSE: Different strategies applicable to control for confounding by indication
      in observational studies were compared in a large population-based study
      regarding the effect of bisphosphonates (BPs) for secondary prevention of
      fractures. METHODS: The cohort was drawn from healthcare utilization databases of
      13 Italian territorial units. Patients aged 55 years or more who were
      hospitalized for fracture during 2003-2005 entered into the cohort. A nested case
      control design was used to compare BPs use in cohort members who did (cases) and
      who did not experience (controls) a new fracture until 2007 (outcome). Three
      designs were employed: conventional-matching (D1 ), propensity score-matching (D2
      ), and user-only (D3 ) designs. They differed for (i) cohort composition,
      restricted to patients who received BPs straight after cohort entry (D3 ); (ii)
      using propensity score for case-control matching (D2 ); and (iii) compared groups
      of BPs users versus no users (D1 and D2 ) and long-term versus short-term users
      (D3 ). RESULTS: Bisphosphonate users had odds ratios (95% confidence interval) of
      1.20 (1.01 to 1.44) and 0.95 (0.74 to 1.24) by applying D1 and D2 designs,
      respectively. Statistical evidence that long-term BPs use protects the outcome
      onset with respect to short-term use was observed for user-only design (D3 )
      being the corresponding odds ratio (95% confidence interval) 0.64 (0.44 to 0.93).
      CONCLUSIONS: User-only design yielded closer results to those seen in RCTs. This
      approach is one possible strategy to account for confounding by indication.

PMID- 24911393
TI  - The risks of not breastfeeding: new associations.

PMID- 24911394
TI  - ABM clinical protocol #4: Mastitis, revised March 2014.
AB  - A central goal of The Academy of Breastfeeding Medicine is the development of
      clinical protocols for managing common medical problems that may impact
      breastfeeding success. These protocols serve only as guidelines for the care of
      breastfeeding mothers and infants and do not delineate an exclusive course of
      treatment or serve as standards of medical care. Variations in treatment may be
      appropriate according to the needs of an individual patient. 

PMID- 24911395
TI  - Two new sesquiterpenoid glycosides from Nicotiana tabacum.
AB  - Two new sesquiterpenoid glycosides, nicotabalactonecoside (1) and
      nicotabadiolcoside (2), along with four known terpenoids (3-6) were isolated from
      the leaves of Nicotiana tabacum. The structures of compounds 1 and 2 were
      determined as dihydrodeacetylphytuberin-2-one 11-O-beta-D-glucopyranoside and 1,2
      dehydro-4-epieremophil-9-ene-11,12-diol 12-O-beta-D-glucopyranoside by extensive
      spectroscopic analyses (HR-ESI-MS, UV, IR, 1D, and 2D NMR) and chemical method.
      Compound 1 is an unusual phytuberin-type sesquiterpenoid with a 6/5/5 tricyclic
      system.

PMID- 24911396
TI  - Poly(vinyl alcohol) reinforced and toughened with poly(dopamine)-treated graphene
      oxide, and its use for humidity sensing.
AB  - Poly(dopamine)-treated graphene oxide/poly(vinyl alcohol) ("dG-O/PVA") composite
      films were made and characterized. G-O was modified with poly(dopamine) in
      aqueous solution and then chemically reduced to yield poly(dopamine)-treated
      reduced G-O. A combination of hydrogen bonding, strong adhesion of poly(dopamine)
      at the interface of PVA and G-O sheets, and reinforcement by G-O resulted in
      increases in tensile modulus, ultimate tensile strength, and strain-to-failure by
      39, 100, and 89%, respectively, at 0.5 wt % dG-O loading of the PVA. The dG-O
      serves as a moisture barrier for water-soluble PVA, and the dG-O/PVA composite
      films were shown to be effective humidity sensors over the relative humidity
      range 40-100%. 

PMID- 24911397
TI  - A Bayesian latent group analysis for detecting poor effort in a sample of
      cognitively impaired patients.
AB  - Using a Bayesian latent group analysis in a simulation design, we recently showed
      a high diagnostic accuracy when assessing effort in the context of malingered
      memory deficits. We here further evaluate our Bayesian model in a sample of
      cognitively impaired patients. The main analysis showed both high sensitivity and
      specificity, thus corroborating a high diagnostic accuracy of the model.
      Additional analysis showed variations on effort estimates after changes in
      malingering base rates. Variations affected sensitivity, but not specificity,
      which is in line with typical findings in malingering research. These data
      suggest that Bayesian analyses may complement and improve existing effort
      measures. 

PMID- 24911398
TI  - Mercury-induced dark-state instability and photobleaching alterations of the
      visual g-protein coupled receptor rhodopsin.
AB  - Mercuric compounds were previously shown to affect the visual phototransduction
      cascade, and this could result in vision impairment. We have analyzed the effect
      of mercuric chloride on the structure and stability of the dim light vision
      photoreceptor rhodopsin. For this purpose, we have used both native rhodopsin
      immunopurified from bovine retinas and a recombinant mutant rhodopsin carrying
      several Cys to Ser substitutions in order to investigate the potential binding
      site of mercury on the receptor. Our results show that mercuric chloride
      dramatically reduces the stability of dark-state rhodopsin and alters the
      molecular features of the photoactived conformation obtained upon illumination by
      eliciting the formation of an altered photointermediate. The thermal bleaching
      kinetics of native and mutant rhodopsin is markedly accelerated by mercury in a
      concentration-dependent manner, and its chromophore regeneration ability is
      severely reduced without significantly affecting its G-protein activation
      capacity. Furthermore, fluorescence spectroscopic measurements on the retinal
      release process, ensuing illumination, suggest that mercury impairs complete
      retinal release from the receptor binding pocket. Our results provide further
      support for the capacity of mercury as a hazardous metal ion with reported
      deleterious effect on vision and provide a molecular explanation for such an
      effect at the rhodopsin photoreceptor level. We suggest that mercury could alter
      vision by acting in a specific manner on the molecular components of the retinoid
      cycle, particularly by modifying the ability of the visual photoreceptor protein
      rhodopsin to be regenerated and to be normally photoactivated by light. 

PMID- 24911399
TI  - Membrane fouling by vesicles and prevention through ozonation.
AB  - Membrane fouling is a major challenge in water and wastewater treatment. Recent
      observations that ozone mitigates membrane fouling during filtration of secondary
      effluent prompted this study into the impact of preozonation on membrane fouling
      caused by biogenic colloids. The focus of this study was on liposomes, synthetic
      vesicles composed of (phospho)lipid bilayers, which are representative of the
      diverse cellular vesicles present in all biologically impacted waters. The
      overarching hypothesis was that these biologically produced, nonrigid or "soft"
      colloids (e.g., vesicles) present in wastewater give rise to unique fouling
      behavior that can be mitigated by preozonation. Using dead-end ultrafiltration
      (UF) and batch ozonation tests, the key findings of this study were (1) liposomes
      fouled UF membranes faster (4-13 times membrane cake resistance (RC) per mgC
      filtered) than polysaccharides, fatty acids, and NOM on a DOC-normalized basis;
      (2) based on the estimated carbon distribution of secondary effluent, liposome
      like biogenic nanomaterials could be responsible for 20-60% of fouling during UF;
      and (3) preozonation reduces liposomal fouling during UF, likely due to the
      disruption of the liposome structure through cleavage of the fatty acid tails at
      carbon-carbon double bonds. 

PMID- 24911400
TI  - Autoimmune aquaporin-4 myopathy in neuromyelitis optica spectrum.
AB  - IMPORTANCE: Documentation of muscle pathology compatible with targeting of
      sarcolemmal aquaporin-4 (AQP4) by complement-activating IgG implies involvement
      of organs beyond the central nervous system in neuromyelitis optica spectrum
      disorders. OBSERVATIONS: We report on a 51-year-old woman who had relapsing optic
      neuritis, transverse myelitis, AQP4-IgG seropositivity, and recurrent myalgias
      with hyperCKemia. A muscle biopsy revealed scattered myofibers with internal
      nuclei, atrophy, and regeneration but no necrosis. Mild inflammatory exudates, in
      endomysial and perivascular spaces, consisted of lymphocytes, histiocytes, and
      scattered eosinophils. The sarcolemma exhibited loss of AQP4 and deposition of
      IgG and complement activation products, characteristics not seen in control
      biopsy samples of healthy muscle and immune-mediated myopathies. CONCLUSIONS AND
      RELEVANCE: Recurrent hyperCKemia accompanying AQP4-IgG seropositivity reflects
      targeting of skeletal muscle AQP4 by pathogenic IgG. The entity of autoimmune
      AQP4 myopathy extends the neuromyelitis optica spectrum beyond the central
      nervous system.

PMID- 24911401
TI  - Are there standards of care for cardiac arrest existing in the workplace? Results
      from a worldwide survey.

PMID- 24911402
TI  - The availability, condition and employability of automated external
      defibrillators in large city centres in the Netherlands.
AB  - BACKGROUND: In the Netherlands there are, at the time of writing, no clear
      guidelines about the implementation of automated external defibrillators (AEDs).
      An observational study was conducted to investigate the current status of AEDs in
      city centres in the Netherlands looking specifically at the availability,
      condition and employability of the AEDs. METHODS AND RESULTS: The shopping areas
      in the old city centres of the six largest cities in the Netherlands were
      included in the study. After the AEDs had been identified, a questionnaire was
      used to determine the availability, condition and employability of the AED. In
      total 130 AEDs were found and 122 included in the study. The following results
      were found: 40% of the AEDs were not visible (range 21-64), 29% were not
      indicated with a sign (range 19-41), 7% had an empty battery (range 0-23), 16% of
      the defipads had expired (range 0-31) and in 98% of the AEDs a trained employee
      was present (range 96-100). After combining these results, 71% of the AEDs were
      available for use (range 61-93), 70% were in a good condition (range 46-82) and
      70% were employable (range 58-93). The results show a major variability between
      cities. CONCLUSION: Our study demonstrates that although national guidelines have
      not been implemented, a reasonable amount of AEDs can be found. However there is
      certainly room for improvement in the current availability, condition and
      employability of AEDs in city centres in the Netherlands.

PMID- 24911403
TI  - Creating a drowning chain of survival.
AB  - All nations would benefit from a simple, clear Drowning Chain of Survival. In
      high income nations this tool will refine prevention and the call for action. In
      low and middle income nations this tool is a guide for policy making, resource
      allocation and priority setting in drowning prevention. A best evidence approach
      was utilized to create a universal Drowning Chain of Survival. Education on how
      to prevent drowning and to how react when a drowning incident occurs has not
      always been guided by good levels of evidence, or high levels of specialized
      training in drowning process recognition and management. The Drowning Chain of
      Survival refers to a series of steps that when enacted, attempts to reduce
      mortality associated with drowning and attempted aquatic rescue. The term "chain
      of survival" has provided a useful metaphor for the elements of the emergency
      cardiac care system for sudden cardiac arrest, however interventions and patient
      management in drowning involves principles and actions that are specific to these
      situations. The result is a unique and universal Drowning Chain of Survival
      comprised of five links guiding the important life-saving steps for lay and
      professional rescuers. This may significantly improve chances of prevention,
      survival and recovery from drowning. The steps of the chain are: Prevent
      drowning, Recognize distress, Provide flotation, Remove from water, and Provide
      care as needed. 

PMID- 24911404
TI  - Racial differences in physical activity among breast cancer survivors:
      implications for breast cancer care.
AB  - BACKGROUND: Physical activity after breast cancer diagnosis is associated with
      improved survival. The current study examined levels of and changes in physical
      activity after breast cancer diagnosis, overall and by race. METHODS: Phase 3 of
      the Carolina Breast Cancer Study assessed both pre- and postdiagnosis physical
      activity levels in a cohort of 1735 women aged 20 years to 74 years who were
      diagnosed with invasive breast cancer between 2008 and 2011 in 44 counties of
      North Carolina. Logistic regression and analysis of variance were used to examine
      whether demographic, behavioral, and clinical characteristics were associated
      with activity levels. RESULTS: Only 35% of study participants met current
      physical activity guidelines after diagnosis with breast cancer. A decrease in
      activity after diagnosis was reported by 59% of patients, with the average study
      participant reducing their activity by 15 metabolic equivalent task (MET) hours
      (95% confidence interval [95% CI], 12 MET hours-19 MET hours). After adjustment
      for potential confounders, when compared with white women, African American women
      were less likely to meet national physical activity guidelines after diagnosis
      (odds ratio, 1.38; 95% CI, 1.01-1.88) and reported less weekly postdiagnosis
      physical activity (12 MET hours vs 14 MET hours; P = .13). In adjusted stratified
      analyses, receipt of treatment was found to be significantly associated with
      postdiagnosis activity in African American women (P < 0.01). CONCLUSIONS: Despite
      compelling evidence demonstrating the benefits of physical activity after a
      diagnosis of breast cancer, it is clear that more work needs to be done to
      promote physical activity in patients with breast cancer, especially among
      African American women.

PMID- 24911406
TI  - The influence of cholesterol on interactions and dynamics of ibuprofen in a lipid
      bilayer.
AB  - In this work, molecular dynamics (MD) simulations with atomistic details were
      performed to examine the influence of the cholesterol on the interactions and the
      partitioning of the hydrophobic drug ibuprofen in a fully hydrated 1,2
      dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer. Analysis of MD
      simulations indicated that ibuprofen molecules prefer to be located in the
      hydrophobic acyl chain region of DMPC/cholesterol bilayers. This distribution
      decreases the lateral motion of lipid molecules. The presence of ibuprofen
      molecules in the bilayers with 0 and 25mol% cholesterol increases the ordering of
      hydrocarbon tails of lipids whereas for the bilayers with 50mol% cholesterol,
      ibuprofen molecules perturb the flexible chains of DMPC lipids which leads to the
      reduction of the acyl chain order parameter. The potential of the mean force
      (PMF) method was used to calculate the free energy profile for the transferring
      of an ibuprofen molecule from the bulk water into the DMPC/cholesterol membranes.
      The PMF studies indicated that the presence of 50mol% cholesterol in the bilayers
      increases the free energy barrier and slows down the permeation of the ibuprofen
      drug across the DMPC bilayer. This can be due to the condensing and ordering
      effects of the cholesterol on the bilayer. 

PMID- 24911405
TI  - Nicotine accelerates diabetes-induced retinal changes.
AB  - PURPOSE: To investigate the effects of nicotine on retinal alterations in early
      stage diabetes in an established rodent model. MATERIALS AND METHODS: Sprague
      Dawley rats were examined using a combination of confocal scanning laser
      ophthalmoscopy and spectral domain optical coherence tomography to determine
      changes in retinal structure in response to nicotine exposure, diabetes and the
      combined effects of nicotine and diabetes. Diabetes was induced by a single
      injection of 65 mg/kg streptozotocin and nicotine injections were administered
      subcutaneously daily. Retinal thickness in the superior, inferior, nasal and
      temporal quadrants were determined based on the spectral domain optical coherence
      tomography (SD-OCT) volume scans (20 degrees  * 20 degrees ) centered on the
      optic disc. Segmentation of discrete retinal layers was performed on a subset of
      SD-OCT cross-sections to further examine changes in each treatment group.
      Survival of neurons within the ganglion cell layer (GCL) was assessed by confocal
      morphometric imaging. RESULTS: The control group did not experience any
      significant change throughout the study. The nicotine treatment group experienced
      an average decrease in total retinal thickness (TRT) of 9.4 um with the majority
      of the loss localized within the outer nuclear layer (ONL) as determined by
      segmentation analysis (p < 0.05). The diabetic group exhibited a trend toward
      decreased TRT while segmentation analysis of the diabetic retinopathy (DR) group
      revealed significant thinning within the ONL (p < 0.05). The combination of
      nicotine and diabetes revealed a significant increase of 8.9 um in the TRT (p <
      0.05) accompanied by a decrease in the number of GCL neurons. CONCLUSIONS: We
      demonstrated significant temporal changes in retinal morphology in response to
      nicotine exposure, diabetes and with the combined effects of nicotine and
      diabetes. These findings may have implications in determining treatment
      strategies for diabetic patients using products containing nicotine, such as
      cigarettes, smokeless tobacco, electronic cigarettes or smoking cessation
      products.

PMID- 24911408
TI  - Superior epigastric artery perforator flap: anatomy, clinical applications, and
      review of literature.
AB  - INTRODUCTION: To reduce donor site morbidity in anterior chest wall
      reconstruction, a flap based on perforators of the superior epigastric artery
      (SEA) was developed and successfully applied in a pedicled fashion for
      locoregional soft-tissue reconstruction. MATERIALS AND METHODS: We combined our
      anatomical and clinical experience with superior epigastric artery perforator
      (SEAP) flap with a PubMed search of the English language literature for articles
      published on "SEAP flap". Reference lists of the articles found were then checked
      for other related articles of interest. Articles were compared looking at flap
      indication, preoperative imaging, perforator morphology, SEA integument area,
      surgical approach, and outcome of the flaps. RESULTS: The four best perforators
      were most frequently encountered in an area 2 to 6 cm from the midline and 0 to
      10 cm below the xiphoid process. The territory of the SEAPs depends on the
      location of the perforator. Controversy exists in the current literature
      concerning preferable SEAP flap orientation. Although tip necrosis is the major
      complication, this can often be treated conservatively without affecting outcomes
      or can even be avoided by limiting flap length to the anterior axillary line and
      the zone below the midpoint between the xiphisternum and the umbilicus.
      CONCLUSION: The SEAP flap provides a useful approach for reconstruction of
      defects of the anterior chest, or of the abdominal wall. As a perforator or
      adipocutaneous flap, the flap is reliable and easy to raise, and spares donor
      site morbidity.

PMID- 24911407
TI  - Characterization of the Vibrio cholerae extracellular matrix: a top-down solid
      state NMR approach.
AB  - Bacterial biofilms are communities of bacterial cells surrounded by a self
      secreted extracellular matrix. Biofilm formation by Vibrio cholerae, the human
      pathogen responsible for cholera, contributes to its environmental survival and
      infectivity. Important genetic and molecular requirements have been identified
      for V. cholerae biofilm formation, yet a compositional accounting of these parts
      in the intact biofilm or extracellular matrix has not been described. As
      insoluble and non-crystalline assemblies, determinations of biofilm composition
      pose a challenge to conventional biochemical and biophysical analyses. The V.
      cholerae extracellular matrix composition is particularly complex with several
      proteins, complex polysaccharides, and other biomolecules having been identified
      as matrix parts. We developed a new top-down solid-state NMR approach to
      spectroscopically assign and quantify the carbon pools of the intact V. cholerae
      extracellular matrix using 13C CPMAS and 13C{(15N}, 15N{31P}, and 13C{31P}REDOR.
      General sugar, lipid, and amino acid pools were first profiled and then further
      annotated and quantified as specific carbon types, including carbonyls, amides,
      glycyl carbons, and anomerics. In addition, 15N profiling revealed a large amine
      pool relative to amide contributions, reflecting the prevalence of molecular
      modifications with free amine groups. Our top-down approach could be implemented
      immediately to examine the extracellular matrix from mutant strains that might
      alter polysaccharide production or lipid release beyond the cell surface; or to
      monitor changes that may accompany environmental variations and stressors such as
      altered nutrient composition, oxidative stress or antibiotics. More generally,
      our analysis has demonstrated that solid-state NMR is a valuable tool to
      characterize complex biofilm systems.

PMID- 24911409
TI  - Protecting your perforator markings.

PMID- 24911410
TI  - Morphomic analysis for preoperative donor site risk assessment in patients
      undergoing abdominal perforator flap breast reconstruction: a proof of concept
      study.
AB  - BACKGROUND: Morphomics are three-dimensional measurements of aspects of the human
      anatomy generated by computed tomographic (CT) imaging. The purpose of this study
      was to generate preliminary data on the efficacy of morphomics, as a potential
      risk stratification tool, in predicting abdominal donor site wound-healing
      complications in patients undergoing abdominal perforator flap breast
      reconstruction. Patients and METHODS: In total, 58 consecutive patients
      undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction
      were evaluated. Using preoperative CT scan data, we quantified patients' body
      area, visceral and subcutaneous fat, fascia area, and body depth between T12 and
      L4. Associations between morphomic measures and complication rates were examined
      using t-tests and logistic regression. RESULTS: Of the 58 patients, 11 (19%)
      patients developed a wound dehiscence and 47 (81%) patients healed their
      abdominal incision without complications. Patients with a dehiscence had a
      significantly higher body mass index (BMI) (34.32 vs. 29.26 kg/m(2), p = 0.014)
      than patients without a dehiscence. Multiple morphometric measures including
      higher visceral fat area (p = 0.003) were significant predictors of abdominal
      donor site wound dehiscence. BMI (odds ratio [OR], 1.16; 95% confidence interval
      [CI], 1.03-1.32; p = 0.017) and visceral fat area (OR, 1.24; 95% CI, 1.08-1.42; p
      = 0.002) were independently significant predictors for wound dehiscence in the
      entire sample. Only visceral fat area retained its predictive ability in patients
      with a BMI > 30 kg/m(2). CONCLUSIONS: Morphomic measurements correlate with the
      likelihood of developing postoperative donor site dehiscence after DIEP flap
      breast reconstruction. As a proof of concept study, this demonstrates that
      objective data obtained from CT scans may help in preoperatively assessing the
      risk for donor site wound healing complications in patients undergoing DIEP flap
      breast reconstruction.

PMID- 24911411
TI  - Microsurgical breast reconstruction in thin patients: the impact of low body mass
      indices.
AB  - BACKGROUND: The purpose of this investigation was to examine patients with low
      body mass index (BMI) regarding the feasibility to perform autologous breast
      reconstruction in such patients, as well as to determine optimal donor sites and
      evaluate outcomes accordingly. PATIENTS AND METHODS: All patients undergoing
      microsurgical breast reconstruction were divided into three cohorts based on BMI.
      Group 1 included patients with BMI greater than or equal to 22 kg/m(2) and was
      defined "low-normal BMI." Patients with BMI 22 to 25 kg/m(2) were placed in Group
      2, labeled as "high-normal BMI." Group 3, defined as "overweight," included
      patients with BMI greater than 25 kg/m(2), but less than 30 kg/m(2). Patients
      were then analyzed based on demographics, breast cancer history, intraoperative
      details, complications, and revisionary surgeries. F-tests, chi-square goodness
      of-fit tests, and Freeman-Halton extension of the Fisher exact tests were used
      for statistical analysis. RESULTS: During the study period, a total of 259
      reconstructions were performed. Group 1 included 30 patients (n = 49 flaps),
      Group 2 included 58 patients (n = 98 flaps), and Group 3 included 69 patients (n
      = 112 flaps). Patients undergoing nipple-areolar sparing mastectomy were more
      likely to be in Groups 1 (39% [n = 19]) and 2 (37% [n = 37]) as compared with
      Group 3 (14.2% [n = 16]) (p < 0.001) as compared with the overweight cohort.
      Patients with increasing BMI were more likely to undergo abdominally based free
      flaps as compared with alternative donor sites (Group 1 = 2.26, Group 2 = 7.9,
      Group 3 = 27 [p < 0.001]). CONCLUSIONS: Abdominally based free flaps are possible
      in the majority of patients, however alternative harvest sites have to be used
      more frequently in low BMI patients.

PMID- 24911412
TI  - Proteotoxicity is not the reason for the dependence of cancer cells on the major
      chaperone Hsp70.
AB  - Several years ago a hypothesis was proposed that the survival of cancer cells
      depend on elevated expression of molecular chaperones because these cells are
      prone to proteotoxic stress. A critical prediction of this hypothesis is that
      depletion of chaperones in cancer cells should lead to proteotoxicity. Here,
      using the major chaperone Hsp70 as example, we demonstrate that its depletion
      does not trigger proteotoxic stress, thus refuting the model. Accordingly, other
      functions of chaperones, e.g., their role in cell signaling, might define the
      requirements for chaperones in cancer cells, which is critical for rational
      targeting Hsp70 in cancer treatment. 

PMID- 24911413
TI  - Human genome variation and the concept of genotype networks.
AB  - Genotype networks are a concept used in systems biology to study sets of
      genotypes having the same phenotype, and the ability of these to bring forth
      novel phenotypes. In the past they have been applied to determine the genetic
      heterogeneity, and stability to mutations, of systems such as metabolic networks
      and RNA folds. Recently, they have been the base for reconciling the neutralist
      and selectionist views on evolution. Here, we adapted this concept to the study
      of population genetics data. Specifically, we applied genotype networks to the
      human 1000 genomes dataset, and analyzed networks composed of short haplotypes of
      Single Nucleotide Variants (SNV). The result is a scan of how properties related
      to genetic heterogeneity and stability to mutations are distributed along the
      human genome. We found that genes involved in acquired immunity, such as some HLA
      and MHC genes, tend to have the most heterogeneous and connected networks, and
      that coding regions tend to be more heterogeneous and stable to mutations than
      non-coding regions. We also found, using coalescent simulations, that regions
      under selection have more extended and connected networks. The application of the
      concept of genotype networks can provide a new opportunity to understand the
      evolutionary processes that shaped our genome. Learning how the genotype space of
      each region of our genome has been explored during the evolutionary history of
      the human species can lead to a better understanding on how selective pressures
      and neutral factors have shaped genetic diversity within populations and among
      individuals. Combined with the availability of larger datasets of sequencing
      data, genotype networks represent a new approach to the study of human genetic
      diversity that looks to the whole genome, and goes beyond the classical division
      between selection and neutrality methods. 

PMID- 24911414
TI  - Allele-specific methylation occurs at genetic variants associated with complex
      disease.
AB  - We hypothesize that the phenomenon of allele-specific methylation (ASM) may
      underlie the phenotypic effects of multiple variants identified by Genome-Wide
      Association studies (GWAS). We evaluate ASM in a human population and document
      its genome-wide patterns in an initial screen at up to 380,678 sites within the
      genome, or up to 5% of the total genomic CpGs. We show that while substantial
      inter-individual variation exists, 5% of assessed sites show evidence of ASM in
      at least six samples; the majority of these events (81%) are under genetic
      influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral
      blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with
      variants linked to complex disease. Finally, focusing on autoimmune phenotypes,
      we extend this initial screen to confirm the association of cis-regulated ASM
      with multiple complex disease-associated variants in an independent population
      using next-generation bisulfite sequencing. These four variants are implicated in
      complex phenotypes such as ulcerative colitis and AIDS progression disease
      (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and
      early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our
      results suggest cis-regulated ASM may provide a mechanistic link between the non
      coding genetic changes and phenotypic variation observed in these diseases and
      further suggests a route to integrating DNA methylation status with GWAS results.

PMID- 24911415
TI  - Most human proteins made in both nucleus and cytoplasm turn over within minutes.
AB  - In bacteria, protein synthesis can be coupled to transcription, but in eukaryotes
      it is believed to occur solely in the cytoplasm. Using pulses as short as 5 s, we
      find that three analogues--L-azidohomoalanine, puromycin (detected after
      attaching fluors using 'click' chemistry or immuno-labeling), and amino acids
      tagged with 'heavy' 15N and 13C (detected using secondary ion mass spectrometry)-
      are incorporated into the nucleus and cytoplasm in a process sensitive to
      translational inhibitors. The nuclear incorporation represents a significant
      fraction of the total, and labels in both compartments have half-lives of less
      than a minute; results are consistent with most newly-made peptides being
      destroyed soon after they are made. As nascent RNA bearing a premature
      termination codon (detected by fluorescence in situ hybridization) is also
      eliminated by a mechanism sensitive to a translational inhibitor, the nuclear
      turnover of peptides is probably a by-product of proof-reading the RNA for stop
      codons (a process known as nonsense-mediated decay). We speculate that the
      apparently-wasteful turnover of this previously-hidden ('dark-matter') world of
      peptide is involved in regulating protein production.

PMID- 24911416
TI  - Co-authorship and bibliographic coupling network effects on citations.
AB  - This paper analyzes the effects of the co-authorship and bibliographic coupling
      networks on the citations received by scientific articles. It expands prior
      research that limited its focus on the position of co-authors and incorporates
      the effects of the use of knowledge sources within articles: references. By
      creating a network on the basis of shared references, we propose a way to
      understand whether an article bridges among extant strands of literature and
      infer the size of its research community and its embeddedness. Thus, we map onto
      the article--our unit of analysis--the metrics of authors' position in the co
      authorship network and of the use of knowledge on which the scientific article is
      grounded. Specifically, we adopt centrality measures--degree, betweenneess, and
      closeness centrality--in the co-authorship network and degree, betweenness
      centrality and clustering coefficient in the bibliographic coupling and show
      their influence on the citations received in first two years after the year of
      publication. Findings show that authors' degree positively impacts citations.
      Also closeness centrality has a positive effect manifested only when the giant
      component is relevant. Author's betweenness centrality has instead a negative
      effect that persists until the giant component--largest component of the network
      in which all nodes can be linked by a path--is relevant. Moreover, articles that
      draw on fragmented strands of literature tend to be cited more, whereas the size
      of the scientific research community and the embeddedness of the article in a
      cohesive cluster of literature have no effect.

PMID- 24911417
TI  - Patterns of compensatory behaviors and disordered eating in college students.
AB  - Abstract. OBJECTIVE: The current study investigated rates of endorsement of
      eating-related compensatory behaviors within a college sample. PARTICIPANTS: This
      sample included male and female students (N = 1,158). METHODS: PARTICIPANTS
      completed the Eating Disorder Examination Questionnaire (EDE-Q). The study
      defined 3 groups of students: those who did not endorse purging behaviors, those
      who endorsed only exercise, and those who endorsed laxative use or vomiting.
      Rates of related eating disorder risk variables were compared across the 3
      groups. RESULTS: Almost half of college students reported utilizing exercise as a
      compensatory strategy over the past 28 days. Those reporting compensatory
      exercise did not differ from other community and college samples on EDE-Q
      subscales. CONCLUSIONS: Findings suggest that college students report significant
      rates of compensatory exercise, and those who report exercise as their only
      compensatory behavior also report relatively low levels of eating disorder risk.

PMID- 24911418
TI  - Circulating microRNA expression profiles in ovarian cancer.
AB  - MicroRNA (miRNA) is an abundant class of small non-coding RNAs that act as gene
      regulators. Recent studies have suggested that miRNA deregulation is associated
      with the initiation and progression of human cancer. However, information about
      ovarian cancer-related miRNA is mostly limited to tissue miRNA. The aim of this
      study was to find specific profiles of plasma-derived miRNAs of ovarian cancer.
      In this present study, the expression profiles of 740 miRNAs in plasma from 18
      patients and 24 healthy women subjects were evaluated using microfluidic based
      multiplex qRT-PCR. Our results demonstrated that expression levels of eight
      miRNAs were significantly upregulated in patients with ovarian cancer when
      compared with a control group (p < 0.05). Expression levels of four miRNAs were
      found significantly downregulated in patients with ovarian cancer (p < 0.05). In
      addition, 10 miRNAs were expressed only in the ovarian cancer group and miR-138
      5p of these miRNAs is ovarian specific. In conclusion, our study suggests that
      detecting these ovarian cancer specific miRNAs in plasma might serve as novel non
      invasive biomarkers for ovarian cancer.

PMID- 24911419
TI  - Complete NMR assignment of cyclic octapeptide CTAP.

PMID- 24911421
TI  - Telephone-based problem-solving intervention for family caregivers of stroke
      survivors: a randomized controlled trial.
AB  - OBJECTIVE: Intervention trials for stroke caregivers after the early poststroke
      period are lacking. To address this gap, we examined the effectiveness of a
      problem-solving intervention (PSI) for stroke caregivers who provided care for at
      least 6 months and who experienced significant strain in their role. METHOD: One
      hundred twenty-two family caregivers (age = 66.2 years, 77.9% female) were
      randomly allocated to a PSI or control group. The PSI was composed of 2 home
      visits and 18 telephone calls delivered over a 3-month intensive intervention and
      a 9-month maintenance period. PSI and control groups received monthly information
      letters in addition to usual care. Primary caregiver outcomes were depressive
      symptoms (measure: Center for Epidemiologic Studies-Depression Scale) and sense
      of competence (measure: Sense of Competence Questionnaire). RESULTS: In
      covariance analyses, caregivers of the PSI group showed significantly lower
      levels of depressive symptoms after 3 months (p < .01, d = -.48) and after 12
      months (p < .05, d = -.37), but no better sense of competence compared with the
      control group. Latent growth curve analyses revealed positive significant (p <
      .05) linear and quadratic effects of PSI on both primary outcomes. No effects,
      however, were found on caregiver social-problem-solving abilities. CONCLUSIONS:
      Although beneficial effects were observed among caregivers in the PSI group, the
      lack of effects on problem-solving abilities implies other characteristics of the
      intervention might account for these benefits. The relative intensity and
      therapeutic contact during the first 3 months of the intervention may be
      particularly helpful to caregivers of stroke survivors.

PMID- 24911420
TI  - Randomized clinical trial of cognitive behavioral social skills training for
      schizophrenia: improvement in functioning and experiential negative symptoms.
AB  - OBJECTIVE: Identifying treatments to improve functioning and reduce negative
      symptoms in consumers with schizophrenia is of high public health significance.
      METHOD: In this randomized clinical trial, participants with schizophrenia or
      schizoaffective disorder (N = 149) were randomly assigned to cognitive behavioral
      social skills training (CBSST) or an active goal-focused supportive contact
      (GFSC) control condition. CBSST combined cognitive behavior therapy with social
      skills training and problem-solving training to improve functioning and negative
      symptoms. GFSC was weekly supportive group therapy focused on setting and
      achieving functioning goals. Blind raters assessed functioning (primary outcome:
      Independent Living Skills Survey [ILSS]), CBSST skill knowledge, positive and
      negative symptoms, depression, and defeatist performance attitudes. RESULTS: In
      mixed-effects regression models in intent-to-treat analyses, CBSST skill
      knowledge, functioning, amotivation/asociality negative symptoms, and defeatist
      performance attitudes improved significantly more in CBSST relative to GFSC. In
      both treatment groups, comparable improvements were also found for positive
      symptoms and a performance-based measure of social competence. CONCLUSIONS: The
      results suggest CBSST is an effective treatment to improve functioning and
      experiential negative symptoms in consumers with schizophrenia, and both CBSST
      and supportive group therapy actively focused on setting and achieving
      functioning goals can improve social competence and reduce positive symptoms.

PMID- 24911422
TI  - Cognitive processing therapy for veterans with posttraumatic stress disorder: a
      comparison between outpatient and residential treatment.
AB  - OBJECTIVE: Across the Veterans Affairs (VA) Healthcare System, outpatient and
      residential posttraumatic stress disorder (PTSD) treatment programs are available
      to veterans of all ages and both genders; however, no research to date has
      compared these treatment options. This study compared veterans who received
      outpatient (n = 514) to those who received residential treatment (n = 478) within
      a VA specialty clinic on demographic and pretreatment symptom variables. Further,
      the study examined pre- to posttreatment symptom trajectories across the
      treatment programs. METHOD: All 992 veterans met diagnostic criteria for PTSD and
      attended at least 1 session of cognitive processing therapy (CPT) in either the
      outpatient or residential program. Bivariate analyses were utilized to
      investigate differences between samples on demographic variables and severity of
      pretreatment symptoms. Multilevel modeling (MLM) was used to investigate the
      change in symptomatology between the 2 samples from pre- to posttreatment.
      RESULTS: Analyses indicated that the samples differed on all demographic and
      pretreatment symptom variables, with residential patients reporting higher scores
      on all assessment measures. MLM results demonstrated that symptom scores improved
      for all veterans across time, with outpatients consistently reporting fewer
      symptoms at both time points. The time by program interaction was significant for
      PTSD-related symptom trajectories, but not for the depression-related symptom
      trajectory. CONCLUSION: This is the 1st study to compare pretreatment
      characteristics and treatment outcome between veterans receiving outpatient and
      residential PTSD treatment. Findings may help clinicians select appropriate care
      for their patients by identifying relevant pretreatment characteristics and
      generally informing expectations of treatment outcome.

PMID- 24911423
TI  - Telephone-delivered cognitive behavioral therapy for high anxiety sensitivity: a
      randomized controlled trial.
AB  - OBJECTIVE: High anxiety sensitivity (AS) is associated with the development and
      maintenance of anxiety and depressive symptoms and is theorized to be a mediator
      of treatment outcomes for anxiety and depression. The present study tested the
      efficacy of a telephone-delivered cognitive behavioral therapy (CBT) intervention
      in reducing high AS and its associated anxiety and depressive symptoms. METHOD:
      Treatment-seeking participants with high AS were recruited from the community (N
      = 80; M age = 36 years; 79% women; 76% Caucasian) and were randomly assigned to
      an 8-week telephone-delivered CBT program or a waiting list control. Participants
      completed anxiety and depression symptom and diagnostic measures at pre- and
      posttreatment, after a subsequent 4 weeks of continued interoceptive exposure,
      and 8 weeks later. RESULTS: Multilevel modeling showed the treatment was
      successful in reducing AS, as well as panic, social phobia, posttraumatic stress
      symptoms, and number of Diagnostic and Statistical Manual of Mental Disorders
      (4th ed.; American Psychiatric Association, 1994) diagnoses per participant when
      compared to a waiting list control. These gains were maintained at follow-up.
      Generalized anxiety and depressive symptoms, however, did not improve as a result
      of treatment. Mediated moderation analyses suggested that treatment-related
      changes in AS may mediate anxiety symptom changes. CONCLUSION: RESULTS of the
      present study provide promising evidence for this transdiagnostic treatment
      approach. Reductions in anxiety symptoms across diagnostic categories stemming
      from this AS-targeted intervention may have implications for helping a broad
      array of clients with various anxiety disorders that share AS as a common risk or
      maintenance factor.

PMID- 24911424
TI  - Chemoselective reduction of alpha-keto amides using nickel catalysts.
AB  - Ni-catalysts are used for the first time to synthesize highly important alpha
      hydroxy amides and beta-amino alcohols from alpha-keto amides by chemoselective
      and complete reduction using hydrosilanes. Chemoselective complete reduction of
      alpha-keto amides in the presence of a simple amide group is a key benefit of
      these Ni-catalysts. 

PMID- 24911426
TI  - Short-term treatment experience with teriparatide in pregnancy- and lactation
      associated osteoporosis.

PMID- 24911425
TI  - Ambient temperature and dietary supplementation interact to shape mosquito vector
      competence for malaria.
AB  - The extent to which environmental factors influence the ability of Anopheles
      mosquitoes to transmit malaria parasites remains poorly explored. Environmental
      variation, such as change in ambient temperature, will not necessarily influence
      the rates of host and parasite processes equivalently, potentially resulting in
      complex effects on infection outcomes. As proof of principle, we used Anopheles
      stephensi and the rodent malaria parasite, Plasmodium yoelii, to examine the
      effects of a range of constant temperatures on one aspect of host defense
      (detected as alterations in expression of nitric oxide synthase gene - NOS) to
      parasite infection. We experimentally boosted mosquito midgut immunity to
      infection through dietary supplementation with the essential amino acid l
      Arginine (l-Arg), which increases midgut nitric oxide (NO) levels by infection
      induced NOS catalysis in A. stephensi. At intermediate temperatures,
      supplementation reduced oocyst prevalence, oocyst intensity, and sporozoite
      prevalence suggesting that the outcome of parasite infection was potentially
      dependent upon the rate of NOS-mediated midgut immunity. At low and high
      temperature extremes, however, infection was severely constrained irrespective of
      supplementation. The effects of l-Arg appeared to be mediated by NO-dependent
      negative feedback on NOS expression, as evidenced by depressed NOS expression in
      l-Arg treated groups at temperatures where supplementation decreased parasite
      infection. These results suggest the need to consider the direct (e.g. effects of
      mosquito body temperature on parasite physiology) and indirect effects (e.g.
      mediated through changes in mosquito physiology/immunity) of environmental
      factors on mosquito-malaria interactions in order to understand natural variation
      in vector competence. 

PMID- 24911427
TI  - The effect of rate of weight reduction on serum myostatin and follistatin
      concentrations in competitive wrestlers.
AB  - PURPOSE: To evaluate anthropometric measures and serum markers of myostatin
      pathway activity after different weight-reduction protocols in wrestlers.
      METHODS: Subjects were randomly assigned to a gradual-weight-reduction (GWR) or
      rapid-weight-reduction (RWR) group. Food logs were collected for the duration of
      the study. Anthropometric measurements and serum samples were collected after an
      8-h fast at baseline and after the weight-reduction intervention. Subjects
      reduced body mass by 4%. The GWR group restricted calories over 12 d, while the
      RWR group restricted calories over 2 d. A series of 2*5 repeated-measures (RM)
      ANOVAs was conducted to examine differences in nutrient consumption, while
      separate 2*2 RM ANOVAs were conducted to examine differences in anthropometric
      measures and serum markers. When applicable, Tukey post hoc comparisons were
      conducted. Significance for all tests was set at P<.05. RESULTS: There were no
      between-groups differences for any anthropometric measure (P>.05). Subjects in
      both groups experienced a significant reduction in body mass, fat mass, lean
      mass, and percent body fat (P<.05). There were no between-groups differences in
      serum markers of myostatin-pathway activity (P>.05), but subjects in the RWR
      condition experienced a significant increase in serum myostatin (P<.01), a
      decrease in follistatin (P<.01), and an increase in myostatin-to-follistatin
      ratio (P<.001). CONCLUSION: Although there were no between-groups differences for
      any outcome variables, the serum myostatin-to-follistatin ratio was significantly
      increased in the RWR group, possibly signaling the early stages of skeletal
      muscle catabolism.

PMID- 24911428
TI  - Enriching tortoises: assessing color preference.
AB  - Environmental enrichment is a principle that is used to enhance the quality of
      care for nonhuman animals in captivity. To achieve this, it is necessary to
      understand the animal's needs. This study focused on color preference to provide
      food stimuli as a source of environmental enrichment for the tortoise,
      Chelonoidis denticulata. During this study, the stimuli green-, blue-, yellow-,
      and red-colored bananas and plaster blocks were randomly offered to the
      tortoises. Analysis of the data showed that the tortoises had a preference for
      the stimuli dyed with colors red and yellow over the other presented colors. It
      was possible to conclude that presenting food in different colors stimulated the
      animals to evaluate their environment and make choices in relation to their color
      preference. Thus, this experiment introduced an element of choice into their
      lives, beyond identifying color food preferences for the tortoises. The element
      of choice is known to be important to animal welfare. 

PMID- 24911429
TI  - Functional analysis of aggression in a black-and-white ruffed lemur (Varecia
      variegata variegata).
AB  - A functional analysis was conducted to assess the antecedent and reinforcing
      conditions underlying aggressive behavior in a female lemur in captivity. Results
      showed that her aggression was primarily the result of human attention. A
      replacement behavior-training program was introduced, and the lemur's aggression
      was successfully eliminated. These results demonstrate the utility of using
      functional assessment and analyses in zoos with captive wild nonhuman animals. 

PMID- 24911430
TI  - TLR cross-talk confers specificity to innate immunity.
AB  - Cross-talk within the innate immune pathways is highly complex and contains many
      unknowns. Here, we discuss the different combinations of PAMPs, together with the
      sequence, order, and dosage of consecutive PAMP challenges, which determine the
      nature of the immune response by macrophages. The engagement of different Toll
      like receptor (TLR) ligands leads to quantitatively and qualitatively unique
      cytokine production, showing that TLR pathway crosstalk enables the innate immune
      system to orchestrate immediate local and global responses. It is likely that
      multiple pathways are involved in the regulation of cytokine synergy, including
      many that have yet to be discovered. 

PMID- 24911432
TI  - Twice- or once-daily dosing of novel oral anticoagulants for stroke prevention: a
      fixed-effects meta-analysis with predefined heterogeneity quality criteria.
AB  - BACKGROUND: A number of novel oral anticoagulants (direct thrombin inhibitors or
      factor Xa inhibitors) are in clinical use for various indications. The dosing
      regimens differ between twice-daily and once-daily dosing for the prevention of
      stroke in patients with atrial fibrillation. With the availability of the results
      from four phase 3 studies (>70,000 patients), we explored whether twice-daily or
      once-daily dosing provides better risk-benefit balance among novel oral
      anticoagulants. METHODS: We conducted a strict, stepwise, fixed-effects meta
      analysis with predefined heterogeneity quality criteria to generate the most
      appropriate common estimates for twice-daily (BID) or once-daily (QD) dosing
      regimens. An indirect comparison of these dosing regimens with fixed-effects meta
      analysis common estimates (where available), or individual compound results, was
      done respectively. RESULTS: Comparing indirectly BID vs QD dosing regimens
      resulted in hazard ratios (HR [95% confidence interval]) for stroke and systemic
      embolism of 0.75 (0.58-0.96) for dabigatran 150 mg BID, and 0.91 (0.73-1.13) for
      apixaban BID vs the QD dosing regimen. For ischemic stroke, the HR of BID vs QD
      was 0.85 (0.69-1.05). For intracranial hemorrhage, BID vs rivaroxaban QD was 0.57
      (0.37-0.88) and, vs edoxaban QD, 0.81 (0.54-1.22). Due to heterogeneity, common
      estimates for major bleeding QD or BID were not justified, therefore indirect
      comparison of regimens were not possible. All non-vitamin K antagonist oral
      anticoagulants reduced all-cause mortality vs warfarin with a HR of 0.90 (0.86
      0.96) without differences between regimen. CONCLUSIONS: Based on the available
      phase 3 study evidence, the twice-daily dosing regimen of non-vitamin K
      antagonist oral anticoagulants appears to offer a more balanced risk-benefit
      profile with respect to stroke prevention and intracranial hemorrhage.

PMID- 24911431
TI  - Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation
      of Autoimmune Disease.
AB  - The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the
      immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and
      consequent regulation of immune function is an exciting area of research with
      potential implications in the prevention and treatment of inflammatory and
      autoimmune diseases. Despite significant advances in understanding the mechanisms
      through which cannabinoids regulate immune functions, not much is known about the
      role of endocannabinoids in the pathogenesis or prevention of autoimmune
      diseases. Inasmuch as CB2 expression on immune cells and its role has been widely
      reported, the importance of CB1 in immunological disorders has often been
      overlooked especially because it is not highly expressed on naive immune cells.
      Therefore, the current review aims at delineating the effect of endocannabinoids
      on CB1 receptors in T cell driven autoimmune diseases. This review will also
      highlight some autoimmune diseases in which there is evidence indicating a role
      for endocannabinoids in the regulation of autoimmune pathogenesis. Overall, based
      on the evidence presented using the endocannabinoids, specifically AEA, we
      propose that the peripheral CB1 receptor is involved in the regulation and
      amelioration of inflammation associated with autoimmune diseases. 

PMID- 24911433
TI  - Refining a personalized mHealth intervention to promote medication adherence
      among HIV+ methamphetamine users.
AB  - Mobile health (mHealth) interventions to promote antiretroviral therapy (ART)
      adherence have shown promise; however, among persons living with HIV who abuse
      methamphetamine (MA), effective tailoring of content to match the expressed needs
      of this patient population may be necessary. This study aimed (1) to understand
      patient perspectives of barriers and facilitators of ART adherence among people
      with HIV who use MA, and (2) to obtain feedback on the thematic content of an
      mHealth intervention in order to tailor the intervention to this subgroup. Two
      separate focus groups, each with 10 HIV+/MA+ individuals, were conducted.
      Transcribed audio recordings were qualitatively analyzed to identify emergent
      themes. Inter-rater reliability of themes was high (mean Kappa = .97). Adherence
      barriers included MA use, misguided beliefs about ART adherence, memory and
      planning difficulties, social barriers and perceived stigma, and mental heath
      issues. Facilitators of effective ART adherence were cognitive compensatory
      strategies, promotion of well-being, health-care supports, adherence education,
      and social support. Additionally, the focus groups generated content for reminder
      text messages to be used in the medication adherence intervention. This
      qualitative study demonstrates the feasibility of using focus groups to derive
      patient-centered intervention content to address the health challenge at hand in
      targeted populations. 

PMID- 24911434
TI  - Long-term recovery from hippocampal-related behavioral and biochemical
      abnormalities induced by noise exposure during brain development. Evaluation of
      auditory pathway integrity.
AB  - Sound is an important part of man's contact with the environment and has served
      as critical means for survival throughout his evolution. As a result of exposure
      to noise, physiological functions such as those involving structures of the
      auditory and non-auditory systems might be damaged. We have previously reported
      that noise-exposed developing rats elicited hippocampal-related histological,
      biochemical and behavioral changes. However, no data about the time lapse of
      these changes were reported. Moreover, measurements of auditory pathway function
      were not performed in exposed animals. Therefore, with the present work, we aim
      to test the onset and the persistence of the different extra-auditory
      abnormalities observed in noise-exposed rats and to evaluate auditory pathway
      integrity. Male Wistar rats of 15 days were exposed to moderate noise levels (95
      97 dB SPL, 2 h a day) during one day (acute noise exposure, ANE) or during 15
      days (sub-acute noise exposure, SANE). Hippocampal biochemical determinations as
      well as short (ST) and long term (LT) behavioral assessments were performed. In
      addition, histological and functional evaluations of the auditory pathway were
      carried out in exposed animals. Our results show that hippocampal-related
      behavioral and biochemical changes (impairments in habituation, recognition and
      associative memories as well as distortion of anxiety-related behavior, decreases
      in reactive oxygen species (ROS) levels and increases in antioxidant enzymes
      activities) induced by noise exposure were almost completely restored by PND 90.
      In addition, auditory evaluation shows that increased cochlear thresholds
      observed in exposed rats were re-established at PND 90, although with a
      remarkable supra-threshold amplitude reduction. These data suggest that noise
      induced hippocampal and auditory-related alterations are mostly transient and
      that the effects of noise on the hippocampus might be, at least in part, mediated
      by the damage on the auditory pathway. However, we cannot exclude that a
      different mechanism might be responsible for the observed hippocampal-related
      changes.

PMID- 24911435
TI  - Acute movement disorders associated with the use of second-generation
      antipsychotics in borderline personality disorder: a meta-analysis.

PMID- 24911436
TI  - Statistics commentary series: commentary #3--last observation carried forward.

PMID- 24911437
TI  - Augmentation of clozapine with agomelatine in partial-responder schizophrenia: a
      16-week, open-label, uncontrolled pilot study.
AB  - The present 16-week open-label uncontrolled trial was aimed to explore the
      efficacy of adjunctive agomelatine on clinical symptoms and cognitive functioning
      in 20 schizophrenia patients showing partial response (Brief Psychiatric Rating
      Scale, mean [SD] baseline total score = 37.5 [6.6]) to clozapine monotherapy at
      the highest tolerated dosage. The results obtained evidenced that agomelatine at
      a dosage of 50 mg/d was associated with score reduction in all Positive and
      Negative Syndrome Scale domains (positive, P = 0.011 and Cohen d = 0.7; negative,
      P < 0.0001 and Cohen d = 1.1; psychopathology, P = 0.001 and Cohen d = 0.9) and
      total score (P = 0.001, Cohen d = 1.2), depressive (Calgary Depression Scale for
      Schizophrenia, P = 0.013 and Cohen d = 0.6), and overall clinical symptoms (Brief
      Psychiatric Rating Scale, P = 0.001 and Cohen d = 0.6 ); moreover, improved
      performances on Stroop task (P = 0.006, Cohen d = 0.7) and Wisconsin Card Sorting
      Test "perseverative errors" (P = 0.033, Cohen d = 0.3) were observed. The
      favorable effect of agomelatine on clinical and cognitive symptoms was
      encouraging, and more research is needed to better identify subgroups of patients
      who are partially responsive to clozapine monotherapy in which agomelatine
      augmentation may be of benefit. 

PMID- 24911440
TI  - Prolactin deficiency by aripiprazole.

PMID- 24911438
TI  - Discontinuation of antidepressants during attempts to conceive: a pilot trial of
      cognitive behavioral therapy for the prevention of recurrent depression.
AB  - BACKGROUND: Many women discontinue antidepressants (ADs) when trying to conceive,
      although risk of depressive relapse is high. We examined the feasibility and
      potential clinical effect of cognitive behavioral therapy for the prevention of
      recurrence (CBT-PR) for women with a history of recurrent major depressive
      disorder (MDD) who planned to discontinue maintenance AD treatment for pregnancy.
      METHODS: This was an open preliminary study of CBT-PR in women (N = 12) planning
      or early in pregnancy with remitted MDD on maintenance ADs with a plan to
      discontinue ADs for pregnancy. Participants received 12 sessions of CBT-PR during
      the acute phase and optional monthly booster sessions during follow-up.
      Participants were assessed monthly during the acute phase and then twice
      additionally during follow-up by an independent rater using mood scales
      (depression module of the Mini-International Neuropsychiatric Interview and
      Montgomery-Asberg Depression Rating Scale); pregnancy status was also assessed.
      RESULTS: Over the 24 weeks of the trial, 75% (n = 9) of participants did not
      restart ADs and did not relapse to depression. Of the 3 who reintroduced AD, 2
      experienced a depressive relapse, whereas one did not meet full criteria for MDD.
      Adherence to the intervention was very good with all participants completing all
      therapy sessions and assessments. CONCLUSIONS: Cognitive behavioral therapy for
      the prevention of recurrence seems feasible and may provide protection for women
      with recurrent depression on ADs who discontinue their medication while trying to
      conceive. The extent to which euthymia is sustainable with CBT-PR requires
      further study; the results of which may broaden treatment choices for women in
      anticipation of and during pregnancy.

PMID- 24911439
TI  - Lack of effect of risperidone or olanzapine dose reduction on metabolic
      parameters, prolactin, and corrected QT interval in stable patients with
      schizophrenia.

PMID- 24911441
TI  - Antibiotic-associated psychosis during treatment of urinary tract infections: a
      systematic review.
AB  - There have been a number of case reports of antibiotic-associated psychosis in
      the literature that have not been systematically reviewed. Urinary tract
      infections (UTIs) are among the most common bacterial infections and have also
      been associated with acute psychosis. We performed a systematic review of cases
      of antibiotic-associated acute psychosis during treatment of a UTI and evaluated
      the strength of the association for each case. We identified reports by searching
      PubMed, PsychINFO, and Web of Knowledge, and the reference lists of identified
      reports. We systematically evaluated the quality of the causal relationship
      between antibiotic treatment of UTI and psychosis. Fourteen articles (describing
      15 different cases) met the inclusion criteria. The primary findings were as
      follows: (1) a majority (60%) of reported cases were "highly suggestive" of a
      potential causal relationship between antibiotic treatment and psychosis,
      including 3 cases with a recurrence of psychosis after rechallenge with the same
      antibiotic; (2) 3 different classes of antibiotics were implicated in this
      association, including fluoroquinolones, penicillins, and trimethoprim
      sulfamethoxazole; (3) for most of the reported cases, both the onset and
      resolution of psychosis occurred within 1 week of initiation and discontinuation
      of the antibiotic, respectively; (4) approximately half of the cases did not
      require treatment with antipsychotics; and (5) affected men were significantly
      more likely to have a psychiatric history. Our findings suggest that acute
      psychosis is a potential adverse effect of antibiotic treatment of UTI, although
      the mechanism(s) underlying this association remains unclear. 

PMID- 24911442
TI  - A case of late-onset angioedema associated with clozapine and redevelopment of
      angioedema with olanzapine.

PMID- 24911443
TI  - Interaction of 5-HTT and HTR1A gene polymorphisms in treatment responses to
      mirtazapine in patients with major depressive disorder.
AB  - We tested for the association of HTR1A and 5-HTT genetic polymorphisms with
      treatment response to mirtazapine and evaluated the interactive effect between
      the polymorphisms in 283 patients with major depressive disorder. Korean subjects
      with diagnosis of major depressive disorder using the Structured Clinical
      Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition Axis I disorders were recruited. Clinical symptoms were evaluated using
      the 17-item Hamilton Depression Rating (HAMD-17) Scale at baseline and after 1,
      2, 4, 8, and 12 weeks of treatment with mirtazapine. The genetic association of 5
      HTTLPR and HTR1A+272G>A with treatment response was analyzed. We found a
      significant association of the 12.12-repeat genotype of 5-HTT various number
      tandem repeat (VNTR) with a large percentage decline in HAMD-17 Scale score after
      4, 8, and 12 weeks of treatment with mirtazapine. We also found that the
      frequency of the 12.12-repeat genotype was higher in responders than in
      nonresponders at week 8. The HTR1A+272GG genotype was significantly associated
      with a large percentage decline in HAMD-17 Scale score at 4, 8, and 12 weeks,
      although the genotypic frequencies were comparable between responders and
      nonresponders during the study period. Patients with the 12.12-repeat 5-HTT VNTR
      and GG of HTR1A+272G>A showed the highest HAMD-17 Scale percentage reduction
      during the study period and a better treatment response status after 4 weeks.
      These results suggest that the interaction between HTR1A+272G>A and 5-HTT VNTR is
      involved in the response to mirtazapine treatment and that a combination of these
      may be a useful marker for predicting treatment response to mirtazapine. 

PMID- 24911444
TI  - The meaning of brain death: a different view.

PMID- 24911445
TI  - Differential mortality in a long-living community in Sardinia (Italy): a cohort
      analysis.
AB  - The majority of studies on longevity in Sardinia point to an exceptional level of
      longevity, particularly for males, in this region of Italy. This study used
      individual data, considering selected groups of individuals such as centenarians,
      or focusing on cohorts of newborns in a large time period, that have previously
      been treated as a single group. An analysis on decennial birth cohorts from 1872
      to 1911 in a selected village located in the Blue Zone area of longevity in
      Sardinia was used to gain insight into sex differentials in mortality in this
      area of high longevity and to separate differences between cohorts' experiences,
      considering the possible role of significant events in determining differential
      mortality among them. The results show that there is not a secular trend in
      survival in the birth cohorts under study, but rather that several points of
      mortality convergence and crossover occur, which make the estimates derived from
      conventional sensitivity tests of survival curves unreliable. Differences among
      birth cohorts' experiences are more marked among the male population and at early
      adult ages. External events are shown to play a relevant role in mortality
      variations, despite not having an impact on the ageing process. The results
      highlight that, although there are not statistically significant differences
      between the two sexes, the male population is exposed to a higher risk of death
      and proves to be more vulnerable to external changes. This suggests that extreme
      contextual conditions, both favourable and unfavourable, may significantly affect
      the mortality trajectories of a population. 

PMID- 24911447
TI  - Ratiometric detection of nanomolar concentrations of heparin in serum and plasma
      samples using a fluorescent chemosensor based on peptides.
AB  - A peptidyl fluorescent chemosensor for heparin was synthesized by conjugating a
      pyrene fluorophore with the heparin-binding peptide. The fluorescent chemosensor
      (Py12; pyrene-RKRLQVQLSIRT) showed a highly sensitive ratiometric response to
      nanomolar concentrations of heparin in aqueous solutions at physiological pH by
      increasing excimer emission intensity at 500 nm with a concomitant decrease in
      monomer emission intensity at 400 nm. Py12 showed a sensitive ratiometric
      response to heparin over a wide pH range (1.5 <= pH <= 11.5) and exhibited high
      selectivity for heparin compared to other biological competitors, such as
      hyaluronic acid and chondroitin sulfate. Py12 sensitively and ratiometrically
      detected nanomolar concentrations of heparin in biologically relevant samples
      containing human serum and human plasma, respectively. The detection limit of
      Py12 was 34 pM (R(2) = 0.997) for heparin in an aqueous buffer solutions
      containing 5% human serum and 33 pM (R(2) = 0.994) for heparin in aqueous buffer
      solutions containing 5% human plasma. Py12 had sufficient sensitivity and
      selectivity for ratiometrically detecting a nanomolar concentration of heparin,
      indicating that the peptide-base chemosensor provides a potential tool for
      monitoring heparin levels in clinical plasma samples. 

PMID- 24911446
TI  - Choroidal Haller's and Sattler's layer thickness measurement using 3-dimensional
      1060-nm optical coherence tomography.
AB  - OBJECTIVES: To examine the feasibility of automatically segmented choroidal
      vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy
      and AMD eyes and by mapping Haller's and Sattler's layer thickness in healthy
      eyes. METHODS: Fifty-five eyes (from 45 healthy subjects and 10 with non
      neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D
      1060-nmOCT over a 36 degrees x36 degrees  field of view. Haller's and Sattler's
      layer were automatically segmented, mapped and averaged across the Early
      Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes,
      imaging was repeated within the same session and on another day. Outcomes were
      the repeatability agreement of Haller's and Sattler's layer thicknesses in
      healthy and AMD eyes, the validation with ICGA and the statistical analysis of
      the effect of age and axial eye length (AL) on both healthy choroidal sublayers.
      RESULTS: The coefficients of repeatability for Sattler's and Haller's layers were
      35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean+/
      SD healthy central submacular field thickness for Sattler's and Haller's was 87+/
      56 um and 141+/-50 um, respectively, with a significant relationship for AL
      (P<.001). CONCLUSIONS: Automated Sattler's and Haller's thickness segmentation
      generates rapid 3D measurements with a repeatability corresponding to reported
      manual segmentation. Sublayers in healthy eyes thinned significantly with
      increasing AL. In the presence of the thinned Sattler's layer in AMD, careful
      measurement interpretation is needed. Automatic choroidal vascular layer mapping
      may help to explain if pathological choroidal thinning affects medium and large
      choroidal vasculature in addition to choriocapillaris loss.

PMID- 24911448
TI  - Optically induced dielectropheresis sorting with automated medium exchange in an
      integrated optofluidic device resulting in higher cell viability.
AB  - We demonstrated the integration of a microfluidic device with an optically
      induced dielectrophoresis (ODEP) device such that the critical medium replacement
      process was performed automatically and the cells could be subsequently
      manipulated by using digitally projected optical images. ODEP has been
      demonstrated to generate sufficient forces for manipulating particles/cells by
      projecting a light pattern onto photoconductive materials which creates virtual
      electrodes. The production of the ODEP force usually requires a medium that has a
      suitable electrical conductivity and an appropriate dielectric constant.
      Therefore, a 0.2 M sucrose solution is commonly used. However, this requires a
      complicated medium replacement process before one is able to manipulate cells.
      Furthermore, the 0.2 M sucrose solution is not suitable for the long-term
      viability of cells. In comparison to conventional manual processes, our automated
      medium replacement process only took 25 minutes. Experimental data showed that
      there was up to a 96.2% recovery rate for the manipulated cells. More
      importantly, the survival rate of the cells was greatly enhanced due to this
      faster automated process. This newly developed microfluidic chip provided a
      promising platform for the rapid replacement of the cell medium and this was also
      the first time that an ODEP device was integrated with other active flow control
      components in a microfluidic device. By improving cell viability after cell
      manipulation, this design may contribute to the practical integration of ODEP
      modules into other lab-on-a-chip devices and biomedical applications in the
      future. 

PMID- 24911449
TI  - Site-specific rate constant measurements for primary and secondary H- and D
      abstraction by OH radicals: propane and n-butane.
AB  - Site-specific rate constants for hydrogen (H) and deuterium (D) abstraction by
      hydroxyl (OH) radicals were determined experimentally by monitoring the reaction
      of OH with two normal and six deuterated alkanes. The studied alkanes include
      propane (C3H8), propane 2,2 D2 (CH3CD2CH3), propane 1,1,1-3,3,3 D6 (CD3CH2CD3),
      propane D8 (C3D8), n-butane (n-C4H10), butane 2,2-3,3 D4 (CH3CD2CD2CH3), butane
      1,1,1-4,4,4 D6 (CD3CH2CH2CD3), and butane D10 (C4D10). Rate constant measurements
      were carried out over 840-1470 K and 1.2-2.1 atm using a shock tube and OH laser
      absorption. Previous low-temperature data were combined with the current high
      temperature measurements to generate three-parameter fits which were then used to
      determine the site-specific rate constants. Two primary (P1,H and P1,D) and four
      secondary (S00,H, S00,D, S01,H, and S01,D) H- and D-abstraction rate constants,
      in which the subscripts refer to the number of C atoms connected to the next
      nearest-neighbor C atom, are obtained. The modified Arrhenius expressions for the
      six site-specific abstractions by OH radicals are P1,H = 1.90 * 10(-18)T(2.00)
      exp(-340.87 K/T) cm(3) molecule(-1) s(-1) (210-1294 K); P1,D = 2.72 * 10(-17)
      T(1.60) exp(-895.57 K/T) cm(3) molecule(-1) s(-1) (295-1317 K); S00,H = 4.40 *
      10(-18) T(1.93) exp(121.50 K/T) cm(3) molecule(-1) s(-1) (210-1294 K); S00,D =
      1.45 * 10(-20) T(2.69) exp(282.36 K/T) cm(3) molecule(-1) s(-1) (295-1341 K);
      S01,H = 4.65 * 10(-17) T(1.60) exp(-236.98 K/T) cm(3) molecule(-1) s(-1) (235
      1407 K); S01,D = 1.26 * 10(-18) T(2.07) exp(-77.00 K/T) cm(3) molecule(-1) s(-1)
      (294-1412 K). 

PMID- 24911450
TI  - Impact of nonsynonymous mutations of factor X on the functions of factor X and
      anticoagulant activity of edoxaban.
AB  - Edoxaban is an oral direct factor Xa (FXa) inhibitor and its efficacy as an oral
      anticoagulant is less subject to drug-food and drug-drug interaction than
      existing vitamin K antagonists. Although this profile of edoxaban suggests it is
      well suited for clinical use, it is not clear whether genetic variations of
      factor X influence the activity of edoxaban. Our aim was to investigate a
      possible impact of single-nucleotide polymorphisms (SNPs) in the factor X gene on
      the functions of factor X and the activity of edoxaban. Two nonsynonymous SNPs
      within mature factor X, Ala152Thr and Gly192Arg, were selected as possible
      candidates that might affect the functions of FXa and the activity of edoxaban.
      We measured catalytic activities of wild type and mutant FXas in a chromogenic
      assay using S-2222 and coagulation times including prothrombin time (PT) and
      activated partial thrombin time (aPTT) of plasma-containing recombinant FXs in
      the presence and absence of edoxaban. Michaelis-Menten kinetic parameters of
      FXas, Km and Vmax values, PT and aPTT were not influenced by either mutation
      indicating these mutations do not affect the FXa catalytic and coagulation
      activities. The Ki values of edoxaban for the FXas and the concentrations of
      edoxaban required to double PT and aPTT were not different between wild type and
      mutated FXas indicating that both mutations have little impact on the activity of
      edoxaban. In conclusion, these data suggest that edoxaban has little interpatient
      variability stemming from SNPs in the factor X gene. 

PMID- 24911451
TI  - Recurrent acute myocardial infarction as an initial manifestation of
      antiphospholipid syndrome: treatment and management.
AB  - The antiphosholipid syndrome (APS) is an autoimmune disorder, characterized by
      the presence of vascular thrombosis and/or pregnancy morbidity in a patient with
      positive laboratory tests for antiphospholipid antibodies. The patients with APS
      are in the high risk of rethrombosis. We report the case of 43-year-old female
      presenting with recurrent acute myocardial infarction with ST-segment elevation
      because of recurrent coronary thrombosis in coronary left anterior descending
      artery (LAD) and circumflex coronary artery (Cx) resulting in four percutaneous
      coronary interventions (PCI), associated with the presence of plasma
      antiphospholipid antibodies. Patient received seven stents to LAD and the
      aspiration of thrombus from Cx artery was performed. Pharmacotherapy included
      full antithrombotic treatment consisted with antiplatelet drugs such as: aspirin,
      clopidogrel followed by prasugrel, glycoprotein IIb/IIIa receptor antagonists and
      anticoagulants such as heparin followed by warfarin as well as steroids. At 1
      year follow-up, controlled coronary angiography confirmed the good effect of PCI
      without any signs of stenosis or rethrombosis and highlighted the important role
      of antithrombotic treatment in patients with APS. 

PMID- 24911452
TI  - Fibrinolysis status in the Budd-Chiari syndrome in China.
AB  - Pathogenesis and clinical characteristics of the Budd-Chiari syndrome (BCS) in
      Asia are somewhat different from the ones observed in Western countries.
      Obstruction of the inferior vena cava (IVC) or of the hepatic veins is caused to
      a greater extent by membranous webs than by thrombosis. Impaired fibrinolysis has
      been found in European patients with BCS, but its status in Chinese patients with
      this condition is still unknown. To explore the characteristics of fibrinolysis
      in BCS patients in this country, we measured the euglobulin lysis time (ELT) for
      overall fibrinolysis and the plasma levels of five fibrinolytic components in 65
      Chinese patients with BCS and 43 healthy controls. In patients, ELTs were
      slightly shorter than in controls (mean, 293 vs. 357 min, P < 0.02), tissue type
      plasminogen activator levels were higher than in controls (mean, 239 vs. 185
      pg/ml, P < 0.01), and plasminogen activator inhibitor 1 levels were lower than in
      controls (mean, 1.43 vs. 1.73 ng/ml, P < 0.001). To explore BCS in more detail,
      we subgrouped the cases according to age, type of venous occlusion, Child-Pugh
      score, and thrombosis. As a result of this analysis, we found that young patients
      (age <30 years) had a longer ELT (mean, 440 min) than the older patient groups
      (30 <= age <= 44, 45 <= age <= 54, age>54 years; mean ELT = 242, 198, and 289
      min, respectively, all P < 0.05). The independent hepatic vein occlusion subgroup
      showed a longer ELT (mean, 367 min) than the combined hepatic vein and IVC or the
      independent IVC occlusion subgroup (mean ELT = 233 and 260 min, both P < 0.05).
      ELT did not show significant differences between Child-Pugh class A and B
      subgroups (mean, 267 vs. 333 min, P > 0.05). ELT in the subgroup without
      thrombosis was shorter than in controls (mean, 288 vs. 358 min, P < 0.05), and in
      the subgroup with thrombosis, it was also slightly shorter than in controls,
      without reaching statistical significance (mean, 306 vs. 358 min, P > 0.05). By
      and large, overall fibrinolytic potential was slightly increased in Chinese
      patients with BCS in this study, but fibrinolysis differed according to its
      baseline characteristics. Compared with the one seen in BCS patients from Western
      countries, BCS in China exhibits certain special changes in fibrinolysis and we
      were able to explain some of these changes.

PMID- 24911453
TI  - B-cell-activating factor, a proliferation inducing ligand and co-stimulatory
      molecules in the pathogenesis of immune thrombocytopenia in childhood.
AB  - The aim of this study was to measure the levels of B-cell-activating factor
      (BAFF), a proliferation-inducing ligand (APRIL), and co-stimulatory molecules in
      immune thrombocytopenia (ITP) of childhood to investigate the interaction between
      T and B lymphocytes and the impact of proliferation of B lymphocytes in the
      pathogenesis. Twenty newly diagnosed ITPs, 20 chronic ITPs, and 20 healthy
      controls between 2 and 18 years were enrolled in this study. Hemogram, BAFF,
      APRIL, interleukin-4, and interferon (IFN)-gamma levels in sera and expressions
      of CD19, CD 3, CD21, CD40, and CD 154 on leukocytes were measured by ELISA and
      flow cytometry. Mean BAFF level in newly diagnosed ITP group was higher than the
      mean BAFF level in other groups. BAFF levels were significantly decreased after
      the treatment in newly diagnosed ITP group. APRIL, interleukin-4, and IFN-gamma
      in newly diagnosed ITP group and BAFF, APRIL, interleukin-4, and IFN-gamma in
      chronic ITP group were similar before and after treatment. There was no
      statistical difference for expressions of CD 19 and CD3 on lymphocytes, CD40 on
      leukocytes, CD154 on T cells, and for percentages of CD21/CD40, CD21/CD40,
      CD21/CD40 B cells, and CD19/CD3 lymphocytes for pretreatment and posttreatment
      levels in both ITP groups. In conclusion, our study strongly demonstrated that
      BAFF has an important role in the pathogenesis of newly diagnosed childhood ITP.
      It may be important in the follow-up and in novel therapy modalities of these
      patients. 

PMID- 24911454
TI  - Acquired von Willebrand disease and multiple myeloma: a case report of a breast
      cancer survivor.
AB  - Acquired von Willebrand disease (aVWD) is rare disease and is associated with a
      variety of underlying diseases. We report a case of aVWD in the setting of
      multiple myeloma. The patient was a 63-year-old female with breast cancer in
      remission who was admitted for symptomatic anemia. She was diagnosed with
      multiple myeloma. She also had subcutaneous bleeding before admission. Laboratory
      studies revealed isolated prolongation of the activated partial thromboplastin
      time, which corrected in a mixing study. Her factor VIII activity, von Willebrand
      factor (VWF) Ag, and VWF activity were low. VWF multimer study confirmed the
      patient had aVWD. The treatment of aVWD is discussed in this article, including
      the treatment of underlying diseases, and acute management in emergent
      situations. An intriguing question in this case is whether the patient's multiple
      myeloma is a chemotherapy-induced hematological malignancy or a second primary
      malignancy. 

PMID- 24911455
TI  - The relationship between platelet to lymphocyte ratio and the clinical outcomes
      in ST elevation myocardial infarction underwent primary coronary intervention.
AB  - The platelet to lymphocyte ratio (PLR) has been investigated as a new predictor
      for cardiovascular risk. The aim of the present study was to investigate the
      prognostic role admission PLRat admission in predicting in-hospital and early
      mortality in patients presenting with ST segment elevation myocardial infarction
      (STEMI). A total of 639 consecutive patients with STEMI who underwent primary
      percutaneous coronary intervention (PCI) were included. The study population was
      divided into tertiles on the basis of PLR values at the admission. A high PLR (N
      = 213) was defined as a value in the upper third tertile (PLR >174.9) and a low
      PLR (N = 426) was defined as any value in the lower two tertiles (PLR <= 174.9).
      The patients were followed for clinical outcomes for up to 6 months after
      discharge. In Kaplan-Meier survival analysis, the rate of 6-month all-cause
      deaths was 7% in the high PLR group versus 3% in the low PLR group (P = 0.03). In
      multivariate analyses, a significant association was noted between high PLR
      levels and the adjusted risk of 6-month all-cause deaths (odds ratio = 2.51, 95%
      confidence interval = 1.058-5.95; P = 0.03). PLR is a readily available clinical
      laboratory value associated with 6-month all-cause death in patients with STEMI
      who undergo primary PCI.

PMID- 24911456
TI  - Lung cancer chemotherapy agents increase procoagulant activity via protein
      disulfide isomerase-dependent tissue factor decryption.
AB  - Lung cancer patients undergoing chemotherapy have an elevated risk for
      thrombosis. However, the mechanisms by which chemotherapy agents increase the
      risk for thrombosis remains unclear. The aim of this study was to determine the
      mechanism(s) by which lung cancer chemotherapy agents cisplatin, carboplatin,
      gemcitabine, and paclitaxel elicit increased tissue factor activity on
      endothelial cells, A549 cells, and monocytes. Tissue factor activity, tissue
      factor antigen, and phosphatidylserine exposure were measured on chemotherapy
      treated human umbilical vein endothelial cells (HUVEC), A549 cells, and
      monocytes. Cell surface protein disulfide isomerase (PDI) and cell surface free
      thiol levels were measured on HUVEC and A549 non-small cell lung carcinoma cells.
      Treatment of HUVECs, A549 cells, and monocytes with lung cancer chemotherapy
      significantly increased cell surface tissue factor activity. However, elevated
      tissue factor antigen levels were observed only on cisplatin-treated and
      gemcitabine-treated monocytes. Cell surface levels of phosphatidylserine were
      increased on HUVEC and monocytes treated with cisplatin/gemcitabine combination
      therapy. Chemotherapy also resulted in increased cell surface levels of PDI and
      reduced cell surface free thiol levels. Glutathione treatment and PDI inhibition,
      but not phosphatidylserine inhibition, attenuated tissue factor activity.
      Furthermore, increased tissue factor activity was reversed by reducing cysteines
      with dithiothreitol. These studies are the first to demonstrate that lung cancer
      chemotherapy agents increase procoagulant activity on endothelial cells and A549
      cells by tissue factor decryption through a disulfide bond formation in a PDI
      dependent mechanism. 

PMID- 24911457
TI  - The significance of F139V mutation on thrombotic events in compound heterozygous
      and homozygous protein C deficiency.
AB  - Both compound heterozygous and homozygous protein C deficiencies (PCDs) can cause
      lethal thrombotic events in children. This study investigated the significance of
      F139V mutation in activation of protein C in heterozygous and biallelic PCD. Two
      pedigrees with three probands were recruited, including heterozygous, compound
      heterozygous, and homozygous PCD and non-PCD families. The plasma levels of
      protein C activity (PC:A), protein C antigen (PC:Ag), factor V:C, factor VIII:C,
      fibrinogen (FIB), and D-dimer (D-D) were measured. Prothrombin time (PT),
      activated partial thromboplastin time (APTT), and thrombin time (TT) were also
      detected. All nine exons of protein C gene (PROC) were sequenced. Protein C
      mutation, T>G at site 6128 (exon 7) resulting in F139V, was identified in both
      pedigrees. Heterozygous missense mutation F139V (n = 10) had 56.4% lower levels
      of PC:A and PC:Ag compared with members with wild-type PROC (n = 6). Biallelic
      compound heterozygous and homozygous PCDs with F139V (n = 3) significantly
      decreased the levels of PC:A and PC:Ag compared with heterozygous members (P <
      0.05); however, these were not lethal. Heterozygous F139V mutations of PRO caused
      mild reduction of protein C function, which might be the reason for survival of
      compound heterozygous or homozygous PCD with F139V in adults.

PMID- 24911458
TI  - Lymphocyte subsets in primary immune thrombocytopenia.
AB  - The aim of this study was to explore the clinical significance of T-lymphocyte
      subsets in the peripheral blood of patients with adult primary immune
      thrombocytopenia (ITP) in an active phase. T-lymphocyte subsets in the peripheral
      blood of 90 ITP patients in the active phase and 59 normal controls were detected
      by flow cytometry. ITP patients were treated with a conventional dose of
      corticosteroids, and therapeutic response was evaluated after 3 months. The level
      of CD4 T lymphocytes (35.7 +/- 4.6%) and natural killer cells (13.1 +/- 2.1%) in
      the active ITP patients was lower compared with the control group (40.4 +/- 3.7%
      and 23.2 +/- 1.1%, respectively, P < 0.05 for both). The level of CD8 T
      lymphocytes (30.11 +/- 4.50%) in ITP showed a significantly wider distribution
      than that in the normal controls (25.5 +/- 5.91%, P < 0.05). Additionally, the
      patients with higher levels of CD4 T cells were less likely to respond to
      corticosteroids (r = 0.69, P = 0.04). The detection of immunocyte subsets might
      be helpful for the ITP patients concerning their diagnosis and determination of
      therapeutic outcome.

PMID- 24911459
TI  - Desmopressin responsiveness at a capped dose of 15  MUg in type 1 von Willebrand
      disease and mild hemophilia A.
AB  - Desmopressin (DDAVP) is commonly used in the treatment of patients with type 1
      von Willebrand disease (VWD) and mild hemophilia A. A patient's responsiveness to
      DDAVP based on a 0.3  MUg/kg dose determines future therapeutic efficacy of the
      drug. The aim of the study was to determine whether a capped dose of 15 MUg
      subcutaneous DDAVP is able to achieve the same level of DDAVP responsiveness as
      previously reported. This is a retrospective chart review of patients from 1995
      to 2013 in adults and children with type 1 VWD and hemophilia A weighing more
      than 50 kg. Levels of factor VIII, ristocetin cofactor, and von Willebrand factor
      antigen were measured before and after 1 h of administration of 15 MUg of DDAVP.
      In patients with type 1 VWD, the complete response rate was 82.5% with a partial
      response rate of 12.5% and 5% nonresponders. In patients with mild hemophilia A,
      the complete response rate was 53.8% with a partial response rate of 38.5% and
      7.7% nonresponders. These results using a capped 15-MUg dose of DDAVP are similar
      to previously published reports using the 0.3-MUg/kg dose.

PMID- 24911460
TI  - Plant volatile analogues strengthen attractiveness to insect.
AB  - Green leaf bug Apolygus lucorum (Meyer-Dur) is one of the major pests in
      agriculture. Management of A. lucorum was largely achieved by using pesticides.
      However, the increasing population of A. lucorum since growing Bt cotton widely
      and the increased awareness of ecoenvironment and agricultural product safety
      makes their population-control very challenging. Therefore this study was
      conducted to explore a novel ecological approach, synthetic plant volatile
      analogues, to manage the pest. Here, plant volatile analogues were first designed
      and synthesized by combining the bioactive components of beta-ionone and
      benzaldehyde. The stabilities of beta-ionone, benzaldehyde and analogue 3 g were
      tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to
      the analogues were recorded. And the behavior assay and filed experiment were
      also conducted. In this study, thirteen analogues were acquired. The analogue 3 g
      was demonstrated to be more stable than beta-ionone and benzaldehyde in the
      environment. Many of the analogues elicited EAG responses, and the EAG response
      values to 3 g remained unchanged during seven-day period. 3 g was also
      demonstrated to be attractive to A. lucorum adults in the laboratory behavior
      experiment and in the field. Its attractiveness persisted longer than beta-ionone
      and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect
      and has potential as an attractant. Our results suggest that synthetic plant
      volatile analogues can strengthen attractiveness to insect. This is the first
      published study about synthetic plant volatile analogues that have the potential
      to be used in pest control. Our results will support a new ecological approach to
      pest control and it will be helpful to ecoenvironment and agricultural product
      safety. 

PMID- 24911461
TI  - Prevalence and causes of elevated serum aminotransferase levels in a population
      based cohort of persons with chronic hepatitis B virus infection.
AB  - BACKGROUND & AIMS: Information delineating the possible causes for elevated serum
      aminotransferase activity among persons with chronic hepatitis B virus (HBV)
      infection is limited. METHODS: We analysed data collected from a population-based
      cohort of persons with chronic HBV infection followed from 2001 to 2010 to
      determine the frequency and causes of elevated aminotransferase activity. Any
      elevation concurrent with an HBV DNA level ?2000 IU/ml was attributed to immune
      active hepatitis B. Participant medical charts were reviewed by expert clinical
      staff to determine the presence of additional or alternative attributable causes.
      For each participant, a serum aminotransferase elevation could be attributed to
      more than one cause. RESULTS: Among 1090 persons with chronic HBV infection, the
      mean follow-up was 7.7 years and the median age in 2001 was 39 (range 19-96)
      years; 634 (58.2%) had ?1 elevated aminotransferase level during follow-up and
      438 (69.1%) of persons with ?1 elevation had at least one cause assigned for the
      elevation. The most common causes of aminotransferase elevations were immune
      active hepatitis B (48.4%), alcohol consumption (30.8%), and non-alcoholic fatty
      liver disease (NAFLD) (24.7%). Among participants with HBV DNA levels
      persistently less than 2000 IU/ml, the most common causes were NAFLD or alcohol
      consumption. CONCLUSIONS: In this population-based cohort of persons with chronic
      HBV infection, the prevalence of elevated aminotransferase activity was high and
      attributable to immune active chronic hepatitis B in approximately half of the
      cases; however, NAFLD or alcohol consumption were also common causes for enzyme
      elevations. These findings underscore the importance of monitoring HBV DNA
      levels, in addition to aminotransferase activity, among persons with chronic HBV
      infection so that appropriate interventions, including antiviral therapy, are
      utilised.

PMID- 24911464
TI  - Beyond the schools of psychology 2: a digital analysis of psychological review,
      1904-1923.
AB  - In order to better understand the broader trends and points of contention in
      early American psychology, it is conventional to organize the relevant material
      in terms of "schools" of psychology-structuralism, functionalism, etc. Although
      not without value, this scheme marginalizes many otherwise significant figures,
      and tends to exclude a large number of secondary, but interesting, individuals.
      In an effort to address these problems, we grouped all the articles that appeared
      in the second and third decades of Psychological Review into five-year blocks,
      and then cluster analyzed each block by the articles' verbal similarity to each
      other. This resulted in a number of significant intellectual "genres" of
      psychology that are ignored by the usual "schools" taxonomy. It also made
      "visible" a number of figures who are typically downplayed or ignored in
      conventional histories of the discipline, and it provide us with an intellectual
      context in which to understand their contributions. 

PMID- 24911467
TI  - Rotation of a bulky triptycene in the solid state: toward engineered nanoscale
      artificial molecular machines.
AB  - We report the design and dynamics of a solid-state molecular rotor with a large
      triptycene rotator. With a cross-section and surface area that are 2 and 3 times
      larger than those of the phenylene rotators previously studied in the solid
      state, it is expected that van der Waals forces and steric hindrance will render
      the motion of the larger triptycene more difficult. To address this challenge, we
      used a rigid and shape-persistent stator in a dendritic structure that reaches
      ca. 3.6 nm in length. Using variable-temperature solid-state (2)H NMR
      spectroscopy, we determined a symmetric three-fold rotational potential with a
      barrier of 10.2 kcal/mol and a pre-exponential factor of 1.1 * 10(10) s(-1),
      which correspond to ca. 4600 Brownian jumps per second in the solid state at 300
      K. 

PMID- 24911462
TI  - Vascular pathobiology in chronic liver disease and cirrhosis - current status and
      future directions.
AB  - Chronic liver disease is associated with remarkable alterations in the intra- and
      extrahepatic vasculature. Because of these changes, the fields of liver
      vasculature and portal hypertension have recently become closely integrated
      within the broader vascular biology discipline. As developments in vascular
      biology have evolved, a deeper understanding of vascular processes has led to a
      better understanding of the mechanisms of the dynamic vascular changes associated
      with portal hypertension and chronic liver disease. In this context, hepatic
      vascular cells, such as sinusoidal endothelial cells and pericyte-like hepatic
      stellate cells, are closely associated with one another, where they have
      paracrine and autocrine effects on each other and themselves. These cells play
      important roles in the pathogenesis of liver fibrosis/cirrhosis and portal
      hypertension. Further, a variety of signaling pathways have recently come to
      light. These include growth factor pathways involving cytokines such as
      transforming growth factor beta, platelet derived growth factor, and others as
      well as a variety of vasoactive peptides and other molecules. An early and
      consistent feature of liver injury is the development of an increase in intra
      hepatic resistance; this is associated with changes in hepatic vascular cells and
      their signaling pathway that cause portal hypertension. A critical concept is
      that this process aggregates signals to the extrahepatic circulation, causing
      derangement in this system's cells and signaling pathways, which ultimately leads
      to the collateral vessel formation and arterial vasodilation in the splanchnic
      and systemic circulation, which by virtue of the hydraulic derivation of Ohm's
      law (pressure = resistance * flow), worsens portal hypertension. This review
      provides a detailed review of the current status and future direction of the
      basic biology of portal hypertension with a focus on the physiology,
      pathophysiology, and signaling of cells within the liver, as well as those in the
      mesenteric vascular circulation. Translational implications of recent research
      and the future directions that it points to are also highlighted.

PMID- 24911465
TI  - A general NMR-based strategy for the in situ characterization of sugar-nucleotide
      dependent biosynthetic pathways.
AB  - A simple method for the study of sugar-nucleotide-dependent multienzyme cascades
      is highlighted where the use of selectively (13)C-labeled sugar nucleotides and
      inverse (13)C detection NMR offers fast, direct detection and quantification of
      reactants and products and circumvents the need for chromatographic separation.
      The utility of the method has been demonstrated by characterizing four previously
      uncharacterized sugar nucleotide biosynthetic enzymes involved in calicheamicin
      biosynthesis. 

PMID- 24911463
TI  - Strategies for immortalization of primary hepatocytes.
AB  - The liver has the unique capacity to regenerate in response to a damaging event.
      Liver regeneration is hereby largely driven by hepatocyte proliferation, which in
      turn relies on cell cycling. The hepatocyte cell cycle is a complex process that
      is tightly regulated by several well-established mechanisms. In vitro, isolated
      hepatocytes do not longer retain this proliferative capacity. However, in vitro
      cell growth can be boosted by immortalization of hepatocytes. Well-defined
      immortalization genes can be artificially overexpressed in hepatocytes or the
      cells can be conditionally immortalized leading to controlled cell proliferation.
      This paper discusses the current immortalization techniques and provides a state
      of-the-art overview of the actually available immortalized hepatocyte-derived
      cell lines and their applications. 

PMID- 24911468
TI  - Strategies for the biofunctionalization of gold and iron oxide nanoparticles.
AB  - The field of nanotechnology applied to medicine (nanomedicine) is developing at a
      fast pace and is expected to provide solutions for early diagnosis, targeted
      therapy, and personalized medicine. However, designing nanomaterials for
      biomedical applications is not a trivial task. Avoidance of the immune system,
      stability in physiological media, control over the interaction of a nanomaterial
      with biological entities such as proteins and cell membranes, low toxicity, and
      optimal bioperformance are critical for the success of the designed nanomaterial.
      In this Feature Article we provide a concise overview of some of the most recent
      advances concerning the derivatization of gold and iron oxide nanoparticles for
      bioapplications. The most important aspects relating to the functionalization of
      gold and iron oxide nanoparticles with carbohydrates, peptides, nucleic acids,
      and antibodies are covered, highlighting the recent contributions from our
      research group. We suggest tips for the appropriate (bio)functionalization of
      these inorganic nanoparticles in order to preserve the biological activity of the
      attached biomolecules and ensure their subsequent stability in physiological
      media. 

PMID- 24911469
TI  - Magnetic relaxation versus 3D long-range ordering in {Dy2Ba(alpha-fur)8}n furoate
      polymers.
AB  - A novel Dy-complex formulated as {[Dy2Ba(alpha-C4H3OCOO)8.(H2O)4].2H2O}n,
      {Dy2Ba(alpha-fur)8}n, has been synthesized, structurally characterized, and
      magnetically and thermally investigated as a function of field and temperature,
      down to 85 mK. The alpha-furoate ligands consolidate 1D zig-zag chains formed by
      Dy2 dimers separated by Ba ions. Ab initio calculations were used to determine
      the easy anisotropy axis direction, the gyromagnetic tensor components and the
      energy levels of each Dy. The heat capacity and susceptibility measurements
      allowed us to conclude that intradimer and interdimer interactions are
      ferromagnetic and of the same order, J'/k(B) ~ J''/k(B) = +0.55 K. In the absence
      of an applied magnetic field, the dynamic relaxation of the magnetization occurs
      through the fast (tau(T) ~ 10(-5) s) spin-reversal of each of the individual Dys
      through a quantum tunneling (QT) process. A long-range 3D ordered state is
      achieved at T(N) = 0.25 K, in which the ferromagnetically coupled zig-zag chains
      (J'/k(B) ~ J''/k(B) = +0.528(1) K) running along the c-axis are
      antiferromagnetically coupled to the adjacent chains (J'''/k(B) = -0.021(1) K).
      Critical slowing down of the QT time constant is observed when the temperature
      approaches T(N). Under the application of a magnetic field, the QT relaxation is
      replaced by an Orbach process (with energy barrier U/k(B) = 68 K and tau0 ~ 10(
      9) s at H = 2 kOe) and a very slow (tau(s) ~ 0.2 s) relaxation process. We
      propose and demonstrate the proof of concept of a spintronic device, in which two
      different relaxation rates can be selected, and on/off switched by magnetic field
      biasing. The dynamical behavior of this compound is compared with another furoate
      to discuss the effect of competitive interactions.

PMID- 24911471
TI  - Lymphomatoid papulosis type C of the eyelid in a young girl: a case report and
      review of literature.
AB  - PURPOSE: To report an unusual presentation of a case of Lymphomatoid
      papulosis(LyP) in a young girl. MATERIAL AND METHODS: A 14-year-old female
      presented with a history of swelling of the left upper eyelid of two weeks
      duration. There was a history of trivial trauma prior to the swelling. The
      patient was diagnosed as having pre-septal cellulitis elsewhere and was put on
      oral antibiotics. The lesion was non-responsive to oral antibiotics. The patient
      was then referred to our hospital. Ocular examination revealed an elevated lesion
      measuring 15 mm * 10 mm on the left upper eyelid, associated with pre-septal
      swelling and induration. Ocular movements were normal. The anterior and posterior
      segment examination was normal. Incision biopsy was done from the eyelid lesion.
      Multiple cutaneous lesions were also biopsied. RESULTS: The histopathology
      examination confirmed the diagnosis of lymphomatoid papulosis type C.
      Dermatological and systemic evaluation ruled out the other aggressive forms of
      CD30(+) lymphoid proliferation. CONCLUSION: We report an unusual presentation of
      lymphomatoid papulosis(LyP) type C in a young girl. Complete systemic work up and
      histopathological evaluation is mandatory in cases of suspicious lesions, not
      responding to conservative treatment.

PMID- 24911472
TI  - Multiplexed MRM with Internal Standards for Cerebrospinal Fluid Candidate Protein
      Biomarker Quantitation.
AB  - Multiplexed quantitation is essential for discovering, verifying, and validating
      biomarkers for risk stratification, disease prognostication, and therapeutic
      monitoring. The most promising strategy for quantifying unverified protein
      biomarkers in biofluids relies on selected/multiple reaction monitoring (SRM or
      MRM) technology with isotopically labeled standards employed within a bottom-up
      proteomic workflow. Since cerebrospinal fluid (CSF) is an important fluid for
      studying central nervous system (CNS) related diseases, we sought to develop a
      rapid, antibody- and fractionation-free MRM-based approach with a complex mixture
      of peptide standards to quantify a highly multiplexed panel of candidate protein
      biomarkers in human CSF. Development involved peptide transition optimization,
      denaturation/digestion protocol evaluation, transition interference screening,
      and protein quantitation via peptide standard curves. The final method exhibited
      excellent reproducibility (average coefficient of variation of <1% for retention
      time and <6% for signal) and breadth of quantitation (130 proteins from 311
      interference-free peptides) in a single 43-min run. These proteins are of high-to
      low abundance with determined concentrations from 118 MUg/mL (serum albumin) to
      550 pg/mL (apolipoprotein C-I). Overall, the method consists of the most highly
      multiplexed and broadest panel of candidate protein biomarkers in human CSF
      reported thus far and is well suited for subsequent verification studies on
      patient samples.

PMID- 24911470
TI  - Sources of fine particulate matter and risk of preterm birth in Connecticut, 2000
      2006: a longitudinal study.
AB  - BACKGROUND: Previous studies have examined fine particulate matter (<= 2.5 MUm;
      PM2.5) and preterm birth, but there is a dearth of longitudinal studies on this
      topic and a paucity of studies that have investigated specific sources of this
      exposure. OBJECTIVES: Our aim was to assess whether anthropogenic sources are
      associated with risk of preterm birth, comparing successive pregnancies to the
      same woman. METHODS: Birth certificates were used to select women who had vaginal
      singleton live births at least twice in Connecticut during 2000-2006 (n = 23,123
      women, n = 48,208 births). We procured 4,085 daily samples of PM2.5 on Teflon
      filters from the Connecticut Department of Environmental Protection for six
      cities in Connecticut. Filters were analyzed for chemical composition, and
      Positive Matrix Factorization was used to determine contributions of PM2.5
      sources. Risk estimates were calculated with conditional logistic regression,
      matching pregnancies to the same women. RESULTS: Odds ratios of preterm birth per
      interquartile range increase in whole pregnancy exposure to dust, motor vehicle
      emissions, oil combustion, and regional sulfur PM2.5 sources were 1.01 (95% CI:
      0.93, 1.09), 1.01 (95% CI: 0.92, 1.10), 1.00 (95% CI: 0.89, 1.12), and 1.09 (95%
      CI: 0.97, 1.22), respectively. CONCLUSION: This was the first study of PM2.5
      sources and preterm birth, and the first matched analysis, that better addresses
      individual-level confounding potentially inherent in all past studies. There was
      insufficient evidence to suggest that sources were statistically significantly
      associated with preterm birth. However, elevated central estimates and previously
      observed associations with mass concentration motivate the need for further
      research. Future studies would benefit from high source exposure settings and
      longitudinal study designs, such as that adopted in this study.

PMID- 24911473
TI  - Best-kept secrets.

PMID- 24911474
TI  - Sovaldi makes blockbuster history, ignites drug pricing unrest.

PMID- 24911475
TI  - Twitter storm forces Chimerix's hand in compassionate use request.

PMID- 24911477
TI  - First PDE4 inhibitor for psoriasis hits the market but impact is uncertain.

PMID- 24911482
TI  - Taiwan biotech buoyed by colossal financings.

PMID- 24911485
TI  - China's watchdog clamps down on genome sequencing services.

PMID- 24911486
TI  - First rounders podcast: Leroy Hood.

PMID- 24911487
TI  - University biotech patenting 2013.

PMID- 24911488
TI  - Diagnostics as the first line of defense in global health security.

PMID- 24911489
TI  - Expanding rare disease drug trials based on shared molecular etiology.

PMID- 24911490
TI  - The International Cancer Genome Consortium's evolving data-protection policies.

PMID- 24911491
TI  - The nature of Asian biopharmaceutical innovation.

PMID- 24911493
TI  - Behind closed doors.

PMID- 24911492
TI  - Metabolomic data streaming for biology-dependent data acquisition.

PMID- 24911494
TI  - Patents as proxies: NIH hubs of innovation.

PMID- 24911496
TI  - Inducing definitive hematopoiesis in a dish.

PMID- 24911497
TI  - Chemical safety without animals.

PMID- 24911498
TI  - RNA sequencing in situ.

PMID- 24911506
TI  - Mission possible: putting trainees at the center of academia's mission.

PMID- 24911508
TI  - Narratives of continuity among older people with late stage chronic kidney
      disease who decline dialysis.
AB  - Chronic and life-threatening conditions are widely thought to shatter the lives
      of those affected. In this article, we examine the accounts of 19 older people
      diagnosed with late stage chronic kidney disease who declined dialysis. Accounts
      were collected through in-depth interview in the United Kingdom (March-November,
      2010). Drawing on a phenomenological approach, we focus particularly on the
      embodied and lived experience of the condition and on how participants
      constructed treatment modalities and approached treatment choice. We look toward
      contemporary elaborations of the conceptual framework of biographical disruption
      to illustrate how participants managed to contain the intrusion of illness and
      maintain continuity in their lives. We argue that three interactive phenomena
      mitigated the potential for disruption and allowed participants to maintain
      continuity: (a) the framing of illness as "old age"; (b) the prior experience of
      serious illness; and (c) the choice of the treatment with the least potential for
      disruption. We conclude that a diagnosis of chronic illness in late life does not
      inevitably shatter lives or engender biographical disruption. Instead, people are
      able to construct continuity owing to complex narrative interpretations of
      diagnosis, sensation and treatment choices. 

PMID- 24911500
TI  - The Synthetic Biology Open Language (SBOL) provides a community standard for
      communicating designs in synthetic biology.
AB  - The re-use of previously validated designs is critical to the evolution of
      synthetic biology from a research discipline to an engineering practice. Here we
      describe the Synthetic Biology Open Language (SBOL), a proposed data standard for
      exchanging designs within the synthetic biology community. SBOL represents
      synthetic biology designs in a community-driven, formalized format for exchange
      between software tools, research groups and commercial service providers. The
      SBOL Developers Group has implemented SBOL as an XML/RDF serialization and
      provides software libraries and specification documentation to help developers
      implement SBOL in their own software. We describe early successes, including a
      demonstration of the utility of SBOL for information exchange between several
      different software tools and repositories from both academic and industrial
      partners. As a community-driven standard, SBOL will be updated as synthetic
      biology evolves to provide specific capabilities for different aspects of the
      synthetic biology workflow. 

PMID- 24911509
TI  - Patient and provider perspectives on quality and health system effectiveness in a
      transition economy: evidence from Ukraine.
AB  - Facing a severe population health crisis due to noncommunicable diseases, Ukraine
      and other former Soviet republics and Eastern European countries have a pressing
      need for more effective health systems. Policies to enhance health system
      effectiveness should consider the perspectives of different stakeholder groups,
      including providers as well as patients. In addition, policies that directly
      target the quality of clinical care should be based on objective performance
      measures. In 2009 and 2010 we conducted a coordinated series of household and
      facility-level surveys to capture the perspectives of Ukrainian household
      members, outpatient clinic patients, and physicians regarding the country's
      health system overall, as well as the quality, access, and affordability of
      health care. We objectively measured the quality of care for heart failure and
      chronic obstructive pulmonary disease using CPV((r)) vignettes. There was broad
      agreement among household respondents (79%) and physicians (95%) that Ukraine's
      health system should be reformed. CPV((r)) results indicate that the quality of
      care for common noncommunicable diseases is poor in all regions of the country
      and in hospitals as well as polyclinics. However, perspectives about the quality
      of care differ, with household respondents seeing quality as a serious concern,
      clinic patients having more positive perceptions, and physicians not viewing
      quality as a reform priority. All stakeholder groups viewed affordability as a
      problem. These findings have several implications for policies to enhance health
      system effectiveness. The shared desire for health system reform among all
      stakeholder groups provides a basis for action in Ukraine. Improving quality,
      strengthening primary care, and enhancing affordability should be major goals of
      new health policies. Policies to improve quality directly, such as pay-for
      performance, would be mutually reinforcing with purchasing reforms such as
      transparent payment mechanisms. Such policies would align the incentives of
      physicians with the desires of the population they serve. 

PMID- 24911510
TI  - Exploring lay views on physical activity and their implications for public health
      policy. A case study from East Belfast.
AB  - It is now recognised that inactive lifestyles underpin much of the disease burden
      evident in the richer nations of the world. Indeed, the WHO has identified
      physical inactivity as a 'global public health problem' and has established
      minimum physical activity (PA) targets for people at different stages of the life
      course. Yet, according to WHO, just under 1/3 of working age adults across the
      globe meet those targets and it is not at all clear how the disjunction between
      the recommendations of policy makers and the behaviour of ordinary people might
      be surmounted. Using an opportunity to examine the impact of an urban
      regeneration project on community residents in East Belfast (Northern Ireland)
      this paper examines the views of some 113 people on how to increase rates of PA
      in an area of multiple deprivation. The results of the analysis suggest that lay
      people rarely consider PA as a discrete issue, or one that centres on individuals
      and their motivation, but rather as one component in a complex web of concerns,
      processes and events that include such things as the actions of neighbours and
      relatives, material and political environments, vandalism, violence, and the
      weather. We explore and unravel the nature of those concerns using novel methods
      of content analysis that generate 'issue webs'. Particular attention is paid to
      the ways in which lay people conceptualize 'activity' and to the manner in which
      they point to ways of encouraging activity that are rooted in everyday life
      rather than in the corpocentric, agent-centred and often sport dominated
      strategies favoured by local policy makers. Our results support those who argue
      that interventions to increase rates of PA need to move beyond behavioural
      approaches that focus on individuals and consider the social, political and
      material contexts in which 'activity' occurs. 

PMID- 24911511
TI  - Intra-professional dynamics in translational health research: the perspective of
      social scientists.
AB  - In contrast to previous studies, which focus upon the professional dynamics of
      translational health research between clinician scientists and social scientists
      (inter-professional contestation), we focus upon contestation within social
      science (intra-professional contestation). Drawing on the empirical context of
      Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) in
      England, we highlight that although social scientists accept subordination to
      clinician scientists, health services researchers attempt to enhance their
      position in translational health research vis-a-vis organisation scientists, whom
      they perceive as relative newcomers to the research domain. Health services
      researchers do so through privileging the practical impact of their research,
      compared to organisation scientists' orientation towards development of theory,
      which health services researchers argue is decoupled from any concern with
      healthcare improvement. The concern of health services researchers lies with
      maintaining existing patterns of resource allocation to support their research
      endeavours, working alongside clinician scientists, in translational health
      research. The response of organisation scientists is one that might be considered
      ambivalent, since, unlike health services researchers, they do not rely upon a
      close relationship with clinician scientists to carry out research, or more
      generally, garner resource. 

PMID- 24911513
TI  - Preventing surgical site infection: preoperative bathing, why is it so important?

PMID- 24911512
TI  - Costs and consequences of a cash transfer for hospital births in a rural district
      of Uttar Pradesh, India.
AB  - The Janani Suraksha Yojana, India's "safe motherhood program," is a conditional
      cash transfer to encourage women to give birth in health facilities. Despite the
      program's apparent success in increasing facility-based births, quantitative
      evaluations have not found corresponding improvements in health outcomes. This
      study analyses original qualitative data collected between January, 2012 and
      November, 2013 in a rural district in Uttar Pradesh to address the question of
      why the program has not improved health outcomes. It finds that health service
      providers are focused on capturing economic rents associated with the program,
      and provide an extremely poor quality care. Further, the program does not
      ultimately provide beneficiaries a large net monetary transfer at the time of
      birth. Based on a detailed accounting of the monetary costs of hospital and home
      deliveries, this study finds that the value of the transfer to beneficiaries is
      small due to costs associated with hospital births. Finally, this study also
      documents important emotional and psychological costs to women of delivering in
      the hospital. These findings suggest the need for a substantial rethinking of the
      program, paying careful attention to incentivizing health outcomes. 

PMID- 24911514
TI  - Preventing surgical site infection: preoperative bathing, engaging patients and
      caregivers.

PMID- 24911515
TI  - The impact of the lateral geniculate nucleus and corticogeniculate interactions
      on efficient coding and higher-order visual object processing.
AB  - Principles of efficient coding suggest that the peripheral units of any sensory
      processing system are designed for efficient coding. The function of the lateral
      geniculate nucleus (LGN) as an early stage in the visual system is not well
      understood. Some findings indicate that similar to the retina that decorrelates
      input signals spatially, the LGN tends to perform a temporal decorrelation. There
      is evidence suggesting that corticogeniculate connections may account for this
      decorrelation in the LGN. In this study, we propose a computational model based
      on biological evidence reported by Wang et al. (2006), who demonstrated that the
      influence pattern of V1 feedback is phase-reversed. The output of our model shows
      how corticogeniculate connections decorrelate LGN responses and make an efficient
      representation. We evaluated our model using criteria that have previously been
      tested on LGN neurons through cell recording experiments, including sparseness,
      entropy, power spectra, and information transfer. We also considered the role of
      the LGN in higher-order visual object processing, comparing the categorization
      performance of human subjects with a cortical object recognition model in the
      presence and absence of our LGN input-stage model. Our results show that the new
      model that considers the role of the LGN, more closely follows the categorization
      performance of human subjects. 

PMID- 24911516
TI  - Quantitative monitoring of the Chlamydia trachomatis developmental cycle using
      GFP-expressing bacteria, microscopy and flow cytometry.
AB  - Chlamydiae are obligate intracellular bacteria. These pathogens develop inside
      host cells through a biphasic cycle alternating between two morphologically
      distinct forms, the infectious elementary body and the replicative reticulate
      body. Recently, C. trachomatis strains stably expressing fluorescent proteins
      were obtained. The fluorochromes are expressed during the intracellular growth of
      the microbe, allowing bacterial visualization by fluorescence microscopy. Whether
      they are also present in the infectious form, the elementary body, to a
      detectable level has not been studied. Here, we show that a C. trachomatis strain
      transformed with a plasmid expressing the green fluorescent protein (GFP)
      accumulates sufficient quantities of the probe in elementary bodies for detection
      by microscopy and flow cytometry. Adhesion of single bacteria was detected. The
      precise kinetics of bacterial entry were determined by microscopy using automated
      procedures. We show that during the intracellular replication phase, GFP is a
      convenient read-out for bacterial growth with several advantages over current
      methods. In particular, infection rates within a non-homogenous cell population
      are easily quantified. Finally, in spite of their small size, individual
      elementary bodies are detected by flow cytometers, allowing for direct
      enumeration of a bacterial preparation. In conclusion, GFP-expressing chlamydiae
      are suitable to monitor, in a quantitative manner, progression throughout the
      developmental cycle. This will facilitate the identification of the developmental
      steps targeted by anti-chlamydial drugs or host factors. 

PMID- 24911517
TI  - Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.
AB  - Edaravone, a potent antioxidant, may improve thrombolytic therapy because it
      benefits ischemic stroke patients on its own and mitigates adverse effects of
      tissue plasminogen activator (tPA) in preclinical models. However, whether the
      combined tPA-edaravone therapy is more effective in reducing infarct size than
      singular treatment is uncertain. Here we investigated this issue using a
      transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult
      C57BL/6 mice were subjected to reversible ligation of the unilateral common
      carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral
      occlusion of the common carotid artery suppressed cerebral blood flow
      transiently, the addition of hypoxia triggered reperfusion deficits, endogenous
      thrombosis, and attenuated tPA activity, leading up to infarction. We compared
      the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1,
      or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and
      infarct size as the primary end-points. The best treatment was further compared
      with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging
      (DTI) analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h
      post-tHI--significantly decreased infarct size and showed synergistic (p<0.05) or
      additive benefits with the adjuvant edaravone treatment, respectively. The acute
      tPA-edaravone treatment conferred >50% reduction of mortality, ~ 80% decline in
      infarct size, and strong white-matter protection. It also improved vascular
      reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix
      metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA
      treatment in experimental thrombotic stroke, suggesting that clinical application
      of the combined tPA-edaravone therapy merits investigation.

PMID- 24911518
TI  - HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through
      conduits and enhances HCV replication.
AB  - HIV-1 infection enhances HCV replication and as a consequence accelerates HCV
      mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism
      by which this takes place is currently unknown. Our data showed that infectious
      HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus
      replication was observed, even when the cell lines transfected with HIV-1
      proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of
      liver deterioration in the co-infected patient is not due to the replication of
      HIV-1 in the hepatocytes of the HCV infected host. Instead, HIV-1 Nef protein was
      transferred from nef-expressing T cells to hepatocytic cells through conduits,
      wherein up to 16% (average 10%) of the cells harbored the transferred Nef, when
      the hepatocytic cells were co-cultured with nef-expressing Jurkat cells for 24 h.
      Further, Nef altered the size and numbers of lipid droplets (LD), and
      consistently up-regulated HCV replication by 1.5~2.5 fold in the target
      subgenomic replicon cells, which is remarkable in relation to the initially
      indolent viral replication. Nef also dramatically augmented reactive oxygen
      species (ROS) production and enhanced ethanol-mediated up-regulation of HCV
      replication so as to accelerate HCC. Taken together, these data indicate that HIV
      1 Nef is a critical element in accelerating progression of liver pathogenesis via
      enhancing HCV replication and coordinating modulation of key intra- and extra
      cellular molecules for liver decay. 

PMID- 24911519
TI  - High anti-viral protection without immune upregulation after interspecies
      Wolbachia transfer.
AB  - Wolbachia, endosymbionts that reside naturally in up to 40-70% of all insect
      species, are some of the most prevalent intracellular bacteria. Both Wolbachia
      wAu, naturally associated with Drosophila simulans, and wMel, native to
      Drosophila melanogaster, have been previously described to protect their hosts
      against viral infections. wMel transferred to D. simulans was also shown to have
      a strong antiviral effect. Here we directly compare one of the most protective
      wMel variants and wAu in D. melanogaster in the same host genetic background. We
      conclude that wAu protects better against viral infections, it grows
      exponentially and significantly shortens the lifespan of D. melanogaster.
      However, there is no difference between wMel and wAu in the expression of
      selected antimicrobial peptides. Therefore, neither the difference in anti-viral
      effect nor the life-shortening could be attributed to the immune stimulation by
      exogenous Wolbachia. Overall, we prove that stable transinfection with a highly
      protective Wolbachia is not necessarily associated with general immune
      activation. 

PMID- 24911521
TI  - Perinatal outcomes of borderline diabetic pregnant women.
AB  - We examined the perinatal outcomes of borderline diabetic pregnant women who had
      impaired 50 g oral glucose challenge test (OGCT) results, but normal 100 g oral
      glucose tolerance test (OGTT) results. Our study group included 70 pregnant women
      who had increased 50 g OGCT results, but normal 100 g OGTT results, and a control
      group of 122 pregnant women with normal 50 g OGCT results. Polyhydramnios,
      macrosomia and neonatal birth weight were significantly higher in the study
      group. After adjusting the results for possibly affecting variables, the risk of
      polyhydramnios remained significant, while the risk of macrosomia and neonatal
      birth weight was not significant between the groups. The results from the study
      group were similar to the control group, when adjusted for other risk factors.
      Increased 50 g OGCT results in pregnant women can be accepted as a benign state
      if the 100 g OGTT results are normal.

PMID- 24911520
TI  - Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal
      stem cells via macrophage polarisation state.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) are a promising cell type for the repair
      of damaged cartilage in osteoarthritis (OA). However, OA synovial fluid and
      factors secreted by synovium impede chondrogenic differentiation of MSCs, and the
      mechanism responsible for this effect remains unclear. In this study, we sought
      to investigate whether M1 and M2 synovial macrophages can contribute to the
      inhibition of MSC chondrogenesis. DESIGN: The constitution of synovial macrophage
      subsets was analysed by immunohistochemical staining of human OA synovium
      sections for CD86 (M1 marker) and CD206 (M2 marker). To assess the effect of
      synovial macrophages on chondrogenesis, collagen type II (COL2) and aggrecan
      (ACAN) gene expression were compared between MSCs undergoing chondrogenic
      differentiation in medium conditioned (CM) by human OA synovial explants, human
      synovial macrophages and fibroblasts, or peripheral blood derived primary human
      monocytes differentiated towards an M1 or M2 phenotype. RESULTS: OA synovium
      contained both M1 and M2 macrophages. Medium conditioned by synovial macrophages
      (CD45 + plastic adherent cells) down-regulated chondrogenic gene expression by
      MSCs. Additionally, CM of M1 polarised monocytes significantly decreased COL2 and
      ACAN gene expression by MSCs; this effect was not observed for treatment with CM
      of M2 polarised monocytes. CONCLUSION: MSC chondrogenesis is inhibited by OA
      synovium CM through factors secreted by synovial macrophages and our findings
      suggest that M1 polarised subsets are potential mediators of this anti
      chondrogenic effect. Modulation of macrophage phenotype may serve as a beneficial
      strategy to maximise the potential of MSCs for efficient cartilage repair.

PMID- 24911523
TI  - Omega-3 free fatty acids suppress macrophage inflammasome activation by
      inhibiting NF-kappaB activation and enhancing autophagy.
AB  - The omega-3 (omega3) fatty acid docosahexaenoic acid (DHA) can suppress
      inflammation, specifically IL-1beta production through poorly understood
      molecular mechanisms. Here, we show that DHA reduces macrophage IL-1beta
      production by limiting inflammasome activation. Exposure to DHA reduced IL-1beta
      production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4
      inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR) 4 (also
      known as GPR120), a G-protein coupled receptor (GPR) known to bind DHA. The
      exposure of cells to DHA recruited the adapter protein beta-arrestin1/2 to FFAR4,
      but not to a related lipid receptor. DHA treatment reduced the initial
      inflammasome priming step by suppressing the nuclear translocation of NF-kappaB.
      DHA also reduced IL-1beta levels by enhancing autophagy in the cells. As a
      consequence macrophages derived from mice lacking the essential autophagy protein
      ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses
      inflammasome activation by two distinct mechanisms, inhibiting the initial
      priming step and by augmenting autophagy, which limits inflammasome activity. 

PMID- 24911524
TI  - Screening, assessment, and treatment of osteoporosis for the nurse practitioner:
      key questions and answers for clinical practice--a Canadian perspective.
AB  - PURPOSE: Using a case-based approach, we review key clinical questions relevant
      to nurse practitioners (NPs) regarding the screening, assessment, and treatment
      of patients at risk for osteoporosis and fractures in a Canadian general practice
      setting. DATA SOURCES: A case presentation with relevant questions and answers to
      guide management of a patient. CONCLUSIONS: Osteoporosis is a common condition in
      both the aging male and female populations. Screening, diagnosis, and treatment
      of osteoporosis is lagging behind relative to other chronic disease states. NPs
      have a unique opportunity to help reduce this care gap by playing an integral
      role in the identification, risk stratification, and treatment of patients at
      risk for osteoporosis and fractures. IMPLICATIONS FOR PRACTICE: This case
      highlights the important role an NP can have in screening a patient previously
      not diagnosed or managed for osteoporosis. Performing a focused history and
      physical exam of the patient to determine appropriate screening tests and
      fracture risk will help in guiding treatment decisions.

PMID- 24911522
TI  - Unchanged plasma levels of the soluble urokinase plasminogen activator receptor
      in elective coronary artery bypass graft surgery patients and cardiopulmonary
      bypass use.
AB  - OBJECTIVE AND DESIGN: The soluble urokinase plasminogen activator receptor
      (suPAR) has been recently recognized as a potential biological marker of various
      disease states, but the impact of a major surgical intervention on the suPAR
      level has not yet been established. The aim of our study was to investigate if
      the induction of a systemic inflammatory reaction in response to cardiopulmonary
      bypass would be accompanied by an increase in the plasma suPAR level. METHODS AND
      SUBJECTS: Patients undergoing coronary artery bypass grafting under
      cardiopulmonary bypass (CPB) were added. Based on the baseline suPAR level,
      patients were divided into group 1 (suPAR within normal range) or group 2 (suPAR
      above range). Blood was collected before the induction of anesthesia and 6 and 24
      hours after surgery. Plasma suPAR, IL-6, IL-8, TNF-alpha, troponin I, NT-proBNP,
      and NGAL were quantified to assess the impact of surgical trauma on these
      markers. RESULTS: The baseline suPAR level was within the normal range in 31
      patients (3.3 ng/mL), and elevated in 29 (5.1 ng/mL) (p<0.001). Baseline
      mediators of systemic inflammatory reaction concentrations (IL-6, TNF-alpha, and
      IL-8) and organ injury indices (troponin I, NT-proBNP, and NGAL) were low and
      increased after surgery in all patients (p<0.05). The surgery did not cause
      significant changes in the suPAR level either at 6 or 24 hours after, however the
      difference between groups observed at baseline remained substantial during the
      postoperative period. CONCLUSIONS: There was no change in the suPAR level
      observed in patients subjected to elective cardiac coronary artery bypass surgery
      and CPB, despite activation of a systemic inflammatory reaction.

PMID- 24911526
TI  - Understanding the rates and molecular mechanism of water-exchange around aqueous
      ions using molecular simulations.
AB  - Solvation processes occurring around aqueous ions are of fundamental importance
      in physics, chemistry, and biology. Over the past few decades, several
      experimental and theoretical studies were devoted to understanding ion solvation
      and the processes involved in it. In this article, we present a summary of our
      recent efforts that, through computer simulations, focused on providing a
      comprehensive understanding of solvent-exchange processes around aqueous ions. To
      accomplish these activities, we have looked at the mechanistic properties
      associated with the water-exchange process, such as potentials of mean force,
      time-dependent transmission coefficients, and the corresponding rate constants
      using transition state theory, the reactive flux method, and Grote-Hynes
      treatments of the dynamic response of the solvent. 

PMID- 24911525
TI  - Complex IV-deficient Surf1(-/-) mice initiate mitochondrial stress responses.
AB  - Mutations in SURF1 (surfeit locus protein 1) COX (cytochrome c oxidase) assembly
      protein are associated with Leigh's syndrome, a human mitochondrial disorder that
      manifests as severe mitochondrial phenotypes and early lethality. In contrast,
      mice lacking the SURF1 protein (Surf1-/-) are viable and were previously shown to
      have enhanced longevity and a greater than 50% reduction in COX activity. We
      measured mitochondrial function in heart and skeletal muscle, and despite the
      significant reduction in COX activity, we found little or no difference in ROS
      (reactive oxygen species) generation, membrane potential, ATP production or
      respiration in isolated mitochondria from Surf1-/- mice compared with wild-type.
      However, blood lactate levels were elevated and Surf1-/- mice had reduced running
      endurance, suggesting compromised mitochondrial energy metabolism in vivo.
      Decreased COX activity in Surf1-/- mice is associated with increased markers of
      mitochondrial biogenesis [PGC-1alpha (peroxisome-proliferator-activated receptor
      gamma co-activator 1alpha) and VDAC (voltage-dependent anion channel)] in both
      heart and skeletal muscle. Although mitochondrial biogenesis is a common response
      in the two tissues, skeletal muscle has an up-regulation of the UPRMT
      (mitochondrial unfolded protein response) and heart exhibits induction of the
      Nrf2 (nuclear factor-erythroid 2-related factor 2) antioxidant response pathway.
      These data are the first to show induction of the UPRMT in a mammalian model of
      decreased COX activity. In addition, the results of the present study suggest
      that impaired mitochondrial function can lead to induction of mitochondrial
      stress pathways to confer protective effects on cellular homoeostasis. 

PMID- 24911527
TI  - Multistage screening reveals chameleon ligands of the human farnesyl
      pyrophosphate synthase: implications to drug discovery for neurodegenerative
      diseases.
AB  - Human farnesyl pyrophosphate synthase (hFPPS) is the gate-keeper of mammalian
      isoprenoids and the key target of bisphosphonate drugs. Bisphosphonates suffer
      from poor "drug-like" properties and are mainly effective in treating skeletal
      diseases. Recent investigations have implicated hFPPS in various nonskeletal
      diseases, including Alzheimer's disease (AD). Analysis of single nucleotide
      polymorphisms in the hFPPS gene and mRNA levels in autopsy-confirmed AD subjects
      was undertaken, and a genetic link between hFPPS and phosphorylated tau (P-Tau)
      levels in the human brain was identified. Elevated P-Tau levels are strongly
      implicated in AD progression. The development of nonbisphosphonate inhibitors can
      provide molecular tools for validating hFPPS as a therapeutic target for
      tauopathy-associated neurodegeneration. A multistage screening protocol led to
      the identification of a new monophosphonate chemotype that bind in an allosteric
      pocket of hFPPS. Optimization of these compounds could lead to human therapeutics
      that block tau metabolism and arrest the progression of neurodegeneration.

PMID- 24911528
TI  - Spine injury following a low-energy trauma in ankylosing spondylitis: a study of
      two cases.
AB  - We report two cases of spine injury following a low-energy trauma in persons with
      ankylosing spondylitis (AS) and discuss the forensic considerations. A 60-year
      old man presented with a wide anterior fracture of the superior endplate of T8
      after an accidental fall down three wooden steps. A 93-year-old man presented
      with disjunction between C6 and C7 and 90-degree spinal angulation after a fall
      from a standing height or a fall from a bed. Post-mortem multislice computed
      tomography (MSCT) was performed before autopsy in both the cases. MSCT and
      autopsy findings were in agreement with a past medical history of AS. A spine
      injury occurring after a low-energy trauma is unusual and could be suspicious. In
      the forensic literature we found only a single case, which concerned multiple
      spinal fractures after a fall from a bicycle at low speed. Such specific
      mechanisms must be studied and known to the forensic expert. In this context,
      MSCT is a useful tool to investigate the spine and knowledge of the victim's
      entire past medical history is essential. 

PMID- 24911529
TI  - Injectable poly(oligoethylene glycol methacrylate)-based hydrogels with tunable
      phase transition behaviours: physicochemical and biological responses.
AB  - The potential of poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels with
      varying thermosensitivities as soft materials for biomedical applications is
      demonstrated. Hydrogels are prepared from hydrazide and aldehyde functionalized
      POEGMA precursors, yielding POEGMA hydrogels with a volume phase transition
      temperature (VPTT) below (PO0), close to (PO10) and well above (PO100)
      physiological temperature. Hydrogels with VPTTs close to and above physiological
      temperature exhibit biological properties similar to those typically observed for
      poly(ethylene glycol) hydrogels (i.e. low protein adsorption, low cell adhesion
      and minimal inflammatory responses in vivo) while hydrogels with VPTTs lower than
      physiological temperature exhibit biological properties more analogous to poly(N
      isopropylacrylamide) above its phase transition temperature (temperature
      switchable cell adhesion, higher protein adsorption and somewhat more acute
      inflammation in vivo). As such, the use of POEGMA precursors with varying chain
      lengths of ethylene oxide grafts offers a versatile platform for the design of
      hydrogels with tunable physiological properties via simple copolymerization. 

PMID- 24911531
TI  - Tailoring the interface quality between HfO2 and GaAs via in situ ZnO passivation
      using atomic layer deposition.
AB  - We investigated ZnO surface passivation of a GaAs (100) substrate using an atomic
      layer deposition (ALD) process to prepare an ultrathin ZnO layer prior to ALD
      HfO2 gate dielectric deposition. Significant suppression of both Ga-O bond
      formation near the interface and As segregation at the interface was achieved. In
      addition, this method effectively suppressed the trapping of carriers in oxide
      defects with energies near the valence band edge of GaAs. According to electrical
      analyses of the interface state response on p- and n-type GaAs substrates, the
      interface states in the bottom half of the GaAs band gap were largely removed.
      However, the interface trap response in the top half of the band gap increased
      somewhat for the ZnO-passivated surface. 

PMID- 24911530
TI  - Bovine and equine peritubular and intertubular dentin.
AB  - Dentin contains 1-2MUm diameter tubules extending from the pulp cavity to near
      the junction with enamel. Peritubular dentin (PTD) borders the tubule lumens and
      is surrounded by intertubular dentin (ITD). Differences in PTD and ITD
      composition and microstructure remain poorly understood. Here, a (~200nm)(2),
      10.1keV synchrotron X-ray beam maps X-ray fluorescence and X-ray diffraction
      simultaneously around tubules in 15-30MUm thick bovine and equine specimens.
      Increased Ca fluorescence surrounding tubule lumens confirms that PTD is present,
      and the relative intensities in PTD and ITD correspond to carbonated apatite
      (cAp) volume fraction of ~0.8 in PTD vs. 0.65 assumed for ITD. In the PTD near
      the lumen edges, Zn intensity is strongly peaked, corresponding to a Zn content
      of ~0.9mgg(-1) for an assumed concentration of ~0.4mgg(-1) for ITD. In the equine
      specimen, the Zn K-edge position indicates that Zn(2+) is present, similar to
      bovine dentin (Deymier-Black et al., 2013), and the above edge structure is
      consistent with spectra from macromolecules related to biomineralization.
      Transmission X-ray diffraction shows only cAp, and the 00.2 diffraction peak
      (Miller-Bravais indices) width is constant from ITD to the lumen edge. The cAp
      00.2 average preferred orientation is axisymmetric (about the tubule axis) in
      both bovine and equine dentin, and the axisymmetric preferred orientation
      continues from ITD through the PTD to the tubule lumen. These data indicate that
      cAp structure does not vary from PTD to ITD. 

PMID- 24911532
TI  - Re-examining the role of context in implicit sequence learning.
AB  - Implicit sequence learning typically develops gradually, is often expressed quite
      rigidly, and is heavily reliant on contextual features. Recently we reported
      results pointing to the role of context-specific processes in the acquisition and
      expression of implicit sequence knowledge (D'Angelo, Milliken, Jimenez, &
      Lupianez, 2013). Here we examined further the role of context in learning of
      first-order conditional sequences, and whether context also plays a role in
      learning second-order conditional structures. Across five experiments we show
      that the role of context in first-order conditional sequences may not be as clear
      as we had previously reported, while at the same time we find evidence for the
      role of context in learning second-order conditional sequences. Together the
      results suggest that temporal context may be sufficient to learn complementary
      first-order conditional sequences, but that additional contextual information is
      necessary to concurrently learn higher-order sequential structures. 

PMID- 24911533
TI  - Caruncular fixation in medial canthal tendon repair: the minimally invasive purse
      string suture for tendinous laxity and medial ectropion.
AB  - PURPOSE: To describe a surgical technique for repair of medial ectropion that
      simply and reliably addresses tendinous laxity and punctal eversion. METHODS:
      Prospective, single-blind, consecutive case study of 54 patients (79 eyes) by 3
      surgeons. The subject population consisted of 33 males and 21 females, with a
      mean age of 81 years (SD = 9, range = 64-97). The presenting mechanisms of
      ectropion were as follows: cicatricial (n = 10), paralytic (n = 1), involutional
      (n = 62), mechanical (n = 3), and congenital (n = 3). Ectropion and punctal
      eversion was surgically addressed by use of a purse string suture that
      incorporated closure of a medial spindle incision and deep fixation to the base
      of the caruncle. RESULTS: The average postoperative follow-up period was 147 days
      (SD = 291, range 8-2,352). Sixty-four eyes had a presenting complaint of tearing
      (81%), with 50 eyes (78%) achieving complete resolution (p = 0.0001). Eyelid
      malposition was determined to be anatomically corrected in 34 of 35 eyes (97%, p
      = 0.0001). Four of the 79 operated eyelids had recurrence of ectropion (5%). All
      other reported complications were minor, resolved without sequalae. CONCLUSION:
      The technique demonstrated safety, efficacy, and reproducibility, regardless of
      ectropion mechanism. Incorporation of a purse string suture between the lower
      eyelid portion of the medial canthal tendon and the caruncle produces a reliable
      posterior-superior fixation parallel to the vectors of the posterior limb of the
      medial canthal tendon. This technique is equally effective as a primary
      correction method or when used in combination with other procedures.

PMID- 24911534
TI  - The clinical characterization and surgical correction of blepharoptosis
      associated with congenital aniridia.
AB  - PURPOSE: To document the clinical characteristics and describe our management of
      patients with blepharoptosis associated with congenital aniridia. METHODS:
      Consecutive retrospective case series of patients with congenital aniridia seen
      at a single institution (Cincinnati Eye Institute) from 1963 to 2010. Surgical
      correction was performed by 2 surgeons (J.A.N. and R.C.K.). RESULTS: Ptosis
      associated with congenital aniridia is marked with decreased levator function.
      Significant comorbid ophthalmologic disease was invariably present, particularly
      aniridia-associated keratopathy. Complications, most often keratopathy, were
      common, even following conservative correction. CONCLUSIONS: The degree of ptosis
      is significant, and levator function is typically reduced. Ocular surface
      viability appears to play a key role in preoperative, intraoperative, and
      postoperative management. While we are aware that congenital aniridia is rather
      rare, we believe these recommendations are generalizable to patients with severe
      ocular surface disease.

PMID- 24911535
TI  - Ocular surface, fornix, and eyelid rehabilitation in Boston type I
      keratoprosthesis patients with mucous membrane disease.
AB  - PURPOSE: To understand the efficacy of various approaches for ocular surface
      reconstruction in eyes with implanted Boston Type I keratoprosthesis. METHODS:
      All eyes implanted with a Boston Type I keratoprosthesis over a 9-year period by
      a single surgeon were reviewed. Any case in which mucosal rehabilitation was
      performed was included in the study sample. The type, number, approach, and
      outcome for all eyelid and ocular surface procedures were assessed. RESULTS: A
      total of 22 mucosal surface surgeries were performed before, concurrent with, and
      after implantation of 11 keratoprostheses and 1 penetrating keratoplasty (after
      keratoprosthesis removal) in 9 eyes of 9 patients. Most of the ocular surface
      reconstructive surgeries (81.8%; 18/22) were performed at the time of or
      following keratoprosthesis implantation, with the most common indication being
      corneal stromal necrosis (44.4%; 8/18). Free grafting and simple advancement
      resulted in graft retraction for each case, and pedicle or bucket handle flaps
      resulted in a stable vascularized graft for half of the cases. Graft retraction
      occurred in 6 of the 9 eyes in this study, including in all 5 eyes of patients
      with Stevens Johnsons syndrome (SJS). CONCLUSIONS: Free grafting and simple
      advancement flaps do not appear to be effective for rehabilitation in these eyes.
      However, even vascularized pedicle and bucket handle flaps retracted 50% of the
      time. Individuals with SJS were more likely to both require conjunctival
      rehabilitation after keratoprosthesis surgery and develop graft retraction in the
      course of management.

PMID- 24911536
TI  - Pemetrexed-Associated Eyelid Edema: Effective Treatment by Excision of
      Lymphedematous Eyelid Tissue.
AB  - Pemetrexed is an antimetabolite agent that inhibits multiple folate-requiring
      enzymes and is used in the treatment of mesothelioma and non-small-cell lung
      cancer. One of its toxicities is isolated cutaneous swelling affecting the
      eyelids and/or orbit. The pathologic assessment or its management has not been
      addressed to date. Herein, the authors report a case of a 77-year-old woman
      treated with pemetrexed for non-small-cell lung adenocarcinoma who developed
      persistent, severe bilateral lower eyelid swelling for several months, despite
      compresses and oral diphenhydramine. Elective excision was performed with good
      results and no recurrence after 6 months' follow up. Histopathologically, the
      excised tissue showed changes typical of dermatochalasis with dissolution of
      collagen and elastic bundles and marked dilation of lymphatic vessels. The
      combination of pre-existing, localized lymphatic failure and capillary leakage
      secondary to pemetrexed therapy can explain the onset and worsening swelling with
      successive rounds of chemotherapy. 

PMID- 24911537
TI  - Cerebrospinal Fluid Leak Presenting as Epiphora.
AB  - A 52-year-old woman underwent a right frontotemporal craniotomy for microsurgical
      clip obliteration of a ruptured right dorsal variant ophthalmic segment carotid
      aneurysm. During the craniotomy, a defect involving the orbital roof was
      inadvertently created. The patient was noted postoperatively to have fluid
      egressing from her OD. The fluid was analyzed and based on glucose and chloride
      levels was determined to be cerebrospinal fluid (CSF). CT scan of the head
      demonstrated the orbital roof defect created during surgery. After placement of a
      lumbar drain, fluid egress from the eye significantly decreased, further
      confirming the suspicion for CSF leak. Patient was found to have a conjunctival
      defect of the OD, approximately 2.5 cm * 1.5 cm, extending to the fornix from 9
      to 12 o'clock. The conjunctival defect and fornix were repaired with an amniotic
      membrane graft and a temporary tarsorrhaphy with subsequent resolution of CSF
      egress. The case report is in compliance with the Health Insurance Portability
      and Accountability Act.

PMID- 24911538
TI  - Spindle Cell Lipoma of the Conjunctiva.
AB  - A 67-year-old woman presented with progressive enlargement of a long-standing
      mass on the surface of her OS associated with ocular surface irritation. The mass
      was excised en bloc. Histopathological examination showed a well-defined
      encapsulated tumor composed of wiry collagen containing bland spindle cells that
      were strongly positive for CD34 with scattered mature adipocytes. These features
      confirmed a diagnosis of spindle cell lipoma.

PMID- 24911539
TI  - Pseudoadenomatous Hyperplasia of the Inferior Forniceal Conjunctiva Due To
      Prosthetic Irritation in an Anophthalmic Socket.
AB  - Secondary complications in an anophthalmic socket can include late appearing
      shrinkage due to scarring and squamous cell carcinoma. This article reports a 51
      year-old man who 27 years after an enucleation developed an inability to retain
      his ocular prosthesis due to an acquired multilobular fleshy mass in his inferior
      fornix. The patient had worn his prosthesis without removal for years at a time.
      Microscopic evaluation of the excised lesion disclosed a pseudoadenomatous
      (pseudoglandular) hyperplasia of the conjunctival epithelium with myriad goblet
      cells and accompanying chronic inflammation. In cross section, these structures
      microscopically resembled an adenoma but were found to display multifocal origins
      from the surface epithelium resembling exaggerated pseudoglands of Henle. Simple
      excision without recurrence 6 months later has permitted a new prosthesis to be
      comfortably worn with stability.

PMID- 24911540
TI  - Adolescents living with a parent with advanced cancer: a review of the
      literature.
AB  - OBJECTIVE: Families and children facing the death of a parent from cancer
      constitute a vulnerable population often overlooked by healthcare professionals
      and researchers. The purpose of this review is to provide a systematic analysis
      of the literature that examines the experiences of parents diagnosed with
      advanced cancer and their adolescent children. METHODS: Reviews of quantitative,
      qualitative, and mixed method publications between 2000 and 2013 were selected in
      order to obtain the most current and timely studies. Articles published before
      2000 but found to be seminal works on this topic were also included. No time
      limits were set on intervention studies. RESULTS: Eighteen studies met the
      criteria for the content of this review, indicating the limited number of studies
      conducted on this topic. Articles were summarized using the following categories:
      original research on the impact on the family and parenting, original research on
      the impact on the child/adolescent, and interventions for families facing
      incurable cancer. The analysis was organized around the major themes found in the
      literature within each category. CONCLUSIONS: These themes will allow healthcare
      professionals to understand implications for clinical practice and apply the
      knowledge gained from this analysis of literature to guide future research.

PMID- 24911541
TI  - Quality-of-life in patients with post-traumatic hypopituitarism.
AB  - PRIMARY OBJECTIVE: Hypopituitarism is a frequent complication in patients after
      traumatic brain injury (TBI). Both TBI and hypopituitarism can lead to complex
      cognitive and affective deficits. This study was intended to examine the quality
      of-life in patients with post-traumatic hypopituitarism (PTH) and to discern the
      effect of this endocrinological disorder on general outcome of patients after TBI
      including earning capacity. Research type: Retrospective analysis of clinical
      data. METHODS AND PROCEDURES: Ninety-seven symptomatic patients were screened
      after TBI for PTH. Their results were examined in the SF-36 [a standardized
      questionnaire for quality of life (QoL)] comparing the groups with or without
      PTH. After 6 months of hormone substitution (if necessary), patients were asked
      to repeat the SF-36. MAIN OUTCOMES AND RESULTS: Forty-six patients were diagnosed
      with PTH (47.5%). All patients included had a significantly lower QoL compared to
      the standard population. QoL was significantly worse in patients with PTH. There
      was no significant difference with regard to earning capacity. After hormone
      substitution, patients achieved better SF-36-results, albeit the difference was
      lacking statistical significance. CONCLUSIONS: PTH is frequent after TBI. PTH
      turns out to further diminish QoL, without affecting earning capacity. Hormone
      substitution might improve QoL in patients with PTH, but future research is
      needed to confirm this hypothesis.

PMID- 24911542
TI  - Thunberol, a new sterol from the Chinese brown alga Sargassum thunbergii.
AB  - A new sterol, named thunberol (1), along with four known analogs, 24
      ethylcholesta-4,24(28)-dien-3-one (2), stigmasta-5,28-dien-3beta-ol (3), cholesta
      5,14-dien-3beta-ol (4), and cholesta-5,23-dien-3beta,25-diol (5), were isolated
      from the brown alga Sargassum thunbergii collected from East China Sea. The
      structures of these metabolites were elucidated on the basis of detailed
      spectroscopic analysis and by comparison with the literature data. Thunberol (1)
      exhibited significant inhibitory activity against protein tyrosine phosphatase
      1B, a potential drug target for the treatment of Type-II diabetes and obesity,
      with an IC50 value of 2.24 MUg/ml.

PMID- 24911543
TI  - Nanoconfined beta-sheets mechanically reinforce the supra-biomolecular network of
      robust squid Sucker Ring Teeth.
AB  - The predatory efficiency of squid and cuttlefish (superorder Decapodiformes) is
      enhanced by robust Sucker Ring Teeth (SRT) that perform grappling functions
      during prey capture. Here, we show that SRT are composed entirely of related
      structural "suckerin" proteins whose modular designs enable the formation of
      nanoconfined beta-sheet-reinforced polymer networks. Thirty-seven previously
      undiscovered suckerins were identified from transcriptomes assembled from three
      distantly related decapodiform cephalopods. Similarity in modular sequence design
      and exon-intron architecture suggests that suckerins are encoded by a multigene
      family. Phylogenetic analysis supports this view, revealing that suckerin genes
      originated in a common ancestor ~350 MYa and indicating that nanoconfined beta
      sheet reinforcement is an ancient strategy to create robust bulk biomaterials. X
      ray diffraction, nanomechanical, and micro-Raman spectroscopy measurements
      confirm that the modular design of the suckerins facilitates the formation of
      beta-sheets of precise nanoscale dimensions and enables their assembly into
      structurally robust supramolecular networks stabilized by cooperative hydrogen
      bonding. The suckerin gene family has likely played a key role in the
      evolutionary success of decapodiform cephalopods and provides a large molecular
      toolbox for biomimetic materials engineering.

PMID- 24911544
TI  - Influence of clay particles on the transport and retention of titanium dioxide
      nanoparticles in quartz sand.
AB  - This study investigated the influence of two representative suspended clay
      particles, bentonite and kaolinite, on the transport of titanium dioxide
      nanoparticles (nTiO2) in saturated quartz sand in both NaCl (1 and 10 mM ionic
      strength) and CaCl2 solutions (0.1 and 1 mM ionic strength) at pH 7. The
      breakthrough curves of nTiO2 with bentonite or kaolinite were higher than those
      without the presence of clay particles in NaCl solutions, indicating that both
      types of clay particles increased nTiO2 transport in NaCl solutions. Moreover,
      the enhancement of nTiO2 transport was more significant when bentonite was
      present in nTiO2 suspensions relative to kaolinite. Similar to NaCl solutions, in
      CaCl2 solutions, the breakthrough curves of nTiO2 with bentonite were also higher
      than those without clay particles, while the breakthrough curves of nTiO2 with
      kaolinite were lower than those without clay particles. Clearly, in CaCl2
      solutions, the presence of bentonite in suspensions increased nTiO2 transport,
      whereas, kaolinite decreased nTiO2 transport in quartz sand. The attachment of
      nTiO2 onto clay particles (both bentonite and kaolinite) were observed under all
      experimental conditions. The increased transport of nTiO2 in most experimental
      conditions (except for kaolinite in CaCl2 solutions) was attributed mainly to the
      clay-facilitated nTiO2 transport. The straining of larger nTiO2-kaolinite
      clusters yet contributed to the decreased transport (enhanced retention) of nTiO2
      in divalent CaCl2 solutions when kaolinite particles were copresent in
      suspensions. 

PMID- 24911546
TI  - Simultaneous determination of five novel luteinizing hormone-releasing hormone
      antagonists by LC-MS and pharmacokinetics in rats following cassette dosing.
AB  - Long acting luteinizing hormone-releasing hormone (LHRH) antagonists designed to
      be protease-resistant were a series of novel decapeptides structurally similar to
      LHRH. In the present work, a high-throughput method based on a LC-MS/MS has been
      developed for the simultaneous determination of pharmacokinetics of five LHRH
      antagonists in rat via cassette dosing. The method was performed under selected
      reaction monitoring (SRM) in positive ion mode. The analytes were extracted from
      rat plasma by liquid-liquid extraction with acetonitrile. Chromatographic
      separation of the analytes was successfully achieved on a Hypersil Gold
      (100mm*2.1mm, 3MUm) using a mobile phase composed of acetonitrile-water (30:70)
      containing 0.05% (v/v) formic acid. The result showed good linearity and
      selectivity were obtained for all antagonists. The limits of quantification of
      the five LHRH antagonists were from 5 to 10ng/mL. The average extract recoveries
      in the rat plasma were all over 72%. The intra-day and inter-day precisions
      (R.S.D. %) were all within 10% and the accuracy was ranged from 92.54 to 109.05%.
      This method has been successfully applied to the pharmacokinetic studies of the
      five LHRH antagonists. The results indicated that the plasma drug concentrations
      versus time curves after intravenous injection of five antagonists via cassette
      dosing were all fitted to a two-compartment model. The pharmacokinetic parameters
      of five LHRH antagonists suggested that LY616 could be the more stable candidate
      drugs and optimized as the candidate drug for further study. Our studies enabled
      high-throughput rapid screening for pharmacokinetic assessment of new peptide
      candidates, and provided abundant information on the metabolic properties of
      these LHRH antagonists. 

PMID- 24911545
TI  - Molecular mechanisms of aldehyde toxicity: a chemical perspective.
AB  - Aldehydes are electrophilic compounds to which humans are pervasively exposed.
      Despite a significant health risk due to exposure, the mechanisms of aldehyde
      toxicity are poorly understood. This ambiguity is likely due to the structural
      diversity of aldehyde derivatives and corresponding differences in chemical
      reactions and biological targets. To gain mechanistic insight, we have used
      parameters based on the hard and soft, acids and bases (HSAB) theory to profile
      the different aldehyde subclasses with respect to electronic character (softness,
      hardness), electrophilic reactivity (electrophilic index), and biological
      nucleophilic targets. Our analyses indicate that short chain aldehydes and longer
      chain saturated alkanals are hard electrophiles that cause toxicity by forming
      adducts with hard biological nucleophiles, e.g., primary nitrogen groups on
      lysine residues. In contrast, alpha,beta-unsaturated carbonyl derivatives,
      alkenals, and the alpha-oxoaldehydes are soft electrophiles that preferentially
      react with soft nucleophilic thiolate groups on cysteine residues. The aldehydes
      can therefore be grouped into subclasses according to common electronic
      characteristics (softness/hardness) and molecular mechanisms of toxicity. As we
      will discuss, the toxic potencies of these subgroups are generally related to
      corresponding electrophilicities. For some aldehydes, however, predictions of
      toxicity based on electrophilicity are less accurate due to inherent
      physicochemical variables that limit target accessibility, e.g., steric hindrance
      and solubility. The unsaturated aldehydes are also members of the conjugated type
      2 alkene chemical class that includes alpha,beta-unsaturated amide, ketone, and
      ester derivatives. Type-2 alkenes are electrophiles of varying softness and
      electrophilicity that share a common mechanism of toxicity. Therefore, exposure
      to an environmental mixture of unsaturated carbonyl derivatives could cause "type
      2 alkene toxicity" through additive interactions. Finally, we propose that
      environmentally derived aldehydes can accelerate diseases by interacting with
      endogenous aldehydes generated during oxidative stress. This review provides a
      basis for understanding aldehyde mechanisms and environmental toxicity through
      the context of electronic structure, electrophilicity, and nucleophile target
      selectivity. 

PMID- 24911547
TI  - Analytical sample preparation strategies for the determination of antimalarial
      drugs in human whole blood, plasma and urine.
AB  - Antimalarial drugs commonly referred to as antimalarials, include a variety of
      compounds with different physicochemical properties. There is a lack of
      information on antimalarial distribution in the body over time after
      administration, e.g. the drug concentrations in whole blood, plasma, and urine,
      which must be improved in order to advance curing the parasitic disease malaria.
      A key problem also lies in that pharmacokinetic studies not always are performed
      in patient groups that may benefit most of the treatment such as children,
      pregnancy and lower-weight ethnic populations. Here we review the available
      sample preparation strategies combined with liquid chromatographic (LC) analysis
      to determine antimalarials in whole blood, plasma and urine published over the
      last decade. Sample preparation can be done by protein precipitation, solid-phase
      extraction, liquid-liquid extraction or dilution. After LC separation, the
      preferred detection tool is tandem mass spectrometry (MS/MS) but other detection
      methods have been used e.g. UV, fluorescence and electrochemical detection. Major
      trends for sample preparation of the different groups of antimalarials for each
      matrix and its detection have been summarized. Finally, the main problems that
      the researchers have dealt with are highlighted. This information will aid
      analytical chemists in the development of novel methods for determining existing
      antimalarials and upcoming new drugs. 

PMID- 24911548
TI  - Bio-distribution and pharmacokinetics of nobiliside A-loaded liposome following
      intravenous administration in rats.
AB  - Nobiliside A (Nob) is a new triterpenoid saponin separated from Holothuria
      noblilis. In this article, a liquid chromatography-electrospray ionization-tandem
      mass spectrometry method was established to quantify Nob, a hemolytic saponin, in
      rat blood and tissue homogenates. Standard curves were linear (r=0.9988-0.9995)
      over the range 50-5000ng/mL in blood and 100-10000ng/g in tissues. The lower
      limit of quantification (LLOQ) was 50ng/mL for Nob. The novel method was rapid,
      accurate, highly sensitive and highly selective. Using this method, the
      pharmacokinetics and biodistribution of Nob liposome and Nob solution in Sprague
      Dawley rats after a single intravenous dose of 1mg/kg were then investigated. Nob
      was cleared slowly from circulation. There was no significant difference of the
      pharmacokinetic parameters in blood between Nob solution and Nob liposome. The
      highest AUC of Nob was observed in liver for the two groups, followed by spleen,
      lungs, kidney and heart. Compared with Nob solution, Nob liposome showed much
      higher AUC in liver and spleen and much lower AUC in kidney, heart and lung,
      which might be one important reason for the decreased toxicity of Nob. 

PMID- 24911549
TI  - Determination of total iodine in serum and urine samples by ion chromatography
      with pulsed amperometric detection - studies on analyte loss, optimization of
      sample preparation procedures, and validation of analytical method.
AB  - A fast, accurate and precise ion chromatography method with pulsed amperometric
      detection was applied to evaluate a variety of parameters affecting the
      determination of total iodine in serum and urine of 81 subjects, including 56
      obese and 25 healthy Polish children. The sample pretreatment methods were
      carried out in a closed system and with the assistance of microwaves. Both
      alkaline and acidic digestion procedures were developed and optimized to find the
      simplest combination of reagents and the appropriate parameters for digestion
      that would allow for the fastest, least time consuming and most cost-effective
      way of analysis. A good correlation between the certified and the measured
      concentrations was achieved. The best recoveries (96.8% for urine and 98.8% for
      serum samples) were achieved using 1ml of 25% tetramethylammonium hydroxide
      solution within 6min for 0.1ml of serum/urine samples. Using 0.5ml of 65% nitric
      acid solution the best recovery (95.3%) was obtained when 7min of effective
      digestion time was used. Freeze-thaw stability and long-term stability were
      checked. After 24 weeks 14.7% loss of iodine in urine, and 10.9% in serum samples
      occurred. For urine samples, better correlation (R(2)=0.9891) of various sample
      preparation procedures (alkaline digestion and application of OnGuard RP
      cartidges) was obtained. Significantly lower iodide content was found in samples
      taken from obese children. Serum iodine content in obese children was markedly
      variable in comparison with the healthy group, whereas the difference was less
      evident when urine samples were analyzed. The mean content in serum was 59.12+/
      8.86MUg/L, and in urine 98.26+/-25.93 for obese children when samples were
      prepared by the use of optimized alkaline digestion reinforced by microwaves. In
      healthy children the mean content in serum was 82.58+/-6.01MUg/L, and in urine
      145.76+/-31.44MUg/L. 

PMID- 24911550
TI  - Massive pontine microbleeds in a patient with CADASIL.

PMID- 24911551
TI  - Test-retest reliability of concurrently recorded steady-state and somatosensory
      evoked potentials in somatosensory sustained spatial attention.
AB  - We investigated the test-retest reliability of sustained spatial attention
      modulation of steady-state somatosensory evoked potentials (SSSEPs) and the N140
      component of the somatosensory evoked potentials (SEPs). Participants attended to
      one or both hands to perform a target detection task while concurrent mechanical
      vibrations were presented for 4500ms to both hands in two recording sessions.
      Results revealed that the amplitude and the attentional modulation of SSSEPs had
      high test-retest reliability, while the test-retest reliability for the N140
      component was low. SSSEPs for stimuli with focused and divided attention had
      about the same amplitude. For the N140 component only the stimuli with focused
      attention were significantly enhanced. We found greater habituation effects for
      the N140 compared to SSSEP amplitudes but attentional modulation was unaffected
      in both signals. Given the great test-retest reliability of SSSEP amplitude
      modulation with attention, SSSEPs serve as an excellent tool for studying
      sustained spatial attention in somatosensation. 

PMID- 24911553
TI  - Unusual presentation of inflammatory linear verrucous epidermal naevus mimicking
      linear psoriasis successfully treated with oral retinoid.

PMID- 24911552
TI  - Age-related changes in feature-based object memory retrieval as measured by event
      related potentials.
AB  - To investigate neural mechanisms that support semantic functions in aging, we
      recorded scalp EEG during an object retrieval task in 22 younger and 22 older
      adults. The task required determining if a particular object could be retrieved
      when two visual words representing object features were presented. Both age
      groups had comparable accuracy although response times were longer in older
      adults. In both groups a left fronto-temporal negative potential occurred at
      around 750ms during object retrieval, consistent with previous findings (Brier,
      Maguire, Tillman, Hart, & Kraut, 2008). In only older adults, a later positive
      frontal potential was found peaking between 800 and 1000ms during no retrieval.
      These findings suggest younger and older adults employ comparable neural
      mechanisms when features clearly facilitate retrieval of an object memory, but
      when features yield no retrieval, older adults use additional neural resources to
      engage in a more effortful and exhaustive search prior to making a decision. 

PMID- 24911554
TI  - The changes of 8-OHdG, hOGG1, APE1 and Pol beta in lenses of patients with age
      related cataract.
AB  - PURPOSE: To evaluate the changes of oxidative DNA damage (in the form of 8-OHdG)
      and three key DNA base-excision repair (BER) proteins, human 8-oxoguanine DNA
      glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1) and DNA
      polymerase beta (Pol beta), in lens epithelium cells (LECs), cortex and nucleus
      of lenses with age-related cataract (ARC) and age-matched controls. METHODS: A
      total of 90 patients with ARC and 21 control subjects were enrolled. The samples
      included the anterior lens capsules (mainly composed of LECs) and various
      portions of lens. An ELISA assay was used to assess the 8-OHdG levels of genomic
      DNA extracted. Immunofluorescence and Western blot were used to analyze the
      localization and quantification of three BER proteins, respectively. RESULTS: The
      8-OHdG levels in lenses with ARC were higher than those of controls, and were not
      different among ARC subtypes. The 8-OHdG levels were the highest in the nucleus,
      followed by the LECs and cortex. The repair proteins were predominantly detected
      in the cellular nuclei of the LECs and superficial cortical cells. In the LECs,
      the protein levels of the three BER enzymes were higher in ARC than in controls.
      In the cortex, a downward trend of the levels of three BER enzymes was found with
      the increasing opaque degrees. In the nucleus, no enzymes were detected.
      CONCLUSIONS: Our findings indicate that the oxidative DNA damage increases in
      lenses with ARC, and the three BER enzymes compensatively increase in the LECs,
      while decreasing in the opaque cortex. The results suggest that the oxidative DNA
      damage may be related ARC and the alteration of DNA repair enzyme levels in ARC
      is associated with the location and opaque degrees of lens.

PMID- 24911555
TI  - Molecular mechanism regulating myosin and cardiac functions by ELC.
AB  - The essential myosin light chain (ELC) is involved in modulation of force
      generation of myosin motors and cardiac contraction, while its mechanism of
      action remains elusive. We hypothesized that ELC could modulate myosin stiffness
      which subsequently determines its force production and cardiac contraction.
      Therefore, we generated heterologous transgenic mouse (TgM) strains with
      cardiomyocyte-specific expression of ELC with human ventricular ELC (hVLC-1;
      TgM(hVLC-1)) or E56G-mutated hVLC-1 (hVLC-1(E56G); TgM(E56G)). hVLC-1 or hVLC
      1(E56G) expression in TgM was around 39% and 41%, respectively of total VLC-1.
      Laser trap and in vitro motility assays showed that stiffness and actin sliding
      velocity of myosin with hVLC-1 prepared from TgM(hVLC-1) (1.67 pN/nm and 2.3
      MUm/s, respectively) were significantly higher than myosin with hVLC-1(E56G)
      prepared from TgM(E56G) (1.25 pN/nm and 1.7 MUm/s, respectively) or myosin with
      mouse VLC-1 (mVLC-1) prepared from C57/BL6 (1.41 pN/nm and 1.5 MUm/s,
      respectively). Maximal left ventricular pressure development of isolated perfused
      hearts in vitro prepared from TgM(hVLC-1) (80.0 mmHg) were significantly higher
      than hearts from TgM(E56G) (66.2 mmHg) or C57/BL6 (59.3+/-3.9 mmHg). These
      findings show that ELCs decreased myosin stiffness, in vitro motility, and
      thereby cardiac functions in the order hVLC-1>hVLC-1(E56G)~mVLC-1. They also
      suggest a molecular pathomechanism of hypertrophic cardiomyopathy caused by hVLC
      1 mutations.

PMID- 24911556
TI  - Hormonogenic donor Tyr2522 of bovine thyroglobulin. Insight into preferential T3
      formation at thyroglobulin carboxyl terminus at low iodination level.
AB  - A tryptic fragment (b5TR,NR), encompassing residues 2515-2750, was isolated from
      a low-iodine (0.26% by mass) bovine thyroglobulin, by limited proteolysis with
      trypsin and preparative, continuous-elution SDS-PAGE. The fragment was digested
      with Asp-N endoproteinase and analyzed by reverse-phase HPLC electrospray
      ionization quadrupole time-of-flight mass spectrometry, revealing the formation
      of: 3-monoiodotyrosine and dehydroalanine from Tyr2522; 3-monoiodotyrosine from
      Tyr2555 and Tyr2569; 3-monoiodotyrosine and 3,5-diiodotyrosine from Tyr2748. The
      data presented document, by direct mass spectrometric identifications, efficient
      iodophenoxyl ring transfer from monoiodinated hormonogenic donor Tyr2522 and
      efficient mono- and diiodination of hormonogenic acceptor Tyr2748, under
      conditions which permitted only limited iodination of Tyr2555 and Tyr2569, in low
      iodine bovine thyroglobulin. The present study thereby provides: (1) a rationale
      for the preferential synthesis of T3 at the carboxy-terminal end of
      thyroglobulin, at low iodination level; (2) confirmation for the presence of an
      interspecifically conserved hormonogenic donor site in the carboxy-terminal
      domain of thyroglobulin; (3) solution for a previous uncertainty, concerning the
      precise location of such donor site in bovine thyroglobulin. 

PMID- 24911557
TI  - An update on the thrombotic microangiopathies hemolytic uremic syndrome (HUS) and
      thrombotic thrombocytopenic purpura (TTP).

PMID- 24911558
TI  - Spectrum of complement-mediated thrombotic microangiopathies: pathogenetic
      insights identifying novel treatment approaches.
AB  - Thrombotic microangiopathy (TMA) is a rare but severe disorder characterized by
      endothelial cell activation and thrombus formation. It manifests with the triad
      of hemolytic anemia, thrombocytopenia, and organ failure. Prompt diagnosis and
      treatment initiation are crucial for long-term outcome. TMA often manifests
      subsequent to infectious events, of which (enterohemorrhagic) Escherichia coli is
      the most frequently reported. TMA also occurs on the background of
      genetic/autoimmune defects in the complement system (atypical hemolytic uremic
      syndrome [aHUS]) and underlying conditions, such as pregnancy, transplantation,
      drugs, other glomerulopathies, vasculitides, or metabolic defects. Complement
      activation or defects in its regulation have now been described in an increasing
      number of acquired diseases with TMA. Coinciding with this expanding spectrum of
      complement-mediated diseases, the question arises which patients might benefit
      from a complement-targeted therapy. Success of therapy depends on the individual
      contribution of complement activation in disease pathogenesis. The advent of
      eculizumab, a monoclonal antibody that blocks terminal complement activation, has
      markedly improved outcome and quality of life in patients with aHUS. This review
      discusses the contribution of complement and highlights its complex interaction
      with inflammation, coagulation, and the endothelium. Treatment experiences
      focusing on eculizumab therapy are discussed in detail across the emerging
      spectrum of complement-mediated thrombotic microangiopathies. 

PMID- 24911560
TI  - A clinical analysis of uterine artery embolisation in the treatment of placenta
      praevia or placenta praevia state.
AB  - The aim of this study was to investigate the efficiency of uterine artery
      embolisation (UAE) for postpartum haemorrhage (PPH) related to placenta praevia.
      A total of 45 women with placenta praevia or placenta praevia state underwent UAE
      before inducing labour. The locations of uterine artery and placenta were
      determined through selective and super-selective catheterisation into the
      internal iliac artery and uterine artery digital subtraction angiography (DSA).
      The target arteries were then super-selectively catheterised and embolised using
      small pieces of gelatin sponge. The above processes were repeated until the
      darkly stained areas of placenta were no longer developing. The success rate of
      UAE was 100%. There was no longer haemorrhage after embolisation for all the
      cases of labour induction and the average volume of blood loss was 56 ml. UAE is
      an effective, reliable and minimally traumatic treatment method for preventing
      postpartum haemorrhage after induction of labour in patients with placenta
      praevia state.

PMID- 24911559
TI  - Structural and Functional Support in the Prediction of Smoking Cessation in
      Caregivers of Children with Asthma.
AB  - Caregivers of children with asthma smoke at rates similar to the general
      population. Research on the relative importance of structural or functional
      social support in smoking cessation has been mixed. Participants were smokers (N
      = 154) who were caregivers of children with asthma. Both functional
      (Interpersonal Support Evaluation List) and structural social support (living
      with another smoker, partner status, and the proportion of smoking friends) were
      measured at baseline. Participants received an asthma-education and smoking
      cessation intervention based on Motivational Interviewing. Biochemically-verified
      abstinence was assessed at six months post treatment. Results indicated that
      functional support predicted smoking abstinence even when controlling for
      relevant covariates and structural support (OR = .896, p = .025). Exploratory
      analyses revealed that this effect was driven primarily by the self-esteem ISEL
      subscale. Smoking cessation that focuses on building general functional support,
      particularly self-esteem support, may be beneficial for smoking cessation in
      caregivers of children with asthma. 

PMID- 24911561
TI  - Wastewater microalgal production, nutrient removal and physiological adaptation
      in response to changes in mixing frequency.
AB  - Laminar flows are a common problem in high rate algal ponds (HRAP) due to their
      long channels and gentle mixing by a single paddlewheel. Sustained laminar flows
      may modify the amount of light microalgal cells are exposed to, increase the
      boundary layer between the cell and the environment and increase settling out of
      cells onto the pond bottom. To date, there has been little focus on the effects
      of the time between mixing events (frequency of mixing) on the performance of
      microalgae in wastewater treatment HRAPs. This paper investigates the performance
      of three morphologically distinct microalgae in wastewater treatment high rate
      algal mesocosms operated at four different mixing frequencies (continuous, mixed
      every 45 min, mixed every 90 min and no mixing). Microalgal performance was
      measured in terms of biomass concentration, nutrient removal efficiency, light
      utilisation and photosynthetic performance. Microalgal biomass increased
      significantly with increasing mixing frequency for the two colonial species but
      did not differ for the single celled species. All three species were more
      efficient at NH4-N uptake as the frequency of mixing increased. Increased
      frequency of mixing supported larger colonies with improved harvest-ability by
      gravity but at the expense of efficient light absorption and maximum rate of
      photosynthesis. However, maximum quantum yield was highest in the continuously
      mixed cultures due to higher efficiency of photosynthesis under light limited
      conditions. Based on these results, higher microalgal productivity, improved
      wastewater treatment and better gravity based harvest-ability can be achieved
      with the inclusion of more mixing points and reduced laminar flows in full-scale
      HRAP.

PMID- 24911562
TI  - An improved titration model reducing over estimation of total volatile fatty
      acids in anaerobic digestion of energy crop, animal slurry and food waste.
AB  - Titration methodologies have been used for the many years for low cost routine
      monitoring of full scale anaerobic digestion plants. These methodologies have
      been correlated to indicate the carbonate alkalinity and the volatile fatty acids
      (VFA) content within digesters. Two commonly used two end-point titration methods
      were compared using a dataset of 154 samples from energy crop and animal slurry
      digestates and were shown to be inaccurate in the estimation of tVFA. Using this
      dataset correlated with HPLC VFA analysis, two empirical bivariate linear
      regression equations were derived, where the validation dataset showed an
      absolute tVFA mean error improvement from +/-3386 and +/-3324 mg kg(-1) tVFA to
      +/-410 and +/-286 mg kg(-1) tVFA, respectively. The same equation was then
      applied to a food waste dataset where an absolute tVFA mean error was improved
      from +/-3828 to +/-576 mg kg(-1) tVFA. The newly derived titration equations can
      provide greater confidence in digester performance monitoring and are tools that
      can improve digester management.

PMID- 24911563
TI  - Aluminum-humic colloid formation during pre-coagulation for membrane water
      treatment: mechanisms and impacts.
AB  - Precoagulation has been widely used by low pressure membrane filtration (LPMF)
      plants to reduce membrane fouling and increase natural organic matter (NOM)
      removal. Formation of aluminum and aluminum-NOM moieties plays a fundamental role
      in this important water treatment process. This study comprehensively
      investigated the mechanisms of aluminum-NOM species formation during
      precoagulation and their impacts on LPMF performance. The results show that, at
      low alum doses, e.g. 0.5 mg and 1.0 mg Al L(-1), humic substances (HS) and Al
      species (amorphous Al(OH)3, or Al(OH)3(am)) reacted to form small Al(OH)3(am)-HS
      colloids. Increases in alum dose resulted in sequential transitions of the Al-HS
      moieties to larger particles and, eventually, precipitates. Compared to waters
      containing only naturally occurring organic colloids (OC) or HS, the coexistence
      of OC and HS facilitated the formation of Al-HS precipitates, thereby increasing
      the removal of HS by 7-15%, but the removal of OC was decreased by 3-20%.
      Interestingly, these transitions in Al-HS moieties did not affect membrane
      fouling. Both short-term and long-term filtration results demonstrate that OC,
      rather than the Al(OH)3(am)-HS colloids, primarily caused membrane fouling. These
      findings highlight the dynamics of particulate Al-NOM formation during
      precoagulation and its relationship with membrane fouling, which can be utilized
      to optimize the operation of integrated precoagulation-LPMF systems on full-scale
      installations.

PMID- 24911564
TI  - Social goals, aggression, peer preference, and popularity: longitudinal links
      during middle school.
AB  - Social goals are associated with behaviors and adjustment among peers. However,
      it remains unclear whether goals predict adolescent social development. We
      examined prospective associations among goals, physical and relational
      aggression, social preference, and popularity during middle school (N = 384
      participants, ages 12-14 years). Agentic (status, power) goals predicted
      increased relational aggression and communal (closeness) goals predicted
      decreased physical aggression. Popularity predicted increases and preference
      predicted decreases in both forms of aggression. Goals moderated longitudinal
      links between aggression and popularity: Aggression predicted increases in
      popularity and vice versa for youth with higher agentic goals, and popularity
      predicted increases in physical aggression for youth with higher agentic and
      lower communal goals. Implications for research on social goals, aggression, and
      popularity are discussed.

PMID- 24911565
TI  - How do children share information in groups?
AB  - Group decision making should be particularly beneficial when group members share
      unique information, because then a group can make a better decision than each
      group member alone. This study examined how elementary-school children share
      unique information during group decision making. Seventy-nine groups of 3 same
      sex and same-age 7- and 9-year-old children (N = 237) had to decide which 1 of 2
      hypothetical candidates should play the lead role in a school musical. When
      information was unshared, group members had to exchange their uniquely held
      information to identify the best candidate. Only a minority of groups picked the
      best candidate when information was unshared. Yet, groups of 7-year-old children
      were better at identifying the best candidate and were less likely to focus on
      the discussion of shared information than groups of 9-year-olds. These findings
      are interpreted with reference to processes underlying information sharing in
      groups, namely collective information sampling, preference-consistent evaluation,
      and collaborative inhibition/intersubjectivity.

PMID- 24911566
TI  - Young children's understanding of denial.
AB  - Although a fair amount is known about young children's production of negation,
      little is known about their comprehension. Here, we focus on arguably the most
      complex basic form, denial, and how young children understand denial, when it is
      expressed in response to a question with gesture, single word, or sentence. One
      hundred twenty-six children in 3 age groups (Ms = 1 year 9 months, 2 years 0
      months, and 2 years 4 months) witnessed an adult look into 1 of 2 buckets and
      then, in response to a question about whether the toy was in there, communicate
      either something positive (positive head nod, "yes," "it is in this bucket") or
      negative (negative head shake, "No," "It's not in this bucket"). The youngest
      children did not search differently in response to any of the communicative cues
      (nor in response to an additional cue using both gesture and single word).
      Children at 2 years 0 months searched at above-chance levels only in response to
      the negative word and negative sentence. Children at 2 years 4 months were
      successful with all 3 types of cues in both positive and negative modalities,
      with the exception of the positive sentence. Young children thus seem to
      understand the denial of a statement before they understand its affirmation, and
      they understand linguistic means of expressing denial before they understand
      gestural means.

PMID- 24911567
TI  - Socio-emotional skills, behavior problems, and Spanish competence predict the
      acquisition of English among English language learners in poverty.
AB  - This article analyzes the role that individual differences in children's
      cognitive, Spanish competence, and socio-emotional and behavioral skills play in
      predicting the concurrent and longitudinal acquisition of English among a large
      sample of ethnically diverse, low-income, Hispanic preschool children.
      Participants assessed at age 4 for language, cognitive, socio-emotional, and
      behavioral skills were followed through kindergarten. Multivariate analyses
      demonstrated that Spanish-speaking preschoolers with greater initiative, self
      control, and attachment and fewer behavior problems at age 4 were more successful
      in obtaining English proficiency by the end of kindergarten compared to those
      initially weaker in these skills, even after controlling for cognitive/language
      skills and demographic variables. Also, greater facility in Spanish at age 4
      predicted the attainment of English proficiency. Social and behavioral skills and
      proficiency in Spanish are valuable resources for low-income English language
      learners during their transition to school.

PMID- 24911568
TI  - Parental bonds, attachment anxiety, media susceptibility, and body
      dissatisfaction: a mediation model.
AB  - The developmental trajectory of body image dissatisfaction is unclear.
      Researchers have investigated sociocultural and developmental risk factors;
      however, the literature needs an integrative etiological model. In 2009, Cheng
      and Mallinckrodt proposed a dual mediation model, positing that poor-quality
      parental bonds, via the mechanisms of heightening romantic attachment anxiety and
      thin-ideal media internalization, increases body dissatisfaction. We tested 2
      versions of this model, including an alternate model featuring attachment anxiety
      in close friendships. We recruited females ages 12-24, primarily from a mid-sized
      private religious university, to complete self-report measures. The participant
      sample was ethnically diverse, with approximately 40% endorsing minority status.
      Results showed that mother care and father care were negatively linked to
      friendship attachment anxiety and romantic attachment anxiety. Friendship and
      romantic attachment anxiety were positively linked to media susceptibility. Media
      susceptibility was positively linked to body image dissatisfaction. Mother care
      and father care were negatively, indirectly linked to body image dissatisfaction
      through the mediators of friendship attachment anxiety and media susceptibility.
      Mother care made a significant, albeit small, contribution to body image
      dissatisfaction after controlling for other variables. Overall, findings suggest
      that adverse parent-child relational factors may indirectly elevate body
      dissatisfaction, operating through attachment anxiety and susceptibility to
      sociocultural pressures.

PMID- 24911569
TI  - Friendship selection and influence in bullying and defending: effects of moral
      disengagement.
AB  - The current study examined the development of bullying and defending over a 1
      year period as related to friends' influence and individual and friends' moral
      disengagement (i.e., self-justification mechanisms that allow one to avoid moral
      self-censure of transgressive actions) in children and young adolescents. Via
      longitudinal social network analysis (RSiena), it was tested whether similarity
      between friends in bullying and defending developed over time due to friends'
      influence, while controlling for friendship selection processes, and whether
      there were differences in these processes between children (age 9-10 years; n =
      133; 42.9% girls) and young adolescents (age 11-14 years; n = 236; 40.6% girls).
      Results showed that individuals selected peers as friends who were similar in
      bullying and became more similar to friends in bullying over time, but only in
      early adolescence. Moreover, there was marginal support that friends' influence
      was stronger in young adolescents with higher moral disengagement. In early
      adolescence, bullying was also indirectly influenced through friends' moral
      disengagement, with different effects for boys and girls. With regard to
      defending, young adolescents maintained friendships with peers who were similar
      in defending, and became more similar to friends in terms of defending over time.
      These findings suggest important differences between late childhood and early
      adolescence in socialization processes and indicate that in early adolescence,
      friends' influence on the development of bullying is partially affected by moral
      disengagement.

PMID- 24911570
TI  - When do infants begin to follow a point?
AB  - Infants' understanding of a pointing gesture represents a major milestone in
      their communicative development. The current consensus is that infants are not
      capable of following a pointing gesture until 9-12 months of age. In this
      article, we present evidence from 4- and 6-month-old infants challenging this
      conclusion. Infants were tested with a spatial cueing paradigm in Experiment 1
      (500-ms stimulus-target onset asynchrony [SOA]) and Experiment 2 (100-ms SOA).
      The results revealed that the younger infants shifted their attention in the cued
      direction when presented with a pointing gesture and with a foil (i.e., same size
      and shape as pointing gesture) at both SOAs. Older infants shifted their
      attention only in response to the pointing gesture at 100-ms SOA. Experiment 3
      tested infants' preferences for the social stimulus (i.e., pointing gesture)
      relative to the foil and a non-social stimulus (i.e., an arrow). The results
      revealed that infants are biased to selectively attend to the pointing gesture.
      Taken together, these results suggest that 4- and 6-month-old infants are capable
      of preferentially selecting and following a pointing gesture. It is theorized
      that this early capacity assists infants in their developing understanding of
      triadic forms of communication.

PMID- 24911571
TI  - Early maternal employment and children's school readiness in contemporary
      families.
AB  - This study assessed whether previous findings linking early maternal employment
      to lower cognitive and behavioral skills among children generalized to modern
      families. Using a representative sample of children born in the United States in
      2001 (N = 10,100), ordinary least squares regression models weighted with
      propensity scores assessed links between maternal employment in the 2 years after
      childbearing and children's school readiness skills at kindergarten. There were
      neutral associations between maternal employment and children's school readiness,
      which were not differentiated by maternal time, stress, or wages. However, as
      nonmaternal household income decreased, maternal employment begun prior to 9
      months was linked with higher cognitive skills, while employment begun between 9
      and 24 months was linked with lower conduct problems.

PMID- 24911572
TI  - Ultrathin MnO(2) nanoflakes as efficient catalysts for oxygen reduction reaction.
AB  - Free-standing, ultrathin manganese dioxide nanoflakes were synthesized by
      cationic surfactant controlled reduction of KMnO4. MnO2 nanoflakes showed a much
      higher mass activity than other manganese based oxides as well as B and N doped
      nano carbons. The approach here demonstrates a facile chemical route towards
      efficient manganese dioxide catalysts. 

PMID- 24911573
TI  - Health literacy and the pharmacological treatment of anxiety disorders: a
      systematic review.
AB  - OBJECTIVE: Anxiety disorders are treatable conditions, but many affected
      individuals neither seek professional help nor adhere to recommended
      pharmacological treatments. Increasing the health literacy of people with (or at
      risk of) anxiety disorders may encourage treatment-seeking and adherence to
      recommended interventions. Aims of this study were to review the literature
      relating to health literacy in the treatment of anxiety disorders, focusing on
      results on public opinion on psychotropic medications and its effectiveness in
      improving access to psychiatric health care and the actual use of medications.
      METHODS: A computerized literature search of the published literature on mental
      health literacy was undertaken, focusing on the question of whether increased
      mental health literacy led to increased treatment-seeking and pharmacotherapy
      adherence in individuals with anxiety disorders. RESULTS: Twelve relevant
      articles were identified. All reported that improving mental health literacy
      leads to raised awareness, and in 10 out of 12 studies, increased help-seeking.
      However, there is currently no unequivocal evidence to show that increasing
      health literacy leads to increased use of medication in any psychiatric disorder,
      including anxiety disorders. Two studies show that knowledge of presumed
      biological mechanisms can predict use of psychotropic medication, including
      antidepressants, in psychiatric disorders, however, not specifically in anxiety
      disorders. CONCLUSION: There have been few investigations of health literacy
      focused on psychotropic medications. Given the prevalence, burden and sub-optimal
      recognition, and treatment of anxiety disorders, further work is needed to
      determine whether increased mental health literacy is associated with treatment
      seeking and medication adherence in patients with these disorders. Copyright (c)
      2014 John Wiley & Sons, Ltd.

PMID- 24911574
TI  - Celecoxib: a new augmentation strategy for depressive mood episodes. A systematic
      review and meta-analysis of randomized placebo-controlled trials.
AB  - OBJECTIVE: The aim of this research was to perform a systematic review to
      identify all randomized controlled trials (RCTs) evaluating the efficacy and
      safety of add-on celecoxib for treatment of depressive mood episodes. METHODS:
      Four electronic databases were systematically searched from their inception to 8
      August 2013: PubMed, Cochrane Library (Cochrane Central Register of Controlled
      Trials), Scopus, and PsychINFO. Pooled difference in means of Hamilton Depression
      Rating Scale score, pooled odds ratio (OR) of treatment response, and pooled OR
      of remission were calculated as the main effect size. A random-effects model was
      used to pool the data across studies. RESULTS: Five RCTs (four unipolar
      depression studies and one bipolar depression study) were included in the
      systematic review for qualitative data synthesis. Moreover, quantitative results
      of four RCTs (unipolar depression studies) were meta-analyzed. The add-on
      celecoxib group had a statistically significant decrease in means of the Hamilton
      Depression Rating Scale score at week 4 (pooled difference in means=3.3, 95%CI
      [1.2-5.3], p=0.002) and week 6 (pooled difference in means=3.43, 95%CI [1.9-4.9],
      p<0.0001). The add-on celecoxib group also showed higher response (pooled OR=6.6,
      95%CI [2.5-17], p<0.0001) and remission rates (pooled OR=6.6, 95%CI [2.7-15.9],
      p<0.0001) compared with the placebo group. CONCLUSIONS: Celecoxib can be
      considered as an effective add-on treatment for unipolar depressive patients.
      Making conclusion regarding the efficacy and safety for longer duration warrants
      further studies with a larger sample size and longer follow-up duration.

PMID- 24911575
TI  - Relationship between the plasma concentration of paliperidone and the clinical
      and drug-induced extrapyramidal symptoms in elderly patients with schizophrenia.
AB  - OBJECTIVE: We investigated the relationship between the plasma concentration of
      paliperidone (PAL) and clinical and drug-induced extrapyramidal symptoms (EPS) in
      elderly patients with schizophrenia. METHODS: In this study, 15 patients with
      schizophrenia receiving risperidone were switched to PAL and treated for 12
      weeks. Their clinical symptoms were assessed using the Positive and Negative
      Syndrome Scale and the Clinical Global Impression-Severity of Illness Scale.
      Their EPS were assessed using the Drug-induced EPS Scale, Abnormal Involuntary
      Movement Scale, and Barnes Akathisia Scale at baseline and 12 weeks. Plasma
      concentrations were measured by the liquid chromatography-mass spectrometry/mass
      spectrometry method. RESULTS: The results revealed that there were significant
      correlations between the plasma concentration of PAL and improved Positive and
      Negative Syndrome Scale total, negative, and general psychopathology scores
      (p<0.05). However, the efficacy did not improve linearly with plasma level. No
      significant correlations were found between the PAL plasma concentration and the
      mean change from baseline in the Drug-induced EPS Scale total score, Barnes
      Akathisia Scale, or Abnormal Involuntary Movement Scale. CONCLUSIONS: The results
      of this research suggested that, in elderly patients, although none of an
      increased plasma concentration of PAL, a worsening of EPS, or an increase in
      prolactin level occurs, linear clinical efficacy may not be obtained.

PMID- 24911576
TI  - Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following
      oral coadministration of immediate-release morphine with ethanol in healthy male
      participants.
AB  - OBJECTIVE: This paper aimed to evaluate the effects of coadministered immediate
      release morphine and ethanol on safety, pharmacokinetic, and pharmacodynamic
      measures. METHODS: In the first stage of a randomized, double-blind, placebo
      controlled, crossover study, 16 healthy men with a history of moderate drinking
      received morphine 50 mg+ethanol 0.7 g/kg, morphine 50 mg+ethanol placebo, and
      morphine placebo+ethanol 0.7 g/kg. In the second stage, participants received
      either a lower (30 mg) or higher (80 mg) morphine dose (alone and in combination
      with ethanol) depending on their tolerability to treatments in stage 1. Safety,
      pharmacodynamic (including visual analog scales, pupillometry, capnography, and
      psychomotor and cognitive measures), and pharmacokinetic assessments were
      conducted. RESULTS: With the exception of one severe adverse event (AE), all
      others were mild or moderate in intensity. Morphine resulted in dose-related
      increases in AEs. When morphine was administered with ethanol, similar AEs were
      observed (dizziness, headache, somnolence, nausea, and vomiting), but these were
      sometimes more frequent compared with those observed with either drug alone. No
      consistent additive or interaction effects were observed on pharmacodynamic
      measures. Ethanol had no apparent effects on the pharmacokinetics of morphine or
      its metabolites. CONCLUSIONS: Coadministration of single doses of morphine and
      ethanol tested in this study did not affect the safety, pharmacodynamics, or
      pharmacokinetics of morphine or ethanol administered alone. Copyright (c) 2014
      John Wiley & Sons, Ltd.

PMID- 24911577
TI  - A single-dose, randomized, double-blind, double dummy, placebo and positive
      controlled, five-way cross-over study to assess the pharmacodynamic effects of
      lorediplon in a phase advance model of insomnia in healthy Caucasian adult male
      subjects.
AB  - OBJECTIVE: A 5-h phase advance model of insomnia was used to evaluate the
      efficacy of lorediplon, a new non-benzodiazepine hypnotic. METHODS: Thirty-five
      male, healthy subjects were included in a five-way randomized cross-over study.
      During each of the periods, sleep was recorded, and residual effects were
      measured. All subjects received lorediplon 1, 5, and 10 mg, placebo, and zolpidem
      10 mg (i.e., active control). RESULTS: Polysomnographic evaluation revealed that
      lorediplon (5 and 10 mg) significantly decreased wake after sleep onset (WASO)
      and increased total sleep time. Analysis by quarters of the night showed a
      progressive increasing effectiveness of lorediplon 10 mg across the first three
      quarters. Lorediplon increased non-rapid eye movement slow wave sleep and stage
      N2 sleep in the second and third quarters. The magnitude of these effects was
      dose related, with minimal effects seen with 1 mg. No residual effects were
      observed 13 h post dose. CONCLUSIONS: Lorediplon demonstrated a dose-dependent
      improvement in sleep, whereas zolpidem showed a more sustained WASO effect. No
      next-day hangover effects were observed. These sleep effects are also consistent
      with the pharmacokinetic profile of lorediplon. These results warrant clinical
      trials in patients with insomnia.

PMID- 24911578
TI  - Plasma dehydroepiandrosterone sulfate levels in patients with major depressive
      disorder correlate with remission during treatment with antidepressants.
AB  - OBJECTIVE: We attempted to investigate whether dehydroepiandrosterone sulfate
      (DHEA-S) levels are associated with remission of major depressive disorder by
      assessing scores on the 17-Item Structured Interview Guide for the Hamilton
      Depression before and after antidepressant treatment. METHODS: Plasma DHEA-S
      levels in 24 patients diagnosed with major depressive disorder on the basis of
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text
      revision) before and after antidepressant treatment, and 24 healthy, gender
      matched, and age-matched controls were measured using a radioimmunoassay kit.
      RESULTS: Plasma DHEA-S levels in patients were significantly higher than those in
      healthy controls. In patients who achieved remission after antidepressant
      treatment, plasma DHEA-S levels significantly declined compared with the levels
      before treatment. A significant correlation was observed between changes in DHEA
      S levels and Absence of Depressive and Anxious Mood scores, which are calculated
      from the 2-Item Structured Interview Guide for the Hamilton Depression rating as
      follows: severity of depressive mood and anxiety in patients before and after
      antidepressant treatment. CONCLUSIONS: These findings suggest that plasma DHEA-S
      levels can be used as a putative indicator of the state of remission in patients
      with major depressive disorder. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24911579
TI  - Cortisol awakening response and spatial working memory in man: a U-shaped
      relationship.
AB  - OBJECTIVE: The association between hypothalamic-pituitary-adrenal (HPA)-axis
      function and cognition has long been investigated. An inverted U-shaped
      relationship has been described between various measures of HPA-axis function and
      neuropsychological performance in animals and man. Work with glucocorticoid
      receptor manipulation has corroborated these findings, with particular effects
      observed in relation to spatial working memory (SWM). As HPA-axis dysfunction is
      frequently found in patients with psychiatric illness, research in this area has
      potential implications for the treatment of the commonly observed cognitive
      impairment in such disorders. Here, we present the results of a pilot study
      examining the relationship between cortisol awakening response (CAR) and
      cognitive functions known to be susceptible to HPA-axis manipulation. METHODS:
      Nineteen healthy male volunteers were recruited, and their CAR and performance in
      a task of SWM were assessed. RESULTS: A highly significant quadratic relationship
      was observed between the CAR and SWM error rate (R(2)=0.63, p=0.001). CONCLUSION:
      We provide novel evidence supporting the existence of an inverted U-shaped
      relationship between corticosteroid levels and cognitive function in humans.

PMID- 24911580
TI  - Gender moderates the effect of oxytocin on social judgments.
AB  - OBJECTIVE: The neuropeptide oxytocin is implicated in social processing, and
      recent research has begun to explore how gender relates to the reported effects.
      This study examined the effects of oxytocin on social affective perception and
      learning. METHODS: Forty-seven male and female participants made judgments of
      faces during two different tasks, after being randomized to either double-blinded
      intranasal oxytocin or placebo. In the first task, "unseen" affective stimuli
      were presented in a continuous flash suppression paradigm, and participants
      evaluated faces paired with these stimuli on dimensions of competence,
      trustworthiness, and warmth. In the second task, participants learned affective
      associations between neutral faces and affective acts through a gossip learning
      procedure and later made affective ratings of the faces. RESULTS: In both tasks,
      we found that gender moderated the effect of oxytocin, such that male
      participants in the oxytocin condition rated faces more negatively, compared with
      placebo. The opposite pattern of findings emerged for female participants: they
      rated faces more positively in the oxytocin condition, compared with placebo.
      CONCLUSIONS: These findings contribute to a small but growing body of research
      demonstrating differential effects of oxytocin in men and women.

PMID- 24911582
TI  - Sus1p facilitates pre-initiation complex formation at the SAGA-regulated genes
      independently of histone H2B de-ubiquitylation.
AB  - Sus1p is a common component of transcriptional co-activator, SAGA (Spt-Ada-Gcn5
      Acetyltransferase), and mRNA export complex, TREX-2 (Transcription-export 2), and
      is involved in promoting transcription and mRNA export. However, it is not
      clearly understood how Sus1p promotes transcription. Here, we show that Sus1p is
      predominantly recruited to the upstream activating sequence of a SAGA-dependent
      gene, GAL1, under transcriptionally active conditions as a component of SAGA to
      promote the formation of pre-initiation complex (PIC) at the core promoter and,
      consequently, transcriptional initiation. Likewise, Sus1p promotes the PIC
      formation at other SAGA-dependent genes and hence transcriptional initiation.
      Such function of Sus1p in promoting PIC formation and transcriptional initiation
      is not mediated via its role in regulation of SAGA's histone H2B de
      ubiquitylation activity. However, Sus1p's function in regulation of histone H2B
      ubiquitylation is associated with transcriptional elongation, DNA repair and
      replication. Collectively, our results support that Sus1p promotes PIC formation
      (and hence transcriptional initiation) at the SAGA-regulated genes independently
      of histone H2B de-ubiquitylation and further controls transcriptional elongation,
      DNA repair and replication via orchestration of histone H2B ubiquitylation, thus
      providing distinct functional insights of Sus1p in regulation of DNA transacting
      processes. 

PMID- 24911584
TI  - Producing recombinant therapeutic glycoproteins with enhanced sialylation using
      CHO-gmt4 glycosylation mutant cells.
AB  - Recombinant glycoprotein drugs require proper glycosylation for optimal
      therapeutic efficacy. Glycoprotein therapeutics are rapidly removed from
      circulation and have reduced efficacy if they are poorly sialylated. Ricinus
      communis agglutinin-I (RCA-I) was found highly toxic to wild-type CHO-K1 cells
      and all the mutants that survived RCA-I treatment contained a dysfunctional N
      acetylglucosaminyltransferase I (GnT I) gene. These mutants are named CHO-gmt4
      cells. Interestingly, upon restoration of GnT I, the sialylation of a model
      glycoprotein, erythropoietin, produced in CHO-gmt4 cells was shown to be superior
      to that produced in wild-type CHO-K1 cells. This addendum summarizes the
      applicability of this cell line, from transient to stable expression of the
      recombinant protein, and from a lab scale to an industrial scale perfusion
      bioreactor. In addition, CHO-gmt4 cells can be used to produce glycoproteins with
      mannose-terminated N-glycans. Recombinant glucocerebrosidase produced by CHO-gmt4
      cells will not require glycan remodeling and may be directly used to treat
      patients with Gaucher disease. CHO-gmt4 cells can also be used to produce other
      glycoprotein therapeutics which target cells expressing mannose receptors. 

PMID- 24911583
TI  - The yin and yang of bacterial resilience in the human gut microbiota.
AB  - The human gut is home to trillions of microbes that form a symbiotic relationship
      with the human host. During health, the intestinal microbiota provides many
      benefits to the host and is generally resistant to colonization by new species;
      however, disruption of this complex community can lead to pathogen invasion,
      inflammation, and disease. Restoration and maintenance of a healthy gut
      microbiota composition requires effective therapies to reduce and prevent
      colonization of harmful bacteria (pathogens) while simultaneously promoting
      growth of beneficial bacteria (probiotics). Here we review the mechanisms by
      which the host modulates the gut community composition during health and disease,
      and we discuss prospects for antibiotic and probiotic therapy for restoration of
      a healthy intestinal community following disruption. 

PMID- 24911585
TI  - Thermodynamics of the DNA damage repair steps of human 8-oxoguanine DNA
      glycosylase.
AB  - Human 8-oxoguanine DNA glycosylase (hOGG1) is a key enzyme responsible for
      initiating the base excision repair of 7,8-dihydro-8-oxoguanosine (oxoG). In this
      study a thermodynamic analysis of the interaction of hOGG1 with specific and non
      specific DNA-substrates is performed based on stopped-flow kinetic data. The
      standard Gibbs energies, enthalpies and entropies of specific stages of the
      repair process were determined via kinetic measurements over a temperature range
      using the van't Hoff approach. The three steps which are accompanied with changes
      in the DNA conformations were detected via 2-aminopurine fluorescence in the
      process of binding and recognition of damaged oxoG base by hOGG1. The
      thermodynamic analysis has demonstrated that the initial step of the DNA
      substrates binding is mainly governed by energy due to favorable interactions in
      the process of formation of the recognition contacts, which results in negative
      enthalpy change, as well as due to partial desolvation of the surface between the
      DNA and enzyme, which results in positive entropy change. Discrimination of non
      specific G base versus specific oxoG base is occurring in the second step of the
      oxoG-substrate binding. This step requires energy consumption which is
      compensated by the positive entropy contribution. The third binding step is the
      final adjustment of the enzyme/substrate complex to achieve the catalytically
      competent state which is characterized by large endothermicity compensated by a
      significant increase of entropy originated from the dehydration of the DNA
      grooves. 

PMID- 24911586
TI  - Dysregulated microRNA clusters in response to retinoic acid and CYP26B1 inhibitor
      induced testicular function in dogs.
AB  - Spermatogenesis is a multistep synchronized process. Diploid spermatogonia
      differentiate into haploid spermatozoa following mitosis, meiosis and
      spermiogenesis. Division and differentiation of male germ cells is achieved
      through the sequential expression of several genes. Numerous mRNAs in the
      differentiating germ cells undergo post-transcriptional and translational
      regulation. MiRNAs are powerful negative regulators of mRNA transcription,
      stability, and translation and recognize their mRNA targets through base-pairing.
      Retinoic acid (RA) signaling is essential for spermatogenesis and testicular
      function. Testicular RA level is critical for RA signal transduction. This study
      investigated the miRNAs modulation in an RA- induced testicular environment
      following the administration of all-trans RA (2 uM) and CYP26B1- inhibitor (1 uM)
      compared to control. Eighty four canine mature miRNAs were analyzed and their
      expression signatures were distinguished using real-time PCR based array
      technology. Of the miRNAs analyzed, miRNA families such as miR-200 (cfa-miR-200a,
      cfa-miR-200b and cfa-miR-200c), Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa
      let-7g and cfa-let-7f), miR-125 (cfa-miR-125a and cfa-miR-125b), miR-146 (cfa-miR
      146a and cfa-miR-146b), miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c), miR-23
      (cfa-miR-23a and cfa-miR-23b), cfa-miR-184, cfa-miR-214 and cfa-miR-141 were
      significantly up-regulated with testicular RA intervention via administration of
      CYP26B1 inhibitor and all-trans-RA and species of miRNA such as cfa-miR-19a, cfa
      miR-29b, cfa-miR-29c, cfa-miR-101 and cfa-miR-137 were significantly down
      regulated. This study explored information regarding chromosome distribution,
      human orthologous sequences and the interaction of target genes of miRNA families
      significantly distinguished in this study using prediction algorithms. This study
      importantly identified dysregulated miRNA species resulting from RA-induced
      spermatogenesis. The present contribution serves as a useful resource for further
      elucidation of the regulatory role of individual miRNA in RA synchronized canine
      spermatogenesis. 

PMID- 24911587
TI  - Necdin promotes ubiquitin-dependent degradation of PIAS1 SUMO E3 ligase.
AB  - Necdin, a pleiotropic protein that promotes differentiation and survival of
      mammalian neurons, is a member of MAGE (melanoma antigen) family proteins that
      share a highly conserved MAGE homology domain. Several MAGE proteins interact
      with ubiquitin E3 ligases and modulate their activities. However, it remains
      unknown whether MAGE family proteins interact with SUMO (small ubiquitin-like
      modifier) E3 ligases such as PIAS (protein inhibitor of activated STAT) family,
      Nsmce2/Mms21 and Cbx4/Pc2. In the present study, we examined whether necdin
      interacts with these SUMO E3 ligases. Co-immunoprecipitation analysis revealed
      that necdin, MAGED1, MAGEF1 and MAGEL2 bound to PIAS1 but not to Nsmce2 or Cbx4.
      These SUMO E3 ligases bound to MAGEA1 but failed to interact with necdin-like
      2/MAGEG1. Necdin bound to PIAS1 central domains that are highly conserved among
      PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates
      STAT1 and PML (promyelocytic leukemia protein). Remarkably, necdin promoted
      degradation of PIAS1 via the ubiquitin-proteasome pathway. In transfected HEK293A
      cells, amino- and carboxyl-terminally truncated mutants of PIAS1 bound to necdin
      but failed to undergo necdin-dependent ubiquitination. Both PIAS1 and necdin were
      associated with the nuclear matrix, where the PIAS1 terminal deletion mutants
      failed to localize, implying that the nuclear matrix is indispensable for necdin
      dependent ubiquitination of PIAS1. Our data suggest that necdin suppresses PIAS1
      both by inhibiting SUMO E3 ligase activity and by promoting ubiquitin-dependent
      degradation. 

PMID- 24911588
TI  - First insight into the genotypic diversity of clinical Mycobacterium tuberculosis
      isolates from Gansu Province, China.
AB  - BACKGROUND: Investigations of Mycobacterium tuberculosis genetic diversity in
      China have indicated a significant regional distribution. The aim of this study
      was to characterize the genotypes of clinical M. tuberculosis isolates obtained
      from Gansu, which has a special geographic location in China.
      METHODOLOGY/PRINCIPAL FINDINGS: A total of 467 clinical M. tuberculosis strains
      isolated in Gansu Province were genotyped by 15-locus mycobacterial interspersed
      repetitive units-variable number tandem repeats (MIRU-VNTR) and spoligotyping.
      The results showed that 445 isolates belonged to six known spoligotype lineages,
      whereas 22 isolates were unknown. The Beijing genotype was the most prevalent
      (87.58%, n = 409), while the shared type 1 was the dominant genotype (80.94%, n =
      378). The second most common lineage was the T lineage, with 25 isolates (5.35%),
      followed by the H lineage with 5 isolates (1.07%), the MANU family (0.64%, 3
      isolates), the U family (0.43%, 2 isolates) and the CAS lineage with 1 isolate
      (0.21%). By using the VNTR15China method, we observed 15 groups and 228 genotypes
      among the 467 isolates. We found no association between the five larger groups
      (including the Beijing genotype) and sex, age, or treatment status, and there was
      no noticeable difference in the group analysis in different areas. In the present
      study, seven of the 15 MIRU-VNTR loci were highly or moderately discriminative
      according to their Hunter-Gaston discriminatory index. CONCLUSIONS/SIGNIFICANCE:
      The Beijing genotype is the predominant genotype in Gansu province. We confirm
      that VNTR15China is suitable for typing Beijing strains in China and that it has
      a better discriminatory power than spoligotyping. Therefore, the use of both
      methods is the most suitable for genotyping analysis of M. tuberculosis.

PMID- 24911589
TI  - Altered substrate specificity of the Pterygoplichthys sp. (Loricariidae) CYP1A
      enzyme.
AB  - Ethoxyresorufin is a classical substrate for vertebrate CYP1A enzymes. In
      Pterygoplichthys sp. (Loricariidae) this enzyme possesses 48 amino acids
      substitutions compared to CYP1A sequences from other vertebrate species. These
      substitutions or a certain subset substitution are responsible for the non
      detection of the EROD reaction in this species liver microsomes. In the present
      study, we investigated the catalytic activity of Pterygoplichthys sp. CYP1A
      toward 15 potential substrates in order to understand the substrate preferences
      of this modified CYP1A. The fish gene was expressed in yeast and the accumulation
      of the protein was confirmed by both the characteristic P450-CO absorbance
      spectra and by detection with monoclonal antibodies. Catalytic activities were
      assayed with yeast microsomes and four resorufin ethers, six coumarin derivates,
      three flavones, resveratrol and ethoxyfluoresceinethylester. Results demonstrated
      that the initial velocity pattern of this enzyme for the resorufin derivatives is
      different from the one described for most vertebrate CYP1As. The initial velocity
      for the activity with the coumarin derivatives is several orders of magnitude
      higher than with the resorufins, i.e. the turnover number (kcat) for ECOD is 400*
      higher than for EROD. Nonetheless, the specificity constant (kcat/km) for EROD is
      only slightly higher than for ECOD. EFEE is degraded at a rate comparable to the
      resorufins. Pterygoplichthys sp. CYP1A also degrades 7-methoxyflavone and beta
      naphthoflavone but not resveratrol and chrysin. These results indicate a
      divergent substrate preference for Pterygoplichthys sp. CYP1A, which may be
      involved in the adaptation of Loricariidae fish to their particular environment
      and feeding habits. 

PMID- 24911590
TI  - The joint effects on Photobacterium phosphoreum of metal oxide nanoparticles and
      their most likely coexisting chemicals in the environment.
AB  - Metal oxide nanoparticles (NPs) have been used increasingly and are likely to
      accumulate in natural water bodies, where they encounter and interact with other
      environmental chemicals. These interactions result in joint effects on biological
      systems and the environment. However, compared with the intensive research
      examining the toxicities of individual NPs, the toxicities of NP mixtures remain
      relatively unexplored. In this work, we studied the joint effects of NPs and
      their most likely coexisting chemicals in the environment, including NPs with
      different compositions, humic substances, and surfactants. Our results indicate
      that the joint effects of NP mixtures were usually simple addition, which is
      commonly adopted in real risk assessment. However, the joint effects obtained for
      mixtures that contained ZnO were exclusively associated with antagonism. In
      addition, the mixtures of NPs and surfactants resulted in complex joint effects,
      i.e., antagonistic, additive, and synergistic effects were found for the mixtures
      with ZnO, NiO, and Fe-oxide, respectively. Our study suggests that the
      assessments of the ecological risk of NPs, particularly ZnO NPs, should consider
      the impact of their coexisting chemicals in the environment. 

PMID- 24911591
TI  - Re: Al-Baghdadi O, Samarasinghe A, Wissa I. 2014. Cervical schistosomiasis.
      Journal of Obstetrics and Gynaecology 34:206.

PMID- 24911592
TI  - Anaerobic work calculated in cycling time trials of different length.
AB  - Previous research showed that gross efficiency (GE) declines during exercise and
      therefore influences the expenditure of anaerobic and aerobic resources. PURPOSE:
      To calculate the anaerobic work produced during cycling time trials of different
      length, with and without a GE correction. METHODS: Anaerobic work was calculated
      in 18 trained competitive cyclists during 4 time trials (500, 1000, 2000, and
      4000-m). Two additional time trials (1000 and 4000 m) that were stopped at 50% of
      the corresponding "full" time trial were performed to study the rate of the
      decline in GE. RESULTS: Correcting for a declining GE during time-trial exercise
      resulted in a significant (P<.001) increase in anaerobically attributable work of
      30%, with a 95% confidence interval of [25%, 36%]. A significant interaction
      effect between calculation method (constant GE, declining GE) and distance (500,
      1000, 2000, 4000 m) was found (P<.001). Further analysis revealed that the
      constant-GE calculation method was different from the declining method for all
      distances and that anaerobic work calculated assuming a constant GE did not
      result in equal values for anaerobic work calculated over different time-trial
      distances (P<.001). However, correcting for a declining GE resulted in a constant
      value for anaerobically attributable work (P=.18). CONCLUSIONS: Anaerobic work
      calculated during short time trials (<4000 m) with a correction for a declining
      GE is increased by 30% [25%, 36%] and may represent anaerobic energy
      contributions during high-intensity exercise better than calculating anaerobic
      work assuming a constant GE.

PMID- 24911593
TI  - Physician-perceived contradictions in end-of-life communication: toward a self
      report measurement scale.
AB  - Communication is undoubtedly a critical element of competent end-of-life care.
      However, physicians commonly lack communication skills in this particular care
      context. Theoretically grounded, evidence-based guidelines are needed to enhance
      physicians' communication with patients and their families in this important time
      of their lives. To address this need, this study tests and validates a
      Contradictions in End-of-Life Communication (CEOLC) scale, which disentangles the
      relational contradictions physicians commonly experience when communicating with
      end-of-life patients. Exploratory factors analysis confirmed the presence of
      eight physician-perceived dialectical tensions, reflecting three latent factors
      of (1) integration, (2) expression, and (3) dominance. Furthermore, a number of
      significant intercultural differences were found in cross-cultural comparisons of
      the scale in U.S., Swiss, and Italian physician samples. Thus, this investigation
      introduces a heuristic assessment tool that aids a better understanding of the
      dialectical contradictions physicians experience in their interactions with end
      of-life patients. The CEOLC scale can be used to gather empirical evidence that
      may eventually support the development of evidence-based guidelines and skills
      training toward improved end-of-life care. 

PMID- 24911594
TI  - Personal growth, grandmother engagement and satisfaction among non-custodial
      grandmothers.
AB  - OBJECTIVES: We investigated grandmothers' personal growth, their engagement with
      grandchildren, their satisfaction with this role and how personal growth was
      related to engagement and satisfaction. METHOD: One thousand two hundred and five
      grandmothers completed a survey containing questions about: personal resources
      (age, education, whether partnered or not, health); engagement with grandchildren
      (number of grandchildren, hours spent per week, frequency of activities,
      satisfaction with being a grandmother); and personal growth (life satisfaction,
      generativity). RESULTS: Participants had a positive sense of living productive
      and worthwhile lives with most reporting high scores on life satisfaction and
      generativity. Most were actively engaged with their grandchildren, participating
      in a wide range of activities. Active engagement was positively related to
      grandmother satisfaction. Hierarchical regressions showed that both life
      satisfaction and generativity were significantly predicted by grandmother
      resources and grandmother engagement. CONCLUSION: This group of grandmothers did
      not fit ageist stereotypes of disengagement and loss of function. Our study shows
      that grandmothering is a rewarding role, and women who engage with it have a
      positive sense of personal growth.

PMID- 24911595
TI  - Secretion and filamentation are mediated by the Candida albicans t-SNAREs Sso2p
      and Sec9p.
AB  - To study the role of late secretion in Candida albicans pathogenesis, we created
      conditional mutant C. albicans strains in which the t-SNARE-encoding genes SSO2
      or SEC9 were placed under the control of a tetracycline-regulated promoter. In
      repressing conditions, C. albicans tetR-SSO2 and tetR-SEC9 mutant strains were
      defective in cytokinesis and secretion of aspartyl proteases and lipases. The
      mutant strains also exhibited a defect in filamentation compared with controls,
      and thus, we followed the fate of the C. albicans Spitzenkorper, an assembly of
      secretory vesicles thought to act as a vesicle supply center for the growing
      hyphae. In the absence of Ca Sso2p, the Spitzenkorper dissipated within 5 h and
      thin-section electron microscopy revealed an accumulation of secretory vesicles.
      Moreover, the hyphal tip developed into a globular yeast-like structure rather
      than maintaining a typical narrow hyphae. These studies indicate that late
      secretory t-SNARE proteins in C. albicans are required for fundamental cellular
      processes and contribute to virulence-related attributes of C. albicans
      pathogenesis. Moreover, these results provide direct evidence for a key role of
      SNARE proteins in vesicle-mediated polarized hyphal growth of C. albicans. 

PMID- 24911597
TI  - Ovarian cancer biology and immunotherapy.
AB  - Ovarian cancer is the most lethal malignancy of the female reproductive system
      and the fifth leading cause of cancer death in women. In the year 2012 alone,
      United States had 22,280 new ovarian cancer cases and 15,500 deaths were
      reported. About 7%-10% of ovarian cancers result from an inherited tendency to
      develop the disease. Ovarian cancer has the ability to escape the immune system
      because of its pathological interactions between cancer cells and host immune
      cells in the tumor microenvironment create an immunosuppressive network that
      promotes tumor growth, protects the tumor from immune system. The levels of
      immune suppressive elements like regulatory T cells, plasmacytoid dendritic cells
      and cytokines such as IL-10, IL-6, TNF-alpha, and TGF-beta are elevated in the
      tumor microenvironment. Vascular endothelial growth factor is known to have an
      immune suppressing role besides its angiogenic role in the tumor
      microenvironment. Ovarian cancer is associated with high mortality partly due to
      difficulties in early diagnosis and development of metastases. These problems may
      overcome by developing accurate mouse models that should mimic the complexity of
      human ovarian cancer. Such animal models are better suited to understand
      pathophysiology, metastases, and also for preclinical testing of targeted
      molecular therapeutics. Immunotherapy is an area of active investigation and off
      late many clinical trials is ongoing to prevent disease progression. The main aim
      of dendritic cells vaccination is to stimulate tumor specific effector T cells
      that can reduce tumor size and induce immunological memory to prevent tumor
      relapse. 

PMID- 24911596
TI  - SOD1(G93A) transgenic mouse CD4(+) T cells mediate neuroprotection after facial
      nerve axotomy when removed from a suppressive peripheral microenvironment.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      involving motoneuron (MN) axonal withdrawal and cell death. Previously, we
      established that facial MN (FMN) survival levels in the SOD1(G93A) transgenic
      mouse model of ALS are reduced and nerve regeneration is delayed, similar to
      immunodeficient RAG2(-/-) mice, after facial nerve axotomy. The objective of this
      study was to examine the functionality of SOD1(G93A) splenic microenvironment,
      focusing on CD4(+) T cells, with regard to defects in immune-mediated
      neuroprotection of injured MN. We utilized the RAG2(-/-) and SOD1(G93A) mouse
      models, along with the facial nerve axotomy paradigm and a variety of cellular
      adoptive transfers, to assess immune-mediated neuroprotection of FMN survival
      levels. We determined that adoptively transferred SOD1(G93A) unfractionated
      splenocytes into RAG2(-/-) mice were unable to support FMN survival after
      axotomy, but that adoptive transfer of isolated SOD1(G93A) CD4(+) T cells could.
      Although WT unfractionated splenocytes adoptively transferred into SOD1(G93A)
      mice were able to maintain FMN survival levels, WT CD4(+) T cells alone could
      not. Importantly, these results suggest that SOD1(G93A) CD4(+) T cells retain
      neuroprotective functionality when removed from a dysfunctional SOD1(G93A)
      peripheral splenic microenvironment. These results also indicate that the
      SOD1(G93A) central nervous system microenvironment is able to re-activate CD4(+)
      T cells for immune-mediated neuroprotection when a permissive peripheral
      microenvironment exists. We hypothesize that a suppressive SOD1(G93A) peripheral
      splenic microenvironment may compromise neuroprotective CD4(+) T cell activation
      and/or differentiation, which, in turn, results in impaired immune-mediated
      neuroprotection for MN survival after peripheral axotomy in SOD1(G93A) mice. 

PMID- 24911599
TI  - Electron scattering from pyridine.
AB  - We have calculated cross sections for elastic and inelastic electron scattering
      from pyridine in the energy range 1 eV to 1 keV. The R-matrix and IAM-SCAR
      methods have been used for low and higher collision energies, respectively.
      Agreement with available theoretical data is good. We have also examined the
      formation of shape resonances and compared our results with existing experimental
      data. We compare the results with data for electron scattering from pyrimidine. 

PMID- 24911598
TI  - HBIG Remains Significant in the Era of New Potent Nucleoside Analogues for
      Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.
AB  - Advent of hepatitis B immunoglobulin (HBIG) as the mainstay of prophylaxis
      against hepatitis B recurrence after liver transplantation with antiviral drugs
      has resulted in excellent outcomes for liver transplantation in hepatitis B virus
      (HBV)-related cirrhosis in the last two decades. However, there is no consensus
      on a gold standard prophylaxis protocol and several controversies over the
      duration, dose, and route of administration of HBIG with or without different
      antivirals exist among liver transplantation centers. We present this review of
      different prophylaxis regimens including HBIG and antiviral monotherapy,
      combination of HBIG with antivirals, and withdrawal of HBIG and whole
      prophylaxis. HBIG monotherapy in either the intramuscular or the subcutaneous
      form is an accepted choice for prevention of HBV re-infection after liver
      transplantation in low risk patients. Withdrawal of HBIG monotherapy may be
      considered but should only occur after transitioning to an oral antiviral therapy
      such as adefovir, tenofovir, or entecavir. Lamivudine monotherapy may be
      associated with a higher recurrence rate compared to more potent antivirals. In
      high risk patients, intramuscular or subcutaneous HBIG in combination with an
      antiviral, most commonly lamivudine, is currently considered the standard of
      care. Complete discontinuation of all preventative therapy cannot be recommended
      at this time and should only be performed in the setting of a clinical trial.

PMID- 24911600
TI  - Comparison of surgical outcomes and patient satisfaction after 2 different
      rhinoplasty techniques.
AB  - Various methods of surgical treatment are defined in nasal deformities that cause
      nasal obstruction. Open technique septorhinoplasty is a method that is frequently
      used for this purpose. This study aims to compare surgical results of open
      technique septorhinoplasty operations with and without osteotomies. In addition,
      changes in the quality of life of patients before and after treatment were
      investigated, and the effects of the 2 methods on patients' quality of life were
      compared. METHODS: Patients with nasal deformity were included in the study.
      Forty patients with wide nasal dorsum and a prominent hump underwent
      septorhinoplasty with lateral osteotomy (group 1), and 35 patients with a narrow
      nasal dorsum and a minimal hump underwent septorhinoplasty without osteotomy
      (group 2). A Nasal Obstruction Symptom Evaluation (NOSE) questionnaire was used
      to evaluate disease-specific quality of life for patients in both groups. Basic
      characteristics, operative parameters, and preoperative and postoperative NOSE
      scores were compared between the groups. RESULTS: Demographic properties of the
      groups were similar. Intraoperative parameters and postoperative complications
      were not different between the groups, with the exception of operation time
      (which was significantly longer in group 1) and ecchymosis (which was seen in
      whole cases of group 1 and none of the group 2). Preoperative NOSE scores were
      similar in both groups. Postoperative NOSE scores were 5 (0-45) in group 1 and 10
      (0-45) in group 2 (P > 0.05). The NOSE scores were significantly decreased after
      the operation in both groups (P < 0.001). The 2 groups were not significantly
      different when comparing the change in preoperative and postoperative NOSE
      scores. CONCLUSIONS: Rhinoplasty with or without osteotomy is an effective
      treatment for alleviating nasal obstruction symptoms. Osteotomy is an integral
      but not obligatory part of the operation. The addition of the osteotomy procedure
      in selected cases prolonged the operation time and significantly enhanced patient
      satisfaction.

PMID- 24911601
TI  - Giant paranasal sinus osteomas: surgical treatment options.
AB  - Giant paranasal sinus osteomas are rare tumors that may be very closely adherent
      to surrounding anatomical structures, and complete removal of these tumors may be
      very challenging. We report 6 cases of giant paranasal sinus osteomas that were
      removed completely and discussed their symptoms, diagnostic workup, and our
      surgical approach. We reviewed the patient files of our 6 cases with giant
      paranasal osteomas and summarized their history, symptoms, diagnosis, management,
      and follow-up. Three of our patients underwent endoscopic sinus surgery; the
      other 2 patients underwent open surgical approach (osteoplastic flap procedure
      with bicoronal incision), and 1 patient underwent both endoscopic and open
      approaches, all under general anesthesia. Mean patient age was 42.6 years (range,
      18-54 years). Main symptoms were headache, proptosis, and diplopia. Physical
      examination findings include proptosis and frontal puffiness. Paranasal sinus
      computed tomography revealed larger than 3-cm-diameter tumors in the frontal and
      ethmoid sinuses. The surgical approach to each case was customized to the
      location, size, and presenting symptoms of the osteoma. Histopathology revealed
      osteoma in all cases. All patients were evaluated with paranasal sinus computed
      tomography scan postoperatively. At a mean follow-up of 15 months, complication
      was observed in 1 patient; no residual tumor or recurrence was detected following
      surgery. In symptomatic cases with huge tumors, open, endoscopic, or combined
      approaches could be applied because of the location and size of the tumor with
      successful outcomes. Both endoscopic and open approaches are safe and effective
      methods for removal of these tumors. 

PMID- 24911602
TI  - The drop-down technique as an optimal technique for back-wall end-to-side
      anastomosis.
AB  - An advantage of end-to-side anastomosis is that thrombogenesis in the anastomotic
      part is less likely than with end-to-end anastomosis. Conversely, the operative
      procedure for end-to-side anastomosis is more complicated than that of end-to-end
      anastomosis. We usually perform a modified back-wall technique in which the
      outflow vessel is dropped over the inflow vessel. We performed end-to-side
      anastomoses using the single-knot, back-wall, and drop-down techniques and
      compared the time required. In addition, the authors tried to perform
      microvascular anastomosis in 15 clinical cases using the drop-down technique. We
      were able to perform anastomoses quickly using the drop-down, back-wall, and
      single-knot techniques. The drop-down technique was possible in 12 cases of
      venous anastomosis in 15 head and neck reconstruction cases. Using this method,
      we can perform a continuous suture of the posterior wall easily and quickly. The
      drop-down technique can simplify continuous suturing of posterior wall in the
      same way as skin suturing. 

PMID- 24911603
TI  - Safe surgical access to the mandibular nerve at the infratemporal fossae.
AB  - Some anatomic patterns formed by the anterior border of the ascending ramus
      relative to the mandibular canal can cause nerve complications during surgery. We
      determined the frequency of obstructive anatomy in patients undergoing jaw
      surgery, and we described a perioperative method for a bilateral sagittal split
      osteotomy that ensured inferior alveolar nerve (IAN) protection. The anatomy of
      the anterior border of the ascending ramus of the mandible was examined on axial
      and cross-sectional cone beam computed tomographic images of 114 consecutive
      patients undergoing bilateral sagittal split osteotomies. The thickness of the
      anterior border of the ascending ramus determined whether the mandibular foramen
      could be visualized (pattern A) or was obscured (pattern B). Patients with
      pattern B anatomy received a perioperative procedure. Direct visualization of the
      mandibular foramen was achieved in 100% of patients with pattern A anatomy. We
      examined 228 anterior borders of the ascending ramus of the mandible relative to
      the mandibular foramen in 114 patients. Pattern A was observed in 146 cases
      (64%); pattern B, in 82 (36%) cases. The use of the nerve hook resulted in no
      injuries to the IAN in all cases. The described procedure ensured direct
      visualization of the IAN, which prevented inadvertent damage to the IAN during
      instrumentation and surgical procedures at the mandibular foramen.

PMID- 24911604
TI  - Septal cartilage plug technique in spontaneous cerebrospinal fluid rhinorrhea
      postoperatively diagnosed with partial empty sella syndrome.
AB  - The otolaryngologist should consider empty sella syndrome for diagnostic guidance
      when evaluating patients with nontraumatic spontaneous cerebrospinal fluid (CSF)
      rhinorrhea. The radiographic finding of empty sella is frequently reported in
      patients with benign intracranial hypertension (BIH). Patients who have a
      spontaneous CSF leak in the absence of florid symptoms of BIH may have a
      disrupted pattern of CSF flow, and because they are actively leaking CSF before
      surgical repair, they may be at risk for developing elevated intracranial
      pressure and BIH after the CSF leaks have been successfully closed. We describe a
      patient with CSF rhinorrhea who developed headache, papilledema, and visual
      disturbance after surgical repair of the CSF leak. The leak was repaired by the
      placement of a septal cartilage plug with a free mucosal suture graft. This
      technique provides fundamental biomechanical stability, reduces the complexity of
      the multilayer packing method, and promotes an effective seal. 

PMID- 24911605
TI  - Beneficial effects of turnover orbicularis oculi muscle suspension flap for
      treating facial fractures via subciliary incision.
AB  - In patients with moderate lower lid laxity, the lower orbicularis oculi muscle
      becomes atonic or ptotic. Hence, in such patient populations, with periorbital
      fractures, additional vertical support endorsement either by lateral canthopexy
      or orbicularis oculi muscle suspension flap must accompany plate and screw
      fixations. In this report, we shared our experience in applying prophylactic
      suspension to the lower lid with turnover orbicularis oculi transposition muscle
      flap in zygomatic fractures treated by subciliary approach in 98 patients. Our
      results show that turnover orbicularis oculi muscle suspension flap avoids the
      rounding of the lateral canthal angle more successfully and prevents ectropion
      better than the resuspension orbicularis oculi muscle flap does. We advocate
      using this flap where zygomatic fractures are approached via the subciliary
      incision. We foresee that it is a reliable and easily executed technique
      especially in middle-aged patients with moderate lower lid laxity for the
      prevention of ectropion. 

PMID- 24911606
TI  - Transoral robotic supraglottic partial laryngectomy.
AB  - OBJECTIVE: Transoral robotic supraglottic laryngectomy is a new surgical way to
      perform endolaryngeal resection of supraglottic laryngeal carcinoma. The aim of
      this report was to present our initial experience about transoral robotic
      supraglottic laryngectomy for early supraglottic cancer. METHODS: Subjects with
      early squamous cell carcinoma (T1-T2) of supraglottic region who managed using
      transoral robotic surgery in a tertiary referral center were included in the
      study. The technique of robot-assisted resection, intraoperative blood loss, mean
      robotic operating time, pathologic margin status, postoperative extubation, need
      for a tracheotomy, and length of hospitalization, complications, duration of oral
      nutrition, and neck dissection and radiotherapy needs were evaluated. RESULTS:
      Thirteen subjects (12 men, 1 woman) with T1-T2 supraglottic carcinoma were
      successfully operated on with transoral robotic surgery. In all subjects,
      negative margins were obtained. The mean total robotic surgery time was 31.6 (SD,
      16.2) minutes (range, 20-80 minutes). Mean total blood loss was less than 40 mL.
      Subjects started oral nutrition with a mean of 10.8 (SD, 8.9) days (range, 4-30
      days) postoperatively. The mean hospitalization was 15.4 (SD, 10.4) days (range,
      7-42 days). CONCLUSIONS AND RELEVANCE: Transoral robotic supraglottic
      laryngectomy with the da Vinci robotic system can be regarded as a feasible,
      safe, and effective technique. Although short-term results seem discouraging,
      long-term results are needed to evaluate the oncologic safety.

PMID- 24911607
TI  - Zygomatic arch fracture: a new classification and treatment algorithm with
      epidemiologic analysis.
AB  - Determining the optimal method for zygoma fracture reduction is a common
      challenge. Numerous methods for treating zygomatic arch fractures have been
      suggested. However, a substantial gap exists between suggested treatment
      strategies and real-world practice. A general consensus of classification and
      treatment guidelines for zygomatic arch reduction has not yet been established.
      We reviewed our cases and propose a new classification of zygomatic arch fracture
      and a treatment algorithm for successful reduction based on the injury vectors. 

PMID- 24911608
TI  - Comparison of carotid artery endarterectomy and carotid artery stenting in
      patients with atherosclerotic carotid stenosis.
AB  - BACKGROUND: The choice of carotid artery endarterectomy (CEA) or carotid artery
      stenting (CAS), as surgical and interventional treatment of atherosclerotic
      carotid stenosis, respectively, has been controversial in decades, especially for
      asymptomatic patients with carotid stenosis. Age and the diameter of impaired
      carotid artery might be 2 important factors to decide whether CEA or CAS should
      be performed. Besides, contrast-enhanced ultrasound (CEUS) has been confirmed as
      an effective method to predict the risk of stroke by classifying the carotid
      plaque into 4 grades. The role of CEUS in the choice of CEA or CAS still remains
      unclear. METHODS: A retrospective analysis of 38 patients who underwent CEA with
      primary closure and 36 patients who underwent CAS in our hospital from October
      2008 to January 2013 is conducted. Preoperative CEUS was performed to all
      patients, and data were collected and analyzed. All CEAs were performed with
      transverse incision. RESULTS: The hospital stay was longer for the endarterectomy
      group than the stenting group (15.39 versus 10.91 d, P < 0.001), with an
      approximately two-third reduction of hospital costs (Y23686.21 versus Y60855.34,
      P < 0.001). The overall incidence of perioperative complications in the
      endarterectomy group was 7.9%, with no statistically significant difference in
      the group with internal carotid artery greater than or equal to 5 mm and in the
      group with internal carotid artery less than 5 mm (9.1% versus 6.3%, P = 0.75).
      No restenosis occurred in either of the subgroups during the follow-up. In
      patients older than 70 years, the perioperative complications were 0% in CEA and
      10.53% in CAS (P = 0.42); the long-term restenosis was 0% in CEA and 5.26% in CAS
      (P = 0.67). In patients younger than 70 years, the perioperative complications
      were 11.5% in CEA and 23.53% in CAS (P = 0.31); the long-term restenosis was 0%
      in CEA and 0% in CAS (P > 0.01). For patients with grade 4 plaque in CEUS, the
      incidence of adverse events in the CAS group was significantly higher than that
      in the CEA group (7.14% versus 55.56%, P < 0.05). CONCLUSIONS: There were no
      significant differences in perioperative complications or restenosis rate between
      the CAS group and the CEA group in this study. Neither the diameter of impaired
      carotid artery or age could be considered as an indication of applying CEA or
      CAS. However, CEUS might be used as a perioperative assessment method to decide
      whether CEA or CAS should be performed to different patients. The higher the
      grade of plaque enhancement, the higher the risk of adverse events and restenosis
      for CAS might occur.

PMID- 24911609
TI  - The application and progress of high-density porous polyethylene in the repair of
      orbital wall defect.
AB  - High-density porous polyethylene is a type of polymeric biomaterial. When used to
      efficiently fill the extensive orbital volume and correct enophthalmos caused by
      orbital wall defect, it has a significant advantage of biocompatibility, which
      results in a low rate of postoperative exposure and infection. The major
      disadvantage of this material is its radiolucency. However, with the development
      of imaging techniques, it is now possible to use multidetector computed
      tomography to directly contour the implant and describe its position. The use of
      tissue engineering involving high-density porous polyethylene will further
      improve its biocompatibility. At the same time, composite materials will play an
      important role in the repair of orbital wall defect. 

PMID- 24911611
TI  - Autism: moving toward an innovation and investment mindset.

PMID- 24911610
TI  - microRNA expression in peripheral blood cells following acute ischemic stroke and
      their predicted gene targets.
AB  - BACKGROUND: microRNA (miRNA) are important regulators of gene expression. In
      patients with ischemic stroke we have previously shown that differences in immune
      cell gene expression are present. In this study we sought to determine the miRNA
      that are differentially expressed in peripheral blood cells of patients with
      acute ischemic stroke and thus may regulate immune cell gene expression. METHODS:
      miRNA from peripheral blood cells of forty-eight patients with ischemic stroke
      and vascular risk factor controls were compared. Differentially expressed miRNA
      in patients with ischemic stroke were determined by microarray with qRT-PCR
      confirmation. The gene targets and pathways associated with ischemic stroke that
      may be regulated by the identified miRNA were characterized. RESULTS: In patients
      with acute ischemic stroke, miR-122, miR-148a, let-7i, miR-19a, miR-320d, miR
      4429 were decreased and miR-363, miR-487b were increased compared to vascular
      risk factor controls. These miRNA are predicted to regulate several genes in
      pathways previously identified by gene expression analyses, including toll-like
      receptor signaling, NF-kappabeta signaling, leukocyte extravasation signaling,
      and the prothrombin activation pathway. CONCLUSIONS: Several miRNA are
      differentially expressed in blood cells of patients with acute ischemic stroke.
      These miRNA may regulate leukocyte gene expression in ischemic stroke including
      pathways involved in immune activation, leukocyte extravasation and thrombosis.

PMID- 24911612
TI  - Exploring the many facets of research in late-life issues.

PMID- 24911613
TI  - IndividualizedPath: identifying genetic alterations contributing to the
      dysfunctional pathways in glioblastoma individuals.
AB  - Due to the extensive complexity and high genetic heterogeneity of genetic
      alterations in cancer, comprehensively depicting the molecular mechanisms of
      cancer remains difficult. Characterizing personalized pathogenesis in cancer
      individuals can help to reveal new details of the complex mechanisms. In this
      study, we proposed an integrative method called IndividualizedPath to identify
      genetic alterations and their downstream risk pathways from the perspective of
      individuals through combining the DNA copy number, gene expression data and
      topological structures of biological pathways. By applying the method to TCGA
      glioblastoma multiforme (GBM) samples, we identified 394 gene-pathway pairs in
      252 GBM individuals. We found that genes with copy number alterations showed high
      heterogeneity across GBM individuals, whereas they affected relatively consistent
      biological pathways. A global landscape of gene-pathway pairs showed that EGFR
      linked with multiple cancer-related biological pathways confers the highest risk
      of GBM. GBM individuals with MET-pathway pairs showed significantly shorter
      survival times than those with only MET amplification. Importantly, we found that
      the same risk pathways were affected by different genes in distinct groups of GBM
      individuals with a significant pattern of mutual exclusivity. Similarly, GBM
      subtype analysis revealed some subtype-specific gene-pathway pairs. In addition,
      we found that some rare copy number alterations had a large effect on
      contribution to numerous cancer-related pathways. In summary, our method offers
      the possibility to identify personalized cancer mechanisms, which can be applied
      to other types of cancer through the web server
      (http://bioinfo.hrbmu.edu.cn/IndividualizedPath/).

PMID- 24911614
TI  - Radical-induced Cis-Trans isomerization of fatty acids: a theoretical study.
AB  - Trans fatty acids (TFAs) create deleterious effects; thus their existence in
      humans is a great health concern. TFAs can be obtained through diet, or they can
      be formed endogenously by radical-induced cis to trans isomerization. The
      mechanism of isomerization of fatty acid catalyzed by radicals including nitrogen
      dioxide (NO2(*)), thiyl (RS(*)), and peroxide (ROO(*)) radicals were investigated
      using density functional theory. With linoleic acid, a fatty acid consisting of
      two homoconjugated C?C bonds, we found that the radical addition mechanism is
      more favorable than the hydrogen abstraction mechanism. For all investigated
      radicals, the isomerization catalyzed by RS(*) radical involves the smallest
      reaction barrier. We found that NO2(*) reactions through the N-terminus are more
      favorable than reactions through the O-terminus. The reaction barriers for NO2(*)
      catalyzed isomerizations were found to be lowered to a larger extent in polar
      solvent. beta-carotene and lycopene were shown to protect fatty acids from
      isomerization by intercepting the isomerization-causing radicals. 

PMID- 24911615
TI  - Stenting for ST-segment elevation myocardial infarction is associated with less
      neointimal hyperplasia in the pooled IVUS analysis from HORIZONS-AMI and the
      TAXUS IV and V and ATLAS workhorse, long lesion, and direct stent studies.
AB  - OBJECTIVE: To investigate the difference in neointimal hyperplasia (NIH) between
      ST-segment elevation myocardial infarction (STEMI), stable angina pectoris (SAP),
      and unstable angina pectoris (UAP). PATIENTS AND METHODS: From formal core
      laboratory intravascular ultrasound substudies, we compared NIH after paclitaxel
      eluting stents (PES) or bare metal stents (BMS) in STEMI lesions from HORIZONS
      AMI trial with SAP and UAP lesions from TAXUS IV, V, and ATLAS studies. RESULTS:
      At follow-up, %NIH at the minimum lumen area (MLA) site was less in STEMI (n=212)
      than in UAP (n=233) and SAP (n=440) lesions treated with PES (19.6 vs. 26.2 vs.
      25.0%, P=0.002; all intravascular ultrasound data shown as least-square means in
      abstract) and less in STEMI (n=66) than in UAP (n=72) and SAP (n=143) lesions
      treated with BMS (34.0 vs. 26.7 vs. 45.5%, P=0.0003). As a result, MLA at follow
      up was larger in STEMI than in UAP and SAP lesions treated with PES (5.9 vs. 5.2
      vs. 5.0 mm, P<0.0001) or treated with BMS (5.1 vs. 4.3 vs. 4.0 mm, P=0.002). Net
      volume obstruction ([NIH/stent volume]*100) at follow-up was significantly less
      in STEMI than in UAP and SAP lesions treated with PES (7.8 vs. 13.4 vs. 13.4%,
      P<0.0001) or BMS (20.6 vs. 28.5 vs. 32.1%, P<0.0001). Multivariate linear
      regression analysis showed that STEMI was correlated independently and inversely
      with net volume obstruction compared with SAP (regression coefficient -6.99,
      P<0.0001) or UAP (regression coefficient -6.29, P<0.0001). CONCLUSION:
      Implantation of PES or BMS in STEMI compared with UAP and SAP was associated with
      less NIH.

PMID- 24911616
TI  - Is eating science or common sense? Knowledge about "natural foods" among self
      identified "natural food" consumers, vendors and producers in rural and urban
      Mexico.
AB  - OBJECTIVE: To explore the common sense knowledge that consumers, vendors and
      producers hold of "natural foods". The focus was on common knowledge because this
      is infrequently explored in social psychology where most studies focus on the
      implementation of scientific knowledge. The focus was on natural foods because
      the naturalness of foods seems to be one of the particular concerns that current
      consumers have about today's food market and because a specific natural food
      preference was observed in the contexts of study. METHOD: Fifty-seven informants
      in a rural context and 58 informants in an urban context participated in either a
      free association study or an interview study. Data content were analyzed.
      RESULTS: In the urban context natural foods obtain their significance in the
      relationship between food and the self-concept; eating natural (or good) food is
      a task that requires effort and attitude, and foods obtain a moral value. In the
      rural context natural foods obtain their significance as an expression of a
      social and cultural system of interdependence that establishes practices and
      customs that have a long history in the community. CONCLUSIONS: It is suggested
      that these common knowledge systems are related to practical challenges that are
      particular to the informants' context and that the structure of their common
      sense knowledge systems depend on the mediation of the flow of scientific
      knowledge and technological knowledge in each context.

PMID- 24911617
TI  - Salt taste sensitivity thresholds in adolescents: are there any relationships
      with body composition and blood pressure levels?
AB  - The aim of this study was to identify the salt taste sensitivity thresholds and
      relationships with body composition and blood pressure levels in a cross
      sectional study of adolescents. Blood pressure and body composition were measured
      with a digital device and by anthropometry, respectively. The salt taste
      sensitivity threshold was measured with 9 solutions with different sodium
      chloride concentrations to assess the sensitivity to saltiness. The solutions (4,
      8, 15, 30, 60, 120, 250, 500 and 1000 mmol/L sodium chloride) were served in
      increasing concentrations until the taste was correctly identified. The taste
      sensitivity threshold was then classified as normal or high. In total, 421
      adolescents (55.6% female), with an average age of 15.8 +/- 0.91 years, were
      evaluated. The median threshold was 30 mmol/L, and 36.1% had a high threshold.
      The high blood pressure prevalence was 12.6%, and 25.5% of the subjects were
      overweight. When the mean systolic and diastolic blood pressure levels were
      compared between the normal and increased threshold groups after adjusting for
      gender, age, sedentary lifestyle and body mass index, only diastolic blood
      pressure showed a statistically significant effect (P < 0.0001) between the
      groups. The effect of a high threshold on body composition after adjusting for
      gender, age and physical inactivity was not significant (P = 0.177). There was no
      relationship between a high threshold and systolic pressure or body composition
      in the evaluated adolescents; therefore, only diastolic blood pressure was
      affected. 

PMID- 24911618
TI  - Appetite and gut peptide responses to exercise and calorie restriction. The
      effect of modest energy deficits.
AB  - Weight loss is the result of a sustained negative energy balance, which is
      typically achieved by decreasing food intake and/or increasing physical activity.
      Current evidence suggests that acute energy deficits of ~4820 kJ elicit
      contrasting homeostatic responses when induced by exercise and food restriction
      but the response to government-recommended energy deficits is unknown. Twelve
      healthy men (mean(SD): age 24(5) years, body mass index 23.8(2.7) kg?m(-2),
      maximum oxygen uptake 55.4(9.1) mL?kg(-1)?min(-1)) completed three 8 h trials
      (control (Con), exercise-induced energy deficit (Ex-Def) and food restriction
      (Food-Def)) separated by 1 week. Thirty minutes of cycling at 64.5(3.2)% of
      maximum oxygen uptake was performed in Ex-Def from 0 to 0.5 h, which induced an
      energy deficit of 1469(256) kJ. An equivalent energy deficit was induced in Food
      Def (1478(275) kJ) by reducing the energy content of standardised test meals at 1
      h and 4 h. Appetite ratings, acylated ghrelin and peptide YY3-36 concentrations
      were measured throughout each trial. An ad libitum meal was provided at 7 h.
      Appetite was higher in Food-Def than Ex-Def from 4 to 8 h (P = 0.033) and tended
      to be higher across the entire 8 h trial (P = 0.059). However, energy intake at
      the ad libitum meal did not differ between trials (P = 0.634; Con 4376 (1634);
      Food-Def 4481 (1846); Ex-Def 4217 (1850) kJ). Acylated ghrelin was not related to
      changes in appetite but plasma PYY3-36 concentrations were higher in Ex-Def than
      Food-Def (P < 0.05) and negatively correlated with changes in appetite across the
      entire 8 h trial (P = 0.037). An energy deficit of ~1475 kJ stimulated
      compensatory increases in appetite when induced via calorie restriction but not
      when achieved by an acute bout of exercise. Appetite responses were associated
      with changes in plasma PYY3-36 but not acylated ghrelin concentrations and did
      not influence subsequent energy intake. 

PMID- 24911619
TI  - Trajectories of dietary change and the social context of migration: a qualitative
      study.
AB  - The aim of this article was to explore the influence of migration on changes in
      dietary practices, relating these changes to the social contexts in which they
      occur. Numerous studies have described how migration from poor countries and
      regions to more developed ones leads migrants to adopt a modern diet associated
      to the risk of acquiring chronic diseases. However, different contexts might
      influence dietary change in migrants in diverse ways. For this purpose, 28 semi
      structured interviews were conducted with adult, female internal migrants to a
      border city in Mexico. The interviews were analyzed using thematic analysis. The
      results showed trajectories of dietary change to be associated to social position
      before and after migration. For the participants from rural areas, migration was
      accompanied by an increase in the consumption of processed foods, and also
      changes in food insecurity. Migrants who came from urban areas reported a
      decrease in the perceived quality of food available to them, but their eating
      pattern was modified only slightly. For some interviewees, migration resulted in
      the possibility to choose what to eat in a more autonomous way. We discuss how
      the effect of migration on dietary changes can be manifold, and the necessity to
      delve into how social context influences these changes. 

PMID- 24911621
TI  - Asymmetric synthesis of functionalized dihydronaphthoquinones containing
      quaternary carbon centers via a metal-free catalytic intramolecular acylcyanation
      of activated alkenes.
AB  - A novel metal-free catalytic annulation was developed through a Lewis base
      catalyzed asymmetric allylic alkylation and the ensuing unprecedented asymmetric
      intramolecular acylcyanation of alkenes. This protocol provides a unique and
      facile access to prepare enantioenriched densely functionalized
      dihydronaphthoquinones accompanied by enantiomerically pure 3,3-disubstituted
      phthalides bearing quaternary carbon centers. 

PMID- 24911620
TI  - Maternal feeding self-efficacy and fruit and vegetable intakes in infants.
      Results from the SAIDI study.
AB  - Adequate consumption of fruits and vegetables (FV) is a characteristic of a
      healthy diet but remains a challenge in nutrition interventions. This cross
      sectional study explored the multi-directional relationships between maternal
      feeding self-efficacy, parenting confidence, child feeding behaviour, exposure to
      new food and FV intake in a cohort of 277 infants. Mothers with healthy infants
      weighing >=2500 g and >=37 weeks gestation were recruited post-natally from 11
      South Australian hospitals. Socio-demographic data were collected at recruitment.
      At 6 months postnatal, infants were weighed and measured, and mothers completed a
      questionnaire exploring their perceptions of child feeding behaviour and child
      exposure to new foods. The questionnaire also included the Short Temperament
      Scale for Infants, Kessler 10 to measure maternal psychological distress and 5
      items measuring maternal feeding self-efficacy. The number of occasions and
      variety of FV (number of subgroups within food groups) consumed by infants were
      estimated from a 24-hour dietary recall and 2 days food record. Structural
      equation modelling was performed using Mplus version 6.11. Median (IQR) variety
      scores were 2 (1-3) for fruit and 3 (2-5) for vegetable intake. The most popular
      FV consumed were apple (n = 108, 45.0%) and pumpkin (n = 143, 56.3%). None of the
      variables studied predicted the variety of child fruit intake. Parenting
      confidence, exposure to new foods and child feeding behaviour were indirectly
      related to child vegetable intake through maternal feeding self-efficacy while
      total number of children negatively predicted child vegetable variety (p < 0.05).
      This highlights the need for addressing antecedents of maternal feeding self
      efficacy and the family eating environment as key strategies towards development
      of healthy eating in children. 

PMID- 24911622
TI  - 'Laboratory talk' in U.S. sociology, 1890-1930: the performance of scientific
      legitimacy.
AB  - This paper examines one aspect of early twentieth century debates over the
      meaning of scientific methodology and epistemology within the social sciences:
      the tendency of sociologists to invoke "laboratory" as a multivalent concept and
      in reference to diverse institutions and sites of exploration. The aspiration to
      designate or create laboratories as spaces of sociological knowledge production
      was broadly unifying in early American sociology (1890-1930), even though there
      was no general agreement about what "laboratory" meant, nor any explicit
      acknowledgment of that lack of consensus. The persistence of laboratory talk in
      sociology over decades reflects the power of "laboratory" as a productively
      ambiguous, legitimizing ideal for sociologists aspiring to make their discipline
      rigorously scientific. 

PMID- 24911623
TI  - First principles optical spectra of the beta-SiC(0 0 1)/Al interface.
AB  - The optical spectra of the beta-SiC(0 0 1)/Al interface has been studied using
      first principles time-dependent density functional theory. We considered the bare
      random phase approximation as well as two different exchange-correlation kernels,
      i.e. the adiabatic-local-density-approximation and the jellium-with-gap kernel of
      Trevisanutto et al (2013 Phys. Rev. B 87 205143). We investigated the C
      terminated interface with Al-C interaction which has quite good bond adhesion
      between the two materials. The absorption spectra of all methods are dependent on
      the electric field polarization, showing high anisotropy in these systems. When
      the electric field is parallel to the interface plane, all methods predict a
      metallic behavior, while enhanced semiconductor excitonic effects are present
      when the electric field is perpendicular to the interface plane. Between the
      considered methods, the jellium-with-gap kernel enhances the excitonic effects of
      the beta-SiC(0 0 1)/Al interface with respect to the other methods.

PMID- 24911624
TI  - Class I ADP-ribosylation factors are involved in enterovirus 71 replication.
AB  - Enterovirus 71 is one of the major causative agents of hand, foot, and mouth
      disease in infants and children. Replication of enterovirus 71 depends on host
      cellular factors. The viral replication complex is formed in novel, cytoplasmic,
      vesicular compartments. It has not been elucidated which cellular pathways are
      hijacked by the virus to create these vesicles. Here, we investigated whether
      proteins associated with the cellular secretory pathway were involved in
      enterovirus 71 replication. We used a loss-of-function assay, based on small
      interfering RNA. We showed that enterovirus 71 RNA replication was dependent on
      the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP
      ribosylation factors 1 and 3, but not three others, inhibited viral replication
      in cells. We also demonstrated with various techniques that the brefeldin-A
      sensitive guanidine nucleotide exchange factor, GBF1, was critically important
      for enterovirus 71 replication. Our results suggested that enterovirus 71
      replication depended on GBF1-mediated activation of Class I ADP-ribosylation
      factors. These results revealed a connection between enterovirus 71 replication
      and the cellular secretory pathway; this pathway may represent a novel target for
      antiviral therapies. 

PMID- 24911625
TI  - Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an
      Australian Caucasian breast cancer cohort.
AB  - Breast cancer is the second most common cancer worldwide and the most common
      cancer reported in women. This malignant tumour is characterised by a number of
      specific features including uncontrolled cell proliferation. It ranks fifth in
      the world as a cause of cancer death overall in developed countries and is the
      second most frequent cause of cancer death in women. Early diagnosis increases 5
      year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex
      proteins composed of a core protein to which a number of highly sulfated side
      chains attach, ubiquitous to the cell surface and within the extracellular
      matrix. HSPG side chains are synthesised by a highly co-ordinated process
      resulting in distinct sulfation patterns, which determine specific interactions
      with cell-signalling partners including growth factors, their receptors, ligands
      and morphogens. The enzymes responsible for chain initiation, elongation and
      sulfation are critical for creating HS chain variability conferring biological
      functionality. This study investigated a single nucleotide polymorphism in SULF1,
      the enzyme responsible for the 6-O desulfation of heparan sulfate side chains. We
      investigated this SNP in an Australian Caucasian case-control breast cancer
      population and found a significant association between SULF1 and breast cancer at
      both the allelic and genotypic levels (allele, p=0.016; genotype, p=0.032). Our
      results suggest that the rs2623047 SNP in SULF1 may impact breast cancer
      susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated
      with an increased risk of developing breast cancer in our cohort. The
      identification of markers including SULF1 may improve detection of this disease
      at its earliest stages improving patient treatment and prognosis. 

PMID- 24911626
TI  - De novo sequencing and transcriptome analysis of Ustilaginoidea virens by using
      Illumina paired-end sequencing and development of simple sequence repeat markers.
AB  - Ustilaginoidea virens is the causal agent of rice false smut, which is a rice
      disease of increasing importance worldwide that has caused with the quantitative
      and qualitative rice losses. However, research on the pathogenic mechanism of U.
      virens is limited. In this study, we reported a de novo assembling, annotation,
      and characterization of the transcriptome and developed simple sequence repeat
      (SSR) markers of U. virens. U. virens transcripts of the mycelia and conidia
      mixture were sequenced using Illumina RNA-seq technology. A total of 52,554,142
      clean reads were assembled into 36,496 transcripts representing 18,534 unigenes.
      Assembled unigenes were annotated through sequence comparison with known protein
      databases, and 48.48% of the unigenes were without hits in any of these
      databases. Clusters of orthologous groups for eukaryotic complete genome analysis
      identified the largest set of genes associated with posttranslational
      modification, protein turnover and chaperones. Kyoto Encyclopedia of Genes and
      Genomes pathway analyses identified the number of genes associated with mitogen
      activated protein kinase and calcium-calcineurin pathways. The study also
      identified several putative pathogenicity determinants and candidate effectors in
      U. virens by using the pathogen-host interaction database. In addition,
      bioinformatics analysis revealed the presence of 12,298 SSR markers. This study
      provides a better understanding of the biology of U. virens and is an excellent
      resource for candidate genes required for pathogenesis discovery. 

PMID- 24911627
TI  - Coinage-metal mediated ring opening of cis-1,2-dimethoxycyclopropane: trends from
      the gold, copper, and silver Fischer carbene bond strength.
AB  - N-heterocyclic carbene (NHC) supported coinage metal cations proved to react in
      the gas phase with the electron-rich cis-1,2-dimethoxycyclopropane. Upon
      Collision Induced Dissociation (CID), several spectrometric fragment-ion signals
      were observed, one corresponding to the recovery of the bare cation IMes-M(+)
      (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) and the second to the
      methoxymethylidene metal complex IMes-M-[HCOCH3](+). The gold and copper
      complexes appear to stabilize the carbene sufficiently enough to promote the
      latter channel. On the contrary, the silver complex binds weakly to the
      methoxymethylidene moiety as observed by the predominance of the bare cation IMes
      M(+) channel. Density Functional Theory (DFT) investigations of the Potential
      Energy Surface and Bond Energy Decomposition Analyses provided results that
      correlate well with the experimental data. In the case of the bare cation
      channel, two distinct reaction pathways were found: a straightforward
      decoordination of the cyclopropane and a cationic rearrangement of the three
      membered ring into a dimethoxypropylene isomer before dissociation. However, for
      the abstraction of the methoxymethylidene moiety by the metal cation, only one
      pathway was found. In analogy to earlier studies by other groups, we found the
      trend Au > Cu > Ag for the metal-carbene bond strength. 

PMID- 24911628
TI  - Sharp transition in the immunoimmobilization of E. coli O157:H7.
AB  - This work focuses on immobilization of living enterohemorrhagic Escherichia coli
      O157:H7 on a gold surface as a function of the concentration of antibody tethered
      to the surface in the physiological environment of the organisms. Experiments are
      conducted using antibodies raised against bacterial surface lipopolysaccharides
      (LPS) tethered to gold-coated silicon wafers at surface concentrations spanning a
      range from submonolayers of antibodies to full coverage, an estimated 1 antibody
      per ~100 nm(2). A careful optimization of surface chemistry is conducted to
      obtain the most efficient tethering of the antibodies to the surface. The
      mechanism of immobilizing the bacteria is antibody-antigen interactions between
      the tethered antibodies on the surface and the bacterial surface LPS firmly
      attached to the bacteria. This type of attachment is known as
      immunoimmobilization. The experiments suggest no noticeable bacterial attachment
      until the surface antibody concentration reaches ~70% of a full monolayer of
      coverage. Above this critical antibody density, a sharp increase in
      immunoimmobilized bacteria is observed as they populate nearly 80% to 100% of the
      available surface area, reaching ~1.2 cells/10 MUm(2). This sharp increase in
      population is tentatively explained in terms of the minimum number of antibody
      antigen interactions required per bacterium to immobilize the cell. This critical
      number is estimated to be ~6000-8000 antibodies per bacterium (having a 1 MUm(2)
      footprint on the surface) under the assumption that a full monolayer of
      antibodies is about 1 antibody per ~100 nm(2). However, the large majority of the
      6000-8000 antibodies are not expected to participate in antibody-antigen
      interactions, in that the loose LPS in solution will saturate many of these
      antibodies before bacteria have a chance to interact with them. Furthermore, the
      geometric considerations will further restrict the majority of the active
      antibodies from interacting with the surface antigens of the cell, reducing its
      effective contact area with the antibodies considerably. 

PMID- 24911629
TI  - Phase transitions and interface phenomena in the cryogenic temperature domain of
      a niobate nanostructured ceramic.
AB  - Powder neutron diffraction and dielectric spectroscopy were used to investigate
      both crystallographic and dielectric permittivity properties of a Sr2KNb5O15
      single phase ferroelectric oxide with nanosized grains ranging from 35 nm to 90
      nm. Measurements were carried out in the temperature range from 10 K (cryogenic)
      to 550 K. All neutron diffraction data were indexed on the basis of a tetragonal
      double unit cell. From 10 K to room temperature the space group of the Sr2KNb5O15
      ferroelectric phase was considered to be P4bm. The refinement of the paraelectric
      phase (at 550 K) was determined in the centrosymmetric space group P4/mbm.
      Dielectric spectroscopy measurements were performed in a thermal cycle. A set of
      four phase transitions non-related to symmetry changing was detected from
      Rietveld analysis of neutron powder diffraction data. During a thermal cycle, in
      the cryogenic temperature domain, strong thermal hysteresis is developed. Both
      phase transition and thermal hysteresis were correlated. These phenomena are
      associated with Nb-cation atomic displacements in the NbO6 octahedra along the c
      axis direction and of the domain with different frequencies involving grains as
      well as an excess of interfaces ascribed to the grain boundary. The bulk/grain
      boundary interfaces in nanostructured ceramics are correlated with the thermal
      stability phenomenon. 

PMID- 24911630
TI  - Outdoor particulate matter exposure and lung cancer: a systematic review and meta
      analysis.
AB  - BACKGROUND: Particulate matter (PM) in outdoor air pollution was recently
      designated a Group I carcinogen by the International Agency for Research on
      Cancer (IARC). This determination was based on the evidence regarding the
      relationship of PM2.5 and PM10 to lung cancer risk; however, the IARC evaluation
      did not include a quantitative summary of the evidence. OBJECTIVE: Our goal was
      to provide a systematic review and quantitative summary of the evidence regarding
      the relationship between PM and lung cancer. METHODS: We conducted meta-analyses
      of studies examining the relationship of exposure to PM2.5 and PM10 with lung
      cancer incidence and mortality. In total, 18 studies met our inclusion criteria
      and provided the information necessary to estimate the change in lung cancer risk
      per 10-MUg/m3 increase in exposure to PM. We used random-effects analyses to
      allow between-study variability to contribute to meta-estimates. RESULTS: The
      meta-relative risk for lung cancer associated with PM2.5 was 1.09 (95% CI: 1.04,
      1.14). The meta-relative risk of lung cancer associated with PM10 was similar,
      but less precise: 1.08 (95% CI: 1.00, 1.17). Estimates were robust to restriction
      to studies that considered potential confounders, as well as subanalyses by
      exposure assessment method. Analyses by smoking status showed that lung cancer
      risk associated with PM2.5 was greatest for former smokers [1.44 (95% CI: 1.04,
      1.22)], followed by never-smokers [1.18 (95% CI: 1.00, 1.39)], and then current
      smokers [1.06 (95% CI: 0.97, 1.15)]. In addition, meta-estimates for
      adenocarcinoma associated with PM2.5 and PM10 were 1.40 (95% CI: 1.07, 1.83) and
      1.29 (95% CI: 1.02, 1.63), respectively. CONCLUSION: The results of these
      analyses, and the decision of the IARC Working Group to classify PM and outdoor
      air pollution as carcinogenic (Group 1), further justify efforts to reduce
      exposures to air pollutants that can arise from many sources.

PMID- 24911631
TI  - A statistical model for estimation of fish density including correlation in size,
      space, time and between species from research survey data.
AB  - Trawl survey data with high spatial and seasonal coverage were analysed using a
      variant of the Log Gaussian Cox Process (LGCP) statistical model to estimate
      unbiased relative fish densities. The model estimates correlations between
      observations according to time, space, and fish size and includes zero
      observations and over-dispersion. The model utilises the fact the correlation
      between numbers of fish caught increases when the distance in space and time
      between the fish decreases, and the correlation between size groups in a haul
      increases when the difference in size decreases. Here the model is extended in
      two ways. Instead of assuming a natural scale size correlation, the model is
      further developed to allow for a transformed length scale. Furthermore, in the
      present application, the spatial- and size-dependent correlation between species
      was included. For cod (Gadus morhua) and whiting (Merlangius merlangus), a common
      structured size correlation was fitted, and a separable structure between the
      time and space-size correlation was found for each species, whereas more complex
      structures were required to describe the correlation between species (and space
      size). The within-species time correlation is strong, whereas the correlations
      between the species are weaker over time but strong within the year. 

PMID- 24911632
TI  - Comparative ectoparasite loads of five seabird species in the Galapagos Islands.
AB  - In this paper we describe the ectoparasitic lice (Insecta: Phthiraptera) found on
      5 species of seabirds (magnificent frigatebird Fregata magnificens; great
      frigatebird Fregata minor ; Nazca booby Sula granti ; blue-footed booby Sula
      nebouxii ; and red-footed booby Sula sula ) on the Galapagos Archipelago. We
      found 9 species of ectoparasitic lice: 5 species of Pectinopygus ischnocerans, 1
      infesting each host; 2 species of Colpocephalum amblyceran lice, 1 on each
      frigatebird species; and 2 shared amblycerans, Eidmanniella albescens (Piaget,
      1880) found on Nazca and blue-footed boobies and Fregatiella aurifasciata
      (Kellogg, 1899) found on the 2 frigatebirds. We tested the relative importance
      and interactions of host sex, body size, host, island, host family, and breeding
      status and found that inter-island differences were the main predictors of
      prevalence and infestation intensity. These differences could be related to host
      density or weather, but further evidence is needed. 

PMID- 24911633
TI  - Objectively measured physical activity, sedentary time and sleep duration:
      independent and combined associations with adiposity in canadian children.
AB  - OBJECTIVE: To examine independent and combined associations among objectively
      measured movement/non-movement behaviors (moderate-to-vigorous-intensity physical
      activity (MVPA), total sedentary time and sleep duration) and adiposity
      indicators in a sample of Canadian children. METHODS: A cross-sectional study was
      conducted on 507 children aged 9-11 years from Ottawa, Canada. Movement/non
      movement behaviors were assessed using an Actigraph GT3X+ accelerometer over 7
      days (24-h protocol). Outcomes included percentage body fat (bioelectrical
      impedance) and waist-to-height ratio. RESULTS: After adjustment for age, sex,
      ethnicity, maturity offset, fast food consumption, annual household income and
      highest level of parental education, MVPA was inversely and sedentary time
      positively associated with adiposity indicators, whereas sleep duration was not.
      However, only MVPA remained significantly associated with adiposity indicators
      after additional adjustment for the other movement/non-movement behaviors.
      Combined associations using tertiles of the three movement/non-movement behaviors
      showed that higher levels of MVPA were associated with lower adiposity
      indicators, irrespective of total sedentary time and sleep duration. CONCLUSIONS:
      Higher levels of MVPA were associated with lower adiposity in this sample of
      children regardless of sedentary time and sleep duration. Although correlational
      in nature, these findings suggest that future efforts of obesity reduction should
      focus more on increasing MVPA than on reducing sedentary time or increasing sleep
      duration to maximize the effectiveness of interventions.

PMID- 24911634
TI  - Ox-LDL induces endothelial cell apoptosis via the LOX-1-dependent endoplasmic
      reticulum stress pathway.
AB  - OBJECTIVE: To investigate the effect of lectin-like ox-LDL receptor-1 (LOX-1) on
      oxidized low-density lipoprotein (ox-LDL)-induced apoptosis and the involvement
      of the endoplasmic reticulum (ER) stress response pathway. METHODS AND RESULTS:
      Human umbilical vein endothelial cells were treated with 50, 100, or 200 MUg/ml
      ox-LDL and cultured for 12, 24, or 48 h for concentration- and time-dependent
      studies. Cells were transfected with LOX-1 or Nox-4 shRNAs, and target proteins
      were inhibited with the corresponding antibodies for mechanistic studies. Active
      proteins and mRNAs were analyzed by Western blotting and RT-PCR, respectively.
      Cell apoptosis was analyzed by Annexin and Hoechst staining assays. Ox-LDL
      induced both apoptosis and protein expression of LOX-1 and Nox-4 through
      activation of ER stress sensors IRE1 and PERK, and nuclear translocation of ATF6
      and their subsequent pathways were indicated by JNK, eukaryotic initiation factor
      2 phosphorylation, XBP-1, and chaperone GRP78 expression; up-regulation of
      proapoptotic proteins CHOP and Bcl-2; and caspase-12 activity. LOX-1 gene
      silencing and treatment with an anti-LOX-1 antibody attenuated the effects of ox
      LDL. Pretreatment with irestatin 9389, salubrinal, or AEBSF also blocked ox-LDL
      induced expression of CHOP and Bcl-2 and activation of caspase-12 activity,
      leading to an attenuation of endothelial cell apoptosis. Furthermore, Nox-4 siRNA
      attenuated the up-regulated expression of GRP78, PERK, IRE1, and XBP-1 to reduce
      ox-LDL-induced endothelial cell apoptosis. CONCLUSIONS: LOX-1 plays a critical
      role in ox-LDL-induced endothelial cell apoptosis via the ER stress pathway.

PMID- 24911636
TI  - Circulating irisin levels are positively associated with endothelium-dependent
      vasodilation in newly diagnosed type 2 diabetic patients without clinical
      angiopathy.
AB  - OBJECTIVE: Irisin is a newly identified myokine that can promote energy
      expenditure and alleviate insulin-resistance in animal model. It has been
      established that insulin resistance is frequently associated with endothelial
      dysfunction. Therefore, we hypothesize that circulating irisin levels are
      associated with endothelial dysfunction in type 2 diabetes. METHODS: One hundred
      and eighty eight patients with newly diagnosed type 2 diabetes and 40 healthy
      subjects were recruited. Serum irisin concentrations were measured by using
      enzyme-linked immunosorbent assay, and flow-mediated dilation (FMD) was evaluated
      by using high-resolution ultrasound. RESULTS: The mean value of circulating
      irisin levels in newly diagnosed type 2 diabetes was 13.25 ng/ml, which was
      significantly lower than that in controls (25.98 ng/ml, p < 0.001). By dividing
      the distribution of FMD levels into quartiles, serum irisin levels were increased
      gradually with the increase of FMD levels (p < 0.001). Multivariate stepwise
      regression analysis demonstrated that serum irisin levels were independently
      associated with FMD (p = 0.009). By logistic regression analysis the odds ratio
      for lower FMD levels was reduced by 11.8% per 1 ng/ml increase in serum irisin
      concentration after adjustment for multivariate metabolic factors [OR (95% CI);
      0.882 (0.709-0.969)]. CONCLUSION: These results demonstrated that circulating
      irisin levels were decreased in newly diagnosed Chinese type 2 diabetic patients
      without clinical angiopathy and positively associated with FMD levels.

PMID- 24911635
TI  - The cardioprotective effect of sodium tanshinone IIA sulfonate and the optimizing
      of therapeutic time window in myocardial ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: The protective effect of sodium tanshinone IIA sulfonate (STS)
      pretreatment against experimental myocardial ischemia/reperfusion (I/R) has been
      demonstrated previously, however its therapeutic effects and mechanism of action
      still remain unclear. The objective of this study was to investigate the
      therapeutic time window and potential mechanism of STS action on myocardial I/R
      injury in a rat model of myocardial I/R. METHODS: Rats received 30 min ischemia
      by complete ligation of the left ascending coronary artery, and then were
      reperfused for 24 h. STS (8 mg/kg) was administered intravenously 15 min before
      and at 0, 0.5, 1, 2, 4, 6 h after reperfusion. The infarct size and several
      consequences of myocardial I/R including myocardial zymogram, antioxidant status,
      cardiac function and microstructure disorder were evaluated 24 h after
      reperfusion. Furthermore, the effect of STS on heme oxygenase-1 (HO-1) protein
      expression and nuclear factor-kappaB (NF-kappaB) activation were also evaluated.
      RESULTS: In the present study, the time point of optimal cardioprotective effect
      of STS was within 2 h after reperfusion, with declining effect at 4 h and no
      effect at 6 h after the onset of reperfusion. In addition, STS-mediated
      cytoprotection against oxidative stress and inflammatory responses was correlated
      with an increased HO-1 activity.. CONCLUSIONS: STS could ameliorate cardiac
      dysfunction and variation of myocardial zymogram, up-regulate antioxidant
      systems. Moreover, modulation of HO-1 was involved in STS induced
      cardioprotection..

PMID- 24911637
TI  - A decrease in total bilirubin predicted hyper-LDL cholesterolemia in a health
      screening population.
AB  - OBJECTIVE: To investigate cross-sectional and longitudinal associations between
      serum total bilirubin (TB) and LDL cholesterol. METHODS: It is a retrospective
      observational study. Cross-sectional and longitudinal associations between TB and
      hyper-LDL cholesterolemia were investigated in a health screening population.
      Odds ratios (ORs) of coexisting hyper-LDL cholesterolemia for TB were calculated
      in 3,866 subjects, Spearman's correlation coefficients between baseline TB and
      LDL cholesterol at baseline and after 4 years were calculated in 1,735 subjects
      who did not use antihyperlipidemic drugs and hazard ratios (HRs) of incident
      hyper-LDL cholesterolemia for TB were calculated in 1,992 followed subjects.
      RESULTS: The ORs (p values) of coexisting hyper-LDL cholesterolemia for each 1 SD
      increase in TB was 1.04 (0.998) adjusted for sex, age, smoking, LDL cholesterol
      and other confounders. Spearman's correlation coefficients (p values) between
      baseline TB and LDL cholesterol at baseline and after 4 years and changes in LDL
      cholesterol were -0.026 (0.271), -0.078 (0.001) and -0.062 (0.010), respectively.
      Among 1,992 followed subjects, 481 developed hyper-LDL cholesterolemia during 4
      years (60.4 per 1,000 person-years). The HRs (95% confidence intervals; p values)
      of incident hyper-LDL cholesterolemia for each 1 SD increase in TB was 0.86 (0.77
      0.96; 0.006) adjusted for sex, age, smoking, LDL cholesterol, body mass index,
      triglycerides, HDL cholesterol, fasting glucose and other confounders. The
      quintiles of TB were significantly associated with the incident hyper-LDL
      cholesterolemia adjusted for the above covariates (p for trend = 0.008).
      CONCLUSION: A decrease in TB predicted incident hyper-LDL cholesterolemia in a
      health screening population.

PMID- 24911639
TI  - Time course of atherosclerosis regression.

PMID- 24911640
TI  - Total joint arthroplasty: tips for improving efficiency.
AB  - Total joint arthroplasty is a very successful procedure that alleviates pain in
      arthritic patients. However, our current healthcare delivery system may not be
      able to provide the value of arthroplasty to match the demand in our increasing
      arthritic population. Increasing hospital efficiency and value for patients
      needing total joint replacement will bring this pain-relieving procedure to more
      patients with benefits to surgeons and hospitals. This article reviews segments
      in the knee arthroplasty pathway that will provide efficiency and value when they
      are optimized. 

PMID- 24911638
TI  - Adiponectin attenuates abdominal aortic aneurysm formation in hyperlipidemic
      mice.
AB  - OBJECTIVE: Abdominal aortic aneurysms (AAA) are age-associated, life-threatening
      inflammatory dilations of the abdominal aorta. Human population studies have
      shown an association between obesity and AAA formation, but the molecular
      mechanisms underlying this connection remain largely unexplored. Adiponectin is
      an anti-inflammatory adipokine that is downregulated in obesity. In this study we
      evaluated the role of adiponectin in a model of AAA using apolipoprotein
      E/adiponectin double-knockout (Apoe(-/-)Apn(-/-)) mice. APPROACH AND RESULTS:
      Angiotensin II (Ang II)-infusion in male Apoe(-/-)Apn(-/-) mice led to a higher
      incidence of AAA and a significant increase of maximal aortic diameter compared
      with that of Apoe(-/-) mice (2.12 +/- 0.07 mm vs. 1.67 +/- 0.09 mm, respectively
      at 28 days). Adiponectin deficiency augmented the early infiltration of
      macrophages and increased the expression of pro-inflammatory factors in the
      dilated aortic wall. MMP-2 and MMP-9 activation was also augmented in the aorta
      of Apoe(-/-)Apn(-/-) mice compared to Apoe(-/-) mice. These data suggest that the
      downregulation of adiponectin could directly contribute to the elevated incidence
      of AAA observed in obese individuals. CONCLUSIONS: Adiponectin attenuates Ang II
      induced vascular inflammation and AAA formation in mice.

PMID- 24911641
TI  - The impact patient-specific instrumentation has had on my practice in the last 5
      years.
AB  - I have performed total knee arthroplasty (TKA) using patient- specific
      instrumentation (PSI) (TRUMATCH(r) Personalized Solutions, DePuy Synthes Joint
      Reconstruction, Warsaw, Indiana) since July 2009. Since that time, I have
      performed over 600 of these procedures, all at the same hospital and all using
      the same personnel I worked with before I began using PSI. I do not have a
      physician assistant, but I do have a surgical assistant who scrubs with and
      assists me on all TKAs. There are a number of reasons why a surgeon may decide to
      use PSI. This paper discusses the effect PSI has had on my practice in the last 5
      years, including my experiences and conclusions. 

PMID- 24911642
TI  - Patient-specific instrumentation: total knee arthroplasty in sports medicine.

PMID- 24911643
TI  - Patient-specific instrumentation for the obese patient.

PMID- 24911644
TI  - The dual FAAH/MAGL inhibitor JZL195 has enhanced effects on endocannabinoid
      transmission and motor behavior in rats as compared to those of the MAGL
      inhibitor JZL184.
AB  - The biological actions of the endocannabinoids anandamide and 2-arachidonoyl
      glycerol (2-AG) are terminated by enzymatic hydrolysis of these lipids via fatty
      acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively.
      While several selective FAAH inhibitors have been developed and characterized in
      vitro and in vivo, none of the initial MAGL blockers have shown adequate potency
      and specificity for in vivo applications. More recently, a selective MAGL
      inhibitor, JZL184, has been shown to produce a long-lasting elevation of brain 2
      AG, as well as cannabinoid-like behavioral responses in mice. However, its
      effectiveness in rats remains controversial. Indeed, although JZL184 can elicit
      behavioral responses that are mediated, at least in part, via activation of
      cannabinoid CB1 receptors, several reports indicate that this compound does not
      alter 2-AG levels in this species. In this study we compared the behavioral and
      neurochemical effects of JZL 184 with those of the dual FAAH/MAGL inhibitor
      JZL195, and showed that systemic administration of the former can selectively
      elevate brain 2-AG in rats and produce motor suppression through a CB1
      independent mechanism. These findings indicate that, despite its lower potency
      against rat MAGL, JZL184 can be used to enhance 2-AG transmission and elicit
      behavioral responses in rodents. 

PMID- 24911645
TI  - Behavioral and neurochemical studies in mice pretreated with garcinielliptone FC
      in pilocarpine-induced seizures.
AB  - Garcinielliptone FC (GFC) isolated from hexanic fraction seed extract of species
      Platonia insignis Mart. It is widely used in folk medicine to treat skin diseases
      in both humans and animals as well as the seed decoction has been used to treat
      diarrheas and inflammatory diseases. However, there is no research on GFC effects
      in the central nervous system of rodents. The present study aimed to evaluate the
      GFC effects at doses of 25, 50 or 75 mg/kg on seizure parameters to determine
      their anticonvulsant activity and its effects on amino acid (gamma-aminobutyric
      acid (GABA), glutamine, aspartate and glutathione) levels as well as on
      acetylcholinesterase (AChE) activity in mice hippocampus after seizures. GFC
      produced an increased latency to first seizure, at doses 25mg/kg (20.12 +/- 2.20
      min), 50mg/kg (20.95 +/- 2.21 min) or 75 mg/kg (23.43 +/- 1.99 min) when compared
      with seized mice. In addition, GABA content of mice hippocampus treated with
      GFC75 plus P400 showed an increase of 46.90% when compared with seized mice. In
      aspartate, glutamine and glutamate levels detected a decrease of 5.21%, 13.55%
      and 21.80%, respectively in mice hippocampus treated with GFC75 plus P400 when
      compared with seized mice. Hippocampus mice treated with GFC75 plus P400 showed
      an increase in AChE activity (63.30%) when compared with seized mice. The results
      indicate that GFC can exert anticonvulsant activity and reduce the frequency of
      installation of pilocarpine-induced status epilepticus, as demonstrated by
      increase in latency to first seizure and decrease in mortality rate of animals.
      In conclusion, our data suggest that GFC may influence in epileptogenesis and
      promote anticonvulsant actions in pilocarpine model by modulating the GABA and
      glutamate contents and of AChE activity in seized mice hippocampus. This compound
      may be useful to produce neuronal protection and it can be considered as an
      anticonvulsant agent.

PMID- 24911646
TI  - Differential involvement of glutamate-gated chloride channel splice variants in
      the olfactory memory processes of the honeybee Apis mellifera.
AB  - Glutamate-gated chloride channels (GluCl) belong to the cys-loop ligand-gated ion
      channel superfamily and their expression had been described in several
      invertebrate nervous systems. In the honeybee, a unique gene amel_glucl encodes
      two alternatively spliced subunits, Amel_GluCl A and Amel_GluCl B. The expression
      and differential localization of those variants in the honeybee brain had been
      previously reported. Here we characterized the involvement of each variant in
      olfactory learning and memory processes, using specific small-interfering RNA
      (siRNA) targeting each variant. Firstly, the efficacy of the two siRNAs to
      decrease their targets' expression was tested, both at mRNA and protein levels.
      The two proteins showed a decrease of their respective expression 24h after
      injection. Secondly, each siRNA was injected into the brain to test whether or
      not it affected olfactory memory by using a classical paradigm of conditioning
      the proboscis extension reflex (PER). Amel_GluCl A was found to be involved only
      in retrieval of 1-nonanol, whereas Amel_GluCl B was involved in the PER response
      to 2-hexanol used as a conditioned stimulus or as new odorant. Here for the first
      time, a differential behavioral involvement of two highly similar GluCl subunits
      has been characterized in an invertebrate species. 

PMID- 24911647
TI  - Promotion of adipogenesis by an EP2 receptor agonist via stimulation of
      angiogenesis in pulmonary emphysema.
AB  - Body weight loss is a common manifestation in patients with chronic obstructive
      pulmonary disease (COPD), particularly those with severe emphysema. Adipose
      angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents
      may serve as a therapeutic option for lean COPD patients. Since angiogenesis is
      stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid
      (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a
      murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were
      intratracheally instilled with elastase or saline, followed after 4 weeks by
      intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous
      adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice
      treated with ONO-AE1-259, the SAT weight was largely restored, which was
      associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF
      protein production. In contrast, ONO-AE1-259 administration induced no alteration
      in the weight of the visceral adipose tissue. These results suggest that in EIE
      mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production,
      and thence, adipogenesis. Our data pave the way for the development of
      therapeutic interventions for weight loss in emphysema patients, e.g., use of pro
      angiogenic agents targeting the adipose tissue vascular component. 

PMID- 24911648
TI  - A case of iatrogenic stress? Results of the RCOG August rotation survey.
AB  - Although there are a number of studies of patient safety during the August
      rotation, they often focus on newly qualified doctors. It remains unclear whether
      negative impacts are due to doctors' inexperience, lack of technical skill or
      other aspects of rotation. This study used an electronic survey to seek the views
      of doctors working in obstetrics and gynaecology in the UK. A total of 1,879
      responses were received. The August rotation was felt to be a stressful time,
      with a negative effect on patient care (82%) and safety (73%), lasting up to 1
      month (62%). Although reducing services was thought to be helpful, there was
      strong support for staggering the rotation by grade (80%). This would ensure
      availability of doctors to cover services during the induction period, which
      should improve patient care and reduce staff stress. In addition, intensive
      skills training for junior staff and a supportive culture during the 1st month
      could optimise the integration and performance of doctors of all grades.

PMID- 24911649
TI  - Strigolactones inhibit caulonema elongation and cell division in the moss
      Physcomitrella patens.
AB  - In vascular plants, strigolactones (SLs) are known for their hormonal role and
      for their role as signal molecules in the rhizosphere. SLs are also produced by
      the moss Physcomitrella patens, in which they act as signaling factors for
      controlling filament extension and possibly interaction with neighboring
      individuals. To gain a better understanding of SL action at the cellular level,
      we investigated the effect of exogenously added molecules (SLs or analogs) in
      moss growth media. We used the previously characterized Ppccd8 mutant that is
      deficient in SL synthesis and showed that SLs affect moss protonema extension by
      reducing caulonema cell elongation and mainly cell division rate, both in light
      and dark conditions. Based on this effect, we set up bioassays to examine
      chemical structure requirements for SL activity in moss. The results suggest that
      compounds GR24, GR5, and 5-deoxystrigol are active in moss (as in pea), while
      other analogs that are highly active in the control of pea branching show little
      activity in moss. Interestingly, the karrikinolide KAR1, which shares molecular
      features with SLs, did not have any effect on filament growth, even though the
      moss genome contains several genes homologous to KAI2 (encoding the KAR1
      receptor) and no canonical homologue to D14 (encoding the SL receptor). Further
      studies should investigate whether SL signaling pathways have been conserved
      during land plant evolution. 

PMID- 24911650
TI  - Does improved survival lead to a more fragile population: time trends in second
      and third hospital admissions among men and women above the age of 60 in Sweden.
AB  - BACKGROUND: Life expectancy and time to first hospitalization have been
      prolonged, indicating that people live longer without needing hospital care. Life
      expectancy increased partially due to improved survival from severe diseases,
      which, however, could lead to a more fragile population. If so, time to a
      subsequent hospitalization could decrease. Alternatively, the overall trend of
      improved health could continue after the first hospitalization, prolonging also
      the time to subsequent hospitalizations. This study analyzes trends in subsequent
      hospitalizations among Swedish men and women above the age of 60, relating them
      to first hospitalization. It also looks at trends in the proportion of never
      hospitalized. METHODS: Individuals were followed in national registers for
      hospital admissions and deaths between 1972 and 2010. The proportion of never
      hospitalized individuals at given ages and time points, and the annual change in
      the risks of first and subsequent hospitalizations, were calculated. FINDINGS: An
      increase in the proportion of never hospitalized was seen over time. The risks of
      first as well as subsequent hospitalizations were reduced by almost 10% per
      decade for both men and women. Improvements were observed mainly for individuals
      below the ages of 90 and up to the year 2000. CONCLUSIONS: The reduction in
      annual risk of both first and subsequent hospitalizations up to 90 years of age
      speaks in favor of a postponement of the overall morbidity among the elderly and
      provides no support for the hypothesis that the population becomes more fragile
      due to increased survival from severe diseases.

PMID- 24911651
TI  - Regulation of mitotic cytoskeleton dynamics and cytokinesis by integrin-linked
      kinase in retinoblastoma cells.
AB  - During cell division integrin-linked kinase (ILK) has been shown to regulate
      microtubule dynamics and centrosome clustering, processes involved in cell cycle
      progression, and malignant transformation. In this study, we examine the effects
      of downregulating ILK on mitotic function in human retinoblastoma cell lines.
      These retinal cancer cells, caused by the loss of function of two gene alleles
      (Rb1) that encode the retinoblastoma tumour suppressor, have elevated expression
      of ILK. Here we show that inhibition of ILK activity results in a concentration
      dependent increase in nuclear area and multinucleated cells. Moreover, inhibition
      of ILK activity and expression increased the accumulation of multinucleated cells
      over time. In these cells, aberrant cytokinesis and karyokinesis correlate with
      altered mitotic spindle organization, decreased levels of cortical F-actin and
      centrosome de-clustering. Centrosome de-clustering, induced by ILK siRNA, was
      rescued in FLAG-ILK expressing Y79 cells as compared to those expressing FLAG-tag
      alone. Inhibition of ILK increased the proportion of cells exhibiting mitotic
      spindles and caused a significant G2/M arrest as early as 24 hours after exposure
      to QLT-0267. Live cell analysis indicate ILK downregulation causes an increase in
      multipolar anaphases and failed cytokinesis (bipolar and multipolar) of viable
      cells. These studies extend those indicating a critical function for ILK in
      mitotic cytoskeletal organization and describe a novel role for ILK in
      cytokinesis of Rb deficient cells. 

PMID- 24911652
TI  - Macrophage depletion disrupts immune balance and energy homeostasis.
AB  - Increased macrophage infiltration in tissues including white adipose tissue and
      skeletal muscle has been recognized as a pro-inflammatory factor that impairs
      insulin sensitivity in obesity. However, the relationship between tissue
      macrophages and energy metabolism under non-obese physiological conditions is not
      clear. To study a homeostatic role of macrophages in energy homeostasis, we
      depleted tissue macrophages in adult mice through conditional expression of
      diphtheria toxin (DT) receptor and DT-induced apoptosis. Macrophage depletion
      robustly reduced body fat mass due to reduced energy intake. These phenotypes
      were reversed after macrophage recovery. As a potential mechanism, severe
      hypothalamic and systemic inflammation was induced by neutrophil (NE)
      infiltration in the absence of macrophages. In addition, macrophage depletion
      dramatically increased circulating granulocyte colony-stimulating factor (G-CSF)
      which is indispensable for NE production and tissue infiltration. Our in vitro
      study further revealed that macrophages directly suppress G-CSF gene expression.
      Therefore, our study indicates that macrophages may play a critical role in
      integrating immune balance and energy homeostasis under physiological conditions.

PMID- 24911654
TI  - Political advocacy and practice barriers: a survey of Florida APRNs.
AB  - PURPOSE: This study examined factors aligned with advocacy among advanced
      practice registered nurses (APRNs) by examining the relationships among
      demographics, years of RN and APRN experience, education levels, affiliations
      with professional organizations, perceptions of barriers to practice, political
      activism, and willingness to speak to the media. DATA SOURCES: This was a
      secondary analysis of online survey data (N = 884) from APRNs in Florida. All
      APRNs with an e-mail address with the state nursing board or a Florida Coalition
      of Advanced Practice Nurses' membership organization received an e-mail
      requesting their participation to the survey. CONCLUSIONS: Having a high
      educational level and involvement in a professional organization are each
      individually statistically associated with perceiving practice barriers, engaging
      in political activism, and willingness to speak with media. Emerging nurse
      leaders need an understanding of policy issues, an appreciation of the potential
      of the profession, and enhanced advocacy skills. IMPLICATIONS FOR PRACTICE: To
      address the nation's health needs, APRNs need to recognize practice barriers,
      develop advocacy skills, and take action for policy changes to enhance the legal
      authority to practice to full extent of APRNs' education and training.

PMID- 24911653
TI  - An unexpected twist to the activation of IKKbeta: TAK1 primes IKKbeta for
      activation by autophosphorylation.
AB  - IKKbeta {IkappaB [inhibitor of NF-kappaB (nuclear factor kappaB)] kinase beta} is
      required to activate the transcription factor NF-kappaB, but how IKKbeta itself
      is activated in vivo is still unclear. It was found to require phosphorylation by
      one or more 'upstream' protein kinases in some reports, but by
      autophosphorylation in others. In the present study, we resolve this contro-versy
      by demonstrating that the activation of IKKbeta induced by IL-1 (interleukin-1)
      or TNF (tumour necrosis factor) in embryonic fibroblasts, or by ligands that
      activate Toll-like receptors in macrophages, requires two distinct
      phosphorylation events: first, the TAK1 [TGFbeta (transforming growth factor
      beta)-activated kinase-1]-catalysed phosphorylation of Ser177 and, secondly, the
      IKKbeta-catalysed autophosphorylation of Ser181. The phosphorylation of Ser177 by
      TAK1 is a priming event required for the subsequent autophosphorylation of
      Ser181, which enables IKKbeta to phosphorylate exogenous substrates. We also
      provide genetic evidence which indicates that the IL-1-stimulated, LUBAC (linear
      ubiquitin chain assembly complex)-catalysed formation of linear ubiquitin chains
      and their interaction with the NEMO (NF-kappaB essential modulator) component of
      the canonical IKK complex permits the TAK1-catalysed priming phosphorylation of
      IKKbeta at Ser177 and IKKalpha at Ser176. These findings may be of general
      significance for the activation of other protein kinases.

PMID- 24911655
TI  - Quantitative Spectral Analysis of Coherent Anti-Stokes Raman Scattering Signals:
      C-H Stretching Modes of the Methyl Group.
AB  - Coherent anti-Stokes Raman scattering (CARS) vibrational spectroscopy has been
      extensively developed into a powerful analytical technique to study various
      molecules. Quantitative interpretation of CARS spectra can help to improve CARS
      for chemical analysis and extend its analytical applications. In this work, we
      quantitatively analyzed CARS signals originating from the methyl groups in
      poly(dimethylsiloxane) (PDMS), with the help of the bond additivity method.
      Experimentally, a home-built CARS spectrometer modified from a commercial sum
      frequency generation spectrometer was used to collect CARS spectra from a PDMS
      film. Theoretically, we successfully reproduced the peak intensity ratio of C-H
      symmetric and asymmetric stretching modes of the PDMS methyl group in different
      polarization combinations based on bond additivity method and Raman
      depolarization ratio. This research shows that bond additivity theory can help to
      obtain the third-order nonlinear susceptibility tensor properties probed by
      different polarization combinations used in CARS spectroscopy. The method
      developed in this work could also be applied to CARS vibrational stretching
      analysis of other functional groups, providing quantitative understanding of CARS
      spectrum for applications in spectroscopy.

PMID- 24911656
TI  - Oxirapentyns F-K from the marine-sediment-derived fungus Isaria felina KMM 4639.
AB  - Six new highly oxygenated chromene derivatives, oxirapentyns F-K (2-7), one new
      polyketide (8), one new benzofurane (9), and two known cyclodepsipeptides,
      isoisariin B and isaridin E, were isolated from the lipophilic extract of the
      marine-derived fungus Isaria felina KMM 4639. The structures of compounds 2-9
      were determined using spectroscopic methods. The relative configurations of
      compounds 2-7 were established through a combination of NOE data and spin
      coupling constants, and these results were confirmed by X-ray crystallographic
      analysis of 4. The absolute structures of all oxirapentyns were assumed based on
      their biogenetic relationship and confirmed using the modified Mosher's method on
      2 and 7. Isariketide (8) showed moderate cytotoxicity toward HL-60 cells. 

PMID- 24911658
TI  - Efficacy and safety of polymyxins for the treatment of Acinectobacter baumannii
      infection: a systematic review and meta-analysis.
AB  - BACKGROUND: Multi-drug resistance among Acinetobacter baumannii increases the
      need for polymyxins. We conducted a meta-analysis aimed to assess the efficacy
      and safety of polymyxins for the treatment of Acinetobacter baumannii infection.
      METHODS: We searched PUBMED, EMBASE, the Cochrane Central Register of Controlled
      Trials (CENTRAL), CNKI, Chinese Biomedical Literature Database up to November 1,
      2013, to identify published studies, and we searched clinical trial registries to
      identify completed unpublished studies. Randomized controlled trials and cohort
      studies were considered for inclusion. Data were extracted on clinical response,
      microbiological response, mortality, length of stay and adverse events. RESULTS:
      12 controlled studies, comparing 677 patients, were included. Although clinical
      (odds ratio 1.421, 95% confidence interval 0.722-2.797) and microbiological (OR
      1.416, 95% CI 0.369-5.425) response rates favored the polymyxins group, these
      differences were not significant. Treatment with polymyxins vs. controls did not
      affect hospital mortality (OR 0.506, 95% CI 0.101-2.536), lengths of hospital
      stay (standard mean difference -0.221, 95% CI 0.899-0.458) or nephrotoxicity (OR
      1.192, 95% CI 0.436-3.261). The combination of polymyxins with other antibiotics
      achieved similar clinical response rates to its monotherapy regimen (OR 0.601,
      95% CI 0.320-1.130). CONCLUSIONS: Our results suggest that polymyxins may be as
      safe and as efficacious as standard antibiotics for the treatment of A. baumannii
      infection. There is no strong evidence that combination regimen of polymyxins is
      superior to monotherapy regimen.

PMID- 24911657
TI  - Human prominin-1 (CD133) is detected in both neoplastic and non-neoplastic
      salivary gland diseases and released into saliva in a ubiquitinated form.
AB  - Prominin-1 (CD133) is physiologically expressed at the apical membranes of
      secretory (serous and mucous) and duct cells of major salivary glands. We
      investigated its expression in various human salivary gland lesions using two
      distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133) applied on
      paraffin-embedded sections and characterized its occurrence in saliva. The 80B258
      epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent
      in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid
      carcinoma. The 80B258 immunoreactivity was predominately detected at the apical
      membrane of tumor cells showing acinar or intercalated duct cell differentiation,
      which lined duct- or cyst-like structures, and in luminal secretions. It was
      observed on the whole cell membrane in non-luminal structures present in the
      vicinity of thin-walled blood vessels and hemorrhagic areas in adenoid cystic
      carcinoma. Of note, AC133 labeled only a subset of 80B258-positive structures. In
      peritumoral salivary gland tissues as well as in obstructive sialadenitis, an up
      regulation of prominin-1 (both 80B258 and AC133 immunoreactivities) was observed
      in intercalated duct cells. In most tissues, prominin-1 was partially co
      expressed with two cancer markers: carcinoembryonic antigen (CEA) and mucin-1
      (MUC1). Differential centrifugation of saliva followed by immunoblotting
      indicated that all three markers were released in association with small membrane
      vesicles. Immuno-isolated prominin-1-positive vesicles contained CEA and MUC1,
      but also exosome-related proteins CD63, flotillin-1, flotillin-2 and the adaptor
      protein syntenin-1. The latter protein was shown to interact with prominin-1 as
      demonstrated by its co-immunoisolation. A fraction of saliva-associated prominin
      1 appeared to be ubiquitinated. Collectively, our findings bring new insights
      into the biochemistry and trafficking of prominin-1 as well as its
      immunohistochemical profile in certain types of salivary gland tumors and
      inflammatory diseases. 

PMID- 24911659
TI  - Haploinsufficiency of XPO1 and USP34 by a de novo 230 kb deletion in 2p15, in a
      patient with mild intellectual disability and cranio-facial dysmorphisms.
AB  - 2p15p16.1-deletion syndrome was first described in 2007 based on the clinical
      presentation of two patients. The syndrome is characterized by intellectual
      disability, autism spectrum disorders, microcephaly, dysmorphic facial features
      and a variety of congenital organ defects. The precise genotype-phenotype
      correlation in 2p15-deletion syndrome is not understood. However, greater insight
      can be obtained by thorough clinical investigation of patients carrying
      deletions, especially those of small size. We report a 21-year-old male patient
      with features overlapping the clinical spectrum of the 2p15p16.1-deletion
      syndrome, such as intellectual disability, dysmorphic facial features, and
      congenital defects. He carried a 230 kb de novo deletion (chr2:61500346-61733075
      bp, hg19), which affects the genes USP34, SNORA70B and XPO1. While there is a
      lack of functional data on SNORA70B, the involvement of USP34 and XPO1 in the
      regulation of fundamental developmental processes is well known. We suggest that
      haploinsufficiency of one or both of these genes is likely to be responsible for
      the disease in our patient. 

PMID- 24911661
TI  - Electron microscopic observation of the sagittal structure of Drosophila mature
      sperm.
AB  - Observation of sperm development and determination of their morphological
      characteristics are very important to the understanding of phylogenetic
      relationships and the study of sperm function during fertilization. Although
      ultrastructural studies of sperm development in the testes of the fruit fly
      Drosophila have been performed, there are few reports describing electron
      microscopic morphology of mature sperm, that is, those released from the testes
      to the seminal vesicles. Here, we present the first report of the sagittal
      organization of Drosophila sperm head and neck regions by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). The head and tail
      structures of a mature sperm, for example, the acrosome, nucleus, and flagellum,
      were easy to distinguish by the morphological characteristics of the sperm
      surface by SEM. The morphological relationships between the surface and internal
      structures of mature sperm were confirmed by observing longitudinal sections with
      TEM. Our approach overcame the technical difficulties involved in sample
      preparation for electron microscopic observation of the Drosophila mature sperm
      head, and therefore, this study serves as an important foundation for future
      genetic dissection of sperm ultrastructure and function in male sterile mutants.

PMID- 24911660
TI  - Neural pathfinding on uni- and multidirectional photopolymerized micropatterns.
AB  - Overcoming signal resolution barriers of neural prostheses, such as the
      commercially available cochlear impant (CI) or the developing retinal implant,
      will likely require spatial control of regenerative neural elements. To
      rationally design materials that direct nerve growth, it is first necessary to
      determine pathfinding behavior of de novo neurite growth from prosthesis-relevant
      cells such as spiral ganglion neurons (SGNs) in the inner ear. Accordingly, in
      this work, repeating 90 degrees  turns were fabricated as multidirectional
      micropatterns to determine SGN neurite turning capability and pathfinding.
      Unidirectional micropatterns and unpatterned substrates are used as comparisons.
      Spiral ganglion Schwann cell alignment (SGSC) is also examined on each surface
      type. Micropatterns are fabricated using the spatial reaction control inherent to
      photopolymerization with photomasks that have either parallel line spacing
      gratings for unidirectional patterns or repeating 90 degrees  angle steps for
      multidirectional patterns. Feature depth is controlled by modulating UV exposure
      time by shuttering the light source at given time increments. Substrate
      topography is characterized by white light interferometry and scanning electron
      microscopy (SEM). Both pattern types exhibit features that are 25 MUm in width
      and 7.4 +/- 0.7 MUm in depth. SGN neurites orient randomly on unpatterned
      photopolymer controls, align and consistently track unidirectional patterns, and
      are substantially influenced by, but do not consistently track, multidirectional
      turning cues. Neurite lengths are 20% shorter on multidirectional substrates
      compared to unidirectional patterns while neurite branching and microfeature
      crossing events are significantly higher. For both pattern types, the majority of
      the neurite length is located in depressed surface features. Developing methods
      to understand neural pathfinding and to guide de novo neurite growth to specific
      stimulatory elements will enable design of innovative biomaterials that improve
      functional outcomes of devices that interface with the nervous system. 

PMID- 24911662
TI  - Cancer patients acceptance, understanding, and willingness-to-pay for
      pharmacogenomic testing.
AB  - BACKGROUND: Pharmacogenomics is gaining increasing importance in the therapeutics
      of cancer; yet, there is little knowledge of cancer patients' attitudes toward
      the use of pharmacogenomic testing in clinical practice. We carried out this
      study to explore cancer patients' acceptance, understanding, and willingness-to
      pay for pharmacogenomic testing. MATERIALS AND METHODS: A broad cross-section of
      gastrointestinal, lung, breast, and other cancer patients were interviewed in
      terms of their acceptance of pharmacogenomic testing using hypothetical time,
      efficacy, and toxicity trade-off and willingness-to-pay scenarios. RESULTS: Among
      the 96% of 123 adjuvant patients accepting chemotherapy under optimal conditions,
      99% wanted pharmacogenomic testing that could identify a subset of patients
      benefiting from chemotherapy, accepting median incurred costs of $2000 (range $0
      25,000) and turnaround time for test results of 16 days (range 0-90 days). Among
      the 97% of 121 metastatic patients accepting chemotherapy, 97.4% wanted
      pharmacogenomic testing that could detect the risk of severe toxicity, accepting
      median incurred costs of $1000 (range $0-10,000) and turnaround time for results
      of 14 days (range 1-90 days). The majority of patients wanted to be involved in
      decision-making on pharmacogenomic testing; however, one in five patients lacked
      a basic understanding of pharmacogenomic testing. CONCLUSION: Among cancer
      patients willing to undergo chemotherapy, almost all wanted pharmacogenomic
      testing and were willing-to-pay for it, waiting several weeks for results.
      Although patients had a strong desire to be involved in decision-making on
      pharmacogenomic testing, a considerable proportion lacked the necessary knowledge
      to make informed choices.

PMID- 24911663
TI  - Impact of cytochrome P450 3A5 polymorphism in graft livers on the frequency of
      acute cellular rejection in living-donor liver transplantation.
AB  - OBJECTIVE: We investigated whether the cytochrome P450 3A5*3 (CYP3A5*3) genotype
      affects tacrolimus pharmacokinetics and the risk of acute cellular rejection in
      living-donor liver transplant patients in Japan. MATERIALS AND METHODS: Between
      July 2004 and June 2011, we enrolled 410 living-donor liver transplant patients
      receiving tacrolimus. Biopsy specimens of intestinal mucosa and graft liver at
      surgery were obtained to examine the mRNA expression of CYP3A subfamilies as well
      as the genotyping of CYP3A5*3 polymorphism. RESULTS: The CYP3A5 genotype in the
      native intestine had no significant effect on the occurrence of acute cellular
      rejection between postoperative days 14 and 23 in cases with identical or
      compatible ABO blood types (11.5% for the CYP3A5*1 allele vs. 7.4% for
      CYP3A5*3/*3; P=0.2643), although the concentration/dose ratio of tacrolimus was
      significantly higher in patients with the intestinal CYP3A5*3/*3 genotype than in
      those with the CYP3A5*1 allele for 5 post-transplant weeks. However, patients who
      received a graft liver with the CYP3A5*1 allele showed a higher rate of acute
      cellular rejection than those who received a graft liver with the CYP3A5*3/*3
      genotype (14.5 vs. 5.7%; P=0.0134). The relative risk for acute cellular
      rejection associated with the CYP3A5*1 liver allele was 2.629 (P=0.018, Cox
      regression model). Consequently, graft liver CYP3A5*1 genotype might increase the
      risk for acute cellular rejection after living-donor liver transplantation,
      possibly by associating with the local hepatic tacrolimus concentration.
      CONCLUSIONS: The target level of tacrolimus may be affected by the CYP3A5*3
      genotype of the liver, rather than by that of the small intestine, after
      postoperative day 14.

PMID- 24911664
TI  - Etiology and Clinical Features of Ocular Inflammatory Diseases in a Tertiary
      Center in Lebanon.
AB  - PURPOSE: To identify the pattern of uveitis in patients presenting to the
      American University of Beirut Medical Center (AUBMC) uveitis service in Lebanon.
      METHODS: The charts of patients seen between January 2009 and September 2011 were
      retrospectively reviewed. Data pertaining to patient demographics, eye
      examination on presentation, workup, and final diagnoses were collected. RESULTS:
      The total number of charts reviewed was 209. The most common noninfectious
      etiologies were Behcet disease, sarcoidosis, and HLA-B27-associated uveitis,
      while toxoplasmosis, herpes, and tuberculosis were the most common infectious
      etiologies. The mean duration of the disease before presentation to our center
      was 38 +/- 56 months (range 0-284 months), with cataract formation in 90/234
      (38%) and visual impairment in 134/291 (46%) eyes on presentation. CONCLUSIONS:
      This case series reveals a significant delay in referring uveitis cases to a
      specialized center, which may contribute to the high percentage of patients
      presenting with ocular complications.

PMID- 24911665
TI  - S-100beta does not predict outcome after mild traumatic brain injury.
AB  - OBJECTIVE: To determine the usefulness of S-100beta, a marker for central nervous
      system damage, in the prediction of long-term outcomes after mild traumatic brain
      injury (MTBI) Hypothesis: Mid- and long-term outcomes of MTBI (i.e. 3, 6 and 12
      months post-injury and return-to-work or school (RTWS)) may be predicted based on
      pre-injury and injury factors as well as S-100beta. METHODS: MTBI subjects
      without abnormal brain computed tomography requiring intervention, focal
      neurological deficits, seizures, amnesia > 24 hours and severe or multiple
      injuries were recruited at a level I trauma centre. Admission S-100beta
      measurements and baseline Concussion Symptom Checklist were obtained. Symptoms
      and RTWS were re-assessed at follow-up visits (3-10 days and 3, 6 and 12 months).
      Outcomes included number of symptoms and RTWS at follow-up. Chi-square tests,
      linear and logistic regression models were used and p < 0.05 was considered
      statistically significant. RESULTS: One hundred and fifty of 180 study subjects
      had S-100beta results. Eleven per cent were unable to RTWS at 12 months. S
      100beta levels were not associated with post-concussive symptomatology at follow
      up. In addition, no association was found between S-100beta levels and RTWS.
      CONCLUSION: Amongst MTBI patients, S-100beta levels are not associated with
      prolonged post-concussive syndrome or the inability to RTWS.

PMID- 24911666
TI  - Hydroxylated, methoxylated, and parent polybrominated diphenyl ethers (PBDEs) in
      the inland environment, Korea, and potential OH- and MeO-BDE source.
AB  - The concentrations, congener profiles, and phase-specific distribution profiles
      of 27 polybrominated diphenyl ethers and 10 hydroxylated and 18 methoxylated
      brominated diphenyl ethers (OH- and MeO-BDEs; later called structural analogues
      of PBDEs) were determined in surface soil, water, air, and vegetation from the
      southeastern city of Busan, Korea for 2010-2011. The total PBDE concentrations
      were 0.18-7.7 ng/g in soil, 6.3-87 pg/L [corrected] in water, 5.3-16 pg/m(3) in
      air, and 0.06-0.22 ng/g in vegetation. The OH- and MeO-BDE concentrations were
      lower than the parent PBDE concentrations in soil samples but OH-BDEs were much
      greater in the water samples and MeO-BDEs were much greater in the air samples.
      The relative concentrations of the PBDEs and their structural analogues varied
      depending on the type and homologue of the degradation product, the substituent
      position, and the characteristics of the environmental medium. In particular, the
      OH-BDEs were not found in air samples and the OH-penta BDEs were not detected in
      any of the matrices. The dominance of the ortho-substituted structural analogues
      found in water and vegetation suggested that they may have natural sources, but
      different substituent patterns were found in the air and soil samples, suggesting
      that the structural analogues had different formation mechanisms in these media.

PMID- 24911667
TI  - Biotransformation of resibufogenin by Actinomucor elegans.
AB  - Resibufogenin (RB), a major bioactive bufadienolide, has the potential anticancer
      activity. In the present work, biotransformation of RB by Actinomucor elegans AS
      3.2778 yielded five products, namely 3-oxo-resibufogenin (1), 3-epi-resibufogenin
      (2), 3-epi-12-oxo-hydroxylresibufogenin (3), 3alpha-acetoxy-15alpha
      hydroxylbufalin (4), and 3-epi-12alpha-hydroxylresibufogenin (5), respectively.
      Among them, metabolites 3 and 4 are previously unreported. The chemical
      structures of metabolites 1-5 were fully elucidated on the basis of 2D NMR and HR
      MS. The highly stereo- and regio-specific isomerization, hydroxylation, and
      esterification reactions were observed in the biotransformation process of RB by
      A. elegans. Their cytotoxicities against A549 and H1299 cells were evaluated. 

PMID- 24911668
TI  - Multiscale characterization of acrylic bone cement modified with functionalized
      mesoporous silica nanoparticles.
AB  - Acrylic bone cement is widely used to anchor orthopedic implants to bone and
      mechanical failure of the cement mantle surrounding an implant can contribute to
      aseptic loosening. In an effort to enhance the mechanical properties of bone
      cement, a variety of nanoparticles and fibers can be incorporated into the cement
      matrix. Mesoporous silica nanoparticles (MSNs) are a class of particles that
      display high potential for use as reinforcement within bone cement. Therefore,
      the purpose of this study was to quantify the impact of modifying an acrylic
      cement with various low-loadings of mesoporous silica. Three types of MSNs (one
      plain variety and two modified with functional groups) at two loading ratios (0.1
      and 0.2wt/wt) were incorporated into a commercially available bone cement. The
      mechanical properties were characterized using four-point bending,
      microindentation and nanoindentation (static, stress relaxation, and creep) while
      material properties were assessed through dynamic mechanical analysis,
      differential scanning calorimetry, thermogravimetric analysis, FTIR spectroscopy,
      and scanning electron microscopy. Four-point flexural testing and nanoindentation
      revealed minimal impact on the properties of the cements, except for several
      changes in the nano-level static mechanical properties. Conversely,
      microindentation testing demonstrated that the addition of MSNs significantly
      increased the microhardness. The stress relaxation and creep properties of the
      cements measured with nanoindentation displayed no effect resulting from the
      addition of MSNs. The measured material properties were consistent among all
      cements. Analysis of scanning electron micrographs images revealed that surface
      functionalization enhanced particle dispersion within the cement matrix and
      resulted in fewer particle agglomerates. These results suggest that the loading
      ratios of mesoporous silica used in this study were not an effective
      reinforcement material. Future work should be conducted to determine the impact
      of higher MSN loading ratios and alternative functional groups. 

PMID- 24911669
TI  - Effectiveness of antiepileptic drug combination therapy for partial-onset
      seizures based on mechanisms of action.
AB  - IMPORTANCE: To our knowledge, the current study is the first to describe
      antiepileptic drug (AED) combination therapy patterns according to their
      mechanism of action (MOA) in a real-world setting and to evaluate the differences
      in outcomes comparing different-MOA combination therapy with same-MOA combination
      therapy for patients with partial-onset seizure. OBJECTIVE: To compare treatment
      persistence and health care use with AED combinations categorized by MOA in
      patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS: Using
      the Truven Health MarketScan Commercial Claims Database containing 96 million
      covered lives from July 1, 2004, through March 31, 2011, adults with concomitant
      use of 2 different AEDs and a recent partial-onset seizure diagnosis were
      selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers
      (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding
      (SV2), and multiple mechanisms (M). Patients were assigned a combination category
      based on their concomitant AED use. MAIN OUTCOMES AND MEASURES: Treatment
      persistence was measured from the start of AED combination therapy until the end
      of the combination. Health care resource use was measured during the combination
      treatment duration. Multivariate analyses evaluated AED discontinuation risk and
      health care use according to MOA combinations. RESULTS: Distribution of 8615
      selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M,
      13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same
      MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344
      [345] days and 513 [530] days, respectively) and greater hazard of
      discontinuation compared with different-MOA combinations. Patients with different
      MOA G combinations had a significantly lower risk for inpatient admission (odds
      ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations.
      Patients with different-MOA SC combinations had significantly lower risks for
      emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03)
      compared with SC+SC combinations. CONCLUSIONS AND RELEVANCE: The findings suggest
      that AED combinations with different MOAs have greater effectiveness as measured
      by treatment persistence and lower risks for hospitalization and emergency
      department visits. Further research is needed to more fully understand the role
      of the MOA in achieving optimal outcomes.

PMID- 24911670
TI  - Frequency of monoclonal gammopathy in psoriatic patients receiving anti-TNF
      therapy compared with patients taking conventional drugs: a cross-sectional
      study.

PMID- 24911671
TI  - Evolution of early development in dipterans: reverse-engineering the gap gene
      network in the moth midge Clogmia albipunctata (Psychodidae).
AB  - Understanding the developmental and evolutionary dynamics of regulatory networks
      is essential if we are to explain the non-random distribution of phenotypes among
      the diversity of organismic forms. Here, we present a comparative analysis of one
      of the best understood developmental gene regulatory networks today: the gap gene
      network involved in early patterning of insect embryos. We use gene circuit
      models, which are fitted to quantitative spatio-temporal gene expression data for
      the four trunk gap genes hunchback (hb), Kruppel (Kr), giant (gt), and knirps
      (kni)/knirps-like (knl) in the moth midge Clogmia albipunctata, and compare them
      to equivalent reverse-engineered circuits from our reference species, the vinegar
      fly Drosophila melanogaster. In contrast to the single network structure we find
      for D. melanogaster, our models predict four alternative networks for C.
      albipunctata. These networks share a core structure, which includes the central
      regulatory feedback between hb and knl. Other interactions are only partially
      determined, as they differ between our four network structures. Nevertheless, our
      models make testable predictions and enable us to gain specific insights into gap
      gene regulation in C. albipunctata. They suggest a less central role for Kr in C.
      albipunctata than in D. melanogaster, and show that the mechanisms causing an
      anterior shift of gap domains over time are largely conserved between the two
      species, although shift dynamics differ. The set of C. albipunctata gene circuit
      models presented here will be used as the starting point for data-constrained in
      silico evolutionary simulations to study patterning transitions in the early
      development of dipteran species.

PMID- 24911672
TI  - Systemic abnormalities in children with congenital optic disc excavations.
AB  - PURPOSE: Together with optic disc hypoplasia, excavated optic disc anomalies
      represent the most frequent congenital abnormality involving the optic nerve
      head. The purpose of the present study was to retrospectively review the results
      of a screening for extraocular abnormalities in children presenting with
      congenital optic disc excavations. MATERIALS AND METHODS: The medical records of
      37 patients diagnosed with a unilateral or bilateral non glaucomatous optic disc
      excavation were retrospectively reviewed to analyze the result of the extra
      ocular evaluation and to report the associated ocular abnormalities. RESULTS: An
      ocular abnormality was observed in conjunction with the excavated optic disc in
      31% of the eyes. The systematic investigations revealed the presence of at least
      one extra-ocular disorder in 48% of the cases, and the optic disc excavation
      could be considered as syndromic in 30% of patients. The prevalence of
      extraocular malformations was significantly higher in infants presenting with
      associated ocular malformations or abnormal vision/development. CONCLUSIONS: The
      present study suggests that a systematic approach to search for any associated
      systemic abnormalities could be envisioned in patients presenting with congenital
      excavated optic discs, and particularly those presenting with abnormal vision,
      associated ocular defects or abnormal development.

PMID- 24911673
TI  - Tadalafil inhibits the cAMP stimulated glucose output in the rat liver.
AB  - The purpose of the present work was to verify if tadalafil affects hepatic
      glucose output, one of the primary targets of cAMP, in the isolated perfused rat
      liver. No effects on glycogen catabolism and oxygen uptake were found under basal
      conditions for tadalafil concentrations in the range between 0.25 and 10 MUM.
      However, tadalafil had a clear and time-dependent inhibitory effect on the cAMP-
      and glucagon-stimulated glucose release. Constant infusion of tadalafil in the
      range between 0.25 and 10 MUM eventually abolished 100% of the stimulatory action
      of those effectors. The tadalafil concentrations producing half-maximal rates of
      inhibition of the cAMP and glucagon stimulated glycogenolysis were 0.46+/-0.04
      and 1.07+/-0.16 MUM, respectively. These concentrations are close to the plasma
      peak concentrations in patients after ingestion of 20 mg tadalafil. The drug also
      diminished the activity of glycogen phosphorylase a and increased the activities
      of glucose 6-phosphatase, glucokinase, pyruvate kinase and glucose 6-phosphate
      dehydrogenase. These actions occurred only in the cellular environment. Tadalafil
      did not affect binding of cAMP to protein kinase A. Diminution of cAMP-stimulated
      glucose output is the opposite of what can be expected from a phosphodiesterase
      inhibition, the most common effect attributed to tadalafil. Diminution of glucose
      output by tadalafil can be attributed (a) to an interference with glycogen
      phosphorylase stimulation and (b) to an increased futile cycling of glucose 6
      phosphate and glucose with a concomitant increased flow of hexose units into
      cellular metabolic pathways. The effects described in the present work may prove
      to represent important side effects of tadalafil.

PMID- 24911674
TI  - The history of hemophilia.
AB  - Hemophilia A and B are rare inherited bleeding disorders characterized by the
      deficiency of coagulation factor VIII (FVIII) or factor IX (FIX). While the
      history of hemophilia dates back to the 2nd century AD, a modern description of
      hemophilia appeared only at the beginning of the 19th century. The discovery of
      "antihemophilic globulin" in the middle of the 20th century paved the way to the
      production of cryoprecipitate and then of FVIII and FIX concentrates. Barring the
      tragic consequences on the hemophilia community of the transmission of blood
      borne viruses by nonvirus inactivated factor concentrates during the 1970s and
      1980s, plasma-derived first and recombinant products later revolutionized the
      treatment of hemophilia through the widespread adoption of home treatment and
      prophylaxis regimens, which dramatically improved the quality of life and life
      expectancy of persons with hemophilia during the past decade. This article
      briefly reviews the most important stages of the management of hemophilia from
      the past century up to the present days.

PMID- 24911675
TI  - Sticky platelet syndrome: history and future perspectives.
AB  - The sticky platelet syndrome (SPS) is a thrombophilic qualitative platelet
      disorder with familial occurrence and autosomal dominant trait, characterized by
      increased in vitro platelet aggregation after low concentrations of adenosine
      diphosphate and/or epinephrine. Its clinical manifestation includes arterial
      thrombosis, pregnancy complications (fetal growth retardation and fetal loss),
      and less often venous thromboembolism. SPS was considered to be a rare
      thrombophilic disorder, but it can be found relatively often as a cause of
      unexplained thrombosis, particularly among patients with arterial thrombosis such
      as stroke. The syndrome was recognized as a distinct disorder in 1983 by Holiday
      and further characterized in the 1980s and 1990s, with Mammen and Bick providing
      the key findings. Although recognized for more than 30 years, significant issues,
      namely the syndrome's etiology, inheritance, and epidemiology, remain unclear.
      The aim of the first part of this review is to summarize the previous 35 years of
      the research into, and to provide a brief historical account of, SPS. The history
      section is focused particularly on the work of two most prominent investigators:
      Eberhard F. Mammen and Rodger L. Bick. The second part summarizes the present
      understanding of the syndrome and outlines unresolved issues and the trends in
      which the future research is likely to continue.

PMID- 24911676
TI  - Risk factors and surgical interventions associated with primary postpartum
      haemorrhage unresponsive to first-line therapies.
AB  - The aim of this study was to investigate risk factors and surgical interventions
      associated with primary postpartum haemorrhage (PPH) unresponsive to first-line
      therapies. A retrospective analysis was performed of 212 women who experienced
      primary PPH (blood loss >= 500 ml). Logistic regression analysis identified that
      caesarean section (odds ratio [OR] 2.745; 95% confidence interval [CI], 1.063
      7.085; p = 0.037) and abnormal placental adhesion (OR 3.823; 95% CI, 1.333
      10.963; p = 0.013) were risk factors for PPH unresponsive to first-line
      therapies. There was no significant difference in blood loss, blood transfusion
      and success rate among intrauterine tamponade, B-Lynch suture and uterine artery
      ligation. Intrauterine tamponade is the least invasive and most rapid approach,
      so it should be taken as the first choice for surgical management after
      unresponsiveness to first-line therapies.

PMID- 24911679
TI  - The critical need for improved enumeration and surveillance of the logging
      workforce.

PMID- 24911678
TI  - Raising the profile of worker safety: highlights of the 2013 North American
      Agricultural Safety Summit.
AB  - The 2013 North American Agricultural Safety Summit, an unprecedented gathering of
      industry leaders and safety experts, was held September 25-27 in Minneapolis, MN.
      Hosted by the industry-led Agricultural Safety and Health Council of America
      (ASHCA), there were 250 attendees, 82 speakers, 76 abstracts with poster
      presentations, along with "best practices" videos, genius bars sessions, learning
      stations, exhibits, breakfast roundtable topics, and receptions. The event was a
      mix of knowledge, inspiration and networking to enable participants to influence
      the adoption of safety practices in their home/work settings. Given the
      agriculture industry's commitment to feed nine billion people, the projected
      world population by 2050, it is imperative that producers and agribusiness strive
      to do it safely, humanely and sustainably. Evaluation feedback was very positive,
      indicating ASHCA's original objectives for the Summit were achieved.

PMID- 24911680
TI  - A model health and safety intervention for Hispanic immigrants working in the
      dairy industry.

PMID- 24911681
TI  - Safety and health in biomass production, transportation, and storage: a
      commentary based on the biomass and biofuels session at the 2013 North American
      Agricultural Safety Summit.
AB  - There is significant interest in biomass production ranging from government
      agencies to the private sector, both inside and outside of the traditional
      production agricultural setting. This interest has led to an increase in the
      development and production of biomass crops. Much of this effort has focused on
      specific segments of the process, and more specifically on the mechanics of these
      individual segments. From a review of scientific literature, it is seen that
      little effort has been put into identifying, classifying and preventing safety
      hazards in on-farm biomass production systems. This commentary describes the
      current status of the knowledge pertaining to health and safety factors of
      biomass production and storage in the US and identifies areas of standards
      development that the biomass industry needs from the agricultural safety and
      health community.

PMID- 24911682
TI  - Ergonomics training in the commercial fishing industry: emerging issues and gaps
      in knowledge.

PMID- 24911683
TI  - Farm Mapping to Assist, Protect, and Prepare Emergency Responders: Farm MAPPER.
AB  - Responders such as firefighters and emergency medical technicians who respond to
      farm emergencies often face complex and unknown environments. They may encounter
      hazards such as fuels, solvents, pesticides, caustics, and exploding gas storage
      cylinders. Responders may be unaware of dirt roads within the farm that can
      expedite their arrival at critical sites or snow-covered manure pits that act as
      hidden hazards. A response to a farm, unless guided by someone familiar with the
      operation, may present a risk to responders and post a challenge in locating the
      victim. This project explored the use of a Web-based farm-mapping application
      optimized for tablets and accessible via easily accessible on-site matrix
      barcodes, or quick response codes (QR codes), to provide emergency responders
      with hazard and resource information to agricultural operations. Secured portals
      were developed for both farmers and responders, allowing both parties to populate
      and customize farm maps with icons. Data were stored online and linked to QR
      codes attached to mailbox posts where emergency responders may read them with a
      mobile device. Mock responses were conducted on dairy farms to test QR code
      linking efficacy, Web site security, and field usability. Findings from farmer
      usability tests showed willingness to enter data as well as ease of Web site
      navigation and data entry even with farmers who had limited computer knowledge.
      Usability tests with emergency responders showed ease of QR code connectivity to
      the farm maps and ease of Web site navigation. Further research is needed to
      improve data security as well as assess the program's applicability to nonfarm
      environments and integration with existing emergency response systems. The next
      phases of this project will expand the program for regional and national use,
      develop QR code-linked, Web-based extrication guidance for farm machinery for
      victim entrapment rescue, and create QR code-linked online training videos and
      materials for limited English proficient immigrant farm workers.

PMID- 24911684
TI  - Assessing the effectiveness of the Pesticides and Farmworker Health Toolkit: a
      curriculum for enhancing farmworkers' understanding of pesticide safety concepts.
AB  - Among agricultural workers, migrant and seasonal farmworkers have been recognized
      as a special risk population because these laborers encounter cultural challenges
      and linguistic barriers while attempting to maintain their safety and health
      within their working environments. The crop-specific Pesticides and Farmworker
      Health Toolkit (Toolkit) is a pesticide safety and health curriculum designed to
      communicate to farmworkers pesticide hazards commonly found in their working
      environments and to address Worker Protection Standard (WPS) pesticide training
      criteria for agricultural workers. The goal of this preliminary study was to test
      evaluation items for measuring knowledge increases among farmworkers and to
      assess the effectiveness of the Toolkit in improving farmworkers' knowledge of
      key WPS and risk communication concepts when the Toolkit lesson was delivered by
      trained trainers in the field. After receiving training on the curriculum, four
      participating trainers provided lessons using the Toolkit as part of their
      regular training responsibilities and orally administered a pre- and post-lesson
      evaluation instrument to 20 farmworker volunteers who were generally
      representative of the national farmworker population. Farmworker knowledge of
      pesticide safety messages significantly (P<.05) increased after participation in
      the lesson. Further, items with visual alternatives were found to be most useful
      in discriminating between more and less knowledgeable farmworkers. The pilot
      study suggests that the Pesticides and Farmworker Health Toolkit is an effective,
      research-based pesticide safety and health intervention for the at-risk
      farmworker population and identifies a testing format appropriate for evaluating
      the Toolkit and other similar interventions for farmworkers in the field.

PMID- 24911685
TI  - Reducing stress to minimize injury: the nation's first employee assistance
      program for dairy farmers.
AB  - This commentary describes the nation's first Employee Assistance Program (EAP)
      for dairy farmers. It discusses (1) the significant financial strain and
      emotional stress experienced by Vermont's dairy farmers reaching dangerous
      levels; (2) the effect of stress and anxiety on workplace safety; and (3) the
      highly effective role of an EAP in reducing stress. The commentary depicts the
      Farm First program model of prevention and early intervention services for dairy
      farmers that include short-term solution-focused counseling, resources, and
      referrals to help farmers address the stressors they confront daily. The Farm
      First program mitigates depression, anxiety, financial and legal problems, family
      issues, and other stressors on farms that are correlated with accidents, on-the
      job injuries, disability, and harm to self or others. EAPs specifically have been
      shown to reduce on-the-job injuries by reducing employee stress. Ultimately the
      program has seen good usage commensurate with that at any place of employment.
      Further, in addition to seeking help for themselves, a number of farmers have
      used this management consultation service to obtain assistance with farm worker
      issues. Although the authors have not systematically studied this approach, it
      shows promise and the authors encourage its duplication and further study in
      other states.

PMID- 24911686
TI  - Improving eye safety in citrus harvest crews through the acceptance of personal
      protective equipment, community-based participatory research, social marketing,
      and community health workers.
AB  - For the last 10 years, the Partnership for Citrus Workers Health (PCWH) has been
      an evidence-based intervention program that promotes the adoption of protective
      eye safety equipment among Spanish-speaking farmworkers of Florida. At the root
      of this program is the systematic use of community-based preventive marketing
      (CBPM) and the training of community health workers (CHWs) among citrus harvester
      using popular education. CBPM is a model that combines the organizational system
      of community-based participatory research (CBPR) and the strategies of social
      marketing. This particular program relied on formative research data using a
      mixed-methods approach and a multilevel stakeholder analysis that allowed for
      rapid dissemination, effective increase of personal protective equipment (PPE)
      usage, and a subsequent impact on adoptive workers and companies. Focus groups,
      face-to-face interviews, surveys, participant observation, Greco-Latin square,
      and quasi-experimental tests were implemented. A 20-hour popular education
      training produced CHWs that translated results of the formative research to
      potential adopters and also provided first aid skills for eye injuries. Reduction
      of injuries is not limited to the use of safety glasses, but also to the adoption
      of timely intervention and regular eye hygiene. Limitations include adoption in
      only large companies, rapid decline of eye safety glasses without consistent
      intervention, technological limitations of glasses, and thorough cost-benefit
      analysis.

PMID- 24911687
TI  - Improving health and safety conditions in agriculture through professional
      training of Florida farm labor supervisors.
AB  - Because farm labor supervisors (FLSs) are responsible for ensuring safe work
      environments for thousands of workers, providing them with adequate knowledge is
      critical to preserving worker health. Yet a challenge to offering professional
      training to FLSs, many of whom are foreign-born and have received different
      levels of education in the US and abroad, is implementing a program that not only
      results in knowledge gains but meets the expectations of a diverse audience. By
      offering bilingual instruction on safety and compliance, the University of
      Florida Institute of Food and Agricultural Sciences (UF/IFAS) FLS Training
      program is helping to improve workplace conditions and professionalize the
      industry. A recent evaluation of the program combined participant observation and
      surveys to elicit knowledge and satisfaction levels from attendees of its fall
      2012 trainings. Frequency distributions and dependent- and independent-means t
      tests were used to measure and compare participant outcomes. The evaluation found
      that attendees rated the quality of their training experience as either high or
      very high and scored significantly better in posttraining knowledge tests than in
      pretraining knowledge tests across both languages. Nonetheless, attendees of the
      trainings delivered in English had significantly higher posttest scores than
      attendees of the trainings delivered in Spanish. As a result, the program has
      incorporated greater standardization of content delivery and staff development.
      Through assessment of its program components and educational outcomes, the
      program has documented its effectiveness and offers a replicable approach that
      can serve to improve the targeted outcomes of safety and health promotion in
      other states.

PMID- 24911688
TI  - Family services for migrant and seasonal farm workers: the Redlands Christian
      Migrant Association (RCMA) model.
AB  - Agricultural employers and work supervisors strive to keep children out of
      worksites, but oftentimes migrating farm worker parents lack accessible or
      affordable options for childcare in a trusted environment. Thus, children may not
      have a safe, appropriate place to be while their parents are conducting
      agricultural work. Redlands Christian Migrant Association (RCMA) of Florida is a
      community development organization that creates and fosters opportunities for the
      children of migrant and other low-income rural families. To better understand the
      RCMA system, an in-depth assessment of its program was undertaken to identify
      both its standard and unique features. Results revealed many attributes
      contributing to RCMA's success. Based upon RCMA's 48-year track record,
      employers, agribusinesses, and communities are encouraged to adopt strategies to
      meet local and regional childcare needs where parents are working in agriculture.

PMID- 24911690
TI  - Latino migrant farmworker student development of safety instructional videos for
      peer education.
AB  - The purpose of this community-based study was to test effectiveness of a peer
      education safety education program that included student-produced videos and
      photovoice, nested in a 7-week summer Migrant Education Program. The second aim
      was to evaluate psychometrics of an adapted safety survey from Westaby and Lee
      used to evaluate changes in safety knowledge and attitudes. This was a one-group
      pre/post design intervention study. The convenience sample was Latino migrant
      students (N=117, middle school [grades 6-8, n=37], lower school [grades 3-5,
      n=80]), with data collected at baseline and post-intervention. Participants were
      male n=59, female n=58. Nine student safety videos were created by the middle
      schoolers who presented safety to the lower school. There were no statistically
      significant results comparing pre/post median subscale scores but results showed
      increased safety knowledge and there was a slight increase in injury experience.
      Wilcoxon Signed Rank Tests split for middle versus lower school showed
      statistical difference in middle school students over lower school students
      (P=.054) in safety knowledge. Kruskal Wallis analysis by gender showed
      statistical differences in medians in safety consciousness (chi2=5.949, df 1,
      P=.015); dangerous risk-taking (chi2=5.409, df 1, P=.020). There were positive
      significant associations between age and dangerous risk taking participation;
      safety consciousness and dangerous risk taking; safety knowledge with safety
      activity participation; and safety activities with safety consciousness. Survey
      showed 0.69% random missing data. Cronbach's alphas ranged .689-.863. Future
      research needs to review lessons learned and replication with larger samples.

PMID- 24911689
TI  - Safety and health hazard observations in Hmong farming operations.
AB  - Agricultural workers have a high risk of occupational injuries, illnesses, and
      fatalities. However, there are very few standardized tools available to assess
      safety and health in agricultural operations. Additionally, there are a number of
      groups of agricultural workers, including Hmong refugees and immigrants, for
      which virtually no information on safety and health conditions is available. This
      study developed an observation-based methodology for systematically evaluating
      occupational health and safety hazards in agriculture, and pilot-tested this on
      several small-scale Hmong farming operations. Each observation assessed of range
      of safety and health hazards (e.g., musculoskeletal hazards, dust and pollen,
      noise, and mechanical hazards), as well as on factors such as type of work area,
      presence of personal protective equipment, and weather conditions. Thirty-six
      observations were collected on nine farms. The most common hazards observed were
      bending at the back and lifting <50 pounds. Use of sharp tools without adequate
      guarding mechanisms, awkward postures, repetitive hand motions, and lifting >50
      pounds were also common. The farming activities observed involved almost no power
      equipment, and no pesticide or chemical handling was observed. The use of
      personal protective equipment was uncommon. The results of this assessment agreed
      well with a parallel study of perceived safety and health hazards among Hmong
      agricultural workers. This study suggests that small-scale Hmong farming
      operations involve a variety of hazards, and that occupational health
      interventions may be warranted in this community. The study also demonstrates the
      utility of standardized assessment tools and mixed-method approaches to hazard
      evaluation.

PMID- 24911691
TI  - Evaluation of respiratory symptoms and respiratory protection behavior among
      poultry workers in small farming operations.
AB  - Agricultural workers who work in enclosed poultry operations are at increased
      risk of respiratory exposure to atmospheric contaminants, including dusts,
      endotoxins, particulate from feathers, ammonia, and hydrogen sulfide from animal
      excrement. Given the relatively large number of small, family-run poultry farms
      in North Carolina, there has been relatively little research in the area
      documenting human lung function and perception of using respiratory protection
      among poultry workers. This study assesses respiratory health, knowledge, and
      perception of wearing respiratory protection among a sample of poultry workers
      attending a regional farm show in North Carolina. Lung function (spirometry),
      airway inflammation (exhaled nitric oxide), self-reported respiratory symptoms,
      and behavior of wearing respiratory protection were evaluated. Overall, mean lung
      function values were slightly lower than normal predicted values. The majority of
      participants ranked using respiratory protection as very important (51.9%);
      however, actual self-reported behavior was low (16.7%). In bivariate analysis,
      associations between the importance of wearing respiratory protection and the
      number of poultry houses (P=.04), as well as using a respirator and the number of
      poultry houses (P=.01) were statistically significant. Improved educational
      opportunities, including fit-testing and proper respiratory selection, should be
      emphasized for workers at small, poultry farm operations.

PMID- 24911692
TI  - Ocular health assessment of cocoa farmers in a rural community in Ghana.
AB  - Cocoa farming provides employment for over 800,000 households in rural Ghana,
      with the country currently touted as the second largest producer of cocoa
      worldwide. Agriculture is one of the riskiest occupations for the eyes due to the
      numerous ocular hazards on farms. The authors conducted an ocular health
      assessment among cocoa farmers at Mfuom, a rural community in the Central Region
      of Ghana, to examine the ocular health status and the ocular safety measures used
      by cocoa farmers. A structured questionnaire was used to evaluate demographic
      characteristics, ocular injuries, and utilization of eye care services and ocular
      protection, and a clinical examination was used to evaluate their ocular status.
      Cocoa farmers were at high risk for ocular injuries and farm-related vision
      disorders and utilized eye care services and ocular protection poorly. Ocular
      condition identified were mainly refractive error (28.6%), cataract (20.0%),
      glaucoma (11.7%), conjunctivitis (13%), pterygium (2.7%), and cornea opacity
      (2.2%). There is a need for the introduction of an interventional eye care
      program to help address the ocular health challenges identified among the
      farmers. This can be done through collaborative efforts by educational
      institutions, government, and other role players in the agricultural industry to
      improve the quality of life of the vulnerable cocoa farmers in rural Ghana.

PMID- 24911693
TI  - The lived experience of low back pain among Irish farmers: case studies.
AB  - Low back pain (LBP) is the most commonly reported musculoskeletal disorder (MSD)
      among farmers. There is limited researching regarding the lived experience of LBP
      among farmers. Video interviews were conducted with three dairy farmers who
      reported having a significant episode of LBP. The interview data were transcribed
      and analyzed, and results were presented in relation to the constructs explored.
      The farmers experienced their first significant episode of LBP in their late 20s
      or early 30s and all attributed their LBP to farm work or a farm-related
      incident. Hours worked per day ranged from 9 to 13 hours. Tasks identified by
      farmers that they were unable to do due to LBP included physical work, working
      with sheep, building work, and "certain jobs." Work changes made due to LBP
      included getting help, slowing down, avoiding strenuous work, carrying smaller
      loads, mechanizing the farm, using the tractor more, and wearing a back belt for
      certain jobs. Each farmer had his own way of preventing or managing his LBP,
      including a mix of active self-management and passive coping strategies such as
      swimming, using ice, spinal manipulation, and taking medication. The farmers were
      unable to quantify how much their LBP had cost them directly or indirectly. The
      case studies illustrate farmers engaging in ongoing work despite significant
      pain. All of the farmers have adapted at work and engaged in self-management
      strategies to reduce the occurrence of LBP. Given the rich data produced by these
      case studies, future case studies are recommended to gain greater insights into
      farmers' experiences concerning LBP.

PMID- 24911694
TI  - North Carolina farm women: opportunities for support and farm-related education.
AB  - The stress that farming visits upon male farmers has been acknowledged for
      decades. Stress- and work-related injuries among nonmigrant farm women is well
      documented from 1980 through the mid-1990s. A void of literature concerning
      nonmigrant farm women exists since that time. One possible explanation for this
      deficit is that United States Department of Agriculture Census of Agriculture
      data only consider the contributions of women on the farm if they are reported as
      farm operators. From 2002 to 2007, the number of women farm operators in North
      Carolina (NC) increased by 3%, and currently 13% of the state's farms are
      operated by women. These numbers emphasize the importance of understanding the
      self-perceived needs of women farmers. A qualitative research project was
      conducted to investigate the social-emotional needs of NC farm women.
      Semistructured interviews were conducted with 15 women with whom the NC
      Agromedicine Institute had previously worked in collaboration on farm health and
      safety. Key themes from interviews were (1) chameleonic, (2) inseparable
      connectedness, (3) farm sword, (4) women of a feather, and (5) one size doesn't
      fit all. Participants reported multiple roles, difficulty separating from the
      farm, preferring the farm over any other place, and viewing themselves as
      misperceived farm professionals. Participants need opportunities to interact with
      other farm women for support and sharing farm-management techniques. Future study
      recommendations include (1) inventory existing programs for farm women; (2)
      further investigate the support and educational needs of farm women; and (3)
      examine how farm women are perceived by nonfarm individuals.

PMID- 24911767
TI  - Air-stable electron depletion of Bi(2)Se(3) using molybdenum trioxide into the
      topological regime.
AB  - We perform high-resolution photoelectron spectroscopy on in situ cleaved
      topological insulator Bi2Se3 single crystals and in situ transport measurements
      on Bi2Se3 films grown by molecular beam epitaxy. We demonstrate efficient
      electron depletion of Bi2Se3 via vacuum deposition of molecular MoO3, lowering
      the surface Fermi energy to within ~100 meV of the Dirac point, well into the
      topological regime. A 100 nm MoO3 film provides an air-stable doping and
      passivation layer. 

PMID- 24911768
TI  - Turning unreactive copper acetylides into remarkably powerful and mild alkyne
      transfer reagents by oxidative umpolung.
AB  - This is not breaking news: copper acetylides, readily available polymeric rock
      stable solids, have been known for more than a century to be unreactive species
      and piteous nucleophiles. This lack of reactivity actually makes them ideal
      alkyne transfer reagents that can be easily activated under mild oxidizing
      conditions. When treated with molecular oxygen in the presence of simple
      chelating nitrogen ligands such as TMEDA, phenanthroline or imidazole
      derivatives, they are smoothly oxidized to highly electrophilic species that
      formally behave like acetylenic carbocations and can therefore be used for the
      mild and practical alkynylation of a wide range of nitrogen, phosphorus and
      carbon nucleophiles. 

PMID- 24911769
TI  - Safely examining complex dynamics of intimate partner violence.
AB  - The overall goal of this study is to use complexity science to gain a deeper
      understanding of the nonlinear day-to-day dynamics of intimate partner violence,
      with implications for clinical interventions. This report describes research
      methods for gathering information about partner violence in real time and
      assesses recruitment and retention, adherence to study protocol, data validity,
      and participant safety. Research assistants enrolled 200 women in moderately
      violent intimate relationships and asked them to report about their relationships
      every day for 12 weeks. Daily, participants telephoned an Interactive Voice
      Response (IVR) system and responded to 34 survey questions. They also completed
      baseline and end-of-study surveys and maintained telephone contact with the study
      team weekly. Forty-two participants completed qualitative end-of-study interviews
      to describe their relationships and the impact of the study on their lives. Of
      200 enrollees, 145 women provided enough data for nonlinear analyses, averaging
      63.5 daily reports of 84 possible. Participants submitted 9,201 daily reports,
      documenting partner's verbal or physical aggression on 39.4% of days, and their
      own aggression on 23.1%. Two women were withdrawn from the study for safety
      reasons; the remainder reported that study participation posed no additional
      threat. Eighty women sought assistance from community resources. Violence
      severity did not appear to change over the 12 weeks. The research team
      successfully and safely recruited and retained 145 women who provided valuable
      data for a study of complex dynamics of intimate partner violence.

PMID- 24911770
TI  - Managing the health care needs of adolescents with autism spectrum disorder: the
      parents' experience.
AB  - Parents of adolescents with autism spectrum disorder (ASD) experience the
      challenges of navigating the health care system, locating information about ASD,
      lacking an understanding of prescribed medications, and experiencing minimal
      social support from health care providers. The purpose of this phenomenological
      study was to describe the experiences of parents who manage the health needs of
      an adolescent with ASD. Qualitative interviews were conducted at a university
      setting with 12 parents of 10 adolescents with ASD residing in Central Virginia.
      Data were analyzed using Moustakas' method in which the phenomenologist asks the
      following questions: What are the individual's experiences and in what context
      did they experience them? This study maximized credibility using 3 strategies:
      prolonged engagement, peer debriefing, and member checking. "Parents needing
      assistance" emerged as the essence of the parents' experiences. Four themes
      representing the essential challenging elements of the parents' experiences
      included concern with medications, frustrations with health care services,
      recognizing secondary health issues, and the need for resources and services.
      Findings of the current study revealed key factors to be considered in the
      development and delivery of health care for adolescents with ASD. These include
      creating and planning interventions for parents, sharing information about
      resources and services, and collaborating with others in the health care field.
      Additional research, both qualitative and quantitative, is needed to understand
      how parents and adolescents with ASD experience this transitional period.

PMID- 24911771
TI  - Tissue distribution, bioconcentration, metabolism, and effects of erythromycin in
      crucian carp (Carassius auratus).
AB  - In this study, the tissue distribution, bioconcentration, metabolism and
      biological effects of the macrolide antibiotic erythromycin (ERY) were
      investigated in fish using crucian carp (Carassius auratus) as a model. Crucian
      carp were exposed to various concentrations of ERY (4, 20, and 100 MUg/L) for 28
      days. The UPLC/MS/MS analysis of both water and tissue provided the
      bioconcentration of ERY and its metabolites in the fish body. The results from
      tissue samples showed that a maximum tissue concentration occurred in the muscle
      and that the bioconcentration factor (BCF) of 72.2 was lower than the theoretical
      BCF of 90.4 calculated from the octanol-water coefficient of ERY. A significant
      portion of the absorbed ERY was metabolized via demethylation and dehydration and
      observed in the form of descladinose in fish. In addition, the relevant
      biomarkers, including acetylcholinesterase in the brain, as well as 7
      ethoxyresorufin O-deethylase and superoxide dismutase in the liver, changed
      significantly during 28 days of exposure (P<0.05). These results clearly
      indicated that ERY accumulated in fish and that similar metabolites as those
      observed in mammals were produced, resulting in the biochemical disturbance of
      biological systems.

PMID- 24911772
TI  - Impact of management strategies on the global warming potential at the cropping
      system level.
AB  - Estimating the greenhouse gas (GHG) emissions from agricultural systems is
      important in order to assess the impact of agriculture on climate change. In this
      study experimental data supplemented with results from a biophysical model (DNDC)
      were combined with life cycle assessment (LCA) to investigate the impact of
      management strategies on global warming potential of long-term cropping systems
      at two locations (Breton and Ellerslie) in Alberta, Canada. The aim was to
      estimate the difference in global warming potential (GWP) of cropping systems due
      to N fertilizer reduction and residue removal. Reducing the nitrogen fertilizer
      rate from 75 to 50 kg N ha(-1) decreased on average the emissions of N2O by 39%,
      NO by 59% and ammonia volatilisation by 57%. No clear trend for soil CO2
      emissions was determined among cropping systems. When evaluated on a per hectare
      basis, cropping systems with residue removal required 6% more energy and had a
      little change in GWP. Conversely, when evaluated on the basis of gigajoules of
      harvestable biomass, residue removal resulted in 28% less energy requirement and
      33% lower GWP. Reducing nitrogen fertilizer rate resulted in 18% less GWP on
      average for both functional units at Breton and 39% less GWP at Ellerslie.
      Nitrous oxide emissions contributed on average 67% to the overall GWP per ha.
      This study demonstrated that small changes in N fertilizer have a minimal impact
      on the productivity of the cropping systems but can still have a substantial
      environmental impact.

PMID- 24911773
TI  - Impact of catchment geophysical characteristics and climate on the regional
      variability of dissolved organic carbon (DOC) in surface water.
AB  - Dissolved organic carbon (DOC) is a recognized indicator of natural organic
      matter (NOM) in surface waters. The aim of this paper is twofold: to evaluate the
      impact of geophysical characteristics, climate and ecological zones on DOC
      concentrations in surface waters and, to develop a statistical model to estimate
      the regional variability of these concentrations. In this study, multilevel
      statistical analysis was used to achieve three specific objectives: (1) evaluate
      the influence of climate and geophysical characteristics on DOC concentrations in
      surface waters; (2) compare the influence of geophysical characteristics and
      ecological zones on DOC concentrations in surface waters; and (3) develop a model
      to estimate the most accurate DOC concentrations in surface waters. The case
      study involved 115 catchments from surface waters in the Province of Quebec,
      Canada. Results showed that mean temperatures recorded 60 days prior to sampling,
      total precipitation 10 days prior to sampling and percentages of wetlands,
      coniferous forests and mixed forests have a significant positive influence on DOC
      concentrations in surface waters. The catchment mean slope had a significant
      negative influence on DOC concentrations in surface waters. Water type (lake or
      river) and deciduous forest variables were not significant. The ecological zones
      had a significant influence on DOC concentrations. However, geophysical
      characteristics (wetlands, forests and slope) estimated DOC concentrations more
      accurately. A model describing the variability of DOC concentrations was
      developed and can be used, in future research, for estimating DBPs in drinking
      water as well evaluating the impact of climate change on the quality of surface
      waters and drinking water.

PMID- 24911774
TI  - 2001-2012 trends on air quality in Spain.
AB  - This study aims at interpreting the 2001-2012 trends of major air pollutants in
      Spain, with a major focus on evaluating their relationship with those of the
      national emission inventories (NEI) and policy actions. Marked downward
      concentration trends were evidenced for PM10, PM2.5 and CO. Concentrations of NO2
      and NOx also declined but in a lesser proportion at rural and traffic sites. At
      rural sites O3 has been kept constant, whereas it clearly increased at urban and
      industrial sites. Comparison of the air quality trends and major inflection
      points with those from NEIs, the National Energy Consumption and the calendar of
      the implementation of major policy actions allowed us to clearly identify major
      benefits of European directives on power generation and industrial sources (such
      as the Large Combustion Plants and the Integrated Pollution Prevention and
      Control Directives). This, together with a sharp 2007-2008 decrease of coal
      consumption has probably caused the marked parallel decline of SO2, NOx and for
      PM2.5 concentrations. Also the effect of the EURO 4 and 5 vehicle emission
      standards on decreasing emissions of PM and CO from vehicles is noticeable. The
      smooth decline in NO2-NOx levels is mostly attributed to the low efficiency of
      EURO 4 and 5 standards in reducing real life urban driving NO2 emissions. The low
      NOx decrease together with the complexity of the reactions of O3 formation is
      responsible for the constant O3 concentrations, or even the urban increase. The
      financial crisis has also contributed to the decrease of the ambient
      concentration of pollutants; however this caused a major reduction of the primary
      energy consumption from 2008 to 2009, and not from 2007 to 2008 when ambient air
      PM and SO2 sharply decreased. The meteorological influence was characterized by a
      2008-2012 period favorable to the dispersion of pollutants when compared to the
      2001-2007. 

PMID- 24911775
TI  - Concentrations of halogenated natural products versus PCB 153 in bivalves from
      the North and Baltic Seas.
AB  - Different halogenated natural products (HNPs) have been reported to occur in
      marine wildlife, particularly from regions with comparably little contamination
      with anthropogenic pollutants. The North Sea and the Baltic Sea have been known
      as a marine site heavily polluted with organohalogen compounds, and especially
      with polychlorinated biphenyls (PCBs). In this study we wished to determine the
      current abundance of HNPs in comparison with 2,2',4,4',5,5'-hexachlorobiphenyl
      (PCB 153), i.e. the major PCB congener in marine biota. For this purpose, forty
      blue mussels (Mytilus edulis) and oysters (Crassostrea gigas) from seven sites
      were analyzed on HNPs and PCB 153. Most of the samples contained HNPs in the form
      of polyhalogenated 1'-methyl-1,2'-bipyrroles (PMBPs including Q1) and the mixed
      halogenated compound MHC-1. In addition we determined several polyhalogenated
      1,1'-dimethyl-2,2'-bipyrroles (PDBPs), 2,3,4,5-tetrabromo-N-methylpyrrole and
      several novel homologs, as well as polybrominated N-methylindoles. The occurrence
      of these HNP groups were considerably different in the samples from different
      regions with varying sum concentrations up to 1930 MUg/kg lipids in blue mussels
      from Heligoland (North Sea) and much lower concentrations in samples from the
      Baltic Sea (up to 13 MUg/kg lipids). The concentrations of HNPs varied by two
      orders of magnitude, compared to a factor of 10 for PCB 153, suggesting that HNPs
      are more spatially (and perhaps temporally) variant than POPs. In the North Sea
      region Heligoland, HNPs were more abundant than PCB 153.

PMID- 24911776
TI  - Organochlorine pesticide levels in maternal serum and risk of neural tube defects
      in offspring in Shanxi Province, China: a case-control study.
AB  - Organochlorine pesticides (OCPs) in placental tissue have been reported to be
      associated with an increased risk for fetal neural tube defects (NTDs). Our case
      control study was performed to explore the association between maternal serum OCP
      concentration and NTD risk in offspring. Serum samples were collected from 117
      mothers who delivered NTD infants (case group) and 121 mothers who delivered
      healthy infants (control group). Only three of the 25 OCPs were detected in more
      than half of the maternal serum samples. The median concentration of total OCPs
      in the case group was significantly higher than that of the control group.
      However, no dose-response relationships between higher levels of any individual
      OCPs or total OCPs and the risk of NTDs or subtypes were observed in either the
      unadjusted binary unconditional logistic regression model or the model adjusted
      by potential confounders. We conclude that no clear association between maternal
      serum OCP residues and NTD risk in offspring was observed in this population.
      CAPSULE: No clear association between maternal serum levels of organochlorine
      pesticides and risk of neural tube defects in offspring was observed for a
      Chinese population.

PMID- 24911778
TI  - The effect of clumped population structure on the variability of spreading
      dynamics.
AB  - Processes that spread through local contact, including outbreaks of infectious
      diseases, are inherently noisy, and are frequently observed to be far noisier
      than predicted by standard stochastic models that assume homogeneous mixing. One
      way to reproduce the observed levels of noise is to introduce significant
      individual-level heterogeneity with respect to infection processes, such that
      some individuals are expected to generate more secondary cases than others. Here
      we consider a population where individuals can be naturally aggregated into
      clumps (subpopulations) with stronger interaction within clumps than between
      them. This clumped structure induces significant increases in the noisiness of a
      spreading process, such as the transmission of infection, despite complete
      homogeneity at the individual level. Given the ubiquity of such clumped
      aggregations (such as homes, schools and workplaces for humans or farms for
      livestock) we suggest this as a plausible explanation for noisiness of many
      epidemic time series. 

PMID- 24911777
TI  - Pathway and network analysis in proteomics.
AB  - Proteomics is inherently a systems science that studies not only measured protein
      and their expressions in a cell, but also the interplay of proteins, protein
      complexes, signaling pathways, and network modules. There is a rapid accumulation
      of Proteomics data in recent years. However, Proteomics data are highly variable,
      with results sensitive to data preparation methods, sample condition, instrument
      types, and analytical methods. To address the challenge in Proteomics data
      analysis, we review current tools being developed to incorporate biological
      function and network topological information. We categorize these tools into four
      types: tools with basic functional information and little topological features
      (e.g., GO category analysis), tools with rich functional information and little
      topological features (e.g., GSEA), tools with basic functional information and
      rich topological features (e.g., Cytoscape), and tools with rich functional
      information and rich topological features (e.g., PathwayExpress). We first review
      the potential application of these tools to Proteomics; then we review tools that
      can achieve automated learning of pathway modules and features, and tools that
      help perform integrated network visual analytics. 

PMID- 24911779
TI  - Social foraging with partial (public) information.
AB  - Group foragers can utilize public information to better estimate patch quality
      and arrive at more efficient patch-departure rules. However, acquiring such
      information may come at a cost; e.g. reduced search efficiency. We present a
      Bayesian group-foraging model in which social foragers do not require full
      awareness of their companions' foraging success; only of their number. In our
      model, patch departure is based on direct estimates of the number of remaining
      items. This is achieved by considering all likely combinations of initial patch
      quality and group foraging-success; given the individual forager's experience
      within the patch. Slower rates of information-acquisition by our 'partially
      aware' foragers lead them to over-utilize poor patches; more than fully-aware
      foragers. However, our model suggests that the ensuing loss in long-term intake
      rates can be matched by a relatively low cost to the acquisition of full public
      information. In other words, we suggest that group-size offers sufficient
      information for optimal patch utilization by social foragers. We suggest, also,
      that our model is applicable to other situations where resources undergo
      'background depletion', which is coincident but independent of the consumer's own
      utilization. 

PMID- 24911780
TI  - A measure of DNA sequence similarity by Fourier Transform with applications on
      hierarchical clustering.
AB  - Multiple sequence alignment (MSA) is a prominent method for classification of DNA
      sequences, yet it is hampered with inherent limitations in computational
      complexity. Alignment-free methods have been developed over past decade for more
      efficient comparison and classification of DNA sequences than MSA. However, most
      alignment-free methods may lose structural and functional information of DNA
      sequences because they are based on feature extractions. Therefore, they may not
      fully reflect the actual differences among DNA sequences. Alignment-free methods
      with information conservation are needed for more accurate comparison and
      classification of DNA sequences. We propose a new alignment-free similarity
      measure of DNA sequences using the Discrete Fourier Transform (DFT). In this
      method, we map DNA sequences into four binary indicator sequences and apply DFT
      to the indicator sequences to transform them into frequency domain. The Euclidean
      distance of full DFT power spectra of the DNA sequences is used as similarity
      distance metric. To compare the DFT power spectra of DNA sequences with different
      lengths, we propose an even scaling method to extend shorter DFT power spectra to
      equal the longest length of the sequences compared. After the DFT power spectra
      are evenly scaled, the DNA sequences are compared in the same DFT frequency space
      dimensionality. We assess the accuracy of the similarity metric in hierarchical
      clustering using simulated DNA and virus sequences. The results demonstrate that
      the DFT based method is an effective and accurate measure of DNA sequence
      similarity. 

PMID- 24911781
TI  - RNA editing and modifications of RNAs might have favoured the evolution of the
      triplet genetic code from an ennuplet code.
AB  - Here we suggest that the origin of the genetic code, that is to say, the birth of
      first mRNAs has been triggered by means of a widespread modification of all RNAs
      (proto-mRNAs and proto-tRNAs), as today observed in the RNA editing and in post
      transcriptional modifications of RNAs, which are considered as fossils of this
      evolutionary stage of the genetic code origin. We consider also that other
      mechanisms, such as the trans-translation and ribosome frameshifting, could have
      favoured the transition from an ennuplet code to a triplet code. Therefore,
      according to our hypothesis all these mechanisms would be reflexive of this
      period of the evolutionary history of the genetic code. 

PMID- 24911782
TI  - Entrainment to a real time fractal visual stimulus modulates fractal gait
      dynamics.
AB  - Fractal patterns characterize healthy biological systems and are considered to
      reflect the ability of the system to adapt to varying environmental conditions.
      Previous research has shown that fractal patterns in gait are altered following
      natural aging or disease, and this has potential negative consequences for gait
      adaptability that can lead to increased risk of injury. However, the flexibility
      of a healthy neurological system to exhibit different fractal patterns in gait
      has yet to be explored, and this is a necessary step toward understanding human
      locomotor control. Fifteen participants walked for 15min on a treadmill, either
      in the absence of a visual stimulus or while they attempted to couple the timing
      of their gait with a visual metronome that exhibited a persistent fractal pattern
      (contained long-range correlations) or a random pattern (contained no long-range
      correlations). The stride-to-stride intervals of the participants were recorded
      via analog foot pressure switches and submitted to detrended fluctuation analysis
      (DFA) to determine if the fractal patterns during the visual metronome conditions
      differed from the baseline (no metronome) condition. DFA alpha in the baseline
      condition was 0.77+/-0.09. The fractal patterns in the stride-to-stride intervals
      were significantly altered when walking to the fractal metronome (DFA
      alpha=0.87+/-0.06) and to the random metronome (DFA alpha=0.61+/-0.10) (both
      p<.05 when compared to the baseline condition), indicating that a global change
      in gait dynamics was observed. A variety of strategies were identified at the
      local level with a cross-correlation analysis, indicating that local behavior did
      not account for the consistent global changes. Collectively, the results show
      that a gait dynamics can be shifted in a prescribed manner using a visual
      stimulus and the shift appears to be a global phenomenon. 

PMID- 24911783
TI  - Successful conservative management of traumatic post-coital recto-neovaginal
      fistula in male-to-female transsexual.

PMID- 24911784
TI  - The decline in gross efficiency in relation to cycling time-trial length.
AB  - PURPOSE: To evaluate whether gross efficiency (GE), determined during submaximal
      cycling, is lower after time trials and if the magnitude of the decrease differs
      in relation to race distance. Secondary purposes were to study the rate of the
      decline in GE and whether changes in muscle-fiber recruitment could explain the
      decline. METHODS: Cyclists completed 9 GE tests consisting of submaximal exercise
      performed before and after time trials of different length (500 m, 1000 m, 2000
      m, 4000 m, 15,000 m, and 40,000 m). In addition, subjects performed time trials
      as if they were a 1000-m, 4000-m, or 40,000-m time trial during which they were
      stopped at 50% of the final time of the preceding "full" time trial. Power
      output, gas exchange, and EMG were measured continuously throughout the GE tests.
      RESULTS: A significant interaction effect between distance and time was found for
      GE (P = .001). GE was significantly lower immediately after the time trials than
      before (P < .05), and the decline in GE differed between distances (P < .001). GE
      seemed to decline linearly during the relatively short trials, while it declined
      more hyperbolically during the 40,000-m. A significant effect of time (P = .04)
      on mean EMG amplitude was found. However, post hoc comparisons showed no
      significant differences in mean EMG amplitude between the different time points
      (before and after the time trials). CONCLUSION: GE decreases during time-trial
      exercise. Unfortunately, the cause of the decrease remains uncertain. Future
      modeling studies should consider using a declining instead of a constant GE. In
      sport situations, the declining GE has to be taken into account when selecting a
      pacing strategy.

PMID- 24911785
TI  - Mitotic entry elucidated with bacterial toxin toolbox.

PMID- 24911786
TI  - Configuring the mesh size, side taper and wing depth of penaeid trawls to reduce
      environmental impacts.
AB  - The effects of reducing mesh size while concomitantly varying the side taper and
      wing depth of a generic penaeid-trawl body were investigated to improve
      engineering performance and minimize bycatch. Five trawl bodies (with the same
      codends) were tested across various environmental (e.g. depth and current) and
      biological (e.g. species and sizes) conditions. The first trawl body comprised 41
      mm mesh and represented conventional designs (termed the '41 long deep-wing'),
      while the remaining trawl bodies were made from 32-mm mesh and differed only in
      their side tapers, and therefore length (i.e. 1N3B or 'long' and ~28o to the tow
      direction vs 1N5B or 'short' and ~35o) and wing depths ('deep'-97 T vs 'shallow'
      60 T). There were incremental drag reductions (and therefore fuel savings--by up
      to 18 and 12% per h and ha trawled) associated with reducing twine area via
      either modification, and subsequently minimizing otter-board area in attempts to
      standardize spread. Side taper and wing depth had interactive and varied effects
      on species selectivity, but compared to the conventional 41 long deep-wing trawl,
      the 32 short shallow-wing trawl (i.e. the least twine area) reduced the total
      bycatch by 57% (attributed to more fish swimming forward and escaping). In most
      cases, all small-meshed trawls also caught more smaller school prawns Metapenaeus
      macleayi but to decrease this effect it should be possible to increase mesh size
      slightly, while still maintaining the above engineering benefits and species
      selectivity. The results support precisely optimizing mesh size as a precursor to
      any other anterior penaeid-trawl modifications designed to improve environmental
      performance.

PMID- 24911788
TI  - Quantitative measurement of organic acids in tissues from gastric cancer patients
      indicates increased glucose metabolism in gastric cancer.
AB  - The levels of organic acids representing metabolic pathway end products are
      important indicators of physiological status, and may be associated with
      metabolic changes in cancer. The aim of this study is to investigate the levels
      of organic acids in cancerous and normal tissues from gastric cancer patients and
      to confirm the role of metabolic alterations in gastric carcinogenesis. Organic
      acids in normal and cancerous tissues from forty-five patients with gastric
      adenocarcinoma were investigated by gas chromatography-mass spectrometry in
      selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We
      analysed the significant differences in the levels of organic acids in normal and
      cancer tissues and investigated the correlation of these levels in cancer tissues
      with clinicopathological features. The levels of Krebs cycle components,
      including alpha-ketoglutaric acid, succinic acid, fumaric acid, malic acid and
      oxaloacetic acid, were significantly increased in cancer tissues compared to
      normal tissues. In addition, the levels of glycolytic products, including pyruvic
      acid and lactic acid, as well as the levels of ketone bodies, including 3
      hydroxybutyric acid, were also significantly increased in cancer tissues compared
      to normal tissues. The levels of ketone bodies in cancer tissues with
      differentiated histology and in intestinal-type cancer tissues were significantly
      increased. The organic acid profiling analysis described here may be a generally
      useful clinical tool for understanding the complexity of metabolic events in
      gastric adenocarcinoma, and organic acids may have potential as metabolic markers
      for the future discovery of diagnostic and therapeutic modalities. 

PMID- 24911787
TI  - An improved model of heat-induced hyperalgesia--repetitive phasic heat pain
      causing primary hyperalgesia to heat and secondary hyperalgesia to pinprick and
      light touch.
AB  - This study tested a modified experimental model of heat-induced hyperalgesia,
      which improves the efficacy to induce primary and secondary hyperalgesia and the
      efficacy-to-safety ratio reducing the risk of tissue damage seen in other heat
      pain models. Quantitative sensory testing was done in eighteen healthy volunteers
      before and after repetitive heat pain stimuli (60 stimuli of 48 degrees C for 6
      s) to assess the impact of repetitive heat on somatosensory function in
      conditioned skin (primary hyperalgesia area) and in adjacent skin (secondary
      hyperalgesia area) as compared to an unconditioned mirror image control site.
      Additionally, areas of flare and secondary hyperalgesia were mapped, and time
      course of hyperalgesia determined. After repetitive heat pain conditioning we
      found significant primary hyperalgesia to heat, and primary and secondary
      hyperalgesia to pinprick and to light touch (dynamic mechanical allodynia).
      Acetaminophen (800 mg) reduced pain to heat or pinpricks only marginally by 11%
      and 8%, respectively (n.s.), and had no effect on heat hyperalgesia. In contrast,
      the areas of flare (-31%) and in particular of secondary hyperalgesia (-59%) as
      well as the magnitude of hyperalgesia (-59%) were significantly reduced (all
      p<0.001). Thus, repetitive heat pain induces significant peripheral sensitization
      (primary hyperalgesia to heat) and central sensitization (punctate hyperalgesia
      and dynamic mechanical allodynia). These findings are relevant to further studies
      using this model of experimental heat pain as it combines pronounced peripheral
      and central sensitization, which makes a convenient model for combined
      pharmacological testing of analgesia and anti-hyperalgesia mechanisms related to
      thermal and mechanical input. 

PMID- 24911789
TI  - CELLO2GO: a web server for protein subCELlular LOcalization prediction with
      functional gene ontology annotation.
AB  - CELLO2GO (http://cello.life.nctu.edu.tw/cello2go/) is a publicly available, web
      based system for screening various properties of a targeted protein and its
      subcellular localization. Herein, we describe how this platform is used to obtain
      a brief or detailed gene ontology (GO)-type categories, including subcellular
      localization(s), for the queried proteins by combining the CELLO localization
      predicting and BLAST homology-searching approaches. Given a query protein
      sequence, CELLO2GO uses BLAST to search for homologous sequences that are GO
      annotated in an in-house database derived from the UniProt KnowledgeBase
      database. At the same time, CELLO attempts predict at least one subcellular
      localization on the basis of the species in which the protein is found. When
      homologs for the query sequence have been identified, the number of terms found
      for each of their GO categories, i.e., cellular compartment, molecular function,
      and biological process, are summed and presented as pie charts representing
      possible functional annotations for the queried protein. Although the
      experimental subcellular localization of a protein may not be known, and thus not
      annotated, CELLO can confidentially suggest a subcellular localization. CELLO2GO
      should be a useful tool for research involving complex subcellular systems
      because it combines CELLO and BLAST into one platform and its output is easily
      manipulated such that the user-specific questions may be readily addressed. 

PMID- 24911790
TI  - Pathogen infection as a possible cause for autoimmune hepatitis.
AB  - Autoimmune disorders afflicting the liver comprise the bona fide autoimmune
      diseases, primary biliary cirrhosis, primary sclerosing cholangitis, and
      autoimmune hepatitis as well as drug-induced autoimmune-like diseases, such as
      halothane hepatitis. Whereas drug-induced forms of acute or chronic hepatitis
      often have a clear triggering factor, the etiology of classical autoimmune liver
      diseases is only poorly understood. Besides a genetic component present in
      disease susceptible individuals, environmental triggering factors are likely to
      play a role in the initiation and/or propagation of the disease. In this article,
      we will review on current evidence obtained from epidemiological associations,
      case studies, and findings in animal models for pathogens, to be involved in the
      etiology of autoimmune liver disease with a special focus on autoimmune
      hepatitis. 

PMID- 24911791
TI  - Oxazolone-induced contact hypersensitivity reduces lymphatic drainage but
      enhances the induction of adaptive immunity.
AB  - Contact hypersensitivity (CHS) induced by topical application of haptens is a
      commonly used model to study dermal inflammatory responses in mice. Several
      recent studies have indicated that CHS-induced skin inflammation triggers
      lymphangiogenesis but may negatively impact the immune-function of lymphatic
      vessels, namely fluid drainage and dendritic cell (DC) migration to draining
      lymph nodes (dLNs). On the other hand, haptens have been shown to exert immune
      stimulatory activity by inducing DC maturation. In this study we investigated how
      the presence of pre-established CHS-induced skin inflammation affects the
      induction of adaptive immunity in dLNs. Using a mouse model of oxazolone-induced
      skin inflammation we observed that lymphatic drainage was reduced and DC
      migration from skin to dLNs was partially compromised. At the same time, a
      significantly stronger adaptive immune response towards ovalbumin (OVA) was
      induced when immunization had occurred in CHS-inflamed skin as compared to
      uninflamed control skin. In fact, immunization with sterile OVA in CHS-inflamed
      skin evoked a delayed-type hypersensitivity (DTH) response comparable to the one
      induced by conventional immunization with OVA and adjuvant in uninflamed skin.
      Striking phenotypic and functional differences were observed when comparing DCs
      from LNs draining uninflamed or CHS-inflamed skin. DCs from LNs draining CHS
      inflamed skin expressed higher levels of co-stimulatory molecules and MHC
      molecules, produced higher levels of the interleukin-12/23 p40 subunit (IL-12/23
      p40) and more potently induced T cell activation in vitro. Immunization
      experiments revealed that blockade of IL-12/23-p40 during the priming phase
      partially reverted the CHS-induced enhancement of the adaptive immune response.
      Collectively, our findings indicate that CHS-induced skin inflammation generates
      an overall immune-stimulatory milieu, which outweighs the potentially suppressive
      effect of reduced lymphatic vessel function. 

PMID- 24911792
TI  - Ligation of CD47 induces G1 arrest in EBV-transformed B cells through ROS
      generation, p38 MAPK/JNK activation, and Tap73 upregulation.
AB  - CD47 is expressed in normal activated cells as well as in several tumors. It also
      has been implicated as having antiangiogenic and antimetastatic properties, but
      its roles in Epstein-Barr virus (EBV)-transformed B cells are still not fully
      understood. Herein, we report that EBV infection induced CD47 surface expression
      on B cells, and CD47 ligation with anti-CD47 mAb (B6H12) reduced cell
      proliferation and induced G1 arrest. CD47-induced G1 arrest was mediated through
      increased cyclin-dependent kinase inhibitors (CDKi) and a simultaneously
      decreased CDK/cyclins, and p38 MAPK/JNK activation preceded binding of CDKi-CDK.
      Moreover, reactive oxygen species (ROS) generation and upregulation of both TAp73
      and ER stress sensor proteins were detected after CD47 ligation, and p38
      inhibitor SB203580 and JNK inhibitor SP600125 blocked upregulation of TAp73 and
      cell cycle arrest. We investigated whether ROS generation is the initial event of
      CD47-mediated G1 arrest because ROS scavenger NAC effectively abrogated the
      majority of CD47-mediated responses but SB203580 and SP600125 did not block ROS
      production. Taken together, we concluded that CD47 ligation on EBV-transformed B
      cells led to G1 arrest by ROS generation and, subsequently, there was p38
      MAPK/JNK pathway activation, ER stress triggering, and TAp73 upregulation. Our
      findings provide data supporting CD47 as a feasible target for EBV-associated
      tumor therapy. 

PMID- 24911793
TI  - A comprehensive analysis of primary acute myeloid leukemia identifies biomarkers
      predicting susceptibility to human allogeneic Vgamma9Vdelta2 T cells.
AB  - Allogeneic innate lymphocytes such as Vgamma9Vdelta2 T cells are attractive
      candidates for cancer immunotherapy as they provide MHC-unrestricted antitumor
      activity without clinical evidence for inducing graft-versus-host disease (GvHD).
      However, current cellular immunotherapy approaches lack predictive biomarkers
      identifying patient cohorts most susceptible to immune attack. For this purpose
      we performed a comprehensive analysis of clinical, genetic, metabolic, and
      immunophenotypic features of 19 primary acute myeloid leukemia (AML) samples and
      correlated these factors with AML blast recognition by allogeneic Vgamma9Vdelta2
      T cells. We show that 36% of primary AML samples were intrinsically susceptible
      to allogeneic Vgamma9Vdelta2 T cells. Among several evaluated features, only UL
      16 binding protein 1 (ULBP1) expression (P<0.01) determines intrinsic AML
      susceptibility to allogeneic Vgamma9Vdelta2 T cells. Within the intrinsically
      resistant AML samples, pretreatment of AML blasts with nitrogen-containing
      bisphosphonates (NBP) significantly induced Vgamma9Vdelta2 T-cell cytotoxicity in
      50% of AML samples, whereas 50% of AML samples were consistently refractory to
      gammadelta T-cell cytolysis. Activity of the mevalonate pathway (P<0.05) and
      myelomonocytic differentiation of AML (P<0.05) correlated with sensitivity of
      primary AML samples toward NBP pretreatment. In conclusion, this study identifies
      subsets of AML patients most likely to benefit from allogeneic Vgamma9Vdelta2 T
      cell-mediated immunotherapy. 

PMID- 24911794
TI  - Profiles of activation, differentiation-markers, or beta-integrins on T cells
      contribute to predict T cells' antileukemic responses after stimulation with
      leukemia-derived dendritic cells.
AB  - Stem cell transplantations and donor lymphocyte infusions are promising
      immunotherapies to cure acute myeloid leukemia (AML). Leukemia-derived dendritic
      cells are known to improve antileukemic functionality of T cells. We evaluated
      the composition and development of distinct T-cell subtypes in AML patients
      (n=12) compared with healthy probands (n=5) before and during stimulation with
      leukemia-derived dendritic cells-containing DC (DC) or blast-containing
      mononuclear cells (MNC) in 0-7 days mixed lymphocyte cultures (MLC) by flow
      cytometry. AML patients' T-cell subgroups were correlated with antileukemic
      functionality before and after DC/MNC stimulation by functional fluorolysis
      assays. (1) Unstimulated T cells from AML patients presented with significantly
      lower proportions of activated, Tcm, CD137, and beta-integrin T cells, and
      significantly higher proportions of Tnaive and Teff compared with healthy
      probands. (2) After 7 days of DC or MNC stimulation, T-cell profiles were
      characterized by (significantly) increased proportions of activated T cells with
      effector function and significantly decreased proportions of beta-integrin T
      cells. (3) Antileukemic cytotoxicity was achieved in 40% of T cells after MNC
      stimulation compared with 64% after DC stimulation. Antileukemic activity after
      DC stimulation but not after MNC stimulation correlated with higher proportions
      of Tcm and Tnaive before stimulation, as well as with significantly higher
      proportions of activated and beta-integrin T cells. Furthermore, cutoff values
      for defined T-cell activation/differentiation markers and beta-integrin T cells
      could be defined, allowing a prediction of antileukemic reactivity. We could
      demonstrate the potential of the composition of unstimulated/DC-stimulated T
      cells for the lysis of AML blasts. Especially, AML patients with high numbers of
      Tnaive and Tcm could benefit from DC stimulation; proportions of activated and
      beta-integrin T cells correlated with increased antileukemic functionality and
      could serve to predict T cells' reactivity during stimulation. Refined analyses
      in the context of responses to immunotherapies are required. 

PMID- 24911795
TI  - Ipilimumab-induced autoimmune pancytopenia in a case of metastatic melanoma.
AB  - A 77-year-old patient treated with ipilimumab (anti-CTLA-4 antibody) for
      metastatic melanoma developed autoimmune pancytopenia (anemia, thrombocytopenia,
      and neutropenia) 8 days after the fourth infusion. This pancytopenia was
      resistant to high-dose oral corticosteroids (1 mg/kg) and to hematopoietic growth
      factors. It resolved after intravenous immunoglobulins injection. To date, only 1
      case of autoimmune pancytopenia has been reported after this treatment. According
      to the case that we report, it seems essential to control the leukocyte count
      before any injection of ipilimumab. 

PMID- 24911796
TI  - Iridium-catalyzed asymmetric hydrogenation of pyrrolo[1,2-a]pyrazinium salts.
AB  - Highly enantioselective iridium-catalyzed hydrogenation of pyrrolo[1,2
      a]pyrazinium salts has been achieved, providing a direct access to chiral 1,2,3,4
      tetrahydropyrrolo[1,2-a]pyrazine derivatives with up to 95% ee. The key feature
      of the reaction is the addition of cesium carbonate, which increases the
      conversion and prohibits the racemization pathway of products. 

PMID- 24911797
TI  - Endovascular treatment for primary aortic angiosarcoma to relieve thoracic aortic
      stenosis.
AB  - Aortic aneurysms and stenosis are widely treated with endovascular procedures in
      the current era. In this report, we present endovascular stent grafting for
      symptomatic treatment of severe thoracic aortic stenosis caused by an aortic
      sarcomatoid carcinoma in a 73-year-old female. The peri- and post-operative
      courses were complicated with tumor embolisms that were managed by both
      endovascular and surgical measures. 

PMID- 24911798
TI  - Chronic compartment syndrome secondary to venous hypertension: fasciectomy for
      symptom relief.
AB  - Chronic compartment syndrome (CCS) from venous hypertension following lower leg
      deep venous thrombosis or severe venous insufficiency is rare and often difficult
      to diagnose. Although ileocaval stenting and thrombolysis have improved
      claudication symptoms related to outflow venous disease, chronic calf
      claudication from distal vein thrombosis and venous insufficiency have
      historically been managed with rest, compression, and elevation. Often,
      conservative options give inadequate symptom relief and active individuals are
      rarely compliant. We report the presentation, workup, and treatment with
      fasciectomy for lower leg CCS secondary to venous hypertension. Fasciotomy and
      fasciectomy have been used for atypical claudication secondary to classic overuse
      CCS with symptom relief for many individuals. This case illustrates the
      recognition of claudication induced by CCS secondary to venous insufficiency and
      an approach to treatment with fasciectomy with a promising outcome. 

PMID- 24911799
TI  - Endovascular repair with the chimney technique for stanford type B aortic
      dissection involving right-sided arch with aberrant left subclavian artery.
AB  - A 68-year-old man, having right-sided aortic arch (RAA), underwent thoracic
      endovascular aortic repair (TEVAR) to treat Stanford B type dissection with the
      chimney technique to extend the proximal landing zone between his right
      subclavian artery and left subclavian artery (LSA). Six-month follow-up showed
      that there was sufficient cerebral infusion and positive aortic remodeling, and
      the chimney stents were patent. The results show the safety and effectiveness of
      chimney TEVAR for Stanford type B dissection in patients having RAA with an
      aberrant LSA who have no sufficient proximal fixation zone. 

PMID- 24911800
TI  - Neural damage biomarkers during open carotid surgery versus endovascular
      approach.
AB  - BACKGROUND: Carotid endarterectomy (CEA) is the gold standard for treating severe
      carotid artery stenosis, whereas carotid artery stenting (CAS) represents an
      endovascular alternative. The objective of this study was to assess the potential
      neural damage following open or endovascular carotid surgery measured by
      peripheral blood concentration of 3 biomarkers: S100beta, matrix
      metalloproteinase-9 (MMP-9), and d-dimer. METHODS: Data for this prospective
      investigation were obtained from the Carotid Markers study (January 2010-2011),
      which sought to measure the levels of specific biomarkers of neuronal damage and
      thrombosis on candidates to CEA or CAS presenting at the Department of Vascular
      Surgery of the Nuovo Ospedale S. Agostino Estense of Modena (Italy) at baseline
      and at 24 hr after surgery. Relevant medical comorbidities were noted. RESULTS: A
      total of 113 consecutive patients were enrolled in the study, 41 in the
      endarterectomy group and 72 in the endovascular group. The baseline levels of the
      studied biomarkers did not show any statistically significant difference between
      the groups with the exception of MMP-9, which showed higher concentrations in the
      endovascular group (median 731 vs. 401, P = 0.0007), while 24 hr after surgery
      the endarterectomy group featured significantly higher peripheral blood
      concentrations of MMP-9, S100beta, and d-dimer. Conversely, no significant
      difference was detected in the endovascular group except the d-dimer level.
      CONCLUSIONS: Neural damage biomarkers demonstrated a substantial difference
      between open and endovascular carotid surgery, which, if performed in selected
      patients, may become a less invasive alternative to CEA.

PMID- 24911801
TI  - Catheter-directed thrombolytic intervention is effective for patients with
      massive and submassive pulmonary embolism.
AB  - BACKGROUND: Massive pulmonary embolism (MPE) is a significant cause of mortality
      and, with submassive pulmonary embolism (SPE), is associated with chronic
      thromboembolic pulmonary hypertension, resulting in ongoing patient morbidity.
      Standard treatment is anticoagulation, although systemic thrombolytic therapy has
      been shown to reduce early mortality in patients with MPE and improve
      cardiopulmonary hemodynamics in patients with SPE. However, systemic lysis is
      associated with significant bleeding risk. Early reports of catheter-directed
      techniques (CDT) suggest favorable outcomes in patients with MPE and SPE with
      reduced risk of hemorrhage. The purpose of this study is to evaluate efficacy and
      safety outcomes in MPE and SPE patients treated with CDT. METHODS: Seventeen
      patients treated with CDT for MPE and SPE were clinically and hemodynamically
      evaluated. Patients were grouped by severity of pulmonary embolism: MPE (n = 5)
      or SPE (n = 12). Pre- and post-interventional measures were assessed, including
      pulmonary artery pressures (PAPs), cardiac biomarkers, tricuspid regurgitation,
      right ventricular (RV) dilatation, and systolic function. Nine patients had
      contraindications to systemic thrombolytic therapy. RESULTS: PAP was elevated in
      94% at presentation. The average dose of recombinant tissue plasminogen activator
      (rt-PA) was 31 mg; 44 mg in MPE and 26 mg in SPE. Pre- and post-intervention PAPs
      were recorded in 13 patients. All demonstrated an acute reduction in
      posttreatment PAP, averaging 37%. At presentation, all MPE and 10 (83%) SPE
      patients showed both RV dilatation and reduced function on echocardiography,
      which normalized in 76% (13/17) and improved in 24% (4/17) after CDT. Patients
      who demonstrated left ventricle underfilling before CDT (2 [40%] MPE and 2 [20%]
      SPE) normalized after CDT. All MPE and 11 (92%) SPE patients had tricuspid
      regurgitation on echocardiography pretreatment, which resolved in 60% and 58% of
      MPE and SPE patients, respectively. One delayed mortality occurred in an MPE
      patient who was hypotensive and hypoxic at presentation. There was one puncture
      site bleed. CONCLUSIONS: CDT was successful in the acute management of patients
      with MPE and SPE. CDT rapidly restores cardiopulmonary hemodynamics using reduced
      doses of rt-PA. These observations suggest that CDT should be considered in MPE
      and SPE patients to rapidly restore cardiopulmonary hemodynamics, reduce acute
      morbidity and mortality, reduce bleeding complications, and potentially avoid
      long-term morbidity.

PMID- 24911802
TI  - Recanalization rates after acute deep vein thrombosis: a single-center experience
      using a newly proposed vein diameter variation index.
AB  - BACKGROUND: Duplex ultrasound scanning (DUS) is the method of choice for
      diagnosis of deep vein thrombosis (DVT). However, only a few studies have
      performed prospective serial DUS after an acute episode of DVT to assess its
      evolution. This study aimed to report our experience using DUS combined with a
      thrombosis score (TS) and a newly proposed vein diameter variation index (VDVI)
      to evaluate the rate of resolution of DVT by assessing and quantifying the early
      stages of vein recanalization in proximal vein segments within 6 months after an
      episode of acute lower extremity DVT. METHODS: Twelve patients with first episode
      of acute lower extremity DVT confirmed by DUS as occurring in <=10 days after the
      onset of venous thrombosis symptoms were followed up prospectively for 6 months.
      TS and VDVI were calculated at 1, 3, and 6 months to assess vein recanalization.
      Intra-thrombus arteriovenous fistula formation was also investigated and related
      to the recanalization process. RESULTS: Seven (58%) women were included, with a
      total cohort median age of 53.5 +/- 19 years. The left lower extremity was
      affected in 7 (58%) patients. DVT was diagnosed in 55 proximal vein segments. All
      patients had proximal DVT, with involvement of the external iliac, femoral, and
      popliteal veins. After 6 months, there was a significant decrease in TS and
      increase in VDVI (P < 0.001) in all proximal vein segments assessed, indicating
      thrombus regression. The more distal the DVT was, the faster was the VDVI
      increase, with most popliteal veins being recanalized at 3 months (P < 0.001).
      Intra-thrombus arteriovenous fistula was identified in 50% of patients at 1 month
      while on anticoagulation. CONCLUSIONS: The combined use of two different DUS
      based assessment tools, TS and the proposed VDVI, provided an effective method to
      prospectively assess vein recanalization rates after an episode of acute lower
      extremity DVT in this series of patients and may allow a correct evaluation of
      DVT and its resolution or progression.

PMID- 24911803
TI  - The incidence and outcome of endothermal heat-induced thrombosis after endovenous
      laser ablation.
AB  - BACKGROUND: Endovenous laser ablation (EVLA) of the saphenous vein has become one
      of the preferred treatments for treating saphenous vein reflux that has resulted
      in symptomatic lower extremity venous insufficiency or varicose veins. This
      procedure was noted during initial reports to have a low incidence of
      postoperative thrombosis of the femoral or popliteal vein adjacent to the treated
      great saphenous vein (GSV) or small saphenous vein (SSV). Later clinical
      experience suggested that the actual incidence of this event is higher and it was
      subsequently termed endothermal heat-induced thrombosis (EHIT). METHODS: We
      reviewed the office records and the pre- and post-treatment ultrasounds of
      patients undergoing EVLA in our office from 2005 to 2010 to determine the
      frequency of EHIT in patients we had treated and then graded them according to a
      previously published classification. RESULTS: There were 528 veins treated in 192
      men and 336 women. The clinical, etiology, anatomy, pathophysiology (CEAP) class
      for these patients was 1 (0), 2 (291), 3 (65), 4 (104), 5 (26), and 6 (40),
      respectively. The GSV was treated in 496 patients, the SSV in 22, and both were
      treated in 10 patients. EHIT occurred in 29 of the legs treated for an incidence
      of 5.1%. The EHIT in the femoral vein were of level 3 (3), 4 (7), 5 (12), and 6
      (3), respectively. Two patients developed EHIT in the popliteal vein after EVLA
      of the SSV. Treatment for the EHIT consisted of observation (13), anticoagulation
      (9), antiplatelet therapy (2), and nonsteroidal anti-inflammatory agents (1).
      Duration of therapy was usually 1 week, but 7 patients were treated for periods
      ranging from 1 to 7 weeks. No pulmonary emboli occurred in any of these patients.
      The EHIT resolved completely in all patients. CONCLUSIONS: EHIT after EVLA occurs
      frequently and mainly consists of low-risk level 3, 4, and 5 deep vein
      thrombosis. The risk of pulmonary embolism is low and the EHIT typically resolves
      after 1 week. It can be treated with a short course of antiplatelet or
      anticoagulation therapy, although observation appears to be sufficient as well
      for lesser grades of EHIT.

PMID- 24911804
TI  - Carotid artery stenting using a transapical approach for the treatment of
      radiation-induced carotid stenosis.
AB  - Radiation-induced stenosis of the carotid artery is considered a challenging
      entity for direct revascularization. We performed a carotid artery stenting for a
      radiation-induced stenosis using a transapical approach on an asymptomatic 63
      year-old male patient. Transapical approach, which is often used for cardiac
      surgery, was not yet described for the endovascular treatment of carotid
      stenosis. The transapical approach could be an attractive alternative path for
      patients presenting significant supra-aortic trunks lesions and unfit for direct
      approach or peripheral access. This case reports the feasibility and the safety
      of carotid artery stenting using the transapical approach in well-trained teams. 

PMID- 24911805
TI  - Endovascular management of type Ib endoleak complicating a juxtarenal aortic
      aneurysm previously treated with a multilayer stent.
AB  - BACKGROUND: To report the use of an endograft to manage a type Ib endoleak in a
      patient with a juxtarenal aortic aneurysm previously treated with a multilayer
      stent. METHODS: Under compassionate use, a 68-year-old patient with a juxtarenal
      aortic aneurysm and multiple comorbidities was treated with a multilayer flow
      modulating stent. Twelve months later a new computed tomography (CT) scan
      identified a type Ib endoleak with an increase in the aortic aneurysm size
      because of the extension of the aneurysmal disease to the aortic carrefour. A new
      endovascular procedure was then performed, deploying an aorto-biiliac
      endoprosthesis. After 18 months, serial echocolor duplex and CT scans have shown
      normal visceral arteries patency, no signs of endoleak, and sac shrinkage of 5
      mm. DISCUSSION AND CONCLUSION: In this case, the Multilayer Aneurysm Repair
      System failed to treat the abdominal aortic aneurysm and required a reoperation
      with conventional-covered stent graft for distal sealing, which may be considered
      a feasible solution to manage potential endoleaks.

PMID- 24911806
TI  - Delayed presentation and management of a common carotid pseudoaneurysm following
      penetrating trauma with a retrograde open carotid stent graft.
AB  - Traumatic injuries of the head and neck present a difficult diagnostic and
      therapeutic challenge when identified in a delayed manner. Pseudoaneurysm
      formation has been reported in the literature typically with regard to blunt
      mechanisms; however, a delayed presentation following penetrating injury is a
      rare finding, much less described. In this case report, we describe a
      pseudoaneurysm of the common carotid artery as a result of penetrating trauma to
      the thorax. 

PMID- 24911807
TI  - An approach to EVAR simulation using patient specific modeling.
AB  - BACKGROUND: The Simbionix Angiomentor Procedure Rehearsal Studio (PRS) offers
      accurate virtual anatomy for measurement, stent graft selection, and deployment
      of endovascular aneurysm repair (EVAR) devices. METHODS: Selected Gore Excluder
      EVAR cases from our EVAR database were reviewed and DICOM data loaded into the
      Simbionix Angiomentor simulator using PRS software. Using centerline measurements
      created on PRS, neck diameter (D1), length from lowest renal artery to each iliac
      bifurcation (Ll and Lr), and common iliac artery diameter (Dl and Dr) were
      recorded. All measurements for device selection were made based on data recorded
      on the simulator. Simulated EVAR was then performed using PRS on a dual limb
      endovascular simulator. Changes in device selection based on intraoperative
      measurements and use of three-dimensional (3D) anatomic overlay made by the
      attending vascular surgeon performing the case were recorded. The devices
      actually used for successful repair were considered gold standard for comparison.
      At the completion of each virtual case, simulations were rated by an experienced
      vascular surgeon for realism, imaging quality, and final product on a 5-point
      scale. RESULTS: Ten cases with complete operative data and available computed
      tomography scans were chosen at random. Fifty percent of the cases (5/10) had
      changes in device length when using the "in vivo" 3D volume filled model and
      angiographic measurements. Analysis of variance revealed no significant
      differences between the groups in any measurement-main body diameter P = 0.960;
      main body length P = 0.643; and contralateral limb length P = 0.333. Review of
      simulation scoring showed ratings of diminished realism (average 2.3/5) due to
      unrealistic ease of wire passage and gate cannulation; however, simulation
      imaging and final product were scored favorably (3.7 and 3.4, respectively).
      CONCLUSIONS: The use of centerlines, angiographic measurements, and 3D modeling
      within the PRS software approaches real-life device selection and represents an
      opportunity for high fidelity patient-specific preoperative EVAR case rehearsal.

PMID- 24911808
TI  - Do rigid dressings reduce the time from amputation to prosthetic fitting? A
      systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate whether application of a rigid dressing (RD) to the
      residual limb soon after transtibial amputation reduces the time from amputation
      to the first prosthetic casting/fitting compared with the residual limb managed
      with a soft dressing (SD). DATA SOURCES: Studies in humans were identified by a
      systematic search of MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of
      Controlled Trials to December 2013. Search terms were based on appropriate
      medical subject headings and other free-text headings combining the following key
      words: "amputation," "amputation stumps," "transtibial," "lower limb," "post
      operative dressing," "removable rigid dressing," "rigid dressing," "wound
      healing," "rehabilitation," and "prosthetic." Reference lists of the relevant
      retrieved studies were checked for further studies. Papers could be published in
      English or other languages. STUDY SELECTION: Randomized controlled trials (RCT)
      and cross-sectional studies that included adults who had an amputation of the
      lower limb were included. Initial literature search identified 356 potentially
      relevant articles. Review of abstracts and subsequently full text identified 6
      studies included in the meta-analysis. Of these studies, 2 were RCT and 4 were
      retrospective cross-sectional studies. DATA EXTRACTION: Data were extracted by
      one reviewer and then checked by another reviewer. DATA SYNTHESIS: The use of RD
      resulted in significantly shorter time from amputation to casting or fitting of
      the prosthesis. Pooled standardized mean difference (SMD) from meta-analysis
      using DerSimonian and Laird random effect model was 0.46 (95% confidence
      interval: 0.19-0.73; P = 0.001), with 54% variation in SMD attributable to
      heterogeneity (I(2) = 0.539, P = 0.06). No evidence of small study effect has
      been found. The quality of reporting of the results varied, with some important
      elements omitted in the publications. CONCLUSIONS: Patients who are fitted with
      RD post transtibial amputation commence prosthetic management sooner than those
      managed with SD.

PMID- 24911809
TI  - Suprainguinal vascular pythiosis: effective long-term outcome of aggressive
      surgical eradication.
AB  - Vascular pythiosis, a vascular infectious disease in hemoglobinopathy patients,
      caused by Pythium insidiosum, has an endemic area in tropical and subtropical
      countries. According to literature review, suprainguinal vascular pythiosis leads
      to 100% of mortality. The authors report a 35-year-old thalassemic patient who
      presented with a right inflammatory pulsatile groin mass and right limb ischemia.
      The computerized tomography angiography indicated a false aneurysm at the right
      external iliac artery and thrombosed entire right leg arteries. The management
      comprised antifungal agent, immunotherapy, and surgical removal of all infected
      arteries (high up to the right common iliac artery and above-knee amputation).
      The patient was found in a good condition at 36 months after the follow-up
      period. 

PMID- 24911810
TI  - Reentry device aided endovascular aneurysm repair in patients with abdominal
      aortic aneurysm and unilateral iliac artery occlusion.
AB  - BACKGROUND: We report 2 cases of patients undergoing endovascular aneurysm repair
      (EVAR) using reentry devices to recanalize unilateral iliac artery occlusions and
      complete a bifurcated endovascular repair. METHODS: Patient 1 is a 70-year-old
      male with an enlarging 6.5-cm abdominal aortic aneurysm (AAA) and disabling left
      leg claudication with L external iliac occlusion with patent common and internal
      iliac arteries. Patient 2 is a 67-year-old male with an asymptomatic 4.0-cm AAA
      and L iliac chronic total occlusion (CTO) and disabling claudication. Both
      patients were poor operative candidates for open repair. RESULTS: Both patients
      underwent elective percutaneous EVAR along with left iliac artery
      revascularization. Initial angiography in both cases showed a blind ending of the
      left common iliac artery. Retrograde subintimal dissection through the occluded
      iliac segment was attempted but in both cases the wire was unable to traverse
      back into the true aortic lumen. Using either the Outback LTD or Pioneer reentry
      catheter, direct visualization of the true aortic lumen was obtained to re-enter
      the true lumen. The subintimal iliac tract was then predilated to facilitate
      routine EVAR in both cases. Both patients were discharged the following day and 1
      year and 6-month follow-up imaging revealed aneurysm exclusion, no endoleak, and
      patent bilateral common iliac arteries with resolution of claudication symptoms
      and normal ankle-brachial indexes. The previously patent internal iliac artery
      was preserved. CONCLUSIONS: While not always technically possible, reentry device
      aided EVAR is safe, feasible, and durable in the mid-term and avoids the
      morbidity and mortality related to aortouniiliac/femoral-femoral bypass and open
      repair. This technique should be considered in patients with iliac artery CTO and
      concurrent AAA to allow total endovascular repair.

PMID- 24911811
TI  - Laparoscopy versus EVAR for the treatment of abdominal aortic aneurysms in the
      octogenarian.
AB  - BACKGROUND: Octogenarians are considered at high surgical risk for the treatment
      of abdominal aortic aneurysms (AAA). The laparoscopic aortic surgery (LAS) and
      the endovascular treatment (EVAR) are 2 minimum invasive techniques whose
      objective is to limit the operative traumatism. The objective of this study was
      to compare our results with short- and medium-term results with these 2
      techniques in the octogenarians. METHODS: Between January 2002 and December 2012,
      the data of 674 operated consecutive AAA (315 LAS, 172 EVAR, and 187 open
      surgeries) were collected prospectively. Eighty-seven patients aged >=80 years
      presenting a favorable anatomy were treated by LAS or EVAR. Twenty-five patients
      aged >=85 years with a favorable anatomy were excluded because we generally did
      not propose LAS to them. Statistical analysis compared the demographic data and
      the results of the 2 groups. The principal criterion of judgment (PCJ) was the
      combined rate of mortality and severe systemic complications (MSSC) at 30 days.
      An uni/multivariate model was used to determine the factors associated with the
      occurrence of the PCJ. The data were expressed as means and standard deviations.
      A P value <=0.05 was considered significant. RESULTS: Sixty-two patients (90%
      men, age 81.8 +/- 1.4 years) were included. There were 31 EVAR and 31 LAS. The 2
      groups were comparable concerning the demographic data, the comorbidities, and
      the aneurysmal anatomies. There was a nonsignificant tendency to higher rates of
      mortality (9.7 vs. 3.2%, P = 0.3) and MSSC at 30 days (16.1 vs. 3.2%, P = 0.09)
      in the LAS group. During the operation, LAS was associated with a longer
      operative time (289 +/- 85 vs. 152 +/- 57 min, P < 0.0001), more blood losses
      (1,073 +/- 763 vs. 148 +/- 194 mL, P < 0.0001), and more transfusions (2.0 +/-
      3.0 vs. 0.9 +/- 1.1 units, P = 0.048). In the postoperative period, the patients
      operated by LAS had longer reanimation and hospitalization stays (12.9 +/- 13.1
      vs. 7.0 +/- 2.5 days, P = 0.02; and 3.3 +/- 4.4 vs. 0.6 +/- 0.7 days, P = 0.002;
      respectively). However, in multivariate analysis, an operative duration >300 min
      was the only variable associated with the PCJ (P = 0.05). With a follow-up of 9.0
      +/- 10.7 month, there were 2 reinterventions in the EVAR group, whereas with a
      follow-up of 38.0 +/- 23.9 month, no reintervention was observed in the LAS
      group. CONCLUSIONS: In the short run, EVAR significantly reduces the operative
      traumatism in comparison with LAS in the octogenarian presenting an AAA with a
      favorable anatomy. However, the choice of the technique is not independently
      predictive of MSSC at 30 days. When a durable repair is desirable, LAS remains a
      possible option in the octogenarian with a good general condition presenting a
      favorable aneurysmal anatomy.

PMID- 24911812
TI  - Improving outcomes for diabetic patients undergoing revascularization for
      critical limb ischemia: does the quality of outpatient diabetic care matter?
AB  - BACKGROUND: Diabetic patients who undergo lower extremity surgical
      revascularization for critical limb ischemia (CLI) are at high risk for
      amputation or death, even when their inpatient procedures are successful. We
      hypothesized that postoperative outcomes might be improved in regions where
      diabetics with CLI receive more frequent high-quality outpatient care. METHODS: A
      retrospective cohort study was performed among 172,134 patients with CLI (52%
      male, 15% black, mean age 76 years) who underwent open and endovascular lower
      extremity revascularization procedures using Medicare claims (2004-2007), which
      included 84,653 (49%) beneficiaries who were diabetic. Regional utilization of
      annual serum cholesterol and hemoglobin A1c testing were used to assess the
      quality of outpatient diabetic care. We examined relationships between frequency
      of diabetic testing with amputation-free survival (AFS), major adverse limb
      events (MALE), and rates of readmission across all US hospital referral regions.
      RESULTS: There was significant regional variation in annual serum cholesterol and
      hemoglobin A1c testing across the United States (87% highest quartile vs. 59%
      lowest quartile, P < 0.01). Compared with the lowest quartile of diabetic
      testing, diabetic patients undergoing lower extremity revascularization in
      regions with the highest quartile of diabetic testing had significantly improved
      AFS (hazards ratio [HR]: 0.94, 95% confidence interval [CI]: 0.90-0.97; P < 0.01)
      and MALE (HR: 0.92, 95% CI: 0.89-0.96; P < 0.01) persisting up to 2 years after
      lower extremity revascularization, even after adjusting for procedure type,
      gender, age, race, and comorbidities. Moreover, the risk of 30-day readmission
      was significantly reduced in regions with the highest versus lowest quartile of
      diabetic testing (odds ratio: 0.91, 95% CI: 0.85-0.97; P < 0.01). Nondiabetic
      patients with CLI, in comparison, did not benefit to the same extent from
      undergoing revascularization in regions with high-quality outpatient diabetic
      care. CONCLUSIONS: Diabetic patients undergoing lower extremity revascularization
      in regions with higher utilization of diabetic care quality measures have
      significantly better long-term limb salvage and readmission outcomes. Our study
      underscores the importance of providing optimal outpatient care to diabetics
      following vascular surgery and outlines a potential strategy for quality
      improvement in these high-risk patients.

PMID- 24911813
TI  - Variables associated to quality of life among nursing home patients with
      dementia.
AB  - OBJECTIVE: To study which variables are associated with quality of life (QOL) in
      persons with dementia (PWD) living in nursing homes (NHs). METHODS: A cross
      sectional study included 661 PWD living in NH. To measure QOL the quality of life
      in late-stage dementia scale (QUALID) was applied. Other scales were: the
      clinical dementia rating scale (CDR), physical self-maintenance scale (PSMS), and
      neuropsychiatric inventory questionnaire (NPI-Q). RESULTS: The patients' mean age
      was: 86.9 (SD 7.7), 472 (71.4%) were women. Of all, 22.5% had CDR 1, 33.6% had
      CDR 2, and 43.9% had CDR 3. The mean PSMS score was 18.2 (SD 5.0), 43.1% lived in
      special care units, 56.9% in regular units. In a linear regression analysis NPI
      affective score (beta = 0.360, p-value < 0.001), NPI-agitation score (beta =
      0.268, p-value < 0.001), PSMS total score (beta = 0.181, p-value < 0.001), NPI
      apathy (beta = 0.144, p-value < 0.001), NPI psychosis (beta = 0.085, p-value
      0.009), CDR sum of boxes score (beta = 0.081, p-value 0.026) were significantly
      associated with QUALID total score (explained variance 44.5%). CONCLUSION:
      Neuropsychiatric symptoms, apathy, severity of dementia, and impairment in
      activities in daily living are associated with reduced QOL in NH patients with
      dementia.

PMID- 24911815
TI  - National Association of Clinical Nurse Specialists news: President's message.

PMID- 24911816
TI  - The future of complex care.

PMID- 24911814
TI  - Effect of tonic pain on motor acquisition and retention while learning to reach
      in a force field.
AB  - Most patients receiving intensive rehabilitation to improve their upper limb
      function experience pain. Despite this, the impact of pain on the ability to
      learn a specific motor task is still unknown. The aim of this study was to
      determine whether the presence of experimental tonic pain interferes with the
      acquisition and retention stages of motor learning associated with training in a
      reaching task. Twenty-nine healthy subjects were randomized to either a Control
      or Pain Group (receiving topical capsaicin cream on the upper arm during training
      on Day 1). On two consecutive days, subjects made ballistic movements towards two
      targets (NEAR/FAR) using a robotized exoskeleton. On Day 1, the task was
      performed without (baseline) and with a force field (adaptation). The adaptation
      task was repeated on Day 2. Task performance was assessed using index distance
      from the target at the end of the reaching movement. Motor planning was assessed
      using initial angle of deviation of index trajectory from a straight line to the
      target. Results show that tonic pain did not affect baseline reaching. Both
      groups improved task performance across time (p<0.001), but the Pain group showed
      a larger final error (under-compensation) than the Control group for the FAR
      target (p = 0.030) during both acquisition and retention. Moreover, a Group x
      Time interaction (p = 0.028) was observed on initial angle of deviation,
      suggesting that subjects with Pain made larger adjustments in the feedforward
      component of the movement over time. Interestingly, behaviour of the Pain group
      was very stable from the end of Day 1 (with pain) to the beginning of Day 2 (pain
      free), indicating that the differences observed could not solely be explained by
      the impact of pain on immediate performance. This suggests that if people learn
      to move differently in the presence of pain, they might maintain this altered
      strategy over time. 

PMID- 24911817
TI  - Performance improvement methods to optimize clinical workflow: a practical
      approach.

PMID- 24911818
TI  - Ethics at the end of life: an Australian perspective.

PMID- 24911819
TI  - Teaching research: strategies for a successful learning equation.

PMID- 24911820
TI  - Behavioral therapies versus other psychological therapies for depression.

PMID- 24911821
TI  - Aligning shared responsibilities with shared rewards to create an effective work
      culture.

PMID- 24911822
TI  - Integrative review of implementation strategies for translation of research-based
      evidence by nurses.
AB  - OBJECTIVES: The purpose of this review was to synthesize and critique
      experimental and/or quasi-experimental research that has evaluated implementation
      strategies for translation of research-based evidence into nursing practice.
      BACKGROUND: Successfully implementing evidence-based research can improve patient
      outcomes. Identifying successful implementation strategies is imperative to move
      research-based evidence into practice. RATIONALE: As implementation science gains
      popularity, it is imperative to understand the strategies that most effectively
      translate research-based evidence into practice. DESCRIPTION: The review used the
      CINAHL and MEDLINE (Ovid) databases. Articles were included if they were
      experimental and/or quasi-experimental research designs, were written in English,
      and measured nursing compliance to translation of research-based evidence. An
      independent review was performed to select and critique the included articles.
      OUTCOME: A wide array of interventions were completed, including visual cues,
      audit and feedback, educational meetings and materials, reminders, outreach, and
      leadership involvement. Because of the complex multimodal nature of the
      interventions and the variety of research topics, comparison across interventions
      was difficult. CONCLUSION: Many difficulties exist in determining what
      implementation strategies are most effective for translation of research-based
      evidence into practice by nurses. IMPLICATIONS: With these limited findings,
      further research is warranted to determine which implementation strategies most
      successfully translate research-based evidence into practice.

PMID- 24911823
TI  - Clinical nurse specialist as change agent: delirium prevention and assessment
      project.
AB  - PURPOSE/OBJECTIVES: The objective of this article is to address the role of the
      clinical nurse specialist (CNS) as a change agent in the implementation of a
      quality improvement program designed to prevent and assess delirium in ventilated
      patients at a community hospital. BACKGROUND: Delirium is both a common condition
      that is not well recognized among patients in the intensive care unit (ICU)
      setting and a challenging problem to manage. Patients remain ventilated in ICU
      settings longer, and often, physical/occupational therapy is not started until
      after the patient is extubated; thus, the risk for delirium is high. RATIONALE:
      The quality improvement program was implemented to recognize and decrease
      delirium in the critically ill patient. An understanding of the role of the CNS
      as the change agent provides a reference for other CNSs. The CNS's roles of
      communication, collaboration, and education in fulfilling the core competencies
      across the spheres of patient, nurse, and system are crucial when implementing
      lasting change. DESCRIPTION: A review of the literature supports the use of the
      ABCDE Bundle to better manage pain, sedation, and delirium. The CNS uses Kurt
      Lewin's 3-step model of change to implement the quality improvement program.
      OUTCOME: A CNS successfully implemented the ABCDE Bundle in a community hospital
      to improve the prevention and assessment of delirium in the ICU patient.
      CONCLUSION: This project demonstrates the CNS's ability to implement a program to
      aid in the prevention and assessment of delirium in critically ill patients in
      the ICU. IMPLICATIONS: The CNS's involvement as the change agent to implement the
      ABCDE Bundle is effective in the prevention and assessment of delirium in
      ventilated patients. The goal of the ABCDE Bundle is to extubate patients sooner
      and transfer them out of the ICU faster.

PMID- 24911824
TI  - Therapeutic hypothermia post-cardiac arrest: a clinical nurse specialist
      initiative in Pakistan.
AB  - PURPOSE: The purpose of this project was to assess the feasibility of an evidence
      based therapeutic hypothermia protocol in adult post-cardiac arrest (CA) patients
      in a university hospital in Pakistan. BACKGROUND: Cardiac arrest has a
      deleterious effect on neurological function, and survival is associated with
      significant morbidity. The International Liaison Committee of Cardiopulmonary
      Resuscitation and the American Heart Association recommend the use of mild
      hypothermia in post-CA victims to mitigate brain injury caused by anoxia. In
      Pakistan, the survival rate in CA victims is poor. At present, there are no
      hospitals in the country that use the evidence-based hypothermia intervention in
      adult post-CA victims. DESCRIPTION: This pilot project of therapeutic hypothermia
      in adult post-CA patients was implemented in a university hospital in Pakistan by
      a clinical nurse specialist in collaboration with the cardiopulmonary
      resuscitation committee and the nursing leadership of the hospital. Various
      clinical nurse specialist competencies and roles were used to address the 3
      spheres of influence: patient, nurses, and system, while executing an evidence
      based hypothermia protocol. Process and outcome indicators were monitored to
      evaluate the effectiveness and feasibility of hypothermia intervention in this
      setting. OUTCOME: The hypothermia protocol was successfully implemented in 3
      adult post-CA patients using cost-effective measures. All 3 patients were
      extubated within 72 hours after CA, and 2 patients were discharged home with good
      neurological outcome. CONCLUSION: Adoption of an evidence-based hypothermia
      protocol for adult CA patients is feasible in the intensive care setting of a
      university hospital in Pakistan. IMPLICATIONS: The process used in the project
      can serve as a road map to other hospitals in resource-limited countries such as
      Pakistan that are motivated to improve post-CA outcomes. This experience reveals
      that advanced practice nurses can be instrumental in translation of evidence into
      practice in a healthcare system in Pakistan.

PMID- 24911825
TI  - Clinical nurse specialists lead teams to impact glycemic control after cardiac
      surgery.
AB  - PURPOSE: The purpose of this evidence-based practice improvement project was to
      improve patients' blood glucose control after cardiac surgery, specifically
      aiming to keep blood glucose levels less than 200 mg/dL. BACKGROUND/RATIONALE:
      Glycemic control is essential for wound healing and infection prevention.
      Multiple factors including the use of corticosteroids and the stress of critical
      illness put cardiac surgery patients at greater risk for elevated blood glucose
      levels postoperatively. A Surgical Care Improvement Project measure related to
      infection prevention calls for the morning blood glucose level (closest to 6:00
      AM) to be less than 200 mg/dL on postoperative days 0 to 2. Patients on our
      cardiothoracic surgery unit were experiencing blood glucose levels greater than
      benchmark goals. DESCRIPTION: A practice improvement effort was designed to
      decrease the number of blood glucose results greater than 200 mg/dL after cardiac
      surgery. The clinical nurse specialists for diabetes and cardiac surgery worked
      with nursing staff and the interdisciplinary team to implement a 4-pronged
      approach to improve efficiency in care processes: (1) increase frequency of
      glucose monitoring, (2) improve accessibility of insulin orders, (3) develop
      delegation protocol to facilitate nurse-initiated insulin infusion, and (4)
      implement revised insulin infusion protocol. OUTCOMES: Hyperglycemia was
      identified more quickly, and a nurse-initiated protocol prompted more timely use
      of revised insulin infusion orders and involvement of the diabetes specialty
      team. Clinically significant improvement in postoperative glycemic control was
      achieved. CONCLUSIONS: Empowering nurses to initiate hyperglycemia treatment and
      consultation by diabetes specialists may greatly improve efficiency in care
      processes and clinical outcomes for cardiac surgery patients. IMPLICATIONS:
      Clinical nurse specialists are well positioned to plan and implement
      interventions that facilitate an evidence-based approach to glycemic management
      after cardiac surgery.

PMID- 24911826
TI  - Kelly Goudreau profile.

PMID- 24911827
TI  - The patient's voice--does it still matter?: The February 2014 landmark case
      Westminster London Court of Protection deciding in favor of Manuela Sykes'
      petition to return home despite suffering from dementia.

PMID- 24911828
TI  - Hyperreactive Malarious Splenomegaly and AIDS: a case report.
AB  - Malaria is endemic in the North of Brazil. However, Hyperreactive Malarious
      Splenomegaly (HMS) has been rarely described. Splenomegaly in HIV/Aids infection
      has a large differential diagnosis, but malaria is a cause of gross splenomegaly,
      regardless of the HIV status. In this paper, we report the case of a 50-year-old
      man, HIV positive, with massive splenomegaly and multiple malaria infections in
      the past. He fulfilled the criteria for HMS, received a short course of anti
      malarial treatment and weekly quimioprofilatic Chloroquine. In 9 months, he had
      great clinical and laboratorial improvement confirming the HMS, a rare diagnosis
      in Brazil. 

PMID- 24911829
TI  - In situ probing of doping- and stress-mediated phase transitions in a single
      crystalline VO2 nanobeam by spatially resolved Raman spectroscopy.
AB  - We demonstrate an experimental in situ observation of the temperature-dependent
      evolution of doping- and stress-mediated structural phase transitions in an
      individual single-crystalline VO2 nanobeam on a Au-coated substrate under
      exposure to hydrogen gas using spatially resolved Raman spectroscopy. The
      nucleation temperature of the rutile R structural phase in the VO2 nanobeam upon
      heating under hydrogen gas was lower than that under air. The spatial structural
      phase evolution behavior along the length of the VO2 nanobeam under hydrogen gas
      upon heating was much more inhomogeneous than that along the length of the same
      nanobeam under air. The triclinic T phase of the VO2 nanobeam upon heating under
      hydrogen gas transformed to the R phase and this R phase was stabilized even at
      room temperature in air after sample cooling. In particular, after the VO2
      nanobeam with the R phase was annealed at approximately 250  degrees C in air, it
      exhibited the monoclinic M1 phase (not the T phase) at room temperature during
      heating and cooling cycles. These results were attributed to the interplay
      between hydrogen doping and stress associated with nanobeam-substrate
      interactions. Our study has important implications for engineering metal
      insulator transition properties and developing functional devices based on VO2
      nanostructures through doping and stress.

PMID- 24911830
TI  - Multifunctional DNA-gold nanoparticles for targeted doxorubicin delivery.
AB  - In this report we describe the synthesis, characterization, and cytotoxic
      properties of DNA-capped gold nanoparticles having attached folic acid (FA), a
      thermoresponsive polymer (p), and/or poly(ethylene glycol) (PEG) oligomers that
      could be used to deliver the anticancer drug doxorubicin (DOX) in chemotherapy.
      The FA-DNA oligomer used in the construction of the delivery vehicle was
      synthesized through the reaction of the isolated folic acid N-hydroxysuccinimide
      ester with the amino-DNA and the conjugated DNA product was purified using high
      performance liquid chromatography (HPLC). This approach ultimately allowed
      control of the amount of FA attached to the surface of the delivery vehicle.
      Cytotoxicity studies using SK-N-SH neuroblastoma cells with drug loaded delivery
      vehicles were carried out using a variety of exposure times (1-48 h) and recovery
      times (1-72 h), and in order to access the effects of varying amounts of attached
      FA, in culture media deficient in FA. DOX loaded delivery vehicles having 50% of
      the DNA strands with attached FA were more cytotoxic than when all of the strands
      contained FA. Since FA stimulates cell growth, the reduced cytotoxicity of
      vehicles fully covered with FA suggests that the stimulatory effects of FA can
      more than compensate for the cytotoxic effects of the drug on the cell
      population. While attachment of hexa-ethylene glycol PEG(18) to the surface of
      the delivery vehicle had no effect on cytotoxicity, 100% FA plus the
      thermoresponsive polymer resulted in IC50 = 0.48 +/- 0.01 for an exposure time of
      24 h and a recovery time of 1 h, which is an order of magnitude more cytotoxic
      than free DOX. Confocal microscopic studies using fluorescence detection showed
      that SK-N-SH neuroblastoma cells exposed to DOX-loaded vehicles have drug
      accumulation inside the cell and, in the case of vehicles with attached FA and
      thermoresponsive polymer, the drug appears more concentrated. Since the
      biological target of DOX is DNA, the latter observation is consistent with the
      high cytotoxicity of vehicles having both FA and the thermoresponsive polymer.
      The study highlights the potential of DNA-capped gold nanoparticles as delivery
      vehicles for doxorubicin in cancer chemotherapy. 

PMID- 24911832
TI  - Population pharmacokinetics of cilengitide in adult and pediatric cancer patients
      from a nonlinear mixed-effects analysis.
AB  - Cilengitide is an alphavbeta3/alphavbeta5-integrin inhibitor investigated as an
      anticancer agent. This study aimed to develop a cilengitide population
      pharmacokinetic model using nonlinear mixed-effects modeling of 136 adult
      patients with advanced solid tumors and to scale the pharmacokinetic parameters
      to the pediatric population. A stepwise approach was used, beginning with
      exploratory analyses checking database/target covariate relationships. A two
      compartment structural model was developed to describe cilengitide's
      concentration-time profile and assess covariates' impact on pharmacokinetic
      parameters. A bootstrap procedure validated the base/final model stability. A two
      compartment model best described concentration-time data. Estimated structural
      model parameters were: 2.79 L h(-) (1)  m(-) (2) central compartment mean
      systemic clearance, 6.75 L m(-) (2) central compartment volume of distribution,
      1.3 L h(-) (1)  m(-) (2) intercompartmental clearance, and 3.85 L m(-) (2)
      peripheral compartment volume of distribution. Mean half-life was 0.9 and 3.8 h
      (alpha/beta-phase). Co-medications and study populations had no impact, as the
      different studies were not significant model covariates. Weight and body surface
      area correlated with the pharmacokinetic parameters (r = 0.95, P < 0.01).
      Pharmacokinetic parameters were consistent with individual study-derived
      parameters; their allometric scaling enabled pediatric pharmacokinetic profile
      predictions as corroborated by independent data. This model provides the basis
      for pharmacokinetic profile simulations of different dosages/regimens in
      different populations. 

PMID- 24911834
TI  - In search of real autonomy for fertility patients.
AB  - Nearly one in eight infants in the United States is born preterm. A variety of
      factors are associated with preterm birth, including multiplicity. In the United
      States fertility treatments are currently associated with high rates of
      multiplicity, but these rates could be reduced significantly if changes can be
      made to fertility treatment policy and practice. These include reducing the
      financial pressure on patients to prioritize pregnancy chances over safety by
      expanding insurance coverage and altering the way we calculate success rates and
      insurance benefits so that two consecutive single embryo transfers is equivalent
      to one double embryo transfer. 

PMID- 24911835
TI  - Facile fabrication of a three-dimensional cross-linking TiO2 nanowire network and
      its long-term cycling life for lithium storage.
AB  - We describe a simple preparation of amorphous TiO2 nanomaterial through a simple
      dealloying method with high throughput at room temperature. The as-made TiO2
      sample has a unique three-dimensional network structure built by cross-linking
      nanowires with the diameter of ~5 nm. As an anode material for Li-ion batteries,
      the TiO2 product exhibits high capacities and a long cycling life at high rates
      of 500 and 1000 mA g(-1). In addition, it has a good rate capability. The as-made
      TiO2 nanowire network shows great application potential as an anode material with
      the advantages of unique performance and easy preparation. 

PMID- 24911836
TI  - Electronic and optical properties of graphene antidot lattices: comparison of
      Dirac and tight-binding models.
AB  - The electronic properties of graphene may be changed from semimetallic to
      semiconducting by introducing perforations (antidots) in a periodic pattern. The
      properties of such graphene antidot lattices (GALs) have previously been studied
      using atomistic models, which are very time consuming for large structures. We
      present a continuum model that uses the Dirac equation (DE) to describe the
      electronic and optical properties of GALs. The advantages of the Dirac model are
      that the calculation time does not depend on the size of the structures and that
      the results are scalable. In addition, an approximation of the band gap using the
      DE is presented. The Dirac model is compared with nearest-neighbour tight-binding
      (TB) in order to assess its accuracy. Extended zigzag regions give rise to
      localized edge states, whereas armchair edges do not. We find that the Dirac
      model is in quantitative agreement with TB for GALs without edge states, but
      deviates for antidots with large zigzag regions. 

PMID- 24911837
TI  - Elevated plasma visfatin levels correlate with poor prognosis of gastric cancer
      patients.
AB  - Visfatin is a proinflammmatory cytokine with accumulating evidence for its rise
      in circulation of cancer patients. This study aimed to evaluate the relationship
      between preoperative plasma visfatin level and prognosis of gastric cancers.
      Preoperative plasma visfatin levels of 262 patients with gastric cancers and
      plasma visfatin levels of 262 healthy individuals were determined using enzyme
      linked immunosorbent assay. Preoperative plasma visfatin level was substantially
      higher in patients than in healthy subjects. Plasma visfatin levels were
      associated with invasion depth, lymph node metastasis, distant metastasis,
      peritoneal dissemination, tumor size and tumor node metastasis stage.
      Multivariate analysis revealed that high plasma visfatin level was an independent
      factor for death. Receiver operating characteristic curve analysis showed that
      plasma visfatin level predicted death with high area under curve. Multivariate
      Cox regression analysis identified plasma visfatin level as an independent
      predictor of overall survival. Thus, our results suggest that high preoperative
      plasma visfatin level is associated with prognostic factors for gastric cancer as
      well as may play a role as prognostic biomarker in gastric cancer survival. 

PMID- 24911839
TI  - Aggregation, fusion, and leakage of liposomes induced by peptides.
AB  - Biological membranes are heterogeneous systems. Their functions are closely
      related to the lipid lateral segregation in the presence of membrane proteins. In
      this work, we designed two peptides, amphiphilic cationic peptides K3L8K3 and
      nonamphiphilic peptides K20, and studied their interactions with binary liposomes
      in different phases (Lalpha, Lbeta', and Lalpha/Lbeta'). As mimics of membrane
      proteins, both K3L8K3 and K20 can cause the liposomes to aggregate, fuse, or
      leak. These processes were closely related to the phases of liposomes. For the
      liposomes in Lalpha phase, heavy aggregation, fusion, and leakage were observed
      in the presence of either K20 or K3L8K3. For the liposomes in Lbeta' phase,
      neither K3L8K3 nor K20 can induce fusion or leakage. For the liposomes in
      Lalpha/Lbeta' phase, K3L8K3 caused the liposomes to aggregate, fuse, and leak,
      while K20 only led to aggregation. The kinetics of aggregation, fusion, and
      leakage in each phase were recorded, and they were related to the lipid demixing
      in the presence of the peptide. Our work not only gained insight into the effect
      of the lipid demixing on the interactions between peptide and membrane, but also
      helped in developing drug delivery vehicles with liposomes as the platform. 

PMID- 24911838
TI  - Functional conservation of coenzyme Q biosynthetic genes among yeasts, plants,
      and humans.
AB  - Coenzyme Q (CoQ) is an essential factor for aerobic growth and oxidative
      phosphorylation in the electron transport system. The biosynthetic pathway for
      CoQ has been proposed mainly from biochemical and genetic analyses of Escherichia
      coli and Saccharomyces cerevisiae; however, the biosynthetic pathway in higher
      eukaryotes has been explored in only a limited number of studies. We previously
      reported the roles of several genes involved in CoQ synthesis in the fission
      yeast Schizosaccharomyces pombe. Here, we expand these findings by identifying
      ten genes (dps1, dlp1, ppt1, and coq3-9) that are required for CoQ synthesis.
      CoQ10-deficient S. pombe coq deletion strains were generated and characterized.
      All mutant fission yeast strains were sensitive to oxidative stress, produced a
      large amount of sulfide, required an antioxidant to grow on minimal medium, and
      did not survive at the stationary phase. To compare the biosynthetic pathway of
      CoQ in fission yeast with that in higher eukaryotes, the ability of CoQ
      biosynthetic genes from humans and plants (Arabidopsis thaliana) to functionally
      complement the S. pombe coq deletion strains was determined. With the exception
      of COQ9, expression of all other human and plant COQ genes recovered CoQ10
      production by the fission yeast coq deletion strains, although the addition of a
      mitochondrial targeting sequence was required for human COQ3 and COQ7, as well as
      A. thaliana COQ6. In summary, this study describes the functional conservation of
      CoQ biosynthetic genes between yeasts, humans, and plants. 

PMID- 24911841
TI  - Hydrocarbon toxicity: A review.
AB  - CONTEXT: Clinical effects of hydrocarbon exposure have been reported since 1897.
      These substances are ubiquitous, and their exposures are common. The specific
      hydrocarbon and route of exposure will determine the clinical effect, and an
      understanding of this is helpful in the care of the hydrocarbon-exposed patient.
      OBJECTIVE: To complete a comprehensive review of the literature on hydrocarbon
      toxicity and summarize the findings. METHODS: Relevant literature was identified
      through searches of Medline (PubMed/OVID) and Cochrane Library databases
      (inclusive of years 1975-2013), as well as from multiple toxicology textbooks.
      Bibliographies of the identified articles were also reviewed. Search terms
      included combinations of the following: hydrocarbons, inhalants, encephalopathy,
      coma, cognitive deficits, inhalant abuse, huffing, sudden sniffing death,
      toluene, renal tubular acidosis, metabolic acidosis, arrhythmia, dermatitis, and
      aspiration pneumonitis. All pertinent clinical trials, observational studies, and
      case reports relevant to hydrocarbon exposure and published in English were
      reviewed. Chronic, occupational hydrocarbon toxicity was not included. RESULTS:
      Exposure to hydrocarbons occurs through one of the following routes: inhalation,
      ingestion with or without aspiration, or dermal exposure. Inhalational abuse is
      associated with central nervous system depression, metabolic acidosis, and
      arrhythmia. The exact mechanism of the CNS depression is unknown, but
      experimental evidence suggests effects on NMDA, dopamine, and GABA receptors.
      Chronic toluene inhalation causes a non-anion gap metabolic acidosis associated
      with hypokalemia. Halogenated hydrocarbon abuse can cause a fatal malignant
      arrhythmia, termed "sudden sniffing death". Individuals who regularly abuse
      hydrocarbons are more likely to be polysubstance users, exhibit criminal or
      violent behavior, and develop memory and other cognitive deficits. Heavy, long
      term use results in cerebellar dysfunction, encephalopathy, weakness, and
      dementia. Neuroimaging may demonstrate leukoencephalopathy in these cases. Acute
      exposures improve with cessation of exposure. Electrolyte and fluid replacement
      will improve metabolic acidosis. Arrhythmias are precipitated via catecholamine
      surge, and beta blockers are presumed protective. Aspiration of hydrocarbons
      causes a potentially fatal pneumonitis. Symptoms may include cough, wheezing
      respiratory distress, and hypoxia. Bilateral interstitial infiltrates may be
      delayed for several hours after the development of pneumonitis. Treatment
      consists of supportive care, supplemental oxygen, and may require intubation and
      admission to an intensive care unit in severe cases. Unfortunately, aspiration
      pneumonitis remains a leading cause of poisoning mortality in children. Dermal
      exposure can cause dermatitis, chemical burns, and defatting injury. Oral
      exposure can cause local irritation as well as vomiting, diarrhea, and abdominal
      pain. CONCLUSION: Acute hydrocarbon exposure can result in a wide array of
      pathology, such as encephalopathy, pneumonitis, arrhythmia, acidosis, and
      dermatitis. Intentional inhalational and accidental ingestion exposures with
      aspiration lead to the greatest morbidity and mortality.

PMID- 24911840
TI  - Effect of corneal hydration on the quality of the femtosecond laser anterior
      lamellar cut.
AB  - The goal of this study was to assess the effect of corneal hydration on the
      quality of the femtosecond laser (FSL) anterior lamellar cut. The Visumax FSL was
      used to dissect an 8-mm-diameter corneal flap in 22 eye bank corneas showing
      various levels of hydration. The intended ablation depth was 220 um in all eyes,
      which corresponded to the maximal depth available with this laser. After the cut,
      the achieved ablation depth was measured using optical coherence tomography
      images, flap separability was assessed by measuring the mean force generated to
      detach the flap, and stromal bed roughness was assessed by measuring the Haralick
      contrast level on the 1000* scanning electron microscopy images of the ablated
      surfaces. The preoperative central corneal thickness ranged from 547 to 1104 um
      (mean +/- SEM: 833 +/- 30 um). A negative correlation was found between the level
      of corneal hydration and the ablation depth measured in the mid-peripheral cornea
      (r =  -0.626, p = 0.003), the ablation being more superficial in more edematous
      corneas. The Haralick contrast also tended to increase as a function of corneal
      hydration (r = 0.416, p = 0.061), suggesting that laser ablation in edematous
      corneas results in rougher stromal surfaces. These results support the hypothesis
      that the quality of the FSL lamellar cut decreases as the level of corneal
      hydration increases. Although FSL is still considered in the field as the tool of
      the future for corneal dissection, a better understanding of the limits of this
      tool will be needed before it can replace manual or automated stromal dissection
      techniques in hydrated corneas.

PMID- 24911843
TI  - Risk factors of severe atopic dermatitis in childhood: single-center experience.
AB  - The aim of this study was to evaluate the risk factors of disease severity to
      facilitate better management of children with severe atopic dermatitis (AD). All
      the patients were diagnosed using Hanifin-Rajka criteria. After medical and
      family histories were obtained and a detailed physical examination was performed,
      disease severity was determined with the objective SCORing Atopic Dermatitis
      (SCORAD) index. Skin prick tests were performed, and percent of peripheral blood
      eosinophils, total serum IgE and specific IgE were measured. The median age of
      the 501 patients was 15 months (interquartile range [IQR]: 6-40 months), and
      62.9% (315) were male. Sensitization to at least one allergen and foods was
      observed in 40.3% (202) and 30.9% (155) of all patients, respectively. Of the
      study group, 17.6% (88) had severe disease. When logistic regression analyses
      were performed, with adjustments, the risk factors for severe AD were determined
      to be eosinophilia (odds ratio [OR] 1.137, 95% confidence interval [CI] 1.062
      1.217; p=0.003) and food allergen sensitization (OR: 1.937, 95%CI: 1.217-3.084;
      p=0.005). The patients with severe AD had sensitization to common allergens, food
      allergens and eosinophilia more frequently than those with mild-moderate disease
      (p=0.001, p=0.001 and p=0.005, respectively). Eosinophilia may predict severe
      disease and allergic sensitization. Further large-scale follow-up studies are
      needed to improve the reliability and relevance of this relation. 

PMID- 24911845
TI  - Factors affecting mortality in stage 3b necrotizing enterocolitis.
AB  - This study aimed to determine the factors that may affect the development of
      mortality in patients with stage 3b necrotizing enterocolitis (NEC). Between
      January 2005 and December 2012, patients with the diagnosis of stage 3b NEC who
      were surgically treated were enrolled in the study. Gestational age, birth
      weight, presence of hypoxemia history, major congenital heart diseases, enteral
      feeding, age at perforation, drainage type, operation, and laboratory findings
      were considered regarding their possible relationship with mortality. Thirty-one
      patients were enrolled in this study. Following treatment, 15 patients died,
      while 16 patients recovered and were discharged. Feeding type, high levels of
      prothrombin time (PT), activated partial thromboplastin time (aPTT), creatinine,
      and low platelet count, as well as need of inotropic support were associated with
      mortality. When the cut-off point of platelet level for mortality development in
      stage 3b NEC was calculated by receiver operating characteristic (ROC) curve, the
      cut-off point for thrombocyte level was found to be 110,000/uL, with 93.3%
      sensitivity and 87.5% specificity. Despite the innovations in newborn intensive
      care, the mortality rate of stage 3b NEC remains very high. Breastfeeding has a
      significantly positive impact on the survival of patients with NEC.
      Thrombocytopenia is the most important risk factor of mortality in stage 3b NEC. 

PMID- 24911844
TI  - Effect of supplementary zinc on body mass index, pulmonary function and
      hospitalization in children with cystic fibrosis.
AB  - Zinc deficiency, which is common in patients with cystic fibrosis (CF), can lead
      to several complications that may increase the number of hospital admissions in
      this group of patients. As supplementary zinc can prevent such complications,
      this study was performed to evaluate the effect of supplementary zinc on body
      mass index (BMI), forced expiratory volume in one second (FEV1) and number of
      hospitalizations in CF patients. In this study, 30 children with CF, who were
      referred to the Digestive Diseases Clinic of the Children's Medical Center in
      Tehran, were enrolled. Supplementary zinc of 2 mg/kg per day was administered to
      all patients. Serum level of zinc, alkaline phosphatase, and albumin as well as
      BMI, FEV1, and number of hospitalizations were compared before and after zinc
      administration. Height (p<0.001), weight (p<0.001) and BMI (p=0.001) were
      significantly increased after zinc, while the number of hospitalizations was
      significantly decreased (p=0.023). In contrast to patients with normal pulmonary
      function tests who received supplement therapy, BMI was not increased in those
      with abnormal pulmonary function after supplementary zinc. Supplementary zinc can
      increase BMI in CF patients, mostly in those with normal pulmonary function.
      While supplementary zinc may decrease the number of hospitalizations, other
      factors can also influence the hospitalization number. 

PMID- 24911846
TI  - Secular trend of menarche age in an immigrant urban city in Turkey: Izmir.
AB  - The purpose of this study was to investigate the secular trend of menarche age
      within the last 35 years in an immigrant urban city in Turkey-Izmir. We found the
      mean age at menarche as 13.10+/-1.18 years for 121,257 women. The reported mean
      age at menarche showed a decreasing trend over time. For women born before 1963
      (>=40 years of age), the mean age at menarche was 13.08+/-1.21 years. For women
      born from 1964-1973 (30-39 years of age), the mean age at menarche was 13.12+/
      1.19 years. For women born from 1974-1983 (20-29 years of age), the mean age at
      menarche was 13.11+/-1.18 years, and for those born after 1984 (15-19 years of
      age), the mean age at menarche was 13.06+/-1.16 years (p=0.000). When divided
      according to socioeconomic status, the mean age at menarche was 13.11+/-1.11 in
      the high socioeconomic group, 13.22+/-1.25 in the middle socioeconomic group, and
      12.75+/-1.02 in the low socioeconomic group (p=0.000). In conclusion, in the
      Turkish population, the mean age at menarche has decreased from 13.12 to 13.06
      over the past 30 years, and the mean age at menarche was lower in the low
      socioeconomic group. 

PMID- 24911847
TI  - Erythema nodosum in children: evaluation of 39 patients.
AB  - Erythema nodosum (EN) has been associated with various infectious and
      noninfectious diseases. A total of 39 EN patients seen between May 2005 and
      February 2012 were evaluated retrospectively in this study. The etiology of EN
      was established in 22 of the 39 children (56.4%). Streptococcal infection was the
      most common cause (23%), followed by tularemia (10.2%) and tuberculosis (latent
      tuberculosis infection (LTBI) 5%, pulmonary tuberculosis 2.5%). Miscellaneous
      conditions were as follows: Behcet disease (2.5%), cytomegalovirus (CMV) (2.5%),
      Giardia lamblia infection (2.5%), and sarcoidosis (2.5%). Four cases had double
      diagnoses as follows: streptococcal infection plus Mycoplasma pneumoniae,
      streptococcal infection plus LTBI, streptococcal infection plus Chlamydophila
      pneumoniae, and tularemia plus LTBI. Streptococcal infections are the most common
      causative factors of EN among children in our setting. In some cases, either of
      two diagnoses may induce EN. Etiologic factors should be investigated for the
      diagnosis and specific treatment of the underlying diseases. 

PMID- 24911848
TI  - The application of nasal synchronized intermittent mandatory ventilation in
      primary apnea of prematurity.
AB  - We aimed to evaluate the efficacy of nasal synchronized intermittent mandatory
      ventilation (nSIMV) in preterm infants with primary apnea of prematurity (AOP).
      Forty-four preterm infants with AOP were divided into the nSIMV group or nasal
      continuous positive airway pressure (nCPAP) group. Clinical symptoms, signs and
      blood gas results following nSIMV or nCPAP were compared between the two groups.
      Infants receiving nSIMV had a greater reduction in apneic spells and a greater
      decrease in bradycardia than those receiving nCPAP. Compared with the nCPAP
      group, the nSIMV group had a lower incidence of respiratory support failure (9.1%
      vs. 27.3%; p<0.05), a lower incidence of hypercarbia (4.5% vs. 18.2%; p<0.05) and
      a lower incidence of gastrointestinal complications (4.5% vs. 13.6%; p<0.05).
      This study showed that nSIMV was more effective in respiratory support in preterm
      infants with AOP. 

PMID- 24911849
TI  - Celiac disease in Williams-Beuren syndrome.
AB  - Celiac disease was previously reported to be frequent among individuals with
      Williams-Beuren syndrome; however, this suggestion was not investigated further.
      The present study was conducted to estimate the prevalence of celiac disease in a
      group of Turkish individuals with Williams-Beuren syndrome (n=33, age range: 1-24
      years) by using anti-tissue transglutaminase immunoglobulin (Ig)A and IgG, anti
      endomysium IgA, and intestinal biopsy in individuals with positive serology. The
      prevalence of celiac disease in this population was compared to its prevalence
      among healthy Turkish schoolchildren. Of all participants, celiac disease was
      diagnosed in one patient. Although statistically insignificant (p=0.145), the
      prevalence of celiac disease was higher among individuals with Williams-Beuren
      syndrome (3%) than among healthy Turkish schoolchildren (0.47%). We recommend
      questioning individuals with Williams-Beuren syndrome during routine visits
      regarding celiac disease symptoms and performing serological screening when
      consistent symptoms are present. Anti-tissue transglutaminase and anti-endomysial
      antibodies may help to identify those individuals in whom intestinal biopsy is
      indicated for the diagnosis of celiac disease. 

PMID- 24911850
TI  - Results of patch testing in pediatric patients with plantar dermatitis and
      literature review.
AB  - We aimed to determine the frequency of positive patch test reactions in pediatric
      patients with plantar dermatitis. Children diagnosed as inflammatory dermatitis
      of the plantar foot were included. Demographic and clinical characteristics of
      the patients were recorded, and patch testing was done using the European
      standard series antigens. Seventeen patients (9 females, 8 males) were included
      in the study. Ages of the patients ranged from 4-13 years, and the median age was
      7.0. Seven patients had one to three positive reactions, seven had all negative
      reactions, one showed angry back syndrome, and results of two could not be
      assessed. Dermatitis of the feet is not rare in pediatric patients, and a
      significant percentage of these patients will be diagnosed as allergic contact
      dermatitis (ACD) if detailed and appropriate patch testing is done. 

PMID- 24911852
TI  - Both parents of neonatal intensive care unit patients are at risk of depression.
AB  - Postpartum depression is a serious disorder that can be seen not only in mothers
      but also in fathers; therefore, it negatively affects the whole family.
      Hospitalization in the neonatal intensive care unit (NICU) is a stress factor for
      the parents and contributes to depression. We aimed to detect the frequency of
      postpartum depression and the contributing risk factors in parents of NICU
      patients. The Edinburgh Postnatal Depression Scale was used for mothers and the
      Beck Depression Inventory was performed for fathers in the 2nd and 6th weeks
      after delivery. At the 2nd week, maternal depression frequency was found as
      38.3%, with a mean score [ms] of 10.97+/-6.93. At the 6th week, maternal
      depression frequency was 33.3% (ms: 9.57+/-5.78). Paternal depression was 11.7%
      (ms= 7.13+/-7.35) at the 2nd week and 10.0% (ms: 6.50+/-5.79) at the 6th week.
      The frequency of maternal depression remained stable, but mean maternal
      depression scores were decreased at the 6th week compared to the 2nd week
      (p=0.023). However, paternal depression scores were similar in both periods
      (p=0.428). The infants' disease severity at admission to the NICU, as shown by
      SNAPPE-II risk scores, was positively correlated with Edinburgh depression scores
      of the mothers at the postnatal 2nd week, but not at the 6th week. In conclusion,
      NICU stay of high-risk infants may cause depression in their mothers and fathers,
      even in the absence of any previous risk factor. Although at a lower rate than in
      mothers, fathers may also suffer from depression. Parental depression screening
      and whole family support during NICU hospitalization are strongly recommended. 

PMID- 24911851
TI  - Is retinopathy of prematurity decreasing?--comparison of two different periods in
      the same NICU.
AB  - Retinopathy of prematurity is a retinal vascular disorder seen frequently in very
      premature infants, and is associated with poor clinical outcomes. The aim of the
      present study was to assess the association between the incidence of retinopathy
      of prematurity and mechanical ventilation, oxygen therapy, gestational age, and
      antenatal steroids in extremely low birth weight infants as well as to
      retrospectively analyze changes in the incidence and risk factors of retinopathy
      of prematurity over two study periods. 

PMID- 24911853
TI  - The significance of molecular studies in the long-term follow-up of children with
      beckwith- wiedemann syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is a congenital disorder of imprinting caused
      by epimutations and mutations affecting two imprinted loci on chromosome 11p15.
      Its clinical features are heterogeneous, including macrosomia, macroglossia,
      hemihyperplasia, abdominal wall defects, neonatal hypoglycemia, and increased
      risk of embryonal tumors such as Wilms tumor, adrenocortical carcinoma,
      hepatoblastoma, and neuroblastoma. The molecular and clinical heterogeneity of
      BWS makes the diagnosis challenging, but essential, since different etiologies of
      BWS have different clinical prognoses - most crucially, patients with gain of
      maternal methylation at imprinting control region type 1 (ICR1) are at
      significant risk of Wilms tumor or hepatoblastoma. We present three cases of BWS
      with different symptomatology and two different molecular diagnoses. The authors
      emphasize the importance of molecular studies in the long-term follow-up of
      children with BWS, including refinement of phenotype-genotype correlation and its
      connection with optimal management and tumor surveillance. 

PMID- 24911854
TI  - Primary abdominal wall hydatid cyst: a case report.
AB  - Hydatid disease is endemic in our country. A case of a 13-year-old girl with
      primary intermuscular hydatid cyst in the abdominal wall without other organ
      involvement is presented and discussed. At laparotomy, the entire endocyst, seen
      to push the peritoneum inwards, was totally extracted from the abdominal muscle
      planes without destroying the cyst wall. The postoperative course was uneventful.
      She is currently disease-free with a follow-up of two years. Hydatid cyst should
      be considered in endemic areas in patients presenting with a soft tissue mass in
      the abdominal wall. 

PMID- 24911855
TI  - A rare cause of recurrent respiratory tract infection: isolated absence of the
      right pulmonary artery.
AB  - Unilateral absence of a pulmonary artery (UAPA) is a rare congenital anomaly
      presenting with a wide spectrum of symptoms. UAPA is usually associated with
      cardiac anomalies. Patients with isolated UAPA may be asymptomatic or may present
      with recurrent pulmonary infections. In the present study, we report UAPA in a
      four-year-old boy presenting with recurrent respiratory tract infections. 

PMID- 24911856
TI  - Enterobius granuloma: an unusual cause of omental mass in an 11-year-old girl.
AB  - Enterobius vermicularis (pinworm) is the only nematode that infects humans. It is
      one of the most common intestinal parasites. Pinworm commonly infests the
      terminal ileum and colon, and does not cause severe morbidity unless ectopic
      infection occurs. However, granulomatous lesions caused by ectopic Enterobius
      vermicularis infection may lead to unusual clinical symptoms and may be
      misinterpreted as malignant lesions. Herein, the authors present an 11-year-old
      girl with pinworm infection who presented with abdominal pain and an omental
      mass, with special emphasis on the diagnosis and treatment. 

PMID- 24911857
TI  - A rare cause of abdominal lymphadenopathy--tularemia: report of two pediatric
      cases.
AB  - Tularemia caused by Francisella tularensis occurs worldwide in the northern
      hemisphere, with great variation in geographic and temporal occurrence. It
      generally presents as an acute febrile disease with the major clinical
      presentations including the six classic forms of tularemia: ulceroglandular,
      glandular, oculoglandular, oropharyngeal, typhoidal, and pneumonic. In contrast
      to European countries, where the ulceroglandular form is more prominent, the
      oropharyngeal form is the most common presentation in Turkey. We present rare
      cases of oropharyngeal tularemia in a 16-year-old boy and nine-year-old girl. To
      the best of our knowledge, these are the firstly described abdominal
      lymphadenopathy cases from Turkey. The second case was admitted with erythema
      nodosum, and abdominal lymphadenopathy was detected during the investigation.
      Excisional lymph node biopsy revealed abdominal tularemia. It is necessary to
      consider tularemia in the differential diagnosis of abdominal lymphadenopathy in
      tularemia regions. We also conclude that oropharyngeal tularemia can cause
      lymphadenopathy in any part of the gastrointestinal tract. 

PMID- 24911858
TI  - A patient with Behcet's disease presenting with acute urinary retention.
AB  - Behcet's disease (BD) is a multisystemic inflammatory disorder of unknown
      etiology. Neurologic involvement is known to be the most devastating feature of
      BD. The frequency and types of neurologic involvement in the pediatric age group
      are not clear, and the available information is limited to case reports. Here, we
      report a BD patient who presented with urinary incontinence as the initial
      feature of spinal cord involvement. 

PMID- 24911859
TI  - Congenital mucocele of the tongue: a case report and review of the literature.
AB  - Mucoceles are benign lesions of the oral cavity that develop as a result of
      retention or extravasation of mucous material from minor salivary glands.
      Congenital mucoceles are very rare. These lesions in newborns may interfere with
      breastfeeding and may even compromise respiratory function. A patient with a
      congenital mucocele diagnosed by prenatal ultrasound screening showing a cystic
      lesion of the tongue is presented herein. The physical examination, lesion
      evolution and imaging are described, together with the surgical management,
      histopathology and two-year follow-up. Early clinical assessment, differential
      diagnosis and magnetic resonance imaging allow clinicians to diagnose and treat
      this rare congenital condition with surgery in early infancy. 

PMID- 24911860
TI  - Rare localization of an extralobar pulmonary sequestration in a child as a
      diagnostic challenge: a case report and review of the literature.
AB  - We present a child with a rare finding of an extralobar pulmonary sequestration
      localized in the upper mediastinum. Findings of the prenatal screening enabled
      early postnatal diagnostic measures that revealed a heterogeneous mass situated
      next to the thymus. Based on the localization and inconclusive computed
      tomography images, the preoperative prediagnoses included enterogenic cyst,
      thymus cyst and teratoma. Intraoperative features of the vascular supply and
      structure of the mass drew the surgeons' suspicion to extralobar pulmonary
      sequestration, which was confirmed in the histopathological examination. The
      scans were reevaluated after the surgery. Surgical management was implemented
      prior to the occurrence of any symptoms, which led to a positive general outcome.
      The presented case should raise the awareness of radiologists, pediatric surgeons
      and other consultants involved in the diagnostic process of mediastinal lesions
      in children. The rare localization and lack of visualization of a systemic
      feeding artery can divert suspicion away from extralobar pulmonary sequestration
      in the preoperative differential diagnosis. 

PMID- 24911861
TI  - Neurothekeoma in childhood: a benign tumor mimicking malignant disease.
AB  - Neurothekeoma (NT) sometimes extends to subcutaneous adipose tissue, skeletal
      muscle or epidermis, and thus may imitate some malignant situations. A 17-year
      old female patient was admitted to another medical center with a swelling at her
      waistline. Plexiform fibrous histiocytoma was diagnosed, and she was referred to
      our clinic. Total re-excision was performed. The new pathology report indicated
      features of atypical NT. A case of atypical NT, which can be misdiagnosed as a
      malignant mesenchymal tumor, is discussed in this paper. 

PMID- 24911862
TI  - A rare sublingual cyst in an infant: oral heterotopic gastrointestinal cyst.
AB  - Oral heterotopic gastrointestinal cyst is rarely seen in the oral cavity. The
      tongue and floor of the mouth are the most commonly affected sites. These cysts
      may cause feeding and respiration problems, especially in newborns and infants. A
      benign mass was considered according to the physical examination and
      ultrasonography findings. We treated the patient with simple excision. We present
      a three-month-old female infant who was referred to us with a cystic mass in the
      sublingual region. 

PMID- 24911863
TI  - Mega-dose methylprednisolone versus pulse methylprednisolone.

PMID- 24911864
TI  - ABO incompatibility: which one matters?

PMID- 24911865
TI  - Reply: To PMID 24382531.

PMID- 24911866
TI  - Differentiation of 13 positive emotions by appraisals.
AB  - This research examined how strongly appraisals can differentiate positive
      emotions and how they differentiate positive emotions. Thirteen positive emotions
      were examined, namely, amusement, awe, challenge, compassion, contentment,
      gratitude, hope, interest, joy, pride, relief, romantic love and serenity.
      Participants from Singapore and the USA recalled an experience of each emotion
      and thereafter rated their appraisals of the experience. In general, the
      appraisals accurately classified the positive emotions at rates above chance
      levels, and the appraisal-emotion relationships conformed to predictions. Also,
      the appraisals were largely judged by participants as relevant to their positive
      emotion experiences, and the appraisal-emotion relationships were largely
      consistent across the two countries. 

PMID- 24911867
TI  - Advances in the understanding of dairy and cheese flavors: symposium
      introduction.
AB  - A symposium titled "Advances in the Understanding of Dairy and Cheese Flavors"
      was held in September 2013 at the American Chemical Society's 246th National
      Meeting in Indianapolis, IN, USA. The symposium, which was sponsored by the
      Division of Agricultural and Food Chemistry, was to discuss the state of the art
      in the detection and quantitation of flavor in dairy products. The authors of two
      of the presentations have been selected to expand on their talks by submitting
      full papers about their research. 

PMID- 24911868
TI  - Metal-organic frameworks with precisely designed interior for carbon dioxide
      capture in the presence of water.
AB  - The selective capture of carbon dioxide in the presence of water is an
      outstanding challenge. Here, we show that the interior of IRMOF-74-III can be
      covalently functionalized with primary amine (IRMOF-74-III-CH2NH2) and used for
      the selective capture of CO2 in 65% relative humidity. This study encompasses the
      synthesis, structural characterization, gas adsorption, and CO2 capture
      properties of variously functionalized IRMOF-74-III compounds (IRMOF-74-III-CH3, 
      NH2, -CH2NHBoc, -CH2NMeBoc, -CH2NH2, and -CH2NHMe). Cross-polarization magic
      angle spinning (13)C NMR spectra showed that CO2 binds chemically to IRMOF-74-III
      CH2NH2 and -CH2NHMe to make carbamic species. Carbon dioxide isotherms and
      breakthrough experiments show that IRMOF-74-III-CH2NH2 is especially efficient at
      taking up CO2 (3.2 mmol of CO2 per gram at 800 Torr) and, more significantly,
      removing CO2 from wet nitrogen gas streams with breakthrough time of 610 +/- 10 s
      g(-1) and full preservation of the IRMOF structure. 

PMID- 24911869
TI  - Perioperative pain management in hip and knee replacement surgery.
AB  - Many patients who undergo hip or knee replacement surgery today experience high
      levels of postoperative pain. Data from clinical studies and analyses of hospital
      records have demonstrated that severe postoperative pain is associated with an
      increased risk for complications, slowing of the rehabilitation process, delayed
      return to normal functioning, progression to persistent pain states, prolonged
      length of hospital stay, elevated rates of readmission, and higher overall costs.
      Orthopedic surgeons may now play a more active role in reducing the severity of
      pain following surgery, decreasing both opioid use and the incidence of opioid
      related adverse events, and eliminating breakthrough pain and analgesic gaps. The
      benefits of multimodal regimens that include a combination of agents acting
      synergistically have been established unequivocally, and many analgesic and
      anesthetic agents are now available, as well as treatment options that differ
      according to route of administration. It is therefore possible to individualize
      treatment based on the type of procedure and patient need. One exciting advance
      that offers effective, safe, and efficient analgesia for many kinds of surgical
      procedures is the introduction of an extended-release local anesthetic (liposomal
      bupivacaine) for infiltration. This new option, which can be administered
      directly into the knee or hip by an orthopedic surgeon, is an example of the
      changing paradigm in perioperative analgesia, where commitment, communication,
      and coordination across all members of the clinical care team- including the
      surgeon, anesthesiologist, pharmacist, physical therapist, and nursing staff-are
      fundamental elements of an improved standard of care. An Expert Working Group on
      Anesthesia and Orthopaedics: Critical Issues in Hip and Knee Replacement
      Arthroplasty (April 13, 2013; Dallas, Texas) evaluated current approaches to
      perioperative pain management and proposed new regimens to help achieve optimal
      outcomes in these procedures. 

PMID- 24911870
TI  - Concentration-dependent dynamics of hydrogen bonding between acetonitrile and
      methanol as determined by 1D vibrational spectroscopy.
AB  - Solutions of acetonitrile (MeCN) in methanol (MeOH) at various concentrations
      have been investigated by variable temperature Raman spectroscopy. In the nu(CN)
      region of the spectrum, the variable temperature spectra at each concentration
      show two overlapping bands from hydrogen bound and free MeCN. These two species
      undergo dynamic exchange that gives rise to increasing coalescence of the two
      bands with increasing temperature. By simulation of the band shape, the rate of
      exchange was determined at each temperature. Arrhenius plots yielded values for
      the activation energy, Ea, and the natural log of the pre-exponential factor,
      ln[A/s(-1)], for the hydrogen bond formation/cleavage. Both of these dynamic
      parameters were found to depend on the relative amounts of MeCN and MeOH in the
      solutions. In particular, two different concentration regimes of dynamic hydrogen
      bonding were observed. First, at low MeCN concentration, the dynamics are largely
      independent of changes in MeCN concentration. Second, at higher MeCN
      concentration (above ~0.2 MeCN mole fraction) the dynamics are strongly dependent
      on further increases of MeCN content. Over the range of MeCN mole fractions that
      we studied (0.03-0.5), the ln[A/s(-1)] changes from 32.5 +/- 0.1 to 30.1 +/- 0.2
      and Ea changes from 3.73 +/- 0.08 to 2.7 +/- 0.1 kcal/mol. We suggest the
      observed changes in dynamics arise from changes in the local solvent
      microstructure that occur above a critical mole fraction of MeCN. 

PMID- 24911871
TI  - Cell-mediated degradation regulates human mesenchymal stem cell chondrogenesis
      and hypertrophy in MMP-sensitive hyaluronic acid hydrogels.
AB  - Photocrosslinked methacrylated hyaluronic acid (MeHA) hydrogels support
      chondrogenesis of encapsulated human mesenchymal stem cells (hMSCs). However, the
      covalent crosslinks formed via chain polymerization in these hydrogels are
      hydrolytically non-degradable and restrict cartilage matrix spatial distribution
      and cell spreading. Meanwhile, cells are known to remodel their surrounding
      extracellular matrix (ECM) by secreting catabolic enzymes, such as MMPs.
      Hydrogels that are created with bifunctional crosslinkers containing MMP
      degradable peptide sequences have been shown to influence hMSC differentiations.
      However, crosslinks formed in the MMP-degradable hydrogels of these previous
      studies are also prone to hydrolysis, thereby confounding the effect of MMP
      mediated degradation. The objective of this study is to develop a MMP-sensitive
      but hydrolytically stable hydrogel scaffold and investigate the effect of MMP
      mediated hydrogel degradation on the chondrogenesis of the encapsulated hMSCs.
      Hyaluronic acid macromers were modified with maleimide groups and crosslinked
      with MMP-cleavable peptides or control crosslinkers containing dual thiol groups.
      The chondrogenesis of the hMSCs encapsulated in the hydrolytically stable MMP
      sensitive HA hydrogels were compared with that of the MMP-insensitive HA
      hydrogels. It was found that hMSCs encapsulated in the MMP-sensitive hydrogels
      switched to a more spreaded morphology while cells in the MMP-insensitive
      hydrogels remained in round shape. Furthermore, hMSCs in the MMP-sensitive
      hydrogels expressed higher level of chondrogenic marker genes but lower level of
      hypertrophic genes compared to cells in the MMP-insensitive hydrogels. As a
      result, more cartilage specific matrix molecules but less calcification was
      observed in the MMP-degradable hydrogels than in the MMP-insensitive hydrogels.
      Findings from this study demonstrate that cell-mediated scaffold degradation
      regulates the chondrogenesis and hypertrophy of hMSCs encapsulated in HA
      hydrogels. 

PMID- 24911872
TI  - Fludarabine downregulates indoleamine 2,3-dioxygenase in tumors via a proteasome
      mediated degradation mechanism.
AB  - Indoleamine 2,3-dioxygenase (IDO) is found in multiple malignancies and exerts
      immunosuppressive effects that are central in protecting tumors from host T
      lymphocyte rejection. IDO is an enzyme involved in the catabolism of tryptophan
      resulting in inhibition of T lymphocyte function. While inhibition of IDO
      enzymatic activity results in tumor rejection, it is still unknown how we can
      directly target IDO expression within tumors using drugs. We have chosen to
      interfere with IDO expression by targeting the key-signaling event signal
      transducer and activator of transcription 1 (STAT1). We evaluated the efficacy of
      fludarabine, previously described to inhibit STAT1 phosphorylation.
      Interestingly, fludarabine was efficient in suppressing protein expression and
      consequently IDO activity in two different cell lines derived from breast cancer
      and melanoma when IDO was activated with interferon-gamma (IFN-gamma) or
      supernatants prepared from activated T lymphocytes. However, fludarabine had no
      inhibitory effect on STAT1 phosphorylation. Other IFN-gamma-responsive genes were
      only marginally inhibited by fludarabine. The level of IDO transcript was
      unaffected by this inhibitor, suggesting the involvement of post-transcriptional
      control. Strikingly, we have found that the inhibition of proteasome partially
      protected IDO from fludarabine-induced degradation, indicating that fludarabine
      induces IDO degradation through a proteasome-dependent pathway. Currently used in
      the clinic to treat some malignancies, fludarabine has the potential for use in
      the treatment of human tumors through induction of IDO degradation and
      consequently, for the promotion of T cell-mediated anti-tumor response. 

PMID- 24911873
TI  - Increased macroH2A1.1 expression correlates with poor survival of triple-negative
      breast cancer patients.
AB  - PURPOSE: Epithelial-Mesenchymal Transition (EMT) features appear to be key events
      in development and progression of breast cancer. Epigenetic modifications
      contribute to the establishment and maintenance of cancer subclasses, as well as
      to the EMT process. Whether histone variants contribute to these transformations
      is not known. We investigated the relative expression levels of histone macroH2A1
      splice variants and correlated it with breast cancer status/prognosis/types.
      METHODS: To detect differential expression of macroH2A1 variant mRNAs in breast
      cancer cells and tumor samples, we used the following databases: GEO, EMBL-EBI
      and publisher databases (may-august 2012). We extracted macroH2A1.1/macroH2A1
      mRNA ratios and performed correlation studies on intrinsic molecular subclasses
      of breast cancer and on molecular characteristics of EMT. Associations between
      molecular and survival data were determined. RESULTS: We found increased
      macroH2A1.1/macroH2A1 mRNA ratios to be associated with the claudin-low intrinsic
      subtype in breast cancer cell lines. At the molecular level this association
      translates into a positive correlation between macroH2A1 ratios and molecular
      characteristics of the EMT process. Moreover, untreated Triple Negative Breast
      Cancers presenting a high macroH2A1.1 mRNA ratio exhibit a poor outcome.
      CONCLUSION: These results provide first evidence that macroH2A1.1 could be
      exploited as an actor in the maintenance of a transient cellular state in EMT
      progress towards metastatic development of breast tumors.

PMID- 24911874
TI  - Evolution of mitochondrial power in vertebrate metazoans.
AB  - BACKGROUND: Basal metabolic rate (BMR) has a very strong body-mass (M) dependence
      in an individual animal group, and BMR per unit mass (msBMR) converges on a
      markedly narrow range even across major taxonomic groups. However, it is here a
      basic question in metazoan biology how much BMR per unit mitochondrion (mtBMR)
      changes, and then whether mtBMR can be related to the original molecular
      mechanism of action of mt-encoded membrane proteins (MMPs) playing a central role
      in cellular energy production. METHODOLOGY/PRINCIPAL FINDINGS: Analyzing
      variations of amino-acid compositions of MMPs across 13 metazoan animal groups,
      incorporating 2022 sequences, we found a strong inverse correlation between
      Ser/Thr composition (STC) and hydrophobicity (HYD). A majority of animal groups
      showed an evolutionary pathway of a gradual increase in HYD and decrease in STC,
      whereas only the deuterostome lineage revealed a rapid decrease in HYD and
      increase in STC. The strongest correlations appeared in 5 large subunits (ND4,
      ND5, ND2, CO1, and CO3) undergoing dynamic conformational changes for the proton
      pumping function. The pathway of the majority groups is well understood as
      reflecting natural selection to reduce mtBMR, since simply raising HYD in MMPs
      (surrounded by the lipid bilayer) weakens their mobility and strengthens their
      stability. On the other hand, the marked decrease in HYD of the deuterostome
      elevates mtBMR, but is accompanied with their instability heightening a turnover
      rate of mitochondria and then cells. Interestingly, cooperative networks of
      interhelical hydrogen-bonds between motifs involving Ser and Thr residues can
      enhance MMP stability. CONCLUSION/SIGNIFICANCE: This stability enhancement lowers
      turnover rates of mitochondria/cells and may prolong even longevity, and was
      indeed founded by strong positive correlations of STC with both mtBMR and
      longevity. The lowest HYD and highest STC in Aves and Mammals are congruent with
      their very high mtBMR and long longevity.

PMID- 24911875
TI  - GFP-SCFV: expression and possible applications as a tool for experimental
      investigations of atherosclerosis.
AB  - Experimental studies on atherosclerosis are crucial for investigating its
      pathophysiology, defining new therapeutic targets, and developing new drugs and
      diagnostic tools. Thus, many imaging markers have been developed and introduced
      in experimental studies. The main advantage of these new tools is that they allow
      the noninvasive diagnosis of atherosclerotic vascular disease. Here, we describe
      the cloning, expression, purification, and stabilization of a chimeric protein
      specifically designed to probe cells and tissues for the presence of LDL(-), a
      relevant marker of atherosclerosis. The DNA sequence that encodes the anti-LDL(-)
      scFv, previously obtained from a hybridoma secreting an anti-LDL(-) monoclonal
      antibody, was inserted into the bacterial vector pET-28a(+) in tandem with a DNA
      sequence encoding GFP. The recombinant protein was expressed in high yields in E.
      coli as inclusion bodies. The applicability of GFP-scFv was assessed by ELISA,
      which determined its affinity for LDL(-) and confocal microscopy, that showed
      macrophage uptake of the protein along with LDL(-). In conclusion, our data
      suggest that the anti-LDL(-) GFP-scFv chimeric protein could be useful in studies
      on atherogenesis as well as for developing diagnostic tools for atherosclerosis.

PMID- 24911876
TI  - Enteric bacterial protein AvrA promotes colonic tumorigenesis and activates
      colonic beta-catenin signaling pathway.
AB  - Salmonella infections can become chronic and increase the risk of cancer. The
      mechanisms by which specific Salmonella organisms contribute to cancer, however,
      are still unknown. Live and attenuated Salmonella are used as vectors to target
      cancer cells, but there have been no systematic studies of the oncogenic
      potential of chronic Salmonella infections in cancer models. AvrA, a pathogenic
      product of Salmonella, is inserted into host cells during infection and
      influences eukaryotic cell pathways. In the current study, we colonized mice with
      Salmonella AvrA-sufficient or AvrA-deficient Salmonella typhimirium strains and
      induced inflammation-associated colon cancer by azoxymethane/dextran sulfate
      sodium (AOM/DSS). We confirmed Salmonella persisted in the colon for up to 45
      weeks. Salmonella was identified not only in epithelial cells on the colonic
      luminal surface and base of the crypts but also in invading tumors. Tumor
      incidence in the AvrA+infected group was 100% compared with 51.4% in the AOM/DSS
      group without bacterial gavage and 56.3% in mice infected with the AvrA- strain.
      Infection with AvrA+ strain also altered tumor distribution from the distal to
      proximal colon that might reflect changes in the microbiome. AvrA-expressing
      bacteria also upregulated beta-catenin signaling as assessed by decreased beta
      catenin ubiquitination, increased nuclear beta-catenin and increased
      phosphorylated-beta-catenin (Ser552), a marker of proliferating stem-progenitor
      cells. Other beta-catenin targets increased by AvrA included Bmi1, a cancer stem
      cell marker, matrix metalloproteinase-7, and cyclin D1. In summary, AvrA
      expressing Salmonella infection activates beta-catenin signals and enhances
      colonic tumorigenesis. Our findings provide important new mechanistic insights
      into how a bacterial protein targets proliferating stem-progenitor cells and
      contributes to cancer development. Our observations also raise a note of caution
      regarding the use of mutant Salmonella organisms as vectors for anti-cancer
      therapy. Finally, these studies could suggest biomarkers (such as AvrA level in
      gut) to assess cancer risk in susceptible individuals and infection-related
      dysregulation of beta-catenin signaling in cancer. 

PMID- 24911877
TI  - Soluble aggregates in aqueous solutions of polyion-surfactant ion complex salts
      and a nonionic surfactant.
AB  - Water-soluble aggregates based on two polyion-surfactant ion "complex salts",
      consisting of hexadecyltrimethylammonium (C16TA(+)) and polyacrylate (PA(-)) with
      either 25 or 6000 repeating units, with added nonionic surfactant octaethylene
      glycol monododecyl ether (C12E8) have been investigated. A previous phase study
      has shown that added C12E5 or C12E8 can solubilize complex salts in aqueous
      systems, and that increasing the poly(ethylene oxide) chain length of the
      nonionic surfactant and/or decreasing the polyion length favors dissolution. In
      this work we report on dynamic light scattering, NMR diffusometry, small-angle X
      ray scattering, and isothermal titration calorimetry measurements performed to
      characterize the solubilized composite aggregates in dilute aqueous solution in
      terms of size and stoichiometry. It was found that mixed aggregates of
      polyacrylate, C16TA(+) ions, and C12E8, with almost constant stoichiometry,
      coexist with free micelles of C12E8 at all investigated mixing ratios. The length
      of the polyion only weakly affects the stoichiometry of the mixed aggregates
      while strongly affecting their size and water solubility. 

PMID- 24911878
TI  - Second-stage vs first-stage caesarean delivery: comparison of maternal and
      perinatal outcomes.
AB  - Abstract In this observational study, we investigated the maternal and perinatal
      complications of caesarean delivery performed in the second stage compared with
      the first stage of labour at a tertiary hospital in Istanbul. This study was
      performed from June 2008 to July 2011. Primary maternal outcomes measured
      included intraoperative surgical complications, surgery duration, need for blood
      transfusion, endometritis, requirement for hysterectomy, unintended extension and
      length of hospital stay. Neonatal outcomes included a 5 min Apgar score <= 3,
      admission to a neonatal intensive care unit, fetal injury, septicaemia and
      neonatal death. In total, 3,817 caesarean deliveries were available for analysis;
      3,519 were performed in the first stage, and 298 in the second stage. Caesarean
      deliveries performed in the second stage were associated with increased
      intraoperative complications, unintended extensions, need for blood transfusion,
      higher rates of endometritis and requirement for hysterectomy and were,
      therefore, associated with longer operation time and hospital stay. Neonatal
      complications included a significantly low Apgar score at 5 min, increased
      neonatal death, admission to the neonatal intensive care unit, septicaemia and
      fetal injury (all p < 0.05). Caesarean deliveries performed in the second stage
      of labour were associated with higher rates of maternal and neonatal
      complications, particularly in women who had undergone previous caesarean
      delivery. 

PMID- 24911879
TI  - Cd(II) based metal-organic framework behaving as a Schottky barrier diode.
AB  - A metal-organic framework (MOF) of cadmium(ii) is reported here which is the
      first example of an experimentally achieved MOF based electronic device, and in
      the present case it is a Schottky diode. 

PMID- 24911881
TI  - Investigation of composition dependent structural and optical properties of the
      Zn(1-x)Cd(x)S, coaxial Zn(0.99-x)Cd(x)Cu(0.01)S/ZnS, Zn(0.99-x)Cd(x)Mn(0.01)S
      nanorods generated by a one-step hydrothermal process.
AB  - High-quality Zn(1-x)Cd(x)S, coaxial Zn(0.99-x)Cd(x)Cu(0.01)S/ZnS and Zn(0.99
      x)Cd(x)Mn(0.01)S nanorods (NRs) were synthesized through a one-step hydrothermal
      method. The composition of the alloyed NRs was adjusted by controlling the Zn/Cd
      molar ratios. The results showed that all of the samples had a good crystallinity
      with the typical hexagonal wurtzite structure. The Zn/Cd molar ratios and Cu and
      Mn doping played an important role in affecting the final structure, morphology
      and optical properties of the alloyed NRs. The successive shift of the XRD and PL
      patterns indicated that the NRs obtained were not a mixture of ZnS and CdS, but
      the Zn(1-x)Cd(x)S solid solution. After doping Cu(2+) (1%) ions into the Zn(1
      x)Cd(x)S NRs, the samples exhibited highly crystalline coaxial Zn(0.99
      x)Cd(x)Cu(0.01)S/ZnS core-shell NRs and showed a strong green emission peak
      centered at 509.6 nm. After doping Mn(2+) (1%) ions into the Zn(1-x)Cd(x)S NRs,
      the samples exhibited a better crystal quality and showed a strong yellow-orange
      emission peak centered at 583 nm.

PMID- 24911880
TI  - Polyhydroxyanthraquinones as quorum sensing inhibitors from the guttates of
      Penicillium restrictum and their analysis by desorption electrospray ionization
      mass spectrometry.
AB  - The endophytic fungus Penicillium restrictum was isolated from the stems of a
      milk thistle (Silybum marianum) plant. In culture, the fungus produced distinct
      red guttates, which have been virtually uninvestigated, particularly from the
      standpoint of chemistry. Hence, this study examined the chemical mycology of P.
      restrictum and, in doing so, uncovered a series of both known and new
      polyhydroxyanthraquinones (1-9). These compounds were quorum sensing inhibitors
      in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), with
      IC50 values ranging from 8 to 120 MUM, suggesting antivirulence potential for the
      compounds. Moreover, the spatial and temporal distribution of the
      polyhydroxyanthraquinones was examined in situ via desorption electrospray
      ionization-mass spectrometry (DESI-MS) imaging, demonstrating the first
      application of this technique to a guttate-forming fungus and revealing both the
      concentration of secondary metabolites at the ventral surface of the fungus and
      their variance in colonies of differing ages. 

PMID- 24911882
TI  - The interplay between hyperglycemia-induced oxidative stress markers and the
      level of soluble receptor for advanced glycation end products (sRAGE) in K562
      cells.
AB  - Formation and accumulation of advanced glycation end-products (AGE) and also
      generation of reactive oxygen species (ROS), the main causative players in the
      context of diabetes, are intensified under hyperglycemic condition. The
      consequences from AGE/RAGE interaction could be attenuated by the soluble form of
      RAGE, termed sRAGE. In the current study, we studied the link between
      hyperglycemia-induced oxidative stress and the level of soluble form of RAGE in
      K562 cells. Our data revealed a positive correlation between high glucose and/or
      AGE-modified albumin treatment and oxidative stress status. Besides, a
      significant decrease in soluble RAGE level following treatments with either AGE
      modified albumin or high glucose was observed. However, pretreatment with an
      appropriate antioxidant such as Resveratrol, markedly elevated the sRAGE level.
      Hence, sRAGE therapy could be further evaluated as an effective therapeutical
      approach to attenuate some of the diabetes complications.

PMID- 24911883
TI  - A promising approach to iPSC-based cell therapy for diabetic wound treatment:
      direct lineage reprogramming.
AB  - Successful reprogramming of somatic cells into induced pluripotent stem cells
      (iPSCs) has ushered in a new era of regenerative medicine. Several studies on
      iPSCs have corroborated their immense promise and potential for use in cell
      therapy and disease modeling. However, several shortcomings need to be overcome
      before they can be used in clinical therapy. Investigation of iPSC fate and
      physiology in vivo and ultimately, the feasibility of their application in cell
      transplantation therapy, requires more in-depth studies in living subjects. One
      recently established alternative approach to reprogramming involves the direct
      conversion of a terminally differentiated somatic cell of one type into another,
      without dedifferentiating into a pluripotent state. This direct lineage
      reprogramming strategy is significantly faster, has the potential to generate an
      enriched population of a specific subtype of cells, and hence, has wide
      implications in regenerative cell therapy. Here, we review recent advances in
      iPSC technology and summarize the research on the generation of patient-specific
      induced cell types using direct lineage conversion. Specifically, we focus on the
      scope of application of this approach in autologous cell replacement therapy for
      diabetic wound treatment.

PMID- 24911884
TI  - The ACE2/Ang-(1-7)/Mas axis can inhibit hepatic insulin resistance.
AB  - Blocking the renin-angiotensin system (RAS) can reduce the risk of diabetes.
      Meanwhile, the angiotensin (Ang)-converting enzyme-2 (ACE2)/Ang-(1-7)/Mas axis
      has recently been proposed to function as a negative regulator of the RAS. In
      previous studies, we first demonstrated that ACE2 knockout (ACE2(-/)(y)) mice
      exhibit impaired glucose tolerance or diabetes. However the precise roles of ACE2
      on glucose metabolism are unknown. Here we show that the ACE2/Ang-(1-7)/Mas axis
      can ameliorate insulin resistance in the liver. Activation of the ACE2/Ang-(1
      7)/Mas axis increases glucose uptake and decreases glycogen synthesis in the
      liver accompanied by increased expression of glucose transporters, insulin
      receptor substrates and decreased expression of enzymes for glycogen synthesis.
      ACE2 knockout mice displayed elevated levels of oxidative stress and exposure to
      Ang-(1-7) reduced the stress in hepatic cells. As a consequence of anti-oxidative
      stress, activation of the ACE2/Ang-(1-7)/Mas axis led to improved hepatic insulin
      resistance through the Akt/PI3K/IRS-1/JNK insulin signaling pathway. This is the
      first time documented that the ACE2/Ang-(1-7)/Mas axis can ameliorate insulin
      resistance in the liver. As insulin resistance in the liver is considered to be
      the primary cause of the development of type 2 diabetes, this axis may serve as a
      new diabetes target.

PMID- 24911885
TI  - Allosteric mechanisms of nuclear receptors: insights from computational
      simulations.
AB  - The traditional structural view of allostery defines this key regulatory
      mechanism as the ability of one conformational event (allosteric site) to
      initiate another in a separate location (active site). In recent years
      computational simulations conducted to understand how this phenomenon occurs in
      nuclear receptors (NRs) has gained significant traction. These results have yield
      insights into allosteric changes and communication mechanisms that underpin
      ligand binding, coactivator binding site formation, post-translational
      modifications, and oncogenic mutations. Moreover, substantial efforts have been
      made in understanding the dynamic processes involved in ligand binding and
      coregulator recruitment to different NR conformations in order to predict
      cell/tissue-selective pharmacological outcomes of drugs. They also have improved
      the accuracy of in silico screening protocols so that nowadays they are becoming
      part of optimisation protocols for novel therapeutics. Here we summarise the
      important contributions that computational simulations have made towards
      understanding the structure/function relationships of NRs and how these can be
      exploited for rational drug design.

PMID- 24911886
TI  - Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: Antiretroviral therapy (ART) reduces the morbidity and mortality of
      patients infected with HIV. Standard ART includes either nevirapine or efavirenz,
      however the efficacy of these drugs is limited in patients receiving rifampin
      treatment for tuberculosis (TB). We compared the efficacy and safety of
      nevirapine- and efavirenz-based ART regimens in patients co-infected with both
      HIV and TB through a systematic review and meta-analysis. METHODS: A
      comprehensive search of the literature was carried out to identify clinical
      trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART
      regimens in HIV-associated TB. Eligible clinical studies included at least one
      primary or secondary event; the primary event was virological response and
      secondary events were TB treatment outcomes, mortality, and safety profile.
      RESULTS: This meta-analysis compared five randomized clinical trials and four
      retrospective clinical trials. Both included patients co-infected with HIV and
      TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of
      patients achieving a virological response by the end of the follow-up was higher
      in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10,
      95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50
      copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were
      found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment
      outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents,
      nevirapine-based regimens significantly increased the risk of discontinuation of
      assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009). CONCLUSIONS: Although
      efavirenz-based ART was associated with more satisfactory virological outcomes,
      nevirapine-based ART could be considered an acceptable alternative for patients
      for whom efavirenz cannot be administered.

PMID- 24911887
TI  - Rabies and rabies virus in wildlife in mainland China, 1990-2013.
AB  - The number of wildlife rabies and wildlife-associated human and livestock rabies
      cases has increased in recent years, particularly in the southeast and northeast
      regions of mainland China. To better understand wildlife rabies and its role in
      human and livestock rabies, we reviewed what is known about wildlife rabies from
      the 1990s to 2013 in mainland China. In addition, the genetic diversity and
      phylogeny of available wildlife-originated rabies viruses (RABVs) were analyzed.
      Several wildlife species carry rabies including the bat, Chinese ferret badger,
      raccoon dog, rat, fox, and wolf. RABVs have been isolated or detected in the bat,
      Chinese ferret badger, raccoon dog, Apodemus, deer, and vole. Among them, the
      bat, Chinese ferret badger, and raccoon dog may play a role in the ecology of
      lyssaviruses in mainland China. All wildlife-originated RABVs were found to
      belong to genotype 1 RABV except for a bat-originated Irkut virus isolated in
      2012. Several substitutions were found between the glycoprotein of wildlife
      originated RABVs and vaccine strains. Whether these substitutions could affect
      the efficacy of currently used vaccines against infections caused by these
      wildlife-originated RABVs needs to be investigated further. Phylogenetic analysis
      showed that RABVs in the bat, Chinese ferret badger, and raccoon dog were
      distinct from local dog-originated RABVs, and almost all collected wildlife
      originated isolates were associated with older China clades II to V, suggesting
      the possibility of wildlife reservoirs in mainland China through the ages. 

PMID- 24911888
TI  - Exchange-induced relaxation in the presence of a fictitious field.
AB  - In the present study we derive a solution for two site fast exchange-induced
      relaxation in the presence of a fictitious magnetic field as generated by
      amplitude and frequency modulated RF pulses. This solution provides a means to
      analyze data obtained from relaxation experiments with the method called RAFFn
      (Relaxation Along a Fictitious Field of rank n), in which a fictitious field is
      created in a coordinate frame undergoing multi-fold rotation about n axes (rank
      n). The RAFF2 technique is relevant to MRI relaxation methods that provide good
      contrast enhancement for tumor detection. The relaxation equations for n=2 are
      derived for the fast exchange regime using density matrix formalism. The method
      of derivation can be further extended to obtain solutions for n>2. 

PMID- 24911889
TI  - Concentration of enteric viruses from tap water using an anion exchange resin
      based method.
AB  - Detecting low concentrations of enteric viruses in water is needed for public
      health-related monitoring and control purposes. Thus, there is a need for
      sensitive, rapid and cost effective enteric viral concentration methods
      compatible with downstream molecular detection. Here, a virus concentration
      method based on adsorption of the virus to an anion exchange resin and direct
      isolation of nucleic acids is presented. Ten liter samples of tap water spiked
      with different concentrations (10-10,000 TCID50/10 L) of human adenovirus 40
      (HAdV-40), hepatitis A virus (HAV) or rotavirus (RV) were concentrated and
      detected by real time PCR or real time RT-PCR. This method improved viral
      detection compared to direct testing of spiked water samples where the DeltaCt
      was 12.1 for AdV-40 and 4.3 for HAV. Direct detection of RV in water was only
      possible for one of the three replicates tested (Ct of 37), but RV detection was
      improved using the resin method (all replicates tested positive with an average
      Ct of 30, n=3). The limit of detection of the method was 10 TCID50/10 L for HAdV
      40 and HAV, and 100 TCID50/10 L of water for RV. These results compare favorably
      with detection limits reported for more expensive and laborious methods.

PMID- 24911890
TI  - LC-MS/MS analysis of visceral and subcutaneous adipose tissue proteomes in young
      goats with focus on innate immunity and inflammation related proteins.
AB  - The endocrine role of adipose tissue and its involvement in several physiological
      and pathological processes are well recognized. Studies on human, mouse and rat
      adipose tissues have made clear that subcutaneous and visceral deposits play
      different roles, which is also reflected by different protein and gene expression
      patterns. In ruminants, fat tissues play important biological roles not only for
      animal health, but also for quality and gain in meat and milk production. Yet
      very few studies have explored the ruminant adipose tissue proteomes. The aim of
      our study was to compare subcutaneous and visceral adipose tissues of goat,
      focusing on proteins involved in immune and inflammatory response. A 2-D LC-MS/MS
      approach followed by cluster analysis shows a clear distinction between
      subcutaneous and visceral fat tissue proteomes, and qualitative RT-PCR based
      analysis of 30 potential adipokines further confirmed the individual expression
      patterns of 26 of these, including 7 whose mRNA expression was observed for the
      first time in adipose tissues. This study provides a first description of adipose
      tissue proteomes in goat, and presents observations on novel proteins related to
      metabolic and inflammatory pathways. The mass spectrometry data have been
      deposited to the ProteomeXchange Consortium with the data set identifier
      PXD000564. BIOLOGICAL SIGNIFICANCE: The proteomic analysis of different
      subcutaneous and visceral adipose tissue deposits showed tissue specific
      differences in protein expressions of well known as well as novel adipokines.
      This highlights the importance of sampling site when studying adipose tissue's
      metabolic roles. The protein expression characteristics of adipose tissues was
      evaluated by quantitative RT-PCR, and confirmed that adipose tissues play a
      central role in controlling inflammation, detoxification and coagulation
      pathways, as well as regulation of body fat mobilization in dairy animals. These
      findings are of particular interest in farm animals where health and production
      traits are important for animal welfare and for economic gains.

PMID- 24911891
TI  - Environmental gestagens activate fathead minnow (Pimephales promelas) nuclear
      progesterone and androgen receptors in vitro.
AB  - Gestagen is a collective term for endogenous and synthetic progesterone receptor
      (PR) ligands. In teleost fishes, 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP)
      and 17alpha,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S) are the predominant
      progestogens, whereas in other vertebrates the major progestogen is progesterone
      (P4). Progestins are components of human contraceptives and hormone replacement
      pharmaceuticals and, with P4, can enter the environment and alter fish and
      amphibian reproductive health. In this study, our primary objectives were to
      clone the fathead minnow (FHM) nuclear PR (nPR), to develop an in vitro assay for
      FHM nPR transactivation, and to screen eight gestagens for their ability to
      transactivate FHM nPR. We also investigated the ability of these gestagens to
      transactivate FHM androgen receptor (AR). Fish progestogens activated FHM nPR,
      with DHP being more potent than 20beta-S. The progestin drospirenone and P4
      transactivated the FHM nPR, whereas five progestins and P4 transactivated FHM AR,
      all at environmentally relevant concentrations. Progestins are designed to
      activate human PR, but older generation progestins have unwanted androgenic side
      effects in humans. In FHMs, several progestins proved to be strong agonists of
      AR. Here, we present the first mechanistic evidence that environmental gestagens
      can activate FHM nPR and AR, suggesting that gestagens may affect phenotype
      through nPR- and AR-mediated pathways. 

PMID- 24911892
TI  - Mesenchymal stem cells differentially modulate effector CD8+ T cell subsets and
      exacerbate experimental autoimmune encephalomyelitis.
AB  - Mesenchymal stem cells (MSC) have emerged as a promising candidate for
      inflammatory suppression and disease amelioration, especially of neuro
      inflammatory diseases such as multiple sclerosis (MS). Auto-reactive CD4+ and
      CD8+ T cells acquire pathogenic IFNgamma-producing- (Type I) and IL-17A-producing
      (Type 17) effector phenotypes in MS and its animal model experimental autoimmune
      encephalomyelitis (EAE). Although MSC have been extensively demonstrated to
      suppress pathogenic effector CD4+ T cells and CD4+ T cell-mediated EAE,
      surprisingly few studies have addressed their modulation of effector CD8+ T cells
      represented in MS or their impact on CD8+ T cell-mediated EAE. We find that MSC
      differentially modulate CD8+ T cell development depending on effector T cell
      subtype. MSC drive activated low-IFNgamma producers toward an enhanced high
      IFNgamma Tc1-like phenotype but strongly inhibit the production of IL-17A and
      Tc17 polarization in vitro. These observations are underscored by differential
      MSC modulation of T cell activation, proliferation, and signature transcription
      factor up-regulation. In addition, effector CD8+ T cells co-cultured with MSC
      exhibited increased production of IL-2, a molecule known to enhance IFNgamma, yet
      suppress IL-17A, production. Based on these in vitro effects on CD8+ T cells, we
      next evaluated their impact on the severity of EAE. To better evaluate CD8+ T
      cells, we immunized mice with MOG37-50 , which is a CD8-targeted epitope. Our
      results revealed a worsening of disease, consistent with their in vitro
      stimulation of Tc1 cells. These findings highlight the emerging duality of MSC in
      immune modulation and provide implications for their future use in immune-related
      diseases.

PMID- 24911893
TI  - Enhanced survival during experimental Listeria monocytogenes sepsis in neonatal
      mice prophylactically treated with Th1 and macrophage immunoregulatory cytokines
      and mediators.
AB  - BACKGROUND: Impairments in T-cell and macrophage-mediated host defense lead to
      increased infection-related morbidity and mortality in neonates, partly because
      of immaturity in T helper (Th)1 function. Listeria monocytogenes (Lm) is an
      intracellular pathogen disproportionately causing severe disease among neonates
      and the immunocompromised. Intact macrophage and Th1-mediated immune responses
      are critical for Lm clearance. We and others have previously demonstrated
      downregulation of Th1 and macrophage immunoregulatory cytokines in cord blood
      versus adult peripheral blood. We sought to determine whether therapeutic or
      prophylactic single agent or combination recombinant murine interleukin (rmIL)
      12, rmIL-18, recombinant murine macrophage-colony stimulating factor (rmM-CSF),
      recombinant murine granulocyte macrophage-colony stimulating factor (rmGM-CSF)
      and recombinant murine interferon (rmIFN)-gamma would enhance survival during
      experimental neonatal Lm sepsis. METHODS: A 90% lethal dose (LD90) of Lm was
      established in C57/BL/6 neonatal mice. rmIL-12, rmIL-18, rmM-CSF, rmGM-CSF and
      rmIFN-gamma were administered singly or sequentially, before or after LD90 Lm
      inoculation; ampicillin was administered 24 hours after inoculation. RESULTS:
      Therapeutic doses of rmIL-12, rmIL-18, rmM-CSF, rmGM-CSF and rmIFN-gamma as
      single agents and sequential therapy with rmM-CSF + (rmIL-12 and/or rmIL-18) +
      rmIFN-gamma in addition to ampicillin were not associated with increased
      survival. However, prophylactic single doses of rmIL-12, rmIL-18, rmM-CSF and
      rmIFN-gamma and prophylactic sequential doses of rmM-CSF + (rmIL-12 and/or rmIL
      18) + rmIFN-gamma in addition to ampicillin were associated with significantly
      enhanced survival compared with ampicillin alone. CONCLUSIONS: These data suggest
      prophylactic administration of macrophage and Th1 immunoregulatory cytokines can
      potentially overcome deficits in neonatal immunity to protect against Lm.

PMID- 24911894
TI  - Two-dose varicella vaccine effectiveness and rash severity in outbreaks of
      varicella among public school students.
AB  - BACKGROUND: Universal 2-dose varicella vaccination was recommended in 2006 to
      further reduce varicella disease burden. This study examined 2-dose varicella
      vaccine effectiveness (VE) and rash severity in the setting of school-associated
      varicella outbreaks. METHODS: A case control study was conducted from January
      2010 to May 2011 in all West Virginia public schools. Clinically diagnosed cases
      from varicella outbreaks were matched with classmate controls. Vaccination
      information was collected from school, health department and healthcare provider
      immunization information systems. RESULTS: Among the 133 cases and 365 controls
      enrolled, VE against all varicella was 83.2% [95% confidence interval (CI): 69.2%
      90.8%] for 1-dose of varicella vaccine and 93.9% (95% CI: 86.9%-97.1%) for 2
      dose; the incremental VE (2-dose vs. 1-dose) was 63.6% (95% CI: 32.6%-80.3%). In
      preventing moderate/severe varicella, 1-dose varicella vaccine was 88.2% (95% CI:
      72.7%- 94.9%) effective, and 2-dose vaccination was 97.5% (95% CI: 91.6%-99.2%)
      effective, with the incremental VE of 78.6% (95% CI: 40.9%-92.3%). One-dose VE
      declined along with time since vaccination (VE = 93.0%, 88.0% and 81.8% in <5, 5
      9 and >= 10 years after vaccination, P = 0.001 for trend). Both 1- and 2-dose
      breakthrough cases had milder rash than unvaccinated cases (<50 lesion: 24.6%,
      49.1% and 70.0% in unvaccinated, 1-dose and 2-dose cases, P < 0.001), and no
      severe disease was found in 2-dose cases. CONCLUSIONS: Two-dose varicella
      vaccination is highly effective and confers higher protection than a 1-dose
      regimen. High 2-dose varicella vaccination coverage should maximize the benefits
      of the varicella vaccination program and further reduce varicella disease burden
      in the United States.

PMID- 24911895
TI  - Emergence of Streptococcus pneumoniae serogroups 15 and 35 in nasopharyngeal
      cultures from young children with acute otitis media.
AB  - BACKGROUND: Surveillance of children with acute otitis media (AOM) for
      nasopharyngeal colonization with Streptococcus pneumoniae before, during and
      after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7)
      indicated the near-complete elimination of PCV7 strains and the emergence of
      pneumococcal serotype 19A. METHODS: To determine effects of the introduction of
      13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal nasopharyngeal
      colonization, we obtained nasopharyngeal cultures from 228 children 6 through 23
      of age months presenting with a new episode of AOM during 2012 and 2013 and
      enrolled in an ongoing clinical trial of antimicrobial efficacy. All children had
      received at least 2 doses of PCV13. The S. pneumoniae isolates were subjected to
      serotyping and testing for antimicrobial susceptibility. We compared the findings
      with results obtained in 3 earlier studies. RESULTS: We found nasopharyngeal
      colonization with S. pneumoniae in 113 (50%) of the children with AOM. PCV7 and
      PCV13 serotypes accounted for 2% and 12%, respectively, of the pneumococcal
      isolates. Of the 14 PCV13 isolates, 8 were serotype 19A. Nonvaccine serotypes
      accounted for 69% of the isolates. Most frequently occurring were subtypes of
      serotype 15 (23%) and serotype 35B (9%). Overall, 33% of the isolates were
      penicillin nonsusceptible, a proportion not significantly different from
      proportions found in our 3 earlier studies (26%, 36% and 37%, respectively).
      Serotypes 15 and 35B accounted for 51% of penicillin-nonsusceptible isolates.
      CONCLUSIONS: Expansion of contents of pneumococcal vaccine administered to
      children is followed by not-fully-predictable changes in nasopharyngeal
      pneumococcal colonization. Continued surveillance is required to help inform
      future vaccine development.

PMID- 24911896
TI  - Antibody persistence after primary and booster doses of a quadrivalent
      meningococcal conjugate vaccine in adolescents.
AB  - BACKGROUND: The aim of this study was to evaluate antibody persistence 5 years
      after primary vaccination with the quadrivalent meningococcal conjugate vaccines
      MenACWY-CRM or MenACWY-D and 2 years after a booster dose of MenACWY-CRM, in the
      context of a phase 3 study. METHODS: Subjects (aged 19.2 +/- 2.3 years) were
      assigned to 5 groups according to whether they had previously received primary
      vaccination (at 14.2 +/- 2.2 years) with MenACWY-CRM (N = 131) or MenACWY-D (N =
      76), a booster dose of MenACWY-CRM 3 years after primary vaccination with MenACWY
      CRM (N = 44) or MenACWY-D (N = 31) or no vaccination (N = 107). The
      immunogenicity measures were percentages of subjects with serum bactericidal
      activity (hSBA) >= 1:8 for serogroups A, C, W and Y and hSBA geometric mean
      titers. Comparisons with age-matched, vaccine-naive subjects were performed.
      RESULTS: A majority of subjects vaccinated 5 years previously maintained hSBA >=
      1:8 against serogroups C, W and Y in the MenACWY-CRM (59%-82%) and MenACWY-D
      groups (54%-73%); this was lower for serogroup A in both groups. There was a
      decline in antibody titers after primary vaccination, especially in the first 2
      years postprimary vaccination, with steady concentrations during the next 3
      years. Two years after MenACWY-CRM booster vaccination the percentages of
      subjects with hSBA >= 1:8 ranged from 77% to 100% across serogroups and geometric
      mean titers were 2.5- to 8-fold higher than prebooster values across serogroups.
      CONCLUSIONS: Booster vaccination with MenACWY-CRM elicited a robust immune
      response during the 2-year follow-up period, irrespective of previous
      vaccination.

PMID- 24911897
TI  - Impact of rotavirus vaccination in Germany: rotavirus surveillance,
      hospitalization, side effects and comparison of vaccines.
AB  - BACKGROUND: Although rotavirus (RV) vaccination was licensed in 2006, it was not
      included into the officially recommended German childhood vaccination schedule
      until 2013. Local differences in health policies in the past led to large
      differences in vaccination coverage rate among the federal states of Germany.
      This enables an ecologic study of RV vaccine effectiveness. METHODS: We performed
      a population-based retrospective analysis of RV vaccination use, RV notification
      and hospitalization among 0 to 5-year-old children in Germany during 2006 to
      2011/2012. We compared effectiveness of the 2 RV vaccines, Rotateq and Rotarix,
      in an ambulatory setting and analyzed potential side effects. RESULTS: We
      observed a significant reduction in RV notifications since introduction of RV
      vaccination. In areas attaining vaccine coverage of 64%, RV-related hospital
      admissions of 0 and 1-year-old children decreased by 60% compared with 19%
      reduction in the low vaccination coverage area. Decrease in RV-related
      hospitalizations of 0 and 1-year-old children was specific and significantly
      associated with vaccination coverage of the individual federal state (P < 0.0001,
      r = -0.68). There was no overall increase in intussusception rate or Kawasaki
      disease-related hospital admissions since introduction of RV vaccination. The 2
      licensed RV vaccines had similar effectiveness in the ambulatory setting.
      CONCLUSIONS: Postmarketing data suggest that RV vaccination is efficient in
      reducing RV-related hospitalizations. There is no apparent difference in
      effectiveness for Rotarix and Rotateq.

PMID- 24911898
TI  - Insights into pediatric herpes simplex encephalitis from a cohort of 21 children
      from the California Encephalitis Project, 1998-2011.
AB  - Twenty-one children with confirmed herpes simplex encephalitis were identified in
      the California Encephalitis Project.Noteworthy features included 6 (29%) patients
      with an initial negative herpes simplex virus cerebrospinal fluid polymerase
      chain reaction test and 13 (62%) patients with extratemporal lobe involvement
      identified by neuroimaging [corrected]. Eleven cases were <4 years of age, but
      all 4 fatal cases occurred in adolescents.

PMID- 24911899
TI  - A new suture technique avoids rib fractures and intercostal nerve trauma in
      thoracotomy.
AB  - This article describes an alternative suture technique for thoracotomy incisions.
      A modified mattress suture technique is used to fix the intercostal muscles. The
      described technique can prevent rib fractures and reduce the incidence of
      intercostal nerve injury. Also, this technique is easy to perform and is
      effective. 

PMID- 24911900
TI  - Anomalous Origin of Right Coronary Artery from Left Coronary Sinus: Surgical
      Management and Clinical Result.
AB  - BACKGROUND: Anomalous aortic origin of coronary artery is a rare congenital
      condition in which the coronary artery arises from the opposite sinus of
      Valsalva. Although many patients are asymptomatic at the time of presentation or
      diagnosis, surgical correction is recommended due to the risk of ischemic sudden
      death. We describe seven cases of right coronary artery (RCA) arising from the
      left sinus of Valsalva, causing the hypoperfusion through RCA. PATIENTS AND
      METHODS: All patients underwent preoperative coronary angiography,
      echocardiography, and cardiac stress test (treadmill test [TMT], n = 4;
      technetium-99m sestamibi [MIBI], n = 3). In four patients, coronary computed
      tomography (CT) was performed. On the basis of preoperative test results,
      unroofing of the coronary artery (n = 3) or off-pump coronary artery bypass
      (OPCAB; n = 4; patients with coronary arterial occlusive disease) was performed.
      In two patients, intraoperative flow meter was performed and showed the
      improvement of flow rate through RCA. RESULTS: Postoperative CT angiography after
      OPCAB confirmed good graft patency (n = 4); CT angiography after unroofing
      demonstrated widely patent neo-orifice (n = 3). All patients underwent
      postoperative cardiac stress tests including TMT and MIBI, which revealed no
      evidence of ischemia. All patients were asymptomatic and returned to normal
      activities (mean follow-up, 41 months; 32-49 months). CONCLUSION: The appropriate
      surgical procedure based on specific anatomical details, perioperative
      evaluation, and follow-up by focusing on the ischemia may lead to successful
      surgical outcomes of this coronary anomaly.

PMID- 24911901
TI  - Successful use of a left ventricular apical access and closure device for second
      generation transapical aortic valve implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become routine for
      the treatment of high-risk patients with aortic stenosis. We assessed safety and
      feasibility of a left ventricular apical access and closure device combined with
      second-generation transapical (TA) TAVI transcatheter heart valves (THV). METHODS
      AND RESULTS: Three elderly, comorbid patients (logEuroSCORE I 13.0-31.1%)
      received transapical aortic valve implantation (TA-AVI) via the Apica ASC device
      (Apica Cardiovascular Ltd., Galway, Ireland) using second-generation THV
      (Medtronic Engager [Medtronic 3F Therapeutics, Santa Ana, California, United
      States], JenaValve [JenaValve Technology GmbH, Munich, Germany], Symetis Acurate
      [Symetis S.A., Ecublens, Switzerland]). Access was gained using a non-rib
      spreading technique and a novel access and closure device. THV deployment was
      successful with excellent hemodynamic outcome (no PVL, n = 2; trace PVL, n = 1;
      mean transvalvular gradients, 5-19 mm Hg) and complete apical hemostasis. No
      periprocedural major adverse events occurred and Valve Academic Research
      Consortium-2-defined composite end point of device success was met in all cases.
      CONCLUSION: Safety and feasibility of TA-AVI using the ASC device with second
      generation THV was demonstrated. Combining latest available technology is a major
      step toward improved functional outcome and decreased surgical trauma in TA-AVI.
      Potentially, technical enhancements may eventually pave the way toward a fully
      percutaneous TA-AVI procedure.

PMID- 24911902
TI  - Outcome after preoperative or intraoperative use of intra-arterial urokinase
      thrombolysis for acute popliteal artery thrombosis and leg ischemia.
AB  - OBJECTIVES: To evaluate the outcome of acute popliteal artery aneurysm (PAA)
      thrombosis and leg ischemia after preoperative or intraoperative use of intra
      arterial urokinase thrombolysis. MATERIALS AND METHODS: From 2000 to 2009, 86
      patients with acute leg ischemia (Rutherford grade IB to IIA) from PAA thrombosis
      were treated by immediate surgery including intraoperative thrombolysis (group A:
      47 cases) or preoperative thrombolysis (group B: 39 cases) followed by acute (<24
      hours) or elective surgery. Chi-square tests for categorical data and time to
      event provided two-sided p values with a level of significance at 0.05 and all
      confidence intervals (CIs) at the 95% level. RESULTS: The mean follow-up was 45
      months. The 2-year primary patency was 61.7% (29/47) for group A and 43.6%
      (17/39) for group B (hazard ratio [HR] 1.85; 95% CI: 0.96 to 3.54; p = 0.06). The
      2-year secondary patency was 70.2% (33/47) for group A and 53% (21/39) for group
      B (HR 1.86; 95% CI: 0.91 to 3.81; p = 0.08). One-month amputation rate was 18% in
      group A and 29% in group B (p < 0.001), and 12-month amputation rate was 19%
      (9/47) in group A and 44% (17/39) in B (p = 0.05). In group A, 28% of patients
      required fasciotomy and in group B, 59% (p < 0.05). Effective thrombolysis
      allowed 82% limb salvage patency in group B. No systemic or locoregional
      complications during thrombolysis were recorded, but four cases of worsening
      ischemia were recorded. CONCLUSION: Our results suggest that the immediate
      surgery with intraoperative thrombolysis improved the outcome of patients with
      acute leg ischemia due to PAA thrombosis in terms of limb salvage.

PMID- 24911903
TI  - Conditions for liposome adsorption and bilayer formation on BSA passivated solid
      supports.
AB  - Planar solid supported lipid membranes that include an intervening bovine serum
      albumen (BSA) cushion can greatly reduce undesirable interactions between
      reconstituted membrane proteins and the underlying substrate. These hetero-self
      assemblies reduce frictional coupling by shielding reconstituted membrane
      proteins from the strong surface charge of the underlying substrate, thereby
      preventing them from strongly sticking to the substrate themselves. The
      motivation for this work is to describe the conditions necessary for liposome
      adsorption and bilayer formation on these hetero-self-assemblies. Described here
      are experiments that show that the state of BSA is critically important to
      whether a lipid bilayer is formed or intact liposomes are adsorbed to the BSA
      passivated surface. It is shown that a smooth layer of native BSA will readily
      promote lipid bilayer formation while BSA that has been denatured either
      chemically or by heat will not. Atomic force microscopy (AFM) and fluorescence
      microscopy was used to characterize the surfaces of native, heat denatured, and
      chemically reduced BSA. The mobility of several zwitterionic and negatively
      charged lipid combinations has been measured using fluorescence recovery after
      photobleaching (FRAP). From these measurements diffusion constants and percent
      recoveries have been determined and tabulated. The effect of high concentrations
      of beta-mercaptoethanol (beta-ME) on liposome formation as well as bilayer
      formation was also explored. 

PMID- 24911904
TI  - Transfusion CME hits 50.

PMID- 24911905
TI  - "Do you catch my drift?".

PMID- 24911906
TI  - Can a comparative database study help to develop an effective risk index system?

PMID- 24911907
TI  - Schistocytes.

PMID- 24911908
TI  - Fresh-frozen plasma should not be given to nonbleeding premature infants with
      "abnormal" coagulation tests.

PMID- 24911909
TI  - In reply.

PMID- 24911910
TI  - Parvovirus B19 genotype 2 in blood donations.

PMID- 24911911
TI  - Does transfusion of salvaged blood products have a significant impact on
      coagulation?

PMID- 24911912
TI  - Vitamin B12 status and the effects of vitamin B12 supplementation during the
      first year of life of spring calves from pasture-fed dairy herds.
AB  - AIMS: To determine the vitamin B12 status of dairy calves during their first year
      of life, and to evaluate the benefits of vitamin B12 supplementation. METHODS: In
      Experiment I, 20 17-day-old heifer calves from the AgResearch Flock House herd
      were monitored until 198 days old. On Days 0 and 90 of the study, half of the
      animals received an injection of microencapsulated vitamin B12 at 0.12 mg/kg
      bodyweight. All received colostrum, milk replacer and calf meal, with ad libitum
      access to pasture. At regular intervals the calves were weighed and serum
      collected for vitamin B12 measurement. In Experiment II at Flock House and the
      adjacent Landcorp Tangimoana station, 80 150-day-old heifer calves were monitored
      until 342 days old. On Days 0 and 97, half of the animals received vitamin B12 as
      per Experiment I. At regular intervals samples were collected from 12 calves per
      group, to determine concentrations of vitamin B12 in serum. RESULTS: Mean
      concentration of vitamin B12 in milk replacer was 63 (SE 4) ug/kg dry matter
      (DM). Cobalt concentrations in calf meal were 0.45-1.58 and 0.07-0.28 mg/kg DM in
      pastures. From 17 to 198 days of age (Experiment I) mean concentrations of
      vitamin B12 in serum of the control group decreased from 119 (SE 8) to 57 (SE 5)
      pmol/L. From 150 to 342 days of age (Experiment II), overall mean concentrations
      of the control groups at Flock House and Tangimoana were 90 (SE 2) and 96 (SE 3)
      pmol/L, respectively. Vitamin B12 injections increased (p<0.001) serum
      concentrations for at least 90 days, with peak concentrations of 323 (SE 23)
      (Experiment I) and 520 (SE 22) (Experiment II) pmol/L reached 28-35 days after
      each injection. Liveweight gain was not increased by supplementation and there
      was no difference in final liveweight between groups. CONCLUSIONS: Concentrations
      of vitamin B12 in serum of unsupplemented calves prior to weaning indicated their
      vitamin B12 status was adequate due to the vitamin B12 and Co content of the milk
      replacer, and calf meal. Concentrations decreased during the transition to a
      pasture-based diet. Supplementation increased concentrations of vitamin B12 in
      serum but did not improve liveweight gains. CLINICAL RELEVANCE: Under this calf
      rearing system, vitamin B12 deficiency is unlikely to occur prior to weaning, and
      vitamin B12 supplementation is unlikely to increase growth rates of grazing
      calves when concentrations of vitamin B12 in serum are > 90 pmol/L.

PMID- 24911913
TI  - p53 vs. ISG15: stop, you're killing me.

PMID- 24911914
TI  - Implication of Smad2 and Smad3 in transforming growth factor-beta-induced
      posterior capsular opacification of human lens epithelial cells.
AB  - PURPOSE: Transforming growth factor-beta2 (TGF-beta2) is a potent inducer of
      posterior capsular opacification (PCO), a critical Smad-dependent event. This
      study was conducted to investigate the contributions of Smad2 and Smad3 to PCO
      development based on selective over-expression of either Smad2 or Smad3. METHODS:
      We selectively activated the TGF-beta/Smad pathway in cell lines transfected with
      expression plasmids containing Smad2 or Smad3. These cell lines were then
      analyzed to determine the individual contributions of Smad2 and Smad3 to TGF
      beta2 treatment response in an in vitro culture of HLE B-3 cells. The effects of
      Smad2 and Smad3 on cell viability were assessed by MTT and flow cytometry assay.
      A transwell assay was used to observe the role of Smad2 and Smad3 in the
      migration of HLE B-3 cells. Western blotting, real-time PCR, and
      immunocytofluorescence staining were performed to detect the accumulation of ECM
      proteins and EMT in response to selective Smad2 or Smad3 activation. The presence
      of soluble collagen I, and fibronectin in the culture medium supernatant were
      detected by ELISA. RESULTS: Selective Smad3 activation via gene transfection
      enhanced TGF-beta2-responsive growth inhibition and apoptosis. Transwell assay
      results showed that TGF-beta2-induced cell migration was Smad2 dependent and
      Smad3 independent. Analysis by Western blot, RT-PCR and ELISA demonstrated that
      the determinant factor in ECM secretion was Smad3 signaling rather than Smad2
      signaling. Western blot and RT-PCR showed that the loss of E-Cadherin and
      acquisition of alpha-SMA, the hallmark of epithelial-mesenchymal transition
      (EMT), were both reliant on Smad2 signaling. Immunocytofluorescence staining
      confirmed the role of Smad2 in the accumulation of alpha-SMA. CONCLUSIONS: Smad2
      and Smad3 are both necessary for the formation of PCO. The discovery of
      additional TGF-beta2/Smad signaling mechanisms may provide potential therapeutic
      targets to help combat PCO.

PMID- 24911916
TI  - Inadequacy of clinical trial designs and data to control for the confounding
      impact of race/ethnicity in response to treatment in multiple sclerosis.

PMID- 24911917
TI  - Pressure-induced changes in interdiffusivity and compressive stress in chemically
      strengthened glass.
AB  - Glass exhibits a significant change in properties when subjected to high pressure
      because the short- and intermediate-range atomic structures of glass are tunable
      through compression. Understanding the link between the atomic structure and
      macroscopic properties of glass under high pressure is an important scientific
      problem because the glass structures obtained via quenching from elevated
      pressure may give rise to properties unattainable under standard ambient pressure
      conditions. In particular, the chemical strengthening of glass through K(+)-for
      Na(+) ion exchange is currently receiving significant interest due to the
      increasing demand for stronger and more damage-resistant glass. However, the
      interplay among isostatic compression, pressure-induced changes in alkali
      diffusivity, compressive stress generated through ion exchange, and the resulting
      mechanical properties are poorly understood. In this work, we employ a specially
      designed gas pressure chamber to compress bulk glass samples isostatically up to
      1 GPa at elevated temperature before or after the ion exchange treatment of a
      commercial sodium-magnesium aluminosilicate glass. Compression of the samples
      prior to ion exchange leads to a decreased Na(+)-K(+) interdiffusivity, increased
      compressive stress, and slightly increased hardness. Compression after the ion
      exchange treatment changes the shape of the potassium-sodium diffusion profiles
      and significantly increases glass hardness. We discuss these results in terms of
      the underlying structural changes in network-modifier environments and overall
      network densification. 

PMID- 24911915
TI  - Mutational analysis of the Ve1 immune receptor that mediates Verticillium
      resistance in tomato.
AB  - Pathogenic Verticillium species are economically important plant pathogens that
      cause vascular wilt diseases in hundreds of plant species. The Ve1 gene of tomato
      confers resistance against race 1 strains of Verticillium dahliae and V. albo
      atrum. Ve1 encodes an extracellular leucine-rich repeat (eLRR) receptor-like
      protein (RLP) that serves as a cell surface receptor for recognition of the
      recently identified secreted Verticillium effector Ave1. To investigate
      recognition of Ave1 by Ve1, alanine scanning was performed on the solvent exposed
      beta-strand/beta-turn residues across the eLRR domain of Ve1. In addition,
      alanine scanning was also employed to functionally characterize motifs that
      putatively mediate protein-protein interactions and endocytosis in the
      transmembrane domain and the cytoplasmic tail of the Ve1 protein. Functionality
      of the mutant proteins was assessed by screening for the occurrence of a
      hypersensitive response upon co-expression with Ave1 upon Agrobacterium
      tumefaciens-mediated transient expression (agroinfiltration). In order to confirm
      the agroinfiltration results, constructs encoding Ve1 mutants were transformed
      into Arabidopsis and the transgenes were challenged with race 1 Verticillium. Our
      analyses identified several regions of the Ve1 protein that are required for
      functionality. 

PMID- 24911918
TI  - Agreement attraction during comprehension of grammatical sentences: ERP evidence
      from ellipsis.
AB  - Successful dependency resolution during language comprehension relies on
      accessing certain representations in memory, and not others. We recently reported
      event-related potential (ERP) evidence that syntactically unavailable,
      intervening attractor-nouns interfered during comprehension of Spanish noun
      phrase ellipsis (the determiner otra/otro): grammatically correct determiners
      that mismatched the gender of attractor-nouns elicited a sustained negativity as
      also observed for incorrect determiners (Martin, Nieuwland, & Carreiras, 2012).
      The current study sought to extend this novel finding in sentences containing
      object-extracted relative clauses, where the antecedent may be less prominent.
      Whereas correct determiners that matched the gender of attractor-nouns now
      elicited an early anterior negativity as also observed for mismatching
      determiners, the previously reported interaction pattern was replicated in P600
      responses to subsequent words. Our results suggest that structural and gender
      information is simultaneously taken into account, providing further evidence for
      retrieval interference during comprehension of grammatical sentences. 

PMID- 24911919
TI  - Theta-band phase tracking in the two-talker problem.
AB  - It is usually easy to understand speech, but when several people are talking at
      once it becomes difficult. The brain must select one speech stream and ignore
      distracting streams. We tested a theory about the neural and computational
      mechanisms of attentional selection. The theory is that oscillating signals in
      brain networks phase-lock with amplitude fluctuations in speech. By doing this,
      brain-wide networks acquire information from the selected speech, but ignore
      other speech signals on the basis of their non-preferred dynamics. Two
      predictions were supported: first, attentional selection boosted the power of
      neuroelectric signals that were phase-locked with attended speech, but not
      ignored speech. Second, this phase selectivity was associated with better recall
      of the attended speech. 

PMID- 24911920
TI  - Scalp and cranial vault fulminant relapse from an endometrial carcinoma.

PMID- 24911921
TI  - Flame oxidation of stainless steel felt enhances anodic biofilm formation and
      current output in bioelectrochemical systems.
AB  - Stainless steel (SS) can be an attractive material to create large electrodes for
      microbial bioelectrochemical systems (BESs), due to its low cost and high
      conductivity. However, poor biocompatibility limits its successful application
      today. Here we report a simple and effective method to make SS electrodes
      biocompatible by means of flame oxidation. Physicochemical characterization of
      electrode surface indicated that iron oxide nanoparticles (IONPs) were generated
      in situ on an SS felt surface by flame oxidation. IONPs-coating dramatically
      enhanced the biocompatibility of SS felt and consequently resulted in a robust
      electroactive biofilm formation at its surface in BESs. The maximum current
      densities reached at IONPs-coated SS felt electrodes were 16.5 times and 4.8
      times higher than the untreated SS felts and carbon felts, respectively.
      Furthermore, the maximum current density achieved with the IONPs-coated SS felt
      (1.92 mA/cm(2), 27.42 mA/cm(3)) is one of the highest current densities reported
      thus far. These results demonstrate for the first time that flame oxidized SS
      felts could be a good alternative to carbon-based electrodes for achieving high
      current densities in BESs. Most importantly, high conductivity, excellent
      mechanical strength, strong chemical stability, large specific surface area, and
      comparatively low cost of flame oxidized SS felts offer exciting opportunities
      for scaling-up of the anodes for BESs. 

PMID- 24911922
TI  - Child sexual abuse in Madurai, India: a literary review and empirical study.
AB  - This article attempts to explore the cultural and patriarchal relevance of child
      sexual abuse in a conservative town in India, with a special interest in
      understanding the current problems experienced by teenage girls in India. A
      questionnaire was distributed to 100 respondents who belonged to Thiagarajar
      College of Engineering, Thiruparangundram, Madurai. The questionnaire was
      developed with special reference to the female protagonist, Lily in Jaishree
      Misra's Secrets and Lies. The resulting article also includes an e-interview with
      Jaishree Misra. The researchers hypothesize that change can be envisioned when
      the social conscience is awakened to cruel events that happen in the Indian
      population. Change regarding social events must go even further to allow children
      to blossom and experience the joys of childhood. 

PMID- 24911923
TI  - Use of yoked prisms in patients with acquired brain injury: a retrospective
      analysis.
AB  - PRIMARY OBJECTIVE: The purpose of this retrospective study was to determine the
      clinical practices for prescribing yoked prisms, as well as to assess related
      patient responses, in a sample of visually-symptomatic patients having acquired
      brain injury (ABI). METHODS: The clinical records of individuals with acquired
      brain injury (ABI) that were assessed for yoked prisms were reviewed
      retrospectively. This query resulted in 60 patient records for analysis between
      January 2011 and December 2012. The following diagnostic groups were analysed:
      homonymous hemianopsia (HH)/homonymous quadranopsia, abnormal egocentric
      localization (AEL) and visual neglect. RESULTS: HH/homonymous quadranopsia
      (58.3%) was the primary indication to prescribe yoked prisms, followed by visual
      neglect/unilateral spatial inattention (USI) (40.0%) and AEL (11.7%). The most
      common favourable patient responses were increased awareness of their blind
      visual field and improved gait, mobility and balance. The magnitude and direction
      of prisms prescribed were dependent upon the subjective responses in patients
      manifesting AEL. In contrast, base direction was dependent upon the direction of
      visual field loss in patients with HH/homonymous quadranopsia and visual neglect.
      CONCLUSIONS: Two-thirds of the present sample population responded favourably to
      the yoked prisms. The results of the present study should prove useful to
      clinicians for the successful prescription of yoked prisms as a treatment
      modality in patients presenting with the above three diagnoses.

PMID- 24911924
TI  - The latest review on the polyphenols and their bioactivities of Chinese Morus
      plants.
AB  - The mulberry tree (Morus alba) plays a key role in agriculture, and its different
      parts have been used as popular Traditional Chinese Medicines for thousands of
      years. There are 16 species belonging to the Morus genus. Among them, 11 species
      distribute in China, most of which have been used as the substitutes of M. alba
      in local provinces. This review summarizes the structural characters of
      polyphenols, the main components in Morus, including Diels-Alder-type adducts,
      flavonoids, 2-arylbenzofurans, and stilbenes, and also their related
      bioactivities in the last 10 years. 

PMID- 24911925
TI  - Moving receptor redirected adoptive cell therapy toward fine tuning of antitumor
      responses.
AB  - Adoptive cell transfer (ACT) is emerging as a powerful modality of cancer
      treatment. While ACT has proved able to induce massive clinical responses,
      genetic modification of T lymphocytes further improved clinical responses
      obtained. One of the major current limitations of ACT is the inability to discern
      healthy from malignant cells, leading to on target/off tumor responses that can
      limit its application. We here discuss some of the approaches currently under
      development and potential solutions to circumvent these limitations and extend
      this potentially curative therapy to different tumors by targeting a variety of
      antigens. 

PMID- 24911926
TI  - Effects of diet and strain on mouse serum and tissue retinoid concentrations.
AB  - The relationship between dietary vitamin A and all-trans-retinoic acid levels in
      serum and tissues had not been quantified. We determined the impact of dietary
      vitamin A on retinoid levels in serum, liver, kidney, testis, and epididymal
      white adipose of five mouse strains: AKR/J; BALB/cByJ; C3H/HeJ; C57BL/6J;
      129S1/SvImJ. Retinoids were quantified in mice fed copious vitamin A (lab chow,
      >=20 IU/g) followed by one month feeding a vitamin A-sufficient diet (4 IU/g), or
      after three generations of feeding a vitamin A-sufficient diet. Retinol and
      retinyl esters were measured by high-performance liquid chromatography with
      ultraviolet absorbance detection. All-trans-retinoic acid was quantified by
      liquid chromatography tandem mass spectrometry. The amounts of dietary vitamin A
      had long-term strain-specific effects on tissue retinyl ester, retinol and all
      trans-retinoic acid concentrations. Three generations of feeding a vitamin A
      sufficient diet decreased all-trans-retinoic acid in most tissues of most
      strains, in some cases more than 60%, compared to a diet with copious vitamin A.
      With both diets, all-trans-retinoic acid concentrations maintained an order of
      liver ~ testis > kidney > white adipose tissue ~ serum. Neither retinol nor all
      trans-retinoic acid in serum reflected all-trans-retinoic acid concentrations in
      tissues. Strain and tissue-specific differences in retinol and all-trans-retinoic
      acid altered by different amounts of dietary vitamin A could have profound
      effects on retinoid action. This would be the case especially with the increased
      all-trans-retinoic acid values associated with the amounts of vitamin A and its
      precursors (carotenoids) in chow diets. 

PMID- 24911928
TI  - Managing heat and immune stress in athletes with evidence-based strategies.
AB  - Heat and immune stress can affect athletes in a wide range of sports and
      environmental conditions. The classical thermoregulatory model of heat stress has
      been well characterized, as has a wide range of practical strategies largely
      centered on cooling and heat-acclimation training. In the last decade evidence
      has emerged of an inflammatory pathway that can also contribute to heat stress.
      Studies are now addressing the complex and dynamic interplay between
      hyperthermia, the coagulation cascade, and a systemic inflammatory response
      occurring after transient damage to the gastrointestinal tract. Damage to the
      intestinal mucosal membrane increases permeability, resulting in leakage of
      endotoxins into the circulation. Practical strategies that target both
      thermoregulatory and inflammatory causes of heat stress include precooling; short
      term heat-acclimation training; nutritional countermeasures including hydration,
      energy replacement, and probiotic supplementation; pacing strategies during
      events; and postevent cooling measures. Cooperation between international,
      national, and local sporting organizations is required to ensure that heat
      management policies and strategies are implemented effectively to promote
      athletes' well-being and performance. 

PMID- 24911927
TI  - Heparin responses in vascular smooth muscle cells involve cGMP-dependent protein
      kinase (PKG).
AB  - Published data provide strong evidence that heparin treatment of proliferating
      vascular smooth muscle cells results in decreased signaling through the ERK
      pathway and decreases in cell proliferation. In addition, these changes have been
      shown to be mimicked by antibodies that block heparin binding to the cell
      surface. Here, we provide evidence that the activity of protein kinase G is
      required for these heparin effects. Specifically, a chemical inhibitor of protein
      kinase G, Rp-8-pCPT-cGMS, eliminates heparin and anti-heparin receptor antibody
      effects on bromodeoxyuridine incorporation into growth factor-stimulated cells.
      In addition, protein kinase G inhibitors decrease heparin effects on ERK
      activity, phosphorylation of the transcription factor Elk-1, and heparin-induced
      MKP-1 synthesis. Although transient, the levels of cGMP increase in heparin
      treated cells. Finally, knock down of protein kinase G also significantly
      decreases heparin effects in growth factor-activated vascular smooth muscle
      cells. Together, these data indicate that heparin effects on vascular smooth
      muscle cell proliferation depend, at least in part, on signaling through protein
      kinase G.

PMID- 24911929
TI  - Lessons from 28 cases of reconstruction by lenticular island pedicle flap at a
      single institution.
AB  - BACKGROUND: Lenticular island pedicle flap (LIPF) has been reported to be one of
      the most useful techniques for reconstructing middle cheek skin defects. LIPF may
      have been used all over the world on a daily basis; however, no reports have
      examined a large number of LIPF cases at a single institution. MATERIALS AND
      METHODS: A total of 28 cases of reconstruction by LIPF at the Hokkaido University
      Hospital from 2005 to 2013 were analysed. We examined the tumour type, location,
      area of defect and presence/absence of antithrombotic treatment and
      complications, including transient circulatory impairment, damage to facial
      nerves and eyelid ectropion. RESULTS: We found that nine patients had transiently
      impaired circulation. This complication was statistically more frequent in the
      patients without antithrombotic treatment than in the patients with
      antithrombotic treatment (0/8 vs. 10/20, P = 0.0292; Fisher's exact test).
      CONCLUSION: We revelled that LIPF have been safely performed even under
      antithrombotic treatment, so, when patients are taking antithrombotic agents, we
      should choose LIPF rather than conventional flap including cheek flap, island
      pedicle flap and so on.

PMID- 24911930
TI  - Retinal and choroidal thickness in children with familial Mediterranean fever.
AB  - PURPOSE: The aim of the present study was to evaluate retinal and choroidal
      thicknesses in children with familial Mediterranean fever (FMF). METHODS: Thirty
      patients with FMF and 28 healthy controls were included in the study. The
      thicknesses of the retina and choroid of each subject's right eye were measured
      at the fovea and horizontal nasal and temporal quadrants at 500-um intervals to
      1500 um from the foveal center using spectral-domain optic coherence tomography.
      RESULTS: Retinal and choroidal thicknesses at the fovea did not differ between
      groups (p = 0.32 and p = 0.39, respectively). Horizontal nasal and temporal
      retinal and choroidal thickness measurements at 500-um intervals to a distance of
      1500 um from the foveal center were also similar between the groups (all p >
      0.05). CONCLUSIONS: The retinal and choroidal thicknesses of children with FMF do
      not differ from those of age- and sex-matched healthy controls.

PMID- 24911933
TI  - Interaction of parental KIR and fetal HLA-C genotypes with the risk of
      preeclampsia.
AB  - OBJECTIVE: The aim of this study is to investigate whether certain combination of
      maternal killer cell immunoglobulin-like receptors (KIR) and fetal human
      leukocyte antigen-C (HLA-C) is risk for preeclampsia in the Chinese Han
      population. METHODS: A case-control study was conducted in 47 pregnant women with
      preeclampsia and 54 normal pregnant women. Twelve KIR genes were genotyped by PCR
      sequence-specific primer in mothers. High-resolution HLA-C genotyping was
      performed in couples and fetuses by a routine sequencing-based typing method.
      RESULTS: The frequency of KIR2DS1 was decreased (p = 0.028) and AA genotype was
      increased (p = 0.017) in preeclampsia compared with controls. More women with KIR
      AA genotype have fewer C2 genes than their fetuses in preeclampsia than controls.
      CONCLUSION: Women with KIR AA genotype and fewer C2 genes than their fetuses were
      at risk for preeclampsia in the Chinese Han population, supporting that maternal
      fetal KIR-HLA-C interaction plays an important role in preeclampsia development.

PMID- 24911932
TI  - Chloroplast transformation of Platymonas (Tetraselmis) subcordiformis with the
      bar gene as selectable marker.
AB  - The objective of this research was to establish a chloroplast transformation
      technique for Platymonas (Tetraselmis) subcordiformis. Employing the gfp gene as
      a reporter and the bar gene as a selectable marker, transformation vectors of P.
      subcordiformis chloroplast were constructed with endogenous fragments rrn16S-trnI
      (left) and trnA-rrn23S (right) as a recombination site of the chloroplast genome.
      The plasmids were transferred into P. subcordiformis via particle bombardment.
      Confocal laser scanning microscopy indicated that the green fluorescence protein
      was localized in the chloroplast of P. subcordiformis, confirming the activity of
      the Chlamydomonas reinhardtii promoter. Cells transformed with the bar gene were
      selected using the herbicide Basta. Resistant colonies were analyzed by PCR and
      Southern blotting, and the results indicated that the bar gene was successfully
      integrated into the chloroplast genome via homologous recombination. The
      technique will improve genetic engineering of this alga. 

PMID- 24911934
TI  - Fluorine effects in organocatalysis - asymmetric Bronsted acid assisted Lewis
      base catalysis for the synthesis of trifluoromethylated heterocycles exploiting
      the negative hyperconjugation of the CF3-group.
AB  - An efficient Bronsted acid assisted Lewis base catalysis protocol for the
      synthesis of enantiomerically pure trifluoromethylated dihydropyridazines
      starting from readily available hydrazones and alpha,beta-unsaturated aldehydes
      has been developed. The reaction exhibits high tolerance towards many functional
      groups and is applicable to various aliphatic, aromatic and hetero-aromatic
      alpha,beta-unsaturated aldehydes, and provides the products in good yields and
      with excellent enantioselectivities. 

PMID- 24911931
TI  - 3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1
      response to acute fatty acid exposure.
AB  - Preadipocytes contribute to the inflammatory responses within adipose tissue.
      Whilst fatty acids are known to elicit an inflammatory response within adipose
      tissue, the relative contribution of preadipocytes and mature adipocytes to this
      is yet to be determined. We aimed to examine the actions of common dietary fatty
      acids on the acute inflammatory and adipokine response in 3T3-L1 preadipocytes
      and differentiated mature adipocytes. Gene expression levels of key adipokines in
      3T3-L1 preadipocytes and adipocytes were determined following incubation with
      palmitic acid, myristic acid or oleic acid and positive inflammatory control,
      lipopolysaccharide for 2 and 4 h. Inflammatory kinase signalling was assessed by
      analysis of nuclear factor-kappaB, p38-mitogen-activated protein kinase and c-jun
      amino-terminal kinase phosphorylation. Under basal conditions, intracellular
      monocyte chemoattractant protein-1 and interleukin-6 gene expression levels were
      increased in preadipocytes, whereas mature adipocytes expressed increased gene
      expression levels of leptin and adiponectin. Fatty acid exposure at 2 and 4 h
      increased both monocyte chemoattractant protein-1 and interleukin-6 gene
      expression levels in preadipocytes to greater levels than in mature adipocytes.
      There was an accompanying increase of inhibitor of kappaB-alpha degradation and
      nuclear factor-kappaB (p65) (Ser536) phosphorylation with fatty acid exposure in
      the preadipocytes only. The current study points to preadipocytes rather than the
      adipocytes as the contributors to both immune cell recruitment and inflammatory
      adipokine secretion with acute increases in fatty acids. 

PMID- 24911935
TI  - Anisakis/Ascaris IgE ratio improves specificity for the diagnosis of Anisakis
      simplex sensitization in travellers and immigrants.
AB  - Anisakis simplex is a fish parasite responsible for human infection and is able
      to induce IgE-mediated reactions with several clinical manifestations. Laboratory
      diagnosis of Anisakis allergy is based on the detection of specific IgE using
      parasite whole antigen. Unfortunately, these diagnostic tools detect cross
      reactivities with other nematodes and micro-organisms leading to low specificity
      of the diagnostic tests. The aim of this retrospective study was to assess the
      diagnostic value of specific IgE to Anisakis for diagnosis of A. simplex
      sensitization in native Spanish residents (IMM, n=766) and subjects coming from
      tropical and sub-tropical geographic areas (TRO, n=233). Since Ascaris is the
      human parasite most closely related to Anisakis, specific IgE to Ascaris was also
      determined to assess Anisakis cross-reaction with other nematodes and the
      diagnostic value of Anisakis/Ascaris IgE ratio for Anisakis allergy was examined.
      IMM and TRO groups showed similar specific IgE to Anisakis levels, while TRO had
      higher levels of specific IgE to Ascaris than IMM group (p=0.001). ROC curve
      analysis determined that an Anisakis specific IgE threshold of 0.71 kU/L yielded
      93% and 82% specificities in IMM and TRO groups, respectively. A cut-off value
      >=4.4 for Anisakis/Ascaris IgE ratio increased specificity to 95% for samples
      having IgE to Ascaris >=0.35. In conclusion, the ratio of specific IgE to
      Anisakis and Ascaris improved remarkably the specificity and this parameter
      easily obtained from the commercially available system could be useful in the
      diagnosis of hypersensitivity to A. simplex.

PMID- 24911936
TI  - Contrasting associations of polymorphisms in FcgammaRIIa and DC-SIGN with the
      clinical presentation of dengue infection in a Mexican population.
AB  - Dengue virus (DENV) causes a spectrum of illness from asymptomatic infection, to
      a mild febrile illness, to occasional more severe complications including
      hemorrhage and shock. Dengue is endemic in the state of Morelos, Mexico. Two
      single nucleotide polymorphisms (SNPs), rs1801274 of FcgammaRIIa and rs4804803 of
      DC-SIGN, have been associated with protection from or susceptibility to severe
      dengue infection. Both of these polymorphisms are located in genes for receptors
      with important roles in dengue pathogenesis, and their relationship with the
      clinical presentation of dengue infection in Mexican populations is unknown. In
      this study, real-time PCR was used to characterize the distribution of rs1801274
      and rs4804803 in subjects with asymptomatic dengue infection (n=145),
      uncomplicated dengue (n=67), and severe dengue (n=36) in Morelos. In contrast
      with previous studies, the histidine (A) variant of rs1801274 was associated with
      more mild infection: carrying the histidine allele (either homozygous or
      heterozygous) was associated with protection from symptomatic infection compared
      with asymptomatic (OR 0.51, p=0.038). Histidine homozygotes were also less likely
      to present severe dengue (OR 0.34, p=0.05). Logistic regression models confirm
      this association (OR 0.48, p=0.04) and also indicate that the G allele of
      rs4804803 is associated with symptomatic dengue (OR 2.3, p=0.08), after
      accounting for other biological factors including history of infection. This
      variant was rare in this study population, with a frequency of 5.4%. These
      findings reflect the complexity of influences on the development of severe dengue
      infection. The inclusion of asymptomatic infections and adjusted case definitions
      likely do not explain the entire disparity with previous findings. Interactions
      with other polymorphisms may explain why the association of rs1801274 is reversed
      in this population compared to others. This study demonstrates the importance of
      genetic association studies in multiple genetically distinct populations. 

PMID- 24911937
TI  - Evaluation of histopathological changes, viral load and immune function of
      domestic geese infected with Newcastle disease virus.
AB  - Outbreaks of Newcastle disease in flocks of geese with high morbidity and
      mortality in southern and eastern China have been reported frequently since the
      late 1990s, which broke the traditional view that geese are considered to be the
      natural reservoir of Newcastle disease virus (NDV) but show few or no clinical
      signs after infection. In this present study, geese were infected intranasally
      with a local strain of NDV. Clinical disease and gross pathology were observed.
      Serum and immune organs were collected from geese sequentially euthanized or
      after disease-associated death. We studied the histopathology of immune organs by
      haematoxylin and eosin staining and NDV fusion protein was detected in tissues by
      immunohistochemistry. At the same time, the SYBR Green I real-time polymerase
      chain reaction assay was used to detect the viral load from the collected
      samples. Serum samples were tested for NDV-specific antibodies and avian
      influenza virus (AIV)-specific antibodies by haemagglutination inhibition (HI)
      test. The results showed that severe lesions and numerous positive reactions of
      NDV antigen were detected in the immune organs. High viral loads developed in
      immune organs of infected geese, correlating with the severity of clinical signs
      and lesions in the tissues. Furthermore, the infected geese developed low HI
      antibody titres to both AIV and NDV. The present study showed that the
      replication and dissemination of the NDV isolate was widespread in immune organs
      of geese. The study revealed that waterfowl may not only be a natural reservoir
      of NDV but also become susceptible to disease and may play a major role in the
      epidemiology of Newcastle disease. 

PMID- 24911938
TI  - Total synthesis of herbimycin A.
AB  - Benzoquinone ansamycin antibiotic herbimycin A was synthesized in 19 linear steps
      and 4.2% yield. Highlighted is the design of a chiral gamma-lactone as the C11
      C15 synthon that enabled a facile catalytic asymmetric synthesis of the
      challenging C8-C20 fragment of the target molecule. The easy access to the
      stereogenic centers and high overall yield made the strategy applicable in the
      molecular editing of benzoquinone ansamycins. 

PMID- 24911939
TI  - Compartment syndrome because of acute hemorrhagic edema of infancy: a case report
      and literature review.
AB  - Acute hemorrhagic edema of infancy (AHEI) is a benign, self-limiting vasculitis
      that usually resolves completely without any sequelae or a need for active
      therapy. To our knowledge, compartment syndrome because of AHEI has not been
      reported. Chart data for a single case were reviewed and reported in a
      retrospective study. A 19-month-old male presented with petechial rash and
      swelling of the left lower leg. AHEI was diagnosed clinically and confirmed by
      skin biopsy. On the basis of the clinical appearance, compartment syndrome of the
      foot was suspected. Measurements of compartmental pressures in the foot were well
      above the commonly cited ranges and a fasciotomy was performed. Following the
      operation, there was a marked clinical improvement in the limb perfusion. The
      child was discharged on the 20th day with marked clinical improvement; both
      active and passive leg movements were intact. We suggest that pediatric
      orthopedic surgeons should be familiar with this entity and its rare
      complication. LEVEL OF EVIDENCE: V - case report.

PMID- 24911940
TI  - Bioabsorbable pins for bone fixation in the less invasive innominate osteotomy.
AB  - For the less invasive innominate osteotomy for the treatment of developmental
      dysplasia of the hip, we aim to report radiological outcomes, complication rates
      and reoperation rates for patients whose bone grafts were secured using
      bioabsorbable pins. A retrospective study of all patients who underwent less
      invasive innominate osteotomy for persistent or delayed diagnosis developmental
      dysplasia of the hip over a period of 2 years from 2008 to 2010 was carried out.
      A total of 59 hips were identified as having had their bone graft secured with
      two bioabsorbable pins made from copolymers of L-lactic acid, D-lactic acid and
      trimethylene carbonate. The average angular correction of the acetabular index in
      the bioabsorbable group at late follow-up was 16.48 degrees  (P<0.0001). Seven
      percent of patients from the bioabsorbable pin group went on to require
      reoperation for persistent dysplasia. No patient required reoperation due to
      implant failure. There was no incidence of postoperative wound infection or other
      complication requiring medical or surgical intervention. These results
      demonstrate that the use of bioabsorbable pins to secure the bone graft is as
      effective and safe as metal fixation. 

PMID- 24911942
TI  - From nucleobases to nucleolipids: an ITC approach on the thermodynamics of their
      interactions in aqueous solutions.
AB  - Hybrid constructions based on nucleosides and lipophilic components, known as
      nucleolipids, have become an extremely interesting class of molecules, especially
      for their potential biomedical applications. In this matter, it seemed important
      to define the nature and estimate the strength of their interaction with
      polynucleotides by different ways. We report in this work a systematic
      investigation through isothermal titration calorimetry of the thermodynamics of
      the association and dissociation of adenine and thymine derivatives, not
      previously performed. Then we use the results obtained on these simple systems as
      a basis for comparison with the binding of phospholipids functionalized with
      adenosine and thymidine to polyadenylic or polyuridylic acids applying the same
      experimental technique. 

PMID- 24911941
TI  - Treatment of angiokeratoma of Mibelli alone or in combination with pulsed dye
      laser and long-pulsed Nd: YAG laser.
AB  - Treatment of angiokeratoma of Mibelli is usually challenging because of the
      location, the pathogenetic condition and the cosmetic requirements. We present
      our characteristic treatment with the application of pulsed dye laser PDL and
      lpNd:YAG laser. All of these lesions were treated by topical anesthesia with
      Emla. Combined dual PDL-lpNd:YAG (PDL: 595 nm, 5 mm/7 mm, 0.5 ms, 8-10 J/cm(2) ;
      lpNd:YAG: 3 mm/5 mm, 15 ms, 90-120 J/cm(2) ) treatment was used to treat lesions
      which with moderate to severe hyperkeratosis and hyperplasia. To the maculopapule
      ones, the energy density of lpNd:YAG might upgrade to 150 J/cm(2) . Singular PDL
      (595 nm, 5 mm/7 mm, 0.5 ms, 9-12 J/cm(2) ) treatment was used to treat lesions
      which with slight hyperkeratosis and hyperplasia. Continuous airflow cooling was
      always applied during the laser treatment. The treatment interval was 6-12 weeks.
      Of the 5 patients, 3 of them were cured and 2 of them were improved. All of them
      were satisfied with the cosmetic results. We recommended the combined dual PDL
      lpNd:YAG laser in treating severe hyperkeratotic and hyperplastic angiokeratoma
      of Mibelli. It can aid in achieving a desirable outcome whilst also reducing the
      required treatment sessions. However, most patients felt painful during the
      operation and experienced a severe long term recovery time after operation.

PMID- 24911944
TI  - Carcinoma of the fallopian tube presenting as an axillary palpable mass.

PMID- 24911943
TI  - Developmental toxicity and neurotoxicity of two matrine-type alkaloids, matrine
      and sophocarpine, in zebrafish (Danio rerio) embryos/larvae.
AB  - Matrine and sophocarpine are two major matrine-type alkaloids included in the
      traditional Chinese medicine (TCM) Kushen (the root of Sophora flavescens Ait.).
      They have been widely used clinically in China, however with few reports
      concerning their potential toxicities. This study investigated the developmental
      toxicity and neurotoxicity of matrine and sophocarpine on zebrafish
      embryos/larvae from 0 to 96/120h post fertilization (hpf). Both drugs displayed
      teratogenic and lethal effects with the EC50 and LC50 values at 145 and 240mg/L
      for matrine and 87.1 and 166mg/L for sophocarpine, respectively. Exposure of
      matrine and sophocarpine significantly altered spontaneous movement and inhibited
      swimming performance at concentrations below those causing lethality and
      malformations, indicating a neurotoxic potential of both drugs. The results are
      in agreement with most mammalian studies and clinical observations. 

PMID- 24911945
TI  - Organocatalytic enantioselective allylic alkylation of MBH carbonates with beta
      keto esters.
AB  - The highly stereoselective allylic alkylation of Morita-Baylis-Hillman carbonates
      with beta-ketoesters catalysed by beta-ICD is described. The corresponding
      products containing two adjacent quaternary and tertiary carbon centers were
      obtained in good yields with high diastereoselectivity (up to 10 : 1 dr) and
      enantioselectivity (up to 95% ee). 

PMID- 24911946
TI  - Glucose series complexity at the threshold of diabetes.
AB  - BACKGROUND: One of the earliest signs of dysfunction in a complex system is the
      simplification of its output. A well-accepted method to measure this phenomenon
      is detrended fluctuation analysis (DFA). Herein, we evaluated the usefulness of
      DFA at the threshold of type 2 diabetes mellitus (T2DM). METHODS: We report on
      the clinical and glucometric characteristics of a sample of 103 patients at
      increased risk of developing T2DM. All patients had HbA1c levels 5%-6.4% and met
      at least one of the following criteria: body mass index (BMI) > 30 kg/m2,
      essential hypertension or a first-degree relative with T2DM. For each patient, a
      24-h glucose time series was obtained, and the clinical and glucometric variables
      were compared. RESULTS: There was a significant correlation between the number of
      National Cholesterol Education Program--Adult Treatment Panel (ATP III) metabolic
      syndrome (MS)-defining criteria and DFA (rho = 0.231, P = 0.019), and DFA
      differed significantly between patients meeting or not the ATP III definition of
      MS (1.443 vs. 1.399, respectively; P = 0.018). The DFA was not correlated with
      HbA1c. Depending on how it was calculated, the area under the log(Fn)~log(n)
      curve correlated with HbA1c levels or the number of MS criteria. Conventional
      variability metrics (mean amplitude of glycemic excursions) did not differ
      between patients complying or not with the definition of MS. CONCLUSIONS:
      Complexity analysis is capable of detecting differences in variables related to
      the risk of developing T2DM and could be a useful tool to study the initial
      phases of glucoregulatory dysfunction leading to T2DM.

PMID- 24911947
TI  - Non-thermal plasma treatment diminishes fungal viability and up-regulates
      resistance genes in a plant host.
AB  - Reactive oxygen and nitrogen species can have either harmful or beneficial
      effects on biological systems depending on the dose administered and the species
      of organism exposed, suggesting that application of reactive species can possibly
      produce contradictory effects in disease control, pathogen inactivation and
      activation of host resistance. A novel technology known as atmospheric-pressure
      non-thermal plasma represents a means of generating various reactive species that
      adversely affect pathogens (inactivation) while simultaneously up-regulating host
      defense genes. The anti-microbial efficacy of this technology was tested on the
      plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible
      host plant species Solanum lycopercicum. Germination of fungal spores suspended
      in saline was decreased over time after exposed to argon (Ar) plasma for 10 min.
      Although the majority of treated spores exhibited necrotic death, apoptosis was
      also observed along with the up-regulation of apoptosis related genes. Increases
      in the levels of peroxynitrite and nitrite in saline following plasma treatment
      may have been responsible for the observed spore death. In addition, increased
      transcription of pathogenesis related (PR) genes was observed in the roots of the
      susceptible tomato cultivar (S. lycopercicum) after exposure to the same Ar
      plasma dose used in fungal inactivation. These data suggest that atmospheric
      pressure non-thermal plasma can be efficiently used to control plant fungal
      diseases by inactivating fungal pathogens and up-regulating mechanisms of host
      resistance. 

PMID- 24911948
TI  - Costs of autism spectrum disorders in the United Kingdom and the United States.
AB  - IMPORTANCE: The economic effect of autism spectrum disorders (ASDs) on
      individuals with the disorder, their families, and society as a whole is poorly
      understood and has not been updated in light of recent findings. OBJECTIVE: To
      update estimates of age-specific, direct, indirect, and lifetime societal
      economic costs, including new findings on indirect costs, such as individual and
      parental productivity costs, associated with ASDs. DESIGN, SETTING, AND
      PARTICIPANTS: A literature review was conducted of US and UK studies on
      individuals with ASDs and their families in October 2013 using the following
      keywords: age, autism spectrum disorder, prevalence, accommodation, special
      education, productivity loss, employment, costs, and economics. Current data on
      prevalence, level of functioning, and place of residence were combined with mean
      annual costs of services and support, opportunity costs, and productivity losses
      of individuals with ASDs with or without intellectual disability. EXPOSURE:
      Presence of ASDs. MAIN OUTCOMES AND MEASURES: Mean annual medical, nonmedical,
      and indirect economic costs and lifetime costs were measured for individuals with
      ASDs separately for individuals with and without intellectual disability in the
      United States and the United Kingdom. RESULTS: The cost of supporting an
      individual with an ASD and intellectual disability during his or her lifespan was
      $2.4 million in the United States and L1.5 million (US $2.2 million) in the
      United Kingdom. The cost of supporting an individual with an ASD without
      intellectual disability was $1.4 million in the United States and L0.92 million
      (US $1.4 million) in the United Kingdom. The largest cost components for children
      were special education services and parental productivity loss. During adulthood,
      residential care or supportive living accommodation and individual productivity
      loss contributed the highest costs. Medical costs were much higher for adults
      than for children. CONCLUSIONS AND RELEVANCE: The substantial direct and indirect
      economic effect of ASDs emphasizes the need to continue to search for effective
      interventions that make best use of scarce societal resources. The distribution
      of economic effect across many different service systems raises questions about
      coordination of services and sectors. The enormous effect on families also
      warrants policy attention.

PMID- 24911949
TI  - Optically controllable dual-gate organic transistor produced via phase separation
      between polymer semiconductor and photochromic spiropyran molecules.
AB  - We produced an optically controllable dual-gate organic field-effect transistor
      by a simple one-step spin-coating of a mixed solution of photochromic spiropyran
      (SP) and poly(3-hexylthiophene) (P3HT). Postannealing enhanced polymer chain
      ordering of P3HT to induce phase separation into an SP-rich lower layer and an SP
      free upper layer. These layers worked independently as transistor channels with
      distinct optical responsivity. The top channel was optically inactive, but the
      bottom channel was optically active, because of the photoisomerization of SP.
      These results demonstrate the potential of our technique to produce a
      multifunctional photoactive organic transistor by a simple process. 

PMID- 24911950
TI  - Linear optical and electronic properties of the polar metallic ruthenate
      (Sr,Ca)Ru2O6.
AB  - Using first-principles calculations, we compute the linear optical properties for
      cation ordered (Sr,Ca)Ru2O6. Our calculations show that this polar ferromagnetic
      metallic oxide exhibits optical anisotropy along the principal directions of the
      optical indicatrix owing to the absence of inversion symmetry in the crystal
      structure. The calculated reflectivity is used to locate the onset of the inter
      band transitions at an energy of 1.3 eV. Comparing the optical conductivity with
      the electronic band structure, we identify the possible optical transitions.
      Finally, we apply the generalized Drude model to deduce an enhancement of the
      effective mass, m(*) ~ 4.9m(e), in ordered (Sr,Ca)Ru2O6. Moreover, we show that
      removal of the polar distortions decrease the effective mass to m(*) ~ 4.4m(e),
      suggesting that control over the amplitude of the polar displacements could be
      used to tune the degree of electronic correlation in oxide conductors without
      inversion symmetry.

PMID- 24911951
TI  - Astrocytes of the murine model for Down Syndrome Ts65Dn display reduced
      intracellular ionic zinc.
AB  - Zinc is an essential trace element that is critical for a large number of
      structural proteins, enzymatic processes and transcription factors. In the brain,
      zinc ions are involved in synaptic transmission. The homeostasis of zinc is
      crucial for cell survival and function, and cells have developed a wide variety
      of systems to control zinc concentration. Alterations in free zinc concentration
      have been related with brain dysfunction. Down Syndrome individuals present
      alterations in free zinc concentration and in some of the proteins related with
      zinc homeostasis. We have analyzed the amount of free zinc and the zinc chelating
      protein metallothionein 3 in the astrocytes using primary cultures of the murine
      model Ts65Dn. We have observed a higher number of zinc positive spots in the
      cytoplasm of trisomic astrocytes but a decrease in the total concentration of
      total intracellular free zinc concentration (including the spots) respect to
      control astrocytes. Using FM1-43 staining, we found that the endocytic function
      remains unaltered. Therefore, a possible explanation for this lower concentration
      of free zinc could be the higher concentration of metallothionein 3 present in
      the cytoplasm of trisomic astrocytes. The blockade of metallothionein 3
      expression using an specific siRNA induced an increase in the concentration of
      free zinc in basal conditions but failed to increase the uptake of zinc after
      incubation with zinc ions. 

PMID- 24911952
TI  - Possible involvement of VEGF signaling system in rescuing effect of endogenous
      acetylcholine on NMDA-induced long-lasting hippocampal cell damage in organotypic
      hippocampal slice cultures.
AB  - In our previous study, elevation of endogenous acetylcholine (ACh) by tacrine
      (THA) rescued NMDA-induced long-lasting hippocampal cell damage via muscarinic M1
      receptors. However, the detailed molecular mechanism underlying the effect of ACh
      is unclear. This study investigated possible involvement of the VEGF signaling
      system in the rescuing effect of ACh on N-methyl-d-aspartate (NMDA)-induced long
      lasting hippocampal cell damage using organotypic hippocampal slice cultures
      (OHSCs). As previously reported, NMDA pretreatment caused long-lasting
      hippocampal cell damage in OHSCs in a manner reversible by treatment with THA.
      The protein kinase C (PKC) inhibitor Ro31-8220, but not the extracellular signal
      regulated kinase (ERK) inhibitor U0126, dose-dependently and almost completely
      abolished the effect of THA. The rescuing effect of THA was also partially but
      significantly blocked by Ki8751, a selective inhibitor of type 2 vascular
      endothelial growth factor (VEGF) receptor (VEGFR-2) tyrosine kinase. NMDA
      pretreatment elevated the expression level of HIF1alpha, whereas it decreased the
      expression of VEGF-A. Moreover, NMDA pretreatment reduced the level of
      phosphorylated VEGFR-2 without apparently affecting the level of VEGFR-2 or beta
      actin. These NMDA pretreatment-induced changes were significantly attenuated by
      THA treatment. Immunohistochemical analysis conducted 6days after NMDA
      pretreatment revealed that VEGF-A and VEGFR-2 were mainly expressed on astrocytes
      and neurons, respectively, in OHSCs. In OHSCs pretreated with NMDA, THA treatment
      induced a morphological and activation-related change in astrocytes expressing
      VEGF-A. The present results demonstrate that endogenous acetylcholine plays a
      rescuing role towards excitotoxicity-induced long-lasting hippocampal cell damage
      in part via paracrine VEGF signaling between astrocytes and hippocampal neurons
      or autocrine VEGF signaling in hippocampal neurons in OHSCs. 

PMID- 24911953
TI  - Protein kinases paralleling late-phase LTP formation in dorsal hippocampus in the
      rat.
AB  - Hippocampal long term potentiation (LTP), representing a cellular model for
      learning and memory formation, can be dissociated into at least two phases: a
      protein-synthesis-independent early phase, lasting about 4h and a protein
      synthesis-dependent late phase LTP lasting 6h or longer, or even days. A large
      series of protein kinases have been shown to be involved and herein, a distinct
      set of protein kinases proposed to be involved in memory retrieval in previous
      work was tested in dorsal hippocampus of the rat following induction of late
      phase LTP. A bipolar stimulation electrode was chronically implanted into the
      perforant path, while two monopolar recording electrodes were implanted into the
      dentate gyrus of the dorsal hippocampus. The recording electrode was measuring
      extracellular excitatory postsynaptic potentials, while the other one measured
      population spikes. Protein kinases were determined by immunoblotting and
      immunoflourescence on hippocampal areas showed the distribution pattern of
      protein kinases PKN1 and NEK7. Induction of LTP was proven, elevated levels for
      protein kinases PKN1, RPS6KB1, STK4, CDC42BPB, PRKG, TLK, BMX and decreased
      levels for NEK7, MAK14 and PLK1 were observed. A remarkable overlap of protein
      kinases observed in spatial memory processes with those proposed in LTP formation
      was demonstrated. The findings may be relevant for design of future studies on
      protein kinases and for the interpretation of previous work. 

PMID- 24911954
TI  - Cocaine-induced neuroadaptations in the dorsal striatum: glutamate dynamics and
      behavioral sensitization.
AB  - Recent evidence suggests that diminished ability to control cocaine seeking
      arises from perturbations in glutamate homeostasis in the nucleus accumbens.
      However, the neurochemical substrates underlying cocaine-induced neuroadaptations
      in the dorsal striatum and how these mechanisms link to behavioral plasticity is
      not clear. We employed glutamate-sensitive microelectrodes and amperometry to
      study the impact of repeated cocaine administration on glutamate dynamics in the
      dorsolateral striatum of awake freely-moving rats. Depolarization-evoked
      glutamate release was robustly increased in cocaine-pretreated rats challenged
      with cocaine. Moreover, the clearance of glutamate signals elicited either by
      terminal depolarization or blockade of non-neuronal glutamate transporters slowed
      down dramatically in cocaine-sensitized rats. Repeated cocaine exposure also
      reduced the neuronal tone of striatal glutamate. Ceftriaxone, a beta-lactam
      antibiotic that activates the astrocytic glutamate transporter, attenuated the
      effects of repeated cocaine exposure on synaptic glutamate release and glutamate
      clearance kinetics. Finally, the antagonism of AMPA glutamate receptors in the
      dorsolateral striatum blocked the development of behavioral sensitization to
      repeated cocaine administration. Collectively, these data suggest that repeated
      cocaine exposure disrupts presynaptic glutamate transmission and transporter
      mediated clearance mechanisms in the dorsal striatum. Moreover, such alterations
      produce an over activation of AMPA receptors in this brain region leading to the
      sensitized behavioral response to repeated cocaine. 

PMID- 24911955
TI  - Differential self-assembly and tunable emission of aromatic peptide bola
      amphiphiles containing perylene bisimide in polar solvents including water.
AB  - We demonstrate the self-assembly of bola-amphiphile-type conjugates of dipeptides
      and perylene bisimide (PBI) in water and other polar solvents. Depending on the
      nature of the peptide used (glycine-tyrosine, GY, or glycine-aspartic acid, GD),
      the balance between H-bonding and aromatic stacking can be tailored. In aqueous
      buffer, PBI-[GY]2 forms chiral nanofibers, resulting in the formation of a
      hydrogel, while for PBI-[GD]2 achiral spherical aggregates are formed,
      demonstrating that the peptide sequence has a profound effect on the structure
      formed. In water and a range of other polar solvents, self-assembly of these two
      PBI-peptides conjugates results in different nanostructures with highly tunable
      fluorescence performance depending on the peptide sequence employed, e.g.,
      fluorescent emission and quantum yield. Organogels are formed for the PBI-[GD]2
      derivative in DMF and DMSO while PBI-[GY]2 gels in DMF. To the best of our
      knowledge, this is the first successful strategy for using short peptides,
      specifically, their sequence/structure relationships, to manipulate the PBI
      nanostructure and consequent optical properties. The combination of controlled
      self-assembly, varied optical properties, and formation of aqueous and organic
      gel-phase materials may facilitate the design of devices for various applications
      related to light harvesting and sensing. 

PMID- 24911956
TI  - Bone Marrow Stromal Cells Combined With a Honeycomb Collagen Sponge Facilitate
      Neurite Elongation In Vitro and Neural Restoration in the Hemisected Rat Spinal
      Cord.
AB  - In the last decade, researchers and clinicians have reported that transplantation
      of bone marrow stromal cells (BMSCs) promotes functional recovery after brain or
      spinal cord injury (SCI). However, an appropriate scaffold designed for the
      injured spinal cord is needed to enhance the survival of transplanted BMSCs and
      to promote nerve regeneration. We previously tested a honeycomb collagen sponge
      (HC), which when applied to the transected spinal cord allowed bridging of the
      gap with nerve fibers. In this study, we examined whether the HC implant combined
      with rat BMSCs increases nerve regeneration in vitro and enhances functional
      recovery in vivo. We first evaluated the neurite outgrowth of rat dorsal root
      ganglion (DRG) explants cultured on HC with or without BMSCs in vitro.
      Regeneration of neurites from the DRGs was increased by BMSCs combined with HC
      scaffolds. In the in vivo study, 3-mm-long HC scaffolds with or without BMSCs
      were implanted into the hemisected rat thoracic spinal cord. Four weeks after the
      procedure, rats implanted with HC scaffolds containing BMSCs displayed better
      motor and sensory recovery than those implanted with HC scaffolds only.
      Histologically, more CGRP-positive sensory fibers at the implanted site and 5-HT
      positive serotonergic fibers contralateral to the implanted site were observed in
      spinal cords receiving BMSCs. Furthermore, more rubrospinal neurons projected
      distally to the HC implant containing BMSCs. Our study indicates that the
      application of BMSCs in a HC scaffold in the injured spinal cord directly
      promoted sensory nerve and rubrospinal tract regeneration, thus resulting in
      functional recovery. 

PMID- 24911958
TI  - Effects of prey macronutrient content on body composition and nutrient intake in
      a web-building spider.
AB  - The nutritional composition of diets can vary widely in nature and have large
      effects on the growth, reproduction and survival of animals. Many animals,
      especially herbivores, will tightly regulate the nutritional composition of their
      body, which has been referred to as nutritional homeostasis. We tested how
      experimental manipulation of the lipid and protein content of live prey affected
      the nutrient reserves and subsequent diet regulation of web-building spiders,
      Argiope keyserlingi. Live locusts were injected with experimental solutions
      containing specific amounts of lipid and protein and then fed to spiders. The
      nutrient composition of the spiders' bodies was directly related to the nutrient
      composition of the prey on which they fed. We then conducted an experiment where
      spiders were fed either high lipid or high protein prey and subsequently provided
      with two large unmanipulated locusts. Prior diet did not affect the amount or
      ratio of lipid and protein ingested by spiders when feeding on unmanipulated
      prey. Argiope keyserlingi were flexible in the storage of lipid and protein in
      their bodies and did not bias their extraction of nutrients from prey to
      compensate for previously biased diets. Some carnivores, especially those that
      experience frequent food limitation, may be less likely to strictly regulate
      their body composition than herbivores because food limitation may encourage
      opportunistic ingestion and assimilation of nutrients. 

PMID- 24911957
TI  - Online dietary intake estimation: the Food4Me food frequency questionnaire.
AB  - BACKGROUND: Dietary assessment methods are important tools for nutrition
      research. Online dietary assessment tools have the potential to become invaluable
      methods of assessing dietary intake because, compared with traditional methods,
      they have many advantages including the automatic storage of input data and the
      immediate generation of nutritional outputs. OBJECTIVE: The aim of this study was
      to develop an online food frequency questionnaire (FFQ) for dietary data
      collection in the "Food4Me" study and to compare this with the validated European
      Prospective Investigation of Cancer (EPIC) Norfolk printed FFQ. METHODS: The
      Food4Me FFQ used in this analysis was developed to consist of 157 food items.
      Standardized color photographs were incorporated in the development of the
      Food4Me FFQ to facilitate accurate quantification of the portion size of each
      food item. Participants were recruited in two centers (Dublin, Ireland and
      Reading, United Kingdom) and each received the online Food4Me FFQ and the printed
      EPIC-Norfolk FFQ in random order. Participants completed the Food4Me FFQ online
      and, for most food items, participants were requested to choose their usual
      serving size among seven possibilities from a range of portion size pictures. The
      level of agreement between the two methods was evaluated for both nutrient and
      food group intakes using the Bland and Altman method and classification into
      quartiles of daily intake. Correlations were calculated for nutrient and food
      group intakes. RESULTS: A total of 113 participants were recruited with a mean
      age of 30 (SD 10) years (40.7% male, 46/113; 59.3%, 67/113 female). Cross
      classification into exact plus adjacent quartiles ranged from 77% to 97% at the
      nutrient level and 77% to 99% at the food group level. Agreement at the nutrient
      level was highest for alcohol (97%) and lowest for percent energy from
      polyunsaturated fatty acids (77%). Crude unadjusted correlations for nutrients
      ranged between .43 and .86. Agreement at the food group level was highest for
      "other fruits" (eg, apples, pears, oranges) and lowest for "cakes, pastries, and
      buns". For food groups, correlations ranged between .41 and .90. CONCLUSIONS: The
      results demonstrate that the online Food4Me FFQ has good agreement with the
      validated printed EPIC-Norfolk FFQ for assessing both nutrient and food group
      intakes, rendering it a useful tool for ranking individuals based on nutrient and
      food group intakes.

PMID- 24911959
TI  - Copper (Cu)-silica nanocomposite containing valence-engineered Cu: a new strategy
      for improving the antimicrobial efficacy of Cu biocides.
AB  - Copper (Cu) compounds are widely used as antibacterial/antifungal agents for
      protecting food crops. Prolonged use of Cu biocides would lead to undesirable Cu
      levels in agricultural soil. In the absence of a suitable alternative, prudent
      use of Cu biocides is required. This paper reports for the first time a composite
      material of sol-gel silica host matrix loaded with mixed-valence Cu as an
      alternative to conventional biocides. In this composite material, Cu is present
      in different oxidation states. The hydrophilic silica matrix serves as a water
      dispersible delivery vehicle for antimicrobial Cu. It is hypothesized that a
      mixed-valence Cu system, specifically enriched with Cu(0) and Cu(I), will exhibit
      enhanced antimicrobial efficacy over traditional Cu(II) compounds. Materials were
      characterized by high-resolution transmission electron microscopy and X-ray
      photoelectron spectroscopy for the determination of particle size, morphology,
      crystallinity, and Cu oxidation states. Antimicrobial studies against Xanthomonas
      alfalfae and Escherichia coli (minimum inhibitory concentration) showed improved
      efficacy in MV-CuSiNG treatment compared to CuSiNG and other controls.
      Phytotoxicity studies performed (in Vinca sp. and Hamlin orange) under greenhouse
      conditions showed that the newly prepared nanocomposite is safe for plants,
      demonstrating potential usefulness of the material in agricultural biocides. 

PMID- 24911960
TI  - Exposing the role of electron correlation in strong-field double ionization: X
      ray transient absorption of orbital alignment in Xe+ and Xe2+.
AB  - Orbital alignment measurements and theory are used to examine the role of
      electron correlation during atomic strong-field double ionization (795 nm, (1-5)
      * 10(14) W cm(-2)). High-order harmonic, transient absorption spectroscopy is
      used to measure the angular distributions of singly and doubly tunnel-ionized
      xenon atomic states via 4d core to 5p valence shell transitions between 55 and 60
      eV. The experimental MJ alignment distributions are compared to results of a rate
      equation model based on sequential ionization, previously developed for coherent
      electron motion, and now applied to account for the alignment prepared by
      tunneling ionization. The hole generated in the (2)P3/2 state of Xe(+) is
      measured to be entirely composed of |MJ| = 1/2, in agreement with theory. The
      result is a higher degree of alignment than previously reported. Because the
      model neglects effects of electron-ion recollision, the theory predicts a high
      degree of alignment in both spin-parallel (triplet) and antiparallel (singlet)
      terms of Xe(2+). However, the alignment generated with linearly polarized light
      is observed to be spin-state dependent. The measured alignments for triplet spin
      states ((3)P2 has |MJ| = [0 : 1 : 2] of [27+/-6 : 45+/-11 : 29+/-0] and (3)P1 has
      |MJ| = [0 : 1] of [56+/-2 : 44+/-2]) are in good agreement with the expectations
      of theory, which are [33 : 53 : 14] and [66 : 33], respectively. The results
      validate the rate equation model for sequential tunnel ionization. However, the
      alignment extracted for a singlet state is greatly diminished: (1)D2 is measured
      to be [18+/-1 : 39+/-2 : 43 +/- 2] compared to theoretical expectation of [60 :
      39 : 1] for |MJ| = [0 : 1 : 2]. The poor agreement with the sequential ionization
      model suggests that the alignment of (1)D2 is strongly influenced by the high
      propensity for the liberated first electron to return to and recollide with its
      parent atomic orbital. Therefore, although the influence of electron recollision
      appears minor in the triplet states and suggests sequential ionization, electron
      correlation between the ionic core and the first ionized electron cannot be
      ignored in the singlet state. Singlet states are likely to be generated through
      nonsequential double ionization over the intensity range where the experiments
      are performed. 

PMID- 24911963
TI  - DOSY-NMR and raman investigations on the self-aggregation and cyclodextrin
      complexation of vanillin.
AB  - Vanillin (4-hydroxy-3-methoxybenzaldehyde) is a phenolic aldehyde with limited
      solubility in water; in this work, we investigate its self-aggregation, as well
      as its complexation equilibria with beta-cyclodextrin by using nuclear magnetic
      resonance (NMR) and vibrational spectroscopy. In particular, diffusion-ordered
      NMR (DOSY) measurements allowing to detect diffusional changes caused by
      aggregation/inclusion phenomena lead to a reliable estimate of the equilibrium
      constants of these processes, while Raman spectroscopy was used to further
      characterize some structural details of vanillin self-aggregates and inclusion
      complexes. Although the self-association binding constant of vanillin in water
      was found to be low (K(a) ~10), dimeric species are not negligible within the
      investigated range of concentration (3-65 mM); on the other hand, formation of
      beta-cyclodextrin self-aggregates was not detected by DOSY measurements on
      aqueous solutions of beta-cyclodextrin at different concentrations (2-12 mM).
      Finally, the binding of vanillin with beta-cyclodextrin, as measured by the DOSY
      technique within a narrow range of concentrations (2-15 mM) by assuming the
      existence of only the monomeric 1:1 vanillin/beta-CD complex, was about an order
      of magnitude higher (K(c) ~ 90) than self-aggregation. However, the value of the
      equilibrium constant for this complexation was found to be significantly affected
      by the analytical concentrations of the host and guest system, thus indicating
      that K(c) is an "apparent" equilibrium constant.

PMID- 24911964
TI  - Effects of oral lycopene supplementation on vascular function in patients with
      cardiovascular disease and healthy volunteers: a randomised controlled trial.
AB  - AIMS: The mechanisms by which a 'Mediterranean diet' reduces cardiovascular
      disease (CVD) burden remain poorly understood. Lycopene is a potent antioxidant
      found in such diets with evidence suggesting beneficial effects. We wished to
      investigate the effects of lycopene on the vasculature in CVD patients and
      separately, in healthy volunteers (HV). METHODS AND RESULTS: We randomised 36
      statin treated CVD patients and 36 healthy volunteers in a 2?1 treatment
      allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a
      double-blind trial. Forearm responses to intra-arterial infusions of
      acetylcholine (endothelium-dependent vasodilatation; EDV), sodium nitroprusside
      (endothelium-independent vasodilatation; EIDV), and NG-monomethyl-L-arginine
      (basal nitric oxide (NO) synthase activity) were measured using venous
      plethysmography. A range of vascular and biochemical secondary endpoints were
      also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to
      +93%, P = 0.03 vs. placebo) without changes to EIDV, or basal NO responses. HVs
      did not show changes in EDV after lycopene treatment. Blood pressure, arterial
      stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo
      treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients
      had impaired EDV compared with HV (30% lower; 95% CI: -45% to -10%, P = 0.008),
      despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: -1.6 to -0.9 mmol/L,
      P<0.001). Post-therapy EDV responses for lycopene-treated CVD patients were
      similar to HVs at baseline (2% lower, 95% CI: -30% to +30%, P = 0.85), also
      suggesting lycopene improved endothelial function. CONCLUSIONS: Lycopene
      supplementation improves endothelial function in CVD patients on optimal
      secondary prevention, but not in HVs. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01100385.

PMID- 24911965
TI  - Risk factors for development of chronic kidney disease following renal
      infarction: retrospective evaluation of emergency room patients from a single
      center.
AB  - BACKGROUND: Previous studies have analyzed factors associated with renal
      infarction so that patients can be provided with earlier diagnosis and treatment.
      However, the factors associated with development of chronic kidney disease (CKD)
      following renal infarction are unknown. METHODS: We retrospectively reviewed the
      records of patients with a diagnosis of renal infarction based on enhanced
      computed tomography. All patients were admitted to a single emergency department
      in Taiwan from 1999 to 2008. Univariate and multivariate analysis were used to
      assess the effect of different factors on development of CKD based on estimates
      of the glomerular filtration rate (eGFR) at admission and at 3-12 months after
      discharge. RESULTS: Univariate analysis indicated significantly increased risk of
      CKD in patients older than 50 years, with symptoms for 24 h or less before
      admission, lower eGFR at admission, APACHE II score greater than 7, SOFA score
      greater than 1, ASA score greater than 2, and SAPS II score greater than 15.
      Multivariate analysis indicated that only SOFA score greater than 1 was
      significantly and independently associated with CKD at follow-up (p<0.001).
      CONCLUSIONS: A total of 32.5% of patients admitted for renal infarction over a
      ten-year period developed CKD at 3-12 months after discharge. A SOFA score
      greater than 1 was significantly and independently associated with development of
      CKD in these patients.

PMID- 24911967
TI  - Multiple and antagonistic effects of water on intrinsic physical properties of
      model Fischer-Tropsch cobalt catalysts evidenced by in situ X-ray diffraction.
AB  - Direct evidence for cobalt oxidation under water treatment at 230  degrees C was
      revealed using in situ XRD, even in the presence of small amounts of H2.
      Oxidation kinetics was proved to be particle size dependent. The resulting Co3O4
      showed a firmly smaller coherent domain size than the initial calcined catalyst. 

PMID- 24911966
TI  - Neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio as an
      early predictor of moderate/severe ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a state of exaggerated inflammatory
      response during controlled ovarian hyperstimulation (COH). Neutrophil:lymphocyte
      ratio (NLR) and platelet:lymphocyte ratio (PLR) are known to reflect systemic
      inflammation. The aim of this study was to investigate whether these inflammatory
      markers could be used as reliable markers in the early prediction of moderate-to
      severe OHSS. The study group consisted of 54 patients who developed moderate-to
      severe OHSS and the control group was 54 patients who did not develop OHSS
      undergoing IVF/ICSI. NLR and PLR were calculated from complete blood counts
      before the COH. NLR and PLR were significantly elevated in the OHSS group
      compared with the controls (3.2 +/- 0.9 and 182.9 +/- 49.8 vs 1.8 +/- 0.5 and
      160.6 +/- 48.5, respectively) (p < 0.05, for all). However, only NLR had positive
      associations between OHSS risk factors (p < 0.05, for all). NLR was superior to
      PLR as an early predictor of OHSS with an area under the ROC curve of 0.91
      (sensitivity = 85% and specificity = 78%). In conclusion, we found that NLR can
      be used as an early marker of OHSS.

PMID- 24911968
TI  - Bismuth induced enhanced green emission from terbium ions and their complex in
      thin films.
AB  - Bismuth nanoparticles (NPs) have been prepared by the pulsed laser ablation
      technique using the third harmonics of a Nd-YAG laser. UV-absorption and TEM
      micrographs show Bi NPs of spherical shape with the average particle size ranging
      from 15 to 20 nm. These NPs were dispersed with Tb(3+) ions and their complex
      with salicylic acid (Sal) in polyvinyl alcohol to obtain thin films. The
      influence of Bi NPs on the emissive properties of Tb(3+) ions and the
      [Tb(Sal)3(phen)] complex has been studied by luminescence spectroscopy using 266
      nm and 355 nm as excitation wavelengths. The luminescence intensity of Tb(3+)
      ions complexed with Sal in the thin polymer films increased significantly as
      compared to the Tb(3+) ions in the presence of Bi NPs on excitation at 355 nm.
      However, terbium ions in the case of the [Tb(Sal)3(phen)] complex together with
      NPs show an intense and extended emission spectrum in the 375-700 nm range for
      transitions arising from (5)D3 and (5)D4 levels to different (7)F(J) levels on
      266 nm excitation. The luminescence enhancement has also been supported by
      lifetime measurements.

PMID- 24911969
TI  - Piezo2 channel conductance and localization domains in Merkel cells of rat
      whisker hair follicles.
AB  - We have recently shown that Merkel cells transduce tactile stimuli via Piezo2
      channels to initiate the sense of touch. Here we performed patch-clamp recordings
      to assess single channel activity on the membranes of Merkel cells in whisker
      hair follicles. Under the cell-attached configuration, most Merkel cell membrane
      patches showed large outward unitary currents with single channel conductance
      being ~200pS. The outward unitary currents were not affected by negative
      pressures up to 150mmHg when applied to the membrane patches. The application of
      negative pressures up to 190mmHg also could not directly elicit any inward
      unitary current in the membrane patches. However, after establishing the whole
      cell configuration, mechanically activated currents (MA) that resembled Piezo2
      currents could be elicited by membrane displacements in every Merkel cell tested.
      While the MA current decayed rapidly, a small steady-state current component with
      significant channel noise could be observed. Applications of stationary and non
      stationary fluctuation analyses to the MA currents yielded single channel
      conductance of 32.5+/-3.8 and 54.0+/-5.3pS, respectively. The lack of mechanical
      responses under the cell-attached configuration and the existence of Piezo2 MA
      currents under the whole-cell configuration raised a possibility that Piezo2
      channels are preferentially located on Merkel cell processes, the membrane
      domains inaccessible by recording electrodes. 

PMID- 24911970
TI  - Resveratrol increases anti-aging Klotho gene expression via the activating
      transcription factor 3/c-Jun complex-mediated signaling pathway.
AB  - The Klotho gene functions as an aging suppressor gene. Evidence from animal
      models suggests that induction of Klotho expression may be a potential treatment
      for age-associated diseases. However, the molecular mechanism involved in
      regulating renal Klotho gene expression remains unclear. In this study, we
      determined that resveratrol, a natural polyphenol, induced renal Klotho
      expression both in vivo and in vitro. In the mouse kidney, resveratrol
      administration markedly increased both Klotho mRNA and protein expression. In
      resveratrol-treated NRK-52E cells, increased Klotho expression was accompanied by
      the upregulation and nuclear translocation of activating transcription factor 3
      (ATF3) and c-Jun. ATF3 or c-Jun overexpression enhanced the transcriptional
      activation of Klotho. Conversely, resveratrol-induced Klotho expression was
      attenuated in the presence of dominant-negative ATF3 or c-Jun.
      Coimmunoprecipitation and a chromatin immunoprecipitation assay revealed that
      ATF3 physically interacted with c-Jun and that the ATF3/c-Jun complex directly
      bound to the Klotho promoter through ATF3- and AP-1-binding elements. c-Jun
      cotransfection augmented the effects of ATF3 on Klotho transcription in vitro.
      Although Sirtuin 1 mRNA expression was induced by resveratrol and involved in
      regulating Klotho mRNA expression, it was not the primary cause for the
      aforementioned ATF3/c-Jun pathway. In summary, resveratrol enhances the renal
      expression of the anti-aging Klotho gene, and the transcriptional factors ATF3
      and c-Jun functionally interact and coordinately regulate the resveratrol
      mediated transcriptional activation of Klotho. 

PMID- 24911971
TI  - The relative influence of neighbourhood incivilities, cognitive social capital,
      club membership and individual characteristics on positive mental health.
AB  - Previous research indicates that residents' perceptions of their neighbourhoods
      can have an adverse influence on their health and wellbeing over and above the
      influence of structural disadvantage. Contrary to most prior research, this study
      employed an indicator of positive wellbeing and assessed the impact of individual
      characteristics, perceived social and environmental incivilities, indicators of
      cognitive and structural social capital, and perceived safety. Analyses of data
      from a large regional UK representative study (n=8237; 69.64% response rate)
      found the most influential determinants of wellbeing were physical health
      problems, age, SES and cognitive social capital. Smaller, significant effects
      were also found for environmental and social incivilities, and for perceived
      safety. The effect of cognitive social capital was moderated by age, with a
      stronger effect found among those aged 65 years and over than among younger
      participants. Findings indicate that the promotion of positive mental health
      within communities may be facilitated by efforts to foster a greater sense of
      belonging among residents, and that older adults may benefit most from such
      efforts. 

PMID- 24911972
TI  - Update on hepatitis C virus resistance to direct-acting antiviral agents.
AB  - Resistance to direct-acting antiviral (DAA) agents against hepatitis C virus
      (HCV) infection is driven by the selection of mutations at different positions in
      the NS3 protease, NS5B polymerase and NS5A proteins. With the exception of NS5B
      nucleos(t)ide inhibitors, most DAAs possess a low genetic barrier to resistance,
      with significant cross-resistance between compounds belonging to the same family.
      However, a specific mutation profile is associated with each agent or drug class
      and varies depending on the genotype/subtype (e.g., genotype 1b showed higher
      rates of sustained virological response (SVR) and a higher genetic barrier for
      resistance than genotype 1a). Moreover, some resistance mutations exist as
      natural polymorphisms in certain genotypes/subtypes at frequencies that require
      baseline drug resistance testing before recommending certain antivirals. For
      example, the polymorphism Q80K is frequently found among genotype 1a (19-48%) and
      is associated with resistance to simeprevir. Similarly, L31M and Y93H, key
      resistance mutations to NS5A inhibitors, are frequently found (6-12%) among NS5A
      genotype 1 sequences. In particular, the presence of these polymorphisms may be
      of relevance in poorly interferon-responsive patients (i.e., null responders and
      non-CC IL28B) under DAA-based therapies in combination with pegylated interferon
      alpha plus ribavirin. The relevance of pre-existing resistance mutations for
      responses to interferon-free DAA therapies is unclear for most regimens and
      requires further study. 

PMID- 24911973
TI  - Comparative assessment of the reproductive status of female Atlantic bluefin tuna
      from the Gulf of Mexico and the Mediterranean Sea.
AB  - Despite attention focused on the population status and rebuilding trajectory of
      Atlantic bluefin tuna (Thunnus thynnus), the reproduction and spawning biology
      remains poorly understood, especially in the NW Atlantic. At present, the eastern
      and western spawning populations are believed to exhibit different reproductive
      characteristics and, consequently, stock productivity. However, our study
      suggests that the two spawning populations, the Gulf of Mexico and the
      Mediterranean Sea, could show similar reproductive features and spawning
      strategies. Between 2007 and 2009, gonad samples from female Atlantic bluefin
      tuna were collected in the northern Gulf of Mexico (n = 147) and in the western
      Mediterranean Sea (n = 40). The histological and stereological analysis confirmed
      that sampled eastern and western bluefin tuna exhibit the same spawning duration
      (three months) but the spawning in the Gulf of Mexico begins one month earlier
      than in the Mediterranean Sea. Western bluefin tuna caught in the peak of the
      spawning season (May) showed a similar spawning frequency (60%) to the spawning
      peak observed in the Mediterranean Sea (June). Fecundity for the Gulf of Mexico
      fish (28.14 eggs . g(-1)) was lower but not significantly different than for fish
      sampled in the Mediterranean Sea (45.56 eggs . g(-1)). Our study represents the
      first comparative histological analysis of the eastern and western spawning
      stocks whose findings, combined with new determinations of size/age at maturity
      and possible alternative spawning areas, might suggest basic life history
      attributes warrant further scientific and management attention.

PMID- 24911974
TI  - Time-delayed subsidies: interspecies population effects in salmon.
AB  - Cross-boundary nutrient inputs can enhance and sustain populations of organisms
      in nutrient-poor recipient ecosystems. For example, Pacific salmon (Oncorhynchus
      spp.) can deliver large amounts of marine-derived nutrients to freshwater
      ecosystems through their eggs, excretion, or carcasses. This has led to the
      question of whether nutrients from one generation of salmon can benefit juvenile
      salmon from subsequent generations. In a study of 12 streams on the central coast
      of British Columbia, we found that the abundance of juvenile coho salmon was most
      closely correlated with the abundance of adult pink salmon from previous years.
      There was a secondary role for adult chum salmon and watershed size, followed by
      other physical characteristics of streams. Most of the coho sampled emerged in
      the spring, and had little to no direct contact with spawning salmon nutrients at
      the time of sampling in the summer and fall. A combination of techniques suggest
      that subsidies from spawning salmon can have a strong, positive, time-delayed
      influence on the productivity of salmon-bearing streams through indirect effects
      from previous spawning events. This is the first study on the impacts of
      nutrients from naturally-occurring spawning salmon on juvenile population
      abundance of other salmon species. 

PMID- 24911975
TI  - Acute aerobic exercise increases cortical activity during working memory: a
      functional MRI study in female college students.
AB  - There is increasing evidence that acute aerobic exercise is associated with
      improved cognitive function. However, neural correlates of its cognitive
      plasticity remain largely unknown. The present study examined the effect of a
      session of acute aerobic exercise on working memory task-evoked brain activity as
      well as task performance. A within-subjects design with a counterbalanced order
      was employed. Fifteen young female participants (M = 19.56, SD = 0.81) were
      scanned using functional magnetic resonance imaging while performing a working
      memory task, the N-back task, both following an acute exercise session with 20
      minutes of moderate intensity and a control rest session. Although an acute
      session of exercise did not improve behavioral performance, we observed that it
      had a significant impact on brain activity during the 2-back condition of the N
      back task. Specifically, acute exercise induced increased brain activation in the
      right middle prefrontal gyrus, the right lingual gyrus, and the left fusiform
      gyrus as well as deactivations in the anterior cingulate cortexes, the left
      inferior frontal gyrus, and the right paracentral lobule. Despite the lack of an
      effect on behavioral measures, significant changes after acute exercise with
      activation of the prefrontal and occipital cortexes and deactivation of the
      anterior cingulate cortexes and left frontal hemisphere reflect the improvement
      of executive control processes, indicating that acute exercise could benefit
      working memory at a macro-neural level. In addition to its effects on reversing
      recent obesity and disease trends, our results provide substantial evidence
      highlighting the importance of promoting physical activity across the lifespan to
      prevent or reverse cognitive and neural decline. 

PMID- 24911976
TI  - Pannexin-1 is blocked by its C-terminus through a delocalized non-specific
      interaction surface.
AB  - The Pannexin-1 (Panx1) channel is known to become activated under a variety of
      physiological conditions resulting in the release of medium-sized molecules such
      as ATP and amino acids from the cell. The detailed molecular mechanism of
      activation of the channel resulting in the opening of the Pannexin pore is poorly
      understood. The best-studied gating mechanism is caspase-3/7-mediated cleavage
      and truncation of the c-terminus. In the absence of caspase-cleavage, the c
      terminal peptide maintains the channel in the closed state, possibly by directly
      plugging the pore from the intracellular side. We sought to understand in detail
      the part of the c-terminus necessary for this interaction by alanine-scanning and
      truncation mutagenesis of the c-terminal gating peptide. These experiments
      demonstrate that no single amino acid side-chain is necessary for this
      interaction. In fact, replacing blocks of 10-12 amino acids in different parts of
      the c-terminal peptide with alanines fails to disrupt the ability of the c
      terminus to keep the channel closed. Surprisingly, even replacing the entire c
      terminal gating peptide with a scrambled peptide of the same length maintains the
      interaction in some cases. Further analysis revealed that the interaction
      surface, while delocalized, is located within the amino-terminal two-thirds of
      the c-terminal peptide. Such a delocalized and potentially low-affinity
      interaction surface is allowed due to the high effective concentration of the c
      terminal peptide near the inner vestibule of the pore and likely explains why
      this region is poorly conserved between species. This type of weak interaction
      with a tethered gating peptide may be required to maintain high-sensitivity to
      caspase-dependent activation. 

PMID- 24911977
TI  - Permethrin alters adipogenesis in 3T3-L1 adipocytes and causes insulin resistance
      in C2C12 myotubes.
AB  - Pyrethroids are a class of insecticides structurally derived from the naturally
      occurring insecticides called pyrethrins. Along with emerging evidence that
      exposure to insecticides is linked to altered weight gain and glucose
      homeostasis, exposure to pyrethroids has been linked to altered blood glucose
      levels in humans. Thus, the purpose of this study was to determine the role of
      permethrin on lipid and glucose metabolisms. Permethrin was treated to 3T3-L1
      adipocytes and C2C12 myoblasts to determine its role in lipid and glucose
      metabolisms, respectively. Permethrin treatment resulted in increased expression
      of key markers of adipogenesis and lipogenesis in adipocytes. Permethrin
      significantly reduced insulin-stimulated glucose uptake in myotubes. This is the
      first report on the role of permethrin in altered lipid metabolism in adipocytes
      and impaired glucose homeostasis in myotubes. These results may help elucidate
      fundamental underlying mechanisms between insecticide exposure, particularly
      permethrin, and potential risk of developing obesity and its comorbidities. 

PMID- 24911978
TI  - Measurement of phthalates in skin wipes: estimating exposure from dermal
      absorption.
AB  - This study has determined the levels of six phthalates (dimethyl phthalate (DMP),
      diethyl phthalate (DEP), di(isobutyl) phthalate (DiBP), di(n-butyl) phthalate
      (DnBP), butyl benzyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP)) in
      skin wipes; examined factors that might influence the levels, including body
      location, time of sampling, and hand-washing; and estimated dermal absorption
      based on the measured levels. Skin wipes were collected from the forehead,
      forearm, back-of-hand, and palm of 20 participants using gauze pads moistened
      with isopropanol. DiBP, DnBP, and DEHP were most frequently detected; DEHP levels
      were substantially higher than DnBP and DiBP levels, and DnBP levels were
      somewhat lower than DiBP levels. The levels differed at different body locations,
      with palm > back-of-hand > forearm >= forehead. Repeated wipe sampling from six
      participants over a 1 month period indicated that levels at the same body
      location did not vary significantly. The estimated median total dermal absorption
      from skin surface lipids on the palm, back-of-hand, arm, and head are 0.48, 0.68,
      and 0.66 (MUg/kg)/day for DiBP, DnBP, and DEHP, respectively. These estimates are
      roughly 10-20% of the total uptake reported for Chinese adults and suggest that
      dermal absorption contributes significantly to the uptake of these phthalates.
      Washing with soap and water removed more than 50% of the phthalates on the hands
      and may be a useful tool in decreasing aggregate phthalate exposure. 

PMID- 24911979
TI  - Effect of written emotional disclosure on secondary hyperalgesia in women with
      trauma history.
AB  - OBJECTIVE: This study investigated the effects of written emotional disclosure on
      a model of chronic pain in healthy women with and without trauma history. METHOD:
      Participants were prescreened for their trauma history (N = 78) and randomized to
      a disclosure or a control writing condition. Pain testing occurred either 1 day
      or 1 month after disclosure. Capsaicin was applied to the forearm to evoke
      spontaneous burning pain at the application site and mechanical secondary
      hyperalgesia in the surrounding untreated skin. RESULTS: As hypothesized, the
      effect of disclosure on the area and intensity of secondary hyperalgesia depended
      on trauma history and time of testing (F(1,69) >= 7.37, p = .008). Disclosure
      increased secondary hyperalgesia in participants with trauma history compared
      with those without trauma when testing occurred 1 day after writing (F(1,69) >=
      5.27, p <= .025), whereas the opposite pattern was observed 1 month later
      (F(1,69) >= 4.88, p <= .031). Of the participants with trauma history in the
      disclosure condition, secondary hyperalgesia was reduced at 1 month compared with
      1 day after writing (p = .001). Moreover, greater use of positive emotional words
      predicted reduced secondary hyperalgesia at 1 month (beta = -0.71, p = .022). In
      contrast, disclosure had no effect on spontaneous pain. CONCLUSIONS: Disclosure
      modulates secondary hyperalgesia observed in women with trauma history, producing
      a short-term enhancement and a long-term reduction. This suggests that disclosure
      has a long-term protective effect that reduces sensitization of pain, which may
      explain the therapeutic effects of disclosure in patients with chronic pain.

PMID- 24911980
TI  - Extreme genetic heterogeneity among the nine major tribal Taiwanese island
      populations detected with a new generation Y23 STR system.
AB  - The Taiwanese aborigines have been regarded as the source populations for the
      Austronesian expansion that populated Oceania to the east and Madagascar off
      Africa to the West. Although a number of genetic studies have been performed on
      some of these important tribes, the scope of the investigations has been limited,
      varying in the specific populations examined as well as the maker systems
      employed. This has made direct comparison among studies difficult. In an attempt
      to alleviate this lacuna, we investigate, for the first time, the genetic
      diversity of all nine major Taiwanese aboriginal tribes (Ami, Atayal, Bunun,
      Rukai, Paiwan, Saisat, Puyuma, Tsou and Yami) utilizing a new generation
      multiplex Y-STR system that allows for the genotyping of 23 loci from a single
      amplification reaction. This comprehensive approach examining 293 individuals
      from all nine main tribes with the same battery of forensic markers provides for
      the much-needed equivalent data essential for comparative analyses. Our results
      have uncovered that these nine major aboriginal populations exhibit limited
      intrapopulation genetic diversity and are highly heterogeneous from each other,
      possibly the result of endogamy, isolation, drift and/or unique ancestral
      populations. Specifically, genetic diversity, discrimination capacity, fraction
      of unique haplotypes and the most frequent haplotypes differ among the nine
      tribes, with the Tsou possessing the lowest values for the first three of these
      parameters. The phylogenetic analyses performed indicate that the genetic
      diversity among all nine tribes is greater than the diversity observed among the
      worldwide reference populations examined, indicating an extreme case of genetic
      heterogeneity among these tribes that have lived as close neighbors for thousands
      of years confined to the limited geographical area of an island. 

PMID- 24911981
TI  - Point of care testing for measurement of white blood cell count and C-reactive
      protein levels in blood.

PMID- 24911982
TI  - Lessons from the war on dietary fat.
AB  - Conventional dietary guidelines put forth by health care institutions and
      providers for the past 40 years have stressed the importance of reducing the
      amount of dietary fat consumed. Such a diet is purported to mitigate metabolic
      risk factors and optimize the ability to achieve or maintain a healthy body
      weight. However, over the past 35 years obesity rates in the United States have
      risen dramatically though the level of dietary fat consumed by U.S. adults has
      fallen. This review examines the potential reasons for this paradox. Various meta
      analyses, controlled trials, and cohort studies have demonstrated that reducing
      dietary fat intake provides for very little weight loss unless accompanied by
      equal or greater reductions in total energy intake. Due to both psychological
      (e.g., the tendency for people to eat more of what they consider low fat) and
      physiological (e.g., the low satiety that accompanies carbohydrate intake)
      factors, reducing total caloric intake while simultaneously reducing fat intake
      is a difficult challenge. Further, reductions in total carbohydrate intake,
      increases in protein intake, and adoption of a Mediterranean diet seem to be more
      effective in inducing weight loss than reductions in fat intake. Traditional
      claims that simply reducing dietary fat will improve metabolic risk factors are
      also not borne out by research. There is some evidence that replacing dietary
      saturated fat with unsaturated fat may improve metabolic risk factors, but that
      research is not conclusive. TEACHING POINTS: * Over the past 40 years, Americans
      have decreased the percentage of calories they get from dietary fat while rates
      of overweight and obesity have risen dramatically. * It appears that a decrease
      in total dietary fat in ad libitum diets may induce a very small decrease in body
      weight. * Evidence suggests that reductions in total dietary fat intake often
      occur in conjunction with an increase in total caloric intake. * It seems
      reasonable to conclude that guiding the public to simply reduce dietary fat
      intake is an ineffective method to mitigate the rise in obesity and improve
      public health.

PMID- 24911983
TI  - Estrogen signalling in the pathogenesis of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a multifactorial eye disease that is
      associated with aging, family history, smoking, obesity, cataract surgery,
      arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender
      has commonly been classified as a weak or inconsistent risk factor for AMD. This
      disease is characterized by degeneration of retinal pigment epithelial (RPE)
      cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage
      and death of photoreceptor cells and central visual loss. Pathogenesis of AMD
      involves constant oxidative stress, chronic inflammation, and increased
      accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti
      inflammatory capacity and it regulates signaling pathways that are involved in
      the pathogenesis of AMD. In this review, we discuss potential cellular signaling
      targets of estrogen in retinal cells and AMD pathology.

PMID- 24911984
TI  - Hypertrabeculation vs left ventricular noncompaction on echocardiogram: a reason
      to restrict athletic participation?
AB  - IMPORTANCE: Left ventricular noncompaction (LVNC) is a rare cause of progressive
      cardiomyopathy thought to result from incomplete myocardial development. It has
      been associated with an increased risk of sudden death, especially in those with
      a depressed left ventricular ejection fraction. Thus, the current recommendation
      for patients with this diagnosis is restriction from participation in competitive
      sports. OBSERVATIONS: An asymptomatic 18-year-old African American collegiate
      football player had a murmur on his preparticipation physical examination.
      Subsequent cardiology workup revealed hypertrabeculation vs LVNC. Second and
      third opinions were sought from national experts in the field: one gave the
      diagnosis of LVNC and recommended restriction; the other gave the diagnosis of
      hypertrabeculation. After a family meeting including the player, mother, team
      physician, and consulting cardiologist, the player was permitted to participate
      in football. CONCLUSIONS AND RELEVANCE: Distinguishing between pathologic LVNC
      and physiologic hypertrabeculation is a diagnostic challenge and is becoming
      increasingly commonplace with enhanced echocardiography and magnetic resonance
      imaging modalities. Given the limited data on such patients, careful workup and
      discussion between patient and providers is required.

PMID- 24911985
TI  - Contraceptive use in women under 20 years of age: A study in Iran.
AB  - Contraception methods are one of the most important factors in population
      control. A choice of the safe and effective methods available to adolescents may
      guarantee their safety. The purpose of the present study was to evaluate the rate
      and kind of contraceptive methods used by women under 20 years of age and finding
      the related demographic factors. A total of 500 women who finished the study were
      evaluated regarding the rate of contraceptive use, which method was used and the
      probable demographic-related factors. More than half (51.6%) of the women used
      contraception. The most common method was breast-feeding (27.1%), although only
      2.8% had enough knowledge about breast-feeding as a contraceptive method. Other
      common methods used were IUD (intrauterine device) (24.8%) and the withdrawal
      method (24.8%). The usage of contraception was directly related to the number of
      pregnancies, the age of marriage and the woman's age at first pregnancy. It
      related indirectly to the level of education, the number of brothers and sisters
      and size of the family, socioeconomic status, the age of the mother when married
      and the age of menarche.

PMID- 24911986
TI  - Child sexual abuse in the context of the Roman Catholic Church: a review of
      literature from 1981-2013.
AB  - Child sexual abuse in the Catholic Church has been increasingly recognized as a
      problem not limited to individual institutions. Recent inquiry commission reports
      provide substantial information on offense dynamics, but their conclusions have
      not been synthesized with empirical research to date. The aim of this systematic
      literature review was to bring together key findings and identify gaps in the
      evidence base. The three main focus points were (a) types of publications and
      methodology used, (b) frequency information on child sexual abuse in the Catholic
      Church, (c) individual factors in offending, and (d) institutional factors in
      offending. It was found that reports, legal assessments, and research on child
      sexual abuse within the Catholic Church provide extensive descriptive and
      qualitative information for five different countries. This includes individual
      psychological factors (static risk predictors, multiple trajectories) and
      institutional factors (opportunity, social dynamics) as well as prevalence rates
      illustrating a high "dark figure" of child sexual abuse. 

PMID- 24911987
TI  - Occupational therapist practice patterns in relation to clients with cognitive
      impairment following acquired brain injury.
AB  - Abstract Primary objective: To describe Swedish occupational therapist practice
      patterns for clients with cognitive impairment following acquired brain injury.
      RESEARCH DESIGN: A cross-sectional stratified random sample of 462 occupational
      therapists. METHODS: An online questionnaire was used to collect data. MAIN
      RESULTS: The predominant practice pattern was the use of ADL-activities for
      assessment and therapy regardless of whether limitations in occupational
      performance or cognitive function were assessed or whether the approach was
      remedial or compensatory. For assessment, general ADL-instruments were used more
      often than instruments that assessed cognitive function. Instruments were used
      less often within municipal rehabilitation facilities compared to regional,
      county and primary care facilities. The most common focus of the therapies was in
      regard to abilities related to executive functioning. Another prominent practice
      pattern was a collaborative approach involving clients, relatives and other
      staff. The theories used in practice were, to a large extent, general in nature
      and did not focus specifically on cognitive functioning. CONCLUSIONS: Swedish
      occupational therapy practice for clients with cognitive impairments following
      acquired brain injury focuses highly on occupational performance. Therapies
      targeting executive functioning seem particularly important in practice and a
      collaborative approach involving clients, relatives and other staff is a
      prominent feature in practice.

PMID- 24911988
TI  - Saudi women's beliefs on the use of car infant restraints: a qualitative study.
AB  - OBJECTIVE: The focus of this study was to identify the salient beliefs of
      pregnant women in Saudi Arabia that may influence their intentions to use infant
      restraints for their children. These beliefs were later used to inform a
      subsequent quantitative study. METHODS: This qualitative study employed Ajzen's
      theory of planned behavior to elicit the salient behavioral, normative, and
      control beliefs of Saudi pregnant women regarding the use of infant restraints
      for their future children. Twenty-five pregnant women participated in 2 focus
      groups conducted in June 2013 at Dallah Hospital in Riyadh. RESULTS: Lack of
      health education and law enforcement; cultural pressure and traditions; counsel
      from family, specifically from husbands and mothers; desire to stay close to the
      child; family size; and car size were key factors in deciding whether or not to
      use car seats; the high cost of car seats was not. CONCLUSIONS: Aside from
      providing awareness to future mothers and the general public, health
      interventions should target the specific beliefs identified in this study.
      Because participants identified husbands as significant referents, further
      studies are needed to examine the husbands' attitudes and beliefs.

PMID- 24911991
TI  - Lower-leg compression, running mechanics, and economy in trained distance
      runners.
AB  - The efficacy of and mechanisms behind the widespread use of lower-leg compression
      as an ergogenic aid to improve running performance are unknown. The purpose of
      this study was to examine whether wearing graduated lower-leg compression sleeves
      during exercise evokes changes in running economy (RE), perhaps due to altered
      gait mechanics. Sixteen highly trained male distance runners completed 2 separate
      RE tests during a single laboratory session, including a randomized-treatment
      trial of graduated calf-compression sleeves (CS; 15-20 mm Hg) and a control trial
      (CON) without compression sleeves. RE was determined by measuring oxygen
      consumption at 3 constant submaximal speeds of 233, 268, and 300 m/min on a
      treadmill. Running mechanics were measured during the last 30 s of each 4-min
      stage of the RE test via wireless triaxial 10-g accelerometer devices attached to
      the top of each shoe. Ground-contact time, swing time, step frequency, and step
      length were determined from accelerometric output corresponding to foot-strike
      and toe-off events. Gait variability was calculated as the standard deviation of
      a given gait variable for an individual during the last 30 s of each stage. There
      were no differences in VO2 or kinematic variables between CON and CS trials at
      any of the speeds. Wearing lower-leg compression does not alter the energetics of
      running at submaximal speeds through changes in running mechanics or other means.
      However, it appears that the individual response to wearing lower-leg compression
      varies greatly and warrants further examination. 

PMID- 24911990
TI  - Novel role of Cdc42 and RalA GTPases in TNF-alpha mediated secretion of CCL2.
AB  - Transendothelial migration of autoreactive leukocytes into peripheral nerves is
      an early pathological hallmark of acute inflammatory demyelinating polyneuropathy
      (AIDP), a North American and European variant of Guillain-Barre Syndrome. Whereas
      the clinical management of AIDP is currently limited to non-selective immune
      modulating therapies, recent experimental studies support selective targeting of
      leukocyte trafficking as a promising alternative therapeutic strategy. Here,
      using a combination of targeted siRNA knockdown and pharmacological inhibitors,
      we report a novel role of both Cdc42 and RalA GTPases in facilitating TNF-alpha
      mediated CCL2 trafficking and release from immortalized rat peripheral nerve
      microvascular endoneurial endothelial cells. These findings raise interest in
      Cdc42 and RalA GTPases as potential therapeutic targets for the management of
      autoimmune inflammatory peripheral nerve disease. 

PMID- 24911989
TI  - Executive dysfunction and reward dysregulation: a high-density electrical mapping
      study in cocaine abusers.
AB  - Executive function deficits and reward dysregulation, which mainly manifests as
      anhedonia, are well documented in drug abusers. We investigated specific aspects
      of executive function (inhibitory control and cognitive control), as well as
      anhedonia, in a cohort of current cocaine abusers in order to ascertain to what
      extent these factors are associated with more severe drug dependence.
      Participants filled out questionnaires relating to anhedonia and their addiction
      history. Participants also performed a response inhibition task while high
      density event-related potentials (ERPs) were recorded. Electrophysiological
      responses to successful inhibitions (N2/P3 components) and to commission errors
      (ERN/Pe components) were compared between 23 current users of cocaine and 27 non
      using controls. A regression model was performed to determine the association of
      our measures of reward dysregulation and executive function with addiction
      severity. As expected, cocaine users performed more poorly than controls on the
      inhibitory control task and showed significant electrophysiological differences.
      They were also generally more anhedonic than controls. Higher levels of anhedonia
      were associated with more severe substance use, whereas the level of executive
      dysfunction was not associated with more severe substance use. However, N2
      amplitude was associated with duration of drug use. Further, inhibitory control
      and anhedonia were correlated, but only in controls. These data suggest that
      while executive dysfunction characterizes drug abuse, it is anhedonia,
      independent of executive dysfunction, that is most strongly associated with more
      severe use. 

PMID- 24911992
TI  - In vitro--in silico--in vivo drug absorption model development based on
      mechanistic gastrointestinal simulation and artificial neural networks:
      nifedipine osmotic release tablets case study.
AB  - In vitro--in vivo correlations (IVIVC) are generally accepted as a valuable tool
      in modified release formulation development aimed at (i) quantifying the in vivo
      drug delivery profile and formulation related effects on absorption; (ii)
      establishing clinically relevant dissolution specifications and (iii) supporting
      the biowaiver claims. The aim of the present study was to develop relevant IVIVC
      models based on mechanistic gastrointestinal simulation (GIS) and artificial
      neural network (ANN) analysis and to evaluate their applicability and usefulness
      in biopharmaceutical drug characterisation. Nifedipine osmotic release tablets
      were selected as model drug product on the basis of their robustness, dissolution
      limited drug absorption and the availability of relevant literature data.
      Although the osmotic release tablets have been designed to be robust against the
      influence of physiological conditions in the gastrointestinal tract, notable
      differences in nifedipine dissolution kinetics were observed depending on the in
      vitro experimental conditions employed. The results obtained indicate that both
      GIS and ANN model developed were sensitive to input kinetics represented by the
      in vitro profiles obtained under various experimental conditions. Different in
      silico approaches may be successfully employed in the in vitro--in silico--in
      vivo model development. However, the results obtained may differ and relevant
      outcomes are sensitive to the methodology employed.

PMID- 24911993
TI  - Decision for biological treatment in real life is more strongly associated with
      the Psoriasis Area and Severity Index (PASI) than with the Dermatology Life
      Quality Index (DLQI).
AB  - BACKGROUND: Following the establishment of the National Quality Registry for
      systemic psoriasis treatment (PsoReg), the two psoriasis outcome measurements,
      Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index
      (DLQI), are now integrated in clinical practice in Sweden. According to current
      guidelines, the initiation of a biological treatment should depend on a
      combination of the physician's (PASI) and the patients' assessment of the disease
      impact on a health-related quality of life measure (DLQI). OBJECTIVE: To evaluate
      if either of the two measures, PASI or DLQI, is more strongly associated with
      initiation of biological therapy. METHODS: The study is based on 2216 patients
      suffering from moderate to severe psoriasis who were biological naive at
      enrolment to PsoReg. The relationship between the two measures PASI and DLQI and
      initiation of biological treatment (as outcome) were estimated by a logistic
      regression and a Cox proportional hazard's model with combinations of PASI and
      DLQI as independent variables. RESULTS: The adjusted regression models showed
      that patients with high PASI score and low DLQI score had a higher chance to
      receive biological treatment compared to patients with low PASI score and high
      DLQI score. CONCLUSION: The decision to initiate biological treatment is more
      strongly associated with PASI than with DLQI. However, since the DLQI reflects
      both socio-economic costs and patient suffering better than PASI, the relevance
      of the DLQI may be underestimated in clinical practice.

PMID- 24911994
TI  - Spin waves and domain wall modes in curved magnetic nanowires.
AB  - The confinement of spin waves in inhomogeneous fields and spin wave interaction
      with domain walls has attracted interest due to possible applications in
      magnonics. We investigate spin waves in curved ferromagnetic nanowires. The field
      dispersion and localization of spin waves is revealed by comparison to known
      modes in stripes and taking into account the specific field reversal of the
      curved wire. In small wires we find a strongly altered mode spectrum in a certain
      field regime. Micromagnetic simulations show an extended domain wall within the
      wire in this field region. The domain wall shows several dynamic modes and
      changes the remaining spin wave modes. We find mode suppression as well as newly
      arising modes due to the strong inhomogenous internal field of the wall. 

PMID- 24911995
TI  - Multicomponent reaction for the first synthesis of 2,2-dialkyl- and 2-alkyl-2
      aralkyl-5,6-diaryl-2H-1,3-thiazines as scaffolds for various 3,4-dihydro-2H-1,3
      thiazine derivatives.
AB  - A two-step sequence for the synthesis of various 3,4-dihydro-2H-1,3-thiazines is
      presented. In the first step, 2H-1,3-thiazines were prepared by a new
      multicomponent reaction (MCR). Starting from beta-chlorovinyl aldehydes, this MCR
      offers an efficient and facile access to 2,2-dialkyl- and 2-alkyl-2-aralkyl-5,6
      diaryl-2H-1,3-thiazines. The potential of these products in subsequent reactions
      was verified by the conversion to 3,4-dihydro-2H-1,3-thiazine-containing
      bisamides, beta-lactams, and methoxy amides. 

PMID- 24911996
TI  - Theory of structural transformation in lithiated amorphous silicon.
AB  - Determining structural transformations in amorphous solids is challenging due to
      the paucity of structural signatures. The effect of the transitions on the
      properties of the solid can be significant and important for applications.
      Moreover, such transitions may not be discernible in the behavior of the total
      energy or the volume of the solid as a function of the variables that identify
      its phases. These issues arise in the context of lithiation of amorphous silicon
      (a-Si), a promising anode material for high-energy density batteries based on
      lithium ions. Recent experiments suggest the surprising result that the
      lithiation of a-Si is a two-phase process. Here, we present first-principles
      calculations of the structure of a-Si at different lithiation levels. Through a
      detailed analysis of the short and medium-range properties of the amorphous
      network, using Voronoi-Delaunay methods and ring statistics, we show that a-LixSi
      has a fundamentally different structure below and above a lithiation level
      corresponding to x ~ 2.

PMID- 24911997
TI  - Peptide-catalyzed kinetic resolution of planar-chiral metallocenes.
AB  - Kinetic resolution of racemic planar-chiral metallocenes was performed through
      the conjugate addition of a nucleophile to the enal part of substrates. While no
      enantiomeric discrimination was found with low-molecular-weight organocatalysts,
      a properly designed resin-supported peptide catalyzed the reaction in a highly
      selective manner. 

PMID- 24911998
TI  - A 'complex solution' to a 'complex' problem: tackling the complexity of cancer
      with botanicals.
AB  - Several biological and physical factors confer complexity on cancer, which may be
      responsible for its associated morbidity. The successful management of this
      hyperproliferative disease is beyond the realm of therapeutics that may include
      the use of a single or at times a combination of treatment modalities. It is
      apparent that prevention with complex agents such as botanicals could serve as a
      possible potential solution. The present review focuses on the aspects of cancer
      that contribute toward making it an extremely complex disease and that may be
      tackled effectively with the use of 'multicomponent' botanicals. 

PMID- 24911999
TI  - Cigarette smoke inhalation and risk of lung cancer: a case-control study in a
      large Japanese population.
AB  - Several studies have shown that cigarette smoke inhalation is associated with an
      increased risk of lung cancer (LC) in European populations. The aim of our study
      was to clarify the relationship between cigarette smoke inhalation and the risk
      of LC in a Japanese population. We carried out a large case-control study of
      cigarette smoking and the risk of LC in Japan. Cases were newly diagnosed
      patients with histologically confirmed LC (n=653). Controls (n=1281) included
      hospital controls (n=453) and community-based controls (n=828). Odds ratios (OR)
      and 95% confidence intervals (CI) were derived from unconditional logistic
      regression analysis, adjusted for basic confounding variables including age, sex,
      drinking status, fruit and vegetable intake, family history of LC, occupation,
      and years of education. Compared with never smokers, ORs for ever smokers who do
      not inhale cigarette smoke (noninhalation) and ever smokers who inhale cigarette
      smoke (inhalation) were 1.72 (95% CI: 1.15-2.59) and 3.28 (95% CI: 2.38-4.53),
      respectively, when adjusted for basic confounding variables. When the analysis
      was restricted to ever smokers, the OR adjusted for basic confounding factors and
      pack-year of the risk of LC in the inhalation group was significantly higher than
      that in the noninhalation group. OR for the inhalation group compared with the
      noninhalation group was 1.52 (95% CI: 1.06-2.18, P=0.021). A similar pattern was
      observed in subcategory analyses for adenocarcinoma, squamous cell carcinoma and
      small cell carcinoma, and other histological types, although without statistical
      significance. Our case-control study showed that inhalation of cigarette smoke is
      a significant risk for LC independent from pack-years in a Japanese population. 

PMID- 24912000
TI  - Evolutionary histories of soil fungi are reflected in their large-scale
      biogeography.
AB  - Although fungal communities are known to vary along latitudinal gradients,
      mechanisms underlying this pattern are not well-understood. We used high
      throughput sequencing to examine the large-scale distributions of soil fungi and
      their relation to evolutionary history. We tested the Tropical Conservatism
      Hypothesis, which predicts that ancestral fungal groups should be more restricted
      to tropical latitudes and conditions than would more recently derived groups. We
      found support for this hypothesis in that older phyla preferred significantly
      lower latitudes and warmer, wetter conditions than did younger phyla. Moreover,
      preferences for higher latitudes and lower precipitation levels were
      significantly phylogenetically conserved among the six younger phyla, possibly
      because the older phyla possess a zoospore stage that is vulnerable to drought,
      whereas the younger phyla retain protective cell walls throughout their life
      cycle. Our study provides novel evidence that the Tropical Conservatism
      Hypothesis applies to microbes as well as plants and animals. 

PMID- 24912001
TI  - Co-existence of primary fallopian tube carcinoma and uterine carcinosarcoma.

PMID- 24912002
TI  - Functional group effects on the enthalpy of adsorption for self-assembly at the
      solution/graphite interface.
AB  - The thermodynamics of self-assembly have long been explored by either
      experimental or theoretical investigations which are often unable to account for
      all the factors influencing the assembly process. This work interrogates the
      thermodynamics of self-assembly at a liquid/solid interface by measuring the
      enthalpy of adsorption encompassing analyte-analyte, analyte-solvent, analyte
      substrate, and solvent-substrate interactions. Comparison of the experimental
      data with computed lattice energies for the relevant monolayers across a series
      of aliphatic analytes reveals similar ordering within the series, with the
      exceptions of the fatty acid and bromoalkane adsorbates. Such a discrepancy could
      arise when the lattice energies do not account for important interactions, such
      as analyte-analyte interactions in solution. Flow microcalorimetry provides a
      uniquely inclusive view of the thermodynamic events relevant to self-assembly at
      the liquid/solid interface. 

PMID- 24912003
TI  - Choroidal thickness in ocular sarcoidosis during quiescent phase using enhanced
      depth imaging optical coherence tomography.
AB  - PURPOSE: To evaluate the choroidal thickness in patients with ocular sarcoidosis
      during quiescent phase using enhanced depth imaging optical coherence tomography
      (EDI-OCT) and comparing it with normal subjects. METHOD: Eighteen eyes of 9
      patients with ocular sarcoidosis (8 women, 1 man, mean age: 59.12 +/- 18.49
      years) were enrolled in this study. Their subfoveal choroidal thickness was
      measured using EDI-OCT in the quiescent phase of uveitis, and compared with the
      age-, sex-, and spherical equivalent-matched normal subjects (6 women, 3 men,
      mean age: 59.6 +/- 14.22 years). RESULTS: The mean subfoveal choroidal thickness
      was 281.76 +/- 88.1 um in patients with sarcoidosis and 342.32 +/- 71.02 um in
      controls. Significant differences were found at points between nasal 1500 um and
      temporal 1000 um to the fovea between patients and control group (p = 0.002, at
      fovea). CONCLUSIONS: Patients with ocular sarcoidosis had thinner choroids in the
      quiescent phases when compared to normal subjects.

PMID- 24912004
TI  - Cardiac platypnea-orthodeoxia syndrome: an often unrecognized malady.
AB  - Platypnea-orthodeoxia syndrome (POS) is a rare but clinically important form of
      dyspnea. The syndrome is characterized by dyspnea and arterial oxygen
      desaturation that occurs in the upright position and improves with recumbency. In
      cardiac POS, an atrial septal defect or patent foramen ovale allows communication
      between the right- and left-sided circulations. A second defect, such as a
      dilated aorta, prominent eustachian valve, or pneumonectomy, then contributes to
      right-to-left shunting through the interatrial connection. Diagnosis is made
      through pulse oximetry to confirm orthodeoxia and through transesophageal
      echocardiography with bubble study to visualize the shunt. Although data are
      limited for this rare syndrome, percutaneous closure has thus far proven safe and
      effective. 

PMID- 24912005
TI  - Evaluation of oxidative stress markers in aqueous humor of primary open angle
      glaucoma and primary angle closure glaucoma patients.
AB  - PURPOSE: The present study was designed to determine the levels of antioxidant
      enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and non
      enzymatic antioxidants (vitamins C and E) in aqueous humor of primary open angle
      glaucoma (POAG) and primary angle closure glaucoma (PACG) patients. MATERIALS AND
      METHODS: In this study, aqueous humor of POAG (n = 30) and PACG (n = 30) patients
      was obtained. For control, aqueous humor of 30 age-matched cataract patients (n =
      30) was collected. Activities of antioxidant enzymes and non-enzymatic
      antioxidants levels were measured spectrophotometrically. RESULTS: A significant
      increase in superoxide dismutase (SOD) and glutathione peroxidase (GPx)
      activities was found in aqueous humor of POAG and PACG patients as compared to
      cataract patients (p < 0.001). No significant changes were observed in catalase
      activity. The levels of vitamins C and E were significantly lower in the aqueous
      humor of POAG and PACG as compared to cataract patients (p < 0.001). CONCLUSION:
      These results suggest that a significant increase in oxidative stress may play a
      role in the pathogenesis of POAG and PACG. Determination of oxidative stress in
      aqueous humor may help in understanding the course of this disease, and oxidative
      damage might be a relevant target for both prevention and therapy.

PMID- 24912006
TI  - Associations of killer cell immunoglobulin like receptors with rheumatoid
      arthritis among North Indian population.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory
      disease of unknown etiology. Killer cell immunoglobulin-like receptors (KIR)
      expressed on surface of natural killer cells and CD28 null T-cells which are
      present in synovial membrane of RA. The present study has evaluated associations
      of KIR genes with RA among North Indian population from Uttar Pradesh. MATERIALS
      AND METHODS: KIR genotypes were determined in 100 RA cases and 100 healthy
      controls using sequence specific primer polymerase chain reaction (PCR-SSP)
      method. RESULTS: RA cases positive for KIR3DS1 (OR = 1.17, p-value = 0.0498) and
      KIR2DS2 (OR = 2.21, p-value = 0.0120) showed risk associations. While, KIR2DL2
      (OR = 0.40, p-value = 0.0026), KIR2DL3 (OR = 0.44, p-value = 0.0283) and KIR3DL1
      (OR=0.32, p-value = 0.0012) showed protective associations. Increased incidence
      of BB genotype (45%) was revealed among cases. Risk association was noted against
      telomeric region (OR = 2.12, p = 0.0120) genes for RA. Pair-wise linkage
      disequilibrium (LD) analysis among RA cases revealed KIR2DS1-2DL1 (D' = 0.83,
      r(2) = 0.36), KIR3DL1-3DS1 (D' = 1, r(2) = 0.58) and KIR2DL1-2DL2 (D' = 1,
      r(2)=0.61) to be in significant LD. KIR3DS1 and KIR2DS3 genes showed significant
      risk associations among RA patients with extra-articular manifestations (OR =
      5.14, p-value = 0.0018; OR = 3.79, p-value = 0.0106) and in limited range of
      motion in affected joints (OR = 14.91, p-value = 0.0001; OR = 2.95, p
      value=0.0126). CONCLUSION: The KIR activating genes have risk association with RA
      in the present study.

PMID- 24912007
TI  - Association of the STAT-6 rs324011 (C2892T) variant but not rs324015 (G2964A),
      with atopic asthma in a Saudi Arabian population.
AB  - BACKGROUND: The signal transducer and activator of transcription 6 (STAT6)
      transduces signals in response to IL-4 and IL-13 cytokine stimulations, resulting
      in many cell-specific responses. Some common STAT6 SNPs were associated with
      asthma predisposition and/or IgE levels, although discrepancies have also been
      reported. OBJECTIVE: To determine whether STAT6 rs324011 and rs324015
      polymorphisms are associated with atopic asthma in Saudi Arabian patients.
      METHODS: A total of 536 Saudi individuals aged 11-70years old (230 atopic
      asthmatics, 306 healthy subjects) were recruited. DNA was purified from
      peripheral blood and genotyping for rs324011 and rs324015 polymorphisms was
      performed by PCR amplification, followed by cycle sequencing of the purified PCR
      fragments using BigDye chain terminator and capillary electrophoresis. RESULTS:
      By the contrast of alleles tests, no significant differences between asthma and
      healthy groups were detected for both variants (rs324011: X(2)=0.25, Pearson's P
      value=0.617; rs324015: X(2)=0.068, Pearson's P=0.814).When testing for genotypes,
      rs324011 homozygous T/T genotype was significantly associated with asthma, when
      the Recessive model is considered (T/T vs. C/C+C/T) (adjusted, OR=2.49, 95%
      CI=1.18-5.25, Pearson's P=0.014(*), Yates' P=0.022(*)). In contrast, rs324015
      variant was not significantly associated with asthma. CONCLUSIONS: Rs324011
      homozygous T/T genotype was significantly associated with asthma risk whereas
      rs324015 genotypes were not in the Saudi population.

PMID- 24912008
TI  - Investigation of gene-gene interactions between CD40 and CD40L in Polish multiple
      sclerosis patients.
AB  - CD40-CD40L interaction is necessary for the activation of both humoral and
      cellular immune response and has been suggested to play a role in the
      pathogenesis of multiple sclerosis (MS). Therefore, we analyzed the combined
      influence of the CD40 and CD40L variants on MS susceptibility and progression on
      well-defined Polish population. Our investigation revealed that CT individuals in
      rs1883832 locus of CD40 possessed almost 1.5-fold higher risk for MS than CC
      individuals (OR = 1.44; 95%CI = 1.03-2.1; p = 0.032), while this risk for TT
      individuals was almost 2.5-fold higher (OR = 2.36; 95%CI = 1.19-4.78; p = 0.014).
      Moreover, for the first time, we observed the association of CD40 gene with MS
      development and progression. We observed that for the rs1883832CC individuals the
      age at diagnosis was on average 2 years lower than for the rs1883832CT and
      rs1883832TT individuals (CI95% = -3.69-(-0.29); p = 0.023). Additionally, we
      detected that individuals with TT and CT genotypes showed lower risk of
      developing secondary progressive course in comparison to those with CC genotype.
      For rs1883832TT individuals this risk was 4-fold lower (HR = 0.24; CI95% = 0.10
      0.53; p = 0.00062). Despite the fact that CD40-CD40L pathway plays a key role in
      development of autoimmune diseases, we were not able to detect gene-gene
      interactions between CD40 and CD40L polymorphisms associated with multiple
      sclerosis.

PMID- 24912009
TI  - Copper-catalyzed enantioselective Friedel-Crafts alkylation of pyrrole with
      isatins.
AB  - The highly enantioselective Friedel-Crafts alkylation of pyrrole with isatins
      catalyzed by the tridentate Schiff base/Cu catalyst was developed.
      Hexafluoroisopropanol (HFIP) was used as a crucial additive to improve the
      enantioselectivity. In the case of N-unprotected isatins, an innovative substrate
      slow-releasing strategy was applied by virtue of a Henry/retro-Henry reaction. 

PMID- 24912010
TI  - Hypoxia/hypercapnia-induced adaptation maintains functional capacity of cord
      blood stem and progenitor cells at 4 degrees C.
AB  - We analyzed the effect of exposure to hypoxic/hypercapnic (HH) gas mixture (5% O2
      /9% CO2 ) on the maintenance of functional cord blood CD34(+) hematopoietic stem
      and progenitor cells in severe hypothermia (4 degrees C) employing the
      physiological and proteomic approaches. Ten-day exposure to HH maintained the Day
      0 (D-0) level of hematopoietic stem cells as detected in vivo on the basis of
      hematopoietic repopulation of immunodeficient mice-short-term scid repopulating
      cells (SRC). Conversely, in the atmospheric air (20% O2 /0.05% CO2 ), usual
      condition used for cell storage at 4 degrees C, stem cell activity was
      significantly decreased. Also, HH doubled the survival of CD34(+) cells and
      committed progenitors (CFCs) with respect to the atmospheric air (60% vs. 30%,
      respectively). Improved cell maintenance in HH was associated with higher
      proportion of aldehyde dehydrogenase (ALDH) positive cells. Cell-protective
      effects are associated with an improved maintenance of the plasma and
      mitochondrial membrane potential and with a conversion to the glycolytic
      energetic state. We also showed that HH decreased apoptosis, despite a sustained
      ROS production and a drop of ATP amount per viable cell. The proteomic study
      revealed that the global protein content was better preserved in HH. This
      analysis identified: (i) proteins sensitive or insensitive to hypothermia
      irrespective of the gas phase, and (ii) proteins related to the HH cell
      protective effect. Among them are some protein families known to be implicated in
      the prolonged survival of hibernating animals in hypothermia. These findings
      suggest a way to optimize short-term cell conservation without freezing.

PMID- 24912011
TI  - Bullying and weapon carrying: a meta-analysis.
AB  - IMPORTANCE: Studies suggest that adolescents involved in bullying are more likely
      to carry weapons than their uninvolved peers. OBJECTIVE: To use meta-analyses to
      determine whether victims, bullies, and bully-victims are more likely to carry
      weapons than uninvolved peers. DATA SOURCES: PsycINFO, ERIC, MEDLINE, LILACS,
      EMBASE, and Dissertation Abstracts International were searched for relevant
      publications (1950 through January 2014). The reference list of a review article
      and reference lists of retrieved articles were checked for further relevant
      studies. STUDY SELECTION: Studies were included if they provided an effect size
      comparing the weapon carrying of adolescent victims, bullies, or bully-victims
      with that of uninvolved peers. Studies that included individuals older than 21
      years were excluded, as were studies that focused on incarcerated youth or youth
      diagnosed as having a psychopathologic condition. DATA EXTRACTION AND SYNTHESIS:
      Studies were coded independently by 2 of us. The agreement rate was 93%. Effect
      sizes were coded that compared victims, bullies, or bully-victims with uninvolved
      peers. Meta-analyses were based on 22 studies for victims (n = 257 179), 15
      studies for bullies (n = 236 145), and 8 studies for bully-victims (n = 199 563).
      MAIN OUTCOMES AND MEASURES: This study focused on weapon carrying among
      adolescents. Hypotheses were formulated before the study. RESULTS: Victims (odds
      ratio, 1.97; 95% CI, 1.62-2.39), bullies (3.25; 2.72-3.89), and bully-victims
      (4.95; 3.77-6.50) were more likely to carry weapons than uninvolved peers.
      Analyses provided no indication of publication bias. Studies conducted in the
      United States found stronger relations between being a bully-victim and weapon
      carrying (odds ratio, 7.84; 95% CI, 6.02-10.21) than studies from other countries
      (3.62; 2.30-5.68; Q1 = 8.401; P = .004). CONCLUSIONS AND RELEVANCE: Involvement
      in bullying as a victim, bully, or bully-victim is related to weapon carrying.

PMID- 24912012
TI  - Exercise is just as important as your medication.

PMID- 24912013
TI  - Myasthenia gravis presenting with dysphagia in an elderly male: a case report.

PMID- 24912014
TI  - Lithium storage properties of pristine and (Mg, Cu) codoped ZnFe2O4
      nanoparticles.
AB  - ZnFe2O4 and MgxCu0.2Zn0.82-xFe1.98O4 (where x = 0.20, 0.25, 0.30, 0.35, and 0.40)
      nanoparticles were synthesized by sol-gel assisted combustion method. X-ray
      diffraction (XRD), FTIR spectroscopy, Raman spectroscopy, scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and Brunauer-Emmett
      Teller (BET) surface area studies were used to characterize the synthesized
      compounds. ZnFe2O4 and the doped compounds crystallize in Fd3m space group. The
      lattice parameter of ZnFe2O4 is calculated to be a = 8.448(3) A, while the doped
      compounds show a slight decrease in the lattice parameter with an increase in the
      Mg content. The particle size of all the compositions are in the range of ~50-80
      nm, and the surface area of the compounds are in the range of 11-12 m(2) g(-1).
      Cyclic voltammetry (CV), galvanostatic cycling, and electrochemical impedance
      spectroscopy (EIS) studies were used to investigate the electrochemical
      properties of the different compositions. The as-synthesized samples at 600 
      degrees C show large-capacity fading, while the samples reheated at 800  degrees
      C show better cycling stability. ZnFe2O4 exhibits a high reversible capacity of
      575 mAh g(-1) after 60 cycles at a current density of 100 mA g(-1).
      Mg0.2Cu0.2Zn0.62Fe1.98O4 shows a similar capacity of 576 mAh g(-1) after 60
      cycles with better capacity retention. 

PMID- 24912015
TI  - Erythrocytes-based synthetic delivery systems: transition from conventional to
      novel engineering strategies.
AB  - INTRODUCTION: Erythrocytes (red blood cells [RBCs]) and artificial or synthetic
      delivery systems such as liposomes, nanoparticles (NPs) are the most investigated
      carrier systems. Herein, progress made from conventional approach of using RBC as
      delivery systems to novel approach of using synthetic delivery systems based on
      RBC properties will be reviewed. AREAS COVERED: We aim to highlight both
      conventional and novel approaches of using RBCs as potential carrier system.
      Conventional approaches which include two main strategies are: i) directly
      loading therapeutic moieties in RBCs; and ii) coupling them with RBCs whereas
      novel approaches exploit structural, mechanical and biological properties of RBCs
      to design synthetic delivery systems through various engineering strategies.
      Initial attempts included coupling of antibodies to liposomes to specifically
      target RBCs. Knowledge obtained from several studies led to the development of
      RBC membrane derived liposomes (nanoerythrosomes), inspiring future application
      of RBC or its structural features in other attractive delivery systems
      (hydrogels, filomicelles, microcapsules, micro- and NPs) for even greater
      potential. EXPERT OPINION: In conclusion, this review dwells upon comparative
      analysis of various conventional and novel engineering strategies in developing
      RBC based drug delivery systems, diversifying their applications in arena of drug
      delivery. Regardless of the challenges in front of us, RBC based delivery systems
      offer an exciting approach of exploiting biological entities in a multitude of
      medical applications.

PMID- 24912016
TI  - Tailoring atropisomeric maleimides for stereospecific [2 + 2] photocycloaddition-
      photochemical and photophysical investigations leading to visible-light
      photocatalysis.
AB  - Atropisomeric maleimides were synthesized and employed for stereospecific [2 + 2]
      photocycloaddition. Efficient reaction was observed under direct irradiation,
      triplet-sensitized UV irradiation, and non-metal catalyzed visible-light
      irradiation, leading to two regioisomeric (exo/endo) photoproducts with complete
      chemoselectivity (exclusive [2 + 2] photoproduct). High enantioselectivity (ee >
      98%) and diastereoselectivity (dr > 99:1%) were observed under the employed
      reaction conditions and were largely dependent on the substituent on the
      maleimide double bond but minimally affected by the substituents on the alkenyl
      tether. On the basis of detailed photophysical studies, the triplet energies of
      the maleimides were estimated. The triplet lifetimes appeared to be relatively
      short at room temperature as a result of fast [2 + 2] photocycloaddition. For the
      visible-light mediated reaction, triplet energy transfer occurred with a rate
      constant close to the diffusion-limited value. The mechanism was established by
      generation of singlet oxygen from the excited maleimides. The high selectivity in
      the photoproduct upon reaction from the triplet excited state was rationalized on
      the basis of conformational factors as well as the type of diradical intermediate
      that was preferred during the photoreaction. 

PMID- 24912017
TI  - Autobiographical reasoning in life narratives buffers the effect of biographical
      disruptions on the sense of self-continuity.
AB  - Personal identity depends on synchronic coherence and diachronic continuity of
      the self. Autobiographical remembering and autobiographical knowledge as well as
      the stability of bodily integrity, of social roles, of significant others and of
      physical and sociocultural environment have been suggested as supporting a pre
      reflective sense of self-continuity. Stark biographical discontinuities or
      disruptions in these areas may destabilise the sense of self-continuity. To test
      the hypothesis that autobiographical reasoning in life narratives helps to
      compensate the effects of biographical discontinuities on the sense of self
      continuity, life narratives of a lifespan sample with the ages of 16, 20, 24, 28,
      44 and 69 (N = 150, 78 female) were investigated. Results confirm that if, and
      only if there have been biographical disruptions in the past four years, then
      autobiographical reasoning correlates positively with a sense of self-continuity.
      The findings contradict the thesis that mere remembering of past episodes is
      sufficient to maintain a sense of self-continuity under conditions of
      biographical change. 

PMID- 24912018
TI  - Formation and reduction of furan in maillard reaction model systems consisting of
      various sugars/amino acids/furan precursors.
AB  - To investigate the effect of the temperature on the formation of furan, various
      furan models were conducted at 90, 121, and 150  degrees C. A total 15 models,
      including alanine (ALA), serine (SER), ribose (RIB), RIB/ALA, RIB/SER, glucose
      (GLU), GLU/ALA, GLU/SER, sucrose (SUC), SUC/ALA, SUC/SER, furoic acid (FUR),
      GLU/FUR, acetaldehyde (ACET), and GLU/ACET, were prepared. The maximum level of
      furan was detected in the GLU/SER and GLU/ALA models at a molar ratio of 0.5:0.5.
      The formation of furan was proportional to the temperature in all models. The
      RIB/SER model generated the greatest amount of furan among the 11 models ranging
      from 2.1 to 4931.9 ng mL(-1) under all temperature conditions. Among the
      precursor models, the FUR model formed the greatest amount of furan ranging from
      1058.2 to 13 927.9 ng mL(-1) at all temperatures. 

PMID- 24912019
TI  - Analytic Model for the Dipole Potential of a Lipid Layer.
AB  - The larger permeability of anions than cations through a lipid bilayer can be
      rationalized by the positive sign of the bilayer's dipole potential. That is,
      upon crossing the lipid headgroups toward the hydrocarbon chain region, the
      electrostatic potential increases by several hundred millivolts. We derive an
      analytic expression for the dipole potential of a single lipid layer using an
      electrostatic model that is based on an extended version of the linearized
      Poisson-Boltzmann theory. The model highlights the ability of the lipid
      headgroups to render the dipole potential positive by inducing an orientational
      ordering of the solvent molecules. The positive contribution of the solvent
      overcompensates the negative dipole potential due to the bare lipids. Our
      theoretical prediction compares accurately with measurements of the dipole
      potential that we have conducted for mixed anionic-zwitterionic lipid monolayers
      at the air-water interface.

PMID- 24912020
TI  - Improvement in Spinal Cord Injury-Induced Bladder Fibrosis Using Mesenchymal Stem
      Cell Transplantation Into the Bladder Wall.
AB  - Experiments on spinal cord injury (SCI) have largely focused on the
      transplantation of stem cells into injured spinal cords for motor recovery while
      neglecting to investigate bladder dysfunction. The present study was performed to
      investigate the effect of B10 human mesenchymal stem cells (hMSCs) directly
      transplanted into the bladder wall of SCI rats and to determine whether they are
      capable of inhibiting collagen deposition and improving cystometric parameters in
      SCI rats. Forty 6-week-old female Sprague-Dawley rats were divided into four
      groups (group 1: control, group 2: sham operated, group 3: SCI, group 4: SCI rats
      that received B10 cells). B10 cells were labeled with fluorescent magnetic
      nanoparticles (MNPs). Four weeks after the onset of SCI, MNP-labeled B10 cells
      were injected to the bladder wall. Serial magnetic resonance (MR) images were
      taken immediately after MNP-B10 injection and at 4 weeks posttransplantation.
      Voiding function was assessed at 4 weeks posttransplantation, and the bladder was
      harvested. Improvements in bladder fibrosis and bladder function were monitored
      by molecular MR imaging. Transplantation of B10 cells into the SCI rats markedly
      reduced their weights and collagen deposition. MR images showed a clear
      hypointense signal induced by the MNP-labeled B10 cells at 4 weeks
      posttransplantation. Transplanted B10 cells were found to differentiate into
      smooth muscle cells. The intercontraction interval decreased, and the maximal
      voiding pressure increased after SCI but recovered after B10 cell
      transplantation. Survival of B10 cells was found at 4 weeks posttransplantation
      using anti-human mitochondria antibody staining and MR imaging. The transplanted
      B10 cells inhibited bladder fibrosis and ameliorated bladder dysfunction in the
      rat SCI model. MSC-based cell transplantation may be a novel therapeutic strategy
      for bladder dysfunction in patients with SCI. 

PMID- 24912021
TI  - Synthesis of triarylmethanes by palladium-catalyzed C-H/C-O coupling of oxazoles
      and diarylmethanol derivatives.
AB  - A PdCl2(MeCN)2/PPhCy2 catalyst couples oxazoles with diarylmethyl carbonates or
      pivalates to form the corresponding triarylmethanes in good yields. The catalysis
      involves successive secondary benzylic sp(3) C-O and heteroaromatic sp(2) C-H
      cleavages and provides an effective access to heteroarene-containing
      triarylmethanes from nonhalogenated and nonmetalated starting materials, which is
      complementary to precedented cross-coupling technologies with organic halides and
      organometallic reagents. 

PMID- 24912022
TI  - Chorionic villus sampling for early prenatal diagnosis: Experience at a mainland
      Chinese hospital.
AB  - The aim of this study was to describe the experience of transabdominal chorionic
      villus sampling (CVS) at a mainland Chinese hospital. During a 7-year period,
      1,172 pregnant women chose to have CVS for prenatal diagnosis. Details and
      outcome of all of these cases were reviewed. The median maternal age was 29 years
      (range 19-45). The median gestational age was 12 weeks (range 10-14). Fetal
      karyotyping and thalassaemia couples were the main indications (97.2%). Overall,
      112 (9.7%) chromosomal abnormalities were identified. There were 91 (7.8%) major
      chromosomal abnormalities, including autosomal trisomy in 70 patients, sex
      chromosomal abnormalities in 17, triploidy in two and unbalanced chromosomal
      rearrangement abnormality in two. Additionally, 137 fetuses with severe
      thalassaemia syndrome were found, including 86 homozygous beta-thalassaemia, and
      51 homozygous alpha-thalassaemia or non-deletional haemoglobin H disease. The
      procedure failed to obtain an adequate sample in four (0.3%) patients. There were
      229 pregnancies terminated for medical indications after CVS. There were three
      (0.3%) potentially procedure-related fetal losses. CVS is a safe and reliable
      prenatal diagnostic technique. It should be one of the options available to
      pregnant women who require prenatal diagnosis.

PMID- 24912023
TI  - Aqueous aerobic oxidation of alkyl arenes and alcohols catalyzed by copper(II)
      phthalocyanine supported on three-dimensional nitrogen-doped graphene at room
      temperature.
AB  - Copper(ii) tetrasulfophthalocyanine supported on three-dimensional nitrogen-doped
      graphene-based frameworks was synthesized and introduced as a bifunctional
      catalyst for selective aerobic oxidation of alkyl arenes and alcohols to the
      corresponding carbonyl compounds. The ease of catalyst separation, high turnover,
      low catalyst loading and recyclability could potentially render it applicable in
      industrial setting. 

PMID- 24912024
TI  - Prenatal exposure to manganese in South African coastal communities.
AB  - Exposure to environmental sources and altered physiological processes of
      manganese uptake during pregnancy and its possible effect on prenatal and
      postnatal development are of concern. This study investigates manganese blood
      levels at the time of delivery across four cohorts of pregnant women residing in
      coastal communities of South Africa and examines birth outcomes and environmental
      factors that could influence manganese levels in the study population. The
      geometric mean (GM) manganese blood levels (MnB) for all women at delivery was
      15.2 MUg L(-1). Collectively, rural women reported higher MnB concentrations (GM,
      16.1 MUg L(-1)) than urban women (GM, 13.5 MUg L(-1), p < 0.001). Of the 302 cord
      blood samples drawn from the study participants (rural women only), GM MnB levels
      reported for three rural sites were 25.8 MUg L(-1) (Rural 1), 33.4 MUg L(-1)
      (Rural 2) and 43.0 MUg L(-1) (Rural 3) and were twice as high as their respective
      maternal levels. However, no significant correlations were found between maternal
      and cord MnB levels across the 3 study areas. Factors associated with elevated
      maternal MnB levels, after adjusting for gestational age were: women living in a
      rural area (Rural 2) (p = 0.021); women drinking potable water from an
      outdoor/communal tap sourced from municipality (p = 0.021); drinking water from
      river/stream (p = 0.036); younger maternal age (p = 0.026); consuming leafy
      vegetables once a week (p = 0.034); and elevated maternal blood lead
      concentrations (PbB) (p = 0.002). The results indicate that MnB concentration in
      rural women during pregnancy is higher compared to urban women and increases with
      manganese intake from food and water.

PMID- 24912025
TI  - Eliciting cytotoxic T-lymphocyte responses from synthetic vectors containing one
      or two epitopes in a C57BL/6 mouse model using peptide-containing biodegradable
      microspheres and adjuvants.
AB  - We describe a vaccine delivery mechanism consisting of a synthetic, non-living
      vector of large d,l poly(lactic-co-glycolic) acid (PLGA) microspheres that carry
      specific cytotoxic T lymphocyte (CTL) epitopes. We demonstrate in mice that it
      can be used to elicit substantial interferon gamma ELISPOT responses to more than
      one specific epitope in the same individual. Our data suggest that a superior
      adjuvant configuration for the formulation is to place a TLR-9 agonist CpG inside
      the microsphere and a TLR-4 agonist MPLA in the injectate solution. This finding
      contrasts with the observations of others. Our approach provides a means to
      elicit immune responses efficiently to select epitopes, which may be important
      for an effective vaccine against HIV. 

PMID- 24912026
TI  - Vaccination of healthcare personnel: spotlight on groups with underlying
      conditions.
AB  - Healthcare personnel (HCP) are at increased risk of acquiring vaccine-preventable
      diseases (VPDs). Vaccination protects HCP and their patients from nosocomial
      transmission of VPDs. HCP who have underlying diseases (e.g., immunocompromised,
      HIV-infected, or those with chronic diseases) and HCP in particular phases of
      life (e.g., pregnant, elderly) require special consideration in regards the
      provision of vaccines. On the one hand, live virus vaccines may be
      contraindicated (e.g., pregnant HCP, immunocompromised HCP), while on the other
      hand, vaccines not routinely recommended (e.g., pneumococcal) may be indicated
      (e.g., elderly or immunocompromised HCP). It is not known how many HCP with
      underlying conditions require special consideration in the healthcare setting.
      This is an important issue, because the risk for serious morbidity, complications
      and mortality for HCP with underlying conditions will only increase. The
      prevention of nosocomial infections requires comprehensive occupational safety
      programs. The healthcare system must engage HCP and occupational physicians to
      ensure sufficient vaccination rates as part of an effective nosocomial infection
      prevention and HCP safety strategy. 

PMID- 24912027
TI  - Increased expression of Aquaporin 4 in the rat hippocampus and cortex during
      trimethyltin-induced neurodegeneration.
AB  - Trimethyltin chloride (TMT) is a neurotoxicant producing neuronal degeneration
      and reactive astrogliosis in the mammalian central nervous system, especially the
      hippocampus. A previous magnetic resonance imaging investigation in TMT-treated
      rats evidenced dilation of lateral ventricles, also suggesting alterations in
      blood-brain barrier permeability and brain edema. Aquaporin 4 (AQP4), a glial
      water channel protein expressed mainly in the nervous system, is considered a
      specific marker of vascular permeability and thought to play an important role in
      brain edema (conditions). We studied AQP4 expression in the hippocampus and
      cerebral cortex of TMT-treated rats in order to explore the molecular mechanisms
      involved in brain edema occurring in these experimental conditions. Real-time PCR
      and western blotting data showed significant up-regulation of both AQP4 mRNA and
      protein levels starting 14 days after TMT treatment in the hippocampus and
      cortex. Parallel immunofluorescence studies indicated intense astrogliosis and
      AQP4 immunoreactivity diffusely pronounced in the hippocampal and cortex areas
      starting 14 days after TMT intoxication. In order to study the effects of TMT on
      vascular integrity, double-label immunofluorescence experiments for rat
      immunoglobulin G (IgG) and rat endothelial cell antigen-1 (RECA-1) or neuronal
      nuclei (NeuN) (endothelial and neuronal markers respectively) were performed. The
      results indicated, at 21 and 35 days after treatment, the presence of rat IgG in
      paravasal parenchyma and in some neuronal cells of the hippocampus and cortex.
      The extravasated IgG staining was temporally correlated with over-expression of
      neuronal vascular endothelial growth factor (VEGF) and the active phosphorylated
      form of its neuronal receptor (VEGFR-2P), suggesting that these factors may
      cooperate in mediating vascular leakage.

PMID- 24912028
TI  - Late enhancement of brain-behavior correlations during response inhibition.
AB  - Previous neuroimaging studies of response inhibition have examined correlations
      between behavioral efficiency and brain activity, but the temporal stability of
      the correlations has largely been ignored. The present functional magnetic
      resonance imaging (fMRI) study demonstrates the temporal changes of the brain
      activity associated with performance efficiency that led to more robust brain
      behavior correlations in a later part of the experimental sessions. Participants
      performed a stop-signal task requiring inhibition of inappropriate responses,
      where more efficient behavioral performance is reflected in a shorter stop-signal
      reaction time (SSRT). Among across-subject negative correlations between the
      brain activity and the SSRT, the majority of the negative correlations were
      observed in the second half of experimental sessions. In the cerebellar region
      that showed the greatest difference in correlations between the second and the
      first halves, the brain activity increased in efficient performers, whereas the
      brain activity decreased in poor performers. These results suggest the existence
      of multiple brain mechanisms that increase and decrease the brain activity
      depending on the behavioral efficiency of the performers. More practically, these
      results indicate that robust brain-behavior correlations can more effectively be
      detected in a later part of the experimental sessions. 

PMID- 24912029
TI  - The common antitussive agent dextromethorphan protects against hyperoxia-induced
      cell death in established in vivo and in vitro models of neonatal brain injury.
AB  - Preterm infants are prematurely subjected to relatively high oxygen
      concentrations, even when supplemental oxygen is not administered. There is
      increasing evidence to show that an excess of oxygen is toxic to the developing
      brain. Dextromethorphan (DM), a frequently used antitussive agent with
      pleiotropic mechanisms of action, has been shown to be neuroprotective in various
      models of central nervous system pathology. Due to its numerous beneficial
      properties, it might also be able to counteract detrimental effects of a neonatal
      oxygen insult. The aim of the current study was to evaluate its therapeutic
      potential in established cell culture and rodent models of hyperoxia-induced
      neonatal brain injury. For in vitro studies pre- and immature oligodendroglial
      (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre
      treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat
      pups received a single intraperitoneal injection of DM in two different dosages
      prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3
      activation were assessed as outcome parameters at the end of exposure. DM
      significantly increased cell viability in immature oligodendroglial cells
      subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not
      significantly affected by DM treatment. In vivo caspase-3 activation induced by
      hyperoxic exposure was significantly lower after administration of DM in gray and
      white matter areas. In control animals kept under normoxic conditions DM did not
      significantly influence caspase-3-dependent apoptosis. The present results
      indicate that DM is a promising and safe treatment strategy for neonatal
      hyperoxia-induced brain injury that merits further investigation.

PMID- 24912030
TI  - Calculation of the volumetric characteristics of biomacromolecules in solution by
      the Voronoi-Delaunay technique.
AB  - Recently a simple formalism was proposed for a quantitative analysis of
      interatomic voids inside a solute molecule and in the surrounding solvent. It is
      based on the Voronoi-Delaunay tessellation of structures, obtained in molecular
      simulations: successive Voronoi shells are constructed, starting from the
      interface between the solute molecule and the solvent, and continuing to the
      outside (into the solvent) as well as into the interior of the molecule.
      Similarly, successive Delaunay shells, consisting of Delaunay simplexes, can also
      be constructed. This technique can be applied to interpret volumetric data,
      obtained, for example, in studies of proteins in aqueous solution. In particular,
      it allows replacing qualitatively and descriptively introduced properties by
      strictly defined quantities, such as the thermal volume, by the boundary voids.
      The extension and the temperature behavior of the boundary region, its structure
      and composition are discussed in detail, using the example of a molecular
      dynamics model of an aqueous solution of the human amyloid polypeptide, hIAPP. We
      show that the impact of the solute on the local density of the solvent is short
      ranged, limited to the first Delaunay and the first Voronoi shell around the
      solute. The extra void volume, created in the boundary region between solute and
      solvent, determines the magnitude and the temperature dependence of the apparent
      volume of the solute molecule. 

PMID- 24912031
TI  - Sensory-motor performance after acute glutathione depletion by L-buthionine
      sulfoximine injection into substantia nigra pars compacta.
AB  - Glutathione is the major antioxidant in the living cells. Its deficit has been
      linked to neurodegenerative disorders as Parkinson's disease but its role in the
      etiology of nigral degeneration and sensory-motor performance has been poorly
      explored. To evaluate the effect of glutathione depletion on nigro-striatal
      oxidative metabolism and sensory-motor performance in rats, l-buthionine
      sulfoximine (15 mM) or saline solution was injected into substantia nigra pars
      compacta (SNpc). Then, oxidative metabolism was studied 24h and 7 days later in
      SNpc and corpus striatum (CS). Tyrosine hydroxylase and GFAP immunohistochemistry
      assays were carried out at 7 days. In addition, animals were evaluated in open
      field, adhesive removal, staircase and traverse beam tests. Glutathione depletion
      induced compensatory response in catalase activity and glial response in the in
      SNpc and no oxidative damage was observed. However, a loss in dopaminergic cells
      was found. At the same time, animals with glutathione depletion have shown poor
      performance in behavioral tests except for staircase test. These results suggest
      that glutathione depletion can be related to sensory-motor dysfunction.

PMID- 24912032
TI  - Nanostructuring of hierarchical 3D cystine flowers for high-performance
      electrochemical immunosensor.
AB  - Here, we report a simple and reproducible method for large scale fabrication of
      novel flower and palm-leaf like 3D cystine microstructures (CMs) with high
      uniformity having a size of 50 um and 10 um respectively, through a facile
      aqueous solution route as a function of pH and concentration. In a proof-of
      concept study, the 3D CMs have been further explored to fabricate a label-free
      high-performance electrochemical immunosensor by immobilizing monoclonal
      antibodies. Electrochemical methods were employed to study the stepwise
      modification of the system and the electronic transduction for the detection. The
      fabricated immunosensor design demonstrates high performance with enhanced
      sensitivity (4.70 cfu ml(-1)) and linear sensing range from 10 to 3 x 10(9) cfu
      ml(-1) a long shelf-life (35 days) and high selectivity over other bacterial
      pathogens. The enhanced performance originates from a novel nanostructuring in
      which the CMs provide higher surface coverage for the immobilization of
      antibodies providing excellent electronic/ionic conductivity which result in the
      enhanced sensitivity.

PMID- 24912033
TI  - Gold nanoparticles conjugates-amplified aptamer immunosensing screen-printed
      carbon electrode strips for thrombin detection.
AB  - Thrombin plays the role in cardiovascular diseases and regulates many processes
      in inflammation and could be a feature of many pathological conditions, including
      the thromboembolic disease, cancer and neurodegenerative diseases. An
      ultrasensitive and amplified electrochemical sandwich assay using screen-printed
      carbon electrode (SPCE) strips for thrombin detection was established in this
      study. The conductivity and sensing performance of the carbon electrodes were
      enhanced by using gold nanoparticles (AuNPs). The aptamer addressed on the strips
      was used as a primary probe to capture thrombin in the detected samples. An
      amplifier was invented for recognizing thrombin captured on the SPCE, which is
      the multiple molecules of anti-thrombin antibody (Ab) and horseradish peroxidase
      (HRP) co-modified AuNPs (AuNPs/Ab-HRP). Hydrogen peroxide was used as the
      substrate for HRP and then the response current (RC) could be detected. The
      optimization of these AuNPs conjugates-amplified aptamer immunosensing SPCE
      strips was conducted for thrombin detection. The detection sensitivity showed a
      linear relation between RC and thrombin concentration in the range of 10 pM-100
      nM, and limit of detection (LOD) was 1.5 pM. The fabricated AuNPs/Ab-HRP
      amplified aptamer immunosensing SPCE strips were further used to detect thrombin
      in human serum with a linear range of 100 pM-100 nM. This study provided the
      promising SPCE strips with highly sensitive and rapid detection for thrombin by
      the electrochemical aptasensor combined with AuNPs conjugates for amplifying the
      detection signal.

PMID- 24912034
TI  - Using "dioscorea batatas bean"-like silver nanoparticles based localized surface
      plasmon resonance to enhance the fluorescent signal of zinc oxide quantum dots in
      a DNA sensor.
AB  - We reported here the preparation of "dioscorea batatas bean"-like silver
      nanoparticles (AgNPs) and the unique structure provided the AgNPs good localized
      surface plasmon resonance (LSPR) property. In addition, zinc oxide quantum dots
      (ZnO QDs) were also synthesized and found with good fluorescent property.
      Furthermore, the ZnO QDs decorated exfoliated graphene oxide (EGO-ZnO) was
      prepared via electrostatic interaction. The named nanomaterials were applied in a
      LSPR-induced fluorescent DNA sensor. To fabricate the DNA sensor, the EGO-ZnO was
      modified on the silica glass as the supporter for the capture probe ssDNA, and
      the complementary ssDNA was labeled on the surface of the AgNPs. After the
      hybridization step by step, the AgNPs was fastened on the surface of the EGO-ZnO,
      and the fluorescent intensity of the EGO-ZnO increased as a result. The prepared
      DNA sensor enabled the target ssDNA to be detected in the concentration range of
      10(-19)-10(-14)M, and the limit of detection was 4.3 * 10(-20)M.

PMID- 24912035
TI  - Ultrasensitive fluorescence detection of nucleic acids using exonuclease III
      induced cascade two-stage isothermal amplification-mediated zinc (II)
      protoporphyrin IX/G-quadruplex supramolecular fluorescent nanotags.
AB  - A cascadic sensing system was developed for detection of DNA target at ultralow
      concentration by a combination of magnetic nanoparticles (MNPs) and exonuclease
      III (Exo III)-induced cascade two-stage isothermal amplification in the study. An
      ingeniously designed capture hairpin probe (CHP) that integrates target-binding
      and signal transduction sequences within one multifunctional design was assembled
      on MNPs. Upon sensing of the analyte nucleic acid, the hairpin probe on MNPs
      could be opened and stepwise removed by Exo III accompanied by the releasing of
      target DNA for the successive hybridization and cleavage process and the
      generation of bare signal transduction sequences of CHP as a new trigger for next
      circular reaction. The new DNA triggers initiate hybridizing with hairpin DNA
      probe that contains a partially "caged" G-quadruplex sequence (GHP), forming a
      duplex structure and liberating the active G-quadruplex structure. Then, Exo III
      digests the resulting duplex domain, leading to the recycling of new DNA trigger
      and simultaneously generating numerous ZnPPIX/G-quadruplex supramolecular
      complexes with the help of the zinc (II)-protoporphyrin IX (ZnPPIX), as an
      optical label for amplified fluorescence sensing event. Finally, numerous
      liberated cascade ZnPPIX/G-quadruplex supramolecular complexes give a remarkable
      fluorescence response. Because of two-stage autocatalytic recycling amplification
      and the specifically catalyzed formation of ZnPPIX/G-quadruplex supramolecular
      complexes, this newly designed protocol provides a high sensitivity with a
      detection limit of 0.75 fM, can discriminate mismatched DNA from perfectly
      matched target DNA, and gives low matrix effect due to using MNPs as the
      separation and amplification elements in the real samples. Therefore, it holds
      great potential for early diagnosis in gene-related diseases. 

PMID- 24912036
TI  - Sensing strategies for influenza surveillance.
AB  - Influenza viruses, which are RNA viruses belonging to the family
      Orthomyxoviridae, cause respiratory diseases in birds and mammals. With seasonal
      epidemics, influenza spreads all over the world, resulting in pandemics that
      cause millions of deaths. Emergence of various types and subtypes of influenza,
      such as H1N1 and H7N9, requires effective surveillance to prevent their spread
      and to develop appropriate anti-influenza vaccines. Diagnostic probes such as
      glycans, aptamers, and antibodies now allow discrimination among the influenza
      strains, including new subtypes. Several sensors have been developed based on
      these probes, efforts made to augment influenza detection. Herein, we review the
      currently available sensing strategies to detect influenza viruses. 

PMID- 24912037
TI  - A dual-signal amplification method for the DNA detection based on exonuclease
      III.
AB  - A dual-signal amplification method based on two molecular beacons was designed
      for human hemochromatosis (HFE) gene detection. The two probes, P1 and P2, could
      resist the exonuclease III (Exo III) digestion due to the 3'-termini protrusion,
      and could coexist stably with Exo III. In the presence of HFE targets, P1
      hybridized with a HFE target to form a duplex DNA with a recessed 3'-hydroxyl
      termini and then partially digested by Exo III, releasing the HFE target and a
      residual sequence (X). This X sequence could trigger the digestion of P2 probes
      with 6-carboxy-fluoresceins and Black Hole Quenchers and then result in the
      increase of fluorescence intensity. The X sequences were more stable than HFE
      targets and could cyclically trigger the P2 digestion for a long time even though
      the HFE targets were digested by Exo III. This method improved the sensitivity
      and reached 4 orders of magnitude in detection limit, and showed excellent
      selectivity to discriminate single base mismatched targets well. 

PMID- 24912039
TI  - Layer-by-layer assembled multilayer films of exfoliated layered double hydroxide
      and carboxymethyl-beta-cyclodextrin for selective capacitive sensing of
      acephatemet.
AB  - Novel organic-inorganic hybrid ultrathin films were fabricated by alternate
      assembly of cationic exfoliated Mg-Al-layered double hydroxide (LDH) nanosheets
      and carboxymethyl-beta-cyclodextrin (CMCD) as a polyanion onto a glassy carbon
      electrode (GCE) via a layer-by-layer (LBL) approach. The multilayer films were
      then characterized by means of X-ray powder diffraction (XRD), infrared
      spectroscopy (IR), and scanning electron microscopy (SEM). These films were found
      to possess a long range stacking order in the normal direction of the substrate
      with a continuous and uniform morphology. Its electrochemical performance was
      systematically investigated. Our results demonstrate that such a newly designed
      (LDH/CMCD)n multilayer film, combining the individual properties of CMCD (a high
      supramolecule recognition and enrichment capability) together with LDH nanosheets
      (a rigid inorganic matrix), can be applied to a sensitive, simple, and label-free
      capacitive detection of acephatemet (AM). Molecular docking calculations further
      disclose that the selective sensing behavior toward AM may be attributed to the
      specific binding ability of CMCD to AM. Under the optimized conditions, the
      capacitive change of AM was proportional to its concentration ranging from 0.001
      to 0.10 MUg mL(-1) and 0.1 to 0.8 MUg mL(-1) with a detection limit 0.6 ng mL(-1)
      (S/N=3). Toward the goal for practical applications, this simple probe was
      further evaluated by monitoring AM in real samples.

PMID- 24912038
TI  - Fluorescent hydrogen peroxide sensor based on cupric oxide nanoparticles and its
      application for glucose and L-lactate detection.
AB  - A novel fluorescent hydrogen peroxide sensor was developed based on the
      peroxidase-like activity of cupric oxide nanoparticles. Cupric oxide
      nanoparticles effectively catalyzed the decomposition of hydrogen peroxide into
      hydroxyl radicals. Then terephthalic acid was oxidized by hydroxyl radical to
      form a highly fluorescent product. The linear range of hydrogen peroxide
      estimated to be 5.0 * 10(-6)-2.0 * 10(-4)M with a detection limit of 3.4 * 10(
      7)M. Moreover, this detection system enabled the sensing of analytes which can
      enzymatically generate hydrogen peroxide. By coupling the oxidation of glucose or
      L-lactate catalyzed by their corresponding oxidase enzymes with terephthalic acid
      oxidation catalyzed by cupric oxide nanoparticles, sensitive assays of glucose
      and l-lactate with detection limits of 1.0 * 10(-6) and 4.5 * 10(-8)M were
      realized. The successful applications of this approach in human serum samples
      have also been demonstrated.

PMID- 24912040
TI  - "Chemical nose" for the visual identification of emerging ocular pathogens using
      gold nanostars.
AB  - Ocular pathogens can cause serious damages in the eye leading to severe vision
      loss and even blindness if left untreated. Identification of pathogens is crucial
      for administering the appropriate antibiotics in order to gain effective control
      over ocular infection. Herein, we report a gold nanostar based "chemical nose"
      for visually identifying ocular pathogens. Using a spectrophotometer and
      nanostars of different sizes and degrees of branching, we show that the "chemical
      nose" is capable of identifying the following clinically relevant ocular
      pathogens with an accuracy of 99%: S. aureus, A. xylosoxidans, D. acidovorans and
      S. maltophilia. The differential colorimetric response is due to electrostatic
      aggregation of cationic gold nanostars around bacteria without the use of
      biomolecule ligands such as aptamers or antibodies. Transmission electron
      microscopy confirms that the number of gold nanostars aggregated around each
      bacterium correlates closely with the colorimetric response. Thus, gold nanostars
      serve as a promising platform for rapid visual identification of ocular pathogens
      with application in point-of-care diagnostics. 

PMID- 24912041
TI  - An ionic liquid-modified graphene based molecular imprinting electrochemical
      sensor for sensitive detection of bovine hemoglobin.
AB  - A novel kind of molecular imprinted polymers based on ionic liquid-functionalized
      graphene (MIPs/IL/GR) was prepared by electro-polymerization, which was applied
      as a molecular recognition element to modify glassy carbon electrode (GCE) to
      construct an electrochemical sensor (MIPs/IL/GR/GCE) for sensitive detection of
      bovine hemoglobin (BHb). The fabrication conditions that affect the performance
      of the imprinted sensor, such as pyrrole concentration, scan cycles and scan
      rates, have been discussed. Under the optimized conditions, the prepared
      molecular imprinting electrochemical sensor showed a fast rebinding dynamics,
      which was successfully applied to BHb detection with a wide linear range from 1.0
      * 10(-10) to 1.0 * 10(-3)g/L (R=0.998) and a detection limit of 3.09 * 10(
      11)g/L. Moreover, the fabricated sensor possessed a good selectivity and
      stability, providing a promising tool for immunoassays and clinical applications.

PMID- 24912042
TI  - Relationship between oral problems and Helicobacter pylori infection.
AB  - OBJECTIVE: The aim of this study is to investigate the relationship between oral
      problems and Helicobacter pylori (Hp) infection, and to reveal which oral
      problems are significantly related with Hp infection. METHODS: Participants
      undergoing healthy medical examination were examined for 12 kinds of oral
      problems: dental calculus, oral mucosal disease, periodontal disease, decayed
      tooth, tooth defect, disuse tooth, residual crown and root, devital tooth, loose
      tooth, fistula, ill-fitting fixed denture and ectopic tooth. Hp infection was
      confirmed by (13)C-urea breath test. Participant information including age,
      educational level, smoking habits, drinking habits, height, weight and body mass
      index (BMI) were collected using a standard questionnaire. RESULTS: Hp infection
      was 46.97% of the 54,036 cases. Age (P<0.01), gender (P<0.001) and BMI (P<0.01)
      were significantly associated with Hp infection. Smoking (P<0.001) and regular
      drinking (P<0.001) were showed to be associated with Hp infection. After
      adjustments for other associated factors, in all of the 12 oral problems, only
      dental calculus [n=35,559, OR (95% CI)=1.05 (1.01-1.09), P=0.012] and loose tooth
      [n=2411, OR (95% CI)=1.22 (1.03-1.22), P=0.007] were related with Hp infection.
      CONCLUSION: In a cross-sectional analysis, the prevalence of Hp infection was
      strongly related with several social problems, including age, gender, BMI,
      smoking and regular drinking. In addition, oral problems, particularly dental
      calculus and loose tooth, were found to be associated with Hp infection, possibly
      due to the dental plaque. The study suggested that to prevent or eradicate Hp
      infection, we need to focus on oral hygiene and prevention of oral problems,
      especially dental calculus and loose tooth.

PMID- 24912043
TI  - Evapotranspiration of tropical peat swamp forests.
AB  - In Southeast Asia, peatland is widely distributed and has accumulated a massive
      amount of soil carbon, coexisting with peat swamp forest (PSF). The peatland,
      however, has been rapidly degraded by deforestation, fires, and drainage for the
      last two decades. Such disturbances change hydrological conditions, typically
      groundwater level (GWL), and accelerate oxidative peat decomposition.
      Evapotranspiration (ET) is a major determinant of GWL, whereas information on the
      ET of PSF is limited. Therefore, we measured ET using the eddy covariance
      technique for 4-6 years between 2002 and 2009, including El Nino and La Nina
      events, at three sites in Central Kalimantan, Indonesia. The sites were different
      in disturbance degree: a PSF with little drainage (UF), a heavily drained PSF
      (DF), and a drained burnt ex-PSF (DB); GWL was significantly lowered at DF,
      especially in the dry season. The ET showed a clear seasonal variation with a
      peak in the mid-dry season and a large decrease in the late dry season, mainly
      following seasonal variation in net radiation (Rn ). The Rn drastically decreased
      with dense smoke from peat fires in the late dry season. Annual ET forced to
      close energy balance for 4 years was 1636 +/- 53, 1553 +/- 117, and 1374 +/- 75
      mm yr(-1) (mean +/- 1 standard deviation), respectively, at UF, DF, and DB. The
      undrained PSF (UF) had high and rather stable annual ET, independently of El Nino
      and La Nina events, in comparison with other tropical rainforests. The minimum
      monthly-mean GWL explained 80% of interannual variation in ET for the forest
      sites (UF and DF); the positive relationship between ET and GWL indicates that
      drainage by a canal decreased ET at DF through lowering GWL. In addition, ET was
      decreased by 16% at DB in comparison with UF chiefly because of vegetation loss
      through fires.

PMID- 24912044
TI  - Molecular composition and biodegradability of soil organic matter: a case study
      comparing two new England forest types.
AB  - Soil organic matter (SOM) is involved in many important soil processes such as
      carbon sequestration and the solubility of plant nutrients and metals. Ultrahigh
      resolution mass spectrometry was used to determine the influence of forest
      vegetation type and soil depth on the molecular composition of the water
      extractable organic matter (WEOM) fraction. Contrasting the upper 0-5 cm with the
      25-50 cm B horizon depth increment, the relative abundance of lipids and
      carbohydrates significantly increased, whereas condensed aromatics and tannins
      significantly decreased for the deciduous stand WEOM. No significant abundance
      changes were found for the coniferous stand DOM. Kendrick mass defect analysis
      showed that the WEOM of the 25-50 cm B horizon was depleted in oxygen-rich and
      higher mass components as compared to the 0-5 cm B horizon WEOM, suggesting that
      higher mass WEOM components with oxygen-containing functionality show greater
      reactivity in abiotic and/or biotic reactions. Furthermore, using an inoculated
      14-day laboratory incubation study and multivariate ordination methods, we
      identified the WEOM components with H:C > 1.2 and O:C > 0.5 as being correlated
      most strongly with biodegradability. Our findings highlight the importance of
      understanding soil depth differences for various forest types in the chemical
      composition of SOM and the processes governing SOM production and transformations
      to fully understand the ecological implications of changes in forest composition
      and function in a changing climate. 

PMID- 24912045
TI  - Analysis of gastrin-releasing peptide gene and gastrin-releasing peptide receptor
      gene in patients with agoraphobia.
AB  - A gastrin-releasing peptide receptor (GRPR) knock-out mouse model provided
      evidence that the gastrin-releasing peptide (GRP) and its neural circuitry
      operate as a negative feedback-loop regulating fear, suggesting a novel candidate
      mechanism contributing to individual differences in fear-conditioning and
      associated psychiatric disorders such as agoraphobia with/without panic disorder.
      Studies in humans, however, provided inconclusive evidence on the association of
      GRP and GRPR variations in agoraphobia with/without panic disorder. Based on
      these findings, we investigated whether GRP and GRPR variants are associated with
      agoraphobia. Mental disorders were assessed via the Munich-Composite
      International Diagnostic Interview (M-CIDI) in 95 patients with agoraphobia
      with/without panic disorder and 119 controls without any mental disorders. A
      complete sequence analysis of GRP and GRPR was performed in all participants. We
      found no association of 16 GRP and 7 GRPR variants with agoraphobia with/without
      panic disorder. 

PMID- 24912046
TI  - No association of Val158Met variant in the COMT gene with autism spectrum
      disorder in Thai children.

PMID- 24912047
TI  - Summaries of oral sessions at the XXI World Congress of Psychiatric Genetics,
      Boston, Massachusetts, 17-21 October 2013: state of the field.
AB  - The XXI World Congress of Psychiatric Genetics (WCPG), sponsored by the
      International Society of Psychiatric Genetics (ISPG), took place in Boston,
      Massachusetts, on 17-21 October 2013. Approximately 900 participants gathered to
      discuss the latest findings in this rapidly advancing field. The following report
      was written by student travel awardees. Each was assigned one or more sessions as
      a rapporteur. This manuscript represents topics covered in most, but not all of
      the oral presentations during the conference, and contains some of the major
      notable new findings reported. 

PMID- 24912049
TI  - WITHDRAWN: Newborn screening for lysosomal disordersby tandem mass spectrometry.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24912048
TI  - Pharmacogenetics of chronic pain management.
AB  - OBJECTIVE: The experience of chronic pain is one of the commonest reasons
      individuals seek medical attention, making the management of chronic pain a major
      issue in clinical practice. Drug metabolism and responses are affected by many
      factors, with genetic variations offering only a partial explanation of an
      individual's response. There is a paucity of evidence for the benefits of
      pharmacogenetic testing in the context of pain management. DESIGN AND METHODS: We
      reviewed the literature between 2000 and 2013, and references cited therein,
      using various keywords related to pain management, pharmacology and
      pharmacogenetics. RESULTS: Opioids continue to be the mainstay of chronic pain
      management. Several non-opioid based therapies, such as treatment with
      cannabinoids, gene therapy and epigenetic-based approaches are now available for
      these patients. Adjuvant therapies with antidepressants, benzodiazepines or
      anticonvulsants can also be useful in managing pain. Currently, laboratory
      monitoring of pain management patients, if performed, is largely through urine
      drug measurements. CONCLUSIONS: Drug half-life calculations can be used as
      functional markers of the cumulative effect of pharmacogenetics and drug-drug
      interactions. Assessment of half-life and therapeutic effects may be more useful
      than genetic testing in preventing adverse drug reactions to pain medications,
      while ensuring effective analgesia. Definitive, mass spectrometry-based methods,
      capable of measuring parent drug and metabolite levels, are the most useful
      assays for this purpose. Urine drug measurements do not necessarily correlate
      with serum drug concentrations or therapeutic effects. Therefore, they are
      limited in their use in monitoring efficacy and toxicity.

PMID- 24912051
TI  - Structure evolution of poly(3-hexylthiophene) on Si wafer and poly(vinylphenol)
      sublayer.
AB  - The structure evolution of P3HT thin films on Si wafer and PVPh covered Si wafer
      during heating, thermal annealing, and melt recrystallization processes has been
      studied in detail using X-ray analysis techniques. The effect of substrate on the
      crystallization behavior and interface structure of P3HT films was explored. For
      the P3HT films deposited on the Si substrate, it was found that the stability of
      P3HT crystals is orientation dependent. The crystals oriented with b-axis normal
      to the substrate, that is, a face-on molecular orientation, are less stable than
      those with the a-axis arranged normal to the substrate (side-on molecular
      orientation). Thermal annealing temperature plays an important role in the
      molecular structure of P3HT including crystal structure, film thickness, and
      surface roughness. After annealing at relatively high temperature, new crystals
      form during the cooling process accompanied by the shrinking of a-axis. Moreover,
      the melt recrystallization favors the formation of more stable P3HT crystals with
      side-on molecular orientation. The PVPh substrate does not affect the
      crystallization behavior of solution cast P3HT significantly but inhibits the
      formation of P3HT crystal with face-on molecular orientation. However, the
      interfacial morphology of P3HT and PVPh changes by annealing at elevated
      temperature. The P3HT/PVPh interface changes from a sharply defined one into a
      diffused one at around 160  degrees C. The PVPh sublayer inhibits the melt
      recrystallization of P3HT to some extent, leading to a slight expansion of the a
      axis. 

PMID- 24912050
TI  - Recent advances in head and neck squamous cell carcinoma--a review.
AB  - The current review presents the results of the most recent studies performed on
      different aspects of human head and neck squamous cell carcinoma, including
      radiosensitivity induction, efficiency improvement of monoclonal antibodies using
      low-intensity ultrasound, chemical compounds such as toll-like receptor (TLC)
      agonists, dasatinib, resveratrol and niclosamide, nuclear inhibition of cancer
      using STAT3 decoy oligonucleotide, efficiency of anti-EGFR monoclonal antibodies
      in detection of head and neck cancers and other related issues. 

PMID- 24912052
TI  - Reliability of self-reporting of antibiotic consumption in the community - Index
      of Reliability.
AB  - WHAT IS KNOWN AND OBJECTIVE: To date, there is no evidence to indicate the
      reliability of how patients self-report their own antibiotic usage in the
      community. Such data are fundamental in supporting antimicrobial stewardship
      practices, and so there is a need to determine its accuracy and reliability.
      COMMENT: Patients in the community (n = 476) were required to recollect their
      antibiotic usage in the past three months. Simultaneously, similar information
      was obtained by careful extraction from their respective medical notes, which was
      qualitatively compared with the patient's recollection. Overall, concordance was
      high (88.1%), but age (<20 and >80 years) and sex (female) were significant
      factors of reliability. WHAT IS NEW AND CONCLUSION: This study suggests that
      basic self-reporting of antibiotic usage amongst patients is relatively reliable,
      with increasing accuracy with years until 80 years. Where such information is
      critical, the current study can help decide who to interview and whose notes to
      interrogate, in the quest to obtain reliable and accurate information.

PMID- 24912053
TI  - Addition of strawberries to the usual diet decreases resting chemiluminescence of
      fasting blood in healthy subjects-possible health-promoting effect of these
      fruits consumption.
AB  - OBJECTIVE: Regular strawberry consumption augmented plasma antioxidant activity
      and decreased lipid peroxidation suggests preventive potential of these fruits
      against oxidative stress-dependent disorders. Blood phagocytes are important
      source of oxidants that may contribute to systemic oxidative stress. We examined
      the effect of strawberry consumption on the luminol enhanced whole blood
      chemiluminescence (LBCL) reflecting oxidants generation by circulating phagocytes
      in healthy subjects. METHODS: Thirty-one healthy subjects (being on their usual
      diet) consumed 500 g of strawberry pulp daily (between 11.00-14.00) for 30 days
      (1st strawberry course) and after 10 day wash-out the cycle was repeated (2nd
      strawberry course). Fasting blood and spot morning urine samples were collected
      before and after each strawberry course for measuring resting and agonist (fMLP)
      induced LBCL, various phenolics and plasma antioxidant activity. Twenty subjects
      served as a control in respect to LBCL changes over the study period. RESULTS:
      Strawberry consumption decreased median resting LBCL and this effect was more
      evident after the 1st course (by 38.2%, p < 0.05) than after the the 2nd one
      (18.7%), while fMLP-induced LBCL was constant. No changes in LBCL were noted in
      controls. Strawberries increased fasting plasma levels of caffeic acid and
      homovanillic acid as well as urolithin A and 4-hydroxyhippuric acid in spot
      urine. Plasma antioxidant activity and the number of circulating phagocytes did
      not change over the study period. Resting LBCL correlated positively with the
      number of circulating polymorphonuclear leukocytes at all occasions and negative
      correlation with plasma 4-hydroxyhippuric acid was noted especially after the
      first strawberry course (r = -0.46, p < 0.05). CONCLUSIONS: The decrease in
      resting LBCL suggests that regular strawberry consumption may suppress baseline
      formation of oxidants by circulating phagocytes. This may decrease the risk of
      systemic imbalance between oxidants and anti-oxidants and be one of mechanisms of
      health-promoting effect of these fruits consumption.

PMID- 24912054
TI  - Restricting interactions with industry to promote evidence-based prescribing.

PMID- 24912055
TI  - Recovery from first-episode psychosis and recovering self: A qualitative study.
AB  - OBJECTIVE: The objective of this study was to explore the subjective factors
      associated with the experience of first-episode psychosis (FEP) and the very
      first stages of recovery to develop our understanding of this process and improve
      treatment outcomes. METHOD: Interpretive Phenomenological Analysis was used to
      explore the experiences of 20 young people who had recently experienced FEP.
      RESULTS: Two broad superordinate themes captured essential thematic trends in the
      data: experiences of self-estrangement and self-consolidation. The concept of
      dialogical self was used to understand the effect of psychosis on self and the
      process of resuming familiar social positions to facilitate recovery. The concept
      of making meaning after traumatic events was also applied to the narratives of
      personal growth that participants formed. Those who reported subjective
      improvements in recovery were more likely to have developed a meaningful
      interpretation of their psychosis, strengthened relationships with others, and
      forged a stronger sense of self. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The
      experience of self-consolidation was strongly associated with the person's
      resumption of familiar social roles and their ability to make meaning from their
      experience in a way that promoted personal growth. Although these processes are
      known to be part of personal recovery, this study highlights their importance in
      the very early stages of recovery immediately after the experience of FEP.

PMID- 24912056
TI  - A national campaign to finance supported employment.
AB  - Medicaid is now the main payment source and financing mechanism for services for
      adults with serious mental illness. Services formerly paid with state mental
      health funds have been converted to Medicaid, lightening the burden on state
      budgets affected by recession and other factors. The change has allowed states to
      maintain community care and inpatient services (in general hospitals). Medicaid
      service benefits include clinic and inpatient care, case management, and some
      rehabilitation services. But using Medicaid to finance some high-priority
      services such as supported employment has proven difficult. Now critical changes
      in Medicaid under the Affordable Care Act allow states to amend their Medicaid
      State Plans to provide more flexible services to people with serious mental
      illness. Advocacy and support may be needed to encourage this step. A national
      campaign to finance supported employment would join various stakeholders in the
      field, including professional organizations, family and service user groups, and
      organizations representing service providers. The authors of this editorial
      pledge their energies to support this campaign. They present suggestions for a
      campaign, including building a coalition, goals and targets, and online
      resources.

PMID- 24912057
TI  - Introduction to the special issue on individual placement and support.
AB  - This issue of the Psychiatric Rehabilitation Journal presents an update on
      individual placement and support (IPS), the evidence-based practice of supported
      employment for people with psychiatric disabilities. The papers in this special
      issue testify to the enormous potential of the IPS model. Clients, families,
      researchers, policy experts, practitioners, and administrators continue to
      identify creative ways to expand services to reach more people. The state of the
      art of IPS is expanding, changing, and ramifying broadly. IPS is appearing in
      middle-income countries in Latin America and in new populations, such as young
      adults with autism-spectrum disorders in Europe. Continued growth should follow
      the fundamental principles of values and science. First, we must honor basic
      values by listening to and learning from clients (Strickler, 2014), as well from
      IPS trainers, mental health and vocational rehabilitation leaders, and
      practitioners who face the daily realities of developing and sustaining recovery
      oriented services (Swanson et al., 2014). Second, we must insist on rigorous
      research to ground our employment services in hard evidence.

PMID- 24912058
TI  - The potential of technology for enhancing individual placement and support
      supported employment.
AB  - TOPIC: The potential of technology to enhance delivery and outcomes of Individual
      Placement and Support (IPS) supported employment. PURPOSE: IPS supported
      employment has demonstrated robust success for improving rates of competitive
      employment among individuals with psychiatric disabilities. Still, a majority of
      those with serious mental illnesses are not employed (Bond, Drake, & Becker,
      2012). The need to promote awareness of IPS and expand services is urgent. In
      this study, we describe ways that technologies may enhance delivery of IPS
      supported employment across the care continuum and stakeholder groups. Directions
      for research are highlighted. SOURCES USED: published literature, clinical
      observations, IPS learning collaborative. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Technology has the potential to enhance direct service as well as
      workflow in the IPS supported employment process, which may lead to improved
      fidelity and client outcomes. Mobile and cloud technologies open opportunities
      for collaboration, self-directed care, and ongoing support to help clients obtain
      and maintain meaningful employment. Research is needed to evaluate efficacy of
      technology-based approaches for promoting client employment outcomes, to identify
      provider and organization barriers to using technology for IPS delivery, and to
      determine effective strategies for implementing technology with IPS in different
      settings and with diverse client audiences.

PMID- 24912059
TI  - Individual placement and support (IPS) in physical rehabilitation and medicine:
      the VA spinal cord injury experience.
AB  - TOPIC: This report summarizes the first studies on individual placement and
      support (IPS) in the field of physical medicine and rehabilitation (PM&R) and
      discusses adaptation of the model. PURPOSE: Research related to the
      implementation and evaluation of the use of IPS in the VA System of Spinal Cord
      Injury Care is reviewed. Results suggest that IPS was more effective than
      traditional vocational rehabilitation. With physical disabilities, the model
      needs adaptation with respect to integration, disclosure, and job development
      while following the core principles. Special consideration is needed with respect
      to caseload size and transportation issues. SOURCES USED: Published results from
      the Spinal Cord Injury Vocational Integration Program (SCI-VIP) study and
      clinical field observations. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: IPS can
      be successfully adapted to physical medicine and rehabilitation.

PMID- 24912060
TI  - The effects of supported employment in Latino consumers with severe mental
      illness.
AB  - OBJECTIVE: Despite the large number of Latinos living in the United States,
      little research has evaluated the effectiveness of different vocational
      rehabilitation programs for individuals with severe mental illness in this
      rapidly growing minority population. This article presents a secondary analysis
      of a randomized, controlled trial comparing supported employment with 2 other
      vocational rehabilitation programs in 3 ethnic/racial groups of participants with
      severe mental illness: Latinos, non-Latino African Americans, and non-Latino
      Whites. METHOD: The data were drawn from a previously published randomized,
      controlled trial comparing supported employment with standard vocational
      rehabilitation services and a psychosocial clubhouse program in persons with
      severe mental illness (Mueser et al., 2004), including 64 Latinos, 91 non-Latino
      African Americans, and 43 non-Latino Whites. Comparisons were made between the 3
      groups at baseline on demographic characteristics, clinical and psychosocial
      functioning, and quality of life. Within each ethnic/racial group, competitive
      employment and all paid employment outcomes were compared between the 3
      vocational rehabilitation programs over the 2-year study period. RESULTS: At
      baseline, the Latino participants had lower levels of education and disability
      income, were less likely to have worked competitively over the previous 5 years,
      had more severe symptoms, and worse psychosocial functioning than the non-Latino
      African American or non-Latino White participants. Latinos randomized to
      supported employment had better competitive and all-paid work outcomes than those
      assigned to either standard services or the psychosocial clubhouse program,
      similar to the non-Latino consumers. Rates of competitive work for consumers in
      supported employment were comparable across all 3 racial/ethnic groups.
      DISCUSSION: Supported employment is effective at improving competitive work in
      Latinos with severe mental illness. Efforts should be made to increase access to
      supported employment in the growing population of Latinos with severe mental
      illness.

PMID- 24912061
TI  - Individual placement and support in Europe.
AB  - TOPIC: Individual Placement and Support (IPS) is a psychosocial intervention with
      a considerable body of evidence for its effectiveness in helping people with
      severe psychiatric disorders to obtain and maintain competitive jobs. In the last
      decades several European studies have replicated earlier American outcomes,
      generating widespread interest about its implementation in Europe. PURPOSE: This
      article describes and compares details about achievements and challenges of IPS
      in 4 European countries: the United Kingdom, Italy, The Netherlands, and Spain.
      SOURCES USED: This description draws from published and nonpublished material
      about policy, development of services, and services evaluation. RESULTS: In the
      United Kingdom and in The Netherlands, empirical studies exploring the
      consistency of results over time and the effectiveness of IPS adaptations to
      local needs and special population are in course. In the United Kingdom, IPS has
      become national policy, as well as in some regions of Italy and Spain. Training
      is quite extensive in the United Kingdom and in The Netherlands, developing well
      in Italy and Spain. Implementation seems to be less straightforward, mostly
      because of deeply rooted cultural values regarding both work and mental health
      care. Strong local leadership is still required. In all countries contingencies
      related to the current economic crisis seems to have increased interest in IPS.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: With the converging forces of strong
      local leadership, rapid economic changes, and slow cultural shifts, IPS may soon
      become a priority intervention in Europe for ensuring that people living with
      serious mental illnesses are able to obtain competitive employment.

PMID- 24912062
TI  - Effectiveness of individual placement and support for people with severe mental
      illness in The Netherlands: a 30-month randomized controlled trial.
AB  - OBJECTIVE: Whereas in the U.S. and Canada the Individual Placement and Support
      (IPS) model has proven to be highly effective in enhancing employment
      perspectives for persons with severe mental illnesses, the evidence base is less
      abundant in countries with a different socioeconomic climate. The aim of this
      study was to examine the effectiveness of IPS in the Dutch socioeconomic context.
      METHOD: A multisite randomized controlled trial was performed following 151
      persons with severe mental illnesses expressing an explicit wish for regular
      employment, comparing IPS with traditional vocational rehabilitation (TVR).
      Primary outcome was the proportion of persons who were competitively employed
      over a period of 30 months. Secondary outcomes were self-reported quality of
      life, self-esteem and mental health. Additionally, the impact of being engaged in
      competitive employment on these secondary outcomes was examined. RESULTS: In 30
      months, 44% of IPS participants found competitive work, compared with 25% of
      participants supported by TVR. No direct effect of IPS on mental health, self
      esteem or quality of life was found. Being competitively employed before follow
      up measurements was significantly associated with an increase in mental health,
      self-esteem and quality of life. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This
      study strongly confirms that IPS is an effective method in helping people with
      severe mental illnesses find competitive work also in countries characterized by
      a relatively protective socioeconomic climate putting up unintended barriers to
      employment. The implementation of IPS on a larger scale seems warranted, and new
      studies are needed on the mechanisms through which IPS works.

PMID- 24912063
TI  - A randomized controlled trial of individual placement and support in Japan.
AB  - OBJECTIVE: The individual placement and support (IPS) model of supported
      employment has been implemented throughout North America and Europe, with
      multiple randomized controlled trials documenting its effectiveness, but it has
      not been widely implemented in Asia. To date, no rigorous evaluations of IPS have
      been conducted in Japan. We sought to evaluate whether IPS could be implemented
      in Japan and produce superior competitive employment outcomes compared with
      conventional vocational services. METHOD: We employed a randomized controlled
      trial with a 6-month follow-up; 18 participants were randomly assigned to IPS and
      19 to conventional vocational services. We assessed competitive employment rates,
      hours and weeks worked, and wages earned. RESULTS: Over the 6-month follow-up
      period, IPS participants were more likely than those in usual care to work
      competitively (44.4% for IPS vs. 10.5% for controls, p = .022), work more hours
      (mean of 168 hr for IPS vs. 41 hr for controls, p = .002), and work more weeks
      (mean of 6.4 weeks for IPS vs. 1.8 weeks for controls, p = .003). CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: IPS can be implemented in Japan and yield better
      competitive employment outcomes than conventional vocational services. Adoption
      of the IPS model might have a dramatic impact on the mental health service system
      in Japan where psychiatric hospitals play a central role in mental health care.

PMID- 24912064
TI  - Rebirth through supported employment.
AB  - In this column, the author describes how supported employment was a conduit for
      employment for him, and allowed for a remarkable journey of recovery, involving
      discovery and empowerment, incorporation, purpose, and belonging. After two
      decades of unemployment or underemployment, he began to see that work was
      possible through supported education at college, where he excelled. Federal and
      state grants paid for two thirds of his college education. He periodically met
      with a vocational rehabilitation counselor, who was very encouraging. He also had
      a case manager through a private psychiatric organization who provided support.
      The author concludes that the root of his problems was the lack of supports to
      help him become incorporated into society-a lack that ushered in a host of
      problems, probably similar to what others experience. When supports were given,
      many of those symptoms disappeared.

PMID- 24912065
TI  - Editorial comment.

PMID- 24912068
TI  - Knowledge regarding hymens and the sex education of parents.
AB  - The objective of this study was to ascertain beliefs and knowledge of
      pediatricians and parents regarding the hymen and to evaluate parental and
      pediatrician attitudes regarding sex education by pediatricians. Surveys were
      distributed anonymously to parents and pediatricians. Survey questions included
      knowledge of the female hymen and questions regarding attitudes toward sexual
      health education. There was a statistically significant difference in mean
      knowledge scores between pediatricians and parents regarding the hymen (3.7
      versus 1.3; p < 0.0001). Almost two-thirds of pediatricians (63%) felt
      comfortable providing sexual health education directly to their patients, but
      only 41% felt comfortable educating parents. Pediatricians and parents
      demonstrate knowledge gaps about the hymen. 

PMID- 24912067
TI  - Mutant human FUS Is ubiquitously mislocalized and generates persistent stress
      granules in primary cultured transgenic zebrafish cells.
AB  - FUS mutations can occur in familial amyotrophic lateral sclerosis (fALS), a
      neurodegenerative disease with cytoplasmic FUS inclusion bodies in motor neurons.
      To investigate FUS pathology, we generated transgenic zebrafish expressing GFP
      tagged wild-type or fALS (R521C) human FUS. Cell cultures were made from these
      zebrafish and the subcellular localization of human FUS and the generation of
      stress granule (SG) inclusions examined in different cell types, including
      differentiated motor neurons. We demonstrate that mutant FUS is mislocalized from
      the nucleus to the cytosol to a similar extent in motor neurons and all other
      cell types. Both wild-type and R521C FUS localized to SGs in zebrafish cells,
      demonstrating an intrinsic ability of human FUS to accumulate in SGs irrespective
      of the presence of disease-associated mutations or specific cell type. However,
      elevation in relative cytosolic to nuclear FUS by the R521C mutation led to a
      significant increase in SG assembly and persistence within a sub population of
      vulnerable cells, although these cells were not selectively motor neurons. 

PMID- 24912069
TI  - Serious injuries: an additional indicator to fatalities for road safety
      benchmarking.
AB  - OBJECTIVES: Almost all of the current road safety benchmarking studies focus
      entirely on fatalities, which, however, represent only one measure of the
      magnitude of the road safety problem. The main objective of this article was to
      investigate the possibility of including the number of serious injuries in
      addition to the number of fatalities for road safety benchmarking and to further
      illuminate its impact on the countries' rankings. METHODS: We introduced the
      technique of data envelopment analysis (DEA) to the road safety domain and
      developed a DEA-based road safety model (DEA-RS) in this study. Moreover, we
      outlined different types of possible weight restrictions and adopted 2 of them to
      indicate the relationship between road fatalities and serious injuries for the
      sake of rational benchmarking. One was a relative weight restriction based on the
      information of their shadow price, and the other was a virtual weight restriction
      using a priori knowledge about the importance level of these 2 aspects. RESULTS:
      By computing the most optimal road safety risk scores of 10 European countries
      based on the different models, we found that United Kingdom was the only best
      performing country no matter which model was utilized. However, countries such as
      The Netherlands, Sweden, and Switzerland were no longer best-performing when the
      serious injuries were integrated. On the contrary, Spain, which ranked almost at
      the bottom among all of the countries when only the number of road fatalities was
      considered, became a relatively well-performing country when integrating its
      number of serious injuries in the evaluation. In general, no matter whether the
      country's road safety ranking was improved or deteriorated, most of the countries
      achieved a higher risk score when the number of serious injuries was included,
      which implied that compared to the road fatalities, more policy attention has to
      be paid to improve the situation of serious injuries in most countries.
      CONCLUSIONS: Given the importance of considering the serious injuries in addition
      to the fatalities for international benchmarking of road safety, the proposed
      model (i.e., the DEA-RS model with weight restrictions) turned out to be
      effective in deriving reasonable results. We are thereby also inspired to apply
      this kind of model to a more complete road safety benchmarking practice in the
      future when the data on, for example, the number of slight injuries, the degree
      of property damage, and the number of crashes are ready (i.e., comparable) to
      use.

PMID- 24912070
TI  - Greater striatal responses to medication in Parkinson's disease are associated
      with better task-switching but worse reward performance.
AB  - Dopaminergic medication in Parkinson's disease has been proposed to improve
      cognitive processing by modulating the severely depleted dorsal striatum, while
      impairing reward processing by modulating the relatively intact ventral striatum.
      However, there is no direct (neural) evidence for this hypothesis. Here we fill
      this gap by scanning Parkinson's disease patients (n=15) ON and relatively OFF
      their dopaminergic medication using functional magnetic resonance imaging. During
      scanning, patients performed a task that enabled the simultaneous measurement of
      task-switching and reward-related processing. Brain-behavior correlations
      revealed that medication-related increases (ON-OFF) in switch-related BOLD signal
      (switch-repeat) in the dorsomedial striatum were associated, on an individual
      basis, with improvements in task-switching (i.e. a decreased switch cost).
      Conversely, medication-related increases (ON-OFF) in reward-related BOLD signal
      (high-low) in the ventromedial striatum were associated, on an individual basis,
      with impairments in performance in anticipation of reward (i.e. an increased
      reward cost). Linear regression analyses demonstrated that the positive
      relationship between medication-related changes in BOLD and the reward cost was
      unique to the ventromedial striatum, whereas the negative relationship between
      medication-related changes in BOLD and the switch cost was not unique to the
      dorsomedial striatum. These findings extend the dopamine overdose hypothesis,
      according to which dopamine-induced changes in dorsal and ventral striatal
      processing lead to cognitive improvement and impairment respectively.

PMID- 24912071
TI  - A framework for understanding the relationship between externally and internally
      directed cognition.
AB  - Externally directed cognition (EDC) involves attending to stimuli in the external
      environment, whereas internally directed cognition (IDC) involves attending
      internally to thoughts, memories and mental imagery. To date, most studies have
      focused on the competition or trade-offs between these modes of cognition.
      However, both EDC and IDC include a variety of cognitive states that differ along
      multiple dimensions. These dimensions may influence the way in which EDC and IDC
      relate to each other. In this review, we present a novel framework that considers
      whether cognitive resources are oriented externally or internally, and also
      whether a given cognitive state involves intentional (i.e., voluntary) or
      spontaneous (i.e., involuntary) processing. Within this framework, we examine the
      conditions under which EDC and IDC are expected to either compete, or co-occur
      without interference. We argue that EDC and IDC are not inherently antagonistic,
      but when both involve higher levels of intentionality they are increasingly
      likely to compete, due to the capacity limitations of intentional processing. In
      contrast, if one or both involve spontaneous processing, EDC and IDC can co-occur
      with minimal interference given that involuntary processes are not subject to the
      same capacity constraints. A review of the brain regions implicated in EDC and
      IDC suggests that their neural substrates are partially segregated and partially
      convergent. Both EDC and IDC recruit the lateral prefrontal cortex (PFC) during
      intentional processing, and may therefore compete over the processes and
      representational space it supports. However, at lower levels of intentionality,
      EDC and IDC rely on largely distinct neural structures, which may enable their co
      occurrence without interference. The proposal that EDC and IDC can in some cases
      co-occur, provides a framework for understanding the complex mental states that
      underlie theory of mind, creativity, the influence of self-evaluative processing
      on cognitive control, and memory-guided attention. 

PMID- 24912072
TI  - I feel good whether my friends win or my foes lose: brain mechanisms underlying
      feeling similarity.
AB  - People say they enjoy both seeing a preferred social group succeed and seeing an
      adversary social group fail. At the same time, they state they dislike seeing a
      preferred social group fail and seeing an adversary social group succeed. The
      current magnetic resonance imaging study investigated whether-and if so, how-such
      similarities in reported feeling states are reflected in neural activities.
      American football fans anticipated success and failure situations for their
      favorite or their adversary teams. The data support the idea that feeling
      similarities and divergences expressed in verbal reports carry with them
      significant neural similarities and differences, respectively. Desired (favorite
      team likely to win and adversary team likely to lose) rather than undesired
      (favorite team likely to lose and adversary team likely to win) outcomes were
      associated with heightened activity in the supramarginal gyrus, posterior
      cingulate cortex, insula, and cerebellum. Precuneus activity additionally
      distinguished anticipated desirable outcomes for favorite versus adversary teams.

PMID- 24912073
TI  - Drusen and photoreceptor abnormalities in African-Americans with intermediate non
      neovascular age-related macular degeneration.
AB  - PURPOSE/AIM: To investigate the relationship of drusen and photoreceptor
      abnormalities in African-American (AA) patients with intermediate non-neovascular
      age-related macular degeneration (AMD). MATERIALS AND METHODS: AA patients with
      intermediate AMD (n = 11; age 52-77 years) were studied with spectral-domain
      optical coherence tomography. Macular location and characteristics of large
      drusen (>=125 um) were determined. Thickness of photoreceptor laminae was
      quantified overlying drusen and in other macular regions. A patient with advanced
      AMD (age 87) was included to illustrate the disease spectrum. RESULTS: In this AA
      patient cohort, the spectrum of changes known to occur in AMD, including large
      drusen, sub-retinal drusenoid deposits and geographic atrophy, were identified.
      In intermediate AMD eyes (n = 17), there were 183 large drusen, the majority of
      which were pericentral in location. Overlying the drusen there was significant
      thinning of the photoreceptor outer nuclear layer (termed ONL(+)) as well as the
      inner and outer segments (IS + OS). The reductions in IS + OS thickness were
      directly related to ONL(+) thickness. In a fraction (~8%) of paradrusen locations
      with normal lamination sampled within ~280 um of peak drusen height, ONL(+) was
      significantly thickened compared to age and retinal-location-matched normal
      values. Topographical maps of the macula confirmed ONL thickening in regions
      neighboring and distant to large drusen. CONCLUSIONS: We confirm there is a
      pericentral distribution of drusen across AA-AMD maculae rather than the central
      localization in Caucasian AMD. Reductions in the photoreceptor laminae overlying
      drusen are evident. ONL(+) thickening in some macular areas of AA-AMD eyes may be
      an early phenotypic marker for photoreceptor stress.

PMID- 24912074
TI  - Drafting's improvement of 3000-m running performance in elite athletes: is it a
      placebo effect?
AB  - PURPOSE: To determine the effect of drafting on running time, physiological
      response, and rating of perceived exertion (RPE) during 3000-m track running.
      METHODS: Ten elite middle- and long-distance runners performed 3 track-running
      sessions. The 1st session determined maximal oxygen uptake and maximal aerobic
      speed using a lightweight ambulatory respiratory gas-exchange system (K4B2). The
      2nd and the 3rd tests consisted of nondrafting 3000-m running (3000-mND) and 3000
      m running with drafting for the 1st 2000 m (3000-mD) performed on the track in a
      randomized counterbalanced order. RESULTS: Performance during the 3000-mND
      (553.59+/-22.15 s) was significantly slower (P<.05) than during the 3000-mD
      (544.74+/-18.72 s). Cardiorespiratory responses were not significantly different
      between the trials. However, blood lactate concentration was significantly higher
      (P<.05) after the 3000-mND (16.4+/-2.3 mmol/L) than after the 3000-mD (13.2+/-5.6
      mmol/L). Athletes perceived the 3000-mND as more strenuous than the 3000-mD
      (P<.05) (RPE=16.1+/-0.8 vs 13.1+/-1.3). Results demonstrate that drafting has a
      significant effect on performance in highly trained runners. CONCLUSION: This
      effect could not be explained by a reduced energy expenditure or
      cardiorespiratory effort as a result of drafting. This raises the possibility
      that drafting may aid running performance by both physiological and
      nonphysiological (ie, psychological) effects.

PMID- 24912076
TI  - Penile benign mucinous metaplasia.

PMID- 24912075
TI  - Gender issues in antiepileptogenic treatments.
AB  - Disease modification of epilepsy refers to the alleviation of epileptogenesis or
      comorbidities after genetic or acquired epileptogenic brain insults. There are
      currently 30 proof-of-concept experimental pharmacologic studies that have
      demonstrated some beneficial disease-modifying effects. None of these studies,
      however, has yet passed from the laboratory to the clinic. The International
      League Against Epilepsy and American Epilepsy Society working groups on
      antiepileptogenic (AEG) therapies recently released recommendations for
      conducting preclinical AEG studies, taking into account many of the critiques
      raised by previous study designs. One of the issues relates to the lack of
      analysis of AEG efficacy in both sexes. A review of the literature reveals that
      most of the preclinical studies have been performed using male rodents, whereas
      clinical study cohorts include both males and females. Therefore, it is important
      to determine whether sex differences should be taken into account to a greater
      extent than they have been historically at different phases of experimental
      studies. Here we address the following questions based on analysis of available
      experimental AEG studies: (a) whether sex differences should be considered when
      searching for novel AEG targets, (b) how sex differences can affect the
      preclinical AEG study designs and analysis of outcome measures, and (c) what
      factors should be considered when examining the effect of sex on outcome of
      clinical AEG trials or the clinical use of AEGs.

PMID- 24912077
TI  - Synthesis and photophysical characterisation of new fluorescent triazole adenine
      analogues.
AB  - Fluorescent nucleic acid base analogues are powerful probes of DNA structure.
      Here we describe the synthesis and photo-physical characterisation of a series of
      2-(4-amino-5-(1H-1,2,3-triazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl) and 2-(4
      amino-3-(1H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl) analogues via
      Sonogashira cross-coupling and [3 + 2]-cycloaddition reactions as the key steps
      in the synthesis. Compounds with a nitrogen atom in position 8 showed an
      approximately ten-fold increase in quantum yield and decreased Stokes shift
      compared to analogues with a carbon atom in position 8. Furthermore, the
      analogues containing nitrogen in the 8-position showed a more red-shifted and
      structured absorption as opposed to those which have a carbon incorporated in the
      same position. Compared to the previously characterised C8-triazole modified
      adenine, the emissive potential was significantly lower (tenfold or more) for
      this new family of triazoles-adenine compounds. However, three of the compounds
      have photophysical properties which will make them interesting to monitor inside
      DNA. 

PMID- 24912078
TI  - Star block-copolymers: enzyme-inspired catalysts for oxidation of alcohols in
      water.
AB  - A number of fluorous amphiphilic star block-copolymers containing a
      tris(benzyltriazolylmethyl)amine motif have been prepared. These polymers
      assembled into well-defined nanostructures in water, and their mode of assembly
      could be controlled by changing the composition of the polymer. The polymers were
      used for enzyme-inspired catalysis of alcohol oxidation. 

PMID- 24912080
TI  - Immunization Information Systems.

PMID- 24912079
TI  - What does annealing do to metal-graphene contacts?
AB  - Annealing is a postprocessing treatment commonly used to improve metal-graphene
      contacts with the assumption that resist residues sandwiched at the metal
      graphene contacts are removed during annealing. Here, we examine this assumption
      by undertaking a systematic study to understand mechanisms that lead to the
      contact enhancement brought about by annealing. Using a soft shadow-mask, we
      fabricated residue-free metal-graphene contacts with the same dimensions as
      lithographically defined metal-graphene contacts on the same graphene flake. Both
      cases show comparable contact enhancement for nickel-graphene contacts after
      annealing treatment signifying that removal of resist residues is not the main
      factor for contact enhancement. It is found instead that carbon dissolves from
      graphene into the metal at chemisorbed Ni- and Co-graphene interfaces and leads
      to many end-contacts being formed between the metal and the dangling carbon bonds
      in the graphene, which contributes to much smaller contact resistance. 

PMID- 24912081
TI  - Economic review of immunization information systems to increase vaccination
      rates: a community guide systematic review.
AB  - CONTEXT: A recent systematic review found that use of an immunization information
      system (IIS) is an effective intervention to increase vaccination rates. The
      purpose of this review was to evaluate costs and benefits associated with
      implementing, operating, and participating with an IIS. The speed of technology
      change has had an effect on costs and benefits of IIS and is considered in this
      review. EVIDENCE ACQUISITION: An economic evaluation for IIS was conducted using
      methods developed for Community Guide systematic reviews. The literature search
      covered the period from January 1994 to March 2012 and identified 12 published
      articles and 2 government reports. EVIDENCE SYNTHESIS: Most studies involving
      cost data evaluated (1) system costs of building an IIS and (2) cost of
      exchanging immunization data; most economic benefits focused on administrative
      efficiency. CONCLUSIONS: A major challenge to evaluating a technology-based
      intervention is the evolution that comes with technology improvements and
      advancements. Although the cost and benefit data may be less applicable today due
      to changes in system technology, data exchange methods, availability of vendor
      support, system functionalities, and scope of IIS, it is likely that more up-to
      date estimates and comprehensive estimates of benefits would support the findings
      of cost savings in this review. More research is needed to update and address
      limitations in the available evidence and to enable assessment of economic costs
      and benefits of present-day IIS.

PMID- 24912082
TI  - Immunization information systems to increase vaccination rates: a community guide
      systematic review.
AB  - CONTEXT: Immunizations are the most effective way to reduce incidence of vaccine
      preventable diseases. Immunization information systems (IISs) are confidential,
      population-based, computerized databases that record all vaccination doses
      administered by participating providers to people residing within a given
      geopolitical area. They facilitate consolidation of vaccination histories for use
      by health care providers in determining appropriate client vaccinations.
      Immunization information systems also provide aggregate data on immunizations for
      use in monitoring coverage and program operations and to guide public health
      action. EVIDENCE ACQUISITION: Methods for conducting systematic reviews for the
      Guide to Community Preventive Services were used to assess the effectiveness of
      IISs. Reviewed evidence examined changes in vaccination rates in client
      populations or described expanded IIS capabilities related to improving
      vaccinations. The literature search identified 108 published articles and 132
      conference abstracts describing or evaluating the use of IISs in different
      assessment categories. EVIDENCE SYNTHESIS: Studies described or evaluated IIS
      capabilities to (1) create or support effective interventions to increase
      vaccination rates, such as client reminder and recall, provider assessment and
      feedback, and provider reminders; (2) determine client vaccination status to
      inform decisions by clinicians, health care systems, and schools; (3) guide
      public health responses to outbreaks of vaccine-preventable disease; (4) inform
      assessments of vaccination coverage, missed vaccination opportunities, invalid
      dose administration, and disparities; and (5) facilitate vaccine management and
      accountability. CONCLUSIONS: Findings from 240 articles and abstracts demonstrate
      IIS capabilities and actions in increasing vaccination rates with the goal of
      reducing vaccine-preventable disease.

PMID- 24912083
TI  - Recommendation for use of immunization information systems to increase
      vaccination rates.
AB  - Based on findings of a systematic review, the Community Preventive Services Task
      Force recommends immunization information systems on the basis of strong evidence
      of effectiveness in increasing vaccination rates. Evidence is considered strong,
      based on the findings from 108 published articles and 132 conference abstracts
      showing that immunization information systems are effective in increasing
      vaccination rates and reducing vaccine-preventable disease through their
      capabilities to (1) create or support effective interventions such as client
      reminder and recall systems, provider assessment and feedback, and provider
      reminders; (2) generate and evaluate public health responses to outbreaks of
      vaccine-preventable disease; (3) facilitate vaccine management and
      accountability; (4) determine client vaccination status for decisions made by
      clinicians, health departments, and schools; and (5) aid surveillance and
      investigations on vaccination rates, missed vaccination opportunities, invalid
      dose administration, and disparities in vaccination coverage. 

PMID- 24912084
TI  - Effect of Mg2+ cations on the dynamics and efficiency of hole transport in DNA.
AB  - The effect of Mg(2+) cations on the electronic spectra and dynamics and
      efficiency of hole transport has been determined by means of femtosecond time
      resolved transient absorption spectroscopy for DNA hairpins possessing stilbene
      electron acceptor and donor chromophores. The results are compared with those
      obtained previously for the same hairpins in the presence of Na(+) cations and
      for one hairpin with no added salt. Quantum yields and rate constants for charge
      separation are smaller in the presence of Mg(2+) than Na(+), the largest
      differences being observed for the hairpins with the largest number of base
      pairs. Slower charge separation is attributed to minor groove binding by Mg(2+),
      which results in a stiffer duplex structure rather than a change in ground state
      geometry. Reduction in the Na(+) concentration has little effect on either the
      dynamics or efficiency of hole transport. 

PMID- 24912085
TI  - Metagenomic analysis of the viral community in Namib Desert hypoliths.
AB  - Hypolithic microbial communities are specialized desert communities inhabiting
      the underside of translucent rocks. Here, we present the first study of the viral
      fraction of these communities isolated from the hyperarid Namib Desert. The
      taxonomic composition of the hypolithic viral communities was investigated and a
      functional assessment of the sequences determined. Phylotypic analysis showed
      that bacteriophages belonging to the order Caudovirales, in particular the family
      Siphoviridae, were most prevalent. Functional analysis and comparison with other
      metaviromes revealed a relatively high frequency of cell wall-degrading enzymes,
      ribonucleotide reductases (RNRs) and phage-associated genes. Phylogenetic
      analyses of terL and phoH marker genes indicated that many of the sequences were
      novel and distinct from known isolates, and the class distribution of the RNRs
      suggests that this is a novel environment. The composition of the viral hypolith
      fraction containing many Bacillus-infecting phages was not completely consistent
      with Namib hypolith phylotypic surveys of the bacterial hosts, in which the
      cyanobacterial genus Chroococcidiopsis was found to be dominant. This could be
      attributed to the lack of sequence information about hypolith viruses/bacteria in
      public databases or the possibility that hypolithic communities incorporate
      viruses from the surrounding soil. 

PMID- 24912086
TI  - Reduced fetal movements at 27 weeks: an alarm for maternal-fetal listeriosis?

PMID- 24912087
TI  - A co-assembled gel of a pyromellitic dianhydride derivative and polyaniline with
      optoelectronic and photovoltaic properties.
AB  - 5,5'-(1,3,5,7-Tetraoxopyrrolo[3,4-f]isoindole-2,6-diyl)diisophthalic acid (PMDIG)
      is used to produce a supramolecular hydrogel via acid-base treatment. The field
      emission scanning electron micrograph and atomic force microscopy micrographs
      exhibit a fibrillar network structure from intermolecular supramolecular
      interaction, supported from Fourier transform infrared (FTIR) and UV-vis spectra.
      The fluorescence intensity of the PMDIG gel is 16 times higher than that of the
      sodium salt of PMDIG with a 42 nm red shift of the emission peak. Upon addition
      of an anilinium chloride solution to the PMDIG gel, it transforms into the sol,
      and when a solid ammonium persulfate is spread over it, a stable hydrogel is
      produced. The co-assembled PMDIG-polyaniline (PANI) gel exhibits a fibrillar
      network morphology, and the co-assembly is formed by the supramolecular
      interaction between the polyaniline (donor) and the PMDIG (acceptor) molecules,
      which is evident from FTIR spectra and wide angle X-ray scattering results. The
      UV-vis spectrum of the PMDIG-PANI hydrogel exhibits the characteristic peaks of
      polaron band transitions of the doped PANI. The PMDIG-PANI co-assembled hydrogel
      has a 51-fold higher storage modulus, a 52-fold higher elasticity, a 1.4-fold
      increase in stiffness, and a 5-fold increase of fragility compared to the values
      of the PMDIG hydrogel. The PMDIG-PANI xerogel exhibits a 4 order of magnitude
      increase in dc conductivity compared to that of PMDIG, and the I-V characteristic
      curve exhibits a rectification property under white light illumination showing
      photocurrent rectification, a new phenomenon reported here for the supramolecular
      gel systems. A dye-sensitized solar cell fabricated with an ITO/PMDIG
      PANI/graphite device shows a power conversion efficiency (eta) of 0.1%. A
      discussion of the mechanism of gel formation and the sol state of the PMDIG
      aniline system is included considering the contact angle values of the xerogels. 

PMID- 24912088
TI  - Effectiveness of Alpha-toxin Fab Monoclonal Antibody Therapy in Limiting the
      Pathology of Staphylococcus aureus Keratitis.
AB  - PURPOSE: To investigate the effectiveness of a high-affinity human monoclonal
      antibody Fab fragment to Staphylococcus aureus alpha-toxin (LTM14 Fab) as therapy
      for S. aureus keratitis. METHODS: A single topical drop of the LTM14 Fab antibody
      to alpha-toxin alone, or in 0.006% benzalkonium chloride (BAK), was applied every
      30 min to S. aureus-infected rabbit corneas from 9 to 14 hours post-infection.
      Erosions and pathology were measured at 15 h post-infection. RESULTS: LTM14 Fab
      with BAK limited corneal erosions better than LTM14 Fab alone (p = 0.036), and
      both limited erosions compared to untreated eyes (p <= 0.0001). Overall pathology
      was similar in all groups (p >= 0.070), but iritis and chemosis were reduced by
      treatment (p <= 0.036). CONCLUSIONS: The high-affinity human monoclonal Fab
      fragment antibody (LTM14 Fab) to S. aureus alpha-toxin was effective in reducing
      corneal damage during S. aureus keratitis.

PMID- 24912089
TI  - Intravital multiphoton fluorescence imaging and optical manipulation of spinal
      cord in mice, using a compact fiber laser system.
AB  - BACKGROUND AND OBJECTIVE: Near-infrared ultrafast lasers are widely used for
      multiphoton excited fluorescence microscopy in living animals. Ti:Sapphire lasers
      are typically used for multiphoton excitation, but their emission wavelength is
      restricted below 1,000 nm. The aim of this study is to evaluate the performance
      of a compact Ytterbium-(Yb-) fiber laser at 1,045 nm for multiphoton excited
      fluorescence microscopy in spinal cord injury. MATERIALS AND METHODS: In this
      study, we employed a custom-designed microscopy system with a compact Yb-fiber
      laser and evaluated the performance of this system in in vivo imaging of brain
      cortex and spinal cord in YFP-H transgenic mice. RESULTS: For in vivo imaging of
      brain cortex, sharp images of basal dendrites, and pyramidal cells expressing
      EYFP were successfully captured using the Yb-fiber laser in our microscopy
      system. We also performed in vivo imaging of axon fibers of spinal cord in the
      transgenic mice. The obtained images were almost as sharp as those obtained using
      a conventional ultrafast laser system. In addition, laser ablation and multi
      color imaging could be performed simultaneously using the Yb-fiber laser.
      CONCLUSION: The high-peak pulse Yb-fiber laser is potentially useful for
      multimodal bioimaging methods based on a multiphoton excited fluorescence
      microscopy system that incorporates laser ablation techniques. Our results
      suggest that microscopy systems of this type could be utilized in studies of
      neuroscience and clinical use in diagnostics and therapeutic tool for spinal cord
      injury in the future.

PMID- 24912090
TI  - Human risk assessment of dermal and inhalation exposures to chemicals assessed by
      route-to-route extrapolation: the necessity of kinetic data.
AB  - In toxicity testing the oral route is in general the first choice. Often,
      appropriate inhalation and dermal toxicity data are absent. Risk assessment for
      these latter routes usually has to rely on route-to-route extrapolation starting
      from oral toxicity data. Although it is generally recognized that the
      uncertainties involved are (too) large, route-to-route extrapolation is applied
      in many cases because of a strong need of an assessment of risks linked to a
      given exposure scenario. For an adequate route-to-route extrapolation the
      availability of at least some basic toxicokinetic data is a pre-requisite. These
      toxicokinetic data include all phases of kinetics, from absorption (both absorbed
      fraction and absorption rate for both the starting route and route of interest)
      via distribution and biotransformation to excretion. However, in practice only
      differences in absorption between the different routes are accounted for. The
      present paper demonstrates the necessity of route-specific absorption data by
      showing the impact of its absence on the uncertainty of the human health risk
      assessment using route-to-route extrapolation. Quantification of the absorption
      (by in vivo, in vitro or in silico methods), particularly for the starting route,
      is considered essential. 

PMID- 24912091
TI  - Bacterial spectrum and antimicrobial susceptibility patterns in acquired and
      connatal lacrimal duct stenosis.
AB  - PURPOSE: (1) To determine the current bacteriological spectrum in connatal and
      acquired lacrimal duct obstruction (cLDO and aLDO, respectively) and (2) to
      analyze the antimicrobial susceptibility patterns of the recovered isolates.
      MATERIALS AND METHODS: In a prospective study, 463 samples (30% bilateral LDO)
      were obtained from the lacrimal ducts of 132 infants and 192 adult patients with
      symptomatic LDO between 2007 and 2012 at a tertiary eye-care center. The samples
      were cultured for aerobic and anaerobic bacteria, which were subsequently
      identified using standard microbiological techniques. Antimicrobial
      susceptibility testing was performed for each isolate using the disk diffusion
      method. Data were analyzed using SPSS and chi-square test for significance
      testing. RESULTS: (1) Among 463 samples investigated, 333 samples were positive,
      i.e. at least one bacterial isolate was recovered. A total of 72% were recovered
      (97% of samples from children and 56% of samples from adults), yielding a total
      of 654 bacterial isolates. Co-colonization with up to five different bacterial
      species was observed in a large proportion of the samples from children (87%),
      but in only 20% of those from adults and with a maximum of three different
      bacteria. Gram-positive bacteria were identified in 72% of the positive samples
      in both aLDO and cLDO. The most common Gram-positive species in cLDO was
      Streptococcus pneumoniae (29%), while that in cLDO was Staphylococcus aureus
      (60%). The most prevalent Gram-negative species were Moraxella catarrhalis (8%)
      and Haemophilus influenzae (9%) in cLDO and Pseudomonas aeruginosa in aLDO (12%).
      (2) Susceptibility testing revealed chloramphenicol to be the most active
      antibiotic with resistance rates of 3% in cLDO and 6% in aLDO, followed by
      ciprofloxacin (1% and 6%). Erythromycin and gentamicin were the least active of
      all, with resistances of 41% and 22%, respectively, in cLDO, and 23% and 11% in
      aLDO. CONCLUSIONS: Bacterial colonization occurs regularly in LDO, with Gram
      positive bacteria being found in 97% of cLDO samples and 56% of aLDO samples. A
      remarkable number of different species were found to co-colonize in cLDO. The
      most common bacteria in LDO are highly susceptible in vitro to chloramphenicol
      and ciprofloxacin.

PMID- 24912093
TI  - Trends in pregnancy labeling and data quality for US-approved pharmaceuticals.
AB  - OBJECTIVE: Over the past decades, there have been significant efforts in the
      United States to improve pharmaceutical labeling pertaining to pregnancy. The
      goal of this study was to describe trends in pregnancy labeling at the time of
      drug approval and over time. STUDY DESIGN: The labeling data of 213 new
      pharmaceutical approvals between January 2003 and December 2012 were
      systematically reviewed. Initial approval data and subsequent labeling revisions
      were evaluated for pregnancy category, source of pregnancy and breast-feeding
      data, data in labor and delivery, presence of a registry, black-box warnings, and
      utilization of the new labeling format. RESULTS: The most commonly approved
      pregnancy category was C (51.6%). Most pharmaceuticals (92.9%) had pregnancy data
      based on animal studies and 5.2% had human pregnancy data. For breast-feeding,
      there were no data in 47.9% of labels, animal data in 42.7%, and human data in
      4.7%. There were no labor and delivery data in 85.9% of labels. Only 2.8% of
      medications had human data, with the remainder having animal data. The majority
      of medications (85%) did not have a pregnancy registry. Of those that had a
      registry, 68.7% were by therapeutic category, not agent specific. Seven
      medications had black-box warnings related to teratogenicity. Since the new
      labeling recommendations, 4.7% of medications incorporated the new format into
      the labeling, primarily approvals that occurred in 2012. CONCLUSION: Despite
      significant efforts to improve drug labeling for pregnancy and lactation, there
      remains a paucity of human data in this understudied population.

PMID- 24912092
TI  - Histone deacetylase inhibition destabilizes the multi-potent state of uncommitted
      adipose-derived mesenchymal stromal cells.
AB  - Human adipose-derived mesenchymal stromal cells (AMSCs) grown in platelet lysate
      are promising agents for therapeutic tissue regeneration. Here, we investigated
      whether manipulation of epigenetic events by the clinically relevant histone
      deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alters
      differentiation of AMSCs. The multipotency of AMSCs was validated by their
      ability to differentiate into osteogenic, chondrogenic, and adipogenic lineages.
      High-throughput RNA sequencing and RT-qPCR established that human histone
      deacetylases (HDAC1 to HDAC11, and SIRT1 to SIRT7) are differentially expressed
      in AMSCs. SAHA induces hyper-acetylation of histone H3 and H4, stimulates protein
      expression of the HDAC-responsive gene SLC9A3R1/NHERF1 and modulates the
      AKT/FOXO1 pathway. Biologically, SAHA interferes with osteogenic, chondrogenic
      and adipogenic lineage commitment of multipotent AMSCs. Mechanistically, SAHA
      induced loss of differentiation potential of uncommitted AMSCs correlates with
      multiple changes in the expression of principal transcription factors that
      control mesenchymal or pluripotent states. We propose that SAHA destabilizes the
      multi-potent epigenetic state of uncommitted human AMSCs by hyper-acetylation and
      perturbation of key transcription factor pathways. Furthermore, AMSCs grown in
      platelet lysate may provide a useful biological model for screening of new HDAC
      inhibitors that control the biological fate of human mesenchymal stromal cells.

PMID- 24912094
TI  - An unexpected mass of the urachus: a case report.
AB  - The urachus is a remnant of the urogenital sinus and allantois, which persists
      after antenatal involution. Despite its rudimentary postnatal presence, it can
      undergo metaplasia and tumor formation. Malignant transformation of the urachus
      is rare. However, these tumors can recur and develop pseudomyxoma peritonei.
      Thus, they should remain on the differential for any female patient with a pelvic
      mass. A 28-year old G9P2062 presented at 8 weeks' gestation requesting pregnancy
      termination. On ultrasound, a single live intrauterine pregnancy was visualized.
      Also identified was a left-sided 8- * 7- * 6-cm complex echogenic mass with
      thickened septations, heterogeneous appearance, and fluid-fluid levels suspicious
      for a mature cystic teratoma. Surgical termination of pregnancy and diagnostic
      laparoscopy was planned. Intraoperatively a multiloculated midline mass was
      identified and excised. Final pathology identified a mucinous urachal neoplasm of
      low malignant potential. The patient followed up with urology and underwent
      surgical staging. Midline location is a key feature that helps distinguish
      ovarian masses from urachal or bladder masses. Many urachal and bladder neoplasms
      are managed with complete surgical excision and staging, illustrating the
      importance of preoperative identification. If laterality of a mass is unclear,
      further imaging is recommended to characterize the mass preoperatively. This case
      also reveals the feasibility of a minimally invasive abdominal wall mass
      resection. 

PMID- 24912095
TI  - Use of hemoglobin A1c as an early predictor of gestational diabetes mellitus.
AB  - OBJECTIVE: The purpose of this study was to assess an early hemoglobin A1c
      (HgbA1c) value from 5.7-6.4% as an early predictor of progression to gestational
      diabetes (GDM). STUDY DESIGN: A retrospective cohort study was performed on all
      women who delivered at a single institution over 2 years who had an early
      screening HgbA1c test performed at <=20 weeks of gestation. Women with known
      preexisting diabetes mellitus or HgbA1c values >=6.5% were excluded. The primary
      outcome was GDM development. Secondary outcomes included delivery route, maternal
      weight gain, birthweight, and neonatal morbidities. Women with an HgbA1c value of
      5.7-6.4% were compared with those with an HgbA1c level of <5.7%. RESULTS: Nearly
      one-third of those patients in the HgbA1c 5.7-6.4% group (27.3%) experience the
      development of GDM compared with only 8.7% in the HgbA1c <5.7% group (odds ratio,
      3.9; 95% confidence level, 2.0-7.7). This 3-fold increase remained significant
      (adjusted odds ratio, 2.4) after adjustment for age, prepregnancy body mass
      index, gestational age at HgbA1c collection, gestational age at screening,
      ethnicity, and method of screening. There were no significant differences in the
      need for medical treatment, weight gain, delivery route, birthweight, macrosomia,
      or neonatal morbidities. CONCLUSION: More than 10% of patients in our cohort had
      an early screening HgbA1c value of 5.7-6.4%. Women in this group have a
      significantly higher risk of progression to GDM compared with women with normal
      HgbA1c values and should be considered for closer GDM surveillance and possible
      intervention.

PMID- 24912096
TI  - Impact of single- vs double-layer closure on adverse outcomes and uterine scar
      defect: a systematic review and metaanalysis.
AB  - A systematic review and metaanalysis were performed through electronic database
      searches to estimate the effect of uterine closure at cesarean on the risk of
      adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized
      controlled trials, which compared single vs double layers and locking vs
      unlocking sutures for uterine closure of low transverse cesarean, were included.
      Outcomes were short-term complications (endometritis, wound infection, maternal
      infectious morbidity, blood transfusion, duration of surgical procedure, length
      of hospital stay, mean blood loss), uterine rupture or dehiscence at next
      pregnancy, and uterine scar evaluation by ultrasound. Twenty of 1278 citations
      were included in the analysis. We found that all types of closure were comparable
      for short-term maternal outcomes, except for single-layer closure, which had
      shorter operative time (-6.1 minutes; 95% confidence interval [CI], -8.7 to -3.4;
      P < .001) than double-layer closure. Single layer (-2.6 mm; 95% CI, -3.1 to -2.1;
      P < .001) and locked first layer (mean difference, -2.5 mm; 95% CI, -3.2 to -1.8;
      P < .001) were associated with lower residual myometrial thickness. Two studies
      reported no significant difference between single- vs double-layer closure for
      uterine dehiscence (relative risk, 1.86; 95% CI, 0.44-7.90; P = .40) or uterine
      rupture (no case). In conclusion, current evidence based on randomized trials
      does not support a specific type of uterine closure for optimal maternal outcomes
      and is insufficient to conclude about the risk of uterine rupture. Single-layer
      closure and locked first layer are possibly coupled with thinner residual
      myometrium thickness.

PMID- 24912098
TI  - Quality of first-trimester measurement of crown-rump length.
AB  - OBJECTIVE: The purpose of this study was to evaluate the quality of crown-rump
      length (CRL) measurements in scans judged to be of high quality for the
      measurement of the nuchal translucency. STUDY DESIGN: We analyzed prospective
      data on 68,250 scans by 1913 sonographers that were collected by the French
      College of Fetal Echography (CFEF) national practice assessment program for the
      first-trimester scan. The scans were evaluated according to the CFEF image
      scoring method (CFEF-ISM), which includes items to measure the quality of the
      scan for both nuchal translucency and the CRL measurements. The scans were
      classified into 4 quality groups with the use of the full CFEF-ISM score and then
      a shortened version of the CFEF-ISM that excluded the item on quality of CRL
      measurement. The proportion of scans with an inaccurate CRL measurement was
      compared across the different quality groups. RESULTS: Overall, 21.67% of scans
      were of insufficient quality for CRL measurement. Among 23,764 "excellent" scans
      according to the full CFEF-ISM, 965 scans (4.06%) had insufficient CRL quality vs
      9.24% of scans with "excellent" quality on the short CFEF-ISM (relative risk,
      2.27; 95% confidence interval, 2.11-2.44; P < .001). CONCLUSION: High scores of
      the quality of nuchal translucency measurement do not guarantee accurate
      measurement of crown-rump length. Specific measures are needed to evaluate and to
      improve the quality of the measurement of crown-lump length.

PMID- 24912100
TI  - Versatile supramolecular organogel with outstanding stability toward aqueous
      interfaces.
AB  - In this communication, we report on a novel and versatile low-molecular-weight
      organogelator. The methanolic gel exhibits an exceptional water-enhanced
      stability as evidenced by a 30  degrees C increase in Tg with up to 10%v/v of
      water. This atypical property not observed with other solvents makes of this
      supramolecular gel a highly stable matrix compatible with aqueous interfaces. As
      a proof of principle we present the sensing performance of a symmetric
      tricarbocyanine fluorophore bearing a Zn(II)chelator unit. The system retained
      its remarkable physical integrity for a long period of time opening new
      possibilities for other organic-aqueous interface applications. 

PMID- 24912097
TI  - What is the optimal gestational age for women with gestational diabetes type A1
      to deliver?
AB  - OBJECTIVE: Type A1 gestational diabetes mellitus (A1GDM), also known as diet
      controlled gestational diabetes, is associated with an increase in adverse
      perinatal outcomes such as macrosomia and Erb palsy. However, it remains unclear
      when to deliver these women because optimal timing of delivery requires balancing
      neonatal morbidities from early term delivery against the risk of intrauterine
      fetal demise (IUFD). We sought to determine the optimal gestational age (GA) for
      women with A1GDM to deliver. STUDY DESIGN: A decision-analytic model was built to
      compare the outcomes of delivery at 37-41 weeks in a theoretical cohort of
      100,000 women with A1GDM. Strategies involving expectant management until a later
      GA accounted for probabilities of spontaneous delivery, indicated delivery, and
      IUFD during each week. GA-associated risks of neonatal complications included
      cerebral palsy, infant death, and Erb palsy. Probabilities were derived from the
      literature, and total quality-adjusted life years were calculated. Sensitivity
      analyses were used to investigate the robustness of the baseline assumptions.
      RESULTS: Our model showed that induction at 38 weeks maximized quality-adjusted
      life years. Within our cohort, delivery at 38 weeks would prevent 48 stillbirths
      but lead to 12 more infant deaths compared to 39 weeks. Sensitivity analysis
      revealed that 38 weeks remains the optimal timing of delivery until IUFD rates
      fall <0.3-fold of our baseline assumption, at which point expectant management
      until 39 weeks is optimal. CONCLUSION: By weighing the risks of IUFD against
      infant deaths and neonatal morbidities from early term delivery, we determined
      that the ideal GA for women with A1GDM to deliver is 38 weeks.

PMID- 24912101
TI  - Evaluation of Assessment of Spondyloarthritis International Society
      classification criteria for axial spondyloarthritis in Chinese patients with
      chronic back pain: results of a 2-year follow-up study.
AB  - OBJECTIVE: To evaluate the diagnotic value of the Assessment of Spondyloarthritis
      International Society (ASAS) classification criteria for axial spondyloarthritis
      (SpA) in Chinese patients with chronic back pain and without radiographic
      sacroiliitis in a 2-year follow-up study. METHODS: Patients with chronic back
      pain >= 3 months, onset age <= 45 years and without radiographic sacroiliitis
      were enrolled, and then received 2-year follow-up. All the clinical parameters
      associated with SpA were recorded. The patients were followed for 2 years and the
      final diagnosis of axial SpA or non-SpA was confirmed by rheumatologists.
      Diagnostic concordance between the initial classification according to three
      classification criteria (ASAS criteria for axial SpA, European Spondylarthropathy
      Study Group (ESSG) criteria and Amor criteria) and final diagnosis was compared.
      Diagnostic sensitivity and specificity were compared between the two subsets of
      ASAS criteria (set 1: sacroiliitis plus more than one SpA feature; set 2: HLA-B27
      plus two more SpA features). RESULT: One thousand and sixty-eight patients
      entered the study and 867 completed the 2-year follow-up (455 axial SpA and 412
      non-SpA). The concordance of ASAS criteria was better than ESSG and Amor
      criteria. Three hundred and thirty-three patients and 335 patients were
      classified as axial SpA according to the ASAS set 1 and set 2 of criteria,
      respectively. Further, set 1 of criteria (318/333) showed higher specificity than
      set 2 critera (279/335) (P = 0.000). CONCLUSION: The ASAS classification criteria
      for axial SpA showed good concordance in diagnosing Chinese axial SpA patients in
      this prospective study. Set 1 criteria involving sacroiliitis plus more than one
      SpA feature had better diagnosing value.

PMID- 24912102
TI  - Memory impairment among people who are homeless: a systematic review.
AB  - Cognitive impairment may interfere with an individual's ability to function
      independently in the community and may increase the risk of becoming and
      remaining homeless. The purpose of this study was to systematically review the
      literature on memory deficits among people who are homeless in order to gain a
      better understanding of its nature, causes and prevalence. Studies that measured
      memory functioning as an outcome among a sample of homeless persons were
      included. Data on sampling, outcome measures, facet of memory explored and
      prevalence of memory impairment were extracted from all selected research
      studies. Included studies were evaluated using a critical appraisal process
      targetted for reviewing prevalence studies. Eleven studies were included in the
      review. Verbal memory was the most commonly studied facet of memory. Potential
      contributing factors to memory deficits among persons who are homeless were
      explored in seven studies. Memory deficits were common among the samples of
      homeless persons studied. However, there was a great deal of variation in the
      methodology and quality of the included studies. Conceptualisations of
      "homelessness" also differed across studies. There is a need for more controlled
      research using validated neuropsychological tools to evaluate memory impairment
      among people who are homeless.

PMID- 24912103
TI  - Alkaline hydrolysis of organophosphorus pesticides: the dependence of the
      reaction mechanism on the incoming group conformation.
AB  - The fundamental mechanism of organophosphate hydrolysis is the subject of a
      growing interest resulting from the need for safe disposal of phosphoroorganic
      pesticides. Herein, we present a detailed ab initio study of the gas-phase
      mechanisms of alkaline hydrolysis of P-O and P-S bonds in a number of
      organophosphorus pesticides, including paraoxon, methyl parathion, fenitrothion,
      demeton-S, acephate, phosalone, azinophos-ethyl, and malathion. Our main finding
      is that the incoming group conformation influences the mechanism of decomposition
      of organophosphate and organothiophosphate compounds. Depending on the
      orientation of the attacking nucleophile, hydrolysis reaction might follow either
      a multistep pathway characterized by the presence of a pentavalent intermediate
      or a one-step mechanism proceeding through a single transition state. Despite a
      widely accepted view of the phosphotriester P-O bonds being decomposed
      exclusively via a direct-displacement mechanism, the occurrence of alternative,
      qualitatively distinct reaction pathways was confirmed for alkaline hydrolysis of
      both P-O and P-S bonds. As the pesticides included in our quantum chemical
      analysis involve organophosphate, phosphorothioate, and phosphorodithioate
      compounds, the influence of oxygen to sulfur substitution on the structural and
      energetic characteristics of the hydrolysis pathway is also discussed. 

PMID- 24912104
TI  - A shortcut to wide-ranging biological actions of dietary polyphenols: modulation
      of the nitrate-nitrite-nitric oxide pathway in the gut.
AB  - Dietary polyphenols are complex, natural compounds with recognized health
      benefits. Initially attractive to the biomedical area due to their in vitro
      antioxidant properties, the biological implications of polyphenols are now known
      to be far from their acute ability to scavenge free radicals but rather to
      modulate redox signaling pathways. Actually, it is now recognized that dietary
      polyphenols are extensively metabolized in vivo and that the chemical,
      biophysical and biological properties of their metabolites are, in most cases,
      quite different from the ones of the parent molecules. Hence, the study of the
      metabolic, absorptive and signaling pathways of both phenolics and derivatives
      has become a major issue. In this paper we propose a short-cut for the systemic
      effects of polyphenols in connection with nitric oxide (NO) biology. This free
      radical is a ubiquitous signaling molecule with pivotal functions in vivo. It is
      produced through an enzymatic pathway and also through the reduction of dietary
      nitrate and nitrite in the human stomach. At acidic gastric pH, dietary
      polyphenols, in the form they are conveyed in foods and at high concentration,
      not only promote nitrite reduction to NO but also embark in a complex network of
      chemical reactions to produce higher nitrogen oxides with signaling functions,
      namely by inducing post-translational modifications. Modified endogenous
      molecules, such as nitrated proteins and lipids, acquire important physiological
      functions. Thus, local and systemic effects of NO such as modulation of vascular
      tone, mucus production in the gut and protection against ischemia-reperfusion
      injury are, in this sense, triggered by dietary polyphenols. Evidence to support
      the signaling and biological effects of polyphenols by modulation of the nitrate
      nitrite-NO pathway will be herein provided and discussed. General actions of
      polyphenols encompassing absorption and metabolism in the intestine/liver are
      short-cut via the production of diffusible species in the stomach that have not
      only a local but also a general impact. 

PMID- 24912105
TI  - Cyclopent-4-ene-1,3-diones: a new class of herbicides acting as potent
      photosynthesis inhibitors.
AB  - In a recent paper, we reported the synthesis and photosynthesis-inhibitory
      activity of a series of analogues of rubrolides. From quantitative structure
      activity relationship (QSAR) studies, we found that the most efficient compounds
      are those having higher ability to accept electrons. On the basis of those
      findings, we directed our effort to synthesize new analogues bearing a strong
      electron-withdrawing group (nitro) in the benzylidene ring and evaluate their
      effects on photosynthesis. However, the employed synthetic approach led to novel
      cyclopent-4-ene-1,3-diones as major products. Here, we report the synthesis and
      mechanism of action of such cyclopent-4-ene-1,3-diones as a new class of
      photosynthesis inhibitors. These compounds block the electron transport at the QB
      level by interacting at the D1 protein at the reducing side of Photosystem II and
      act as Hill reaction inhibitors, with higher activity than the corresponding
      rubrolides. To the best of our knowledge, this is the first report on the
      photosynthesis inhibitory activity of cyclopentenediones. 

PMID- 24912107
TI  - Phytoremediation of soils co-contaminated by organic compounds and heavy metals:
      bioassays with Lupinus luteus L. and associated endophytic bacteria.
AB  - In the central part of the Iberian Peninsula there are old sealed landfills
      containing soils co-contaminated by several heavy metals (Cu, Zn, Pb, Cd, Ni, As,
      Cr, Fe, Al, Mn) and organic pollutants of different families (hydrocarbons,
      polycyclic aromatic hydrocarbons, polychlorinated biphenyls, pesticides and other
      organochlorinated compounds, phenols and volatile compounds), which this work
      will address. We have focused on phytoremedial plants that are able to deal with
      this type of complex pollution, not only species that tolerate the joint effect
      of heavy metals in the soil, but also those that can take advantage of associated
      bacteria to efficiently break down organic compounds. This study was carried out
      with Lupinus luteus and its endophytes in two greenhouse experiments: A) growing
      in a substrate artificially contaminated with benzo(a)pyrene (BaP), and B) using
      real co-contaminated landfill soils. Endophytes of roots and shoots were isolated
      in both bioassays. Plant growth-promotion tests and organic pollutant tolerance
      and degradation tests were conducted on all strains isolated in bioassay A), and
      on those proving to be pure cultures from bioassay B). The selected landfill is
      described as are isolation and test procedures. Results indicate that plants did
      not show toxicity symptoms when exposed to BaP but did when grown in landfill
      soil. Some endophytes demonstrated plant growth-promotion capacity and tolerance
      to BaP and other organic compounds (diesel and PCB commercial mixtures). A few
      strains may even have the capacity to metabolize those organic pollutants. The
      overall decline in plant growth-promotion capacity in those strains isolated from
      the landfill soil experiment, compared with those from the bioassay with BaP, may
      indicate that lupin endophytes are not adapted to metal concentration in roots
      and shoots and fail to grow. As a result, most isolated root endophytes must have
      colonized root tissues from the soil. While preliminary degradation tests showed
      promising results (some strains exhibiting the potential to use organic
      pollutants as their sole source of carbon), these are not conclusive and further
      in-depth degradation assays need to be performed. 

PMID- 24912106
TI  - Prognostic subgroups for citalopram response in the STAR*D trial.
AB  - OBJECTIVE: Few data exist to help clinicians predict likelihood of treatment
      response in individual patients with major depressive disorder (MDD). Our aim was
      to identify subgroups of MDD patients with differential treatment outcomes based
      on presenting clinical characteristics. We also sought to quantify the likelihood
      of treatment success based on the degree of improvement and side effects after 2
      and 4 weeks of selective serotonin reuptake inhibitor (SSRI) pharmacotherapy.
      METHOD: We analyzed data from the first treatment phase of the Sequenced
      Treatment Alternatives to Relieve Depression (STAR*D) trial, in which subjects
      with a DSM-IV diagnosis of MDD were treated for 8-14 weeks with open-label
      citalopram. A receiver operating characteristic (ROC) analysis was conducted to
      determine homogenous subgroups with different rates of response and remission in
      depressive symptoms. Included predictor variables were initial clinical
      characteristics, initial improvement, and side effects after 2 and 4 weeks of
      SSRI treatment. The primary outcome measures were treatment response (defined as
      a greater than 50% reduction in 17-item Hamilton Depression Rating Scale [HDRS
      17] score from baseline) and remission (defined as an HDRS-17 score <= 17).
      RESULTS: Baseline clinical characteristics were able to identify subgroups from a
      low likelihood of response of 18% (income < $10,000, comorbid generalized anxiety
      disorder, < 16 years of education; P < .01) to a high likelihood of response of
      68% (income >= $40,000, no comorbid posttraumatic stress disorder; P < .01).
      Among baseline clinical characteristics, employment status (N = 2,477; chi21 =
      78.1; P < .001) and income level (N = 2,512; chi21 = 77.7; P < .001) were the
      most informative in predicting treatment outcome. For the models at weeks 2 and
      4, treatment success was best predicted by early symptom improvement.
      CONCLUSIONS: Socioeconomic data such as low income, education, and unemployment
      were most discriminative in predicting a poor response to citalopram, even with
      disparities in access to care accounted for. This finding implies that
      socioeconomic factors may be more useful predictors of medication response than
      traditional psychiatric diagnoses or past treatment history. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00021528.

PMID- 24912108
TI  - Selection of unique Escherichia coli clones by random amplified polymorphic DNA
      (RAPD): Evaluation by whole genome sequencing.
AB  - Identifying and characterizing clonal diversity are important when analysing
      fecal flora. We evaluated random amplified polymorphic DNA (RAPD) PCR, applied
      for selection of Escherichia coli isolates, by whole genome sequencing. RAPD was
      fast, and reproducible as screening method for selection of distinct E. coli
      clones in fecal swabs. 

PMID- 24912109
TI  - Diastereomeric aziridine carbinol catalyzed enantioselective arylation reaction:
      toward the asymmetric synthesis of both enantiomers of chiral 3-aryl phthalide.
AB  - The diastereomeric aziridine carbinols are applied, respectively, as efficient
      chiral ligand in the catalysis of asymmetric arylation and sequential arylation
      lactonization cascade. The two diastereomers, which are facilely synthesized from
      the same chiral source, function as pseudo enantiomers in arylation of aromatic
      aldehydes providing the different enantiomers of the diarylmethanols with almost
      the same excellent enantioselectivities. The arylation method is also carried out
      in tandem with lactonization process to afford a concise synthetic approach to
      both enantiomers of optically active 3-aryl phthalide. 

PMID- 24912111
TI  - alpha-Gel formation by amino acid-based gemini surfactants.
AB  - Ternary mixtures being composed of surfactant, long-chain alcohol, and water
      sometimes form a highly viscous lamellar gel with a hexagonal packing arrangement
      of their crystalline hydrocarbon chains. This molecular assembly is called "alpha
      crystalline phase" or "alpha-gel". In this study, we have characterized alpha
      gels formed by the ternary mixtures of amino acid-based gemini surfactants, 1
      hexadecanol (C16OH), and water. The surfactants used in this study were
      synthesized by reacting dodecanoylglutamic acid anhydride with alkyl diamines and
      abbreviated as 12-GsG-12 (s: the spacer chain length of 2, 5, and 8 methylene
      units). An amino acid-based monomeric surfactant, dodecanoylglutamic acid (12
      Glu), was also used for comparison. At a fixed water concentration the melting
      point of the alpha-gel increased with increasing C16OH concentration, and then
      attained a saturation level at the critical mole ratio of 12-GsG-12/C16OH = 1/2
      under the normalization by the number of hydrocarbon chains of the surfactants.
      This indicates that, to obtain the saturated alpha-gel, a lesser amount of C16OH
      is required for the gemini surfactants than for the monomeric one (the critical
      mole ratio of 12-Glu/C16OH = 1/3). Small- and wide-angle X-ray scattering
      measurements demonstrated an increase in the long-range d-spacing of the
      saturated alpha-gels in the order 12-Glu <12-G8G-12 < 12-G5G-12 < 12-G2G-12. In
      the three gemini surfactant systems, the decreased spacer chain length resulted
      in the increased maximum viscosity and elastic modulus of the saturated alpha
      gels at a given water concentration. This is caused by the decreased amount of
      excess water being present outside the alpha-gel structure (or the increased
      amount of water incorporated between the surfactant-alcohol bilayers). To the
      best of our knowledge, this is the first report focusing on the formation of
      alpha-gel in gemini surfactant systems. 

PMID- 24912110
TI  - A case of sacral hydatid cyst.
AB  - INTRODUCTION: Hydatid cyst of bone constitutes only 0.5-2% of all hydatidoses.
      The thoracic spine is the most common site of spinal hydatidoses. Primary hydatid
      cyst of the sacral spinal canal is rare. PRESENTATION OF CASE: A 19-year-old man
      had cauda equina syndrome with pelvic pain 15 days ago, the pelvic radiography
      shows a lytic image depend on the left sacral wing. MRI showed an intra-pelvic
      cystic image invading the sacrum T1 hypointense and T2W hyperintense. The Hydatid
      serology was positive.Surgical treatment consisted of a wide drainage of hydatid
      cavity dug in the left sacral wing, and by which it communicated intra pelvic,
      with removal of the entire cyst by gentle aspiration, abundant rinsing with
      hypertonic saline, release and sacred roots encompassed in a puddle of fibrosis
      hydatid.The evolution was good with recovery of perineal sensation and anal tone.
      The sacroiliac joint was considered stable and did not require synthesis or
      reconstruction. DISCUSSION: Hydatid cysts predominantly occur in liver and lungs.
      Involvement of other organs is uncommon. Neither surgery nor medical therapy is
      generally effective for bone, especially spinal hydatidosis. The initial
      treatment of choice is surgical excision for neural decompression and
      establishing diagnosis. Albendazole is the drug of choice against this disease,
      when suspected, presurgical use of Albendazole in Echinococcus infestations
      reduces risk of recurrence and/or facilitates surgery by reducing intracystic
      pressure. CONCLUSION: A missed diagnosis of hydatid cyst could be devastating.
      Hence, hydatid cyst should be kept as a differential diagnosis, when encountered
      with a cystic lesion of sacrum. In addition, longterm follow-up is mandatory as
      recurrence is high despite use scolicidal agents.

PMID- 24912112
TI  - Cutaneous alternariosis--a case series of an increasing phaeohyphomycosis.

PMID- 24912113
TI  - Long-term air pollution exposure and diabetes in a population-based Swiss cohort.
AB  - Air pollution is an important risk factor for global burden of disease. There has
      been recent interest in its possible role in the etiology of diabetes mellitus.
      Experimental evidence is suggestive, but epidemiological evidence is limited and
      mixed. We therefore explored the association between air pollution and prevalent
      diabetes, in a population-based Swiss cohort. We did cross-sectional analyses of
      6392 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart
      Diseases in Adults [SAPALDIA], aged between 29 and 73 years. We used estimates of
      average individual home outdoor PM10 [particulate matter <10MUm in diameter] and
      NO2 [nitrogen dioxide] exposure over the 10 years preceding the survey. Their
      association with diabetes was modeled using mixed logistic regression models,
      including participants' study area as random effect, with incremental adjustment
      for confounders. There were 315 cases of diabetes (prevalence: 5.5% [95%
      confidence interval (CI): 2.8, 7.2%]). Both PM10 and NO2 were associated with
      prevalent diabetes with respective odds ratios of 1.40 [95% CI: 1.17, 1.67] and
      1.19 [95% CI: 1.03, 1.38] per 10MUg/m(3) increase in the average home outdoor
      level. Associations with PM10 were generally stronger than with NO2, even in the
      two-pollutant model. There was some indication that beta blockers mitigated the
      effect of PM10. The associations remained stable across different sensitivity
      analyses. Our study adds to the evidence that long term air pollution exposure is
      associated with diabetes mellitus. PM10 appears to be a useful marker of aspects
      of air pollution relevant for diabetes. This association can be observed at
      concentrations below air quality guidelines.

PMID- 24912114
TI  - Vascular endothelial growth factor in a recipient cornea acts as a prognostic
      factor for corneal graft reaction development.
AB  - PURPOSE: To evaluate whether the vascular endothelial growth factor A (VEGF-A) in
      the recipient cornea measured at the time of penetrating keratoplasty (PK) can
      act as a prognostic factor for corneal graft reaction development. METHODS: The
      study included 25 eyes (of 25 patients) scheduled for PK. According to
      preoperative clinical finding, patients were divided into three groups:
      inflammatory with neovascularization (n = 11); inflammatory without
      neovascularization (n = 7); and non-inflammatory (n = 7). One half of the
      recipient cornea was analyzed for the levels of VEGF-A protein using a commercial
      enzyme-linked immunosorbent assay; the other half was analyzed to determine the
      loci of VEGF-A production by immunohistochemistry. The frequencies of corneal
      graft reaction and rejection were recorded, together with the improvement of
      visual acuity. Twenty-five donor corneas obtained from cadaver eyes represented
      the control group (n = 25). RESULTS: There was a statistically significant
      difference in the levels of VEGF-A protein between the recipient corneal buttons
      obtained from eyes with inflammatory changes and neovascularization, and those
      from the non-inflammatory group and controls (p < 0.01). The level of VEGF-A was
      287.74 pg/ml (standard deviation [SD] = 129.181) in the inflammatory with corneal
      neovascularization group, 227.64 pg/ml (SD = 85.590) in the inflammatory without
      neovascularization group, 115.37 pg/ml (SD = 105.93) in the non-inflammatory
      group, and 142.28 pg/ml (SD = 93.081) in the control group. Graft
      reaction/rejection rate was 54.5%/45.5% in the inflammatory with
      neovascularization group, 14.3%/0% in the inflammatory without neovascularization
      group, and 14.3%/14.3% in non-inflammatory group. Patients who developed clinical
      signs of graft reaction during the postoperative follow-up had a significantly
      higher level of VEGF-A (307.4 pg/ml, SD = 100.058) compared with those without
      any signs of graft reaction (182.8 pg/ml, SD = 124.987). CONCLUSION: Our results
      suggest that both graft reaction and final graft rejection occur more often in
      patients with increased levels of VEGF-A in a recipient cornea at the time of PK.

PMID- 24912115
TI  - TiO2 nanoparticles act as a carrier of Cd bioaccumulation in the ciliate
      Tetrahymena thermophila.
AB  - When nanoparticles can enter a unicellular organism directly, how may they affect
      the bioaccumulation and toxicity of other pollutants already present in the
      environment? To answer this question, we conducted experiments with a protozoan
      Tetrahymena thermophila. The well-dispersed polyacrylate-coated TiO2
      nanoparticles (PAA-TiO2-NPs) were used as a representative nanomaterial, and Cd
      as a conventional pollutant. We found that PAA-TiO2-NPs could get into
      Tetrahymena cells directly. Such internalization was first induced by low
      concentrations of Cd, but later suppressed when Cd concentrations were higher
      than 1 MUg/L. Considering its significant adsorption on PAA-TiO2-NPs, Cd could be
      taken up by T. thermophila in the form of free ion or metal-nanoparticle
      complexes. The latter route accounted for 46.3% of Cd internalization. During the
      5 h depuration period, 4.34-22.1% of Cd was excreted out, which was independent
      of the concentrations of intracellular Cd and PAA-TiO2-NPs. On the other hand,
      both free and intracellular Cd concentrations only partly predicted its toxicity
      at different levels of PAA-TiO2-NPs. This may have resulted from PAA-TiO2-NPs'
      synergistic effects and the distinct subcellular distribution of Cd taken up via
      the two routes above. Overall, we should pay attention to the carrier effects of
      nanoparticles when assessing their environmental risks. 

PMID- 24912116
TI  - The impact of tumor stroma on drug response in breast cancer.
AB  - In the last two decades the breast cancer mortality rate has steadily declined,
      in part, due to the availability of better treatment options. However, drug
      resistance still remains a major challenge. Resistance can be an inherent feature
      of breast cancer cells, but can also arise from the tumor microenvironment. This
      review aims to focus on the modulatory effect of the tumor microenvironment on
      the differing response of breast cancer subtypes to targeted drugs and
      chemotherapy. 

PMID- 24912117
TI  - Polyphenols from the stems of Morus alba and their inhibitory activity against
      nitric oxide production by lipopolysaccharide-activated microglia.
AB  - Neuroinflammatory processes are involved in the pathogenesis of many
      neurodegenerative disorders. Microglial cells, the main immune cells of the
      central nervous system, represent a target of interest to search for naturally
      occurring anti-inflammatory products. In this study, we evaluated the anti
      inflammatory properties of polyphenols obtained from the stems of Morus alba.
      This edible species, known as white mulberry, is frequently studied because of
      its traditional use in Asian medicine and its richness in different types of
      polyphenols, some of which are known to be phytoalexins. One new coumarin
      glycoside, isoscopoletin 6-(6-O-beta-apiofuranosyl-beta-glucopyranoside) (1) was
      mainly isolated by CPC (centrifugal partition chromatography) from this plant,
      together with seven known polyphenols (2-8). Their structures were established on
      the basis of spectroscopic analyses including extensive 2D NMR studies. The eight
      isolated compounds were evaluated for their inhibitory activities on nitric oxide
      (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. The
      absence of cell toxicity is checked by a MTT assay. 

PMID- 24912118
TI  - Intraoperative fluoroscopy, portable X-ray, and CT: patient and operating room
      personnel radiation exposure in spinal surgery.
AB  - BACKGROUND CONTEXT: Intraoperative imaging is essential in spinal surgery to both
      determine the correct level and place implants safely. Surgeons have a variety of
      options: C-arm fluoroscopy (C-arm), portable X-ray (XR) radiography, and portable
      cone-beam computed tomography (O-arm). Although these modalities have their
      respective advantages and disadvantages, direct comparison of radiation exposure
      to either the patient or the operating room (OR) staff has not been made.
      PURPOSE: To determine the amount of radiation exposure to patients and OR staff
      during spine surgery with C-arm, XR, and O-arm. STUDY DESIGN: An experimental
      model to assess radiation exposure to OR staff and phantom patient during spine
      surgery. METHODS: A plastic phantom was created to emulate patient volume and
      absorption scattering characteristics of a typical sized adult abdominal volume.
      Radiation exposure was measured with ion chamber dosimeters to determine entrance
      phantom and scatter exposures at common positions occupied by OR staff for C-arm,
      XR, and O-arm in typical image acquisition during spinal surgery. RESULTS: Single
      lateral (LAT)/posterior-anterior entrance patient radiation exposure for C-arm
      was on average 116/102 mR, single-exposure XR for LAT/anterior-posterior (AP) was
      3,435/2,160 mR, and single-exposure O-arm for LAT/AP was 4,360/5,220 mR. O-arm
      surface exposure LAT/AP was equivalent to 38/41 C-arm and 1.5/2.4 XR exposures.
      The surgeon and surgeon assistant had higher levels of scatter radiation for C
      arm, followed by O-arm and XR. For the LAT C-arm acquisition, a 7.7-fold increase
      in radiation exposure was measured on the X-ray tube side compared with the
      detector side. The anesthesiologist scatter radiation level for a single
      acquisition was highest for O-arm, followed by XR and C-arm. The radiologic
      technologist scatter radiation level was highest for XR, followed by O-arm and
      fluoroscopy. Overall radiation exposure to OR staff was less than 4.4 mR for a
      single acquisition in all modalities. CONCLUSIONS: Assessment of radiation risk
      to the patient and OR staff should be part of the decision for utilization of any
      specific imaging modality during spinal surgery. This study provides the surgeon
      with information to better weigh the risks and benefits of each imaging modality.

PMID- 24912119
TI  - Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and
      suppression of pro-inflammatory cytokines in the epidural compartment after
      intervertebral disc extrusion in a canine model.
AB  - BACKGROUND CONTEXT: In canine intervertebral disc (IVD) disease, a useful animal
      model, only little is known about the inflammatory response in the epidural
      space. PURPOSE: To determine messenger RNA (mRNA) expressions of selected
      cytokines, chemokines, and matrix metalloproteinases (MMPs) qualitatively and
      semiquantitatively over the course of the disease and to correlate results to
      neurologic status and outcome. STUDY DESIGN/SETTING: Prospective study using
      extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE:
      Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES: Duration of
      neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome
      were recorded. After diagnostic imaging, decompressive surgery was performed.
      METHODS: Messenger RNA expressions of interleukin (IL)-1beta, IL-2, IL-4, IL-6,
      IL-8, IL-10, tumor necrosis factor (TNF), interferon (IFN)gamma, MMP-2, MMP-9,
      chemokine ligand (CCL)2, CCL3, and three housekeeping genes was determined in the
      collected epidural material by Panomics 2.0 QuantiGene Plex technology. Relative
      mRNA expression and fold changes were calculated. Relative mRNA expression was
      correlated statistically to clinical parameters. RESULTS: Fold changes of TNF, IL
      1beta, IL-2, IL-4, IL-6, IL-10, IFNgamma, and CCL3 were clearly downregulated in
      all stages of the disease. MMP-9 was downregulated in the acute stage and
      upregulated in the subacute and chronic phase. Interleukin-8 was upregulated in
      acute cases. MMP-2 showed mild and CCL2 strong upregulation over the whole course
      of the disease. In dogs with severe pain, CCL3 and IFNgamma were significantly
      higher compared with dogs without pain (p=.017/.020). Dogs pretreated with
      nonsteroidal anti-inflammatory drugs revealed significantly lower mRNA expression
      of IL-8 (p=.017). CONCLUSIONS: The high CCL2 levels and upregulated MMPs combined
      with downregulated T-cell cytokines and suppressed pro-inflammatory genes in
      extruded canine disc material indicate that the epidural reaction is dominated by
      infiltrating monocytes differentiating into macrophages with tissue remodeling
      functions. These results will help to understand the pathogenic processes
      representing the basis for novel therapeutic approaches. The canine IVD disease
      model will be rewarding in this process.

PMID- 24912120
TI  - The pattern of blood loss in adolescent idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: Previous studies have shown that modern intraoperative blood
      saving techniques dramatically reduce the allogeneic transfusion requirements in
      surgery for adolescent idiopathic scoliosis (AIS). No studies have looked at the
      pattern of postoperative hemoglobin (Hb) in AIS patients undergoing corrective
      spinal surgery and correlated this with the timing of allogeneic transfusion.
      PURPOSE: To describe the pattern of perioperative blood loss in instrumented
      surgery for AIS. We look at the recommendations regarding an ideal preoperative
      Hb, the need for preoperative cross-matching, and the timing of postoperative Hb
      analysis. STUDY DESIGN: This was a retrospective case series. Surgeries were
      performed by one of four substantive pediatric spinal surgeons within a single
      regional center over a 3-year period. PATIENT SAMPLE: A consecutive series of 86
      patients who underwent posterior instrumented fusion for AIS were included: 10
      males and 76 females. Mean age was 14 years (range 10-17 years). All patients had
      posterior instrumented fusion using various blood-saving techniques (eg, cell
      saver). All patients were cross-matched preoperatively, and our transfusion
      trigger value (TTV) was 7 g/dL. OUTCOME MEASURES: Hemoglobin level was the
      outcome measure. Hemoglobin readings were obtained preoperatively, within 2 hours
      of surgery, and daily up to 5 days after surgery. This physiologic measure was
      assessed using routine blood sampling techniques and standardized laboratory
      processing. METHODS: Patient predictor variables (demographic and surgical) were
      assessed for association with Hb levels in a hierarchical model, with repeated Hb
      readings at the lower level being clustered within an individual patient at the
      upper level of the structure. The variation of Hb levels within individuals was
      compared with mean levels in different individuals via the variance partition
      coefficient of the model structure. RESULTS: No patients required intraoperative
      allogeneic transfusion. Only four patients (4.65%) received allogeneic
      transfusion, all within 2 days of surgery. A clinically important drop in Hb
      occurred within the first 2 postoperative days, rising thereafter. The average
      postoperative drop in Hb was 4.1 g/dL. Young males had lower postoperative Hb
      values. Neither the preoperative curve magnitude (Cobb angle of major curve) nor
      the number of vertebrae/levels fused significantly affected the blood loss.
      CONCLUSIONS: We recommend setting a minimum preoperative Hb value that is 5 g/dL
      higher than your TTV. Because no patients required an intraoperative transfusion
      when using modern blood-saving techniques, preoperative cross-matching is
      unnecessary and potentially wasteful of blood reserves. Hemoglobin analysis
      beyond the second postoperative day is unnecessary unless clinically indicated.

PMID- 24912121
TI  - Evaluation of scoring systems and prognostic factors in patients with spinal
      metastases from nasopharyngeal carcinoma.
AB  - BACKGROUND CONTEXT: The decision for operative treatment of patients with spinal
      metastases is dependent on the patient's predicted survival. Tokuhashi, Tomita,
      Bauer, and Oswestry scores have been devised for survival prediction; however,
      none of these systems have been evaluated in nasopharyngeal carcinoma (NPC).
      PURPOSE: To investigate the accuracy of these scoring systems in predicting
      survival and to identify prognostic factors for survival of the patients with
      spinal metastases from NPC. STUDY DESIGN: Retrospective analysis of the patients
      with spinal metastases from NPC who were treated in our institution. PATIENT
      SAMPLE: The study included 87 patients with spinal metastases from NPC. OUTCOME
      MEASURES: The primary outcome measure was the survival time of these patients.
      The potential prognostic factors that are known to influence survival such as
      general condition, extraspinal bone metastases, vertebral bone metastases,
      visceral metastases, and neurologic assessment based on Frankel score were also
      studied. METHODS: The predicted survival according to the four scoring systems
      were calculated and labeled as "A" scores. These patients were then rescored by
      assigning NPC as a good prognostic tumor and labeled as "B" scores. The predicted
      survival of scores A and B were compared with actual survival. Potential
      prognostic factors of survival were investigated using univariate and
      multivariate Cox regression analyses. For all scoring systems, Kaplan-Meier
      survival estimates and log-rank tests were done; the predictive values were
      calculated using postestimation after Cox regression analyses. RESULTS: The
      median overall survival for the whole cohort was 13 (range 1-120) months. In
      multivariate analysis, general condition (p<.01), visceral metastases (p<.01),
      and vertebral metastases (p<.01) showed significant association with survival.
      The absolute score of all scoring systems was significantly associated with
      actual survival, which extended to the different prognostic subgroups of each
      scoring systems. Log-rank test revealed significant differences in survival
      between the different prognostic subgroups of all scoring systems (p<.01).
      Predictive value of survival by modified Tokuhashi score was the highest among
      all four scoring systems. CONCLUSIONS: Patients with spinal metastases from NPC
      have relatively good survival prognosis. All four scoring systems could be used
      to prognosticate these patients. The modified Tokuhashi score is the best in
      doing so.

PMID- 24912122
TI  - Cortistatin is endogenous to the human intervertebral disc and exerts in vitro
      mitogenic effects on annulus cells and a downregulatory effect on TNF-alpha
      expression.
AB  - BACKGROUND CONTEXT: Cortistatin (CST) is a recently discovered cyclic
      neuropeptide with biologic anti-inflammatory properties relevant to disc
      degeneration. PURPOSE: To test whether CST is present in the disc tissue, whether
      its expression is influenced by tumor necrosis factor-alpha (TNF-alpha), and
      whether it influences cell proliferation. STUDY DESIGN: Institutional review
      board-approved study using immunohistochemistry on human disc tissue, in vitro
      annulus cultures to determine the effect of CST on cell proliferation, and the
      effect of TNF-alpha on CST gene expression. PATIENT SAMPLE: Discs from 12
      subjects used for immunohistochemistry, four annulus specimens used for cell
      culture with proinflammatory cytokines, and 11 used for cell proliferation
      analyses. OUTCOME MEASURES: Immunohistochemical localization of CST, gene
      expression of CST, and cell proliferation analyses. METHODS: Immunohistochemistry
      localized CST in disc tissue. Microarray analysis measured CST gene expression.
      Human annulus cells were exposed to CST for proliferation tests or cultured for
      the effect of TNF-alpha on CST expression. Standard statistical analyses were
      performed. RESULTS: Immunohistochemistry identified CST in outer annulus, inner
      annulus, and nucleus tissue. Annulus cells exposed to TNF-alpha revealed
      significantly lower CST expression (p=.013). Exposure to CST significantly
      increased proliferation. Quantitative real-time polymerase chain reaction also
      confirmed expression of CST in vitro. CONCLUSIONS: Data provide the first
      evidence that CST is present in the human disc. Addition of CST significantly
      increased cell proliferation. Cortistatin expression was significantly
      downregulated by TNF-alpha exposure in vitro. Findings suggest possible in vivo
      reduction of the anti-inflammatory actions of CST because of elevated
      proinflammatory cytokines during degenerating disc.

PMID- 24912124
TI  - Can we learn from heterosis and epigenetics to improve photosynthesis?
AB  - Heterosis is the increase in fitness and yield of F1 hybrids derived from a cross
      between distantly related genotypes. The use of heterosis is one of the most
      successful crop breeding strategies, but the underlying molecular mechanisms are
      still poorly defined. There is ample evidence that heterosis is associated with
      increased rates of photosynthesis and recent analyses have shed light on the
      underlying biochemical principles. In parallel, the importance of epigenetic
      chromatin modifications in heterosis has now been established. The first direct
      links between epigenetic changes and improved photosynthesis have also been
      demonstrated. As epigenetic engineering is now possible, we discuss the
      feasibility of altering the epigenetic code to enhance photosynthesis. 

PMID- 24912125
TI  - Plant carotenoids: genomics meets multi-gene engineering.
AB  - Carotenoids are present in plant photosynthetic tissues, where they have
      essential roles in photoreception and photoprotection, as well as in non
      photosynthetic tissues, where they act as colorants, precursors for plant
      isoprenoid volatiles and signaling molecules (abscisic acid and strigolactones),
      nutritional antioxidants and vitamin A precursors. This review presents the
      recent advances in our understanding of their biosynthesis, the key metabolic
      steps controlling their accumulation in plant non-photosynthetic tissues and
      their metabolic engineering using multi-gene approaches. 

PMID- 24912126
TI  - Andrographis paniculata: a critical appraisal of extraction, isolation and
      quantification of andrographolide and other active constituents.
AB  - Andrographispaniculata, referred to as 'Kalmegh' in ancient texts, is regarded as
      a nostrum of the modern world. Oral administration of the leaves of this plant is
      effective in the treatment of upper respiratory tract infections, liver toxicity
      and a variety of other ailments. The practices of adulteration in the original
      material of this drug have made it imperative to develop techniques to verify the
      authenticity of the products of this plant for quality assurance.
      Andrographolide, a bitter diterpenoid, is the major active principle present in
      the plant, and therefore its determination and quantification in the plant
      extracts are important. This article provides a detailed account of various
      extraction and chromatographic techniques used for the identification, isolation
      and quantification of the various active principles of A. paniculata.
      Pharmacological properties and phytochemistry of this plant and the physico
      chemical properties of these bio-compounds have also been outlined. 

PMID- 24912127
TI  - The prevalence of gestational diabetes mellitus among Aboriginal and Torres
      Strait Islander women in Australia: a systematic review and meta-analysis.
AB  - INTRODUCTION: Gestational diabetes mellitus (GDM) is an important and increasing
      health problem. This study aims to investigate and explain the marked variation
      in reported GDM prevalence among Australian Indigenous women. MATERIALS AND
      METHODS: We searched five databases to August 2013 for studies of GDM prevalence;
      two people independently assessed search results, extracted data, and appraised
      risk of bias. Meta-analysis was conducted, and between-study heterogeneity
      examined using subgroup analyses. Within-study findings were synthesized
      narratively. RESULTS: The pooled GDM prevalence from 23 of the 25 total studies
      (5.74%, 4.78-6.71) was similar to that reported in national studies, but
      heterogeneity was substantial (I(2)  = 97%), making conclusions from between
      study comparisons difficult. The greatest reductions in heterogeneity were seen
      within subgroups using localized diagnostic criteria (I(2)  = 43%, 3 studies),
      universal screening (I(2)  = 58%) and some jurisdictions, probably reflecting
      proxy measures of increased consistency in diagnostic and screening methods.
      Insufficient data were available to assess the effect of factors such as
      rurality, diagnostic criteria, study design and data sources on prevalence.
      Synthesis of within-study findings showed: higher age-adjusted prevalences of GDM
      in Indigenous versus non-Indigenous women; Indigenous women have greater
      increases in prevalence with maternal age; and non-Indigenous women appear to
      have a steeper increase in GDM prevalence over time. Prevalence increased almost
      fourfold in two studies following introduction of universal screening when
      compared with selective risk-based screening, although numbers were small.
      DISCUSSION/CONCLUSIONS: The published GDM prevalence among Indigenous women
      varies markedly, probably due to variation in diagnostic and screening practices.

PMID- 24912128
TI  - Density functional theory study of the conformation and optical properties of
      hybrid Au(n)-dithienylethene systems (n = 3, 19, 25).
AB  - We present a theoretical study of Aun-dithienylethene hybrid systems (n = 3, 19,
      25), where the organic molecule is covalently linked to a nanometer-scaled gold
      nanoparticle (NP). We aim at gaining insights on the optical properties of such
      photochromic devices and proposing a size-limited gold aggregate model able to
      recover the optical properties of the experimental system. We thus present a DFT
      based calculation scheme to model the ground-state (conformation, energetic
      parameters) and excited-state properties (UV-visible absorption spectra) of this
      type of hybrid systems. Within this framework, the structural parameters
      (adsorption site, orientation, and internal structure of the photochrome) are
      found to be slightly dependent on the size/shape of the gold aggregate. The
      influence of the gold fragment on the optical properties of the resulting hybrid
      system is then discussed with the help of TD-DFT combined with an analysis of the
      virtual orbitals involved in the photochromic transitions. We show that, for the
      open hybrid isomer, the number of gold atoms is the key parameter to recover the
      photoactive properties that are experimentally observed. On the contrary, for
      hybrid closed systems, the three-dimensional structure of the metallic aggregate
      is of high impact. We thus conclude that Au25 corresponds to the most appropriate
      fragment to model nanometer-sized NP-DTE hybrid device. 

PMID- 24912129
TI  - Influence of lipoic acid on testicular toxicity induced by bi-n-butyl phthalate
      in rats.
AB  - Bi-n-butyl phthalate (BNBP) is an environmental pollutant. The aim of this study
      was to evaluate the protective effect of lipoic acid (LA) against testicular
      dysfunction associated with the intake of to BNBP- intoxicated rats. Adult male
      Wistar rats were divided into 4 groups of 6 animals each, and received medication
      orally for 14 days. Group I rats received 0.5 ml corn oil. Group II rats received
      LA (20 mg/kg B.W./day). Group III rats received BNBP (250 mg/kg B.W./day). Group
      IV rats received LA 24h prior to BNBP intake. Testes weight, cauda sperm count
      and sperm motility were decreased significantly by 18.15%, 13.83% and 13.5%,
      respectively, after BNBP treatment. Significant increase by 12.1%, 10.20% and
      11.51%, respectively, was observed in LA-BNBP rats. Significant increase by
      1.53%, 1.5% and 1.8%, for serum follicle stimulating hormone, testosterone and
      total antioxidant status, respectively, were observed in LA-BNBP rats. Testicular
      lipid peroxides and lactate dehydrogenase enzyme were significantly decreased by
      1.5 and 1.6 folds, respectively, in LA-BNBP rats were decreased after BNBP
      treatment. Testicular superoxide dismutase, catalase and glutathione reductase
      enzymes were significantly increased in LA-BNBP rats. LA-BNBP rats, decreased the
      damage to seminiferous tubules produced by BNBP intake. In conclusion, LA
      mitigated BNBP-induced testicular toxicity through antioxidant mechanism and by
      direct free radical scavenging activity.

PMID- 24912130
TI  - Phytoplankton succession affects the composition of Polynucleobacter subtypes in
      humic lakes.
AB  - Phytoplankton influence the composition of bacterial communities, but the
      taxonomic specificity of algal-bacterial interactions is unclear due to the
      aggregation of ecologically distinct bacterial populations by community
      characterization methods. Here we examine whether phytoplankton seasonal
      succession affects the composition of subtypes within the cosmopolitan freshwater
      bacterial genus Polynucleobacter. Changes in the composition of Polynucleobacter
      subtypes were characterized in samples collected weekly from May to August in
      2003 and 2008 from three humic lakes using terminal restriction fragment length
      polymorphism fingerprinting of the protein-encoding cytochrome c oxidase ccoN
      gene. Changes in phytoplankton population abundances explained, on average, 30%
      of temporal variation in the composition of Polynucleobacter subtypes and the
      interaction between phytoplankton and the environment explained an additional 18%
      of temporal variation. The effect of phytoplankton on specific Polynucleobacter
      subtypes was experimentally confirmed by changes in Polynucleobacter subtype
      composition following incubation with different phytoplankton assemblages or a no
      phytoplankton control. Phytoplankton-associated subtypes and differentiation in
      substrate use among subtypes likely contribute to the effects of phytoplankton on
      Polynucleobacter subtype composition. Interactions between unique
      Polynucleobacter populations and phytoplankton highlight the ecological
      significance and specificity of species interactions in freshwater communities. 

PMID- 24912131
TI  - Brain natriuretic peptide and C-type natriuretic peptide maintain porcine oocyte
      meiotic arrest.
AB  - Recent studies have shown that C-type natriuretic peptide (CNP) serves as a key
      control system during mouse oocyte maturation. We used pig models (in vitro and
      in vivo) to explore the role played by the natriuretic peptide family in porcine
      oocyte maturation. We reported the expression and location of natriuretic peptide
      system in different stages of porcine antral follicles. Atrial natriuretic
      peptide (ANP) and CNP were expressed primarily in granulosa cells, whereas brain
      natriuretic peptide (BNP) and natriuretic peptide receptor-B (NPRB) receptor were
      expressed in granulosa cells (both cumulus and mural granulosa cells) and thecal
      internal cells, and the natriuretic peptide receptor-A (NPRA) receptor
      predominantly in thecal cells. Upon in vitro culture, BNP and CNP maintained
      meiotic arrest of oocytes associated with cumulus cells. The expression levels of
      BNP, CNP, and the NPRB receptor increased upon treatment of prepubertal gilts
      with pregnant mare's serum gonadotropin and decreased upon subsequent human
      chorionic gonadotropin injection. Such dynamic changes in the expression of
      natriuretic peptides and their receptor paralleled the proportions of oocytes
      exhibiting nuclear maturation in vivo. These data indicated that BNP and CNP co
      contributed to maintaining porcine meiotic arrest under physiological condition
      and lutenizing hormone (LH) relieved this inhibitory effect by decreasing the
      expression levels of BNP and CNP in vivo. Our present work, combined with
      previous data, improved the understanding of the oocyte meiotic arrest mechanisms
      and further revealed that natriuretic peptides serve as oocyte maturation
      inhibitor (OMI) to inhibit oocyte maturation in mammals.

PMID- 24912132
TI  - Nonreductive chemical release of intact N-glycans for subsequent labeling and
      analysis by mass spectrometry.
AB  - A novel strategy is proposed, using cost-saving chemical reactions to generate
      intact free reducing N-glycans and their fluorescent derivatives from
      glycoproteins for subsequent analysis. N-Glycans without core alpha-1,3-linked
      fucose are released in reducing form by selective hydrolysis of the N-type
      carbohydrate-peptide bond of glycoproteins under a set of optimized mild alkaline
      conditions and are comparable to those released by commonly used peptide-N
      glycosidase (PNGase) F in terms of yield without any detectable side reaction
      (peeling or deacetylation). The obtained reducing glycans can be routinely
      derivatized with 2-aminobenzoic acid (2-AA), 1-phenyl-3-methyl-5-pyrazolone
      (PMP), and potentially some other fluorescent reagents for comprehensive
      analysis. Alternatively, the core alpha-1,3-fucosylated N-glycans are released in
      mild alkaline medium and derivatized with PMP in situ, and their yields are
      comparable to those obtained using commonly used PNGase A without conspicuous
      peeling reaction or any detectable deacetylation. Using this new technique, the N
      glycans of a series of purified glycoproteins and complex biological samples were
      successfully released and analyzed by electrospray ionization mass spectrometry
      (ESI-MS) and tandem mass spectrometry (MS/MS), demonstrating its general
      applicability to glycomic studies. 

PMID- 24912133
TI  - Statins and activity: proceed with caution.

PMID- 24912134
TI  - Macronutrient selection by seven inbred mouse strains and three taste-related
      knockout strains.
AB  - Many animals thrive when given a choice of separate sources of macronutrients.
      How they do this is unknown. Here, we report some studies comparing the
      spontaneous choices between carbohydrate- and fat-containing food sources of
      seven inbred mouse strains (B6, BTBR, CBA, JF1, NZW, PWD and PWK) and three mouse
      models with genetic ablation of taste transduction components (T1R3, ITPR3 and
      CALHM1). For 8days, each mouse could choose between sources of carbohydrate (CHO
      P; sucrose-cornstarch) and fat (Fat-P; vegetable shortening) with each source
      also containing protein (casein). We found that the B6 and PWK strains markedly
      preferred the CHO-P diet to the Fat-P diet, the BTBR and JF1 strains markedly
      preferred the Fat-P diet to the CHO-P diet, and the CBA, NZW and PWD strains
      showed equal intakes of the two diets (by weight). Relative to their WT
      littermates, ITPR3 and CALHM1 KO mice had elevated Fat-P preferences but T1R3 KO
      mice did not. There were differences among strains in adaption to the diet choice
      and there were differences in response between males and females on some days.
      These results demonstrate the diverse responses to macronutrients of inbred mice
      and they point to the involvement of chemosensory detectors (but not sweetness)
      as contributors to macronutrient selection. 

PMID- 24912136
TI  - Supertaster, super reactive: oral sensitivity for bitter taste modulates
      emotional approach and avoidance behavior in the affective startle paradigm.
AB  - People differ in both their sensitivity for bitter taste and their tendency to
      respond to emotional stimuli with approach or avoidance. The present study
      investigated the relationship between these sensitivities in an affective picture
      paradigm with startle responding. Emotion-induced changes in arousal and
      attention (pupil modulation), priming of approach and avoidance behavior (startle
      reflex modulation), and subjective evaluations (ratings) were examined.
      Sensitivity for bitter taste was assessed with the 6-n-propylthiouracil (PROP)
      sensitivity test, which discriminated individuals who were highly sensitive to
      PROP compared to NaCl (PROP-tasters) and those who were less sensitive or
      insensitive to the bitter taste of PROP. Neither pupil responses nor picture
      ratings differed between the two taster groups. The startle eye blink response,
      however, significantly differentiated PROP-tasters from PROP-insensitive
      subjects. Facilitated response priming to emotional stimuli emerged in PROP
      tasters but not in PROP-insensitive subjects at shorter startle lead intervals
      (200-300ms between picture onset and startle stimulus onset). At longer lead
      intervals (3-4.5s between picture onset and startle stimulus onset) affective
      startle modulation did not differ between the two taster groups. This implies
      that in PROP-sensitive individuals action tendencies of approach or avoidance are
      primed immediately after emotional stimulus exposure. These results suggest a
      link between PROP taste perception and biologically relevant patterns of
      emotional responding. Direct perception-action links have been proposed to
      underlie motivational priming effects of the startle reflex, and the present
      results extend these to the sensory dimension of taste. 

PMID- 24912135
TI  - Role of spontaneous physical activity in prediction of susceptibility to activity
      based anorexia in male and female rats.
AB  - Anorexia nervosa (AN) is a chronic eating disorder affecting females and males,
      defined by body weight loss, higher physical activity levels and restricted food
      intake. Currently, the commonalities and differences between genders in etiology
      of AN are not well understood. Animal models of AN, such as activity-based
      anorexia (ABA), can be helpful in identifying factors determining individual
      susceptibility to AN. In ABA, rodents are given an access to a running wheel
      while food restricted, resulting in paradoxical increased physical activity
      levels and weight loss. Recent studies suggest that different behavioral traits,
      including voluntary exercise, can predict individual weight loss in ABA. A higher
      inherent drive for movement may promote development and severity of AN, but this
      hypothesis remains untested. In rodents and humans, drive for movement is defined
      as spontaneous physical activity (SPA), which is time spent in low-intensity, non
      volitional movements. In this paper, we show that a profile of body weight
      history and behavioral traits, including SPA, can predict individual weight loss
      caused by ABA in male and female rats with high accuracy. Analysis of the
      influence of SPA on ABA susceptibility in males and females rats suggests that
      either high or low levels of SPA increase the probability of high weight loss in
      ABA, but with larger effects in males compared to females. These results suggest
      that the same behavioral profile can identify individuals at-risk of AN for both
      male and female populations and that SPA has predictive value for susceptibility
      to AN. 

PMID- 24912137
TI  - Protein kinase A mediates adenosine A2a receptor modulation of neurotransmitter
      release via synapsin I phosphorylation in cultured cells from medulla oblongata.
AB  - Synaptic transmission is an essential process for neuron physiology. Such process
      is enabled in part due to modulation of neurotransmitter release. Adenosine is a
      synaptic modulator of neurotransmitter release in the Central Nervous System,
      including neurons of medulla oblongata, where several nuclei are involved with
      neurovegetative reflexes. Adenosine modulates different neurotransmitter systems
      in medulla oblongata, specially glutamate and noradrenaline in the nucleus
      tractussolitarii, which are involved in hypotensive responses. However, the
      intracellular mechanisms involved in this modulation remain unknown. The
      adenosine A2a receptor modulates neurotransmitter release by activating two cAMP
      protein effectors, the protein kinase A and the exchange protein activated by
      cAMP. Therefore, an in vitro approach (cultured cells) was carried out to
      evaluate modulation of neurotransmission by adenosine A2a receptor and the
      signaling intracellular pathway involved. Results show that the adenosine A2a
      receptor agonist, CGS 21680, increases neurotransmitter release, in particular,
      glutamate and noradrenaline and such response is mediated by protein kinase A
      activation, which in turn increased synapsin I phosphorylation. This suggests a
      mechanism of A2aR modulation of neurotransmitter release in cultured cells from
      medulla oblongata of Wistar rats and suggest that protein kinase A mediates this
      modulation of neurotransmitter release via synapsin I phosphorylation. 

PMID- 24912138
TI  - A U-shaped type II contraction pattern in patients with strict left bundle branch
      block predicts super-response to cardiac resynchronization therapy.
AB  - BACKGROUND: New criteria to define strict left bundle branch block (LBBB) on the
      basis of pathophysiological principles predict response to cardiac
      resynchronization therapy (CRT). Heterogeneous activation and contraction
      patterns have been identified in patients with classical LBBB. Cardiac magnetic
      resonance (CMR) imaging has demonstrated that a U-shaped (type II) contraction
      predicts reverse remodeling post-CRT. A homogeneous spread of (type I)
      contraction is less predictive. OBJECTIVES: The purpose of this study was to
      investigate contraction patterns among patients with strict LBBB and to test
      whether a type II contraction pattern better predicts CRT response and super
      response. METHODS: Thirty-seven patients with strict LBBB (QRS duration >=140 ms
      for men and >=130 ms for women with mid-QRS notching or slurring in >=2
      contiguous leads) underwent cine CMR imaging pre-CRT with an analysis of their
      contraction patterns by using endocardial contour tracking software. Patients
      were evaluated for reverse remodeling 6 months postimplantation. RESULTS:
      Nineteen patients (51%) had a type II contraction pattern. A total of 25 patients
      (68%) of the cohort reverse remodeled. In the type II contraction group, all 19
      patients (100%) reverse remodeled as compared with 6 patients (33%) in the type I
      contraction group (P < .01). Super-response was achieved in 21 patients (57%) of
      the total cohort: 5 patients with a type I contraction pattern (28%) and 16
      patients with a type II contraction pattern (84%) (P < .01). CONCLUSION: Patients
      with strict LBBB who are guideline indicated for CRT have heterogeneous
      contraction patterns derived from cine CMR. A type II contraction pattern is
      strongly predictive for reverse remodeling and super-response. This questions
      whether strict LBBB criteria alone are sufficient to reliably predict a positive
      response to CRT.

PMID- 24912139
TI  - P-wave evidence as a method for improving algorithm to detect atrial fibrillation
      in insertable cardiac monitors.
AB  - BACKGROUND: Frequent premature atrial contractions and sick sinus syndrome are
      primary causes of inappropriate atrial fibrillation (AF) detection in insertable
      cardiac monitors (ICMs). OBJECTIVE: The study aimed to validate an algorithm
      designed to reduce inappropriate AF detection on the basis of the identification
      of a single P wave during the cardiac cycle. METHODS: The original detection
      algorithm looks for evidence of AF based on differences in the pattern of R-R
      intervals over a 2-minute period. The improved algorithm reduces evidence for AF
      detection if P waves are detected. The algorithm was validated by using Holter
      data, which collected 2 leads of surface electrocardiogram and continuously
      uplinked ICM electrocardiogram over a 46-hour period. ICM detections were
      compared with Holter annotations to compute episode and duration detection
      performance. RESULTS: Valid Holter recordings (8442 hours) were analyzed from 206
      patients. True AF was observed in 76 patients, yielding 482 true AF episodes >=2
      minutes in duration and 1191 hours of AF. The algorithm correctly identified
      97.8% of the total AF duration and 99.3% of the total sinus or non-AF rhythm
      duration. The algorithm detected 85% (90% per-patient average) of all AF episodes
      >=2 minutes in duration, and 55% (78% per-patient average) of the detected
      episodes had AF. AF was found in 95% of the detected episodes >1 hour. The
      improved algorithm reduced inappropriate episodes and duration by 46% and 55%,
      respectively, while also reducing appropriate episodes and duration by 2% and
      0.1%, respectively. CONCLUSION: An improvement in the ICM algorithm for AF
      detection incorporating P-wave information substantially reduced inappropriately
      detected episodes and duration, with minimal reduction in sensitivity for
      detecting AF.

PMID- 24912140
TI  - Two-year course trajectories of anxiety disorders: do DSM classifications matter?
AB  - OBJECTIVE: Anxiety disorders have been shown to differ in their course, but it is
      unknown whether DSM-categories represent clinically relevant course trajectories.
      We aim to identify anxiety course trajectories using a data-driven method and to
      examine whether these course trajectories correspond to DSM-categories or whether
      other clinical indicators better differentiate them. METHOD: 907 patients with
      panic disorder with agoraphobia, panic disorder without agoraphobia ,
      agoraphobia, social phobia, or generalized anxiety disorder according to DSM-IV
      criteria were derived from a prospective cohort study (Netherlands Study of
      Depression and Anxiety). Baseline data were collected between September 2004 and
      February 2007; follow-up data, between October 2006 and March 2009. Latent class
      growth analysis was conducted, based on symptoms of anxiety and avoidance
      assessed with the Life Chart Interview covering a 2-year time period. Identified
      course trajectories were compared with DSM-IV diagnoses and a wider set of
      predictors. RESULTS: We identified a class with minimal symptoms over time
      (41.7%), a moderately severe chronic class (42.8%), and a severe chronic class
      (15.4%). Panic disorder with agoraphobia (OR = 2.14; 95% CI, 1.48-3.09) and
      social phobia (OR = 1.97; 95% CI, 1.46-2.68) predicted moderately severe
      chronicity; panic disorder with agoraphobia (OR = 2.70; 95% CI, 1.66-4.40),
      social phobia (OR = 2.46; 95% CI, 1.62-3.74), and generalized anxiety disorder
      (OR = 1.86; 95% CI, 1.23-2.82) predicted a severe chronic course. However,
      baseline severity, duration of anxiety, and disability better predicted severe
      chronic course trajectories than DSM-categories. Additionally, partner status,
      age at onset, childhood trauma, and comorbid depressive disorder predicted
      chronic courses. CONCLUSIONS: Course of anxiety was pleomorphic with over 40%
      having a favorable course, thereby questioning the common notion of chronicity of
      anxiety disorders. Severity, duration of anxiety, and disability were able to
      better identify severe chronic course trajectories as compared with DSM-IV
      categories. These findings facilitate the identification of chronic course
      trajectories of anxiety disorders in clinical care and support current debates on
      staging and profiling of mental disorders.

PMID- 24912141
TI  - Enhanced power generation and energy conversion of sewage sludge by CEA-microbial
      fuel cells.
AB  - The production of methane from sewage sludge through the use of anaerobic
      digestion has been able to effectively offset energy costs for wastewater
      treatment. However, significant energy reserves are left unrecovered and effluent
      standards are not met necessitating secondary processes such as aeration. In the
      current study a novel cloth-electrode assembly microbial fuel cell (CEA-MFC) was
      used to generate electricity from sewage sludge. Fermentation pretreatment of the
      sludge effectively increased the COD of the supernatant and improved reactor
      performance. Using the CEA-MFC design, a maximum power density of 1200 mW m(-2)
      was reached after a fermentation pre-treatment time of 96 h. This power density
      represents a 275% increase over those previously observed in MFC systems. Results
      indicate continued improvements are possible and MFCs may be a viable
      modification to existing wastewater treatment infrastructure.

PMID- 24912142
TI  - Secondhand smoke exposure at home: assessment by biomarkers and airborne markers.
AB  - OBJECTIVE: We assessed and characterized the relationship among biomarkers of
      secondhand smoke (SHS) exposure in non-smokers according to their exposure at
      home as measured by airborne markers. METHODS: We conducted an observational
      study on exposure to SHS at home using airborne markers (nicotine and benzene)
      and biomarkers from the non-smokers living in these homes. We selected 49 non
      smoking volunteers from different homes: 25 non-smokers living with at least one
      smoker and 24 non-smokers living in smoke-free homes. We installed two passive
      devices to measure nicotine and benzene concentrations in the main room of the
      house (i.e., the living room). One week later, the researcher returned to the
      volunteer's home to collect the two devices, obtain saliva and urine samples, and
      administer a SHS questionnaire. RESULTS: Salivary and urinary cotinine
      concentrations highly correlated with air nicotine concentrations measured at the
      volunteers'homes (rsp=0.738 and rsp=0.679, respectively). The concentrations of
      airborne markers of SHS and biomarkers in non-smokers increased with increasing
      self-reported intensity and duration of SHS exposure at home during the previous
      week (p<0.05). The multivariable regression model showed a significant
      association with nicotine in air at home (beta=0.126, p=0.002 for saliva and
      beta=0.115, p=0.010 for urine). CONCLUSIONS: Our findings suggest that, even in
      countries with comprehensive smoke-free legislation, exposure to SHS at home
      continues to be the main source of exposure for non-smokers who live in non-smoke
      free homes. Therefore, public health policies should promote smoke-free homes.

PMID- 24912143
TI  - An evolving arsenal: viral RNA detection by RIG-I-like receptors.
AB  - RIG-I-like receptors (RLRs) utilize a specialized, multi-domain architecture to
      detect and respond to invasion by a diverse set of viruses. Structural
      similarities among these receptors provide a general mechanism for double strand
      RNA recognition and signal transduction. However, each RLR has developed unique
      strategies for sensing the specific molecular determinants on subgroups of viral
      RNAs. As a means to circumvent the antiviral response, viruses escape RLR
      detection by degrading, or sequestering or modifying their RNA. Patterns of
      variation in RLR sequence reveal a continuous evolution of the protein domains
      that contribute to RNA recognition and signaling. 

PMID- 24912145
TI  - 3D cell culture systems: advantages and applications.
AB  - Cell cultures are important material of study for the variety of advantages that
      they offer. Both established continuous cell lines and primary cell cultures
      continue to be invaluable for basic research and for direct applications.
      Technological advancements are necessary to address emerging complex challenges
      and the way cells are cultured in vitro is an area of intense activity. One
      important advancement in cell culture techniques has been the introduction of
      three dimensional culture systems. This area is one of the fastest growing
      experimental approaches in life sciences. Augmented with advancements in cell
      imaging and analytical systems, as well as the applications of new scaffolds and
      matrices, cells have been increasingly grown as three dimensional models. Such
      cultures have proven to be closer to in vivo natural systems, thus proving to be
      useful material for many applications. Here, we review the three dimensional way
      of culturing cells, their advantages, the scaffolds and matrices currently
      available, and the applications of such cultures in major areas of life sciences.

PMID- 24912144
TI  - Plasma membrane Ca2+-ATPase regulates Ca2+ signaling and the proliferation of
      airway smooth muscle cells.
AB  - Plasma membrane Ca2+-ATPase (PMCA) plays an important role in regulating
      intracellular Ca2+ homeostasis by extruding excessive Ca2+ to extracellular
      spaces. PMCA has four isoforms and is widely expressed in different tissues and
      cells including airway smooth muscle cells (ASMCs). In the present study, we
      investigated the role of PMCA in the maintenance of Ca2+ homeostasis and
      regulation of ASMCs proliferation. By using Ca2+ fluorescence, we found that
      inhibition of PMCA with LaCl3 or carboxyeosin (CE) decreased the decay rate of
      Ca2+ transient induced by bradykinin (BK). No obvious decay was observed when
      SERCA was inhibited by thapsigargin (TpG). LaCl3 and CE also induced a
      spontaneous [Ca2+]i increase in the presence of TpG even in Ca2+-free bath
      solution. Both LaCl3 and CE inhibited UTP-induced Ca2+ oscillations in ASMCs. PCR
      assay found that PMCA1 and PMCA4 mRNA were expressed in rat ASMCs. The expression
      of PMCA4 was downregulated in proliferating ASMCs when compared to resting cells.
      Both the isoform-nonselective PMCA inhibitor caloxin 2a1 and PMCA4-selective
      inhibitor caloxin 1b1 decreased the decay rate of Ca2+ transient induced by TpG
      or BK. PMCA inhibitors except caloxin 2a1 promoted ASMCs proliferation. Annexin-V
      apoptosis assay detected that caloxin 2a1 increased ASMCs apoptosis, suggesting
      that inhibition of PMCA with different blockers results in different [Ca2+]i and
      thus different cellular response. Our results provide evidences to support the
      hypothesis that PMCA is involved in the regulation of Ca2+ homeostasis and ASMCs
      proliferation. These data suggest that PMCA may be a new target in the treatment
      of chronic asthma.

PMID- 24912146
TI  - Father's brain is sensitive to childcare experiences.
AB  - Although contemporary socio-cultural changes dramatically increased fathers'
      involvement in childrearing, little is known about the brain basis of human
      fatherhood, its comparability with the maternal brain, and its sensitivity to
      caregiving experiences. We measured parental brain response to infant stimuli
      using functional MRI, oxytocin, and parenting behavior in three groups of parents
      (n = 89) raising their firstborn infant: heterosexual primary-caregiving mothers
      (PC-Mothers), heterosexual secondary-caregiving fathers (SC-Fathers), and primary
      caregiving homosexual fathers (PC-Fathers) rearing infants without maternal
      involvement. Results revealed that parenting implemented a global "parental
      caregiving" neural network, mainly consistent across parents, which integrated
      functioning of two systems: the emotional processing network including
      subcortical and paralimbic structures associated with vigilance, salience,
      reward, and motivation, and mentalizing network involving frontopolar-medial
      prefrontal and temporo-parietal circuits implicated in social understanding and
      cognitive empathy. These networks work in concert to imbue infant care with
      emotional salience, attune with the infant state, and plan adequate parenting. PC
      Mothers showed greater activation in emotion processing structures, correlated
      with oxytocin and parent-infant synchrony, whereas SC-Fathers displayed greater
      activation in cortical circuits, associated with oxytocin and parenting. PC
      Fathers exhibited high amygdala activation similar to PC-Mothers, alongside high
      activation of superior temporal sulcus (STS) comparable to SC-Fathers, and
      functional connectivity between amygdala and STS. Among all fathers, time spent
      in direct childcare was linked with the degree of amygdala-STS connectivity.
      Findings underscore the common neural basis of maternal and paternal care, chart
      brain-hormone-behavior pathways that support parenthood, and specify mechanisms
      of brain malleability with caregiving experiences in human fathers. 

PMID- 24912147
TI  - Microscopic insights into the protein-stabilizing effect of trimethylamine N
      oxide (TMAO).
AB  - Although it is widely known that trimethylamine N-oxide (TMAO), an osmolyte used
      by nature, stabilizes the folded state of proteins, the underlying mechanism of
      action is not entirely understood. To gain further insight into this important
      biological phenomenon, we use the C=N stretching vibration of an unnatural amino
      acid, p-cyano-phenylalanine, to directly probe how TMAO affects the hydration and
      conformational dynamics of a model peptide and a small protein. By assessing how
      the lineshape and spectral diffusion properties of this vibration change with
      cosolvent conditions, we are able to show that TMAO achieves its protein
      stabilizing ability through the combination of (at least) two mechanisms: (i) It
      decreases the hydrogen bonding ability of water and hence the stability of the
      unfolded state, and (ii) it acts as a molecular crowder, as suggested by a recent
      computational study, that can increase the stability of the folded state via the
      excluded volume effect. 

PMID- 24912148
TI  - Identification of genes preventing transgenerational transmission of stress
      induced epigenetic states.
AB  - Examples of transgenerational transmission of environmentally induced epigenetic
      traits remain rare and disputed. Abiotic stress can release the transcription of
      epigenetically suppressed transposons and, noticeably, this activation is only
      transient. Therefore, it is likely that mechanisms countering the mitotic and
      meiotic inheritance of stress-triggered chromatin changes must exist but are
      undefined. To reveal these mechanisms, we screened for Arabidopsis mutants
      impaired in the resetting of stress-induced loss of epigenetic silencing and
      found that two chromatin regulators, Decrease in DNA methylation1 (DDM1) and
      Morpheus' Molecule1 (MOM1), act redundantly to restore prestress state and thus
      erase "epigenetic stress memory". In ddm1 mutants, stress hyperactivates
      heterochromatic transcription and transcription persists longer than in the wild
      type. However, this newly acquired state is not transmitted to the progeny.
      Strikingly, although stress-induced transcription in mom1 mutants is as rapidly
      silenced as in wild type, in ddm1 mom1 double mutants, transcriptional signatures
      of stress are able to persist and are found in the progeny of plants stressed as
      small seedlings. Our results reveal an important, previously unidentified
      function of DDM1 and MOM1 in rapid resetting of stress induced epigenetic states,
      and therefore also in preventing their mitotic propagation and transgenerational
      inheritance. 

PMID- 24912149
TI  - Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives.
AB  - The voltage-gated proton channel Hv1 plays important roles in proton extrusion,
      pH homeostasis, and production of reactive oxygen species in a variety of cell
      types. Excessive Hv1 activity increases proliferation and invasiveness in cancer
      cells and worsens brain damage in ischemic stroke. The channel is composed of two
      subunits, each containing a proton-permeable voltage-sensing domain (VSD) and
      lacking the pore domain typical of other voltage-gated ion channels. We have
      previously shown that the compound 2-guanidinobenzimidazole (2GBI) inhibits Hv1
      proton conduction by binding to the VSD from its intracellular side. Here, we
      examine the binding affinities of a series of 2GBI derivatives on human Hv1
      channels mutated at positions located in the core of the VSD and apply mutant
      cycle analysis to determine how the inhibitor interacts with the channel. We
      identify four Hv1 residues involved in the binding: aspartate 112, phenylalanine
      150, serine 181, and arginine 211. 2GBI appears to be oriented in the binding
      site with its benzo ring pointing to F150, its imidazole ring inserted between
      residue D112 and residues S181 and R211, and the guanidine group positioned in
      the proximity of R211. We also identify a modified version of 2GBI that is able
      to reach the binding site on Hv1 from the extracellular side of the membrane.
      Understanding how compounds like 2GBI interact with the Hv1 channel is an
      important step to the development of pharmacological treatments for diseases
      caused by Hv1 hyperactivity. 

PMID- 24912150
TI  - Encoding and storage of spatial information in the retrosplenial cortex.
AB  - The retrosplenial cortex (RSC) is part of a network of interconnected cortical,
      hippocampal, and thalamic structures harboring spatially modulated neurons. The
      RSC contains head direction cells and connects to the parahippocampal region and
      anterior thalamus. Manipulations of the RSC can affect spatial and contextual
      tasks. A considerable amount of evidence implicates the role of the RSC in
      spatial navigation, but it is unclear whether this structure actually encodes or
      stores spatial information. We used a transgenic mouse in which the expression of
      green fluorescent protein was under the control of the immediate early gene c-fos
      promoter as well as time-lapse two-photon in vivo imaging to monitor neuronal
      activation triggered by spatial learning in the Morris water maze. We uncovered a
      repetitive pattern of cell activation in the RSC consistent with the hypothesis
      that during spatial learning an experience-dependent memory trace is formed in
      this structure. In support of this hypothesis, we also report three other
      observations. First, temporary RSC inactivation disrupts performance in a spatial
      learning task. Second, we show that overexpressing the transcription factor CREB
      in the RSC with a viral vector, a manipulation known to enhance memory
      consolidation in other circuits, results in spatial memory enhancements. Third,
      silencing the viral CREB-expressing neurons with the allatostatin system occludes
      the spatial memory enhancement. Taken together, these results indicate that the
      retrosplenial cortex engages in the formation and storage of memory traces for
      spatial information. 

PMID- 24912151
TI  - Loss of the death receptor CD95 (Fas) expression by dendritic cells protects from
      a chronic viral infection.
AB  - Chronic viral infections incapacitate adaptive immune responses by "exhausting"
      virus-specific T cells, inducing their deletion and reducing productive T-cell
      memory. Viral infection rapidly induces death receptor CD95 (Fas) expression by
      dendritic cells (DCs), making them susceptible to elimination by the immune
      response. Lymphocytic choriomeningitis virus (LCMV) clone 13, which normally
      establishes a chronic infection, is rapidly cleared in C57Black6/J mice with
      conditional deletion of Fas in DCs. The immune response to LCMV is characterized
      by an extended survival of virus-specific effector T cells. Moreover, transfer of
      Fas-negative DCs from noninfected mice to preinfected animals results in either
      complete clearance of the virus or a significant reduction of viral titers. Thus,
      DC-specific Fas expression plays a role in regulation of antiviral responses and
      suggests a strategy for stimulation of T cells in chronically infected animals
      and humans to achieve the clearance of persistent viruses. 

PMID- 24912152
TI  - Pivotal role for the ubiquitin Y59-E51 loop in lysine 48 polyubiquitination.
AB  - Lysine 48 (K48)-polyubiquitination is the predominant mechanism for mediating
      selective protein degradation, but the underlying molecular basis of selecting
      ubiquitin (Ub) K48 for linkage-specific chain synthesis remains elusive. Here, we
      present biochemical, structural, and cell-based evidence demonstrating a pivotal
      role for the Ub Y59-E51 loop in supporting K48-polyubiquitination. This loop is
      established by a hydrogen bond between Ub Y59's hydroxyl group and the backbone
      amide of Ub E51, as substantiated by NMR spectroscopic analysis. Loop residues
      Y59 and R54 are specifically required for the receptor activity enabling K48 to
      attack the donor Ub-E2 thiol ester in reconstituted ubiquitination catalyzed by
      Skp1-Cullin1-F-box (SCF)(betaTrCP) E3 ligase and Cdc34 E2-conjugating enzyme.
      When introduced into mammalian cells, loop-disruptive mutant Ub(R54A/Y59A)
      diminished the production of K48-polyubiquitin chains. Importantly, conditional
      replacement of human endogenous Ub by Ub(R54A/Y59A) or Ub(K48R) yielded profound
      apoptosis at a similar extent, underscoring the global impact of the Ub Y59-E51
      loop in cellular K48-polyubiquitination. Finally, disulfide cross-linking
      revealed interactions between the donor Ub-bound Cdc34 acidic loop and the Ub K48
      site, as well as residues within the Y59-E51 loop, suggesting a mechanism in
      which the Ub Y59-E51 loop helps recruit the E2 acidic loop that aligns the
      receptor Ub K48 to the donor Ub for catalysis. 

PMID- 24912153
TI  - Synthesis of terephthalic acid via Diels-Alder reactions with ethylene and
      oxidized variants of 5-hydroxymethylfurfural.
AB  - Terephthalic acid (PTA), a monomer in the synthesis of polyethylene terephthalate
      (PET), is obtained by the oxidation of petroleum-derived p-xylene. There is
      significant interest in the synthesis of renewable, biomass-derived PTA. Here,
      routes to PTA starting from oxidized products of 5-hydroxymethylfurfural (HMF)
      that can be produced from biomass are reported. These routes involve Diels-Alder
      reactions with ethylene and avoid the hydrogenation of HMF to 2,5-dimethylfuran.
      Oxidized derivatives of HMF are reacted with ethylene over solid Lewis acid
      catalysts that do not contain strong Bronsted acids to synthesize intermediates
      of PTA and its equally important diester, dimethyl terephthalate (DMT). The
      partially oxidized HMF, 5-(hydroxymethyl)furoic acid (HMFA), is reacted with high
      pressure ethylene over a pure-silica molecular sieve containing framework tin (Sn
      Beta) to produce the Diels-Alder dehydration product, 4-(hydroxymethyl)benzoic
      acid (HMBA), with 31% selectivity at 61% HMFA conversion after 6 h at 190 
      degrees C. If HMFA is protected with methanol to form methyl 5
      (methoxymethyl)furan-2-carboxylate (MMFC), MMFC can react with ethylene in the
      presence of Sn-Beta for 2 h to produce methyl 4-(methoxymethyl)benzenecarboxylate
      (MMBC) with 46% selectivity at 28% MMFC conversion or in the presence of a pure
      silica molecular sieve containing framework zirconium (Zr-Beta) for 6 h to
      produce MMBC with 81% selectivity at 26% MMFC conversion. HMBA and MMBC can then
      be oxidized to produce PTA and DMT, respectively. When Lewis acid containing
      mesoporous silica (MCM-41) and amorphous silica, or Bronsted acid containing
      zeolites (Al-Beta), are used as catalysts, a significant decrease in
      selectivity/yield of the Diels-Alder dehydration product is observed. 

PMID- 24912154
TI  - From confluent human iPS cells to self-forming neural retina and retinal
      pigmented epithelium.
AB  - Progress in retinal-cell therapy derived from human pluripotent stem cells
      currently faces technical challenges that require the development of easy and
      standardized protocols. Here, we developed a simple retinal differentiation
      method, based on confluent human induced pluripotent stem cells (hiPSC),
      bypassing embryoid body formation and the use of exogenous molecules, coating, or
      Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self
      forming neural retina (NR)-like structures containing retinal progenitor cells
      (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal
      cell types in maturated NR-like structures as floating cultures, thereby
      revealing the multipotency of RPCs generated from integration-free hiPSCs.
      Furthermore, Notch pathway inhibition boosted the generation of photoreceptor
      precursor cells, crucial in establishing cell therapy strategies. This innovative
      process proposed here provides a readily efficient and scalable approach to
      produce retinal cells for regenerative medicine and for drug-screening purposes,
      as well as an in vitro model of human retinal development and disease. 

PMID- 24912156
TI  - Geomechanical behavior of the reservoir and caprock system at the In Salah CO2
      storage project.
AB  - Almost 4 million metric tons of CO2 were injected at the In Salah CO2 storage
      site between 2004 and 2011. Storage integrity at the site is provided by a 950-m
      thick caprock that sits above the injection interval. This caprock consists of a
      number of low-permeability units that work together to limit vertical fluid
      migration. These are grouped into main caprock units, providing the primary seal,
      and lower caprock units, providing an additional buffer and some secondary
      storage capacity. Monitoring observations at the site indirectly suggest that
      pressure, and probably CO2, have migrated upward into the lower portion of the
      caprock. Although there are no indications that the overall storage integrity has
      been compromised, these observations raise interesting questions about the
      geomechanical behavior of the system. Several hypotheses have been put forward to
      explain the measured pressure, seismic, and surface deformation behavior. These
      include fault leakage, flow through preexisting fractures, and the possibility
      that injection pressures induced hydraulic fractures. This work evaluates these
      hypotheses in light of the available data. We suggest that the simplest and most
      likely explanation for the observations is that a portion of the lower caprock
      was hydrofractured, although interaction with preexisting fractures may have
      played a significant role. There are no indications, however, that the overall
      storage complex has been compromised, and several independent data sets
      demonstrate that CO2 is contained in the confinement zone. 

PMID- 24912155
TI  - GABAA receptor target of tetramethylenedisulfotetramine.
AB  - Use of the highly toxic and easily prepared rodenticide
      tetramethylenedisulfotetramine (TETS) was banned after thousands of accidental or
      intentional human poisonings, but it is of continued concern as a chemical threat
      agent. TETS is a noncompetitive blocker of the GABA type A receptor (GABAAR), but
      its molecular interaction has not been directly established for lack of a
      suitable radioligand to localize the binding site. We synthesized [(14)C]TETS (14
      mCi/mmol, radiochemical purity >99%) by reacting sulfamide with H(14)CHO and s
      trioxane then completion of the sequential cyclization with excess HCHO. The
      outstanding radiocarbon sensitivity of accelerator mass spectrometry (AMS)
      allowed the use of [(14)C]TETS in neuroreceptor binding studies with rat brain
      membranes in comparison with the standard GABAAR radioligand 4'-ethynyl-4-n
      [(3)H]propylbicycloorthobenzoate ([(3)H]EBOB) (46 Ci/mmol), illustrating the use
      of AMS for characterizing the binding sites of high-affinity (14)C radioligands.
      Fourteen noncompetitive antagonists of widely diverse chemotypes assayed at 1 or
      10 uM inhibited [(14)C]TETS and [(3)H]EBOB binding to a similar extent (r(2) =
      0.71). Molecular dynamics simulations of these 14 toxicants in the pore region of
      the alpha1beta2gamma2 GABAAR predict unique and significant polar interactions
      for TETS with alpha1T1' and gamma2S2', which are not observed for EBOB or the
      GABAergic insecticides. Several GABAAR modulators similarly inhibited [(14)C]TETS
      and [(3)H]EBOB binding, including midazolam, flurazepam, avermectin Ba1,
      baclofen, isoguvacine, and propofol, at 1 or 10 MUM, providing an in vitro system
      for recognizing candidate antidotes. 

PMID- 24912157
TI  - Endogenous retrovirus induces leukemia in a xenograft mouse model for primary
      myelofibrosis.
AB  - The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous
      for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a
      wide-range of primary human cells, enabling sophisticated modeling of human
      disease. In studies designed to define neoplastic stem cells of primary
      myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound
      disruption of the hematopoietic microenvironment, we observed a high frequency of
      acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to
      PMF-xenografted mice, and contained multiple clonal integrations of ecotropic
      murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only
      observed in diseased mice, but also in nontreated NSG controls. Furthermore, in
      addition to the single ecotropic endogenous retrovirus (eERV) located on
      chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV
      integrations were observed in mice from each of four independent NSG mouse
      colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and
      that recombination events were not necessary for virus replication or AML
      induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine
      stimulation of mouse myeloid cells, which serve as targets for retroviral
      infection and transformation, as evidenced by integration into the Evi1 locus, a
      hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a
      role of paracrine stimulation in PMF disease progression, underlines the
      importance of target cell type and numbers in MuLV-induced disease, and mandates
      awareness of replicating MuLV in NOD immunodeficient mice, which can
      significantly influence experimental results and their interpretation. 

PMID- 24912158
TI  - Mechanisms underlying differential effectiveness of memantine and ketamine in
      rapid antidepressant responses.
AB  - Ketamine is an NMDA receptor (NMDAR) antagonist that elicits rapid antidepressant
      responses in patients with treatment-resistant depression. However, ketamine can
      also produce psychotomimetic effects that limit its utility as an antidepressant,
      raising the question of whether the clinically tolerated NMDAR antagonist
      memantine possesses antidepressant properties. Despite its similar potency to
      ketamine as an NMDAR antagonist, clinical data suggest that memantine does not
      exert rapid antidepressant actions for reasons that are poorly understood. In
      this study, we recapitulate the ketamine and memantine clinical findings in mice,
      showing that ketamine, but not memantine, has antidepressant-like effects in
      behavioral models. Using electrophysiology in cultured hippocampal neurons, we
      show that ketamine and memantine effectively block NMDAR-mediated miniature
      excitatory postsynaptic currents in the absence of Mg(2+). However, in
      physiological levels of extracellular Mg(2+), we identified key functional
      differences between ketamine and memantine in their ability to block NMDAR
      function at rest. This differential effect of ketamine and memantine extends to
      intracellular signaling coupled to NMDAR at rest, in that memantine does not
      inhibit the phosphorylation of eukaryotic elongation factor 2 or augment
      subsequent expression of BDNF, which are critical determinants of ketamine
      mediated antidepressant efficacy. These results demonstrate significant
      differences between the efficacies of ketamine and memantine on NMDAR-mediated
      neurotransmission that have impacts on downstream intracellular signaling, which
      we hypothesize is the trigger for rapid antidepressant responses. These data
      provide a novel framework on the necessary functional requirements of NMDAR
      mediated neurotransmission as a critical determinant necessary to elicit rapid
      antidepressant responses. 

PMID- 24912159
TI  - Chaos-order transition in foraging behavior of ants.
AB  - The study of the foraging behavior of group animals (especially ants) is of
      practical ecological importance, but it also contributes to the development of
      widely applicable optimization problem-solving techniques. Biologists have
      discovered that single ants exhibit low-dimensional deterministic-chaotic
      activities. However, the influences of the nest, ants' physical abilities, and
      ants' knowledge (or experience) on foraging behavior have received relatively
      little attention in studies of the collective behavior of ants. This paper
      provides new insights into basic mechanisms of effective foraging for social
      insects or group animals that have a home. We propose that the whole foraging
      process of ants is controlled by three successive strategies: hunting, homing,
      and path building. A mathematical model is developed to study this complex
      scheme. We show that the transition from chaotic to periodic regimes observed in
      our model results from an optimization scheme for group animals with a home.
      According to our investigation, the behavior of such insects is not represented
      by random but rather deterministic walks (as generated by deterministic dynamical
      systems, e.g., by maps) in a random environment: the animals use their
      intelligence and experience to guide them. The more knowledge an ant has, the
      higher its foraging efficiency is. When young insects join the collective to
      forage with old and middle-aged ants, it benefits the whole colony in the long
      run. The resulting strategy can even be optimal. 

PMID- 24912160
TI  - Visualizing synaptic vesicle turnover and pool refilling driven by calcium
      nanodomains at presynaptic active zones of ribbon synapses.
AB  - Ribbon synapses of photoreceptor cells and second-order bipolar neurons in the
      retina are specialized to transmit graded signals that encode light intensity.
      Neurotransmitter release at ribbon synapses exhibits two kinetically distinct
      components, which serve different sensory functions. The faster component is
      depleted within milliseconds and generates transient postsynaptic responses that
      emphasize changes in light intensity. Despite the importance of this fast release
      for processing temporal and spatial contrast in visual signals, the physiological
      basis for this component is not precisely known. By imaging synaptic vesicle
      turnover and Ca(2+) signals at single ribbons in zebrafish bipolar neurons, we
      determined the locus of fast release, the speed and site of Ca(2+) influx driving
      rapid release, and the location where new vesicles are recruited to replenish the
      fast pool after it is depleted. At ribbons, Ca(2+) near the membrane rose rapidly
      during depolarization to levels >10 uM, whereas Ca(2+) at nonribbon locations
      rose more slowly to the lower level observed globally, consistent with selective
      positioning of Ca(2+) channels near ribbons. The local Ca(2+) domain drove rapid
      exocytosis of ribbon-associated synaptic vesicles nearest the plasma membrane,
      accounting for the fast component of neurotransmitter release. However, new
      vesicles replacing those lost arrived selectively at the opposite pole of the
      ribbon, distal to the membrane. Overall, the results suggest a model for fast
      release in which nanodomain Ca(2+) triggers exocytosis of docked vesicles, which
      are then replaced by more distant ribbon-attached vesicles, creating
      opportunities for new vesicles to associate with the ribbon at membrane-distal
      sites. 

PMID- 24912161
TI  - Profile of Bruce Levin.

PMID- 24912162
TI  - IkappaB kinase-induced interaction of TPL-2 kinase with 14-3-3 is essential for
      Toll-like receptor activation of ERK-1 and -2 MAP kinases.
AB  - The MEK-1/2 kinase TPL-2 is critical for Toll-like receptor activation of the ERK
      1/2 MAP kinase pathway during inflammatory responses, but it can transform cells
      following C-terminal truncation. IkappaB kinase (IKK) complex phosphorylation of
      the TPL-2 C terminus regulates full-length TPL-2 activation of ERK-1/2 by a
      mechanism that has remained obscure. Here, we show that TPL-2 Ser-400
      phosphorylation by IKK and TPL-2 Ser-443 autophosphorylation cooperated to
      trigger TPL-2 association with 14-3-3. Recruitment of 14-3-3 to the
      phosphorylated C terminus stimulated TPL-2 MEK-1 kinase activity, which was
      essential for TPL-2 activation of ERK-1/2. The binding of 14-3-3 to TPL-2 was
      also indispensible for lipopolysaccharide-induced production of tumor necrosis
      factor by macrophages, which is regulated by TPL-2 independently of ERK-1/2
      activation. Our data identify a key step in the activation of TPL-2 signaling and
      provide a mechanistic insight into how C-terminal deletion triggers the oncogenic
      potential of TPL-2 by rendering its kinase activity independent of 14-3-3
      binding. 

PMID- 24912163
TI  - Characterization and development of photoactivatable fluorescent proteins for
      single-molecule-based superresolution imaging.
AB  - Photoactivatable fluorescent proteins (PAFPs) have been widely used for
      superresolution imaging based on the switching and localization of single
      molecules. Several properties of PAFPs strongly influence the quality of the
      superresolution images. These properties include (i) the number of photons
      emitted per switching cycle, which affects the localization precision of
      individual molecules; (ii) the ratio of the on- and off-switching rate constants,
      which limits the achievable localization density; (iii) the dimerization
      tendency, which could cause undesired aggregation of target proteins; and (iv)
      the signaling efficiency, which determines the fraction of target-PAFP fusion
      proteins that is detectable in a cell. Here, we evaluated these properties for 12
      commonly used PAFPs fused to both bacterial target proteins, H-NS, HU, and Tar,
      and mammalian target proteins, Zyxin and Vimentin. Notably, none of the existing
      PAFPs provided optimal performance in all four criteria, particularly in the
      signaling efficiency and dimerization tendency. The PAFPs with low dimerization
      tendencies exhibited low signaling efficiencies, whereas mMaple showed the
      highest signaling efficiency but also a high dimerization tendency. To address
      this limitation, we engineered two new PAFPs based on mMaple, which we termed
      mMaple2 and mMaple3. These proteins exhibited substantially reduced or
      undetectable dimerization tendencies compared with mMaple but maintained the high
      signaling efficiency of mMaple. In the meantime, these proteins provided photon
      numbers and on-off switching rate ratios that are comparable to the best achieved
      values among PAFPs. 

PMID- 24912165
TI  - Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade
      effector complexes.
AB  - Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR
      associated (Cas) systems protect bacteria and archaea from infection by viruses
      and plasmids. Central to this defense is a ribonucleoprotein complex that
      produces RNA-guided cleavage of foreign nucleic acids. In DNA-targeting CRISPR
      Cas systems, the RNA component of the complex encodes target recognition by
      forming a site-specific hybrid (R-loop) with its complement (protospacer) on an
      invading DNA while displacing the noncomplementary strand. Subsequently, the R
      loop structure triggers DNA degradation. Although these reactions have been
      reconstituted, the exact mechanism of R-loop formation has not been fully
      resolved. Here, we use single-molecule DNA supercoiling to directly observe and
      quantify the dynamics of torque-dependent R-loop formation and dissociation for
      both Cascade- and Cas9-based CRISPR-Cas systems. We find that the protospacer
      adjacent motif (PAM) affects primarily the R-loop association rates, whereas
      protospacer elements distal to the PAM affect primarily R-loop stability.
      Furthermore, Cascade has higher torque stability than Cas9 by using a
      conformational locking step. Our data provide direct evidence for directional R
      loop formation, starting from PAM recognition and expanding toward the distal
      protospacer end. Moreover, we introduce DNA supercoiling as a quantitative tool
      to explore the sequence requirements and promiscuities of orthogonal CRISPR-Cas
      systems in rapidly emerging gene-targeting applications. 

PMID- 24912166
TI  - Membrane raft association is a determinant of plasma membrane localization.
AB  - The lipid raft hypothesis proposes lateral domains driven by preferential
      interactions between sterols, sphingolipids, and specific proteins as a central
      mechanism for the regulation of membrane structure and function; however,
      experimental limitations in defining raft composition and properties have
      prevented unequivocal demonstration of their functional relevance. Here, we
      establish a quantitative, functional relationship between raft association and
      subcellular protein sorting. By systematic mutation of the transmembrane and
      juxtamembrane domains of a model transmembrane protein, linker for activation of
      T-cells (LAT), we generated a panel of variants possessing a range of raft
      affinities. These mutations revealed palmitoylation, transmembrane domain length,
      and transmembrane sequence to be critical determinants of membrane raft
      association. Moreover, plasma membrane (PM) localization was strictly dependent
      on raft partitioning across the entire panel of unrelated mutants, suggesting
      that raft association is necessary and sufficient for PM sorting of LAT.
      Abrogation of raft partitioning led to mistargeting to late endosomes/lysosomes
      because of a failure to recycle from early endosomes. These findings identify
      structural determinants of raft association and validate lipid-driven domain
      formation as a mechanism for endosomal protein sorting. 

PMID- 24912164
TI  - Impact of puberty on the evolution of cerebral perfusion during adolescence.
AB  - Puberty is the defining biological process of adolescent development, yet its
      effects on fundamental properties of brain physiology such as cerebral blood flow
      (CBF) have never been investigated. Capitalizing on a sample of 922 youths ages 8
      22 y imaged using arterial spin labeled MRI as part of the Philadelphia
      Neurodevelopmental Cohort, we studied normative developmental differences in
      cerebral perfusion in males and females, as well as specific associations between
      puberty and CBF. Males and females had conspicuously divergent nonlinear
      trajectories in CBF evolution with development as modeled by penalized splines.
      Seventeen brain regions, including hubs of the executive and default mode
      networks, showed a robust nonlinear age-by-sex interaction that surpassed
      Bonferroni correction. Notably, within these regions the decline in CBF was
      similar between males and females in early puberty and only diverged in
      midpuberty, with CBF actually increasing in females. Taken together, these
      results delineate sex-specific growth curves for CBF during youth and for the
      first time to our knowledge link such differential patterns of development to the
      effects of puberty. 

PMID- 24912167
TI  - Accounting for a mirror-image conformation as a subtle effect in protein folding.
AB  - By using local (free-energy profiles along the amino acid sequence and
      (13)C(alpha) chemical shifts) and global (principal component) analyses to
      examine the molecular dynamics of protein-folding trajectories, generated with
      the coarse-grained united-residue force field, for the B domain of staphylococcal
      protein A, we are able to (i) provide the main reason for formation of the mirror
      image conformation of this protein, namely, a slow formation of the second loop
      and part of the third helix (Asp29-Asn35), caused by the presence of multiple
      local conformational states in this portion of the protein; (ii) show that
      formation of the mirror-image topology is a subtle effect resulting from local
      interactions; (iii) provide a mechanism for how protein A overcomes the barrier
      between the metastable mirror-image state and the native state; and (iv) offer a
      plausible reason to explain why protein A does not remain in the metastable
      mirror-image state even though the mirror-image and native conformations are at
      least energetically compatible. 

PMID- 24912168
TI  - Commonness and rarity in the marine biosphere.
AB  - Explaining patterns of commonness and rarity is fundamental for understanding and
      managing biodiversity. Consequently, a key test of biodiversity theory has been
      how well ecological models reproduce empirical distributions of species
      abundances. However, ecological models with very different assumptions can
      predict similar species abundance distributions, whereas models with similar
      assumptions may generate very different predictions. This complicates inferring
      processes driving community structure from model fits to data. Here, we use an
      approximation that captures common features of "neutral" biodiversity models-
      which assume ecological equivalence of species--to test whether neutrality is
      consistent with patterns of commonness and rarity in the marine biosphere. We do
      this by analyzing 1,185 species abundance distributions from 14 marine ecosystems
      ranging from intertidal habitats to abyssal depths, and from the tropics to polar
      regions. Neutrality performs substantially worse than a classical nonneutral
      alternative: empirical data consistently show greater heterogeneity of species
      abundances than expected under neutrality. Poor performance of neutral theory is
      driven by its consistent inability to capture the dominance of the communities'
      most-abundant species. Previous tests showing poor performance of a neutral model
      for a particular system often have been followed by controversy about whether an
      alternative formulation of neutral theory could explain the data after all.
      However, our approach focuses on common features of neutral models, revealing
      discrepancies with a broad range of empirical abundance distributions. These
      findings highlight the need for biodiversity theory in which ecological
      differences among species, such as niche differences and demographic trade-offs,
      play a central role.

PMID- 24912169
TI  - Occurrence and core-envelope structure of 1-4* Earth-size planets around Sun-like
      stars.
AB  - Small planets, 1-4* the size of Earth, are extremely common around Sun-like
      stars, and surprisingly so, as they are missing in our solar system. Recent
      detections have yielded enough information about this class of exoplanets to
      begin characterizing their occurrence rates, orbits, masses, densities, and
      internal structures. The Kepler mission finds the smallest planets to be most
      common, as 26% of Sun-like stars have small, 1-2 R? planets with orbital periods
      under 100 d, and 11% have 1-2 R? planets that receive 1-4* the incident stellar
      flux that warms our Earth. These Earth-size planets are sprinkled uniformly with
      orbital distance (logarithmically) out to 0.4 the Earth-Sun distance, and
      probably beyond. Mass measurements for 33 transiting planets of 1-4 R? show that
      the smallest of them, R < 1.5 R?, have the density expected for rocky planets.
      Their densities increase with increasing radius, likely caused by gravitational
      compression. Including solar system planets yields a relation: rho = 2:32 + 3:19
      R=R ? [g cm(-3)]. Larger planets, in the radius range 1.5-4.0 R?, have densities
      that decline with increasing radius, revealing increasing amounts of low-density
      material (H and He or ices) in an envelope surrounding a rocky core, befitting
      the appellation ''mini-Neptunes.'' The gas giant planets occur preferentially
      around stars that are rich in heavy elements, while rocky planets occur around
      stars having a range of heavy element abundances. Defining habitable zones
      remains difficult, without benefit of either detections of life elsewhere or an
      understanding of life's biochemical origins.

PMID- 24912171
TI  - Structural and functional characterization of a conserved pair of bacterial
      cellulose-oxidizing lytic polysaccharide monooxygenases.
AB  - For decades, the enzymatic conversion of cellulose was thought to rely on the
      synergistic action of hydrolytic enzymes, but recent work has shown that lytic
      polysaccharide monooxygenases (LPMOs) are important contributors to this process.
      We describe the structural and functional characterization of two functionally
      coupled cellulose-active LPMOs belonging to auxiliary activity family 10 (AA10)
      that commonly occur in cellulolytic bacteria. One of these LPMOs cleaves
      glycosidic bonds by oxidation of the C1 carbon, whereas the other can oxidize
      both C1 and C4. We thus demonstrate that C4 oxidation is not confined to fungal
      AA9-type LPMOs. X-ray crystallographic structures were obtained for the enzyme
      pair from Streptomyces coelicolor, solved at 1.3 A (ScLPMO10B) and 1.5 A (CelS2
      or ScLPMO10C) resolution. Structural comparisons revealed differences in active
      site architecture that could relate to the ability to oxidize C4 (and that also
      seem to apply to AA9-type LPMOs). Despite variation in active site architecture,
      the two enzymes exhibited similar affinities for Cu(2+) (12-31 nM), redox
      potentials (242 and 251 mV), and electron paramagnetic resonance spectra, with
      only the latter clearly different from those of chitin-active AA10-type LPMOs. We
      conclude that substrate specificity depends not on copper site architecture, but
      rather on variation in substrate binding and orientation. During cellulose
      degradation, the members of this LPMO pair act in synergy, indicating different
      functional roles and providing a rationale for the abundance of these enzymes in
      biomass-degrading organisms. 

PMID- 24912170
TI  - Shear stress-dependent regulation of apical endocytosis in renal proximal tubule
      cells mediated by primary cilia.
AB  - The kidney has an extraordinary ability to maintain stable fractional solute and
      fluid reabsorption over a wide range of glomerular filtration rates (GFRs).
      Internalization of filtered low molecular weight proteins, vitamins, hormones,
      and other small molecules is mediated by the proximal tubule (PT) multiligand
      receptors megalin and cubilin. Changes in GFR and the accompanying fluid shear
      stress (FSS) modulate acute changes in PT ion transport thought to be mediated by
      microvillar bending. We found that FSS also affects apical endocytosis in PT
      cells. Exposure of immortalized PT cell lines to physiologically relevant levels
      of FSS led to dramatically increased internalization of the megalin-cubilin
      ligand albumin as well as the fluid phase marker dextran. FSS-stimulated apical
      endocytosis was initiated between 15 and 30 min postinduction of FSS, occurred
      via a clathrin- and dynamin-dependent pathway, and was rapidly reversed upon
      removing the FSS. Exposure to FSS also caused a rapid elevation in intracellular
      Ca(2+) [Ca(2+)]i, which was not observed in deciliated cells, upon treatment with
      BAPTA-AM, or upon inclusion of apyrase in the perfusion medium. Strikingly,
      deciliation, BAPTA-AM, and apyrase also blocked the flow-dependent increase in
      endocytosis. Moreover, addition of ATP bypassed the need for FSS in enhancing
      endocytic capacity. Our studies suggest that increased [Ca(2+)]i and purinergic
      signaling in response to FSS-dependent ciliary bending triggers a rapid and
      reversible increase in apical endocytosis that contributes to the efficient
      retrieval of filtered proteins in the PT. 

PMID- 24912172
TI  - Quantum critical behavior in heavy electron materials.
AB  - Quantum critical behavior in heavy electron materials is typically brought about
      by changes in pressure or magnetic field. In this paper, we develop a simple
      unified model for the combined influence of pressure and magnetic field on the
      effectiveness of the hybridization that plays a central role in the two-fluid
      description of heavy electron emergence. We show that it leads to quantum
      critical and delocalization lines that accord well with those measured for
      CeCoIn5, yields a quantitative explanation of the field and pressure-induced
      changes in antiferromagnetic ordering and quantum critical behavior measured for
      YbRh2Si2, and provides a valuable framework for describing the role of magnetic
      fields in bringing about quantum critical behavior in other heavy electron
      materials. 

PMID- 24912174
TI  - Navigability of interconnected networks under random failures.
AB  - Assessing the navigability of interconnected networks (transporting information,
      people, or goods) under eventual random failures is of utmost importance to
      design and protect critical infrastructures. Random walks are a good proxy to
      determine this navigability, specifically the coverage time of random walks,
      which is a measure of the dynamical functionality of the network. Here, we
      introduce the theoretical tools required to describe random walks in
      interconnected networks accounting for structure and dynamics inherent to real
      systems. We develop an analytical approach for the covering time of random walks
      in interconnected networks and compare it with extensive Monte Carlo simulations.
      Generally speaking, interconnected networks are more resilient to random failures
      than their individual layers per se, and we are able to quantify this effect. As
      an application--which we illustrate by considering the public transport of London
      -we show how the efficiency in exploring the multiplex critically depends on
      layers' topology, interconnection strengths, and walk strategy. Our findings are
      corroborated by data-driven simulations, where the empirical distribution of
      check-ins and checks-out is considered and passengers travel along fastest paths
      in a network affected by real disruptions. These findings are fundamental for
      further development of searching and navigability strategies in real
      interconnected systems. 

PMID- 24912173
TI  - Yolk-sac-derived macrophages regulate fetal testis vascularization and
      morphogenesis.
AB  - Organogenesis of the testis is initiated when expression of Sry in pre-Sertoli
      cells directs the gonad toward a male-specific fate. The cells in the early
      bipotential gonad undergo de novo organization to form testis cords that enclose
      germ cells inside tubules lined by epithelial Sertoli cells. Although Sertoli
      cells are a driving force in the de novo formation of testis cords, recent
      studies in mouse showed that reorganization of the vasculature and of
      interstitial cells also play critical roles in testis cord morphogenesis.
      However, the mechanism driving reorganization of the vasculature during fetal
      organogenesis remained unclear. Here we demonstrate that fetal macrophages are
      associated with nascent gonadal and mesonephric vasculature during the initial
      phases of testis morphogenesis. Macrophages mediate vascular reorganization and
      prune errant germ cells and somatic cells after testis architecture is
      established. We show that gonadal macrophages are derived from primitive yolk-sac
      hematopoietic progenitors and exhibit hallmarks of M2 activation status,
      suggestive of angiogenic and tissue remodeling functions. Depletion of
      macrophages resulted in impaired vascular reorganization and abnormal cord
      formation. These findings reveal a previously unappreciated role for macrophages
      in testis morphogenesis and suggest that macrophages are an intermediary between
      neovascularization and organ architecture during fetal organogenesis. 

PMID- 24912175
TI  - Hedgehog signaling mediates adaptive variation in a dynamic functional system in
      the cichlid feeding apparatus.
AB  - Adaptive variation in the craniofacial skeleton is a key component of resource
      specialization and habitat divergence in vertebrates, but the proximate genetic
      mechanisms that underlie complex patterns of craniofacial variation are largely
      unknown. Here we demonstrate that the Hedgehog (Hh) signaling pathway mediates
      widespread variation across a complex functional system that affects the
      kinematics of lower jaw depression--the opercular four-bar linkage apparatus-
      among Lake Malawi cichlids. By using a combined quantitative trait locus mapping
      and population genetics approach, we show that allelic variation in the Hh
      receptor, ptch1, affects the development of distinct bony elements in the head
      that represent two of three movable links in this functional system. The
      evolutionarily derived allele is found in species that feed from the water
      column, and is associated with shifts in anatomy that translate to a four-bar
      system capable of faster jaw rotation. Alternatively, the ancestral allele is
      found in species that feed on attached algae, and is associated with the
      development of a four-bar system that predicts slower jaw movement. Experimental
      manipulation of the Hh pathway during cichlid development recapitulates
      functionally salient natural variation in craniofacial geometry. In all, these
      results significantly extend our understanding of the mechanisms that fine-tune
      the craniofacial skeletal complex during adaptation to new foraging niches.

PMID- 24912176
TI  - Global evaluation of biofuel potential from microalgae.
AB  - In the current literature, the life cycle, technoeconomic, and resource
      assessments of microalgae-based biofuel production systems have relied on growth
      models extrapolated from laboratory-scale data, leading to a large uncertainty in
      results. This type of simplistic growth modeling overestimates productivity
      potential and fails to incorporate biological effects, geographical location, or
      cultivation architecture. This study uses a large-scale, validated, outdoor
      photobioreactor microalgae growth model based on 21 reactor- and species-specific
      inputs to model the growth of Nannochloropsis. This model accurately accounts for
      biological effects such as nutrient uptake, respiration, and temperature and uses
      hourly historical meteorological data to determine the current global
      productivity potential. Global maps of the current near-term microalgae lipid and
      biomass productivity were generated based on the results of annual simulations at
      4,388 global locations. Maximum annual average lipid yields between 24 and 27
      m(3).ha(-1).y(-1), corresponding to biomass yields of 13 to 15 g.m(-2).d(-1), are
      possible in Australia, Brazil, Colombia, Egypt, Ethiopia, India, Kenya, and Saudi
      Arabia. The microalgae lipid productivity results of this study were integrated
      with geography-specific fuel consumption and land availability data to perform a
      scalability assessment. Results highlight the promising potential of microalgae
      based biofuels compared with traditional terrestrial feedstocks. When water,
      nutrients, and CO2 are not limiting, many regions can potentially meet
      significant fractions of their transportation fuel requirements through
      microalgae production, without land resource restriction. Discussion focuses on
      sensitivity of monthly variability in lipid production compared with annual
      average yields, effects of temperature on productivity, and a comparison of
      results with previous published modeling assumptions. 

PMID- 24912177
TI  - Cognitive flexibility and long-term depression (LTD) are impaired following beta
      catenin stabilization in vivo.
AB  - The cadherin/beta-catenin adhesion complex is a key mediator of the bidirectional
      changes in synapse strength which are believed to underlie complex learning and
      memory. In the present study, we demonstrate that stabilization of beta-catenin
      in the hippocampus of adult mice results in significant impairments in cognitive
      flexibility and spatial reversal learning, including impaired extinction during
      the reversal phase of the Morris water maze and deficits in a delayed nonmatch to
      place T-maze task. In accordance with these deficits, beta-catenin stabilization
      was found to abolish long-term depression by stabilizing cadherin at the synaptic
      membrane and impairing AMPA receptor endocytosis, while leaving basal synaptic
      transmission and long-term potentiation unaffected. These results demonstrate
      that the beta-catenin/cadherin adhesion complex plays an important role in
      learning and memory and that aberrant increases in synaptic adhesion can have
      deleterious effects on cognitive function. 

PMID- 24912178
TI  - Dietary history contributes to enterotype-like clustering and functional
      metagenomic content in the intestinal microbiome of wild mice.
AB  - Understanding the origins of gut microbial community structure is critical for
      the identification and interpretation of potential fitness-related traits for the
      host. The presence of community clusters characterized by differences in the
      abundance of signature taxa, referred to as enterotypes, is a debated concept
      first reported in humans and later extended to other mammalian hosts. In this
      study, we provide a thorough assessment of their existence in wild house mice
      using a panel of evaluation criteria. We identify support for two clusters that
      are compositionally similar to clusters identified in humans, chimpanzees, and
      laboratory mice, characterized by differences in Bacteroides, Robinsoniella, and
      unclassified genera belonging to the family Lachnospiraceae. To further evaluate
      these clusters, we (i) monitored community changes associated with moving mice
      from the natural to a laboratory environment, (ii) performed functional
      metagenomic sequencing, and (iii) subjected wild-caught samples to stable isotope
      analysis to reconstruct dietary patterns. This process reveals differences in the
      proportions of genes involved in carbohydrate versus protein metabolism in the
      functional metagenome, as well as differences in plant- versus meat-derived food
      sources between clusters. In conjunction with wild-caught mice quickly changing
      their enterotype classification upon transfer to a standard laboratory chow diet,
      these results provide strong evidence that dietary history contributes to the
      presence of enterotype-like clustering in wild mice. 

PMID- 24912179
TI  - Switching brain serotonin with oxytocin.
AB  - Serotonin (5-HT) and oxytocin (OXT) are two neuromodulators involved in human
      affect and sociality and in disorders like depression and autism. We asked
      whether these chemical messengers interact in the regulation of emotion-based
      behavior by administering OXT or placebo to 24 healthy subjects and mapping
      cerebral 5-HT system by using 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro
      benzamidoethylpiperazine ([(18)F]MPPF), an antagonist of 5-HT1A receptors. OXT
      increased [(18)F]MPPF nondisplaceable binding potential (BPND) in the dorsal
      raphe nucleus (DRN), the core area of 5-HT synthesis, and in the
      amygdala/hippocampal complex, insula, and orbitofrontal cortex. Importantly, the
      amygdala appears central in the regulation of 5-HT by OXT: [(18)F]MPPF BPND
      changes in the DRN correlated with changes in right amygdala, which were in turn
      correlated with changes in hippocampus, insula, subgenual, and orbitofrontal
      cortex, a circuit implicated in the control of stress, mood, and social
      behaviors. OXT administration is known to inhibit amygdala activity and results
      in a decrease of anxiety, whereas high amygdala activity and 5-HT dysregulation
      have been associated with increased anxiety. The present study reveals a
      previously unidentified form of interaction between these two systems in the
      human brain, i.e., the role of OXT in the inhibitory regulation of 5-HT
      signaling, which could lead to novel therapeutic strategies for mental disorders.

PMID- 24912180
TI  - IL-15.IL-15Ralpha complex shedding following trans-presentation is essential for
      the survival of IL-15 responding NK and T cells.
AB  - Interleukin (IL)-15 and its specific receptor chain, IL-15Ralpha, support the
      development of various effector cells, including NK and CD8 T cells via a
      mechanism called trans-presentation. Whereas the dynamic of trans-presentation
      has been shown to involve the recycling of IL-15Ralpha by presenting cells, the
      way responding cells integrate, or take advantage of this process has not been
      evaluated yet. To address this question, we set up a trans-presentation model
      using a membrane-bound IL-15.IL-15Ralpha fusion protein, and found that IL-15 is
      detectable within responding cells following IL-15 trans-presentation. The role
      of the proteolytic cleavage of IL-15Ralpha in this process was investigated by
      generating an uncleavable form of IL-15Ralpha. We showed that IL-15 entry into
      responding cells necessitates the cleavage of IL-15.IL-15Ralpha complex from the
      surface of IL-15 presenting cells, and observed that IL-15Ralpha cleavage is
      associated with a decrease of the duration of Stat5 signaling. Once separated
      from presenting cells, responding cells are able to recycle IL-15.IL-15Ralpha
      complexes via intracellular compartments, for residual proliferation in a time
      limited manner. These studies define an unprecedented cytokine pathway in which
      the IL-15.IL-15Ralpha complex cleaved from presenting cells allows responding
      cells to internalize, store and use IL-15.IL-15Ralpha complex for their own
      proliferation and survival. 

PMID- 24912182
TI  - Scalable production of mechanically tunable block polymers from sugar.
AB  - Development of sustainable and biodegradable materials is essential for future
      growth of the chemical industry. For a renewable product to be commercially
      competitive, it must be economically viable on an industrial scale and possess
      properties akin or superior to existing petroleum-derived analogs. Few biobased
      polymers have met this formidable challenge. To address this challenge, we
      describe an efficient biobased route to the branched lactone, beta-methyl-delta
      valerolactone (betaMdeltaVL), which can be transformed into a rubbery (i.e., low
      glass transition temperature) polymer. We further demonstrate that block
      copolymerization of betaMdeltaVL and lactide leads to a new class of high
      performance polyesters with tunable mechanical properties. Key features of this
      work include the creation of a total biosynthetic route to produce betaMdeltaVL,
      an efficient semisynthetic approach that employs high-yielding chemical reactions
      to transform mevalonate to betaMdeltaVL, and the use of controlled polymerization
      techniques to produce well-defined PLA-PbetaMdeltaVL-PLA triblock polymers, where
      PLA stands for poly(lactide). This comprehensive strategy offers an economically
      viable approach to sustainable plastics and elastomers for a broad range of
      applications. 

PMID- 24912181
TI  - PipX, the coactivator of NtcA, is a global regulator in cyanobacteria.
AB  - To modulate the expression of genes involved in nitrogen assimilation, the
      cyanobacterial PII-interacting protein X (PipX) interacts with the global
      transcriptional regulator NtcA and the signal transduction protein PII, a protein
      found in all three domains of life as an integrator of signals of the nitrogen
      and carbon balance. PipX can form alternate complexes with NtcA and PII, and
      these interactions are stimulated and inhibited, respectively, by 2-oxoglutarate,
      providing a mechanistic link between PII signaling and NtcA-regulated gene
      expression. Here, we demonstrate that PipX is involved in a much wider
      interaction network. The effect of pipX alleles on transcript levels was studied
      by RNA sequencing of S. elongatus strains grown in the presence of either nitrate
      or ammonium, followed by multivariate analyses of relevant mutant/control
      comparisons. As a result of this process, 222 genes were classified into six
      coherent groups of differentially regulated genes, two of which, containing
      either NtcA-activated or NtcA-repressed genes, provided further insights into the
      function of NtcA-PipX complexes. The remaining four groups suggest the
      involvement of PipX in at least three NtcA-independent regulatory pathways. Our
      results pave the way to uncover new regulatory interactions and mechanisms in the
      control of gene expression in cyanobacteria. 

PMID- 24912183
TI  - Vaccinating captive chimpanzees to save wild chimpanzees.
AB  - Infectious disease has only recently been recognized as a major threat to the
      survival of Endangered chimpanzees and Critically Endangered gorillas in the
      wild. One potentially powerful tool, vaccination, has not been deployed in
      fighting this disease threat, in good part because of fears about vaccine safety.
      Here we report on what is, to our knowledge, the first trial in which captive
      chimpanzees were used to test a vaccine intended for use on wild apes rather than
      humans. We tested a virus-like particle vaccine against Ebola virus, a leading
      source of death in wild gorillas and chimpanzees. The vaccine was safe and
      immunogenic. Captive trials of other vaccines and of methods for vaccine delivery
      hold great potential as weapons in the fight against wild ape extinction. 

PMID- 24912184
TI  - Solid-state structures of peapod bearings composed of finite single-wall carbon
      nanotube and fullerene molecules.
AB  - A supramolecular combination of carbon nanotube and fullerene, so-called a
      peapod, has attracted much interest, not solely because of its physical
      properties but also for its unique assembled structures of carbonaceous entities.
      However, the detailed structural information available was not sufficient for in
      depth understanding of its structural chemistry or for exploratory research
      inspired by novel physical phenomena, mainly because of the severely
      inhomogeneous nature of currently available carbon nanotubes. We herein report
      solid-state structures of a molecular peapod. This structure, solved with a belt
      persistent finite carbon nanotube molecule at the atomic level by synchrotron X
      ray diffraction, revealed the presence of a smooth, inflection-free Hirshfeld
      surface inside the tube, and the smoothness permitted dynamic motion of the C60
      guest molecule even in the solid state. This precise structural information may
      inspire the molecular design of carbonaceous machines assembled purely through
      van der Waals contacts between two neutral molecules. 

PMID- 24912185
TI  - Investigation of triterpene synthesis and regulation in oats reveals a role for
      beta-amyrin in determining root epidermal cell patterning.
AB  - Sterols have important functions in membranes and signaling. Plant sterols are
      synthesized via the isoprenoid pathway by cyclization of 2,3-oxidosqualene to
      cycloartenol. Plants also convert 2,3-oxidosqualene to other sterol-like
      cyclization products, including the simple triterpene beta-amyrin. The function
      of beta-amyrin per se is unknown, but this molecule can serve as an intermediate
      in the synthesis of more complex triterpene glycosides associated with plant
      defense. beta-Amyrin is present at low levels in the roots of diploid oat (Avena
      strigosa). Oat roots also synthesize the beta-amyrin-derived triterpene glycoside
      avenacin A-1, which provides protection against soil-borne diseases. The genes
      for the early steps in avenacin A-1 synthesis [saponin-deficient 1 and 2 (Sad1
      and Sad2)] have been recruited from the sterol pathway by gene duplication and
      neofunctionalization. Here we show that Sad1 and Sad2 are regulated by an ancient
      root developmental process that is conserved across diverse species. Sad1
      promoter activity is dependent on an L1 box motif, implicating sterol/lipid
      binding class IV homeodomain leucine zipper transcription factors as potential
      regulators. The metabolism of beta-amyrin is blocked in sad2 mutants, which
      therefore accumulate abnormally high levels of this triterpene. The accumulation
      of elevated levels of beta-amyrin in these mutants triggers a "superhairy" root
      phenotype. Importantly, this effect is manifested very early in the establishment
      of the root epidermis, causing a greater proportion of epidermal cells to be
      specified as root hair cells rather than nonhair cells. Together these findings
      suggest that simple triterpenes may have widespread and as yet largely
      unrecognized functions in plant growth and development. 

PMID- 24912186
TI  - Up-regulation of glycolytic metabolism is required for HIF1alpha-driven bone
      formation.
AB  - The bone marrow environment is among the most hypoxic in the body, but how
      hypoxia affects bone formation is not known. Because low oxygen tension
      stabilizes hypoxia-inducible factor alpha (HIFalpha) proteins, we have
      investigated the effect of expressing a stabilized form of HIF1alpha in
      osteoblast precursors. Brief stabilization of HIF1alpha in SP7-positive cells in
      postnatal mice dramatically stimulated cancellous bone formation via marked
      expansion of the osteoblast population. Remarkably, concomitant deletion of
      vascular endothelial growth factor A (VEGFA) in the mouse did not diminish bone
      accrual caused by HIF1alpha stabilization. Thus, HIF1alpha-driven bone formation
      is independent of VEGFA up-regulation and increased angiogenesis. On the other
      hand, HIF1alpha stabilization stimulated glycolysis in bone through up-regulation
      of key glycolytic enzymes including pyruvate dehydrogenase kinase 1 (PDK1).
      Pharmacological inhibition of PDK1 completely reversed HIF1alpha-driven bone
      formation in vivo. Thus, HIF1alpha stimulates osteoblast formation through direct
      activation of glycolysis, and alterations in cellular metabolism may be a broadly
      applicable mechanism for regulating cell differentiation. 

PMID- 24912187
TI  - Nonequilibrium dynamics and ultraslow relaxation of confined DNA during viral
      packaging.
AB  - Many viruses use molecular motors that generate large forces to package DNA to
      near-crystalline densities inside preformed viral proheads. Besides being a key
      step in viral assembly, this process is of interest as a model for understanding
      the physics of charged polymers under tight 3D confinement. A large number of
      theoretical studies have modeled DNA packaging, and the nature of the molecular
      dynamics and the forces resisting the tight confinement is a subject of wide
      debate. Here, we directly measure the packaging of single DNA molecules in
      bacteriophage phi29 with optical tweezers. Using a new technique in which we
      stall the motor and restart it after increasing waiting periods, we show that the
      DNA undergoes nonequilibrium conformational dynamics during packaging. We show
      that the relaxation time of the confined DNA is >10 min, which is longer than the
      time to package the viral genome and 60,000 times longer than that of the
      unconfined DNA in solution. Thus, the confined DNA molecule becomes kinetically
      constrained on the timescale of packaging, exhibiting glassy dynamics, which
      slows the motor, causes significant heterogeneity in packaging rates of
      individual viruses, and explains the frequent pausing observed in DNA
      translocation. These results support several recent hypotheses proposed based on
      polymer dynamics simulations and show that packaging cannot be fully understood
      by quasistatic thermodynamic models. 

PMID- 24912188
TI  - Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic
      murine model of beryllium-induced disease.
AB  - Susceptibility to chronic beryllium disease (CBD) is linked to certain HLA-DP
      molecules, including HLA-DP2. To elucidate the molecular basis of this
      association, we exposed mice transgenic (Tg) for HLA-DP2 to beryllium oxide (BeO)
      via oropharyngeal aspiration. As opposed to WT mice, BeO-exposed HLA-DP2 Tg mice
      developed mononuclear infiltrates in a peribronchovascular distribution that were
      composed of CD4(+) T cells and included regulatory T (Treg) cells. Beryllium
      responsive, HLA-DP2-restricted CD4(+) T cells expressing IFN-gamma and IL-2 were
      present in BeO-exposed HLA-DP2 Tg mice and not in WT mice. Using Be-loaded HLA
      DP2-peptide tetramers, we identified Be-specific CD4(+) T cells in the mouse lung
      that recognize identical ligands as CD4(+) T cells derived from the human lung.
      Importantly, a subset of HLA-DP2 tetramer-binding CD4(+) T cells expressed
      forkhead box P3, consistent with the expansion of antigen-specific Treg cells.
      Depletion of Treg cells in BeO-exposed HLA-DP2 Tg mice exacerbated lung
      inflammation and enhanced granuloma formation. These findings document, for the
      first time to our knowledge, the development of a Be-specific adaptive immune
      response in mice expressing HLA-DP2 and the ability of Treg cells to modulate the
      beryllium-induced granulomatous immune response. 

PMID- 24912189
TI  - Control of catalytic efficiency by a coevolving network of catalytic and
      noncatalytic residues.
AB  - The active sites of enzymes consist of residues necessary for catalysis and
      structurally important noncatalytic residues that together maintain the
      architecture and function of the active site. Examples of evolutionary
      interactions between catalytic and noncatalytic residues have been difficult to
      define and experimentally validate due to a general intolerance of these residues
      to substitution. Here, using computational methods to predict coevolving
      residues, we identify a network of positions consisting of two catalytic metal
      binding residues and two adjacent noncatalytic residues in LAGLIDADG homing
      endonucleases (LHEs). Distinct combinations of the four residues in the network
      map to distinct LHE subfamilies, with a striking distribution of the metal
      binding Asp (D) and Glu (E) residues. Mutation of these four positions in three
      LHEs--I-LtrI, I-OnuI, and I-HjeMI--indicate that the combinations of residues
      tolerated are specific to each enzyme. Kinetic analyses under single-turnover
      conditions revealed that I-LtrI activity could be modulated over an ~100-fold
      range by mutation of residues in the coevolving network. I-LtrI catalytic site
      variants with low activity could be rescued by compensatory mutations at adjacent
      noncatalytic sites that restore an optimal coevolving network and vice versa. Our
      results demonstrate that LHE activity is constrained by an evolutionary barrier
      of residues with strong context-dependent effects. Creation of optimal coevolving
      active-site networks is therefore an important consideration in engineering of
      LHEs and other enzymes.

PMID- 24912191
TI  - Highly enantioselective synthesis of gamma-, delta-, and epsilon-chiral 1
      alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)-Cu- or Pd
      catalyzed cross-coupling.
AB  - Despite recent advances of asymmetric synthesis, the preparation of
      enantiomerically pure (>=99% ee) compounds remains a challenge in modern organic
      chemistry. We report here a strategy for a highly enantioselective (>=99% ee) and
      catalytic synthesis of various gamma- and more-remotely chiral alcohols from
      terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA
      reaction)-Cu- or Pd-catalyzed cross-coupling. ZACA-in situ oxidation of tert
      butyldimethylsilyl (TBS)-protected omega-alkene-1-ols produced both (R)- and (S)
      alpha,omega-dioxyfunctional intermediates (3) in 80-88% ee, which were readily
      purified to the >=99% ee level by lipase-catalyzed acetylation through
      exploitation of their high selectivity factors. These alpha,omega-dioxyfunctional
      intermediates serve as versatile synthons for the construction of various chiral
      compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl
      (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross
      coupling with aryl and alkenyl halides proceeded smoothly with essentially
      complete retention of stereochemical configuration to produce a wide variety of
      gamma-, delta-, and epsilon-chiral 1-alkanols of >=99% ee. The MalphaNP ester
      analysis has been applied to the determination of the enantiomeric purities of
      delta- and epsilon-chiral primary alkanols, which sheds light on the relatively
      undeveloped area of determination of enantiomeric purity and/or absolute
      configuration of remotely chiral primary alcohols. 

PMID- 24912190
TI  - Genome-wide RNAi screen identifies the Parkinson disease GWAS risk locus SREBF1
      as a regulator of mitophagy.
AB  - Genetic analysis of Parkinson disease (PD) has identified several genes whose
      mutation causes inherited parkinsonism, as well as risk loci for sporadic PD.
      PTEN-induced kinase 1 (PINK1) and parkin, linked to autosomal recessive PD, act
      in a common genetic pathway regulating the autophagic degradation of
      mitochondria, termed mitophagy. We undertook a genome-wide RNAi screen as an
      unbiased approach to identify genes regulating the PINK1/Parkin pathway. We
      identified several genes that have a conserved function in promoting
      mitochondrial translocation of Parkin and subsequent mitophagy, most notably
      sterol regulatory element binding transcription factor 1 (SREBF1), F-box and WD40
      domain protein 7 (FBXW7), and other components of the lipogenesis pathway. The
      relevance of mechanisms of autosomal recessive parkinsonism to sporadic PD has
      long been debated. However, with the recent identification of SREBF1 as a risk
      locus for sporadic PD, our findings suggest a common mechanistic link between
      autosomal recessive and sporadic PD, and underscore the importance of
      mitochondrial homeostasis. 

PMID- 24912192
TI  - PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors.
AB  - The molecular mechanisms underlying the development of pancreatic neuroendocrine
      tumors (PanNETs) have not been well defined. We report here that the genomic
      region of the PHLDA3 gene undergoes loss of heterozygosity (LOH) at a remarkably
      high frequency in human PanNETs, and this genetic change is correlated with
      disease progression and poor prognosis. We also show that the PHLDA3 locus
      undergoes methylation in addition to LOH, suggesting that a two-hit inactivation
      of the PHLDA3 gene is required for PanNET development. We demonstrate that PHLDA3
      represses Akt activity and Akt-regulated biological processes in pancreatic
      endocrine tissues, and that PHLDA3-deficient mice develop islet hyperplasia. In
      addition, we show that the tumor-suppressing pathway mediated by MEN1, a well
      known tumor suppressor of PanNETs, is dependent on the pathway mediated by
      PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET
      development. Collectively, these results indicate the existence of a novel PHLDA3
      mediated pathway of tumor suppression that is important in the development of
      PanNETs. 

PMID- 24912193
TI  - Reassessing the biogenicity of Earth's oldest trace fossil with implications for
      biosignatures in the search for early life.
AB  - Microtextures in metavolcanic pillow lavas from the Barberton greenstone belt of
      South Africa have been argued to represent Earth's oldest trace fossil,
      preserving evidence for microbial life in the Paleoarchean subseafloor. In this
      study we present new in situ U-Pb age, metamorphic, and morphological data on
      these titanite microtextures from fresh drill cores intercepting the type
      locality. A filamentous microtexture representing a candidate biosignature yields
      a U-Pb titanite age of 2.819 +/- 0.2 Ga. In the same drill core hornfelsic
      textured titanite discovered adjacent to a local mafic sill records an
      indistinguishable U-Pb age of 2.913 +/- 0.31 Ga, overlapping with the estimated
      age of intrusion. Quantitative microscale compositional mapping, combined with
      chlorite thermodynamic modeling, reveals that the titanite filaments are best
      developed in relatively low-temperature microdomains of the chlorite matrix. We
      find that the microtextures exhibit a morphological continuum that bears no
      similarity to candidate biotextures found in the modern oceanic crust. These new
      findings indicate that the titanite formed during late Archean ca. 2.9 Ga thermal
      contact metamorphism and not in an early ca. 3.45 Ga subseafloor environment. We
      therefore question the syngenicity and biogenicity of these purported trace
      fossils. It is argued herein that the titanite microtextures are more likely
      abiotic porphyroblasts of thermal contact metamorphic origin that record late
      stage retrograde cooling in the pillow lava country rock. A full characterization
      of low-temperature metamorphic events and alternative biosignatures in greenstone
      belt pillow lavas is thus required before candidate traces of life can be
      confirmed in Archean subseafloor environments. 

PMID- 24912194
TI  - Unitary step of gliding machinery in Mycoplasma mobile.
AB  - Among the bacteria that glide on substrate surfaces, Mycoplasma mobile is one of
      the fastest, exhibiting smooth movement with a speed of 2.0-4.5 MUm?s(-1) with a
      cycle of attachment to and detachment from sialylated oligosaccharides. To study
      the gliding mechanism at the molecular level, we applied an assay with a
      fluorescently labeled and membrane-permeabilized ghost model, and investigated
      the motility by high precision colocalization microscopy. Under conditions
      designed to reduce the number of motor interactions on a randomly oriented
      substrate, ghosts took unitary 70-nm steps in the direction of gliding. Although
      it remains possible that the stepping behavior is produced by multiple
      interactions, our data suggest that these steps are produced by a unitary gliding
      machine that need not move between sites arranged on a cytoskeletal lattice. 

PMID- 24912195
TI  - Mechanical constraints imposed by 3D cellular geometry and arrangement modulate
      growth patterns in the Arabidopsis embryo.
AB  - Morphogenesis occurs in 3D space over time and is guided by coordinated gene
      expression programs. Here we use postembryonic development in Arabidopsis plants
      to investigate the genetic control of growth. We demonstrate that gene expression
      driving the production of the growth-stimulating hormone gibberellic acid and
      downstream growth factors is first induced within the radicle tip of the embryo.
      The center of cell expansion is, however, spatially displaced from the center of
      gene expression. Because the rapidly growing cells have very different geometry
      from that of those at the tip, we hypothesized that mechanical factors may
      contribute to this growth displacement. To this end we developed 3D finite
      element method models of growing custom-designed digital embryos at cellular
      resolution. We used this framework to conceptualize how cell size, shape, and
      topology influence tissue growth and to explore the interplay of geometrical and
      genetic inputs into growth distribution. Our simulations showed that mechanical
      constraints are sufficient to explain the disconnect between the experimentally
      observed spatiotemporal patterns of gene expression and early postembryonic
      growth. The center of cell expansion is the position where genetic and mechanical
      facilitators of growth converge. We have thus uncovered a mechanism whereby 3D
      cellular geometry helps direct where genetically specified growth takes place. 

PMID- 24912197
TI  - Acute postexercise effects of concentric and eccentric exercise on glucose
      tolerance.
AB  - Impaired glucose tolerance was shown to be present 48 hr following muscle
      damaging eccentric exercise. We examined the acute effect of concentric and
      muscle-damaging eccentric exercise, matched for intensity, on the responses to a
      2-hr 75-g oral glucose tolerance test (OGTT). Ten men (27 +/- 9 years, 178 +/- 7
      cm, 75 +/- 11 kg, VO2max: 52.3 +/- 7.3 ml . kg-1 . min-1) underwent three OGTTs
      after an overnight 12 hr fast: rest (control), 40-min (5 * 8-min with 2-min
      interbout rest) of concentric (level running, 0%, CON) or eccentric exercise
      (downhill running, -12%, ECC). Running intensity was matched at 60% of maximal
      metabolic equivalent. Maximal isometric force of m. quadriceps femoris of both
      legs was measured before and after the running protocols. Downhill running speed
      was higher (level: 9.7 +/- 2.1, downhill: 13.8 +/- 3.2 km . hr-1, p < .01).
      Running protocols had similar VO2max (p = .59), heart rates (p = .20) and
      respiratory exchange ratio values (p = .74) indicating matched intensity and
      metabolic demands. Downhill running resulted in higher isometric force deficits
      (level: 3.0 +/- 6.7, downhill: 17.1 +/- 7.3%, p < .01). During OGTTs, area-under
      the-curve for plasma glucose (control: 724 +/- 97, CON: 710 +/- 77, ECC: 726 +/-
      72 mmol . L-1 . 120 min, p = .86) and insulin (control: 24995 +/- 11229, CON:
      23319 +/- 10417, ECC: 21842 +/- 10171 pmol . L-1 . 120 min, p = .48), peak
      glucose (control: 8.1 +/- 1.3, CON: 7.7 +/- 1.2, ECC: 7.7 +/- 1.1 mmol . L-1, p =
      .63) and peak insulin levels (control: 361 +/- 188, CON: 322 +/- 179, ECC: 299 +/
      152 pmol . L-1, p = .30) were similar. It was concluded that glucose tolerance
      and the insulin response to an OGTT were not changed immediately by muscle
      damaging eccentric exercise.

PMID- 24912196
TI  - Prosurvival Bcl-2 family members affect autophagy only indirectly, by inhibiting
      Bax and Bak.
AB  - Antiapoptotic B-cell lymphoma 2 (Bcl-2) family members such as Bcl-2, myeloid
      cell leukemia 1 (Mcl-1), and B-cell lymphoma-X large (Bcl-xL) are proposed to
      inhibit autophagy by directly binding to the BH3 domain of Beclin 1/Atg6.
      However, these Bcl-2 family proteins also block the proapoptotic activity of Bcl
      2-associated X (Bax) and Bcl-2 homologous antagonist/killer (Bak), and many
      inducers of autophagy also cause cell death. Therefore, when the mitochondrial
      mediated apoptosis pathway is functional, interpretation of such experiments is
      complicated. To directly test the impact of the endogenous antiapoptotic Bcl-2
      family members on autophagy in the absence of apoptosis, we inhibited their
      activity in cells lacking the essential cell death mediators Bax and Bak. We also
      used inducible lentiviral vectors to overexpress Bcl-2, Bcl-xL, or Mcl-1 in cells
      and subjected them to treatments that promote autophagy. In the absence of Bax
      and Bak, Bcl-2, Bcl-xL, and Mcl-1 had no detectable effect on autophagy or cell
      death in myeloid or fibroblast cell lines. On the other hand, when Bax and Bak
      were present, inhibiting the prosurvival Bcl-2 family members stimulated
      autophagy, but this correlated with increased cell death. In addition, inhibition
      of autophagy induced by amino acid starvation, etoposide, or interleukin-3
      withdrawal did not affect cell death in the absence of Bax and Bak. These results
      demonstrate that the antiapoptotic Bcl-2 family members do not directly inhibit
      components of the autophagic pathway but instead affect autophagy indirectly,
      owing to their inhibition of Bax and Bak. 

PMID- 24912198
TI  - Effect of knee and trunk angle on kinetic variables during the isometric midthigh
      pull: test-retest reliability.
AB  - The isometric midthigh pull (IMTP) has been used to monitor changes in force,
      maximum rate of force development (mRFD), and impulse, with performance in this
      task being associated with performance in athletic tasks. Numerous postures have
      been adopted in the literature, which may affect the kinetic variables during the
      task; therefore, the aim of this investigation was to determine whether different
      knee-joint angles (120 degrees , 130 degrees , 140 degrees , and 150 degrees )
      and hip-joint angles (125 degrees  and 145 degrees ), including the subjects
      preferred posture, affect force, mRFD, and impulse during the IMTP. Intraclass
      correlation coefficients demonstrated high within-session reliability (r >= .870,
      P < .001) for all kinetic variables determined in all postures, excluding impulse
      measures during the 130 degrees  knee-flexion, 125 degrees  hip-flexion posture,
      which showed a low to moderate reliability (r = .666-.739, P < .001), while
      between-sessions testing demonstrated high reliability (r > .819, P < .001) for
      all kinetic variables. There were no significant differences in peak force (P >
      .05, Cohen d = 0.037, power = .408), mRFD (P > .05, Cohen d = 0.037, power =
      .409), or impulse at 100 ms (P > .05, Cohen d = 0.056, power = .609), 200 ms (P >
      .05, Cohen d = 0.057, power = .624), or 300 ms (P > .05, Cohen d = 0.061, power =
      .656) across postures. Smallest detectable differences demonstrated that changes
      in performance of >1.3% in peak isometric force, >10.3% in mRFD, >5.3% in impulse
      at 100 ms, >4.4% in impulse at 200 ms, and >7.1% in impulse at 300 ms should be
      considered meaningful, irrespective of posture. 

PMID- 24912199
TI  - The activity profile of elite male amateur boxing.
AB  - An activity profile of competitive 3 * 3-min elite-level amateur boxing was
      created from video footage of 29 Olympic final and semifinal bouts in 39 male
      boxers (mean +/- SD) age 25.1 +/- 3.6 y, height 178.3 +/- 10.4 cm, and body mass
      69.7 +/- 16.5 kg. Boxing at this level requires the ability to maintain an
      activity rate of ~1.4 actions/s, consisting of ~20 punches, ~2.5 defensive
      movements, and ~47 vertical hip movements, all per minute, over 3 subsequent
      rounds lasting ~200 s each. Winners had higher total punches landed (P = .041)
      and a lower ratio of punches thrown to landed (P = .027) than losers in round 3.
      The hook rear-hand landed was also higher for winners than losers in round 2 (P =
      .038) and round 3 (P = .016), and defensive movements were used less by winners
      (P = .036). However, the results suggest that technical discrimination between
      winners and losers is difficult; bout outcome may be more dependent on which
      punch is "lucky" enough to be scored by the judges or who appears to be dominant
      on the day. This study gives both boxers and coaches a good idea of where
      subelite boxers need to aim if they want to become among the best amateur boxers
      in the world. 

PMID- 24912200
TI  - The efficacy of a self-paced VO2max test during motorized treadmill exercise.
AB  - PURPOSE: To assess the utility of a self-paced maximal oxygen uptake (VO2max)
      test (SPV) in eliciting an accurate measure of VO2max in comparison with a
      traditional graded exercise test (GXT) during motorized treadmill exercise.
      DESIGN: This was a cross-sectional experimental study whereby recreationally
      trained men (n = 13, 25.5 +/- 4.6 y) completed 2 maximal exercise tests (SPV,
      GXT) separated by a 72-h recovery period. METHODS: The GXT was continuous and
      incremental, with prescribed 1-km/h increases every 2 min until the attainment of
      VO2max. The SPV consisted of 5 * 2-min stages of incremental exercise, which were
      self-selected and adjusted according to 5 prescribed RPE levels (RPE 11, 13, 15,
      17, and 20). RESULTS: Although no significant differences in VO2max were observed
      between the SPV and GXT (63.9 +/- 3.3 cf 60.9 +/- 4.6 mL . kg-1 . min-1,
      respectively, P > .05), the apparent 4.7% mean difference may be practically
      important. The 95% limits-of-agreement analysis was 3.03 +/- 11.49 mL . kg-1 .
      min-1. Therefore, in the worst-case scenario, the GXT may underestimate measured
      VO2max as ascertained by the SPV by up to 19%. Conversely, the SPV could
      underestimate the GXT by 14%. CONCLUSIONS: The current study has shown that the
      SPV is an accurate measure of VO2max during exercise on a motorized treadmill and
      may provide a slightly higher VO2max value than that obtained from a traditional
      GXT. The higher VO2max during the SPV may be important when prescribing training
      or monitoring athlete progression.

PMID- 24912201
TI  - Alternative countermovement-jump analysis to quantify acute neuromuscular
      fatigue.
AB  - PURPOSE: To examine the reliability and magnitude of change after fatiguing
      exercise in the countermovement-jump (CMJ) test and determine its suitability for
      the assessment of fatigue-induced changes in neuromuscular (NM) function. A
      secondary aim was to examine the usefulness of a set of alternative CMJ variables
      (CMJ-ALT) related to CMJ mechanics. METHODS: Eleven male college-level team-sport
      athletes performed 6 CMJ trials on 6 occasions. A total of 22 variables, 16
      typical (CMJ-TYP) and 6 CMJ-ALT, were examined. CMJ reproducibility (coefficient
      of variation; CV) was examined on participants' first 3 visits. The next 3 visits
      (at 0, 24, and 72 h postexercise) followed a fatiguing high-intensity
      intermittent-exercise running protocol. Meaningful differences in CMJ performance
      were examined through effect sizes (ES) and comparisons to interday CV. RESULTS:
      Most CMJ variables exhibited intraday (n = 20) and interday (n = 21) CVs of <10%.
      ESs ranging from trivial to moderate were observed in 18 variables at 0 h
      (immediately postfatigue). Mean power, peak velocity, flight time, force at zero
      velocity, and area under the force-velocity trace showed changes greater than the
      CV in most individuals. At 24 h, most variables displayed trends toward a return
      to baseline. At 72 h, small increases were observed in time-related CMJ
      variables, with mean changes also greater than the CV. CONCLUSIONS: The CMJ test
      appears a suitable athlete-monitoring method for NM-fatigue detection. However,
      the current approach (ie, CMJ-TYP) may overlook a number of key fatigue-related
      changes, and so practitioners are advised to also adopt variables that reflect
      the NM strategy used.

PMID- 24912203
TI  - Diabetes tied to a third of California hospital stays, driving health care costs
      higher.
AB  - Increasing diabetes prevalence has been found to be a primary driver of increased
      health care costs in the United States. This policy brief examines the impact of
      diabetes on hospitalizations and related hospitalization costs in California.
      Using 2011 hospital patient discharge data and annual financial data from the
      Office of Statewide Health Planning and Development (OSHPD), this study found
      that patients with diabetes represented 31 percent of hospitalizations in
      California in 2011 among patients 35 years or older, including 39 percent of
      African-American and Asian-American patients and 43 percent of Latino patients.
      Moreover, these hospitalizations cost nearly $2,200 more per hospitalization than
      those for patients without diabetes, regardless of the primary reason for the
      hospitalization. Given that approximately 90-95 percent of diagnosed diabetes
      among adults is type 2 diabetes and is therefore preventable, public health
      measures can and should be taken to relieve the burden of type 2 diabetes. Such
      measures include promoting a healthy diet and regular physical activity and
      providing adequate access to primary and specialty care.

PMID- 24912204
TI  - Effects of inoculation of PAH-degrading bacteria and arbuscular mycorrhizal fungi
      on responses of ryegrass to phenanthrene and pyrene.
AB  - In order to investigate the effects of soil microorganisms on biochemical and
      physiological response of plants to PAHs, PAH-degrading bacteria (Acinetobacter
      sp.) and/or arbuscular mycorrhizal fungus (Glomus mosseae) were inoculated with
      ryegrass (Lolium multiflorum) under four different concentrations of phenanthrene
      and pyrene (0, 50 + 50, 100 + 100, 200 + 200 mg kg(-1)) in soils. Acinetobacter
      sp. played limited roles on the growth of ryegrass, chlorophyll content, water
      soluble carbohydrate content, malondialdehyde (MDA) content, activities of
      superoxide dismutase (SOD) and peroxidase (POD) in shoot. By contrast, G. mosseae
      significantly (P < 0.01) increased ryegrass growth, partially by improving the
      photosynthetic activity through increasing the chlorophyll content in shoot. G.
      mosseae also significantly decreased MDA content in shoot. However, G. mosseae
      significantly increased SOD activity in shoot, which seemed to be resulted from
      significantly higher pyrene concentrations in shoot. The present study suggested
      that AM fungi could reduce the damage of cell membranes caused by free radicals,
      which may be one of the mechanisms involved in mycorrhizal alleviation of plant
      stress under PAHs. The present study indicated that the dual inoculation was
      superior to single inoculation in remediating PAHs contaminated soils.

PMID- 24912205
TI  - Effects of adding nitroprusside on arsenic stressed response of Pistia stratiotes
      L. under hydroponic conditions.
AB  - Effect of nitric oxide (NO) in mitigating stress induced by arsenic (As) was
      assessed in Pistia stratiotes, with NO supplied as sodium nitroprusside (SNP).
      Plants were exposed to four treatments: control, SNP (0.1 mg L(-1)), As (1.5 mg
      L(-1)), As + SNP (1.5 and 0.1 mg L(-1)), for seven days (analyses of growth,
      absorption of As and mineral nutrients) and for 24 h (analyses of concentration
      of reactive oxygen intermediates (ROIs), antioxidant capacity and
      photosynthesis). P. stratiotes accumulated high concentrations of As and this
      accumulation wasn't affected by the addition of SNP, but the tolerance index of
      the plant to As increased. SNP attenuated effects of As on the absorption of
      mineral nutrients (Ca, Fe, Mn, and Mg), but not for phosphorus, and maintained
      concentrations of ROIs to normal levels, probably due to the increase in
      antioxidant capacity. The As damaged the photosynthesis by the decrease in
      pigment contents and by disturbance the photochemical (loss of PSII efficiency
      and increases in non-photochemical quenching coefficient) and biochemical
      (reductions in carbon assimilation, increase in the C(i)/C(a) and
      phi(PSII)/phi(CO2) ratios) steps. The addition of SNP restored these parameters
      to normal levels. Thus, NO was able to increasing the resistance of P. stratiotes
      to As.

PMID- 24912206
TI  - The effect of compost treatments and a plant cover with Agrostis tenuis on the
      immobilization/mobilization of trace elements in a mine-contaminated soil.
AB  - A semi-field experiment was conducted to evaluate the use of mixed municipal
      solid waste compost (MMSWC) and green waste-derived compost (GWC) as immobilizing
      agents in aided-phytostabilization of a highly acidic soil contaminated with
      trace elements, with and without a plant cover of Agrostis tenuis. The compost
      application ratio was 50 Mg ha(-1), and GWC amended soil was additionally limed
      and supplemented with mineral fertilizers. Both treatments had an equivalent
      capacity to raise soil organic matter and pH, without a significant increase in
      soil salinity and in pseudo-total As, Cu, Pb, and Zn concentrations, allowing the
      establishment of a plant cover. Effective bioavailable Cu and Zn decreased as a
      consequence of both compost treatments, while effective bioavailable As increased
      by more than twice but remained as a small fraction of its pseudo-total content.
      Amended soil had higher soil enzymatic activities, especially in the presence of
      plants. Accumulation factors for As, Cu, Pb, and Zn by A. tenuis were low, and
      their concentrations in the plant were lower than the maximum tolerable levels
      for cattle. As a consequence, the use of A. tenuis can be recommended for
      assisted phytostabilization of this type of mine soil, in combination with one of
      the compost treatments evaluated.

PMID- 24912208
TI  - Improvement of Cr phytoremediation by Pistia stratiotes in presence of nutrients.
AB  - The effects of different concentrations of P and N, added separately or combined,
      on the Cr(III) accumulation capacity of P. stratiotes were studied. Plants and
      pond water with the addition of contaminant(s) were placed in plastic aquaria. Cr
      concentration was 5 mg L(-1), while P and N concentrations were 5 mg L(-1) or 10
      mg L(-1). Nutrient addition significantly favoured Cr removal and enhanced Cr
      translocation to leaves. In Cr treatments a high detritus formation from loss of
      root biomass was observed probably due to its toxicity. Cr was mainly accumulated
      in the detrital fraction, whereas P and N were retained fundamentally in leaves.
      A toxic effect was observed in the Cr + P10 and Cr + N10 treatments. These
      results could be applied to enhance Cr removal efficiency of constructed wetlands
      using P. stratiotes, where nutrient enrichment could be attained by treating
      sewage together with the industrial effluents.

PMID- 24912207
TI  - Uptake and toxicity of arsenic, copper, and silicon in Azolla caroliniana and
      Lemna minor.
AB  - Here we report on the analysis of two aquatic plant species, Azolla caroliniana
      and Lemna minor, with respect to tolerance and uptake of co-occurring arsenic,
      copper, and silicon for use in engineered wetlands. Plants were cultured in
      nutrient solution that was amended with arsenic (0 or 20 microM), copper (2 or 78
      microM), and silicon (0 or 1.8 mM) either singly or in combination. We
      hypothesized that arsenic and copper would negatively affect the uptake of
      metals, growth, and pigmentation and that silicon would mitigate those stresses.
      Tolerance was assessed by measuring growth of biomass and concentrations of
      chlorophyll and anthocyanins. Both plant species accumulated arsenic, copper, and
      silicon; L. minor generally had higher levels on a per biomass basis. Arsenic
      negatively impacted A. caroliniana, causing a 30% decrease in biomass production
      and an increase in the concentration of anthocyanin. Copper negatively impacted
      L. minor, causing a 60% decrease in biomass production and a 45% decrease in
      chlorophyll content. Silicon augmented the impact of arsenic on biomass
      production in A. caroliniana but mitigated the effect of copper on L. minor. Our
      results suggest that mixtures of plant species may be needed to maximize uptake
      of multiple contaminants in engineered wetlands.

PMID- 24912209
TI  - Phytoremediation of heavy and transition metals aided by legume-rhizobia
      symbiosis.
AB  - Legumes are important for nitrogen cycling in the environment and agriculture due
      to the ability of nitrogen fixation by rhizobia. In this review, we introduce an
      important and potential role of legume-rhizobia symbiosis in aiding
      phytoremediation of some metal contaminated soils as various legumes have been
      found to be the dominant plant species in metal contaminated areas. Resistant
      rhizobia used for phytoremediation could act on metals directly by chelation,
      precipitation, transformation, biosorption and accumulation. Moreover, the plant
      growth promoting (PGP) traits of rhizobia including nitrogen fixation, phosphorus
      solubilization, phytohormone synthesis, siderophore release, and production of
      ACC deaminase and the volatile compounds of acetoin and 2, 3-butanediol may
      facilitate legume growth while lessening metal toxicity. The benefits of using
      legumes inoculated with naturally resistant rhizobia or recombinant rhizobia with
      enhanced resistance, as well as co-inoculation with other plant growth promoting
      bacteria (PGPB) are discussed. However, the legume-rhizobia symbiosis appears to
      be sensitive to metals, and the effect of metal toxicity on the interaction
      between legumes and rhizobia is not clear. Therefore, to obtain the maximum
      benefits from legumes assisted by rhizobia for phytoremediation of metals, it is
      critical to have a good understanding of interactions between PGP traits, the
      symbiotic plant-rhizobia relationship and metals.

PMID- 24912210
TI  - Effect of water velocity on hydroponic phytoremediation of metals.
AB  - The influence of flow velocity on the uptake of cadmium, copper, lead, and zinc
      by hydroponically grown soft stem bulrush (Scirpus validus) was investigated. The
      roots of the plants were exposed to a continually recycled, nutrient enriched,
      synthetic stormwater. Plants were divided into groups and the roots of each group
      exposed to different but constant water velocities. The metal concentrations in
      the roots and stems were compared after three weeks. Metal accumulation in roots
      was increased for water velocities between 1.3 and 4.0 cm s(-1). In a second
      experiment, the roots of all plants were exposed to a single velocity and the
      root and stem metal concentrations were determined as a function of time. Metal
      concentrations in the roots approached a constant value after three weeks. After
      this time, accumulation of metals depends upon root growth. The results suggest
      that long-term accumulation by the roots of hydroponic Scirpus validus can be
      increased by increasing water velocity, which implies that floating islands with
      movement will retain more metals from the water column.

PMID- 24912211
TI  - Phytotreatment of sewage sludge contaminated by heavy metals and PAHs by co
      planting Sedum alfredii and Alocasia marorrhiza.
AB  - High concentrations of heavy metals and organic pollutants in municipal sewage
      sludge are key factors limiting its use in agriculture. The objectives of this
      study were to decrease the heavy metal and polycyclic aromatic hydrocarbon
      concentrations in sewage sludge by phytotreatment and to determine, in a field
      experiment, whether co-planting is more effective than using a mono-crop of Sedum
      alfredii. Four treatments were used in the plot experiment: no sludge, no plants,
      S. alfredii and co-planting S. alfredii and Alocasia marorrhiza. The results
      showed that co-planting produced tubers and shoots of A. marorrhiza that were
      suitable as a safe animal feed and good organic K fertilizer, respectively. Co
      planting was more effective than mono-planting at reducing concentrations of
      total Zn and diethylenetriaminepentaacetic acid (DTPA)-extractable Zn, Cd, and Cu
      in the sludge. Co-planting decreased the concentrations of DTPA-extractable heavy
      metals and benzo[a]pyrene (B[a]P) in the sludge significantly compared with the
      unplanted sludge. Decreases of 87, 75, 85, 31, and 64% were obtained for B[a]P
      and DTPA-extractable Zn, Cd, Cu, and Pb, respectively, compared with the fresh
      sludge. These results indicate that co-planting can reduce significantly the
      environmental risks associated with heavy metals and B[a]P in sewage sludge for
      further disposal.

PMID- 24912212
TI  - Kocuria flava induced growth and chromium accumulation in Cicer arietinum L.
AB  - In the present investigation a chromate tolerant rhizobacterium Kocuria flava was
      isolated and inoculated to the Cicer arietinum L to evaluate its effects on
      growth and chromium accumulation upon exposure of different concentration of
      chromium (1-10 microg ml(-1)) as Cr (VI) for 24 d. K. flava inoculated plant of
      C. arietinum demonstrated luxuriant growth as compared to non inoculated plant at
      respective concentration of Cr (VI). K. flava found to ameliorate chromium
      induced phytotoxicity in terms of chlorophylls, carotenoid and protein contents
      and thus helps the plant in acquiring higher biomass with high chromium
      concentration. After 24 d, maximum concentration of chromium recorded in root of
      C. arietinum (4892.39 microg g(-1) dw) inoculated with K. flava as compared to
      non inoculated plant (1762.22 microg g(-1) dw) upon exposure of 5 microg ml(-1)
      Cr (VI). Therefore, application of C. arietinum in association with K. flava
      could be more efficient in decontamination of chromium polluted site. Moreover,
      K. flava may be used as a bioresource for developing microbes assisted
      phytoremediation system due to its compatibility.

PMID- 24912213
TI  - Bioaccumulation potential and physiological responses of aquatic macrophytes to
      Pb pollution.
AB  - In view of their potential bioaccumulation of heavy metals, Ceratophyllum
      demersum and Myriophyllum spicatum was studied under hydroponic cultures enriched
      by different Pb concentrations (25, 50, 75 mg/l) for 1-7 days. Both species
      exerted remarkable capabilities to concentrate Pb in their tissues as compared to
      control. The highest accumulation value of Pb (164.26 mg/g x dw) was recorded in
      C. demersum and the most of metal (91.72 mg/g dw) accumulated after 1 d.
      Significant reduction in photosynthetic pigments and appearance of morphological
      symptoms such as chlorosis and fragmentation of leaves were evident after 7d at
      75 mg/l. The activity of POX and APX, carotenoids and proline showed induction at
      lower concentration and duration followed by decline. Major re-shuffle in protein
      patterns appeared as a tolerant mechanism, which both species developed under Pb
      toxicity. Results suggest that both species responded positively to Pb
      concentration and accumulated high amount of metal. Due to metal accumulation
      coupled with detoxification potential, both species appear to have potential for
      use as phytoremediators and the developed responses can be used as reliable
      biomarkers for Pb water pollution.

PMID- 24912214
TI  - PAH phytoremediation: rhizodegradation or rhizoattenuation?
AB  - Dealing with soil contaminated with persistent organic pollutants (POP) is an
      increasing concern amplified by both regulatory constraints and the dramatic
      impact of human activities on the soil resource. The most used management options
      are treatments which totally eradicate the toxic compounds targeted. When
      possible, environmental-friendly processes should be used, and recent years have
      seen the emergence of green technologies using biological energies involving
      microorganisms (bioremediation) and plants (phytoremediation). Research has
      focused on phytoremediation and many have presented this technology as the
      process ideally combining efficiency, low cost and environmental acceptance.
      However, the applicability of phytoremediation on soils contaminated by bio
      recalcitrant organic compounds, such as polycyclic aromatic hydrocarbons (PAH),
      has not yet proved as successful as expected. We propose here a review and
      discussion of the overall question of PAH status in soil and their potential for
      treatment. The limits and applicability of bioremediation technologies are
      discussed, and the specific beneficial effect of plants is objectively evaluated
      with a special interest to processes which lead to rhizoattenuation. Given the
      PAH high affinity to soil organic matter, availability is the main limitation to
      phytoremediation. In this context, bioavailability quantification remains an
      issue as well as the characterization of the recalcitrant fraction.

PMID- 24912215
TI  - Disposition of atrazine metabolites following uptake and degradation of atrazine
      in switchgrass.
AB  - Extensive use of the agricultural herbicide atrazine has led to contamination of
      numerous ground and surface water bodies. Research has shown that it can have a
      variety of negative impacts on numerous non-target organisms in the environment.
      Phytoremediation is one strategy that has been studied to remove atrazine
      contamination. This paper investigates the hypothesis that switchgrass (Panicum
      virgatum) can exude metabolites of atrazine after uptake and degradation, which
      has been suggested by prior research. Pots planted with switchgrass were treated
      with a 4 ppm solution of atrazine spiked with [14C]atrazine. After 4 days,
      switchgrass plants were transplanted to new pots with fresh sand. Four days
      later, the pots were sacrificed, and sand and plant samples were extracted. Plant
      and sand samples were analyzed for the presence of atrazine and its major
      metabolites. The percentage of radiotracer remaining as the parent atrazine was
      observed to decrease over the course of the study while the percentages of the
      metabolites were observed to increase. The presence of the metabolite cyanuric
      acid in a switchgrass phytoremediation system is reported for the first time.

PMID- 24912216
TI  - Management of Atriplex nummularia Lindl. in a salt affected soil in a semi arid
      region of Brazil.
AB  - This study aims to investigate the behavior of Atriplex nummularia under field
      conditions, including its growth, periodic cuttings, salt extraction, and soil
      chemical properties monitored for 16 months. Three treatments were evaluated:
      soil cultivated with Atriplex pruned at 6 and 12 months after transplanting
      (MAT); soil cultivated with plants that were harvested only at the end of the
      experiment (16 MAT); and a control (uncultivated soil) with four replications.
      Soil samplings were taken at 0, 6, 12, and 16 MAT. The samples were taken at
      depths of 0-20, 20-40, 40-60, and 60-80 cm. Biometric variables for growth were
      monitored monthly. The shoot was divided into leaves, thin stems (< or = 3 mm
      diameter), and thick stems (> 3 mm diameter) to determine its content of Ca, Mg,
      Na, K, and Cl. We concluded that pruning regime for Atriplex was efficient mainly
      because it stimulated regrowth of less lignified material (leaves and stems < or
      = 3 mm). We found that elements extracted by plant tissue can be quantified
      accurately, making them valuable indicators of the efficiency of the recovery
      process. The use of the Atriplex is recommended because the the possibility of
      revegetating areas inhospitable to most species used in conventional farming.

PMID- 24912217
TI  - Effects of surface-modified nano-scale carbon black on Cu and Zn fractionations
      in contaminated soil.
AB  - Cu contamination soil (547 mg kg(-1)) was mixed separately with the surface
      modified nano-scale carbon black (MCB) and placed in the ratios (w/w) of 0, 1%,
      3%, and 5% in pots, together with 0.33 g KH2PO4 and 0.35 g urea/pot. Each pot
      contained 20 ryegrass seedlings (Lolium multiflorum). Greenhouse cultivation
      experiments were conducted to examine the effect of the MCB on Cu and Zn
      fractionations in soil, accumulation in shoot and growth of ryegrass. The results
      showed that the biomass of ryegrass shoot and root increased with the increasing
      of MCB adding amount (p < 0.05). The Cu and Zn accumulation in ryegrass shoot and
      the concentrations of DTPA extractable Cu and Zn in soil were significantly
      decreased with the increasing of MCB adding amount (p < 0.05). The metal contents
      of exchangeable and bound to carbonates (EC-Cu or EC-Zn) in the treatments with
      MCB were generally lower than those without MCB, and decreased with the
      increasing of MCB adding amount (p < 0.05). There was a positive linear
      correlation between the Cu and Zn accumulation in ryegrass shoot and the EC-Cu
      and EC-Zn in soil. The present results indicated the MCB could be applied for the
      remediation the soils polluted by Cu and Zn.

PMID- 24912218
TI  - Effectiveness of vetiver grass (Vetiveria zizanioides L. Nash) for
      phytoremediation of endosulfan in two cotton soils from Burkina Faso.
AB  - The influence of vetiver grass (Vetiveria zizanioides) on the fate of endosulfan
      was studied using a vertisol and a lixisol soils from cotton-growing areas of
      Burkina Faso. Endosulfan adsorption isotherms were prepared for planted and
      unplanted soils. Pot experiments were then conducted for six months. For both
      soils, endosulfan adsorption was higher on planted soils (K(f) = 6.53-9.73 mg(l
      n) L(n) kg(-1)) than on unplanted soils (6.27-7.24 mg(l-n) L(n) kg(-1)). In
      unplanted soils, vertisol adsorbed more endosulfan than lixisol. From the pot
      experiments, the estimated half-lives of endosulfan in unplanted soils (40.6 to
      43.1 days) were higher than in planted soils (34.5 to 40.6 days) containing a
      greater number of endosulfan-degrading microorganisms. Six months after
      treatment, endosulfan was not detected in soils. The effectiveness of vetiver in
      promoting adsorption and the disappearance of endosulfan in both studied soils
      should be validated on the cotton plot scale in Burkina Faso.

PMID- 24912219
TI  - Studies on phytoremediation of copper using Pteridium aquilinum (bracken fern) in
      the presence of biostimulants and bioassay using Clarias gariepinus juveniles.
AB  - A study was carried out to evaluate the uptake of copper from water containing 10
      mg/L copper by Pteridium aquilinum (bracken fern) and Clarias gariepinus in the
      presence of five plant growth stimulants: Nitrogen: phosphorus: potassium (15-15
      15: an inorganic fertilizer), pig, cattle, poultry, and a mixture of pig/cattle
      manures. A plant growth stimulant differentiated each treatment. A 96-hour
      bioassay using C. gariepinus was carried out at the end of the experiment to test
      the efficacy of the clean up by P. aquilinum. The control experiment contained no
      copper or plant growth stimulant. Fish survival, uptake of copper by P.
      aquilinum, C. gariepinus, concentration of copper in water, hematology and
      histopathology of the fish were assessed. Higher concentrations of copper were
      reported in P. aquilinum than in water or C. gariepinus. Low fish mortality was
      reported with the highest being 20% in the cattle manure-containing treatment.

PMID- 24912220
TI  - Neotyphodium coenophialum-infected tall fescue and its potential application in
      the phytoremediation of saline soils.
AB  - The growth response of endophyte-infected (EI) and endophyte-free (EF) tall
      fescue to salt stress was investigated under two growing systems (hydroponic and
      soil in pots). The hydroponic experiment showed that endophyte infection
      significantly increased tiller and leaf number, which led to an increase in the
      total biomass of the host grass. Endophyte infection enhanced Na accumulation in
      the host grass and improved Na transport from the roots to the shoots. With a 15
      g l(-1) NaCl treatment, the phytoextraction efficiency of EI tall fescue was 2.34
      fold higher than EF plants. When the plants were grown in saline soils, endophyte
      infection also significantly increased tiller number, shoot height and the total
      biomass of the host grass. Although EI tall fescue cannot accumulate Na to a
      level high enough for it to be termed a halophyte, the increased biomass
      production and stress tolerance suggested that endophyte/plant associations had
      the potential to be a model for endophyte-assisted phytoextraction in saline
      soils.

PMID- 24912221
TI  - Shielding property of natural biomass against gamma rays.
AB  - Algae and cyanobacteria are capable living under harsh conditions in the natural
      environments and can develop peculiar survival processes. In order to evaluate
      radiation shielding properties of green algae; Chlorella vulgaris, Scenedesmus
      obliquus, and cyanobacteria; Synechococcus sp., Planktothrix limnetica,
      Microcystis aeruginosa, Arthrospira maxima, Anabaena affinis, Phormidium
      articulatum, and Pseudoanabaena sp. were cultured in batch systems. Air dried
      biomass was tested for its high tolerance to gamma-radiations in terms of linear
      attenuation coefficients. In the present work, the linear and mass attenuation
      coefficients were measured at photon energies of 1173 and 1332 keV. Protection
      capacity of some biomass was observed to be higher than a 1-cm thick lead
      standard for comparison. Gamma ray related protection depends not only to
      thickness but also to density (g/cm3). Hence the effect of biomass density also
      was tested and significantly found the tested biomass absorbed more of the
      incoming energy on a density basis than lead. This paper discusses the a new
      approach to environmental protection from gamma ray. The findings suggest that
      the test samples, especially cyanobacteria, have a potential for reducing gamma
      ray more significantly than lead and can be used as shielding materials.

PMID- 24912222
TI  - Screening of As-accumulating plants using a foliar application and a native
      accumulation of As.
AB  - The discovery of novel accumulating plants is useful for efficient
      phytoremediation due to the demands of various conditions of impacted sites such
      as land use, soil properties, concentration of pollutants, and climate. In the
      present study, we investigated foliar application or a field with highly
      bioavailable arsenic (As) to screen As-accumulating plants. Plants grown in the
      downstream of a hot springs area were analyzed for native As accumulation and As
      foliar application, and the rhizosphere soils were collected. The water-soluble
      As in the rhizosphere soils had a high average, 144 microg/kg, whereas total As
      was similar to normal soil in Japan. Among 34 herbaceous plants and 17 woody
      plants, Chelidonium majus var. asiaticum accumulated a relatively high As level,
      8.07 mg/kg DW (93.6% of As added), that was not revealed by native accumulation.
      In a further pot experiment, C. majus accumulated a moderately high As level (314
      mg/kg DW) in the roots but not in the shoot (30.1 mg/kg DW), and exhibited a low
      transfer factor (TF = 0.096). Thus, a foliar application would be a simple and
      high-throughput method to screen plants that accumulate and tolerate As. C. majus
      would be useful as a tool for phytostabilization of As.

PMID- 24912223
TI  - A hydroponic system for growing gnotobiotic vs. sterile plants to study
      phytoremediation processes.
AB  - In some phytoremediation studies it is desirable to separate and define the
      specific contribution of plants and root-colonizing bacteria towards contaminant
      removal. Separating the influence of plants and associated bacteria is a
      difficult task for soil root environments. Growing plants hydroponically provides
      more control over the biological factors in contaminant removal. In this study, a
      hydroponic system was designed to evaluate the role of sterile plant roots,
      rhizodeposition, and root-associated bacteria in the removal of a model
      contaminant, phenol. A strain of Pseudomonas pseudoalcaligenes that grows on
      phenol was inoculated onto plant roots. The introduced biofilm persisted in the
      root zone and promoted phenol removal over non-augmented controls. These findings
      indicate that this hydroponic system can be a valuable tool for phytoremediation
      studies that investigate the effects of biotic and abiotic factors on pollution
      remediation.

PMID- 24912224
TI  - Phytoremediation potential of selected plants for nitrate and phosphorus from
      ground water.
AB  - The phytoremediation potential of three aquatic plants namely, water lettuce
      (Pistia stratioes), water hyacinth (Eichhornia crassipes), and water spinach
      (Ipomoea aquatica) for nitrate N and phosphorus from nutrient treated ground
      water was assessed. A total of twelve treatment combinations including four
      levels of nitrate (expressed as nitrate N 0, 20, 40, and 60 mg/l) and three
      levels of phosphorus (0, 20, and 40 mg/l) were treated for the total volume of 1
      and 20 liters of water respectively, for Pistia stratiotes and Eichhornia
      crassipes. For Ipomoea aquatica ten treatment combinations with five levels of
      nitrate N (0, 10, 20, 40, and 50 mg/l) and two levels of phosphorus (0 and 5
      mg/l) were treated to 3 liters of water. The design used was a two factor
      factorial with three replicates. Water was analyzed at weekly interval for
      nitrate N and phosphorus. Pistia stratiotes, Eichhornia crassipes and Ipomoea
      aquatica had the potential to remove nitrate N between 61.5-91.8%, 40-63.5%, and
      29.3-75% during the period of six, three and three and weeks, respectively. In
      addition, 90-99%, 75-97.2%, and 75-83.3% of phosphorus was removed from water by
      Pistia stratiotes, Eichhornia crassipes and Ipomoea aquatica respectively, during
      the same period.

PMID- 24912225
TI  - Controlled release fertilizer increased phytoremediation of petroleum
      contaminated sandy soil.
AB  - A greenhouse experiment was conducted to determine the effect of the application
      of controlled release fertilizer [(CRF) 0, 4,6, or 8 kg m(-3)] on Lolium
      multiflorum Lam. survival and potential biodegradation of petroleum hydrocarbons
      (0, 3000, 6000, or 15000 mg kg(-1)) in sandy soil. Plant adaptation, growth,
      photosynthesis, total chlorophyll, and proline content as well as rhizosphere
      microbial population (culturable heterotrophic fungal and bacterial populations)
      and total petroleum hydrocarbon (TPH)-degradation were determined. Petroleum
      induced-toxicity resulted in reduced plant growth, photosynthesis, and nutrient
      status. Plant adaptation, growth, photosynthesis, and chlorophyll content were
      enhanced by the application of CRF in contaminated soil. Proline content showed
      limited use as a physiological indicator of petroleum induced-stress in plants.
      Bacterial and filamentous fungi populations were stimulated by the petroleum
      concentrations. Bacterial populations were stimulated by CRF application. At low
      petroleum contamination, CRF did not enhance TPH-degradation. However, petroleum
      degradation in the rhizosphere was enhanced by the application of medium rates of
      CRF, especially when plants were exposed to intermediate and high petroleum
      contamination. Application of CRF allowed plants to overcome the growth
      impairment induced by the presence of petroleum hydrocarbons in soils.

PMID- 24912226
TI  - Phytoremediation potential of weeds in heavy metal contaminated soils of the
      Bassa Industrial Zone of Douala, Cameroon.
AB  - Phytoremediation is a promising option for reclaiming soils contaminated with
      toxic metals, using plants with high potentials for extraction, stabilization and
      hyperaccumulation. This study was conducted in Cameroon, at the Bassa Industrial
      Zone of Douala in 2011, to assess the total content of 19 heavy metals and 5
      other elements in soils and phytoremediation potential of 12 weeds. Partial
      extraction was carried out in soil, plant root and shoot samples.
      Phytoremediation potential was evaluated in terms of the Biological Concentration
      Factor, Translocation Factor and Biological Accumulation Coefficient. The
      detectable content of the heavy metals in soils was Cu:70-179, Pb:8-130, Zn:200
      971, Ni:74-296, Co:31-90, Mn:1983-4139, V:165-383, Cr:42-1054, Ba:26-239, Sc:21
      56, Al:6.11-9.84, Th:7-22, Sr:30-190, La:52-115, Zr:111-341, Y:10-49, Nb:90-172
      in mg kg(-1), and Ti:2.73-4.09 and Fe:12-16.24 in wt%. The contamination index
      revealed that the soils were slightly to heavily contaminated while the
      geoaccumulation index showed that the soils ranged from unpolluted to highly
      polluted. The concentration of heavy metals was ranked as Zn > Ni > Cu > V > Mn >
      Sc > Co > Pb and Cr in the roots and Mn > Zn > Ni > Cu > Sc > Co > V > Pb > Cr >
      Fe in the shoots. Dissotis rotundifolia and Kyllinga erecta had phytoextraction
      potentials for Pb and Paspalum orbicularefor Fe. Eleusine indica and K. erecta
      had phytostabilisation potential for soils contaminated with Cu and Pb,
      respectively.

PMID- 24912227
TI  - A critical review of the arsenic uptake mechanisms and phytoremediation potential
      of Pteris vittata.
AB  - The discovery of the arsenic hyperaccumulator, Pteris vittata (Chinese brake
      fern), has contributed to the promotion of its application as a means of
      phytoremediation for arsenic removal from contaminated soils and water.
      Understanding the mechanisms involved in arsenic tolerance and accumulation of
      this plant provides valuable tools to improve the phytoremediation efficiency. In
      this review, the current knowledge about the physiological and molecular
      mechanisms of arsenic tolerance and accumulation in P. vittata is summarized, and
      an attempt has been made to clarify some of the unresolved questions related to
      these mechanisms. In addition, the capacity of P. vittata for remediation of
      arsenic-contaminated soils is evaluated under field conditions for the first
      time, and possible solutions to improve the remediation capacity of Pteris
      vittata are also discussed.

PMID- 24912228
TI  - Evaluation of copper bioaccumulation and translocation in Jatropha curcas grown
      in a contaminated soil.
AB  - Contamination of soils with copper (Cu) has become a serious problem in the
      environment. Phytoremediation is an emerging green technology that uses green
      plants to remediate heavy metal contaminated areas. This study was conducted to
      evaluate the potential of Jatropha curcasfor remediation of soils contaminated
      with Cu. Seedlings were planted in soils spiked with Cu in amount of 0, 50, 100,
      200, 300, and 400 mg kg(-1) (Cu0, Cu50, Cu100, Cu200, Cu300, and Cu400) for a
      period of five months. The maximum height and number of leaves were recorded in
      control (Cu0) whereas the highest basal stem diameter was found in seedlings
      exposed to Cu50. Copper concentrations among plant parts were in the following
      trend: roots > stems > leaves. The highest total Cu concentration (665 +/- 1 mg
      kg(-1)) and total Cu removal (1.2 +/- 0.2%) based on total plant dry biomass were
      found in Cu400 and Cu50 treatments, respectively. J. curcas exhibited high root
      concentration factor (RCF > 1) and low translocation factor (TF < 1). Although Cu
      accumulation by the plant didn't reach the criteria of Cu hyperaccumulators, this
      species showed a potential to be used in phytostabilization of mildly Cu
      contaminated areas. However, the plant cannot be used for phytoextraction of Cu
      contaminated soils.

PMID- 24912229
TI  - Effects of planting densities on water quality improvements and Pontederia
      cordata's physiology.
AB  - Various planting densities (5, 10, or 20 plants per tank) of Pontederia cordata
      were water-cultivated in purifying tanks to treat polluted water. Seasonal
      effects of the planting densities on the water quality improvement and the
      morphology and physiology of the plant were analyzed. Results indicated that
      planting densities affected the nitrogen and phosphorus removal of water, and the
      morphology and physiology of plants, including activity of peroxidise and
      catalase, content of chlorophyll and soluble protein (SP), the length of root,
      stem and leaf, tiller number and root density. When planting density increased
      from 10 to 20 plants per tank, the morphology and physiology of plants, and the
      nitrogen and phosphorus removal by plants improved slowly, but caused a tiller
      number decline in individual plants. This variation was significant in autumn,
      and associated with seasonal variations of plant physiology. During autumn, there
      were 26 tillers in each plant with 10 plants per tank, compared to 14 tillers per
      plant with 20 plants per tank. Increase in the nitrogen and phosphorus contents
      of the plants for 5-10 plants per tank was 5.41 and 0.79 g kg(-1), compared to
      1.17 and 0.12 g kg(-1) for 10-20 plants per tank, respectively.

PMID- 24912230
TI  - Phytoextraction potential of poplar (Populus alba L. var. pyramidalis Bunge) from
      calcareous agricultural soils contaminated by cadmium.
AB  - To investigate the phytoextraction potential of Populus alba L. var. pyramidalis
      Bunge for cadmium (Cd) contaminated calcareous soils, a concentration gradient
      experiment and a field sampling experiment (involving poplars of different ages)
      were conducted. The translocation factors for all experiments and treatments were
      greater than 1. The bioconcentration factor decreased from 2.37 to 0.25 with
      increasing soil Cd concentration in the concentration gradient experiment and
      generally decreased with stand age under field conditions. The Cd concentrations
      in P. pyramidalis organs decreased in the order of leaves > stems > roots. The
      shoot biomass production in the concentration gradient experiment was not
      significantly reduced with soil Cd concentrations up to or slightly over 50 mg
      kg(-1). The results show that the phytoextraction efficiency of P. pyramidalis
      depends on both the soil Cd concentration and the tree age. Populus pyramidalis
      is most suitable for remediation of slightly Cd contaminated calcareous soils
      through the combined harvest of stems and leaves under actual field conditions.

PMID- 24912231
TI  - Cadmium sorption characteristics of soil amendments and its relationship with the
      cadmium uptake by hyperaccumulator and normal plants in amended soils.
AB  - In order to select appropriate amendments for cropping hyperaccumulator or normal
      plants on contaminated soils and establish the relationship between Cd sorption
      characteristics of soil amendments and their capacity to reduce Cd uptake by
      plants, batch sorption experiments with 11 different clay minerals and organic
      materials and a pot experiment with the same amendments were carried out. The pot
      experiment was conducted with Sedum alfredii and maize (Zea mays) in a co
      cropping system. The results showed that the highest sorption amount was by
      montmorillonite at 40.82 mg/g, while mica was the lowest at only 1.83 mg/g. There
      was a significant negative correlation between the n value of Freundlich equation
      and Cd uptake by plants, and between the logarithm of the stability constant K of
      the Langmuir equation and plant uptake. Humic acids (HAs) and mushroom manure
      increased Cd uptake by S. alfredii, but not maize, thus they are suitable as soil
      amendments for the co-cropping S. alfredii and maize. The stability constant K in
      these cases was 0.14-0.16 L/mg and n values were 1.51-2.19. The alkaline zeolite
      and mica had the best fixation abilities and significantly decreased Cd uptake by
      the both plants, with K > or = 1.49 L/mg and n > or = 3.59.

PMID- 24912232
TI  - Phytoremediation of Pb by Avicennia marina (Forsk.) Vierh and spatial variation
      of Pb in the Batticaloa Lagoon, Sri Lanka during driest periods: a field study.
AB  - Batticaloa Lagoon (Sri Lanka) is subjected to significant pollution as a result
      of anticipated unplanned development works since the cessation of a civil war in
      May, 2009. This paper presents the effectiveness of Avicennia marina (Forsk.)
      Vierh in the phytoremediation of Pb and the variation of Pb in sediments and
      water in the intertidal zone under drier weather conditions. Four pristine areas
      and 4 mangroves cut areas within the Manmunai North Divisional Secretariat
      Division/Batticaloa Municipal Council areas were investigated. Pb levels in the
      sediments and plants were negligible at all locations (i.e., below the method
      detection limit of the AAS for sediments and plants which is 0.25 mg/kg dry
      weight and 0.5 mg/kg dry weight, respectively). However, the water environment
      showed significant contamination (0.17-0.29 mg/L and 0.26-0.34 mg/L in pristine
      areas and cleared areas, respectively), hence Pb bioaccumulation is likely in
      fish and other biota. Avicennia marina is not effective to phytoremediate Pb
      under significant saline conditions.

PMID- 24912233
TI  - Healthy response from chromium survived pteridophytic plant-Ampelopteris
      prolifera with the interaction of mycorrhizal fungus-Glomus deserticola.
AB  - Interaction between arbuscular mycorrhizal fungus Glomus deserticola and
      pteridophytic member Ampelopteris prolifera was found abundant on entire growth
      level based on elemental composition and gaseous exchange as a potential
      remediation system for phytoextraction of chromium. Inoculated A. prolifera (AM)
      and non-inoculated A. prolifera (Non-AM) were supplied with two Cr species: 12
      mmol of trivalent cation (Cr(+3)) [Cr(III)] and 0.1 mmol of divalent dichromate
      anion (Cr2O7(-2)) [Cr(VI)]. Both Cr species were found to be depressed in overall
      growth and inefficient stomatal conductance (g(s)) and net photosynthesis (NP).
      Mycorrhizal association was found to be natural scavenger of Cr toxicity as
      indicated by greater growth in plants exposed to Cr species, and increased gas
      exchange of Cr(III) treated plants. Though, chromium reduction resulted lower
      level of nitrogen (N), phosphorus (P), and potassium (K) but interestingly
      elevated the level of aluminum (Al), iron (Fe), and zinc (Zn) uptake in many
      folds which is the significance of sustainable growth of plant.

PMID- 24912234
TI  - Characterization of bacteria in the rhizosphere soils of Polygonum pubescens and
      their potential in promoting growth and Cd, Pb, Zn uptake by Brassica napus.
AB  - Microbe-enhanced phytoremediation has been considered as a promising measure for
      the remediation of metal-contaminated soils. In this study, two bacterial strains
      JYX7 and JYX10 were isolated from rhizosphere soils of Polygonum pubescens grown
      in metal-polluted soil and identified as of Enterobacter sp. and Klebsiella sp.
      based on 16S rDNA sequences, respectively. JYX7 and JYX10 showed high Cd, Pb and
      Zn tolerance and increased water-soluble Cd, Pb and Zn concentrations in culture
      solution and metal-added soils. Two isolates produced plant growth-promoting
      substances such as indole acetic acid, siderophore, 1-aminocyclopropane-1
      carboxylic deaminase, and solubilized inorganic phosphate. Based upon their
      ability in metal tolerance and solubilization, two isolates were further studied
      for their effects on growth and accumulation of Cd, Pb, and Zn in Brassica napus
      (rape) by pot experiments. Rapes inoculated with JYX7 and JYX10 had significantly
      higher dry weights, concentrations and uptakes of Cd, Pb, Zn in both above-ground
      and root tissues than those without inoculation grown in soils amended with Cd
      (25 mg kg(-1)), Pb (200 mg kg(-1)) or Zn (200 mg kg(-1)). The present results
      demonstrated that JYX7 and JYX10 are valuable microorganism, which can improve
      the efficiency of phytoremediation in soils polluted by Cd, Pb, and Zn.

PMID- 24912235
TI  - Feasibility of Typha latifolia for high salinity effluent treatment in
      constructed wetlands for integration in resource management systems.
AB  - High salinity wastewaters have limited treatment options due to the occurrence of
      salt inhibition in conventional biological treatments. Using recirculating marine
      aquaculture effluents as a case study, this work explored the use of Constructed
      Wetlands as a treatment option for nutrient and salt loads reduction. Three
      different substrates were tested for nutrient adsorption, of which expanded clay
      performed better. This substrate adsorbed 0.31 mg kg(-1) of NH4(+)-N and 5.60 mg
      kg(-1) of PO4(3-)-P and 6.9 mg kg(-1) dissolved salts after 7 days of contact.
      Microcosms with Typha latifolia planted in expanded clay and irrigated with
      aquaculture wastewater (salinity 2.4%, 7 days hydraulic retention time, for 4
      weeks), were able to remove 94% NH(4+)-N (inlet 0.25 +/- 0.13 mg L(-1)), 78% NO2(
      )-N (inlet 0.78 +/- 0.62 mg L(-1)), 46% NO3(-)-N (inlet 18.83 +/- 8.93 mg L(-1))
      whereas PO4(3-)-P was not detected (inlet 1.41 +/- 0.21 mg L(-1)). Maximum
      salinity reductions of 52% were observed. Despite some growth inhibition, plants
      remained viable, with 94% survival rate. Daily treatment dynamics studies
      revealed rapid PO4(3-)-P adsorption, unbalancing the N:P ratio and possibly
      affecting plant development. An integrated treatment approach, coupled with
      biomass valorization, is suggested to provide optimal resource management
      possibilities.

PMID- 24912236
TI  - Bioaccumulation of heavy metals by endemic Viola species from the soil in the
      vicinity of the As-Sb-Tl mine "allchar' Republic of Macedonia.
AB  - Allchar mine is an abandoned arsenic-antimony-thallium deposit located on the
      northwestern part of Kozuf Mt., Republic of Macedonia. Allchar is a unique
      deposit within the world, due to the variety of its mineral composition
      especially and in the high content of thallium. The aim of this work was to
      assess the level of contamination at this post-mining area as well as to
      determine the intensity of accumulation of various elements (Ag, Al, As, Ba, Ca,
      Cd, Co, Cr, Cu, Fe, Ga, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Rb, S, Sb, Sr, Tl, V,
      and Zn) with focus on As, Sb and Tl, in two endemic Viola species from this
      locality (Viola allcharensis G. Beck, Viola arsenica G. Beck) and one Balkan
      endemic species (Viola macedonica Boiss. & Heldr.). Samples of different plant
      parts and soil were digested and then analysed by ICP-AES. It was found that the
      accumulation of As, Sb, and Tl in these endemic species is significantly high. In
      this study a systematic investigation of the As-Sb-Tl contamination of soils and
      their bioavailability was carried out using the extraction procedure in order to
      explore the mobility and potential bioavailability of the As, Sb, and Tl.

PMID- 24912237
TI  - Syrian bean-caper (Zygophyllum fabago L.) improves organic matter and other
      properties of mine wastes deposits.
AB  - The omni-presence of Zygophyllum fabago L. (Syrian bean-caper) natural colonies
      in post mining areas prompted us to investigate its contributions to reclamation
      of mine wastes deposits in southeast Spain. Select plant-related (edaphic)
      characteristics and bio- and water soluble-Cd, Cu, Pb and Zn in rhizosphere of Z.
      fabago were compared to deposits one year since application of pig slurry and
      marble waste. Total N in rhizosphere increased up to a factor of 20X (339 vs 17
      mg N kg(-1)) in El Gorguel and 27X (85 vs 3.1 mg N kg(-1)) in El Lirio sites.
      Organic matter accumulation in rhizosphere from litter and roots of Z. fabago
      increased organic C from 6.6 to 19.5 g kg(-1) in El Gorguel and from 2.1 to 5.7 g
      kg(-1) in El Lirio in one year. Dissolution of inorganic C takes place due to
      organic acids from root exudates of Z. fabago. Reduction in bio-available Cd, Cu,
      Pb, and Zn in rhizosphere of Z. fabago at El Lirio is attributed to increase in
      pH from 5.3 to 7.7 through marble waste addition, although increased cation
      exchange capacity may also have played a role. Addition of marble waste to
      encourage colonization by Z. fabago in acidic mine wastes deposits was
      recommended.

PMID- 24912238
TI  - Phytoextraction potential of wild type and 35S-gshI transgenic poplar trees
      (Populus x Canescens) for environmental pollutants herbicide paraquat, salt
      sodium, zinc sulfate and nitric oxide in vitro.
AB  - Phytoextraction potentials of two transgenic (TR) poplar (Populus x canescens)
      clones TRggs11 and TRlgl6 were compared with that of wild-type (WT) following
      exposure to paraquat, zinc sulfate, common salt and nitric oxide (NO), using a
      leaf-disc system incubated for 21 days on EDTA-containing nutritive WPM media in
      vitro. Glutathione (GSH) contents of leaf discs of TRlgl6 and TRggs11 showed
      increments to 296% and 190%, respectively, compared with WT. NO exposure led to a
      twofold GSH content in TRlgl6, which was coupled with a significantly increased
      sulfate uptake when exposed to 10(-3) M ZnSO4. The highest mineral contents of
      Na, Zn, Mn, Cu, and Mo was observed in the TRggs11 clone. Salt-induced activity
      of catalase enzyme increased in both TR clones significantly compared with WT
      under NaCl (0.75% and 1.5%) exposure. The in silico sequence analyses of gsh1
      genes revealed that P. x canadensis and Salix sachalinensis show the closest
      sequence similarity to that of P. x canescens, which predicted an active GSH
      production with high phytoextraction potentials of these species with indication
      for their use where P. x canescens can not be grown.

PMID- 24912239
TI  - Response of three semi-arid plant species to fluoride; consequences for
      chlorophyll florescence.
AB  - The study was done to investigate the ability of three semi-arid plant species
      viz. Acacia tortilis, Cassia fistula and Prosopis juliflora to adapt to fluoride
      (F) stress. Here we examined the changes in activities of chlorophyll a
      fluorescence and photosynthetic pigment concentration during early growth of
      these plants. One month old plants were treated with 10, 20, and 50 mg kg(-1) F
      in soilrite. We did not observe any major change in photosynthetic performance of
      these plants during early growth. This was revealed by ETR, ETRmax, PPFD-sat and
      deltaF/Fm'-sat values which were higher in these plants. The decrease in chl a,
      chl b and total chl concentrations were significant only at 5 days. For most of
      the parameters, C. fistula was found to be more sensitive to F stress and P.
      juliflora showed least damage from F. The lesser inhibition in the parameters
      reflected the F tolerant nature of these plants with respect to photosynthesis.
      This opens the possibility of potential use of these species for treatment of F
      contaminated soil and water.

PMID- 24912240
TI  - Comparing anthracene and fluorene degradation in anthracene and fluorene
      contaminated soil by single and mixed plant cultivation.
AB  - The ability of three plant species (sweet corn, cucumber, and winged bean) to
      remediate soil spiked with 138.9 and 95.9 mg of anthracene and fluorene per kg of
      dry soil, respectively, by single and double plant co-cultivation was
      investigated. After 15 and 30 days of transplantation, plant elongation, plant
      weight, chlorophyll content, and the content of each PAH in soil and plant
      tissues were determined. Based on PAH removal and plant health, winged bean was
      the most effective plant for phytoremediation when grown alone; percentage of
      fluorene and anthracene remaining in the rhizospheric soil after 30 days were
      7.8% and 24.2%, respectively. The most effective combination of plants for
      phytoremediation was corn and winged bean; on day 30, amounts of fluorene and
      anthracene remaining in the winged bean rhizospheric soil were 3.4% and 14.3%,
      respectively; amounts of fluorene and anthracene remaining in the sweet corn
      rhizospheric soil were 4.1% and 8.8%, respectively. Co-cultivation of sweet corn
      and cucumber could remove fluorene to a higher extent than anthracene from soil
      within 15 days, but these plants did not survive and died before day 30. The
      amounts of fluorene remaining in the rhizospheric soil of corn and cucumber were
      only 14% and 17.3%, respectively, on day 15. No PAHs were detected in plant
      tissues. This suggests that phytostimulation of microbial degradation in the
      rhizosphere was most likely the mechanism by which the PAHs were removed from the
      spiked soil. The results show that co-cultivation of plants has merit in the
      phytoremediation of PAH-spiked soil.

PMID- 24912241
TI  - Constructed wetlands as green tools for management of boron mine wastewater.
AB  - Constructed wetlands are of increasing interest worldwide given that they
      represent an eco-technological solution to many environmental problems such as
      wastewater treatment. Turkey possesses approximately 70% of the world's total
      boron (B) reserves, and B contamination occurs in both natural and cultivated
      sites throughout Turkey, particularly in the north-west of the country. This
      study analyzes B removal and plant uptake of B in pilot plots of subsurface
      horizontal-flow constructed wetlands. Constructed wetlands were vegetated with
      Typha latifolia (referred to as CW1) and Phragmites australis (referred to as
      CW2) to treat wastewater from a borax reserve in Turkey--the largest of its type
      in the world and were assessed under field conditions. The B concentrations of
      water inflows to the systems were determined to be 10.2, 28.2, 84.6, 232.3,
      716.4, and 2019.1 mg l(-1). The T. latifolia in the CW1 treatment group absorbed
      a total of 1300 mg kg(-1) B, whereas P. australis absorbed 839 mg kg(-1). As a
      result, CW1 had an average removal efficiency of 40.7%, while that of CW2 was
      27.2%. Our results suggest that constructed wetlands are an effective, economic
      and eco-friendly solution to treating B mine wastewater and controlling the
      adverse environmental effects of B mining.

PMID- 24912242
TI  - Role of Bacillus licheniformis in phytoremediation of nickel contaminated soil
      cultivated with rice.
AB  - Heavy metal contamination in soil is an important environmental problem and it
      has negative effect on agriculture. Bacteria play a major role in
      phytoremediation of heavy metals contaminated soil. In this study, the effect of
      Bacillus licheniformis NCCP-59, a halophilic bacterium isolated from salt mines
      near Karak, Pakistan, were determined on a three week old greenhouse grown
      seedling and germinating seeds of two rice varieties (Basmati-385 (B-385) and KSK
      282) in soil contaminated with different concentrations (0, 100, 250, 500, and
      1000 ppm) of Nickel. Nickel significantly reduced the germination rate and
      germination percentage mainly at 500 and 1000 ppm. Significant decrease in ion
      contents (Na, K, and Ca) was observed while Ni ion concentration in the plant
      tissues increases as the concentration of Ni applied increases. The
      photosynthetic pigments (chlorophyll a (chl a), chlorophyll b (chl b), and
      carotenoids) were also decreased by the application of different concentrations
      of Ni. Total protein and organic nitrogen were found to be reduced at higher
      concentrations of Nickel. Inoculation of Bacillus licheniformis NCCP-59 improved
      seed germination and biochemical attribute of the plant under Ni stress. It is
      clear from the results that the Bacillus Licheniformis NCCP-59 strain has the
      ability to protect the plants from the toxic effects of nickel and can be used
      for the phytoremediation of Ni contaminated soil.

PMID- 24912243
TI  - Effect of cyclic phytoremediation with different wetland plants on municipal
      wastewater.
AB  - Phytoremediation is a promising cleanup technology for contaminated soils,
      groundwater, and wastewater that is both low-tech and low-cost. The objective of
      this study was to investigate the ameliorative effect of phytoremediation on
      municipal wastewater (MWW). For this purpose, a phytoremediation garden was
      established using different aquatic plants species [Pistia stratiotes, Eichhornia
      crassipess, Hydrocotyle umbellatta, Lemna minor, Tyhpa latifolia, and Scirpus
      acutus] in seven earthen pond systems (P1-P7) for the cyclic treatment of MWW.
      The physico-chemical analysis of MWW was carried out before and after the cyclic
      phytoremediation. Results showed that pH, EC and turbidity of MWW were reduced by
      5.5%, 33.7%, and 93.1%, respectively after treatment (from P1 to P7). Treatment
      system also reduced total dissolved solids (TDS) by 35.2%, Cl by 61%, HCO3 by
      29.2%, hardness by 45.7%, Ca by 32.3% and Mg by 55.9%. Nitrate concentration was
      reduced by 77.6% but SO4 was enhanced slightly. An ameliorative combined effect
      of wetland plants namely L. minor, T. latifolia, and S. acutus on MWW was
      noticed. Sequential phytoremediation with a mixture of plants was more effective
      than that relying only on a single plant species.

PMID- 24912244
TI  - Lead accumulation potential in Acacia victoria.
AB  - To assess the potential of Pb+2 accumulation in different parts of Acacia
      victoria, one year old A. victoria seedlings were exposed to Pb2+(NO3)2 in 5
      different concentrations: 0, 50, 250, 500 and 1000 (mg Pb2+ L(-1)) for 45 days.
      Subsequently, Pb2+ uptake was quantified in roots, shoots and leaves of the
      seedlings by Atomic Absorption Spectroscopy (AAS). In addition, some
      physiological parameters such as biomass production, shoots and roots length,
      plant appearance, tissue concentrations and chlorophyll content were examined.
      Tissue concentrations increased as Pb2+ concentration increased for A. victoria.
      The visible toxicity symptoms (chlorosis and necrosis) appeared only to the
      highest concentration (1000 mg Pb2+ L(-1)), resulting in photosynthesis decrease,
      plant height, root length and dry biomass reduction. Almost 70% (up to 3580 mg
      Kg(-1) of dry tissue) from the Pb2+ was accumulated in the entire plant tissues
      was retained in the roots in the seedlings exposed to 1000 mg Pb2+ L(-1). The
      seedlings accumulated between 403 to 913 mg Kg(-1) of Pb2+ in shoots and 286 to
      650 mg Kg(-1) of Pb2+ in leaves at different treatments. Bioconcentration and
      translocation factors were determined 5.14 and 0.255, respectively. The results
      show that A. victoria is suitable for lead-phytostabilization in Pb(2+) 
      contaminated soil.

PMID- 24912245
TI  - Efficacy of biosolids in assisted phytostabilization of metalliferous acidic
      sandy soils with five grass species.
AB  - The role of sewage sludge as an immobilising agent in the phytostabilization of
      metal-contaminated soil was evaluated using five grass species viz., Dactylis
      glomerata L., Festuca arundinacea Schreb., F. rubra L., Lolium perenne L., L.
      westerwoldicum L. The function of metal immobilization was investigated by
      monitoring pH, Eh and Cd, Pb, and Zn levels in column experiment over a period of
      5-months. Grasses grown on sewage sludge-amendments produced high biomass in
      comparison to controls. A significant reduction in metal uptake by plants was
      also observed as a result of sewage sludge application, which was attributed to
      decreased bioavailability through soil stabilisation. We have observed that the
      sludge amendment decreased metal bioavailability and concentrations in soil at a
      depth of 25 cm, in contrast to untreated columns, where metal concentrations in
      the soil solution were very high.

PMID- 24912246
TI  - Plant uptake and enhanced dissipation of di(2-ethylhexyl) phthalate (DEHP) in
      spiked soils by different plant species.
AB  - This study was conducted to investigate the uptake, accumulation and the enhanced
      dissipation of di(2-ethylhexyl) phthalate (DEHP) spiked in soil (with a
      concentration of 117.4 +/- 5.2 mg kg(-1)) by eleven plants including eight maize
      (Zea mays) cultivars and three forage species (alfalfa, ryegrass and teosinte).
      The results showed that, after 40 days of treatment, the removal rates of DEHP
      ranged from 66.8% (for the control) to 87.5% (for the maize cultivar of Huanong
      1). Higher removal rate was observed during the first 10 days than the following
      days. Plants enhanced significantly the dissipation of DEHP in soil. Enhanced
      dissipation amount in planted soil was 13.3-122 mg pot(-1) for DEHP, and a net
      removal of 2.2%-20.7% of the initial DEHP was obtained compared with non-plant
      soil. The contribution of plant uptake to the total enhanced dissipation was <
      0.3%, and the enhanced dissipation of soil DEHP might be derived from plant
      promoted biodegradation and sorption stronger to the soil. Nevertheless, the
      capability in accumulation and enhanced dissipation of DEHP from spiked soils
      varied within different species and cultivars.

PMID- 24912247
TI  - Ceratophyllum demersum L. and Potamogeton alpinus Balb. from Iset' river, Ural
      region, Russia differ in adaptive strategies to heavy metals exposure--a
      comparative study.
AB  - We examined the uptake of five heavy metals (Cu, Fe, Ni, Zn, and Mn) in
      Ceratophyllum demersum L. (hornwort) and Potamogeton alpinus Balb. (pondweed)
      from Iset' river, Ural region, Russia. This study was conducted in a territory
      that is highly urbanized where the surface waters are contaminated by a wide
      spectrum of pollutants. The environmental situation in this territory drastically
      deteriorated due to anthropogenic activity. The water quality in most of the
      water bodies in the Ural region is rather poor. In a comparative study of C.
      demersum and P. alpinus, differential accumulation pattern was noted for heavy
      metals (HMs). Higher amounts of HMs accumulated in C. demersum compared to P.
      alpinus. Also it was shown that in leaves of C. demersum there were high amount
      of total phosphorus, nitrogen, organics acids and ash; high activity of guaiacol
      peroxidase; high content of nonenzymatic antioxidants viz., flavonoids,
      ascorbate, glutathione and proline; high amount of thiols (soluble and membrane
      bound) compared to P. alpinus.

PMID- 24912248
TI  - Complexation of lead by Bermuda grass root exudates in aqueous media.
AB  - Exudates produced from Bermuda grass roots were collected in deionized water from
      sterilized Bermuda grass sod at 3-day intervals over a period of 15 days.
      Exudates were analyzed for total organic carbon, and characterized via Fourier
      Transform Infrared Spectroscopy. Exudate samples were adjusted to pH values of
      4.5, 6.5, and 7.5, amended with lead and quantified for soluble and complexed
      lead via Inductively Coupled Plasma--Optical Emission Spectrometry. Data obtained
      from total organic carbon measurements indicated compositional changes in Bermuda
      grass root exudates as organic carbon concentrations increased over time.
      Analysis of the infrared spectroscopy data indicated that carboxylic acids and
      amine functional groups were present in root exudates. Also, the ability of root
      exuded compounds to solubilize lead in aqueous media was demonstrated as exudate
      samples dissolved an average of 60% more lead than deionized water. At pH values
      4.5 and 7.5, lead complexation by Bermuda grass root exudates increased with
      decreasing molecular weight size fractions, while an opposite trend was observed
      at pH 6.5. Results from this study demonstrated the ability of Bermuda grass root
      exudates to complex lead in aqueous media.

PMID- 24912249
TI  - [Accessory breast nipple].

PMID- 24912250
TI  - [Interview with minister of health Grohe. "We need general practitioners in the
      field!" (interview by Anno Fricke and Wolfgang van den Bergh)].

PMID- 24912251
TI  - [Lateral entry in the mid 40's. Suddenly a general practitioner!].

PMID- 24912252
TI  - [New executive mandatory insurance physician. KBV has concentrated on itself too
      long].

PMID- 24912253
TI  - [Nearly uncontrollable hyperreactivity. Last options in bronchial asthma].

PMID- 24912254
TI  - [Pathological grief - uncontrollable rage attacks - nocturnal hyperphagia. Is
      that still normal?].

PMID- 24912255
TI  - [Psychosocial risk factors. How does stress affect the coronary arteries?].

PMID- 24912256
TI  - [Youth foreign travel. Dengue and leishmaniasis in the backpack].

PMID- 24912257
TI  - [Patient with atrial fibrillation. Renal colic without kidney stone: what was the
      etiology?].

PMID- 24912258
TI  - [Naturopathy consultation. Helping the sick liver - but naturally!].

PMID- 24912259
TI  - [Smoking cessation improves reflux symptoms].

PMID- 24912260
TI  - [When children won't adhere to inhaled corticosteroids, perhaps the family
      physician to blame].

PMID- 24912261
TI  - [Do all elderly patients really need vitamins and minerals?].

PMID- 24912262
TI  - [The horrors of winter].

PMID- 24912263
TI  - [Hazardous Christmas cake].

PMID- 24912264
TI  - [Formerly children were indeed more fit].

PMID- 24912265
TI  - [Long-term proton pump inhibitor therapy: beware of vitamin B 12 deficiency].

PMID- 24912267
TI  - [Dermatosis: learning for children by watching the adults].

PMID- 24912266
TI  - [A man with lung gout].

PMID- 24912268
TI  - [How infections imprint on skin lesions].

PMID- 24912269
TI  - [Gynecomastia].

PMID- 24912270
TI  - [Molecular allergy diagnostics].

PMID- 24912271
TI  - [Pearly penile papules].

PMID- 24912272
TI  - [Could depression be the cause?].

PMID- 24912273
TI  - [Therapy options against severe COPD].

PMID- 24912274
TI  - [Mechanisms of antiepileptic drugs].

PMID- 24912275
TI  - [Definition and classification of epilepsy].
AB  - The concept or definition of epilepsy was mentioned as a chronic disease of the
      brain consisting of repetitions of EEG paroxysm and clinical seizures caused by
      excessive discharges of the cerebral neurons, in reference with Gastaut's opinion
      and the other statements. Further, we referred to diseases to be excluded from
      epilepsy such as isolated, occasional and subclinical seizures and so on. Next,
      new classifications of seizures and epilepsies were explained on the basis of
      revised terminology and concepts for organization of seizures and epilepsies in
      Report of the ILAE Communication in Classification and Terminology, 2005-09, in
      comparison with the Classification of Epileptic Seizures in 1981 and the
      Classification of Epilepsies and Epileptic Syndromes in 1989.

PMID- 24912276
TI  - [Epidemiology and cause of epilepsy].
AB  - Incidence of epilepsy was estimated at 24-53 per 100,000, while prevalence was
      varying between 2.7-40 per 1,000, in Japan 8.8 in children younger than 13 years.
      Higher incidence and prevalence were increasingly noted in aged population; even
      higher in the advanced aged than in children. Incidence of generalized seizures
      was indicated to be slightly higher than focal seizures, although this figure may
      change due to high incidence of aged epilepsy with increased cerebrovascular
      disorders or degenerative diseases as a cause of epilepsy. Mortality is higher in
      patients with epilepsy than in the general population, including SUDEP in
      intractable epilepsy.

PMID- 24912277
TI  - [GABA(A) receptor trafficking and epilepsy].
AB  - Recent studies clarified a dynamic regulation of the intracellular trafficking of
      GABA(A) receptors and its involvement in the pathophysiology of epilepsy. GABA(A)
      synaptic inhibition decreased in the hippocampal CA1 area of patients with
      intractable temporal lobe epilepsy (TLE). The reduction of GABAergic inhibition
      was accompanied by a decrease in the expression of gephyrin, a scaffolding
      protein, and GABA(A) receptor gamma2 subunit. These findings indicate that the
      reduction of gephyrin impairs the clustering and fixation of GABA(A) receptors in
      postsynaptic membranes, leading to a decrease in number of GABA(A) receptor
      subunits and GABA(A) synaptic inhibition. In contrast, the GABA(A) synaptic
      inhibition was lastingly potentiated in the dentate gyrus of kindled animals and
      the expression of GABA(A) receptor subunits(especially alpha2) was significantly
      increased in TLE patients. It is plausible that the potentiation of dentate
      GABAergic inhibition counteracts a hyperexcitability of granule cells as a
      defense mechanism in epilepsy. In status epilepticus, furthermore, the
      hippocampal GABA(A) receptor beta3 subunits were significantly disphosphorylated,
      resulting in a facilitation of the endocytosis of GABA(A) receptors and reduced
      benzodiazepine sensitivity.

PMID- 24912278
TI  - [Genetic aberrations and epilepsy].
AB  - Despite its frequency in central nervous disease, epilepsy's molecular
      pathogenesis has been unclear. Still, the association of genes causing epilepsy-
      and particular familial epilepsy--have ben ascertained, as having abnormalities
      identified in gene encoding ion channels and receptors. Knowledge of sporadic
      epilepsy, for its part, has been much improved by a next generation sequencer,
      but epilepsy's molecular mechanisms remain uncertain even now, when some 400
      genes have been identified. The identification of genetic abnormalities is,
      nonetheless, helpful in diagnosis, treatment, and counseling for the disease.
      Here, we describe epilepsies in which genetic analyses are useful, the
      contributions made by new technologies, and future prospects in the understanding
      and treatment of epilepsy.

PMID- 24912279
TI  - [Clinical guidelines for epilepsy].
AB  - Many international guidelines for epilepsy from the countries in Europe, USA and
      Asia have been published since the introduction of evidence-based medicine. In
      Japan, the clinical guidelines for epilepsy management were published by the
      Japanese Society of Neurology (JSN) in 2002 and 2010. The clinical guideline for
      epilepsy 2010 primarily targets general practitioners treating epilepsy patients.
      The Japan Epilepsy Society has been publishing 16 guidelines for several topics
      since 2005. The clinical guideline for epilepsy 2010 recommends that
      carbamazepine can be regarded for new onset partial epilepsy and sodium valproate
      is for new onset generalized epilepsy as anti-epileptic drug (AED) monotherapy.
      The new AEDs received approval by the Ministry of Health, Labour and Welfare,
      Japan, mainly in the add-on treatment of adults with partial epilepsy. The
      clinical guideline for epilepsy 2010 will contribute to improvement in the
      management of epilepsy in Japan.

PMID- 24912280
TI  - [Electroencephalography for patient with epilepsy].
AB  - Electroencephalography (EEG) is the primary means by which epileptic activity in
      the brain is measured. The frequency of epileptic discharges is influenced by
      vigilance and biological rhythms. When checking for epileptic activity using EEG,
      measurements must be repeated and recordings made during sleep are recommended if
      epileptic discharges do not readily appear. Epileptic discharges must be
      classified as generalized or focal discharges, and discriminated from non
      epileptic discharges such as vertex sharp transients, positive occipital sharp
      transients, 14 & 6 positive spike discharge, and artifacts. Attention should be
      paid to small sharp spikes, 6Hz spike and slow wave, focal slow waves, and
      generalized rhythmic slow waves, which should all be considered variants of
      epileptic activity. EEG provides information regarding focal and generalized
      brain dysfunction in addition to epileptic activity. Because the misreading of
      EEG may negatively affect the lives of patients, reading the EEG correctly is
      quite important.

PMID- 24912281
TI  - [MRI and CT in the diagnosis of epilepsy].
AB  - MRI and CT are important for the diagnosis and treatment of epilepsy. Diffusion
      weighted images are particularly useful for detecting early changes in the brain.
      In this article, I reviewed radiological findings associated with seizures
      (reduced diffusion and swelling of hippocampus and cortex, and a reversible
      splenial lesion), and lesions causing epilepsy and seizures, such as congenital
      abnormality of the brain (holoprosencephaly, hemimegalencephaly, lissencephaly,
      heterotopia, polymicrogyria, schizencephaly, and focal cortical dysplasia),
      neurocutaneous syndromes (tuberous sclerosis and Sturge-Weber syndrome), vascular
      disorders (moyamoya disease/syndrome and cavernous angioma), and
      encephalitis/encephalopathy (herpes encephalitis, anti-NMDA receptor
      encephalitis, acute necrotizing encephalopathy of childhood, and acute
      encephalopathy with biphasic seizures and late reduced diffusion).

PMID- 24912282
TI  - [PET, SPECT, and MEG in the diagnosis of epilepsy].
AB  - Morphological imaging tools, such as MRI and CT, are now recommended to be
      carried out in all patients with epilepsy. However, no lesion is sometimes
      visualized on MRI in location related epilepsy patients, further neuroimaging
      tools are required for presurgical evaluation. In order to identify epileptic
      focus, PET, SPECT and MEG have been proposed as clinically relevant tools. These
      are useful and reliable examinations in clinical routine as well as for research
      purpose. Their ability to image in vivo changes in brain biochemistry has
      provided valuable insights into the epileptogenesis, seizure propagation and
      termination. In future, further progression in the sensitivity and spatial
      resolution of each examination will probably increase the clinical role in the
      assessment of patients with epilepsy.

PMID- 24912283
TI  - [Genetic diagnosis for epilepsy].
AB  - Very few epilepsy phenotypes have been associated with causative genes;
      nevertheless, it is becoming possible, for some epilepsy phenotypes, to predict
      the most efficacious anti-epileptic drugs for patients based on their genetic
      makeup. The development of individualized medicine based on genetic information
      and the genetic diagnosis of epilepsy are expected to greatly improve the
      diagnosis and treatment of epilepsy. We developed DNA array(resequencing-array)
      for genetic diagnosis of epilepsy, and successfully identified epilepsy mutations
      in patients. This finding indicates that this DNA array is likely to be a useful
      tool in clinical settings at least for screening purposes, because it can
      simultaneously and efficiently detect several gene mutations in a patient.

PMID- 24912284
TI  - [Differential diagnosis of epilepsy].
AB  - Epilepsy may cause convulsion or transient loss of consciousness. Differential
      diagnosis of convulsion includes acute symptomatic seizure, psychogenic
      nonepileptic seizure, and epilepsy. Long duration of seizure, fluctuating course,
      and asynchronous movements favor psychogenic nonepileptic seizures. Occurrence of
      seizure from EEG-confirmed sleep, postictal confusion, and stertorous breathing
      favor epileptic seizures. Differential diagnosis of transient loss of
      consciousness includes syncope, epilepsy, and hypoglycemia. Causes of syncope
      include vasovagal syncope, arrhythmia, and orthostatic hypotension.

PMID- 24912285
TI  - [Treatment of pediatric epilepsy].
AB  - Recently, the treatment strategy for pediatric epilepsy has been dramatically
      changed in Japan, because of the approval of new-generation antiepileptic drugs.
      Since 2006, a total of 6 new antiepileptic drugs, including gabapentin (GBP;
      adults/pediatric patients: 2006/2011 [year of approval]), topiramate (TPM;
      2007/2013), lamotrigine (LTG; 2008/2008), levetiracetam (LEV; 2010/2013),
      stiripentol (STP; 2012/2012), and rufinamide (RUF; 2013/2013), have been
      introduced. Thus far, valproate (VPA) and carbamazepine (CBZ) have been first
      indicated for "generalized" epilepsy and "focal" epilepsy syndromes/types,
      respectively, in Japan. However, the approval of these new drugs could allow us
      to choose more effective and less toxic ones at an early stage of treatment. In
      this chapter, we describe the latest domestic and foreign guidelines for the
      treatment of pediatric epilepsy.

PMID- 24912286
TI  - [Treatment of epilepsy in patients of adolescence and adulthood].
AB  - For treatment of epilepsy in patients of adolescence and adulthood, we always
      take into account all the 3 aspects of 1) diagnosis of seizure type and epilepsy
      syndrome, 2) existence of comorbidity and 3) interaction between concomitant
      drugs, and thus an appropriate treatment approach is individualized. The first
      line antiepileptic drug (AED) used for focal seizure or epilepsy is
      carbamazepine, and the first line AED for generalized seizure or epilepsy is
      valproic acid. If monotherapy with these drugs is insufficient, it is recommended
      to change to another drug or to add other drugs. For add-on therapy, the
      interaction between drugs should be considered. If polytherapy with these drugs
      is insufficient, diagnosis are again carefully checked, and further examination
      for resective epilepsy surgery or vagus nerve stimulation is considered.

PMID- 24912287
TI  - [Treatment of epilepsy in the elderly].
AB  - As the elderly constitute the most rapidly growing population, epilepsy in this
      group is an important health issue worldwide. We identified 70 patients who
      developed epilepsy after the age of 65 years at our institution. Complex partial
      seizures (CPS) without secondarily generalization were most frequent. The most
      frequent diagnosis was temporal lobe epilepsy. Etiological diagnosis was possible
      in nearly 50% patients, including those with cerebrovascular disease. Interictal
      EEG revealed focal epileptiform discharges in 66.7% of patients. Forty-two
      patients were on antiepileptic monotherapy and 52 patients had been seizure-free
      for more than 1 year. Epileptogenecity was relatively low in elderly patients and
      they responded well to antiepileptic medication.

PMID- 24912288
TI  - [Management of reproductive-age women with epilepsy].
AB  - Medical treatment of epilepsy is quite different for women than for men. It is
      known that estrogen facilitates while progesterone inhibits the generation of
      epileptic seizures. Due to the direct neuronal effects of estrogen, progesterone,
      and their metabolites, as well as the cyclical nature of sex hormone release,
      women are particularly susceptible to the effects of these hormones on seizure
      frequency and severity. Antiepileptic drugs (AEDs) may result in reproductive
      endocrine disorders, decreased effects of oral contraceptives, or congenital
      malformations. On the other hand, if AED treatment is insufficient, seizures may
      influence reproductive endocrine disorders or cause fetal death. Physicians
      should minimize these risks through preconception counseling and appropriate
      treatment of women with epilepsy who are of reproductive age.

PMID- 24912289
TI  - [Dietary therapy of epilepsy].
AB  - Reappraisal of ketogenic diets (KD) were delayed in Japan compared to USA and
      Korea. The reasons are unknown, but possible explanations are (1) Japanese food
      culture prefers rice and less fat and (2) ACTH therapy is preferred for West
      syndrome in Japan. Since Japanese child neurologists were surprised at dramatic
      effects on glucose transporter 1 deficiency syndrome (Glut-1DS) in 2003, KD have
      been slowly accepted for treatment of epilepsy in Japan. New generation KD
      including modified Atkins diet (mAD) are preferred to classical KD. KD can be
      causal therapy in Glut-1DS and some of mitochondrial disorders, though anti
      epileptic drugs are symptomatic therapy. KD can alleviate intractable seizures in
      epilepsies with brain malformation in addition to West syndrome and Dravet
      syndrome, etc. KD may work for brain tumor, cancer, neurodegenerative disorders
      including Alzheimer's disease. C7-8 triglycerides or fatty acid esters are under
      development as medicines replacing KD.

PMID- 24912290
TI  - [Cutting edge of surgical treatment for epilepsy].
AB  - Epilepsy surgery is indicated for drug-resistant epileptic seizures. Resective
      surgery for mesial temporal lobe epilepsy associated with localized lesions has
      become an established and recommended treatment that achieves abolishment of
      disabling seizures in 80% of patients. However, surgical outcome of resective
      surgery for nonlesional and neocortical epilepsies are not satisfactory. For
      these patients, various approaches are being promoted including development or
      modification of surgical procedures represented by disconnective surgery,
      multiple subpial and hippocampal transection, introduction of better analysis
      methods of EEG for localization of epileptic foci and functional areas, and
      neuromodulation treatments including by vagus nerve stimulation, deep brain
      stimulation and closed-loop electrical stimulation.

PMID- 24912291
TI  - [Biofeedback treatment for epilepsy].
AB  - Pharmacological treatment is the mainstay for the treatment of epilepsy. However
      concerns regarding long-term side effects of drugs are increasingly voiced.
      Behavioral treatments including biofeedback, represents an alternative management
      option for the control of epilepsy. Biofeedback is a non-invasive bio-behavioral
      procedure through which patients can learn to gain psychophysiological control
      over seizures. This article will first overview seizure precipitation from a
      psychological perspective, and then introduce three major biofeedback treatments.
      Sensory motor rhythm (SMR) and slow cortical potential(SCP) biofeedback uses
      electroencephalographic parameters and are categorized as neurofeedback.
      Electrodermal activity (EDA) biofeedback focuses on modulation of peripheral
      sympathetic tone. The neural mechanisms underlying biofeedback treatment will be
      discussed in relation to thalamo-cortical regulation(of neural excitability
      across brain networks).

PMID- 24912292
TI  - [Treatment of status epilepticus].
AB  - Status epilepticus is defined as epileptic seizure with the duration for over 30
      min or clustered seizure without complete recovery of consciousness for 30 min or
      more. From the management point of view, therapeutic intervention is recommended
      for prolonged seizures for 5 min or more. Intranasal, buccal or intramuscular
      administration of midazolam is strongly evidence-based and highly recommended
      method for the treatment of prolonged seizures before the intravenous access.
      Diazepam or midazolam is the first choice as initial intravenous treatment.
      Intravenous bolus administration of fosphenytoin or phenobarbital is the second
      line treatment. General anesthesia using such as thiopental or propofol is
      indicated for refractory status epileptic, which should be managed in the
      intensive care unit.

PMID- 24912293
TI  - [Therapeutic strategy for mental symptoms in people with epilepsy].
AB  - Epilepsy has an association with nearly all types of psychiatric problems and
      psychiatric symptoms are common clinical manifestations seen in epilepsy
      patients. For example, interictal depression in individuals with epilepsy is more
      prevalent than in the general population or among patients with other chronic
      disorders. The high frequency of depression and clinical impact of psychosis in
      epilepsy have been well documented in recent studies, indicating the importance
      of diagnosing and treating psychiatric implications in affected patients. This
      article reviews various psychiatric symptoms such as postictal psychosis,
      interictal psychosis, depression, psychogenic non-epileptic seizure(PNES), and
      cognitive dysfunction encountered in patients with epilepsy.

PMID- 24912294
TI  - [Adverse effects of antiepileptic drugs].
AB  - Adverse effects of antiepileptic drugs are classified into idiosyncratic adverse
      effects, pharmacology-related adverse effects and biological effect after
      modification of seizure frequencies. Pharmacology-related adverse effects include
      those by administered AED and those by mutual interactions. Stevens-Johnson
      syndrome, one of the idiosyncratic adverse effects, may be predicted by the
      intrinsic HLA type (e.g., A*31:01 for CBZ). In epileptic patients after acute
      encephalitis, cutaneous adverse reactions usually occur in a month after
      encephalitis, but some patients will tolerate the causative AED by the extremely
      slow re-introduction. Prevention of pharmacology-related adverse effects needs
      therapeutic drug monitoring, and slow introduction considering dose-response
      curves for AEDs. Genotype examination of CYP2C9 and 2C19 can contribute to the
      safe introduction of PHT.

PMID- 24912295
TI  - [Sleep disorders and epilepsy].
AB  - It has been reported that patients with epilepsy often have insomnia and/or
      daytime sleepiness; the symptomatologic features differ in seizure types. Not
      only the administration of anti-epileptics, but also inappropriate sleep hygiene
      cause daytime sleepiness. In subjective assessment of sleepiness, we need to pay
      attention if it can correctly assess or not. The prevalence of obstructive sleep
      apnea in patients with epilepsy is approximately 10-30%. Sleep apnea deteriorates
      the seizure control because of worsen sleep condition by sleep apnea, especially
      in elderly patients. Some researchers report that continuous positive airway
      pressure was effective for seizure control. Patients with epilepsy occasionally
      have REM sleep behavior disorder as comorbidity. Examination using
      polysomnography is required for differential diagnosis.

PMID- 24912296
TI  - [Epilepsy and dementia].
AB  - Japan is experiencing an increase in the number of dementia patients, and the
      incidence of epilepsy is high among the elderly. A survey, from 2007 to 2012, of
      279 epilepsy patients admitted to our hospital's neurology department showed that
      newly-onset epilepsy occurred more frequently in elderly patients. Of 153 elderly
      patients with epilepsy, aged 65 years and older, 31(20.2%) had dementia as an
      underlying disease. Although the prevalence of epilepsy in dementia is varied,
      higher brain dysfunctions are known to occur as a result of epilepsy. Considering
      such symptoms as epilepsy with higher brain dysfunction (E-HBD) would enable
      clinical investigation without overlooking higher brain dysfunctions that have
      effective treatments.

PMID- 24912297
TI  - [New antiepileptic drugs: characteristics and clinical applications].
AB  - New antiepileptic drugs (AEDs) that have been used in many other countries for
      more than 10 years have only recently became available for use in Japan.
      Gabapentin, topiramate, lamotrigine and levetiracetam were licensed for use in
      Japan between 2006 and 2010. Stiripentol for Dravet syndrome and rufinamide for
      Lennox-Gastaut syndrome were also approved in 2012 and 2013 as orphan drugs.
      Clinical trials of other new AEDs such as oxcarbazepine, vigabatrin, lacosamide,
      and perampanel are in progress. In this review, the general characteristics of
      the new AEDs are discussed with regards to their effectiveness, tolerability,
      drug interaction, safety and mechanisms of action. The effectiveness, of the new
      AEDs compared with established AEDs is also discussed. Clinical applications of
      the new AEDs, focusing on gabapentin, topiramate, lamotrigine and levetiracetam
      are also discussed based on our domestic experience as well as overseas reports.

PMID- 24912298
TI  - [Epilepsy and driving].
AB  - In Japan, the Road Traffic Act was amended in June 2013, including new penalty to
      false statement in a disease condition declaration form, and new voluntary
      notification system for a doctor who is aware that a person is at high risk for
      traffic accident and in possession of a driver license. Moreover, New Criminal
      Law Act was established in November 2013, including a prison sentence of up to 15
      years for persons, who under the influence of specific drugs or diseases, causing
      death or injury to other persons by driving a motor vehicle. Both laws are
      supposed to be enforced during 2014, after additional resolutions including the
      review of the laws after five years, considerations so as not to create
      discrimination due to diseases, etc are examined.

PMID- 24912299
TI  - [Epilepsy care network].
AB  - Build-up of community health coalition system is now an essential part of
      medicine. However, little attention has been paid to epilepsy care in Japan,
      which resulted in a chaotic and difficult situation to find epilepsy-care
      physicians in the community. The reason is that responsible medical specialty in
      charge has been ambiguous historically in Japan and a lack of post-in-charge in
      the government to plan epilepsy care system is aggravating this condition. To
      solve this issue, epilepsy care network connecting the primary, secondary and
      tertiary epilepsy care physicians should be established and open to the
      community. In this context, our Epilepsy Care Network-Japan was started on July
      2012 proposing a new epilepsy care algorithm suitable for our complex medical
      community.

PMID- 24912300
TI  - [Moving from pediatric to adult care of epilepsy: improving transitions].
AB  - The common problems faced by adult patients with epilepsy are different from
      those facing pediatric patients. When adults with epilepsy work, marry, and give
      birth, they must deal with problems that they never experienced in childhood,
      such as gaining drivers licenses and accessing various medical and welfare
      services, in addition to the potential complications involved with their disease.
      Therefore, medical transitions from pediatric to adult care of epilepsy are
      crucial to ensuring that patients have a high quality of life. To solve the
      underlying problems that can block efficient transitions, we propose cooperation
      not only between pediatric neurologists and adult neurologists but between these
      practitioners and those from other disciplines, such as psychiatrists. We also
      argue that collaboration among relevant societies and national education programs
      is necessary.

PMID- 24912301
TI  - [ASK1-MAP kinase signaling pathway as a therapeutic target for human diseases].
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a serine/threonine kinase
      belonging to the mitogen-activated protein kinase (MAPK) kinase kinase family.
      ASK1 is activated in response to various stresses, such as reactive oxygen
      species (ROS), tumor necrosis factor (TNF) alpha, lipopolysaccharide (LPS) and
      endoplasmic reticulum (ER) stress, and plays pivotal roles in a wide variety of
      cellular responses, including cell death, differentiation and inflammation.
      Recent studies have shown that ASK1-MAPK signaling pathway has key roles in human
      diseases induced by the dysfunction of cellular stress responses. In this review,
      we provide an overview of the current understanding of ASK1 as a potential
      therapeutic target for human diseases.

PMID- 24912302
TI  - [Expanded indication of National Health Insurance for H. pylori associated
      gastritis].
AB  - Since National Health Insurance covered eradication therapy for H. pylori
      infected gastritis, all patients with H. pylori infection could be received
      eradication under insurance. Cure of H. pylori infection improves histological
      gastritis, also atrophic change, and intestinal metaplasia. Prevention of H.
      pylori associated diseases such as gastric cancer is expected. According to
      Insurance instruction, it is carried out in order of endoscopic diagnosis of
      chronic gastritis, diagnosis of H. pylori infection, and eradication treatment.
      Endoscopic examination prior to H. pylori diagnosis is necessary for screening of
      gastric cancer. Endoscopic finding of RAC (regular arrangement of collecting
      venules) in the angle of stomach suggests lack of infection with H. pylori,
      disappearance of RAC suspects H. pylori infection.

PMID- 24912303
TI  - [Insomnia disorder comorbid with diabetes].
AB  - Insomnia disorder is one of the most prevalent conditions comorbid with diabetes
      and has been shown to have a possible role in the development of diabetes.
      Insomnia is characterized by a state of excessive physiological and cognitive
      arousal with alterations in autonomic and hypothalamic-pituitary-adrenal
      function. The chronic neuroendocrine activation in insomnia may predispose
      insomniacs to the development of metabolic disorders including glucose
      intolerance. In contrast, diabetic complications, in combination with the
      disruption of a sleep-wake homeostatic and circadian process, can be key factors
      precipitating insomnia symptoms and involve several subtypes of insomnia.
      Furthermore, inappropriate lifestyles are also likely responsible for the
      exacerbation of insomnia and diabetes. Thus, the pathogenesis of insomnia
      disorder and diabetes could mutually interact to develop each disease with a
      vicious cycle, accounting for the high comorbidity between the diseases.

PMID- 24912304
TI  - Foreword. Allergen products for diagnosis and therapy: regulation and science.

PMID- 24912305
TI  - History of specific immunotherapy.

PMID- 24912306
TI  - Legal status and regulation of allergenic products in the United States.

PMID- 24912307
TI  - Regulation of allergen products in Europe (including NPPs).

PMID- 24912308
TI  - Current status and regulation of allergen products in Mexico.

PMID- 24912309
TI  - Regulation of allergen products in Canada: an overview of the current and the
      proposed regulatory frameworks (draft guidance).

PMID- 24912310
TI  - Current and future challenges for the allergen manufacturers.

PMID- 24912311
TI  - Update on the FDA/CBER allergen standardization program.

PMID- 24912312
TI  - Validation of major allergen references and ELISAs--current state of the BSP090
      project.

PMID- 24912313
TI  - Molecular and functional characterization of natural allergen extracts.

PMID- 24912314
TI  - The potential of mass spectrometry as a novel tool in standardization of natural
      allergen extracts.

PMID- 24912315
TI  - Efficacy testing of allergen mixtures for specific immunotherapy.

PMID- 24912316
TI  - Biomarkers of tolerance in response to allergen immunotherapy.

PMID- 24912317
TI  - Multiplex IgE antibody testing as a tool for diagnosis and defining the allergic
      (atopic) status of study populations.

PMID- 24912318
TI  - Environmental exposure units for specific immunotherapy trials.

PMID- 24912319
TI  - Physicochemical characterisation of mite allergoids and alum-adsorbed mite
      allergoids.

PMID- 24912320
TI  - Physicochemical characterization of recombinant allergens and hypoallergenic
      variants.

PMID- 24912321
TI  - Antibody-based assays for potency determination of mite allergoids and for
      stability studies of alum-adsorbed mite vaccines.

PMID- 24912322
TI  - An overview of proposed mechanisms of specific immunotherapy (SIT).

PMID- 24912323
TI  - Mechanisms of immunotherapy specific to the sublingual or oral route.

PMID- 24912324
TI  - Oral immunotherapy for food allergy.

PMID- 24912325
TI  - Interleukin-5+ super-effector Th2 cells as targets for immunotherapy and drug
      discovery.

PMID- 24912326
TI  - Use of Trichuris suis ova (TSO) therapy for the treatment of allergy.

PMID- 24912327
TI  - Current status of subcutaneous and sublingual immunotherapy with recombinant
      allergens.

PMID- 24912328
TI  - Recombinant allergens for SIT of mite allergy.

PMID- 24912329
TI  - Recombinant allergens for SIT of cat allergy.

PMID- 24912330
TI  - Targeting antibody receptors as an approach towards immunotherapy.

PMID- 24912331
TI  - Toll-like receptor ligands as adjuvants in allergy vaccines.

PMID- 24912332
TI  - Adjuvants and vector systems for the sublingual route.

PMID- 24912333
TI  - Structural studies of allergens suggest hypotheses for immune system
      interactions.

PMID- 24912334
TI  - Sublingual immunotherapy: overview of American experience.
AB  - SLIT remains under investigation in the United States. It is anticipated that
      many patients, who suffer from intermittent (seasonal) or persistent (perennial)
      allergic rhinitis, would be interested in SCIT as an immunomodulatory therapy.
      Not all of the future SLIT patients seek professional advice for diagnosis and
      treatment of allergic rhinitis or have so previously and are dissatisfied with
      the necessity to use or cannot tolerate pharmacotherapy. Effective SLIT (as for
      SCIT) requires an accurate diagnosis of IgE mediated allergic rhinitis or asthma,
      and it is well known that many patients are not correct when predicting what
      their own allergies are. The same goes for some general practice health care
      professionals as well!

PMID- 24912335
TI  - SLIT clinical trials for allergic rhinitis in the U.S.

PMID- 24912337
TI  - SIT for the treatment of atopic dermatitis.

PMID- 24912336
TI  - The politics and economics of specific immunotherapy across Europe.

PMID- 24912338
TI  - [Jorge Leon Arguedas (1916 December 9 -2013 June 5].

PMID- 24912339
TI  - [The invalidity of the impact factor as indicator of the impact of Latin American
      scientific journals].
AB  - Use of the Impact Factor is currently being discarded in industrialized countries
      where, to name one case, up to 40% of the articles published in Nature are never
      cited, despite the high Impact Factor of that journal. However, it is still used
      in Latin America to evaluate journals and authors, potentially influencing who
      are given positions and who receives funding. To find out how valid the Impact
      Factor is for Latin American research, 1 used the database BINABITROP to see how
      much of the relevant literature was used to measure impact. I found that the
      Science Citation Index (SCI) excluded 96% of the relevant literature when
      measuring the impact of biological articles about Costa Rica for the studied year
      (2011). Therefore, the impact of Latin American science is unknown and the Impact
      Factor should not be used to assess how often a journal, institution or author
      are cited.

PMID- 24912340
TI  - On Limnocytherina axalapasco, a new freshwater ostracod (Podocopida:
      Limnocytheridae) from Mexican crater lakes.
AB  - Limnocytherina is a genus conformed by 12 species; its distribution in the
      American continent is known to be exclusively on the North (neartics), but little
      is reported about its distribution from Mexico (transition zone) and Central
      America (Neotropics). Different sampling campaigns were undertaken in three
      crater lakes from the Axalapascos region in east-central Mexico, during 2008,
      2009 and 2011. As a product of these campaings, the new species of Limnocytherina
      axalapasco was found, which displays some intraspecific variability among
      populations. In this study, we described the taxonomy, the habitat, the
      ecological preferences and the larval development of this new species. A total of
      10 sediment samples (8 littoral, 2 deepest point) were collected from lakes
      Alchichica, La Preciosa and Quechulac. We found that L. axalapasco is closely
      related to two North American species: L. posterolimba and L. itasca as well as
      one Central American species L. royi comb. nov. With the inclusion of L.
      axalapasco and L. royi to the genus, the distribution of Limnocytherina is
      extended to Central America. The four most important distinguishing characters of
      this new species are: 1) valve surface and margins covered with small, spine-like
      projections; 2) most of the A1 setae with a highly developed setule at distal
      part, producing a bifurcate appearance; 3) the upper ramus on the hemipenis is
      elongated, and by far overpasses dorsal/distal margins, distal lobe is triangular
      and short, while the hook-like process is prominent, outward orientated, and
      overpassing the tip of the distal lobe; 4) the UR is moderately developed with
      seta f3 elongated and setae f1 and f2 short. Considering its ecological
      characteristics and larval development, L. axalapasco was preferably found in
      alkaline waters dominated by Cl(-) or HCO3(-) and Na+ or Mg2+, temperatures
      ranging between 19.1 to 20.3 degrees C, and dissolved oxygen concentrations from
      5 to 6.5 mg/L. This species was abundant in deeper (approximately 64m) areas of
      the saline Alchichica lake, where surface water displayed conductivity values of
      up to 2 250 microS/cm, and the sand with low percentage of silt resulted the
      preferred substrate. Along with the description of L. axalapasco, we provide
      additional information on the hemipenis of L. itasca, L. royi and L.
      sanctipatricii, and we discuss on the Limnocytherina-type of hemipenis.

PMID- 24912341
TI  - Distribution and additive partitioning of diversity in freshwater mollusk
      communities in Southern Brazilian streams.
AB  - Additive partitioning of species diversity is a promising approach for analyzing
      patterns of diversity in mollusk communities, especially their spatial
      distribution. Our aims were to assess the distribution of mollusk communities in
      Southern Brazilian streams, and to evaluate the partitioning of community
      diversity at different spatial scales. The study was carried out in the lower
      course of the Toropi River, one of the main tributaries of the Ibicui River
      Basin, in Southern Brazil. Four microbasins were considered: Sertao da Mata,
      Ribeirao, Tororaipi and Chiniqua, and sampling were undertaken in autumn, April
      and May 2009. Six sites were sampled in each stream: two in 1st-order segments,
      two in 2nd-order segments, and two in 3rd-order segments. All species found and
      the community as a whole, exhibited a clumped distribution. However, the variance
      to-mean ratios for the Drepanotrema kermatoides and Heleobia bertoniana were
      higher than those of other species, suggesting a higher degree of aggregation.
      The additive partitioning of the species richness showed that the observed
      richness at smallest scale (alpha=within streams) represented 20.7%, and among
      streams (beta1) represented 10.5% of the total richness. The richness and Shannon
      diversity index observed at the alpha scale, were higher than those observed at
      the first level of beta diversity scale (beta1=among-streams). The interaction
      between passive dispersal, tolerance to changes in some environmental variables,
      abiotic factors, and clumped distribution might have determined the spatial
      distribution of the communities studied. The greatest variation at the larger
      scales of analysis, involving among-orders and among-microbasins (beta2 and
      beta3, respectively) components, was expected, considering that the increase in
      distance leads to greater differences in richness (higher beta diversity). In
      conclusion, our results showed that the clumped distribution influenced the
      partition of the diversity of the mollusk communities in the streams studied.
      Dispersal methods and tolerance to variations in abiotic factors also have
      important roles in determining high alpha diversity. The partitioning of
      diversity showed that to preserve limnetic mollusks, it is important to preserve
      local areas, i.e., streams. Accordingly, conservation of streams on a local scale
      will contribute to conservation of the entire basin and maintenance of regional
      diversity (gamma).

PMID- 24912342
TI  - Growth parameters and density variation of a queen conch, Strombus gigas
      (Neotaenioglossa: Strombidae), population from Xel-Ha park, a marine protected
      area.
AB  - The queen conch, Strombus gigas, is a gastropod of commercial importance in the
      Caribbean. Population studies are based on size frequency analysis, using either
      length or weight parameters for the whole live organism. This contribution used
      mark-recapture data to estimate the Von Bertalanffy equation parameters and
      population number variation within a non harvest population from a protected
      area, to clarify the biometric parameters that better suit for the whole
      population, or for the juvenile and adult fractions. Conchs from Xel-Ha Park were
      monthly sampled from November 2001 to August 2005. Every conch found was measured
      and marked with a numbered tag that identified month and locality; and monthly
      abundance was estimated with Jolly's method. Length, lip thickness and weight
      increments were used to estimate the Von Bertalanffy growth equation parameters
      with Appeldoorn's subroutine of FISAT program. The population number varied
      through the study, with a minimum of 49 in April 2003 and maximum of 9 848 during
      June 2005. Conchs make only temporary use of Xel-Ha cove. Shell length gave the
      best fit for the juvenile fraction: L(infinity)=251, K=0.3, C=0.8 Wp=0.3; and lip
      thickness for adults: L(infinity)=47.78, K=0.17, C=0.1, Wp=0.86, while, the whole
      population was better represented by weight: L(infinity)=3850, K=0.36, C=0.8,
      Wp=0.3. A maximum age of 19 years was estimated from the population. Natural
      mortality was 0.49/year for juveniles and 0.29/year for adults. There were two
      pulses of recruitment: fall-winter and summer. It is concluded that population
      studies from length frequency data, should be analyzed independently in two
      groups, shell for the juvenile fraction and lip thickness for the adult fraction,
      or if it is not possible to analyze the population fractions separately, weight
      should be used to avoid miss calculation of the age structure.

PMID- 24912343
TI  - Seasonal variation in body size and diet of the sea star Astropecten marginatus
      (Paxillosida, Astropectinidae) off coast of Parana, Southern Brazil.
AB  - The sea star Astropecten marginatus has a neotropical distribution and is a
      highly abundant and frequent species in shrimp trawling by-catchin many places
      along the Brazilian coast. This has caused its threat to extinction and in
      addition, its bio-ecological aspects are poorly known. Thus, the main objective
      of this study was to analyze the seasonal variations of population length
      structure and feeding habits of the sea stars A. marginatus inhabiting off state
      of Parana, Southern Brazil. The analyzed specimens were collected in February
      (summer), April (fall), June (winter) and October (spring) of 2008 from shrimp by
      catch trawling. In the laboratory, each individual had its length measured and
      then weighed on an analytical scale. Afterwards, the stomach contents of 10
      individuals of each of two most frequent length classes were seasonally analyzed.
      The relative frequency and abundance for each prey category was determined and,
      then combined into an index of alimentary importance. A total of 994 individuals
      of A. marginatus were collected with length ranging from 7.0 to 56.2mm, but most
      individuals were in the 20.1-25mm length classes. Individuals larger than 40mm
      were only collected in the spring while a few recruits (<10mm) were found in fall
      and winter. The total weight of individuals ranged from 0.1 to 15.3g and the
      weight-length relationships showed a negative allometric growth (b<2.54).
      Regarding its food consumption, this sea star explored eleven food items, with
      cumaceans and mollusks as the most frequent items. High frequency of empty
      stomach was recorded at fall. Seasonal differences in the amount explored preys
      and ingested items as well as in the prey composition were also observed. Higher
      amount of explored prey categories and ingested items were recorded at winter
      spring than summer-fall periods. Predominance in prey category changed from
      gastropods (summer and fall) to cumaceans (winter and spring). The importance of
      gastropods as main prey category at summer and fall should be carefully
      considered since it was coincidently observed with high frequency of empty
      stomach and low amount of ingested items. The observed seasonal differences in
      feeding behavior pattern were mainly associated to low prey availability and to
      changes in the sea star feeding rates, and probably reflected in some biological
      traits such as small body size of the population inhabiting waters off the Parana
      coast, Southern Brazil.

PMID- 24912344
TI  - Intertidal benthic macrofauna of rare rocky fragments in the Amazon region.
AB  - Rock fragment fields are important habitat for biodiversity maintenance in
      coastal regions, particularly when located in protected areas dominated by soft
      sediments. Researches in this habitat have received surprisingly little attention
      on the Amazon Coast, despite rock fragments provide refuges, nursery grounds and
      food sources for a variety of benthic species. The present survey describes the
      mobile macroinvertebrate species composition and richness of the intertidal rocky
      fragments in Areua Island within the "Mae Grande de Curuca" Marine Extractive
      Reserve (RESEX) on the Brazilian Amazon Coast. Samples were collected during the
      dry (August and November 2009) and rainy seasons (March and May 2010) on the
      upper and lower intertidal zone, using a 625cm2 quadrat. At each season and
      intertidal zone, macroinvertebrate samples were collected along four transects
      (20m each) parallel to the waterline, and within each transect two quadrats were
      randomly sampled. Macroinvertebrates were identified, density determined, and
      biomass values obtained to characterize benthic diversity from the rocky
      fragments. The Jackknife procedure was used to estimate species richness from
      different intertidal zones during the dry and rainy seasons. Macrofaunal
      community comprised 85 taxa, with 17 "unique" taxa, 40 taxa were common to both
      intertidal zones and seasons, and 23 taxa have been recorded for the first time
      on the Brazilian Amazon Coast. Species richness was estimated at 106 +/- 9.7 taxa
      and results suggest that sampling effort was representative. Polychaeta was the
      most dominant in species number, followed by Malacostraca and Gastropoda.
      Regarding frequency of occurrence, Crustacean species Dynamenella tropica,
      Parhyale sp. and Petrolisthes armatus were the most frequent representing >75% of
      frequency of occurrence and 39 taxa were least frequent representing <5% of
      frequency of occurrence. Occurrence of crustaceans and polychaetes were
      particularly noteworthy in all intertidal zones and seasons, represented by 15
      and 13 taxa, respectively. The most representative class in abundance and biomass
      was Malacostraca that represented more than half of all individuals sampled, and
      was dominated by Petrolisthes armatus. The latter was one of the most frequent,
      numerous and higher biomass species in the samples. In general, results indicated
      greater richness and biomass in the lower zone. Additionally, richness and
      density increase during the rainy season. Rock fragment fields in Areua Island
      are rich in microhabitats and include a diverse array of species in a limited
      area. Our results underline the importance of rock fragment fields in Areua
      Island for the maintenance of biodiversity in the Amazon Coast.

PMID- 24912345
TI  - On the ecology of the cursorial spider Odo bruchi (Araneae: Zoridae) in a
      grassland natural reserve from central Argentina.
AB  - The "Ernesto Tornquist" Provincial Park (ETPP) is located inside the Ventania
      system (Argentina) and was created to protect one of the last relicts of pampean
      grasslands. Even though many studies have looked at the vertebrate faunal
      diversity, biology, and conservation in this Park, few studies have been
      dedicated to arthropods. Among these, spiders have been used as ecological
      indicators to evaluate nature conservation status, nevertheless, basic
      information on their distribution and ecology is necessary for their use as
      indicator taxa in this region. Thus the goal of this study was to present the
      phenology and demography of the spider Odo bruchi, a cursorial spider present in
      the ETPP. For this, spiders were sampled bimonthly using pitfall traps between
      September 2009-2010 (first year), and March 2011-2012 (second year). A total of
      10 traps were placed every 10m along a transect of 100m parallel to the longest
      axis ofa grassland slope with native vegetation. Traps were filled with 1 500mL
      of ethylene glycol, that were examined and refilled every 60 day period. We
      collected a total of 799 specimens in two years. Juveniles were the most abundant
      reaching 47.8% of the total, while males corresponded to 27.8% and females 24.4%.
      We found significant differences in the mean abundance of O. bruchi: the
      abundance during spring-summer (Nov-Dec-Jan-Feb) was significantly higher than
      the other periods of the two years period. Moreover, we found an even abundance
      distribution throughout the year in the entire study. This work represents one of
      the first contributions to the ecology of this spider family in the area. Also,
      our results comprise relevant information to encourage future studies on this
      spider species as a bio-indicator of the conservation status of pampean
      grasslands.

PMID- 24912346
TI  - [Characterization of the behavioral and vibrational signals in Euthyrhynchus
      floridanus (Hemiptera: Pentatomidae) during courtship and copulation].
AB  - Euthyrhynchus floridanus (Linnaeus) (Hemiptera: Pentatomidae) is a neotropical
      species belonging to the family Pentatomidae with over 4 000 species described,
      and is distributed from Florida to Brazil. This study describes the sexual
      behavior and reported for the first time the production of substrate vibrations
      by males and females during copulatory behavior and mating. Courtship and
      copulatory behavior, as well as the diverse signals, were recorded with a
      phonographic cartridge connected to a video camera. Female vibrations were
      reproduced in the absence of females and the responses by males were recorded. At
      least three types of substrate vibrations were distinguished in males and one in
      females, and these signals were characterized by their low frequency, varying
      from 127 to 180Hz. The sounds of E. floridianus males were significantly
      different in frequency, duration and number of pulses, both in courtship and in
      copulation, for the purring and drumming sounds. The production of sounds in this
      species is associated principally with mechanical, stimulatory behavior during
      courtship and copulation. Patterns of behavior and their relation to substrate
      vibrations suggest that these signals are important for the males in the context
      of mate location and sexual selection.

PMID- 24912347
TI  - Reproductive strategies of two Neotropical killifish, Austrolebias vandenbergi
      and Neofundulus ornatipinnis (Cyprinodontiformes: Rivulidae) in the Bolivian Gran
      Chaco.
AB  - The dry Chaco, a semiarid thorn forest, is experiencing some of the highest
      deforestation rates globally, coupled with the fact that small-bodied fish are at
      the highest risk of extinction, the killifish inhabiting this region may be some
      of the most threatened taxa. Yet, aspects of ecology and life history for
      Neotropical killifishes in the Bolivian Gran Chaco region are completely lacking,
      and basic life-history data is of critical importance for the design and
      implementation of conservation measures. Collections were conducted during the
      early (January 2011) and late (March-April 2011) rainy season using an area-based
      sampler and dip net surveys. Fish standard length and body depth were measured as
      well as the number of oocytes per size class, mean oocyte diameter per size
      class, and total fecundity for the females of each species. A total of 490
      specimens of rivulids were captured; Austrolebias vandenbergi: 85 females, 105
      males and 39 juveniles, and N. ornatipinnis: 62 females, 113 males, 86 juveniles.
      Sexual size dimorphism, absolute fecundity, oocyte developmental stages, oocyte
      diameter, and population sex ratios were determined for each species. Both
      species exhibited sexual size dimorphism. Male A. vandenbergi exhibited longer
      standard length (mean +/- SD; males: 27.07 +/- 3.89mm, females: 23.6 +/- 2.02mm)
      and body depth (males: 8.9 +/- 1.7mm, females: 7.2 +/- 1.1 mm) as compared to
      females. Male N. ornatipinnis had a similar pattern for both standard length
      (males: 26.0 +/- 7.1mm, females: 19.1 +/- 5.83mm) and body depth (males: 5.6 +/-
      1.9mm, females: 4.7 +/- 1.0mm). Austrolebias vandenbergi had fewer and smaller
      oocytes per female (47 +/- 31.6) than N. ornatipinnis (206 +/- 131.2). There was
      a positive relationship between fecundity and female body size in both species.
      The presence of multiple developmental stages of oocytes (immature, maturing, and
      mature) suggest that both species of rivulids exhibit fractional spawning, a
      reproductive strategy that enhances reproductive success in these extreme
      habitats. Neofundulus ornatipinnis exhibited a higher mean oocyte diameter for
      all three developmental stages (immature, maturing, and mature) as compared to A.
      vandenbergi. Austrolebias vandenbergi exhibited an equal adult sex ratio
      (males:females, 1:1), but there was a slight female biased ratio for N.
      ornatipinnis (males:females, 1:1.8). These results provide fundamental and
      valuable information for ensuring rivulid conservation in tropical regions, and
      also improve the knowledge on the biology and ecology of these poorly known
      species. To our knowledge, this study represents the first contribution on the
      reproductive biology of two Neotropical annual rivulid fishes (Austrolebias
      vandenbergi and Neofundulus ornatipinnis) inhabiting semi-permanent and ephemeral
      ponds in the Gran Chaco of Southeastern Bolivia.

PMID- 24912348
TI  - Detection of morphometric differentiation in Sattar snowtrout, Schizothorax
      curvifrons (Cypriniformes: Cyprinidae) from Kashmir Himalaya using a truss
      network system.
AB  - Schizothorax curvifrons is a morphometrically and meristically most variable and
      economically valuable promising fish food from Kashmir Valley. Since there is a
      lack of information on stock structure of wild populations on this species, this
      study was aimed to investigate the intraspecific variation of this important
      snowtrout. For this, two rivers and one lake in Kashmir Himalaya were sampled
      from January 2011 to October 2012. Fish body measurements were taken and
      morphometric characters using the truss network system was constructed.
      Altogether, 506 fish specimens were collected. Data were subjected to principal
      component analysis, discriminant function analysis and univariate analysis of
      variance. The first principal component explained 63.44% of total variation,
      while second and third components explained 8.34% and 5.31%, respectively. The
      step-wise discriminant function analysis retained two variables that
      significantly discriminated the populations. Using these variables 83.4% of the
      original specimens were classified into their correct groups and 81.1% of the
      cross-validated (leave one out procedure) specimens were classified into their
      correct groups. All of the total 31 transformed truss measurements exhibited
      highly significant (p<0.001) differences between the populations. This represents
      the first attempt on stock structure of S. curvifrons; therefore, this study will
      hopefully guide fisheries taxonomists about its current stock structure and would
      help in its management and conservation programme across Kashmir Himalaya area.

PMID- 24912349
TI  - [Species and size composition of fishes in Barra de Navidad lagoon, Mexican
      central Pacific].
AB  - Coastal lagoons are considered important nursery areas for many coastal fishes.
      Barra de Navidad coastal lagoon (3.76km2) is important for local economy as it
      supports tourism development and artisanal fisheries. However, the role of this
      lagoon in the dynamics of coastal fish populations is scarcely known. Thus, the
      objectives of this research were: to characterize the water of the lagoon and
      related weather conditions, to develop a systematic list of the ichthyofauna, and
      to estimate the proportion of juveniles in the total number of individuals
      captured of most abundant species. Water and fish samples were collected between
      March 2011 and February 2012. Physical and chemical variables were measured in
      rainy and dry seasons. Several fishing gears were used including a cast net,
      beach purse seine and gillnets of four different mesh sizes. Our results showed
      that the lagoon is most of the time euhaline (salinity 30-40ups), although it can
      be mixopolyhaline (salinity 18-30ups) during short periods. Chlorophyll and
      nutrients concentrations suggested eutrophication in the lagoon. Mean water
      temperature changed seasonally from 24.9 degrees C (April, high tide) to 31.4
      degrees C (October, low tide). Considering ichthyofauna species, a total of 36
      448 individuals of 92 species were collected, 31 of them adding up to 95% of the
      total of individuals caught. Dominant species were Anchoa spp. (44.6%), Diapterus
      peruvianus (10.5%), Eucinostomus currani (8.1%), Cetengraulis mysticetus (7.8%),
      Mugil curema (5.2%) and Opisthonema libertate (4.5%). The lagoon is an important
      juvenile habitat for 22 of the 31 most abundant species. These included several
      species of commercial importance such as snappers (Lutjanus argentiventris, L.
      colorado and L. novemfasciatus), snook (Centropomus nigrescens) and white mullet
      (Mugil curema). Other four species seem to use the lagoon mainly as adults. This
      paper is the first contribution on the composition of estuarine ichthyofauna in
      Jalisco State, and it also constitutes the more complete reference on the
      detailed size composition of a set of dominant species in a coastal lagoon in the
      central Mexican Pacific.

PMID- 24912350
TI  - [Environmental heterogeneity and its relationship with diversity and abundance of
      the fish community in a coastal system of Gulf of Mexico].
AB  - The coastal lagoons of Veracruz, Gulf of Mexico, include a great variety of
      biological resources. These resources, especially fish communities, have been
      barely described and that require more ecological studies. With this aim, this
      investigation analyzed the spatial and temporal variation of diversity, abundance
      and assemblages of the fish community and its relationship with physical-chemical
      parameters of the Chica-Grande coastal system. For this, eight defined sites were
      monthly sampled for water characteristics and fish community composition (10min
      hauls of 1 500m2 a shrimp trawl net), between September 2005 and November 2006.
      The spatial-temporal variation of physical-chemical parameters, allowed the
      definition of two contrasting environments according to salinity, temperature,
      transparency, dissolved oxygen and depth gradients. A total of 1 947 fishes were
      collected for a total weight of 57.88kg. From these, 22 species, 20 genera and 14
      families were identified; and four species were new records for the system. As it
      was detected for the physical-chemical conditions, the diversity of the fish
      community also showed a spatial gradient, with high values (H'=2.37, D=3.35,
      J'=0.82) in the brackish habitat, and low ones in freshwater environments. Fish
      abundance did not show such a marked gradient response, however, it was higher in
      the freshwater habitat. The highest diversity (H'=2.05) and species richness
      (D=2.99) was recorded during the North winds ("nortes") months (November
      February), while density and biomass were higher (0.034 ind./m2, 1.42g/m2) during
      the rainy months (July-October). The Importance Value Index (IVI) defined six
      dominant species accounting for 77.8% of the fish abundance and 87.9% of total
      catch by weight. The Canonical Correspondence Analysis (CCA) showed that the fish
      habitat relationship was explained by 68% of total variance for the two first
      axes, where salinity, transparency and temperature changes were the most
      important environmental variables in determining the fish community composition
      and distribution. In this study, spatial gradients of environmental variables
      explained the changes in fish species composition and abundance; while the
      temporal gradients, the fish community structure and its relationship with
      seasonal patterns of habitat use by the species during their life cycles.

PMID- 24912351
TI  - [Population ecology of Crocodylus acutus (Reptilia: Crocodylidae) in Palmasola
      lagoon, Oaxaca, Mexico].
AB  - Population ecology of Crocodylus acutus (Reptilia: Crocodylidae) in Palmasola
      lagoon, Oaxaca, Mexico. Abundance and population structure are important
      parameters to evaluate and compare the conservation status of a population over
      time in a given area. This study describes the population abundance and structure
      of Crocodylus acutus in Palmasola lagoon, Oaxaca. The field works consisted of
      night surveys during the new moon phase, between the 21:00 and 24:00h. These were
      conducted during the dry and wet seasons and counted the number of individuals to
      obtain population estimates. Recorded encounter rates ranged from 32 to
      109.3ind./ km in 40 journeys deployed with an average time of 18 minutes
      browsing. The estimated population size using the Messel's model ranged from 32.7
      to 93 individuals. For both seasons, there was a marked dominance of subadults,
      followed by juveniles and to a lesser extent adult individuals, as well as
      undetermined individuals (i.e. unknown body/size/length), in both seasons. There
      was also a significant association with mangrove areas (26.1%) by juveniles; the
      subadults's individual use of superficial water (22.7%) and mangrove areas
      (15.7%); meanwhile the adults were observed on superficial water (9.7%). This
      information contributes to our understanding of the population ecology of C.
      acutus in the Palmasola lagoon where the estimated population size seems to show
      higher values when compared to other reports in the country.

PMID- 24912352
TI  - Reproductive biology of Pleurodema guayapae (Anura: Leptodactylidae:
      Leiuperinae).
AB  - Pleurodema guayapae is a species that inhabits saline environments and semidesert
      zones from central Argentina. To date, the knowledge about the reproductive
      biology of this species is very poor, and our aim is to contribute to its
      knowledge with the description of some important reproductive aspects. For this,
      field work was undertaken in an area near to Patquia, La Rioja province. Sampling
      was undertaken during three summer periods (2006-2007; 2007-2008; 2008-2009) in
      Chamical-Patquia area, where we could find reproductively active populations. We
      observed and described breeding sites, type of clutch, process of foam nest
      construction, clutch and egg number and sizes, and hatching time and stage.
      Behaviour observations were performed from the time that males began to call
      until the pairs ended up the foam nests building, and layed the eggs.
      Additionally, one amplected pair was observed and filmed in the process of foam
      nest construction, and four amplectant pairs were collected and separatelly
      placed in plastic containers, for nests observations in the laboratory. Hatching
      time was based on three different foam nests of known age. We found that P.
      guayapae populations were acoustically active only after a rainfall. Its breeding
      sites were represented by ephemeral ponds of fresh water, product of rains. The
      males emitted their calls inside or outside these ponds. A detailed description
      of the foam nest construction process by both females and males was made. The
      clutches were in dome-shaped foam nest type of 6-9cm in diameter and 1-3cm in
      height, some of which were in communal nests. The nests had an average of 1 137
      pigmented eggs. This species showed a short hatching time. Our results allow us
      to conclude that this species should be considered an extreme explosive breeder.
      Our results are discussed with others obtained for related species.

PMID- 24912353
TI  - [Reproductive ecology of Geobatrachus walkeri (Anura: Strabomantidae)].
AB  - Geobatrachus walkeri is a frog that belongs to a monotypic genus and is endemic
      to the Sierra Nevada de Santa Marta, Colombia. The species inhabits different
      microhabitats between 2 000 to 3 500m altitude, including the leaf litter of a
      pine plantation. To understand its reproductive ecology, we conducted eight frog
      samplings, covering the rainy and dry seasons, and two habitat types (secondary
      native forest and pine plantation) during 2010-2011. For this study, we also
      included data obtained from five previous similar samplings undertaken during
      2008-2009. The pine leaf litter was the main microhabitat where frogs were found;
      we heard choruses of six-ten calling males during all sampled months, and
      observed the frogs having diurnal and nocturnal activity. Regardless of the year
      of study, the population consisted of neonates recruited several times of the
      year, a large number of juveniles with a wide range of body sizes, and fewer
      adults with a narrower range of body size. The histological analyses of the
      gonads showed that the size at maturity was near 18mm SVL for males and females,
      and those adult males and females were reproductive active during all sampling
      months, suggesting a continuous reproductive activity pattern. However, during
      the dry season, the seminiferous tubules showed a drastically diminished
      spermatic epithelium although containing abundant luminal spermatozoa, which
      suggest a reduction in the sperm production at the end of this season. Similarly,
      frogs of all age categories were significantly more abundant during the early dry
      season, whereas were significantly less abundant with the advancement of the
      dryness suggesting that the intensity of the dry season could temporally stop the
      activity and reproduction of this population.

PMID- 24912354
TI  - [Geographic data for Neotropical bats (Chiroptera)].
AB  - The global effort to digitize biodiversity occurrence data from collections,
      museums and other institutions has stimulated the development of important tools
      to improve the knowledge and conservation of biodiversity. The Global
      Biodiversity Information Facility (GBIF) enables and opens access to biodiversity
      data of 321 million of records, from 379 host institutions. Neotropical bats are
      a highly diverse and specialized group, and the geographic information about them
      is increasing since few years ago, but there are a few reports about this topic.
      The aim of this study was to analyze the number of digital records in GBIF of
      Neotropical bats with distribution in 21 American countries, evaluating their
      nomenclatural and geographical consistence at scale of country. Moreover, we
      evaluated the gaps of information on 1 degrees latitude x 1 degrees longitude
      grids cells. There were over 1/2 million records, but 58% of them have no
      latitude and longitude data; and 52% full fit nomenclatural and geographic
      evaluation. We estimated that there are no records in 54% of the analyzed area;
      the principal gaps are in biodiversity hotspots like the Colombian and Brazilian
      Amazonia and Southern Venezuela. In conclusion, our study suggests that available
      data on GBIF have nomenclatural and geographic biases. GBIF data represent
      partially the bat species richness and the main gaps in information are in South
      America.

PMID- 24912355
TI  - [Effects of landscape and vegetation structure on the diversity of phyllostomid
      bats (Chiroptera: Phyllostomidae) in Oaxaca, Mexico].
AB  - The tropical forest fragmentation is known to affect the spatial structure of the
      landscape and habitat. These alterations can modify the attributes of bat
      assemblages, however, this phenomenon has been little studied and understood. In
      this work we evaluated the structure of landscape (i.e. composition and
      configuration) and vegetation, and its relationship with assemblage- and
      population-level characteristics of phyllostomid bats in a tropical rainforest of
      Southeastern Mexico. For this, we previously selected 12 sites located in
      continuous and fragmented forests, where bats were captured using mist nets
      during a two years sampling effort (144 nights). Bats relative abundance, species
      richness (diversity of order 0, 0D), Shannon diversity index (1D) and Simpson
      index (2D) were evaluated in all sites, and their relationship with seven
      measures of landscape structure and seven measures of vegetation structure was
      described using a Hierarchical Partitioning Analysis. A total of 1 840
      individuals of 29 species of phyllostomid bats were captured in this period.
      Differences in the assemblages were manifested only in the relative abundance and
      not in the richness of the species. The assemblages of fragmented forest
      exhibited greater variation in species composition and a greater abundance of
      frugivorous and nectarivorous bats in comparison with the assemblages of
      continuous forest. The landscape configuration was related to the assemblage- and
      population-level attributes, contrasting with previous studies where the
      composition was a key element. At habitat level, tree density and canopy cover
      determined the abundance of bats. Nectarivorous and frugivorous bats were mostly
      found in disturbed vegetation landscapes, primarily due to landscape
      configuration (e.g. edge density). This phenomenon could be a response to the
      availability of food in primary and intermediate successional stages, which are
      characterized by an abundance of food value.

PMID- 24912356
TI  - Nupela species (Naviculales: Bacillariophyceae) from Colombian lowland waters
      including N. acaciensis nov. sp. and N. catatumbensis nov. sp.
AB  - The genus Nupela comprises ca. 50 species that generally have a distribution
      restricted by bioclimatic frontiers. As part of an integrated analysis of the
      diatom flora of Colombia, in this study we focused our interest on the genus
      Nupela from lowland waters. Periphyton samples were collected from 150 sites of
      lotic water bodies in Colombia, taking into account hidrogeomorfological
      variability. In each sampling station, periphyton samples were obtained by
      scraping, and temperature, pH, dissolved oxygen and conductivity variables were
      measured. Samples were processed by both light microscopy (LM; Carl Zeiss Axio
      Scope.A1) and scanning electron microscopy (SEM; FEI-Quanta 450 and a Jeol JSM
      6360 LV). The genus Nupela was found in 28 sites. Five taxa were identified,
      described and illustrated from tropical or subtropical environments: N.
      lesothensis, N. praecipua y N. subpallavicinii; these were new records for
      Colombia, and N. acaciensis and N. catatumbensis two new species for science. N.
      acaciensis is characterized by raphe branches of both valves equally long
      combined with cymbelloid symmetry, striae built by 2 transapically elongated
      areolae that delimit a longitudinal line at each hemivalve. N. catatumbensis is
      characterized by the presence of a well developed raphe in both valves; valves
      lanceolate with subcapitated to capitated ends and cymbelloid symmetry, striae
      built by 3-4 transapically elongated areolae, interestriae elevated as
      transapical ribs and internal proximal raphe ends hook-shaped. The genus Nupela
      was widely distributed in the studied basins but showed different distribution
      patterns: N. acaciensis and N. subpallavicini had a restricted distribution,
      while N. catatumbensis, N. lesothensis and N. praecipua had a wider distribution,
      and were collected in sites with significant variations in their ecomorphology,
      altitude, temperature, pH and electrolyte content.

PMID- 24912357
TI  - [Ecogeography of the genus Sticta (lichenized Ascomycota: Lobariaceae) in
      Colombia].
AB  - Colombia is a megadiverse country, but with a substantial gap in the taxonomic
      and ecological knowledge of fungi and lichens. Thus, the objective of the present
      study was an ecogeographical analysis of the Sticta species in Colombia. The data
      included macrodistribution (with respect to mountain ranges and life zones) and
      microhabitat preferences (light, substrate) and were obtained from field work and
      herbarium collection labels (completed by comparison with modern geographic and
      vegetation maps), for 103 species of Sticta currently recognized in Colombia
      (plus seven additional biotypes with different photobionts or reproductive mode).
      Using non-metric multidimensional scaling (NMS), correlations between
      ecogeographical variables and species were established, and ecotypes were
      delimited. Colombian species of Sticta showed distinct distribution patterns
      relative to altitude, mountain ranges, life zones, as well as light exposure and
      substrate, forming several distinct groups. Cyanobacterial species tend to have
      wider distribution ranges than green algal species. We concluded that the orogeny
      of the Northern Andes substantially affected speciation of the genus Sticta and
      its ecogeographical differentiation.

PMID- 24912358
TI  - [Ontogeny of the sporangium, spore formation and cytochemistry in Colombian
      Lycopodials (Lycopodiaceae)].
AB  - Studies on reproductive aspects of Lycopodiaceae are not very abundant in the
      scientific literature, and constitute essential information to support taxonomic
      and systematic relationships among the group. Here we present a detailed study of
      the ontogeny of sporangia and sporogenesis, and the chemical determination of
      several compounds generated during spore formation. The analyses were performed
      in 14 taxa of six genera of the family, Diphasiastrum, Diphasium, Huperzia (a
      genus which is treated here including Phlegmariurus), Lycopodiella, Lycopodium
      and Palhinhaea. Specimens were collected in three departments from the Colombian
      Andes between 1 454-3 677m altitude. Ontogeny was studied in small, 1cm long
      pieces of strobili and axis, which were fixed in glutaraldehyde or FAA,
      dehydrated in alcohol, embedded in LR White, sectioned in 0.2-0.5 microm and
      stained with toluidine blue (TBO), a metachromatic dye that allows to detect both
      sporopollenin and lignin or its precursors, during these processes. For other
      studies, paraplast plus-embedded sections (3-5 microm) were stained with safranin
      fast green and alcian blue-hematoxylin. Chemical tests were also conducted in
      sections of fresh sporangia at different stages of maturity using alcian blue
      (mucopolysaccharides), Lugol solution (starch), Sudan III (lipids),
      phloroglucinol (lignin) and orcein (chromosomes). Sections were observed with
      photonic microscope equipped with differential interference contrast (DIC) and
      fluorescence microscopy (for spore and sporangium walls unstained). Strobili and
      sporangia were dehydrated with 2.2 dimethoxypropane, critical point dried and
      coated with gold for scanning electron microscopy (SEM). Our results indicated
      that the ontogeny of sporangia and sporogenesis were very similar to the
      previously observed in Huperzia brevifolia. Cutinisation occurs in early stages
      of development of sporangium cell walls, but in their final stages walls become
      lignified. As for the sporoderm development, the exospore is the first layer
      formed, composed by sporopollenin. The endospore deposits as a thin inner layer
      composed of cellulose, pectin and carboxylated polysaccharides. The perispore, if
      present, deposits at last. Mucopolysaccharides were found on the sporocyte coat
      and its abundance in sporangial cavity persists up to the immature tetrads stage,
      and then disappears. The lipids were abundant in the sporocytes, tetrads and
      spores, representing the main source of energy of the latter. In contrast, starch
      is not detected in the spores, but is abundant in premeiotic sporocytes and
      immature tetrads, developmental stages of high cellular metabolic activity.
      Intrinsic fluorescence corroborates the presence of lignin and cutin in the
      sporangium wall, while the sporopollenin is restricted to the exospore. The
      transfusion cells and the perispore are not always present. However, the
      processes of ontogeny and sporogenesis are extremely similar throughout the taxa
      studied, suggesting that they represent conservative family traits, nonspecific
      or generic.

PMID- 24912359
TI  - In vitro propagation of Cyathea atrovirens (Cyatheaceae): spore storage and
      sterilization conditions.
AB  - Cyathea atrovirens occurs in a wide range of habitats in Brazil, Paraguay,
      Uruguay and Argentina. In the Brazilian State of Rio Grande do Sul, this commonly
      found species is a target of intense exploitation, because of its ornamental
      characteristics. The in vitro culture is an important tool for propagation which
      may contribute toward the reduction of extractivism. However, exogenous
      contamination of spores is an obstacle for the success of aseptic long-term
      cultures. This study evaluated the influence of different sterilization methods
      combined with storage conditions on the contamination of the in vitro cultures
      and the gametophytic development of C. atrovirens, in order to establish an
      efficient propagation protocol. Spores were obtained from plants collected in
      Novo Hamburgo, State of Rio Grande do Sul, Brazil. In the first experiment,
      spores stored at 7 degrees C were surface sterilized with 0.5, 0.8 and 2% of
      sodium hypochlorite (NaClO) for 15 minutes and sown in Meyer's culture medium.
      The cultures were maintained in a growth room at 26 +/- 1 degrees C for a 12-h
      photoperiod and photon flux density of 100 micromol/m2/s provided by cool white
      fluorescent light. Contamination was assessed at 60 days, and gametophytic
      development was scored at 30, 60, 120 and 130 days of in vitro culture, analyzing
      300 individuals for each treatment. There was no significant difference in
      culture contamination among the different sodium hypochlorite concentrations
      tested, and all treatments allowed for the development of cordiform gametophytes
      at 130 days of culture. In the second experiment, spores stored at 7 and -20
      degrees C were divided into two groups. Half of the spores were surface
      sterilized with 2% of NaClO for 15 minutes and the other half was not sterilized.
      All spores were sown in Meyer's medium supplemented with one of the following
      antibiotics: nystatin, Micostatin and actidione. The culture conditions and the
      procedures used for evaluating contamination and gametophytic development were
      the same described for the first experiment. No contamination was observed in
      spores stored at -20 degrees C and treated with NaCIO and actidione. In all
      treatments, cordiform gametophytes presenting antheridia were observed at 120
      days. The percentages of these gametophytes increased from 120 to 130 days and no
      significant differences were observed among treatments. Archegonia were observed
      on cordiform gametophytes at 130 days. The findings provide data relevant to in
      vitro propagation procedures of this species, which may increase the availability
      of plants for ornamental purposes, therefore contributing to the reduction of the
      exploitation of endangered tree ferns species.

PMID- 24912360
TI  - Reproductive success and genetic diversity of Psychotria hastisepala (Rubiaceae),
      in fragmented Atlantic forest, Southeastearn Brazil.
AB  - The impacts of forest fragmentation on both reproductive biology and genetic
      diversity of native plant species is hardly understood, despite some studies have
      analyzed this current worldwide problem. Since this constitutes one of the main
      threats to seasonal semi-deciduous forests in Southeastern Brazil, we
      investigated the reproductive success and the genetic diversity of a distylous,
      understory shrub (Psychotria hastisepala) within this context of forest
      fragmentation. For this study, a set of seven forest fragments of sizes ranging
      from 4.1 to 168.7 hectares were chosen. The intervenient matrix comprised
      pastures (25-50%), monocultures (33-50%) and rural roads and buildings (14
      28.5%). Overall, 91 plants (54 for the short-styled morph and 37 for the long
      styled morph; mean of 6.5 plants per fragment) were investigated. To evaluate
      reproductive success, we quantified fruit and seed production under natural
      pollination; to evaluate genetic diversity and population structure, we employed
      ISSR markers on genomic DNA. Plants with the short-styled morph exhibited a
      significantly higher reproductive success than those with the long-styled morph;
      there was no association between seed production and size of the forest fragment.
      Levels of genetic diversity were positively associated with the number of plants
      per fragment; but they were not related to flower morph. AMOVA showed that about
      65% of the overall genetic variation was attributed to the differences between
      plants within fragments. The results suggested that populations of P. hastisepala
      were susceptible to decline owing to forest fragmentation.

PMID- 24912361
TI  - Awn length variation and its effect on dispersal unit burial of Trachypogon
      spicatus (Poaceae).
AB  - Trachypogon spicatus, formerly known as Trachypogon plumosus, is a dominant grass
      in some savannas of Northern South America. Its dispersal unit, like many other
      species of the Andropogoneae tribe, bears a hygroscopic awn which facilitates its
      establishment in favorable microsites. Some authors have previously proposed that
      there is a positive correlation between awn length and dispersal unit burial, and
      that this relationship increases the probability of seed survival in the event of
      a fire, since soil acts as insulator. In this study we experimentally tested this
      relationship for T. spicatus. A total of 192 diaspores were placed in randomized
      blocks, in aluminum trays filled with soil under greenhouse conditions. Diaspores
      were sprayed with water daily for a month to guarantee awn movement; on the last
      day of the experiment, they were sprayed with red aerosol paint to determine
      burial depth. The effects of awn length, presence of caryopses, and presence of a
      pivot for the passive segment of the awn on diaspore burial were evaluated.
      Germination viability was tested using a tetrazolium salt test for 35 caryopses.
      No significant differences in diaspore burial were observed between diaspores
      with and without caryopses (F(2,126) = 0.034, p=0.853). A positive correlation
      between awn length and diaspore burial was observed only if the passive awn
      lacked a pivot (r(66)=0.394, p<0.05). Diaspores whose awns had a pivot point
      achieved significantly deeper burial distances than their counterparts
      (F(2,126)=7.063, p=0.005). Viability test found that 0% of caryopses tested were
      able to germinate; this is possibly due to the time difference between sampling
      and testing. We considered the presence or absence of caryopsis as an important
      factor, since previous studies have not yet considered it and the high production
      of sterile diaspores in grasses. These results suggest that the physical
      mechanism behind T. spicatus diaspore burial is awn torque. This would explain
      why our results partially support the hypothesis previously proposed by other
      authors regarding the effect of awn length upon dispersal unit burial, but would
      also account for the differences observed in burial depth between diaspores with
      an available pivot point for the passive awn and diaspores lacking thereof.

PMID- 24912362
TI  - [Terrestrial flora of Malpelo Island, Colombia, Eastern Tropical Pacific].
AB  - Malpelo Island is located 380km off the mainland continental coast of Colombia,
      in the Pacific Ocean. Several geological, ecological, and zoological studies,
      both marine and terrestrial, have been conducted in this island. Despite some
      marginal comments on some publications, no single specific survey has been
      devoted to botany so far. In order to make a floristic inventory of the
      terrestrial flora of this island, three field trips were made in 2010 to collect
      vascular plants, mosses, and lichens, as well as data on their distribution
      within the island. We collected and identified 25 species of lichens, two species
      of vascular plants and one moss. Lichens were the most diverse group found,
      including records of four new genera (Endocarpon, Fuscidea, Lecanographa and
      Verrucaria) and 13 new species for Colombia. The high lichen richness on Malpelo
      might be explained by their efficient form of asexual reproduction (soredia and
      isidia), that may have facilitated their transport to the island by migrating
      birds or wind. Once on the island, it is possible that lichens persist by being
      chemically protected against herbivores. The great number of new generic and
      species records for Colombia is explained by the low number of studies in
      saxicolous lichens conducted so far in the country, particularly on coastal areas
      and remote islands. Only two species of vascular plants were collected, a grass,
      Paspalum sp., and a fern, Pityrogramma calomelanos, and both of them correspond
      to new determinations for Malpelo. A moss species previously reported but with no
      positive identification was collected and identified as Octoblepharum albidum.
      Other species previously reported, for example, some species of shrubs, were not
      observed. The low number of vascular plants is probably due to a combination of
      soil conditions and herbivory by land crabs. This study is the first complete
      inventory of the flora of Malpelo and is a starting and reference point for
      future comparisons among islands in the Eastern

PMID- 24912363
TI  - Antioxidant capacity and fatty acid composition of different parts of Adenocarpus
      complicatus (Fabaceae) from Turkey.
AB  - Adenocarpus complicatus is distributed throughout the Anatolian peninsula and is
      widely used for human and animal nutrition. The purpose of this work was to study
      the antioxidant properties and fatty acid composition of different parts of this
      plant (fruits and mixed materials). The species was collected from Golyuzu
      village of the Seydisehir district near Konya province, Turkey. Fruit and mixed
      parts obtained from this species were ground and a 15g sample was used to prepare
      methanolic extracts. Powdered plant samples were extracted with 100mL methanol in
      a mechanical shaker. The obtained extracts were filtered and concentrated to
      dryness under reduced pressure and were subsequently stored at -20 degrees C.
      Antioxidant components, namely total phenolic and flavonoid content, were
      detected for each extract using spectrophotometric methods. Antioxidant capacity
      was evaluated by various assays including phosphomolybdenum, DPPH free radical
      scavenging capacity, metal chelating activity, and ferric and cupric ion reducing
      power. The fatty acid profiles of plant parts were also determined by using gas
      chromatography. The total phenolic content of fruit (36.21mgGAE/g) was higher
      than that of mixed materials (13.79mgGAE/g). The methanolic extract of mixed
      material had higher amounts of flavonoid than fruit extract. The free radical
      scavenging activity of extracts was expressed as IC50 value (microg/mL) (amount
      required to inhibit DPPH radical formation by 50%). The lower IC50 value reflects
      better free radical scavenging action. The radical scavenging activity of the
      samples was compared with BHT, it showed the mixed material to be almost two
      times more potent than the fruit extract. However, BHT is an excellent free
      radical scavenger with an IC50 of 34.061 microg/mL. The ferric and cupric
      reducing power potentials of the extracts were expressed as EC50 value (the
      effective concentration at which the absorbance was 0.5). Fruit extract exhibited
      strong ferric reducing power with an EC50 of 871.25 microg/mL. The metal
      chelating activity of the extracts increased with concentration. Chelating effect
      was 83.60% for fruit extract at 1mg/mL concentration. Oil content of fruit and
      mixed parts were detected as 6.71 and 6.14%, respectively. A total of 32 fatty
      acids were found in the oil. Essential fatty acids (linoleic and a-linolenic
      acid) were identified as the most abundant fatty acids in the oil. These results
      demonstrated that this plant species can be considered as an alternative to
      synthetic antioxidants. Likewise, the oil obtained from the plant can be used as
      a source of essential fatty acids for food and pharmacological applications.

PMID- 24912364
TI  - Logging impacts on forest structure and seedling dynamics in a Prioria copaifera
      (Fabaceae) dominated tropical rain forest (Talamanca, Costa Rica).
AB  - The factors that determine the existence of tropical forests dominated by a
      single species (monodominated forests) have been the subject of debate for a long
      time. It has been hypothesized that the low frequency of disturbances in
      monodominated forests and the tolerance to shade of the monodominant species are
      two important factors explaining the prolonged dominance of a single species. We
      determined the role of these two factors by examining the effects of logging
      activities on the floristic composition and seedling dynamics in a Prioria
      copaifera dominated forest in Southeastern Costa Rica. We determined the
      floristic composition for trees > or = 2.5cm DBH and the associated recruitment,
      survival and mortality of tree canopy seedlings in two sites logged two (L-02)
      and 12 years (L-12) prior to sampling and an unlogged forest (ULF). Our results
      showed that L-02 stands had lower species richness (25 species) than the L-12 and
      ULF stands (49 and 46 species, respectively). As expected, we found significant
      logging effects on the canopy structure of the altered forests, particularly when
      comparing the L-02 and the ULF stands. Seedling density was higher in ULF (0.96
      seedlings/ m2) than in the L-02 and L-12 stands (0.322 and 0.466 seedlings/m2,
      respectively). However, seedling mortality was higher in the ULF stands (54%)
      than in the L-02 (26%) and L-12 (15%) stands. P. macroloba in L-02 was the only
      species with abundant regeneration under P. copaifera in L-02 stand, where it
      accounted for 35% of the seedlings. Despite the reduction in seedling abundance
      observed after logging, P. copaifera seems to maintain large seedling populations
      in these forests, suggesting that this species maintains its dominance after
      logging disturbances. Our findings challenge the hypothesis that the regeneration
      of monodominant species is not likely to occur under heavily disturbed canopy
      conditions.

PMID- 24912365
TI  - Forest biomass variation in Southernmost Brazil: the impact of Araucaria trees.
AB  - A variety of environmental and biotic factors determine vegetation growth and
      affect plant biomass accumulation. From temperature to species composition,
      aboveground biomass storage in forest ecosystems is influenced by a number of
      variables and usually presents a high spatial variability. With this focus, the
      aim of the study was to evaluate the variables affecting live aboveground forest
      biomass (AGB) in Subtropical Moist Forests of Southern Brazil, and to analyze the
      spatial distribution of biomass estimates. Data from a forest inventory performed
      in the State of Rio Grande do Sul, Southern Brazil, was used in the present
      study. Thirty-eight 1-ha plots were sampled and all trees with DBH > or = 9.5cm
      were included for biomass estimation. Values for aboveground biomass were
      obtained using published allometric equations. Environmental and biotic variables
      (elevation, rainfall, temperature, soils, stem density and species diversity)
      were obtained from the literature or calculated from the dataset. For the total
      dataset, mean AGB was 195.2 Mg/ha. Estimates differed between Broadleaf and Mixed
      Coniferous-Broadleaf forests: mean AGB was lower in Broadleaf Forests
      (AGB(BF)=118.9 Mg/ha) when compared to Mixed Forests (AGB(MF)=250.3 Mg/ha). There
      was a high spatial and local variability in our dataset, even within forest
      types. This condition is normal in tropical forests and is usually attributed to
      the presence of large trees. The explanatory multiple regressions were influenced
      mainly by elevation and explained 50.7% of the variation in AGB. Stem density,
      diversity and organic matter also influenced biomass variation. The results from
      our study showed a positive relationship between aboveground biomass and
      elevation. Therefore, higher values of AGB are located at higher elevations and
      subjected to cooler temperatures and wetter climate. There seems to be an
      important contribution of the coniferous species Araucaria angustifolia in Mixed
      Forest plots, as it presented significantly higher biomass than angiosperm
      species. In Brazil, this endangered species is part of a high diversity forest
      (Araucaria Forest) and has the potential for biomass storage. The results of the
      present study show the spatial and local variability in aboveground biomass in
      subtropical forests and highlight the importance of these ecosystems in global
      carbon stock, stimulating the improvement of future biomass estimates.

PMID- 24912366
TI  - [Distribution patterns of canopy and understory tree species at local scale in a
      Tierra Firme forest, the Colombian Amazonia].
AB  - The effect of environmental variation on the structure of tree communities in
      tropical forests is still under debate. There is evidence that in landscapes like
      Tierra Firme forest, where the environmental gradient decreases at a local level,
      the effect of soil on the distribution patterns of plant species is minimal,
      happens to be random or is due to biological processes. In contrast, in studies
      with different kinds of plants from tropical forests, a greater effect on
      floristic composition of varying soil and topography has been reported. To assess
      this, the current study was carried out in a permanent plot of ten hectares in
      the Amacayacu National Park, Colombian Amazonia. To run the analysis, floristic
      and environmental variations were obtained according to tree species abundance
      categories and growth forms. In order to quantify the role played by both
      environmental filtering and dispersal limitation, the variation of the spatial
      configuration was included. We used Detrended Correspondence Analysis and
      Canonical Correspondence Analysis, followed by a variation partitioning, to
      analyze the species distribution patterns. The spatial template was evaluated
      using the Principal Coordinates of Neighbor Matrix method. We recorded 14 074
      individuals from 1 053 species and 80 families. The most abundant families were
      Myristicaceae, Moraceae, Meliaceae, Arecaceae and Lecythidaceae, coinciding with
      other studies from Northwest Amazonia. Beta diversity was relatively low within
      the plot. Soils were very poor, had high aluminum concentration and were
      predominantly clayey. The floristic differences explained along the ten hectares
      plot were mainly associated to biological processes, such as dispersal
      limitation. The largest proportion of community variation in our dataset was
      unexplained by either environmental or spatial data. In conclusion, these results
      support random processes as the major drivers of the spatial variation of tree
      species at a local scale on Tierra Firme forests of Amacayacu National Park, and
      suggest reserve's size as a key element to ensure the conservation of plant
      diversity at both regional and local levels.

PMID- 24912367
TI  - [Soil-vegetation relationships in a toposequence of the Guayana Shield,
      Venezuela].
AB  - The Guayana Shield is one of the oldest territories in the planet and has
      millions of years subjected to leaching and erosion processes that produce
      oligotrophic soils. This scarcity of nutrients has not avoided the development of
      high, diverse and magnificent forests, where plants have adaptations to survive
      these difficult conditions. The aim of this work was to characterize the physical
      and chemical parameters of the soils in different forest communities of the
      Imataca Forest Reserve (IFR), to establish some interpretations on their origin,
      and some relationships between the edaphic components and the inhabitant species.
      Terrestrial journeys were carried out and two pathways were traced for the
      interpretation of forest communities. In each community, three plots (100m x
      100m) for the ecological survey were established. In each plot, all trees, palms,
      and lianas were measured (dbh> or =10cm; dbh: diameter at breast height); four
      10m x 10m understory sub-plots were evaluated, and a census of all the
      spermatophyta species (dbh< 10cm) was made. Soils were evaluated by means of a
      trial pit in each community, and a bore in each one understory sub-plot. The
      obtained data were analyzed by both a detrended and a canonical correspondence
      analysis. Results from a total of 15 plots allowed us to identify three
      communities: a forest dominated by Mora excelsa located in a narrow valley with
      high content of silt; a swamp forest dominated by Catostemma commune in a sandy
      broad valley, and a forest in clay hills dominated by Alexa imperatricis. Most of
      the soils had a pH between 3.1 and 4.5. Nutrients were in very low concentrations
      (N: 0-0.2%; P: 0-14ppm; K: 0-0.3 Cmol/kg) and A1 in toxicity quantities. We
      observed that Ca/A1 relationship greater than 1 meant a neutralization of the
      toxic effect of Al. Besides, basal area ranged from 20.4 to 32.3m2/ha; the
      highest level (top local forest development) corresponded with the C. commune
      community with a Ca/A1 value of 2.5. This research found an adequate relationship
      between soil and vegetation, as it was able to identify three communities into
      three distinct soil conditions. Nevertheless, edaphic constraints indicated that
      high forest cover must be maintained as an essential element for the conservation
      of these communities.

PMID- 24912368
TI  - [Molecular techniques for cyanobacteria detection at Riogrande II and La Fe water
      reservoirs, Colombia].
AB  - In lentic water bodies as reservoirs occur eutrophication processes, originated
      mainly from human activities (i.e. agriculture, animal exploitation). This influx
      of nutrients in aquatic ecosystems could promote blooms of potentially toxic
      cyanobacteria. The purpose of this work is to detect the presence of
      cyanobacteria strains in water samples, using molecular techniques to help in
      preventive management of reservoirs dedicated to water purification. We used two
      molecular techniques to detect genes implied with the synthesis of hepatotoxic
      microcystins from potentially toxic cyanobacteria strains, and to evaluate the
      molecular diversity of cyanobacteria in water samples from two high-mountain
      reservoirs used for purification of drinking water for the metropolitan area of
      Medellin, Colombia. Between 2010-2011 collections of 12 water samples were taken
      and DNA extraction together with PCR and DGGE analyses where carried out. We
      amplified 22 sequences between 250-300bp of the genes mcyA and mcyE, and these
      sequences were related with several strains and cyanobacteria genera accessions
      from NCBI-GenBank databases. Moreover, sequence amplifications of the 16S small
      ribosomal RNA subunit - 16S rRNA- between 400-800bp were also performed in order
      to use them for the DGGE technique. The amplification products of DGGE were set
      in polyacrilamide gel with posterior denaturing electrophoresis, and the scanned
      images of the gel bands were analysed with the software GelCompar II. For
      Riogrande II and La Fe reservoirs we found 35 and 30 different DGGE bands,
      respectively, as a measurement of molecular diversity in these artificial
      ecosystems. Here, we demonstrated the utility of two molecular techniques for the
      detection of genes associated with toxicity and molecular diversity of
      cyanobacteria in reservoirs destined for drinking water in urban centers. We
      recommend strongly following with periodically molecular biology studies in these
      ecosystems combined with limnological and ecological data, as new tools for
      management of plants of water purification and for the prevention of potentially
      public health concerns.

PMID- 24912370
TI  - Computerized detection of breast lesions using deformable part models in
      ultrasound images.
AB  - Ultrasound imaging is considered an important complementary technique for the
      screening of dense breasts. Detection of lesions at an early stage is a key step
      in which computerized lesion detection systems could play an important role in
      the analysis of US images. In this article, we propose adaptation of a generic
      object detection technique, deformable part models, to detect lesions in breast
      US images. The data set used in this study included 326 images, all from
      different patients (54 malignant lesions, 109 benign lesions and 163 healthy
      breasts). In terms of lesion detection, our proposal outperformed some of the
      most relevant approaches described in the literature; we obtained a sensitivity
      of 86% with 0.28 false-positive detection per image and an Az value of 0.975. In
      the detection of malignant lesions, our proposed approached had an Az value of
      0.93 and a sensitivity of 78% at a 1.15 false-positive detections per image. 

PMID- 24912369
TI  - Internalization of isolated functional mitochondria: involvement of
      macropinocytosis.
AB  - In eukaryotic cells, mitochondrial dysfunction is associated with a variety of
      human diseases. Delivery of exogenous functional mitochondria into damaged cells
      has been proposed as a mechanism of cell transplant and physiological repair for
      damaged tissue. We here demonstrated that isolated mitochondria can be
      transferred into homogeneic and xenogeneic cells by simple co-incubation using
      genetically labelled mitochondria, and elucidated the mechanism and the effect of
      direct mitochondrial transfer. Intracellular localization of exogenous
      mitochondria was confirmed by PCR, real-time PCR, live fluorescence imaging,
      three-dimensional reconstruction imaging, continuous time-lapse microscopic
      observation, flow cytometric analysis and immunoelectron microscopy. Isolated
      homogeneic mitochondria were transferred into human uterine endometrial gland
      derived mesenchymal cells in a dose-dependent manner. Moreover, mitochondrial
      transfer rescued the mitochondrial respiratory function and improved the cellular
      viability in mitochondrial DNA-depleted cells and these effects lasted several
      days. Finally, we discovered that mitochondrial internalization involves
      macropinocytosis. In conclusion, these data support direct transfer of exogenous
      mitochondria as a promising approach for the treatment of various diseases. 

PMID- 24912371
TI  - Quantitative analysis of four types of primary glomeropathy by application of a
      decision forest to ultrasonic and laboratory characteristics.
AB  - The aim of this study was to apply a decision forest to analysis of the
      ultrasound characteristics and laboratory test indices of four types of primary
      glomerulopathy, and quantitative analysis of the four pathologic types using a
      combination of these two methods. The decision trees were derived from 41
      clinical indices and 5 characteristic sonographic indices obtained for the left
      kidney. Fifty-six patients who had undergone ultrasound-guided renal biopsy were
      reviewed retrospectively, and on pathologic examination, the patients were
      diagnosed with primary glomerulopathy, which includes mesangial proliferative
      glomerulonephritis, membranous nephropathy, immunoglobulin A nephropathy and
      minimal change disease. In this study, eight characteristic indicators were
      correlated with pathologic type in the 56 cases of primary glomerulopathy. The
      order calculated by decision forests, from high to low, is proteinuria, length of
      kidney, serum creatinine, plasma albumin, area of kidney, total protein,
      thickness of renal parenchyma, 24-h urine protein. The glomerulopathy with the
      highest ++++ proteinuria is membranous nephropathy, which accounts for 39.2%
      (22/56) of the total sample; this was followed by minimal change disease,
      mesangial proliferative glomerulonephritis and immunoglobulin A nephropathy. On
      the basis of our analysis of 41 clinical indices, the key indices for
      quantitative analysis of primary glomerulonephritis are laboratory tests, and
      these include urine protein, serum creatinine, plasma albumin, total serum
      protein and 24-h urine protein. The three key sonographic features are
      measurement indices: renal length, renal area and renal parenchymal thickness.
      From the eight characteristic indicators, we observed that with respect to
      severity (from most severe to least severe), the four types of glomerulopathy are
      membranous nephropathy, minimal change disease, mesangial proliferative
      glomerulonephritis and immunoglobulin A nephropathy.

PMID- 24912373
TI  - A closed-form differential formulation for ultrasound spatial calibration: multi
      wedge phantom.
AB  - Calibration is essential in freehand 3-D ultrasound to find the spatial
      transformation from the image coordinates to the sensor coordinate system.
      Calibration accuracy has significant impact on image-guided interventions. We
      introduce a new mathematical framework that uses differential measurements to
      achieve high calibration accuracy. Accurate measurements of axial differences in
      ultrasound images of a multi-wedge phantom are used to calculate the calibration
      matrix with a closed-form solution. The multi-wedge phantom has been designed
      based on the proposed differential framework and can be mass-produced
      inexpensively using a 3-D printer. The proposed method enables easy, fast and
      highly accurate ultrasound calibration, which is essential for most current
      ultrasound-guided applications and also widens the range of new applications. The
      precision of the method using only a single image of the phantom is comparable to
      that of the standard N-wire method using 50 images. The method can also directly
      take advantage of the fine sampling rate of radiofrequency ultrasound data to
      achieve very high calibration accuracy. With 100 radiofrequency ultrasound
      images, the method achieves a point reconstruction error of 0.09 +/- 0.39 mm.

PMID- 24912372
TI  - Evaluation of muscle quality reliability and racial differences in body
      composition of overweight individuals.
AB  - The purpose of this study was to evaluate the reliability of ultrasound measures
      of muscle cross-sectional area (mCSA) and echo intensity (EI) in overweight
      subjects. A secondary purpose was to evaluate racial differences in EI, mCSA and
      body composition. In 33 overweight subjects, mCSA and EI were determined from a
      panoramic ultrasound scan of the vastus lateralis. Body composition was
      determined using dual-energy X-ray absorptiometry (DXA). Reliability of mCSA and
      EI was calculated from the intra-class correlation coefficient (ICC), standard
      error of the measurement (SEM) and minimal difference (MD). The ICC, SEM and MD
      for mCSA and EI were 0.87, 2.12, 5.89 and 0.74, 4.58, 12.69, respectively. There
      were no significant racial differences in body composition (p > 0.05); however,
      EI was significantly lower for black subjects (p = 0.018). These results suggest
      ultrasound measures of mCSA and EI are reliable in overweight subjects, and EI
      may provide additional muscle composition evaluations, beyond DXA measures.

PMID- 24912374
TI  - Quantification of myocardial fibrosis by digital image analysis and interactive
      stereology.
AB  - BACKGROUND: Cardiac fibrosis disrupts the normal myocardial structure and has a
      direct impact on heart function and survival. Despite already available digital
      methods, the pathologist's visual score is still widely considered as ground
      truth and used as a primary method in histomorphometric evaluations. The aim of
      this study was to compare the accuracy of digital image analysis tools and the
      pathologist's visual scoring for evaluating fibrosis in human myocardial
      biopsies, based on reference data obtained by point counting performed on the
      same images. METHODS: Endomyocardial biopsy material from 38 patients diagnosed
      with inflammatory dilated cardiomyopathy was used. The extent of total cardiac
      fibrosis was assessed by image analysis on Masson's trichrome-stained tissue
      specimens using automated Colocalization and Genie software, by Stereology grid
      count and manually by Pathologist's visual score. RESULTS: A total of 116 slides
      were analyzed. The mean results obtained by the Colocalization software (13.72 +/
      12.24%) were closest to the reference value of stereology (RVS), while the Genie
      software and Pathologist score gave a slight underestimation. RVS values
      correlated strongly with values obtained using the Colocalization and Genie
      (r>0.9, p<0.001) software as well as the pathologist visual score. Differences in
      fibrosis quantification by Colocalization and RVS were statistically
      insignificant. However, significant bias was found in the results obtained by
      using Genie versus RVS and pathologist score versus RVS with mean difference
      values of: -1.61% and 2.24%. Bland-Altman plots showed a bidirectional bias
      dependent on the magnitude of the measurement: Colocalization software
      overestimated the area fraction of fibrosis in the lower end, and underestimated
      in the higher end of the RVS values. Meanwhile, Genie software as well as the
      pathologist score showed more uniform results throughout the values, with a
      slight underestimation in the mid-range for both. CONCLUSION: Both applied
      digital image analysis methods revealed almost perfect correlation with the
      criterion standard obtained by stereology grid count and, in terms of accuracy,
      outperformed the pathologist's visual score. Genie algorithm proved to be the
      method of choice with the only drawback of a slight underestimation bias, which
      is considered acceptable for both clinical and research evaluations. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/9857909611227193.

PMID- 24912375
TI  - Chronic Schistosoma mekongi in a traveler--a case report and review of the
      literature.
AB  - Travel-related schistosomiasis can be detected in patients without symptoms of
      acute or chronic infection. A case of Schistosoma mekongi acquired in an endemic
      area of Laos and discovered unexpectedly from colon biopsies taken 5 years after
      infection is presented here. A literature review of previous cases of S. mekongi
      infection specifically associated with travelers is then presented.

PMID- 24912376
TI  - Dementia, walking outdoors and getting lost: incidence, risk factors and
      consequences from dementia-related police missing-person reports.
AB  - OBJECTIVES: To estimate incidence, identify consequences and potential risk
      factors for harm in people with dementia who got lost in one UK policing region.
      METHODS: In a retrospective observational study, data were extracted from missing
      person records over a four-year period in one UK policing region (population of
      2.1 million). RESULTS: Two hundred and eighty-one incidents of getting lost were
      identified. Incidence of getting lost was estimated at 0.5% of the regional
      dementia population. Fifty-nine percent of reports came from domestic settings,
      29% from care homes/hospitals, and 12% on excursions from home. Five percent (n =
      15) sustained significant harm, including two deaths. Average age was 78 years
      (SD 8.3). Harm was associated with older age (mean difference 6.16 years, CI 1.86
      to 10.46, p = 0.005, t = 2.82), length of time missing (Mdn time 2.48 hours; IQR
      0.97 to 9.45, p = 0.02), and season (9% winter, 2% summer, p = 0.006). The length
      of time missing increased with delays in reporting to police (r = 0.15, p =
      0.018), getting lost at night (Mdn time 1.70 hours, IQR 0.52-3.32, p = 0.028),
      driving themselves (Mdn time 2.45 hours, IQR 0.42-2.00, p = 0.001), and using
      public transport (Mdn 1.78 hours, IQR 1.07-3.92, p = 0.001). CONCLUSION:
      Incidence in this study suggests getting lost is a low-frequency event for people
      with dementia but for a small minority, the risks are considerable. Exploratory
      analyses suggest individual and environmental factors increase the risk of harm.
      Suitable methods need to be developed to replicate these findings in larger
      prospective samples. A focus on the predictors of harm may aid development of
      assessment protocols to ensure intervention is proportionate.

PMID- 24912377
TI  - Services and supports for young children with Down syndrome: parent and provider
      perspectives.
AB  - BACKGROUND: As individuals with Down syndrome are living longer and more socially
      connected lives, early access to supports and services for their parents will
      ensure an optimal start and improved outcomes. The family's journey begins at the
      child's diagnosis, and cumulative experiences throughout infancy and childhood
      set the tone for a lifetime of decisions made by the family regarding services,
      supports and activities. METHODS: This study utilized focus groups and interviews
      with seven nurses, five therapists, 25 service co-ordinators, and 10 English- and
      three Spanish-speaking parents to better understand family experiences and
      perceptions on accessing Down syndrome-related perinatal, infant and childhood
      services and supports. RESULTS: Parents and providers reflected on key early life
      issues for children with Down syndrome and their families in five areas: prenatal
      diagnosis; perinatal care; medical and developmental services; care co-ordination
      and services; and social and community support. CONCLUSIONS: Systems of care are
      not consistently prepared to provide appropriate family-centred services to
      individuals with Down syndrome and their families. Individuals with disabilities
      require formal and informal supports from birth to achieve and maintain a high
      quality of life.

PMID- 24912379
TI  - Mesozoic lacewings from China provide phylogenetic insight into evolution of the
      Kalligrammatidae (Neuroptera).
AB  - BACKGROUND: The Kalligrammatidae are distinctive, large, conspicuous, lacewings
      found in Eurasia from the Middle Jurassic to mid Early Cretaceous. Because of
      incomplete and often inadequate fossil preservation, an absence of detailed
      morphology, unclear relationships, and unknown evolutionary trends, the
      Kalligrammatidae are poorly understood. RESULTS: We describe three new
      subfamilies, four new genera, twelve new species and four unassigned species from
      the late Middle Jurassic Jiulongshan and mid Early Cretaceous Yixian Formations
      of China. These kalligrammatid taxa exhibit diverse morphological characters,
      such as mandibulate mouthparts in one major clade and siphonate mouthparts in the
      remaining four major clades, the presence or absence of a variety of distinctive
      wing markings such as stripes, wing spots and eyespots, as well as multiple major
      wing shapes. Based on phylogenetic analyses, the Kalligrammatidae are divided
      into five principal clades: Kalligrammatinae Handlirsch, 1906, Kallihemerobiinae
      Ren & Engel, 2008, Meioneurinae subfam. nov., Oregrammatinae subfam. nov. and
      Sophogrammatinae subfam. nov., each of which is accorded subfamily-level status.
      Our results show significant morphological and evolutionary differentiation of
      the Kalligrammatidae family during a 40 million-year-interval of the mid
      Mesozoic. CONCLUSION: A new phylogeny and classification of five subfamilies and
      their constituent genera is proposed for the Kalligrammatidae. These diverse, yet
      highly specialized taxa from northeastern China suggest that eastern Eurasia
      likely was an important diversification center for the Kalligrammatidae.
      Kalligrammatids possess an extraordinary morphological breadth and panoply of
      adaptations during the mid-Mesozoic that highlight our conclusion that their
      evolutionary biology is much more complex than heretofore realized.

PMID- 24912378
TI  - Chronic-disease patients and their use of out-of-hours primary health care: a
      cross-sectional study.
AB  - BACKGROUND: The general practitioner (GP) plays an important role for chronic
      disease care. Continuous and close contact with daytime general practice is
      intended to prevent medical problems arising outside office hours due to already
      diagnosed chronic disease. However, previous studies indicate that patients with
      chronic diseases are frequent users of out-of-hours primary care services (OOH),
      but knowledge is limited on reasons for encounter (RFE), severity of symptoms,
      and OOH patient handling. We aimed to describe contacts to the OOH services from
      patients with chronic heart disease, lung disease, severe psychiatric disorders,
      diabetes, and cancer in terms of RFE, OOH GP diagnosis, assessed severity of
      symptoms, and actions taken by the GP. METHODS: Eligible patients (aged 18 years
      and older) were randomly sampled from a one-year cross-sectional study comprising
      15,229 contacts to the OOH services in the Central Denmark Region. A cohort of
      patients with one or more of the five selected chronic diseases were identified
      by linking data on the Danish civil registration number (CPR) through specific
      nationwide Danish health registers. RESULTS: Out of 13,930 identified unique
      patients, 4,912 had at least one of the five chronic diseases. In total, 25.9% of
      all calls to the OOH services came from this chronic disease patient group due to
      an acute exacerbation; 32.6% of these calls came from patients with psychiatric
      diagnoses. Patients with chronic disease were more likely to receive a face-to
      face contact than the remaining group of patients, except for calls from patients
      with a psychiatric disorder who were more often completed through a telephone
      consultation. Patients with heart disease calling due to a new health problem
      formed the largest proportion of all OOH referrals to hospital (13.3%) compared
      to calls from the other groups with chronic disease (3.4-6.7%). CONCLUSIONS: A
      third of the patients randomly sampled by their OOH call had one or more of the
      five selected chronic diseases (i.e. chronic lung disease, heart disease,
      diabetes, psychiatric disease, or cancer). Patients with chronic disease were
      more often managed by OOH GPs than other patients.

PMID- 24912380
TI  - Optomotor-blind in the development of the Drosophila HS and VS lobula plate
      tangential cells.
AB  - The horizontal system and vertical system cells of the dipteran optic lobes are
      well understood regarding their physiology and role in visually guided behavior.
      Little is known, however, about their development. Drosophila optomotor-blind
      (omb) is required for the development of the HS/VS cells which are lacking in the
      adult brain of the In(1)omb[H31] regulatory mutant. We have analyzed the omb
      regulatory region, required for HS/VS development, for enhancers active in the
      central nervous system. A 1-kb fragment, ombJb, was identified 114 kb downstream
      of the omb transcription start site, that could drive expression in much of the
      presumptive embryonic optic lobe anlage. Expression in these cells is lost in
      In(1)omb[H31] suggesting that they contain the HS/VS precursor cell(s). We used
      Laser ablation in the embryonic CNS in order to localize the position of the
      HS/VS precursor cell(s) in this tissue. An omb-Gal4 enhancer trap line, which
      showed activity in the optic lobe anlage in a pattern similar to ombJb enhancer,
      was used to drive GFP expression, thus allowing to focus the Laser beam to the
      relevant area. We identified a small region in the embryonic brain from which the
      HS/VS cells are likely to develop. Omb encodes a transcription factor of the T
      box family. Since loss of omb disrupts HS/VS cell development, we assume that
      HS/VS ontogeny is controlled by Omb target genes. As a first step toward their
      identification, we characterized the Omb DNA-binding specificity.

PMID- 24912381
TI  - Energy-effective frost-free coatings based on superhydrophobic aligned nanocones.
AB  - We demonstrate the feasibility of superhydrophobic aligned nanocones as energy
      effective frost-free coatings. Exemplified by Co(OH)2 nanocone films with
      condensed microdrop self-removal ability, their edge and whole-surface frosting
      time can be delayed to about 10 and 150 min, respectively. By using a Teflon
      gasket to shield edges, the samples can keep frost-free state over 90 min.
      Further, the lasting frost-free state can be realized by intermittent weak
      airflow heating, which is energy-effective in contrast to usual high-power
      heating for defrosting flat surfaces. These findings are significant to develop
      antifrosting nanotechnologies for energy-effective heat exchangers such as heat
      pumps and refrigerators. 

PMID- 24912383
TI  - Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory
      cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an
      in vivo and in vitro study.
AB  - Global warming is a challenge to animal health, because of increased heat stress,
      with subsequent induction of immunosuppression and increased susceptibility to
      disease. Toll-like receptors (TLR) are pattern recognition receptors that act as
      sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a
      signaling cascade and production of inflammatory cytokines, which eradicate
      pathogens and maintain the health of the host. We hypothesized that the TLR
      signaling pathway plays a role in immunosuppression in heat-stressed pigs. We
      explored the changes in the expression of TLR2, TLR4 and the concentration of
      acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-gamma in Bama
      miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and
      in vivo models. The results showed that heat stress induced the upregulation of
      cortisol in the plasma of pigs (P<0.05); TLR4 mRNA was elevated, but IL-2 was
      reduced in peripheral blood mononuclear cells (PBMC, P<0.05). The white blood
      cell count and the percentage of granulocytes (eosinophilic+basophilic) decreased
      significantly in heat-stressed pigs (P<0.05). In the in vitro model (PBMC heat
      shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression
      also increased, as did the concentration of IL-12 in supernatants. However, IFN
      gamma was significantly reduced in PBMC culture supernatants (P<0.05). We
      concluded that a consecutive heat stress period elevated the expression of TLR2
      and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These
      data indicate that TLR activation and dysregulation of cytokine expression in
      response to prolonged heat stress may be associated with immunosuppression and
      increased susceptibility to antigenic challenge in Bama miniature pigs. 

PMID- 24912382
TI  - Severity of liver disease affects HCV kinetics in patients treated with
      intravenous silibinin monotherapy.
AB  - BACKGROUND: HCV kinetic analysis and modelling during antiviral therapy have not
      been performed in decompensated cirrhotic patients awaiting liver
      transplantation. Here, viral and host parameters were compared in three groups of
      patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days
      according to the severity of their liver disease. METHODS: Data were obtained
      from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with
      decompensated cirrhosis. The standard-biphasic model with time-varying SIL
      effectiveness (from 0 to final effectiveness [epsilonmax]) was fitted to viral
      kinetic data. RESULTS: Baseline viral load and age were significantly associated
      with the severity of liver disease (P<0.0001). A biphasic viral decline was
      observed in most patients with a higher first phase decline in patients with less
      severe liver disease. The epsilonmax was significantly (P<=0.032) associated with
      increasing severity of liver disease (non-cirrhotic epsilonmax [se]=0.86 [0.05],
      compensated cirrhotic epsilonmax=0.69 [0.06] and decompensated cirrhotic
      epsilonmax=0.59 [0.1]). The second phase decline slope was not significantly
      different among groups (mean 1.88 +/-0.15 log10 IU/ml/week, P=0.75) as was the
      rate of change of SIL effectiveness (k=2.12/day [se=0.18/day]). HCV-infected cell
      loss rate (delta [se]=0.62/day [0.05/day]) was high and similar among groups.
      CONCLUSIONS: The high loss rate of HCV-infected cells suggests that sufficient
      dose and duration of SIL might achieve viral suppression in advanced liver
      disease.

PMID- 24912384
TI  - Functional brain imaging in gastroenterology: to new beginnings.
AB  - With more than 100 studies published over the past two decades, functional brain
      imaging research in gastroenterology has become an established field; one that
      has enabled improved insight into the supraspinal responses evoked by
      gastrointestinal stimulation both in health and disease. However, there remains
      considerable inter-study variation in the published results, largely owing to
      methodological differences in stimulation and recording techniques, heterogeneous
      patient selection, lack of control for psychological factors and so on. These
      issues with reproducibility, although not unique to studies of the
      gastrointestinal tract, can lead to unjustified inferences. To obtain consistent
      and more clinically relevant results, there is a need to optimize and standardize
      brain imaging studies across different centres. In addition, the use of
      complementary and more novel brain imaging modalities and analyses, which are now
      being used in other fields of research, might help unravel the factors at play in
      functional gastrointestinal disorders. This Review highlights the areas in which
      functional brain imaging has been useful and what it has revealed, the areas that
      are in need of improvement, and finally suggestions for future directions. 

PMID- 24912386
TI  - Expert consensus document. The International Scientific Association for
      Probiotics and Prebiotics consensus statement on the scope and appropriate use of
      the term probiotic.
AB  - An expert panel was convened in October 2013 by the International Scientific
      Association for Probiotics and Prebiotics (ISAPP) to discuss the field of
      probiotics. It is now 13 years since the definition of probiotics and 12 years
      after guidelines were published for regulators, scientists and industry by the
      Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO).
      The FAO/WHO definition of a probiotic--"live microorganisms which when
      administered in adequate amounts confer a health benefit on the host"--was
      reinforced as relevant and sufficiently accommodating for current and anticipated
      applications. However, inconsistencies between the FAO/WHO Expert Consultation
      Report and the FAO/WHO Guidelines were clarified to take into account advances in
      science and applications. A more precise use of the term 'probiotic' will be
      useful to guide clinicians and consumers in differentiating the diverse products
      on the market. This document represents the conclusions of the ISAPP consensus
      meeting on the appropriate use and scope of the term probiotic.

PMID- 24912388
TI  - GERD: body position affects infant GER but not symptoms.
AB  - Increased gastro-oesophageal reflux (GER) is described as a very common problem
      in infants. Loots et al. investigated the effect of the left lateral position on
      reflux and symptoms, finding that body position affects GER but not symptoms. The
      data highlight the difficulties faced in investigating reflux disease in the
      paediatric population.

PMID- 24912389
TI  - The role of glycosylation in IBD.
AB  - A number of genetic and immunological studies give impetus for investigating the
      role of glycosylation in IBD. Experimental mouse models have helped to delineate
      the role of glycosylation in intestinal mucins and to explore the putative
      pathogenic role of glycosylation in colitis. These experiments have been extended
      to human studies investigating the glycosylation patterns of intestinal mucins as
      well as levels of glycans of serum glycoproteins and expression of glycan
      receptors. These early human studies have generated interesting hypotheses
      regarding the pathogenic role of glycans in IBD, but have generally been
      restricted to fairly small underpowered studies. Decreased glycosylation has been
      observed in the intestinal mucus of patients with IBD, suggesting that a
      defective inner mucus layer might lead to increased bacterial contact with the
      epithelium, potentially triggering inflammation. In sera, decreased
      galactosylation of IgG has been suggested as a diagnostic marker for IBD.
      Advances in glycoprofiling technology make it technically feasible and affordable
      to perform high-throughput glycan pattern analyses and to build on previous work
      investigating a much wider range of glycan parameters in large numbers of
      patients. 

PMID- 24912390
TI  - Treatment options for chronic pancreatitis.
AB  - This Review covers the latest developments in the treatment options for chronic
      pancreatitis. Pain is the most frequent and dominant symptom in patients with
      chronic pancreatitis, which ranges from severe disabling continuous pain to mild
      pain attacks and pain-free periods. Conventional treatment strategies and recent
      changes in the treatment of pain in patients with chronic pancreatitis are
      outlined. The different treatment options for pain consist of medical therapy,
      endoscopy or surgery. Their related merits and drawbacks are discussed. Finally,
      novel insights in the field of genetics and microbiota are summarized, and future
      perspectives are discussed. 

PMID- 24912392
TI  - Pancreatic cancer: surprising role for fibrosis.

PMID- 24912394
TI  - Treatment persistence and switching in triptan users: a systematic literature
      review.
AB  - OBJECTIVE: To conduct a systematic review to evaluate persistence to and
      switching of triptan therapy for the acute treatment of migraine. BACKGROUND:
      Migraine affects over 12% of adults in Western countries and an estimated 36
      million people in the United States. Triptans are an abortive treatment option in
      patients with moderate to severe migraine. Despite the safety and efficacy of
      triptans reported in clinical trials, observational studies have consistently
      demonstrated low persistence to therapy and frequent switching among products
      over time. METHODS: The following databases were researched: Medline, CENTRAL,
      and EMBASE. Detailed inclusion and exclusion criteria were specified a priori
      before conducting abstract and full-text screening. Included studies were
      required to: (1) report triptan use for migraine treatment; (2) report measures
      of persistence and/or switching patterns; (3) study migraineurs aged 18 years or
      older; and (4) conduct an observational study. Studies were excluded if they (1)
      incorporated interventional study design; (2) lack information or relevance to
      outcome of interest; (3) were not original research; (4) did not clearly state
      the results; and (5) were not written in English. Abstracts and full-text
      articles were reviewed independently by two investigators. RESULTS: Out of 595
      studies identified, 380 studies were included for abstract screening. A total of
      12 articles met the eligibility criteria after full-text screening of 44 studies,
      including four studies from reference search. The proportion of patients that
      remained persistent up to six refills of an index triptan ranged from 3.2% to
      12.6% and the proportion of patients that never refilled their index triptan
      ranged from 38% to 65.8%. In addition to those patients who discontinued, several
      studies reported that 5-9% of newly initiating triptan users switch to a
      different triptan before refilling their original medication. Finally, several
      studies reported the 1-year probability of discontinuation among a general group
      of triptan users (not limited to treatment naive patients) to be between 30% and
      60%. CONCLUSIONS: Triptans can be a valuable option for acute treatment of
      migraine. However, studies have shown that treatment persistence is low. This,
      along with frequent switching behaviors, suggests that a significant unmet
      clinical need remains despite the wide availability of triptans.

PMID- 24912395
TI  - Reductive activation and structural rearrangement in superoxide reductase: a
      combined infrared spectroscopic and computational study.
AB  - Superoxide reductases (SOR) are a family of non-heme iron enzymes that limit
      oxidative stress by catalysing the reduction of superoxide to hydrogen peroxide
      and, thus, represent model systems for the detoxification of reactive oxygen
      species. In several enzymes of this type, reductive activation of the active site
      involves the reversible dissociation of a glutamate from the proposed substrate
      binding site at the iron. In this study we have employed IR spectroscopic and
      theoretical methods to gain insights into redox-linked structural changes of 1Fe
      type superoxide reductases, focusing on the enzyme from the archaeon Ignicoccus
      hospitalis. Guided by crystal structure data and complemented by spectra
      calculation for an active site model, the main IR difference signals could be
      assigned. These signals reflect redox-induced structural changes in the first
      coordination sphere of the iron centre, adjacent loop and helical regions, and
      more remote beta-sheets. By comparison with the spectra obtained for the E23A
      mutant of Ignicoccus hospitalis SOR, it is shown that glutamate E23 dissociates
      reversibly from the ferrous iron during reductive activation of the wild type
      enzyme. Moreover, this process is found to trigger a global conformational
      transition of the protein that is strictly dependent on the presence of E23.
      Similar concerted structural changes can be inferred from the IR spectra of
      related SORs such as that from Archaeoglobus fulgidus, indicating a widespread
      mechanism. A possible functional role of this process in terms of synergistic
      effects during reductive activation of the homotetrameric enzyme is proposed. 

PMID- 24912398
TI  - The impact of supportive counselling on women's psychological wellbeing after
      miscarriage--a randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of supportive counselling after
      miscarriage. DESIGN: Randomised controlled trial. SETTING: University hospital.
      SAMPLE: Two hundred and eighty women with miscarriage. METHOD: Women were
      randomised to receive supportive counselling from a nurse (at diagnosis and 2
      weeks later) or routine care. Psychological wellbeing was measured with the
      General Health Questionnaire (GHQ-12) and Beck Depression Inventory (BDI). MAIN
      OUTCOME MEASURES: Primary outcome measured the proportion of women suffering
      psychological distress (GHQ-12 score >=4) at 3 months after miscarriage.
      Secondary outcomes were GHQ-12 and BDI scores at 6 weeks, 3 and 6 months.
      RESULTS: There was no difference in the proportion of women suffering
      psychological distress at 3 months after miscarriage (17.1% in counselling group
      versus 24.4% in control group; 95% CI -0.034 to 0.177; P = 0.19). However, for
      the subgroup of women (n = 152) with high baseline GHQ-12 scores, the median GHQ
      12 score in the counselling group was significantly lower than the control group
      at 6 weeks (median score 3 versus 4.5 in counselling and control groups; P =
      0.04) and 3 months (median score 1 versus 2.5 in counselling and control groups;
      P = 0.03). Similarly, for women with high baseline BDI scores (BDI > 12), the
      proportion for women continuing to score high was significantly lower in the
      counselling group 6 weeks after miscarriage (33.3 versus 61.1% in counselling
      group and control group; P = 0.03). CONCLUSIONS: Although the results of current
      study do not justify routine counselling of all women following miscarriage, a
      supportive counselling programme for selected women with high levels of
      psychological distress is promising and merits further investigation.

PMID- 24912396
TI  - EZH2: an emerging role in melanoma biology and strategies for targeted therapy.
AB  - Histone modifications are increasingly being recognized as important epigenetic
      mechanisms that govern chromatin structure and gene expression. EZH2 is the
      catalytic subunit of the polycomb repressive complex 2 (PRC2), responsible for
      tri-methylation of lysine 27 on histone 3 (H3K27me3) that leads to gene
      silencing. This highly conserved histone methyltransferase is found to be
      overexpressed in many different types of cancers including melanoma, where it is
      postulated to abnormally repress tumor suppressor genes. Somatic mutations have
      been identified in approximately 3% of melanomas, and activating mutations
      described within the catalytic SET domain of EZH2 confer its oncogenic activity.
      In the following review, we discuss the evidence that EZH2 is an important driver
      of melanoma progression and we summarize the progress of EZH2 inhibitors against
      this promising therapeutic target. 

PMID- 24912399
TI  - Clinical comparison of metal ceramic resin-bonded fixed dental prostheses with a
      conventional and a mixed retainer design.
AB  - STATEMENT OF PROBLEM: Little is known about the clinical performance of fixed
      dental prostheses that rigidly connect adhesive retainers and crowns. PURPOSE:
      The purpose of this retrospective analysis was to assess and compare the clinical
      performance of resin-bonded fixed dental prostheses with a conventional and a
      mixed retainer design. MATERIAL AND METHODS: Included as participants were all
      patients of the hospital since 2004 with regular clinical follow-up who were
      treated with 3-unit or 4-unit metal ceramic resin-bonded fixed dental prostheses
      with a conventional 2-adhesive retainer design (conventional group) or with a
      mixed type combining an adhesive retainer with a crown or a partial crown
      retainer (mixed group). The analysis included 84 participants with a total of 57
      (64%) prostheses in the conventional group and 32 (36%) prostheses in the mixed
      group. Treatment and data collection were standardized. Cumulative survival
      without failure (defined as a restoration in need of replacement), chipping, and
      debonding were estimated by the Kaplan-Meier method and compared for the groups
      (log-rank test) (alpha=.05). RESULTS: During a mean observation period of 4.1
      years (SD, 2.5 years; minimum, 0.4 years; maximum, 9.4 years), 12 complications
      occurred in 10 restorations. Defects of the ceramic veneer (n=6) were observed
      most frequently. The estimated 5-year failure-free survival rate was 97.4%
      (standard error, .025) in the conventional group and 95% (standard error, .049)
      in the mixed group (log-rank, P=.32). The 5-year cumulative survival rate without
      chipping was 90.7% (standard error, .064) for the conventional group and 93.8%
      (standard error, .061) for the mixed group (log-rank, P=.44). The 5-year
      cumulative survival rate without debonding was 95.1% (standard error, .034) for
      the conventional group and 91.5% (standard error, .058) for the mixed group (log
      rank, P=.54). CONCLUSIONS: Limited by a small sample size and a short follow-up
      period, the findings of this retrospective analysis indicate that the clinical
      performance, in terms of survival and the incidence of complications, is
      comparable for conventional resin-bonded fixed dental prostheses and those that
      rigidly connect an adhesive wing and a partial or complete crown. Acceptable 5
      year survival and complication rates imply that the medium-term prognosis for
      resin-bonded restorations with a retentive preparation design is comparable with
      that for conventional fixed dental prostheses.

PMID- 24912400
TI  - An alternative, arginase-independent pathway for arginine metabolism in
      Kluyveromyces lactis involves guanidinobutyrase as a key enzyme.
AB  - Most available knowledge on fungal arginine metabolism is derived from studies on
      Saccharomyces cerevisiae, in which arginine catabolism is initiated by releasing
      urea via the arginase reaction. Orthologues of the S. cerevisiae genes encoding
      the first three enzymes in the arginase pathway were cloned from Kluyveromyces
      lactis and shown to functionally complement the corresponding deletion in S.
      cerevisiae. Surprisingly, deletion of the single K. lactis arginase gene KlCAR1
      did not completely abolish growth on arginine as nitrogen source. Growth rate of
      the deletion mutant strongly increased during serial transfer in shake-flask
      cultures. A combination of RNAseq-based transcriptome analysis and (13)C-(15)N
      based flux analysis was used to elucidate the arginase-independent pathway.
      Isotopic (13)C(15)N-enrichment in gamma-aminobutyrate revealed succinate as the
      entry point in the TCA cycle of the alternative pathway. Transcript analysis
      combined with enzyme activity measurements indicated increased expression in the
      Klcar1Delta mutant of a guanidinobutyrase (EC.3.5.3.7), a key enzyme in a new
      pathway for arginine degradation. Expression of the K. lactis KLLA0F27995g
      (renamed KlGBU1) encoding guanidinobutyrase enabled S. cerevisiae to use
      guanidinobutyrate as sole nitrogen source and its deletion in K. lactis almost
      completely abolish growth on this nitrogen source. Phylogenetic analysis suggests
      that this enzyme activity is widespread in fungi.

PMID- 24912401
TI  - Association between living arrangements and depressive symptoms among older women
      and men in South Korea.
AB  - PURPOSE: We investigated the relationship between different types of living
      arrangements and depressive symptoms among older Korean women and men. METHODS:
      Data were obtained from a nationally representative cross-sectional health survey
      conducted in 2009 in South Korea. A total of 60,305 participants (34,172 women
      and 26,133 men) aged 60 years and older were included in the analysis. The living
      arrangements were categorised into six types as follows: (1) living with a spouse
      only; (2) living with a spouse in an extended family; (3) living with a spouse in
      a nuclear family; (4) living alone; (5) living without a spouse in an extended
      family; and (6) living without a spouse in a nuclear family. The Korean version
      of the Center for Epidemiologic Studies Depression Scale was used as the
      measurement tool for depressive symptoms. We used multiple regression analysis to
      estimate the effects of living arrangement on depressive symptoms. RESULTS: A
      total of 16.8 % of the total study population showed depressive symptoms. Living
      with a spouse only was the most common type of living arrangement (46.3 %). Women
      and men living with a spouse only were the least likely to have depressive
      symptoms. However, living without a spouse in a nuclear family and living alone
      were most strongly associated with depressive symptoms in women (OR 1.81; 95 % CI
      1.64-2.00) and men (OR 2.71; 95 % CI 2.43-3.03), respectively. CONCLUSIONS: The
      prevalence of depressive symptoms are associated with the living arrangements of
      elderly Koreans. There are gender differences in these associations, that may
      stem from the different demands of social roles and relationships in the family.

PMID- 24912403
TI  - Effects of glyphosate-based herbicides on survival, development, growth and sex
      ratios of wood frog (Lithobates sylvaticus) tadpoles. II: agriculturally relevant
      exposures to Roundup WeatherMax(r) and Vision(r) under laboratory conditions.
AB  - Glyphosate-based herbicides are currently the most commonly used herbicides in
      the world. They have been shown to affect survival, growth, development and
      sexual differentiation of tadpoles under chronic laboratory exposures but this
      has not been investigated under more environmentally realistic conditions. The
      purpose of this study is (1) to determine if an agriculturally relevant exposure
      to Roundup WeatherMax(r), a relatively new and understudied formulation,
      influences the development of wood frog tadpoles (Lithobates sylvaticus) through
      effects on the mRNA levels of genes involved in the control of metamorphosis; (2)
      to compare results to the well-studied Vision(r) formulation (containing the
      isopropylamine salt of glyphosate [IPA] and polyethoxylated tallowamine [POEA]
      surfactant) and to determine which ingredient(s) in the formulations are
      responsible for potential effects on development; and (3) to compare results to
      recent field studies that used a similar experimental design. In the present
      laboratory study, wood frog tadpoles were exposed to an agriculturally relevant
      application (i.e., two pulses) of Roundup WeatherMax(r) and Vision(r) herbicides
      as well as the active ingredient (IPA) and the POEA surfactant of Vision(r).
      Survival, development, growth, sex ratios and mRNA levels of genes involved in
      tadpole metamorphosis were measured. Results show that Roundup WeatherMax(r)
      (2.89 mg acid equivalent (a.e.)/L) caused 100% mortality after the first pulse.
      Tadpoles treated with a lower concentration of Roundup WeatherMax(r) (0.21 mg
      a.e./L) as well as Vision(r) (2.89 mg a.e./L), IPA and POEA had an increased
      condition factor (based on length and weight measures in the tadpoles) relative
      to controls at Gosner stage (Gs) 36/38. At Gs42, tadpoles treated with IPA and
      POEA had a decreased condition factor. Also at Gs42, the effect on condition
      factor was dependent on the sex of tadpoles and significant treatment effects
      were only detected in males. In most cases, treatment reduced the normal mRNA
      increase of key genes controlling development in tadpoles between Gs37 and Gs42,
      such as genes encoding thyroid hormone receptor beta in brain, glucocorticoid
      receptor in tail and deiodinase enzyme in brain and tail. We conclude that
      glyphosate-based herbicides have the potential to alter mRNA profiles during
      metamorphosis. However, studies in natural systems have yet to replicate these
      negative effects, which highlight the need for more ecologically relevant studies
      for risk assessment.

PMID- 24912402
TI  - The diffusion of a new method of suicide: charcoal-burning suicide in Hong Kong
      and Taiwan.
AB  - PURPOSE: In the late 1990s, an epidemic rise in suicides by carbon monoxide
      poisoning from burning barbecue charcoal began in Hong Kong and Taiwan. This
      study investigates the diffusion of this new method of suicide. METHOD: Official
      mortality data for 1998-2010 in Taiwan and 1998-2009 in Hong Kong were collected;
      overall and method-specific suicide rates in different socio-demographic
      subgroups over the study period were compared. Multiple logistic regression
      analyses were conducted to assess the socio-demographic risk factors for charcoal
      burning vs. non-charcoal-burning suicide. RESULTS: In Hong Kong, the incidence of
      charcoal-burning suicide increased steeply within 1 year of the first reported
      cases, but its use has declined from 24.2% of all suicides during the peak period
      (2002-2004) to 17.1% (2007-2009); in Taiwan, the pace of diffusion was slower in
      onset, but it remains a popular method accounting for 31.0% of all suicides in
      2008-2010. The early adopters in both places tended to be young- and middle-aged
      men. As the epidemic progressed, the method has also been gradually adopted by
      older age groups and women, particularly in Taiwan, but in 2009/10, the method
      still accounted for <8% of suicides in those aged >60 years in both areas.
      CONCLUSIONS: Common features of the epidemic in both places were the greater
      levels of early uptake by the young- and middle-aged males. The different course
      of the charcoal-burning suicide epidemic may reflect social, geographic and media
      reporting differences. Surveillance to identify the emergence of new suicide
      methods is crucial in suicide prevention.

PMID- 24912404
TI  - Heat- and light-induced detachment of the light-harvesting antenna complexes of
      photosystem I in isolated stroma thylakoid membranes.
AB  - The multisubunit pigment-protein complex of photosystem I (PSI) consists of a
      core and peripheral light-harvesting antenna (LHCI). PSI is thought to be a
      rather rigid system and very little is known about its structural and functional
      flexibility. Recent data, however, suggest LHCI detachment from the PSI
      supercomplex upon heat and light treatments. Furthermore, it was suggested that
      the splitting off of LHCI acts as a safety valve for PSI core upon
      photoinhibition (Alboresi et al., 2009). In this work we analyzed the heat- and
      light-induced reorganizations in isolated PSI vesicles (stroma membrane vesicles
      enriched in PSI). Using differential scanning calorimetry we revealed a stepwise
      disassembly of PSI supercomplex above 50 degrees C. Circular dichroism, sucrose
      gradient centrifugation and 77K fluorescence experiments identified the sequence
      of events of PSI destabilization: 3min heating at 60 degrees C or 40min white
      light illumination at 25 degrees C resulted in pronounced Lhca1/4 detachment from
      the PSI supercomplex, which is then followed by the degradation of Lhca2/3. The
      similarity of the main structural effects due to heat and light treatments
      supports the notion that thermo-optic mechanism, structural changes induced by
      ultrafast local thermal transients, which has earlier been shown to be
      responsible for structural changes in the antenna system of photosystem II, can
      also regulate the assembly and functioning of PSI antenna. 

PMID- 24912405
TI  - Ultra-weak delayed luminescence in cancer research: a review of the results by
      the ARETUSA equipment.
AB  - The study of the photoinduced ultraweak photon emission in the optical wavelength
      range, namely the Delayed Luminescence, from human cells and tissues has an
      increasingly growing interest in view of its possible application in optical
      biopsy. Due to the low level, dedicated experimental set-up are necessary to
      reveal such photoluminescence signal. The paper reviews the results obtained in
      the field of cancer research, by using the experimental equipment for fast
      ultraweak luminescence analysis ARETUSA developed at the National Southern
      Laboratories of the National Nuclear Physics Institute (LNS-INFN), in Catania,
      Italy. Delayed Luminescence signals from normal and cancer cells are compared and
      the relationship between Delayed Luminescence and apoptosis is investigated.

PMID- 24912406
TI  - Comments on "Anti-photoaging potential of botulinum toxin type A in UVB-induced
      premature senescence of human dermal fibroblasts in vitro through decreasing
      senescence-related proteins".

PMID- 24912408
TI  - Initial testing (stage 1) of glembatumumab vedotin (CDX-011) by the pediatric
      preclinical testing program.
AB  - BACKGROUND: Glembatumumab vedotin is an antibody-auristatin conjugate that
      targets cells expressing the transmembrane glycoprotein NMB (GPNMB, also known as
      osteoactivin). It has entered clinical evaluation for adult cancers that express
      GPNMB, including melanoma and breast cancer. PROCEDURES: Glembatumumab vedotin
      was administered intravenously at a dose of 2.5 mg/kg using a weekly * 3
      schedule, and its antitumor activity was evaluated against selected Pediatric
      Preclinical Testing Program (PPTP) solid tumor xenografts using standard PPTP
      response metrics. RESULTS: Among PPTP xenografts, GPNMB was primarily expressed
      on the osteosarcoma xenografts, all of which expressed GPNMB at the RNA level,
      although at varying levels. Protein expression assessed by immunohistochemistry
      (IHC) showed variation across the osteosarcoma xenografts with one model showing
      no tumor cell expression. Glembatumumab vedotin induced statistically significant
      differences (P < 0.05) in event-free survival (EFS) distribution compared to
      control in each of the six osteosarcoma models studied. Three of six osteosarcoma
      xenografts demonstrated a maintained complete response (MCR). Two other
      xenografts showed progressive disease with growth delay, while the final
      xenograft showed progressive disease with no growth delay. Two of the
      osteosarcoma xenografts with MCRs showed the highest GPNMB expression at the RNA
      level. Conversely, the xenograft with the lowest GPNMB mRNA expression had the
      poorest response to glembatumumab vedotin. Two rhabdomyosarcoma xenografts that
      did not express GPNMB showed limited responses to glembatumumab vedotin.
      CONCLUSIONS: Glembatumumab vedotin yielded high-level activity against three of
      six osteosarcoma xenografts, with evidence for response being related to GPNMB
      expression levels.

PMID- 24912409
TI  - Raman scattering of linear chains of strongly coupled Ag nanoparticles on SWCNTs.
AB  - We compare the Raman scattering properties of hybrid nanostructures consisting of
      Ag nanoparticles (NPs) in disordered and aligned arrangements on single-walled
      carbon nanotubes (SWCNTs) as a result of chemical and photoreduction methods. In
      the latter case, the unique structure of the very small Ag NP (from 4 to 7 nm)
      chains generated an extremely large mode at 969 cm(-1) that was assigned to the
      sulphate-silver interaction at the NP surface. Another strong mode was present at
      1201 cm(-1) and was assigned to an IR-active mode of sodium dodecyl sulphate
      (SDS); this mode was observed because the symmetry changes altered the selection
      rules. We demonstrate that both the UV photoreduction of silver and the presence
      of SWCNTs are necessary to produce this very strong Raman scattering. The Raman
      modes of the SWCNTs are also significantly modified by the presence of Ag NP
      chains along the nanotubes.

PMID- 24912407
TI  - Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways
      in the intestine.
AB  - BACKGROUND: Berberine is known to improve glucose and lipid metabolism disorders,
      but it poorly absorbed into the blood stream from the gut. Therefore, the exact
      underlying mechanism for berberine is still unknown. In this study, we
      investigated the effect of berberine on glucose metabolism in diabetic rats and
      tested the hypothesis that berberine acts directly in the terminal ileums.
      METHODS: Rats were divided into a control group, diabetic group (DM), low dose of
      berberine group (BerL) and high dose of berberine group (BerH). Ileum samples
      were analyzed using a Roche NimbleGen mRNA array, qPCR and immunohistochemistry.
      RESULTS: We found that 8 weeks of treatment with berberine significantly
      decreased fasting blood glucose levels. An oral glucose tolerance test (OGTT)
      showed that blood glucose was significantly reduced in the BerL and BerH groups
      before and at 30 min, 60 min and 120 min after oral glucose administration.
      Plasma postprandial glucagon-like peptide-1 (GLP-1) levels were increased in the
      berberine-treated groups. The ileum from the BerH group had 2112 genes with
      significantly changed expression (780 increased, 1332 decreased). KEGG pathway
      analyses indicated that all differentially expressed genes included 9 KEGG
      pathways. The top two pathways were the MAPK signaling pathway and the GnRH
      signaling pathway. Q-RT-PCR and immunohistochemistry verified that glucagon-like
      peptide 1 receptor (Glp1r) and mitogen activated protein kinase 10 (Mapk10) were
      significantly up-regulated, in contrast, gonadotropin releasing hormone receptor
      (Gnrhr) and gonadotropin-releasing hormone 1 (Gnrh1) were down-regulated in the
      BerH group. CONCLUSION: Our data suggest that berberine can improve blood glucose
      levels in diabetic rats. The mechanisms involved may be in the MAPK and GnRh-Glp
      1 pathways in the ileum.

PMID- 24912410
TI  - Effect of certificate of need law on emergency department length of stay.
AB  - BACKGROUND: The impact of the Certificate of Need (CON) law on Emergency
      Department (ED) care remains elusive in the academic literature. OBJECTIVES: We
      study the impact of CON law on ED Length of Stay (LOS). METHODS: We examine ED
      LOS to detect any statistically significant difference between CON and non-CON
      states. We then estimate the effects of CON law on ED LOS by treating CON as an
      exogenous (endogenous) variable. RESULTS: We find that the CON legislation
      positively impacts ED care by reducing ED LOS (95% confidence interval [CI] -61.3
      to -10.3), and we can't reject the hypothesis that the CON legislation can be
      treated as an exogenous variable in our model. An increase in the stringency of
      the CON law (measured by the threshold on equipment expenditure that is subject
      to a CON review) tends to diminish this positive impact on ED LOS (95% CI 9.9
      68.0). The party affiliation of the Governor (95% CI 10.3-37.5), the political
      environment as a function of the agreement on voting between state senators (95%
      CI-64.8 to -12.9), proportion of young population (0-17 years) when compared with
      the elderly (>65 years) (95% CI-2299.7 to -184.1), proportion of population
      covered by privately purchased insurance (95% CI-819.3 to -59.9), etc., are found
      to significantly impact ED LOS in a state. CONCLUSION: This study provides a
      better understanding of the impact of CON law on ED care, which extends the
      previous literature that has mainly focused on CON effects on inpatient care.

PMID- 24912411
TI  - Desensitization outcomes: quantifying and questioning.

PMID- 24912412
TI  - A novel mutation of the axonemal dynein heavy chain gene 5 (DNAH5) in a Japanese
      neonate with asplenia syndrome.
AB  - Asplenia syndrome (Ivemark syndrome) is a complex disorder composed of asplenia,
      malpositioning of the visceral organs and congenital heart defects. To elucidate
      the underlying molecular mechanism of asplenia syndrome, we herein analyzed the
      fatal case of a male neonate who exhibited three lobes of the left lung, asplenia
      and complex heart anomalies and died 6 hours after delivery. A whole-exome
      sequence (WES) analysis followed by Sanger sequence identified a heterozygous
      single nucleotide change (c.7829A>G) in exon 47 of the axonemal dynein heavy
      chain gene 5 (DNAH5), which results in the missense mutation of p.Glu2610Gly.
      This mutation was found only in the neonate, but not in his parents, implying de
      novo mutation of DNAH5 that codes dynein heavy chain, a component of outer dynein
      arm. The WES analysis also identified a heterozygous single nucleotide
      substitution (c.3697C>T) in the axonemal dynein heavy chain gene 7 (DNAH7),
      resulting in p.Arg1233Cys, and a rare SNP (c.2029G>A, p.Gly677Ser) of the
      axonemal dynein intermediate chain gene 1 (DNAI1) in the patient and his mother,
      but not in his father. The mutation of p.Glu2610Gly in DNAH5 is novel and we here
      present a first Japanese case of asplenia syndrome who exhibited a DNAH5
      mutation. 

PMID- 24912413
TI  - Freeze-all can be a superior therapy to another fresh cycle in patients with
      prior fresh blastocyst implantation failure.
AB  - Implantation failure has various causes, including impaired uterine receptivity
      following ovarian stimulation. This retrospective cohort study compared outcomes
      in patients with prior implantation failure who elected to undergo another fresh
      cycle versus those who opted for embryo cohort cryopreservation (freeze-all) and
      subsequent thaw. There were 269 patients with implantation failure following
      fresh autologous blastocyst transfer opting to undergo a subsequent cycle, with
      163 choosing another fresh cycle and 106 electing freeze-all and subsequent thaw.
      Multiple logistic regression analysis indicated that cohort cryopreservation was
      associated with greater chance of live birth when compared with another fresh
      cycle (P < 0.0001). The odds ratio for live birth with freeze-all relative to a
      fresh cycle was 3.8 (95% CI 2.1-7.2). A second analysis was then performed using
      cumulative live birth rate as the outcome measure. Multiple logistic regression
      indicated freeze-all was associated with greater cumulative live birth rate than
      was a fresh cycle (OR 1.9, 95% CI 1.1-3.3, P = 0.0287). These findings suggest
      that, following implantation failure with fresh blastocysts, patients have a
      significantly greater chance of live birth with freeze-all and subsequent thaw
      than with another fresh cycle. 

PMID- 24912414
TI  - A novel Alu-mediated microdeletion at 11p13 removes WT1 in a patient with
      cryptorchidism and azoospermia.
AB  - This article describes a patient with cryptorchidism and nonobstructive
      azoospermia presenting a novel microdeletion of approximately 1 Mb at 11p13. It
      was confirmed by multiplex ligation-dependent probe amplification that this
      heterozygous deletion spanned nine genes (WT1, EIF3M, CCDC73, PRRG4, QSER1,
      DEPDC7, TCP11L1, CSTF3 and HIPK3) and positioned the breakpoints within highly
      homologous repetitive elements. As far as is known, this is the smallest deletion
      as-yet described encompassing the WT1 gene and was detected only once in a total
      of 32 Portuguese patients with isolated uni- or bilateral cryptorchidism. These
      findings suggest that molecular analysis in patients with genitourinary features
      suggestive of WT1 impairment, namely cryptorchidism and renal abnormalities, may
      reveal cryptic genetic defects. 

PMID- 24912415
TI  - Analysis of CGG repeats in FMR1 in Chinese women with idiopathic premature
      ovarian failure.
AB  - Excessive triple CGG repeats in the FMR1 gene have been widely associated with
      premature ovarian failure. The number of AGG interruptions and length of
      uninterrupted CGG repeats have been correlated with repeat instability on
      transmission. In this study, FMR1 CGG repeats and AGG interruption status were
      determined by triplet-primed PCR in 117 premature ovarian failure patients and 82
      matched controls. A possible relationship between CGG repeats or AGG interruption
      and serum FSH concentrations in patients and controls was evaluated. One patient
      had a premutation allele (73 repeats) (1/117), while no such mutations were
      observed in controls (0/82). Other patients and all controls had CGG repeats in
      the normal range. There was no significant difference in the incidence of
      intermediate mutations of CGG repeats between patients and controls and no
      relationship between CGG repeats with serum FSH concentrations. Interestingly,
      more individuals with premature ovarian failure carried no AGG interruptions than
      the controls (4.27% versus 1.83%) but statistical significance was not reached.
      This small case-control study failed to find associations between CGG repeat
      sizes or AGG interruptions in FMR1 and premature ovarian failure in Chinese
      women. Further study with large sample size is warranted. 

PMID- 24912416
TI  - Concerning Tetsuya Ishii's article: potential impact of human mitochondrial
      replacement on global policy regarding germline gene modification.

PMID- 24912417
TI  - AMH and AMHR2 genetic variants in Chinese women with primary ovarian
      insufficiency and normal age at natural menopause.
AB  - The aim of this study was to investigate the role of the anti-Mullerian hormone
      (AMH) signalling pathway in the pathophysiology of idiopathic primary ovarian
      insufficiency (POI) and age at natural menopause (ANM) using a genetic approach.
      DNA sequencing was used to detect the genotype distribution and allele frequency
      of the genes AMH and AMH receptor II (AMHR2) in 120 cases of idiopathic POI and
      120 normal-ANM women. Fourteen sequence variants of AMHR2, including 10 novel
      variants, were identified. Two novel exonic missense variants were p.I209N and
      p.L354F. The missense variant p.I209N, which is conserved in different species,
      was predicted to have functional and structural impacts on the AMHR2 protein. The
      clinical significance of one additional variant (p.L354F) remains arguable
      pending functional studies. The genotype frequencies of AMH and AMHR2 were
      similar in distribution for POI patients and normal-ANM women. These findings
      suggest that POI patients and normal-ANM women in China share AMH and AMHR2
      genetic variants. The AMH signalling pathway associated with ANM also may
      contribute to POI. 

PMID- 24912418
TI  - Limitations of a time-lapse blastocyst prediction model: a large multicentre
      outcome analysis.
AB  - The goal of embryo selection models is to select embryos with the highest
      reproductive potential, whilst minimizing the rejection of viable embryos.
      Ultimately, any embryo selection model must be tested on clinical outcome. We
      therefore retrospectively tested a published blastocyst prediction model on a
      large combined set of transferred embryos with known clinical outcome. The model
      was somewhat effective in that we found a relative increase of 30% for
      implantation in the model-selected group of embryos. There was, however, a
      concomitant large rejection of embryos from our test cohort, which actually
      resulted in pregnancy. This hypothetical experiment highlights the limitations of
      predicting blastulation only. Crucially, it illustrates that both sensitivity and
      specificity are important parameters when developing embryo selection models for
      prospective clinical use. 

PMID- 24912419
TI  - International harmonization and mitochondrial replacement.

PMID- 24912420
TI  - Coasting, embryo development and outcomes of blastocyst transfer: a case-control
      study.
AB  - This study compared the effect on blastocyst development and clinical outcome of
      coasting in women at increased risk of moderate-severe ovarian hyperstimulation
      syndrome (OHSS; n=389) with a control group matched for age and basal FSH that
      did not undergo coasting (n=386) in IVF/intracytoplasmic sperm injection (ICSI)
      cycles. The main outcome measures were rate of blastocyst development and live
      birth. More cycles progressed to the blastocyst stage in the coasted group
      (n=169) compared with the control group (n=83; 43.4% versus 21.5%; P<0.001). The
      biochemical pregnancy, clinical pregnancy and live birth rates were similar
      (46.5% versus 42.0%; 40.6% versus 37.8%; 31.6% versus 30.1%). The duration of
      coasting up to 4 days did not affect progression to blastocyst stage. The
      multivariate model showed that coasting (OR 1.73, P=0.004) and the number of
      oocytes retrieved (OR 1.17, P=0.001) were positively correlated with blastocyst
      formation. Coasting, a measure to reduce the risk of OHSS, does not impair
      blastocyst development or clinical outcome. Coasting should remain an effective
      measure to prevent OHSS.

PMID- 24912421
TI  - How and why mitochondrial replacement gets our vote.

PMID- 24912422
TI  - MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of
      colorectal cancer by repressing PTEN expression.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide,
      especially in Western countries. Although chemotherapy is used as an adjuvant or
      as a palliative treatment, drug resistance poses a great challenge. This study
      intended to identify biomarkers as predictive factors for chemotherapy. PATIENTS
      AND METHODS: By microarray analysis, we studied miRNAs expression profiles in CRC
      patient, comparing chemoresistant and chemosensitive groups. The miRNAs of
      interest were validated and the impact on clinical outcomes was assessed in a
      cohort of 295 patients. To search for potential targets of these miRNAs, tissue
      samples were subject to in situ hybridization and immunohistochemistry analysis.
      Colorectal adenocarcinoma cells were also used for in vitro experimentation,
      where cellular invasiveness and drug resistance were examined in miRNA
      transfected cells. RESULTS: The expression level of miRNA-17-5p was found
      increased in chemoresistant patients. Significantly higher expression levels of
      miR-17-5p were found in CRC patients with distant metastases and higher clinical
      stages. Kaplan-Meier analysis showed that CRC patients with higher levels of miR
      17-5p had reduced survival, especially in patients who had previously received
      chemotherapy. Overexpression of miR-17-5p promoted COLO205 cell invasiveness. We
      found that PTEN was a target of miR-17-5p in the colon cancer cells, and their
      context-specific interactions were responsible for multiple drug-resistance.
      Chemotherapy was found to increase the expression levels of miR-17-5p, which
      further repressed PTEN levels, contributing to the development of chemo
      resistance. CONCLUSIONS: MiR-17-5p is a predictive factor for chemotherapy
      response and a prognostic factor for overall survival in CRC, which is due to its
      regulation of PTEN expression.

PMID- 24912423
TI  - High-density lipoprotein 3 and apolipoprotein A-I alleviate platelet storage
      lesion and release of platelet extracellular vesicles.
AB  - BACKGROUND: Stored platelet (PLT) concentrates (PLCs) for transfusion develop a
      PLT storage lesion (PSL), decreasing PLT viability and function with profound
      lipidomic changes and PLT extracellular vesicle (PL-EV) release. High-density
      lipoprotein 3 (HDL3 ) improves PLT homeostasis through silencing effects on PLT
      activation in vivo. This prompted us to investigate HDL3 and apolipoprotein A-I
      (apoA-I) as PSL-antagonizing agents. STUDY DESIGN AND METHODS: Healthy donor PLCs
      were split into low-volume standard PLC storage bags and incubated with native
      (n)HDL3 or apoA-I from plasma ethanol fractionation (precipitate IV) for 5 days
      under standard blood banking conditions. Flow cytometry, Born aggregometry, and
      lipid mass spectrometry were carried out to analyze PL-EV release, PLT
      aggregation, agonist-induced PLT surface marker expression, and PLT and plasma
      lipid compositions. RESULTS: Compared to control, added nHDL3 and apoA-I
      significantly reduced PL-EV release by up to -62% during 5 days, correlating with
      the added apoA-I concentration. At the lipid level, nHDL3 and apoA-I antagonized
      PLT lipid loss (+12%) and decreased cholesteryl ester (CE)/free cholesterol (FC)
      ratios (-69%), whereas in plasma polyunsaturated/saturated CE ratios increased
      (+3%) and CE 16:0/20:4 ratios decreased (-5%). Administration of nHDL3 increased
      PLT bis(monoacylglycero)phosphate/phosphatidylglycerol (+102%) and phosphatidic
      acid/lysophosphatidic acid (+255%) ratios and improved thrombin receptor
      activating peptide 6-induced PLT aggregation (+5%). CONCLUSION: nHDL3 and apoA-I
      improve PLT membrane homeostasis and intracellular lipid processing and increase
      CE efflux, antagonizing PSL-related reduction in PLT viability and function and
      PL-EV release. We suggest uptake and catabolism of nHDL3 into the PLT open
      canalicular system. As supplement in PLCs, nHDL3 or apoA-I from Fraction IV of
      plasma ethanol fractionation have the potential to improve PLC quality to prolong
      storage.

PMID- 24912424
TI  - Medication errors related to transdermal opioid patches: lessons from a regional
      incident reporting system.
AB  - OBJECTIVE: A few cases of adverse reactions linked to erroneous use of
      transdermal opioid patches have been reported in the literature. The aim of this
      study was to describe and characterize medication errors (MEs) associated with
      use of transdermal fentanyl and buprenorphine. METHODS: All events concerning
      transdermal opioid patches reported between 2004 and 2011 to a regional incident
      reporting system and assessed as MEs were scrutinized and characterized. MEs were
      defined as "a failure in the treatment process that leads to, or has the
      potential to lead to, harm to the patient". RESULTS: In the study 151 MEs were
      identified. The three most common error types were wrong administration time 67
      (44%), wrong dose 34 (23%), and omission of dose 20 (13%). Of all MEs, 118 (78%)
      occurred in the administration stage of the medication process. Harm was reported
      in 26 (17%) of the included cases, of which 2 (1%) were regarded as serious harm
      (nausea/vomiting and respiratory depression). Pain was the most common adverse
      reaction reported. CONCLUSIONS: Of the reported MEs related to transdermal
      fentanyl and buprenorphine, most occurred during administration. Improved
      routines to ascertain correct and timely administration and educational
      interventions to reduce MEs for these drugs are warranted.

PMID- 24912425
TI  - Modified glabellar rhytid incision for frontal sinus trephination.

PMID- 24912426
TI  - Healed porcine incisions previously treated with a surgical incision management
      system: mechanical, histomorphometric, and gene expression properties.
AB  - BACKGROUND: Computer and bench models have shown previously that surgical
      incision management with negative pressure (SIM) immediately decreases lateral
      tissue tension and increases incisional apposition. Better apposition is known to
      improve healing. Thus, SIM was hypothesized to improve the quality of incisional
      healing. This study evaluated the impact that 5 days of SIM had on mechanical
      properties and associated changes in the histology/histomorphometry and gene
      expression of healed porcine incisions. METHODS: One incision in each of the 4
      pairs of contralateral, sutured, full-thickness incisions in each of 6 Yucatan
      swine were treated with either SIM (PrevenaTM Incision Management System; n = 24
      incisions/treatment group) or standard of care (SOC; sterile absorbent abdominal
      pads; n = 24/group) for 5 days, after which both groups received SOC for an
      additional 5 days. Biopsies for gene-expression analyses were collected on days 5
      (n = 6 pairs/group), 20 (n = 6 pairs/group), and 40 (n = 12 pairs/group). On day
      40, the animals were killed, after which healed incisions were harvested for
      mechanical testing (n = 12/group) and histologic/histomorphometric evaluation (n
      = 12/group). RESULTS: Compared with SOC-treated incisions, SIM-treated incisions
      had significantly improved (p < 0.05) mechanical properties (strain energy
      density, peak strain) and a narrower scar/healed area in the deep dermis on day
      40. Differences in gene expression between SOC- and SIM-treated specimens were
      observed primarily on day 5. The SIM-treated specimens had significantly fewer
      genes, which were differentially expressed and showed reduced upregulation of
      genes associated with inflammation, hypoxia, retardation of reepithelialization,
      impaired wound healing, and scarring. CONCLUSION: Early application of SIM
      improved the quality of healed porcine incisions in terms of mechanical,
      histomorphometric, and gene-expression properties. NO LEVEL ASSIGNED: This
      journal requires that authors assign a level of evidence to each submission to
      which Evidence-Based Medicine rankings are applicable. This excludes Review
      Articles, Book Reviews, and manuscripts that concern Basic Science, Animal
      Studies, Cadaver Studies, and Experimental Studies. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 24912427
TI  - Facelift complications related to median and peak blood pressure evaluation.
AB  - BACKGROUND: Hematoma remains the most challenging complication of facelifting and
      has been associated with male sex, hypertension, aspirin use, smoking, and high
      body mass index. Patients who underwent a facelift were studied to determine
      rates of hematoma and other complications and to identify predictive and
      protective factors, including meticulous analysis of perioperative blood
      pressure. METHODS: Charts of patients who underwent a facelift from 2003 to 2011
      at our institution were retrospectively reviewed. Demographic, clinical, and
      procedural data were collected. All postoperative complications were recorded.
      Data from continuous blood pressure monitoring in the operating and recovery
      rooms were obtained from a perioperative database and stratified by median and
      peak values. Logistic regression was used for data analysis. RESULTS: Of the 229
      patients included, the majority were female (88.2 %), mean age at presentation
      was 62 years, and 35.8 % had hypertension. Postoperative complications occurred
      in 60 patients (26.2 %). The most common complication was unfavorable scar (7.4
      %), followed by hematoma (6.5 %). Male sex (P = 0.02), history of hypertension (P
      = 0.04), preoperative systolic blood pressure (SBP) greater than 160 mmHg (P =
      0.04), and operating room peak SBP greater than 165 mmHg (P = 0.04) were
      predictive factors for hematoma. Recovery room peak SBP greater than 150 mmHg (P
      = 0.09) was also associated with hematoma. On multivariate analysis, only male
      sex and preoperative SBP greater than 160 mmHg remained independent risk factors
      for hematoma. CONCLUSIONS: This study is unique in that it compares the rate of
      hematoma to continuous blood pressure data in the operating and recovery rooms
      stratified by median and peak values. Meticulous control of perioperative SBP is
      recommended for a safe facelift. History of hypertension, increased SBP at
      admission, and increased perioperative peak SBP are predictors for postoperative
      hematoma. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 24912428
TI  - Diced cartilage combined with warm blood glue for nasal dorsum enhancement.

PMID- 24912429
TI  - Aesthetic shoulder augmentation with silicone implants.

PMID- 24912430
TI  - Early assessment of minimal residual disease in AML by flow cytometry during
      aplasia identifies patients at increased risk of relapse.
AB  - In acute myeloid leukemia (AML), assessment of minimal residual disease (MRD) by
      flow cytometry (flow MRD) after induction and consolidation therapy has been
      shown to provide independent prognostic information. However, data on the value
      of earlier flow MRD assessment are lacking. Therefore, the value of flow MRD
      detection was determined during aplasia in 178 patients achieving complete
      remission after treatment according to AMLCG (AML Cooperative Group) induction
      protocols. Flow MRD positivity during aplasia predicted poor outcome (5-year
      relapse-free survival (RFS) 16% vs 43%, P<0.001) independently from age and
      cytogenetic risk group (hazard ratio for MRD positivity 1.71; P=0.009).
      Importantly, the prognosis of patients without detectable MRD was neither
      impacted by morphological blast count during aplasia nor by MRD status
      postinduction. Early flow MRD was also evaluated in the context of existing risk
      factors. Flow MRD was prognostic within the intermediate cytogenetic risk group
      (5-year RFS 15% vs 37%, P=0.016) as well as for patients with normal karyotype
      and NPM1 mutations (5-year RFS 13% vs 49%, P=0.02) or FLT3-ITD (3-year RFS rates
      9% vs 44%, P=0.016). Early flow MRD assessment can improve current risk
      stratification approaches by prediction of RFS in AML and might facilitate
      adaptation of postremission therapy for patients at high risk of relapse. 

PMID- 24912431
TI  - The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes
      resistance to ibrutinib and other agents used in the treatment of Waldenstrom's
      Macroglobulinemia.
AB  - CXCR4(WHIM) somatic mutations are common Waldenstrom's Macroglobulinemia (WM),
      and are associated with clinical resistance to ibrutinib. We engineered WM cells
      to express the most common WHIM (Warts, Hypogammaglobulinemia, Infections and
      Myelokathexis), CXCR(S338X) mutation in WM. Following SDF-1a stimulation,
      CXCR4(S338X) WM cells exhibited decreased receptor internalization, enhanced and
      sustained AKT kinase (AKT) and extracellular regulated kinase (ERK) signaling,
      decreased poly (ADP-ribose) polymerase and caspase 3 cleavage, and decreased
      Annexin V staining versus CXCR4 wild-type (WT) cells. CXCR4(S338X)-related
      signaling and survival effects were blocked by the CXCR4 inhibitor AMD3100. SDF
      1a-treated CXCR4(S338X) WM cells showed sustained AKT and ERK activation and
      decreased apoptotic changes versus CXCR4(WT) cells following ibrutinib treatment,
      findings which were also reversed by AMD3100. AKT or ERK antagonists restored
      ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells
      demonstrating their role in SDF-1a-mediated ibrutinib resistance. Enhanced bone
      marrow pAKT staining was also evident in CXCR4(WHIM) versus CXCR4(WT) WM
      patients, and remained active despite ibrutinib therapy in CXCR4(WHIM) patients.
      Last, CXCR4(S338X) WM cells showed varying levels of resistance to other WM
      relevant therapeutics, including bendamustine, fludarabine, bortezomib and
      idelalisib in the presence of SDF-1a. These studies demonstrate a functional role
      for CXCR4(WHIM) mutations, and provide a framework for investigation of CXCR4
      inhibitors in WM. 

PMID- 24912432
TI  - Improving secondary ion mass spectrometry image quality with image fusion.
AB  - The spatial resolution of chemical images acquired with cluster secondary ion
      mass spectrometry (SIMS) is limited not only by the size of the probe utilized to
      create the images but also by detection sensitivity. As the probe size is reduced
      to below 1 MUm, for example, a low signal in each pixel limits lateral resolution
      because of counting statistics considerations. Although it can be useful to
      implement numerical methods to mitigate this problem, here we investigate the use
      of image fusion to combine information from scanning electron microscope (SEM)
      data with chemically resolved SIMS images. The advantage of this approach is that
      the higher intensity and, hence, spatial resolution of the electron images can
      help to improve the quality of the SIMS images without sacrificing chemical
      specificity. Using a pan-sharpening algorithm, the method is illustrated using
      synthetic data, experimental data acquired from a metallic grid sample, and
      experimental data acquired from a lawn of algae cells. The results show that up
      to an order of magnitude increase in spatial resolution is possible to achieve. A
      cross-correlation metric is utilized for evaluating the reliability of the
      procedure.

PMID- 24912434
TI  - Electron flood gun damage effects in 3D secondary ion mass spectrometry imaging
      of organics.
AB  - Electron flood guns used for charge compensation in secondary ion mass
      spectrometry (SIMS) cause chemical degradation. In this study, the effect of
      electron flood gun damage on argon cluster depth profiling is evaluated for
      poly(vinylcarbazole), 1,4-bis((1-naphthylphenyl)amino)biphenyl and Irganox 3114.
      Thin films of these three materials are irradiated with a range of doses from a
      focused beam of 20 eV electrons used for charge neutralization. SIMS chemical
      images of the irradiated surfaces show an ellipsoidal damaged area, approximately
      3 mm in length, created by the electron beam. In depth profiles obtained with 5
      keV Ar(2000)(+) sputtering from the vicinity of the damaged area, the
      characteristic ion signal intensity rises from a low level to a steady state. For
      the damaged thin films, the ion dose required to sputter through the thin film to
      the substrate is higher than for undamaged areas. It is shown that a damaged
      layer is formed and this has a sputtering yield that is reduced by up to an order
      of magnitude and that the thickness of the damaged layer, which increases with
      the electron dose, can be as much as 20 nm for Irganox 3114. The study emphasizes
      the importance of minimizing the neutralizing electron dose prior to the
      analysis.

PMID- 24912433
TI  - Revealing ligand binding sites and quantifying subunit variants of noncovalent
      protein complexes in a single native top-down FTICR MS experiment.
AB  - "Native" mass spectrometry (MS) has been proven to be increasingly useful for
      structural biology studies of macromolecular assemblies. Using horse liver
      alcohol dehydrogenase (hADH) and yeast alcohol dehydrogenase (yADH) as examples,
      we demonstrate that rich information can be obtained in a single native top-down
      MS experiment using Fourier transform ion cyclotron mass spectrometry (FTICR MS).
      Beyond measuring the molecular weights of the protein complexes, isotopic mass
      resolution was achieved for yeast ADH tetramer (147 kDa) with an average
      resolving power of 412,700 at m/z 5466 in absorption mode, and the mass reflects
      that each subunit binds to two zinc atoms. The N-terminal 89 amino acid residues
      were sequenced in a top-down electron capture dissociation (ECD) experiment,
      along with the identifications of the zinc binding site at Cys46 and a point
      mutation (V58T). With the combination of various activation/dissociation
      techniques, including ECD, in-source dissociation (ISD), collisionally activated
      dissociation (CAD), and infrared multiphoton dissociation (IRMPD), 40% of the
      yADH sequence was derived directly from the native tetramer complex. For hADH,
      native top-down ECD-MS shows that both E and S subunits are present in the hADH
      sample, with a relative ratio of 4:1. Native top-down ISD of the hADH dimer shows
      that each subunit (E and S chains) binds not only to two zinc atoms, but also the
      NAD/NADH ligand, with a higher NAD/NADH binding preference for the S chain
      relative to the E chain. In total, 32% sequence coverage was achieved for both E
      and S chains.

PMID- 24912435
TI  - Energetics and kinetics of thermal ionization models of MALDI.
AB  - Thermal models of ultraviolet MALDI ionization based on the polar fluid concept
      are re-examined. Key components are very high solvating power of the fluidized
      matrix and consequent low reaction-free energy, attainment of thermal equilibrium
      in the fluid, and negligible recombination losses. None of these are found to
      hold in a MALDI event. The reaction-free energy in the hot matrix must be near
      the gas phase value, ion formation is too slow to approach equilibrium, and
      geminate recombination of autoprotolysis pairs greatly increases the initial loss
      rate. The maximum thermal ion yield is estimated to be many orders of magnitude
      below experimental values. 

PMID- 24912436
TI  - Neonatal diabetes with intractable epilepsy: DEND syndrome.
AB  - Permanent Neonatal Diabetes Mellitus (PNDM), is a rare monogenic disorder, caused
      by activating mutations of the KATP channel. The most severe clinical form of
      PNDM presents as Developmental delay, Epilepsy and Neonatal Diabetes (DEND)
      syndrome. Diagnosis is confirmed by genetic mutation testing. Oral sulfonylurea
      therapy improves neurological outcome. 

PMID- 24912437
TI  - Fanconi-Bickel syndrome - mutation in SLC2A2 gene.
AB  - Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of
      carbohydrate metabolism. The defect in the GLUT 2 receptors in the hepatocytes,
      pancreas and renal tubules leads to symptoms secondary to glycogen storage,
      glucose metabolism and renal tubular dysfunction. Derangement in glucose
      metabolism is classical with fasting hypoglycemia and post-prandial
      hyperglycemia. The authors report a 4-year-old boy who presented with failure to
      thrive, motor delay, protuberant abdomen and was noted to have huge hepatomegaly
      with glycogen deposition in liver, and renal tubular acidosis. Gene sequencing
      revealed homozygous mutation, c.1330T > C in SLC2A2 gene, thus confirming the
      diagnosis of FBS. Only three mutations have been reported from India so far. The
      primary reason for referral to authors' hospital was for liver transplantation,
      but an accurate diagnosis led to avoidance of the major surgery and streamlining
      of treatment with clinical benefit to the child and family. 

PMID- 24912438
TI  - Infantile Budd Chiari and response to balloon dilatation.

PMID- 24912439
TI  - Molecular diagnosis of enteroviruses associated with Hand, Foot and Mouth Disease
      (HFMD).

PMID- 24912440
TI  - Syndrome of insulin resistance with acanthosis nigricans, acral hypertrophy and
      muscle cramps in an adolescent - a rare diagnosis revisited.
AB  - The authors report a 14-y-old boy with insulin resistance, acanthosis nigricans,
      acral hypertrophy and muscle cramps. While there was a dramatic response of the
      muscle cramps to phenytoin therapy, some other features of metabolic syndrome did
      not respond to phenytoin therapy alone. 

PMID- 24912441
TI  - Antibiotics in the first week of life is a risk factor for allergic rhinitis at
      school age.
AB  - BACKGROUND: Heredity as well as external factors influences the development of
      allergic rhinitis. The aim of this study was to analyse early risk factors and
      protective factors for allergic rhinitis at school age. METHODS: This is a
      prospective, longitudinal study of children born in western Sweden in 2003 where
      50% of the birth cohort was randomly selected. The parents answered
      questionnaires at 6 months, 12 months, 4.5 yr and 8 yr. At 8 yr, 5044
      questionnaires were distributed. Of these, 4051 responded, that is, 80.3%.
      Current allergic rhinitis was defined as symptoms and use of medication during
      the past 12 months. RESULTS: Current allergic rhinitis at 8 yr was reported by
      10.9%. Mean onset age was 5.7 yr, and 61.9% were boys. In a multivariate
      analysis, antibiotics in the first week of life increased the risk of allergic
      rhinitis (adjusted odds ratio 1.75, 95% confidence interval (1.03, 2.97)).
      Increased risk was also seen with parental allergic rhinitis (aOR 2.73 (2.12,
      3.52)), food allergy first year (aOR 2.45 (1.61, 3.73)), eczema first year (aOR
      1.97 (1.50, 2.59)) and male gender (aOR 1.35 (1.05, 1.74)). Living on a farm at
      4.5 yr reduced the risk (aOR 0.31 (0.13, 0.78)). CONCLUSION: Antibiotics in the
      first week of life increased the risk of allergic rhinitis at school age, while
      living on a farm at preschool age reduced the risk. Both findings are compatible
      with the hygiene hypothesis.

PMID- 24912442
TI  - Distinct alterations in ATP-binding cassette transporter expression in liver,
      kidney, small intestine, and brain in adjuvant-induced arthritic rats.
AB  - Pathophysiological changes of infection or inflammation are associated with
      alterations in the production of numerous absorption, distribution, metabolism
      and excretion-related proteins. However, little information is available on the
      effects of inflammation on the expression levels and activities of ATP-binding
      cassette (ABC) transporters. We examined the effect of acute (on day 7) and
      chronic (on day 21) inflammation on the expression of ABC transporters in some
      major tissues in rat. Adjuvant-induced arthritis (AA) in rats was used as an
      animal model for inflammation. The mRNA levels of mdr1a and mdr1b encoding P
      glycoprotein (P-gp) decreased significantly in livers of AA rats on day 21.
      Hepatic protein levels of P-gp, Mrp2, and Bcrp decreased significantly in
      membranes but not homogenates of AA rats after 7 days and after 21 days of
      treatment with adjuvant. Contrary to liver, protein levels of P-gp and Mrp2, but
      not Bcrp in kidney, increased significantly in membranes. The biliary excretion
      of rhodamine 123 was decreased in rats with chronic inflammation owing to
      decreases in efflux activities of P-gp. Our results showed that the expression of
      transporters in response to inflammation was organ dependent. In particular,
      hepatic and renal P-gp and Mrp2 exhibited opposite changes in membrane protein
      levels.

PMID- 24912443
TI  - Mechanisms of the beneficial effects of Ger-Gen-Chyn-Lian-Tang on acute and
      chronic liver injury.

PMID- 24912444
TI  - Catheter ablation in the role of rescuer in treatment of recurrent atrial
      fibrillation following surgical ablation.

PMID- 24912445
TI  - ABCC transporters mediate insect resistance to multiple Bt toxins revealed by
      bulk segregant analysis.
AB  - BACKGROUND: Relatively recent evidence indicates that ABCC2 transporters play a
      main role in the mode of action of Bacillus thuringiensis (Bt) Cry1A-type
      proteins. Mapping of major Cry1A resistance genes has linked resistance to the
      ABCC2 locus in Heliothis virescens, Plutella xylostella, Trichoplusia ni and
      Bombyx mori, and mutations in this gene have been found in three of these Bt
      resistant strains. RESULTS: We have used a colony of Spodoptera exigua (Xen-R)
      highly resistant to a Bt commercial bioinsecticide to identify regions in the S.
      exigua genome containing loci for major resistance genes by using bulk segregant
      analysis (BSA). Results reveal a region containing three genes from the ABCC
      family (ABBC1, ABBC2 and ABBC3) and a mutation in one of them (ABBC2) as
      responsible for the resistance of S. exigua to the Bt commercial product and to
      its key Spodoptera-active ingredients, Cry1Ca. In contrast to all previously
      described mutations in ABCC2 genes that directly or indirectly affect the
      extracellular domains of the membrane protein, the ABCC2 mutation found in S.
      exigua affects an intracellular domain involved in ATP binding. Functional
      analyses of ABBC2 and ABBC3 support the role of both proteins in the mode of
      action of Bt toxins in S. exigua. Partial silencing of these genes with dsRNA
      decreased the susceptibility of wild type larvae to both Cry1Ac and Cry1Ca. In
      addition, reduction of ABBC2 and ABBC3 expression negatively affected some
      fitness components and induced up-regulation of arylphorin and repat5, genes that
      respond to Bt intoxication and that are found constitutively up-regulated in the
      Xen-R strain. CONCLUSIONS: The current results show the involvement of different
      members of the ABCC family in the mode of action of B. thuringiensis proteins and
      expand the role of the ABCC2 transporter in B. thuringiensis resistance beyond
      the Cry1A family of proteins to include Cry1Ca.

PMID- 24912446
TI  - Real-time navigation by fluorescence-based enhanced reality for precise
      estimation of future anastomotic site in digestive surgery.
AB  - BACKGROUND: Fluorescence-based enhanced reality (FLER) is a technique to evaluate
      intestinal perfusion based on the elaboration of the Indocyanine Green
      fluorescence signal. The aim of the study was to assess FLER's performances in
      evaluating perfusion in an animal model of long-lasting intestinal ischemia.
      MATERIALS AND METHODS: An ischemic segment was created in 18 small bowel loops in
      6 pigs. After 2 h (n = 6), 4 h (n = 6), and 6 h (n = 6), loops were evaluated
      clinically and by FLER to delineate five regions of interest (ROIs): ischemic
      zone (ROI 1), presumed viable margins (ROI 2a-2b), and vascularized areas (3a
      3b). Capillary lactates were measured to compare clinical vs. FLER assessment.
      Basal (V 0 ) and maximal (V max) mitochondrial respiration rates were determined
      according to FLER. RESULTS: Lactates (mmol/L) at clinically identified resection
      lines were significantly higher when compared to those identified by FLER (2.43
      +/- 0.95 vs. 1.55 +/- 0.33 p = 0.02) after 4 h of ischemia. Lactates at 2 h at
      ROI 1 were 5.45 +/- 2.44 vs. 1.9 +/- 0.6 (2a-2b; p < 0.0001) vs. 1.2 +/- 0.3 (3a
      3b; p < 0.0001). At 4 h, lactates were 4.36 +/- 1.32 (ROI 1) vs. 1.83 +/- 0.81
      (2a-2b; p < 0.0001) vs. 1.35 +/- 0.67 (3a-3b; p < 0.0001). At 6 h, lactates were
      4.16 +/- 2.55 vs. 1.8 +/- 1.2 vs. 1.45 +/- 0.83 at ROI 1 vs. 2a--2b (p = 0.013)
      vs. 3a-3b (p = 0.0035). Mean V 0 and V max (pmolO2/second/mg of tissue) were
      significantly impaired after 4 and 6 h at ROI 1 (V 0 (4h) = 34.83 +/- 10.39; V
      max (4h) = 76.6 +/- 29.09; V 0 (6h) = 44.1 +/- 12.37 and V max (6h) = 116.1 +/-
      40.1) when compared to 2a--2b (V 0 (4h) = 67.1 +/- 17.47 p = 0.00039; V max (4h)
      = 146.8 +/- 55.47 p = 0.0054; V 0 (6h) = 63.9 +/- 28.99 p = 0.03; V max (6h) =
      167.2 +/- 56.96 p = 0.01). V 0 and V max were significantly higher at 3a-3b.
      CONCLUSIONS: FLER may identify the future anastomotic site even after repetitive
      assessments and long-standing bowel ischemia.

PMID- 24912447
TI  - Activated delta-opioid receptors inhibit hydrogen peroxide-induced apoptosis in
      liver cancer cells through the PKC/ERK signaling pathway.
AB  - Apoptotic liver cancer cells have important roles in liver tumorigenesis and
      liver cancer progression. Recent studies have shown that delta-opioid receptors
      are highly expressed in human liver and liver cancer cells. The present study
      aimed to investigate the role of activated delta-opioid receptors on human liver
      cancer cell apoptosis and its interrelation with the mitochondria and the protein
      kinase C/extracellular-signal-regulated kinase (PKC/ERK) signaling pathway. H2O2
      was used to induce apoptosis in human liver cancer cells. During apoptosis,
      mitochondrial transmembrane potentials were observed to decrease, cytochrome c
      expression was found to increase and B cell lymphoma 2 (Bcl-2) expression
      decreased. These findings suggested that H2O2-induced apoptosis was mediated
      through the mitochondrial pathway. Of note, activated delta-opioid receptors were
      observed to inhibit H2O2-induced apoptosis in human liver cancer cells. Following
      delta-opioid receptor activation, the number of apoptotic liver cancer cells
      decreased, mitochondrial transmembrane potentials were restored, cytoplasmic
      cytochrome c and Bcl-2-associated X protein expression decreased and Bcl-2
      expression increased. These data suggested that delta-opioid receptor activation
      inhibited mitochondria-mediated apoptosis. In addition, activation of delta
      opioid receptors was observed to increase the expression of PKC and ERK in human
      liver cancer cells. Furthermore, upon inhibition of the PKC/ERK signaling
      pathway, the protective effect associated with the delta-opioid receptor on liver
      cancer cell apoptosis was inhibited, which was not associated with the status of
      delta-opioid receptor activation. These findings suggested that the PKC/ERK
      signaling pathway has an important role in delta-opioid receptor-mediated
      inhibition of apoptosis in human liver cancer cells. 

PMID- 24912448
TI  - Two-dimensional spectroscopic imaging with combined free induction decay and long
      TE acquisition (FID echo spectroscopic imaging, FIDESI) for the detection of
      intramyocellular lipids in calf muscle at 7 T.
AB  - The aim of this study was to introduce a two-dimensional chemical shift imaging
      (2D CSI) sequence, with simultaneous acquisition of free induction decay (FID)
      and long TEs, for the detection and quantification of intramyocellular lipids
      (IMCLs) in the calf at 7 T. The feasibility of the new 2D CSI sequence, which
      acquires FID (acquisition delay, 1.3 ms) and an echo (long TE) in one
      measurement, was evaluated in phantoms and volunteers (n = 5): TR/TE*/TE =
      800/1.3/156 ms; 48 * 48 matrix; field of view, 200 * 200 * 20 mm(3) ; Hamming
      filter; no water suppression; measurement time, 22 min 2 s. The IMCL
      concentration and subcutaneous lipid contamination were assessed. Spectra in the
      tibialis anterior (TA), gastrocnemius (GM) and soleus (SOL) muscles were
      analyzed. The water signal from the FID acquisition was used as an internal
      concentration reference. In the spectra from subcutaneous adipose tissue (SUB)
      and bone marrow (BM), an unsaturation index (UI) of the vinyl-H (5.3 ppm) to
      methyl-CH3 ratio, and a polyunsaturation index (pUI) of the diallylic-H (2.77
      ppm) to -CH3 ratio, were calculated. Long-TE spectra from muscles showed a
      simplified spectral pattern with well-separated IMCL for several muscle groups in
      the same scan. The IMCL to water ratio was largest in SOL (0.66% +/- 0.23%), and
      lower in GM (0.37% +/- 0.14%) and TA (0.36% +/- 0.12%). UI and pUI for SUB were
      0.65 +/- 0.06 and 0.18 +/- 0.04, respectively, and for BM were 0.60 +/- 0.16 and
      0.18 +/- 0.08, respectively. The new sequence, with the proposed name 'free
      induction decay echo spectroscopic imaging' (FIDESI), provides information on
      both specific lipid resonances and water signal from different tissues in the
      calf, with high spectral and spatial resolution, as well as minimal voxel
      bleeding and subcutaneous lipid contamination, in clinically acceptable
      measurement times.

PMID- 24912449
TI  - Hydrophobic interactions in donor-disulphide-acceptor (DSSA) probes looking
      beyond fluorescence resonance energy transfer theory.
AB  - Donor-linker-acceptor (DSSA) is a concept in fluorescence chemistry with acceptor
      being a fluorescent compound (FRET) or quencher. The DSSA probes used to measure
      thiol levels in vitro and in vivo. The reduction potential of these dyes are in
      the range of -0.60 V, much lower than the best thiol reductant reported in
      literature, the DTT (-0.33 V). DSSA disulphide having an unusually low reduction
      potential compared to the typical thiol reductants is a puzzle. Secondly, DSSA
      probes have a cyclized rhodamine ring as acceptor which does not have any
      spectral overlap with fluorescein, but quenches its absorbance and fluorescence.
      To understand the structural features of DSSA probes, we have synthesized DSSANa
      and DSSAOr. The calculated reduction potential of these dyes suggest that DSSA
      probes have an alternate mechanism from the FRET based quenching, namely
      hydrophobic interaction or dye to dye quenching. The standard reduction potential
      change with increasing complexity and steric hindrance of the molecule is small,
      suggesting that ultra- low Eo' has no contribution from the disulphide linker and
      is based on structural interactions between fluorescein and cyclized rhodamine.
      Our results help to understand the DSSA probe quenching mechanism and provide
      ways to design fluorescent probes.

PMID- 24912450
TI  - Highly sensitive visualization of inorganic mercury in mouse neurons using a
      fluorescent probe.
AB  - In the present study, we used the previously developed fluorescence probe, EPNP,
      to generate the first image of the distribution of mercuric ion in primary mouse
      neuron cultures. At postnatal day 1 (P1), the mice were intraperitoneally (IP)
      injected with mercuric chloride in doses ranging from 0.05 to 0.6 MUg/g body
      weight. After 1, 2, 3, and 4 days exposure, primary nervous cell cultures and
      frozen brain and spinal tissue sections were prepared and dyed using EPNP. On the
      third day of repeated injections, Hg(2+) was visualized in primary cerebral
      neuron cultures as an increase of Hg(2+)-induced fluorescence at the doses >= 0.1
      MUg/g. A similar accumulation of Hg(2+) was observed in frozen hippocampus tissue
      sections. In contrast, no Hg(2+) was observed in spinal cord neurons and spinal
      tissue sections. The detection of a low dose of IP injected mercury in mouse
      cerebral neurons facilitated the evaluation of the exposure risk to low-dose
      Hg(2+) in immature organisms. Moreover, the highly sensitive EPNP revealed Hg(2+)
      in the cerebral neurons of mice younger than P4, while the presence of Hg(2+) was
      not detected until >= P11 in previous reports. Thus, this technology and the
      results obtained herein are of interest for neurotoxicology.

PMID- 24912451
TI  - Synthesis, characterization and fluorescence studies of novel tetrachloroperylene
      azo hybrid dyes.
AB  - Novel rylene-azo hybrid dyes have been synthesized by condensation of azo-dyes
      with tetrachloroperylene dianhydride, possessing stupendous thermal, chemical and
      photochemical stability. Phenolic azo dyes are used for the nucleophilic
      replacement of chlorine substituents at 1,6,7,12-positions of perylene 3,4,9,10
      dianhydride system. The absorption maxima (y(max)) of these dyes have been
      determined in diverse solvents such as water, ethanol, methanol, ethyl acetate
      and N, N-dimethylformamide. Fluorescence spectra are taken in water and highest
      fluorescence was exhibited by dyes containing carboxylic groups. The y(max) and
      fluorescence of these dyes is greatly affected by polarity of solvents. The
      structures of newly synthesized rylene-azo hybrid dyes have been confirmed by UV,
      FTIR and (1)HNMR spectroscopy.

PMID- 24912452
TI  - High-resolution dynamic speech imaging with joint low-rank and sparsity
      constraints.
AB  - PURPOSE: To enable dynamic speech imaging with high spatiotemporal resolution and
      full-vocal-tract spatial coverage, leveraging recent advances in sparse sampling.
      METHODS: An imaging method is developed to enable high-speed dynamic speech
      imaging exploiting low-rank and sparsity of the dynamic images of articulatory
      motion during speech. The proposed method includes: (a) a novel data acquisition
      strategy that collects spiral navigators with high temporal frame rate and (b) an
      image reconstruction method that derives temporal subspaces from navigators and
      reconstructs high-resolution images from sparsely sampled data with joint low
      rank and sparsity constraints. RESULTS: The proposed method has been
      systematically evaluated and validated through several dynamic speech
      experiments. A nominal imaging speed of 102 frames per second (fps) was achieved
      for a single-slice imaging protocol with a spatial resolution of 2.2 * 2.2 * 6.5
      mm(3) . An eight-slice imaging protocol covering the entire vocal tract achieved
      a nominal imaging speed of 12.8 fps with the identical spatial resolution. The
      effectiveness of the proposed method and its practical utility was also
      demonstrated in a phonetic investigation. CONCLUSION: High spatiotemporal
      resolution with full-vocal-tract spatial coverage can be achieved for dynamic
      speech imaging experiments with low-rank and sparsity constraints.

PMID- 24912453
TI  - Dry needling for management of pain in the upper quarter and craniofacial region.
AB  - Dry needling is a therapeutic intervention that has been growing in popularity.
      It is primarily used with patients that have pain of myofascial origin. This
      review provides background about dry needling, myofascial pain, and craniofacial
      pain. We summarize the evidence regarding the effectiveness of dry needling. For
      patients with upper quarter myofascial pain, a 2013 systematic review and meta
      analysis of 12 randomized controlled studies reported that dry needling is
      effective in reducing pain (especially immediately after treatment) in patients
      with upper quarter pain. There have been fewer studies of patients with
      craniofacial pain and myofascial pain in other regions, but most of these studies
      report findings to suggest the dry needling may be helpful in reducing pain and
      improving other pain related variables such as the pain pressure threshold. More
      rigorous randomized controlled trials are clearly needed to more fully elucidate
      the effectiveness of dry needling. 

PMID- 24912455
TI  - 3D networked graphene-ferromagnetic hybrids for fast shape memory polymers with
      enhanced mechanical stiffness and thermal conductivity.
AB  - A novel 3D networked graphene-ferromagnetic hybrid can be easily fabricated using
      one-step microwave irradiation. By incorporating this hybrid material into shape
      memory polymers, the synergistic effects of fast speed and the enhancement of
      thermal conductivity and mechanical stiffness can be achieved. This can be
      broadly applicable to designing magneto-responsive shape memory polymers for
      multifunction applications. 

PMID- 24912454
TI  - Colony morphology and transcriptome profiling of Pseudomonas putida KT2440 and
      its mutants deficient in alginate or all EPS synthesis under controlled matric
      potentials.
AB  - Pseudomonas putida is a versatile bacterial species adapted to soil and its
      fluctuations. Like many other species living in soil, P. putida often faces water
      limitation. Alginate, an exopolysaccharide (EPS) produced by P. putida, is known
      to create hydrated environments and alleviate the effect of water limitation. In
      addition to alginate, P. putida is capable of producing cellulose (bcs), putida
      exopolysaccharide a (pea), and putida exopolysaccharide b (peb). However, unlike
      alginate, not much is known about their roles under water limitation. Hence, in
      this study we examined the role of different EPS components under mild water
      limitation. To create environmentally realistic water limited conditions as
      observed in soil, we used the Pressurized Porous Surface Model. Our main
      hypothesis was that under water limitation and in the absence of alginate other
      exopolysaccharides would be more active to maintain homeostasis. To test our
      hypothesis, we investigated colony morphologies and whole genome transcriptomes
      of P. putida KT2440 wild type and its mutants deficient in synthesis of either
      alginate or all known EPS. Overall our results support that alginate is an
      important exopolysaccharide under water limitation and in the absence of alginate
      other tolerance mechanisms are activated. 

PMID- 24912456
TI  - The addition of STEPPS in the treatment of patients with bipolar disorder and
      comorbid borderline personality features: a protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Bipolar disorder (BD) and borderline personality disorder (BPD) both
      are severe and chronic psychiatric disorders. Both disorders have overlapping
      symptoms, and current research shows that the presence of a BPD has an adverse
      effect on the course of BD. The limited research available shows an unfavorable
      illness course, a worse prognosis and response to medication, longer treatment
      duration, more frequent psychiatric admissions, higher drop-out, increased risk
      of substance abuse, increased risk of suicide, and more impairment of social and
      occupational functioning. However, there is no research available on the effect
      of specific psychotherapeutic treatment for this patients. METHODS/DESIGN: This
      paper presents the protocol of a RCT to investigate the presence of borderline
      personality features in patients treated for BD (study part 1) and the
      effectiveness of STEPPS (Systems Training for Emotional Predictability and
      Problem Solving) added to treatment as usual (TAU) for BD compared to TAU in
      patients with BD and comorbid borderline personality features (study part 2).
      STEPPS is a validated and effective intervention for BPD. The study population
      consists of patients treated for BD at specialized outpatient clinics for BD in
      the Netherlands. At first the prevalence of comorbid borderline personality
      features in outpatients with BD is investigated. Inclusion criteria for study
      part 2 is defined as having three or more of the DSM-IV-TR diagnostic criteria of
      BPD, including impulsivity and anger bursts. Primary outcomes will be the
      frequency and severity of manic and depressive recurrences as well as severity,
      course and burden of borderline personality features. Secondary outcomes will be
      quality of life, utilizing mental healthcare and psychopathologic symptoms not
      primarily related to BD or BPD. Assessment will be at baseline, at the end of the
      intervention, and at 12 and 18 months follow-up. DISCUSSION: This will be the
      first randomized controlled trial of a specific intervention in patients with BD
      and comorbid BPD or borderline personality features. There are no recommendations
      in the guideline of treatment of bipolar disorders for patients with this complex
      comorbidity. We expect that a combined treatment aimed at mood disorder and
      emotion regulation will improve treatment outcomes for these patients.

PMID- 24912457
TI  - Secular trend of dental development in Dutch children.
AB  - Many studies have established dental age standards for different populations;
      however, very few studies have investigated whether dental development is stable
      over time on a population level. Therefore, the aim of this study was to analyze
      changes in dental maturity in Dutch children born between 1961 and 2004. We used
      2,655 dental panoramic radiographs of 2- to 16-year-old Dutch children from
      studies performed in three major cities in the Netherlands. Based on a trend in
      children born between 1961 and 1994, we predicted that a child of a certain age
      and gender born in 1963 achieved the same dental maturity on average, 1.5 years
      later than a child of the same age born 40 years later. After adjusting for the
      birth year of a child in the analysis, the regression coefficient of the city
      variable was reduced by 56.6% and it remained statistically significant. The
      observed trend from 1961 to 1994 was extrapolated to 9- to 10-year-old children
      born in 2002-2004, and validation with the other samples of children with the
      same characteristics showed that 95.9%-96.8% of the children had dental maturity
      within the 95% of the predicted range. Dental maturity score was significantly
      and positively associated with the year of birth, gender, and age in Dutch
      children, indicating a trend in earlier dental development during the observation
      period, 1961-2004. These findings highlight the necessity of taking the year of
      birth into account when assessing dental development within a population with a
      wider time span.

PMID- 24912458
TI  - Torque density measurements on vortex fluids produced by symmetry-breaking
      rational magnetic fields.
AB  - We have recently reported on the discovery that an infinite class of triaxial
      magnetic fields is capable of producing rotational flows in magnetic particle
      suspensions. These triaxial fields are created by applying a dc field
      orthogonally to a rational biaxial field, comprised of orthogonal components
      whose frequencies form a rational ratio. The vorticity axis can be parallel to
      any of the three field components and can be predicted by a careful consideration
      of the symmetry of the dynamic field. In this paper we not only test the field
      symmetry predictions, but also quantify fluid vorticity as a function of the
      field parameters (strength, frequency ratio, phase angle and relative dc field
      strength) and particle shape. These measurements validate the symmetry
      predictions and demonstrate that rational fields are as effective as vortex
      fields for producing strong fluid mixing, yet have the advantage that small
      changes in the frequency of one of the field components can change the vorticity
      axis. This approach extends the possibilities for noncontact control of fluid
      flows and should be useful in areas such as microfluidics, and the manipulation
      and mixing of microdroplets. 

PMID- 24912459
TI  - A pilot randomized trial of an online parenting skills program for pediatric
      traumatic brain injury: improvements in parenting and child behavior.
AB  - This pilot study examined changes in parenting skills and child behavior
      following participation in an online positive parenting skills program designed
      for young children with traumatic brain injury (TBI). Thirty-seven families with
      a child between 3 and 9 years of age who sustained a moderate to severe TBI were
      randomly assigned to one of two interventions: online parenting skills training
      (n=20) or access to Internet resources on managing brain injury (n=17). Parent
      child interaction observations and parent ratings of child behavior were
      collected pre- and post-treatment. Generalized estimating equations and mixed
      models were used to examine changes in parenting skills and child behavior
      problems as well as the moderating role of family income on treatment response.
      Participants in the parenting skills group displayed significant improvements in
      observed positive parenting skills relative to participants in the Internet
      resource group. Income moderated improvements in parent ratings of child
      behavior, with participants in the low-income parenting skills group and high
      income Internet resource group reporting the greatest improvements in behavior.
      This is the first randomized controlled trial examining online parenting skills
      training for families of young children with TBI. Improvements in positive
      parenting skills and child behavior support the utility of this intervention,
      particularly for families from lower socioeconomic backgrounds.

PMID- 24912460
TI  - Specificity of disgust domains in the prediction of contamination anxiety and
      avoidance: a multimodal examination.
AB  - Although core, animal-reminder, and contamination disgust are viewed as distinct
      "types" of disgust vulnerabilities, the extent to which individual differences in
      the three disgust domains uniquely predict contamination-related anxiety and
      avoidance remains unclear. Three studies were conducted to fill this important
      gap in the literature. Study 1 was conducted to first determine if the three
      types of disgust could be replicated in a larger and more heterogeneous sample.
      Confirmatory factor analysis revealed that a bifactor model consisting of a
      "general disgust" dimension and the three distinct disgust dimensions yielded a
      better fit than a one-factor model. Structural equation modeling in Study 2
      showed that while latent core, animal-reminder, and contamination disgust factors
      each uniquely predicted a latent "contamination anxiety" factor above and beyond
      general disgust, only animal-reminder uniquely predicted a latent "non
      contamination anxiety" factor above and beyond general disgust. However, Study 3
      found that only contamination disgust uniquely predicted behavioral avoidance in
      a public restroom where contamination concerns are salient. These findings
      suggest that although the three disgust domains are associated with contamination
      anxiety and avoidance, individual differences in contamination disgust
      sensitivity appear to be most uniquely predictive of contamination-related
      distress. The implications of these findings for the development and maintenance
      of anxiety-related disorders marked by excessive contamination concerns are
      discussed. 

PMID- 24912461
TI  - Examination of the core cognitive components of cognitive behavioral therapy and
      acceptance and commitment therapy: an analogue investigation.
AB  - We aimed to examine the core elements of cognitive behavioral therapy and
      acceptance and commitment therapy that target distressing negative cognitions,
      cognitive restructuring (CR) and cognitive defusion (CD), respectively.
      Participants (N=142) recalled a saddening autobiographical event, identified a
      distressing thought it triggered, and completed a task that induced rumination on
      these cognitions. They then completed one of four brief interventions that
      targeted these emotionally charged cognitions: analogue versions of CR and CD,
      and two control interventions. The personal negative cognitions were then
      reactivated to examine the protective effects of these interventions. CR and CD
      were similarly efficacious in alleviating distress, compared to a control
      intervention that focused on participants' negative thoughts. Mood improvement
      was associated with state levels of reappraisal and not with acceptance in CR,
      whereas the reverse was observed in CD. Improvement was associated with perceived
      efficacy of the intervention in CR but not in CD. The present findings suggest
      that although CR and CD effectively promote different types of cognitive
      strategies, they may share important features that set them both apart from
      maladaptive forms of coping. 

PMID- 24912462
TI  - Combined medication and CBT for generalized anxiety disorder with African
      American participants: reliability and validity of assessments and preliminary
      outcomes.
AB  - Using data from a study of combined cognitive behavioral therapy (CBT) and
      venlafaxine XR in the treatment of generalized anxiety disorder (GAD), the
      current article examines the reliability and convergent validity of scales, and
      preliminary outcomes, for African American compared with European American
      patients. Internal consistency and short-term stability coefficients for African
      Americans (n=42) were adequate and similar or higher compared with those found
      for European Americans (n=164) for standard scales used in GAD treatment
      research. Correlations among outcome measures among African Americans were in
      general not significantly different for African Americans compared with European
      Americans. A subset of patients with DSM-IV-diagnosed GAD (n=24 African
      Americans; n=52 European Americans) were randomly selected to be offered the
      option of adding 12 sessions of CBT to venlafaxine XR treatment. Of those offered
      CBT, 33.3% (n=8) of the African Americans and 32.6% (n=17) of the European
      Americans accepted and attended at least one CBT treatment session. The outcomes
      for African Americans receiving combined treatment were not significantly
      different from European Americans receiving combined treatment on primary or
      secondary efficacy measures. 

PMID- 24912463
TI  - The effect of support on internet-delivered treatment for insomnia: does baseline
      depression severity matter?
AB  - Internet-delivered cognitive-behavioral treatment is effective for insomnia.
      However, little is known about the beneficial effects of support. Recently we
      demonstrated that motivational support moderately improved the effects of
      Internet-delivered treatment for insomnia. In the present study, we tested
      whether depressive symptoms at baseline moderate the effect of support on
      Internet-delivered treatment for insomnia. We performed a multilevel intention-to
      treat analysis on 262 participants in a randomized controlled trial. We found
      that baseline depressive symptoms moderated the effect of support on sleep
      efficiency, total sleep time, and sleep onset latency (but not on wake after
      sleep onset, number of nightly awakenings, or the Insomnia Severity Index). This
      means that for these variables, people with high levels of depressive symptoms
      benefit from support, whereas people with low levels of depressive symptoms
      improve regardless of support. The data show that baseline depression severity
      plays an important role in the way Internet treatments need to be delivered.
      These findings open up opportunities to personalize the support offered in
      Internet-delivered treatments. 

PMID- 24912464
TI  - An experimental test of the effects of parental modeling on panic-relevant escape
      and avoidance among early adolescents.
AB  - Escape and avoidance behaviors play a prominent role in the maintenance and
      possibly development of panic disorder, yet the literature regarding the etiology
      of these emotion-regulation strategies is relatively underdeveloped. The current
      study experimentally tests hypotheses that parental modeling of escape during a
      well-established panic-relevant biological challenge increases panic-relevant
      escape and avoidance among offspring. Fifty physically and psychologically
      healthy early adolescents (28 females; Mage=11.58; 86% Caucasian), stratified by
      gender, were randomly assigned to observe one of their parents (39 females;
      Mage=40.04): either (a) model completing a 3-min voluntary hyperventilation
      exercise (no escape modeling group) or (b) model premature termination of a
      similar procedure (escape modeling group). Offspring in the escape modeling group
      demonstrated a stronger escape response by discontinuing their own challenge
      sooner than those in the no-escape modeling group (r=.70). No group differences
      emerged in terms of avoidance responding, as indexed by nearly identical
      responding in terms of delay time before initiating the challenge, respiration
      rate, and self-reported willingness to engage in a second proposed challenge.
      Results suggest that parental behaviors may play an important role in the
      development of some forms of panic-relevant responding. These preliminary
      findings may have important implications for future prevention programs targeting
      parents and at-risk youth. 

PMID- 24912465
TI  - Theory of mind impairments in social anxiety disorder.
AB  - Social anxiety disorder (SAD) is a common psychiatric disorder characterized by a
      persistent, excessive fear and avoidance of social and performance situations.
      Research on cognitive biases indicates individuals with SAD may lack an accurate
      view of how they are perceived by others, especially in social situations when
      they allocate important attentional resources to monitoring their own actions as
      well as external threat. In the present study, we explored whether socially
      anxious individuals also have impairments in theory of mind (ToM), or the ability
      to comprehend others' mental states, including emotions, beliefs, and intentions.
      Forty socially anxious and 40 non-socially-anxious comparison participants
      completed two ToM tasks: the Reading the Mind in the Eyes and the Movie for the
      Assessment of Social Cognition. Participants with SAD performed worse on ToM
      tasks than did non-socially-anxious participants. Relative to comparison
      participants, those with SAD were more likely to attribute more intense emotions
      and greater meaning to what others were thinking and feeling. These group
      differences were not due to interpretation bias. The ToM impairments in people
      with SAD are in the opposite direction of those in people with autism spectrum
      conditions whose inferences about the mental states of other people are absent or
      very limited. This association between SAD and ToM may have important
      implications for our understanding of both the maintenance and treatment of
      social anxiety disorder. 

PMID- 24912466
TI  - Assessing treatment integrity in cognitive-behavioral therapy: comparing session
      segments with entire sessions.
AB  - The evaluation of treatment integrity (therapist adherence and competence) is a
      necessary condition to ensure the internal and external validity of psychotherapy
      research. However, the evaluation process is associated with high costs, because
      therapy sessions must be rated by experienced clinicians. It is debatable whether
      rating session segments is an adequate alternative to rating entire sessions.
      Four judges evaluated treatment integrity (i.e., therapist adherence and
      competence) in 84 randomly selected videotapes of cognitive-behavioral therapy
      for major depressive disorder, social anxiety disorder, and hypochondriasis (from
      three different treatment outcome studies). In each case, two judges provided
      ratings based on entire therapy sessions and two on session segments only (i.e.,
      the middle third of the entire sessions). Interrater reliability of adherence and
      competence evaluations proved satisfactory for ratings based on segments and the
      level of reliability did not differ from ratings based on entire sessions.
      Ratings of treatment integrity that were based on entire sessions and session
      segments were strongly correlated (r=.62 for adherence and r=.73 for competence).
      The relationship between treatment integrity and outcome was comparable for
      ratings based on session segments and those based on entire sessions. However,
      significant relationships between therapist competence and therapy outcome were
      only found in the treatment of social anxiety disorder. Ratings based on segments
      proved to be adequate for the evaluation of treatment integrity. The findings
      demonstrate that session segments are an adequate and cost-effective alternative
      to entire sessions for the evaluation of therapist adherence and competence. 

PMID- 24912467
TI  - If I only knew why: the relationship between brooding, beliefs about rumination,
      and perceptions of treatments.
AB  - People who tend to engage in brooding, the maladaptive subtype of rumination, are
      at risk to develop depression. Brooders often endorse metacognitive beliefs that
      self-focused ruminative thinking is beneficial. In the current study, we examined
      whether brooding and positive beliefs about rumination are associated with
      perceptions of and preferences for treatments for depression. Participants
      (N=118) read descriptions of two different clusters of treatments for depression,
      Insight-Oriented (IO) treatments and Activation-Oriented (AO) treatments. They
      then rated treatment efficacy and credibility and completed self-report measures
      of rumination (including brooding and reflection subscales), beliefs about
      rumination, and depression. Brooding and metacognitive positive beliefs about
      rumination were associated with positive perceptions of IO (but not AO)
      treatments. Positive beliefs about rumination contributed to the prediction of
      perceptions of IO treatments (but not AO treatments) beyond the effect of
      brooding. We discuss the implications of these findings for individuals' decision
      making processes regarding which type of treatment to seek. 

PMID- 24912468
TI  - Perceived criticism and marital adjustment predict depressive symptoms in a
      community sample.
AB  - Depressive symptoms are related to a host of negative individual and family
      outcomes; therefore, it is important to establish risk factors for depressive
      symptoms to design prevention efforts. Following studies in the marital and
      psychiatric literatures regarding marital factors associated with depression, we
      tested two potential predictors of depressive symptoms: marital adjustment and
      perceived spousal criticism. We assessed 249 spouses from 132 married couples
      from the community during their first year of marriage and at three time points
      over the next 10 years. Initial marital adjustment significantly predicted
      depressive symptoms for husbands and wives at all follow-ups. Further, perceived
      criticism significantly predicted depressive symptoms at the 5- and 10-year
      follow-ups. However, at the 1-year follow-up, this association was significant
      for men but not for women. Finally, a model where the contributions of marital
      adjustment and perceived criticism were tested together suggested that both play
      independent roles in predicting future depressive symptoms. These findings
      highlight the potential importance of increasing marital adjustment and reducing
      perceived criticism at the outset of marriage as a way to reduce depressive
      symptoms during the course of marriage.

PMID- 24912469
TI  - Toward a cognitive-behavioral classification system for mental disorders.
AB  - As is true for its predecessors, the recently published DSM-5 uses arbitrary
      criteria and cutoffs to define categories of mental disorders that are of
      questionable validity and that provide no guidance for treatment. Recently, the
      NIMH introduced an alternative classification system, the Research Domain
      Criteria (RDoC). Both the DSM-5 and the RDoC initiative make the strong
      assumption that psychological problems are expressions of specific latent disease
      entities. In contrast, the complex causal network approach conceptualizes
      psychological problems as mutually interacting, often reciprocally reinforcing,
      elements of a complex causal network. The cognitive behavioral model offers a
      classification framework that is compatible with the complex causal network
      approach and provides a treatment-relevant alternative to the latent disease
      model that is the basis for the DSM-5 and the RDoC initiative. 

PMID- 24912471
TI  - MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits
      in relapsing-remitting multiple sclerosis.
AB  - Despite that cognitive impairment is a known early feature present in multiple
      sclerosis (MS) patients, the biological substrate of cognitive deficits in MS
      remains elusive. In this study, we assessed whether T1 relaxometry, as obtained
      in clinically acceptable scan times by the recent Magnetization Prepared 2 Rapid
      Acquisition Gradient Echoes (MP2RAGE) sequence, may help identifying the
      structural correlate of cognitive deficits in relapsing-remitting MS patients
      (RRMS). Twenty-nine healthy controls (HC) and forty-nine RRMS patients underwent
      high-resolution 3T magnetic resonance imaging to obtain optimal cortical lesion
      (CL) and white matter lesion (WML) count/volume and T1 relaxation times. T1 z
      scores were then obtained between T1 relaxation times in lesion and the
      corresponding HC tissue. Patient cognitive performance was tested using the Brief
      Repeatable Battery of Neuro-psychological Tests. Multivariate analysis was
      applied to assess the contribution of MRI variables (T1 z scores, lesion
      count/volume) to cognition in patients and Bonferroni correction was applied for
      multiple comparison. T1 z scores were higher in WML (p < 0.001) and CL-I (p <
      0.01) than in the corresponding normal-appearing tissue in patients, indicating
      relative microstructural loss. (1) T1 z scores in CL-I (p = 0.01) and the number
      of CL-II (p = 0.04) were predictors of long-term memory; (2) T1 z scores in CL-I
      (beta = 0.3; p = 0.03) were independent determinants of long-term memory storage,
      and (3) lesion volume did not significantly influenced cognitive performances in
      patients. Our study supports evidence that T1 relaxometry from MP2RAGE provides
      information about microstructural properties in CL and WML and improves
      correlation with cognition in RRMS patients, compared to conventional measures of
      disease burden.

PMID- 24912470
TI  - How predictors and patterns of stroke recurrence after a TIA differ during the
      first year of follow-up.
AB  - The highest risk of subsequent stroke after a TIA occurs within the first week
      after the index event. However, the risk of stroke recurrence (SR) remains high
      during the first year of follow-up. We studied the temporal pattern and
      predictors of SR (at 7 days and from 7 days to 1-year follow-up). Between April
      2008 and December 2009, we included 1,255 consecutive TIA patients from 30
      Spanish stroke centers (PROMAPA study). We determined the short-term (at 7 days)
      and long-term (from 8 days to 1 year) risk of SR. Patients who underwent short
      term recurrence and long-term recurrence were compared with regard to clinical
      findings, vascular territories, and etiology. Enough information (clinical
      variables and extracranial vascular imaging) was assessed in 1,137 (90.6 %)
      patients. The 7-day stroke risk was 2.6 %. 32 (3.0 %) patients had an SR after 7
      day follow-up. Multiple TIA (HR 3.50, 1.67-7.35, p = 0.001) and large artery
      atherosclerosis (HR 2.51, 1.17-5.37, p = 0.018) were independent predictors of
      early SR, whereas previous stroke (HR 1.40, 1.03-1.92, p = 0.034) and coronary
      heart disease (2.65, 1.28-5.50, p = 0.009) were independent predictors of late
      SR. Notoriously, 80 % of SR happened in the same territory of the index TIA at 7
      day follow-up, whereas only 38 % during the long-term follow-up (p < 0.001).
      Different predictors of SR were identified throughout the follow-up period.
      Moreover, the ischemic mechanism differed in early and late stroke recurrences.

PMID- 24912472
TI  - Surgical technique of hepatectomy combined with simultaneous resection of hepatic
      artery and portal vein for perihilar cholangiocarcinoma (with video).
AB  - Perihilar cholangiocarcinomas often involve the bifurcation of the portal vein
      and the hepatic artery at initial presentation. Previously, vascular invasion was
      a major obstacle for R0 resection; therefore, such tumors were regarded as
      locally advanced, unresectable disease. Recently, in leading centers, these
      tumors have been resected using a specific technique, vascular resection and
      reconstruction. Vascular resection is classified into three types: portal vein
      resection alone, hepatic artery resection alone, and simultaneous resection of
      both the portal vein and hepatic artery. Of these, portal vein resection is
      widely performed, whereas hepatic artery resection remains controversial.
      Therefore, hepatectomy combined with simultaneous resection of the portal vein
      and hepatic artery represents one of the most complicated and challenging
      procedures in hepatobiliary surgery. The survival benefit of this extended
      procedure remains unproven, and there is only a single study reporting an
      unexpectedly favorable outcome in 50 patients. Considering the dismal survival in
      patients with unresectable disease, hepatic artery resection and/or portal vein
      resection may be a promising option of choice. However, the technique is highly
      demanding and has not been standardized. Therefore, this extended surgery may be
      allowed only in selected hepatobiliary centers. 

PMID- 24912474
TI  - Two cases of concomitant diffuse large B-cell lymphoma and myelodysplastic
      syndrome.

PMID- 24912473
TI  - Hypoxia-targeted triple suicide gene therapy radiosensitizes human colorectal
      cancer cells.
AB  - The hypoxic microenvironment, an important feature of human solid tumors but
      absent in normal tissue, may provide an opportunity for cancer-specific gene
      therapy. The purpose of the present study was to investigate whether hypoxia
      driven triple suicide gene TK/CD/UPRT expression enhances cytotoxicity to
      ganciclovir (GCV) and 5-fluorocytosine (5-FC), and sensitizes human colorectal
      cancer to radiation in vitro and in vivo. Stable transfectant of human colorectal
      HCT8 cells was established which expressed hypoxia-inducible vectors (HRE-TK/eGFP
      and HRE-CD/UPRT/mDsRed). Hypoxia-induced expression/function of TK, CD and UPRT
      was verified by western blot analysis, flow cytometry, fluorescent microscopy and
      cytotoxicity assay of GCV and 5-FC. Significant radiosensitization effects were
      detected after 5-FC and GCV treatments under hypoxic conditions. In the tumor
      xenografts, the distribution of TK/eGFP and CD/UPRT/mDsRed expression visualized
      with fluorescence microscopy was co-localized with the hypoxia marker
      pimonidazole positive staining cells. Furthermore, administration of 5-FC and GCV
      in mice in combination with local irradiation resulted in tumor regression, as
      compared with prodrug or radiation treatments alone. Our data suggest that the
      hypoxia-inducible TK/GCV+CDUPRT/5-FC triple suicide gene therapy may have the
      ability to specifically target hypoxic cancer cells and significantly improve the
      tumor control in combination with radiotherapy.

PMID- 24912475
TI  - Long-term follow-up of stereotactic radiosurgery for head and neck malignancies.
AB  - BACKGROUND: Stereotactic radiosurgery is widely applied to deliver additional
      dose to head and neck tumors. However, its safety and efficacy remains equivocal.
      METHODS: One hundred eighty-four patients with primary head and neck cancers
      treated between January 1990 and August 2012 with Gamma Knife stereotactic
      radiosurgery were retrospectively reviewed. RESULTS: Two hundred fifteen sites
      were treated with Gamma Knife stereotactic radiosurgery among 184 patients. Fifty
      one percent of patients received concurrent external beam radiotherapy (EBRT),
      72% had prior surgery, and 46% received chemotherapy. Most (44%) had squamous
      cell carcinoma and most patients (65%) were treated for recurrent disease. With a
      median follow-up of 17.3 months, 12-month local control was 82%. Late effects
      occurred in 59 patients with the most common being temporal lobe necrosis (15
      patients). CONCLUSION: Radiosurgery can provide tumor control for patients with
      head and neck cancers involving the skull base. Long-term follow-up is important
      in survivors to identify late effects.

PMID- 24912476
TI  - The role of exercise training on lipoprotein profiles in adolescent males.
AB  - BACKGROUND: Major cardiovascular disorders are being recognized earlier in life.
      In this study we examined the effects of swimming and soccer training on male
      adolescent lipid-lipoprotein profiles relative to a maturity matched control
      group to determine the effects of these exercises on specific cardiovascular risk
      and anti-risk factors. METHODS: Forty five adolescent males (11.81 +/- 1.38 yr)
      including swimmers (SW), soccer players (SO), and non-athlete, physically active
      individuals as controls (C), participated in this study. Training groups
      completed 12-wk exercise programs on three non-consecutive days per week. Plasma
      low-density lipoprotein (LDL), very low density lipoprotein (VLDL), high density
      lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), total
      cholesterol (TC), and triglyceride (TG) levels were measured in control, pre
      training, during-training, and post-training. RESULTS: In response to the 12-wk
      training period, the SO group demonstrated a decrease in the mean LDL level
      compared to the SW and C (SW: 0.15%; SO: -9.51%; C: 19.59%; p < 0.001) groups.
      There was an increase in both the SW and SO groups vs. the control in mean HDL
      (SW: 5.66%; SO: 3.07%; C: -7.21%; p < 0.05) and apoA-I (SW: 3.86%; SO: 5.48%; C: 
      1.01%; p < 0.05). ApoB was considerably lower in the training groups vs. control
      (SW: -9.52%; SO: -13.87%; C: 21.09%; p < 0.05). ApoA-I/apoB ratio was
      significantly higher in training groups vs. control (SW: 16.74%; SO: 23.71%; C: 
      17.35%; p < 0.001). There were no significant differences between groups for
      other factors. CONCLUSIONS: The favorable alterations in LDL, HDL, apoA-I, and
      apoB observed in the training groups suggest that both regular swimming or soccer
      exercise can potentially mitigate cardiovascular risk in adolescent males.

PMID- 24912477
TI  - Exome sequencing of hepatoblastoma reveals novel mutations and cancer genes in
      the Wnt pathway and ubiquitin ligase complex.
AB  - Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations
      in the beta-catenin gene that lead to constitutive activation of the Wnt pathway
      have been detected in a large proportion of HB tumors. To identify novel
      mutations in HB, we performed whole-exome sequencing of six paired HB tumors and
      their corresponding lymphocytes. This identified 24 somatic nonsynonymous
      mutations in 21 genes, many of which were novel, including three novel mutations
      targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway,
      and genes previously shown to be involved in the ubiquitin ligase complex (SPOP,
      KLHL22, TRPC4AP, and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2
      (R968H/S969C) were observed to be gain-of-functional mutations, and the CAPRIN2
      (R968H/S969C) was also shown to activate the Wnt pathway in HB cells. These
      findings suggested the activation of the Wnt pathway in HB, which was confirmed
      by immunohistochemical staining of the beta-catenin in 42 HB tumors. We further
      used short hairpin RNA (shRNA)-mediated interference to assess the effect of 21
      mutated genes on HB cell survival. The results suggested that one novel oncogene
      (CAPRIN2) and three tumor suppressors (SPOP, OR5I1, and CDC20B) influence HB cell
      growth. Moreover, we found that SPOP S119N is a loss-of-function mutation in HB
      cells. We finally demonstrated that one of the mechanisms by which SPOP inhibits
      HB cell proliferation is through regulating CDKN2B expression. CONCLUSION: These
      results extend the landscape of genetic alterations in HB and highlight the
      dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis.

PMID- 24912479
TI  - Location, location, location: what can geographic information science (GIS) offer
      sexual health research?

PMID- 24912478
TI  - Antioxidant and neurotoxicity markers in the model organism Enchytraeus albidus
      (Oligochaeta): mechanisms of response to atrazine, dimethoate and carbendazim.
AB  - The present study aimed to investigate the effects of dimethoate, atrazine and
      carbendazim on the antioxidant defences and neuronal function of the soil
      organism Enchytraeus albidus. Effects were studied at concentrations known to
      affect their reproduction (EC20, EC50 and EC90) and along time (2, 4, 8, 14 and
      21 days). In general, responses were more pronounced at periods of exposure
      longer than 8 days and at the highest concentrations. Multivariate statistics
      (RDA-PRC) clearly displayed that exposure duration had an effect itself,
      biomarkers' responses showed interaction for all pesticides and catalase scored
      consistently high, indicating its relevancy in the group of measured markers.
      Univariate analysis indicated oxidative stress for all pesticides and atrazine
      induced oxidative damage in lipids. Atrazine seems to be effectively metabolized
      by GST of the biotransformation system, as its activity significantly increased
      after exposure to this pesticide. Dimethoate caused ChE inhibition, indicating an
      impairment of the neuronal function. Carbendazim impaired the antioxidant system,
      but no oxidative damage was observed, along with any effects on the ChE activity.
      The integrated biomarker response analysis was performed but we suggest
      modifications due to limiting artefacts.

PMID- 24912480
TI  - An update on the medical management of breast cancer.

PMID- 24912481
TI  - A 1536-well fluorescence polarization assay to screen for modulators of the
      MUSASHI family of RNA-binding proteins.
AB  - RNA-binding proteins (RBPs) can act as stem cell modulators and oncogenic
      drivers, but have been largely ignored by the pharmaceutical industry as
      potential therapeutic targets for cancer. The MUSASHI (MSI) family has recently
      been demonstrated to be an attractive clinical target in the most aggressive
      cancers. Therefore, the discovery and development of small molecule inhibitors
      could provide a novel therapeutic strategy. In order to find novel compounds with
      MSI RNA binding inhibitory activity, we have developed a fluorescence
      polarization (FP) assay and optimized it for high throughput screening (HTS) in a
      1536-well microtiter plate format. Using a chemical library of 6,208 compounds,
      we performed pilot screens, against both MSI1 and MSI2, leading to the
      identification of 7 molecules for MSI1, 15 for MSI2 and 5 that inhibited both. A
      secondary FP dose-response screen validated 3 MSI inhibitors with IC50 below 10
      MUM. Out of the 25 compounds retested in the secondary screen only 8 demonstrated
      optical interference due to high fluorescence. Utilizing a SYBR-based RNA
      electrophoresis mobility shift assay (EMSA), we further verified MSI inhibition
      of the top 3 compounds. Surprisingly, even though several aminoglycosides were
      present in the library, they failed to demonstrate MSI inhibitor activity
      challenging the concept that these compounds are pan-active against RBPs. In
      summary, we have developed an in vitro strategy to identify MSI specific
      inhibitors using an FP HTS platform, which will facilitate novel drug discovery
      for this class of RBPs. 

PMID- 24912482
TI  - Hsp70--a biomarker for tumor detection and monitoring of outcome of radiation
      therapy in patients with squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Tumor but not normal cells frequently overexpress heat shock protein
      70 (Hsp70) and present it on their cell surface (mHsp70) from where it can be
      actively released. Therefore, membrane (mHsp70) and soluble Hsp70 (sHsp70) were
      investigated as potential tumor biomarkers and for monitoring the outcome of
      radiation therapy. METHODS: Biopsies and blood were collected from patients with
      squamous cell carcinoma of the head and neck (SCCHN) at different time points
      (before, during therapy and in the follow-up period). Hsp70 membrane expression
      was determined on single cell suspensions of tumor biopsies and reference tissues
      by flow cytometry, sHsp70 protein and antibody levels were determined in the
      serum of patients and healthy donors by ELISA and NK cell markers that are
      related to the presence of sHsp70 were analyzed in the patient's peripheral blood
      lymphocytes (PBL). RESULTS: Tumor biopsies exhibited significantly increased
      mHsp70 expression levels compared to the reference tissue. Soluble Hsp70 levels
      were significantly higher in SCCHN patients compared to healthy human volunteers
      and high mHsp70 expression levels on tumor cells were associated with high sHsp70
      levels in the serum of patients. Following surgery and radiotherapy sHsp70 levels
      in patients dropped in patients without tumor relapse in the follow-up period. In
      contrast to sHsp70 protein, anti-Hsp70 antibody levels remained nearly unaltered
      in the serum of SCCHN patients before and after therapy. Furthermore, sHsp70
      protein but not anti-Hsp70 antibody levels were found to be associated with the
      tumor volume in SCCHN patients before start of therapy. The expression densities
      of the activatory NK cell markers CD56, CD94, NKG2D, NKp30, Nkp44, and NKp46
      differed in patients following therapeutic intervention. A significant increase
      in the density of NKG2D was observed in SCCHN patients in the follow-up period
      after surgery and radiotherapy. CONCLUSION: We suggest sHsp70 as a potential
      biomarker for detecting tumors and for monitoring the clinical outcome of
      radiotherapy in SCCHN patients.

PMID- 24912483
TI  - Risk of death or hospital admission among community-dwelling older adults living
      with dementia in Australia.
AB  - BACKGROUND: Older people living with dementia prefer to stay at home to receive
      support. But they are at high risk of death and/or hospital admissions. This
      study primarily aimed to determine risk factors for time to death or hospital
      admission (combined) in a sample of community-dwelling older people living with
      dementia in Australia. As a secondary study purpose, risk factors for time to
      death were also examined. METHODS: This study used the data of a previous project
      which had been implemented during September 2007 and February 2009. The original
      project had recruited 354 eligible clients (aged 70 and over, and living with
      dementia) for Extended Aged Care At home Dementia program services during
      September 2007 and 2008. Client information and carer stress had been collected
      from their case managers through a baseline survey and three-monthly follow-up
      surveys (up to four in total). The principal data collection tools included
      Global Deterioration Scale, Modified Barthel Index, Instrumental-Dependency OARS,
      Adapted Cohen-Mansfield Agitation Inventory, as well as measures of clients'
      socio-demographic characteristics, service use and diseases diagnoses. The sample
      of our study included 284 clients with at least one follow-up survey. The outcome
      variable was death or hospital admission, and death during six, nine and 16-month
      study periods. Stepwise backwards multivariate Cox proportional hazards analysis
      was employed, and Kaplan-Meier survival analysis using censored data was
      displayed. RESULTS: Having previous hospital admissions was a consistent risk
      factor for time to death or hospital admission (six-month: HR = 3.12; nine-month:
      HR = 2.80; 16-month: HR = 2.93) and for time to death (six-month: HR = 2.27; 16
      month: HR = 2.12) over time. Previously worse cognitive status was a consistent
      risk factor over time (six- and nine-month: HR = 0.58; 16-month: HR = 0.65), but
      no previous use of community care was only a short-term risk factor (six-month:
      HR = 0.42) for time to death or hospital admission. CONCLUSIONS: Previous
      hospital admissions and previously worse cognitive status are target intervention
      areas for reducing dementia clients' risk of time to death or hospital admission,
      and/or death. Having previous use of community care as a short-term protective
      factor for dementia clients' time to death or hospital admission is noteworthy.

PMID- 24912484
TI  - Performance comparison of four exome capture systems for deep sequencing.
AB  - BACKGROUND: Recent developments in deep (next-generation) sequencing technologies
      are significantly impacting medical research. The global analysis of protein
      coding regions in genomes of interest by whole exome sequencing is a widely used
      application. Many technologies for exome capture are commercially available; here
      we compare the performance of four of them: NimbleGen's SeqCap EZ v3.0, Agilent's
      SureSelect v4.0, Illumina's TruSeq Exome, and Illumina's Nextera Exome, all
      applied to the same human tumor DNA sample. RESULTS: Each capture technology was
      evaluated for its coverage of different exome databases, target coverage
      efficiency, GC bias, sensitivity in single nucleotide variant detection,
      sensitivity in small indel detection, and technical reproducibility. In general,
      all technologies performed well; however, our data demonstrated small, but
      consistent differences between the four capture technologies. Illumina
      technologies cover more bases in coding and untranslated regions. Furthermore,
      whereas most of the technologies provide reduced coverage in regions with low or
      high GC content, the Nextera technology tends to bias towards target regions with
      high GC content. CONCLUSIONS: We show key differences in performance between the
      four technologies. Our data should help researchers who are planning exome
      sequencing to select appropriate exome capture technology for their particular
      application.

PMID- 24912485
TI  - A randomized study of standard versus double dose oseltamivir for treating
      influenza in the community.
AB  - BACKGROUND: The neuraminidase inhibitors are the treatment of choice for
      influenza virus infection. Oseltamivir-resistant (OsR) strains of influenza
      A(H1N1)pdm09 are described, but the effect of higher dose oseltamivir on
      efficacy, safety and emergence of resistance has not been addressed in the
      developed setting in outpatients. The objectives of the study were to compare
      standard dose (SD) versus double dose (DD) oseltamivir regimens for frequency of
      detecting OsR influenza virus, clinical disease resolution, virological clearance
      and adverse events. METHODS: This was an unblinded randomized controlled trial of
      community-based patients with confirmed influenza. Participants were randomized
      to a 5-day regimen of either SD or DD oseltamivir. RESULTS: Of 52 participants
      (aged 4.8-54.8 years), 25 received SD and 27 DD oseltamivir. Clinical resolution
      did not differ by dosing regimen (P=0.43); neither did virological clearance
      differ for either influenza A (P=0.20) or B (P=0.70). Adverse events,
      predominantly gastrointestinal, were greater with DD than SD (P=0.04). One OsR
      strain was detected prior to treatment and two individuals developed OsR strains
      during treatment, one each on SD and DD. Those with OsR strains did not appear to
      have a different clinical course. CONCLUSIONS: DD oseltamivir did not appear to
      provide a clinical or virological advantage, nor reduce the emergence of
      oseltamivir resistance, but our study was underpowered. Adverse events occurred
      more frequently on DD compared to SD oseltamivir.

PMID- 24912486
TI  - Comparative evaluation of high-flow nasal cannula and conventional oxygen therapy
      in paediatric cardiac surgical patients: a randomized controlled trial.
AB  - OBJECTIVES: The aim of this study was to compare high-flow nasal cannula (HFNC)
      and conventional O2 therapy (OT) in paediatric cardiac surgical patients; the
      primary objective of the study was to evaluate whether HFNC was able to improve
      PaCO2 elimination in the first 48 h after extubation postoperatively. METHODS: We
      conducted a randomized, controlled trial in pediatric cardiac surgical patients
      under 18 months of age. At the beginning of the weaning of ventilation, patients
      were randomly assigned to either of the following groups: OT or HFNC. Arterial
      blood samples were collected before and after extubation at the following time
      points: 1, 6, 12, 24 and 48 h. The primary outcome was comparison of arterial
      PaCO2 postextubation; secondary outcomes were PaO2 and PaO2/fractional inspired
      oxygen (FiO2) ratio, rate of treatment failure and need of respiratory support,
      rate of extubation failure, rate of atelectasis, simply to complications and the
      length of paediatric cardiac intensive care unit stay. RESULTS: Demographic and
      clinical variables were comparable in the two groups. Analysis of variance for
      repeated measures showed that PaCO2 was not significantly different between the
      HFNC and OT groups (P = 0.5), whereas PaO2 and PaO2/FiO2 were significantly
      improved in the HFNC group (P = 0.01 and P = 0.001). The rate of reintubation was
      not different in the two groups (P = 1.0), whereas the need for noninvasive
      respiratory support was 15% in the OT group and none in the HFNC group (P =
      0.008). CONCLUSIONS: HFNC had no impact on PaCO2 values. The use of HFNC appeared
      to be safe and improved PaO2 in paediatric cardiac surgical patients.

PMID- 24912487
TI  - Performance of piglets in response to the standardized ileal digestible
      phenylalanine and tyrosine supply in low-protein diets.
AB  - Reducing the CP level of the diet allows for a reduction in N excretion without
      limiting performance as long as the amino acid (AA) requirements are covered. The
      availability of crystalline AA has permitted for a considerable reduction in the
      CP level of diets, practically used in pig nutrition. The adoption of low CP
      diets and the extent to which the CP content can be reduced further depends on
      the knowledge of the minimum levels of indispensable AA that maximize growth. The
      standardized ileal digestible (SID) Phe : Lys and Tyr : Lys requirements and the
      possibility to substitute Tyr by Phe have never been studied in piglets. The
      objectives of this study were to estimate these requirements in 10 to 20 kg pig
      as well as to determine the extent to which Phe can be used to cover the Tyr
      requirement. In three dose-response studies, six pigs within each of 14 blocks
      were assigned to six low CP diets (14.5% CP) sub-limiting in Lys at 1.00% SID. In
      experiment 1, the SID Phe : Lys requirement estimate was assessed by
      supplementing a Phe-deficient diet with different levels of l-Phe to attain 33%,
      39%, 46%, 52%, 58%, and 65% SID Phe : Lys. Because Phe can be used for Tyr
      synthesis, the diets provided a sufficient Tyr supply. A similar approach was
      used in experiment 2 with six levels of l-Tyr supplementation to attain 21%, 27%,
      33%, 39%, 45% and 52% SID Tyr : Lys. Phenylalanine was supplied at a level
      sufficient to sustain maximum growth (estimated in experiment 1). The SID Phe :
      Lys and SID Tyr : Lys requirements for maximizing daily gain were 54% and 40%
      using a curvilinear-plateau model, respectively. A 10% deficiency in Phe and Tyr
      reduced daily gain by 3.0% and 0.7%, respectively. In experiment 3, the effect of
      the equimolar substitution of dietary SID Tyr by Phe to obtain 50%, 57%, and 64%
      SID Phe : (Phe+Tyr) was studied at two limiting levels of Phe+Tyr. From 57% to
      64% SID Phe : (Phe+Tyr), performance was slightly reduced. In conclusion, it is
      recommended not to use a Phe+Tyr requirement in the ideal AA profile but rather
      use a SID Phe : Lys of 54% and a SID Tyr : Lys of 40% to support maximal growth. 

PMID- 24912488
TI  - The maximum specific hydrogen-producing activity of anaerobic mixed cultures:
      definition and determination.
AB  - Fermentative hydrogen production from wastes has many advantages compared to
      various chemical methods. Methodology for characterizing the hydrogen-producing
      activity of anaerobic mixed cultures is essential for monitoring reactor
      operation in fermentative hydrogen production, however there is lack of such kind
      of standardized methodologies. In the present study, a new index, i.e., the
      maximum specific hydrogen-producing activity (SHAm) of anaerobic mixed cultures,
      was proposed, and consequently a reliable and simple method, named SHAm test, was
      developed to determine it. Furthermore, the influences of various parameters on
      the SHAm value determination of anaerobic mixed cultures were evaluated.
      Additionally, this SHAm assay was tested for different types of substrates and
      bacterial inocula. Our results demonstrate that this novel SHAm assay was a
      rapid, accurate and simple methodology for determining the hydrogen-producing
      activity of anaerobic mixed cultures. Thus, application of this approach is
      beneficial to establishing a stable anaerobic hydrogen-producing system. 

PMID- 24912489
TI  - Anastrozole and everolimus in advanced gynecologic and breast malignancies:
      activity and molecular alterations in the PI3K/AKT/mTOR pathway.
AB  - BACKGROUND: Since PI3K/AKT/mTOR pathway activation diminishes the effects of
      hormone therapy, combining aromatase inhibitors (anatrozole) with mTOR inhibitors
      (everolimus) was investigated. PATIENTS AND METHODS: We evaluated anastrozole and
      everolimus in 55 patients with metastatic estrogen (ER) and/or progesterone
      receptor (PR)-positive breast and gynecologic tumors. Endpoints were safety,
      antitumor activity and molecular correlates. RESULTS: Full doses of anastrozole
      (1 mg PO daily) and everolimus (10 mg PO daily) were well tolerated. Twelve of 50
      evaluable patients (24%) (median = 3 prior therapies) achieved stable disease
      (SD) >= 6 months/partial response (PR)/complete response (CR) (n = 5 (10%) with
      PR/CR): 9 of 32 (28%) with breast cancer (n=5 (16%) with PR/CR); 2 of 10 (20%),
      ovarian cancer; and 1 of 6 (17%), endometrial cancer. Six of 22 patients (27%)
      with molecular alterations in the PI3K/AKT/mTOR pathway achieved SD >= 6
      months/PR/CR. Six of 8 patients (75%) with SD >= 6 months/PR/CR with molecular
      testing demonstrated at least one alteration in the PI3K/AKT/mTOR pathway:
      mutations in PIK3CA (n=3) and AKT1 (n=1) or PTEN loss (n=3). All three responders
      (CR (n = 1); PR (n=2)) who had next generation sequencing demonstrated additional
      alterations: amplifications in CCNE1, IRS2, MCL1, CCND1, FGFR1 and MYC and a
      rearrangement in PRKDC. CONCLUSIONS: Combination anastrozole and everolimus is
      well tolerated at full approved doses, and is active in heavily-pretreated
      patients with ER and/or PR-positive breast, ovarian and endometrial cancers.
      Responses were observed in patients with multiple molecular aberrations. CLINICAL
      TRAILS INCLUDED: NCT01197170.

PMID- 24912490
TI  - Association between plasma levels of hyaluronic acid and functional outcome in
      acute stroke patients.
AB  - BACKGROUND: Activation of hyaluronic acid (HA) and associated enzyme synthesis
      has been demonstrated in experimental stroke animal models. Our study aimed to
      investigate the plasma levels of HA in acute stroke patients and the associations
      between HA levels and functional outcome. METHODS: This was a multicenter case
      control study. Acute stroke patients and age- and sex-matched non-stroke controls
      were recruited. Plasma levels of HA in acute stroke patients were determined at
      <48 hours and at 48 to 72 hours after stroke onset by standard ELISA. Favorable
      functional outcome was defined as modified Rankin scale <= 2 at 3 months after
      stroke. RESULTS: The study included 206 acute stroke patients, including 43 who
      had intracerebral hemorrhage and 163 who had ischemic stroke, and 159 controls.
      The plasma levels of HA in the acute stroke patients were significantly higher
      than those in the controls (219.7 +/- 203.4 ng/ml for <48 hours and 343.1 +/-
      710.3 ng/ml for 48 to 72 hours versus 170.4 +/- 127.9 ng/ml in the controls; both
      P  <  0.05). For intracerebral hemorrhage patients, HA <= 500 ng/ml (<48 hours)
      was an independent favorable outcome predictor (P = 0.016). For ischemic stroke
      patients, an inverted U-shaped association between plasma HA (48 to 72 hours) and
      outcome was noted, indicating that ischemic stroke patients with too high or too
      low plasma HA levels tended to have an unfavorable outcome. CONCLUSION: HA plasma
      level was elevated in patients with acute stroke, and can predict 3-month
      functional outcome, particularly for patients with intracerebral hemorrhage.

PMID- 24912491
TI  - Stimulant-induced dopamine increases are markedly blunted in active cocaine
      abusers.
AB  - Dopamine signaling in nucleus accumbens is essential for cocaine reward.
      Interestingly, imaging studies have reported blunted dopamine increases in
      striatum (assessed as reduced binding of [(11)C]raclopride to D2/D3 receptors) in
      detoxified cocaine abusers. Here, we evaluate whether the blunted dopamine
      response reflected the effects of detoxification and the lack of cocaine-cues
      during stimulant exposure. For this purpose we studied 62 participants (43 non
      detoxified cocaine abusers and 19 controls) using positron emission tomography
      and [(11)C]raclopride (radioligand sensitive to endogenous dopamine) to measure
      dopamine increases induced by intravenous methylphenidate and in 24 of the
      cocaine abusers, we also compared dopamine increases when methylphenidate was
      administered concomitantly with a cocaine cue-video versus a neutral-video. In
      controls, methylphenidate increased dopamine in dorsal (effect size 1.4; P<0.001)
      and ventral striatum (location of accumbens) (effect size 0.89; P<0.001), but in
      cocaine abusers methylphenidate's effects did not differ from placebo and were
      similar whether cocaine-cues were present or not. In cocaine abusers despite the
      markedly attenuated dopaminergic effects, the methylphenidate-induced changes in
      ventral striatum were associated with intense drug craving. Our findings are
      consistent with markedly reduced signaling through D2 receptors during
      intoxication in active cocaine abusers regardless of cues exposure, which might
      contribute to compulsive drug use. 

PMID- 24912492
TI  - Loss of neuronal GSK3beta reduces dendritic spine stability and attenuates
      excitatory synaptic transmission via beta-catenin.
AB  - Central nervous glycogen synthase kinase 3beta (GSK3beta) is implicated in a
      number of neuropsychiatric diseases, such as bipolar disorder, depression,
      schizophrenia, fragile X syndrome or anxiety disorder. Many drugs employed to
      treat these conditions inhibit GSK3beta either directly or indirectly. We studied
      how conditional knockout of GSK3beta affected structural synaptic plasticity.
      Deletion of the GSK3beta gene in a subset of cortical and hippocampal neurons in
      adult mice led to reduced spine density. In vivo imaging revealed that this was
      caused by a loss of persistent spines, whereas stabilization of newly formed
      spines was reduced. In electrophysiological recordings, these structural
      alterations correlated with a considerable drop in the frequency and amplitude of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      dependent miniature excitatory postsynaptic currents. Expression of
      constitutively active beta-catenin caused reduction in spine density and
      electrophysiological alterations similar to GSK3beta knockout, suggesting that
      the effects of GSK3beta knockout were mediated by the accumulation of beta
      catenin. In summary, changes of dendritic spines, both in quantity and in
      morphology, are correlates of experience-dependent synaptic plasticity; thus,
      these results may help explain the mechanism of action of psychotropic drugs
      inhibiting GSK3beta. 

PMID- 24912493
TI  - Magnetic resonance spectroscopy and tissue protein concentrations together
      suggest lower glutamate signaling in dentate gyrus in schizophrenia.
AB  - Hippocampal dysfunction in schizophrenia is widely acknowledged, yet the
      mechanism of such dysfunction remains debated. In this study we investigate the
      excitatory and inhibitory hippocampal neurotransmission using two complementary
      methodologies, proton magnetic resonance spectroscopy (MRS) and tissue
      biochemistry, sampling individuals with schizophrenia in vivo and postmortem
      hippocampal tissue in vitro. The results show significantly lower glutamate
      concentrations in hippocampus in schizophrenia, an in vivo finding mirrored by
      lower GluN1 protein levels selectively in the dentate gyrus (DG) in vitro. In a
      mouse model with a DG knockout of the GRIN1 gene, we further confirmed that a
      selective decrease in DG GluN1 is sufficient to decrease the glutamate
      concentrations in the whole hippocampus. Gamma-aminobutyric acid (GABA)
      concentrations and GAD67 protein were not significantly different in hippocampus
      in schizophrenia. Similarly, GABA concentrations in the hippocampi of mice with a
      DG knockout of the GRIN1 gene were not significantly different from wild type.
      These findings provide strong evidence implicating the excitatory system within
      hippocampus in the pathophysiology of schizophrenia, particularly indicating the
      DG as a site of pathology. 

PMID- 24912494
TI  - Meta-analysis: hoarding symptoms associated with poor treatment outcome in
      obsessive-compulsive disorder.
AB  - DSM-5 recognizes hoarding disorder as distinct from obsessive-compulsive disorder
      (OCD), codifying a new consensus. Hoarding disorder was previously classified as
      a symptom of OCD and patients received treatments designed for OCD. We conducted
      a meta-analysis to determine whether OCD patients with hoarding symptoms
      responded differently to traditional OCD treatments compared with OCD patients
      without hoarding symptoms. An electronic search was conducted for eligible
      studies in PubMed. A trial was eligible for inclusion if it (1) was a randomized
      controlled trial, cohort or case-control study; (2) compared treatment response
      between OCD patients with and those without hoarding symptoms, or examined
      response to treatment between OCD symptom dimensions (which typically include
      hoarding) and (3) examined treatment response to pharmacotherapy, behavioral
      therapy or their combination. Our primary outcome was differential treatment
      response between OCD patients with and those without hoarding symptoms, expressed
      as an odds ratio (OR). Twenty-one studies involving 3039 total participants
      including 304 with hoarding symptoms were included. Patients with OCD and
      hoarding symptoms were significantly less likely to respond to traditional OCD
      treatments than OCD patients without hoarding symptoms (OR=0.50 (95% confidence
      interval 0.42-0.60), z=-7.5, P<0.0001). This finding was consistent across
      treatment modalities. OCD patients with hoarding symptoms represent a population
      in need of further treatment research. OCD patients with hoarding symptoms may
      benefit more from interventions specifically targeting their hoarding symptoms.

PMID- 24912495
TI  - Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF-1alpha
      expression in vivo.
AB  - The aim of our study was to elucidate the effect of tacrolimus (FK506) and of C-X
      C chemokine receptor type 4 (CXCR4), which is a receptor specific to the stromal
      cell-derived factor-1alpha (SDF-1alpha), on growth and metastasis of
      hepatocellular carcinoma (HCC). Following treatment with different concentrations
      of FK506, AMD3100 or normal saline (NS), the proliferation of Morris rat hepatoma
      3924A (MH3924A) cells was measured by the MTT assay, the expression of CXCR4 was
      analyzed with immunohistochemistry, and the morphological changes and the
      invasiveness of cells were studied with a transwell assay and under a scanning
      electron microscope, respectively. In addition, August Copenhagen Irish rat
      models implanted with tumor were used to examine the pathological changes and
      invasiveness of tumor in vivo, the expression of CXCR4 in tumor tissues and the
      expression of SDF-1alpha in the adjacent tissues to the HCC ones, using
      immunohistochemistry. In vitro, FK506 (100-1,000 ug/l) significantly promoted the
      proliferation of MH3924A cells (P<0.01), and increased the expression of CXCR4 in
      MH3924A cells, albeit with no significance (P>0.05). By contrast, AMD3100 had no
      effect on the proliferation of MH3924A cells, but significantly reduced the
      expression of CXCR4 (P<0.05). The invasiveness of MH3924A cells was significantly
      (P<0.01) enhanced following treatment with FK506, SDF-1alpha, FK506 + AMD3100,
      FK506 + SDF-1alpha or FK506 + AMD3100 + SDF-1alpha. In vivo, tumor weight
      (P=0.041), lymph node metastasis (P=0.002), the number of pulmonary nodules
      (P=0.012), the expression of CXCR4 in tumor tissues (P=0.048) and that of SDF
      1alpha in adjacent tissues (P=0.026) were significantly different between the
      FK506-treated and the NS group. Our results suggest that FK506 promotes the
      proliferation of MH3924A cells and the expression of CXCR4 and SDF-1alpha in
      vivo. Therefore, inhibiting the formation of the CXCR4/SDF-1alpha complex may
      partly reduce the promoting effect of FK506 on HCC. 

PMID- 24912496
TI  - Conceptual model for dietary behaviour change at household level: a 'best-fit'
      qualitative study using primary data.
AB  - BACKGROUND: Interventions having a strong theoretical basis are more efficacious,
      providing a strong argument for incorporating theory into intervention planning.
      The objective of this study was to develop a conceptual model to facilitate the
      planning of dietary intervention strategies at the household level in rural
      Kerala. METHODS: Three focus group discussions and 17 individual interviews were
      conducted among men and women, aged between 23 and 75 years. An interview guide
      facilitated the process to understand: 1) feasibility and acceptability of a
      proposed dietary behaviour change intervention; 2) beliefs about foods,
      particularly fruits and vegetables; 3) decision-making in households with
      reference to food choices and access; and 4) to gain insights into the kind of
      intervention strategies that may be practical at community and household level.
      The data were analysed using a modified form of qualitative framework analysis,
      which combined both deductive and inductive reasoning. A priori themes were
      identified from relevant behaviour change theories using construct definitions,
      and used to index the meaning units identified from the primary qualitative data.
      In addition, new themes emerging from the data were included. The associations
      between the themes were mapped into four main factors and its components, which
      contributed to construction of the conceptual model. RESULTS: Thirteen of the a
      priori themes from three behaviour change theories (Trans-theoretical model,
      Health Belief model and Theory of Planned Behaviour) were confirmed or slightly
      modified, while four new themes emerged from the data. The conceptual model had
      four main factors and its components: impact factors (decisional balance, risk
      perception, attitude); change processes (action-oriented, cognitive); background
      factors (personal modifiers, societal norms); and overarching factors
      (accessibility, perceived needs and preferences), built around a three-stage
      change spiral (pre-contemplation, intention, action). Decisional balance was the
      strongest in terms of impacting the process of behaviour change, while household
      efficacy and perceived household cooperation were identified as 'markers' for
      stages-of-change at the household level. CONCLUSIONS: This type of framework
      analysis made it possible to develop a conceptual model that could facilitate the
      design of intervention strategies to aid a household-level dietary behaviour
      change process.

PMID- 24912497
TI  - Oleanolic acid induces protective autophagy in cancer cells through the JNK and
      mTOR pathways.
AB  - Autophagy is a biological process that eliminates damaged or excessive proteins
      and is utilized by various types of cells to maintain cellular homeostasis.
      Autophagy also occurs in cancer cells and exerts anti-survival or pro-survival
      effects depending on stimuli, nutrient and context. Oleanolic acid (OA), a widely
      spread natural compound, induces apoptosis in a range of cancer cells. However,
      some tumor cell lines are resistant to the pro-apoptotic effect of OA, and the
      mechanism remains unknown. In the present study, we found that OA induced
      autophagic event in cancer cells in a dose- and time-dependent manner, evidenced
      by an increased ratio between LC3-II and LC3-I and frequent granulation of LC3
      proteins in OA-stimulated tumor cell lines. Inhibition of autophagy potentiated
      the pro-apoptotic activity of OA on cancer cells. Furthermore, the JNK and mTOR
      signaling pathways were found to be affected by OA treatment. Interfering with
      JNK and mTOR abolished OA-induced autophagy and sensitized cancer cells to
      apoptosis. Collectively, we showed that OA was able to initiate protective
      autophagy, which compromised the antitumor activity of OA on cancer cells.
      Blocking autophagy may be a promising strategy to enhance the tumor suppressor
      activity of OA.

PMID- 24912498
TI  - Inflammatory and myeloid-associated gene expression before and one day after
      infant vaccination with MVA85A correlates with induction of a T cell response.
AB  - BACKGROUND: Tuberculosis (TB) remains a global health problem, with vaccination
      likely to be a necessary part of a successful control strategy. Results of the
      first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG
      vaccinated infants were published last year. Although no improvement in efficacy
      above BCG alone was seen, cryopreserved samples from this trial provide an
      opportunity to study the immune response to vaccination in this population.
      METHODS: We investigated blood samples taken before vaccination (baseline) and
      one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-gamma
      ELISpot assay was performed at baseline and on day 28 to quantify the adaptive
      response to Ag85A peptides. Gene expression analysis was performed at all three
      timepoints to identify early gene signatures predictive of the magnitude of the
      subsequent adaptive T cell response using the significance analysis of
      microarrays (SAM) statistical package and gene set enrichment analysis. RESULTS:
      One day post-MVA85A, there is an induction of inflammatory pathways compared to
      placebo samples. Modules associated with myeloid cells and inflammation pre- and
      one day post-MVA85A correlate with a higher IFN-gamma ELISpot response post
      vaccination. By contrast, previous work done in UK adults shows early
      inflammation in this population is not associated with a strong T cell response
      but that induction of regulatory pathways inversely correlates with the magnitude
      of the T cell response. This may be indicative of important mechanistic
      differences in how T cell responses develop in these two populations following
      vaccination with MVA85A. CONCLUSION: The results suggest the capacity of MVA85A
      to induce a strong innate response is key to the initiation of an adaptive immune
      response in South African infants but induction of regulatory pathways may be
      more important in UK adults. Understanding differences in immune response to
      vaccination between populations is likely to be an important aspect of developing
      successful vaccines and vaccination strategies. TRIAL REGISTRATION:
      ClinicalTrials.gov number NCT00953927.

PMID- 24912501
TI  - Electronic structure variation of the surface and bulk of a LiNi0.5Mn1.5O4
      cathode as a function of state of charge: X-ray absorption spectroscopic study.
AB  - The electronic structure at the Ni, Mn and O sites and their evolution upon the
      electrochemical lithiation of Li(1-x)Ni0.5Mn1.5O4 (LNMO) in a lithium ion battery
      has been explored using comprehensive X-ray absorption near edge structure
      spectroscopy (XANES) at the Ni and Mn L3,2- and O K-edges, with both surface
      sensitive and bulk-sensitive detection. It has confirmed that Ni reduction from
      Ni(4+) to Ni(2+) plays the leading role in charge compensation when the
      lithiation voltage is above 4.5 V. Our study also unveils the participation of
      oxygen in the charge compensation. Furthermore, the enhanced difference in the
      electronic structures of the surface and bulk in electrochemically cycled
      samples, and the different surface electronic structures of the fully discharged
      LNMO and the pristine one, highlight the importance of electrochemical
      activation. These findings are critical for a better understanding of the
      electrochemical reaction of LNMO and the influence of structural modifications to
      the surface region upon its performance, and will assist further efforts to
      improve this high-voltage cathode material for its application in lithium ion
      batteries.

PMID- 24912499
TI  - REGNET: mining context-specific human transcription networks using composite
      genomic information.
AB  - BACKGROUND: Genome-wide expression profiles reflect the transcriptional networks
      specific to the given cell context. However, most statistical models try to
      estimate the average connectivity of the networks from a collection of gene
      expression data, and are unable to characterize the context-specific
      transcriptional regulations. We propose an approach for mining context-specific
      transcription networks from a large collection of gene expression fold-change
      profiles and composite gene-set information. RESULTS: Using a composite gene-set
      analysis method, we combine the information of transcription factor binding
      sites, Gene Ontology or pathway gene sets and gene expression fold-change
      profiles for a variety of cell conditions. We then collected all the significant
      patterns and constructed a database of context-specific transcription networks
      for human (REGNET). As a result, context-specific roles of transcription factors
      as well as their functional targets are readily explored. To validate the
      approach, nine predicted targets of E2F1 in HeLa cells were tested using
      chromatin immunoprecipitation assay. Among them, five (Gadd45b, Dusp6, Mll5, Bmp2
      and E2f3) were successfully bound by E2F1. c-JUN and the EMT transcription
      networks were also validated from literature. CONCLUSIONS: REGNET is a useful
      tool for exploring the ternary relationships among the transcription factors,
      their functional targets and the corresponding cell conditions. It is able to
      provide useful clues for novel cell-specific transcriptional regulations. The
      REGNET database is available at http://mgrc.kribb.re.kr/regnet.

PMID- 24912500
TI  - Medical students as peer tutors: a systematic review.
AB  - BACKGROUND: While Peer Assisted Learning (PAL) has long occurred informally in
      medical education, in the past ten years, there has been increasing international
      interest in formally organised PAL, with many benefits for both the students and
      institutions. We conducted a systematic review of the literature to establish why
      and how PAL has been implemented, focussing on the recruitment and training
      process for peer tutors, the benefits for peer tutors, and the competency of peer
      tutors. METHOD: A literature search was conducted in three electronic databases.
      Selection of titles and abstracts were made based on pre-determined eligibility
      criteria. We utilized the 'AMEE Peer assisted learning: a planning and
      implementation framework: AMEE Guide no. 30' to assist us in establishing the
      review aims in a systematic review of the literature between 2002 and 2012. Six
      key questions were developed and used in our analysis of particular aspects of
      PAL programs within medical degree programs. RESULTS: We found nineteen articles
      that satisfied our inclusion criteria. The PAL activities fell into three broad
      categories of teacher training, peer teaching and peer assessment. Variability
      was found in the reporting of tutor recruitment and training processes, tutor
      outcomes, and tutor competencies. CONCLUSION: Results from this review suggest
      that there are many perceived learning benefits for student tutors. However,
      there were mixed results regarding the accuracy of peer assessment and feedback,
      and no substantial evidence to conclude that participation as a peer tutor
      improves one's own examination performance. Further research into PAL in medicine
      is required if we are to better understand the relative impact and benefits for
      student tutors.

PMID- 24912502
TI  - Effects of balancing crystalline amino acids in diets containing heat-damaged
      soybean meal or distillers dried grains with solubles fed to weanling pigs.
AB  - Two experiments were conducted to investigate if adjustments in diet formulations
      either based on total analysed amino acids or standardized ileal digestible (SID)
      amino acids may be used to eliminate negative effects of including heat-damaged
      soybean meal (SBM) or heat-damaged corn distillers dried grains with solubles
      (DDGS) in diets fed to weanling pigs. In Experiment 1, four corn-SBM diets were
      formulated. Diet 1 contained non-autoclaved SBM (315 g/kg), and this diet was
      formulated on the basis of analysed amino acid concentrations and using SID
      values from the AminoDat(r) 4.0 database. Diet 2 was similar to Diet 1 in terms
      of ingredient composition, except that the non-autoclaved SBM was replaced by
      autoclaved SBM at 1 : 1 (weight basis). Diet 3 was formulated using autoclaved
      SBM and amino acid inclusions in the diet were adjusted on the basis of analysed
      total amino acid concentrations in the autoclaved SBM and published SID values
      for non-autoclaved SBM (AminoDat(r) 4.0). Diet 4 also contained autoclaved SBM,
      but the formulation of this diet was adjusted on the basis of analysed amino
      acids in the autoclaved SBM and SID values that were adjusted according to the
      degree of heat damage in this source of SBM. Pigs (160; initial BW: 10.4 kg) were
      allotted to the four treatments with eight replicate pens per treatment in a
      randomized complete block design. Diets were fed to pigs for 21 days. The gain to
      feed ratio (G : F) was greater (P<0.05) for pigs fed Diet 1 compared with pigs
      fed the other diets and pigs fed Diet 4 had greater (P<0.05) G : F than pigs fed
      Diet 2. In Experiment 2, 144 pigs (initial BW: 9.9 kg) were allotted to four
      diets with eight replicate pens per diet. The four diets contained corn, SBM (85
      g/kg) and DDGS (220 g/kg), and were formulated using the concepts described for
      Experiment 1, except that heat-damaged DDGS, but not heat-damaged SBM, was used
      in the diets. Pigs fed Diet 1 had greater (P<0.05) G : F than pigs fed Diet 2,
      but no differences were observed for G : F among pigs fed diets containing
      autoclaved DDGS. Results demonstrate that the negative effects of heat damage of
      SBM or DDGS may be ameliorated if the reduced concentration and digestibility of
      amino acids in heat-damaged SBM or DDGS is taken into account in diet
      formulation. Further research is needed to improve the prediction of the ileal
      digestibility of amino acids in heat-processed ingredients used in practical diet
      formulations.

PMID- 24912503
TI  - Complex influence of dermatan sulphate on breast cancer cells.
AB  - Tumor transformation and progression both lead to extracellular matrix
      remodeling, which is also reflected in an alteration in the proportion of
      dermatan sulphate (DS) and chondroitin sulphate (CS) and an accumulation of the
      latter. In addition, a significant increase in the 6-O-sulphated disaccharide
      contribution to the structure of both glycosaminoglycans has been observed. It is
      commonly accepted that CS is more permissive for tumor growth than DS. However,
      the detailed role of DS in tumor progression is poorly known. We tested the
      effects of structurally different DSs on the behavior of cultured breast cancer
      cells. At a high dose (10 ug/mL), all of the DSs significantly reduced cancer
      cell growth, although some differences in the efficiency of action were apparent.
      In contrast, when used at a concentration of 1 ug/mL, the examined DSs evoked
      different responses ranging from the stimulation to the inhibition of cancer cell
      proliferation. The highest stimulatory activity was associated with fibrosis
      affected fascia decorin DS, which is characterized by a particularly high content
      of 6-O-sulphated disaccharides. Further reduction in DS concentration to 0.5
      ug/mL preserved majority of biological effects which were apparent at a dose of 1
      ug/mL. The enzymatic fragmentation of the DSs, particularly by chondroitinase AC
      I, abolished the impact exerted by 1 ug/mL of the intact DS chains and sometimes
      resulted in the opposite effect. In contrast to DSs, highly sulphated C-6-S
      exhibited no effect on the cancer cells. Our data revealed the complexity of the
      effects of DSs on breast cancer cells, which include both co-receptor activity
      and the prevention of vascular endothelial growth factor action. In addition, the
      biological effect of DSs is strongly dependent not only on the glycosaminoglycan
      structure but also on its content in the cancer environment. 

PMID- 24912504
TI  - Protective effect of quercetin on lipopolysaccharide-induced acute lung injury in
      mice by inhibiting inflammatory cell influx.
AB  - Sepsis may result in lung injury through a complex cascade of events including
      interstitium infiltration of inflammatory cells. Quercetin, the most abundant
      dietary flavonoid found in various plants and food products, possesses potent
      anti-inflammatory and antioxidative properties. The purpose of this study was to
      investigate whether preventive administration of quercetin could exert beneficial
      effects on experimental septic acute lung injury induced by lipopolysaccharide
      (LPS). C57/BL6 mice were challenged with LPS and survival time was monitored from
      0-96 h after LPS treatment. Quercetin markedly rescued lethality, improved
      survival time, and inhibited serum necrosis factor alpha, interleukin 1beta, and
      interleukin 6, and nitric oxide (NO), and increased IL-10 secretion. Moreover,
      quercetin decreased lung pathological changes, myeloperoxidase activity, and
      malondialdehyde levels. Quercetin also reduced the lung permeability changes and
      neutrophil and macrophage recruitment to the bronchoalveolar lavage fluid
      compared to the vehicle. Additionally, quercetin significantly reduced COX-2,
      HMGB1, iNOS expression, and NF-kappaB p65 phosphorylation. These results suggest
      that treatment with quercetin in septic mice improved survival time and lung
      injury. Quercetin may be a promising potential therapeutic reagent for LPS
      induced acute lung injury. 

PMID- 24912507
TI  - Zeb1 promotes androgen independence of prostate cancer via induction of stem cell
      like properties.
AB  - Current androgen deprivation therapy often leads to androgen independence.
      However, mechanism of the therapeutic failure is still not well understood. Here,
      we demonstrate elevated expression of Zeb1 in androgen-independent prostate
      cancer cells and prostate tumors of castrated PTEN conditional knockout mice.
      While Zeb1 shRNA resulted in a sensitization of androgen-independent prostate
      cancer cells, forced Zeb1 expression caused androgen-dependent prostate cancer
      cells to be more resistant to androgen deprivation. Moreover, such effects
      appeared to be mediated by induction of pluripotent genes or stem cell-like
      properties. Collectively, these findings suggest that inhibition of Zeb1 might be
      a potential therapeutic strategy for treatment of androgen-independent prostate
      cancer.

PMID- 24912508
TI  - Bilateral hearing loss as a manifestation of neuromyelitis optica.

PMID- 24912505
TI  - Biological and medical applications of a brain-on-a-chip.
AB  - The desire to develop and evaluate drugs as potential countermeasures for
      biological and chemical threats requires test systems that can also substitute
      for the clinical trials normally crucial for drug development. Current animal
      models have limited predictivity for drug efficacy in humans as the large
      majority of drugs fails in clinical trials. We have limited understanding of the
      function of the central nervous system and the complexity of the brain,
      especially during development and neuronal plasticity. Simple in vitro systems do
      not represent physiology and function of the brain. Moreover, the difficulty of
      studying interactions between human genetics and environmental factors leads to
      lack of knowledge about the events that induce neurological diseases.
      Microphysiological systems (MPS) promise to generate more complex in vitro human
      models that better simulate the organ's biology and function. MPS combine
      different cell types in a specific three-dimensional (3D) configuration to
      simulate organs with a concrete function. The final aim of these MPS is to
      combine different "organoids" to generate a human-on-a-chip, an approach that
      would allow studies of complex physiological organ interactions. The recent
      discovery of induced pluripotent stem cells (iPSCs) gives a range of
      possibilities allowing cellular studies of individuals with different genetic
      backgrounds (e.g., human disease models). Application of iPSCs from different
      donors in MPS gives the opportunity to better understand mechanisms of the
      disease and can be a novel tool in drug development, toxicology, and medicine. In
      order to generate a brain-on-a-chip, we have established a 3D model from human
      iPSCs based on our experience with a 3D rat primary aggregating brain model.
      After four weeks of differentiation, human 3D aggregates stain positive for
      different neuronal markers and show higher gene expression of various neuronal
      differentiation markers compared to 2D cultures. Here we present the applications
      and challenges of this emerging technology.

PMID- 24912509
TI  - Spice, pot, and stroke.

PMID- 24912506
TI  - Physiology and metabolism of tissue-engineered skeletal muscle.
AB  - Skeletal muscle is a major target for tissue engineering, given its relative size
      in the body, fraction of cardiac output that passes through muscle beds, as well
      as its key role in energy metabolism and diabetes, and the need for therapies for
      muscle diseases such as muscular dystrophy and sarcopenia. To date, most studies
      with tissue-engineered skeletal muscle have utilized murine and rat cell sources.
      On the other hand, successful engineering of functional human muscle would enable
      different applications including improved methods for preclinical testing of
      drugs and therapies. Some of the requirements for engineering functional skeletal
      muscle include expression of adult forms of muscle proteins, comparable
      contractile forces to those produced by native muscle, and physiological force
      length and force-frequency relations. This review discusses the various
      strategies and challenges associated with these requirements, specific
      applications with cultured human myoblasts, and future directions. 

PMID- 24912510
TI  - Prognostic or predictive value of MGMT promoter methylation in gliomas depends on
      IDH1 mutation.

PMID- 24912514
TI  - [Prevalence and factors associated with puncture injuries among medical
      students].

PMID- 24912512
TI  - MGMT testing--the challenges for biomarker-based glioma treatment.
AB  - Many patients with malignant gliomas do not respond to alkylating agent
      chemotherapy. Alkylator resistance of glioma cells is mainly mediated by the DNA
      repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). Epigenetic
      silencing of the MGMT gene by promoter methylation in glioma cells compromises
      this DNA repair mechanism and increases chemosensitivity. MGMT promoter
      methylation is, therefore, a strong prognostic biomarker in paediatric and adult
      patients with glioblastoma treated with temozolomide. Notably, elderly patients
      (>65-70 years) with glioblastoma whose tumours lack MGMT promoter methylation
      derive minimal benefit from such chemotherapy. Thus, MGMT promoter methylation
      status has become a frequently requested laboratory test in neuro-oncology. This
      Review presents current data on the prognostic and predictive relevance of MGMT
      testing, discusses clinical trials that have used MGMT status to select
      participants, evaluates known issues concerning the molecular testing procedure,
      and addresses the necessity for molecular-context-dependent interpretation of
      MGMT test results. Whether MGMT promoter methylation testing should be offered to
      all individuals with glioblastoma, or only to elderly patients and those in
      clinical trials, is also discussed. Justifications for withholding alkylating
      agent chemotherapy in patients with MGMT-unmethylated glioblastomas outside
      clinical trials, and the potential role for MGMT testing in other gliomas, are
      also discussed. 

PMID- 24912515
TI  - Short-term effect of physical activity and obesity on disability in a sample of
      rural elderly in Mexico.
AB  - OBJECTIVE: To estimate the effects of physical activity (PA) and obesity on the
      cumulative incidence of disability on the basic activities of daily living in the
      elderly. MATERIALS AND METHODS: Longitudinal study. We selected 2477 participants
      aged 65-74 years from the impact evaluation study of a non-contributory pension
      program in Mexico. Participants were without disability at baseline. Katz index
      was used to assess disability both at baseline and follow-up. PA, body mass
      index, and covariates were measured at baseline. RESULTS: After 14-months of
      follow-up, the cumulative incidence of disability reached 10.1%. High PA was
      found to reduce disability risk (OR=0.64; 95%CI [0.43-0.95]), and the association
      between obesity and disability was marginally significant (OR=1.36; 95%CI [0.96
      1.95]). CONCLUSIONS: There is a need to perform a functional assessment of older
      adults in primary care to identify patients with functional dependence , and to
      promote physical activity to maintain muscle mass and thus reduce the incidence
      of disability.

PMID- 24912513
TI  - Neuropathic pruritus.
AB  - Pruritus, also known as itch, is a very common, unpleasant sensation that elicits
      an urge to scratch. Its origin is not always in the skin, and neuropathic itch
      that is caused by neuronal or glial damage is common, but poorly understood by
      both dermatologists and neurologists. Although pruritus has not been considered
      as serious a symptom as pain, it is difficult to treat and--if chronic--can
      severely impair quality of life. Neuropathic itch is often associated with other
      clinical symptoms, most commonly neuropathic pain, and hypersensitization to
      stimuli is present in both pruritus and pain of neuropathic origin. The shared
      aetiology can aid in finding suitable treatment for itch in some cases, but more
      detailed knowledge of the mechanisms of itch, along with standardized, well
      controlled trials, is needed. Pruritus research is an emerging but currently very
      active field, and our understanding of this sensation is rapidly increasing.
      Here, we review new discoveries regarding the role of the nervous system and the
      contribution of different pathways in pruritus, discuss the different aetiologies
      of neuropathic itch, and outline currently available and potential strategies for
      managing neuropathic pruritus.

PMID- 24912516
TI  - Incidence of type 2 diabetes in Mexico: results of the Mexico City Diabetes Study
      after 18 years of follow-up.
AB  - OBJECTIVE: To estimate the incidence of type 2 diabetes (T2D) in Mexican
      population. MATERIALS AND METHODS: Population based prospective study. At
      baseline (1990), the population at risk (1939 non-diabetic adults 35-64 years)
      was evaluated with oral glucose tolerance test. Subsequent similar evaluations
      were done (1994, 1998, 2008). American Diabetes Association diagnostic criteria
      were applied. RESULTS: The period of observation was 27842 person-years, the
      cumulative incidence of T2D was 14.4 and 13.7 per 1000 person-years for men and
      women, respectively. Incidence was 15.8, 15.7 and 12.7 per 1 000 person-years for
      the second (1994), third (1998) and fourth (2008) follow-up phases, respectively.
      The mean age at diagnosis was 44 years for prevalent cases and 56 years for
      incident cases. CONCLUSIONS: This is the first estimate of long-term incidence of
      T2D in Mexican population. The incidence is among the highest reported worldwide.
      It remained with few changes throughout the study period.

PMID- 24912517
TI  - [Analysis of outpatient healthcare utilization in the context of the universal
      healthcare coverage reform in Mexico].
AB  - OBJECTIVE: Understand and quantify the relationship between socio-economic and
      health insurance profiles and the use of outpatient medical services in the
      context of universal health care in Mexico. MATERIALS AND METHODS: Using ENSANUT
      2012 multinomial regression models were estimated to analyze the use of
      outpatient services and associated factors. RESULTS: Population with greater
      poverty levels, lower educational level and living in highly marginalized areas
      have lower odds to use outpatient health services. In contrast, health insurance
      and higher income increase the odds to use health services and influence the
      choice of provider. CONCLUSIONS: Barriers to access to health care related to
      poverty and social protection persist. However, there is space to lower the
      effect of these barriers by addressing constraints linked to the supply and the
      perceived quality of healthcare services.

PMID- 24912519
TI  - [Psychometric properties of the Dating Abuse Questionnaire in a sample of Mexican
      female students of middle and higher level].
AB  - OBJECTIVE: The aim of the study was to modify and adapt the questionnaire Dating
      Abuse Italy-Mexico binational version (CMN) to a sample of female students of
      middle and higher level, from the Federal District and the State of Mexico.
      MATERIALS AND METHODS: Cross-sectional study. 2157 students participated, aged
      between 14 and 33 years old. The reagents were analyzed using item-scale method,
      and was applied a confirmatory factor analysis. RESULTS: The CMN showed an
      internal consistency of alpha= 0.95, the Confirmatory factor analysis confirmed
      the five theoretical areas planned with satisfactory fit indices. CONCLUSIONS:
      The psychometric characteristics of this version of CMN are adequate to reliably
      assess abuse in dating.

PMID- 24912518
TI  - [Prenatal care and hospital maternal mortality in Tijuana, Baja California,
      Mexico].
AB  - OBJECTIVE: To describe the prenatal care (PC) received in women with maternal
      hospital deaths from 2005 to 2011 in Tijuana, Baja California, Mexico. MATERIALS
      AND METHODS: Were reviewed the medical chars and registrations of the maternal
      deaths by the local Committees of Maternal Mortality. RESULTS: There were 44
      maternal hospital deaths. Thirty (68%) women assisted to PC appointments during
      pregnancy, the average number of PC visits was 3.8 and 18 (41%) had an adequate
      PC (>= 5 visits). Six (14%) women didn't know they were pregnant; 19 (43%), 21
      (48%) y 4 (9%) maternal deaths were due to direct, indirect obstetric cause or
      non-obstetric causes. Eighteen (18%), 2 (4 %) and 34 (77%) of the maternal deaths
      occurred during pregnancy, delivery or puerperium. CONCLUSIONS: It is necessary
      pregnancy women have an early, periodic and systematic PC to identify opportunely
      risk factors associated with pregnancy complications.

PMID- 24912520
TI  - [Parents willingness to pay for a human papillomavirus vaccine to protect their
      adolescent daughters: Maule Region, Chile].
AB  - OBJECTIVE: To determine the willingness to pay of parents of teenage daughters
      for a vaccine against human papillomavirus in the Maule Region, Chile. MATERIALS
      AND METHODS: A sample of 386 parents with daughters between 12 and 18 years old,
      representing the five largest cities of the Region of Maule, socioeconomically
      stratified. WTP was obtained using the contingent valuation method in double
      bounded format. RESULTS: Parents are willing to pay an average of US$ 252.71 to
      vaccinate their daughters against virus, where the price and number of daughters
      negatively affects the probability of willingness to pay, and family income
      positively affects the probability. CONCLUSION: There is a possibility of using
      shared funding between the government and the parents of potential daughter to be
      affected by the human papillomavirus to reduce cervical cancer events.

PMID- 24912521
TI  - [Between the stigma and the law: legal abortion in Mexico City].
AB  - The present contribution is part of a research developed with qualitative social
      research methods. It offers part of the results attained in a study performed at
      a clinic belonging to Mexico City's Government, and explores the effects on staff
      of the implementation of Legal Pregnancy Termination (ILE, for its initials in
      Spanish). The results highlights that, besides diminishing health risks in the
      women who abort, the use of misoprostol prompted assertive attitudes in many
      women, that reduced the negative effects produced by the stigma of abortion. It
      also acknowledges the persistence of stigma in the opinions of the health
      personnel. The empowering of the self-image of women who become subject to this
      procedure is due to the full exercise of their legal right.

PMID- 24912522
TI  - Drug resistance and molecular epidemiology of Mycobacterium tuberculosis in
      Mexico: a systematic review.
AB  - OBJECTIVE: To compare drug resistance (DR) rates and genetic diversity of
      Mycobacterium tuberculosis strains from different states of Mexico. MATERIALS AND
      METHODS: A systematic review of English and Spanish-language articles using
      MEDLINE and Google Scholar. Search terms included Mycobacterium tuberculosis,
      Mexico, resistance, mutation and epidemiology. RESULTS: Fifteen studies for
      phenotypic DR rates (n=2 694), twelve studies for genotypic DR (n=748) and eleven
      studies for genetic diversity (n=2 044) met our inclusion criteria. Mean DR and
      multidrug resistance (MDR) rates were 37.5% and 20.6%, respectively. The most
      frequent mutations were rpoB531 (53.1%), katG315 (50.6%), embB306 (32.1%), rpsL43
      (14.6%) and pncA359 (16.7%) in DR strains. Novel mutations were found.
      Predominant shared types were SIT53 (T1, n=188, 3.9%), SIT119 (X1, n=125, 6.9%),
      SIT19 (EAI2-Manila, n=80, 6.3%) and SIT42 (LAM9, n=77, 3.0%). SIT1 Beijing
      genotype has been reported in six states from Mexico. CONCLUSIONS: DR and MDR
      rates continue to increase. Genetic diversity of M. tuberculosis strains in
      Mexico is high. Reports of Beijing strains are increasing.

PMID- 24912524
TI  - A novel proteasome inhibitor suppresses tumor growth via targeting both 19S
      proteasome deubiquitinases and 20S proteolytic peptidases.
AB  - The successful development of bortezomib-based therapy for treatment of multiple
      myeloma has established proteasome inhibition as an effective therapeutic
      strategy, and both 20S proteasome peptidases and 19S deubiquitinases (DUBs) are
      becoming attractive targets of cancer therapy. It has been reported that metal
      complexes, such as copper complexes, inhibit tumor proteasome. However, the
      involved mechanism of action has not been fully characterized. Here we report
      that (i) copper pyrithione (CuPT), an alternative to tributyltin for antifouling
      paint biocides, inhibits the ubiquitin-proteasome system (UPS) via targeting both
      19S proteasome-specific DUBs and 20S proteolytic peptidases with a mechanism
      distinct from that of the FDA-approved proteasome inhibitor bortezomib; (ii) CuPT
      potently inhibits proteasome-specific UCHL5 and USP14 activities; (iii) CuPT
      inhibits tumor growth in vivo and induces cytotoxicity in vitro and ex vivo. This
      study uncovers a novel class of dual inhibitors of DUBs and proteasome and
      suggests a potential clinical strategy for cancer therapy. 

PMID- 24912526
TI  - Neutrophil/lymphocyte ratio is related to the severity of idiopathic dilated
      cardiomyopathy.
AB  - OBJECTIVES: The aim of this study was to assess whether NLR levels are associated
      with echocardiographic parameters, New York Heart Association (NYHA) functional
      class, or B- type natriuretic peptide (BNP) levels in patients with idiopathic
      dilated cardiomyopathy (DCM). DESIGN: Eighty-seven patients with idiopathic DCM
      were included prospectively from 2009 to 2014. Patients with acute decompensated
      heart failure and conditions that alter the total or differential white blood
      cell counts were excluded. Blood samples were collected before echocardiographic
      investigation on admission. RESULTS: There was a statistically significant
      correlation between neutrophil/lymphocyte ratio (NLR) and NYHA functional class
      (r = 0.68, p < 0.001), BNP levels (r = 0.61, p < 0.001) and various
      echocardiographic parameters. NLR was significantly higher in patients in NYHA
      functional class III or IV (n = 39) than among those categorized as NYHA class I
      or II (n = 48), (3.3 +/- 1.0 vs 2.1 +/- 0.6; p < 0.001). The NLR cutoff value
      predicting severe chronic HF was 2.25 with 82% sensitivity and 65% specificity (p
      < 0.001). On multivariate linear regression analysis NLR (p = 0.025), left
      ventricular end-diastolic volume (p = 0.041) and left atrial volume index (LAVI)
      (p = 0.001) were found to be independent positive predictors of BNP levels.
      CONCLUSION: Neutrophil/Lymphocyte ratio is associated with the severity of
      chronic heart failure in patients with idiopathic DCM.

PMID- 24912525
TI  - HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1.
AB  - BACKGROUND: The Vpr protein of human immunodeficiency virus type 1 (HIV-1) plays
      an important role in viral replication. It has been reported that Vpr stimulates
      the nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) signaling
      pathways, and thereby regulates viral and host cell gene expression. However, the
      molecular mechanism behind this function of Vpr is not fully understood. RESULTS:
      Here, we have identified transforming growth factor-beta-activated kinase 1
      (TAK1) as the important upstream signaling molecule that Vpr associates with in
      order to activate NF-kappaB and AP-1 signaling. HIV-1 virion-associated Vpr is
      able to stimulate phosphorylation of TAK1. This activity of Vpr depends on its
      association with TAK1, since the S79A Vpr mutant lost interaction with TAK1 and
      was unable to activate TAK1. This association allows Vpr to promote the
      interaction of TAB3 with TAK1 and increase the polyubiquitination of TAK1, which
      renders TAK1 phosphorylation. In further support of the key role of TAK1 in this
      function of Vpr, knockdown of endogenous TAK1 significantly attenuated the
      ability of Vpr to activate NF-kappaB and AP-1 as well as the ability to stimulate
      HIV-1 LTR promoter. CONCLUSIONS: HIV-1 Vpr enhances the phosphorylation and
      polyubiquitination of TAK1, and as a result, activates NF-kappaB and AP-1
      signaling pathways and stimulates HIV-1 LTR promoter.

PMID- 24912527
TI  - Heat shock protein 90 as a potential drug target against surra.
AB  - Trypanosomiasis is caused by Trypanosoma species which affect both human and
      animal populations and pose a major threat to developing countries. The incidence
      of animal trypanosomiasis is on the rise. Surra is a type of animal
      trypanosomiasis, caused by Trypanosoma evansi, and has been included in priority
      list B of significant diseases by the World Organization of Animal Health (OIE).
      Control of surra has been a challenge due to the lack of effective drugs and
      vaccines and emergence of resistance towards existing drugs. Our laboratory has
      previously implicated Heat shock protein 90 (Hsp90) from protozoan parasites as a
      potential drug target and successfully demonstrated efficacy of an Hsp90
      inhibitor in cell culture as well as a pre-clinical mouse model of
      trypanosomiasis. This article explores the role of Hsp90 in the Trypanosoma life
      cycle and its potential as a drug target. It appears plausible that the
      repertoire of Hsp90 inhibitors available in academia and industry may have value
      for treatment of surra and other animal trypanosomiasis.

PMID- 24912528
TI  - A brief overview on IRM function across evolution.
AB  - The description of the Rst protein by Karl-Friedrich Fischbach and colleagues was
      a milestone in the discovery of the irre cell recognition module (IRM). IRM
      proteins represent a family of immunoglobulin superfamily cell adhesion proteins
      that orchestrate intercellular adhesion and signaling events necessary for the
      development of various tissues. This review briefly summarizes the fundamental
      role of IRM proteins for neuronal wiring and filtration in organisms spanning the
      evolutionary distance from Drosophila (nephrocyte diaphragm) to humans (slit
      diaphragm).

PMID- 24912529
TI  - Biphasic modulation of alpha-ENaC expression by lipopolysaccharide in vitro and
      in vivo.
AB  - Acute lung injury (ALI) is characterized by pulmonary edema, in which the
      epithelial sodium channel (ENaC) has a critical role in the clearance of edema
      fluid from the alveolar space. Lipopolysaccharide (LPS), frequently employed to
      induce ALI in experimental animal models, has been reported to regulate ENaC
      expression and alveolar fluid clearance. The role of LPS in regulating ENaC
      expression is currently controversial, with increases and decreases reported in
      ENaC expression in response to LPS treatment, as well as reports that ENaC
      expression is not affected by LPS induction. The present study aimed to
      systematically analyze the regulation of alpha-ENaC expression in LPS models of
      ALI at different pathological stages in vitro and in vivo. ENaC expression was
      observed to increase <=8 h after LPS treatment, and to decrease thereafter. This
      finding may explain the contradictory data regarding alpha-ENaC expression in
      response to LPS in the lung. The results of the present study, in combination
      with those of previous studies, indicate that the modulation of alpha-ENaC
      expression may not be a direct genetic response to LPS exposure, but a general
      response of the lung to the pathological changes associated with inflammation,
      hypoxia and endothelial and epithelial damage involved in the development of ALI.
      The findings of this study may have potential clinical significance for
      understanding the pathogenesis of ALI and improving patient outcome. 

PMID- 24912530
TI  - Gene expression profiling of HL-60 cells following knockdown of nucleostemin
      using DNA microarrays.
AB  - Nucleostemin (NS) plays an important role in tumorigenesis and progression. Most
      studies consider that NS plays its role through combining with p53 and inhibiting
      it, however our previous studies revealed that NS could also function without the
      existence of p53. To date, few studies have focused on the p53-independent
      pathway of NS, and its molecular mechanism remains unknown. The aim of the
      present study was to investigate the p53-independent pathway of NS in the human
      acute myeloid leukemia cell line HL-60 which was p53-null by using the DNA
      microarray technique. Lentivirus-mediated RNA interference technique was used to
      knock down NS expression in HL-60 cells, and then DNA microarray and
      bioinformatics were used to analyze the gene expression profiling changes. The
      microarray data showed that after knocking down NS in HL-60 cells, 2,628
      differentially expressed genes were identified through >= 2 or <= 0.5-fold
      change, in which 818 genes were upregulated and 1,810 genes were downregulated.
      Real-time quantitative polymerase chain reaction (qPCR) validated the reliability
      of DNA microarray data. Pathway analysis showed extensive signal pathways in HL
      60 cells were influenced by inhibiting NS expression. In particular, the
      inhibition of PI3K-AKT pathway, JAK-STAT pathway, RAS-RAF-MEK-ERK1/2 pathway and
      activation of JNK pathway, p38 MAPK pathway may associate with the apoptosis of
      HL-60 cells after knocking down NS. The findings of this study provide insight to
      further explore the specific molecular mechanism of NS function in p53-null
      leukemia and they also lay the foundations for exploring new therapeutic targets
      for p53-null leukemia and even p53-null tumors.

PMID- 24912531
TI  - Chronic diseases and multi-morbidity--a conceptual modification to the WHO ICCC
      model for countries in health transition.
AB  - BACKGROUND: The burden of non-communicable diseases is rising, particularly in
      low and middle-income countries undergoing rapid epidemiological transition. In
      sub-Saharan Africa, this is occurring against a background of infectious chronic
      disease epidemics, particularly HIV and tuberculosis. Consequently, multi
      morbidity, the co-existence of more than one chronic condition in one person, is
      increasing; in particular multimorbidity due to comorbid non-communicable and
      infectious chronic diseases (CNCICD). Such complex multimorbidity is a major
      challenge to existing models of healthcare delivery and there is a need to ensure
      integrated care across disease pathways and across primary and secondary care.
      DISCUSSION: The Innovative Care for Chronic Conditions (ICCC) Framework developed
      by the World Health Organization provides a health systems roadmap to meet the
      increasing needs of chronic disease care. This framework incorporates community,
      patient, healthcare and policy environment perspectives, and forms the
      cornerstone of South Africa's primary health care re-engineering and strategic
      plan for chronic disease management integration. However, it does not
      significantly incorporate complexity associated with multimorbidity and
      CNCICD.Using South Africa as a case study for a country in transition, we
      identify gaps in the ICCC framework at the micro-, meso-, and macro-levels. We
      apply the lens of CNCICD and propose modification of the ICCC and the South
      African Integrated Chronic Disease Management plan. Our framework incorporates
      the increased complexity of treating CNCICD patients, and highlights the
      importance of biomedicine (biological interaction). We highlight the patient
      perspective using a patient experience model that proposes that treatment
      adherence, healthcare utilization, and health outcomes are influenced by the
      relationship between the workload that is delegated to patients by healthcare
      providers, and patients' capacity to meet the demands of this workload. We link
      these issues to provider perspectives that interact with healthcare delivery and
      utilization. SUMMARY: Our proposed modification to the ICCC Framework makes clear
      that healthcare systems must work to make sense of the complex collision between
      biological phenomena, clinical interpretation, beliefs and behaviours that follow
      from these. We emphasize the integration of these issues with the socio-economic
      environment to address issues of complexity, access and equity in the integrated
      management of chronic diseases previously considered in isolation.

PMID- 24912532
TI  - Pharyngoesophageal reconstruction after resection of hypopharyngeal carcinoma: a
      new algorithm after analysis of 142 cases.
AB  - BACKGROUND: The aim of this study is to define an algorithm for the choice of
      reconstructive method for defects after laryngo-pharyngo-esophagectomy for
      hypopharyngeal carcinoma. METHODS: One hundred and forty two cases of
      hypopharyngeal carcinoma were included and operated on by either partial
      pharyngectomy, total pharyngectomy or esophagectomy. The reconstructive method
      was tailored according to the resected segment. RESULTS: Pectoralis flap was used
      in 48 cases, free jejunal flap in 28 cases, augmented colon bypass in 4 cases,
      gastric pull up in 32 cases and gastric tube in 30 cases. Mean hospital stay was
      12 days. Mortality rate was 10.6% and morbidity rate was 31.7%. Total flap
      failure occurred in 3 cases of free flap and one case of pectoralis flap. There
      were 23 cases of early fistula. Late stricture occurred in 19 cases, being
      highest with myocutaneous flap (early fistula 12/50 and late stricture 13/50).
      CONCLUSION: Free jejunal flap was the flap of choice for reconstruction when the
      safety margin is still above the clavicle. In cases with added esophagectomy, we
      recommend gastric tube as a method of choice for reconstruction.

PMID- 24912533
TI  - The pH of wound fluid in diabetic foot ulcers -- the way forward in detecting
      clinical infection?
AB  - Infections within diabetic foot ulcers are often hard to detect and extremely
      difficult to treat. The normal signs and symptoms of infection including
      purulence, erythema, pain, tenderness, warmth and induration are frequently
      absent in such wounds necessitating exploration of other ways of rapidly and
      accurately detecting infection. This study considers diabetic wound fluid pH as a
      possible alternative means of monitoring infection status. CINAHL, Ovid SP and
      MEDLINE were searched for papers in English published between January 2004 to May
      2014. Key search terms included wound fluid, exudate, wound, ulcer, diabetes, pH,
      healing, infection, bacteria. This paper considers the potential benefits of
      augmenting and supporting current clinical practice in the early determination of
      wound healing trajectory and infection status, by monitoring wound fluid pH. The
      evidence collected highlights the need for further research and suggests the
      potential of wound fluid analysis as a possible surrogate marker for detecting
      infection in diabetic foot ulcers. 

PMID- 24912534
TI  - Proteomics-based discovery of biomarkers for paediatric acute lymphoblastic
      leukaemia: challenges and opportunities.
AB  - There are important breakthroughs in the treatment of paediatric acute
      lymphoblastic leukaemia (ALL) since 1950, by which the prognosis of the child
      majority suffered from ALL has been improved. However, there are urgent needs to
      have disease-specific biomarkers to monitor the therapeutic efficacy and predict
      the patient prognosis. The present study overviewed proteomics-based research on
      paediatric ALL to discuss important advances to combat cancer cells and search
      novel and real protein biomarkers of resistance or sensitivity to drugs which
      target the signalling networks. We highlighted the importance and significance of
      a proper phospho-quantitative design and strategy for paediatric ALL between
      relapse and remission, when human body fluids from cerebrospinal, peripheral
      blood, or bone-marrow were applied. The present article also assessed the
      schedule for the analysis of body fluids from patients at different states,
      importance of proteomics-based tools to discover ALL-specific and sensitive
      biomarkers, to stimulate paediatric ALL research via proteomics to 'build' the
      reference map of the signalling networks from leukemic cells at relapse, and to
      monitor significant clinical therapies for ALL-relapse. 

PMID- 24912535
TI  - Outreach sexual infection screening and postal tests in men who have sex with
      men: are they comparable to clinic screening?
AB  - Men who have sex with men (MSM) have higher rates of poor sexual health. The
      National Institute for Health and Care Excellence has produced guidance on
      increasing the uptake of HIV testing to reduce undiagnosed infection in MSM. We
      report the results of a pilot outreach sexually transmitted infection service
      using nurse-delivered screening and self-sampled postal testing at a sex on
      premises venue with comparison made against a sexual health clinic service.
      Thirty men were included in each group. Users of the nurse-delivered and postal
      services were older (nurse service median age 57.5 years vs. postal kit service
      47 years vs. clinic 35.5 years, p <= 0.001). Outreach groups were less likely to
      have undertaken sexually transmitted infection testing previously than the clinic
      group (53.3% and 60% vs. 93.3%, p <= 0.001). Chlamydia trachomatis and Neisseria
      gonorrhoeae testing uptake was comparable across groups (nurse outreach 86.6%,
      'do it yourself' postal kit 100% vs. clinic 100%, p = 0.032), but uptake for
      blood tests was lower in the postal kit group (nurse outreach 83.3%, postal kit
      53.3% vs. clinic 100%, p <= 0.001). No significant difference in active sexually
      transmitted infection positivity across the groups was observed. This combination
      outreach screening approach is effective in targeting MSM who use sex on premises
      venues. 

PMID- 24912536
TI  - Atypical presentations of genital herpes simplex virus in HIV-1 and HIV-2
      effectively treated by imiquimod.
AB  - Atypical presentations of genital herpes simplex virus have been described in
      HIV. We report two cases with hypertrophic presentations which were effectively
      treated with imiquimod, one of which is the first reported case occurring in a
      patient with HIV-2. 

PMID- 24912537
TI  - Audit of the management of the syphilis outbreak in Herefordshire 2011-2013.
AB  - The objective of this audit was to evaluate a localised rural outbreak of
      syphilis against British Association of Sexual Health and HIV guidelines. Forty
      nine cases were identified; 98% were men, and 88% were men who have sex with men
      (MSM). There was a low incidence of HIV co-infection (18%). All standards
      regarding monitoring and treatment were met, whereas the standard concerning
      contact tracing was narrowly missed, highlighting a number of issues and areas
      for improvement. This audit has highlighted that a proactive approach is
      necessary to identify cases of syphilis in rural communities. This is due to
      difficulties in outreach testing and contact tracing in the absence of designated
      meeting places for MSM. 

PMID- 24912538
TI  - Social and psychosocial factors associated with high-risk sexual behaviour among
      university students in the United Kingdom: a web-survey.
AB  - In the UK there are limited data about university students' risky sexual
      behaviour. A cross-sectional web-survey was conducted to investigate factors
      associated with high-risk sex among students at two UK universities. High-risk
      sex was reported by 25% of 1108. High personal sexually transmitted infection
      (STI) risk perception and permissive attitudes towards casual sex were associated
      with high-risk sex for both men (odds ratio [OR]: 12.12; 95% confidence interval
      [CI]: 4.10-35.81; OR: 2.49; 95%CI: 1.11-5.56, respectively) and women (OR: 22.31;
      95% CI: 9.34-53.26; OR: 3.02; 95% CI: 1.82-5.01, respectively). For men, drinking
      alcohol (OR: 17.67; 95% CI: 1.90-164.23) and for women age and frequent drinking
      (OR: 2.02; 95% CI: 1.05-3.89; OR: 1.89; 95% CI: 1.08-3.31, respectively) were
      associated with high-risk sex. However, perceiving an average student as more
      likely to contract STIs (men, OR: 0.34; 95% CI: 0.16-0.75) or HIV (men, OR: 0.44;
      95% CI: 0.20-0.96; women, OR: 0.42; 95% CI: 0.28-0.63) and finding it difficult
      to discuss sexual matters (women, OR: 0.60; 95% CI: 0.39-0.91) were negatively
      associated with high-risk sex. Most of the factors found were similar to other
      populations, but some psychosocial factors showed complex patterns of association
      that require further investigation. 

PMID- 24912539
TI  - Behcet's disease diagnosed after acute HIV infection: viral replication
      activating underlying autoimmunity?
AB  - Behcet's disease is an autoimmune systemic vasculitis that can occur after
      exposure to infectious agents. Behcet's disease also has been associated with HIV
      infection, including de novo development of this condition during chronic HIV
      infection and resolution of Behcet's disease symptoms following initiation of
      antiretroviral therapy. We describe a patient who presented with systemic
      vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV
      infection, who was eventually diagnosed with Behcet's disease, demonstrating a
      possible link between acute HIV infection, immune activation and development of
      autoimmunity. 

PMID- 24912540
TI  - Serum ferritin in HIV-positive patients is related to immune deficiency and
      inflammatory activity.
AB  - To analyse the prevalence of high ferritin levels in asymptomatic HIV patients
      and its related factors we conducted a cross-sectional study of a cohort of HIV
      outpatients in regular follow-up. Epidemiological, clinical, analytical and
      therapeutic data were collected. Patients completed a questionnaire about
      cardiovascular risk factors and underwent a physical examination and a 12-h
      fasting blood analysis. High ferritin levels were defined as a plasma ferritin
      level >200 ug/L in women and >300 ug/L in men. A total of 571 patients (78.1%
      men) were included. Median age was 43.2 years, HIV sexual transmission 68.5%,
      median CD4 count 474 cells/uL, 36.3% AIDS cases, 86.2% on antiretroviral therapy
      and 74.8% of them with undetectable viral load; 14.6% metabolic syndrome
      criteria, and mean cardiovascular risk at 10 years 6.67%. High ferritin levels
      prevalence was 11%, and related factors were a CD4 count <350 cells/uL (odds
      ratio, OR 2.37 [1.3-4.1], p = 0.003), ultrasensitive C-reactive protein >3 mg/L
      (OR 2.67 [1.5-4.7], p = 0.001) and chronic hepatitis C virus infection (OR 2.77
      [1.5-4.9], p = 0.001). High ferritin levels are not uncommon in HIV patients, and
      they correlate with immunosuppression defined as CD4 count <350 cells/uL, higher
      ultrasensitive C-reactive protein and hepatitis C virus infection, and in
      contrast to the general population, they are not related to increased
      cardiovascular risk or metabolic syndrome. 

PMID- 24912541
TI  - Practice of skin protection and skin care among German surgeons and influence on
      the efficacy of surgical hand disinfection and surgical glove perforation.
AB  - BACKGROUND: Surgical hand rub and healthy skin are basic requirements to prevent
      surgical site infections. Nevertheless, there is little knowledge about the
      current practice of skin protection and/or skin care products (SP/SC) using among
      surgeons as well as a lack of data pertaining to the influence of SP/SC on the
      antimicrobial efficacy of surgical hand rub. METHODS: A 10 weeks-survey among
      German surgeons as well as an experimental crossover study involving 26
      participants were conducted. The immediate and sustainable efficacy (IE/SE) of
      surgical hand rub and participants' hand moisture were measured after an 8-day
      usage of SP/SC, as well as the influence on micro-perforations on surgical
      gloves. RESULTS: The questionnaire was available to 16,000 German surgeons.
      Thereof, 1,771 surgeons accessed the questionnaire, representing a total
      participation rate of 11%. As 19% (n = 338) of questionnaires were incomplete, a
      total of 1,433 completed questionnaires were available for further analysis. More
      than 75% of the participants stated not to use any SP/SC, yet, almost 50%
      suffered from skin irritation or discomfort. Only 5% used SP/SC at the beginning
      of their shift. 10% refused to use SP/SC because of concerns that SP/SC may
      reduce the antimicrobial efficacy of surgical hand rub.After usage of SP/SC over
      8-days, skin moisture was significantly higher (P < 0.001), whereas no
      significant influence on the antimicrobial efficacy of surgical hand rub was
      observed (IE: P = 0.135; SP: P = 0.681). Micro-perforations were detected in 8/52
      surgical gloves (15%), with no statistical significant difference between SP/SC
      users (n = 2/26; 8%) and non-users (n = 6/26; 23%; P = 0.249). CONCLUSIONS:
      Following the results of this largest questionnaire base survey among German
      surgeons on skin care, there is a need to educate and inform surgeons on the
      correct application and the concept of SP/SC strategies. In the present study,
      the combination of selected SP/SC products and one alcohol-based hand rub
      formulation did not show a negative interaction with surgical hand rub or
      surgical glove perforation. However, it is advisable to ascertain the
      compatibility of SP/SC products with the used hand disinfectant prior to
      purchase.

PMID- 24912542
TI  - An integrated platform for bovine DNA methylome analysis suitable for small
      samples.
AB  - BACKGROUND: Oocytes and early embryos contain minute amounts of DNA, RNA and
      proteins, making the study of early mammalian development highly challenging. The
      study of the embryo epigenome, in particular the DNA methylome, has been made
      accessible thanks to the possibility of amplifying specific sequences according
      to their initial methylation status. This paper describes a novel platform
      dedicated to the genome-wide study of bovine DNA methylation, including a
      complete pipeline for data analysis and visualization. The platform allows
      processing and integrating of DNA methylome and transcriptome data from the same
      sample. Procedures were optimized for genome-wide analysis of 10 ng of DNA (10
      bovine blastocysts). Bovine sperm and blastocysts were compared as a test of
      platform capability. RESULTS: The hypermethylation of bovine sperm DNA compared
      to the embryo genome was confirmed. Differentially methylated regions were
      distributed across various classes of bovine sperm genomic feature including
      primarily promoter, intronic and exonic regions, non-CpG-island regions (shore,
      shelf and open-sea) and CpG islands with low-to-intermediate CpG density. The
      blastocyst genome bore more methylation marks than sperm DNA only in CpG islands
      with high CpG density. Long-terminal-repeat retrotransposons (LTR), LINE and SINE
      were more methylated in sperm DNA, as were low-complexity repetitive elements in
      blastocysts. CONCLUSIONS: This is the first early embryo compatible genome-wide
      epigenetics platform for bovine. Such platforms should improve the study of the
      potential epigenetic risks of assisted reproductive technologies (ART), the
      establishment sequence of embryonic cell lines and potential deviations in both
      gene expression and DNA methylation capable of having long-term impact.

PMID- 24912543
TI  - OsHK3 is a crucial regulator of abscisic acid signaling involved in antioxidant
      defense in rice.
AB  - In this study, the role of the rice (Oryza sativa L.) histidine kinase OsHK3 in
      abscisic acid (ABA)-induced antioxidant defense was investigated. Treatments with
      ABA, H2 O2 , and polyethylene glycol (PEG) induced the expression of OsHK3 in
      rice leaves, and H2 O2 is required for ABA-induced increase in the expression of
      OsHK3 under water stress. Subcellular localization analysis showed that OsHK3 is
      located in the cytoplasm and the plasma membrane. The transient expression
      analysis and the transient RNA interference test in rice protoplasts showed that
      OsHK3 is required for ABA-induced upregulation in the expression of antioxidant
      enzymes genes and the activities of antioxidant enzymes. Further analysis showed
      that OsHK3 functions upstream of the calcium/calmodulin-dependent protein kinase
      OsDMI3 and the mitogen-activated protein kinase OsMPK1 to regulate the activities
      of antioxidant enzymes in ABA signaling. Moreover, OsHK3 was also shown to
      regulate the expression of nicotinamide adenine dinucleotide phosphate oxidase
      genes, OsrbohB and OsrbohE, and the production of H2 O2 in ABA signaling. Our
      data indicate that OsHK3 play an important role in the regulation of ABA-induced
      antioxidant defense and in the feedback regulation of H2 O2 production in ABA
      signaling. 

PMID- 24912544
TI  - The value of area-based analyses of donation patterns for recruitment strategies.
AB  - BACKGROUND: Lack of ready access to a donation site may be a potential barrier to
      or influence the frequency of blood donations. In this study, we applied
      geographic analysis to blood donor behavior and use of different donation sites.
      STUDY DESIGN AND METHODS: The study population consisted of blood donors who gave
      whole blood in Georgia between 2004 and 2008. Zip code, city, and county of
      donor's residence were matched with the addresses of their donation sites. Donors
      were dichotomized as either nonmetro Atlanta or metro Atlanta residents. Six
      donation site categories were defined: donation within the same or a different
      zip code, within the same or a different city, and within the same or a different
      county. Logistic regression was used to compare donations by zip code, city, and
      county. RESULTS: The study population consisted of 402,692 blood donors who
      donated 1,147,442 whole blood units between 2004 and 2008, more than half of whom
      (56.4%) resided in the metro Atlanta area. The majority of donors were white
      (75.0%) and female (55.7%). In nonmetro Atlanta, repeat donors were more likely
      to have donated at fixed sites (p < 0.001). In metro Atlanta, repeat donors were
      more likely to have donated at a mobile site than at a fixed site (p < 0.001).
      CONCLUSION: Geographic and demographic differences in blood donation patterns
      exist. The locations of donor residences and blood donation sites influence donor
      behaviors. Understanding the geographic influence on donation patterns provides
      an important tool for optimizing donor recruitment strategies.

PMID- 24912545
TI  - Free voiding patterns in preterm and full-term newborn infants are different
      between males and females.
AB  - AIM: The neonatal period is critical in bladder development, encompassing the
      transition from foetal bladder contractions to voluntary infant urination. The
      aim of this study was to investigate different voiding parameters between male
      and female newborn infants. METHODS: We studied 102 healthy, single birth newborn
      infants - 54 preterm and 48 full-term - without lower urinary tract diseases,
      hospitalised in the neonatal intensive care unit from March 2011 to March 2012.
      Free voiding was observed from 9 a.m. to 9 p.m., and the free voiding parameters
      and fluid intake were recorded and compared between male and female newborn
      infants using the Student's t-test and chi-square test. RESULTS: Male preterm
      newborns demonstrated larger mean postvoid residual volumes and lower bladder
      emptying rates than female preterm newborns (p < 0.05), and male full-term
      newborns had lower bladder emptying rates than female full-term newborns (p <
      0.05). The bladder emptying rates of newborns defecating simultaneously with
      voiding were not statistically different between males and females of the same
      gestational age (p > 0.05). CONCLUSION: Male newborns were more likely to have
      larger postvoid residual volumes than females, and defecating simultaneously with
      voiding may promote bladder emptying in male newborns.

PMID- 24912546
TI  - Spinal cord injury models: a review.
AB  - BACKGROUND: Animal spinal cord injury (SCI) models have proved invaluable in
      better understanding the mechanisms involved in traumatic SCI and evaluating the
      effectiveness of experimental therapeutic interventions. Over the past 25 years,
      substantial gains have been made in developing consistent, reproducible and
      reliable animal SCI models. STUDY DESIGN: Review. OBJECTIVE: The objective of
      this review was to consolidate current knowledge on SCI models and introduce
      newer paradigms that are currently being developed. RESULTS: SCI models are
      categorized based on the mechanism of injury into contusion, compression,
      distraction, dislocation, transection or chemical models. Contusion devices
      inflict a transient, acute injury to the spinal cord using a weight-drop
      technique, electromagnetic impactor or air pressure. Compression devices compress
      the cord at specific force and duration to cause SCI. Distraction SCI devices
      inflict graded injury by controlled stretching of the cord. Mechanical
      displacement of the vertebrae is utilized to produce dislocation-type SCI.
      Surgical transection of the cord, partial or complete, is particularly useful in
      regenerative medicine. Finally, chemically induced SCI replicates select
      components of the secondary injury cascade. Although rodents remain the most
      commonly used species and are best suited for preliminary SCI studies, large
      animal and nonhuman primate experiments better approximate human SCI. CONCLUSION:
      All SCI models aim to replicate SCI in humans as closely as possible. Given the
      recent improvements in commonly used models and development of newer paradigms,
      much progress is anticipated in the coming years.

PMID- 24912547
TI  - Efficacy comparison between minimally invasive and conventional surgery for
      lumbar disc herniation in Chinese Han population: a meta-analysis.
AB  - STUDY DESIGN: The pooled data were analyzed using RevMan 5.2 software.
      OBJECTIVES: The aim was to compare the efficacy of minimally invasive and
      conventional surgery for lumbar disc herniation (LDH) in Chinese Han population.
      SETTING: China. METHODS: An electronic search up to November 2013 was performed
      to retrieve all relevant articles. The overall standardized mean difference (SMD)
      for continuous outcomes and odds ratio (OR) for dichotomous variables as well as
      their 95% confidence intervals (CIs) were calculated to compare the efficacy of
      minimally invasive and conventional surgery. RESULTS: A total of 23 studies
      involving 1913 patients treated by minimally invasive surgery and 2295 patients
      treated by conversational surgery were included in this meta-analysis. The
      overall estimate indicated that minimally invasive surgery could significantly
      decrease the hospitalization time (SMD = -2.03, 95% CI, -2.49 to 1.56, P <
      0.0001), blood loss (SMD = -2.65, 95% CI -3.33 to 1.97, P < 0.0001), incision
      length (SMD = -3.57, 95% CI, -4.39 to 2.75, P < 0.0001), recurrence rate (odds
      ratio (OR) = 0.22, 95 CI: 0.08-0.60, P = 0.003) and complications (OR = 0.47, 95%
      CI: 0.25-0.92, P = 0.03) and increase the postoperative excellent rate (OR =
      1.82, 95% CI, 1.44-2.31, P < 0.0001) compared with conventional surgery. In
      addition, the pooled data showed that there was no statistically significant
      difference in the operative time (SMD = -0.58, 95% CI, -1.32 to 0.15, P = 0.12)
      between LDH patients treated by minimally invasive and conventional surgery.
      CONCLUSION: In conclusion, minimally invasive surgery was a more safe and
      effective treatment for treating LDH in Chinese Han population when compared with
      conventional surgery.

PMID- 24912548
TI  - Long-term urological management in spinal injury units in the U.K. and Eire: a
      follow-up study.
AB  - AIMS: The majority of patients with spinal cord injury (SCI) will develop
      neurogenic lower urinary tract dysfunction (NLUTD). These patients require a long
      term urological follow-up. The follow-up protocol has varied across SCI units in
      the United Kingdom and Eire. We reviewed the long-term management in the SCI
      units to identify changes in practice over a decade and compared them to current
      guidelines. METHODS: We present results of a review of all SCI centres in the
      United Kingdom and Eire on their long-term urological management before and after
      the current guidelines and compared the results with European Association of
      Urology (EAU) Guidelines on NLUTD and the proposed British guidelines for the
      urological management of patients with SCI. Data were collected through
      questionnaires posted to SCI units. RESULTS: SCI patients are followed up in
      outpatients annually in the SCI centres and the frequency of follow-up remains
      largely unchanged. More SCI units perform renal tract imaging annually as a part
      of SCI follow-up. Most units follow the proposed British guideline indications
      for urodynamics and do not perform 'routine urodynamics'. CONCLUSIONS: We
      conclude that the long-term management of SCI patients in SCI units in the United
      Kingdom and Eire has changed overtime to follow the proposed British guidelines.
      EAU guidelines offer a more extensive follow-up regime. Last, there is a
      continued lack of high-quality evidence to support an optimal long-term follow-up
      protocol. Importantly, there is a lack of evidence on clinical outcomes when
      these guidelines have been followed.

PMID- 24912549
TI  - Clinical analysis following lumbar interspinous devices implant: where we are and
      where we go.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVES: We present our experience with
      patients treated with interspinous devices who are affected by neurogenic
      intermittent claudication (NIC) or lumbar disc herniation (LDH) where the
      interspinous system has been inserted following microdiscectomy. METHODS: This
      study included patients (n = 100) with NIC secondary to lumbar spinal stenosis
      (group 1), and patients (n = 100) with LDH (group 2) in whom the interspinous
      device has been implanted following radicular decompression in a period spanning
      6 years. The latter have been compared with a homogenous group of patients (n =
      100) where no interspinous system has been implanted following microdiscectomy
      (group 3). Clinical findings have been observed preoperatively and 3, 6, 12
      months and every year post-operatively using dedicated questionnaires (Zurich
      Claudication Questionnaire, Visual Analog Scale and Oswestry Disability Index).
      RESULTS: Six years following surgical treatment, 85% of the patients of group 1
      presented good improvement of symptoms and 90% of the patients referred
      satisfaction for surgery. Only few cases needed reoperation. In one case, the
      device was removed and in two cases, we changed the surgical strategy. Overall,
      patients of group 2 presented significantly less lumbar disc recurrences compared
      with group 3 (P < 0.05) and better clinical outcome when compared with the same
      group (P < 0.01). CONCLUSION: According to our features, interspinous systems
      showed significant and clinically meaningful improvements in pain and disability
      for up to 6 years. Furthermore, interspinous devices have shown better clinical
      outcome and less lumbar disc recurrences when associated with standard
      microdiscectomy. These data, however, need further studies and a longer period of
      follow-up.

PMID- 24912550
TI  - Diffuse scattering in Ih ice.
AB  - Single crystals of ice Ih, extracted from the subglacial Lake Vostok accretion
      ice layer (3621 m depth) were investigated by means of diffuse x-ray scattering
      and inelastic x-ray scattering. The diffuse scattering was identified as mainly
      inelastic and rationalized in the frame of ab initio calculations for the ordered
      ice XI approximant. Together with Monte-Carlo modelling, our data allowed
      reconsidering previously available neutron diffuse scattering data of heavy ice
      as the sum of thermal diffuse scattering and static disorder contribution.

PMID- 24912551
TI  - Chronic migraine and medication overuse headache.

PMID- 24912552
TI  - Understanding the impact of special health care needs on early school
      functioning: a conceptual model.
AB  - Children with special health care needs (SHCN) have or are at increased risk for
      a chronic condition that necessitates more health and related supports than their
      peers. While it is generally accepted that these children are at risk for school
      failure, the mechanisms through which SHCN impact on children's experiences (and
      therefore opportunities to intervene) at school are still relatively poorly
      understood. Based on the current literature, this paper provides a conceptual
      framework to guide further discussion of this issue in research, policy and
      practice. Evidence from the literature was reviewed and existing frameworks
      examined. We propose that SHCN impact on four interrelated domains of children's
      functioning: (1) body functions and structures; (2) activities of daily living;
      (3) social participation; and (4) educational participation. Children's
      functioning is further influenced by risk and protective factors that can be
      identified at the level of the child, family and service systems. Together, these
      processes contribute to shaping either positive or negative trajectories of
      school functioning. The mechanisms influencing school experiences for children
      with special health care needs are complex, with opportunities for positive
      interventions at a range of levels. The proposed conceptual model provides an
      accessible tool for guiding discussion of the support needs of this vulnerable
      population. 

PMID- 24912553
TI  - Methylation of the filaggrin gene promoter does not affect gene expression and
      allergy.

PMID- 24912554
TI  - Toxic pyrene metabolism in Mycobacterium gilvum PYR-GCK results in the expression
      of mammalian cell entry genes as revealed by transcriptomics study.
AB  - Mycobacterium gilvum PYR-GCK is a bacterial strain under study for its
      bioremediation use on heavy hydrocarbon pollutants in the environment. During the
      course of our study, mammalian cell entry (mce) genes, known to facilitate
      pathogenicity in M. tuberculosis, were highly expressed during a comparative and
      substrate-related cultural global transcriptomic study. RNA sequencing of the
      global transcriptome of the test strain in two different substrates, pyrene and
      glucose, showed high expression of the mce genes based on the differential
      results. After validating the expression of these genes with quantitative real
      time PCR, we arrived at the conclusion that the genes were expressed based on the
      pyrene substrate (a phytosterol compound), and sterol metabolism is said to
      activate the expression of the mce genes in some actinomycetes bacteria, M.
      gilvum PYR-GCK in this case. This study is believed to be important based on the
      fact that some mycobacterial strains are undergoing a continuous research as a
      result of their use in practical bioremediation of anthropogenic exposure of
      toxic organic wastes in the environment. 

PMID- 24912555
TI  - Bacillus licheniformis isolated from Korean traditional food sources enhances the
      resistance of Caenorhabditis elegans to infection by Staphylococcus aureus.
AB  - We investigated whether Bacillus spp., newly isolated from Korean traditional
      food resources, influence the resistance of hosts to foodborne pathogens, by
      using Caenorhabditis elegans as a surrogate host model. Initially, we selected 20
      Bacillus spp. that possess antimicrobial activity against various foodborne
      pathogens, including Staphylococcus aureus. Among the selected strains, six
      strains of Bacillus spp. used in preconditioning significantly prolonged the
      survival of nematodes exposed to S. aureus. Based on 16S rRNA gene sequencing,
      all six strains were identified as B. licheniformis. Our findings suggest that
      preconditioning with B. licheniformis may modulate the host defense response
      against S. aureus. 

PMID- 24912556
TI  - Sequence validation for the identification of the white-rot fungi Bjerkandera in
      public sequence databases.
AB  - White-rot fungi of the genus Bjerkandera are cosmopolitan and have shown
      potential for industrial application and bioremediation. When distinguishing
      morphological characters are no longer present (e.g., cultures or dried specimen
      fragments), characterizing true sequences of Bjerkandera is crucial for accurate
      identification and application of the species. To build a framework for molecular
      identification of Bjerkandera, we carefully identified specimens of B. adusta and
      B. fumosa from Korea based on morphological characters, followed by sequencing
      the internal transcribed spacer region and 28S nuclear ribosomal large subunit.
      The phylogenetic analysis of Korean Bjerkandera specimens showed clear genetic
      differentiation between the two species. Using this phylogeny as a framework, we
      examined the identification accuracy of sequences available in GenBank. Analyses
      revealed that many Bjerkandera sequences in the database are either misidentified
      or unidentified. This study provides robust reference sequences for sequence
      based identification of Bjerkandera, and further demonstrates the presence and
      dangers of incorrect sequences in GenBank. 

PMID- 24912557
TI  - A mixed formulation of lactic acid bacteria inhibits trinitrobenzene-sulfonic
      acid-induced inflammatory changes of the colon tissue in mice.
AB  - Lactic acid bacteria (LAB) are probiotics that provide numerous beneficial
      effects on the host body, especially on the intestine. Combining several strains
      of LAB, we prepared a formulation containing four different LAB and studied its
      anti-inflammatory activity both in vitro and in vivo. The formulation
      significantly reduced NO production from RAW 264.7 cells treated with bacterial
      lipopolysaccharide, indicating that the formulation might include
      antiinflammatory activity. The formulation also suppressed inflammatory change
      induced by trinitrobenzene sulfonic acid (TNBS) in mice, where oral or rectal
      administration of the formulation protected the colon tissue from the damage by
      TNBS. Expressions of the IL-6 and FasL genes appeared to be down-regulated by the
      formulation in TNBS-treated colon tissues, suggesting that the suppression of
      those genes may be involved in the anti-inflammatory activity of the formulation.

PMID- 24912558
TI  - The hTAS2R38 genotype is associated with sugar and candy consumption in preschool
      boys.
AB  - BACKGROUND: The hTAS2R38 taste receptor genotype is related to bitter taste
      perception and thus may affect food preferences. The present study aimed to
      evaluate the relationship between the hTAS2R38 genotype and the food consumption
      and nutrient intakes of Finnish children aged 2-6 years. METHODS: Dietary intake
      was assessed with 7-day food records, and DNA samples were collected by cheek
      swabs for genotyping. Food intake data between the three most common genotypes
      were compared (n = 345). RESULTS: The proportion of the AVI/AVI genotype was
      36.7%; PAV/AVI was 42.4%; and PAV/PAV was 14.9%. Boys with the PAV/PAV genotype
      consumed a mean (SD) weight of sugar and candy of 27 (13) g day(-1), which was
      significantly more compared to the other two genotypes [AVI/AVI 19 (12) g day(-1)
      and PAV/AVI 18 (12) g day(-1); both P < 0.01]. These boys also consumed
      significantly more meat (g day(-1)) compared to AVI/AVI boys (P < 0.05). PAV/PAV
      girls tended to consume more grains (g MJ(-1)) compared to AVI/AVI girls (P =
      0.07). Vegetable and fruit consumption and nutrient intake did not differ
      significantly between genotypes. Based on principal component analysis carried
      out with total food consumption data, PAV/PAV boys were different from both
      AVI/AVI and PAV/AVI boys. CONCLUSIONS: The hTAS2R38 genotype may have distinct
      associations with food consumption in boys and girls.

PMID- 24912559
TI  - False-positive results in metagenomic virus discovery: a strong case for follow
      up diagnosis.
AB  - A viral metagenomic approach using virion enrichment, random amplification and
      next-generation sequencing was used to investigate an undiagnosed cluster of
      dairy cattle presenting with high persistent fever, unresponsive to anti
      microbial and anti-inflammatory treatment, diarrhoea and redness of nose and
      teat. Serum and whole blood samples were taken in the predicted hyperviraemic
      state of an animal that a few days later presented with these clinical signs.
      Bioinformatics analysis of the resulting data from the DNA virus identification
      workflow (a total of 32 757 sequences with average read length 335 bases)
      initially demonstrated the presence of parvovirus-like sequences in the tested
      blood sample. Thorough follow-up using specific real-time RT-PCR assays targeting
      the detected sequence fragments confirmed the presence of these sequences in the
      original sample as well as in a sample of an additional animal, but a
      contamination with an identical genetic signature in negative extraction controls
      was demonstrated. Further investigation using an alternative extraction method
      identified a contamination of the originally used Qiagen extraction columns with
      parvovirus-like nucleic acids or virus particles. Although we did not find any
      relevant virus that could be associated with the disease, these observations
      clearly illustrate the importance of using a proper control strategy and follow
      up diagnostic tests in any viral metagenomic study. 

PMID- 24912560
TI  - Medicare physician payment data: is this transparency?

PMID- 24912561
TI  - Stabilometric assessment of context dependent balance recovery in persons with
      multiple sclerosis: a randomized controlled study.
AB  - BACKGROUND: Balance control relies on accurate perception of visual,
      somatosensory and vestibular cues. Sensory flow is impaired in Multiple Sclerosis
      (MS) and little is known about the ability of the sensory systems to adapt after
      neurological lesions reducing sensory impairment. The aims of the present study
      were to verify whether: 1. Balance rehabilitation administered in a challenging
      sensory conditions would improve stability in upright posture. 2. The improvement
      in a treated sensory condition would transfer to a non treated sensory condition.
      METHODS: Fifty three persons with MS, median (min-max) EDSS score of 5 (2.5-6.5),
      participated in a RCT and were randomly assigned to two groups. The Experimental
      group received balance rehabilitation aimed at improving motor and sensory
      strategies. The Control group received rehabilitation treatment which did not
      include training of sensory strategies. Persons with MS were blindly assessed by
      means of a stabilometric platform with eyes open, eyes closed and dome, on both
      firm surface and foam. Anterior-posterior and medio-lateral sway, velocity of
      sway and the length of Center of Pressure (CoP) trajectory were calculated in the
      six sensory conditions. RESULTS: Experimental group showed statistically
      significant improvement (P < 0.05) in stability in upright posture in eyes closed
      condition on firm surface, and in eyes open, closed, and dome conditions on foam.
      No differences were observed between groups in the eyes open condition on firm
      surface nor in the sensory condition not addressed during the treatment.
      CONCLUSIONS: After rehabilitation people with MS can recover from sensory
      impairments thus improving upright balance. Further, the improvement seems to be
      context-dependent and present just in the treated sensory conditions. TRIAL
      REGISTRATION: ClinicalTrials NCT02131285.

PMID- 24912562
TI  - Robust ferromagnetism in monolayer chromium nitride.
AB  - Design and synthesis of two-dimensional (2D) materials with robust ferromagnetism
      and biocompatibility is highly desirable due to their potential applications in
      spintronics and biodevices. However, the hotly pursued 2D sheets including
      pristine graphene, monolayer BN, and layered transition metal dichalcogenides are
      nonmagnetic or weakly magnetic. Using biomimetic particle swarm optimization
      (PSO) technique combined with ab initio calculations we predict the existence of
      a 2D structure, a monolayer of rocksalt-structured CrN (100) surface, which is
      both ferromagnetic and biocompatible. Its dynamic, thermal and magnetic
      stabilities are confirmed by carrying out a variety of state-of-the-art
      theoretical calculations. Analyses of its band structure and density of states
      reveal that this material is half-metallic, and the origin of the ferromagnetism
      is due to p-d exchange interaction between the Cr and N atoms. We demonstrate
      that the displayed ferromagnetism is robust against thermal and mechanical
      perturbations. The corresponding Curie temperature is about 675 K which is higher
      than that of most previously studied 2D monolayers. 

PMID- 24912563
TI  - Infrared absorption spectra of methylidene radicals in solid neon.
AB  - Infrared absorption lines of methylidene--(12)C(1)H, (13)C(1)H, and (12)C(2)H-
      dispersed in solid neon at 3 K, recorded after photolysis of methane precursors
      with vacuum-ultraviolet light at 121.6 nm, serve as signatures of these trapped
      radicals.

PMID- 24912565
TI  - Opt-outs and upgrades. Ethics and law in the United Kingdom.
AB  - We report on two areas in which UK law and ethics seem out of step with each
      other. 2013 saw the passing of the Human Transplantation (Wales) Bill, which will
      introduce an opt-out system of organ donation in Wales from 2015. In the first
      section, we discuss the convoluted evolution of the Bill and some potential
      problems that we consider may prevent it from achieving its intended goal of
      increasing the number of organs transplanted. The prospect of being able to
      enhance human cognition through cognitive-enhancing drugs ("smart drugs") also
      presents a nexus of questions associated with future ambitions, hopes, and
      concerns as a society. How these drugs might affect the future of work and
      employment is beginning to generate wide public engagement in the UK and forms
      the focus of the second section.

PMID- 24912564
TI  - Long-term adherence with non-invasive ventilation improves prognosis in obese
      COPD patients.
AB  - BACKGROUND AND OBJECTIVE: Long-term non-invasive ventilation (NIV) has become a
      widespread modality of treatment in chronic obstructive pulmonary disease (COPD)
      patients with chronic respiratory failure. However, benefits in terms of patient
      related outcomes are still under debate. Both NIV adherence and heterogeneous
      responses in different COPD phenotypes may contribute to the difficulty of
      demonstrating NIV benefits. Our aim was to assess the impact of NIV adherence on
      the rate of hospitalization for acute exacerbation and death. METHODS: This is a
      prospective multi-centre cohort study of COPD patients treated by long-term NIV.
      Comorbidities, anthropometrics, respiratory parameters were collected at
      inclusion in the study. Follow-up data included vital status, NIV adherence and
      hospitalizations. The influence of NIV adherence on prognosis was tested using an
      adjusted Cox model. Sensitivity analyses for obese and non-obese COPD subtypes
      were also conducted. RESULTS: Two hundred thirteen patients (48% obese) were
      included with 45.5% died during 47.7 [interquartile range = 27.8; 73] months'
      follow-up. Survival was better in obese COPD than non-obese COPD. The use of NIV
      > 9 h/day was associated with an increased risk of death or hospitalization for
      acute exacerbation [HR = 1.6; 95CI: 1.1-2.4]. In obese COPD, this risk described
      a U-shaped curve from >1 to >9 h/day NIV usage with an improvement in prognosis
      when NIV adherence was > 5 h/day [HR = 0.5; 95CI: 0.2-0.9]. CONCLUSIONS:
      Adherence to NIV was associated with better prognosis only in obese COPD. NIV use
      > 9 h/day predicted poor outcomes.

PMID- 24912566
TI  - Chemical nature of boron and nitrogen dopant atoms in graphene strongly
      influences its electronic properties.
AB  - Boron and nitrogen doped graphenes are highly promising materials for
      electrochemical applications, such as energy storage, generation and sensing. The
      doped graphenes can be prepared by a broad variety of chemical approaches. The
      substitution of a carbon atom should induce n-type behavior in the case of
      nitrogen and p-type behavior in the case of boron-doped graphene; however, the
      real situation is more complex. The electrochemical experiments show that boron
      doped graphene prepared by hydroboration reaction exhibits similar properties as
      the nitrogen doped graphene; according to theory, the electrochemical behavior of
      B and N doped graphenes should be opposite. Here we analyze the electronic
      structure of N/B-doped graphene (at ~5% coverage) by theoretical calculations. We
      consider graphene doped by both substitution and addition reactions. The density
      of states (DOS) plots show that graphene doped by substitution of the carbon atom
      by N/B behaves as expected, i.e., as an n/p-doped material. N-doped graphene also
      has a lower value of the workfunction (3.10 eV) with respect to that of the
      pristine graphene (4.31 eV), whereas the workfunction of B-doped graphene is
      increased to the value of 5.57 eV. On the other hand, the workfunctions of
      graphene doped by addition of -NH2 (4.77 eV) and -BH2 (4.54 eV) groups are both
      slightly increased and therefore the chemical nature of the dopant is less
      distinguishable. This shows that mode of doping depends significantly on the
      synthesis method used, as it leads to different types of behaviour, and, in turn,
      different electronic and electrochemical properties of doped graphene, as
      observed in electrocatalytic experiments. This study has a tremendous impact on
      the design of doped graphene systems from the point of view of synthetic
      chemistry. 

PMID- 24912567
TI  - Adaptive synonymous mutations in an experimentally evolved Pseudomonas
      fluorescens population.
AB  - Conventional wisdom holds that synonymous mutations, nucleotide changes that do
      not alter the encoded amino acid, have no detectable effect on phenotype or
      fitness. However, a growing body of evidence from both comparative and
      experimental studies suggests otherwise. Synonymous mutations have been shown to
      impact gene expression, protein folding and fitness, however, direct evidence
      that they can be positively selected, and so contribute to adaptation, is
      lacking. Here we report the recovery of two beneficial synonymous single base
      pair changes that arose spontaneously and independently in an experimentally
      evolved population of Pseudomonas fluorescens. We show experimentally that these
      mutations increase fitness by an amount comparable to non-synonymous mutations
      and that the fitness increases stem from increased gene expression. These results
      provide unequivocal evidence that synonymous mutations can drive adaptive
      evolution and suggest that this class of mutation may be underappreciated as a
      cause of adaptation and evolutionary dynamics. 

PMID- 24912568
TI  - Questionnaire survey about use of an online appointment booking system in one
      large tertiary public hospital outpatient service center in China.
AB  - BACKGROUND: As a part of nationwide healthcare reforms, the Chinese government
      launched web-based appointment systems (WAS) to provide a solution to problems
      around outpatient appointments and services. These have been in place in all
      Chinese public tertiary hospitals since 2009. METHODS: Questionnaires were
      collected from both patients and doctors in one large tertiary public hospital in
      Shanghai, China.Data were analyzed to measure their satisfaction and views about
      the WAS. RESULTS: The 1000 outpatients randomly selected for the survey were
      least satisfied about the waiting time to see a doctor. Even though the WAS
      provided a much more convenient booking method, only 17% of patients used it. Of
      the 197 doctors surveyed, over 90% thought it was necessary to provide
      alternative forms of appointment booking systems for outpatients. However, about
      80% of those doctors who were not associated professors would like to provide an
      'on-the-spot' appointment option, which would lead to longer waits for patients.
      CONCLUSIONS: Patients were least satisfied about the waiting times. To
      effectively reduce appointment-waiting times is therefore an urgent issue.
      Despite the benefits of using the WAS, most patients still registered via the
      usual method of queuing, suggesting that hospitals and health service providers
      should promote and encourage the use of the WAS. Furthermore, Chinese health
      providers need to help doctors to take others' opinions or feedback into
      consideration when treating patients to minimize the gap between patients' and
      doctors' opinions. These findings may provide useful information for both
      practitioners and regulators, and improve recognition of this efficient and
      useful booking system, which may have far-reaching and positive implications for
      China's ongoing reforms.

PMID- 24912569
TI  - An unusual anatomical variation of the superior turbinate: a case report.
AB  - INTRODUCTION: The only anatomical variation of the superior turbinate defined in
      the literature is concha bullosa. Determination of anatomical variations of the
      intranasal structures is important to perform safe endoscopic sinus surgery and
      avoid complications. CASE PRESENTATION: We report a case of an unusual anatomical
      variation of the superior turbinate in a 55-year-old Turkish man with nasal
      obstruction and headache. CONCLUSIONS: Anatomical variations of superior
      turbinate are very rare. Variations of intranasal structures can easily be
      detected with coronal plane paranasal sinus computed tomography.

PMID- 24912570
TI  - Pro-oncogenic function of HIP-55/Drebrin-like (DBNL) through Ser269/Thr291
      phospho-sensor motifs.
AB  - HIP-55 (HPK1-interacting protein of 55 kDa, also named DBNL, SH3P7, and mAbp1) is
      a multidomain adaptor protein that is critical for organ development and the
      immune response. Here, we report the coupling of HIP-55 to cell growth control
      through its 14-3-3-binding phospho-Ser/Thr-sensor sites. Using affinity
      chromatography, we found HIP-55 formed a complex with 14-3-3 proteins, revealing
      a new node in phospho-Ser/Thr-mediated signaling networks. In addition, we
      demonstrated that HIP-55 is required for proper cell growth control. Enforced HIP
      55 expression promoted proliferation, colony formation, migration, and invasion
      of lung cancer cells while silencing of HIP-55 reversed these effects.
      Importantly, HIP-55 was found to be upregulated in lung cancer cell lines and in
      tumor tissues of lung cancer patients. Upregulated HIP-55 was required to promote
      the growth of tumors in a xenograft animal model. However, tumors with
      S269A/T291A-mutated HIP-55, which ablates 14-3-3 binding, exhibited significantly
      reduced sizes, supporting a vital role of the HIP-55/14-3-3 protein interaction
      node in transmitting oncogenic signals. Mechanistically, HIP-55-mediated
      tumorigenesis activity appears to be in part mediated by antagonizing the tumor
      suppressor function of HPK1. Thus, the HIP-55-mediated oncogenic pathway, through
      S269/T291, may be exploited for the development of new therapeutic strategies. 

PMID- 24912571
TI  - Prognosis and response to first-line single and combination therapy in pulmonary
      arterial hypertension.
AB  - OBJECTIVES: To investigate survival, treatment escalation, effects of first-line
      single- and first-line combination therapy and prognostic markers in idiopathic-
      (IPAH), hereditary- (HPAH) and connective tissue disease-associated (CTD-PAH)
      pulmonary arterial hypertension (PAH). DESIGN: Retrospective analysis of medical
      journals from PAH patients at Skane University Hospital 2000-2011. RESULTS: 1-, 2
      and 3-year survival was 87%, 67%, and 54%, respectively, for the entire
      population, but worse (p = 0.003) in CTD-PAH than IPAH/HPAH. After 1, 2 and 3
      years, 58%, 41% and 24% of patients starting on single therapy were alive on
      single therapy. 37.5% of patients on first-line single therapy received escalated
      treatment at first follow-up. First-line combination therapy more greatly
      decreased pulmonary vascular resistance index (PVRI, p = 0.017) than first-line
      single therapy. Only first-line combination therapy improved (p = 0.042) cardiac
      index (CI). Higher mean right atrial pressure (MRAP, p = 0.018), MRAP/CI (p =
      0.021) and WHO functional class (p < 0.001) and lower 6-min walking distance
      (6MWD, p = 0.001) at baseline, and higher PVRI (p = 0.008) and lower 6MWD (p =
      0.004) at follow-up were associated with worse outcome. CONCLUSIONS: We confirm
      improved survival with PAH-targeted therapies. Survival is still poor and early
      treatment escalation frequently needed. First-line combination therapy may more
      potently improve haemodynamics. MRAP/CI may represent a new prognostic marker in
      PAH.

PMID- 24912572
TI  - Histopathology and immunohistochemistry of tissues outside central nervous system
      in bovine rabies.
AB  - We performed a histopathological and immunohistochemical study of tissues outside
      the central nervous system in 48 cases of bovine rabies confirmed by direct
      immunofluorescence and/or immunohistochemistry (IHC) of the central nervous
      system. In the bovines of this study, mononuclear inflammation in all ganglia
      (trigeminal, spinal, stellate, and celiac) and adrenal medulla was observed. This
      injury also occurred in 85 % of neuro-pituitaries in 55 % of pars intermediate
      and 15 % of the pars distalis of pituitary evaluated. IHC was positive in 92.31 %
      of lumbar spinal ganglia, 90.9 % of trigeminal ganglia, stellate ganglia of 41.67
      and 16.67 % of the celiac ganglia. One of the evaluated adrenal (1/17) showed
      strong immunohistochemical labeling in the cytoplasm of pheochromocytes. The
      pituitary IHC was positive in one case in the neurohypophysis (1/20) and in one
      case in the pars intermedia of the adenohypophysis (1/20). Data from this study
      indicate that in suspected cases of rabies, besides the complex pituitary rete
      mirabile and trigeminal ganglion, the evaluation of other ganglia, particularly
      the lumbar spinal, and adrenal may also contribute to the diagnosis and
      understanding of the clinical presentation and pathogenesis of the disease in
      bovines.

PMID- 24912573
TI  - Factors affecting the osteolysis around the components after posterior-stabilized
      total knee replacement arthroplasty.
AB  - PURPOSE: The purpose of the present study was to evaluate factors that affect the
      occurrence of osteolysis through clinical and radiological comparison between a
      patient group in which osteolysis occurred after total knee arthroplasty (TKA)
      and a patient group in which osteolysis did not occur after TKA. METHODS: The
      present study was conducted with 486 knees that had been followed up for at least
      2 years after undergoing a posterior-stabilized TKA. The subjects were divided
      into a group in which osteolysis occurred and a group in which osteolysis did not
      occur and retrospectively compared and analyzed. Knee Society Knee Score and
      Function Score, preoperative and postoperative range of motion (ROM), femoral and
      tibial implant positions, preoperative and postoperative femerotibial angles,
      posterior femoral condylar offset (PCO), level of joint line (JL), and posterior
      tibial slopes were measured and clinically and radiologically compared. RESULTS:
      Osteolysis occurred in 28 knee joints (5.7%). No significant difference was
      observed between the patient group without osteolysis, and the patient group with
      osteolysis was observed in preoperative and postoperative ROM, femoral and tibial
      implant positions, or preoperative and postoperative femerotibial angles. The
      means of preoperative and postoperative differences in PCO and level of JL were
      significantly larger in the patient group with osteolysis than in the patient
      group without osteolysis (p = 0.01, p = 0.007), and regression analyses showed
      that the means of preoperative and postoperative differences in these two
      variables were related with the occurrence of osteolysis (p = 0.021, p = 0.018).
      CONCLUSION: The present study shows that biomechanical changes occurring after
      TKA are related with the occurrence of osteolysis. For clinical relevance,
      surgeons should pay great attention to restore normal anatomical structure as
      much as possible with careful preoperative plans, accurate surgical techniques,
      and selection of appropriate implants. LEVEL OF EVIDENCE: Retrospective
      comparative study, Level III.

PMID- 24912574
TI  - The biomechanical effect of shoulder remplissage combined with Bankart repair for
      the treatment of engaging Hill-Sachs lesions.
AB  - PURPOSE: The purpose of this study was to determine the biomechanical effects of
      the remplissage repair combined with Bankart repair for engaging Hill-Sachs
      lesions on range of motion (ROM), translation, and glenohumeral kinematics.
      METHODS: Six cadaveric shoulders were tested using a custom shoulder testing
      system. ROM, kinematics, and anterior-posterior (AP) and superior-inferior
      glenohumeral translations were quantified at 0 degrees  and 60 degrees 
      glenohumeral abduction. Six conditions were tested: intact, Bankart lesion,
      Bankart with 40 % Hill-Sachs lesion, Bankart repair, Bankart repair with
      remplissage, and remplissage repair alone. RESULTS: Humeral external rotation
      (ER) and total range of motion increased significantly after the creation of the
      Bankart lesion at both 0 degrees  and 60 degrees  abduction. The Bankart repair
      restored ER to intact values at 0 degrees  and 60 degrees  abduction, and the
      addition of the remplissage repair did not significantly alter range of motion
      from the Bankart repair alone. AP translation increased following the creation of
      the Bankart and Hill-Sachs lesions and was restored with the Bankart repair; the
      remplissage did not alter translation from the Bankart repair alone. At maximum
      ER at 60 degrees  abduction, the apex of the humeral head shifted posteriorly and
      inferiorly with remplissage repair. CONCLUSIONS: The addition of the remplissage
      procedure combined with Bankart repair for treatment of large Hill-Sachs lesions
      had no statistically significant effect on ROM or translation, but altered the
      kinematics of the glenohumeral joint. Thus, by addressing the humeral bone defect
      following an anterior shoulder dislocation, the remplissage technique with
      concurrent Bankart repair may be a relatively minimally invasive option for
      converting engaging Hill-Sachs lesions to non-engaging and promoting shoulder
      stability, though further biomechanical and clinical studies are warranted.

PMID- 24912575
TI  - Reliability of hip internal rotation range of motion measurement using a digital
      inclinometer.
AB  - PURPOSE: Assessment of hip internal rotation (IR) is a critical element in the
      evaluation of a painful hip, yet there currently exists no consistent method of
      determining this measurement. The purpose of this study is to report the intra
      rater and inter-rater reliability of active and passive hip IR measurement using
      a digital inclinometer. METHODS: Twenty-five subjects (8 men, 17 women) with
      asymptomatic hip joints, and no known pathology between the ages of 22 and 42
      participated. Two examiners measured hip IR for each subject using a digital
      inclinometer while visually monitoring pelvic motion. Measurements included
      passive IR, active IR, and active IR while internally rotating both legs
      simultaneously. Statistical analysis was performed including intra-rater and
      inter-rater reliability. RESULTS: There was no significant difference in measured
      IR values. Mean range of motion values for all techniques and both examiners
      ranged from 30.7 degrees  to 32.8 degrees . Intra-rater reliability for examiner
      1 ranged from 0.84 to 0.92. Inter-rater reliability ranged from 0.89 to 0.93. Of
      the methods utilized, active IR of a single leg was the most responsive technique
      with a minimal detectable change value of 5.4 degrees . CONCLUSIONS: Clinical
      assessment of hip IR range of motion can be performed efficiently and reliably
      with a digital inclinometer along with visual monitoring of the pelvis for
      unwanted motion. Findings from this study support unilateral active hip IR in a
      seated position as a reliable and responsive technique for obtaining hip IR
      measurements.

PMID- 24912576
TI  - Factors influencing posterior tibial slope and tibial rotation in opening wedge
      high tibial osteotomy.
AB  - PURPOSE: Opening wedge high tibial osteotomy (HTO) is an accepted treatment
      option for medial compartment knee osteoarthritis with associated varus lower
      limb axis in younger, more active patients. A concern with the use of this
      technique is that posterior tibial slope (PTS) and tibial rotation can be
      altered. We hypothesized that there is a tendency to increase the PTS and
      internal rotation of the distal tibia during the procedure and that certain intra
      operative parameters may influence the amount of change that can be expected.
      METHODS: A cadaveric model and surgical navigation system were used to evaluate
      the influence of certain intra-operative factors of the degree of PTS and tibial
      rotation change observed during medial opening HTO. Parameters evaluated
      included: degree of osteotomy opening, knee flexion angle, location of limb
      support (thigh versus foot), performance of a posteromedial release, the status
      of the lateral cortical hinge, and the degree of osteoarthritis present in the
      knee. RESULTS: Combining measurements of all specimens and parameters, a mean PTS
      increase of 2.7 degrees  +/- 3.9 degrees  and a mean tibial internal rotation of
      1.5 degrees  +/- 2.9 degrees  were observed. Clinically, significant changes in
      tibial slope (>2 degrees ) occurred in 50.4 % of corrections, while significant
      changes in tibial rotation (>5 degrees ) occurred in only 11.9 % of corrections.
      Patients with significant osteoarthritis and concomitant flexion contracture,
      cases where large corrections were required, and procedures in which the lateral
      cortical hinge was disrupted were associated with increased PTS change. The other
      factors evaluated did not exert a significant influence of the degree of PTS
      change observed. CONCLUSIONS: Surgeons should be vigilant for possible PTS
      change, particularly in high-risk situations as outlined above. Routine use of an
      intra-operative measure of PTS is recommended to avoid inadvertent slope change.

PMID- 24912577
TI  - Arthroscopic debridement of the pubic symphysis: an experimental study.
AB  - PURPOSE: Open curettage of the symphysis has shown promising results in patients
      with recalcitrant osteitis pubis. However, this has been bedevilled with an
      extended intraoperative morbidity. Aim of this study was to come up with a novel
      arthroscopic debridement of the pubic symphysis and to bring to the fore the
      potential risks of soft tissue damage. METHODS: This study was conducted on six
      human cadavers (mean age 83 years). CT scans were obtained for measurement of the
      symphyseal morphology. Consequent upon these measurements, four different
      potential arthroscopic portals were defined with the intention to gain adequate
      insight and to reach the whole joint space with instruments: one suprapubic
      portal and three anterior portals (antero-superior, antero-central and antero
      inferior). Soft tissue, except for musculotendinous attachments and neurovascular
      structures, was dissected. A two-portal arthroscopic debridement under image
      intensifier control with resection of the symphyseal disc and abrasion of the
      subchondral bone were performed. RESULTS: Considering the narrow joint space,
      small instruments/scope (4.5/2.7 mm) is recommended. Correct portal placement and
      debridement procedure can only be reliably performed under fluoroscopic imaging
      in two radiographic projections (outlet and inlet view) with a mean total
      fluoroscopic time of 15-20 s and a dose area product between 100 and 120 cGy
      cm(2). Two portals have proved beneficial: the suprapubic portal for instruments
      and the antero-central portal for the scope. Other portals had several
      limitations, e.g. potential instrumental conflict (anterior-superior) or damaging
      of neurovascular and other soft tissue structures (anterior-inferior).
      CONCLUSION: With well-defined arthroscopic portals and adherence to basic
      principles of arthroscopic surgery, debridement of the pubic symphysis can be
      performed reproducibly without compromising important anatomical structures. This
      less invasive arthroscopic debridement is a safely applicable procedure and
      therefore might be a reasonable alternative to open curettage. One may assume
      that this technique will lead to a shorter rehabilitation time and will provide a
      successful therapy especially in the treatment of professional athletes in the
      future.

PMID- 24912578
TI  - Liver parenchymal sparing surgery for locally advanced gallbladder cancer with
      extracapsular lymph node invasion.
AB  - A complete R0 resection is the standard treatment in patients with gallbladder
      cancer and the only potentially definitive curative therapy. Major hepatectomy,
      including right or extended right hepatectomy with extrahepatic bile duct
      resection, would be an option in patients with locally advanced gallbladder
      cancer, while morbidity and mortality rate are still high. Herein, we report a
      case of a locally advanced gallbladder cancer invading the right hepatic artery
      (RHA), common hepatic duct, and transverse colon. This patient was successfully
      treated with parenchymal sparing surgery without major hepatectomy and achieved
      R0 resection by means of extended cholecystectomy combined with resection of the
      transverse colon, extrahepatic bile duct, and RHA. Intrahepatic arterial flow was
      preserved without reconstruction of the RHA, and the postoperative course was
      favorable. Liver parenchymal sparing surgery might be an alternative procedure in
      patients with gallbladder cancer, to minimize the risk of severe morbidity, if R0
      resection is possible. 

PMID- 24912579
TI  - Losartan attenuates renal interstitial fibrosis and tubular cell apoptosis in a
      rat model of obstructive nephropathy.
AB  - Ureteral obstruction leads to renal injury and progresses to irreversible renal
      fibrosis, with tubular cell atrophy and apoptosis. There is conflicting evidence
      concerning whether losartan (an angiotensin II type I receptor antagonist)
      mitigates renal interstitial fibrosis and renal tubular epithelial cell apoptosis
      following unilateral ureteral obstruction (UUO) in animal models. The aim of this
      study was to investigate the effect and mechanism of losartan on renal tubular
      cell apoptosis and renal fibrosis in a rat model of UUO. The rats were subjected
      to UUO by ureteral ligation and were treated with dimethyl sulfoxide (control) or
      losartan. The controls underwent sham surgery. The renal tissues were collected
      3, 5, 7 and 14 days after surgery for measurement of various indicators of renal
      fibrosis. UUO increased the expression levels of alpha-smooth muscle actin and
      collagen I, and the extent of renal tubular fibrosis and apoptosis in a time
      dependent manner. Losartan treatment partially attenuated these responses.
      Progression of renal interstitial fibrosis was accompanied by phosphorylation of
      signal transducer and activator of transcription 3 (STAT3) and altered the
      expression levels of two apoptosis-related proteins (Bax and Bcl2). Losartan
      treatment also partially attenuated these responses. The results indicated that
      losartan attenuated renal fibrosis and renal tubular cell apoptosis in a rat
      model of UUO. This effect appeared to be mediated by partial blockage of STAT3
      phosphorylation. 

PMID- 24912580
TI  - How is shrimp aquaculture transforming coastal livelihoods and lagoons in Estero
      Real, Nicaragua? The need to integrate social-ecological research and ecosystem
      based approaches.
AB  - Ecosystem-based approaches to aquaculture integrate environmental concerns into
      planning. Social-ecological systems research can improve this approach by
      explicitly relating ecological and social dynamics of change at multiple scales.
      Doing so requires not only addressing direct effects of aquaculture but also
      considering indirect factors such as changes in livelihood strategies, governance
      dynamics, and power relations. We selected the community of Puerto Morazan,
      Nicaragua as a case study to demonstrate how the introduction of small-scale
      aquaculture radically transformed another key livelihood activity, lagoon shrimp
      fishing, and the effects that these changes have had on lagoons and the people
      that depend on them. We find that shrimp aquaculture played a key role in the
      collapse, in the 1990s, of an existing lagoon common-property management. Shrimp
      aquaculture-related capital enabled the adoption of a new fishing technique that
      not only degraded lagoons but also led to their gradual privatization. The
      existence of social ties between small-scale shrimp farmers and other community
      members mitigated the impacts of privatization, illustrating the importance of
      social capital. Since 2008, community members are seeking to communally manage
      the lagoons once again, in response to degraded environmental conditions and a
      consolidation of the shrimp industry at the expense of smaller actors. This
      research shows that shrimp aquaculture intersects with a complex set of drivers,
      affecting not only how ecosystems are managed but also how they are perceived and
      valued. Understanding these social-ecological dynamics is essential to implement
      realistic policies and management of mangrove ecosystems and address the needs of
      resource-dependent people. 

PMID- 24912581
TI  - A randomized study of the effect of carbonated water prior to myocardial SPECT.
AB  - OBJECTIVE: In myocardial perfusion single-photon emission computed tomography
      (SPECT), abdominal activity often interferes with the evaluation of perfusion in
      the inferior wall, especially after pharmacological stress. In this randomized
      study, we examined the effect of carbonated water intake versus still water
      intake on the quality of images obtained during myocardial perfusion images (MPI)
      studies. METHODS: A total of 467 MIBI studies were randomized into a carbonated
      water group and a water group. The presence of intestinal activity adjacent to
      the inferior wall was evaluated by two observers. Furthermore, a semi
      quantitative analysis was performed in the adenosine subgroup, using a count
      ratio of the inferior myocardial wall and adjacent abdominal activity. RESULTS:
      The need for repeated SPECT in the adenosine studies was 5.3% in the carbonated
      water group versus 19.4% in the still water group (p = 0.019). The inferior wall
      to-abdomen count ratio was significantly higher in the carbonated water group
      compared to the still water group (2.11 +/- 1.00 vs. 1.72 +/- 0.73, p < 0.001).
      The effect of carbonated water during rest and after exercise was not
      significant. CONCLUSIONS: This randomized study showed that carbonated water
      significantly reduced the interference of extra-cardiac activity in adenosine
      SPECT MPI.

PMID- 24912583
TI  - Gene co-expression network analysis identifies porcine genes associated with
      variation in Salmonella shedding.
AB  - BACKGROUND: Salmonella enterica serovar Typhimurium is a gram-negative bacterium
      that can colonise the gut of humans and several species of food producing farm
      animals to cause enteric or septicaemic salmonellosis. While many studies have
      looked into the host genetic response to Salmonella infection, relatively few
      have used correlation of shedding traits with gene expression patterns to
      identify genes whose variable expression among different individuals may be
      associated with differences in Salmonella clearance and resistance. Here, we
      aimed to identify porcine genes and gene co-expression networks that
      differentiate distinct responses to Salmonella challenge with respect to faecal
      Salmonella shedding. RESULTS: Peripheral blood transcriptome profiles from 16
      pigs belonging to extremes of the trait of faecal Salmonella shedding counts
      recorded up to 20 days post-inoculation (low shedders (LS), n = 8; persistent
      shedders (PS), n = 8) were generated using RNA-sequencing from samples collected
      just before (day 0) and two days after (day 2) Salmonella inoculation. Weighted
      gene co-expression network analysis (WGCNA) of day 0 samples identified four
      modules of co-expressed genes significantly correlated with Salmonella shedding
      counts upon future challenge. Two of those modules consisted largely of innate
      immunity related genes, many of which were significantly up-regulated at day 2
      post-inoculation. The connectivity at both days and the mean gene-wise expression
      levels at day 0 of the genes within these modules were higher in networks
      constructed using LS samples alone than those using PS alone. Genes within these
      modules include those previously reported to be involved in Salmonella resistance
      such as SLC11A1 (formerly NRAMP1), TLR4, CD14 and CCR1 and those for which an
      association with Salmonella is novel, for example, SIGLEC5, IGSF6 and TNFSF13B.
      CONCLUSIONS: Our analysis integrates gene co-expression network analysis, gene
      trait correlations and differential expression to provide new candidate
      regulators of Salmonella shedding in pigs. The comparatively higher expression
      (also confirmed in an independent dataset) and the significantly higher
      connectivity of genes within the Salmonella shedding associated modules in LS
      compared to PS even before Salmonella challenge may be factors that contribute to
      the decreased faecal Salmonella shedding observed in LS following challenge.

PMID- 24912584
TI  - Differences in neural circuitry guiding behavioral responses to polarized light
      presented to either the dorsal or ventral retina in Drosophila.
AB  - Linearly polarized light (POL) serves as an important cue for many animals,
      providing navigational information, as well as directing them toward food sources
      and reproduction sites. Many insects detect the celestial polarization pattern,
      or the linearly polarized reflections off of surfaces, such as water. Much
      progress has been made toward characterizing both retinal detectors and
      downstream circuit elements responsible for celestial POL vision in different
      insect species, yet much less is known about the neural basis of how polarized
      reflections are detected. We previously established a novel, fully automated
      behavioral assay for studying the spontaneous orientation response of Drosophila
      melanogaster populations to POL stimuli presented to either the dorsal, or the
      ventral halves of the retina. We identified separate retinal detectors mediating
      these responses: the 'Dorsal Rim Area' (DRA), which had long been implicated in
      celestial POL vision, as well as a previously uncharacterized 'ventral
      polarization area' (VPA). In this study, we investigate whether DRA and VPA use
      the same or different downstream circuitry, for mediating spontaneous behavioral
      responses. We use homozygous mutants, or molecular genetic circuit-breaking tools
      (silencing, as well as rescue of synaptic activity), in combination with our
      behavioral paradigm. We show that responses to dorsal versus ventral stimulation
      involve previously characterized optic lobe neurons, like lamina monopolar cell
      L2 and medulla cell types Dm8/Tm5c. However, using different experimental
      conditions, we show that important differences exist between the requirement of
      these cell types downstream of DRA versus VPA. Therefore, while the neural
      circuits underlying behavioral responses to celestial and reflected POL cues
      share important building blocks, these elements play different functional roles
      within the network.

PMID- 24912585
TI  - Overexpression of Tiam1 is associated with malignant phenotypes of nasopharyngeal
      carcinoma.
AB  - The aim of the present study was to analyze the roles of T lymphoma invasion and
      metastasis 1 (Tiam1) in nasopharyngeal carcinoma (NPC) progression and its
      correlation with clinicopathological features, including the survival of patients
      with NPC. Tiam1 protein expression in NPC tissues was examined using
      immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR)
      and immunofluorescence staining were performed to detect the expression of Tiam1
      in 6 NPC cell lines. Stable Tiam1-overexpressing NPC cells using a transfection
      technique and Tiam1-silencing NPC cells using short hairpin RNA were constructed.
      Subsequently, MTT assay, plate and soft agar colony formation assays, cell
      adhesion, migration, invasion assays and experimental animal models were carried
      out to detect the biological functions of Tiam1 in vitro and in vivo.
      Immunohistochemical analysis revealed that Tiam1 had high expression in 96 of 140
      (68.6%) paraffin-embedded archival NPC biopsies. Tiam1 overexpression was
      significantly associated with N classification (P=0.004), distant metastasis
      (P=0.042) and clinical stage (P=0.042). Patients with higher levels of Tiam1
      expression had poorer overall survival (P=0.002). Multivariate analysis revealed
      that Tiam1 expression is an independent prognostic indicator for the overall
      survival of NPC patients. Using the approaches of exogenous overexpression and
      the knockdown of Tiam1 expression, respectively, it was confirmed that Tiam1
      promoted cell proliferation, adhesion, invasion and migration in vitro and in
      vivo. These data support the notion that Tiam1 plays an important role in the
      progression of NPC, and the overexpression of Tiam1 is associated with malignant
      phenotypes of NPC.

PMID- 24912586
TI  - A non-synonymous polymorphism in IL-23R Gene (rs1884444) is associated with
      reduced risk to schistosomiasis-associated Immune Reconstitution Inflammatory
      Syndrome in a Kenyan population.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) and Schistosomiasis co-infection
      is common among residents at the shores of Lake Victoria in Kenya. About 36% of
      this population initiating antiretroviral therapy (ART) experience Immune
      Reconstitution Inflammatory Syndrome (IRIS) that complicates recovery. Several IL
      23R alleles have been associated with susceptibility to both autoimmune and
      inflammatory diseases through T-helper type 17 (TH17) cells. However, whether or
      not variants within the IL-23R increase susceptibility to IRIS in western Kenya
      is unknown. The objective of the current study was to determine the association
      between IL-23R gene polymorphisms, CD4+ cell counts and HIV RNA levels and IRIS
      in HIV and Schistosoma mansoni co-infected patients undergoing highly active anti
      retroviral therapy (HAART). METHODS: A three-month case-control study was
      conducted on antiretroviral naive schistosomiasis/HIV co-infected fishermen
      starting HAART in Uyoma Rarieda, Siaya County, Kenya. Seventy one patients were
      sampled at baseline and followed up for three months, to establish if they
      developed Schistosoma-related IRIS. In addition, the CD4+ cell counts and HIV RNA
      levels were determined in pre- and post-administration of HAART. Variations at
      five polymorphic sites of IL-23R (rs1884444, rs11465754, rs6682925, rs7530511 and
      rs7539625) based on >10% minor allele frequency in Yoruban reference population
      was determined using Allelic Discrimination Assay. The association between the
      five variants and susceptibility to IRIS was determined using logistic regression
      while controlling for potential confounders. In addition, the functional
      differences between the baseline CD4 + Cell counts and viral loads were
      determined using medians while across IL-23R genotypes were determined using
      Kruskal-Wallis tests. RESULTS: Overall, 26 (36.6%) patients developed
      schistosomiasis-associated IRIS at a median age of 35.5 years. Carriage of the TT
      genotype at the non-synonymous rs1884444 T > G relative to GG, was associated
      with a decreased risk of schistosomiasis-associated IRIS (OR, 0.25, 95% CI, 0.07
      0.96, P = 0.043) while both baseline CD4+ cell counts and viral loads had no
      association with IRIS. CONCLUSION: These findings indicate that the non
      synonymous variant rs1884444 T > G of IL-23R is associated with a decreased risk
      to schistosomiasis-associated IRIS. However, additional studies in a larger
      cohort and with an all inclusive polymorphic variants in the synonymous and non
      synonymous regions need to be evaluated.

PMID- 24912587
TI  - Satisfaction with healthcare services among free clinic patients.
AB  - Free clinics provide free or reduced fee health services to the un- or under
      insured. Patient engagement is important to understand patients' needs and to
      improve healthcare systems. There are few studies that examined patient
      engagement and satisfaction among the underserved and how patients perceive the
      quality of healthcare services in a free clinic setting. This study examined free
      clinic patients' satisfaction in order to better understand how free clinic
      patients perceive quality of healthcare services. English or Spanish speaking
      patients (N = 351), aged 18 years or older completed a self-administered survey
      using standardized measures of patient satisfaction and health status. Additional
      questions of patient satisfaction and experience with healthcare which fit a free
      clinic setting were developed. While the satisfaction with interpreter services
      was overall high, there were potential issues of a family member as an
      interpreter and unmet needs for interpreter services. Participants reported
      different levels of patient satisfaction by three language categories: native
      English speakers, non-native English speakers, and Spanish speakers. Health
      status is an important indicator to determine patient satisfaction. To improve
      patient satisfaction and engagement among free clinic patients, factors such as:
      quality of a family interpreter, unmet needs for interpreter services, social
      support, and health education programs may need to be considered. The differences
      in these three language groups indicate that not all free clinic patients may be
      combined together into a general category of free clinic patients. It may be
      necessary to provide customized treatment for each of these groups.

PMID- 24912588
TI  - Improving cord blood unit quantity and quality at King Abdullah International
      Medical Research Center Cord Blood Bank.
AB  - BACKGROUND: Public cord blood banks (CBBs) store cord blood unit (CBU) donations
      for anyone in need. However, strict regulations need to be followed to build up
      high-quality bank products that can be used worldwide. We established a public
      CBB at a tertiary hospital in Saudi Arabia. Here, we investigated the reasons
      behind rejecting or not collecting CBUs over 2 years (2011-2012) and which steps
      were implemented to improve the number and quality of storable units. STUDY
      DESIGN AND METHODS: A total of 2891 mothers were evaluated. Reasons for rejecting
      donors, not collecting, and rejecting units before or after collection were
      analyzed and compared for the years 2011 and 2012. RESULTS: A total of 1157 (40%)
      CBUs were not collected, mainly due to staff availability, and 564 (20%) CBUs
      were rejected. The main reason for rejecting donations was the mother's or
      neonate's health. Rejecting CBUs after collection was due to low volume. A total
      of 1170 (40%) CBUs were successfully collected for potential banking and sent for
      processing; however, 58% were rejected in the laboratory due to low total
      nucleated cell counts. Several changes were implemented during the 2 years
      including physician education and awareness, in utero collection, cesarean
      collection, and staff recruitment. These changes positively affected the numbers
      of our collected units. Out of the initially eligible mothers in 2011, only 17%
      were banked; this was increased to 33% in 2012. CONCLUSIONS: We identified the
      problems with collecting CBUs for banking and will keep improving our selection
      process of recruiting more CBUs of high quality.

PMID- 24912589
TI  - Effect of screening and lifestyle counselling on incidence of ischaemic heart
      disease in general population: Inter99 randomised trial.
AB  - OBJECTIVE: To investigate the effect of systematic screening for risk factors for
      ischaemic heart disease followed by repeated lifestyle counselling on the 10 year
      development of ischaemic heart disease at a population level. DESIGN: Randomised
      controlled community based trial. SETTING: Suburbs of Copenhagen, Denmark.
      PARTICIPANTS: 59,616 people aged 30-60 years randomised with different age and
      sex randomisation ratios to an intervention group (n = 11,629) and a control
      group (n = 47,987). INTERVENTION: The intervention group was invited for
      screening, risk assessment, and lifestyle counselling up to four times over a
      five year period. All participants with an unhealthy lifestyle had individually
      tailored lifestyle counselling at all visits (at baseline and after one and three
      years); those at high risk of ischaemic heart disease, according to predefined
      criteria, were furthermore offered six sessions of group based lifestyle
      counselling on smoking cessation, diet, and physical activity. After five years
      all were invited for a final counselling session. Participants were referred to
      their general practitioner for medical treatment, if relevant. The control group
      was not invited for screening. MAIN OUTCOME MEASURES: The primary outcome measure
      was incidence of ischaemic heart disease in the intervention group compared with
      the control group. Secondary outcome measures were stroke, combined events
      (ischaemic heart disease, stroke, or both), and mortality. RESULTS: 6091 (52.4%)
      people in the intervention group participated at baseline. Among 5978 people
      eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%)
      attended. A total of 3163 people died in the 10 year follow-up period. Among
      58,308 without a history of ischaemic heart disease at baseline, 2782 developed
      ischaemic heart disease. Among 58,940 without a history of stroke at baseline,
      1726 developed stroke. No significant difference was seen between the
      intervention and control groups in the primary end point (hazard ratio for
      ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the
      secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to
      1.09; total mortality 1.00, 0.91 to 1.09). CONCLUSION: A community based,
      individually tailored intervention programme with screening for risk of ischaemic
      heart disease and repeated lifestyle intervention over five years had no effect
      on ischaemic heart disease, stroke, or mortality at the population level after 10
      years.Trial registration Clinical trials NCT00289237.

PMID- 24912590
TI  - A comparison of N-glycan profiles in human plasma and vitreous fluid.
AB  - PURPOSE: To investigate the concentration and composition of N-glycans in plasma
      and vitreous samples obtained from patients with non-proliferative vitreoretinal
      diseases. METHODS: Plasma and vitreous samples were collected from 11 patients
      with idiopathic macular hole (MH) and 9 patients with epiretinal membrane (ERM).
      The samples were pretreated for enzymatic cleaving, and subsequently glycans
      released from proteins were captured on BlotGlyco H beads. Sialic acids were
      methyl-esterified. Processed glycans were tagged with aminooxy-functionalized
      peptide reagent (aoWR) and released from the beads, followed by detection by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). The concentration and composition of N-glycans in the samples
      were assessed. RESULTS: Concentration of N-glycans in vitreous samples (132 +/-
      29 pmol/100 MUg protein) was significantly lower compared with those in plasma
      samples (714 +/- 29 pmol/100 MUg protein, p < 0.001). Predominant N-glycan in
      both plasma (39.7 +/- 1.1 %) and vitreous fluid (37.2 +/- 3.1 %) was identical,
      and the composition was presumed as [(Hex)2(HexNAc)2(NeuAc)2+ (Man)3(GlcNAc)2].
      By contrast, the second-ranked N-glycan in vitreous samples (15.6 +/- 1.5 %) was
      the seventh in plasma (2.3 +/- 0.2 %). CONCLUSIONS: The current data provide
      useful information on N-glycan profile in the vitreous fluid, which is distinct
      from that in the plasma.

PMID- 24912591
TI  - On the large sigma-hyperconjugation in alkanes and alkenes.
AB  - The conventional view that the sigmaCC and sigmaCH bonds in alkanes and
      unsaturated hydrocarbons are so highly localized that their non-steric
      interactions are negligible is scrutinized by the block-localized wavefunction
      (BLW) method. Even molecules considered conventionally to be "strain free" and
      "unperturbed" have surprisingly large and quite significant total sigma-BLW
      delocalization energies (DEs) due to their geminal and vicinal hyperconjugative
      interactions. Thus, the computed BLW-DEs (in kcal mol(-1)) for the antiperiplanar
      conformations of the n-alkanes (C(N)H(2N+2), N = 1-10) range from 11.6 for ethane
      to 82.2 for n-decane and are 50.9 for cyclohexane and 91.0 for adamantane.
      Although sigma-electron delocalization in unsaturated hydrocarbons usually is
      ignored, the sigma-BLW-DEs (in kcal mol(-1)) are substantial, as exemplified by
      D2h ethylene (9.0), triplet D2d ethylene (16.4), allene (19.3), butadiene (19.0),
      hexatriene (28.3), benzene (28.1), and cyclobutadiene (21.1). While each
      individual geminal and vicinal hyperconjugative interaction between hydrocarbon
      sigma-bonding and sigma-antibonding orbitals tends to be smaller than an
      individual pi conjugative interaction (e.g., 10.2 kcal mol(-1) in anti-1,3
      butadiene, the presence of many sigma-hyperconjugative interactions (e.g., a
      total of 12 in anti-1,3-butadiene, see text), result in substantial total sigma
      stabilization energies (e.g., 19.0 kcal mol(-1) for butadiene), which may surpass
      those from the pi interactions. Although large in magnitude, sigma-electron
      delocalization energies often are obscured by cancellation when two hydrocarbons
      are compared. Rather than being strain-free, cyclohexane, adamantane, and
      diamantane suffer from their increasing number of intramolecular 1,4-C...C
      repulsions resulting in elongated C-C bond lengths and reduced sigma
      hyperconjugation, compared to the (skew-free) antiperiplanar n-alkane conformers.
      Instead of being inconsequential, sigma-bond interactions are important and merit
      consideration.

PMID- 24912592
TI  - Aromaticity of azines through dyotropic double hydrogen transfer reaction.
AB  - Density functional theory calculations have been performed at B3LYP/6-31+G (d)
      level to quantify the aromaticities of mono- to triazines through dyotropic
      double hydrogen transfer (DDHT) reaction. The reaction was chosen such that the
      azines are products of double hydrogen dyotropic rearrangement, and activation
      barriers and energies of the reactions were functions of the aromaticities of
      azines. Small activation barriers and high energies of reactions were
      characteristic of the reactions delivering highly aromatic azines. Synchronicity,
      reaction energies and energies of activation have been analyzed, and the
      aromaticity values obtained thereof were compared with the aromaticity values
      from other geometric and magnetic criteria. Energies of activation were found
      superior to the energies of reaction for the determination of the aromaticities.
      Aromaticities of most of the azines were comparable to the aromaticity of
      benzene. Activation barriers and reaction energies for the dyotropic reactions
      delivering contiguous or polynitrogeneous azines had thermodynamic contributions
      arising from the contiguous nature of azines, in addition to the aromaticity
      related thermodynamic contributions. Moreover, the aromaticity values of azines
      are also affected by the fusion of azine to the reaction center. When corrected
      for these factors, the aromaticities of azines using energies of activation for
      DDHT correlated nicely with the aromaticities of azines reported in the
      literature through NICS(0)pizz and some other energetic methods.

PMID- 24912593
TI  - Computational evaluation of factors governing catalytic 2-keto acid
      decarboxylation.
AB  - Recent advances in computational approaches for creating pathways for novel
      biochemical reactions has motivated the development of approaches for identifying
      enzyme-substrate pairs that are attractive candidates for effecting catalysis. We
      present an improved structural-based strategy to probe and study enzyme-substrate
      binding based on binding geometry, energy, and molecule characteristics, which
      allows for in silico screening of structural features that imbue higher catalytic
      potential with specific substrates. The strategy is demonstrated using 2-keto
      acid decarboxylation with various pairs of 2-keto acids and enzymes. We show that
      this approach fitted experimental values for a wide range of 2-keto acid
      decarboxylases for different 2-keto acid substrates. In addition, we show that
      the structure-based methods can be used to select specific enzymes that may be
      promising candidates to catalyze decarboxylation of certain 2-keto acids. The key
      features and principles of the candidate enzymes evaluated by the strategy can be
      used to design novel biosynthesis pathways, to guide enzymatic mutation or to
      guide biomimetic catalyst design. 

PMID- 24912594
TI  - Theoretical study (CC2, DFT and PCM) of charge transfer complexes between
      antithyroid thioamides and TCNE: electronic CT transitions.
AB  - A set of representative DFT and wavefunction based theoretical approaches have
      been used to study ionization potentials and, predominantly, electronic charge
      transfer transitions in the complexes formed between TCNE as an electron acceptor
      and both mono and bicyclic thioamides as donors. The mentioned thioamides are of
      pharmacological importance due to their efficient antithyroid activity. Within a
      few kcal mol(-1) we have found six stable conformers for complexes with each of
      benzothioamides and four conformers for each of monocyclic thioamides. Present
      theoretical study satisfactorily shows that there is a good correspondence
      between the CC2/Def2-TZVPP calculated excitation energies for complexes in vacuum
      supplemented by the DFT solvent shifts and experiment. Present theoretical study
      contributes to deeper understanding of the electronic nature of the ground and
      excited states of the complexes with antithyroid activity. 

PMID- 24912595
TI  - Cellular mechanisms underlying the increased disease severity seen for patients
      with long QT syndrome caused by compound mutations in KCNQ1.
AB  - The KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) gene
      encodes the Kv7.1 potassium channel which forms a complex with KCNE1 (potassium
      voltage-gated channel Isk-related family member 1) in the human heart to produce
      the repolarizing IKs (slow delayed rectifier potassium current). Mutations in
      KCNQ1 can perturb IKs function and cause LQT1 (long QT syndrome type 1). In LQT1,
      compound mutations are relatively common and are associated with increased
      disease severity. LQT1 compound mutations have been shown to increase channel
      dysfunction, but whether other disease mechanisms, such as defective channel
      trafficking, contribute to the increase in arrhythmic risk has not been
      determined. Using an imaging-based assay we investigated the effects of four
      compound heterozygous mutations (V310I/R594Q, A341V/P127T, T391I/Q530X and
      A525T/R518X), one homozygous mutation (W248F) and one novel compound heterozygous
      mutation (A178T/K422fs39X) (where fs denotes frameshift) on channel trafficking.
      By analysing the effects in the equivalent of a homozygous, heterozygous and
      compound heterozygous condition, we identify three different types of behaviour.
      A341V/P127T and W248F/W248F had no effect, whereas V310I/R594Q had a moderate,
      but not compound, effect on channel trafficking. In contrast, T391I/Q530X,
      A525T/R518X and A178T/K422fs39X severely disrupted channel trafficking when
      expressed in compound form. In conclusion, we have characterized the disease
      mechanisms for six LQT1 compound mutations and report that, for four of these,
      defective channel trafficking underlies the severe clinical phenotype. 

PMID- 24912596
TI  - High-pressure structural behaviour of HoVO4: combined XRD experiments and ab
      initio calculations.
AB  - We report a high-pressure experimental and theoretical investigation of the
      structural properties of zircon-type HoVO4. Angle-dispersive x-ray diffraction
      measurements were carried out under quasi-hydrostatic and partial non-hydrostatic
      conditions up to 28 and 23.7 GPa, respectively. In the first case, an
      irreversible phase transition is found at 8.2 GPa. In the second case, the onset
      of the transition is detected at 4.5 GPa, a second (reversible) transition is
      found at 20.4 GPa, and a partial decomposition of HoVO4 was observed. The
      structures of the different phases have been assigned and their equations of
      state (EOS) determined. Experimental results have also been compared to
      theoretical calculations which fully agree with quasi-hydrostatic experiments.
      Theory also suggests the possibility of another phase transition at 32 GPa; i.e.
      beyond the pressure limit covered by present experiments. Furthermore,
      calculations show that deviatoric stresses could trigger the transition found at
      20.4 GPa under non-hydrostatic conditions. The reliability of the present
      experimental and theoretical results is supported by the consistency between the
      values yielded for transition pressures and EOS parameters by the two methods.

PMID- 24912597
TI  - Health insurance and chronic conditions in low-income urban whites.
AB  - Little is known about how health insurance contributes to the prevalence of
      chronic disease in the overlooked population of low-income urban whites. This
      study uses cross-sectional data on 491 low-income urban non-elderly non-Hispanic
      whites from the Exploring Health Disparities in Integrated Communities-Southwest
      Baltimore (EHDIC-SWB) study to examine the relationship between insurance status
      and chronic conditions (defined as participant report of ever being told by a
      doctor they had hypertension, diabetes, stroke, heart attack, anxiety or
      depression, asthma or emphysema, or cancer). In this sample, 45.8 % were
      uninsured, 28.3 % were publicly insured, and 25.9 % had private insurance.
      Insured participants had similar odds of having any chronic condition (odds
      ratios (OR) 1.06; 95 % confidence intervals (CI) 0.70-1.62) compared to uninsured
      participants. However, those who had public insurance had a higher odds of
      reporting any chronic condition compared to the privately insured (OR 2.29; 95 %
      CI 1.21-4.35). In low-income urban areas, the health of whites is not often
      considered. However, this is a significant population whose reported prevalence
      of chronic conditions has implications for the Medicaid expansion and the
      implementation of health insurance exchanges. 

PMID- 24912598
TI  - Neighborhood stressors, mastery, and depressive symptoms: racial and ethnic
      differences in an ecological model of the stress process in Chicago.
AB  - Neighborhood stressors are associated with depressive symptoms and are more
      likely to be experienced in poor, non-White neighborhoods. Neighborhood stress
      process theory suggests that neighborhood stressor affect mental health through
      personal coping resources, such as mastery. Mastery is thought to be both a
      pathway and a buffer of the ill effects of neighborhood stressors. This research
      examines the neighborhood stress process with a focus on racial and ethnic
      differences in the relationship between neighborhood stressors, mastery, and
      depressive symptoms in a multi-ethnic sample of Chicago residents. Findings
      suggest race-specific effects on depressive symptoms. Mastery is found to be a
      pathway from neighborhood stressors to depressive symptoms but not a buffer
      against neighborhood stressors. Mastery is most beneficial to Whites and those
      living in low stress neighborhoods. 

PMID- 24912600
TI  - Translational read-through as an alternative approach for ocular gene therapy of
      retinal dystrophies caused by in-frame nonsense mutations.
AB  - The eye has become an excellent target for gene therapy, and gene augmentation
      therapy of inherited retinal disorders has made major progress in recent years.
      Nevertheless, a recent study indicated that gene augmentation intervention might
      not stop the progression of retinal degeneration in patients. In addition, for
      many genes, viral-mediated gene augmentation is currently not feasible due to
      gene size and limited packaging capacity of viral vectors as well as expression
      of various heterogeneous isoforms of the target gene. Thus, alternative gene
      based strategies to stop or delay the retinal degeneration are necessary. This
      review focuses on an alternative pharmacologic treatment strategy based on the
      usage of translational read-through inducing drugs (TRIDs) such as PTC124,
      aminoglycoside antibiotics, and designer aminoglycosides for overreading in-frame
      nonsense mutations. This strategy has emerged as an option for up to 30-50% of
      all cases of recessive hereditary retinal dystrophies. In-frame nonsense
      mutations are single-nucleotide alterations within the gene coding sequence
      resulting in a premature stop codon. Consequently, translation of such mutated
      genes leads to the synthesis of truncated proteins, which are unable to fulfill
      their physiologic functions. In this context, application of TRIDs facilitates
      the recoding of the premature termination codon into a sense codon, thus
      restoring syntheses of full-length proteins. So far, clinical trials for non
      ocular diseases have been initiated for diverse TRIDs. Although the clinical
      outcome is not analyzed in detail, an excellent safety profile, namely for
      PTC124, was clearly demonstrated. Moreover, recent data demonstrated sustained
      read-through efficacies of nonsense mutations causing retinal degeneration, as
      manifested in the human Usher syndrome. In addition, a strong retinal
      biocompatibility for PTC124 and designer aminoglycosides has been demonstrated.
      In conclusion, recent progress emphasizes the potential of TRIDs as an
      alternative pharmacologic treatment strategy for treating nonsense mutation-based
      retinal disorders. 

PMID- 24912601
TI  - Re: The measurement of visual acuity in children: an evidence-based update.

PMID- 24912599
TI  - Breast cancer treatment among African American women in north St. Louis,
      Missouri.
AB  - Similar to disparities seen at the national and state levels, African American
      women in St. Louis, Missouri have higher breast cancer mortality rates than their
      Caucasian counterparts. We examined breast cancer treatment (regimens and timing)
      in a sample of African American breast cancer patients diagnosed between 2000 and
      2008 while residing in a North St. Louis cluster (eight zip codes) of late stage
      at diagnosis. Data were obtained from medical record extractions of women
      participating in a mixed-method study of breast cancer treatment experiences. The
      median time between diagnosis and initiation of treatment was 27 days; 12.2% of
      the women had treatment delay over 60 days. These findings suggest that treatment
      delay and regimens are unlikely contributors to excess mortality rates for
      African American women diagnosed in early stages. Conflicting research findings
      on treatment delay may result from the inconsistent definitions of treatment
      delay and variations among study populations. Breast cancer treatment delay may
      reduce breast cancer survival; additional research is needed to better understand
      the points at which delays are most likely to occur and develop policies,
      programs, and interventions to address disparities in treatment delay. There may
      also be differences in treatment-related survivorship quality of life;
      approximately 54% of the women in this sample treated with mastectomies received
      breast reconstruction surgery. Despite the high reconstruction rates, most women
      did not receive definitive completion. African American women have higher
      reconstruction complication rates than Caucasian women; these data provide
      additional evidence to suggest a disparity in breast reconstruction outcomes by
      race.

PMID- 24912603
TI  - Muscle involvement in Dent disease 2.
AB  - BACKGROUND: Dent disease, an X-linked recessive renal tubulopathy, is caused by
      mutations in either CLCN5 (Dent disease 1) or OCRL (Dent disease 2). OCRL
      mutations can also cause Lowe syndrome. In some cases it is difficult to
      differentiate Dent disease 1 and 2 on the basis of clinical features only without
      genetic tests. Several studies have shown differences in serum levels of muscle
      enzymes between these diseases. The aim of our study was to test the validity of
      these findings. METHODS: In total, 23 patients with Dent disease 1 (Group A),
      five patients with Dent disease 2 (Group B) and 19 patients with Lowe syndrome
      (Group C) were enrolled in our study. The serum levels of three muscle enzymes
      [creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate
      aminotransferase (AST)], were measured. The levels of a hepatic enzyme, alanine
      aminotransferase (ALT), were also measured as a control. RESULTS: One patient in
      Group B had muscle hypoplasia of both upper extremities. The serum levels of all
      three muscle enzymes assayed were higher in Group B or C patients than in Group A
      patients. Serum ALT levels were normal in all three groups of patients.
      CONCLUSIONS: The serum levels of muscle enzymes in patients with Dent disease can
      be used as a biomarker to predict genotypes, even though the patients do not have
      clinical symptoms of muscle involvement.

PMID- 24912604
TI  - Biopsy timing and Oxford classification variables in childhood/adolescent IgA
      nephropathy.
AB  - BACKGROUND: Although the Oxford classification of IgA nephropathy appears valid,
      we found crescents were significantly related to renal outcome in our cohort,
      whereas segmental glomerulosclerosis (S) was not. The timing of renal biopsy may
      significantly affect the variables in the Oxford classification. METHOD: The
      relationship between biopsy timing and pathological variables (mesangial
      hypercellularity score [M], endocapillary hypercellularity [E], S, tubular
      atrophy/interstitial fibrosis [T], crescents, and global glomerulosclerosis [G])
      was analyzed retrospectively in 250 children with IgA nephropathy. RESULTS: The
      median time from disease onset to renal biopsy was 5.1 months (interquartile
      range, 2.7-15.4). M (rho = -0.26, P < 0.0001), E (rho = -0.34, P < 0.0001), and
      crescents (rho = -0.14, P = 0.023) showed significant negative correlations, and
      S (rho = 0.15, P = 0.018) and G (rho = 0.25, P < 0.0001) showed significant
      positive correlations with time to biopsy (Spearman test). M, E, and crescents
      differed significantly in renal biopsies obtained before and after 3 years from
      onset (Wilcoxon test). Most crescents (92.9 %) were cellular/fibrocellular and
      were acute lesions. As crescents formed early after disease onset and decreased
      over time, they may be prognostic for acute phase, but not for chronic phase
      disease. CONCLUSIONS: Renal biopsy timing may alter the significance of variables
      used in the Oxford classification.

PMID- 24912605
TI  - Failure to replicate the structure of a Spanish-language brief Wisconsin
      Inventory of Smoking Dependence Motives across three samples of Latino smokers.
AB  - BACKGROUND: Research in smoking is hindered by a lack of validated measures
      available in languages other than English. Availability of measures in languages
      other than English is vital to the inclusion of diverse groups in smoking
      research. To help address this gap, this study attempted to validate a Spanish
      language version of the brief Wisconsin Inventory of Smoking Dependence Motives
      (Brief WISDM). METHODS: Data from 3 independent, diverse samples of Spanish
      speaking Latino smokers seeking cessation counseling were utilized. Confirmatory
      factor analyses of 3 known structures of the Brief WISDM were examined for fit
      within each sample. A separate analysis was also conducted with the 3 samples
      combined. A post-hoc exploratory factor analyses with the combined sample was
      also conducted. RESULTS: Across 12 confirmatory factor analyses, none of the 3
      structures demonstrated good fit in any of the samples independently or in the
      combined sample. Across the 3 samples, high intercorrelations (>.90) were found
      among the Loss of Control, Craving, Tolerance, and Cue Exposure scales,
      suggesting great redundancy among these scales. An exploratory factor analyses
      (EFAs) further supported these high intercorrelations. Some subscales remained
      intact in the EFA but accounted for little variance. CONCLUSIONS: Overall, this
      study was unable to replicate the structure of a Spanish-language Brief WISDM in
      3 independent samples of smokers. Possible explanations include inadequate
      translation of the measure and/or true and meaningful differences in the
      construct of dependence among Spanish-speaking Latino smokers. Both possibilities
      merit further research.

PMID- 24912607
TI  - Disaster behavioral health: legal and ethical considerations in a rapidly
      changing field.
AB  - Disaster behavioral health is increasingly regarded as a central part of disaster
      preparedness, response and recovery. Legal and ethical issues have received
      relatively little attention and have sparked divergent opinions. Optimally,
      understanding and applying legal and ethical considerations requires an
      understanding of the evolution of the disaster behavioral health field and the
      context of disaster response and recovery. In addition, there are many legal and
      ethical questions identified for consideration, and many ways to approach
      reaching understanding and consensus. Traditionally, discussions of disaster
      behavioral health, including legal and ethical issues, have not included
      understanding decision making processes that occur in extreme circumstances.
      Models which interpret disaster response operations as complex adaptive systems
      are presented for consideration as useful tools for preparing mental health
      workers for effectively delivering services in acute disaster response
      environments.

PMID- 24912608
TI  - Late cardiac metastasis from colorectal carcinoma 15 years after surgery.
AB  - Late recurrence of malignant tumors in the heart more than 10 years after surgery
      is quite rare, especially for colorectal carcinoma. Here, we report a case of
      late cardiac metastasis from a primary colorectal carcinoma, which occurred more
      than 15 years after the initial surgery. To our knowledge, this is the first such
      reported case. 

PMID- 24912606
TI  - Natural products and supplements for geriatric depression and cognitive
      disorders: an evaluation of the research.
AB  - Numerous geriatric patients are using Complementary and Alternative Medicine
      (CAM) for late-life mood and cognitive disorders. Natural products and
      supplements are a common CAM intervention which have risks and benefits of which
      patients should be appropriately advised. The data for omega-3 fatty acids,
      ginkgo biloba, SAMe, St John's wort, B vitamins and vitamin D, huperzine,
      caprylidene, and coconut oil will be evaluated. Since the evidence basis for
      natural products and supplements is limited, especially for the geriatric
      population, studies involving the general adult population are included to infer
      effects in the aging population. Despite the data available, more rigorous
      studies with larger sample sizes over longer periods of time are still needed.
      Regardless of a physician's preference to recommend various natural supplements
      and products, a physician could protect their patients by having an understanding
      of the side effects and indications for various natural products.

PMID- 24912609
TI  - Computed tomographic versus catheterization angiography in tetralogy of Fallot.
AB  - AIM: To compare multidetector computed tomographic angiography with the gold
      standard cardiac catheterization and angiography in tetralogy of Fallot. METHODS:
      In 40 consecutive patients over 5 years of age with tetralogy of Fallot,
      multidetector computed tomographic angiography and catheterization angiography
      studies were compared for intracardiac anatomy, pulmonary anatomy and indices,
      coronaries and collaterals. Safety parameters, relative advantages and
      limitations were also analyzed. RESULTS: All catheterization studies required
      hospitalization whereas all tomographic studies were performed as outpatient
      procedures. The need for sedation and amount of contrast used were significantly
      greater in catheterization than in tomographic studies. Complications noted
      during catheterization were access site complications in 4 patients, cyanotic
      spells in 2, transient complete heart block requiring temporary pacing in 2, and
      air embolism in one. No complication was observed during tomographic studies. All
      tomographic studies were adequate, but 2 catheterization studies were inadequate.
      Ventricular septal defects, aortic override, level of right ventricular outflow
      tract obstruction, and pulmonary artery anatomy were equally assessed by both
      imaging modalities. However, tomographic studies missed additional small muscular
      ventricular septal defects. There was a linear correlation between tomographic
      and catheterization studies for pulmonary annulus size, artery sizes, Z-score,
      and Nakata index. There was complete concordance with respect to side of aortic
      arch and detection of collaterals. Coronary anatomy was better delineated in
      tomographic studies. CONCLUSIONS: For preoperative evaluation of tetralogy of
      Fallot patients, multidetector computed tomographic angiography can be used as a
      reliable noninvasive alternative to cardiac catheterization angiography.

PMID- 24912610
TI  - A single evolutionary innovation drives the deep evolution of symbiotic N2
      fixation in angiosperms.
AB  - Symbiotic associations occur in every habitat on earth, but we know very little
      about their evolutionary histories. Current models of trait evolution cannot
      adequately reconstruct the deep history of symbiotic innovation, because they
      assume homogenous evolutionary processes across millions of years. Here we use a
      recently developed, heterogeneous and quantitative phylogenetic framework to
      study the origin of the symbiosis between angiosperms and nitrogen-fixing (N2)
      bacterial symbionts housed in nodules. We compile the largest database of global
      nodulating plant species and reconstruct the symbiosis' evolution. We identify a
      single, cryptic evolutionary innovation driving symbiotic N2-fixation evolution,
      followed by multiple gains and losses of the symbiosis, and the subsequent
      emergence of 'stable fixers' (clades extremely unlikely to lose the symbiosis).
      Originating over 100 MYA, this innovation suggests deep homology in symbiotic N2
      fixation. Identifying cryptic innovations on the tree of life is key to
      understanding the evolution of complex traits, including symbiotic partnerships. 

PMID- 24912611
TI  - Role of preoperative magnetic resonance imaging in the surgical management of
      early-stage breast cancer.
AB  - PURPOSE: To examine the role of preoperative magnetic resonance imaging (pMRI) on
      time to surgery and rates of reoperation and contralateral prophylactic
      mastectomy (CPM) using a population-based study of New Jersey breast cancer
      patients. METHODS: The study included 289 African-American and 320 white women
      who participated in the Breast Cancer Treatment Disparity Study and underwent
      breast surgery for newly diagnosed early-stage breast cancer between 2005 and
      2010. Patients were identified through rapid case ascertainment by the New Jersey
      State Cancer Registry. Association between pMRI and time to surgery was examined
      by using linear regression and, with reoperation and CPM, by using binomial
      regression. RESULTS: Half (49.9 %) of the study population received pMRI, with
      higher use for whites compared with African-Americans (62.5 vs. 37.5 %). After
      adjusting for potential confounders, patients with pMRI versus those without
      experienced significantly longer time to initial surgery [geometric mean = 38.7
      days; 95 % confidence interval (CI) 34.8-43.0; vs. 26.5 days; 95 % CI 24.3-29.0],
      a significantly higher rate of CPM [relative risk (RR) = 1.82; 95 % CI 1.06
      3.12], and a nonsignificantly lower rate of reoperation (RR = 0.76; 95 % CI 0.54
      1.08). CONCLUSIONS: Preoperative MRI was associated with significantly increased
      time to surgery and a higher rate of CPM, but it did not affect the rate of
      reoperation. Physicians and patients should consider these findings when making
      surgical decisions on the basis of pMRI findings.

PMID- 24912612
TI  - The diagnostic value of one-step nucleic acid amplification (OSNA) for sentinel
      lymph nodes in colon cancer patients.
AB  - BACKGROUND: Lymph node status in colon cancer is critical for prognosis
      estimation and treatment allocation. The purpose of this study was to compare the
      performance of one-step nucleic acid amplification (OSNA) through detection of
      cytokeratin 19 mRNA levels with routine pathological examination (RP) and
      multilevel fine pathological examination (FP) in sentinel lymph nodes (SLN),
      detected using the ex vivo SLN mapping (SLNM) procedure, in presurgically defined
      nonmetastatic colon cancer patients. METHODS: In this prospective study, 325 SLNs
      of 128 patients from the Jeroen Bosch Hospital in 's-Hertogenbosch and the Leiden
      University Medical Center were investigated by RP (H&E), FP (H&E and Keratin Pan
      immunohistochemical staining), and OSNA. The SLNs were harvested by the SLNM
      procedure, using Patent blue or Indocyanine green. SLNs were divided and separate
      parts were used for RP, FP, and the OSNA assay. RESULTS: The diagnostic value of
      OSNA was 82.1 and 100 % for both FP and combined method (OSNA and FP) compared
      with RP. An upstaging rate of 20.2 % was obtained with the use of OSNA only and
      36.4 % with the use of FP only. An upstaging rate of 46.5 % was obtained by
      combining the two methods together. CONCLUSIONS: OSNA and FP appeared to be
      promising tools for the detection of lymph node micro- and macrometastases in
      SLNs after SLNM. The performances of OSNA and FP in this study were superior to
      RP. Because OSNA allows analysis of the whole lymph node, sampling bias can be
      avoided. OSNA therefore may improve tumor staging.

PMID- 24912613
TI  - Primary melanoma location on the scalp is an important risk factor for brain
      metastasis: a study of 1,687 patients with cutaneous head and neck melanomas.
AB  - BACKGROUND: Primary cutaneous head and neck melanomas (HNM) are reported to be
      associated with a higher incidence of brain metastasis than trunk and limb
      melanomas (TLM). In this study, the incidence of brain metastases in patients
      with HNM and risk factors for the development of brain metastases were analyzed.
      METHODS: From a large, prospectively-collected database, 1,687 HNM patients and
      8,793 TLM patients who presented with American Joint Committee on Cancer (AJCC)
      stage I and II disease were identified. Survival was assessed using the Kaplan
      Meier method and multivariate Cox regression analysis. Independent risk factors
      were determined by binary logistic regression analysis. RESULTS: The incidence of
      brain metastases 5 years after diagnosis of HNM was 6.7 % compared with 4.7 % for
      brain metastases from TLM (p = 0.003). Patients with scalp melanomas were most
      likely to develop brain metastases (12.7 %). Independent risk factors for brain
      metastasis in patients with HNM were Breslow thickness, ulceration, and scalp
      location. CONCLUSION: Patients with primary scalp melanomas had a much higher
      incidence of brain metastasis than patients with melanomas on other head and neck
      sites, who in turn had a higher incidence than patients with melanomas on sites
      elsewhere on the body. More intensive monitoring of patients with scalp
      melanomas, who are at particularly high risk of brain metastasis, might lead to
      earlier discovery of metastatic disease in the brain, offering the prospect of
      earlier intervention and better outcomes.

PMID- 24912614
TI  - A multi-institutional validation of the prognostic value of the neutrophil-to
      lymphocyte ratio for upper tract urothelial carcinoma treated with radical
      nephroureterectomy.
AB  - BACKGROUND: To externally validate the prognostic impact of preoperative
      neutrophil-lymphocyte ratio (pre-NLR) in patients with upper tract urothelial
      carcinoma (UTUC) following radical nephroureterectomy (RNU). METHODS: A total of
      665 patients from 12 institutions were included. The median follow-up was 28
      months. Associations between pre-NLR level and outcome were assessed using
      multivariate analysis. A pre-NLR level of >3.0 was defined as elevated. RESULTS:
      Pre-NLR levels were elevated in 184 patients (27.7 %), and pre-NLR elevation was
      significantly associated with worse pathological features such as tumor grade 3,
      advanced pT stage, positive lymphovascular invasion (LVI), and lymph node
      involvement in RNU specimens. The 5-year recurrence-free and cancer-specific
      survival rates were 57.0 % (p < 0.001) and 60.2 % (p < 0.001), respectively, in
      patients with elevated pre-NLR, and 69.2 and 77.3 %, respectively, in their
      counterparts. Multivariate analysis showed that elevated pre-NLR was an
      independent risk factor for predicting subsequent disease recurrence (p = 0.037;
      hazard ratio (HR) 1.38) and cancer-specific mortality (p = 0.036;, HR 1.47),
      although the addition of pre-NLR slightly improved the accuracies of the base
      model for predicting both disease recurrence and cancer-specific mortality to
      79.8 % (p = 0.041) and 83.0 % (p = 0.039), respectively (gain in predictive
      accuracy: 0.2 and 0.1 %, respectively). CONCLUSION: This multi-institutional
      study revealed that elevated pre-NLR was significantly associated with worse
      pathological features such as tumor grade 3, advanced pT stage, positive LVI, and
      lymph node involvement in RNU specimens, and elevated pre-NLR was an independent
      risk factor of disease recurrence and cancer-specific mortality in UTUC patients
      treated with RNU.

PMID- 24912615
TI  - Minimally invasive selective neck dissection: a prospective study of
      endoscopically assisted dissection via a small submandibular approach in cT(1
      2_N(0) oral squamous cell carcinoma.
AB  - BACKGROUND: Selective neck dissection (SND) in clinical N0 (cN0) cases of oral
      squamous cell carcinoma (SCC) has been performed by surgeons using a
      retroauricular or modified facelift approach with robotic or endoscopic
      assistance. However, these procedures provide cosmetic satisfaction at the cost
      of possible maximal invasiveness. In this prospective study, we introduced and
      evaluated the feasibility as well as surgical invasiveness and cosmetic outcome
      of endoscopically-assisted SND via a small submandibular approach. METHODS: Forty
      four patients with cT1-2N0 oral SCC (OSCC) were randomly divided into two groups
      of endoscopically-assisted SND and conventional SND. Perioperative and
      postoperative outcomes of patients were evaluated, including the length of the
      incision, operating time for neck dissection, estimated blood loss during the
      operation, amount and duration of drainage, total hospitalization period, total
      number of lymph nodes retrieved, satisfaction scores based on the cosmetic
      results, perioperative local complications, shoulder syndrome, and follow-up
      information. RESULTS: The mean operation time in the endoscopically-assisted
      group (126.04 +/- 12.67 min) was longer than that in the conventional group
      (75.67 +/- 16.67 min). However, the mean length of the incision was 4.33 +/- 0.76
      cm in the endoscopically-assisted SND group, and the amount and duration of
      drainage, total hospital stay, postoperative shoulder pain score, and cosmetic
      outcomes were superior in the endoscopically-assisted SND group. Additionally,
      the retrieved lymph nodes and complications were comparable. CONCLUSIONS:
      Endoscopically-assisted SND via a small submandibular approach had a longer
      operation time than the conventional approach. However, endoscopically-assisted
      SND was feasible and reliable while providing minimal invasiveness and
      satisfactory appearance.

PMID- 24912616
TI  - Assessing in vitro stem-cell function and tracking engraftment of stem cells in
      ischaemic hearts by using novel iRFP gene labelling.
AB  - Near-infrared fluorescence (NIRF) imaging by using infrared fluorescent protein
      (iRFP) gene labelling is a novel technology with potential value for in vivo
      applications. In this study, we expressed iRFP in mouse cardiac progenitor cells
      (CPC) by lentiviral vector and demonstrated that the iRFP-labelled CPC
      (CPC(iRFP)) can be detected by flow cytometry and fluorescent microscopy. We
      observed a linear correlation in vitro between cell numbers and infrared signal
      intensity by using the multiSpectral imaging system. CPC(iRFP) injected into the
      non-ischaemic mouse hindlimb were also readily detected by whole-animal NIRF
      imaging. We then compared iRFP against green fluorescent protein (GFP) for
      tracking survival of engrafted CPC in mouse ischaemic heart tissue. GFP-labelled
      CPC (CPC(GFP)) or CPC labelled with both iRFP and GFP (CPC(iRFP) (GFP)) were
      injected intramyocardially into mouse hearts after infarction. Three days after
      cell transplantation, a strong NIRF signal was detected in hearts into which
      CPC(iRFP) (GFP), but not CPC(GFP), were transplanted. Furthermore, iRFP
      fluorescence from engrafted CPC(iRFP) (GFP) was detected in tissue sections by
      confocal microscopy. In conclusion, the iRFP-labelling system provides a valuable
      molecular imaging tool to track the fate of transplanted progenitor cells in
      vivo.

PMID- 24912617
TI  - Polymer ferroelectric field-effect memory device with SnO channel layer exhibits
      record hole mobility.
AB  - Here we report for the first time a hybrid p-channel polymer ferroelectric field
      effect transistor memory device with record mobility. The memory device,
      fabricated at 200 degrees C on both plastic polyimide and glass substrates, uses
      ferroelectric polymer P(VDF-TrFE) as the gate dielectric and transparent p-type
      oxide (SnO) as the active channel layer. A record mobility of 3.3 cm(2)V(-1)s(
      1), large memory window (~16 V), low read voltages (~-1 V), and excellent
      retention characteristics up to 5000 sec have been achieved. The mobility
      achieved in our devices is over 10 times higher than previously reported polymer
      ferroelectric field-effect transistor memory with p-type channel. This
      demonstration opens the door for the development of non-volatile memory devices
      based on dual channel for emerging transparent and flexible electronic devices.

PMID- 24912618
TI  - How different do visuo-tactile criteria assess caries lesions activity status on
      occlusal surfaces?
AB  - OBJECTIVES: We tested the association between active caries lesions assessed by
      two different criteria and clinical features of these caries lesions. MATERIALS
      AND METHODS: Three examiners examined forty-nine 3- to 12-year-old children: one
      examiner used the Nyvad criteria, another examiner used the International Caries
      Detection and Assessment System with an additional criteria--Lesion Activity
      Assessment (ICDAS + LAA), and a reference examiner classified lesions regarding
      plaque stagnation, colour, lustre, cavities, depth and texture. Logistic
      regressions were used to test associations. For analyses, we grouped sound sites
      and inactive lesions vs active caries lesions, but also considering only inactive
      vs active lesions. RESULTS: Active lesions scored by both criteria were similarly
      associated with different clinical parameters tested, except when the sound sites
      were excluded from the analysis. In these cases, active lesions according to
      ICDAS + LAA were associated only with cavitation and texture. Texture was
      associated with divergences between criteria when differentiating sound or
      inactive lesions from active ones. Fewer divergences in differentiating active
      from inactive lesions were observed when lesions present lustre. CONCLUSION: Most
      clinical signs associated with active caries lesions were similar, but texture
      and severity tend to have a greater importance when using ICDAS + LAA for
      distinguishing caries activity status. Attention should be given to differences
      due to texture and lustre when using different indices.

PMID- 24912620
TI  - Chemokine receptor 7 enhances cell chemotaxis and migration of metastatic
      squamous cell carcinoma of head and neck through activation of matrix
      metalloproteinase-9.
AB  - The mechanisms leading to squamous cell carcinoma of head and neck (SCCHN)
      metastasis are not fully understood. Although evidence shows that the chemokine
      receptor 7 (CCR7) and its ligand CCL19 may regulate tumor dissemination, their
      role is not clearly defined in SCCHN. Matrix metalloproteinases break consisting
      of tissue barrier to the surrounding tissue invasion and metastasis by destroying
      the balance of matrix degradation of the basement membrane of tumor cells and
      extracellular matrix (ECM). We used chemotaxis and migration assays, western
      blotting, gelatin zymography, actin polymerization assay, immunofluorescence
      staining and immunohistochemical analysis to explore whether MMP-9 can be
      activated by CCL19 (CCR7's ligand) and its role in SCCHN. The experiments were
      performed in the metastatic SCCHN cell line PCI-37B after pre-incubation of the
      cells with CCL19 and SB-3CT (inhibitor of MMP-9). Our results demonstrated that
      CCR7 favors PCI-37B cell chemotaxis and migration, upregulation of MMP-9 protein
      and motivates the activity of MMP-9 protein, induces reorganization of the actin
      cytoskeleton and upregulation of MMP-9 protein. SB-3CT can block all these
      effects. Collectively, our data indicated that CCR7 regulates cell chemotaxis and
      migration via MMP-9 in metastatic SCCHN, and these results provide a basis for
      new strategies in preventing metastases of SCCHN.

PMID- 24912619
TI  - A pharmacoproteomic study confirms the synergistic effect of chondroitin sulfate
      and glucosamine.
AB  - Osteoarthritis (OA) is the most common age-related rheumatic disease.
      Chondrocytes play a primary role in mediating cartilage destruction and
      extracellular matrix (ECM) breakdown, which are main features of the OA joint.
      Quantitative proteomics technologies are demonstrating a very interesting power
      for studying the molecular effects of some drugs currently used to treat OA
      patients, such as chondroitin sulfate (CS) and glucosamine (GlcN). In this work,
      we employed the iTRAQ (isobaric tags for relative and absolute quantitation)
      technique to assess the effect of CS and GlcN, both alone and in combination, in
      modifying cartilage ECM metabolism by the analysis of OA chondrocytes secretome.
      186 different proteins secreted by the treated OA chondrocytes were identified.
      36 of them presented statistically significant differences (p <= 0.05) between
      untreated and treated samples: 32 were increased and 4 decreased. The synergistic
      chondroprotective effect of CS and GlcN, firstly reported by our group at the
      intracellular level, is now demonstrated also at the extracellular level. 

PMID- 24912622
TI  - Organic azides: "energetic reagents" for the intermolecular amination of C-H
      bonds.
AB  - This feature article provides an overview of the application of organic azides
      for the intermolecular amination of sp(3) and sp(2) C-H bonds. The catalytic
      activity of several metal complexes was reviewed underlining both synthetic and
      mechanistic aspects of the C-H amination. The majority of the aminated compounds
      reported in literature have been collected in this paper to provide a compendium
      of published procedures. In addition, the discussion of involved mechanisms has
      been included to assist the reader to envisage the future potential of organic
      azides in the synthesis of aza-derivatives. 

PMID- 24912621
TI  - Tumor cell apoptosis mediated by cytoplasmic ING1 is associated with improved
      survival in oral squamous cell carcinoma patients.
AB  - The ING1 epigenetic regulator and tumor suppressor plays a central role in
      apoptosis. The Ing1 gene is functionally inactivated in many cancer types but is
      rarely mutated. Although most studies have implicated the major ING1 isoform,
      p33ING1b, in nuclear apoptotic signalling, we recently discovered a novel and
      potent apoptosis-inducing effect of p33ING1b translocation to the mitochondria in
      response to DNA damage. In the present study, we examined the impact of
      cytoplasmic/mitochondrial localization of p33ING1b in oral squamous cell
      carcinoma (OSCC) patient samples and explored the therapeutic potential of
      adenovirally-overexpressed p33ING1b in OSCC cell lines in combination with
      ionizing radiation (IR) treatment. In contrast with previous reports, we found
      that p33ING1b protein and mRNA levels are higher in OSCC compared to normal
      epithelial cells. In OSCC patient samples, higher levels of intra-tumoral
      cytoplasmic p33ING1b correlated with increased apoptotic markers and
      significantly better patient survival. This association was strongest in patients
      who received post-operative radiotherapy. IR treatment induced p33ING1b
      translocation to the mitochondria and adenoviral-p33ING1b synergized with IR to
      kill OSCC cells. Our results identify a novel functional relationship between
      cytoplasmic p33ING1b and patient survival and highlight the potential for the use
      of p33ING1b as a therapeutic agent in combination with adjuvant radiotherapy in
      OSCC. 

PMID- 24912623
TI  - Awareness of body weight by mothers and their children: repeated measures in a
      single cohort (EarlyBird 64).
AB  - BACKGROUND: Mothers often do not realize when their child is overweight. We aimed
      to compare mothers' perceptions of children's weight before and during puberty,
      and to explore factors at 7 years predicting recognition of overweight at 16
      years. METHODS: Mothers of 237 children (136 boys) from the EarlyBird study
      estimated their own weight category and that of their child aged 7 years and 16
      years. The children estimated their own weight category at 16 years. Annual
      measures: body mass index standard deviation score (BMIsds), per cent fat,
      physical activity. Pubertal development assessed by age at peak height velocity
      (APHV). MATERNAL MEASURES: BMI, education, socio-economic status. RESULTS: At 7
      years 21% of girls and 16% of boys were overweight or obese, rising to 27% and
      22% respectively at 16 years. The accuracy of the mother's perception of her
      child's weight category improved from 44% at 7 years to 74% at 16 years, but they
      were less able to judge overweight in sons than daughters. The mothers' level of
      concern about overweight was greater for girls than boys, and increased for girls
      (52% mothers of overweight/obese girls were worried at 7 years, 62% at 16 years),
      but remained static in the boys (42% vs. 39%). Over 80% of the youngsters
      realized when they were overweight, but 25% normal-weight girls also classed
      themselves as overweight. Only BMI predicted a mother's ability to correctly
      perceive her child's weight. Neither her awareness, nor concern, about the
      child's weight at 7 years had any impact on the trajectory of the child's BMI
      from 7 years to 16 years. CONCLUSIONS: Parents are central to any successful
      weight reduction programme in their children, but will not engage while they
      remain ignorant of the problem. Crucially, any concern mothers may have about
      their child's excess weight at 7 years appears to have no impact on subsequent
      weight change.

PMID- 24912625
TI  - An experimental and theoretical investigation of the N(4S) + C2(1Sigmag+)
      reaction at low temperature.
AB  - Rate constants for the N((4)S) + C2((1)Sigmag(+)) reaction have been measured in
      a continuous supersonic flow reactor over the range 57 K <=T<= 296 K by the
      relative rate technique employing the N((4)S) + OH(X(2)Pi) -> H((2)S) +
      NO(X(2)Pi) reaction as a reference. Excess concentrations of atomic nitrogen were
      produced by the microwave discharge method and C2 and OH radicals were created by
      the in situ pulsed laser photolysis of precursor molecules C2Br4 and H2O2
      respectively. In parallel, quantum dynamics calculations were performed based on
      an accurate global potential energy surfaces for the three lowest lying quartet
      states of the C2N molecule. The 1(4)A'' potential energy surface is barrierless,
      having two deep potential wells corresponding to the NCC and CNC intermediates.
      Both the experimental and theoretical work show that the rate constant decreases
      to low temperature, although the experimentally measured values fall more rapidly
      than the theoretical ones except at the lowest temperatures. Astrochemical
      simulations indicate that this reaction could be the dominant source of CN in
      dense interstellar clouds. 

PMID- 24912626
TI  - Modifications in ankle dorsiflexor activation by applying a torque perturbation
      during walking in persons post-stroke: a case series.
AB  - BACKGROUND: Results obtained in a previous study (Gait Posture 34:358-363, 2011)
      have shown that, in non-disabled participants, a specific increase in ankle
      dorsiflexor (Tibialis anterior [TA]) activation can be induced by walking with a
      torque perturbation that plantarflexes the ankle during the swing phase. After
      perturbation removal, the increased TA activation persisted temporarily and was
      associated with a more dorsiflexed ankle during swing. The objective of the
      present case-series study was to verify if these results can be reproduced in
      persons post-stroke. METHODS: Six participants who sustained a stroke walked on a
      treadmill before, during and after exposure to a torque perturbation applied at
      the ankle by a robotized ankle-foot orthosis. Spatiotemporal gait parameters,
      ankle and knee kinematics, and the electromyographic activity of TA and Soleus
      were recorded. Mean amplitude of the TA burst located around toe off and peak
      ankle dorsiflexion angle during swing were compared across the 3 walking periods
      for each participant. RESULTS: At the end of the walking period with the
      perturbation, TA mean amplitude was significantly increased in 4 of the 6
      participants. Among these 4 participants, modifications in TA activation
      persisted after perturbation removal in 3 of them, and led to a statistically
      significant increase in peak dorsiflexion during swing. CLINICAL IMPLICATIONS:
      This approach may be helpful to evaluate the residual adaptive capacity in the
      ankle dorsiflexors after a stroke and guide decision-making for the selection of
      optimal rehabilitation interventions. Future work will investigate the clinical
      impact of a multiple-session gait training based on this approach in persons
      presenting a reduced ankle dorsiflexion during the swing phase of walking.

PMID- 24912627
TI  - Meta-analysis of the efficacies of extended and standard pancreatoduodenectomy
      for ductal adenocarcinoma of the head of the pancreas.
AB  - BACKGROUND: The purpose of the present study was to evaluate the efficacy of
      extended pancreatoduodenectomy (EPD) and standard pancreatoduodenectomy (SPD) for
      ductal adenocarcinoma of the head of the pancreas via meta-analysis. METHODS:
      Relevant articles (published between 1995 and 2012) were compiled from online
      data sources. A total of nine studies satisfied the selection criteria, including
      a total of 973 patients (478 in the SPD group and 495 in the EPD group).
      Evaluation parameters included 1-, 3-, and 5-year survival, as well as mortality,
      morbidity, and specific morbidity outcomes. RESULTS: Meta-analysis revealed (1)
      differences in morbidity (Odds ratio [OR] = 1.740; 95 % confidence interval [CI],
      0.840-3.600; P = 0.140), mortality (OR = 0.890; 95 % CI, 0.560-1.400; P = 0.620),
      1-year overall survival (OS) rate (OR = 1.20; 95 % CI, 0.490-2.930; P = 0.69), 3
      year OS rate (OR = 0.770; 95 % CI, 0.460-1.280; P = 0.190), and 5-year OS rate
      (OR = 1.12; 95 % CI, 0.690-1.810; P = 0.560) were not significant between EPD and
      SPD. (2) For bile leak (OR = 2.640; 95 % CI, 1.040-6.700; P = 0.040), pancreatic
      leak (OR = 1.740; 95 % CI, 1.040-2.91; P = 0.030), delayed gastric emptying (OR =
      2.090; 95 % CI, 1.240-3.520; P = 0.006), and lymphatic fistula (OR = 6.120; 95 %
      CI, 1.06-35.320; P = 0.040) differences between EPD and SPD were significant,
      whereas other specific morbidities were not significantly different. CONCLUSIONS:
      Extended pancreatoduodenectomy does not improve 1-, 3-, 5-year OS rates compared
      to SPD and there is a trend toward increased bile leak, pancreatic leak, delayed
      gastric emptying, and lymphatic fistula after EPD.

PMID- 24912628
TI  - Laparoscopic vs. open liver resection for hepatocellular carcinoma of cirrhotic
      liver: a case-control study.
AB  - BACKGROUND: Laparoscopic liver resection is considered a safe and feasible
      alternative to open surgery for malignant liver lesions. However, laparoscopic
      surgery in cirrhotic patients remains challenging. The aim of this retrospective
      case-control study was to compare morbidity, mortality, and long-term patient
      survival between laparoscopic liver resections (LLR) and open liver resections
      (OLR) for hepatocellular carcinoma (HCC) in patients with histologically proven
      cirrhosis. METHODS: A total of 45 patients treated with LLR were matched by cause
      of cirrhosis, Child-Pugh score, type of surgical resection (subsegmentectomy,
      segmentectomy, and bisegmentectomy), tumor number, tumor size, and alpha
      fetoprotein value with 45 patients treated with OLR. Pre-, intra-, and post
      operative variables were compared between groups. RESULTS: Compared with OLR, the
      LLR group displayed a significantly shorter operative time (140 vs. 180 min; p =
      0.02), shorter hospital stay (7 vs. 12 days; p < 0.0001), and lower morbidity
      rate (20 vs. 45 % of patients; p = 0.01). A higher rate of R0 resection was
      observed in the LLR group than in the OLR group (95 vs. 85 %; p = 0.03).
      Postoperative ascites was more frequently observed in the OLR group (18 vs. 2 %;
      p = 0.01). Mortality, patient, and disease-free survival rates were similar
      between groups. The 1-, 5-, and 10-year survival rates were 88, 59, and 12 %,
      respectively, in the LLR group and 63, 44, and 22 % in the OLR group (p = 0.27).
      CONCLUSIONS: Significantly shorter operative times, better resection margins,
      lower postoperative complications, and shorter hospital stay were observed in the
      LLR group compared with the OLR group. LLR and OLR have similar overall and
      disease-free survival rates in cirrhotic HCC patients.

PMID- 24912629
TI  - Study of quantitative changes of cereal allergenic proteins after food
      processing.
AB  - BACKGROUND: Within last few years, the occurrence of food allergens and
      corresponding food allergies has been increasing, therefore research into the
      individual allergens is required. In the present work, the effect of cereal
      processing on the amounts of allergenic proteins is studied by modern proteomic
      based approaches. The most important wheat and barley allergens are low-molecular
      weight (LMW) proteins. Therefore we investigated the relative quantitative
      changes of these proteins after food technological processing, namely wheat
      couscous production and barley malting. RESULTS: A comparative study using mass
      spectrometry in connection with the technique of isobaric tag for relative and
      absolute quantification (iTRAQ) revealed that the amount of wheat allergenic LMW
      proteins decreased significantly during couscous production (approximately to 5
      26% of their initial content in wheat flour). After barley malting, the amounts
      of the majority of LMW proteins decreased as well, although to a lesser extent
      than in the case of wheat/couscous. The level of two allergens even slightly
      increased. CONCLUSION: Suggested proteomic strategy proved as universal and
      sensitive method for fast and reliable identification of various cereal allergens
      and monitoring of their quantitative changes during food processing. Such
      information is important for consumers who suffer from allergies.

PMID- 24912631
TI  - Electronic structure of Eu(Fe0.79Ru0.21)2As2 studied by angle-resolved
      photoemission spectroscopy.
AB  - Eu(Fe(0.79)Ru(0.21))2As2 is suggested to be a nodeless superconductor based on
      the empirical correlation between pnictogen height (hPn) and superconducting gap
      behavior, in contrast to BaFe2(As(0.7)P(0.3))2 and Ba(Fe(0.65)Ru(0.35))2As2. We
      studied the low-lying electronic structure of Eu(Fe(0.79)Ru(0.21))2As2 with angle
      resolved photoemission spectroscopy (ARPES). By photon energy dependence and
      polarization dependence measurements, we resolved the band structure in the three
      dimensional momentum space and determined the orbital character of each band. In
      particular, we found that the dz2 -originated zeta band does not contribute
      spectral weight to the Fermi surface around Z, unlike BaFe2(As(0.7)P(0.3))2 and
      Ba(Fe(0.65)Ru(0.35))2As2. Since BaFe2(As(0.7)P(0.3))2 and
      Ba(Fe(0.65)Ru(0.35))2As2 are nodal superconductors and their hPn's are less than
      1.33 A, while the hPn of Eu(Fe(0.79)Ru(0.21))2As2 is larger than 1.33 A, our
      results provide more evidence for a direct relationship between nodes, dz2
      orbital character and hPn. Our results help to provide an understanding of the
      nodal superconductivity in iron-based superconductors.

PMID- 24912630
TI  - The evolution and development of neural superposition.
AB  - Visual systems have a rich history as model systems for the discovery and
      understanding of basic principles underlying neuronal connectivity. The compound
      eyes of insects consist of up to thousands of small unit eyes that are connected
      by photoreceptor axons to set up a visual map in the brain. The photoreceptor
      axon terminals thereby represent neighboring points seen in the environment in
      neighboring synaptic units in the brain. Neural superposition is a special case
      of such a wiring principle, where photoreceptors from different unit eyes that
      receive the same input converge upon the same synaptic units in the brain. This
      wiring principle is remarkable, because each photoreceptor in a single unit eye
      receives different input and each individual axon, among thousands others in the
      brain, must be sorted together with those few axons that have the same input. Key
      aspects of neural superposition have been described as early as 1907. Since then
      neuroscientists, evolutionary and developmental biologists have been fascinated
      by how such a complicated wiring principle could evolve, how it is genetically
      encoded, and how it is developmentally realized. In this review article, we will
      discuss current ideas about the evolutionary origin and developmental program of
      neural superposition. Our goal is to identify in what way the special case of
      neural superposition can help us answer more general questions about the
      evolution and development of genetically "hard-wired" synaptic connectivity in
      the brain.

PMID- 24912632
TI  - [Relationship between endothelial damage and p120-catenin in paraquat
      intoxication and the protective effect of mangiferin].
AB  - OBJECTIVE: To investigate the relationship between endothelial damage and p120
      catenin (p120-ctn) in a model of paraquat intoxication, and the modulatory effect
      of mangiferin on p120-ctn. METHODS: Human umbilical vein endothelial cells
      (HUVECs) were cultured in two compartment spreading apparatus in vitro. The
      endothelial cells were divided into three groups: control group (cultured in DMEM
      with 10% fetal bovine serum), paraquat group (paraquat was added to the medium
      with final concentration of 0.05 MUmol/L) and mangiferin group (cultured in
      medium with addition of paraquat for 30 minutes, then mangiferin was added in a
      final concentration of 20 MUmol/L). The cellular permeability at 6, 12, 24, 48,
      72 hours after culture in the three groups was measured. The expressions of p120
      ctn 1A, p120-ctn 3A mRNA and p120-ctn protein were measured by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western Blot analysis. The
      distribution of p120-ctn protein was observed by immunofluorescence. RESULTS:
      Compared with control group, cellular permeability in paraquat and mangiferin
      groups were increased with prolongation of time, and peaked at 72 hours [(29.86
      +/- 3.98)%, (24.39 +/- 2.79)% vs. (11.71 +/- 1.67)%, both P<0.05]. The cellular
      permeability was significantly lower in mangiferin group than that in paraquat
      group at different time points (all P<0.05). At 6 hours after intoxication, the
      expressions of p120-ctn 1A, p120-ctn 3A mRNA (gray value) and p120-ctn protein
      (gray value) were significantly lower in paraquat group than those in control
      group (p120-ctn 1A mRNA: 0.150 +/- 0.024 vs. 0.433 +/- 0.024, p120-ctn 3A mRNA:
      0.316 +/- 0.043 vs. 0.701 +/- 0.020, p120-ctn protein: 0.485 +/- 0.031 vs. 0.763
      +/- 0.038, all P<0.01). The expressions of p120-ctn 1A, p120-ctn 3A mRNA and p120
      ctn protein were significantly higher in mangiferin group than those in paraquat
      group from 6 hours on (p120-ctn 1A mRNA: 0.281 +/- 0.021 vs. 0.150 +/- 0.024,
      p120-ctn 3A mRNA: 0.602 +/- 0.042 vs. 0.316 +/- 0.043, p120-ctn protein: 0.675 +/
      0.031 vs. 0.485 +/- 0.031, all P<0.01), and they were gradually increased with
      prolongation of time, and peaked at 72 hours (p120-ctn 1A mRNA: 1.376 +/- 0.128
      vs. 0.150 +/- 0.024, p120-ctn 3A mRNA: 1.251 +/- 0.059 vs. 0.316 +/- 0.043, p120
      ctn protein: 0.844 +/- 0.050 vs. 0.485+/-0.031, all P<0.01). Under upright
      fluorescence microscope, p120-ctn was mainly distributed in the cell membrane in
      control group, with a slight expression in cytoplasm, and no expression in the
      nuclei. With prolongation of time, p120-ctn expression in the cell membrane was
      gradually decreased in paraquat group, while it was increased in the cytoplasm
      and nuclei, with blurring of cell membrane and widening of cellular gap. p120-ctn
      expression was improved on the cell membrane in mangiferin group at corresponding
      time points, with decreased in expression in nuclei and cytoplasm. CONCLUSIONS:
      The p120-ctn protein plays an important role in the enhancement of endothelial
      permeability in paraquat intoxication, and mangiferin may attenuate endothelial
      injury in paraquat intoxication possibly through modulation of p120-ctn protein.

PMID- 24912634
TI  - [An analysis of relevant factors of early death in acute paraquat poisoning].
AB  - OBJECTIVE: To determine the clinical indicators of early death (within 72 hours)
      in patients with acute paraquat poisoning. METHODS: The data of 93 acute paraquat
      poisoning patients admitted to emergency intensive care unit (EICU) of the First
      Hospital of China Medical University were retrospectively analyzed. The patients
      were divided into two groups according to whether they died within 72 hours or
      not. The gender, age, poison dose, paraquat concentration in urine, reduction of
      paraquat amount in urine after each hemoperfusion, and the worst value of white
      blood cell (WBC) count, lymphocytes count, arterial blood gas analysis, blood K+,
      Na+, Cl-, and serum amylase, serum lipase, serum total bilirubin, troponin I,
      creatine kinase (CK), blood urea nitrogen, serum creatinine within 24 hours after
      poisoning were compared. Spearman correlation analysis was used to analyze the
      correlation between paraquat concentration in urine and the dose of paraquat. The
      predictive value of each indicator at death in early stage of poisoning was
      analyzed with receiver operating characteristic curve (ROC curve). RESULTS:
      Nineteen patients in the group of those died in early stage of poisoning (within
      72 hours) resulted in a mortality rate of 20.4%. Compared with non-early death
      group, in early death group, the value of poison dose (133.4 +/- 108.8 mL vs.
      58.6 +/- 40.0 mL, t=3.145, P=0.002), paraquat concentration in urine [16.34
      (11.87, 96.76) mg/L vs. 4.46 (1.21, 12.78) mg/L, Z=-3.422, P=0.001], WBC (22.63
      +/- 9.72 * 109/L vs. 14.95 +/- 8.39 * 109/L, t=3.446, P=0.001), blood lactate
      [Lac: 6.7 (2.2, 12.1) mmol/L vs. 1.9 (1.1, 3.4) mmol/L, Z=-3.294, P=0.001] were
      significantly higher, and the reduction rate of paraquat concentration in urine
      after first perfusion [(38.4 +/- 15.63)% vs. (67.59 +/- 27.87)%, t=2.945,
      P=0.004] and arterial partial pressure of carbon dioxide (PaCO2: 28.7 +/- 9.3
      mmHg vs. 34.8 +/- 6.7 mmHg, t=-3.245, P=0.002) were significantly lowered. There
      was no significant difference between two groups in other indexes. Poison dose
      and paraquat concentration in urine showed significantly positive correlation
      (r=0.450, P<0.001). ROC curve showed that the predictive value of paraquat
      concentration in urine, WBC, and Lac in early death were significant [area under
      the ROC curve (AUC) of paraquat concentrations in urine was 0.806, 95% confidence
      interval (95%CI) 0.699-0.913, the cut-off value was 11.64 mg/L, with sensitivity
      84.6%, specificity 71.4%; AUC of WBC was 0.734, 95%CI 0.569-0.899, the cut-off
      value was 15.94*10(9)/L with sensitivity 69.2%, specificity 76.8%; AUC of Lac was
      0.729, 95%CI 0.568-0.891, the cut-off value was 1.95 mmol/L with sensitivity
      84.6%, specificity 42.9%]. CONCLUSIONS: Paraquat concentrations in urine, WBC,
      Lac, poison dose and PaCO2 were the risk factors of the early death of the acute
      paraquat poisoning. The research suggests that paraquat concentration in urine,
      WBC and Lac are valuable in predicting early death of the patients.

PMID- 24912633
TI  - [Early acute liver injury in paraquat poisoning rats].
AB  - OBJECTIVE: To observe hepatocellular apoptosis and inflammatory cytokines
      expression and their mechanisms after paraquat poisoning in rat. METHODS: Forty
      Wistar rats were divided into control group (n=8) and model group (n=32) by
      random number table. Rats in model group were intraperitoneally injected with 30
      mg/kg 20% paraquat concentrate, while those in control group were injected with
      normal saline. 0.5, 1, 3, 7 days after reproduction of the model, 8 rats were
      sacrificed, and blood was collected from inferior vena cava and hepatic tissue
      was harvested. The serum levels of interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent
      assay (ELISA). The mRNA expressions of IL-1beta, TNF-alpha, inducible nitric
      oxide synthase (iNOS) and p53 were determined by reverse transcription-polymerase
      chain reaction (RT-PCR). Cysteine-containing aspartate-specific proteases
      (caspase-3, -8, -9, -12) activity in hepatic tissue was determined on the 3rd day
      with chromogenic substrate method. The liver histopathological changes were
      observed after hematoxylin-eosin (HE) staining. RESULTS: In model group, hepatic
      tissue showed extensive necrosis with inflammatory cell infiltration in time
      dependant manner. Serum IL-1beta and TNF-alpha levels were significantly higher
      in model group half a day after reproduction than those in control group (IL
      1beta: 220.13 +/- 69.74 ng/L vs. 0.14 +/- 0.03 ng/L, TNF-alpha: 102.66 +/- 26.43
      ng/L vs. 0.16 +/- 0.02 ng/L, P<0.01 and P<0.05), and peaked on the 3rd day and
      1st day (IL-1beta: 423.72 +/- 153.11 ng/L, TNF-alpha: 690.35 +/- 229.64 ng/L).
      They then decreased gradually, but were still significantly higher than those in
      control group on the 7th day (IL-1beta: 357.47 +/- 87.28 ng/L, TNF-alpha: 12.39
      +/- 5.06 ng/L, both P<0.05). The contents of IL-1beta, TNF-alpha and iNOS mRNA
      expressions in hepatic tissue were significantly higher than those in control
      group, and the highest values were seen on the 1st day, the 1st day, and the 3rd
      day [IL-1beta mRNA (gray value): 1.569 +/- 0.057 vs. 0.123 +/- 0.016, TNF-alpha
      mRNA (gray value): 0.683 +/- 0.077 vs. 0.261 +/- 0.025, iNOS mRNA (gray value):
      3.259 +/- 0.135 vs. 0.002+/-0.001, P<0.05 or P<0.01]. There was no difference in
      p53 mRNA expression between model group and control group at early stage, and
      both of them showed low expression, and p53 mRNA expression was significantly
      higher in model group on the 7th day (gray value: 2.959+/-0.086 vs. 0.263+/
      0.032, P<0.01). In model group, caspase activity in liver tissue were
      significantly higher on the 3rd day than those in control group (caspase-3:
      857.25+/-309.26 pmol/mg vs. 169.73+/-48.21 pmol/mg, caspase-8: 199.18+/-61.41
      pmol/mg vs. 32.26+/-11.09 pmol/mg, caspase-9: 321.62+/-80.73 pmol/mg vs. 90.38+/
      29.76 pmol/mg, caspase-12: 413.13+/-89.77 pmol/mg vs. 26.73+/-9.86 pmol/mg, all
      P<0.01). CONCLUSIONS: Paraquat can cause acute liver injury in rats, with caspase
      3, -8, -9, -12 activities markedly enhanced, and liver injury may be associated
      with an early high expression of TNF-alpha, iNOS and p53 gene.

PMID- 24912635
TI  - [Total flavonoids from Astragalus complanatus attenuates lung injury following
      paraquat poisoning in rats through inhibiting excessive endoplasmic reticulum
      stress and c-Jun N-terminal kinase pathway].
AB  - OBJECTIVE: To investigate the effect of total flavonoids from astragalus
      complanatus (FAC) on attenuating lung injury resulted from paraquat (PQ)
      poisoning by inhibiting excessive endoplasmic reticulum stress (ERS) and c-Jun N
      terminal kinase (JNK) pathway in rat. METHODS: Forty-eight Sprague-Dawley (SD)
      rats were randomly divided into six groups (n=8 in each group), including control
      group, model group, dimethyl sulfoxide (DMSO) vehicle control group, and FAC in
      low, medium, and high dosage groups. The model was reproduced by giving PQ 80
      mg/kg orally to induce lung injury. The rats in control group were treated with
      saline by gavage. The rats in DMSO group were given 10% DMSO 20 mL/kg by gavage 2
      hours before intraperitoneal injection of PQ, and those in FAC low, medium and
      high dosage groups received 40, 80, 160 mg*kg(-1)*d(-1) of FAC solution
      intraperitoneally after the PQ administration. The rats were sacrificed 72 hours
      after giving PQ, and the left lung tissue was harvested 72 hours after the
      reproduction of experimental model. The ratio of wet/dry weight (W/D) and total
      lung water content (TLW) were determined. The pathohistological changes of the
      left lung was observed under light microscope, and scored with alveolar damage
      index of quantitative assessment (IQA). The mRNA expressions of JNK and glucose
      regulated protein 78 (GRP78) were determined by reverse transcription-polymerase
      chain reaction (RT-PCR), and the protein expression of JNK, phosphorylation-JNK
      (p-JNK), and GRP78 were determined by Western Blot. RESULTS: Compared with
      control group, the W/D ratio, TLW and IQA were increased significantly in model
      group and DMSO group, and the mRNA expressions of JNK and GRP78 and the protein
      expressions of JNK, p-JNK and GRP78 were markedly increased. Compared with the
      model group, the W/D ratio, TLW and IQA, and the expressions of JNK mRNA and p
      JNK protein were significantly decreased in the FAC groups, especially in FAC
      high dosage group [W/D ratio: 3.0+/-0.3 vs. 5.5+/-0.5, TLW: 2.2+/-0.3 vs. 4.7+/
      0.4, IQA: (15.4+/-3.0)% vs. (40.0+/-5.7)%, JNK mRNA: 0.21+/-0.08 vs. 0.82+/-0.27,
      p-JNK protein: 0.31+/-0.09 vs. 0.78+/-0.25, all P<0.01]. The mRNA expression of
      GRP78 and the protein expressions of JNK and GRP78 were highly expressed in FAC
      low, medium and high dosage groups, and there was no significant difference
      compared with those in model group (GRP78 mRNA: 0.54+/-0.18 vs. 0.74+/-0.20, JNK
      protein: 0.76+/-0.27 vs. 0.80+/-0.28, GRP78 protein: 0.51+/-0.18 vs. 0.69+/-0.21,
      all P>0.05). CONCLUSIONS: PQ induces excessive ERS in the lung tissue resulting
      in lung injury. FAC has a protective effect on lung against PQ injury, and it may
      be related with inhibition JNK pathway in ERS.

PMID- 24912636
TI  - [The interventional effect of Xuebijing injection on expression of mitochondrial
      fusion protein 2 and the ultrastructure changes in lung tissues in rats with
      paraquat poisoning].
AB  - OBJECTIVE: To investigate the mechanism of pulmonary fibrosis induced by paraquat
      (PQ), and the effect of Xuebijing injection in treatment of PQ poisoning.
      METHODS: Seventy-two male Wistar rats were randomly divided into control group,
      PQ poisoning group, and Xuebijing intervention group, with 24 rats in each group.
      Pulmonary fibrosis was induced by single gavage at the dosage of 50 mg/kg of PQ,
      while 1 mL of distilled water was given by gavage in control group. Xuebijing
      injection at the dosage of 4 mL/kg were given intraperitoneally at 30 minutes
      after exposure to PQ in Xuebijing group, and it was repeated every 12 hours; same
      amount of physiological saline was given intraperitoneally in PQ group and
      control group. The experiment lasted for 14 days. Six rats in each group were
      sacrificed on 1, 3, 7, 14 days, respectively, after insult, and 30 minutes after
      the last intervention. The lung tissues were harvested, the changes in pathology
      in lung tissue and the degree of pulmonary fibrosis were observed with optical
      microscope with hematoxylin-eosin (HE) staining and Masson stain. The
      ultrastructure changes in lung tissues were observed with transmission electron
      microscopic, and the content of hydroxyproline (HYP) in the lung tissue was
      determined by alkaline hydrolysis. The expression of mitochondrial fusion protein
      2 (Mfn2) was determined by Western Blot. RESULTS: (1) HE staining: in PQ group,
      inflammation was most marked on the 3rd day. On the 7th day, exudates in the
      alveoli started to be organized, and hypertrophic fibroblasts were seen to
      secrete slim collagen fibers, and fibrosis could be seen in alveoli. On the 14th
      day, intensive hyperplasia of fibroblasts could be observed, and the alveolar
      structure was destroyed and collapsed, with deposition of collagen deposited with
      formation of pulmonary fibrosis. At the same time, pathologic changes were milder
      in Xuebijing group than those in PQ group. (2) Masson staining: the degree of
      inflammation in alveoli and pulmonary fibrosis were less marked in Xuebijing
      group than those of PQ group on the 14th day. (3) Under the transmission electron
      microscopy, it was found that the mitochondria of lung tissue cells was
      relatively less in number on the 14th day in PQ group, and the majority of them
      underwent degeneration, swelling and damage. Basement membrane became folded,
      alveoli were collapsed, and fibrosis was obvious. These changes were less serious
      in Xuebijing group. (4) Content of HYP: contents of HYP in lung tissues on the
      3rd day in PQ group and Xuebijing group were significantly higher than those in
      control group (743.3+/-50.2 MUg/g, 718.1+/-34.0 MUg/g vs. 665.8+/-6.6 MUg/g, both
      P<0.05), it then increased gradually, but the contents of HYP in Xuebijing group
      were significantly lower on the 7th day and 14th day than those in PQ group
      (790.5+/-23.8 MUg/g vs. 876.7+/-42.0 MUg/g, 812.9+/-72.3 MUg/g vs. 931.3+/-33.0
      MUg/g, both P<0.05). (5) Expression of Mfn2: the expression of Mfn2 in control
      group was relatively lower. The expression of Mfn2 in PQ group was increased
      gradually under stress, but its rate was low. The expression of Mfn2 (A value) in
      Xuebijing group was significantly higher than that in PQ group on the 1st day
      (0.731+/-0.035 vs. 0.618+/-0.029, P<0.05), and it was elevated steadily, reaching
      the peak on the 7th day (0.732+/-0.037 vs. 0.669+/-0.034, P<0.05), but it was
      lower than that of PQ group on the 14th day (0.708+/-0.034 vs. 0.765+/-0.041,
      P<0.05). CONCLUSIONS: Xuebijing reduces lung inflammatory reaction and pulmonary
      fibrosis as a result of PQ poisoning. The mechanism is that Xuebijing regulates
      and increases expression of Mfn2 in lung tissue.

PMID- 24912637
TI  - [Reproduction of acute lung injury model induced by paraquat in piglet].
AB  - OBJECTIVE: To reproduce acute lung injury (ALI) model induced by paraquat (PQ) in
      piglet. METHODS: Ten healthy female piglets were divided into control group (n=4)
      and the experimental group (n=6) in accordance with the random number table. The
      experimental group was given intraperitoneal injection of 20% PQ (20 mL) to
      reproduce the model of ALI, while the control group was given the same amount of
      normal saline. All piglets were dynamically monitored with pulse-indicated
      continuous cardiac output (PiCCO) for heart rate (HR), mean arterial pressure
      (MAP), extravascular lung water index (EVLWI) and pulmonary vascular permeability
      index (PVPI). Changes in arterial blood pH, oxygen partial pressure (PaO2),
      partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), peak
      inspiratory pressure (PIP) and platform of the airway pressure (Pplat) were
      recorded until the PaO2/FiO2 <= 300 mmHg. Pathological changes in lung tissue
      under microscopy were observed. RESULTS: Model of ALI induced by PQ was
      successfully reproduced in the experimental group in 5 piglets. The average time
      of successful reproduction was (4.5 +/- 0.2) hours. The HR, MAP, EVLWI, PVPI, PIP
      and Pplat of the experimental group were increased gradually after PQ
      intraperitoneal injection, and all indices were significantly higher than those
      in control group when the model was successfully reproduced (HR: 132.0 +/- 6.9
      bpm vs. 113.0 +/- 3.4 bpm, t=-21.632, P=0.000; MAP: 114.0 +/- 6.0 mmHg vs. 98.0
      +/- 3.5 mmHg, t=-18.217, P=0.000; EVLWI: 19.2 +/- 2.8 mL/kg vs. 12.5 +/- 1.2
      mL/kg, t=-76.283, P=0.000; PVPI: 5.9 +/- 1.3 vs. 3.1 +/- 0.4, t=-31.879, P=0.000;
      PIP: 25.4 +/- 2.5 cmH2O vs. 18.6 +/- 1.5 cmH2O, t=-77.421, P=0.000; Pplat: 19.6
      +/- 2.2 cmH2O vs. 13.5 +/- 1.7 cmH2O, t=-69.452, P=0.000). The pH value, PaO2 and
      PaO2/FiO2 declined gradually while the PaCO2 elevated gradually in experimental
      group after PQ intraperitoneal injection, the differences between the two groups
      were statistically significant (pH value: 7.35 +/- 0.04 vs. 7.43 +/- 0.05,
      t=9.108, P=0.000; PaO2: 82.0 +/- 7.4 mmHg vs. 172.0 +/- 11.6 mmHg, t=102.470,
      P=0.000; PaCO2: 44.0 +/- 4.0 mmHg vs. 35.0 +/- 2.0 mmHg, t=-10.217, P=0.000;
      PaO2/FiO2: 273.0 +/- 14.8 mmHg vs. 573.0 +/- 22.5 mmHg, t=341.565, P=0.000).
      Obvious damage of pulmonary tissue was shown when the model was reproduced.
      CONCLUSIONS: By intraperitoneal injections of 20% PQ 20 mL, a stable PQ-induced
      ALI model can be reproduced in piglets.

PMID- 24912638
TI  - [The efficacy of traditional Chinese medicin in animal model of lung injury
      induced by paraquat: a meta-analysis].
AB  - OBJECTIVE: To systematically review the effect of traditional Chinese medicine
      (TCM) in an animal model of lung injury induced by paraquat (PQ), and to provide
      a theoretical basis for future clinical trials. METHODS: The Wanfang, CNKI, VIP,
      PubMed/MEDLINE, EMBASE database (from January 1979 to September 2012) were
      searched. All papers concerning TCM in animal model of lung injury induced by PQ
      were retrieved. Study selection and data extraction were performed on the basis
      of Cochrane systematic review methods. Weighted mean difference (WMD) and 95%
      confidence interval (95%CI) with random effects model was adopted to investigate
      the effect of TCM on lung injury induced by PQ. RESULTS: Eighteen papers
      involving 1 188 rats met our criteria. Meta-analysis showed that TCM could
      improve the lung coefficiency (WMD -0.07, 95%CI -0.14 to -0.01, P=0.03), reduce
      lung wet/dry weight ratio (WMD -1.15, 95%CI -2.03 to -0.27, P=0.01), increase the
      serum superoxide dismutase (SOD) activity (WMD 56.08, 95%CI 23.46 to 88.70,
      P=0.000 8), improve plasma glutathione peroxidase (GSH-Px) level (WMD 26.64,
      95%CI 18.95 to 34.33, P<0.000 01), and lower serum malondialdehyde(MDA) level
      (WMD -0.65, 95%CI -1.00 to -0.30, P=0.000 2), however there was no significant
      difference in the level of serum tumor necrosis factor-alpha (TNF-alpha) and
      hydroxyproline(HYP) level between TCM and controls (TNF-alpha: WMD -25.15, 95%CI 
      54.87 to 4.57, P=0.10; HYP: WMD -0.11, 95%CI -2.71 to 0.48, P=0.17). CONCLUSIONS:
      These findings demonstrate the efficacy of TCM in animal models of lung injury
      induced by PQ. However taking account of heterogeneity, the efficacy should be
      interpreted with caution.

PMID- 24912639
TI  - [Tumor necrosis factor-alpha induced protein 6 attenuates acute kidney injury
      following paraquat poisoning in rats].
AB  - OBJECTIVE: To explore the effects of tumor necrosis factor-alpha induced protein
      6 (TSG-6) on acute kidney injury (AKI) following paraquat poisoning in rats.
      METHODS: Twenty-four male Sprague-Dawley (SD) rats were randomly divided into
      sham group (n=8), model group (n=8) and TSG-6-treated group (n=8) using a
      randomized number table. Rats were given an injection of 50 mg/kg of paraquat
      intraperitoneally (total volume was equalled to sterile normal saline) in model
      and TSG-6-treated groups. Rats in sham group were given 2 mg/kg of sterile
      saline. After 1 hour of paraquat administration, rats were treated with 30 MUg of
      recombinant human TSG-6 intraperitoneally in TSG-6-treated group. After 6 hours
      of paraquat administration, serum was collected to assess renal function, then
      rats were sacrificed and renal tissues were immediately harvested. AKI score was
      evaluated by renal histopathology and gene expression of pro-inflammatory
      cytokines including interleukins (IL-1beta and IL-6) and tumor necrosis factor
      alpha (TNF-alpha) in kidney was assayed with real-time reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Compared with sham group, blood urea
      nitrogen (BUN), creatinine (Cr) and AKI score were significantly increased in
      model group (BUN: 22.64 +/- 2.36 mmol/L vs. 7.09 +/- 0.65 mmol/L, t=6.986,
      P=0.000; Cr: 177.28 +/- 18.67 MUmol/L vs. 60.32 +/- 3.11 MUmol/L, t=7.134,
      P=0.000; AKI score: 9.14 +/- 0.28 vs. 0.30 +/- 0.23, t=9.013, P=0.000). Moreover,
      the mRNA expressions of IL-1beta, IL-6 and TNF-alpha were significantly elevated
      in model group (IL-1beta mRNA: 3.23+/-0.28 vs. 1.00 +/- 0.07, t=5.874, P=0.000;
      IL-6 mRNA: 4.16 +/- 0.37 vs. 1.00 +/- 0.08, t=7.125, P=0.000; TNF-alpha mRNA:
      3.85 +/- 0.31 vs. 1.00 +/- 0.10, t=6.342, P=0.000). However, serum BUN, Cr, AKI
      score and the mRNA expressions of IL-1beta, IL-6 and TNF-alpha in TSG-6-treated
      group were significantly lower than those in model group (BUN: 14.07 +/- 5.23
      mmol/L vs. 22.64 +/- 2.36 mmol/L, t=2.533, P=0.026; Cr: 112.76 +/- 14.81 MUmol/L
      vs. 177.28 +/- 18.67 MUmol/L, t=2.778, P=0.016; AKI score: 5.35 +/- 0.19 vs. 9.14
      +/- 0.28, t=2.885, P=0.013; IL-1beta mRNA: 2.26 +/- 0.19 vs. 3.23 +/- 0.28,
      t=2.457, P=0.023; IL-6 mRNA: 2.92+/-0.29 vs. 4.16 +/- 0.37, t=2.975, P=0.011; TNF
      alpha mRNA: 2.58 +/- 0.23 vs. 3.85 +/- 0.31, t=2.564, P=0.019). CONCLUSIONS: TSG
      6 attenuates AKI following paraquat poisoning by suppressing inflammatory
      response.

PMID- 24912640
TI  - [Hypoxia/reoxygenation and lipopolysaccharide induced nuclear factor-KappaB and
      hypoxia-inducible factor-1alpha signaling pathways in intestinal epithelial cell
      injury and the interventional effect of emodin].
AB  - OBJECTIVE: To observe pathological process of intestinal epithelial cells
      subjected to ischemia, ischemia/reperfusion injury and inflammation simulated
      hypoxia/reoxygenation (H/R) and lipopolysaccharide (LPS) challenged human fetal
      normal colonic cell (FHC) line in vivo, and to observe the changes when the
      assaulted intestinal epithelial cells were treated with emodin, in order to
      explore the possible intervention targets of emodin. METHODS: Normoxia group: the
      FHC cells were cultured in 95% air and 5% CO2 at 37 centigrade. Hypoxia (H)
      group: the cells were cultured with a mixed anaerobic gas of 1% O2, 5% CO2 and
      94% N2 at 37 centigrade for 1, 2, 3, 4 hours. H + LPS group: the cells were
      cultured in hypoxic condition as H group with simultaneous challenge of LPS (1
      mg/L). H/R group: the cells were cultured in hypoxia for 3 hours followed by
      reoxygenation for 1, 2, 3 and 4 hours, respectively. H/R + LPS group: the cells
      were cultured in H/R as H/R group and LPS (1 mg/L) simultaneously. Emodin
      intervention group: the cells were cultured in H3 h/R2 h + LPS and emodin (20,
      40, 60, 80 MUmol/L) simultaneously. The variation trends of phosphorylation
      nuclear factor-KappaB profilin-alpha (pIKappaB-alpha), phosphorylation NF
      KappaBp65 (pNF-KappaBp65) and their downstream target gene cyclooxygenase-2 (COX
      2), and hypoxia-inducible factor-1alpha (HIF-1alpha) were determined by Western
      Blot. The morphological changes in intestinal epithelium in different groups were
      observed using light microscope. The effect of emodin on the proliferation of
      intestinal epithelial cell was measured by methyl thiazolyl tetrazolium (MTT)
      assay. RESULTS: (1) H group: the expressions of pIKappaB-alpha, pNF-KappaBp65 and
      COX-2 were upregulated, peaking at H1 h (0.350 +/- 0.018, 1.083 +/- 0.054, 0.903
      +/- 0.045), and then they gradually lowered (F value was 3.011, 7.247, 5.754, P
      value was 0.013, 0.000, 0.005, respectively). The expression of HIF-1alpha peaked
      at H3 h (1.511+/-0.076), but there was no significant difference among different
      groups (F=1.881, P=0.062). H + LPS group: the expressions of pIKappaB-alpha, pNF
      KappaBp65, COX-2, HIF-1alpha were increased with elongation of duration of
      hypoxia, and a maximal induction was observed at H3 h (0.504 +/- 0.025, 1.255 +/-
      0.063, 0.812 +/- 0.041, 1.209 +/- 0.075, F value was 2.683, 8.774, 9.765, 2.432,
      and P value was 0.011, 0.000, 0.000, 0.026, respectively). H/R group: with the
      prolonged duration of reoxygenation, the expressions of NF-KappaB signaling
      pathway proteins (pIKappaB-alpha, pNF-KappaBp65, COX-2) were decreased and
      dropped to nadir at H3 h/R4 h (0.712+/-0.034, 1.202+/-0.048, 0.691+/-0.042, F
      value was 1.923, 6.765, 2.719, and P value was 0.063, 0.000, 0.016,
      respectively). Compared with H group, HIF-1alpha was decreased with a prolonged
      duration of reoxygenation in H/R group, but there was no significant difference
      in value among different time points (F=1.280, P=0.081). H/R + LPS group:
      pIKappaB-alpha, pNF-KappaBp65, COX-2, HIF-1alpha showed no sign of degradation
      with the prolonged duration of reoxygenation, and their expression increased to
      maximum analogously at R2-3 h (3.302+/-0.061, 2.315+/-0.055, 2.017+/-0.043,
      2.413+/-0.098, F value was 4.614, 1.652, 5.970, 2.076, and P value was 0.001,
      0.067, 0.000, 0.037, respectively). Emodin group: emodin when co-treated with H/R
      + LPS inhibited the expression of HIF-1alpha and NF-KappaB pathways with a dose
      effect relationship (P<0.05 or P<0.01). Emodin at the dose of 80 MUmol/L showed
      most marked inhibition (2.599+/-0.130, 1.772+/-0.089, 2.590+/-0.129, 2.518+/
      0.125). However, after treatment of emodin did not show such effect. (2) After
      treatment with H/R + LPS, there were morphological changes in cells: vacuoles,
      deformation and fusion. The speed of cell growth became much slower compared with
      H group. (3) Emodin (20-80 MUmol/L) had no significant effect on cell
      proliferation. Although emodin produced biological effect in this concentration
      range, it had no cellular toxicity. CONCLUSIONS: Both hypoxia and inflammation
      can activate the hypoxia pathway of HIF-1alpha and the pro-inflammatory pathway
      of NF-KappaB, but different stimuli cause varying degrees of activation in these
      two pathways. In H/R group, both pathways were weakened during reoxygenation.
      However, in H/R + LPS group, the proteins remained to show a relatively high
      expression during the process of reoxygenation. This may be related to the
      pathophysiological mechanism of intestinal ischemia/reperfusion injury:
      hypoxia/reperfusion injury and LPS act together to destroy the intestinal
      epithelial cells and induce gut-derived sepsis. Emodin may inhibit inflammation
      by blocking HIF-1alpha/NF-KappaB-COX-2 signaling pathways.

PMID- 24912641
TI  - [The role of Nrf2 in the hydrogen treatment for intestinal injury caused by
      severe sepsis].
AB  - OBJECTIVE: To investigate the role of Nrf2 on hydrogen treatment for intestinal
      injury caused by severe sepsis. METHODS: 152 male ICR mice were randomly divided
      into four groups: sham operation group, hydrogen control group, sepsis group, and
      hydrogen treatment group, each n=38. Sepsis model was reproduced by cecal
      ligation and puncture (CLP). The mice in sham operation group and hydrogen
      control group did not receive CLP, and the operative procedure was the same as
      follows. The mice in hydrogen control group and hydrogen treatment group received
      1-hour inhalation of 2% hydrogen 1 hour and 6 hours after sham operation or CLP.
      Twenty animals in each group were selected and observed for 7-day survival
      rate.Eighteen animals in each group were selected and sacrificed at 6, 12 and 24
      hours after CLP. The intestinal tissues were obtained to determine the expression
      of Nrf2 and high mobility group B1 (HMGB1) protein by Western Blot, and the
      expression of Nrf2 mRNA by reverse transcription-polymerase chain reaction (RT
      PCR). The middle portion of jejunum was obtained to evaluate the degree of septic
      injury by light microscope after hematoxylin and eosin (HE) staining. RESULTS:
      There was no statistical significance in variables between sham operation group
      and hydrogen control group. Compared with sham operation group, the 7-day
      survival rate was significantly decreased in sepsis group (0 vs. 100%, P<0.05);
      compared with sepsis group, the 7-day survival rate was significantly increased
      in hydrogen treatment group (55% vs. 0, P<0.05). Compared with sham operation
      group, the expression of Nrf2 protein (gray value) and Nrf2 mRNA were up
      regulated in sepsis group at 6, 12 and 24 hours after CLP (Nrf2 protein 6 hours:
      1.973 +/- 0.350 vs. 1.000 +/- 0.000, t=4.411, P=0.002; 12 hours: 2.367 +/- 0.186
      vs. 1.000 +/- 0.000, t=10.210, P=0.000; 24 hours: 2.517 +/- 0.280 vs. 1.000 +/-
      0.000, t=9.521, P=0.000; Nrf2 mRNA 6 hours: 1.606 +/- 0.271 vs. 1.000 +/- 0.000,
      t=3.631, P=0.002; 12 hours: 1.692 +/- 0.399 vs. 1.000 +/- 0.000, t=3.233,
      P=0.005; 24 hours: 1.784 +/- 0.341 vs. 1.000 +/- 0.000, t=3.894, P=0.001), and it
      was also the expression of HMGB1 (gray value) at 24 hours after CLP operation
      (1.507 +/- 0.220 vs. 1.000 +/- 0.000, t=3.948, P=0.004). Compared with sepsis
      group, the expression of Nrf2 protein and Nrf2 mRNA in intestines were up
      regulated at 6, 12 and 24 hours after CLP in hydrogen treatment group (Nrf2
      protein 6 hours: 2.583 +/- 0.395 vs. 1.973+/-0.350, t=2.765, P=0.024; 12 hours:
      2.725 +/- 0.235 vs. 2.367 +/- 0.186, t=2.674, P=0.028; 24 hours: 2.930 +/- 0.212
      vs. 2.517 +/- 0.280, t=2.595, P=0.032; Nrf2 mRNA 6 hours: 2.008 +/- 0.400 vs.
      1.606+/-0.271, t= 2.405, P=0.029; 12 hours: 2.188 +/- 0.475 vs. 1.692 +/- 0.399,
      t= 2.317, P=0.034; 24 hours: 2.333 +/- 0.406 vs. 1.784 +/- 0.341, t= 2.728,
      P=0.015). Compared with sepsis group, the expression of HMGB1 was down-regulated
      significantly at 24 hours after CLP in hydrogen treatment group (1.147 +/- 0.152
      vs. 1.507 +/- 0.220, t=2.805, P=0.023). HE staining showed that there was
      significantly aggravated intestinal pathological injury in the mice of sepsis
      group; compared with sepsis group, the pathology was significantly less marked in
      hydrogen treatment group. CONCLUSIONS: Through activation of Nrf2-antioxidant
      response element (ARE) pathway, hydrogen may increase the level of Nrf2, which is
      a kind of protective protein, in the intestine of mice, thus decreases the level
      of late pro-inflammatory factor, HMGB1, and it may protect the intestinal tissues
      in septic mice and increase the survival rate significantly.

PMID- 24912642
TI  - [Correlation of intestinal fatty acid binding protein and intestinal injury in
      severe sepsis].
AB  - OBJECTIVE: To investigate the content of intestinal fatty acid binding protein
      (IFABP) and its clinical significance in patients with severe sepsis. METHODS: A
      prospective observational study was conducted. Fifty patients with severe sepsis
      admitted to intensive care unit (ICU) of the First Affiliated Hospital of China
      Medical University from July to December 2012 were enrolled, and 20 healthy
      patients served as control group. The concentrations of serum IFABP, interleukin
      6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were determined with enzyme
      linked immunosorbent assay (ELISA) on days 0, 1 and 3 after ICU admission. Acute
      physiology and chronic health evaluation II (APACHEII) and sequential organ
      failure assessment (SOFA) score, 28-day prognosis, acute gastrointestinal injury
      (AGI) grade were recorded at the same time. Furthermore, the contents of IFABP
      were compared between control group and the severe sepsis group, abdominal
      infection group and non-abdominal infection group, the survival group and the
      death group, as well as among different AGI-grade groups. Correlation analysis of
      IFABP and inflammatory factors, IFABP and two scores, and IFABP and time of stay
      in ICU and mechanical ventilation were studied. Multivariate logistic regression
      and analysis of 28-day outcome of the patients were also studied. RESULTS: IFABP
      levels were increased in severe sepsis patients on days 0, 1 and 3 compared with
      those of healthy control group (731.90+/-53.91 mg/L, 592.07 +/- 41.94 mg/L,
      511.85 +/- 47.97 mg/L vs. 439.88 +/- 23.68 mg/L, all P=0.000). There was no
      statistical significance of IFABP levels between abdominal infection group and
      non-abdominal infection group, the survival group and the death group, or among
      different AGI-grade groups. The correlation analysis showed that IFABP was
      statistically related with IL-6 (r=0.794, P=0.000), TNF-alpha (r=0.878, P=0.010),
      APACHEII score (r=0.428, P=0.000) in patients with severe sepsis. Significant
      correlations were also found between IFABP and IL-6 (r=0.812, P=0.000), TNF-alpha
      (r=0.885, P=0.000) in abdominal infection group, as well as in non-abdominal
      infection group (IL-6: r=0.739, P=0.000; TNF-alpha: r=0.828, P=0.000). As shown
      by multivariate logistic regression analysis, SOFA scores on days 0, 1, 3 were
      the independent risk factors for death [odds ratio (OR) was 1.624 (P=0.004),
      1.411 (P=0.027), 1.740 (P=0.012), respectively], but IFABP level, AGI grade, and
      APACHEII score had no influence on death rate. CONCLUSIONS: IFABP concentrations
      in patients with severe sepsis were significantly increased, and it is correlated
      well to IL-6, TNF-alpha and APACHEII score, but did not related obviously with
      AGI grade and the prognosis of the patients.

PMID- 24912643
TI  - [Erythromycin for improving enteral nutrition tolerance in adult critical
      patients: a systematic review and meta-analysis].
AB  - OBJECTIVE: To systematically review the efficacy and safety of erythromycin on
      enteral nutrition (EN) tolerance in adult critical care patients. METHODS:
      Databases including PubMed, EMbase, the Cochrane Library, CNKI and Wangfang data
      were retrieved up to June, 2013 to collect the randomized controlled trial (RCT)
      concerning erythromycin in improving EN tolerance or increasing the successful
      rate of postpyloric EN tube as compared with other treatments. Two reviewers
      independently screened the literature, extracted the data, and assessed the
      quality of methodology. Then Meta-analysis was performed using RevMan 5.2
      software. RESULTS: A total of 16 RCTs were included. Ten RCTs involving 668
      patients were included for evaluating erythromycin in improving EN tolerance. Six
      RCTs involving 353 patients were included for evaluating erythromycin to increase
      the successful rate of postpyloric EN tube. The result of Meta-analysis showed
      that compared with placebo, erythromycin could significantly improve the
      successful rate of postpyloric EN tube placement [relative risk (RR)=1.82, 95%
      confidence interval (95%CI) 1.40-2.37, P<0.000 01], while there was no
      significant difference between erythromycin and metoclopramide (RR=1.04, 95%CI
      0.79-1.36, P=0.799). In patients who needed early EN, compared with placebo or
      blank control, erythromycin had higher successful gastric feeding rate over 5
      days (RR=1.89, 95%CI 1.19-3.00, P=0.007). In patients who failed EN, compared
      with metoclopramide, erythromycin could significantly increase the successful
      gastric EN rate for 24 hours (RR=1.30, 95%CI 1.02-1.66, P=0.03), 72 hours
      (RR=1.57, 95%CI 1.15-2.14, P=0.005) and 144 hours (RR=2.04, 95%CI 1.23-3.37,
      P=0.006). The median time of EN intolerance was postponed in erythromycin group
      than that in metoclopramide group. Adverse reactions were reported in 5 studies.
      There was no statistic difference except for the higher diarrhea rate in the
      combination treatment group compared with erythromycin group. CONCLUSIONS:
      Postpyloric EN tube placement rate can be improved by erythromycin, which could
      be a choice of substitute for bedside intubation without fluoroscopy or
      endoscopic assistance. Based on the evidence, we recommended that intravenous
      erythromycin in a small dose of approximately 3 mg/kg weight as an option for EN
      intolerance in critical patients.

PMID- 24912645
TI  - [Colorimetric determination of blood paraquat content and its clinical
      application].

PMID- 24912644
TI  - [The effects of preconditioning and postconditioning with isoflurane on focal
      cerebral ischemi/reperfusion injury in rats].
AB  - OBJECTIVE: To investigate the effects of preconditioning and postconditioning
      with isoflurane on pro-inflammatory cytokines and lipid peroxidation in focal
      cerebral ischemic/reperfusion (I/R) injury in rats. METHODS: Thirty-two Sprague
      Dawley (SD) rats were randomly divided into four groups: control group, model
      group, isoflurane preconditioning group and isoflurane postconditioning group,
      with 8 rats in each group. Rats in control group did not receive any challenge.
      In rats of model group right middle cerebral artery occlusion (MCAO) was
      conducted for 90 minutes. Rats in isoflurane preconditioning group received 2%
      isoflurane exposure for 30 minutes 24 hours before MCAO for 90 minutes. Rats in
      isoflurane postconditioning group were given 60-minute 2% isoflurane exposure
      after reperfusion of right MCAO. Twenty-four hours after the procedure, all rats
      were anesthetized with isoflurane, and blood sample taken from the heart was
      centrifuged, and the pro-inflammatory cytokines, including interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha (TNF-alpha), and lipid peroxidation
      products such as malonaldehyde (MDA) and superoxide dismutase (SOD) were
      determined. The mRNA and protein expression levels of matrix metalloproteinase
      (MMP-2, MMP-9), tight junction protein Calaudin-5 and Occludin were determined by
      reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.
      RESULTS: Compared with control group, serum levels of IL-1beta, TNF-alpha and MDA
      were elevated and activity of SOD decreased in rats of model group (IL-1beta:
      76.81+/-11.14 ng/L vs. 52.43 +/- 8.86 ng/L, TNF-alpha: 64.93 +/- 10.81 ng/L vs.
      33.64 +/- 7.94 ng/L, MDA: 8.63 +/- 1.42 MUmol/L vs. 4.14 +/- 0.98 MUmol/L, SOD:
      0.95 +/- 0.21 U/L vs. 2.36 +/- 0.80 U/L, all P<0.05). After isoflurane
      preconditioning and postconditioning, compared with model group, the levels of IL
      1beta, TNF-alpha and MDA were lowered, while activity of SOD was increased (IL
      1beta: 54.37 +/- 9.06 ng/L, 56.82 +/- 8.67 ng/L vs. 76.81 +/- 11.14 ng/L, TNF
      alpha: 43.72 +/- 6.16 ng/L, 39.49 +/- 9.34 ng/L vs. 64.93 +/- 10.81 ng/L, MDA:
      5.65 +/- 0.83 MUmol/L, 5.82 +/- 0.78 MUmol/L vs. 8.63 +/- 1.42 MUmol/L, SOD: 1.64
      +/- 0.47 U/L, 1.71 +/- 0.52 U/L vs. 0.95 +/- 0.21 U/L, all P<0.05). Focal
      cerebral I/R injury could lead to an increased expression of MMP accompanied with
      a decreased expression of tight junction protein. Compared with model group,
      after isoflurane preconditioning and postconditioning, it was found that there
      were decreased mRNA and protein expression of MMP-2 and MMP-9 (MMP-2 mRNA: 1.25
      +/- 0.08, 1.32 +/- 0.12 vs. 2.48 +/- 0.26, MMP-2 protein: 1.56 +/- 0.09, 1.50 +/-
      0.08 vs. 2.12 +/- 0.11; MMP-9 mRNA: 1.26 +/- 0.13, 1.20 +/- 0.12 vs. 2.74 +/-
      0.28, MMP-9 protein: 1.53 +/- 0.04, 1.51 +/- 0.05 vs. 2.23 +/- 0.09, all P<0.05)
      and increased levels of Calaudin-5 and Occludin (Claudin-5 mRNA: 0.40 +/- 0.08,
      0.38 +/- 0.06 vs. 0.28 +/- 0.03, Claudin-5 protein: 0.80 +/- 0.06, 0.81 +/- 0.07
      vs. 0.39 +/- 0.02; Occludin mRNA: 0.54 +/- 0.07, 0.50 +/- 0.08 vs. 0.26 +/- 0.06,
      Occludin protein: 0.64 +/- 0.06, 0.69 +/- 0.05 vs. 0.49 +/- 0.02, all P<0.05).
      CONCLUSIONS: Preconditioning and postconditioning with isoflurane can lower the
      levels of pro-inflammatory cytokines and the degree of lipid peroxidation, and
      lower the hydrolytic activity of MMP to the tight junction protein in cerebral
      tissue, thereby decrease the loss of tight junction protein and alleviate I/R
      injury.

PMID- 24912646
TI  - [Development and application of drug poisoning treatment software].

PMID- 24912647
TI  - [Effect of early repeated hemoperfusion on prognosis of patients with paraquat
      poisoning].

PMID- 24912648
TI  - [Respiratory failure induced by carbosulfan poisoning: a case report].

PMID- 24912649
TI  - [A comment of morphine titration in patients with severe pain in emergency].

PMID- 24912650
TI  - Review article: the epidemiology and prevention of gastric cancer.
AB  - BACKGROUND: Gastric cancer can be divided into cardia and noncardia gastric
      adenocarcinoma (NCGA). Non cardia gastric cancer is a disease that has declined
      in global incidence but has remained as an extremely lethal cancer. AIM: To
      review recent advances in epidemiology and strategies in prevention of non cardia
      gastric cancer. METHODS: A rapid literature search strategy was developed for all
      English language literature published before March 2013. The search was conducted
      using the electronic databases PubMed and EMBASE. The search strategy included
      the keywords 'stomach neoplasms', 'gastric cancer', 'epidemiology', 'risk
      factor', 'early detection of cancer', 'mass screening', 'cancer burden',
      'prevention' and 'cost-effectiveness'. The search strategy was adjusted according
      to different requirements for each database. The specific search was also
      performed in cancer-related websites for country-specific information. The search
      was limited to past 10 years. RESULTS: Gastric cancer is the fifth most common
      cancer but the third leading cause of cancer death. The case fatality rate is
      75%. Screening by radiological or endoscopic methods has limited success in
      prevention of gastric cancer. Helicobacter pylori has been identified as a
      carcinogen, accounting for 60-70% of gastric cancer globally and eradication is a
      potential preventive measure. A meta-analysis in 2009 demonstrated that
      individuals treated with H. pylori eradication therapy can reduce gastric cancer
      risk. The extended Shandong Intervention trial that lasted 14.3 years showed that
      H. pylori eradication therapy significantly reduced gastric cancer incidence by
      39%. Consensus groups from Asia, Europe and Japan have recommended H. pylori
      eradication as primary prevention in high-risk areas. Following eradication
      therapy, endoscopic surveillance of pre-malignant lesions using enhanced imaging
      appears to be another promising preventive strategy. CONCLUSIONS: Gastric cancer
      remains a major diagnostic and therapeutic challenge. There is emerging evidence
      that H. pylori eradication in high gastric cancer regions can lead to a decline
      in the incidence of this highly lethal disease.

PMID- 24912651
TI  - A comparison of physical activity and sedentary behaviour in 9-11 year old
      British Pakistani and White British girls: a mixed methods study.
AB  - BACKGROUND: Previous studies suggest that British children of South Asian origin
      are less active and more sedentary than White British children. However, little
      is known about the behaviours underlying low activity levels, nor the familial
      contexts of active and sedentary behaviours in these groups. Our aim was to test
      hypotheses about differences between British Pakistani and White British girls
      using accelerometry and self-reports of key active and sedentary behaviours, and
      to obtain an understanding of factors affecting these behaviours using parental
      interviews. METHODS: Participants were 145 girls (70 White British and 75 British
      Pakistani) aged 9-11 years and parents of 19 of the girls. Accelerometry data
      were collected over 4 days and girls provided 24-hour physical activity
      interviews on 3 of these days. Multilevel linear regression models and
      generalised linear mixed models tested for ethnic differences in activity,
      sedentary time, and behaviours. Semi-structured interviews were conducted with
      parents. RESULTS: Compared to White British girls, British Pakistani girls
      accumulated 102 (95% CI 59, 145) fewer counts per minute and 14 minutes (95% CI
      8, 20) less time in moderate to vigorous physical activity per day. British
      Pakistani girls spent more time (28 minutes per day, 95% CI 14, 42) sedentary.
      Fewer British Pakistani than White British girls reported participation in
      organised sports and exercise (OR 0.22 95% CI 0.08, 0.64) or in outdoor play (OR
      0.42 95% CI 0.20, 0.91). Fewer British Pakistani girls travelled actively to
      school (OR 0.26 95% CI 0.10, 0.71). There was no significant difference in
      reported screen time (OR 0.88 95% CI 0.45, 1.73). Parental interviews suggested
      that structural constraints (e.g. busy family schedules) and parental concerns
      about safety were important influences on activity levels. CONCLUSIONS: British
      Pakistani girls were less active than White British girls and were less likely to
      participate in key active behaviours. Sedentary time was higher in British
      Pakistani girls but reported screen-time did not differ, suggesting that British
      Pakistani girls engaged more than White British girls in other sedentary
      behaviours. Interviews highlighted some differences between the groups in
      structural constraints on activity, as well as many shared constraints.

PMID- 24912652
TI  - Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from
      the International Study of Asthma and Allergies in Childhood.
AB  - BACKGROUND: Associations of larger families with lower prevalences of hay fever,
      eczema and objective markers of allergic sensitization have been found fairly
      consistently in affluent countries, but little is known about these relationships
      in less affluent countries. METHODS: Questionnaire data for 210,200 children aged
      6-7 years from 31 countries, and 337,226 children aged 13-14 years from 52
      countries, were collected by Phase Three of the International Study of Asthma and
      Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of
      asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older
      and younger siblings, using mixed (multi-level) logistic regression models to
      adjust for individual covariates and at the centre level for region, language and
      national affluence. RESULTS: In both age groups, inverse trends (P < 0.0001) were
      observed for reported 'hay fever ever' and 'eczema ever' with increasing numbers
      of total siblings, and more specifically older siblings. These inverse
      associations were significantly (P < 0.005) stronger in more affluent countries.
      In contrast, symptoms of severe asthma and severe eczema were positively
      associated (P < 0.0001) with total sibship size in both age groups. These
      associations with disease severity were largely independent of position within
      the sibship and national GNI per capita. CONCLUSIONS: These global findings on
      sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at
      least two distinct trends. Inverse associations with older siblings (observations
      which prompted the 'hygiene hypothesis' for allergic disease) are mainly a
      phenomenon of more affluent countries, whereas greater severity of symptoms in
      larger families is globally more widespread.

PMID- 24912653
TI  - Transfusion of fresh-frozen plasma in critically ill patients with a coagulopathy
      before invasive procedures: a randomized clinical trial (CME).
AB  - BACKGROUND: Prophylactic use of fresh-frozen plasma (FFP) is common practice in
      patients with a coagulopathy undergoing an invasive procedure. Evidence that FFP
      prevents bleeding is lacking, while risks of transfusion-related morbidity after
      FFP have been well demonstrated. We aimed to assess whether omitting prophylactic
      FFP transfusion in nonbleeding critically ill patients with a coagulopathy who
      undergo an intervention is noninferior to a prophylactic transfusion of FFP.
      STUDY DESIGN AND METHODS: A multicenter randomized open-label trial with blinded
      endpoint evaluation was performed in critically ill patients with a prolonged
      international normalized ratio (INR; 1.5-3.0). Patients undergoing placement of a
      central venous catheter, percutaneous tracheostomy, chest tube, or abscess
      drainage were eligible. Patients with clinically overt bleeding,
      thrombocytopenia, or therapeutic use of anticoagulants were excluded. Patients
      were randomly assigned to omitting or administering a prophylactic transfusion of
      FFP (12 mL/kg). Outcomes were occurrence of postprocedural bleeding
      complications, INR correction, and occurrence of lung injury. RESULTS: Due to
      slow inclusion, the trial was stopped before the predefined target enrollment was
      reached. Eighty-one patients were randomly assigned, 40 to FFP and 41 to no FFP
      transfusion. Incidence of bleeding did not differ between groups, with a total of
      one major and 13 minor bleedings (p = 0.08 for noninferiority). FFP transfusion
      resulted in a reduction of INR to less than 1.5 in 54% of transfused patients. No
      differences in lung injury scores were observed. CONCLUSION: In critically ill
      patients undergoing an invasive procedure, no difference in bleeding
      complications was found regardless whether FFP was prophylactically administered
      or not.

PMID- 24912654
TI  - An unusual case of epigastric pain.

PMID- 24912656
TI  - Knockdown of BAMBI inhibits beta-catenin and transforming growth factor beta to
      suppress metastasis of gastric cancer cells.
AB  - The upregulation of bone morphogenetic protein and activin membrane-bound
      inhibitor (BAMBI) has been observed in several types of malignant cancer,
      including thyroid, ovarian, liver and colorectal cancer. However, the
      pathological role and the regulatory mechanism of BAMBI in gastric cancer remain
      to be elucidated. The present study revealed that the expression of BAMBI was
      upregulated in gastric cancer tissue, and was correlated with tumor metastasis,
      disease recurrence and low survival rates in patients. Knockdown of BAMBI in
      aggressive gastric cancer cell lines significantly inhibited their malignant
      behavior, including in vitro invasion and cell proliferation. beta-catenin
      expression was downregulated as a result of knocking down of BAMBI, and TGF-beta
      was downregulated in a similar manner. These results demonstrated the association
      between BAMBI expression and gastric cancer progression, and indicate a promising
      direction for developing novel strategies to improve the prognosis and therapy of
      gastric cancer. 

PMID- 24912657
TI  - Guest editorial: acute promyelocytic leukemia: change from "highly fatal to
      highly curable" leukemia.

PMID- 24912655
TI  - CSF-1R signaling in health and disease: a focus on the mammary gland.
AB  - Colony-stimulating factor-1 (CSF-1), also known as macrophage-colony stimulating
      factor (M-CSF), is the primary growth factor regulating survival, proliferation
      and differentiation of macrophages. It is also a potent chemokine for macrophages
      and monocytes. Signaling via the CSF-1 receptor (CSF-1R) is necessary for the
      production of almost all tissue resident macrophage populations and these
      macrophages participate, via trophic mechanisms, in the normal development and
      homeostasis of tissues and organs in which they reside, including the mammary
      gland. The drawback of this close interaction between macrophages and parenchymal
      cells is that dysregulation of macrophage trophic functions assists in the
      development and progression of many cancers, including breast cancer.
      Furthermore, tumour cells secrete CSF-1 to attract more macrophages to the tumour
      microenvironment where CSF-1R signaling frequently drives the behaviour of these
      tumour-associated macrophages (TAMs) to promote tumour progression and
      metastasis. Evidence is mounting that treated tumours secrete more CSF-1 and the
      increased recruitment of TAMs limits treatment efficacy. Thus, therapeutic
      targeting of the CSF-1R to inhibit TAM function is likely to enhance tumour
      response and improve patient outcomes in the treatment of cancer, including
      breast cancer. 

PMID- 24912658
TI  - Natural history and outcome of 200 outpatients with classical trigeminal
      neuralgia treated with carbamazepine or oxcarbazepine in a tertiary centre for
      neuropathic pain.
AB  - BACKGROUND: The guidelines on trigeminal neuralgia management that have been
      agreed and jointly published by the American Academy of Neurology and the
      European Federation of Neurological Societies recommend carbamazepine (CBZ) and
      oxcarbazepine (OXC) as the first-choice medical treatments in patients with
      trigeminal neuralgia (TN). The aim of this retrospective study was to analyze the
      natural history of classical trigeminal neuralgia in a large cohort of patients,
      focusing on drug responsiveness, side effects related to CBZ and OXC, and changes
      in pain characteristics during the course of disease. FINDINGS: We selected the
      last 100 consecutive patients with typical TN who began treatment with CBZ and
      the last 100 with OXC. All had MRI scans and a complete neurophysiological study
      of trigeminal reflexes. Among them, 22 were excluded on the basis of
      neuroradiological or neurophysiological investigations, to avoid the inclusion of
      patients with possible secondary TN. The initial number of responders was 98%
      with CBZ with a median dose of 600 mg (range 200-1200), and of 94% with OXC, with
      a median dose of 1200 mg (range 600-1800). In a mean period of 8.6 months, 27% of
      responders to CBZ incurred in undesired effects to a level that caused
      interruption of treatment or a dosage reduction to an unsatisfactory level. In a
      mean period of 13 months, the same occurred to 18% of responders to OXC. Among
      patients who had a good initial response, only 3 patients with CBZ and 2 with OXC
      developed late resistance. During the course of disease, paroxysms worsened in
      intensity in 3% of patients, and paroxysms duration increased in 2%. We did not
      observe the onset of a clinically manifest sensory deficit at any time in any
      patient. CONCLUSIONS: Unlike common notion, in our large patient sample the
      worsening of pain with time and the development of late resistance only occurred
      in a very small minority of patients. CBZ and OXC were confirmed to be
      efficacious in a large majority of patients, but the side effects caused
      withdrawal from treatment in an important percentage of patients. These results
      suggest the opportunity to develop a better tolerated drug.

PMID- 24912659
TI  - Diverse and bioactive endophytic Aspergilli inhabit Cupressaceae plant family.
AB  - Aspergilli are filamentous, cosmopolitan and ubiquitous fungi which have
      significant impact on human, animal and plant welfare worldwide. Due to their
      extraordinary metabolic diversity, Aspergillus species are used in biotechnology
      for the production of a vast array of biomolecules. However, little is known
      about Aspergillus species that are able to adapt an endophytic lifestyle in
      Cupressaceae plant family and are capable of producing cytotoxic, antifungal and
      antibacterial metabolites. In this work, we report a possible ecological niche
      for pathogenic fungi such as Aspergillus fumigatus and Aspergillus flavus.
      Indeed, our findings indicate that A. fumigatus, A. flavus, Aspergillus niger
      var. niger and A. niger var. awamori adapt an endophytic lifestyle inside the
      Cupressaceous plants including Cupressus arizonica, Cupressus sempervirens var.
      fastigiata, Cupressus semipervirens var. cereiformis, and Thuja orientalis. In
      addition, we found that extracts of endophytic Aspergilli showed significant
      growth inhibition and cytotoxicity against the model fungus Pyricularia oryzae
      and bacteria such as Bacillus sp., Erwinia amylovora and Pseudomonas syringae.
      These endophytic Aspergilli also showed in vitro antifungal effects on the
      cypress fungal phytopathogens including Diplodia seriata, Phaeobotryon cupressi
      and Spencermartinsia viticola. In conclusion, our findings clearly support the
      endophytic association of Aspergilli with Cupressaceae plants and their possible
      role in protection of host plants against biotic stresses. Observed bioactivities
      of such endophytic Aspergilli may represent a significant potential for
      bioindustry and biocontrol applications. 

PMID- 24912660
TI  - Cardiovascular disease relates to intestinal uptake of p-cresol in patients with
      chronic kidney disease.
AB  - BACKGROUND: Serum p-cresyl sulfate (PCS) associates with cardiovascular disease
      in patients with chronic kidney disease. PCS concentrations are determined by
      intestinal uptake of p-cresol, human metabolism to PCS and renal clearance.
      Whether intestinal uptake of p-cresol itself is directly associated with
      cardiovascular disease in patients with renal dysfunction has not been studied to
      date. METHODS: We performed a prospective study in patients with chronic kidney
      disease stage 1 - 5 (NCT00441623). Intestinal uptake of p-cresol, under steady
      state conditions, was estimated from 24 h urinary excretion of PCS. Primary
      endpoint was time to first cardiovascular event, i.e., cardiac death, myocardial
      infarction/ischemia, ventricular arrhythmia, cardiovascular surgery, ischemic
      stroke or symptomatic peripheral arterial disease. Statistical analysis was done
      using Kaplan-Meier estimates and Cox proportional hazard analyses. RESULTS: In a
      cohort of 200 patients, median 24 h urinary excretion of PCS amounted to 457.47
      MUmol (IQR 252.68 - 697.17). After a median follow-up of 52 months, 25 patients
      reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.037).
      Higher urinary excretion of PCS was directly associated with cardiovascular
      events (univariate hazard ratio per 100 MUmol increase: 1.112, P 0.002). In
      multivariate analysis, urinary excretion of PCS remained a predictor of
      cardiovascular events, independent of eGFR (hazard ratio 1.120, P 0.002).
      CONCLUSIONS: In patients with chronic kidney disease, intestinal uptake of p
      cresol associates with cardiovascular disease independent of renal function. The
      intestinal generation and absorption of p-cresol may be therapeutic targets to
      reduce cardiovascular disease risk in patients with renal dysfunction.

PMID- 24912661
TI  - A new marker set that identifies fetal cells in maternal circulation with high
      specificity.
AB  - OBJECTIVE: Fetal cells from the maternal circulation (FCMBs) have the potential
      to replace cells from amniotic fluid or chorionic villi in a diagnosis of common
      chromosomal aneuploidies. Good markers for enrichment and identification are
      lacking. METHOD: Blood samples from 78 normal pregnancies were used for testing
      the marker-set CD105 and CD141 for fetal cell enrichment. Fetal cell candidates
      were subsequently stained by a cocktail of cytokeratin antibodies, and the gender
      of the fetal cells was explored by fluorescence in situ hybridization (FISH) of
      the X and Y chromosomes. RESULTS: Fetal cell candidates could be detected in 91%
      of the samples, and in 85% of the samples, it was possible to obtain X and Y
      chromosomal FISH results for gender determination. The concordance between gender
      determined by FISH on fetal cells in maternal blood and gender found at birth
      reached 100% if three or more fetal cells with FISH signals could be found in a
      sample. CONCLUSION: The marker set identifies fetal cells with specificity high
      enough to make cell-based noninvasive prenatal diagnosis realistic.

PMID- 24912662
TI  - A flexible simulation platform to quantify and manage emergency department
      crowding.
AB  - BACKGROUND: Hospital-based Emergency Departments are struggling to provide timely
      care to a steadily increasing number of unscheduled ED visits. Dwindling
      compensation and rising ED closures dictate that meeting this challenge demands
      greater operational efficiency. METHODS: Using techniques from operations
      research theory, as well as a novel event-driven algorithm for processing
      priority queues, we developed a flexible simulation platform for hospital-based
      EDs. We tuned the parameters of the system to mimic U.S. nationally average and
      average academic hospital-based ED performance metrics and are able to assess a
      variety of patient flow outcomes including patient door-to-event times,
      propensity to leave without being seen, ED occupancy level, and dynamic staffing
      and resource use. RESULTS: The causes of ED crowding are variable and require
      site-specific solutions. For example, in a nationally average ED environment,
      provider availability is a surprising, but persistent bottleneck in patient flow.
      As a result, resources expended in reducing boarding times may not have the
      expected impact on patient throughput. On the other hand, reallocating resources
      into alternate care pathways can dramatically expedite care for lower acuity
      patients without delaying care for higher acuity patients. In an average academic
      ED environment, bed availability is the primary bottleneck in patient flow.
      Consequently, adjustments to provider scheduling have a limited effect on the
      timeliness of care delivery, while shorter boarding times significantly reduce
      crowding. An online version of the simulation platform is available at
      http://spark.rstudio.com/klopiano/EDsimulation/. CONCLUSION: In building this
      robust simulation framework, we have created a novel decision-support tool that
      ED and hospital managers can use to quantify the impact of proposed changes to
      patient flow prior to implementation.

PMID- 24912663
TI  - Resiniferatoxin for treatment of lifelong premature ejaculation: a preliminary
      study.
AB  - OBJECTIVES: To evaluate the efficacy of resiniferatoxin in the treatment of
      patients with lifelong premature ejaculation. METHODS: A total of 41 outpatients
      (mean age 26.14 +/- 4 years) with premature ejaculation completed the present
      study. They were randomly separated into the resiniferatoxin group and the
      placebo group. The resiniferatoxin group included 11 patients with redundant
      prepuce and 10 patients without redundant prepuce, whereas the placebo group
      contained 10 patients with redundant prepuce and 10 patients without. For the
      treatment, the glans were respectively soaked in 30 mL of resiniferatoxin with a
      concentration of 100 nmol/L or 10% alcohol solution for 30 min before sexual
      intercourse. Clinical efficacy was assessed by using the Chinese Index of Sexual
      Function for Premature Ejaculation-5 and the intravaginal ejaculation latency
      time before or 4 weeks after the treatment. The side-effects were also evaluated.
      RESULTS: In the resiniferatoxin group, the effective rate of patients with
      redundant prepuce was 63.6%, and both the intravaginal ejaculation latency time
      and Chinese Index of Sexual Function for Premature Ejaculation-5 significantly
      increased (P < 0.05). However, the effective rate of patients without redundant
      prepuce was 20%, and there were no significant changes of their intravaginal
      ejaculation latency time and Chinese Index of Sexual Function for Premature
      Ejaculation-5 before and after the resiniferatoxin treatment (P > 0.05). The
      total effective rate of patients treated with resiniferatoxin was 42.9%. In the
      placebo group, the effective rate of patients with or without redundant prepuce
      was 20% and 10%, respectively. The total effective rate of patients treated with
      placebo was 15%, and there were no significant changes of their intravaginal
      ejaculation latency time and Chinese Index of Sexual Function for Premature
      Ejaculation-5 before and after the placebo treatment (P > 0.05). The side-effects
      included a slight burning sensation for the glans penis and dysuria. CONCLUSIONS:
      These preliminary results show that resiniferatoxin might be suitable for
      treating patients with lifelong premature ejaculation and particularly those with
      redundant prepuce.

PMID- 24912664
TI  - Who becomes more violent among Korean adolescents? Consequences of victimisation
      in school.
AB  - BACKGROUND: Mainly Western studies suggest that bullying increases risk of
      subsequent offending. Less is known about risk of violence specifically. Very
      little such research is from Asia - none from Korea. AIM: This study aimed to
      answer three research questions: Is being a victim of bullying in Korean schools
      associated with later perpetration of violent behaviour? Does type of bullying
      influence type of offending? Does school climate or parental control mediate this
      relationship? METHOD: Juvenile justice intake officers identified 606 young
      offenders who were asked to complete questionnaires about their school
      experience, school climate and parental supervision. We used multinomial logit
      model with maximum likelihood estimation to evaluate relationships between the
      variables of interest. RESULTS: Over half (310) of these young people had
      committed at least one violent offence. Seventy-six (13%) reported having
      experienced emotional bullying at school and 31 (5%) physical bullying. Violent
      offending was over twice as likely as property offending to be associated with
      emotional bullying history (OR 2.38, CI 1.13-5.01), but three times less likely
      with physical bullying (OR 0.31, CI 0.11-0.87). In addition, parental control
      (but not school climate) increased the likelihood of violent offending or other
      delinquency by 15% (OR 1.14, CI 1.02-1.26; OR 1.16, CI 1.01-1.32, respectively).
      CONCLUSIONS/IMPLICATIONS: Our overarching finding of a relationship between
      childhood experience of bullying and later delinquency is in line with Western
      findings. Where, however, the latter are equivocal on risk of later violence
      perpetration, we found that being emotionally bullied raises the risk of becoming
      violent. Our findings also underscore the importance of having studies from a
      range of cultures. Predictions from Western studies would be that parental
      control would be protective and school climate a potential risk factor for later
      violence, but, in Korea, where parenting styles tend to be highly authoritarian,
      we found differently.

PMID- 24912665
TI  - Cranial radiation for pediatric T-lineage acute lymphoblastic leukemia: a
      systematic review and meta-analysis.
AB  - There are heterogeneous approaches to cranial radiation therapy (CRT) for T
      lineage acute lymphoblastic leukemia (T-ALL). We performed a systematic review of
      studies that specified a radiation strategy and reported survival for pediatric T
      ALL. Our analysis included 62 publications reporting 78 treatment groups (patient
      n = 5844). The average event-free survival (EFS) was higher by 6% per 5 years (P
      < 0.001). Adjusting for year, EFS differed by radiation strategy. Compared to the
      reference group (CRT for all) which had a year-adjusted EFS of 65% (95%
      confidence interval, CI: 61-69%) the adjusted EFS was significantly worse (rate
      difference (RD) = -9%, 95% CI: -15 to -2%) among studies that used a risk
      directed approach to CRT (P = 0.004). The adjusted EFS for the other strategies
      were not significantly different compared to the reference group: CRT for central
      nervous system positive patients only (RD = -3%, 95% CI: -14 to 7%, P = 0.49);
      CRT omitted for all patients (RD = 5%, 95% CI: -4 to 15%, P = 0.33). CRT may not
      be necessary with current chemotherapy for T-ALL. These findings, however, are
      susceptible to bias and caution should be applied in drawing conclusions on the
      comparative effectiveness of alternative CRT strategies.

PMID- 24912666
TI  - Should U.S. women be screened for cervical cancer with pap tests, HPV tests, or
      both?

PMID- 24912667
TI  - Nature-replicated nano-in-micro structures for triboelectric energy harvesting.
AB  - Triboelectric nanogenerators with nature-replicated interface structures are
      presented. Effective contact areas of the triboelectric surfaces are largely
      enhanced because of the densely packed nano-in-micro hierarchical structures in
      nature. The enlarged contact area causes stronger triboelectric charge density,
      which results in output power increment. The interface engineering also allows
      the improved humidity resistance, which is an important parameter for the stable
      energy harvesting. 

PMID- 24912668
TI  - Otolaryngology-specific emergency room as a model for resident training.
AB  - OBJECTIVES/HYPOTHESIS: There is a paucity of data on junior resident training in
      common otolaryngology procedures such as ear debridement, nasal and laryngeal
      endoscopy, epistaxis management, and peritonsillar abscess drainage. These common
      procedures represent a critical aspect of training and are necessary skills in
      general otolaryngology practice. We sought to determine how a dedicated
      otolaryngology emergency room (ER) staffed by junior residents and a supervising
      attending provides exposure to common otolaryngologic procedures. STUDY DESIGN:
      Retrospective review. METHODS: Diagnostic and procedural data for all patients
      examined in the Massachusetts Eye and Ear Infirmary ER between January 2011 and
      September 2013 were evaluated. RESULTS: A total of 12,234 patients were
      evaluated. A total of 5,673 patients (46.4%) underwent a procedure. Each second
      year resident performed over 450 procedures, with the majority seen Monday
      through Friday (75%). The most common procedures in our study included diagnostic
      nasolaryngoscopy (52.0%), ear debridement (34.4%), and epistaxis control (7.0%)
      CONCLUSIONS: An otolaryngology-specific ER provides junior residents with
      significant diagnostic and procedural volume in a concentrated period of time.
      This study demonstrates utility of a unique surgical education model and provides
      insight into new avenues of investigation for otolaryngology training.

PMID- 24912670
TI  - The Millennium Cohort Family Study: a prospective evaluation of the health and
      well-being of military service members and their families.
AB  - The need to understand the impact of war on military families has never been
      greater than during the past decade, with more than three million military
      spouses and children affected by deployments to Operations Iraqi Freedom and
      Enduring Freedom. Understanding the impact of the recent conflicts on families is
      a national priority, however, most studies have examined spouses and children
      individually, rather than concurrently as families. The Department of Defense
      (DoD) has recently initiated the largest study of military families in US
      military history (the Millennium Cohort Family Study), which includes dyads of
      military service members and their spouses (n > 10,000). This study includes US
      military families across the globe with planned follow-up for 21+ years to
      evaluate the impact of military experiences on families, including both during
      and after military service time. This review provides a comprehensive description
      of this landmark study including details on the research objectives, methodology,
      survey instrument, ancillary data sets, and analytic plans. The Millennium Cohort
      Family Study offers a unique opportunity to define the challenges that military
      families experience, and to advance the understanding of protective and
      vulnerability factors for designing training and treatment programs that will
      benefit military families today and into the future.

PMID- 24912669
TI  - Comprehensive characterization of protein 4.1 expression in epithelium of large
      intestine.
AB  - The protein 4.1 family consists of four members, 4.1R, 4.1N, 4.1B and 4.1G, each
      encoded by a distinct gene. All 4.1 mRNAs undergo extensive alternative splicing.
      Functionally, they usually serve as adapters that link actin-based cytoskeleton
      to plasma membrane proteins. It has been reported that 4.1 proteins are expressed
      in most animal cell types and tissues including epithelial cells and epithelial
      tissues. However, the expression of 4.1 proteins in large intestine has not been
      well characterized. In the present study, we performed RT-PCR, western blot and
      immunohistochemistry analysis to characterize the transcripts, the protein
      expression and cellular localization of 4.1 proteins in the epithelia of mouse
      large intestine. We show that multiple transcripts derive from each gene,
      including eight 4.1R isoforms, four 4.1N isoforms, four 4.1B isoforms and six
      4.1G isoforms. However, at the protein level, only one or two major bands were
      detected, implying that not all transcripts are translated and/or the proteins do
      not accumulate at detectable levels. Immunohistochemistry revealed that 4.1R,
      4.1N and 4.1B are all expressed at the lateral membrane as well as cytoplasm of
      epithelial cells, suggesting a potentially redundant role of these proteins. Our
      findings not only provide new insights into the structure of protein 4.1 genes
      but also lay the foundation for future functional studies. 

PMID- 24912671
TI  - Increasing the repeating units of ethylene glycol-based dimethacrylates directed
      toward reduced oxidative stress and co-stimulatory factors expression in human
      monocytic cells.
AB  - The ethylene glycol-based dimethacrylates are commonly used in biomaterials and
      dental restorative materials as a cross-linking agent. In this study, toxic
      effect of triethylene glycol dimethacrylate (TEGDMA) and poly(ethylene glycol)
      dimethacrylates (PEG-DMAs) with various ethylene glycol repeating units was
      investigated in terms of cytotoxicity, oxidative stress, and the expression of co
      stimulatory factors in human leukemia cell line (THP-1 cells) to verify the
      effect of ethylene glycol repeating units. Note that the 1-octanol/water
      partition coefficient of PEG-based dimethacrylates decreased with increasing the
      ethylene glycol repeating units, indicating that the hydrophilicity of PEG-DMAs
      increased with ethylene glycol repeating units. The toxic effect of PEG-DMAs such
      as cytotoxicity, oxidative stress, and the expression of CD86 in treated THP-1
      cells are reduced with increasing the ethylene glycol repeating units in PEG
      DMAs. However, the expression of CD54 in treated THP-1 cells was not influenced
      with the ethylene glycol repeating units and the maximal expression level of CD54
      was observed at the concentration range of 2-4 mM for all samples. Accordingly,
      hydrophilic character of PEG-DMAs with long ethylene glycol chains definitely
      alleviates the some toxic aspect of PEG-based DMAs. This finding would provide
      important insight into the design of new biomaterials and dental materials with
      superior biocompatibility.

PMID- 24912672
TI  - Loss of EphB6 protein expression in human colorectal cancer correlates with poor
      prognosis.
AB  - Erythropoietin-producing hepatocyte (Eph) receptor family constitutes the largest
      family of tyrosine kinase receptors in the human genome. Loss of EphB6, a kinase
      deficient receptor, correlated with a negative outcome in several carcinomas.
      This study aimed to investigate the expression of EphB6 protein and mRNA levels
      in colorectal cancers (CRCs) and possible correlations with clinicopathological
      variables and prognosis. To assess protein expression level, 124 CRCs and 57
      colorectal adenomas samples were examined by immunostaining, the mRNA level of 43
      paired CRC and the adjacent normal tissues were detected by using SYBR Green real
      time PCR method. Decreased expression of EphB6 protein was found in CRC as
      compared with adenoma and normal tissues (chi(2) = 10.146, P = 0.001 and chi(2) =
      45.333, P < 0.001, respectively). Low EphB6 mRNA expression was detected in 83.8%
      of cancers with negative or low EphB6 protein expression. The loss of EphB6
      protein in CRC was positively associated with poorly differentiation (P < 0.001),
      lymph node metastasis (P = 0.006), Dukes stage (P = 0.002) and depth of invasion
      (P = 0.016). The patients with lymph node metastasis had a worse prognosis
      independently of gender, age, tumor site, stage and differentiation (RR = 0.404,
      CI 0.267-0.213, P < 0.001). Low levels of EphB6 protein expression are associated
      with a shorter mean duration of survival in colorectal cancer. Our results
      demonstrated that EphB6 may represent a novel, useful tissue biomarker for the
      prediction of survival rate in CRC.

PMID- 24912673
TI  - Age and gender patterns in associations between lifestyle factors and physical
      performance in older Korean adults.
AB  - PURPOSE: To investigate age and gender patterns in associations between lifestyle
      factors and physical performance in community-dwelling older Korean adults.
      DESIGN AND METHODS: A cross-sectional study was conducted in a population-based
      sample of an urban area. Randomly sampled older Korean adults (n=664; mean age,
      74.6 years) participated. Data on current physical activity level and doing
      exercise, social participation and hobbies, smoking status, drinking status,
      sleep quality, and physical performance were obtained. Binary logistic regression
      analyses were used to identify the age and gender patterns in associations
      between various lifestyle factors and physical performance. RESULTS: In younger
      (age <85 years) men, significant predictors of poor physical performance by
      logistic regression analysis after adjusting for covariates were current physical
      activity time, doing exercise, and engagement in social activities. In younger
      women, current physical activity time and sleep quality were related to poor
      physical performance. In older (age >= 85 years) men, family gatherings were a
      significant factor. In older women, no lifestyle factor assessed showed a
      significant relationship with poor physical performance. CONCLUSION:
      Interventions implemented to modify lifestyle factors need to focus on age and
      gender subgroups in the elderly population. Lifestyle modification should be
      emphasised as a targeted treatment program for Korean adults aged <85 years.

PMID- 24912674
TI  - The E3 ligase CHIP mediates ubiquitination and degradation of mixed-lineage
      kinase 3.
AB  - Mixed-lineage kinase 3 (MLK3) activates mitogen-activated protein kinase (MAPK)
      signaling pathways and has important functions in migration, invasion,
      proliferation, tumorigenesis, and apoptosis. We investigated the role of the E3
      ligase carboxyl terminus of Hsc70-interacting protein (CHIP) in the regulation of
      MLK3 protein levels. We show that CHIP interacts with MLK3 and, together with the
      E2 ubiquitin-conjugating enzyme UbcH5 (UbcH5a, -b, -c, or -d), ubiquitinates MLK3
      in vitro. CHIP or Hsp70 overexpression promoted endogenous MLK3 ubiquitination
      and induced a decline in MLK3 protein levels in cells with Hsp90 inhibition.
      Furthermore, CHIP overexpression caused a proteasome-dependent reduction in
      exogenous MLK3 protein. Geldanamycin (GA), heat shock, and osmotic shock
      treatments also reduced the level of MLK3 protein via a CHIP-dependent mechanism.
      In addition, CHIP depletion in ovarian cancer SKOV3 cells increased cell
      invasion, and the enhancement of invasiveness was abrogated by small interfering
      RNA (siRNA)-mediated knockdown of MLK3. Thus, CHIP modulates MLK3 protein levels
      in response to GA and stress stimuli, and CHIP-dependent regulation of MLK3 is
      required for suppression of SKOV3 ovarian cancer cell invasion. 

PMID- 24912675
TI  - Cross talk between the TM4SF5/focal adhesion kinase and the interleukin-6/STAT3
      pathways promotes immune escape of human liver cancer cells.
AB  - TM4SF5 overexpressed in hepatocellular carcinoma activates focal adhesion kinase
      (FAK) during tumor cell migration. However, it remains unknown how TM4SF5 in
      hepatocellular carcinoma cells compromises with immune actions initiated by
      extracellular cytokines. Normal and cancerous hepatocytes with or without TM4SF5
      expression were analyzed for the effects of cytokine signaling activity on
      TM4SF5/FAK signaling and metastatic potential. We found that interleukin-6 (IL-6)
      was differentially expressed in hepatocytes depending on cancerous malignancy and
      TM4SF5 expression. IL-6 treatment activated FAK and STAT3 and enhanced focal
      adhesion (FA) formation in TM4SF5-null cells, but it decreased TM4SF5-dependent
      FAK activity and FA formation in SNU761-TM4SF5 cells. STAT3 suppression abolished
      the IL-6-mediated effects in normal Chang cells, but it did not recover the
      TM4SF5-dependent FAK activity that was inhibited by IL-6 treatment in cancerous
      SNU761-TM4SF5 cells. In addition, modulation of FAK activity did not change the
      IL-6-mediated STAT3 activity in either the Chang or SNU761 cell system. TM4SF5
      expression in SNU761 cells caused invasive extracellular matrix degradation
      negatively depending on IL-6/IL-6 receptor (IL-6R) signaling. Thus, it is likely
      that hepatic cancer cells adopt TM4SF5-dependent FAK activation and metastatic
      potential by lowering IL-6 expression and avoiding its immunological action
      through the IL-6-STAT3 pathway. 

PMID- 24912676
TI  - Direct interaction between the WD40 repeat protein WDR-23 and SKN-1/Nrf inhibits
      binding to target DNA.
AB  - SKN-1/Nrf transcription factors activate cytoprotective genes in response to
      reactive small molecules and strongly influence stress resistance, longevity, and
      development. The molecular mechanisms of SKN-1/Nrf regulation are poorly defined.
      We previously identified the WD40 repeat protein WDR-23 as a repressor of
      Caenorhabditis elegans SKN-1 that functions with a ubiquitin ligase to presumably
      target the factor for degradation. However, SKN-1 activity and nuclear
      accumulation are not always correlated, suggesting that there could be additional
      regulatory mechanisms. Here, we integrate forward genetics and biochemistry to
      gain insights into how WDR-23 interacts with and regulates SKN-1. We provide
      evidence that WDR-23 preferentially regulates one of three SKN-1 variants through
      a direct interaction that is required for normal stress resistance and
      development. Homology modeling predicts that WDR-23 folds into a beta-propeller,
      and we identify the top of this structure and four motifs at the termini of SKN
      1c as essential for the interaction. Two of these SKN-1 motifs are highly
      conserved in human Nrf1 and Nrf2 and two directly interact with target DNA.
      Lastly, we demonstrate that WDR-23 can block the ability of SKN-1c to interact
      with DNA sequences of target promoters identifying a new mechanism of regulation
      that is independent of the ubiquitin proteasome system, which can become occupied
      with damaged proteins during stress. 

PMID- 24912677
TI  - ALK5-mediated transforming growth factor beta signaling in neural crest cells
      controls craniofacial muscle development via tissue-tissue interactions.
AB  - The development of the craniofacial muscles requires reciprocal interactions with
      surrounding craniofacial tissues that originate from cranial neural crest cells
      (CNCCs). However, the molecular mechanism involved in the tissue-tissue
      interactions between CNCCs and muscle progenitors during craniofacial muscle
      development is largely unknown. In the current study, we address how CNCCs
      regulate the development of the tongue and other craniofacial muscles using Wnt1
      Cre; Alk5(fl/fl) mice, in which loss of Alk5 in CNCCs results in severely
      disrupted muscle formation. We found that Bmp4 is responsible for reduced
      proliferation of the myogenic progenitor cells in Wnt1-Cre; Alk5(fl/fl) mice
      during early myogenesis. In addition, Fgf4 and Fgf6 ligands were reduced in Wnt1
      Cre; Alk5(fl/fl) mice and are critical for differentiation of the myogenic cells.
      Addition of Bmp4 or Fgf ligands rescues the proliferation and differentiation
      defects in the craniofacial muscles of Alk5 mutant mice in vitro. Taken together,
      our results indicate that CNCCs play critical roles in controlling craniofacial
      myogenic proliferation and differentiation through tissue-tissue interactions. 

PMID- 24912678
TI  - RhoB promotes gammaH2AX dephosphorylation and DNA double-strand break repair.
AB  - Unlike other Rho GTPases, RhoB is rapidly induced by DNA damage, and its
      expression level decreases during cancer progression. Because inefficient repair
      of DNA double-strand breaks (DSBs) can lead to cancer, we investigated whether
      camptothecin, an anticancer drug that produces DSBs, induces RhoB expression and
      examined its role in the camptothecin-induced DNA damage response. We show that
      in camptothecin-treated cells, DSBs induce RhoB expression by a mechanism that
      depends notably on Chk2 and its substrate HuR, which binds to RhoB mRNA and
      protects it against degradation. RhoB-deficient cells fail to dephosphorylate
      gammaH2AX following camptothecin removal and show reduced efficiency of DSB
      repair by homologous recombination. These cells also show decreased activity of
      protein phosphatase 2A (PP2A), a phosphatase for gammaH2AX and other DNA damage
      and repair proteins. Thus, we propose that DSBs activate a Chk2-HuR-RhoB pathway
      that promotes PP2A-mediated dephosphorylation of gammaH2AX and DSB repair.
      Finally, we show that RhoB-deficient cells accumulate endogenous gammaH2AX and
      chromosomal abnormalities, suggesting that RhoB loss increases DSB-mediated
      genomic instability and tumor progression. 

PMID- 24912679
TI  - Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC
      1alpha in the regulation of the hypoxic gene program.
AB  - Skeletal muscle tissue shows an extraordinary cellular plasticity, but the
      underlying molecular mechanisms are still poorly understood. Here, we use a
      combination of experimental and computational approaches to unravel the complex
      transcriptional network of muscle cell plasticity centered on the peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), a
      regulatory nexus in endurance training adaptation. By integrating data on genome
      wide binding of PGC-1alpha and gene expression upon PGC-1alpha overexpression
      with comprehensive computational prediction of transcription factor binding sites
      (TFBSs), we uncover a hitherto-underestimated number of transcription factor
      partners involved in mediating PGC-1alpha action. In particular, principal
      component analysis of TFBSs at PGC-1alpha binding regions predicts that, besides
      the well-known role of the estrogen-related receptor alpha (ERRalpha), the
      activator protein 1 complex (AP-1) plays a major role in regulating the PGC
      1alpha-controlled gene program of the hypoxia response. Our findings thus reveal
      the complex transcriptional network of muscle cell plasticity controlled by PGC
      1alpha. 

PMID- 24912680
TI  - Cyclin D1 and C/EBPbeta LAP1 operate in a common pathway to promote mammary
      epithelial cell differentiation.
AB  - Both cyclin D1 and the transcription factor C/EBPbeta are required for mammary
      epithelial cell differentiation; however, the pathway in which they operate is
      uncertain. Previous analyses of the patterns of gene expression in human tumors
      suggested a connection between cyclin D1 overexpression and C/EBPbeta, but
      whether this represents a cancer-specific gain of function for cyclin D1 is
      unknown. C/EBPbeta is an intronless gene encoding three protein isoforms--LAP1,
      LAP2, and LIP. Here, we provide evidence that cyclin D1 engages C/EBPbeta in an
      isoform-specific manner. Cyclin D1 binds to LAP1, an event that activates the
      transcriptional function of LAP1 by relieving its autoinhibited state effected by
      intramolecular interactions. Reexpression of LAP1 but not LAP2 or LIP restores
      the ability of C/EBPbeta-deficient mammary epithelial cells to differentiate and
      does so in a manner dependent on cyclin D1. And cyclin D1-mediated activation of
      LAP1 participates in mammary epithelial cell differentiation. Our findings
      indicate that cyclin D1 and C/EBPbeta LAP1 operate in a common pathway to promote
      mammary epithelial cell differentiation.

PMID- 24912681
TI  - Reactive oxygen species-mediated DJ-1 monomerization modulates intracellular
      trafficking involving karyopherin beta2.
AB  - Mutations in DJ-1 are a cause of recessive, early-onset Parkinson's disease (PD).
      Although oxidative stress and mitochondrial integrity have been implicated in PD,
      it is largely unknown why neurons degenerate. DJ-1 is involved in oxidative
      stress-mediated responses and in mitochondrial maintenance; however, its specific
      function remains vague. Here we show that DJ-1 exhibits neuronal dynamic
      intracellular trafficking, with dimeric/monomeric cycling modulated by the
      oxidative environment. We demonstrate that oxidative stress enhances
      monomerization of wild-type cytosolic DJ-1, leading to nuclear recruitment. The
      pathogenic DJ-1/E163K variant is unable to homodimerize but is retained in the
      cytosol upon wild-type DJ-1 heterodimerization. We found that this wild
      type/pathogenic heterodimer is disrupted by oxidative stress, leading to DJ
      1/E163K mitochondrial translocation. We further demonstrated that endogenously
      expressed wild-type DJ-1 is imported into neuronal nuclei as a monomer and that
      nucleo-cytoplasmic transport is oxidative stress mediated. We identified a novel
      proline-tyrosine nuclear localization signal (PY-NLS) in DJ-1, and we found that
      nuclear monomeric DJ-1 import is mediated by an oxidative stress-dependent
      interaction with karyopherin beta2. Our study provides evidence that oxidative
      stress-mediated intracellular trafficking of DJ-1, mediated by dynamic DJ-1
      dimeric/monomeric cycling, is implicated in PD pathogenesis. 

PMID- 24912682
TI  - Multiple Arkadia/RNF111 structures coordinate its Polycomb body association and
      transcriptional control.
AB  - The RING domain protein Arkadia/RNF111 is a ubiquitin ligase in the transforming
      growth factor beta (TGFbeta) pathway. We previously identified Arkadia as a small
      ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting
      motifs (SIMs) that together form a SUMO-binding domain (SBD). However, precisely
      how SUMO interaction contributes to the function of Arkadia was not resolved.
      Through analytical molecular and cell biology, we found that the SIMs share
      redundant function with Arkadia's M domain, a region distinguishing Arkadia from
      its paralogs ARKL1/ARKL2 and the prototypical SUMO-targeted ubiquitin ligase
      (STUbL) RNF4. The SIMs and M domain together promote both Arkadia's
      colocalization with CBX4/Pc2, a component of Polycomb bodies, and the activation
      of a TGFbeta pathway transcription reporter. Transcriptome profiling through RNA
      sequencing showed that Arkadia can both promote and inhibit gene expression,
      indicating that Arkadia's activity in transcriptional control may depend on the
      epigenetic context, defined by Polycomb repressive complexes and DNA methylation.

PMID- 24912683
TI  - Functional and biochemical characterization of human eukaryotic translation
      initiation factor 3 in living cells.
AB  - The main role of the translation initiation factor 3 (eIF3) is to orchestrate
      formation of 43S-48S preinitiation complexes (PICs). Until now, most of our
      knowledge on eIF3 functional contribution to regulation of gene expression comes
      from yeast studies. Hence, here we developed several novel in vivo assays to
      monitor the integrity of the 13-subunit human eIF3 complex, defects in assembly
      of 43S PICs, efficiency of mRNA recruitment, and postassembly events such as AUG
      recognition. We knocked down expression of the PCI domain-containing eIF3c and
      eIF3a subunits and of eIF3j in human HeLa and HEK293 cells and analyzed the
      functional consequences. Whereas eIF3j downregulation had barely any effect and
      eIF3a knockdown disintegrated the entire eIF3 complex, eIF3c knockdown produced a
      separate assembly of the a, b, g, and i subunits (closely resembling the yeast
      evolutionary conserved eIF3 core), which preserved relatively high 40S binding
      affinity and an ability to promote mRNA recruitment to 40S subunits and displayed
      defects in AUG recognition. Both eIF3c and eIF3a knockdowns also severely reduced
      protein but not mRNA levels of many other eIF3 subunits and indeed shut off
      translation. We propose that eIF3a and eIF3c control abundance and assembly of
      the entire eIF3 and thus represent its crucial scaffolding elements critically
      required for formation of PICs. 

PMID- 24912685
TI  - Abstracts of the Tissue Engineering & Regenerative Medicine International
      Society, European Chapter Meeting, 10-13 june, 2014, Genova, Italy.

PMID- 24912684
TI  - Seroprevalence of hepatitis B and C virus infections among health students and
      health care workers in the Najran region, southwestern Saudi Arabia: the need for
      national guidelines for health students.
AB  - BACKGROUND: The objectives of the study were to study the seroprevalence of
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among health
      college students (HS) and health care workers (HCWs) in the Najran Region of
      south-western Saudi Arabia and to study the students' knowledge of occupational
      exposure to blood-borne viral infections. METHODS: A cross-sectional study of a
      representative sample of 300 HS and 300 HCWs was conducted. RESULTS: An overall
      seroprevalence of HBV of 1.7% and 8.7% was found among HS and HCWs, respectively.
      Two-thirds of HS (66.7%, 200) and 23.3% (70) of HCWs lack anti-HBs and are
      susceptible to HBV infection. An overall seroprevalence of HCV of 0% and 0.3% was
      found among the HS and HCWs, respectively. The present study indicates poor
      knowledge among HS and moderate knowledge among HCWs regarding occupationally
      transmitted blood-borne diseases, safe injection practices, and standard
      precautions to prevent occupationally transmitted blood-borne infections.
      CONCLUSION: It is mandatory to develop a structured program to raise awareness
      among HS, and current health colleges' curricula should be upgraded to address
      these issues early. The HS should be considered new recruits to health services
      in terms of their initial screening for blood-borne infections and vaccination
      against HBV. The development of a novel continuing medical education and pre
      employment awareness program for HCWs is recommended to address the following:
      blood-borne diseases transmitted occupationally, standard precautions to prevent
      occupationally transmitted blood borne infections, and safe injection practices.

PMID- 24912687
TI  - Decline in hepatitis E virus antibody prevalence in southeastern Germany, 1996
      2011.
AB  - In the past decade, an increasing frequency of acute hepatitis E was noted in
      Germany and other European countries. Moreover, a high prevalence (17%) of
      hepatitis E virus (HEV) immunoglobulin G antibodies (anti-HEV) was recently found
      in the adult German population. Although this suggests an emerging pathogen,
      reports from other countries gave hints to a completely new aspect: a possible
      decrease in anti-HEV prevalence during the last decades. To investigate the time
      trends of hepatitis E in southeastern Germany, we performed anti-HEV testing in
      sera taken from adults in 1996 and 2011. Surplus serum specimens stored during
      routine operations of our diagnostic laboratory were used. The sample comprised
      two sets of 1,092 sera taken in 1996 and 2011, each with 182 specimens in six age
      groups from 20-79 years. Testing was performed using an HEV IgG enzyme
      immunoassay (EIA, Axiom Diagnostics), and the recomLine HEV IgG immunoblot
      (Mikrogen). A significant difference in anti-HEV prevalence was observed between
      the two groups: 50.7% of individuals tested positive in the 1996 group as
      compared to 34.3% in 2011 (EIA, P < 0.001). Results by immunoblot analysis were
      20.5% (1996) versus 14.5% (2011), P < 0.001. Differences were found in all age
      groups and were more pronounced for the 20-39-year age group. CONCLUSION: The
      prevalence of anti-HEV has decreased significantly in the past decades in
      southeastern Germany. The phenomenon of HEV being an emerging pathogen is thus
      most probably due to an increasing awareness of the disease.

PMID- 24912688
TI  - Hydrolysis kinetics and radical-scavenging activity of gelatin under simulated
      gastrointestinal digestion.
AB  - The hydrolysis kinetics and radical-scavenging activity of gelatin were
      investigated under simulated gastrointestinal digestion in this study. In the
      gastric phase, the degree of gelatin hydrolysis increased from 0.17% to 1.20%,
      while the DPPH radical-scavenging rate increased from 6.27% to 24.56%. Further
      digestion in the intestinal phase brought the degree of hydrolysis and radical
      scavenging rate to 26.08% and 44.76%, respectively. After digestion, the gelatin
      hydrolysates were separated into two fractions by ultrafiltration. The fraction
      with an average molecular weight of 312.98 Da exhibited the higher yield (78.26%)
      and radical-scavenging activity (IC50=2.09 mg/ml), suggesting the high
      digestibility and bioactivity of gelatin after oral administration. The fraction
      was further purified with multi-step column chromatography and identified to be
      Gly-Pro-Met (303.38 Da) by UPLC-ESI-MS. These results may help us to better
      understand its physiological effects and to use it properly in foods and
      pharmaceuticals.

PMID- 24912689
TI  - Rapid HPLC analysis of amino acids and biogenic amines in wines during
      fermentation and evaluation of matrix effect.
AB  - A rapid HPLC method has been developed for the simultaneous determination of 23
      amino acids, 10 biogenic amines and the ammonium ion in wine. Samples were pre
      column derivatised with diethyl ethoxymethylenemalonate and separated using
      reversed-phase HPLC within 30 min. The matrix effect was evaluated when measuring
      samples taken from different stages of fermentation. Most compounds showed no
      obvious matrix effect, whereas proline, ethanolamine and spermine had remarkably
      different responses to variable concentrations of sugar. High concentrations of
      sugar affected the pH of the derivatisation reaction system; proline,
      ethanolamine and spermine derivatives were sensitive to this effect. Matrix
      matched calibration was used for the quantification of these compounds.
      Validation of the method showed that it was accurate, reproducible and efficient
      for the simultaneous determination of amino acids and biogenic amines in wines
      during fermentation. As a specific application of the method, red wine samples
      taken from different stages of fermentation were analysed.

PMID- 24912690
TI  - Phenolic profile of Douro wines and evaluation of their NO scavenging capacity in
      LPS-stimulated RAW 264.7 macrophages.
AB  - The phenolic profile of two samples of commercial Douro red wines, a table red
      wine (RM) and a Port wine (PR), was analysed by HPLC-DAD after purification by
      solid phase extraction (SPE). Eighteen phenolic compounds belonging to benzoic
      acids, hydroxycinnamic acids and anthocyanins were determined. The presence of
      tannins in both wines and of polymeric anthocyanins in Port wine could be
      inferred by the chromatograms registered at 280 and 500 nm, respectively. The
      wine extracts showed capacity to scavenge sodium nitroprusside-released nitric
      oxide (NO), RM being more effective than PR, which can be partly attributed to
      its higher content in monomeric anthocyanins. Using a model of macrophages (RAW
      264.7 cells) stimulated with bacterial lipopolysaccharide (LPS) the samples
      showed a similar potential, which may indicate the importance of polymeric
      anthocyanins and the higher amount of phenolic acids present in PR to decrease
      cells NO levels.

PMID- 24912691
TI  - Characterisation and potential application of pineapple pomace in an extruded
      product for fibre enhancement.
AB  - This study characterised pineapple pomace (PP) and evaluated its application in
      extrusion to enhance fibre content of the final product. The pomace had low fat
      (0.61%) and high dietary fibre (45.22%), showing its potential for fibre
      enrichment of nutritionally poor products, as some extruded snacks. Results also
      showed low microbiological counts, water activity, and pH indicating good
      microbiological quality and low risk of physicochemical deterioration. During
      extrusion, pomace (0%, 10.5% and 21%), moisture (14%, 15% and 16%) and
      temperature (140 and 160 degrees C) were evaluated. The PP addition decreased
      expansion and luminosity; while increasing redness of the extrudates compared to
      the control (0% pomace/14% moisture/140 degrees C). When hardness, yellowness,
      water absorption, and bulk density were compared to the control, there was no
      effect (p>0.05) of 10.5% PP addition on the extrudates, indicating that, at this
      level, PP could be added without affecting the properties of the final extruded
      product.

PMID- 24912692
TI  - Simplified sample treatment for the determination of total concentrations and
      chemical fractionation forms of Ca, Fe, Mg and Mn in soluble coffees.
AB  - A simpler, and faster than wet digestion, sample treatment was proposed prior to
      determination of total concentrations for selected macro- (Ca, Mg) and
      microelements (Fe, Mn) in soluble coffees by flame atomic absorption
      spectrometry. Samples were dissolved in water and acidified with HNO3. Precision
      was in the range 1-4% and accuracy was better than 2.5%. The method was used in
      analysis of 18 soluble coffees available on the Polish market. Chemical
      fractionation patterns for Ca, Fe, Mg and Mn in soluble coffees, as consumed,
      using a two-column solid-phase extraction method, determined Ca, Mg and Mn were
      present predominantly as cations (80-93% of total content). This suggests these
      elements are likely to be highly bioaccessible.

PMID- 24912693
TI  - The effect of High Pressure and High Temperature processing on carotenoids and
      chlorophylls content in some vegetables.
AB  - The effect of High Pressure (HP) and High Pressure High Temperature (HPHT)
      processing on carotenoid and chlorophyll content of six vegetables was evaluated.
      In general, carotenoid content was not significantly influenced by HP or HPHT
      treatments (625 MPa; 5 min; 20, 70 and 117  degrees C). Regarding chlorophylls,
      HP treatment caused no degradation or slight increases, while HPHT processes
      degraded both chlorophylls. Chlorophyll b was more stable than chlorophyll a at
      70  degrees C, but both of them were highly degraded at 117  degrees C. HPHT
      treatment at 117  degrees C provided products with a good retention of
      carotenoids and colour in the case of red vegetables. Even though the carotenoids
      also remained in the green vegetables, their chlorophylls and therefore their
      colour were so affected that milder temperatures need to be applied. As an
      industrial scale equipment was used, results will be useful for future industrial
      implementation of this technology. 

PMID- 24912694
TI  - Metabolic variation and antioxidant potential of Malus prunifolia (wild apple)
      compared with high flavon-3-ol containing fruits (apple, grapes) and beverage
      (black tea).
AB  - Secondary metabolic variation of wild apple (Malus prunifolia) was compared with
      fruits that contained high flavan-3-ol like grapes (GR), apple (App) and the
      beverage, black tea (BT). The polyphenol contents in wild apple was higher than
      in GR and App but less than BT. The identified phenolic acids (gallic,
      protocatechuic, chlorogenic, p-coumaric and ferulic acids) and flavonoids
      (quercetin and myricetin) indicate that wild apple was higher than that of App.
      Among all the samples, BT had highest antioxidant potential in terms of 2,2'
      Azinobis (3-thylbenzothiazoline-6-sulfonic acid) diammonium salt (95.36%), metal
      chelating (45.36%) and phosphomolybdenum activity (95.8 mg/g) because of the high
      flavan-3-ol content. The gallic acid and epigallocatechin gallate were highly
      correlated with antioxidant potential and these metabolites levels are higher in
      wild apple than that of App. Wild apples being a non-commercial natural source, a
      detailed study of this plant will be helpful for the food additive and
      preservative industry.

PMID- 24912695
TI  - Post-harvest UV-B irradiation induces changes of phenol contents and
      corresponding biosynthetic gene expression in peaches and nectarines.
AB  - In the present study the possibility of enhancing phenolic compound contents in
      peaches and nectarines by post-harvest irradiation with UV-B was assessed. Fruits
      of 'Suncrest' and 'Babygold 7' peach and 'Big Top' nectarine cultivars were
      irradiated with UV-B for 12 h, 24 h and 36 h. Control fruits underwent the same
      conditions but UV-B lamps were screened by benzophenone-treated polyethylene
      film. The effectiveness of the UV-B treatment in modulating the concentration of
      phenolic compounds and the expression of the phenylpropanoid biosynthetic genes,
      was genotype-dependent. 'Big Top' and 'Suncrest' fruits were affected by
      increasing health-promoting phenolics whereas in 'Babygold 7' phenolics decreased
      after UV-B irradiation. A corresponding trend was exhibited by most of tested
      phenylpropanoid biosynthesis genes. Based on these results UV-B irradiation can
      be considered a promising technique to increase the health-promoting potential of
      peach fruits and indirectly to ameliorate the aesthetic value due to the higher
      anthocyanin content.

PMID- 24912696
TI  - Measuring protection of aromatic wine thiols from oxidation by competitive
      reactions vs wine preservatives with ortho-quinones.
AB  - Quinones are central intermediates in wine oxidation that can degrade the quality
      of wine by reactions with varietal thiols, such as 3-sulfanylhexanol, decreasing
      desirable aroma. Protection by wine preservatives (sulphur dioxide, glutathione,
      ascorbic acid and model tannin, phloroglucinol) was assessed by competitive
      sacrificial reactions with 4-methyl-1,2-benzoquinone, quantifying products and
      ratios by HPLC-UV-MS. Regioselectivity was assessed by product isolation and
      identification by NMR spectroscopy. Nucleophilic addition reactions compete with
      two electron reduction of quinones by sulphur dioxide or ascorbic acid, and both
      routes serve as effective quenching pathways, but minor secondary products from
      coupled redox reactions between the products and reactants are also observed. The
      wine preservatives were all highly reactive and thus all very protective against
      3-sulfanylhexanol loss to the quinone, but showed only additive antioxidant
      effects. Confirmation of these reaction rates and pathways in wine is needed to
      assess the actual protective action of each tested preservative. 

PMID- 24912697
TI  - Matrix-normalised quantification of species by threshold-calibrated competitive
      real-time PCR: allergenic peanut in food as one example.
AB  - A novel method to quantify species or DNA on the basis of a competitive
      quantitative real-time polymerase chain reaction (cqPCR) was developed.
      Potentially allergenic peanut in food served as one example. Based on an internal
      competitive DNA sequence for normalisation of DNA extraction and amplification,
      the cqPCR was threshold-calibrated against 100mg/kg incurred peanut in milk
      chocolate. No external standards were necessary. The competitive molecule
      successfully served as calibrator for quantification, matrix normalisation, and
      inhibition control. Although designed for verification of a virtual threshold of
      100mg/kg, the method allowed quantification of 10-1,000 mg/kg peanut incurred in
      various food matrices and without further matrix adaption: On the basis of four
      PCR replicates per sample, mean recovery of 10-1,000 mg/kg peanut in chocolate,
      vanilla ice cream, cookie dough, cookie, and muesli was 87% (range: 39-147%) in
      comparison to 199% (range: 114-237%) by three commercial ELISA kits.

PMID- 24912698
TI  - Direct-multiplex PCR assay for meat species identification in food products.
AB  - This is the first time that direct PCR - DNA amplification without prior DNA
      extraction - was successfully developed and fully validated for rapid and
      economical simultaneous identification of six commonly consumed meat species. To
      achieve this, six species-specific primers were selected from previous reports
      and newly designed from the mitochondrial cytochrome b (cyt b), cytochrome
      oxidase I (COI), and 12s rRNA gene. The assay generated PCR products of 100, 119,
      133, 155, 253, and 311 bp for pork, lamb/mutton, chicken, ostrich meat, horsemeat
      and beef, respectively. Validation showed that the assay is robust, rapid,
      economical, reproducible, specific, and sensitive down to 12,500 mitochondrial
      copy (equating to seven fg). It could be used with a variety of raw meats and
      products, including highly degraded and processed food samples. This proposed
      method will be greatly beneficial to the consumers, food industry, and law
      enforcement.

PMID- 24912699
TI  - Thermal edible oil evaluation by UV-Vis spectroscopy and chemometrics.
AB  - Edible oils such as colza, corn, sunflower, soybean and olive were analysed by UV
      Vis spectroscopy and Multivariate Curve Resolution with Alternating Least Squares
      (MCR-ALS). When vegetable oils were heated at high temperatures (frying),
      oxidation products were formed which were harmful to human health in addition to
      degrading the antioxidants present, and this study aimed to evaluate tocopherol
      (one antioxidant present in oils) and the behaviour of oxidation products in
      edible oils. The MCR-ALS results showed that the degradation started at 110
      degrees C and 85 degrees C, respectively, for sunflower and colza oils, while
      tocopherol concentration decreased and oxidation products increased starting at
      70 degrees C in olive oil. In soybean and corn oils, tocopherol concentration
      started to decrease and oxidation products increased at 50 degrees C. The results
      suggested that sunflower, colza and olive oils offered more resistance to
      increasing temperatures, while soybean and corn oils were less resistant.

PMID- 24912700
TI  - Smart phone: a popular device supports amylase activity assay in fisheries
      research.
AB  - Colourimetric determinations of amylase activity were developed based on a
      standard dinitrosalicylic acid (DNS) staining method, using maltose as the
      analyte. Intensities and absorbances of red, green and blue (RGB) were obtained
      with iPhone imaging and Adobe Photoshop image analysis. Correlation of green and
      analyte concentrations was highly significant, and the accuracy of the developed
      method was excellent in analytical performance. The common iPhone has sufficient
      imaging ability for accurate quantification of maltose concentrations. Detection
      limits, sensitivity and linearity were comparable to a spectrophotometric method,
      but provided better inter-day precision. In quantifying amylase specific activity
      from a commercial source (P>0.02) and fish samples (P>0.05), differences compared
      with spectrophotometric measurements were not significant. We have demonstrated
      that iPhone imaging with image analysis in Adobe Photoshop has potential for
      field and laboratory studies of amylase. 

PMID- 24912701
TI  - Antioxidant enzymes and fatty acid composition as related to disease resistance
      in postharvest loquat fruit.
AB  - Two cultivars of loquat fruit were stored at 20 degrees C for 10days to
      investigate the relationship between disease resistance, and fatty acid
      composition and activities of endogenous antioxidant enzymes. The results showed
      that decay incidence increased with storage time in both cultivars. A
      significantly lower disease incidence was observed in 'Qingzhong' fruit than in
      'Fuyang', suggesting 'Qingzhong' had increased disease resistance. Meanwhile,
      'Qingzhong' fruit also had lower levels of superoxide radical and hydrogen
      peroxide, and lower lipoxygenase activity, but higher levels of linolenic and
      linoleic acids and higher activities of catalase (CAT) and ascorbate peroxidase
      (APX) compared with 'Fuyang'. These results suggest that the higher levels of
      linolenic and linoleic acids and the higher activity of CAT and APX have a role
      in disease resistance of postharvest loquat fruit.

PMID- 24912702
TI  - Protein and amino acid composition of select wild legume species of tribe Fabeae.
AB  - The nutritional characteristics of seed proteins of 50 Spanish wild taxa of
      Lathyrus, Lens, Pisum and Vicia have been compared. The highest average protein
      richness and the in vitro protein digestibility have been observed in the genus
      Vicia and Lens, respectively, whereas the genus Pisum showed the lowest protein
      digestibility corrected amino acid score. Using the K-means algorithm three
      clearly distinguished groups of taxa have been established in relation to their
      essential amino acid contents, protein richness, digestibility and nutritional
      parameters. The most adequate protein profile was observed in the taxa of group
      1. This group includes four taxa of genus Lathyrus and nine taxa of genus Vicia.
      It should be noted that seven of the thirteen taxa included in this group have
      never been used as crops. 

PMID- 24912703
TI  - Obtaining lipases from byproducts of orange juice processing.
AB  - The presence of lipases was observed in three byproducts of orange juice
      processing: peel, core and frit. The enzymes were characterised biochemically
      over a wide pH range from neutral (6-7) to alkaline (8-9). The optimal
      temperature for the activity of these byproducts showed wide range at 20 degrees
      C to 70 degrees C, indicating fairly high thermostability. The activities were
      monitored on p-NP-butyrate, p-NP-laurate and p-NP-palmitate. For the first time,
      lipase activity was detected in these residues, reaching 68.5 lipase U/g for the
      crude extract from fractions called frit.

PMID- 24912704
TI  - Enzymatic process for the fractionation of baker's yeast cell wall (Saccharomyces
      cerevisiae).
AB  - beta-Glucans, homopolymers of glucose, are widespread in many microorganisms,
      mushrooms and plants. They have attracted attention because of their bioactive
      and medicinal functions. One important source of beta-glucans is the cell wall of
      yeasts, especially that of baker's yeast Saccharomyces cerevisiae. Several
      processes for the isolation of beta-glucans, using alkali, acid or a combination
      of both, result in degradation of the polymeric chains. In this paper, we have an
      enzymatic process for the isolation of glucans from yeast cell walls. As a
      result, beta-glucans were obtained in a yield of 18.0% of the original ratio in
      the yeast cell walls. Therefore, this isolation process gave a better yield and
      higher beta-glucan content than did traditional isolation methods. Furthermore,
      results showed that each extraction step of beta-glucan had a significant effects
      on its chemical properties. 

PMID- 24912705
TI  - Structure and property modification of an oligochitosan-glycosylated and
      crosslinked soybean protein generated by microbial transglutaminase.
AB  - The impacts of oligochitosan glycosylation and crosslinking on the structure and
      properties of a soybean protein were investigated. The reaction was carried out
      by transglutaminase with 10 kU kg(-1) protein at pH 7.5 and 37 degrees C for 3h,
      under a protein content of 40 gl(-1) and a molar ratio of acyl donor to
      oligochitosan acceptor of 1:3. The modified protein contained glucosamine at a
      concentration of 12.1 g kg(-1) protein. Electrophoresis and infrared spectroscopy
      analysis confirmed the modified protein to be crosslinked and glycosylated.
      Circular dichroism analysis showed the modified protein possessed a decreased
      alpha-helix and beta-structure. The modified protein exhibited lower surface
      hydrophobicity and emulsifying activity but higher emulsion stability than the
      soybean protein, it also had better water and oil binding capacity (12.2g and 3.5
      ml g(-1) protein, respectively), and could form a thicker protein outer layer in
      the oil droplets in emulsion. Transglutaminase-induced oligochitosan
      glycosylation and crosslinking is thus able to modify soybean proteins.

PMID- 24912706
TI  - Characterisation and immunomodulating activities of exo-polysaccharides from
      submerged cultivation of Hypsizigus marmoreus.
AB  - Exo-polysaccharides were purified and characterized from the fermentation broth
      of Hypsizigus marmoreus, a popular edible mushroom consumed in Asia. Among them,
      B-I-I and B-II-I exhibited potent complement fixating activity, meanwhile, B-N-I,
      B-I-I, B-II-I and B-II-II exhibited significant macrophage stimulating activity.
      Molecular weights of the four exo-polysaccharides were determined to be 6.3, 120,
      150 and 11 kDa respectively. Molecular characterisation showed that B-N-I is
      basically an alpha-1->4 glucan, with branches on C6; B-I-I is a heavily branched
      alpha-mannan with 1->2 linked main chain. B-II-I and B-II-II, have a backbone of
      rhamno-galacturonan with 1->2 linked l-rhamnose interspersed with 1->4 linked
      galacturonic acid. Structure-activity relationship analysis indicated that
      monosaccharide compositions, molecular weight, certain structural units (rhamno
      galacturonan type I and arabinogalactan type II) are the principal factors
      responsible for potent complement fixating and macrophage-stimulating activities.
      Their immunomodulating activities may, at least partly, explain the health
      benefits of the mushroom.

PMID- 24912707
TI  - Effect of sulphydryl reagents on the heat stability of whey protein isolate.
AB  - The effects of sulphydryl (-SH) reagents on protein aggregation reactions in
      heated whey protein isolate (WPI) and pure alpha-lactalbumin (alpha-La) were
      investigated. In contrast to its previously reported effect with pure beta-Lg,
      dihydrolipoic acid (DHLA) markedly reduced the heat stability of WPI, especially
      the alpha-La component, which aggregated much more readily in the presence of
      DHLA than in WPI alone. Whilst pure alpha-La is quite stable to heat, it is much
      less stable in the presence of DHLA. An effect similar to DHLA was observed with
      reduced glutathione (GSH). N-ethylmaleimide (NEM), and to a lesser extent,
      dithio(bis)-p-nitrobenzoate (DTNB), improved the heat stability of WPI; these
      reagents had little effect on alpha-La.

PMID- 24912708
TI  - Study of the effects of proline, phenylalanine, and urea foliar application to
      Tempranillo vineyards on grape amino acid content. Comparison with commercial
      nitrogen fertilisers.
AB  - The aim of this work was to study the influence of foliar application of
      different nitrogen sources on grape amino acid content. The nitrogen sources
      applied to Tempranillo grapevines were proline, phenylalanine, urea, and two
      commercial nitrogen fertilisers, both without and with amino acids in their
      formulations. All treatments were applied at veraison and one week later. Proline
      treatment did not affect the must nitrogen composition. However, phenylalanine
      and urea foliar application enhanced the plants' synthesis of most of the amino
      acids, producing similar effects. In addition, the spray of commercial nitrogen
      fertilisers over leaves also induced a rise in grape amino acid concentrations
      regardless of the presence or absence of amino acids in their formulation. The
      most effective treatments were phenylalanine and urea followed by nitrogen
      fertilisers. This finding is of oenological interest for improved must nitrogen
      composition, ensuring better fermentation kinetics and most likely enhancing wine
      quality.

PMID- 24912709
TI  - Radiation-treated ready-to-eat (RTE) chicken breast Adobo for immuno-compromised
      patients.
AB  - Usually in hospitals low-bacterial diets are served to immuno-compromised
      patients (ICPs). However, low-bacterial diets still pose a high risk of microbial
      infections and limit the food selection of the patients. Thus, pathogen-free
      dishes must be made available. This study presents the development of pathogen
      free ready-to-eat (RTE) Filipino ethnic food chicken breast Adobo, sterilized by
      exposure to high-dose gamma rays (25 kGy) in combination with conventional
      treatments. Frozen vacuum-packed samples artificially inoculated with Escherichia
      coli, Listeria monocytogenes, Bacillus cereus, Staphylococcus aureus and
      Salmonella enterica subsp. enterica serovar Typhimurium, were exposed to 25 kGy
      gamma radiation for complete sterilization. Microbial quality and sterility of
      the samples were analysed following 15, 30, and 60 days of storage at -4 degrees
      C. The effects of high-dose gamma irradiation on the nutritional quality and
      sensory characteristics of RTE chicken breast Adobo were also evaluated.

PMID- 24912710
TI  - Tackling the challenge of selective analytical clean-up of complex natural
      extracts: the curious case of chlorophyll removal.
AB  - Alkaline saponification is often used to remove interfering chlorophylls and
      lipids during carotenoids analysis. However, saponification also hydrolyses
      esterified carotenoids and is known to induce artifacts. To avoid carotenoid
      artifact formation during saponification, Larsen and Christensen (2005) developed
      a gentler and simpler analytical clean-up procedure involving the use of a strong
      basic resin (Ambersep 900 OH). They hypothesised a saponification mechanism based
      on their Liquid Chromatography-Photodiode Array (LC-PDA) data. In the present
      study, we show with LC-PDA-accurate mass-Mass Spectrometry that the main
      chlorophyll removal mechanism is not based on saponification, apolar adsorption
      or anion exchange, but most probably an adsorption mechanism caused by H-bonds
      and dipole-dipole interactions. We showed experimentally that esterified
      carotenoids and glycerolipids were not removed, indicating a much more selective
      mechanism than initially hypothesised. This opens new research opportunities
      towards a much wider scope of applications (e.g. the refinement of oils rich in
      phytochemical content). 

PMID- 24912711
TI  - Influence of ingredients and chemical components on the quality of Chinese
      steamed bread.
AB  - Chinese steamed bread (CSB) is a staple food in China since ancient time. The
      basic ingredients include wheat flour, yeast/sourdough, and water. Current
      consumer trends urge the production of CSB on a large scale as well as the
      formulation of healthier CSB with specific nutritional benefits. This requires a
      better definition of the relationship between the properties of
      ingredients/chemical components and CSB quality. This review summarises the
      recent advances in understanding the roles of basic and optional ingredients and
      their chemical components in the appearance, textural, sensory, and shelf-life
      properties of CSB, and provides suggestions for further research to match the
      current trends. 

PMID- 24912712
TI  - Combined effect of pH and high temperature on the stability and antioxidant
      capacity of two anthocyanins in aqueous solution.
AB  - The stability of two cyanidin-based anthocyanins from black rice in an aqueous
      system containing them with a pH range of 2.2-6.0 was investigated at
      temperatures ranging from 100 to 165 degrees C. Within these pH and temperature
      ranges, the stability of the two anthocyanins was found to decrease gradually
      with increasing pH. The lowest (8.99*10(-4)s(-1)) and highest (0.120s(-1))
      degradation rate constants for cyanidin-3-glucoside were obtained at pH 2.2 & 100
      degrees C and pH 6.0 & 165 degrees C, respectively, whereas those for cyanidin-3
      rutinoside were 5.33*10(-4)s(-1) at pH 2.2 & 100 degrees C and 7.39*10(-2)s(-1)
      at pH 5.0 & 165 degrees C, respectively. Antioxidant capacity analysis was
      conducted on thermally processed anthocyanin solutions to further evaluate the
      effects of pH and thermal treatment on the anthocyanins. The total antioxidant
      capacity of samples after thermal treatments under various pHs was found to
      remain at a similar level.

PMID- 24912713
TI  - Design and straightforward synthesis of novel galloyl phytosterols with excellent
      antioxidant activity.
AB  - Novel galloyl phytosterols were rationally designed by incorporation of gallic
      acid into phytosterols through straightforward esterification. The esterification
      was successfully achieved by coupling of gallic acid and phytosterols through a
      mild chemical Steglich esterification reaction that is more straightforward than
      the enzymatic method. The identity of the newly synthesized galloyl phytosterols
      was confirmed by NMR, HPLC-MS and IR spectroscopies. Further evaluation of the
      novel galloyl phytosterols with radical scavenging, ferrous ion chelating, and
      Rancimat methods revealed its excellent antioxidant activities that are
      comparable to the most potent fat-soluble antioxidants. This novel antioxidant
      offers an intriguing solution for naturally derived antioxidants and will have
      great potential application as antioxidant in food industry. The methods
      developed in this study will be valuable for development of other phenolic
      phytosterols. 

PMID- 24912715
TI  - Profiling of nonvolatiles in whiskeys using ultra high pressure liquid
      chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS).
AB  - Commercial samples of 63 American whiskeys, including bourbon whiskeys, Tennessee
      whiskeys, rye whiskeys and other blended whiskeys were analysed using ultra high
      pressure liquid chromatography (UHPLC) coupled with quadrupole time-of-flight
      (QTOF) mass spectrometry (MS). The non-volatile composition of the whiskeys was
      used to model differences among the samples using discriminant analysis. The
      blended American whiskeys were readily distinguished from the remaining types.
      Additionally, most Tennessee whiskeys could be differentiated from bourbon and
      rye whiskeys. Similarly, younger (<4 years old) and older (>8 years old) whiskeys
      could be separated. The compounds important for differentiating among these
      whiskeys included wood derived phenolic compounds, lignan derived compounds and
      several C8 and larger lipids. A number of additional compounds differentiated the
      whiskeys but could not be identified using MS and MS/MS data alone.

PMID- 24912714
TI  - Quinoa seeds leach phytoecdysteroids and other compounds with anti-diabetic
      properties.
AB  - Quinoa (Chenopodium quinoa Willd.) contains high levels of biologically active
      phytoecdysteroids, which have been implicated in plant defense from insects, and
      have shown a range of beneficial pharmacological effects in mammals. We
      demonstrated that the most prevalent phytoecdysteroid, 20-hydroxyecdysone (20HE),
      was secreted (leached) from intact quinoa seeds into water during the initial
      stages of seed germination. Leaching efficiency was optimized by ethanol
      concentration (70% ethanol), temperature (80 degrees C), time (4h), and solvent
      ratio (5 ml/g seed). When compared to extraction of macerated seeds, the leaching
      procedure released essentially all the 20HE available in the seeds (491 MUg/g
      seed). The optimized quinoa leachate (QL), containing 0.86% 20HE, 1.00% total
      phytoecdysteroids, 2.59% flavonoid glycosides, 11.9% oil, and 20.4% protein,
      significantly lowered fasting blood glucose in obese, hyperglycemic mice.
      Leaching effectively releases and concentrates bioactive phytochemicals from
      quinoa seeds, providing an efficient means to produce a food-grade mixture that
      may be useful for anti-diabetic applications.

PMID- 24912716
TI  - Effect of water content and temperature on inactivation kinetics of myrosinase in
      broccoli (Brassica oleracea var. italica).
AB  - Broccoli belongs to the Brassicaceae plant family consisting of widely eaten
      vegetables containing high concentrations of glucosinolates. Enzymatic hydrolysis
      of glucosinolates by endogenous myrosinase (MYR) can form isothiocyanates with
      health-promoting activities. The effect of water content (WC) and temperature on
      MYR inactivation in broccoli was investigated. Broccoli was freeze dried
      obtaining batches with WC between 10% and 90% (aw from 0.10 to 0.96). These
      samples were incubated for various times at different temperatures (40-70 degrees
      C) and MYR activity was measured. The initial MYR inactivation rates were
      estimated by the first-order reaction kinetic model. MYR inactivation rate
      constants were lower in the driest samples (10% WC) at all studied temperatures.
      Samples with 67% and 90% WC showed initial inactivation rate constants all in the
      same order of magnitude. Samples with 31% WC showed intermediate initial
      inactivation rate constants. These results are useful to optimise the conditions
      of drying processes to produce dried broccoli with optimal MYR retention for
      human health. 

PMID- 24912717
TI  - Enzymatic hydrolysis of steryl glycosides for their analysis in foods.
AB  - Steryl glycosides (SG) contribute significantly to the total intake of
      phytosterols. The standard analytical procedure involving acid hydrolysis fails
      to reflect the correct sterol profile of SG due to isomerization of some of the
      labile sterols. Therefore, various glycosylases were evaluated for their ability
      to hydrolyse SG under milder conditions. Using a pure SG mixture in aqueous
      solution, the highest glycolytic activity, as demonstrated by the decrease in SG
      and increase in free sterols was achieved using inulinase preparations (decrease
      of >95%). High glycolytic activity was also demonstrated using hemicellulase
      (63%). The applicability of enzymatic hydrolysis using inulinase preparations was
      further verified on SG extracted from foods. For example in potato peel Delta(5)
      avenasteryl glucoside, a labile SG, was well preserved and contributed 26.9% of
      the total SG. Therefore, enzymatic hydrolysis is suitable for replacing acid
      hydrolysis of SG in food lipid extracts to accurately determine the sterol
      profile of SG. 

PMID- 24912718
TI  - Some qualitative properties of different monofloral honeys.
AB  - In this study, physico-chemical properties of honeys samples obtained from
      different locations of Turkey were investigated. Moisture, diastase activity,
      Hydroxy Methyl Furfural (HMF), viscosity, acidity, total glucose+fructose,
      protein and ash contents of honey samples ranged from 17.1% to 20.0%, 10.9 to
      17.9, 1.34 to 31.28 mg/kg, 2.48 to 8.42 Pa s, 18.2 to 47.5 meq/kg, 51.31% to
      68.30%, 0.60% to 0.99% and 0.01% to 0.12%, respectively. The colour parameters,
      namely L, a, b changed between 24.56 and 34.16, 0.08 and 0.67, 0.60 and 5.09,
      respectively. The magnesium was found at high level in all samples. Cornflower
      honey sample had the highest phenolic content (645.85 mg/100 g). While
      antioxidant activity of cedar honey sample is found at the highest level, thorn
      honey sample showed the least antioxidant activity. In general, dark coloured
      honey samples had higher phenolic content levels and antioxidant activity than
      the light coloured honey samples.

PMID- 24912719
TI  - Effect of repeated retrogradation on structural characteristics and in vitro
      digestibility of waxy potato starch.
AB  - The effects of repeated retrogradation (RR) treatment on the structural
      characteristics and in vitro digestibility of waxy potato starch were
      investigated. The cycling times of RR ranging from 1 to 5 were designated as RR
      1, RR-2, RR-3, RR-4, and RR-5, respectively. A maximum SDS content (40.41%) was
      obtained by RR-2 treatment with the time interval of 48h. RR-2-treated starch
      product exhibited a narrower melting temperature range, a higher onset
      temperature and a lower melting enthalpy compared with RR-1 treatment. Compared
      with native starch, X-ray diffraction patterns of treated starches were altered
      from B-type to C-type. The variation in relative crystallinity of RR-treated
      starch products was consistent with that in melting enthalpy. Moreover, compared
      with RR-1-treated starch, a large number of cavities were observed on the surface
      of RR-2-treated starch product with a time interval of 48h, whereas more smooth
      regions were found on the surface of RR-5-treated starch product. This study
      suggested that structural changes of waxy potato starch treated with different
      cycling times of RR significantly affected the digestibility.

PMID- 24912720
TI  - Inhibitory effect of morin on tyrosinase: insights from spectroscopic and
      molecular docking studies.
AB  - Tyrosinase is a key enzyme in the production of melanin in the human body,
      excessive accumulation of melanin can lead to skin disorders. Morin is an
      important bioactive flavonoid compound widely distributed in plants and foods of
      plant origin. In this study, the inhibitory kinetics of morin on tyrosinase and
      their binding mechanism were determined using spectroscopic and molecular docking
      techniques. The results indicate that morin reversibly inhibited tyrosinase in a
      competitive manner through a multi-phase kinetic process. Morin was found to bind
      to tyrosinase at a single binding site mainly by hydrogen bonds and van der Waals
      forces. Analysis of circular dichroism spectra revealed that the binding of morin
      to tyrosinase induced rearrangement and conformational changes of the enzyme.
      Moreover, molecular docking results suggested that morin competitively bound to
      the active site of tyrosinase with the substrate levodopa. 

PMID- 24912721
TI  - Optimisation and validation of analytical methods for the simultaneous extraction
      of antioxidants: application to the analysis of tomato sauces.
AB  - In the present study, simultaneous extraction of natural antioxidants (phenols
      and carotenoids) in complex matrices, such as tomato sauces, is presented. The
      tomato sauce antioxidant compounds studied were the phenolics hydroxytyrosol,
      from virgin olive oil, quercetin and its derivatives, from onions, and quercetin
      rutinoside as well as the carotenoid, lycopene (cis and trans), from tomatoes.
      These antioxidant compounds were extracted simultaneously with n
      hexane/acetone/ethanol (50/25/25, v/v/v). The phenolics were analysed by ultra
      performance liquid chromatography coupled with tandem mass spectrometry (UPLC
      MS/MS), and lycopene (cis- and trans-forms) was analysed using high-performance
      liquid chromatography coupled to a diode array detector (HPLC-DAD). After
      studying the parameters of these methods, they were applied to the analysis of
      virgin olive oil, fresh onion, tomato concentrate and tomato powder, and
      commercial five tomato sauces. Subsequently, the results obtained in our
      laboratory were compared with those from the Gallina Blanca Star Group
      laboratory. 

PMID- 24912722
TI  - Identification of new flavonols in hybrid grapes by combined liquid
      chromatography-mass spectrometry approaches.
AB  - Grape flavonols are involved in the phenomenon of copigmentation in red wines.
      These compounds are characterised by nutraceutical properties, have antioxidant
      activity and are studied for chemotaxonomy of grapes. In general, hybrid grapes
      are characterised by presence of polyphenols often qualitatively and
      quantitatively different from Vitis vinifera varieties. In this work, flavonols
      of 34 hybrid grape varieties (22 red and 12 white) produced by crossing of V.
      vinifera, Vitis riparia, Vitis labrusca, Vitis lincecumii and Vitis rupestris
      species, were studied. Compounds were characterised by combining different liquid
      chromatography/mass spectrometry (LC/MS) methods: precursor-ion and neutral-loss
      multiple-reaction-monitoring (MRM), and high-resolution mass spectrometry. Twenty
      four glycoside flavonols were identified, including 4 quercetin, 5 myricetin, 4
      kaempferol, 3 isorhamnetin, 2 laricitrin, 3 syringetin and 3 dihydroflavonol
      derivatives; myricetin hexoside-glucuronide, myricetin O-di-hexoside, syringetin
      O-di-hexoside, isorhamnetin rutinoside and kaempferol rutinoside were found in
      grape for the first time. Statistical analysis (PCA and cluster analysis) divided
      the samples in four groups on the basis of their flavonol profiles. 

PMID- 24912723
TI  - HPLC and UPLC methods for the determination of zearalenone in noodles, cereal
      snacks and infant formula.
AB  - High-performance liquid chromatography (HPLC) and ultra-performance liquid
      chromatography (UPLC) were compared to validate a method for determination of
      zearalenone (ZON) in noodles, cereal snacks, and infant formulas. The limits of
      detection and quantification in HPLC and UPLC were found to be 4.0 and 13.0 MUg
      kg(-1) and 2.5 and 8.3 MUg kg(-1), respectively. The average recoveries of ZON by
      HPLC and UPLC ranged from 79.1% to 105.3% and from 85.1% to 114.5%, respectively.
      The measurement uncertainties of the two methods for ZON determination were
      within the maximum standard uncertainty. The two methods showed that the levels
      of ZON in 163 naturally contaminated samples ranged from 4.3 to 8.3 MUg kg(-1) by
      HPLC and 3.1 to 17.6 MUg kg(-1) by UPLC. These findings indicate that either
      method is suitable for the determination of ZON in noodles, cereal snacks, and
      infant formulas, but UPLC gives faster results with better sensitivity.

PMID- 24912724
TI  - Effect of vine foliar treatments on the varietal aroma of Monastrell wines.
AB  - The effects of four vine treatments, comprising the application of eugenol and
      guaiacol (individually or as a mixture) or whiskey lactones on the concentration
      of glycosidically bound aroma precursors, determined as glycosyl glucose content
      by HPLC-IR, in Monastrell grapes and their wines were studied. The impact of
      treatments on the free varietal wine aroma determined by SBSE-GC-MS and
      descriptive analysis after alcoholic and malolactic fermentations and six months
      of ageing were also determined. A synergistic effect was observed between the
      eugenol and guaiacol on the glycosidically bound aroma precursor fraction. The
      rate of release of such aroma precursors was time and treatment dependent. The
      impact on wines varietal aroma at the end of the alcoholic fermentation was
      reduced by treatments, whereas the opposite effect was observed in the following
      samplings. At a sensory level, the wood/oak notes were appreciated in all wines;
      however, the typicity of the Monastrell variety was especially enhanced at the
      end of the malolactic fermentation, in the wines from whiskey lactone treatment. 

PMID- 24912725
TI  - The use of Vis/NIRS and chemometric analysis to predict fruit defects and
      postharvest behaviour of 'Nules Clementine' mandarin fruit.
AB  - The use of chemometrics to analyse Vis/NIRS signal collected from intact 'Nules
      Clementine' mandarin fruit at harvest, to predict the rind physico-chemical
      profile after eight weeks postharvest was explored. Vis/NIRS signals of 150 fruit
      were obtained immediately after harvest. Reference data on the rind were obtained
      after eight-week storage, including colour index (CI), rind dry matter (DM), and
      concentration of sugars. Partial least squares (PLS) regression was applied to
      develop models. Principal component analysis (PCA) followed by PLS-discriminant
      analysis (PLS-DA) were used to classify fruit according to canopy position.
      Optimal PLS model performances for DM, sucrose, glucose and fructose were
      obtained using multiple scatter correction pre-processing, showing respective
      residual predictive deviation (RPD) of 3.39, 1.75, 2.19 and 3.08. Clusters of
      sample distribution in the PCA and PLS-DA models based on canopy position were
      obtained. The results demonstrated the potential applications of Vis/NIRS to
      predict postharvest behaviour of mandarin fruit.

PMID- 24912726
TI  - Phenolic profiling of Veronica spp. grown in mountain, urban and sandy soil
      environments.
AB  - Veronica (Plantaginaceae) genus is widely distributed in different habitats. The
      phenolic compounds of Veronica montana, Veronica polita and Veronica spuria were
      tentatively identified by HPLC-DAD-ESI/MS. The phenolic profiles showed that
      flavones were the major compounds (V. montana: 7 phenolic acids, 5 flavones, 4
      phenylethanoids and 1 isoflavone; V. polita: 10 flavones, 5 phenolic acids, 2
      phenylethanoids, 1 flavonol and 1 isoflavone; V. spuria: 10 phenolic acids, 5
      flavones, 2 flavonols, 2 phenylethanoids and 1 isoflavone). V. spuria possessed
      the highest contents in all groups of phenolic compounds, except flavones, which
      did not show differences among the assayed species. Overall, these species might
      be considered good sources of phenolic compounds for industrial or
      pharmacological applications.

PMID- 24912727
TI  - Influence of lactose on the diffusion of calcium ions at physiological
      temperature.
AB  - Mutual diffusion coefficients for calcium chloride (0.100 mol dm(-3)) in aqueous
      solutions containing lactose at various concentrations (from 0.005 to 0.200 mol
      dm(-3)) have been measured at 37 degrees C (physiological temperature), by using
      a conductimetric cell coupled to an automatic system to follow the diffusion.
      This cell uses an open-ended capillary method based on the measurement of the
      electrical resistance of a solution placed inside the capillaries at recorded
      times. The analysis of the CaCl2 diffusion coefficient values obtained suggests
      the presence of some CaCl2/lactose aggregates in the media, which are influenced
      by the temperature.

PMID- 24912728
TI  - Phenolic compounds and antioxidant capacity of virgin olive oil.
AB  - The characterisation of virgin olive oil from Arbequina, Carrasquena, Corniche,
      Manzanilla Cacerena, Morisca, Picual, and Verdial de Badajoz varieties according
      to the individual phenolic compounds at different ripening stage was carried out.
      In all olive oil varieties studied, secoiridoid derivatives were most abundant,
      followed by phenolic alcohols, flavonoids and phenolic acids. The secoiridoid
      derivatives of hydroxytyrosol were the most important complex phenols for Picual
      and Carrasquena, whereas the tyrosol derivatives were the major ones found in
      Manzanilla Cacerena, and Verdial de Badajoz. For secoiridoid derivatives of
      hydroxytyrosol and tyrosol, Arbequina was the oil variety showing the lowest
      concentration. Tyrosol, hydroxytyrosol, vanillic acid, p-cumaric acid, luteolin,
      and apigenin levels were greater in early harvested samples in almost all oils
      analysed. Antioxidant activity measurements (antiradical, lipid peroxide
      inhibition, H2O2 and NO scavenging) were also accomplished for the seven
      varieties in the first ripening stage.

PMID- 24912729
TI  - Tubal ligation in Catholic hospitals: a qualitative study of ob-gyns'
      experiences.
AB  - OBJECTIVE: Tubal sterilization remains one of the most commonly requested
      contraceptive methods in the United States. Catholic hospital policy prohibits
      all sterilizations, but this ban is not uniformly enforced. We conducted this
      study to assess obstetrician-gynecologists' beliefs and experiences with tubal
      ligation in Catholic hospitals. STUDY DESIGN: We interviewed 31 obstetrician
      gynecologists geographically dispersed throughout the US who responded to a
      national survey and agreed to be contacted for a follow-up interview or who were
      referred by colleagues from the survey sample. Twenty-seven had experienced
      working in a Catholic hospital. Interviews were open ended and guided by a
      semistructured instrument. Transcripts were thematically analyzed. RESULTS:
      Obstetrician-gynecologists disagreed with strict prohibition of sterilizations,
      especially when denying a tubal ligation placed the patient at increased medical
      risk. Cesarean delivery in Catholic hospitals raised frustration for obstetrician
      gynecologists when the hospital prohibited a simultaneous tubal ligation and,
      thus, sent the patient for an unnecessary subsequent surgery. Obstetrician
      gynecologists described some hospitals allowing tubal ligations in limited
      circumstances, but these workarounds were vulnerable to changes in enforcement.
      Some obstetrician-gynecologists reported that Catholic policy posed greater
      barriers for low-income patients and those with insurance restrictions.
      CONCLUSION: Obstetrician-gynecologists working in Catholic hospitals in this
      study did not share the Church's beliefs on sterilization. Research to understand
      patients' experiences and knowledge of their sterilization options is warranted
      in order to promote women's autonomy and minimize risk of harm. IMPLICATIONS
      STATEMENT: Tubal sterilization, even when medically indicated or in conjunction
      with cesarean delivery, is severely restricted for women delivering in Catholic
      hospitals. For women whose only access to hospital care is at a Catholic
      institution, religious policies can prevent them from receiving a desired
      sterilization and place them at risk for future undesired pregnancy.

PMID- 24912730
TI  - Efficacy and safety of rufinamide in children under four years of age with drug
      resistant epilepsies.
AB  - BACKGROUND: Studies on the efficacy and tolerability of rufinamide in infants and
      young children are scarce. Here we report on an open, retrospective, and
      pragmatic study about safety and efficacy of rufinamide in children aged less
      than four years, in terms of seizures types and epilepsy syndromes. METHODS:
      Forty children (mean age 39.5 months; range 22-48) were enrolled in the study.
      The mean follow-up period was 12.2 months (range 5-21). Rufinamide was initiated
      at a mean age of 26.7 months (range 12-42). Final rufinamide mean dosage was 31.5
      mg/kg/day if associated with valproic acid and 44.2 mg/kg/day if not. RESULTS:
      The highest seizure reduction rate was observed in the epileptic spasms (46%) and
      drop attacks (42%) groups. Seizure reduction was also observed in tonic seizures
      (35%) and in the focal seizure (30%) groups. In terms of epilepsy syndrome,
      rufinamide was effective in Lennox-Gastaut syndrome. Results were very poor for
      those affected by Dravet's syndrome. Globally, responder rate was 27.5%,
      including two (5%) patients seizure-free. Adverse reactions occurred in 37.5% of
      children and were mainly represented by vomiting, drowsiness, irritability, and
      anorexia. Discontinuation rate due to treatment-emergent adverse events was 15%.
      CONCLUSION: The present study concludes that rufinamide may be a safe and
      effective drug for a broad range of seizures and epilepsy syndromes in infants
      and young children and represents a valid therapeutic option in this population.

PMID- 24912731
TI  - Chromosomal aberrations in cerebral visual impairment.
AB  - BACKGROUND: Cerebral visual impairment (CVI) is a disorder in projection and/or
      interpretation of the visual input in the brain and accounts for 27% of the
      visually impaired children. AIM: A large cohort of patients with CVI was
      investigated in order to ascertain the relevance of chromosomal aberrations in
      the etiology of this disorder. METHODS: 607 patients with CVI and a visual acuity
      <=0.3 were assessed for the presence of a chromosomal aberration retrospectively.
      The observed aberrations were classified for pathogenicity. RESULTS: A total of
      98 chromosomal aberrations were found in 79 persons (13%) of the cohort. In nine
      persons it was not possible to classify the clinical implication of the
      aberration, due to lack of detailed information. In 70 persons it was possible to
      classify the aberration for causality: in 41 patients the aberration was
      associated with CVI, in 16 it was unknown and in 13 the aberration was unlikely
      to be associated with CVI. For four aberrations, present in 26 patients, the
      association with CVI has been reported before: trisomy 21, 1p36 deletion
      syndrome, 17p13.3 deletion syndrome (Miller-Dieker syndrome) and 22q13.3 deletion
      syndrome (Phelan-McDermid syndrome). The chromosomal aberrations in another 15
      patients were for the first time associated with CVI. CONCLUSIONS: Chromosomal
      aberrations associated with CVI were found in 7% (41/607) of patients, of which
      37% (15/41) have not been reported before in association with CVI. Therefore, in
      patients with CVI chromosomal investigations should be routinely performed to
      warrant a good clinical diagnosis and counseling.

PMID- 24912732
TI  - Anterior corpus callosotomy in school-aged children with Lennox-Gastaut syndrome:
      a prospective study.
AB  - AIMS: To compare outcomes of anterior corpus callosotomy (CCT) with anti
      epileptic drugs (AEDs) treatment in school-aged children with Lennox-Gastaut
      syndrome (LGS). METHODS: Sixty school-aged children with LGS were prospectively
      enrolled and divided into either the medicine or surgery group according the
      choice of the patients' caregivers. Cases in the medicine group were treated with
      multiple rational AEDs and patients in the surgery group underwent anterior CCT.
      Seizure control at 1-5 years after enrollment and changes of intelligence
      quotient (IQ) and quality of life (QOL) from pre-treatment to the 2-year follow
      up were compared between the two groups. RESULTS: The percentages of patients who
      were totally seizure-free in the surgery group were 17.4% at the 1-year follow
      up, 13.0% at the 2-year follow-up and 8.7% at the 5-year follow up, and the data
      for patients in the medicine group were 2.9%, 5.9% and 2.9%, respectively.
      Significant differences were found in total seizure control between the two
      groups at 1, 2, and 5-year follow-up (personal chi2 test). Significant
      differences were found in mean changes of IQ and overall QOL between the medicine
      and surgery groups at the 2-year follow-up, showing positive results for the
      surgery group, but these changes were not related to postoperative outcomes of
      seizure control (t-test). CONCLUSION: Anterior CCT is a promising treatment for
      school-aged children with LGS, and can present marked seizure control and
      improvement in QOL and IQ, all of which were significantly better than the
      effects of treatment with multiple AEDs.

PMID- 24912733
TI  - In vivo MRI visualization of parastomal mesh in a porcine model.
AB  - INTRODUCTION: After two-dimensional plane MRI-visible mesh implants could be
      successfully visualized in phantom and small animal model, the aim of the
      underlying study was to explore the feasibility of an MRI visualization of
      complex three-dimensional mesh geometry in close contact to the intestine. We
      therefore used a MR-visible three-dimensional intra-peritoneal stoma (IPST) mesh
      in a porcine model. MATERIALS AND METHODS: Laparoscopic terminal sigmoid
      colostomy has been done with implantation of a prophylactic MRI-visible IPST mesh
      in two animals. MRI investigations were done after 1 week, 6 months and in case
      of clinical impairment. These findings were compared to endoscopy and
      makroscopical and histological investigation of the preparation. RESULTS: The
      first animal has to be killed because of an ileus 4 weeks after operation. The
      second animal has to be killed after 7 weeks because of recurrent obstipation. In
      all cases MRI investigation could identify the IPST mesh and could clearly
      separate between mesh and intestine. MRI revealed a big bowl ileus due to a
      funnel dislocation in the first animal. In the second animal, MR diagnostic
      explored a functional stenosis because of a too small diameter of the central
      funnel in combination with sticky feces and distension of the terminal sigmoid
      before discharging into the funnel. Endoscopy, makroscopical and histological
      investigation of the preparation supported MRI findings. CONCLUSION: Although
      complicate clinical course was a diagnostic challenge exploring 3D implants such
      as IPST, visualization of this new MRI-visible IPST mesh could be proved and
      turned out as an effective diagnostic possibility. Further studies are necessary
      to analyze long-time effects such as shrinkage, mesh migration and tissue
      integration using MRI scanning.

PMID- 24912734
TI  - Endoscopic component separation for laparoscopic and open ventral hernia repair:
      a single institutional comparison of outcomes and review of the technique.
AB  - PURPOSE: To our knowledge, there are limited small case series reports on
      endoscopic component separation (ECS) and no single institutional study comparing
      the difference in outcomes between laparoscopic and open ventral hernia repairs
      following endoscopic component separation. METHODS: A single institutional
      retrospective review was performed, identifying 42 patients who underwent
      endoscopic component separation at a single institution by a single surgeon for
      ventral hernia repair with prosthesis from 2010 to 2013. Seventeen patients
      underwent subsequent open ventral hernia repair (OHR) and 25 underwent
      laparoscopic ventral hernia repair (LHR). Demographics, surgical factors, wound
      complications and hernia occurrence post-operatively were reviewed. RESULTS:
      Surgical factors/demographics were similar between groups. All patients achieved
      primary fascial and skin closure. Operative time for the laparoscopic group was
      significantly shorter than the open group (278 vs. 378 min; P = 0.0001), and
      there was a trend towards a shorter hospital stay in the laparoscopic group
      (laparoscopic, 4 days; open, 5 days; P = 0.063). Estimated blood loss per case
      with ECS and subsequent laparoscopy was significantly lower than in the open
      cases (63 vs. 147 cc; P = 0.0017). In both groups, wound complications occurred
      in five patients (laparoscopic, 20 %; open, 29 %; P = 0.71). There was one
      midline hernia recurrence and two lateral abdominal wall hernia occurrences post
      operatively in the laparoscopic group, whereas there were no midline and one
      lateral wall hernia occurrence in the open group. CONCLUSIONS: Patients
      undergoing endoscopic component separation with subsequent laparoscopic fascial
      reapproximation had a significantly shorter operative time and estimated blood
      loss when compared with open fascial reapproximation. Wound complications were
      similar in both groups although there were a greater number of hernia occurrences
      post-operatively in the laparoscopic group, though of no statistical
      significance.

PMID- 24912736
TI  - An 8-week stress management program in pathological gamblers: a pilot randomized
      controlled trial.
AB  - Stress plays a major role at the onset and relapse of pathological gambling (PG),
      but at the same time it can also be the aftermath of gambling behavior, thus
      revealing a reciprocal relationship. Although the role of stress has been well
      documented, there is a paucity of studies investigating the effect of an
      adjunctive stress management program on PG. In this 8-week parallel randomized
      waitlist controlled trial pathological gamblers, already in the gamblers
      anonymous (GA) group, were assigned randomly in two groups, with the intervention
      group (n = 22) receiving an additional stress management program (consisting of
      education on diet and exercise, stress coping methods, relaxation breathing -RB-
      and progressive muscle relaxation -PMR). Self-reported measures were used in
      order to evaluate stress, depression, anxiety, sleep quality/disturbances, life
      satisfaction and daily routine. The statistical analyses for the between group
      differences concerning the main psychosocial study outcomes revealed a
      statistically significant amelioration of stress, depression, anxiety symptoms
      and an increase of life-satisfaction and a better daily routine in participants
      of the intervention group. We hope that these will encourage researchers and
      clinicians to adopt stress management in their future work. 

PMID- 24912735
TI  - LSD1 promotes oxidative metabolism of white adipose tissue.
AB  - Exposure to environmental cues such as cold or nutritional imbalance requires
      white adipose tissue (WAT) to adapt its metabolism to ensure survival. Metabolic
      plasticity is prominently exemplified by the enhancement of mitochondrial
      biogenesis in WAT in response to cold exposure or beta3-adrenergic stimulation.
      Here we show that these stimuli increase the levels of lysine-specific
      demethylase 1 (LSD1) in WAT of mice and that elevated LSD1 levels induce
      mitochondrial activity. Genome-wide binding and transcriptome analyses
      demonstrate that LSD1 directly stimulates the expression of genes involved in
      oxidative phosphorylation (OXPHOS) in cooperation with nuclear respiratory factor
      1 (Nrf1). In transgenic (Tg) mice, increased levels of LSD1 promote in a cell
      autonomous manner the formation of islets of metabolically active brown-like
      adipocytes in WAT. Notably, Tg mice show limited weight gain when fed a high-fat
      diet. Taken together, our data establish LSD1 as a key regulator of OXPHOS and
      metabolic adaptation in WAT. 

PMID- 24912737
TI  - Social attribution skills of children born preterm at very low birth weight.
AB  - Children born prematurely at very low birth weight (<1500 g) are at increased
      risk for impairments affecting social functioning, including autism spectrum
      disorders (e.g., Johnson et al., 2010). In the current study, we used the Happe
      Frith animated triangles task (Abell, Happe, & Frith, 2000) to study social
      attribution skills in this population. In this task, typical viewers attribute
      intentionality and mental states to shapes, based on characteristics of their
      movements. Participants included 34 preterm children and 36 full-term controls,
      aged 8-11 years. Groups were comparable in terms of age at test, gender,
      handedness, and socioeconomic status; they also performed similarly on tests of
      selective attention/processing speed and verbal intelligence. Relative to full
      term peers, preterm children's descriptions of the animations were less
      appropriate overall; they also overattributed intentionality/mental states to
      randomly moving shapes and underattributed intentionality/mental states to shapes
      that seemed to be interacting socially. Impairments in the ability to infer the
      putative mental states of triangles from movement cues alone were most evident in
      children displaying more "autistic-like" traits, and this may reflect atypical
      development of and/or functioning in, or atypical connections between, parts of
      the social brain. 

PMID- 24912739
TI  - Nurses assessing pain with the Nociception Coma Scale: interrater reliability and
      validity.
AB  - The Nociception Coma Scale (NCS) is a pain observation tool, developed for
      patients with disorders of consciousness (DOC) due to acquired brain injury
      (ABI). The aim of this study was to assess the interrater reliability of the NCS
      and NCS-R among nurses for the assessment of pain in ABI patients with DOC. A
      secondary aim was further validation of both scales by assessing its
      discriminating abilities for the presence or absence of pain. Hospitalized
      patients with ABI (n = 10) were recorded on film during three conditions:
      baseline, after tactile stimulation, and after noxious stimulation. All
      stimulations were part of daily treatment for these patients. The 30 recordings
      were assessed with the NCS and NCS-R by 27 nurses from three university hospitals
      in the Netherlands. Each nurse viewed 9 to 12 recordings, totaling 270
      assessments. Interrater reliability of the NCS/NCS-R items and total scores were
      estimated by intraclass correlations (ICC), which showed excellent and equal
      average measures reliability for the NCS and NCR-R total scores (ICC 0.95), and
      item scores (range 0.87-0.95). Secondary analysis was performed to assess
      differences in ICCs among nurses' education and experience and to assess the
      scales discriminating properties for the presence of pain. The NCS and NCS-R are
      valid and reproducible scales that can be used by nurses with an associate (of
      science) in nursing degree or baccalaureate (of science) in nursing degree. It
      seems that more experience with ABI patients is not a predictor for good
      agreement in the assessment of the NCS(-R). 

PMID- 24912738
TI  - De novo assembly of red clover transcriptome based on RNA-Seq data provides
      insight into drought response, gene discovery and marker identification.
AB  - BACKGROUND: Red clover (Trifolium pratense L.) is a versatile forage crop legume,
      which can tolerate a variety of soils and is suitable for silage production for
      winter feed and for grazing. It is one of the most important forage legumes in
      temperate livestock agriculture. Its beneficial attributes include ability to fix
      nitrogen, improve soil and provide protein rich animal feed. It is however, a
      short-lived perennial providing good biomass yield for two or three years.
      Improved persistency is thus a major breeding target. Better water-stress
      tolerance is one of the key factors influencing persistency, but little is known
      about how red clover tolerates water stress. RESULTS: Plants from a full sib
      mapping family were used in a drought experiment, in which the growth rate and
      relative water content (RWC) identified two pools of ten plants contrasting in
      their tolerance to drought. Key metabolites were measured and RNA-Seq analysis
      was carried out on four bulked samples: the two pools sampled before and after
      drought. Massively parallel sequencing was used to analyse the bulked RNA
      samples. A de novo transcriptome reconstruction based on the RNA-Seq data was
      made, resulting in 45181 contigs, representing 'transcript tags'. These
      transcript tags were annotated with gene ontology (GO) terms. One of the most
      striking results from the expression analysis was that the drought sensitive
      plants were characterised by having approximately twice the number of
      differentially expressed transcript tags than the tolerant plants after drought.
      This difference was evident in most of the major GO terms. Before onset of
      drought the sensitive plants overexpressed a number of genes annotated as
      senescence-related. Furthermore, the concentration of three metabolites,
      particularly pinitol, but also proline and malate increased in leaves after
      drought stress. CONCLUSIONS: This de novo assembly of a red clover transcriptome
      from leaf material of droughted and non-droughted plants provides a rich source
      for gene identification, single nucleotide polymorphisms (SNP) and short sequence
      repeats (SSR). Comparison of gene expression levels between pools and treatments
      identified candidate genes for further analysis of the genetic basis of drought
      tolerance in red clover.

PMID- 24912740
TI  - Effectiveness of external cold and vibration for procedural pain relief during
      peripheral intravenous cannulation in pediatric patients.
AB  - The aim of this study was to investigate the effect of external cold and
      vibration stimulation via Buzzy on the pain and anxiety level of children during
      peripheral intravenous (IV) cannulation. This study was a prospective, randomized
      controlled trial. The sample consisted of 176 children ages 7 to 12 years who
      were randomly assigned to two groups: a control group that received no peripheral
      IV cannulation intervention and an experimental group that received external cold
      and vibration via Buzzy. The same nurse conducted the peripheral IV cannulation
      in all the children, and the same researcher applied the external cold and
      vibration to all the children. The external cold and the vibration were applied 1
      minute before the peripheral IV cannulation procedure and continued until the end
      of the procedure. Preprocedural anxiety was assessed using the Children's Fear
      Scale, along with reports by the children, their parents, and an observer.
      Procedural anxiety was assessed with the Children's Fear Scale and the parents'
      and the observer's reports. Procedural pain was assessed using the Wong Baker
      Faces Scale and the visual analog scale self-reports of the children.
      Preprocedural anxiety did not differ significantly. Comparison of the two groups
      showed significantly lower pain and anxiety levels in the experimental group than
      in the control group during the peripheral IV cannulation. Buzzy can be
      considered to provide an effective combination of coldness and vibration. This
      method can be used during pediatric peripheral IV cannulation by pediatric
      nurses.

PMID- 24912741
TI  - Impact of the Geriatric Medication Game(r) on nursing students' empathy and
      attitudes toward older adults.
AB  - BACKGROUND: Nurses should be well-prepared to improve and address health-related
      needs of older adults, but students may have difficulty understanding and
      empathizing, as they may not yet have personally experienced aging-related
      challenges. Simulation games can be used to help students understand the
      experiences of others, but limited information is available on the impact of
      simulation experiences on student empathy. OBJECTIVE: The objective of this study
      was to examine the impact of participation in an aging simulation game on nursing
      students' empathy and attitudes toward older adults as well as their
      understanding of patients' experiences in the healthcare system. DESIGN: This
      study used a quasi-experimental, pretest-posttest design. SETTING: A school of
      nursing in the Midwestern United States. PARTICIPANTS: The convenience sample
      included 58 sophomore-level baccalaureate nursing students. METHODS: Students
      played the role of an older adult during a 3-hour laboratory aging simulation
      game, the Geriatric Medication Game(r) (GMG). Students completed the (1) Kiersma
      Chen Empathy Scale (KCES, 15 items, 7-point Likert-type), (2) Jefferson Scale of
      Empathy-Health Professions Students (JSE-HPS, 20 items, 7-point Likert-type), and
      (3) Aging Simulation Experience Survey (13 items, 7-point Likert-type) pre- and
      post-game to assess study objectives. Descriptive statistics and paired t-tests
      were performed in SPSS v.21.0, as the data were normally distributed. RESULTS:
      Students' empathy (N=58) toward older adults significantly improved overall (KCES
      p=0.015, JSE-HPS p<0.001). Improvements also were seen on seven out of 13
      questions related to attitudes and healthcare understanding (p<0.05). In the post
      test, students agreed that they experienced frustration and impatience during the
      GMG. CONCLUSIONS: Students may not be aware of older adults' feelings and
      experiences prior to experiencing aging-related changes themselves. Simulation
      activities, such as the GMG, can be a useful mechanism for addressing empathy and
      caring during student education.

PMID- 24912742
TI  - The challenge of multimorbidity in nurse education: an international perspective.
AB  - The rise in prevalence of chronic diseases has become a global healthcare
      priority and a system wide approach has been called for to manage this growing
      epidemic. Whilst healthcare reform to tackle the scale of chronic disease and
      other long term conditions is still in its infancy, there is an emerging
      recognition that in an ageing society, people often suffer from more than one
      chronic disease at the same time. Multimorbidity poses new and distinct
      challenges and was the focus of a global conference held by the Organization of
      Economic Cooperation and Development (OECD) in 2011. Health education was raised
      as requiring radical redesign to equip graduates with the appropriate skills to
      face the challenges ahead. We wanted to explore how different aspects of
      multimorbidity were addressed within pre-registration nurse education and held an
      international (United Kingdom-Sweden) nurse workshop in Linkoping, Sweden in
      April 2013, which included nurse academics and clinicians. We also sent
      questionnaire surveys to final year student nurses from both countries. This
      paper explores the issues of multimorbidity from a patient, healthcare and nurse
      education perspective and presents the preliminary discussions from the workshop
      and students' survey. 

PMID- 24912743
TI  - Septocutaneous tensor fasciae latae perforator flap for breast reconstruction:
      radiological considerations and clinical cases.
AB  - INTRODUCTION: The deep inferior epigastric artery perforator (DIEP) flap is the
      first choice in autologous breast reconstruction; in cases when it cannot be
      used, alternative flaps are available. A radiological study and clinical cases
      using septocutaneous tensor fasciae latae (sc-TFL) flap for breast reconstruction
      are presented. MATERIALS: Magnetic resonance angiographies (MRAs) of 55 patients
      were evaluated. The pedicle and the perforators of the TFL were studied. Five
      consecutive sc-TFL flaps for breast reconstruction were performed. RESULTS:
      Thirty-seven MRA scans were included. There was a mean of 1.5 septocutaneous
      perforators per thigh. The mean pedicle length was 8.3 cm. Every perforator
      originated from a branch of the lateral circumflex femoral artery (LCFA). The
      LCFA originated from the arteria femoralis profunda in 89.2% of cases. In the
      vertical plane, the mean distance of the perforator from the antero-superior
      iliac spine was 8.7 cm. There were no major complications in the five sc-TFL
      performed. CONCLUSION: On MRA, the septocutaneous pedicle of the TFL perforator
      flap was consistently present. MR angiographic assessment of the septocutaneous
      branches was very helpful in the preoperative evaluation of our patients.
      Dissection of the sc-TFL can be performed in a supine position simultaneously
      with mastectomy and/or dissection of the mammary vessels. Finally, the donor-site
      scar can be hidden by underwear, giving minimal deformity. We recommend the sc
      TFL flap as a good alternative to the DIEP flap for autologous breast
      reconstruction. Preoperative imaging is mandatory for correct planning of the
      flap.

PMID- 24912744
TI  - Reference to locations in medical nomenclature.

PMID- 24912745
TI  - Performance of Gram and Acridine-orange staining in hand phlegmon.

PMID- 24912746
TI  - Resident physicians' attitudes and confidence in communicating with patients: a
      pilot study at a Japanese university hospital.
AB  - OBJECTIVE: This study aimed to explore the relationships among physicians'
      confidence in conducting medical interviews, their attitudes toward the patient
      physician relationship, and undergraduate training in communication skills among
      resident physicians in Japan. METHODS: Participants were 63 first-year resident
      physicians at a university hospital in Tokyo. The Physician Confidence in the
      Medical Interview scale (PCMI) was constructed based on the framework of the
      Calgary-Cambridge Guide. Additionally, participants' attitudes toward the patient
      physician relationship (Patient-Practitioner Orientation Scale; PPOS),
      undergraduate experience of communication skills training, and demographic
      characteristics were assessed through a self-reported questionnaire. RESULTS: The
      internal consistency of the PCMI and PPOS scales were adequate. As expected from
      the undergraduate curriculum for medical interviews in Japan, residents had
      relatively higher confidence in their communication skills with respect to
      gathering information and building the relationship, whereas less confident about
      sharing information and planning treatment. The PCMI was associated with a more
      patient-centered attitude as measured by the PPOS. CONCLUSION: These scales could
      be useful tools to measure physicians' confidence and attitudes in communicating
      with patients and to explore their changes through medical education. PRACTICE
      IMPLICATIONS: Residency programs should consider including systematic training
      and assessment in communication skills related to sharing information and
      planning treatment.

PMID- 24912747
TI  - Zoledronic acid causes gammadelta T cells to target monocytes and down-modulate
      inflammatory homing.
AB  - Zoledronic acid (ZA) is a potential immunotherapy for cancer because it can
      induce potent gammadelta T-cell-mediated anti-tumour responses. Clinical trials
      are testing the efficacy of intravenous ZA in cancer patients; however, the
      effects of systemic ZA on the activation and migration of peripheral gammadelta T
      cells remain poorly understood. We found that gammadelta T cells within ZA
      treated peripheral blood mononuclear cells were degranulating, as shown by up
      regulated expression of CD107a/b. Degranulation was monocyte dependent because
      CD107a/b expression was markedly reduced in the absence of CD14(+) cells.
      Consistent with monocyte-induced degranulation, we observed gammadelta T-cell
      dependent induction of monocyte apoptosis, as shown by phosphatidylserine
      expression on monocytes and decreased percentages of monocytes in culture.
      Despite the prevailing paradigm that ZA promotes tumour homing in gammadelta T
      cells, we observed down-modulation of their tumour homing capacity, as shown by
      decreased expression of the inflammatory chemokine receptors CCR5 and CXCR3, and
      reduced migration towards the inflammatory chemokine CCL5. Taken together our
      data suggest that ZA causes gammadelta T cells to target monocytes and down
      modulate the migratory programme required for inflammatory homing. This study
      provides novel insight into how gammadelta T cells interact with monocytes and
      the possible implications of systemic use of ZA in cancer. 

PMID- 24912748
TI  - Symplocos cochinchinensis attenuates streptozotocin-diabetes induced
      pathophysiological alterations of liver, kidney, pancreas and eye lens in rats.
AB  - The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE)
      has been explored against hyperglycemia associated secondary complications in
      streptozotocin induced diabetic rat model. The experimental groups consist of
      normal control (NC), diabetic control (DC), DC + metformin 100 mg kg(-1) bwd, DC
      + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21
      days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, %
      HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase,
      albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the
      eye lens was also checked. On day 21, DC rats showed significantly abnormal
      glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and
      GSH, elevated AR activity, hepatic and renal oxidative stress markers like
      malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited
      increased level of plasma urea and creatinine. Treatment with SCE protected from
      the deleterious alterations of biochemical parameters in a dose dependent manner
      including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of
      glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR
      activity (15.99%), and hepatic, renal oxidative stress and function markers
      compared to DC group. Considerable amount of liver and muscle glycogen was
      replenished by SCE treatment in diabetic animals. Although metformin showed
      better effect, the activity of SCE was very much comparable with this drug.

PMID- 24912749
TI  - Involvement of neutrophil gelatinase-associated lipocalin and osteopontin in
      renal tubular regeneration and interstitial fibrosis after cisplatin-induced
      renal failure.
AB  - The kidney has a capacity to recover from ischemic or toxic insults that result
      in cell death, and timely tissue repair of affected renal tubules may arrest
      progression of injury, leading to regression of injury and paving the way for
      recovery. To investigate the roles of neutrophil gelatinase-associated lipocalin
      (NGAL/lcn2) and osteopontin (OPN/spp1) during renal regeneration, the expression
      patterns of NGAL and OPN in the cisplatin-induced rat renal failure model were
      examined. NGAL expression was increased from day 1 after injection; it was seen
      mainly in the completely regenerating proximal tubules of the cortico-medullary
      junction on days 3-35; however, the expression was not seen in abnormally dilated
      or atrophied renal tubules surrounded by fibrotic lesions. On the other hand, OPN
      expression was increased from day 5 and the increased expression developed
      exclusively in the abnormal renal tubules. NGAL expression level well correlated
      with the proliferating activity in the regenerating renal epithelial cells,
      whereas OPN significantly correlated with the alpha-smooth muscle actin-positive
      myofibroblast appearance, expression of transforming growth factor (TGF)-beta1,
      and the number of CD68-positive macrophages. Interestingly, rat renal epithelial
      cell line (NRK-52E) treated with TGF-beta1 decreased NGAL expression, but
      increased OPN expression in a dose-dependent manner. Because increases of TGF
      beta1, myofibroblasts and macrophages contribute to progressive interstitial
      renal fibrosis, OPN may be involved in the pathogenesis of fibrosis; on the
      contrary, NGAL may play a role in tubular regeneration after injury. Expression
      analysis of NGAL and OPN would be useful to investigate the tubule damage in
      renal-toxicity.

PMID- 24912750
TI  - The role of novel anticoagulants in the management of venous thromboembolic
      disease.
AB  - OPINION STATEMENT: The introduction of oral direct coagulation factor inhibitors
      is dramatically changing the landscape of anticoagulation delivery in patients
      experiencing or at risk for a thrombotic event. These novel anticoagulants can be
      particularly attractive for health care providers, as they deliver therapeutic
      anticoagulation at a fixed dose, require no routine coagulation monitoring, and
      have few drug interactions and no food restrictions. Herein, we will review the
      role of these novel anticoagulants for acute venous thromboembolism treatment,
      primary and secondary venous thromboembolism prevention, and management during
      the periprocedural period.

PMID- 24912751
TI  - Role of main neuroendocrine pathways activated by swim stress on mast cell
      dependent peritoneal TNF production after LPS administration in mice.
AB  - OBJECTIVE AND DESIGN: To characterize the effects of swim stress on the early
      mast cell (MC)-dependent peritoneal production of TNF in response to
      lipopolysaccharide (LPS) administration in mice, identifying the neuroendocrine
      mediators involved. SUBJECTS: Ten to twelve-week-old Swiss Webster, C57BL/6 J or
      c-Kit (Wsh/Wsh) mice were used. TREATMENT: Animals were intraperitoneally
      challenged with LPS at different times after forced swimming (FS) and peak TNF
      production was determined in peritoneal washes at optimal time after LPS
      administration. Selective blockage of main neuroendocrine pathways was performed
      before swim stress. METHODS: TNF concentrations were determined by ELISA.
      RESULTS: FS provoked an immediate and transient inhibition of LPS-elicited, MC
      dependent TNF accumulation in peritoneum, which lasted around 30 min. Suppresive
      effects of FS were absent on MC-deficient c-Kit (Wsh/Wsh) mice but were recovered
      after reconstitution with MC. Adrenalectomy or DSP4 administration increased
      basal ip TNF levels and enhanced LPS-induced TNF release without any effect on
      stress-induced inhibitory effects, mifepristone did not produce any change on
      stress-induced inhibition, whereas mecamylamine administration increased basals
      and attenuated stress effects. CONCLUSIONS: Swim stress transiently inhibits the
      canonical MC-dependent response of TNF production in response to LPS in murine
      peritoneal cavity with the main participation of the cholinergic anti
      inflammatory reflex.

PMID- 24912752
TI  - Full-field digital mammography image data storage reduction using a crop tool.
AB  - PURPOSE: The storage requirements for full-field digital mammography (FFDM) in a
      picture archiving and communication system are significant, so methods to reduce
      the data set size are needed. A FFDM crop tool for this purpose was designed,
      implemented, and tested. MATERIALS AND METHODS: A total of 1,651 screening
      mammography cases with bilateral FFDMs were included in this study. The images
      were cropped using a DICOM editor while maintaining image quality. The cases were
      evaluated according to the breast volume (1/4, 2/4, 3/4, and 4/4) in the
      craniocaudal view. The image sizes between the cropped image group and the
      uncropped image group were compared. The overall image quality and reader's
      preference were independently evaluated by the consensus of two radiologists.
      RESULTS: Digital storage requirements for sets of four uncropped to cropped FFDM
      images were reduced by 3.8 to 82.9 %. The mean reduction rates according to the
      1/4-4/4 breast volumes were 74.7, 61.1, 38, and 24 %, indicating that the lower
      the breast volume, the smaller the size of the cropped data set. The total image
      data set size was reduced from 87 to 36.7 GB, or a 57.7 % reduction. The overall
      image quality and the reader's preference for the cropped images were higher than
      those of the uncropped images. CONCLUSION: FFDM mammography data storage
      requirements can be significantly reduced using a crop tool.

PMID- 24912753
TI  - Creation of catalytically active particles from enzymes crosslinked with a
      natural bifunctional agent--homocysteine thiolactone.
AB  - The current study describes an approach to creation of catalytically active
      particles with increased stability from enzymes by N-homocysteinylation, a
      naturally presented protein modification. Enzymatic activities and properties of
      two globular tetrameric enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      and lactate dehydrogenase (LDH) were studied before and after N
      homocysteinylation. Modification of these proteins concerns the accessible lysine
      residues and introduces an average of 2-2,5 homocysteine residues per protein
      monomer. Formation of a range of aggregates was observed for both enzymes, which
      assemble via formation of intermolecular noncovalent bonds and by disulfide
      bonds. It was demonstrated that both studied enzymes retain their catalytic
      activities on modification and the subsequent formation of oligomeric forms. At
      low concentrations of homocysteine thiolactone, modification of GAPDH leads not
      only to prevention of spontaneous inactivation but also increases thermal
      stability of this enzyme on heating to 80 degrees C. A moderate reduction of the
      activity of GAPDH observed in case of its crosslinking with 50-fold excess of
      homocysteine thiolactone per lysine is probably caused by hindered substrate
      diffusion. Spherical particles of 100 nm and larger diameters were observed by
      transmission electron microscopy and atomic force microscope techniques after
      modification of GAPDH with different homocysteine thiolactone concentrations. In
      case of LDH, branched fibril-like aggregates were observed under the same
      conditions. Interestingly, crosslinked samples of both proteins were found to
      have reversible thermal denaturation profiles, indicating that modification with
      homocysteine thiolactone stabilizes the spatial structure of these enzymes.

PMID- 24912754
TI  - Anti-ribosomal P protein antibody and prognosis in autoimmune hepatitis.

PMID- 24912755
TI  - Triadic motifs in the dependence networks of virtual societies.
AB  - In friendship networks, individuals have different numbers of friends, and the
      closeness or intimacy between an individual and her friends is heterogeneous.
      Using a statistical filtering method to identify relationships about who depends
      on whom, we construct dependence networks (which are directed) from weighted
      friendship networks of avatars in more than two hundred virtual societies of a
      massively multiplayer online role-playing game (MMORPG). We investigate the
      evolution of triadic motifs in dependence networks. Several metrics show that the
      virtual societies evolved through a transient stage in the first two to three
      weeks and reached a relatively stable stage. We find that the unidirectional loop
      motif (M9) is underrepresented and does not appear, open motifs are also
      underrepresented, while other close motifs are overrepresented. We also find
      that, for most motifs, the overall level difference of the three avatars in the
      same motif is significantly lower than average, whereas the sum of ranks is only
      slightly larger than average. Our findings show that avatars' social status plays
      an important role in the formation of triadic motifs. 

PMID- 24912756
TI  - Bemisia tabaci Q carrying tomato yellow leaf curl virus strongly suppresses host
      plant defenses.
AB  - The concurrence of tomato yellow leaf curl virus (TYLCV) with the spread of its
      vector Bemisia tabaci Q rather than B in China suggests a more mutualistic
      relationship between TYLCV and Q. Here, we investigated the hypothesis that
      viruliferous B and Q have different effects on plant defenses. We found the
      fecundity of nonviruliferous B, nonviruliferous Q, viruliferous Q and
      viruliferous B was 11.080, 12.060, 10.760, and 11.220 respectively on plants
      previously attacked by the other biotype, however, on their respective
      noninfested control leaves fecundity was 12.000, 10.880, 9.760, and 8.020
      respectively. Only viruliferous B had higher fecundity on viruliferous Q-infested
      plants than on control plants. The longevity of viruliferous B showed the same
      phenomenon. At 1 d infestion, the jasmonic acid content in leaves noninfested and
      in leaves infested with nonviruliferous B, nonviruliferous Q, viruliferous B and
      viruliferous Q was 407.000, 281.333, 301.333, 266.667 and 134.000 ng/g FW,
      respectively. The JA content was lowest in viruliferous Q-infested leaves. The
      proteinase inhibitor activity and expression of JA-related upstream gene LOX and
      downstream gene PI II showed the same trend. The substantial suppression of host
      defenses by Q carrying TYLCV probably enhances the spread of Q and TYLCV in
      China. 

PMID- 24912758
TI  - Exposure of hairdressers to ortho- and meta-toluidine in hair dyes.
AB  - BACKGROUND: Carcinogenic aromatic amines derived from hair dyes have recently
      received new attention. One of these is ortho (o)-toluidine, which is classified
      as carcinogenic to humans. OBJECTIVES: To clarify exposure of hairdressers to
      potentially carcinogenic aromatic amines, including o-toluidine. METHODS: We
      measured eight potentially carcinogenic aromatic amines in the blood of 295
      hairdressers, 32 users of hair dyes and 60 controls. The study was restricted to
      female non-smokers. Lifestyle data were collected for all participants using self
      administered questionnaires. Blood samples were taken for analysis of ortho-,
      meta (m)- and para (p)-toluidine; 2-, 3- and 4-ethylaniline, 2,3- and 3,4
      dimethylaniline as haemoglobin adducts. The samples were analysed with gas
      chromatography-tandem mass spectrometry. RESULTS: Generally, adduct
      concentrations were in the range of 0-200 pg/g haemoglobin. A comparison of the
      adduct concentrations found in hairdressers, consumers and controls showed no
      statistically significant differences. However, for hairdressers, o- and m
      toluidine concentrations increased significantly with the weekly number of hair
      waving (p=0.020) and permanent hair dyeing treatments (p=0.026), respectively. o
      Toluidine and m-Toluidine concentrations also tended (p=0.076 and 0.080,
      respectively) to increase with the frequency of light-colour permanent hair dye
      treatments. CONCLUSIONS: Hairdressers who use light-colour permanent hair dyes,
      other permanent hair dyes and hair waving treatments seem to be exposed to o- and
      m-toluidine as indicated by associations with the number of treatments performed.
      Analyses of hair waving and hair dye products should be performed to identify the
      possible sources of exposure to o- and m-toluidine.

PMID- 24912760
TI  - Association of serum omentin-1 concentrations with the presence and severity of
      preeclampsia.
AB  - BACKGROUND: Inflammation is involved in the pathogenesis of preeclampsia. Omentin
      is a newly discovered adipokine that possesses an anti-inflammatory function. The
      aim of this study was to determine the association of serum omentin-1
      concentration with the presence and severity of preeclampsia. METHODS: Serum
      concentrations of omentin-1 were measured in 128 women with preeclampsia and 96
      women with uncomplicated pregnancies using an enzyme-linked immunosorbent assay
      method. RESULTS: Patients with preeclampsia had significantly lower serum
      concentrations of omentin-1 compared to healthy controls. In addition, those
      patients with severe preeclampsia had significantly lower concentrations of serum
      omentin-1 compared to those with mild preeclampsia. Simple linear regression
      analysis showed that in patients with preeclampsia the serum concentrations of
      omentin-1 showed significant correlation with body mass index (P < 0.001),
      systolic blood pressure (P < 0.05) and homeostasis model assessment of insulin
      resistance (P < 0.001). CONCLUSION: Decreased concentrations of serum omentin-1
      appear to be associated with the presence and severity of preeclampsia.

PMID- 24912759
TI  - Up-regulated HMGB1 in EAM directly led to collagen deposition by a PKCbeta/Erk1/2
      dependent pathway: cardiac fibroblast/myofibroblast might be another source of
      HMGB1.
AB  - High mobility group box 1 (HMGB1), an important inflammatory mediator, is
      actively secreted by immune cells and some non-immune cells or passively released
      by necrotic cells. HMGB1 has been implicated in many inflammatory diseases. Our
      previous published data demonstrated that HMGB1 was up-regulated in heart tissue
      or serum in experimental autoimmune myocarditis (EAM); HMGB1 blockade could
      ameliorate cardiac fibrosis at the last stage of EAM. And yet, until now, no data
      directly showed that HMGB1 was associated with cardiac fibrosis. Therefore, the
      aims of the present work were to assess whether (1) up-regulated HMGB1 could
      directly lead to cardiac fibrosis in EAM; (2) cardiac fibroblast/myofibroblasts
      could secrete HMGB1 as another source of high-level HMGB1 in EAM; and (3) HMGB1
      blockade could effectively prevent cardiac fibrosis at the last stage of EAM. Our
      results clearly demonstrated that HMGB1 could directly lead to cardiac collagen
      deposition, which was associated with PKCbeta/Erk1/2 signalling pathway;
      furthermore, cardiac fibroblast/myofibroblasts could actively secrete HMGB1 under
      external stress; and HMGB1 secreted by cardiac fibroblasts/myofibroblasts led to
      cardiac fibrosis via PKCbeta activation by autocrine means; HMGB1 blockade could
      efficiently ameliorate cardiac fibrosis in EAM mice. 

PMID- 24912761
TI  - Russian normative data for 375 action pictures and verbs.
AB  - The present article introduces a Russian-language database of 375 action pictures
      and associated verbs with normative data. The pictures were normed for name
      agreement, conceptual familiarity, and subjective visual complexity, and measures
      of age of acquisition, imageability, and image agreement were collected for the
      verbs. Values of objective visual complexity, as well as information about verb
      frequency, length, argument structure, instrumentality, and name relation, are
      also provided. Correlations between these parameters are presented, along with a
      comparative analysis of the Russian name agreement norms and those collected in
      other languages. The full set of pictorial stimuli and the obtained norms may be
      freely downloaded from http://neuroling.ru/en/db.htm for use in research and for
      clinical purposes. 

PMID- 24912762
TI  - Visual DMDX: A web-based authoring tool for DMDX, a Windows display program with
      millisecond accuracy.
AB  - DMDX is a software package for the experimental control and timing of stimulus
      display for Microsoft Windows systems. DMDX is reliable, flexible, millisecond
      accurate, and can be downloaded free of charge; therefore it has become very
      popular among experimental researchers. However, setting up a DMDX-based
      experiment is burdensome because of its command-based interface. Further, DMDX
      relies on RTF files in which parts of the stimuli, design, and procedure of an
      experiment are defined in a complicated (DMASTR-compatible) syntax. Other
      experiment software, such as E-Prime, Psychopy, and WEXTOR, became successful as
      a result of integrated visual authoring tools. Such an intuitive interface was
      lacking for DMDX. We therefore created and present here Visual DMDX
      (http://visualdmdx.com/), a HTML5-based web interface to set up experiments and
      export them to DMDX item files format in RTF. Visual DMDX offers most of the
      features available from the rich DMDX/DMASTR syntax, and it is a useful tool to
      support researchers who are new to DMDX. Both old and modern versions of DMDX
      syntax are supported. Further, with Visual DMDX, we go beyond DMDX by having
      added export to JSON (a versatile web format), easy backup, and a preview option
      for experiments. In two examples, one experiment each on lexical decision making
      and affective priming, we explain in a step-by-step fashion how to create
      experiments using Visual DMDX. We release Visual DMDX under an open-source
      license to foster collaboration in its continuous improvement.

PMID- 24912763
TI  - Reduction of respiratory motion artifacts for free-breathing whole-heart coronary
      MRA by weighted iterative reconstruction.
AB  - PURPOSE: To combine weighted iterative reconstruction with self-navigated free
      breathing coronary magnetic resonance angiography for retrospective reduction of
      respiratory motion artifacts. METHODS: One-dimensional self-navigation was
      improved for robust respiratory motion detection and the consistency of the
      acquired data was estimated on the detected motion. Based on the data
      consistency, the data fidelity term of iterative reconstruction was weighted to
      reduce the effects of respiratory motion. In vivo experiments were performed in
      14 healthy volunteers and the resulting image quality of the proposed method was
      compared to a navigator-gated reference in terms of acquisition time, vessel
      length, and sharpness. RESULT: Although the sampling pattern of the proposed
      method contained 60% more samples with respect to the reference, the scan
      efficiency was improved from 39.5 +/- 10.1% to 55.1 +/- 9.1%. The improved self
      navigation showed a high correlation to the standard navigator signal and the
      described weighting efficiently reduced respiratory motion artifacts. Overall,
      the average image quality of the proposed method was comparable to the navigator
      gated reference. CONCLUSION: Self-navigated coronary magnetic resonance
      angiography was successfully combined with weighted iterative reconstruction to
      reduce the total acquisition time and efficiently suppress respiratory motion
      artifacts. The simplicity of the experimental setup and the promising image
      quality are encouraging toward future clinical evaluation.

PMID- 24912764
TI  - Facile synthesis of 3D Pd-P nanoparticle networks with enhanced electrocatalytic
      performance towards formic acid electrooxidation.
AB  - 3D Pd-P nanoparticle networks (NNs) have been successfully synthesized using a
      facile one-step soft-template-assisted method. The as-prepared Pd-P NNs exhibit
      markedly improved activity and stability towards formic acid electrooxidation
      over Pd NNs, commercial Pd/C and Pd-P nanoparticle aggregates (NAs). 

PMID- 24912765
TI  - Simulation of self expanding transcatheter aortic valve in a realistic aortic
      root: implications of deployment geometry on leaflet deformation.
AB  - Self expanding Transcatheter Aortic Valve Replacements (TAVR) can conform to the
      geometry of the aortic annulus and the calcified leaflet complex, which may
      result in leaflet distortion and altered leaflet kinematics, but such changes
      have not yet been characterized. In this study we developed a computational model
      to investigate the deployment of a self expanding TAVR in a realistic aortic root
      model derived from multi-slice computed tomography (MSCT) images. We simulated
      TAVR crimping/deployment in realistic and idealized aortic root models, followed
      by diastolic loading of the TAVR leaflets in its final deployed configuration.
      The TAVR deployed in a realistic aortic root had increased peak loading in the
      commissural region of the leaflets compared to TAVRs under idealized circular
      deployment conditions (2.97 vs. 1.52 MPa). Furthermore, orientation of the TAVR
      in the asymmetric aortic annulus such that the commissures of the TAVR are
      aligned with the native valve commissures minimized the effect of TAVR stent
      distortion on peak stresses in the TAVR leaflets (2.97 vs. 2.35 MPa). We propose
      that preoperative planning of the orientation of the TAVR in the aortic root
      annulus might minimize the impact of potential stent distortion on leaflet
      function and may in turn increase long term leaflet durability. 

PMID- 24912766
TI  - Passive stiffness of coupled wrist and forearm rotations.
AB  - Coordinated movement requires that the neuromuscular system account and
      compensate for movement dynamics. One particularly complex aspect of movement
      dynamics is the interaction that occurs between degrees of freedom (DOF), which
      may be caused by inertia, damping, and/or stiffness. During wrist rotations, the
      two DOF of the wrist (flexion-extension and radial-ulnar deviation, FE and RUD)
      are coupled through interaction torques arising from passive joint stiffness. One
      important unanswered question is whether the DOF of the forearm (pronation
      supination, PS) is coupled to the two DOF of the wrist. Answering this question,
      and understanding the dynamics of wrist and forearm rotations in general,
      requires knowledge of the stiffness encountered during rotations involving all
      three DOF (PS, FE, and RUD). Here we present the first-ever measurement of the
      passive stiffness encountered during simultaneous wrist and forearm rotations.
      Using a wrist and forearm robot, we measured coupled wrist and forearm stiffness
      in 10 subjects and present it as a 3-by-3 stiffness matrix. This measurement of
      passive wrist and forearm stiffness will enable future studies investigating the
      dynamics of wrist and forearm rotations, exposing the dynamics for which the
      neuromuscular system must plan and compensate during movements involving the
      wrist and forearm. 

PMID- 24912768
TI  - Thermodynamics for complex formation between palladium(ii) and oxalate.
AB  - Complex formation between [Pd(H2O)4](2+) and oxalate (ox = C2O4(2-)) has been
      studied spectrophoto-metrically in aqueous solution at variable temperature,
      ionic strength and pH. Thermodynamic parameters at 298.2 K and 1.00 mol dm(-3)
      HClO4 ionic medium for the complex formation [Pd(H2O)4](2+) + H2ox ?
      [Pd(H2O)2(ox)] + 2H3O(+) with equilibrium constant K1,H (in mol dm(-3)) are
      log10K1,H = 3.38 +/- 0.08, DeltaH = -33 +/- 3 kJ mol(-1), and DeltaS = -48 +/- 11
      J K(-1) mol(-1), as determined from spectrophotometric equilibrium titrations at
      15.0, 20.0, 25.0 and 31.0  degrees C. Thermodynamic overall stability constants
      beta (in (mol dm(-3))(-n), n = 1,2) for [Pd(H2O)2(ox)] and [Pd(ox)2](2-) at zero
      ionic strength and 298.2 K, defined as the equilibrium constants for the reaction
      Pd(2+) + nox(2-) ? [Pd(ox)n](2-2n) (water molecules omitted) are log10beta = 9.04
      +/- 0.06 and log10beta = 13.1 +/- 0.3, respectively, calculated by use of
      Specific Ion Interaction Theory from spectrophotometric titrations with initial
      hydrogen ion concentrations of 1.00, 0.100 and 0.0100 mol dm(-3) and ionic
      strengths of 1.00, 2.00 or 3.00 mol dm(-3). The values derived together with
      literature data give estimated overall stability constants for Pd(ii) compounds
      such as [Pd(en)(ox)] and cis-[Pd(NH3)2Cl2], some of them analogs to Pt(ii)
      complexes used in cancer treatment. The palladium oxalato complexes are
      significantly more stable than palladium(ii) complexes with monodentate O-bonding
      ligands. A comparison between several different palladium complexes shows that
      different parameters contribute to the stability variations observed. These are
      discussed together with the so-called chelate effect. 

PMID- 24912767
TI  - beta-adrenoceptor blockers valuable but higher doses not necessary.
AB  - beta-adrenoceptor blockers have an important role in the treatment of heart
      disease and are useful as an adjunct in systemic hypertension. They are often
      prescribed at unnecessarily high doses, near the top of the dose-response curve.
      Higher doses are associated with more adverse events, have not been shown to
      improve clinical outcomes in cardiac failure and may worsen outcome in
      hypertension. beta-adrenoceptor blockers can be very effective in lower doses,
      guided by close monitoring of heart rate and blood pressure and, when used in
      combination with low dose vasodilators and diuretics, give a better risk benefit
      profile. 

PMID- 24912769
TI  - Validity and reliability of balance assessment software using the Nintendo Wii
      balance board: usability and validation.
AB  - BACKGROUND: A balance test provides important information such as the standard to
      judge an individual's functional recovery or make the prediction of falls. The
      development of a tool for a balance test that is inexpensive and widely available
      is needed, especially in clinical settings. The Wii Balance Board (WBB) is
      designed to test balance, but there is little software used in balance tests, and
      there are few studies on reliability and validity. Thus, we developed a balance
      assessment software using the Nintendo Wii Balance Board, investigated its
      reliability and validity, and compared it with a laboratory-grade force platform.
      METHODS: Twenty healthy adults participated in our study. The participants
      participated in the test for inter-rater reliability, intra-rater reliability,
      and concurrent validity. The tests were performed with balance assessment
      software using the Nintendo Wii balance board and a laboratory-grade force
      platform. Data such as Center of Pressure (COP) path length and COP velocity were
      acquired from the assessment systems. The inter-rater reliability, the intra
      rater reliability, and concurrent validity were analyzed by an intraclass
      correlation coefficient (ICC) value and a standard error of measurement (SEM).
      RESULTS: The inter-rater reliability (ICC: 0.89-0.79, SEM in path length: 7.14
      1.90, SEM in velocity: 0.74-0.07), intra-rater reliability (ICC: 0.92-0.70, SEM
      in path length: 7.59-2.04, SEM in velocity: 0.80-0.07), and concurrent validity
      (ICC: 0.87-0.73, SEM in path length: 5.94-0.32, SEM in velocity: 0.62-0.08) were
      high in terms of COP path length and COP velocity. CONCLUSION: The balance
      assessment software incorporating the Nintendo Wii balance board was used in our
      study and was found to be a reliable assessment device. In clinical settings, the
      device can be remarkably inexpensive, portable, and convenient for the balance
      assessment.

PMID- 24912770
TI  - Automated reticulocyte parameters for hereditary spherocytosis screening.
AB  - The laboratory diagnosis of hereditary spherocytosis (HS) is based on several
      screening and confirmatory tests; our algorithm includes clinical features, red
      blood cell morphology analysis and cryohaemolysis test, and, in case of positive
      screening, sodium dodecyl sulphate polyacrylamide gel electrophoresis as a
      diagnostic test. Using the UniCel DxH800 (Beckman Coulter) haematology analyser,
      we investigated automated reticulocyte parameters as HS screening tool, i.e. mean
      reticulocyte volume (MRV), immature reticulocyte fraction (IRF) and mean sphered
      cell volume (MSCV). A total of 410 samples were screened. Gel electrophoresis was
      applied to 159 samples that were positive for the screening tests. A total of 48
      patients were diagnosed as HS, and seven were diagnosed as acquired autoimmune
      haemolytic anaemia (AIHA). Some other 31 anaemic conditions were also studied.
      From the receiver operating characteristic (ROC) curve analysis, both delta (mean
      cell volume (MCV)-MSCV) and MRV presented an area under the curve (AUC) of 0.98.
      At the diagnostic cut-off of 100 % sensitivity, MRV showed the best specificity
      of 88 % and a positive likelihood ratio of 8.7. The parameters IRF, MRV and MSCV
      discriminated HS not only from controls and other tested pathologies but also
      from AIHA contrary to the cryohaemolysis test. In conclusion, automated
      reticulocyte parameters might be helpful for haemolytic anaemia diagnostic
      orientation even for general laboratories. In combination with cryohaemolysis,
      they ensure an effective and time-saving screening for HS for more specialised
      laboratories.

PMID- 24912771
TI  - Negative prognostic value of CD34 antigen also if expressed on a small population
      of acute promyelocytic leukemia cells.
AB  - Potential clinical significance of CD34 expression in acute promyelocitic
      leukemia (APL) has not been deeply investigated. We hereby analyzed the clinico
      biological features and treatment outcome of APL patients in relation to CD34
      expression, even when expressed in a small subpopulation: 114 APL patients
      homogeneously treated with the AIDA schedule were included in the study and
      prognostic correlation with respect to CD34 expression, both when expressed in
      association with CD2 and as isolated expression (cutoff >=2 to <10 % or >=10 %),
      were investigated. CD34 was associated to CD2 in 30 patients and was isolated in
      19 patients. When compared to the CD34-negative population, CD34/CD2 expression
      identified a subgroup with characteristic features: M3 variant subtype (26 vs 7 %
      in the negative group, p = 0.02), bcr3 transcript subtype (73 vs 32 %, p =
      0.001), high risk according to the risk of relapse (66 vs 17 %, p = 0.002), high
      incidence of differentiation syndrome (26 vs 12 %, p = 0.01), lower overall
      survival (88 vs 95 %), and a significantly higher rate of relapse (22 vs 13.8 %,
      p = 0.05). We then evaluated the prognostic value of isolated CD34 expression: it
      was detected in nine patients with a cutoff of expression >=10 % and in 10
      patients with a cutoff >=2 but <10 %. Isolated CD34 positivity identified a
      subgroup with a classic morphology (79 %), bcr1 prevalence (53 %), higher rate of
      relapse (37 vs 13.8 % in the negative group, p = 0.002), higher incidence of
      differentiation syndrome (55 vs 12 %, p = 0.03), and lower overall survival (60
      vs 95 %, p = 0.001). The results of our study confirm that CD34/CD2 expression
      characterizes a subset of APL with a high WBC count and a variant morphological
      subtype, associated with an unfavorable clinical course. We also show that the
      isolated expression of CD34, even at a low cutoff, identifies a group of classic
      APL with a negative prognosis. Further studies aimed at identifying other
      molecular signatures in CD34-positive patients are needed in order to optimize
      the therapeutic strategy for this subset of patients.

PMID- 24912772
TI  - Toll-like receptor 2 and 9 genetic polymorphisms and the susceptibility to B cell
      Non-Hodgkin Lymphoma in Egypt.
AB  - Non-Hodgkin lymphomas (NHL) entail considerable heterogeneity regarding their
      morphology, clinical course, etiological factors, or response to therapy.
      Increased incidence of NHL in immunocompromised individuals and after autoimmune
      diseases suggests that infections and immune dysregulation could play a role in
      the susceptibility to NHL. Accordingly, genetic variation in Toll-like receptor
      (TLR) genes might be considered as molecular risk factors for NHL. The aim of the
      current study was to investigate the possible association between genetic
      polymorphism of the TLRs genes and B cell NHL (B-NHL) risk in Egypt. The present
      study included 100 B-NHL patients and 100 healthy controls. Genotyping of TLR2
      1350 T/C and TLR9-1237 T/C were done by polymerase chain reaction restricted
      fragment length polymorphism (PCR-RFLP) technique. The frequency of TLR2-1350 T/C
      polymorphic genotypes in B-NHL patients was 18 % for the heteromutant genotype
      (TC) and 1 % for the homomutant (CC). There was no statistical difference in the
      distribution of TLR2-1350 T/C genotypes between B-NHL patients and controls. As
      for TLR9-1237 T/C, the frequency of the heteromutant genotype (TC) was 58 % and
      the homomutant genotype (CC) was 1 % in B-NHL patients. Calculated risk
      estimation revealed that TLR9-1237 (TC) heterotype conferred almost fourfold
      increased risk of B-NHL (odds ratio (OR) = 3.93, 95 % confidence interval (CI) =
      2.16-7.14), and the risk was higher in patients with indolent subtypes (OR =
      6.64, 95 %CI = 2.31-9.08). In conclusion, the study revealed that TLR9-1237 T/C
      polymorphism can be considered as molecular risk factor for B-NHL among
      Egyptians.

PMID- 24912773
TI  - Structural basis of DDB1-and-Cullin 4-associated Factor 1 (DCAF1) recognition by
      merlin/NF2 and its implication in tumorigenesis by CD44-mediated inhibition of
      merlin suppression of DCAF1 function.
AB  - Merlin, a tumor suppressor encoded by the neurofibromatosis type 2 gene, has been
      shown to suppress tumorigenesis by inhibiting the Cullin 4-RING E3 ubiquitin
      ligase CRL4(DCAF) (1) in the nucleus. This inhibition is mediated by direct
      binding of merlin to DDB1-and-Cullin 4-associated Factor 1 (DCAF1), yet the
      binding mode of merlin to DCAF1 is not well defined. Here, we report structural
      and biophysical studies of the merlin binding to DCAF1 and its interference with
      CD44 binding. The crystal structure of the merlin FERM domain bound to the DCAF1
      C-terminal acidic tail reveals that the hydrophobic IILXLN motif located at the C
      terminal end of DCAF1 binds subdomain C of the FERM domain by forming a beta
      strand. The binding site and mode resemble that of merlin binding to the CD44
      cytoplasmic tail. Competition binding assay showed that CD44 and DCAF1 compete
      for binding to the merlin FERM domain in solution. The CD44 cytoplasmic tail is
      known to be cleaved for nuclear translocation by regulated intra-membrane
      proteolysis (RIP). Our structure implies that, in the nucleus, the CD44
      cytoplasmic tail cleaved by RIP could release DCAF1 from merlin by competing for
      binding to the merlin FERM domain, which results in the inhibition of merlin
      mediated suppression of tumorigenesis. 

PMID- 24912776
TI  - Modeling cancer glycolysis under hypoglycemia, and the role played by the
      differential expression of glycolytic isoforms.
AB  - The effect of hypoglycemia on the contents of glycolytic proteins, activities of
      enzymes/transporters and flux of HeLa and MCF-7 tumor cells was experimentally
      analyzed and modeled in silico. After 24 h hypoglycemia (2.5 mm initial glucose),
      significant increases in the protein levels of glucose transporters 1 and 3 (GLUT
      1 and 3) (3.4 and 2.1-fold, respectively) and hexokinase I (HKI) (2.3-fold) were
      observed compared to the hyperglycemic standard cell culture condition (25 mm
      initial glucose). However, these changes did not bring about a significant
      increase in the total activities (Vmax ) of GLUT and HK; instead, the affinity of
      these proteins for glucose increased, which may explain the twofold increased
      glycolytic flux under hypoglycemia. Thus, an increase in more catalytically
      efficient isoforms for two of the main controlling steps was sufficient to induce
      increased flux. Further, a previous kinetic model of tumor glycolysis was updated
      by including the ratios of GLUT and HK isoforms, modified pyruvate kinase
      kinetics and an oxidative phosphorylation reaction. The updated model was robust
      in terms of simulating most of the metabolite levels and fluxes of the cells
      exposed to various glycemic conditions. Model simulations indicated that the main
      controlling steps were glycogen degradation > HK > hexosephosphate isomerase
      under hyper- and normoglycemia, and GLUT > HK > glycogen degradation under
      hypoglycemia. These predictions were experimentally evaluated: the glycolytic
      flux of hypoglycemic cells was more sensitive to cytochalasin B (a GLUT
      inhibitor) than that of hyperglycemic cells. The results indicated that cancer
      glycolysis should be inhibited at multiple controlling sites, regardless of
      external glucose levels, to effectively block the pathway. DATABASE: The
      mathematical models described here have been submitted to the JWS Online Cellular
      Systems Modelling Database and can be accessed at
      http://jjj.mib.ac.uk/database/achcar/index.html. [Database section added 21 July
      2014 after original online publication].

PMID- 24912775
TI  - Variations in the most abundant types of glucosinolates found in the leaves of
      baby leaf rocket under typical commercial conditions.
AB  - BACKGROUND: Changes in the concentration of the three most abundant
      glucosinolates were measured in the leaves of perennial wall rocket [Diplotaxis
      tenuifolia (L.) DC.], and annual garden rocket (Eruca sativa Mill.). HPLC-MS was
      used to identify glucoraphanin, 4-hydroxyglucobrassin and glucoerucin from
      perennial wall rocket, and glucoraphanin, glucobrassicin and 4
      methoxyglucobrassicin from annual garden rocket. In separate experiments the
      responses of glucosinolates to harvest number, seasonal conditions, nitrogen
      supply and post-harvest storage conditions were measured. RESULTS: For perennial
      wall rocket, season influenced the concentration of glucoraphanin, which were
      highest for the spring [379 ug kg(-1) fresh weight (FW)] and summer (317 ug kg(
      1) FW) plantings. The concentration of 4-hydroxyglucobrassin was higher in the
      leaves of first harvest crops. This response was due to this glucosinolate not
      being detected in the leaves of second harvest crops. Thus, the parent
      glucosinolate was altered between the first and second harvests in response to
      the abiotic stresses caused by harvesting. For annual garden rocket, there was an
      interaction between the harvest number and season for all glucosinolates
      measured. However, no clear response was observed between these factors. Higher
      concentrations of glucobrassicin and 4-methoxyglucobrassicin were measured for
      first harvest leaves when compared to the second harvest. This was due to the
      absence of detection of these glucosinolates in the leaves of second harvested
      plants; consequently higher total glucosinolate concentrations were measured for
      the first harvest winter (1224 ug kg(-1) FW) and summer (864 ug kg(-1) FW) crops.
      CONCLUSION: The concentrations of individual glucosinolates vary greatly over
      typical pre- and post-harvest commercial conditions. The absence of 4
      hydroxyglucobrassin for perennial wall rocket, and glucobrassicin and 4
      methoxyglucobrassicin for annual garden rocket between harvests, illustrates that
      abiotic stress from harvesting has the capacity to alter the types of
      glucosinolates in leaves. Concentrations do not generally decline during a
      typical storage period, indicating that the potential benefits of these compounds
      are not lost during post-harvest storage.

PMID- 24912774
TI  - The effectiveness of nano chemotherapeutic particles combined with mifepristone
      depends on the PR isoform ratio in preclinical models of breast cancer.
AB  - There is clinical and experimental evidence suggesting that antiprogestins might
      be used for the treatment of selected breast cancer patients. Our aim was to
      evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated
      doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in
      experimental breast cancer models expressing different ratios of progesterone
      receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB)
      and two resistant (PRA<PRB) murine mammary carcinomas growing in BALB/c, GFP
      BALB/c or nude mice, along with human T47D-YA and T47D-YB xenografts growing in
      immunocompromised NSG mice. MFP improved the therapeutic effects of suboptimal
      doses of Nab-paclitaxel or PEG-LD in murine and human carcinomas with higher
      levels of PRA than PRB. MFP induced tissue remodeling in PRA-overexpressing
      tumors, increasing the stromal/tumor cell ratio and the number of functional
      vessels. Accordingly, an increase in nanoparticles and drug accumulation was
      observed in stromal and tumor cells in MFP-treated tumors. We conclude that MFP
      induces an increase in vessels during tissue remodeling, favoring the selective
      accumulation of nanoparticles inside the tumors. We propose that antiprogestins
      have the potential to enhance the efficacy of chemotherapy in breast tumors with
      a high PRA/PRB ratio. 

PMID- 24912777
TI  - A challenge of numbers and diversity: neurogenesis in the Drosophila optic lobe.
AB  - The brain areas that endow insects with the ability to see consist of remarkably
      complex neural circuits. Reiterated arrays of many diverse neuron subtypes are
      assembled into modular yet coherent functional retinotopic maps. Tremendous
      progress in developing genetic tools and cellular markers over the past years
      advanced our understanding of the mechanisms that control the stepwise production
      and differentiation of neurons in the visual system of Drosophila melanogaster.
      The postembryonic optic lobe utilizes at least two modes of neurogenesis that are
      distinct from other parts of the fly central nervous system. In the first optic
      ganglion, the lamina, neuroepithelial cells give rise to precursor cells, whose
      proliferation and differentiation depend on anterograde signals from
      photoreceptor axons. In the second optic ganglion, the medulla, the coordinated
      activity of four signaling pathways orchestrates the gradual conversion of
      neuroepithelial cells into neuroblasts, while a specific cascade of temporal
      identity transcription factors controls subtype diversification of their progeny.

PMID- 24912778
TI  - Band filling effect on polaron localization in La1-x(Ca(y)Sr1-y)xMnO3 manganites.
AB  - We report on a iSR and 55 Mn NMR investigation of the magnetic order parameter as
      a function of temperature in the optimally doped La(5/8)(CaySr(1.y))(3/8)MnO3 and
      in the underdoped La1.xSrxMnO3 and La1.xCaxMnO3 metallic manganite families. The
      study is aimed at unravelling the effect of lattice distortions, implicitly
      controlled by the Ca-Sr isoelectronic substitution, from that of hole doping x on
      the Curie temperature TC and the order of the magnetic transition. At optimal
      doping, the transitions are second order at all y values, including the y = 1
      (La(5/8)Ca(3/8)MnO3) end member. By contrast, they are first order in the
      underdoped samples, which show a finite (truncated) order parameter at the Curie
      point, including La(0.75)Sr(0.25)MnO3 whose TC is much higher than that of
      La(5/8)Ca(3/8)MnO3. The order parameter curves, on the other hand, exhibit a very
      minor dependence on x, if truncation is excepted. This suggests that the
      effective exchange interaction between Mn ions is essentially governed by local
      distortions, in agreement with the original double-exchange model, while
      truncation is primarily, if not entirely, an effect of under- or over-doping. A
      phase diagram, separating in the x.y plane polaron-driven first order transitions
      from regular second order transitions governed by critical fluctuations, is
      proposed for the La(1.x)(CaySr(1.y))xMnO3 system.

PMID- 24912779
TI  - The SH2 domain is crucial for function of Fyn in neuronal migration and cortical
      lamination.
AB  - Neurons in the developing brain form the cortical plate (CP) in an inside-out
      manner, in which the late-born neurons are located more superficially than the
      early-born neurons. Fyn, a member of the Src family kinases, plays an important
      role in neuronal migration by binding to many substrates. However, the role of
      the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains
      poorly understood. Here, we demonstrate that the SH2 domain is essential for the
      action of Fyn in neuronal migration and cortical lamination. A point mutation in
      the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final
      location in the cerebral cortex, by inducing neuronal aggregation and branching.
      Thus, we provide the first evidence of the Fyn SH2 domain contributing to
      neuronal migration and neuronal morphogenesis.

PMID- 24912780
TI  - Global knockdown of microRNAs affects the expression of growth factors and
      cytokines in human adipose-derived mesenchymal stem cells.
AB  - Cell therapies utilizing mesenchymal stem cells (MSCs) have a great potential in
      many research and clinical settings. The mechanisms underlying the therapeutic
      effects of MSCs have been studied previously and the paracrine effects elicited
      by their production of various growth factors and cytokines were recognized as
      being crucial. However, the molecular controls that govern these paracrine
      effects remain poorly understood. To elucidate the molecular regulators of this
      process, we performed a global knockdown of microRNAs (miRNAs) in human adipose
      derived mesenchymal stem cells (hADSCs) by inhibiting DGCR8, a key protein in
      miRNA biogenesis. Global disruption of miRNA biogenesis in hADSCs caused dramatic
      changes in the expression of subsets of growth factors and cytokines. By
      performing an extensive bioinformatic analysis, we were able to associate
      numerous putative miRNAs with these genes. Taken together, our results strongly
      suggest that miRNAs are essential for the production of growth factors and
      cytokines in hADSCs.

PMID- 24912781
TI  - Critical differences in toxicity mechanisms in induced pluripotent stem cell
      derived hepatocytes, hepatic cell lines and primary hepatocytes.
AB  - Human-induced pluripotent stem cell-derived hepatocytes (hiPSC-Hep) hold great
      potential as an unlimited cell source for toxicity testing in drug discovery
      research. However, little is known about mechanisms of compound toxicity in hiPSC
      Hep. In this study, modified mRNA was used to reprogram foreskin fibroblasts into
      hiPSC that were differentiated into hiPSC-Hep. The hiPSC-Hep expressed
      characteristic hepatic proteins and exhibited cytochrome P450 (CYP) enzyme
      activities. Next, the hiPSC-Hep, primary cryopreserved human hepatocytes (cryo
      hHep) and the hepatic cell lines HepaRG and Huh7 were treated with staurosporine
      and acetaminophen, and the toxic responses were compared. In addition, the
      expression of genes regulating and executing apoptosis was analyzed in the
      different cell types. Staurosporine, an inducer of apoptosis, decreased ATP
      levels and activated caspases 3 and 7 in all cell types, but to less extent in
      Huh7. Furthermore, a hierarchical clustering and a principal component analysis
      (PCA) of the expression of apoptosis-associated genes separated cryo-hHep from
      the other cell types, while an enrichment analysis of apoptotic pathways
      identified hiPSC-Hep as more similar to cryo-hHep than the hepatic cell lines.
      Finally, acetaminophen induced apoptosis in hiPSC-Hep, HepaRG and Huh7, while the
      compound initiated a direct necrotic response in cryo-hHep. Our results indicate
      that for studying compounds initiating apoptosis directly hiPSC-Hep may be a good
      alternative to cryo-hHep. Furthermore, for compounds with more complex mechanisms
      of toxicity involving metabolic activation, such as acetaminophen, our data
      suggest that the cause of cell death depends on a balance between factors
      controlling death signals and the drug-metabolizing capacity.

PMID- 24912782
TI  - The eucalyptus oil ingredient 1,8-cineol induces oxidative DNA damage.
AB  - The natural compound 1,8-cineol, also known as eucalyptol, is a major constituent
      of eucalyptus oil. This epoxy-monoterpene is used as flavor and fragrance in
      consumer goods as well as medical therapies. Due to its anti-inflammatory
      properties, 1,8-cineol is also applied to treat upper and lower airway diseases.
      Despite its widespread use, only little is known about the genotoxicity of 1,8
      cineol in mammalian cells. This study investigates the genotoxicity and
      cytotoxicity of 1,8-cineol in human and hamster cells. First, we observed a
      significant and concentration-dependent increase in oxidative DNA damage in human
      colon cancer cells, as detected by the Formamidopyrimidine-DNA glycosylase (Fpg)
      modified alkaline comet assay. Pre-treatment of cells with the antioxidant N
      acetylcysteine prevented the formation of Fpg-sensitive sites after 1,8-cineol
      treatment, supporting the notion that 1,8-cineol induces oxidative DNA damage. In
      the dose range of DNA damage induction, 1,8-cineol did neither reduce the
      viability of colon cancer cells nor affected their cell cycle distribution,
      suggesting that cells tolerate 1,8-cineol-induced oxidative DNA damage by
      engaging DNA repair. To test this hypothesis, hamster cell lines with defects in
      BRCA2 and Rad51, which are essentials players of homologous recombination (HR)
      mediated repair, were treated with 1,8-cineol. The monoterpene induced oxidative
      DNA damage and subsequent DNA double-strand breaks in the hamster cell lines
      tested. Intriguingly, we detected a significant concentration-dependent decrease
      in viability of the HR-defective cells, whereas the corresponding wild-type cell
      lines with functional HR were not affected. Based on these findings, we conclude
      that 1,8-cineol is weakly genotoxic, inducing primarily oxidative DNA damage,
      which is most likely tolerated in DNA repair proficient cells without resulting
      in cell cycle arrest and cell death. However, cells with deficiency in HR were
      compromised after 1,8-cineol treatment, suggesting a protective role of HR in
      response to high doses of 1,8-cineol.

PMID- 24912783
TI  - Sandwich-cultured rat hepatocytes as an in vitro model to study canalicular
      transport alterations in cholestasis.
AB  - At present, it has not been systematically evaluated whether the functional
      alterations induced by cholestatic compounds in canalicular transporters involved
      in bile formation can be reproduced in sandwich-cultured rat hepatocytes (SCRHs).
      Here, we focused on two clinically relevant cholestatic agents, such as estradiol
      17beta-D-glucuronide (E17G) and taurolithocholate (TLC), also testing the ability
      of dibutyryl cyclic AMP (DBcAMP) to prevent their effects. SCRHs were incubated
      with E17G (200 uM) or TLC (2.5 uM) for 30 min, with or without pre-incubation
      with DBcAMP (10 uM) for 15 min. Then, the increase in glutathione methyl
      fluorescein (GS-MF)-associated fluorescence inside the canaliculi was monitored
      by quantitative time-lapse imaging, and Mrp2 transport activity was calculated by
      measuring the slope of the time-course fluorescence curves during the initial
      linear phase, which was considered to be the Mrp2-mediated initial transport rate
      (ITR). E17G and TLC impaired canalicular bile formation, as evidenced by a
      decrease in both the bile canaliculus volume and the bile canaliculus width,
      estimated from 3D and 2D confocal images, respectively. These compounds decreased
      ITR and induced retrieval of Mrp2, a main pathomechanism involved in their
      cholestatic effects. Finally, DBcAMP prevented these effects, and its well-known
      choleretic effect was evident from the increase in the canalicular volume/width
      values; this choleretic effect is associated in part with its capability to
      increase Mrp2 activity, evidenced here by the increase in ITR of GS-MF. Our study
      supports the use of SCRHs as an in vitro model useful to quantify canalicular
      transport function under conditions of cholestasis and choleresis.

PMID- 24912784
TI  - Reactivation kinetics of 31 structurally different bispyridinium oximes with
      organophosphate-inhibited human butyrylcholinesterase.
AB  - Organophosphorus compounds (OP) are bound to human butyrylcholinesterase (BChE)
      and endogenous or exogenous BChE may act as a stoichiometric scavenger. Adequate
      amounts of BChE are required to minimize toxic OP effects. Simultaneous
      administration of BChE and oximes may transfer the enzyme into a pseudo-catalytic
      scavenger. The present study was initiated to determine the reactivation kinetics
      of 31 structurally different bispyridinium oximes with paraoxon-, tabun- and
      cyclosarin-inhibited human BChE. Human plasma was incubated with OP and the
      reactivation of inhibited BChE was tested with multiple oxime concentrations
      followed by nonlinear regression analysis for the determination of reactivity,
      affinity and overall reactivation constants. The generated data indicate that the
      tested oximes have a low-to-negligible reactivating potency with paraoxon- and
      tabun-inhibited human BChE. Several oximes showed a moderate-to-high potency with
      cyclosarin-inhibited BChE. Thus, the present study indicates that bispyridinium
      oximes are obviously not suitable to serve as reactivators of human BChE
      inhibited by different OP and it is doubtful whether further modifications of the
      bispyridinium template will lead to more potent reactivators. In the end, novel
      structures of oxime and non-oxime reactivators are urgently needed for the
      development of human BChE into an effective pseudo-catalytic scavenger. 

PMID- 24912786
TI  - Urinary bladder cancer risk variants: recent findings and new challenges of GWAS
      and confirmatory studies.

PMID- 24912785
TI  - Exosomal miR-21 derived from arsenite-transformed human bronchial epithelial
      cells promotes cell proliferation associated with arsenite carcinogenesis.
AB  - Intercellular communications within the cancer microenvironment coordinate the
      assembly of various cell types. Exosomes are mediators of intercellular
      communication in immune signaling, tumor promotion, stress responses, and
      angiogenesis. The present research aimed to determine whether miRNAs secreted
      from human bronchial epithelial (HBE) cells transformed by 1.0 MUM arsenite are
      transferred into normal HBE cells and are functionally active in the recipient
      cells. The results show that miR-21 is involved in exosome-mediated intercellular
      communication between neoplastic and normal HBE cells. Exosomes derived from
      transformed HBE cells stimulated proliferation of normal HBE cells, whereas
      exosomes from miR-21 depleted cells failed to stimulate proliferation. In normal
      HBE cells, the expression of phosphatase and tensin homolog, a target gene for
      miR-21, was increased by exosomal miR-21, indicating that exogenous miRNAs, via
      exosomal transport, function-like endogenous miRNAs. Concordantly, specific
      reduction of miR-21 content in exosome-producing transformed cells abolished the
      stimulation of proliferation by exosomes. Collectively, the data indicate that
      transformed HBE cells release exosomes containing miR-21, stimulating
      proliferation in neighboring normal HBE cells and supporting the concept that
      exosomal miRNAs are involved in cell-cell communication during carcinogenesis
      induced by environmental chemicals. 

PMID- 24912787
TI  - Why transparency isn't an unassailable philosophical principle.

PMID- 24912788
TI  - Is transparency really a panacea?

PMID- 24912789
TI  - Dental infections may have detrimental consequences.

PMID- 24912790
TI  - Alienation of the alienist: psychiatry on the ropes?

PMID- 24912791
TI  - Management of pyoderma gangrenosum.
AB  - Pyoderma gangrenosum (PG) is an uncommon ulcerative skin disease often associated
      with underlying systemic diseases. Its pathogenesis is unknown, although immune
      pathways have been implicated. Targeted therapy is therefore lacking and
      currently treatment is largely empirical and consists of corticosteroids and
      ciclosporin first line. This paper reviews the current and emerging knowledge
      about PG. PG occurs with an incidence of 3-10 per million per year. The ulcers
      are exquisitely painful and characteristically have a necrotic centre with
      irregular overhanging bluish borders. Around half of cases are associated with
      underlying systemic disease, most commonly inflammatory bowel disease, rheumatoid
      arthritis and haematological malignancies; the remaining cases are idiopathic.
      The pathogenesis is unknown, but the most widely supported theory is
      immunological, and biopsies of lesions show a predominantly neutrophilic
      infiltrate. Several aberrant immune processes have been described, with
      neutrophils and their recruitment to sites of inflammation by cytokines taking an
      apparently important role. Topical and systemic therapies are both vital aspects
      of treatment, and in recent years, immune modulators have been used with
      increasing success, with an emerging role for anti-tumour necrosis factor alpha
      agents such as the monoclonal antibody infliximab. Although uncommon, PG causes
      significant morbidity to those it affects. Further research is needed into the
      disease pathogenesis, and adequate targeted treatment.

PMID- 24912792
TI  - William Watson's use of controlled clinical experiments in 1767.

PMID- 24912796
TI  - The potential role of direct and indirect bronchial challenge testing to identify
      overtreatment of community managed asthma.
AB  - BACKGROUND: Although airway hyperresponsiveness (AHR) is a defining feature of
      asthma pathophysiology, bronchial challenge testing is not routinely used in
      primary care asthma management. OBJECTIVE: The aim of this study was to evaluate
      the potential role of direct (methacholine) and indirect (mannitol) challenge
      testing in community managed asthma. METHODS: Patients currently treated for
      asthma from Tayside and Fife were identified by the Health Informatics Centre
      (HIC) and invited to take part in the study. At screening, the following tests
      were carried out: spirometry, methacholine and mannitol challenge, exhaled nitric
      oxide (FeNO); Asthma Control Questionnaire (ACQ) and Mini Asthma Quality of Life
      Questionnaire (AQLQ). RESULTS: A total of 3388 asthmatics were initially
      identified by HIC with 423 positive responses and 123 completing the study.
      Seventy percent had either a positive methacholine (PC20  < 8 mg/mL) or mannitol
      challenge (PD15  < 635 mg), and 30% were non-responsive to both challenges.
      Fourteen percent of methacholine responders (n = 74) were negative to mannitol,
      and 16% of mannitol responders (n = 76) were negative to methacholine.
      Spirometry, FeNO, ACQ and AQLQ were significantly better in the non-responder
      group who were exposed to high-dose inhaled corticosteroids and frequent long
      acting beta-agonists. CONCLUSIONS AND CLINICAL RELEVANCE: We found that 30% of
      unselected patients with community managed asthma were challenge negative and
      could be potentially misdiagnosed or overtreated, in turn suggesting the need for
      supervised step-down.

PMID- 24912797
TI  - Population pharmacokinetic modeling of LY2189102 after multiple intravenous and
      subcutaneous administrations.
AB  - Interleukin-1 beta (IL-1beta) is an inflammatory mediator which may contribute to
      the pathophysiology of rheumatoid arthritis (RA) and type 2 diabetes mellitus
      (T2DM). Population pharmacokinetics (PK) of LY2189102, a high affinity anti-IL
      1beta humanized monoclonal immunoglobulin G4 evaluated for efficacy in RA and
      T2DM, were characterized using data from 79 T2DM subjects (Study H9C-MC-BBDK) who
      received 13 weekly subcutaneous (SC) doses of LY2189102 (0.6, 18, and 180 mg) and
      96 RA subjects (Study H9C-MC-BBDE) who received five weekly intravenous (IV)
      doses (0.02-2.5 mg/kg). Frequency of anti-drug antibody (ADA) development appears
      dose-dependent and is different between studies (36.7% in Study H9C-MC-BBDK vs.
      2.1% in Study H9C-MC-BBDE), likely due to several factors, including differences
      in patient population and background medications, administration routes, and
      assays. A two-compartment model with dose-dependent bioavailability best
      characterizes LY2189102 PK following IV and SC administration. Typical
      elimination and distribution clearances, central and peripheral volumes of
      distribution are 0.222 L/day, 0.518 L/day, 3.08 L, and 1.94 L, resulting in a
      terminal half-life of 16.8 days. Elimination clearance increased linearly, yet
      modestly, with baseline creatinine clearance and appears 37.6% higher in subjects
      who developed ADA. Bioavailability (0.432-0.721) and absorption half-life (94.3
      157 h) after SC administration are smaller with larger doses. Overall, LY2189102
      PK is consistent with other therapeutic humanized monoclonal antibodies and is
      likely to support convenient SC dosing.

PMID- 24912798
TI  - Application of a physiologically based pharmacokinetic model informed by a top
      down approach for the prediction of pharmacokinetics in chronic kidney disease
      patients.
AB  - Quantitative prediction of the impact of chronic kidney disease (CKD) on drug
      disposition has become important for the optimal design of clinical studies in
      patients. In this study, clinical data of 151 compounds under CKD conditions were
      extensively surveyed, and alterations in pharmacokinetic parameters were
      evaluated. In CKD patients, the unbound hepatic intrinsic clearance decreased to
      a similar extent for drugs eliminated via hepatic metabolism by cytochrome P450,
      UDP-glucuronosyltransferase, and other mechanisms. Renal clearance showed a
      similar decrease to glomerular filtration rate, irrespective of the contribution
      of tubular secretion. The scaling factor (SF) obtained from the interquartile
      range of the relative change in each parameter was applied to the well-stirred
      model to predict clearance in patients. Hepatic and renal clearance could be
      successfully predicted for approximately half and two-thirds, respectively, of
      the applied compounds, showing the high utility of SFs. SFs were also introduced
      to a physiologically based pharmacokinetic (PBPK) model, and the plasma
      concentration profiles of 12 model compounds with different elimination pathways
      were predicted for CKD patients. The PBPK model combined with SFs provided good
      predictability for plasma concentration. The developed PBPK model with
      information on SFs would accelerate translational research in drug development by
      predicting pharmacokinetics in CKD patients.

PMID- 24912799
TI  - Systematic review with meta-analysis: magnetic resonance enterography vs.
      computed tomography enterography for evaluating disease activity in small bowel
      Crohn's disease.
AB  - BACKGROUND: Magnetic resonance enterography (MRE) has been proposed as a non
      ionising alternative method to computed tomography enterography (CTE). Some
      studies have directly compared CTE and MRE in patients with small bowel Crohn's
      disease (CD) with variable results. AIM: To compare the overall diagnostic
      accuracy in assessing the activity of small bowel and complications. METHODS:
      MEDLINE, EMBASE and Cochrane databases were searched for studies on the accuracy
      of MRE and CTE, as compared with a pre-defined reference standard. Pooled
      sensitivity, specificity, the weighted area under the curve (AUC), incremental
      yield (IY) and other diagnostic indices were evaluated. RESULTS: A total of 290
      CD patients from six different studies were analysed. The pooled sensitivity and
      specificity for MRE in detecting active small bowel CD was 87.9% [95% confidence
      interval (CI), 81.8-92.5] and 81.2% (95% CI: 71.9-88.4) respectively. The AUC
      under the summary receiver-operating characteristic (sROC) of MRE was 0.905 (SEM
      0.03, standard error of the mean). Likewise, the pooled sensitivity and
      specificity of CTE in detecting active small bowel CD was 85.8% (95% CI: 79.2
      90.9) and 83.6% (95% CI: 75.3-90.1) with the AUC of 0.898. The AUC of MRE in
      detecting fistula, stenosis and abscess was 0.936, 0.931 and 0.996, respectively,
      compared to 0.963, 0.616 and 0.899 of CTE. No statistically significant IY for
      MRE vs. CTE was found (fixed model, P > 0.05). CONCLUSIONS: Magnetic resonance
      enterography has a diagnostic effectiveness comparable to computed tomography
      enterography, thus may serve as a radiation-free alternative for evaluation of
      patients with Crohn's disease.

PMID- 24912801
TI  - General health checks don't work.

PMID- 24912800
TI  - Recurrent headache and interpersonal violence in adolescence: the roles of
      psychological distress, loneliness and family cohesion: the HUNT study.
AB  - BACKGROUND: Recurrent headache is the most common and disabling pain condition in
      adolescence. Co-occurrence of psychosocial adversity is associated with increased
      risk of chronification and functional impairment. Exposure to interpersonal
      violence seems to constitute an important etiological factor. Thus, knowledge of
      the multiple pathways linking interpersonal violence to recurrent headache could
      help guide preventive and clinical interventions. In the present study we
      explored a hypothetical causal model where the link between exposure to
      interpersonal violence and recurrent headache is mediated in parallel through
      loneliness and psychological distress. Higher level of family cohesion and male
      sex is hypothesized to buffer the adverse effect of exposure to interpersonal
      violence on headache. METHODS: The model was assessed using data from the cross
      sectional, population-based Young-HUNT 3 study of Norwegian adolescents,
      conducted from 2006-2008. A cohort of 10 464 adolescents were invited. The
      response rate was 73% (7620), age ranged from 12 and 20 years, and 50% (3832)
      were girls. The study comprised self-report measures of exposure to interpersonal
      violence, loneliness, psychological distress and family cohesion, in addition to
      a validated interview on headache, meeting the International Classification of
      Headache Disorders criteria. Recurrent headache was defined as headache recurring
      at least monthly during the past year, and sub-classified into monthly and weekly
      headache, which served as separate outcomes. RESULTS: In Conditional Process
      Analysis, loneliness and psychological distress consistently posed as parallel
      mediating mechanisms, indirectly linking exposure to interpersonal violence to
      recurrent headache. We found no substantial moderating effect of family cohesion
      or sex. CONCLUSIONS: Loneliness and psychological distress seem to play crucial
      roles in the relationship between exposure to interpersonal violence and
      recurrent headache. To facilitate coping and recovery, it may be helpful to
      account for these factors in preventive and clinical interventions. Trauma
      informed, social relationship-based interventions may represent a major
      opportunity to alter trajectories of recurrent headache.

PMID- 24912803
TI  - Otologic characteristics of individuals with deletions of distal 18q.
AB  - OBJECTIVES/HYPOTHESIS: To fully describe the otologic features seen in
      individuals with deletions of the distal long arm of chromosome 18 (distal 18q-).
      STUDY DESIGN: Cross-sectional/observational. METHODS: More than 200 individuals
      with deletions of the long arm of chromosome 18 underwent a complete otologic and
      audiologic examination. In addition, chromosome microarray analysis to determine
      the chromosome copy number was completed for all participants. Overall, 113
      subjects had clinical and audiological data to be reported here. RESULTS: Sixty
      six percent of this population had aural stenosis or atresia. No subject had
      microtia. In the 53 individuals for whom serial data was available, enlargement
      of ear canal diameter was seen in 48% of ears with stenosis, examined over time.
      Abnormalities of the palate were seen in nearly 18% of patients and included
      complete or incomplete clefts of the palate, submucous clefts, and velopharyngeal
      insufficiency. A conductive hearing impairment was identified in 112 ears
      (49.5%), and sensorineural hearing loss was identified in 28%. Eustachian tube
      dysfunction was common and found in 78% of ears examined. CONCLUSIONS: The
      otologic phenotype varies widely among individuals with distal 18q-. External
      auditory canal stenosis without microtia is a hallmark of the disease. Hearing
      impairment is also very common, with both sensorineural losses and conductive
      losses contributing to morbidity. Moreover, the critical region for sensorineural
      hearing loss will aid in the identification of the gene responsible for this
      aspect of the distal 18q- phenotype. LEVEL OF EVIDENCE: 4.

PMID- 24912802
TI  - In vitro assessment of knee MRI in the presence of metal implants comparing
      MAVRIC-SL and conventional fast spin echo sequences at 1.5 and 3 T field
      strength.
AB  - PURPOSE: To assess lesion detection and artifact size reduction of a
      multiacquisition variable-resonance image combination, slice encoding for metal
      artifact correction (MAVRIC-SEMAC) hybrid sequence (MAVRIC-SL) compared to
      standard sequences at 1.5T and 3T in porcine knee specimens with metal hardware.
      MATERIALS AND METHODS: Artificial cartilage and bone lesions of defined size were
      created in the proximity of titanium and steel screws with 2.5 mm diameter in 12
      porcine knee specimens and were imaged at 1.5T and 3T magnetic resonance imaging
      (MRI) with MAVRIC-SL PD and short T1 inversion recovery (STIR), standard fast
      spin echo (FSE) T2 PD, and STIR and fat-saturated T2 FSE sequences. Three
      radiologists blinded to the lesion locations assessed lesion detection rates on
      randomized images for each sequence using receiver operating characteristic
      (ROC). Artifact length and width were measured. RESULTS: Metal artifact sizes
      were largest in the presence of steel screws at 3T (FSE T2 FS: 28.7 cm(2) ) and
      1.5T (16.03 cm(2) ). MAVRIC-SL PD and STIR reduced artifact sizes at both 3T
      (1.43 cm(2) ; 2.46 cm(2) ) and 1.5T (1.16 cm(2) ; 1.59 cm(2) ) compared to FS T2
      FSE sequences (27.57 cm(2) ; 13.20 cm(2) ). At 3T, ROC-derived AUC values using
      MAVRIC-SL sequences were significantly higher compared to standard sequences
      (MAVRIC-PD: 0.87, versus FSE-T2 -FS: 0.73 [P = 0.025]; MAVRIC-STIR: 0.9 vs. T2 
      STIR: 0.78 [P = 0.001] and vs. FSE-T2 -FS: 0.73 [P = 0.026]). Similar values were
      observed at 1.5T. Comparison of 3T and 1.5T showed no significant differences
      (MAVRIC-SL PD: P = 0.382; MAVRIC-SL STIR: P = 0.071). CONCLUSION: MAVRIC-SL
      sequences provided superior lesion detection and reduced metal artifact size at
      both 1.5T and 3T compared to conventionally used FSE sequences. No significant
      disadvantage was found comparing MAVRIC-SL at 3T and 1.5T, although metal
      artifacts at 3T were larger. J. Magn. Reson. Imaging 2015;41:1291-1299. (c) 2014
      Wiley Periodicals, Inc.

PMID- 24912804
TI  - Demographics, clinical characteristics, health resource utilization and cost of
      chronic thromboembolic pulmonary hypertension patients: retrospective results
      from six European countries.
AB  - BACKGROUND: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) results from
      incomplete resolution of a pulmonary embolus, leading to pulmonary hypertension
      and progressive right heart failure and death. We aimed to describe the
      demographics, treatment patterns, health resource utilization and related costs
      of patients with CTEPH. METHODS: In specialized PH centres across six European
      countries, medical charts of CTEPH patients on PH medication were retrospectively
      extracted (chart review between 2006 and 2009). Resource utilization was valued
      using country-specific unit costs. Descriptive statistical analyses were
      performed. RESULTS: Twenty-one hospitals documented 119 consecutive CTEPH
      patients over an average of 25.4 months. Patients were inoperable (83.9%) or
      persistent after surgery (16.0%) with mean age 67.5 +/- 12.3 years, 61% were
      female. The average 6-minute walking distance was 298 +/- 120 meters, and NYHA
      class II/III/IV was 27/59/14%. At baseline, 59.7% patients received endothelin
      receptor antagonist, 34.4% phosphodiesterase-5 inhibitors, and 5.8% prostacyclin.
      Adding a second PH medication was the most common regimen change. CTEPH patients
      experienced 1.8 +/- 2.2 hospitalizations per year accounting for 14.8 +/- 26.1
      days in hospital. Patients paid on average 2.8 office visits per year to their
      general practitioner and 1.3 visits to a specialist. Unadjusted annual mortality
      rate was 6.0%. Annual cost of PH specific medication was the predominant economic
      factor averaging ? 36,768 per year. Costs for hospitalizations (? 4,496) and
      concomitant medications (? 2,510) were substantially lower. Other health care
      resource items only accounted for marginal additional costs. CONCLUSION: CTEPH
      patients are characterised by substantial morbidity and mortality. Health care
      utilisation, predominantly due to off-label use of PH drugs, is significant.

PMID- 24912805
TI  - A safe therapeutic apheresis protocol in paediatric patients weighing 11 to 25
      kg.
AB  - BACKGROUND AND OBJECTIVES: Erythrocytapheresis and leukapheresis (LPE) of small
      children are logistically complex and many centres are reluctant to perform these
      procedures. In children, both sickle cell and leukaemic emergencies demand prompt
      action to prevent additional morbidity but detailed protocols for small children
      are lacking, and often are performed using guidelines shown to work in larger
      patients. We report a 3-year experience with children weighing 11-25 kg at a
      large academic medical centre. MATERIALS AND METHODS: All patients were treated
      with the COBE(r) Spectra apheresis system; circuit was primed with blood not
      adjusted for haematocrit and anticoagulant citrate dextrose A was used as
      anticoagulation. Procedures were performed in the paediatric intensive care unit
      by apheresis nursing staff. RESULTS: Twenty-five apheresis procedures in 19
      patients were performed; 17 of 19 patients presented with sickle cell-related
      acute complications and two (2/19) with newly diagnosed acute leukaemia and
      hyperleucocytosis. None of the patients required medications during the
      procedures. Vital signs and clinical condition remained stable and did not worsen
      during or postapheresis. One patient had a delayed haemolytic transfusion
      reaction 1 week posterythrocytapheresis as he developed alloantibodies as a
      result of the procedure. All sickle cell patients achieved a target haematocrit
      of 21-30% and Haemoglobin A of >=68%. Both leukaemia patients who underwent LPE
      had no further signs of leukostasis and achieved marked reductions in leucocyte
      counts. CONCLUSIONS: Apheresis of children weighing 11-25 kg can be safely
      performed without increased morbidity. We outline a protocol that can be used to
      perform apheresis with minimal complications.

PMID- 24912807
TI  - Negative-tone block copolymer lithography by in situ surface chemical
      modification.
AB  - Negative-tone block copolymer (BCP) lithography based on in situ surface chemical
      modification is introduced as a highly efficient, versatile self-assembled
      nanopatterning. BCP blends films consisting of end-functionalized low molecular
      weight poly(styrene-ran-methyl methacrylate) and polystyrene-block-Poly(methyl
      methacylate) can produce surface vertical BCP nanodomains on various substrates
      without prior surface chemical treatment. Simple oxygen plasma treatment is
      employed to activate surface functional group formation at various substrates,
      where the end-functionalized polymers can be covalently bonded during the thermal
      annealing of BCP thin films. The covalently bonded brush layer mediates neutral
      interfacial condition for vertical BCP nanodomain alignment. This straightforward
      approach for high aspect ratio, vertical self-assembled nanodomain formation
      facilitates single step, site-specific BCP nanopatterning widely useful for
      various substrates. Moreover, this approach is compatible with directed self
      assembly approaches to produce device oriented laterally ordered nanopatterns. 

PMID- 24912808
TI  - Sinus node dysfunction and atrial fibrillation: which one dominates?

PMID- 24912806
TI  - Exosomal miRNAs as potential biomarkers of cardiovascular risk in children.
AB  - Intercellular interactions are essential for basic cellular activities and errors
      in either receiving or transferring these signals have shown to cause
      pathological conditions. These signals are not only regulated by membrane surface
      molecules but also by soluble secreted proteins, thereby allowing for an
      exquisite coordination of cell functions. Exosomes are released by cells upon
      fusion of multivesicular bodies (MVB) with the plasma membrane. Their envelope
      reflects their cellular origin and their surface and internal contents include
      important signaling components. Exosomes contain a wide variety of proteins,
      lipids, RNAs, non-transcribed RNAs, miRNAs and small RNAs that are representative
      to their cellular origin and shuttle from donor cells to recipient cells. The
      exosome formation cargo content and delivery is of immense biological interest
      because exosomes are believed to play major roles in various pathological
      conditions, and therefore provide unique opportunities for biomarker discovery
      and development of non-invasive diagnostics when examined in biological fluids
      such as urine and blood plasma. For example, circulating miRNAs in exosomes have
      been applied as functional biomarkers for diagnosis and outcomes prediction,
      while synthetic miRNAs in polymer-based nanoparticles are applicable for
      therapeutics. This review provides insights into the composition and functional
      properties of exosomes, and focuses on their potential value as diagnostic
      markers in the context of cardiovascular disease risk estimates in children who
      suffer from conditions associated with heightened prevalence of adverse
      cardiovascular disease, namely obesity and sleep-disordered-breathing. 

PMID- 24912809
TI  - Pitfalls of robot-assisted radical prostatectomy: a comparison of positive
      surgical margins between robotic and laparoscopic surgery.
AB  - OBJECTIVES: To compare the surgical outcomes of laparoscopic radical
      prostatectomy and robot-assisted radical prostatectomy, including the frequency
      and location of positive surgical margins. METHODS: The study cohort comprised
      708 consecutive male patients with clinically localized prostate cancer who
      underwent laparoscopic radical prostatectomy (n = 551) or robot-assisted radical
      prostatectomy (n = 157) between January 1999 and September 2012. Operative time,
      estimated blood loss, complications, and positive surgical margins frequency were
      compared between laparoscopic radical prostatectomy and robot-assisted radical
      prostatectomy. RESULTS: There were no significant differences in age or body mass
      index between the laparoscopic radical prostatectomy and robot-assisted radical
      prostatectomy patients. Prostate-specific antigen levels, Gleason sum and
      clinical stage of the robot-assisted radical prostatectomy patients were
      significantly higher than those of the laparoscopic radical prostatectomy
      patients. Robot-assisted radical prostatectomy patients suffered significantly
      less bleeding (P < 0.05). The overall frequency of positive surgical margins was
      30.6% (n = 167; 225 sites) in the laparoscopic radical prostatectomy group and
      27.5% (n = 42; 58 sites) in the robot-assisted radical prostatectomy group. In
      the laparoscopic radical prostatectomy group, positive surgical margins were
      detected in the apex (52.0%), anterior (5.3%), posterior (5.3%) and lateral
      regions (22.7%) of the prostate, as well as in the bladder neck (14.7%). In the
      robot-assisted radical prostatectomy patients, they were observed in the apex,
      anterior, posterior, and lateral regions of the prostate in 43.0%, 6.9%, 25.9%
      and 15.5% of patients, respectively, as well as in the bladder neck in 8.6% of
      patients. CONCLUSIONS: Positive surgical margin distributions after robot
      assisted radical prostatectomy and laparoscopic radical prostatectomy are
      significantly different. The only disadvantage of robot-assisted radical
      prostatectomy is the lack of tactile feedback. Thus, the robotic surgeon needs to
      take this into account to minimize the risk of positive surgical margins.

PMID- 24912810
TI  - MUC1 and maltose-binding protein recombinant fusion protein combined with
      Bacillus Calmette-Guerin induces MUC1-specific and nonspecific anti-tumor
      immunity in mice.
AB  - Human mucin 1 (MUC1) is a target for immunotherapy. The major problem associated
      with MUC1-based cancer vaccines is the weakness of the immunogenicity of MUC1.
      The present study aimed to develop an efficient cancer vaccine through generating
      a recombinant fusion protein consisting of MUC1 and maltose-binding protein (MBP)
      by inserting seven tandem repeats encoding the human MUC1 gene into the pMAL-c2
      expression vector. Bacillus Calmette-Guerin (BCG) was used as an adjuvant. MUC1
      was found to predominantly induce T helper type 2 (Th2) cell responses. MUC1/BCG
      and MUC1-MBP were found to generate T helper (Th) type 1 and 2 responses, while
      MUC1-MBP/BCG induced a Th1 immune profile and stimulated MUC1-specific cytotoxic
      T lymphocyte killing activity. MUC1-MBP, as well as MBP and BCG alone were found
      to induce natural killer (NK) cell activity, with MUC1-MBP/BCG observed to
      synergistically induce NK cell activity. Furthermore, MUC1-MBP/BCG significantly
      inhibited MUC1+ B16 cell growth in mice. These findings show that MBP augments
      the immunogenicity of MUC1 and that BCG enhances the efficacy of the MUC1-MBP
      vaccine. Thus, MUC1-MBP/BCG may have potential as a cancer vaccine for clinical
      application. 

PMID- 24912812
TI  - Higher percentage of CD3+CD154+ T lymphocytes predicts efficacy of TNF-alpha
      inhibitors in active axial SpA patients.
AB  - The objective of this study was to evaluate which subtypes of T lymphocytes
      (CD3(+)CD28(+) and CD3(+)CD154(+)) could predict clinical efficacy after TNF
      alpha inhibitor treatment in active axial SpA patients. Patients who fulfilled
      Assessment of SpondyloArthritis international Society (ASAS) criteria for axial
      SpA had a BASDAI of >=40 mm. All patients received TNF-alpha inhibitor treatment
      for 12 weeks. ASAS20 was used to evaluate the effect of the treatment at week 12.
      We detected the percentage of CD3(+)CD28(+) and CD3(+)CD154(+) T lymphocytes on
      lymphocyte cells in the peripheral blood in patients and healthy controls. We
      evaluated whether the percentage of the above subtypes of T lymphocytes could
      predict clinical efficacy by ROC curve analysis. Fifty-eight healthy controls and
      74 active axial SpA patients were included. Mean age was 26.28 +/- 9.08 and 26.95
      +/- 8.13 years for healthy controls and patients, respectively (p = 0.767). The
      percentage of CD3(+)CD154(+) T lymphocytes was significantly higher in axial SpA
      patients than in healthy controls (1.62 +/- 1.89 % vs 0.79 +/- 0.52 %, p <
      0.0005). At baseline, the percentage of CD3(+)CD154(+) T lymphocytes was
      significantly higher in HLA-B27((+)) patients than HLA-B27((-)) ones (HLA-B27(+)
      vs HLA-B27(-):1.77 +/- 1.95 % vs 0.41 +/- 0.27 %, p = 0.005). Compared with
      baseline, the percentage of CD3(+)CD154(+) T lymphocytes significantly decreased
      to 0.87 +/- 0.49 % at week 12 (p < 0.0005). Moreover, we found higher percentage
      of CD3(+)CD154(+) T lymphocytes could predict clinical efficacy of SpA patients
      with TNF-alpha inhibitor treatment (AUC = 0.733, p = 0.014). High percentage of
      CD3(+)CD154(+) is over-expressed on lymphocytes in peripheral blood of active SpA
      patients and can be down-regulated by TNF-alpha inhibitor therapy. High
      percentage of CD3(+)CD154(+) T lymphocytes may predict clinical efficacy of TNF
      alpha inhibitor treatment in active axial SpA patients.

PMID- 24912811
TI  - Simvastatin inhibits inflammation in ischemia-reperfusion injury.
AB  - Ischemia/reperfusion (I/R) is associated with leukocyte accumulation and tissue
      injury. The aim of this research was to investigate the protective effect of
      simvastatin on hind limb I/R inflammation and tissue damage. Mice were subjected
      to hind limb ischemic insult for 2 h and were simultaneously administered an
      intraperitoneal injection of simvastatin (5 mg/kg); this was followed by 36 h of
      reperfusion. Myeloperoxidase (MPO) levels in the muscles of the hind limb were
      determined. CXC chemokines and pro-inflammatory cytokines, such as macrophage
      inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC),
      interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and P-selectin, were
      assessed using enzyme-linked immunosorbent assay (ELISA). Leukocyte rolling and
      adhesion in vitro was assessed to indicate leukocyte recruitment at the site of
      inflammation. Quantitative measurement of skeletal muscle tissue injury was
      performed. The fluorescent dye level in tissue and serum was used to determine
      hind limb vascular leakage and tissue edema after I/R. Systemic and
      differentiated leukocytes were also counted. Simvastatin significantly reduced
      MIP-2, KC, TNF-alpha, MPO, IL-6, and P-selectin levels compared to the sham group
      and I/R plus pretreatment with phosphate-buffered saline (PBS) group (P<0.05).
      Compared to the sham group and I/R plus PBS group, the I/R plus simvastatin group
      had attenuated inflammation, vascular leakage, and muscular damage (P<0.05).
      Simvastatin also significantly inhibited leukocyte rolling and adhesion compared
      to PBS (P<0.05). Our results suggest that simvastatin may be an effective
      protectant against tissue injury associated with I/R.

PMID- 24912813
TI  - Anti-inflammatory effect of thalidomide on H1N1 influenza virus-induced pulmonary
      injury in mice.
AB  - The purpose of this study is to investigate the anti-inflammatory effect of
      thalidomide (Thd) on H1N1-induced acute lung injury in mice. BALB/C mice were
      infected intranasally with influenza A virus (H1N1) and then treated with Thd at
      a dose of 100 or 200 mg/kg/day for 7 days. Weight loss and survival of mice were
      monitored for 14 days after virus challenge, and the serum and lung tissues were
      collected at 4 days for histological and biochemical analysis. The results showed
      that Thd significantly improved the survival rate, reduced the infiltration of
      inflammatory cells and cytokine (e.g., IL-6, TNF-alpha) and chemokine (e.g.,
      RANTES, IP-10) levels, and inhibited activated p-NFkappaB p65 in infected mice.
      These findings suggested that Thd may attenuate H1N1-induced pulmonary injury and
      thus may find use in the treatment of viral diseases.

PMID- 24912814
TI  - Optical imaging of articular cartilage degeneration using near-infrared
      dipicolylamine probes.
AB  - Articular cartilage is the hydrated tissue that lines the ends of long bones in
      load bearing joints and provides joints with a smooth, nearly frictionless
      gliding surface. However, the deterioration of articular cartilage occurs in the
      early stages of osteoarthritis (OA) and is clinically and radiographically
      silent. Here two cationic near infrared fluorescent (NIRF) dipicolylamine (DPA)
      probes, Cy5-DPA-Zn and Cy7-DPA-Zn, were prepared for cartilage degeneration
      imaging and OA early detection through binding to the anionic glycosaminoglycans
      (GAGs). The feasibility of NIRF dye labeled DPA-Zn probes for cartilage
      degeneration imaging was examined ex vivo and in vivo. The ex vivo studies showed
      that Cy5-DPA-Zn and Cy7-DPA-Zn not only showed the high uptake and electrostatic
      attractive binding to cartilage, but also sensitively reflected the change of
      GAGs contents. In vivo imaging study further indicated that Cy5-DPA-Zn
      demonstrated higher uptake and retention in young mice (high GAGs) than old mice
      (low GAGs) when administrated via local injection in mouse knee joints. More
      importantly, Cy5-DPA-Zn showed dramatic higher signals in sham joint (high GAGs)
      than OA side (low GAGs), through sensitive reflecting the change of GAGs in the
      surgical induced OA models. In summary, Cy5-DPA-Zn provides promising visual
      detection for early cartilage pathological degeneration in living subjects. 

PMID- 24912815
TI  - The promotion of osteointegration under diabetic conditions using
      chitosan/hydroxyapatite composite coating on porous titanium surfaces.
AB  - Composited Chitosan/Hydroxyapatite (CS/HA) material coated on titanium surface
      (cTi) is a promising approach to produce biomaterials with better
      osseointegration capacity, but its bio-performance under diabetic conditions and
      the mechanisms involved remain elusive. We propose that the alterations in the
      Wnt/beta-catenin pathway may play a role in mediating the improvement effect of
      cTi on diabetes-induced impaired implant osteointegration. To confirm the
      hypothesis, primary rat osteoblasts incubated on Ti and cTi were subjected to
      normal serum (NS), diabetic serum (DS), DS + Wnt3a (a specific Wnt agonist) and
      DS + Dkk1 (a specific Wnt antagonist) treatment. In vivo study was performed on
      diabetic sheep implanted with Ti or cTi into the bone defect on crista iliaca.
      Results showed that diabetes depressed osteoblast function evidenced by impaired
      cell adhesion and morphology, decreased cell proliferation and ALP activity, and
      higher apoptotic rate on Ti. Importantly, both cTi and Wnt3a treatment
      ameliorated osteoblastic dysfunction and apoptosis under diabetic condition.
      Implantation with cTi significantly improved osteointegration evidenced by Micro
      CT and histological examinations compared with Ti. Moreover, the aforementioned
      promotive effects afforded by cTi were abolished by blocking Wnt pathway with
      Dkk1. Our study explicitly demonstrates that CS/HA composite material improves
      diabetes-induced impaired osteointegration of Ti via the reactivation of Wnt/beta
      catenin pathway and provides a target point for biomaterial modification to
      attain better clinical performance in diabetic patients. 

PMID- 24912816
TI  - An engineered 3D human airway mucosa model based on an SIS scaffold.
AB  - To investigate interrelations of human obligate airway pathogens, such as
      Bordetella pertussis, and their hosts test systems with high in vitro/in vivo
      correlation are of urgent need. Using a tissue engineering approach, we generated
      a 3D test system of the airway mucosa with human tracheobronchial epithelial
      cells (hTEC) and fibroblasts seeded on a clinically implemented biological
      scaffold. To investigate if hTEC display tumour-specific characteristics we
      analysed Raman spectra of hTEC and the adenocarcinoma cell line Calu-3. To
      establish optimal conditions for infection studies, we treated human native
      airway mucosa segments with B. pertussis. Samples were processed for morphologic
      analysis. Whereas our test system consisting of differentiated epithelial cells
      and migrating fibroblasts shows high in vitro/in vivo correlation, hTEC seeded on
      the scaffold as monocultures did not resemble the in vivo situation. Differences
      in Raman spectra of hTEC and Calu-3 were identified in distinct wave number
      ranges between 720 and 1662 cm(-1) indicating that hTEC do not display tumour
      specific characteristics. Infection of native tissue with B. pertussis led to
      cytoplasmic vacuoles, damaged mitochondria and destroyed epithelial cells. Our
      test system is suitable for infection studies with human obligate airway
      pathogens by mimicking the physiological microenvironment of the human airway
      mucosa. 

PMID- 24912817
TI  - Functional surface engineering by nucleotide-modulated potassium channel
      insertion into polymer membranes attached to solid supports.
AB  - Planar solid-supported membranes based on amphiphilic block copolymers represent
      promising systems for the artificial creation of structural surfaces. Here we
      introduce a method for engineering functional planar solid-supported membranes
      through insertion of active biomolecules. We show that membranes based on
      poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PDMS-b-PMOXA)
      amphiphilic diblock copolymers, which mimic natural membranes, are suitable for
      hosting biomolecules. Our strategy allows preparation of large-area, well-ordered
      polymer bilayers via Langmuir-Blodgett and Langmuir-Schaefer transfers, and
      insertion of biomolecules by using Bio-Beads. We demonstrate that a model
      membrane protein, the potassium channel from the bacterium Mesorhizobium loti,
      remains functional after insertion into the planar solid-supported polymer
      membrane. This approach can be easily extended to generate a platform of
      functional solid-supported membranes by insertion of different hydrophobic
      biomolecules, and employing different types of solid substrates for desired
      applications. 

PMID- 24912818
TI  - Liposomes, modified with PTD(HIV-1) peptide, containing epirubicin and celecoxib,
      to target vasculogenic mimicry channels in invasive breast cancer.
AB  - Refractoriness of invasive breast cancer is closely related with the vasculogenic
      mimicry (VM) channels, which exhibit highly drug resistance to conventional
      chemotherapies. In the present study, the nanostructured targeting epirubicin
      plus celecoxib liposomes were developed by modifying a human immunodeficiency
      virus peptide lipid-derivative conjugate (DSPE-PEG2000-PTDHIV-1) for elimination
      of invasive breast cancer cells along with their VM channels. The studies were
      undertaken on invasive human breast cancer MDA-MB-435S cells and MDA-MB-435S
      xenografts in nude mice. The constructed targeting epirubicin plus celecoxib
      liposomes were approximately 100 nm in size. In vitro results showed that the
      targeting liposomes exhibited strong transport ability across cell and nuclei
      membranes of invasive breast cancer, were able to penetrate and destruct the
      invasive breast cancer spheroids, initiated apoptosis via activating apoptotic
      enzymes (caspase 8, 3), and destroyed the VM channels via down-regulating the
      protein indicators (MMP-9, VE-Cad, FAK, EphA2 and HIF-1alpha) in invasive breast
      cancer cells. In vivo results demonstrated that the targeting liposomes displayed
      a prolonged circulation time in blood system, accumulated more in tumor location,
      were able to eliminate the VM channels and angiogenesis in tumor tissues, and
      resulted in a robust overall anticancer efficacy in invasive breast cancer MDA-MB
      435S xenografts in nude mice. In conclusion, the nanostructured targeting
      epirubicin plus celecoxib liposomes could eliminate invasive breast cancer along
      with the VM channels, hence providing a promising strategy for treatment of
      invasive breast cancer. 

PMID- 24912819
TI  - Therapeutic effect of a multi-targeted imidazolium compound in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed lethal
      cancers in the world. We previously showed two imidazolium salts (IBN-1 and IBN
      9) with a moderate efficacy for HCC. Here we report a more potent imidazolium
      compound IBN-65 (1-benzyl-2-phenyl-3-(4-isopropyl)-benzyl-imidazolium chloride)
      and the associated mechanisms of action in a mouse model of HCC. The IC50 of this
      compound in various liver cancer cell lines was around 5 MUm. IBN-65 dose
      dependently arrested cell cycle at G1 phase and was associated with the down
      regulation of the cyclin-dependent kinase-4, -6, cyclin D1, and cyclin E. In
      addition, IBN-65 induced apoptosis by down-regulating Survivin, Bcl-2 and up
      regulating Bax, leading to sequential activation of Caspase-3, Caspase-9 and the
      cleavage of poly(ADP-ribose) polymerase (PARP). Dysregulation of the epidermal
      growth factor receptor (EGFR) signaling network has been frequently reported in
      HCC. We found that IBN-65 displayed a profound inhibitory effect on the
      EGFR/Raf/MEK/ERK signaling at the phosphorylation level. In Huh7 or Hep3B cells,
      pretreatment with IBN-65 attenuated EGF-induced phosphorylation of both EGFR and
      the downstream p44/42 MAPK. A siRNA knockdown of EGFR also proved that IBN-65
      induced apoptosis mostly through inhibiting downstream EGFR pathway signaling,
      much less at the receptor level. Infrequent administration of IBN-65 (i.p., 5
      mg/kg once weekly for four weeks) to mice bearing the Huh7 cells significantly
      reduced the tumor volume by 65% without affecting the body weight. Critically,
      many of the anti-tumor signaling features observed in the HCC cell lines were
      recaptured in the xenografted tissues. Thus, the metal-free imidazolium compound
      IBN-65 could be a potential candidate towards therapeutic development for HCC. 

PMID- 24912820
TI  - Inhibitory effects of prostaglandin E2 on collagen synthesis and cell
      proliferation in human stellate cells from pancreatic head adenocarcinoma.
AB  - BACKGROUND: Several studies have described an increased cyclooxygenase-2 (COX-2)
      expression in pancreatic cancer, but the role of COX-2 in tumour development and
      progression is not clear. The aim of the present study was to examine expression
      of COX-2 in cancer cells and stromal cells in pancreatic cancer specimens, and to
      explore the role of PGE2 in pancreatic stellate cell proliferation and collagen
      synthesis. METHODS: Immunohistochemistry and immunofluorescence was performed on
      slides from whole sections of tissue blocks using antibodies against COX-2 and
      alpha-smooth muscle actin (alphaSMA). Pancreatic stellate cells (PSC) were
      isolated from surgically resected tumour tissue by the outgrowth method. Cells
      were used between passages 4 and 8. Collagen synthesis was determined by [(3)H]
      proline incorporation, or by enzyme immunoassay measurement of collagen C
      peptide. DNA synthesis was measured by incorporation of [(3)H]-thymidine in DNA.
      Cyclic AMP (cAMP) was determined by radioimmunoassay. Collagen 1A1 mRNA was
      determined by RT-qPCR. RESULTS: Immunohistochemistry staining showed COX-2 in
      pancreatic carcinoma cells, but not in stromal cells. All tumours showed positive
      staining for alphaSMA in the fibrotic stroma. Cultured PSC expressed COX-2, which
      could be further induced by interleukin-1beta (IL-1beta), epidermal growth factor
      (EGF), thrombin, and PGE2, but not by transforming growth factor-beta1 (TGFbeta).
      Indirect coculture with the adenocarcinoma cell line BxPC-3, but not HPAFII or
      Panc-1, induced COX-2 expression in PSC. Treatment of PSC with PGE2 strongly
      stimulated cAMP accumulation, mediated by EP2 receptors, and also stimulated
      phosphorylation of extracellular signal-regulated kinase (ERK). Treatment of PSC
      with PGE2 or forskolin suppressed both TGFbeta-stimulated collagen synthesis and
      PDGF-stimulated DNA synthesis. CONCLUSIONS: The present results show that COX-2
      is mainly produced in carcinoma cells and suggest that the cancer cells are the
      main source of PGE2 in pancreatic tumours. PGE2 exerts a suppressive effect on
      proliferation and fibrogenesis in pancreatic stellate cells. These effects of
      PGE2 are mediated by the cAMP pathway and suggest a role of EP2 receptors.

PMID- 24912821
TI  - Autoimmune cytopenias in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary
      autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA),
      immune thrombocytopenia (ITP), pure red cell aplasia, and autoimmune
      granulocytopenia. The distinction of immune cytopenias from cytopenias due to
      bone marrow infiltration, usually associated with a worse outcome and often
      requiring a different treatment, is mandatory. AIHA and ITP are more frequently
      found in patients with unfavorable biological risk factors for CLL. AIC secondary
      to CLL respond less favorably to standard treatments than their primary forms,
      and treating the underlying CLL with chemotherapy or monoclonal antibodies may
      ultimately be necessary.

PMID- 24912822
TI  - Sinomicrobium pectinilyticum sp. nov., a pectinase-producing bacterium isolated
      from alkaline and saline soil, and emended description of the genus
      Sinomicrobium.
AB  - A Gram-reaction-negative, non-spore-forming strain, designated 5DNS001(T), was
      isolated from soil of an ancient salt-extracting facility in China. Analysis of
      the almost-complete 16S rRNA gene sequence of the bacterium suggested that it
      belongs to the genus Sinomicrobium in the family Flavobacteriaceae. It exhibited
      highest 16S rRNA gene sequence similarity with Sinomicrobium oceani SCSIO
      03483(T) (96.3 %), but less than 93 % sequence similarity with members of the
      genera Imtechella, Zhouia and Joostella and other recognized members of the
      family Flavobacteriaceae. The strain was able to hydrolyse pectin and starch by
      producing pectinase and alpha-amylase. The DNA G+C content of the strain was 42.6
      mol%. The major respiratory quinone was MK-6. The major polar lipid detected in
      the strain was phosphatidylethanolamine. The dominant cellular fatty acids were
      iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1omega6c/C16 :
      1omega7c). Based on phenotypic, genotypic, chemotaxonomic and phylogenetic
      analyses, a novel species, Sinomicrobium pectinilyticum, is proposed. The type
      strain is 5DNS001(T) ( = CGMCC1.11000(T) = KCTC23776(T)). 

PMID- 24912823
TI  - Propionibacterium olivae sp. nov. and Propionibacterium damnosum sp. nov.,
      isolated from spoiled packaged Spanish-style green olives.
AB  - Five strains of Gram-stain-positive bacteria were isolated from anomalous
      fermentations occurring in post-packaging of sealed airtight food-grade plastic
      pouches of Spanish-style green olives. These isolates could be grouped into two
      sets, which showed a similarity in their respective 16S rRNA gene sequences of
      98.40 and 98.44 % with Propionibacterium acidipropionici NCFB 563 and 98.33 and
      98.11 % with Propionibacterium microaerophilum M5(T), respectively, and a
      similarity of 99.41 % between them. The 16S rRNA gene phylogeny revealed that the
      isolates grouped into two statistically well-supported clusters separate from P.
      acidipropionici NCFB 563 and P. microaerophilum M5(T). Enzymic activity profiles
      as well as fermentation patterns differentiated these two novel bacteria from
      other members of the genus Propionibacterium. Finally, phenotypic, genotypic and
      phylogenetic data, supported the proposal of two novel species of the genus
      Propionibacterium, for which the names Propionibacterium olivae sp. nov. (type
      strain, IGBL1(T) = CECT 8061(T) = DSM 25436(T)) and Propionibacterium damnosum
      sp. nov. (type strain, IGBL13(T) = CECT 8062(T) = DSM 25450(T)) are proposed. 

PMID- 24912824
TI  - Streptobacillus hongkongensis sp. nov., isolated from patients with quinsy and
      septic arthritis, and emended descriptions of the genus Streptobacillus and
      Streptobacillus moniliformis.
AB  - Two bacterial strains, HKU33(T) and HKU34, were isolated in Hong Kong from the
      pus aspirated from the right peritonsillar abscess of a patient with quinsy and
      the left elbow joint fluid of another patient with tophaceous gout and left elbow
      septic arthritis, respectively. The bacteria were Gram-stain-negative, non
      motile, non-spore-forming, non-haemolytic pleomorphic bacilli. They grew best on
      Columbia agar with 5 % defibrinated sheep blood in an anaerobic environment or
      aerobic environment with 5 % CO2. They also grew on chocolate agar but not on
      MacConkey agar. They were catalase- and cytochrome oxidase-negative. They showed
      a unique profile of enzyme activities distinguishable from their closely related
      species. Phylogenetic analysis of the complete 16S rRNA gene, and partial groEL,
      gyrB and recA gene sequences showed the two isolates formed a distinct branch
      within the family Leptotrichiaceae, being related most closely to Streptobacillus
      moniliformis. Hierarchical cluster analysis of mass spectra of whole-cell protein
      contents showed that strains HKU33(T) and HKU34 were closely related to each
      other, but were distinct from Streptobacillus moniliformis, Sneathia sanguinegens
      and 'Leptotrichia amnionii'. The DNA G+C content of strain HKU33(T) was 26.0+/
      2.1 mol% (mean+/-sd; n = 3). DNA-DNA hybridization demonstrated <=45.02 % DNA
      relatedness between the two isolates and Streptobacillus moniliformis CCUG
      13453(T). A novel species, Streptobacillus hongkongensis sp. nov., is proposed to
      accommodate strains HKU33(T) and HKU34, with HKU33(T) ( = JCM 18691(T) = NCTC
      13659(T) = DSM 26322(T)) designated the type strain. Emended descriptions of the
      genus Streptobacillus and Streptobacillus moniliformis are also given. 

PMID- 24912825
TI  - A detailed insight into drug delivery from PEDOT based on analytical methods:
      effects and side effects.
AB  - The possibility to release drugs from conducting polymers, like polypyrrole or
      poly(3,4-ethylenedioxythiophene) (PEDOT), has been described and investigated for
      a variety of different substances during the last years, showing a wide interest
      in these release systems. A point that has not been looked at so far however is
      the possibility of other substances, next to the intended ones, leaving the
      polymer film under the high voltage excursions during redox sweeping. In this
      study we target this weakness of commonly used detection methods by implementing
      a high precision analytical method (high-performance liquid chromatography) that
      allows a separation and subsequently a detailed quantification of all possible
      release products. We could identify a significantly more complex release behavior
      for a PEDOT:Dex system than has been assumed so far, revealing the active release
      of the monomer upon redox activation. The released EDOT could thereby be shown to
      result from the bulk material, causing a considerable loss of polymer (>10%
      during six release events) that could partly account for the observed degradation
      or delamination effects of drug-eluting coatings. The monomer leakage was found
      to be substantially higher for a PEDOT:Dex film compared to a PEDOT:PSS sample.
      This finding indicates an overestimation of drug release if side products are
      mistaken for the actual drug mass. Moreover the full picture of released
      substances implements the need for further studies to reduce the monomer leakage
      and identify possible adverse effects, especially in the perspective of releasing
      an anti-inflammatory substance for attenuation of the foreign body reaction
      toward implanted electrodes.

PMID- 24912826
TI  - Effect of Sinorhizobium fredii strain Sneb183 on the biological control of
      soybean cyst nematode in soybean.
AB  - The soybean cyst nematode (SCN; Heterodera glycines) is a major detriment to
      soybean production. The endophytic bacterium Sinorhizobium fredii strain Sneb183
      is known to inhibit the activity of SCN. In the present study, soybean seedlings
      were inoculated with Sneb183, to study the penetration juveniles, and their
      development inside the roots. The number of cysts in the soybean roots was also
      examined. The induced systemic resistance in soybean was also examined through
      the split-root system. Our results revealed that the number of juveniles and
      cysts significantly decreased as a result of Sneb183 inoculation. Sneb183 also
      prolonged the developmental stage of SCN in the root to 30 days as compared to 27
      days in the control. Furthermore, the number of nematodes in each stage was lower
      in the Sneb183 treated plants than control plants. We also used a split-root
      system to show that the S. fredii strain Sneb183 induced a systemic resistance to
      SCN infection in soybean. The repression rate of SCN penetration was 38.75%. Our
      study showed that Sneb183 can be an effective biocontrol agent for managing SCN
      infestation in soybean. 

PMID- 24912827
TI  - Spirituality and health care in Iran: time to reconsider.
AB  - Spirituality is increasingly recognized as an essential element of care. This
      article investigates the role of spirituality in Iranian health care system and
      provides some guidelines to integrate spirituality in routine health care
      practice in Iran. 

PMID- 24912829
TI  - The Relationship Between Religious Attitudes, Fear of Death and Dying with
      General Health Condition: A Survey in College Students.
AB  - This study aims to assess the relationship between religious attitudes of Ilam
      universities students (west of Iran), their perspectives about the fear of self
      and other's death and dying, with their general health. This paper is an analytic
      survey in which 351 college students, who were selected by multistage sampling,
      participated. To measure interested variables, Persian format of standardized
      self-administered questionnaires was employed. Religious attitudes with odds
      ratio (OR) of 0.94 (95% CI 0.91-0.97) and fear of self dying with 0.88 (95% CI
      0.81-0.96) were identified as a protective factors against the inappropriate
      general health condition. However, the fear of other's death (OR 1.16; 95% CI
      1.05-1.28) was identified as a risk factor. This study showed that people who had
      more religious attitudes and fear of self dying had better general health as well
      as the fear of other's death had a significant direct relationship with
      inappropriate general health condition.

PMID- 24912828
TI  - 'Give Me a Reason to Live!' Examining Reasons for Living Across Levels of
      Suicidality.
AB  - Scholarly research focusing on social psychological factors (e.g. mental health)
      and social environmental factors (e.g. childhood trauma) has found these measures
      to be correlated with suicidality. However, such literature has tended to
      overlook what may impact one's reasons for living. Using a sample of over 1,200
      students from a Canadian university, the goal of the current study is to
      empirically test, by employing multivariate nested regression models (by levels
      of suicidal behaviour), known and relative unknown correlates with reasons for
      living, with a particular focus on strength of religious faith, which is a well
      known predictor for suicidality, but less studied as a reason for living. Results
      show that, among students with serious suicidal ideation and/or a previous
      suicide attempt, the strongest predictor for student's reasons for living was
      strength of religious faith. Strength of religious faith has seldom been
      acknowledged or identified as an important measure in assessing one's reasons to
      live. These findings have implications for the role of religiosity among
      suicidality research, especially studies that focus on reasons for living. 

PMID- 24912830
TI  - The prevalence, aetiology and management of wounds in a community care area in
      Ireland.
AB  - This study aimed to establish the prevalence and aetiology of wounds, allowing an
      insight into the management of wound care, the use of dressings and the nursing
      time allocated to the provision of wound care in a community setting in Ireland.
      A cross-sectional survey was used, with data collected on all clients in the
      community who received treatment from public health nurses or community
      registered general nurses for wound care over a 1-week period in April 2013. A
      98.9% response rate was realised, and 188 people were identified as having
      wounds, equating to a crude prevalence of 5% of the active community nursing
      caseload. A total of 60% (n=112) had leg ulcers, 22% (n=42) had pressure ulcers,
      16% (n=30) had an acute wound (surgical or traumatic wounds), 1% (n=2) had a
      diabetic foot wound and a further 1% (n=2) had wounds of other aetiologies. The
      mean duration of wounds was 5.41 months. A total of 18% of wounds were identified
      as infected; however, 60% (n=112) of wounds had antimicrobial products in use as
      either a primary or secondary dressing. The study established that there is a
      significant prevalence of wounds in this community care area. There was absence
      of a clinical diagnosis in many cases, and evidence of inappropriate dressing
      use, risking an increase in costs and a decrease in good clinical outcomes. It
      also highlighted the importance of ongoing education and auditing in the
      provision of wound care.

PMID- 24912831
TI  - Exudate: friend or foe?
AB  - Wound exudate is an essential component in the normal process of wound healing.
      However, excess exudate has always been a major challenge for clinicians and a
      source of embarrassment and discomfort for the patient. The challenge for
      healthcare staff is to provide a wound healing environment that offers the
      optimal amount of exudate to promote healing. This article provides the reader
      with an understanding of the benefits and problems associated with exudate. 

PMID- 24912832
TI  - Influencing dressing choice and supporting wound management using remote 'tele
      wound care'.
AB  - This article describes a local involvement in a project to evaluate a remote
      system of wound management, incorporating the use of digital and mobile
      technology. It outlines how this involvement influenced the current system of
      'tele wound care' (remote wound management) in a large community organisation.
      The system allows remote wound assessment, management advice and ongoing
      monitoring of wounds to ensure that the dressing choice remains appropriate and
      that timely wound care support can be provided to community nurses, practice
      nurses and GPs. 

PMID- 24912833
TI  - Educational challenges and requirements for managing leg ulcers in the community.
AB  - The significant impact of leg ulcers upon quality of life and disease burden
      cannot be overemphasised, with the financial and economic impact from an
      individual, local and national perspective being widely acknowledged. This
      article attempts to highlight issues relating to education in leg ulcer
      management while identifying some current and emerging challenges faced in this
      area by professionals. With regard to education, formal training and perception
      of professionals, the provision of more specialised and focused training,
      increased use of patient-related outcome measures and the concept of knowledge
      brokering have been identified as important aspects in the planning and further
      development of education. Issues in the domains of community nursing, technology,
      pain management, nursing diagnosis, availability of research and recurrence were
      also highlighted. 

PMID- 24912834
TI  - Incorporating novel solutions to lower-limb problems into compression
      formularies.
AB  - This study investigates the effect of a new short-stretch two-layer compression
      system in eight patients with common chronic lower-limb conditions in three
      locations in the UK. Chronic leg ulcers are the most common type of lower-limb
      ulceration with 70% caused by chronic venous hypertension. An appropriate level
      of compression is proven to heal chronic venous leg ulcers. The study was only a
      small sample of patients; however, the underlying conditions included chronic
      venous eczema, diabetes, sarcoma, cellulitis and mixed-aetiology ulcers. During
      the study, the UK experienced some of the hottest temperatures in the last 30
      years. This had an impact on five patients, who noted an increase in malodour
      associated with their leg ulcers. CoFlex TLC (Aspen Medical Europe Ltd) foam
      comfort layer is impregnated with cyclodextrin-a naturally based oligosaccharide
      known to reduce malodour. The zinc-impregnated foam bandages in this study were
      viewed very favourably by both patients and staff, particularly those who had
      chronic venous eczema. 

PMID- 24912836
TI  - Measuring the intangible?

PMID- 24912835
TI  - Silicone pressure-reducing pads for the prevention and treatment of pressure
      ulcers.
AB  - Pressure ulcers, a key quality of care indicator, cause emotional distress to the
      patient, affecting quality of life. They also have significant financial
      implications for the NHS. Pressure ulcer prevention and management are
      fundamental aspects of nursing. This article reports on the Wirral Community
      Trust's policy and guidelines for the maintenance of skin integrity. Tissue
      viability nurses have a duty to review and assess new prevention devices and
      dressings as they become available to ensure a high standard of care is provided.
      A report of an evaluation of the use of KerraPro in combination with current best
      practice guidelines for the prevention or treatment of pressure ulcers is
      provided. The author concludes that silicone pressure-reducing pads are a
      valuable tool in the prevention and treatment of pressure ulcers when used in
      combination with recommendations from the latest guidelines. 

PMID- 24912837
TI  - An interview with Richard White.

PMID- 24912838
TI  - Woundcare4Heroes.

PMID- 24912839
TI  - Lindsay Leg Club Foundation.

PMID- 24912840
TI  - Are community nurses prepared for wound debridement?
AB  - Debridement is an essential component of wound care. However, autolysis remains a
      frequently used method of debridement, despite recent recommendations from the
      European Wound Management Association and the National Institute for Health and
      Care Excellence. Community nurses are recognised as front-line clinicians
      participating in debridement interventions. It is essential that community nurses
      are able to deliver the most appropriate debridement method regardless of their
      current skill set. This will require community nurses to revisit the evidence
      base for debridement, reflect on their current methods of debridement and expand
      their skill set when required. Guidance exists to ensure community nurses are
      able to offer appropriate and safe debridement to clients with non-viable tissue
      which is delaying the wound healing process. 

PMID- 24912841
TI  - TIGIT safeguards liver regeneration through regulating natural killer cell
      hepatocyte crosstalk.
AB  - Overactivation of innate immunity, particularly natural killer (NK) cells, is
      harmful to liver regeneration; however, the molecular mechanisms that limit NK
      cell overactivation during liver regeneration are still elusive. Here we show
      that a coinhibitory receptor, T cell Ig and ITIM domain (TIGIT), was selectively
      up-regulated on NK cells, along with high expression of its ligand, poliovirus
      receptor (PVR/CD155), on hepatocytes during liver regeneration. The absence of
      TIGIT impaired liver regeneration in vivo, along with overactivation of NK cells
      and higher NK-derived interferon-gamma (IFN-gamma) production. We also show that
      both depletion of NK cells and deficiency of IFN-gamma, but not deficiency of
      RAG1, rescued impaired liver regeneration caused by the absence of TIGIT.
      Adoptive transfer of Tigit(-/-) NK cells into NK-deficient Nfil3(-/-) mice
      sufficiently led to impairment of liver regeneration. On the other hand,
      silencing PVR in hepatocytes rescued impaired liver regeneration caused by TIGIT
      deficiency in vivo, while blockade of TIGIT in NK-hepatocyte coculture increased
      IFN-gamma production by NK cells in vitro. CONCLUSION: TIGIT is a safeguard
      molecule to improve liver regeneration through negatively regulating NK
      hepatocyte crosstalk. This finding suggests a novel mechanism of NK cell self
      tolerance towards regenerative hyperplasia of the host.

PMID- 24912842
TI  - Effects of anemia and iron deficiency on quality of life in women with heavy
      menstrual bleeding.
AB  - OBJECTIVE: To assess the impact of anemia and iron deficiency on health-related
      quality of life (HRQoL) in women treated for heavy menstrual bleeding (HMB).
      DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Five
      university hospitals in Finland. SAMPLE: A total of 236 women referred for HMB.
      METHODS: Women were randomized to treatment with hysterectomy or a levonorgestrel
      releasing intrauterine system. We defined groups based on women's pretreatment
      hemoglobin [hemoglobin <120 g/L (anemic) vs. hemoglobin >=120 g/L (nonanemic)]
      and serum ferritin (ferritin <15 MUg/L vs. >=15 MUg/L) concentrations. HRQoL was
      compared between groups at baseline, 6 and 12 months after treatment. Hemoglobin
      and ferritin were followed for 5 years. MAIN OUTCOME MEASURES: HRQoL was measured
      by the RAND 36-item health survey (RAND-36), 5-Dimensional EuroQol and two
      questionnaires of mental wellbeing. RESULTS: At baseline, 63 women (27%) were
      anemic and 140 (60%) were severely iron deficient (ferritin <15 MUg/L). Only 8%
      of the anemic women had taken iron supplementation. Twelve months after treatment
      hemoglobin had increased in both hemoglobin groups, but was still significantly
      lower (p < 0.001) in initially anemic women (128 g/L) compared with nonanemic
      women (136 g/L). Twelve months after treatment three domain scores of RAND-36
      increased more (energy, p = 0.002; physical functioning, p = 0.04; social
      functioning, p = 0.05), and anxiety (p = 0.02) and depression scores (p = 0.002)
      decreased more in anemic compared with nonanemic women. Serum ferritin took 5
      years to reach normal levels. CONCLUSIONS: Improved HRQoL after treatment of HMB
      is associated with correction of anemia. Clinicians should actively screen for
      anemia in women with HMB and emphasize early iron substitution as an integral
      part of treatment.

PMID- 24912843
TI  - Acute multilineage (B/myeloid) leukemia with RUNX1 duplication/amplification and
      hypereosinophilia.
AB  - A 14-year-old girl presented with myalgias and decreased energy and was found to
      have a white count of 73,000 with 75% eosinophils. Flow cytometry and
      immunostains showed the blasts in the bone marrow expressed both myeloid and
      lymphoid markers. Patient was diagnosed with acute multilineage (B/Myeloid)
      leukemia. Genetic testing revealed four copies of the RUNX1 gene region in 25.5%,
      with a normal karyotype and no evidence of t(8;21) or t(12;21) by fluorescence in
      situ hybridization. RUNX1 translocations and amplifications have been implicated
      in acute myeloblastic leukemia, acute lymphoblastic leukemia, and MDS, but have
      not yet been seen with acute multilineage leukemia. Additionally, it is unclear
      what the risk stratification of this unique presentation will turn out to be.

PMID- 24912844
TI  - Qualitative findings from an exploratory trial of the Healthy Lifestyles
      Programme (HeLP) and their implications for the process evaluation in the
      definitive trial.
AB  - BACKGROUND: Approximately one third of 10-11 year olds in England are now
      overweight or obese suggesting that population approaches are urgently required.
      However, despite the increasing number of school-based interventions to prevent
      obesity, results continue to be inconsistent and it is still unclear what the
      necessary conditions are that lead to the sustained behaviour change required to
      affect weight status. The Healthy Lifestyles Programme is a theoretically
      informed four phase multi-component intervention which seeks to create supportive
      school and home environments for healthy behaviours. METHODS: A process
      evaluation has run alongside the exploratory trial of the Healthy Lifestyles
      Programme to ascertain the feasibility and acceptability of; the trial design
      (including the trial outcomes) and the HeLP Programme and whether it is able to
      engage schools, children and their families. Data was collected using interviews
      with teachers (n = 12) and parents (n = 17) and six focus groups with children (n
      = 47) and a questionnaire for parents of children in the intervention schools.
      Interview and focus group data relating to the intervention was analysed using
      framework analysis. RESULTS: Four schools and 201 children participated in the
      exploratory trial. The data showed that the trial design was feasible and
      acceptable for schools and children. Three themes emerged for the data in
      relation to the acceptability and feasibility of the HeLP Programme (value,
      compatibility with the curriculum and enjoyment) and two themes emerged in
      relation to engagement ('knowledge and awareness' and 'taking messages on
      board'). The latter could be broken down into 4 subthemes ('initiating discussion
      with family and friends', 'acceptance of family rules', 'increased
      responsibility' and 'the importance of the mode and agent of delivery'). The use
      of highly inclusive and interactive delivery methods where the children were
      encouraged to identify with and take ownership of the healthy lifestyle messages
      were identified as important factors in motivating the children to take the
      messages home, seek parental support and initiate family lifestyle behaviour
      change. CONCLUSION: The process evaluation of the exploratory trial has not only
      provided evidence of the feasibility and acceptability of the Programme, it has
      also allowed an understanding of how HeLP engages schools, children and their
      families. These findings have informed the process evaluation for the definitive
      trial.

PMID- 24912845
TI  - A universal quantitative 1H nuclear magnetic resonance (qNMR) method for
      assessing the purity of dammarane-type ginsenosides.
AB  - INTRODUCTION: Quantitative (1)H-NMR (qNMR) is a well-established method for
      quantitative analysis and purity tests. Applications have been reported in many
      areas, such as natural products, foods and beverages, metabolites,
      pharmaceuticals and agriculture. The characteristics of quantitative estimation
      without relying on special target reference substances make qNMR especially
      suitable for purity tests of chemical compounds and natural products.
      Ginsenosides are a special group of natural products drawing broad attention, and
      are considered to be the main bioactive principles behind the claims of ginsengs
      efficacy. The purity of ginsenosides is usually determined by conventional
      chromatographic methods, although these may not be ideal due to the response of
      detectors to discriminate between analytes and impurities and the long run times
      involved. OBJECTIVE: To establish a qNMR method for purity tests of six dammarane
      type ginsenoside standards. METHODS: Several experimental parameters were
      optimised for the quantification, including relaxation delay (D1), the
      transmitter frequency offset (O1P) and power level for pre-saturation (PL9). The
      method was validated and the purity of the six ginsenoside standards was tested.
      Also, the results of the qNMR method were further validated by comparison with
      those of high performance liquid chromatography. CONCLUSION: The qNMR method was
      rapid, specific and accurate, thus providing a practical and reliable protocol
      for the purity analysis of ginsenoside standards.

PMID- 24912846
TI  - Introduction to CPDD abstracts.

PMID- 24912847
TI  - Craniometric analysis of European Upper Palaeolithic and Mesolithic samples
      supports discontinuity at the Last Glacial Maximum.
AB  - The Last Glacial Maximum (LGM) represents the most significant climatic event
      since the emergence of anatomically modern humans (AMH). In Europe, the LGM may
      have played a role in changing morphological features as a result of adaptive and
      stochastic processes. We use craniometric data to examine morphological diversity
      in pre- and post-LGM specimens. Craniometric variation is assessed across four
      periods--pre-LGM, late glacial, Early Holocene and Middle Holocene--using a
      large, well-dated, data set. Our results show significant differences across the
      four periods, using a MANOVA on size-adjusted cranial measurements. A
      discriminant function analysis shows separation between pre-LGM and later groups.
      Analyses repeated on a subsample, controlled for time and location, yield similar
      results. The results are largely influenced by facial measurements and are most
      consistent with neutral demographic processes. These findings suggest that the
      LGM had a major impact on AMH populations in Europe prior to the Neolithic.

PMID- 24912848
TI  - Electron microscopy of organic-inorganic interfaces: advantages of low voltage.
AB  - Low voltage electron microscopy has been applied to many types of materials in
      the last several decades with great success. The extremely strong interaction of
      the low voltage electrons with the sample gives high scattering contrast, however
      it can also result in significant damage of the specimen. Irreparable damage to
      several types of organic materials results from their large cross section for
      ionization, or radiolysis, at low voltage. Knock-on damage, which is significant
      at high voltages for many ceramics, semiconductors, minerals and ordered
      carbonaceous material such as graphene, is often reduced at low voltages. For
      organics which damage by radiolysis, measured beam stability increases at higher
      voltages, but the mass-thickness contrast is also reduced. An increased defocus
      can be used to generate phase contrast at higher voltages, although it comes at
      the expense of resolution, as the first zero in the contrast transfer function
      moves toward larger length scales with increasing defocus. Several examples of
      low and high voltage (5kV up to 300kV) experimental TEM images of organic
      inorganic interfaces are used to demonstrate these phenomena. 

PMID- 24912849
TI  - Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant
      pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive
      mesothelial proliferations (RMPs). It is uncertain whether miRNAs are useful
      biomarkers for differentiating MPM from RMPs. Thus, we screened with a
      quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in
      formalin-fixed, paraffin-embedded, preoperative diagnostic biopsy samples,
      surgically resected MPM specimens previously treated with chemotherapy, and
      corresponding non-neoplastic pleura (NNP), from five patients. miR-126, miR-143,
      miR-145, and miR-652 were significantly down-regulated (>=twofold) in resected
      MPM and/or chemotherapy-naive diagnostic tumor biopsy samples. The miRNA
      expression pattern was validated by RT-qPCR in a cohort of 40 independent MPMs.
      By performing binary logistic regression on the RT-qPCR data for the four miRNAs,
      the established four-miRNA classifier differentiated MPM from NNP with high
      sensitivity and specificity (area under the curve, 0.96; 95% CI, 0.92-1.00). The
      classifier's optimal logit(P) value of 0.62 separated NNP and MPM samples with a
      sensitivity of 0.95 (95% CI, 0.89-1.00), a specificity of 0.93 (95% CI, 0.87
      0.99), and an overall accuracy of 0.94 (95% CI, 0.88-1.00). The level of miR-126
      in MPM was inversely correlated with that of the known target, the large neutral
      amino acid transporter, small subunit 1 (r = -0.38; 95% CI, -0.63 to -0.06).
      Overall, these results indicate that these four miRNAs may be suitable biomarkers
      for distinguishing MPM from RMPs.

PMID- 24912850
TI  - Incipient white dot fovea syndrome in a child.
AB  - An 8-year-old girl with normal visual acuity was found to have bilateral macular
      lesions on retinal examination. Ocular coherence tomography showed discrete
      perifoveal inner retinal deposits that characterize the "white dot fovea." This
      report documents the clinical presentation of white dot fovea in early childhood,
      suggesting that this condition may represent an isolated foveal dystrophy. 

PMID- 24912851
TI  - Assessing anosognosias after stroke: a review of the methods used and developed
      over the past 35 years.
AB  - This review provides an overview of research into anosognosia after stroke over
      the past 35 years. We are specifically interested in the assessment of
      anosognosia in group studies and in how any changes in assessment procedures have
      impacted the study of anognosia. Our work is based on a systematic review of
      reports drawn from electronic databases covering the period from 1978 to 2013
      (CINAHL, PubMedMEDLINE, PsycINFO, Web of Knowledge). Sixty-four articles met the
      selection criteria. The results of our review show that a deeper understanding
      has evolved of the multifaceted syndrome of anosognosia during the past decade.
      The most recent studies made more extensive use of research, observational and
      performance-based procedures as well as traditional interview methods. Modality
      specificities and patients with language impairment also receive closer
      consideration than earlier. Furthermore, the results are more often obtained from
      homogeneous patient groups. The limitations of recent anosognosia research
      include the diversity of assessment methods used and the variation in the
      assessment times between and within patient groups, and the tendency to rely on
      only 1 method to assess and diagnose anosognosia. In order to improve the
      comparability of anosognosia studies it would be useful to have guidelines for
      the number and type of assessment methods used in studying different subtypes of
      anosognosia, and to focus on homogeneous patient samples. Furthermore, it is
      recommended that more research be done to explore chronic anosognosia and its
      impact on daily living. 

PMID- 24912852
TI  - Early targets of miR-34a in neuroblastoma.
AB  - Several genes encoding for proteins involved in proliferation, invasion, and
      apoptosis are known to be direct miR-34a targets. Here, we used proteomics to
      screen for targets of miR-34a in neuroblastoma (NBL), a childhood cancer that
      originates from precursor cells of the sympathetic nervous system. We examined
      the effect of miR-34a overexpression using a tetracycline inducible system in two
      NBL cell lines (SHEP and SH-SY5Y) at early time points of expression (6, 12, and
      24 h). Proteome analysis using post-metabolic labeling led to the identification
      of 2,082 proteins, and among these 186 were regulated (112 proteins down
      regulated and 74 up-regulated). Prediction of miR-34a targets via bioinformatics
      showed that 32 transcripts held miR-34a seed sequences in their 3'-UTR. By
      combining the proteomics data with Kaplan Meier gene-expression studies, we
      identified seven new gene products (ALG13, TIMM13, TGM2, ABCF2, CTCF, Ki67, and
      LYAR) that were correlated with worse clinical outcomes. These were further
      validated in vitro by 3'-UTR seed sequence regulation. In addition, Michigan
      Molecular Interactions searches indicated that together these proteins affect
      signaling pathways that regulate cell cycle and proliferation, focal adhesions,
      and other cellular properties that overall enhance tumor progression (including
      signaling pathways such as TGF-beta, WNT, MAPK, and FAK). In conclusion, proteome
      analysis has here identified early targets of miR-34a with relevance to NBL
      tumorigenesis. Along with the results of previous studies, our data strongly
      suggest miR-34a as a useful tool for improving the chance of therapeutic success
      with NBL. 

PMID- 24912854
TI  - Development of DArT markers and assessment of diversity in Fusarium oxysporum f.
      sp. ciceris, wilt pathogen of chickpea (Cicer arietinum L.).
AB  - BACKGROUND: Fusarium oxysporum f. sp. ciceris (Foc), the causal agent of Fusarium
      wilt of chickpea is highly variable and frequent recurrence of virulent forms
      have affected chickpea production and exhausted valuable genetic resources. The
      severity and yield losses of Fusarium wilt differ from place to place owing to
      existence of physiological races among isolates. Diversity study of fungal
      population associated with a disease plays a major role in understanding and
      devising better disease control strategies. The advantages of using molecular
      markers to understand the distribution of genetic diversity in Foc populations is
      well understood. The recent development of Diversity Arrays Technology (DArT)
      offers new possibilities to study the diversity in pathogen population. In this
      study, we developed DArT markers for Foc population, analysed the genetic
      diversity existing within and among Foc isolates, compared the genotypic and
      phenotypic diversity and infer the race scenario of Foc in India. RESULTS: We
      report the successful development of DArT markers for Foc and their utility in
      genotyping of Foc collections representing five chickpea growing agro-ecological
      zones of India. The DArT arrays revealed a total 1,813 polymorphic markers with
      an average genotyping call rate of 91.16% and a scoring reproducibility of 100%.
      Cluster analysis, principal coordinate analysis and population structure
      indicated that the different isolates of Foc were partially classified based on
      geographical source. Diversity in Foc population was compared with the phenotypic
      variability and it was found that DArT markers were able to group the isolates
      consistent with its virulence group. A number of race-specific unique and rare
      alleles were also detected. CONCLUSION: The present study generated significant
      information in terms of pathogenic and genetic diversity of Foc which could be
      used further for development and deployment of region-specific resistant
      cultivars of chickpea. The DArT markers were proved to be a powerful diagnostic
      tool to study the genotypic diversity in Foc. The high number of DArT markers
      allowed a greater resolution of genetic differences among isolates and enabled us
      to examine the extent of diversity in the Foc population present in India, as
      well as provided support to know the changing race scenario in Foc population.

PMID- 24912853
TI  - MicroRNA-205 targets tight junction-related proteins during urothelial cellular
      differentiation.
AB  - The mammalian bladder urothelium classified as basal, intermediate, and
      terminally differentiated umbrella cells offers one of the most effective
      permeability barrier functions known to exist in nature because of the formation
      of apical uroplakin plaques and tight junctions. To improve our understanding of
      urothelial differentiation, we analyzed the microRNA (miRNA) expression profiles
      of mouse urinary tissues and by TaqMan miRNA analysis of microdissected
      urothelial layers and in situ miRNA-specific hybridization to determine the
      dependence of these miRNAs on the differentiation stage. Our in situ
      hybridization studies revealed that miR-205 was enriched in the undifferentiated
      basal and intermediate cell layers. We then used a quantitative proteomics
      approach to identify miR-205 target genes in primary cultured urothelial cells
      subjected to antagomir-mediated knockdown of specific miRNAs. Twenty-four genes
      were reproducibly regulated by miR-205; eleven of them were annotated as cell
      junction- and tight junction-related molecules. Western blot analysis
      demonstrated that antagomir-induced silencing of miR-205 in primary cultured
      urothelial cells elevated the expression levels of Tjp1, Cgnl1, and Cdc42.
      Ectopic expression of miR-205 in MDCK cells inhibited the expression of tight
      junction proteins and the formation of tight junctions. miR-205- knockdown
      urothelial cells showed alterations in keratin synthesis and increases of
      uroplakin Ia and Ib, which are the urothelial differentiation products. These
      results suggest that miR-205 may contribute a role in regulation of urothelial
      differentiation by modulating the expression of tight junction-related molecules.

PMID- 24912855
TI  - Chemical characterization of high-temperature arc gasification slag with a focus
      on element release in the environment.
AB  - High-temperature arc gasification (HTAG) has been proposed as a viable technology
      for the generation of energy and the production of saleable byproducts from
      municipal solid waste (MSW). Total concentrations of elements in HTAG slag were
      assessed and indicated a high partitioning of trace elements (Pb, Cd, and As)
      into the flue gas, an issue of concern when assessing the air pollution control
      residues (APCR) status as a hazardous waste. Hazardous waste leaching tests [such
      as the toxicity characteristic leaching procedure (TCLP)] were performed and
      confirmed that the slag did not meet U.S. criteria for a hazardous waste.
      Leaching was assessed using batch and column tests; the results revealed that Sb
      and Al were elevated in respect to risk-based regulatory thresholds. Slag samples
      were carbonated to simulate weathering effects, and although leachable
      concentrations of Al did decrease by an order of magnitude, Sb concentrations
      were found to increase. Low total concentrations of certain trace elements (As,
      Cd, and Pb), with respect to MSW incineration bottom ashes support the potential
      for reuse of HTAG slag; however, leaching of elements (Pb, Al, and Sb) in batch
      and column tests indicate that proper engineering controls would need to be taken
      to ensure protection of water supplies in a reuse application. 

PMID- 24912856
TI  - Expression of vasoactive proteins in gastric antral mucosa reflects vascular
      dysfunction in patients with cirrhosis and portal hypertension.
AB  - BACKGROUND & AIMS: Patients with cirrhosis display hypocontractility of
      splanchnic vessels because of dysregulation of vasoactive proteins, such as
      decreased effect of RhoA/ROCK and increased activity of beta-Arrestin-2 and eNOS.
      However, it is unknown whether the dysregulation of vasoactive proteins is
      displayed in other vessels. We investigated whether expression of vasoactive
      proteins can be evaluated in gastric mucosa vessels. METHODS: Biopsies from the
      gastric mucosa of 111 patients with cirrhosis were collected at three different
      centres and from 13 controls. Forty-nine patients had received TIPS. Portal
      pressure gradient was measured in 49 patients with TIPS and in 16 patients
      without TIPS. Biopsies from the antrum were conserved in formaldehyde for
      immunohistochemistry or shock-frozen for PCR and Western blot. RESULTS: The
      mucosal transcription of vascular markers (alphaSMA, CD31) was higher in
      cirrhotic patients than controls, which was confirmed by immunohistochemistry. On
      average, relative mucosal levels of RhoA and ROCK were lower, while beta-Arrestin
      2 levels were higher in cirrhotic patients compared to controls. Transcriptional
      levels of eNOS increased with presence of ascites and grade of oesophageal
      varices. Patients with TIPS showed less pronounced markers of vascular
      dysfunction in gastric mucosa. CONCLUSION: This is the first evidence that the
      expression of vasoactive proteins in mucosa from the gastric antrum of patients
      with cirrhosis reflects their vascular dysfunction and possibly changes after
      therapeutic interventions.

PMID- 24912857
TI  - Costs of care for lung and colon cancer patients receiving chemotherapy following
      FDA policy changes.
AB  - PURPOSE: Use of erythropoiesis-stimulating agents (ESAs) in US cancer care
      declined amidst post-marketing evidence of adverse effects and the Food and Drug
      Administration's (FDA) addition of a "black-box" warning to product labeling in
      March 2007. Because reduced ESA use may have led to more transfusions or
      increased anemia-related health care needs, we measured the policy's impact on
      health care costs of lung and colon cancer patients receiving chemotherapy.
      METHODS: In a retrospective cohort study of 13,630 lung and 3,198 colon cancer
      patients in the Department of Veterans Affairs (VA) between 2002 and 2008, we
      calculated anemia treatment (ESA and transfusion), cancer- and non-cancer
      related, and total health care costs for the chemotherapy episode of care. We
      used multivariable regression to examine health care costs and utilization
      between patients whose chemotherapy was administered before (PRE) or after (POST)
      March 1, 2007. RESULTS: ESA costs declined and transfusion costs were similar,
      resulting in lower overall POST-period anemia treatment costs (lung, $526 lower,
      P < 0.01; colon, $504 lower, P < 0.01). Other cancer-related health care costs
      increased, resulting in markedly higher POST-period total health care costs
      (lung, $4,706 higher, P < 0.01; colon, $11,414 higher, P < 0.01). CONCLUSIONS:
      Although chemotherapy episode anemia treatment costs declined after the black-box
      warning, the savings were offset by increases in other cancer-related costs.
      Those increases were mainly in outpatient services and pharmacy, suggesting that
      likely drivers include adoption of new high-cost diagnostic approaches and
      therapeutic modalities. Additional research is needed to determine the effects of
      anemia management changes on patient outcomes and to more fully understand cost
      benefit relationships in cancer treatment.

PMID- 24912858
TI  - Dealing with the financial burden of cancer: perspectives of older breast cancer
      survivors.
AB  - PURPOSE: Financial burden among cancer survivors is often overlooked in
      survivorship care planning. Cancer survivors with limited incomes may be
      particularly affected. Yet, little data are available to address financial issues
      among them. Eliciting the survivors' perspectives on how to deal with this
      financial burden is a first crucial step to identifying the means to provide this
      supportive care. METHODS: In this pilot study, three nominal group technique
      (NGT) sessions were conducted with a convenience sample of 23 older breast cancer
      survivors (age 52 to 83) recruited from a county safety net hospital and a
      Comprehensive Cancer Center. One single NGT question was posed in these sessions,
      namely "What could help women deal with the financial burden that cancer brings
      to them and their families?" Survivors responded in an iterative fashion and then
      ranked the most relevant responses. RESULTS: The most relevant responses
      addressed the (1) need for affordable insurance; (2) need to have prompt
      information on treatment costs patients will face, insurance coverage, and
      agencies or programs that provide needed products and services; and (3) need to
      access social workers, navigators, support groups, or others knowledgeable about
      available resources. Survivors also suggested that physicians become aware of
      cancer costs and financial issues faced by patients and consider costs in their
      treatment plans. CONCLUSIONS: Older survivors face financial challenges for which
      there are few available resources. They suggested several avenues to address
      cancer-related financial issues that may be considered in developing supportive
      interventions.

PMID- 24912859
TI  - Diverticulitis occurs early after lung transplantation.
AB  - BACKGROUND: Lung transplantation recipients are at an increased risk for
      developing diverticulitis. However, the incidence and natural history of
      diverticulitis have not been well characterized. Our objective was to identify
      patient and transplant-related factors that may be associated with an increased
      risk of developing diverticulitis in this patient population. MATERIALS AND
      METHODS: This is a retrospective single institution study. All patients who
      received a lung transplant between May 2008 and July 2013 were evaluated using an
      existing lung transplantation database. Patient-related factors, the incidence
      and timing of diverticulitis, and outcomes of medical and surgical management
      were measured. RESULTS: Of the 314 patients who received a lung transplant, 14
      patients (4.5%) developed diverticulitis. All episodes (100%) of diverticulitis
      occurred within the first 2 y after transplantation. Eight patients (57%)
      required surgery with a mortality rate of 12.5%. Six patients (43%) were managed
      medically and did not require surgery with a mean follow-up period of 442 d.
      CONCLUSIONS: Diverticulitis is common after lung transplantation and occurs with
      a higher incidence compared with the general population. Diverticulitis occurs
      early in the posttransplant period, and the majority of patients require surgery.
      Patients who respond promptly to medical treatment may not require elective
      resection. A greater awareness of the risk of diverticulitis in the early
      posttransplant period may allow for earlier diagnosis and treatment.

PMID- 24912860
TI  - [Continuing medical education in nephrology in France: 2014 agenda].

PMID- 24912861
TI  - Characteristics, risk factors and outcomes of adult cancer patients with
      extensively drug-resistant Pseudomonas aeruginosa infections.
AB  - OBJECTIVE: To evaluate the characteristics and outcomes of cancer patients with
      extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. METHODS: This
      was a retrospective cohort of P. aeruginosa infections in cancer patients in
      Crete, Greece. Patients were followed until discharge. Mortality, predictors of
      mortality and risk factors for XDR P. aeruginosa infection were studied. RESULTS:
      Ninety seven episodes (89 patients) of P. aeruginosa infections (52 with
      bacteremia) were included in the study. In 22 cases, the infection was due to XDR
      isolates. All XDR isolates were susceptible to colistin and variably resistant to
      almost all other antibiotics. The multivariate analysis showed that the
      independent risk factors for XDR P. aeruginosa infection were hematologic
      malignancy (OR 40.7, 95 % CI 4.5-367.6) and prior fluoroquinolone use (OR 11.0,
      95 % CI 2.0-60.5); lymphopenia was inversely associated with XDR infections (OR
      0.16, 95 % CI 0.03-0.92). Mortality was 43 %; infection-related mortality was 24
      %. Bacteremia (OR 8.47, 95 % CI 2.38-30.15), infection due to XDR isolates (OR
      5.11, 95 % CI 1.15-22.62) and age (OR 1.05, 95 % CI 1.00-1.09) were independently
      associated with mortality. CONCLUSION: Mortality in cancer patients with P.
      aeruginosa infections was high. Infection due to XDR isolates was independently
      associated with mortality.

PMID- 24912862
TI  - A performance measure for continuity of care after detoxification: relationship
      with outcomes.
AB  - Administrative data from five states were used to examine whether continuity of
      specialty substance abuse treatment after detoxification predicts outcomes. We
      examined the influence of a 14-day continuity of care process measure on
      readmissions. Across multiple states, there was support that clients who received
      treatment for substance use disorders within 14-days after discharge from
      detoxification were less likely to be readmitted to detoxification. This was
      particularly true for reducing readmissions to another detoxification that was
      not followed with treatment and when continuity of care was in residential
      treatment. Continuity of care in outpatient treatment was related to a reduction
      in readmissions in some states, but not as often as when continuity of care
      occurred in residential treatment. A performance measure for continuity of care
      after detoxification is a useful tool to help providers monitor quality of care
      delivered and to alert them when improvement is needed. 

PMID- 24912863
TI  - Smoking cessation treatment among office-based buprenorphine treatment patients.
AB  - Opioid-dependent patients smoke at high rates, and office-based buprenorphine
      treatment provides an opportunity to offer cessation treatment. We examined
      tobacco use and smoking cessation treatment patterns among office-based
      buprenorphine treatment patients. We reviewed records of 319 patients treated
      with buprenorphine from 2005 to 2010. We examined smoking status, cessation
      medication prescriptions, and factors associated with receipt of cessation
      prescriptions. Mean age was 43.9 years; most were men (74.2%) and Hispanic
      (70.9%). At buprenorphine initiation, 21.9% had no documentation of smoking
      status, while 67.4% were current, 10% former, and 0.9% never smokers. Of current
      smokers, 16.8% received smoking cessation prescriptions. Patients retained (vs.
      not retained) in buprenorphine treatment were more likely to receive smoking
      cessation medications (26.3% vs. 11.2%, p<0.005). We observed a high tobacco use
      prevalence among buprenorphine patients, and limited provision of cessation
      treatment. This is a missed opportunity to impact the high tobacco use burden in
      opioid-dependent persons.

PMID- 24912864
TI  - Pharmacological evaluation of R(+)-pulegone on cardiac excitability: role of
      potassium current blockage and control of action potential waveform.
AB  - INTRODUCTION: R(+)-pulegone is a ketone monoterpene and it is the main
      constituent of essential oils in several plants. Previous studies provided some
      evidence that R(+)-pulegone may act on isolated cardiac myocytes. In this study,
      we evaluated in extended detail, the pharmacological effects of R(+)-pulegone on
      cardiac tissue. METHODS: Using in vivo measurements of rat cardiac
      electrocardiogram (ECG) and patch-clamp technique in isolated myocytes we
      determinate the influence of R(+)-pulegone on cardiac excitability. RESULTS: R(+)
      pulegone delayed action potential repolarization (APR) in a concentration
      dependent manner (EC50=775.7+/-1.48, 325.0+/-1.30, 469.3+/-1.91 MUM at 10, 50 and
      90% of APR respectively). In line with prolongation of APR R(+)-pulegone, in a
      concentration-dependent manner, blocked distinct potassium current components
      (transient outward potassium current (I(to)), rapid delayed rectifier potassium
      current (I(Kr)), inactivating steady state potassium current (I(ss)) and inward
      rectifier potassium current (I(K1))) (EC50=1441+/-1.04; 605.0+/-1.22, 818.7+/
      1.22; 1753+/-1.09 MUM for I(to), I(Kr), I(ss) and I(K1), respectively). The
      inhibition occurred in a fast and reversible way, without changing the steady
      state activation curve, but instead shifting to the left the steady-state
      inactivation curve (V1/2 from -56.92+/-0.35 to -67.52+/-0.19 mV). In vivo
      infusion of 100 mg/kg R(+)-pulegone prolonged the QTc (~40%) and PR (~62%)
      interval along with reducing the heart rate by ~26%. CONCLUSION: Taken together,
      R(+)-pulegone prolongs the APR by inhibiting several cardiomyocyte K(+) current
      components in a concentration-dependent manner. This occurs through a direct
      block by R(+)-pulegone of the channel pore, followed by a left shift on the
      steady state inactivation curve. Finally, R(+)-pulegone induced changes in some
      aspects of the ECG profile, which are in agreement with its effects on potassium
      channels of isolated cardiomyocytes.

PMID- 24912865
TI  - Trace element monitoring in the ICU: quality and economic impact of a change in
      sampling practice.
AB  - BACKGROUND & AIMS: Trace elements (TE) are involved in the immune and antioxidant
      defences which are of particular importance during critical illness. Determining
      plasma TE levels is costly. The present quality control study aimed at assessing
      the economic impact of a computer reminded blood sampling versus a risk guided on
      demand monitoring of plasma concentrations of selenium, copper, and zinc.
      METHODS: Retrospective analysis of 2 cohorts of patients admitted during 6 months
      periods in 2006 and 2009 to the ICU of a University hospital. INCLUSION CRITERIA:
      to receive intravenous micronutrient supplements and/or to have a TE sampling
      during ICU stay. The TE samplings were triggered by computerized reminder in 2006
      versus guided by nutritionists in 2009. RESULTS: During the 2 periods 636
      patients met the inclusion criteria out of 2406 consecutive admissions,
      representing 29.7% and 24.9% respectively of the periods' admissions. The 2009
      patients had higher SAPS2 scores (p = 0.02) and lower BMI compared to 2006 (p =
      0.007). The number of laboratory determinations was drastically reduced in 2009,
      particularly during the first week, despite the higher severity of the cohort,
      resulting in a 55% cost reduction. CONCLUSIONS: The monitoring of TE
      concentrations guided by a nutritionist resulted in a reduction of the sampling
      frequency, and targeting on the sickest high risk patients, requiring a
      nutritional prescription adaptation. This control leads to cost reduction
      compared to an automated sampling prescription.

PMID- 24912867
TI  - Insulin influences developmental competence of bovine oocytes cultured in alpha
      MEM plus follicle-simulating hormone.
AB  - The aim of this study was to evaluate the dose-response effect of insulin, plus
      follicle-simulating hormone (FSH) at a fixed concentration, in a serum-free
      defined culture medium (DCM) on the in vitro maturation of bovine cumulus-oocyte
      complexes (COCs). For oocyte nuclear maturation, the expression levels of GDF9,
      GLUT1, PRDX1 and HSP70.1 transcripts related to oocyte and embryo developmental
      competence were analysed. For in vitro maturation (IVM), cumulus-oocyte complexes
      from slaughterhouse ovaries were distributed into four groups based on insulin
      concentration added to serum-free DCM, which was composed of alpha minimum
      essential medium (alpha-MEM), as basal medium: (1) DCM control: 0 ng/ml; (2)
      DCM1: 1 ng/ml; (3) DCM10: 10 ng/ml; and (4) DCM100: 100 ng/ml. After IVM, the
      nuclear status of a sample of oocytes was analysed and the other oocytes were
      submitted for in vitro fertilization (IVF) and in vitro culture (IVC). Different
      concentrations of insulin did not affect significantly the nuclear maturation and
      cleavage rate (72 h post-insemination) across all groups. Blastocyst rate (192 h
      post-insemination) did not differ in DCM control (24.3%), DCM1 (27.0%) and DCM10
      (26.3%) groups, but the DCM100 (36.1%) group showed a greater blastocyst rate (P
      0.05) was observed at the different insulin concentrations. The results indicated
      that insulin added to DCM influenced levels of transcripts related to cellular
      stress (HSP70-1 and PRDX1) and oocyte competence (GDF9) in bovine oocytes and at
      higher concentrations enhanced blastocyst production. 

PMID- 24912866
TI  - Rapid measurement of macronutrients in breast milk: How reliable are infrared
      milk analyzers?
AB  - BACKGROUND & AIMS: Significant biological variation in macronutrient content of
      breast milk is an important barrier that needs to be overcome to meet nutritional
      needs of preterm infants. To analyze macronutrient content, commercial infrared
      milk analyzers have been proposed as efficient and practical tools in terms of
      efficiency and practicality. Since milk analyzers were originally developed for
      the dairy industry, they must be validated using a significant number of human
      milk samples that represent the broad range of variation in macronutrient content
      in preterm and term milk. Aim of this study was to validate two milk analyzers
      for breast milk analysis with reference methods and to determine an effective
      sample pretreatment. Current evidence for the influence of (i) aliquoting, (ii)
      storage time and (iii) temperature, and (iv) vessel wall adsorption on stability
      and availability of macronutrients in frozen breast milk is reviewed. METHODS:
      Breast milk samples (n = 1188) were collected from 63 mothers of preterm and term
      infants. Milk analyzers: (A) Near-infrared milk analyzer (Unity SpectraStar, USA)
      and (B) Mid-infrared milk analyzer (Miris, Sweden) were compared to reference
      methods, e.g. ether extraction, elemental analysis, and UPLC-MS/MS for fat,
      protein, and lactose, respectively. RESULTS: For fat analysis, (A) measured
      precisely but not accurately (y = 0.55x + 1.25, r(2) = 0.85), whereas (B)
      measured precisely and accurately (y = 0.93x + 0.18, r(2) = 0.86). For protein
      analysis, (A) was precise but not accurate (y = 0.55x + 0.54, r(2) = 0.67) while
      (B) was both precise and accurate (y = 0.78x + 0.05, r(2) = 0.73). For lactose
      analysis, both devices (A) and (B) showed two distinct concentration levels and
      measured therefore neither accurately nor precisely (y = 0.02x + 5.69, r(2) =
      0.01 and y = -0.09x + 6.62, r(2) = 0.02 respectively). Macronutrient levels were
      unchanged in two independent samples of stored breast milk (-20  degrees C
      measured with IR; -80  degrees C measured with wet chemistry) over a period of 14
      months. CONCLUSIONS: Milk analyzers in the current configuration have the
      potential to be introduced in clinical routine to measure fat and protein
      content, but will need major adjustments.

PMID- 24912869
TI  - CORR Insights(r): the Chitranjan Ranawat Award: Periarticular injections and
      femoral & sciatic blocks provide similar pain relief after TKA: a randomized
      clinical trial.

PMID- 24912868
TI  - Metabolite characterisation in peritoneal dialysis effluent using high-resolution
      (1) H and (1) H-(13) C NMR spectroscopy.
AB  - Metabolite analysis of peritoneal dialysis (PD) effluent may provide information
      regarding onset and progression of complications associated with prolonged PD
      therapy. In this context, the nuclear magnetic resonance detectable small
      metabolites of PD effluent samples were characterised using high-resolution (1) H
      and (1) H-(13) C NMR spectroscopy. The various spectra were recorded (at 800 MHz
      proton frequency) on PD effluent samples obtained after 4-h (intraperitoneal)
      dwell time from patients with end-stage renal failure and continuing normally on
      PD therapy. In spite of devastating spectral feature of PD effluent due to the
      presence of intense resonances from glucose and lactate, we were able to identify
      53 small endogenous metabolites (including many complex coupled spin systems) and
      more than 90% of the total CH cross peaks of (1) H-(13) C heteronuclear single
      quantum correlation spectrum specific to various metabolites of PD effluent. We
      foresee that the characteristic fingerprints of various metabolites of control PD
      effluent samples will be used to identify and distinguish metabolic differences
      from PD-related complications.

PMID- 24912871
TI  - Secure thermal infrared communications using engineered blackbody radiation.
AB  - The thermal (emitted) infrared frequency bands, from 20-40 THz and 60-100 THz,
      are best known for applications in thermography. This underused and unregulated
      part of the spectral range offers opportunities for the development of secure
      communications. The 'THz Torch' concept was recently presented by the authors.
      This technology fundamentally exploits engineered blackbody radiation, by
      partitioning thermally-generated spectral noise power into pre-defined frequency
      channels; the energy in each channel is then independently pulsed modulated and
      multiplexing schemes are introduced to create a robust form of short-range secure
      communications in the far/mid infrared. To date, octave bandwidth (25-50 THz)
      single-channel links have been demonstrated with 380 bps speeds. Multi-channel
      'THz Torch' frequency division multiplexing (FDM) and frequency-hopping spread
      spectrum (FHSS) schemes have been proposed, but only a slow 40 bps FDM scheme has
      been demonstrated experimentally. Here, we report a much faster 1,280 bps FDM
      implementation. In addition, an experimental proof-of-concept FHSS scheme is
      demonstrated for the first time, having a 320 bps data rate. With both 4-channel
      multiplexing schemes, measured bit error rates (BERs) of < 10(-6) are achieved
      over a distance of 2.5 cm. Our approach represents a new paradigm in the way
      niche secure communications can be established over short links.

PMID- 24912872
TI  - Introduction to ecological description of a community intervention: building
      prevention through collaborative field based research.
AB  - This special issue of the American Journal of Community Psychology is the result
      of a 18-year partnership with Alaska Native communities using collaborative field
      based research methods. Its goal is to provide a case study fulfilling the spirit
      of ecological inquiry, offering a detailed and nuanced description of a community
      intervention. The articles describe the nature of our work, including some of our
      successes, as well as challenges, dilemmas, and even disappointments we
      experienced along the way. Our primary aim was to develop and assess the
      feasibility of a complex, multi-level intervention to increase protective factors
      hypothesized to reduce suicide and alcohol abuse among rural Yup'ik Alaska Native
      youth ages 12-18. The articles that follow include descriptions of the cultural
      context, relevant literature and project history, our methods of community
      engagement in measurement development strategies, an empirical test of the
      prevention model that guided the intervention, the development and implementation
      of the intervention, a feasibility and impact assessment, and an evaluation of
      community engagement. A final article summarizes what is generalizable from the
      work in field based intervention research with rural and culturally distinct
      populations, and future prospects for decolonizing community intervention
      research methods. These papers raise important issues, including (1) need for
      deep, contextual ecological descriptions, (2) reconceptualization of time in the
      research relationship, (3) distinctions between populations and communities, and
      (4) the conflict between values of communities and intervention science. 

PMID- 24912873
TI  - Well-being and social justice among Moroccan migrants in southern Spain.
AB  - The decision to migrate is normally based on expectations of improving one's
      actual living conditions and therefore, one's well-being. However, these
      expectations are not usually met in receiving contexts that relegate newcomers to
      lower power positions. From a liberating community psychology approach, this
      study aims to develop a predictive model of the well-being of Moroccan migrants
      living in southern Spain. Data were collected from a survey sample of 633
      migrants (the average age was 31.9 years and 51.8 % were women) from 20
      territorial units of Andalusia. Through a process of multilevel regression
      analysis, this study reveals that the well-being of the Moroccan community is
      closely determined by the following: (a) the level of social justice in the
      receiving context (openness to diversity of receiving communities, cultural
      sensitivity of community services, and residential integration); and (b) the
      individual strengths of the population (use of active coping strategies,
      satisfaction with the receiving context, and temporal stability in the new
      environment). These results empirically support the impact that different
      ecological levels of analysis have on well-being. Major theoretical contributions
      of the model and useful suggestions for improving migrant well-being are
      discussed. 

PMID- 24912870
TI  - No difference in postoperative pain after arthroscopic versus open rotator cuff
      repair.
AB  - BACKGROUND: Rotator cuff repair is a successful treatment in terms of patient
      satisfaction and pain relief regardless of the repair method. Although
      arthroscopic repair is commonly thought to be less painful than open or miniopen
      repair, studies disagree on this point. QUESTIONS/PURPOSES: We wished to compare
      the results of patient-reported postoperative pain after open versus arthroscopic
      rotator cuff repair and to identify any predictors of various pain outcomes in
      these groups. METHODS: One-hundred two patients (52 with open repair, 50 with
      arthroscopic repair) participated. Preoperatively, patients reported pain levels
      and self-perceived pain tolerance, and they underwent a test for an objective
      measurement of pain tolerance. Intraoperative variables included surgery duration
      and size of the tear. Postoperatively, patients maintained a pain log for 6
      weeks, reporting daily pain (VAS) and narcotic consumption. Outcome variables
      included days to zero pain, the presence of residual pain, weekly pain levels,
      and cumulative 6-week pain level. Age, sex, tear size, pain tolerance, surgery
      duration, and self-reported preoperative pain were analyzed as possible
      predictors of postoperative pain. This study was powered (beta = 0.2 and alpha =
      0.05) to detect a difference of 10% in the VAS and postoperative analgesic use
      with a requirement of 50 patients in each arm. RESULTS: Days to zero pain (mean,
      28.8 days, 95% CI, 24.8-32.8 days versus 27.6 days, 95% CI, 23.3-31.9 days for
      open versus arthroscopic, respectively; p = 0.69) were not different between the
      open and arthroscopic repair groups. There were differences of questionable
      clinical relevance and borderline statistical significance favoring arthroscopic
      intervention in the second postoperative week (2.3 versus 3.2 of 10 on the VAS; p
      = 0.045). Otherwise, no differences were seen between the two groups in terms of
      residual pain, cumulative pain, or medication use. Consistent predictors of
      postoperative pain affecting multiple outcome measures included severe
      preoperative pain, smaller tear size, and female sex. CONCLUSIONS: There were no
      differences of clinically relevant size between arthroscopic and open rotator
      cuff surgery in this comparative series. Therefore, the choice of arthroscopic
      rotator cuff repair should not be based on decreased postoperative pain. LEVEL OF
      EVIDENCE: Level II, therapeutic study. See the Instructions or Authors for a
      complete description of levels of evidence.

PMID- 24912874
TI  - Forward to ecological description of a multi-level community-based cultural
      intervention: reflections on culturally-situated participatory research.

PMID- 24912875
TI  - Separating the wheat from the chaff - a strategy to utilize plant genetic
      resources from ex situ genebanks.
AB  - The need for higher yielding and better-adapted crop plants for feeding the
      world's rapidly growing population has raised the question of how to
      systematically utilize large genebank collections with their wide range of
      largely untouched genetic diversity. Phenotypic data that has been recorded for
      decades during various rounds of seed multiplication provides a rich source of
      information. Their usefulness has remained limited though, due to various biases
      induced by conservation management over time or changing environmental
      conditions. Here, we present a powerful procedure that permits an unbiased trait
      based selection of plant samples based on such phenotypic data. Applying this
      technique to the wheat collection of one of the largest genebanks worldwide, we
      identified groups of plant samples displaying contrasting phenotypes for selected
      traits. As a proof of concept for our discovery pipeline, we resequenced the
      entire major but conserved flowering time locus Ppd-D1 in just a few such
      selected wheat samples - and nearly doubled the number of hitherto known alleles.

PMID- 24912876
TI  - The placental specific gene, PLAC1, is induced by the Epstein-Barr virus and is
      expressed in human tumor cells.
AB  - BACKGROUND: The Epstein-Barr virus (EBV) is a causal agent in a number of
      malignancies in humans including hematopoietic tumors and non-hematopoietic
      tumors. Burkitt's lymphoma cell lines containing the Epstein-Barr virus have been
      shown to form tumors in nude mice while clonal derivatives of such cell lines in
      which the viral genome has been lost do not (JID 177: 1194-1201, 1998; JV 72:
      9150-9156, 1998; JV 68: 6069-6073, 1994). The re-introduction of EBV into these
      EBV negative BLs reconstitutes the tumor phenotype. Thus, EBV-induced cellular
      genes play critical role in EBV-related tumors. METHODS AND RESULTS: In an
      attempt to identify cellular genes regulated by EBV that may contribute to its
      tumorigenic properties, we have enforced genome loss in the Burkitt's lymphoma
      (BL) line, MutuI, by introducing a dominant negative form of the episomal
      replication factor, EBNA1 and carried out gene array analysis. One of the genes
      identified by this analysis is PLAC1, a gene originally identified as being
      expressed exclusively in placental tissue. Real time RT-PCR analysis verified
      higher expression in EBV positive vs. EBV negative Mutu clones. Analysis of a
      panel of RNAs from 20 normal tissues demonstrated the highest level of expression
      in placenta but significant expression was also observed in testis and brain
      cerebellum. PLAC1 expression was also observed in non-BL tumor cell lines derived
      from breast, ovary, and prostate. Lastly, expression of PLAC1 was found to be
      higher in some primary breast tumors compared to normal adjacent tissues.
      CONCLUSION: This data suggests that the EBV-induced PLAC1 is a member of the
      cancer/testis group of tumor antigens.

PMID- 24912877
TI  - Comparison of barbed versus conventional sutures for wound closure of
      radiologically implanted chest ports.
AB  - PURPOSE: To retrospectively compare the incidences of complications with barbed
      suture versus conventional interrupted suture for incision closure in implantable
      chest ports. MATERIALS AND METHODS: A total of 715 power-injectable dual-lumen
      chest ports placed between 2011 and 2013 were studied. Primary outcomes included
      wound dehiscence, local port infection, local infections treated by wound
      packing, early infections within 30 days, and total infections. A multivariate
      analysis of independent risk factors for port infection was also performed.
      RESULTS: A total of 442 ports were closed with nonbarbed suture, versus 273
      closed with barbed suture. Mean catheter-days in the traditional and barbed
      groups were 257.9 (range, 3-722) and 189.1 (range, 13-747), respectively (P <
      .01). The rate of dehiscence with traditional suture (1.6%; seven of 442) was
      significantly higher than that with barbed suture (zero of 273; P = .04).
      Percentage of total infections was also significantly higher with traditional
      suture (9.5% vs 5.1%; P = .03). No difference in rate of infection per 1,000
      catheter-days was seen between traditional and barbed suture groups (0.0035 vs
      0.0026; P = .17). The rate of local infection with traditional suture was
      significantly higher (2.7% vs 0.4%; P = .02). Additionally, multivariate analysis
      identified the use of traditional suture as the only independent risk factor for
      infection (39% vs 25%; P = .03). CONCLUSIONS: Barbed suture for incision closure
      in implantable dual-lumen chest ports was associated with lower rates of
      dehiscence and potentially lower rates of local infectious complications compared
      with traditional nonbarbed suture.

PMID- 24912878
TI  - Polydioxanone biodegradable stent placement in a canine urethral model: analysis
      of inflammatory reaction and biodegradation.
AB  - PURPOSE: To investigate the inflammatory reaction and perform quantitative
      analysis of biodegradation after placement of a polydioxanone (PDO) biodegradable
      stent in a canine urethral model. MATERIALS AND METHODS: PDO biodegradable stents
      were placed in the proximal and distal urethra of nine male mongrel dogs. The
      dogs were euthanized 4 weeks (group A; n = 3), 8 weeks (group B; n = 3), or 12
      weeks (group C; n = 3) after stent placement. The luminal diameter of the stent
      implanted urethra was assessed by follow-up retrograde urethrography, and
      histologic findings were obtained after the dogs were killed. Stents were removed
      after euthanasia, and their surface morphology and molecular weight were
      evaluated. Hematologic examination was performed to evaluate inflammatory
      reaction. RESULTS: Stent placement was technically successful in all dogs. The
      average luminal diameter gradually decreased. The average number of epithelial
      layers (2.93 vs 4.42; P < .001), the average thickness of papillary projection
      (0.80 mm vs 1.28 mm; P < .001), and the average thickness of submucosal fibrosis
      (0.34 mm vs 0.49 mm ; P < .001) were significantly increased in group B versus
      group A. There were no significant differences between group B and group C. The
      average inflammatory cell infiltration did not differ significantly in the three
      groups. Molecular weight losses were 54% in group A and 84% in group B. In group
      C, PDO stents were completely decomposed. CONCLUSIONS: An experimental study in a
      canine urethral model has demonstrated acceptable inflammatory reaction with
      gradually increasing granulation tissue but no luminal obstruction within 12
      weeks.

PMID- 24912880
TI  - Update on innate lymphoid cells in atopic and non-atopic inflammation in the
      airways and skin.
AB  - Innate lymphoid cells (ILC) is the collective term for a group of related innate
      lymphocytes, including NK cells and the more recently appreciated non-NK ILC
      (ILC1, ILC2 and ILC3). ILC all depend on the common gamma-chain of the IL-2
      receptor and the transcription factor Id2. Furthermore, ILC lack rearranged
      antigen-receptors such as those expressed by T and B cells. Recent data indicate
      that non-NK ILC contribute to a wide range of homeostatic and pathophysiological
      processes primarily by virtue of cytokine production. A lot of effort has been
      put into understanding the role for the non-NK ILC in mucosal homeostasis,
      including in the gut and lungs. Recent reports also point towards a role for ILC
      in skin inflammation. In the lung, ILC may propagate stromal-derived danger
      signals, with subsequent induction of mainly type 2 cytokine production. This
      might represent an early trigger of type 2-mediated pathology, which subsequently
      also engages the adaptive immune system. Similarly, in the skin, ILC are well
      placed to sense keratinocyte-derived danger signals in an antigen-independent
      manner. Recent findings link ILC2 to atopic dermatitis and ILC3 to psoriasis. In
      this review, we provide an updated perspective on the role for non-NK ILC in
      atopic and non-atopic inflammation in the airways as well as in the skin.

PMID- 24912879
TI  - Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric
      cancer by activating TGF-beta signalling.
AB  - Gastric cancer (GC) is the fourth most common malignancy in males and the fifth
      most common malignancy in females worldwide. DACH1 is frequently methylated in
      hepatic and colorectal cancer. To further understand the regulation and mechanism
      of DACH1 in GC, eight GC cell lines, eight cases of normal gastric mucosa, 98
      cases of primary GC and 50 cases of adjacent non-tumour tissues were examined.
      Methylation-specific PCR, western blot, transwell assay and xenograft mice were
      used in this study. Loss of DACH1 expression correlated with promoter region
      methylation in GC cells, and re-expression was induced by 5-Aza-2'
      deoxyazacytidine. DACH1 is methylated in 63.3% (62/98) of primary GC and 38%
      (19/50) of adjacent non-tumour tissues, while no methylation was found in normal
      gastric mucosa. Methylation of DACH1 correlated with reduced expression of DACH1
      (P < 0.01), late tumour stage (stage III/IV) (P < 0.01) and lymph node metastasis
      (P < 0.05). DACH1 expression inhibited epithelial-mesenchymal transition and
      metastasis by inhibiting transforming growth factor (TGF)-beta signalling and
      suppressed GC cell proliferation through inducing G2/M phase arrest. The tumour
      size is smaller in DACH1-expressed BGC823 cell xenograft mice than in unexpressed
      group (P < 0.01). Restoration of DACH1 expression also sensitized GC cells to
      docetaxel. These studies suggest that DACH1 is frequently methylated in human GC
      and expression of DACH1 was controlled by promoter region methylation. DACH1
      suppresses GC proliferation, invasion and metastasis by inhibiting TGF-beta
      signalling pathways both in vitro and in vivo. Epigenetic silencing DACH1 may
      induce GC cells' resistance to docetaxel.

PMID- 24912881
TI  - Subsarcolemmal mitochondrial flashes induced by hypochlorite stimulation in
      cardiac myocytes.
AB  - Mitochondrial superoxide flash (mitoflash) reflects quantal and bursting
      superoxide production and concurrent membrane depolarization triggered by
      transient mitochondrial permeability transition in many types of cells, at the
      level of single mitochondria. Here we investigate reactive oxygen species (ROS)
      mediated modulation of mitoflash activity in cardiac myocytes and report a
      surprising finding that hypochlorite ions potently and preferentially triggered
      mitoflashes in the subsarcolemmal mitochondria (SSM), whereas hydrogen peroxide
      (H2O2) elicited mitoflash activity uniformly among SSM and interfibrillar
      mitochondria (IFM). The striking SSM mitoflash response to hypochlorite
      stimulation remained intact in cardiac myocytes from NOX2-deficient mice,
      excluding local NOX2-mediated ROS as the major player. Furthermore, it occurred
      concomitantly with SSM Ca(2+) accumulation and local Ca(2+) and CaMKII signaling
      played an important modulatory role by altering frequency and unitary properties
      of SSM mitoflashes. These findings underscore the functional heterogeneity of SSM
      and IFM and the oxidant-specific responsiveness of mitochondria to ROS, and may
      bear important ramifications in devising therapeutic strategies for the treatment
      of oxidative stress-related heart diseases.

PMID- 24912889
TI  - Reply to D. Tural et al.

PMID- 24912888
TI  - Effects of acute and repeated cocaine on markers for neural plasticity within the
      mesolimbic system in rats.
AB  - RATIONALE: Repeated cocaine is known to induce morphological changes in
      dopaminergic circuits that are known to participate on cocaine-induced addictive
      changes. OBJECTIVE: The objective of the present study was to discern if acute or
      repeated regimens of daily cocaine (10 mg/kg) lead to reliable changes in the
      expression of some protein markers for neural plasticity such as synaptophysin,
      p21-Arc, alpha-tubulin (alpha-tubulin), and stathmin, in the mesolimbic
      dopaminergic circuit. Well-known changes in tyrosine hydroxylase and protein
      kinase A were used for confirming biochemical effects of repeated cocaine.
      Animals were subjected to three treatments: acute injection, 3-day injections, or
      sensitizing cocaine during 3 days followed by challenging doses at days 8 and 18.
      RESULTS: The findings revealed that sensitizing regimen of cocaine increases
      stathmin levels within the nucleus accumbens at day 18 of treatment, not day 8,
      without changes of synaptophysin, p21-Arc, or alpha-tubulin. This neural
      plasticity change seems not to be related to the development of motor
      sensitization. Other neural regions such as prefrontal cortex, dorsal striatum,
      and ventral tegmental area were not found to be affected. Repeated cocaine led to
      well-known short-term augmentation of tyrosine-hydroxylase and protein kinase A
      expressions in the nucleus accumbens, as well as maintained upregulation of
      tyrosine hydroxylase in the ventral tegmental area. CONCLUSIONS: As stathmin is
      an important regulatory protein of microtubule dynamics, this protein change
      would be linked to morphological changes after repeated cocaine. It was confirmed
      that upregulation of tyrosine hydroxylase within the ventral tegmental area may
      participate on the development of motor sensitization.

PMID- 24912890
TI  - Mortality in prostate cancer and use of statins.

PMID- 24912891
TI  - Reply to J. Moline et al.

PMID- 24912892
TI  - Extranodal Marginal Zone Lymphoma Presenting As Miliary Lung Disease.

PMID- 24912893
TI  - Aprepitant versus dexamethasone for delayed emesis: what is the role of the 5
      hydroxytryptamine type 3 receptor antagonist palonosetron?

PMID- 24912894
TI  - Reply to T.L. Ng et al and L. Celio et al.

PMID- 24912895
TI  - Differences in rates of immediate breast reconstruction in Canada and the United
      States: what can we learn?

PMID- 24912896
TI  - Aprepitant versus dexamethasone to prevent delayed emesis after chemotherapy.

PMID- 24912897
TI  - Building a rapid learning health care system for oncology: the regulatory
      framework of CancerLinQ.
AB  - Today is a time of unprecedented opportunity and challenge in health care
      generally and cancer care in particular. An explosion of scientific knowledge,
      the rapid introduction of new drugs and technologies, and the unprecedented
      escalation in the cost of health care challenge physicians to quickly assimilate
      new information and appropriately deploy new advances while also delivering
      efficient and high-quality care to a rapidly growing and aging patient
      population. At the same time, big data, with its potential to drive rapid
      understanding and innovation, promises to transform the health care industry, as
      it has many others already. CancerLinQ is an initiative of the American Society
      of Clinical Oncology (ASCO) and its Institute for Quality, developed to build on
      these opportunities and address these challenges by collecting information from
      the electronic health records of large numbers of patients with cancer.
      CancerLinQ is, first and foremost, a quality measurement and reporting system
      through which oncologists can harness the depth and power of their patients'
      clinical records and other data to improve the care they deliver. The development
      and deployment of CancerLinQ raises many important questions about the use of big
      data in health care. This article focuses on the US federal regulatory pathway by
      which CancerLinQ will accept patient records and the approach of ASCO toward
      stewardship of the information. 

PMID- 24912898
TI  - Long-Term Disease Control in a Patient With Recurrent Bone-Only Oligometastatic
      Nasopharyngeal Carcinoma.

PMID- 24912899
TI  - Trastuzumab-associated cardiac events at 8 years of median follow-up in the
      Herceptin Adjuvant trial (BIG 1-01).
AB  - PURPOSE: To document the rate and outcome of trastuzumab-associated cardiac
      dysfunction in patients following 1 or 2 years of adjuvant therapy. PATIENTS AND
      METHODS: The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial
      comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients
      with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast
      cancer. Cardiac function was closely monitored. Eligible patients had left
      ventricular ejection fraction (LVEF) >= 55% at study entry following neoadjuvant
      chemotherapy with or without radiotherapy. This 8-year median follow-up analysis
      considered patients randomly assigned to 2 years or 1 year of trastuzumab or
      observation. RESULTS: The as-treated safety population for 2 years of trastuzumab
      (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is
      reported. Cardiac adverse events leading to discontinuation of trastuzumab
      occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year
      arm. Cardiac death, severe congestive heart failure (CHF), and confirmed
      significant LVEF decrease remained low in all three arms. The incidence of severe
      CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease
      (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1
      year trastuzumab arms compared with the observation arm. Severe CHF was the same
      for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease
      receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with
      confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute
      recovery. CONCLUSION: Long-term assessment at 8-year median follow-up confirms
      the low incidence of cardiac events for trastuzumab given sequentially after
      chemotherapy and radiotherapy, and cardiac events were reversible in the vast
      majority of patients.

PMID- 24912900
TI  - Surgeon influence on use of needle biopsy in patients with breast cancer: a
      national medicare study.
AB  - PURPOSE: Use of needle biopsy is a proposed quality measure in the diagnosis and
      treatment of breast cancer, yet prior literature documents underuse. Nationally,
      little is known regarding the contribution of a patient's surgeon to needle
      biopsy use, and knowledge regarding downstream impact of needle biopsy on breast
      cancer care is incomplete. METHODS: Using 2003 to 2007 nationwide Medicare data
      from 89,712 patients with breast cancer and 12,405 surgeons, logistic regression
      evaluated the following three outcomes: surgeon consultation before versus after
      biopsy, use of needle biopsy (yes or no), and number of surgeries for cancer
      treatment. Multilevel analyses were adjusted for physician, patient, and
      structural covariates. RESULTS: Needle biopsy was used in 68.4% (n = 61,353) of
      all patients and only 53.7% of patients seen by a surgeon before biopsy (n =
      32,953/61,312). Patient factors associated with surgeon consultation before
      biopsy included Medicaid coverage, rural residence, residence more than 8.1 miles
      from a radiologic facility performing needle biopsy, and no mammogram within 60
      days before consultation. Among patients with surgeon consultation before biopsy,
      surgeon factors such as absence of board certification, training outside the
      United States, low case volume, earlier decade of medical school graduation, and
      lack of specialization in surgical oncology were negatively correlated with
      receipt of needle biopsy. Risk of multiple cancer surgeries was 33.7% for
      patients undergoing needle biopsy compared with 69.6% for those who did not
      (adjusted relative risk, 2.08; P < .001). CONCLUSION: Needle biopsy is underused
      in the United States, resulting in a negative impact on breast cancer diagnosis
      and treatment. Surgeon-level interventions may improve needle biopsy rates and,
      accordingly, quality of care.

PMID- 24912901
TI  - Effect of communication skills training program for oncologists based on patient
      preferences for communication when receiving bad news: a randomized controlled
      trial.
AB  - PURPOSE: The aim of this study was to identify the effects of a communication
      skills training (CST) program for oncologists, developed based on patient
      preferences regarding oncologists' communication. PARTICIPANTS AND METHODS:
      Thirty oncologists were randomly assigned to either an intervention group (IG; 2
      day CST workshop) or control group (CG). Participants were assessed on their
      communication performance during simulated consultation and their confidence in
      communicating with patients at baseline and follow-up. A total of 1,192 patients
      (response rate, 84.6%) who had consultations with the participating oncologists
      at baseline and/or follow-up were assessed regarding their distress using the
      Hospital Anxiety and Depression Scale, satisfaction with the consultation, and
      trust in their oncologist after the consultation. RESULTS: At the follow-up
      survey, the performance scores of the IG had improved significantly, in terms of
      their emotional support (P = .011), setting up a supportive environment (P =
      .002), and ability to deliver information (P = .001), compared with those of the
      CG. Oncologists in the IG were rated higher at follow-up than those in the CG in
      terms of their confidence in themselves (P = .001). Patients who met with
      oncologists after they had undergone the CST were significantly less depressed
      than those who met with oncologists in the CG (P = .027). However, the CST
      program did not affect patient satisfaction with oncologists' style of
      communication. CONCLUSION: A CST program based on patient preferences is
      effective for both oncologists and patients with cancer. Oncologists should
      consider CST as an approach to enhancing their communication skills.

PMID- 24912902
TI  - Equality in lynch syndrome screening: why should we hold patients with
      endometrial cancer to a different standard?

PMID- 24912903
TI  - The PM2.5 chemical composition in an industrial zone included in a large urban
      settlement: main sources and local background.
AB  - Chemical analyses, receptor modeling and meteorological data were combined to
      determine the composition and sources of PM2.5 sampled daily in a large area in
      Italy characterized by a high number of heterogeneous industrial emissions and
      contiguous to a major urban center. The PM2.5 local background in the area, i.e.
      the common basic composition and concentrations of PM2.5, was determined. Factor
      analysis-multiple linear regression analysis (FA-MLRA) was used to identify and
      quantify the main PM sources. Groups of samples with similar source contributions
      were then sorted using cluster analysis. The potential source location and the
      influence of long range transport were investigated by using the conditional
      probability function (CPF) and the potential source contribution function (PSCF)
      respectively. On an annual basis, five sources of PM were found relevant.
      Industrial emissions accounted for 3% of PM mass, whereas the main contribution
      to PM was related to a combination of ammonium nitrate, combustion (54%) and road
      traffic (36%), mainly related to urban emissions. The PM2.5 background was
      estimated to account for 20 MUg m(-3). It comprises contributions of 55% ammonium
      nitrate and combustion, 46% road traffic, 6% fossil fuel combustion and 3%
      industrial emissions. Source contributions are influenced by both local
      atmospheric circulation and regional transport.

PMID- 24912904
TI  - Linear and nonlinear ac susceptibilities in polycrystalline low-bandwidth Pr1
      xCa(x)MnO3(x = 0.0 - 0.3) manganite.
AB  - The complex linear and nonlinear ac susceptibility have been thoroughly
      investigated in the low bandwidth manganite compound Pr(1-x)Ca(x)MnO3 (PCMO) for
      the doping range x = 0.0-0.3 with and without a superimposed background dc field.
      The dynamical ac response shows substantial differences between the samples. The
      sample with x = 0.1 is found to have two separate magnetic transition peaks,
      compared to the single transitions in the samples x = 0.0 and x = 0.2. The
      nonlinear ac susceptibility measurements were compared between samples, which
      confirmed that these transition peaks are similar in nature and from the same
      magnetic origin. Additionally, for sample x = 0.3 a complex transition peak
      structure with overlapping transition peaks was found. This kind of evolution of
      the magnetic phases as a function of the Ca concentration is believed to rise
      from coexisting antiferromagnetic (AFM) and ferromagnetic (FM) orderings, where
      the Ca concentration controls the amount of FM clusters in the sample. The spin
      glass characteristics of these complex phase-separated magnetic regimes showed
      similarities and contradictions with conventional spin glasses, which indicates
      that this cluster glass behavior arises from the frustration between competing
      AFM and FM clusters having different magnetic exchange interaction.

PMID- 24912905
TI  - [Cow's milk protein allergy in disability children].
AB  - BACKGROUND: Cow's milk protein allergy (CMPA) is the most common food allergy in
      children. However, the prevalence of CMPA in disability children is unknown.
      OBJECTIVE: To know the frequency of CMPA in disability children and to assess the
      clinical improvement after a suppression diet. MATERIAL AND METHODS: We conducted
      a cohort study at the Children's Rehabilitation Center Telethon of Puebla, in
      which children aged 6 months to 5 years with clinical symptoms of CMPA were
      included, between January and September 2012. An exploratory questionnaire about
      clinical symptoms of CMPA was applied before and after the cow's milk proteins
      suppression diet. RESULTS: We identified 26 cases among 145 assessed children
      (18%). The mean age was 2 years and 7 months. All children had a history of
      multiple clinical symptoms. Respiratory symptoms were the most common, follows
      for gastrointestinal symptoms, including regurgitation, which suggests the
      association with gastroesophageal reflux. CONCLUSIONS: CMPA is frequent in
      disability children. Respiratory and gastrointestinal symptoms were the most
      common. Cow's milk proteins suppression diet was a useful diagnostic and therapy
      tool for these children.

PMID- 24912906
TI  - [Association between unplanned pregnancy and adolescence onset asthma].
AB  - BACKGROUND: The association between asthma and pregnancy has been documented
      previously. The relationship between unplanned pregnancy and onset asthma in
      adolescence has not been studied. OBJECTIVE: To determine the association between
      unplanned pregnancy and adolescence onset asthma. MATERIAL AND METHODS: A cross
      sectional study was done gathering information about asthma, unplanned pregnancy,
      family atopy and active or passive smoking in 3,130 adolescents aged 13-19 years.
      Asthma diagnosis was established through a selfquestionnaire based on the
      International Study of Asthma and Allergy in Childhood. Odds ratios for asthma
      were determined using logistic regression model and chi-squared test. RESULTS:
      Mean age of the participants was 16.37 +/- 1.93 years. The prevalence of active
      smoking was 16.1%, of passive smoking 40% and of family atopy 9.8%. From the
      pregnant adolescents (785), 59.5% reported had planned not to have a child before
      pregnancy. Prevalence of wheezing during the year prior to the study was 9.3% and
      of wheezing during the pregnancy 2%. The prevalence of adolescence onset asthma
      was 5.4%. The age of initiation of asthma in the adolescence was 14.75 +/- 1.60
      years. The analysis showed that unplanned pregnancy has a slight risk for the
      development of asthma during adolescence. (Crude OR=1.03; CI 95% 1.02-1.05;
      p=0.000). CONCLUSION: Unplanned pregnancy, family atopy, active smoking and
      smoking friends are associated with the onset-asthma in the adolescence.

PMID- 24912908
TI  - [Assessment of hypersensitivity to honey-bee venom in beekeepers by skin tests].
AB  - BACKGROUND: Beekeepers are exposed to frequent honey-bee stings, and have the
      risk to develop hypersensitivity to bee venom, but long-term exposure can induce
      immune tolerance in them. Up to 30% of beekeepers show positive skin tests with
      honey-bee venom. The prevalence of systemic reactions to bee stings in beekeepers
      is from 14% to 42%. OBJECTIVE: To know the prevalence of hypersensitivity to
      honeybee venom in Mexican beekeepers and non-beekeepers by the use of skin tests.
      MATERIAL AND METHODS: A group of 139 beekeepers and a group of 60 non-beekeeper
      volunteers had a history and physical related to age, sex, family and personal
      atopic history and time of exposure to bee stings. Both groups received
      intradermal skin tests with honey-bee venom, 0.1 mcg/mL and 1 mcg/mL, and
      histamine sulphate 0.1 mg/mL and Evans solution as controls. The skin tests
      results of both groups were compared by chi-squared test. RESULTS: Of the group
      of beekeepers, 116 were men (83%) and 23 women, average age was 39.3 years, had
      atopic family history 28% and personal atopy 13%, average time of exposure to bee
      stings was 10.9 years, skin tests with honey-bee venom were positive in 16.5% and
      11% at 1 mcg/mL and 0.1 mcg/mL, respectively. In the non-beekeepers group venom
      skin tests were positive in 13.3% and 6.7% at 1 mcg/mL and 0.1 mcg/mL. We did not
      find significant differences between the two venom concentrations tested in both
      groups, neither in the number of positive skin tests between the two groups.
      CONCLUSIONS: We found hypersensivity to honey-bee venom slightly higher in the
      beekeepers than in the group apparently not exposed. Both honey-bee venom
      concentrations used did not show difference in the results of the skin tests. The
      similarity of skin tests positivity between both groups could be explained by
      immune tolerance due to continued exposure of beekeepers.

PMID- 24912907
TI  - [Association between Helicobacter pylori and allergic and non-allergic chronic
      urticaria].
AB  - BACKGROUND: Chronic urticaria is characterized by swelling and itchy hives
      presenting remissions and exacerbations, for six weeks or more, which may or may
      not be accompanied by angioedema. Helicobacter pylori infection has been
      associated with various diseases among them chronic urticaria. OBJECTIVE: To
      determine the association between H. pylori infection and allergic and non
      allergic chronic urticaria. MATERIAL AND METHOD: We conducted a retrospective,
      observational and cross-sectional study which included 82 patients of both sexes
      with a diagnosis of chronic urticaria, aged between 2 and 75 years. Total serum
      IgE and IgG anti-H. pylori were measured in all participants. Statistical
      analysis was performed using the chi-squared test with 0.05 significance.
      RESULTS: A total of 82 patients, 33 males and 49 females, with a mean age of 36.9
      years were studied. H. pylori seropositivity was in 65.2% of allergic patients
      and 34.8% of non-allergic patients (p = 0.148). CONCLUSIONS: We found no
      association between chronic allergic urticaria and H. pylori infection.

PMID- 24912909
TI  - Anaphylaxis. How often patients carry epinephrine in real life?
AB  - BACKGROUND: Epinephrine is an important life-saving treatment in patients with
      anaphylaxis. OBJECTIVE: To evaluate how many patients with a history of
      anaphylaxis, carry epinephrine with them during medical consultation. MATERIAL
      AND METHODS: A prospective study was done in the Allergy Unit of the University
      of Antioquia (Medellin, Colombia), we recruited patients, of all ages, from
      August 2012 to June 2013, who were referred with suspected anaphylactic reaction
      for the last 18 months, and were asked about carrying epinephrine with them.
      RESULTS: Among 120 patients with a history of anaphylaxis, only 69 (57.5%) had
      epinephrine in their house or office, and 33 (27.5%) carried it in the medical
      consultation after 6 months of being prescribed. CONCLUSIONS: Most patients with
      a history of anaphylaxis do not carry epinephrine with them all the time, and it
      is necessary to advise the patients, to improve their compliance to treatment.

PMID- 24912910
TI  - The ocular surface: from physiology to the ocular allergic diseases.
AB  - Allergic conjunctivitis (AC) is an inflammation of the conjunctiva secondary to
      an immune response to exogenous antigens, usually called allergens. In fact, AC
      is a syndrome that involves the entire ocular surface, including conjunctiva,
      lids, cornea, and tear film. The signs and symptoms of AC have a meaningful
      effect on comfort and patient health, and could be influenced by environment,
      genetics and immune regulation mechanisms, all of which work together in a
      complex immunological homeostasis. Dysregulation in such immune responses could
      turn into a variety of ocular allergic diseases (OAD). This review describes some
      of the current understanding of cellular and molecular pathways involved in
      different OAD. 

PMID- 24912911
TI  - [ARIA (Allergic Rhinitis and its Impact on Asthma). Achievements in 10 years and
      future needs in Latin America].
AB  - Allergic rhinitis and asthma represent global problems of public health affecting
      all age groups; asthma and allergic rhinitis frequently coexist in the same
      patients. In Latin American prevalence of allergic rhinitis, although variable,
      is very high. Allergic rhinitis and its Impact on Asthma (ARIA) started during a
      workshop of the World Health Organization performed in 1999 and was published in
      2001. ARIA proposed a new classification of allergic rhinitis in intermittent or
      persistent and mild or moderate-severe. This approach of classification reflects
      more nearly the impact of allergic rhinitis in patients. In its review of 2010
      ARIA developed guidelines for diagnosis and treatment of allergic rhinitis and of
      clinical practices for management of comorbidities of allergic rhinitis and
      asthma based on GRADE (Grading of Recommendations, Development and Evaluation).
      ARIA has been spread and implemented in more than 50 countries. In Latin American
      an intense activity has been developed to spread these recommendations in almost
      all the countries of the region and it is important to record the obtained goals
      in the diffusion and implementation of ARIA, as well as to identify the
      unsatisfied needs from the clinical, research and implementation points of view.
      Final objective is to reinforce the priority that allergy and asthma should have,
      especially in children, in the programs of public health, as they have been
      prioritized in European Union in 2011. 

PMID- 24912912
TI  - [Hypereosinophilic syndrome as paraneoplastic presentation in an adolescent].
AB  - Hypereosinophilic syndrome is characterized by peripheral eosinophilia over 1,500
      cell/mm3 and/or tissue eosinophilia, with dysfunction or damage to organ, once
      other causes were ruled out. This paper presents a case of hypereosinophilic
      syndrome (HS) which presented as lymphoblastic leukemia in a teenager. This is a
      13 year old female, with B cell lymphoblastic leukemia at 9 years old, who
      received chemotherapy for 2 years achieving remission. One year after remission
      she presented malar rash, hair loss, arthralgias, conjuntival redness, dyspnea
      and thoracic oppression. The initial blood count only showed hypereosinophilia,
      and a bone marrow biopsy did not show blasts and had a negative
      immunophenotyping. Autoantibodies were negative, except for ANA (1:1,280 in one
      determination after one negative), complement was normal, lupic band in skin was
      negative for complement and immunoglobulins; serum IgG 2,195 mg/dL, IgA 231, IgM
      327, IgE 109 U/mL; skin testing for aeroallergens and food allergens were
      negative. Prednisone was started at 1 mg/kg. Abdominal ultrasound only reported
      biliary sludge flow and hepatosplenomegaly; chest tomography showed
      centrolobullar interstitial pattern, suggesting eosinophilic pneumonitis. The
      patient started with a generalized dermatosis, and a biopsy reported
      leucocytoclastic vasculitis. Six months after the onset of symptomatology there
      were generalized malaise, uncontrolled fever, gingival haemorrhage, asthenia and
      adynamia; a blood cell count reported blasts, and bone marrow smear confirmed the
      diagnosis of cell B lymphoblastic leukemia. The patient deteriorated rapidly
      showing signs of respiratory difficulty and acute pulmonary edema, therefore
      chemotherapy was started without response, and finally the patient died. There
      are several causes of HS, yet one of the least frequent presentations in
      childhood is the association with neoplasms. 

PMID- 24912913
TI  - Identification of process measures to reduce postoperative readmission.
AB  - BACKGROUND: Readmission rates after intestinal surgery have been notably high,
      ranging from 10 % for elective surgery to 21 % for urgent/emergent surgery. Other
      than adherence to established strategies for decreasing individual postoperative
      complications, there is little guidance available for providers to work toward
      reducing their postoperative readmission rates. STUDY DESIGN: Processes of care
      that may affect postoperative readmissions were identified through a systematic
      literature review, assessment of existing guidelines, and semi-structured
      interviews with individuals who have expertise in hospital readmissions and
      surgical quality improvement. Eleven experts ranked potential process measures
      for validity on the basis of the RAND/University of California, Los Angeles
      Appropriateness Methodology. RESULTS: Of 49 proposed process measures, 34 (69 %)
      were rated as valid. Of the 34 valid measures, two measures addressed care in the
      preoperative period. These included evaluation of patient's comorbidities,
      providing written instruction detailing the anticipated perioperative course, and
      communication with the patient's referring or primary care doctor. A measure
      addressing perioperative care stated that institutions should have a standardized
      perioperative care protocol. Additional measures focused on discharge
      instructions and communication. CONCLUSIONS: An expert panel identified several
      aspects of care that are considered essential to quality patient care and
      important to reducing postoperative readmissions.

PMID- 24912914
TI  - Perioperative nonselective non-steroidal anti-inflammatory drugs are not
      associated with anastomotic leakage after colorectal surgery.
AB  - INTRODUCTION: Recent evidence raises concern about the use of perioperative non
      steroidal anti-inflammatory drug (NSAID) use after colorectal resection. The
      purpose of this retrospective cohort study was to investigate the relationship
      between perioperative ketorolac use and anastomotic leakage after colorectal
      surgery. METHODS: A retrospective review (2004-2011) was performed on patients
      who underwent elective colorectal surgery. Univariate analysis and multivariate
      logistic regression were used to evaluate the association between patients who
      did not receive any NSAIDs and those who received ketorolac within the first 5
      days perioperatively and leak rate. RESULTS: A total of 731 patients were
      identified as having resection with primary anastomosis: 376 (51.4 %) received no
      NSAIDs and 355 (48.6 %) received ketorolac perioperatively within 5 days after
      their surgery. There were 24 (3.3 %) leaks, with 12 in both the no NSAIDs (3.2 %)
      and ketorolac (3.4 %) groups, odds ratio (OR) 1.06 (0.43, 2.62; p = 0.886).
      Adjusting for smoking, steroid use, and age, there remained no significant
      difference between ketorolac use and leakage, OR 1.21 (0.52, 2.84; p = 0.660). In
      our multivariate model, only smoking was a significant predictor of postoperative
      leak, OR 3.34 (1.30, 8.62; p = 0.021). CONCLUSIONS: There does not appear to be a
      significant association between perioperative ketorolac use and anastomotic
      leakage after colorectal surgery. However, further prospective studies are needed
      to confirm our findings before definitive guidelines on NSAID use perioperatively
      can be recommended.

PMID- 24912915
TI  - A multi-institutional analysis of open versus minimally-invasive surgery for
      gastric adenocarcinoma: results of the US gastric cancer collaborative.
AB  - BACKGROUND: Surgical experience with minimally invasive surgery (MIS) has
      increased; however, published reports on MIS resection of gastric adenocarcinoma
      are limited. METHODS: Between 2000 and 2012, 880 patients who underwent surgical
      resection of gastric adenocarcinoma were identified from a multi-institutional
      database. Clinicopathological characteristics, operative details, and outcomes
      were stratified by operative approach (open vs. MIS) and analyzed. RESULTS:
      Overall, 70 (8 %) patients had a MIS approach. Patients who underwent a MIS
      resection were more likely to have a smaller tumor (open 4.5 cm vs. MIS 3.0 cm, p
      < 0.001). MIS resections were associated with lower estimated blood loss (open
      250 cc vs. MIS 150 cc) and longer operative time (open 232 min vs. MIS 271 min)
      compared with open surgery (both p < 0.05). An R0 resection was achieved in most
      patients (open 90.9 % vs. MIS 98.6 %, p = 0.03) and median lymph node yield was
      good in both groups (open 17 vs. MIS 14, p = 0.10). MIS had a similar incidence
      of complications (open 33.1 % vs. MIS 20 %, p = 0.07) and a similar length of
      stay (open 9 days vs. MIS 7 days, p = 0.13) compared with open surgery. In the
      propensity-matched analysis, median recurrence-free and overall were not impacted
      by operative approach. CONCLUSION: An MIS approach to gastric cancer was
      associated with adequate lymph node retrieval, a high incidence of R0 resection,
      and comparable long-term oncological outcomes versus open gastrectomy.

PMID- 24912916
TI  - NSAID use and anastomotic leaks following elective colorectal surgery: a matched
      case-control study.
AB  - INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) decrease
      postoperative pain and opioid consumption. The objective of the study was to
      determine if postoperative NSAIDs were associated with anastomotic leaks
      following elective colorectal surgery. MATERIALS AND METHODS: We used a matched
      nested case-control study design. Using a prospectively collected database, we
      identified all patients having elective colorectal surgery between January 2001
      and June 2012. Cases and matched controls were identified based on the occurrence
      of a postoperative anastomotic leak. The primary and secondary exposure variables
      were, respectively, use of any NSAID and use of ketorolac specifically.
      Conditional logistic regression was used to determine the unadjusted and adjusted
      odds ratio. RESULTS: A total of 262 patients were included (65.6 % inflammatory
      bowel disease, 34.4 % cancer). Use of any NSAID was associated with a non
      significant increase in anastomotic leaks (odds ratio (OR) 1.81, 95 % confidence
      interval (CI) 0.98-3.37, p = 0.06). Use of ketorolac was associated with a
      significant increase in anastomotic leaks (OR 2.09, 95 % CI 1.12-3.89, p =
      0.021). There was no significant association between anastomotic leaks and
      cumulative NSAID dose. CONCLUSION: These data suggest that there may be an
      association between NSAIDs and risk of anastomotic leaks after colorectal
      surgery. Further research is needed to better elucidate this relationship to
      clarify the implications for patients.

PMID- 24912917
TI  - Transplantation and inflammation: implications for the modification of chemokine
      function.
AB  - Oxidative stress is a major and recurring cause of damage during inflammation,
      especially following organ transplantation. Initial ischaemia-reperfusion injury
      causes the production of many reactive oxygen and nitrogen species, and
      subsequent recruitment and activation of inflammatory cells can lead to further
      oxidative stress. This stress is well known to cause damage at the cellular
      level, for example by induction of senescence leading to the production of a
      characteristic senescence-associated secretory phenotype. Chemokines are an
      important component of the senescence-associated secretory phenotype, recruiting
      further leucocytes and reinforcing the stress and senescence responses. As well
      as inducing the production of proteins, including chemokines, oxidative stress
      can alter proteins themselves, both directly and by induction of enzymes capable
      of modification. These alterations can lead to important modifications to their
      biological activity and also alter detection by some antibodies, potentially
      limiting the biological relevance of some immunochemical and proteomic
      biomarkers. Peroxynitrite, a reactive nitrogen species generated during
      inflammation and ischaemia, can cause such modifications by nitrating chemokines.
      Matrix metalloproteinases, released by many stressed cells, can cleave
      chemokines, altering function, while peptidylarginine deiminases can inactivate
      certain chemokines by citrullination. This review discusses the relationship
      between inflammation and post-translational modification, focusing on the
      functional modulation of transplant-relevant pro-inflammatory chemokines.

PMID- 24912918
TI  - Negative regulation of DAB2IP by Akt and SCFFbw7 pathways.
AB  - Deletion of ovarian carcinoma 2/disabled homolog 2 (DOC-2/DAB2) interacting
      protein (DAB2IP), is a tumor suppressor that serves as a scaffold protein
      involved in coordinately regulating cell proliferation, survival and apoptotic
      pathways. DAB2IP is epigenetically down-regulated in a variety of tumors through
      the action of the histone methyltransferase EZH2. Although DAB2IP is
      transcriptionally down-regulated in a variety of tumors, it remains unclear if
      other mechanisms contribute to functional inactivation of DAB2IP. Here we
      demonstrate that DAB2IP can be functionally down-regulated by two independent
      mechanisms. First, we identified that Akt1 can phosphorylate DAB2IP on S847,
      which regulates the interaction between DAB2IP and its effector molecules H-Ras
      and TRAF2. Second, we demonstrated that DAB2IP can be degraded in part through
      ubiquitin-proteasome pathway by SCF(Fbw7). DAB2IP harbors two Fbw7 phosho-degron
      motifs, which can be regulated by the kinase, CK1delta. Our data hence indicate
      that in addition to epigenetic down-regulation, two additional pathways can
      functional inactivate DAB2IP. Given that DAB2IP has previously been identified to
      possess direct causal role in tumorigenesis and metastasis, our data indicate
      that a variety of pathways may pass through DAB2IP to govern cancer development,
      and therefore highlight DAB2IP agonists as potential therapeutic approaches for
      future anti-cancer drug development.

PMID- 24912919
TI  - Insecticide-treated clothes for the control of vector-borne diseases: a review on
      effectiveness and safety.
AB  - Insecticide-treated clothing has been used for many years by the military and in
      recreational activities as personal protection against bites from a variety of
      arthropods including ticks, chigger mites, sandflies and mosquitoes. Permethrin
      is the most commonly used active ingredient, but others, including bifenthrin,
      deltamethrin, cyfluthrin, DEET (N,N-diethyl-3-methylbenz-amide) and KBR3023, have
      also been trialled. Treatment is usually carried out by home or factory dipping.
      However, new microencapsulation technologies which may prolong the activity of
      insecticides on clothing are now available and may help to overcome the
      inevitable reduction in efficacy over time that occurs as a result of washing,
      ultraviolet light exposure, and the normal wear and tear of the fabric. The aim
      of this article is to review the evidence base for the use of insecticide-treated
      clothing for protection against bites from arthropods and its effect on arthropod
      borne pathogen transmission. Although some studies do demonstrate protection
      against pathogen transmission, there are surprisingly few, and the level of
      protection provided varies according to the disease and the type of study
      conducted. For example, insecticide-treated clothing has been reported to give
      between 0% and 75% protection against malaria and between 0% and 79% protection
      against leishmaniasis. Studies vary in the type of treatment used, the age group
      of participants, the geographical location of the study, and the pathogen
      transmission potential. This makes it difficult to compare and assess
      intervention trials. Overall, there is substantial evidence that insecticide
      treated clothing can provide protection against arthropod bites. Bite protection
      evidence suggests that insecticide-treated clothing may be useful in the
      prevention of pathogen transmission, but further investigations are required to
      accurately demonstrate transmission reduction. 

PMID- 24912920
TI  - HMCN1, a cell polarity-related gene, is somatically mutated in gastric and
      colorectal cancers.

PMID- 24912921
TI  - Proven value of translational research with appropriate animal models to advance
      breast cancer treatment and save lives: the tamoxifen tale.

PMID- 24912922
TI  - Properties of poly(lactide)-whey protein isolate laminated films.
AB  - BACKGROUND: This study aims to examine the feasibility of a novel multi-layer
      barrier film made entirely from biopolymers, which can be disposed after use in
      an economically and ecologically acceptable way, by employing mechanical strength
      and moisture barrier of poly(lactide) (PLA) films and oxygen barrier enhancement
      of whey protein isolate (WPI) films. The effect of glycerol was also determined.
      The three-layer films, PLA/WPI/PLA, were compared with those made of linear low
      density polyethylene films (LLDPE/WPI/LLDPE). Composite structures of three-layer
      films obtained by a simple casting method using denatured WPI solution
      plasticised with glycerol (GLY) at three different ratios of GLY:WPI (1:4, 1:2.5
      and 1:1.5). The WPI solution was applied between two base layers of corona
      treated PLA or LLDPE films. RESULT: The multi-layer films showed good appearance
      with no noticeably visible change and good adhesion of layers. PLA enhanced
      tensile strength of the composite structure. Oxygen permeability of the multi
      layer films was significantly lower than the base films. The water vapour
      permeability of the structure relied mainly on the base films. The plasticiser
      content did not significantly affect the properties of the multi-layer
      structures. CONCLUSION: Results suggested that WPI could work successfully as an
      alternative oxygen barrier layer of multi-layer structures.

PMID- 24912924
TI  - Reduction in accuracy of genomic prediction for ordered categorical data compared
      to continuous observations.
AB  - BACKGROUND: Accuracy of genomic prediction depends on number of records in the
      training population, heritability, effective population size, genetic
      architecture, and relatedness of training and validation populations. Many traits
      have ordered categories including reproductive performance and susceptibility or
      resistance to disease. Categorical scores are often recorded because they are
      easier to obtain than continuous observations. Bayesian linear regression has
      been extended to the threshold model for genomic prediction. The objective of
      this study was to quantify reductions in accuracy for ordinal categorical traits
      relative to continuous traits. METHODS: Efficiency of genomic prediction was
      evaluated for heritabilities of 0.10, 0.25 or 0.50. Phenotypes were simulated for
      2250 purebred animals using 50 QTL selected from actual 50k SNP (single
      nucleotide polymorphism) genotypes giving a proportion of causal to total loci
      of.0001. A Bayes C pi threshold model simultaneously fitted all 50k markers
      except those that represented QTL. Estimated SNP effects were utilized to predict
      genomic breeding values in purebred (n = 239) or multibreed (n = 924) validation
      populations. Correlations between true and predicted genomic merit in validation
      populations were used to assess predictive ability. RESULTS: Accuracies of
      genomic estimated breeding values ranged from 0.12 to 0.66 for purebred and from
      0.04 to 0.53 for multibreed validation populations based on Bayes C pi linear
      model analysis of the simulated underlying variable. Accuracies for ordinal
      categorical scores analyzed by the Bayes C pi threshold model were 20% to 50%
      lower and ranged from 0.04 to 0.55 for purebred and from 0.01 to 0.44 for
      multibreed validation populations. Analysis of ordinal categorical scores using a
      linear model resulted in further reductions in accuracy. CONCLUSIONS: Threshold
      traits result in markedly lower accuracy than a linear model on the underlying
      variable. To achieve an accuracy equal or greater than for continuous phenotypes
      with a training population of 1000 animals, a 2.25 fold increase in training
      population size was required for categorical scores fitted with the threshold
      model. The threshold model resulted in higher accuracies than the linear model
      and its advantage was greatest when training populations were smallest.

PMID- 24912926
TI  - CME update: review articles and commentaries in JMRI.

PMID- 24912925
TI  - Microparticles and sudden cardiac death due to coronary occlusion. The TIDE
      (Thrombus and Inflammation in sudden DEath) study.
AB  - AIMS: The pattern of coronary occlusion might contribute to the onset of
      ventricular arrhythmia and sudden cardiac death (SCD). We hypothesized that the
      concentrations of microparticles might differ between SCD and ST-elevation
      myocardial infarction (STEMI) patients without rhythmic disturbances. METHODS AND
      RESULTS: The study sample includes consecutive patients hospitalized in two
      French tertiary centres between 2006 and 2011 for SCD with angiographically
      proven acute coronary occlusion (n=23), for STEMI (n=61) and for a planned
      percutaneous coronary angioplasty (PCI) (n=35, controls). During PCI blood was
      collected in the arch of aorta (systemic blood) before and after the procedure
      and in the culprit coronary lesion with an aspiration catheter. Microparticles
      were analysed by flow cytometry in a blinded manner to quantify endothelial
      (CD144+), platelet (CD41+), leucocyte (CD11a+) and erythrocyte (CD235a+) derived
      microparticles. After multivariate analysis, intracoronary concentrations of
      endothelial-derived microparticles were significantly higher in SCD than in STEMI
      patients (129 (74-185) vs. 50 (21-118) nb/ul; p < 0.01). Intracoronary and
      systemic blood concentrations of platelet-derived microparticles were not
      different between SCD and controls, suggesting limited impact of cardiac massage
      and electric defibrillation in microparticle concentrations. CONCLUSION: The
      higher concentrations of endothelial-derived microparticles in SCD due to acute
      coronary occlusion compared with STEMI without rhythmic disturbances suggests
      different patterns of acute coronary occlusion.

PMID- 24912923
TI  - A review of malaria transmission dynamics in forest ecosystems.
AB  - Malaria continues to be a major health problem in more than 100 endemic countries
      located primarily in tropical and sub-tropical regions around the world. Malaria
      transmission is a dynamic process and involves many interlinked factors, from
      uncontrollable natural environmental conditions to man-made disturbances to
      nature. Almost half of the population at risk of malaria lives in forest areas.
      Forests are hot beds of malaria transmission as they provide conditions such as
      vegetation cover, temperature, rainfall and humidity conditions that are
      conducive to distribution and survival of malaria vectors. Forests often lack
      infrastructure and harbor tribes with distinct genetic traits, socio-cultural
      beliefs and practices that greatly influence malaria transmission dynamics. Here
      we summarize the various topographical, entomological, parasitological, human
      ecological and socio-economic factors, which are crucial and shape malaria
      transmission in forested areas. An in-depth understanding and synthesis of the
      intricate relationship of these parameters in achieving better malaria control in
      various types of forest ecosystems is emphasized. 

PMID- 24912927
TI  - [Promotion of research and innovation: a commitment to training].

PMID- 24912928
TI  - Localization of phytase transcripts in germinating seeds of the common bean
      (Phaseolus vulgaris L.).
AB  - MAIN CONCLUSION: The work provides the first-time evidence of tissue-specific
      expression of a phytase gene in the germinating seeds of Phaseolus vulgaris.
      Phytase enzyme plays a major role in germinating seeds. It is also active during
      N2 fixation within nodules of legumes. The effect of phosphorus (P) deficiency on
      phytase gene expression and localization in N2-fixing root nodules has been
      recently studied in hydroaeroponic culture of Phaseolus vulgaris. In this study,
      phytase gene transcripts within the germinating seed tissues of the P-inefficient
      P. vulgaris recombinant inbred line RIL147 were in situ localized with a similar
      RT-PCR recipe as that used for nodules. Our results show that the phytase gene
      expression was mainly localized in the outer layers, vascular cells and
      parenchyma of germinating seeds whereas it was localized in the inner and middle
      cortex of nodules. Image analysis quantified higher fluorescence intensity of the
      phytase transcript signal in the seed embryo than in radicles, cotyledons or the
      nodule cortex. Furthermore, the phytase activity was 22-fold higher in cotyledons
      (43 nmol min(-1) g(-1) dry weight) than in nodules (2 nmol min(-1) g(-1) dry
      weight). The K m and V m values of phytase activity in cotyledons were also
      significantly higher than in nodules. Interestingly, the amplified sequence of
      cDNA phytase exhibited highest homology with the Glycine max purple acid
      phosphatase (NM_001289274) 90 % for germinating seed as compared to nodule
      phytase cDNA displaying 94 % homology with the Glycine max phytase (GQ422774.1).
      It is concluded that phytase enzymes are likely to vary from seeds to nodules and
      that phytase enzymes play key roles in the use of organic P or N2 fixation, as it
      is well known for germination.

PMID- 24912929
TI  - Effects of high summer temperatures on mortality in 50 Spanish cities.
AB  - BACKGROUND: Periods of high temperature have been widely found to be associated
      with excess mortality but with variable relationships in different cities. How
      these specifics depend on climatic and other characteristics of cities is not
      well understood. We assess summer temperature-mortality relationships using data
      from 50 provincial capitals in Spain, during the period 1990-2004. METHODS:
      Poisson time series regression analyses were applied to daily temperature and
      mortality data, adjusting for potential confounding seasonal factors.
      Associations of heat with mortality were summarised for each city as the risk
      increments at the 99th compared to the 90th percentiles of the whole-year
      temperature distributions, as predicted from spline curves. RESULTS: Risk
      increments averaged 14.6% between both centiles, or 3.3% per 1 Celsius degree.
      Although risk increments varied substantially between cities, the range of
      temperature from the 90th to 99th centile was the only characteristic
      independently significantly associated with them. The heat increment did not
      depend on other city climatic, socio-demographic and geographic determinants.
      CONCLUSIONS: Cities in Spain are partially adapted to high mean summer
      temperatures but not to high variation in summer temperatures.

PMID- 24912931
TI  - Possible ways of reducing dental erosive potential of acidic beverages.
AB  - Frequent consumption of acidic beverages is related to excessive tooth wear,
      namely dental erosion. Preventive measures may involve reduction or elimination
      of acidic drink consumption. However, the success of this approach is difficult
      to achieve as it is highly dependent on patient compliance. Therefore, a
      practical way of minimizing the erosive potential of popular acidic drinks may be
      their chemical modification. The aim of this article was to review the different
      methods of modification and their shortcomings. The available literature
      demonstrates that the erosive potential of most acidic beverages could be
      reduced. To date, the effectiveness of soluble calcium salts supplementation is
      the best established. However, modification can reduce the sensorial quality of
      the drink and shorten its shelf-life. There is also a need to evaluate the lowest
      effective and safe dose of the additive. 

PMID- 24912930
TI  - Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced
      kindling and associated cognitive impairment in rats.
AB  - Numerous studies have demonstrated the antioxidant effects of grape seed
      proanthocyanidin extract (GSPE). The generation of free radicals and the ensuing
      apoptosis may contribute to the pathogenesis of epilepsy; therefore, in the
      present study, we examined the effects of GSPE on cognitive impairment and
      neuronal damage induced by chronic seizures in rats. Seizures were induced by a
      daily intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ; 35 mg/kg/day,
      36 days). Two other groups were treated with GSPE (100 or 200 mg/kg/day, orally)
      for 24 days and then for 36 days prior to each PTZ injection. After the final PTZ
      injection, hippocampus-dependent spatial learning was assessed using the Morris
      water maze (MWM). The rats were then sacrificed for the measurement of
      hippocampal malondialdehyde (MDA, a measure of lipid peroxidation) and
      glutathione (GSH, a measure of endogenous antioxidant capacity) levels, and for
      the expression of pro-apoptotic factors [cytochrome c (Cyt c), caspase-9 and
      caspase-3]. The mitochondrial generation of reactive oxygen species (ROS), degree
      of mitochondrial swelling, neuronal damage and mitochondrial ultrastructure were
      also examined. Performance in the MWM was markedly impaired by PTZ-induced
      seizures, as evidenced by longer escape latencies during training and fewer
      platform crossings during the probe trial. This cognitive decline was accompanied
      by oxidative stress (MDA accumulation, ROS generation, reduced GSH activity), an
      increased expression of pro-apoptotic proteins, as well as damage to CA1
      pyramidal neurons and the mitochondria. Pre-treatment with GSPE dose-dependently
      reversed PTZ-induced impaired performance in the MWM, oxidative stress,
      mitochondrial ROS generation, the expression of pro-apoptotic proteins and
      neuronal and mitochondrial damage. Thus, GSPE may reverse the hippocampal
      dysfunction induced by chronic seizures, by reducing oxidative stress and
      preserving mitochondrial function.

PMID- 24912932
TI  - Editorial Comment to Modified penile disassembly technique for boys with
      epispadias and those undergoing complete primary repair of exstrophy: long-term
      outcomes.

PMID- 24912933
TI  - Peritonsillar abscess with rapid progression to complete airway obstruction in a
      toddler.
AB  - Peritonsillar abscess in children younger than 5 years old has rarely been
      reported in the literature. We present the case of a 22-month-old child with a
      right peritonsillar abscess with parapharyngeal spread that was complicated by
      airway obstruction secondary to rapid epiglottic swelling. The severity of the
      airway obstruction necessitated an urgent tracheostomy, incision and drainage of
      the peritonsillar abscess and right lateral pharyngeal space, and a right
      tonsillectomy. Here we report the case and review the literature regarding
      peritonsillar space infections, their potential complications, and treatment.

PMID- 24912934
TI  - 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone exhibits a potent
      radiosensitizing effect with induced oncosis in human nasopharyngeal carcinoma
      cells.
AB  - 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone (DAMA) was synthesized from
      emodin. In the present study, the activity and the oncosis-like mechanism of DAMA
      enhanced nasopharyngeal carcinoma (NPC) cell sensitivity to ionizing radiation
      was examined. The results demonstrated that DAMA has a 1.46-fold
      radiosensitisation activity for nasopharyngeal carcinoma CNE 1 cells with a non
      cytotoxic concentration of 10 ug/ml DAMA combined with 2 Gy. Following treatment
      of DAMA combined with radiation, CNE-1 cells revealed severe cytoplasmic swelling
      and vacuolization, swollen mitochondria and dilation of the nuclei without
      chromatin condensation, yielding a typical morphology of oncosis. Oncosis-related
      gene expression of ATP synthase F0 subunit 6, chromatin modifying protein 6 and
      cyclophilin D mRNA increased significantly in the 8 Gy radiation group and the 2
      Gy radiation combined with DAMA group. A significant decrease of ATP synthase
      protein 8 mRNA was observed and the levels of intracellular ATP were also
      reduced. In addition, the levels of intracellular Ca2+ were increased. In
      conclusion, DAMA is a potent radiation sensitizer in nasopharyngeal carcinoma
      cells and mediates its radiosensitisation via oncosis. 

PMID- 24912935
TI  - Acute retinal periphlebitis mimicking frosted branch angiitis associated with
      exudative retinal detachment after blunt eye trauma.
AB  - We report a case of a 14-year-old otherwise healthy patient who developed acute
      retinal periphlebitis mimicking frosted branch angiitis inferotemporally and
      associated exudative retinal detachment in the left eye following blunt trauma.
      Fluorescein angiography revealed delayed filling of inferotemporal branch retinal
      vein and late leakage of sheathed retinal venules, and late pooling in the area
      of exudative retinal detachment. Indocyanine green angiography showed a crescent
      shaped hypofluorescent streak concentric to the optic disk inferiorly highly
      suggestive of choroidal rupture. The patient was treated with oral prednisone,
      with gradual tapering over a period of 15 days. One month after presentation,
      retinal vein sheathing and exudative retinal detachment had resolved, with the
      development of peripapillary subretinal fibrosis, macular atrophy, pseudomacular
      hole, and epiretinal membrane. The acute perivenular sheathing in our patient
      might be related to autoimmune-mediated reaction induced by retinal vascular
      damage caused by severe ocular trauma. Fluorescein angiography and indocyanine
      green angiography findings might suggest that the retinal detachment could be
      caused by leakage from choroid through Bruch's membrane and retinal pigment
      epithelium rupture or by transient dysfunction of the outer or inner blood
      retinal barrier.

PMID- 24912936
TI  - The modulatory role of alpha-melanocyte stimulating hormone administered spinally
      in the regulation of blood glucose level in d-glucose-fed and restraint stress
      mouse models.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) is known as a regulator of the
      blood glucose homeostasis and food intake. In the present study, the possible
      roles of alpha-MSH located in the spinal cord in the regulation of the blood
      glucose level were investigated in d-glucose-fed and immobilization stress (IMO)
      mouse models. We found in the present study that intrathecal (i.t.) injection
      with alpha-MSH alone did not affect the blood glucose level. However, i.t.
      administration with alpha-MSH reduced the blood glucose level in d-glucose-fed
      model. The plasma insulin level was increased in d-glucose-fed model and was
      further increased by alpha-MSH, whereas alpha-MSH did not affect plasma
      corticosterone level in d-glucose-fed model. In addition, i.t. administration
      with glucagon alone enhanced blood glucose level and, i.t. injection with
      glucagon also increased the blood glucose level in d-glucose-fed model. In
      contrasted to results observed in d-glucose-fed model, i.t. treatment with alpha
      MSH caused enhancement of the blood glucose level in IMO model. The plasma
      insulin level was increased in IMO model. The increased plasma insulin level by
      IMO was reduced by i.t. treatment with alpha-MSH, whereas i.t. pretreatment with
      alpha-MSH did not affect plasma corticosterone level in IMO model. Taken
      together, although spinally located alpha-MSH itself does not alter the blood
      glucose level, our results suggest that the activation of alpha-MSH system
      located in the spinal cord play important modulatory roles for the reduction of
      the blood glucose level in d-glucose fed model whereas alpha-MSH is responsible
      for the up-regulation of the blood glucose level in IMO model. The enhancement of
      insulin release may be responsible for modulatory action of alpha-MSH in down
      regulation of the blood glucose in d-glucose fed model whereas reduction of
      insulin release may be responsible for modulatory action of alpha-MSH in up
      regulation of the blood glucose in IMO model.

PMID- 24912939
TI  - NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma
      of the uterine cervix.
AB  - BACKGROUND: NQO1 (NAD(P)H: quinone oxidoreductase-1), located on chromosome
      16q22, functions primarily to protect normal cells from oxidant stress and
      electrophilic attack. Recent studies have revealed that NQO1 is expressed at a
      high level in most human solid tumors including those of the colon, breast,
      pancreas, ovaries and thyroid, and it has also been detected following the
      induction of cell cycle progression and proliferation of melanoma cells. In this
      study, we aimed to investigate the clinicopathological significance of
      upregulated NQO1 protein expression in squamous cell carcinomas (SCCs) of the
      uterine cervix. METHODS: The localization of the NQO1 protein was determined in
      the SiHa cervical squamous cancer cell line using immunofluorescence (IF)
      staining, and immunohistochemical (IHC) staining performed on paraffin-embedded
      cervical SCC specimens from 177 patients. For comparison, 94 cervical
      intraepithelial neoplasia (CIN) and 25 normal cervical epithelia samples were
      also included. QRT-PCR was performed on RNA from fresh tissues to detect NQO1
      mRNA expression levels, and HPV infection status was genotyped using
      oligonucleotide microarray. Disease-free survival (DFS) and 5-year overall
      survival (OS) rates for all cervical SCC patients were calculated using the
      Kaplan-Meier method, and univariate and multivariate analysis was performed using
      the Cox proportional hazards regression model. RESULTS: The NQO1 protein showed a
      mainly cytoplasmic staining pattern in cervical cancer cells, and only three
      cases of cervical SCC showed a nuclear staining pattern. The strongly positive
      rate of NQO1 protein expression was significantly higher in cervical SCCs and
      CINs than in normal cervical epithelia. High-level NQO1 expression was closely
      associated with poor differentiation, late-stage, lymph node metastasis and high
      risk for HPV infection. Additionally, high-level NQO1 expression was associated
      with lower DFS and 5-year OS rates, particularly for patients with early-stage
      cervical SCCs. Furthermore, Cox analysis revealed that NQO1 expression emerged as
      a significant independent hazard factor for DFS rate in patients with cervical
      SCC. CONCLUSIONS: NQO1 overexpression might be an independent biomarker for
      prognostic evaluation of cervical SCCs.

PMID- 24912940
TI  - Synthesis and characterization of 14C-labelled sulfate conjugates of steroid
      oestrogens.
AB  - Steroid oestrogens are typical endocrine-disrupting compounds in the environment
      and are excreted from the human and animals mainly as conjugates, including
      sulfate and glucuronide salts. The oestrogen conjugates are largely biologically
      inactive, but they can be de-conjugated and release free oestrogens, which
      usually exhibit strong oestrogenicity. Therefore, it is important to study the
      fate of oestrogen conjugates in the environment. However, because of the
      complexity of environmental matrixes, time-consuming pre-treatments of samples
      are usually required to reduce the interference of the matrixes. (14)C
      radioisotope can trace target substances and their degradation products at low
      concentrations in complex environmental samples and is therefore essential in
      such studies. We synthesized three oestrogen sulfates with (14)C-labelling at the
      ring, i.e. [3-(14)C]-estrone-3-sulfate ammonium salt, [3-(14)C]-17beta-estradiol
      17-sulfate ammonium salt, and [3-(14)C]-17beta-estradiol-3,17-disulfate
      diammonium salt with radiochemical purities of >98% by sulfation of [3-(14)C]
      labelled estrone and 17beta-estradiol in dry pyridine with SO3 -triethylamine at
      room temperature or 90-95  degrees C, followed by hydrolysis with KOH-methanol
      solution and purification by preparative thin-layer chromatography on silica gel
      using an ammonia-containing eluent. The products were characterized by mass
      spectrometry and (13)C and (1)H nuclear magnetic resonance spectroscopy, using
      their corresponding non-labelled compounds. The (14)C-labelled oestrogen
      conjugates provide possibilities for studying their fate in soil and sediment
      environments as well as in the animal manure.

PMID- 24912941
TI  - Thermosensitive block copolymer hydrogels based on poly(E-caprolactone) and
      polyethylene glycol for biomedical applications: state of the art and future
      perspectives.
AB  - This review focuses on the challenges associated with the design and development
      of injectable hydrogels of synthetic origin based on FDA approved blocks, such as
      polyethylene glycol (PEG) and poly(E-caprolactone) (PCL). An overview of recent
      studies on inverse thermosensitive PEG/PCL hydrogels is provided. These systems
      have been proposed to overcome the limitations of previously introduced
      degradable thermosensitive hydrogels [e.g., PEG/poly(lactide-co-glycolic acid)
      hydrogels]. PEG/PCL hydrogels are advantageous due to their higher gel strength,
      slower degradation rate and availability in powder form. Particularly, triblock
      PEG/PCL copolymers have been widely investigated, with PCL-PEG-PCL (PCEC)
      hydrogels showing superior gel strength and slower degradation kinetics than PEG
      PCL-PEG (PECE) hydrogels. Compared to triblock PEG/PCL copolymers, concentrated
      solutions of multiblock PEG/PCL copolymers were stable due to their slower
      crystallization rate. However, the resulting hydrogel gel strength was low.
      Inverse thermosensitive triblock PEG/PCL hydrogels have been mainly applied in
      tissue engineering, to decrease tissue adherence or, in combination with
      bioactive molecules, to promote tissue regeneration. They have also found
      application as in situ drug delivery carriers. On the other hand, the wide
      potentialities of multiblock PEG/PCL hydrogels, associated with the stability of
      their water-based solutions under storage, their higher degradation time compared
      to triblock copolymer hydrogels and the possibility to insert bioactive building
      blocks along the copolymer chains, have not been fully exploited yet. A critical
      discussion is provided to highlight advantages and limitations of currently
      developed themosensitive PEG/PCL hydrogels, suggesting future strategies for the
      realization of PEG/PCL-based copolymers with improved performance in the
      different application fields.

PMID- 24912942
TI  - A morphine-oxycodone combo pill: toward the "holy grail" for opioids or a
      justifiably rejected drug?

PMID- 24912943
TI  - Assessing systems quality in a changing health care environment: the 2009-10
      national survey of children with special health care needs.
AB  - To provide a national, population-based assessment of the quality of the health
      care system for children and youth with special health care needs using a
      framework of six health care system quality indicators. 49,242 interviews with
      parents of children with special health care needs from the 2009-10 National
      Survey of Children with Special Health Care Needs (NS-CSHCN) were examined to
      determine the extent to which CSHCN had access to six quality indicators of a
      well-functioning system of services. Criteria for determining access to each
      indicator were established and applied to the survey data to estimate the
      proportion of CSHCN meeting each quality indicator by socio-demographic status
      and functional limitations. 17.6% of CSHCN received care consistent with all six
      quality indicators. Results for each component of the system quality framework
      ranged from a high of 70.3% of parents reporting that they shared decision-making
      with healthcare providers to a low of 40% of parents reporting receipt of
      services needed for transition to adult health care. Attainment rates were lower
      for CSHCN of minority racial and ethnic groups, those residing in households
      where English was not the primary language, those in lower income households, and
      those most impacted by their health condition. Only a small proportion of CSHCN
      receive all identified attributes of a high-quality system of services. Moreover,
      significant disparities exist whereby those most impacted by their conditions and
      those in traditionally disadvantaged groups are served least well by the current
      system. A small proportion of CSHCN appear to remain essentially outside of the
      system, having met few if any of the elements studied.

PMID- 24912944
TI  - Pregnancy Risk Assessment Monitoring System in Ireland: methods and response
      rates.
AB  - To describe response rates and characteristics associated with response to the
      Pregnancy Risk Assessment Monitoring System study in Ireland (PRAMS Ireland).
      Using hospital discharge records of live births at a large, urban, obstetric
      hospital, a sampling frame of approximately 2,400 mother-infant pairs were used
      to alternately sample 1,200 women. Mothers' information including name, address,
      parity, age and infant characteristics such as sex and gestational age at
      delivery were extracted from records. Modes of contact included an invitation
      letter with option to opt out of the study, three mail surveys, a reminder letter
      and text message reminder for remaining non-respondents. Sixty-one per cent of
      women responded to the PRAMS Ireland survey over a 133 day response period. Women
      aged <30, single women, multiparous women and women with a preterm delivery were
      less likely to respond. Women participating in PRAMS Ireland were similar to the
      national birth profile in 2011 which had a mean age of 32, were 40 % primiparous,
      33 % single or never married and had a 28 % caesarean section rate. Survey and
      protocol changes are required to increase response rates above recommended
      Centers for Disease Control and Prevention (CDC) thresholds of 65 % within the
      recommended 90 day data collection cycle. Additional efforts such as
      stratification and over-sampling are required to increase representativeness
      among hard to reach groups such as younger, single and multiparous women before
      expanding the project to an ongoing, national surveillance system in Ireland.

PMID- 24912945
TI  - Exercise during pregnancy and its association with gestational weight gain.
AB  - We examined the association between exercise during pregnancy and meeting
      gestational weight gain recommendations. Data came from the 2009 South Carolina
      Pregnancy Risk Assessment Monitoring System (n = 856). Women reported their
      participation in exercise/sports activities before and during pregnancy,
      including the number of months and types of exercise. We developed an exercise
      index (EI), the product of the number of months spent in exercise and average
      metabolic equivalents for specific exercise. The 2009 Institute of Medicine's
      guideline was used to categorize gestational weight gain into three classes:
      inadequate, adequate, and excessive. Multinomial logistic regression models were
      used to adjust for confounders. Over 46 % of women exceeded the recommended
      weight gain during pregnancy. Nearly one third (31.9 %) of women reported
      exercising >=3 times a week at any time during pregnancy. Compared to women who
      did not report this level of exercise during pregnancy, exercising women were
      more likely to meet gestational weight gain recommendations (32.7 vs. 18.7 %) and
      had a lower odds of excessive gestational weight gain [adjusted odds ratio (AOR)
      0.43, 95 % confidence interval 0.24-0.78]. Women with an EI above the median
      value of those women who exercised or women who exercised >=3 times a week for 6
      9 months during pregnancy had lower odds of excessive gestational weight gain
      (AOR for EI 0.20, 0.08-0.49; AOR for months 0.26, 0.12-0.56, respectively). Our
      findings support the need to promote or increase exercise during pregnancy to
      reduce the high proportion of women who are gaining excessive weight.

PMID- 24912946
TI  - A novel thermoalkaliphilic xylanase from Gordonia sp. is salt, solvent and
      surfactant tolerant.
AB  - Two aerobic bacterial consortia namely Con T and Con R were developed by
      enrichment technique from termite gut and cow dung respectively, using xylan as a
      sole carbon source. Molecular characterization of Con R based on 16S rRNA
      sequence analysis showed the presence of Pannonibacter sp. R-3 and
      Pseudoxanthomas sp. R-5. On the other hand, Con T showed the presence of
      Pseudoxanthomas sp. T-5, Cellulosimicrobium sp. T-21, and Gordonia sp. T-30.
      Being the maximum xylanase producer among the five isolates and being a novel
      xylanase producing bacterial genus, Gordonia sp. T-30 was selected. Xylanase
      produced by Gordonia sp. T-30 showed optimum activity at 60  degrees C and pH 9.
      Xylanase was 95% stable for 120 min at pH 9.0 and 98% stable at 60  degrees C for
      90 min. Xylanase activity was stimulated in the presence of organic solvents such
      as petroleum ether, acetone, diethyl ether, n-hexane, and benzene. Detergent like
      cetyltrimethylammonium bromide and presence of NaCl also accelerated the xylanase
      function. Comparative evaluation was studied between sterilized and non
      sterilized solid fermentation to produce xylanase by Gordonia sp. T-30 using
      various agricultural residues as growth substrate in cost effective manner.
      Industrially important features endowed by this xylanase make it a very promising
      candidate for food, feed, and fuel industry. 

PMID- 24912947
TI  - Clinical application of adoptive T cell therapy in solid tumors.
AB  - As an emerging therapeutic approach, adoptive T cell therapy shown promise in
      advanced solid malignancies. The results obtained in patients with metastatic
      melanoma and kidney cancer are encouraging because of the visible clinical
      benefits and limited adverse effects. Recently, the genetically-modified T cells
      expressing specific T cell receptors or chimeric antigen receptors are just now
      entering the clinical arena and show great potential for high avidity to tumor
      associated antigens and long-lasting anti-tumor responses. However, continued
      investigations are necessary to improve the cell product quality so as to
      decrease adverse effects and clinical costs, and make adoptive T cell therapy a
      tool of choice for solid malignancies.

PMID- 24912948
TI  - Immune checkpoint blockade in hepatocellular carcinoma: current progress and
      future directions.
AB  - Immune checkpoint blockade has recently emerged as a promising therapeutic
      approach for various malignancies including hepatocellular carcinoma (HCC).
      Preclinical and clinical studies have shown the potential benefit of modulating
      the immunogenicity of HCC. In addition, recent advances in tumor immunology have
      broadened our understanding of the complex mechanism of immune evasion. In this
      review we summarize the current knowledge on HCC immunology and discuss the
      potential of immune checkpoint blockade as a novel HCC therapy from the basic,
      translational, and clinical perspectives.

PMID- 24912949
TI  - Clinical trials in a remote Aboriginal setting: lessons from the BOABS smoking
      cessation study.
AB  - BACKGROUND: There is limited evidence regarding the best approaches to helping
      Indigenous Australians to stop smoking. The composite analysis of the only two
      smoking cessation randomised controlled trials (RCTs) investigating this suggests
      that one-on-one extra support delivered by and provided to Indigenous Australians
      in a primary health care setting appears to be more effective than usual care in
      encouraging smoking cessation. This paper describes the lessons learnt from one
      of these studies, the Be Our Ally Beat Smoking (BOABS) Study, and how to develop
      and implement an integrated smoking cessation program. METHODS: Qualitative study
      using data collected from multiple documentary sources related to the BOABS
      Study. As the project neared completion the research team participated in four
      workshops to review and conduct thematic analyses of these documents. RESULTS:
      Challenges we encountered during the relatively complex BOABS Study included
      recruiting sufficient number of participants; managing the project in two distant
      locations and ensuring high quality work across both sites; providing appropriate
      training and support to Aboriginal researchers; significant staff absences, staff
      shortages and high workforce turnover; determining where and how the project
      fitted in the clinics and consequent siloing of the Aboriginal researchers
      relating to the requirements of RCTs; resistance to change, and maintaining
      organisational commitment and priority for the project. The results of this study
      also demonstrated the importance of local Aboriginal ownership, commitment,
      participation and control. This included knowledge of local communities, the
      flexibility to adapt interventions to local settings and circumstances, and
      taking sufficient time to allow this to occur. CONCLUSIONS: The keys to the
      success of the BOABS Study were local development, ownership and participation,
      worker professional development and support, and operating within a framework of
      cultural safety. There were difficulties associated with the BOABS Study being an
      RCT, and many of these are shared with stand-alone programs. Interventions
      targeted at particular health problems are best integrated with usual primary
      health care. Research to investigate complex interventions in Indigenous health
      should not be limited to randomised clinical trials and funding needs to reflect
      the additional, but necessary, cost of providing for local control of planning
      and implementation.

PMID- 24912950
TI  - Sensitivity and specificity of single-tube osmotic fragility test and its
      different methods as screening test for thalassemia trait: an alternative to
      expensive laboratory tests for resource-limited countries.
AB  - OBJECTIVE: To determine the sensitivity and specificity of single-tube osmotic
      fragility (SOFT) and its different methods as screening test for thalassemia
      trait. METHODS: A cross-sectional study was conducted at Omair Sana Foundation. A
      total of 400 participants were included in the study. Three hundred were known
      thalassemia carriers (parents with at least one child with thalassemia major),
      while 100 were healthy blood donors. SOFT was performed on all 400 participants.
      Serum iron, ferritin, and DNA tests were performed on 100 participants (donors).
      ARMS technique was used for detecting thalassemia mutations. RESULTS: Sensitivity
      and specificity of SOFT (venous method) were found to be 99.6% and 86%,
      respectively, while with EDTA method, sensitivity was 95% and specificity was
      96%. For venous and EDTA methods, positive predictive values were 95.5% and
      98.6%, respectively, while negative predictive values were 98.8% and 86.6%,
      respectively. Use of EDTA and storage had an effect on the results. Sensitivity
      of SOFT was 95% at 5 min, while it decreased to 87% with EDTA method at 240 min.
      Sensitivity of SOFT for iron deficiency anemia was found to be 14%. CONCLUSION:
      SOFT can be used as screening test for thalassemia trait in a cost-effective way.
      Moreover, we also found that SOFT should be performed on venous blood without
      adding preservatives (EDTA) that can interfere with the results.

PMID- 24912951
TI  - Lubiprostone for treatment-resistant constipation associated with clozapine use.

PMID- 24912952
TI  - External validity of first-trimester algorithms in the prediction of pre
      eclampsia disease severity.
AB  - OBJECTIVE: To compare disease features in women with pre-eclampsia between those
      who are correctly identified (true positive) and those who are missed (false
      negative) when applying first-trimester prediction algorithms for pre-eclampsia
      to a prospectively enrolled population. METHOD: Six first-trimester early
      (requiring delivery < 34 weeks' gestation) pre-eclampsia algorithms were applied
      to a prospective cohort of singleton pregnancies enrolled at first-trimester
      screening. Maternal outcomes, neonatal outcomes and severity parameters for pre
      eclampsia were compared between true-positive and false-negative predictions.
      RESULTS: Twenty of 2446 (0.8%) women developed early pre-eclampsia, with 65% of
      these developing severe features and 20% HELLP syndrome. At enrollment, true
      positive cases were more likely to be African-American and chronically
      hypertensive, while false-negative cases were more likely to be Caucasian. At
      delivery, true-positive cases were more likely to have pre-eclampsia superimposed
      on hypertension, severely elevated blood pressure and creatinine level > 1.1
      mg/dL. False-negative cases were more likely to have HELLP syndrome (all P <
      0.05). CONCLUSION: In an urban population with a high prevalence of chronic
      hypertension, patients who are correctly identified by first-trimester screening
      models are more likely to develop pre-eclampsia superimposed on chronic
      hypertension with severely elevated blood pressure and evidence of renal failure.
      In contrast, patients who are missed by these algorithms are more likely to have
      HELLP syndrome. Further research is needed to confirm these findings and the
      algorithm adjustments that may be necessary to better predict pre-eclampsia
      phenotypes.

PMID- 24912953
TI  - Visualization of a polytopic membrane protein during SecY-mediated membrane
      insertion.
AB  - The biogenesis of polytopic membrane proteins occurs co-translationally on
      ribosomes that are tightly bound to a membrane-embedded protein-conducting
      channel: the Sec-complex. The path that is followed by nascent proteins inside
      the ribosome and the Sec-complex is relatively well established; however, it is
      not clear what the fate of the N-terminal transmembrane domains (TMDs) of
      polytopic membrane proteins is when the C-terminal TMDs domains are not yet
      synthesized. Here, we present the sub-nanometer cryo-electron microscopy
      structure of an in vivo generated ribosome-SecY complex that carries a membrane
      insertion intermediate of proteorhodopsin (PR). The structure reveals a pre
      opened Sec-complex and the first two TMDs of PR already outside the SecY complex
      directly in front of its proposed lateral gate. Thus, our structure is in
      agreement with positioning of N-terminal TMDs at the periphery of SecY, and in
      addition, it provides clues for the molecular mechanism underlying membrane
      protein topogenesis. 

PMID- 24912954
TI  - Detection of Wolbachia in Dirofilaria infected dogs in Portugal.
AB  - Wolbachia pipiens, an intracellular endosymbiont bacteria of filarial nematodes,
      has been implicated in the pathogenesis of filarial diseases, in particular in
      heavy Dirofilaria spp. infections. Antibiotic therapy (doxycycline) against
      Wolbachia has been proven to be suitable adjunct therapy, prior to adulticide
      treatment of canine dirofilariosis. Despite its importance, investigation on the
      Wolbachia/Dirofilaria complex in Portugal had not been undertaken so far. This
      study reports the first detection of Wolbachia in Dirofilaria spp. infected dogs
      in the context of an ongoing epidemiological survey in central-south regions in
      the country. Wolbachia DNA was detected by PCR in 52.6% (20/38) of canine blood
      samples positive for Dirofilaria immitis based on parasitological (Knott's and
      Acid Phosphatase) and serological (Witness((r))Dirofilaria) methods. No Wolbachia
      DNA could be detected in samples from dogs with occult infections (parasite
      negative but antigen positive). The lack of Wolbachia detection in some
      microfilaremic dogs was somewhat unexpected and needs to be elucidated in further
      studies, as the presence or absence of these bacteria in association with
      microfilaria is of importance for veterinarians in the management and control of
      canine dirofilariosis. 

PMID- 24912955
TI  - Use of COI, CytB and ND5 genes for intra- and inter-specific differentiation of
      Haematobia irritans and Haematobia exigua.
AB  - A multilocus sequence analysis using mitochondria-encoded cytochrome c oxidase
      subunit I (COI), cytochrome B (CytB), NADH dehydrogenase subunit 5 (ND5); nuclear
      encoded 18S ribosomal RNA (18S) and 28S ribosomal RNA (28S) genes was performed
      to determine the levels of genetic variation between the closely related species
      Haematobia irritans Linnaeus and Haematobia exigua de Meijere. Among these five
      genes, ND5 and CytB genes were found to be more variable and informative in
      resolving the interspecific relationships of both species. In contrast, the COI
      gene was more valuable in inferring the intraspecific relationships. The
      ribosomal 18S and 28S sequences of H. irritans and H. exigua were highly
      conserved with limited intra- and inter-specific variation. Molecular evidence
      presented in this study demonstrated that both flies are genetically distinct and
      could be differentiated based on sequence analysis of mitochondrial genes. 

PMID- 24912956
TI  - Pathological and histological findings associated with the feline lungworm
      Troglostrongylus brevior.
AB  - Troglostrongylus brevior is a neglected feline lungworm species, which has been
      increasingly reported in the Mediterranean area, although scant data are
      available on the respiratory alterations it causes in cats. Therefore, we
      describe the gross and histological lesions of a 20-week old kitten that
      succumbed due to the onset of a fulminant respiratory failure. At necropsy, a
      catarrhal exudate was observed in the airways, along with nematodes in the
      trachea and bronchi. The lungs were processed for histological examination and
      serial pulmonary sections were performed. A total of 14 nematodes were collected,
      being all morphologically and molecularly identified as T. brevior. Lungworms
      were histologically localized within the bronchial lumen, surrounded by an
      eosinophilic infiltrate. The presence of T. brevior in the airways has been
      histologically documented for the first time and its life-threatening potential
      is discussed. 

PMID- 24912957
TI  - Validation of a recombinant protein indirect ELISA for the detection of specific
      antibodies against Theileria uilenbergi and Theileria luwenshuni in small
      ruminants.
AB  - An enzyme-linked immunosorbent assay (ELISA) based on a recombinant Theileria
      uilenbergi immunodominant protein (rTuIP) was validated for detection of
      antibodies in 188 positive and 198 negative reference serum samples,
      respectively. The cut-off value was determined at 32.7% with 95% and 90% accuracy
      levels by two-graphic receiver-operating characteristic (TG-ROC). The equal
      diagnostic sensitivity (Se) and specificity (Sp) were calculated to be 98.4%.
      Further validation of the repeatability with positive and negative reference
      samples indicated the reliable performance of the assay. Monitoring the antibody
      dynamics of sheep experimentally infected with Theileria luwenshuni showed the
      efficient detection of antibody response against the pathogen at the early
      infection stage and up until two months post infection. Application of this assay
      for detection of antibody in field sera from previous unknown Theileria endemic
      regions in Suizhou and Guiyang showed 17.8% and 11.6% seroprevalence,
      respectively, and presence of the pathogen was confirmed by identification of the
      18S rRNA gene in the corresponding blood of the seropositive animals. These data
      support that the rTuIP ELISA could be a useful tool to study the epidemiology of
      theileriosis caused by T. uilenbergi and/or T. luwenshuni. 

PMID- 24912958
TI  - Poor agreement between self-reported diagnosis and bone mineral density results
      in the identification of osteoporosis.
AB  - Osteoporosis is a major health concern, estimated to affect millions worldwide.
      Bone mineral density (BMD) assessment is not practical for many large-scale
      epidemiological studies resulting in the reliance of self-report methods to
      ascertain diagnostic information. The aim of the study was to assess the validity
      of self-reported diagnosis of osteoporosis in a population-based study. This
      study examined data collected from 906 men and 843 women participating in the
      Geelong Osteoporosis Study. Osteoporosis was self-reported and compared against
      results of BMD scans of the hip and spine. Validity was examined by calculating
      sensitivity, specificity, positive predictive value, negative predictive value,
      and kappa statistic. Osteoporosis was self-reported by 118 (6.7%) participants
      and identified using BMD results for 64 (3.7%) participants. Specificity and
      negative predictive value were good (95.1% and 96.0%, respectively), whereas
      sensitivity and positive predictive value were poor (35.9% and 31.4%,
      respectively). The overall level of agreement (kappa) was 0.29. The results
      changed only slightly when we included participants with osteopenia and adult
      fracture as osteoporotic. Reliance on self-report methods to ascertain
      osteoporosis status is not recommended. 

PMID- 24912959
TI  - School nurses race to the top: the pilot year of how one district's school nurses
      revised their evaluation process.
AB  - During the 2013-2014 school year, the Shaker Heights, Ohio City school district
      was mandated to change its evaluation process as part of the Race to the Top
      initiative. Although not required by the federal or state Departments of
      Education, the Shaker Heights City school district tasked all members of their
      faculty and staff, including school nurses, to change their evaluation process in
      an effort to improve students' performances and outcomes. This article chronicles
      how the Shaker Heights school nurses modified their evaluation process by
      adhering to the scopes and standards of school nursing as described by the
      American Nurses Association and National Association of School Nurses. Their
      revised evaluation tool could usefully serve as a model for school districts
      nationwide; it improves student outcomes, increases the professionalism of the
      school nurse specialty, increases administrative understanding of their role, and
      increases their accountability as independent health providers in the school. 

PMID- 24912960
TI  - Assessment of secondhand smoke exposure at school among U.S. Middle and high
      school students.
AB  - To obtain nationally representative estimates of the prevalence of secondhand
      smoke (SHS) exposure at U.S. schools, we assessed the prevalence and correlates
      of SHS exposure at school among U.S. middle and high school students using data
      from the 2011 National Youth Tobacco Survey comprising of 18,866 students spread
      across all the U.S. states. Overall prevalence of SHS exposure at school was
      25.7% (95% CI: [23.6%, 27.8%]). Multivariate logistic regression indicated that
      having >=1 smoker friends (adjusted Odds Ratio [aOR] = 2.92; p < .001); being a
      smoker (aOR = 2.75; p < .001); and being aged 13-16 years, or >=17 years (vs. 9
      12 years) significantly increased the likelihood of SHS exposure. Understanding
      the health risks of SHS exposure alone did not seem to play a significant role in
      reducing exposure (aOR = .89; p = .342). These findings show there are
      significant levels of SHS exposure among students at U.S. middle and high
      schools, and sustained multipronged efforts are needed to reduce youth SHS
      exposure. 

PMID- 24912961
TI  - Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum
      levels in rheumatoid arthritis after interleukin-6 receptor blockade.
AB  - Inflammatory/metabolic factors and imbalance of haemostasis contribute to
      cardiovascular disease risk in rheumatoid arthritis (RA). Interleukin-6 (IL-6), a
      cytokine that plays an important role in immune responses, is implicated in its
      pathogenesis. In this study, the effects of the IL-6 receptor inhibitor,
      tocilizumab, on serum adipokines and coagulation/fibrinolysis factors in RA
      patients were examined. Nineteen consecutive patients (18 women, aged 48 +/- 9
      years) received six monthly infusions of 8 mg/kg tocilizumab for moderate or
      severe RA. Disease activity/severity, as well as serum levels of chemerin apelin,
      plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), glucose, insulin
      and lipids were measured at baseline and at 1, 3 and 6 months thereafter.
      Chemerin and PAI-1 levels decreased significantly from baseline through 3 to 6
      months (from 256 +/- 79 to 174 +/- 12 and 210 +/- 85 ng/ml; from 73 +/- 27 to 56
      +/- 22 and 51 +/- 28 pg/ml, respectively). Other adipokines did not change,
      despite increases in adiposity. In multivariate models, significant independent
      associations were found between baseline chemerin with age, body mass index,
      remission of disease, HAQ-Di, CRP and PAI-1. Chemerin decrease at 6 months was
      significantly associated with PAI-1 and IL-6 changes at 6 months. Baseline PAI-1
      associated negatively with remission of disease and total cholesterol, while PAI
      1 change at 6 months associated with chemerin changes and smoking status. In
      conclusion, inhibition of IL-6 signaling in RA favorably alters chemerin and PAI
      1 levels in an interrelated manner, despite increasing adiposity. This might
      represent a dual anti-inflammatory and anti-thrombotic/fibrinolytic mechanism of
      tocilizumab that may reduce cardiovascular event risk in RA patients.

PMID- 24912962
TI  - Mean platelet volume in patients with systemic lupus erythematosus.

PMID- 24912964
TI  - Regiodivergent kinetic resolution of terminal and internal rac-aziridines with
      malonates under dinuclear Schiff base catalysis.
AB  - Regiodivergent parallel kinetic resolution of aziridines with malonates was
      achieved under dinuclear Schiff base catalysis. The regiodivergent reaction
      proceeded under catalyst-control irrespective of the substituents on the
      aziridines, and 2.5-10 mol % of a Y(OTf)3/La(OiPr)3/a dinucleating Schiff base =
      1:1:1 mixture gave versatile gamma-amino acid derivatives in 96 -> >99.5% ee. Not
      only terminal but also internal racemic aziridines reacted smoothly under
      suitably combined Lewis acid/Bronsted base catalysis. 

PMID- 24912966
TI  - Diagnosing type 1 von Willebrand disease: good for patient's health or for
      doctor's prestige?

PMID- 24912963
TI  - A novel multi-locus sequence typing (MLST) protocol for Leuconostoc lactis
      isolates from traditional dairy products in China and Mongolia.
AB  - BACKGROUND: Economically, Leuconostoc lactis is one of the most important species
      in the genus Leuconostoc. It plays an important role in the food industry
      including the production of dextrans and bacteriocins. Currently, traditional
      molecular typing approaches for characterisation of this species at the isolate
      level are either unavailable or are not sufficiently reliable for practical use.
      Multilocus sequence typing (MLST) is a robust and reliable method for
      characterising bacterial and fungal species at the molecular level. In this
      study, a novel MLST protocol was developed for 50 L. lactis isolates from
      Mongolia and China. RESULTS: Sequences from eight targeted genes (groEL, carB,
      recA, pheS, murC, pyrG, rpoB and uvrC) were obtained. Sequence analysis indicated
      20 different sequence types (STs), with 13 of them being represented by a single
      isolate. Phylogenetic analysis based on the sequences of eight MLST loci
      indicated that the isolates belonged to two major groups, A (34 isolates) and B
      (16 isolates). Linkage disequilibrium analyses indicated that recombination
      occurred at a low frequency in L. lactis, indicating a clonal population
      structure. Split-decomposition analysis indicated that intraspecies recombination
      played a role in generating genotypic diversity amongst isolates. CONCLUSIONS:
      Our results indicated that MLST is a valuable tool for typing L. lactis isolates
      that can be used for further monitoring of evolutionary changes and population
      genetics.

PMID- 24912965
TI  - The morbidity and associated risk factors of cancer in chronic liver disease
      patients with diabetes mellitus: a multicenter field survey.
AB  - BACKGROUND AND AIMS: Diabetes mellitus is associated with various cancers;
      however, little is known of the relationship between cancer and diabetes in
      chronic liver disease (CLD) patients. The aim of this study is to investigate the
      morbidity and associated factors of cancer, including the use of anti-diabetics,
      in CLD patients with diabetes. PATIENTS AND METHODS: We performed a multicenter
      survey in 2012 and 478 CLD patients with diabetes were enrolled (age 64.3 +/-
      12.1 years, female/male 187/291). A frequency analysis of cancer and antidiabetic
      use was performed. Independent factors for cancer were analyzed using logistic
      regression and decision-tree analysis. RESULTS: The morbidity of cancer was
      33.3%. Hepatocellular carcinoma (HCC) and extra-hepatic cancer were diagnosed in
      24.7 and 11.3% of enrolled patients, respectively. The frequency of antidiabetic
      use was 66.5%. Of prescribed antidiabetics, 39% were dipeptidyl-peptidase 4
      inhibitors; however, their use was not significantly associated with cancer. In
      contrast, the use of exogenous insulin (OR 2.21; 95% CI 1.16-4.21, P = 0.0165)
      and sulfonylurea (OR 2.08; 95% CI 1.05-3.97, P = 0.0353) were independently
      associated with HCC and extra-hepatic cancer, respectively. In decision-tree
      analysis, exogenous insulin and sulfonylurea were also identified as a divergence
      factor for HCC and extra-hepatic cancer, respectively. CONCLUSIONS: We found a
      high morbidity of not only HCC, but also extra-hepatic cancer in CLD patients
      with diabetes. We also showed a possible association between the use of
      antidiabetics and the morbidity of cancer. Thus, a large-scale cohort study is
      needed to establish a therapeutic strategy for diabetes to suppress
      carcinogenesis in CLD patients.

PMID- 24912968
TI  - Support for medical students with mental health problems: a conceptual model.
AB  - OBJECTIVE: Medical students experience higher prevalence of mental illness than
      age-matched controls and are less likely to access appropriate help when this
      happens. The aim of this study was to determine the range of strategies deployed
      by medical schools to support medical students with mental health concerns and to
      use this to identify distinct categories. METHODS: Websites and documents
      relating to all 32 UK medical schools were looked at, as were reports for quality
      assurance visits carried out by the General Medical Council (UK). A structured
      telephone interview was carried out with medical schools. Support services were
      examined by tracing the path that might be taken by a hypothetical student with
      mental health concerns of varying severity, seeing what was required and what was
      available at each stage. RESULTS: A range of support strategies is available to
      most medical students both from their medical school and from generic services in
      the university. Medical students will usually first contact a personal tutor or a
      senior member of faculty or be contacted by them as a result of concerns raised
      either via performance issues or by another student. While individual support
      interventions are mostly based on evidence of effectiveness, there is no unifying
      theory in terms of what constitutes effective support. To enable analysis of
      support interventions and comparison across providers, a six-stage conceptual
      model of prevention was developed. The six stages are the following: prevention,
      identification, referral, escalation, treatment, and reintegration. CONCLUSIONS:
      The staged model, derived from analysis of existing interventions, provides a
      framework for evaluation of current provision and comparison of different methods
      of delivery. Moreover, it provides a framework for future research.

PMID- 24912967
TI  - Age differences in presentation, diagnosis pathway and management of colorectal
      cancer.
AB  - BACKGROUND: The gap in survival between older and younger European cancer
      patients is getting wider. It is possible that cancer in the elderly is being
      managed or treated differently than in their younger counterparts. This study
      aims to explore age disparities with respect to the clinical characteristics of
      the tumour, diagnostic pathway and treatment of colorectal cancer patients.
      METHODS: We conducted a multicenter cross sectional study in 5 Spanish regions.
      Consecutive incident cases of CRC were identified from pathology services.
      MEASUREMENTS: From patient interviews, hospital and primary care clinical
      records, we collected data on symptoms, stage, doctors investigations, time
      duration to diagnosis/treatment, quality of care and treatment. RESULTS: 777
      symptomatic cases, 154 were older than 80 years. Stage was similar by age group.
      General symptoms were more frequent in the eldest and abdominal symptoms in the
      youngest. No differences were found regarding perception of symptom seriousness
      and symptom disclosure between age groups as no longer duration to diagnosis or
      treatment was observed in the oldest groups. In primary care, only ultrasound is
      more frequently ordered in those <65 years. Those >80 years had a significantly
      higher proportion of iron testing and abdominal XR requested in hospital. We
      observed a high resection rate independently of age but less adjuvant
      chemotherapy in Stage III colon cancer, and of radiotherapy in stage II and III
      rectal cancer as age increases. CONCLUSION: There are no relevant age disparities
      in the CRC diagnosis process with similar stage, duration to diagnosis,
      investigations and surgery. However, further improvements have to be made with
      respect to adjuvant therapy.

PMID- 24912969
TI  - Using learning through discussion in medical education settings.

PMID- 24912970
TI  - From school health to integrated health: expanding our children's public mental
      health system.
AB  - There is a substantial unmet need for mental health and substance abuse services
      in the USA. In 2009, the Institute of Medicine recommended increased early
      identification and intervention for young people with mental, emotional, and
      behavioral disorders. With the expansion of integrated models in primary care
      settings, we now have the chance to improve outcomes for young people with mental
      health conditions, just as we have by improving the early identification and
      treatment of other preventable and/or treatable conditions such as obesity,
      asthma, or HIV. This is a moment of great opportunity to fundamentally change how
      young people access mental health care in our country. Through strategic
      integration of care, we can increase access to care for those who would not seek
      out mental health services because of the stigma or inconvenience of reaching out
      to a mental health provider; we can identify those who need care earlier and
      reduce the impact of mental illness on individuals, family, and community through
      early identification and treatment; and we can purposefully embed integration
      into provider training programs for both primary care and mental health providers
      to ensure sustainability. 

PMID- 24912972
TI  - The influence of biological and environmental factors on metallothionein
      concentration in the blood.
AB  - The concentration of metallothionein (MT), a low-molecular-weight protein, is
      regulated by many factors, primarily metals (zinc, cadmium, copper), cytokines,
      glucocorticoides and free radicals. These factors are determined by such aspects
      of human biology as gender, pregnancy and age, as well as by environmental
      factors including the use of oral contraceptives and cigarette smoking, all which
      may affect MT levels in the body. The aim of this study was to investigate the
      influence of these biological and environmental factors on MT concentrations in
      erythrocyte lysate and in plasma. MT concentrations were determined by a two-step
      direct enzyme-linked immunosorbent assay. Evaluation of exposure to cigarette
      smoking was performed by checking cotinine levels in the plasma of subjects. The
      studies showed higher MT concentrations in both the erythrocyte lysate and plasma
      of women when compared to men. Furthermore, pregnancy causes an increase of MT
      concentration in plasma, while oral contraceptives cause an elevated
      concentration of MT in erythrocyte lysate. Age impacts plasma MT concentrations
      in men, whereas it does not affect concentrations of MT in erythrocyte lysate. 

PMID- 24912971
TI  - Practice patterns of carotid endarterectomy as performed by different surgical
      specialties at a single institution and the effect on perioperative stroke and
      cost of preoperative imaging.
AB  - BACKGROUND: Carotid endarterectomy (CEA) is currently performed by various
      surgical specialties with varying outcomes. This study analyzes different
      surgical practice patterns and their effect on perioperative stroke and cost.
      METHODS: This is a retrospective analysis of prospectively collected data of 1000
      consecutive CEAs performed at our institution by three different specialties:
      general surgeons (GS), cardiothoracic surgeons (CTS), and vascular surgeons (VS).
      RESULTS: VS did 474 CEAs, CTS did 404, and GS did 122. VS tended to operate more
      often on symptomatic patients than CTS and GS: 40% vs 23% and 31%, respectively
      (P < .0001). Preoperative workups were significantly different between
      specialties: duplex ultrasound (DUS) only in 66%, 30%, and 18%; DUS and computed
      tomography angiography in 27%, 35%, and 29%; and DUS and magnetic resonance
      angiography in 6%, 35%, and 52% for VS, CTS, and GS, respectively (P < .001). The
      mean preoperative carotid stenosis was not significantly different between the
      specialties. The mean heparin dosage was 5168, 7522, and 5331 units (P = .0001)
      and protamine was used in 0.2%, 19%, and 8% (P < .0001) for VS, CTS, and GS,
      respectively. VS more often used postoperative drains; however, no association
      was found between heparin dosage, protamine, and drain use and postoperative
      bleeding. Patching was used in 99%, 93%, and 76% (P < .0001) for VS, CTS, and GS,
      respectively. Bovine pericardial patches were used more often by CTS and ACUSEAL
      (Gore-Tex; W. L. Gore and Associates, Flagstaff, Ariz) patches were used more
      often by GS (P < .0001). The perioperative stroke/death rates were 1.3% for VS
      and 3.1% for CTS and GS combined (P = .055); and were 0.7% for VS and 3% for CTS
      and GS combined for asymptomatic patients (P < .034). Perioperative stroke rates
      for patients who had preoperative DUS only were 0.9% vs 3.3% for patients who had
      extra imaging (computed tomography angiography/magnetic resonance angiography; P
      = .009); and were 0.9% vs 3% for asymptomatic patients (P = .05). When applying
      hospital billing charges for preoperative imaging workups (cost of DUS only vs
      DUS and other imaging), the VS practice pattern would have saved $1180 per CEA
      over CTS and GS practice patterns; a total savings of $1,180,000 in this series.
      CONCLUSIONS: CEA practice patterns differ between specialties. Although the cost
      was higher for non-VS practices, the perioperative stroke/death rate was somewhat
      higher. Therefore, educating physicians who perform CEAs on cost-saving measures
      may be appropriate.

PMID- 24912973
TI  - Global perspectives on trace element requirements.
AB  - Trace elements are inorganic constituents of the human body present in
      concentrations less than 50mg/kg body weight. An exception is iron that is found
      in slightly higher amounts, 60 mg/kg body weight, but it is classified within
      this category due to its physiological roles. Requirements of trace elements can
      vary according to age, gender, growth, body composition, genetics, pregnancy,
      lactation, wound healing and burns, alcohol abuse, infections, and diseases
      (anemia, coronary artery, Keshan, Kashin-Beck). Additionally, interactions may
      occur with dietary factors, such as other minerals (iron versus copper), phytates
      (zinc), oxalates (iron), fiber (manganese), and polyphenolic compounds
      (molybdenum). On a global basis, requirements can vary according to soil and
      geographical location, food preparation and processing, food accessibility,
      cultural practices (geophagia) and pollution. Furthermore, global differences
      exist in body composition, ethnicity, and age of menarche.

PMID- 24912975
TI  - Clinical use of placebo treatments may undermine the trust of patients: a
      response to Gold and Lichtenberg.
AB  - There is an obvious need for a critical discussion of the concepts 'placebo' and
      'placebo effect'. In a recent paper on the use of placebos in clinical medicine,
      Gold and Lichtenberg note the conceptual difficulties but use the terminology in
      a confused way throughout their paper. In our response, we demonstrate these
      problems with a few examples from their paper. 

PMID- 24912974
TI  - Mitochondrial mutations in patients with congenital heart defects by next
      generation sequencing technology.
AB  - It has been shown that mitochondrial deoxyribo nucleic acid mutations may play an
      important role in the development of cardiomyopathy, and various types of
      cardiomyopathy can be attributed to disturbed mitochondrial oxidative energy
      metabolism. Several studies have described many mutations in mitochondrial genes
      encoding for subunits of respiratory chain complexes. Thus, recent studies
      confirm that pathologic mitochondrial deoxyribo nucleic acid mutations are a
      major reason of diseases and determining them by next-generation sequencing will
      improve our understanding of dysregulation of heart development. To analyse
      mitochondrial deoxyribo nucleic acid mutations, the entire mitochondrial
      deoxyribo nucleic acid was amplified in two overlapping polymerase chain reaction
      fragments from the cardiac tissue of the 22 patients with congenital heart
      disease, undergoing cardiac surgery. Mitochondrial deoxyribo nucleic acid was
      deep sequenced by next-generation sequencing. A total of 13 novel mitochondrial
      deoxyribo nucleic acid mutations were identified in nine patients. Of the
      patients, three have novel mutations together with reported cardiomyopathy
      mutations. In all, 65 mutations were found, and 13 of them were unreported. This
      study represents the most comprehensive mitochondrial deoxyribo nucleic acid
      mutational analysis in patients with congenital heart disease. 

PMID- 24912976
TI  - Predicting the side-chain dihedral angle distributions of nonpolar, aromatic, and
      polar amino acids using hard sphere models.
AB  - The side-chain dihedral angle distributions of all amino acids have been measured
      from myriad high-resolution protein crystal structures. However, we do not yet
      know the dominant interactions that determine these distributions. Here, we
      explore to what extent the defining features of the side-chain dihedral angle
      distributions of different amino acids can be captured by a simple physical
      model. We find that a hard-sphere model for a dipeptide mimetic that includes
      only steric interactions plus stereochemical constraints is able to recapitulate
      the key features of the back-bone dependent observed amino acid side-chain
      dihedral angle distributions of Ser, Cys, Thr, Val, Ile, Leu, Phe, Tyr, and Trp.
      We find that for certain amino acids, performing the calculations with the amino
      acid of interest in the central position of a short alpha-helical segment
      improves the match between the predicted and observed distributions. We also
      identify the atomic interactions that give rise to the differences between the
      predicted distributions for the hard-sphere model of the dipeptide and that of
      the alpha-helical segment. Finally, we point out a case where the hard-sphere
      plus stereochemical constraint model is insufficient to recapitulate the observed
      side-chain dihedral angle distribution, namely the distribution P(chi3) for Met.

PMID- 24912977
TI  - Template-assisted electrochemical growth of polypyrrole nanotubes for development
      of high sensitivity glucose biosensor.
AB  - In this paper, we report the growth of polypyrrole (PPy) nanotube arrays using
      template-assisted electrochemical polymerization to fabricate enzymatic glucose
      biosensors. The PPy nanotubes were grown on platinum-coated alumina membranes
      (AnodiscTMs). By varying the polymerization time during the potentiostatic
      electropolymerization, the size/diameter of the PPy nanotubes were controlled,
      leading to changes in the subsequent enzyme immobilization (via physical
      adsorption). Enzyme electrode thus fabricated resulted in to the optimum
      sensitivity of 18.6 mA cm(-2) M(-1), a wide range of linear operation (0.25-20
      mM) and the lowest detection limit of 0.25 mM glucose concentration for the
      biosensor with the polymerization time of 40 s. The effect of polymerization
      duration on the sensitivity has been explained on the basis of porosity and
      enzyme-loading capacity of polymerized electrodes. 

PMID- 24912978
TI  - Three-dimensional microstructural imaging of sulfur poisoning-induced degradation
      in a Ni-YSZ anode of solid oxide fuel cells.
AB  - Following exposure to ppm-level hydrogen sulfide at elevated temperatures, a
      section of a solid oxide fuel cell (SOFC) Ni-YSZ anode was examined using a
      combination of synchrotron-based x-ray nanotomography and x-ray fluorescence
      techniques. While fluorescence measurements provided elemental identification and
      coarse spatial mapping, x-ray nanotomography was used to map the detailed 3-D
      spatial distribution of Ni, YSZ, and a nickel-sulfur poisoning phase. The nickel
      sulfur layer was found to form a scale covering most of the exposed nickel
      surface, blocking most fuel reformation and hydrogen oxidation reaction sites.
      Although the exposure conditions precluded the ability to develop a detailed
      kinetic description of the nickel-sulfur phase formation, the results provide
      strong evidence of the detrimental effects of 100 ppm hydrogen sulfide on typical
      Ni-YSZ anode materials.

PMID- 24912979
TI  - The first structural and spectroscopic characterisation of a ring-opened form of
      a 2H-naphtho[1,2-b]pyran: a novel photomerocyanine.
AB  - Heating 4-methoxy-1-naphthol with a 1,1-diarylprop-2-yn-1-ol gave the 2,2-diaryl
      6-methoxy-2H-naphtho[1,2-b]pyran together with the novel merocyanine, (E)-2
      [3',3'-bis(aryl)allylidene]-4-methoxynaphthalen-1(2H)-one. Brief UV-irradiation
      of the pyran favoured the formation of the (Z)-merocyanine with longer
      irradiation and/or acidic conditions favouring the (E)-isomer. 

PMID- 24912980
TI  - Gordonia jinhuaensis sp. nov., a novel actinobacterium, isolated from a VBNC
      (viable but non-culturable) state in pharmaceutical wastewater.
AB  - A Gram-stain positive, aerobic, non-motile and rod-shaped actinobacterial strain,
      designated as ZYR 51(T), was isolated from pharmaceutical wastewater in Jinhua
      city, Zhejiang province, Eastern China. Isolation was aided by using a
      resuscitation-promoting factor, suggesting the strain was recovered from a viable
      but non-culturable state. Strain ZYR 51(T) was characterized by a polyphasic
      taxonomic approach. Growth was found to occur at 10-45  degrees C, pH 6.0-10.0
      and 0-9 % NaCl (w/v). Based on the 16S rRNA gene sequence, phylogenetic analysis
      clearly demonstrated that strain ZYR 51(T) belongs to the genus Gordonia and
      showed low level similarities (below 97 %) with all other members of this genus.
      The strain was found to possess meso-diaminopimelic acid (meso-DAP), along with
      MK-9(H2) as the predominant menaquonine. Mycolic acids were found to be present.
      C16:0 (34.9 %), 10-methyl C18:0 (30.3 %), iso-C18:0(8.2 %), and summed feature 3
      (C16:1 omega6c and/or C16:1omega7c as define by MIDI; 18.8 %) were identified as
      the major cellular fatty acids. The polar lipid profile of strain ZYR 51(T) was
      found to consist of diphosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannosides and some unknown lipids. The genomic DNA G+C
      content of strain ZYR 51(T) was determined to be 67.7 mol%. The combined
      genotypic and phenotypic data showed that the strain represents a novel species
      of the genus Gordonia, for which the name Gordonia jinhuaensis sp. nov. is
      proposed, with the type strain is ZYR 51(T) (=CGMCC 1.12827(T) = NBRL B-59111(T)
      = NBRC 110001(T)). 

PMID- 24912981
TI  - Quantity and accessibility for specific targeting of receptors in tumours.
AB  - Synaphic (ligand-directed) targeting of drugs is an important potential new
      approach to drug delivery, particularly in oncology. Considerable success with
      this approach has been achieved in the treatment of blood-borne cancers, but the
      advances with solid tumours have been modest. Here, we have studied the number
      and availability for ligand binding of the receptors for two targeting ligands.
      The results show that both paucity of total receptors and their poor availability
      are major bottlenecks in drug targeting. A tumour-penetrating peptide greatly
      increases the availability of receptors by promoting transport of the drug to the
      extravascular tumour tissue, but the number of available receptors still remains
      low, severely limiting the utility of the approach. Our results emphasize the
      importance of using drugs with high specific activity to avoid exceeding receptor
      capacity because any excess drug conjugate would lose the targeting advantage.
      The mathematical models we describe make it possible to focus on those aspects of
      the targeting mechanism that are most likely to have a substantial effect on the
      overall efficacy of the targeting. 

PMID- 24912982
TI  - Interactions with DCAF1 and DDB1 in the CRL4 E3 ubiquitin ligase are required for
      Vpr-mediated G2 arrest.
AB  - BACKGROUND: HIV-1 Vpr-mediated G2 cell cycle arrest is dependent on the
      interaction of Vpr with an E3 ubiquitin ligase that contains damage-specific DNA
      binding protein 1 (DDB1), Cullin 4A (Cul4A), DDB1 and Cul4-associated factor 1
      (DCAF1), and Rbx1. Vpr is thought to associate directly with DCAF1 in the E3
      ubiquitin ligase complex although the exact interaction pattern of the proteins
      in the complex is not completely defined. The Vpr of SIVagm induces G2 arrest of
      cognate African Green Monkey (AGM) cells but not human cells. The molecular
      mechanism by which SIVagm Vpr exhibits its species-specific function remained
      unknown. METHODS: Physical interaction of proteins in the E3 ubiquitin ligase
      complex was assessed by co-immunoprecipitation followed by western blotting. In
      addition, co-localization of the proteins in cells was investigated by confocal
      microscopy. The cell cycle was analyzed by propidium iodide staining and flow
      cytometry. DNA damage response elicited by Vpr was evaluated by detecting
      phosphorylation of H2AX, a marker for DNA damage response. RESULTS: We show that
      RNAi knock-down of DCAF1 prevented the co-immunoprecipitation of DDB1 with HIV-1
      Vpr while DDB1 knock-down did not influence the binding of Vpr to DCAF1. HIV-1
      Vpr mutants with a L64P or a R90K mutation maintained the ability to associate
      with DCAF1 but did not appear to be in a complex with DDB1. SIVagm Vpr associated
      with AGM DCAF1 and DDB1 while, in human cells, it binds to human DCAF1 but hardly
      binds to human DDB1, resulting in the reduced activation of H2AX. CONCLUSIONS:
      The identification of Vpr mutants which associate with DCAF1 but only poorly with
      DDB1 suggests that DCAF1 is necessary but the simple binding of Vpr to DCAF1 is
      not sufficient for the Vpr association with DDB1-containing E3 ligase complex.
      Vpr may interact both with DCAF1 and DDB1 in the E3 ligase complex.
      Alternatively, the interaction of Vpr and DCAF1 may induce a conformational
      change in DCAF1 or Vpr that promotes the interaction with DDB1. The ability of
      SIVagm Vpr to associate with DDB1, but not DCAF1, can explain the species
      specificity of SIVagm Vpr-mediated G2 arrest.

PMID- 24912983
TI  - Bipolar disorder, miscarriage, and termination.
AB  - OBJECTIVES: To compare rates of bipolar episodes following miscarriage and
      termination with those occurring in the postpartum period. METHODS: Information
      in relation to pregnancy and childbirth was gathered retrospectively for 1,283
      women with broadly defined bipolar disorder by interview and case-notes review.
      RESULTS: Rates of mania or affective psychosis were significantly higher after
      full-term delivery than after termination (p < 0.001) or miscarriage (p < 0.001).
      Rates of non-psychotic major depression were similar following full-term
      deliveries, miscarriages (p = 0.362), and terminations (p = 0.301). CONCLUSIONS:
      While women with bipolar disorder and their clinicians should be aware of the
      possible onset of depression in the weeks following miscarriage or termination,
      episodes of mania or affective psychosis are less common in comparison with the
      high rates observed in the postpartum period.

PMID- 24912985
TI  - Enhancement of dynein-mediated autophagosome trafficking and autophagy maturation
      by ROS in mouse coronary arterial myocytes.
AB  - Dynein-mediated autophagosome (AP) trafficking was recently demonstrated to
      contribute to the formation of autophagolysosomes (APLs) and autophagic flux
      process in coronary arterial myocytes (CAMs). However, it remains unknown how the
      function of dynein as a motor protein for AP trafficking is regulated under
      physiological and pathological conditions. The present study tested whether the
      dynein-mediated autophagy maturation is regulated by a redox signalling
      associated with lysosomal Ca(2+) release machinery. In primary cultures of CAMs,
      reactive oxygen species (ROS) including H2 O2 and O2 (-.) (generated by
      xanthine/xanthine oxidase) significantly increased dynein ATPase activity and AP
      movement, which were accompanied by increased lysosomal fusion with AP and APL
      formation. Inhibition of dynein activity by (erythro-9-(2-hydroxy-3
      nonyl)adenine) (EHNA) or disruption of the dynein complex by dynamitin (DCTN2)
      overexpression blocked ROS-induced dynein activation, AP movement and APL
      formation, and resulted in an accumulation of AP along with a failed breakdown of
      AP. Antagonism of nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated
      Ca(2+) signalling with NED-19 and PPADS abolished ROS-enhanced lysosomal Ca(2+)
      release and dynein activation in CAMs. In parallel, all these changes were also
      enhanced by overexpression of NADPH oxidase-1 (Nox1) gene in CAMs. Incubation
      with high glucose led to a marked O2 (-.) production compared with normoglycaemic
      CAMs, while Nox1 inhibitor ML117 abrogated this effect. Moreover, ML117 and NED
      19 and PPADS significantly suppressed dynein activity and APL formation caused by
      high glucose. Taken together, these data suggest that ROS function as important
      players to regulate dynein-dependent AP trafficking leading to efficient
      autophagic maturation in CAMs. 

PMID- 24912986
TI  - Pattern recognition pathways leading to a Th2 cytokine bias in allergic
      bronchopulmonary aspergillosis patients.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterised by an
      exaggerated Th2 response to Aspergillus fumigatus, but the immunological pathways
      responsible for this effect are unknown. OBJECTIVE: The aim of this study was to
      decipher the pattern recognition receptors (PRRs) and cytokines involved in the
      Aspergillus-specific Th2 response and to study Aspergillus-induced responses in
      healthy controls and ABPA patients. METHODS: Peripheral blood mononuclear cells
      (PBMCs) were stimulated with heat-killed Aspergillus conidia, various other
      pathogens, or PRR ligands. PRRs and cytokine pathways were blocked with PRR
      blocking reagents, anti-TNF (Etanercept or Adalimumab), IL-1Ra (Anakinra) or
      IFNgamma (IFN-gamma). ELISA and FACS were used to analyse cytokine responses.
      RESULTS: Aspergillus was the only pathogen that stimulated the Th2 cytokines IL-5
      and IL-13, while Gram-negative bacteria, Gram-positive bacteria, Candida
      albicans, chitin, beta-glucan or Toll-like receptor (TLR) ligands did not.
      Depletion of CD4(+) cells abolished IL-13 production. Blocking complement
      receptor 3 (CR3) significantly reduced IL-5 and IL-13, while blocking TLR2, TLR4
      or dectin-1 had no effect. ABPA patients displayed increased Aspergillus-induced
      IL-5 and IL-13 and decreased IFNgamma production compared with healthy controls.
      All biological agents tested showed the capability to inhibit Th2 responses, but
      also decreased Aspergillus-induced IFNgamma. CONCLUSIONS AND CLINICAL RELEVANCE:
      Aspergillus conidia are unique in triggering Th2 responses in human PBMCs,
      through a CR3-dependent pathway. ABPA patients display a significantly increased
      Aspergillus-induced Th2/Th1 ratio that can be modulated by biologicals. These
      data provide a rationale to explore IFNgamma therapy in ABPA as a corticosteroid
      sparing treatment option, by dampening Th2 responses and supplementing the
      IFNgamma deficiency at the same time.

PMID- 24912988
TI  - Highly conductive stretchable and biocompatible electrode-hydrogel hybrids for
      advanced tissue engineering.
AB  - Hydrogel-based, molecular permeable electronic devices are considered to be
      promising for electrical stimulation and recording of living tissues, either in
      vivo or in vitro. This study reports the fabrication of the first hydrogel-based
      devices that remain highly electrically conductive under substantial stretch and
      bending. Using a simple technique involving a combination of chemical
      polymerization and electropolymerization of poly (3,4-ethylenedioxythiophene)
      (PEDOT), a tight bonding of a conductive composite of PEDOT and polyurethane (PU)
      to an elastic double-network hydrogel is achieved to make fully organic PEDOT/PU
      hydrogel hybrids. Their response to repeated bending, mechanical stretching,
      hydration-dessication cycles, storage in aqueous condition for up to 6 months,
      and autoclaving is assessed, demonstrating excellent stability, without any
      mechanical or electrical damage. The hybrids exhibit a high electrical
      conductivity of up to 120 S cm(-1) at 100% elongation. The adhesion,
      proliferation, and differentiation of neural and muscle cells cultured on these
      hybrids are demonstrated, as well as the fabrication of 3D hybrids, advancing the
      field of tissue engineering with integrated electronics. 

PMID- 24912987
TI  - Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced
      experimental acute pancreatitis in rats.
AB  - AIM: Acute pancreatitis (AP) is defined as an inflammatory disease of the
      pancreas. The purpose of this study was to examine the effectiveness of Anakinra
      on cerulein-induced experimental pancreatitis rat model by using the results of
      biochemical and histopathological findings. MATERIALS AND METHODS: Cerulein was
      administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein
      was injected to the rats in group 2 for experimental pancreatitis group. In
      groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the
      induction of experimental pancreatitis by subcutaneous cerulein in rats,
      respectively. Lastly, in group 5, rats were injected with intraperitoneal saline
      and subcutan cerulean for placebo group. The following parameters were evaluated:
      histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF
      alpha levels, IL-1beta and the leukocyte count. RESULTS: When the results of
      serum amylase, lipase, TNF-alpha and IL-1beta levels, the leukocyte count,
      histopathologic scores and apoptotic indices of control group compared to the
      results of other groups, the differences exhibited statistical significance (all
      p < 0.05). On the other hand, when the results of fourth group compared with the
      results of third group, the data demonstrated statistical insignificance (p >
      0.05). However, no any significant differences were found between the results of
      fourth and fifth groups (p > 0.05). CONCLUSION: In the light of these results,
      cerulein is an appropriate agent for experimental AP rat model and Anakinra has a
      favorable therapeutic effect on acute experimental pancreatitis model. Moreover,
      Anakinra significantly decreases cerulein-related pancreatic tissue injury and
      pancreatic apoptosis.

PMID- 24912984
TI  - Macromolecular complexes at active zones: integrated nano-machineries for
      neurotransmitter release.
AB  - The release of neurotransmitters from synaptic vesicles exocytosing at
      presynaptic nerve terminals is a critical event in the initiation of synaptic
      transmission. This event occurs at specialized sites known as active zones. The
      task of faithfully executing various steps in the process is undertaken by
      careful orchestration of overlapping sets of molecular nano-machineries upon a
      core macromolecular scaffold situated at active zones. However, their composition
      remains incompletely elucidated. This review provides an overview of the role of
      the active zone in mediating neurotransmitter release and summarizes the recent
      progress using neuroproteomic approaches to decipher their composition. Key
      proteins of these nano-machineries are highlighted. 

PMID- 24912990
TI  - Enzymatic hydrolysis-based absolute quantification of triacylglycerols in plant
      oil by use of a single marker.
AB  - Absolute quantification of triacylglycerols (TAGs) in plant oils is a challenge
      for analysts, because most of the necessary chemical standards are unavailable.
      In this study, a new method for absolute quantification analysis of multi
      components by use of a single marker (AQAMS), using two crucial technologies,
      evaluation of the collection recovery without chemical standards and enzymatic
      hydrolysis, was used for determining the absolute content of TAGs in brucea
      javanica oil (BJO), using glycerol as the marker. The TAGs in BJO were initially
      characterized using ultrafast liquid chromatography tandem atmospheric-pressure
      chemical-ionization mass spectrometry. Then the TAGs in BJO were individually
      collected, by target-fraction collection via high-performance liquid
      chromatography coupled with an evaporative-light-scattering detector (HPLC-ELSD),
      and their recoveries were calculated by use of a novel non-standard evaluated
      recovery strategy (NSER). The results revealed that the collection procedure was
      feasible and reliable. Finally, modified commercial TAG assay kits using glycerol
      as the marker were used to determine the absolute abundance of individual TAGs in
      the plant oils. Comparing the result with that obtained by HPLC-ELSD analysis
      using triolein standard, the content of triolein determined by AQAMS was closely
      matched. The proposed strategy is a practical measure for solving the problem of
      the lack of chemical standards, and provides a new method for absolute
      quantification in natural products of multi-components with the same backbone. 

PMID- 24912989
TI  - Icariin combined with breviscapine improves the erectile function of
      spontaneously hypertensive rats.
AB  - INTRODUCTION: The impaired erectile response in spontaneously hypertensive rats
      (SHR) is caused by increased signaling of RhoA/Rho-kinase and decreased signaling
      of nitric oxide (NO). Icariin improves erectile function via upregulating
      multitargets in NO/cyclic guanosine monophosphate (NO/cGMP) pathway, which
      breviscapine accomplishes by downregulating RhoA/Rho-kinase pathway. AIM: To
      investigate the effect and mechanism of icariin combined with breviscapine on the
      erectile function of SHR. METHODS: Five 12-week-old male Wistar-Kyoto (WKY) rats
      and 20 age-matched male SHR were evenly randomized into WKY rats control group,
      SHR control group, icariin-treated group, breviscapine-treated group, and
      combined treatment group treated by vehicle, icariin, breviscapine, and icariin
      plus breviscapine, respectively, by gavage for four successive weeks. Maximum
      intracavernosal pressure/mean arterial pressure (ICPmax/MAP) and the expression
      of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase
      (nNOS), phosphodiesterase type 5 inhibitors (PDE5), and Rho-associated, coiled
      coil containing protein kinase 1 and 2 (ROCK1 and ROCK2) in the cavernous tissues
      were determined. RESULTS: The ICPmax/MAP in the combined treatment group was
      significantly increased compared with SHR control group, icariin-treated group,
      and breviscapine-treated group. The expression of eNOS and nNOS was significantly
      higher in the combined treatment group than in SHR control group, icariin-treated
      group, and breviscapine-treated group (P < 0.05). The expression of PDE5 was
      significantly lower in the icariin-treated group than in SHR control group (P <
      0.05). The expression of ROCK1 was significantly lower in the combined treatment
      group than in other groups (P < 0.05). The expression of ROCK2 was significantly
      higher in SHR control group than in WKY rats control group, icariin-treated
      group, and combined treatment group (P < 0.05). Among these groups, the
      expression of eNOS and nNOS was the strongest, and ROCK1 was the lowest in WKY
      rats control group. CONCLUSION: Icariin combined with breviscapine has
      synergistic effects on erectile function of SHR through different signal
      pathways.

PMID- 24912991
TI  - Determination of sulfadiazine in phosphate- and DOC-rich agricultural drainage
      water using solid-phase extraction followed by liquid chromatography-tandem mass
      spectrometry.
AB  - Trace levels of the veterinary antibiotic compound sulfadiazine (SDZ) can be
      determined in agricultural drainage water samples with this new method. Optimized
      sample pretreatment and solid-phase extraction was combined with liquid
      chromatography coupled to tandem mass spectrometry (SPE LC-MS/MS) using positive
      electrospray ionization. The linear dynamic range for the LC-MS/MS was assessed
      from 5 MUg/L to 25 mg/L with a 15-point calibration curve displaying a
      coefficient of correlation r(2) = 0.9915. Agricultural drainage water spiked at a
      concentration of 25 ng/L gave recoveries between 63 and 98 % (relative standard
      deviation 15 %), while at 10 ng/L, it showed a lower recovery of 32 % (relative
      standard deviation 47 %). The final SPE LC-MS/MS method had a limit of detection
      (LOD)(Method) and a limit of quantification (LOQ)(Method) of 7.5 and 23 ng/L
      agricultural drainage water, respectively. Determination of SDZ, spiked at a
      realistic concentration of 50 MUg/L, in artificial drainage water (ADW)
      containing common and high levels of phosphate (0.05, 0.5, and 5 mg/L) gave
      recoveries between 70 and 92 % (relative standard deviation 7.4-12.9 %). Analysis
      of the same realistic concentration of SDZ in ADW, spiked with common and high
      levels of dissolved organic carbon (2, 6, and 15 mg/L) confirmed the possible
      adaptation of a tandem solid-phase extraction (strong anion exchange (SAX)
      hydrophilic-lipophilic balance (HLB)) followed by liquid chromatography-tandem
      mass spectrometry methodology. Recoveries obtained ranged from 104 to 109 %
      (relative standard deviation 2.8-5.2 %). The new methods enable determination of
      the veterinary antibiotic compound SDZ in agricultural drainage water from field
      experiments and monitoring schemes for phosphate- and dissolved organic carbon
      (DOC)-rich water samples in intensive farming areas.

PMID- 24912993
TI  - Thermal string excitations in artificial spin-ice square dipolar array.
AB  - We report on a theoretical investigation of artificial spin-ice dipolar arrays
      using a nanoisland shape adopted from recent experiments (Farhan et al 2013
      Nature Phys. 9 375). The number of thermal magnetic string excitations in the
      square lattice is drastically increased by a vertical displacement of rows and
      columns. We find large increments especially for low temperatures and for string
      excitations with quasi-monopoles of charges +/- 4. By kinetic Monte Carlo
      simulations we address the thermal stability of such excitations, thereby
      providing time scales for their experimental observation.

PMID- 24912992
TI  - Hepatoprotective effects of secoiridoid-rich extracts from Gentiana cruciata L.
      against carbon tetrachloride induced liver damage in rats.
AB  - The objective of this work was to investigate the effects of the methanol
      extracts of Gentiana cruciata L. aerial parts (GCA) and roots (GCR) against
      carbon tetrachloride-induced liver injury in rats. Pretreatment with GCA and GCR,
      containing sweroside, swertiamarin and gentiopicrin in high concentrations, dose
      dependently and significantly decreased the levels of serum transaminases,
      alkaline phosphatase and total bilirubin, whereas an increase in the level of
      total protein was found compared with the CCl4-treated group. Moreover, oral
      administration of extracts significantly enhanced antioxidant enzyme activities
      (superoxide dismutase and catalase), increased the content of glutathione and
      decreased the content of TBARS. Microscopic evaluations of the liver revealed
      CCl4-induced lesions and related toxic manifestations that were minimal in the
      liver of rats pretreated with extracts at the dose of 400 mg per kg b.w. The
      results suggest that the use of G. cruciata extracts has a merit as a potent
      candidate in protecting the liver against chemical induced toxicity. 

PMID- 24912994
TI  - Characterization of "Candidatus Liberibacter asiaticus" populations by double
      locus analyses.
AB  - "Candidatus Liberibacter asiaticus" (CaLas) is associated with citrus
      Huanglongbing (HLB, yellow shoot disease), which is highly destructive to world
      citrus production. Understanding the relationships of CaLas isolates from
      different geographical regions is important for HLB research and development of
      disease management strategies. In this study, 301 CaLas isolates [85 Brazil, 132
      China, and 84 U.S. (83 Florida and 1 California)] were collected, and genomic
      variations among them were evaluated based on the analyses of two genomic loci:
      trn1, characteristic of variable tandem repeat numbers (TRNs), and snp1,
      characteristic of single nucleotide polymorphisms (SNPs). Locus trn1 revealed the
      homogeneity of all Brazilian isolates, and locus snp1 revealed the homogeneity of
      most Florida isolates. When the two loci were analyzed simultaneously, i.e.,
      double-locus (DL) analyses, CaLas isolates were clustered mostly according to
      geographical origins. DL genotype 1 included 97 % of the Chinese isolates, DL
      genotype 2 included all Brazilian isolates, and DL genotype 3 included 93 % of
      the U.S. isolates. DL analyses successfully revealed inter-continental
      overlapping or movement pattern of CaLas isolates. The isolate recently found in
      California belonged to Asiatic DL genotype 1. 

PMID- 24912996
TI  - [Correlation between the magnitude of skin prick test reactivity and pollen
      specific serum IgE levels in patients with respiratory allergy].
AB  - BACKGROUND: For the etiological diagnosis of allergic respiratory diseases skin
      tests or specific serum IgE determination are used. OBJECTIVE: To determine the
      correlation between the extent of reactivity to cutaneous prick tests and the
      levels of pollen specific serum IgE in patients with respiratory allergy.
      PATIENTS AND METHODS: A prolective, descriptive and transversal study was done
      with patients of both genders, aged 2 to 60 years, who attended for the first
      time at the service of Allergy and Clinical Immunology of University Hospital of
      Puebla, Mexico, with presumptive diagnosis of respiratory allergy. All patients
      underwent clinical history, skin prick tests with standardized allergenic
      extracts and quantification of pollen specific serum IgE by chemiluminescence
      method. We estimated the correlation index r using the statistical method Pearson
      product-moment correlation coefficient; a value r equal to or higher than 0.70
      was considered a significant relationship or a high correlation. RESULTS: Nine
      one patients were included, of whom 58.2% were female. The diagnoses were:
      allergic rhinitis (79.1%), asthma and allergic rhinitis (16.5%) and only asthma
      (4.4%). Only significant correlation was found in patients with allergic rhinitis
      for Rumex crispus (r = 0.702) and in patients with asthma and rhinitis for
      Ambrosia trifida (r = 1). CONCLUSION: Only for Rumex crispus and Ambrosia
      trifida, the skin prick tests or the determination of specific serum IgE levels
      are comparable diagnostic methods of allergic respiratory diseases.

PMID- 24912997
TI  - [Sensitization to Casuarina equisetifolia and Pinus spp pollen in patients with
      allergic rhinitis and asthma in Mexico City].
AB  - BACKGROUND: Pollinosis studies at Mexico City have found a considerable amount of
      Casuarina equisetifolia and Pinus spp pollen, its sensitization frequency is
      unknown. In Mexico, some allergens are not considered related to asthma or
      allergic rhinitis, even though reports in other countries have been demonstrated
      their relevance as aeroallergens. OBJECTIVE: To estimate the frequency of
      sensitization to Casuarina equisetifolia and Pinus spp pollen. PATIENTS AND
      METHOD: A transversal, descriptive trial was done at Hospital General de Mexico.
      Previous informed consent 142 patients with allergic rhinitis and asthma, 3 to 55
      years old, were included to the study. A complete clinical evaluation, laboratory
      tests and skin prick tests were performed. RESULTS: We included 142 patients, 44
      children (64% males) and 98 adults (73% females). We found that 8 (18.18%)
      children and 35 (35.7%) adults had a positive skin prick test to Casuarina
      equisetifolia. None of the patients included in the study had a positive skin
      prick test to Pinus spp. CONCLUSIONS: Sensitization to Casuarina equisetifolia is
      as important as other pollens found in Mexico City. These results suggest that it
      should be included when skin prick tests are performed. Pinus spp pollen is
      considered an aeroallergen in European countries but we did not corroborate
      sensitization in our population.

PMID- 24912998
TI  - Prevalence of DRESS syndrome.
AB  - DRESS syndrome (Drug rash with Eosinophilia and Systemic Symptoms) is an
      idiosyncratic reaction (type B), characterized by peripheral eosinophilia and
      systemic symptoms, such as fever, rash, lymphadenopathy, hepatitis, atypical
      lymphocytes and elevation of liver enzymes at least twice its normal level or
      increase of alanine amino transferase (ALT) >100 U/L. Its incidence is of 1/1,000
      to 10,000 exposures and its mortality is of 10%-20%. Treatment is based on
      steroids and on the suspension of the suspect drug. This paper reports the cases
      of six patients with DRESS syndrome attended at Centro Medico Nacional Siglo XXI,
      Mexico City, from September 2012 to September 2013, which accounted for 12.5% of
      patients attended with adverse reactions to drugs. 

PMID- 24912999
TI  - [Anaphylaxis secondary to prick-to-prick tests to foods and its risk factors].
AB  - The diagnosis of food allergy requires a proper anamnesis and diagnostic testing
      with skin prick tests with fresh foods and/or standardized allergen, or specific
      IgE tests. The risk of systemic reactions is of 15-23 per 100,000 skin tests
      performed by prick method, specifically anaphylaxis at 0.02%. This paper reports
      the case of four patients, who while performing prick to prick test with fresh
      food presented anaphylactic reaction. Implicated foods were fruits of the
      Rosaceae, Anacardiaceae and Caricaceae families. The severity of anaphylaxis was:
      two patients with grade 4, one patient grade 2 and one grade 3, all with
      appropriate response to drug treatment. The risk factors identified were: female
      sex, personal history of atopy, previous systemic reaction to Hymenoptera venom,
      prior anaphylaxis to prick tests to aeroallergens. We found that a history of
      positive skin test for Betulla v, can be a risk factor for anaphylaxis in
      patients with oral syndrome. During testing prick to prick with food anaphylaxis
      can occur, so it should be made with aerial red team on hand. The history of
      positivity Betulla v is an additional risk factor in these patients. 

PMID- 24913000
TI  - [Utility of challenge test in immediate hypersensitivity to hydrocortisone sodium
      succinate].
AB  - Corticosteroid hypersensitivity is a complex phenomenon in which many factors
      interact, such as idiosyncrasy, intolerance or allergic reactions. The prevalence
      of immediate hypersensitivity reactions to corticosteroids is 0.2%-0.5%.
      Corticosteroids have major therapeutic implications; thus, when hypersensitivity
      is suspected, in-vitro and/or in-vivo testing can be performed to confirm
      diagnosis, being the drug challenge the gold standard. After definitive
      diagnosis, cross-reactivity among the different corticosteroid groups should be
      considered, to choose wisely if corticosteroid therapy is still required. In
      Coopman classification, steroids belonging to groups A, B and D2 have high cross
      reactivity, however, more studies are needed to determine the degree of cross
      reaction among these drugs. This paper presents the case of a woman, in who
      hypersensitivity to hydrocortisone succinate was confirmed by drug challenge
      test. 

PMID- 24913001
TI  - [Unilateral pulmonary artery agenesis with ipsilateral pulmonary hypoplasia as
      incidental finding in an asthmatic patient].
AB  - Unilateral absence of a pulmonary artery is an uncommon congenital heart disease.
      It can be related to respiratory symptoms such as asthma, an unusual finding in
      some of these patients. This paper reports the case of a 4-year-old male with
      recurrent respiratory infections and asthma symptoms, in who further studies
      found agenesia of right pulmonary artery with pulmonary hypoplasia of the same
      side.

PMID- 24913002
TI  - Split decision.

PMID- 24913003
TI  - The care transitions innovation (C-TraIn) for socioeconomically disadvantaged
      adults: results of a cluster randomized controlled trial.
AB  - BACKGROUND: Despite growing emphasis on transitional care to reduce costs and
      improve quality, few studies have examined transitional care improvements in
      socioeconomically disadvantaged adults. It is important to consider these
      patients separately as many are high-utilizers, have different needs, and may
      have different responses to interventions. OBJECTIVE: To evaluate the impact of a
      multicomponent transitional care improvement program on 30-day readmissions,
      emergency department (ED) use, transitional care quality, and mortality. DESIGN:
      Clustered randomized controlled trial conducted at a single urban academic
      medical center in Portland, Oregon. PARTICIPANTS: Three hundred eighty-two
      hospitalized low-income adults admitted to general medicine or cardiology who
      were uninsured or had public insurance. INTERVENTION: Multicomponent intervention
      including (1) transitional nurse coaching and education, including home visits
      for highest risk patients; (2) pharmacy care, including provision of 30 days of
      medications after discharge for those without prescription drug coverage; (3)
      post-hospital primary care linkages; (4) systems integration and continuous
      quality improvement. MEASUREMENTS: Primary outcomes included 30-day inpatient
      readmission and ED use. Readmission data were obtained using state-wide
      administrative data for all participants (insured and uninsured). Secondary
      outcomes included quality (3-item Care Transitions Measure) and mortality.
      Research staff administering questionnaires and assessing outcomes were blinded.
      RESULTS: There was no significant difference in 30-day readmission between C
      TraIn (30/209, 14.4 %) and control patients (27/173, 16.1 %), p = 0.644, or in ED
      visits between C-TraIn (51/209, 24.4 %) and control (33/173, 19.6 %), p = 0.271.
      C-TraIn was associated with improved transitional care quality; 47.3 % (71/150)
      of C-TraIn patients reported a high quality transition compared to 30.3 %
      (36/119) control patients, odds ratio 2.17 (95 % CI 1.30-3.64). Zero C-TraIn
      patients died in the 30-day post-discharge period compared with five in the
      control group (unadjusted p = 0.02). CONCLUSIONS: C-TraIn did not reduce 30-day
      inpatient readmissions or ED use; however, it improved transitional care quality.

PMID- 24913004
TI  - Resident duty hours: a survey of internal medicine program directors.
AB  - INTRODUCTION: In 2011, the Accreditation Council for Graduate Medical Education
      (ACGME) implemented new Common Program Requirements to regulate duty hours of
      resident physicians, with three goals: improved patient safety, quality of
      resident education and quality of life for trainees. We sought to assess Internal
      Medicine program director (IMPD) perceptions of the 2011 Common Program
      Requirements in July 2012, one year following implementation of the new
      standards. METHODS: A cross-sectional study of all IMPDs at ACGME-accredited
      programs in the United States (N = 381) was performed using a 32-question, self
      administered survey. Contact information was identified for 323 IMPDs. Three
      individualized emails were sent to each director over a 6-week period, requesting
      participation in the survey. Outcomes measured included approval of duty hours
      regulations, as well as perceptions of changes in graduate medical education and
      patient care resulting from the revised ACGME standards. RESULTS: A total of 237
      surveys were returned (73% response rate). More than half of the IMPDs (52%)
      reported "overall" approval of the 2011 duty hour regulations, with greater than
      70% approval of all individual regulations except senior resident daily duty
      periods (49% approval) and 16-hour intern shifts (17% approval). Although a
      majority feel resident quality of life has improved (55%), most IMPDs believe
      that resident education (60%) is worse. A minority report that quality (8%) or
      safety (11%) of patient care has improved. CONCLUSION: One year after
      implementation of new ACGME duty hour requirements, IMPDs report overall approval
      of the standards, but strong disapproval of 16-hour shift limits for interns. Few
      program directors perceive that the duty hour restrictions have resulted in
      better care for patients or education of residents. Although resident quality of
      life seems improved, most IMPDs report that their own workload has increased.
      Based on these results, the intended benefits of duty hour regulations may not
      yet have been realized.

PMID- 24913005
TI  - Notch1 is an important mediator for enhancing of B-cell activation and antibody
      secretion by Notch ligand.
AB  - The roles of Notch1 and Notch2 in T-cell function have been well studied, but the
      functional roles of Notch in B cells have not been extensively investigated,
      except for Notch2 involvement in peripheral marginal zone B-cell differentiation.
      This study examined the roles of Notch1 in murine primary B cells. During B-cell
      activation by B-cell receptor ligation, Notch1 was up-regulated while Notch2 was
      not. In addition, Notch1 up-regulation itself did not contribute to the further
      activation of B cells, but the Notch ligand was important for Notch1-mediated
      further B-cell activation. Moreover, Notch1 deficiency significantly decreased B
      cell activation and antibody secretion under the presence of Notch ligand. These
      data suggest that Notch1 is an important mediator for enhancing B-cell activation
      and antibody secretion by Notch ligand. 

PMID- 24913007
TI  - Intake fraction variability between air pollution emission sources inside an
      urban area.
AB  - The cost-effective mitigation of adverse health effects caused by air pollution
      requires information on the contribution of different emission sources to
      exposure. In urban areas the exposure potential of different sources may vary
      significantly depending on emission height, population density, and other
      factors. In this study, we quantified this intraurban variability by predicting
      intake fraction (iF) for 3,066 emission sources in Warsaw, Poland. iF describes
      the fraction of the pollutant that is inhaled by people in the study area. We
      considered the following seven pollutants: particulate matter (PM), nitrogen
      oxides (NOx), sulfur dioxide (SO2), benzo[a] pyrene (BaP), nickel (Ni), cadmium
      (Cd), and lead (Pb). Emissions for these pollutants were grouped into four
      emission source categories (Mobile, Area, High Point, and Other Point sources).
      The dispersion of the pollutants was predicted with the CALPUFF dispersion model
      using the year 2005 emission rate data and meteorological records. The resulting
      annual average concentrations were combined with population data to predict the
      contribution of each individual source to population exposure. The iFs for
      different pollutant-source category combinations varied between 51 per million
      (PM from Mobile sources) and 0.013 per million (sulfate PM from High Point
      sources). The intraurban iF variability for Mobile sources primary PM emission
      was from 4 per million to 100 per million with the emission-weighted iF of 44 per
      million. These results propose that exposure due to intraurban air pollution
      emissions could be decreased more effectively by specifically targeting sources
      with high exposure potency rather than all sources.

PMID- 24913006
TI  - The silencing of the SWI/SNF subunit and anticancer gene BRM in Rhabdoid tumors.
AB  - Rhabdoid sarcomas are highly malignant tumors that usually occur in young
      children. A key to the genesis of this tumor is the mutational loss of the BAF47
      gene as well as the widespread epigenetic suppression of other key anticancer
      genes. The BRM gene is one such epigenetically silenced gene in Rhabdoid tumors.
      This gene codes for an ATPase catalytic subunit that shifts histones and opens
      the chromatin. We show that BRM is an epigenetically silenced gene in 10/11
      Rhabdoid cell lines and in 70% of Rhabdoid tumors. Moreover, BRM can be induced
      by BAF47 re-expression and by Flavopiridol. By selective shRNAi knockdown of BRM,
      we show that BRM re-expression is necessary for growth inhibition by BAF47 re
      expression or Flavopiridol application. Similar to lung cancer cell lines, we
      found that HDAC3, HDAC9, MEF2D and GATA3 controlled BRM silencing and that HDAC9
      was overexpressed in Rhabdoid cancer cell lines. In primary BRM-deficient
      Rhabdoid tumors, HDAC9 was also found to be highly overexpressed. Two insertional
      BRM promoter polymorphisms contribute to BRM silencing, but only the -1321
      polymorphism correlated with BRM silencing in Rhabdoid cell lines. To determine
      how these polymorphisms were tied to BRM silencing, we conducted ChIP assays and
      found that both HDAC9 and MEF2D bound to the BRM promoter at or near these
      polymorphic sites. Using BRM promoter swap experiments, we indirectly showed that
      both HDAC9 and MEF2D bound to these polymorphic sites. Together, these data show
      that the mechanism of BRM silencing contributes to the pathogenesis of Rhabdoid
      tumors and appears to be conserved among tumor types. 

PMID- 24913008
TI  - Sleep-readiness signals in insomniacs and good sleepers.
AB  - Sleep is preceded by physiological and behavioural events that inform the subject
      that it is time to sleep. Our hypothesis is that insomniacs do not adequately
      recognize such signals, thus missing the best time to go to bed. Eighty-seven
      chronic insomniac participants and 76 age-matched good sleeper controls were
      recruited. Semi-structured interviews focused on three aspects of nocturnal
      sleep: features, habitual activities and signals that they usually rely on in
      order to decide their readiness to sleep. The results showed that insomniacs
      relied more than good sleepers on external signals (time) than on bodily ones to
      decide to go to sleep.

PMID- 24913009
TI  - Participant attributions for global change ratings in unexplained chronic fatigue
      and chronic fatigue syndrome.
AB  - The purpose of this mixed methods study was to identify participants'
      attributions for their global impression of change ratings in a behavioral
      intervention for unexplained chronic fatigue and chronic fatigue syndrome. At 3
      month follow-up, participants (N = 67) were asked "Why do you think you are
      (improved, unchanged, worse)?" Improved patients pointed to specific behavioral
      changes, unchanged patients referred to a lack of change in lifestyle, and
      worsened patients invoked stress and/or specific life events. Identifying patient
      perceptions of behaviors associated with patient global impression of change
      rated improvement and non-improvement may assist in developing more effective
      management strategies in clinical care.

PMID- 24913010
TI  - (Re-)defining the self - Enhanced posttraumatic growth and event centrality in
      stroke survivors: A mixed-method approach and control comparison study.
AB  - Growing evidences highlight the co-existence of negative and positive (e.g.
      posttraumatic growth) identity changes following stroke. Identity changes were
      assessed by comparing 42 survivors 21 months after stroke and healthy controls. A
      total of 26 stroke survivors participated in a semi-structured interview. Stroke
      survivors showed significantly higher posttraumatic growth (F(1, 75) = 9.79, p =
      .003) and integrated the critical life event to a higher extent into their
      identity (event centrality) (F(1, 74) = 37.54, p < .001). Qualitative analysis
      revealed increased appreciation of life and more intense/selective relationships
      as the most common positive changes. Considering positive changes might provide
      additional perspectives for rehabilitation.

PMID- 24913011
TI  - Chemical constituents from the fungus Chaetomium cupreum RY202.
AB  - Two new angular types of azaphilones, isochromophilonol (1) and ochrephilonol
      (2), together with ten known compounds (3-12), were isolated from Chaetomium
      cupreum RY202. Their structures were established on the basis of spectroscopic
      data and the absolute configurations of 1 and 3 were determined by the modified
      Mosher's method. Compounds 1, 2 and 4 showed moderated cytotoxicity against KB
      and NCI-H187 cell lines (IC50 9.63-32.42 ug/mL). 

PMID- 24913013
TI  - The use of ozone to extend the shelf-life and maintain quality of fresh produce.
AB  - Fresh produce has been recognised as a healthy food, thus there is increasing
      consumer demand for fresh fruit and vegetables. The shelf-life of fresh produce,
      however, is relatively short and is limited by microbial contamination or visual,
      textural and nutritional quality loss. There are many methods to reduce/eliminate
      microorganisms present in food and ozone treatment is one of them. The use of
      ozone by the fresh produce industry is a good alternative to chemical treatments,
      e.g. the use of chlorine. The effectiveness of ozone as an antimicrobial agent
      has previously been reviewed and has been updated here, with the latest findings.
      The main focus of this review is on the effects of ozone on the fresh produce
      quality, defined by maintenance of texture, visual quality, taste and aroma, and
      nutritional content. Furthermore, ozone has been found to be efficient in
      reducing pesticide residues from the produce. The treatments that have the
      ability to reduce microbial contamination of the product without having an
      adverse effect on its visual, textural and nutritional quality can be recommended
      and subsequently incorporated into the supply chain. A good understanding of all
      the benefits and limitations related to the use of ozone is needed, and relevant
      information has been reviewed in this paper.

PMID- 24913012
TI  - Addressing phenoconversion: the Achilles' heel of personalized medicine.
AB  - Phenoconversion is a phenomenon that converts genotypic extensive metabolizers
      (EMs) into phenotypic poor metabolizers (PMs) of drugs, thereby modifying their
      clinical response to that of genotypic PMs. Phenoconversion, usually resulting
      from nongenetic extrinsic factors, has a significant impact on the analysis and
      interpretation of genotype-focused clinical outcome association studies and
      personalizing therapy in routine clinical practice. The high phenotypic
      variability or genotype-phenotype mismatch, frequently observed due to
      phenoconversion within the genotypic EM population, means that the real number of
      phenotypic PM subjects may be greater than predicted from their genotype alone,
      because many genotypic EMs would be phenotypically PMs. If the phenoconverted
      population with genotype-phenotype mismatch, most extensively studied for CYP2D6,
      is as large as the evidence suggests, there is a real risk that genotype-focused
      association studies, typically correlating only the genotype with clinical
      outcomes, may miss clinically strong pharmacogenetic associations, thus
      compromising any potential for advancing the prospects of personalized medicine.
      This review focuses primarily on co-medication-induced phenoconversion and
      discusses potential approaches to rectify some of the current shortcomings. It
      advocates routine phenotyping of subjects in genotype-focused association studies
      and proposes a new nomenclature to categorize study populations. Even with strong
      and reliable data associating patients' genotypes with clinical outcome(s), there
      are problems clinically in applying this knowledge into routine pharmacotherapy
      because of potential genotype-phenotype mismatch. Drug-induced phenoconversion
      during routine clinical practice remains a major public health issue. Therefore,
      the principal challenges facing personalized medicine, which need to be
      addressed, include identification of the following factors: (i) drugs that are
      susceptible to phenoconversion; (ii) co-medications that can cause
      phenoconversion; and (iii) dosage amendments that need to be applied during and
      following phenoconversion. 

PMID- 24913015
TI  - Automatic setae segmentation from Chaetoceros microscopic images.
AB  - A novel image processing model Grayscale Surface Direction Angle Model (GSDAM) is
      presented and the algorithm based on GSDAM is developed to segment setae from
      Chaetoceros microscopic images. The proposed model combines the setae
      characteristics of the microscopic images with the spatial analysis of image
      grayscale surface to detect and segment the direction thin and long setae from
      the low contrast background as well as noise which may make the commonly used
      segmentation methods invalid. The experimental results show that our algorithm
      based on GSDAM outperforms the boundary-based and region-based segmentation
      methods Canny edge detector, iterative threshold selection, Otsu's thresholding,
      minimum error thresholding, K-means clustering, and marker-controlled watershed
      on the setae segmentation more accurately and completely.

PMID- 24913014
TI  - Molecular identification for epigallocatechin-3-gallate-mediated antioxidant
      intervention on the H2O2-induced oxidative stress in H9c2 rat cardiomyoblasts.
AB  - BACKGROUND: Epigallocatechin-3-gallate (EGCG) has been documented for its
      beneficial effects protecting oxidative stress to cardiac cells. Previously, we
      have shown the EGCG-mediated cardiac protection by attenuating reactive oxygen
      species and cytosolic Ca2+ in cardiac cells during oxidative stress and
      myocardial ischemia. Here, we aimed to seek a deeper elucidation of the molecular
      anti-oxidative capabilities of EGCG in an H2O2-induced oxidative stress model of
      myocardial ischemia injury using H9c2 rat cardiomyoblasts. RESULTS: Proteomics
      analysis was used to determine the differential expression of proteins in H9c2
      cells cultured in the conditions of control, 400 MUM H2O2 exposure for 30 min
      with and/or without 10 to 20 MUM EGCG pre-treatment. In this model, eight
      proteins associated with energy metabolism, mitochondrial electron transfer,
      redox regulation, signal transduction, and RNA binding were identified to take
      part in EGCG-ameliorating H2O2-induced injury in H9c2 cells. H2O2 exposure
      increased oxidative stress evidenced by increases in reactive oxygen species and
      cytosolic Ca2+ overload, increases in glycolytic protein, alpha-enolase,
      decreases in antioxidant protein, peroxiredoxin-4, as well as decreases in
      mitochondrial proteins, including aldehyde dehydrogenase-2, ornithine
      aminotransferase, and succinate dehydrogenase ubiquinone flavoprotein subunit.
      All of these effects were reversed by EGCG pre-treatment. In addition, EGCG
      attenuated the H2O2-induced increases of Type II inositol 3, 4-bisphosphate 4
      phosphatase and relieved its subsequent inhibition of the downstream signalling
      for Akt and glycogen synthase kinase-3beta (GSK-3beta)/cyclin D1 in H9c2 cells.
      Pre-treatment with EGCG or GSK-3beta inhibitor (SB 216763) significantly improved
      the H2O2-induced suppression on cell viability, phosphorylation of pAkt (S473)
      and pGSK-3beta (S9), and level of cyclin D1 in cells. CONCLUSIONS: Collectively,
      these findings suggest that EGCG blunts the H2O2-induced oxidative effect on the
      Akt activity through the modulation of PIP3 synthesis leading to the subsequent
      inactivation of GSK-3beta mediated cardiac cell injury.

PMID- 24913017
TI  - Adequate and anticipatory research on the potential hazards of emerging
      technologies: a case of myopia and inertia?
AB  - History confirms that while technological innovations can bring many benefits,
      they can also cause much human suffering, environmental degradation and economic
      costs. But are we repeating history with new and emerging chemical and
      technological products? In preparation for volume 2 of 'Late Lessons from Early
      Warnings' (European Environment Agency, 2013), two analyses were carried out to
      help answer this question. A bibliometric analysis of research articles in 78
      environmental, health and safety (EHS) journals revealed that most focused on
      well-known rather than on newly emerging chemicals. We suggest that this
      'scientific inertia' is due to the scientific requirement for high levels of
      proof via well replicated studies; the need to publish quickly; the use of
      existing intellectual and technological resources; and the conservative approach
      of many reviewers and research funders. The second analysis found that since 1996
      the funding of EHS research represented just 0.6% of the overall funding of
      research and technological development (RTD). Compared with RTD funding, EHS
      research funding for information and communication technologies, nanotechnology
      and biotechnology was 0.09%, 2.3% and 4% of total research, respectively. The low
      EHS research ratio seems to be an unintended consequence of disparate funding
      decisions; technological optimism; a priori assertions of safety; collective
      hubris; and myopia. In light of the history of past technological risks, where
      EHS research was too little and too late, we suggest that it would be prudent to
      devote some 5-15% of RTD on EHS research to anticipate and minimise potential
      hazards while maximising the commercial longevity of emerging technologies. 

PMID- 24913016
TI  - A goal-based mechanism for delayed motor intention: considerations from motor
      skills, tool use and action memory.
AB  - Thinking about our behaviors for a future recall like playing a piano sonata
      during the next weekend (i.e., delayed motor intention) should engage at some
      level sensorimotor-based representations. Theoretically, such representations can
      be stored through both an action- and a goal-based mechanism. An action-based
      mechanism is related to the specific motor sequence of fingers like the key
      presses on the piano, and a goal-based mechanism is related to the musical tones
      generated by the key presses. From these considerations, the present article
      tries to explore whether the cognitive nature of delayed motor intention is more
      based on an action or goal mechanism. We reviewed empirical evidence and
      theoretical accounts of different domains such as motor skills, tool use, and
      action memory supporting the idea that such delayed motor intentions are rather
      represented through a goal-based mechanism. The specific role of this goal-based
      mechanism is to envision the future in an implementation-neutral mode to flexibly
      and efficiently retrieve an adapted action to environmental constraints. This
      goal-based account offers an interesting alternative to reshape the classical
      models about the representations of delayed motor intention. We also discuss how
      this account can be applied to practical activities in daily life situations. 

PMID- 24913018
TI  - Traffic-related air pollution and obesity formation in children: a longitudinal,
      multilevel analysis.
AB  - BACKGROUND: Biologically plausible mechanisms link traffic-related air pollution
      to metabolic disorders and potentially to obesity. Here we sought to determine
      whether traffic density and traffic-related air pollution were positively
      associated with growth in body mass index (BMI = kg/m2) in children aged 5-11
      years. METHODS: Participants were drawn from a prospective cohort of children who
      lived in 13 communities across Southern California (N = 4550). Children were
      enrolled while attending kindergarten and first grade and followed for 4 years,
      with height and weight measured annually. Dispersion models were used to estimate
      exposure to traffic-related air pollution. Multilevel models were used to
      estimate and test traffic density and traffic pollution related to BMI growth.
      Data were collected between 2002-2010 and analyzed in 2011-12. RESULTS: Traffic
      pollution was positively associated with growth in BMI and was robust to
      adjustment for many confounders. The effect size in the adjusted model indicated
      about a 13.6% increase in annual BMI growth when comparing the lowest to the
      highest tenth percentile of air pollution exposure, which resulted in an increase
      of nearly 0.4 BMI units on attained BMI at age 10. Traffic density also had a
      positive association with BMI growth, but this effect was less robust in
      multivariate models. CONCLUSIONS: Traffic pollution was positively associated
      with growth in BMI in children aged 5-11 years. Traffic pollution may be
      controlled via emission restrictions; changes in land use that promote jobs
      housing balance and use of public transit and hence reduce vehicle miles
      traveled; promotion of zero emissions vehicles; transit and car-sharing programs;
      or by limiting high pollution traffic, such as diesel trucks, from residential
      areas or places where children play outdoors, such as schools and parks. These
      measures may have beneficial effects in terms of reduced obesity formation in
      children.

PMID- 24913019
TI  - Exome sequencing reveals CHM mutations in six families with atypical
      choroideremia initially diagnosed as retinitis pigmentosa.
AB  - Mutations in almost 200 genes are associated with hereditary retinal diseases. Of
      these diseases, retinitis pigmentosa (RP) is the most common and is genetically
      and clinically highly heterogeneous. At least 62 genes are associated with RP and
      mutations in these genes account for approximately half of the cases of disease.
      In the present study, mutations in the CHM gene, which are known to associate
      with choroideremia, were identified in six of 157 families with retinitis
      pigmentosa by whole exome sequencing. No potential pathogenic mutations in the 62
      RP-associated genes were found in the six families. Sanger sequencing confirmed
      the mutations in CHM, including four novel (c.558_559delTT, c.964G>T, c.966delA,
      c.1166+2T>G) and two known (c.703-1G>A and c.1584_1587delTGTT) mutations.
      Available clinical data suggest an atypical phenotype of choroideremia in these
      patients compared to that of Caucasians. Overlapping clinical features and
      atypical phenotypic variation may contribute to the confusion of one another.
      Awareness of the phenotypic variation and careful clinical examination may
      facilitate proper clinical diagnosis and genetic counseling of complicated
      hereditary retinal diseases. Whole exome sequencing therefore is useful in the
      identification of genetic cause for less clarified hereditary retinal diseases
      and enriches our understanding of phenotypic variations of gene mutation.

PMID- 24913020
TI  - Dental emergencies presenting to a general hospital emergency department in
      Hobart, Australia.
AB  - BACKGROUND: Dental problems presenting to general hospital emergency departments
      (GHEDs) may create difficulties as there may not be appropriate facilities or
      personnel to manage them. The incidence and demographics of dental presentations
      to GHEDs in Tasmania are currently unexamined. This knowledge may be relevant in
      shaping dental service delivery. METHODS: The Emergency Department Information
      System (EDIS) at the Royal Hobart Hospital (RHH) was used to audit dental
      presentations through 2012. The presentations were analysed with respect to
      demographics and management. A literature review regarding dental presentations
      to GHEDs was also undertaken. RESULTS: Four hundred and fifty-four patient
      presentations to the RHH Emergency Department (ED) in 2012 were primarily of a
      dental nature, comprising 0.91% of all ED presentations. Sixty per cent of
      patients were male, and most were younger than 30 years. Dental abscesses and
      toothache accounted for 66%. Nine per cent of dental presentations (including 21%
      of infections) resulted in hospital admission. CONCLUSIONS: Dental infections
      contribute a significant burden of ED dental presentations. Encouraging and
      facilitating patients to seek timely and appropriate primary care from dentists
      may decrease the number of presentations to ED, and the drain on time and
      resources. Additionally, this may spare patients from the unpleasant experience
      of an acute dental infection episode.

PMID- 24913021
TI  - Editorial Comment from Dr Sato to Resiniferatoxin for treatment of lifelong
      premature ejaculation: a preliminary study.

PMID- 24913022
TI  - Systematic review and meta-analysis of Meniett therapy for Meniere's disease.
AB  - OBJECTIVES/HYPOTHESIS: To perform a systematic review and meta-analysis of
      micropressure treatment for Meniere's disease (MD). DATA SOURCES: Medline, Ovid,
      Web of Science, and Cochrane Library search of the literature from January 1996
      to December 2012. REVIEW METHODS: Systematic literature review followed Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion
      criteria required definitive diagnosis of unilateral MD, treatment with Meniett
      device, vertigo control results, and hearing results before and after treatment.
      Randomized controlled trials and other types of case-control studies were
      included. Improvements in vertigo, American Academy of Otolaryngology-Head and
      Neck Surgery (AAO-HNS) functional score, and pure tone average (PTA) were
      assessed. Funnel plots were used to detect bias and Q test was used to assess for
      heterogeneity. Random effects model was used for meta-analysis. T test was used
      to assess for significance. RESULTS: Of 113 abstracts screened, 18 studies met
      criteria for review and 12 were used for meta-analysis. Eight studies reported
      hearing evaluation and the improvement in PTA after Meniett treatment was
      significant (P = 0.0085). Data could not be combined for AAO-HNS functional score
      due to heterogeneity. However, there was a trend toward improvement. Of six
      studies reporting frequency of vertigo, Meniett treatment significantly reduced
      frequency of vertigo (P = < .0001). LIMITATIONS: Much of the data used in the
      analysis was derived from retrospective or level 4 studies. The average follow-up
      was only 5 months, and there were low number of patients in the treatment and
      control groups. CONCLUSION: The Meniett device is a safe, nondestructive
      treatment for patients' refractory to medical therapy for MD.

PMID- 24913023
TI  - Factors contributing to recurrence of oral cavity and laryngeal tumors and
      estimation of tumor age.
AB  - OBJECTIVES/HYPOTHESIS: To identify factors contributing to local tumor recurrence
      in oral cavity and laryngeal squamous cell carcinomas treated with surgery alone,
      to approximate tumor age from time to recurrence data by applying Collins' law,
      and to identify factors that may affect time to recurrence. STUDY DESIGN:
      Retrospective review. METHODS: A retrospective review of all patients treated for
      head and neck cancer from 1997 to 2013 at the University of Pittsburgh Medical
      Center was performed. RESULTS: A total of 517 patients treated with surgery alone
      qualified for the study, of which 84 had local recurrence, and 433 had no local
      recurrences. History of tobacco use (P = .017), pack-year cigarette history (P =
      .001), and T stage (P = .03) were associated with disease recurrence. Overall,
      never tobacco users, those with fewer pack-years of smoking history, and those
      with lower T stage were more likely to recur. Time to recurrence was
      significantly shorter for laryngeal tumors compared to oral cavity tumors (P =
      .027). Median time to recurrence for oral cavity tumors was 8.6 months and
      laryngeal tumors was 7.1 months. CONCLUSIONS: In this study, lower pack-year
      smoking history, lower T stage, and history of never tobacco use were associated
      with local tumor recurrence. Applying the concept of Collins' law to estimate the
      age of tumors at diagnosis, the median tumor age at diagnosis was estimated to be
      8.6 months for oral cavity tumors and 7.1 months for laryngeal tumors.

PMID- 24913024
TI  - Interference of Skp2 effectively inhibits the development and metastasis of colon
      carcinoma.
AB  - Colon cancer is a common type of malignancy in the digestive system. The aim of
      the present study was to investigate the role of S-phase kinase-associated
      protein 2 (Skp2) in colon carcinoma and to identify whether depletion of Skp2 by
      Skp2-RNA interference (RNAi) attenuates the proliferation and migration of colon
      carcinoma. Three pairs of small interfering (si)RNA were designed based on the
      Skp2 gene sequence and the most effective one was used to silence the Skp2 gene
      in SW620 cells. Subsequent to the interference, quantitative polymerase chain
      reaction and western blot analysis were used for detecting the expression of Skp
      2 mRNA and protein, respectively. The data demonstrated that the Skp2-siRNA
      effectively inhibited proliferation (P<0.01), increased the levels of apoptosis
      and induced G0/G1 phase arrest of the SW620 cells (P<0.01). Transfection of the
      Skp2 siRNA into SW620 cells effectively reduced Skp2 protein levels, while p27
      protein levels increased. In the in vivo experiments, a lentiviral vector of the
      Skp2-RNAi transfected into SW620 cells markedly inhibited Skp2 expression, as
      detected by immunohistochemical analysis of nude mice. Additionally,
      tumorigenicity experiments showed that inhibition of Skp2 significantly increased
      the survival rate of nude mice. Thus, the in vitro and in vivo results
      demonstrated that interference of Skp2 expression significantly inhibited the
      proliferation and induced the apoptosis of SW620 cells. This suggests that Skp2
      protein has an important role in the progression of colon cancer. Therefore, Skp2
      may enable the early diagnosis of colon cancer and provide new insights into
      molecular targets for cancer therapy. 

PMID- 24913025
TI  - Embryo catheter loading and embryo culture techniques: results of a worldwide Web
      based survey.
AB  - PURPOSE: To identify trends in embryo catheter loading and embryo culture
      techniques performed worldwide. METHODS: A retrospective evaluation using the
      results of a web-based survey, (IVF Worldwide ( www.IVF-worldwide.com ), was
      performed. RESULTS: Responses from 265 centers in 71 countries were obtained.
      Most centers (97 %) preferred a catheter with its orifice on top, with only 3 %
      preferring a catheter with the orifice on its side; 41 % preferred a catheter
      marked for clear ultrasound view. The most commonly-reported methods of embryo
      loading were medium-air-embryo-air-medium (42 %), medium in catheter with embryo
      at end (20 %) and medium-air-embryo (15 %). In 68 % of centers the final volume
      of the catheter was up to 0.3 ml, with only 19 % using 0.3-0.5 ml and 1 % using
      0.5-0.7 ml. Using reduced oxygen concentrations for embryo culture was divided
      between those who used it in combination with the two-gas system (34 %) and those
      who did not use it at all (39 %); 24 % reported using a three-gas system. Most
      clinics using reduced oxygen concentrations used it throughout the entire culture
      period. Half of centers (51 %) reported using reduced oxygen concentrations for
      the entire IVF population while 6 % reserved it only for blastocyst transfer. The
      use of sequential media was highly dominant with 40 % reporting its use.

PMID- 24913026
TI  - Association of glucose-6-phosphate dehydrogenase activity with oocyte cytoplasmic
      lipid content, developmental competence, and expression of candidate genes in a
      sheep model.
AB  - PURPOSE: To evaluate associations of glucose-6-phosphate dehydrogenase (G6PDH)
      activity in sheep oocytes with cytoplasmic lipid content, maturational
      competence, developmental competence to the blastocyst stage, and gene expression
      of certain molecular markers. METHODS: Before brilliant cresyl blue (BCB)
      staining test, oocytes were classified as high, middle, and low cytoplasmic lipid
      content (HCLC, MCLC, and LCLC) and after the test as having low or high G6PDH
      activity (BCB(+) and BCB(-), respectively). After maturation in vitro, a group of
      oocytes were subjected to IVF followed by in vitro embryo culture and another
      group was used for evaluation of expression of candidate genes. RESULTS: The
      cleavage and blastosyst rates were lowest (P < 0.05) in LCLC group, intermediate
      (P < 0.05) in MCLC group and highest (P < 0.05) in HCLC group. More (P < 0.05)
      oocytes in HCLC group were BCB(+), and higher (P < 0.05) maturation, cleavage,
      and blastocyst rates were seen for BCB(+) oocytes than the BCB(-) oocytes. Our
      gene expression data indicated that mRNA transcript abundance of ITGB2, pZP3,
      BMP15, and GDF9 genes was similar between BCB oocytes groups. However, the
      expression of ATP1A1 was higher (P < 0.05) for BCB(+) oocytes compared to BCB(-)
      oocytes. In addition, BAX transcript abundance was similar (P > 0.05) among
      BCB(+), BCB(-), and control groups, before and after maturation in vitro.
      CONCLUSION: Activity of G6PDH in sheep oocytes is highly associated with lipid
      content, and compared with the morphological parameters might be a more precise
      and objective predictor for subsequent developmental competence in vitro.

PMID- 24913027
TI  - Lack of association of KATNAL1 gene sequence variants and azoospermia in humans.
AB  - PURPOSE: A recent experiment indicated that a loss of function mutation in the
      murine Katnal1 gene resulted in male factor infertility due to premature
      exfoliation of spermatids. This study investigated the relevance of this gene to
      infertility in humans. METHODS: Multiple methods of genetic analysis were
      employed to investigate whether mutations in human KATNAL1 have a causative role
      in male infertility. This was a genetic association study, which included DNA
      samples from 105 men with non-obstructive azoospermia (NOA) and 242 anonymous
      sperm donor controls. 28 commercially available TaqMan SNP assays were used to
      haplotype samples from both groups and genetically tag regions of interest across
      the entire gene. AmpliSeq primers were then designed for identified regions so
      that targeted next-generation sequencing (NGS) could be used to identify
      causative variants. RESULTS: Four SNPs in the 3'UTR demonstrated a putative
      association with NOA. The AmpliSeq primers designed for the 3'UTR provided 83 %
      coverage of the 7,202 basepairs within the regions of interest. Variant sites
      were analyzed against genetic models to identify sequence polymorphisms which
      associated with NOA. No variants met standard criteria for significance when
      tested between the groups. CONCLUSIONS: This study suggests a lack of association
      of KATNAL1 gene sequence variants and azoospermia in humans.

PMID- 24913028
TI  - Educational backgrounds and quality of training of surgeons performing coronary
      artery bypass graft procedures in the state of Florida in 2010.
AB  - Quality of care is in part a result of the medical education practitioners
      receive. To date, little research has been conducted to assess the relationship
      between type, quantity, and quality of postgraduate residency and fellowship
      training and patient outcomes. This article explores the relationship of
      physician training and certification and surgical outcomes of patients undergoing
      coronary artery bypass grafting procedures in Florida during 2010. The data set
      includes 246 surgeons who, as a group, trained at nearly 48% of all thoracic
      surgery residency programs in the country. There were significant differences in
      board certifications for general surgery and thoracic surgery among physicians in
      different quality segmentations. Additionally, statistically significant
      differences were observed for mortality as a percentage of surgical volume as
      well as length of stay. These differences in characteristics and outcomes among
      segmentations of physicians warrant future exploration to identify underlying
      contributors to quality. 

PMID- 24913029
TI  - Exosomes in neurologic and psychiatric disorders.
AB  - PURPOSES: The purposes of this review were to discuss the role of exosomes in
      neurologic and psychiatric diseases and to propose future therapeutic approaches.
      METHODS: PubMed was searched (2000-2014) using the terms exosomes, microvesicles,
      neurological disorders, psychiatric disorders, multivesicular bodies, Alzheimer's
      disease, Parkinson's disease, prion disease, multiple sclerosis, schizophrenia,
      glioblastoma multiforme, and flavonoids. FINDINGS: Many cells of the nervous
      system have been reported to release exosomes that could have an active role in
      the function, development, and diseases of the CNS, such as Alzheimer disease,
      Parkinson disease, prion diseases, multiple sclerosis, brain tumors, and
      schizophrenia. In all of these diseases, exosomes are involved in the spread of
      "toxic" proteins that are mutated or "misfolded" and serve as templates for the
      formation of disease-producing oligomers. IMPLICATIONS: Exosomes' simple
      structure and abilities to be incorporated into plasma membrane and to cross the
      blood-brain barrier allow for the opportunity to utilize them as delivery
      vehicles of drugs and genetic elements in the treatment of immune, psychiatric,
      and neurologic disorders. Flavonoids have emerged as unique, natural molecules
      with antioxidant and antiinflammatory properties. It would, therefore, be of
      interest to design flavonoid-containing exosomes.

PMID- 24913030
TI  - Adherence to premixed insulin in a prefilled pen compared with a vial/syringe in
      people with diabetes in Singapore.
AB  - BACKGROUND: The real-world clinical effectiveness of exogenous insulin is limited
      by nonadherence. Various insulin delivery systems have been developed to help
      improve adherence, with prefilled pens gaining popularity among adult
      Singaporeans with diabetes. However, adherence to insulin in people with diabetes
      in Singapore and most of Asia has not been studied. OBJECTIVES: This study aimed
      to compare adherence to premixed insulin formulated in a prefilled pen versus a
      vial/syringe and to identify predictors of adherence in 955 patients managed at
      the outpatient clinics of the largest acute care hospital in Singapore. METHODS:
      In this retrospective longitudinal study, electronic medical and pharmacy refill
      records were used to determine adherence to insulin over 24 months, measured in
      terms of compliance and persistence. Compliance is expressed as the medication
      possession ratio (used as continuous and categorical variables), and persistence
      is reported as a dichotomous variable with a permissible refill gap of 30 days
      before discontinuation of therapy is considered. Multivariate linear or logistic
      regression analysis was used to identify predictors of adherence. RESULTS:
      Compared with prefilled pen users, vial/syringe users were older (mean [SD] age,
      64.1 [10.6] vs 62.4 [11.9] years; P = 0.032), and more were undergoing
      polypharmacy (69.6% vs 54.1%; P < 0.001). The mean (SD) medication possession
      ratio was comparable in vial/syringe versus prefilled pen users (83.8% [26.9%] vs
      86.0% [23.2%]; P = 0.266). Prefilled pen users were more persistent with therapy
      compared with vial/syringe users (odds ratio = 1.36; 95% CI, 1.01-1.86) after
      adjusting for sociodemographic and clinical covariates. Median time to
      discontinuation of therapy was comparable (vial/syringe vs prefilled pen: 409 vs
      532 days; P = 0.076). Being managed by an endocrinologist and not receiving
      government subsidies were significant predictors of persistence. CONCLUSIONS:
      Compared with other studies that found strong associations between adherence and
      insulin devices, the findings of this study suggest that persistence but not
      compliance varies by insulin device. The willingness to pay for health care, in
      addition to affordability, may affect insulin therapy adherence. Patients with
      uncontrolled diabetes due to suspected nonadherence may benefit from referral to
      a multidisciplinary care team comprising endocrinologists, diabetes nurse
      educators, dietitians, and allied health professionals. These findings are
      applicable to outpatients with similar demographic features managed at other
      acute care hospitals in Singapore. The impact of insulin devices on glycemic
      control needs to be investigated in future larger studies.

PMID- 24913031
TI  - Meta-analysis of Methylenetetrahydrofolate reductase maternal gene in Down
      syndrome: increased susceptibility in women carriers of the MTHFR 677T allele.
AB  - Because a number of data studies include some controversial results about
      Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Down syndrome (DS),
      we performed a meta-analysis to determine a more precise estimation of this
      association. Studies were searched on PubMed, EMBASE and Lilacs-Scielo, up to
      April 2013, and they were eligible if they included case mothers (DSM) that have
      gave birth to children with DS, and controls mothers (CM) that have gave birth to
      healthy children without chromosomal abnormality, syndrome or malformation. The
      combined odds ratio with 95% confidence intervals was calculated by fixed or
      random effects models to assess the strength of associations. Potential sources
      of heterogeneity between studies were evaluated using Q test and the I(2).
      Publication bias was estimated using Begg's test and Egger's linear regression
      test. Sensitivity analyses were performed by using allelic, dominant, recessive
      and codominant genetic models, Hardy-Weinberg equilibrium (HWE) and ethnicity.
      Twenty-two studies with 2,223 DSM and 2,807 CM were included for MTHFR C677T and
      15 studies with 1,601 DSM and 1,849 CM were included for MTHFR A1298C. Overall
      analysis suggests an association of the MTHFR C677T polymorphism with maternal
      risk for DS. Moreover, no association between the MTHFR A1298C polymorphism and
      maternal risk for DS was found. There is also evidence of higher heterogeneity,
      with I(2) test values ranging from 8 to 89%. No evidence of publication bias was
      found. Taken together, our meta-analysis implied that the T allele carriers might
      carry an increased maternal risk for DS.

PMID- 24913032
TI  - Integrated microRNA-mRNA analysis of coronary artery disease.
AB  - Although patients with coronary artery disease (CAD) have a high mortality rate,
      the pathogenesis of CAD is still poorly understood. The purpose of this study was
      to explore the underlying molecular mechanisms and potential target molecules for
      CAD. The platelet miRNA (GSE28858) and blood mRNA (GSE42148) expression profiles
      of patients with CAD and healthy controls were downloaded from Gene Expression
      Omnibus. Differentially expressed miRNAs and genes (DEGs) were identified by
      significant analysis of microarray algorithm after data preprocessing.
      Furthermore, the miRNA-target gene regulatory network was constructed based on
      miRecords database. The spearman correlation coefficients (rho) between miRNAs
      and their target genes were calculated. Six up- (miR-340, miR-545, miR-451,
      miR454-5p, miR-624 and miR-585) and four down-regulated (miR-199a, miR-17-3p, miR
      154 and miR-339) miRNAs were screened. Total 295 target genes of miR-545, miR
      451, miR-585 and miR-154 were predicted. Among these 295 target genes, 7 genes
      were DEGs. Further analysis showed miR-545-TFEC and miR-585-SPOCK1 were highly
      positively correlated (rho = 0.808091264; rho = 0.874680776) in CAD samples.
      Therefore, differentially expressed miRNAs might participate in the pathogenesis
      of CAD by regulating their target genes.

PMID- 24913033
TI  - Expanding the repertoire of microsatellite markers for polymorphism studies in
      Indian accessions of mung bean (Vigna radiata L. Wilczek).
AB  - Limited availability of validated, polymorphic microsatellite markers in mung
      bean (Vigna radiata), an important food legume of India, has been a major hurdle
      towards its improvement and higher yield. The present study was undertaken in
      order to develop a new set of microsatellite markers and utilize them for the
      analysis of genetic diversity within mung bean accessions from India. A GA/CT
      enriched library was constructed from V. radiata which resulted in 1,250 putative
      recombinant clones of which 850 were sequenced. SSR motifs were identified and
      their flanking sequences were utilized to design 328 SSR primer pairs. Of these,
      48 SSR markers were employed for assessing genetic diversity among 76 mung bean
      accessions from various geographical locations in India. Two hundred and thirty
      four alleles with an average of 4.85 alleles per locus were detected at 48 loci.
      The polymorphic information content (PIC) per locus varied from 0.1 to 0.88
      (average: 0.49 per locus). The observed and expected heterozygosities ranged from
      0.40 to 0.95 and 0.40 to 0.81 respectively. Based on Jaccard's similarity matrix,
      a dendrogram was constructed using the unweighted pair-group method with
      arithmetic averages (UPGMA) analysis which revealed that one accession from
      Bundi, Rajasthan was clustered out separately while remaining accessions were
      grouped into two major clusters. The markers generated in this study will help in
      expanding the repertoire of the available SSR markers thereby facilitating
      analysis of genetic diversity, molecular mapping and ultimately broadening the
      scope for genetic improvement of this legume.

PMID- 24913034
TI  - Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in
      gastric cancer metastasis.
AB  - miRNAs have emerged as crucial regulators in the regulation of development as
      well as human diseases, especially tumorigenesis. The aims of this study are to
      evaluate miR-30b-5p expression pattern and mechanism in gastric carcinogenesis
      due to which remains to be determined. Expression of miR-30b-5p was analyzed in
      51 gastric cancer cases and 4 cell lines by qRT-PCR. The effect of DNA
      methylation on miR-30b-5p expression was assessed by MSP and BGS. In order to
      know whether DNMT1 increased miR-30b-5p promoter methylation, DNMT1 was depleted
      in cell lines AGS and BGC-823. The role of miR-30b-5p on cell migration was
      evaluated by wound healing assays. Decreased expression of miR-30b-5p was found
      in gastric cancer samples. In tumor, the expression level of miR-30b-5p was
      profound correlated with lymph node metastasis (P = 0.019). The level of miR-30b
      5p may be restored by DNA demethylation and DNMT1 induced miR-30b-5p promoter
      methylation. In vitro functional assays implied that enforced miR-30b-5p
      expression affected cell migration, consistent with tissues analysis. Our
      findings uncovered that miR-30b-5p is significantly diminished in gastric cancer
      tissues, providing the first insight into the epigenetic mechanism of miR-30b-5p
      down-regulation, induced by DNMT1, and the role of miR-30b-5p in gastric cancer
      carcinogenesis. Overexpression of miR-30b-5p inhibited cell migration. Thus, miR
      30b-5p may represent a potential therapeutic target for gastric cancer therapy.

PMID- 24913035
TI  - Osseointegration of acellular and cellularized osteoconductive scaffolds: is
      tissue engineering using mesenchymal stem cells necessary for implant fixation?
AB  - The main issue associated with revision total hip replacements (rTHRs) is how to
      generate new bone adjacent to implants and achieve fixation of the revision
      implant. In its simplest form, bone tissue engineering (BTE) combines cells and
      scaffolds in vitro to replace damaged or lost bone in vivo. Our aim was to
      develop BTE porous TiAl6V4 constructs with a calcium-phosphate coating without or
      with mesenchymal stem cells (MSCs) seeded throughout the entire porous structure
      to enhance new bone formation and which could be used for rTHRs. Porous titanium
      scaffolds made by selective laser sintering were seeded throughout with
      autologous bone marrow MSCs and cultured in a perfusion bioreactor. Constructs
      were implanted in the medial femoral condyle of 20 skeletally mature mule sheep
      with and without a gap of 2.5 mm between the construct and the host bone. After 6
      weeks, the addition of MSCs to the scaffolds did not significantly increase
      osseointegration or implant-bone fixation strength. However, in the defects with
      a gap, the cellularized constructs showed higher implant-bone contact area and
      implant-bone fixation strength. BTE can be applied to develop acellular or
      cellularized constructs with clinical application in rTHRs where a lack of bone
      stock is problematic.

PMID- 24913036
TI  - Takotsubo cardiomyopathy following acute liver failure.

PMID- 24913038
TI  - Exposure to secondhand smoke and voluntary adoption of smoke-free home and car
      rules among non-smoking South African adults.
AB  - BACKGROUND: Secondhand smoke (SHS) exposure is a well-established health hazard.
      To determine the effectiveness of existing smoke-free policies and adoption of
      smoke-free rules in South Africa, we assessed exposure to SHS from several
      sources among non-smoking adults during 2010. METHODS: Data were analyzed for
      3,094 adults aged >=16 years who participated in the 2010 South African Social
      Attitudes Survey. Descriptive statistics and multivariate analyses were used to
      assess presence of smoke-free rules among all South Africans, and prevalence and
      correlates of SHS exposure at work, at home, and at hospitality venues among non
      smokers. RESULTS: Overall, 70.6% of all South African adults had 100% smoke-free
      rules in their private cars, 62.5% in their homes, while 63.9% worked in places
      with 100% smoke-free policies. Overall, 55.9% of all non-smokers reported
      exposure to SHS from at least one source (i.e., in the home, workplace or at a
      hospitality venue). By specific source of exposure, 18.4% reported being exposed
      to SHS at work, 25.2% at home, 33.4% in a restaurant, and 32.7% at a bar.
      Presence of work bans on indoor smoking conferred lower likelihood of SHS
      exposure at work among non-smokers (adjusted odds ratio [aOR] = 0.23; 95% CI:
      0.09-0.60). Similarly, smoke-free home rules decreased the odds of being exposed
      to SHS at home among non-smokers (aOR =0.16; 95% CI: 0.09-0.30). CONCLUSION: Over
      half of South African adults reported SHS exposure in the home or at public
      places such as the workplace and at hospitality venues. This underscores the need
      for comprehensive smoke-free laws that prohibit smoking in all public indoor
      areas without exemptions.

PMID- 24913037
TI  - The transcriptional responsiveness of LKB1 to STAT-mediated signaling is
      differentially modulated by prolactin in human breast cancer cells.
AB  - BACKGROUND: Liver kinase 1 (LKB1) is an important multi-tasking protein linked
      with metabolic signaling, also controlling polarity and cytoskeletal
      rearrangements in diverse cell types including cancer cells. Prolactin (PRL) and
      Signal transducer and activator of transcription (STAT) proteins have been
      associated with breast cancer progression. The current investigation examines the
      effect of PRL and STAT-mediated signaling on the transcriptional regulation of
      LKB1 expression in human breast cancer cells. METHODS: MDA-MB-231, MCF-7, and
      T47D human breast cancer cells, and CHO-K1 cells transiently expressing the PRL
      receptor (long form), were treated with 100 ng/ml of PRL for 24 hours. A LKB1
      promoter-luciferase construct and its truncations were used to assess
      transcriptional changes in response to specific siRNAs or inhibitors targeting
      Janus activated kinase 2 (JAK2), STAT3, and STAT5A. Real-time PCR and Western
      blotting were applied to quantify changes in mRNA and protein levels.
      Electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP)
      assays were used to examine STAT3 and STAT5A binding to the LKB1 promoter.
      RESULTS: Consistent with increases in mRNA, the LKB1 promoter was up-regulated by
      PRL in MDA-MB-231 cells, a response that was lost upon distal promoter
      truncation. A putative GAS element that could provide a STAT binding site mapped
      to this region, and its mutation decreased PRL-responsiveness. PRL-mediated
      increases in promoter activity required signaling through STAT3 and STAT5A, also
      involving JAK2. Both STATs imparted basally repressive effects in MDA-MB-231
      cells. PRL increased in vivo binding of STAT3, and more definitively, STAT5A, to
      the LKB1 promoter region containing the GAS site. In T47D cells, PRL down
      regulated LKB1 transcriptional activity, an effect that was reversed upon culture
      in phenol red-free media. Interleukin 6, a cytokine activating STAT signaling in
      diverse cell types, also increased LKB1 mRNA levels and promoter activity in MDA
      MB-231 cells. CONCLUSIONS: LKB1 is differentially regulated by PRL at the level
      of transcription in representative human breast cancer cells. Its promoter is
      targeted by STAT proteins, and the cellular estrogen receptor status may affect
      PRL-responsiveness. The hormonal and possibly cytokine-mediated control of LKB1
      expression is particularly relevant in aggressive breast cancer cells,
      potentially promoting survival under energetically unfavorable conditions.

PMID- 24913039
TI  - Prenatal diagnosis of giant cardiac rhabdomyoma in tuberous sclerosis complex: a
      new therapeutic option with everolimus.
AB  - Tuberous sclerosis complex (TSC) is a genetic disorder characterized by abnormal
      cell proliferation and tumor growth in a number of organ systems, primarily the
      brain, kidneys, eyes and heart. Clinical symptoms vary according to the location
      of the tumor. The most common disorders are seizures, neurodevelopmental
      disorders, renal failure and arrhythmias. TSC was found to be influenced by
      inhibitors of the protein kinase mammalian target of rapamycin (mTOR), which
      regulates abnormal cellular proliferation. mTOR inhibitors have been studied
      effectively in patients with subependymal giant-cell astrocytomas and renal
      angiolipomas in the context of TSC. We describe a prenatally diagnosed case of
      giant rhabdomyoma, due to right ventricular outflow tract obstruction, which
      presented as a duct-dependent lesion. Postnatal treatment with the mTOR inhibitor
      everolimus initiated significant regression of the cardiac tumor. This finding
      suggests that mTOR inhibitor therapy is an option for giant rhabdomyomas that
      develop in the neonatal period.

PMID- 24913040
TI  - Attitudes to mesalamine questionnaire: a novel tool to predict mesalamine
      nonadherence in patients with IBD.
AB  - OBJECTIVES: Poor adherence to mesalamine is common and driven by a combination of
      lifestyle and behavioral factors, as well as health beliefs. We sought to develop
      a valid tool to identify barriers to patient adherence and predict those at risk
      for future nonadherence. METHODS: A 10-item survey was developed from patient
      reported barriers to adherence. The survey was administered to 106 patients with
      ulcerative colitis who were prescribed mesalamine, and correlated with
      prospectively collected 12-month pharmacy refills (medication possession ratio
      (MPR)), urine levels of salicylates, and self-reported adherence (Morisky
      Medication Adherence Scale (MMAS)-8). RESULTS: From the initial 10-item survey, 8
      items correlated highly with the MMAS-8 score at enrollment. Computer-generated
      randomization produced a derivation cohort of 60 subjects and a validation cohort
      of 46 subjects to assess the survey items in their ability to predict future
      adherence. Two items from the patient survey correlated with objective measures
      of long-term adherence: their belief in the importance of maintenance mesalamine
      even when in remission and their concerns about side effects. The additive score
      based on these two items correlated with 12-month MPR in both the derivation and
      validation cohorts (P<0.05). Scores on these two items were associated with a
      higher risk of being nonadherent over the subsequent 12 months (relative risk
      (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for
      the performance of this 2-item tool was greater than that of the 10-item MMAS-8
      score for predicting MPR scores over 12 months (area under the curve 0.7 vs.
      0.5). CONCLUSIONS: Patients' beliefs about the need for maintenance mesalamine
      and their concerns about side effects influence their adherence to mesalamine
      over time. These concerns could easily be raised in practice to identify patients
      at risk of nonadherence (Clinical Trial number NCT01349504).

PMID- 24913041
TI  - Development of an algorithm incorporating pharmacokinetics of adalimumab in
      inflammatory bowel diseases.
AB  - OBJECTIVES: Several decision algorithms based on the measurement of infliximab
      (IFX) trough levels and antibodies to IFX have been proposed. Whether such
      algorithms can be extrapolated to the pharmacokinetics of adalimumab (ADA) has
      yet to be determined. METHODS: A prospective study included all consecutive
      patients with inflammatory bowel disease (IBD) having a disease flare while being
      on ADA 40 mg every 2 weeks were included. All patients were primary responders to
      ADA therapy and were anti-tumor necrosis factor (TNF) naive. ADA trough levels
      and antibodies against ADA (AAA) were measured blinded to clinical data (Elisa
      LISA-Tracker, Theradiag). All patients were optimized with ADA 40 mg weekly. Four
      months later, in the absence of clinical remission (CR; Crohn's disease activity
      index <150 for Crohn's disease (CD), and Mayo score <2 for ulcerative colitis),
      patients were treated with IFX therapy. Patients were divided into three groups
      based on ADA trough levels and based on previous studies: group A, ADA>4.9
      MUg/ml; group B, ADA<4.9 MUg/ml and undetectable levels of AAA (<10 ng/ml); and
      group C, ADA<4.9 MUg/ml and AAA >10 ng/ml. RESULTS: A total of 82 patients were
      included (55% CD; mean age=43 years, disease duration=7.4 years, duration of ADA
      therapy=17 months). After optimization of ADA treatment, 29.2% of patients
      achieved CR in group A (N=41), 67% in group B (N=24), and 12% in group C (N=17;
      P<0.01 between groups A/B and B/C). C-reactive protein level at the time of
      relapse, disease duration, duration of ADA therapy, and IBD type was not
      predictive of CR after ADA optimization by univariate analysis. The response to
      ADA optimization was significantly more durable in group B (15 months) than in
      groups A and C (4 and 5 months, respectively). Fifty-two patients who failed
      following ADA optimization (63%) were treated with IFX, and 30.6% of them
      achieved CR. CR rates following IFX initiation were 6.9%, 25%, and 80% in groups
      A, B, and C, respectively (P<0.01 between groups C/A and between groups C/B).
      Duration of response to IFX was significantly higher in group C than in groups A
      and B (14 vs. 3 and 5 months, respectively, P<0.01). CONCLUSIONS: The presence of
      low ADA trough levels without AAA is strongly predictive of clinical response in
      67% of cases after ADA optimization. Conversely, low ADA levels with detectable
      AAA are associated with ADA failure, and switching to IFX should be considered.
      ADA trough levels >4.9 MUg/ml are associated with failure of two anti-TNF agents
      (ADA and IFX) in 90% of cases, and switching to another drug class should be
      considered.

PMID- 24913042
TI  - Sphere of influence of indole acetic acid and nitric oxide in bacteria.
AB  - Bacterial biosynthesis of the phytohormone, indole-3-acetic acid (IAA) is well
      established and along with the diffusible gaseous molecule, nitric oxide (NO) is
      known to positively regulate the developmental processes of plant roots. IAA and
      NO act as signaling molecules in plant-microbe interactions as they modulate the
      gene expression in both, plants and microorganisms. Although IAA and NO may not
      be required for essential bacterial physiological processes, numerous studies
      point towards a crosstalk between IAA and NO in the rhizosphere. In this review,
      we describe various IAA and NO-responsive or sensing genes/proteins/regulators.
      There is also growing evidence for the interaction of IAA and NO with other plant
      growth regulators and the involvement of NO with the quorum sensing system in
      biofilm formation and virulence. This interactive network can greatly impact the
      host plant-microbe interactions in the soil. Coupled with this, the specialized
      sigma(54) -dependent transcription observed in some of the IAA and NO-influenced
      genes can confer inducibility to these traits in bacteria and may allow the
      expression of IAA and NO-influenced microbial genes in nutrient limiting or
      changing environmental conditions for the benefit of plants. 

PMID- 24913043
TI  - Association between Physician Orders for Life-Sustaining Treatment for Scope of
      Treatment and in-hospital death in Oregon.
AB  - OBJECTIVES: To examine the relationship between Physician Orders for Life
      Sustaining Treatment (POLST) for Scope of Treatment and setting of care at time
      of death. DESIGN: Cross-sectional. SETTING: Oregon in 2010 and 2011.
      PARTICIPANTS: People who died of natural causes. MEASUREMENTS: Oregon death
      records containing cause and location of death were matched with POLST orders for
      people with a POLST form in the Oregon POLST registry. Logistic regression was
      used to measure the association between POLST orders and location of death.
      RESULTS: Of 58,000 decedents, 17,902 (30.9%) had a POLST form in the registry.
      Their orders for Scope of Treatment were comfort measure only, 11,836 (66.1%);
      limited interventions, 4,787 (26.7%); and full treatment, 1,153 (6.4%). Comfort
      measures only (CMO) orders advise avoiding hospitalization unless comfort cannot
      be achieved in the current setting; 6.4% of participants with POLST CMO orders
      died in the hospital, compared with 44.2% of those with orders for full treatment
      and 34.2% for those with no POLST form in the registry. In the logistic
      regression, the odds of dying in the hospital of those with an order for limited
      interventions was 3.97 times as great (95% CI = 3.59-4.39) as of those with a CMO
      order, and the odds of those with an order for full treatment was 9.66 times as
      great (95% CI = 8.39-11.13). CONCLUSIONS: The association with numbers of deaths
      in the hospital suggests that end-of-life preferences of people who wish to avoid
      hospitalization as documented in POLST orders are honored.

PMID- 24913044
TI  - Two novel phytotoxic substances from Leucas aspera.
AB  - Leucas aspera (Lamiaceae), an aromatic herbaceous plant, is well known for many
      medicinal properties and a number of bioactive compounds against animal cells
      have been isolated. However, phytotoxic substances from L. aspera have not yet
      been documented in the literature. Therefore, current research was conducted to
      explore the phytotoxic properties and substances in L. aspera. Aqueous methanol
      extracts of L. aspera inhibited the germination and growth of garden cress
      (Lepidum sativum) and barnyard grass (Echinochloa crus-galli), and the inhibitory
      activities were concentration dependent. These results suggest that the plant may
      have phytotoxic substances. The extracts were then purified by several
      chromatographic runs. The final purification was achieved by reversed-phase HPLC
      to give an equilibrium (or inseparable) 3:2 mixture of two labdane type
      diterpenes (compounds 1 and 2). These compounds were characterized as (rel
      5S,6R,8R,9R,10S,13S,15S,16R)-6-acetoxy-9,13;15,16-diepoxy-15-hydroxy-16
      methoxylabdane (1) and (rel 5S,6R,8R,9R,10S,13S,15R,16R)-6-acetoxy-9,13;15,16
      diepoxy-15-hydroxy-16-methoxylabdane (2) by spectroscopic analyses. A mixture of
      the two compounds inhibits the germination and seedling growth of garden cress
      and barnyard grass at concentrations greater than 30 and 3 MUM, respectively. The
      concentration required for 50% growth inhibition (I50) of the test species ranges
      from 31 to 80 MUM, which suggests that the mixture of these compounds, are
      responsible for the phytotoxic activity of L. aspera plant extract.

PMID- 24913045
TI  - ACC deaminase-containing Arthrobacter protophormiae induces NaCl stress tolerance
      through reduced ACC oxidase activity and ethylene production resulting in
      improved nodulation and mycorrhization in Pisum sativum.
AB  - Induction of stress ethylene production in the plant system is one of the
      consequences of salt stress which apart from being toxic to the plant also
      inhibits mycorrhizal colonization and rhizobial nodulation by oxidative damage.
      Tolerance to salinity in pea plants was assessed by reducing stress ethylene
      levels through ACC deaminase-containing rhizobacteria Arthrobacter protophormiae
      (SA3) and promoting plant growth through improved colonization of beneficial
      microbes like Rhizobium leguminosarum (R) and Glomus mosseae (G). The experiment
      comprised of treatments with combinations of SA3, G, and R under varying levels
      of salinity. The drop in plant biomass associated with salinity stress was
      significantly lesser in SA3 treated plants compared to non-treated plants. The
      triple interaction of SA3+G+R performed synergistically to induce protective
      mechanism against salt stress and showed a new perspective of plant-microorganism
      interaction. This tripartite collaboration increased plant weight by 53%, reduced
      proline content, lipid peroxidation and increased pigment content under 200 mM
      salt condition. We detected that decreased ACC oxidase (ACO) activity induced by
      SA3 and reduced ACC synthase (ACS) activity in AMF (an observation not reported
      earlier as per our knowledge) inoculated plants simultaneously reduced the ACC
      content by 60% (responsible for generation of stress ethylene) in SA3+G+R treated
      plants as compared to uninoculated control plants under 200 mM salt treatment.
      The results indicated that ACC deaminase-containing SA3 brought a putative
      protection mechanism (decrease in ACC content) under salt stress, apart from
      alleviating ethylene-induced damage, by enhancing nodulation and AMF colonization
      in the plants resulting in improved nutrient uptake and plant growth.

PMID- 24913046
TI  - Stress enhances the gene expression and enzyme activity of phenylalanine ammonia
      lyase and the endogenous content of salicylic acid to induce flowering in
      pharbitis.
AB  - The involvement of salicylic acid (SA) in the regulation of stress-induced
      flowering in the short-day plant pharbitis (also called Japanese morning glory)
      Ipomoea nil (formerly Pharbitis nil) was studied. Pharbitis cv. Violet was
      induced to flower when grown in 1/100-strength mineral nutrient solution under
      non-inductive long-day conditions. All fully expanded true leaves were removed
      from seedlings, leaving only the cotyledons, and flowering was induced under poor
      nutrition stress conditions. This indicates that cotyledons can play a role in
      the regulation of poor-nutrition stress-induced flowering. The expression of the
      pharbitis homolog of PHENYLALANINE AMMONIA-LYASE, the enzyme activity of
      phenylalanine ammonia-lyase (PAL; E.C. 4.3.1.5) and the content of SA in the
      cotyledons were all up-regulated by the stress treatment. The Violet was also
      induced to flower by low-temperature stress, DNA demethylation and short-day
      treatment. Low-temperature stress enhanced PAL activity, whereas non-stress
      factors such as DNA demethylation and short-day treatment decreased the activity.
      The PAL enzyme activity was also examined in another cultivar, Tendan, obtaining
      similar results to Violet. The exogenously applied SA did not induce flowering
      under non-stress conditions but did promote flowering under weak stress
      conditions in both cultivars. These results suggest that stress-induced flowering
      in pharbitis is induced, at least partly, by SA, and the synthesis of SA is
      promoted by PAL. 

PMID- 24913047
TI  - The presence of soluble carbonic anhydrase in the thylakoid lumen of chloroplasts
      from Arabidopsis leaves.
AB  - Supernatant obtained after high-speed centrifugation of disrupted thylakoids that
      had been washed free from extrathylakoid carbonic anhydrases demonstrated
      carbonic anhydrase activity that was inhibited by the specific inhibitors
      acetazolamide and ethoxyzolamide. A distinctive feature of the effect of Triton X
      100 on this activity also suggested that the source of the activity is a soluble
      protein. Native electrophoresis of a preparation obtained using chromatography
      with agarose/mafenide as an affinity sorbent revealed one protein band with
      carbonic anhydrase activity. The same protein was revealed in a mutant deficient
      in soluble stromal carbonic anhydrase beta-CA1, and this indicated that the newly
      revealed carbonic anhydrase is not a product of the At3g01500 gene. These data
      imply the presence of soluble carbonic anhydrase in the thylakoid lumen of higher
      plants. 

PMID- 24913048
TI  - The dihydrolipoyl acyltransferase gene BCE2 participates in basal resistance
      against Phytophthora infestans in potato and Nicotiana benthamiana.
AB  - Dihydrolipoyl acyltransferase (EC 2.3.1.12), a branched-chain alpha-ketoacid
      dehydrogenase E2 subunit (BCE2), catalyzes the transfer of the acyl group from
      the lipoyl moiety to coenzyme A. However, the role of BCE2 responding to biotic
      stress in plant is not clear. In this study, we cloned and characterized a BCE2
      gene from potato, namely StBCE2, which was previously suggested to be involved in
      Phytophthora infestans-potato interaction. We found that the expression of StBCE2
      was strongly induced by both P. infestans isolate HB09-14-2 and salicylic acid.
      Besides, when the homolog of StBCE2 in Nicotiana benthamiana named NbBCE2 was
      silenced, plants showed increased susceptibility to P. infestans and reduced
      accumulation of hydrogen peroxide (H2O2). Furthermore, we found that a marker
      gene NbrbohB involved in the production of reactive oxygen species, was also
      suppressed in NbBCE2-silenced plants. However, silencing of NbBCE2 had no
      significant effect on the hypersensitive responses trigged by INF1, R3a-AVR3a(KI)
      pair or Rpi-vnt1.1-AVR-vnt1.1 pair. Our results suggest that BCE2 is associated
      with the basal resistance to P. infestans by regulating H2O2 production. 

PMID- 24913049
TI  - Characterization and responses to environmental cues of a photosynthetic antenna
      deficient mutant of the filamentous cyanobacterium Anabaena sp. PCC 7120.
AB  - The cyanobacterial phycobilisome (PBS) is a giant pigment-protein complex which
      harvests light energy for photosynthesis and comprises two structures: a core and
      peripheral rods. Most studies on PBS structure and function are based on mutants
      of unicellular strains. In this report, we describe the phenotypic and genetic
      characterization of a transposon mutant of the filamentous Anabaena sp. strain
      PCC 7120, denoted LC1, which cannot synthesize the phycobiliprotein phycocyanin
      (PC), the main component of the rods; in this mutant, the transposon had inserted
      into the cpcB gene (orf alr0528) which putatively encodes PC-beta chain. Mutant
      LC1 was able to synthesize phycoerythrocyanin (PEC), a phycobiliprotein (PBP)
      located at the terminal region of the rods; but in the absence of PC, PEC did not
      attach to the PBSs that only retained the allophycocyanin (APC) core; ferredoxin:
      NADP+-oxidoreductase (FNR) that is associated with the PBS in the wild type, was
      not found in isolated PBSs from LC1. The performance of the mutant exposed to
      different environmental conditions was evaluated. The mutant phenotype was
      successfully complemented by cloning and transfer of the wild type complete cpc
      operon to mutant LC1. Interestingly, LC1 compensated its mutation by
      significantly increasing the number of its core-PBS and the effective quantum
      yield of photosystem II (PSII) photochemistry; this feature suggests a more
      efficient energy conversion in the mutant which may be useful for
      biotechnological applications.

PMID- 24913050
TI  - Treatment of Amaranthus cruentus with chemical and biological inducers of
      resistance has contrasting effects on fitness and protection against compatible
      Gram positive and Gram negative bacterial pathogens.
AB  - Amaranthus cruentus (Ac) plants were treated with the synthetic systemic acquired
      resistance (SAR) inducer benzothiadiazole (BTH), methyl jasmonate (MeJA) and the
      incompatible pathogen, Pseudomonas syringae pv. syringae (Pss), under greenhouse
      conditions. The treatments induced a set of marker genes in the absence of
      pathogen infection: BTH and Pss similarly induced genes coding for pathogenesis
      related and antioxidant proteins, whereas MeJA induced the arginase, LOX2 and
      amarandin 1 genes. BTH and Pss were effective when tested against the Gram
      negative pathogen Ps pv. tabaci (Pst), which was found to have a compatible
      interaction with grain amaranth. The resistance response appeared to be salicylic
      acid-independent. However, resistance against Clavibacter michiganensis subsp.
      michiganensis (Cmm), a Gram positive tomato pathogen also found to infect Ac, was
      only conferred by Pss, while BTH increased susceptibility. Conversely, MeJA was
      ineffective against both pathogens. Induced resistance against Pst correlated
      with the rapid and sustained stimulation of the above genes, including the AhPAL2
      gene, which were expressed both locally and distally. The lack of protection
      against Cmm provided by BTH, coincided with a generalized down-regulation of
      defense gene expression and chitinase activity. On the other hand, Pss-treated Ac
      plants showed augmented expression levels of an anti-microbial peptide gene and,
      surprisingly, of AhACCO, an ethylene biosynthetic gene associated with
      susceptibility to Cmm in tomato, its main host. Pss treatment had no effect on
      productivity, but compromised growth, whereas MeJA reduced yield and harvest
      index. Conversely, BTH treatments led to smaller plants, but produced
      significantly increased yields. These results suggest essential differences in
      the mechanisms employed by biological and chemical agents to induce SAR in Ac
      against bacterial pathogens having different infection strategies. This may
      determine the outcome of a particular plant-pathogen interaction, leading to
      resistance or susceptibility, as in Cmm-challenged Ac plants previously induced
      with Pss or BTH, respectively. 

PMID- 24913051
TI  - Multistep involvement of glutathione with salicylic acid and ethylene to combat
      environmental stress.
AB  - The role of glutathione (GSH) in plant defense is an established fact. However,
      the association of GSH with other established signaling molecules within the
      defense signaling network remains to be evaluated. Previously we have shown that
      GSH is involved in defense signaling network likely through NPR1-dependent
      salicylic acid (SA)-mediated pathway. In this study, to gain further insight, we
      developed chloroplast-targeted gamma-glutamylcysteine synthetase (gamma-ECS)
      overexpressed transgenic Nicotiana tabacum (NtGp line) and constructed a forward
      subtracted cDNA (suppression subtractive hybridization (SSH)) library using NtGp
      line as a tester. Interestingly, in addition to SA-related transcripts like
      pathogenesis-related protein 1a (PR1a) and SAR8.2 m/2l, 1-aminocyclopropane-1
      carboxylate oxidase (ACC oxidase), a key enzyme of ethylene (ET) biosynthesis,
      was identified in the SSH library. Besides, transcription factors like WRKY
      transcription factor 3 (WRKY3), WRKY1 and ethylene responsive factor 4 (ERF4),
      associated with SA and ET respectively, were also identified thus suggesting an
      interplay of GSH with ET and SA. Furthermore, proteomic profiling of NtGp line,
      performed by employing two-dimensional gel electrophoresis (2-DE), corroborated
      with the transcriptomic profile and several defense-related proteins like
      serine/threonine protein kinase, and heat shock 70 protein (HSP70) were
      identified with increased accumulation. Fascinatingly, induction of 1
      aminocyclopropane-1-carboxylate synthase (ACC synthase) was also noted thus
      demonstrating the active involvement of GSH with ET. Protein gel blot analysis
      confirmed the enhanced accumulation of ACC oxidase in NtGp line. Together, our
      data revealed that GSH is involved in the synergistic multiple steps crosstalk
      through ET as well as SA to combat environmental stress. 

PMID- 24913052
TI  - Fructan metabolism and expression of genes coding fructan metabolic enzymes
      during cold acclimation and overwintering in timothy (Phleum pratense).
AB  - Metabolism of fructans in temperate grasses dynamically fluctuates before and
      during winter and is involved in the overwintering activity of plants. We
      monitored three candidate factors that may be involved in seasonal fructan
      metabolism in timothy (Phleum pratense): transcription levels of two
      fructosyltransferase (PpFT1 and PpFT2) genes and one fructan exohydrolase (Pp6
      FEH1) gene during fall and winter and under artificially cold conditions.
      Functional analysis using a recombinant enzyme for PpFT2, a novel
      fructosyltransferase cDNA, revealed that it encoded sucrose:fructan 6
      fructosyltransferase, with enzymatic properties different from previously
      characterized PpFT1. PpFT1 transcripts decreased from September to December as
      the amount of fructans increased, whereas PpFT2 transcripts increased in timothy
      crowns. PpFT2 was transcriptionally more induced than PpFT1 in response to cold
      and sucrose in timothy seedlings. A rapid increase in Pp6-FEH1 transcripts and
      increased monosaccharide content were observed in timothy crowns when air
      temperature was continuously below 0 degrees C and plants were not covered by
      snow. Transcriptional induction of Pp6-FEH1 by exposure to -3 degrees C was also
      observed in seedlings. These findings suggest Pp6-FEH1 involvement in the second
      phase of hardening. PpFT1 and PpFT2 transcription levels decreased under snow
      cover, whereas Pp6-FEH1 transcription levels were constant, which corresponded
      with the fluctuation of fructosyltransferase and fructan exohydrolase activities.
      Inoculation with snow mold fungi (Typhula ishikariensis) increased Pp6-FEH1
      transcription levels and accelerated hydrolysis of fructans. These results
      suggest that transcriptional regulation of genes coding fructan metabolizing
      enzymes is partially involved in the fluctuation of fructan metabolism during
      cold acclimation and overwintering. 

PMID- 24913053
TI  - The tomato phosphatidylinositol-phospholipase C2 (SlPLC2) is required for defense
      gene induction by the fungal elicitor xylanase.
AB  - The tomato [Solanum lycopersicum (Sl)] phosphatidylinositol-phospholipase C (PI
      PLC) gene family is composed of six members, named SlPLC1 to SlPLC6,
      differentially regulated upon pathogen attack. We have previously shown that the
      fungal elicitor xylanase rapidly induces nitric oxide (NO), which is required for
      PI-PLCs activity and downstream defense responses in tomato cell suspensions.
      Here, we show that all six SlPLC genes are expressed in tomato cell suspensions.
      Treatment of the cells with xylanase induces an early increase in SlPLC5
      transcript levels, followed by a raise of the amount of SlPLC2 transcripts. The
      production of NO is required to augment SlPLC5 transcript levels in xylanase
      treated tomato cells. Xylanase also induces SlPLC2 and SlPLC5 transcript levels
      in planta. We knocked-down the expression of SlPLC2 and SlPLC5 by virus-induced
      gene silencing. We found that SlPLC2 is required for xylanase-induced expression
      of the defense-related genes PR1 and HSR203J. 

PMID- 24913054
TI  - GA4 and IAA were involved in the morphogenesis and development of flowers in
      Agapanthus praecox ssp. orientalis.
AB  - The transition from vegetative to reproductive growth represents a major phase
      change in angiosperms. Hormones play important roles in this process. In this
      study, gibberellic acid (GA), cytokinins (CKs), indoleacetic acid (IAA), and
      abscisic acid (ABA) were analyzed during the flowering in Agapanthus praecox ssp.
      orientalis. Eleven types of endogenous gibberellins in addition to GA1 were
      detected in various organs. GA9 was detected with the highest concentrations,
      followed by GA5, GA8, and GA19. However, GA4 was the main bioactive GA that was
      involved in the regulation of flowering. Eight types of endogenous cytokinins
      were detected in A. praecox ssp. orientalis, and zeatin, zeatin riboside, zeatin
      O-glucoside, and N(6)-isopentenyladenosine-5-monophosphate were present at higher
      levels throughout the study, of which zeatin plays an important role in the
      development of various organs. IAA increased by 581% in the shoot tips from the
      vegetative to inflorescence bud stages and had the most significant changes
      during flowering. Phytohormone immunolocalization analysis suggested that IAA
      involved in differentiation and development of each floral organs, GA and zeatin
      play important roles in floret primordia differentiation and ovule development.
      Using exogenous plant growth regulators proved that GA signaling regulate the
      scape elongation and stimulate early-flowering, and IAA signaling is involved in
      the pedicel and corolla elongation and delay flowering slightly. 

PMID- 24913055
TI  - Immune thrombocytopenia in chronic myelomonocytic leukemia.
AB  - OBJECTIVE: Autoimmune disorders, including immune cytopenia, are encountered in
      the setting of chronic myelomonocytic leukemia (CMML). The aim of our study was
      to analyze the association of immune thrombocytopenia (ITP) with chronic
      myelomonocytic leukemia (CMML). METHODS: We carried out a retrospective cohort
      study on 565 patients with immune thrombocytopenia (ITP) followed in the French
      referral center for adult's immune cytopenia. A literature review using MEDLINE
      (National Library of Medicine, Bethesda, MD) was also performed. RESULTS: Eight
      patients (5 male, 76.3 + 9.8 yr old) with ITP-associated CMML were identified in
      our national cohort. Thirteen cases were reported in literature from 1984 to
      2013. Mean age was 65.3 +/- 18.5 yr. Sex ratio (M/F) was 1/0.6. ITP unveiled CMML
      in all but four cases (17/21; 80.9%). ITP occurred in the setting of low-grade
      CMML in all cases, with neither reported progression nor acute myeloid leukemia
      transformation during follow-up. Overall, karyotype analysis revealed cytogenetic
      abnormalities in six cases (6/16; 37.5%). ITP had a chronic course in most cases
      and shares, according to the low level of bleeding complications and the high
      response rate to treatment such as corticosteroids and splenectomy, the usual
      characteristics of primary ITP. CONCLUSION: Although the association of a well
      defined ITP and CMML is rare, our study suggests that CMML-associated ITP should
      be treated according to current guidelines for primary ITP.

PMID- 24913056
TI  - Nanotechnology and cancer nanomedicine.

PMID- 24913059
TI  - Coronary artery disease: Long-term superiority of CABG surgery for three-vessel
      disease confirmed.

PMID- 24913058
TI  - Cardiac imaging for assessment of left atrial appendage stasis and thrombosis.
AB  - Atrial fibrillation (AF) is the most-common arrhythmia in the elderly population
      (age >65 years). The left atrial appendage (LAA) is the main location of thrombus
      formation, predominantly in patients with nonvalvular AF. This Review is focused
      on the pathophysiology, assessment, and clinical implications of stasis (or
      spontaneous echocardiographic contrast; SEC) and thrombus formation in the LAA.
      The gold-standard modality for assessment of SEC and thrombus in the LAA is
      echocardiography, particularly transoesophageal echocardiography (TEE). Cardiac
      CT (CCT) is an accurate, noninvasive alternative to TEE for the detection of LAA
      thrombi, distinctly when delayed-imaging acquisition protocols are used.
      Prospective studies to validate the use of cardiac MRI (CMR) for this purpose are
      needed, and will avoid the need for radiation and iodinated contrast. CCT or CMR
      could potentially be implemented to rule out LAA thrombus, avoiding unnecessary
      preprocedural TEE. Cardiac imaging is also of primary importance in the setting
      of LAA closure devices and electrophysiological studies. New trials are needed to
      compare the various imaging modalities, with surgicopathological findings as a
      reference standard. 

PMID- 24913060
TI  - Interventional cardiology: COMFORTABLE biodegradable stents in a new CENTURY?

PMID- 24913057
TI  - Common mechanisms of DNA translocation motors in bacteria and viruses using one
      way revolution mechanism without rotation.
AB  - Biomotors were once described into two categories: linear motor and rotation
      motor. Recently, a third type of biomotor with revolution mechanism without
      rotation has been discovered. By analogy, rotation resembles the Earth rotating
      on its axis in a complete cycle every 24h, while revolution resembles the Earth
      revolving around the Sun one circle per 365 days (see animations
      http://nanobio.uky.edu/movie.html). The action of revolution that enables a motor
      free of coiling and torque has solved many puzzles and debates that have occurred
      throughout the history of viral DNA packaging motor studies. It also settles the
      discrepancies concerning the structure, stoichiometry, and functioning of DNA
      translocation motors. This review uses bacteriophages Phi29, HK97, SPP1, P22, T4,
      and T7 as well as bacterial DNA translocase FtsK and SpoIIIE or the large
      eukaryotic dsDNA viruses such as mimivirus and vaccinia virus as examples to
      elucidate the puzzles. These motors use ATPase, some of which have been confirmed
      to be a hexamer, to revolve around the dsDNA sequentially. ATP binding induces
      conformational change and possibly an entropy alteration in ATPase to a high
      affinity toward dsDNA; but ATP hydrolysis triggers another entropic and
      conformational change in ATPase to a low affinity for DNA, by which dsDNA is
      pushed toward an adjacent ATPase subunit. The rotation and revolution mechanisms
      can be distinguished by the size of channel: the channels of rotation motors are
      equal to or smaller than 2 nm, that is the size of dsDNA, whereas channels of
      revolution motors are larger than 3 nm. Rotation motors use parallel threads to
      operate with a right-handed channel, while revolution motors use a left-handed
      channel to drive the right-handed DNA in an anti-chiral arrangement. Coordination
      of several vector factors in the same direction makes viral DNA-packaging motors
      unusually powerful and effective. Revolution mechanism that avoids DNA coiling in
      translocating the lengthy genomic dsDNA helix could be advantageous for cell
      replication such as bacterial binary fission and cell mitosis without the need
      for topoisomerase or helicase to consume additional energy.

PMID- 24913062
TI  - Pharmacological chaperones increase residual beta-galactocerebrosidase activity
      in fibroblasts from Krabbe patients.
AB  - Krabbe disease or globoid cell leukodystrophy is a degenerative, lysosomal
      storage disease resulting from the deficiency of beta-galactocerebrosidase
      activity. This enzyme catalyzes the lysosomal hydrolysis of galactocerebroside
      and psychosine. Krabbe disease is inherited as an autosomal recessive trait, and
      many of the 70 disease-causing mutations identified in the GALC gene are
      associated with protein misfolding. Recent studies have shown that enzyme
      inhibitors can sometimes translocate misfolded polypeptides to their appropriate
      target organelle bypassing the normal cellular quality control machinery and
      resulting in enhanced activity. In search for pharmacological chaperones that
      could rescue the beta-galactocerebrosidase activity, we investigated the effect
      of alpha-Lobeline or 3',4',7-trihydroxyisoflavone on several patient-derived
      fibroblast cell lines carrying missense mutations, rather than on transduced cell
      lines. Incubation of these cell lines with alpha-lobeline or 3',4',7
      trihydroxyisoflavone leads to an increase of beta-galacocerebrosidase activity in
      p.G553R + p.G553R, in p.E130K + p.N295T and in p.G57S + p.G57S mutant forms over
      the critical threshold. The low but sustained expression of beta
      galactocerebrosidase induced by these compounds is a promising result; in fact,
      it is known that residual enzyme activity of only 15-20% is sufficient for
      clinical efficacy. The molecular interaction of the two chaperones with beta
      galactocerebrosidase is also supported by in silico analysis. Collectively, our
      combined in silico-in vitro approach indicate alpha-lobeline and 3',4',7
      trihydroxyisoflavone as two potential pharmacological chaperones for the
      treatment or improvement of quality of life in selected Krabbe disease patients.

PMID- 24913063
TI  - Methionine-induced hyperhomocysteinemia and bleomycin hydrolase deficiency alter
      the expression of mouse kidney proteins involved in renal disease.
AB  - SCOPE: Hyperhomocysteinemia (HHcy) induced by dietary or genetic factors is
      linked to kidney disease. Bleomycin hydrolase (Blmh) metabolizes Hcy-thiolactone
      to Hcy. We aimed to explain the role of dietary HHcy in kidney disease. METHODS
      AND RESULTS: We examined kidney proteome in dietary HHcy and Blmh-knockout mouse
      models using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass spectrometry.
      We found that the kidney proteome was altered by dietary HHcy and the Blmh(-/-)
      genotype. Proteins involved in metabolism of lipoprotein (ApoA1), amino acid and
      protein (Acy1, Hspd1), carbohydrate (Pdhb, Fbp1-isoform 1, Eno1), and energy
      metabolism (Ndufs8, Ldhd) were down-regulated. Proteins involved in carbohydrate
      metabolism (Fbp1-isoform 2), oxidative stress response (Prdx2), and
      detoxification (Glod4) were up-regulated. The Blmh(-/-) genotype down-regulated
      Glod4 isoform 3 mRNA but did not affect isoform 1 mRNA expression in mouse
      kidneys, suggesting post-transcriptional regulation of the Glod4 protein by the
      Blmh(+/+) genotype. Responses of ApoA1, Acy1, Hspd1, Ndufs8, Fbp1, Eno1, and
      Prdx2 to HHcy and/or Blmh deficiency mimic their responses to renal disease.
      CONCLUSION: Our findings indicate that Blmh interacts with diverse cellular
      processes--lipoprotein, amino acid and protein, carbohydrate, and energy
      metabolisms, detoxification, antioxidant defenses--that are essential for normal
      kidney homeostasis and that deregulation of these processes can account for the
      involvement of HHcy in kidney disease.

PMID- 24913064
TI  - Severe congenital cutis laxa with cardiovascular manifestations due to homozygous
      deletions in ALDH18A1.
AB  - Autosomal recessive cutis laxa (ARCL) type 2 constitutes a heterogeneous group of
      diseases mainly characterized by lax and wrinkled skin, skeletal anomalies, and a
      variable degree of intellectual disability. ALDH18A1-related ARCL is the most
      severe form within this disease spectrum. Here we report on the clinical and
      molecular findings of two affected individuals from two unrelated families. The
      patients presented with typical features of de Barsy syndrome and an overall
      progeroid appearance. However, the phenotype was highly variable including
      cardiovascular involvement in the more severe case. Investigation of a skin
      biopsy of one patient revealed not only the typical alterations of elastic
      fibers, but also an altered structure of mitochondria in cutaneous fibroblasts.
      Using conventional sequencing and copy number analysis we identified a frameshift
      deletion of one nucleotide and a microdeletion affecting the ALDH18A1 gene,
      respectively, in a homozygous state in both patients. Expression analysis in
      dermal fibroblasts from the patient carrying the microdeletion showed an almost
      complete absence of the ALDH18A1 mRNA resulting in an absence of the ALDH18A1
      protein. So far, only 13 affected individuals from seven unrelated families
      suffering from ALDH18A1-related cutis laxa have been described in literature. Our
      findings provide new insights into the clinical spectrum and show that beside
      point mutations microdeletions are a possible cause of ALDH18A1-ARCL. 

PMID- 24913065
TI  - GAVI aims to double its child vaccination rate between 2016 and 2020.

PMID- 24913061
TI  - PET imaging of inflammation in atherosclerosis.
AB  - PET imaging of atherosclerosis can quantify several in vivo pathological
      processes occurring within the arterial system. (18)F-fluorodeoxyglucose (FDG) is
      the most-commonly used PET tracer, with well-established roles in atherosclerosis
      imaging. In this context, the (18)F-FDG signal largely reflects tracer uptake by
      plaque macrophages and, therefore, inflammation with smaller contributions from
      other resident cell types. As a marker of plaque vulnerability, the (18)F-FDG PET
      signal can be used to help to identify patients at the highest risk of clinical
      events. (18)F-FDG PET has also been used successfully as a surrogate end point in
      clinical trials of antiatherosclerotic therapies. Nonetheless, imaging
      atherosclerosis with (18)F-FDG has several limitations. Most importantly,
      coronary artery imaging is problematic because (18)F-FDG accumulates in all cells
      that metabolize glucose, and background myocardial uptake is generally greater
      than any signal originating from a plaque. To help to overcome these limitations,
      several novel PET tracers, which might be more-specifically targeted than (18)F
      FDG, have been tested in atherosclerosis imaging. These tracers are designed to
      track inflammation, hypoxia, neoangiogenesis, or active calcification, which are
      all precursors to plaque rupture and its clinical sequelae. 

PMID- 24913067
TI  - Time-varying sliding-coefficient-based decoupled terminal sliding-mode control
      for a class of fourth-order systems.
AB  - A time-varying sliding-coefficient-based decoupled terminal sliding mode control
      strategy is presented for a class of fourth-order systems. First, the fourth
      order system is decoupled into two second-order subsystems. The sliding surface
      of each subsystem was designed by utilizing time-varying coefficients. Then, the
      control target of one subsystem to another subsystem was embedded. Thereafter, a
      terminal sliding mode control method was utilized to make both subsystems
      converge to their equilibrium points in finite time. The simulation results on
      the inverted pendulum system demonstrate that the proposed method exhibits a
      considerable improvement in terms of a faster dynamic response and lower IAE and
      ITAE values as compared with the existing decoupled control methods. 

PMID- 24913068
TI  - Metacognitive-like information seeking in lion-tailed macaques: a generalized
      search response after all?
AB  - Previous research has demonstrated that Old World primates (both apes and
      monkeys) seek information about the location of a hidden food item, unless they
      are privy to the hiding process. This has been cited as evidence of
      metacognition. However, these results could also be interpreted using non
      metacognitive accounts, including a generalized search response to uncertainty,
      in which subjects reach for food when it is seen, or search for food until it is
      spotted. In the present research, lion-tailed macaques were tested on an object
      choice task. Conditions varied with respect to the visibility of the baiting
      process, and whether the location of the hidden food could be inferred by logical
      exclusion. Additionally, the hidden food could be located visually before a
      choice was made, by peering under the objects through a Plexiglas tray. Across
      conditions, monkeys consistently looked for the food when it had not been seen,
      even if its location could be inferred, despite the fact that these monkeys are
      capable of inference by exclusion. This suggests that apparently 'metacognitive'
      information seeking in monkeys may instead reflect a generalized search strategy.
      Alternatively, it is possible that monkeys only have metacognitive access to
      certain types of knowledge, including that obtained visually. Results are
      discussed with respect to the likelihood of metacognition in this species and the
      evolutionary emergence of metacognition across species. 

PMID- 24913066
TI  - Vandetanib and indwelling pleural catheter for non-small-cell lung cancer with
      recurrent malignant pleural effusion.
AB  - INTRODUCTION/BACKGROUND: Non-small-cell lung cancer patients with malignant
      pleural effusion have a poor overall median survival (4.3 months). VEGF is a key
      regulator of pleural effusion production. It is unknown if pharmacological
      inhibition of VEGF signaling modifies the disease course of non-small-cell lung
      cancer patients with recurrent malignant pleural effusion. We report the final
      results of a single-arm phase II clinical trial of the VEGF receptor inhibitor,
      vandetanib, combined with intrapleural catheter placement in patients with non
      small-cell lung cancer and recurrent malignant pleural effusion, to determine
      whether vandetanib reduces time to pleurodesis. PATIENTS AND METHODS: Non-small
      cell lung cancer patients with proven metastatic disease to the pleural space
      using pleural fluid cytology or pleural biopsy who required intrapleural catheter
      placement were eligible for enrollment. On the same day of the intrapleural
      catheter insertion, the patients were started on a daily oral dose of 300 mg
      vandetanib, for a maximum of 10 weeks. The primary end point was time to
      pleurodesis, with response rate as the secondary end point. Exploratory analyses
      included measurement of pleural fluid cytokines and angiogenic factors before and
      during therapy. RESULTS: Twenty eligible patients were included in the trial.
      Eleven patients completed 10 weeks of treatment. Median time to pleurodesis was
      35 days (95% confidence interval, 15-not applicable). Median time to pleurodesis
      in the historical cohort was 63 days (95% confidence interval, 45-86) when
      adjusted for Eastern Cooperative Oncology Group performance status <= 2.
      CONCLUSION: Vandetanib therapy was well tolerated; however, it did not
      significantly reduce time to pleurodesis.

PMID- 24913069
TI  - High prevalence of Cfr-producing Staphylococcus species in retail meat in
      Guangzhou, China.
AB  - BACKGROUND: The emergence and wide distribution of the transferable gene for
      linezolid resistance, cfr, in staphylococci of human and animal origins is of
      great concern as it poses a serious threat to the public health. In the present
      study, we investigated the emergence and presence of the multiresistance gene,
      cfr, in retail meat sourced from supermarkets and free markets of Guangzhou,
      China. RESULTS: A total of 118 pork and chicken samples, collected from Guangzhou
      markets, were screened by PCR for cfr. Twenty-two Staphylococcus isolates
      obtained from 12 pork and 10 chicken samples harbored cfr. The 22 cfr-positive
      staphylococci isolates, including Staphylococcus equorum (n = 8), Staphylococcus
      simulans (n = 7), Staphylococcus cohnii (n = 4), and Staphylococcus sciuri (n =
      3), exhibited 17 major SmaI pulsed-field gel electrophoresis (PFGE) patterns. In
      14 isolates, cfr was located on the plasmids. Sequence analysis revealed that the
      genetic structures (including DeltatnpA of Tn558, IS21-558, DeltatnpB, and tnpC
      of Tn558, orf138, fexA) of cfr in plasmid pHNTLD18 of a S. sciuri strain and in
      the plasmid pHNLKJC2 (including rep, Deltapre/mob, cfr, pre/mob and partial ermC)
      of a S. equorum strain were identical or similar to the corresponding regions of
      some plasmids in staphylococcal species of animal and human origins. CONCLUSIONS:
      To the best of our knowledge, this is the first study to report the presence of
      the multiresistance gene, cfr, in animal meat. A high occurrence of cfr was
      observed in the tested retail meat samples. Thus, it is important to monitor the
      presence of cfr in animal foods in China.

PMID- 24913070
TI  - Dexmedetomidine: a review of applications for cardiac surgery during
      perioperative period.
AB  - Cardiac surgery is associated with a high incidence of cardiovascular and other
      complications during the perioperative period that translate into increased
      mortality and prolonged hospital stays. Safe comprehensive perioperative
      management is required to eliminate these adverse events. Dexmedetomidine is a
      selective alpha2-adrenoreceptor agonist that has been described as an ideal
      medication in the perioperative period of cardiac surgery. The major clinical
      effects of dexmedetomidine in this perioperative period can be summarized as
      attenuating the hemodynamic response, cardioprotective effects, antiarrhythmic
      effects, sedation in the ICU setting, treatment of delirium, and procedural
      sedation. Although there are some side effects of dexmedetomidine, it is emerging
      as an effective therapeutic agent in the management of a wide range of clinical
      conditions with an efficacious, safe profile. The present review serves as an
      overview update in the diverse applications of dexmedetomidine for cardiac
      surgery during the perioperative period. 

PMID- 24913073
TI  - Chronic ulcerated lesion of the nasal vestibule. Primary nasal leishmaniasis.

PMID- 24913072
TI  - Early contamination of European flounder (Platichthys flesus) by PCDD/Fs and
      dioxin-like PCBs in European waters.
AB  - Contamination levels and profiles of 7 polychlorinated-p-dioxins, 10
      polychlorinated furans (PCDD/Fs) and 12 dioxin-like polychlorinated biphenyls (dl
      PCBs) were investigated in juvenile European flounder (Platichthys flesus)
      captured in different nursery areas in the northeastern Atlantic coast across its
      geographical distribution range. The toxic equivalent concentrations (WHO
      TEQfish) were also determined in order to evaluate which P. flesus population was
      more exposed to dioxin-like toxicity. Juveniles caught in the Sorfjord (Norway)
      showed the lowest WHO-TEQfish concentration (0.052 pg WHO-TEQfish g(-1)wet
      weight) whereas the highest value was observed in fish from the Wadden Sea (The
      Netherlands; 0.291 pg WHO-TEQfish g(-1)ww), mainly due to the greater
      contribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin, the most toxic congener.
      Nonetheless, when comparing the results with existent tissue residue-based
      toxicity benchmarks, no adverse effects resulting from PCDD/Fs and dl-PCBs are
      expected to occur in flounder from the studied systems.

PMID- 24913071
TI  - Assessment of pollution in the Bizerte lagoon (Tunisia) by the combined use of
      chemical and biochemical markers in mussels, Mytilus galloprovincialis.
AB  - In order to assess the environmental quality of the Bizerte lagoon (Tunisia),
      biomarker and contaminant levels were measured in Mediterranean mussels (Mytilus
      galloprovincialis) from five selected sites. Persistent organic pollutants (POPs)
      were quantified in whole body and enzyme activities such as acetylcholinesterase
      (AChE), catalase (CAT) and glutathione S-transferase (GST) in gills. Despite the
      relatively low levels of organic contaminants, the selected biomarkers responded
      differently according to the pollution level at the different sites. GST and AChE
      activities were correlated with the amount of DDTs in mussel tissues. These two
      enzymatic activities were also correlated to temperature and pH. No significant
      difference was observed for CAT activity. Principal component analysis showed a
      clear separation of sampling sites in three different assemblages which is
      consistent with POP body burden in mussels. Our results confirmed the usefulness
      of combining biomarker and chemical analyses in mussels to assess chemical
      pollution in the Bizerte lagoon. 

PMID- 24913074
TI  - Post liver transplant presentation of needle-track metastasis of hepatocellular
      carcinoma following percutaneous liver biopsy.
AB  - Hepatocellular carcinoma (HCC) is one of the few malignant tumours often treated
      without prior histological confirmation (in the patient with cirrhosis). Contrast
      enhanced cross-sectional imaging is frequently diagnostic of HCC with a high
      degree of accuracy. However, on occasion, a liver biopsy is required, a
      complication of which can be needle-track metastasis. We present the case of a 57
      year-old man who had previously undergone a liver transplant; he was found to
      have abdominal wall metastasis at the site of a prior percutaneous biopsy. This
      is the second case until now date of needle-track metastasis that presented
      following liver transplantation. 

PMID- 24913075
TI  - Supplemental tooth in primary dentition.
AB  - An extra tooth causing numerical excess in dentition is described as
      supernumerary tooth, and the resultant condition is termed as hyperdontia.
      Hyperdontia is more commonly seen in the permanent dentition than primary one.
      Supernumerary tooth which resembles tooth shape and supplements for occlusion is
      called as supplemental tooth. We present a case with supplemental tooth in
      primary dentition. 

PMID- 24913076
TI  - Aggressive dentigerous cyst with ectopic central incisor.
AB  - Dentigerous cysts form from accumulation of fluid between reduced enamel
      epithelium and the crown of an unerupted tooth. They cause several difficulties
      such as swelling, non-eruption of the involved teeth, and displacement of
      adjacent teeth, and thus require early detection and prompt treatment. Treatment
      ranges from marsupialisation to enucleation. Enucleation is rarely used in
      children compared with marsupialisation. This paper discusses successful use of
      enucleation for treating a dentigerous cyst and explains the need for such a
      radical procedure.

PMID- 24913077
TI  - Pyogenic hepatic abscess presenting years after a choledochojejunostomy: a rare
      clinical occurrence.
AB  - A 69-year-old Caucasian man presented with fever, chills/rigors and night sweats
      since 6 days. Blood cultures (4/4) initially reported Gram negative lactose
      fermenting rods. Physical examination was fairly benign which included a normal
      abdominal examination. Laboratory tests were significant for an elevated white
      cell count, erythrocyte sedimentation rate and C reactive protein . Empirically,
      he was treated with piperacillin tazobactam. A chart review showed that he had
      undergone a choledochojejunostomy for a pancreatic head tumour 7 years before. We
      found a few reported cases of hepatic abscesses after choledochojejunostomy
      presenting years after the procedure. An abdominal CT scan confirmed our
      suspicion. Percutaneous drainage was performed and his antibiotics were switched
      to ciprofloxacin and metronidazole, based on the sensitivity report. The
      patient's clinical condition steadily improved.

PMID- 24913078
TI  - Thrombosed aneurysm as the initial manifestation of Takayasu arteritis.
AB  - Takayasu arteritis (TA) is a large-vessel vasculitis characterised by stenosis,
      dilation and/or aneurysm formation. We present a case of a 43-year-old man with
      an initial manifestation of an acute thrombosed aneurysm. He was found to have a
      thrombosed right common femoral artery aneurysm on Doppler ultrasound. Physical
      examinations revealed a substantial difference in blood pressure level between
      bilateral upper extremities, and absent pulses at right upper and lower
      extremities. The diagnosis was confirmed by angiography, which revealed 100%
      occlusion of the right common femoral artery. Biopsy of the thrombosed aneurysm
      was consistent with a diffuse lymphocytic subendothelial infiltrate. The patient
      was treated with high-dose corticosteroids and had a good response to treatment,
      as demonstrated by a decrease in sedimentation rate, and recovery of the right
      side pulses. This case helps to create awareness among physicians that TA may
      present with an acute occlusion of an aneurysm without the typical warning
      symptoms of TA. 

PMID- 24913079
TI  - Cyclopia syndrome.

PMID- 24913080
TI  - Splenic abscess due to acute pyelonephritis.

PMID- 24913081
TI  - Acute coronary syndrome.
AB  - The paramedics brought a 60-year-old man to the emergency department after a
      sudden onset of shortness of breath with a subsequent drop in the Glasgow Coma
      Scale (GCS). On arrival the patient looked peri-arrest. His O2 saturations were
      84% on 15 L of oxygen. He had gasping breathing with a completely silent chest
      and the GCS was 6/15 (E=1, V=1, M=4). The blood gas revealed type-2 respiratory
      failure. The chest X-ray was unremarkable and ECG was not indicative for cardiac
      catheterisation lab activation. Bedside shock scan was done which showed global
      hypokinesia of the left ventricle. In spite of unconvincing ECG and chest X-ray,
      an acute cardiac event was diagnosed in view of an abnormal bedside echo. The
      patient was transferred to the cardiac catheterisation lab for urgent
      percutaneous coronary intervention which revealed critical stenosis of the left
      main stem coronary artery, which was successfully stented. The patient had a good
      recovery from the life-threatening event.

PMID- 24913082
TI  - The naughty knot in catheterisation laboratory.

PMID- 24913083
TI  - Gregg syndrome aka embryopathia rubeolaris: CT illustration.

PMID- 24913084
TI  - Undigested food on awakening with persistent halitosis.

PMID- 24913085
TI  - Bone metastases and hypercalcaemia from cutaneous squamous cell carcinoma.

PMID- 24913086
TI  - Acute renal failure and type B lactic acidosis as first manifestation of
      extranodal T-cell lymphoblastic lymphoma.
AB  - We describe a rare case of a 19-year-old male patient with a history of epilepsy
      and developmental delay who presented with acute renal failure (ARF) and lactic
      acidosis (LA) as the first manifestation of T-cell lymphoblastic lymphoma. Renal
      ultrasound and CT of the abdomen showed renal parenchymal infiltration, and renal
      biopsy demonstrated T-cell lymphoblastic lymphoma. LA, ARF and electrolyte
      abnormalities were refractory to the initial treatment of bicarbonate infusion
      and hydration. However, these abnormalities rapidly normalised after the
      initiation of chemotherapy, suggesting that the LA and ARF were secondary to
      lymphomatous renal infiltration. 

PMID- 24913087
TI  - The risk of venous thromboembolism in renal cell carcinoma patients with residual
      tumor thrombus: reply.

PMID- 24913088
TI  - Is the omega-3 index a valid marker of intestinal membrane phospholipid EPA+DHA
      content?
AB  - Despite numerous studies investigating n-3 long chain polyunsaturated fatty acid
      (LCPUFA) supplementation and inflammatory bowel diseases (IBD), the extent to
      which dietary n-3 LCPUFAs incorporate in gastrointestinal (GI) tissues and
      correlate with red blood cell (RBC) n-3 LCPUFA content is unknown. In this study,
      mice were fed three diets with increasing percent of energy (%en) derived from
      eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA). Dietary levels reflected
      recommended intakes of fish/fish oil by the American Heart Association. We
      analyzed the FA composition of phospholipids extracted from RBCs, plasma, and GI
      tissues. We observed that the 0.1%en EPA+DHA diet was sufficient to significantly
      increase the omega-3 index (RBC EPA+DHA) after 5 week feeding. The baseline EPA
      levels were 0.2-0.6% across all tissues increasing to 1.6-4.3% in the highest
      EPA+DHA diet; these changes resulted in absolute increases of 1.4-3.9% EPA across
      tissues. The baseline DHA levels were 2.2-5.9% across all tissues increasing to
      5.8-10.5% in the highest EPA+DHA diet; these changes resulted in absolute
      increases of 3.2-5.7% DHA across tissues. These increases in EPA and DHA across
      all tissues resulted in strong (r>0.91) and significant (P<0.001) linear
      correlations between the omega-3 index and plasma/GI tissue EPA+DHA content,
      suggesting that the omega-3 index reflects the relative amounts of EPA+DHA in GI
      tissues. These data demonstrate that the GI tissues are highly responsive to
      dietary LCPUFA supplementation and that the omega-3 index can serve as a valid
      biomarker for assessing dietary EPA+DHA incorporation into GI tissues. 

PMID- 24913089
TI  - Obese children experience higher plantar pressure and lower foot sensitivity than
      non-obese.
AB  - BACKGROUND: Children obesity is a risk factor for several dysfunctions and
      diseases, with negative effects on the morphology of the locomotor system,
      plantar pressure and body stability. A relationship between postural control and
      sensorimotor information has been assumed. However, there is few data on the
      effects of children obesity on the availability of sensorial information from the
      foot during standing. METHODS: Twenty obese and twenty non-obese children were
      evaluated for foot sensitivity and plantar pressure during unipedal and bipedal
      stance. Data were compared between obese and non-obese participants, between foot
      regions and between legs. FINDINGS: Obese children experiences higher plantar
      pressure and have lower foot sensitivity than non-obese. Additionally, obese
      children had similar sensitivity for different foot regions, as compared to the
      non-obese. INTERPRETATION: Children obesity negatively influences foot
      sensitivity. Bipedal stance seemed more sensitive to differentiate between obese
      and non-obese. Higher plantar pressure and lower foot sensitivity in obese
      children may affect performance of weight bearing activities, contribute to
      higher risk of foot injuries and have potential implication for children footwear
      design and clinical physical examination.

PMID- 24913090
TI  - Health related quality of life (HRQoL) after cystectomy: comparison between
      orthotopic neobladder and ileal conduit diversion.
AB  - INTRODUCTION: Radical cystectomy and urinary diversion carries a high morbidity.
      Quality of life and body image are important considerations for urinary diversion
      (UD). We wanted to conduct a systematic review of literature to see which form UD
      offers a better quality of life (QoL). METHODS: We searched MEDLINE, Pubmed,
      EMBASE, CINAHL and the Cochrane library for studies using the following key
      words: 'quality of life' and 'ileal conduit', 'orthotopic neobladder', 'continent
      diversion' and 'urinary diversion'. All English language articles on UD surgery
      were included in the original search from 1990 to 2014. To improve the quality of
      evidence, we stratified our inclusion criteria into studies that report on QoL in
      both forms of UD using at least one validated questionnaire. RESULTS: Twenty-one
      studies (2285 patients) were included in our study all of which used at least one
      validated tool. The most frequently used tools were the SF-36, EORTC QLQ-C30 and
      FACT BL (10, 8, 5 studies respectively). None of the studies were randomised and
      only 4 studies were prospectively designed. Sixteen studies reported no
      difference in QoL between the two types of urinary diversion and four studies
      reported a better QoL with orthotopic neobladder of which 2 studies had younger
      and fitter patients. On the other hand, one study reported a better QoL in ileal
      conduit patients. CONCLUSION: Orthotopic neobladder urinary diversion shows a
      marginally better quality of life scores compared to ileal conduit diversion
      especially when considering younger and fitter patients.

PMID- 24913091
TI  - Prophylactic thoracic duct ligation has unfavorable impact on overall survival in
      patients with resectable oesophageal cancer.
AB  - PURPOSE: This study aimed to determine the impact of prophylactic thoracic duct
      ligation on overall survival in resectable oesophageal cancer patients. METHODS:
      We conducted a retrospective analysis of 1804 patients with oesophageal cancers
      who underwent complete resection between December 1996 and December 2008. Based
      on the management of the thoracic duct during surgery, patients were classified
      into the following two groups: no prophylactic thoracic duct ligation group
      (NPLG, n = 815) and prophylactic thoracic duct ligation group (PLG, n = 989). Log
      rank test was used to assess the survival differences between groups. Subgroup
      analysis and the Cox proportional hazards model were used to further determine
      the impact of thoracic duct ligation on overall survival. RESULTS: The occurrence
      rate of postoperative chylothorax was comparable between NPLG and PLG (0.9% vs.
      1.0%, p = 0.739). The median survival times for patients in the NPLG and PLG were
      54.4 months (95% interval confidence, CI: 46.9-61.9) and 42.9 months (95% CI:
      36.1-49.7), respectively (p = 0.002). The 2-year, 3-year, 5-year, and 10-year
      survival rates were 75.1%, 64.1%, 46.1%, and 35.1%, respectively, in the NPLG and
      65.3%, 54.7%, 43.3%, and 30.9%, respectively, in the PLG, with a statistically
      significant difference between the groups (p = 0.002). Multivariate Cox
      regression analysis and subgroup analyses also demonstrated that thoracic duct
      ligation during oesophagectomy unfavorably impacted the overall survival of
      oesophageal cancer patients. CONCLUSIONS: Prophylactic thoracic ligation reduces
      the overall survival, but doesn't reduce the occurrence of chylothorax of
      resectable oesophageal cancer patients. We suggest more data from other
      institutions to validate our results.

PMID- 24913092
TI  - Tissue inhibitor of matrix metalloproteinase-1 polymorphism, plasma TIMP-1
      levels, and antihypertensive therapy responsiveness in hypertensive disorders of
      pregnancy.
AB  - Tissue inhibitor of metalloproteinase (TIMP)-1 is a major endogenous inhibitor of
      matrix metalloproteinase (MMP)-9, which may affect the responsiveness to therapy
      in hypertensive disorders of pregnancy. We examined whether TIMP-1 polymorphism
      (g.-9830T>G, rs2070584) modifies plasma MMP-9 and TIMP-1 levels and the response
      to antihypertensive therapy in 596 pregnant: 206 patients with preeclampsia (PE),
      183 patients with gestational hypertension (GH) and 207 healthy pregnant
      controls. We also studied the TIMP-3 polymorphism (g.-1296T>C, rs9619311). Plasma
      MMP-9 and TIMP-1 levels were measured by ELISA. GH patients with the GG genotype
      for the TIMP-1 polymorphism had lower MMP-9 levels and MMP-9/TIMP-1 ratios than
      those with the TT genotype. PE patients with the TG genotype had higher TIMP-1
      levels. The G allele and the GG genotype were associated with PE and
      responsiveness to antihypertensive therapy in PE, but not in GH. Our results
      suggest that the TIMP-1 g.-9830T>G polymorphism not only promotes PE but also
      decreases the responses to antihypertensive therapy. 

PMID- 24913094
TI  - Abdominal aortic and iliac artery compression following penetrating trauma: a
      study of feasibility.
AB  - INTRODUCTION: Penetrating junctional trauma is a leading cause of preventable
      death on the battlefield. Similarly challenging in civilian settings,
      exsanguination from the vessels of the abdomen, pelvis, and groin can occur in
      moments. Therefore, iliac artery or abdominal aortic compression has been
      recommended. Based on prior research, 120 lbs (54 kg) or 140 lbs (63 kg) of
      compression may be required to occlude these vessels, respectively. Whether most
      rescuers can generate this amount of compression is unknown. OBJECTIVE: To
      determine how many people in a convenience sample of 44 health care professionals
      can compress 120 lbs and 140 lbs. METHODS: This study simulated aortic and iliac
      artery compression. Consent was obtained from 44 clinicians (27 female; 17 male)
      from two large urban hospitals in Edmonton, Alberta, Canada. Participants
      compressed the abdominal model, which consisted of a medical scale and a 250 ml
      bag of saline, covered by a folded hospital blanket and placed on the ground. In
      random order, participants compressed a force they believed maintainable for 20
      minutes ("maintainable effort") and then a maximum force they could maintain for
      two minutes ("maximum effort"). Compression was also performed with a knee.
      Descriptive statistics were used to evaluate the data. RESULTS: Compression was
      directly proportional to the clinician's body weight. Participants compressed a
      mean of 55% of their body weight with two hands at a maintainable effort, and 69%
      at a maximum effort. At maintainable manual effort, participants compressed a
      mean of 86 lbs (39 kg). Sixteen percent could compress over 120 lbs, but none
      over 140 lbs. At maximum effort, participants compressed a mean of 108 lbs (48
      kg). Thirty-four percent could compress greater than 120 lbs and 11% could
      compress greater than 140 lbs. Using a single knee, participants compressed a
      mean weight of 80% of their body weight with no difference between maintainable
      and maximum effort. CONCLUSION: This work suggests that bimanual compression
      following penetrating junctional trauma is feasible. However, it is difficult,
      and is not likely achievable or sustainable by a majority of rescuers. Manual
      compression (used to temporize until device application and operative rescue)
      requires a large body mass. To maintain 140 lbs of compression (for example
      during a lengthy transport), participants needed to weigh 255 lbs (115 kg).
      Alternatively, they needed to weigh 203 lbs (92 kg) to be successful during brief
      periods. Knee compression may be preferable, especially for lower-weight
      rescuers.

PMID- 24913095
TI  - Euclidean sections of protein conformation space and their implications in
      dimensionality reduction.
AB  - Dimensionality reduction is widely used in searching for the intrinsic reaction
      coordinates for protein conformational changes. We find the dimensionality
      reduction methods using the pairwise root-mean-square deviation (RMSD) as the
      local distance metric face a challenge. We use Isomap as an example to illustrate
      the problem. We believe that there is an implied assumption for the
      dimensionality-reduction approaches that aim to preserve the geometric relations
      between the objects: both the original space and the reduced space have the same
      kind of geometry, such as Euclidean geometry vs. Euclidean geometry or spherical
      geometry vs. spherical geometry. When the protein free energy landscape is mapped
      onto a 2D plane or 3D space, the reduced space is Euclidean, thus the original
      space should also be Euclidean. For a protein with N atoms, its conformation
      space is a subset of the 3N-dimensional Euclidean space R(3N). We formally define
      the protein conformation space as the quotient space of R(3N) by the equivalence
      relation of rigid motions. Whether the quotient space is Euclidean or not depends
      on how it is parameterized. When the pairwise RMSD is employed as the local
      distance metric, implicit representations are used for the protein conformation
      space, leading to no direct correspondence to a Euclidean set. We have
      demonstrated that an explicit Euclidean-based representation of protein
      conformation space and the local distance metric associated to it improve the
      quality of dimensionality reduction in the tetra-peptide and beta-hairpin
      systems.

PMID- 24913096
TI  - Sensitive and portable detection of telomerase activity in HeLa cells using the
      personal glucose meter.
AB  - Using the personal glucose meter, a portable sensor was fabricated to assay
      telomerase activity and study the telomerase inhibitor AZT. Hence, it provided a
      promising approach for the detection of enzyme activity and diagnosis of cancer. 

PMID- 24913097
TI  - Can medical students recognize depression? A survey at the Zagreb School of
      Medicine.
AB  - OBJECTIVE: The objective of this study was to investigate medical students'
      knowledge and attitudes towards depression. METHODS: Students attending their
      final year at Zagreb School of Medicine completed a set of standardized
      questionnaires, including attitudes towards psychiatric medication, attitudes
      towards depression, and personality inventory. RESULTS: In total, 199 students
      completed the questionnaire (response rate 77 %). Most medical students were only
      partially able to correctly identify major symptoms of depression, but did
      suggest referral to mental health specialists as the most appropriate course of
      action. They recognized social and biological causes of depression. Degree of
      correct identification of symptoms of depression correlated positively with non
      stigmatizing attitudes towards depression and negatively with stigmatizing
      attitudes towards depression. CONCLUSION: Students' attitudes toward depression
      may influence their recognition of symptoms of depression. Incorporation of these
      findings in development of undergraduate medical curricula may improve students'
      recognition of depression.

PMID- 24913098
TI  - Medical student psychiatric educators' perceptions of supports, resources, and
      rewards.
AB  - OBJECTIVE: The primary purpose of this study was to determine the adequacy of
      resources for medical student education in psychiatry in US medical schools.
      METHODS: An e-questionnaire was deployed to psychiatric educators in the
      Association of the Directors of Medical Student Education in Psychiatry (ADMSEP)
      regarding resources for fulfilling their educational mission. RESULTS: Medical
      student educators in psychiatry were neutral as to whether they had adequate
      mentoring, yet did report support from their chair. Participants' roles in
      medical student education and membership in ADMSEP enhanced their work
      satisfaction, career satisfaction, and career development. Many participants
      reflected a lack of adequate resources to achieve student education goals.
      CONCLUSIONS: There are opportunities for improvement in provision of teaching
      resources, mentoring for medical student educators, greater protected time for
      teaching and administration, and rewards (salary and non-monetary) for educators.
      If actualized, these improvements would promote optimization of medical student
      education in psychiatry.

PMID- 24913099
TI  - Engaging medical students in research: reaching out to the next generation of
      physician-scientists.
AB  - OBJECTIVE: The authors describe a multifaceted educational training approach
      aimed at increasing medical student involvement in psychiatric research. METHOD:
      A description of the initiative is provided, including the rationale and expected
      impact of each component. RESULTS: Medical student involvement in research
      projects has increased steadily since implementation. This applies to summer
      research projects as well as elective research rotations for senior medical
      students. Furthermore, a substantial proportion of students who participate in
      research continue to engage in research activities following completion of the
      program (e.g., through additional research participation, conference
      presentations). CONCLUSION: A proactive and well-organized approach to
      encouraging medical student participation in research can increase the number of
      students who choose to engage in a research and may ultimately help increase the
      number of physician-scientists.

PMID- 24913100
TI  - Zinc and propolis reduces cytotoxicity and proliferation in skin fibroblast cell
      culture: total polyphenol content and antioxidant capacity of propolis.
AB  - It has been demonstrated that zinc exerts its beneficial influence on skin
      fibroblasts. Propolis, a complex mixture of plant-derived and bees' products, was
      reported to stimulate cicatrization processes in skin and prevent infections. The
      aim of this study was to find out how zinc and propolis influence human skin
      fibroblasts in cell culture and to compare the effect of individual compounds to
      the effect of a mixture of zinc and propolis. In this study, zinc, as zinc
      aspartate, at a concentration of 16 MUM, increased human fibroblasts
      proliferation in cell culture, whereas propolis at a concentration of 0.01% (w/v)
      revealed antiproliferative and cytotoxic action followed by mild cell necrosis.
      In culture, zinc was effectively transported into fibroblasts, and propolis
      inhibited the amount of zinc incorporated into the cells. An addition of propolis
      to the medium caused a decrease in the Zn(II) amount incorporated into
      fibroblasts. The obtained results also indicate an appreciable antioxidant
      property of propolis and revealed its potential as a supplement when applied at
      doses lower than 0.01% (w/v). In conclusion, the present study showed that zinc
      had a protective effect on human cultured fibroblasts' viability, although
      propolis revealed its antiproliferative action and caused mild necrosis.

PMID- 24913101
TI  - A mineral and antioxidant-rich extract from the red marine Algae Alsidium
      corallinum exhibits cytoprotective effects against potassium bromate-induced
      erythrocyte oxidative damages in mice.
AB  - The present study was carried out to investigate potassium bromate toxicity in
      mice and the corrective effects of marine algae Alsidium corallinum. The red
      algae demonstrated its rich composition in phenols, triterpenes, flavonoids,
      alkaloids, tropolones, sodium, potassium, calcium, magnesium, iron, copper, and
      zinc. To confirm its antioxidant potential, an in vivo study was performed on
      adult mice. The animals were divided into four groups: group I were used as
      controls, group II received potassium bromate (0.5 g/L) via drinking water, group
      III received potassium bromate (0.5 g/L) by the same route as group II and 7% of
      A. corallinum ethanolic extract via their diet, and group IV received only 7% of
      algae. The potassium bromate-treated group showed a significant decrease in
      erythrocyte, platelet, hemoglobin, and hematocrit values and a significant
      increase in total white blood cells, compared to those of controls. While,
      superoxide dismutase, catalase, glutathione, and vitamin C values were decreased
      by potassium bromate treatment, lipid peroxidation (as malondialdehyde) and
      erythrocyte osmotic fragility values were increased. Interestingly, potassium
      bromate treatment showed significant genotoxic effects, as demonstrated by DNA
      degradation. These changes were confirmed by blood smears histopathological
      observations which were marked by a necrosis and a decrease of erythrocytes
      number. A. corallinum extract appeared to be effective against hematotoxic and
      genotoxic changes induced by potassium bromate, as evidenced by the improvement
      of the parameters cited above.

PMID- 24913102
TI  - Iraq and Afghanistan War Veterans with Reintegration Problems: Differences by
      Veterans Affairs Healthcare User Status.
AB  - We studied 1,292 Iraq and Afghanistan War veterans who participated in a clinical
      trial of expressive writing to estimate the prevalence of perceived reintegration
      difficulty and compare Veterans Affairs (VA) healthcare users to nonusers in
      terms of demographic and clinical characteristics. About half of participants
      perceived reintegration difficulty. VA users and nonusers differed in age and
      military background. Levels of mental and physical problems were higher in VA
      users. In multivariate analysis, military service variables and probable
      traumatic brain injury independently predicted VA use. Findings demonstrate the
      importance of research comparing VA users to nonusers to understand veteran
      healthcare needs. 

PMID- 24913104
TI  - Protein kinase CK2 and angiogenesis.
AB  - CK2 is an ubiquitously expressed protein kinase, which is composed of two
      catalytic a- and a'- and two noncatalytic b-subunits. CK2 protein levels and
      kinase activity is elevated in rapidly proliferating cells including cancer
      cells. There is increasing evidence that CK2 also plays an essential role in
      angiogenesis, either by interaction or phosphorylation of growth factors or by
      phosphorylation or binding to proteins in signalling cascades, which are
      implicated in angiogenesis. Over the last ten years a great number of inhibitors
      for CK2 were detected, two of them are now in clinical phase II trials for the
      treatment of cancer patients. Some of these inhibitors were also found to be
      active in the inhibition of angiogenesis. Thus, CK2 inhibitors probably together
      with inhibitors of other signalling molecules involved in angiogenesis might be
      powerful tools for the treatment of cancer and cancer connected angiogenesis. 

PMID- 24913103
TI  - Use of administrative and electronic health record data for development of
      automated algorithms for childhood diabetes case ascertainment and type
      classification: the SEARCH for Diabetes in Youth Study.
AB  - BACKGROUND: The performance of automated algorithms for childhood diabetes case
      ascertainment and type classification may differ by demographic characteristics.
      OBJECTIVE: This study evaluated the potential of administrative and electronic
      health record (EHR) data from a large academic care delivery system to conduct
      diabetes case ascertainment in youth according to type, age, and race/ethnicity.
      SUBJECTS: Of 57 767 children aged <20 yr as of 31 December 2011 seen at
      University of North Carolina Health Care System in 2011 were included. METHODS:
      Using an initial algorithm including billing data, patient problem lists,
      laboratory test results, and diabetes related medications between 1 July 2008 and
      31 December 2011, presumptive cases were identified and validated by chart
      review. More refined algorithms were evaluated by type (type 1 vs. type 2), age
      (<10 vs. >=10 yr) and race/ethnicity (non-Hispanic White vs. 'other').
      Sensitivity, specificity, and positive predictive value were calculated and
      compared. RESULTS: The best algorithm for ascertainment of overall diabetes cases
      was billing data. The best type 1 algorithm was the ratio of the number of type 1
      billing codes to the sum of type 1 and type 2 billing codes >=0.5. A useful
      algorithm to ascertain youth with type 2 diabetes with 'other' race/ethnicity was
      identified. Considerable age and racial/ethnic differences were present in type
      non-specific and type 2 algorithms. CONCLUSIONS: Administrative and EHR data may
      be used to identify cases of childhood diabetes (any type), and to identify type
      1 cases. The performance of type 2 case ascertainment algorithms differed
      substantially by race/ethnicity.

PMID- 24913105
TI  - Expression of the PAR-1 protein on the surface of platelets in patients with
      chronic peripheral arterial insufficiency - preliminary report.
AB  - BACKGROUND: The activation of pro-coagulation mechanisms associated with the
      vascular wall's immune and inflammatory responses wall to injury plays a crucial
      role in the mechanisms of the induction and progression of atherosclerosis.
      OBJECTIVES: The aim of this study was to determine the role of protease activated
      receptors (PAR-1) expressed on the surface of blood platelets in the pathogenesis
      of chronic peripheral arterial obliterative disease (PAOD) in patients with
      obliterative atherosclerosis (n = 24) and diabetic macroangiopathy (n = 16), as
      well as in the controls (n = 12). MATERIAL AND METHODS: In addition to the
      expression of PAR-1, serum/plasma concentrations of thrombin-antithrombin complex
      (TAT), the von Willebrand factor (vWF), the platelet-derived growth factor,
      monocyte chemotactic protein, the soluble form of the platelet endothelial cell
      adhesion molecule, thrombin activatable fibrinolysis inhibitor and interleukin 6
      (IL-6) were determined. RESULTS: Compared to the controls, PAOD patients were
      characterized by significantly higher levels of PAR-1 expression, vWF, TAT and IL
      6. Individuals with diabetic macroangiopathy did not differ significantly from
      individuals with obliterative atherosclerosis in terms of PAR-1 expression. Upon
      activation with thrombin receptor antagonist peptide (TRAP), the levels of PAR-1
      were comparable in all analyzed groups. In patients with diabetic
      macroangiopathy, a significant association was observed between the expression of
      PAR-1 on the surface of the platelet and the serum TAT concentration, as well as
      between TAT and serum IL-6 concentration. CONCLUSIONS: Enhanced expression of PAR
      1 on the thrombocyte surface in chronic PAOD patients occurs equally in cases of
      diabetic macroangiopathy and in individuals free from this endocrine pathology.

PMID- 24913107
TI  - Growth dynamics of the triceps brachii muscle in the human fetus.
AB  - BACKGROUND: The triceps brachii muscle, the strongest extensor of the elbow
      joint, is characterized by the three heads: long, lateral and medial. OBJECTIVES:
      In the present study we aimed to examine the linear parameters (length, width) of
      the fetal triceps brachii muscle and to provide their growth dynamics. MATERIAL
      AND METHODS: Using anatomical dissection, digital image analysis (Multiscan
      v.14.02), and statistics (Student's t-test, regression analysis) we measured in
      mm the length and width of the triceps brachii in 30 fetuses of both sexes
      (12?,18?) aged 12-29 weeks. RESULTS: Neither sex nor laterality differences were
      found. All the parameters studied increased proportionately with age. The linear
      functions were computed as follows: y = 6.797 + 2.079 x Age (r = 0.886) for
      length of the long head's belly, y = - 0.041 + 0.215 * Age (r = 0.786) for width
      of the long head's belly, y = 1.889 + 0.174 * Age (r = 0.796) for length of the
      long head's proximal tendon, y = 0.158 + 0.052 * Age (r = 0.864) for width of the
      long head's proximal tendon, y = 5.270 + 1.809 * Age (r = 0.855) for length of
      the lateral head's belly, y = 0.348 + 0.284 * A ge (r = 0.829) for width of the
      lateral head's belly, y = 0.942 + 1.837 * Age (r = 0.839) for length of the
      medial head's belly, y = 0.314 + 0.234 * Age (r = 0.852) for width of the medial
      head's belly, y = - 3.191 + 0.984 * Age (r = 0.929) for lenght of the common
      tendon, and y = - 0.478 + 0.133 * Age (r = 0.933) for width of the common tendon.
      CONCLUSIONS: Neither male-female nor right-left differences are observed in
      morphometric parameters of the triceps brachii muscle. The long head's belly is
      the thinnest, while the lateral head's belly is the widest one. The long head is
      the longest and the medial head is the shortest one. The developmental dynamics
      of the triceps brachii muscle follow proportionately.

PMID- 24913106
TI  - Interaction of sertraline and nimodipine on some behavioural tests in rats.
AB  - BACKGROUND: Intracellular calcium contributes to the development of affective
      disorders. Also, calcium channel inhibitors influence the activity of many
      neurotransmitters and exert antidepressant and anxiolytic properties. OBJECTIVES:
      The aim of this study was to examine the effects of sertraline on anxiety and
      depressive behaviors and the role of nimodipine, a calcium channel antagonist, on
      these effects. MATERIAL AND METHODS: Forced swimming and elevated plus maze tests
      were used to assess depression and anxiety respectively in rats. Sertraline (10
      mg/kg) was administered repeatedly for 7 days both alone and in combination with
      single (0.5 mg/kg) and repeated (0.5 mg/kg/7 days) nimodipine administrations.
      RESULTS: Both repeated sertraline (S) and its combination with single nimodipine
      administration (S + N) significantly decreased the immobility time compared to
      control. The combination of (S) with repeated doses of nimodipine (N/7d),
      significantly increased the immobility time compared to (S) and (S + N). Single
      dose of nimodipine (N) significantly increased the immobility time compared to
      (S) and (S + N), and decreased the number of divings compared to control. There
      was no significant difference between groups in terms of struggle and the time
      spent in closed arms of the elevated plus maze. CONCLUSIONS: There was no
      interaction between a single dose of sertraline and nimodipine when administered
      in combination, while repeated nimodipine administration reversed the
      antidepressant-like effect of sertraline. We suggest that L-type calcium channels
      are involved in the antidepressant-like effect of sertraline. Neither single nor
      repeated nimodipine administration had a significant effect on both depressive
      behaviour and anxiety. We also propose that there is no interaction between the
      effects of sertraline and nimodipine on anxitey behavior.

PMID- 24913108
TI  - Relevance of serology for Mycoplasma pneumoniae infection among children with
      persistent cough.
AB  - BACKGROUND: Mycoplasma pneumoniae is an important cause of upper and lower
      respiratory tract infections. Cough and tracheobronchitis are the commonest
      features of M. pneumoniae infection but diagnosis based on clinical symptoms that
      may be due to other respiratory pathogens is impossible. Thus laboratory testing
      for M. pneumoniae is particularly important. Correct and rapid diagnosis of M.
      pneumoniae infections is of prime importance to introduce appropriate antibiotic
      treatment. OBJECTIVES: Evaluation of the incidence of IgM and IgG antibodies
      specific to M. pneumoniae among children with pneumonia and/or chronic cough.
      MATERIAL AND METHODS: Serum samples from 148 children with a history of chronic
      cough (lasting at least one month), recurrent respiratory tract infections,
      allergic rhinitis, and/or inflammatory changes on X-chest ray. First, all sera
      were screened for specific anti-M. pneumoniae antibodies using agglutination test
      following the detection of specific IgM and IgG anti-M. pneumoniae antibodies
      using immunoenzymatic assays. RESULTS: Out of the 148 serum samples, 57 (38.5%)
      gave positive screening results. However, the presence of M. pneumoniae-specific
      IgM and/or IgG antibodies was confirmed by immunoenzymatic assays in only 30
      (52.6%) of these 57 positive samples. These results indicated that in as many as
      27 (47.4%) out of the 57 serum samples screened, false-positive results occurred.
      CONCLUSIONS: Evaluation of acute- and convalescent-phase sera is necessary to
      make possible accurate interpretation of the serological testing results.

PMID- 24913109
TI  - Identifying EGFR mutations from SCLC patient plasma by mutant-enriched liquidchip
      technology.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKI) such as erlotinib and gefitinib are targeted drugs for the kinase domain of
      EGFR. They are widely used for the treatment of non-small cell lung cancer
      (NSCLC). The EGFR exon 19 deletion mutation and the L858R mutation in exon 21
      comprise approximately 90% of the somatic mutations in NSCLC patients that
      respond to EGFR TKI. Several recent studies have also reported that small cell
      lung cancer (SCLC) patients with EGFR mutations responded to gefitinib. Further
      study, however, has been limited due to the difficulty obtaining tumor specimens
      from SCLC patients. OBJECTIVES: The aim of this study was to explore the EGFR
      mutation status in SCLC patients by plasma analysis. MATERIAL AND METHODS: Plasma
      samples from SCLC patients were collected for mutant-enriched liquidchip (MEL)
      analysis to identify the EGFR mutations in exon 19 and 21. RESULTS: The exon 19
      deletion mutation was detected in one out of 35 patients (a female non-smoker).
      No exon 21 mutations were found. CONCLUSIONS: A prevalence of EGFR mutations in
      SCLC is rare, and occurs most frequently in females and nonsmokers.

PMID- 24913110
TI  - The diagnostic value of C-reactive protein in bacterial translocation in
      experimental biliary obstruction.
AB  - BACKGROUND: Many experimental studies have verified that obstructive jaundice
      (OJ) causes bacterial translocation (BT). OBJECTIVES: The aim of this study was
      to assess to whether C-Reactive Protein (CRP) can be used to detect bacterial
      translocation induced by biliary obstruction. MATERIAL AND METHODS: Twenty rats
      were divided into two groups containing 10 rats each: sham-operated controls and
      the obstructive jaundice (OJ) group. All procedures were performed aseptically.
      After an upper midline incision, the common bile duct (CBD) was identified,
      mobilized, ligated and divided. The sham-operated animals had a similar incision,
      followed by mobilization of the CBD, without ligation or division. Ten days after
      the first operation, a second laparotomy was performed. Blood samples were
      collected for culture and serum CRP analysis. In addition, liver, spleen, and
      mesenteric lymph node (MLN) specimens were taken for microbiological culture to
      determine the presence of BT. BT was considered positive if there was any
      bacterial growth in the MLN, liver, spleen, or blood cultures; a lack of
      bacterial growth indicated a negative BT. RESULTS: The OJ group had significantly
      higher rates of bacterial translocation than the sham-operated group (p = 0.002).
      Mean CRP levels (ng/mL) were 8.7 +/- 11.8 and 18.6 +/- 17.2 in the sham-operated
      group and the OJ group respectively. There was no significant difference in mean
      CRP levels between the two groups (p = 0.257). Mean CRP levels were 4.5 +/- 4.3
      and 24.9 +/- 16.4 in the BT (-) and BT (+) groups respectively (p = 0.003). A
      marked increase in CRP levels paralleled an increase in BT. CONCLUSIONS: This
      study has demonstrated a direct relationship between BT and CRP levels in an
      experimental OJ model.

PMID- 24913111
TI  - The impact of selected preparations of trace elements - magnesium, potassium,
      calcium, and zinc on the release of diclofenac sodium from enteric coated tablets
      and from sustained release capsules.
AB  - BACKGROUND: In an aging society, many patients require long-term treatment. This
      fact is associated clearly with the simultaneous occurrence of lifestyle diseases
      such as hypertension, diabetes, and even osteoarthritis. Concomitant medications,
      which are a common practice, pose a major threat of an interaction between these
      drugs. Very popular now "fast way of life" that makes people have less and less
      time to prepare well-balanced meals of high nutritional value. The result of this
      lifestyle is an increased need for supplementation preparations necessary
      vitamins and minerals. Given the wide availability of dietary supplements (shops,
      kiosks, petrol stations) raises the question about the possibility of an
      interaction between the uncontrolled intake of dietary supplements and
      medications received in the most common diseases of civilization. OBJECTIVES: The
      aim of this study was to investigate the effect of the most important minerals
      (magnesium, potassium, calcium, zinc) contained in the popular nutritional
      supplements, the release also often used as an anti-pain, anti-inflammatory,
      diclofenac sodium from the different formulations. RESULTS: Among the many as
      sodium diclofenac selected two most common: film-coated tablets and sustained
      release capsules. The study showed a significant effect of minerals on the
      release of diclofenac sodium and differences that impact, depending on the test
      form of the drug.

PMID- 24913112
TI  - Gene-gene interaction of ACE I/D, endothelial nitric oxide synthase 4 a/b and
      ApoE does not affect coronary artery disease severity.
AB  - OBJECTIVES: Previous studies have shown the impact of angiotensin converting
      enzyme (ACE) insertion/deletion (I/D), endothelial nitric oxide synthase (eNOS)
      polymorphisms and ApoE genotypes on coronary artery disease (CAD). The aim of
      this study is to investigate the relationship between the genetic polymorphisms
      and the severity of CAD and to evaluate their potential interactions. MATERIAL
      AND METHODS: All patients underwent coronary angiography; coronary score (CS) and
      severity score (SS) were calculated for them. ACE I/D, eNOS and ApoE
      polymorphisms were detected by polymerase chain reaction (PCR). RESULTS: Neither
      CS nor SS showed a direct relationship with eNOS and ApoE genotypes. CS and SS
      were found to be high in patients carrying the ACE DD allele (p = 0.034 and p =
      0.009). In the gene interactions, there was an increase in the SS only in
      patients with coexisting eNOS b/b genotype and ACE DD allele (p = 0.043).
      CONCLUSIONS: The interactions of the gene polymorphisms investigated don't play
      an important role in determining an individual's risk for the severity of CAD.

PMID- 24913113
TI  - Prevalence of xerostomia and the salivary flow rate in diabetic patients.
AB  - BACKGROUND: Diabetes is a metabolic disease characterized by hyperglycemia, which
      results from relative or absolute insulin deficiency. One of the first oral
      symptoms of diabetes is xerostomia. OBJECTIVES: The aim of the study was to
      determine the prevalence of the xerostomia symptoms and salivary flow rate in
      diabetic patients according to the type of diabetes, the level of metabolic
      control and the duration of the disease. MATERIAL AND METHODS: The study involved
      156 adult patients of both sexes including 34 patients with diabetes type 1
      (group C1), 59 with diabetes type 2 (group C2), and 63 generally healthy
      individuals as two control groups, sex- and age-matched to the diabetic group.
      The patients suffering from both types of diabetes were additionally subdivided
      according to the level of metabolic control and the duration of the disease.
      Xerostomia was diagnosed with the use of a specially prepared questionnaire and
      Fox's test. Moreover, the salivary flow rate of resting mixed saliva was
      measured. RESULTS: In type 1 diabetics, a significantly lower salivary flow rate
      in comparison to the age-matched control group (0.38 +/- 0.19 mL/min vs. 0.53 +/-
      0.20 mL/min, p < 0.01) was found. However in type 2 diabetics, a slight lower
      salivary flow rate was noticed (on average, 20% lower). Dry mouth was far more
      frequently diagnosed in type 1 diabetics than in the control group. CONCLUSIONS:
      In type 1 diabetics, in comparison to healthy subjects, a significantly lower
      resting flow rate of saliva and significantly higher prevalence of xerosomia were
      observed, but in type 2 diabetics, only a trend of such variability was observed.

PMID- 24913114
TI  - The occurrence of Al amyloidosis (light-chain amyloidosis) in patients with
      multiple myeloma in Lower Silesia Region, Poland.
AB  - BACKGROUND: The incidence of amyloidosis is difficult to determine because the
      disease is often undiagnosed or diagnosed incorrectly. In Polish studies, there
      are no statistics and analyses of the factors that may influence the development
      of amyloidosis in patients with multiple myeloma. OBJECTIVES: The goal of this
      study was to estimate the incidence of AL amyloidosis in MM patients in Lower
      Silesia region. MATERIAL AND METHODS: 70 patients treated at the Department of
      Hematology, Provincial Hospital in Legnica and the Department of Hematology,
      Blood Neoplasm and Bone Marrow Transplantation, Medical University in Wroclaw
      were enrolled in the survey. 37 patients were newly diagnosed, 33 had been
      treated for 2-34 months. The basis for the diagnosis of amyloidosis was the
      presence of green colored amyloid deposits in the polarized light microscope in
      the adipose tissue (received from abdominal fold and stained with Congo red).
      RESULTS: Amyloidosis was diagnosed in 18 (25.7%) patients with MM, 9/9 F /M, aged
      47-83 years. 6 (33%) pts with amyloidosis had newly diagnosed MM, in 12 (67%)
      progression of the disease was diagnosed. Amyloidosis occurred significantly more
      often (p = 0.048) in already treated patients. The odds ratio (OR) was 2.95.
      Amyloidosis occurred most frequently in patients with IgG myeloma (67%), (OR =
      1.98), was more often found in patients with kappa light chain versus lambda,
      respectively 67% and 33%. The probability of amyloidosis in patients with
      clinical stage III was 1.5 times higher (p = 0.05) than in other stages (OR =
      1.5), in persons with renal dysfunction was twice as high (OR = 2.4) compared to
      the renal competence group (p = 0.05). CONCLUSIONS: AL amyloidosis in the course
      of MM occurs in Lower Silesia region with a comparable rate to other regions of
      the world. It is significantly more often diagnosed in patients with relapsed or
      refractory disease, in persons with clinical stage III and with renal failure.

PMID- 24913115
TI  - Analysis of the prevalence of medicines and psychoactive substances among drivers
      in the material of the Department of Forensic Medicine at the Medical University
      of Bialystok.
AB  - OBJECTIVES: To evaluate the prevalence of medicines and psychoactive substances
      in the blood of drivers. MATERIAL AND METHODS: The data, recorded in 2010-2011,
      was comprised of 274 blood samples of sober drivers (269 men and 5 women). 126
      drivers within the group died immediately on the spot (mean age 29.7 years, range
      19-53 years), 31 drivers survived the accident (mean age 32.4 years, range 24-69
      years), and 117 drivers were stopped for traffic control (mean age 26.4 years,
      range 17-49 years). ELISA immuno-enzymatic blood tests detecting medicines and
      psychoactive substances were performed by the Neogen company. The presence of the
      tested substances was confirmed by gas chromatography and liquid chromatography
      with a mass detector (GC/MS and LC/MS). RESULTS: From the total number of 274
      individuals, the presence of psychoactive substances was found in 132 cases,
      which accounted for 48.2% of all subjects. The drivers found to be under the
      influence of medicines and psychoactive substances were most often stopped for a
      roadside survey, among whom the percentage of positive results was 92.3% (108
      cases out of 117 subjects). Among the total number of positive findings the
      psychoactive substances used, alone or in combination with other agents, were
      tetrahydrocannabinols (42.4%), amphetamines (26.5%), opiates (25.7%) and
      benzodiazepines (15.1%), and their concentration in the blood did not exceed
      toxic levels. CONCLUSIONS: In the group of psychoactive substances most often
      used, either alone or in combination with other agents, there were
      tetrahydrocannabinols, whose high percentage of positive results in drivers
      stopped for a roadside control may be explained by commissioning studies on early
      screening. Concentrations of the substances in most cases did not exceed toxic
      levels. Roadside examinations, on the basis of their alcohol-like effect, were
      performed primarily on male drivers.

PMID- 24913116
TI  - Risk factors for intraaortic balloon pump use in coronary artery bypass surgery.
AB  - OBJECTIVES: The study was aimed at investigating the risk factors of using an
      intraaortic balloon pump (IABP) in coronary artery bypass surgery and presenting
      the authors' clinical experience of IABP use. MATERIAL AND METHODS: The study
      included 1094 patients who underwent coronary artery bypass surgery at the
      authors' clinic between January 2009 and December 2011. A comparison was made
      between 17 patients in whom an IABP was used and 1077 patients in whom it was not
      used. RESULTS: An intraaortic balloon pump was used in 17 patients (1.55%) out of
      1094 patients who underwent isolated coronary artery bypass surgery. The ratio of
      patients who had had preoperative myocardial infarction within the preceding 30
      days, left main coronary artery stenosis of more than 50% and emergency surgery
      in Group 1 were higher than in Group 2 (p < 0.05). The total cardiopulmonary
      bypass time of Group 1 was found to be longer than that of Group 2 (p < 0.05).
      The demand for inotropics after weaning from cardiopulmonary bypass was greater
      in Group 1 than in Group 2 (p < 0.05). The need for reoperation (because of
      bleeding) was higher in Group 1 than in Group 2 (p < 0.05). The patients' stay on
      the intensive care unit was longer in Group 1 than in Group 2 (p < 0.05).
      Mortality rates were 29.4% in Group 1 and 1.2% in Group 2 (p < 0.05).
      CONCLUSIONS: Preoperative myocardial infarction within the preceding 30 days,
      left main coronary artery stenosis of more than 50%, emergency surgery and long
      cardiopulmonary bypass time are important risk factors for IABP use in coronary
      artery bypass surgery.

PMID- 24913117
TI  - Trace elements, magnesium, and the efficacy of antioxidant systems in children
      with type 1 diabetes mellitus and in their siblings.
AB  - BACKGROUND: Magnesium (Mg), selinium (Se), zinc (Zn), manganese (Mn), and copper
      (Cu) are involved in the mechanisms of antioxidant defense. Mn and Cu, which
      participate in the generation of reactive oxygen species (ROS), also have pro
      oxidative properties. OBJECTIVES: To evaluate the levels of Mg, Se, Zn, Mn, and
      Cu, as well as the effectiveness of antioxidant defense mechanisms in children
      with Type 1Diabetes Mellitus (T1DM) and in their siblings. The preliminary
      findings were originally reported in 2009 at the 35th annual conference of the
      International Society for Pediatric and Adolescent Diabetes (ISPAD) in Ljubljana,
      Slovenia. MATERIAL AND METHODS: The study involved 87 children with T1DM, 2-19
      years old, treated for T1DM for an average of 3.5 years. The sibling and control
      groups comprised 27 and 41 children, aged 4.5-16.5 years and 10.5-18 years
      respectively. The parameters named above were assessed in relation to metabolic
      compensation levels (HbA1C) and disease duration. RESULTS: Compared with the
      control group, T1DM children had lower plasma levels of Mg and Zn and higher
      levels of Cu; the siblings had lower levels of Zn; T1DM children had lower
      copper/zinc superoxide dismutase (CuZnSOD) activity; and both T1DM children and
      their siblings had higher catalase (CAT) activity and lower total antioxidant
      status (TAS) levels. CONCLUSIONS: There may be a correlation between impaired
      antioxidant status and Mg and Zn deficiency and increased Cu levels in T1DM
      children. Oxidative stress in T1DM is accompanied by alterations in enzymatic
      activity and non-enzymatic mechanisms of antioxidant defense. The decreased TAS
      levels noted in T1DM patients may impair the effectiveness of non-enzymatic
      antioxidant systems. The increased CAT activity and unimpaired selenium-dependent
      glutathione peroxidase (Se-GSHPx) activity point indirectly to enhanced ROS
      generation in T1DM children. The impaired antioxidant defense found in the
      siblings of T1DM patients may indicate that genetic factors play a role.

PMID- 24913118
TI  - Medical complications and patient outcomes in Iranian veterans with spinal cord
      injury.
AB  - BACKGROUND: Spinal cord injury [SCI] occurring in military veterans is a
      disabling and highly morbid event. Often the victims are young active males who
      sustain these injuries during military conflict and suffer from the complications
      of the SCI for the rest of their lives. OBJECTIVES: The aim of the study is to
      report the epidemiology of Iranian SCI veterans and their health related quality
      of life, medical complications and patient associated outcomes. MATERIAL AND
      METHODS: A cohort of 1984 patients was examined to investigate the epidemiology
      of Iranian SCI veterans of the Iraq-Iran War (1980-1988); 1803 out of the total
      number of SCI records were included. Health monitoring was carried out through
      scheduled monthly visits by general physicians, followed by interviews with
      specialists from March 20, 2007, to March 19, 2010. Additional follow-up was
      conducted by telephone survey. RESULTS: In all, 174 patients (8.77%) had
      incomplete injury and the rest had complete injury. the most frequent level of
      injury was the thoracic level (1256 patients - 63.30%). Pressure ulcers were the
      most frequent complication (up to 14.7% annual prevalence), followed by reactions
      to severe stress and adjustment disorders (up to 13.6%) and diabetes (up to
      10.1%). In the telephone surveys, kidney and/or urologic disorders were the most
      frequent reported complaints (21.6%). A total of 101 out of the 1984 SCI veterans
      died between 2000 and 2010 (~0.5% per year). CONCLUSIONS: In veterans with spinal
      cord injury, pressure area ulcers (ICD10:L89), reactions to severe stress and
      adjustment disorders (ICD10:F43), diabetes mellitus (ICD10:E10-E14) and kidney
      and/or urologic disorders are common and should be addressed aggressively in
      healthcare planning and management programs for patients with spinal cord
      injuries.

PMID- 24913119
TI  - Successful treatment of pilonidal disease by intense pulsed light device.
AB  - BACKGROUND: Pilonidal disease is foreign body reactions accompanied by chronic
      inflammation that most commonly arises in the hair follicles of the natal cleft
      or other hair-bearing areas. Today, surgical intervention remains the treatment
      of choice. But surgical treatment is an invasive method with a high failure rate
      and recurrence. OBJECTIVES: The authors' objective was to assess the efficacy of
      intense pulsed light (IPL) device on pilonidal disease. MATERIAL AND METHODS:
      This case series study was carried out between 2008 and 2012 on patients with
      pilonidal sinus in Qazvin university of Iran. All patients received 6 session
      treatments with IPL hair removal with 4-6 weeks interval until most of the hair
      was removed. This was repeated 2.5 +/- 0.3 years after treatment. In cases with
      acute phase pilonidal sinus histopathological examination was done. RESULTS: IPL
      hair removal procedure was performed on 30 patients with their ages ranging from
      16 to 41 years, with a mean (SD) of 23.1 (6.2) years. In this study 13 patients
      were presented with acute and 6 patients were presented with chronic phase. 11
      patients had a positive history of one surgical treatment and presented
      recurrences. The overall recurrence rate after IPL treatment in this study was
      seen in 4 (13.3%) patients. The histopathological examination of our study showed
      that the hair fragments create a foreign body type granulomatous inflammatory
      reaction. This process could be triggering factor of the disease. CONCLUSIONS:
      IPL hair removal in affected area could be an alternative treatment to surgery or
      a choice treatment post surgery to decrease recurrence rate.

PMID- 24913120
TI  - An evaluation of the effectiveness of external urethral meatus incision in girls
      with an anterior deflected urinary stream and symptoms of detrusor overactivity.
AB  - BACKGROUND: Urethral stenosis or abnormalities in the external urethral meatus in
      girls may lead to serious functional bladder outlet obstruction and recurrent
      urinary tract infections. OBJECTIVES: The aim of the study was to analyze the
      efficacy of meatotomy in girls with an anterior deflected urinary stream (ADUS)
      and symptoms of detrusor overactivity. MATERIAL AND METHODS: A group of 67 girls
      between the ages of 5 and 16 (mean age: 8.6 years) with symptoms of detrusor
      overactivity participated in the study. The girls were treated with oxybutinin in
      the years 2010-2011. The group included 37 girls with ADUS (the ADUS group) while
      the remaining 30 girls (the OXY group) were found to have a normal urinary
      stream. In the ADUS group an external urethral meatus incision was performed. The
      follow-up period was three months. The presence of urinary tract infections (UTI)
      as well as nocturnal bedwetting and daytime incontinence were analyzed before and
      after treatment. RESULTS: After three months, in the ADUS group no UTI was found
      in 12 children (32%) (p < 0.05), including 11 patients with prior febrile UTI (p
      < 0.05). Recovery from daytime urinary incontinence was observed in 20 girls
      (54%) and recovery from nocturnal bedwetting in 8 girls (22%). In the OXY group
      no infections were found in three girls (10%); recovery from daytime urinary
      incontinence was noted in 21 girls (70%) and from nocturnal bedwetting in 10
      girls (33%). CONCLUSIONS: Girls with symptoms of detrusor overactivity
      accompanied by an anterior deflected urinary stream experience UTIs and fever
      more often than girls with detrusor overactivity and a normal urinary stream. An
      incision in the external urethral meatus in girls with ADUS and detrusor
      overactivity seems to be effective treatment for recurrent urinary tract
      infections, especially febrile ones.

PMID- 24913121
TI  - Morphometry in the cytological diagnosis of cervical smears.
AB  - BACKGROUND: Morphometry of cells found in normal and abnormal smears taken from
      the vagina and the uterine cervix is the assessment of the size and diameter of
      their nuclei. The values of these quantities provide information on the origin of
      these cells and the degree of possible anomalies. Determining the morphometric
      traits of different types of cells found in the cervix and the uterus is a very
      important element in the diagnosis of disorders that often lead to cervical
      tumors. OBJECTIVES: The aim of this research is to determine the morphometric
      characteristics of cells found in cervical smears by measuring the cell
      circumference, the diameter of the nucleus and the cell surface areain order to
      identify which clinical group the cells belong to, which facilitates diagnosis.
      MATERIAL AND METHODS: The study material consisted of cervical smears that
      demonstrated the presence of cells in various phases of the clinical Bethesda
      classification. For each clinical classification, the values of the cell
      circumference, the cell surface area and the diameter of the nucleus were
      measured for 100 cells. RESULTS: The largest cells are normal cells in the
      surface layer. In relation to these cells, the atrophic cells from the groups
      containing atypical squamous cells of undetermined significance (ASC-US), low
      grade squamous intraepithelial lesions (LSIL), high-grade squamous
      intraepithelial lesion (HSIL) and tumor cells tend to decrease in size, with
      small variations. Considering the mean values of the parameters analyzed, the
      cells of the LSIL group are larger than those from the ASC-US group. According to
      the mean values, normal cells have the smallest nucleus and the HSIL cells and
      tumor cells have the largest. CONCLUSIONS: The statistical analysis shows
      significant differences between the morphometric traits in the different clinical
      groups, which indicates that morphometry can be used in cytological diagnosis.

PMID- 24913122
TI  - Demodex - an old pathogen or a new one?
AB  - Demodex was first identified over 150 years ago, but only recently has it
      attracted wider interest as a contributor to chronic diseases such as acne
      rosacea or marginal blepharitis. Demodex is commonly found in the human
      population, in skin sebaceous glands or follicles. The frequency of Demodex
      infection increases with age, as it is mainly diagnosed after the age of seventy;
      however, it can sometimes be found in children and teenagers. Demodex is supposed
      to contribute to the development of marginal blepharitis or acne rosacea, but the
      pathogenic mechanisms have not yet been explained in detail. These diseases are
      chronic and the long-term treatment effects are not satisfactory. This paper
      presents the characteristics of Demodex as well as its prevalence in the
      pathogenesis of eye and skin diseases, and describes the diagnostics and
      treatment of these disorders. 

PMID- 24913123
TI  - The role and application of exfoliative cytology in the diagnosis of oral mucosa
      pathology - contemporary knowledge with review of the literature.
AB  - On the basis of the current available literature, the authors have presented a
      short description of cytological examination and its application in the oral
      mucosa disease diagnostic process. Furthermore, the advantages and disadvantages
      of this method are described. The available diagnostic tools used for oral smears
      were reviewed as well as more and more often available methods which aim at
      making the diagnosis process more accurate and more favorable for patients. Oral
      cytology analysis may, in the near future, be a very useful examination for
      patients in terms of diagnostics and monitoring, not only during the treatment
      but also afterwards. The authors would like to demonstrate what a beneficial tool
      this cytological examination could be as a fast and cheap cancer prophylactic
      test. This opinion is based on the fact that this cytological method has
      significantly improved the detection of uterine cervical cancer during a
      gynecological examination since the introduction of the Papanicolau technique in
      the 40s. 

PMID- 24913124
TI  - Anal warts (condylomata acuminata) - current issues and treatment modalities.
AB  - HPV infections are currently the most frequent cause of genital infections in the
      USA. Risk factors are early onset of sexual activity, multiple sexual partners, a
      history STDs, an early age of first pregnancy and tobacco use. In the past, HPV
      viruses were thought to be STDs, but it is now known that penetration is not
      necessary. Skin-to-skin or mucosa-to-mucosa contact is enough to transmit the
      virus, which presents high tropism for those tissues. The Papillomaviridae family
      includes over 120 viruses, some of which have high malignant transformation
      rates. The most common malignancy connected to HPV is uterine cervix cancer and
      anal canal cancer. The range of morphology of perianal lesions means that a
      thorough clinical examination is required, including an anoscopy. Therapeutic
      modalities often seek to eliminate macroscopic changes rather than focus on the
      cause of the infection, which leads to a high recurrence rate. Externally located
      changes can be eliminated with patient-applied treatments. Those located in the
      anal canal and distal end of the rectal ampulla require treatment by a qualified
      medical provider. Due to the high recurrence rate after standard treatment,
      special attention has been given to vaccinations. The polyvalent vaccine includes
      HPV viruses with both low and high malignant transformation risk. This has led to
      a decrease in the rate of malignancies. 

PMID- 24913125
TI  - LcWRKY5: an unknown function gene from sheepgrass improves drought tolerance in
      transgenic Arabidopsis.
AB  - KEY MESSAGE: The expression of LcWRKY5 was induced significantly by salinity,
      mannitol and cutting treatments. Arabidopsis- overexpressing LcWRKY5 greatly
      increased dehydration tolerance by regulating the expression of multiple stress
      responsive genes. Based on the data of sheepgrass 454 high-throughout sequencing
      and expression analysis results, a drought-induced gene LcWRKY5 was isolated and
      cloned, and the biological role of the gene has not been reported until now.
      Bioinformatics analysis showed that LcWRKY5 contains one conserved WD domain and
      belongs to the group II WRKY protein family. LcWRKY5 shows high sequence identity
      with predicted or putative protein products of Hordeum vulgare, Aegilops
      tauschii, Triticum aestivum, Brachypodium distachyon, Oryza sativa, but it has
      low homology with WRKYs from dicotyledonous plants. Several drought-inducibility,
      fungal elicitor, MeJA-responsiveness, endosperm, light, anoxic specific
      inducibility, and circadian control elements were found in the promoter region of
      LcWRKY5. Tissue-specific expression patterns showed that LcWRKY5 is expressed in
      roots and leaves, without expression in other tissues. The expression of LcWRKY5
      was induced significantly under salinity and mannitol stresses but was not
      notably changed under cold and Abscisic acid stress. The LcWRKY5 protein exhibits
      transcription activation activity in the yeast one-hybrid system. Overexpressing
      LcWRKY5 exhibited increased rates of cotyledon greening and plant survival in
      transgenic Arabidopsis compared with wild-type plants under drought stress, and
      the expression levels of DREB2A and RD29A in transgenic plants were enhanced
      under drought stress. These results indicated that LcWRKY5 may play an important
      role in drought-response networks through regulation of the DREB2A pathway.
      LcWRKY5 can be a candidate gene for engineering drought tolerance in other crops.

PMID- 24913127
TI  - CD4+ and CD8+ skin-associated T lymphocytes in canine atopic dermatitis produce
      interleukin-13, interleukin-22 and interferon-gamma and contain a CD25+ FoxP3+
      subset.
AB  - BACKGROUND: T Cells play a major role in the immunopathogenesis of canine atopic
      dermatitis (cAD). However, the significance of cutaneous regulatory T cells
      (Tregs) and CD8(+) T cells is currently unclear. HYPOTHESIS/OBJECTIVES: The study
      aimed to evaluate the presence and distribution of Tregs in cAD and healthy skin
      and to determine the cytokine production of cutaneous CD4(+) and CD8(+) T cells.
      ANIMALS: Biopsies were taken from four dogs with cAD (lesional and nonlesional
      skin) and four healthy control dogs. METHODS: Distribution patterns of T-cell
      subtypes in cAD lesional, nonlesional and control skin were evaluated by
      immunohistochemistry. Phenotypic characterization of T cells from skin explant
      cultures and enzymatic digestions was performed using flow cytometry. Cytokine
      production of sorted CD4(+) and CD8(+) explant-derived T cells was measured by RT
      qPCR. RESULTS: Regulatory T cells phenotypically characterized by CD25(+)
      FoxP3(+) were found in both CD4(+) and CD8(+) subsets of skin explant and
      digestion samples. The percentages of CD4(+) CD25(+) cells that were FoxP3(+)
      were similar in cAD and control skin. In atopic lesional and nonlesional explant
      samples, lower FoxP3(+) percentages of CD8(+) CD25(+) cells were seen compared
      with control skin. The presence of predominantly periadnexal CD25(+) FoxP3(+)
      cells was confirmed by immunohistochemistry in lesional, nonlesional and control
      skin. The CD4(+) /CD8(+) ratio was less than one in cAD skin with both skin
      explant and digestion methods. CD4(+) and CD8(+) T-cell subsets of lesional and
      nonlesional cAD skin were capable of producing interleukin-13, interleukin-22 and
      interferon-gamma. CONCLUSIONS AND CLINICAL IMPORTANCE: Both CD4(+) and CD8(+) T
      cells are likely to contribute to the immunopathogenesis of cAD through the
      production of interleukin-13, interleukin-22 and interferon-gamma. In both
      subsets, functional analysis of FoxP3(+) cells is essential to determine their
      role.

PMID- 24913126
TI  - Transcriptome dynamics of a desert poplar (Populus pruinosa) in response to
      continuous salinity stress.
AB  - KEY MESSAGE: Using RNA sequencing analysis, we identified 9,216 regulatory and
      salt-related genes with differential expression and temporal expression trends
      which provide a clear picture of transcriptomic dynamics in response to
      continuous salinity stress in a desert poplar, Populus pruinosa. Populus pruinosa
      Schrenk is native to the desert region of western China and extraordinarily well
      adapted to the local salt stress. Thus, it is an ideal model for studying plants'
      adaptation to salt stress, but its transcriptomic responses have not been
      previously characterized. Thus, we analyzed time- courses of these responses via
      a series of sequencings. In total, we generated 157.4 million 100 bp paired-end
      clean reads and identified 9,216 differentially expressed genes (DEGs) between
      salt-stressed calli and controls. Gene ontology classification analysis revealed
      that salt stress-related categories--including 'oxidation reduction',
      'transcription factor activity', 'membrane' and 'ion channel activity'--were
      highly enriched among these DEGs. In addition, we grouped the 9,216 DEGs by their
      expression dynamics into four clusters, and the genes in each cluster showed
      enrichment for particular functional categories. We also found that most DEGs
      were activated within 24 h of the stress and their expression stabilized after 48
      h. All these findings suggest that gene expression rapidly and coordinately
      changes during this species' adaptation to salt stress. In addition, the
      identified DEGs provide critical genetic resources for further functional
      analyses and indications of potential transgenic modifications for developing
      salt-tolerant poplars.

PMID- 24913128
TI  - Spontaneous expression of magnetic compass orientation in an epigeic rodent: the
      bank vole, Clethrionomys glareolus.
AB  - Magnetoreception has been convincingly demonstrated in only a few mammalian
      species. Among rodents, magnetic compass orientation has been documented in four
      species of subterranean mole rats and two epigeic (i.e. active above ground)
      species-the Siberian hamster and the C57BL/6J mouse. The mole rats use the
      magnetic field azimuth to determine compass heading; their directional preference
      is spontaneous and unimodal, and their magnetic compass is magnetite-mediated. By
      contrast, the primary component of orientation response is learned in the hamster
      and the mouse, but both species also exhibit a weak spontaneous bimodal
      preference in the natural magnetic field. To determine whether the magnetic
      compass of wild epigeic rodents features the same functional properties as that
      of laboratory rodents, we investigated magnetic compass orientation in the bank
      vole Clethrionomys glareolus (Cricetidae, Rodentia). The voles exhibited a robust
      spontaneous bimodal directional preference, i.e. built nests and slept
      preferentially along the north-south axis, and deflected their directional
      preference according to a shift in the direction of magnetic north, clearly
      indicating that they were deriving directional information from the magnetic
      field. Thus, bimodal, axially symmetrical directional choice seems to be a common
      feature shared by epigeic rodents. However, spontaneous directional preference in
      the bank vole appeared to be more pronounced than that reported in the hamster
      and the mouse. These findings suggest that bank voles are well suited for future
      studies investigating the adaptive significance and mechanisms of magnetic
      orientation in epigeic rodents. 

PMID- 24913129
TI  - Performing private database queries in a real-world environment using a quantum
      protocol.
AB  - In the well-studied cryptographic primitive 1-out-of-N oblivious transfer, a user
      retrieves a single element from a database of size N without the database
      learning which element was retrieved. While it has previously been shown that a
      secure implementation of 1-out-of-N oblivious transfer is impossible against
      arbitrarily powerful adversaries, recent research has revealed an interesting
      class of private query protocols based on quantum mechanics in a cheat sensitive
      model. Specifically, a practical protocol does not need to guarantee that the
      database provider cannot learn what element was retrieved if doing so carries the
      risk of detection. The latter is sufficient motivation to keep a database
      provider honest. However, none of the previously proposed protocols could cope
      with noisy channels. Here we present a fault-tolerant private query protocol, in
      which the novel error correction procedure is integral to the security of the
      protocol. Furthermore, we present a proof-of-concept demonstration of the
      protocol over a deployed fibre. 

PMID- 24913130
TI  - A case series of 46 patients with lichen planopilaris: Demographics, clinical
      evaluation, and treatment experience.
AB  - BACKGROUND: Lichen planopilaris (LPP) is as a lymphocytic variant of primary
      cicatricial alopecia. OBJECTIVE: To evaluate the demographics, clinical findings,
      natural history, and response to various treatments of LPP. METHODS: A
      retrospective review of medical records of all patients with clinical and
      histopathological diagnoses of LPP. RESULTS: Out of 46 patients, there were 38
      (82.6%) women and 8 (17.4%) men. There was no clear association of specific
      medical background and medications with disease onset. The most frequent
      complaint was itching scalp. Asymptomatic hair loss was observed in 39.2%. LPP
      involved the entire scalp in 39.1%, vertex in 28.3%, anterior scalp and vertex in
      17.4%, fronto-temporal scalp in 6.5%, and posterior and parietal scalp in 6.5%.
      The topical treatment that caused the highest rate of symptomatic improvement was
      intralesional injection of corticosteroids. The treatment that led to the highest
      rate of remission was hydroxychloroquine combined with topical corticosteroid
      application. The remission rate was 6.5% after 3 months and 33% after 18 months.
      Of patients who achieved remission, 50% need continuous treatment to maintain
      remission. No patient had any visible hair regrowth on any treatment. CONCLUSION:
      The range of empiric topical and systemic treatments used gives unsatisfactory
      results, in LPP patients.

PMID- 24913131
TI  - Photodynamic therapy using a new formulation of 5-aminolevulinic acid for
      wrinkles in Asian skin: A randomized controlled split face study.
AB  - BACKGROUND: Photodynamic therapy (PDT) with intense pulsed light (IPL) was proven
      effective for photorejuvenation. Recently, a new formulation of 0.5% 5
      aminolevulinic acid (ALA) liposomal spray has been available. We designed a
      randomized split face study to evaluate usefulness and safety of IPL-PDT using a
      liposomal spray for periorbital wrinkles in Asians. METHODS: Patients received
      three treatments every 3 weeks. The half of the face was treated with IPL-PDT and
      the other half with long pulsed Nd:YAG laser (LPNY). Skin fluorescence was
      measured using a spectrophotometer for the guidance of PDT treatment. Wrinkle
      score was marked by two-blinded independent dermatologists. RESULTS: One patient
      dropped out due to 3-d lasting erythema on PDT side. The difference of mean
      reduction in lower and lateral periorbital wrinkle score on PDT side between the
      first and the last visit was statistically significant (p = 0.008 and p = 0.001,
      respectively). Lateral periorbital wrinkles treated with PDT showed better
      results than LPNY-treated sides. Twenty-five percent of patients reported good to
      excellent outcomes. CONCLUSION: This study demonstrated that PDT with a liposomal
      spray provided modest wrinkle reduction without serious adverse effect and it
      might be a promising treatment modality for wrinkle treatment in Asians.

PMID- 24913132
TI  - A case of multiple bone fractures due to the use of topical corticosteroid
      therapy for psoriasis.
AB  - A 45-year-old man who had psoriasis had applied topical clobetasol 17 propionate
      ointment on his whole body 2-3 times a week after the bath for 20 years. Physical
      examination showed abdominal distension, atrophy all over the skin, psoriatic
      plaques on the trunk, and extremities and multiple striae on the shoulders and
      legs. Morning plasma cortisol level and ACTH stimulation test confirmed the
      diagnosis of hypothalamic insufficiency. Bone mineral densitometry showed severe
      osteoporosis. Multiple bone fractures in the vertebrae and costa were detected on
      lumbar magnetic resonance imaging, the (99)Tc MDP whole-body bone scan, and
      thoracoabdominal computerized tomography imaging. Topical corticosteroid
      therapies have possible local and/or systemic side effects such as atrophy,
      telangiectasia, hypertricosis, and suppression of pituitary-adrenal axis. We
      present an interesting case with multiple bone fractures caused by long-time
      topical corticosteroid use. 

PMID- 24913133
TI  - Association of PTPN22+1858C/T polymorphism with Type 1 diabetes in the North
      Indian population.
AB  - A nonsynonymous SNP +1858C/T (rs2476601) in the protein tyrosine phosphatase,
      nonreceptor type 22(PTPN22) gene leading to Arg 620 Trp substitution is known to
      be associated with susceptibility to type 1 diabetes (T1D) and several other
      autoimmune diseases. We studied this polymorphism in 145 T1D patients and 210
      healthy controls from North India. The minor allele +1858T was observed to be
      significantly increased among patients as compared to healthy controls (2.76% vs
      0.5%, P = 0.027, OR = 5.93; 95% CI = 1.4-24.8). The association was also observed
      at the level of heterozygous C/T genotype (5.5% vs 0.95%, P = 0.026, OR = 6.07;
      95% CI = 1.43-25.6). The T allele and C/T genotype were predominantly found among
      patients who were positive for both glutamic acid decarboxylase 65 (GAD65) and
      insulin antigen 2 (IA2) autoantibodies and showed significantly increased
      frequencies (10%, P = 0.034, OR = 11.67; 95% CI = 1.58-84.1 and 20%, P = 0.031,
      OR = 13.0; 95% CI = 1.66-97.5, respectively) as compared to patients negative for
      these autoantibodies (0.95% and 1.9%, respectively). The results suggest that the
      PTPN22+1858T allele is positively associated with T1D in the North Indian
      population.

PMID- 24913134
TI  - Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in
      rabbit kittens.
AB  - BACKGROUND: Only one strain (the Czech CAPM-v351) of rabbit haemorrhagic disease
      virus (RHDV) has been released in Australia and New Zealand to control pest
      populations of the European rabbit O. cuniculus. Antigenic variants of RHDV known
      as RHDVa strains are reportedly replacing RHDV strains in other parts of the
      world, and Australia is currently investigating the usefulness of RHDVa to
      complement rabbit biocontrol efforts in Australia and New Zealand. RHDV
      efficiently kills adult rabbits but not rabbit kittens, which are more resistant
      to RHD the younger they are and which may carry the virus without signs of
      disease for prolonged periods. These different infection patterns in young
      rabbits may significantly influence RHDV epidemiology in the field and hence
      attempts to control rabbit numbers. METHODS: We quantified RHDV replication and
      shedding in 4-5 week old rabbits using quantitative real time PCR to assess their
      potential to shape RHDV epidemiology by shedding and transmitting virus. We
      further compared RHDV-v351 with an antigenic variant strain of RHDVa in kittens
      that is currently being considered as a potential RHDV strain for future release
      to improve rabbit biocontrol in Australia. RESULTS: Kittens were susceptible to
      infection with virus doses as low as 10 ID50. Virus growth, shedding and
      transmission after RHDVa infection was found to be comparable or non
      significantly lower compared to RHDV. Virus replication and shedding was observed
      in all kittens infected, but was low in comparison to adult rabbits. Both viruses
      were shed and transmitted to bystander rabbits. While blood titres indicated that
      4-5 week old kittens mostly clear the infection even in the absence of maternal
      antibodies, virus titres in liver, spleen and mesenteric lymph node were still
      high on day 5 post infection. CONCLUSIONS: Rabbit kittens are susceptible to
      infection with very low doses of RHDV, and can transmit virus before they
      seroconvert. They may therefore play an important role in RHDV field
      epidemiology, in particular for virus transmission within social groups during
      virus outbreaks.

PMID- 24913135
TI  - Extracellular matrix and cytochrome P450 gene expression can distinguish
      steatohepatitis from steatosis in mice.
AB  - One of the main questions regarding nonalcoholic fatty liver disease is the
      molecular background of the transition from simple steatosis (SS) to the
      inflammatory and fibrogenic condition of steatohepatitis (NASH). We examined the
      gene expression changes during progression from histologically normal liver to SS
      and NASH in models of obesity caused by hyperphagia or a high-fat diet.
      Microarray-based analysis revealed that the expression of 1445 and 264 probe sets
      was changed exclusively in SS and NASH samples, respectively, and 1577 probe sets
      were commonly altered in SS and NASH samples. Functional annotations indicated
      that transcriptome alterations that were common for NASH and SS, as well as
      exclusive for NASH, involved extracellular matrix (ECM)-related processes,
      although they differed in the type of matrix structure change. The expression of
      80 genes was significantly changed in all three comparisons: SS versus control,
      NASH versus control and NASH versus SS. Of these genes, epithelial membrane
      protein 1, IKBKB interacting protein and decorin were progressively up-regulated
      in both SS and NASH compared to normal tissue. The molecular context of
      interactions of encoded 80 proteins revealed that they are highly interconnected
      and significantly enriched for processes involving metabolism by cytochrome P450.
      Validation of 10 selected mRNAs encoding genes related to ECM and cytochrome P450
      with quantitative RT-PCR analysis showed consistent changes in their expression
      during NASH development. The expression profile of these genes has the potential
      to distinguish NASH from SS and normal tissue and may possibly be beneficial in
      the clinical diagnosis of NASH. 

PMID- 24913136
TI  - Disruption of brain white matter microstructure in women with anorexia nervosa.
AB  - BACKGROUND: The etiology of anorexia nervosa is still unknown. Multiple and
      distributed brain regions have been implicated in its pathophysiology, implying a
      dysfunction of connected neural circuits. Despite these findings, the role of
      white matter in anorexia nervosa has been rarely assessed. In this study, we used
      diffusion tensor imaging (DTI) to characterize alterations of white matter
      microstructure in a clinically homogeneous sample of patients with anorexia
      nervosa. METHODS: Women with anorexia nervosa (restricting subtype) and healthy
      controls underwent brain DTI. We used tract-based spatial statistics to compare
      fractional anisotropy (FA) and mean diffusivity (MD) maps between the groups.
      Furthermore, axial (AD) and radial diffusivity (RD) measures were extracted from
      regions showing group differences in either FA or MD. RESULTS: We enrolled 19
      women with anorexia nervosa and 19 healthy controls in our study. Patients with
      anorexia nervosa showed significant FA decreases in the parietal part of the left
      superior longitudinal fasciculus (SLF; p(FWE) < 0.05), with increased MD and RD
      but no differences in AD. Patients with anorexia nervosa also showed
      significantly increased MD in the fornix (p(FWE) < 0.05), accompanied by
      decreased FA and increased RD and AD. LIMITATIONS: Limitations include our modest
      sample size and cross-sectional design. CONCLUSION: Our findings support the
      presence of white matter pathology in patients with anorexia nervosa. Alterations
      in the SLF and fornix might be relevant to key symptoms of anorexia nervosa, such
      as body image distortion or impairments in body-energy-balance and reward
      processes. The differences found in both areas replicate those found in previous
      DTI studies and support a role for white matter pathology of specific neural
      circuits in individuals with anorexia nervosa.

PMID- 24913137
TI  - Do reward-processing deficits in schizophrenia-spectrum disorders promote
      cannabis use? An investigation of physiological response to natural rewards and
      drug cues.
AB  - BACKGROUND: Dysfunctional reward processing is present in individuals with
      schizophrenia-spectrum disorders (SSD) and may confer vulnerability to addiction.
      Our objective was to identify a deficit in patients with SSD on response to
      rewarding stimuli and determine whether this deficit predicts cannabis use.
      METHODS: We divided a group of patients with SSD and nonpsychotic controls into
      cannabis users and nonusers. Response to emotional and cannabis-associated visual
      stimuli was assessed using self-report, event-related potentials (using the late
      positive potential [LPP]), facial electromyography and skin-conductance response.
      RESULTS: Our sample comprised 35 patients with SSD and 35 nonpsychotic controls.
      Compared with controls, the patients with SSD showed blunted LPP response to
      pleasant stimuli (p = 0.003). Across measures, cannabis-using controls showed
      greater response to pleasant stimuli than to cannabis stimuli whereas cannabis
      using patients showed little bias toward pleasant stimuli. Reduced LPP response
      to pleasant stimuli was predictive of more frequent subsequent cannabis use (beta
      = -0.24, p = 0.034). LIMITATIONS: It is not clear if the deficit associated with
      cannabis use is specific to rewarding stimuli or nonspecific to any kind of
      emotionally salient stimuli. CONCLUSION: The LPP captures a reward-processing
      deficit in patients with SSD and shows potential as a biomarker for identifying
      patients at risk of heavy cannabis use.

PMID- 24913138
TI  - Accepting adoption's uncertainty: the limited ethics of pre-adoption genetic
      testing.
AB  - An increasing number of children are adopted in the United States from countries
      where both medical care and environmental conditions are extremely poor. In
      response to worries about the accuracy of medical histories, prospective adoptive
      parents increasingly request genetic testing of children prior to adoption.
      Though a general consensus on the ethics of pre-adoption genetic testing (PAGT)
      argues against permitting genetic testing on children available for adoption that
      is not also permitted for children in general, a view gaining traction argues for
      expanding the tests permitted. The reasoning behind this view is that the State
      has a duty to provide a child with parents who are the best "match," and thus all
      information that advances this end should be obtained. While the matching
      argument aims to promote the best interests of children, I show how it rests on
      the claim that what is in the best interests of children available for adoption
      is for prospective adoptive parents to have their genetic preferences satisfied
      such that the "genetics" of the children they end up adopting accurately reflects
      those preferences. Instead of protecting a vulnerable population, I conclude,
      PAGT contributes to the risks of harm such children face as it encourages people
      with strong genetic preferences to adopt children whose genetic backgrounds will
      always be uncertain. 

PMID- 24913140
TI  - The three-body problem.
AB  - The three-body problem, which describes three masses interacting through
      Newtonian gravity without any restrictions imposed on the initial positions and
      velocities of these masses, has attracted the attention of many scientists for
      more than 300 years. In this paper, we present a review of the three-body problem
      in the context of both historical and modern developments. We describe the
      general and restricted (circular and elliptic) three-body problems, different
      analytical and numerical methods of finding solutions, methods for performing
      stability analysis and searching for periodic orbits and resonances. We apply the
      results to some interesting problems of celestial mechanics. We also provide a
      brief presentation of the general and restricted relativistic three-body
      problems, and discuss their astronomical applications. 

PMID- 24913139
TI  - In vivo assessing of nanometric changes on the surface of whole tomatoes that
      have been inoculated with Candida guilliermondii yeast.
AB  - The cuticle of plants that covers the epidermis of cells, an interface between
      the fruit and the environment, has an important role to play in fruit quality
      because it prevents water loss and mechanical damage while simultaneously forming
      a barrier as it prevents phytopathogens from entering the fruit. All these
      factors give rise to flaws in the appearance of the fruit, thus contributing to
      marketing problems in the form of financial loss. In the search for solutions to
      some of these problems, certain biocontrolling yeasts have been introduced in the
      last few years. In the study described here, the changes observed on the surface
      of the whole tomato were evaluated in vivo during the first 72 h after
      inoculation by spraying Candida guilliermondii yeast onto the fruit's surface.
      The measurements were taken on a nanometric scale using atomic force microscopy;
      images were created in both contact and tapping modes. The results showed
      diminished roughness of the surface, which could contribute to reduced
      phytopathogen adherence due to the thinner contact area. These results
      furthermore showed that a yeast biofilm was formed on the fruit which probably
      helps to improve water retention inside the fruit.

PMID- 24913141
TI  - 119Sn Mossbauer spectroscopy study of the mechanism of lithium reaction with self
      organized Ti1/2Sn1/2O2 nanotubes.
AB  - Novel self-organized Ti1/2Sn1/2O2 nanotubes can be produced by the
      electrochemical anodization of co-sputtered Ti-Sn thin-films. Combined X-ray
      photoelectron spectroscopy and (119)Sn Mossbauer spectroscopy of pristine samples
      evidenced the octahedral substitution of Sn(4+) for Ti(4+) in the TiO2 structure.
      In addition to the improved lithium storage behaviour of the Ti1/2Sn1/2O2
      nanotubes, ex situ(119)Sn Mossbauer spectroscopy of cycled electrodes has
      sufficiently confirmed that no decomposition of the Ti1/2Sn1/2O2 structure
      occurred, and that no Li-Sn phase was formed during the discharge, corroborating
      that the electrochemical reaction is due exclusively to Li(+) insertion into the
      Ti1/2Sn1/2O2 nanotubes in the 1 <= U/V <= 2.6 voltage range.

PMID- 24913142
TI  - Effects of sleep loss on emotion recognition: a dissociation between face and
      word stimuli.
AB  - Short-term sleep deprivation, or extended wakefulness, adversely affects
      cognitive functions and behavior. However, scarce research has addressed the
      effects of sleep deprivation (SD) on emotional processing. In this study, we
      investigated the impact of reduced vigilance due to moderate sleep deprivation on
      the ability to recognize emotional expressions of faces and emotional content of
      words. Participants remained awake for 24 h and performed the tasks in two
      sessions, one in which they were not affected by sleep loss (baseline; BSL), and
      other affected by SD, according to a counterbalanced sequence. Tasks were carried
      out twice at 10:00 and 4:00 am, or at 12:00 and 6:00 am. In both tasks,
      participants had to respond to the emotional valence of the target stimulus:
      negative, positive, or neutral. The results showed that in the word task, sleep
      deprivation impaired recognition irrespective of the emotional valence of words.
      However, sleep deprivation impaired recognition of emotional face expressions
      mainly when they showed a neutral expression. Emotional face expressions were
      less affected by the sleep loss, but positive faces were more resistant than
      negative faces to the detrimental effect of sleep deprivation. The differential
      effects of sleep deprivation on recognition of the different emotional stimuli
      are indicative of emotional facial expressions being stronger emotional stimuli
      than emotional laden words. This dissociation may be attributed to the more
      automatic sensory encoding of emotional facial content.

PMID- 24913143
TI  - The broad-spectrum antiemetic effects ETI-385 result from stimulation of 5-HT1A
      and 5-HT1D receptors.
AB  - In the present study, we describe how a nonstoichiometric ratio of the isomers of
      8-hydroxy-2-(di-n-propylamino)tetralin (DPAT) produce a broad-spectrum of
      antiemetic effects in cats and shrews. Determination of the receptor profile of
      the isomers and testing them separately in cats revealed superior antiemetic
      effects but severe defensive behavior with the R isomer compared with the S
      isomer. Differing ratios yielded the best results with the 1:8 (R-S) ratio
      producing a drug more potent than DPAT and with negligible defensive behavior
      side effects. Studies with selective 5-HT1D ligands led to the conclusion that
      this site contributes antiemetic efficacy but is not related to defensive
      behavior, which is most likely a consequence of 5-HT7 receptor activation. ETI
      385 was effective in preventing emetic responses to provocative motion, drugs
      acting at the chemical trigger zone and cisplatin in both cats and shrews. The
      results support a clinical trial of this drug for antiemetic effects. 

PMID- 24913144
TI  - Hand movements with a phase structure and gestures that depict action stem from a
      left hemispheric system of conceptualization.
AB  - The present study addresses the previously discussed controversy on the
      contribution of the right and left cerebral hemispheres to the production and
      conceptualization of spontaneous hand movements and gestures. Although it has
      been shown that each hemisphere contains the ability to produce hand movements,
      results of left hemispherically lateralized motor functions challenge the view of
      a contralateral hand movement production system. To examine hemispheric
      specialization in hand movement and gesture production, ten right-handed
      participants were tachistoscopically presented pictures of everyday life actions.
      The participants were asked to demonstrate with their hands, but without speaking
      what they had seen on the drawing. Two independent blind raters evaluated the
      videotaped hand movements and gestures employing the Neuropsychological Gesture
      Coding System. The results showed that the overall frequency of right- and left
      hand movements is equal independent of stimulus lateralization. When hand
      movements were analyzed considering their Structure, the presentation of the
      action stimuli to the left hemisphere resulted in more hand movements with a
      phase structure than the presentation to the right hemisphere. Furthermore, the
      presentation to the left hemisphere resulted in more right and left-hand
      movements with a phase structure, whereas the presentation to the right
      hemisphere only increased contralateral left-hand movements with a phase
      structure as compared to hand movements without a phase structure. Gestures that
      depict action were primarily displayed in response to stimuli presented in the
      right visual field than in the left one. The present study shows that both
      hemispheres possess the faculty to produce hand movements in response to action
      stimuli. However, the left hemisphere dominates the production of hand movements
      with a phase structure and gestures that depict action. We therefore conclude
      that hand movements with a phase structure and gestures that represent action
      stem from a left hemispheric system of conceptualization.

PMID- 24913146
TI  - Prediction of prone-to-supine tumor displacement in the breast using patient
      position change: investigation with prone MRI and supine CT.
AB  - BACKGROUND: One of the challenges for clinical use of preoperative breast
      magnetic resonance imaging (MRI) is how to transfer prone MRI information to the
      operating theater with a supine surgical position. The aim of this study was to
      retrospectively evaluate tumor displacement in the breast by changing the patient
      position from prone to supine (prone-to-supine tumor displacement), using
      preoperative prone MRI and supine computed tomography (CT). METHODS:
      Preoperatively, 55 Japanese women with 57 breast cancer lesions underwent breast
      MRI in the prone position and breast CT in the supine position. Tumor positions
      in both the prone and supine positions were measured on X-, Y-, and Z-coordinates
      by fixing the nipple to the origin (0, 0, 0). As an indicator of the mobility of
      the breast, the ratio of the breast projection between the prone MRI and supine
      CT (prone-to-supine projection ratio) was calculated. The direction and distance
      of prone-to-supine tumor displacement was analyzed by dividing the breast into
      four quadrants according to the tumor position. RESULTS: When changing the
      patient position from prone to supine, tumors located in the inner-upper and
      inner-lower quadrants tended to move radially toward the center of the nipple.
      The movement distance of the tumors in the inner-lower and outer-lower quadrants
      was very strongly correlated with the prone-to-supine breast projection ratio (r
      >= 0.8, p < 0.05). Conversely, in the outer-upper quadrant, the direction of
      tumor displacement was variable, and the distance of tumor displacement did not
      correlate with the prone-to-supine projection ratio. CONCLUSIONS: The present
      study showed that prone-to-supine tumor displacement in the breast differs
      depending on tumor location. The inner-lower quadrant of the breast may be the
      most predictable area for prone-to-supine tumor displacement.

PMID- 24913145
TI  - A highly recurrent RPS27 5'UTR mutation in melanoma.
AB  - The incidence of melanoma continues to rise globally and is increasing at a rate
      greater than any other cancer. To systematically search for new genes involved in
      melanomagenesis, we collated exome sequencing data from independent melanoma
      cohort datasets, including those in the public domain. We identified recurrent
      mutations that may drive melanoma growth, survival or metastasis, and which may
      hold promise for the design of novel therapies to treat melanoma. These included
      a frequent recurrent (i.e. hotspot) mutation in the 5' untranslated region of
      RPS27 in ~10% of samples. We show that the mutation expands the 5'TOP element, a
      motif known to regulate the expression of most of the ribosomal protein family,
      to which RPS27 belongs, and thus might sensitize the mutated transcript to growth
      mediated regulation. This finding highlights not only the important role of non
      protein coding genetic aberrations in cancer development but also their potential
      as novel therapeutic targets. 

PMID- 24913147
TI  - Offenders' risk-taking attitude inside and outside the prison walls.
AB  - It has long been assumed that risk taking is closely associated with criminal
      behavior. One reason for placing criminals behind bars--aside from punishment and
      protecting the public--is to prevent them from engaging in further risky criminal
      activities. Limited attention has been paid to whether being inside or outside
      prison affects offenders' risk-taking behaviors and attitudes. We compared risk
      taking behaviors and attitudes in five risk domains (ethical, financial,
      health/safety, recreational, social) among 75 incarcerated offenders (i.e.,
      offenders who are currently in prison) and 45 ex-offenders (i.e., offenders who
      have just been released from prison). Ex-offenders reported higher likelihood of
      engaging in risky behavior, driven largely by a willingness to take more risks in
      the recreational and ethical domains. Benefits attributed to risk taking as well
      as risk perception did not differ between incarcerated and ex-offenders,
      indicating that the opportunity to take risks might underlie behavioral risk
      intentions. Our results also indicate that risk-taking activities are better
      predicted by the expected benefits rather than by risk perception, aside from the
      health/safety domain. These results highlight the importance of studying the
      person and the environment and examining risk taking in a number of content
      domains.

PMID- 24913148
TI  - Development of Measures to Assess Personal Recovery in Young People Treated in
      Specialist Mental Health Services.
AB  - BACKGROUND: Recovery has become a central concept in mental health service
      delivery, and several recovery-focused measures exist for adults. The concept's
      applicability to young people's mental health experience has been neglected, and
      no measures yet exist. Aim The aim of this work is to develop measures of
      recovery for use in specialist child and adolescent mental health services.
      METHOD: On the basis of 21 semi-structured interviews, three recovery measures
      were devised, one for completion by the young person and two for completion by
      the parent/carer. Two parent/carer measures were devised in order to assess both
      their perspective on their child's recovery and their own recovery process. The
      questionnaires were administered to a UK sample of 47 young people (10-18 years
      old) with anxiety and depression and their parents, along with a measure used to
      routinely assess treatment progress and outcome and a measure of self-esteem.
      RESULTS: All three measures had high internal consistency (alpha >= 0.89). Young
      people's recovery scores were correlated negatively with scores on a measure used
      to routinely assess treatment progress and outcome (r = -0.75) and positively
      with self-esteem (r = 0.84). Parent and young persons' reports of the young
      person's recovery were positively correlated (r = 0.61). Parent report of the
      young person's recovery and of their own recovery process were positively
      correlated (r = 0.75). CONCLUSION: The three measures have the potential to be
      used in mental health services to assess recovery processes in young people with
      mental health difficulties and correspondence with symptomatic improvement. The
      measures provide a novel way of capturing the parental/caregiver perspective on
      recovery and caregivers' own wellbeing. KEY PRACTITIONER MESSAGE: No tools exist
      to evaluate recovery-relevant processes in young people treated in specialist
      mental health services. This study reports on the development and psychometric
      evaluation of three self-report recovery-relevant assessments for young people
      and their caregivers. Findings indicate a high degree of correspondence between
      young person and caregiver reports of recovery in the former. The recovery
      assessments correlate inversely with a standardized symptom-focused measure and
      positively with self-esteem.

PMID- 24913149
TI  - Downregulation of Sirt1 as aging change in advanced heart failure.
AB  - BACKGROUND: In congestive heart failure the balance between cell death and cell
      survival in cardiomyocytes is compromised. Sirtuin 1 (Sirt1) activates cell
      survival machinery and has been shown to be protective against
      ischemia/reperfusion injury in murine heart. The role of Sirt1 in heart failure,
      especially in human hearts is not clear. RESULTS: The expression of Sirt1 and
      other (associated) downstream molecules in human cardiomyocytes from patients
      with advanced heart failure was examined. Sirt1 was down-regulated (54.92% +/-
      7.80% in advanced heart failure samples compared with healthy control
      cardiomyocytes). The modulation of molecules involved in cardiomyocyte survival
      and death in advanced heart failure were also examined. The expression of Mn
      superoxide dismutase and thioredoxin1, as well as an antiapoptotic molecule, Bcl
      xL, were all significantly reduced in advanced heart failure cardiomyoctes (0.71
      +/- 0.02-fold, 0.61 +/- 0.05-fold, and 0.53 +/- 0.08-fold vs. control,
      respectively); whereas the expression of proapoptotic molecule Bax was
      significantly increased (1.62 +/- 0.18-fold vs. control). Increased TUNEL
      positive number of cardiomyocytes and oxidative stress, confirmed by 8
      hydorxydeoxyguanosine staining, were associated with advanced heart failure. The
      AMPK-Nampt-Sirt1 axis also showed inhibition in advanced heart failure in
      addition to severely impaired AMPK activation. Increased p53 (acetyl form) and
      decreased FoxO1 translocation in the nucleus may be the mechanism of down
      regulation of antioxidants and up-regulation of proapoptotic molecules due to low
      expression of Sirt1. CONCLUSION: In advanced heart failure, low Sirt1 expression,
      like aging change may be a significant contributing factor in the downregulation
      of antioxidants and upregulation of proapoptotic molecules through the p53,
      FoxO1, and oxidative stress pathways.

PMID- 24913150
TI  - Geographic variations in access and utilization of cancer screening services:
      examining disparities among American Indian and Alaska Native Elders.
AB  - BACKGROUND: Despite recommendations for cancer screening for breast and
      colorectal cancer among the Medicare population, preventive screenings rates are
      often lower among vulnerable populations such as the small but rapidly growing
      older American Indian and Alaska Native (AIAN) population. This study seeks to
      identify potential disparities in the availability of screening services,
      distance to care, and the utilization of cancer screening services for Medicare
      beneficiaries residing in areas with a higher concentration of AIAN populations.
      METHODS: Using the county (n =3,225) as the level of analysis, we conducted a
      cross-sectional analysis of RTI International's Spatial Impact Factor Data (2012)
      to determine the level of disparities for AIAN individuals. The outcomes of
      interest include: the presence of health care facilities in the county, the
      average distance in miles to the closest provider of mammography and colonoscopy
      (analyzed separately) and utilization of screening services (percent of adults
      aged 65 and older screened by county). RESULTS: Counties with higher
      concentrations of AIAN individuals had greater disparities in access and
      utilization of cancer screening services. Even after adjusting for income,
      education, state of residence, population 65 and older and rurality, areas with
      higher levels of AIAN individuals were more likely to see disparities with regard
      to health care services related to mammograms (p <= .05; longer distance, lower
      screening) and colonoscopies (p <= .05; longer distance, lower screening).
      CONCLUSIONS: These findings provide evidence of a gap in service availability,
      utilization and access facing areas with higher levels of AIAN individuals
      throughout the US. Without adequate resources in place, these areas will continue
      to have less access to services and poorer health which will be accelerated as
      the population of older adults grows.

PMID- 24913151
TI  - Proton beam therapy reduces the incidence of acute haematological and
      gastrointestinal toxicities associated with craniospinal irradiation in pediatric
      brain tumors.
AB  - BACKGROUND: The benefits of proton beam craniospinal irradiation (PrBCSI) in
      children have been extensively reported in dosimetric studies. However, there is
      limited clinical evidence supporting the use of PrBCSI. We compared the acute
      toxicity of PrBCSI relative to that of conventional photon beam CSI (PhBCSI) in
      children with brain tumours. MATERIAL AND METHODS: We prospectively evaluated the
      haematological and gastrointestinal toxicities in 30 patients who underwent
      PrBCSI between April 2008 and December 2012. As a reference group, we
      retrospectively evaluated the medical records of 13 patients who underwent PhBCSI
      between April 2003 and April 2012. The median follow-up time from starting CSI
      was 22 months (range 2-118 months). The mean irradiation dose was 32.1 Gy (range
      23.4-39.6 Gy) and 29.4 CGE (cobalt grey equivalents; range 19.8-39.6), in the
      PrBCSI and PhBCSI groups, respectively (p = 0.236). RESULTS: There was no
      craniospinal fluid space relapse after curative therapy in either group of
      patients. Thrombocytopenia was less severe in the PrBCSI group than in the PhBCSI
      group (p = 0.012). The recovery rates of leukocyte and platelet counts measured
      one month after treatment were significantly greater in the PrBCSI group than in
      the PhBCSI group (p = 0.003 and p = 0.010, respectively). Diarrhoea was reported
      by 23% of patients in the PhBCSI group versus none in the PrBCSI group (p =
      0.023). CONCLUSIONS: The incidence rates of thrombocytopenia and diarrhoea were
      lower in the PrBCSI group than in the PhBCSI group. One month after completing
      treatment, the recovery from leukopenia and thrombocytopenia was better in
      patients treated with PrBCSI than in those treated with PhBCSI.

PMID- 24913152
TI  - Eosinophilia in routine blood samples as a biomarker for solid tumor development 
      A study based on the Copenhagen Primary Care Differential Count (CopDiff)
      Database.
AB  - BACKGROUND: Eosinophilia may represent an early paraclinical sign of malignant
      disease and a host anti-tumor effect. The association between eosinophilia and
      the development of solid tumors has never before been examined in an
      epidemiological setting. The aim of the present study was to investigate
      eosinophilia in routine blood samples as a potential biomarker of solid tumor
      development in a prospective design. MATERIAL AND METHODS: From the Copenhagen
      Primary Care Differential Count (CopDiff) Database, we identified 356 196
      individuals with at least one differential cell count (DIFF) encompassing the
      eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and
      categorized according to no (< 0.5 * 10(9)/l), mild (>= 0.5-1.0 * 10(9)/l) or
      severe (>= 1.0 * 10(9)/l) eosinophilia. From the Danish Civil Registration System
      and the Danish Cancer Registry we ascertained all-cause death and solid tumors
      within the first three years following the DIFF. Using multivariable logistic
      regression, odds ratios (OR) were calculated and adjusted for previous
      eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and
      Charlson's Comorbidity Index. RESULTS: The risk of bladder cancer was increased
      with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with
      eosinophilia were observed for the remaining solid cancers. CONCLUSION: We
      demonstrate that eosinophilia in routine blood samples associates with an
      increased risk of bladder cancer. Our data emphasize that additional preclinical
      studies are needed in order to shed further light on the role of eosinophils in
      carcinogenesis, where it is still unknown whether the cells contribute to tumor
      immune surveillance or neoplastic evolution.

PMID- 24913153
TI  - Treatment outcome in T-cell lymphoblastic lymphoma in adults - a population-based
      study from the Swedish Lymphoma Registry.
AB  - BACKGROUND: T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor
      lymphoblast origin, for which there is no standard treatment for adults. Results
      of current treatment strategies in selected populations do exist but are largely
      unreported for unselected series. Here, we aimed to investigate treatment outcome
      in a population-based cohort. MATERIAL AND METHODS: Patients were identified
      through the Swedish Lymphoma Registry and data was retrospectively collected for
      all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009.
      RESULTS: A total of 39 patients with median age 40 years (range 18-78) were
      identified with females being significantly older than males (median age 66 vs.
      37, p = 0.027). The five-year overall survival for all patients was 42%. Female
      gender was associated with shorter survival also when adjusted for treatment
      strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received
      intensive chemotherapy, otherwise used for treatment of acute lymphoblastic
      leukemia (ALL), which resulted in an overall response rate of 97% and a five-year
      progression-free survival (PFS) of 49%. In this group only CNS involvement at
      diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with
      hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to
      progression compared to patients receiving only chemotherapy (p = 0.047). The
      major reason for treatment failure was relapse and in this series 18-fluoro
      deoxyglucose positron emission tomography (PET) did not predict this risk.
      CONCLUSION: This population-based study indicates that all fit T-LBL patients
      should be considered for intensive treatment. Our results also suggest a
      beneficial effect of mediastinal irradiation in combination with hyper-CVAD
      treatment. Relapsing patients have a dismal outcome irrespective of salvage
      treatment.

PMID- 24913154
TI  - Improved survival among older acute myeloid leukemia patients - a population
      based study.
AB  - BACKGROUND: Survival in acute myeloid leukemia (AML) has improved in younger
      patients over the last decade. This study was conducted to evaluate the relative
      survival rates in older AML patients over two decades in the US. MATERIAL AND
      METHODS: We analyzed Surveillance, Epidemiology, and End Results (SEER) registry
      database to evaluate relative survival rate in older (>= 75 years) AML population
      diagnosed during 1992-2009. We selected AML patients from 13 registries of SEER
      18 database to compare RS during 1992-2000 and 2001-2009. RESULTS: The relative
      survival rates improved significantly during 2001-2009 compared to 1992-2000 for
      all age groups and sex. For young elderly patients (75-84 years) RS increased
      from 13.1 +/- 0.8% to 17.4 +/- 0.9% at one year Z-value = 3.98, p < 0.0001 and
      from 2.0 +/- 0.4 to 2.6 +/- 0.5%, Z-value = 3.61, p < 0.0005 at five years.
      Similarly, for very elderly (>= 85 years) patients RS increased from 5.3 +/- 1.0%
      to 8.0 +/- 1.0%, Z-value = 3.03, p < 0.005 at one year, but no improvement seen
      at five years. CONCLUSION: The relative survival in elderly AML has increased
      significantly during 2001-2009 compared to 1992-2000.

PMID- 24913155
TI  - Homeopathy for allergic rhinitis: protocol for a systematic review.
AB  - BACKGROUND: Allergic rhinitis is a global health problem that is often treated
      with homeopathy. The objective of this review will be to evaluate the
      effectiveness of homeopathic treatment of allergic rhinitis. METHODS/DESIGN: The
      authors will conduct a systematic review. We will search Medline, CENTRAL,
      CINAHL, EMBASE, AMED, CAM-Quest, Google Scholar and reference lists of identified
      studies up to December 2013.The review will include randomized controlled trials
      that evaluate homeopathic treatment of allergic rhinitis. Studies with
      participants of all ages, with acute or chronic comorbidities will be included.
      Patients with immunodeficiency will not be included. The diagnosis will be based
      on the published guidelines of diagnosis and classification. Studies of all
      homeopathy modalities (clinical, complex and classical homeopathy, and isopathy)
      will be included. We will include trials with both active controls (conventional
      therapy, standard care) and placebo controls.The primary outcomes are: an
      improvement of global symptoms recorded in validated daily or weekly diaries and
      any scores from validated visual analogue scales; the total Quality of Life Score
      (such as the Juniper RQLQ);individual symptoms scores which include any
      appropriate measures of nasal obstruction, runny nose, sneezing, itching, and eye
      symptoms; and number of days requiring medication. Secondary outcomes selected
      will include serum immunoglobin E (IgE) levels, individual ocular symptoms,
      adverse events, and the use of rescue medication.Treatment effects will be
      measured by calculating the mean difference and the standardized mean difference
      with 95% confidence interval (CI) for continuous data. Risk ratio or, if
      feasible, odds ratio will be calculated with 95% CI for dichotomous data. After
      assessing clinical and statistical heterogeneity, meta-analysis will be
      performed, if appropriate. The individual participant will be the unit of
      analysis. Descriptive information on missing data will be included about
      participants missing due to drop out, whether there was intention to treat or per
      protocol analysis and missing statistics. A number of subgroups, homeopathic
      potency, age groups, and types of allergic rhinitis (seasonal or perennial) will
      be analyzed. Sensitivity analysis will be performed to explore the impact of risk
      of bias on overall treatment effect. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42013006741.

PMID- 24913156
TI  - Efficacy of repeated intravenous administration of peramivir against highly
      pathogenic avian influenza A (H5N1) virus in cynomolgus macaques.
AB  - Highly pathogenic avian influenza A (H5N1) viruses cause severe and often fatal
      disease in humans. We evaluated the efficacy of repeated intravenous dosing of
      the neuraminidase inhibitor peramivir against highly pathogenic avian influenza
      virus A/Vietnam/UT3040/2004 (H5N1) infection in cynomolgus macaques. Repeated
      dosing of peramivir (30 mg/kg/day once a day for 5 days) starting immediately
      after infection significantly reduced viral titers in the upper respiratory
      tract, body weight loss, and cytokine production and resulted in a significant
      body temperature reduction in infected macaques compared with that of macaques
      administered a vehicle (P < 0.05). Repeated administration of peramivir starting
      at 24 h after infection also resulted in a reduction in viral titers and a
      reduction in the period of virus detection in the upper respiratory tract,
      although the body temperature change was not statistically significant. The
      macaque model used in the present study demonstrated that inhibition of viral
      replication at an early time point after infection by repeated intravenous
      treatment with peramivir is critical for reduction of the production of
      cytokines, i.e., interleukin-6 (IL-6), tumor necrosis factor alpha, gamma
      interferon, monocyte chemotactic protein 1, and IL-12p40, resulting in
      amelioration of symptoms caused by highly pathogenic avian influenza virus
      infection. 

PMID- 24913157
TI  - Multidisciplinary analysis of a nontoxigenic Clostridium difficile strain with
      stable resistance to metronidazole.
AB  - Stable resistance to metronidazole in a nontoxigenic Clostridium difficile strain
      was investigated at both the genomic and proteomic levels. Alterations in the
      metabolic pathway involving the pyruvate-ferredoxin oxidoreductase were found,
      suggesting that reduction of metronidazole, required for its activity, may be
      less efficient in this strain. Proteomic studies also showed a cellular response
      to oxidative stress. 

PMID- 24913158
TI  - His224 alters the R2 drug binding site and Phe218 influences the catalytic
      efficiency of the metallo-beta-lactamase VIM-7.
AB  - Metallo-beta-lactamases (MBLs) are the causative mechanism for resistance to beta
      lactams, including carbapenems, in many Gram-negative pathogenic bacteria. One
      important family of MBLs is the Verona integron-encoded MBLs (VIM). In this
      study, the importance of residues Asp120, Phe218, and His224 in the most
      divergent VIM variant, VIM-7, was investigated to better understand the roles of
      these residues in VIM enzymes through mutations, enzyme kinetics, crystal
      structures, thermostability, and docking experiments. The tVIM-7-D120A mutant
      with a tobacco etch virus (TEV) cleavage site was enzymatically inactive, and its
      structure showed the presence of only the Zn1 ion. The mutant was less
      thermostable, with a melting temperature (T(m)) of 48.5 degrees C, compared to
      55.3  degrees C for the wild-type tVIM-7. In the F218Y mutant, a hydrogen bonding
      cluster was established involving residues Asn70, Asp84, and Arg121. The tVIM-7
      F218Y mutant had enhanced activity compared to wild-type tVIM-7, and a slightly
      higher Tm (57.1  degrees C) was observed, most likely due to the hydrogen bonding
      cluster. Furthermore, the introduction of two additional hydrogen bonds adjacent
      to the active site in the tVIM-7-H224Y mutant gave a higher thermostability
      (T(m), 62.9  degrees C) and increased enzymatic activity compared to those of the
      wild-type tVIM-7. Docking of ceftazidime in to the active site of tVIM-7, tVIM-7
      H224Y, and VIM-7-F218Y revealed that the side-chain conformations of residue 224
      and Arg228 in the L3 loop and Tyr67 in the L1 loop all influence possible
      substrate binding conformations. In conclusion, the residue composition of the L3
      loop, as shown with the single H224Y mutation, is important for activity
      particularly toward the positively charged cephalosporins like cefepime and
      ceftazidime.

PMID- 24913159
TI  - SAMHD1 specifically affects the antiviral potency of thymidine analog HIV reverse
      transcriptase inhibitors.
AB  - Sterile alpha motif and histidine-aspartic domain-containing protein 1 (SAMHD1)
      is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase recently recognized
      as an antiviral factor that acts by depleting dNTP availability for viral reverse
      transcriptase (RT). SAMHD1 restriction is counteracted by the human
      immunodeficiency virus type 2 (HIV-2) accessory protein Vpx, which targets SAMHD1
      for proteosomal degradation, resulting in an increased availability of dNTPs and
      consequently enhanced viral replication. Nucleoside reverse transcriptase
      inhibitors (NRTI), one of the most common agents used in antiretroviral therapy,
      compete with intracellular dNTPs as the substrate for viral RT. Consequently,
      SAMHD1 activity may be influencing NRTI efficacy in inhibiting viral replication.
      Here, a panel of different RT inhibitors was analyzed for their different
      antiviral efficacy depending on SAMHD1. Antiviral potency was measured for all
      the inhibitors in transformed cell lines and primary monocyte-derived macrophages
      and CD4(+) T cells infected with HIV-1 with or without Vpx. No changes in
      sensitivity to non-NRTI or the integrase inhibitor raltegravir were observed, but
      for NRTI, sensitivity significantly changed only in the case of the thymidine
      analogs (AZT and d4T). The addition of exogenous thymidine mimicked the change in
      viral sensitivity observed after Vpx-mediated SAMHD1 degradation, pointing toward
      a differential effect of SAMHD1 activity on thymidine. Accordingly, sensitivity
      to AZT was also reduced in CD4(+) T cells infected with HIV-2 compared to
      infection with the HIV-2DeltaVpx strain. In conclusion, reduction of SAMHD1
      levels significantly decreases HIV sensitivity to thymidine but not other
      nucleotide RT analog inhibitors in both macrophages and lymphocytes. 

PMID- 24913160
TI  - Safety and pharmacokinetics of XOMA 3AB, a novel mixture of three monoclonal
      antibodies against botulinum toxin A.
AB  - Botulinum neurotoxin A is a category A bioterrorism agent. Current antitoxin
      therapies are scarce and produce adverse reactions. XOMA 3AB consists of 3 IgG1
      monoclonal antibodies (MAbs), each with a distinct human or humanized variable
      region, which bind to distinct epitopes on botulinum neurotoxin serotype A. This
      first-in-human study evaluated the safety and pharmacokinetics (PK) of escalating
      doses of XOMA 3AB administered intravenously (i.v.) to healthy adults. In this
      double-blind placebo-controlled dose escalation study, 3 cohorts of 8 healthy
      subjects received a single intravenous dose of XOMA 3AB or placebo at a 3:1
      ratio. Follow-up examinations included physical examinations, hematology and
      chemistry blood tests, electrocardiograms, and pharmacokinetics. Pharmacokinetic
      parameters were estimated using noncompartmental methods. There were no infusion
      discontinuations or hypersensitivity reactions. Two or more subjects experienced
      headache, hyperglycemia, or anemia; none was dose related. All adverse events
      (AEs) were mild to moderate except for an episode of exercise-induced elevation
      of a subject's creatine phosphokinase (CPK) level, unrelated to XOMA 3AB.
      Concentration-time plots demonstrated a peak in MAb concentrations 1 to 2 h after
      completion of the infusion, after which the levels declined in a biexponential
      decay pattern for all analytes. For each MAb, the maximum concentration of drug
      in serum (Cmax) and the area under the concentration-time curve from 0 to
      infinity (AUCinf) increased as the dose increased. Clearance of the humanized
      mouse MAb was more rapid than that of the two fully human MAbs, particularly at
      the lowest dose. None of the MAbs was immunogenic. At the doses administered,
      XOMA 3AB was well tolerated. These safety findings support further investigation
      of XOMA 3AB as a potential agent for botulism treatment and postexposure
      prophylaxis. (This study has been registered at ClinicalTrials.gov under
      registration no. NCT01357213.). 

PMID- 24913161
TI  - Population pharmacokinetic analysis of voriconazole and anidulafungin in adult
      patients with invasive aspergillosis.
AB  - To assess the pharmacokinetics (PK) of voriconazole and anidulafungin in patients
      with invasive aspergillosis (IA) in comparison with other populations, sparse PK
      data were obtained for 305 adults from a prospective phase 3 study comparing
      voriconazole and anidulafungin in combination versus voriconazole monotherapy
      (voriconazole, 6 mg/kg intravenously [IV] every 12 h [q12h] for 24 h followed by
      4 mg/kg IV q12h, switched to 300 mg orally q12h as appropriate; with placebo or
      anidulafungin IV, a 200-mg loading dose followed by 100 mg q24h). Voriconazole PK
      was described by a two-compartment model with first-order absorption and mixed
      linear and time-dependent nonlinear (Michaelis-Menten) elimination; anidulafungin
      PK was described by a two-compartment model with first-order elimination. For
      voriconazole, the normal inverse Wishart prior approach was implemented to
      stabilize the model. Compared to previous models, no new covariates were
      identified for voriconazole or anidulafungin. PK parameter estimates of
      voriconazole and anidulafungin are in agreement with those reported previously
      except for voriconazole clearance (the nonlinear clearance component became
      minimal). At a 4-mg/kg IV dose, voriconazole exposure tended to increase slightly
      as age, weight, or body mass index increased, but the difference was not
      considered clinically relevant. Estimated voriconazole exposures in IA patients
      at 4 mg/kg IV were higher than those reported for healthy adults (e.g., the
      average area under the curve over a 12-hour dosing interval [AUC0-12] at steady
      state was 46% higher); while it is not definitive, age and concomitant
      medications may impact this difference. Estimated anidulafungin exposures in IA
      patients were comparable to those reported for the general patient population.
      This study was approved by the appropriate institutional review boards or ethics
      committees and registered on ClinicalTrials.gov (NCT00531479). 

PMID- 24913162
TI  - Treatment of murine cerebral malaria by artemisone in combination with
      conventional antimalarial drugs: antiplasmodial effects and immune responses.
AB  - The decreasing effectiveness of antimalarial therapy due to drug resistance
      necessitates constant efforts to develop new drugs. Artemisinin derivatives are
      the most recent drugs that have been introduced and are considered the first line
      of treatment, but there are already indications of Plasmodium falciparum
      resistance to artemisinins. Consequently, drug combinations are recommended for
      prevention of the induction of resistance. The research here demonstrates the
      effects of novel combinations of the new artemisinin derivative, artemisone, a
      recently described 10-alkylamino artemisinin derivative with improved
      antimalarial activity and reduced neurotoxicity. We here investigate its ability
      to kill P. falciparum in a high-throughput in vitro assay and to protect mice
      against lethal cerebral malaria caused by Plasmodium berghei ANKA when used alone
      or in combination with established antimalarial drugs. Artemisone effects against
      P. falciparum in vitro were synergistic with halofantrine and mefloquine, and
      additive with 25 other drugs, including chloroquine and doxycycline. The
      concentrations of artemisone combinations that were toxic against THP-1 cells in
      vitro were much higher than their effective antimalarial concentration.
      Artemisone, mefloquine, chloroquine, or piperaquine given individually mostly
      protected mice against cerebral malaria caused by P. berghei ANKA but did not
      prevent parasite recrudescence. Combinations of artemisone with any of the other
      three drugs did completely cure most mice of malaria. The combination of
      artemisone and chloroquine decreased the ratio of proinflammatory (gamma
      interferon, tumor necrosis factor) to anti-inflammatory (interleukin 10 [IL-10],
      IL-4) cytokines in the plasma of P. berghei-infected mice. Thus, artemisone in
      combinations with other antimalarial drugs might have a dual action, both killing
      parasites and limiting the potentially deleterious host inflammatory response. 

PMID- 24913164
TI  - Emergence of VIM-2 and IMP-15 carbapenemases and inactivation of oprD gene in
      carbapenem-resistant Pseudomonas aeruginosa clinical isolates from Lebanon.
AB  - We report here the emergence of VIM-2 and IMP-15 carbapenemases in a series of
      clinical isolates of carbapenem-resistant Pseudomonas aeruginosa in Lebanon. We
      also describe the disruption of the oprD gene by either mutations or insertion
      sequence (IS) elements ISPa1328 and ISPre2 isoform. Our study reemphasizes a
      rapid dissemination of the VIM-2 carbapenemase-encoding gene in clinical isolates
      of P. aeruginosa in the Mediterranean basin. 

PMID- 24913163
TI  - Scalable preparation and differential pharmacologic and toxicologic profiles of
      primaquine enantiomers.
AB  - Hematotoxicity in individuals genetically deficient in glucose-6-phosphate
      dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the
      only antimalarial drug in clinical use for treatment of relapsing Plasmodium
      vivax malaria. PQ is currently clinically used in its racemic form. A scalable
      procedure was developed to resolve racemic PQ, thus providing pure enantiomers
      for the first time for detailed preclinical evaluation and potentially for
      clinical use. These enantiomers were compared for antiparasitic activity using
      several mouse models and also for general and hematological toxicities in mice
      and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity
      than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ
      was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of
      Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed
      more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more
      methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3
      days, while (-)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic
      anemia associated with human G6PD deficiency, it was also demonstrated that (-)
      (R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells
      engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ
      shows greater potency in terms of antiparasitic efficacy in rodents, it is also
      more hematotoxic than (-)-(R)-PQ in mice and dogs. Activity and toxicity
      differences of PQ enantiomers in different species can be attributed to their
      different pharmacokinetic and metabolic profiles. Taken together, these studies
      suggest that (-)-(R)-PQ may have a better safety margin than the racemate in
      human. 

PMID- 24913165
TI  - Population structure of KPC-producing Klebsiella pneumoniae isolates from
      midwestern U.S. hospitals.
AB  - Genome sequencing of carbapenem-resistant Klebsiella pneumoniae isolates from
      regional U.S. hospitals was used to characterize strain diversity and the
      bla(KPC) genetic context. A phylogeny based on core single-nucleotide variants
      (SNVs) supports a division of sequence type 258 (ST258) into two distinct groups.
      The primary differences between the groups are in the capsular polysaccharide
      locus (cps) and their plasmid contents. A strict association between clade and
      KPC variant was found. The bla(KPC) gene was found on variants of two plasmid
      backbones. This study indicates that highly similar K. pneumoniae subpopulations
      coexist within the same hospitals over time.

PMID- 24913166
TI  - Differential protection from tobramycin by extracellular polymeric substances
      from Acinetobacter baumannii and Staphylococcus aureus biofilms.
AB  - We investigated biofilms of two pathogens, Acinetobacter baumannii and
      Staphylococcus aureus, to characterize mechanisms by which the extracellular
      polymeric substance (EPS) found in biofilms can protect bacteria against
      tobramycin exposure. To do so, it is critical to study EPS-antibiotic
      interactions in a homogeneous environment without mass transfer limitations.
      Consequently, we developed a method to grow biofilms, harvest EPS, and then
      augment planktonic cultures with isolated EPS and tobramycin. We demonstrated
      that planktonic cultures respond differently to being treated with different
      types of EPS (A. baumannii versus S. aureus) in the presence of tobramycin. By
      harvesting EPS from the biofilms, we found that A. baumannii EPS acts as a
      "universal protector" by inhibiting tobramycin activity against bacterial cells
      regardless of species; S. aureus EPS did not show any protective ability in cell
      cultures. Adding Mg(2+) or Ca(2+) reduced the protective effect of A. baumannii
      EPS. Finally, when we selectively digested the proteins or DNA of the EPS, we
      found that the protective ability did not change, suggesting that neither has a
      significant role in protection. To the best of our knowledge, this is the first
      study that demonstrates how EPS protects pathogens against antibiotics in a
      homogeneous system without mass transfer limitations. Our results suggest that
      EPS protects biofilm communities, in part, by adsorbing antibiotics near the
      surface. This may limit antibiotic diffusion to the bottom of the biofilms but is
      not likely to be the only mechanism of protection. 

PMID- 24913167
TI  - Fatty acid synthesis and pyruvate metabolism pathways remain active in
      dihydroartemisinin-induced dormant ring stages of Plasmodium falciparum.
AB  - Artemisinin (ART)-based combination therapy (ACT) is used as the first-line
      treatment of uncomplicated falciparum malaria worldwide. However, despite high
      potency and rapid action, there is a high rate of recrudescence associated with
      ART monotherapy or ACT long before the recent emergence of ART resistance. ART
      induced ring-stage dormancy and recovery have been implicated as possible causes
      of recrudescence; however, little is known about the characteristics of dormant
      parasites, including whether dormant parasites are metabolically active. We
      investigated the transcription of 12 genes encoding key enzymes in various
      metabolic pathways in P. falciparum during dihydroartemisinin (DHA)-induced
      dormancy and recovery. Transcription analysis showed an immediate downregulation
      for 10 genes following exposure to DHA but continued transcription of 2 genes
      encoding apicoplast and mitochondrial proteins. Transcription of several
      additional genes encoding apicoplast and mitochondrial proteins, particularly of
      genes encoding enzymes in pyruvate metabolism and fatty acid synthesis pathways,
      was also maintained. Additions of inhibitors for biotin acetyl-coenzyme A (CoA)
      carboxylase and enoyl-acyl carrier reductase of the fatty acid synthesis pathways
      delayed the recovery of dormant parasites by 6 and 4 days, respectively,
      following DHA treatment. Our results demonstrate that most metabolic pathways are
      downregulated in DHA-induced dormant parasites. In contrast, fatty acid and
      pyruvate metabolic pathways remain active. These findings highlight new targets
      to interrupt recovery of parasites from ART-induced dormancy and to reduce the
      rate of recrudescence following ART treatment. 

PMID- 24913168
TI  - Electrospun solid dispersions of Maraviroc for rapid intravaginal preexposure
      prophylaxis of HIV.
AB  - The development of topical anti-human immunodeficiency virus (HIV) microbicides
      may provide women with strategies to protect themselves against sexual HIV
      transmission. Pericoital drug delivery systems intended for use immediately
      before sex, such as microbicide gels, must deliver high drug doses for maximal
      effectiveness. The goal of achieving a high antiretroviral dose is complicated by
      the need to simultaneously retain the dose and quickly release drug compounds
      into the tissue. For drugs with limited solubility in vaginal gels, increasing
      the gel volume to increase the dose can result in leakage. While solid dosage
      forms like films and tablets increase retention, they often require more than 15
      min to fully dissolve, potentially increasing the risk of inducing epithelial
      abrasions during sex. Here, we demonstrate that water-soluble electrospun fibers,
      with their high surface area-to-volume ratio and ability to disperse
      antiretrovirals, can serve as an alternative solid dosage form for microbicides
      requiring both high drug loading and rapid hydration. We formulated maraviroc at
      up to 28 wt% into electrospun solid dispersions made from either
      polyvinylpyrrolidone or poly(ethylene oxide) nanofibers or microfibers and
      investigated the role of drug loading, distribution, and crystallinity in
      determining drug release rates into aqueous media. We show here that water
      soluble electrospun materials can rapidly release maraviroc upon contact with
      moisture and that drug delivery is faster (less than 6 min under sink conditions)
      when maraviroc is electrospun in polyvinylpyrrolidone fibers containing an
      excipient wetting agent. These materials offer an alternative dosage form to
      current pericoital microbicides. 

PMID- 24913169
TI  - Glucose-6-phosphate dehydrogenase status and risk of hemolysis in Plasmodium
      falciparum-infected African children receiving single-dose primaquine.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) enzyme function and genotype were
      determined in Ugandan children with uncomplicated falciparum malaria enrolled in
      a primaquine trial after exclusion of severe G6PD deficiency by fluorescent spot
      test. G6PD A- heterozygotes and hemizygotes/homozygotes experienced dose
      dependent lower hemoglobin concentrations after treatment. No severe anemia was
      observed. 

PMID- 24913170
TI  - Identification of a novel clone, ST736, among Enterococcus faecium clinical
      isolates and its association with daptomycin nonsusceptibility.
AB  - Resistance to daptomycin in enterococcal clinical isolates remains rare but is
      being increasingly reported in the United States and worldwide. There are limited
      data on the genetic relatedness and microbiological and clinical characteristics
      of daptomycin-nonsusceptible enterococcal clinical isolates. In this study, we
      assessed the population genetics of daptomycin-nonsusceptible Enterococcus
      faecium (DNSE) clinical isolates by multilocus sequence typing (MLST) and whole
      genome sequencing analysis. Forty-two nonduplicate DNSE isolates and 43 randomly
      selected daptomycin-susceptible E. faecium isolates were included in the
      analysis. All E. faecium isolates were recovered from patients at a tertiary care
      medical center in suburban New York City from May 2009 through December 2013. The
      daptomycin MICs of the DNSE isolates ranged from 6 to >256 MUg/ml. Three major
      clones of E. faecium (ST18, ST412, and ST736) were identified among these
      clinical isolates by MLST and whole-genome sequence-based analysis. A newly
      recognized clone, ST736, was seen in 32 of 42 (76.2%) DNSE isolates and in only
      14 of 43 (32.6%) daptomycin-susceptible E. faecium isolates (P < 0.0001). This
      report provides evidence of the association between E. faecium clone ST736 and
      daptomycin nonsusceptibility. The identification and potential spread of this
      novel E. faecium clone and its association with daptomycin nonsusceptibility
      constitute a challenge for patient management and infection control at our
      medical center. 

PMID- 24913171
TI  - Leishmanicidal activities of novel synthetic furoxan and benzofuroxan
      derivatives.
AB  - A novel series of furoxan (1,2,5-oxadiazole 2-oxide) (compounds 3, 4a and -b, 13a
      and -b, and 14a to -f) and benzofuroxan (benzo[c][1,2,5]oxadiazole 1-oxide)
      (compounds 7 and 8a to -c) derivatives were synthesized, characterized, and
      evaluated for in vitro activity against promastigote and intracellular amastigote
      forms of Leishmania amazonensis. The furoxan derivatives exhibited the ability to
      generate nitric oxide at different levels (7.8% to 27.4%). The benzofuroxan
      derivative 8a was able to increase nitrite production in medium supernatant from
      murine macrophages infected with L. amazonensis at 0.75 mM after 48 h. Furoxan
      and benzofuroxan derivatives showed remarkable leishmanicidal activity against
      both promastigote and intracellular amastigote forms. Compounds 8a, 14a and -b,
      and 14d exerted selective leishmanicidal activities superior to those of
      amphotericin B and pentamidine. In vitro studies at pH 5.4 reveal that compound
      8a is stable until 8 h and that compound 14a behaves as a prodrug, releasing the
      active aldehyde 13a. These compounds have emerged as promising novel drug
      candidates for the treatment of leishmaniasis. 

PMID- 24913173
TI  - Heterogeneity of molecular resistance patterns in antimony-resistant field
      isolates of Leishmania species from the western Mediterranean area.
AB  - Antimonials remain the first-line treatment for the various manifestations of
      leishmaniasis in most areas where the disease is endemic, and increasing cases of
      therapeutic failure associated with parasite resistance have been reported. In
      this study, we assessed the molecular status of 47 clinical isolates of
      Leishmania causing visceral and cutaneous leishmaniasis from Algeria, Tunisia,
      and southern France. In total, we examined 14 genes that have been shown to
      exhibit significant variations in DNA amplification, mRNA levels, or protein
      expression with respect to resistance to antimonials. The gene status of each
      clinical isolate was assessed via qPCR and qRT-PCR. We then compared the
      molecular pattern against the phenotype determined via an in vitro sensitivity
      test of the clinical isolates against meglumine antimoniate, which is considered
      the reference technique. Our results demonstrate significant DNA amplification
      and/or RNA overexpression in 56% of the clinical isolates with the resistant
      phenotype. All clinical isolates that exhibited significant overexpression of at
      least 2 genes displayed a resistant phenotype. Among the 14 genes investigated,
      10 genes displayed either significant amplification or overexpression in at least
      1 clinical isolate; these genes are involved in several metabolic pathways.
      Moreover, various gene associations were observed depending on the clinical
      isolates, supporting the multifactorial nature of Leishmania resistance.
      Molecular resistance features were found in the 3 Leishmania species investigated
      (Leishmania infantum, Leishmania major, and Leishmania killicki). To our
      knowledge, this is the first report of the involvement of molecular resistance
      genes in field isolates of Leishmania major and Leishmania killicki with the
      resistance phenotype. 

PMID- 24913174
TI  - Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized
      Patients with Inflammatory Bowel Disease.
AB  - Patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC)
      and Crohn's disease (CD), have worse outcomes with Clostridium difficile
      infection (CDI), including increased readmissions, colectomy, and death. Oral
      vancomycin is recommended for the treatment of severe CDI, while metronidazole is
      the standard of care for nonsevere infection. We aimed to assess treatment
      outcomes of CDI in IBD. We conducted a retrospective observational study of
      inpatients with CDI and IBD from January 2006 through December 2010. CDI severity
      was assessed using published criteria. Outcomes included readmission for CDI
      within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114
      patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were
      more common among UC than CD patients (24.2% versus 9.6%; P=0.04). Same-admission
      colectomy occurred in 27.4% of UC patients and 0% of CD patients (P<0.01). Severe
      CDI was more common among UC than CD patients (32.2% versus 19.4%; P=0.12) but
      not statistically significant. Two patients died from CDI-associated
      complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer
      readmissions and shorter lengths of stay when treated with a vancomycin
      containing regimen compared to those treated with metronidazole (30-day
      readmissions, 31.0% versus 0% [P=0.04]; length of stay, 13.62 days versus 6.38
      days [P=0.02]). Patients with UC and nonsevere CDI have fewer readmissions and
      shorter lengths of stay when treated with a vancomycin-containing regimen
      relative to those treated with metronidazole alone. Patients with ulcerative
      colitis and CDI should be treated with vancomycin.

PMID- 24913175
TI  - Downregulation of cellular c-Jun N-terminal protein kinase and NF-kappaB
      activation by berberine may result in inhibition of herpes simplex virus
      replication.
AB  - Berberine is a quaternary ammonium salt from the protoberberine group of
      isoquinoline alkaloids. Some reports show that berberine exhibits anti
      inflammatory, antitumor, and antiviral properties by modulating multiple cellular
      signaling pathways, including p53, nuclear factor kappaB (NF-kappaB), and mitogen
      activated protein kinase. In the present study, we investigated the antiviral
      effect of berberine against herpes simplex virus (HSV) infection. Current
      antiherpes medicines such as acyclovir can lessen the recurring activation when
      used early at infection but are unable to prevent or cure infections where
      treatment has selected for resistant mutants. In searching for new antiviral
      agents against herpesvirus infection, we found that berberine reduced viral RNA
      transcription, protein synthesis, and virus titers in a dose-dependent manner. To
      elucidate the mechanism of its antiviral activity, the effect of berberine on the
      individual steps of viral replication cycle of HSV was investigated via time-of
      drug addition assay. We found that berberine acted at the early stage of HSV
      replication cycle, between viral attachment/entry and genomic DNA replication,
      probably at the immediate-early gene expression stage. We further demonstrated
      that berberine significantly reduced HSV-induced NF-kappaB activation, as well as
      IkappaB-alpha degradation and p65 nuclear translocation. Moreover, we found that
      berberine also depressed HSV-induced c-Jun N-terminal kinase (JNK)
      phosphorylation but had little effect on p38 phosphorylation. Our results suggest
      that the berberine inhibition of HSV infection may be mediated through modulating
      cellular JNK and NF-kappaB pathways. 

PMID- 24913172
TI  - KAF156 is an antimalarial clinical candidate with potential for use in
      prophylaxis, treatment, and prevention of disease transmission.
AB  - Renewed global efforts toward malaria eradication have highlighted the need for
      novel antimalarial agents with activity against multiple stages of the parasite
      life cycle. We have previously reported the discovery of a novel class of
      antimalarial compounds in the imidazolopiperazine series that have activity in
      the prevention and treatment of blood stage infection in a mouse model of
      malaria. Consistent with the previously reported activity profile of this series,
      the clinical candidate KAF156 shows blood schizonticidal activity with 50%
      inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive
      and drug-resistant strains, as well as potent therapeutic activity in a mouse
      models of malaria with 50, 90, and 99% effective doses of 0.6, 0.9, and 1.4
      mg/kg, respectively. When administered prophylactically in a sporozoite challenge
      mouse model, KAF156 is completely protective as a single oral dose of 10 mg/kg.
      Finally, KAF156 displays potent Plasmodium transmission blocking activities both
      in vitro and in vivo. Collectively, our data suggest that KAF156, currently under
      evaluation in clinical trials, has the potential to treat, prevent, and block the
      transmission of malaria. 

PMID- 24913176
TI  - Structure-activity relationship study of the plant-derived decapeptide OSIP108
      inhibiting Candida albicans biofilm formation.
AB  - We performed a structure-activity relationship study of the antibiofilm plant
      derived decapeptide OSIP108. Introduction of positively charged amino acids R, H,
      and K resulted in an up-to-5-fold-increased antibiofilm activity against Candida
      albicans compared to native OSIP108, whereas replacement of R9 resulted in
      complete abolishment of its antibiofilm activity. By combining the most promising
      amino acid substitutions, we found that the double-substituted OSIP108 analogue
      Q6R/G7K had an 8-fold-increased antibiofilm activity. 

PMID- 24913177
TI  - Effect of periodontal therapy on lactoferrin levels in gingival crevicular fluid.
AB  - BACKGROUND: The aim of this study was to evaluate lactoferrin quantification as a
      sensitive and objective method of detecting the degree of periodontal
      inflammation, oxidative stress and to monitor the effects of periodontal therapy.
      METHODS: Fifty subjects were divided into two groups based on gingival index,
      probing pocket depth, clinical attachment loss and alveolar bone loss: healthy
      group and periodontitis group with generalized chronic periodontitis. Non
      surgical periodontal therapy was rendered and crevicular fluid samples collected
      at baseline and four weeks after therapy for lactoferrin quantification using
      enzyme linked immunosorbent assay. The correlation between clinical parameters
      and lactoferrin levels was drawn and analysed for both groups. RESULTS: The mean
      level of crevicular lactoferrin in the periodontitis group was 1857.21 ng/ml. The
      mean level decreased to 1415.03 ng/ml after treatment. The lowest lactoferrin
      concentration was seen in the healthy group (75.34 ng/ml). All clinical
      parameters correlated positively with lactoferrin levels. CONCLUSIONS: The
      lactoferrin level was higher in the periodontitis group compared to the healthy
      group, and reduced with periodontal therapy. Higher levels were associated with
      higher values of clinical parameters, both before and after therapy. The data
      indicates that Lactoferrin plays an important role in periodontal disease and
      crevicular lactoferrin quantification can be a marker for detecting periodontal
      inflammation, oxidative stress and monitoring periodontal therapy.

PMID- 24913178
TI  - Editorial Comment to Health-related quality of life after radical cystectomy and
      neobladder reconstruction in women: impact of voiding and continence status.

PMID- 24913179
TI  - Characteristics of cancer patients presenting to an integrative medicine practice
      based research network.
AB  - OBJECTIVE: To assess psychosocial characteristics, symptoms and reasons for
      seeking integrative medicine (IM) care in cancer patients presenting to IM
      clinical practices. STUDY DESIGN AND METHODS: A survey of 3940 patients was
      conducted at 8 IM sites. Patient reported outcome measures were collected and
      clinicians provided health status data. This analysis compares 353 participants
      self-identified as cancer patients with the larger noncancer cohort. RESULTS:
      Mean age of the cancer cohort was 55.0 years. Participants were predominantly
      white (85.9%), female (76.4%), and well educated (80.5% completed college). For
      15.2% of cancer patients, depression scores were consistent with depressive
      symptoms, and average scores for perceived stress were higher than normal, but
      neither were significantly different from noncancer patients. The most prevalent
      comorbid symptoms were chronic pain (39.8%), fatigue (33.5%), and insomnia
      (23.3%). In the cancer cohort, perceived stress was significantly associated with
      depression, fatigue, insomnia, pain, and QOL. Cancer patients who chose an IM
      clinical practice "seeking healthcare settings that address spirituality as an
      aspect of care" had significantly higher levels of perceived stress, depression,
      and pain than those not selecting this reason. CONCLUSIONS: Demographic
      characteristics, depression scores, perceived stress scores, and reasons for
      seeking integrative cancer care were not significantly different between cancer
      patients and noncancer patients. Perceived stress may be an important indicator
      of QOL. The association of perceived stress, depression and pain with seeking
      spirituality suggests that providing IM interventions, such as effective stress
      management techniques and pastoral or spiritual counseling, may be helpful to
      patients living with cancer.

PMID- 24913180
TI  - ShRNA-mediated Bmi-1 silencing sensitizes multiple myeloma cells to bortezomib.
AB  - The introduction of bortezomib has resulted in a paradigm shift in the treatment
      of multiple myeloma (MM) and has contributed to the improved survival of patients
      with MM. Inevitably, resistance to therapy develops, and thus the clinical
      efficacy of bortezomib is hampered by drug resistance. The oncogene B-cell
      specific Moloney murine leukemia virus insertion site-1 (Bmi-1) has been
      implicated in the pathogenesis of various human malignancies. Furthermore, RNA
      interference (RNAi)-mediated Bmi-1 silencing has been shown to sensitize tumor
      cells to chemotherapy and radiation. The role of Bmi-1 in influencing the
      response to bortezomib therapy has not been investigated to date. In the present
      study, Bmi-1 was silenced in two MM cell lines (U266 and RPMI8226) using short
      hairpin RNA (shRNA) targeting Bmi-1 (shBmi-1). A cell counting kit-8 (CCK-8)
      assay was performed to analyze cell proliferation and evaluate the 50% inhibitory
      concentration (IC50) values of bortezomib. Cell cycle progression and apoptosis
      were analyzed by flow cytometry (FCM), and the mRNA and protein expression of
      associated genes (Bmi-1, p14, p21, Bcl-2 and Bax) was quantified by RT-qPCR and
      western blot analysis, respectively. The IC50 values significantly decreased in
      the cells transfected with shBmi-1 (p<0.05). The depletion of Bmi-1 sensitized
      the MM cells to bortezomib, which increased the G1 phase duration and enhanced
      bortezomib-induced apoptosis (p<0.05). The expression of p21 and Bax (apoptosis
      inducer) was upregulated, whereas that of the anti-apoptotic protein, Bcl-2, was
      downregulated in the Bmi-1-silenced cells (p<0.05). The depletion of Bmi-1
      enhanced the sensitivity of MM cells to bortezomib by inhibiting cell
      proliferation and inducing cell cycle arrest and apoptosis. Our data suggest that
      Bmi-1 may serve as an important novel therapeutic target in MM.

PMID- 24913181
TI  - Aerococcus urinae: a possible reason for malodorous urine in otherwise healthy
      children.
AB  - Recently, Aerococcus urinae, primarily recognized as a common pathogen in elderly
      women, has been reported to cause an extremely unpleasant odour of the urine in
      paediatric patients similar to trimethylaminuria (fish odour syndrome). Herein,
      we present a case of A. urinae urinary tract colonization in a 12-year-old
      otherwise healthy boy, who finally refused micturition outside from his home
      environment as a result of the unpleasant odour. Within the last year, three
      cases (including our own) of A. urinae colonization causing foul-smelling urine
      in healthy children have been published, suggesting that this condition might be
      as frequent as trimethylaminuria. In case of polymicrobial growth in a urine
      specimen, A. urinae as the leading pathogen will usually be missed by routine
      bacteriological investigation. Novel bacteriological techniques such as MALDI-TOF
      MS provide a rapid tool to recognize this pathogen in urine. CONCLUSION: As
      treatment of A. urinae infection is simple, we recommend that in healthy children
      with malodorous urine, this pathogen is excluded before the initiation of costly
      metabolic investigations.

PMID- 24913183
TI  - Bilateral hearing loss is associated with decreased nonverbal intelligence in US
      children aged 6 to 16 years.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the association between hearing loss and
      nonverbal intelligence in US children. STUDY DESIGN: The Third National Health
      and Nutrition Examination Survey (NHANES III) is a cross-sectional survey (1988
      1994) that used complex multistage sampling design to produce nationally
      representative demographic and examination data. METHODS: A total of 4,823
      children ages 6 to 16 years completed audiometric evaluation and cognitive
      testing during NHANES III. Hearing loss was defined as low-frequency pure-tone
      average (PTA) >25 dB (0.5, 1, 2 kHz) or high-frequency PTA >25 dB (3, 4, 6, 8
      kHz) and was designated as unilateral or bilateral. Nonverbal intelligence was
      measured using the Wechsler Intelligence Scale for Children-Revised block design
      subtest. Low nonverbal intelligence was defined as a standardized score <4, two
      standard deviations below the standardized mean of 10. RESULTS: Mean nonverbal
      intelligence scores differed between children with normal hearing (9.59) and
      children with bilateral (6.87; P = .02) but not unilateral (9.12; P = .42)
      hearing loss. Non-Hispanic black race/ethnicity and family income <$20,000 were
      associated with 3.92 and 1.67 times higher odds of low nonverbal intelligence,
      respectively (odds ratio [OR]: 3.92; P < .001; OR: 1.67; P = .02). Bilateral
      hearing loss was independently associated with 5.77 times increased odds of low
      nonverbal intelligence compared to normal hearing children (OR: 5.77; P = .02).
      Unilateral hearing loss was not associated with higher odds of low nonverbal
      intelligence (OR: 0.73; P = .40). CONCLUSIONS: Bilateral but not unilateral
      hearing loss is associated with decreased nonverbal intelligence in US children.
      Longitudinal studies are urgently needed to better understand these associations
      and their potential impact on future opportunities.

PMID- 24913182
TI  - Influence of asymmetric recurrent laryngeal nerve stimulation on vibration,
      acoustics, and aerodynamics.
AB  - OBJECTIVES/HYPOTHESIS: Evaluate the influence of asymmetric recurrent laryngeal
      nerve (RLN) stimulation on the vibratory phase, acoustics and aerodynamics of
      phonation. STUDY DESIGN: Basic science study using an in vivo canine model.
      METHODS: The RLNs were symmetrically and asymmetrically stimulated over eight
      graded levels to test a range of vocal fold activation conditions from subtle
      paresis to paralysis. Vibratory phase, fundamental frequency (F0 ), subglottal
      pressure, and airflow were noted at phonation onset. The evaluations were
      repeated for three levels of symmetric superior laryngeal nerve (SLN)
      stimulation. RESULTS: Asymmetric laryngeal adductor activation from asymmetric
      left-right RLN stimulation led to a consistent pattern of vibratory phase
      asymmetry, with the more activated vocal fold leading in the opening phase of the
      glottal cycle and in mucosal wave amplitude. Vibratory amplitude asymmetry was
      also observed, with more lateral excursion of the glottis of the less activated
      side. Onset fundamental frequency was higher with asymmetric activation because
      the two RLNs were synergistic in decreasing F0 , glottal width, and strain.
      Phonation onset pressure increased and airflow decreased with symmetric RLN
      activation. CONCLUSION: Asymmetric laryngeal activation from RLN paresis and
      paralysis has consistent effects on vocal fold vibration, acoustics, and
      aerodynamics. This information may be useful in diagnosis and management of vocal
      fold paresis. LEVEL OF EVIDENCE: N/A.

PMID- 24913184
TI  - Effects of human beta-defensin-3 on biofilm formation-regulating genes dltB and
      icaA in Staphylococcus aureus.
AB  - An understanding of the regulatory mechanisms that drive Staphylococcus aureus
      biofilm formation may lead to the development of an effective strategy to control
      the increasing number of refractory clinical infections it causes. The present
      study examined the effects of the antimicrobial agent human beta-defensin 3 (hBD
      3) and the antibiotics vancomycin and clindamycin on the expression of the S.
      aureus biofilm formation-regulating genes, icaA and dltB, during bacterial
      adhesion and biofilm formation. Transcription (mRNA) levels of dlt and ica genes
      were measured using quantitative polymerase chain reaction, and slimes of S.
      aureus biofilm were examined with confocal scanning laser microscopy during S.
      aureus adhesion and biofilm formation. Although hBD-3, vancomycin and clindamycin
      led to significantly attenuated biofilm formation, their treatment-associated
      effects on the mRNA expression of dlt and ica were not identical. Vancomycin and
      clindamycin induced sustained expression of the dlt and ica genes, which may be
      harnessed to induce biofilm formation. However, hBD-3 did not have a significant
      affect on the transcription level of dltB during either bacterial adhesion or
      biofilm formation. Therefore, the mechanism of hBD-3 that regulated the
      suppression of biofilm formation appears to differ from the mechanisms of
      vancomycin and clindamycin. 

PMID- 24913185
TI  - Nerve growth factor decreases in sympathetic and sensory nerves of rats with
      chronic heart failure.
AB  - Nerve growth factor (NGF) plays a critical role in the maintenance and survival
      of both sympathetic and sensory nerves. Also, NGF can regulate receptor
      expression and neuronal activity in the sympathetic and sensory neurons.
      Abnormalities in NGF regulation are observed in patients and animals with heart
      failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within
      the sympathetic and sensory nerves are not known. Thus, the ELISA method was used
      to assess the levels of NGF in the stellate ganglion (SG) and dorsal root
      ganglion (DRG) neurons of control rats and rats with chronic HF induced by
      myocardial infarction. Our data show for the first time that the levels of NGF
      were significantly decreased (P < 0.05) in the SG and DRG neurons 6-20 weeks
      after ligation of the coronary artery. In addition, a close relation was observed
      between the NGF levels and the left ventricular function. In conclusion, chronic
      HF impairs the expression of NGF in the sympathetic and sensory nerves. Given
      that sensory afferent nerves are engaged in the sympathetic nervous responses to
      somatic stimulation (i.e. muscle activity during exercise) via a reflex
      mechanism, our data indicate that NGF is likely responsible for the development
      of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic
      HF. 

PMID- 24913186
TI  - Human elastin polypeptides improve the biomechanical properties of three
      dimensional matrices through the regulation of elastogenesis.
AB  - The replacement of diseased tissues with biological substitutes with suitable
      biomechanical properties is one of the most important goal in tissue engineering.
      Collagen represents a satisfactory choice for scaffolds. Unfortunately, the lack
      of elasticity represents a restriction to a wide use of collagen for several
      applications. In this work, we studied the effect of human elastin-like
      polypeptide (HELP) as hybrid collagen-elastin matrices. In particular, we studied
      the biomechanical properties of collagen/HELP scaffolds considering several
      components involved in ECM remodeling (elastin, collagen, fibrillin, lectin-like
      receptor, metalloproteinases) and cell phenotype (myogenin, myosin heavy chain)
      with particular awareness for vascular tissue engineering applications. Elastin
      and collagen content resulted upregulated in collagen-HELP matrices, even showing
      an improved structural remodeling through the involvement of proteins to a ECM
      remodeling activity. Moreover, the hybrid matrices enhanced the contractile
      activity of C2C12 cells concurring to improve the mechanical properties of the
      scaffold. Finally, small-angle X-ray scattering analyses were performed to enable
      a very detailed analysis of the matrices at the nanoscale, comparing the
      scaffolds with native blood vessels. In conclusion, our work shows the use of
      recombinant HELP, as a very promising complement able to significantly improve
      the biomechanical properties of three-dimensional collagen matrices in terms of
      tensile stress and elastic modulus.

PMID- 24913187
TI  - Spatial epidemiology of hepatitis C virus infection in Egypt: analyses and
      implications.
AB  - Egypt has the highest hepatitis C virus (HCV) prevalence in the world (14.7%).
      The drivers of the HCV epidemic in Egypt are not well understood, but the mass
      parenteral antischistosomal therapy (PAT) campaigns in the second half of the
      20th century are believed to be the determinant of the high prevalence. We
      studied HCV exposure in Egypt at a microscale through spatial mapping and
      epidemiological description of HCV clustering. The source of data was the 2008
      Egypt Demographic and Health Survey. We identified clusters with high and low HCV
      prevalence and high and low PAT exposure using Kulldorff spatial scan statistics.
      Correlations across clusters were estimated, and each cluster age-specific HCV
      prevalence was described. We identified six clusters of high HCV prevalence,
      three clusters of low HCV prevalence, five clusters of high PAT exposure, and
      four clusters of low PAT exposure. HCV prevalence and PAT exposure were not
      significantly associated across clusters (Pearson correlation coefficient [PCC] =
      0.36; 95% confidence interval [CI] -0.12 to 0.71). Meanwhile, there was a strong
      association between HCV prevalence in individuals older than 30 years of age (who
      could have been exposed to PAT) and HCV prevalence in individuals 30 years of age
      or younger (who could not have been exposed to PAT) (PCC = 0.81; 95% CI 0.55
      0.93). CONCLUSION: The findings illustrate a spatial variation in HCV exposure in
      Egypt. The observed clustering was suggestive of an array of iatrogenic risk
      factors, besides past PAT exposure, and ongoing transmission. The role of PAT
      exposure in the HCV epidemic could have been overstated. Our findings support the
      rationale for spatially prioritized interventions.

PMID- 24913188
TI  - Inaugural bone metastases in non-small cell lung cancer: a specific prognostic
      entity?
AB  - BACKGROUND: In non-small cell lung cancer patients (NSCLC), median survival from
      the time patients develop bone metastasis is classically described being inferior
      to 6 months. We investigated the subcategory of patients having an inaugural
      skeletal-related-event revealing NSCLC. The purpose of this study was to assess
      the impact of bone involvement on overall survival and to determine biological
      and tumoral prognosis factors on OS and PFS. An analysis of the subgroup of
      solitary bone metastasis patients was also performed. METHODS: In a population of
      1208 lung cancer patients, 55 consecutive NSCLC patients revealed by inaugural
      bone metastasis and treated between 2003 and 2010, were retrospectively analysed.
      Survival was measured with a Kaplan-Meyer curve. Univariate and multivariate
      analysis were performed using the Stepwise Cox proportional hazard regression
      model. A p value of less than 0,05 was considered statistically significant.
      RESULTS: Estimated incidence of revealing bone metastasis is 4,5% among newly
      diagnosed lung cancer patients. Median duration of skeletal symptoms before
      diagnosis was 3 months and revealing bone site was located on axial skeleton in
      70% of the cases. Histology was adenocarcinoma (78%), with small primary tumors
      Tx-T1-2 accounting for 71% of patients. Rate of second SRE is 37%.Median overall
      survival was 8.15 months, IQR [5-16 months], mean survival 13.4 months, and PFS
      was 3.5 months. In multivariate analysis, variables significantly associated with
      shortened survival were advanced T stage (HR=2.8; p=0.004), weight loss>10%
      (HR=3.1; p=0.02), inaugural spinal epidural metastasis (HR 2.5; p=0.0036),
      elevated C-reactive protein (HR=4.3; p=0.002) and TTF-1 status (HR=2.42;
      p=0.004). Inaugural spinal epidural metastasis is a very strong adverse pronostic
      factor in these cases, with a 3 months median survival. Single bone metastasis
      patients showed prolonged survival of 14.2 months versus 7.6 months, only in
      univariate analysis (HR=0.42; p=0.0059). CONCLUSION: Prognosis of lung cancer
      patients with inaugural SRE remains pejorative. Accurately estimating the
      survival of this population is helpful for bone surgical decision-making at
      diagnosis. The trend for a higher proportion of adenocarcinoma in NSCLC patients
      should result with an increasing number of patients with inaugural SRE at
      diagnosis.

PMID- 24913189
TI  - Biomechanical comparison of different combinations of hook and screw in one spine
      motion unit--an experiment in porcine model.
AB  - BACKGROUND: The biomechanical performance of the hooks and screws in spinal
      posterior instrumentation is not well-characterized. Screw-bone interface failure
      at the uppermost and lowermost vertebrae is not uncommon. Some have advocated for
      the use of supplement hooks to prevent screw loosening. However, studies
      describing methods for combined hook and screw systems that fully address the
      benefits of these systems are lacking. Thus, the choice of which implant to use
      in a given case is often based solely on a surgeon's experience instead of on the
      biomechanical features and advantages of each device. METHODS: We conducted a
      biomechanical comparison of devices instrumented with different combinations of
      hooks and screws. Thirty-six fresh low thoracic porcine spines were assigned to
      three groups (12 per group) according to the configuration used for of fixation:
      (1) pedicle screw; (2) lamina hook and (3) combination of pedicle screw and
      lamina hook. Axial pullout tests backward on transverse plane in the direction
      normal to the rods were performed using a material testing machine and a
      specially designed grip with self-aligned function. RESULTS: The pullout force
      for the pedicle screws group was significantly greater than for the hooks and the
      combination (p < 0.05). However, no significant difference was found between the
      hooks and the combination (p > 0.05). CONCLUSIONS: Pedicle screws achieve the
      maximal pullout strength for spinal posterior instrumentation.

PMID- 24913190
TI  - First-trimester prediction of pre-eclampsia: external validity of algorithms in a
      prospectively enrolled cohort.
AB  - OBJECTIVE: To evaluate the performance of published first-trimester prediction
      algorithms for pre-eclampsia (PE) in a prospectively enrolled cohort of women.
      METHOD: A MEDLINE search identified first-trimester screening-prediction
      algorithms for early-onset (requiring delivery < 34 weeks) and late-onset
      (requiring delivery >= 34 weeks) PE. Maternal variables, ultrasound parameters
      and biomarkers were determined prospectively in singleton pregnancies enrolled
      between 9 and 14 weeks. Prediction algorithms were applied to this population to
      calculate predicted probabilities for PE. The performance of the prediction
      algorithms was compared with that in the original publication and evaluated for
      factors explaining differences in prediction. RESULTS: Six early and two late PE
      prediction algorithms were applicable to 871-2962 women, depending on the
      variables required. The prevalence of early PE was 1.0-1.2% and of late PE was
      4.1-5.0% in these patient subsets. One early PE prediction algorithm performed
      better than in the original publication (80% detection rate (DR) of early PE for
      10% false-positive rate (FPR)); the remaining five prediction algorithms
      underperformed (29-53% DR). Prediction algorithms for late PE also underperformed
      (18-31% DR, 10% FPR). Applying the screening cut-offs based on the highest Youden
      index probability scores correctly detected 40-80% of women developing early PE
      and 71-82% who developed late PE. Exclusion of patients on first-trimester
      aspirin resulted in DRs of 40-83% and 65-82% for early and late PE, respectively.
      CONCLUSION: First-trimester prediction algorithms for PE share a high negative
      predictive value if applied to an external population but underperform in their
      ability to correctly identify women who develop PE. Further research is required
      to determine the factors responsible for the suboptimal external validity.

PMID- 24913192
TI  - Mediator redefines itself.
AB  - Mediator is a large and structurally dynamic protein complex that is globally
      required for eukaryotic transcription by RNA polymerase II. In a recent paper
      published in Cell Research, Wang et al. report for the first time the location of
      distinct subunits and redefine domains in the S. cerevisiae Mediator complex. 

PMID- 24913194
TI  - Can nanotechnology deliver the promised benefits without negatively impacting
      soil microbial life?
AB  - Nanotechnology exploits the enhanced reactivity of materials at the atomic scale
      to improve various applications for humankind. In agriculture, potential
      nanotechnology applications include crop protection and fertilization. However,
      such benefits could come with risks for the environment: non-target plants, plant
      beneficial soil microbes and other life forms could be impacted if nanoparticles
      (nanomaterials) contaminate the environment. This review evaluates the impact of
      the major metallic nanoparticles (Ag, ZnO, CuO, CeO2 , TiO2 , and FeO-based
      nanoparticles) on soil microbes involved in agricultural processes. The current
      literature indicate that in addition to population and organismal-scale effects
      on microbes, other subtle impacts of nanoparticles are seen in the nitrogen
      cycle, soil enzyme activities, and processes involved in iron metabolism,
      phytohormone, and antibiotic production. These effects are negative or positive,
      the outcome being dependent on specific nanoparticles. Collectively, published
      results suggest that nanotechnology portends considerable, many negative,
      implications for soil microbes and, thus, agricultural processes that are
      microbially driven. Nonetheless, the potential of plant and soil microbial
      processes to mitigate the bioreactivity of nanoparticles also are observed.
      Whereas the roots of most terrestrial plants are associated with microbes,
      studies of nanoparticle interactions with plants and microbes are generally
      conducted separately. The few studies in actual microbe-plant systems found
      effects of nanoparticles on the functioning of arbuscular mycorrhizal fungi,
      nitrogen fixation, as well as on the production of microbial siderophores in the
      plant rhizosphere. It is suggested that a better understanding of the agro
      ecological ramifications of nanoparticles would require more in-depth interactive
      studies in combined plant-microbe-nanoparticle systems. 

PMID- 24913193
TI  - De novo mutation in ATP6V1B2 impairs lysosome acidification and causes dominant
      deafness-onychodystrophy syndrome.

PMID- 24913191
TI  - Shh-proteoglycan interactions regulate maturation of olfactory glomerular
      circuitry.
AB  - The olfactory system relies on precise circuitry connecting olfactory sensory
      neurons (OSNs) and appropriate relay and processing neurons of the olfactory bulb
      (OB). In mammals, the exact correspondence between specific olfactory receptor
      types and individual glomeruli enables a spatially precise map of glomerular
      activation that corresponds to distinct odors. However, the mechanisms that
      govern the establishment and maintenance of the glomerular circuitry are largely
      unknown. Here we show that high levels of Sonic Hedgehog (Shh) signaling at
      multiple sites enable refinement and maintenance of olfactory glomerular
      circuitry. Mice expressing a mutant version of Shh (Shh(Ala/Ala)), with impaired
      binding to proteoglycan co-receptors, exhibit disproportionately small olfactory
      bulbs containing fewer glomeruli. Notably, in mutant animals the correspondence
      between individual glomeruli and specific olfactory receptors is lost, as
      olfactory sensory neurons expressing different olfactory receptors converge on
      the same glomeruli. These deficits arise at late stages in post-natal development
      and continue into adulthood, indicating impaired pruning of erroneous connections
      within the olfactory bulb. In addition, mature Shh(Ala/Ala) mice exhibit
      decreased proliferation in the subventricular zone (SVZ), with particular
      reduction in neurogenesis of calbindin-expressing periglomerular cells. Thus, Shh
      interactions with proteoglycan co-receptors function at multiple locations to
      regulate neurogenesis and precise olfactory connectivity, thereby promoting
      functional neuronal circuitry.

PMID- 24913195
TI  - Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of
      JAK2 be recognized as specific entities?
AB  - Since the publication of the 2001 and 2008 World Health Organization
      classifications of tumours of haematopoietic and lymphoid tissues, there has been
      an increasing move towards classification of haematological neoplasms on the
      basis of the underlying molecular genetic disorder. In recent decades there have
      been a significant number of reports of haematological neoplasms with
      rearrangement of JAK2. Published data on such cases have therefore been analysed
      to determine if any specific entities could be identified. On the basis of this
      analysis, it is suggested that lymphoid and myeloid neoplasms associated with
      t(8;9)(p22;p24); PCM1-JAK2 fusion should be recognized as an entity. Furthermore,
      lymphoid and myeloid neoplasms associated respectively with t(9;12)(p24;p13);
      ETV6-JAK2 and with t(9;22)(p24;q11.2); BCR-JAK2 should be documented carefully in
      order to define their features more clearly and assess whether they can be
      recognized as entities. Identification of all these conditions is important
      because of the possibility of response to JAK2 inhibitors. 

PMID- 24913196
TI  - What lies inside the cup?

PMID- 24913197
TI  - High clopidogrel dose in patients with chronic kidney disease having clopidogrel
      resistance after percutaneous coronary intervention.
AB  - We evaluated the impact of clopidogrel 150 mg/d in patients with chronic kidney
      disease (CKD) having clopidogrel resistance (CR) after percutaneous coronary
      intervention (PCI); 1076 consecutive patients with coronary artery disease (CAD)
      having CKD were enrolled. Maximal platelet aggregation (MPA) was assessed before,
      24 hours, and 30 days after a 300-mg loading dose of clopidogrel prior to PCI.
      After PCI, 370 patients with CR were randomized to receive clopidogrel 75 mg/d (n
      = 184) or 150 mg/d (n = 186) for 30 days. Stent thrombosis (ST), major adverse
      cardiac events (MACEs), and bleeding were analyzed after 1 month. Patients in the
      150 mg group had significant lower rates of ST and MACE. There was no significant
      difference in major or minor bleeding. Patients in the 150 mg group had lower MPA
      and greater inhibition of platelet aggregation. One-month administration of 150
      mg/d of clopidogrel decreases the rate of ST and MACE without increasing bleeding
      in patients with CKD having CR after PCI. 

PMID- 24913198
TI  - Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes
      requires higher pegvisomant doses to normalise IGF1 levels.
AB  - OBJECTIVE: Acromegaly is associated with an increased prevalence of glucose
      metabolism disorders. Clinically confirmed diabetes mellitus is observed in
      approximately one quarter of all patients with acromegaly and is known to have a
      worse prognosis in these patients. DESIGN: Of 514 acromegalic patients treated
      with pegvisomant and recorded in the German Cohort of ACROSTUDY, 147 had
      concomitant diabetes mellitus. We analysed these patients in an observational
      study and compared patients with and without concomitant diabetes. RESULTS: Under
      treatment with pegvisomant, patients with diabetes mellitus rarely achieved
      normalisation (64% in the diabetic cohort vs 75% in the non-diabetic cohort,
      P=0.04) for IGF1. Diabetic patients normalised for IGF1 required higher
      pegvisomant doses (18.9 vs 15.5 mg pegvisomant/day, P<0.01). Furthermore, those
      diabetic patients requiring insulin therapy showed a tendency towards requiring
      even higher pegvisomant doses to normalise IGF1 values than diabetic patients
      receiving only oral treatment (22.8 vs 17.2 mg pegvisomant/day, P=0.11).
      CONCLUSIONS: Hence, notable interdependences between the acromegaly, the glucose
      metabolism of predisposed patients and their treatment with pegvisomant were
      observed. Our data support recent findings suggesting that intra-portal insulin
      levels determine the GH receptor expression in the liver underlined by the fact
      that patients with concomitant diabetes mellitus, in particular those receiving
      insulin therapy, require higher pegvisomant doses to normalise IGF1. It is
      therefore important to analyse various therapy modalities to find out whether
      they influence the associated diabetes mellitus and/or whether the presence of
      diabetes mellitus influences the treatment results of an acromegaly therapy.

PMID- 24913199
TI  - Thyroidectomy in patients with a high BMI: a safe surgery?
AB  - OBJECTIVE: To study and compare the specific postoperative complications of
      thyroidectomy in a population with a BMI >=25 with a population having a BMI
      below 25. DESIGN: A prospective study was carried out from September 2010 to
      January 2013. METHODS: Postoperative calcemia, laryngeal mobility, bleeding or
      infectious complications, postoperative hospital stay, and operation time were
      studied and compared statistically by a chi(2)-test or Student's t-test. RESULTS:
      A total of 240 patients underwent total thyroidectomy and 126 underwent a partial
      thyroidectomy. Of them, 168 patients had a BMI below 25 and 198 patients had a
      BMI >=25. There was no statistically significant difference in the occurrence of
      early or permanent hypoparathyroidism, recurrent laryngeal nerve palsy, bleeding
      complications, or postoperative duration of hospital stay. There was, however, a
      significant operative time in patients with a BMI >=25. CONCLUSION: Despite the
      longer operative time, thyroidectomy (total or partial) can be performed safely
      in patients with a BMI >=25.

PMID- 24913200
TI  - Motivational interviewing combined with chess accelerates improvement in
      executive functions in cocaine dependent patients: a one-month prospective study.
AB  - BACKGROUND: In cocaine-dependent individuals, executive function (EF) deficits
      are associated with poor treatment outcomes. Psychological interventions and
      pharmacological approaches have produced only modest effect sizes. To date,
      studies of this topic have been few and limited. The aim of this study was to
      examine the effects of a new model of intervention, which integrates chess and
      Motivational Interviewing, Motivational Chess (MC) METHODS: We evaluated 46
      cocaine-dependent inpatients (aged 18-45), in two groups-MC (n=26); and active
      comparison-AC (n=20). Using neuropsychological tests and an impulsivity scale, we
      assessed the subjects before and after the study period (one month of abstinence
      monitored by urine toxicology screening). RESULTS: The MC and AC groups did not
      differ at baseline. In the post-intervention assessment (after one month), both
      groups showed significant improvements in attention, mental flexibility,
      inhibitory control, abstraction abilities, and decision-making (p<0.01). In
      addition, the improvement in working memory was more significant in the MC group
      than in the AC group (group-by-time interaction, p=01). CONCLUSIONS: One month of
      abstinence was sufficient to improve various attentional and executive domains in
      cocaine-dependent subjects. The MC intervention was associated with greater
      improvements in EFs, especially working memory, suggesting that tailored
      interventions focusing on complex EFs accelerate the process of cognitive
      recovery during the initial period of abstinence.

PMID- 24913201
TI  - Sleep disturbance among women with chronic pelvic pain.
AB  - OBJECTIVE: To investigate the effect of chronic pelvic pain (CPP), a debilitating
      condition, on sleep quality. METHODS: The present case-control study enrolled
      women older than 18 years attending the Gynecology Clinic of Canakkale Onsekiz
      Mart University Hospital, Canakkale, Turkey, with CPP between August 2011 and
      August 2012. The control group was selected from women attending the clinic for
      another complaint. Sleep quality was evaluated via the Pittsburgh Sleep Quality
      Index, and differences between the groups were compared by t and chi(2) tests.
      RESULTS: During the study period, 157 women were enrolled. Seventy-two had CPP
      symptoms, and 85 attended the clinic for other complaints. Poor sleep quality was
      found in 80% (n = 58) of the women with CPP, and 55% (n = 47) of the control
      group (P < 0.05). CONCLUSION: Women with CPP were found to have poor sleep
      quality. Sleep education should be recommended in psychiatry and neurology
      clinics to increase the awareness of sleeping problems among these women.

PMID- 24913202
TI  - Placental proteome alterations in women with intrahepatic cholestasis of
      pregnancy.
AB  - OBJECTIVE: To investigate differences in the placental proteomes of women with
      intrahepatic cholestasis of pregnancy (ICP) and those with a normal pregnancy.
      METHODS: Ten pregnant women diagnosed with ICP were recruited at the First
      People's Hospital of Yuhang District from October 2011 to September 2012; 10 age
      matched healthy pregnant women acted as controls. Total placental proteins were
      extracted and subjected to two-dimensional polyacrylamide gel electrophoresis
      followed by mass spectrometry to identify proteins that were differentially
      expressed in the two groups. RESULTS: In total, 37 protein spots with
      differentially expressed proteins were found. These comprised proteins involved
      in cytoskeleton activity, blood coagulation, and platelet activation as well as
      chaperones, heat shock proteins, RNA-binding and calcium-binding proteins, and
      various enzymes. CONCLUSION: The placentas of women with ICP displayed
      significant proteome differences compared with women with a normal pregnancy. The
      results indicate that a variety of mechanisms and proteins may contribute to the
      development of ICP. Further verification and research are required to elucidate
      the exact roles of these proteins in ICP pathogenesis.

PMID- 24913203
TI  - Three years of data on the impact of obstetrician/gynecologist coverage in rural
      Uganda.

PMID- 24913204
TI  - Oral administration of inosine promotes recovery after experimental spinal cord
      injury in rat.
AB  - Inosine, a purine nucleoside, is one of the novel substances, which can preserve
      the neuronal and glial viability and stimulate intact neurons to extend axons.
      We, herein, evaluated the effect of oral inosine treatment on spinal cord injury
      (SCI) recovery by means of locomotor and bladder function, quantification of
      neurons and spinal cord tissue sparing. Rats after compression SCI were divided
      into groups-SCI-Aqua and SCI-Inosine (daily application of aqua for injection or
      inosine)-locomotion of hind limbs (BBB score) and urinary bladder function were
      evaluated from day 1 to 28 after SCI. The neuronal profile was determined by
      immunohistochemistry with NeuN antibodies and tissue sparing by Luxol fast blue
      staining method. SCI affected the functional movement of hind limbs in both
      groups with gradual improvement (increased BBB score) during survival. However,
      we found a significant difference in BBB score and recovery of bladder function
      between SCI-Aqua and SCI-Inosine groups during the second week of survival
      following SCI. In addition, the number of NeuN positive cells and percentage of
      tissue sparing was also significantly higher in SCI-Inosine group when compared
      with the SCI-Aqua group. Daily oral administration of inosine after SCI
      throughout the survival was beneficial for locomotion and micturition, neuronal
      survival and tissue sparing. This indicates that inosine may represent one of the
      co-stimulatory factors for treatment strategies to promote neuronal plasticity
      after SCI. 

PMID- 24913206
TI  - Why have the complications of diabetes mellitus declined over the past 30 years?

PMID- 24913205
TI  - Cell death in amastigote forms of Leishmania amazonensis induced by parthenolide.
AB  - BACKGROUND: Leishmania amazonensis infection results in diverse clinical
      manifestations: cutaneous, mucocutaneous or visceral leishmaniasis. The arsenal
      of drugs available for treating Leishmania infections is limited. Therefore, new,
      effective, and less toxic leishmaniasis treatments are still needed. We verified
      cell death in amastigote forms of Leishmania amazonensis induced by the
      sesquiterpene lactone parthenolide. RESULTS: The tested compound was able to
      concentration-dependently affect axenic and intracellular amastigotes, with IC50
      values of 1.3 MUM and 2.9 MUM, respectively after 72 h incubation. No genotoxic
      effects were observed in a micronucleus test in mice. Parthenolide induced
      morphological and ultrastructural changes in axenic amastigotes, including a loss
      of membrane integrity, swelling of the mitochondrion, cytoplasmic vacuoles, and
      intense exocytic activity in the region of the flagellar pocket. These results
      led us to investigate the occurrence of autophagic vacuoles with
      monodansylcadaverine and the integrity of the plasma membrane and mitochondrial
      membrane potential using flow cytometry. In all of the tests, parthenolide had
      positive results. CONCLUSIONS: Our results indicate that the antileishmanial
      action of parthenolide is associated with autophagic vacuole appearance, a
      reduction of fluidity, a loss of membrane integrity, and mitochondrial
      dysfunction. Considering the limited repertoire of existing antileishmanial
      compounds, the products derived from medicinal plants has been one the greatest
      advances to help develop new chemotherapeutic approaches.

PMID- 24913208
TI  - Brain games to slow cognitive decline in Alzheimer's disease.

PMID- 24913209
TI  - Telemedicine and the evaluation of cognitive impairment: the additive value of
      neuropsychological assessment.
AB  - INTRODUCTION: The number of people in the United States living with dementia is
      projected to rise to over 7.1 million in the next 12 years, representing a 40%
      increase from current levels. This anticipated "dementia tsunami" has led to a
      recent state and national policy emphasis on early detection, improved care
      quality, reduced caregiver burden, and increased access to care. The ability to
      achieve these objectives is limited by few dementia specialists in rural and
      small communities and the challenges of travel to and within congested urban
      regions for dementia patients and their caregivers. Telemedicine is one such
      means for responding to this lack of access to subspecialty assessment and care.
      We describe our early experiences with this technology applied to
      neuropsychological assessments, with data from 31 patients. METHODS: As part of
      an interdisciplinary dementia care demonstration project, clinical video
      teleconferencing provides real-time high resolution video interactions between
      dementia subspecialists in a major metropolitan medical center and patients in 3
      outlying clinics located 180, 150, and 100 miles away. Comprehensive
      neuropsychological assessments, designed to address referral questions related to
      neurocognitive disorders via clinical video teleconferencing, are conducted as
      one component of interdisciplinary care. OUTCOMES: Eighty-seven percent of
      patients referred for neuropsychological assessment had an inaccurate
      neurocognitive diagnosis at the time of referral. Unmet and unrecognized mental
      health treatment needs were identified in over 77% of patients. In addition,
      acceptance was good for patients, caregivers, and clinicians. DISCUSSION:
      Teleneuropsychology is proving to be an excellent resource for clarifying
      cognitive and psychiatric diagnoses, and integrating individual strengths,
      weaknesses, and preferences into treatment and care plans used by other health
      care providers, patients, and caregivers.

PMID- 24913207
TI  - Nutritional status and the incidence of pneumonia in nursing home residents:
      results from the INCUR study.
AB  - OBJECTIVES: To examine the predictive value of the Mini Nutritional Assessment
      short form (MNA-SF) and its individual items on the incidence of pneumonia.
      DESIGN: Prospective observational cohort study over 1-year of follow-up.
      PARTICIPANTS: A total of 773 older persons (74.4% women) living in 13 French
      nursing homes from the Incidence of pNeumonia and related ConseqUences in nursing
      home Residents (INCUR) study. MEASUREMENTS: Nutritional status was assessed using
      the MNA-SF questionnaire at baseline. Diagnosis of pneumonia was based on
      clinical conditions retrieved from a medical chart. Cox proportional hazard
      models were applied to test whether the MNA-SF score and its single components
      predict pneumonia events over 1 year of follow-up. RESULTS: After 1 year of
      follow-up, 160 (21%) incident cases of pneumonia were recorded. Mean age of
      participants was 86.2 (SD 7.5) years. Mean MNA-SF score was 9.8 (SD 2.4), with
      more than half of the participants (58.7%) being at risk of malnutrition (8-11
      points). The total MNA-SF score and its categories did not predict the studied
      outcome. However, a single component of the MNA-SF score, specifically decreased
      mobility, was a significant risk factor for pneumonia (hazard ratio 2.289; 95%
      confidence interval 1.357-3.860; P = .002), independently of potential
      confounders. CONCLUSIONS: The total MNA-SF score did not predict the incidence of
      pneumonia. However, decreased mobility was a significant risk factor, implying
      that individual components of the MNA-SF should be more carefully explored to
      verify whether they might be used for detecting specific declines of the health
      status in nursing home residents, thus potentially improving the risk profile
      estimation of such a complex population.

PMID- 24913210
TI  - A randomized controlled trial on teaching geriatric medical decision making and
      cost consciousness with the serious game GeriatriX.
AB  - OBJECTIVE: Medical students often lack training in complex geriatric medical
      decision making. We therefore developed the serious game, GeriatriX, for training
      medical decision making with weighing patient preferences, and appropriateness
      and costs of medical care. We hypothesized that education with GeriatriX would
      improve the ability to deal with geriatric decision making and also increase cost
      consciousness. DESIGN: A randomized, controlled pre-post measurement design.
      PARTICIPANTS: Fifth-year medical students. INTERVENTION: Playing the serious game
      GeriatriX as an additive to usual geriatric education. MEASUREMENTS: We evaluated
      the effects of playing GeriatriX on self-perceived knowledge of geriatric themes
      and the self-perceived competence of weighing patient preferences,
      appropriateness, and costs of medical care in geriatric decision making. Cost
      consciousness was evaluated with a postmeasurement to estimate costs of different
      diagnostic tests. RESULTS: There was a large positive increase in the self
      perceived competence of weighing patient preferences, appropriateness, and costs
      of medical care in the intervention group (n = 71) (effect sizes of 0.7, 1.0, and
      1.2, respectively), which was significantly better for the last 2 aspects than in
      the control group (n = 63). The intervention group performed better on cost
      consciousness. Although the self-perceived knowledge increased substantially on
      some geriatric topics, this improvement was not different between the
      intervention and control groups. CONCLUSIONS: After playing the serious game,
      GeriatriX, medical students have a higher self-perceived competence in weighing
      patient preferences, appropriateness, and costs of medical care in complex
      geriatric medical decision making. Playing GeriatriX also resulted in better cost
      consciousness. We therefore encourage wider use of GeriatriX to teach geriatrics
      in medical curricula and its further research on educational and health care
      outcomes.

PMID- 24913211
TI  - Burdensome transitions at the end of life among long-term care residents with
      dementia.
AB  - OBJECTIVES: The purpose of the study was to examine the frequency of burdensome
      care transitions at the end of life, the difference between different types of
      residential care facilities, and the changes occurring between 2002 and 2008.
      DESIGN: A nationwide, register-based retrospective study. SETTING: Residential
      care facilities offering long-term care, including traditional nursing homes,
      sheltered housing with 24-hour assistance, and long-term care facilities
      specialized in care for people with dementia. STUDY GROUP: All people in Finland
      who died at the age of 70 or older, had dementia, and were in residential care
      during their last months of life. MAIN OUTCOME MEASURES: Three types of
      potentially burdensome care transition: (1) any transition to another care
      facility in the last 3 days of life; (2) a lack of continuity with respect to a
      residential care facility before and after hospitalization in the last 90 days of
      life; (3) multiple hospitalizations (more than 2) in the last 90 days of life.
      The 3 types were studied separately and as a whole. RESULTS: One-tenth (9.5%) had
      burdensome care transitions. Multiple hospitalizations in the last 90 days were
      the most frequent, followed by any transitions in the last 3 days of life. The
      frequency varied between residents who lived in different baseline care
      facilities being higher in sheltered housing and long-term specialist care for
      people with dementia than in traditional nursing homes. During the study years,
      the number of transitions fluctuated but showed a slight decrease since 2005.
      CONCLUSIONS: The ongoing change in long-term care from institutional care to
      housing services causes major challenges to the continuity of end-of-life care.
      To guarantee good quality during the last days of life for people with dementia,
      the underlying reasons behind transitions at the end of life should be
      investigated more thoroughly.

PMID- 24913212
TI  - The effect of dance on depressive symptoms in nursing home residents.
AB  - OBJECTIVE: To evaluate the effect of a dance-based therapy on depressive symptoms
      among institutionalized older adults. DESIGN: Randomized controlled trial.
      SETTING: Nursing homes. PARTICIPANTS: Older adults (60 years or older)
      permanently living in a nursing home. INTERVENTION: Exercise Dance for Seniors
      (EXDASE) Program designed for the use in long-term care settings performed once a
      week for 60 minutes for 3 months. MEASUREMENTS: Baseline measures included
      sociodemographic characteristics, ability to perform basic as well as
      instrumental activities of daily living, basic mobility, self-rated health, and
      cognitive status. Outcome measures were collected before and after the
      intervention and included assessment of depressive symptoms using the geriatric
      depression scale (GDS). RESULTS: Comparison of participants with MMSE of 15 or
      higher showed that GDS scores in the intervention group significantly improved (P
      = .005), whereas the control group had a trend of further worsening of depressive
      symptoms (P = .081). GLM analysis documented highly statistically significant
      effect of dance therapy (P = .001) that was not influenced by controlling for
      intake of antidepressants and nursing home location. Dance therapy may have
      decreased depressive symptoms even in participants with MMSE lower than 15 and
      resulted in more discontinuations and fewer prescriptions of antidepressants in
      the intervention group than in the control group. CONCLUSION: This study provides
      evidence that dance-based exercise can reduce the amount of depressive symptoms
      in nursing home residents. In general, this form of exercise seems to be very
      suitable and beneficial for this population.

PMID- 24913213
TI  - Do recovery expectations change over time?
AB  - PURPOSE: While a considerable body of research has explored the relationship
      between patient expectations and clinical outcomes, few studies investigate the
      extent to which patient expectations change over time. Further, the temporal
      relationship between expectations and symptoms is not well researched. METHODS:
      We conducted a latent class growth analysis on patients (n = 874) with back pain.
      Patients were categorised in latent profile clusters according to the course of
      their expectations over 3 months. RESULTS: Nearly 80% of participants showed a
      pattern of stable expectation levels, these patients had either high, medium or
      low levels of expectations for the whole study period. While baseline levels of
      symptom severity did not discriminate between the three clusters, those in the
      groups with higher expectations experienced better outcome at 3 months.
      Approximately 15% of patients showed decrease in expectation levels over the
      study period and the remainder were categorised in a group with increasingly
      positive expectations. In the former clusters, decrease in expectations appeared
      to be concordant with a plateau in symptom improvement, and in the latter,
      increase in expectations occurred alongside an increase in symptom improvement
      rate. CONCLUSIONS: The expectations of most people presenting to primary care
      with low back pain do not change over the first 3 months of their condition.
      People with very positive, stable expectations generally experience a good
      outcome. While we attempted to identify a causal influence of expectations on
      symptom severity, or vice versa, we were unable to demonstrate either
      conclusively.

PMID- 24913214
TI  - Effect of Modic changes on spinal canal stenosis and segmental motion in cervical
      spine.
AB  - PURPOSE: Few studies have reported the characteristics of Modic changes (MCs) in
      the cervical spine in contrast to the lumbar spine. The purpose of this study was
      to identify the prevalence of MCs in the cervical spine and to elucidate the
      relationship of MCs with spinal canal stenosis and angular motion. METHODS: 437
      consecutive, symptomatic patients with neck pain with or without neurogenic
      symptoms were included in this study. MRI in multiple positions was performed
      with dynamic motion of the cervical spine in upright, weight-bearing neutral,
      flexion and extension positions. Type of MC, intervertebral disc degeneration
      grade, spinal cord compression grade and sagittal angular motion between flexion
      and extension for each segment from C2-3 to C6-7 were evaluated. RESULTS: MCs
      were observed in 84 out of 437 patients (19.2%) and in 109 out of 2,185 motion
      segments (5.0%) with type 2 changes predominating. Disc degeneration grades and
      spinal cord compression grades of segments with MCs were significantly higher
      than those without MCs. Sagittal angular motion of segments with MCs were
      significantly lower than those without MCs. Multiple logistic regression analysis
      revealed that significantly elevated odds ratios for MCs were observed in
      segments with severe disc degeneration, severe spinal canal compression and less
      angular motion. CONCLUSION: The cervical segments with MCs were significantly
      more likely to have disc degeneration and spinal canal stenosis. In addition, the
      segments with MCs had significantly less angular motion, which suggests MCs may
      correlate with loss of mobility.

PMID- 24913215
TI  - [Removal due to cut-out effect in pertrochanteric femoral fractures: what is the
      rescue treatment of choice?].
AB  - OBJECTIVE: The goal of the study was to compare functional results in different
      treament options in cutting-out, and analize factors associated to failure.
      MATERIAL AND METHODS: Retrospective cohort study in 56 patients diagnosed with
      cutting-out between 2000-2010. Groups were based on rescue treatment:
      arthroplasty versus alternative treatment. Demographics, fracture
      characteristics, osteosynthesis, tip to apex distance (TAD), follow-up,
      complications, and final functional capacity were analyzed. RESULTS: Rescue
      treatment: 36 (64.28%) hip replacement (arthroplasty group), and 20 (35.72%)
      alternative treatment preserving femoral head (alternative group). Groups
      comparable on demographic parameters, fracture pattern and osteosynthesis
      characteristics. Radiography analysis: low inter-observer variability (k=0.83,
      95% CI 0.78-0.88), mean TAD 28.66mm (arthroplasty group 32.9mm, 21.5mm control
      group; p=0.01), insufficient fracture reduction 39.3% (p=0.001). Cutting-out
      diagnosis median 60 days (arthroplasty group 90 days, 18 days alternative group;
      p=0.001). Follow up at least 12 months from rescue treatment. Similar
      complications rate in both groups (p=0.16). Re-operation rate 3.57% (11.7%
      arthroplasty group, alternative group 0%; p=0.01). Better final functional
      capacity in arthroplasty group (p=0.004). DISCUSSION: Hip arthroplasty offers
      better results, being considered the gold standard in geriatric patients,
      although re-operation rate is higher. We recommend new nailing before
      arthroplasty in early failure (4 weeks) in patients with femoral head integrity.
      An insufficient fracture reduction is the main short term factor predicting
      failure; and TAD higher than 20mm is a middle-long term one.

PMID- 24913216
TI  - [Proximal interphalangeal joint replacement: A comparison between the volar and
      dorsal approach].
AB  - INTRODUCTION: Arthropathy of the proximal interphalangeal (PIP) joint symptoms is
      very restrictive, and in some cases arthroplasty is required. In most of the
      reported series of PIP silicone arthroplasty, the technique described is the
      dorsal approach. As far as we know, the role of the volar approach in PIP
      arthroplasty has still not been adequately assessed. OBJECTIVES: To
      retrospectively review the patients who had PIP joint arthroplasty, and to study
      the clinical and radiographic outcomes in relation to the approach: volar or
      dorsal. METHODS: A total of 22 PIP joint replacements were performed between 2005
      and 2010. The mean age was 56 years and the mean follow-up period was 29 months.
      The implant used in all patients was the Avanta(r) PIP Soft-Skeletal Implant
      (Avanta Orthopaedics, San Diego, USA). The dorsal approach was performed in 14
      joints, and a volar approach in 8 joints. The preoperative clinical evaluation
      included a visual analogue scale (VAS) and the range of motion (ROM). The
      preoperative ROM mean was -15 degrees /60 degrees  in both groups. The VAS and
      the ROM in the last follow-up visit were recorded and compared with preoperative
      values. RESULTS: The postoperative ROM of the dorsal approach group had a mean of
      -15 degrees /60 degrees , and that of the volar approach was -2 degrees /62
      degrees . CONCLUSION: It was found that the volar approach in this series offers
      the advantages of maintaining the integrity of the extensor mechanism, resulting
      in a complete restoration of the extension in the range of motion.

PMID- 24913217
TI  - Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel
      disease via a PXR-dependent pathway.
AB  - Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We
      recently reported the identification of isorhamnetin as an activator of the human
      pregnane X receptor (PXR), a known target for abrogating inflammation in
      inflammatory bowel disease (IBD). The current study investigated the role of
      isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced
      IBD. Using two different models (ulcerative colitis like and Crohn's disease
      like) of experimental IBD in mice, we demonstrated that isorhamnetin abrogated
      inflammation through inhibiting the activity of myeloperoxidase, the levels of
      TNF-alpha and IL-6, the mRNA expression of proinflammatory mediators (iNOS, ICAM
      1, COX2, TNF-alpha, IL-2 and IL-6) and the phosphorylation of IkappaBalpha and NF
      kappaB p65. PXR gene overexpression inhibited NF-kappaB luciferase activity, and
      the inhibition was potentiated by isorhamnetin treatment. PXR knockdown by siRNA
      demonstrated the necessity for PXR in isorhamnetin-mediated up-regulation of
      xenobiotic metabolism genes. Ligand pocket-filling mutants (S247W/C284W and
      S247W/C284W/S208W) of human PXR weakened the effect of isorhamnetin on PXR
      activation. Molecular docking studies and time-resolved fluorescence resonance
      energy transfer competitive binding assays confirmed the ligand (isorhamnetin)
      binding affinity. These results clearly demonstrated the ameliorating effect of
      isorhamnetin on experimental IBD via PXR-mediated up-regulation of xenobiotic
      metabolism and down-regulation of NF-kappaB signaling. The novel findings may
      contribute to the effective utilization of isorhamnetin or its derivatives as a
      PXR ligand in the treatment of human IBD.

PMID- 24913218
TI  - An evaluation of the potential drug interaction between warfarin and
      levothyroxine.
AB  - BACKGROUND: Drug interaction references report that initiation of levothyroxine
      potentiates the effects of warfarin, and recommend more frequent International
      Normalized Ratio (INR) monitoring, but the mechanism is not well understood.
      OBJECTIVE: To assess the impact of levothyroxine initiation on INR response.
      PATIENTS/METHODS: A retrospective, self-controlled study was performed on
      patients aged >= 18 years receiving chronic warfarin therapy who were started on
      levothyroxine between 1 January 2006 and 30 June 2013, and who were followed for
      90 days prior to and after levothyroxine initiation. The included patients had at
      least one elevated thyroid-stimulating hormone laboratory value in the pre
      period, continuous warfarin therapy for 100 days prior to levothyroxine
      initiation, no purchases of medications known to interact with warfarin, no
      procedures requiring warfarin interruption, and no bleeding or thromboembolic
      event during the study period. The primary outcome was a comparison of the
      warfarin dose/INR ratio recorded before the initiation of levothyroxine with the
      ratio recorded during the post-period after two consecutive INRs with no warfarin
      dose change. RESULTS: One hundred and two patients were included in the primary
      outcome. The mean warfarin dose/INR ratios in the pre-period and post-period were
      equivalent (P = 0.825). Although the mean warfarin dose was numerically lower in
      the post-period than in the pre-period, this difference did not reach statistical
      significance (P = 0.068). CONCLUSION: No difference in the mean warfarin dose/INR
      ratio before and after initiation of levothyroxine was detected. The results
      suggest that there is not a clinically significant interaction between warfarin
      and levothyroxine, and so additional monitoring may not be necessary.

PMID- 24913219
TI  - Exercise training in adults with CKD: a systematic review and meta-analysis.
AB  - BACKGROUND: Whether exercise can affect health outcomes in people with chronic
      kidney disease (CKD) and what the optimal exercise strategies are for patients
      with CKD remain uncertain. STUDY DESIGN: Systematic review and meta-analysis of
      randomized controlled trials. SETTING & POPULATION: Adults with CKD stages 2-5,
      dialysis therapy, or a kidney transplant. SELECTION CRITERIA FOR STUDIES: Trials
      evaluating regular exercise training outcomes identified by searches in Cochrane
      CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science, BIOSIS, PEDro, AMED, AgeLine,
      PsycINFO, and KoreaMed, without language restriction. INTERVENTION: Regular
      exercise training for at least 8 weeks. OUTCOMES: Vary by study but could include
      aerobic capacity, muscular functioning, cardiovascular function, walking
      capacity, and health-related quality of life. Treatment effects were summarized
      as standardized difference with 95% CIs using random-effects meta-analysis.
      RESULTS: 41 trials (928 participants) comparing exercise training with sham
      exercise or no exercise were included; overall, improved aerobic capacity,
      muscular functioning, cardiovascular function, walking capacity, and health
      related quality of life were associated with various exercise interventions,
      although the preponderance of data were for dialysis patients and used aerobic
      exercise programs. LIMITATIONS: Unclear or high risk of bias in 32% of the
      trials, few trial data concerning resistance training, and limited data for
      several important outcomes. CONCLUSIONS: Regular exercise training generally is
      associated with improved health outcomes in individuals with CKD. Correctly
      designed exercise rehabilitation may be an effective part of care for adults with
      CKD. Future studies should examine longer term outcomes and strategies to
      translate exercise done in a supervised setting to the home setting for broader
      applicability.

PMID- 24913220
TI  - A randomized trial of Text2Quit: a text messaging program for smoking cessation.
AB  - BACKGROUND: Text messaging programs on mobile phones have shown some promise in
      helping people quit smoking. Text2Quit is an automated, personalized, interactive
      mobile health program that sends text messages to offer advice, support, and
      reminders about quitting smoking. PURPOSE: To evaluate the effect of Text2Quit on
      biochemically confirmed repeated point prevalence abstinence in the context of an
      RCT conducted in the U.S. METHODS: Participants (n=503) were recruited on the
      Internet and randomized to receive Text2Quit or self-help material. Between 2011
      and 2013, participants were surveyed at baseline and at 1, 3, and 6 months post
      enrollment to assess smoking status. Saliva was collected from participants who
      reported not smoking in the past 7 days at the 6-month follow-up. An intent to
      treat analysis was used, and those lost to follow-up were categorized as smokers.
      All analyses were completed in 2013. RESULTS: Biochemically confirmed repeated
      point prevalence abstinence favored the intervention group, with 11.1% abstinent
      compared to 5.0% of the control group (relative risk=2.22, 95% CI=1.16, 4.26,
      p<0.05). Similarly, self-reported repeated point prevalence abstinence was higher
      in the intervention group (19.9%) than in the control group (10.0%) (p<0.01).
      Effects were found to be uniform across the analyzed demographic subgroups,
      although suggestive of a larger effect for non-whites than whites. CONCLUSIONS:
      These results provide initial support for the relative efficacy of the Text2Quit
      program.

PMID- 24913222
TI  - Global warming and altitude malaria.

PMID- 24913221
TI  - US Senate confirms Burwell as secretary of health.

PMID- 24913225
TI  - The N-terminal of annexin A1 as a secondary membrane binding site: a molecular
      dynamics study.
AB  - Annexin A1 has been shown to cause membrane aggregation and fusion, yet the
      mechanism of these activities is not clearly understood. In this work, molecular
      dynamics simulations were performed on monomeric annexin A1 positioned between
      two negatively charged monolayers using AMBER's all atom force field to gain
      insight into the mechanism of fusion. Each phospolipid monolayer was made up of
      180 DOPC molecules and 45 DOPG molecules to achieve a 4:1 ratio. The space
      between the two monolayers was explicitly solvated using TIP3P waters in a
      rectilinear box. The constructed setup contained up to 0.14 million atoms.
      Application of periodic boundary conditions to the simulation setup gave the
      desired effect of two continuous membrane bilayers. Nonbonded interactions were
      calculated between the N-terminal residues and the bottom layer of phospholipids,
      which displayed a strong attraction of K26 and K29 to the lipid head-groups. The
      side-chains of these two residues were observed to orient themselves in close
      proximity (~3.5 A) with the polar head-groups of the phospholipids.

PMID- 24913227
TI  - Editorial: Suicide notes.

PMID- 24913223
TI  - Respiratory disease in United States farmers.
AB  - OBJECTIVES: Farmers may be at increased risk for adverse respiratory outcomes
      compared with the general population due to their regular exposures to dusts,
      animals and chemicals. However, early life farm exposures to microbial agents may
      result in reduced risk. Understanding respiratory disease risk among farmers and
      identifying differences between farmers and other populations may lead to better
      understanding of the contribution of environmental exposures to respiratory
      disease risk in the general population. METHODS: We compared the prevalence of
      self-reported respiratory outcomes in 43548 participants from the Agricultural
      Health Study (AHS), a prospective cohort of farmers and their spouses from Iowa
      and North Carolina, with data from adult participants in the National Health and
      Nutrition Examination Survey (NHANES) over the same period (2005-2010). RESULTS:
      AHS participants had lower prevalences of respiratory diseases (asthma, adult
      onset asthma, chronic bronchitis and emphysema), but higher prevalences of
      current respiratory symptoms (wheeze, cough and phlegm) even after controlling
      for smoking, body mass index and population characteristics. The overall
      prevalence of asthma in the AHS (7.2%, 95% CI 6.9 to 7.4) was 52% of that in
      NHANES (13.8%, 95% CI 13.3 to 14.3), although the prevalence of adult-onset
      asthma among men did not differ (3.6% for AHS, 3.7% for NHANES). Conversely, many
      respiratory symptoms were more common in the AHS than NHANES, particularly among
      men. CONCLUSIONS: These findings suggest that farmers and their spouses have
      lower risk for adult-onset respiratory diseases compared with the general
      population, and potentially higher respiratory irritation as evidenced by
      increased respiratory symptoms.

PMID- 24913228
TI  - Assisted suicide guidelines - 3 years on.

PMID- 24913229
TI  - Cancer: Where were we, where are we, where are we going.
AB  - Cancer diagnosis, medicine, prevention and care is changing - all for the better.
      As opposed to the "old days" of luck, trial and error and toxicity, we are now
      entering a new dawn due to advances in genomics and our understanding of biology.
      Personalised medicine or PM (aspects of which may also be referred to as
      precision medicine) is a medical model that proposes the customisation of
      healthcare - with medical decisions, practices, and/or products being tailored to
      the individual patient. This talk examines how this has evolved in the field of
      oncology, to maximise benefits to our patients and minimise toxicity, being able
      to predict in advance who our therapies will work for.

PMID- 24913230
TI  - Expert psychiatric evidence.

PMID- 24913231
TI  - DOCK5 functions as a key signaling adaptor that links FcepsilonRI signals to
      microtubule dynamics during mast cell degranulation.
AB  - Mast cells play a key role in the induction of anaphylaxis, a life-threatening
      IgE-dependent allergic reaction, by secreting chemical mediators that are stored
      in secretory granules. Degranulation of mast cells is triggered by aggregation of
      the high-affinity IgE receptor, FcepsilonRI, and involves dynamic rearrangement
      of microtubules. Although much is known about proximal signals downstream of
      FcepsilonRI, the distal signaling events controlling microtubule dynamics remain
      elusive. Here we report that DOCK5, an atypical guanine nucleotide exchange
      factor (GEF) for Rac, is essential for mast cell degranulation. As such, we found
      that DOCK5-deficient mice exhibit resistance to systemic and cutaneous
      anaphylaxis. The Rac GEF activity of DOCK5 is surprisingly not required for mast
      cell degranulation. Instead, DOCK5 associated with Nck2 and Akt to regulate
      microtubule dynamics through phosphorylation and inactivation of GSK3beta. When
      DOCK5-Nck2-Akt interactions were disrupted, microtubule formation and
      degranulation response were severely impaired. Our results thus identify DOCK5 as
      a key signaling adaptor that orchestrates remodeling of the microtubule network
      essential for mast cell degranulation.

PMID- 24913232
TI  - Neutrophils recruited by chemoattractants in vivo induce microvascular plasma
      protein leakage through secretion of TNF.
AB  - Microvascular plasma protein leakage is an essential component of the
      inflammatory response and serves an important function in local host defense and
      tissue repair. Mediators such as histamine and bradykinin act directly on venules
      to increase the permeability of endothelial cell (EC) junctions. Neutrophil
      chemoattractants also induce leakage, a response that is dependent on neutrophil
      adhesion to ECs, but the underlying mechanism has proved elusive. Through
      application of confocal intravital microscopy to the mouse cremaster muscle, we
      show that neutrophils responding to chemoattractants release TNF when in close
      proximity of EC junctions. In vitro, neutrophils adherent to ICAM-1 or ICAM-2
      rapidly released TNF in response to LTB4, C5a, and KC. Further, in TNFR(-/-)
      mice, neutrophils accumulated normally in response to chemoattractants
      administered to the cremaster muscle or dorsal skin, but neutrophil-dependent
      plasma protein leakage was abolished. Similar results were obtained in chimeric
      mice deficient in leukocyte TNF. A locally injected TNF blocking antibody was
      also able to inhibit neutrophil-dependent plasma leakage, but had no effect on
      the response induced by bradykinin. The results suggest that TNF mediates
      neutrophil-dependent microvascular leakage. This mechanism may contribute to the
      effects of TNF inhibitors in inflammatory diseases and indicates possible
      applications in life-threatening acute edema.

PMID- 24913233
TI  - Frequent disruption of the RB pathway in indolent follicular lymphoma suggests a
      new combination therapy.
AB  - Loss of cell cycle controls is a hallmark of cancer and has a well-established
      role in aggressive B cell malignancies. However, the role of such lesions in
      indolent follicular lymphoma (FL) is unclear and individual lesions have been
      observed with low frequency. By analyzing genomic data from two large cohorts of
      indolent FLs, we identify a pattern of mutually exclusive (P = 0.003) genomic
      lesions that impair the retinoblastoma (RB) pathway in nearly 50% of FLs. These
      alterations include homozygous and heterozygous deletions of the p16/CDKN2a/b
      (7%) and RB1 (12%) loci, and more frequent gains of chromosome 12 that include
      CDK4 (29%). These aberrations are associated with high-risk disease by the FL
      prognostic index (FLIPI), and studies in a murine FL model confirm their
      pathogenic role in indolent FL. Increased CDK4 kinase activity toward RB1 is
      readily measured in tumor samples and indicates an opportunity for CDK4
      inhibition. We find that dual CDK4 and BCL2 inhibitor treatment is safe and
      effective against available models of FL. In summary, frequent RB pathway lesions
      in indolent, high-risk FLs indicate an untapped therapeutic opportunity.

PMID- 24913234
TI  - Innate lymphoid cells facilitate NK cell development through a lymphotoxin
      mediated stromal microenvironment.
AB  - Natural killer (NK) cell development relies on signals provided from the bone
      marrow (BM) microenvironment. It is thought that lymphotoxin (LT) alpha1beta2
      expressed by the NK cell lineage interacts with BM stromal cells to promote NK
      cell development. However, we now report that a small number of RORgammat(+)
      innate lymphoid cells (ILCs), and not CD3(-)NK1.1(+) cells, express LT to drive
      NK development. Similar to LT(-/-) or RORgammat(-/-) mice, the mice conditionally
      lacking LTalpha1beta2 on RORgammat(+) ILCs experience a developmental arrest at
      the immature NK stages, between stages of NK development to the mature NK cell
      stage. This developmental block results in a functional deficiency in the
      clearance of NK-sensitive tumor cells. Reconstitution of Thy1(+) ILCs from BM or
      purified RORgammat(+) ILCs from lamina propria lymphocytes into LT-deficient
      RORgammat(+) BM cultures rescues NK cell development. These data highlight a
      previously undiscovered role of RORgammat(+) ILCs for NK cell development and
      define LT from ILCs as an essential molecule for the stromal microenvironment
      supporting NK cell development.

PMID- 24913235
TI  - Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell
      retention in germinal centers.
AB  - Follicular helper T (Tfh) cells access the B cell follicle to promote antibody
      responses and are particularly important for germinal center (GC) reactions.
      However, the molecular mechanisms of how Tfh cells are physically associated with
      GCs are incompletely understood. We report that the sphingosine-1-phosphate
      receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that
      localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs
      due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were
      ineffective in supporting GC responses compared with T cells deficient only in
      CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate
      localization of Tfh cells in GCs to support GC responses.

PMID- 24913236
TI  - Analysis of binding interaction between antibacterial ciprofloxacin and human
      serum albumin by spectroscopic techniques.
AB  - The binding of ciprofloxacin (CFX) to human serum albumin (HSA) has been
      investigated by fluorescence displacement and induced circular dichroism (ICD)
      measurements. Displacement measurements were performed with CFX in the absence
      and presence of marker ligands (hemin for domain I, bilirubin for interspace of
      domain IA and IIA, chloroform for domain II, and diazepam for domain III) to
      establish CFX binding site in one of the three major domains of HSA. The primary
      binding site of CFX is located in site I of HSA (domain IIA) in close vicinity to
      the site where chloroform (CHCl3) binds. It is depicted from the decrease in
      quenching constant of HSA-CHCl3 system (0.02 +/- 0.06) * 10(-3 )L mol(-1)
      compared to HSA-CFX-CHCl3 system (0.01 +/- 0.06) * 10(-3 )L mol(-1) as obtained
      by the fluorescence displacement spectroscopy. Furthermore, far-UV CD results
      show that the binding of CFX leads to change in the helicity of HSA. The ICD
      results indicated that the CFX binds to the domain IIA of HSA which is in
      agreement with the fluorescence displacement results.

PMID- 24913237
TI  - Low-grade inflammation in overweight and obese adults is affected by weight loss
      program.
AB  - PURPOSE: Low-grade systemic inflammation due to obesity is considered to be the
      key link between obesity and obesity-related disorders. The hypothesis was tested
      that significant alterations in inflammatory markers and adipokines would occur
      over a multidisciplinary intervention and that these changes might also be
      important for improvement of cardiovascular risk factors. METHODS: Thirty-tree
      overweight adults completed a 6-month multidisciplinary intervention program to
      evaluate the effects of a personalized dietary program based on the individual's
      resting metabolic rate (RMR) on anthropometric parameters, aerobic and anaerobic
      capabilities, metabolic profile, inflammation, and body image satisfaction. Body
      composition, physical activity, anaerobic capabilities, RMR, metabolic profile,
      and low-grade inflammation were measured. Diet composition and body image
      dissatisfaction were also assessed. RESULTS: After 6 months of multidisciplinary
      intervention the participants showed significantly decreased body weight, waist
      circumference (WC), and the inflammatory markers tumor necrosis factor-alpha, C
      reactive protein, and visfatin. They also showed increased anti-inflammatory
      adiponectin and consequently decreased serum insulin, HOMA-IR, and total
      cholesterol. The important findings of the study were that reduction of sugars
      and saturated fatty acids in the diet, coupled with an increase in exercise,
      significantly correlated with reduction of WC and body mass index. In addition,
      positive correlations between ? BMI, ? WC, ? trunk fat, inflammation, and
      cardiovascular risk factors were demonstrated. CONCLUSIONS: Weight loss in
      combination with increased physical activity, a negative energy balance, and diet
      adjustment was associated with lower inflammation and consequently with lower
      cardiovascular risk factors.

PMID- 24913239
TI  - Weight loss associated with bariatric surgery does not restore short telomere
      length of severe obese patients after 1 year.
AB  - BACKGROUND: Telomere shortening is physiologically associated with ageing but it
      may be influenced by oxidative stress and chronic inflammation, linked to
      obesity. Thus, obesity might represent an additional cause of telomere attrition.
      We aim to study relative telomere length (RTL) in obese subjects with and without
      metabolic syndrome and to assess the effect of weight loss induced by bariatric
      surgery. METHODS: We evaluated RTL in 107 obese subjects (62 with metabolic
      syndrome and 45 without metabolic syndrome), compared to 130 age-matched non
      obese subjects. We also measured RTL in a subgroup of 93 obese patients prior to
      and 3, 6, 9 and 12 months after surgery. RESULTS: RTL of obese subjects was
      significantly shorter (p<0.0001) than non-obese subjects but without differences
      between patients with and without metabolic syndrome (p=0.19). RTL was
      significantly shorter than baseline at 3, 6, 9 and 12 months after bariatric
      surgery. CONCLUSIONS: These results confirm that obese subjects have shorter
      telomeres compared to non-obese subjects, but RTL is not influenced by the
      presence of metabolic syndrome. RTL shows an additional attrition during the
      immediate post-operative period, probably due to a catabolic state.

PMID- 24913238
TI  - Extrathyroidal manifestations of Graves' disease: a 2014 update.
AB  - INTRODUCTION: Graves' orbitopathy (GO), thyroid dermopathy (also called pretibial
      myxedema) and acropachy are the extrathyroidal manifestations of Graves' disease.
      They occur in 25, 1.5, and 0.3 % of Graves' patients, respectively. Thus, GO is
      the main and most common extrathyroidal manifestation. Dermopathy is usually
      present if the patient is also affected with GO. The very rare acropachy occurs
      only in patients who also have dermopathy. GO and dermopathy have an autoimmune
      origin and are probably triggered by autoimmunity to the TSH receptor and,
      likely, the IGF-1 receptor. Both GO and dermopathy may be mild to severe.
      MANAGEMENT: Mild GO usually does not require any treatment except for local
      measures and preventive actions (especially refraining from smoking). Currently,
      moderate-to-severe and active GO is best treated by systemic glucocorticoids, but
      response to treatment is not optimal in many instances, and retreatments and use
      of other modalities (glucocorticoids, orbital radiotherapy, cyclosporine) and, in
      the end, rehabilitative surgery are often needed. Dermopathy is usually managed
      by local glucocorticoid treatment. No specific treatment is available for
      acropachy. PERSPECTIVES: Novel treatments are presently being investigated for
      GO, and particular attention is paid to the use of rituximab. It is unknown
      whether novel treatments for GO might be useful for the other extrathyroidal
      manifestations. Future novel therapies shown to be beneficial for GO in
      randomized studies may be empirically used for dermopathy and acropachy.

PMID- 24913240
TI  - A meta-analysis of 2-year effect after surgery: laparoscopic Roux-en-Y gastric
      bypass versus laparoscopic sleeve gastrectomy for morbid obesity and diabetes
      mellitus.
AB  - Literature search was performed for bariatric surgery from inception to September
      2013, in which the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) and
      laparoscopic sleeve gastrectomy (LSG) on body mass index (BMI), percentage of
      excess weight loss (EWL%), and diabetes mellitus (DM) were compared 2 years post
      surgery. A total of 9,756 cases of bariatric surgery from 16 studies were
      analyzed. Patients receiving LRYGB had significantly lower BMI and higher EWL%
      compared with those receiving LSG (BMI mean difference (MD) = -1.38, 95%
      confidence interval (CI) = -1.72 to -1.03; EWL% MD = 5.06, 95% CI = 0.24 to
      9.89). Improvement rate of DM was of no difference between the two types of
      bariatric surgeries (RR = 1.05, 95% CI = 0.90 to 1.23). LRYGB had better long
      term effect on body weight, while both LRYGB and LSG showed similar effects on
      DM.

PMID- 24913241
TI  - Cost-utility analysis of gastric bypass for severely obese patients in Spain.
AB  - BACKGROUND: To assess the cost-utility of gastric bypass versus usual care for
      patients with severe obesity in Spain. METHODS: We have implemented a discrete
      event simulation model with two branches: one branch involves gastric bypass,
      thereby reducing patients' BMI, and another branch where patients do not undergo
      surgery. The model analyzes the emergence of comorbidities (stroke, coronary
      obstructive disease, diabetes, and breast cancer) associated with obesity during
      a lifetime horizon. The selected measure of effectiveness is health-related
      quality of life. Both costs and effects are discounted at 3 %. A probabilistic
      sensitivity analysis is also performed using second-order Monte Carlo simulation;
      acceptability curves for different time horizons were also calculated. RESULTS:
      Patients with gastric bypass result in a lifetime increase of 5.63 quality
      adjusted life years (QALYs) (18.18 vs. 12.55 QALYs). In addition, because of the
      reduced spending associated with the treatment of various obesity-related
      comorbidities, final savings stand at 13,994 <euro>. The total cost of the
      intervention branch is close to half the cost of the non-intervention branch
      (17,431 vs. 31,425 <euro>). CONCLUSIONS: Gastric bypass is an intervention that
      dominates over the option of not intervening when a lifetime horizon is
      considered.

PMID- 24913242
TI  - Does epidural morphine loading in addition to thoracic epidural analgesia benefit
      the postoperative management of morbidly obese patients undergoing open bariatric
      surgery? A pilot study.
AB  - BACKGROUND: Insufficient data exist regarding postoperative thoracic epidural
      analgesia for morbidly obese patients undergoing open bariatric surgery. This
      study evaluated the effectiveness of morphine loading in a postoperative thoracic
      epidural analgesic regimen of patient-controlled epidural analgesia (PCEA) with
      levobupivacaine combined with continuously administered epidural morphine in this
      patient group. METHODS: In this prospective randomized controlled trial, 48
      superobese patients (body mass index of >= 50 kg/m(2)) undergoing open bariatric
      surgery were randomly allocated to three groups of 16 patients each.
      Postoperatively, all groups received a continuous epidural morphine infusion of
      0.2 mg/h with 0.1 % levobupivacaine via PCEA. Group A did not receive
      intraoperative epidural morphine loading, while groups B and C received an
      intraoperative 1- and 2-mg morphine bolus, respectively. Levobupivacaine
      consumption via PCEA (primary outcome), pain scores at rest and on cough, the
      time to return of bowel function and ambulation, and arterial blood gas levels
      (secondary outcomes) were recorded. RESULTS: The increase in perioperative
      morphine administration (groups B and C) led to a significantly prolonged return
      to normal bowel function and delayed ambulation (P<0.05 to 0.01, respectively),
      without an improvement in postoperative analgesia or a reduction in local
      anesthetic consumption. Although the prevalence of obstructive sleep apnea (OSA)
      was high in all groups, no respiratory depression was observed. CONCLUSIONS:
      Thoracic PCEA with 0.1 % levobupivacaine combined with continuous epidural
      morphine administration of 0.2 mg/h without morphine loading is an effective
      postoperative analgesic regimen that provides adequate pain control, early
      ambulation, and early return of bowel function in superobese patients,
      particularly those with OSA.

PMID- 24913244
TI  - Assessing marijuana use in bariatric surgery candidates: should it be a
      contraindication?
AB  - Research has demonstrated negative effects of both alcohol and tobacco use after
      bariatric surgery. However, no research to date has examined effects of cannabis
      use after bariatric surgery, even though cannabis is the most commonly used
      illicit drug in the USA. Literature review reveals that many practitioners
      generalize from data regarding alcohol abuse to all substances. Further, many
      screening protocols fail to differentiate between varying levels of cannabis use.
      The current report aims to (1) review the relevant literature on marijuana use
      and its potential consequences among bariatric patients, (2) discuss relevant
      problems and gaps in this literature, and (3) make preliminary recommendations
      regarding the assessment and treatment planning of bariatric candidates who
      disclose marijuana use. 

PMID- 24913245
TI  - The Effectiveness of the Tupiq Program for Inuit Sex Offenders.
AB  - This study examines the effectiveness of the Tupiq program, a culturally specific
      program for Inuit sex offenders that incorporates cognitive behavioural methods
      with traditional Inuit knowledge and culture led by Inuit healers and
      facilitators. Outcomes of 61 offenders who participated in the Tupiq program and
      were released were compared with outcomes of a cohort of 114 released Inuit sex
      offenders incarcerated during the same time period who had taken alternative sex
      offender treatment programs, or had not attended any sex offender program. On
      release, Tupiq participants had significantly lower rates of general reoffending
      and violent reoffending than those in the combined comparison group. The hazard
      of reoffending for the comparison group was almost twice that of the Tupiq group.
      Although the sexual reoffending rate for the Tupiq participants was less than
      half of that of the comparison group, the difference between the two groups was
      not significant because of reduced statistical power. Survival analysis
      controlling for covariates confirmed significantly lower rates of general
      reoffending for the Tupiq group. Further analyses comparing the outcomes of the
      subgroup of offenders in the comparison group who participated in alternative sex
      offender treatment programs with those who participated in Tupiq indicated that
      Tupiq participants had significantly lower rates of both general and sexual
      reoffending. These positive results for this culturally specific program suggest
      that similarly designed interventions have a probability of contributing to the
      reduction of sexual offending within Inuit communities and, potentially, other
      jurisdictions that work with cultural minority sex offender groups from
      relatively isolated communities. 

PMID- 24913243
TI  - Quality of life, weight loss and improvement of co-morbidities after primary and
      revisional laparoscopic roux Y gastric bypass procedure-comparative match pair
      study.
AB  - BACKGROUND: The prevalence of morbid obesity and its co-morbidities is
      dramatically increasing, as is the extent of weight loss surgery. A large number
      of patients after various bariatric procedures need revisional intervention for
      various reasons. We investigated the efficacy and the safety of revisional
      laparoscopic Roux Y gastric bypass (LRYGB) among our patients, who were revised
      as a consequence of inadequate weight loss or weight regain after previous
      bariatric interventions. METHODS: A comparative, double-centre, match pair study
      was performed comparing the data of 44 patients after revisional surgery with 44
      patients after primary gastric bypasses, focusing on weight loss, life quality
      and improvement of co-morbidities. Matching criteria were age, gender,
      preoperative BMI and follow-up period. Previous procedures consisted of 23
      gastric bandings, 13 sleeve resections, 4 LRYGB and 4 vertical banded
      gastroplasties. RESULTS: Extra weight loss (EWL) was significantly reduced after
      revisional gastric bypasses compared to primary intervention (EWL 66 vs. 91 %,
      p<0.05). Life quality scores were also decreased in the revisional group compared
      to the control group without statistical significance (SF 36 score 635 vs. 698.5,
      p=0.22; Moorehead-Aldert II score 1.4 vs. 2.0, p=0.10). The resolution rate of co
      morbidities (T2DM, hypertension, gastro-oesophageal reflux (GER), osteoarthrosis,
      sleep apnoea) was also higher after primary gastric bypasses. CONCLUSIONS:
      Revisional LRYGB is an effective and safe method for patients with inadequate
      weight loss after previous bariatric surgery concerning weight reduction, life
      quality and improvement of co-morbidities. Our results indicate lower efficacy of
      revisional compared to primary LRYGB reaching statistical significance in regard
      to weight loss.

PMID- 24913246
TI  - Mycobacteriophage L5Gp56, a novel member of the NrdH family of redoxins.
AB  - Mycobacteriophage L5 gene 56 encodes a putative thioredoxin family protein.
      Phylogenetic analysis revealed that Gp56 and related proteins are distantly
      related to NrdH - a glutaredoxin homolog which has thioredoxin-like properties.
      To understand its function, the recombinant version of the protein was
      biochemically characterized. For the sake of comparison, a mycobacterial
      thioredoxin, TrxB, was included in the study. Results show that Gp56 can be
      reduced by dithiothreitol, but only at a higher concentration as compared with
      TrxB, indicating that the standard redox potential of Gp56 is lower than that of
      TrxB. The reduced protein can subsequently act as a reductant of protein
      disulfide bonds. Gp56 can be reduced by NADPH with the help of thioredoxin
      reductase (TrxR) but less efficiently as compared with TrxB. The abilities of
      Gp56 and TrxB to reduce Gp50, the L5-encoded ribonucleotide reductase, was
      examined. While both are capable of executing this function, the former needs
      more reducing equivalents in the process as compared with the latter. This study
      shows that L5Gp56 represents a new class of NrdH-like proteins that function
      optimally in a reducing environment.

PMID- 24913247
TI  - Ambulatory mental health data demonstrates the high needs of people with an
      intellectual disability: results from the New South Wales intellectual disability
      and mental health data linkage project.
AB  - OBJECTIVE: To investigate the ambulatory mental health service profile of persons
      with intellectual disability (ID) in a representative sample of New South Wales
      (NSW). METHODS: A statistical linkage key was used to link the Disability
      Services Minimum Data Set (DS-MDS) and a community mental health services dataset
      (MH-COM) for a representative area of NSW for the period 2005-2010. Linkage was
      undertaken in four NSW local health districts (LHDs), covering 36.7% of the NSW
      population. The mental health profiles and service use characteristics of people
      with an ID were compared to mental health service users without an ID. RESULTS:
      Of the 89,262 people in the MH-COM over this 6-year period, 1,459 people (1.6 %)
      were identified as having an ID. Compared to those without an ID, people with an
      ID were more likely to have psychotic disorders, developmental disorders and
      personality disorders, and more than twice as likely to have an 'unknown'
      diagnosis. Compared to those without an ID, people with an ID were less likely to
      have depressive disorders, adjustment disorders and other disorders. Service use
      profiles revealed that people with an ID had 1.6 times more face-to-face
      contacts, and a total face-to-face contact time which was 2.5 times longer than
      people without an ID. CONCLUSIONS: Ambulatory mental health data from NSW
      indicates that people with an ID receive care for a distinct range of mental
      disorders, and experience uncertainty regarding their diagnosis. People with an
      ID have higher service needs which require recognition and the allocation of
      specific resources. Such data provide a suitable baseline for future evaluation
      of the impact of ambulatory mental health reforms for people with an ID.

PMID- 24913249
TI  - How to deal with petabytes of data: the LHC Grid project.
AB  - We review the Grid computing system developed by the international community to
      deal with the petabytes of data coming from the Large Hadron Collider at CERN in
      Geneva with particular emphasis on the ATLAS experiment and the UK Grid project,
      GridPP. Although these developments were started over a decade ago, this article
      explains their continued relevance as part of the 'Big Data' problem and how the
      Grid has been forerunner of today's cloud computing. 

PMID- 24913248
TI  - Solid-phase extraction of plant thionins employing aluminum silicate based
      extraction columns.
AB  - Thionins belong to a family of cysteine-rich, low-molecular-weight (~5 KDa)
      biologically active proteins in the plant kingdom. They display a broad cellular
      toxicity against a wide range of organisms and eukaryotic cell lines. Thionins
      protect plants against different pathogens, including bacteria and fungi. A
      highly selective solid-phase extraction method for plant thionins is reported
      deploying aluminum silicate (3:2 mullite) powder as a sorbent in extraction
      columns. Mullite was shown to considerably improve selectivity compared to a
      previously described zirconium silicate embedded poly(styrene-co-divinylbenzene)
      monolithic polymer. Due to the presence of aluminum(III), mullite offers
      electrostatic interactions for the selective isolation of cysteine-rich proteins.
      In comparison to zirconium(IV) silicate, aluminum(III) silicate showed reduced
      interactions towards proteins which resulted into superior washings of unspecific
      compounds while still retaining cysteine-rich thionins. In the presented study,
      European mistletoe, wheat and barley samples were subjected to solid-phase
      extraction analysis for isolation of viscotoxins, purothionins and hordothionins,
      respectively. Matrix-assisted laser desorption/ionization time of flight mass
      spectroscopy was used for determining the selectivity of the sorbent toward
      thionins. The selectively retained thionins were quantified by colorimetric
      detection using the bicinchoninic acid assay. For peptide mass-fingerprint
      analysis tryptic digests of eluates were examined. 

PMID- 24913250
TI  - Functional variation in sensitivity to cues that a partner is cheating with a
      rival.
AB  - The costs imposed by a romantic partner's mixed reproductive strategy (MRS)
      generate selection pressures for anticipatory responses to mitigate or avoid
      those costs. People will differ in their vulnerability to those costs, based in
      part on the qualities of their romantic rivals. Thus, we predicted that
      individuals at high risk of a partner's MRS--women with many sexually accessible
      rivals and men with many rivals more physically attractive than themselves--would
      be more attentive to cues that an MRS was being employed than those at lower
      risk. Based on similarity judgments derived from a successive-pile-sort method,
      this prediction was supported in a study involving over 1,300 students and
      community members. These results complement a growing body of research on
      selection pressures generated by romantic rivals.

PMID- 24913251
TI  - Efficient energy transfer from inserted CdTe quantum dots to YVO4:Eu3+ inverse
      opals: a novel strategy to improve and expand visible excitation of rare earth
      ions.
AB  - Rare earth (RE)-based phosphors demonstrate sharp emission lines, long lifetimes
      and high luminescence quantum yields; thus, they have been employed in various
      photoelectric devices, such as light-emitting diodes (LEDs) and solar spectral
      converters. However, their applications are largely confined by their narrow
      excitation bands and small absorption cross sections of 4f-4f transitions. In
      this paper, we demonstrate a novel strategy to improve and expand the visible
      excitation bands of Eu(3+) ions through the interface energy transfer (ET) from
      CdTe quantum dots (QDs) to YVO4:Eu(3+) inverse opal photonic crystals (IOPCs).
      The significant effects observed in the CdTe QDs/YVO4:Eu(3+) IOPCs composites
      were that the excitation of Eu(3+) ions was continuously extended from 450 to 590
      nm and that the emission intensity of the (5)D0-(7)FJ transitions was enhanced
      ~20-fold, corresponding to the intrinsic (7)F1-(5)D1 excitation at 538 nm.
      Furthermore, in the IOPC network, the ET efficiency from the QDs to YVO4:Eu(3+)
      was greatly improved because of the suppression of energy migration among the
      CdTe QDs, which gave an optimum ET efficiency as high as 47%. Besides, the
      modulation of photonic stop bands (PSBs) on the radiative transition rates of the
      QDs and Eu(3+) ions was studied, which showed that the decay lifetime constants
      for Eu(3+) ions were independent of PSBs, while those of QDs demonstrated a
      suppression in the PSBs. Their physical nature was explained theoretically.

PMID- 24913252
TI  - Letter to the editor: Duodenal obstruction as the first symptom of the
      unrecognized breast carcinoma.

PMID- 24913253
TI  - Risk of comorbidities and outcomes in patients with lower gastrointestinal
      bleeding - a nationwide study.
AB  - BACKGROUND: The impact of comorbidities on outcomes of patients with lower
      gastrointestinal bleeding (LGIB) remains unknown. OBJECTIVE: Investigate the
      prevalence of comorbidities and impact on outcomes of patients with LGIB.
      METHODS: The Nationwide Inpatient Sample 2010 was used to identify patients who
      had a primary discharge diagnosis of LGIB based on International Classification
      of Diseases, the 9th revision, clinical modification codes. The presence of
      comorbid illness was assessed using the Elixhauser index. Logistic regression
      models were used to assess the contributions of the individual Elixhauser
      comorbidities to predict in-hospital mortality. RESULTS: A total of 58,296
      discharges with LGIB were identified. The overall mortality was 2.3 %. Among the
      patients who underwent colonoscopy, 17.3 % of patients had therapeutic
      intervention. As the number of comorbidities increased (i.e., 0, 1, 2, or >3),
      mortality increased (1.7, 2.0, 2.4, and 2.4 %, respectively). The mortality rate
      was highest in patients >65 years of age (2.7 %). Patients >65 years of age with
      two or more comorbidities had a mortality rate of 5 % as compared to 2.6 % in
      those with less than two comorbidities. Congestive heart failure (odds ratio,
      1.67 [95 % confidence interval, 1.48-1.95]), liver disease (2.64 [1.83-3.80]),
      renal failure (1.99 [1.70-2.33]), and weight loss (2.66 [2.27-3.12]) were
      associated with a significant increase in mortality rate. Comorbidities increased
      hospital stay and costs. CONCLUSIONS: Comorbidities were associated with
      increased the risk of mortality and health care utilization in patients with
      LGIB. Identification of comorbidities and development of risk-adjustment tools
      may improve the outcome of patients with LGIB.

PMID- 24913254
TI  - A comparison of the technical and oncologic validity between robot-assisted and
      conventional open abdominoperineal resection.
AB  - PURPOSE: This study was to ascertain whether a robot-assisted (RA) approach to
      APR might facilitate a cylindrical APR by enabling a deeper pelvic dissection
      during an abdominal approach, concurrently comparing the feasibility and short
      term oncologic outcomes. METHODS: Forty-eight consecutive patients with lower
      rectal cancer who had undergone curative APR (21 RA vs. 27 open) were
      prospectively enrolled. The short-term operative outcomes and oncologic
      feasibility were evaluated and compared. A levator muscle excision was performed
      concomitantly with the abdominal procedure in the RA group and with the perineal
      procedure in the open group. RESULTS: No patients in the RA group experienced
      intraoperative perforation or required conversion to open APR. Overall, a
      cylindrical APR was performed in 72 % of patients, and subtotal excision of the
      levator muscle, i.e., either one or both sides of the puborectalis and
      pubococcygeus muscles, was more likely in the RA group (P = 0.019). A positive
      CRM was exclusively identified in four open APR patients. The mean number of
      retrieved lymph nodes was greater in the RA group (20 vs. 16, P = 0.035). There
      was no difference in perineal morbidity between the two groups (P = 0.445).
      CONCLUSIONS: The RA approach facilitates an efficient excision in the pelvic
      region than open APR during the abdominal procedure. The RA approach also
      demonstrated a trend toward improved oncologic outcomes with equivalent
      postoperative morbidities than with the open approach.

PMID- 24913255
TI  - Oral anticoagulant agent-associated bleeding events reporting system (ORANGE)
      study.

PMID- 24913256
TI  - Assessing the environmental characteristics of cycling routes to school: a study
      on the reliability and validity of a Google Street View-based audit.
AB  - BACKGROUND: Google Street View provides a valuable and efficient alternative to
      observe the physical environment compared to on-site fieldwork. However, studies
      on the use, reliability and validity of Google Street View in a cycling-to-school
      context are lacking. We aimed to study the intra-, inter-rater reliability and
      criterion validity of EGA-Cycling (Environmental Google Street View Based Audit -
      Cycling to school), a newly developed audit using Google Street View to assess
      the physical environment along cycling routes to school. METHODS: Parents (n =
      52) of 11-to-12-year old Flemish children, who mostly cycled to school, completed
      a questionnaire and identified their child's cycling route to school on a street
      map. Fifty cycling routes of 11-to-12-year olds were identified and physical
      environmental characteristics along the identified routes were rated with EGA
      Cycling (5 subscales; 37 items), based on Google Street View. To assess
      reliability, two researchers performed the audit. Criterion validity of the audit
      was examined by comparing the ratings based on Google Street View with ratings
      through on-site assessments. RESULTS: Intra-rater reliability was high (kappa
      range 0.47-1.00). Large variations in the inter-rater reliability (kappa range 
      0.03-1.00) and criterion validity scores (kappa range -0.06-1.00) were reported,
      with acceptable inter-rater reliability values for 43% of all items and
      acceptable criterion validity for 54% of all items. CONCLUSIONS: EGA-Cycling can
      be used to assess physical environmental characteristics along cycling routes to
      school. However, to assess the micro-environment specifically related to cycling,
      on-site assessments have to be added.

PMID- 24913257
TI  - Fortification of rice: technologies and nutrients.
AB  - This article provides a comprehensive review of the currently available
      technologies for vitamin and mineral rice fortification. It covers currently used
      technologies, such as coating, dusting, and the various extrusion technologies,
      with the main focus being on cold, warm, and hot extrusion technologies,
      including process flow, required facilities, and sizes of operation. The
      advantages and disadvantages of the various processing methods are covered,
      including a discussion on micronutrients with respect to their technical
      feasibility during processing, storage, washing, and various cooking methods and
      their physiological importance. The microstructure of fortified rice kernels and
      their properties, such as visual appearance, sensory perception, and the impact
      of different micronutrient formulations, are discussed. Finally, the article
      covers recommendations for quality control and provides a summary of clinical
      trials. 

PMID- 24913258
TI  - A Sclerostin super-producer cell line derived from the human cell line SaOS-2: a
      new tool for the study of the molecular mechanisms driving Sclerostin expression.
AB  - Sclerostin, the product of the SOST gene, is a key regulator of bone homeostasis.
      Sclerostin interferes with the Wnt signalling pathway and, therefore, has a
      negative effect on bone formation. Although the importance of sclerostin in bone
      homeostasis is well established, many aspects of its biology are still unknown.
      Due to its restricted pattern of expression, in vitro studies of SOST gene
      regulation are technically challenging. Furthermore, a more profound
      investigation of the molecular mechanism controlling sclerostin expression has
      been hampered by the lack of a good human in vitro model. Here, we describe two
      cell lines derived from the human osteosarcoma cell line SaOS-2 that produce
      elevated levels of sclerostin. Analysis of the super-producer cell lines showed
      that sclerostin levels were still reduced in response to parathyroid hormone
      treatment or in response to mechanical loading, indicating that these regulatory
      mechanisms were not affected in the presented cell lines. In addition, we did not
      find differences between the promoter or ECR5 sequences of our clones and the
      SaOS-2 parental line. However, the methylation of the proximal CpG island located
      at the SOST promoter was lower in the super-producer clones, in agreement with a
      higher level of SOST transcription. Although the underlying biological causes of
      the elevated levels of sclerostin production in this cell line are not yet clear,
      we believe that it could be an extremely useful tool to study the molecular
      mechanisms driving sclerostin expression in humans. 

PMID- 24913259
TI  - Eight more people in UK sue Grunenthal and Diageo over thalidomide.

PMID- 24913260
TI  - Effective Brownian ratchet separation by a combination of molecular filtering and
      a self-spreading lipid bilayer system.
AB  - A new molecular manipulation method in the self-spreading lipid bilayer membrane
      by combining Brownian ratchet and molecular filtering effects is reported. The
      newly designed ratchet obstacle was developed to effectively separate dye-lipid
      molecules. The self-spreading lipid bilayer acted as both a molecular transport
      system and a manipulation medium. By controlling the size and shape of ratchet
      obstacles, we achieved a significant increase in the separation angle for dye
      lipid molecules compared to that with the previous ratchet obstacle. A clear
      difference was observed between the experimental results and the simple random
      walk simulation that takes into consideration only the geometrical effect of the
      ratchet obstacles. This difference was explained by considering an obstacle
      dependent local decrease in molecular diffusivity near the obstacles, known as
      the molecular filtering effect at nanospace. Our experimental findings open up a
      novel controlling factor in the Brownian ratchet manipulation that allow the
      efficient separation of molecules in the lipid bilayer based on the combination
      of Brownian ratchet and molecular filtering effects. 

PMID- 24913261
TI  - Single shot coherence properties of the free-electron laser SACLA in the hard X
      ray regime.
AB  - We measured the coherence properties of the free-electron laser SACLA on a single
      shot basis at an X-ray energy of 8 keV. By analysing small-angle X-ray scattering
      speckle patterns from colloidal dispersions we found a degree of transverse
      coherence of betat = 0.79 +/- 0.09. Taking detector properties into account, we
      developed a simulation model in oder to determine the degree of coherence from
      intensity histograms. Finally we calculated a coherence time of tauc = 0.1 fs and
      a pulse duration of 5.2 fs which corresponds with previous predictions.

PMID- 24913262
TI  - TMEM16A is a Ca(2+) -activated Cl(-) channel expressed in the renal collecting
      duct.
AB  - AIM: In the renal collecting ducts, ATP stimulates a Ca(2+) -activated chloride
      current. The identity of the channel responsible for the current under
      physiological conditions is not known and it was hypothesized that TMEM16a is a
      relevant candidate in the renal collecting duct. METHODS: The cortical collecting
      duct cell line M-1 was used as a model of the collecting duct. The ATP induced
      Ca(2+) signalling was imaged in cells loaded with Ca(2+) -sensitive fluorescent
      probes using confocal laser-scanning fluorescence microscopy. Chloride current
      was determined by mounting M-1 cell layers in Ussing chamber. The expression of
      TMEM16a in human kidney was tested by immunohistochemistry. RESULTS: M-1 cells
      displayed a transient increase in intracellular Ca(2+) concentration in response
      to 100 nm ATP. This response was completely blocked by addition of 100 MUm
      suramin, indicating that ATP signals through purinergic P2 receptors. Apical
      addition of 100 nm ATP induced a Cl(-) current, which was blocked by suramin, DPC
      and the cysteine-modifying compound MTSET. M-1 cells were found to express
      TMEM16a at the mRNA and protein level. Functionally, it was found that knock-down
      of TMEM16a expression in M-1 cells inhibited the ATP induced Cl(-) -current. In
      human and mouse kidney sections, TMEM16a protein expression was localized to the
      collecting duct, and TMEM16a was found to be excreted in human urinary exosomes.
      CONCLUSION: TMEM16a is a Ca(2+) -activated Cl(-) channel expressed in the
      collecting ducts.

PMID- 24913263
TI  - European network for Health Technology Assessment Joint Action (EUnetHTA JA): a
      process evaluation performed by questionnaires and documentary analysis.
AB  - BACKGROUND: The European network for Health Technology Assessment Joint Action
      (EUnetHTA JA) project's overarching objective was to 'establish an effective and
      sustainable HTA [Health technology assessment] collaboration in Europe that
      brings added value at the regional, national and European level'. Specific
      objectives were to develop a strategy and business model for sustainable European
      collaboration on HTA, develop HTA tools and methods and promote good practice in
      HTA methods and processes. We describe activities performed on behalf of the
      National Institute for Health Research HTA programme; evaluating the project
      processes and developing a data set for a registry of planned clinical studies of
      relevance to public funders. METHODS: Annual self-completion online
      questionnaires were sent to project participants and external stakeholders to
      identify their views about the project processes. Documentary review was
      undertaken at the project end on the final technical reports from the work
      packages to examine whether or not their deliverables had been achieved. The
      project's impact was assessed by whether or not the deliverables were produced,
      the objectives met and additional 'added value' generated. The project's
      effectiveness was evaluated by its processes, communication, administration,
      workings of individual work packages and involvement of external stakeholders. A
      two-stage Delphi exercise was undertaken to identify the data elements that
      should be included in a registry of planned clinical studies of relevance to
      public funders. The data set was validated by an efficacy testing exercise.
      RESULTS AND DISCUSSION: High response rates were achieved for the questionnaires
      sent to project participants and this was attributed to the evidence-based
      strategy implemented. Response rates to questionnaires sent to external
      stakeholders were disappointingly lower. Most of the high-level objectives were
      achieved, although applying the developed tools in practice will be implemented
      in the European network for Health Technology Assessment Joint Action 2 (EUnetHTA
      JA2). Most work packages produced their planned deliverables. Networking emerged
      as one of the main benefits of the project and face-to-face meetings were
      important. However, the overarching objective did not appear to have been met
      because there will be a follow-up EUnetHTA JA2 project (reliant on project
      funding) before the establishment of any permanent network. Twelve organisations
      from three continents participated in the Delphi exercise to develop the data
      set. It was demonstrated that a registry for matching pragmatic clinical studies
      under consideration by funders could be built on a very small data set. This
      would include 10 unique items, of which five are required to describe a study and
      the rest are metadata. In the test sample the data set with an appropriate
      matching rule was able to deliver a sensitivity of between 50% and 100% and a
      specificity of between 43% and 86% for matching different elements. CONCLUSIONS:
      A number of recommendations have been made for the next EUnetHTA JA2 project and
      its evaluation. This included that the evaluation of the EUnetHTA JA2 project
      should extend beyond the end of the project to allow assessment of its impact;
      that the quality, usability and cost-effectiveness of tools in 'real-world HTA
      practice' should be assessed and tangible benefits of international networking
      should be evaluated. It is worth proceeding to develop a database registry aimed
      at identifying trials in development based on the data set developed. FUNDING:
      The study was funded by the National Institute for Health Research Health
      Technology Assessment programme (50%) and the European Union Commission (50%).

PMID- 24913264
TI  - CXCR4/CXCR7 molecular involvement in neuronal and neural progenitor migration:
      focus in CNS repair.
AB  - In the adult brain, neural progenitor cells (NPCs) reside in the subventricular
      zone (SVZ) of the lateral ventricles, the dentate gyrus and the olfactory bulb.
      Following CNS insult, NPCs from the SVZ can migrate along the rostral migratory
      stream (RMS), a migration of NPCs that is directed by proinflammatory cytokines.
      Cells expressing CXCR4 follow a homing signal that ultimately leads to neuronal
      integration and CNS repair, although such molecules can also promote NPC
      quiescence. The ligand, SDF1 alpha (or CXCL12) is one of the chemokines secreted
      at sites of injury that it is known to attract NSC-derived neuroblasts, cells
      that express CXCR4. In function of its concentration, CXCL12 can induce different
      responses, promoting NPC migration at low concentrations while favoring cell
      adhesion via EGF and the alpha 6 integrin at high CXCL12 concentrations. However,
      the preclinical effectiveness of chemokines and their relationship with NPC
      mobilization requires further study, particularly with respect to CNS repair. NPC
      migration may also be affected by the release of cytokines or chemokines induced
      by local inflammation, through autocrine or paracrine mechanisms, as well as
      through erythropoietin (EPO) or nitric oxide (NO) release. CXCL12 activity
      requires G-coupled proteins and the availability of its ligand may be modulated
      by its binding to CXCR7, for which it shows a stronger affinity than for CXCR4.

PMID- 24913265
TI  - Mental health stigma and attitudes to psychiatry among Bangladeshi medical
      students.
AB  - BACKGROUND: The shortage of specialized human resources in mental health in
      Bangladesh requires active recruitment of psychiatric residents. In addition, the
      involvement of positively inclined health personnel, for example, medical
      doctors, emerges as an immediate priority. AIM: To explore stigma among medical
      students toward persons with mental disorders (PMDs) and their attitudes toward
      psychiatry. METHOD: A cross-sectional study was conducted at Faridpur Medical
      College in Bangladesh before (First year) and following psychiatric rotation
      (Fifth year). Students (N = 200) filled anonymous questionnaires measuring stigma
      toward PMDs and attitudes to psychiatry. RESULTS: Upper medical school year (p =
      .028), older age (p = .005), mother's lower academic level (p = .043), upper and
      lower socioeconomic level affiliation (p = .008) and self-consultation for mental
      or neurological complaints (p = .032) were associated with increased stigma
      toward PMDs. More favorable attitudes toward psychiatry were found in upper
      medical school year (p = .073) and were significantly associated with female
      gender (p = .018) and middle socioeconomic level affiliation (p = .013).
      CONCLUSION: The relative improvement in attitudes toward psychiatry in the upper
      medical school year is overshadowed by the increased stigma toward PMDs. Specific
      anti-stigma program in the curriculum and strategies to improve the attitudes are
      required.

PMID- 24913266
TI  - Tiotropium might improve survival in subjects with COPD at high risk of
      mortality.
AB  - BACKGROUND: Inhaled therapies reduce risk of chronic obstructive pulmonary
      disease (COPD) exacerbations, but their effect on mortality is less well
      established. We hypothesized that heterogeneity in baseline mortality risk
      influenced the results of drug trials assessing mortality in COPD. METHODS: The
      5706 patients with COPD from the Understanding Potential Long-term Impacts on
      Function with Tiotropium (UPLIFT(r)) study that had complete clinical information
      for variables associated with mortality (age, forced expiratory volume in 1 s, St
      George's Respiratory Questionnaire, pack-years and body mass index) were
      classified by cluster analysis. Baseline risk of mortality between clusters, and
      impact of tiotropium were evaluated during the 4-yr follow up. RESULTS: Four
      clusters were identified, including low-risk (low mortality rate) patients (n =
      2339; 41%; cluster 2), and high-risk patients (n = 1022; 18%; cluster 3), who had
      a 2.6- and a six-fold increase in all-cause and respiratory mortality compared
      with cluster 2, respectively. Tiotropium reduced exacerbations in all clusters,
      and reduced hospitalizations in high-risk patients (p < 0.05). The beneficial
      effect of tiotropium on all-cause mortality in the overall population (hazard
      ratio, 0.87; 95% confidence interval, 0.75-1.00, p = 0.054) was explained by a
      21% reduction in cluster 3 (p = 0.07), with no effect in other clusters.
      CONCLUSIONS: Large variations in baseline risks of mortality existed among
      patients in the UPLIFT(r) study. Inclusion of numerous low-risk patients may have
      reduced the ability to show beneficial effect on mortality. Future clinical
      trials should consider selective inclusion of high-risk patients.

PMID- 24913267
TI  - Diet composition and feeding ecology of the naked goby Gobiosoma bosc (Gobiidae)
      from four western Atlantic estuaries.
AB  - The feeding ecology of the small-bodied benthic naked goby Gobiosoma bosc, a
      western Atlantic species that occurs in estuaries and other inshore habitats from
      Connecticut to Texas U.S.A., was investigated in a total of four estuaries
      spanning South Carolina, North Carolina, Maryland and New Jersey. Gut content
      analysis of 391 individuals revealed that G. bosc is a benthic microcarnivore
      that feeds primarily on polychaetes, gammarid amphipods and harpacticoid
      copepods. Diet composition varied with body size, tidal creek within an estuary
      and geographic region. Analyses of gut fullness suggest that G. bosc is a daytime
      visual predator and that nest and egg guarding during the reproductive season
      reduce foraging activity in mature males. Additionally, G. bosc infected with
      adult digenean parasites of the gut foraged more intensely than uninfected
      individuals, a relationship that was strongest for reproductively mature males.
      Regionally, significant variation in dietary breadth was documented and may
      reflect a foraging response to a decrease in prey diversity moving from estuaries
      of higher salinity and lower latitude to estuaries of lower salinity and higher
      latitude. These results contribute to an understanding of the life history of G.
      bosc and the role played by this common species in estuarine food webs. 

PMID- 24913270
TI  - The common marmoset as a model for the study of nonalcoholic fatty liver disease
      and nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation
      of metabolic syndrome. The more clinically concerning form of the disease,
      nonalcoholic steatohepatitis (NASH), is characterized by steatosis, lobular
      inflammation, and ballooning degeneration. Here we describe a naturally occurring
      syndrome in the common marmoset that recapitulates the pathologic findings
      associated with NAFLD/NASH in humans. Hepatomegaly determined to result from
      NAFLD was observed in 33 of 183 marmosets. A comprehensive histopathologic
      assessment performed in 31 marmosets demonstrated that NAFLD was characterized by
      variably sized, Oil Red O staining cytoplasmic vacuoles and observed primarily in
      animals with evidence of obesity and insulin resistance. A subset of marmosets
      (16 of 31) also demonstrated evidence of NASH characterized by multifocal
      inflammation combined with ballooning hepatocellular degeneration. Marmosets with
      NASH demonstrated an increase in immunostaining with an antibody targeted against
      the human leukocyte antigens (HLA)-DP, HLA-DQ, and HLA-DR compared with marmosets
      without NASH (38.89 cells/10* field vs 12.05 cells/10* field, P = .05). In
      addition, marmosets with NASH demonstrated increased Ki-67 immunopositive
      cellular proliferation compared with those without (5.95 cells/10* field vs 1.53
      cells/10* field, P = .0002). Finally, animals with NASH demonstrated
      significantly increased mean circulating serum iron levels (160.47 MUg/dl, P =
      .008) and an increase in numbers of Prussian blue-positive Kupffer cells (9.28
      cells/40* field, P = .005) relative to marmosets without NASH (97.75 MUg/dl and
      1.87 cells/40*, respectively). This study further characterizes the
      histopathology of NAFLD/NASH and suggests that the marmoset may be a valuable
      animal model with which to investigate the host and environmental factors
      contributing to the progression of NAFLD/ NASH. 

PMID- 24913269
TI  - Primary intestinal and vertebral chordomas in laboratory zebrafish (Danio rerio).
AB  - Chordomas are uncommon neoplasms arising from notochord remnants, most commonly
      occurring in the axial skeleton. Extraskeletal soft tissue chordomas are rare
      primary tumors, and primary alimentary tract chordomas have not been reported.
      Herein we report 24 cases of spontaneous primary intestinal chordomas in
      zebrafish, as well as 9 spontaneous vertebral chordomas. Both intestinal and
      vertebral tumors showed invasive behavior, although more commonly in the latter.
      In all cases of primary intestinal chordomas, there was no axial or peripheral
      skeletal or other nonvisceral involvement. Although uncommon, intestinal
      chordomas represent a unique background lesion in aged zebrafish. 

PMID- 24913268
TI  - Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti
      protozoan drug emetine.
AB  - Malaria inflicts an enormous burden on global human health. The emergence of
      parasite resistance to front-line drugs has prompted a renewed focus on the
      repositioning of clinically approved drugs as potential anti-malarial therapies.
      Antibiotics that inhibit protein translation are promising candidates for
      repositioning. We have solved the cryo-EM structure of the cytoplasmic ribosome
      from the human malaria parasite, Plasmodium falciparum, in complex with emetine
      at 3.2 A resolution. Emetine is an anti-protozoan drug used in the treatment of
      ameobiasis that also displays potent anti-malarial activity. Emetine interacts
      with the E-site of the ribosomal small subunit and shares a similar binding site
      with the antibiotic pactamycin, thereby delivering its therapeutic effect by
      blocking mRNA/tRNA translocation. As the first cryo-EM structure that visualizes
      an antibiotic bound to any ribosome at atomic resolution, this establishes cryo
      EM as a powerful tool for screening and guiding the design of drugs that target
      parasite translation machinery. 

PMID- 24913271
TI  - The perspectives of patients, family members and healthcare professionals on
      readmissions: preventable or inevitable?
AB  - An understanding of what complex medical patients with chronic conditions, family
      members and healthcare professionals perceive to be the key reasons for the
      readmission is important to preventing their occurrence. In this context, we
      undertook a study to understand the perceptions of patients, family members and
      healthcare professionals regarding the reasons for, and preventability of,
      readmissions. An exploratory case design with semi-structured interviews was
      conducted with 49 participants, including patients, family members, nurses, case
      managers, physicians, discharge planners from a general internal medicine unit at
      a large and academic hospital. Data were analyzed using a directed content
      analysis approach that involved three investigators. Two contrasting themes
      emerged from the analysis of interview data set. The first theme was readmissions
      as preventable occurrences. Our analyses elucidated contributing factors to
      readmissions during the patients' hospital stay and after the patients were
      discharged. The second theme was readmissions as inevitable, occurring due to the
      progression of disease. Our study findings indicate that some readmissions are
      perceived to be inevitable due to the burden of disease while others are
      perceived to be preventable and associated with factors both in hospital and post
      discharge. Continued interprofessional efforts are required to identify patients
      at risk for readmission and to organize and deliver care to improve health
      outcomes after hospitalization.

PMID- 24913272
TI  - Achieving Patient-Centered Care in a Case of a Patient With Advanced Dementia.

PMID- 24913273
TI  - Counteracting the Trajectory of Frailty and Sarcopenia in Older Adults.
AB  - Food preservation technologies and medical advances in the past 50 years have
      contributed to safeguarding the health and prolonging the lives of individuals
      worldwide. However, living longer does not automatically equate with being
      healthy, living independently, making judicious decisions, or setting goals and
      achieving them. Most adults will experience 1 or more health problems with
      lingering consequences. It is the impact of the disease or injury that determines
      overall well-being and quality of life. Frailty, sarcopenia and malnutrition have
      been identified as common geriatric syndromes associated with functional decline,
      disability, hospitalization, institutionalization, and mortality. The evidence
      demonstrates that these geriatric syndromes could be prevented or the course of
      the syndrome altered through prevention strategies. Since these syndromes often
      present concurrently, it is prudent for healthcare professionals to recognize the
      interrelationships and clinical implications of these syndromes to employ tactics
      to promote desirable outcomes.

PMID- 24913274
TI  - Comparing disproportionate exposure to acute and chronic pollution risks: a case
      study in Houston, Texas.
AB  - While environmental justice (EJ) research in the United States has focused
      primarily on the social distribution of chronic pollution risks, previous
      empirical studies have not analyzed disparities in exposure to both chronic (long
      term) and acute (short-term) pollution in the same study area. Our article
      addresses this limitation though a case study that compares social inequities in
      exposure to chronic and acute pollution risks in the Greater Houston Metropolitan
      Statistical Area, Texas. The study integrates estimates of chronic cancer risk
      associated with ambient exposure to hazardous air pollutants from the
      Environmental Protection Agency's National-Scale Air Toxics Assessment (2005),
      hazardous chemical accidents from the National Response Center's Emergency
      Response Notification System (2007-2011), and sociodemographic characteristics
      from the American Community Survey (2007-2011). Statistical analyses are based on
      descriptive comparisons, bivariate correlations, and locally derived spatial
      regression models that account for spatial dependence in the data. Results
      indicate that neighborhoods with a higher percentage of Hispanic residents, lower
      percentage of homeowners, and higher income inequality are facing significantly
      greater exposure to both chronic and acute pollution risks. The non-Hispanic
      black percentage is significantly higher in neighborhoods with greater chronic
      cancer risk, but lower in areas exposed to acute pollution events. Households
      isolated by language--those highly likely to face evacuation problems during an
      actual chemical disaster--tend to reside in areas facing significantly greater
      exposure to high-impact acute events. Our findings emphasize the growing need to
      examine social inequities in exposure to both chronic and acute pollution risks
      in future EJ research and policy.

PMID- 24913276
TI  - Doing health geography with feeling.

PMID- 24913275
TI  - Multiplex congruity: friendship networks and perceived popularity as correlates
      of adolescent alcohol use.
AB  - Adolescents interact with their peers in multiple social settings and form
      various types of peer relationships that affect drinking behavior. Friendship and
      popularity perceptions constitute critical relationships during adolescence.
      These two relations are commonly measured by asking students to name their
      friends, and this network is used to construct drinking exposure and peer status
      variables. This study takes a multiplex network approach by examining the
      congruity between friendships and popularity as correlates of adolescent
      drinking. Using data on friendship and popularity nominations among high school
      adolescents in Los Angeles, California (N = 1707; five schools), we examined the
      associations between an adolescent's drinking and drinking by (a) their friends
      only; (b) multiplexed friendships, friends also perceived as popular; and (c)
      congruent, multiplexed-friends, close friends perceived as popular. Logistic
      regression results indicated that friend-only drinking, but not multiplexed
      friend drinking, was significantly associated with self-drinking (AOR = 3.51, p <
      0.05). However, congruent, multiplexed-friend drinking also was associated with
      self-drinking (AOR = 3.10, p < 0.05). This study provides insight into how
      adolescent health behavior is predicated on the multiplexed nature of peer
      relationships. The results have implications for the design of health promotion
      interventions for adolescent drinking.

PMID- 24913277
TI  - Self-isolated pulmonary vein.

PMID- 24913278
TI  - The generation of definitive endoderm from human embryonic stem cells is
      initially independent from activin A but requires canonical Wnt-signaling.
AB  - The activation of the TGF-beta pathway by activin A directs ES cells into the
      definitive endoderm germ layer. However, there is evidence that activin A/TGF
      beta is not solely responsible for differentiation into definitive endoderm.
      GSK3beta inhibition has recently been shown to generate definitive endoderm-like
      cells from human ES cells via activation of the canonical Wnt-pathway. The
      GSK3beta inhibitor CHIR-99021 has been reported to generate mesoderm from human
      iPS cells. Thus, the specific role of the GSK3beta inhibitor CHIR-99021 was
      analyzed during the differentiation of human ES cells and compared against a
      classic endoderm differentiation protocol. At high concentrations of CHIR-99021,
      the cells were directed towards mesodermal cell fates, while low concentrations
      permitted mesodermal and endodermal differentiation. Finally, the analyses
      revealed that GSK3beta inhibition rapidly directed human ES cells into a
      primitive streak-like cell type independently from the TGF-beta pathway with
      mesoderm and endoderm differentiation potential. Addition of low activin A
      concentrations effectively differentiated these primitive streak-like cells into
      definitive endoderm. Thus, the in vitro differentiation of human ES cells into
      definitive endoderm is initially independent from the activin A/TGF-beta pathway
      but requires high canonical Wnt-signaling activity. 

PMID- 24913279
TI  - The use of adipose stem cells in cranial facial surgery.
AB  - Craniofacial malformations, have devastating psychosocial implications for many
      adults and children and causes huge socioeconomic burden. Currently craniofacial
      defects require soft tissue transfer, bone grafting techniques or difficult
      procedures such as microvascular free flaps. Such tissues are often limited in
      quantity, their harvest causes secondary large donor site defects and they lack
      the capability to fully restore previous form and function. Stem cell technology
      is being utilised for various tissue and organs of the body and consequently
      surgeons are eager to transfer these principles for craniofacial surgery. Adipose
      derived stem cells (ADSCs) are an exciting stem cell source for craniofacial
      surgeons due to their easy and painless isolation, relatively large abundance and
      familiarity with the harvesting procedure. ADSCs also have multiple desirable
      properties including adipogenic, osteogenic and chondrogenic potential,
      enhancement of angiogenesis and immunodulatory function. Due to these
      advantageous characteristics, ASDCs have been explored to repair craniofacial
      bone, soft tissue and cartilage. The desirable characteristics of ADSCs for
      craniofacial surgical applications will be explained. We report the experimental
      and clinical studies that have explored the use of ADSCs for bone, cartilage and
      soft tissue craniofacial defects. We conclude by establishing the key questions
      that are preventing the clinical application of ADSCs for craniofacial surgery. 

PMID- 24913280
TI  - Mll2 controls cardiac lineage differentiation of mouse embryonic stem cells by
      promoting H3K4me3 deposition at cardiac-specific genes.
AB  - Trithorax group (TrxG) proteins play critical roles in transcriptional activation
      by promoting methylation of histone H3 Lysine 4 (H3K4), but the precise functions
      of the individual TrxG members during embryonic differentiation are not fully
      understood. Here we show that Mll2, a TrxG member, is required for proliferation
      but is dispensable for maintaining the pluripotency of mouse embryonic stem cells
      (ESCs). In addition, differentiation of ESCs toward mesodermal and endodermal
      lineages is severely altered and, in particular, the cardiac lineage
      differentiation of ESCs is completely abolished in the absence of Mll2. Moreover,
      the expression of core cardiac transcription factors and the levels of H3K4 tri
      methylation of these cardiac-specific promoters are significantly decreased by
      the loss of Mll2. Taken together, our results reveal a critical role for Mll2 in
      proliferation and cardiac lineage differentiation of mouse ESCs, and provide
      novel molecular insight into the mechanisms of cardiac development and disease. 

PMID- 24913282
TI  - Sonochemically synthesis of arylethynyl linked triarylamines catalyzed by CuI
      nanoparticles: a rapid and green procedure for Sonogashira coupling.
AB  - A simple and green method was performed to the preparation of copper iodide
      nanoparticles by ultrasound approach. Consequently the synthesis of aryl ethynyl
      linked triarylamines was carried out through the Sonogashira coupling between
      iodo-substituted triarylamine and aryl acetylenes in the presence of CuI
      nanoparticles/Pd(PPh3)2Cl2 as an efficient catalytic system and triethylamine as
      the base under ultrasonic irradiation. Good to excellent yields of products and
      short reaction times are some of the important advantages of this solvent free
      protocol which were attained by both nano CuI and ultrasound conditions. 

PMID- 24913281
TI  - Alkaline phosphatase expression/activity and multilineage differentiation
      potential are the differences between fibroblasts and orbital fat-derived stem
      cells--a study in animal serum-free culture conditions.
AB  - Human orbital fat tissues are a potential source to isolate stem cells for the
      development of regenerative medicine therapies. For future safe clinical
      application of these cells, it is critical to establish animal component-free
      culture conditions as well as to clearly define the stem cell population
      characteristics differentiating them from other cell types, such as fibroblasts.
      Therefore, the present study aimed to compare phenotypic and functional
      characteristics of orbital fat-derived stem cells (OFSCs) and fibroblasts
      resident in the eyelid skin in donor-matched samples grown in culture medium
      supplemented with pooled allogeneic human serum (HS) replacing fetal bovine serum
      (FBS). We first investigated the proliferative effects of OFSCs on HS, and then
      we compared the alkaline phosphatase (AP) expression and activity,
      immunophenotypic profile, and in vitro multilineage differentiation potential of
      OFSCs side-by-side with fibroblasts. The results showed that HS enhanced OFSCs
      proliferation without compromising their immunophenotype, AP activity, and
      osteogenic, adipogenic, and chondrogenic differentiation capacities. In contrast
      to OFSCs, the fibroblasts did not exhibit AP expression and activity and did not
      have multilineage differentiation potential. The results enabled us to
      successfully distinguish OFSCs from fibroblasts populations, suggesting that AP
      expression/activity and multilineage differentiation assays can be used reliably
      to discriminate mesenchymal stem cells from fibroblasts. Our findings also
      support the feasibility of pooled allogeneic HS as a safer and more effective
      alternative to FBS for clinical applications. 

PMID- 24913283
TI  - Nationwide incidence of clinically diagnosed central retinal artery occlusion in
      Korea, 2008 to 2011.
AB  - PURPOSE: To define the incidence and demographics of clinically diagnosed central
      retinal artery occlusion (CRAO) in Korea. DESIGN: Nationwide population-based
      retrospective study using data entered into the Korean national health claims
      database from 2007 to 2011. PARTICIPANTS: Data of the entire Korean population (N
      = 47,990,761, based on the 2010 census) were analyzed. METHODS: We used the
      national health claims database to identify patients diagnosed with CRAO.
      Incident cases were those with no claims related to CRAO in 2007 and were
      included once on the earliest claims related to CRAO in the years 2008 to 2011.
      Incident cases had a disease-free period before diagnosis of at least 1 to 4
      years. The average incidence rate of CRAO was estimated according to the entire
      Korean population. MAIN OUTCOME MEASURES: The person-time incidence rates of
      clinically diagnosed CRAO in Korea, including the age- and sex-specific incidence
      rates, were estimated. RESULTS: A total of 3464 CRAO cases (59.1% men) were
      identified. The incidence rate of clinically diagnosed CRAO during the study
      period was 1.80 per 100,000 person-years (95% confidence interval [CI], 1.74
      1.86). The incidence rate among men and women was 2.15 (95% CI, 2.05-2.24) and
      1.47 (95% CI, 1.39-1.54) per 100,000 person-years (male-to-female ratio, 1.47),
      respectively. The age-specific male-to-female ratios were constant between the
      ages of 30 and 89 years (range, 1.51-2.10 years). The highest incidence of 10.08
      (95% CI, 8.80-11.35) per 100,000 person-years was observed in those aged 80 to 84
      years (14.65 [95% CI, 11.90-17.40] and 8.00 [95% CI, 6.63-9.37] per 100,000
      person-years for men and women aged 80-84 years, respectively). The incidence
      rate of CRAO increased exponentially with age until the 9th decade of life.
      CONCLUSIONS: To our knowledge, this is the first nationwide epidemiologic study
      of CRAO in individuals of all ages. The incidence rate of CRAO in Korea increased
      exponentially with increasing age and was highest among those aged 80 to 84
      years. Moreover, the incidence rate in men was 1.47 times higher than that in
      women.

PMID- 24913284
TI  - Outcomes of strabismus surgery with or without trainee participation as surgeon.
AB  - PURPOSE: To compare success rates of strabismus surgery that involves trainees
      versus those performed solely by staff surgeons. DESIGN: Retrospective,
      comparative case series. SUBJECTS: Patients undergoing eye muscle surgery for
      primarily horizontal deviations. METHODS: Retrospective comparative case series
      of 543 patients (921 eyes) undergoing eye muscle surgery, with or without trainee
      participation, for horizontal deviations. MAIN OUTCOME MEASURES: Success in
      surgery defined as residual horizontal deviations of 10 prism diopters or less.
      RESULTS: Trainees were involved in surgeries on 396 patients (672 eyes), whereas
      only staff surgeons operated on 147 patients (249 eyes). After minimum follow-up
      of 8 weeks, there was no overall significant difference between the success rates
      of procedures that involved trainees as surgeons and those that did not (P =
      0.59). CONCLUSIONS: The involvement of trainees as operators in surgeries on
      horizontal eye muscles does not result in a worse outcome than surgeries
      exclusively performed by staff. With a shift toward competency-based education
      and more scrutiny of patient outcomes, these data further support the quality of
      surgical care provided by trainees.

PMID- 24913285
TI  - Confirmatory tests for endotracheal tube insertion depth.

PMID- 24913287
TI  - An alternative technique of the superselective catheterization of the ophthalmic
      artery for intra-arterial chemotherapy of the retinoblastoma: retrograde approach
      through the posterior communicating artery to the ophthalmic artery.
AB  - INTRODUCTION: Superselective intra-arterial chemotherapy (IAC) in retinoblastoma
      has recently become a popular treatment option. In this study, we purposed to
      investigate the effectiveness of the technique of "retrograde approach through
      the posterior communicating artery to the ophthalmic artery (OA)" for IAC.
      METHODS: A total of 12 unilateral retinoblastomas were treated with IAC in 29
      sessions from October 2011 to November 2013. Of the 12 patients, 6 were male and
      6 were female, with ages ranging from 12 to 72 months with a median age of 27.6
      months. Left-to-right ratio for affected eye was 6/6. In the first 4 patients, we
      used the ipsilateral internal carotid artery (ICA) to reach the OA of the
      affected globe (10 sessions). Then, we used the vertebral artery, basilary
      artery, ipsilateral/contralateral P1 segment of the posterior cerebral artery,
      and ipsilateral/contralateral posterior communicating artery, respectively, to
      reach inside the OA at next 15 sessions. RESULTS: At ipsilateral approach,
      fluoroscopy total time ranged from 16 to 34 min (mean 21.5 min), and the angle
      between ophthalmic segment of the ICA and proximal segment of the OA was ranged
      between 34 degrees  and 77 degrees  with an average angle of 53.4 degrees . At
      retrograde approach, fluoroscopy total time ranged from 3 to 12 min (mean 7.5
      min), and the angle between ophthalmic segment of the ICA and proximal segment of
      the OA was ranged between 147 degrees  and 178 degrees  with an average angle of
      148.3 degrees . CONCLUSION: Retrograde approach makes the IAC procedure easier in
      retinoblastoma patients and shortens the fluoroscopy time.

PMID- 24913286
TI  - Distinctive electrophysiological characteristics of right ventricular out-flow
      tract cardiomyocytes.
AB  - Ventricular arrhythmias commonly originate from the right ventricular out-flow
      tract (RVOT). However, the electrophysiological characteristics and Ca(2+)
      homoeostasis of RVOT cardiomyocytes remain unclear. Whole-cell patch clamp and
      indo-1 fluorometric ratio techniques were used to investigate action potentials,
      Ca(2+) homoeostasis and ionic currents in isolated cardiomyocytes from the rabbit
      RVOT and right ventricular apex (RVA). Conventional microelectrodes were used to
      record the electrical activity before and after (KN-93, a Ca(2+) /calmodulin
      dependent kinase II inhibitor, or ranolazine, a late sodium current inhibitor)
      treatment in RVOT and RVA tissue preparations under electrical pacing and ouabain
      (Na(+) /K(+) ATPase inhibitor) administration. In contrast to RVA cardiomyocytes,
      RVOT cardiomyocytes were characterized by longer action potential duration
      measured at 90% and 50% repolarization, larger Ca(2+) transients, higher Ca(2+)
      stores, higher late Na(+) and transient outward K(+) currents, but smaller
      delayed rectifier K(+) , L-type Ca(2+) currents and Na(+) -Ca(2+) exchanger
      currents. RVOT cardiomyocytes showed significantly more pacing-induced delayed
      afterdepolarizations (22% versus 0%, P < 0.05) and ouabain-induced ventricular
      arrhythmias (94% versus 61%, P < 0.05) than RVA cardiomyocytes. Consistently, it
      took longer time (9 +/- 1 versus 4 +/- 1 min., P < 0.05) to eliminate ouabain
      induced ventricular arrhythmias after application of KN-93 (but not ranolazine)
      in the RVOT in comparison with the RVA. These results indicate that RVOT
      cardiomyocytes have distinct electrophysiological characteristics with longer AP
      duration and greater Ca(2+) content, which could contribute to the high RVOT
      arrhythmogenic activity.

PMID- 24913288
TI  - Surface zwitterionization of titanium for a general bio-inert control of plasma
      proteins, blood cells, tissue cells, and bacteria.
AB  - Surface coating of antifouling materials on the substrates offers convenient
      strategies and great opportunities to improve their biocompatibility and
      functions of host substrates for wide biomedical applications. In this work, we
      present a general surface zwitterionization strategy to improve surface
      biocompatibility and antifouling properties of titanium (Ti) by grafting
      zwitterionic poly(sulfobetaine methacrylate) (polySBMA). This method also
      demonstrates its general applicability to graft polySBMA onto Ti surface using
      different anchoring agents of dopamine and silane. The resulting polySBMA grafted
      from dopamine- (pTi-D-pSBMA) and silane-anchored titanium surfaces (pTi-Si-pSBMA)
      surfaces exhibit superlow fouling ability to highly resist the adhesions of
      plasma proteins, platelets, erythrocytes, leukocytes, human fibroblast (HT1080),
      E. coli, and S. epidermidis. The interfacial properties of the surface-modified
      Ti surfaces are analyzed and correlated with their antifouling properties. The
      new method and materials provide a more general, flexible, and robust way to
      produce an excellent nonfouling surface with adjustable interfacial structures of
      grafted polymers, which hopefully can be expanded to wider applications based on
      both the structure and surface superiorities. 

PMID- 24913290
TI  - Telephonic analysis of the snoring sound spectrum.
AB  - OBJECTIVE: Snoring is a sound caused by vibration of collapsed and/or unsteady
      airway walls of the pharynx and soft palate. We compared stored spectra of
      snoring sounds recorded via cell phone (CP) and a microphone placed over the head
      (head phone [HP]). METHODS: Thirty-four snoring patients were included in this
      prospective study. Groups were identified by reference to body mass index (BMI)
      values: group 1, BMI < 25 kg/m2 (n = 8); group 2, BMI 25 to 29 kg/m2 (n = 10);
      and group 3, BMI >= 30 kg/m2 (n = 16). Snoring sounds were recorded using CPs and
      HPs and digitally analyzed. We identified the frequencies with the highest
      snoring powers (F(max) values) and snoring sound intensity levels (SSILs).
      RESULTS: F(max) ranged from 520 to 985 Hz in HP recordings and from 845 to 1645
      Hz in CP recordings. Snoring sound intensity level values increased in proportion
      to BMI and were 6 to 24 dB in HP recordings and 19 to 52 dB in CP recordings.
      Thus, the CP values of F(max) and SSIL were higher than the HP values. In obese
      patients of group 3, almost all F(max) and SSIL values were higher than those of
      groups 1 and 2. In particular, the CP F(max) values were elevated in such
      patients. The advanced technologies used in modern CPs may allow some snoring
      sounds in susceptible individuals to be defined as oronasal. CONCLUSION: Cell
      phone technology allows snoring to be evaluated in patients located in areas
      remote from a hospital. To explore the intensity of snoring and to
      postoperatively monitor the efficacy of surgery used to treat snoring, telephonic
      sound analysis is both new and effective and reduces the need for patient
      attendance at a hospital. Those experiencing severe snoring and/or who are obese
      should be told of what can be done to solve such problems.

PMID- 24913291
TI  - Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.
AB  - OBJECTIVE: This case report is the first documentation of dysphonia and vocal
      fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia
      (HHT). METHODS: Case report of a 40-year-old man with HHT presenting with 2 years
      of worsening hoarseness. RESULTS: Hoarseness corresponded with a period of
      anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold
      telangiectasias, and plica ventricular is suggestive of previous submucosal vocal
      fold hemorrhage and subsequent counterproductive compensation with ventricular
      phonation. CONCLUSION: Hereditary hemorrhagic telangiectasia may present as
      dysphonia with vocal fold telangiectasias and place patients at risk of vocal
      fold hemorrhage.

PMID- 24913289
TI  - Arrhythmic substrate, slowed propagation and increased dispersion in conduction
      direction in the right ventricular outflow tract of murine Scn5a+/- hearts.
AB  - AIM: To test a hypothesis attributing arrhythmia in Brugada Syndrome to right
      ventricular (RV) outflow tract (RVOT) conduction abnormalities arising from Nav
      1.5 insufficiency and fibrotic change. METHODS: Arrhythmic properties of
      Langendorff-perfused Scn5a+/- and wild-type mouse hearts were correlated with
      ventricular effective refractory periods (VERPs), multi-electrode array (MEA)
      measurements of action potential (AP) conduction velocities and dispersions in
      conduction direction (CD), Nav 1.5 expression levels, and fibrotic change, as
      measured at the RVOT and RV. Two-way anova was used to test for both independent
      and interacting effects of anatomical region and genotype on these parameters.
      RESULTS: Scn5a+/- hearts showed greater arrhythmic frequencies during programmed
      electrical stimulation at the RVOT but not the RV. The Scn5a+/- genotype caused
      an independent increase of VERP regardless of whether the recording site was the
      RVOT or RV. Effective AP conduction velocities (CV?s), derived from fitting
      regression planes to arrays of observed local activation times were reduced in
      Scn5a+/- hearts and at the RVOT independently. AP conduction velocity magnitudes
      derived by averaging MEA results from local vector analyses, CV*, were reduced by
      the Scn5a+/- genotype alone. In contrast, dispersions in conduction direction,
      were greater in the RVOT than the RV, when the atrioventricular node was used as
      the pacing site. The observed reductions in Nav 1.5 expression were attributable
      to Scn5a+/-, whereas increased levels of fibrosis were associated with the RVOT.
      CONCLUSIONS: The Scn5a+/- RVOT recapitulates clinical findings of increased
      arrhythmogenicity through reduced CV? reflecting reduced CV* attributable to
      reduced Nav 1.5 expression and increased CD attributable to fibrosis.

PMID- 24913294
TI  - The hippocampal neurovascular niche during normal development and after
      irradiation to the juvenile mouse brain.
AB  - PURPOSE: To investigate the effects of cranial irradiation on the neurovascular
      niche in the young brain. Disruption of this niche has previously been observed
      in the adult rat brain after irradiation. MATERIALS AND METHODS: We subjected
      postnatal day 14 (P14) mice to a single dose of 8 Gy whole brain irradiation and
      measured the distance between microvessels and either neural progenitor cells
      (doublecortin-positive, DCX(+)) or proliferating cells (Ki-67(+)) in the dorsal
      hippocampal subgranular zone (SGZ) 6 hours, 1 week and 7 weeks post-irradiation.
      In addition, pericyte coverage of microvessels in the SGZ was measured. RESULTS:
      DCX(+) and Ki-67(+) cells were located closer to microvessels in the adult brain
      compared to young, still growing brains, constituting new information on normal
      development. We found an increased distance between microvessels and DCX(+) cells
      6 h post-irradiation and between microvessels and Ki-67(+) cells 1 week post
      irradiation. Furthermore, pericyte coverage was transiently decreased by 17% 6 h
      post-irradiation. CONCLUSIONS: The hippocampal neurovascular niche in the young,
      growing brain is transiently disrupted by irradiation. It remains to be
      elucidated what role these transient changes play in the apparently permanent
      ablation of hippocampal neurogenesis previously demonstrated in the same model.

PMID- 24913295
TI  - Anticarcinogenic activity of alpha-difluoromethylornithine, ginseng,
      eleutherococcus, and leuzea on radiation-induced carcinogenesis in female rats.
AB  - PURPOSE: To carry out a comparative study of inhibition of radiation
      carcinogenesis using alpha-difluoromethylornithine (DFMO), tinctures of ginseng,
      eleutherococcus and leuzea in female rats. MATERIALS AND METHODS: Locally bred
      female LIO-strain rats were subjected to a single whole body gamma-irradiation
      dose of 4 Gy at 12 weeks of age. Modifying drugs were given with drinking water
      from the 10th day after irradiation until the end of the experiment (for 16
      months). RESULTS: Irradiated rats developed tumors 70.0-79.6% (malignant tumors:
      43.7-45.0%) with a multiplicity of 1.48-1.75 (malignant: 0.5-0.58), while in
      unirradiated animals the incidence of all/malignant tumors was 21.9%/7.7% with
      multiplicity of 0.22/0.08. In exposed rats tumors most often developed in the
      mammary gland - 57.3%, reproductive and endocrine organs - 27.2%, and other
      localizations - 29.1%. All drugs, except leuzea, significantly reduced incidence
      and multiplicity of tumors, overall or at some localizations in irradiated rats.
      Highest, and practically equal inhibition, was shown by ginseng and DFMO, while
      eleutherococcus was clearly inferior. Ginseng reduced overall tumor incidence and
      multiplicity by 1.5 and 2.4 times, malignant tumor incidence and multiplicity -
      by 2.5 and 2.9 times, respectively. CONCLUSIONS: The ginseng extract is the most
      promising radiation carcinogenesis inhibitor tested.

PMID- 24913296
TI  - Bias in the proportionate mortality ratio analysis of small study populations: a
      case on analyses of radiation and mesothelioma.
AB  - Abstract Purpose: To quantify bias in the proportionate mortality ratio (PMR)
      analysis of small study populations and develop a bias correction methodology.
      MATERIALS AND METHODS: Bias in the PMR analysis of small study populations is
      quantified through algebraic derivation. A simulation procedure is developed to
      evaluate the relationship between bias and study population size. A recently
      published PMR analysis of radiation and mesothelioma among 329 deceased
      registrants in the United States Transuranium and Uranium Registries (USTUR) is
      used as an illustrated example. RESULTS: The proportionate mortality ratios are
      biased and overestimated in small population studies; the smaller the study
      population, the larger the overestimation. As such, the average overestimation of
      PMR for mesothelioma in the analyses of radiation and mesothelioma in USTUR is
      7.2% (95% confidence interval = 5.1%, 9.7%); the PMR overestimation is 22.5% (95%
      confidence interval = 16.8%, 29.1%) when stratified by quartiles of radiation
      doses. CONCLUSIONS: The degree of PMR small sample bias is mainly determined by
      the sample size ratio, which is defined as the ratio of the sample size to the
      number of disease categories in the reference population. Correction for the bias
      is recommended when the sample size ratio is less than 5. The quantification and
      correction algorithm of the PMR small sample bias developed in this research
      supplements the PMR methodology.

PMID- 24913292
TI  - Variable escape from X-chromosome inactivation: identifying factors that tip the
      scales towards expression.
AB  - In humans over 15% of X-linked genes have been shown to 'escape' from X
      chromosome inactivation (XCI): they continue to be expressed to some extent from
      the inactive X chromosome. Mono-allelic expression is anticipated within a cell
      for genes subject to XCI, but random XCI usually results in expression of both
      alleles in a cell population. Using a study of allelic expression from cultured
      lymphoblasts and fibroblasts, many of which showed substantial skewing of XCI, we
      recently reported that the expression of genes lies on a contiunuum between those
      that are subject to inactivation, and those that escape. We now review allelic
      expression studies from mouse, and discuss the variability in escape seen in both
      humans and mice in genic expression levels, between X chromosomes and between
      tissues. We also discuss current knowledge of the heterochromatic features, DNA
      elements and three-dimensional topology of the inactive X that contribute to the
      balance of expression from the otherwise inactive X chromosome. 

PMID- 24913297
TI  - Some properties of the signals involved in unirradiated zebrafish embryos
      rescuing alpha-particle irradiated zebrafish embryos.
AB  - PURPOSE: The in vivo radiation-induced bystander effect (RIBE) and radiation
      induced rescue effect (RIRE) induced between embryos of the zebrafish (Danio
      rerio) by alpha-particle irradiation were studied through the number of apoptotic
      signals revealed at 24 h post fertilization (hpf) through vital dye acridine
      orange staining. MATERIALS AND METHODS: RIBE and RIRE were verified through the
      significant increase and decrease in apoptotic signals in the partnered bystander
      and irradiated embryos, respectively. RESULTS: The medium transfer experiment
      where irradiated zebrafish embryos were rescued through immersion in the medium
      previously conditioned by a larger number of irradiated zebrafish embryos showed
      (a) the involvement of a released stress signal in the induction of RIRE, and (b)
      RIBE and RIRE signals had the same function. With the help of 500 MUM of the
      specific nitric oxide (NO) scavenger cPTIO (2-(4carboxyphenyl)-4,4,5,5
      tetramethyl-imidazoline-1-oxyl-3-oxide), NO was confirmed as an essential
      signaling molecule for inducing both the RIBE and RIRE. On the other hand, the
      treatment with 20 MUM of the carbon monoxide (CO) releasing chemical CORM-3
      (tricarbonylchloro(glycinato)ruthenium (II)) suppressed the manifestations of
      RIBE but did not suppress RIRE. CONCLUSIONS: In conclusion, unirradiated
      zebrafish embryos need NO but not NO-induced damages to rescue alpha-particle
      irradiated zebrafish embryos.

PMID- 24913298
TI  - Response to Editorial Comment to Health-related quality of life after radical
      cystectomy and neobladder reconstruction in women: impact of voiding and
      continence status.

PMID- 24913299
TI  - Angiocentric Glioma: The Infiltrative Glioma with Ependymal Differentiation.
AB  - Angiocentric glioma is an epileptogenic, infiltrative, low grade glial tumor,
      with ependymal and astrocytic differentiation, most commonly seen in young adults
      and the pediatric age group. Herein we report a case of 21-year-old male patient
      who presented with fever and pharmaco-resistant seizures. Computed tomography
      revealed an iso-dense mass lesion in the gyrus rectus of the left frontal lobe.
      On magnetic resonance imaging the mass was hyperintense on both T1- and T2
      weighted images with no contrast enhancement. Histopathological examination
      revealed monomorphous tumor cells diffusely infiltrating the neuropil with
      circumferential, radial, or longitudinal angiocentric alignment and subpial
      aggregation with perpendicular alignment of the cells to the pial surface. Among
      central nervous system tumors with ependymal differentiation, this distinct
      entity is the one with an infiltrating growth pattern. In spite of the
      infiltrating pattern, it does not seem to have a potential for aggressive
      behavior.

PMID- 24913300
TI  - Cutaneous myeloid sarcoma of the penile foreskin.
AB  - Myeloid sarcoma, considered to herald the onset of a blast crisis in the setting
      of chronic myeloproliferative neoplasm/dysplasia, typically presents during the
      course of the disorder. Cutaneous involvement is uncommon and lesions on genital
      skin are seldom seen. We present a case of a well-differentiated myeloid sarcoma
      in the penile foreskin in an apparently healthy 29-year-old male presenting with
      phimosis. The unusual composition of the inflammatory cell infiltrate, and
      characteristic sparing of dermal blood vessels, nerves and smooth muscle fibres
      led to the correct diagnosis. Absence of commonly observed changes in the
      circumcision skin like those of balanitis xerotica was also helpful. Detailed
      hematological work up revealed a previously undiagnosed chronic myeloid leukemia
      in chronic phase. The patient also had simultaneous priapism, another rare
      presentation of chronic myeloid leukemia. One year hence, the patient is in
      hematological remission with no evidence of extramedullary disease. Although
      priapism has been described as a rare presenting symptom in chronic myeloid
      leukemia, the present case is unique as this is the first time a cutaneous
      myeloid sarcoma has been documented in the penile foreskin. 

PMID- 24913301
TI  - A Translocation Renal Cell Carcinoma with Skeletal Muscle Metastasis in a Child.
AB  - Renal cell carcinoma is a tumor that is well known for a high rate of metastasis
      to several locations like the lung, liver and bones. Skeletal muscle is a rare
      location for dissemination of the disease. Herein, we describe a 7-year-old boy
      who presented with flank pain. On physical examination, an abdominal mass located
      on the left kidney as well as a solid palpable lesion on the left upper arm were
      detected. Total nephrectomy with subsequent excision of the arm mass was
      performed. Pathology examination revealed presence of translocation renal cell
      carcinoma. The patient received alpha-interferon followed by multikinase
      inhibitor (Sorafenib) treatment but was lost due to progressive disease. This is
      the first description of a pediatric patient with skeletal muscle metastases of
      translocation renal cell carcinoma in the literature.

PMID- 24913302
TI  - A histopathologic analysis of 50 eyes primarily enucleated for retinoblastoma in
      a tertiary cancer center in Jordan.
AB  - OBJECTIVE: To analyze the histopathologic features of the eyes with intraocular
      retinoblastoma primarily treated by enucleation in a tertiary cancer center in
      Jordan. MATERIAL AND METHOD: A retrospective case series of 50 eyes for 49
      patients who had pathologically confirmed retinoblastoma after enucleation as
      primary therapy. The main outcome measures included demographics, laterality,
      international classification of intraocular retinoblastoma, choroid invasion,
      optic nerve invasion, anterior chamber invasion, and tumor differentiation.
      RESULTS: The median age at enucleation was 30 months. Twenty-seven (55%) patients
      were males, and 19 (39%) patients had bilateral retinoblastoma. High risk
      pathological features were seen as massive choroid invasion in 9 (18%) eyes, post
      laminar optic nerve invasion in 7 (14%) eyes, and anterior chamber, iris or
      ciliary body invasion in 7 (14%) eyes. Thirty-seven (74%) tumors were
      well/moderately differentiated, and 13 (26%) were poorly differentiated. Poorly
      differentiated tumors presented later (median 31 months) than well/ moderately
      differentiated tumors (26 months) and were associated with a higher incidence of
      high-risk pathological features. No single ICRB group C eye had high-risk
      pathological features, while 17% and 4% of group D eyes and 28% and 33% of group
      E eyes had massive choroid invasion and post-laminar optic nerve invasion,
      respectively. Eighteen (36%) patients received adjuvant chemotherapy for high
      risk pathological features, and at median follow up of 40 months, no single case
      had metastasis or was dead. CONCLUSION: Our pathologic findings were similar to
      the developed world. They were supportive of the predictive power of the
      international classification of retinoblastoma staging system for the likelihood
      of high risk pathological features. Poorly differentiated tumors were associated
      with a higher incidence of high risk pathological features than well/moderately
      differentiated tumors.

PMID- 24913303
TI  - TTF-1 may not be a reliable marker for differentiating metastasis from brain
      tumors.
AB  - OBJECTIVE: TTF-1 is widely used as an immunohistochemical marker of lung and
      thyroid tumors. However, TTF-1 expression has been described in tumors from other
      sites. The presence of TTF-1 expression in primary brain tumors is largely
      unclear and has not been clearly specified yet. We characterized expression of
      two TTF-1 clones in primary brain tumors with relevance to tumor types and
      grades. MATERIAL AND METHOD: We studied immunohistochemistry with tissue micro
      array, using both clones (8G7G3/1 and SPT24) in 45 primary brain tumors of
      different types and grades. Our cases consisted of 1 grade I, 7 grade II, 4 grade
      III, 20 grade IV astrocytic tumors; 9 meningiomas, 2 oligodendrogliomas, 1
      schwannoma and 1 medulloblastoma. RESULTS: We have found TTF-1 nuclear staining
      using the SPT24 clone in 4 cases (3 cases were grade IV and 1 was grade III).
      Focal and weak staining was seen in three cases and moderate-strong and diffuse
      staining was seen in one case. All the tumors were negative with clone 8G7G3/1.
      Clone SPT24 was more sensitive but less specific. CONCLUSION: TTF-1 can also be
      expressed in primary brain tumors, particularly grade III to IV tumors. TTF-1
      expression was a rare finding in previous studies, however strong and diffuse
      staining was not observed until today. We think that TTF-1 nuclear expression in
      high-grade astrocytic tumors cannot rule out primaries even when diffuse and
      strong staining. Clinical and pathological parameters should be evaluated
      together.

PMID- 24913305
TI  - Long-term clinical outcomes of selective segmental transforaminal lumbar
      interbody fusion combined with posterior spinal fusion for degenerative lumbar
      scoliosis.
AB  - BACKGROUND: The purpose of the current study was to investigate the long-term
      clinical outcomes of this technique for degenerative scoliosis (DS). METHODS: The
      records of 95 consecutive patients with DS who underwent selective segmental
      transforaminal interbody fusion combined with posterior-instrumented spinal
      fusion in our department from January 1999 to December 2007 were analysed
      retrospectively. Average follow-up was 7.8 years. Recorded clinical outcomes
      included Oswestry Disability Index (ODI), visual analogue scale (VAS) pain scores
      and overall patient satisfaction. Radiographic measurements included coronal Cobb
      angle, apical vertebra translation, Nash-Moe grade, lumbar lordosis (LL) and
      thoracolumbar kyphosis. Comparison of the clinical and radiographic parameters
      before surgery and at final follow-up was studied. Linear correlation analysis
      was applied to analyse the relationship between the clinical and radiological
      results. RESULTS: Average ODI and VAS pain scores were significantly improved at
      final follow-up compared with baseline (P=0.038; P=0.005). Specifically, the
      average ODI score was 32.2+/-8.6 before surgery and 11.1+/-6.8 at final follow
      up; the average VAS score was 8.9+/-2.0 before surgery and 2.0+/-1.2 at final
      follow-up; patient satisfaction was 88.2% (84/95) at final follow-up. In
      addition, Cobb angle, apical vertebra translation and Nash-Moe grade were all
      statistically significantly decreased compared with preoperative values (P=0.019;
      P=0.035; P=0.001). Although LL had significantly increased (P=0.022),
      thoracolumbar kyphosis did not exhibit a significant change (P=0.64). There was
      significant correlation between LL and decreased ODI scores (r=0.62, P=0.01).
      Eleven patients (11.6%) underwent reoperation during the study period.
      CONCLUSION: Selective segmental transforaminal interbody fusion combined with
      posterior-instrumented spinal fusion appears to have reasonable long-term
      clinical and radiographic outcomes for the treatment of DS.

PMID- 24913306
TI  - The surprising Crab pulsar and its nebula: a review.
AB  - The Crab nebula and its pulsar (referred to together as 'the Crab') have
      historically played a central role in astrophysics. True to this legacy, several
      unique discoveries have been made recently. The Crab was found to emit gamma-ray
      pulsations up to energies of 400 GeV, beyond what was previously expected from
      pulsars. Strong gamma-ray flares, of durations of a few days, were discovered
      from within the nebula, while the source was previously expected to be stable in
      flux on these time scales. Here we review these intriguing and suggestive
      developments. In this context we give an overview of the observational properties
      of the Crab and our current understanding of pulsars and their nebulae.

PMID- 24913304
TI  - A cisplatin-resistant head and neck cancer cell line with cytoplasmic p53(mut)
      exhibits ATP-binding cassette transporter upregulation and high glutathione
      levels.
AB  - PURPOSE: Head and neck squamous cell carcinoma (HNSCC) cell lines with
      cytoplasmically sequestered mutant p53 (p53(mut_c)) are frequently more resistant
      to cisplatin (CDDP) than cells with mutant but nuclear p53 (p53(mut_n)). The aim
      of the study was to identify underlying mechanisms implicated in CDDP resistance
      of HNSCC cells carrying cytoplasmic p53(mut). METHODS: Microarray analysis,
      quantitative reverse transcription polymerase chain reaction, Western blot
      analysis and immunocytochemistry were used to identify and evaluate candidate
      genes involved in CDDP resistance of p53(mut_c) cells. RNAi knockdown or
      treatment with inhibitors together with flow cytometry-based methods was used for
      functional assessment of the identified candidate genes. Cellular metabolic
      activity was assessed with the XTT assay, and the redox capacity of cells was
      evaluated by measuring cellular glutathione (GSH) levels. RESULTS: Upregulation
      of ABCC2 and ABCG2 transporters was observed in CDDP-resistant p53(mut_c) HNSCC
      cells. Furthermore, p53(mut_c) cells exhibited a pronounced side population that
      could be suppressed by RNAi knockdown of ABCG2 as well as treatment with the ATP
      binding-cassette transporter inhibitors imatinib, MK571 and tariquidar. Metabolic
      activity and cellular GSH levels were higher in CDDP-resistant p53(mut_c) cells,
      consistent with a higher capacity to fend off cytotoxic oxidative effects such as
      those caused by CDDP treatment. Finally, ABCC2/G2 inhibition of HNSCC cells with
      MK571 markedly enhanced CDDP sensitivity of HNSCC cells. CONCLUSIONS: The
      observations in this study point to a major role of p53(mut_c) in conferring a
      stem cell like phenotype to HNSCC cells that is associated with ABCC2/G2
      overexpression, high GSH and metabolic activity levels as well as CDDP
      resistance.

PMID- 24913307
TI  - Spinal 5-HT3 receptors mediate descending facilitation and contribute to
      behavioral hypersensitivity via a reciprocal neuron-glial signaling cascade.
AB  - BACKGROUND: It has been recently recognized that the descending serotonin (5-HT)
      system from the rostral ventromedial medulla (RVM) in the brainstem and the 5-HT3
      receptor subtype in the spinal dorsal horn are involved in enhanced descending
      pain facilitation after tissue and nerve injury. However, the mechanisms
      underlying the activation of the 5-HT3 receptor and its contribution to
      facilitation of pain remain unclear. RESULTS: In the present study, activation of
      spinal 5-HT3 receptors by intrathecal injection of a selective 5-HT3 receptor
      agonist SR 57227 induced spinal glial hyperactivity, neuronal hyperexcitability
      and pain hypersensitivity in rats. We found that there was neuron-to-microglia
      signaling via the chemokine fractalkine, microglia to astrocyte signaling via
      cytokine IL-18, astrocyte to neuronal signaling by IL-1beta, and enhanced
      activation of NMDA receptors in the spinal dorsal horn. Glial hyperactivation in
      spinal dorsal horn after hindpaw inflammation was also attenuated by molecular
      depletion of the descending 5-HT system by intra-RVM Tph-2 shRNA interference.
      CONCLUSIONS: These findings offer new insights into the cellular and molecular
      mechanisms at the spinal level responsible for descending 5-HT-mediated pain
      facilitation during the development of persistent pain after tissue and nerve
      injury. New pain therapies should focus on prime targets of descending
      facilitation-induced glial involvement, and in particular the blocking of
      intercellular signaling transduction between neurons and glia.

PMID- 24913309
TI  - Bartter-like syndrome in patients with molecular defects of the insulin receptor
      gene.

PMID- 24913308
TI  - Specific regions display altered grey matter volume in MU-opioid receptor
      knockout mice: MRI voxel-based morphometry.
AB  - BACKGROUND AND PURPOSE: MU Opioid receptor knockout (MOP-KO) mice display several
      behavioural differences from wild-type (WT) littermates including differential
      responses to nociceptive stimuli. Brain structural changes have been tied to
      behavioural alterations noted in transgenic mice with targeting of different
      genes. Hence, we assess the brain structure of MOP-KO mice. EXPERIMENTAL
      APPROACH: Magnetic resonance imaging (MRI) voxel-based morphometry (VBM) and
      histological methods were used to identify structural differences between
      extensively backcrossed MOP-KO mice and WT mice. KEY RESULTS: MOP-KO mice
      displayed robust increases in regional grey matter volume in olfactory bulb,
      several hypothalamic nuclei, periaqueductal grey (PAG) and several cerebellar
      areas, most confirmed by VBM analysis. The largest increases in grey matter
      volume were detected in the glomerular layer of the olfactory bulb, arcuate
      nucleus of hypothalamus, ventrolateral PAG (VLPAG) and cerebellar regions
      including paramedian and cerebellar lobules. Histological analyses confirm
      several of these results, with increased VLPAG cell numbers and increased
      thickness of the olfactory bulb granule cell layer and cerebellar molecular and
      granular cell layers. CONCLUSIONS AND IMPLICATIONS: MOP deletion causes
      previously undescribed structural changes in specific brain regions, but not in
      all regions with high MOP receptor densities (e.g. thalamus, nucleus accumbens)
      or that exhibit adult neurogenesis (e.g. hippocampus). Volume differences in
      hypothalamus and PAG may reflect behavioural changes including hyperalgesia.
      Although the precise relationship between volume change and MOP receptor deletion
      was not determined from this study alone, these findings suggest that levels of
      MOP receptor expression may influence a broader range of neural structure and
      function in humans than previously supposed. LINKED ARTICLES: This article is
      part of a themed section on Opioids: New Pathways to Functional Selectivity. To
      view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24913310
TI  - The first sphingosine 1-phosphate lyase inhibitors against multiple sclerosis: a
      successful drug discovery tale.
AB  - Modulation of sphingosine 1-phosphate (S1P) signaling represents a solid
      opportunity for multiple sclerosis (MS) treatment. In this issue, a team at
      Novartis reports on the identification of the first direct S1P lyase (S1PL)
      inhibitors as new MS agents. One of the most potent inhibitors reported in their
      work was demonstrated to be orally bioavailable and fully protective in a MS
      disease animal model. This work represents an outstanding example of a drug
      discovery campaign that started with the target identification and validation and
      culminated with the preclinical tests on animal disease models. 

PMID- 24913311
TI  - A multicenter clinical evaluation of Mycobacterium tuberculosis IgG/IgM antibody
      detection using the colloidal gold method.
AB  - A specific immunoassay method with the colloidal gold labeling technique has been
      developed more and more for tuberculosis (TB) diagnosis. The aim of this
      multicenter clinical evaluation was to evaluate the performance of a new
      serological diagnostic kit (the Trustline TB IgG/IgM Rapid Test kit) for the
      detection of Mycobacterium tuberculosis infection in China, with the Aupu TB Ab
      (IgG) Colloidal Gold Test kit being used as a control. A total of 1,009 specimens
      were collected from three TB hospitals, including 628 patients with TB, and 219
      non-TB and 162 healthy patients as negative controls. According to the clinical
      diagnostic results, the sensitivities of the Trustline kit and the Aupu kit were
      61.3 % and 53.7 %, respectively. Using the bacteriological test results as the
      "gold standard" to compare the results of the two kits, the sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      and Youden index (YI) were 77.60 %, 79.8 %, 73.31 %, 81.50 %, and 0.574 by the
      Trustline kit, and 67.86 %, 88.9 %, 83.27 %, 77.40 %, and 0.568 by the Aupu kit,
      respectively. Further, the sensitivity of the Trustline kit and the Aupu kit for
      the smear staining and the bacterial culture being positive was 75.6 %, 76.6 %
      and 65.6 %, 66.5 %, and for the negative result, it was 53.8 %, 50.9 % and 47.5
      %, 45.0 %, respectively. Additionally, 35 specimens were IgM-positive by the
      Trustline kit; of these, 30 (4.8 %) were from patients with TB and 5 (1.3 %) were
      from individuals without TB. The results showed that the experimental test had a
      much higher sensitivity than the other commercial test and exhibited a good
      detection rate for M. tuberculosis infection. Therefore, this kit can be used in
      the supplementary diagnosis and screening of TB.

PMID- 24913312
TI  - Timeframe for return to driving for patients with minimally invasive knee
      arthroplasty is associated with knee performance on functional tests.
AB  - BACKGROUND: This study hopes to establish the timeframe for a safe return to
      driving under different speed conditions for patients after minimally invasive
      total knee arthroplasty and further explores how well various kinds of functional
      tests on knee performance can predict the patients' braking ability. METHODS: 14
      patients with right knee osteoarthritis were included in the present study and
      instructed to perform three simulated driving tasks at preoperative, 2 weeks
      postoperative and 4 weeks postoperative. RESULTS: The results showed that the
      total braking time at 4 week postoperative has attained the preoperative level at
      the driving speed 50 and 70 km/hr but not at the driving speed 90 km/hr. It had
      significantly improving in knee reaction time and maximum isometric force at 4
      weeks postoperative. Besides, there was a moderate to high correlation between
      the scores of the step counts and the total braking time. CONCLUSIONS: Summary,
      it is recommended that driving may be resumed 4 weeks after a right knee
      replacement but had to drive at low or moderate speed and the best predictor of
      safety driving is step counts.

PMID- 24913313
TI  - Microbiota: host interactions in mucosal homeostasis and systemic autoimmunity.
AB  - The vertebrate intestinal tract is colonized by hundreds of species of bacteria
      that must be compartmentalized and tolerated to prevent invasive growth and
      harmful inflammatory responses. Signaling initiated by commensal bacteria shapes
      antigen-specific mucosal and systemic adaptive immunity. A distinct type of
      effector CD4(+) T cells, Th17 cells, have a key role in coordinating the
      inflammatory immune responses that afford protection to pathogens at the mucosal
      interface. Balancing this powerful inflammatory response, regulatory T cells
      limit collateral damage and provide antigen-specific tolerance to both food and
      microbial antigens. Here, we discuss the implications for how the microbiota as a
      whole contributes to compartmentalization from the host and how individual
      constituents of the microbiota influence the functions and repertoire of effector
      T cells and organ-specific autoimmune disease. 

PMID- 24913314
TI  - Truth or consequences in the diagnosis of substance use disorders.
AB  - AIMS: This commentary critically evaluates the use of substance-related negative
      psychosocial and health consequences to define and diagnose alcohol and other
      substance use disorders. METHODS: Narrative review. RESULTS: The consequences of
      substance use cause much suffering and are major public health and economic
      problems. However, there are a number of conceptual and measurement problems with
      using consequences as diagnostic criteria for substance disorders. Data indicate
      that substance-related consequences introduce systematic bias and degrade the
      validity of diagnostic systems. CONCLUSIONS: Negative psychosocial and health
      consequences of substance use should play a fundamentally reduced role in modern
      diagnostic systems for, and definitions of, addictive disorders.

PMID- 24913315
TI  - Optical excitation and external photoluminescence quantum efficiency of Eu3+ in
      GaN.
AB  - We investigate photoluminescence of Eu-related emission in a GaN host consisting
      of thin layers grown by organometallic vapor-phase epitaxy. By comparing it with
      a reference sample of Eu-doped Y2O3, we find that the fraction of Eu(3+) ions
      that can emit light upon optical excitation is of the order of 1%. We also
      measure the quantum yield of the Eu-related photoluminescence and find this to
      reach (~10%) and (~3%) under continuous wave and pulsed excitation, respectively.

PMID- 24913316
TI  - The alcohol industry, charities and policy influence in the UK.
AB  - BACKGROUND: Charities exist to pursue a public benefit, whereas corporations
      serve the interests of their shareholders. The alcohol industry uses corporate
      social responsibility activities to further its interests in influencing alcohol
      policy. Many charities also seek to influence alcohol and other policy. The aim
      of this study was to explore relationships between the alcohol industry and
      charities in the UK and whether these relationships may be used as a method of
      influencing alcohol policy. METHODS: The charity regulator websites for England
      and Wales and for Scotland were the main data sources used to identify charities
      involved in UK alcohol policy making processes and/or funded by the alcohol
      industry. RESULTS: Five charities were identified that both receive alcohol
      industry funding and are active in UK alcohol policy processes: Drinkaware; the
      Robertson Trust; British Institute of Innkeeping; Mentor UK and Addaction. The
      latter two are the sole remaining non-industry non-governmental members of the
      controversial responsibility deal alcohol network, from which all other public
      health interests have resigned. CONCLUSION: This study raises questions about the
      extent to which the alcohol industry is using UK charities as vehicles to further
      their own interests in UK alcohol policy. Mechanisms of industry influence in
      alcohol policy making globally is an important target for further investigations
      designed to assist the implementation of evidenced-based policies.

PMID- 24913318
TI  - The big five personality factors as predictors of driving status in older adults.
AB  - OBJECTIVE: Although factors including cognitive and health status have been
      associated with driving cessation in older adults, the role of psychosocial
      variables is not well studied. Previous research on young adult drivers has
      suggested that personality may be related to driving behavior, but this study is
      among the first to explore the relationship between driving status and the Big
      Five Model of personality for older adults. METHOD: Data are from the Health and
      Retirement Study (2008 wave, n = 4,028). Descriptive, bivariate, and multiple
      logistic regression analyses were conducted. RESULTS: Neuroticism (beta = 
      0.4511, p < .001) and agreeableness (beta = -0.5058, p < .001) were associated
      with decreased likelihood of driving; extraversion (beta = 0.4588, p < .001),
      openness (beta = 0.5903, p < .001), and conscientiousness (beta = 0.4077, p <
      .001) were associated with increased likelihood of driving, although results were
      partially mediated by including known risk factors. People who limited their
      driving to nearby locations were the most different from those who no longer
      drove. DISCUSSION: Personality adds a unique contribution to the prediction of
      late-life driving status.

PMID- 24913317
TI  - Impact of obesity and physical activity on functional outcomes in the elderly:
      data from NHANES 2005-2010.
AB  - OBJECTIVE: The objective of this study was to (a) to examine whether the
      association between obesity and physical functioning among older adults is
      moderated by physical activity (PA) and (b) to test whether this moderating
      effect varies by gender. METHOD: Data from adults (aged >60 years) who
      participated in the National Health and Nutrition Examination Surveys (2005-2010)
      were analyzed. Using multivariate logistic regression, we estimated the
      prevalence ratio (PR) of functional limitations and impairment in activities of
      daily living and instrumental activities of daily living, by body mass index and
      PA, while adjusting for age, educational level, and a comorbidity index. RESULTS:
      The sample included 5,304 subjects (mean age = 70.4 years), and 50.5% were
      female. Overweight and obesity were associated with higher levels of functional
      limitations when compared with normal weight individuals regardless of the PA
      status (PR = 1.47, 95% confidence interval [CI] [1.17, 1.85], and PR = 2.71, 95%
      CI [2.00, 3.67], respectively) even after adjustment for confounders. DISCUSSION:
      Overweight and obesity are associated with impairment in functional outcomes
      irrespective of PA.

PMID- 24913319
TI  - A glimpse into the process of gaining permission for the educational dissection
      of human cadavers in the Ottoman Empire.
AB  - Dissection of the human body for educational purposes became officially permitted
      in the Ottoman Empire only after a long, difficult process. In the West, studies
      based on the findings of Galen had been taboo during a long period in which
      dissection of human bodies had been prohibited. Although the first dissection
      studies since ancient times began to appear in the Western literature in the late
      13th and early 14th centuries, the post-Galen taboo against dissection was broken
      only in the 16th century by the studies of Vesalius. However, in the Eastern
      World, it was only fairly recently that the idea of the "sanctity of the human
      body" could be challenged. In the medieval Islamic world, as during the Middle
      Ages in the West, prohibitions against the dissection of human cadavers continued
      for social and religious reasons, although the Koran does not specifically ban
      such dissection. This prohibition also continued through the Ottoman era, which
      began in the 14th century. The first efforts to end the prohibition on dissection
      in the Ottoman Empire were made at the beginning of the 19th century during the
      reign of Sultan Selim III but official permission for dissection was given only
      in 1841 during the reign of Sultan Abdulmecid. Educational dissections in the
      Ottoman Empire officially began at the Istanbul Medical School following the
      granting of this permission. This article will discuss the attempts to end the
      prohibition of dissection in Ottomans within the scope of the history of
      anatomical study in Turkey.

PMID- 24913320
TI  - Flotillin-1 expression in human clear-cell renal cell carcinoma is associated
      with cancer progression and poor patient survival.
AB  - The present study was designed to elucidate the expression levels and the
      proliferative effect of flotillin-1, an integral membrane protein encoded by the
      FLOT1 gene, in human clear-cell renal cell carcinoma (RCC). Flotillin has been
      implicated in other types of cancer, but the role of flotillin in RCC has not
      been established. Immunohistochemistry and western blotting were used to
      determine FLOT1 protein expression levels in RCC samples from 182 patients who
      underwent nephrectomy. FLOT1 mRNA expression levels were analyzed using reverse
      transcription (RT) and RT-quantitative polymerase chain reaction (PCR). The
      association between FLOT1 expression levels in the tumor samples and patient
      survival time was examined using Kaplan-Meier analysis. To demonstrate the
      proliferative effect of FLOT1 on RCC cells, a FLOT1 vector was transfected into
      four RCC cell lines and FLOT1 expression was inhibited using small interfering
      RNA. The proliferative ability of the RCC cells was investigated using a WST-1
      assay and xenograft experiments with BALB/C nude mice. The results demonstrated
      that FLOT1 expression levels were significantly higher in RCC cell samples from
      patients than in healthy renal tissue, and the expression levels were associated
      with tumor stage, size and histological grade. In addition, FLOT1 significantly
      enhanced the proliferation of RCC cell lines in vitro and in vivo. These findings
      suggest that FLOT1, which is upregulated in RCC, is involved in RCC cell
      proliferation, tumorigenesis and progression. Therefore, FLOT1 is an independent
      prognostic marker and therapeutic target for patients with clear-cell RCC. 

PMID- 24913321
TI  - Outdoor pedestrian fall-related injuries among Swedish senior citizens--injuries
      and preventive strategies.
AB  - Senior citizens get around, to a large extent, as pedestrians, and safe walking
      is desirable for senior citizens allowing them to stay mobile, independent and
      healthy in old age. Senior citizens are over-represented in injury statistics,
      and fall-related injuries are common. The aim of this study was to investigate
      fall-related injuries including healthcare costs among senior citizen pedestrians
      injured when walking in public outdoor environments and to describe their self
      reported causes and suggested preventive strategies. The data were based on a
      combination of information from injury data and a questionnaire. Three hundred
      senior citizens attended one emergency department after sustaining injuries from
      pedestrian falls; 60% suffered nonminor injuries, mostly fractures. One-fifth of
      the pedestrians were hospitalised for an average of 8 days with an indirect
      hospital cost of 6.2 million EUR (55 million SEK). Environmental factors such as
      ice were the most commonly described cause of the injury incident. Forty per cent
      of the respondents indicated that the municipality was responsible for the cause
      of the injury incident. Fewer respondents mentioned their own responsibility as a
      preventive strategy. Thirty per cent described a combination of improvements such
      as better road maintenance, changes in human behaviour and use of safety products
      as preventive strategies. It is of great importance to highlight general safety,
      products and preventive strategies to minimise injury risks, so that pedestrians
      can safely realise the known health benefits of walking and thereby limit
      healthcare costs.

PMID- 24913322
TI  - Human renal fibroblasts generate dendritic cells with a unique regulatory
      profile.
AB  - Fibroblasts reside within the renal interstitium in close proximity to
      neighbouring dendritic cells (DCs). It is likely that these cells have a central
      role in the maintenance and function of resident and infiltrating renal DCs,
      though studies to confirm this have been lacking. We investigated whether renal
      fibroblasts influence human DC generation and function. We found that co-culture
      with renal fibroblasts led to the generation of monocyte-derived dendritic cells
      (Fibro-DCs), with significantly reduced CD80, CD83 and CD86 but elevated B7H1 and
      B7DC expression. In addition, these Fibro-DCs displayed a reduced capacity to
      produce interleukin (IL)-12p40 and IL-12p70 but maintained normal levels of IL-23
      and IL-27. Furthermore, IL-10 production was elevated, which together resulted in
      a regulatory DC population with a reduced capacity to stimulate allogenic T-cell
      proliferation and interferon gamma production, while preserving IL-17A.
      Supernatant transfer experiments suggested that a soluble mediator from the
      fibroblasts was sufficient to inhibit the immunogenic capability of DCs. Further
      experiments demonstrated that IL-6 was at least partially responsible for the
      modulating effect of renal fibroblasts on DC generation and subsequent function.
      In summary, renal fibroblasts may have a crucial decisive role in regulating
      local DC immune responses in vivo. Better understanding of this cell population
      and their mechanisms of action may have therapeutic relevance in many immune
      driven renal diseases. 

PMID- 24913323
TI  - HIV-specific antibody-dependent phagocytosis matures during HIV infection.
AB  - Antibody-dependent phagocytosis (ADP) is a potentially important immune mechanism
      to clear HIV. How HIV-specific ADP responses mature during HIV infection or in
      response to vaccinations administered, including the partially successful RV144
      HIV vaccine, is not known. We established a modified ADP assay to measure
      internalisation of HIV antibody (Ab)-opsonised targets using a specific
      hybridisation internalisation probe. Labelled beads were coated with both
      biotinylated HIV gp140 envelope protein and a fluorescent internalisation probe,
      opsonised with Abs and incubated with a monocytic cell line. The fluorescence
      derived from the fluorescent internalisation probe on surface-bound beads, but
      not from internalised beads, was quenched by the addition of a complementary
      quencher probe. HIV Env-specific ADP was measured in 31 subjects during primary
      infection and early chronic HIV infection. Although ADP responses were present
      early during HIV infection, a significant increase in ADP responses in all 31
      subjects studied was detected (P<0.001). However, when we tested 30 HIV-negative
      human subjects immunised with the Canarypox/gp120 vaccine regimen (subjects from
      the RV144 trial) we did not detect HIV-specific ADP activity. In conclusion, a
      modified assay was developed to measure HIV-specific ADP. Enhanced ADP responses
      early in the course of HIV infection were observed but no ADP activity was
      detected following the vaccinations administered in the RV144 trial. Improved
      vaccine regimens may be needed to capitalise on ADP-mediated immunity against
      HIV. 

PMID- 24913324
TI  - Human immunoglobulin classes and subclasses show variability in VDJ gene mutation
      levels.
AB  - Somatic point mutations provide glimpses into B-cell histories, and mutation
      numbers generally correlate with antibody affinity. We recently proposed a model
      of human isotype function, based in part on mutation analysis, in which the
      dominant pathway of isotype switching involves B cells moving sequentially
      through the four immunoglobulin (Ig) G subclasses. This should result in
      predictable differences in affinity between isotypes, and this helps explain how
      different isotypes work together. The model built on analysis of rearranged
      immunoglobulin heavy chain sequences amplified from Papua New Guinean villagers,
      which showed highly significant differences in the mean number of V-REGION
      mutations in sequences, associated with the different IgG subclasses. To
      determine whether this relationship between mutation levels and isotypes is a
      more general phenomenon, the present study was conducted in healthy, urban
      residents of Sydney, Australia. VDJ sequences were generated from eight
      individuals, using 454 pyrosequencing, from cells expressing all isotypes except
      IgD and IgE. This resulted in 35 118 unique, productive VDJ sequences for the
      study. The data confirm that VDJ genes associated with progressively more 3' Ig
      heavy chain gamma (IGHG) constant region genes show increasing levels of point
      mutation. Mean V-REGION mutations in IgA1 and IgA2 sequences were similar.
      Patterns of mutations also differed between isotypes. Despite their association
      with T-independent responses, IgG2 sequences showed significantly more mutational
      evidence of antigen selection than other IgG isotypes. Antigen selection was also
      significantly higher in IgA2 than in IgA1 sequences, raising the possibility of a
      preferential switch pathway from IGHG2 to IGHA2. 

PMID- 24913325
TI  - Keeping peace with the microbiome: acetate dampens inflammatory cytokine
      production in intestinal epithelial cells.

PMID- 24913326
TI  - Association of birth of girls with postnatal depression and exclusive
      breastfeeding: an observational study.
AB  - OBJECTIVES AND HYPOTHESIS: To examine the influence of gender of the baby on
      exclusive breastfeeding and incidence of postnatal depression (PND). We
      hypothesise that in a society with a male gender bias there may be more PND and
      less exclusive breastfeeding of the girl child. DESIGN: Prospective study.
      SETTING: The study was conducted in an urban, tertiary hospital in Delhi.
      PARTICIPANTS: Mothers delivering normally with their babies roomed-in.1537
      eligible women participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Exclusive breastfeeding within the first 48 h of life and score on the Edinburgh
      Postnatal Depression Scale (EPDS) were recorded. RESULTS: 3466 babies were born
      in the hospital. There were 792 girls for every 1000 boys. Among primiparous
      women, the sex ratio was 901 girls per 1000 boys. For second babies, the sex
      ratio was 737:1000. If the first child was a girl the birth ratio fell to 632.
      1026 mothers were exclusively breastfeeding. Exclusive breastfeeding of boys was
      significantly higher (70.8% vs 61.5%, p<0.001). The EPDS score was significantly
      higher with the birth of girls (EPDS 6.0+/-3.39 vs 5.4+/-2.87, p<0.01). Women
      with an EPDS score >11 were less likely to exclusively breastfeed (p<0.01).
      CONCLUSIONS: The results point to a pro-male gender bias evidenced by a low sex
      ratio at birth, higher EPDS score in mothers of girls and less breastfeeding of
      female children.

PMID- 24913327
TI  - Prevalence of prediabetes in England from 2003 to 2011: population-based, cross
      sectional study.
AB  - OBJECTIVE: Prediabetes is a high-risk state for developing diabetes and
      associated complications. The purpose of this paper was to report trends in
      prevalence of prediabetes for individuals aged 16 and older in England without
      previously diagnosed diabetes. SETTING: Data collected by the Health Survey for
      England (HSE) in England in the years 2003, 2006, 2009 and 2011. PARTICIPANTS:
      Individuals aged 16 and older who participated in the HSE and provided a blood
      sample. PRIMARY OUTCOME VARIABLE: Individuals were classified as having
      prediabetes if glycated haemoglobin was between 5.7% and 6.4% and were not
      previously diagnosed with diabetes. RESULTS: The prevalence rate of prediabetes
      increased from 11.6% to 35.3% from 2003 to 2011. By 2011, 50.6% of the population
      who were overweight (body mass index (BMI)>25) and >=40 years of age had
      prediabetes. In bivariate relationships, individuals with greater socioeconomic
      deprivation were more likely to have prediabetes in 2003 (p=0.0008) and 2006
      (p=0.0246), but the relationship was not significant in 2009 (p=0.213) and 2011
      (p=0.3153). In logistic regressions controlling for age, sex, race/ethnicity, BMI
      and high blood pressure, the second most socioeconomically deprived had a
      significantly elevated risk of having prediabetes (2011, OR=1.45; 95% CI 1.26 to
      1.88). CONCLUSIONS: There has been a marked increase in the proportion of adults
      in England with prediabetes. The socioeconomically deprived are at substantial
      risk. In the absence of concerted and effective efforts to reduce risk, the
      number of people with diabetes is likely to increase steeply in coming years.

PMID- 24913328
TI  - Diet pills and the cataract outbreak of 1935: reflections on the evolution of
      consumer protection legislation.
AB  - An outbreak of cataracts in 1935 caused by dinitrophenol (DNP), the active
      ingredient of popular diet pills, highlighted the inability of the U.S. Food and
      Drug Administration (FDA) to prevent harmful drugs from entering the marketplace.
      Just two years earlier, the FDA used horrific images of ocular surface injury
      caused by cosmetics at the World's Fair in Chicago to garner public support for
      legislative reform. The FDA had to walk a fine line between a public awareness
      campaign and lobbying Congress while lawmakers debated the need for consumer
      protection. The cataract outbreak of 1935 was conspicuous in the medical
      literature during the height of New Deal legislation, but questions persist as to
      how much it affected passage of the proposed Food, Drug, and Cosmetic Act (of
      1938). The legislation languished in committee for years. The cataract outbreak
      probably had little impact on the eventual outcome, but medical opinion
      concerning the safety of DNP may have contributed to the voluntary withdrawal of
      the diet drug from the market. We review the DNP cataract outbreak and examine it
      in context of the challenges facing regulatory reform at that time. 

PMID- 24913329
TI  - Uses of the word "macula" in written English, 1400-present.
AB  - We compiled uses of the word "macula" in written English by searching multiple
      databases, including the Early English Books Online Text Creation Partnership,
      America's Historical Newspapers, the Gale Cengage Collections, and others.
      "Macula" has been used: as a non-medical "spot" or "stain", literal or
      figurative, including in astronomy and in Shakespeare; as a medical skin lesion,
      occasionally with a following descriptive adjective, such as a color (macula
      alba); as a corneal lesion, including the earliest identified use in English,
      circa 1400; and to describe the center of the retina. Francesco Buzzi described a
      yellow color in the posterior pole ("retina tinta di un color giallo") in 1782,
      but did not use the word "macula". "Macula lutea" was published by Samuel Thomas
      von Sommering by 1799, and subsequently used in 1818 by James Wardrop, which
      appears to be the first known use in English. The Google n-gram database shows a
      marked increase in the frequencies of both "macula" and "macula lutea" following
      the introduction of the ophthalmoscope in 1850. "Macula" has been used in
      multiple contexts in written English. Modern databases provide powerful tools to
      explore historical uses of this word, which may be underappreciated by
      contemporary ophthalmologists.

PMID- 24913330
TI  - Acute visual loss: just the beginning?
AB  - A 47-year-old man presented with sudden visual loss, optic disk edema, retinal
      ischemia, and limited upgaze in the left eye. Initial MRI revealed thickened,
      enhancing left optic nerve. Extensive work-up for an inflammatory and
      infiltrative etiology was positive only for Borrelia burgdorferi IgM by Western
      blot. Six weeks later the patient had numbness and weakness on his left side. MRI
      showed enhancing lesions extending from the left optic nerve to the optic chiasm,
      along the visual pathways bilaterally, mainly on the right side from optic tract
      to lateral geniculate body and pulvinar. Stereotactic biopsy of the right
      pulvinar lesion revealed glioblastoma. The tumor progressed rapidly, and the
      patient died 11 weeks after the onset of first symptoms. 

PMID- 24913331
TI  - A school of red herring.
AB  - A 66-year-old man with chronic kidney disease presented with painless unilateral
      vision loss and bilateral optic disk swelling. Vision loss progressed in the
      affected eye and developed in the fellow eye. Evaluation for infectious,
      neoplastic, ischemic, and inflammatory disorders was unrevealing. High-dose
      corticosteroids appeared to stabilize his vision temporarily. Eventually he was
      diagnosed with papilledema in the setting of transverse venous sinus stenosis and
      dural arteriovenous fistula. His papilledema resolved, and his vision improved
      following stenting of the venous sinus stenosis and embolization of the fistula. 

PMID- 24913333
TI  - Targeting FANCD2 for therapy sensitization.

PMID- 24913332
TI  - Down-regulation of the expression of CCAAT/enhancer binding protein alpha gene in
      cervical squamous cell carcinoma.
AB  - BACKGROUND: Cervical carcinoma is the second most common cancer and is an
      important cause of death in women worldwide. CCAAT/enhancer binding proteins
      (C/EBPs) are a family of transcription factors that regulate cellular
      differentiation and proliferation in a variety of tissues. However, the role of
      C/EBPalpha gene in cervical cancer is still not clear. METHODS: We investigated
      the expression of C/EBPalpha gene in cervical squamous cell carcinoma. C/EBPalpha
      mRNA level was measured by real-time quantitative RT-PCR in cervical cancer
      tissues and their adjacent normal tissues. C/EBPalpha protein level was measured
      by immunohistochemistry. Methylation in the promoter of C/EBPalpha gene was
      detected by MALDI TOF MassARRAY. We transfected HeLa cells with C/EBPalpha
      expression vector. C/EBPalpha expression in HeLa cells was examined and HeLa cell
      proliferation was measured by MTT assay and HeLa cells migration was analyzed by
      matrigel-coated transwell migration assays. RESULTS: There were significant
      difference in C/EBPalpha protein expression between chronic cervicitis and
      cervical carcinoma (P < 0.001). CEBPalpha mRNA level was significantly lower in
      cervical cancer tissues than in normal cervical tissues (P < 0.01). Methylation
      of the promoter of CEBPalpha gene in CpG 5, CpG-14.15, CpG-19.20 were
      significantly higher in cervical cancer than in normal cervical tissues (P <
      0.05, P < 0.01, P < 0.05, respectively). CEBPalpha pcDNA3.1 construct transfected
      into HeLa cells inhibited cell proliferation and decreased cell migration.
      CONCLUSIONS: Our results indicate that reduced C/EBPalpha gene expression may
      play a role in the development of cervical squamous cell carcinoma.

PMID- 24913334
TI  - Neurodevelopmental delay with critical congenital heart disease is mainly from
      prenatal injury not infant cardiac surgery: current evidence based on a meta
      analysis of functional magnetic resonance imaging.
AB  - OBJECTIVE: No consensus has been reached regarding whether brain injury related
      to congenital heart disease (CHD) is caused by infant cardiac surgery and/or
      prenatal injury resulting from the CHD. We performed this meta-analysis to
      identify the likely cause of neurodevelopmental delay in CHD patients. METHODS:
      We carried out a literature search without language restriction in December 2013,
      retrieving records from PubMed, EMBASE, the Cochrane Library and the World Health
      Organization trials center, to identify studies applying functional magnetic
      resonance imaging (fMRI) evaluation of brain function before surgery and, in some
      cases, after surgery (both immediate term and short term postoperatively). The
      preoperative and postoperative fMRI results were extracted, and meta-analysis was
      performed using Revman 5.1.1 and STATA 11.0, according to the guidelines from the
      Cochrane review and MOOSE groups. RESULTS: The electronic search yielded 937
      citations. Full text was retrieved for 15 articles and eight articles (nine
      studies) were eligible for inclusion: six studies (n = 312 cases) with fMRI
      analysis before surgery and three (n = 36 cases) with complete perioperative fMRI
      analysis. The overall average diffusivity of CHD cases was significantly higher
      than that of controls, with a summarized standard (std) mean difference of 1.39
      (95% CI, 0.70-2.08), and the fractional anisotropy was lower in CHD cases, with a
      summarized mean difference of -1.43 (95% CI, -1.95 to -0.91). N-acetylaspartate
      (NAA)/choline (Cho) for the whole brain was significantly lower in CHD cases
      compared with healthy ones, while lactate/Cho was significantly higher in CHD
      cases. Immediate term postoperatively, significant changes in NAA/creatine and
      NAA/Cho, relative to preoperative values, were found. However, the difference did
      not persist at the short-term follow-up. CONCLUSION: This meta-analysis suggests
      that the delay in neurological development in newborns with CHD is due mainly to
      prenatal injury, and cardiac surgery might lead to mild brain injuries
      postoperatively, but fMRI shows recovery within a short period.

PMID- 24913335
TI  - Cognitive-behavioral therapy for irritable bowel syndrome: a meta-analysis.
AB  - OBJECTIVE: To establish whether cognitive behavioral therapy (CBT) improves the
      bowel symptoms, quality of life (QOL) and psychological states of irritable bowel
      syndrome (IBS) patients. METHODS: Randomized controlled trials (RCTs) of CBT for
      adult patients with IBS were searched by using PubMed, Scopus and Web of Science.
      The standardized mean difference (SMD) with 95% confidence intervals (CIs) of the
      evidence-based outcome measures of the IBS bowel symptoms, QOL and psychological
      states at post-treatment and follow-up was calculated. Prespecified subgroup
      analysis was performed. RESULTS: Eighteen RCTs satisfied our inclusion criteria.
      In the subgroup analyses, CBT was more effective in reducing IBS bowel symptoms,
      QOL and psychological states than waiting list controls at the end of the
      intervention and short-term follow-up. When compared with controls of basic
      support and medical treatment, the effect sizes were found to favor CBT for the
      improvement of IBS bowel symptoms at post-treatment and short-term follow-up, but
      CBT was not superior to controls in improving QOL and psychological states. When
      comparing CBT with other psychological controls, the effect sizes were almost non
      significant. CONCLUSIONS: For IBS patients, CBT was superior to waiting list,
      basic support or medical treatment at the end of treatment but not superior to
      other psychological treatments. The meta-analysis might be limited by the
      heterogeneities and small sample sizes of the included studies.

PMID- 24913336
TI  - Irritable bowel syndrome and symptom severity: evidence of negative attention
      bias, diminished vigour, and autonomic dysregulation.
AB  - OBJECTIVE: To determine if cognitive processing, and subjective and physiological
      responses to stress and relaxation differed between an irritable bowel syndrome
      (IBS) group and control group. How these variables relate to the severity of IBS
      symptoms was also determined. METHODS: Twenty-one IBS participants and 20
      controls provided cognitive (attention and processing), subjective (perceived
      stress and vigour), and physiological (heart rate, blood pressure, and skin
      conductance) data during a relaxation and stress phase. Logistic regression
      analyses determined which variables are related to the IBS group and hierarchical
      linear regression assessed how the variables are related to the severity of IBS
      symptoms. RESULTS: Subjective and cognitive factors (drowsiness at baseline,
      total vigour, and reduced Stroop colour-naming accuracy for negative words) are
      significantly related to IBS, chi2 (3, N=41)=23.67, p<.001, accurately
      categorising 85% of participants. IBS symptom severity was associated with both
      subjective (drowsiness at baseline and a smaller reduction in tiredness from
      relaxation to stress) and physiological (smaller increase in systolic blood
      pressure from baseline to stress phase and lower skin conductance at baseline)
      variables. This model predicted IBS severity, F (4, 16)=11.20, p<.001, and
      accounted for 74% of the variability in scores. CONCLUSIONS: A negative attention
      bias, which may be related to a negative self-schema, as well as perceived low
      vigour were important in categorising IBS. Low subjective vigour and reduced
      physiological reactivity to both relaxation and stress conditions were associated
      with IBS severity, suggestive of illness-related allostatic load.

PMID- 24913337
TI  - Adverse events and deterioration reported by participants in the PACE trial of
      therapies for chronic fatigue syndrome.
AB  - OBJECTIVE: Adverse events (AEs) are health related events, reported by
      participants in clinical trials. We describe AEs in the PACE trial of treatments
      for chronic fatigue syndrome (CFS) and baseline characteristics associated with
      them. METHODS: AEs were recorded on three occasions over one year in 641
      participants. We compared the numbers and nature of AEs between treatment arms of
      specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing
      therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy
      (GET). We examined associations with baseline measures by binary logistic
      regression analyses, and compared the proportions of participants who
      deteriorated by clinically important amounts. RESULTS: Serious adverse events and
      reactions were infrequent. Non-serious adverse events were common; the median
      (quartiles) number was 4 (2, 8) per participant, with no significant differences
      between treatments (P=.47). A greater number of NSAEs were associated with
      recruitment centre, and baseline physical symptom count, body mass index, and
      depressive disorder. Physical function deteriorated in 39 (25%) participants
      after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC
      (P<.001), with no significant differences in worsening fatigue. CONCLUSIONS: The
      numbers of adverse events did not differ significantly between trial treatments,
      but physical deterioration occurred most often after APT. The reporting of non
      serious adverse events may reflect the nature of the illness rather than the
      effect of treatments. Differences between centres suggest that both
      standardisation of ascertainment methods and training are important when
      collecting adverse event data.

PMID- 24913338
TI  - Mindfulness-based cognitive therapy (MBCT) for patients with medically
      unexplained symptoms: process of change.
AB  - BACKGROUND: A recent randomized controlled trial provided preliminary evidence
      for the effectiveness of mindfulness based cognitive therapy (MBCT) for the top
      10% frequent attenders in primary care with persistent medically unexplained
      symptoms (MUS). This qualitative study aims to explore working mechanisms and
      possible barriers of MBCT in this population. METHODS: Twelve participants of the
      trial were interviewed about their experiences. This was done before and after
      the MBCT course, and 12 months later. Written evaluations of participants and
      notes of participant observers were used for data-triangulation. RESULTS: In
      total, 35 qualitative interviews were conducted. MBCT initiated a process of
      change, starting with awareness of the present moment, the associated sensory
      experiences, thoughts and emotions and accepting rather than resisting these.
      Participants started to recognize their own behavioral patterns and change them,
      thus improving self-care. Self-compassion seemed to result from and facilitate
      this process. Main barriers were concurrent social problems and the inability or
      unwillingness to accept symptoms. CONCLUSIONS: MBCT can start a process of change
      in patients with persistent MUS. Awareness and acceptance of painful symptoms and
      emotions are key factors in this process. Change of unhelpful behavioral patterns
      and increased self-care and self-compassion can result from this process.

PMID- 24913340
TI  - Childhood trauma and dissociation in tertiary care patients with migraine and
      tension type headache: a controlled study.
AB  - OBJECTIVE: The aims of this study were: i) to compare the severity of somatoform
      and psychoform dissociation and childhood trauma among migraine patients, tension
      type headache patients (TTH), and healthy controls; and, ii) to identify any
      relationships between headache characteristics and dissociative symptoms and
      traumatic childhood experiences among tertiary care patients with headache.
      METHODS: The study sample consisted of 79 patients with migraine, 49 patients
      with TTH and 40 healthy controls. They completed the socio-demographic form,
      Childhood Trauma Questionnaire (CTQ), Dissociative Experiences Scale (DES), and
      the Somatoform Dissociation Questionnaire (SDQ). RESULTS: The average score for
      childhood emotional abuse was significantly higher in the TTH and migraine
      patients than in healthy controls; mean scores for emotional neglect and physical
      abuse were higher in TTH patients than healthy controls; and the total CTQ score
      was higher in TTH patients than in either migraine patients or healthy controls.
      Average DES scores were significantly higher in TTH patients versus migraine
      patients and controls; and SDQ scores were higher in both headache groups than in
      controls. Headache duration and severity were found to be significantly related
      to childhood abuse scores among migraine but not TTH patients. CONCLUSION: Our
      findings support the evidence of a relationship between childhood trauma and
      migraines, and suggest that childhood traumatic events are common and
      deleteriously effect migraine characteristics. Also our study suggests that
      childhood trauma may have a role in TTH. Significant differences in the DES and
      SDQ scores between groups may be explained by the differences in childhood trauma
      experiences.

PMID- 24913339
TI  - Individual variation in temporal relationships between stress and functional
      somatic symptoms.
AB  - OBJECTIVE: Medically unexplained or functional somatic symptoms (FSSs) constitute
      a major health problem because of their high prevalence and the suffering and
      disability they cause. Psychosocial stress is widely believed to be a
      precipitating or perpetuating factor, yet there is little empirical evidence to
      support this notion. Prior studies mainly focused on comparing groups, which has
      resulted in the obscuring of temporal complexity and individual differences. The
      aim of this study is to elucidate the relationship between stress and FSSs over
      time within individual patients. METHODS: Twenty patients (17 females, ages 29
      59) with multiple, persistent FSSs were included in the study. They used
      electronic diaries to report stress and FSSs twice daily over the course of 12
      weeks. For each individual data set, Vector autoregressive (VAR) modelling was
      used to investigate possible associations between daily average stress and FSSs
      scores. RESULTS: In six subjects (30%), an increase in stress was followed by an
      increase in one or more FSSs. In three subjects (15%), an increase in FSSs was
      followed by an increase in stress. Additionally, negative and mixed associations
      were found. Only two subjects (10%) showed no cross-lagged association between
      stress and FSSs in either direction. We did not find specific types of symptoms
      to be more stress-related than others. CONCLUSION: Although stress does not seem
      to be a universal predictor of FSSs, an increase in stress precedes an increase
      in symptoms in some individuals. Identifying these individuals using time-series
      analysis might contribute to a more patient-tailored treatment.

PMID- 24913341
TI  - Behavioral health mediators of the link between posttraumatic stress disorder and
      dyslipidemia.
AB  - OBJECTIVES: Posttraumatic stress disorder (PTSD) has been linked to dyslipidemia,
      which is a major risk factor for coronary artery disease. Although this link is
      thought to reflect response to heightened stress, behavioral health risks,
      including smoking, alcohol dependence, and poor sleep quality, may mediate the
      relationship between PTSD and dyslipidemia. METHODS: To test this hypothesis,
      serum lipid levels were collected from 220 young adults (18-39 years old), 103 of
      whom were diagnosed with PTSD. RESULTS: PTSD and associated depressive symptoms
      were negatively related to high-density lipoprotein cholesterol (HDL-C), p=.04,
      and positively related to triglyceride (TG) levels, p=.04. Both associations were
      mediated by cigarette consumption and poor sleep quality, the latter of which
      accounted for 83% and 93% of the effect of PTSD and depression on HDL-C and TG,
      respectively. CONCLUSIONS: These results complement recent findings highlighting
      the prominence of health behaviors in linking PTSD with cardiovascular risk.

PMID- 24913343
TI  - Cost utility analysis of a collaborative stepped care intervention for panic and
      generalized anxiety disorders in primary care.
AB  - OBJECTIVE: Generalized anxiety and panic disorders are a burden on the society
      because they are costly and have a significant adverse effect on quality of life.
      The aim of this study was to evaluate the cost-utility of a collaborative stepped
      care intervention for panic disorder and generalized anxiety disorder in primary
      care compared to care as usual from a societal perspective. METHODS: The design
      of the study was a two armed cluster randomized controlled trial. In total 43
      primary care practices in the Netherlands participated in the study. Eventually,
      180 patients were included (114 collaborative stepped care, 66 care as usual).
      Baseline measures and follow-up measures (3, 6, 9 and 12 months) were assessed
      using questionnaires. We applied the TiC-P, the SF-HQL and the EQ-5D respectively
      measuring health care utilization, production losses and health related quality
      of life. RESULTS: The average annual direct medical costs in the collaborative
      stepped care group were 1854 Euro (95% C.I., 1726 to 1986) compared to ?1503 (95%
      C.I., 1374 to 1664) in the care as usual group. The average quality of life years
      (QALYs) gained was 0.05 higher in the collaborative stepped care group, leading
      to an incremental cost effectiveness ratio (ICER) of 6965 Euro per QALY.
      Inclusion of the productivity costs, consequently reflecting the full societal
      costs, decreased the ratio even more. CONCLUSION: The study showed that
      collaborative stepped care was a cost effective intervention for panic disorder
      and generalized anxiety disorder and was even dominant when a societal
      perspective was taken. TRIAL REGISTRATION: trialregister.nl, Netherlands Trial
      Register NTR107.

PMID- 24913342
TI  - Attributional styles and stress-related atherogenic plasma lipid reactivity in
      essential hypertension.
AB  - OBJECTIVE: Hypertension and an atherogenic lipid profile are known risk factors
      for coronary heart disease (CHD). Hypertensives show greater changes in
      atherogenic plasma lipids to acute stress than normotensives. In this study, we
      investigated whether attribution of failure is associated with lipid stress
      reactivity in hypertensive compared with normotensive men. METHODS: 18
      normotensive and 17 hypertensive men (mean+/-SEM; 45+/-2.2 years) underwent an
      acute standardized psychosocial stress task that can be viewed as a situation of
      experimentally induced failure. We assessed external-stable (ES), external
      variable (EV), internal-stable (IS), and internal-variable (IV) attribution of
      failure and psychological control variables (i.e. extent of depression and
      neuroticism). Moreover, total cholesterol (TC), low-density-lipoprotein
      cholesterol (LDL-C), and norepinephrine were measured immediately before and
      several times after stress. RESULTS: ES moderated TC- and LDL-C-stress reactivity
      in hypertensives as compared to normotensives (interaction mean arterial pressure
      [MAP]-by-ES for TC: F=3.71, p=.015; for LDL-C: F=3.61, p=.016). TC and LDL-C
      levels were highest in hypertensives with low ES immediately after stress
      (p<=.039). In contrast, hypertensives with high ES did not differ from
      normotensives in TC and LDL-C immediately after stress (p's>.28). Controlling for
      norepinephrine, depression, and neuroticism in addition to age and BMI did not
      significantly change results. There were no significant associations between
      lipid baseline levels or aggregated lipid secretion and IS, IV, or EV (p's>.23).
      CONCLUSION: Our data suggest that ES may independently protect from elevated
      lipid stress reactivity in hypertensive individuals. ES thus might be a
      protective factor against CHD in hypertension.

PMID- 24913344
TI  - Turning the pink cloud grey: dampening of positive affect predicts postpartum
      depressive symptoms.
AB  - OBJECTIVE: Maladaptive response styles to negative affect have been shown to be
      associated with prospective (postpartum) depression. Whether maladaptive styles
      to positive affect are also critically involved is understudied, even though
      anhedonia (a correlate of low positive affectivity) is a cardinal symptom of
      depression. The present study is the first to investigate the predictive value of
      cognitive response styles to both negative (depressive rumination) and positive
      affect (dampening) for postpartum depressive symptoms. METHODS: During the third
      trimester of pregnancy, 210 women completed self-report instruments assessing
      depression (symptom severity and current and/or past episodes) and scales gauging
      the presence of depressive rumination and dampening. Of these women, 187 were
      retained for postpartum follow-up, with depressive symptoms being reassessed at
      12 (n=171) and 24 (n=176) weeks after delivery. RESULTS: Regression analyses
      showed that higher levels of dampening of positive affect during pregnancy
      predicted higher levels of depressive symptoms at 12 and 24 weeks postpartum,
      irrespective of initial symptom severity, past history of depression and levels
      of rumination to negative affect. Prepartum trait levels of rumination, however,
      did not predict postpartum symptomatology when controlled for baseline symptoms
      and history of major depressive episode(s). CONCLUSIONS: The results of this
      investigation suggest that the way women cognitively respond to positive affect
      contributes perhaps even more to the development of postpartum depression than
      maladaptive response styles to negative affect.

PMID- 24913345
TI  - A seven day actigraphy-based study of rumination and sleep disturbance among
      young adults with depressive symptoms.
AB  - OBJECTIVES: Trait ruminators exhibit significantly higher levels of sleep
      disturbance than those without this cognitive vulnerability. However, support for
      the sleep disruptive effects of state rumination, especially in the pre-sleep
      period, is rare, and hindered by methodological drawbacks such as self-report and
      single night assays of sleep. Finally, despite the pervasiveness of the
      ruminative response style among individuals with depression, the association
      between rumination and sleep disturbance has not been explored in this
      population. The present study employed a week-long daily sampling approach to
      examine the effects of naturally occurring pre-sleep rumination on self-reported
      and actigraphy-based sleep among individuals with high depressive symptomatology.
      METHODS: Forty-two university students (19.6+/-3.2 yo;73.8% female), all of whom
      reported at least moderate levels of depressive symptoms, completed a short
      questionnaire after waking each morning for seven days. On this questionnaire,
      they self-reported sleep indices from the previous night and levels of engagement
      in pre-sleep rumination. Sleep was also monitored throughout this period via
      wrist actigraphy. Hierarchical-linear-modeling was used to examine the
      association between nightly rumination and sleep. RESULTS: Nightly variations in
      pre-sleep rumination were predictive of significantly longer actigraphy- and
      diary-based sleep onset latency (SOL). Notably, a 1 SD increase on the pre-sleep
      rumination scale was associated with an approximately 7 minute increase in
      actigraphy-based SOL, even after controlling for baseline sleep disturbance and
      depressive symptoms. CONCLUSIONS: These data offer compelling evidence for the
      impact of pre-sleep rumination on sleep onset, providing insight into one
      potential mechanism that triggers sleep disturbance among individuals with
      depressive symptoms.

PMID- 24913346
TI  - Influence of the BDNF Val66Met polymorphism on coping response to stress in
      patients with advanced gastric cancer.
AB  - OBJECTIVE: Coping with cancer is an important determinant of psychological
      morbidity, quality of life, and treatment adherence in cancer patients. The aim
      of this study was to elucidate the association between the brain-derived
      neurotrophic factor (BDNF) Val66Met polymorphism and coping response to stress in
      patients diagnosed with advanced gastric cancer. METHODS: Ninety-one subjects (60
      males, 31 females) recently diagnosed with advanced gastric cancer were
      recruited. Coping style and distress level were examined using the Mini-Mental
      Adjustment to Cancer (Mini-MAC) scale and Hospital Anxiety and Depression Scale,
      and genotyping was evaluated. To examine the temporal stability of the Mini-MAC
      scores, a 6-week follow-up evaluation was conducted in 72 patients, after
      completion of two chemotherapy cycles. RESULTS: Coping style to cancer
      significantly differed between the Met carriers of BDNF Val66Met and the Val/Val
      homozygotes. The Met carriers were significantly more anxious than the Val/Val
      homozygotes. CONCLUSION: The present findings suggest that the BDNF Val66Met
      polymorphism may be involved in individual coping responses to cancer. The Met
      allele of BDNF Val66Met may be predictive of an anxious coping style in patients
      with advanced cancer.

PMID- 24913347
TI  - Mindfulness-based cognitive therapy for people with diabetes and emotional
      problems: long-term follow-up findings from the DiaMind randomized controlled
      trial.
AB  - OBJECTIVE: The DiaMind trial showed beneficial immediate effects of mindfulness
      based cognitive therapy (MBCT) on emotional distress, but not on diabetes
      distress and HbA1c. The aim of the present report was to examine if the effects
      would be sustained after six month follow-up. METHODS: In the DiaMind trial, 139
      outpatients with diabetes (type-I or type-II) and a lowered level of emotional
      well-being were randomized into MBCT (n=70) or a waiting list with treatment as
      usual (TAU: n=69). Primary outcomes were perceived stress, anxiety and depressive
      symptoms, and diabetes distress. Secondary outcomes were, among others, health
      status, and glycemic control (HbA1c). RESULTS: Compared to TAU, MBCT showed
      sustained reductions at follow-up in perceived stress (p<.001, d=.76), anxiety
      (p<.001, assessed by HADS d=.83; assessed by POMS d=.92), and HADS depressive
      symptoms (p=.004, d=.51), but not POMS depressive symptoms when using Bonferroni
      correction for multiple testing (p=.016, d=.48). No significant between-group
      effect was found on diabetes distress and HbA1c. CONCLUSION: This study showed
      sustained benefits of MBCT six months after the intervention on emotional
      distress in people with diabetes and a lowered level of emotional well-being.
      TRIAL REGISTRATION: Dutch Trial Register NTR2145, http://www.trialregister.nl.

PMID- 24913348
TI  - Evaluating the manufacturability and combustion behaviors of sludge-derived fuel
      briquettes.
AB  - Based on the physical and chemical properties as well as calorific values of pulp
      sludge and textile sludge, this study investigates the differences between
      manufacturability, relationship between extrusion pressure and formability, as
      well as stability and combustion behaviors of extruded sludge-derived fuel
      briquettes (ESBB) and cemented sludge-derived fuel blocks (CSBB). The optimum
      proportion and relevant usage ESBB policies are proposed as well. Experimental
      results indicate that a large amount of water can be saved during the ESBB
      manufacturing process. Additionally, energy consumption decreases during the
      drying process. ESBB also has a more compact structure than that of CSBB, and its
      mean penetration loading is approximately 18.7 times higher as well. Moreover,
      the flame temperature of ESBB (624-968 degrees C) is significantly higher than
      that of CSBB (393-517 degrees C). Also, the dry bulk density and moisture regain
      of ESBB is significantly related to the penetration loading. Furthermore, the
      optimum mix proportion of ESBB is co-determined by the formability of pulp sludge
      and the calorific values of textile sludge. While considering the specific
      conditions (including formability, stability and calorific values), the
      recommended mix proportion for ESBB is PS50TS50. 

PMID- 24913349
TI  - The incidence of venous thromboembolism in commercial airline pilots: a cohort
      study of 2630 pilots.
AB  - BACKGROUND: Airline pilots may be at increased risk of venous thromboembolism
      (VTE) because air travel has recently been established as a risk factor for VTE.
      OBJECTIVES: The aim of this study was to assess the risk of VTE in a cohort of
      Dutch airline pilots. PATIENTS/METHODS: Airline pilots who had been active
      members of the Dutch aviation society (VNV) were questioned for the occurrence of
      VTE, presence of risk factors for VTE and number of flight hours per year and
      rank. Incidence rates among pilots were compared with those of the general Dutch
      population and with a population of frequently flying employees of multinational
      organizations. RESULTS AND CONCLUSIONS: A total of 2630 male pilots were followed
      up for a total of 20420 person-years (py). Six venous thromboses were reported,
      yielding an incidence rate of 0.3 per 1000 py. The standardized morbidity ratio,
      comparing these pilots with the general Dutch population adjusted for age, was
      0.8. Compared with the international employee cohort, the standardized morbidity
      ratio was 0.7 when all employees were included and 0.6 when only the frequently
      travelling employees were included. The incidence rate did not increase with
      number of flight hours per year and did not clearly vary by rank. We conclude
      that the risk of VTE is not increased amongst airline pilots.

PMID- 24913351
TI  - Impact of exercise on pro inflammatory cytokine levels and epigenetic modulations
      of tumor-competitive lymphocytes in Non-Hodgkin-Lymphoma patients-randomized
      controlled trial.
AB  - INTRODUCTION: Physical activity is associated with decreased cancer (recurrence)
      risk and a reduction in treatment-specific side effects. Exercise modulates
      cytokine expression and shows beneficial effects on cancer patients' immune
      system. We investigated the following: (i) whether Non-Hodgkin-Lymphoma patients
      have increased serum macrophage migration inhibiting factor (MIF) and Interleukin
      6 (IL-6) levels after immunochemotherapy; (ii) whether physical activity
      influences cytokine serum levels; and (iii) whether serum cytokine levels are
      associated with histone modifications in tumor-competitive immune cells. METHODS:
      Thirty patients and 10 healthy controls were randomised into an intervention and
      a control group. Participants of the intervention group exercised once for 30 min
      at moderate intensity on a bicycle ergometer. Blood samples were collected twice,
      before and after the intervention. MIF and IL-6 serum concentrations were
      detected by ELISA. Natural killer cells and CD8(+) T-lymphocytes were isolated by
      magnetic labeled cell sorting. Isolated cells were stained and analyzed for
      global histone acetylation at histone 4, lysine 5 and histone three, lysine 9.
      RESULTS: Patients showed higher serum MIF and IL-6 baseline levels, and reduced
      NK-cell histone acetylation, indicating a reduced transcriptional activity of
      tumor-competitive lymphocytes. Changes in MIF correlated with altered NK-cell
      histone acetylation, leading to the hypothesis that MIF impacts NK-cells via
      epigenetic modifications. Further, the exercise intervention was associated with
      an increase in IL-6 and CD8(+) T-lymphocyte histone acetylation. CONCLUSIONS: We
      conclude that exercise induces changes in cytokine levels, thereby possibly
      affecting epigenetic patterns and activity of tumor-competitive lymphocytes.

PMID- 24913352
TI  - Treatment of spasmodic dysphonia with a neuromodulating electrical implant.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the feasibility of an implantable
      electrical stimulation device to treat spasmodic dysphonia (SD) by
      neuromodulation of the muscle spindle gamma loop. STUDY DESIGN: Prospective case
      series. METHOD: Five subjects underwent daily stimulation of the left
      thyroarytenoid muscle (TA) below the level of alpha-motor neuron activation
      (AMNA) for 5 consecutive days. Professional and patient voice evaluations were
      performed. Transcartilagenous placement of an implantable stimulation device lead
      was investigated in anesthetized porcine and cadaveric human models. RESULTS:
      Three of 5 subjects improved in all categories of evaluation. One subject
      improved in three of four categories. These four subjects described significant
      carryover of effect after treatment. The fifth subject evidenced improvement
      until contracting an upper respiratory infection on day 3. Transcartilagenous
      electrode placement into the porcine TA with muscle stimulation was successful.
      The electrode lead was passed from the cadaveric larynx to the mastoid tip in the
      subplatysma layer with an absence of tension. CONCLUSION: The symptoms of SD
      improve after electrical stimulation of the TA at levels below AMNA. This is
      likely through neuromodulation of the muscle spindle gamma loop. Implantation of
      an electrode into the TA with a postauricular implanted stimulator is feasible
      with modifications of an already existing device. With further investigation,
      such a device has the potential to deliver an alternative treatment for SD. LEVEL
      OF EVIDENCE: 4.

PMID- 24913350
TI  - The node of Ranvier in CNS pathology.
AB  - Healthy nodes of Ranvier are crucial for action potential propagation along
      myelinated axons, both in the central and in the peripheral nervous system.
      Surprisingly, the node of Ranvier has often been neglected when describing CNS
      disorders, with most pathologies classified simply as being due to neuronal
      defects in the grey matter or due to oligodendrocyte damage in the white matter.
      However, recent studies have highlighted changes that occur in pathological
      conditions at the node of Ranvier, and at the associated paranodal and
      juxtaparanodal regions where neurons and myelinating glial cells interact.
      Lengthening of the node of Ranvier, failure of the electrically resistive seal
      between the myelin and the axon at the paranode, and retraction of myelin to
      expose voltage-gated K(+) channels in the juxtaparanode, may contribute to
      altering the function of myelinated axons in a wide range of diseases, including
      stroke, spinal cord injury and multiple sclerosis. Here, we review the principles
      by which the node of Ranvier operates and its molecular structure, and thus
      explain how defects at the node and paranode contribute to neurological
      disorders. 

PMID- 24913353
TI  - Outcome of delayed resuscitation bundle achievement in emergency department
      patients with septic shock.
AB  - The aim of this study was to assess whether delayed resuscitation bundle
      compliance from 6 to 12 h after a diagnosis of septic shock has an impact upon 28
      day mortality. A prospective observational study on consecutive adult patients
      with septic shock was performed in the Emergency Department (ED) of a tertiary
      care university-affiliated hospital between January 2010 and July 2012.
      Compliance with the resuscitation bundle was assessed at 6 and 12 h after a
      septic shock diagnosis (time 0). Patients were divided into three groups: early
      compliance (<=6 h), delayed compliance (>6 but <=12 h), and non-compliance (>12
      h). The 28-day mortality was compared among the groups. A total of 332 patients
      were included, with an overall 28-day mortality of 17.2%. The mean age was 63.9
      years; 57.8% were men. Early compliance was achieved in 195 patients (58.7%),
      delayed compliance in 59 patients (19.8%), and non-compliance in 78 patients
      (23.5%). The groups did not differ in baseline sequential organ failure
      assessment illness severity. However, the non-compliance group had a
      significantly higher mortality (29.5%) than the delayed-compliance (13.6%) and
      early-compliance (13.3%) groups (p = 0.04). Delayed compliance was associated
      with a lower mortality risk than non-compliance (adjusted odds ratio 0.32, 95%
      confidence interval: 0.13-0.82, p = 0.02). In conclusion, if bundle therapy be
      started at the time of presentation, the outcome of delayed resuscitation bundle
      compliance within 12 h is same as that of early resuscitation bundle compliance
      within 6 h, and these are better than that of the patients who had late or no
      compliance.

PMID- 24913354
TI  - Percutaneous closure of large VSD using a home-made fenestrated atrial septal
      occluder in 18-year-old with pulmonary hypertension.
AB  - BACKGROUND: Hemodynamically significant muscular ventricular septal defects in
      children after the infantile period are a rare occurrence and ideal for
      transcatheter closure. In cases of severe concomitant pulmonary hypertension, it
      may be necessary to fenestrate the device. In this report, we present an 18-year
      old patient with a large mid-trabecular ventricular septal defect and severe
      pulmonary hypertension that underwent percutaneous closure of the defect with a
      home-made fenestrated atrial septal occluder. CASE PRESENTATION: An 18-year-old
      female patient referred to us with complaints of dyspnea (NYHA score of 2-3).
      Physical examination revealed an apical rumble and a harsh second heart sound.
      Echocardiographic examination revealed a large mid-trabecular ventricular septal
      defect with bidirectional shunt and the widest diameter measuring 22 mm on 2D
      echocardiography. Left and right heart cavities were enlarged. Before and after
      the vasoreactivity test performed during cardiac catheterization, average aortic
      pressure was 65 -> 86 mmHg, average pulmonary artery pressure: 58 -> 73 mmHg,
      Qp/Qs: 1.6 -> 3.2, PVR: 4.6 -> 4.3 Wood/U/m2 and PVR/SVR: 0.5 -> 0.2. On left
      ventricular angiocardiogram, the largest end-diastolic defect diameter was 21 mm.
      The closure procedure was performed with transthoracic echocardiographic
      guidance, using a 24 mm Cera septal occluder and a 14 F sheath dilator to make a
      4.5-5 mm opening. Measured immediately after the procedure and during cardiac
      catheterization one month later, average aortic pressure was 75 -> 75 mmHg,
      average pulmonary artery pressure: 66 -> 30 mmHg, Qp/Qs 1.5 -> 1.4, PVR: 4.4 ->
      2.9 Wood/U/m2 and PVR/SVR: 0.4 -> 0.2. Transthoracic echocardiographic
      examination performed 24 hours after the procedure showed a max 35-40 mmHg
      gradient between the left and right ventricles through the fenestration. After
      the procedure, we observed sporadic early ventricular systoles and a nodal rhythm
      disorder that started after approximately 12 hours and spontaneously reverted to
      normal 9 days later. CONCLUSION: In patients with large ventricular septal
      defects, large atrial septal occluders may be used. In cases with risk of
      pulmonary vascular disease, a safer option would be to close the defect using a
      manually fenestrated device.

PMID- 24913356
TI  - Rice fortification: a comparative analysis in mandated settings.
AB  - Legal mandates can play an important role in the success of rice fortification
      programs that involve the private sector. However, merely enacting mandatory
      legislation does not guarantee success; it requires a coordinated,
      multidimensional cross-sector effort that addresses stewardship, develops an
      appropriate rice fortification technology, enables sustainable production and
      distribution channels through a range of private-sector players, ensures quality,
      generates consumer demand, and monitors progress. Furthermore, economic
      sustainability must be built into the supply chain and distribution network to
      enable the program to outlast government administrations and/or time-limited
      funding. Hence, mandates can serve as valuable long-term enablers of cross-sector
      mobilization and collaboration and as catalysts of civil society engagement in
      and ownership of fortification programs. This paper compares the rice
      fortification experiences of Costa Rica and the Philippines--two countries with
      mandates, yet distinctly different industry landscapes. Costa Rica has achieved
      national success through strong government stewardship and active market
      development--key elements of success regardless of industry structure. With a
      comparatively more diffuse rice industry structure, the Philippines has also had
      success in limited geographies where key stakeholders have played an active role
      in market development. A comparative analysis provides lessons that may be
      relevant to other rice fortification programs.

PMID- 24913355
TI  - Expression and Y435-phosphorylation of Abelson interactor 1 (Abi1) promotes
      tumour cell adhesion, extracellular matrix degradation and invasion by colorectal
      carcinoma cells.
AB  - BACKGROUND: The Abelson tyrosine kinase (c-Abl) inhibitor STI571 (Glivec(r)) has
      been shown to effectively inhibit colorectal cancer cell migration and invasion.
      The c-Abl substrate abelson interactor 1 (Abi1) is a key regulator of actin
      reorganization and upregulated in colorectal carcinoma. The specific role of Abi1
      in relation to extracellular matrix degradation and effects of targeting Abi1
      phosphorylation have not yet been examined. Here, we investigated the role of
      Abi1 in relation to invasive properties in colorectal cancer. METHODS AND
      RESULTS: In 56 primary human colorectal carcinoma samples, we found
      overexpression of Abi1 in 39% at the invasive edge of the tumour, associated with
      an infiltrative phenotype and high-grade tumour cell budding (p = 0.001). To
      explore the role of Abi1 in vitro, we employed the Abi1 expressing and KRAS
      mutated CHD1 model and performed matrix degradation assays that showed Abi1
      localization at specific sites of matrix degradation. Moreover, quantification of
      matrix dissolution demonstrated suppression after RNAi knockdown of Abi1 by 95%
      (p = 0.001). Importantly, treatment with STI571 did abolish Abi1 Y435
      phosphorylation, suppressed the matrix dissolution, decreased fibronectin
      attachment, and suppressed cell invasion through reconstituted extracellular
      matrix. CONCLUSION: Our data indicate that phosphorylated Abi1 contributes to the
      invasive properties of colorectal cancer.

PMID- 24913357
TI  - Single institution and statewide performance of ultrasound in diagnosing
      appendicitis in pregnancy.
AB  - OBJECTIVE: Assess the performance of ultrasound (US) in pregnant patients
      presenting with acute abdominal pain concerning for appendicitis. METHODS:
      Descriptive analysis of pregnant patients who underwent an US for acute abdominal
      pain over a 6-year period using data from a statewide quality improvement
      collaborative and a single center. RESULTS: Statewide, 131 pregnant patients
      underwent an appendectomy and 85% had an US. In our single-center case series, 49
      pregnant patients underwent an US for acute abdominal pain and four patients had
      appendicitis (8%). Of those, three were definitively diagnosed with US. The
      appendix was visualized by US in five patients (3 appendicitis/2 normal). Mean
      gestational age was 11 weeks for visualization of the appendix versus 20 weeks
      for non-visualization (p < 0.001). Concordance between US and pathology was
      similar statewide and at our institution (43%). CONCLUSIONS: US appears to play a
      central role in the evaluation of appendicitis in pregnant women, especially in
      the first trimester, and often contributes to definitive disposition. US
      performed less well in excluding appendicitis; however, in certain clinical
      settings, providers appeared to trust US findings. From these results, we
      developed a multidisciplinary imaging pathway for pregnant patients who present
      with acute abdominal pain concerning for appendicitis.

PMID- 24913358
TI  - Qualitative analysis of barriers and facilitators encountered by HIV patients in
      an ART adherence programme.
AB  - BACKGROUND: Medication adherence is a complex, dynamic and changing behaviour
      that is affected by a variety of factors, including the patient's beliefs and
      life circumstances. Studies have highlighted barriers to medication adherence
      (e.g., unmanaged side effects or a lack of social support), as well as
      facilitators of medication adherence (e.g., technical simplicity of treatment and
      psychological acceptance of the disease). Since August 2004, in Lausanne
      (Switzerland), physicians have referred patients who are either experiencing or
      are at risk of experiencing problems with their HIV antiretroviral treatment
      (ART) to a routine interdisciplinary ART adherence programme. This programme
      consists of multifactorial intervention including electronic drug monitoring
      (MEMSTM). OBJECTIVE: This study's objective was to identify the barriers and
      facilitators encountered by HIV patients with suboptimal medication adherence
      (<=90 % adherence over the study period). SETTING: The community pharmacy of the
      Department of Ambulatory Care and Community Medicine in Lausanne (Switzerland).
      METHOD: The study consisted of a retrospective, qualitative, thematic content
      analysis of pharmacists' notes that were taken during semi-structured interviews
      with patients and conducted as part of the ART adherence programme between August
      2004 and May 2008. MAIN OUTCOME MEASURE: Barriers and facilitators encountered by
      HIV patients. RESULTS: Barriers to and facilitators of adherence were identified
      for the 17 included patients. These factors fell into three main categories: (1)
      cognitive, emotional and motivational; (2) environmental, organisational and
      social; and (3) treatment and disease. CONCLUSION: The pharmacists' notes
      revealed that diverse barriers and facilitators were discussed during medication
      adherence interviews. Indeed, the results showed that the 17 non-adherent
      patients encountered barriers and benefited from facilitators. Therefore,
      pharmacists should inquire about all factors, regardless of whether they have a
      negative or a positive impact on medication adherence, and should consider all
      dimensions of patient adherence. The simultaneous strengthening of facilitators
      and better management of barriers may allow healthcare providers to tailor care
      to a patient's specific needs and support each individual patient in improving
      his medication-related behaviour.

PMID- 24913359
TI  - Retrospective analysis of the risk factors for linezolid-induced thrombocytopenia
      in adult Japanese patients.
AB  - BACKGROUND: Thrombocytopenia is a major side effect of linezolid therapy.
      However, there are few reports about the risk factors for linezolid-induced
      thrombocytopenia. OBJECTIVE: The aim of this study is to evaluate the risk
      factors for thrombocytopenia in patients who undergo linezolid therapy. SETTING:
      Aomori Prefectural Central Hospital in Japan, a tertiary 695 beds hospital.
      METHOD: A retrospective review was performed using the hospital's medical
      records. From January 2010 to August 2012, 75 adult patients who received
      linezolid therapy were enrolled in this study. MAIN OUTCOME MEASURE: Linezolid
      induced thrombocytopenia was defined as a decrease in the patient's platelet
      count to <10 * 104/MUL or a reduction of >=30 % from their baseline value. Odds
      ratios (OR) for thrombocytopenia were analyzed using multivariate stepwise
      logistic regression analysis. RESULTS: Thrombocytopenia occurred in 29 patients
      (38.6 %), seven of whom required platelet transfusions. The patients who
      developed thrombocytopenia were significantly older, displayed a significantly
      higher frequency of renal insufficiency, and received linezolid therapy for
      significantly longer than the patients without thrombocytopenia. Stepwise
      logistic regression analysis suggested that receiving linezolid therapy for >=14
      days was a significant risk factor for thrombocytopenia [OR 13.3, 95 % confidence
      interval (CI) 3.2-55.6, p < 0.01], whereas the creatinine clearance rate
      exhibited a significant negative correlation with the incidence of the condition
      [OR 0.98, 95 % CI 0.96-0.99, p = 0.037]. The incidence of thrombocytopenia among
      the patients who demonstrated creatinine clearance rates of <30 mL/min was 60 %
      (12/20), which was significantly higher than that observed among the patients who
      displayed creatinine clearance rates of more than 60 mL/min (26.4 %, 9/34, p =
      0.014). CONCLUSION: Receiving linezolid therapy for >=14 days and a low
      creatinine clearance rate were suggested to be risk factors for linezolid-induced
      thrombocytopenia. The platelet counts of patients with these risk factors should
      be closely monitored.

PMID- 24913360
TI  - Characterization of Sr9h, a wheat stem rust resistance allele effective to Ug99.
AB  - KEY MESSAGE: Wheat stem rust resistance gene SrWeb is an allele at the Sr9 locus
      that confers resistance to Ug99. Race TTKSK (Ug99) of Puccinia graminis f. sp.
      tritici, the causal fungus of stem rust, threatens global wheat production
      because of its broad virulence to current wheat cultivars. A recently identified
      Ug99 resistance gene from cultivar Webster, temporarily designated as SrWeb,
      mapped near the stem rust resistance gene locus Sr9. We determined that SrWeb is
      also present in Ug99 resistant cultivar Gabo 56 by comparative mapping and an
      allelism test. Analysis of resistance in a population segregating for both Sr9e
      and SrWeb demonstrated that SrWeb is an allele at the Sr9 locus, which
      subsequently was designated as Sr9h. Webster and Gabo 56 were susceptible to the
      Ug99-related race TTKSF+ from South Africa. Race TTKSF+ possesses unique
      virulence to uncharacterized Ug99 resistance in cultivar Matlabas. This result
      validated that resistance to Ug99 in Webster and Gabo 56 is conferred by the same
      gene: Sr9h. The emergence of pathogen virulence to several resistance genes that
      are effective to the original Ug99 race TTKSK, including Sr9h, suggests that
      resistance genes should be used in combinations in order to increase resistance
      durability.

PMID- 24913361
TI  - Mitochondrial atp9 genes from petaloid male-sterile and male-fertile carrots
      differ in their status of heteroplasmy, recombination involvement, post
      transcriptional processing as well as accumulation of RNA and protein product.
AB  - KEY MESSAGE: Petaloid cytoplasmic male-sterile carrots exhibit overexpression of
      the mitochondrial atp9 genes which is associated with specific features in
      organization and expression of these sequences. In carrots, the Sp-cytoplasm
      causes transformation of stamens into petal-like organs, while plants carrying
      normal N-cytoplasm exhibit normal flower morphology. Our work was aimed at
      characterization of distinct features both cytoplasms display with respect to
      organization and expression of the mitochondrial atp9 genes. We show that two
      carrot atp9 genes, previously reported as cytoplasm-specific, in fact occur in
      heteroplasmic condition. In the Sp-cytoplasm the atp9-1 version dominates over
      atp9-3, while in N-cytoplasmic plants this proportion is reversed. Herein, we
      also indicate the presence and recombination activity of a 130-/172-bp sequence
      repeat which likely shaped the present organization of carrot atp9 loci.
      Furthermore, cDNA sequence examination revealed that the atp9 open reading frames
      (ORFs) were C to U edited in 4 nucleotide positions. One of the editing events
      turns a glutamine triplet into the stop codon, thereby equalizing ORFs of atp9-1
      and atp9-3. A certain fraction of partially edited molecules was identified-they
      all represented the atp9-3 sequence. In either Sp- or N-cytoplasmic plants
      multiple 5' transcript termini were observed. Of these, the ones mapping more
      distantly from the atp9 ORF were more pronounced in case of petaloid accessions.
      It was also shown that despite comparable copy number of the genomic atp9
      sequences, the level of the respective mRNAs was approximately 3 times higher in
      case of petaloid carrots. The latter fact corresponded to the elevated content of
      the ATP9 protein in plants carrying Sp-cytoplasm. The semi-fertile phenotype of
      such plants is associated with a drop in ATP9 accumulation.

PMID- 24913363
TI  - Fine mapping of a dominant thermo-sensitive genic male sterility gene (BntsMs) in
      rapeseed (Brassica napus) with AFLP- and Brassica rapa-derived PCR markers.
AB  - KEY MESSAGE: A new thermo-sensitive dominant genic male sterility (TSDGMS) line
      of Brassica napus was found and mapped in this paper. Our result will greatly
      accelerate the map-based cloning of the BntsMs gene. TE5A is a thermo-sensitive
      dominant genic male sterility line originating from spontaneous mutation of the
      inbred line TE5 in Brassica napus and provides a promising system for the
      development of hybrid cultivars. Genetic analysis has revealed that the BntsMs
      mutant is controlled by a single, dominant gene. Here, we describe the fine
      mapping of BntsMs using amplified fragment length polymorphism (AFLP) and intron
      polymorphism (IP) methodologies. We screened 1,024 primer combinations and then
      identified five AFLP markers linked to the BntsMs gene, two of which were
      successfully converted into sequence-characterised amplified region (SCAR)
      markers. The linkage of the markers was identified by analysing a large BC2
      population of 700 recessive-fertility individuals. Two SCAR markers were found in
      the flanking region of the BntsMs gene at distance of 3.5 and 4.8 cm. Based on
      sequence information from the previously screened AFLP markers and on genome
      organisation comparisons of the A genome of Brassica rapa and Arabidopsis, seven
      IP markers linked to the BntsMs gene were developed. By analysing the 700
      recessive-fertility individuals, two IP markers, IP004 and IP470, were localised
      to the flanking region of the BntsMs gene at a distance of 0.3 and 0.2 cm,
      respectively. A comparison of the B. rapa and Arabidopsis genomes revealed 27
      genes of B. rapa in the flanking region of these two IP markers. It is likely
      that the molecular markers developed from these investigations will greatly
      accelerate the positional cloning of the BntsMs gene.

PMID- 24913365
TI  - Aspects of trapping efficiency and matrix effects in the development of a
      restricted-access-media-based trap-and-elute liquid chromatography with mass
      spectrometry method.
AB  - Online restricted access media with liquid chromatography and tandem mass
      spectrometry for the direct analysis of small molecules in biological fluids
      represents an interesting alternative to time-demanding traditional sample
      preparation techniques. In this study, important considerations concerning the
      development of a restricted access media with liquid chromatography and tandem
      mass spectrometry method for the analysis of dansylated estrogens in biological
      matrix are presented. Parameters influencing peak tailing and trapping efficiency
      were evaluated. The key factors included the ion strength of the mobile phase, a
      loading flow rate of the sample onto the trap column, and selection of a proper
      stationary phase of the trap column for a given set of analytes. These parameters
      have proven to be essential for minimizing any unwanted chromatographic peak
      tailing. The bulk derivatization of the analytes in the biological fluids and its
      relationship to the observed matrix effects was evaluated as well. 

PMID- 24913366
TI  - Portable, fully autonomous, ion chromatography system for on-site analyses.
AB  - The basic operating principles of a portable, fully autonomous, ion
      chromatography system are described. The system affords the user the ability to
      collect and analyze samples continuously for 27 days, or about 1930 injections
      before needing any user intervention. Within the 13 kg system, is a fully
      computer controlled autosampling, chromatography and data acquisition system. An
      eluent reflux device (ERD), which integrates eluent suppression and generation in
      a single multi-chambered device, is used to minimize eluent consumption. During
      operation, about 1 MUL of water per minute is lost to waste while operating
      standard-bore chromatography at 0.5 mL min(-1) due to eluent refluxing. Over the
      course of 27 days, about 100mL of rinse water is consumed, effectively
      eliminating waste production. Data showing the reproducibility (below 1% relative
      standard deviation over 14 days) of the device is also presented. Chromatographic
      analyses of common anions (Cl(-), NO3(-), SO4(2-), PO4(3-)), is accomplished in
      under 15 min using a low backpressure guard column with ~ 25 mM KOH isocratic
      elution. For detection, a small capacitively-coupled contactless conductivity
      detector (C4D) is employed, able to report analytes in the sub to low micromolar
      range. Preconcentration of the injected samples gives a 50-fold decrease in
      detection limits, primarily utilized for in-situ detection of phosphate (LOQ 10
      MUg L(-1)). Field analyses are shown for multiple on-site analyses of stream
      water indifferent weather conditions.

PMID- 24913367
TI  - Chiral ionic liquids in chromatographic and electrophoretic separations.
AB  - This report provides an overview of the application of chiral ionic liquids
      (CILs) in separation technology, and particularly in capillary electrophoresis
      and both gas and liquid chromatography. There is a large number of CILs that have
      been synthesized and designed as chiral agents. However, only a few have
      successfully been applied in separation technology. Even though this application
      of CILs is still in its early stages, the scientific interest is increasing
      dramatically. This article is focused on the use of CILs as chiral selectors,
      background electrolyte additives, chiral ligands and chiral stationary phases in
      electrophoretic and chromatographic techniques. Different examples of CILs, which
      contain either a chiral cation, a chiral anion or both, are presented in this
      review article, and their major advantages along with their potential
      applications in chiral electrophoretic and chromatographic recognition are
      discussed. 

PMID- 24913368
TI  - A practical application of wavelet moment method on the quantitative analysis of
      Shuanghuanglian oral liquid based on three-dimensional fingerprint spectra.
AB  - The overlapping and shifts of peaks and noise signals appear mostly in high
      performance liquid chromatography (HPLC) experiments. A practical application of
      wavelet moment method on the quantitative analysis of the main active components
      in Shuanghuanglian oral liquid samples was presented based on the determination
      of HPLC coupled with photodiode array detector (PAD). The wavelet moments were
      calculated from the divided regions in the grayscale images of three-dimensional
      (3D) HPLC-PAD fingerprint spectra according to the target peak(s), and then used
      to establish linear models, respectively. The correlation coefficients (R) were
      more than 0.9980 within the test ranges. The intra- and inter-day variations were
      less than 1.13% and 1.10%, respectively. The recovery ranged from 96.2% to
      102.7%. The overall LODs and LOQs were less than 0.2 MUg/mL and 0.7 MUg/mL,
      respectively. Our study indicated that wavelet moment approach could defuse the
      overlapping and shifts of peaks and noise signals in the chromatographic
      determination owing to its multi-resolution and inherently invariance properties.
      Thus the analytical time was shortened, and the obtained results were reliable
      and accurate.

PMID- 24913369
TI  - Recent applications of carbon nanotube sorbents in analytical chemistry.
AB  - Carbon nanotubes (CNTs) are still awakening scientists' interest because of their
      inherent properties as well as their applications in a wide variety of fields.
      Regarding Analytical Chemistry, and although they have also been used as
      stationary phases in chromatography or pseudostationary phases in capillary
      electrophoresis, they have also found a particular place in sorbent-based
      extraction techniques. In fact, they are currently used as sorbents in solid
      phase extraction, solid-phase microextraction, stir-bar sorptive extraction and
      matrix solid-phase dispersion, for analyte enrichment or storage, sample
      fractionation or clean-up as well as support for derivatization reactions. CNT
      surface is tuneable and, as a result, they can be suitably functionalized,
      aggregated or linked to other supports which increase their potential use as
      sorbents. They can also be arranged under different formats (cartridges, fibers,
      stir bars, disks, etc.) or even combined with magnetic nanoparticles, which
      clearly enlarge their applications. This review article overviews the most recent
      applications of CNTs as sorbent materials, covering the period from 2010 to early
      2014. 

PMID- 24913362
TI  - Genetic and molecular bases of yield-associated traits: a translational biology
      approach between rice and wheat.
AB  - Transferring the knowledge bases between related species may assist in enlarging
      the yield potential of crop plants. Being cereals, rice and wheat share a high
      level of gene conservation; however, they differ at metabolic levels as a part of
      the environmental adaptation resulting in different yield capacities. This review
      focuses on the current understanding of genetic and molecular regulation of yield
      associated traits in both crop species, highlights the similarities and
      differences and presents the putative knowledge gaps. We focus on the traits
      associated with phenology, photosynthesis, and assimilate partitioning and
      lodging resistance; the most important drivers of yield potential. Currently,
      there are large knowledge gaps in the genetic and molecular control of such major
      biological processes that can be filled in a translational biology approach in
      transferring genomics and genetics informations between rice and wheat.

PMID- 24913370
TI  - Capillary electrophoresis-based immobilized enzyme reactor using particle-packing
      technique.
AB  - A novel method using particle-packing technique to fabricate capillary
      electrophoresis (CE)-based immobilized enzyme reactor (IMER) was accomplished by
      utilizing perfusive silica single particles as the frits and large-pore beads as
      the enzyme supports. The fabrication procedure is rapid and simple; the length
      and enzyme loading amount of the CE-IMERs could be easily adjusted. Performance
      and feasibility of the CE-IMERs were investigated using on-line trypsin digestion
      as the model enzyme reaction. High reproducible on-line enzyme assay was
      demonstrated with RSD less than 4.1% and 3.8% for peak area and migration time of
      the substrate and product over 100 consecutive runs, respectively. The enzyme can
      still maintain the activity for at least 10 days, indicating remarkably stability
      of the CE-IMERs. The CE-IMERs were successfully applied for accurate analysis of
      trypsin inhibition as well as on-line digestion of standard proteins (myoglobin
      and BSA). The present method provides a new interesting alternative to open
      tubular and monolithic CE-IMERs, thus expands the application of the CE technique
      for on-line enzyme assay and analysis and characterization of peptides and
      proteins.

PMID- 24913372
TI  - Targeted therapies: TH3RESA trial, overcoming hurdles in breast cancer.

PMID- 24913373
TI  - Breast cancer: RARRES3-suppressing metastases to the lung in breast cancer.

PMID- 24913375
TI  - Risk perception is not associated with attendance at a preventive intervention
      for type 2 diabetes mellitus among South Asians at risk of diabetes.
AB  - OBJECTIVE: To evaluate the association between risk perception and attendance in
      a diabetes prevention programme among South Asians with a high risk for diabetes.
      DESIGN: An observational study. We measured risk perception during the baseline
      interview with causal beliefs, perceived susceptibility and perceived
      controllability. We used logistic regression to examine the relationship between
      risk perception and attendance. We adjusted for relevant sociodemographic
      factors, screening results and psychosocial factors. SETTING: The Hague, the
      Netherlands. SUBJECTS: Five hundred and thirty-five Hindustani Surinamese (South
      Asians) aged 18-60 years from a lifestyle-versus-control intervention for the
      prevention of diabetes. RESULTS: In total, 68.2% attended the lifestyle or
      control intervention. Participants perceived lifestyle and heredity to increase
      the risk of diabetes and perceived increasing physical activity to decrease it.
      Only 44.2% of the participants perceived themselves as susceptible to diabetes
      and only those who perceived a family history of diabetes as a cause of diabetes
      appeared to be more inclined to attend. However, after adjustment for
      confounding, the association was not statistically significant. CONCLUSIONS: Risk
      perception was not significantly associated with attendance. The results suggest
      that increasing the risk perception alone in this South Asian population is
      unlikely to increase the attendance at a diabetes prevention programme.

PMID- 24913376
TI  - Novel developments in Crohn's disease.

PMID- 24913374
TI  - Metronomics: towards personalized chemotherapy?
AB  - Since its inception in 2000, metronomic chemotherapy has undergone major advances
      as an antiangiogenic therapy. The discovery of the pro-immune properties of
      chemotherapy and its direct effects on cancer cells has established the intrinsic
      multitargeted nature of this therapeutic approach. The past 10 years have seen a
      marked rise in clinical trials of metronomic chemotherapy, and it is increasingly
      combined in the clinic with conventional treatments, such as maximum-tolerated
      dose chemotherapy and radiotherapy, as well as with novel therapeutic strategies,
      such as drug repositioning, targeted agents and immunotherapy. We review the
      latest advances in understanding the complex mechanisms of action of metronomic
      chemotherapy, and the recently identified factors associated with disease
      resistance. We comprehensively discuss the latest clinical data obtained from
      studies performed in both adult and paediatric populations, and highlight ongoing
      clinical trials. In this Review, we foresee the future developments of metronomic
      chemotherapy and specifically its potential role in the era of personalized
      medicine. 

PMID- 24913377
TI  - Epidemiology of inflammatory bowel disease: focus on Asia.
AB  - The epidemiology of inflammatory bowel disease (IBD) is changing globally.
      Incidence and prevalence may have stabilized in high-incidence areas such as
      North America and Europe but they continue to rise in previously low-incidence
      areas such as Eastern Europe, Asia, and much of the developing world. This
      epidemiological shift likely relates to westernization of lifestyle, changes in
      diet, and improved hygiene as part of socioeconomic development in developing
      countries. In Asia, UC is more prevalent than CD, although the UC:CD ratio is
      narrowing in certain areas. Clinical manifestations of IBD in Asia resemble the
      Western population, but with some differences, including higher prevalence of
      males and ileo-colonic CD, less familial clustering, lower surgical rates and
      extra-intestinal manifestations. These differences may relate to time, genetics
      and environmental factors. Studying the epidemiology of IBD in an area of rapidly
      increasing incidence may lead to discovery of important etiologic factors
      associated with disease development. 

PMID- 24913379
TI  - How will insights from genetics translate to clinical practice in inflammatory
      bowel disease?
AB  - Inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis,
      is a chronic inflammatory disease of the gut, which arises through an excessive
      immune response to the normal gut flora in a genetically susceptible host. The
      disease affects predominantly young adults and due to its chronic and relapsing
      nature gives rise to a high disease burden both financially, physically and
      psychologically. Current therapy still cannot prevent the need for surgical
      intervention in more than half of IBD patients. Consequently, advances in IBD
      therapy are of high importance. Recently, several new forms of targeted therapy
      have been introduced, which should improve surgery-free prognosis of IBD
      patients. Recent identification of genetic risk variants for IBD has led to new
      insights into the biological mechanisms of the disease, which will, in the
      future, lead to new targeted therapy. In the meantime repositioning of drugs from
      biologically similar diseases towards IBD might lead to new IBD therapies. 

PMID- 24913378
TI  - Genetic studies of Crohn's disease: past, present and future.
AB  - The exact aetiology of Crohn's disease is unknown, though it is clear from early
      epidemiological studies that a combination of genetic and environmental risk
      factors contributes to an individual's disease susceptibility. Here, we review
      the history of gene-mapping studies of Crohn's disease, from the linkage-based
      studies that first implicated the NOD2 locus, through to modern-day genome-wide
      association studies that have discovered over 140 loci associated with Crohn's
      disease and yielded novel insights into the biological pathways underlying
      pathogenesis. We describe on-going and future gene-mapping studies that utilise
      next generation sequencing technology to pinpoint causal variants and identify
      rare genetic variation underlying Crohn's disease risk. We comment on the utility
      of genetic markers for predicting an individual's disease risk and discuss their
      potential for identifying novel drug targets and influencing disease management.
      Finally, we describe how these studies have shaped and continue to shape our
      understanding of the genetic architecture of Crohn's disease. 

PMID- 24913380
TI  - Exploring & exploiting our 'other self' - does the microbiota hold the key to the
      future therapy in Crohn's?
AB  - Inflammatory bowel diseases (IBD) with its two major forms Crohn's disease (CD)
      and ulcerative colitis (UC) are chronic relapsing disorders leading to
      inflammation of the gastrointestinal tract. Although the precise aetiology of IBD
      remains unclear, several factors are believed to contribute to disease
      pathogenesis. Among these, the role of the intestinal microbiota has become more
      and more appreciated. Evidence from experimental and clinical studies strongly
      suggests that chronic intestinal inflammation results from a dysregulated immune
      response towards components of the microbiota in genetically susceptible hosts.
      The growing perception of the microbiota as a major driver of disease
      pathogenesis raises the question, if the intestinal microbiota can be used as a
      therapeutic target in CD. Based on what we know about host microbiota
      interactions in health and disease, the objective of this review is to address
      the question if the microbiota holds the key to the future therapy in CD. 

PMID- 24913381
TI  - Insights from immunology: new targets for new drugs?
AB  - Rapid advances in our understanding of inflammatory bowel diseases have resulted
      from the synthesis of data from experimental and genetic studies. These have
      suggested a wide range of potential immunological targets with both local and
      systemic scope. Drugs to several of these targets have now reached phase I/II
      studies, and are discussed in the context of their scientific rationale. However,
      despite the advent of new classes of therapeutics targeting cellular trafficking
      and intracellular mediators of cytokine signalling, the armamentarium of
      effective therapeutics remains sparse. Only with more detailed experimental
      medicine studies will this imbalance be resolved. 

PMID- 24913382
TI  - Diagnostic imaging in Crohn's disease: what is the new gold standard?
AB  - Historically Barium and isotope studies been used for imaging of inflammatory
      bowel disease (IBD) but carry risk of radiation exposure. Use of Barium is
      declining resulting in fewer radiologists that have the necessary expertise.
      Isotopes studies lack anatomical definition but 18F - fludeoxyglucose (FDG)
      positron emission tomography (PET) shows promise in accurate assessment of
      disease compared to endoscopy. Computerised tomography (CT) is particularly
      useful in assessment of complications of Crohn's disease (CD) but radiation
      exposure is high. CT enterography (CTE) has improved visualisation of small bowel
      mucosal disease and allows assessment of disease activity. Ultrasound is
      increasingly used for preliminary assessment of patients with potential IBD.
      Although widely available and economically attractive, the expertise required is
      not widespread. Finally magnetic resonance imaging (MRI) is proving to be the
      most accurate tool for assessment of disease extent and distribution. MRI of the
      pelvis has superseded other techniques in assessment of peri-anal fistulation. 

PMID- 24913383
TI  - Not all monoclonals are created equal - lessons from failed drug trials in
      Crohn's disease.
AB  - The recent success of the anti-integrin antibody Vedolizumab can barely conceal
      the fact that the biologics armamentarium in Crohn's disease has barely evolved
      beyond TNF blockers so far. This contrasts with other immune-related diseases
      considered mechanistically and genetically closely related, such as psoriasis and
      rheumatoid arthritis, where approved biologics target a variety of independent
      biological mechanisms. Several pharmacological assets that entered clinical
      development have proven ineffective, or less effective than originally
      anticipated. While blockade of IL-17A and its receptor via Secukinumab and
      Brodalumab, respectively, worsened Crohn's disease, the beneficial effect of IL
      12/23 p40 blockade via Ustekinumab appeared confined to a subpopulation of
      Crohn's disease patients who have previously failed on TNF blockers. Clinical
      development of the IFNgamma blocker Fontolizumab was stopped despite
      demonstrating some clinical benefit, while the T cell co-stimulation blocker
      Abatacept did not exhibit any hint towards efficacy in Crohn's disease. Here I
      review results from these individual development programmes, and also reflect on
      the lack of efficacy of the TNF blocker Etanercept. I will discuss aspects of
      individual trials that might have confounded their interpretation and highlight
      the evolution in primary and secondary endpoints that have contributed to
      increasing robustness of results obtained in recent years. Finally, I suggest
      that mechanistic studies in murine genetic models combined with exploratory
      immunological studies incorporated in early drug development may represent the
      key for identifying the next generation of successful pharmacological targets in
      Crohn's disease. 

PMID- 24913384
TI  - Can we get more from our current treatments?
AB  - Crohn's disease is a chronic incurable condition that normally requires lifelong
      treatment. Whilst the anti-TNF agents have revolutionised the management of
      Crohn's disease over the last fifteen years, they are not a panacea. In
      particular, in part due to their immunogenic nature, loss of response limits
      their long term effectiveness in many patients. The only other long term disease
      modifying options are the immunomodulators, methotrexate, azathioprine and
      mercaptopurine. Therefore, given the limited number of drugs available to treat
      Crohn's disease, it is important that efforts are made to ensure that drugs are
      used in the best way possible as once a drug is deemed ineffective, it is rarely
      used again. For the growing number of patients who have active disease despite
      having been exposed to all standard therapies, failure to optimise drug therapy
      may lead to missed opportunities in the management of their disease. In this
      review, optimisation of drugs commonly used in the management of Crohn's disease
      will be discussed. 

PMID- 24913385
TI  - The biosimilar road in inflammatory bowel disease: the right way?
AB  - The biologicals have led to dramatic changes in the management of immune-mediated
      diseases, and the subsequent development of their biosimilars may reduce the high
      costs of these agents. However, there remain concerns about the true equivalence
      of a biosimilar and its reference product, as well as around immunogenicity of
      these agents in IBD, although studies on rheumatoid arthritis support the
      similarity of biosimilars and their originators. Many of the biologicals are
      approved for multiple indications, but it is not always possible to extrapolate
      across indications for the corresponding biosimilars. For both reference agents
      and biosimilars, rare adverse events and long-term efficacy and safety can only
      be assessed through post marketing surveillance; therefore, particular emphasis
      should be placed on the traceability of these agents in clinical practice.
      Lastly, based on current data, biosimilars cannot be considered simple
      substitutes of reference products in IBD, unless demonstrated by well-designed
      randomized controlled trials. 

PMID- 24913386
TI  - Treatment algorithms in Crohn's - up, down or something else?
AB  - Crohn's disease is a chronic, progressive and disabling condition. New
      therapeutic goals have emerged in Crohn's disease such as the need to look beyond
      symptoms by achieving mucosal healing that is known to be associated with better
      outcomes. Anti-TNF (Tumour Necrosis Factor) therapy is the most potent drug class
      to induce and maintain mucosal healing in Crohn's disease. Recent evidence
      indicates that the efficacy profile of thiopurines has been overestimated while
      the increased risk of malignancies (lymphoma, non-melanoma skin cancers, myeloid
      disorders) has been underestimated. Methotrexate is well-tolerated, but its
      potential for disease modification is unknown. Achieving mucosal healing in
      patients with early Crohn's disease might be the best way to change disease
      course and patients' life. In 2014, anti-TNF treatment should be the first-line
      therapy in patients with Crohn's disease who suffer from severe and/or
      complicated disease and in those with poor prognostic factors. In the remaining
      patients, a rapid step-up approach based on a tight monitoring is recommended. 

PMID- 24913387
TI  - Immunisations in Crohn's disease: who? why? what? when?
AB  - Immunosuppression induced by drugs increase the risk of infections in Crohn's
      disease (CD) patients. The vaccination rate in CD patients is usually low due to
      inaccurate information concerning the safety and efficacy of vaccines. Vaccines
      and immunoglobulins, are artificial ways of protection from common infectious
      diseases and they have had a major effect on mortality. Herein we detail the need
      of protection induced by vaccines of measles, varicella, Zoster, papillomavirus,
      shingles, pneumococcal invasive disease, influenza, hepatitis A and B in CD at
      diagnosis and during the course of the disease even during immunosuppression
      periods but with different singularities. Vaccination in CD travellers and the
      matters related to immunization of household healthy members of immunosuppressed
      patients are also discussed. 

PMID- 24913388
TI  - The surgical intervention: earlier or never?
AB  - Crohn's disease (CD) is a chronic and progressive disease characterized by the
      presence of inflammation in different segments of the digestive tract, resulting
      in damages of the entire wall. Untreated or treated inappropriately, this
      eventually might result in stricturing and/or penetrating complications.
      Traditionally, the first line of treatment is medical, and surgery reserved for
      those who failed medical therapy. Considerable progresses have been made in the
      surgical therapy of CD over the past two decades. Some surgical interventions
      such as those consisting in the resection of long segments or leading to a
      definitive stoma should be avoided and performed only in case of treatment
      failure. On the other side, well-indicated and minimal invasive surgery can be
      considered as an alternative to long-term medical therapy for certain
      indications. The decision of performing early surgery should take in account the
      strategy that will be applied post-operatively. Decision making in
      multidisciplinary teams is paramount. 

PMID- 24913389
TI  - Improving the outcome of fistulising Crohn's disease.
AB  - Fistulas are a frequent manifestation of Crohn's disease (CD) and can result in
      considerable morbidity. Approximately 35% of all patients with CD will experience
      one fistula episode during their disease course of which 54% is perianal. The
      major symptoms of patients with perianal fistulas are constant anal pain, the
      formation of painful swellings around the anus and continuous discharge of pus
      and/or blood from the external fistula opening. The exact aetiology of perianal
      fistulas in CD patients remains unclear, but it is thought that a penetrating
      ulcer in the rectal mucosa caused by active CD forms an abnormal passage between
      the epithelial lining of the rectum and the perianal skin. Genetic,
      microbiological and immunological factors seem to play important roles in this
      process. Although the incidence of perianal fistulas in patients with CD is quite
      high, an effective treatment is not yet discovered. In this review all available
      medical and surgical therapies are discussed and new treatment options and
      research targets will be highlighted. 

PMID- 24913390
TI  - When can we cure Crohn's?
AB  - Crohn's disease is a life-long idiopathic inflammatory disease which affects the
      entire gastrointestinal tract and occasionally extra-intestinal organs. CD is
      thought to result from complex interactions between environmental factors, the
      gut microbes, and the genetic background and the immune system of the host. In
      the last decades research on these pathogenetic components, and especially on
      mucosal immunity, has led to the development of biologic agents and therapeutic
      strategies that have improved dramatically the treatment of CD but we are still
      far away from curing the disease. If there is a treatment for CD that will
      probably evolve through methodical steps towards integrating research on all the
      components involved in the pathogenesis of CD. This holistic and global approach
      may aid at unravelling the mysteries of CD and developing novel agents and
      therapeutic strategies which by targeting multiple pathogenetic pathways and at
      different stages of disease may lead hopefully to cure. 

PMID- 24913391
TI  - Integrated diagnostic and therapeutic techniques: Toward an intelligent medical
      system.

PMID- 24913393
TI  - Time-evolution scenarios for short-range depletion gels subjected to the
      gravitational stress.
AB  - By exploiting photon correlation imaging and ghost particle velocimetry, two
      novel optical correlation techniques particularly suited to the investigation of
      the microscopic dynamics of spatially heterogeneous samples, we investigate the
      settling and restructuring dynamics of colloidal gels generated by short-ranged
      depletion interactions. Three distinct regions can be clearly set apart within
      the liquid-liquid coexistence region of the phase diagram where gel formation is
      observed. When depletion forces are barely sufficient to drive the system within
      the metastable region, an initial disordered gel hosts the rapid nucleation of
      crystallites, which stress the gel structure until it fully collapses, leading to
      the formation of a macroscopic colloidal crystal. For stronger attractive forces,
      two distinct scenarios are observed, depending on the particle volume fraction
      phi0 of the original suspension. At low phi0, the gel breaks after a short delay
      time into separate clusters, which rapidly settle until they compact in a denser
      disordered phase. The latter eventually undergoes a slow compression, which is
      accounted for by a poroelastic model where the microscopic gel dynamics is fully
      ruled by its macroscopic deformation. Yet, it is the intermediate stage between
      cluster settling and final compaction which displays very peculiar features,
      evidenced by anomalous settling profiles which are not shared, to our knowledge,
      by any other sedimentation processes investigated so far. For larger values of
      phi0, gel breaking is conversely suppressed, the structure undergoes a continuous
      compression that cannot be explained by a poroelastic model, and the microscopic
      dynamics is characterized by logarithmic correlation functions resembling those
      found for attractive glasses. 

PMID- 24913392
TI  - Unresolved mourning, supernatural beliefs and dissociation: a mediation analysis.
AB  - Unresolved mourning is marked by disorganized behavior and states of mind. In
      this study, we speculated that pathological dissociation would mediate the
      effects of unresolved mourning on supernatural beliefs. This hypothesis was
      determined based on findings that indicate an association between higher levels
      of dissociation, stronger beliefs in the supernatural and unresolved mourning. We
      examined two groups of participants, one classified as non-unresolved (non-U) (n
      = 56) and the other as unresolved (n = 26) (U) with respect to past loss/trauma
      as measured by the Adult Attachment Interview (AAI). Two self-report instruments
      were administered to measure supernatural beliefs and dissociation. As
      hypothesized, the multivariate analysis of variance indicated mean differences
      between the two groups. The unresolved group had greater belief in the
      supernatural and more pathological dissociative processes. The mediation analysis
      demonstrated that pathological dissociation fully mediated the effects of
      unresolved mourning on supernatural beliefs.

PMID- 24913394
TI  - Are platelet concentrates an ideal biomaterial for arthroscopic rotator cuff
      repair? A meta-analysis of randomized controlled trials.
AB  - PURPOSE: The present study aims to conduct a meta-analysis of Level I evidence
      studies to investigate the efficacy of concomitant platelet concentrate (PC) used
      in arthroscopic rotator cuff repair. METHODS: We systematically searched
      electronic databases to identify randomized controlled trials (RCTs) evaluating
      the role of PC augmentation in arthroscopic rotator cuff repairs for patients
      with full-thickness tears. The search strategy followed the requirements in the
      Cochrane Library Handbook. The primary outcome was retearing of the rotator cuff.
      Functional outcomes were analyzed in terms of Constant score, specific Constant
      pain score, University of California, Los Angeles (UCLA) shoulder score, Simple
      Shoulder Test (SST) score, and American Shoulder and Elbow Surgeons (ASES) score.
      RESULTS: Seven studies with a total of 417 patients available at the latest
      follow-up reporting data about retears were analyzed in this meta-analysis.
      However, 4 studies with Constant scores (n = 237), 3 studies with UCLA scores (n
      = 168), 2 studies with Constant pain scores (n = 164), 2 studies with ASES scores
      (n = 101), and 2 studies with SST scores (n = 121) were analyzed. The retear
      rates and functional scores showed that there was no significant efficacy of PC
      application in arthroscopic rotator cuff repairs. CONCLUSIONS: This meta-analysis
      of high-level evidence suggests that PCs have no benefit regarding retear rate
      and overall clinical outcomes for the arthroscopic repair of full-thickness
      rotator cuff tears. LEVEL OF EVIDENCE: Level II, meta-analysis of randomized
      controlled trials.

PMID- 24913395
TI  - Prevention of portal hypertension: from variceal development to clinical
      decompensation.
AB  - Pharmacological treatment of portal hypertension (PH) has been exclusively
      devoted to gastroesophageal varices-related events at different frameworks,
      including prophylactic, emergency, or preventive therapy. The goals of treatment
      are to avoid the first bleeding episode, stop active bleeding, and prevent
      bleeding recurrence, respectively. The objective of preprimary prophylaxis (PPP)
      is to avoid variceal development, and therefore it necessarily deals with
      patients with cirrhosis at earlier stages of the disease. At these earlier
      stages, nonselective beta-blockers (NSBBs) have been ineffective in preventing
      the development of varices and other complications of PH. Therefore, treatment
      should not rely on NSBB. It is possible that, at these earlier stages,
      etiological treatment of liver disease itself could prevent progression of PH.
      This review will focus mainly on early treatment of PH, because, if successful,
      it may translate into histological-hemodynamic improvements, avoiding not only
      variceal development, but also other PH-related complications, such as ascites
      and portosystemic encephalopathy. Moreover, the advent of new therapies may allow
      not only the prevention of the complications of PH, but also the chance of a
      substantial degree of regression in the cirrhotic process, with the possible
      prevention of hepatocellular carcinoma (HCC).

PMID- 24913397
TI  - Detection of trace ink compounds in erased handwritings using electrospray
      assisted laser desorption ionization mass spectrometry.
AB  - Writings made with erasable pens on paper surfaces can either be rubbed off with
      an eraser or rendered invisible by changing the temperature of the ink. However,
      trace ink compounds still remain in the paper fibers even after rubbing or
      rendering. The detection of these ink compounds from erased handwritings will be
      helpful in knowing the written history of the paper. In this study, electrospray
      assisted laser desorption ionization/mass spectrometry was used to characterize
      trace ink compounds remaining in visible and invisible ink lines. The ink
      compounds were desorbed from the paper surface by irradiating the handwritings
      with a pulsed laser beam; the desorbed analytes were subsequently ionized in an
      electrospray plume and detected by a quadrupole time-of-flight mass spectrometry
      mass analyzer. Because of the high spatial resolution of the laser beam,
      electrospray-assisted laser desorption ionization/mass spectrometry analysis
      resulted in minimal damage to the sample documents.

PMID- 24913396
TI  - Hydrogen/deuterium exchange in parallel with acid/base induced protein
      conformational change in electrospray droplets.
AB  - The exposure of electrospray droplets to vapors of deuterating reagents during
      droplet desolvation in the interface of a mass spectrometer results in
      hydrogen/deuterium exchange (HDX) on the sub-millisecond time scale. Deuterated
      water is used to label ubiquitin and cytochrome c with minimal effect on the
      observed charge state distribution (CSD), suggesting that the protein
      conformation is not being altered. However, the introduction of deuterated
      versions of various acids (e.g., CD3COOD and DCl) and bases (ND3) induces
      unfolding or refolding of the protein while also labeling these newly formed
      conformations. The extent of HDX within a protein CSD associated with a
      particular conformation is essentially constant, whereas the extent of HDX can
      differ significantly for CSDs associated with different conformations from the
      same protein. In some cases, multiple HDX distributions can be observed within a
      given charge state (as is demonstrated with cytochrome c) suggesting that the
      extent of HDX and CSDs share a degree of complementarity in their sensitivities
      for protein conformation. The CSD is established late in the evolution of ions in
      electrospray whereas the HDX process presumably takes place in the bulk of the
      droplet throughout the electrospray process. Back exchange is also performed in
      which proteins are prepared in deuterated solvents prior to ionization and
      exposed to undeuterated vapors to exchange deuteriums for hydrogens. The degree
      of deuterium uptake is easily controlled by varying the identity and partial
      pressure of the reagent introduced into the interface. Since the exchange occurs
      on the sub-millisecond time scale, the use of deuterated acids or bases allows
      for transient species to be generated and labeled for subsequent mass analysis.

PMID- 24913398
TI  - Explanation through density functional theory of the unanticipated loss of CO2
      and differences in mass fragmentation profiles of ritonavir and its rCYP3A4
      mediated metabolites.
AB  - In the present study, the metabolism of ritonavir was explored in the presence of
      rCYP3A4 using a well-established strategy involving liquid chromatography-mass
      spectrometry (LC-MS) tools. A total of six metabolites were formed, of which two
      were new, not reported earlier as CYP3A4-mediated metabolites. During LC-MS
      studies, ritonavir was found to fragment through six principal pathways, many of
      which involved neutral loss of CO2, as indicated through 44-Da difference between
      masses of the precursors and the product ions. This was unusual as the drug and
      the precursors were devoid of a terminal carboxylic acid group. Apart from the
      neutral loss of CO2, marked differences were also observed among the
      fragmentation pathways of the drug and its metabolites having intact N-methyl
      moiety as compared to those lacking N-methyl moiety. These unusual fragmentation
      behaviours were successfully explained through energy distribution profiles by
      application of the density functional theory.

PMID- 24913399
TI  - The role of physical and chemical properties of Pd nanostructured materials
      immobilized on inorganic carriers on ion formation in atmospheric pressure laser
      desorption/ionization mass spectrometry.
AB  - Fundamental parameters influencing the ion-producing efficiency of palladium
      nanostructures (nanoparticles [Pd-NP], nanoflowers, nanofilms) during laser
      irradiation were studied in this paper. The nanostructures were immobilized on
      the surface of different solid inorganic carrier materials (porous and mono
      crystalline silicon, anodic porous aluminum oxide, glass and polished steel) by
      using classical galvanic deposition, electroless local deposition and sputtering.
      It was the goal of this study to investigate the influence of both the
      nanoparticular layer as well as the carrier material on ion production for
      selected analyte molecules. Our experiments demonstrated that the dimensions of
      the synthesized nanostructures, the thickness of the active layers, surface
      disorders, thermal conductivity and physically or chemically adsorbed water
      influenced signal intensities of analyte ions during surface-assisted laser
      desorption/ionization (SALDI) while no effects such as plasmon resonance,
      photoelectric effect or catalytic activity were expected to occur. Excellent LDI
      abilities were seen for Pd-NPs immobilized on steel, while Pd nanoflowers on
      porous silicon exhibited several disadvantages; viz, strong memory effects,
      dependency of the analytical signal on amount of physically and chemically
      adsorbed water inside porous carrier, reduced SALDI activity from unstable
      connections between Pd and semiconductor material, decrease of the melting point
      of pure silicon after Pd immobilization and resulting strong laser ablation of
      metal/semiconductor complex, as well as significantly changed surface morphology
      after laser irradiation. The analytical performance of Pd-NP/steel was further
      improved by applying a hydrophobic coating to the steel surface before galvanic
      deposition. This procedure increased the distance between Pd-NPs, thus reducing
      thermal stress upon LDI; it simultaneously decreased spot sizes of deposited
      sample solutions.

PMID- 24913400
TI  - Gas-phase fluorine migration reactions in the radical cations of
      pentafluorosulfanylbenzene (Aryl-SF5) and benzenesulfonyl fluoride (Aryl-SO2F)
      derivatives and in the 2,5-xylylfluoroiodonium ion.
AB  - The gas-phase reactions of Aryl-SF5(.+) and Aryl-SO2F(.+) have been studied with
      the electron ionization tandem mass spectrometry. Such reactions involve F-atom
      migration from the S-atom to the aryl group affording the product ion Aryl-F(.+)
      by subsequent expulsion of SF4 or SO2, respectively. Especially, the 4
      pentafluorosulfanylphenyl cation 4-SF5C6H4(+) (m/z 203) from 4-NO2C6H4SF5(.+) by
      loss of .NO2 could occur multiple F-atom migration reactions to the product ion
      C6H4F3(+) (m/z 133) by loss of SF2 in the MS/MS process. The gas-phase reactions
      of 2,5-xylylfluoroiodonium (pXyl-I(+)F, m/z 251) have also been studied using the
      electrospray tandem mass spectrometry, which involve a similar F-atom migration
      process from the I-atom to the aryl group giving the radical cation of 2-fluoro-p
      xylene (or its isomer 4-fluoro-m-xylene, m/z 124) by reductive elimination of an
      iodine atom. All these gas-phase F-atom migration reactions from the heteroatom
      to the aryl group led to the aryl-F coupling product ions with a new formed
      C(Aryl)-F bond. Density functional theory calculations were performed to shed
      light on the mechanisms of these reactions.

PMID- 24913401
TI  - Evidence for ion-ion interactions between peptides and anions (HSO4- or ClO4-)
      derived from high-acidity acids.
AB  - The existence of gas-phase electrostatic ion-ion interactions between protonated
      sites on peptides ([Glu] Fibrinopeptide B, Angiotensin I and [Asn(1), Val(5)]
      Angiotensin II) and attaching anions (ClO4(-) and HSO4(-)) derived from strong
      inorganic acids has been confirmed by CID MS/MS. Evidence for ion-ion
      interactions comes especially from the product ions formed during the first
      dissociation step, where, in addition to the expected loss of the anion or
      neutral acid, other product ions are also observed that require covalent bond
      cleavage (i.e. H2O loss when several carboxylate groups are present, or NH3 loss
      when only one carboxylate group is present). For [[Glu] Fibrinopeptide B + HSO4](
      ), under CID, H2O water loss was found to require less energy than H2SO4
      departure. This indicates that the interaction between HSO4(-) and the peptide is
      stronger than the covalent bond holding the hydroxyl group, and must be an ion
      ion interaction. The strength and stability of this type of ion-pairing
      interaction are highly dependent on the accessibility of additional mobile
      charges to the site. Positive mobile charges such as protons from the peptide can
      be transferred to the attaching anion to possibly form a neutral that may depart
      from the complex. Alternatively, an ion-ion interaction can be disrupted by a
      competing proximal additional negatively charged site of the peptide that can
      potentially form a salt bridge with the positively charged site and thereby
      facilitate the attaching anion's departure.

PMID- 24913402
TI  - Comparison of the activation time effects and the internal energy distributions
      for the CID, PQD and HCD excitation modes.
AB  - Reproducibility among different types of excitation modes is a major bottleneck
      in the field of tandem mass spectrometry library development in metabolomics. In
      this study, we specifically evaluated the influence of collision voltage and
      activation time parameters on tandem mass spectrometry spectra for various
      excitation modes [collision-induced dissociation (CID), pulsed Q dissociation
      (PQD) and higher-energy collision dissociation (HCD)] of Orbitrap-based
      instruments. For this purpose, internal energy deposition was probed using an
      approach based on Rice-Rampserger-Kassel-Marcus modeling with three thermometer
      compounds of different degree of freedom (69, 228 and 420) and a thermal model.
      This model treats consecutively the activation and decomposition steps, and the
      survival precursor ion populations are characterized by truncated Maxwell
      Boltzmann internal energy distributions. This study demonstrates that the
      activation time has a significant impact on MS/MS spectra using the CID and PQD
      modes. The proposed model seems suitable to describe the multiple collision
      regime in the PQD and HCD modes. Linear relationships between mean internal
      energy and collision voltage are shown for the latter modes and the three
      thermometer molecules. These results suggest that a calibration based on the
      collision voltage should provide reproducible for PQD, HCD to be compared with
      CID in tandem in space instruments. However, an important signal loss is observed
      in PQD excitation mode whatever the mass of the studied compounds, which may
      affect not only parent ions but also fragment ions depending on the fragmentation
      parameters. A calibration approach for the CID mode based on the variation of
      activation time parameter is more appropriate than one based on collision
      voltage. In fact, the activation time parameter in CID induces a modification of
      the collisional regime and thus helps control the orientation of the
      fragmentation pathways (competitive or consecutive dissociations).

PMID- 24913403
TI  - Mass spectrometric behavior of anabolic androgenic steroids using gas
      chromatography coupled to atmospheric pressure chemical ionization source. Part
      I: ionization.
AB  - The detection of anabolic androgenic steroids (AAS) is one of the most important
      topics in doping control analysis. Gas chromatography coupled to (tandem) mass
      spectrometry (GC-MS(/MS)) with electron ionization and liquid chromatography
      coupled to tandem mass spectrometry have been traditionally applied for this
      purpose. However, both approaches still have important limitations, and,
      therefore, detection of all AAS is currently afforded by the combination of these
      strategies. Alternative ionization techniques can minimize these drawbacks and
      help in the implementation of a single method for the detection of AAS. In the
      present work, a new atmospheric pressure chemical ionization (APCI) source
      commercialized for gas chromatography coupled to a quadrupole time-of-flight
      analyzer has been tested to evaluate the ionization of 60 model AAS.
      Underivatized and trimethylsylil (TMS)-derivatized compounds have been
      investigated. The use of GC-APCI-MS allowed for the ionization of all AAS assayed
      irrespective of their structure. The presence of water in the source as modifier
      promoted the formation of protonated molecules ([M+H](+)), becoming the base peak
      of the spectrum for the majority of studied compounds. Under these conditions,
      [M+H](+), [M+H-H2O](+) and [M+H-2.H2O](+) for underivatized AAS and [M+H](+),
      [M+H-TMSOH](+) and [M+H-2.TMSOH](+) for TMS-derivatized AAS were observed as main
      ions in the spectra. The formed ions preserve the intact steroid skeleton, and,
      therefore, they might be used as specific precursors in MS/MS-based methods.
      Additionally, a relationship between the relative abundance of these ions and the
      AAS structure has been established. This relationship might be useful in the
      structural elucidation of unknown metabolites.

PMID- 24913404
TI  - Fundamental properties of a touchable high-power pulsed microplasma jet and its
      application as a desorption/ionization source for ambient mass spectrometry.
AB  - Plasma-based ambient desorption/ionization mass spectrometry (ADI-MS) has
      attracted considerable attention in many fields because of its capacity for
      direct sample analyses. In this study, a high-power pulsed microplasma jet
      (HPPMJ) was developed and investigated as a new plasma desorption/ionization
      source. In an HPPMJ, a microhollow cathode discharge is generated in a small hole
      (500 um in diameter) using a pulsed high-power supply. This system can realize a
      maximum power density of 5 * 10(8) W/cm(3). The measured electron number density,
      excitation temperature and afterglow gas temperature of the HPPMJ were 3.7 *
      10(15) cm(-3), 7000 K at maximum and less than 60  degrees C, respectively, which
      demonstrate that the HPPMJ is a high-energy, high-density plasma source that is
      comparable with an argon inductively coupled plasma while maintaining a low gas
      temperature. The HPPMJ causes no observable damage to the target because of its
      low gas temperature and electrode configuration; thus, we can apply it directly
      to human skin. To demonstrate the analytical capacity of ADI-MS using an HPPMJ,
      the plasma was applied to direct solid sample analysis of the active ingredients
      in pharmaceutical tablets. Caffeine, acetaminophen, ethenzamide,
      isopropylantipyrine and ibuprofen were successfully detected. Application to
      living tissue was also demonstrated, and isopropylantipyrine on a finger was
      successfully analyzed without damaging the skin. The limits of detection (LODs)
      for caffeine, isopropylantipyrine and ethenzamide were calculated, and LODs at
      the picogram level were achieved. These results indicate the applicability of the
      HPPMJ for high-sensitivity analysis of materials on a heat-sensitive surface.

PMID- 24913405
TI  - Hydrogen-deuterium exchange of alpha-carbon protons and fragmentation pathways in
      N-methylated glycine and alanine-containing peptides derivatized by quaternary
      ammonium salts.
AB  - Recently, we developed a selective and efficient method of hydrogen-deuterium
      exchange (HDX) at the alpha-carbon (alpha-C) of sarcosine residue (N
      methylglycine) in model peptides [Bachor et al. J. Mass Spectrom. 2014, 49, 43].
      Here, we report the influence of quaternary ammonium (QA) group on HDX at the
      alpha-C of sarcosine and N-methylalanine in peptides. The obtained results
      suggest a significant acceleration of the HDX in sarcosine residue caused by the
      presence of QA. The effect depends on the distance between the sarcosine residue
      and QA moiety. The deuterons, introduced at alpha-C, are resistant to the back
      exchange in acidic aqueous solution. The collision induced dissociation of the
      deuterium-labeled analogs of QA-tagged oligosarcosine peptides without mobile
      hydrogen revealed the mobilization of the hydrogens localized at alpha-C of
      sarcosine residue.

PMID- 24913406
TI  - Detection of oxygen addition peaks for terpendole E and related indole-diterpene
      alkaloids in a positive-mode ESI-MS.
AB  - This report describes that a regular positive electrospray ionization mass
      spectrometry (MS) analysis of terpendoles often causes unexpected oxygen
      additions to form [M + H + O](+) and [M + H + 2O](+), which might be a
      troublesome in the characterization of new natural analogues. The intensities of
      [M + H + O](+) and [M + H + 2O](+) among terpendoles were unpredictable and
      fluctuated largely. Simple electrochemical oxidation in electrospray ionization
      was insufficient to explain the phenomenon. So we studied factors to form [M + H
      + O](+) and [M + H + 2O](+) using terpendole E and natural terpendoles together
      with some model indole alkaloids. Similar oxygen addition was observed for
      1,2,3,4-tetrahydrocyclopent[b]indole, which is corresponding to the substructure
      of terpendole E. In tandem MS experiments, a major fragment ion at m/z 130 from
      protonated terpendole E was assigned to the substructure containing indole. When
      the [M + H + O](+) was selected as a precursor ion, the ion shifted to m/z 146.
      The same 16 Da shift of fragments was also observed for 1,2,3,4
      tetrahydrocyclopent[b]indole, indicating that the oxygen addition of terpendole E
      took place at the indole portion. However, the oxygen addition was absent for
      some terpendoles, even whose structure resembles terpendole E. The breakdown
      curves characterized the tandem MS features of terpendoles. Preferential
      dissociation into m/z 130 suggested the protonation tendency at the indole site.
      Terpendoles that are preferentially protonated at indole tend to form oxygen
      addition peaks, suggesting that the protonation feature contributes to the oxygen
      additions in some degrees.

PMID- 24913409
TI  - Low concordance and resistance mutation emergence in the HIV protease gene among
      circulating and cell-associated viruses at viral replication episodes during
      darunavir/ritonavir monotherapy.
AB  - OBJECTIVE: To assess the changes on the HIV protease gene in plasma and
      peripheral blood mononuclear cell (PBMC) compartments during viral replication
      episodes in patients on boosted-darunavir monotherapy (mtDRV/rtv). METHODS: A
      prospective study was carried out in which adult HIV-1-infected patients who
      started mtDRV/rtv after viral suppression for >= 6 months with no major darunavir
      related resistance mutations were enrolled. Patients with two consecutive plasma
      HIV RNA measurements >200 HIV-1 RNA copies/mL were considered as having
      virological failure (VF), while patients with two consecutive plasma HIV RNA
      measurements >50 copies/mL without meeting the VF criteria were considered to
      have virological rebound (VR). HIV protease genotypic profiles from plasma and
      PBMCs were performed at baseline and at VF and VR episodes. RESULTS: One hundred
      and fifty patients were included in the study, with overall VF and VR rates of
      14% (n=21) and 14.7% (n=22), respectively. No major darunavir resistance
      mutations were observed in the plasma or PBMC samples. Circulating and cell
      associated viruses showed a wild-type protease gene sequence in 54% and 23% of
      patients, respectively while the remainder patients only harboured minor protease
      inhibitor-associated mutations. Full concordance between plasma RNA and PBMC DNA
      protease genotypes was found in 23% of the sequences. CONCLUSIONS: No darunavir
      related mutations were found in patients with VF or VR, either in plasma or in
      PBMCs; thus, simplification to mtDRV/rtv does not comprise future antiretroviral
      treatment options.

PMID- 24913410
TI  - Thyroid fine-needle aspiration cytology: performance data of neoplastic and
      malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment
      program thyroid fine-needle performance data.
AB  - BACKGROUND: Fine-needle aspiration of the thyroid is a common procedure, with an
      established role in reducing unnecessary thyroid surgery and identifying
      neoplasms and malignancies. METHODS: The study evaluated 1558 responses in the
      American Society for Clinical Pathology (ASCP) Non-GYN Assessment program of
      aspirates of thyroid neoplasms and malignancies and placed them into the
      following groups: group A (target or correct interpretation), group B (incorrect
      interpretation as a benign thyroid nodule), group C (incorrect interpretation
      malignant aspirate as thyroid neoplasm), and group D (malignant diagnosis with
      incorrect interpretation). In clinical practice, responses in groups A, C, and D
      would lead to surgical excision, whereas responses in group B would not. RESULTS:
      Of a total of 1558 responses, 78.5% of the responses were in group A, 8.5% in
      group B, 3.75% in group C, and 9.25% in group D. By individual diagnosis, the
      group rates were 86.5%, 0%, 11%, and 2.5% for anaplastic thyroid carcinoma; 83%,
      5.5%, 4.25%, and 7.25% for papillary thyroid carcinoma; 79%, 7%, 6%, and 8% for
      medullary thyroid carcinoma; 83.5% 6.75%, 0%, and 9.75% for Hurthle cell
      neoplasm; and 61%, 22%, 0%, and 17% for follicular neoplasm in groups A, B, C,
      and D respectively. CONCLUSIONS: Fine-needle aspiration was effective in
      diagnosing thyroid neoplasms and malignancies and in separating thyroid nodules
      into surgical and nonsurgical categories. Data from a large group of cytology
      professionals showed good performance; however, there is room for improvement,
      especially in making specific diagnoses. In particular, follicular neoplasm and
      follicular variant of papillary thyroid carcinoma were challenging diagnoses for
      participants.

PMID- 24913411
TI  - Elements and modulation of functional dynamics.
AB  - The existing structure-function paradigm of drug discovery has been evolving
      toward the essential incorporation of dynamics data. This new functional dynamics
      paradigm emphasizes conformational entropy as a driving force of protein function
      and intermolecular recognition. Conformational dynamics (a proxy of
      conformational entropy) impacts the degree of protein (dis)order and the
      constitution of the conformational ensemble, the mechanisms of allostery and drug
      resistance, and the free energy of ligand binding. Specific protein and ligand
      conformations facilitate favorable, reciprocal interactions. The number of
      protein and ligand conformers that exhibit favorable binding interactions will
      vary from system to system. All binding scenarios can modulate protein dynamics
      by various levels of enthalpic and entropic contribution, with significant
      influence on the functional dynamics of the system. Analysis and consideration of
      resulting changes of activity, signaling, catalysis, and subsequent phenotypic
      outcome are powerful motivations in the drug design process. 

PMID- 24913412
TI  - Effect of prior experience and task stability on the intrinsic muscle activity of
      the thumb.
AB  - Manual techniques involving the use of the thumb are commonly employed by
      physical therapists for treating patients with vertebral disorders. The demands
      on the intrinsic muscles of the thumb in these manual tasks are very different
      from those of the pinch tasks. The aim of this study was to investigate the
      influence of clinical experience and different mobilization techniques on the
      electromyographic activity (EMG) of thumb intrinsic muscles. Fifteen participants
      without exposure to manual techniques (the Novice Group) and fifteen physical
      therapists with at least 3 years of orthopaedic experience (the Experienced
      Group) participated. Each participant exerted thumb tip forces with 3 different
      posterioanterior (PA) glide techniques including unsupported, with digital
      support and with thumb interphalangeal joint supported by the index finger. The
      exerted force was increased from 25% to 100% maximum force at 25% increments on a
      6 component load cell. The thumb tip force and EMG activity of four intrinsic
      muscles (flexor pollicis brevis, adductor pollicis, abductor pollicis brevis,
      first dorsal interosseus) were recorded with surface electrodes. Both experience
      and technique influenced intrinsic muscle activity of the thumb. While
      participants of both groups generated the same magnitude of force, experienced
      participants generated less intrinsic muscle activity while performing PA glide
      through practice. However, novice participants increased activity of the
      intrinsic muscles in accordance with the stability status of the technique. PA
      glide with thumb interphalangeal joint supported by the index finger was a more
      stable technique as evidenced by smallest relative errors of thumb tip force. 

PMID- 24913413
TI  - Biomechanical analysis of two-step traction therapy in the lumbar spine.
AB  - Traction therapy is one of the most common conservative treatments for low back
      pain. However, the effects of traction therapy on lumbar spine biomechanics are
      not well known. We investigated biomechanical effects of two-step traction
      therapy, which consists of global axial traction and local decompression, on the
      lumbar spine using a validated three-dimensional finite element model of the
      lumbar spine. One-third of body weight was applied on the center of the L1
      vertebra toward the superior direction for the first axial traction. Anterior
      translation of the L4 vertebra was considered as the second local decompression.
      The lordosis angle between the superior planes of the L1 vertebra and sacrum was
      44.6 degrees  at baseline, 35.2 degrees  with global axial traction, and 46.4
      degrees  with local decompression. The fibers of annulus fibrosus in the
      posterior region, and intertransverse and posterior longitudinal ligaments
      experienced stress primarily during global axial traction, these stresses
      decreased during local decompression. A combination of global axial traction and
      local decompression would be helpful for reducing tensile stress on the fibers of
      the annulus fibrosus and ligaments, and intradiscal pressure in traction therapy.
      This study could be used to develop a safer and more effective type of traction
      therapy. 

PMID- 24913414
TI  - Utility of hand-held echocardiography in outpatient pediatric cardiology
      management.
AB  - Adult patient series have shown hand-held echocardiography (echo) units (HHE) to
      be accurate for rapid diagnosis and triage. This is the first study to evaluate
      the ability of HHE to inform decision making in outpatient pediatric cardiology.
      New pediatric cardiology patients in outpatient clinics staffed by six pediatric
      cardiologists (experience 1-17 years) were prospectively enrolled if an
      echocardiogram (echo) was ordered during their initial visit. After history and
      physical examination and before a standard echo, the cardiologists performed a
      bedside HHE examination (GE Vscan 1.7-3.8 MHz), documented findings, and made a
      clinical decision. Diagnoses and decisions based on HHE were compared with final
      management after the standard echo. The study enrolled 101 subjects (ages 9 days
      to 19 years). The cardiologists considered HHE imaging adequate for decision
      making for 80 of the 101 subjects. For 77 of the 80 subjects with acceptable HHE
      imaging (68/68 normal and 9/12 abnormal standard echoes), the HHE-based primary
      diagnoses and decisions agreed with the final management. The sensitivity of HHE
      was 75 % (95 % confidence interval [CI] 43-94 %) and the positive predictive
      value 100 % (95 % CI 66-100 %) for pediatric heart disease. The agreement between
      standard echocardiography and HHE imaging was substantial (kappa = 0.82).
      Excluding one of the least experienced cardiologists, HHE provided the basis for
      correct cardiac diagnoses and management for all the subjects with acceptable HHE
      imaging (58/58 normal and 9/9 abnormal echoes). In outpatient pediatric
      cardiology, HHE has potential as a tool to complement physical examination.
      Further investigation is needed to evaluate how value improves with clinical
      experience.

PMID- 24913415
TI  - Association between methionine synthase reductase A66G polymorphism and the risk
      of congenital heart defects: evidence from eight case-control studies.
AB  - Methionine synthase reductase (MTRR) plays a major role in hyperhomocysteinemia,
      a risk factor related to the occurrence of congenital heart defects (CHDs).
      However, the associations between MTRR polymorphism and CHDs have been
      inconclusive. Thus, a metaanalysis of eight case-control studies was conducted to
      investigate 3,592 cases and 3,638 control subjects for MTRR A66G polymorphism to
      identify the association. Odds ratios (ORs) and 95 % confidence intervals (95 %
      CIs) were used to assess the strength of the association. The results showed that
      MTRR A66G polymorphism was associated with a higher CHD risk in the allele
      comparison (G vs A: OR 1.163; 95 % CI 1.016-1.330; P heterogeneity = 0.004), the
      homozygote comparison (GG vs AA: OR 1.332; 95 % CI 1.020-1.740; P heterogeneity =
      0.035), and the dominant model (GG/AG vs AA: OR 1.218; 95 % CI 1.001-1.482; P
      heterogeneity = 0.001). In the subgroup analysis, this polymorphism was
      associated with CHDs in Asians in the homozygote comparison (GG vs AA: OR 1.427;
      95 % CI 1.017-2.001; P heterogeneity = 0.019) and the allele comparison (G vs A:
      OR 1.203; 95 % CI 1.018-1.422; P heterogeneity = 0.002). In summary, the
      metaanalysis demonstrated that MTRR A66G polymorphism is a risk factor for CHDs.
      Further studies should be performed to investigate the association of plasma
      homocysteine levels, enzyme activity, parental genotypes, and vitamin complex
      intakes with the risk of CHDs.

PMID- 24913417
TI  - Metformin in women with PCOS, pros.
AB  - Metformin is an old insulin sensitizer that has been widely used in women with
      polycystic ovary syndrome (PCOS) to treat metabolic comorbidities and may also
      improve ovarian dysfunction in women with PCOS. In fact, metformin may improve
      insulin resistance, a common finding of PCOS, and reduce insulin blood levels. In
      this way, androgen production rates can be reduced, and in a subset of women,
      menses abnormalities and ovulatory rates may improve. The current Endocrine
      Society Guidelines recommend the use of metformin during adolescence,
      particularly when excess body weight is present. In the presence of obesity and
      glucose intolerance states, particularly if those patients fail to modify their
      lifestyles, metformin may have some significant benefits. Finally, although this
      drug should not be used as a first-line treatment for ovulatory dysfunctions in
      adult women with PCOS, there are data supporting the suggestion that in many
      cases pretreatment with metformin may favor ovulatory response to clomiphene
      citrate. This article summarizes the available evidence in the favor of metformin
      use in women with PCOS and emphasizes the need for an individualized therapeutic
      approach. 

PMID- 24913418
TI  - Strict rules are needed for validation of G-protein-coupled receptor
      immunohistochemical studies in human tissues.

PMID- 24913419
TI  - Dosimetric comparison of volumetric modulated arc therapy and linear accelerator
      based radiosurgery for the treatment of one to four brain metastases.
AB  - INTRODUCTION: The purpose of this study is to compare and evaluate volumetric
      modulated arc therapy (VMAT) and linear accelerator-based radiosurgery (Linac RS)
      for the treatment of one to four brain metastases. METHODS: Radiotherapy plans
      for 10 patients with 1 to 4 brain metastases that were planned and treated using
      conventional Linac RS were replanned using a mono-isocentric VMAT technique using
      two to four arcs. The same doses, target volumes and organs at risk (OAR) were
      used in both plans. The plans were evaluated for target volume coverage, dose
      conformity, homogeneity and dose to OAR. RESULTS: For VMAT plans, 18/19 brain
      metastases met acceptable Radiation Therapy Oncology Group (RTOG) radiosurgery
      dose coverage, homogeneity and conformity criteria. There was no observed
      difference between the mean homogeneity indices for VMAT and Linac RS plans. VMAT
      plans had a lower mean RTOG conformity index compared with the Linac RS plans
      (1.10 +/- 0.06 versus 2.06 +/- 1.02). For the OAR, there was no difference in
      maximal doses to the brain stem, optic chiasm or optic nerves. The volume of
      normal brain receiving 12 Gy was lower in the VMAT plans (13.3 cm(3) versus 23.1
      cm(3) ) compared with the Linac RS plans. The mean total number of monitor units
      (MUs) was 31.3% less in the VMAT plans (5231.2 MU versus 3593.5 MU). CONCLUSIONS:
      Mono-isocentric VMAT plans using two to four arcs meet RTOG radiosurgery quality
      criteria in patients with one to four brain metastases, with an improvement in
      conformity and 12-Gy normal brain volume when compared with patients treated with
      Linac RS at our institution.

PMID- 24913421
TI  - In vivo assessment of new resorbable PEG-PPG-PEG copolymer/starch bone wax in
      bone healing and tissue reaction of bone defect in rabbit model.
AB  - In this study, in vivo performance of novel resorbable bone wax based on a
      miscible blend between PEG-PPG-PEG copolymer mixtures and pregelatinized starch
      at 0 and 25 percent by weight including hemostasis, tissue reaction and bone
      healing in a non-critical size tibia defect model were assessed and compared with
      commercial non-resorbable bone wax. Systemic reaction was evaluated by blood
      chemistry while local reaction, bone quantity and quality were evaluated by
      microcomputed tomography (microCT) and histology analyses. It was observed that
      the resorbable bone waxes did not show any adverse systemic reaction and resorbed
      from the defects within approximately 2 days after application. They were as
      effective as the commercial bone wax in hemostasis, but provided better adherence
      to the bone surface. The incorporation of pre-gelatinized starch in the
      formulation could further help in improved molding texture and decreased glove
      adherence. MicroCT and histology analyses showed that the resorbable bone waxes
      did not inhibit the osteogenesis whereas commercial bone wax impaired bone
      healing and displayed inflammation and foreign body reactions. 

PMID- 24913420
TI  - Fez family transcription factors: controlling neurogenesis and cell fate in the
      developing mammalian nervous system.
AB  - Fezf1 and Fezf2 are highly conserved transcription factors that were first
      identified by their specific expression in the anterior neuroepithelium of
      Xenopus and zebrafish embryos. These proteins share an N-terminal domain with
      homology to the canonical engrailed repressor motif and a C-terminal DNA binding
      domain containing six C2H2 zinc-finger repeats. Over a decade of study indicates
      that the Fez proteins play critical roles during nervous system development in
      species as diverse as fruit flies and mice. Herein we discuss recent progress in
      understanding the functions of Fezf1 and Fezf2 in neurogenesis and cell fate
      specification during mammalian nervous system development. Going forward we
      believe that efforts should focus on understanding how expression of these
      factors is precisely regulated, and on identifying target DNA sequences and
      interacting partners. Such knowledge may reveal the mechanisms by which Fezf1 and
      Fezf2 accomplish both independent and redundant functions across diverse tissue
      and cell types. 

PMID- 24913422
TI  - Effect of low-level laser therapy on repair of the bone compromised by
      radiotherapy.
AB  - Radiotherapy (RDT) is commonly used for cancer treatment, but high doses of
      ionizing radiation can directly affect healthy tissues. Positive biological
      effects of low-level laser therapy (LLLT) on bone repair have been demonstrated;
      however, this effect on surgical defects of bone previously compromised by
      radiotherapy has not been evaluated. The aim of this study was to investigate the
      influence of LLLT (lambda = 830 nm) in femur repair after ionizing radiation.
      Twenty Wistar rats were divided into four groups: control group (GC, n = 5)
      creation of bone defects (BDs) only; laser group (GL), with BD and LLLT (n = 5);
      radiotherapy group (GR), submitted to RDT and BD (n = 5); and radiotherapy and
      laser group (GRL), submitted to RDT, BD, and LLLT (n = 5). GL and GRL received
      punctual laser application (DE = 210 J/cm(2), P = 50 mW, t = 120 s, and beam
      diameter of 0.04 cm(2)) immediately after surgery, with 48-h interval during 7
      days. Animals were euthanized at 7 days after surgery, and bone sections were
      evaluated morphometrically with conventional microscopy. Bone repair was only
      observed in nonirradiated bone, with significant improvement in GL in comparison
      to GC. GR and GRL did not present any bone neoformation. The result demonstrated
      a positive local biostimulative effect of LLLT in normal bone. However, LLLT was
      not able to revert the bone metabolic damage due to ionizing radiation.

PMID- 24913423
TI  - Optical feedback-induced light modulation for fiber-based laser ablation.
AB  - Optical fibers have been used as a minimally invasive tool in various medical
      fields. However, due to excessive heat accumulation, the distal end of a fiber
      often suffers from severe melting or devitrification, leading to the eventual
      fiber failure during laser treatment. In order to minimize thermal damage at the
      fiber tip, an optical feedback sensor was developed and tested ex vivo. Porcine
      kidney tissue was used to evaluate the feasibility of optical feedback in terms
      of signal activation, ablation performance, and light transmission. Testing
      various signal thresholds demonstrated that 3 V was relatively appropriate to
      trigger the feedback sensor and to prevent the fiber deterioration during kidney
      tissue ablation. Based upon the development of temporal signal signatures, full
      contact mode rapidly activated the optical feedback sensor possibly due to heat
      accumulation. Modulated light delivery induced by optical feedback diminished
      ablation efficiency by 30% in comparison with no feedback case. However, long
      term transmission results validated that laser ablation assisted with optical
      feedback was able to almost consistently sustain light delivery to the tissue as
      well as ablation efficiency. Therefore, an optical feedback sensor can be a
      feasible tool to protect optical fiber tips by minimizing debris contamination
      and delaying thermal damage process and to ensure more efficient and safer laser
      induced tissue ablation.

PMID- 24913424
TI  - Temporal pulse shaping: a key parameter for the laser welding of dental alloys.
AB  - This study aims to describe the effect of pulse shaping on the prevention of
      internal defects during laser welding for two dental alloys mainly used in
      prosthetic dentistry. Single spot, weld beads, and welds with 80 % overlapping
      were performed on Co-Cr-Mo and Pd-Ag-Sn cast plates with a pulsed neodymium-doped
      yttrium aluminum garnet (Nd:YAG) laser. A specific welding procedure using
      adapted parameters to each alloy was completed. All the possibilities for pulse
      shaping were tested: (1) the square pulse shape as a default setting, (2) a
      rising edge slope for gradual heating, (3) a falling edge slope to slow the
      cooling process, and (4) a combination of rising and falling edges. The
      optimization of the pulse shape is supposed to produce defect-free welds (crack,
      pores, voids). Cross-section SEM observations and Vickers microhardness
      measurements were made. Pd-Ag-Sn was highly sensitive to hot cracking, and Co-Cr
      Mo was more sensitive to voids and small porosities (sometimes combined with
      cracks). Using a slow cooling ramp allowed a better control on the solidification
      process for those two alloys always preventing internal defects. A rapid slope
      should be preferred for Co-Cr-Mo alloys due to its low-laser beam reflectivity.
      On the opposite, for Pd-Ag-Sn alloy, a slow rising slope should be preferred
      because this alloy has a high-laser beam reflectivity. 

PMID- 24913425
TI  - Highlights and discoveries from the Chandra X-ray Observatory.
AB  - Within 40 years of the detection of the first extra-solar x-ray source in 1962,
      NASA's Chandra X-ray Observatory has achieved an increase in sensitivity of 10
      orders of magnitude, comparable to the gain in going from naked-eye observations
      to the most powerful optical telescopes over the past 400 years. Chandra is
      unique in its capabilities for producing sub-arcsecond x-ray images with 100-200
      eV energy resolution for energies in the range 0.08 < E < 10 keV, locating x-ray
      sources to high precision, detecting extremely faint sources, and obtaining high
      resolution spectra of selected cosmic phenomena. The extended Chandra mission
      provides a long observing baseline with stable and well-calibrated instruments,
      enabling temporal studies over timescales from milliseconds to years. In this
      report we present a selection of highlights that illustrate how observations
      using Chandra, sometimes alone, but often in conjunction with other telescopes,
      have deepened, and in some instances revolutionized, our understanding of topics
      as diverse as protoplanetary nebulae; massive stars; supernova explosions; pulsar
      wind nebulae; the superfluid interior of neutron stars; accretion flows around
      black holes; the growth of supermassive black holes and their role in the
      regulation of star formation and growth of galaxies; impacts of collisions,
      mergers, and feedback on growth and evolution of groups and clusters of galaxies;
      and properties of dark matter and dark energy.

PMID- 24913426
TI  - Development of a standardized training course for laparoscopic procedures using
      Delphi methodology.
AB  - BACKGROUND: Content, evaluation, and certification of laparoscopic skills and
      procedure training lack uniformity among different hospitals in The Netherlands.
      Within the process of developing a new regional laparoscopic training curriculum,
      a uniform and transferrable curriculum was constructed for a series of
      laparoscopic procedures. The aim of this study was to determine regional expert
      consensus regarding the key steps for laparoscopic appendectomy and
      cholecystectomy using Delphi methodology. METHODS: Lists of suggested key steps
      for laparoscopic appendectomy and cholecystectomy were created using surgical
      textbooks, available guidelines, and local practice. A total of 22 experts,
      working for teaching hospitals throughout the region, were asked to rate the
      suggested key steps for both procedures on a Likert scale from 1-5. Consensus was
      reached with Crohnbach's alpha >= 0.90. RESULTS: Of the 22 experts, 21 completed
      and returned the survey (95%). Data analysis already showed consensus after the
      first round of Delphi on the key steps for laparoscopic appendectomy (Crohnbach's
      alpha = 0.92) and laparoscopic cholecystectomy (Crohnbach's alpha = 0.90). After
      the second round, 15 proposed key steps for laparoscopic appendectomy and 30
      proposed key steps for laparoscopic cholecystectomy were rated as important (>=4
      by at least 80% of the expert panel). These key steps were used for the further
      development of the training curriculum. CONCLUSION: By using the Delphi
      methodology, regional consensus was reached on the key steps for laparoscopic
      appendectomy and cholecystectomy. These key steps are going to be used for
      standardized training and evaluation purposes in a new regional laparoscopic
      curriculum.

PMID- 24913427
TI  - Surgical complications in kidney transplantation: no evidence for a learning
      curve.
AB  - OBJECTIVE: To evaluate whether surgical complications after kidney
      transplantation correlate with surgeon's experience and whether individual
      surgeons' complication rates improve during their learning process. STUDY DESIGN:
      Retrospective analysis: A generalized linear mixed-effects model was used to
      identify risk factors for surgical complications. Plots of cumulative sums of
      complications were used to evaluate the individual surgeons' performance.
      SETTING: Single-center experience of a teaching hospital in Switzerland.
      PARTICIPANTS: Consecutive kidney transplant recipients operated from 1962 until
      2003. RESULTS: A total of 1496 kidney transplants were analyzed; 73% were from
      deceased donors and 27% from living donors. At least 1 surgical complication
      occurred in 352 patients (24%). Male gender (odds ratio [OR] = 1.35, 95% CI: 1.04
      1.74), donor's age (OR = 1.14, 95% CI: 1.06-1.24 per decade increment), and third
      or fourth vs. first or second transplant in a recipient (OR = 2.90, 95% CI: 1.02
      8.24) were significantly associated with surgical complications. The surgeon's
      transplant experience was not found to be associated with surgical complications.
      Even surgeons with an experience of less than 10 kidney transplants did not have
      higher complication rates, 30-day mortality, or 1-year graft survival. Individual
      surgeons' complication rates analyzed by cumulative sum plots did not improve
      with increasing experience. CONCLUSIONS: We present the largest single-center
      study on surgical complications after kidney transplantation, with unique data on
      the surgeon's experience for every single procedure. We found no evidence for a
      learning curve during training for kidney transplantation. We conclude that
      carefully selected experienced general and vascular surgeons can achieve good
      results in kidney transplantation after a relatively short training period.

PMID- 24913428
TI  - Scaling up short-term humanitarian surgery: a global surgery elective for senior
      medical students.
AB  - OBJECTIVES: The proportion of US medical students participating in global health
      has increased by 24%. These experiences are generally self-directed and lack a
      formal educational component. This article describes a structured, comprehensive,
      community-driven global surgery elective for senior-year students. DESIGN:
      "Surgery and Global Health" is a monthlong elective during which students shadow
      in the university hospital, lead discussions of an assigned text, attend
      lectures, and participate in a clinical rotation in rural Haiti. The first week
      is didactic and takes place in Atlanta, GA. Weeks 2 through 4 are clinical and
      are conducted in Haiti. Urological and general surgery procedures are performed
      during weeks 2 and 3, while the final week is reserved for follow-up care. This
      experience was institutionally supported. SETTING: Emory University Hospital,
      Atlanta, GA; L'Hopital St. Therese, Hinche, Centre, Haiti. PARTICIPANTS: Emory
      University School of Medicine students, years 2 through 4, supervised by faculty
      from the departments of Urology, General Surgery, and Anesthesiology. Senior-year
      students spent 21 days in central Haiti working in a rural clinical setting.
      RESULTS: Students participated in all facets of surgical care including
      preoperative clearance, postanesthesia care, discharge planning, and follow-up.
      Students felt a level of supervised responsibility that was not afforded at their
      home institution and were able to take on more advanced clinical roles.
      CONCLUSIONS: Students planned and executed this innovative experience with
      multidisciplinary, departmental, and institutional support. Stateside components
      introduced students to Haitian culture, global surgery ethics, and humanitarian
      surgical trip logistics. Structured global health experiences such as this give
      students practical skills and incentive to pursue careers involving global
      surgery.

PMID- 24913429
TI  - Using the American Board of Surgery In-Training Examination to predict board
      certification: a cautionary study.
AB  - OBJECTIVE: Although designed as a low-stakes formative examination, the American
      Board of Surgery In-Training Examination (ABSITE) is often used in high-stakes
      decisions such as promotion, remediation, and retention owing to its perceived
      ability to predict the outcome of board certification. Because of the discrepancy
      between intent and use, the ability of ABSITE scores to predict passing the
      American Board of Surgery certification examinations was analyzed. METHODS: All
      first-time American Board of Surgery qualifying examination (QE) examinees
      between 2006 and 2012 were reviewed. Examinees' postgraduate year (PGY) 1 and
      PGY5 ABSITE standard scores were linked to QE scores and pass/fail outcomes (n =
      6912 and 6846, respectively) as well as first-time certifying examination (CE)
      pass/fail results (n = 1329). Linear and logistic regression analyses were
      performed to evaluate the utility of ABSITE scores to predict board certification
      scores and pass/fail outcomes. RESULTS: PGY1 ABSITE scores accounted for 22% of
      the variance in QE scores (p < 0.001). PGY5 scores were a slightly better
      predictor, accounting for 30% of QE score variance (p < 0.001). Analyses showed
      that selecting a PGY5 ABSITE score that maximized overall decision accuracy for
      predicting QE pass/fail outcomes (86% accuracy) resulted in 98% sensitivity, 13%
      specificity, a positive predictive value of 87%, and a negative predictive value
      of 57%. ABSITE scores were not predictive of success on the CE. CONCLUSIONS:
      ABSITE scores are a useful predictor of QE scores and outcomes but do not predict
      passing the CE. Although scoring well on the ABSITE is highly predictive of QE
      success, using low ABSITE scores to predict QE failure results in frequent
      decision errors. Program directors and other evaluators should use additional
      sources of information when making high-stakes decisions about resident
      performance.

PMID- 24913431
TI  - Measurement-device-independent quantum key distribution for Scarani-Acin-Ribordy
      Gisin 04 protocol.
AB  - The measurement-device-independent quantum key distribution (MDI QKD) was
      proposed to make BB84 completely free from any side-channel in detectors. Like in
      prepare & measure QKD, the use of other protocols in MDI setting would be
      advantageous in some practical situations. In this paper, we consider SARG04
      protocol in MDI setting. The prepare & measure SARG04 is proven to be able to
      generate a key up to two-photon emission events. In MDI setting we show that the
      key generation is possible from the event with single or two-photon emission by a
      party and single-photon emission by the other party, but the two-photon emission
      event by both parties cannot contribute to the key generation. On the contrary to
      prepare & measure SARG04 protocol where the experimental setup is exactly the
      same as BB84, the measurement setup for SARG04 in MDI setting cannot be the same
      as that for BB84 since the measurement setup for BB84 in MDI setting induces too
      many bit errors. To overcome this problem, we propose two alternative
      experimental setups, and we simulate the resulting key rate. Our study highlights
      the requirements that MDI QKD poses on us regarding with the implementation of a
      variety of QKD protocols. 

PMID- 24913430
TI  - Sticky-trapping biting midges (Culicoides spp.) alighting on cattle and sheep:
      effects of trap colour and evidence for host preference.
AB  - Sticky traps were mounted on heifers and sheep to assess Culicoides spp.
      (Diptera: Ceratopogonidae) host preference. Initially, four coloured 200-cm(2)
      sticky traps (white, clear, yellow and blue) were attached to the backs of each
      of ten Friesian heifers that were released into open pasture for 24 h, repeated
      on six occasions. More Obsoletus group Culicoides were caught on the white and
      clear traps than on the yellow and blue. Trap position on the right or left flank
      also affected midge catch, probably due to heifer orientation in the field. Next,
      six Friesian heifers and six Charollais hoggets each had one clear and one white
      sticky strap attached to their backs for one 24-h period per week, repeated for
      24 weeks. Overall, Obsoletus group Culicoides comprised 91.8% (n = 5, 955) of the
      midge catch but there was no evidence of host preference, either discounting or
      including host live weight in the analyses. However, Pulicaris group Culicoides
      did demonstrate a significant host preference for sheep, providing that the
      analysis was adjusted for live weight. On heifers, the Pulicaris group comprised
      7.5% of biting midges caught, whereas on hoggets, it comprised 12.7%.

PMID- 24913432
TI  - Comparative analysis of quantitative reverse transcription real-time PCR and
      commercial enzyme imunoassays for detection of enterotoxigenic Bacillus
      thuringiensis isolates.
AB  - Entomopathogenic Bacillus thuringiensis is closely related to Bacillus cereus, a
      human pathogen known to cause emesis and diarrhea. Standard detection methods do
      not distinguish these bacilli. Hemolysin BL (hbl) and non-hemolytic enterotoxin
      (nhe) genes that encode, respectively, HBL and NHE enterotoxins, are known to be
      harbored in both bacterial species, suggesting that differentiation of these
      bacilli is clinically and epidemiologically relevant. In this study the
      reliability of quantitative reverse transcription real-time PCR (qRT-PCR) and
      enzyme immunoassays (EIAs) in detecting hbl and nhe transcripts and corresponding
      toxins in environmental B. thuringiensis isolates was assessed. At least one
      enterotoxin gene was present in each isolate, and nhe or hbl genes were found in
      85% and 55% of the strains, respectively. Based on statistical analyses, both
      BCET-RPLA and Duopath detected HBL at similar levels, and TECRA and Duopath can
      be used interchangeably for the detection of NHE, although TECRA has
      significantly lower sensitivity than Duopath. Thus, as potential enterotoxic B.
      thuringiensis strains occur in the natural environment, and EIA results may not
      correspond with the presence of enterotoxin genes and their expression, we
      suggest that reliable interpretation will be significantly enhanced by including
      qRT-PCR to support inferences based on EIAs.

PMID- 24913433
TI  - 5-Aminolevulinic acid-loaded fullerene nanoparticles for in vitro and in vivo
      photodynamic therapy.
AB  - This report explores some properties of 80-200 nm nanoparticles containing 5
      aminolevulinic acid (ALA) and fullerene (C60) for photodynamic therapy (PDT).
      Compared with ALA, the nanoparticles yielded more protoporphyrin IX (PpIX)
      formation in cells and tissues and to a significant improvement in antitumor
      efficacy in tumor-bearing mice. Maximum levels of PpIX were obtained 4 h after
      administration and selective PpIX formation in tumor was observed. These
      nanoparticles appear to be a useful vehicle for drug delivery purposes. In this
      study, a procedure for preparing fullerene nanoparticles containing ALA was
      developed. The product alone exhibited no detectable toxicity in the dark and was
      superior to ALA alone in promoting PpIX biosynthesis and PDT efficacy both in
      culture and in a murine tumor model. These results suggest that this procedure
      could be the basis for an improved PDT protocol for cancer control. 

PMID- 24913434
TI  - A case-control study of patients with squamous cell carcinoma of the oral cavity
      and oropharynx treated with pulsed-dose-rate brachytherapy.
AB  - PURPOSE: Pulsed-dose-rate (PDR) brachytherapy is thought to mimic the
      radiobiological benefits of continuous low-dose-rate (cLDR) delivery but is safer
      for medical personnel. We set out to evaluate the outcomes of this technique in
      patients with head and neck squamous cell carcinoma. METHODS AND MATERIALS: A
      total of 36 consecutive patients treated with PDR brachytherapy were randomly
      matched to 72 cLDR controls according to T-stage, tumor site, and management
      strategy. Local recurrence and late complications were compared between the two
      groups. RESULTS: Baseline characteristics were similar in both groups. Oral
      cavity cancers predominated at 81%, and 89% had T1/T2 tumors. Seventy-five
      percent of patients underwent surgery before radiation treatment. Median followup
      was 59 and 30 months for cLDR and PDR patients, respectively. Three-year
      actuarial local recurrence-free survival was 97% and 94% for cLDR and PDR
      patients, respectively (p = 0.77). Three-year cumulative risk of Grade >=2
      complications was 45% and 32% for cLDR and PDR patients, respectively (p = 0.2).
      For cLDR, a dose rate exceeding 68 cGy/h resulted in more complications (RR 5.3,
      p < 0.05). Similarly, PDR patients receiving >=75 cGy/pulse were at higher risk.
      CONCLUSIONS: PDR brachytherapy in head and neck squamous cell carcinoma yields
      comparable results to cLDR treatment. Dose rate was correlated with the risk of
      late complications, regardless of technique.

PMID- 24913435
TI  - Investigation of interseed attenuation and tissue composition effects in (125)I
      seed implant prostate brachytherapy.
AB  - PURPOSE: To use Monte Carlo (MC) simulation and sector analysis to assess
      interseed attenuation and scatter (ISA) and tissue effects in permanent seed
      implant prostate brachytherapy and to compare methods for modeling tissue.
      METHODS AND MATERIALS: CT-based postimplant plan simulations for 40 patients were
      evaluated using dose-volume histogram (DVH) parameters and sector analysis.
      Simulations in water (to evaluate ISA alone) and tissue assigned from contours or
      CT data, with and without calcifications, were compared. RESULTS: For patients
      without calcifications, mean combined ISA and tissue effect reduced prostate D90
      by 4.2 Gy (2.9%), prostate V100 by 0.5 cm(3) (1.4%), urethra D10 by 8.6 Gy
      (3.5%), rectal [Formula: see text] by 11.6 Gy (10.5%), and the 100% isodose
      volume by 4.7 cm(3). Larger differences were observed comparing planned dose to
      postimplant, mean prostate D90 reduced from 185 to 149.8 Gy (-19%). For patients
      with calcifications, larger tissue effects were observed, prostate D90 reduced by
      up to 7.4%. Sector analysis showed dose reductions were larger in anterior and
      base sectors of the prostate. For patients without calcifications, contour- and
      CT-based tissue model results agreed within <0.5% for all DVH parameters, with up
      to 4% difference for patients with calcifications. CONCLUSIONS: Advanced
      brachytherapy dose calculation methods that take account of ISA and tissue
      effects show that clinical (125)I implant dose is different from TG-43U1 (AAPM
      Task Group No. 43 Report-Update 1) calculations, reducing DVH parameter values
      particularly for patients with calcifications. Peripheral dose and areas of the
      implant with relatively poorer coverage are particularly affected. However, dose
      reductions are small compared with other postimplant dose uncertainties.

PMID- 24913436
TI  - A prospective study of suicidal ideation in posttraumatic stress disorder: the
      role of perceptions of defeat and entrapment.
AB  - OBJECTIVES: This study aimed to provide the first prospective test of the ability
      of defeat and entrapment to predict suicidal ideation in posttraumatic stress
      disorder (PTSD) after controlling for the effects of PTSD severity, comorbid
      depressive symptoms, and hopelessness on suicidal ideation. METHODS: Participants
      were 52 individuals diagnosed with PTSD. Baseline and follow-up assessments were
      13 to 15 months apart. Defeat and entrapment were conceptualized and analyzed as
      a unique construct (defeat/entrapment) in this study. Multiple regression
      analysis was applied to examine the predictive effects of defeat/entrapment on
      suicidal ideation. RESULTS: Defeat/entrapment scores predicted changes in the
      levels of suicidal ideation at follow-up while controlling for baseline suicidal
      ideation, PTSD severity, comorbid depressive symptoms, and hopelessness.
      CONCLUSIONS: These outcomes provide support to contemporary models of suicidality
      that suggest that defeat/entrapment is a strong predictor of suicidality in PTSD.

PMID- 24913437
TI  - Editorial comment from Dr Tanaka to Non-bladder conditions in female Taiwanese
      patients with interstitial cystitis/hypersensitive bladder syndrome.

PMID- 24913438
TI  - Getting added value from using qualitative research with randomized controlled
      trials: a qualitative interview study.
AB  - BACKGROUND: Qualitative research is undertaken with randomized controlled trials
      of health interventions. Our aim was to explore the perceptions of researchers
      with experience of this endeavour to understand the added value of qualitative
      research to the trial in practice. METHODS: A telephone semi-structured interview
      study with 18 researchers with experience of undertaking the trial and/or the
      qualitative research. RESULTS: Interviewees described the added value of
      qualitative research for the trial, explaining how it solved problems at the
      pretrial stage, explained findings, and helped to increase the utility of the
      evidence generated by the trial. From the interviews, we identified three models
      of relationship of the qualitative research to the trial. In 'the peripheral'
      model, the trial was an opportunity to undertake qualitative research, with no
      intention that it would add value to the trial. In 'the add-on' model, the
      qualitative researcher understood the potential value of the qualitative research
      but it was viewed as a separate and complementary endeavour by the trial lead
      investigator and wider team. Interviewees described how this could limit the
      value of the qualitative research to the trial. Finally 'the integral' model
      played out in two ways. In 'integral-in-theory' studies, the lead investigator
      viewed the qualitative research as essential to the trial. However, in practice
      the qualitative research was under-resourced relative to the trial, potentially
      limiting its ability to add value to the trial. In 'integral-in-practice'
      studies, interviewees described how the qualitative research was planned from the
      beginning of the study, senior qualitative expertise was on the team from
      beginning to end, and staff and time were dedicated to the qualitative research.
      In these studies interviewees described the qualitative research adding value to
      the trial although this value was not necessarily visible beyond the original
      research team due to the challenges of publishing this research. CONCLUSIONS:
      Health researchers combining qualitative research and trials viewed this practice
      as strengthening evaluative research. Teams viewing the qualitative research as
      essential to the trial, and resourcing it in practice, may have a better chance
      of delivering its added value to the trial.

PMID- 24913440
TI  - Ligament strain on the iliofemoral, pubofemoral, and ischiofemoral ligaments in
      cadaver specimens: biomechanical measurement and anatomical observation.
AB  - The iliofemoral, pubofemoral, and ischiofemoral ligaments are major structures
      that stabilize the hip joint. We have sought evidence on which to base more
      effective hip stretching positions. The purpose of this study was to measure
      strains on these ligaments and to observe them. Eight fresh/frozen translumbar
      cadaver specimens were used. Clinically available stretching positions for these
      ligaments were adopted. Strain on each ligament was measured by a displacement
      sensor during passive torque to the hip joint. Hip motion was measured using an
      electromagnetic tracking device. The strained ligaments were captured on clear
      photographs. Significantly, high strains were imposed on the superior iliofemoral
      ligament by external rotation of the hip (3.48%); on the inferior iliofemoral
      ligament by maximal extension and 10 degrees  or 20 degrees  of external rotation
      with maximal extension (1.86%, 1.46%, 1.25%); on the pubofemoral ligament by
      maximal abduction and 10 degrees , 20 degrees , or 30 degrees  of external
      rotation with maximal abduction (3.18%, 3.28%, 3.11%, 2.99%); and on the
      ischiofemoral ligament by 10 degrees  or 20 degrees  of abduction with maximal
      internal rotation (7.11%, 7.83%). Fiber direction in each ligament was clearly
      identified. Significantly, high strains on hip ligaments corresponded with the
      anatomical direction of the ligament fibers. Positions were identified for each
      ligament that imposed maximal increase in strain on it.

PMID- 24913441
TI  - Performance of different three-dimensional scaffolds for in vivo endochondral
      bone generation.
AB  - In the context of skeletal tissue development and repair, endochondral
      ossification has inspired a new approach to regenerate bone tissue in vivo using
      a cartilage intermediate as an osteoinductive template. The aim of this study was
      to investigate the behavior of mesenchymal stem cells (MSCs) in regard to in
      vitro cartilage formation and in vivo bone regeneration when combined with
      different three-dimensional (3D) scaffold materials, i.e.,
      hydroxyapatite/tricalcium phosphate (HA/TCP) composite block, polyurethane (PU)
      foam, poly(lactic-co-glycolic acid)/poly(epsilon-caprolactone) electrospun fibers
      (PLGA/PCL) and collagen I gel. To this end, rat MSCs were seeded on these
      scaffolds and chondrogenically differentiated in vitro for 4 weeks followed by in
      vivo subcutaneous implantation for 8 weeks. Nonetheless, the quality and maturity
      of in vivo ectopic bone formation appeared to be scaffold/material-dependent.
      Eight weeks of implantation was not sufficient to ossify the entire PLGA/PCL
      constructs, albeit a comprehensive remodeling of the cartilage had occurred. For
      HA/TCP, PU and collagen I scaffolds, more mature bone formation with rich
      vascularity and marrow stroma development could be observed. These data suggest
      that chondrogenic priming of MSCs in the presence of different scaffold materials
      allows the establishment of reliable templates for generating functional
      endochondral bone tissue in vivo without using osteoinductive growth factors. The
      morphology and maturity of bone formation. 

PMID- 24913444
TI  - Racial/ethnic differences in the presentation and management of severe
      bronchiolitis.
AB  - BACKGROUND AND OBJECTIVE: Bronchiolitis is the leading cause of hospitalization
      for US infants and is associated with increased risk of childhood asthma.
      Although studies have shown differences in the presentation and management of
      asthma across race/ethnicity, it is unclear if such differences are present for
      bronchiolitis. We examined if racial/ethnic differences exist in the presentation
      and management of severe bronchiolitis. METHODS: We performed a 16-center,
      prospective cohort study from 2007 to 2010. Children <2 years old hospitalized
      with a diagnosis of bronchiolitis were included. A structured interview, chart
      review, and 1-week phone follow-up were completed. Multivariable logistic
      regression was used to examine the independent association between race/ethnicity
      and diagnostic imaging, treatment (eg, albuterol, corticosteroids, and continuous
      positive airway pressure/intubation), management (eg, intensive care unit
      admission and length of stay), discharge on inhaled corticosteroids, and
      bronchiolitis relapse. RESULTS: Among 2130 patients, 818 (38%) were non-Hispanic
      white (NHW), 511 (24%) were non-Hispanic black (NHB), and 801 (38%) were
      Hispanic. Compared with all groups, NHB children were most likely to receive
      albuterol before admission (odds ratio [OR]: 1.58; 95% confidence interval [CI]:
      1.20-2.07) and least likely to receive chest x-rays during hospitalization (OR:
      0.66; 95% CI: 0.49-0.90). Hispanic children were most likely to be discharged on
      inhaled corticosteroids (OR: 1.92; 95% CI: 1.19-3.10). CONCLUSION: We observed
      differences between NHW and minority children regarding preadmission albuterol
      use, inpatient diagnostic imaging, and prescription of inhaled corticosteroids at
      discharge, practices that deviate from the American Academy of Pediatrics
      guidelines. The causes of these differences require further study, but they
      support implementation of care pathways for severe bronchiolitis.

PMID- 24913443
TI  - Altered beta1,6-GlcNAc branched N-glycans impair TGF-beta-mediated epithelial-to
      mesenchymal transition through Smad signalling pathway in human lung cancer.
AB  - The change of oligosaccharide structure has been revealed to be crucial for
      glycoproteins' biological functions and cell biological characteristics. N
      acetylglucosaminy transferase V (GnT-V), a key enzyme catalysing the reaction of
      adding beta1, 6-N-acetylglucosamine (GlcNAc) on asparagine-linked
      oligosaccharides of cell proteins, has been implicated to a metastastic-promoting
      oncoprotein in some carcinomas. However, this correlation might not be subjected
      to all types of cancers, for example, in non-small cell lung cancers, low level
      of GnT-V expression is associated with relatively short survival time and poor
      prognosis. To explain the role of GnT-V in lung cancer progression, we studied
      the association of GnT-V expression with lung cancer EMT behaviour. We found that
      GnT-V expression was correlated with epithelial marker positively and mesenchymal
      marker negatively. GnT-V levels, as well as beta1,6-GlcNAc branched N-glycans,
      were strongly reduced in TGF-beta1-induced EMT of human lung adenocarcinoma A549
      cells. Further studies showed that suppression of beta1,6-GlcNAc branched N
      glycans by inhibitor or GnT-V silencing in A549 cells could promote TGF-beta1
      induced EMT-like changes, cell migration and invasion. Meanwhile, overexpression
      of GnT-V impaired TGF-beta1-induced EMT, migration and invasion. It suggests that
      GnT-V suppresses the EMT process of lung cancer cells through inhibiting the TGF
      beta/Smad signalling and its downstream transcription factors in a GnT-V
      catalytic activity-dependent manner. Taken together, the present study reveals a
      novel mechanism of GnT-V as a suppressor of both EMT and invasion in human lung
      cancer cells, which may be useful for fully understanding N-glycan's biological
      roles in lung cancer progression. 

PMID- 24913445
TI  - Molecular basis of agonist docking in a human GPR103 homology model by site
      directed mutagenesis and structure-activity relationship studies.
AB  - BACKGROUND AND PURPOSE: The neuropeptide 26RFa and its cognate receptor GPR103
      are involved in the control of food intake and bone mineralization. Here, we have
      tested, experimentally, the predicted ligand-receptor interactions by site
      directed mutagenesis of GPR103 and designed point-substituted 26RFa analogues.
      EXPERIMENTAL APPROACH: Using the X-ray structure of the beta2 -adrenoceptor, a 3
      D molecular model of GPR103 has been built. The bioactive C-terminal octapeptide
      26RFa(19-26) , KGGFSFRF-NH2 , was docked in this GPR103 model and the ligand
      receptor complex was submitted to energy minimization. KEY RESULTS: In the most
      stable complex, the Phe-Arg-Phe-NH2 part was oriented inside the receptor cavity,
      whereas the N-terminal Lys residue remained outside. A strong intermolecular
      interaction was predicted between the Arg(25) residue of 26RFa and the Gln(125)
      residue located in the third transmembrane helix of GPR103. To confirm this
      interaction experimentally, we tested the ability of 26RFa and Arg-modified 26RFa
      analogues to activate the wild-type and the Q125A mutant receptors transiently
      expressed in CHO cells. 26RFa (10(-6)  M) enhanced [Ca(2+) ]i in wild-type GPR103
      transfected cells, but failed to increase [Ca(2+) ]i in Q125A mutant receptor
      expressing cells. Moreover, asymmetric dimethylation of the side chain of
      arginine led to a 26RFa analogue, [ADMA(25) ]26RFa(20-26) , that was unable to
      activate the wild-type GPR103, but antagonized 26RFa-evoked [Ca(2+) ]i increase.
      CONCLUSION AND IMPLICATIONS: Altogether, these data provide strong evidence for a
      functional interaction between the Arg(25) residue of 26RFa and the Gln(125)
      residue of GPR103 upon ligand-receptor activation, which can be exploited for the
      rational design of potent GPR103 agonists and antagonists.

PMID- 24913446
TI  - Can we continue to neglect genomic variation in introgression rates when
      inferring the history of speciation? A case study in a Mytilus hybrid zone.
AB  - The use of molecular data to reconstruct the history of divergence and gene flow
      between populations of closely related taxa represents a challenging problem. It
      has been proposed that the long-standing debate about the geography of speciation
      can be resolved by comparing the likelihoods of a model of isolation with
      migration and a model of secondary contact. However, data are commonly only fit
      to a model of isolation with migration and rarely tested against the secondary
      contact alternative. Furthermore, most demographic inference methods have
      neglected variation in introgression rates and assume that the gene flow
      parameter (Nm) is similar among loci. Here, we show that neglecting this source
      of variation can give misleading results. We analysed DNA sequences sampled from
      populations of the marine mussels, Mytilus edulis and M. galloprovincialis,
      across a well-studied mosaic hybrid zone in Europe and evaluated various
      scenarios of speciation, with or without variation in introgression rates, using
      an Approximate Bayesian Computation (ABC) approach. Models with heterogeneous
      gene flow across loci always outperformed models assuming equal migration rates
      irrespective of the history of gene flow being considered. By incorporating this
      heterogeneity, the best-supported scenario was a long period of allopatric
      isolation during the first three-quarters of the time since divergence followed
      by secondary contact and introgression during the last quarter. By contrast,
      constraining migration to be homogeneous failed to discriminate among any of the
      different models of gene flow tested. Our simulations thus provide statistical
      support for the secondary contact scenario in the European Mytilus hybrid zone
      that the standard coalescent approach failed to confirm. Our results demonstrate
      that genomic variation in introgression rates can have profound impacts on the
      biological conclusions drawn from inference methods and needs to be incorporated
      in future studies. 

PMID- 24913447
TI  - SMARTPOP: inferring the impact of social dynamics on genetic diversity through
      high speed simulations.
AB  - BACKGROUND: Social behavior has long been known to influence patterns of genetic
      diversity, but the effect of social processes on population genetics remains
      poorly quantified - partly due to limited community-level genetic sampling (which
      is increasingly being remedied), and partly to a lack of fast simulation software
      to jointly model genetic evolution and complex social behavior, such as marriage
      rules. RESULTS: To fill this gap, we have developed SMARTPOP - a fast, forward-in
      time genetic simulator - to facilitate large-scale statistical inference on
      interactions between social factors, such as mating systems, and population
      genetic diversity. By simultaneously modeling genetic inheritance and dynamic
      social processes at the level of the individual, SMARTPOP can simulate a wide
      range of genetic systems (autosomal, X-linked, Y chromosomal and mitochondrial
      DNA) under a range of mating systems and demographic models. Specifically
      designed to enable resource-intensive statistical inference tasks, such as
      Approximate Bayesian Computation, SMARTPOP has been coded in C++ and is heavily
      optimized for speed and reduced memory usage. CONCLUSION: SMARTPOP rapidly
      simulates population genetic data under a wide range of demographic scenarios and
      social behaviors, thus allowing quantitative analyses to address complex socio
      ecological questions.

PMID- 24913449
TI  - Screening and functional analysis of glioma-related genes induced by candoxin.
AB  - This study aimed to identify time-specific and common differential genes (CDGs)
      expressed in glioma cells following exposure to candoxin at three different time
      points. Gene expression data from candoxin-treated human glioma (Hs 683) cells
      were downloaded from the Gene Expression Omnibus database (accession number,
      GSE1682), from a 12-time-point set of samples. Differentially expressed genes
      were screened between control and candoxin-treated samples at different time
      points, and three time-specific gene sets and CDGs were identified. All genes
      were subject to pathway enrichment analysis to gain further insight into gene
      function. CDGs were clustered based upon their original expression between 0 and
      48 h, and, from this subset, feature genes were selected. Small molecules
      associated with candoxin were identified by comparing the expression pattern of
      the most valid candidate genes with that of differential genes exposed to small
      molecules in the Connectivity Map. From the 12-, 24- and 48-h time-points, 746,
      265 and 539 differentially expressed genes were identified, respectively. A total
      of 129 genes were differentially expressed and significantly enriched in focal
      adhesion and gap junction pathways. From these, 11 feature genes and one marker
      gene (EPS8L1) were identified. Four small molecules that were most relevant to
      candoxin action were identified. In conclusion, it is hypothesized that candoxin
      stimulation can cause glial inflammation through mutations in cell adhesion
      activity. The EPS8L1 gene may be a valid marker for glioma diagnosis, and the
      four small molecules identified may be relevant for future drug design. 

PMID- 24913448
TI  - LASP1 is a novel BCR-ABL substrate and a phosphorylation-dependent binding
      partner of CRKL in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is characterized by a genomic translocation
      generating a permanently active BCR-ABL oncogene with a complex pattern of
      atypically tyrosine-phosphorylated proteins that drive the malignant phenotype of
      CML. Recently, the LIM and SH3 domain protein 1 (LASP1) was identified as a
      component of a six gene signature that is strongly predictive for disease
      progression and relapse in CML patients. However, the underlying mechanisms why
      LASP1 expression correlates with dismal outcome remained unresolved. Here, we
      identified LASP1 as a novel and overexpressed direct substrate of BCR-ABL in CML.
      We demonstrate that LASP1 is specifically phosphorylated by BCR-ABL at tyrosine
      171 in CML patients, which is abolished by tyrosine kinase inhibitor therapy.
      Further studies revealed that LASP1 phosphorylation results in an association
      with CRKL - another specific BCR-ABL substrate and bona fide biomarker for BCR
      ABL activity. pLASP1-Y171 binds to non-phosphorylated CRKL at its SH2 domain.
      Accordingly, the BCR-ABL-mediated pathophysiological hyper-phosphorylation of
      LASP1 in CML disrupts normal regulation of CRKL and LASP1, which likely has
      implications on downstream BCR-ABL signaling. Collectively, our results suggest
      that LASP1 phosphorylation might serve as an additional candidate biomarker for
      assessment of BCR-ABL activity and provide a first step toward a molecular
      understanding of LASP1 function in CML.

PMID- 24913450
TI  - Increased waist circumference is independently associated with hypothyroidism in
      Mexican Americans: replicative evidence from two large, population-based studies.
AB  - BACKGROUND: Mexican Americans are at an increased risk of both thyroid
      dysfunction and metabolic syndrome (MS). Thus it is conceivable that some
      components of the MS may be associated with the risk of thyroid dysfunction in
      these individuals. Our objective was to investigate and replicate the potential
      association of MS traits with thyroid dysfunction in Mexican Americans. METHODS:
      We conducted association testing for 18 MS traits in two large studies on Mexican
      Americans - the San Antonio Family Heart Study (SAFHS) and the National Health
      and Nutrition Examination Survey (NHANES) 2007-10. A total of 907 participants
      from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007-10
      were included in this study. The outcome measures were prevalence of clinical and
      subclinical hypothyroidism and thyroid function index (TFI) - a measure of
      thyroid function. For the SAFHS, we used polygenic regression analyses with
      multiple covariates to test associations in setting of family studies. For the
      NHANES 2007-10, we corrected for the survey design variables as needed for
      association analyses in survey data. In both datasets, we corrected for age, sex
      and their linear and quadratic interactions. RESULTS: TFI was an accurate
      indicator of clinical thyroid status (area under the receiver-operating
      characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and
      NHANES 2007-10. Of the 18 MS traits, waist circumference (WC) showed the most
      consistent association with TFI in both studies independently of age, sex and
      body mass index (BMI). In the SAFHS and NHANES 2007-10 datasets, each standard
      deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p <
      0.001) unit increase in the TFI, respectively. In a series of polygenic and
      linear regression models, central obesity (defined as WC >= 102 cm in men and
      >=88 cm in women) was associated with clinical and subclinical hypothyroidism
      independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated
      prevalence of hypothyroidism was consistently high in those with central obesity,
      especially below 45y of age. CONCLUSIONS: WC independently associates with
      increased risk of thyroid dysfunction. Use of WC to identify Mexican American
      subjects at high risk of thyroid dysfunction should be investigated in future
      studies.

PMID- 24913451
TI  - Effect of improving the usability of an e-learning resource: a randomized trial.
AB  - Optimizing the usability of e-learning materials is necessary to reduce
      extraneous cognitive load and maximize their potential educational impact.
      However, this is often neglected, especially when time and other resources are
      limited. We conducted a randomized trial to investigate whether a usability
      evaluation of our multimedia e-learning resource, followed by fixing of all
      problems identified, would translate into improvements in usability parameters
      and learning by medical residents. Two iterations of our e-learning resource
      [version 1 (V1) and version 2 (V2)] were compared. V1 was the first fully
      functional version and V2 was the revised version after all identified usability
      problems were addressed. Residents in internal medicine and anesthesiology were
      randomly assigned to one of the versions. Usability was evaluated by having
      participants complete a user satisfaction questionnaire and by recording and
      analyzing their interactions with the application. The effect on learning was
      assessed by questions designed to test the retention and transfer of knowledge.
      Participants reported high levels of satisfaction with both versions, with good
      ratings on the System Usability Scale and adjective rating scale. In contrast,
      analysis of video recordings revealed significant differences in the occurrence
      of serious usability problems between the two versions, in particular in the
      interactive HandsOn case with its treatment simulation, where there was a median
      of five serious problem instances (range: 0-50) recorded per participant for V1
      and zero instances (range: 0-1) for V2 (P < 0.001). There were no differences in
      tests of retention or transfer of knowledge between the two versions. In
      conclusion, usability evaluation followed by a redesign of our e-learning
      resource resulted in significant improvements in usability. This is likely to
      translate into improved motivation and willingness to engage with the learning
      material. In this population of relatively high-knowledge participants, learning
      scores were similar across the two versions. 

PMID- 24913452
TI  - Performance of first-year health sciences students in a large, diverse,
      multidisciplinary, first-semester, physiology service module.
AB  - Health Science students at the University of KwaZulu-Natal perform better in
      their professional modules compared with their physiology modules. The pass rates
      of physiology service modules have steadily declined over the years. While a
      system is in place to identify "at-risk" students, it is only activated after the
      first semester. As a result, it is only from the second semester of their first
      year studies onward that at-risk students can be formally assisted. The challenge
      is thus to devise an appropriate strategy to identify struggling students earlier
      in the semester. Using questionnaires, students were asked about attendance,
      financing of their studies, and relevance of physiology. After the first class
      test, failing students were invited to complete a second questionnaire. In
      addition, demographic data were also collected and analyzed. Correlation analyses
      were undertaken of performance indicators based on the demographical data
      collected. The 2011 class comprised mainly sport science students (57%). The pass
      rate of sport science students was lower than the pass rates of other students
      (42% vs. 70%, P < 0.001). Most students were positive about physiology and
      recognized its relevance. Key issues identified were problems understanding
      concepts and terminology, poor study environment and skills, and lack of
      matriculation biology. The results of the first class test and final module marks
      correlated well. It is clear from this study that student performance in the
      first class test is a valuable tool to identify struggling students and that
      appropriate testing should be held as early as possible. 

PMID- 24913453
TI  - Expanding application of the Wiggers diagram to teach cardiovascular physiology.
AB  - Dr. Carl Wiggers' careful observations have provided a meaningful resource for
      students to learn how the heart works. Throughout the many years from his initial
      reports, the Wiggers diagram has been used, in various degrees of complexity, as
      a fundamental tool for cardiovascular instruction. Often, the various electrical
      and mechanical plots are the novice learner's first exposure to simulated data.
      As the various temporal relationships throughout a heartbeat could simply be
      memorized, the challenge for the cardiovascular instructor is to engage the
      learner so the underlying mechanisms governing the changing electrical and
      mechanical events are truly understood. Based on experience, we suggest some
      additions to the Wiggers diagram that are not commonly used to enhance
      cardiovascular pedagogy. For example, these additions could be, but are not
      limited to, introducing the concept of energy waves and their role in influencing
      pressure and flow in health and disease. Also, integrating concepts of exercise
      physiology, and the differences in cardiac function and hemodynamics between an
      elite athlete and normal subject, can have a profound impact on student
      engagement. In describing the relationship between electrical and mechanical
      events, the instructor may find the introduction of premature ventricular
      contractions as a useful tool to further understanding of this important
      principle. It is our hope that these examples can aid cardiovascular instructors
      to engage their learners and promote fundamental understanding at the expense of
      simple memorization. 

PMID- 24913454
TI  - Modern communication: exploring physiological transmission through tech-savvy
      analogies.

PMID- 24913455
TI  - Birds of a feather flock together: the importance of seating location with active
      learning in the professional classroom.

PMID- 24913456
TI  - A simple model of the accommodating lens of the human eye.

PMID- 24913457
TI  - Having fun and accepting challenges are natural instincts: jigsaw puzzles to
      challenge students and test their abilities while having fun!

PMID- 24913458
TI  - The synaptic challenge.

PMID- 24913459
TI  - Workshop report on "Linking Teaching and Learning Physiology" in Colombo, Sri
      Lanka (Nov. 7-8, 2012).

PMID- 24913460
TI  - Long-term subjective tongue function after partial glossectomy.
AB  - There have been limited studies of subjective tongue function over long-term
      follow-up in spite of swallowing and articulation disorders are common
      complications of glossectomy. To assess long-term subjective swallowing and
      articulation function after partial glossectomy. A total of 63 patients with the
      mobile tongue cancer who underwent partial glossectomy without reconstruction
      were interviewed to score their swallowing and articulation function on a 100
      point scale. The relation of this subjective scoring to the perioperative data
      was subjected to multivariate analysis. The mean patient age was 53.4 (19-81)
      years, and the mean follow-up duration was 78.9 (14-277) months. Mean swallowing
      and articulation function score was 87.7 +/- 6.1 and 88.6 +/- 5.4. Age, follow-up
      duration, T stage and resection volume were significantly correlated with
      swallowing function (P = 0.026, 0.029, 0.016, 0.002, respectively); follow-up
      duration was correlated with articulation function (P = 0.039). Patients who
      undergo partial glossectomy without reconstruction generally demonstrate good
      function on long-term follow-up. Subjective dysfunction was correlated with
      larger resection volume, older age and shorter follow-up duration. 

PMID- 24913461
TI  - Field assessment of balance in 10 to 14 year old children, reproducibility and
      validity of the Nintendo Wii board.
AB  - BACKGROUND: Because body proportions in childhood are different to those in
      adulthood, children have a relatively higher centre of mass location. This
      biomechanical difference and the fact that children's movements have not yet
      fully matured result in different sway performances in children and adults. When
      assessing static balance, it is essential to use objective, sensitive tools, and
      these types of measurement have previously been performed in laboratory settings.
      However, the emergence of technologies like the Nintendo Wii Board (NWB) might
      allow balance assessment in field settings. As the NWB has only been validated
      and tested for reproducibility in adults, the purpose of this study was to
      examine reproducibility and validity of the NWB in a field setting, in a
      population of children. METHODS: Fifty-four 10-14 year-olds from the CHAMPS-Study
      DK performed four different balance tests: bilateral stance with eyes open (1),
      unilateral stance on dominant (2) and non-dominant leg (3) with eyes open, and
      bilateral stance with eyes closed (4). Three rounds of the four tests were
      completed with the NWB and with a force platform (AMTI). To assess
      reproducibility, an intra-day test-retest design was applied with a two-hour
      break between sessions. RESULTS: Bland-Altman plots supplemented by Minimum
      Detectable Change (MDC) and concordance correlation coefficient (CCC)
      demonstrated satisfactory reproducibility for the NWB and the AMTI (MDC: 26.3
      28.2%, CCC: 0.76-0.86) using Centre Of Pressure path Length as measurement
      parameter. Bland-Altman plots demonstrated satisfactory concurrent validity
      between the NWB and the AMTI, supplemented by satisfactory CCC in all tests (CCC:
      0.74-0.87). The ranges of the limits of agreement in the validity study were
      comparable to the limits of agreement of the reproducibility study. CONCLUSION:
      Both NWB and AMTI have satisfactory reproducibility for testing static balance in
      a population of children. Concurrent validity of NWB compared with AMTI was
      satisfactory. Furthermore, the results from the concurrent validity study were
      comparable to the reproducibility results of the NWB and the AMTI. Thus, NWB has
      the potential to replace the AMTI in field settings in studies including
      children. Future studies are needed to examine intra-subject variability and to
      test the predictive validity of NWB.

PMID- 24913462
TI  - Longitudinal changes in maternal soluble endoglin and angiopoietin-2 in women at
      risk for pre-eclampsia.
AB  - OBJECTIVE: To investigate longitudinal changes in maternal plasma levels of
      soluble endoglin (sEng) and angiopoietin-2 (Ang-2) in pregnant women who develop
      pre-eclampsia (PE) and gestational hypertension (GH). METHODS: This was a nested
      case-control study drawn from a larger prospective longitudinal study in
      singleton pregnancies identified by screening at 11 + 0 to 13 + 6 weeks'
      gestation as being at high-risk for PE. Blood samples were taken every 4 weeks
      until delivery. Values were compared in women who developed preterm PE (requiring
      delivery before 37 weeks), term PE, GH and those who remained normotensive.
      RESULTS: A total of 471 samples were analyzed in 122 women, comprising 85 who
      remained normotensive, 12 who developed GH, 13 who developed term PE and 12 who
      developed preterm PE. In the normotensive group, there was an increase in log10
      sEng levels with gestational age. In the preterm PE group, compared with the
      normotensive group, sEng was higher from 18 weeks onwards, and the difference
      increased significantly with gestational age (P < 0.001). In the GH and term PE
      groups, sEng did not differ significantly from that of the normotensive group (P
      = 0.583 and P = 0.890, respectively). The square root of Ang-2 decreased
      significantly with gestational age, but did not differ significantly among the
      different outcome groups (P = 0.571). CONCLUSION: Maternal plasma sEng, but not
      Ang-2, may be a useful mid- and late-gestation biomarker for the development of
      PE.

PMID- 24913463
TI  - Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high
      sensitivity C-reactive protein and tumor necrosis factor-alpha in a rat
      endometriosis model.
AB  - PURPOSE: The purpose of this study was to examine the effects of atorvastatin in
      the treatment of experimental endometriosis. METHODS: Endometriosis was induced
      in 24 female rats. 4 weeks after the procedure dimensions of the foci were
      recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose
      of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a
      single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The
      rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the
      treatment, laparotomy was performed, and the dimensions of the endometriotic foci
      were recorded. Biochemical, histopathological and immunohistochemical studies
      were performed and nociception was compared in groups. RESULTS: Atorvastatin
      treatment exhibited significant analgesic activity in hot plate model (P =
      0.022). The serum hs-CRP and tumor necrosis TNF-alpha levels were similar between
      the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant
      decrease in both serum markers. The histological and immunohistochemical scores
      were also found to be markedly lower in Group 1 and Group 2 (P < 0.05).
      CONCLUSION: Atorvastatin treatment may have a therapeutic potential in the
      treatment of endometriosis through its anti-inflammatory and anti-nociceptive
      properties.

PMID- 24913464
TI  - Establishment of recipient model for spermatogonial stem cells transplantation in
      Kunming mice.
AB  - The objective of this study was to establish a recipient model for spermatogonial
      stem cells (SSCs) transplantation in the Kunming mice after different doses
      busulfan treatment. The results showed that the most optimal dose of busulfan was
      20mg/kg and the most appropriate time for transplantation was 5-7 wk after
      busulfan treatment. Then, the cloned fragments existed in the testis of recipient
      mice after 20mg/kg busulfan treatment and the offspring with enhanced green
      fluorescent protein (EGFP) were produced by the transplanting SSCs. Hence, we
      established the effective recipient model for donor-derived SSCs transplantation
      in Kunming mice.

PMID- 24913465
TI  - Urine 2DE proteome analysis in healthy condition and kidney disease.
AB  - Urine is a source of potential markers of disease. In the context of renal
      disease, urine is particularly important as it may directly reflect kidney
      injury. Current markers of renal dysfunction lack both optimal specificity and
      sensitivity, and improved technologies and approaches are needed. There is no
      clear consensus about the best sample pretreatment procedure for 2DE analysis of
      the urine proteome. Sample pretreatment conditions spots resolution and detection
      sensitivity, critically. As a first goal, we exhaustively compared eight
      different sample cleaning and protein purification methodologies for 2DE analysis
      of urine from healthy individuals. Oasis(r) HLB cartridges allowed the detection
      of the highest number of low molecular weight proteins; while PD10 desalting
      columns resulted in the highest number of detected spots in the high molecular
      weight area. Sample pretreatment strategies were also explored in the context of
      proteinuria, a clinical condition often associated to renal damage. Testing of
      urine samples from 13 patients with hypertension or kidney disease and different
      levels of proteinuria identified Oasis(r) HLB cartridge purification in
      combination with albumin depletion by ProteoPrep kit as the best option for urine
      proteome profiling from patients with proteinuric (> 30 mg/L albumin in urine)
      renal disease.

PMID- 24913466
TI  - A single-gradient junction technique to replace multiple-junction shifts for
      craniospinal irradiation treatment.
AB  - Craniospinal irradiation (CSI) requires abutting fields at the cervical spine.
      Junction shifts are conventionally used to prevent setup error-induced
      overdosage/underdosage from occurring at the same location. This study compared
      the dosimetric differences at the cranial-spinal junction between a single
      gradient junction technique and conventional multiple-junction shifts and
      evaluated the effect of setup errors on the dose distributions between both
      techniques for a treatment course and single fraction. Conventionally, 2 lateral
      brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm
      junction shifts. We retrospectively replanned 4 CSI patients using a single
      gradient junction between the lateral brain fields and the posterior spine field.
      The fields were extended to allow a minimum 3-cm field overlap. The dose gradient
      at the junction was achieved using dose painting and intensity-modulated
      radiation therapy planning. The effect of positioning setup errors on the dose
      distributions for both techniques was simulated by applying shifts of +/- 3 and
      5mm. The resulting cervical spine doses across the field junction for both
      techniques were calculated and compared. Dose profiles were obtained for both a
      single fraction and entire treatment course to include the effects of the
      conventional weekly junction shifts. Compared with the conventional technique,
      the gradient-dose technique resulted in higher dose uniformity and conformity to
      the target volumes, lower organ at risk (OAR) mean and maximum doses, and
      diminished hot spots from systematic positioning errors over the course of
      treatment. Single-fraction hot and cold spots were improved for the gradient-dose
      technique. The single-gradient junction technique provides improved conformity,
      dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one
      plan for the entire treatment course, which reduces the potential human error
      associated with conventional 4-shifted plans.

PMID- 24913467
TI  - Dosimetric comparison of IMRT rectal and anal canal plans generated using an
      anterior dose avoidance structure.
AB  - To describe a dosimetric method using an anterior dose avoidance structure (ADAS)
      during the treatment planning process for intensity-modulated radiation therapy
      (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients
      were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1
      (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans
      were created: one employing an ADAS (ADAS plan) and the other replanned without
      an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the
      inguinal nodes and primary target providing a single organ at risk that is
      completely outside of the target volume. Each plan used the same beam parameters
      and was analyzed by comparing target coverage, overall plan dose conformity using
      a conformity number (CN) equation, bowel dose-volume histograms, and the number
      of segments, daily treatment duration, and global maximum dose. The ADAS and non
      ADAS plans were equivalent in target coverage, mean global maximum dose, and
      sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean
      difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 +/
      0.03 (p < 0.001). The mean difference in the number of segments was 15.7 +/-
      12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter
      by 2.0 +/- 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to
      be a powerful tool when planning rectal and anal canal IMRT cases with critical
      structures partially contained inside the target volume.

PMID- 24913469
TI  - Predicting dosing advantages of factor VIIa variants with altered tissue factor
      dependent and lipid-dependent activities.
AB  - BACKGROUND: Recombinant factor VIIa (rFVIIa) is an FX-cleaving coagulation enzyme
      licensed for the treatment of bleeding episodes in hemophiliacs with inhibitory
      antibodies. Even though the optimal dosing and comparative dose efficacy of
      rFVIIa remain poorly understood, genetic or chemical modifications of rFVIIa have
      been proposed, with the goal of achieving faster and longer hemostatic action. No
      ongoing trial is currently comparing rFVIIa variants with each other. OBJECTIVES
      AND METHODS: We used mathematical modeling to compare the pharmacokinetics, dose
      response (pharmacodynamics) and dose-effect duration
      (pharmacokinetics/pharmacodynamics) of rFVIIa variants to predict their optimal
      doses. The pharmacodynamic (PD) model of FXa generation by FVIIa in complexes
      with tissue factor (TF) and procoagulant lipids (PLs) was validated against
      published ex vivo and in vitro thrombin generation (TG) experiments. To compare
      variants' safety profiles, the highest non-thrombogenic doses were estimated from
      the clinical evidence reported for the licensed rFVIIa product. RESULTS: The PD
      model correctly described the biphasic TF-dependent and PL-dependent dose
      response observed in TG experiments in vitro. The pharmacokinetic/PD simulations
      agreed with published ex vivo TG data for rFVIIa and the BAY 86-6150 variant, and
      explained the similar efficacies of a single dose of 270 MUg kg(-1) (as reported
      in the literature) and repeated doses of 90 MUg kg(-1) of unmodified rFVIIa. The
      duration of the simulated hemostatic effect after a single optimal dose was
      prolonged for rFVIIa variants with increased TF affinity or extended half-lives,
      but not for those with modulated PL activity. CONCLUSIONS: Some modifications of
      the rFVIIa molecule may not translate into a prolonged hemostatic effect.

PMID- 24913468
TI  - Prevalence of lower extremity peripheral artery disease among adult diabetes
      patients in southwestern Uganda.
AB  - BACKGROUND: Peripheral artery disease (PAD) is a major complication of
      atherosclerosis. PAD can be diagnosed with low-cost diagnostic techniques and is
      associated with significant morbidity and mortality. While the major
      epidemiologic risk factors for PAD have been established in the western world,
      data from resource-poor countries are limited. We performed a cross-sectional
      study to determine the prevalence and correlates of PAD among patients with
      diabetes at Mbarara Referral Hospital in southwestern Uganda. METHODS: We
      consecutively enrolled diabetes patients aged 50 years or greater presenting to
      the outpatient clinic. We collected blood for fasting lipid profile, HIV
      serology, and glycosylated hemoglobin, measured blood pressure and ankle brachial
      index, and administered the Edinburgh Claudication Questionnaire (ECQ). We also
      surveyed patients for other PAD risk factors. We used logistic regression to
      determine correlates of PAD. RESULTS: We enrolled 229 diabetes patients. The
      median age of 60 years (IQR 55-66), and 146 (63.7%) were female. Fifty five
      patients (24%) had PAD (ABI of <= 0.9). Of these, 48 /55 (87.27%) had mild PAD
      (ABI 0.71-0.9) while 7/55 (12.73%) had moderate to severe PAD (ABI < 0.7).
      Amongst those with PAD, 24/55 (43.64%) reported claudication by the ECQ.
      Correlates of PAD included female sex (AOR 2.25, 95% CI 1.06 - 4.77, p = 0.034),
      current high blood pressure (AOR 2.59, 95% CI 1.25-5.33, p = 0.01), and being on
      a sulfonylurea-glibenclamide (AOR 3.47, 95% CI 1.55 - 7.76, p = 0.002).
      CONCLUSION: PAD was common in diabetic patients in southwestern Uganda. Given its
      low cost and ease of measurement, ABI deserves further assessment as a screening
      tool for both PAD and long term cardiovascular risk amongst diabetics in this
      region.

PMID- 24913470
TI  - Endoscopic transnasal shim technique for treatment of patulous Eustachian tube.

PMID- 24913471
TI  - Severe cytokine release syndrome after the first dose of Brentuximab Vedotin in a
      patient with relapsed systemic anaplastic large cell lymphoma (sALCL): a case
      report and review of literature.
AB  - Brentuximab Vedotin is an antibody - drug conjugate targeting CD30. We report a
      case of severe cytokine release syndrome (CRS) after administration of the first
      dose of Brentuximab Vedotin in a 64-yr-old patient with relapsed systemic
      anaplastic large cell lymphoma (sALCL). To our knowledge, this is the first case
      of CRS to Brentuximab Vedotin described in the literature. However, CRS to
      Brentuximab Vedotin might be underestimated, as the drug has not been tested in
      large phase III trials yet. 

PMID- 24913473
TI  - Road safety and simulation conferences: an interdisciplinary network for safer
      roads.
AB  - From 23rd to 25th October 2013 more than 300 researchers attended the 4th
      International Conference on Road Safety and Simulation (RSS 2013) in Rome, Italy,
      hosted by the Inter Universities Research Centre for Road Safety (CRISS) at the
      Department of Engineering of Roma Tre University. The aim of the Conference was
      to create a common interdisciplinary arena for researchers and professionals
      involved in road safety, facilitate the exchange of know-how and progress in the
      last advanced techniques, methods and tools and their applications to safety
      analysis. This special issue highlights some of the research presented at the
      Conference. 

PMID- 24913474
TI  - On the required complexity of vehicle dynamic models for use in simulation-based
      highway design.
AB  - INTRODUCTION: This paper presents the results of a comprehensive project whose
      goal is to identify roadway design practices that maximize the margin of safety
      between the friction supply and friction demand. This study is motivated by the
      concern for increased accident rates on curves with steep downgrades, geometries
      that contain features that interact in all three dimensions - planar curves,
      grade, and superelevation. This complexity makes the prediction of vehicle
      skidding quite difficult, particularly for simple simulation models that have
      historically been used for road geometry design guidance. METHOD: To obtain
      estimates of friction margin, this study considers a range of vehicle models,
      including: a point-mass model used by the American Association of State Highway
      Transportation Officials (AASHTO) design policy, a steady-state "bicycle model"
      formulation that considers only per-axle forces, a transient formulation of the
      bicycle model commonly used in vehicle stability control systems, and finally, a
      full multi-body simulation (CarSim and TruckSim) regularly used in the automotive
      industry for high-fidelity vehicle behavior prediction. The presence of skidding-
      the friction demand exceeding supply--was calculated for each model considering a
      wide range of vehicles and road situations. RESULTS: The results indicate that
      the most complicated vehicle models are generally unnecessary for predicting
      skidding events. However, there are specific maneuvers, namely braking events
      within lane changes and curves, which consistently predict the worst-case
      friction margins across all models. This suggests that any vehicle model used for
      roadway safety analysis should include the effects of combined cornering and
      braking. PRACTICAL IMPLICATIONS: The point-mass model typically used by highway
      design professionals may not be appropriate to predict vehicle behavior on high
      speed curves during braking in low-friction situations. However, engineers can
      use the results of this study to help select the appropriate vehicle dynamic
      model complexity to use in the highway design process.

PMID- 24913475
TI  - Gender differences of young drivers on injury severity outcome of highway
      crashes.
AB  - PROBLEM: Gender differences of young drivers involved in crashes and the
      associated differences in risk factors have not been fully explored in the United
      States (U.S.). Accordingly, this study investigated the topic, where the odds
      ratios (ORs) were used to identify differences in crash involvements between male
      and female young drivers. METHOD: Logistic regression models for injury severity
      of young male drivers and young female drivers were developed. Different driver,
      environmental, vehicle, and road related factors that have affected young female
      drivers' and young male drivers' crash involvements were identified using the
      models. RESULTS: Results indicated that some variables are significantly related
      to female drivers' injury risk but not male drivers' injury risk and vice versa.
      Variables such as driving with valid licenses, driving on weekends, avoidance or
      slow maneuvers at time of crash, non-collision and overturn crashes, and
      collision with a pedestrian were significant variables in female driver injury
      severity model but not in young male driver severity model. Travel on graded
      roadways, concrete surfaces, and wet road surfaces, collision with another
      vehicle, and rear-end collisions were variables that were significant in male
      driver severity model but not in female-driver severity model. SUMMARY: Factors
      which increase young female drivers' injury severity and young male drivers'
      injury severity were identified. This study adds detailed information about
      gender differences and similarities in injury severity risk of young drivers.
      PRACTICAL APPLICATIONS: It is important to note that the findings of this study
      show that gender differences do exists among young drivers. This sends a message
      to the industry that the transportation professionals and researchers, who are
      developing countermeasures to increase the traffic safety, may need to pay
      attention to the differences. This might be particularly true when developing
      education materials for driver training for young/inexperienced drivers.

PMID- 24913476
TI  - Analyzing road design risk factors for run-off-road crashes in The Netherlands
      with crash prediction models.
AB  - PROBLEM: About 50% of all road traffic fatalities and 30% of all traffic injuries
      in the Netherlands take place on rural roads with a speed limit of 80 km/h. About
      50% of these crashes are run-off-road (ROR) crashes. To reduce the number of
      crashes on this road type, attention should be put on improving the safety of the
      infrastructure of this road type. With the development of a crash prediction
      model for ROR crashes on rural roads with a speed limit of 80 km/h, this study
      aims at making a start in providing the necessary new tools for a proactive road
      safety policy to road administrators in the Netherlands. METHOD: The paper
      presents a basic framework of the model development, comprising a problem
      description, the data used, and the method for developing the model. The model is
      developed with the utilization of generalized linear modeling in SAS, using the
      Negative Binomial probability distribution. A stepwise approach is used by adding
      one variable at a time, which forms the basis for striving for a parsimonious
      model and the evaluation of the model. The likelihood ratio test and the Akaike
      information criterion are used to assess the model fit, and parameter estimations
      are compared with literature findings to check for consistency. RESULTS: The
      results comprise two important outcomes. One is a crash prediction model (CPM) to
      estimate the relative safety of rural roads with a speed limit of 80 km/h in a
      network. The other is a small set of estimated effects of traffic volume and road
      characteristics on ROR crash frequencies. PRACTICAL APPLICATIONS: The results may
      lead to adjustments of the road design guidelines in the Netherlands and to
      further research on the quantification of risk factors with crash prediction
      models.

PMID- 24913477
TI  - A comparison of contributing factors between alcohol related single vehicle
      motorcycle and car crashes.
AB  - INTRODUCTION: Alcohol related crashes have accounted for approximately 35% of
      fatal crashes per year since 1994 nationwide, with approximately 30% involving
      impairment over the legal blood alcohol content limit of 0.08%. Educational
      campaigns and law enforcement efforts are two components of multi-faceted
      programs aimed toward reducing impaired driving. It is crucial that further
      research be conducted to guide the implementation of enforcement and educational
      programs. METHOD: This research attempts to provide such guidance by examining
      differences in alcohol-involved crashes involving motorcycles and passenger cars.
      Prior safety research has shown that motorcyclists follow a significantly
      different culture than the average passenger car operator. These cultural
      differences may be reflected by differences in the contributing factors affecting
      crashes and the severity of the resulting injuries sustained by the driver or
      motorcyclist. This research is focused on single-vehicle crashes only, in order
      to isolate modal effects from the contribution of additional vehicles. The crash
      data provided for this study are from the Ohio Department of Public Safety from
      2009 through 2012. RESULTS: The injury severity data are analysed through the
      development of two mixed logit models, one for motorcyclists and one for
      passenger car drivers. The models quantify the effects of various factors,
      including horizontal curves, speeds, seatbelt use, and helmet use, which indicate
      that the required motor skills and balance needed for proper motorcycle operation
      compounded with a lack of mechanical protection make motorcyclists more prone to
      severe injuries, particularly on curves and in collisions with roadside objects.
      PRACTICAL APPLICATIONS: The findings of this study have been incorporated into
      combined motorcycle and sober driving educational safety campaigns. The results
      have shown to be favorable in supporting national campaign messages with local
      justification and backing.

PMID- 24913478
TI  - Divided attention in young drivers under the influence of alcohol.
AB  - INTRODUCTION: The present research evaluates driving impairment linked to divided
      attention task and alcohol and determines whether it is higher for novice drivers
      than for experienced drivers. METHOD: Novice and experienced drivers participated
      in three experimental sessions in which blood alcohol concentrations (BACs) were
      0.0 g/L, 0.2 g/L, and 0.5 g/L. They performed a divided attention task with a
      main task of car-following task and an additional task of number parity
      identification. Driving performance, response time and accuracy on the additional
      task were measured. RESULTS: ANOVA showed a driving impairment and a decrease in
      additional task performance from a BAC of 0.5 g/L, particularly for novice
      drivers. Indeed, the latter adopt more risky behavior such as tailgating. In the
      divided attention task, driving impairment was found for all drivers and
      impairment on information processing accuracy was highlighted, notably in
      peripheral vision. PRACTICAL APPLICATIONS: The divided attention task used here
      provides a relevant method for identifying the effects of alcohol on cognitive
      functions and could be used in psychopharmacological research.

PMID- 24913480
TI  - Assessing the risk of secondary crashes on highways.
AB  - INTRODUCTION: The occurrence of "secondary crashes" is one of the critical yet
      understudied highway safety issues. Induced by the primary crashes, the
      occurrence of secondary crashes does not only increase traffic delays but also
      the risk of inducing additional incidents. Many highway agencies are highly
      interested in the implementation of safety countermeasures to reduce this type of
      crashes. However, due to the limited understanding of the key contributing
      factors, they face a great challenge for determining the most appropriate
      countermeasures. METHOD: To bridge this gap, this study makes important
      contributions to the existing literature of secondary incidents by developing a
      novel methodology to assess the risk of having secondary crashes on highways. The
      proposed methodology consists of two major components, namely: (a) accurate
      identification of secondary crashes and (b) statistically robust assessment of
      causal effects of contributing factors. The first component is concerned with the
      development of an improved identification approach for secondary accidents that
      relies on the rich traffic information obtained from traffic sensors. The second
      component of the proposed methodology is aimed at understanding the key
      mechanisms that are hypothesized to cause secondary crashes through the use of a
      modified logistic regression model that can efficiently deal with relatively rare
      events such as secondary incidents. The feasibility and improved performance of
      using the proposed methodology are tested using real-world crash and traffic flow
      data. RESULTS: The risk of inducing secondary crashes after the occurrence of
      individual primary crashes under different circumstances is studied by employing
      the estimated regression model. Marginal effect of each factor on the risk of
      secondary crashes is also quantified and important contributing factors are
      highlighted and discussed. PRACTICAL APPLICATIONS: Massive sensor data can be
      used to support the identification of secondary crashes. The occurrence mechanism
      of these secondary crashes can be investigate by the proposed model.
      Understanding the mechanism helps deploy appropriate countermeasures to mitigate
      or prevent the secondary crashes.

PMID- 24913479
TI  - Assessing characteristics related to the use of seatbelts and cell phones by
      drivers: application of a bivariate probit model.
AB  - INTRODUCTION: The effects of cell phone use and safety belt use have been an
      important focus of research related to driver safety. Cell phone use has been
      shown to be a significant source of driver distraction contributing to
      substantial degradations in driver performance, while safety belts have been
      demonstrated to play a vital role in mitigating injuries to crash-involved
      occupants. METHOD: This study examines the prevalence of cell phone use and
      safety belt non-use among the driving population through direct observation
      surveys. A bivariate probit model is developed to simultaneously examine the
      factors that affect cell phone and safety belt use among motor vehicle drivers.
      RESULTS: The results show that several factors may influence drivers' decision to
      use cell phones and safety belts, and that these decisions are correlated.
      PRACTICAL APPLICATIONS: Understanding the factors that affect both cell phone use
      and safety belt non-use is essential to targeting policy and programs that reduce
      such behavior.

PMID- 24913481
TI  - Relationships between frequency of driving under the influence of cannabis, self
      reported reckless driving and risk-taking behavior observed in a driving
      simulator.
AB  - INTRODUCTION: The role of cannabis consumption in traffic crashes is unclear and
      the causal link between cannabis and collisions is still to be demonstrated.
      While cannabis use is very likely to impair driving ability, there is as yet no
      overwhelming evidence that cannabis use in isolation contributes more to
      collisions than other characteristics inherent to cannabis users. As noted in a
      growing body of literature, individuals driving under the influence of cannabis
      (DUIC) seem to exhibit a general reckless driving style putting them at higher
      risk to be involved in traffic crashes. METHOD: This study aims at investigating
      the relationship between self-reported DUIC and reckless driving by means of self
      reported measures and direct observations made in a driving simulator.
      Participants (n=72) were required to be between 18 and 25 years of age, to hold a
      valid driver's license, and to drive at least twice a week. They completed
      standard driving simulation tasks recreating everyday on-road trivial conditions.
      RESULTS: Results show that people admitting that they commit more real-life
      dangerous driving behaviors reached higher maximum speed and demonstrated more
      reckless driving behaviors on the driving simulation tasks. Self-reported DUIC is
      associated with a risky driving style including a broad range of reckless on-road
      behaviors and support the problem driving behavior theory. Moreover, beyond
      confounding factors, both self-report DUIC and observed dangerous behaviors are
      associated with real-life traffic violations. PRACTICAL APPLICATIONS: Since DUIC
      appears to be related to an overall reckless style of driving, it is proposed
      that public safety policies should be more holistic, simultaneously targeting
      multiple on-road dangerous behaviors for intervention.

PMID- 24913482
TI  - Impact of texting on young drivers' behavior and safety on urban and rural roads
      through a simulation experiment.
AB  - PROBLEM: This research aims to investigate the impact of texting on the behavior
      and safety of young drivers on urban and rural roads. METHOD: A driving simulator
      experiment was carried out in which 34 young participants drove in different
      driving scenarios; specifically, driving in good weather, in raining conditions,
      in daylight and in night were examined. Lognormal regression methods were used to
      investigate the influence of texting as well as various other parameters on the
      mean speed and mean reaction time. Binary logistic methods were used to
      investigate the influence of texting use as well as various other parameters in
      the probability of an accident. RESULTS: It appears that texting leads to
      statistically significant decrease of the mean speed and increase of the mean
      reaction time in urban and rural road environment. Simultaneously, it leads to an
      increased accident probability due to driver distraction and delayed reaction at
      the moment of the incident. It appeared that drivers using mobile phones with a
      touch screen present different driving behavior with respect to their speed,
      however, they had an even higher probability of being involved in an accident.
      DISCUSSION: The analysis of the distracted driving performance of drivers who are
      texting while driving may allow for the identification of measures for the
      improvement of driving performance (e.g., restrictive measures, training and
      licensing, information campaigns). PRACTICAL APPLICATIONS: The identification of
      some of the parameters that have an impact on the behavior and safety of young
      drivers concerning texting and the consequent results can be exploited by policy
      decision makers in future efforts for the improvement of road safety.

PMID- 24913483
TI  - Post-stroke driving: examining the effect of executive dysfunction.
AB  - INTRODUCTION: Executive dysfunction can refer to both neurocognitive deficits and
      behavioral symptoms that include impaired judgment, slow decision making,
      disorganization, impulsiveness, and risk-taking behaviors. Executive dysfunction
      is relatively common in the post-stroke population but is often undetected. The
      impact of executive dysfunction on post-stroke driving is unclear but it may pose
      a risk to affected drivers and other road users. AIM: The aim of this study was
      to investigate the relationship between executive functioning following stroke
      and driving performance. METHODOLOGY: A case-control study design was used.
      Purposive sampling was used to recruit stroke participants (n=19) and healthy
      controls (n=22). Participants were screened using a battery of psychometric
      assessments including the Montreal Cognitive Assessment and the Benton Judgment
      of Line Orientation. Driving performance was assessed using the STISIM driving
      simulator. Executive function was assessed using the Behavioural Assessment of
      the Dysexecutive Syndrome (BADS) and the Trail Making Test Part B. RESULTS: The
      control participants performed better than the stroke participants on the driving
      assessment and psychometric assessments. There was an association between the
      scores of the Trail Making Test Part B (Rho=0.34, p=0.034) and the Key Search
      Test of the BADS (Rho=-0.61, p=0.005), and the driving assessment scores.
      However, there was no association between the overall BADS scores and the driving
      assessment scores of the stroke participants. CONCLUSIONS: The stroke
      participants underperformed in the driving assessment and the psychometric
      assessments that detected neurocognitive deficits, which included executive
      function. The Trail Making Test Part B and Key Search Test of the BADS were
      related to identify participants' deterioration in driving performance. Practical
      Applications: In clinical practice, the latter could be used as an indication of
      a post-stroke driver's performance.

PMID- 24913484
TI  - The combination of short rest and energy drink consumption as fatigue
      countermeasures during a prolonged drive of professional truck drivers.
AB  - One of the major concerns for professional drivers is fatigue. Many studies
      evaluated specific fatigue countermeasures, in many cases comparing the
      efficiency of each method separately. The present study evaluated the
      effectiveness of rest areas combined with consumption of energy drinks on
      professional truck drivers during a prolonged simulated drive. Fifteen
      professional truck drivers participated in three experimental sessions: control
      drivers were asked to drink 500 ml of a placebo drink prior to the beginning of
      the drive. Energy drink-drivers were asked to drink 500 ml of an energy drink
      containing 160 mg of caffeine prior to the beginning of the drive, and an Energy
      drink+Rest session--where the drivers were asked to drink 500 ml of an energy
      drink prior to driving, and rest for 10 min at a designated rest area zone 100
      min into the drive. For all sessions, driving duration was approximately 150 min
      and consisted of driving on a monotonous, two-way rural road. In addition to
      driving performance measures, subjective measures, and heart rate variability
      were obtained. Results indicated that consumption of an energy drink (in both
      sessions) facilitated lower lane position deviations and reduced steering wheel
      deviations during the first 80-100 min of the drive relative to the control
      sessions. Resting after 100 min of driving, in addition to the energy drink that
      was consumed before the drive, enabled the drivers to maintain these abilities
      throughout the remainder of the driving session. Practical applications:
      Practical applications arising from the results of this research may give
      indication on the possible added value of combining fatigue counter measures
      methods during a prolonged drive and the importance of the timing of the use for
      each method.

PMID- 24913485
TI  - Analysis of driver speeds under night driving conditions using a driving
      simulator.
AB  - PROBLEM: Accident statistics demonstrate that there should be a greater focus on
      nighttime driving to improve our knowledge of driver behavior under poor lighting
      conditions. However, the current geometric design criteria do not take into
      account driving at night. Moreover, studies that propose predictive models of
      operating speed only consider daytime driving conditions. METHOD: This study
      compares driver speed behavior during daytime and nighttime driving and models
      operating speeds and speed differentials, identifying significant factors that
      influence speed behavior under different lighting conditions. The research was
      carried out using a driving simulator for a section of an existing two-lane rural
      road composed of 39 tangent-curve configurations. Speed profiles were recorded
      for 40 drivers under simulated daytime and nighttime driving conditions. RESULTS:
      New predictive speed models, differentiated for daytime and nighttime driving,
      are proposed that highlight the effects of different geometric predictors under
      different visibility conditions. Specifically, predictive models for operating
      speed on curves identified the inverse of the radius and the deflection angle of
      the curve as predictors under both driving conditions. For speed differentials
      based on the 85th percentile for maximum speed reduction (85 MSR), we found that
      the inverse of the approaching tangent length and of the curve radius
      significantly explained the dependent variable in both cases, with a higher
      dependence of nighttime 85 MSR on the curve geometry than on the tangent length.
      Tangent length had a significant effect on operating speed for independent
      tangents only for the daytime model, whereas the inverse of the previous radius
      was confirmed as a predictor for both visibility conditions. PRACTICAL
      APPLICATIONS: This research may influence design considerations for nighttime
      driving by providing evidence of the effects of nighttime conditions on driver
      speed choices and road safety.

PMID- 24913487
TI  - Driving simulator validation of driver behavior with limited safe vantage points
      for data collection in work zones.
AB  - INTRODUCTION: This study is aimed at validating a driving simulator (DS) for the
      study of driver behavior in work zones. A validation study requires field data
      collection. For studies conducted in highway work zones, the availability of safe
      vantage points for data collection at critical locations can be a significant
      challenge. A validation framework is therefore proposed in this paper,
      demonstrated using a fixed-based DS that addresses the issue by using a global
      positioning system (GPS). METHODS: The validation of the DS was conducted using
      objective and subjective evaluations. The objective validation was divided into
      qualitative and quantitative evaluations. The DS was validated by comparing the
      results of simulation with the field data, which were collected using a GPS along
      the highway and video recordings at specific locations in a work zone. The
      constructed work zone scenario in the DS was subjectively evaluated with 46
      participants. RESULTS: The objective evaluation established the absolute and
      relative validity of the DS. The mean speeds from the DS data showed excellent
      agreement with the field data. The subjective evaluation indicated realistic
      driving experience by the participants. PRACTICAL APPLICATIONS: The use of GPS
      showed that continuous data collected along the highway can overcome the
      challenges of unavailability of safe vantage points especially at critical
      locations. Further, a validated DS can be used for examining driver behavior in
      complex situations by replicating realistic scenarios.

PMID- 24913486
TI  - Acute effects of alcohol on inhibitory control and simulated driving in DUI
      offenders.
AB  - INTRODUCTION: The public health costs associated with alcohol-related traffic
      accidents have prompted considerable research aimed at identifying
      characteristics of individuals who drive under the influence (DUI) in order to
      improve treatment and prevention strategies. Survey studies consistently show
      that DUI offenders self-report higher levels of impulsivity compared to their
      nonoffending counterparts. However, little is known about how individuals with a
      DUI history respond under alcohol. Inhibitory control is a behavioral component
      of impulsivity thought to underlie risky drinking and driving behaviors. METHOD:
      The present study examined the degree to which DUI drivers display deficits of
      inhibitory control in response to alcohol and the degree to which alcohol
      impaired their simulated driving performance. It was hypothesized that DUI
      offenders would display an increased sensitivity to the acute impairing effects
      of alcohol on simulated driving performance. Young adult drivers with a history
      of DUI and a demographically-comparable group of drivers with no history of DUI
      (controls) were tested following a 0.65 g/kg dose of alcohol and a placebo.
      Inhibitory control was measured by using a cued go/no-go task. Drivers then
      completed a driving simulation task that yielded multiple indicators of driving
      performance, such as within-lane deviation, steering rate, centerline crossings
      and road edge excursions, and drive speed. RESULTS: Results showed that although
      DUI offenders self-reported greater levels of impulsivity than did controls, no
      group differences were observed in the degree to which alcohol impaired
      inhibitory control and driving performance. The findings point to the need to
      identify other aspects of behavioral dysfunction underlying the self-reported
      impulsivity among DUI offenders, and to better understand the specific driving
      situations that might pose greater risk to DUI offenders. PRACTICAL APPLICATIONS:
      The systematic study of candidate cognitive deficits in DUI offenders will
      provide important information on their role in risky driving behavior and
      decisions to drink and drive. Such information is critical for guiding new
      interventions for DUI offenders that will move treatment beyond general addiction
      counseling.

PMID- 24913488
TI  - Enhancement of road delineation can reduce safety.
AB  - BACKGROUND: New in-vehicle technologies often outpace the scientific support for
      their value. In lieu of valid and consistent scientific support, common wisdom is
      used, as in the assumption that enhanced roadway delineation improves driving
      safety. OBJECTIVE: To evaluate the effects of a Visibility Enhancement System
      that selectively improves lane markers' visibility on driving safety. METHOD: A
      simulation experiment assessed the effects of an in-car lane Visibility
      Enhancement System (VES) that highlights the edges of the road ahead on driver's
      behavior and overall safety, under normal and reduced visibility conditions.
      Thirty drivers drove in a fix-based simulator through a winding rural road, while
      attempting to avoid un-enhanced and unexpected obstacles that appeared on the
      driving lane from time to time. The simulated VES highlighted the road edges up
      to a distance of 90 m with two alternative configurations: two continuous red
      lines or a series of red crosses. The effects of the two VES configurations on
      performance were measured during night and fog driving. Performance measures
      included speed, lane keeping behavior, eye scanning pattern, reaction time (RT)
      and collisions with the un-enhanced unexpected obstacles. Subjective measures
      included confidence and stress. RESULTS: With the VES, drivers were more
      confident, less stressed, and drove faster, but had almost twice as many
      collisions with the unexpected obstacles. Also, steering/braking RT to the
      obstacles was longer with the VES than without it by nearly 44 msec. CONCLUSIONS:
      The results are consistent with Lebowitz's theory (1977). While the VES enhanced
      spatial orientation, it fooled the drivers into assuming that the visibility of
      obstacles on the road was also improved, and thus actually reduced safety.
      PRACTICAL APPLICATIONS: When visibility is an issue in nighttime crashes, the
      site-specific crashes should be investigated, in cases of collision with objects
      on-the-road, improved delineation should be ruled out.

PMID- 24913489
TI  - The effect of different navigation voices on trust and attention while using in
      vehicle navigation systems.
AB  - INTRODUCTION: Automobiles are suffused with computers and technology designed to
      support drivers at all levels of the driving hierarchy. Classic secondary
      devices, such as in-vehicle navigation systems (IVNS), present strategic and
      tactical information to drivers. In order to mitigate the potential distraction
      and workload when interacting with these devices while driving, IVNS often employ
      voices to deliver navigational instructions. In contrast, voices are used during
      interpersonal encounters to engage the listener, provide clues about the
      speaker's personality and make judgments about them, for example, whether to like
      them and to trust them. METHOD: A study conducted within a fixed-based medium
      fidelity driving simulator investigated if drivers made similar 'personality'
      attributions to voices emanating from an IVNS and if this subsequently affected
      how they engaged with the device while driving. Twenty-nine experienced drivers
      and IVNS users drove to a specified destination with a simulated IVNS and
      authentically reproduced UK road signage to support their route-finding. Either
      of two navigation voices were used; one considered 'high-trust' and the other
      'low-trust.' Presented with a conflict scenario, where the verbal route guidance
      differed to the road signs, 22 drivers followed the IVNS instruction rather than
      the road signs. Of these, the majority were using the 'high-trust' voice.
      RESULTS: A post-drive questionnaire revealed that, despite the fact that message
      content and delivery remained equivalent, participants recognized different
      attributes ('personalities') associated with each of the navigation voices. This
      influenced their attitudes towards them, including how much they liked them,
      their preferences for use, and the level of trust that they associated with each
      voice. PRACTICAL APPLICATIONS: While these, so-called, social responses may be
      invited and indeed encouraged in other contexts, in the automotive domain they
      are likely to conflict with the intended benefits of using a voice to deliver
      route guidance and therefore have implications for road safety and design.

PMID- 24913491
TI  - A mathematical model for predicting lane changes using the steering wheel angle.
AB  - INTRODUCTION: Positive safety effects of advanced driver assistance systems can
      only become effective if drivers accept and use these systems. Early detection of
      driver's intention would allow for selective system activation and therefore
      reduce false alarms. METHOD: This driving simulator study aims at exploring early
      predictors of lane changes. In total, 3111 lane changes of 51 participants on a
      simulated highway track were analyzed. RESULTS: Results show that drivers stopped
      their engagement in a secondary task about 7s before crossing the lane, which
      indicates a first planning phase of the maneuver. Subsequently, drivers start
      moving toward the lane, marking a mean steering wheel angle of 2.5 degrees .
      Steering wheel angle as a directly measurable vehicle parameter appears as a
      promising early predictor of a lane change. A mathematical model of the steering
      wheel angle is presented, which is supposed to contribute for predicting lane
      change maneuvers. PRACTICAL APPLICATIONS: The mathematical model will be part of
      a further predictor of lane changes. This predictor can be a new advanced driver
      assistance system able to recognize a driver's intention. With this knowledge,
      other systems can be activated or deactivated so drivers get no annoying and
      exhausting alarm signals. This is one way how we can increase the acceptance of
      assistance systems.

PMID- 24913490
TI  - Driver's behavioral adaptation to adaptive cruise control (ACC): the case of
      speed and time headway.
AB  - PROBLEM: The Adaptive Cruise Control is an Advanced Driver Assistance System
      (ADAS) that allows maintaining given headway and speed, according to settings pre
      defined by the users. Despite the potential benefits associated to the
      utilization of ACC, previous studies warned against negative behavioral
      adaptations that might occur while driving with the system activated.
      Unfortunately, up to now, there are no unanimous results about the effects
      induced by the usage of ACC on speed and time headway to the vehicle in front.
      Also, few studies were performed including actual users of ACC among the
      subjects. OBJECTIVES: This research aimed to investigate the effect of the
      experience gained with ACC on speed and time headway for a group of users of the
      system. In addition, it explored the impact of ACC usage on speed and time
      headway for ACC users and regular drivers. METHOD: A matched sample driving
      simulator study was planned as a two-way (2*2) repeated measures mixed design,
      with the experience with ACC as between-subjects factor and the driving condition
      (with ACC and manually) as within-subjects factor. RESULTS: The results show that
      the usage of ACC brought a small but not significant reduction of speed and,
      especially, the maintenance of safer time headways, being the latter result
      greater for ACC users, probably as a consequence of their experience in using the
      system. SUMMARY: The usage of ACC did not cause any negative behavioral
      adaptations to the system regarding speed and time headway. PRACTICAL
      APPLICATIONS: Based on this research work, the Adaptive Cruise Control showed the
      potential to improve road safety for what concerns the speed and the time headway
      maintained by the drivers. The speed of the surrounding traffic and the minimum
      time headway settable through the ACC seem to have an important effect on the
      road safety improvement achievable with the system.

PMID- 24913492
TI  - The use of meta-analysis or research synthesis to combine driving simulation or
      naturalistic study results on driver distraction.
AB  - Three important and inter-related topics are addressed in this paper. First, the
      importance of meta-analysis and research synthesis methods to combine studies on
      traffic safety, in general, and on driver distraction, in particular, is briefly
      reviewed. Second, naturalistic, epidemiologic, and driving simulation studies on
      driver distraction are used to illustrate convergent and divergent results that
      have accumulated thus far in this domain of research. In particular, mobile phone
      conversation, passenger presence, and text messaging naturalistic studies use
      meta-analyses and research syntheses to illustrate important patterns of results
      that are in need of more in-depth study. Third, a number of driver distraction
      study limitations such as poorly defined dependent variables, lack of
      methodological detail, and omission of statistical information prevent the
      integration of many studies into meta-analyses. In addition, the overall quality
      of road safety studies suffers from these same limitations and suggestions for
      improvement are made to guide researchers and reviewers. Practical Applications.
      The use of research synthesis and meta-analysis provide comprehensive estimates
      of the impact of distractions on driving performance, which can be used to guide
      public policy and future research. 

PMID- 24913493
TI  - The influence of clear zone size and roadside vegetation on driver behavior.
AB  - INTRODUCTION: Roadside vegetation provides numerous environmental and
      psychological benefits to drivers. Previous studies have shown that natural
      landscapes can effectively lower crash rates and cause less frustration and
      stress to the driver. However, run-off-the-road crashes resulting in a collision
      with a tree are twice as likely to result in a fatality, reinforcing the need to
      examine the placement of vegetation within the clear zone. METHOD: This study
      explores the relationship between the size of the clear zone and the presence of
      roadside vegetation on vehicle speed and lateral position. A static evaluation,
      distributed electronically to 100 licensed drivers, was utilized to gather speed
      selections for both real and virtual roads containing four combinations of clear
      zone sizes and roadside vegetation densities. A case study was included in the
      static evaluation to investigate the presence of utility poles near the edge of
      the road on speed selection. Validation of the static evaluation was performed by
      a field data collection on the same roadways shown to participants in the
      evaluation. RESULTS: The speeds observed in the field for roadways with medium
      clear zone/dense vegetation or large clear zone/spare vegetation correlated with
      the speeds chosen by static evaluation participants. Further field data were
      obtained on vehicle speeds and lateral positions for additional roads
      demonstrating the same clear zone size/vegetation density combinations. PRACTICAL
      APPLICATION: This study successfully demonstrates the relationship between clear
      zone design and driver behavior, which could improve clear zone design practices
      and thus roadway safety.

PMID- 24913494
TI  - A hormone-dependent feedback-loop controls androgen receptor levels by limiting
      MID1, a novel translation enhancer and promoter of oncogenic signaling.
AB  - BACKGROUND: High androgen receptor (AR) level in primary tumour predicts
      increased prostate cancer (PCa)-specific mortality. Furthermore, activations of
      the AR, PI3K, mTOR, NFkappaB and Hedgehog (Hh) signaling pathways are involved in
      the fatal development of castration-resistant prostate cancer during androgen
      ablation therapy. MID1, a negative regulator of the tumor-suppressor PP2A, is
      known to promote PI3K, mTOR, NFkappaB and Hh signaling. Here we investigate the
      interaction of MID1 and AR. METHODS: AR and MID1 mRNA and protein levels were
      measured by qPCR, Western blot and immunohistochemistry. Co-immunoprecipitation
      followed by PCR and RNA-pull-down followed by Western blot was used to
      investigate protein-mRNA interaction, chromatin-immunoprecipitation followed by
      next-generation sequencing for identification of AR chromatin binding sites. AR
      transcriptional activity and activity of promoter binding sites for AR were
      analyzed by reporter gene assays. For knockdown or overexpression of proteins of
      interest prostate cancer cells were transfected with siRNA or expression
      plasmids, respectively. RESULTS: The microtubule-associated MID1 protein complex
      associates with AR mRNA via purine-rich trinucleotide repeats, expansions of
      which are known to correlate with ataxia and cancer. The level of MID1 directly
      correlates with the AR protein level in PCa cells. Overexpression of MID1 results
      in a several fold increase in AR protein and activity without major changes in
      mRNA-levels, whereas siRNA-triggered knockdown of MID1 mRNA reduces AR-protein
      levels significantly. Upregulation of AR protein by MID1 occurs via increased
      translation as no major changes in AR protein stability could be observed. AR on
      the other hand, regulates MID1 via several functional AR binding sites in the
      MID1 gene, and, in the presence of androgens, exerts a negative feedback loop on
      MID1 transcription. Thus, androgen withdrawal increases MID1 and concomitantly AR
      protein levels. In line with this, MID1 is significantly over-expressed in PCa in
      a stage-dependent manner. CONCLUSION: Promotion of AR, in addition to enhancement
      of the Akt-, NFkappaB-, and Hh-pathways by sustained MID1-upregulation during
      androgen deprivation therapy provides a powerful proliferative scenario for PCa
      progression into castration resistance. Thus MID1 represents a novel, multi
      faceted player in PCa and a promising target to treat castration resistant
      prostate cancer.

PMID- 24913496
TI  - The effects of nutrition labeling on consumer food choice: a psychological
      experiment and computational model.
AB  - The widespread availability of calorie-dense food is believed to be a
      contributing cause of an epidemic of obesity and associated diseases throughout
      the world. One possible countermeasure is to empower consumers to make healthier
      food choices with useful nutrition labeling. An important part of this endeavor
      is to determine the usability of existing and proposed labeling schemes. Here, we
      report an experiment on how four different labeling schemes affect the speed and
      nutritional value of food choices. We then apply decision field theory, a leading
      computational model of human decision making, to simulate the experimental
      results. The psychology experiment shows that quantitative, single-attribute
      labeling schemes have greater usability than multiattribute and binary ones, and
      that they remain effective under moderate time pressure. The computational model
      simulates these psychological results and provides explanatory insights into
      them. This work shows how experimental psychology and computational modeling can
      contribute to the evaluation and improvement of nutrition-labeling schemes. 

PMID- 24913495
TI  - 17beta-estradiol increases liver and serum docosahexaenoic acid in mice fed
      varying levels of alpha-linolenic acid.
AB  - Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain
      function, and 17beta-estradiol (E2) appears to increase the conversion of alpha
      linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the
      positive effect of E2 on DHA synthesis is not known. Therefore, the objective of
      this study was to investigate the effects of E2 supplementation on tissue and
      serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 %
      fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 %
      ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks
      of age and half the mice had the pellet removed at 7 weeks of age. Mice were then
      randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration
      was measured in serum, liver and brain. A significant main effect of E2 was found
      for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO
      and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats,
      respectively, compared to unsupplemented mice. There was no effect of E2 on brain
      DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA
      investigated presently, suggesting that higher ALA intake may result in higher
      DHA in individuals with higher E2 status. 

PMID- 24913497
TI  - Secretory phospholipase A2-IIa upregulates HER/HER2-elicited signaling in lung
      cancer cells.
AB  - Lung cancer is the leading cause of cancer death worldwide. There is an urgent
      need for early diagnostic tools and novel therapies in order to increase lung
      cancer survival. Secretory phospholipase A2 group IIa (sPLA2-IIa) is involved in
      inflammation, tumorigenesis and metastasis. We were the first to uncover that
      cancer cells secrete sPLA2-IIa. sPLA2-IIa is overexpressed in almost all
      specimens of human lung cancers examined and is significantly elevated in the
      plasma of lung cancer patients. High levels of plasma sPLA2-IIa are significantly
      associated with advanced stage and decreased overall cancer survival. In this
      study, we further showed that elevated HER/HER2-PI3K-Akt-NF-kappaB signaling
      contributes to sPLA2-IIa overexpression in lung cancer cells. sPLA2-IIa in turn
      phosphorylates and activates HER2 and HER3 in a time- and dose-dependent manner
      in lung cancer cells. The structure and sequence-based docking analysis revealed
      that sPLA2-IIa beta hairpin shares structural similarity with the corresponding
      EGF hairpin. sPLA2-IIa forms an extensive interface with EGFR and brings the two
      lobes of EGFR into an active conformation. sPLA2-IIa also enhances the NF-kappaB
      promoter activity. Anti-sPLA2-IIa antibody, but not the small molecule sPLA2-IIa
      inhibitor LY315920, significantly inhibits sPLA2-IIa-induced activation of NF
      kappaB promoter. Our findings support the notion that sPLA2-IIa functions as a
      ligand for the EGFR family of receptors leading to an elevated HER/HER2-elicited
      signaling. Plasma sPLA2-IIa can potentially serve as lung cancer biomarker and
      sPLA2-IIa is a potential therapeutic target against lung cancer.

PMID- 24913498
TI  - Recurrent and partially reversible cardiomyopathy occurring during treatment with
      bendamustine and rituximab.

PMID- 24913500
TI  - Ruxolitinib and DNA methyltransferase-inhibitors: a foray into combination
      regimens in myelofibrosis.

PMID- 24913499
TI  - Sirolimus, tacrolimus and low-dose methotrexate based graft-versus-host disease
      prophylaxis after non-ablative or reduced intensity conditioning in related and
      unrelated donor allogeneic hematopoietic cell transplant.
AB  - Encouraging results have been reported with sirolimus, tacrolimus and low-dose
      methotrexate after non-myeloablative allogeneic hematopoietic cell transplant. We
      conducted a retrospective analysis of 71 patients with lymphoid malignancies
      treated with this prophylaxis regimen after non-myeloablative or reduced
      intensity allogeneic hematopoietic cell transplant. Grafts were human leukocyte
      antigen (HLA)-matched related in 29 (41%), matched unrelated in 36 (51%) and 9/10
      HLA-matched unrelated in six (8%) patients. The regimen was well tolerated and
      over 90% of patients completed the planned treatment. The cumulative incidences
      of 1-year grade B-D and C-D acute graft-versus-host disease (GVHD) were 0.28 (95%
      confidence interval [CI], 0.18-0.39) and 0.07 (95% CI, 0.03-0.15), respectively,
      and of 1- and 2-year chronic GVHD (National Institutes of Health criteria) in 70
      evaluable patients were 0.15 (95% CI, 0.08-0.24) and 0.33 (95% CI, 0.22-0.44),
      respectively. The median day of onset of acute GVHD was 123 days (range, 17-268
      days). Peri-transplant rituximab or anti-thymocyte globulin did not affect GVHD.
      The cumulative incidence of 1-year non-relapse mortality and relapse were 4% and
      20%, respectively. With a median follow-up of 3.5 (range: 0.18-5.1) years,
      overall survival and progression-free survival at 2 years were 82% and 66%,
      respectively. This GVHD regimen results in a low incidence and severity of acute
      and chronic GVHD after reduced intensity and non-myeloablative allogeneic
      hematopoietic cell transplant for lymphoid malignancies. The study also
      highlights the incidence of late onset acute GVHD in non-myeloablative/reduced
      intensity conditioning, and the contribution of the new GVHD staging system that
      more accurately reflects clinical outcomes. 

PMID- 24913501
TI  - A home-care, early discharge model after autografting in multiple myeloma:
      results of a three-arm prospective, non-randomized study.

PMID- 24913502
TI  - Intrathecal methotrexate prophylaxis and central nervous system relapse in
      patients with diffuse large B-cell lymphoma following rituximab plus
      cyclophosphamide, doxorubicin, vincristine and prednisone.
AB  - This study evaluated the efficacy of central nervous system (CNS) prophylaxis
      using intrathecal methotrexate (IT-MTX) in patients with diffuse large B-cell
      lymphoma (DLBCL). We retrospectively studied 322 patients who achieved first
      complete remission (CR) after rituximab plus cyclophosphamide, doxorubicin,
      vincristine, and prednisone (R-CHOP) therapy. The CNS prophylaxis consisted of
      four doses of IT-MTX (15 mg) with hydrocortisone (25 mg) administered after CR
      was achieved. Forty patients (12%) received CNS prophylaxis (group A) and 282
      patients (88%) did not (group B). Three patients in group A (8%) and eight in
      group B (3%) experienced isolated CNS relapse during the first CR, although this
      difference was not statistically significant (p = 0.14). Ten of 11 CNS relapses
      occurred in the brain parenchyma with (n = 3) or without (n = 7) leptomeningeal
      involvement, and the remaining patient had exclusive leptomeningeal involvement.
      In patients with DLBCL attaining CR after R-CHOP, IT-MTX administration was
      insufficient to prevent CNS relapse. 

PMID- 24913503
TI  - Modulation of lymphocyte subpopulations by extracorporeal photopheresis in
      patients with acute graft-versus-host disease or graft rejection.
AB  - Extracorporeal photopheresis (ECP) constitutes a promising treatment for patients
      with steroid-refractory acute graft-versus-host disease (aGvHD) after allogeneic
      stem cell transplantation and for patients with graft rejection after solid organ
      transplantation (SOT). There is an increasing body of evidence that modulation of
      lymphocyte subsets might play a crucial role in the mechanism of action in ECP.
      We therefore analyzed immunological effects concomitantly with clinical findings
      in patients under ECP therapy using multicolor flow cytometry. In a patient with
      steroid-refractory aGvHD and a patient with progressive bronchiolitis obliterans
      syndrome (BOS) after double-lung transplantation, clinical responses to ECP
      therapy were paralleled by an increase of CD4 + CD25hiFoxP3 + regulatory T cells
      and a decrease of T(EMRA) (CD3 + CD8+ CD45RA+ CD62L+ effector memory T) cells as
      well as of natural killer (NK)T cells. In summary, immunomonitoring of T cell
      subsets can elucidate the mechanism of action in ECP. 

PMID- 24913505
TI  - Splenectomy and second malignancies in patients with Hodgkin lymphoma: is there a
      causal relationship?

PMID- 24913504
TI  - A gene expression based predictor for high risk myeloma treated with intensive
      therapy and autologous stem cell rescue.
AB  - Myeloma is characterized by a highly variable clinical outcome. Despite the
      effectiveness of high-dose therapy, 15% of patients relapse within 1 year. We
      show that these cases also have a significantly shorter post-relapse survival
      compared to the others (median 14.9 months vs. 40 months, p = 8.03 * 10(- 14)).
      There are no effective approaches to define this potentially distinct biological
      group such that treatment could be altered. In this work a series of uniformly
      treated patients with myeloma were used to develop a gene expression profiling
      (GEP)-based signature to identify this high risk clinical behavior. Gene
      enrichment analyses applied to the top differentially expressed genes showed a
      significant enrichment of epigenetic regulators as well as "stem cell" myeloma
      genes. A derived 17-gene signature effectively identifies patients at high risk
      of early relapse as well as impaired overall survival. Integrative genomic
      analyses showed that epigenetic mechanisms may play an important role on
      transcription of these genes. 

PMID- 24913507
TI  - Allogeneic transplant following brentuximab vedotin in patients with relapsed or
      refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma.
AB  - Brentuximab vedotin is an antibody drug conjugate that induces durable objective
      responses in patients with relapsed or refractory Hodgkin lymphoma and systemic
      anaplastic large cell lymphoma. Fifteen of 160 patients who participated in two
      pivotal phase 2 studies received a consolidative allogeneic stem cell transplant
      (allo-SCT) following brentuximab vedotin treatment. This case series describes
      their experience. The studies were approved by Institutional Review Boards prior
      to patient enrollment. Patients received 1.8 mg/kg brentuximab vedotin every 3
      weeks for up to 16 cycles. The estimated 2-year progression-free survival (PFS)
      rate was 66%, and the median PFS has not yet been reached. Eleven of the 15
      patients were alive and the estimated 2-year survival rate was 80%. The safety of
      brentuximab vedotin treatment in this series was consistent with the known safety
      profile in this setting. Brentuximab vedotin is a compelling option for reducing
      tumor burden to facilitate a consolidative allo-SCT. 

PMID- 24913506
TI  - Neoplastic plasma cell aberrant antigen expression patterns and their association
      with genetic abnormalities.
AB  - Little is known about aberrant antigen expression patterns and their association
      with cytogenetic aberrations in multiple myeloma (MM). We examined the
      correlation between flow cytometry and florescence in situ hybridization (FISH)
      in 167 marrow specimens with MM. Gene expression profiling of CD56, CD117, CD52
      and CD20 mRNA in plasma cells (PCs) from patients treated on Total Therapy 2 and
      Total Therapy 3 trials were also evaluated. Higher expression of CD56 and CD117
      was associated with hyperdiploidy. High CD52 mRNA expression was associated with
      c-MAF and FGFR3 subgroups. Higher expression of CD56 mRNA, but lower Kit
      expression, were noted in association with FGFR3. In contrast, the c-MAF subgroup
      showed high Kit expression but lacked NCAM mRNA expression. CKS1B amplification
      showed positive correlation with CD52 (p=0.0065) but negative correlation with
      CD20 (p=0.0207). These findings indicate that phenotypic differences in MM are
      associated with distinct genetic subgroups, which potentially has important
      diagnostic and prognostic value.

PMID- 24913508
TI  - Limited stage diffuse large B-cell lymphoma: comparative effectiveness of
      treatment strategies in a large cohort of elderly patients.
AB  - Optimal treatment for limited stage diffuse large B-cell lymphoma (DLBCL) in the
      elderly is controversial. Using the Surveillance, Epidemiology and End Results
      Medicare database, we compared overall survival (OS), time to second-line therapy
      (surrogate for recurrence) and adverse events in elderly patients diagnosed with
      stage I or II DLBCL in 1999-2009, who received either abbreviated rituximab,
      cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) plus radiation
      or 6-8 cycles of RCHOP alone. Of 874 patients, 359 received abbreviated RCHOP
      with radiation, and 515 received a full course of RCHOP. In propensity score
      adjusted analyses, OS was similar in both groups (hazard ratio [HR] 1.02, 95%
      confidence interval [CI] 0.76, 1.38). Abbreviated RCHOP with radiation was
      associated with lower risk of second-line therapy (HR 0.71, 95% CI 0.53, 0.94)
      and lower odds of febrile neutropenia (odds ratio [OR] 0.27, 95% CI 0.15, 0.50).
      While the two treatments resulted in similar survival, our data suggest that
      abbreviated RCHOP with radiation may be better tolerated than a full course of
      RCHOP. 

PMID- 24913509
TI  - Allogeneic stem cell transplant in patients with chronic lymphocytic leukemia
      with 17p deletion: consult-transplant versus consult- no-transplant analysis.
AB  - Allogeneic stem cell transplant (alloSCT) can overcome the adverse prognosis of
      chronic lymphocytic leukemia with 17p deletion (17p- CLL). However, its
      applicability remains unclear. Since 2007, our leukemia service has referred
      patients with 17p- CLL for alloSCT at presentation. In this study, the outcomes
      of these patients were reviewed retrospectively to determine whether they
      underwent alloSCT and why patients did not undergo alloSCT. Fifty-two patients
      with 17p- CLL who were referred to the transplant service from 2007 to 2010 were
      identified. Of these patients, 32 (62%) did not undergo alloSCT, mainly because
      of treatment- or disease-related complications (n = 15). The 2-year post-referral
      overall survival rates of the alloSCT and non-SCT groups were 64% and 25%,
      respectively (p = 0.001). These findings suggest that while alloSCT is an
      effective therapy in patients with 17p- CLL, pre-SCT complications may preclude a
      significant proportion of patients from undergoing the procedure. 

PMID- 24913510
TI  - Outcome of graft failure after allogeneic stem cell transplant: study of 89
      patients.
AB  - Strategies for reversing graft failure (GF) after allogeneic stem cell transplant
      (SCT) depend on the options available in each situation. GF was reported in 16
      Spanish institutions from January 2006 to July 2011. Primary GF was defined as an
      absolute neutrophil count (ANC) > 0.5 * 10(9)/L not reached by day + 28 after SCT
      from peripheral blood (PB) or bone marrow (BM) progenitors and by day + 42 after
      SCT from unrelated cord blood (UCB) progenitors. Secondary GF was defined as a
      recurrent ANC < 0.5 * 10(9)/L. Eighty-nine patients with GF were reported, and 80
      patients received a second SCT. The 5-year survival probability was 31% (95%
      confidence interval [CI]: 18-44%), and the incidences of non-relapse mortality
      and relapse estimated by competing risks were 47% (95% CI: 36-58%) and 21% (95%
      CI: 4-28%). The strategy adopted to treat GF was heterogeneous, and no approach
      could be unequivocally recommended for this situation. The prognosis of patients
      with GF was poor even after successful recovery from GF. 

PMID- 24913511
TI  - Prognostic impact of beta2-microglobulin in patients with non-gastric mucosa
      associated lymphoid tissue lymphoma.
AB  - Although serum beta2-microglobulin (B2M) has been suggested as a prognostic
      factor for several hematologic malignancies, it has not been comprehensively
      investigated in non-gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
      Between January 2000 and May 2013, a total of 174 patients with non-gastric MALT
      lymphoma were identified from a prospectively developed database. Baseline serum
      B2M was elevated in 17 (10%) patients. In univariate analysis, serum B2M >= 2.5
      mg/L was significantly associated with progression-free survival (PFS, p < 0.001)
      and overall survival (OS, p < 0.001). Multivariate analysis identified serum B2M
      as an independent prognostic factor in PFS (hazard ratio [HR] = 3.5, 95%
      confidence interval [CI]: 1.2-10.0; p = 0.02) and OS (HR = 26.9, 95% CI: 2.7
      269.7; p = 0.005), after adjustment for IPI and treatment modalities. Baseline
      serum B2M is an independent prognostic factor in patients with non-gastric MALT
      lymphoma.

PMID- 24913513
TI  - Digestibility and structural properties of thermal and high hydrostatic pressure
      treated sweet potato (Ipomoea batatas L.) protein.
AB  - This study assessed the effects of thermal (40, 60, 80, 100 and 127  degrees C)
      and high hydrostatic pressure (HHP, 200, 400 and 600 MPa) treatments on the in
      vitro digestibility and structural properties of sweet potato protein (SPP). The
      results showed that the in vitro digestibility of SPP increased significantly
      with increasing heating temperature and heating time (0-60 min), while HHP
      treatment had little or no effect. Native SPP denaturation temperature (T d ) and
      enthalpy change (DeltaH) were 89.0  degrees C and 9.6 J/g, respectively. Thermal
      and HHP treated SPP had T d of 84.6-88.9  degrees C and 86.4-87.6  degrees C,
      respectively. DeltaH of thermal treated SPP was 3.6-6.4 J/g, while that of HHP
      treated SPP was 5.9-7.8 J/g. The differential scanning calorimetry (DSC) results
      demonstrated that HHP and thermal treatments both significantly reduced SPP
      thermodynamic stability. Circular dichroism analyses revealed that native SPP
      contains alpha-helixes, beta-sheets and random coils (4.3, 48.0 and 47.7%,
      respectively). After thermal treatment at 127  degrees C for 20 min, the content
      of alpha-helixes and turns increased significantly (13.2 and 27.6%,
      respectively), whereas the content of beta-sheets decreased significantly
      (12.3%). In contrast, HHP treatment increased the content of beta-sheets, but
      decreased the content of random coils. This study suggested that the SPP
      structure changes might be the main reason affecting the in vitro digestibility
      of SPP, and thermal treatment was more effective at changing SPP secondary
      structures and improving in vitro SPP digestibility than HHP treatment.

PMID- 24913512
TI  - A single-institution analysis of the utility of pre-induction ejection fraction
      measurement in patients newly diagnosed with acute myeloid leukemia.
AB  - Anthracyclines, a standard component of induction therapy for acute myeloid
      leukemia (AML) are known to be cardiotoxic. Existing evidence supporting routine
      baseline pre-induction cardiac function testing is limited. We conducted a
      retrospective analysis of 119 consecutive patients diagnosed with AML at our
      center from 2009 to 2012. In the 76 patients for whom induction chemotherapy was
      planned, baseline ejection fraction measurements were rarely abnormal (four
      cases), and in none of these abnormal cases did the result change management
      decisions. Awaiting LVEF evaluation results led to a delay in chemotherapy
      administration by a mean of approximately 2 days at significant additional costs
      to the healthcare system. Routine baseline ejection fraction measurement should
      be abandoned as it does not change management, results in treatment delay and
      unnecessary healthcare expenditures. More selective baseline testing,
      preferentially in patients in whom there is a clinical reason of cardiac disease,
      should be pursued.

PMID- 24913515
TI  - Evaluation of clinicopathological characteristics and oestrogen receptor gene
      expression in oestrogen receptor-negative, progesterone receptor-positive canine
      mammary carcinomas.
AB  - The existence of the oestrogen receptor-negative (OR(-))/progesterone receptor
      positive (PR(+)) phenotype in canine mammary carcinomas (CMCs) is not well
      understood, although this phenotype was reported consistently in previous
      studies. In the present study, immunohistochemistry (IHC) was performed to
      categorize CMCs with the OR(-)/PR(+) phenotype and compare their
      clinicopathological features with OR(+)/PR(+) tumours. Of a total of 305 CMCs, 36
      (11.8%) were categorized as OR(-)/PR(+) and showed intermediate characteristics
      between those of OR(+)/PR(+) and OR(-)/PR(-) cases. OR mRNA levels were measured
      in formalin-fixed, paraffin wax-embedded samples using a novel branched-chain DNA
      assay method. Similar to the IHC result, one-way analysis of variance showed that
      the mean normalized OR mRNA level of OR(-)/PR(+) tumours (11.4 +/- 16.34) was
      between that of the OR(-)/PR(-) (mean 4.7 +/- 6.35) and OR(+)/PR(+) (mean 15.8 +/
      11.95) (P = 0.033) tumours. Only three of the 36 OR(-)/PR(+) tumours completely
      lacked OR mRNA expression. The OR(-)/PR(+) tumours were not categorized as an
      independent group nor were they included in the other groups on post-hoc
      analysis. OR(-)/PR(+) tumours were associated with factors related to poor
      prognosis compared with OR(+)/PR(+) tumours, but OR(-)/PR(-) tumours were
      associated with the worst prognostic indicators. Further studies are required in
      order to determine the clinical significance of the OR(-)/PR(+) phenotype.

PMID- 24913514
TI  - AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation
      and insulin sensitivity in mice.
AB  - AIMS/HYPOTHESIS: Obesity is characterised by lipid accumulation in skeletal
      muscle, which increases the risk of developing insulin resistance and type 2
      diabetes. AMP-activated protein kinase (AMPK) is a sensor of cellular energy
      status and is activated in skeletal muscle by exercise, hormones (leptin,
      adiponectin, IL-6) and pharmacological agents (5-amino-4-imidazolecarboxamide
      ribonucleoside [AICAR] and metformin). Phosphorylation of acetyl-CoA carboxylase
      2 (ACC2) at S221 (S212 in mice) by AMPK reduces ACC activity and malonyl-CoA
      content but the importance of the AMPK-ACC2-malonyl-CoA pathway in controlling
      fatty acid metabolism and insulin sensitivity is not understood; therefore, we
      characterised Acc2 S212A knock-in (ACC2 KI) mice. METHODS: Whole-body and
      skeletal muscle fatty acid oxidation and insulin sensitivity were assessed in
      ACC2 KI mice and wild-type littermates. RESULTS: ACC2 KI mice were resistant to
      increases in skeletal muscle fatty acid oxidation elicited by AICAR. These mice
      had normal adiposity and liver lipids but elevated contents of triacylglycerol
      and ceramide in skeletal muscle, which were associated with hyperinsulinaemia,
      glucose intolerance and skeletal muscle insulin resistance.
      CONCLUSIONS/INTERPRETATION: These findings indicate that the phosphorylation of
      ACC2 S212 is required for the maintenance of skeletal muscle lipid and glucose
      homeostasis.

PMID- 24913516
TI  - Quality by design: a systematic and rapid liquid chromatography and mass
      spectrometry method for eprosartan mesylate and its related impurities using a
      superficially porous particle column.
AB  - The present work describes the systematic development of a robust, precise, and
      rapid reversed-phase liquid chromatography method for the simultaneous
      determination of eprosartan mesylate and its six impurities using quality-by
      design principles. The method was developed in two phases, screening and
      optimization. During the screening phase, the most suitable stationary phase,
      organic modifier, and pH were identified. The optimization was performed for
      secondary influential parameters--column temperature, gradient time, and flow
      rate using eight experiments--to examine multifactorial effects of parameters on
      the critical resolution and generated design space representing the robust
      region. A verification experiment was performed within the working design space
      and the model was found to be accurate. This study also describes other operating
      features of the column packed with superficially porous particles that allow very
      fast separations at pressures available in most liquid chromatography
      instruments. Successful chromatographic separation was achieved in less than 7
      min using a fused-core C18 (100 mm * 2.1 mm, 2.6 MUm) column with linear gradient
      elution of 10 mM ammonium formate (pH 3.0) and acetonitrile as the mobile phase.
      The method was validated for specificity, linearity, accuracy, precision, and
      robustness in compliance with the International Conference on Harmonization Q2
      (R1) guidelines. The impurities were identified by liquid chromatography with
      mass spectrometry.

PMID- 24913518
TI  - Diabetes: Progress in reducing vascular complications of diabetes.

PMID- 24913519
TI  - Diabetes: Absence of hormone-sensitive lipase associated with risk of T2DM.

PMID- 24913517
TI  - Malformation syndromes associated with disorders of sex development.
AB  - When embryological development of the internal and/or external genitalia is
      disrupted, the patient presents with a disorder of sex development (DSD) in the
      neonatal period or sometime later in life. Some of these patients have other,
      nongenital malformations, which makes their overall management more complex than
      if they just had a DSD. This Review summarises these malformation syndromes and
      discusses the recent research into their aetiology. The genetic causes of these
      malformation syndromes, when they are known, will also be described. Many
      specific genetic mutations are now known in malformation syndromes with a defect
      in hormonal function. By contrast, the genetic causes remain unknown in many
      nonhormonal morphological anomalies that affect the genitalia. 

PMID- 24913520
TI  - Reproductive endocrinology: A microRNA prevents cervical embryonic implantation.

PMID- 24913521
TI  - Genetics: Pinpointing a hotspot in adrenal Cushing syndrome.

PMID- 24913522
TI  - Quantitative assessment of the relationship between cellular morphodynamics and
      signaling events by stochastic analysis of fluorescent images.
AB  - Cell motility involves a number of strategies that cells use in order to seek
      nutrients, escape danger, and fulfill morphogenetic roles. Here we present a
      methodology to quantify morphological changes and their relationship with
      signaling events from time-lapse imaging microscopy experiments, in order to
      characterize physiological and pathological processes. To this aim, the
      stationary spatial pattern of signaling events is determined through an
      intracellular fluorescent probe, and it is related with the frequency and entity
      of morphodynamic events, which are in turn quantified through a stochastic
      approach: two pseudoimages are obtained from a time series of moving cells that
      describe the probability that a pixel belongs to the cell, and the probability
      that a pixel is subject to a dynamic event. The simultaneous construction of
      these maps permits visualization of hot spots of dynamic events, i.e., zones of
      formation of membrane protrusions and retractions and their relationship with the
      signaling events reported by the specific probe employed. The method is tested on
      spontaneous movement of cells, trasfected with redox-sensitive yellow fluorescent
      protein, in which the distribution of the hot spots and its change upon
      expression of constitutively active Rac (V12-Rac), is related to the distribution
      of oxidized spots. 

PMID- 24913523
TI  - Health actions prompted by health assessments for people with intellectual
      disability exceed actions recorded in general practitioners' records.
AB  - People with intellectual disability experience inadequate health care and have
      unmet health needs that can go unidentified or be poorly managed. Health
      assessments have been shown to significantly increase short-term clinical
      activity for people with intellectual disability. The aim of this study was to
      more accurately quantify the effect of health assessments for people with
      intellectual disability by comparing health actions recorded in health assessment
      booklets to actions recorded in general practitioners' (GPs) records in the 12
      month period following the health assessment. Participants were people with
      intellectual disability who had received a Comprehensive Health Assessment
      Program (CHAP), living in the community. The CHAP is a health assessment that is
      demonstrated to significantly increase health actions, compared with usual care,
      for people with intellectual disability. Data collected from three randomised
      controlled trials conducted in South-East Queensland, Australia, from 2000 to
      2010 were pooled and analysed. The health assessment booklet contained
      significantly more information on health actions than GPs' records. Notably,
      hearing tests (risk ratio (RR) = 5.9; 95% confidence interval (CI) = 4.7-7.4),
      breast checks (RR = 3.9; 95% CI = 2.7-5.7), and skin examinations (RR = 7.9; 95%
      CI = 5.9-10.7) were more likely to be recorded in the CHAP booklet. Health
      assessments increase health actions for people with intellectual disability to a
      significantly greater extent than previously demonstrated.

PMID- 24913524
TI  - The reporting quality of randomized controlled trials in orthodontics.
AB  - OBJECTIVES: Accurate trial reporting facilitates evaluation and better use of
      study results. The objective of this article is to investigate the quality of
      reporting of randomized controlled trials (RCTs) in leading orthodontic journals,
      and to explore potential predictors of improved reporting. METHODS: The 50 most
      recent issues of 4 leading orthodontic journals until November 2013 were
      electronically searched. Reporting quality assessment was conducted using the
      modified CONSORT statement checklist. The relationship between potential
      predictors and the modified CONSORT score was assessed using linear regression
      modeling. RESULTS: 128 RCTs were identified with a mean modified CONSORT score of
      68.97% (SD = 11.09). The Journal of Orthodontics (JO) ranked first in terms of
      completeness of reporting (modified CONSORT score 76.21%, SD = 10.1), followed by
      American Journal of Orthodontics and Dentofacial Orthopedics (AJODO) (73.05%, SD
      = 10.1). Journal of publication (AJODO: beta = 10.08, 95% CI: 5.78, 14.38; JO:
      beta = 16.82, 95% CI: 11.70, 21.94; EJO: beta = 7.21, 95% CI: 2.69, 11.72
      compared to Angle), year of publication (beta = 0.98, 95% CI: 0.28, 1.67 for each
      additional year), region of authorship (Europe: beta = 5.19, 95% CI: 1.30, 9.09
      compared to Asia/other), statistical significance (significant: beta = 3.10, 95%
      CI: 0.11, 6.10 compared to non-significant) and methodologist involvement
      (involvement: beta = 5.60, 95% CI: 1.66, 9.54 compared to non-involvement) were
      all significant predictors of improved modified CONSORT scores in the
      multivariable model. Additionally, median overall Jadad score was 2 (IQR = 2)
      across journals, with JO (median = 3, IQR = 1) and AJODO (median = 3, IQR = 2)
      presenting the highest score values. CONCLUSION: The reporting quality of RCTs
      published in leading orthodontic journals is considered suboptimal in various
      CONSORT areas. This may have a bearing in trial result interpretation and use in
      clinical decision making and evidence- based orthodontic treatment interventions.

PMID- 24913525
TI  - Periodontal treatment may reduce levels of systemic inflammation markers
      associated with atherosclerotic profile.

PMID- 24913526
TI  - Low intake of sugars may reduce risk of dental caries.

PMID- 24913527
TI  - Patients with poor oral health status received little dental care and patients at
      the terminal stage of their lives received comprehensive dental treatment.

PMID- 24913528
TI  - Periodontal therapy is associated with decreased risk of developing end-stage
      renal disease--a study using the Taiwan National Health Insurance Database.

PMID- 24913529
TI  - One (small) step closer to public health service in the dental office.

PMID- 24913530
TI  - Self-reported measures may be useful in surveillance for periodontitis.

PMID- 24913531
TI  - Treatment of chronic periodontitis may be improved by the adjunctive use of
      systemic metronidazole.

PMID- 24913533
TI  - Smoking cessation may positively improve clinical periodontal parameters.

PMID- 24913532
TI  - Understanding the effects of periodontal therapy plus azithromycin on glycemic
      control in patients with diabetes remains elusive.

PMID- 24913534
TI  - Individuals with chronic obstructive pulmonary disease (COPD) may be more likely
      to have more severe periodontal disease than individuals without COPD.

PMID- 24913535
TI  - BMI is a predictor of periodontal therapy outcomes.

PMID- 24913536
TI  - Child temperament is as strongly associated with early childhood caries (ECC) as
      poor feeding practices: positive temperament appears protective, negative
      temperament may increase ECC risk.

PMID- 24913537
TI  - Impacted third molars increase the risk for caries and periodontal pathology in
      neighboring second molars.

PMID- 24913538
TI  - Providing dental care coverage to uninsured older US adults who do not use dental
      care may not result in usage rates similar to those with prior coverage and use.

PMID- 24913539
TI  - Dental caries is associated with central and peripheral, but not general,
      adiposity in children.

PMID- 24913540
TI  - Letter to the editor.

PMID- 24913541
TI  - Letter to the editor.

PMID- 24913542
TI  - The jamming elasticity of emulsions stabilized by ionic surfactants.
AB  - Oil-in-water emulsions composed of colloidal-scale droplets are often stabilized
      using ionic surfactants that provide a repulsive interaction between neighboring
      droplet interfaces, thereby inhibiting coalescence. If the droplet volume
      fraction is raised rapidly by applying an osmotic pressure, the droplets remain
      disordered, undergo an ergodic-nonergodic transition, and jam. If the applied
      osmotic pressure approaches the Laplace pressure of the droplets, then the jammed
      droplets also deform. Because solid friction and entanglements cannot play a
      role, as they might with solid particulate or microgel dispersions, the shear
      mechanical response of monodisperse emulsions can provide critical insight into
      the interplay of entropic, electrostatic, and interfacial forces. Here, we
      introduce a model that can be used to predict the plateau storage modulus and
      yield stress of a uniform charge-stabilized emulsion accurately if the droplet
      radius, interfacial tension, surface potential, Debye screening length, and
      droplet volume fraction are known. 

PMID- 24913543
TI  - Striving for good nursing care: nurses' experiences of do not resuscitate orders
      within oncology and hematology care.
AB  - BACKGROUND: Within oncology and hematology care, patients are sometimes
      considered to have such a poor prognosis that they can receive a do not
      resuscitate order from the physician responsible, stipulating that neither basic
      nor advanced coronary pulmonary rescue be performed in the event of a cardiac
      arrest. Studies on do not resuscitate decisions within oncology and hematology
      units, focusing on the specific role of the nurse in relation to these decisions,
      are scarce. OBJECTIVE: The aim of this study was to investigate hematology and
      oncology nurses' experiences and perceptions of do not resuscitate orders, in
      order to achieve a deeper understanding of the nurses' specific role in these
      decisions. RESEARCH DESIGN: A qualitative, descriptive methodology with
      individual semi-structured interviews was used. PARTICIPANTS AND RESEARCH
      CONTEXT: A total of 15 nurses from eight hematology/oncology wards in four
      hospitals in Sweden were interviewed individually. ETHICAL CONSIDERATIONS: In
      accordance with national regulations, an ethical review was not required for this
      study. The research followed international guidelines for empirical research, as
      outlined in the Helsinki Declaration. FINDINGS: The nurses strived for good
      nursing care through balancing harms and goods and observing integrity and
      quality of life as important values. Experienced hindrances for good care were
      unclear and poorly documented decisions, uninformed patients and relatives, and
      disagreements among the caregivers and family. The nurses expressed a need for an
      ongoing discussion on do not resuscitate decisions, including all concerned
      parties. CONCLUSION: In order to provide good nursing care, nurses need clear and
      well-documented do not resuscitate orders, and patients and relatives need to be
      well informed and included in the decisions. To increase the understanding for
      each other's opinions within the medical team, regular ethical discussions are
      required.

PMID- 24913544
TI  - Limits to relational autonomy--the Singaporean experience.
AB  - Recognition that the Principle of Respect for Autonomy fails to work in family
      centric societies such as Singapore has recently led to the promotion of
      relational autonomy as a suitable framework within which to place healthcare
      decision making. However, empirical data, relating to patient and family opinions
      and the practices of healthcare professionals in Confucian-inspired Singapore,
      demonstrate clear limitations on the ability of a relational autonomy framework
      to provide the anticipated compromise between prevailing family decision-making
      norms and adopted Western led atomistic concepts of autonomy. Evidence suggests
      that despite a growing infusion of Western influence, there is still little to
      indicate any major shift to individual decision making, particularly in light of
      the way society and healthcare are structured. Similarly, the lack of employing a
      shared decision-making model and data that discredit the notion that the complex
      psychosocial and cultural factors that affect the decision making may be
      considered "content neutral" not only prevents the application of relational
      autonomy but questions the viability of the values behind the Principle of
      Respect for Autonomy. Taking into account local data and drawing upon a wider
      concept of personhood that extends beyond prevailing family-centric ideals along
      with the complex interests that are focused upon the preservation of the unique
      nature of personhood that arises from the Ring Theory of Personhood, we propose
      and "operationalize" the employing of an authoritative welfare-based approach,
      within the confines of best interest decision making, to better meet the current
      care needs within Singapore.

PMID- 24913545
TI  - The experiences of people with dementia and intellectual disabilities with
      surveillance technologies in residential care.
AB  - BACKGROUND: Surveillance technology such as tag and tracking systems and video
      surveillance could increase the freedom of movement and consequently autonomy of
      clients in long-term residential care settings, but is also perceived as an
      intrusion on autonomy including privacy. OBJECTIVE: To explore how clients in
      residential care experience surveillance technology in order to assess how
      surveillance technology might influence autonomy. SETTING: Two long-term
      residential care facilities: a nursing home for people with dementia and a care
      facility for people with intellectual disabilities. METHODS: Ethnographic field
      study. ETHICAL CONSIDERATIONS: The boards representing clients and
      relatives/proxies of the clients were informed of the study and gave their
      written consent. The clients' assent was sought through a special information
      leaflet. At any time clients and/or proxy were given the option to withdraw from
      the study. The research protocol was also reviewed by a medical ethics committee.
      FINDINGS: Our findings show a pattern of two themes: (1) coping with new spaces
      which entailed clients: wandering around, getting lost, being triggered, and
      retreating to new spaces and (2) resisting the surveillance technology measure
      because clients feel stigmatized, missed the company, and do not like being
      "watched." CONCLUSION: Client experiences of surveillance technology appear to
      entail a certain ambivalence. This is in part due to the variety in surveillance
      technology devices, with each device bringing its own connotations and
      experiences. But it also lies in the devices' presupposition of an ideal user,
      which is at odds with the actual user who is inherently vulnerable. Surveillance
      technology can contribute to the autonomy of clients in long-term care, but only
      if it is set in a truly person-centered approach.

PMID- 24913546
TI  - Optimising assembly learning in older adults through the manipulation of
      instruction.
AB  - The present investigation assessed the putative benefits of reducing instructions
      for older adults' learning of an assembly task. Young and older adults had to
      build a product by assembling six components. Two groups practiced following
      instruction methods that differed in the degree of explicit information they
      conveyed about the correct assembly order. After practice, retention,
      consolidation of performance (tested immediately after practice and on a separate
      day, respectively) and stability of performance (tested by introducing a
      concurrent second task) were assessed. Younger adults showed similar performance
      levels for both instruction methods. Older adults, however, showed similar
      retention but clearly weaker consolidation and stability of performance following
      less encompassing instructions. Contrary to expectations, enhancing the
      involvement of explicit processes allowed older adults to gain a more permanent
      and stable performance improvements. The findings are discussed relative to the
      characteristics of the assembly task. PRACTITIONER SUMMARY: We addressed how
      performance and learning of older adults in an assembly task can be optimised
      through different types of instruction. The findings suggest that increasing
      awareness of task characteristics enhance not only long-term performance, but
      also resilience against distraction. Future work must evaluate if these findings
      generalise to more complex tasks.

PMID- 24913547
TI  - [Is coronary artery disease different in women?].
AB  - Coronary artery disease (CAD) is the primary cause of death in women. Although
      acute coronary syndrome (ACS) is relatively infrequent in young women, failure to
      recognize ACS in this population can incur a major risk and registry data show
      that there is still plenty of room for improvement in this area. Women may suffer
      from "classical" CAD with development of atherosclerosis with a delay of about 10
      years as compared to men, reflecting hormonal protection in women. Besides this
      classical presentation, angina in women often corresponds to impaired
      microcirculation, a syndrome known to associate typical angina, demonstrable
      myocardial ischemia, but no lesions on the coronary angiography. Finally, spasm,
      spontaneous dissection or coronary thrombosis through endothelial rupture are
      more frequent in women. The influence of risk factors on the development of CAD
      is comparable in both women and men. Recent registry studies show that in France,
      in particular, diabetes, obesity, and smoking are all risk factors that are on
      the rise in women. In addition, certain other risk factors are more specific to
      women, namely psycho-social stress. The methods to evaluate risk and detect CAD
      were mainly developed in male study populations, and these tools thus perform
      less well in female patients. In case of ACS, women benefit just as much from
      invasive management, but are at greater risk of iatrogenic complications,
      particularly with anti-thrombotic therapy or during revascularization procedures.

PMID- 24913548
TI  - Preventable mortality after common urological surgery: failing to rescue?
AB  - OBJECTIVE: To assess in-hospital mortality in patients undergoing many commonly
      performed urological surgeries in light of decreasing nationwide perioperative
      mortality over the past decade. This phenomenon has been attributed in part to a
      decline in 'failure to rescue' (FTR) rates, e.g. death after a complication that
      was potentially recognisable/preventable. PATIENTS AND METHODS: Discharges of all
      patients undergoing urological surgery between 1998 and 2010 were extracted from
      the Nationwide Inpatient Sample and assessed for overall and FTR mortality.
      Admission trends were assessed with linear regression. Logistic regression models
      fitted with generalised estimating equations were used to estimate the impact of
      primary predictors on over-all and FTR mortality and changes in mortality rates.
      RESULTS: Between 1998 and 2010, an estimated 7,725,736 urological surgeries
      requiring hospitalisation were performed in the USA; admissions for urological
      surgery decreased 0.63% per year (P = 0.008). Odds of overall mortality decreased
      slightly (odds ratio [OR] 0.990, 95% confidence interval [CI] 0.988-0.993), yet
      the odds of mortality attributable to FTR increased 5% every year (OR 1.050, 95%
      CI 1.038-1.062). Patient age, race, Charlson Comorbidity Index, public insurance
      status, as well as urban hospital location were independent predictors of FTR
      mortality (P < 0.001). CONCLUSION: A shift from inpatient to outpatient surgery
      for commonly performed urological procedures has coincided with increasing rates
      of FTR mortality. Older, sicker, minority group patients and those with public
      insurance were more likely to die after a potentially recognisable/preventable
      complication. These strata of high-risk individuals represent ideal targets for
      process improvement initiatives.

PMID- 24913550
TI  - The Politics of Psychoanalytic Lexicography.

PMID- 24913549
TI  - MicroRNAs play a role in spontaneous recovery from acute liver failure.
AB  - Acute liver failure (ALF) represents a life-threatening situation characterized
      by sudden and massive liver cell death in the absence of preexisting liver
      disease. Although most patients require liver transplantation to prevent
      mortality, some recover spontaneously and show complete liver regeneration.
      Because of the rarity of this disease, the molecular mechanisms regulating liver
      regeneration in ALF patients remain largely unknown. In this study, we
      investigated the role of microRNAs (miRs) that have been implicated in liver
      injury and regeneration in sera from ALF patients (n = 63). Patients with
      spontaneous recovery from ALF showed significantly higher serum levels of miR
      122, miR-21, and miR-221, compared to nonrecovered patients. In liver biopsies,
      miR-21 and miR-221 displayed a reciprocal expression pattern and were found at
      lower levels in the spontaneous survivors, whereas miR-122 was elevated in both
      serum and liver tissue of those patients. As compared to nonrecovered patients,
      liver tissue of spontaneous survivors revealed not only increased hepatocyte
      proliferation, but also a strong down-regulation of miRNA target genes that
      impair liver regeneration, including heme oxygenase-1, programmed cell death 4,
      and the cyclin-dependent kinase inhibitors p21, p27, and p57. CONCLUSION: Our
      data suggest that miR-122, miR-21, and miR-221 are involved in liver regeneration
      and might contribute to spontaneous recovery from ALF. Prospective studies will
      show whether serological detection of those miRNAs might be of prognostic value
      to predict ALF outcome.

PMID- 24913552
TI  - Effective Treatment Strategies for Autism During the First Five Years of
      Development.

PMID- 24913551
TI  - Transforming Trauma: The Relational Unconscious and "Chemistry" in the Treatment
      of a Paraplegic Patient.
AB  - Therapeutic action with a traumatized paraplegic patient highlights the evocative
      and transformative-influence of the relational unconscious. The patient's
      triumphant resolution suggests that formative bipersonal dynamics (including
      transference, countertransference, and mutual projective identifications) create
      an ongoing intersubjective enactment and relational chemistry pivotal to psychic
      shift. A broad systems perspective highlights contextual communication and the
      interweaving of the analyst's etiological contributions and subjective experience
      of trauma. Ultimately, an unconscious, co-created dynamic challenges traumatic
      fixations, supporting a reintegration of narcissistic, gender, and erotic
      representations and ego capacities. An eclectic perspective that illuminates the
      analyst's role-receptivity encompasses classical, object relations, relational,
      systems, and self psychological paradigms.

PMID- 24913554
TI  - Use of dual-energy CT and virtual non-calcium techniques to evaluate post
      traumatic bone bruises in knees in the subacute setting.
AB  - OBJECTIVE: The purpose of this study was to determine the ability of dual-energy
      computed tomography (DECT) and virtual non-calcium (VNCa) imaging to detect
      magnetic resonance imaging (MRI)-demonstrated bone bruises several weeks after
      unilateral knee injury. MATERIALS AND METHODS: Patients with unilateral knee
      injury and MRI-confirmed bone bruises who had undergone a DECT scan of both knees
      were retrospectively identified. Two radiologists evaluated VNCa images for
      bruises in four regions per knee without knowing the MRI results. The mean CT
      numbers were calculated for the lesion-positive and lesion-negative regions of
      the injured knee, and the contralateral knee. RESULTS: Fourteen patients with a
      total of 36 regions positive for bone bruises on MRI were identified. The median
      delay between injury and DECT was 37 days (range, 11-99 days). The mean CT
      numbers in VNCa images for lesion-positive and lesion-negative regions were -7.6
      +/- 24.9 HU and -58.2 +/- 19.5 HU, respectively. There were no significant
      differences in mean CT number between the lesion-negative regions in the injured
      knee and the contralateral knee. No resolution of bruising was seen before week
      5, and bone bruising was still identifiable in one out of the two patients
      scanned at 10 weeks following injury. CONCLUSIONS: DECT and VNCa images can
      identify bone bruising for at least 10 weeks after injury.

PMID- 24913553
TI  - Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers.
AB  - NF1 encodes a RAS GTPase-activating protein. Accordingly, aberrant RAS activation
      underlies the pathogenesis of NF1-mutant cancers. Nevertheless, it is unclear
      which RAS pathway components represent optimal therapeutic targets. Here, we
      identify mTORC1 as the key PI3K effector in NF1-mutant nervous system
      malignancies and conversely show that mTORC2 and AKT are dispensable. However, we
      find that tumor regression requires sustained inhibition of both mTORC1 and MEK.
      Transcriptional profiling studies were therefore used to establish a signature of
      effective mTORC1-MEK inhibition in vivo. We unexpectedly found that the glucose
      transporter GLUT1 was potently suppressed, but only when both pathways were
      inhibited. Moreover, unlike VHL- and LKB1-mutant cancers, reduction of (18)F-FDG
      uptake required the suppression of both mTORC1 and MEK. Together, these studies
      identify optimal and suboptimal therapeutic targets in NF1-mutant malignancies
      and define a noninvasive means of measuring combined mTORC1-MEK inhibition in
      vivo, which can be readily incorporated into clinical trials. SIGNIFICANCE: This
      work demonstrates that mTORC1 and MEK are key therapeutic targets in NF1-mutant
      cancers and establishes a noninvasive biomarker of effective, combined target
      inhibition that can be evaluated in clinical trials.

PMID- 24913555
TI  - Isolated avulsion fracture at the medial head of the gastrocnemius muscle.
AB  - An isolated avulsion fracture involving the femoral origin of the medial head of
      the gastrocnemius muscle without an associated muscular, meniscal, or ligamentous
      injury is extremely rare. We report a case of a 14-year-old male wrestler who
      presented with a radiographically occult avulsion fracture of the medial
      gastrocnemius tendon sustained during competition. To our knowledge, this is the
      first case to describe a mechanism of injury as well as to report a return to
      competition after non-operative management. 

PMID- 24913556
TI  - MRI of transforaminal lumbar interbody fusion: imaging appearance with and
      without the use of human recombinant bone morphogenetic protein-2 (rhBMP-2).
AB  - PURPOSE: To describe the vertebral endplate and intervertebral disc space MRI
      appearance following TLIF, with and without the use of rhBMP-2, and to determine
      if the appearance is concerning for discitis/osteomyelitis. MATERIALS AND
      METHODS: After institutional review board approval, 116 TLIF assessments
      performed on 75 patients with rhBMP-2 were retrospectively and independently
      reviewed by five radiologists and compared to 73 TLIF assessments performed on 45
      patients without rhBMP-2. MRIs were evaluated for endplate signal, disc space
      enhancement, disc space fluid, and abnormal paraspinal soft tissue. Endplate
      edema-like signal was reported when T1-weighted hypointensity, T2-weighted
      hyperintensity, and endplate enhancement were present. Subjective concern for
      discitis/osteomyelitis on MRI was graded on a five-point scale. Generalized
      estimating equation binomial regression model analysis was performed with
      findings correlated with rhBMP-2 use, TLIF level, graft type, and days between
      TLIF and MRI. RESULTS: The rhBMP-2 group demonstrated endplate edema-like signal
      (OR 5.66; 95% CI [1.58, 20.24], p = 0.008) and disc space enhancement (OR 2.40;
      95% CI [1.20, 4.80], p = 0.013) more often after adjusting for the TLIF level,
      graft type, and the number of days following TLIF. Both groups had a similar
      temporal distribution for endplate edema-like signal but disc space enhancement
      peaked earlier in the rhBMP-2 group. Disc space fluid was only present in the
      rhBMP-2 group. Neither group demonstrated abnormal paraspinal soft tissue and
      discitis/osteomyelitis was not considered likely in any patient. CONCLUSIONS:
      Endplate edema-like signal and disc space enhancement were significantly more
      frequent and disc space enhancement developed more rapidly following TLIF when
      rhBMP-2 was utilized. The concern for discitis/osteomyelitis was similar and
      minimal in both groups.

PMID- 24913557
TI  - DNA and RNA analysis of blood and muscle from bodies with variable postmortem
      intervals.
AB  - The breakdown of DNA and RNA in decomposing human tissue represents a major
      obstacle for postmortem forensic molecular analysis. This study investigated the
      feasibility of performing PCR-based molecular analysis of blood and muscle tissue
      from 45 autopsy cases with defined postmortem intervals ranging from one to more
      than 14 days. It was not possible to collect blood from 38 % of the autopsy cases
      due to severe coagulation and hemolysis, whereas muscle tissue was available for
      all cases. PCR-amplifiable DNA could be extracted from 96 % of the frozen muscle
      specimens and from 93 % of the formalin fixed and paraffin embedded (FFPE) muscle
      specimens. A quality assessment of muscle-derived DNA showed increased
      fragmentation with advancing body decomposition and generally more fragmentation
      in DNA from FFPE tissue than in DNA from frozen tissue. It was possible to
      amplify 1,000 basepair (bp) DNA fragments from all samples with postmortem
      intervals below 3 days whereas 400-600 bp long fragments typically could be
      amplified from the most decomposed muscle specimens. RNA was less stable than DNA
      in postmortem muscle tissue, yet selected mRNA molecules could be detected by
      reverse-transcriptase PCR in all samples up to 3 days after death. We conclude
      that analysis of DNA from bodies with a wide postmortem interval range is usually
      possible whereas the consistency of RNA analyses decreases considerably 3 days
      postmortem. We showed that muscle tissue is a highly usable source of DNA and RNA
      for postmortem forensic molecular analysis as well as for retrospective research
      projects based on archived FFPE specimens. 

PMID- 24913558
TI  - Eremophilane-type sesquiterpenoids with diverse skeletons from Ligularia sagitta.
AB  - Five new highly oxygenated eremophilane-type sesquiterpenoids, possessing C19 (1
      and 2), C15 (3 and 4), and C14 (8) skeletons, along with eight known
      eremophilenolides were obtained from the aerial parts of Ligularia sagitta. The
      absolute configuration of 1 was assigned by X-ray diffraction analysis and that
      of 3 by ECD spectroscopy. Compounds 1-10 were evaluated for their antibacterial
      activities against Staphyloccocus aureus, Bacillus subtilis, Escherichia coli,
      Bacillus cereus, and Erwinia carotovora. Compounds 4 and 5 displayed broad
      spectrum inhibitory activity against these bacteria with MIC values of
      approximately 7.25 MUg/mL, followed by 3 and 6 with MIC values in the range of
      23.0-125.0 MUg/mL. Compounds 3 and 8 showed mild activity against three human
      tumor cell lines (IC50 ~ 13 MUM). Preliminary structure-activity relationships
      for these eremophilenolides are reported. 

PMID- 24913559
TI  - Probiotic assessment of Enterococcus durans 6HL and Lactococcus lactis 2HL
      isolated from vaginal microflora.
AB  - Forty-five lactic acid bacteria (LAB) were isolated from the vaginal specimens of
      healthy fertile women, and the identities of the bacteria were confirmed by
      sequencing of their 16S rDNA genes. Among these bacteria, only four isolates were
      able to resist and survive in low pH, bile salts and simulated in vitro digestion
      conditions. Lactococcus lactis 2HL, Enterococcus durans 6HL, Lactobacillus
      acidophilus 36YL and Lactobacillus plantarum 5BL showed the best resistance to
      these conditions. These strains were evaluated further to assess their ability to
      adhere to human intestinal Caco-2 cells. Lactococcus lactis 2HL and E. durans 6HL
      were the most adherent strains. In vitro tests under neutralized pH proved the
      antimicrobial activity of both strains. Results revealed that the growth of
      Escherichia coli O26, Staphylococcus aureus and Shigella flexneri was suppressed
      by both LAB strains. The antibiotic susceptibility tests showed that these
      strains were sensitive to all nine antibiotics: vancomycin, tetracycline,
      ampicillin, penicillin, gentamicin, erythromycin, clindamycin, sulfamethoxazole
      and chloramphenicol. These data suggest that E. durans 6HL and Lactococcus lactis
      2HL could be examined further for their useful properties and could be developed
      as new probiotics. 

PMID- 24913560
TI  - Zinc enhances the phototoxic effect of blue light against malodour-producing
      bacteria in an experimental oral biofilm.
AB  - Oral malodour is thought to be caused mainly by the production of volatile
      sulfide compounds (VSCs) by anaerobic Gram-negative oral bacteria. Previous
      studies have shown that these bacteria are susceptible to blue light (400-500 nm
      wavelength). In the present study, we tested the effect of blue light in the
      presence of zinc, erythrosine B or both on malodour production in an experimental
      oral biofilm. Biofilms were exposed to a plasma-arc light source for 30, 60 and
      120 s (equal to energy fluxes of 41, 82 and 164 J cm(-2), respectively) with or
      without the addition of zinc acetate, erythrosine B or both. After the light
      exposure, biofilm samples were examined for malodour production (by an odour
      judge) and VSC production (with a Halimeter), and VSC-producing bacteria were
      quantified using a microscopy-based sulfide assay (MSA) and in situ confocal
      laser scanning microscopy (CLSM). Results showed that exposing experimental oral
      biofilm to both blue light and zinc reduced malodour production, which coincided
      with a reduction in VSC-producing bacteria in the biofilm. These results suggest
      that zinc enhances the phototoxicity of blue light against malodour-producing
      bacteria. 

PMID- 24913561
TI  - MicroRNA expression in mice infected with seasonal H1N1, swine H1N1 or highly
      pathogenic H5N1.
AB  - Influenza virus infections in humans remain a healthcare concern, and the need
      for vaccines, therapeutics and prophylactics remains a high priority.
      Understanding the molecular events associated with influenza-virus-induced
      pathology may lead to the identification of clinical disease biomarkers and novel
      antiviral targets. MicroRNAs (miRNAs) are well-conserved endogenous non-coding
      RNAs known to regulate post-transcriptional gene expression as well as play a
      major role in many biological processes and pathways. Animal studies have
      demonstrated that miRNAs are involved in viral disease and controlling
      inflammation. In this study, we examined the differences in the miRNA expression
      profiles associated with the lung in mice infected with influenza viruses that
      varied in virulence and pathogenicity. A statistical model was employed that
      utilized changes in miRNA expression to identify the virus that was used to
      infect the mice. This study identified a unique fingerprint of viral
      pathogenicity associated with seasonal H1N1, swine H1N1 and highly pathogenic
      H5N1 in the mouse model, and may lead to the identification of novel therapeutic
      and prophylactic targets. 

PMID- 24913562
TI  - Combination therapy with thioridazine and dicloxacillin combats meticillin
      resistant Staphylococcus aureus infection in Caenorhabditis elegans.
AB  - The shortage of drugs active against meticillin-resistant Staphylococcus aureus
      (MRSA) is a growing clinical problem. In vitro studies indicate that the
      phenothiazine thioridazine (TZ) might enhance the activity of the beta-lactam
      antibiotic dicloxacillin (DCX) to a level where MRSA is killed, but experiments
      in simple animal models have not been performed. In the present study, we
      introduced Caenorhabditis elegans infected by S. aureus as an in vivo model to
      test the effect of TZ as a helper drug in combination with DCX. Because TZ is an
      anthelmintic, initial experiments were carried out to define the thresholds of
      toxicity, determined by larval development, and induction of stress-response
      markers. No measurable effects were seen at concentrations of less than 64 mg TZ
      l(-1). Seven different MRSA strains were tested for pathogenicity against C.
      elegans, and the most virulent strain (ATCC 33591) was selected for further
      analyses. In a final experiment, full-grown C. elegans were exposed to the test
      strain for 3 days and subsequently treated with 8 mg DCX l(-1) and 8 mg TZ l(-1)
      for 2 days. This resulted in a 14-fold reduction in the intestinal MRSA load as
      compared with untreated controls. Each drug alone resulted in a two- to threefold
      reduction in MRSA load. In conclusion, C. elegans can be used as a simple model
      to test synergy between DCX and TZ against MRSA. The previously demonstrated in
      vitro synergy can be reproduced in vivo. 

PMID- 24913563
TI  - Polyethyleneimine and polyethyleneimine-based nanoparticles: novel bacterial and
      yeast biofilm inhibitors.
AB  - Biofilms are commonly involved in medical device-related infections. The purpose
      of this study was to determine the antimicrobial and anti-biofilm activity of
      polyethyleneimine (PEI) and PEI-based nanoparticles (nanoPEI) against
      Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter baumannii and
      Candida albicans (clinical and ATCC strains), and to evaluate their effect upon
      biofilm formation on polyurethane (PUR)-like catheters. MICs and minimal lethal
      concentrations of PEI and nanoPEI were determined according to CLSI microdilution
      reference protocols. For PEI, the MIC value was 195.31 mg l(-1) for all the
      bacteria and 48.83 mg l(-1) for the yeast strains. For nanoPEI, the MIC value was
      1250 mg l(-1) for all the strains except A. baumannii, for which it was 2500 mg
      l(-1). Biofilm formation was assessed with PUR-like catheter segments and biofilm
      metabolic activity was quantified by colorimetry with a tetrazolium reduction
      assay. Plasma membrane integrity and membrane potential were assessed by flow
      cytometry after staining microbial cells with a membrane-impermeable dye,
      propidium iodide, and a membrane-potential marker, DiBAC4(3). PEI inhibited
      growth of all microbial species; higher concentrations of nanoPEI were needed to
      inhibit growth of all species. Biofilm formation in the presence of anti
      bacterial PEI activity was dose-dependent (except for S. epidermidis) and species
      related. NanoPEI at 0.5*MIC and MIC significantly reduced the metabolic activity
      of biofilms of S. aureus, S. epidermidis and A. baumannii, whereas 2*MIC was
      required in order to inhibit biofilm metabolic activity. 

PMID- 24913564
TI  - Patients with anatomically "simple" renal masses are more likely to be placed on
      active surveillance than those with anatomically "complex" lesions.
AB  - OBJECTIVE: To determine if radiographically less complex renal lesions are deemed
      clinically less "worrisome" and therefore are more likely to be considered for
      active surveillance (AS). METHODS: We examined our prospective institutional
      database to identify and compare patients with localized renal cell carcinoma
      undergoing an initial period of AS or immediate surgery. Multivariate logistic
      regression was used to examine covariates associated with receipt of AS. RESULTS:
      Of 1,059 patients with available anatomic complexity data, 195 underwent an
      initial period of AS (median duration of AS 25.6 mo [interquartile range: 11.8
      52.8 mo]). Compared with patients undergoing immediate surgical treatment,
      patients selected for AS had lower overall nephrometry scores (NS) with tumors
      that were smaller, further from the sinus or urothelium, more often polar, and
      less often hilar (P<0.0015 all comparisons). After adjustment for age, largest
      tumor size, individual components of NS, total NS, and Charlson comorbidity
      index, total NS (odds ratio [OR] = 1.9 [CI: 1.4-2.5]), "R" score of 1 (OR = 5.2
      [CI: 1.8-15.2]), "N" score of 1 (OR = 2.3 [CI: 1.5-3.6]), "L" score of 1 (OR =
      1.4 [CI: 0.84-2.2]), and nonhilar tumor location (OR = 2.7 [CI: 1.2-5.8])
      increased the probability of being selected for AS compared with immediate
      surgery. Findings remained significant in a subanalysis of T1a renal masses.
      CONCLUSIONS: Lower tumor anatomic complexity was strongly associated with the
      decision to proceed with AS in patients with stage I renal mass. Not only may
      these data afford new insights into renal mass treatment trends, but the findings
      may also prove useful in the development of objective protocols to most
      appropriately select patients for AS.

PMID- 24913565
TI  - Spectroscopic characterization of Co3O4 catalyst doped with CeO2 and PdO for
      methane catalytic combustion.
AB  - The study deals with the XPS, Raman and EDX characterization of a series of
      structured catalysts composed of cobalt oxides promoted by palladium and cerium
      oxides. The aim of the work was to relate the information gathered from
      spectroscopic analyses with the ones from kinetic tests of methane combustion to
      establish the basic structure-activity relationships for the catalysts studied.
      The most active catalyst was the cobalt oxide doped with little amount of
      palladium and wins a confrontation with pure palladium oxide catalyst which is
      commercially used in converters for methane. The analyses Raman and XPS analyses
      showed that this catalyst is composed of a cobalt spinel and palladium oxide. The
      quantitative approach to the composition of the catalysts by XPS and EDX methods
      revealed that the surface of palladium doped cobalt catalyst is enriched with
      palladium oxide which provides a great number of active centres for methane
      combustion indicated by kinetic parameters. 

PMID- 24913566
TI  - Molecular mechanism of resistance of Fusarium fujikuroi to benzimidazole
      fungicides.
AB  - Although carbendazim (MBC) and other benzimidazole fungicides have effectively
      controlled bakanae disease of rice (which is caused by Fusarium fujikuroi, F.
      proliferatum, and F. verticillioides) in the past, MBC resistance has become
      common. Previous research has shown that MBC resistance results from a mutation
      in the beta1 -tubulin (beta1 tub) gene in F. verticillioides. However, MBC
      resistance in F. fujikuroi, a predominant species in China, does not result from
      a mutation in the beta1 tub. The molecular mechanism of F. fujikuroi resistance
      against benzimidazole fungicides is poorly understood. In this study, we
      determined that although beta1 tub and beta2 -tubulin (beta2 tub) in F. fujikuroi
      have high homology with beta1 tub and beta2 tub in F. verticillioides, MBC
      resistance in F. fujikuroi results from mutations in beta2 tub [GAG(Glu)
      >GTG(Val) at codon 198, TTC(Phe)->TAC(Tyr) at codon 200, and GGC(Gly)->GGT(Gly)
      at codon 235] but not in beta1 tub. Deltabeta2 tub (beta2 tub deletion) mutants
      were highly sensitive to MBC, produced fewer conidia and were less virulent than
      parental strains. Complementation of the Deltabeta2 tub mutants with a copy of
      the whole beta2 tub locus from their parental strains restored the level of MBC
      resistance (or sensitivity) to that of the parental strain.

PMID- 24913567
TI  - miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer
      cells through PACE4 pathway.
AB  - INTRODUCTION: PACE4 plays an important role in prostate cancer (PCa)
      proliferation and aggression, which might provide a useful target against
      prostate cancer. In this study, we had strived to find some key miRNAs to
      decrease malignancy and invasiveness of PCa through regulating PACE4 expression.
      METHODS: Clinically pathological analysis of immunohistochemistry/in situ
      hybridization was carried out to detect the relationship between PACE4
      expression/miRNAs and the malignancy of prostate mass. Prostate cell lines
      (DU145, C4-2, and BPH-1) were cultured for growth curve, immunocytochemistry
      analysis, colony formation, Matrigel invasion, and transcriptional/translational
      expression assay of PACE4-related signaling molecules for confirming the
      relationship. MiRNAs targeting PACE4 were predicted, validated and further
      corroborated using bio-software, real-time PCR, luciferase reporter assay and
      transfection of miRNA mimics and inhibitor. RESULTS: It was suggested that PACE4
      might reflect the pathological malignancy of prostate lesion from pathology
      analysis. Moreover, DU145 cells, the highest PACE4-level and related TF
      expression indicated of the strongest malignancy and invasiveness. It was
      significantly found that miR-124 was presented with the biggest odd to target
      PACE4-3'UTR, the capability of decreasing PACE expression and slowing down cell
      growth and cell invasion. CONCLUSIONS: It was clear that PACE4 level was closely
      associated with malignancy and invasiveness of PCa in vivo or in vitro MiR-124,
      played a crucial role inhibiting PACE4 transcription thus exhibiting obvious
      effects of antiproliferation and antiaggression of PCa.

PMID- 24913568
TI  - Molecular characterization of 54 cases of false-negative fine-needle aspiration
      among 1347 papillary thyroid carcinomas.
AB  - BACKGROUND: Fine-needle aspiration (FNA) has been widely accepted as the most
      crucial step in the preoperative assessment of thyroid nodules, but the false
      negative rates are generally reported to be between 3.6% and 10.2%. To lower the
      overall incidence of this false-negative testing, new reporting systems encourage
      the molecular testing of thyroid nodules. However, to the authors' knowledge, the
      role of molecular testing in false-negative FNA has not yet been evaluated.
      METHODS: In total, 1347 consecutive papillary thyroid carcinomas (PTCs) with both
      cytological and histological diagnoses were collected from the same center. A
      blinded revision of the false-negative cases was performed. An analysis of the
      BRAF and Ras genes in the false-negative cases was then performed. RESULTS: The
      false-negative rate at the time of primary FNA diagnosis was 4.8% (65 of 1347
      cases). False-negative cases were 15 follicular variant PTCs, 2 classical
      variant, and 1 solid variant that lacked peculiar PTC cytomorphological features.
      Adequate cellular material for molecular analysis was available only in 54 of the
      65 false-negative cases. Mutations were found in 6 cases (11%), and Ras
      alterations were present in 16 cases (29.6%). The addition of molecular analysis
      decreased the false-negative rate to 0.4% (5 of 1347 cases). CONCLUSIONS: The
      results of the current study confirm the feasibility of BRAF and Ras analysis in
      routine FNA. However, when the false-negative FNA rate is low, the cost-benefit
      analysis of the detection of BRAF and Ras mutations should be carefully
      evaluated. Consequently, the authors suggest that preoperative molecular
      assessment could be helpful for benign nodules, but only in the presence of
      clinical suspicion of malignancy.

PMID- 24913569
TI  - Accumulation of microvascular target organ damage in newly diagnosed hypertensive
      patients.
AB  - Early identification of hypertensive target organ damage (TOD) emerges as
      important for global cardiovascular risk assessment. Retinal vascular
      alterations, capillary rarefaction, and microalbuminuria represent different
      forms of microvascular TOD. However, data regarding their concomitant presence in
      the early stages of hypertension, the association of the number of affected
      organs with cardiovascular risk, and aldosterone effect on multiple TOD are
      lacking. We studied naive, never-treated patients with recent duration of
      hypertension and healthy volunteers. Innovative software was developed to
      estimate retinal vascular diameters and capillary density. Biochemical parameters
      including microalbuminuria and serum aldosterone were derived. Framingham Risk
      Score was used to determine cardiovascular risk. In total 103 subjects, 66
      hypertensives and 37 normotensives, were included. Hypertensive patients
      exhibited a greater number of affected target organs compared with normotensives
      (P = .014), with retinopathy and capillary rarefaction (40.9%) representing the
      most common TOD among hypertensives. The number of affected organs was linearly
      correlated with increased Framingham score and serum aldosterone, analyzed with
      univariate (P < .001 and P = .002) and multivariate analysis (P = .025 and P =
      .004), respectively. Physicians dealing with hypertensive patients should be
      aware of the possibility of diffuse microvascular impairment and seek multiple
      TOD even in the early stages of hypertension. 

PMID- 24913570
TI  - Long-term renin-angiotensin blocking therapy in hypertensive patients with normal
      aorta may attenuate the formation of abdominal aortic aneurysms.
AB  - Renin-angiotensin system (RAS) has been implicated in the pathogenesis of
      abdominal aortic aneurysm (AAA). Angiotensin II type 1 receptor blocker (ARB),
      when given with angiotensin II prevents AAA formation in mice, but found
      ineffective in attenuating the progression of preexisting AAA. This study was
      designed to evaluate the effect of chronic RAS blockers on abdominal aortic
      diameter in hypertensive patients without known aortic aneurysm. Consecutive
      hypertensive outpatients (n = 122) were stratified according to antihypertensive
      therapy they received for 12 months or more, consisting of ARB (n = 45),
      angiotensin converting enzyme inhibitor (ACE-I; n = 45), or nonARB/nonACE-I
      (control therapy; n = 32). Abdominal ultrasonography was performed to measure
      maximal subrenal aortic diameter. Eighty-four patients were reexamined by
      ultrasonography 8 months later. The correlation between the different
      antihypertensive therapies and aortic diameter was examined. Aortic diameters
      were significantly smaller in ARB than in control patients in the baseline and
      follow-up measurements (P = .004; P = .0004, respectively). Risk factor adjusted
      covariance analysis showed significant differences between ARB or ACE-I treated
      groups and controls (P = .006 or P = .046, respectively). Ultrasound that was
      performed 8 months later showed smaller increases in mean aortic diameters of the
      ARB and ACE-I groups than in controls. Both ARB and ACE-I therapy attenuated
      expansion of nonaneurysmal abdominal aorta in humans. These results indicate that
      RAS blockade given before advancement of aortic medial remodeling may slow down
      the development of AAA. 

PMID- 24913571
TI  - Effect of erythropoietin on free radical oxidation and glycoprotein expression in
      platelets under conditions of chronic renal failure.
AB  - A short-term open prospective study examined 62 patients at the terminal stage of
      chronic renal failure. The experimental group received erythropoietin in a total
      dose of about 40,000 U. The expression of glycoproteins IIb-IIIa, IIb, and Ib was
      enhanced, the content of LPO products was elevated, and SOD and catalase
      activities were reduced in platelets from patients with chronic renal failure.
      Administration of erythropoietin partially restored free radical oxidation and
      expression of glycoproteins IIb-IIIa, IIb, and Ib in platelets. A significant
      correlation was revealed between the expression of platelet receptors on the one
      hand, and content of LPO products and SOD and catalase activities, on the other
      hand. 

PMID- 24913572
TI  - Production of corticosteroid hormones in vitro by adrenals in rats with
      streptozotocin-induced diabetes.
AB  - We studied baseline and ACTH-stimulated in vitro production of corticosteroids by
      rat adrenals. Production of the basic corticosteroids pregnenolone (early
      precursor in corticosteroid synthesis), progesterone (intermediate precursor in
      synthesis of gluco- and mineralocorticoid hormones), and corticosterone (major
      glucocorticoid hormone in rodents) in animals with streptozotocin-induced
      diabetes was enhanced by 1.8-2.0 times in comparison with the control animals.
      Addition of ACTH to the incubation medium stimulated pregnenolone production by
      the adrenals equally in the control and experimental (diabetic) groups, while the
      increase in corticosterone production was less pronounced in the experimental
      group. Stimulation of corticosterone production in response to ACTH after
      saturation of the incubation medium with pregnenolone was also less pronounced in
      diabetic rats. 

PMID- 24913573
TI  - GABA derivatives citrocard and salifen reduce the intensity of experimental
      gestosis.
AB  - Substitution of drinking water with 1.8 % NaCl solution in pregnant female rats
      from day 1 of gestation until parturitions was followed by the development of
      experimental gestosis. Gestosis manifested in an increase in BP by 18.2 %,
      protein concentration in the urine by 6.2 times, and edema severity in muscles,
      brain, and omentum in comparison with the initial level. The concentration of
      homocysteine in blood plasma of rats with complicated pregnancy 4.4-fold
      surpassed that in pregnant rats without gestosis, which can probably in a cause
      for gestosis development. GABA derivatives citrocard (50 mg/kg) and salifen (15
      mg/kg), and the reference substance sulodexide (30 U/kg) reduced the severity of
      gestosis manifestations, which was seen from the absence of BP rise, decrease in
      urinary protein concentration by 1.9, 2.0, and 1.3 times and blood level of
      homocysteine by 1.7, 1.5, and 2.6 times, respectively, and a decrease in edema
      degree in comparison with female rats with experimental gestosis receiving
      physiological saline. 

PMID- 24913574
TI  - Variability of cytometric parameters in various clusters of interstitial
      endocrine cells of testicles in CBA * C57Bl6 mice during experimental chrome
      benzene intoxication.
AB  - Chromium-benzene intoxication was associated with not only damage to tissue
      elements of the testicles, but also realization of the adaptive mechanisms
      protecting endocrine active structures in male CBA * C57Bl6 mice. Quantitative
      substantiation of the transformation processes, their direction, relationships,
      and attained levels were obtained. 

PMID- 24913575
TI  - Effects of fullerenol C60(OH)24 on erythropoiesis in vitro.
AB  - The effects of fullerenol C60(OH)24 in doses of 0.1-100 MUg/ml on erythropoiesis
      were studied in the culture of erythroblastic islets of the bone marrow.
      Fullerenol in concentrations of 10 and 100 MUg/ml had negative effects on the
      development of erythroid tissue: it inhibits proliferation of erythroid cells,
      delays erythroblast maturation, decelerates recruitment of erythroid CFU to
      differentiation, and suppresses repeated involvement of macrophages in
      erythroblastic islets. 

PMID- 24913576
TI  - Efficacy of peptide anxiolytic selank during modeling of withdrawal syndrome in
      rats with stable alcoholic motivation.
AB  - We studied the effects of selank on the development of symptoms of acute 48-h
      alcohol withdrawal in outbred rats drinking 10 % ethanol as the only source of
      fluid for 24 weeks. In alcohol-preferring animals (mean daily ethanol intake >5.0
      g/kg) allowed free choice between 10 % ethanol and water, single intraperitoneal
      injection of selank in a dose of 0.3 mg/kg eliminated anxiety induced by ethanol
      withdrawal in tests elevated plus maze and social interaction tests and prevented
      the formation of mechanical allodynia without affecting ethanol consumption. The
      fi ndings suggest that selank is effective in eliminating of alcohol withdrawal
      symptoms in rats.

PMID- 24913577
TI  - Effect of transplants of retinal pigment epithelial cells from adult human eye on
      degenerative processes in the brain of rats with experimental acute hypoxia.
AB  - Stimulation of cell regeneration in the brain and eye retina in various
      degenerative processes is a pressing problem in neurobiology. A promising
      approach is transplantation of somatic cells reprogrammed towards neural lineage.
      We studied the effect of transplantation of retinal pigment epithelial cells from
      adult human eye transdifferentiated in culture on degenerative processes in the
      brain of rats subjected to acute hypoxia. Immunohistochemical and molecular
      genetic analysis suggests that retinal pigment epithelial cells
      transdifferentiate in vitro and express markers of low-differentiated neural
      cells. The cells transplanted into rat brain survive for at least 20 days. During
      this period, they stimulate compensatory and reparative processes that protected
      cortical neurons in the recipients from hypoxia-induced degeneration. 

PMID- 24913578
TI  - Effect of spiperone on mesenchymal multipotent stromal and hemopoietic stem cells
      under conditions of pulmonary fibrosis.
AB  - The antifibrotic properties of spiperone and its effect on stem and progenitor
      cells were studied on the model of reversible bleomycin-induced pulmonary
      fibrosis in C57Bl/6 mice. Spiperone reduced infiltration of the alveolar
      interstitium and alveolar ducts with inflammatory cells and prevented the growth
      of the connective tissue in the parenchyma of bleomycin lungs. Apart from anti
      inflammatory effect, spiperone suppressed bone marrow hemopoietic cells (CD3,
      CD45R (B220), Ly6C, Ly6G (Gr1), CD11b (Mac1), TER-119)-, Sca-1+, c-Kit+, CD34-
      and progenitor hemopoietic cells (granulocyte-erythroid-macrophage-megakaryocytic
      and granulocyte CFU). Spiperone-induced disturbances of fi brogenesis were
      paralleled by restoration of endothelial cells in the lung parenchyma, reduction
      of the number of circulating bone marrow cells and lung mesenchymopoietic cells
      (mesenchymal multipotent stromal cells (CD31-, CD34-, CD45-, CD44+, CD73+, CD90+,
      CD106+) and progenitor fi broblast cells), and suppression of multilineage
      differentiation of multipotent mesenchymal stromal cells (including fi broblast
      lineage cells).

PMID- 24913579
TI  - Comparison of the efficiency of transplantation of bone marrow multipotent
      mesenchymal stromal cells cultured under normoxic and hypoxic conditions and
      their conditioned media on the model of acute lung injury.
AB  - The therapeutic efficiency of intravenous injection of rat bone marrow
      multipotent mesenchymal stromal cells grown under conditions of normoxia and
      hypoxia (3% O2) and conditioned media from these cultures were compared on the
      rat model of acute lung injury induced by intraperitoneal injection of
      lipopolysaccharide. The best therapeutic efficiency was demonstrated by cells
      grown under hypoxic conditions. The effect of conditioned media was less
      pronounced and did not depend on the culturing conditions. 

PMID- 24913581
TI  - Modification of human fibroblast properties in microtransplant.
AB  - We studied the properties of human skin fibroblast in filamentous polyglycolic
      microtransplant. Fibroblast adhesion to the microtransplant filaments is followed
      by the formation of a network cross-linked with fibroblasts. The cells rapidly
      proliferate during the first few days; after transfer of the microtransplant to
      the standard culture flask, the cells migrate to the plastic and continue
      proliferation. The cells are uniform and exhibit high colony-formation capacity.
      The bundles of microtransplant filaments persist in the culture for several days
      and through the cells completely leave them, the area around these filaments
      remains the most populated for 40 days. Mitotic cells are seen in the immediate
      proximity to the degrading filaments of the transplant. The effect of cell
      "rejuvenation" in the microtransplant can be explained by selection of cells by
      their adhesion to relatively thin (about 15 MU) filaments, which excludes large
      old cells. 

PMID- 24913580
TI  - Role of receptors to fibroblast growth factor (FGF) on mesenchymal precursor
      cells in the realization of regenerative effects of alkaloid songorine.
AB  - We studied the mechanisms of regenerative (wound healing) effects of songorine
      associated with functional activation of mesenchymal progenitor cells. The key
      role of FGF receptors on these progenitor cells in the stimulation of realization
      of their growth potential under the effect of the alkaloid was demonstrated.
      Under in vitro conditions, the antibodies to FGF receptor abolished the songorine
      induced increase in the number of fibroblast colony-forming units in bone marrow
      cell culture. The intensity of differentiation of mesenchymal precursors remained
      unchanged. 

PMID- 24913582
TI  - Analysis of circulating tumor cells in patients with triple negative breast
      cancer during preoperative chemotherapy.
AB  - The presence of circulating tumor cells in the blood of patients with triple
      negative breast cancer (early and locally advanced cancer) before and after
      preoperative chemotherapy was assessed using expression markers. Before therapy,
      circulating tumor cells were detected in 5 of 13 (38%) patients with early cancer
      and in 7 of 17 (41.2%) patients with locally advanced cancer. After therapy, the
      circulating immune cells were detected in one patient with locally advanced
      cancer, who had no circulating cells before therapy. The tumor was resistant to
      chemotherapy and the disease progressed. The detected circulating tumor cells
      were HER-2-positive, while the primary tumor was HER-2-negative. It was concluded
      that the circulating immune cells can be a potential marker of the efficiency of
      therapy and predictors of the disease course, while their phenotype can differ
      from the phenotype of the primary tumor. 

PMID- 24913583
TI  - Analysis of the effects of blue light on morphofunctional status of in vitro
      cultured blastocysts from mice carrying gene of enhanced green fluorescent
      protein (EGFP).
AB  - We studied the effect of blue light (440-490 nm) on the development of late
      blastocysts of mice carrying the gene of enhanced green fluorescent protein
      (EGFP). Exposure to blue light for 20 min reduced adhesive properties of
      blastocysts and their capacity to form primary colonies consisting of the cells
      of inner cell mass, trophoblast, and extraembryonic endoderm. The negative
      effects of blue light manifested in morphological changes in the primary colonies
      and impairment of differentiation and migration of cells of the trophoblast and
      extraembryonic endoderm. The problems of cell-cell interaction and inductive
      influences of the inner cell mass on other cell subpopulations are discussed.
      EGFP blastocysts were proposed as the model for evaluation of the mechanisms
      underlying the effects of blue light as the major negative factor of visible
      light used in in vitro experiments on mammalian embryos. 

PMID- 24913584
TI  - Effect of hypoxia on porphyrin metabolism in bone marrow mesenchymal stem cells.
AB  - Under hypoxic conditions, aminolevulinic acid-induced accumulation of porphyrin
      pigments and increase in heme content was observed in bone marrow mesenchymal
      stem cells. The expression of transferrin receptor CD71 responsible for Fe(2+)
      transport into the cell was also enhanced. Blockade of porphyrin-transporting
      protein ABCG2 with fumitremorgin C under conditions of normoxia and hypoxia
      induced accumulation of porphyrin pigments; in hypoxia, these changes were more
      pronounced.

PMID- 24913585
TI  - Analysis of a bioregulator isolated from rat testes in roller organotypic culture
      of mouse testes in vitro.
AB  - A new bioregulator, a representative of membranotropic homeostatic tissue
      specific bioregulators acting in ultralow doses, was isolated from rat testes. A
      model of roller organotypic culturing of mouse testes was developed and the
      protective effect of the bioregulator was analyzed.

PMID- 24913586
TI  - Early morbidity and mortality of laparoscopic sleeve gastrectomy and gastric
      bypass in the elderly: a NSQIP analysis.
AB  - BACKGROUND: Even though the U.S. population is aging, outcomes of bariatric
      surgery in the elderly are not well defined. Current literature mostly evaluates
      the effects of gastric bypass (RYGB), with paucity of data on sleeve gastrectomy
      (SG). The objective of this study was to assess 30-day morbidity and mortality
      associated with laparoscopic SG in patients aged 65 years and over, in comparison
      to RYGB. METHODS: The National Surgical Quality Improvement Program (NSQIP)
      database was queried for all patients aged 65 and over who underwent laparoscopic
      RYGB and SG between 2010 and 2011. Baseline characteristics and outcomes were
      compared. P value<.05 was considered significant. Odds ratios (OR) with 95%
      confidence interval (CI) were reported when applicable. RESULTS: We identified
      1005 patients. Mean body mass index was 44 +/- 7. SG was performed in 155
      patients (15.4%). The American Society of Anesthesiology physical classification
      of 3 or 4 was similar between the 2 groups (82.6% versus 86.7%, P = .173).
      Diabetes was more frequent in the RYGB group (43.2% versus 55.6%, P = .004). 30
      day mortality (0.6% versus 0.6%, OR 1.1, 95% CI .11-9.49), serious morbidity
      (5.2% versus 5.6%, OR .91, 95% CI .42-0.96), and overall morbidity (9% versus
      9.1%, OR 1.0, 95% CI .55-1.81) were similar. CONCLUSION: In elderly patients
      undergoing laparoscopic bariatric surgery, SG is not associated with
      significantly different 30-day outcomes compared to RYGB. Both procedures are
      followed by acceptably low morbidity and mortality.

PMID- 24913587
TI  - Comment on: Evaluation of gastroesophageal reflux before and after laparoscopic
      sleeve gastrectomy using symptom scoring, scintigraphy and endoscopy.

PMID- 24913588
TI  - Pregnancy outcomes and nutritional indices after 3 types of bariatric surgery
      performed at a single institution.
AB  - BACKGROUND: Nutritional status during pregnancy and the effects of nutritional
      deficiencies on pregnancy outcomes after bariatric surgery is an important issue
      that warrants further study. The objective of this study was to investigate
      pregnancy outcomes and nutritional indices after restrictive and malabsorptive
      procedures. METHODS: We investigated pregnancy outcomes of 113 women who gave
      birth to 150 children after biliopancreatic diversion (BPD), Roux-en-Y gastric
      bypass (RYGB), and sleeve gastrectomy (SG) between June 1994 and December 2011.
      Biochemical indices and pregnancy outcomes were compared among the different
      types of surgery and to overall 20-year hospital data, as well as to 56
      presurgery pregnancies in 36 women of the same group. RESULTS: Anemia was
      observed in 24.2% and 15.6% of pregnancies after BPD and RYGB, respectively.
      Vitamin B12 levels decreased postoperatively in all groups, with no further
      decrease during pregnancy; however, low levels were observed not only after BPD
      (11.7%) and RYGB (15.6%), but also after SG (13.3%). Folic acid levels increased.
      Serum albumin levels decreased in all groups during pregnancy, but
      hypoproteinemia was seen only after BPD. Neonates after BPD had significantly
      lower average birth weight without a higher frequency of low birth weight defined
      as<2500 g. A comparison of neonatal data between babies born before surgery and
      siblings born after surgery (AS) showed that AS newborns had lower average birth
      weight with no significant differences in body length or head circumference and
      no cases of macrosomia. CONCLUSION: Our study showed reasonably good pregnancy
      outcomes in this sample population after all types of bariatric surgery provided
      nutritional supplement guidelines are followed. Closer monitoring is required in
      pregnancies after malabsorptive procedures especially regarding protein
      nutrition.

PMID- 24913589
TI  - Short-term morbidity associated with removal and revision of the laparoscopic
      adjustable gastric band.
AB  - BACKGROUND: Laparoscopic adjustable gastric band (LAGB) insertion is a commonly
      performed bariatric procedure with low associated short-term risk. Given that a
      significant number of patients will require additional revision/removal
      procedures, overall morbidity may be underestimated. The objective of this study
      was to define the 30-day morbidity associated with LAGB removal and revision
      procedures. METHODS: Patients undergoing revision or removal of LAGB were
      identified within The American College of Surgeons National Surgery Quality
      Improvement Program (ACS-NSQIP) participant use file using current procedural
      terminology and ICD-9 coding. Patients having concurrent procedures were
      excluded. Primary outcomes included 30-day morbidity. The rate of complications
      in the removal/revision patients versus primary LAGB insertion was compared. We
      also analyzed trends over time. RESULTS: A total of 3,236 patients underwent LAGB
      removal (n = 1,580), revision (n = 1,111) or port site revision (n = 545) from
      2006-2011. The overall 30-day complication rate was 5.6% (95% confidence interval
      [CI]: 4.8%, 6.4%) and was higher in patients undergoing LAGB removal with a 6.8%
      (95% CI: 5.6%, 8.1%) adverse event rate (2.5% infectious, 2.3% wound, 2.4%
      reoperation). A total of 24,438 patients underwent primary LAGB insertion within
      the data set with a 30-day complication rate of 2.6% (95% CI: 2.4%, 2.8%).
      Patients undergoing LABG removal had a significantly higher complication rate
      than those having primary LAGB insertion with an odds ratio of 2.72 (95% CI:
      2.18, 3.37). The proportion of LAGB revision/removal compared to primary
      placement increased annually over the study period (P for trend<.001).
      CONCLUSION: The 30-day morbidity associated with LAGB revision is significant and
      higher than that associated with primary LAGB insertions. The potential need for
      future procedures and the associated additional morbidity should be considered
      when evaluating LAGB as a treatment option for morbid obesity.

PMID- 24913591
TI  - Rare neurologic complication of bariatric surgery: acute motor axonal neuropathy
      (AMAN), a severe motor axonal form of the Guillain Barre syndrome.

PMID- 24913590
TI  - What variables are associated with successful weight loss outcomes for bariatric
      surgery after 1 year?
AB  - BACKGROUND: Prior evidence indicates that predictors of weight loss outcomes
      after gastric bypass surgery fall within 5 domains: 1) presurgical factors, 2)
      postsurgical psychosocial variables (e.g., support group attendance), 3)
      postsurgical eating patterns, 4) postsurgical physical activity, and 5) follow-up
      at postsurgical clinic. However, little data exist on which specific behavioral
      predictors are most associated with successful outcomes (e.g.,>= 50% excess
      weight loss) when considering the 5 domains simultaneously. The objective of this
      study was to specify the behavioral variables, and their respective cutoff
      points, most associated with successful weight loss outcomes. METHODS: Signal
      detection analysis evaluated associations between 84 pre- and postsurgical
      behavioral variables (within the 5 domains) and successful weight loss at >= 1
      year in 274 postgastric bypass surgery patients. RESULTS: Successful weight loss
      was highest (92.6%) among those reporting dietary adherence of>3 on a 9-point
      scale (median = 5) who grazed no more than once-per-day. Among participants
      reporting dietary adherence<3 and grazing daily or less, success rates more than
      doubled when highest lifetime body mass index was<53.7 kg/m(2). Success rates
      also doubled for participants with dietary adherence = 3 if attending support
      groups. No variables from the physical activity or postsurgical follow-up domains
      were significant, nor were years since surgery. The overall model's sensitivity =
      .62, specificity = .92. CONCLUSIONS: To our knowledge, this is the first study to
      simultaneously consider the relative contribution of behavioral variables within
      5 domains and offer clinicians an assessment algorithm identifying cut-off points
      for behaviors most associated with successful postsurgical weight loss. Such data
      may inform prospective study designs and postsurgical interventions.

PMID- 24913592
TI  - Laparoscopic choledochoduodenostomy as an alternate treatment for common bile
      duct stones after Roux-en-Y gastric bypass.
AB  - BACKGROUND: After Roux-en-Y gastric bypass (RYGB), the new gastrointestinal
      configuration does not permit easy endoscopic access to the biliary system in the
      standard fashion. Common bile duct (CBD) stones have proved to be a challenge for
      both the surgeon and the endoscopist in this setting. We shall review our
      experience with laparoscopic choledochoduodenostomy as a treatment of
      choledocholithiasis after gastric bypass. METHODS: Between January 2000 and July
      2012, 3115 patients underwent RYGB at our institution. Patients were included if
      they had postoperative CBD stones regardless of previous cholecystectomy.
      Treatment modality was laparoscopic choledochoduodenostomy. A retrospective chart
      review of a prospectively collected data was completed, noting the outcomes and
      complications of the procedure. RESULTS: Of 3115 patients, 11 patients were
      included in this study. There were 8 female and 3 male patients with a mean age
      of 50.5 +/- 10.9 (range, 34-66) years. The average time between primary RYGB and
      choledochoduodenostomy was 39.7 +/- 33.8 (range 8-113) months. The average body
      mass index at primary surgery was 48.2 +/- 8.1 (range 38.4-67.4) kg/m(2) and at
      choledochoduodenostomy was 29.5 +/- 6.8 (range 22.7-46.9) kg/m(2). One patient
      had bile leak that was managed with drain. All patients had resolution of
      symptoms at a mean follow-up of 24.8 +/- 26.9 (range 2-84) months. CONCLUSION:
      This small case series suggests that, in experienced hands, laparoscopic
      choledochoduodenostomy is an option for safe and effective treatment of
      choledocholithiasis after gastric bypass.

PMID- 24913593
TI  - Comment on: impact of perioperative management on short-term outcomes following
      sleeve gastrectomy: a 600-patient single-center cohort study.

PMID- 24913594
TI  - Comment on: Feasibility of ecological momentary assessment to characterize
      adolescent postoperative diet and activity patterns following weight loss
      surgery.

PMID- 24913595
TI  - Efficacy and safety of laparoscopic mini gastric bypass. A systematic review.
AB  - BACKGROUND: Laparoscopic mini-gastric bypass (LMGB) is a relatively new bariatric
      procedure; published studies are accumulating in various settings. The objective
      of this study was to summarize the available evidence about the efficacy and
      safety of LMGB. METHODS: A systematic search in the literature was performed ,
      and PubMed and reference lists were scrutinized (end-of-search date: July 15,
      2013). For the assessment of the eligible articles, the Newcastle-Ottawa quality
      assessment scale was used. RESULTS: Ten eligible studies were included in this
      study, reporting data on 4,899 patients. According to all included studies, LMGB
      induced substantial weight and body mass index reduction, as well as substantial
      excess weight loss. Moreover, resolution or improvement in all major associated
      medical illnesses and improvement in overall Gastrointestinal Quality of Life
      Index score were recorded. Major bleeding and anastomotic ulcer were the most
      commonly reported complications. Readmission rate ranged from 0%- 11%, whereas
      the rate of revision operations ranged from .3%- 6%. The latter were conducted
      due to a variety of medical reasons such as inadequate or excessive weight loss,
      malnutrition, and upper gastrointestinal bleeding. Finally, the mortality rate
      ranged between 0% and .5% among primary LMGB procedures. CONCLUSION: LMGB
      represents an effective bariatric procedure; its safety and minimal postoperative
      morbidity seem remarkable. Randomized comparative studies seem mandatory for the
      further evaluation of LMGB.

PMID- 24913596
TI  - Biliopancreatic diversion with duodenal switch after renal transplantation.

PMID- 24913597
TI  - Choledocholithiasis after gastric bypass: a growing problem.

PMID- 24913598
TI  - Cutting-edge analysis of extracellular microparticles using ImageStream(X)
      imaging flow cytometry.
AB  - Interest in extracellular vesicle biology has exploded in the past decade, since
      these microstructures seem endowed with multiple roles, from blood coagulation to
      inter-cellular communication in pathophysiology. In order for microparticle
      research to evolve as a preclinical and clinical tool, accurate quantification of
      microparticle levels is a fundamental requirement, but their size and the
      complexity of sample fluids present major technical challenges. Flow cytometry is
      commonly used, but suffers from low sensitivity and accuracy. Use of Amnis
      ImageStream(X) Mk II imaging flow cytometer afforded accurate analysis of
      calibration beads ranging from 1 MUm to 20 nm; and microparticles, which could be
      observed and quantified in whole blood, platelet-rich and platelet-free plasma
      and in leukocyte supernatants. Another advantage was the minimal sample
      preparation and volume required. Use of this high throughput analyzer allowed
      simultaneous phenotypic definition of the parent cells and offspring
      microparticles along with real time microparticle generation kinetics. With the
      current paucity of reliable techniques for the analysis of microparticles, we
      propose that the ImageStream(X) could be used effectively to advance this
      scientific field.

PMID- 24913599
TI  - Short-term UV-B dose stimulates production of protective metabolites in
      Matricaria chamomilla leaves.
AB  - Physiological response of two cultivars of Matricaria chamomilla plants on UV
      irradiation was studied. The impact of used short-time UV dose was evaluated in
      three time points; 2, 24 and 48 h after irradiation. Used UV irradiation
      immediately resulted in changes in plant oxidative status monitored as increased
      concentration of H2 O2 . Decrease in chlorophyll a and b indicated the impact on
      photosynthetic apparatus. For phenolic secondary metabolites, an increase in
      total soluble phenols and AlCl3 -reactive flavonols was observed. The activity of
      main phenolic enzyme, phenylalanine ammonia-lyase, increased with time after
      irradiation. Significant changes, mainly decreasing trends, in the content of
      free coumarins and their glycosidic precursors were observed. Enhanced
      accumulation in chlorogenic and 1,5-dicaffeoylquinic acid and in (Z)-isoform of
      dicycloethers was detected. From these results, the redirecting precursors of
      coumarin biosynthesis to biosynthesis of substances with higher antioxidative
      potential can be assumed. Different reactions in diploid and tetraploid plants
      were recorded, too. 

PMID- 24913600
TI  - A brief adherence intervention that improved glycemic control: mediation by
      patterns of adherence.
AB  - This study examined whether longitudinal adherence profiles mediated the
      relationship between a brief adherence intervention and glycemic control among
      patients with type 2 diabetes. Adherence was assessed using the Medication Event
      Monitoring System. Longitudinal analysis via growth curve mixture modeling was
      carried out to classify patients according to patterns of adherence to oral
      hypoglycemic agents. Hemoglobin A1c assays were used to measure glycemic control
      as the clinical outcome. Across the whole sample, longitudinal adherence profiles
      mediated 35.2% (13.2, 81.0%) of the effect of a brief adherence intervention on
      glycemic control [from odds ratio (OR) = 8.48, 95% confidence interval (CI)
      (3.24, 22.2) to 4.00, 95% CI (1.34, 11.93)]. Our results suggest that patients in
      the intervention had better glycemic control largely due to their greater
      likelihood of adherence to oral hypoglycemic agents.

PMID- 24913602
TI  - Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem
      syndrome.
AB  - The Hennekam lymphangiectasia-lymphedema syndrome is a genetically heterogeneous
      disorder. It can be caused by mutations in CCBE1 which are found in approximately
      25 % of cases. We used homozygosity mapping and whole-exome sequencing in the
      original HS family with multiple affected individuals in whom no CCBE1 mutation
      had been detected, and identified a homozygous mutation in the FAT4 gene.
      Subsequent targeted mutation analysis of FAT4 in a cohort of 24 CCBE1 mutation
      negative Hennekam syndrome patients identified homozygous or compound
      heterozygous mutations in four additional families. Mutations in FAT4 have been
      previously associated with Van Maldergem syndrome. Detailed clinical comparison
      between van Maldergem syndrome and Hennekam syndrome patients shows that there is
      a substantial overlap in phenotype, especially in facial appearance. We conclude
      that Hennekam syndrome can be caused by mutations in FAT4 and be allelic to Van
      Maldergem syndrome.

PMID- 24913603
TI  - Citrulline induces fatty acid release selectively in visceral adipose tissue from
      old rats.
AB  - SCOPE: During aging, increased visceral adipose tissue (AT) mass may result in
      impaired metabolic status. A citrulline (CIT)-supplemented diet reduces AT mass
      in old rats. We hypothesized that CIT could directly affect fatty acid (FA)
      metabolism in retroperitoneal AT. METHODS AND RESULTS: A 24-h exposure of AT
      explants from old (25 months) rats to 2.5 mM CIT induced a 50% rise in glycerol
      and FA release, which was not observed in explants from young (2 months) animals.
      The phosphorylated form of hormone-sensitive lipase, a key lipolytic enzyme, was
      1.5-fold higher in CIT-treated explants from old and young rats, whereas
      glyceroneogenesis, that provides glycerol-3P requested for FA re-esterification,
      and its key enzyme phosphoenolpyruvate carboxykinase, were down-regulated 40-70%.
      Specifically in young rats, beta-oxidation capacity and gene expressions of
      carnitine palmitoyl transferase 1-b and very long chain acyl-CoA dehydrogenase
      were strongly up-regulated by CIT. In contrast, in old rats, while
      glyceroneogenesis was lower, beta-oxidation was not affected, enabling increased
      FA release. CONCLUSION: Hence, in visceral AT, CIT exerts a specific induction of
      the beta-oxidation capacity in young rats and a selective stimulation of FA
      release in old rats, therefore providing a direct mechanism of CIT action to
      reduce AT mass.

PMID- 24913604
TI  - Characterization of the effect of LPS on dendritic cell subset discrimination in
      spleen.
AB  - The Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is a potent
      inflammatory mediator and a leading cause of bacterial sepsis. While LPS is known
      to activate antigen-presenting cells, here we find that LPS down-regulates
      expression of CD11c and CD11b on splenic dendritic cell subsets, thus confounding
      the ability to identify these subsets following treatment. This has implications
      with regard to tracking the response to LPS in terms of the cell subsets
      involved, and should be considered whenever such studies are undertaken. 

PMID- 24913605
TI  - QMachine: commodity supercomputing in web browsers.
AB  - BACKGROUND: Ongoing advancements in cloud computing provide novel opportunities
      in scientific computing, especially for distributed workflows. Modern web
      browsers can now be used as high-performance workstations for querying,
      processing, and visualizing genomics' "Big Data" from sources like The Cancer
      Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) without
      local software installation or configuration. The design of QMachine (QM) was
      driven by the opportunity to use this pervasive computing model in the context of
      the Web of Linked Data in Biomedicine. RESULTS: QM is an open-sourced, publicly
      available web service that acts as a messaging system for posting tasks and
      retrieving results over HTTP. The illustrative application described here
      distributes the analyses of 20 Streptococcus pneumoniae genomes for shared
      suffixes. Because all analytical and data retrieval tasks are executed by
      volunteer machines, few server resources are required. Any modern web browser can
      submit those tasks and/or volunteer to execute them without installing any extra
      plugins or programs. A client library provides high-level distribution templates
      including MapReduce. This stark departure from the current reliance on expensive
      server hardware running "download and install" software has already gathered
      substantial community interest, as QM received more than 2.2 million API calls
      from 87 countries in 12 months. CONCLUSIONS: QM was found adequate to deliver the
      sort of scalable bioinformatics solutions that computation- and data-intensive
      workflows require. Paradoxically, the sandboxed execution of code by web browsers
      was also found to enable them, as compute nodes, to address critical privacy
      concerns that characterize biomedical environments.

PMID- 24913606
TI  - Subcellular localization of calcium in the incompatible and compatible
      interactions of wheat and Puccinia striiformis f. sp. tritici.
AB  - Ca(2+) is an ubiquitous intracellular molecule which is used as a second
      messenger to control many physiological activities in plant cells. In the present
      work, the relationship between calcium localization and the hypersensitive
      response (HR)one of the most crucial and indispensable pathway to resist a
      pathogenwas studied in the wheat-wheat strip rust system using cytochemical
      technique. Our results show that calcium is involved in the interaction between
      wheat and wheat stripe rust. In the incompatible interaction associated with
      necrosis of host mesophyll cells, an influx of Ca(2+) from the intercellular
      space to the cytoplasm and finally an efflux to the intercellular space again was
      detected in an incompatible interaction. Calcium precipitates were also observed
      in mesophyll cells adjacent to necrotic cells. On the contrary, calcium flow was
      not significantly altered in a compatible interaction. These results suggest that
      calcium might induce HR as a secondary messenger in the incompatible interaction
      of wheat and wheat stripe rust.

PMID- 24913607
TI  - Low neonatal blood glucose levels in cesarean-delivered term newborns at Khartoum
      Hospital, Sudan.
AB  - BACKGROUND: Glucose is the main source of energy for organ function in neonates.
      There are few published recent data on neonatal glucose levels during cesarean
      delivery. METHODS: A case (cesarean delivery) -control (vaginal delivery) study
      was conducted at Khartoum Hospital Sudan to compare blood glucose levels of term
      newborns born after elective cesarean delivery with those born vaginally.
      RESULTS: Cord blood glucose levels at delivery were significantly lower in women
      who had a cesarean delivery compared with those who delivered vaginally (99.8 +/-
      20.6 vs. 106.8 +/- 11.1 mg/dl, P=0.026), but there was no significant difference
      (97.8 +/- 16.7 vs. 102.1 +/- 9.6, P=0.110) in newborn glucose levels at 2 hours
      after delivery between the groups. In linear regression, cesarean delivery (
      6.475 mg/dl, P=0.013) and maternal blood glucose levels at the time of delivery
      (+0.619 mg, P<0.001) were significantly associated with mean cord glucose levels.
      CONCLUSION: This study shows that cord blood glucose levels are significantly
      lower in cesarean-delivered neonates than vaginally-delivered neonates. In
      addition, cord blood glucose levels are significantly associated with cesarean
      delivery and maternal blood glucose levels at delivery. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2011479878124993.

PMID- 24913608
TI  - The diagnostic accuracy of the MyDiagnostick to detect atrial fibrillation in
      primary care.
AB  - BACKGROUND: Atrial fibrillation is very common in people aged 65 or older. This
      condition increases the risk of death, congestive heart failure and
      thromboembolic conditions. Many patients with atrial fibrillation are
      asymptomatic and a cerebrovascular accident (CVA) is often the first clinical
      presentation. Guidelines concerning the prevention of CVA recommend monitoring
      the heart rate in patients aged 65 or older. Recently, the MyDiagnostick (Applied
      Biomedical Systems BV, Maastricht, The Netherlands) was introduced as a new
      screening tool which might serve as an alternative for the less accurate pulse
      palpation. This study was designed to explore the diagnostic accuracy of the
      MyDiagnostick for the detection of atrial fibrillation. METHODS: A phase II
      diagnostic accuracy study in a convenience sample of 191 subjects recruited in
      primary care. The majority of participants were patients with a known history of
      atrial fibrillation (n=161). Readings of the MyDiagnostick were compared with
      electrocardiographic recordings. Sensitivity and specificity and their 95%
      confidence interval were calculated using 2x2 tables. RESULTS: A prevalence of
      54% for an atrial fibrillation rhythm was found in the study population at the
      moment of the study. A combination of three measurements with the MyDiagnostick
      for each patient showed a sensitivity of 94% (95% CI 87 - 98) and a specificity
      of 93% (95% CI 85 - 97). CONCLUSION: The MyDiagnostick is an easy-to-use device
      that showed a good diagnostic accuracy with a high sensitivity and specificity
      for atrial fibrillation in a convenience sample in primary care. Future research
      is needed to determine the place of the MyDiagnostick in possible screening or
      case-finding strategies for atrial fibrillation.

PMID- 24913609
TI  - Assessment of occlusion after placement of stainless steel crowns in children - a
      pilot study.
AB  - Many stainless steel crowns (SSCs) disrupt the occlusion in children, but
      stabilisation appears to occur within a short period post-placement. The extent
      and mechanism of these short-term occlusal changes in children are unknown. This
      study sought to determine whether placement of a SSC changes the maximum
      intercuspation position (MIP) in children, whether the MIP returns to normal
      within 4 weeks and whether local anaesthesia had an effect on the child's ability
      to achieve MIP. The T-Scan((r)) III was used for the measurement of occlusal
      contacts. Reliability and reproducibility of the system was determined using a
      calibration exercise where MIP recordings were taken of eleven children not
      undergoing any dental treatment. For the main study, the percentage of total
      occlusal force on each tooth was recorded in 20 children preoperatively, after
      local anaesthesia, after SSC placement and 4 weeks postoperatively. There was no
      significant difference in MIP (P = 0.435) preoperatively and post-administration
      of local anaesthesia. There was a significant difference between the preoperative
      force on a tooth and the reading after crown placement (P = 0.0013, Wilcoxon
      test). By 4 weeks, there was no significant difference overall between post-SSC
      placement and the preoperative value for the tooth (P = 0.3). Administration of
      local anaesthesia did not affect the ability of a child to attain MIP. Maximum
      intercuspation position was disturbed by the placement of a SSC in seven of 20
      cases. When MIP was disturbed, in most cases, it returned to preoperative status
      within 4 weeks of crown placement. 

PMID- 24913611
TI  - Changes in chromatin structure in NIH 3T3 cells induced by valproic acid and
      trichostatin A.
AB  - Valproic acid (VPA) and trichostatin A (TSA) are known histone deacetylase
      inhibitors (HDACIs) with epigenetic activity that affect chromatin supra
      organization, nuclear architecture, and cellular proliferation, particularly in
      tumor cells. In this study, chromatin remodeling with effects extending to
      heterochromatic areas was investigated by image analysis in non-transformed NIH
      3T3 cells treated for different periods with different doses of VPA and TSA under
      conditions that indicated no loss of cell viability. Image analysis revealed
      chromatin decondensation that affected not only euchromatin but also
      heterochromatin, concomitant with a decreased activity of histone deacetylases
      and a general increase in histone H3 acetylation. Heterochromatin protein 1-alpha
      (HP1-alpha), identified immunocytochemically, was depleted from the
      pericentromeric heterochromatin following exposure to both HDACIs. Drastic
      changes affecting cell proliferation and micronucleation but not alteration in
      CCND2 expression and in ratios of Bcl-2/Bax expression and cell death occurred
      following a 48-h exposure of the NIH 3T3 cells particularly in response to higher
      doses of VPA. Our results demonstrated that even low doses of VPA (0.05 mM) and
      TSA (10 ng/ml) treatments for 1 h can affect chromatin structure, including that
      of the heterochromatin areas, in non-transformed cells. HP1-alpha depletion,
      probably related to histone demethylation at H3K9me3, in addition to the effect
      of VPA and TSA on histone H3 acetylation, is induced on NIH 3T3 cells. Despite
      these facts, alterations in cell proliferation and micronucleation, possibly
      depending on mitotic spindle defects, require a longer exposure to higher doses
      of VPA and TSA.

PMID- 24913612
TI  - Hemocompatibility evaluation of small elastomeric hollow fiber membranes as
      vascular substitutes.
AB  - One of the main challenges for clinical implementation of small diameter vascular
      grafts (SDVGs) is their limited hemocompatibility. Important design
      specifications for such grafts include features that minimize the long-term risks
      of restenosis, fouling, and thrombus formation. In our lab, we have developed
      elastomeric hollow fiber membranes (HFMs), using a phase inversion method, as
      candidates for SDVGs. Here, we present our results for in vitro hemocompatibility
      testing of our HFM under flow and static conditions. Our results showed that the
      polymer-based HFMs do not damage the integrity of human red blood cells (RBCs) as
      shown by their low hemolytic extent (less than 2%). When analyzed for blood cell
      lysis using lactate dehydrogenase (LDH) activity as an indicator, no significant
      differences were observed between blood exposed to our HFMs and uncoagulated
      blood. Analysis of protein adsorption showed a low concentration of proteins
      deposited on the surfaces of HFM after 24 h. Platelet adhesion profiles using
      human platelet-rich plasma (PRP) showed that a low level of platelets adhered to
      the HFMs after 24 h, indicating minimal thrombotic potential. Under the majority
      of conditions, no significant differences were observed between medical-grade
      polymers and our HFMs. Eventual optimization of hemocompatible elastomeric HFM
      vessel grafts could lead to improved tissue vascularization as well as
      vascularized, tissue-engineered scaffolds for organ repair. 

PMID- 24913613
TI  - Temporal analysis of dissolution by-products and genotoxic potential of spherical
      zinc-silicate bioglass: "imageable beads" for transarterial embolization.
AB  - Embolization of vascular tumors is an important tool in minimally invasive
      surgical intervention. Radiopaque, non-degradable, and non-deformable spherical
      zinc-silicate glass particles were produced in a range of 45-500 MUm. Three size
      ranges (45-150, 150-300, and 300-500 MUm) were used in the current study. The
      glass microspheres were eluted in polar (saline solution) and non-polar (dimethyl
      sulfoxide) medium, and ion release profiles were recorded using inductively
      coupled plasma atomic emission spectroscopy. Approximately 80% of Gaussian
      distribution was achieved by simple sieving. The ions released from the
      microspheres were dependent upon surface area to volume ratio as well as the
      nature of elution media. Greater ions were released from smaller particles (45
      150 MUm) having largest surface area in polar medium. For the genotoxicity
      bacterial mutation Ames assay, the concentrations of all the ions were well below
      their therapeutic concentration reported in the literature. No mutagenic effect
      was observed in the bacterial mutation Ames test. Hence, it can be concluded that
      the glass microspheres produced herein are non-mutagenic further supporting the
      materials potential as a suitable embolic agent. 

PMID- 24913614
TI  - Assessing cement injection behaviour in cancellous bone: an in vitro study using
      flow models.
AB  - Understanding the cement injection behaviour during vertebroplasty and accurately
      predicting the cement placement within the vertebral body is extremely
      challenging. As there is no standardized methodology, we propose a novel method
      using reproducible and pathologically representative flow models to study the
      influence of cement properties on injection behaviour. The models, confined
      between an upper glass window and a lower aluminium plate, were filled with bone
      marrow substitute and then injected (4, 6 and 8 min after cement mixing) with
      commercially available bone cements (SimplexP, Opacity+, OsteopalV and Parallax)
      at a constant flow rate (3 mL/min). A load cell was used to measure the force
      applied on the syringe plunger and calculate the peak pressure. A camera was used
      to monitor the cement flow during injection and calculate the following
      parameters when the cement had reached the boundary of the models: the time to
      reach the boundary, the filled area and the roundness. The peak pressure was
      comparable to that reported during clinical vertebroplasty and showed a similar
      increase with injection time. The study highlighted the influence of cement
      formulations and model structure on the injection behaviour and showed that
      cements with similar composition/particle size had similar flow behaviour, while
      the introduction of defects reduced the time to reach the boundary, the filled
      area and the roundness. The proposed method provides a novel tool for quick,
      robust differentiation between various cement formulations through the
      visualization and quantitative analysis of the cement spreading at various time
      intervals. 

PMID- 24913615
TI  - A new magnetic nanocapsule containing 5-fluorouracil: in vivo drug release, anti
      tumor, and pro-apoptotic effects on CT26 cells allograft model.
AB  - The purpose of this study was to create an optimized method for preparation of 5
      fluorouracil-loaded magnetic poly lactic-co-glycolic acid nanocapsules and to
      investigate its potential as multifunctional carriers to deliver therapeutic
      agents for tumor-targeted therapies. The in vitro release of the newly
      synthesized 5-fluorouracil-loaded poly lactic-co-glycolic acid magnetic
      nanocapsules was investigated in phosphate-buffered saline medium using the
      dialysis method. In vivo release studies of the magnetic nanocapsules were
      performed in rabbits. Finally, the targeting properties, anti-tumor, and pro
      apoptotic effects of this new magnetic nanocapsule on CT26 cells allograft model
      were studied. The effective diameter of nanocapsules was 67.2 nm. In vivo release
      investigations showed that 5-fluorouracil has a sustained release profile,
      prolonged lifetime in the rabbit plasma, and increased tissue appetency when
      loaded into the magnetic nanocapsule. Magnetic resonance imaging confirmed that
      the magnetic nanocapsules were successfully targeted to the tumor. Additionally,
      the anti-tumor studies revealed that the targeted therapy with magnetic
      nanocapsules containing 5-fluorouracil effectively inhibits the growth of tumors
      compared with 5-fluorouracil alone (P < 0.01). The present study demonstrates
      that this new magnetic nanocapsule can be considered a new nanotechnology-based
      cancer chemotherapy agent in vivo.

PMID- 24913616
TI  - Antimicrobial megaprostheses supported with iodine.
AB  - Deep infection associated with implants remains a serious complication of
      orthopedic surgery. We developed iodine coating for titanium implants. In this
      study, we performed a clinical trial of iodine-coated megaprostheses to evaluate
      its safety and antibacterial effects. Forty-seven patients with malignant bone
      tumor or pyogenic arthritis were treated using iodine-supported titanium
      megaprostheses between July 2008 and May 2013. The mean age was 53.6 years
      (range, 15-85 years). Twenty-six patients were males and 21 were females. The
      diagnoses included malignant bone tumor in 29 cases, infected total knee
      arthroplasty in 11 cases, chronic osteomyelitis due to pyogenic arthritis in six
      cases and loosening of total knee arthroplasty in one case. The iodine-supported
      implants used were 42 Kyocera Limb Salvage System and five KOBELCO K-MAX K-3.
      These megaprostheses were used to prevent infection in 21 patients, treat active
      infections in 26 patients. The mean follow-up period was 30.1 months (range, 8
      50). Infection was prevented in 20 out of 21 patients. Only one patient had
      surgical site infection caused by Pseudomonas aeruginosa and was cured by
      intravenous administration of antibiotics alone without removal of the implant.
      In 26 treatment cases involving one- or two-stage revision surgery, infection
      subsided without any additional surgery. In all cases, there were no signs of
      infection at the time of the last follow-up. White blood cell and C-reactive
      protein levels returned to normal within four weeks after surgery. To confirm
      systemic effects of iodine, thyroid hormone levels in the blood were examined.
      Abnormalities of thyroid gland function were not detected. Loosening of the
      implants was not observed. Excellent bone ingrowth and ongrowth were found around
      iodine-supported megaprostheses. The iodine-supported titanium megaprostheses are
      highly effective and show promise for the prevention and treatment of infections
      in large bone defects. No cytotoxicity or adverse effects were detected with this
      treatment. 

PMID- 24913617
TI  - Robustness evaluation of heart rate variability measures for age gender related
      autonomic changes in healthy volunteers.
AB  - To analyze motion artifact's affect on HRV measures, the age/gender related
      autonomic changes were investigated by using different HRV measures from wearable
      medical devices under ambulatory home-monitoring condition. Twelve healthy
      undergraduates and 20 healthy elderly subjects participated in the research. The
      electrocardiogram data was collected by using waist-worn device developed by us.
      Ten HRV measures were used to analyze the age-related automatic change including
      linear and nonlinear HRV indexes. Many linear HRV indexes were seriously
      contaminated by motion artefact, and did not reflect the age-related autonomic
      change. The approximate entropy (p < 0.001) was the best indicator among 10 HRV
      indexes. However, the approximate entropy was also contaminated by motion
      artefact and did not reflect the gender-related autonomic change. The study
      verified the hypothesis that the HRV measures could be contaminated under
      ambulatory monitoring condition. It is importance for ambulatory home-monitoring
      to study the robustness of HRV measures. 

PMID- 24913618
TI  - Spreading depolarization may link migraine and stroke.
AB  - Migraine increases the risk of stroke, particularly in young and otherwise
      healthy adults. Being the most frequent neurological condition, migraine
      prevalence is on a par with that of other common stroke risk factors, such as
      diabetes or hypertension. Several patterns of association have emerged: (1)
      migraine and stroke share a common association (eg, vasculopathies, patent
      foramen ovale, or pulmonary A-V malformations); (2) injury to the arterial wall
      such as acute arterial dissections can present as migraine aura attacks or
      stroke; (3) strokes rarely develop during a migraine attack, as described for
      "migrainous stroke." Increasing experimental evidence suggests that cerebral
      hyperexcitability and enhanced susceptibility to spreading depolarization, the
      electrophysiologic event underlying migraine, may serve as a mechanism underlying
      the migraine-stroke association. Mice carrying human vascular or neuronal
      migraine mutations exhibit an enhanced susceptibility to spreading depolarization
      while being particularly vulnerable to cerebral ischemia. The severe stroke
      phenotype in migraine mutant mice can be prevented by suppressing spreading
      depolarization. If confirmed in the clinical setting, inhibiting spreading
      depolarization might protect migraineurs at stroke risk as well as decrease
      attacks of migraine. 

PMID- 24913619
TI  - The impact of orthodontic treatment on the quality of life a systematic review.
AB  - BACKGROUND: Although a great number of specific quality of life measures have
      been developed to analyze the impact of wearing fixed appliances, there is still
      a paucity of systematic appraisal of the consequences of orthodontics on quality
      of life. To assess the current evidence of the relationship between orthodontic
      treatment and quality of life. METHODS: Four electronic databases were searched
      for articles concerning the impact of orthodontic treatment on quality of life
      published between January 1960 and December 2013. Electronic searches were
      supplemented by manual searches and reference linkages. Eligible literature was
      reviewed and assessed by methodologic quality as well as by analytic results.
      RESULTS: From 204 reviewed articles, 11 met the inclusion criteria and used
      standardized health related quality of life and orthodontic assessment measures.
      The majority of studies (7/11) were conducted among child/adolescent populations.
      Eight of the papers were categorized as level 1 or 2 evidence based on the
      criteria of the Oxford Centre for Evidence-Based Medicine. An observed
      association between quality of life and orthodontic treatment was generally
      detected irrespective of how they were assessed. However, the strength of the
      association could be described as modest at best. Key findings and future
      research considerations are described in the review. CONCLUSIONS: Findings of
      this review suggest that there is an association (albeit modest) between
      orthodontic treatment and quality of life. There is a need for further studies of
      their relationship, particularly studies that employ standardized assessment
      methods so that outcomes are uniform and thus amenable to meta-analysis.

PMID- 24913621
TI  - Fast plasmonic laser nanowelding for a Cu-nanowire percolation network for
      flexible transparent conductors and stretchable electronics.
AB  - A facile fast laser nanoscale welding process uses the plasmonic effect at a
      nanowire (NW) junction to suppress oxidation and successfully fabricate a Cu-NW
      based percolation-network conductor. The "nanowelding" process does not require
      an inert or vacuum environment. Due to the low-temperature and fast-process
      nature, plasmonic laser nanowelding may form Cu-nanowire networks on heat
      sensitive, flexible or even stretchable substrates. 

PMID- 24913620
TI  - Antagonism of cannabinoid receptor 2 pathway suppresses IL-6-induced
      immunoglobulin IgM secretion.
AB  - BACKGROUND: Cannabinoid receptor 2 (CB2) is expressed predominantly in the immune
      system, particularly in plasma cells, raising the possibility that targeting the
      CB2 pathway could yield an immunomodulatory effect. Although the role of CB2 in
      mediating immunoglobulin class switching has been reported, the effects of
      targeting the CB2 pathway on immunoglobulin secretion per se remain unclear.
      METHODS: Human B cell line SKW 6.4, which is capable of differentiating into IgM
      secreting cells once treated with human IL-6, was employed as the cell model. SKW
      6.4 cells were incubated for 4 days with CB2 ligands plus IL-6 (100 U/ml). The
      amount of secreted IgM was determined by an ELISA. Cell proliferation was
      determined by the 3H-Thymidine incorporation assay. Signal molecules involved in
      the modulation of IgM secretion were examined by real-time RT-PCR and Western
      blot analyses or by using their specific inhibitors. RESULTS: We demonstrated
      that CB2 inverse agonists SR144528 and AM630, but not CB2 agonist HU308 or CB1
      antagonist SR141716, effectively inhibited IL-6-induced secretion of soluble IgM
      without affecting cell proliferation as measured by thymidine uptake. SR144528
      alone had no effects on the basal levels of IgM in the resting cells. These
      effects were receptor mediated, as pretreatment with CB2 agonist abrogated
      SR144528-mediated inhibition of IL-6 stimulated IgM secretion. Transcription
      factors relevant to B cell differentiation, Bcl-6 and PAX5, as well as the
      protein kinase STAT3 pathway were involved in the inhibition of IL-6-induced IgM
      by SR144528. CONCLUSIONS: These results uncover a novel function of CB2
      antagonists and suggest that CB2 ligands may be potential modulators of
      immunoglobulin secretion.

PMID- 24913622
TI  - NMR as evaluation strategy for cellular uptake of nanoparticles.
AB  - Advanced nanostructured materials, such as gold nanoparticles, magnetic
      nanoparticles, and multifunctional materials, are nowadays used in many state-of
      the-art biomedical application. However, although the engineering in this field
      is very advanced, there remain some fundamental problems involving the
      interaction mechanisms between nanostructures and cells or tissues. Here we show
      the potential of (1)H NMR in the investigation of the uptake of two different
      kinds of nanostructures, that is, maghemite and gold nanoparticles, and of a
      chemotherapy drug (Temozolomide) in glioblastoma tumor cells. The proposed
      experimental protocol provides a new way to investigate the general problem of
      cellular uptake for a variety of biocompatible nanostructures and drugs. 

PMID- 24913623
TI  - The effect of patient age on the success of laryngeal reinnervation.
AB  - The objective of the study was to investigate the influence of patient age on the
      efficacy of laryngeal reinnervation with ansa cervicalis in unilateral vocal fold
      paralysis (UVFP) patients. We retrospectively reviewed 349 consecutive UVFP cases
      of laryngeal reinnervation with ansa cervicalis to the recurrent laryngeal nerve
      anastomosis. Preoperative and postoperative videostroboscopy, perceptual
      evaluation, acoustic analysis, maximum phonation time (MPT) and laryngeal
      electromyography (EMG) data were collected. Gender, age, preoperative EMG status
      [preoperative voluntary motor unit recruitment (VMUR)] and denervation duration
      were analyzed in previous multivariable logistic regression analysis.
      Stratification analysis was performed on patient age in the present study. All
      patients were divided into four groups according to their age: Group A included
      patients with an age less than 30 years; Group B, 30-44 years; Group C, 45-59
      years; Group D, >=60 years. Stratification analysis on patient age showed
      significant differences between Group A and D, Group B and D, Group C and D (P <
      0.05), but no significant difference between Group A and B, Group A and C, Group
      B and C (P > 0.05), respectively, with regard to parameters including glottal
      closure, overall grade, shimmer, noise-to-harmonics ratio; but there are no
      significant differences among the four groups with regard to jitter. However, for
      MPT and postoperative VMUR, there are significant differences among the four
      groups expect between Group A and B. In addition, glottal closure, perceptual and
      acoustic parameters, MPT values and VMUR data, were significantly improved
      postoperatively in each age group (P < 0.01). The data from this study indicate
      that patient age is an influential factor of the surgical outcome of laryngeal
      reinnervation for UVFP patients. Laryngeal reinnervation is less effective when
      patient age is more than 60 years.

PMID- 24913624
TI  - Preservation of laryngeal function improves outcomes of patients with
      hypopharyngeal carcinoma.
AB  - This study compares clinical characteristics and survival between patients with
      and without laryngeal function (LF) preservation during surgical treatment for
      hypopharyngeal carcinoma. We retrospectively reviewed 485 cases of hypopharyngeal
      carcinoma treated at a single institution for analysis. There were 337 cases with
      and 148 cases without LF preservation after surgery. Preservation of LF was
      complete in 237 patients and partial in 100 patients. There were significant
      statistical differences between the preservation group and the group without
      preservation in T-stage (P < 0.001), overall staging (P < 0.001), and tumor sites
      (P < 0.001) except the N-stage (P = 0.240). The patients with LF preservation had
      significantly better overall survival (log-rank, P = 0.005) and a lower risk of
      death than those without LF preservation (HR 0.62, 95% CI 0.43-0.97), after
      multivariable adjustment. Treatment with surgery in combination with radiotherapy
      is still the favorable choice for patients with hypopharyngeal carcinoma. The
      maximal restoration of pharyngoesophageal continuity and function improves
      survival for patients whose tumors are excised completely for the preservation of
      LF and laryngeal and pharyngeal reconstruction.

PMID- 24913625
TI  - Complex phylogeny and gene expression patterns of members of the NITRATE
      TRANSPORTER 1/PEPTIDE TRANSPORTER family (NPF) in wheat.
AB  - NPF (formerly referred to as low-affinity NRT1) and 'high-affinity' NRT2 nitrate
      transporter genes are involved in nitrate uptake by the root, and transport and
      distribution of nitrate within the plant. The NPF gene family consists of 53
      members in Arabidopsis thaliana, however only 11 of these have been functionally
      characterized. Although homologous genes have been identified in genomes of
      different plant species including some cereals, there is little information
      available for wheat (Triticum aestivum). Sixteen genes were identified in wheat
      homologous to characterized Arabidopsis low-affinity nitrate transporter NPF
      genes, suggesting a complex wheat NPF gene family. The regulation of wheat NFP
      genes by plant N-status indicated involvement of these transporters in substrate
      transport in relation to N-metabolism. The complex expression pattern in relation
      to tissue specificity, nitrate availability and senescence may be associated with
      the complex growth patterns of wheat depending on sink/source demands, as well as
      remobilization during grain filling. 

PMID- 24913626
TI  - Microarray analysis of laser-microdissected tissues indicates the biosynthesis of
      suberin in the outer part of roots during formation of a barrier to radial oxygen
      loss in rice (Oryza sativa).
AB  - Internal aeration is crucial for root growth in waterlogged soil. A barrier to
      radial oxygen loss (ROL) can enhance long-distance oxygen transport via the
      aerenchyma to the root tip; a higher oxygen concentration at the apex enables
      root growth into anoxic soil. The ROL barrier is formed within the outer part of
      roots (OPR). Suberin and/or lignin deposited in cell walls are thought to
      contribute to the barrier, but it is unclear which compound is the main
      constituent. This study describes gene expression profiles during ROL barrier
      formation in rice roots to determine the relative responses of suberin and/or
      lignin biosyntheses for the barrier. OPR tissues were isolated by laser
      microdissection and their transcripts were analysed by microarray. A total of 128
      genes were significantly up- or downregulated in the OPR during the barrier
      formation. Genes associated with suberin biosynthesis were strongly upregulated,
      whereas genes associated with lignin biosynthesis were not. By an ab initio
      analysis of the promoters of the upregulated genes, the putative cis-elements
      that could be associated with transcription factors, WRKY, AP2/ERF, NAC, bZIP,
      MYB, CBT/DREB, and MADS, were elucidated. They were particularly associated with
      the expression of transcription factor genes containing WRKY, AP2, and MYB
      domains. A semiquantitative reverse-transcription PCR analysis of genes
      associated with suberin biosynthesis (WRKY, CYP, and GPAT) confirmed that they
      were highly expressed during ROL barrier formation. Overall, these results
      suggest that suberin is a major constituent of the ROL barrier in roots of rice. 

PMID- 24913627
TI  - Multiple isoforms of phosphoenolpyruvate carboxylase in the Orchidaceae (subtribe
      Oncidiinae): implications for the evolution of crassulacean acid metabolism.
AB  - Phosphoenolpyruvate carboxylase (PEPC) catalyses the initial fixation of
      atmospheric CO2 into oxaloacetate and subsequently malate. Nocturnal accumulation
      of malic acid within the vacuole of photosynthetic cells is a typical feature of
      plants that perform crassulacean acid metabolism (CAM). PEPC is a ubiquitous
      plant enzyme encoded by a small gene family, and each member encodes an isoform
      with specialized function. CAM-specific PEPC isoforms probably evolved from
      ancestral non-photosynthetic isoforms by gene duplication events and subsequent
      acquisition of transcriptional control elements that mediate increased leaf
      specific or photosynthetic-tissue-specific mRNA expression. To understand the
      patterns of functional diversification related to the expression of CAM, ppc gene
      families and photosynthetic patterns were characterized in 11 closely related
      orchid species from the subtribe Oncidiinae with a range of photosynthetic
      pathways from C3 photosynthesis (Oncidium cheirophorum, Oncidium maduroi,
      Rossioglossum krameri, and Oncidium sotoanum) to weak CAM (Oncidium panamense,
      Oncidium sphacelatum, Gomesa flexuosa and Rossioglossum insleayi) and strong CAM
      (Rossioglossum ampliatum, Trichocentrum nanum, and Trichocentrum carthagenense).
      Phylogenetic analysis revealed the existence of two main ppc lineages in
      flowering plants, two main ppc lineages within the eudicots, and three ppc
      lineages within the Orchidaceae. Our results indicate that ppc gene family
      expansion within the Orchidaceae is likely to be the result of gene duplication
      events followed by adaptive sequence divergence. CAM-associated PEPC isoforms in
      the Orchidaceae probably evolved from several independent origins. 

PMID- 24913628
TI  - 2,4-Dichlorophenoxyacetic acid promotes S-nitrosylation and oxidation of actin
      affecting cytoskeleton and peroxisomal dynamics.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) is a synthetic auxin used as a herbicide
      to control weeds in agriculture. A high concentration of 2,4-D promotes leaf
      epinasty and cell death. In this work, the molecular mechanisms involved in the
      toxicity of this herbicide are studied by analysing in Arabidopsis plants the
      accumulation of reactive oxygen species (ROS) and nitric oxide (NO), and their
      effect on cytoskeleton structure and peroxisome dynamics. 2,4-D (23 mM) promotes
      leaf epinasty, whereas this process was prevented by EDTA, which can reduce .OH
      accumulation. The analysis of ROS accumulation by confocal microscopy showed a
      2,4-D-dependent increase in both H2O2 and O2.(-), whereas total NO was not
      affected by the treatment. The herbicide promotes disturbances on the actin
      cytoskeleton structure as a result of post-translational modification of actin by
      oxidation and S-nitrosylation, which could disturb actin polymerization, as
      suggested by the reduction of the F-actin/G-actin ratio. These effects were
      reduced by EDTA, and the reduction of ROS production in Arabidopsis mutants
      deficient in xanthine dehydrogenase (Atxdh) gave rise to a reduction in actin
      oxidation. Also, 2,4-D alters the dynamics of the peroxisome, slowing the speed
      and shortening the distances by which these organelles are displaced. It is
      concluded that 2,4-D promotes oxidative and nitrosative stress, causing
      disturbances in the actin cytoskeleton, thereby affecting the dynamics of
      peroxisomes and some other organelles such as the mitochondria, with xanthine
      dehydrogenase being involved in ROS production under these conditions. These
      structural changes in turn appear to be responsible for the leaf epinasty.

PMID- 24913629
TI  - Barley has two peroxisomal ABC transporters with multiple functions in beta
      oxidation.
AB  - In oilseed plants, peroxisomal beta-oxidation functions not only in lipid
      catabolism but also in jasmonate biosynthesis and metabolism of pro-auxins.
      Subfamily D ATP-binding cassette (ABC) transporters mediate import of beta
      oxidation substrates into the peroxisome, and the Arabidopsis ABCD protein,
      COMATOSE (CTS), is essential for this function. Here, the roles of peroxisomal
      ABCD transporters were investigated in barley, where the main storage compound is
      starch. Barley has two CTS homologues, designated HvABCD1 and HvABCD2, which are
      widely expressed and present in embryo and aleurone tissues during germination.
      Suppression of both genes in barley RNA interference (RNAi) lines indicated roles
      in metabolism of 2,4-dichlorophenoxybutyrate (2,4-DB) and indole butyric acid
      (IBA), jasmonate biosynthesis, and determination of grain size. Transformation of
      the Arabidopsis cts-1 null mutant with HvABCD1 and HvABCD2 confirmed these
      findings. HvABCD2 partially or completely complemented all tested phenotypes of
      cts-1. In contrast, HvABCD1 failed to complement the germination and
      establishment phenotypes of cts-1 but increased the sensitivity of hypocotyls to
      100 MUM IBA and partially complemented the seed size phenotype. HvABCD1 also
      partially complemented the yeast pxa1/pxa2Delta mutant for fatty acid beta
      oxidation. It is concluded that the core biochemical functions of peroxisomal ABC
      transporters are largely conserved between oilseeds and cereals but that their
      physiological roles and importance may differ. 

PMID- 24913630
TI  - The (r)evolution of gene regulatory networks controlling Arabidopsis plant
      reproduction: a two-decade history.
AB  - Successful plant reproduction relies on the perfect orchestration of singular
      processes that culminate in the product of reproduction: the seed. The floral
      transition, floral organ development, and fertilization are well-studied
      processes and the genetic regulation of the various steps is being increasingly
      unveiled. Initially, based predominantly on genetic studies, the regulatory
      pathways were considered to be linear, but recent genome-wide analyses, using
      high-throughput technologies, have begun to reveal a different scenario. Complex
      gene regulatory networks underlie these processes, including transcription
      factors, microRNAs, movable factors, hormones, and chromatin-modifying proteins.
      Here we review recent progress in understanding the networks that control the
      major steps in plant reproduction, showing how new advances in experimental and
      computational technologies have been instrumental. As these recent discoveries
      were obtained using the model species Arabidopsis thaliana, we will restrict this
      review to regulatory networks in this important model species. However, more
      fragmentary information obtained from other species reveals that both the
      developmental processes and the underlying regulatory networks are largely
      conserved, making this review also of interest to those studying other plant
      species. 

PMID- 24913631
TI  - Prediction of early postoperative cerebral hemorrhage in infective endocarditis
      patients using magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the relationship between preoperative magnetic resonance
      imaging (MRI) findings and the occurrence of postoperative intracranial
      hemorrhage (ICH) in infective endocarditis (IE) patients. METHODS: Between 2002
      and 2012, 30 IE patients required surgical intervention. Four patients developed
      and 26 patients did not develop postoperative ICH. All patients underwent
      preoperative brain MRI. The presence of acute brain infarction was detected by
      diffusion-weighted imaging (DWI), and cerebral microbleeds were detected by T2*
      weighted imaging. RESULTS: Two ICH(+) patients died of stroke. Preoperative
      patient characteristics and operative results were not significantly different.
      Regarding MRI findings, the presence of cerebral microbleeds or acute brain
      infarction alone was not significantly different between the two groups (100 vs.
      29.6 %, p = 0.07; 75.0 vs. 38.5 %, p = 0.37, respectively). The concurrent
      presence of cerebral microbleeds and acute brain infarction was significantly
      correlated with the development of major ICH (75 vs. 14.8 %, p = 0.04). In
      multiple logistic regression analyses, the concurrent presence of cerebral
      microbleeds and acute brain infarction on MRI was an independent predictor of
      major postoperative ICH (p = 0.03, odds ratio 16.5, 95 % confidence interval 1.35
      201.3). CONCLUSION: The combination of T2*-weighted MRI and DWI may be useful to
      evaluate the risk of IE patients developing major postoperative cerebral
      bleeding.

PMID- 24913632
TI  - Therapy for thymic epithelial tumors.
AB  - Thymoma is the most common tumor of the anterior mediastinum. This tumor is
      associated with unique paraneoplastic syndromes. The rarity of this tumor has
      somewhat obscured the optimal treatment for this disease. The World Health
      Organization classification system, which published in 1999, appears to be an
      advance in our understanding of thymoma. The Masaoka classification is now the
      most widely accepted and is an excellent predictor of the prognosis of thymoma.
      Now the International Thymic Malignancy Interest Group is currently engaged in
      the development of a validated formal TNM classification system for thymic
      malignancies. The optimal treatment of thymoma is performed according to its
      clinical stage. Surgery remains the mainstay of treatment for thymic epithelial
      tumors. Minimally invasive surgery including thoracoscopic surgery and robotic
      surgery for stage I and II thymomas is increasing now. The value of postoperative
      radiotherapy in completely resected stage II or III tumors is questionable. As
      thymomas have a moderate response rate to chemotherapy or radiotherapy,
      multimodality therapy involving surgery, chemotherapy and radiotherapy appears to
      increase the rate of complete resection and survival in the advanced (stage III
      and IV) thymomas. 

PMID- 24913633
TI  - Experiences with infectious cDNA clones of equine arteritis virus: lessons
      learned and insights gained.
AB  - The advent of recombinant DNA technology, development of infectious cDNA clones
      of RNA viruses, and reverse genetic technologies have revolutionized how viruses
      are studied. Genetic manipulation of full-length cDNA clones has become an
      especially important and widely used tool to study the biology, pathogenesis, and
      virulence determinants of both positive and negative stranded RNA viruses. The
      first full-length infectious cDNA clone of equine arteritis virus (EAV) was
      developed in 1996 and was also the first full-length infectious cDNA clone
      constructed from a member of the order Nidovirales. This clone was extensively
      used to characterize the molecular biology of EAV and other Nidoviruses. The
      objective of this review is to summarize the characterization of the virulence
      (or attenuation) phenotype of the recombinant viruses derived from several
      infectious cDNA clones of EAV in horses, as well as their application for
      characterization of the molecular basis of viral neutralization, persistence, and
      cellular tropism. 

PMID- 24913634
TI  - Response to Editorial Comment from Dr Sato to Resiniferatoxin for treatment of
      lifelong premature ejaculation: a preliminary study.

PMID- 24913635
TI  - MicroRNA-21 inhibits SMAD7 expression through a target sequence in the 3'
      untranslated region and inhibits proliferation of renal tubular epithelial cells.
AB  - MicroRNAs (miRNAs) are a class of small non-coding single-stranded RNAs that
      regulate gene expression at the posttranscriptional level. Since the
      identification of miRNA, accumulating research has shown their involvement in
      numerous biological processes, including timing of developmental patterning,
      embryogenesis, cell differentiation, organogenesis, growth control and
      pathogenesis of human diseases. It is estimated that >30% human genes may be
      regulated by miRNA, and that each miRNA can regulate >100 target mRNAs. The
      widespread and distinct expression pattern of miRNAs in normal and disease states
      has been extensively investigated in the context of human diseases. Due to the
      diversity of targets, it is challenging to identify the specific target genes and
      elucidate the biological function of a certain miRNAs. In the present study, it
      was confirmed that SMAD7 is a direct target of miR-21, and overexpression of miR
      21 may inhibit the proliferation of rat renal tubular epithelial cells. These
      findings confirm the results of previous studies, which have demonstrated that
      miR-21 regulates the expression of SMAD7 protein. However, further investigation
      is required to determine whether miR-21 is involved in renal development and
      disease, particularly diabetic nephropathy. 

PMID- 24913636
TI  - Ventricular tachycardia associated with ondansetron and phenylephrine
      administration during spinal anaesthesia in pregnancy.

PMID- 24913637
TI  - Safe extubation of a parturient using an airway exchange technique.
AB  - The difficult obstetric airway is a well-recognised anaesthetic challenge but
      little emphasis is placed on the difficulty of performing a safe tracheal
      extubation. We report the use of an airway exchange technique to extubate a
      difficult obstetric airway and discuss the role of these techniques in the
      obstetric population.

PMID- 24913638
TI  - Mixture modelling analysis of one-month disability after stroke: stroke outcomes
      study (SOS1).
AB  - PURPOSE: Understanding the heterogeneity in disability after stroke is important
      to guide treatment and rehabilitation planning. We explored mixture modelling
      analysis to identify subgroups of stroke disability and factors associated with
      disability subgroups. METHOD: Analyses were performed using secondary data from a
      cohort of 448 stroke patients who participated in a 2-year study of stroke
      outcomes. Mixture modelling approach was used to determine subgroups of early
      disability following stroke based on the Barthel Index, General Health
      Questionnaire (GHQ-28), Frenchay Activities Index and the Nottingham Extended
      Activities of Daily Living Scale. RESULTS: Five distinct disability groups were
      identified. Nineteen (4.2%) patients were classified as having very severe
      disability, 58 (12.9%) severe disability, 133 (29.7%) moderate disability, 198
      (44.2%) mild disability and 40 (8.9%) a mood disorder. Compared to the mild
      group, patients in the "very severe" group were more likely to be elderly and to
      have had a previous stroke, and less likely to live alone and had a greater risk
      of mortality 2 years after stroke. Patients in the mood disorder group showed
      greater dependency in activities of daily living were younger compared to the
      other groups and had a greater risk of having mood symptoms 2 years after stroke.
      CONCLUSION: Mixture modelling of 1-month disability after stroke using a broad
      range of outcome measures has identified clinically meaningful groups relating to
      long-term outcomes.

PMID- 24913639
TI  - Emergencies in otolaryngology-head and neck surgery bootcamp: a novel Canadian
      experience.
AB  - OBJECTIVES/HYPOTHESIS: A 1-day intensive course (bootcamp) was developed, to
      teach junior otolaryngology-head and neck surgery (OTO-HNS) residents emergency
      procedural skills, clinical reasoning, and communication skills. This learning
      paradigm utilized a number of novel task trainers, panel discussions, and
      emergency simulations. The study objective was to assess the educational value of
      this bootcamp. STUDY DESIGN: Prospective cohort survey. METHODS: Residents were
      recruited from regional teaching centers within a 2000-km radius of the
      simulation center. Preceptors fluent in English and in French were in attendance.
      Pre-bootcamp outcome measures included the Kolb Learning Style Inventory and a
      self-administered survey measuring confidence levels in performing specific OTO
      HNS tasks. Post-bootcamp outcome measures included a survey evaluating the
      bootcamp experience and a structured follow-up telephone interview. RESULTS:
      Twenty-eight residents participated in the bootcamp from across the United States
      and Canada. When asked if they felt that "overall, the educational day was an
      effective learning process," the average score was 4.75/5.0. The vast majority of
      participants (92.9%) felt they would recommend the bootcamp to a future junior
      resident. Kolb learning styles that prefer active experimentation (acting,
      initiating, and deciding) were more common than those that utilize reflective
      observation (imagining, analyzing, reflecting), which favors a hands-on model of
      learning. CONCLUSION: This first Canadian OTO-HNS bootcamp demonstrated the
      feasibility and effectiveness of conducting a centralized bootcamp for regional
      training centers spanning multiple states/provinces and languages. Future
      bootcamps will be held annually and will ideally continue the natural evolution
      of surgical, hands-on training.

PMID- 24913640
TI  - Interrelations between anthropometric and fitness changes during mid-adolescence
      in boys: a 2-year longitudinal study.
AB  - OBJECTIVES: This study aimed to determine changes and interrelationships between
      changes in selected anthropometric growth parameters and motor and physical
      fitness, among boys over a 2 year period during mid-adolescence. METHODS: Speed,
      agility, hand-eye coordination, explosive power, muscle strength, and aerobic
      endurance were measured once a year, and the anthropometric measurements
      (stature, body mass, sitting height, arm span, and sitting height ratio), were
      measured three times per year, 4 months apart (among 73 adolescent boys). A
      hierarchical linear model, adjusting for covariates and partial correlation
      analysis (R(2) ) were used to analyze the data. RESULTS: All anthropometric,
      motor, and physical measurements improved significantly over the two-year period.
      Significantly, greater changes were seen between 13 and 14 years in stature, arm
      span, sitting height and body mass. Changes in muscle strength, speed and agility
      were mainly significant between 13 and 14 years while the biggest changes
      occurred in explosive power and upper-body-arm-and-shoulder-strength during year
      2 (14-15 years). The majority of interrelationships, indicating moderate to small
      relationships, were found between changes in stature, arm span, and sitting
      height, and changing strength, speed, agility, and hand eye coordination over the
      two-year period, after adjusting for maturity age and physical activity levels.
      CONCLUSION: Motor and physical fitness improved significantly from 13 to 15
      years, showing definite interrelationships with anthropometric growth during the
      mid-adolescence period. Awareness and education about these changes are
      recommended as it can have significant effects on the sport performance and
      fitness training of boys during mid-adolescence.

PMID- 24913641
TI  - Inhibition of the checkpoint kinase Chk1 induces DNA damage and cell death in
      human Leukemia and Lymphoma cells.
AB  - BACKGROUND: Chk1 forms a core component of the DNA damage response and small
      molecule inhibitors are currently being investigated in the clinic as cytotoxic
      chemotherapy potentiators. Recent evidence suggests that Chk1 inhibitors may
      demonstrate significant single agent activity in tumors with specific DNA repair
      defects, a constitutively activated DNA damage response or oncogene induced
      replicative stress. METHODS: Growth inhibition induced by the small molecule Chk1
      inhibitor V158411 was assessed in a panel of human leukemia and lymphoma cell
      lines and compared to cancer cell lines derived from solid tumors. The effects on
      cell cycle and DNA damage response markers were further evaluated. RESULTS:
      Leukemia and lymphoma cell lines were identified as particularly sensitive to the
      Chk1 inhibitor V158411 (mean GI50 0.17 MUM) compared to colon (2.8 MUM) or lung
      (6.9 MUM) cancer cell lines. Chk1 inhibition by V158411 in the leukemia and
      lymphoma cell lines induced DNA fragmentation and cell death that was both
      caspase dependent and independent, and prevented cells undergoing mitosis. An
      analysis of in vitro pharmacodynamic markers identified a dose dependent decrease
      in Chk1 and cyclin B1 protein levels and Cdc2 Thr15 phosphorylation along with a
      concomitant increase in H2AX phosphorylation at Ser139 following V158411
      treatment. CONCLUSIONS: These data support the further evaluation of Chk1
      inhibitors in hematopoietic cancers as single agents as well as in combination
      with standard of care cytotoxic drugs.

PMID- 24913642
TI  - Identification of spermatozoa by tissue-specific differential DNA methylation
      using bisulfite modification and pyrosequencing.
AB  - The focus of this study is to evaluate the application of epigenetic markers as a
      forensic tool for the determination of semen present in sexual assault cases. A
      series of genetic loci were screened in order to identify certain epigenetic
      markers displaying differential methylation that can allow semen to be
      differentiated from blood, buccal cells, skin epidermis, and vaginal epithelial
      cells. Of the different loci tested, a panel of six markers, DACT1, USP49, DDX4,
      Hs_INSL6_03, Hs_ZC3H12D_05, and B_SPTB_03 were identified to contain tissue
      specific differential methylation. Samples ranging from 9-21 for each tissue type
      were collected and subjected to bisulfite modification. The bisulfite modified
      DNA was amplified by PCR, and analyzed by pyrosequencing to quantitate the level
      of methylation at each marker. All six markers successfully differentiated semen
      samples from the other four tissue types analyzed. Sperm DNA was hypomethylated
      in all but one marker, B_SPTB_03, where this marker showed hypermethylation. Mean
      methylation percentages for semen samples were statistically significant from
      mean methylation percentages of the other four tissues studied (p < 0.01). The
      results of this study demonstrate the applicability of epigenetic markers as a
      novel tool for determination of spermatozoa and to identify the tissue source of
      origin of a DNA sample. 

PMID- 24913643
TI  - Evolution of morphological allometry.
AB  - Morphological allometry refers to patterns of covariance between body parts
      resulting from variation in body size. Whether measured during growth
      (ontogenetic allometry), among individuals at similar developmental stage (static
      allometry), or among populations or species (evolutionary allometry), allometric
      relationships are often tight and relatively invariant. Consequently, it has been
      suggested that allometries have low evolvability and could constrain phenotypic
      evolution by forcing evolving species along fixed trajectories. Alternatively,
      allometric relationships may result from natural selection for functional
      optimization. Despite nearly a century of active research, distinguishing between
      these alternatives remains difficult, partly due to wide differences in the
      meaning assigned to the term allometry. In particular, a broad use of the term,
      encompassing any monotonic relationship between body parts, has become common.
      This usage breaks the connection to the proportional growth regulation that
      motivated Huxley's original narrow-sense use of allometry to refer to power-law
      relationships between traits. Focusing on the narrow-sense definition of
      allometry, we review here evidence for and against the allometry-as-a-constraint
      hypothesis. Although the low evolvability and the evolutionary invariance of the
      static allometric slope observed in some studies suggest a possible constraining
      effect of this parameter on phenotypic evolution, the lack of knowledge about
      selection on allometry prevents firm conclusions. 

PMID- 24913644
TI  - Short communication: calf body temperature following chemical disbudding with
      sedation: effects of milk allowance and supplemental heat.
AB  - The use of caustic paste combined with a sedative is one of the least painful
      methods for disbudding. It is recommended to disbud at as early as 5d of age.
      However, the sedative xylazine reportedly causes a decrease in core temperature.
      Furthermore, young calves do not thermoregulate efficiently. We investigated the
      effects of disbudding calves at 5d of age using caustic paste and xylazine
      sedation on body temperature, activity, and milk intake of 46 individually housed
      5-d-old calves in a 2*2 factorial design, with milk fed at 4.5L/d (low-fed
      calves) versus 9L/d (high-fed calves), with or without a heat lamp. Body
      temperature, calf activity (standing time), and barn temperature were monitored
      continuously using automatic data loggers on the day of, before the day of, and
      the day after disbudding. All calves were injected intramuscularly with 0.25mL of
      2mg/mL xylazine 20min before disbudding (dose: 0.12+/-0.003mL/kg of BW). We found
      that the body temperature of 5-d-old calves decreased immediately after the
      injection of the sedative xylazine. The body temperature of calves decreased
      0.9+/-0.09 degrees C and it took 3.8+/-0.32h to climb back to the preinjection
      body temperature. Calves that were fed the lower amount of milk, received a
      higher dose of xylazine (mL/kg BW), or were disbudded in a colder environment
      were more affected by body temperature variations (lower and longest decrease in
      body temperature and higher magnitude). Calf activity recovery followed the
      pattern of body temperature recovery. Milk allowance and supplemental heat did
      not help enhance recovery during the 6h following the procedure. The disbudding
      procedure did not affect milk intake but calves with less body temperature
      decrease or kept in a warmer environment drank more milk following disbudding.
      Low-fed calves were overall more affected by the procedure than high-fed calves
      during the disbudding day and the following day (greater decrease in body
      temperature and drank less in the colder environment). Providing a high-milk diet
      is a suitable option to help mitigate calf discomfort due to the disbudding
      procedure, whereas using a heat lamp does not seem to help, at least in a mildly
      cold winter. 

PMID- 24913645
TI  - The impact of 3 strategies for incorporating polled genetics into a dairy cattle
      breeding program on the overall herd genetic merit.
AB  - Dehorning in cattle has been associated with behavioral, physiological, and
      neuroendocrine responses indicative of pain. Unaddressed, the pain associated
      with a routine production procedure could contribute to a negative public
      perception of livestock production practices. Alternative considerations of
      dehorning include the selection of polled cattle within herds, thereby avoiding
      pain and production loss. As polledness results from an autosomal dominant
      pattern of inheritance, genetic selection for polled cattle could reduce the
      prevalence of the horned trait. Herein we discuss 3 strategies to incorporate
      polled genetics into a cow herd and the estimated impact on the overall genetic
      merit of the herd. Furthermore, the availability and genetic merit of polled
      artificial insemination bulls in the United States is summarized. Both Holstein
      and Jersey dairy bulls registered with the National Association of Animal
      Breeders from December 2010 through April 2013 were queried. Polled bulls were
      identified as either being homozygous (PP) or heterozygous (Pp) and the average
      net merit (NM) predicted transmitting ability (PTA) of each sire group was
      calculated. The percentage of polled calves born each year over a 10-yr period
      was calculated for the following 3 scenarios: (A) various percentages of horned
      cows were randomly mated to Pp bulls, (B) various percentages of horned cows were
      preferentially mated to Pp bulls, and (C) horned cows were selectively mated to
      PP bulls, heterozygous cows to Pp bulls, and homozygous polled cows to horned
      bulls. Additionally, the change in NM PTA of the cow herd was calculated over the
      same period. The highest percentage of polled animals (87%) was achieved in
      scenario C. An evaluation of the herd NM PTA highlights the trade-offs associated
      with increasing polled genetics. Given the current genetic merit of horned and
      polled bulls, increasing the percentage of polled calves will decrease the NM PTA
      in Holstein, but may have minimal impact in Jersey herds. Decisions regarding
      selective breeding to increase polled genetics will need to be evaluated in the
      context of production objectives, cost of dehorning, and impact on overall
      genetic merit. 

PMID- 24913646
TI  - Technical note: a noninvasive method for measuring mammary apoptosis and
      epithelial cell activation in dairy animals using microparticles extracted from
      milk.
AB  - Milk production from dairy animals has been described in terms of 3 processes:
      the increase in secretory cell numbers in late pregnancy and early lactation,
      secretion rate of milk per cell, and the decline in cell numbers as lactation
      progresses. This latter process is thought to be determined by the level of
      programmed cell death (apoptosis) found in the animal. Until now, apoptosis has
      been measured by taking udder biopsies, using magnetic resonance imaging scans,
      or using animals postmortem. This paper describes an alternative, noninvasive
      method for estimating apoptosis by measuring microparticles in milk samples.
      Microparticles are the product of several processes in dairy animals, including
      apoptosis. Milk samples from 12 Holstein cows, at or past peak lactation, were
      collected at 5 monthly samplings. The samples (n=57) were used to measure the
      number of microparticles and calculate microparticle density for 4 metrics:
      annexin V positive and merocyanine 540 dye positive, for both and total
      particles, in both whole milk (WM) and spun milk. Various measures of milk
      production were also recorded for the 12 cows, including daily milk yield, fat
      and protein percentage in the milk, somatic cell count, and the days in milk when
      the samples were taken. A high correlation was found between the 4 WM
      microparticle densities and days in milk (0.46 to 0.64), and a moderate
      correlation between WM microparticle densities and daily milk yield (-0.33 to 
      0.44). No significant relationships were found involving spun milk samples,
      somatic cell count, or fat and protein percentage. General linear model analyses
      revealed differences between cows for both level of microparticle density and its
      rate of change in late lactation. Persistency of lactation was also found to be
      correlated with the WM microparticle traits (-0.65 to -0.32). As apoptosis is
      likely to be the major contributor to microparticle numbers in late lactation,
      this work found a noninvasive method for estimating apoptosis that gave promising
      results. Further investigation is required to find out the factors affecting
      microparticle production and how it changes throughout lactation. 

PMID- 24913647
TI  - Effect of sodium, potassium, magnesium, and calcium salt cations on pH,
      proteolysis, organic acids, and microbial populations during storage of full-fat
      Cheddar cheese.
AB  - Sodium reduction in cheese can assist in reducing overall dietary Na intake, yet
      saltiness is an important aspect of cheese flavor. Our objective was to evaluate
      the effect of partial substitution of Na with K on survival of lactic acid
      bacteria (LAB) and nonstarter LAB (NSLAB), pH, organic acid production, and
      extent of proteolysis as water-soluble nitrogen (WSN) and protein profiles using
      urea-PAGE, in Cheddar cheese during 9mo of storage. Seven Cheddar cheeses with
      molar salt contents equivalent to 1.7% salt but with different ratios of Na, K,
      Ca, and Mg cations were manufactured as well as a low-salt cheese with 0.7% salt.
      The 1.7% salt cheeses had a mean composition of 352g of moisture/kg, 259g of
      protein/kg and 50% fat-on-dry-basis, and 17.5g of salt/kg (measured as Cl(-)).
      After salting, a faster initial decrease in cheese pH occurred with low salt or K
      substitution and it remained lower throughout storage. No difference in intact
      casein levels or percentage WSN levels between the various cheeses was observed,
      with the percentage WSN increasing from 5% at d 1 to 25% at 9mo. A greater
      decrease in intact alphas1-casein than beta-casein was detected, and the ratio of
      alphas1-casein (f121-199) to alphas1-casein could be used as an index of
      ripening. Typical changes in bacteria microflora occurred during storage, with
      lactococci decreasing gradually and NSLAB increasing. Lowering the Na content,
      even with K replacement, extended the crossover time when NSLAB became dominant.
      The crossover time was 4.5mo for the control cheese and was delayed to 5.2, 6.0,
      6.1, and 6.2mo for cheeses with 10, 25, 50, and 75% K substitution. Including 10%
      Mg or Ca, along with 40% K, further increased crossover time, whereas the longest
      crossover time (7.3mo) was for low-salt cheese. By 9mo, NSLAB levels in all
      cheeses had increased from initial levels of <=10(2) to approximately 10(6)cfu/g.
      Lactococci remained at 10(6) cfu/g in the low-salt cheese even after 9mo of
      storage. The propionic acid concentration in the cheese increased when NSLAB
      numbers were high. Few other trends in organic acid concentration were observed
      as a function of Na content. 

PMID- 24913648
TI  - Genetic parameters for rennet- and acid-induced coagulation properties in milk
      from Swedish Red dairy cows.
AB  - Milk coagulation is an important processing trait, being the basis for production
      of both cheese and fermented products. There is interest in including
      technological properties of these products in the breeding goal for dairy cattle.
      The aim of the present study was therefore to estimate genetic parameters for
      milk coagulation properties, including both rennet- and acid-induced coagulation,
      in Swedish Red dairy cattle using genomic relationships. Morning milk samples and
      blood samples were collected from 395 Swedish Red cows that were selected to be
      as genetically unrelated as possible. Using a rheometer, milk samples were
      analyzed for rennet- and acid-induced coagulation properties, including gel
      strength (G'), coagulation time, and yield stress (YS). In addition to the
      technological traits, milk composition was analyzed. A binary trait was created
      to reflect that milk samples that had not coagulated 40min after rennet addition
      were considered noncoagulating milk. The cows were genotyped by using the
      Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers
      remained after quality control and were used to construct a matrix of genomic
      relationships among the cows. Multivariate models including fixed effects of
      herd, lactation stage, and parity were fitted using the ASReml software to obtain
      estimates of heritabilities and genetic and phenotypic correlations. Heritability
      estimates (h(2)) for G' and YS in rennet and acid gels were found to be high
      (h(2)=0.38-0.62) and the genetic correlations between rennet-induced and acid
      induced coagulation properties were weak but favorable, with the exception of
      YSrennet with G'acid and YSacid, both of which were strong. The high heritability
      (h(2)=0.45) for milk coagulating ability expressed as a binary trait suggests
      that noncoagulation could be eliminated through breeding. Additionally, the
      results indicated that the current breeding objective could increase the
      frequency of noncoagulating milk and lead to deterioration of acid-induced
      coagulation through unfavorable genetic associations with protein content (0.38)
      and milk yield (-0.61 to -0.71), respectively. The outcome of this study suggests
      that by including more detailed compositional traits genetically associated with
      milk coagulation or by including milk coagulation properties directly within the
      breeding goal, it appears possible to breed cows that produce milk better suited
      for production of cheese and fermented products. 

PMID- 24913649
TI  - Effects of supplemental progesterone after artificial insemination on expression
      of interferon-stimulated genes and fertility in dairy cows.
AB  - The objectives of the current study were to evaluate the effects of supplemental
      progesterone after artificial insemination (AI) on expression of IFN-stimulated
      genes (ISG) in blood leukocytes and fertility in lactating dairy cows. Weekly
      cohorts of Holstein cows were blocked by parity (575 primiparous and 923
      multiparous) and method of insemination (timed AI or AI on estrus) and allocated
      randomly within each block to untreated controls, a controlled internal drug
      release (CIDR) containing 1.38g of progesterone from d 4 to 18 after AI (CIDR4),
      or a CIDR on d 4 and another on d 7 after AI and both removed on d 18 (CIDR4+7).
      Blood was sampled to quantify progesterone concentrations in plasma and mRNA
      expression in leukocytes for the ubiquitin-like IFN-stimulated gene 15-kDa
      protein (ISG15) and receptor transporter protein-4 (RTP4) genes. Pregnancy was
      diagnosed on d 34+/-3 and 62+/-3 after AI. Treatment increased progesterone
      concentrations between d 5 and 18 after AI in a dose-dependent manner
      (control=3.42, CIDR4=4.97, and CIDR4+7=5.46ng/mL). Cows supplemented with
      progesterone tended to have increased luteolysis by d 19 after AI (control=17.2;
      CIDR4=29.1; CIDR4+7=30.2%), which resulted in a shorter AI interval for those
      reinseminated after study d 18. Pregnancy upregulated expression of ISG in
      leukocytes on d 19 of gestation, but supplementing progesterone did not increase
      mRNA abundance for ISG15 and RTP4 on d 16 after insemination and tended to reduce
      mRNA expression on d 19 after AI. For RTP4 on d 19, the negative effect of
      supplemental progesterone was observed only in the nonpregnant cows. No overall
      effect of treatment was observed on pregnancy per AI on d 62 after insemination
      and averaged 28.6, 32.7, and 29.5% for control, CIDR4, and CIDR4+7, respectively.
      Interestingly, an interaction between level of supplemental progesterone and
      method of AI was observed for pregnancy per AI. For cows receiving exogenous
      progesterone, the lower supplementation with CIDR4 increased pregnancy per AI on
      d 62 in cows inseminated following timed AI (CIDR4=39.2; CIDR4+7=27.5%); in those
      inseminated following detection of estrus, however, the use of a second insert on
      d 7 resulted in greater pregnancy per AI (CIDR4=26.9; CIDR4+7=31.5%). Pregnancy
      loss did not differ among treatments. Supplemental progesterone post-AI using a
      single intravaginal insert on d 4 was beneficial to pregnancy in cows inseminated
      following timed AI, but incremental progesterone with a second insert on d 7 did
      not improve fertility of dairy cows. 

PMID- 24913650
TI  - A mechanistic model for electricity consumption on dairy farms: definition,
      validation, and demonstration.
AB  - Our objective was to define and demonstrate a mechanistic model that enables
      dairy farmers to explore the impact of a technical or managerial innovation on
      electricity consumption, associated CO2 emissions, and electricity costs. We,
      therefore, (1) defined a model for electricity consumption on dairy farms (MECD)
      capable of simulating total electricity consumption along with related CO2
      emissions and electricity costs on dairy farms on a monthly basis; (2) validated
      the MECD using empirical data of 1yr on commercial spring calving, grass-based
      dairy farms with 45, 88, and 195 milking cows; and (3) demonstrated the
      functionality of the model by applying 2 electricity tariffs to the electricity
      consumption data and examining the effect on total dairy farm electricity costs.
      The MECD was developed using a mechanistic modeling approach and required the key
      inputs of milk production, cow number, and details relating to the milk-cooling
      system, milking machine system, water-heating system, lighting systems, water
      pump systems, and the winter housing facilities as well as details relating to
      the management of the farm (e.g., season of calving). Model validation showed an
      overall relative prediction error (RPE) of less than 10% for total electricity
      consumption. More than 87% of the mean square prediction error of total
      electricity consumption was accounted for by random variation. The RPE values of
      the milk-cooling systems, water-heating systems, and milking machine systems were
      less than 20%. The RPE values for automatic scraper systems, lighting systems,
      and water pump systems varied from 18 to 113%, indicating a poor prediction for
      these metrics. However, automatic scrapers, lighting, and water pumps made up
      only 14% of total electricity consumption across all farms, reducing the overall
      impact of these poor predictions. Demonstration of the model showed that total
      farm electricity costs increased by between 29 and 38% by moving from a day and
      night tariff to a flat tariff. 

PMID- 24913651
TI  - Invited review: palmitic and stearic acid metabolism in lactating dairy cows.
AB  - Energy is the most limiting nutritional component in diets for high-producing
      dairy cows. Palmitic (C16:0) and stearic (C18:0) acids have unique and specific
      functions in lactating dairy cows beyond a ubiquitous energy source. This review
      delineates their metabolism and usage in lactating dairy cows from diet to milk
      production. Palmitic acid is the fatty acid (FA) found in the greatest quantity
      in milk fat. Dietary sources of C16:0 generally increase milk fat yield and are
      used as an energy source for milk production and replenishing body weight loss
      during periods of negative energy balance. Stearic acid is the most abundant FA
      available to the dairy cow and is used to a greater extent for milk production
      and energy balance than C16:0. However, C18:0 is also intimately involved in milk
      fat production. Quantifying the transfer of each FA from diet into milk fat is
      complicated by de novo synthesis of C16:0 and desaturation of C18:0 to oleic acid
      in the mammary gland. In addition, incorporation of both FA into milk fat appears
      to be limited by the cow's requirement to maintain fluidity of milk, which
      requires a balance between saturated and unsaturated FA. Oleic acid is the second
      most abundant FA in milk fat and likely the main unsaturated FA involved in
      regulating fluidity of milk. Because the mammary gland can desaturate C18:0 to
      oleic acid, C18:0 appears to have a more prominent role in milk production than
      C16:0. To understand metabolism and utilization of these FA in lactating dairy
      cows, we reviewed production and milk fat synthesis studies. Additional and
      longer lactation studies on feeding both FA to lactating dairy cows are required
      to better delineate their roles in optimizing milk production and milk FA
      composition and yield. 

PMID- 24913652
TI  - Subacute ruminal acidosis challenge changed in situ degradability of feedstuffs
      in dairy goats.
AB  - This study investigated the effects of wheat-induced subacute ruminal acidosis
      (SARA) on rumen bacterial populations and in situ degradabilities of NDF, starch,
      and crude protein of feeds. Four multiparous dairy goats (BW=60+/-3.3kg) fitted
      with ruminal cannulas were assigned to a 2*2 crossover design (28-d treatment
      periods separated by a 7-d washout interval). The treatment diets consisted of 2
      levels of cracked wheat: 0 (control, corn based concentrate) and 35% (diet
      induced SARA, wheat-based concentrate), with a constant forage- (45% alfalfa hay
      and 5% corn silage of DM) to-concentrate (50% of DM) ratio. Results indicate that
      diets with a 35% wheat decreased ruminal pH (6.21 vs. 5.98) and increased the
      duration (1.13 vs. 4.72h/d) and area (0.12 vs. 0.78 pH * h/d) of ruminal pH below
      5.6 and induced SARA. The SARA increased ruminal total volatile fatty acid
      concentration, from 105.0 to 123.8mM, and decreased the acetate molar proportion
      (62.8 vs. 56.6mol/100mol) and the acetate-to-propionate ratio (3.5 vs. 2.8).
      Compared with the control group, SARA decreases the relative abundance of
      Fibrobacter succinogenes (-59.3%) and Ruminococcus flavefaciens (-68.4%), whereas
      it increased Succinimonas amylolytica (198.1%) and Ruminobacter amylophilus
      (125.2%). The SARA decreased 24- and 48-h dry matter (DM) and neutral detergent
      fiber (NDF) degradabilities of corn silage. The 48-h degradabilities of DM (51.0
      vs. 48.2%) and NDF (40.3 vs. 36.0%) in alfalfa hay were not affected by SARA, but
      the SARA tended to reduce the 24-h DM (49.6 vs. 46.3%) and NDF (37.8 vs. 33.2%)
      degradabilities. The effective ruminal degradabilities of DM and NDF in alfalfa
      hay and corn silage were reduced during SARA. In situ degradability parameters of
      DM and starch of wheat were not affected by SARA, but starch degradability of
      corn (9.5 vs. 13.3%/h) increased. The SARA reduced in situ 12-h degradabilities
      of DM and crude protein of soybean meal and extruded soybean without affecting
      the degradabilities of the other protein supplements (corn gluten meal,
      cottonseed meal, corn dried distillers grains with solubles, rapeseed meal, and
      wheat germ meal). These results indicated that the cracked wheat-induced SARA
      reduced the degradation of NDF in roughages and that of protein in soybean meal (
      19.8%) and extruded soy (-18.9%) and increased the starch degradability in corn,
      due to the increased amylolytic bacteria and decreased cellulolytic bacteria
      counts in the rumen. 

PMID- 24913653
TI  - Comparison of emulsifying properties of milk fat globule membrane materials
      isolated from different dairy by-products.
AB  - Emulsifying properties of milk fat globule membrane (MFGM) materials isolated
      from reconstituted buttermilk (BM; i.e., BM-MFGM) and BM whey (i.e., whey-MFGM),
      individually or in mixtures with BM powder (BMP) were compared with those of a
      commercial dairy ingredient (Lacprodan PL-20; Arla Foods Ingredients Group P/S,
      Viby, Denmark), a material rich in milk polar lipids and proteins. The particle
      size distribution, viscosity, interfacial protein, and polar lipids load of oil
      in-water emulsions prepared using soybean oil were examined. Pronounced droplet
      aggregation was observed with emulsions stabilized with whey-MFGM or with a
      mixture of whey-MFGM and BMP. No aggregation was observed for emulsions
      stabilized with BM-MFGM, Lacprodan PL-20, or a mixture of BM-MFGM and BMP. The
      surface protein load and polar lipids load were lowest in emulsions with BM-MFGM.
      The highest protein load and polar lipids load were observed for emulsions made
      with a mixture of whey-MFGM and BMP. The differences in composition of MFGM
      materials, such as in whey proteins, caseins, MFGM-specific proteins, polar
      lipids, minerals, and especially their possible interactions determine their
      emulsifying properties. 

PMID- 24913654
TI  - The effect of probiotics (Lactobacillus rhamnosus HN001, Lactobacillus paracasei
      LPC-37, and Lactobacillus acidophilus NCFM) on the availability of minerals from
      Dutch-type cheese.
AB  - The use of probiotic cultures in the production of Dutch-type cheeses did not
      lead to significant changes in their chemical composition but it lowered their
      acidity. The availability of calcium and magnesium analyzed by in vitro enzymatic
      hydrolysis was 19 and 35%, respectively; the availability of phosphorus was
      significantly higher, at >90%. The use of probiotic cultures significantly
      increased the availability of calcium (~2.5%), phosphorus (~6%), and magnesium
      (~18%). The in vitro method supports accurate determination of the effect of the
      Lactobacillus spp. cultures on the availability of mineral compounds ingested
      with Dutch-type cheese. 

PMID- 24913655
TI  - Double-hit lymphoma mimicking acute lymphoblastic leukemia at presentation.

PMID- 24913656
TI  - Health beliefs and carer burden in first episode psychosis.
AB  - BACKGROUND: Carer burden is high during First Episode Psychosis (FEP) and
      evidence suggests that this is a predictor of poor long-term outcome. However our
      understanding of factors associated with higher burden is poor. We propose that
      carers' cultural backgrounds and health belief models will influence their
      perceived burden of care, over and above that explained by severity of illness.
      METHODS: Patients with FEP and their primary Carers were recruited from the Early
      Intervention Service. Patients and Carers completed a range of validated
      measures, self-report ethnicity and demographic information together with the
      Multidimensional Health Locus of Control and Caregiver Burden Inventory. RESULTS:
      Significant correlations were found between carer burden and health beliefs,
      which differed by ethnicity and gender. High physical burden was experienced by
      Black carers with an external locus of control; time restrictions and emotional
      burden correlated with an external locus of control in Asian carers. For White
      carers, external locus of control correlated with time dependence burden. In all
      ethnic groups female carers experienced more time dependency, physical and
      developmental burden. No significant correlations were found between patient
      measures of severity or duration of illness and carer burden. CONCLUSIONS: The
      type of burden experienced by carers differed between gender and ethnicity and
      was related to their health belief models. Thus the explanation and understanding
      of illness appears to be more salient than simply a patient's severity of illness
      when considering the development of carer burden. Interventions to tackle high
      carer burden, and thus expressed emotion to improve outcome in patients, may need
      increasing focus here.

PMID- 24913657
TI  - Transient Elastography (FibroScan) Is Not Correlated With Liver Fibrosis but With
      Cholestasis in Patients With Long-Term Home Parenteral Nutrition.
AB  - BACKGROUND: Long-term home parenteral nutrition (HPN) may induce liver disorders.
      Transient elastography (TE) has been proposed as a noninvasive alternative to
      liver biopsy analysis for assessment of the progression of hepatic fibrosis to
      cirrhosis. The goal of this study was to compare values from TE measurements to
      biopsy-determined stages of histologic fibrosis in patients receiving HPN.
      METHODS: In this multicenter prospective study, patients receiving long-term HPN
      (>= 6 months) who required a liver biopsy for clinical reasons were included. TE
      (FibroScan) values for each patient were compared with the degree of hepatic
      fibrosis measured from biopsy specimens based on the Brunt classification. TE
      values were also correlated to biochemical and histologic cholestasis. Two
      noninvasive indices for predicting liver fibrosis (APRI and FIB-4) were also
      evaluated. RESULTS: Thirty patients were included in this study (mean age, 42.1
      years; 63% male). The mean duration of HPN was 100.7 months; 25 patients had a
      short bowel and 13 had an intestinal stoma. Biochemical cholestasis was described
      in 22 patients. Liver histologic features varied among these patients. There was
      no correlation between the values of TE and the stages of histologic fibrosis,
      but TE values were significantly correlated to serum bilirubin level and the
      severity of histologic cholestasis as well as APRI and FIB-4 scores. CONCLUSIONS:
      In patients with long-term HPN, TE failed to assess the degree of hepatic
      fibrosis. This could be due to the heterogeneity of liver histologic features
      observed in these patients and the presence of chronic cholestasis.

PMID- 24913658
TI  - Biosimilars: the process is the product. The example of recombinant
      streptokinase.
AB  - BACKGROUND: Worldwide, streptokinase remains the most used thrombolytic agent for
      the treatment of myocardial infarction. Recombinant streptokinase, from E. coli,
      is increasingly used in developing countries as a biosimilar of native
      streptokinase; however, potency assignments relative to the WHO International
      Standard (IS) are highly variable with potentially dangerous consequences. A
      proportion of recombinant streptokinase appears to be incompletely processed,
      retaining the amino-terminal methionine engineered for intracellular expression.
      OBJECTIVES: To investigate and quantify the impact of an amino-terminal
      methionine on streptokinase activity. METHODS: Mature native streptokinase (rSK)
      was cloned and a novel variant constructed to include an amino-terminal
      methionine (rSK-Met) that is not susceptible to processing during expression.
      Potencies of rSK and rSK-Met were determined relative to the WHO IS using a
      chromogenic solution (European Pharmacopoeia) assay, and fibrin-based assays.
      RESULTS: In the chromogenic solution assay there was no measurable difference
      between rSK and rSK-Met activities. In the fibrin-based methods, however, potency
      estimates for rSK-Met were greatly reduced compared with rSK, and fibrinolytic
      activity for rSK-Met was shown to increase over time with methionine
      aminopeptidase treatment. This apparent difference in activity and fibrin
      selectivity was consistent with potency estimates for several different batches
      of commercial recombinant streptokinase products also tested; consequently,
      different potencies would be assigned to therapeutic recombinant streptokinase
      products depending on the degree of amino-terminal methionine processing, and on
      the pharmacopoeial assay method used, affecting the dosage patients receive. This
      has serious health implications and provides an example of the danger in the
      unregulated clinical use of biosimilars.

PMID- 24913659
TI  - Caspases and ROS - dependent mechanism of action mediated by combination of WP
      631 and epothilone B.
AB  - In this article, the synergistic effects of WP 631 and epothilone B (Epo B)
      combination in human ovarian cancer cells (SKOV-3) cells are investigated and the
      reasons for the exact mechanisms of action of both drugs co-administered are
      explained. Compared with single drugs, the combination treatment significantly
      enhances apoptosis as confirmed by increases in caspases (-8, -9, -3) activity,
      ROS level and DNA damage and decreases in mitochondrial membrane potential. The
      combination of the compounds activated both caspase - 8 and -9, indicates that
      both pathways of apoptosis, extrinsic (induced by the effect of Epo B) and
      intrinsic (triggered mainly by WP 631) participate in the proposed treatment.
      Thus, the results of this study strongly suggest a synergistic action of the
      combined treatment with WP 631 and Epo B in SKOV-3 cells death induction. 

PMID- 24913661
TI  - The Breivik controversy: politics, terrorism and psychiatry.
AB  - OBJECTIVES: To examine and analyse the controversy over psychiatric aspects of
      the case of Norwegian far right mass murderer Anders Behring Breivik.
      CONCLUSIONS: Because of a basic acceptance of methodological individualism and
      scientific positivism, mainstream psychiatry is currently ill suited to being
      broadly applied to the spheres of politics and political violence. Rather than
      jettison psychiatric insights in such cases, the choices facing the profession
      are either to accept the narrowness of its utility or to work towards a
      theoretical framework that sees the individual psyche as socially embedded rather
      than as socially constitutive, and psychiatric science itself as socially
      constructed and hence inescapably value-laden.

PMID- 24913660
TI  - Deoxypodophyllotoxin isolated from Juniperus communis induces apoptosis in breast
      cancer cells.
AB  - The study of anticancer properties from natural products has regained popularity
      as natural molecules provide a high diversity of chemical structures with
      specific biological and medicinal activity. Based on a documented library of the
      most common medicinal plants used by the indigenous people of North America, we
      screened and isolated compounds with anti-breast cancer properties from Juniperus
      communis (common Juniper). Using bioassay-guided fractionation of a crude plant
      extract, we identified the diterpene isocupressic acid and the aryltetralin
      lignan deoxypodophyllotoxin (DPT) as potent inducers of caspase-dependent
      programmed cell death (apoptosis) in malignant MB231 breast cancer cells. Further
      elucidation revealed that DPT, in contrast to isocupressic acid, also
      concomitantly inhibited cell survival pathways mediated by the MAPK/ERK and
      NFkappaB signaling pathways within hours of treatment. Our findings emphasize the
      potential and importance of natural product screening for new chemical entities
      with novel anticancer activities. Natural products research complemented with the
      wealth of information available through the ethnobotanical and
      ethnopharmacological knowledge of the indigenous peoples of North America can
      provide new candidate entities with desirable bioactivities to develop new cancer
      therapies. 

PMID- 24913662
TI  - Characterization of the vasa vasorum in the human great saphenous vein: a
      scanning electron microscopy and 3D-morphometry study using vascular corrosion
      casts.
AB  - The vasa vasorum (VV) of explanted segments of the human great saphenous vein
      (Vena saphena magna; HGSV), harvested during dissection for coronary bypass
      grafts or diseased vein segments from the "Salzburger Landesklinikum," were
      studied by scanning electron microscopy and three-dimensional morphometry of
      microvascular corrosion casts. The main objective of this study was to examine
      the VV's structural arrangement in order to find the most vital segments of the
      HGSV and in turn to improve the results of coronary bypass surgeries. The study
      presents a meticulous analysis of the whole microvascular system of the VV of the
      HGSV and its three-dimensional arrangement. It is one of the first studies
      yielding detailed quantitative data on geometry of the VV of the HGSV. A detailed
      insight into different vascular parameters such as vessel diameter,
      interbranching, intervascular distances, and branching angles at different levels
      of the VV's angioarchitecture and in different parts of the HGSV in health and
      disease is given. Further, the geometry of bifurcations was examined in order to
      compute the physiological optimality principles of this delicate vascular system
      based on its construction, maintenance, and function. 

PMID- 24913663
TI  - Empirical fitness landscapes and the predictability of evolution.
AB  - The genotype-fitness map (that is, the fitness landscape) is a key determinant of
      evolution, yet it has mostly been used as a superficial metaphor because we know
      little about its structure. This is now changing, as real fitness landscapes are
      being analysed by constructing genotypes with all possible combinations of small
      sets of mutations observed in phylogenies or in evolution experiments. In turn,
      these first glimpses of empirical fitness landscapes inspire theoretical analyses
      of the predictability of evolution. Here, we review these recent empirical and
      theoretical developments, identify methodological issues and organizing
      principles, and discuss possibilities to develop more realistic fitness landscape
      models. 

PMID- 24913668
TI  - Disease genetics: Mitochondrial variation affects disease risk.

PMID- 24913665
TI  - Transcriptional outcome of telomere signalling.
AB  - Telomeres protect chromosome ends from degradation and inappropriate DNA damage
      response activation through their association with specific factors.
      Interestingly, these telomeric factors are able to localize outside telomeric
      regions, where they can regulate the transcription of genes involved in
      metabolism, immunity and differentiation. These findings delineate a signalling
      pathway by which telomeric changes control the ability of their associated
      factors to regulate transcription. This mechanism is expected to enable a greater
      diversity of cellular responses that are adapted to specific cell types and
      telomeric changes, and may therefore represent a pivotal aspect of development,
      ageing and telomere-mediated diseases. 

PMID- 24913670
TI  - The role of 18F-FDG PET/CT in differentiating malignant from benign portal vein
      thrombosis.
AB  - AIMS: In this retrospective study, we evaluated the role of (18)F
      fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG
      PET/CT) in differentiating malignant from benign portal vein thrombosis (PVT) in
      patients with known malignant tumors. METHODS: Seventy-two patients with
      histologically or clinically confirmed PVT and who had undergone (18)F-FDG PET/CT
      were included. Visual and semiquantitative analyses of PET/CT scans were
      performed. Metabolic activity was measured using the maximum standardized uptake
      value (SUVmax) by drawing the region of interest at the site of thrombosis.
      Receiver operating characteristic analysis was conducted to identify the optimal
      cutoff of SUVmax for detecting neoplastic thrombosis. Malignancy was defined
      using the following criteria: (1) visual analysis and (2) SUVmax >3.35. PET/CT
      results were confirmed with histopathological results and clinical and imaging
      follow-up. RESULTS: The SUVmax of tumor thrombus (6.37 +/- 2.67) was
      significantly higher than that of bland thrombus (2.87 +/- 1.47; P < 0.01). The
      sensitivities, specificities, and accuracies for the two criteria were 91.5 % and
      93.6; 64.0 and 80.0 %; and 81.9 % and 88.9 %, respectively. CONCLUSION: (18)F-FDG
      PET/CT is a promising new method for distinguishing between portal venous
      neoplastic thrombosis and bland thrombosis using semiquantitative analysis, with
      the optimal cutoff value of SUVmax >3.35 as a criterion.

PMID- 24913666
TI  - In pursuit of design principles of regulatory sequences.
AB  - Instructions for when, where and to what level each gene should be expressed are
      encoded within regulatory sequences. The importance of motifs recognized by DNA
      binding regulators has long been known, but their extensive characterization
      afforded by recent technologies only partly accounts for how regulatory
      instructions are encoded in the genome. Here, we review recent advances in our
      understanding of regulatory sequences that influence transcription and go beyond
      the description of motifs. We discuss how understanding different aspects of the
      sequence-encoded regulation can help to unravel the genotype-phenotype
      relationship, which would lead to a more accurate and mechanistic interpretation
      of personal genome sequences. 

PMID- 24913671
TI  - Feasibility of an intervention to enhance preventive care for people with low
      health literacy in primary health care.
AB  - The objective of the study was to explore the feasibility of an intervention that
      enhances preventive care for primary care patients with low health literacy. A
      mixed method study was conducted in four Sydney general practices in areas of
      socioeconomic disadvantage. The intervention included screening for low health
      literacy in patients aged 40-69 years, clinical record audits of care for
      prevention of diabetes and cardiovascular disease, and provider training and
      meetings. Surveys and interviews were conducted to identify providers' approaches
      to, and delivery of, preventive care for people with low health literacy. Our
      study found variable response rates and prevalence of low health literacy. Of the
      eligible patients screened, 29% had low health literacy. Providers described
      three approaches to preventive care, which remained largely unchanged. However,
      they demonstrated recognition of the importance of better communication and
      referral support for patients with low health literacy. Fewer patients with low
      health literacy were identified than expected. Despite improved awareness of the
      need for better communication, there was limited evidence of change in providers'
      approach to providing preventive care, suggesting a need for more attention
      towards providers' attitudes to support these patients.

PMID- 24913673
TI  - Molecular imaging of oral premalignant and malignant lesions using fluorescently
      labeled lectins.
AB  - Aberrant glycosylation during carcinogenesis results in altered glycan expression
      on oral cancer cells. The objective of this study was to detect this atypical
      glycosylation via imaging of fluorophore-conjugated lectins. Paired normal and
      tumor tissue from seven patients with oral squamous cell carcinoma were
      investigated for sialic acid expression via the legume protein wheat germ
      agglutinin (WGA). Fluorophore (Alexa Fluor 350 and Alexa Fluor 647) conjugated
      WGA was topically applied to the tissue samples and imaged using a custom wide
      field fluorescence imaging system. All seven patients had histologically
      confirmed disease with 6/7 exhibiting squamous cell carcinoma and 1/7 exhibiting
      dysplasia. Fluorescent data collected from all patients demonstrated that
      fluorophore conjugated WGA could distinguish between pathologically normal and
      diseased tissue with the average signal-to-noise ratio (SNR) among all patients
      being 5.88 (P = .00046). This SNR was statistically significantly higher than the
      SNR from differences in tissue autofluorescence (P = .0049). A lectin inhibitory
      experiment confirmed that lectin binding is molecularly specific to overexpressed
      tumor glycans and that fluorescence is not due to tissue optical properties or
      tissue diffusion differences. These results illustrate that changes in tumor
      glycan content of oral neoplasms can be detected with optical imaging using
      topically applied fluorescently labeled WGA. Lectin targeting of oral lesions
      using optical imaging may provide a new avenue for the early detection of oral
      cancers. 

PMID- 24913672
TI  - Urokinase-type plasminogen activator deficiency promotes neoplasmatogenesis in
      the colon of mice.
AB  - Urokinase-type plasminogen activator (uPA) participates in cancer-related
      biologic processes, such as wound healing and inflammation. The present study
      aimed to investigate the effect of uPA deficiency on the long-term outcome of
      early life episodes of dextran sodium sulfate (DSS)-induced colitis in mice. Wild
      type (WT) and uPA-deficient (uPA(-/-)) BALB/c mice were treated with DSS or
      remained untreated. Mice were necropsied either 1 week or 7 months after DSS
      treatment. Colon samples were analyzed by histopathology, immunohistochemistry,
      ELISA, and real-time polymerase chain reaction. At 7 months, with no colitis
      evident, half of the uPA(-/-) mice had large colonic polypoid adenomas, whereas
      WT mice did not. One week after DSS treatment, there were typical DSS-induced
      colitis lesions in both WT and uPA(-/-) mice. The affected colon of uPA(-/-)
      mice, however, had features of delayed ulcer re-epithelialization and dysplastic
      lesions of higher grade developing on the basis of a significantly altered
      mucosal inflammatory milieu. The later was characterized by more neutrophils and
      macrophages, less regulatory T cells (Treg), significantly upregulated cytokines,
      including interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha, and IL-10,
      and lower levels of active transforming growth factor-beta1 (TGF-beta1) compared
      to WT mice. Dysfunctional Treg, more robust protumorigenic inflammatory events,
      and an inherited inability to produce adequate amounts of extracellular active
      TGF-beta1 due to uPA deficiency are interlinked as probable explanations for the
      inflammatory-induced neoplasmatogenesis in the colon of uPA(-/-) mice. 

PMID- 24913675
TI  - Clinical Relevance of Increased Endothelial and Mesothelial Expression of
      Proangiogenic Proteases and VEGFA in the Omentum of Patients with Metastatic
      Ovarian High-Grade Serous Carcinoma.
AB  - Epithelial ovarian cancer (EOC) metastasis to the omentum requires implantation
      and angiogenesis. We propose that prometastatic changes in the omental
      endothelium (for angiogenesis) and mesothelium (for implantation) are critical.
      We investigated the expression of angiogenic proteases [cathepsin D (CD),
      cathepsin L (CL), and matrix metalloproteinase 2 (MMP2) and MMP9] and vascular
      endothelial growth factor A (VEGFA) in the mesothelium and endothelium of omentum
      from patients with EOC with omental metastases and control patients with benign
      ovarian tumors. Endothelial expression of CL, VEGFA, and MMP9 and mesothelial
      expression of VEGFA, MMP9, and CD were significantly increased in patients with
      metastasized EOC. High expression of MMP9 and VEGFA in endothelium and
      mesothelium and CD in mesothelium was positively associated with poor disease
      specific survival (DSS). High MMP9 expression in either endothelium or
      mesothelium and presence of ascites prospectively showed the greatest risk of
      shorter DSS [hazard ratio (HR)= 6.16, 95% confidence interval (CI) = 1.76-21.6, P
      = .0045; HR = 11.42, 95% CI = 2.59-50.35, P = .0013; and HR = 6.35, 95% CI = 2.01
      20.1, P = .002, respectively]. High endothelial MMP9 expression and ascites were
      independent predictors of reduced DSS and overall survival, together resulting in
      worst patient prognosis. Our data show that omental metastasis of EOC is
      associated with increased proangiogenic protein expression in the omental
      endothelium and mesothelium. 

PMID- 24913674
TI  - PI3K Inhibition Augments the Therapeutic Efficacy of a 3a-aza
      Cyclopenta[alpha]indene Derivative in Lung Cancer Cells.
AB  - The synergistic targeting of DNA damage and DNA repair is a promising strategy
      for the development of new chemotherapeutic agents for human lung cancer. The DNA
      interstrand cross-linking agent BO-1509, a derivative of 3a-aza
      cyclopenta[alpha]indene, was synthesized and combined with the phosphoinositide 3
      kinase (PI3K) inhibitor LY294002 to treat human lung cancer cells. Our results
      showed that the BO-1509 and LY294002 combination synergistically killed lung
      cancer cells in culture and also suppressed the growth of lung cancer xenografts
      in mice, including those derived from gefitinib-resistant cells. We also found
      that LY294002 suppressed the induction of several DNA repair proteins by BO-1509
      and inhibited the nuclear translocation of Rad51. On the basis of the results of
      the gammaH2AX foci formation assays, LY294002 apparently inhibited the repair of
      DNA damage that was induced by BO-1509. According to the complete blood profile,
      biochemical enzyme analysis, and histopathologic analysis of major organs, no
      apparent toxicity was observed in mice treated with BO-1509 alone or in
      combination with LY294002. Our results suggest that the combination of a DNA
      cross-linking agent with a PI3K inhibitor is a feasible strategy for the
      treatment of patients with lung cancer. 

PMID- 24913676
TI  - Hippo signaling mediates proliferation, invasiveness, and metastatic potential of
      clear cell renal cell carcinoma.
AB  - Recent work has identified dysfunctional Hippo signaling to be involved in
      maintenance and progression of various human cancers, although data on clear cell
      renal cell carcinoma (ccRCC) have been limited. Here, we provide evidence
      implicating aberrant Hippo signaling in ccRCC proliferation, invasiveness, and
      metastatic potential. Nuclear overexpression of the Hippo target Yes-associated
      protein (YAP) was found in a subset of patients with ccRCC. Immunostaining was
      particularly prominent at the tumor margins and highlighted neoplastic cells
      invading the tumor-adjacent stroma. Short hairpin RNA-mediated knockdown of YAP
      significantly inhibited proliferation, migration, and anchorage-independent
      growth of ccRCC cells in soft agar and led to significantly reduced murine
      xenograft growth. Microarray analysis of YAP knockdown versus mock-transduced
      ccRCC cells revealed down-regulation of endothelin 1, endothelin 2, cysteine
      rich, angiogenic inducer, 61 (CYR61), and c-Myc in ccRCC cells as well as up
      regulation of the cell adhesion molecule cadherin 6. Signaling pathway impact
      analysis revealed activation of the p53 signaling and cell cycle pathways as well
      as inhibition of mitogen-activated protein kinase signaling on YAP down
      regulation. Our data suggest CYR61 and c-Myc as well as signaling through the
      endothelin axis as bona fide downstream effectors of YAP and establish aberrant
      Hippo signaling as a potential therapeutic target in ccRCC. 

PMID- 24913677
TI  - Increased accumulation of the cardio-cerebrovascular disease treatment drug
      tanshinone in Salvia miltiorrhiza hairy roots by the enzymes 3-hydroxy-3
      methylglutaryl CoA reductase and 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
AB  - Tanshinone is widely used for treatment of cardio-cerebrovascular diseases with
      increasing demand. Herein, key enzyme genes SmHMGR (3-hydroxy-3-methylglutaryl
      CoA reductase) and SmDXR (1-deoxy-D-xylulose 5-phosphate reductoisomerase)
      involved in the tanshinone biosynthetic pathway were introduced into Salvia
      miltiorrhiza (Sm) hairy roots to enhance tanshinone production. Over-expression
      of SmHMGR or SmDXR in hairy root lines can significantly enhance the yield of
      tanshinone. Transgenic hairy root lines co-expressing HMGR and DXR (HD lines)
      produced evidently higher levels of total tanshinone (TT) compared with the
      control and single gene transformed lines. The highest tanshinone production was
      observed in HD42 with the concentration of 3.25 mg g(-1) DW. Furthermore, the
      transgenic hairy roots showed higher antioxidant activity than control. In
      addition, transgenic hairy root harboring HMGR and DXR (HD42) exhibited higher
      tanshinone content after elicitation by yeast extract and/or Ag(+) than before.
      Tanshinone can be significantly enhanced to 5.858, 6.716, and 4.426 mg g(-1) DW
      by YE, Ag(+), and YE-Ag(+) treatment compared with non-induced HD42,
      respectively. The content of cryptotanshinone and dihydrotanshinone was
      effectively elevated upon elicitor treatments, whereas there was no obvious
      promotion effect for the other two compounds tanshinone I and tanshinone IIA. Our
      results provide a useful strategy to improve tanshinone content as well as other
      natural active products by combination of genetic engineering with elicitors. 

PMID- 24913678
TI  - Bubbles and foams in microfluidics.
AB  - Microfluidics offers great tools to produce highly-controlled dispersions of gas
      into liquid, from isolated bubbles to organized microfoams. Potential
      technological applications are manifold, from novel materials to scaffolds for
      tissue engineering or enhanced oil recovery. More fundamentally, microfluidics
      makes it possible to investigate the physics of complex systems such as foams at
      scales where the capillary forces become dominant, in model experiments involving
      few well-controlled parameters. In this context, this review does not have the
      ambition to detail in a comprehensive manner all the techniques and applications
      involving bubbles and foams in microfluidics. Rather, it focuses on particular
      consequences of working at the microscale, under confinement, and hopes to
      provide insight into the physics of such systems. The first part of this work
      focuses on bubbles, and more precisely on (i) bubble generation, where the
      confinement can suppress capillary instabilities while inertial effects may play
      a role, and (ii) bubble dynamics, paying special attention to the lubrication
      film between bubble and wall and the influence of confinement. The second part
      addresses the formation and dynamics of microfoams, emphasizing structural
      differences from macroscopic foams and the influence of the confinement. 

PMID- 24913679
TI  - MicroRNAs in the diagnosis and prognosis of breast cancer and their therapeutic
      potential (review).
AB  - MicroRNAs (miRNAs) are non-coding single-stranded RNAs in eukaryotes and are
      involved in the regulation of the post-transcriptional expression of specific
      genes. Studies have demonstrated that miRNAs play important roles in regulating
      diverse physiological events such as cell proliferation, differentiation and
      embryo development. In recent decades, considerable attention has been given to
      the relationship between miRNA and the pathology of cancers, particularly breast
      cancer. A large number of miRNAs have been shown to be involved in the
      pathophysiology of breast cancer. Studies have revealed that some miRNAs might
      regulate the oncogenesis and growth of breast cancer by acting on breast tumor
      initiating cells or other downstream targets. Studies have also demonstrated that
      some miRNAs act as suppressors of metastasis or promoters of breast cancer.
      Additionally, certain miRNAs are involved in cancer tissue angiogenesis (one of
      the most important mechanisms of tumor growth and metastasis). Clinical evidence
      indicates that some miRNAs can be used as diagnostic and prognostic biomarkers
      for breast cancer due to their significantly increased or decreased expression in
      cancer tissue. Moreover, certain miRNAs may have therapeutic potential for
      targeting ER-alpha/HER, breast tumor-initiating cells and metastasis as well as
      multidrug resistance. In this review, we discuss the relationship between miRNAs
      and the pathogenesis of breast cancer as well as the progress of current research
      on the miRNA-specific diagnosis, prognosis and treatment of breast cancer.

PMID- 24913680
TI  - The relationship between hepatitis C virus infection and diabetes: time for a
      divorce?

PMID- 24913681
TI  - Human cancer xenografts in outbred nude mice can be confounded by polymorphisms
      in a modifier of tumorigenesis.
AB  - Tumorigenicity studies often employ outbred nude mice, in the absence of direct
      evidence that this mixed genetic background will negatively affect experimental
      outcome. Here we show that outbred nude mice carry two different alleles of
      Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we
      identify previous unreported linked polymorphisms in the promoter, noncoding and
      coding sequences of Pla2g2a and show that outbred nude mice from different
      commercial providers are heterogeneous for this polymorphic Pla2g2a allele. This
      heterogeneity even extends to mice obtained from a single commercial provider,
      which display mixed Pla2g2a genotypes. Notably, we demonstrated that the
      polymorphic Pla2g2a allele affects orthotopic xenograft establishment of human
      colon cancer cells in outbred nude mice. This finding establishes a non-cell
      autonomous role for Pla2g2a in suppressing intestinal tumorigenesis. Using in
      vitro reporter assays and pharmacological inhibitors, we show promoter
      polymorphisms and nonsense-mediated RNA decay (NMD) as underlying mechanisms that
      lead to low Pla2g2a mRNA levels in tumor-sensitive mice. Together, this study
      provides mechanistic insight regarding Pla2g2a polymorphisms and demonstrates a
      non-cell-autonomous role for Pla2g2a in suppressing tumors. Moreover, our direct
      demonstration that mixed genetic backgrounds of outbred nude mice can
      significantly affect baseline tumorigenicity cautions against future use of
      outbred mice for tumor xenograft studies. 

PMID- 24913682
TI  - Corolla is a novel protein that contributes to the architecture of the
      synaptonemal complex of Drosophila.
AB  - In most organisms the synaptonemal complex (SC) connects paired homologs along
      their entire length during much of meiotic prophase. To better understand the
      structure of the SC, we aim to identify its components and to determine how each
      of these components contributes to SC function. Here, we report the
      identification of a novel SC component in Drosophila melanogaster female oocytes,
      which we have named Corolla. Using structured illumination microscopy, we
      demonstrate that Corolla is a component of the central region of the SC.
      Consistent with its localization, we show by yeast two-hybrid analysis that
      Corolla strongly interacts with Cona, a central element protein, demonstrating
      the first direct interaction between two inner-synaptonemal complex proteins in
      Drosophila. These observations help provide a more complete model of SC structure
      and function in Drosophila females.

PMID- 24913683
TI  - A decision aid regarding treatment options for patients with an asymptomatic
      abdominal aortic aneurysm: a randomised clinical trial.
AB  - OBJECTIVE: Abdominal aortic aneurysm patients tend to be informed inconsistently
      and incompletely about their disorder and the treatment options open to them. The
      objective of this trial was to evaluate whether these patients are better
      informed and experience less decisional conflict regarding their treatment
      options after viewing a decision aid. DESIGN: A six-centre, randomised clinical
      trial comparing a decision aid plus regular information versus regular
      information from the surgeon. METHODS: Included patients had recently been
      diagnosed with an asymptomatic abdominal aortic aneurysm at least 4 cm in
      diameter. The decision aid consisted of a one-time viewing of an interactive CD
      ROM elaborating on elective surgery versus watchful waiting. Generally, the
      decision aid advised patients with aneurysms less than 5.5 cm to agree to
      watchful waiting, for larger aneurysms the decision aid provided insight into the
      balance of benefit and harm of surgical and conservative approaches, taking into
      account age, co-morbidity and size of the aneurysm. The primary outcome was
      patient decisional conflict measured at 1 month follow-up (Decisional Conflict
      Scale). Secondary outcomes were patient knowledge, anxiety and satisfaction.
      RESULTS: In 178 aneurysm patients, decisional conflict scores did not differ
      significantly between the decision aid and the regular information groups (22 vs.
      24 on the 0-100 Decisional Conflict Scale; p = .33). Patients in the decision aid
      group had significantly better knowledge (10.0 vs. 9.4 out of 13 points; p =
      .04), whereas anxiety levels (4.4 and 5.0 on a 0-21 scale; p = .73) and
      satisfaction scores (74 and 73 on a 0-100 scale; p = .81) were similar in both
      groups. CONCLUSION: In addition to regular patient-surgeon communication, a
      decision aid helps to share treatment decisions with abdominal aortic aneurysm
      patients by increasing their knowledge about the disorder and available treatment
      options without raising anxiety levels; however, it does not reduce decisional
      conflict, nor does it improve satisfaction.

PMID- 24913684
TI  - Long-term outcomes and sac volume shrinkage after endovascular popliteal artery
      aneurysm repair.
AB  - OBJECTIVES: The aim was to evaluate long-term outcomes and sac volume shrinkage
      after endovascular popliteal artery aneurysm repair (EVPAR). METHODS: This study
      was a retrospective review of all EVPAR cases between 1999 and 2012. Sac volume
      shrinkage, long-term patency, limb salvage, and survival were evaluated using
      Kaplan-Meier estimates. The association of anatomical and clinical
      characteristics with patency was evaluated using multivariate analysis. RESULTS:
      Forty-six EVPAR were carried out in 42 patients (mean age 78 years, 86% male;
      mean sac volume 45.5 +/- 3.5 mL). In 93% of cases (n = 43) the procedure was
      elective, while in 7% of cases it was for rupture (n = 2) or acute thrombosis (n
      = 1). Of the 43 patients who underwent elective repair, 58% were asymptomatic and
      42% symptomatic (14 claudication, 3 rest pain, and 1 compression symptoms).
      Technical success was 98%. Mean duration of follow-up was 56 +/- 21 months.
      Primary patency at 1, 3, and 5 years was 82% (SE 2), 79% (SE 4), and 76% (SE 4),
      while secondary patency was 90% (SE 5), 85% (SE 4), and 82% (SE 1) respectively;
      at 5 years there was 98% limb salvage and an 84% survival rate. During follow-up
      11 limbs had stent graft failure: six required conversion, one underwent
      amputation, and four continued with mild claudication. Of those with graft
      failure, 63% (7/11) occurred within the first year of follow-up. The mean
      aneurysm sac volume shrinkage between preoperative and 5-year post-procedure
      measurement was significant (45.5 +/- 3.5 mL vs. 23.0 +/- 5.0 mL; p < .001).
      Segment coverage >20 cm was a negative predictor for patency (HR 2.76; 95% CI
      0.23; p = .032). CONCLUSIONS: EVPAR provides successful aneurysm exclusion with
      good long-term patency, excellent limb salvage, and survival rates. Close
      surveillance is nevertheless required, particularly during the first
      postoperative year. Patients requiring long segment coverage (>20 cm) may be at
      increased risk for failure.

PMID- 24913685
TI  - Sequence and expression divergence of an ancient duplication of the chaperonin
      groESEL operon in Vibrio species.
AB  - Heat-shock proteins are molecular chaperones essential for protein folding,
      degradation and trafficking. The human pathogen Vibrio vulnificus encodes a copy
      of the groESEL operon in both chromosomes and these genes share <80 % similarity
      with each other. Comparative genomic analysis was used to determine whether this
      duplication is prevalent among Vibrionaceae specifically or Gammaproteobacteria
      in general. Among the Vibrionaceae complete genome sequences in the database (31
      species), seven Vibrio species contained a copy of groESEL in each chromosome,
      including the human pathogens Vibrio cholerae, Vibrio parahaemolyticus and V.
      vulnificus. Phylogenetic analysis of GroEL among the Gammaproteobacteria
      indicated that GroESEL-1 encoded in chromosome I was the ancestral copy and
      GroESEL-2 in chromosome II arose by an ancient gene duplication event.
      Interestingly, outside of the Vibrionaceae within the Gammaproteobacteria,
      groESEL chromosomal duplications were rare among the 296 genomes examined; only
      five additional species contained two or more copies. Examination of the
      expression pattern of groEL from V. vulnificus cells grown under different
      conditions revealed differential expression between the copies. The data
      demonstrate that groEL-1 was more highly expressed during growth in exponential
      phase than groEL-2 and a similar pattern was also found in both V. cholerae and
      V. parahaemolyticus. Overall these data suggest that retention of both copies of
      groESEL in Vibrio species may confer an evolutionary advantage. 

PMID- 24913686
TI  - Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to
      cationic toxic compounds of Candida glabrata.
AB  - Candida glabrata is a salt-tolerant and fluconazole (FLC)-resistant yeast
      species. Here, we analyse the contribution of plasma-membrane alkali-metal-cation
      exporters, a cation/proton antiporter and a cation ATPase to cation homeostasis
      and the maintenance of membrane potential (DeltaPsi). Using a series of single
      and double mutants lacking CNH1 and/or ENA1 genes we show that the inability to
      export potassium and toxic alkali-metal cations leads to a slight
      hyperpolarization of the plasma membrane of C. glabrata cells; this
      hyperpolarization drives more cations into the cells and affects cation
      homeostasis. Surprisingly, a much higher hyperpolarization of C. glabrata plasma
      membrane was produced by incubating cells with subinhibitory concentrations of
      FLC. FLC treatment resulted in a substantially increased sensitivity of cells to
      various cationic drugs and toxic cations that are driven into the cell by
      negative-inside plasma-membrane potential. The effect of the combination of FLC
      plus cationic drug treatment was enhanced by the malfunction of alkali-metal
      cation transporters that contribute to the regulation of membrane potential and
      cation homeostasis. In summary, we show that the combination of subinhibitory
      concentrations of FLC and cationic drugs strongly affects the growth of C.
      glabrata cells. 

PMID- 24913687
TI  - Phenotypic transition of corpus cavernosum smooth muscle cells subjected to
      hypoxia.
AB  - Corpora cavernosum smooth muscle cells (CCSMCs) have been shown to play a
      critical role in the male erectile response and are involved in the pathogenesis
      of multiple causes of erectile dysfunction (ED). To investigate the underlying
      mechanisms, we studied the changes that CCSMCs undergo under hypoxic conditions
      in vitro. The identified and characterized CCSMCs were exposed to hypoxia for 48
      h and its phenotypic changes were examined by light and electron microscopy, MTS
      assay and flow cytometry. The mRNA and protein levels of TGF-beta1 and type I/III
      collagen, as well as CCSMC phenotype marker proteins and their transcriptional
      factors, were assessed by qPCR, immunofluorescence analysis and western blotting.
      Our results showed that CCSMCs became hypertrophic with loss of myofilament
      bundles and formation of an extensive rough endoplasmic reticulum (RER) under
      hypoxic conditions, with inhibited cell proliferation and enhanced cell
      apoptosis. This was accompanied by the increased synthesis of TGF-beta1 and types
      I and III collagen. Moreover, smooth muscle cell phenotypic markers were also
      affected by hypoxic conditions, as indicated by the decrease in alpha-SMA, desmin
      and CNN1 expression and the increase in vimentin expression. These changes
      corresponded to changes in associated transcriptional factors, such as the
      increase in Elk-1 and KLF-4 expression and decrease in Myocd expression. In
      addition, a HIF-1alpha knockdown effectively reversed the hypoxia-induced CCSMC
      phenotype, whereas its overexpression induced the dedifferentiation phenotype.
      These results indicate that CCSMCs undergo a phenotypic transition under hypoxic
      conditions. 

PMID- 24913688
TI  - Composition of a neuromere and its segmental diversification under the control of
      Hox genes in the embryonic CNS of Drosophila.
AB  - Studies performed at the level of single, identified cells in the fruitfly
      Drosophila have decisively contributed to our understanding of the mechanisms
      underlying the development and function of the nervous system. This review
      highlights some of the work based on single-cell analyses in the embryonic/larval
      CNS that sheds light on the principles underlying formation and organization of
      an entire segmental unit and its divergence along the anterior/posterior body
      axis.

PMID- 24913690
TI  - Operative treatment of metacarpal and phalangeal fractures in athletes: early
      return to play.
AB  - BACKGROUND: Evaluating the outcomes of operative treatment for metacarpal and
      phalangeal fractures in athletes returning early to play and discussing the more
      effective methods that permit rapid early return to athletic activity. METHODS:
      We retrospectively identified a total of 105 metacarpal or phalangeal fractures
      in 105 athletes with conservative or operative treatment in our department. Of
      these, 20 athletes required an early return to sport because of a pending
      important game in their competition within 1 month after injury. Therefore, they
      underwent surgical treatment with open reduction and internal fixation of
      metacarpal or phalangeal fractures in an attempt to achieve an early return to
      their chosen sport at their usual competitive level. The patients included 6
      rugby football players, 2 soccer goalkeepers, 3 American football players, 3
      handball players, 2 baseball players and 4 who participated in other sports. The
      clinical records of preoperative and postoperative radiographs were available for
      all patients, and clinical outcome was evaluated by total active motion (TAM).
      RESULTS: The patients were followed up for a mean of 27 (24-43) months. At the
      latest follow-up examination, bone union was obtained in all cases. In cases with
      metacarpal and phalangeal fractures, the average TAM was 263 degrees  (range 240
      degrees -270 degrees ). CONCLUSION: We consider that an early comeback to
      training and competition can be permitted exclusively for patients with
      metacarpal and phalangeal fractures. It is important for the attending physician
      to administer such treatment after obtaining informed consent and develop a
      trusting relationship with the patient and other related individuals while paying
      attention to their hope of quick recovery.

PMID- 24913689
TI  - Insufficient resolution response in the hippocampus of a senescence-accelerated
      mouse model--SAMP8.
AB  - Aging is the primary risk factor for Alzheimer's disease (AD), and it is known
      that inflammation is associated with both aging and AD. To resolve inflammation,
      biosynthesis of the specialized pro-resolving mediators (SPMs) is enhanced in a
      programmed and active manner. We investigated the effect of age on resolution by
      analyzing hippocampal tissue from 2- and 9-month-old senescence-accelerated mouse
      prone 8 (SAMP8), as well as age-matched senescence-accelerated mouse resistant 1
      (SAMR1). Pro-inflammatory markers increased upon age in SAMP8 mice and were also
      higher than those in age-matched SAMR1 mice. However, neither SPMs nor their
      receptors were enhanced upon age in SAMP8 mice compared to age-matched SAMR1
      mice. Analysis of SPM biosynthetic enzymes revealed elevated levels of leukocyte
      type 12-lipoxygenase (L12-LOX) and decreased 5-LOX levels upon age in SAMR1 mice,
      whereas they remained unchanged in SAMP8 mice. Moreover, we found partial co
      localization of L12-LOX and amyloid beta (Abeta) staining, as well as correlation
      between L12-LOX and phosphorylated tau levels in SAMP8, but not SAMR1 mice. Thus,
      we conclude that the resolution response in SAMP8 mice is insufficient to
      counteract the increased inflammation with age, and this may have a role in the
      development of AD-like pathologies. 

PMID- 24913691
TI  - Transcobalamin derived from bovine milk stimulates apical uptake of vitamin B12
      into human intestinal epithelial cells.
AB  - Intestinal uptake of vitamin B12 (hereafter B12) is impaired in a significant
      proportion of the human population. This impairment is due to inherited or
      acquired defects in the expression or function of proteins involved in the
      binding of diet-derived B12 and its uptake into intestinal cells. Bovine milk is
      an abundant source of bioavailable B12 wherein it is complexed with
      transcobalamin. In humans, transcobalamin functions primarily as a circulatory
      protein, which binds B12 following its absorption and delivers it to peripheral
      tissues via its cognate receptor, CD320. In the current study, the transcobalamin
      B12 complex was purified from cows' milk and its ability to stimulate uptake of
      B12 into cultured bovine, mouse and human cell lines was assessed. Bovine milk
      derived transcobalamin-B12 complex was absorbed by all cell types tested,
      suggesting that the uptake mechanism is conserved across species. Furthermore,
      the complex stimulated the uptake of B12 via the apical surface of differentiated
      Caco-2 human intestinal epithelial cells. These findings suggest the presence of
      an alternative transcobalamin-mediated uptake pathway for B12 in the human
      intestine other than that mediated by the gastric glycoprotein, intrinsic factor.
      Our findings highlight the potential for transcobalamin-B12 complex derived from
      bovine milk to be used as a natural bioavailable alternative to orally
      administered free B12 to overcome B12 malabsorption.

PMID- 24913692
TI  - Ongoing clinical trials for Vasovagal Syncope: where are we in 2014?
AB  - Vasovagal Syncope (VVS) can lead to a markedly diminished quality of life for
      some patients. While there are many treatments for this condition including
      physical, mechanical, pharmacologic, and device-based control of heart rate,
      there are few that have been shown to be effective in randomized clinical trials.
      In our local experience, we have achieved significant improvement in symptom
      frequency and quality of life using algorithms based on the data available and on
      clinical acumen for the majority of patients with VVS. Despite this, there are
      still many patients who suffer from treatment refractory VVS. Fortunately, there
      are a number of ongoing clinical trials that are likely to add to our knowledge.
      Ongoing clinical trials are reviewed to examine new treatment methods for VVS
      that were listed on public trial registries as of April 15, 2014. Data from these
      trials should inform future strategies in the care of patients with VVS. 

PMID- 24913693
TI  - Characterisation of nasal Staphylococcus delphini and Staphylococcus
      pseudintermedius isolates from healthy donkeys in Tunisia.
AB  - REASONS FOR PERFORMING STUDY: Staphylococcus intermedius group (SIG) bacteria can
      colonise the nares of some animals but are also emerging pathogens in humans and
      animals. OBJECTIVES: To analyse SIG nasal carriage in healthy donkeys destined
      for food consumption in Tunisia and to characterise recovered isolates. METHODS:
      Nasal swabs from 100 healthy donkeys were tested for SIG recovery, and isolates
      were identified by biochemical and molecular methods. Antimicrobial
      susceptibility of isolates was tested and detection of antimicrobial resistance
      and virulence genes was performed. Isolates were typed at the clonal level by
      multilocus sequence typing and SmaI pulsed-field gel electrophoresis. RESULTS:
      Staphylococcus delphini and Staphylococcus pseudintermedius (included in SIG)
      were obtained in 19% and 2% of the tested samples, respectively, and one isolate
      per sample was characterised. All isolates were meticillin susceptible and mecA
      negative. Most S. delphini and S. pseudintermedius isolates showed susceptibility
      to all antimicrobials tested, with the exception of 2 isolates resistant to
      tetracycline (tet(M) gene) or fusidic acid. The following toxin genes were
      identified (percentage of isolates): lukS-I (100%), lukF-I (9.5%), siet (100%),
      se-int (90%), seccanine (19%) and expA (9.5%). Thirteen different pulsed-field
      gel electrophoresis profiles were identified among the 21 SIG isolates.
      Additionally, the following 9 different sequence types (STs) were detected by
      multilocus sequence typing, 6 of them new: ST219 (6 isolates), ST12 (5 isolates),
      ST220 (3 isolates), ST13, ST50, ST193, ST196, ST218 and ST221 (one isolate each).
      CONCLUSIONS: Staphylococcus delphini and S. pseudintermedius are common nasal
      colonisers of donkeys, generally susceptible to the antimicrobials tested;
      nevertheless, these SIG isolates contain virulence genes, including the recently
      described exfoliative gene (expA) and several enterotoxin genes, with potential
      implications for public health. This is the first description of S. delphini in
      Tunisia. The Summary is available in Chinese - see Supporting information.

PMID- 24913694
TI  - Targeting breast cancer initiating cells: advances in breast cancer research and
      therapy.
AB  - Over the past 10 years there have been significant advances in our understanding
      of breast cancer and the important roles that breast cancer initiating cells
      (CICs) play in the development and resistance of breast cancer. Breast CICs
      endowed with self-renewing and tumor-initiating capacities are believed to be
      responsible for the relapses which often occur after various breast cancer
      therapies. In this review, we will summarize some of the key developments in
      breast CICs which will include discussion of some of the key genes implicated:
      estrogen receptor (ER), HER2, BRCA1, TP53, PIK3CA, RB, P16INK1 and various miRs
      as well some drugs which are showing promise in targeting CICs. In addition, the
      concept of combined therapies will be discussed. Basic and clinical research is
      resulting in novel approaches to improve breast cancer therapy by targeting the
      breast CICs. 

PMID- 24913695
TI  - Evaluation of functional outcomes after laparoscopic partial nephrectomy using
      renal scintigraphy: clamped vs clampless technique.
AB  - OBJECTIVES: To examine differences in postoperative renal functional outcomes
      when comparing clampless with conventional laparoscopic partial nephrectomy (LPN)
      by using renal scintigraphy, and to identify the predictors of poorer
      postoperative renal functional outcomes after clampless LPN. PATIENTS AND
      METHODS: Between September 2010 and September 2012, 87 patients with renal masses
      suitable for LPN were prospectively enrolled in the study. From September 2010 to
      September 2011, LPN with renal artery clamping was performed and from September
      2011 to September 2012 clampless LPN (no clamping of renal artery) was performed.
      Patients who underwent clampless LPN were unselected and consecutive, and the
      procedure was performed at the end of surgeon's learning curve. Patients were
      divided into two groups according to warm ischaemia time (WIT): group A,
      conventional LPN and group B, clampless-LPN (WIT = 0 min). Demographic and peri
      operative data were collected and analysed and functional outcomes were evaluated
      using biochemical markers and renal scintigraphy at baseline and at 3 months
      after surgery. The percentage loss of renal function, evaluated according to
      renal scintigraphy, was calculated. Chi-squared and Student's t-tests were
      carried out and regression analysis was performed. RESULTS: Group A was found to
      be similar to group B in all variables measured except for WIT and blood loss (P
      < 0.001). The percentage reduction in renal scintigraphy values was not
      significantly different between the groups (reductions of 5% in group A and 6% in
      group B for split renal function [SRF] and 12% in group A and 17% in group B for
      estimated renal plasmatic flow [ERPF]; P = 0.587 and P = 0.083, respectively).
      Multivariate analysis in group B showed that the lower the baseline values of SRF
      and ERPF, the poorer the postoperative functional outcome of the treated kidney.
      CONCLUSIONS: In our experience, even clampless LPN was not found to be
      functionally harmless. The patients who benefitted most from a clampless approach
      were those with the poorest baseline renal function.

PMID- 24913696
TI  - Abstracts of the 18th International Symposium on Bioluminescence and
      Chemiluminescence, June 23-28 2014, Uppsala, Sweden-(ISBC 2014).

PMID- 24913700
TI  - Response to Editorial Comment to Modified penile disassembly technique for boys
      with epispadias and those undergoing complete primary repair of exstrophy: long
      term outcomes.

PMID- 24913701
TI  - Scanning electron microscope evidence of telocytes in vasculature.
AB  - Here, we here present scanning electron microscope data for the existent
      telocytes (TCs) on the endothelial surface of the wall of pig coronary arteries,
      internal thoracic arteries and carotid arteries. These cells have a small (8.39
      +/- 1.97 MUm/4.95 +/- 0.91 MUm) cell body of different shapes (from round to
      triangular, depending on the number of cellular prolongations) with very long (of
      about 30 MUm) and thin cellular processes called telopodes (Tps), which have
      uneven calibre. The number of Tps ranges between 2 and 6. Tps typically present
      the alternation of podoms and podomers, and also have a dichotomic branching
      pattern. These data could influence the current attempts for elucidating the
      role(s) of TCs.

PMID- 24913702
TI  - Development of the posterior basic rhythm in children with autism.
AB  - OBJECTIVE: Early detection of autism is critical for effective intervention, but
      currently, no simple screening tests are available. Furthermore, little is known
      about the development of brain dynamics in young children. We examine the early
      neurophysiological manifestations of autism by retrospectively analyzing EEG. In
      particular, we focus on maturation of the posterior basic rhythm (PBR), which is
      one of the most characteristic features of the normal EEG, and comprises a
      discrete functional state. METHODS: Subjects with a diagnosis of autism (n=74),
      as well as normal (n=134) and epileptic (n=108) controls, were extracted
      retrospectively from our digital EEG database. Segments with clear PBR were
      extracted, and standard signal analysis methods were used to calculate peak PBR
      frequency, power, and coherence. RESULTS: In our cohort, a subset of autistic
      children show accelerated development of the PBR, with early maturation
      especially in the 2- to 4-year old range. The overall coherence of PBR-specific
      activity is also lower in autistic children in our cohort. CONCLUSIONS: These
      findings provide evidence that autism is associated with accelerated development
      of the PBR. SIGNIFICANCE: These findings generate a clinical hypothesis for
      future prospective studies on the efficacy of these simple measures as a
      diagnostic or screening tool.

PMID- 24913703
TI  - Integrating the interactome and the transcriptome of Drosophila.
AB  - BACKGROUND: Networks of interacting genes and gene products mediate most cellular
      and developmental processes. High throughput screening methods combined with
      literature curation are identifying many of the protein-protein interactions
      (PPI) and protein-DNA interactions (PDI) that constitute these networks. Most of
      the detection methods, however, fail to identify the in vivo spatial or temporal
      context of the interactions. Thus, the interaction data are a composite of the
      individual networks that may operate in specific tissues or developmental stages.
      Genome-wide expression data may be useful for filtering interaction data to
      identify the subnetworks that operate in specific spatial or temporal contexts.
      Here we take advantage of the extensive interaction and expression data available
      for Drosophila to analyze how interaction networks may be unique to specific
      tissues and developmental stages. RESULTS: We ranked genes on a scale from
      ubiquitously expressed to tissue or stage specific and examined their interaction
      patterns. Interestingly, ubiquitously expressed genes have many more interactions
      among themselves than do non-ubiquitously expressed genes both in PPI and PDI
      networks. While the PDI network is enriched for interactions between tissue
      specific transcription factors and their tissue-specific targets, a preponderance
      of the PDI interactions are between ubiquitous and non-ubiquitously expressed
      genes and proteins. In contrast to PDI, PPI networks are depleted for
      interactions among tissue- or stage- specific proteins, which instead interact
      primarily with widely expressed proteins. In light of these findings, we present
      an approach to filter interaction data based on gene expression levels normalized
      across tissues or developmental stages. We show that this filter (the percent
      maximum or pmax filter) can be used to identify subnetworks that function within
      individual tissues or developmental stages. CONCLUSIONS: These observations
      suggest that protein networks are frequently organized into hubs of widely
      expressed proteins to which are attached various tissue- or stage-specific
      proteins. This is consistent with earlier analyses of human PPI data and suggests
      a similar organization of interaction networks across species. This organization
      implies that tissue or stage specific networks can be best identified from
      interactome data by using filters designed to include both ubiquitously expressed
      and specifically expressed genes and proteins.

PMID- 24913704
TI  - Acupuncture with manual and electrical stimulation for labour pain: a
      longitudinal randomised controlled trial.
AB  - BACKGROUND: Acupuncture is commonly used to reduce pain during labour despite
      contradictory results. The aim of this study is to evaluate the effectiveness of
      acupuncture with manual stimulation and acupuncture with combined manual and
      electrical stimulation (electro-acupuncture) compared with standard care in
      reducing labour pain. Our hypothesis was that both acupuncture stimulation
      techniques were more effective than standard care, and that electro-acupuncture
      was most effective. METHODS: A longitudinal randomised controlled trial. The
      recruitment of participants took place at the admission to the labour ward
      between November 2008 and October 2011 at two Swedish hospitals . 303 nulliparous
      women with normal pregnancies were randomised to: 40 minutes of manual
      acupuncture (MA), electro-acupuncture (EA), or standard care without acupuncture
      (SC). PRIMARY OUTCOME: labour pain, assessed by Visual Analogue Scale (VAS).
      SECONDARY OUTCOMES: relaxation, use of obstetric pain relief during labour and
      post-partum assessments of labour pain. The sample size calculation was based on
      the primary outcome and a difference of 15 mm on VAS was regarded as clinically
      relevant, this gave 101 in each group, including a total of 303 women. RESULTS:
      Mean estimated pain scores on VAS (SC: 69.0, MA: 66.4 and EA: 68.5), adjusted
      for: treatment, age, education, and time from baseline, with no interactions did
      not differ between the groups (SC vs MA: mean difference 2.6, 95% confidence
      interval [CI] -1.7-6.9 and SC vs EA: mean difference 0.6 [95% CI] -3.6-4.8).
      Fewer number of women in the EA group used epidural analgesia (46%) than women in
      the MA group (61%) and SC group (70%) (EA vs SC: odds ratio [OR] 0.35; [95% CI]
      0.19-0.67). CONCLUSIONS: Acupuncture does not reduce women's experience of labour
      pain, neither with manual stimulation nor with combined manual and electrical
      stimulation. However, fewer women in the EA group used epidural analgesia thus
      indicating that the effect of acupuncture with electrical stimulation may be
      underestimated. These findings were obtained in a context with free access to
      other forms of pain relief. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01197950.

PMID- 24913705
TI  - TPM3, a strong prognosis predictor, is involved in malignant progression through
      MMP family members and EMT-like activators in gliomas.
AB  - Recent studies have shown that many molecular mechanisms, such as the EGFR, AKT,
      STAT3, and beta-catenin pathways, are involved in glioma. However, the prognosis
      of the disease remains poor. Explorations of the underlying mechanisms of glioma
      and identification of effective markers for early diagnosis and accurate
      prognostication remain important today. In this study, we employed survival
      analysis to determine that TPM3 overexpression was significantly associated with
      high-grade gliomas and higher mortality. Using microarray combined with Pearson
      correlation analysis, we found that TPM3 was positively correlated with the
      expression of MMP family members and EMT-like activators. Reduction of TPM3 (via
      TPM3-siRNA) inhibited cellular invasion and migration and decreased MMP-9 and
      SNAI1 levels in glioma cells. To the best of our knowledge, our work is the first
      to show that TPM3 plays a critical role in the progression of gliomas and
      provides novel insights into the key roles of MMP family members and EMT-like
      activators that mediate TPM3 functional signaling for glioma regulation.

PMID- 24913706
TI  - Epigenetic alteration of p16 and retinoic acid receptor beta genes in the
      development of epithelial ovarian carcinoma.
AB  - Silencing of tumor suppressor and tumor-related genes by promoter
      hypermethylation is one of the major events in ovarian carcinogenesis. In this
      study, we analyzed aberrant promoter methylation of p16 and RAR-beta genes in 134
      epithelial ovarian carcinomas (EOCs), 23 low malignant potential (LMP) tumors, 26
      benign cystadenomas, and 15 normal ovarian tissues. Methylation was investigated
      by methylation-specific PCR (MSP), and the results were confirmed by bisulfite
      DNA sequencing. Relative gene expression of p16 and RAR-beta was done using
      quantitative reverse transcriptase PCR (qRT-PCR) on 51 EOC cases, 9 LMP tumors,
      and 7 benign cystadenomas with 5 normal ovarian tissues. Aberrant methylation for
      p16 and RAR-beta was present in 43 % (58/134) and 31 % (41/134) in carcinoma
      cases, 22 % (05/23) and 52 % (12/23) in LMP tumors, and 42 % (11/26) and 69 %
      (18/26) in benign cystadenomas. No methylation was observed in any of the normal
      ovarian tissues. The mRNA expression level of p16 and RAR-beta was significantly
      downregulated in EOC and LMP tumors than the corresponding normal tissues whereas
      the expression level was normal in benign cystadenomas for p16 and slightly
      reduced for RAR-beta. A significant correlation of p16 promoter methylation was
      observed with reduced gene expression in EOC. For RAR-beta, no significant
      correlation was observed between promoter methylation and gene expression. Our
      results suggest that epigenetic alterations of p16 and RAR-beta have an important
      role in ovarian carcinogenesis and that mechanism along with methylation plays a
      significant role in downregulation of RAR-beta gene in ovarian cancer.

PMID- 24913707
TI  - Prognostic value of CD44 and CD44v6 expression in patients with non-small cell
      lung cancer: meta-analysis.
AB  - We sought to clarify the prognostic value of CD44 in survival of patients with
      non-small cell lung cancer (NSCLC). We performed a meta-analysis of relevant
      literature to aggregate the available survival results, using studies published
      in English until March 2014. Eligible studies dealt with CD44, CD44 standard form
      (CD44s) and CD44 variant 6 (CD44v6), assessment in NSCLC patients on primary
      lesions and reported survival data according to CD44 and CD44 isoforms
      expression. We aggregated 10 trials (5 trials for CD44v6, 3 trials for CD44, and
      2 trials for CD44s) comprising 1,074 patients, in this meta-analysis. The
      combined hazard ratio (HR) with CD44v6 and CD44s was 2.39 (95 % confidence
      interval (CI) 1.69-3.37) and 1.64 (95 % CI 1.06-2.52), respectively. It
      associated high CD44v6 and CD44s expression with poor survival in NSCLC patients.
      However, CD44 overexpression did not significantly correlate with survival in
      patients with NSCLC (HR 1.44; 95 % CI 0.72-2.89). Our meta-analysis shows that
      CD44v6 and CD44s overexpression indicates poor prognosis for NSCLC patients.
      However, the high CD44 expression is not significantly correlated with survival
      for patients with NSCLC.

PMID- 24913708
TI  - Establishment of experimental implantation tumor models of hepatocellular
      carcinoma in Wistar rats.
AB  - Our aims were to investigate and establish simple and reliable implanted
      hepatocellular carcinoma (HCC) models in Wistar rats. Concentrated suspensions of
      CBRH-7919 cancer cell lines were injected subcutaneously into the scapular
      regions of nude mice. The developing tumor tissues were then implanted into the
      livers of 45 adult Wistar rats. Dexamethasone (2.5 mg/day) was injected
      intramuscularly daily for 1 week preoperatively and 2 weeks postoperatively.
      After 4 weeks of implantation, ultrasonography and nuclear magnetic resonance
      imaging (MRI) were performed to identify model rats with liver tumor growth and
      to analyze the growth and characteristics of the tumors. Five of these model rats
      were then sacrificed, and the tumors were removed from the liver for pathological
      examination. Three rats died during the operation; among the remaining 42 rats,
      36 possessed a total of 43 liver tumors. The success rate of tumor implantation
      was 85.7 % (36/42), and the diameters of the tumors ranged from 5 to 10 mm. All
      tumor specimens were confirmed to be HCC by pathological examination. This study
      provides a new approach for establishing implanted HCC models in Wistar rats,
      which can be used for studying numerous biological features of HCC.

PMID- 24913709
TI  - Role of IL-17F T7488C polymorphism in carcinogenesis: a meta-analysis.
AB  - Previous case-control studies on the association of interleukin-17F (IL-17F)
      T7488C polymorphism and cancer risk have yielded conflicting and inconclusive
      findings. We performed a meta-analysis by pooling all currently available data to
      acquire a more precise estimation of the association. A comprehensive literature
      screening from the PubMed, Embase, Web of Science, and Wanfang databases was
      performed for eligible publications without language restrictions. The pooled
      odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CIs) were
      calculated. According to the inclusion criteria, a total of nine case-control
      studies with 3,034 cases and 3,694 controls were included. Overall, the pooled
      ORs showed that IL-17F T7488C polymorphism was associated with neither increased
      nor decreased risk of cancer. However, the IL-17F T7488C polymorphism exerted
      risk effect on cancer in population-based case-control studies when stratifying
      analysis by source of controls (C vs T OR = 1.24, 95 % CI, 1.10-1.40, pooled OR
      (POR) < 0.001; TC vs TT OR = 1.28, 95 % CI, 1.11-1.48, POR = 0.001; CC + TC vs TT
      OR = 1.29, 95 % CI, 1.12-1.48, POR < 0.001). Additionally, the variant genotypes
      of IL-17F T7488C could alter the risk of gastric cancer under the following
      comparisons (C vs T OR = 1.29, 95 % CI, 1.13-1.47, POR < 0.001; TC vs TT OR =
      1.35, 95 % CI, 1.14-1.60, POR < 0.001; CC + TC vs TT OR = 1.35, 95 % CI, 1.15
      1.58, POR < 0.001). Sensitivity analysis by sequential omission of single study
      did not materially alter the pooled findings. The present meta-analysis suggests
      that the IL-17F T7488C polymorphism may modify the risk of cancer, particularly
      gastric cancer. However, the precise association needs to be elucidated by more
      individual studies with sufficient statistical power.

PMID- 24913710
TI  - Relationships between VEGF protein expression and pathological characteristics of
      diffuse large B cell lymphoma: a meta-analysis.
AB  - We carried out the current meta-analysis of relevant cohort studies in an attempt
      to investigate the relationships between vascular endothelial growth factor
      (VEGF) expression and pathological characteristics of diffuse large B cell
      lymphoma (DLBCL). The following electronic databases were searched for relevant
      articles without any language restrictions: Web of Science (1945 ~ 2013), the
      Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~
      2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~
      2013). Meta-analyses were conducted with the use of STATA software (version 12.0,
      Stata Corporation, College Station, TX, USA). Odds ratios (ORs) and its 95 %
      confidence interval (95 % CI) were calculated. Nine clinical cohort studies with
      a total of 789 DLBCL patients met our inclusion criteria. The meta-analysis
      results showed that patients with positive VEGF expression had higher
      international prognostic index (IPI) scores than VEGF-negative patients (OR =
      5.12, 95 % CI = 2.70 ~ 9.71, P < 0.001). There was a significantly positive
      association between positive VEGF expression and evaluated lactate dehydrogenase
      (LDH) levels (OR = 2.50, 95 % CI = 1.36 ~ 4.60, P = 0.003). We also found that
      patients with positive B symptoms had increased level of VEGF expression (OR =
      2.02, 95 % CI = 1.08 ~ 3.77, P = 0.027). The findings of our meta-analysis
      provide reliable evidence that VEGF expression may be strongly correlated with
      pathological characteristics of DLBCL.

PMID- 24913711
TI  - The mutational burden of acral melanoma revealed by whole-genome sequencing and
      comparative analysis.
AB  - Acral melanoma is a subtype of melanoma with distinct epidemiological, clinical
      and mutational profiles. To define the genomic alterations in acral melanoma, we
      conducted whole-genome sequencing and SNP array analysis of five metastatic
      tumours and their matched normal genomes. We identified the somatic mutations,
      copy number alterations and structural variants in these tumours and combined our
      data with published studies to identify recurrently mutated genes likely to be
      the drivers of acral melanomagenesis. We compared and contrasted the genomic
      landscapes of acral, mucosal, uveal and common cutaneous melanoma to reveal the
      distinctive mutational characteristics of each subtype. 

PMID- 24913712
TI  - Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone
      amide derivatives.
AB  - A series of novel naphthoquinone amide derivatives of the bioactive quinones,
      plumbagin, juglone, menadione and lawsone, with various amino acids were
      synthesized. The compounds were characterized by (1)H NMR, (13)C NMR, Mass, IR
      and elemental analysis. All the compounds were evaluated for their anticancer
      activity against HeLa and SAS cancer cell lines and 3D-QSAR indicated the
      presence of electron donating group near sulphur enhanced the activity against
      HeLa cells. Among the derivatives synthesized, compounds 11f, 10a, 10b and 10g
      were the most active with IC50 values of 16, 12, 14 and 24.5 MUM, respectively.
      The analogues were also screened for antimicrobial activity against two human
      bacterial pathogens, the Gram-positive Methicillin resistant Staphylococcus
      aureus (MRSA) and the Gram-negative Pseudomonas aeruginosa and a human yeast
      pathogen, Fluconazole resistant Candida albicans (FRCA). Among the synthesized
      compounds, 8g, 10g and 11g exhibited maximum antibacterial activity towards MRSA
      and antifungal activity against FRCA in well diffusion method.

PMID- 24913714
TI  - Discovery of a novel series of potent MK2 non-ATP competitive inhibitors using
      1,2-substituted azoles as cis-amide isosteres.
AB  - A unified strategy was conceived and implemented to deliver conformationally
      constrained anilides based on their preferred cis-amide conformers. The
      imidazole/triazole mimicing amide bonds were designed, building upon an earlier
      discovery of a novel series of tricyclic lactams MK2 kinase inhibitors. This
      approach enabled rapid, modular synthesis of structurally novel analogs. The
      efficient SAR development led to the discovery of low molecular weight and potent
      MK2 non-ATP competitive inhibitors with good ligand efficiency, which led to
      improved permeability and oral exposure in rats. 

PMID- 24913715
TI  - Rapid assessment of the illegal presence of 1,3-dimethylamylamine (DMAA) in
      sports nutrition and dietary supplements using 1H NMR spectroscopy.
AB  - 1,3-Dimethylamylamine (DMAA) is a stimulant that can be found in pre-workout
      sports nutrition and dietary supplements. This practice is illegal because DMAA
      is not a safe food ingredient but rather an unapproved medicinal compound due to
      its pharmacological action. In order to determine the DMAA content in such
      products, a nuclear magnetic resonance (NMR) spectroscopic method was developed
      and validated (DMAA was quantified as DMAA-HCl). For quantification, the
      collective integral from two of the methyl groups of the molecule in the range
      delta 0.92-0.84 ppm was used. The method was linear over the examined range of 1
      21 g/kg (R(2) = 0.9937). The recoveries from spiked concentrations (0.1-6 g/kg)
      ranged between 85% and 105% (96% on average), with a relative standard deviation
      (RSD) of 1% for an authentic sample. The detection limit was 0.03 g/kg and the
      quantification limit was 0.08 g/kg (calculated for 75 mg sample weight). The
      actual DMAA-HCl content in the sample was quantified using calibration curves
      (external standardization) or 3,5-dinitrobenzoic acid as single-point internal
      standard. The developed NMR methodology was applied for the analysis of 16
      products, from which 9 samples were found positive (the DMAA-HCl concentration
      varied between 3.1 g/kg and 415 g/kg). The method can be recommended for routine
      use in food testing, customs or doping control laboratories.

PMID- 24913713
TI  - Selective immunoproteasome inhibitors with non-peptide scaffolds identified from
      structure-based virtual screening.
AB  - As a major component of the crucial nonlysosomal protein degradation pathway in
      the cells, the proteasome has been implicated in many diseases such as
      Alzheimer's disease, Huntington's disease, inflammatory bowel diseases,
      autoimmune diseases, multiple myeloma (MM) and other cancers. There are two main
      proteasome subtypes: the constitutive proteasome which is expressed in all
      eukaryotic cells and the immunoproteasome which is expressed in immune cells and
      can be induced in other cell types. Majority of currently available proteasome
      inhibitors are peptide backbone-based, having short half-lives in the body. It is
      highly desirable to identify novel, immunoproteasome-selective inhibitors with
      non-peptide scaffolds for development of novel therapeutics. Through combined
      virtual screening and experimental studies targeting the immunoproteasome, we
      have identified a set of novel immunoproteasome inhibitors with diverse non
      peptide scaffolds. Some of the identified inhibitors have significant selectivity
      for the immunoproteasome over the constitutive proteasome. Unlike most of the
      currently available proteasome inhibitors, these new inhibitors lacking
      electrophilic pharmacophores are not expected to form a covalent bond with
      proteasome after the binding. These non-peptide scaffolds may provide a new
      platform for future rational drug design and discovery targeting the
      immunoproteasome. 

PMID- 24913716
TI  - Potential upstream regulators of cannabinoid receptor 1 signaling in prostate
      cancer: a Bayesian network analysis of data from a tissue microarray.
AB  - BACKGROUND: The endocannabinoid system regulates cancer cell proliferation, and
      in prostate cancer a high cannabinoid CB1 receptor expression is associated with
      a poor prognosis. Down-stream mediators of CB1 receptor signaling in prostate
      cancer are known, but information on potential upstream regulators is lacking.
      RESULTS: Data from a well-characterized tumor tissue microarray were used for a
      Bayesian network analysis using the max-min hill-climbing method. In non
      malignant tissue samples, a directionality of pEGFR (the phosphorylated form of
      the epidermal growth factor receptor) -> CB1 receptors were found regardless as
      to whether the endocannabinoid metabolizing enzyme fatty acid amide hydrolase
      (FAAH) was included as a parameter. A similar result was found in the tumor
      tissue, but only when FAAH was included in the analysis. A second regulatory
      pathway, from the growth factor receptor ErbB2 -> FAAH was also identified in the
      tumor samples. Transfection of AT1 prostate cancer cells with CB1 receptors
      induced a sensitivity to the growth-inhibiting effects of the CB receptor agonist
      CP55,940. The sensitivity was not dependent upon the level of receptor
      expression. Thus a high CB1 receptor expression alone does not drive the cells
      towards a survival phenotype in the presence of a CB receptor agonist.
      CONCLUSIONS: The data identify two potential regulators of the endocannabinoid
      system in prostate cancer and allow the construction of a model of a dysregulated
      endocannabinoid signaling network in this tumor. Further studies should be
      designed to test the veracity of the predictions of the network analysis in
      prostate cancer and other solid tumors.

PMID- 24913718
TI  - Mechanisms that can promote peripheral B-cell lymphoma in ATM-deficient mice.
AB  - The Ataxia Telangiectasia-mutated (ATM) kinase senses DNA double-strand breaks
      (DSB) and facilitates their repair. In humans, ATM deficiency predisposes to B-
      and T-cell lymphomas, but in mice it leads only to thymic lymphomas. We tested
      the hypothesis that increased DSB frequency at a cellular oncogene could promote
      B-cell lymphoma by generating ATM-deficient mice with a V(D)J recombination
      target (DJbeta cassette) within c-myc intron 1 ("DA" mice). We also generated ATM
      deficient mice carrying an EMU-Bcl-2 transgene (AB mice) to test whether enhanced
      cellular survival could promote B-cell lymphomas. About 30% of DA or AB mice and
      nearly 100% of mice harboring the combined genotypes (DAB mice) developed mature
      B-cell lymphomas. In all genotypes, B-cell tumors harbored oncogenic c-myc
      amplification generated by breakage-fusion-bridge (BFB) from dicentric
      chromosomes formed through fusion of IgH V(D)J recombination-associated DSBs on
      chromosome 12 to sequences downstream of c-myc on chromosome 15. AB tumors
      demonstrate that B lineage cells harboring spontaneous DSBs leading to IgH/c-myc
      dicentrics are blocked from progressing to B-cell lymphomas by cellular apoptotic
      responses. DA and DAB tumor translocations were strictly linked to the cassette,
      but occurred downstream, frequently in a 6-kb region adjacent to c-myc that
      harbors multiple cryptic V(D)J recombination targets, suggesting that bona fide
      V(D)J target sequences may activate linked cryptic targets. Our findings indicate
      that ATM deficiency allows IgH V(D)J recombination DSBs in developing B cells to
      generate dicentric translocations that, via BFB cycles, lead to c-myc-activating
      oncogenic translocations and amplifications in mature B cells.

PMID- 24913717
TI  - STING ligand c-di-GMP improves cancer vaccination against metastatic breast
      cancer.
AB  - Cancer vaccination may be our best and most benign option for preventing or
      treating metastatic cancer. However, breakthroughs are hampered by immune
      suppression in the tumor microenvironment. In this study, we analyzed whether
      cyclic diguanylate (c-di-GMP), a ligand for stimulator of interferon genes
      (STING), could overcome immune suppression and improve vaccination against
      metastatic breast cancer. Mice with metastatic breast cancer (4T1 model) were
      therapeutically immunized with an attenuated Listeria monocytogenes (LM)-based
      vaccine, expressing tumor-associated antigen Mage-b (LM-Mb), followed by multiple
      low doses of c-di-GMP (0.2 MUmol/L). This treatment resulted in a striking and
      near elimination of all metastases. Experiments revealed that c-di-GMP targets
      myeloid-derived suppressor cells (MDSC) and tumor cells. Low doses of c-di-GMP
      significantly increased the production of IL12 by MDSCs, in correlation with
      improved T-cell responses to Mage-b, whereas a high dose of c-di-GMP (range, 0.3
      3 mmol/L) activated caspase-3 in the 4T1 tumor cells and killed the tumor cells
      directly. On the basis of these results, we tested one administration of high
      dose c-di-GMP (3 mmol/L) followed by repeated administrations of low-dose c-di
      GMP (0.2 MUmol/L) in the 4T1 model, and found equal efficacy compared with the
      combination of LM-Mb and c-di-GMP. This finding correlated with a mechanism of
      improved CD8 T-cell responses to tumor-associated antigens (TAA) Mage-b and
      Survivin, most likely through cross-presentation of these TAAs from c-di-GMP
      killed 4T1 tumor cells, and through c-di-GMP-activated TAA-specific T cells. Our
      results demonstrate that activation of STING-dependent pathways by c-di-GMP is
      highly attractive for cancer immunotherapy.

PMID- 24913719
TI  - Effects of obesity/fatty acids on the expression of GPR120.
AB  - SCOPE: The effects that fatty acids (FAs) exert on G protein-coupled receptor-120
      (GPR120) levels, a receptor for FAs, are still unknown. We analyzed the
      association between GPR120 and obesity, and the FA effects on its expression.
      METHODS AND RESULTS: GPR120 levels were analyzed in visceral adipose tissue (VAT)
      from nonobese and morbidly obese subject. VAT GPR120 mRNA and protein levels were
      lower in morbidly obese subjects (p = 0.004). After, these subjects underwent a
      high-fat meal. GPR120 mRNA expression in peripheral blood mononuclear cells in
      the fasting state was lower in morbidly obese subjects (p = 0.04), with a
      decrease 3 h after a high-fat meal only in morbidly obese subjects (p = 0.043).
      Also, incubations of visceral adipocytes from these subjects were made with
      different FAs. In nonobese subjects, palmitic, oleic, linoleic, and
      docosahexaenoic acids produced an increase in GPR120 mRNA and protein levels (p <
      0.05). In morbidly obese subjects, only linoleic acid produced an increase in
      GPR120 mRNA and protein levels (p < 0.05). CONCLUSION: Morbidly obese subjects
      had lower GPR120 mRNA and protein levels in VAT and a lower mRNA expression after
      a high-fat meal in peripheral blood mononuclear cells. The FAs effect on GPR120
      mRNA and protein levels in visceral adipocytes was lower in morbidly obese
      subjects.

PMID- 24913720
TI  - Dietary interventions (plant sterols, stanols, omega-3 fatty acids, soy protein
      and dietary fibers) for familial hypercholesterolaemia.
AB  - BACKGROUND: A cholesterol-lowering diet and several other dietary interventions
      have been suggested as a management approach either independently or as an
      adjuvant to drug therapy in children and adults with familial
      hypercholesterolaemia (FH). However, a consensus has yet to be reached on the
      most appropriate dietary treatment. Plant sterols are commonly used in FH
      although patients may know them by other names like phytosterols or stanols.
      OBJECTIVES: To examine whether a cholesterol-lowering diet is more effective in
      reducing ischaemic heart disease and lowering cholesterol than no dietary
      intervention in children and adults with familial hypercholesterolaemia. Further,
      to compare the efficacy of supplementing a cholesterol-lowering diet with either
      omega-3 fatty acids, soya proteins, plant sterols or plant stanols. SEARCH
      METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Inborn Errors of Metabolism Trials Register, which is compiled from electronic
      searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated
      with each new issue of The Cochrane Library), quarterly searches of MEDLINE and
      the prospective handsearching of one journal - Journal of Inherited Metabolic
      Disease. Most recent search of the Group's Inborn Errors of Metabolism Trials
      Register: 22 August 2013. We also searched PubMed to 05 February 2012. SELECTION
      CRITERIA: Randomised controlled trials, both published and unpublished, where a
      cholesterol-lowering diet in children and adults with familial
      hypercholesterolaemia has been compared to other forms of dietary treatment or to
      no dietary intervention were included. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed the trial eligibility and risk of bias and one extracted
      the data, with independent verification of data extraction by a colleague. MAIN
      RESULTS: In the 2014 update of the review, 15 trials have been included, with a
      total of 453 participants across seven comparison groups. The included trials had
      either a low or unclear risk of bias for most of the parameters used for risk
      assessment. Only short-term outcomes could be assessed due to the short duration
      of follow up in the included trials. None of the primary outcomes, (incidence of
      ischaemic heart disease, number of deaths and age at death) were evaluated in any
      of the included trials. No significant differences were noted for the majority of
      secondary outcomes for any of the planned comparisons. However, a significant
      difference was found for the following comparisons and outcomes: for the
      comparison between plant sterols and cholesterol-lowering diet (in favour of
      plant sterols), total cholesterol levels, mean difference 0.30 mmol/l (95%
      confidence interval 0.12 to 0.48); decreased serum LDL cholesterol, mean
      difference -0.60 mmol/l (95% CI -0.89 to -0.31). Fasting serum HDL cholesterol
      levels were elevated, mean difference -0.04 mmol/l (95% CI -0.11 to 0.03) and
      serum triglyceride concentration was reduced, mean difference -0.03 mmol/l (95%
      CI -0.15 to -0.09), although these changes were not statistically significant.
      Similarly, guar gum when given as an add on therapy to bezafibrate reduced total
      cholesterol and LDL levels as compared to bezafibrate alone. AUTHORS'
      CONCLUSIONS: No conclusions can be made about the effectiveness of a cholesterol
      lowering diet, or any of the other dietary interventions suggested for familial
      hypercholesterolaemia, for the primary outcomes: evidence and incidence of
      ischaemic heart disease, number of deaths and age at death,due to the lack of
      data on these. Large, parallel, randomised controlled trials are needed to
      investigate the effectiveness of a cholesterol-lowering diet and the addition of
      omega-3 fatty acids, plant sterols or stanols, soya protein, dietary fibers to a
      cholesterol-lowering diet.

PMID- 24913721
TI  - The role of alpha blockers prior to removal of urethral catheter for acute
      urinary retention in men.
AB  - BACKGROUND: Acute urinary retention is a urological emergency in men and requires
      urgent catheterisation. Any intervention which aims at improving urinary symptoms
      following an acute urinary retention episode could be potentially beneficial.
      Alpha blockers relax prostatic smooth muscle cells thereby decreasing the
      resistance to urinary flow and by doing so could improve urinary symptoms.
      OBJECTIVES: To assess the effectiveness of alpha blockers on successful
      resumption of micturition following removal of a urethral urinary catheter after
      an episode of acute urinary retention in men. In the absence of internationally
      agreed outcome measures for the success of a trial without catheter, success was
      defined as the return to satisfactory voiding without need for re-catheterisation
      within 24 hours. SEARCH METHODS: We searched the Cochrane Incontinence Group
      Specialised Trials Register, which contains trials identified from the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, and
      handsearching of journals and conference proceedings (searched 9 October 2013),
      CENTRAL (2013, Issue 5) (searched 5 June 2013), MEDLINE 1946 to May Week 4 2013,
      MEDLINE in Process (covering to 3 June 2013), EMBASE Classic and EMBASE 1947 to
      2013 Week 22 (all searched 4 June 2013) and the reference lists of relevant
      articles. No language or other restrictions were imposed on the searches.
      SELECTION CRITERIA: Only randomised and quasi-randomised clinical trials of alpha
      blockers for trial without a urethral catheter following an episode of acute
      urinary retention in men were included. DATA COLLECTION AND ANALYSIS: Two review
      authors independently examined all the citations and abstracts derived from the
      search strategy. Any disagreement about trial selection and inclusion was
      resolved by discussion. A third independent judgement was sought where
      disagreement persisted. Two review authors extracted independently, cross-checked
      and processed the data as described in the Cochrane Handbook for Systematic
      Reviews of Intervention. Quality of evidence of the critical outcomes was
      assessed by adopting the GRADE approach. MAIN RESULTS: Nine randomised clinical
      trials were included in this review. Eight trials compared alpha blockers versus
      placebo (five trials tested alfuzosin and two trials tested tamsulosin, one trial
      tested both alfuzosin and tamsulosin, one trial tested silodosin) and one trial
      compared an alpha blocker (doxazosin) versus no treatment. Trial without catheter
      was performed after treatment with the drug for one to three days in seven trials
      and for eight and 32 days in two other trials respectively. There was moderate
      quality evidence to suggest that the rate of successful trial without catheter
      favoured alpha blockers over placebo ( 366/608, 60.2%, of men using an alpha
      blocker were able to void spontaneously after catheter removal compared with
      185/486, 38.1%, using placebo, risk ratio (RR) 1.55, 95% confidence interval (CI)
      1.36 to 1.76). The incidence of recurrent acute urinary retention was lower in
      groups treated with an alpha blocker (RR 0.69, 95% CI 0.60 to 0.79). This
      evidence was of moderate quality and was statistically significant for alfuzosin,
      tamsulosin and silodosin, though not for doxazosin. Of the trials mentioning
      adverse effects (for example, postural hypotension, dizziness), there was not
      enough information to detect statistically significant differences between the
      groups (RR 1.19, 95% CI 0.75 to 1.89) and the evidence was of low quality.
      Overall, adverse effect rates were low for both placebo and alpha blockers and,
      for example, vasodilatation-related adverse effects did not often result in
      discontinuation. AUTHORS' CONCLUSIONS: There was some evidence to suggest that
      alpha blockers increase the success rates of trial without catheter, and the
      incidence of adverse effects was low. There was some evidence of a decreased
      incidence of acute urinary retention. The need for further surgery, cost
      effectiveness and recommended duration of alpha blocker treatment after
      successful trial without catheter remain unknown as these were not reported by
      any trial. There is a lack of internationally agreed outcome measures for what
      constitutes successful trial without catheter. This makes meta-analysis
      difficult. Large, well-designed controlled trials, which use the recommendations
      set out in the CONSORT statement, and include clinically important outcome
      measures, are required.

PMID- 24913722
TI  - Singing as an adjunct therapy for children and adults with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is a genetically inherited, life-threatening
      condition that affects major organs. The management of cystic fibrosis involves a
      multi-faceted daily treatment regimen that includes airway clearance techniques,
      pancreatic enzymes and other medications. Previous studies have found that
      compliance with this intensive treatment is poor, especially among adolescents.
      Because of both the nature and consequences of the illness and the relentless
      demands of the treatment, many individuals with cystic fibrosis have a poor
      quality of life. Anecdotal reports suggest that singing may provide both
      appropriate exercise for the whole respiratory system and a means of emotional
      expression which may enhance quality of life. OBJECTIVES: To evaluate the effects
      of singing as an adjunct therapy to standard treatment on the quality of life,
      morbidity, respiratory muscle strength and pulmonary function of children and
      adults with cystic fibrosis. SEARCH METHODS: We searched the Group's Cystic
      Fibrosis Trials Register and the Cochrane Central Register of Controlled Trials.
      Date of latest search: 31 March 2014.We also searched major allied complementary
      data bases, and clinical trial registers. Additionally, we handsearched relevant
      conference proceedings and journals. Date of latest search: 24 May 2012.
      SELECTION CRITERIA: Randomised controlled trials in which singing (as an adjunct
      intervention) is compared with either a control intervention (for example,
      playing computer games or doing craft activities) or no singing in people with
      cystic fibrosis. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed
      against pre-determined criteria for inclusion. Only one eligible trial was
      available for analysis. MAIN RESULTS: Since only one small study was included, no
      meta-analysis could be performed. The included study was a parallel, randomised
      controlled trial undertaken at two paediatric hospitals in Australia. The study
      evaluated the effects of a singing program on the quality of life and respiratory
      muscle strength of hospitalised children with cystic fibrosis (mean age 11.6
      years, 35% male). While the singing group received eight individual singing
      sessions, the control group participated in preferred recreational activities,
      such as playing computer games or watching movies. This study was limited by a
      small sample size (51 participants) and a high drop-out rate (21%). There were no
      significant differences between the groups at either post-intervention or follow
      up; although by the end of treatment there were some within-group statistically
      significant increases for both singing and control groups in some of the domains
      of the quality of life questionnaire Cystic Fibrosis Questionnaire-Revised (e.g.
      emotional, social and vitality domains). For the respiratory muscle strength
      indices, maximal expiratory pressure at follow up (six to eight weeks post
      intervention) was higher in the singing group, mean difference 25.80 (95%
      confidence interval 5.94 to 45.66). There was no significant difference between
      groups for any of the other respiratory function parameters (maximal inspiratory
      pressure, spirometry) at either post-intervention or follow up. AUTHORS'
      CONCLUSIONS: There is insufficient evidence to determine the effects of singing
      on quality of life or on the respiratory parameters in people with cystic
      fibrosis. However, there is growing interest in non-medical treatments for cystic
      fibrosis and researchers may wish to investigate the impact of this inexpensive
      therapy on respiratory function and psychosocial well-being further in the
      future.

PMID- 24913723
TI  - Plasma and cerebrospinal fluid amyloid beta for the diagnosis of Alzheimer's
      disease dementia and other dementias in people with mild cognitive impairment
      (MCI).
AB  - BACKGROUND: According to the latest revised National Institute of Neurological
      and Communicative Disorders and Stroke and the Alzheimer's Disease and Related
      Disorders Association (now known as the Alzheimer's Association) (NINCDS-ADRDA)
      diagnostic criteria for Alzheimer's disease dementia of the National Institute on
      Aging and Alzheimer Association, the confidence in diagnosing mild cognitive
      impairment (MCI) due to Alzheimer's disease dementia is raised with the
      application of biomarkers based on measures in the cerebrospinal fluid (CSF) or
      imaging. These tests, added to core clinical criteria, might increase the
      sensitivity or specificity of a testing strategy. However, the accuracy of
      biomarkers in the diagnosis of Alzheimer's disease dementia and other dementias
      has not yet been systematically evaluated. A formal systematic evaluation of
      sensitivity, specificity, and other properties of plasma and CSF amyloid beta
      (Abeta) biomarkers was performed. OBJECTIVES: To determine the accuracy of plasma
      and CSF Abeta levels for detecting those patients with MCI who would convert to
      Alzheimer's disease dementia or other forms of dementia over time. SEARCH
      METHODS: The most recent search for this review was performed on 3 December 2012.
      We searched MEDLINE (OvidSP), EMBASE (OvidSP), BIOSIS Previews (ISI Web of
      Knowledge), Web of Science and Conference Proceedings (ISI Web of Knowledge),
      PsycINFO (OvidSP), and LILACS (BIREME). We also requested a search of the
      Cochrane Register of Diagnostic Test Accuracy Studies (managed by the Cochrane
      Renal Group).No language or date restrictions were applied to the electronic
      searches and methodological filters were not used so as to maximise sensitivity.
      SELECTION CRITERIA: We selected those studies that had prospectively well defined
      cohorts with any accepted definition of cognitive decline, but no dementia, with
      baseline CSF or plasma Abeta levels, or both, documented at or around the time
      the above diagnoses were made. We also included studies which looked at data from
      those cohorts retrospectively, and which contained sufficient data to construct
      two by two tables expressing plasma and CSF Abeta biomarker results by disease
      status. Moreover, studies were only selected if they applied a reference standard
      for Alzheimer's dementia diagnosis, for example the NINCDS-ADRDA or Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
      DATA COLLECTION AND ANALYSIS: We screened all titles generated by the electronic
      database searches. Two review authors independently assessed the abstracts of all
      potentially relevant studies. We assessed the identified full papers for
      eligibility and extracted data to create standard two by two tables. Two
      independent assessors performed quality assessment using the QUADAS-2 tool. Where
      data allowed, we derived estimates of sensitivity at fixed values of specificity
      from the model we fitted to produce the summary receiver operating characteristic
      (ROC) curve. MAIN RESULTS: Alzheimer's disease dementia was evaluated in 14
      studies using CSF Abeta42. Of the 1349 participants included in the meta
      analysis, 436 developed Alzheimer's dementia. Individual study estimates of
      sensitivity were between 36% and 100% while the specificities were between 29%
      and 91%. Because of the variation in assay thresholds, we did not estimate
      summary sensitivity and specificity. However, we derived estimates of sensitivity
      at fixed values of specificity from the model we fitted to produce the summary
      ROC curve. At the median specificity of 64%, the sensitivity was 81% (95% CI 72
      to 87). This equated to a positive likelihood ratio (LR+) of 2.22 (95% CI 2.00 to
      2.47) and a negative likelihood ratio (LR-) of 0.31 (95% CI 0.21 to 0.48).The
      accuracy of CSF Abeta42 for all forms of dementia was evaluated in four studies.
      Of the 464 participants examined, 188 developed a form of dementia (Alzheimer's
      disease and other forms of dementia).The thresholds used were between 209 mg/ml
      and 512 ng/ml. The sensitivities were between 56% and 75% while the specificities
      were between 47% and 76%. At the median specificity of 75%, the sensitivity was
      estimated to be 63% (95% CI 22 to 91) from the meta-analytic model. This equated
      to a LR+ of 2.51 (95% CI 1.30 to 4.86) and a LR- of 0.50 (95% CI 0.16 to
      1.51).The accuracy of CSF Abeta42 for non-Alzheimer's disease dementia was
      evaluated in three studies. Of the 385 participants examined, 61 developed non
      Alzheimer's disease dementia. Since there were very few studies and considerable
      variation between studies, the results were not meta-analysed. The sensitivities
      were between 8% and 63% while the specificities were between 35% and 67%.Only one
      study examined the accuracy of plasma Abeta42 and the plasma Abeta42/Abeta40
      ratio for Alzheimer's disease dementia. The sensitivity of 86% (95% CI 81 to 90)
      was the same for both tests while the specificities were 50% (95% CI 44 to 55)
      and 70% (95% CI 64 to 75) for plasma Abeta42 and the plasma Abeta42/Abeta40 ratio
      respectively. Of the 565 participants examined, 245 developed Alzheimer's
      dementia and 87 non-Alzheimer's disease dementia.There was substantial
      heterogeneity between studies. The accuracy of Abeta42 for the diagnosis of
      Alzheimer's disease dementia did not differ significantly (P = 0.8) between
      studies that pre-specified the threshold for determining test positivity (n = 6)
      and those that only determined the threshold at follow-up (n = 8). One study
      excluded a sample of MCI non-Alzheimer's disease dementia converters from their
      analysis. In sensitivity analyses, the exclusion of this study had no impact on
      our findings. The exclusion of eight studies (950 patients) that were considered
      at high (n = 3) or unclear (n = 5) risk of bias for the patient selection domain
      also made no difference to our findings. AUTHORS' CONCLUSIONS: The proposed
      diagnostic criteria for prodromal dementia and MCI due to Alzheimer's disease,
      although still being debated, would be fulfilled where there is both core
      clinical and cognitive criteria and a single biomarker abnormality. From our
      review, the measure of abnormally low CSF Abeta levels has very little diagnostic
      benefit with likelihood ratios suggesting only marginal clinical utility. The
      quality of reports was also poor, and thresholds and length of follow-up were
      inconsistent. We conclude that when applied to a population of patients with MCI,
      CSF Abeta levels cannot be recommended as an accurate test for Alzheimer's
      disease.

PMID- 24913724
TI  - Home- versus hospital-based phototherapy for the treatment of non-haemolytic
      jaundice in infants at more than 37 weeks' gestation.
AB  - BACKGROUND: Phototherapy is commonly used for the treatment of neonatal jaundice,
      and home-based phototherapy is now being used in certain centres. Home-based
      phototherapy offers possible advantages by avoiding prolonged hospital
      admissions, promoting mother-infant bonding and reducing hospitalisation costs.
      Potential problems include increased duration of phototherapy, increased
      readmission to hospital and increased risk of bilirubin encephalopathy.
      OBJECTIVES: To compare exclusively home-based versus exclusively hospital-based
      phototherapy or a combination of home- and hospital-based phototherapy for the
      management of non-haemolytic jaundice in term infants up to 28 days of age. We
      planned to include specific subgroups for duration in hospital, method of
      phototherapy and criteria for readiness for discharge. SEARCH METHODS: We
      searched the Cochrane Neonatal Review Group Specialised Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL) January 2013, Issue 1, part of
      The Cochrane Library, MEDLINE (from 1966 to 15 February 2013), CINAHL (from 1982
      to 15 February 2013) and EMBASE (from 1988 to 15 February 2013). We searched for
      abstracts from the Pediatric Academic Societies' Annual Meetings 2000 to 2013. We
      searched for ongoing trials on the following websites: ClinicalTrials.gov
      (http://clinicaltrials.gov/) and Current Controlled Trials (http://controlled
      trials.com/). SELECTION CRITERIA: Randomised and quasi-randomised studies
      comparing term infants who received phototherapy exclusively at home versus
      phototherapy exclusively in the hospital or a combination of the two for non
      haemolytic jaundice. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. MAIN RESULTS: No studies
      that met the predefined eligibility criteria were identified. AUTHORS'
      CONCLUSIONS: No high-quality evidence is currently available to support or refute
      the practice of home-based phototherapy for non-haemolytic jaundice in infants at
      more than 37 weeks' gestation.

PMID- 24913725
TI  - Combination inhaled corticosteroids and long-acting beta2-agonists for children
      and adults with bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is a major contributor to chronic respiratory
      morbidity and mortality worldwide. Wheeze and other asthma-like symptoms and
      bronchial hyperreactivity may occur in people with bronchiectasis. Physicians
      often use asthma treatments in patients with bronchiectasis. OBJECTIVES: To
      assess the effects of inhaled long-acting beta2-agonists (LABA) combined with
      inhaled corticosteroids (ICS) in children and adults with bronchiectasis during
      (1) acute exacerbations and (2) stable state. SEARCH METHODS: The Cochrane
      Airways Group searched the the Cochrane Airways Group Specialised Register of
      Trials, which includes records identified from the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases. The Cochrane
      Airways Group performed the latest searches in October 2013. SELECTION CRITERIA:
      All randomised controlled trials (RCTs) of combined ICS and LABA compared with a
      control (placebo, no treatment, ICS as monotherapy) in children and adults with
      bronchiectasis not related to cystic fibrosis (CF). DATA COLLECTION AND ANALYSIS:
      Two review authors extracted data independently using standard methodological
      procedures as expected by The Cochrane Collaboration. MAIN RESULTS: We found no
      RCTs comparing ICS and LABA combination with either placebo or usual care. We
      included one RCT that compared combined ICS and LABA with high-dose ICS in 40
      adults with non-CF bronchiectasis without co-existent asthma. All participants
      received three months of high-dose budesonide dipropionate treatment (1600
      micrograms). After three months, participants were randomly assigned to receive
      either high-dose budesonide dipropionate (1600 micrograms per day) or a
      combination of budesonide with formoterol (640 micrograms of budesonide and 18
      micrograms of formoterol) for three months. The study was not blinded. We
      assessed it to be an RCT with overall high risk of bias. Data analysed in this
      review showed that those who received combined ICS-LABA (in stable state) had a
      significantly better transition dyspnoea index (mean difference (MD) 1.29, 95%
      confidence interval (CI) 0.40 to 2.18) and cough-free days (MD 12.30, 95% CI 2.38
      to 22.2) compared with those receiving ICS after three months of treatment. No
      significant difference was noted between groups in quality of life (MD -4.57, 95%
      CI -12.38 to 3.24), number of hospitalisations (odds ratio (OR) 0.26, 95% CI 0.02
      to 2.79) or lung function (forced expiratory volume in one second (FEV1) and
      forced vital capacity (FVC)). Investigators reported 37 adverse events in the ICS
      group versus 12 events in the ICS-LABA group but did not mention the number of
      individuals experiencing adverse events. Hence differences between groups were
      not included in the analyses. We assessed the overall evidence to be low quality.
      AUTHORS' CONCLUSIONS: In adults with bronchiectasis without co-existent asthma,
      during stable state, a small single trial with a high risk of bias suggests that
      combined ICS-LABA may improve dyspnoea and increase cough-free days in comparison
      with high-dose ICS. No data are provided for or against, the use of combined ICS
      LABA in adults with bronchiectasis during an acute exacerbation, or in children
      with bronchiectasis in a stable or acute state. The absence of high quality
      evidence means that decisions to use or discontinue combined ICS-LABA in people
      with bronchiectasis may need to take account of the presence or absence of co
      existing airway hyper-responsiveness and consideration of adverse events
      associated with combined ICS-LABA.

PMID- 24913727
TI  - Association of CYP1B1 L432V polymorphism with urinary cancer susceptibility: a
      meta-analysis.
AB  - BACKGROUND: The Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme involved in the
      metabolism of exogenous and endogenous substrates. Previous studies have reported
      the existence of CYP1B1 L432V missense polymorphism in prostate, bladder and
      renal cancers. However, the effects of this polymorphism on the risk of these
      cancers remain conflicting. Therefore, we performed a meta-analysis to assess the
      association between L432V polymorphism and the susceptibility of urinary cancers.
      METHODS: We searched the PubMed database without limits on language for studies
      exploring the relationship of CYP1B1 L432V polymorphism and urinary cancers.
      Article search was supplemented by screening the references of retrieved studies
      manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated
      to evaluate the strength of these associations. Simultaneously, publication bias
      was estimated by funnel plot and Begg's test with Stata 11 software. RESULTS: We
      observed a significant association between CYP1B1 L432V polymorphism and urinary
      cancers. The overall OR (95% CI) of CC versus CG was 0.937 (0.881-0.996), the
      overall OR (95% CI) of CC versus CG+GG was 0.942 (0.890-0.997). Furthermore, we
      identified reduced risk for CC versus other phenotypes in both prostate and
      overall urinary cancers, when studies were limited to Caucasian or Asian
      patients. CONCLUSIONS: This meta-analysis suggests that the CYP1B1 L432V
      polymorphism is associated with urinary cancer risk. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3108829721231527.

PMID- 24913728
TI  - Prediction of non-relapse mortality in recipients of reduced intensity
      conditioning allogeneic stem cell transplantation with AML in first complete
      remission.
AB  - Non-relapse mortality (NRM) after allogeneic hematopoietic stem cell
      transplantation (alloHSCT) can be predicted by the hematopoietic cell
      transplantation comorbidity index (HCT-CI) and the European Group for Blood and
      Marrow Transplantation (EBMT) score, which are composed of different parameters.
      We set out to integrate the parameters of both scores in patients with acute
      myeloid leukemia (AML) in first complete remission (CR1) receiving reduced
      intensity conditioning (RIC) alloHSCT. All parameters from the HCT-CI and the
      EBMT-score with the addition of patient and donor cytomegalovirus serology were
      evaluated in 812 patients by multivariable analysis with end-point NRM at 2
      years. Subsequently, 16 parameters were selected based on hazard ratio >1.2, and
      were incorporated into a novel score, which was further internally validated by
      bootstrapping. Both the HCT-CI and the EBMT-score showed relatively weak
      predictive value, whereas the integrated score allowed to identify three clearly
      distinct risk groups with 2-year NRM estimates of 8+/-2% (low-risk), 17+/-2%
      (intermediate-risk) and 38+/-4% (high-risk), which also translated in prediction
      of overall survival. Collectively, integration of the most dominant parameters
      from the HCT-CI and the EBMT-score allowed to develop a simple and robust,
      integrated score with improved prediction of NRM for AML patients proceeding to
      RIC alloHSCT in CR1. 

PMID- 24913729
TI  - The mechanistic role of DNA methylation in myeloid leukemogenesis.
AB  - The importance of epigenetic aberrations in the pathogenesis of leukemias has
      been revealed by recurrent gene mutations that highlight epigenetic pathways as
      well as by the clinical success of therapies like 5-azacytidine and decitabine
      that work through epigenetic mechanisms. However, precise mechanisms of how gene
      mutations lead to leukemias and how epigenetic therapies induce clinical
      remissions are elusive. Current scientific inquiries that take advantage of
      techniques that can distinguish among the various covalent cytosine modifications
      at single base resolution are likely to shed light on the ways epigenetic
      pathways drive leukemogenesis as well as how the hypomethylating drugs induce
      clinical remissions. The hope is that these studies will also reveal which
      patients are likely to respond to epigenetic therapies. Thus, the future is
      likely to bring a new wave of diagnostic and prognostic tools that probe the
      epigenomics of leukemia to help clinicians in their management of patients. 

PMID- 24913730
TI  - Usefulness of sentinel node navigation surgery in the management of early tongue
      cancer.
AB  - OBJECTIVE: To determine the validity of sentinel node navigation surgery (SNNS)
      in early stage tongue cancer, the occurrence rate of postoperative cervical
      metastasis (POCM) after lead plate technique (LPT) introduction and survival
      rates in patients who underwent SNNS were analyzed. METHODS: SNNS was performed
      in 29 patients (stage I: 14, stage II: 15) from 2000 to 2007. Tc-labeled phytate
      was prepared as a radiotracer a day before SNNS. The sentinel node (SN) was then
      examined pathologically during surgery. For cases where metastasis in SN was
      positive, neck dissection was performed. Occurrence of POCM after LPT
      introduction was compared with that before LPT introduction. 'Wait and see'
      policy was performed in 52 patients (stage I: 27, stage II: 25) from 1987 to 1999
      as a historical control. The observation period of SNNS cases and 'wait and see'
      policy cases ranged from 10 months to 165 months (median: 91 months) and from 7
      months to 268 months (median: 87 months), respectively. RESULTS: Six of the 29
      SNNS cases (21%) were proven metastatic SNs. Before LPT introduction, POCM
      occurred in 2 of the 15 cases, while we had no occurrences after LPT
      introduction. The 5-year overall survival rate of the 29 patients who underwent
      SNNS and the 52 patients with 'wait and see' policy were 96% and 84%,
      respectively, and there was statistical significance in the two groups (p<0.05).
      CONCLUSIONS: As the survival rate of the patients with the SNNS tended to be
      better than that with the 'wait and see' policy in our cases, SNNS could avoid
      unnecessary neck dissection. SNNS provides useful information regarding decision
      making for neck dissection in early stage tongue cancer.

PMID- 24913731
TI  - Thyroid ala perichondrial flaps for subglottic reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: Techniques available for reconstruction of the
      cricotracheal region in adults are currently suboptimal. We sought to 1)
      understand the anatomic basis for the thyroid ala perichondrial flap, 2) describe
      the technique of harvesting and intraluminal placement, and 3) learn the
      limitations of defects for which it can be used. STUDY DESIGN: Cadaveric
      anatomical study. METHODS: In fresh cadaveric specimens, the perichondrium of the
      outer layer of the thyroid cartilage was elevated by tracing the superior,
      medial, and lateral borders of each thyroid cartilage ala. The inferiorly based
      flap was then placed into the airway through the cricothyroid membrane. The
      extent of coverage was measured. RESULTS: A total of 10 flaps were performed (6
      male and 4 female). The average length of thyroid perichondrial flaps obtained
      was 1.67 cm. All flaps were able to completely cover the cricoid cartilage and
      extended to but did not cover the first tracheal ring. Once placed
      intraluminally, the flaps extended 2.4 cm below the vocal cords. Using both flaps
      enabled coverage of the entire anterior 180 degrees of the airway lumen in all
      specimens. There were no significant differences in male/female or right
      sided/left-sided flaps. CONCLUSIONS: The thyroid ala perichondrial flap is
      technically feasible and can provide coverage of anterior airway defects up to
      approximately 2.4 cm below the true vocal cords. This flap could enable transfer
      of vascularized tissue to aid in cricotracheal reconstruction.

PMID- 24913732
TI  - Asparagine synthetase expression and its potential prognostic value in patients
      with NK/T cell lymphoma.
AB  - Natural killer (NK)/T cell lymphoma usually shows a highly aggressive clinical
      course and the overall prognosis is poor. At present, there are no standard
      therapeutic regimens for this disease. Although chemotherapeutic protocols
      containing L-asparaginase (L-Asp) or pegaspargase (PEG-Asp) have improved the
      efficacy of treatment, some patients are resistant to L-Asp or PEG-Asp. Previous
      studies demonstrated that the elevated expression of asparagine synthetase (ASNS)
      is correlated with the resistance to L-Asp or PEG-Asp and may also affect the
      prognosis in some types of tumors, but the expression level and clinical
      significance of ASNS in NK/T cell lymphoma remain unknown. Therefore, we
      investigated the expression and clinical significance of ASNS in lymphoma cell
      lines and patients with NK/T cell lymphoma. Firstly, we detected PEG-Asp and L
      Asp activity using MTT assay and expression of ASNS using real-time PCR in the 7
      lymphoma cell lines. Secondly, we used branched DNA-liquidchip technology (bDNA
      LCT) for detecting ASNS mRNA in formalin-fixed, paraffin-embedded tissue sections
      in 50 cases of NK/T cell lymphoma and in 12 cases of nasal polyps and chronic
      rhinitis. Moreover, we analyzed the correlations between the expression of ASNS
      and the sensitivity to L-Asp and PEG-Asp in 7 lymphoma cell lines and with
      clinicopathological features and prognosis of NK/T cell lymphoma patients who
      used chemotherapy containing L-Asp and PEG-Asp. There was a marked difference in
      the sensitivity to L-Asp and PEG-Asp of the 7 lymphoma cell lines. YTS and SNK-6
      cells were highly sensitive to PEG-Asp and had relatively low levels of ASNS mRNA
      expression. Hut-78, Jurkat and Karpas 299 cells were naturally resistant to PEG
      Asp, and the ASNS expression levels were extremely high. The expression level of
      ASNS was relatively low in the NK/T cell lymphoma tissue compared to levels in
      the nasal polyps and chronic rhinitis (0.480+/-0.307 vs. 0.739+/-0.267; P=0.009).
      ASNS expression level was associated with III-IV tumor stage (P=0.041) and a high
      International Prognostic Index (P=0.018) in patients with NK/T cell lymphoma. The
      NK/T cell lymphoma patients with higher ASNS expression had a reduced median
      survival time when compared with the survival of patients with low ASNS
      expression (P=0.033). Cox regression test showed that the ASNS expression level
      is an independent prognostic factor for NK/T cell lymphoma patients. In
      conclusion, the expression of ASNS was closely related with the sensitivity of
      lymphoma cell lines to L-Asp and PEG-Asp in vitro and also had a certain effect
      on the survival of NK/T cell lymphoma patients. In conclusion, high ASNS
      expression in NK/T cell lymphoma is correlated with worse clinicopathological
      features.

PMID- 24913733
TI  - Transient facial nerve palsy after occipital nerve block: a case report.
AB  - Occipital nerve blocks are commonly performed to treat a variety of headache
      syndromes and are generally believed to be safe and well tolerated. We report the
      case of an otherwise healthy 24-year-old woman with left side-locked occipital,
      parietal, and temporal pain who was diagnosed with probable occipital neuralgia.
      She developed complete left facial nerve palsy within minutes of blockade of the
      left greater and lesser occipital nerves with a solution of bupivicaine and
      triamcinolone. Magnetic resonance imaging of the brain with gadolinium contrast
      showed no abnormalities, and symptoms had completely resolved 4-5 hours later.
      Unintended spread of the anesthetic solution along tissue planes seems the most
      likely explanation for this adverse event. An aberrant course of the facial nerve
      or connections between the facial and occipital nerves also might have played a
      role, along with the patient's prone position and the use of a relatively large
      injection volume of a potent anesthetic. Clinicians should be aware that
      temporary facial nerve palsy is a possible complication of occipital nerve block.

PMID- 24913734
TI  - Seeing it my way: living with childhood onset visual disability.
AB  - BACKGROUND: Although the significant impact of visual disability in childhood has
      been widely recognized, children's own perspectives of living with a visual
      impairment have not been considered. We report the experiences of visually
      impaired (VI) children and young people aged 10-15 years about growing up with
      impaired sight. METHODS: The participants were 32 VI children and young people,
      aged 10-15 years [visual acuity logarithm of minimum angle of resolution (LogMAR)
      worse than 0.51] recruited through National Health Service (NHS) paediatric
      ophthalmology and developmental vision clinics and 11 VI pupils aged 12-17
      attending a specialist school for pupils with disabilities. Individual semi
      structured interviews with participants captured their experiences of living with
      a visual impairment. A child-centred interview topic guide was developed from a
      literature review, observations at ophthalmology clinics, consultation with
      health and education professionals working with VI children and young people, and
      interviews and a focus group with VI pupils from the specialist school.
      Collaborative qualitative thematic analysis by three researchers identified
      emergent themes. NVivo software was used for coding the data. RESULTS: Analysis
      identified six themes concerning living with a visual impairment: (i) social
      relationships, participation and acceptance; (ii) independence and autonomy;
      (iii) psychological and emotional well-being; (iv) aspirations and concerns about
      the future; (v) functioning - home, school and leisure; and (vi) treatment of eye
      condition. Key issues included: the importance of family and peer support;
      balancing independence, support and safety; the emotional burden and adjustment
      of living with a disability; concerns about education and job prospects in the
      future; functional restrictions and limitations; and ongoing management of the
      eye condition. CONCLUSIONS: The findings offer insights into the complex
      realities of living with visual impairment. They provide the basis for
      development of patient-reported outcome measures. They can also serve to help
      enrich the understanding of health professionals working with VI children and
      young people, potentially enabling them to better support them.

PMID- 24913735
TI  - Biological risk versus socio-economic advantage: low birth-weight, multiple
      births and income variations among Irish infants born following fertility
      treatments.
AB  - The Growing Up in Ireland Infant Cohort dataset (n = 11,134) includes information
      on fertility treatments for over 400 infants. IVF (28.1 %) and IVF-related
      treatments (17.8 %) were the most frequent, but there was also a high percentage
      following clomiphene citrate alone (31.5 %). Infants born following fertility
      treatment were much more likely to be in higher income families, and this
      relationship was not accounted for by older mothers in wealthier families.
      Analysis of fertility-treatment pregnancies among Irish infants, controlling for
      income and maternal age, shows a greater risk of multiple birth and low birth
      weight, although the latter appears to be largely related to the former
      especially for IVF-type treatments.

PMID- 24913736
TI  - The challenges of managing refractory oesphageal lichen planus.
AB  - INTRODUCTION: Lichen planus is an inflammatory mucocutaneous disorder, often
      idiopathic. It is postulated that the characteristic skin lesions arise from a T
      cell mediated autoimmune response against basal keratinocytes. Oral mucosal
      involvement can occur in up to 70 % of cases of cutaneous disease however,
      oesphageal involvement is rare. RESULT: We report the case of a 60 year old
      female with ulcerative oesphagitis and concomitant cutaneous lesions suggestive
      of lichen planus. Multiple immunosuppressant therapies were administered but with
      little success, except for pulses of oral steroids. CONCLUSION: Oesphageal lichen
      planus is rare, often unrecognised and can be resistant to treatment. However,
      diagnosis is crucial as malignant transformation of longstanding ulcerative
      lichen planus may occur.

PMID- 24913737
TI  - Soft tissue reactions in patients with bone anchored hearing aids.
AB  - AIMS: To establish the incidence and correlation between the degree of soft
      tissue reaction and the body mass index (BMI) according to age and gender after a
      bone anchored hearing aid (BAHA) implant. METHODS: We did a 1-9-year follow-up
      for the all the patients who underwent surgery in our department with BAHA
      implant system. Soft tissue reactions were classified in accordance with the
      Holgers classification on regular patient visits. BMI was calculated for each
      patient, and changes were recorded at least once a year. RESULTS: 47 patients
      were evaluated. 58% were operated on for chronic otitis with mixed or conductive
      hearing loss; 20% had unilateral or bilateral atresia and 16% had single sided
      deafness (SSD); other indications were otosclerosis and syndromic patients. The
      grade of Holgers classification significantly correlated at a 0.001 level with
      BMI (Spearmans rho 0.452). Holgers grade also differed significantly between the
      sexes-skin reactions in females were less frequent. An ANOVA test did not reveal
      any statistical difference between patients with dissimilar indications for BAHA.
      CONCLUSION: If performed carefully, BAHA surgery produces a favorable outcome.
      The Holgers grade may change as time passes. If skin reactions appear, they can
      be treated through local or systemic therapy, and they may turn into a normal
      grade. Adipose patients should be treated with special care because they are more
      prone to soft tissue reactions.

PMID- 24913739
TI  - Comparison of double-plate appliance/facemask combination and facemask therapy in
      treating class III malocclusions.
AB  - OBJECTIVE: To compare the treatment effects of double-plate appliance/facemask
      (DPA-FM) combined therapy and facemask (FM) therapy in treating Class III
      malocclusions. MATERIALS AND METHODS: The material consisted of lateral
      cephalometric radiographs of 45 children with skeletal and dental Class III
      malocclusion. The first treatment group comprised 15 patients (mean age  =  11
      years) treated with FM. The second treatment group comprised 15 patients (mean
      age  = 10 years 9 months) treated with DPA-FM. The third group comprised 15
      patients (mean age  =  10 years 5 months) used as controls. The paired t-test was
      used to evaluate the treatment effects and changes during the treatment and
      observation period in each group. Differences between the groups were determined
      by variance analysis and the Duncan test. RESULTS: With the DPA-FM and FM
      appliances, the SNA and ANB angles increased significantly. These changes were
      statistically different compared with the control group. Lower facial height
      showed a greater increase in both treatment groups than in the control group.
      Molar relation showed a greater increase in the DPA-FM group than in the FM
      group. The increase in U6/ANS-PNS angle in the FM group was significantly
      different from the DPA-FM and control groups. The L1/NB angle and Pg-T increased
      significantly only in the FM group, but no significant difference was found
      between the treatment groups. CONCLUSIONS: In the treatment of Class III
      malocclusion, both appliances were effective. The significant sagittal changes in
      the lower incisors and pogonion in the FM group compared with the nonsignificant
      changes in the DPA-FM group might be due to the restriction effect of acrylic
      blocks in the DPA-FM group.

PMID- 24913738
TI  - Coexistence of Fabry disease and IgA nephropathy: a report of two cases.
AB  - BACKGROUND: Coexistence of Fabry disease and IgA nephropathy is rare. Moreover,
      the coexisting Fabry disease may be unrecognized due to unapparent clinical
      manifestations. METHOD: We described two cases with coexisting Fabry disease and
      IgA nephropathy. The clinicopathological features of these two patients were
      studied. RESULTS: A 54-year-old male presented with proteinuria, hematuria, and
      hypertension, and a 33-year-old male presented with proteinuria without clinical
      signs or family history of Fabry disease. Both of them were diagnosed with IgA
      nephropathy at admission, whereas Fabry disease was not suspected. Subsequent
      immunofluorescent study confirmed the diagnosis of IgA nephropathy by showing
      positive staining for IgA and complement C3 in the mesangium. Meanwhile, light
      microscopy showed remarkable vacuolation of podocytes with mild mesangial
      expansion, which was characteristic of Fabry nephropathy. Further examination of
      toluidine blue-stained semi-thin sections and electron microscopy demonstrated
      blue bodies and myelin figures in the cytoplasm of podocytes, respectively. The
      diagnosis of coexisting Fabry disease was finally established based on deficient
      alpha-galactosidase A activity in both patients. CONCLUSION: This case study is
      an important reminder of the role of kidney biopsy as an indicator of Fabry
      disease and its rare coexistence with IgA nephropathy.

PMID- 24913740
TI  - Corticotomy-assisted maxillary protraction with skeletal anchorage and Class III
      elastics.
AB  - OBJECTIVE: To analyze the treatment effects of corticotomy-assisted maxillary
      protraction with skeletal anchorage and Class III elastics in patients with Class
      III malocclusions. MATERIALS AND METHODS: The study group consisted of 19
      patients with a mean age of 13.12 +/- 1.28 years. Initially, patients were
      monitored for 5 months before treatment to evaluate growth changes. Changes
      during control, protraction and fixed orthodontic treatment periods were compared
      with the cephalometric radiographs taken initially, before protraction, after
      protraction, and after fixed orthodontic treatment. Treatment outcomes also were
      compared with the growth effects. RESULTS: Sagittal measurements of maxilla
      showed significant improvements (3.59 +/- 1.32 mm) during the protraction period
      (3.85 +/- 1.12 months) whereas no significant changes were seen during the
      control period. Upper and lower incisor inclinations were increased, and the
      upper occlusal plane angle showed significant counterclockwise rotation during
      protraction. Significant soft-tissue changes also reflected the underlying
      skeletal changes. Maxillary advancement was stable during fixed orthodontic
      treatment. CONCLUSION: Compared with control period of the patients, this
      protocol produced significant improvements in skeletal and soft-tissue
      structures.

PMID- 24913741
TI  - Paper microfluidic-based enzyme catalyzed double microreactor.
AB  - We describe a paper microfluidic-based enzyme catalyzed double microreactor assay
      using fluorescent detection. Here, solutions of lactate dehydrogenase (LDH) and
      diaphorase (DI) were directly spotted onto the microfluidic paper-based
      analytical device (MUPAD). Samples containing lactic acid, resazurin, and
      nicotinamide adenine dinucleotide oxidized form (NAD(+) ), potassium chloride
      (KCl), and BSA, in MES buffer were separately spotted onto the MUPAD and MES
      buffer flowed through the device. A cascade reaction occurs upon the sample spot
      overlapping with LDH to form pyruvate and nicotinamide adenine dinucleotide
      reduced form (NADH). Subsequently, NADH is used in the conversion of resazurin to
      fluorescent resorufin by DI. The MUPAD avoids the need of surface
      functionalization or enzyme immobilization steps. These microreactor devices are
      low cost and easy to fabricate and effect reaction based solely on buffer
      capillary action. 

PMID- 24913744
TI  - Elective neck irradiation versus observation in squamous cell carcinoma of the
      maxillary sinus with N0 neck: A meta-analysis and review of the literature.
AB  - BACKGROUND: Elective neck irradiation of a clinical node-negative (N0) neck in
      squamous cell carcinoma (SCC) of the maxillary sinus is a controversial issue.
      METHODS: A systematic review of electronic databases and a meta-analysis were
      conducted to clarify the role of elective neck irradiation in patients with SCC
      of the maxillary sinus and clinical N0 neck. Regional (neck) nodal recurrence was
      chosen as the primary endpoint. RESULTS: Four retrospective studies with a total
      of 129 patients met the inclusion criteria. The results of the meta-analysis
      showed that elective neck irradiation reduced the risk of regional nodal
      recurrence (fixed effects model: odds ratio [OR] = 0.16; 95% confidence interval
      [CI] = 0.04-0.67; p = .01; random-effects model: OR = 0.17; 95% CI = 0.04-0.76; p
      = .02) compared to observation. CONCLUSION: This systemic review and first meta
      analysis confirmed that elective neck irradiation can significantly reduce the
      rate of nodal recurrence in patients with N0 SCC of the maxillary sinus.

PMID- 24913746
TI  - [Introduction].

PMID- 24913743
TI  - Serum C-reactive protein as an adjunct for identifying complicated parapneumonic
      effusions.
AB  - INTRODUCTION: Distinguishing non-purulent complicated parapneumonic pleural
      effusions (CPPE) from uncomplicated parapneumonic pleural effusions (UPPE) is
      challenging. We aimed to determine whether serum C-reactive protein (sCRP), alone
      or in combination with classical pleural fluid parameters, is useful in making
      such discrimination. METHODS: The study was composed of a total of 104
      consecutive patients, of whom 47 had UPPE and 57 had CPPE. Standard biochemical
      pleural fluid data along with sCRP were measured. RESULTS: sCRP at the time of
      thoracentesis or chest tube insertion was significantly higher in CPPE (238 mg/L)
      than UPPE (147 mg/L). At the optimum cutoff value of 200 mg/L, sCRP had a
      sensitivity, specificity, likelihood ratio positive, likelihood ratio negative,
      and area under the receiver-operating characteristic curve for diagnosing CPPE of
      58 %, 81 %, 3.1, 0.52, and 0.67, respectively. The combination of sCRP >200 mg/L
      with pleural fluid glucose <60 mg/dL using an "and" rule achieved a specificity
      of 98 %, whereas both parameters combined in an "or" rule had a sensitivity of 81
      %, which was higher than that of pleural fluid pH (57 %) or glucose (54 %).
      CONCLUSIONS: sCRP, when combined with classical pleural fluid biochemistries,
      improves the diagnostic accuracy in identifying those patients with non-purulent
      parapneumonic effusions who need chest drainage.

PMID- 24913747
TI  - [Social and health impact of Institutes of Legal Medicine in Spain: beyond
      justice].
AB  - The main mission of Spanish Institutes of Legal Medicine (ILMs) is to serve the
      justice system. We review the potential broader role of the work done by ILMs,
      with an emphasis on forensic pathology. The relevance of forensic information to
      increase the quality of mortality statistics is highlighted, taking into account
      the persistence of the low validity of the external causes of death in the
      Mortality Register that was already detected more than a decade ago. The new
      statistical form and reporting system for the deaths under ILMs jurisdiction, as
      introduced by the Spanish Instituto Nacional de Estadistica in 2009, are also
      described. The IMLs role in the investigation of the following mortality causes
      and of their determinants is reviewed in detail: traffic accidents, suicide,
      drugs of abuse, child deaths and sudden deaths. We conclude that an important
      public role of IMLs is emerging beyond their valuable service to the justice
      system, mainly through the gathering of data critical to assess and prevent
      several medical and public health and safety issues of great social impact and
      through their participation in epidemiologic research and surveillance.

PMID- 24913748
TI  - [Medical-legal conduct with individuals in judicial or police custody].
AB  - The problems involved in caring for individuals in custody, as well as deaths
      that occur during custody, are relevant aspects of legal and forensic medicine in
      terms of the possible criminal, civil and administrative responsibility of health
      professionals and/or public or private institutions that might hold individuals
      in custody and deprived of freedom. The rule of law should ensure that these
      cases comply with state law and international agreements and treaties related to
      human rights and the special treatment of individuals deprived of freedom in
      hospitals or detention centers. Of particular mention is the medical-forensic
      activity regarding deaths associated with the use of control holds and/or
      restraint during the detention of individuals by members of the armed forces or
      law enforcement or in healthcare centers by safety and healthcare personnel. In
      these cases, both the immediate healthcare treatment subsequent to the events and
      the medical-forensic study should be particularly careful. These situations,
      which are often high profile, cause social alarm and involve judicial actions
      that can result in especially severe liabilities. 

PMID- 24913749
TI  - [Forensic assessment of violence risk].
AB  - Over the last 20 years there have been steps forward in the field of scientific
      research on prediction and handling different violent behaviors. In this work we
      go over the classic concept of "criminal dangerousness" and the more current of
      "violence risk assessment". We analyze the evolution of such assessment from the
      practice of non-structured clinical expert opinion to current actuarial methods
      and structured clinical expert opinion. Next we approach the problem of assessing
      physical violence risk analyzing the HCR-20 (Assessing Risk for Violence) and we
      also review the classic and complex subject of the relation between mental
      disease and violence. One of the most problematic types of violence, difficult to
      assess and predict, is sexual violence. We study the different actuarial and
      sexual violence risk prediction instruments and in the end we advise an integral
      approach to the problem. We also go through partner violence risk assessment,
      describing the most frequently used scales, especially SARA (Spouse Assault Risk
      Assessment) and EPV-R. Finally we give practical advice on risk assessment,
      emphasizing the importance of having maximum information about the case, carrying
      out a clinical examination, psychopathologic exploration and the application of
      one of the described risk assessment scales. We'll have to express an opinion
      about the dangerousness/risk of future violence from the subject and some
      recommendations on the conduct to follow and the most advisable treatment.

PMID- 24913751
TI  - [Assessment of psychological conditions for the use of firearms in law
      enforcement].
AB  - To handle firearms safely, an individual needs to be in sound psychological
      conditions. This point is especially relevant in law enforcement, given that this
      group is likely to experience situations where there is a reasonably severe risk
      to life, physical integrity and that of third parties. These conditions cause
      high levels of stress and become a significant source of psychological strain.
      The assessment of these psychological conditions in law enforcement must stay
      ahead of this strain and should act preventively, establishing surveillance that
      is the product of a consensus between the needs of professionals and
      organizations. This evaluation should be conducted by technical specialists who
      understand and know the occupational reality of these professionals. A good
      assessment methodology starts with the need to discover the basic areas that need
      exploring, the ideal procedure for assessing these issues and the criteria that
      determine the aptitude (or lack thereof) for handling firearms. Once these goals
      have been established, we can be assured that the assessment will follow a set of
      principles that will give it homogeneity, effectiveness and efficiency. This type
      of assessment will help accomplish the mission that these security professionals
      are entrusted to by law, which is to protect the free exercise of rights and
      freedoms and ensure citizen safety. 

PMID- 24913750
TI  - [Medical-legal issues of physical and pharmacological restraint].
AB  - The use of physical and pharmacological restraint is controversial but is
      currently accepted as inevitable. It is indicated for controlling behavioral
      disorders and psychomotor agitation that put patients and third parties at risk.
      Its indication should be medical, and we should opt for the least restrictive
      measure. Restraints represent a possible infringement of patients' fundamental
      rights and require understanding and strict respect for the medical-legal
      precepts by physicians and other practitioners involved in its application. This
      article reviews the current legal framework, as well as the medical-legal
      premises and aspects of applying restraints, with the objective of ensuring
      maximum respect for patients' rights and the appropriate legal safety in the
      activity of practitioners. 

PMID- 24913753
TI  - [Toxicological evaluation in the childhood].
AB  - Intoxications in infancy require urgent medical treatment within national health
      systems. In our country they represent 0.3% of paediatric urgencies. Most of them
      are accidental intoxications but is not infrequent to find some related to child
      abuse or to suicidal intentions, especially in adolescence. The objectives of the
      study are to evaluate both clinical health care and medical legal aspects in
      intoxications in infancy. Medical assistance is described and it includes
      clinical diagnosis, typology of the more common toxics, percentages and referral
      to social work and emergency care equipment units of the Ministry of Social
      Welfare and the Department of Health or, where appropriate, directly to
      prosecutors and courts for their intervention. In cases of detection of alcohol,
      drugs or medication in infants, the importance of the correct interpretation of
      the results of toxicological findings is discussed. Several studies for the
      interpretation of results concerning the detection of these toxics are reported.
      Both legal aspects and the forensic medical opinion are assessed. The findings
      will be analysed by the judicial authority in order to circumscribe
      responsibilities or to take appropriate decisions concerning the protection of
      infants' interests. In conclusion intoxication in infancy can lead to legal
      proceedings requiring specific actions for their protection. Both physicians and
      hospitals must comply with the legal requirement of the submission to the court
      of judicial parties. On the other hand, this information is an interesting step
      toward reinforcing public health surveillance.

PMID- 24913752
TI  - [Temporary disability and its legal implications].
AB  - Temporary disability is the condition that workers face when, as the result of
      illness (common or professional) or accident (work-related or not), they are
      temporarily prevented from performing their work and require health care. The
      management of temporary disability is a medical act that involves (in addition to
      a complex clinical assessment) obvious social, occupational and financial
      connotations and requires continuing medical follow-up from doctors, as well as
      responses to medical-legal conflicts. The regulatory framework on the subject is
      extensive in the Spanish setting and highly diverse in the European setting.
      Beyond the regulatory framework, the repercussions of temporary disability are
      self-evident at all levels. Although determining temporary disability is a common
      medical act for practicing physicians, it is not exempt from risks or
      difficulties arising from the assessment itself and the characteristics of
      practicing medical care. Established medical-legal conflicts include the
      processing of health data and the requirements for transferring information
      related to workers' temporary disability to their company's medical services. The
      interest and usefulness demonstrated by the data obtained from forensic medicine
      for public health require the incorporation of these data into general healthcare
      information, as it could be essential to the surveillance of worker health. The
      recommendations established by medical societies, as good practice guidelines,
      are especially useful in this type of conflict. 

PMID- 24913754
TI  - [Surgical procedures involved in claims for alleged defects in praxis].
AB  - Medical professional liability and adverse events in health care are major
      concerns worldwide and the analysis of claims for alleged defects in praxis is a
      potential source of knowledge. High rates of adverse events and complaints have
      been reported in surgical procedures. This article analyzes the claims registered
      by the Council of Medical Colleges in Catalonia between 1986 and 2012, and
      explores surgical procedures claimed (ICD- 9-CM coding), as well as the final
      outcome of the claim. Among the 5,419 records identified on surgical procedures,
      the interventions of the musculoskeletal system and skin and integument showed
      the highest frequencies. Interventions related to "non-curative" medicine should
      be emphasized because of their higher rates of economical agreement or
      condemnation outcomes, which were significantly higher for mastopexia. The
      results underscore the importance of the surgical area in medical professional
      liability and the high risk of payouts among those procedures belonging to the so
      called "non-curative" medicine.

PMID- 24913755
TI  - [Urological diseases most frequently involved in medical professional liability
      claims].
AB  - Clinical safety and medical professional liability are international major
      concerns, especially in surgical specialties such as urology. This article
      analyzes the claims filed at the Council of Medical Colleges of Catalonia between
      1990 and 2012, exploring urology procedures. The review of the 173 cases
      identified in the database highlighted the importance of surgical procedures
      (74%). Higher frequencies related to scrotal-testicular pathology (34%),
      especially testicular torsion (7.5%) and vasectomy (19.6%), and prostate
      pathology (26 %), more specifically the surgical treatment of benign prostatic
      hyperplasia (17.9%). Although urology is not among the specialties with the
      higher frequency of claims, there are special areas of litigation in which it is
      advisable to implement improvements in clinical safety.

PMID- 24913756
TI  - Upconversion nanoparticles as a contrast agent for photoacoustic imaging in live
      mice.
AB  - An inclusion complex of NaYF4 :Yb(3+) ,Er(3+) upconversion nanoparticles with
      alpha-cyclodextrin in aqueous conditions exhibits luminescence quenching when
      excited at 980 nm. This non-radiative relaxation leads to an unprecedented
      photoacoustic signal enhancement. In vivo localization of alpha-cyclodextrin
      covered NaYF4 :Yb(3+) ,Er(3+) is demonstrated using photoacoustic tomography in
      live mice, showing its high capability for photoacoustic imaging. 

PMID- 24913757
TI  - Time and the domain of consciousness.
AB  - It is often thought that there is little that seems more obvious from experience
      than that time objectively passes, and that time is, in this respect, quite
      unlike space. Yet nothing in the physical picture of the world seems to
      correspond to the idea of such an objective passage of time. In this paper, I
      discuss some attempts to explain this apparent conflict between appearance and
      reality. I argue that existing attempts to explain the conflict as the result of
      a perceptual illusion fail, and that it is, in fact, the nature of memory, rather
      than perception, that explains why we are inclined to think of time as passing. I
      also offer a diagnosis as to why philosophers have sometimes been tempted to
      think that an objective passage of time seems to figure directly in perceptual
      experience, even though it does not. 

PMID- 24913758
TI  - Whole slide imaging diagnostic concordance with light microscopy for breast
      needle biopsies.
AB  - This study investigated the diagnostic accuracy of whole slide imaging (WSI) in
      breast needle biopsy diagnosis in comparison with standard light microscopy (LM).
      The study examined the effects of image capture magnification and computer
      monitor quality on diagnostic concordance of WSI and LM. Four pathologists
      rendered diagnoses using WSI to examine 85 breast biopsies (92 parts; 786 slides)
      consisting of benign and malignant cases. Each WSI case was evaluated using
      images captured at either *20 or *40 magnifications and viewed using a Digital
      Imaging and Communication in Medicine (DICOM) grade, color-calibrated monitor or
      a standard, desktop liquid-crystal display (LCD) monitor. For each combination,
      the WSI result was compared with the original, LM diagnosis. The overall
      concordance rate observed between WSI and LM was 97.1% (95% confidence intervals
      [CI]: 94.3%-98.5%). After a washout period, all cases were reviewed a second time
      by each pathologist after using LM, and the second LM diagnosis was compared with
      the WSI diagnosis rendered by the same pathologist. Intraobserver concordance
      between WSI and LM was 95.4% (95% CI: 92.2%-97.4%). The second LM diagnoses were
      also compared with the original LM diagnoses, and the observed interobserver LM
      concordance rate was 97.3% (95% CI: 93.1%-99.0%). The study data demonstrated
      that breast needle biopsy diagnoses rendered by WSI were equivalent to diagnoses
      rendered by LM. No diagnostic differences were detected between the underlying
      viewing system parameters of monitor quality and image capture resolution. The
      results of this study demonstrated that WSI can be effectively used in
      subspecialty diagnostic cases where a minimum amount of tissue is available.

PMID- 24913759
TI  - A review and correction of the errors in Loftus and Guyer on Jane Doe.
AB  - There are so many errors among those facts that can be checked in the Loftus and
      Guyer articles under review that they cast doubt on the accuracy of the alleged
      facts in these articles that cannot be easily checked. Loftus's and Guyer's two
      articles, published in a newsstand magazine instead of a peer-reviewed journal,
      show a pattern of inaccuracy that casts doubt on their claims to have conducted a
      skeptical, objective inquiry. Some, but not all of these errors, were corrected
      in a 2009 article Geis and Loftus published in a peer-reviewed journal, although
      Loftus does not acknowledge in that article her earlier inaccuracies. This
      article corrects the record about the conclusions drawn in the Corwin and Olafson
      article published in 1997 and clarifies the history about Corwin's involvement in
      the Taus case. 

PMID- 24913760
TI  - Protecting scientists, science, and case protagonists: a discussion of the Taus
      v. Loftus commentaries.
AB  - This article is a discussion of the articles by Nicole Taus Kluemper, Erna
      Olafson, Frank Putnam, Laura Brown, Ross Cheit, and Gerald Koocher. The papers
      center on the issues raised by a decision by two psychologists to break the
      confidentiality of a case study published by David Corwin and Erna Olafson to
      gather information to support an alternative theoretical view of the case. The
      article reviews best understandings of the justifications proposed by the
      psychologists, who saw themselves as investigative reporters, discusses the
      papers that have been submitted, and proposes enhanced ethical guidelines and
      increased professional discussion of these issues. 

PMID- 24913761
TI  - Eid-ul-Azha festival in Pakistan: a vulnerable time for Crimean-Congo hemorrhagic
      fever outbreak.

PMID- 24913762
TI  - Influence of whole-body washing of critically ill patients with chlorhexidine on
      Acinetobacter baumannii isolates.
AB  - BACKGROUND: Acinetobacter baumannii is 1 of the most important nosocomial
      pathogens and the causative agent of numerous types of infections, especially in
      intensive care units (ICUs). Our aim was to evaluate the effect of 2%
      chlorhexidine gluconate (CHG) whole-body washing of ICU patients on A baumannii
      in a tertiary care hospital. METHODS: During the 6-month intervention period, 327
      patients were subjected to whole-body bath with 2% CHG-impregnated wipes. blaIMP
      (active on imipenem), blaVIM (Verona integron-encoded metallo-beta-lactamase),
      and blaoxacillinase (OXA) of A baumannii were typed. Isolates were genotyped by
      pulsed-field gel electrophoresis. Minimum inhibitory concentrations (MIC) to CHG
      were determined by the agar dilution method and drug susceptibility determined
      using the broth microdilution method. Biofilm formation was determined by crystal
      violet staining. RESULTS: We analyzed 80 isolates during the baseline period and
      69 isolates during the intervention period. There was a decrease in the MIC50 and
      MIC90 values for CHG for isolates (8 mg/L and 16 mg/L, respectively). All
      isolates typed positive for OXA51-like and 86% typed positive for OXA24-like
      pulsed-field gel electrophoresis identified 2 main clone types. During the
      intervention period the frequency of clone A decreased and that of clone B
      increased. Both clones were OXA24-like positive. CONCLUSIONS: The A baumannii
      isolates recovered from patients who received body washing with 2% CHG presented
      with a significant decrease in CHG MIC values associated with a change in
      clonality correlating with increased biofilm production.

PMID- 24913763
TI  - Evaluation of an education and training intervention to reduce health care waste
      in a tertiary hospital in Spain.
AB  - BACKGROUND: In recent decades there has been a significant increase in waste
      generation. Training interventions in advanced health care waste management can
      improve the segregation of regulated medical waste and reduce volume and costs.
      METHODS: We carried out a quasi-experimental intervention study with before and
      after training session analysis to compare waste segregation. Descriptive
      analysis of the segregated health care waste and an evaluation of the quality of
      segregation were done. A comparison of monthly average waste to assess the
      effectiveness of the educational intervention was performed. RESULTS: After the
      intervention, there was a significant reduction in the monthly average health
      care waste volume of 6.2%. Statistically significant differences in the
      infectious waste and genotoxic/pharmaceutical waste weight segregated before and
      after the intervention (P < .05) were found. Because of the health care waste
      weight reduction and the improvement of waste classification, a savings cost of
      ?125,205 was achieved. CONCLUSIONS: The health care waste management training
      improves biomedical waste segregation at the hospital, reducing the health care
      waste volume and costs as an added value.

PMID- 24913764
TI  - Effect of feeding cassava (Manihot esculenta Crantz) root meal on growth
      performance, hydrocyanide intake and haematological parameters of broiler chicks.
AB  - The effect of feeding cassava root meal on growth performance, hydrocyanide
      intake, haematological indices and serum thiocyanate concentration of broiler
      chicks was investigated using 300-day-old male broilers. There were five dietary
      treatments arranged in a 2 * 2 + 1 factorial arrangement of two processing
      methods of cassava root (peeled and unpeeled) included at two levels (100 and 200
      g/kg) plus a control diet (maize-based diet, containing no cassava root). Each
      treatment was replicated six times with ten birds per replicate. The feeding
      trial lasted for 28 days. Control-fed birds had the highest overall (P < 0.01)
      final liveweight and weight gain, least (P < 0.05) hydrocyanide (HCN) intake and
      best (P < 0.05) feed-to-gain ratio. Chicks fed with control and diet containing
      100 g/kg peeled cassava root meal (PCRM) had the least (P < 0.05) feed cost per
      weight gain. Chicks fed with diet containing 100 g/kg cassava root meal had
      higher (P < 0.05) final liveweight and weight gain and reduced (P < 0.05) HCN
      intake than chicks fed with diet containing 200 g/kg cassava root meal. Dietary
      inclusion of peeled cassava root meal (PCRM) for broiler chicks resulted in
      increased final liveweight (P < 0.05), weight gain (P < 0.01) and feed intake (P
      < 0.01) when compared with birds fed with diet containing unpeeled cassava root
      meal (UCRM). The least (P < 0.01) final liveweight and weight gain and worst (P <
      0.05) feed-to-gain ratio were obtained with chicks fed with diet containing 200
      g/kg UCRM. Increased dietary inclusion levels of cassava root resulted in
      significant increase (P < 0.05) in white blood cell (WBC) count, heterophil count
      and serum thiocyanate concentration. In comparison with chicks fed with diet
      containing UCRM, dietary inclusion of PCRM resulted in increased (P < 0.05) red
      blood cell (RBC) count and haemoglobin (Hb) concentration and reduced (P < 0.05)
      white blood cell (WBC) count and serum thiocyanate concentration. Although
      inclusion of 100 g/kg PCRM showed some economic sense, dietary inclusion of
      either peeled or unpeeled cassava root poses a threat on growth and health status
      of broiler chicks.

PMID- 24913766
TI  - Is thrombophilia associated with placenta-mediated pregnancy complications? A
      prospective cohort study: comment.

PMID- 24913765
TI  - A child with anaphylactic reaction by egg remedy applied to burn.

PMID- 24913767
TI  - Central vasopressin V1A receptor blockade alters patterns of cellular activation
      and prevents glucocorticoid habituation to repeated restraint stress exposure.
AB  - Our previous experiments implicated a role for the arginine vasopressin (AVP) V1A
      receptor subtype in mediating the normal decline (habituation) of hypothalamic
      pituitary-adrenal (HPA) axis responses to repeated restraint exposure. To explore
      pathways mediating the endogenous effects of central AVP on stress HPA axis
      habituation, here we compared cellular (Fos) and hormone responses in male rats
      receiving chronic icv infusion of vehicle or a V1A receptor antagonist that began
      7 d before stress testing, continued through the duration of acute and repeat
      restraint exposure. As a group, rats with V1A antagonism displayed a modest
      reduction in ACTH habituation, whereas the decline in corticosterone was
      completely prevented. V1A antagonized rats also showed reduced evidence of
      habituated Fos responses in the paraventricular nucleus of the hypothalamus,
      medial amygdala, and within the anterior division of the bed nucleus of the stria
      terminalis. Based on these cellular and neuroendocrine responses, we then
      examined whether repeated restraint is reflected by changes in V1A receptor
      binding. Relative to stress naive animals, repeatedly exposed rats showed lower
      levels of V1A binding in the dentate gyrus of the hippocampus, thalamus and
      central amygdala, but higher levels in the septum and anterior BST. Taken
      together, these findings suggest that AVP may act within multiple targets to
      regulate the normal decline in stress-induced drive to the HPA axis, and that
      this may involve the net of V1A receptor stimulatory and inhibitory influences on
      neuroendocrine habituation.

PMID- 24913768
TI  - Self-organizing microfluidic crystals.
AB  - We consider how to design a microfluidic system in which suspended particles
      spontaneously order into flowing crystals when driven by external pressure. Via
      theory and numerics, we find that particle-particle hydrodynamic interactions
      drive self-organization under suitable conditions of particle morphology and
      geometric confinement. Small clusters of asymmetric "tadpole" particles, strongly
      confined in one direction and weakly confined in another, spontaneously order in
      a direction perpendicular to the external flow, forming one dimensional lattices.
      Large suspensions of tadpoles exhibit strong density heterogeneities and form
      aggregates. By rationally tailoring particle shape, we tame this aggregation and
      achieve formation of large two-dimensional crystals. 

PMID- 24913769
TI  - Induction of osteoclast progenitors in inflammatory conditions: key to bone
      destruction in arthritis.
AB  - The inflammatory milieu favors recruitment and activation of osteoclasts, and
      leads to bone destruction as a serious complication associated with arthritis and
      with other inflammatory processes. The frequency and activity of osteoclast
      progenitors (OCPs) correspond to arthritis severity, and may be used to monitor
      disease progression and bone resorption, indicating the need for detailed
      characterization of the discrete OCP subpopulations. Collectively, current
      studies suggest that the most potent murine bone marrow OCP population can be
      identified among lymphoid negative population within the immature myeloid lineage
      cells, as B220(-)CD3(-)CD11b(-/lo)CD115(+)CD117(+)CX3CR1(+) and possibly also
      Ter119(-)CD11c(-)CD135(lo)Ly6C(+)RANK(-). In peripheral blood the OCP population
      bears the monocytoid phenotype B220(-)CD3(-)NK1.1(
      )CD11b(+)Ly6C(hi)CD115(+)CX3CR1(+), presumably expressing RANK in committed OCPs.
      Much less is known about human OCPs and their regulation in arthritis, but the
      circulating OCP subset is, most probably, comprised among the lymphoid negative
      population (CD3(-)CD19(-)CD56(-)), within immature monocyte subset
      (CD11b(+)CD14(+)CD16(-)), expressing receptors for M-CSF and RANKL
      (CD115(+)RANK(+)). Our preliminary data confirmed positive association between
      the proportion of peripheral blood OCPs, defined as CD3(-)CD19(-)CD56(
      )CD11b(+)CD14(+), and the disease activity score (DAS28) in the follow-up samples
      from patients with psoriatic arthritis receiving anti-TNF therapy. In addition,
      we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs
      and enhance their differentiation potential, thus mediating osteoresorption.
      Control of the activity and migratory behaviour of OCPs as well as the
      identification of crucial bone/joint chemotactic mediators represent promising
      therapeutic targets in arthritis.

PMID- 24913770
TI  - Biologic augmentation of rotator cuff repair with mesenchymal stem cells during
      arthroscopy improves healing and prevents further tears: a case-controlled study.
AB  - PURPOSE: The purpose of this study was to evaluate the efficiency of biologic
      augmentation of rotator cuff repair with iliac crest bone marrow-derived
      mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re
      tears were correlated with the number of MSCs received at the tendon-to-bone
      interface. METHODS: Forty-five patients in the study group received concentrated
      bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the
      time of arthroscopy. The average number of MSCs returned to the patient was
      51,000 +/- 25,000. Outcomes of patients receiving MSCs during their repair were
      compared to those of a matched control group of 45 patients who did not receive
      MSCs. All patients underwent imaging studies of the shoulder with iterative
      ultrasound performed every month from the first postoperative month to the 24th
      month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively
      at three and six months, one and two years and at the most recent follow up MRI
      (minimum ten-year follow-up). RESULTS: Bone marrow-derived MSC injection as an
      adjunctive therapy during rotator cuff repair enhanced the healing rate and
      improved the quality of the repaired surface as determined by ultrasound and MRI.
      Forty-five (100 %) of the 45 repairs with MSC augmentation had healed by six
      months, versus 30 (67 %) of the 45 repairs without MSC treatment by six months.
      Bone marrow concentrate (BMC) injection also prevented further ruptures during
      the next ten years. At the most recent follow-up of ten years, intact rotator
      cuffs were found in 39 (87 %) of the 45 patients in the MSC-treated group, but
      just 20 (44 %) of the 45 patients in the control group. The number of
      transplanted MSCs was determined to be the most relevant to the outcome in the
      study group, since patients with a loss of tendon integrity at any time up to the
      ten-year follow-up milestone received fewer MSCs as compared with those who had
      maintained a successful repair during the same interval. CONCLUSION: This study
      showed that significant improvement in healing outcomes could be achieved by the
      use of BMC containing MSC as an adjunct therapy in standard of care rotator cuff
      repair. Furthermore, our study showed a substantial improvement in the level of
      tendon integrity present at the ten-year milestone between the MSC-treated group
      and the control patients. These results support the use of bone marrow-derived
      MSC augmentation in rotator cuff repair, especially due to the enhanced rate of
      healing and the reduced number of re-tears observed over time in the MSC-treated
      patients.

PMID- 24913771
TI  - An adult multifocal medulloblastoma with diffuse acute postoperative cerebellar
      swelling: immunohistochemical and molecular genetics analysis.
AB  - Medulloblastoma (MB), the most common malignant tumor typically affecting
      children, occurs only exceptionally in adults. Multifocal presentation of this
      malignancy in adulthood is even much rarer-only four cases with favorable
      postoperative course have been reported, so far. The study illustrates a very
      rare rapid postoperative clinical deterioration due to diffuse cerebellar
      swelling (DCS) in an adult multifocal MB (MMB). To the best of their knowledge,
      authors for the first time performed genetic analysis of MMB and demonstrated
      expression patterns of selected markers that put the patient within the sonic
      hedgehog (SHH) molecular subgroup and at least partially explain her
      unsatisfactory clinical course. Herein, authors summarized the relevant
      literature concerning this issue with the aim to determine features that would
      facilitate diagnosis and therapy of such a scarce clinical entity.

PMID- 24913772
TI  - Effect of siRNA against NF-kappaB on sepsis-induced acute lung injury in a mouse
      model.
AB  - The aim of the present study was to explore the protective effect of small
      interfering RNA (siRNA) against nuclear factor kappaB (NF-kappaB) p65 on sepsis
      induced acute lung injury (ALI) in mice. In total, 70 male Kunming mice were
      randomly divided into a healthy control group, a sepsis group, a specific
      interfering group and a scrambled control group (Sc), and the latter three groups
      were divided into post-operational 6 and 12 h subgroups, each of which consisted
      of 10 mice. The mice were administered with NF-kappaB siRNA, scrambled siRNA and
      normal saline via tail vein injection. Following 1 h, a mouse model of septic ALI
      was produced by cecal ligation and puncture (CLP) in the two siRNA groups and the
      sepsis control group. At 6 and 12 h post-operation, the experimental mice were
      sacrificed and the lung tissue samples were collected. Histopathological changes,
      wet/dry ratio of lung weight, NF-kappaB protein and NF-kappaB p65 mRNA levels,
      matrix metalloproteinase-9 (MMP-9) mRNA and protein activity were detected.
      Compared with the sepsis group and the Sc at the corresponding time, the
      expression levels of NF-kappaB p65 mRNA, the lung injury of experimental mice,
      the wet/dry ratio and the levels of MMP-9 mRNA and protein activity decreased,
      and significant differences were observed at 6 h post-operation (P<0.05). RNA
      interference against NF-kappaB p65 was able to decrease the expression of NF
      kappaB and further inhibit the early phasic excessive inflammatory reaction in
      sepsis, which may alleviate ALI. 

PMID- 24913773
TI  - Halothane-induced hepatitis: paradigm or paradox for drug-induced liver injury.

PMID- 24913774
TI  - Spine immobilization algorithm revisited.

PMID- 24913775
TI  - Novel action and mechanism of auranofin in inhibition of vascular endothelial
      growth factor receptor-3-dependent lymphangiogenesis.
AB  - Auranofin is a gold compound initially developed for the treatment of rheumatoid
      arthritis. Recent data suggest that auranofin has promise in the treatment of
      other inflammatory and proliferative diseases. However, the mechanisms of action
      of auranofin have not been well defined. In the present study, we identify
      vascular endothelial growth factor receptor-3 (VEGFR3), an endothelial cell (EC)
      surface receptor essential for angiogiogenesis and lymphangiogenesis, as a novel
      target of auranofin. In both primary EC and EC cell lines, auranofin induces
      downregulation of VEGFR3 in a dose-dependent manner. Auranofin at high doses (>=1
      uM) decreases cellular survival protein thioredoxin reductase (TrxR2), TrxR2
      dependent Trx2 and transcription factor NF-kappaB whereas increases stress
      signaling p38MAPK, leading to EC apoptosis. However, auranofin at low doses
      (<=0.5 uM) specifically induces downregulation of VEGFR3 and VEGFR3-mediated EC
      proliferation and migration, two critical steps required for in vivo
      lymphangiogenesis. Mechanistically, we show that auranofin-induced VEGFR3
      downregulation is blocked by antioxidant N-acetyl-L-cysteine (NAC) and lysosome
      inhibitor chloroquine, but is promoted by proteasomal inhibitor MG132. These
      results suggest that auranofin induces VEGFR3 degradation through a lysosome
      dependent pathway. Auranofin may be a potent therapeutic agent for the treatment
      of lymphangiogenesis-dependent diseases such as lymphedema and cancer metastasis.

PMID- 24913776
TI  - A study to evaluate patterns of superficial venous reflux in patients with
      primary chronic venous disease.
AB  - OBJECTIVE: This study assessed patterns of superficial reflux in patients with
      primary chronic venous disease. METHODS: Retrospective review of all patient
      venous duplex ultrasonography reports at one institution between 2000 and 2009.
      Legs with secondary, deep or no superficial reflux were excluded. RESULTS: In
      total, 8654 limbs were scanned; 2559 legs from 2053 patients (mean age 52.3
      years) were included for analysis. Great saphenous vein reflux predominated
      (68%), followed by combined great saphenous vein/small saphenous vein reflux
      (20%) and small saphenous vein reflux (7%). The majority of legs with competent
      saphenofemoral junction had below-knee great saphenous vein reflux (53%);
      incompetent saphenofemoral junction was associated with combined above and below
      knee great saphenous vein reflux (72%). Isolated small saphenous vein reflux was
      associated with saphenopopliteal junction incompetence (61%), although the
      majority of all small saphenous vein reflux limbs had a competent
      saphenopopliteal junction (57%). CONCLUSION: Superficial venous reflux does not
      necessarily originate from a saphenous junction. Large prospective studies with
      interval duplex ultrasonography are required to unravel the natural history of
      primary chronic venous disease.

PMID- 24913777
TI  - Density-dependent habitat selection and partitioning between two sympatric
      ungulates.
AB  - Theory on density-dependent habitat selection predicts that as population density
      of a species increases, use of higher quality (primary) habitat by individuals
      declines while use of lower quality (secondary) habitat rises. Habitat
      partitioning is often considered the primary mechanism for coexistence between
      similar species, but how this process evolves with changes in population density
      remains to be empirically tested for free-ranging ungulates. We used resource
      selection functions to quantify density effects on landscape-scale habitat
      selection of two sympatric species of ungulates [moose (Alces alces) and elk
      (Cervus canadensis manitobensis)] in Riding Mountain National Park, Manitoba,
      Canada (2000-2011). The density of elk was actively reduced from 1.2 to 0.4 elk
      km(-2) through increased hunting effort during the period of study, while moose
      density decreased without additional human influence from 1.6-0.7 moose km(-2).
      Patterns of habitat selection during winter by both species changed in accordance
      to expectations from density-dependent habitat-selection theory. At low
      intraspecific density, moose and elk did not partition habitat, as both species
      selected strongly for mixed forest (primary habitat providing both food and
      cover), but did so in different areas segregated across an elevational gradient.
      As intraspecific density increased, selection for primary habitat by both species
      decreased, while selection for secondary, lower quality habitat such as
      agricultural fields (for elk) and built-up areas (for moose) increased. We show
      that habitat-selection strategies during winter for moose and elk, and subsequent
      effects on habitat partitioning, depend heavily on the position in state space
      (density) of both species.

PMID- 24913778
TI  - Comparing service use and costs among adolescents with autism spectrum disorders,
      special needs and typical development.
AB  - Autism spectrum disorder is a complex condition that requires specialised care.
      Knowledge of the costs of autism spectrum disorder, especially in comparison with
      other conditions, may be useful to galvanise policymakers and leverage investment
      in education and intervention to mitigate aspects of autism spectrum disorder
      that negatively impact individuals with the disorder and their families. This
      article describes the services and associated costs for four groups of
      individuals: adolescents with autistic disorder, adolescents with other autism
      spectrum disorders, adolescents with other special educational needs and
      typically developing adolescents using data from a large, well-characterised
      cohort assessed as part of the UK Special Needs and Autism Project at the age of
      12 years. Average total costs per participant over 6 months were highest in the
      autistic disorder group (L11,029), followed by the special educational needs
      group (L9268), the broader autism spectrum disorder group (L8968) and the
      typically developing group (L2954). Specialised day or residential schooling
      accounted for the vast majority of costs. In regression analysis, lower age and
      lower adaptive functioning were associated with higher costs in the groups with
      an autism spectrum disorder. Sex, ethnicity, number of International
      Classification of Diseases (10th revision) symptoms, autism spectrum disorder
      symptom scores and levels of mental health difficulties were not associated with
      cost. 

PMID- 24913779
TI  - Paracrine stimulation of P2X7 receptor by ATP activates a proliferative pathway
      in ovarian carcinoma cells.
AB  - P2X7 is a purinergic receptor-channel; its activation by ATP elicits a broad set
      of cellular actions, from apoptosis to signals for survival. Here, P2X7
      expression and function was studied in human ovarian carcinoma (OCA) cells, and
      biopsies from non-cancerous and cancer patients were analyzed by
      immunohistochemistry. Ovarian surface epithelium in healthy tissue expressed P2X7
      at a high level that was maintained throughout the cancer. The cell lines SKOV-3
      and CAOV-3 were used to investigate P2X7 functions in OCA. In SKOV-3 cells,
      selective stimulation of P2X7 by 2'(3')-O-(4-benzoylbenzoyl) adenosine-5'
      triphosphate (BzATP) induced a dose-dependent increase of intracellular Ca(2+)
      concentration ([Ca(2+)](i)) but not cell death. Instead, BzATP increased the
      levels of phosphorylated ERK and AKT (pERK and pAKT), with an EC(50) of 44 +/- 2
      and 1.27 +/- 0.5 MUM, respectively; 10 MUM BzATP evoked a maximum effect within
      15 min that lasted for 120 min. Interestingly, basal levels of pERK and pAKT were
      decreased in the presence of apyrase in the medium, strongly suggesting an
      endogenous, ATP-mediated phenomenon. Accordingly: (i) mechanically stimulated
      cells generated a [Ca(2+)](i) increase that was abolished by apyrase; (ii)
      apyrase induced a decrease in culture viability, as measured by the MTS assay for
      mitochondrial activity; and (iii) incubation with 10 MUM AZ10606120, a specific
      P2X7 antagonist and transfection with the dominant negative P2X7 mutant E496A,
      both reduced cell viability to 70.1 +/- 8.9% and to 76.5 +/- 5%, respectively, of
      control cultures. These observations suggested that P2X7 activity was auto
      induced through ATP efflux; this increased pERK and pAKT levels that generated a
      positive feedback on cell viability.

PMID- 24913780
TI  - History of periodontal disease diagnosis and lung cancer incidence in the Women's
      Health Initiative Observational Study.
AB  - PURPOSE: While some evidence suggests that periodontal disease (PD) might be
      positively associated with lung cancer, prospective studies in women are limited.
      Previous findings may reflect residual confounding by smoking. The study aims to
      determine whether history of PD diagnosis is associated with incident lung cancer
      in a large cohort of postmenopausal women. METHODS: Prospective analyses were
      conducted in a cohort of 77,485 postmenopausal women enrolled in the Women's
      Health Initiative Observational Study. History of PD (prevalence of 26.1 %) was
      self-reported, and 754 incident lung cancer cases occurred during an average 6.8
      (SD +/- 2.6) years of follow-up. Cox proportional hazards regression analysis was
      used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs).
      RESULTS: Overall, PD was positively associated with lung cancer risk after
      adjusting for detailed smoking history including smoking status and pack-years of
      smoking (HR 1.24, 95 % CI 1.07-1.45). There was a positive additive interaction
      between PD with pack-years of smoking (p = 0.02), suggesting a potential
      synergistic effect between PD and smoking intensity on lung cancer. The
      association between PD and lung cancer was stronger in former smokers. When
      restricted to never-smokers, PD was not associated with lung cancer (HR 1.02, 95
      % CI 0.68-1.53). CONCLUSIONS: Periodontal disease was not independently
      associated with lung cancer in non-smoking postmenopausal women. However, smoking
      and PD jointly increased lung cancer risk beyond that expected from the sum of
      the each effect separately. The potential synergism between PD and smoking on
      lung cancer warrants further examination.

PMID- 24913782
TI  - Smoking intensity and intent to continue smoking among menthol and non-menthol
      adolescent smokers in Canada.
AB  - PURPOSE: Research suggests that menthol cigarette use is associated with nicotine
      dependence. However, findings on the relationship between menthol smoking status
      and quantity of cigarettes smoked are less clear. The objective of this paper was
      to examine whether menthol cigarette smoking is associated with higher smoking
      intensity and intention to continue smoking among adolescents. METHODS: A
      nationally representative sample of 4,736 Canadian students in grades 9-12 was
      drawn from the 2010-2011 Canadian Youth Smoking Survey. Associations between
      smoking intensity and menthol smoking were examined using linear regression. A
      logistic regression was used to examine whether menthol smoking increased the
      odds that a student reported intention to continue smoking. RESULTS: Thirty-two
      percentage of smokers in grades 9-12 smoked menthol cigarettes in the last 30
      days. Unadjusted average number of cigarettes reported by menthol smokers was
      6.86 compared with 4.59 among non-menthol smokers (p < 0.001). Multivariable
      results showed that the average number of cigarettes smoked by menthol smokers
      was greater than non-menthol smokers (beta = 1.92; 95 % CI = 1.16-2.68). Similar
      results were found using the total number of cigarettes smoked in the past week.
      Additionally, menthol smokers had greater odds of reporting intent to continue
      smoking compared with non-menthol smokers (OR = 2.95; 95 % CI = 2.24-3.90). These
      results were similar when separate analyses were conducted for established
      smokers and experimental smokers. CONCLUSIONS: The findings of this study along
      with existing evidence suggest the need for banning mentholated tobacco products
      in Canada, in part because of its significant effect on adolescent smoking.

PMID- 24913781
TI  - Serum transforming growth factor-beta1 and risk of pancreatic cancer in three
      prospective cohort studies.
AB  - PURPOSE: Clinically evident chronic pancreatitis is a strong risk factor for
      pancreatic cancer. A small Japanese cohort study previously reported that pre
      diagnostic serum transforming growth factor-beta1 (TGF-beta1) concentration, a
      potential marker of subclinical pancreatic inflammation, was associated with
      higher risk of pancreatic cancer. We further explored this association in a
      larger prospective study. METHODS: Serum TGF-beta1 concentrations were measured
      in pre-diagnostic samples from 729 pancreatic cancer cases and 907 matched
      controls from a cohort of Finnish male smokers (the Alpa-Tocopherol, Beta
      Carotene (ATBC) Cancer Prevention Study) and two cohorts of US men and women, the
      Cancer Prevention Study-II and the Prostate Lung, Colorectal and Ovarian (PLCO)
      Cancer Screening Trial. Multivariable-adjusted odds ratios (ORs) were estimated
      using conditional logistic regression. RESULTS: Overall, serum TGF-beta1
      concentration was not associated with a clear increase in pancreatic cancer risk
      (OR 1.36, 95 % confidence interval (CI) 0.98-1.88 for highest vs. lowest
      quintile, p trend = 0.20). However, this association differed significantly by
      follow-up time (p = 0.02). Serum TGF-beta1 concentration was not associated with
      risk during the first 10 years of follow-up, but was associated with higher risk
      during follow-up after 10 years (OR 2.13, 95 % CI 1.23-3.68 for highest vs.
      lowest quintile, p trend = 0.001). During follow-up after 10 years, serum TGF
      beta1 was associated with higher risk only in the ATBC cohort, although most
      subjects were from ATBC during this time period and statistical evidence for
      heterogeneity across cohorts was limited (p = 0.14). CONCLUSIONS: These results
      suggest that high serum TGF-beta1 may be associated with increased risk of
      pancreatic cancer although a long follow-up period may be needed to observe this
      association.

PMID- 24913783
TI  - Roles of perceived provider cultural sensitivity and health care justice in
      African American/Black patients' satisfaction with provider.
AB  - The present study tests a refined first component of the Patient-Centered
      Culturally Sensitive Health Care (PC-CSHC) Model-the evidence supported component
      that links perceived provider cultural sensitivity to patient satisfaction with
      provider care and identifies trust of provider as the mediator of this linkage.
      The refined first component of the PC-CSHC Model tested in the present study is
      novel in that it includes the three dimensions of provider cultural sensitivity
      and includes perceived provider impartiality (fairness), a core aspect of
      perceived health care justice, as a mediator in addition to trust of provider
      (the other core aspect of perceived health care justice). Study participants were
      298 African American/Black primary care clinic patients with low household
      incomes. Mediation analyses revealed that the three dimensions of patients'
      perceived provider cultural sensitivity were significant predictors of the
      participating patients' reported satisfaction with their provider, and that some
      of these predictive relationships were partially mediated by (1) patients'
      perceived provider impartiality (fairness), and (2) patients' trust of their
      provider. Implications of these findings for providers' interactions with
      patients, development of the PC-CSHC Model, and the roles of psychologists in
      facilitating patient-provider interactions are discussed. 

PMID- 24913784
TI  - Caregiving for patients in vegetative and minimally conscious states: perceived
      burden as a mediator in caregivers' expression of needs and symptoms of
      depression and anxiety.
AB  - Involvement of family members is crucial to provide daily informal caring to
      patients in vegetative state and minimally conscious state. Previous studies
      showed that perceived burden is a risk factor for informal caregivers as it
      increases psychophysical distress. This research further investigated the
      relationship between these factors and aimed at providing a model that thoroughly
      describes this mechanism of functioning. In the frame of a national survey on
      people with disorders of consciousness, 487 informal caregivers of children and
      adult patients in vegetative and minimally conscious state were administered
      measures of depression, anxiety, caregiver needs, and family strain. Regression
      models proposed by Baron and Kenny and the Sobel test were adopted to investigate
      the relationship between depressive and anxiety symptoms, perceived burden and
      needs expressed. Our study shows that the relation between those symptoms and
      needs is mediated by burden, where higher burden accentuates and lower burden
      mitigates the needs expressed by caregivers. Our findings demonstrate that
      psychosocial components of the burden perceived by caregivers of patients with
      disorders of consciousness play a key role in shaping those caregivers' needs,
      especially their needs for information and communication. We recommend
      implementation of comprehensive steps to meet the needs of these caregivers,
      steps that incorporate improved economic and public health programs, social
      support, and use of psychological interventions to ameliorate caregivers'
      psychological distress and decrease their burden. 

PMID- 24913786
TI  - Gestational age and age at sampling influence metabolic profiles in premature
      infants.
AB  - OBJECTIVE: To describe the influence that gestational age and chronological age
      have on amino acid and acylcarnitine profiles in an at-risk population of
      premature infants. METHODS: Metabolic profiles (15 amino acids and 35
      acylcarnitines) were obtained by using standard newborn techniques on infants
      born between 23 and 31 completed weeks of gestation. The profiles were drawn
      within the first 24 hours after birth and on approximately days 7, 28, and 42 of
      life or at discharge. A single, central, contract laboratory analyzed and managed
      the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed
      with an inborn error of metabolism. Of the 3579 samples, there were 257 (7.2%)
      amino acid or acylcarnitine alerts reported in 214 infants (21.5% of infants
      studied). Both gestational age and postbirth chronological age significantly
      influenced the metabolic profile. Twenty-nine percent of infants at 23 to 26
      weeks' gestational age had an abnormal metabolic profile compared with 17% of
      infants at 29 to 31 weeks' gestational age (P < .01). On the day of birth, 12% of
      the profiles were abnormal compared with 2% on day 28 (P < .01). The highest rate
      of abnormal values occurred on day 7 in the infants 23 to 26 weeks' gestational
      age (21%). CONCLUSIONS: These results demonstrate the complexity of understanding
      the impact of immaturity and disease on metabolic profiles used to screen for
      inborn errors of metabolism. Our data provide reference values for studies aimed
      at better understanding metabolism in preterm infants.

PMID- 24913785
TI  - Screening for autism spectrum disorders: state of the art in Europe.
AB  - A large number of studies have reported on the validity of autism spectrum
      disorder (ASD) screening procedures. An overall understanding of these studies'
      findings cannot be based solely on the level of internal validity of each, since
      screening instruments might perform differently according to certain factors in
      different settings. Europe has led the field with the development of the first
      screening tool and first prospective screening study of autism. This paper seeks
      to provide an overview of ASD screening studies and ongoing programmes across
      Europe, and identify variables that have influenced the outcomes of such studies.
      Results show that, to date, over 70,000 children have been screened in Europe
      using 18 different screening procedures. Differences among findings across
      studies have enabled us to identify ten factors that may influence screening
      results. Although it is impossible to draw firm conclusions as to which screening
      procedure is most effective, this analysis might facilitate the choice of a
      screening method that best fits a specific scenario, and this, in turn, may
      eventually improve early ASD detection procedures. 

PMID- 24913787
TI  - Gross motor deficits in children prenatally exposed to alcohol: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Gross motor (GM) deficits are often reported in
      children with prenatal alcohol exposure (PAE), but their prevalence and the
      domains affected are not clear. The objective of this review was to characterize
      GM impairment in children with a diagnosis of fetal alcohol spectrum disorder
      (FASD) or "moderate" to "heavy" maternal alcohol intake. METHODS: A systematic
      review with meta-analysis was conducted. Medline, Embase, Allied and
      Complementary Medicine Database, Cumulative Index to Nursing and Allied Health
      Literature, PsycINFO, PEDro, and Google Scholar databases were searched.
      Published observational studies including children aged 0 to <=18 years with (1)
      an FASD diagnosis or moderate to heavy PAE, or a mother with confirmed alcohol
      dependency or binge drinking during pregnancy, and (2) GM outcomes obtained by
      using a standardized assessment tool. Data were extracted regarding participants,
      exposure, diagnosis, and outcomes by using a standardized protocol.
      Methodological quality was evaluated by using Strengthening the Reporting of
      Observational Studies in Epidemiology guidelines. RESULTS: The search recovered
      2881 articles of which 14 met the systematic review inclusion criteria. The
      subjects' mean age ranged from 3 days to 13 years. Study limitations included
      failure to report cutoffs for impairment, nonstandardized reporting of PAE, and
      small sample sizes. The meta-analysis pooled results (n = 10) revealed a
      significant association between a diagnosis of FASD or moderate to heavy PAE and
      GM impairment (odds ratio: 2.9; 95% confidence interval: 2.1-4.0). GM deficits
      were found in balance, coordination, and ball skills. There was insufficient data
      to determine prevalence. CONCLUSIONS: The significant results suggest evaluation
      of GM proficiency should be a standard component of multidisciplinary FASD
      diagnostic services.

PMID- 24913789
TI  - Rate of spending on chronic conditions among Medicaid and CHIP recipients.
AB  - OBJECTIVE: To evaluate the rate at which children with and without chronic
      conditions became recipients of Medicaid and the Children's Health Insurance
      Program (CHIP) during a period of economic recession and to evaluate changes in
      spending and service utilization among children with chronic conditions. METHODS:
      Child recipients of Illinois fee-for-service Medicaid and CHIP from 2007 to 2010
      were assigned to 5 chronic condition groups using 3M Clinical Risk Group
      software. Outcome measures were change in recipient number in each chronic
      condition category, total and per capita spending changes within various
      categories of service, and changes in service utilization. RESULTS: From 2007 to
      2010, children with chronic conditions became recipients of Illinois fee-for
      service Medicaid and CHIP at a higher rate than children without chronic
      conditions (26.7% vs 14.5%). Inflation-adjusted mean spending fell with a linear
      trend in all chronic condition categories except malignancy (P < .001). Per
      member inpatient and emergency department service utilization fell and outpatient
      service utilization increased in all condition categories. Average inpatient
      length of stay declined in all chronic condition groups (P < .001) but not in
      children without chronic conditions. CONCLUSIONS: From 2007 to 2010, a period of
      severe economic recession, a disproportionately high number of children with
      chronic conditions became Illinois Medicaid and CHIP recipients. Total spending
      increases were driven by an increase in the number of recipients with the most
      complex chronic conditions, not increases in per-member spending.

PMID- 24913790
TI  - An outbreak of measles in an undervaccinated community.
AB  - Measles is readily spread to susceptible individuals, but is no longer endemic in
      the United States. In March 2011, measles was confirmed in a Minnesota child
      without travel abroad. This was the first identified case-patient of an outbreak.
      An investigation was initiated to determine the source, prevent transmission, and
      examine measles-mumps-rubella (MMR) vaccine coverage in the affected community.
      Investigation and response included case-patient follow-up, post-exposure
      prophylaxis, voluntary isolation and quarantine, and early MMR vaccine for non
      immune shelter residents >6 months and <12 months of age. Vaccine coverage was
      assessed by using immunization information system records. Outreach to the
      affected community included education and support from public health, health
      care, and community and spiritual leaders. Twenty-one measles cases were
      identified. The median age was 12 months (range, 4 months to 51 years) and 14
      (67%) were hospitalized (range of stay, 2-7 days). The source was a 30-month-old
      US-born child of Somali descent infected while visiting Kenya. Measles spread in
      several settings, and over 3000 individuals were exposed. Sixteen case-patients
      were unvaccinated; 9 of the 16 were age-eligible: 7 of the 9 had safety concerns
      and 6 were of Somali descent. MMR vaccine coverage among Somali children declined
      significantly from 2004 through 2010 starting at 91.1% in 2004 and reaching 54.0%
      in 2010 (chi(2) for linear trend 553.79; P < .001). This was the largest measles
      outbreak in Minnesota in 20 years, and aggressive response likely prevented
      additional transmission. Measles outbreaks can occur if undervaccinated
      subpopulations exist. Misunderstandings about vaccine safety must be effectively
      addressed. 

PMID- 24913791
TI  - Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVE: Omega-3 long chain polyunsaturated fatty acid (LCPUFA)
      exposure can be associated with reduced neonatal morbidities. We systematically
      review the evidence for the benefits of omega-3 LCPUFAs for reducing neonatal
      morbidities in extremely preterm infants. METHODS: Data sources were PubMed,
      Embase, Center for Reviews and Dissemination, and the Cochrane Register of
      Controlled Trials. Original studies were selected that included infants born at
      <29 weeks' gestation, those published until May 2013, and those that evaluated
      the relationship between omega-3 LCPUFA supplementation and major adverse
      neonatal outcomes. Data were extracted on study design and outcome. Effect
      estimates were pooled. RESULTS: Of the 1876 studies identified, 18 randomized
      controlled trials (RCTs) and 6 observational studies met the defined criteria. No
      RCT specifically targeted a population of extremely preterm infants. Based on
      RCTs, omega-3 LCPUFA was not associated with a decreased risk of bronchopulmonary
      dysplasia in infants overall (pooled risk ratio [RR] 0.97, 95% confidence
      interval [CI] 0.82-1.13], 12 studies, n = 2809 infants); however, when
      considering RCTs that include only infants born at <=32 weeks' gestation, a trend
      toward a reduction in the risk of bronchopulmonary dysplasia (pooled RR 0.88, 95%
      CI 0.74-1.05, 7 studies, n = 1156 infants) and a reduction in the risk of
      necrotizing enterocolitis (pooled RR 0.50, 95% CI 0.23-1.10, 5 studies, n = 900
      infants) was observed with LCPUFA. CONCLUSIONS: Large-scale interventional
      studies are required to determine the clinical benefits of omega-3 LCPUFA,
      specifically in extremely preterm infants, during the neonatal period.

PMID- 24913792
TI  - Honesty, trust, and respect during consent discussions in neonatal clinical
      trials.

PMID- 24913793
TI  - Rotavirus vaccines and health care utilization for diarrhea in the United States
      (2007-2011).
AB  - OBJECTIVES: To examine reductions in diarrhea-associated health care utilization
      after rotavirus vaccine implementation and to assess direct and indirect
      effectiveness of vaccination. METHODS: Retrospective cohort analysis of claims
      data of commercially insured US children aged <5 years. We examined annual
      pentavalent (RV5) and monovalent (RV1) rotavirus vaccine coverage. We compared
      rates of diarrhea-associated health care utilization in prevaccine (2001-2006)
      versus postvaccine introduction (2007-2011) years, compared rates of diarrhea
      associated health care utilization in vaccinated versus unvaccinated children and
      compared rates in unvaccinated children in postvaccine versus prevaccine years.
      RESULTS: Among children aged <5 years, RV5 and RV1 rotavirus vaccine coverage
      rates reached 58% and 5%, respectively, by December 31, 2010. Compared with the
      average rate of rotavirus-coded hospitalizations in 2001-2006, rates were reduced
      by 75% in 2007-2008, 60% in 2008-2009, 94% in 2009-2010, and 80% in 2010-2011.
      Compared with unvaccinated children, in 2010-2011, the rate of rotavirus-coded
      hospitalizations was reduced by 92% among RV5 recipients and 96% among RV1
      recipients. Rotavirus-coded hospitalization rate reductions among RV5 recipients
      versus unvaccinated children ranged from 87% among <1-year-olds to 81% among 4
      year-olds. Compared with prevaccine rates in 2001-2006, rotavirus-coded
      hospitalization rates among unvaccinated children decreased by 50% in 2007-2008,
      77% in 2009-2010, and 25% in 2010-2011. CONCLUSIONS: Implementation of rotavirus
      vaccines has substantially reduced diarrhea health care utilization in US
      children. Both rotavirus vaccines conferred high protection against rotavirus
      hospitalizations; RV5 conferred durable protection through the fourth year of
      life. Vaccination also conferred indirect benefits to unvaccinated children.

PMID- 24913788
TI  - Association of maternal hypertension and chorioamnionitis with preterm outcomes.
AB  - OBJECTIVES: We compared the relative effect of hypertensive disorders of
      pregnancy and chorioamnionitis on adverse neonatal outcomes in very preterm
      neonates, and studied whether gestational age (GA) modulates these effects.
      METHODS: A cohort of neonates 23 to 30 weeks' GA, born in 2008 to 2011 in 82
      hospitals adhering to the Italian Neonatal Network, was analyzed. Infants born
      from mothers who had hypertensive disorders (N = 2096) were compared with those
      born after chorioamnionitis (N = 1510). Statistical analysis employed logistic
      models, adjusting for GA, hospital, and potential confounders. RESULTS: Overall
      mortality was higher after hypertension than after chorioamnionitis (odds ratio
      [OR], 1.39; 95% confidence interval [CI], 1.08-1.80), but this relationship
      changed across GA weeks; the OR for hypertension was highest at low GA, whereas
      from 28 weeks' GA onward, mortality was higher for chorioamnionitis. For other
      outcomes, the relative risks were constant across GA; infants born after
      hypertension had an increased risk for bronchopulmonary dysplasia (OR, 2.20; 95%
      CI, 1.68-2.88) and severe retinopathy of prematurity (OR, 1.48; 95% CI, 1.02
      2.15), whereas there was a lower risk for early-onset sepsis (OR, 0.25; 95% CI,
      0.19-0.34), severe intraventricular hemorrhage (OR, 0.65; 95% CI, 0.48-0.88),
      periventricular leukomalacia (OR, 0.70; 95% CI, 0.48-1.01), and surgical
      necrotizing enterocolitis or gastrointestinal perforation (OR, 0.47; 95% CI, 0.31
      0.72). CONCLUSIONS: Mortality and other adverse outcomes in very preterm infants
      depend on antecedents of preterm birth. Hypertension and chorioamnionitis are
      associated with different patterns of outcomes; for mortality, the effect changes
      across GA weeks.

PMID- 24913794
TI  - Hypertension screening using blood pressure to height ratio.
AB  - OBJECTIVES: The definition of hypertension in children is too complex to be used
      by medical professionals and children and their parents because of the age-,
      gender-, and height-specific blood pressure (BP) algorithm. The aim of this study
      was to simplify the pediatric BP percentile references using BP to height ratio
      (BPHR, equal to BP/height) for screening for prehypertension and hypertension in
      Chinese children. METHODS: Data were obtained from the China Health and Nutrition
      Survey, which was conducted from 1991 to 2009 and included 11 661 children aged 6
      to 17 years with complete data on age, gender, height, and BP values. Receiver
      operating characteristic curve analysis was performed to assess the performance
      of systolic BPHR (SBPHR) and diastolic BPHR (DBPHR) for screening for pediatric
      prehypertension and hypertension. RESULTS: The optimal thresholds for defining
      prehypertension were 0.81 in children aged 6 to 11 years and 0.70 in adolescents
      aged 12 to 17 years for SBPHR and 0.52 in children and 0.46 in adolescents for
      DBPHR, respectively. The corresponding values for hypertension were 0.84, 0.78,
      0.55, and 0.50, respectively. The negative predictive values were much higher
      (all >=99%) for prehypertension and hypertension, although the positive
      predictive values were relatively lower, ranging from 13% to 75%. CONCLUSIONS:
      BPHR index is simple and accurate for screening for prehypertension and
      hypertension in Chinese children aged 6 to 17 years and can be used for early
      screening or treating Chinese children with hypertension.

PMID- 24913795
TI  - Stridor in asphyxiated neonates undergoing therapeutic hypothermia.
AB  - Therapeutic hypothermia is an established standard of care in the treatment of
      hypoxic-ischemic encephalopathy. Application of therapeutic hypothermia in the
      clinical setting may reveal a wider spectrum of adverse events than previously
      reported. We report 5 cases of transient respiratory stridor in 51 infants,
      occurring at different time points in the cooling process, which appeared to be
      unrelated to the intubation procedure. Therapeutic hypothermia was associated
      with transient stridor in this case series. Formal laryngoscopy is required to
      determine the underlying pathologic etiology. 

PMID- 24913796
TI  - Impact of vaccination on the epidemiology of varicella: 1995-2009.
AB  - BACKGROUND: When varicella vaccine was licensed in the United States in 1995,
      there were concerns that childhood vaccination might increase the number of
      adolescents susceptible to varicella and shift disease toward older age groups
      where it can be more severe. METHODS: We conducted a series of 5 cross-sectional
      studies in 1994 to 1995 (prevaccine), 2000, 2003, 2006, and 2009 in Kaiser
      Permanente of Northern California to assess changes in varicella epidemiology in
      children and adolescents, as well as changes in varicella hospitalization in
      people of all ages. For each study, information on varicella history and
      varicella occurrence during the past year was obtained by telephone survey from a
      sample of ~8000 members 5 to 19 years old; varicella hospitalization rates were
      calculated for the entire membership. RESULTS: Between 1995 and 2009, the overall
      incidence of varicella in 5- to 19-year-olds decreased from 25.8 to 1.3 per 1000
      person-years, a ~90% to 95% decline in the various age categories (5-9, 10-14,
      and 15-19 years of age). The proportion of varicella-susceptible children and
      adolescents also decreased in all age groups, including in 15- to 19-year-olds
      (from 15.6% in 1995 to 7.6% in 2009). From 1994 to 2009, age-adjusted varicella
      hospitalization rates in the general member population decreased from 2.13 to
      0.25 per 100,000, a ~90% decline. CONCLUSIONS: In the 15 years after the
      introduction of varicella vaccine, a major reduction in varicella incidence and
      hospitalization was observed with no evidence of a shift in the burden of
      varicella to older age groups.

PMID- 24913797
TI  - Need for a working classification system for sudden and unexpected infant deaths.

PMID- 24913798
TI  - Classification system for the Sudden Unexpected Infant Death Case Registry and
      its application.
AB  - Sudden unexpected infant deaths (SUID) accounted for 1 in 3 postneonatal deaths
      in 2010. Sudden infant death syndrome and accidental sleep-related suffocation
      are among the most frequently reported types of SUID. The causes of these SUID
      usually are not obvious before a medico-legal investigation and may remain
      unexplained even after investigation. Lack of consistent investigation practices
      and an autopsy marker make it difficult to distinguish sudden infant death
      syndrome from other SUID. Standardized categories might assist in differentiating
      SUID subtypes and allow for more accurate monitoring of the magnitude of SUID, as
      well as an enhanced ability to characterize the highest risk groups. To capture
      information about the extent to which cases are thoroughly investigated and how
      factors like unsafe sleep may contribute to deaths, CDC created a multistate SUID
      Case Registry in 2009. As part of the registry, the Centers for Disease Control
      and Prevention developed a classification system that recognizes the uncertainty
      about how suffocation or asphyxiation may contribute to death and that accounts
      for unknown and incomplete information about the death scene and autopsy. This
      report describes the classification system, including its definitions and
      decision-making algorithm, and applies the system to 436 US SUID cases that
      occurred in 2011 and were reported to the registry. These categories, although
      not replacing official cause-of-death determinations, allow local and state
      programs to track SUID subtypes, creating a valuable tool to identify gaps in
      investigation and inform SUID reduction strategies. 

PMID- 24913799
TI  - Acquired resistance to EGFR-targeted therapies in colorectal cancer.
AB  - Cetuximab and panitumumab are anti-epidermal growth factor receptor (anti-EGFR)
      monoclonal antibodies used as therapies for metastatic colorectal cancer
      patients. Intrinsic mechanisms of resistance, such as RAS mutations, can prevent
      patients from having a response with clinical benefit. The clinical efficacy of
      EGFR targeted antibodies is limited by the development of acquired (secondary)
      resistance, which typically occurs within 3-12 months from the start of therapy.
      Preclinical models and analyses of clinical samples have uncovered some of the
      alterations that confer a selective advantage to tumor cells when under the
      pressure of anti-EGFR therapy. Molecular profiling of clinical specimens
      confirmed that genetic alterations of genes in the EGFR-RAS-RAF-MEK signaling
      pathway and of receptor tyrosine kinases are mechanisms of acquired resistance to
      anti-EGFR antibodies. The escape from anti-EGFR blockade appears to converge on
      the (re)activation of MEK-ERK or AKT as revealed in preclinical studies.
      Circulating tumor DNA and patient derived xenografts have proven useful tools to
      monitor patients for resistance to anti-EGFR therapy and test combination
      therapies to overcome or reverse resistance. 

PMID- 24913800
TI  - Genetic diversity influences the response of the brain to developmental lead
      exposure.
AB  - Although extrinsic factors, such as nutritional status, and some intrinsic
      genetic factors may modify susceptibility to developmental lead (Pb) poisoning,
      no studies have specifically examined the influence of genetic background on
      outcomes from Pb exposure. In this study, we used gene microarray profiling to
      identify Pb-responsive genes in rats of different genetic backgrounds, including
      inbred (Fischer 344 (F344)) and outbred (Long Evans (LE), Sprague Dawley (SD))
      strains, to investigate the role that genetic variation may play in influencing
      outcomes from developmental Pb exposure. Male and female animals received either
      perinatal (gestation through lactation) or postnatal (birth through weaning)
      exposure to Pb in food (0, 250, or 750 ppm). RNA was extracted from the
      hippocampus at day 55 and hybridized to Affymetrix Rat Gene 1.0 ST Arrays. There
      were significant strain-specific effects of Pb on the hippocampal transcriptome
      with 978 transcripts differentially expressed in LE rats across all experimental
      groups, 269 transcripts differentially expressed in F344 rats, and only 179
      transcripts differentially expressed in SD rats. These results were not due to
      strain-related differences in brain accumulation of Pb. Further, no genes were
      consistently differentially regulated in all experimental conditions. There was
      no set of "Pb toxicity" genes that are a molecular signature for Pb neurotoxicity
      that transcended sex, exposure condition, and strain. These results demonstrate
      the influence that strain and genetic background play in modifying the brain's
      response to developmental Pb exposure and may have relevance for better
      understanding the molecular underpinnings of the lack of a neurobehavioral
      signature in childhood Pb poisoning. 

PMID- 24913801
TI  - Keto amphetamine toxicity-focus on the redox reactivity of the cathinone designer
      drug mephedrone.
AB  - The beta-keto amphetamine (cathinone, beta-KA) designer drugs such as mephedrone
      (4-methylmethcathinone, 4-MMC) show a large degree of structural similarity to
      amphetamines like methamphetamine (METH). However, little is currently known
      about whether these substances also share the potential neurotoxic properties of
      their non-keto amphetamine counterparts, or what mechanisms could be involved.
      Here, we evaluate the cytotoxicity of beta-KAs in SH-SY5Y cells using lactate
      dehydrogenase (LDH) assays, assess the redox potential of a range of beta-KAs and
      non-keto amphetamines using the sensitive redox indicator 2-(4-Iodophenyl)-3-(4
      nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1), and explore the effect
      of 4-MMC on the formation of protein adducts using ultra-high performance liquid
      chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS)
      and on the mitochondrial respiratory chain using high-resolution respirometry. We
      show that treatment with beta-KAs increases LDH release. Further, we demonstrate
      that even under physiological pH, beta-KAs are effective and selective-as
      compared with their non-keto analogues-reductants in the presence of electron
      acceptors. Increased pH (range 7.6-8.0) greatly enhanced the reactivity up to
      sixfold. We found no evidence of protein adduct formation, suggesting the
      reactivity is due to direct electron transfer by the beta-KAs. Finally, we show
      that 4-MMC and METH produce dissimilar effects on the respiratory chain. Our
      results indicate that beta-KAs such as 4-MMC possess cytotoxic properties in
      vitro. Furthermore, in the presence of an electron-accepting redox partner, the
      ketone moiety of beta-KAs is vital for pH-dependent redox reactivity. Further
      work is needed to establish the importance of beta-KA redox properties and its
      potential toxicological importance in vivo. 

PMID- 24913802
TI  - Inhibition of voltage-gated calcium channels as common mode of action for
      (mixtures of) distinct classes of insecticides.
AB  - Humans are exposed to distinct structural classes of insecticides with different
      neurotoxic modes of action. Because calcium homeostasis is essential for proper
      neuronal function and development, we investigated the effects of insecticides
      from different classes (pyrethroid: (alpha-)cypermethrin; organophosphate:
      chlorpyrifos; organochlorine: endosulfan; neonicotinoid: imidacloprid) and
      mixtures thereof on the intracellular calcium concentration ([Ca(2+)]i). Effects
      of acute (20 min) exposure to (mixtures of) insecticides on basal and
      depolarization-evoked [Ca(2+)]i were studied in vitro with Fura-2-loaded PC12
      cells and high resolution single-cell fluorescence microscopy. The data
      demonstrate that cypermethrin, alpha-cypermethrin, endosulfan, and chlorpyrifos
      concentration-dependently decreased depolarization-evoked [Ca(2+)]i, with 50%
      (IC50) at 78nM, 239nM, 250nM, and 899nM, respectively. Additionally, acute
      exposure to chlorpyrifos or endosulfan (10MUM) induced a modest increase in basal
      [Ca(2+)]i, amounting to 68 +/- 8nM and 53 +/- 8nM, respectively. Imidacloprid did
      not disturb basal or depolarization-evoked [Ca(2+)]i at 10MUM. Following exposure
      to binary mixtures, effects on depolarization-evoked [Ca(2+)]i were within the
      expected effect additivity range, whereas the effect of the tertiary mixture was
      less than this expected additivity effect range. These results demonstrate that
      different types of insecticides inhibit depolarization-evoked [Ca(2+)]i in PC12
      cells by inhibiting voltage-gated calcium channels (VGCCs) in vitro at
      concentrations comparable with human occupational exposure levels. Moreover, the
      effective concentrations in this study are below those for earlier described
      modes of action. Because inhibition of VGCCs appears to be a common and
      potentially additive mode of action of several classes of insecticides, this
      target should be considered in neurotoxicity risk assessment studies. 

PMID- 24913803
TI  - Gestational and lactational exposure to atrazine via the drinking water causes
      specific behavioral deficits and selectively alters monoaminergic systems in
      C57BL/6 mouse dams, juvenile and adult offspring.
AB  - Atrazine (ATR) is one of the most frequently detected pesticides in the U.S.
      water supply. This study aimed to investigate neurobehavioral and neurochemical
      effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3
      mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water
      (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included
      open field, pole, grip strength, novel object recognition (NOR), forced swim, and
      marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body
      or brain weights were not affected by ATR. However, ATR-treated dams exhibited
      decreased NOR performance and a trend toward hyperactivity. Juvenile offspring
      (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time
      swimming (males), and buried more marbles (females). In adult offspring (PND70),
      the only behavioral change was a sex-specific (females) decreased NOR performance
      by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams
      and a significant increase in juvenile offspring (both sexes) was observed.
      Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult
      female offspring. These results suggest that perinatal DW exposure to ATR targets
      the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters
      dams' cognitive performance, induces sex-selective changes involving motor and
      emotional functions in juvenile offspring, and decreases cognitive ability of
      adult female offspring, with the latter possibly associated with altered
      perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation
      and lactation may cause adverse nervous system effects to both offspring and
      dams. 

PMID- 24913804
TI  - Tissue-specific effects of valproic acid on DNA repair genes and apoptosis in
      postimplantation mouse embryos.
AB  - Exposure to the anticonvulsant drug valproic acid (VPA) is associated with an
      increased risk of congenital malformations. Although the mechanisms contributing
      to its teratogenicity are poorly understood, VPA has been shown to induce DNA
      double strand breaks (DSB) and to increase homologous recombination in vitro. The
      objective of the present study was to determine whether in utero exposure to VPA
      alters the frequency of intrachromosomal recombination and the expression of
      several genes involved in DSB repair in pKZ1 mouse embryos. Pregnant pKZ1
      transgenic mice (GD 9.0) were administered VPA (500 mg/kg s.c.) and embryos were
      extracted and microdissected into the head, heart, and trunk regions 1, 3, 6, and
      24 h after injection. Quantitative PCR was used to measure the tissue-specific
      expression of lacZ, a surrogate measure of recombination, Xrcc4, Rad51, Brca1,
      and Brca2, with Western blotting used to quantify Rad51, cleaved caspase-3 and
      cleaved-PARP protein. Increased recombination was only observed in the embryonic
      head following 6-h VPA exposure. VPA had no effect on Xrcc4 expression. Rad51,
      Brca1, and Brca2 expression rapidly decreased in head and trunk tissues after 1-h
      VPA exposure, followed by a subsequent increase in all tissues, although it was
      generally attenuated in the head and not due to differences in endogenous levels.
      Cleaved caspase-3 and cleaved-PARP expression was increased in all tissues 3 h
      following VPA exposure. This study indicates that the tissue-specific expression
      of several genes involved in DSB repair is altered following exposure to VPA and
      may be contributing to increased apoptosis. 

PMID- 24913805
TI  - The Drosophila lingerer protein cooperates with Orb2 in long-term memory
      formation.
AB  - Recently mated Drosophila females were shown to be reluctant to copulate and to
      exhibit rejecting behavior when courted by a male. Males that experience mate
      refusal by a mated female subsequently attenuate their courtship effort toward
      not only mated females but also virgin females. This courtship suppression
      persists for more than a day, and thus represents long-term memory. The courtship
      long-term memory has been shown to be impaired in heterozygotes as well as
      homozygotes of mutants in orb2, a locus encoding a set of CPEB RNA-binding
      proteins. We show that the impaired courtship long-term memory in orb2-mutant
      heterozygotes is restored by reducing the activity of lig, another putative RNA
      binding protein gene, yet on its own the loss-of-function lig mutation is without
      effect. We further show that Lig forms a complex with Orb2. We infer that a
      reduction in the Lig levels compensates the Orb2 deficiency by mitigating the
      negative feedback for Orb2 expression and thereby alleviating defects in long
      term memory.

PMID- 24913806
TI  - Correlation between OPN gene polymorphisms and the risk of nasopharyngeal
      carcinoma.
AB  - Previous studies suggest that osteopontin (OPN) levels are associated with the
      incidence and development of multiple types of cancer. This study analyzes the
      correlation between OPN gene variants and nasopharyngeal carcinoma (NPC). A total
      of 150 NPC patients and 150 healthy adults were enrolled and divided into NPC and
      control groups. In both groups, four OPN polymorphisms including rs1126772,
      rs4754, rs11728697 and rs9138 were quantitatively genotyped by SNaPshot SNP
      genotyping assay. Allele frequencies of four OPN polymorphisms were compared
      between two groups. No statistical significance was noted regarding genotype
      frequency of four OPN polymorphisms between male NPC and healthy subjects (all P
      > 0.05). Female subjects between two groups significantly differed in terms of
      genotype frequency of rs1172869 (P = 0.002). No statistical significance was
      observed in allele frequencies in each of four OPN polymorphisms between two
      groups (all P > 0.05). For NPC patients, the polymorphisms information content
      (PIC) ranged from 0.2961 to 0.3584 and 0.3047 to 0.3655 for normal controls.
      Additionally, rs11728697 had the highest effective number of alleles (Ne),
      expected heterozygosity (HE) and PIC in two groups. Female subjects in two groups
      significantly differed in the genotype frequency of rs1172869 while no
      statistical significance was noted for male counterparts. All subjects in the NPC
      and control groups had similar allele frequency. All the four OPN polymorphisms
      were moderately polymorphic. The mean NA, Ne, Ho, He and PIC of each OPN
      polymorphism in the control group were higher than those in the NPC group without
      a significant difference.

PMID- 24913807
TI  - Multidriver mutation analysis in pulmonary mucinous adenocarcinoma in Taiwan:
      identification of a rare CD74-NRG1 translocation case.
AB  - Several new chromosomal translocations resulting in driver fusion mutations have
      recently been discovered in non-small-cell lung cancer. The driver mutational
      patterns in pulmonary mucinous adenocarcinoma, a rare subtype of non-small-cell
      lung cancer, have not been well studied. A single-institute cohort study in
      Taiwan was performed to determine the mutations of epidermal growth factor
      receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), fusions of
      anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and neuregulin 1
      (NRG1) in patients diagnosed with pulmonary mucinous adenocarcinoma. We also
      examined NRG1 translocation in patients diagnosed as adenocarcinoma of other
      subtypes with wild-type EGFR, KRAS, ALK, and ROS1 genes. Surgical or biopsy
      specimens were collected from 13 patients with mucinous adenocarcinoma. Using the
      direct RNA sequencing method, we discovered a rare CD74-NRG1 fusion (8 %), an
      echinoderm microtubule-associated protein like 4 (EML4)-ALK fusion (17 %), and
      three KRAS mutations (25 %). No EGFR mutations or ROS1 rearrangements were
      detected. The rare CD74-NRG1 fusion positive patient presented with uncommon
      radiological features. We did not detect any CD74-NRG1 fusion in the 109
      adenocarcinoma of other subtypes, which were all negative for EGFR, KRAS, ALK,
      and ROS1. The CD74-NRG1 fusion mutation is rare and may be exclusively present in
      patients with pulmonary mucinous adenocarcinoma. Patients harboring CD74-NRG1
      positive tumors may present with uncommon imaging features.

PMID- 24913808
TI  - Sexual satisfaction, anxiety, depression and quality of life in testicular cancer
      survivors.
AB  - We aimed to investigate anxiety, depression and sexual satisfaction levels of
      testicular cancer survivors (TCSs) and compare the scores with healthy men's. The
      Hospital Anxiety and Depression Scale (HADS), Golombok-Rust Inventory of Sexual
      Satisfaction (GRISS) and European Organization for Research on Treatment of
      Cancer Questionnaires Quality of Life-C30 were used. Forty-one TCSs and thirty
      eight healthy men were participated in this study. The total HADs scores of TCSs
      (12.21 +/- 8.19) were less than the healthy group (14.44 +/- 6.53; p > 0.05). The
      high depression scores rate was 29.2 and 55.2, and high anxiety scores rate was
      24.4 and 28.9 for TCSs and healthy group, respectively. When we evaluated GRISS
      subscores and anxiety levels, we found significantly increase only in avoidance
      subscores in the TCSs (p = 0.04). When we evaluated GRISS subscores and
      depression levels, GRISS subscores of the TCSs who had high depression scores
      were also high. However, statistical significance was found in satisfaction (p =
      0.009), touch (p = 0.04), avoidance (p = 0.01) and erectile dysfunction (p =
      0.04) subscores in the TCSs. In the TCSs whose anxiety scores were high,
      emotional functioning (p = 0.009) and global QoL (p = 0.01) subscores of GRISS
      was found significantly low. In the TCSs whose depression scores were high,
      physical (p = 0.01), cognitive (p = 0.04), emotional (p = 0.03), social
      functioning (p = 0.02) and global QoL (p < 0.001) subscores of GRISS were found
      significantly low. Anxiety, depression and sexual satisfaction levels of TCSs
      were found to be similar with the control population.

PMID- 24913809
TI  - Optimal timing of hormonal therapy for prostate-specific antigen recurrence after
      radical prostatectomy.
AB  - The present study was undertaken to examine biochemical progression in patients
      who received salvage hormonal therapy (HT) for biochemical disease recurrence
      (BCR) after radical prostatectomy (RP), and to determine the optimal timing for
      the administration of HT. The study population consisted of 156 patients who
      underwent RP and received salvage HT for BCR. The starting point of this study
      was the timing of RP, and the endpoint was biochemical prostate-specific antigen
      (PSA) progression (castration-resistance) after HT. The mean follow-up period
      after surgery was 8.1 years. First, we excluded 18 patients with persistent PSA
      (>= 0.2 ng/mL) after RP from an analysis below because their prognoses were
      significantly poorer compared with 138 patients whose PSA nadirs had reached <0.2
      ng/mL. Multivariate analysis demonstrated that Gleason score >= 8 (p = 0.010,
      hazard ratio (HR) 3.02), and PSA doubling time (PSA-DT) <6 months (p = 0.001, HR
      7.39) was independently associated with subsequent biochemical progression after
      HT. Using these two variables (Gleason score and PSA-DT), we could stratify
      patients into three risk groups for BCR after salvage HT. Regarding the optimal
      timing for HT administration for these high-risk patients with both risk factors
      (relative risk = 22.3), the PSA cutpoint of 1.0 ng/mL at the initiation of HT
      showed a significant difference in progression-free survival rates (p = 0.023).
      The findings indicated that for high-risk patients, salvage HT for BCR after PSA
      nadir (<0.2 ng/mL) should be started before the PSA level exceeds 1.0 ng/mL;
      otherwise, there is a significant risk of subsequent biochemical progression
      after HT.

PMID- 24913810
TI  - Is there a role for second-line platinum re-challenge in advanced biliary tract
      cancers?
AB  - The clinical benefit of second-line chemotherapy in advanced biliary tract
      cancers is currently unknown. We investigated the role of platinum re-challenge
      in a selected cohort of patients who progressed after first-line
      gemcitabine/cisplatin (GemCis) chemotherapy. We retrospectively analysed seventy
      four patients treated between January 2008 and September 2012 at Nottingham
      University Hospitals. Demographics, treatment data, radiological response and
      survival data were captured. Univariate and multivariate analysis of survival
      outcomes were evaluated. Platinum sensitive disease was defined as tumours that
      progress after 12 weeks of completion of first-line GemCis chemotherapy. Seventy
      four patients (median age = 67 years) had received first-line chemotherapy
      (gemcitabine alone = 21/74, Gem/Cis combination = 53/74). Best response to GemCis
      chemotherapy was as follows; partial response (PR) (17 %), stabilisation of
      disease (SD) (39.6 %), disease control rate (DCR) (56.6 %) and disease
      progression (43.4 %). 18/74 patients received second-line chemotherapy [GemCis
      (12/18), 5-FU/cisplatin (4/18), gemcitabine (2/8)]. Best response to GemCis
      second-line chemotherapy was as follows: PR (33.3 %), SD (33.3 %) and DCR (66.6
      %). The median overall survival in patients who received second-line chemotherapy
      was 29 months compared to 10.6 months in patients who received first-line therapy
      only (p = 0.00001). The data suggest that patients who progress after 12 weeks of
      completion of first-line therapy may remain platinum sensitive and benefit from
      second-line platinum re-challenge. Prospective multicentre studies are warranted
      to explore this possibility further.

PMID- 24913811
TI  - Effect of interaction of glutathione S-transferases (T1 and M1) on the
      hematologic and cytogenetic responses in chronic myeloid leukemia patients
      treated with imatinib.
AB  - The glutathione S-transferases (GSTs) are phase II xenobiotic metabolizing
      enzymes known to be involved in the detoxification of carcinogens and anticancer
      drugs. Individual genetic variation linked to inherited polymorphisms of GSTT1
      and GSTM1 leading to a complete loss of enzyme activity could expose subjects to
      develop cancer or to induce drug resistance. Indeed, despite the impressive
      results obtained with the imatinib, some patients with chronic myeloid leukemia
      (CML) fail to achieve the expected results or develop resistance. The present
      study aimed to examine the impact of GSTT1 and GSTM1 polymorphisms on the
      response to imatinib in patients with CML. Multiplex polymerase chain reaction
      was used to detect the genotypes of GSTT1 and GSTM1 in 60 CML patients. We found
      that side effects were more frequent in patients carrying GSTT1 null when
      compared to GSTT1 present carriers (31 vs. 16.6 %; chi (2) = 6.2; p = 0.013). The
      loss of hematologic response was statistically greater in patients carrying the
      combined genotype GSTT1 present/GSTM1 present (26.3 %) when compared to GSTT1
      null/GSTM1 present (12.8 %), GSTT1 present/GSTM1 null (8.3 %) and GSTT1
      null/GSTM1 null (0 %), (chi (2) = 18.85; p < 0.001). The complete cytogenetic
      response was higher in patients harboring the GSTT1 null/GSTM1 null (75 %)
      compared with GSTT1 null/GSTM1 present (55.6 %), GSTT1 present/GSTM1 null (50 %)
      and GSTT1 present/GSTM1 present (47.8). On the other hand, the frequency of none
      cytogenetic responders was more common in patients carrying GSTT1 present/GSTM1
      present (34.8 %) when compared to other genotype combinations (chi (2) = 20.99; p
      = 0.05). Moreover, the GSTT1 present/GSTM1 present appeared to be associated with
      a final dose of 600 or 800 mg of imatinib, but not significantly. Based on these
      findings, we find that the interaction between GSTT1 and GSTM1 seems to influence
      treatment outcome in patients with CML. Therefore, further investigations are
      required to confirm these results, for better genotype-phenotype correlation.

PMID- 24913812
TI  - Serum CA125 level predicts prognosis in patients with multiple brain metastases
      from non-small cell lung cancer before and after treatment of whole-brain
      radiotherapy.
AB  - This study was to evaluate the effect of serum CA125 level on the prognosis of
      patients with multiple brain metastases from non-small cell lung cancer before
      and after treatment of whole-brain radiotherapy. Sixty-six patients with multiple
      brain metastases from non-small cell lung cancer before and after treatment of
      radiotherapy were reviewed retrospectively. Radiotherapy was given to the whole
      brain using opposed 6MV lateral beams with a dose of 30 Gy in 15 fractions in 3
      weeks. Elevated CA125 was defined as >35 U/mL. The survival rate was calculated
      using the Kaplan-Meier method, and the univariate and multivariate analyses were
      used to identify significant factors associated with prognosis, using a Cox
      proportional hazards model. During the median (range) follow-up of 1.25 (0.25
      2.50) years, 62 patients died from non-small cell lung cancer; the 1-year cancer
      specific survival (CSS) rate was 43.08 %. Thirty patients had a high CA125 level
      before chemoradiotherapy (>35U/mL), and their CSS rate was significantly worse
      than that in the remaining patients (P = 0.024). Multivariate analysis showed
      that CA125 level, number of metastases and total tumor volume were independent
      prognostic indicators for CSS, with a hazard ratio of 1.99, 1.67 and 2.02,
      respectively. The elevation of CA125 before treatment predicts a poor prognosis
      in patients with multiple brain metastases from non-small cell lung cancer before
      and after treatment of whole-brain radiotherapy.

PMID- 24913813
TI  - Decreased ITIH5 expression is associated with poor prognosis in primary gastric
      cancer.
AB  - Inter-alpha-trypsin inhibitors (ITIs) are a family of serine protease inhibitors
      that comprise one light chain and a variable set of heavy chains (ITI heavy
      chains, ITIHs). ITIH5 is a new member of the ITIH family that contains two
      domains conserved in all known ITIHs: vault protein IT and von Willebrand type A.
      Recent studies suggest that ITIH5 expression may be altered in certain types of
      cancer. This study aimed to investigate ITIH5 expression in clinical tumor
      specimens from gastric cancer patients and its prognostic value for gastric
      cancer. ITIH5 expression was detected in fresh gastric cancer tissues (T) and the
      matched adjacent non-tumor tissues (ANT) using real-time quantitative reverse
      transcription-PCR and Western blotting. ITIH5 expression was retrospectively
      detected in 331 paraffin-embedded, banked samples using immunohistochemical
      staining. ITIH5 mRNA and protein expression was significantly downregulated in
      gastric cancer tissues compared to the ANT. There was a significant association
      between ITIH5 expression and histological grade (P = 0.020), N classification (P
      = 0.047), and clinical stage (P = 0.011). Patients with low ITIH5 expression had
      shorter survival compared to those with high ITIH5 expression. Multivariate
      analysis showed that ITIH5 expression was an independent prognostic factor for
      overall survival of gastric cancer patients (P = 0.034). Our data suggest that
      ITIH5 could play an important role in gastric cancer and may serve as a valuable
      prognostic biomarker and potential molecular therapy target for gastric cancer.

PMID- 24913814
TI  - Spatial memory alterations in children with epilepsy of genetic origin or unknown
      cause.
AB  - Genetic generalised epilepsy or epilepsy of unknown cause can remit before
      adolescence. In many children, the disease does not interfere with their academic
      achievement. Although there are neuropsychological studies characterising the
      cognitive profile, there are no studies in this population focused on spatial
      orientation abilities. In this study, we compared children with genetic
      generalised epilepsy or epilepsy of unknown cause with a control group using a
      virtual spatial learning task. Children with epilepsy showed worse performance on
      the spatial orientation task, although their visuo-spatial memory, attention, and
      working memory were normal. These results confirm that genetic generalised
      epilepsy or epilepsy of unknown cause is associated with more cognitive deficits.
      Virtual reality technologies can complement clinical assessment. 

PMID- 24913815
TI  - Spectroscopic and molecular simulation studies on the interaction of di-(2
      ethylhexyl) phthalate and human serum albumin.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in industrial
      production, but may have a potential health risk. In this study, the binding
      characteristics of DEHP with human serum albumin (HSA) in aqueous solution at pH
      7.4 were determined using UV/vis absorption, fluorescence, Fourier transform
      infrared (FTIR) spectroscopy and circular dichroism (CD), along with a molecular
      simulation technique. Analysis of the fluorescence titration data at different
      temperatures suggested that the fluorescence quenching mechanism of HSA by DEHP
      was static. The calculated thermodynamic parameters indicated that hydrophobic
      forces played a predominant role in formation of the DEHP-HSA complex, but
      hydrogen bonds could not be omitted. Site marker competitive experiments and
      denaturation studies showed that the binding of DEHP to HSA primarily took place
      in subdomain IIA of HSA, and molecular docking results further corroborated the
      binding sites. The synchronous fluorescence, UV/vis absorption, FTIR and CD
      spectra revealed that the addition of DEHP induced changes in the secondary
      structure of HSA. Protein surface hydrophobicity (PSH) tests indicated that DEHP
      binding to HSA caused an increase in the PSH. Moreover, the effects of some metal
      ions on the binding constant of DEHP - HSA interaction were also investigated.

PMID- 24913816
TI  - Digital panoramic radiographs are useful for diagnosis of osteoporosis in Korean
      postmenopausal women.
AB  - OBJECTIVE: The purpose of this study was to determine whether digital panoramic
      radiographs could be used for the diagnosis of osteoporosis through evaluation of
      the radiographs based on the correlation with bone mineral density (BMD).
      METHODS: One hundred and ninety-four post-menopausal women were selected from
      participants who had participated in the Dong-gu study. Panoramic radiographic
      indices measured are mental index (MI), mandibular cortical index (MCI) and
      simple visual estimation (SVE). BMD at the lumbar spine and proximal femur was
      measured by dual-energy X-ray absorptiometry (DXA). The Pearson's correlation
      test was performed to analyse the correlation between MI and age and BMD at the
      lumbar spine, femoral neck and total hip. Multiple linear regression analysis was
      performed to analyse the association of MI, MCI and SVE with BMD after adjusting
      for age, height and weight. To determine the optimal cut-off point of MI for the
      diagnosis of osteoporosis, the receiver operating characteristic analysis was
      performed. RESULTS: The MI was positively correlated with BMDs: lumbar spine: r =
      0.36, femoral neck: r = 0.59 and total hip: r = 0.58 (p < 0.001). As age
      increased, MI decreased (r = -0.46). BMD at the lumbar spine and total hip were
      significantly lower in participants with reduction of mandibular width, thinning
      and resorption of mandibular cortex by the MI, SVE and MCI, respectively. The
      optimal cut-off value of MI for the diagnosis of spinal osteoporosis was 2.22 mm.
      CONCLUSION: Thickness and morphological changes of mandibular inferior cortical
      bone are associated with BMD, independent of age, height and weight. These
      results suggest that MI, MCI and SVE may be useful indices for the diagnosis of
      osteoporosis in a Korean population.

PMID- 24913817
TI  - Loss of miR125a expression in a model of K-ras-dependent pulmonary premalignancy.
AB  - Understanding the molecular pathogenesis of lung cancer is necessary to identify
      biomarkers/targets specific to individual airway molecular profiles and to
      identify options for targeted chemoprevention. Herein, we identify mechanisms by
      which loss of microRNA (miRNA)125a-3p (miR125a) contributes to the malignant
      potential of human bronchial epithelial cells (HBEC) harboring an activating
      point mutation of the K-ras proto-oncogene (HBEC K-ras). Among other miRNAs, we
      identified significant miR125a loss in HBEC K-ras lines and determined that
      miR125a is regulated by the PEA3 transcription factor. PEA3 is upregulated in
      HBEC K-ras cells, and genetic knockdown of PEA3 restores miR125a expression. From
      a panel of inflammatory/angiogenic factors, we identified increased CXCL1 and
      vascular endothelial growth factor (VEGF) production by HBEC K-ras cells and
      determined that miR125a overexpression significantly reduces K-ras-mediated
      production of these tumorigenic factors. miR125a overexpression also abrogates
      increased proliferation of HBEC K-ras cells and suppresses anchorage-independent
      growth (AIG) of HBEC K-ras/P53 cells, the latter of which is CXCL1-dependent.
      Finally, pioglitazone increases levels of miR125a in HBEC K-ras cells via PEA3
      downregulation. In addition, pioglitazone and miR125a overexpression elicit
      similar phenotypic responses, including suppression of both proliferation and
      VEGF production. Our findings implicate miR125a loss in lung carcinogenesis and
      lay the groundwork for future studies to determine whether miR125a is a possible
      biomarker for lung carcinogenesis and/or a chemoprevention target. Moreover, our
      studies illustrate that pharmacologic augmentation of miR125a in K-ras-mutated
      pulmonary epithelium effectively abrogates several deleterious downstream events
      associated with the mutation.

PMID- 24913819
TI  - Exploring the evidence for early unclamping during robot-assisted partial
      nephrectomy: is it worth the time and effort?

PMID- 24913818
TI  - Rapid and sustainable detoxication of airborne pollutants by broccoli sprout
      beverage: results of a randomized clinical trial in China.
AB  - Broccoli sprouts are a convenient and rich source of the glucosinolate,
      glucoraphanin, which can generate the chemopreventive agent, sulforaphane, an
      inducer of glutathione S-transferases (GST) and other cytoprotective enzymes. A
      broccoli sprout-derived beverage providing daily doses of 600 MUmol glucoraphanin
      and 40 MUmol sulforaphane was evaluated for magnitude and duration of
      pharmacodynamic action in a 12-week randomized clinical trial. Two hundred and
      ninety-one study participants were recruited from the rural He-He Township,
      Qidong, in the Yangtze River delta region of China, an area characterized by
      exposures to substantial levels of airborne pollutants. Exposure to air pollution
      has been associated with lung cancer and cardiopulmonary diseases. Urinary
      excretion of the mercapturic acids of the pollutants, benzene, acrolein, and
      crotonaldehyde, were measured before and during the intervention using liquid
      chromatography tandem mass spectrometry. Rapid and sustained, statistically
      significant (P <= 0.01) increases in the levels of excretion of the glutathione
      derived conjugates of benzene (61%), acrolein (23%), but not crotonaldehyde, were
      found in those receiving broccoli sprout beverage compared with placebo.
      Excretion of the benzene-derived mercapturic acid was higher in participants who
      were GSTT1-positive than in the null genotype, irrespective of study arm
      assignment. Measures of sulforaphane metabolites in urine indicated that
      bioavailability did not decline over the 12-week daily dosing period. Thus,
      intervention with broccoli sprouts enhances the detoxication of some airborne
      pollutants and may provide a frugal means to attenuate their associated long-term
      health risks.

PMID- 24913820
TI  - Sexual health in oral oncology: breaking the news to patients with human
      papillomavirus-positive oropharyngeal cancer.
AB  - The incidence of oropharyngeal carcinoma is increasing in many countries of the
      developed world, largely because of cancers caused by infection with human
      papillomavirus (HPV). HPV-positive patients may ask questions that fall outside
      the remit of traditional consultations held in head and neck clinics. The purpose
      of this article is to highlight key messages about HPV and oropharyngeal cancer
      that are relevant to patients. Key messages include: HPV is a very common virus
      that transiently infects most people at some point in their lives; HPV infection
      is transmitted by normal sexual activity and is not a marker of promiscuity or
      abnormal sexual practices; HPV infections may be acquired many years before a
      cancer develops and infection does not imply recent infidelity; long-term
      partners of HPV-positive patients do not seem to be at increased risk of HPV
      infection.

PMID- 24913821
TI  - Prevention of nonimmunologic loss of transplanted islets in monkeys.
AB  - The nonimmunologic loss of islets in the pre-, peri-, and early post-islet
      transplant periods is profound. To determine the potential role that
      transplantation of only a marginal mass of functioning beta cells may play in
      triggering late nonimmunologic graft loss, we studied the effect of treatment
      with alpha-1-antitrypsin (AAT) in the autologous cynomolgus islet transplant
      model. A marginal mass of autologous islets, that is islets prepared from 70% to
      80% of the pancreas, was transplanted at 1600-4100 IEQ/kg into subtotal
      pancreatectomized, streptozotocin-treated and insulin-deficient diabetic hosts.
      In this marginal mass islet transplant model, islet function is insidiously lost
      over time and diabetes recurs in all untreated monkeys by 180 days
      posttransplantation. Short-term treatment with AAT, an acute phase reactant, in
      the peri-transplant period serves to terminate inflammation through effects upon
      expression of TGFbeta, NFkappaB and AKT and favorably altering expression of cell
      death and survival pathways, as detected by a system biology approach and
      histology. These effects enabled functional expansion of the islet mass in
      transplanted hosts such that graft function improves rather than deteriorating
      over time. 

PMID- 24913822
TI  - Use of singular value decomposition analysis to differentiate phosphorylated
      precursors in strong cation exchange fractions.
AB  - We studied the use of peak deviations (PDs) for application in phosphoproteomics.
      Due to the differences in the mass defects, the PDs of samples containing
      mixtures of phosphorylated and nonphosphorylated peptides show bimodal
      distributions. The ratios of peak heights accurately predict the phosphoproteome
      content of a sample. In this work, we apply a signal-processing tool, singular
      value decomposition, to reveal characteristic features of the phosphorylated,
      nonphosphorylated, and mixed samples. We show that a simple application of
      singular value decomposition to the PD matrix (i) detects transitions from mostly
      phosphorylated samples to mostly nonphosphorylated samples, (ii) reveals modes of
      low-abundance species in the presence of the high-abundance species (e.g.,
      phosphorylated peptides), and (iii) simplifies the interpretation of the
      clustering of a covariance matrix obtained from PDs. As the eigenfunctions of the
      inner-product of the data matrix (made from the PDs) are Hermite functions, we
      observe a change of sign in the transition from samples enriched in
      phosphorylated peptides to samples containing fewer phosphorylated peptides. The
      ordering of the singular values of the data matrix points in the direction of
      changes to the phosphorylation content. No peptide identifications from a
      database were used for this study. 

PMID- 24913823
TI  - Chitosan-mediated formation of biomimetic silica nanoparticles: an effective
      method for manganese peroxidase immobilization and stabilization.
AB  - Our work here, for the first time, reported the use of chitosan-mediated
      biomimetic silica nanoparticles in enzyme immobilization. In order to make clear
      the relationship among silicification process, silica nanoparticle structure and
      immobilized enzyme activity, a mechanism of chitosan-mediated silicification
      using sodium silicate as the silica source was primarily evaluated. Chitosan was
      demonstrated effectively to promote the silicification not only in accelerating
      the aggregation rate of sodium silicate, but also in templating the formation of
      silica nanoparticles. Although the whole biomimetic silicification process
      contained polycondensation-aggregation-precipitation three stages, the elemental
      unit in precipitated silica was confirmed to be nanoparticles with 100 nm
      diameter regardless of the chitosan and silicate concentration used. Furthermore,
      the effect of enzyme on silicification process was also investigated. The
      introducing of manganese peroxidase (MnP) to silica precursor solution had no
      obvious effect on the silicification rate and nanoparticle morphology. The
      residual activity and embedding rate of immobilized MnP were 64.2% and 36.4%
      respectively under the optimum conditions. In addition, compared to native MnP,
      the MnP embedded in chitosan/silica nanoparticles exhibited improved stability
      against organic solvent and ultrasonic wave. After ultrasonic treatment for 20
      min, 77% of the initial activity was remained due to the protective effect of
      chitosan/silica nanoparticles, while native MnP lost almost all of its original
      activity. 

PMID- 24913824
TI  - CdSe/ZnS quantum dot thin film formation by an electrospray deposition process
      for light-emitting devices.
AB  - About 30 nm quantum-dot thin films are formed by electrospray deposition (ESD)
      process and quantum-dot-light-emitting-diodes (QD-LEDs) are demonstrated. Maximum
      brightness of 23 000 cd m(-2) and current efficiency of 5.9 cd A(-1) are achieved
      with the ESD process. The ESD process can be a potential solution for large area
      quantum dot layers with simple and flexible control. 

PMID- 24913825
TI  - Doping control analysis of trimetazidine and characterization of major
      metabolites using mass spectrometric approaches.
AB  - Since January 2014, the anti-anginal drug trimetazidine [1-(2,3,4
      trimethoxybenzyl)-piperazine] has been classified as prohibited substance by the
      World Anti-Doping Agency (WADA), necessitating specific and robust detection
      methods in sports drug testing laboratories. In the present study, the
      implementation of the intact therapeutic agent into two different initial testing
      procedures based on gas chromatography-mass spectrometry (GC-MS) and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) is reported, along with the
      characterization of urinary metabolites by electrospray ionization-high
      resolution/high accuracy (tandem) mass spectrometry. For GC-MS analyses, urine
      samples were subjected to liquid-liquid extraction sample preparation, while LC
      MS/MS analyses were conducted by established 'dilute-and-inject' approaches. Both
      screening methods were validated for trimetazidine concerning specificity, limits
      of detection (0.5-50 ng/mL), intra-day and inter-day imprecision (<20%), and
      recovery (41%) in case of the GC-MS-based method. In addition, major metabolites
      such as the desmethylated trimetazidine and the corresponding sulfoconjugate, oxo
      trimetazidine, and trimetazidine-N-oxide as identified in doping control samples
      were used to complement the LC-MS/MS-based assay, although intact trimetazidine
      was found at highest abundance of the relevant trimetazidine-related analytes in
      all tested sports drug testing samples. Retrospective data mining regarding
      doping control analyses conducted between 1999 and 2013 at the Cologne Doping
      Control Laboratory concerning trimetazidine revealed a considerable prevalence of
      the drug particularly in endurance and strength sports accounting for up to 39
      findings per year.

PMID- 24913826
TI  - RHINASTHMA-Adolescents: a new quality of life tool for patients with respiratory
      allergy.
AB  - BACKGROUND: Specific instruments for health-related quality of life (HRQoL)
      assessment in adolescents with rhinoconjunctivitis or asthma are available. None
      of them evaluates rhinitis and asthma together, although they often coexist. Our
      aim was to validate a HRQoL questionnaire for adolescents with
      rhinoconjunctivitis, asthma, or both. METHODS: A pool of 38 items covering the
      main symptoms and problems related to respiratory allergy was generated based on
      literature review, clinical experience, and unstructured interviews to 54
      adolescents. The items were randomly listed and presented to 88 consecutive
      outpatients (44 M; mean age 15.2 +/- 3.1). Patients had to indicate which item
      they had experienced and, for each selected item, its importance on a four-point
      scale (1 = not at all; 4 = very much). Twelve items were excluded from the list,
      because of low importance. In the validation phase, 102 patients (54 M; mean age
      15.36 +/- 1.12) completed the KINDL, a generic HRQoL tool, and the new
      questionnaire (RHINASTHMA-Adolescents). RESULTS: Factor analysis revealed a five
      dimensional structure, which explained up to 71.23% of the total variance.
      Association between RHINASTHMA-Adolescents and KINDL scores was all in the
      expected direction. Internal consistency for the extracted factors was
      satisfactory: Upper Airways (0.81), Lower Airways (0.89), Emotions (0.85), Social
      Relationship (0.79), Daily life management (0.74). Reliability was good for all
      factors with a Pearson coefficient ranged from 0.91 to 0.99. CONCLUSIONS:
      RHINASTHMA-Adolescents is the first tool for evaluating HRQoL in patients with
      rhinitis and/or asthma. It provides a simple assessment and met the standards of
      validity, internal consistency, and reliability.

PMID- 24913827
TI  - Delineation of plant caleosin residues critical for functional divergence,
      positive selection and coevolution.
AB  - BACKGROUND: The caleosin genes encode proteins with a single conserved EF hand
      calcium-binding domain and comprise small gene families found in a wide range of
      plant species. These proteins may be involved in many cellular and biological
      processes coupled closely to the synthesis, degradation, or stability of oil
      bodies. Although previous studies of this protein family have been reported for
      Arabidopsis and other species, understanding of the evolution of the caleosin
      gene family in plants remains inadequate. RESULTS: In this study, comparative
      genomic analysis was performed to investigate the phylogenetic relationships,
      evolutionary history, functional divergence, positive selection, and coevolution
      of caleosins. First, 84 caleosin genes were identified from five main lineages
      that included 15 species. Phylogenetic analysis placed these caleosins into five
      distinct subfamilies (sub I-V), including two subfamilies that have not been
      previously identified. Among these subfamilies, sub II coincided with the
      distinct P-caleosin isoform recently identified in the pollen oil bodies of lily;
      caleosin genes from the same lineage tended to be clustered together in the
      phylogenetic tree. A special motif was determined to be related with the
      classification of caleosins, which may have resulted from a deletion in sub I and
      sub III occurring after the evolutionary divergence of monocot and dicot species.
      Additionally, several segmentally and tandem-duplicated gene pairs were
      identified from seven species, and further analysis revealed that caleosins of
      different species did not share a common expansion model. The ages of each pair
      of duplications were calculated, and most were consistent with the time of genome
      wide duplication events in each species. Functional divergence analysis showed
      that changes in functional constraints have occurred between subfamilies I/IV,
      II/IV, and II/V, and some critical amino acid sites were identified during the
      functional divergence. Additional analyses revealed that caleosins were under
      positive selection during evolution, and seven candidate amino acid sites (70R,
      74G, 88 L, 89G, 100 K, 106A, 107S) for positive selection were identified.
      Interestingly, the critical amino acid residues of functional divergence and
      positive selection were mainly located in C-terminal domain. Finally, three
      groups of coevolved amino acid sites were identified. Among these coevolved
      sites, seven from group 2 were located in the Ca2+-binding region of crucial
      importance. CONCLUSION: In this study, the evolutionary and expansion patterns of
      the caleosin gene family were predicted, and a series of amino acid sites
      relevant to their functional divergence, adaptive evolution, and coevolution were
      identified. These findings provide data to facilitate further functional analysis
      of caleosin gene families in the plant lineage.

PMID- 24913828
TI  - Emerging roles for hnRNPs in post-transcriptional regulation: what can we learn
      from flies?
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a highly conserved family
      of RNA-binding proteins able to associate with nascent RNAs in order to support
      their localization, maturation and translation. Research over this last decade
      has remarked the importance of gene regulatory processes at post-transcriptional
      level, highlighting the emerging roles of hnRNPs in several essential biological
      events. Indeed, hnRNPs are key factors in regulating gene expression, thus,
      having a number of roles in many biological pathways. Moreover, failure of the
      activities catalysed by hnRNPs affects various biological processes and may
      underlie several human diseases including cancer, diabetes and neurodegenerative
      syndromes. In this review, we summarize some of hnRNPs' roles in the model
      organism Drosophila melanogaster, particularly focusing on their participation in
      all aspects of post-transcriptional regulation as well as their conserved role
      and involvement in the aetiology of human pathologies.

PMID- 24913830
TI  - Recent HIV infection complicated with leukocytoclastic vasculitis and
      oligoarthritis.

PMID- 24913829
TI  - Androgen receptor (AR) suppresses normal human prostate epithelial cell
      proliferation via AR/beta-catenin/TCF-4 complex inhibition of c-MYC
      transcription.
AB  - INTRODUCTION: Physiologic testosterone continuously stimulates prostate stromal
      cell secretion of paracrine growth factors (PGFs), which if unopposed would
      induce hyperplastic overgrowth of normal prostate epithelial cells (PrECs).
      METHODS: Lentiviral shRNA stable knock down of c-MYC, beta-catenin, or TCF-4
      completely inhibits normal (i.e., non-transformed) human PrECs growth. c-MYC
      enhancer driven reporter expression and growth is inhibited by two chemically
      distinct molecules, which prevent beta-catenin signaling either by blocking TCF-4
      binding (i.e., toxoflavin) or by stimulating degradation (i.e., AVX939).
      Recombinant DKK1 protein at a dose, which inhibits activation of canonical Wnt
      signaling does not inhibit PrEC growth. Nuclear beta-catenin translocation and
      PrEC growth is prevented by both lack of PGFs or Akt inhibitor-I. Growth
      inhibition induced by lack of PGFs, toxoflavin, or Akt inhibitor-I is overcome by
      constitutive c-MYC transcription. RESULTS: In the presence of continuous PGF
      signaling, PrEC hyperplasia is prevented by androgen binding to AR suppressing c
      MYC transcription, resulting in G0 arrest/terminal differentiation independent of
      Rb, p21, p27, FoxP3, or down regulation of growth factors receptors and instead
      involves androgen-induced formation of AR/beta-catenin/TCF-4 complexes, which
      suppress c-MYC transcription. Such suppression does not occur when AR is mutated
      in its zinc-finger binding domain. DISCUSSION: Proliferation of non-transformed
      human PrECs is dependent upon c-MYC transcription via formation/binding of beta
      catenin/TCF-4 complexes at both 5' and 3' c-MYC enhancers stimulated by Wnt
      independent, PGF induced Akt signaling. In the presence of continuous PGF
      signaling, PrEC hyperplasia is prevented by androgen-induced formation of AR/beta
      catenin/TCF-4 complexes, which retains binding to 3' c-MYC enhancer, but now
      suppresses c-MYC transcription.

PMID- 24913831
TI  - Thyroglobulin antibodies and risk of readmission at one year in subjects with
      bipolar disorder.
AB  - Thyroid autoimmunity has been proposed as an endophenotype for Bipolar Disorder
      (BD), although its relationship with clinical outcomes remains unclear. We aimed
      to determine whether thyroid autoimmune status (thyroperoxidase antibodies [TPO
      Abs] and thyroglobulin antibodies [TG-Abs]) in BD is associated with a greater
      risk for readmission at one year. We studied 77 inpatients with BD admitted for
      an index manic or mixed episode. Serum thyroid antibodies (TPO-Abs and TG-Abs)
      were determined at admission. We compared the readmission risk at 1 year, based
      on patients' thyroid autoimmunity profile using survival analyses. Cox regression
      was used to control covariates. TG-Abs+ but not TPO-Abs+ was associated with a
      lower risk of relapse. The Kaplan-Meier mean estimated survival times were 341.6
      days (CI95% 316.4-366.8) for the TG-Abs+ group and 261.9 days (CI95%: 221.8 to
      302.0) for the TG-Abs- group. Cox proportional hazards regression indicated that
      subjects with TG-Abs+ were 3.7 (1/OR=1/0.27) times less likely to get admitted
      during the follow-up period than those with TG-Abs-. Our study suggests that an
      autoimmune biomarker in patients with BD (i.e., the presence of TG-Abs) is
      associated with a lower risk of psychiatric readmission after an index
      hospitalization for a manic or mixed episode. 

PMID- 24913832
TI  - Aspirin for prevention of cardiovascular events in bipolar disorders.

PMID- 24913833
TI  - Paternal age of schizophrenia probands and endophenotypic differences from
      unaffected siblings.
AB  - We evaluated the discrepancy of endophenotypic performance between probands with
      schizophrenia and unaffected siblings by paternal age at proband birth, a
      possible marker for de novo mutations. Pairs of schizophrenia probands and
      unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or
      neurophysiological endophenotypes previously identified as heritable. For each
      endophenotype, the sibling-minus-proband differences were transformed to
      standardized scores. Then for each pair, the average discrepancy was calculated
      from its standardized scores. We tested the hypothesis that the discrepancy is
      associated with paternal age, controlling for the number of endophenotypes shared
      between proband and his or her sibling, and proband age, which were both
      associated with paternal age. The non-significant association between the
      discrepancy and paternal age was in the opposite direction from the hypothesis.
      Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the
      opposite direction. Eight other endophenotypes were also in the opposite
      direction, but not significant. The results did not support the hypothesized
      association of increased differences between sibling/proband pairs with greater
      paternal age. A possible explanation is that the identification of heritable
      endophenotypes was based on samples for which schizophrenia was attributable to
      inherited rather than de novo/non-inherited causes. 

PMID- 24913834
TI  - Protective effects of salidroside in the MPTP/MPP(+)-induced model of Parkinson's
      disease through ROS-NO-related mitochondrion pathway.
AB  - Parkinson's disease is a progressive neurodegenerative disease causing tremor,
      rigidity, bradykinesia, and gait impairment. Oxidative stress and mitochondrial
      dysfunction play important roles in the development of Parkinson disease.
      Salidroside (Sal), a phenylpropanoid glycoside isolated from Rhodiola rosea L.,
      has potent antioxidant properties. Previous work from our group suggests that Sal
      might protect dopaminergic neurons through inhibition of reactive oxygen species
      (ROS) and nitric oxide (NO) generation. In the present study, we investigated the
      protective effects of Sal in MPTP/MPP(+) models of Parkinson's disease in an
      attempt to elucidate the underlying mechanism of protection. We found that Sal
      pretreatment protected dopaminergic neurons against MPTP/MPP(+)-induced toxicity
      in a dose-dependent manner by: (1) reducing the production of ROS-NO, (2)
      regulating the ratio of Bcl-2/Bax, (3) decreasing cytochrome-c and Smac release,
      and inhibiting caspase-3, caspas-6, and caspas-9 activation, and (4) reducing
      alpha-synuclein aggregation. The present study supports the hypothesis that Sal
      may act as an effective neuroprotective agent through modulation of the ROS-NO
      related mitochondrial pathway in vitro and in vivo.

PMID- 24913836
TI  - Immune tolerance in liver disease.
AB  - Liver tolerance is manifest as a bias toward immune unresponsiveness, both in the
      context of a major histocompatibility complex-mismatched liver transplant and in
      the context of liver infection. Two broad classes of mechanisms account for liver
      tolerance. The presentation of antigens by different liver cell types results in
      incomplete activation of CD8(+) T cells, usually leading to initial proliferation
      followed by either clonal exhaustion or premature death of the T cell. Many liver
      infections result in relatively poor CD4(+) T-cell activation, which may be
      because liver antigen-presenting cells express a variety of inhibitory cytokines
      and coinhibitor ligands. Poor CD4(+) T-cell activation by liver antigens likely
      contributes to abortive activation, exhaustion, and early death of CD8(+) T
      cells. In addition, a network of active immunosuppressive pathways in the liver
      is mediated mostly by myeloid cells. Kupffer cells, myeloid-derived suppressor
      cells, and liver dendritic cells both promote activation of regulatory T cells
      and suppress CD8(+) and CD4(+) effector T cells. This suppressive network
      responds to diverse inputs, including signals from hepatocytes, sinusoidal
      endothelial cells, and hepatic stellate cells. CONCLUSION: Though liver tolerance
      may be exploited by pathogens, it serves a valuable purpose. Hepatitis A and B
      infections occasionally elicit a powerful immune response sufficient to cause
      fatal massive liver necrosis. More commonly, the mechanisms of liver tolerance
      limit the magnitude of intrahepatic immune responses, allowing the liver to
      recover. The cost of this adaptive mechanism may be incomplete pathogen
      eradication, leading to chronic infection.

PMID- 24913837
TI  - Training effects of the effortful swallow under three exercise conditions.
AB  - The effortful swallow achieves overload through high effort. It was predicted
      that both immediate effects on biomechanics and long-term neuromuscular
      adaptations would be facilitated by maximal overload during this exercise. This
      study examined how high-effort sips from small-diameter straws influenced
      linguapalatal swallow pressures. Additionally, training effects of effortful
      swallows preceded by high-effort sips were compared to two other exercise
      conditions: effortful swallows preceded by maximum effort lingual elevation and
      effortful swallows performed in isolation. Training outcomes included
      linguapalatal pressures produced during effortful and noneffortful swallows, and
      maximum isometric pressure (MIP) produced during tongue elevation and interlabial
      compression. Forty healthy adults participated in the experiment. Lingual-palatal
      swallowing pressure during non effortful and effortful swallows and MIPs were
      measured prior to and after 4 weeks of training. Prior to training, anterior
      linguapalatal pressures were significantly higher during effortful compared to
      noneffortful swallows. Anterior linguapalatal pressures did not significantly
      differ during swallows preceded by sips from high-resistance straws. Weak
      correlations were observed between tongue MIP and linguapalatal pressures during
      effortful swallows. After training, anterior linguapalatal pressures
      significantly increased, with training effects more dramatic for effortful
      swallows. Anterior tongue MIP also significantly increased. Gains in anterior
      linguapalatal pressure were not correlated with gains in tongue MIP. Training
      effects did not vary across exercise condition. The study failed to find a
      training advantage of pairing the effortful swallow with a precursor movement.
      The results demonstrated specificity of training, with more dramatic benefits
      observed for effortful swallows relative to noneffortful swallows. Further
      investigation is needed to characterize training effects in older adults and
      patients with dysphagia. 

PMID- 24913838
TI  - Beneficial effects of human milk oligosaccharides on gut microbiota.
AB  - Human milk is the gold standard for nourishment of early infants because it
      contains a number of bioactive components, such as human milk oligosaccharides
      (HMOs). The high concentration and structural diversity of HMOs are unique to
      humans. HMOs are a group of complex and diverse glycans that are resistant to
      gastrointestinal digestion and reach the infant colon as the first prebiotics. N
      acetyl-glucosamine containing oligosaccharides were first identified 50 years ago
      as the 'bifidus factor', a selective growth substrate for intestinal
      bifidobacteria, thus providing a conceptual basis for HMO-specific bifidogenic
      activity. Bifidobacterial species are the main utilisers of HMOs in the
      gastrointestinal tract and represent the dominant microbiota of breast-fed
      infants, and they may play an important role in maintaining the general health of
      newborn children. Oligosaccharides are also known to directly interact with the
      surface of pathogenic bacteria, and various oligosaccharides in milk are believed
      to inhibit the binding of pathogens and toxins to host cell receptors.
      Furthermore, HMOs are thought to contribute to the development of infant
      intestine and brain. Oligosaccharides currently added to infant formula are
      structurally different from the oligosaccharides naturally occurring in human
      milk and, therefore, they are unlikely to mimic some of the structure-specific
      effects. In this review, we describe how HMOs can modulate gut microbiota. This
      article summarises information up to date about the relationship between the
      intestinal microbiota and HMOs, and other possible indirect effects of HMOs on
      intestinal environment. 

PMID- 24913839
TI  - Differential effects of lactobacilli on activation and maturation of mouse
      dendritic cells.
AB  - Lactic acid bacteria (LAB) are of interest because of their potential to modulate
      immune responses. The effects of LAB range from regulation to stimulation of the
      immune system. A series of studies were performed in vitro to study the effects
      of six lactic acid bacteria (LAB), Lactobacillus helveticus LH-2, Lactobacillus
      acidophilus La-5, La-115, La-116 and La-14, and Lactobacillus salivarius, on
      maturation and activation of mouse dendritic cells. Production of tumour necrosis
      factor (TNF)-?, interleukin (IL)-6 and IL-10 by dendritic cells (DCs) was
      determined after treating cells with live LAB. The expression of DC maturation
      markers, CD80 and CD40, was also measured using flow cytometry after stimulation
      with LAB. In addition, the expression of Toll-like receptors (TLRs) 2, 4 and 9 by
      DCs stimulated with LAB was measured. Our results revealed that LAB act
      differentially on pro-inflammatory and anti-inflammatory cytokine production and
      induction of co-stimulatory molecules by DCs. Specifically, L. salivarius was
      found to be the most effective LAB to induce pro-inflammatory cytokine production
      and expression of co-stimulatory molecules. Moreover, La-14, La-116 and La-5
      induced moderate maturation and activation of DCs. On the other hand, LH-2 and La
      115 were the least effective lactobacilli to induce DC responses. The present
      study also revealed that L. salivarius was able to induce the expression of TLR2,
      4 and 9 by DCs. In conclusion, various strains and species of LAB can
      differentially regulate DC activation and maturation, providing further evidence
      that these bacteria may have the ability to influence and steer immune responses
      in vivo. 

PMID- 24913842
TI  - Proteases and disease.

PMID- 24913840
TI  - Rhinomonas nottbecki n. sp. (cryptomonadales) and molecular phylogeny of the
      family Pyrenomonadaceae.
AB  - The cryptomonad Rhinomonas nottbecki n. sp., isolated from the Baltic Sea, is
      described from live and fixed cells studied by light, scanning, and transmission
      electron microscopy together with sequences of the partial nucleus- and
      nucleomorph-encoded 18S rRNA genes as well as the nucleus-encoded ITS1, 5.8S,
      ITS2, and the 5'-end of the 28S rRNA gene regions. The sequence analyses include
      comparison with 43 strains from the family Pyrenomonadaceae. Rhinomonas nottbecki
      cells are dorsoventrally flattened, obloid in shape; 10.0-17.2 MUm long, 5.5-8.1
      MUm thick, and 4.4-8.8 MUm wide. The inner periplast has roughly hexagonal
      plates. Rhinomonas nottbecki cells resemble those of Rhinomonas reticulata, but
      the nucleomorph 18S rRNA gene of R. nottbecki differs by 2% from that of R.
      reticulata, while the ITS region by 11%. The intraspecific variability in the ITS
      region of R. nottbecki is 5%. In addition, the predicted ITS2 secondary
      structures are different in R. nottbecki and R. reticulata. The family
      Pyrenomonadaceae includes three clades: Clade A, Clade B, and Clade C. All
      Rhinomonas sequences branched within the Clade C, while the genus Rhodomonas is
      paraphyletic. The analyses suggest that the genus Storeatula is an alternating
      morphotype of the genera Rhinomonas and Rhodomonas and that the family
      Pyrenomonadaceae includes some species that were described multiple times, as
      well as novel species. 

PMID- 24913847
TI  - On the illness of Politian (Agnolo Ambrogini, 1454-1494): syphilis at its
      identification in Europe.
AB  - The authors investigated the life, the works and the illness of the humanist and
      poet Agnolo Ambrogini, better known as Politian, and the cause of his death,
      shedding evidence on the ambiguous meaning of the term scabies that is included
      in the titles of two works ascribed to Politian, namely 'Sylva in scabiem' and
      'De scabie'. These two works tell us the illness that will kill Politian who
      describes them in detail as a new illness that does appear in other important
      works dated between the end of the 15th century and the beginning of the 16th.
      This new illness will be called 'syphilis'. Syphilis was virulent in Europe soon
      after it appeared and it killed Politian within one year. He seems to have been
      the first famous European who was not a physician who described his own syphilis.
      Others include the poet Niccolo Campani (1478-1523), the writer and humanist
      Ulrich Von Hutten (1488-1523), the sculptor and writer Benvenuto Cellini (1500
      1571) and Joseph Grunpeck (1473-1532), and secretary to Emperor Maximilian I
      (1459-1519). The origins of this serious condition have been ascribed to the crew
      who accompanied Christopher Columbus (1451-1506). 

PMID- 24913848
TI  - Johannitius (809-873 AD), a medieval physician, translator and author.
AB  - The medieval physician, translator and author Abu Zayd Hunayn ibn Ishaq al
      'Ibadi, best known in the West as Johannitius, is considered the best translator
      of Greek texts, particularly medical writings, into Arabic. He made great inroads
      in the art of translation in the Islamic world. In addition to his own
      translations, Johannitius put significant effort into training pupils and passing
      knowledge about translation to succeeding generations. He was also a great
      writer, compiling over 100 books on different subjects, especially medical. Among
      his own works, the illustrious Kitab al-Ashr Maqalat fil-Ayn (Ten Treatises on
      the Eye) contains the oldest known illustration of the structure of the eye. It
      served as the primary source for Galen's theory of vision and subsequent use by
      Western scholars. 

PMID- 24913849
TI  - Evaluation of modified Killian's method: a technique to expose the hypopharyngeal
      space.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this study was to evaluate the "Modified
      Killian's method," a recently proposed endoscopic technique to observe a wider
      area of the hypopharngeal space than is possible with the conventional method.
      STUDY DESIGN: Prospective case series. METHODS: Fifty-seven patients underwent
      transnasal flexible endoscopy in a sequence of eight different procedures with or
      without head torsion, the Valsalva maneuver, and a position similar to bowing
      named "the modified Killian position." The visibility of subsites of the
      hypopharynx and esophageal inlet was evaluated based on a 5-point scale. RESULTS:
      The Modified Killian's method, a combination of all three procedures of head
      torsion, the Valsalva maneuver, and the modified Killian position, demonstrated a
      highly significant score for hypopharyngeal visibility. Previous treatment with
      radiotherapy or chemoradiotherapy did not significantly affect the visibility of
      the hypopharynx. CONCLUSION: The newly proposed Modified Killian's method
      provides an effective view of the entire circumference of the hypopharyngeal
      space even in patients receiving radiotherapy. This useful procedure can be
      performed easily and should be a part of flexible laryngoscopy for outpatients.
      LEVEL OF EVIDENCE: 4.

PMID- 24913850
TI  - Hydrophilic-lipophilic balanced magnetic nanoparticles: preparation and
      application in magnetic solid-phase extraction of organochlorine pesticides and
      triazine herbicides in environmental water samples.
AB  - In this study, a novel hydrophilic-lipophilic balanced magnetic nanoparticle,
      magnetic poly(divinylbenzene-co-N-vinylpyrrolidone) (HLB-MPNP) was successfully
      synthesized and applied for the extraction and determination of triazine and
      organochlorine pesticides in environmental water samples. The specific ratio of
      two monomers, hydrophilic N-vinylpyrrolidone and lipophilic divinylbenzene,
      endowed the magnetic nanoparticles with hydrophilic-lipophilic balanced
      character, which made it capable of extracting both polar and nonpolar analytes.
      The experimental parameters affecting extraction efficiency, including desorption
      conditions, sample pH, sample volume and extraction time were investigated and
      optimized. Under the optimum conditions, good linearity was obtained in the range
      of 0.20-10 MUg L(-1) for triazine herbicides and 5.0-100 ng L(-1) for
      organochlorine pesticides, with correlation coefficients ranging from 0.994 to
      0.999. The limits of determination were between 0.048 and 0.081 MUg L(-1) for
      triazine herbicides and 0.39 and 3.26 ng L(-1) for organochlorine pesticides. The
      proposed method was successfully applied in the analysis of triazine and
      organochlorine pesticides in environmental water samples (ground, river and
      reservoir).

PMID- 24913851
TI  - Cholinesterase sensor based on glassy carbon electrode modified with Ag
      nanoparticles decorated with macrocyclic ligands.
AB  - New acetylcholinesterase (AChE) sensor based on Ag nanoparticles decorated with
      macrocyclic ligand has been developed and successfully used for highly sensitive
      detection of organophosphate and carbamate pesticides. AChE was immobilized by
      carbodiimide binding on carbon black (CB) layer deposited on a glassy carbon
      electrode. The addition of Ag nanoparticles decreased the working potential of
      the biosensor from 350 to 50 mV. The AChE sensor made it possible to detect 0.4
      nM-0.2 MUM of malaoxon, 0.2 nM-0.2 MUM of paraoxon, 0.2 nM-2.0 MUM of carbofuran
      and 10 nM-0.20 MUM of aldicarb (limits of detection 0.1, 0.05, 0.1 and 10 nM,
      respectively) with 10 min incubation. The AChE sensor was tested for the
      detection of residual amounts of pesticides in spiked samples of peanut and grape
      juice. The protecting effect of new macrocyclic compounds bearing quaternary
      ammonia fragments was shown on the example of malaoxon inhibition.

PMID- 24913852
TI  - A new extraction approach to correct the effect of apparent increase in the
      secoiridoid content after filtration of virgin olive oil.
AB  - In the current study, a new approach has been developed for correcting the effect
      that moisture reduction after virgin olive oil (VOO) filtration exerts on the
      apparent increase of the secoiridoid content by using an internal standard during
      extraction. Firstly, two main Spanish varieties (Picual and Hojiblanca) were
      submitted to industrial filtration of VOOs. Afterwards, the moisture content was
      determined in unfiltered and filtered VOOs, and liquid-liquid extraction of
      phenolic compounds was performed using different internal standards. The
      resulting extracts were analyzed by HPLC-ESI-TOF/MS, in order to gain maximum
      information concerning the phenolic profiles of the samples under study. The
      reduction effect of filtration on the moisture content, phenolic alcohols, and
      flavones was confirmed at the industrial scale. Oleuropein was chosen as internal
      standard and, for the first time, the apparent increase of secoiridoids in
      filtered VOO was corrected, using a correction coefficient (Cc) calculated from
      the variation of internal standard area in filtered and unfiltered VOO during
      extraction. This approach gave the real concentration of secoiridoids in filtered
      VOO, and clarified the effect of the filtration step on the phenolic fraction.
      This finding is of great importance for future studies that seek to quantify
      phenolic compounds in VOOs. 

PMID- 24913854
TI  - Experimental performances study of a transportable GC-PID and two thermo
      desorption based methods coupled to FID and MS detection to assess BTEX exposure
      at sub-ppb level in air.
AB  - BTEX compounds are of particular interest, above all benzene because it is a
      carcinogenic compound for which guideline value in European indoor environments
      is set to be 1.6 ppb. Therefore, the detection of such relatively low value
      requires the use of particularly sensitive analytical techniques. Several
      existing chromatographic techniques, such as fast and transportable Gas
      Chromatograph with Photoionization Detection (GC-PID) or sedentary
      chromatographic-based techniques equipped with a thermo-desorption device (ATD)
      and coupled to either Flame Ionization Detection (FID) or Mass Spectrometry (MS),
      can quantify benzene and its derivatives at such low levels. These instruments
      involve different injection modes, i.e. on-line gaseous sampling or thermo
      desorption of adsorbent tubes spiked with liquid or gas samples. In this study,
      the performances of 3 various analytical techniques mentioned above were compared
      in terms of sensitivity, linearity, accuracy and repeatability for the 6 BTEX.
      They were also discussed related to their analyses time consumption or
      transportability. The considered analytical techniques are ATD-GC-FID, ATD-GC-MS
      where both full scan and SIM modes were tested and a transportable GC-PID. For
      benzene with on-line injection, Limits of Detection (LOD) were significantly
      below the European guideline with values of 0.085, 0.022, 0.007 and 0.058 ppb for
      ATD-GC-FID, ATD-GC-MS in a full scan mode, ATD-GC-MS in an SIM mode and
      transportable GC-PID, respectively. LOD obtained with adsorbent tubes spiked with
      liquid standards were approximately in the same order of magnitude.

PMID- 24913853
TI  - A highly improved method for sensitive determination of amitriptyline in
      pharmaceutical formulations using an unmodified carbon nanotube electrode in the
      presence of sulfuric acid.
AB  - The present paper describes a novel, simple and reliable differential pulse
      voltammetric method for determining amitriptyline (AMT) in pharmaceutical
      formulations. It has been described for many authors that this antidepressant is
      electrochemically inactive at carbon electrodes. However, the procedure proposed
      herein consisted in electrochemically oxidizing AMT at an unmodified carbon
      nanotube paste electrode in the presence of 0.1 mol L(-1) sulfuric acid used as
      electrolyte. At such concentration, the acid facilitated the AMT electroxidation
      through one-electron transfer at 1.33 V vs. Ag/AgCl, as observed by the
      augmentation of peak current. Concerning optimized conditions (modulation time 5
      ms, scan rate 90 mV s(-1), and pulse amplitude 120 mV) a linear calibration curve
      was constructed in the range of 0.0-30.0 MUmol L(-1), with a correlation
      coefficient of 0.9991 and a limit of detection of 1.61 MUmol L(-1). The procedure
      was successfully validated for intra- and inter-day precision and accuracy.
      Moreover, its feasibility was assessed through analysis of commercial
      pharmaceutical formulations and it has been compared to the UV-vis
      spectrophotometric method used as standard analytical technique recommended by
      the Brazilian Pharmacopoeia.

PMID- 24913855
TI  - In situ tracking the intracellular delivery of antisense oligonucleotides by
      fluorescein doped silica nanoparticles.
AB  - Antisense oligonucleotides (ASOs) are often utilized to interfere with gene
      expression at mRNA level for cancer treatment. Here, we synthesized fluorescein
      doped silica nanoparticles (FSNPs) and coated them by polyethyleneimine (PEI) for
      carrying ASOs. Agarose gel electrophoresis proved that PEI/FSNPs could load ASOs
      by a weight ratio as high as 30:1. We tracked the delivery process of ASOs from
      the ASOs/PEI/FSNPs composites to HeLa cells in situ by the confocal laser
      scanning microscopy (CLSM) techniques, including nuclear staining and Z-axis
      scanning. We found the ASOs/PEI/FSNPs composites exhibited their biological
      effects at specific intracellular localization, and the fluorescence of the FSNPs
      showed the dynamic delivery process in the cells. 

PMID- 24913856
TI  - Salting-out assisted liquid-liquid extraction combined with capillary HPLC for
      the determination of sulfonylurea herbicides in environmental water and banana
      juice samples.
AB  - A salting-out assisted liquid-liquid extraction (SALLE) combined with capillary
      high performance liquid chromatography with diode array detector (capillary HPLC
      DAD) was proposed for extraction and determination of residues of nine
      sulfonylurea herbicides (SUHs) in environmental water and banana juice samples.
      Various parameters affecting the extraction process such as the type and volume
      of the organic solvent, sample volume, type and amount of salt, pH of the sample
      and vortex time were optimized. Under optimum conditions, matrix matched
      calibration curves were established using river water and banana juice samples.
      Good linear relationships as well as low limits of detection, LODs (0.4-1.3 and 3
      13 ug/L) and quantification, LOQs (1.3-4.3 and 10-43 ug/L) were obtained in water
      and banana juice samples, respectively. The precision (intra- and inter-day) of
      the peak areas expressed as relative standard deviations (%, RSD), at two
      concentration levels were below 10 % in both matrices. Recoveries obtained from
      spiked environmental waters (river water and groundwater) and banana juice
      samples, at two concentration levels, ranged from 72 to 115%. The results of the
      analysis revealed that the proposed SALLE-capillary HPLC method is simple, rapid,
      cheap and environmentally friendly, being successfully applicable for the
      determination of SUH residues in waters and banana juices.

PMID- 24913857
TI  - Comparison between solid phase microextraction (SPME) and hollow fiber liquid
      phase microextraction (HFLPME) for determination of extractables from post
      consumer recycled PET into food simulants.
AB  - Hollow fiber liquid phase microextraction (HFLPME) and solid phase
      microextraction (SPME) methods for pre-concentration of contaminants (toluene,
      benzophenone, tetracosane and chloroform) in food simulants were investigated.
      For HFLPME 1-heptanol, 2-octanone and dibutyl-ether were studied as extracting
      solvents. Analysis by gas chromatography coupled to mass spectrometry (GC-MS),
      flame ionization (GC-FID) and electron capture detectors (GC-ECD) were carried
      out. In addition, the methods were employed to evaluate the safety in use of a
      PET material after the recycling process (comprising washing, extrusion and solid
      state polymerization (SSP)) through extractability studies of the contaminants
      using 10% (v/v) ethanol in deionized water and 3% (w/v) acetic acid in deionized
      water as food simulants in different conditions: 10 days at 40 degrees C and 2h
      at 70 degrees C. The HFLPME preconcentration method provided increased
      sensitivity when compared to the SPME method and allowed to analyze concentration
      levels below 10 ug surrogate per kg food simulant. The results of the
      extractability studies showed considerable reductions after the extrusion and SSP
      processes and indicated the compliance with regulations for using recycled PET in
      contact with food.

PMID- 24913858
TI  - Presence of photoluminescent carbon dots in Nescafe(r) original instant coffee:
      applications to bioimaging.
AB  - The presence of the carbon dots (C-dots) in food is a hotly debated topic and our
      knowledge about the presence and the use of carbon dots (C-dots) in food is still
      in its infancy. We report the finding of the presence of photoluminescent (PL) C
      dots in commercial Nescafe instant coffee. TEM analysis reveals that the
      extracted C-dots have an average size of 4.4 nm. They were well-dispersed in
      water and strongly photoluminescent under the excitation of ultra-violet light
      with a quantum yield (QY) about 5.5%, which were also found to possess clear
      upconversion PL properties. X-ray photoelectron spectroscopy characterization
      demonstrates that the C-dots contain C, O and N three elements with the relative
      contents ca. 30.1, 62.2 and 7.8%. The X-ray diffraction (XRD) analysis indicates
      that the C-dots are amorphous. Fourier-transform infrared (FTIR) spectra were
      employed to characterize the surface groups of the C-dots. The C-dots show a pH
      independent behavior by varying the pH value from 2 to 11. The cytotoxicity study
      revealed that the C-dots did not cause any toxicity to cells at a concentration
      as high as 20 mg/mL. The C-dots have been directly applied in cells and fish
      imaging, which suggested that the C-dots present in commercial coffee may have
      more potential biological applications.

PMID- 24913859
TI  - Monitoring of heavy metal particle emission in the exhaust duct of a foundry
      using LIBS.
AB  - Heavy metals have long been known to be detrimental to human health and the
      environment. Their emission is mainly considered to occur via the atmospheric
      route. Most of airborne heavy metals are of anthropogenic origin and produced
      through combustion processes at industrial sites such as incinerators and
      foundries. Current regulations impose threshold limits on heavy metal emissions.
      The reference method currently implemented for quantitative measurements at
      exhaust stacks consists of on-site sampling of heavy metals on filters for the
      particulate phase (the most prominent and only fraction considered in this study)
      prior to subsequent laboratory analysis. Results are therefore known only a few
      days after sampling. Stiffer regulations require the development of adapted tools
      allowing automatic, on-site or even in-situ measurements with temporal
      resolutions. The Laser-Induced Breakdown Spectroscopy (LIBS) technique was deemed
      as a potential candidate to meet these requirements. On site experiments were run
      by melting copper bars and monitoring emission of this element in an exhaust duct
      at a pilot-scale furnace in a French research center dedicated to metal casting.
      Two approaches designated as indirect and direct analysis were broached in these
      experiments. The former corresponds to filter enrichment prior to subsequent LIBS
      interrogation whereas the latter entails laser focusing right through the aerosol
      for detection. On-site calibration curves were built and compared with those
      obtained at laboratory scale in order to investigate possible matrix and analyte
      effects. Eventually, the obtained results in terms of detection limits and
      quantitative temporal monitoring of copper emission clearly emphasize the
      potentialities of the direct LIBS measurements. 

PMID- 24913860
TI  - Lipoxin A4: problems with its determination using reversed phase chromatography
      tandem mass spectrometry and confirmation with chiral chromatography.
AB  - Lipoxins belong to the family of so-called pro-resolving endogenous lipid
      mediators which are derived from arachidonic acid and play a key role in the
      counter-regulation of inflammation. Arachidonic acid is also precursor of
      multiple pro-inflammatory lipid mediators, such as prostaglandins and
      leukotrienes, which are simultaneously present in biological compartments. The
      close structural relationship between several of these lipid mediators and the
      absence of blank matrix samples enormously complicates the unequivocal
      identification of these compounds. The determination of lipoxin A4 has been
      accomplished by chromatographic separation using a C18 reversed phase column and
      tandem mass spectrometry detection. Samples were liquid-liquid extracted with
      ethyl acetate before injection. Identification of the analyte was done based on
      three criteria: retention time, ratio of the m/z transitions and MS/MS spectrum.
      To avoid false positive results due to endogenous interferences, the extracted
      samples were re-injected into a chiral Lux Amylose-2 chromatographic column. The
      authors recommend the use of chiral chromatography in the determination of pro
      resolving lipid mediators, together with transition area ratio and fragmentation
      spectra to improve selectivity for identification and quantitation purposes. 

PMID- 24913861
TI  - Polydopamine-coated eppendorf tubes for Ti4+ immobilization for selective
      enrichment of phosphopeptides.
AB  - Mass spectrometric technique has emerged as a preferred technique in the analysis
      of protein phosphorylation. Owing to the low stoichiometry of phosphopeptides and
      the signal suppression effect by non-phosphopeptides, there is a demand for
      efficient enrichment of phosphopeptides. The selective enrichment of
      phosphopeptides in modified eppendorf tubes prior to mass spectrometry analysis,
      which can minimize sample loss as well as nonspecific interferences effectively,
      has become a hot topic in current proteomics field. In our work, an easy-to-use
      phosphopeptide-selective eppendorf tube was initially prepared, with its inner
      surface being modified with a Ti(4+)-immobilized polydopamine (PDA) layer. The
      unique Ti(4+)-immobilized PDA-modified eppendorf tubes (EP tube@PDA-Ti(4+)) are
      investigated for its application in selective enrichment of phosphopeptides from
      complex biological samples. Due to the high Ti(4+) loading amount on the surface
      of PDA, the EP tube@PDA-Ti(4+) exhibits remarkable phosphopeptide enrichment
      ability in protein digests and human serum, which presents a powerful evidence
      for its high selectivity in detecting the low-abundance phosphopeptides from
      complex biological samples. 

PMID- 24913862
TI  - A new Methimazole sensor based on nanocomposite of CdS NPs-RGO/IL-carbon paste
      electrode using differential FFT continuous linear sweep voltammetry.
AB  - A Methimazole sensor was designed and constructed based on nanocomposite of
      carbon, ionic liquid, reduced graphene oxide (RGO) and CdS nanoparticles. The
      sensor signal was obtained by Differential FFT continuous linear sweep
      voltammetry (DFFTCLSV) technique. The potential waveform contains two sections,
      preconcentration potential and potential ramp. In this detection technique, after
      subtracting the background current from noise, the electrode response was
      calculated, based on partial and total charge exchanges at the electrode surface.
      The combination of RGO and CdS nanoparticles can catalyze the electron transfer,
      which outcomes of the amplification of the sensor signal. The result showed that
      the sensor response was proportional to the concentrations of Methimazole in the
      range of 2.0 to 300 nM, with a detection limit of 5.5*10(-10) M. The sensor
      showed good reproducibility, long-term of usage stability and accuracy. The
      characterization of the sensor surface was studied by atomic force Microscopy and
      Electrochemical Impedance Spectroscopy. Moreover, the proposed sensor exhibited
      good accuracy, and R.S.D value of 2.82%, and the response time of less than 7 s.

PMID- 24913863
TI  - Improved selectivity towards NO2 of phthalocyanine-based chemosensors by means of
      original indigo/nanocarbons hybrid material.
AB  - A new and original gas sensor-system dedicated to the selective monitoring of
      nitrogen dioxide in air and in the presence of ozone, has been successfully
      achieved. Because of its high sensitivity and its partial selectivity towards
      oxidizing pollutants (nitrogen dioxide and ozone), copper phthalocyanine-based
      chemoresistors are relevant. The selectivity towards nitrogen dioxide results
      from the implementation of a high efficient and selective ozone filter upstream
      the sensing device. Thus, a powdered indigo/nanocarbons hybrid material has been
      developed and investigated for such an application. If nanocarbonaceous material
      acts as a highly permeable matrix with a high specific surface area, immobilized
      indigo nanoparticles are involved into an ozonolysis reaction with ozone leading
      to the selective removal of this analytes from air sample. The filtering yields
      towards each gas have been experimentally quantified and establish the complete
      removal of ozone while having the concentration of nitrogen dioxide unchanged.
      Long-term gas exposures reveal the higher durability of hybrid material as
      compared to nanocarbons and indigo separately. Synthesis, characterizations by
      many complementary techniques and tests of hybrid filters are detailed. Results
      on sensor-system including CuPc-based chemoresistors and indigo/carbon nanotubes
      hybrid material as in-line filter are illustrated. Sensing performances will be
      especially discussed. 

PMID- 24913864
TI  - Simultaneous determination of 17 disperse dyes in textile by ultra-high
      performance supercritical fluid chromatography combined with tandem mass
      spectrometry.
AB  - A simple, highly sensitive and fast procedure for the control of 17 allergenic
      and prohibited disperse dyes in textile products was optimized. The method was
      based on ultrasound assisted extraction of textile samples with 10 mL of methanol
      under controlled conditions (30 min, 70 degrees C). The extracts were analyzed by
      the ultra-high performance supercritical fluid chromatography (UHPSFC) system
      coupled with triple quadrupole tandem mass spectrometry (MS/MS). Four stationary
      phases (BEH, BEH 2-ethyl-pyridine, HSS C18 SB and CSH fluorophenyl) were screened
      as well as analytical conditions (modifier percentage, backpressure and column
      temperature) were investigated to improve the separation. All 17 disperse dyes
      were simultaneously separated and determined by UHPSFC-MS/MS in 5 min. The dyes
      were monitored via the ESI(+) ionization method and quantified by 3-channel
      multiple reaction monitoring (MRM). The calibrations were performed and good
      linear relationship (R>=0.99) was observed within the concentration range of 2-50
      MUg mL(-1). Satisfactory recoveries (70.55-103.03%) of all the disperse dyes
      spiked with standards at different levels were demonstrated. This is the first
      report on the simultaneous analysis of disperse dyes using UHPSFC-MS/MS.

PMID- 24913865
TI  - Facile fabrication of a novel anisotropic gold nanoparticle-chitosan-ionic
      liquid/graphene modified electrode for the determination of theophylline and
      caffeine.
AB  - In the present study, a suspension solution containing anisotropic gold
      nanoparticle (GNP), chitosan (CHIT) and ionic liquid (IL, i.e. 1-butyl-3
      methylimidazolium tetrafluoroborate, [BMIM][BF4]), is prepared by reducing HAuCl4
      with sodium citrate in CHIT-IL aqueous solution. The hybrid solution is coated on
      a graphene (r-GO) modified glassy carbon electrode to construct an
      electrochemical sensor for the determination of theophylline (TP) and caffeine
      (CAF). The obtained hybrid film shows rough surface, and anisotropic GNPs are
      well dispersed on it. The factors concerning this assay strategy are carefully
      investigated, including the components of the hybrid film, the concentrations of
      r-GO, HAuCl4 and IL, and the pH of buffer solution. Under the optimized
      conditions, the linear response ranges are 2.50*10(-8)-2.10*10(-6) mol L(-1) and
      2.50*10(-8)-2.49*10(-6) mol L(-1) for TP and CAF, respectively; the detection
      limits are 1.32*10(-9) mol L(-1) and 4.42*10(-9) mol L(-1), respectively. The
      electrochemical sensor shows good reproducibility, stability and selectivity, and
      it has been successfully applied to the determination of TP and CAF in real
      samples.

PMID- 24913866
TI  - Rapid and sensitive liquid chromatography-tandem mass spectrometry method for
      determination of protein-free pro-drug treosulfan and its biologically active
      monoepoxy-transformer in plasma and brain tissue.
AB  - For the first time a high performance liquid chromatography method with tandem
      mass spectrometry detection (HPLC-MS/MS) was developed for simultaneous
      determination of a pro-drug treosulfan (TREO) and its active monoepoxide (S,S
      EBDM) in biological matrices. Small volumes of rat plasma (50 MUL) and the brain
      homogenate supernatant (100 MUL), equivalent to 0.02 g of brain tissue, were
      required for the analysis. Protein-free TREO, S,S-EBDM and acetaminophen,
      internal standard (IS), were isolated from the samples by ultrafiltration.
      Complete resolution of the analytes and the IS was accomplished on Zorbax Eclipse
      column using an isocratic elution with a mobile phase composed of ammonium
      formate - formic acid buffer pH 4.0 and acetonitrile. Detection was performed on
      a triple-quadrupole MS via multiple-reaction-monitoring following electrospray
      ionization. The developed method was fully validated according to the current
      guidelines of the European Medicines Agency. Calibration curves were linear in
      ranges: TREO 0.2-5720 MUM and S,S-EBDM 0.9-175 MUM for plasma, and TREO 0.2-29
      MUM and S,S-EBDM 0.4-44 MUM for the brain homogenate supernatant. The limits of
      quantitation of TREO and S,S-EBDM in the studied matrices were much lower in
      comparison to the previously used bioanalytical methods. The HPLC-MS/MS method
      was adequately precise (coefficient of variation<=12.2%), accurate (relative
      error<=8.6%), and provided no carry-over, acceptable matrix effect as well as
      dilution integrity. The analytes were stable in acidified plasma and the brain
      homogenate supernatant samples for 4 h at room temperature, for 4 months at-80
      degrees C as well as within two cycles of freezing and thawing, and demonstrated
      18-24h autosampler stability. The validated method enabled determination of low
      concentrations of TREO and S,S-EBDM in incurred brain samples of the rats treated
      with TREO, which constitutes a novel bioanalytical application.

PMID- 24913867
TI  - Functionalized anion exchange stationary phase for separation of anionic
      compounds.
AB  - Synthesis of the multilayered stationary phases containing quaternary ammonium
      functional groups on the silica support was described. Bonded phases were
      characterized by elemental analysis, solid state (13)C NMR spectroscopy and
      chromatographic methods. The surface of silica support was coated with different
      number of polymeric layers formed by condensation polymerization of primary amine
      (methylamine) with diepoxide (1,4-butanedioldiglycidyl ether). A series of
      stationary phases with different number of polymerized layers were tested.
      Separation of an inorganic anions sample (F(-), Cl(-), NO2(-), Br(-), NO3(-)) and
      nucleotides was performed. 

PMID- 24913868
TI  - Determination of copper in airborne particulate matter using slurry sampling and
      chemical vapor generation atomic absorption spectrometry.
AB  - The present paper describes the development of a method for the determination of
      copper in airborne particulate matter using slurry sampling and chemical vapor
      generation atomic absorption spectrometry (CVG AAS). Chemometric tools were
      employed to characterize the influence of several factors on the generation of
      volatile copper species. First, a two-level full factorial design was performed
      that included the following chemical variables: hydrochloric acid concentration,
      tetrahydroborate concentration, sulfanilamide concentration and tetrahydroborate
      volume, using absorbance as the response. Under the established experimental
      conditions, the hydrochloric acid concentration had the greatest influence on the
      generation of volatile copper species. Subsequently, a Box-Behnken design was
      performed to determine the optimum conditions for these parameters. A second
      chemometric study employing a two-level full factorial design was performed to
      evaluate the following physical factors: tetrahydroborate flow rate, flame
      composition, alcohol volume and sample volume. The results of this study
      demonstrated that the tetrahydroborate flow rate was critical for the process.
      The chemometric experiments determined the following experimental conditions for
      the method: hydrochloric acid concentration, 0.208 M; tetrahydroborate
      concentration, 4.59%; sulfanilamide concentration, 0.79%; tetrahydroborate
      volume, 2.50 mL; tetrahydroborate flow rate, 6.50 mL min(-1); alcohol volume, 200
      uL; and sample volume, 7.0 mL. Thus, this method, using a slurry volume of 500 uL
      and a final dilution of 7 mL, allowed for the determination of copper with limits
      of detection and quantification of 0.30 and 0.99 ug L(-1), respectively.
      Precisions, expressed as RSD%, of 4.6 and 2.8% were obtained using copper
      solutions at concentrations of 5.0 and 50.0 ug L(-1), respectively. The accuracy
      was evaluated by the analysis of a certified reference material of urban
      particulate matter. The copper concentration obtained was 570+/-63 mg kg(-1), and
      the certified value was 610+/-70 mg kg(-1). This method was applied for the
      determination of copper in airborne particulate matter samples collected in two
      Brazilian regions of Bahia State, Brazil. The copper contents found varied from
      14.46 to 164.31 ng m(-3).

PMID- 24913869
TI  - Evaluation of the plasticization of ion-selective electrode membranes by pulsed
      NMR analyses.
AB  - The potentiometric polymeric membranes for ion-selective electrodes were
      evaluated by analyses of the proton spin-spin relaxation times T2 with pulsed
      NMR. The T2 measurements were performed using the Hahn-Echo, Solid-Echo and CPMG
      pulse sequences. The T2 values and fractions F of each component were obtained by
      analyses of the FID signals measured with the Hahn-Echo pulse sequence. The
      softer potentiometric polymeric membrane possessed the main fraction F(L),
      providing a relatively longer T(2L) value. A linear relationship existed between
      the weight ratio of the membrane solvent and ln T(2L) (or ln total T2*F). This
      analysis method could quantify the degree of hardness or softness of the
      potentiometric polymeric membranes with the differences in the membrane solvent
      weight. The normalized derivative spectra were acquired from the transverse
      magnetization M(t) data measured by using the Solid-Echo and CPMG pulse
      sequences. In the normalized derivative spectra of the potentiometric polymeric
      membranes, most PVC peaks in the short time region shifted to a larger area of
      long time regions by plasticization, and the softer potentiometric polymeric
      membrane incorporating more membrane solvent exhibited a relaxation peak in the
      relatively longer time region. Thus, the normalized derivative spectra were
      effective in elucidating the compatibility of the PVC with the membrane solvent.

PMID- 24913870
TI  - Characterization of TATP gas phase product ion chemistry via isotope labeling
      experiments using ion mobility spectrometry interfaced with a triple quadrupole
      mass spectrometer.
AB  - Identification of the fragment ion species associated with the ion reaction
      mechanism of triacetone triperoxide (TATP), a homemade peroxide-based explosive,
      is presented. Ion mobility spectrometry (IMS) has proven to be a key analytical
      technique in the detection of trace explosive material. Unfortunately, IMS alone
      does not provide chemical identification of the ions detected; therefore, it is
      unknown what ion species are actually formed and separated by the IMS. In IMS,
      ions are primarily characterized by their drift time, which is dependent on the
      ion's mass and molecular cross-section; thus, IMS as a standalone technique does
      not provide structural signatures, which is in sharp contrast to the chemical and
      molecular information that is generally obtained from other customary analytical
      techniques, such as NMR, Raman and IR spectroscopy and mass spectrometry. To help
      study the ion chemistry that gives rise to the peaks observed in IMS, the
      hardware of two different commercial IMS instruments has been directly coupled to
      triple quadrupole (QQQ) mass spectrometers, in order to ascertain each ion's
      corresponding mass/charge (m/z) ratios with different dopants at two
      temperatures. Isotope labeling was then used to help identify and confirm the
      molecular identity of the explosive fragment and adduct ions of TATP. The m/z
      values and isotope labeling experiments were used to help propose probable
      molecular formulas for the ion fragments. In this report, the fragment and adduct
      ions m/z 58 and 240 of TATP have been confirmed to be [C3H6NH.H](+) and
      [TATP.NH4](+), respectively; while the fragment ions m/z 73 and 89 of TATP are
      identified as having the molecular formulas [C4H9NH2](+) and [C4H9O2](+),
      respectively. It is anticipated that the work in this area will not only help to
      facilitate improvements in mobility-based detection (IMS and MS), but also aid in
      the development and optimization of MS-based detection algorithms for TATP.

PMID- 24913871
TI  - A sensitive gold nanoparticle-based colorimetric aptasensor for Staphylococcus
      aureus.
AB  - In this study, a gold nanoparticle-based colorimetric aptasensor for
      Staphylococcus aureus (S. aureus) using tyramine signal amplification (TSA)
      technology has been developed. First, the biotinylated aptamer specific for S.
      aureus was immobilized on the surface of the wells of the microtiter plate via
      biotin-avidin binding. Then, the target bacteria (S. aureus), biotinylated
      aptamer-streptavidin-HRP conjugates, biotinylated tyramine, hydrogen peroxide and
      avidin-catalase were successively introduced into the wells of the microtiter
      plate. After that, the existing catalase consumed the hydrogen peroxide. Finally,
      the freshly prepared gold (III) chloride trihydrate was added, the color of the
      reaction production would be changed and the absorbance at 550 nm could be
      measured with a plate reader. Under optimized conditions, there was a linear
      relationship between the absorbance at 550 nm and the concentration of S. aureus
      over the range from 10 to 10(6) cfu mL(-1) (with an R2 of 0.9947). The limit of
      the developed method was determined to be 9 cfu mL(-1).

PMID- 24913872
TI  - A derivative photoelectrochemical sensing platform for herbicide acetochlor based
      on TiO2-poly (3-hexylthiophene)-ionic liquid nanocomposite film modified
      electrodes.
AB  - Nonelectroactive acetochlor can be indirectly determined through the
      photocatalytical degradation of acetochlor. A derivative visible light
      photoelectrochemical sensor for indirect detection of the herbicide acetochlor
      using TiO2-poly(3-hexylthiophene)-ionic liquid nanocomposite is constructed.
      Poly(3-hexylthiophene) (P3HT) was synthesized via chemical oxidative
      polymerization with anhydrous FeCl3 as oxidant, 3-hexylthiophene as monomer,
      chloroform as solvent, and the functional TiO2 nanoparticles were facilely
      prepared by blending TiO2 nanoparticles and P3HT at room temperature ionic
      liquid, 1-Butyl-3-methylimidazolium hexafluorophosphate solution. Operational
      parameters, including the photolysis time, ratios of TiO2 to P3HT, bias voltage
      and pH of buffer solution have been optimized. Under optimal conditions, the
      proposed photoelectrochemical method could detect acetochlor ranging from 0.5 to
      20 MUmol L(-1) with a detection limit of 0.2 nmol L(-1) at a signal-to-noise
      ratio of 3. The assay results of acetochlor in water samples with the proposed
      method were in acceptable agreement with those of the gas chromatograph-mass
      spectrometer (GC-MS) method. The promising sensor opens a new opportunity for
      fast, portable, and sensitive analysis of acetochlor in environmental samples.

PMID- 24913873
TI  - Speciation of iodine-containing proteins in Nori seaweed by gel electrophoresis
      laser ablation ICP-MS.
AB  - An analytical approach providing an insight into speciation of iodine in water
      insoluble fraction of edible seaweed (Nori) was developed. The seaweed, harvested
      in the Galician coast (Northwestern Spain), contained 67.7+/-1.3 MUg g(-1) iodine
      of which 25% was water soluble and could be identifies as iodide. Extraction
      conditions of water insoluble residue using urea, NaOH, SDS and Triton X-100 were
      investigated. The protein pellets obtained in optimized conditions (after
      precipitation of urea extracts with acetone), were digested with trypsin and
      protease XIV. Size exclusion chromatography-ICP-MS of both enzymatic digests
      demonstrated the occurrence of iodoaminoacids putatively present in proteins.
      Intact proteins could be separated by gel electrophoresis after an additional
      extraction of the protein extract with phenol. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS PAGE) with laser ablation ICP-MS
      detection of (127)I indicated the presence of iodine in protein bands
      corresponding to molecular masses of 110 kDa, 40 kDa, 27 kDa, 20 kDa and 10 kDa.
      2D IEF-SDS PAGE with laser ablation ICP-MS (127)I imaging allowed the detection
      of 5 iodine containing protein spots in the alkaline pI range.

PMID- 24913874
TI  - Infrared biospectroscopy for a fast qualitative evaluation of sample preparation
      in metabolomics.
AB  - Liquid chromatography-mass spectrometry (LC-MS) has been increasingly used in
      biomedicine to study the dynamic metabolomic responses of biological systems
      under different physiological or pathological conditions. To obtain an integrated
      snapshot of the system, metabolomic methods in biomedicine typically analyze
      biofluids (e.g. plasma) that require clean-up before being injected into LC-MS
      systems. However, high resolution LC-MS is costly in terms of resources required
      for sample and data analysis and care must be taken to prevent chemical (e.g. ion
      suppression) or statistical artifacts. Because of that, the effect of sample
      preparation on the metabolomic profile during metabolomic method development is
      often overlooked. This work combines an Attenuated Total Reflectance-Fourier
      transform infrared (ATR-FTIR) and a multivariate exploratory data analysis for a
      cost-effective qualitative evaluation of major changes in sample composition
      during sample preparation. ATR-FTIR and LC-time of flight mass spectrometry
      (TOFMS) data from the analysis of a set of plasma samples precipitated using
      acetonitrile, methanol and acetone performed in parallel were used as a model
      example. Biochemical information obtained from the analysis of the ATR-FTIR and
      LC-TOFMS data was thoroughly compared to evaluate the strengths and shortcomings
      of FTIR biospectroscopy for assessing sample preparation in metabolomics studies.
      Results obtained show the feasibility of ATR-FTIR for the evaluation of major
      trends in the plasma composition changes among different sample pretreatments,
      providing information in terms of e.g., amino acids, proteins, lipids and
      carbohydrates overall contents comparable to those found by LC-TOFMS. 

PMID- 24913875
TI  - Analysis of the endogenous human serum peptides by on-line extraction with
      restricted-access material and HPLC-MS/MS identification.
AB  - The selective extraction of endogenous serum peptides has been a challenge due to
      the high abundant proteins present in serum. Here a simple on-line extraction of
      peptides from human serum using strong cation-exchange diol silica restricted
      access materials (SCX-RAM) coupled with two-dimensional RP-RP liquid
      chromatography mass spectrometry was developed. The operation of the on-line
      extraction system is simple to use and does not need complex equipments. The two
      dimensional RP-RP was proved to be orthogonal and efficient to separate peptides
      extracted from human serum. 

PMID- 24913876
TI  - Automatized sspKa measurements of dihydrogen phosphate and Tris(hydroxymethyl)
      aminomethane in acetonitrile/water mixtures from 20 to 60 degrees C.
AB  - We measured pKa values of Tris(hydroxymethyl)aminomethane and dihydrogen
      phosphate; both are commonly used to prepare buffers for reverse-phase liquid
      chromatography (RPLC), in acetonitrile/water mixtures from 0% to 70% (v/v) (64.6%
      (w/w)) acetonitrile and at 20, 30, 40, 50, and 60 degrees C. The procedure is
      based on potentiometric measurements of pH of buffer solutions of variable
      solvent compositions using a glass electrode and a novel automated system. The
      method consists in the controlled additions of small volumes of a thermostated
      solution from an automatic buret into another isothermal solution containing
      exactly the same buffer-component concentrations, but a different solvent
      composition. The continuous changes in the solvent composition induce changes in
      the potentials. Thus, only two sequences of additions are needed: increasing the
      amount of acetonitrile from pure water and decreasing the content of acetonitrile
      from 70% (v/v) (64.6% (w/w)). In the procedure with homemade apparatus, times for
      additions, stirring, homogenization, and data acquisition are entirely controlled
      by software programmed for this specific routine. This rapid, fully automated
      method was applied to acquire more than 40 potential data covering the whole
      composition range (at each temperature) in about two hours and allowed a
      systematic study of the effect of temperature and acetonitrile composition on
      acid-base equilibria of two widely used substances to control pH close to 7. The
      experimental pKa results were fitted to empirical functions between pKa and
      temperature and acetonitrile composition. These equations allowed predictions of
      pKa to estimate the pH of mixtures at any composition and temperature, which
      would be very useful, for instance, during chromatographic method development. 

PMID- 24913877
TI  - Second order multivariate curve resolution of Fourier transform infrared
      spectroscopic data of the photo-induced crosslinking of thymine functionalized
      polymers.
AB  - A meaningful characterization of the photo-induced curing process of materials
      based on styrene monomers functionalized with thymine and charged ionic groups
      was accomplished using FT-IR spectroscopy in combination with second-order
      multivariate calibration algorithms. The polymer composition as well as the
      irradiation dose effects on the photo-crosslinking of copolymer films was
      experimentally determined. Each FT-IR absorption spectra was decomposed into the
      contribution of individual species by means of chemometric algorithms. A second
      order strategy involving a three-way array for each sample and analyzing all
      arrays simultaneously was used. Temperature and solvent frequently have a strong
      influence on the FT-IR peak producing shifts and trilinearity lost. A new
      methodology to properly pre-align the spectroscopic matrix data is used based on
      the decomposition of a three-way array via a suitably initialized and constrained
      PARAFAC model. The chemical reaction mechanism describing the underlying process
      in terms of identifiable steps was determined. Associated key parameters and
      equilibrium rate constants that characterize the interconversion and stability of
      diverse species were predicted. Additionally, it was possible to quantify all the
      species even in the presence of a non-calibrated compound. 

PMID- 24913878
TI  - Applications of electrochemical techniques in mineral analysis.
AB  - This review, covering reports published in recent decade from 2004 to 2013, shows
      how electrochemical (EC) techniques such as voltammetry, electrochemical
      impedance spectroscopy, potentiometry, coulometry, etc., have made significant
      contributions in the analysis of minerals such as clay, sulfide, oxide, and
      oxysalt. It was discussed based on the classifications of both the types of the
      used EC techniques and kinds of the analyzed minerals. Furthermore, minerals as
      electrode modification materials for EC analysis have also been summarized.
      Accordingly, research vacancies and future development trends in these areas are
      discussed. 

PMID- 24913879
TI  - Application of partially fluorinated carboxylic acids as ion-pairing reagents in
      LC/ESI-MS.
AB  - This report describes the application of partially fluorinated carboxylic acids
      as ion-pairing reagents for basic analytes in high-performance liquid
      chromatography coupled with electrospray ionization mass spectrometry (LC/ESI-MS)
      in positive-ion mode. Partially fluoridated carboxylic acids such as
      difluoroacetic acid, 3,3,3-trifluoropropionic acid and 3,3,3-trifluoromethyl-2
      trifluoromethylpropionic acid functioned as volatile paired-ion similarly as
      trifluoroacetic acid (TFA). These acids provided basic analytes larger retention
      factor (k) compared to acetic acid or formic acid in LC. The ESI-MS signal
      strength of analytes with these acids were higher than that of TFA and was
      analogous to that of acetic acid or formic acid. The performances of partially
      fluorinated carboxylic acids in LC and ESI-MS for basic analytes were analyzed by
      multivariate statistical analysis using physicochemical descriptors of acids.
      Equations obtained in the analysis enabled us the quantitative evaluation of the
      performance of fluorinated carboxylic acids as ion-pair reagents for basic
      analytes in LC/ESI-MS. 

PMID- 24913880
TI  - Rational development and validation of a new microbiological assay for linezolid
      and its measurement uncertainty.
AB  - The aim of this work was to develop and validate a new microbiological assay to
      determine potency of linezolid in injectable solution. 2(4) factorial and central
      composite designs were used to optimize the microbiological assay conditions. In
      addition, we estimated the measurement uncertainty based on residual error of
      analysis of variance of inhibition zone diameters. Optimized conditions employed
      4 mL of antibiotic 1 medium inoculated with 1% of Staphylococcus aureus
      suspension, and linezolid in concentrations from 25 to 100 ug mL(-1). The method
      was specific, linear (Y=10.03X+5.00 and Y=9.20X+6.53, r(2)=0.9950 and 0.9987, for
      standard and sample curves, respectively), accurate (mean recovery=102.7%),
      precise (repeatability=2.0% and intermediate precision=1.9%) and robust.
      Microbiological assay's overall uncertainty (3.1%) was comparable to those
      obtained for other microbiological assays (1.7-7.1%) and for determination of
      linezolid by spectrophotometry (2.1%) and reverse-phase ultra-performance liquid
      chromatography (RP-UPLC) (2.5%). Therefore, it is an acceptable alternative
      method for the routine quality control of linezolid in injectable solution.

PMID- 24913881
TI  - Combination of capillary micellar liquid chromatography with on-chip microfluidic
      chemiluminescence detection for direct analysis of buspirone in human plasma.
AB  - Microfluidic based chemiluminescence (CL) detector having novel channel design
      for enhanced mixing has been developed and investigated in terms of its
      applicability with micellar mode of liquid chromatography (MLC). The newly
      developed detector was found to be highly sensitive and an alternative detection
      technique to combine with capillary MLC. This combination was successfully
      employed for direct detection of a model analyte using Ru(III)-peroxydisulphate
      CL system. The selected analyte, buspirone hydrochloride (BUS), was detected
      selectively at therapeutic concentration levels in human plasma without any
      sample pretreatment. By incorporating eight flow split units within the spiral
      channel of microfluidic chip, an enhancement of 140% in CL emission was observed.
      We also evaluated the effect of non- ionic surfactant, Brij-35, which used as
      mobile phase modifier in MLC, on CL emission. The CL signal was improved by 52%
      compared to aqueous-organic mobile phase combinations. Various parameters
      influencing the micellar chromatographic performance and the CL emission were
      optimized. This allowed highly sensitive analysis of BUS with limit of detection
      (LOD) of 0.27 ng mL(-1) (3sigma/s) and limit of quantification (LOQ) of 0.89 ng
      mL(-1) (10sigma/s). The analyte recovery from human plasma at three different
      concentration level ranges from 88% to 96% (RSD 1.9-5.3%). The direct analysis of
      BUS in human plasma was achieved within 6 min. Therefore, combining microfluidic
      CL detection with micellar mode of separation is an efficient, cost-effective and
      highly sensitive technique that can utilize MLC in its full capacity for various
      bioanalytical procedures.

PMID- 24913882
TI  - Using corona discharge-ion mobility spectrometry for detection of 2,4,6
      Trichloroanisole.
AB  - In this work possible application of the corona discharge-ion mobility
      spectrometer (CD-IMS) for detection of 2,4,6-Trichloroanisole (TCA) has been
      investigated. We applied CD-IMS interfaced with orthogonal acceleration time of
      flight mass spectrometer (CD-IMS-oaTOF) to study the ion processes within the CD
      IMS technique. The CD-IMS instrument was operated in two modes, (i) standard and
      (ii) reverse flow modes resulting in different chemical ionisation schemes by
      NO3(-)(HNO3)n (n=0,1,2) and O2(-)(H2O)n (n=0,1,2), respectively. The O2(-)(H2O)n
      ionisation was associated with formation of Cl(-) and (TCA-CH3)(-) ions from TCA.
      The NO3(-)(HNO3)n ionisation, resulted in formation of NO3(-)(HNO3)(TCA-Cl)
      adduct ions. Limit of detection (LOD) for TCA was determined in gas (100 ppb) and
      solid phases (150 ng).

PMID- 24913883
TI  - Sequential determination of lead and cobalt in tap water and foods samples by
      fluorescence.
AB  - In this work, a new procedure was developed for the separation and
      preconcentration of lead(II) and cobalt(II) in several water and foods samples.
      Complexes of metal ions with 8-hydroxyquinolein (8-HQ) were formed in aqueous
      solution. The proposed methodology is based on the preconcentration/separation of
      Pb(II) by solid-phase extraction using paper filter, followed by
      spectrofluorimetric determination of both metals, on the solid support and the
      filtered aqueous solution, respectively. The solid surface fluorescence
      determination was carried out at lambdaem=455 nm (lambdaex=385 nm) for Pb(II)-8
      HQ complex and the fluorescence of Co(II)-8-HQ was determined in aqueous solution
      using lambdaem=355 nm (lambdaex=225 nm). The calibration graphs are linear in the
      range 0.14-8.03*10(4) MUg L(-1) and 7.3*10(-2)-4.12*10(3) MUg L(-1), for Pb(II)
      and Co(II), respectively, with a detection limit of 4.3*10(-2) and 2.19*10(-2)
      MUg L(-1) (S/N=3). The developed methodology showed good sensitivity and adequate
      selectivity and it was successfully applied to the determination of trace amounts
      of lead and cobalt in tap waters belonging of different regions of Argentina and
      foods samples (milk powder, express coffee, cocoa powder) with satisfactory
      results. The new methodology was validated by electrothermal atomic absorption
      spectroscopy with adequate agreement. The proposed methodology represents a novel
      application of fluorescence to Pb(II) and Co(II) quantification with sensitivity
      and accuracy similar to atomic spectroscopies.

PMID- 24913884
TI  - Determination of traces of Pt and Rh in soil and quartz samples contaminated by
      automobile exhaust after an ion-exchange matrix separation.
AB  - Monitoring of PGEs content in the natural samples is a crucial point in the
      environment science since catalytic car converters have been introduced. In the
      presented paper application of a very sensitive voltammetric method for
      determination of traces of Pt and Rh in the environmental samples contaminated by
      automobile exhausts is discussed. Voltammetric measurements were carried out in
      the supporting electrolyte containing formaldehyde and semicarbazide. PGEs were
      separated from the digested solutions of soils or quartz samples, collected from
      monitoring plots-by applying an ion-exchange resin Cellex-T. Pt was very
      effectively separated from the matrix approaching nearly 100% recovery after its
      elution by hydrochloric acid. Moreover the conditions of soil and quartz samples
      digestion were discussed. To validate the obtained result an independent
      analytical method-ICP MS was applied and analysis of certified reference material
      road dust 723-was completed. 

PMID- 24913885
TI  - An electrochemical sensor for simultaneous determination of ascorbic acid,
      dopamine, uric acid and tryptophan based on MWNTs bridged mesocellular graphene
      foam nanocomposite.
AB  - A multi-walled carbon nanotubes (MWNTs) bridged mesocellular graphene foam (MGF)
      nanocomposite (MWNTs/MGF) modified glassy carbon electrode was fabricated and
      successfully used for simultaneous determination of ascorbic acid (AA), dopamine
      (DA), uric acid (UA) and tryptophan (TRP). Comparing with pure MGF, MWNTs or
      MWNTs/GS (graphene sheets), MWNTs/MGF displayed higher catalytic activity and
      selectivity toward the oxidation of AA, DA, UA and TRP. Under the optimal
      conditions, MWCNs/MGF/GCE can simultaneously detect AA, DA, UA and TRP with high
      selectivity and sensitivity. The detection limits were 18.28 umol L(-1), 0.06
      umol L(-1), 0.93 umol L(-1) and 0.87 umol L(-1), respectively. Moreover, the
      modified electrode exhibited excellent stability and reproducibility.

PMID- 24913887
TI  - Polystyrene/Ag nanoparticles as dynamic surface-enhanced Raman spectroscopy
      substrates for sensitive detection of organophosphorus pesticides.
AB  - We report the use of Polystyrene/Ag (PS/Ag) nanoparticles as dynamic surface
      enhanced Raman spectroscopy (dynamic-SERS) substrates for sensitive detection of
      low levels of organophosphorus pesticides. The PS particles clearly observed
      using Raman microscopy provide the masterplate for in situ growth of Ag NPs,
      leading to multiple active sites for SERS measurements. Besides obtaining the
      fingerprints of target molecules and recording time-resolved Raman spectra, this
      dynamic-SERS method can be used as an ultra-sensitive analytical technique which
      can enhance 1-2 orders of magnitude the signals of analytes in comparison to that
      of the traditional methods. On the other hand, importantly, it shows much better
      correlations between concentration and intensity than does the conventional SERS
      technique so that it can build the foundation for quantitative analysis of
      analytes. The as-prepared individual PS/Ag nanoparticle has been demonstrated for
      the sensitive detection of organophosphorus paraoxon and sumithion. SERS spectra
      are acquired at different concentrations of each pesticide and linear calibration
      curves are obtained by monitoring the strongest intensity value of bands arising
      from stronger stretching mode as a function of analyte concentration. The limits
      of detection and limits of quantitation are reported for two pesticides. The
      limit of detection for paraoxon is 96 nM (0.026 ppm) and for sumithion is 34 nM
      (0.011 ppm). The limits of quantitation are 152 nM (0.042 ppm) and 57 nM (0.016
      ppm) for paraoxon and sumithion, respectively. It can be seen that these two
      organophosphorus pesticides can be detected in the low nM range based on this
      dynamic-SERS analytical method. Also, in the real sample experiments of paraoxon
      and sumithion, the results confirm that this dynamic-SERS technique would have
      potential applicability for quantitative analysis with slight interference.

PMID- 24913886
TI  - An electrochemical sensor based on polyaniline for monitoring hydroquinone and
      its damage on DNA.
AB  - A dsDNA/PANI/CTS/GCE biosensor was constructed by using the biocompatible
      chitosan (CTS) and the polyaniline (PANI) with excellent electric catalytic
      properties and large specific surface areas. The electrochemical behavior of
      hydroquinone on biosensor and its DNA-damaging mechanisms were investigated.
      Results showed that the redox peak current was remarkably increased after glassy
      carbon electrode (GCE) was modified by PANI/CTS. The dsDNA damage by hydroquinone
      was concentration dependent, and increased along with the increase of
      hydroquinone oxidation peak current and the reduction of dsDNA guanine oxidation
      peak current. The linear detection range of hydroquinone with dsDNA/PANI/CTS/GCE
      was 1.25*10(-6)-3.2*10(-4) M, and the detection limit was 9.65*10(-7) M. It was
      confirmed by the UV method that applying dsDNA/PANI/CTS/GCE to monitor
      hydroquinone was accurate and reliable. In addition, it could be deduced that the
      mode of interaction between the hydroquinone and dsDNA was intercalation. The
      electrochemical oxidation of hydroquinone on the dsDNA/PANI/CTS/GCE electrode was
      an adsorption-controlled irreversible and a two-electron two-proton transfer
      process.

PMID- 24913888
TI  - Mechanism of a novel missense mutation, p.V174M, of the human connexin31 (GJB3)
      in causing nonsyndromic hearing loss.
AB  - Hearing loss is the most common sensory disorder, worldwide. In a recent study,
      we have identified a missense mutation, p.V174M, in the connexin 31 encoded by
      the GJB3 gene, in a patient with nonsyndromic hearing loss. However, the
      functional change in the CX31V174M mutant remains unknown. This study compared
      the intracellular distribution and assembly of the mutant CX31V174M with that of
      the wild-type (WT) CX31 in HeLa cells, and it examined the effect that the mutant
      protein had on those cells. A fluorescent localization assay of WT CX31 showed
      the typical punctuate pattern of a gap junction channel between the neighboring
      expression cells. Conversely, the p.V174M missense mutation resulted in the
      accumulation of the mutant protein in the lysosomes rather than in the
      cytoplasmic membrane. Moreover, dye transfer experiments have also demonstrated
      that the CX31V174M mutant did not form functional gap junction channels, probably
      due to the incorrect assembly or the altered properties of the CX31 channels. In
      addition, we found that CX31V174M-transfection can cause cell death by MTT assay.
      CX31V174M co-expressed with either CX31WT or CX26WT studies, suggested the
      impairment of the ability of CX26WT proteins to intracellular trafficking and
      targeting to the plasma membrane, but did not influence the trafficking of
      CX31WT. Based on these findings, we suggest that the CX31V174M mutant may have an
      effect on the formation and function of the gap junction, and CX31V174M has a
      trans-dominant negative effect on the function of wild types CX26. These results
      provide a novel molecular explanation for the role that GJB3 plays in hearing
      loss. 

PMID- 24913889
TI  - Archives of total mercury reconstructed with ice and snow from Greenland and the
      Canadian High Arctic.
AB  - This study reports total Hg concentration and atmospheric flux data from ice
      cores and snow/ice shallow pits from two Canadian Arctic and one Greenland
      glaciers, with the aim of reconstructing a high resolution record of THg
      deposition extending back into the pre-industrial period. An 88-m ice core (653
      samples) from the NEEM glacier site in Northwest Greenland was retrieved in
      August 2010. The bottom sample was dated to 1748, resulting in a 262 year
      archive. Snow and ice samples (143 samples) were recovered from a 10.3-m pit dug
      on the Mt. Oxford Icefield, Nunavut, in May 2008, covering 30 years. Another 15.5
      m short core drilled on the Agassiz Ice Cap, Nunavut, in April 2009 yielded 191
      samples covering 74 years. Net rates of atmospheric THg deposition (FTHg) were
      calculated based on THg concentrations and snow accumulation rates. Results from
      NEEM site show that THg and FTHg range from sub-pg g(-1) to 120.6 pg g(-1)
      (mean=1.5 pg g(-1), n=653) and from 0.06 to 1.42 MUg m(-2) year(-1) (mean=0.25
      MUg m(-2) year(-1), n=218) respectively, much lower than those found in other
      natural media such as sediments, peat bogs and wet precipitation. The discrepancy
      of FTHg found in glaciers from other natural media could mainly be due to the
      more severe photo-reduction and reemission of deposited oxidized Hg. This study
      also demonstrates that reproducible THg archives can be reconstructed with
      glacier ice and snow samples from Greenland and the Canadian High Arctic. The THg
      archive reconstructed with the short core from NEEM site is so far the longest
      with the highest resolution in Greenland and the Canadian High Arctic.

PMID- 24913890
TI  - Designing a high-yielding maize ideotype for a changing climate in Lombardy plain
      (northern Italy).
AB  - The expected climate change will affect the maize yields in view of air
      temperature increase and scarce water availability. The application of
      biophysical models offers the chance to design a drought-resistant ideotype and
      to assist plant breeders and agronomists in the assessment of its suitability in
      future scenarios. The aim of the present work was to perform a model-based
      estimation of the yields of two hybrids, current vs ideotype, under future
      climate scenarios (2030-2060 and 2070-2100) in Lombardy (northern Italy), testing
      two options of irrigation (small amount at fixed dates vs optimal water supply),
      nitrogen (N) fertilization (300 vs 400 kg N ha(-1)), and crop cycle durations
      (current vs extended). For the designing of the ideotype we set several
      parameters of the ARMOSA process-based crop model: the root elongation rate and
      maximum depth, stomatal resistance, four stage-specific crop coefficients for the
      actual transpiration estimation, and drought tolerance factor. The work findings
      indicated that the current hybrid ensures good production only with high
      irrigation amount (245-565 mm y(-1)). With respect to the current hybrid, the
      ideotype will require less irrigation water (-13%, p<0.01) and it resulted in
      significantly higher yield under water stress condition (+15%, p<0.01) and
      optimal water supply (+2%, p<0.05). The elongated cycle has a positive effect on
      yield under any combination of options. Moreover, higher yields projected for the
      ideotype implicate more crop residues to be incorporated into the soil, which are
      positively correlated with the SOC sequestration and negatively with N leaching.
      The crop N uptake is expected to be adequate in view of higher rate of soil
      mineralization; the N fertilization rate of 400 kg N ha(-1) will involve
      significant increasing of grain yield, and it is expected to involve a higher
      rate of SOC sequestration.

PMID- 24913891
TI  - Flexible energy-storage devices: design consideration and recent progress.
AB  - Flexible energy-storage devices are attracting increasing attention as they show
      unique promising advantages, such as flexibility, shape diversity, light weight,
      and so on; these properties enable applications in portable, flexible, and even
      wearable electronic devices, including soft electronic products, roll-up
      displays, and wearable devices. Consequently, considerable effort has been made
      in recent years to fulfill the requirements of future flexible energy-storage
      devices, and much progress has been witnessed. This review describes the most
      recent advances in flexible energy-storage devices, including flexible lithium
      ion batteries and flexible supercapacitors. The latest successful examples in
      flexible lithium-ion batteries and their technological innovations and challenges
      are reviewed first. This is followed by a detailed overview of the recent
      progress in flexible supercapacitors based on carbon materials and a number of
      composites and flexible micro-supercapacitors. Some of the latest achievements
      regarding interesting integrated energy-storage systems are also reviewed.
      Further research direction is also proposed to surpass existing technological
      bottle-necks and realize idealized flexible energy-storage devices. 

PMID- 24913892
TI  - Spatial relationship between the mental foramen and mandibular developing teeth
      in modern humans, chimpanzees, and hamadryas baboons.
AB  - The mental foramen (MF) of adult human mandibles is characterized by its high
      position and posterosuperior opening orientation, compared with that of nonhuman
      primates. In this study, to examine when and how such interspecies variations in
      MF position/orientation are manifested in the context of dental development,
      positional relationships between the MF and nearby forming teeth (dc, dm1, C, P3)
      were assessed using CT-scanned growth-series mandibles of the following three
      species with various MF positions and anterior dental sizes: modern humans,
      chimpanzees, and hamadryas baboons. Results showed that modern humans have more
      antero-superiorly located MF and dc than the two nonhuman samples during growth,
      whereas the MF and dm1 of hamadryas baboons are the most inferiorly positioned.
      Considering that the mandibular canal generally reaches the dc/dm1 position
      during infancy, the species differences in MF position can be attributed largely
      to the positions where the anterior deciduous teeth first appear. Specifically,
      the distinctive dental position of modern humans should stem eventually from the
      comparatively small anterior dental size. Furthermore, human MF position shifted
      slightly upwards with alveolar development, unlike in the nonhuman samples,
      accompanied by strong curvature and vertical elongation of the anterior
      mandibular canal. Meanwhile, the human MF shifted from a forward to a
      lateral/backward orientation in association with human-specific growth-related
      alveolar recession. The findings of this study, thus, collectively indicate that
      taxonomic variations in adult MF position/orientation can be interpreted partly
      by the positions of the surrounding developing teeth.

PMID- 24913893
TI  - Generation and characterization of Neurod1-CreER(T2) mouse lines for the study of
      embryonic and adult neurogenesis.
AB  - Neurod1 is a transcription factor involved in several developmental programs of
      the gastrointestinal tract, pancreas, neurosensory, and central nervous system.
      In the brain, Neurod1 has been shown to be essential for neurogenesis as well as
      migration, maturation, and survival of newborn neurons during development and
      adulthood. Interestingly, Neurod1 expression is maintained in a subset of fully
      mature neurons where its function remains unclear. To study the role of Neurod1,
      systems are required that allow the temporal and spatial genetic manipulation of
      Neurod1-expressing cells. To this aim, we have generated four Neurod1-CreER(T2)
      mouse lines in which CreER(T2) expression, although at different levels, is
      restricted within areas of physiological Neurod1 expression and Neurod1 positive
      cells. In particular, the different levels of CreER(T2) expression in different
      mouse lines offers the opportunity to select the one that is more suited for a
      given experimental approach. Hence, our Neurod1-CreER(T2) lines provide valuable
      new tools for the manipulation of newborn neurons during development and
      adulthood as well as for studying the subpopulation of mature neurons that retain
      Neurod1 expression throughout life. In this context, we here report that Neurod1
      is not only expressed in immature newborn neurons of the adult hippocampus, as
      already described, but also in fully mature granule cells of the dentate gyrus.

PMID- 24913894
TI  - Low-copper diet as a preventive strategy for Alzheimer's disease.
AB  - Copper is an essential element, and either a copper deficiency or excess can be
      life threatening. Recent studies have indicated that alteration of copper
      metabolism is one of the pathogenetic mechanisms of Alzheimer's disease (AD). In
      light of these findings, many researchers have proposed preventive strategies to
      reduce AD risk. Because the general population comes in contact with copper
      mainly through dietary intake, that is, food 75% and drinking water 25%, a low
      copper diet can reduce the risk of AD in individuals with an altered copper
      metabolism. We suggest that a diet-gene interplay is at the basis of the "copper
      phenotype" of sporadic AD. Herein, we describe the pathways regulating copper
      homeostasis, the adverse sequelae related to its derangements, the pathogenic
      mechanism of the AD copper phenotype, indications for a low-copper diet, and
      future perspectives to improve this preventive strategy. 

PMID- 24913895
TI  - Cognition and hippocampal synaptic plasticity in mice with a homozygous tau
      deletion.
AB  - Tau has been implicated in the organization, stabilization, and dynamics of
      microtubules. In Alzheimer's disease and more than 20 neurologic disorders tau
      missorting, hyperphosphorylation, and aggregation is a hallmark. They are
      collectively referred to as tauopathies. Although the impact of human tauopathies
      on cognitive processes has been explored in transgenic mouse models, the
      functional consequences of tau deletion on cognition are far less investigated.
      Here, we subjected tau knock-out (KO) mice to a battery of neurocognitive,
      behavioral, and electrophysiological tests. Although KO and wild-type mice were
      indistinguishable in motor abilities, exploratory and anxiety behavior, KO mice
      showed impaired contextual and cued fear conditioning. In contrast, extensive
      spatial learning in the water maze resulted in better performance of KO mice
      during acquisition. In electrophysiological experiments, basal synaptic
      transmission and paired-pulse facilitation in the hippocampal CA1-region were
      unchanged. Interestingly, deletion of tau resulted in severe deficits in long
      term potentiation but not long-term depression. Our results suggest a role of tau
      in certain cognitive functions and implicate long-term potentiation as the
      relevant physiological substrate. 

PMID- 24913896
TI  - Dietary and lifestyle guidelines for the prevention of Alzheimer's disease.
AB  - Risk of developing Alzheimer's disease is increased by older age, genetic
      factors, and several medical risk factors. Studies have also suggested that
      dietary and lifestyle factors may influence risk, raising the possibility that
      preventive strategies may be effective. This body of research is incomplete.
      However, because the most scientifically supported lifestyle factors for
      Alzheimer's disease are known factors for cardiovascular diseases and diabetes,
      it is reasonable to provide preliminary guidance to help individuals who wish to
      reduce their risk. At the International Conference on Nutrition and the Brain,
      Washington, DC, July 19-20, 2013, speakers were asked to comment on possible
      guidelines for Alzheimer's disease prevention, with an aim of developing a set of
      practical, albeit preliminary, steps to be recommended to members of the public.
      From this discussion, 7 guidelines emerged related to healthful diet and exercise
      habits. 

PMID- 24913897
TI  - Default mode network as a potential biomarker of chemotherapy-related brain
      injury.
AB  - Chronic medical conditions and/or their treatments may interact with aging to
      alter or even accelerate brain senescence. Adult onset cancer, for example, is a
      disease associated with advanced aging and emerging evidence suggests a profile
      of subtle but diffuse brain injury following cancer chemotherapy. Breast cancer
      is currently the primary model for studying these "chemobrain" effects. Given the
      widespread changes to brain structure and function as well as the common
      impairment of integrated cognitive skills observed following breast cancer
      chemotherapy, it is likely that large-scale brain networks are involved. Default
      mode network (DMN) is a strong candidate considering its preferential
      vulnerability to aging and sensitivity to toxicity and disease states.
      Additionally, chemotherapy is associated with several physiological effects
      including increased inflammation and oxidative stress that are believed to
      elevate toxicity in the DMN. Biomarkers of DMN connectivity could aid in the
      development of treatments for chemotherapy-related cognitive decline. 

PMID- 24913898
TI  - Antibody-based imaging strategies for cancer.
AB  - Although mainly developed for preclinical research and therapeutic use,
      antibodies have high antigen specificity, which can be used as a courier to
      selectively deliver a diagnostic probe or therapeutic agent to cancer. It is
      generally accepted that the optimal antigen for imaging will depend on both the
      expression in the tumor relative to normal tissue and the homogeneity of
      expression throughout the tumor mass and between patients. For the purpose of
      diagnostic imaging, novel antibodies can be developed to target antigens for
      disease detection, or current FDA-approved antibodies can be repurposed with the
      covalent addition of an imaging probe. Reuse of therapeutic antibodies for
      diagnostic purposes reduces translational costs since the safety profile of the
      antibody is well defined and the agent is already available under conditions
      suitable for human use. In this review, we will explore a wide range of
      antibodies and imaging modalities that are being translated to the clinic for
      cancer identification and surgical treatment. 

PMID- 24913899
TI  - Obesity and mortality: are the risks declining? Evidence from multiple
      prospective studies in the United States.
AB  - We evaluated whether the obesity-associated years of life lost (YLL) have
      decreased over calendar time. We implemented a meta-analysis including only
      studies with two or more serial body mass index (BMI) assessments at different
      calendar years. For each BMI category (normal weight: BMI 18.5 to <25
      [reference]; overweight: BMI 25 to <30; grade 1 obesity: BMI 30 to <35; and grade
      2-3 obesity: BMI >= 35), we estimated the YLL change between 1970 and 1990.
      Because of low sample sizes for African-American, results are reported on
      Caucasian. Among men aged <=60 years YLL for grade 1 obesity increased by 0.72
      years (P < 0.001) and by 1.02 years (P = 0.01) for grade 2-3 obesity. For men
      aged >60, YLL for grade 1 obesity decreased by 1.02 years (P < 0.001) and
      increased by 0.63 years for grade 2-3 obesity (P = 0.63). Among women aged <=60,
      YLL for grade 1 obesity decreased by 4.21 years (P < 0.001) and by 4.97 years (P
      < 0.001) for grade 2-3 obesity. In women aged >60, YLL for grade 1 obesity
      decreased by 3.98 years (P < 0.001) and by 2.64 years (P = 0.001) for grade 2-3
      obesity. Grade 1 obesity's association with decreased longevity has reduced for
      older Caucasian men. For Caucasian women, there is evidence of a decline in the
      obesity YLL association across all ages. 

PMID- 24913900
TI  - Effects of the combined substitutions of amino acid residues on thermal
      properties of cold-adapted monomeric isocitrate dehydrogenases from psychrophilic
      bacteria.
AB  - In the two cold-adapted monomeric isocitrate dehydrogenases from psychrophilic
      bacteria, Colwellia maris and Colwellia psychrerythraea (CmIDH and CpIDH,
      respectively), the combined substitutions of amino acid residues between the
      Leu693, Leu724 and Phe735 residues of CmIDH and the corresponding Phe693, Gln724
      and Leu735 residues of CpIDH were introduced by site-directed mutagenesis. A
      double mutant of CmIDH substituted its Leu724 and Phe735 residues by the
      corresponding ones of CpIDH, CmL724Q/F735L, and the triple mutant of CpIDH,
      CpF693L/Q724L/L735F, showed the most decrease and increase of activity,
      respectively, of each wild-type and its all mutated enzymes. In the case of
      CmIDH, the substitutions of these three amino acid residues resulted in the
      decrease of catalytic activity and thermostability for activity, but the combined
      substitutions of amino acid residues did not necessarily exert additive effects
      on these properties. On the other hand, similar substitutions in CpIDH had quite
      opposite effects to CmIDH, and the effects of the combined substitutions were
      additive. All multiple mutants of CmIDH and CpIDH showed lower and higher
      catalytic efficiency (k(cat)/K(m)) values than the respective wild-type enzymes.
      Single and multiple mutations of the substituted amino acid residues in the CmIDH
      and CpIDH led to the increase and decrease of sensitivity to tryptic digestion,
      indicating that the stability of protein structure was decreased and increased by
      the mutations, respectively.

PMID- 24913901
TI  - A systematic strain selection approach for halotolerant and halophilic bioprocess
      development: a review.
AB  - Halotolerant and halophilic microorganisms have potential applications in a
      number of very relevant environmental and industrial bioprocesses, from
      wastewater treatment to production of value-added chemicals. While numerous
      microbial strains have been identified and studied in the literature, the number
      of those successfully used in industrial applications is comparatively small.
      Literature is abundant in terms of characterisation of specific strains under a
      microbiology perspective; however, there is a need for studies tackling the
      selection of strains for bioprocess applications. This review presents a database
      of over 200 halophilic and halotolerant prokaryote strains compiled from
      taxonomic microbiological resources and classified by trophic groups as well as
      by their salinity, pH and temperature tolerance and optimum ranges, all under a
      process development perspective. In addition to this database, complementary
      systematic approaches for the selection of suitable strains for a given trophic
      activity and environmental conditions are also presented. Both the database and
      the proposed selection approaches together constitute a general tool for process
      development that allows researchers to systematically search for strains capable
      of specific substrate degradations under specific conditions (pH, T, salinity).
      Many exiting established halotolerant and halophilic environmental and industrial
      bioprocesses appear to have been developed following strategies in line with the
      systematic approaches proposed here. 

PMID- 24913903
TI  - Affective topic model for social emotion detection.
AB  - The rapid development of social media services has been a great boon for the
      communication of emotions through blogs, microblogs/tweets, instant-messaging
      tools, news portals, and so forth. This paper is concerned with the detection of
      emotions evoked in a reader by social media. Compared to classical sentiment
      analysis conducted from the writer's perspective, analysis from the reader's
      perspective can be more meaningful when applied to social media. We propose an
      affective topic model with the intention to bridge the gap between social media
      materials and a reader's emotions by introducing an intermediate layer. The
      proposed model can be used to classify the social emotions of unlabeled documents
      and to generate a social emotion lexicon. Extensive evaluations using real-world
      data validate the effectiveness of the proposed model for both these
      applications. 

PMID- 24913904
TI  - Rhabdomyosarcoma arising in a giant congenital melanocytic nevus.
AB  - A number of lesions have been documented to arise within congenital melanocytic
      nevi (CMNs). Although the most frequent malignancy arising within a CMN is
      melanoma, the association between rhabdomyosarcoma and CMN has rarely been
      documented. We present a case arising in a 4-month-old girl with a giant CMN. She
      presented for evaluation of a pedunculated lesion at the superior gluteal crease
      that had been present since birth and exhibited rapid growth. Biopsy of the
      lesion revealed two distinct components: an expansile proliferation of
      pleomorphic cells with varying degrees of cellularity and a proliferation of
      banal-appearing melanocytic nevic cells. The cells of the expansile proliferation
      displayed a wide range of morphologic features, including nests of round cells,
      spindle-shaped cells, and more differentiated rhabdomyoblasts within a myxoid,
      highly vascularized stroma. Cross-striations, a marker of skeletal muscle
      differentiation, were present. These tumor cells were strongly immunoreactive
      with desmin, myo-D1, and myogenin. Fluorescence in situ hybridization analysis
      with PAX3/7-FKHR probes was negative. A diagnosis of embryonal rhabdomyosarcoma
      in association with CMN was made. Initial excision revealed tumor at the margins,
      and the patient underwent reexcision with subsequent chemotherapy with
      vincristine, actinomycin D, and cyclophosphamide. She was disease-free at the 6
      year follow-up. It has been postulated that the combination of melanocytic and
      rhabdomyoblastic cells within the same lesion may imply derivation from a common
      pluripotent stem cell or neural crest cell. Clinicians following patients with
      giant CMN should consider rhabdomyosarcoma in the differential diagnosis of
      lesions arising within the nevus. 

PMID- 24913905
TI  - Characterization of physical and chemical defenses in the hemlock woolly adelgid.
AB  - The invasive hemlock woolly adelgid (Adelges tsugae Annand, Hemiptera:
      Sternorrhyncha: Adelgidae) causes significant mortality to eastern and Carolina
      hemlock (Tsuga canadensis Carriere and T. caroliniana Engelmann, respectively)
      throughout the eastern United States. Adelges tsugae produces vast quantities of
      a wax covering that surrounds most of the instars as well as the adult and eggs.
      Using direct probe EI mass spectrometry, this wax covering was characterized as a
      diketoester wax, 17-oxohexatriacontanyl 11-oxotriacontanoate, and accounted for ~
      42 % of A. tsugae total biomass. The presence of the anthraquinone, chrysophanol,
      and its precursor anthrone, chrysarobin, in A. tsugae has only been briefly
      described. Further study confirmed these compounds in all A. tsugae life stages.
      Additionally, several predatory beetles in use or under consideration as
      biological control agents for this species appear to ingest and excrete these
      compounds when feeding on A. tsugae. The production of both a physical and a
      chemical defense may represent a significant energy investment by A. tsugae. 

PMID- 24913902
TI  - White paper of Italian Gastroenterology: delivery of services for digestive
      diseases in Italy: weaknesses and strengths.
AB  - In 2011 the three major Italian gastroenterological scientific societies (AIGO,
      the Italian Society of Hospital Gastroenterologists and Endoscopists; SIED, the
      Italian Society of Endoscopy; SIGE, the Italian Society of Gastroenterology)
      prepared their official document aimed at analysing medical care for digestive
      diseases in Italy, on the basis of national and regional data (Health Ministry
      and Lombardia, Veneto, Emilia-Romagna databases) and to make proposals for
      planning of care. Digestive diseases were the first or second cause of
      hospitalizations in Italy in 1999-2009, with more than 1,500,000 admissions/year;
      however only 5-9% of these admissions was in specialized Gastroenterology units.
      Reported data show a better outcome in Gastroenterology Units than in non
      specialized units: shorter average length of stay, in particular for admissions
      with ICD-9-CM codes proxying for emergency conditions (6.7 days versus 8.4 days);
      better case mix (higher average diagnosis-related groups weight in
      Gastroenterology Units: 1 vs 0.97 in Internal Medicine units and 0.76 in Surgery
      units); lower inappropriateness of admissions (16-25% versus 29-87%); lower in
      hospital mortality in urgent admissions (2.2% versus 5.1%); for patients with
      urgent admissions due to gastrointestinnal haemorrhage, in-hospital mortality was
      2.3% in Gastroenterology units versus 4.0% in others. The present document
      summarizes the scientific societies' official report, which constitutes the
      "White paper of Italian Gastroenterology". 

PMID- 24913906
TI  - Study of MET protein levels and MET gene copy number in 72 sinonasal intestinal
      type adenocarcinomas.
AB  - BACKGROUND: Sinonasal intestinal-type adenocarcinomas (ITACs) have a poor
      prognosis, and are defined on the basis of their morphological similarities to
      colorectal adenocarcinomas. MET signaling pathway is involved in oncogenesis in
      various cancers. Nothing is currently known about the role of MET in ITACs.
      METHODS: In a series of 72 ITACs, we investigated MET protein levels by
      immunohistochemistry (IHC) and gene copy number by in situ hybridization. These
      findings were analyzed as a function of clinical data, histological typing, and
      patient outcome. RESULTS: MET protein was overproduced in 64% of cases and
      chromosome 7 polysomy was observed in 52% of cases. No tumor displayed MET
      amplification. The presence of mucinous or solid histological components, T3/T4
      tumors, and incomplete resection were associated with a poor outcome. CONCLUSION:
      MET is overproduced in about two third of ITACs, suggesting a role for the MET
      signaling pathway in the oncogenesis of these tumors.

PMID- 24913907
TI  - The optimal timing of continuous renal replacement therapy for patients with
      sepsis-induced acute kidney injury.
AB  - PURPOSE: High mortality in the intensive care unit (ICU) is probably associated
      with sepsis-induced acute kidney injury (AKI). The aim of this study is to
      explore which stage of AKI may be the optimal timing for continuous renal
      replacement therapy (CRRT). METHODS: A retrospective analysis of 160 critically
      ill patients with septic AKI, treated with or without CRRT was performed in
      Binzhou medical college affiliated hospital ICU. The parameters including 28-days
      mortality rate, renal recovery, ventilation time and ICU stay between CRRT group
      and control group were assessed. RESULTS: Renal recovery, defined as independence
      from dialysis at discharge, was documented for 64/76 (84.2 %) of the surviving
      patients (48.1 % of total subjects included in the study). The mortality rate
      increased proportionally with acute kidney injury Network stages in CRRT
      subgroups (P = 0.001) and control groups (P = 0.029). CRRT initiation at stage 2
      of AKI significantly reduced the 28-day mortality (P = 0.048) and increased the
      28-day survival rate (P = 0.036) compared with those in control group. In
      addition, the ICU stay and ventilation time were shorter in CRRT group than that
      of control group in stage 2 of AKI. CONCLUSION: The stage 2 AKI might be the
      optimal timing for performing CRRT.

PMID- 24913908
TI  - Differential co-expression analysis of a microarray gene expression profiles of
      pulmonary adenocarcinoma.
AB  - Lung cancer severely reduces the quality of life worldwide and causes high
      socioeconomic burdens. However, key genes leading to the generation of pulmonary
      adenocarcinoma remain elusive despite intensive research efforts. The present
      study aimed to identify the potential associations between transcription factors
      (TFs) and differentially co-expressed genes (DCGs) in the regulation of
      transcription in pulmonary adenocarcinoma. Gene expression profiles of pulmonary
      adenocarcinoma were downloaded from the Gene Expression Omnibus, and gene
      expression was analyzed using a computational method. A total of 37,094
      differentially co-expressed links (DCLs) and 251 DCGs were identified, which were
      significantly enriched in 10 pathways. The construction of the regulatory network
      and the analysis of the regulatory impact factors revealed eight crucial TFs in
      the regulatory network. These TFs regulated the expression of DCGs by promoting
      or inhibiting their expression. In addition, certain TFs and target genes
      associated with DCGs did not appear in the DCLs, which indicated that those TFs
      could be synergistic with other factors. This is likely to provide novel insights
      for research into pulmonary adenocarcinoma. In conclusion, the present study may
      enhance the understanding of disease mechanisms and lead to an improved diagnosis
      of lung cancer. However, further studies are required to confirm these
      observations. 

PMID- 24913909
TI  - Two distinct nuclear localization signals in mammalian MSL1 regulate its
      function.
AB  - MSL1 protein regulates global histone H4 acetylation at residue K16 in stem and
      cancer cells, through interaction with KAT8. The functional significance of
      mammalian MSL1 isoforms, involved in various protein interactions, is poorly
      understood. We report the identification of a novel nuclear localization signal
      (NLS), common to all MSL1 isoforms, in addition to previously known bipartite
      NLS, located in domain PEHE. Isoforms having both NLS localize to sub-nuclear
      foci where they can target co-chaperone protein TTC4. However, all MSL1 isoforms
      also have ability to affect H4K16 acetylation. Thus, presence of two NLS in MSL1
      protein can mediate activity of KAT8 in vivo.

PMID- 24913910
TI  - Aggressive estrogen-receptor-positive breast cancer arising in patients with
      elevated body mass index.
AB  - BACKGROUND: Obese women with estrogen receptor (ER)-positive breast cancer may
      experience worse disease-free and overall survival. We hypothesize that this
      observation is due to intrinsically aggressive disease and that obesity will be
      associated with higher histologic grade and Ki67. METHODS: A sequential cohort of
      women with breast cancer diagnosed over 2 years was assembled from institutional
      tumor registries. Patient and tumor characteristics were abstracted from medical
      records; those with non-invasive tumors, or lacking body mass index (BMI), Ki67
      or histologic grade data, were excluded. Univariate and multivariate analysis was
      performed to investigate the relationship between markers of aggressive disease
      (grade and Ki67) and multiple variables associated with obesity. A subgroup
      analysis was performed to investigate further whether ER and menopausal status
      influenced associations between BMI and aggressive phenotypes. RESULTS: Of the
      1007 patients initially identified, 668 (68 %) met the eligibility criteria. In
      univariate analysis, histologic grade and Ki67 were strongly associated with
      increased BMI, younger age, and African-American race, but less so with diabetes,
      hypertension, and hyperlipidemia. Multivariate analysis confirmed that higher
      histologic grade was associated with increased BMI (p = 0.02), and that increased
      Ki67 was associated with younger age (p = 0.0003) and African-American race (p =
      0.002). Additional analysis found that the association between increased BMI and
      higher-grade tumors was particularly significant in premenopausal women with ER
      positive disease. CONCLUSION: This study concludes that increased BMI is
      associated with aggressive-phenotype breast cancer and may be particularly
      relevant to ER-positive breast cancer developing in premenopausal African
      American women.

PMID- 24913912
TI  - Incomplete revascularization after coronary artery bypass graft operations is
      independently associated with worse long-term survival.
AB  - BACKGROUND: Complete revascularization (CR) has been suggested to provide
      benefits to both early and long-term outcomes, but the magnitude of the benefit
      and frequency of incomplete revascularization (IR) after coronary artery bypass
      graft operations is rarely explored and is the subject of the present study.
      METHODS: All patients who underwent isolated bypass operations (March 1995 to
      September 2007) at the Queen Elizabeth II Health Sciences Center (Halifax, NS,
      Canada) were identified. Revascularization was considered complete if each
      significantly diseased territory received at least 1 graft. Clinical
      characteristics of the CR and IR groups were examined to determine barriers of
      CR. A nonparsimonious Cox proportion model and survival curves were constructed
      to examine the association of CR and death after adjusting for clinically
      relevant covariates. RESULTS: A total of 8,570 patients underwent isolated
      nonredo bypass operations. IR, based on our strict definition, occurred in 19% of
      the patients. The territories most commonly affected were the right coronary and
      circumflex coronary territories. After adjustment for relevant clinical
      differences, IR was a significant independent predictor of long-term mortality
      (hazard ratio, 1.2; 95% confidence interval, 1.1 to 1.3). IR was also a
      significant independent predictor of hospital readmission for cardiac reasons
      after discharge (hazard ratio, 1.2; 95% confidence interval, 1.0 to 1.3).
      CONCLUSIONS: Despite advances in surgical revascularization, IR can occur in up
      to 19% of patients. IR significantly affects long-term death and readmission to
      hospital for cardiac reasons, and avoiding IR should therefore be a priority for
      surgeons during preoperative planning.

PMID- 24913911
TI  - Relationship between impaired adipogenesis of retroperitoneal adipose tissue and
      hypertrophic obesity: role of endogenous glucocorticoid excess.
AB  - Although the pro-adipogenic effect of glucocorticoid (GC) on adipose tissue (AT)
      precursor cell differentiation is openly accepted, the effect of chronically high
      peripheral levels of GC on AT mass expansion is not fully understood. In the
      present study, we aim to assess the in vitro adipogenic capacity of AT precursor
      cells isolated from retroperitoneal (RP) AT pads of the hypercorticosteronaemic,
      adult neonatally treated monosodium L-glutamate (MSG) male rat. To ascertain this
      issue, we explored the in vitro adipogenic process of stromal-vascular fraction
      (SVF) cells isolated from RPAT pads of 60-day-old MSG rats. The data recorded
      indicated that RPAT-SVF cells from hypercorticosteronaemic MSG rats, although
      displaying an enhanced proliferation capacity, differentiated slower than normal
      cells. This dysfunction was associated with a reduction in key parameters
      indicative of precursor cell commitment, differentiation capacity and the
      percentage of fully differentiated adipocytes, with a retarded maturation
      process. The distorted adipogenic capacity was highly conditioned by RPAT-SVF
      cells displaying a low committed population and both excessive and reduced
      expression of anti- (Pref-1 and Wnt-10b) and pro-adipogenic (mineralocorticoid
      receptor) signals respectively. Notably, the normalization of peripheral
      corticosterone levels in MSG rats, as a result of bilateral adrenalectomy
      combined with GC replacement therapy, fully prevented reduced RPAT precursor cell
      commitment and overall impaired adipogenesis. Our study strongly supports that
      the impaired adipogenic process observed in the adult hypertrophic obese MSG male
      rat is a GC-dependent mechanism, thus explaining the unhealthy RPAT expansion
      observed in human hypertrophic obese phenotypes, such as in the Cushing's
      syndrome. 

PMID- 24913914
TI  - A theoretical model to describe progressions and regressions for exercise
      rehabilitation.
AB  - This article aims to describe a new theoretical model to simplify and aid
      visualisation of the clinical reasoning process involved in progressing a single
      exercise. Exercise prescription is a core skill for physiotherapists but is an
      area that is lacking in theoretical models to assist clinicians when designing
      exercise programs to aid rehabilitation from injury. Historical models of
      periodization and motor learning theories lack any visual aids to assist
      clinicians. The concept of the proposed model is that new stimuli can be added or
      exchanged with other stimuli, either intrinsic or extrinsic to the participant,
      in order to gradually progress an exercise whilst remaining safe and effective.
      The proposed model maintains the core skills of physiotherapists by assisting
      clinical reasoning skills, exercise prescription and goal setting. It is not
      limited to any one pathology or rehabilitation setting and can adapted by any
      level of skilled clinician. 

PMID- 24913913
TI  - Quantifying the risk of incompatible kidney transplantation: a multicenter study.
AB  - Incompatible live donor kidney transplantation (ILDKT) offers a survival
      advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA).
      Program-specific reports (PSRs) fail to account for ILDKT, placing this practice
      at regulatory risk. We collected DSA data, categorized as positive Luminex,
      negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic
      crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304),
      from 22 centers. We tested associations between DSA, graft loss and mortality
      after adjusting for PSR model factors, using 9669 compatible patients as a
      comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard
      ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC
      (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft
      loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR =
      2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p <
      0.001) were associated with increased mortality. We simulated Centers for
      Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of
      being flagged. Compared to equal-quality centers performing no ILDKT, centers
      performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of
      being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72
      fold higher odds. Failure to account for ILDKT's increased risk places centers
      providing this life-saving treatment in jeopardy of regulatory intervention. 

PMID- 24913915
TI  - Inter-machine reliability of the Biodex and Cybex isokinetic dynamometers for
      knee flexor/extensor isometric, concentric and eccentric tests.
AB  - OBJECTIVES: To assess the inter-machine reliability of the Biodex System 3 Pro
      and Cybex Humac Norm Model 770 dynamometers for knee extensor and knee flexor
      peak torque measurements in isometric, concentric and eccentric tests. DESIGN:
      Randomized/crossover. SETTING: Exercise Research Laboratory, Federal University
      of Rio Grande do Sul (Brazil). PARTICIPANTS: 25 healthy male subjects. MAIN
      OUTCOME MEASURES: Isometric, concentric and eccentric knee extensor and knee
      flexor peak torques recorded in the same test procedure performed on both
      isokinetic dynamometers. One-way ANOVA, intraclass correlation coefficient (ICC),
      standard error of measurement (SEM) and coefficient of variation (CV) were used
      to verify significant differences, relative and absolute reliability between
      devices. RESULTS: No significant differences were found between tests performed
      on Biodex and Cybex (p > 0.05). ICC values indicated a high to very high
      reproducibility for isometric, concentric and eccentric peak torques (0.88-0.92),
      and moderate to high reliability for agonist-antagonist strength ratios (0.62
      0.73). Peak torque did not show great difference between dynamometers for SEM
      (3.72-11.27 Nm) and CV (5.27-7.77%). Strength ratios presented CV values of 8.57
      10.72%. CONCLUSION: Maximal knee extensor and knee flexor tests performed in
      isometric (60 degrees  of knee flexion), concentric and eccentric modes at 60
      degrees /s in Biodex and Cybex dynamometers present similar values.

PMID- 24913916
TI  - Overexpression of CupB5 activates alginate overproduction in Pseudomonas
      aeruginosa by a novel AlgW-dependent mechanism.
AB  - In Pseudomonas aeruginosa, alginate overproduction, also known as mucoidy, is
      negatively regulated by the transmembrane protein MucA, which sequesters the
      alternative sigma factor AlgU. MucA is degraded via a proteolysis pathway that
      frees AlgU from sequestration, activating alginate biosynthesis. Initiation of
      this pathway normally requires two signals: peptide sequences in unassembled
      outer-membrane proteins (OMPs) activate the AlgW protease, and unassembled
      lipopolysaccharides bind periplasmic MucB, releasing MucA and facilitating its
      proteolysis by activated AlgW. To search for novel alginate regulators, we
      screened a transposon library in the non-mucoid reference strain PAO1, and
      identified a mutant that confers mucoidy through overexpression of a protein
      encoded by the chaperone-usher pathway gene cupB5. CupB5-dependent mucoidy occurs
      through the AlgU pathway and can be reversed by overexpression of MucA or MucB.
      In the presence of activating OMP peptides, peptides corresponding to a region of
      CupB5 needed for mucoidy further stimulated AlgW cleavage of MucA in vitro.
      Moreover, the CupB5 peptide allowed OMP-activated AlgW cleavage of MucA in the
      presence of the MucB inhibitor. These results support a novel mechanism for
      conversion to mucoidy in which the proteolytic activity of AlgW and its ability
      to compete with MucB for MucA is mediated by independent peptide signals. 

PMID- 24913917
TI  - Purity assessment of recombinant human granulocyte colony-stimulating factor in
      finished drug product by capillary zone electrophoresis.
AB  - Current methods for determination of impurities with different charge-to-volume
      ratio are limited especially in terms of sensitivity and precision. The main goal
      of this research was to establish a quantitative method for determination of
      impurities with charges differing from that of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF, filgrastim) with superior precision and
      sensitivity compared to existing methods. A CZE method has been developed,
      optimized, and validated for a purity assessment of filgrastim in liquid
      pharmaceutical formulations. Optimal separation of filgrastim from the related
      impurities with different charges was achieved on a 50 MUm id fused-silica
      capillary of a total length of 80.5 cm. A BGE that contains 100 mM phosphoric
      acid adjusted to pH 7.0 with triethanolamine was used. The applied voltage was 20
      kV while the temperature was maintained at 25 degrees C. UV detection was set to
      200 nm. Method was validated in terms of selectivity/specificity, linearity,
      precision, LOD, LOQ, stability, and robustness. Linearity was observed in the
      concentration range of 6-600 MUg/mL and the LOQ was determined to be 0.3%
      relative to the concentration of filgrastim of 0.6 mg/mL. Other validation
      parameters were also found to be acceptable; thus the method was successfully
      applied for a quantitative purity assessment of filgrastim in a finished drug
      product.

PMID- 24913918
TI  - MicroRNA-581 promotes hepatitis B virus surface antigen expression by targeting
      Dicer and EDEM1.
AB  - Hepatitis B virus surface antigen (HBsAg) is an important risk factor for
      hepatocellular carcinoma (HCC) and is downregulated during hepatocarcinogenesis.
      MicroRNAs (miRNAs) are frequently deregulated in HCC tissues. However, whether
      the deregulation of certain miRNAs in HCC has an impact on HBsAg expression
      remains unclear. We found here that microRNA-581 (miR-581), which is deregulated
      during hepatocarcinogenesis, promoted HBsAg expression. Additionally, miR-581
      targeted Dicer and endoplasmic reticulum degradation-enhancing alpha-mannosidase
      like protein 1 (EDEM1) and repressed their expression. Although Dicer cannot
      process HBV transcripts, Dicer knockdown led to increased HBsAg secretion, most
      likely due to a reduction in the levels of Dicer-processed 7SL RNA fragments.
      Moreover, Dicer-processed 7SL RNA fragments partially inhibited the ability of
      miR-581 to stimulate HBsAg expression. Furthermore, we found that forced EDEM1
      expression inhibited miR-581-mediated induction of HBsAg. Finally, transfection
      of miR-581 into HepG2.2.15 cells promoted cell proliferation and led to
      upregulation of genes involved in development, cell proliferation and protein
      secretion. Altogether, we conclude that miR-581 promotes HBsAg expression by
      targeting Dicer and EDEM1. Our findings suggest that downregulation of miR-581
      during hepatocarcinogenesis may lead to a reduction in HBsAg expression and
      impede HCC development. 

PMID- 24913919
TI  - High-quality monolayer graphene synthesis on Pd foils via the suppression of
      multilayer growth at grain boundaries.
AB  - The segregation of carbon from metals in which carbon is highly soluble, such as
      Ni (~1.1 atom% at 1000  degrees C), is a typical method for graphene growth; this
      method differs from the surface-catalyzed growth of graphene that occurs on other
      metals such as Cu (<0.04 atom%). It has not been established whether strictly
      monolayer graphene could be synthesized through the traditional chemical vapor
      deposition route on metals where carbon is highly soluble, such as Pd (~3.5
      atom%). In this work, this issue is investigated by suppressing the grain
      boundary segregation using a pretreatment comprising the annealing of the Pd
      foils; this method was motivated by the fact that the typical thick growths at
      the grain boundaries revealed that the grain boundary functions as the main
      segregation channel in polycrystalline metals. To evaluate the high crystallinity
      of the as-grown graphene, detailed atomic-scale characterization with scanning
      tunneling microscopy is performed. 

PMID- 24913920
TI  - The doctor's role in helping dying patients with cancer achieve peace: a
      qualitative study.
AB  - BACKGROUND: Being at peace is important for the quality of life of dying cancer
      patients, but its features, and the role of the doctor in facilitating peace, are
      unclear. AIM: We sought to understand the features of a peaceful patient, and
      patients' preferences regarding the role of the doctor in facilitating a sense of
      peace. DESIGN: A grounded theory approach was used with semi-structured
      interviews. Patients were asked about the things that gave their life meaning and
      a sense of peace and how the doctor could support their spiritual well-being.
      Patients were also questioned about their concerns for their future.
      SETTING/PARTICIPANTS: In total, 15 cancer patients with advanced disease were
      interviewed in a variety of care settings. RESULTS: Patients were observed to be
      along a spectrum between having peace and not having peace. Features of the two
      extreme positions are described. Doctors could facilitate peace by developing a
      good relationship with cancer patients and supplying clear and honest information
      about what patients could expect as they approached their death. CONCLUSION:
      Spiritual well-being in cancer patients can be promoted by communication from
      doctors regarding prognosis, which allows them time to prepare for death, and
      recognition of their fears. However, acceptance of death does not always lead to
      the patient experiencing peace.

PMID- 24913921
TI  - A pilot study investigating the effect of a patient-held pain assessment tool in
      palliative care outpatients attending a rural Kenyan hospital.
AB  - BACKGROUND: Pain is a frequent and distressing symptom in palliative care
      patients worldwide. Careful assessment is the first vital step to relieve this
      suffering. Assessment tools form a useful adjunct to pain management, but whether
      they make a difference to the patient is not known. AIM: The objective of this
      study was to investigate whether the use of a patient-held pain assessment tool
      can make a difference in patient's pain control. SETTING AND PARTICIPANTS: AIC
      Kijabe Hospital, Kenya, has had a nurse-led Palliative Care Service since 2002,
      with an annual case-load of around 600 patients. Study participants were
      recruited from among adult palliative care patients attending the Outpatient
      Department. DESIGN: A quantitative experimental study methodology was employed.
      In the pre-intervention phase, pain was assessed at study entry and at 2 weeks,
      following 'standard' care at home; 49 patients were recruited for this phase. In
      the intervention phase, pain assessments were made at entry, with follow-up
      assessment after introduction to a patient-held pain assessment tool taken home
      by each patient; 50 patients were recruited for this phase. Analysis involved a
      comparison of baseline and 2-week pain scores between the two groups. RESULTS:
      The results demonstrated that the use of a patient-held pain assessment tool led
      to an increase in the number of patients reaching satisfactory pain relief, from
      30% in the pre-intervention group, to 69% in the intervention group. CONCLUSION:
      This study has demonstrated that a simple pain assessment tool, when linked to
      some action, may help achieve better analgesia.

PMID- 24913922
TI  - Sleep disturbances and resistant hypertension: association or causality?
AB  - Two main sleep disturbances, namely obstructive sleep apnea (OSA) and sleep
      deprivation, have gained growing interest in the field of hypertension research.
      This fact is supported not only by evidence that both disturbances are quite
      common in modern societies but also that OSA and sleep deprivation are associated
      with several pathways that may contribute to a predisposition to hypertension or
      even exacerbate blood pressure levels in hypertensive patients. In the present
      review, we will discuss current evidence supporting a potential role of these
      sleep disturbances in the resistant hypertension scenario. 

PMID- 24913923
TI  - Renal denervation after Symplicity HTN-3: an update.
AB  - After three years of excessive confidence, overoptimistic expectations and
      performance of 15 to 20,000 renal denervation procedures in Europe, the failure
      of a single well-designed US trial--Symplicity HTN-3--to meet its primary
      efficacy endpoint has cast doubt on renal denervation as a whole. The use of a
      sound methodology, including randomisation and blinded endpoint assessment was
      enough to see the typical 25-30 mmHg systolic blood pressure decrease observed
      after renal denervation melt down to less than 3 mmHg, the rest being likely
      explained by Hawthorne and placebo effects, attenuation of white coat effect,
      regression to the mean and other physician and patient-related biases. The modest
      blood pressure benefit directly assignable to renal denervation should be
      balanced with unresolved safety issues, such as potentially increased risk of
      renal artery stenosis after the procedure (more than ten cases reported up to
      now, most of them in 2014), unclear long-term impact on renal function and lack
      of morbidity-mortality data. Accordingly, there is no doubt that renal
      denervation is not ready for clinical use. Still, renal denervation is supported
      by a strong rationale and is occasionally followed by major blood pressure
      responses in at-risk patients who may otherwise have remained uncontrolled.
      Upcoming research programmes should focus on identification of those few patients
      with truly resistant hypertension who may derive a substantial benefit from the
      technique, within the context of well-designed randomised trials and independent
      registries. While electrical stimulation of baroreceptors and other
      interventional treatments of hypertension are already "knocking at the door", the
      premature and uncontrolled dissemination of renal denervation should remain an
      example of what should not be done, and trigger radical changes in evaluation
      processes of new devices by national and European health authorities.

PMID- 24913925
TI  - Perioperative Warming in Surgical Patients: A Comparison of Interventions.
AB  - The four arm study investigates how use of a preoperative forced-air warming
      blanket and adjustment of ambient surgical room temperature may contribute to
      prevention of perioperative hypothermia. Active warming interventions may prevent
      the drop in core temperature that occur as a result of surgical anesthesia. Core
      body temperatures from a convenience sample of 220 adult surgical patients were
      sequentially monitored in the preoperative, intraoperative, and post-anesthesia
      care units (PACU) while receiving: (a) routine surgical care, (b) application of
      preoperative forced-air warming blanket, (c) application of preoperative forced
      air warming blanket with adjustment of ambient surgical room temperatures, or (d)
      adjustment of ambient surgical room temperature only. Sample characteristics were
      evenly distributed among the four groups. There were no statistical differences
      in PACU core body temperatures. The application of forced-air warming blankets
      and room temperature adjustment interventions were not more effective than
      current practice in preventing perioperative hypothermia. 

PMID- 24913924
TI  - A phase II trial of BAY 43-9006 (sorafenib) (NSC-724772) in patients with
      relapsing and resistant multiple myeloma: SWOG S0434.
AB  - The authors assessed the overall response rate, including confirmed complete
      response (CR) and partial response, in patients with relapsed/refractory multiple
      myeloma treated with sorafenib. Qualitative and quantitative toxicities
      associated with this regimen were evaluated. Patients were eligible if they had a
      confirmed diagnosis of refractory or relapsed (RR) multiple myeloma (MM) with
      measurable monoclonal protein. Patients had to have adequate renal, hepatic,
      hematologic, and cardiac function with a Zubrod performance status of 0-2.
      Patients were given 400 mg sorafenib by mouth twice daily for 28-day treatment
      cycles. These patients were followed up for a maximum of 3 years to assess
      responses and adverse events. Twenty-three patients were enrolled. Of these, five
      were found to be ineligible for the following reasons: four had insufficient
      documentation of the baseline disease and one patient did not have measurable
      disease. All eighteen eligible patients were evaluable for toxicities. Three
      patients experienced grade 4 toxicities: one with thrombocytopenia, one with
      anemia, and one with renal failure. Four of the eighteen eligible patients were
      not assessable for response due to removal from protocol treatment prior to
      adequate disease assessment. Specifically, three were removed for either grade 4
      toxicity or progression of disease and one was removed per patient choice (due to
      reasons unrelated to treatment). Of the 18 patients who were assessed for
      toxicities, 5 (27.8%) received at least one fully dosed cycle, 2 (11.1%) of whom
      had all cycles fully dosed. No responses were observed on this study of the 14
      patients who were assessable for response. All patients have discontinued
      protocol treatment as of August 2008. Overall survival at 12 months was 50% (95%
      CI 27-73%) and median progression-free survival was 1.2 months (95% CI 1.0-5.4).
      The trial did not exhibit activity by the International Uniform Response Criteria
      for MM. Further research should focus on combination therapy of sorafenib with
      standard treatments in selected patients with RR MM. 

PMID- 24913926
TI  - Concept Analysis of Burden in Caregivers of Stroke Survivors During the Early
      Poststroke Period.
AB  - It is important to understand burden in caregivers of stroke survivors during the
      early poststroke period if we are to prevent or decrease the longer-term
      experience of caregiver burden and its consequences. This article reports a
      concept analysis of burden in caregivers of stroke survivors during the early
      poststroke period. A literature review using MEDLINE, PubMed, CINAHL, PsycINFO,
      and ISI Web of Knowledge databases (1960-2014) identified 32 relevant articles
      published from 1993 to 2013. Rodgers's evolutionary method of concept analysis
      was used. Three attributes--objective and subjective aspects, time spent caring
      for the stroke survivor, and uncertainty about the future for the stroke survivor
      and caregiver--were identified. Multiple definitions of caregiver burden have
      been used. In the early poststroke period, burden appears closely interconnected
      with other factors, some of which may be modifiable.

PMID- 24913927
TI  - Mother and offspring fitness in an insect with maternal care: phenotypic trade
      offs between egg number, egg mass and egg care.
AB  - BACKGROUND: Oviparous females have three main options to increase their
      reproductive success: investing into egg number, egg mass and/or egg care.
      Although allocating resources to either of these three components is known to
      shape offspring number and size, potential trade-offs among them may have key
      impacts on maternal and offspring fitness. Here, we tested the occurrence of
      phenotypic trade-offs between egg number, egg mass and maternal expenditure on
      egg care in the European earwig, Forficula auricularia, an insect with pre- and
      post-hatching forms of maternal care. In particular, we used a series of
      laboratory observations and experiments to investigate whether these three
      components non-additively influenced offspring weight and number at hatching, and
      whether they were associated with potential costs to females in terms of future
      reproduction. RESULTS: We found negative associations between egg number and mass
      as well as between egg number and maternal expenditure on egg care. However,
      these trade-offs could only be detected after statistically correcting for female
      weight at egg laying. Hatchling number was not determined by single or additive
      effects among the three life-history traits, but instead by pairwise interactions
      among them. In particular, offspring number was positively associated with the
      number of eggs only in clutches receiving high maternal care or consisting of
      heavy eggs, and negatively associated with mean egg mass in clutches receiving
      low care. In contrast, offspring weight was positively associated with egg mass
      only. Finally, maternal expenditure on egg care reduced their future
      reproduction, but this effect was only detected when mothers were experimentally
      isolated from their offspring at egg hatching. CONCLUSIONS: Overall, our study
      reveals simultaneous trade-offs between the number, mass and care of eggs. It
      also demonstrates that these factors interact in their impact on offspring
      production, and that maternal expenditure on egg care possibly shapes female
      future reproduction. These findings emphasize that studying reproductive success
      requires consideration of phenotypic trade-offs between egg-number, egg mass and
      egg care in oviparous species.

PMID- 24913928
TI  - Systematic review and meta-analysis of minimally invasive transforaminal lumbar
      interbody fusion rates performed without posterolateral fusion.
AB  - The need for posterolateral fusion (PLF) in addition to interbody fusion during
      minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) has yet to
      be established. Omitting a PLF significantly reduces overall surface area
      available for achieving a solid arthrodesis, however it decreases the soft tissue
      dissection and costs of additional bone graft. The authors sought to perform a
      meta-analysis to establish the fusion rate of MIS TLIF performed without
      attempting a PLF. We performed an extensive Medline and Ovid database search
      through December 2010 revealing 39 articles. Inclusion criteria necessitated that
      a one or two level TLIF procedure was performed through a paramedian MIS approach
      with bilateral posterior pedicle screw instrumentation and without posterolateral
      bone grafting. CT scan verified fusion rates were mandatory for inclusion. Seven
      studies (case series and case-controls) met inclusion criteria with a total of
      408 patients who underwent MIS TLIF as described above. The mean age was 50.7
      years and 56.6% of patients were female. A total of 78.9% of patients underwent
      single level TLIF. Average radiographic follow-up was 15.6 months. All patients
      had local autologous interbody bone grafting harvested from the pars
      interarticularis and facet joint of the approach side. Either
      polyetheretherketone (PEEK) or allograft interbody cages were used in all
      patients. Overall fusion rate, confirmed by bridging trabecular interbody bone on
      CT scan, was 94.7%. This meta-analysis suggests that MIS TLIF performed with
      interbody bone grafting alone has similar fusion rates to MIS or open TLIF
      performed with interbody supplemented with posterolateral bone grafting and
      fusion.

PMID- 24913929
TI  - Inadvertent subclavian artery cannulation treated by percutaneous closure.
AB  - Accidental arterial puncture occurs in around 1% and 2.7% of jugular and
      subclavian approaches, respectively. When a line has been inadvertently inserted
      into an artery at a noncompressible site, there is an increased risk for serious
      complications. This complication can be treated by either surgical or
      endovascular intervention or a combination; however, in critically ill patients
      or in those with impaired coagulation, therapeutic options are more limited. We
      describe successful endovascular management of inadvertent subclavian artery
      cannulation during insertion of a triple lumen central line catheter in a 35-year
      old man suffering from leukemia, with sepsis and multi-organ failure. He was
      hypotensive and hemodynamically unstable, with severe coagulopathy. The catheter
      had entered the artery at the level of the origin of the internal mammary artery,
      just above the origin of the vertebral artery. The tip was lying in the aortic
      arch. The artery was successfully closed by endovascular deployment of an 8
      French Angio-Seal device (St. Jude Medical, St. Paul, MN, USA). The device is
      licensed for use in femoral arterial puncture sites but provided safe and
      effective closure of the subclavian artery puncture in our patient. 

PMID- 24913930
TI  - Radiation induced malignant peripheral nerve sheath tumour of the second cervical
      nerve.
AB  - We report a 44-year-old with progressive quadriparesis due to a dumbbell
      malignant peripheral nerve sheath tumour (MPNST) of the second cervical nerve, 17
      years after whole brain radiotherapy for a pineal germinoma. To our knowledge
      this is the first case of radiation induced high cervical MPNST arising from a
      benign neurofibroma.

PMID- 24913931
TI  - Cognitive function, depression, anxiety and quality of life in Chinese patients
      with untreated unruptured intracranial aneurysms.
AB  - Detected unruptured intracranial aneurysms (UIA) are becoming more common with
      the increased utilization of CT angiography, MR angiography and digital
      subtraction angiography. A proportion of patients with UIA remain untreated. We
      investigated to assess cognitive function, depression, anxiety and quality of
      life (QoL) in Chinese patients with untreated UIA. Thirty one Chinese patients
      with untreated UIA and 25 healthy controls were identified and matched for
      variables including age, sex, and living area. Cognitive function was evaluated
      with the Montreal Cognitive Assessment (MoCA). Depression, anxiety and QoL were
      screened with the Self-Rating Depression Scale, Self-Rating Anxiety Scale, and
      Short Form-36, respectively. Non-parametric tests were used for comparisons
      between groups. No patient had cognitive dysfunction at 1 month or 1 year after
      detection of UIA. However, a significant decrease of overall MoCA subscores was
      found in 30 (97%) of 31 patients 5 years after UIA discovery, suggestive of mild
      cognitive impairment. A significant decrease in depression and anxiety was found
      in patients over time. QoL in patients was reduced most prominently in
      psychosocial function and social activities 1 year after detection of UIA, but
      these improved to within normal limits at the end of the follow-up period. For
      Chinese patients with untreated UIA, depression, anxiety and reduced QoL may be
      short-term complications. Mild cognitive impairment may be a long-term
      complication.

PMID- 24913932
TI  - Vertebrobasilar dissections: case series comparing patients with and without
      dissecting aneurysms.
AB  - Vertebrobasilar dissections are being increasingly diagnosed due to better
      awareness and increased availability of modern imaging techniques of the
      intracranial and extracranial arteries. The clinical presentation and outcome in
      patients with vertebrobasilar dissections may be complicated by dissecting
      aneurysms. The aim of this retrospective study was to compare the clinical
      profile of patients with vertebrobasilar dissections with and without dissecting
      aneurysms, and to determine predisposing factors to the development of aneurysms.
      Thirty patients (19 [63%] male; median age 44.5 years) were identified. The
      patients were divided into two groups, an aneurysmal dissection group with seven
      patients and a non-aneurysmal dissection group with 23 patients. Eight (27%)
      patients presented with dissection after trivial trauma, three (10%) following
      high-speed vehicular trauma, two (7%) were associated with infection, but most
      (57%) were apparently spontaneous. Migraine with aura (p=0.008) and female sex
      (p=0.03) were observed more frequently in the aneurysmal dissection group. Though
      vascular risk factors other than hypertension and atrial fibrillation were seen
      in a greater percentage of patients in the non-aneurysmal dissection group, this
      was not statistically significant. Patients were treated with antiplatelet agents
      (n=8) or warfarin (n=13) or underwent an endovascular intervention (n=6). Post
      discharge data were available in 19 patients, of whom 14 (74%) were independent
      at a median follow-up of 4 months. Female sex and migraine with aura may
      predispose to the formation of acute dissecting aneurysms and this requires
      further research. Larger, prospective studies are required to ascertain
      epidemiologic and etiologic factors predisposing patients to the development of
      both intracranial and extracranial dissecting aneurysms in the vertebrobasilar
      circulation.

PMID- 24913933
TI  - Role of serum TRAIL level and TRAIL apoptosis gene expression in multiple
      sclerosis and relation to brain atrophy.
AB  - One of the presumed pathological mechanisms of multiple sclerosis (MS) is the
      failure of apoptosis of autoreactive T lymphocytes. This study aimed to determine
      the relationship of the tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) mRNA gene expression ratio and serum TRAIL levels with MS and brain
      atrophy. This study was conducted on 53 relapsing-remitting Egyptian MS patients
      and 25 matched healthy volunteers. The expression of TRAIL in peripheral blood
      lymphocytes was analyzed by reverse transcription polymerase chain reaction,
      serum levels of soluble TRAIL (sTRAIL) were determined by enzyme-linked
      immunosorbent assay and brain MRI measured "black holes" and the bicaudate ratio
      as a measure of brain atrophy in all patients. The serum TRAIL level was lower in
      MS patients compared to controls but no difference was seen in the TRAIL mRNA
      gene expression ratio. No significant correlation was detected between the serum
      TRAIL level and the TRAIL mRNA expression ratio in either group. No statistically
      significant correlation was found between serum TRAIL levels or the TRAIL mRNA
      expression ratio with the number of black holes or the bicaudate ratio on MRI.
      Apoptosis of T lymphocytes is decreased in MS patients, which could be useful
      when designing treatments. There was no difference in the TRAIL mRNA gene
      expression ratio between MS patients and controls. 

PMID- 24913935
TI  - A vaginal Gartner duct cyst presenting as a cystocele during pregnancy.

PMID- 24913934
TI  - Mammographic, sonographic and MR imaging features of invasive micropapillary
      breast cancer.
AB  - PURPOSE: Describe mammographic, sonographic and MRI findings of invasive
      micropapillary carcinoma (IMPC) of the breast. MATERIALS AND METHODS: Review of
      the pathology database identified 43 patients (mean age, 59.3 years) with the
      diagnosis of breast IMPC. Three patients had no available imaging studies.
      Mammograms (40), breast ultrasounds (33) and MRIs (8) were retrospectively
      evaluated by two radiologists in consensus following the BI-RADS Lexicon.
      Clinical, histopathologic features, as well as hormone status were recorded.
      RESULTS: Twenty patients presented with palpable abnormality (20/40, 50%). Thirty
      five patients had an abnormal mammogram (87.5%, 35/40) showing 39 lesions, 29
      corresponding to masses (29/39, 74.4%), 11 associated with microcalcifications
      and two associated with architectural distortion. Sonography identified 41 masses
      (in 33 patients) displaying an irregular shape (30/41, 73.2%), appearing
      hypoechoic (39/41, 95%), with spiculated or angular margins (26/41, 63.4%), non
      parallel orientation (26/41, 63.4%) and combined acoustic posterior pattern
      (18/41, 44%). MRI identified 13 lesions (in eight patients), 12 as masses (12/13,
      92.3%) with irregular or spiculated margins (12/12, 100%), eight displaying an
      irregular or lobulated shape (8/12, 66.7%), six with homogeneous internal
      enhancement (6/12, 50%) and eight with type 3 enhancement curve (8/12, 61.5%).
      Associated non-mass like enhancement was noted in two patients. Twenty-nine
      patients had associated lymphovascular invasion (29/40, 72.5%) and axillary lymph
      node metastases were present in 22 of the 39 patients (22/39, 56%). CONCLUSION:
      Invasive ductal carcinoma with IMPC features display imaging findings highly
      suspicious of malignant lesions. They are associated with high lymphovascular
      invasion and lymph node metastases rates.

PMID- 24913936
TI  - Wernicke's encephalopathy complicating gestational hyperemesis.

PMID- 24913937
TI  - Effect of pulsed electromagnetic field therapy on prostate volume and vascularity
      in the treatment of benign prostatic hyperplasia: a pilot study in a canine
      model.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is a result of urogenital aging.
      Recent studies suggest that an age-related impairment of the blood supply to the
      lower urinary tract plays a role in the development of BPH and thus may be a
      contributing factor in the pathogenesis of BPH. The canine prostate is a model
      for understanding abnormal growth of the human prostate gland. We studied the
      efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify
      prostate blood flow and evaluated its effect on BPH. METHODS: PEMF (5 min, twice
      a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume,
      Doppler assessment by ultrasonography, libido, semen quality, testosterone
      levels, and seminal plasma volume, composition and pH were evaluated before and
      after treatment. RESULTS: The 3 weeks of PEMF produced a significant reduction in
      prostatic volume (average 57%) without any interference with semen quality,
      testosterone levels or libido. Doppler parameters showed a reduction of
      peripheral resistances and a progressive reduction throughout the trial of the
      systolic peak velocity, end-diastolic velocity, mean velocity, mean, and peak
      gradient of the blood flow in the dorsal branch of the prostatic artery. The
      pulsatility index and the resistance index did not vary significantly over time.
      CONCLUSIONS: The efficacy of PEMF on BPH in dogs, with no side effects, suggests
      the suitability of this treatment in humans and supports the hypothesis that
      impairment of blood supply to the lower urinary tract may be a causative factor
      in the development of BPH.

PMID- 24913938
TI  - Wettability, polarity, and water absorption of holm oak leaves: effect of leaf
      side and age.
AB  - Plant trichomes play important protective functions and may have a major
      influence on leaf surface wettability. With the aim of gaining insight into
      trichome structure, composition, and function in relation to water-plant surface
      interactions, we analyzed the adaxial and abaxial leaf surface of holm oak
      (Quercus ilex) as a model. By measuring the leaf water potential 24 h after the
      deposition of water drops onto abaxial and adaxial surfaces, evidence for water
      penetration through the upper leaf side was gained in young and mature leaves.
      The structure and chemical composition of the abaxial (always present) and
      adaxial (occurring only in young leaves) trichomes were analyzed by various
      microscopic and analytical procedures. The adaxial surfaces were wettable and had
      a high degree of water drop adhesion in contrast to the highly unwettable and
      water-repellent abaxial holm oak leaf sides. The surface free energy and
      solubility parameter decreased with leaf age, with higher values determined for
      the adaxial sides. All holm oak leaf trichomes were covered with a cuticle. The
      abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43%
      polysaccharides. For the adaxial side, it is concluded that trichomes and the
      scars after trichome shedding contribute to water uptake, while the abaxial leaf
      side is highly hydrophobic due to its high degree of pubescence and different
      trichome structure, composition, and density. Results are interpreted in terms of
      water-plant surface interactions, plant surface physical chemistry, and plant
      ecophysiology. 

PMID- 24913939
TI  - Genetic counseling and prenatal diagnosis for hereditary hearing loss in high
      risk families.
AB  - OBJECTIVE: Genetic counseling and prenatal diagnosis are very necessary and
      accurate to detect hereditary hearing loss, especially in high-risk families.
      Prenatal diagnosis is testing for diseases or conditions in fetuses before born,
      which gives parents the chance to prepare psychologically, financially and
      medically for the probable health and educational needs of the affected neonates.
      METHODS: 54 unrelated families with children affected with non-syndromic
      sensorineural hearing loss were enrolled in the study and received genetic
      analysis with microarray and DNA sequencing technologies. Genetic counseling was
      provided to each participating families, and prenatal diagnosis was given to
      those at risk and would like to know their fetuses' genotypes and probable
      hearing statuses. RESULTS: Half the cases in the present study were diagnosed
      with confirmed pathogenic mutations and clear inheritance patterns. After
      receiving genetic counseling, 24 carrier couples with pathogenic mutations chose
      to proceed prenatal diagnosis, the results of which were in accordance with the
      pregnancy outcomes. Infants prenatally detected to be monoallelic mutation
      carriers and those harbored neither deafness-causing mutations form their parents
      passed newborn hearing screening and six-month follow-ups, while neonates
      prenatally detected to be carriers of diallelic or compound heterozygous
      mutations developed hearing loss after birth. CONCLUSIONS: With appropriate
      genetic counseling and support services provided, the genetic testing and the
      prenatal diagnosis of hearing loss were valued by carrier couples for the
      information provided for future family planning and probably the preparation for
      the health and educational needs of the affected neonates.

PMID- 24913941
TI  - Social mobility in the context of fathering: the intergenerational link in
      parenting among co-resident fathers.
AB  - Intergenerational transmissions extend across a number of family-related
      behaviors, including marriage timing, fertility, and divorce. Surprisingly, few
      studies investigate the link between the fathering men experience and the
      fathering they ultimately engage in. I use data on the grandfathers and fathers
      of the 2001 U.S. birth cohort - measured in the Early Childhood Longitudinal
      Study (N=4050) - to test whether men's perception of the parenting they received
      influences their subsequent paternal self-assessments and behaviors. I find a
      nonlinear association between experiencing warm fathering and men's self-assessed
      parenting quality and stress. Men with particularly warm fathers are more likely
      to report being good fathers themselves. Those who report having the harshest
      fathers also exhibit better paternal self-perceptions and lower stress.
      Perceptions of paternal warmth show similar associations with men's fathering
      engagement. This research sheds light on the significance of family dynamics and
      how a legacy of fathering may contribute to inequality. 

PMID- 24913940
TI  - Identification and characterization of novel inhibitors of Mammalian aspartyl
      aminopeptidase.
AB  - Aspartyl aminopeptidase (DNPEP) has been implicated in the control of angiotensin
      signaling and endosome trafficking, but its precise biologic roles remain
      incompletely defined. We performed a high-throughput screen of ~25,000 small
      molecules to identify inhibitors of DNPEP for use as tools to study its biologic
      functions. Twenty-three confirmed hits inhibited DNPEP-catalyzed hydrolysis of
      angiotensin II with micromolar potency. A counter screen against glutamyl
      aminopeptidase (ENPEP), an enzyme with substrate specificity similar to that of
      DNPEP, identified eight DNPEP-selective inhibitors. Structure-activity
      relationships and modeling studies revealed structural features common to the
      identified inhibitors, including a metal-chelating group and a charged or polar
      moiety that could interact with portions of the enzyme active site. The compounds
      identified in this study should be valuable tools for elucidating DNPEP
      physiology. 

PMID- 24913942
TI  - Factors associated with positive relationships between stepfathers and adolescent
      stepchildren.
AB  - This study employs nationally representative data on adolescents and their
      stepfathers (n=2085) from the National Longitudinal Study of Adolescent Health
      (Add Health) to examine factors associated with positive stepfather-stepchild
      relationships in married stepfamilies. Results reveal substantial variability in
      the perceived quality of adolescents' relationships with stepfathers. Structural
      equation models using Wave I data reveal that close relationships with mothers
      and close ties between mothers and stepfathers are positively related to the
      perceived quality of adolescents' relationships with stepfathers. Longitudinal
      models using Waves I and II do not yield definitive results but suggest that the
      direction of influence runs in both directions, with the mother-child
      relationship and the stepfather-stepchild relationship mutually reinforcing one
      another. We identify a number of other factors that are associated with positive
      stepfather-stepchild ties, as well as a few factors that may be less
      consequential than previously thought. Most of the correlates of positive
      stepfather-stepchild relationships are similar for boys and girls; for Whites,
      Blacks, and Hispanics; and for stepfamilies of various durations. 

PMID- 24913943
TI  - The temporal variation of ethnic segregation in a city: evidence from a mobile
      phone use dataset.
AB  - The aim of this study is to determine the temporal variation of ethnic
      segregation in the city of Tallinn, the capital of Estonia. We employ data on
      mobile-phone use to compare variations in segregation indices during the day, the
      week, and the year. The results indicate that the locations of people are more
      segregated at night, with considerably less segregation during the daytime. The
      segregation is significantly lower on workdays compared to weekends. Segregation
      is also lower during summer holidays compared to the winter working period. The
      results show that although places of residence are segregated, different ethnic
      groups use the city together during the day, which increases the potential for
      interethnic contacts. The results demonstrate also that temporal segregation
      indices based on mobile-phone use are considerably lower than segregation indices
      of places of residence that are derived from the census. 

PMID- 24913944
TI  - Correlates of experiences and perceptions of anti-Semitism among Jews in the
      United States.
AB  - This paper investigates American Jews' personal experiencing of anti-Semitism and
      perception of its extent. Analysis of NJPS-2000/2001 indicates that lower age,
      less education, and American nativity increase experiencing of anti-Semitism.
      Religious identification and attachment to Israel are positively associated with
      anti-Semitic experience; friendship with other Jews has the opposite effect.
      Contextual factors are not significant for the experiencing of anti-Semitism but
      living in a state that leans toward the Democratic Party has a downward effect.
      Contrary to experience, younger age and higher education are negatively
      associated with the perception of a high incidence of anti-Semitism. Being a
      woman, American born, and living in states with high concentrations of Jews
      positively affect Jews' perception of anti-Semitism. A paramount determinant of
      the perception of anti-Semitism is the individual's belief that he or she has
      experienced it. The results are discussed in reference to three working
      hypotheses of integration, group identification, and environment. 

PMID- 24913945
TI  - Undocumented migration and the residential segregation of Mexicans in new
      destinations.
AB  - This study uses data from the 2000 Census and 2005-2009 American Community Survey
      to examine the impact of undocumented Mexican migration to new destinations on
      residential segregation between Mexican immigrants and native-born whites and
      native-born blacks. We find that Mexican-white and Mexican-black segregation is
      higher in new Mexican gateways than in established areas and that, for Mexican
      immigrant segregation from whites, this heightened level of residential
      segregation in new destinations can be explained by the high presence of
      unauthorized Mexican immigrants living there which tends to bolster segregation
      between the two groups. By contrast, Mexican-immigrant segregation from native
      born blacks tends to be lower in areas with larger undocumented populations, a
      pattern that is especially true in new destinations. Neither of these opposing
      effects of legal status on Mexican-immigrant segregation can be explained by
      compositional differences in assimilation (English ability and earnings) between
      documented and undocumented immigrants nor by structural variation in
      metropolitan areas, suggesting a unique association between legal status and
      segregation. 

PMID- 24913946
TI  - Bring a gun to a gunfight: armed adversaries and violence across nations.
AB  - We use homicide data and the International Crime Victimization Survey to examine
      the role of firearms in explaining cross-national variation in violence. We
      suggest that while gun violence begets gun violence, it inhibits the tendency to
      engage in violence without guns. We attribute the patterns to adversary effects
      i.e., the tendency of offenders to take into account the threat posed by their
      adversaries. Multi-level analyses of victimization data support the hypothesis
      that living in countries with high rates of gun violence lowers an individual's
      risk of an unarmed assault and assaults with less lethal weapons. Analyses of
      aggregate data show that homicide rates and gun violence rates load on a separate
      underlying factor than other types of violence. The results suggest that a
      country's homicide rate reflects, to a large extent, the tendency of its
      offenders to use firearms. 

PMID- 24913947
TI  - Ethnic diversity, trust, and the mediating role of positive and negative
      interethnic contact: a priming experiment.
AB  - This study not only shows that the empirically well-established negative
      relationship between residential diversity and trust in neighbors holds for the
      case of Germany, but goes beyond existing research by providing experimental
      evidence on the causal nature of the diversity effect. Respondents exposed to
      experimental stimuli that made salient the ethnic or religious heterogeneity of
      their neighborhoods display significantly lower levels of trust in their
      neighbors than do respondents in the control group. Further, we explore the role
      of interethnic contact in mediating the relationship between diversity and trust
      in a degree of detail unmatched by earlier studies. We consider not only positive
      forms of interethnic contact such as friendships, but also neutral and negative
      encounters between people of native and immigrant origin. We find that
      interethnic contacts mediate negative diversity effects on trust in different
      ways for both groups. For natives, distant encounters and negative experiences
      with immigrants in diverse contexts reduce trust, whereas for people of immigrant
      origin trust in neighbors suffers from the relatively small number of native
      acquaintances in diverse neighborhoods. 

PMID- 24913948
TI  - Subjective time pressure: general or domain specific?
AB  - Chronic time pressure has been identified as a pervasive societal problem,
      exacerbated by high demands of the labor market and the home. Yet time pressure
      has not been disaggregated and examined separately across home and work contexts,
      leaving many unanswered questions regarding the sources and potentially stressful
      consequences of time pressure. Using data collected in the United States General
      Social Survey waves 2002 and 2004, this study disaggregates time pressure into
      the domains of home and work, and asks whether considering time pressures within
      distinct work and home contexts reveals distinct predictors or associations with
      stress. Findings show that both predictors and stress associations differ across
      work and home pressures, revealing both methodological and theoretical
      implications for the study of time pressure and work and family life more
      generally. 

PMID- 24913949
TI  - Foreign direct investment, development, and overshoot.
AB  - Overshoot of the earth's carrying capacity is an acute concern for sustainability
      initiatives that seek to equalize access to the natural resources that are
      requisite to meet the basic needs of humanity. Demands on nature that exceed
      ecological capacities compromise critical ecosystem functions that provision the
      inputs necessary for life. This paper draws on concepts and analytical frameworks
      from the natural, physical, and social sciences to assess the drivers of
      sustainability at the global and national level. Integrative theoretical
      predictions are tested in a structural equation model that advances empirical
      research on overshoot and outflows of foreign investments that is relatively
      lacking in the literature. Findings highlight the differential impacts of key
      aspects of economic globalization on both development and overshoot across
      nations. 

PMID- 24913950
TI  - Cohabitation, post-conception unions, and the rise in nonmarital fertility.
AB  - The majority of U.S. nonmarital births today are to cohabiting couples. This
      study focuses on transitions to cohabitation or marriage among pregnant unmarried
      women during the period between conception and birth. Results using the newly
      released 2006-2010 National Survey of Family Growth show that nonmarital
      pregnancy is a significant precursor to cohabitation before childbirth (18%),
      exceeding transitions to marriage (5%) by factor of over three. For pregnant
      women, the boundaries between singlehood, cohabitation, and marriage are highly
      fluid. The results also reveal substantial variation in post-conception
      cohabiting and marital unions; e.g., disproportionately low percentages of black
      single and cohabiting women transitioned into marriage, even when conventional
      social and economic risk factors are controlled. The multivariate analyses also
      point to persistent class differences in patterns of family formation, including
      patterns of cohabitation and marriage following conception. Poorly educated
      women, in particular, are much more likely to become pregnant as singles living
      alone or as partners in cohabiting unions. But compared with college-educated
      women, pregnancies are less likely to lead to either cohabitation or marriage.
      This paper highlights the conceptual and technical challenges involved in making
      unambiguous interpretations of nonmarital fertility during a period of rising
      nonmarital cohabitation. 

PMID- 24913952
TI  - Place matters: the impact of place of residency on racial attitudes among
      regional and urban migrants.
AB  - Scholars have debated whether racial attitudes are socialized early in life and
      persist throughout one's lifetime or are open to influences from one's
      environment as an adult. This study introduces another approach that holds that
      place, as opposed to the timing of socialization, is an important consideration
      for the socialization of racial attitudes. Using data from the American National
      Election Study, we consider the effect of region and urban residency on racial
      attitudes by comparing lifelong residents of these locations to those who migrate
      into and out of them. Using improved measures of early life socialization and
      region of residency, we conclude that a place-based model can be used to explain
      the socialization of racial resentment. For regional migrants, those moving into
      and out of the non-South maintain levels of racial resentment similar to non
      Southern stayers. For urban migrants, the lifelong openness model of
      socialization was most appropriate. These migrants were more likely to change and
      adopt the level of racial resentment similar to that of their destination peers.
      These findings generally persist across time. 

PMID- 24913951
TI  - Parvenus and conflict in elite cohorts.
AB  - Previous studies find that greater workplace diversity leads to higher degrees of
      conflict in low and medium-status workgroups. This paper examines whether similar
      dynamics operate in elite cohorts. We use data from a survey of White House
      Fellows (N=475) to look at how the presence of parvenus-individuals from
      underrepresented groups in elite environments-change the rate at which fellows
      reported conflict with each other and with the director of the program. We find
      that there is no unified "parvenu experience." Analysis of the interaction
      between race and cohort diversity reveals inflection points consistent with
      Kanter's (1977) theory of tokenism, but the effects of increasing diversity
      diverge: for Hispanics, conflict with the director increases with diversity,
      while for Asians, conflict falls with diversity. While other groups' level of
      conflict with their peers stays roughly constant, Asians' reported level of
      conflict with their peers increases with diversity. 

PMID- 24913953
TI  - Are racist attitudes related to experiences of racial discrimination? Within
      sample testing utilising nationally representative survey data.
AB  - Although the relationship between an individual's racist attitudes and
      discriminatory behaviours has been widely studied, the association between racist
      attitudes among perpetrators and experiences of racism among targets has been
      under-examined. Based on data from the 2001-8 Australian Challenging Racism
      Project survey, this paper details a novel method to investigate the link between
      racist attitudes and experiences of discrimination utilising two separate models
      linked by nomination of cultural or ethnic groups who do not fit into Australian
      society (i.e., out-groups). Those identified as out-groups were more likely to
      report experiences of discrimination than those who were not nominated as out
      groups. Overall, out-group nomination by those with racist attitudes strongly
      predict experiences of discrimination among these same target out-groups, OR=2.2,
      F(6, 12,348)=78.61, p<.001. Racist attitudes are related to racist behaviours
      among perpetrators that are, in turn, related to experiences of racial
      discrimination among targets. This study demonstrates that attitudes not only
      affect majority group behaviour but also drive the resulting experiences of
      discrimination for minority group members. 

PMID- 24913954
TI  - Time with children and employed parents' emotional well-being.
AB  - Using the experience sampling method and survey data from the 500 Family Study
      this study examined how parents feel when they spend time with their children and
      whether their emotional experiences differ by type of activity and the parent's
      gender. I found that mothers spent more time in childcare than fathers but this
      disparity was primarily due to mothers' more frequent engagement in activities
      that were not child-centered (i.e., non-focused and passive childcare).
      Multilevel models further showed that engagement in these activities was related
      to higher positive affect. Shared meals and leisure activities were particularly
      beneficial to parents' emotional well-being and the likelihood of engaging in
      them was not affected by parents' paid work hours. By contrast, routine childcare
      was associated with increased stress and lower engagement but only among mothers.
      Mothers were also less likely to provide childcare in conjunction with their
      spouse. These findings reveal the subtle dimensions of the unequal division of
      childcare by gender. 

PMID- 24913955
TI  - How to explant a diseased liver for living donor liver transplantation after
      previous gastrectomy with severe adhesion (with video).
AB  - We performed living donor liver transplantation (LDLT) in a patient who had
      undergone distal gastrectomy for gastric ulcer disease with Billroth I
      reconstruction 30 years before the LDLT. The adhesion was very severe between
      remnant stomach and hepatic hilum as well as left liver lobe with shortening of
      hepatoduodenal structures. After dissection of the infrahepatic inferior vena
      cava, the Spiegel lobe was identified from the dorsal side. The Spiegel lobe was
      then penetrated with a right angle dissector so that a plastic tape could be
      placed around the whole adhesion, including important structures in the
      hepatoduodenal ligament. Next, the right hepatic vein was transected with a
      vascular stapler using Pringle's maneuver using the plastic tape to fasten the
      entire adhesional structure. Subsequently, the trunk of the middle and left
      hepatic vein was transected after clamping. The remaining short hepatic veins in
      the left side were divided completely from the cranial to the caudal direction to
      dissect Spiegel's lobe. Finally, the hepatoduodenal ligament was identified from
      the attached remnant stomach and the duodenum and a vascular clamp was placed on
      the entire hepatoduaodenal ligament. Finally, the diseased liver was explanted
      for graft implantation. Thus, retrograde explantation of the liver was effective
      in decreasing the risk of damaging vital elements in the hepatoduodenal ligament,
      the remnant stomach, and the duodenum. 

PMID- 24913956
TI  - Shoulder function following reconstruction with the supraclavicular artery island
      flap.
AB  - OBJECTIVES/HYPOTHESIS: The supraclavicular artery island flap (SCAIF) is a
      pedicled fasciocutaneous flap used for head and neck reconstruction. In recent
      years, its use has significantly increased as a result of several advantageous
      characteristics, including pliability, an excellent color and texture match,
      ability to reconstruct a variety of skin and aerodigestive tract defects, and
      short harvest times. Clinical experience suggests that donor site complications
      are relatively infrequent and typically self-limiting, and there have been no
      documented cases of prolonged or permanent shoulder dysfunction. However, formal
      studies have not been performed to assess this outcome. The goal of this study
      was to evaluate the effects of SCAIF flap harvest on postoperative shoulder
      strength and flexibility. STUDY DESIGN: Prospective cohort pilot study. METHODS:
      Data was gathered prospectively during routine follow-up and surveillance. The
      Penn Shoulder Score and Constant Shoulder Scale were used to measure subjective
      and objective outcomes. Physical therapists performed testing for strength and
      flexibility. RESULTS: Ten patients were evaluated from January to July, 2013.
      Subjective self-reporting of shoulder function and satisfaction was good to
      excellent in most patients. The majority of patients demonstrated limitations in
      range of motion for one or more shoulder movements. Muscle strength was preserved
      postoperatively. CONCLUSION: Harvest of the SCAIF appears to have limited
      postoperative morbidity. Postoperative shoulder strength and function appears to
      be very good; however, some limitation of range of motion was observed. LEVEL OF
      EVIDENCE: 4

PMID- 24913957
TI  - Two-dimensional oxides and their role in electron transfer mechanisms with
      adsorbed species.
AB  - Insulating or semiconducting oxides prepared in the form of ultrathin films grown
      on a metal may exhibit phenomena and behaviors that make them quite interesting
      for their potential applications in catalysis and other fields. In this review we
      consider in particular what is probably the most relevant one of these phenomena,
      i.e., the possibility to decouple the wave functions of the metal support and the
      adsorbed species by means of the thin separating dielectric layer, and
      consequently to induce charge transfer in one or the other direction, producing
      collections of positively or negatively charged adsorbates. We describe the basic
      results that opened up this relatively new field and discuss formation of
      negatively and positively charged atomic adsorbates and the mechanisms at the
      basis of the electron flow through the thin dielectric layer. We illustrate some
      direct consequences of the charge transfer on two-dimensional oxide layers, like
      the possibility to change the shape of supported clusters, or to dissociate
      chemical bonds with mechanisms that are different from the respective bulk
      oxides. We also discuss how the properties of ultrathin films, and in particular
      the work function of the system, can be modified by selective interstitial or
      substitutional doping. 

PMID- 24913958
TI  - In vivo MRI for effective non-invasive detection and follow-up of an orthotopic
      mouse model of lung cancer.
AB  - One of the main reasons for the dismal prognosis of lung cancer is related to the
      late diagnosis of this pathology. In this study, we evaluated the potential of
      optimized lung MRI techniques as a completely non-invasive approach for non-small
      cell lung cancer (NSCLC) MRI in vivo detection and follow-up in a mouse model of
      lung adenocarcinoma expressing the luciferase gene. Bioluminescent lung tumour
      cells were orthotopically implanted in immuno-deficient mice. Ultra-short echo
      time (UTE) MRI free-breathing acquisitions were compared with standard gradient
      echo lung MRI (FLASH) using both respiratory-gated and free-breathing protocols.
      The MRI findings were validated against bioluminescence imaging (BLI) and gold
      standard histopathology analysis. Adenocarcinoma-like pathological tissue was
      successfully identified in all the mice with gated-FLASH and non-gated UTE MRI,
      and good tumour co-localization was found between MRI, BLI and histological
      analyses. An excellent or good correlation was found between the measured
      bioluminescent signal and the total tumour volumes quantified with UTE MRI or
      gated-FLASH MRI, respectively. No significant correlation was found when the
      tumours were segmented on non-gated MR FLASH images. MRI was shown to be a
      powerful imaging tool able to detect, quantify and longitudinally monitor the
      development of sub-millimetric NSCLCs. To our knowledge, this is the first study
      which proves the feasibility of a completely non-invasive MRI quantitative
      detection of lung adenocarcinoma in freely breathing mice. The absence of
      ionizing radiation and the high-resolution of MRI, along with the complete non
      invasiveness and good reproducibility of the proposed non-gated protocol, make
      this imaging tool ideal for direct translational applications.

PMID- 24913959
TI  - Mapping quantitative trait loci affecting some carcass and meat traits in duck
      (Anas platyrhynchos).
AB  - Contrary to chicken and livestock mammals, duck genome has not been explored
      much. Nowadays a relatively small number of reports on molecular variability and
      mapping of loci in Peking ducks has been published. Therefore, the objective of
      this study was to detect single loci affecting body weight, carcass and meat
      traits in Peking ducks (Anas platyrhynchos). The study was based on an F2 cross
      between two parental lines A-55 and GL-30. Phenotypes of 387 birds from
      generation F2 including carcass and meat quality traits were collected. Linkage
      map, of the linkage group CAU1, consisting of 29 microsatellite markers was
      constructed. One highly significant (p < 0.01) QTL for skin weight was identified
      at the beginning (0 cM) of the linkage group CAU1. Two significant QTL (p < 0.05)
      were found for fatness of leg muscle and leg muscle electrical conductivity - 24
      hours post slaughtering (EC24h) at 178 and 100 cM, respectively. Additionally one
      suggestive QTL for odour of leg muscle was identified at 265 cM.

PMID- 24913960
TI  - To our mentor and friend, professor Sole-Balcells.

PMID- 24913961
TI  - Trans-umbilical single-port radical nephrectomy with concomitant cholecystectomy.
AB  - OBJECTIVES: Occasionally, the development of laparoscopic procedures allows the
      performance of combined surgeries. Currently, some of these can be carried out by
      trans-umbilical single-port laparoscopy. MATERIAL AND METHODS: We report a
      patient with renal tumor of 4.5cm and cholelithiasis who undergone to trans
      umbilical single port-right radical nephrectomy with concomitant cholecystectomy.
      This is the first case reported in Spain that this combined procedure is
      performed using umbilical single port surgery. RESULTS: No complications (intra
      or postoperative) have been described in this case, achieving proper control of
      tumor pathology and an excellent cosmetic outcome. CONCLUSION: In those cases in
      which multidisciplinary approach is required, surgery can be performed by trans
      umbilical single-port laparoscopy as consequence of its reduced postoperative
      morbidity and better cosmetic results.

PMID- 24913962
TI  - Concomitant systemic lupus erythematosus and HIV: case series and literature
      review.
AB  - OBJECTIVES: To determine the effect of systemic lupus erythematosus (SLE) and
      human immunodeficiency virus (HIV) infection on the course of each other and to
      review the published reports on concomitant SLE and HIV infection. METHODS: We
      performed a retrospective review of the records of patients with SLE and HIV seen
      in the Department of Rheumatology at the Inkosi Albert Luthuli Central Hospital,
      Durban, South Africa. We used the terms "systemic lupus erythematosus" and "HIV"
      or "AIDS" to identify patients with SLE and HIV infection reported in the English
      medical literature. RESULTS: We identified 13 patients with SLE and HIV
      infection. All the patients were females and there were 11 African blacks and 2
      Indians. SLE and HIV infection were diagnosed together in 6 patients. In this
      group, there were 5 lupus flares in 4 patients, and 2 of the flares followed
      highly active anti-retroviral treatment (HAART). Five patients developed HIV
      after the diagnosis of SLE. The 3 patients in whom follow-up data was available
      had inactive SLE, one of whom was on HAART. Two HIV-positive patients developed
      SLE after receiving HAART for 30 and 35 mo. Seven of our patients also had
      tuberculosis. Our literature search identified 58 previously reported patients
      with HIV and SLE. CONCLUSION: Our case series and review of the literature show
      that there is a reduction in SLE disease activity in patients with concomitant
      SLE and HIV. However, when lupus flares occur in HIV-positive patients, they are
      unrelated to the use of HAART.

PMID- 24913963
TI  - Simulation in spinal diseases.
AB  - Simulation is frequent in spinal disease, resulting in problems for specialists
      like Orthopedic Surgeons, Neurosurgeons, Reumathologists, etc. Simulation
      requires demonstration of the intentional production of false or exaggerated
      symptoms following an external incentive. The clinician has difficulties in
      demonstrating these criteria, resulting in misdiagnosis of simulation or
      misinterpretation of the normal patient as a simulator, with the possibility of
      iatrogenic distress and litigation. We review simulation-related problems in
      spine, proposing a terminological, as well as a diagnostic strategy including
      clinical and complementary diagnosis, as a way to avoid misinterpretation and
      minimize the iatrogenic distress and liability Based on the clinical-Forensic
      author's expertise, the literature is analyzed and the terminology readdressed to
      develop new terms (inconsistences, incongruences, discrepancies and
      contradictions). Clinical semiology and complementary test are adapted to the new
      scenario. Diagnostic strategy relies on anamnesis, clinical and complementary
      tests, adapting them to a uniform terminology with clear meaning of signs and
      symptoms. 

PMID- 24913964
TI  - Myelitis transverse in Sjogren's syndrome and systemic lupus erythematosus:
      presentation of 3 cases.
AB  - Transverse myelitis is a rare focal inflammation of the spinal cord. Multiple
      etiologies have been identified including autoimmune diseases, mainly systemic
      lupus erythematosus and Sjogren' syndrome. It can occur in an acute or subacute
      clinical onset, with the acute presentation having a worse prognosis. An early
      diagnosis and intensive treatment are important features recommended in these
      patients. We present three cases with transverse myelitis associated with
      autoimmune diseases. We discuss different clinical manifestations, association
      with autoantobodies, radiologic findings, and therapeutic and prognostic issues.

PMID- 24913965
TI  - Antineutrophil cytoplasm antibody: positivity and clinical correlation.
AB  - OBJECTIVE: To determine positivity and clinical correlation of anti-neutrophil
      cytoplasmic antibodies (ANCA), taking into account the interference of
      antinuclear antibodies (ANA). MATERIAL AND METHODS: A prospective study was
      conducted in the Laboratory of Immunology of the National Cuban Center of Medical
      Genetic during one year. Two hounded sixty-seven patients with indication for
      ANCA determination were included. ANCA and ANA determinations with different cut
      off points and assays were determined by indirect immunofluorescense. Anti
      proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA.
      RESULTS: Most positivity for ANCA was seen in patients with ANCA associated,
      primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus
      erythematosus. Presence of ANCA without positivity for proteinase 3 and
      myeloperoxidase was higher in patients with ANA and little relation was observed
      between the perinuclear pattern confirmed in formalin and specificity by
      myeloperoxidase. Highest sensibility and specificity values for vasculitides
      diagnostic were achieved by ANCA determination using indirect immunofluorescense
      with a cut off 1/80 and confirming antigenic specificities with ELISA.
      CONCLUSION: ANCA can be present in a great number of chronic inflammatory or
      autoimmune disorders in the population studied. This determination using indirect
      immunofluorescence and following by ELISA had a great value for vasculitis
      diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin
      assay when ANA is present.

PMID- 24913966
TI  - Rheumatoid arthritis-associated interstitial lung disease: lung inflammation
      evaluated with high resolution computed tomography scan is correlated to
      rheumatoid arthritis disease activity.
AB  - OBJECTIVE: To describe the association between rheumatoid arthritis disease
      activity (RA) and interstitial lung damage (inflammation and fibrosis), in a
      group of patients with rheumatoid arthritis-associated interstitial lung disease
      (RA-ILD). METHODS: A retrospective study of RA patients with interstitial lung
      disease (restrictive pattern in lung function tests and evidence of interstitial
      lung disease in high resolution computed tomography (HRCT)). Patients were
      evaluated to exclude other causes of pulmonary disease. RA disease activity was
      measured with the CDAI index. Interstitial lung inflammation and fibrosis were
      determined by Kazerooni scale. We compared Kazerooni ground-glass score with the
      nearest CDAI score to HRCT date scan of the first medical evaluation at our
      institution. In nine patients, we compared the first ground-glass score with a
      second one after treatment with DMARDs and corticosteroids. Spearman's rank
      correlation coefficient was used to evaluate association between RA disease
      activity and the Kazerooni ground-glass and fibrosis scores. RESULTS: Thirty-four
      patients were included. A positive correlation between CDAI and ground-glass
      scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not
      associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the
      ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]),
      P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063.
      CONCLUSION: There is a correlation between RA disease activity and ground-glass
      appearance in the HRCT of RA-ILD patients. These results suggest a positive
      association between RA disease activity and lung inflammation in RA-ILD.

PMID- 24913967
TI  - Novel NDM-9 metallo-beta-lactamase identified from a ST107 Klebsiella pneumoniae
      strain isolated in China.

PMID- 24913969
TI  - The teen impact experience: a webcast pilot project for teens with cancer and
      blood diseases.
AB  - This article discusses a novel service, webcasting of a live group, implemented
      in response to the 2009-2010 H1N1 Flu pandemic by Teen Impact, a program geared
      at providing social therapy to adolescents diagnosed with cancer or a blood
      disorder. To ensure that services were not disrupted to adolescents on treatment
      despite flu restrictions, Teen Impact obtained necessary equipment to webcast the
      group. A total of 6 Teen Impact members participated in the webcast portion of
      the group. Findings revealed that existing members who had participated in the
      face-to-face Teen group were left with feelings of dissatisfaction due to lack of
      physical interaction with other members. New members appeared to enjoy this
      option admitting that the webcast provided them with the ability to feel
      supported by others with similar stories without having to face unknown members
      in person. A positive outcome from this type of intervention resulted in the
      webcast serving as a stepping stone for future face-to-face participation. 

PMID- 24913968
TI  - Regulatory role of the JNK-STAT1/3 signaling in neuronal differentiation of
      cultured mouse embryonic stem cells.
AB  - Stem cell transplantation therapy has provided promising hope for the treatment
      of a variety of neurodegenerative disorders. Among challenges in developing
      disease-specific stem cell therapies, identification of key regulatory signals
      for neuronal differentiation is an essential and critical issue that remains to
      be resolved. Several lines of evidence suggest that JNK, also known as SAPK, is
      involved in neuronal differentiation and neural plasticity. It may also play a
      role in neurite outgrowth during neuronal development. In cultured mouse
      embryonic stem (ES) cells, we test the hypothesis that the JNK pathway is
      required for neuronal differentiation. After neural induction, the cells were
      plated and underwent differentiation for up to 5 days. Western blot analysis
      showed a dramatic increase in phosphorylated JNKs at 1-5 days after plating. The
      phosphorylation of JNK subsequently induced activation of STAT1 and STAT3 that
      lead to expressions of GAP-43, neurofilament, betaIII-tubulin, and synaptophysin.
      NeuN-colabelled with DCX, a marker for neuroblast, was enhanced by JNK signaling.
      Neuronal differentiation of ES cells was attenuated by treatment with SP600125,
      which inhibited the JNK activation and decreased the activation of STAT1 and
      STAT3, and consequently suppressed the expressions of GAP-43, neurofilament,
      betaIII-tubulin, and the secretion of VEGF. Data from immunocytochemistry
      indicated that the nuclear translocation of STAT3 was reduced, and neurites of ES
      derived neurons were shorter after treatment with SP600125 compared with control
      cells. These results suggest that the JNK-STAT3 pathway is a key regulator
      required for early neuronal differentiation of mouse ES cells. Further
      investigation on expression of JNK isoforms showed that JNK-3 was significantly
      upregulated during the differentiation stage, while JNK-1 and JNK-2 levels
      decreased. Our study provided interesting information on JNK functions during ES
      cell neuronal differentiation.

PMID- 24913970
TI  - CD98 as a novel prognostic indicator for patients with stage III/IV
      hypopharyngeal squamous cell carcinoma.
AB  - BACKGROUND: Both L-type amino acid transporter 1 (LAT1) and CD98 are strongly
      expressed in primary human cancer and play essential roles in tumor growth. We
      studied the clinicopathological significance of LAT1 and CD98 expression in
      hypopharyngeal squamous cell carcinoma (SCC). METHODS: A total of 70 patients
      with stage III/IV disease were retrospectively reviewed. Immunohistochemical
      staining of tumor sections was used to examine LAT1, CD98, Ki-67, CD34, and p53.
      RESULTS: High LAT1 and CD98 expression were noted in 60.0% and 47.1%,
      respectively (p = .174). A statistically significant correlation was recognized
      between LAT1 and CD98 expression and both expressions were closely associated
      with tumor cell proliferation. Although LAT1 expression was not significantly
      associated with poor survival, multivariate analysis revealed high CD98
      expression to be an independent prognostic factor for predicting a poor outcome.
      CONCLUSION: CD98 is a promising prognostic marker for predicting outcomes after
      surgical treatment in patients with advanced hypopharyngeal SCC.

PMID- 24913971
TI  - Cytotoxicity of compounds from the fruits of Derris indica against
      cholangiocarcinoma and HepG2 cell lines.
AB  - Two new compounds, derrivanone (1) and derrischalcone (2), were isolated from the
      crude hexane extract of the fruits of Derris indica. In addition, 14 known
      compounds were isolated from the fruits of this plant. Chalcones 2-4 showed
      strong cytotoxicity against cholangiocarcinoma cell line (M156) and human
      hepatoma HepG2 cells. In addition, flavanones 15 and 16 exhibited potent and high
      cytotoxic efficacy. 

PMID- 24913972
TI  - Surgery for complex perineal fistula following rectal cancer treatment using
      biological mesh combined with gluteal perforator flap.
AB  - Three patients with complex perineal fistula after extensive pelvic surgery and
      radiotherapy underwent surgical treatment combining a biological mesh for pelvic
      floor reconstruction and a unilateral superior gluteal artery perforator (SGAP)
      flap for filling of the perineal defect. All patients had both fecal and urinary
      diversion. Two fistulas originated from the small bowel, necessitating parenteral
      feeding, and one from the bladder. Symptoms included severe sacral pain and skin
      maceration. After laparotomy with complete debridement of the pelvic cavity, the
      pelvic floor was reconstructed by stitching a biological mesh at the level of the
      pelvic outlet. Subsequently, patients were turned to prone position, and perineal
      reconstruction was completed by rotating a SGAP flap into the defect between the
      biomesh and the perineal skin. Operating time ranged from 10 to 12.5 h, and
      hospital stay lasted from 9 to 23 days. The postoperative course was uneventful
      in all three patients. Reconstruction of large pelvic defects with a combination
      of biological mesh and SGAP flap is a viable alternative to a rectus abdominis
      musculocutaneous flap and may be preferable after extensive pelvic surgery with
      ostomy.

PMID- 24913974
TI  - "Anterior resection syndrome" in a patient with neo-smooth muscle sphincter.

PMID- 24913973
TI  - Penetrating injury to the buttock: an update.
AB  - Clinical research on penetrating injury to the buttock is sparse and largely
      limited to case reports and clinical series. The purpose of this paper is to
      provide a detailed overview of literature of the topic and to propose a basic
      algorithm for management of penetrating gluteal injuries (PGI). MEDLINE, EMBASE,
      Cochran, and CINAHL databases were employed. Thirty-seven papers were selected
      and retrieved for overview from 1,021 records. PGI accounts for 2-3 % of all
      penetrating injuries, with a mortality rate up to 4 %. Most haemodynamically
      stable patients will benefit from traditional wound care and selective non
      operative management. When gluteal fascia injury is confirmed or suspected, a
      contrast-enhanced CT-scan provides the most accurate injury diagnosis. CT-scan
      based angiography and endovascular interventions radically supplement assessment
      and management of patients with penetrating injury to the major buttock and
      adjacent extra-buttock arteries. Immediate life-saving damage-control surgery is
      indicated for patients with hypovolemic shock and signs of internal bleeding. A
      universal basic management algorithm is proposed. This overview shows that
      penetrating injury to the buttock should be regarded as a potential life
      threatening injury, and therefore, patients with such injuries should be managed
      in trauma centres equipped with hybrid operating theatres for emergency
      endovascular and open surgery for multidisciplinary teams operating 24/7.

PMID- 24913975
TI  - MiR-29b downregulates canonical Wnt signaling by suppressing coactivators of beta
      catenin in human colorectal cancer cells.
AB  - The beta-catenin/Wnt signaling pathway is activated in many cancers and its
      constitutive activation has a central role in colorectal cancer pathogenesis.
      Recent studies have highlighted the role of microRNAs as novel regulators of gene
      expression including that of signaling intermediates from the Wnt signaling
      pathway. The purpose of our study was to determine the role of miR-29b in the
      regulation of Wnt signaling in human colorectal cancer cells. TOPFlash/FOPFlash
      reporter assays, gene expression studies by quantitative RT-PCR and western blot
      analysis were used to study the effect of ectopic expression of miR-29b on
      canonical Wnt signaling. miR-29b antagonized transactivation of beta-catenin
      target genes by downregulating coactivators of beta-catenin (TCF7L2, Snail, and
      BCL9L) in SW480 cells. miR-29b targeted the 3'UTR of BCL9L and decreased its
      expression with a consequent decrease in nuclear translocation of beta-catenin.
      Ectopic expression of miR-29b inhibited anchorage independent cell growth,
      promoted reversal of epithelial to mesenchymal transition and reduced the ability
      of conditioned medium from SW480 cells to induce in vitro tube formation in
      endothelial cells. These results have unraveled a novel role of miR-29b in Wnt
      signaling in human colorectal cancer cells with implications in the treatment of
      colorectal cancer.

PMID- 24913976
TI  - The peritrophic matrix mediates differential infection outcomes in the tsetse fly
      gut following challenge with commensal, pathogenic, and parasitic microbes.
AB  - The insect gut is lined by a protective, chitinous peritrophic matrix (PM) that
      separates immunoreactive epithelial cells from microbes present within the
      luminal contents. Tsetse flies (Glossina spp.) imbibe vertebrate blood
      exclusively and can be exposed to foreign microorganisms during the feeding
      process. We used RNA interference-based reverse genetics to inhibit the
      production of a structurally robust PM and then observed how this procedure
      impacted infection outcomes after per os challenge with exogenous bacteria
      (Enterobacter sp. and Serratia marcescens strain Db11) and parasitic African
      trypanosomes. Enterobacter and Serratia proliferation was impeded in tsetse that
      lacked an intact PM because these flies expressed the antimicrobial peptide gene,
      attacin, earlier in the infection process than did their counterparts that housed
      a fully developed PM. After challenge with trypanosomes, attacin expression was
      latent in tsetse that lacked an intact PM, and these flies were thus highly
      susceptible to parasite infection. Our results suggest that immunodeficiency
      signaling pathway effectors, as opposed to reactive oxygen intermediates, serve
      as the first line of defense in tsetse's gut after the ingestion of exogenous
      microorganisms. Furthermore, tsetse's PM is not a physical impediment to
      infection establishment, but instead serves as a barrier that regulates the fly's
      ability to immunologically detect and respond to the presence of these microbes.
      Collectively, our findings indicate that effective insect antimicrobial responses
      depend largely upon the coordination of multiple host and microbe-specific
      developmental factors. 

PMID- 24913977
TI  - Targeted delivery of alpha-galactosylceramide to CD8alpha+ dendritic cells
      optimizes type I NKT cell-based antitumor responses.
AB  - Immunotherapy aiming at enhancing innate and acquired host immunity is a
      promising approach for cancer treatment. The invariant NKT (iNKT) cell ligand
      alpha-galactosylceramide (alpha-GalCer) holds great promise in cancer therapy,
      although several concerns limit its use in clinics, including the uncontrolled
      response it promotes when delivered in a nonvectorized form. Therefore,
      development of delivery systems to in vivo target immune cells might be a
      valuable option to optimize iNKT cell-based antitumor responses. Using dendritic
      cell (DC)-depleted mice, DC transfer experiments, and in vivo active cell
      targeting, we show that presentation of alpha-GalCer by DCs not only triggers
      optimal primary iNKT cell stimulation, but also maintains secondary iNKT cell
      activation after challenge. Furthermore, targeted delivery of alpha-GalCer to
      CD8alpha(+) DCs, by means of anti-DEC205 decorated nanoparticles, enhances iNKT
      cell-based transactivation of NK cells, DCs, and gammadelta T cells. We report
      that codelivery of alpha-GalCer and protein Ag to CD8alpha(+) DCs triggers
      optimal Ag-specific Ab and cytotoxic CD8(+) T cell responses. Finally, we show
      that targeting nanoparticles containing alpha-GalCer and Ag to CD8alpha(+) DCs
      promotes potent antitumor responses, both in prophylactic and in therapeutic
      settings. Our data may have important implications in tumor immunotherapy and
      vaccine development. 

PMID- 24913978
TI  - Immune memory-boosting dose of rapamycin impairs macrophage vesicle acidification
      and curtails glycolysis in effector CD8 cells, impairing defense against acute
      infections.
AB  - Direct mammalian target of rapamycin (Rapa) complex 1 inhibition by short-term
      low-dose Rapa treatment has recently been shown to improve CD8 T cell
      immunological memory. Whereas these studies focused on memory development, the
      impact of low-dose Rapa on the primary immune response, particularly as it
      relates to functional effector immunity, is far less clear. In this study, we
      investigated the impact of acute Rapa treatment on immune effector cell function
      during the primary immune response to several acute infections. We found that
      functional CD8 T cell and macrophage responses to both viral and intracellular
      bacterial pathogens were depressed in mice in vivo and in humans to phorbol ester
      and calcium ionophore stimulation in vitro in the face of low-dose Rapa
      treatment. Mechanistically, the CD8 defect was linked to impaired glycolytic
      switch in stimulated naive cells and the reduced formation of short-lived
      effector cells. Therefore, more than one cell type required for a protective
      effector immune response is impaired by Rapa in both mice and humans, at the dose
      shown to improve immune memory and extend lifespan. This urges caution with
      regard to the relative therapeutic costs and benefits of Rapa treatment as means
      to improve immune memory. 

PMID- 24913979
TI  - Cytokine-regulated neutrophil recruitment is required for brain but not spinal
      cord inflammation during experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is an autoimmune disease in which inflammatory lesions
      lead to tissue injury in the brain and/or spinal cord. The specific sites of
      tissue injury are strong determinants of clinical outcome in MS, but the pathways
      that determine whether damage occurs in the brain or spinal cord are not
      understood. Previous studies in mouse models of MS demonstrated that IFN-gamma
      and IL-17 regulate lesion localization within the brain; however, the mechanisms
      by which these cytokines mediate their effects have not been identified. In the
      present study, we show that IL-17 promoted, but IFN-gamma inhibited, ELR(+)
      chemokine-mediated neutrophil recruitment to the brain, and that neutrophil
      infiltration was required for parenchymal tissue damage in the brain. In
      contrast, IFN-gamma promoted ELR(+) chemokine expression and neutrophil
      recruitment to the spinal cord. Surprisingly, tissue injury in the spinal cord
      did not exhibit the same dependence on neutrophil recruitment that was observed
      for the brain. Our results demonstrate that the brain and spinal cord exhibit
      distinct sensitivities to cellular mediators of tissue damage, and that IL-17 and
      IFN-gamma differentially regulate recruitment of these mediators to each
      microenvironment. These findings suggest an approach toward tailoring therapies
      for patients with distinct patterns of neuroinflammation. 

PMID- 24913980
TI  - Reactive oxygen species- and DNA damage response-dependent NK cell activating
      ligand upregulation occurs at transcriptional levels and requires the
      transcriptional factor E2F1.
AB  - Increasing evidence indicates that cancer cell stress induced by chemotherapeutic
      agents promote antitumor immune responses and contribute to their full clinical
      efficacy. In this article, we identify the signaling events underlying
      chemotherapy-induced NKG2D and DNAM-1 ligand expression on multiple myeloma (MM)
      cells. Our findings indicate that sublethal doses of doxorubicin and melphalan
      initiate a DNA damage response (DDR) controlling ligand upregulation on MM cell
      lines and patient-derived malignant plasma cells in Chk1/2-dependent and p53
      independent manner. Drug-induced MICA and PVR gene expression are
      transcriptionally regulated and involve DDR-dependent E2F1 transcription factor
      activity. We also describe the involvement of changes in the redox state in the
      control of DDR-dependent upregulation of ligand surface expression and gene
      transcriptional activity by using the antioxidant agent N-acetyl-L-cysteine.
      Finally, in accordance with much evidence indicating that DDR and oxidative
      stress are major determinants of cellular senescence, we found that redox
      dependent DDR activation upon chemotherapeutic treatment is critical for MM cell
      entry in premature senescence and is required for the preferential ligand
      upregulation on senescent cells, which are preferentially killed by NK cells and
      trigger potent IFN-gamma production. We propose immunogenic senescence as a
      mechanism that promotes the clearance of drug-treated tumor cells by innate
      effector lymphocytes, including NK cells.

PMID- 24913982
TI  - Self-assembly of collagen building blocks guided by electric fields.
AB  - Show me the way: protein building blocks are programmed to assemble
      hierarchically and yield a defined fiber morphology of micrometric length and
      precise nanometric diameter. The key step of this method is to align the building
      blocks with an AC field prior to assembly. The resulting protein nanofibers are
      straightforwardly integrated with the circuitry for potential applications in
      bionanotechnology. 

PMID- 24913981
TI  - Dual function of CD70 in viral infection: modulator of early cytokine responses
      and activator of adaptive responses.
AB  - The role of the TNF family member CD70 in adaptive T cell responses has been
      intensively studied, but its function in innate responses is still under
      investigation. In this study, we show that CD70 inhibits the early innate
      response to murine CMV (MCMV) but is essential for the optimal generation of
      virus-specific CD8 T cells. CD70(-/-) mice reacted to MCMV infection with a
      robust type I IFN and proinflammatory cytokine response. This response was
      sufficient for initial control of MCMV, although at later time points, CD70(-/-)
      mice became more susceptible to MCMV infection. The heightened cytokine response
      during the early phase of MCMV infection in CD70(-/-) mice was paralleled by a
      reduction in regulatory T cells (Treg). Treg from naive CD70(-/-) mice were not
      as efficient at suppressing T cell proliferation compared with Treg from naive
      wild-type mice, and depletion of Treg during MCMV infection in Foxp3-diphtheria
      toxin receptor mice or in wild-type mice recapitulated the phenotype observed in
      CD70(-/-) mice. Our study demonstrates that although CD70 is required for the
      activation of the antiviral adaptive response, it has a regulatory role in early
      cytokine responses to viruses such as MCMV, possibly through maintenance of Treg
      survival and function. 

PMID- 24913984
TI  - Pyridine analogues of spirocyclic sigma1 receptor ligands.
AB  - Spirocyclic benzopyrans 2 interact with high affinity and selectivity with sigma1
      receptors. Bioisosteric replacement of the benzene ring of the benzopyran
      substructure with the electron rich thiophene ring (3) led to increased sigma1
      affinity. Herein the synthesis and pharmacological evaluation of electron
      deficient pyridine bioisosteres 4 are reported. Homologation of the aldehyde 6 to
      afford the pyridylacetaldehyde derivative 8 was performed by a Wittig reaction.
      Bromine lithium exchange of the bromopyridine 8, addition to 1-benzylpiperidin-4
      one and cyclization led to the spirocyclic pyrranopyridine 10. Hydrogenolytic
      removal of the N-benzyl moiety of 10 provided the secondary amine 11, which
      allowed the introduction of various N-substituents (12a-d). Cyclization of the
      hydroxy acetal 9 with HCl led to various modifications of the substituent in 3'
      position. Generally the sigma1 affinity of the pyridine derivatives is reduced
      compared with those of the benzene and thiophene derivatives 2 and 3. However,
      the relationships between the structure and the sigma1 affinity follow the same
      rules as for the benzene and thiophene derivatives. The most promising sigma1
      ligand within this class of compounds is the pyranopyridine 15 with a double bond
      in the pyran ring revealing a Ki-value of 4.6 nM and a very high selectivity
      (>217-fold) over the sigma2 subtype.

PMID- 24913983
TI  - Controversies and challenges in research on urogenital schistosomiasis-associated
      bladder cancer.
AB  - Urogenital schistosomiasis, infection with Schistosoma haematobium, is linked to
      increased risk for the development of bladder cancer, but the importance of
      various mechanisms responsible for this association remains unclear, in part,
      owing to lack of sufficient and appropriate animal models. New advances in the
      study of this parasite, bladder regenerative processes, and human schistosomal
      bladder cancers may shed new light on the complex biological processes that
      connect S. haematobium infection to bladder carcinogenesis. 

PMID- 24913985
TI  - SAR studies of differently functionalized chalcones based hydrazones and their
      cyclized derivatives as inhibitors of mammalian cathepsin B and cathepsin H.
AB  - Cathepsins have emerged as potential drug targets for melanoma therapy and
      engrossed attention of researchers for development and evaluation of cysteine
      cathepsin inhibitors as cancer therapeutics. In this direction, we have designed,
      synthesized, and assayed in vitro a small library of 30 low molecular weight
      functionalized analogs of chalcone hydrazones for evaluating structure-activity
      relationship aspects and inhibitory potency against cathepsin B and H. The
      maximum inhibitory effect was exerted by chalcone hydrazones, which are open
      chain analogues followed by their cyclized derivatives, pyrazolines and
      pyrazoles. All the synthesized compounds were established as reversible
      inhibitors of these enzymes. Cathepsin B was selectively inhibited by the
      compounds in each series. Compounds 1d, 2d and 4d were recognized as most potent
      inhibitors of cathepsin B in this study with Ki values of 0.042 MUM, 0.053 MUM
      and 0.131 MUM whereas 1b (Ki=1.111 MUM), 2b (Ki=1.174 MUM) and 4b (Ki=1.562 MUM)
      inhibited cathepsin H activity effectively. And, preeminent cathepsin B
      inhibitors were -NO2 functionalized however, -Cl substituted moieties were the
      most persuasive inhibitors for cathepsin H among all the designed compounds.
      Molecular docking studies performed using iGemdock provided valuable insights.

PMID- 24913987
TI  - Molecular dynamics with helical periodic boundary conditions.
AB  - Helical symmetry is often encountered in nature and thus also in molecular
      dynamics (MD) simulations. In many cases, an approximation based on infinite
      helical periodicity can save a significant amount of computer time. However,
      standard simulations with the usual periodic boundary conditions (PBC) are not
      easily compatible with it. In the present study, we propose and investigate an
      algorithm comprising infinitely propagated helicity, which is compatible with
      commonly used MD software. The helical twist is introduced as a parametric
      geometry constraint, and the translational PBC are modified to allow for the
      helical symmetry via a transitional solvent volume. The algorithm including a
      parallel code was implemented within the Tinker software. The viability of the
      helical periodic boundary conditions (HPBC) was verified in test simulations
      including alpha-helical and polyproline II like peptide structures. For an
      insulin-based model, the HPBC dynamics made it possible to simulate a fibrillar
      structure, otherwise not stable within PBC.

PMID- 24913986
TI  - Risk of squamous cell skin cancer after organ transplant associated with
      antibodies to cutaneous papillomaviruses, polyomaviruses, and TMC6/8 (EVER1/2)
      variants.
AB  - Squamous cell skin cancer (SCSC) disproportionately affects organ transplant
      recipients, and may be related to increased viral replication in the setting of
      immune suppression. We conducted a nested case-control study among transplant
      recipients to determine whether SCSC is associated with antibodies to cutaneous
      human papillomaviruses (HPV), to genes associated with a rare genetic
      susceptibility to HPV (TMC6/TMC8), or to human polyomaviruses (HPyV). Cases (n =
      149) had histologically confirmed SCSC, and controls (n = 290) were individually
      matched to cases on time since transplant, type of transplant, gender, and race.
      All subjects had serum drawn immediately prior to transplant surgery. Antibodies
      to 25 cutaneous HPVs and six HPyVs were assayed by detection of binding to virus
      like particles, and 11 TMC6/8 variants were genotyped. After correction for
      multiple comparisons, only antibodies to HPV37 were associated with SCSC (OR 2.0,
      95% CI 1.2-3.4). Common genetic variants of TMC6/8 were not associated with SCSC,
      but three variants in TMC8 (rs12452890, rs412611, and rs7208422) were associated
      with greater seropositivity for species 2 betapapillomaviruses among controls.
      This study suggests that some betaHPVs, but not polyomaviruses, may play a role
      in the excess risk of SCSC among transplant recipients. 

PMID- 24913988
TI  - Utility of FDG-PET in clinical neuroendocrine prostate cancer.
AB  - BACKGROUND: Fluorodeoxyglucose (FDG) positron emission tomography (PET) has well
      characterized limitations in prostate adenocarcinoma (PCA). However, data
      assessing the utility of PET in neuroendocrine prostate cancer (NEPC) is limited
      to isolated case reports. Herein, we describe the first case series to assess the
      utility of FDG-PET in NEPC. METHODS: Inclusion criteria consisted of clinically
      progressive metastatic PCA in the setting of a chromogranin-A levels >1.5* the
      upper limit of normal, and >=1 FDG-PET scan after the diagnosis of NEPC, which
      yielded 23 patients. All metastatic lesions on CT, PET, and bone scan were read
      by two independent physicians. RESULTS: Five hundred ninety two unique lesions
      were identified across all imaging modalities, 510 were bone metastases, and 82
      were soft tissue metastases. Of bone lesions, 22.2%, 92.7%, and 77.6% were
      detected by PET, CT, and bone scan, respectively. Of soft tissue lesions, 95.1%
      and 97.5% were detected by PET and CT, respectively. Stratified by the median
      survival from NEPC diagnosis, patients who survived <2.2 versus >=2.2 years had
      more PET avid bone (8 vs. 2, P = 0.06) and soft tissue lesions (7 vs. 1, P =
      0.01), and higher average SUVmax of bone (5.49 vs. 3.40, P = 0.04) and soft
      tissue lesions (8.02 vs. 3.90, P = 0.0002). CONCLUSIONS: In patients with
      clinical NEPC, we demonstrate that FDG-PET has clinical utility in the detection
      of metastatic disease. In addition to detection, PET allows for treatment
      response to determine tumor viability. With novel therapies on the horizon to
      treat NEPC, consideration to investigate the use of FDG-PET to monitor response
      is warranted.

PMID- 24913989
TI  - Comparing different analysis methods for quantifying the MRI amide proton
      transfer (APT) effect in hyperacute stroke patients.
AB  - Amide proton transfer (APT) imaging is a pH mapping method based on the chemical
      exchange saturation transfer phenomenon that has potential for penumbra
      identification following stroke. The majority of the literature thus far has
      focused on generating pH-weighted contrast using magnetization transfer ratio
      asymmetry analysis instead of quantitative pH mapping. In this study, the widely
      used asymmetry analysis and a model-based analysis were both assessed on APT data
      collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6,
      median imaging time after onset = 2 hours 59 minutes). It was found that the
      model-based approach was able to quantify the APT effect with the lowest
      variation in grey and white matter (<= 13.8 %) and the smallest average contrast
      between these two tissue types (3.48 %) in the healthy volunteers. The model
      based approach also performed quantitatively better than the other measures in
      the hyperacute stroke patient APT data, where the quantified APT effect in the
      infarct core was consistently lower than in the contralateral normal appearing
      tissue for all the patients recruited, with the group average of the quantified
      APT effect being 1.5 +/- 0.3 % (infarct core) and 1.9 +/- 0.4 % (contralateral).
      Based on the fitted parameters from the model-based analysis and a previously
      published pH and amide proton exchange rate relationship, quantitative pH maps
      for hyperacute stroke patients were generated, for the first time, using APT
      imaging.

PMID- 24913990
TI  - [Severe or life-threatening interactions between antiretrovirals and non-HIV
      drugs].
AB  - Highly active antiretroviral therapy has helped to improved control of the HIV
      infection, and has led to a progressively older population with the infection
      having a life expectancy quite similar to that of the general population. On the
      other hand, it is also known that HIV infection, even in patients with
      undetectable viral loads and good immunity, carries an increased cardiovascular
      risk, as well as an increased incidence of certain cancers. Therefore, the
      majority of HIV-infected patients receive several drugs (either prescribed by the
      physician or self-administered) combined with antiretrovirals. This article
      reviews the interactions between antiretrovirals and other drugs that can cause
      significant damage to patients, or even be life-threatening and of whom
      clinicians, especially those not directly treating HIV-infected patients, should
      be aware. A review is also presented on the implications of interactions between
      antiretrovirals and other drugs in special situations, such as the co
      administration with cytostatics, immunesuppressants used in solid organ
      transplantation, or patients receiving new treatments for hepatitisC. Generally,
      combinations with two nucleos(t)ide reverse transcriptase inhibitors and
      raltegravir (or in the near future, dolutegravir) are those with less potential
      for clinically significant interactions.

PMID- 24913991
TI  - [Rhabdomyolysis and severe hepatotoxicity due to a drug-drug interaction between
      ritonavir and simvastatin. Could we use the most cost-effective statin in all
      human immunodeficiency virus-infected patients?].
AB  - INTRODUCTION: Drugs like statins may induce rhabdomyolysis. Simvastatin and
      lovastatin have a high hepatic metabolism and their potential toxicity could be
      increased by interactions with other drugs that reduce their metabolism. PATIENTS
      AND METHODS: A case-report is presented of an HIV-infected patient treated with
      antiretroviral drugs who developed a rhabdomyolysis-induced renal failure and
      liver toxicity when simvastatin was substituted for atorvastatin. A literature
      review is also presented. RESULTS: The patient required hospital admission and
      showed a favorable response after hydration and urine alkalinization. There were
      4 additional cases published of which there was one death. CONCLUSIONS: Drug-drug
      interactions can increase the risk of statin induced rhabdomyolysis. In order to
      evaluate them properly, physicians at all levels of clinical care should be aware
      of all drugs prescribed to their patients and the contraindicated combinations.

PMID- 24913992
TI  - Emergence of quinolone-resistant, topoisomerase-mutant Brucella after treatment
      with fluoroquinolones in a macrophage experimental infection model.
AB  - AIM OF THE STUDY: To determine the activity of fluoroquinolones (FQ) and the
      selection of FQ-resistant mutants in a macrophage experimental infection model
      (MEIM). MATERIAL AND METHODS: Canine macrophages were inoculated with Brucella
      melitensis ATCC 23457 (WT), achieving intracellular counts of around 105 CFU/mL.
      Cell cultures were incubated in the presence of ciprofloxacin (CIP), levofloxacin
      (LEV), moxifloxacin (MOX), and doxycycline (DOX). After cell lysis, surviving
      microorganisms were plated for count purposes, and plated onto antibiotics
      containing media for mutant selection. Topoisomerases mutations were detected by
      PCR and sequencing. RESULTS: Bacterial counts after cell lysis were 14.3% (CIP),
      65.3% (LEV), and 75% (MOX) lower compared to the control. Quinolone-resistant
      mutants emerged in cell cultures containing CIP and LEV with a frequency of
      around 0.5*10(-3). All mutants showed an Ala87Val change in GyrA. Mutants had FQs
      MICs around 10*WT. The ability of these mutants for infecting new macrophages and
      the intracellular lysis after antibiotic exposure did not change significantly.
      No 2nd step FQ-resistant mutants were selected from 1st step mutants.
      CONCLUSIONS: Intracellular activity of FQs is low against WT and gyrA-mutant
      Brucella. FQs easily select gyrA mutants in MEIM. The ability of mutants for
      infecting new macrophages remains unchanged. In this MEIM, 2nd step mutants do
      not emerge.

PMID- 24913993
TI  - [Cerebral toxoplasmosis in a patient with Waldenstrom's macroglobulinemia].

PMID- 24913995
TI  - An interview with Raymond L. Woosley.

PMID- 24913994
TI  - [Diabetic foot osteomyelitis: is conservative treatment possible?].
AB  - INTRODUCTION: The aim of the present study is to determine the proportion of foot
      ulcers, complicated by osteomyelitis in diabetic patients, that heal without
      amputation. Furthermore, an attempt is made to analyze the main clinical and
      microbiological characteristics of episodes, and to identify potential predictive
      factors leading to the failure of conservative treatment. METHODS: A prospective
      observational study was carried out between 2007 and 2009 on diabetic patients
      with a foot lesion and attending a diabetic foot clinic. A percutaneous bone
      biopsy was required to be included in the study. RESULTS: A total of 81 episodes
      of diabetic foot osteomyelitis in 64 patients were evaluated. Staphylococcus
      aureus (28/81) and coagulase negative Staphylococcus (22/81) were the most
      frequent organisms isolated. Among the gramnegative group (34/81), non-fermenting
      gram negative bacteria were the most prevalent organisms isolated (14/81).
      Conservative treatment was successful in 73% of episodes. After a logistic
      regression analysis using the most significant prognostic variables, only lesion
      size greater than 2cm independently predicted failure of conservative treatment.
      Culture guided antibiotic treatment was associated with a better prognosis.
      CONCLUSION: Conservative treatment, including culture-guided antibiotics, is
      successful without amputation in a large proportion of diabetic patients with
      diabetic foot osteomyelitis. Considering empiric therapy directed at non
      fermenting gramnegative bacteria could be advisable in some cases, because they
      are frequently isolated in our setting.

PMID- 24913996
TI  - Prognostic factors of Bell's palsy: multivariate analysis of electrophysiological
      findings.
AB  - OBJECTIVES/HYPOTHESIS: The study was designed to verify if one or more
      electrophysiological parameters could predict a risk of nonrecovery of normal
      facial function and the development of synkinesis in Bell's palsy (BP) subjects.
      STUDY DESIGN: Prospective case series. METHODS: A total of 120 subjects ranging
      from 18 to 70 years with unilateral BP (International Classification of Disease
      11), Grade III to VI House-Brackmann (HB) degree, were assessed and treated with
      standardized oral steroids and antiviral drugs within 48 hours from onset. Of
      these, 92 underwent electroneurography (ENoG), electromyography (EMG), and blink
      reflex (BR) testing at 7 to 10 and 20 days after palsy onset. Multivariate
      analysis and receiver operating characteristic curves were carried out to verify
      which combination of electrophysiological parameters may be predictive of no
      recovery and/or development of synkinesis. RESULTS: BR and ENoG were the best
      predictors of no facial function recovery, showing significant correlation
      coefficient with severity of facial palsy in both assessments. EMG findings did
      not add any prognostic significance. Worsening of facial palsy can be observed in
      subjects despite steroid therapy. The risk of developing synkinesis might be
      evaluated soon after BP on the grounds of ENoG degeneration, orbicularis oculi
      denervation, a younger age, and severe (V-VI) HB grade. CONCLUSIONS: BR and ENoG,
      considered together with clinical findings, could offer a good indication in the
      first phases of BP for the possibility to develop palsy residua. This combination
      of tests is well accepted by the subjects, and is therefore suitable for multiple
      assessments in the early postpalsy period.Key Words: Bell's palsy, facial palsy,
      ENoG, blink reflex, Prognosis. LEVEL OF EVIDENCE: 4.

PMID- 24913997
TI  - Increased thrombin generation in splanchnic vein thrombosis is related to the
      presence of liver cirrhosis and not to the thrombotic event.
AB  - INTRODUCTION: In recent years there have been increasing evidence associating
      liver disease with hypercoagulability, rather than bleeding. The aim of the study
      was to evaluate the haemostatic potential in patients with liver disease.
      PATIENTS AND METHODS: We measured thrombin generation in the presence and absence
      of thrombomodulin in patients with portal vein thrombosis (PVT, n=47), Budd
      Chiari syndrome (BCS, n=15) and cirrhosis (n=24) and compared the results to
      those obtained from healthy controls (n=21). Fifteen patients with PVT and 10
      patients with BCS were treated with warfarin and were compared to an equal number
      of patients with atrial fibrillation matched for prothrombin time-international
      normalized ratio. We assessed resistance to thrombomodulin by using ratios
      [marker measured in the presence/absence of thrombomodulin]. RESULTS: There were
      no differences in thrombin generation between patients on warfarin treatment and
      their controls. Cirrhotic patients generated more thrombin in the presence of
      thrombomodulin and exhibited thrombomodulin resistance compared to controls
      [p=0.006 for endogenous thrombin potential (ETP) and p<0.001 for peak thrombin
      and both ratios ETP and peak] and patients with non-cirrhotic PVT (p=0.001,
      p=0.006, p<0.001, p<0.001 for ETP, peak, ratio ETP, ratio peak, respectively).
      The patients with cirrhotic PVT exhibited higher ETP (p=0.044) and peak (p=0.02)
      in the presence of thrombomodulin than controls, as well as thrombomodulin
      resistance (ETP and peak ratios: p=0.001). CONCLUSIONS: Hypercoagulability and
      thrombomodulin resistance in patients with cirrhosis were independent of the
      presence of splanchnic vein thrombosis. The hypercoagulability in patients with
      cirrhotic PVT could have implications for considering longer or more intensive
      treatment with anticoagulants in this group.

PMID- 24913998
TI  - Evaluating errors in the laboratory identification of von Willebrand disease in
      the real world.
AB  - INTRODUCTION: von Willebrand disease (VWD), reportedly the most common bleeding
      disorder, arises from deficiency and/or defects of von Willebrand factor (VWF).
      Assessment requires a wide range of tests, including VWF activity and antigen.
      Appropriate diagnosis including differential identification of qualitative vs
      quantitative defects has important management implications, but remains
      problematic for many laboratories and clinicians. METHODS: Data using a large set
      (n=29) of varied plasma samples comprising both 'quantitative' VWF deficiency
      ('Type 1 and 3' VWD) vs 'qualitative' defects ('Type 2 VWD') tested in a cross
      laboratory setting has been evaluated to assess the ability of real world
      laboratories to differentially identify these sample types. RESULTS: Different
      VWF assays and activity/antigen ratios show different utility in VWD and type
      identification. VWD identification errors were often linked to high inter
      laboratory test variation and result misinterpretation (i.e., laboratories failed
      to correctly interpret their own test panel findings). Thus, moderate
      quantitative VWF deficient samples were misinterpreted as qualitative defects on
      30/334 occasions (9% error rate); 17% of these errors were due to laboratories
      misinterpreting their own data, which was instead consistent with quantitative
      deficiencies. Conversely, whilst qualitative VWF defects were misinterpreted as
      quantitative deficiencies at a similar error rate (~9%), this was more often due
      to laboratories misinterpreting their data (~50% of errors). For test-associated
      errors, ristocetin cofactor was associated with the highest variability and error
      rate, which was at least twice that using collagen binding. CONCLUSION: These
      findings in part explain the high rate of errors associated with VWD diagnosis.

PMID- 24913999
TI  - Bleeding complications in patients with coronary stents during non-cardiac
      surgery.
AB  - INTRODUCTION: Patients with coronary stents often undergo non-cardiac invasive
      procedures. These are often associated with thrombotic and/or hemorrhagic
      complications. The type of procedure, perioperative antiplatelet therapy, and
      other patient-related factors influence the risk of postoperative haemorrhage.
      Our objective was to analyze the postoperative risk factors for hemorrhagic
      complications and to determine the impact of antiplatelet and anticoagulant
      therapy strategies on postoperative bleeding risk in patients with coronary
      stents undergoing non-cardiac surgery. PATIENTS AND METHODS: Prospective,
      multicentre observational cohort study of 1134 consecutive patients with coronary
      stents undergoing non-cardiac surgery between April 2007 and April 2009. The
      primary outcome measure was the occurrence of an hemorrhagic complication during
      the first 30days following the surgery or intervention. RESULTS: Among the 1134
      patients evaluated, 108 (9.5%) experienced a postoperative hemorrhagic
      complication (with a median time to occurrence of 5.3days). These complications
      were considered major, involved the operative site, and required reoperation in
      92 (85.2%), 92 (85.2%), and 20 (18.5%) of patients, respectively. Mortality in
      patients with a haemorrhagic complication was 12% (n=13). Independent
      postoperative factors associated with haemorrhagic complications were identified
      as a high and intermediate bleeding risk procedure and the use and dose of
      anticoagulants. When interrupted before the procedure, resumption of antiplatelet
      treatment was delayed in patients developing early postoperative hemorrhagic
      complications. CONCLUSION: Patients with coronary stents who undergo surgery are
      at high risk for hemorrhagic complications.

PMID- 24914000
TI  - Daily variations in the glycerol-3-phosphate dehydrogenase isoforms expression in
      Triatoma infestans flight muscles.
AB  - Triatoma infestans, the main vector of Chagas disease, is a blood-sucking insect.
      Flight dispersal of adults is the most important mechanism for reinfestation of
      houses after insecticide spraying. Flight muscles have two glycerol-3-phosphate
      dehydrogenase (GPDH) isoforms: GPDH-1 is involved in flight metabolism and GPDH-2
      provides lipid precursors. In this study, we explored the profile of GPDH
      expression in females and males adult flight muscles under light/dark cycle,
      constant light, and constant dark conditions. Under constant dark conditions,
      GPDH-1 flight muscles of T. infestans showed a rhythmic pattern of transcription
      synchronous with a rhythmic profile of activity suggesting regulation by the
      endogenous circadian clock. Otherwise, the GPDH-2 expression analysis showed no
      regulation by the endogenous clock, but showed that an external factor, such as
      the dark/light period, was necessary for synchronization of GPDH-2 transcription
      and activity. 

PMID- 24914001
TI  - Seroprevalence of seven zoonotic pathogens in pregnant women from the Caribbean.
AB  - Studies examining the prevalence of zoonotic agents in the Caribbean are very
      limited. The objective of this study was to examine the seroprevalence of seven
      zoonotic agents among individuals residing on 10 English-speaking Caribbean
      countries. Sera from healthy, pregnant women were collected from Antigua-Barbuda,
      Belize, Bermuda, Dominica, Grenada, Jamaica, Montserrat, St. Kitts-Nevis, St.
      Lucia, and St. Vincent-Grenadines and tested for the presence of IgG antibodies
      to dengue virus, hepatitis E virus, hantaviruses, leptospiral agents, spotted
      fever group rickettsiae (SFGR), typhus group rickettsiae (TGR), and Coxiella
      burnetii (Q fever). The highest seroprevalence values were observed for dengue
      virus, SFGR, and leptospirosis, although the lowest seroprevalence values were
      observed for hepatitis E virus, C. burnetii, and TGR. Antibodies to hantaviruses
      were not detected in any individuals. 

PMID- 24914002
TI  - Wound care in Buruli ulcer disease in Ghana and Benin.
AB  - Buruli ulcer (BU) is a disease affecting the skin, subcutaneous fat, and bone
      tissues. Wound care is important in the prevention of disabilities. Awareness of
      current wound care practices in BU-endemic regions is necessary for future wound
      care interventions. Thirty-one health care workers in Ghana and Benin were
      interviewed with a semi-structured interview, complemented by structural
      observations. Quantitative data were analyzed through t tests and one-way
      analysis of variance, and qualitative data through descriptive statistics. There
      appeared to be a general understanding of wound assessment. A large variety of
      different topical antiseptics was reported to be used, pressure irrigation was
      never reported. Gauze was the main dressing type and a moist environment was
      preferred, but could not be maintained. Bleeding and pain were observed
      frequently. Standard of wound care differed importantly between health care
      personnel and between institutions and adherence to World Health Organization
      guidelines was low. 

PMID- 24914003
TI  - Microbiological evaluation of the efficacy of soapy water to clean hands: a
      randomized, non-inferiority field trial.
AB  - We conducted a randomized, non-inferiority field trial in urban Dhaka, Bangladesh
      among mothers to compare microbial efficacy of soapy water (30 g powdered
      detergent in 1.5 L water) with bar soap and water alone. Fieldworkers collected
      hand rinse samples before and after the following washing regimens: scrubbing
      with soapy water for 15 and 30 seconds; scrubbing with bar soap for 15 and 30
      seconds; and scrubbing with water alone for 15 seconds. Soapy water and bar soap
      removed thermotolerant coliforms similarly after washing for 15 seconds (mean
      log10 reduction = 0.7 colony-forming units [CFU], P < 0.001 for soapy water; mean
      log10 reduction = 0.6 CFU, P = 0.001 for bar soap). Increasing scrubbing time to
      30 seconds did not improve removal (P > 0.05). Scrubbing hands with water alone
      also reduced thermotolerant coliforms (mean log10 reduction = 0.3 CFU, P = 0.046)
      but was less efficacious than scrubbing hands with soapy water. Soapy water is an
      inexpensive and microbiologically effective cleansing agent to improve
      handwashing among households with vulnerable children. 

PMID- 24914004
TI  - Management of a chest-wall soft-tissue tumor caused by an infection with the
      larval tapeworm pathogen Taenia crassiceps.
AB  - A chest-wall lesion of an immunocompetent patient was initially suspicious for a
      malignant tumor. Histopathological and polymerase chain reaction examinations
      revealed an infection with the larval stage of the tapeworm Taenia crassiceps.
      Curative resection of the tumorous lesion was performed. Treatment options for
      immunocompromised patients and patients without known immune defect are
      discussed, because most of the infections occur in immunocompromised individuals.

PMID- 24914006
TI  - Neural signatures of the interaction between the 5-HTTLPR genotype and stressful
      life events in healthy women.
AB  - A change in neural connectivity of brain structures implicated in the memory of
      negative life events has been hypothesized to explain the enhancement of memory
      encoding during the processing of negative stimuli in depressed patients. Here,
      we investigated the effects of the interaction between negative life events and
      the 5-HTTLPR genotype - a polymorphism of the serotonin transporter gene - on the
      functional and structural connectivity of the hippocampal area in 34 healthy
      women. All participants were genotyped for the presence of the 5-HTTLPR short
      variant and for the A/G single-nucleotide polymorphism; they underwent clinical
      assessment including structured diagnostic interviews to exclude the presence of
      psychiatric disorders and to assess the presence of stressful life events.
      Resting state functional magnetic resonance imaging and diffusion tensor imaging
      scans were performed. We found significant interactions between stressful events
      and the 5-HTTLPR genotype in both the functional connectivity of the
      parahippocampus with the posterior cingulate cortex and the structural
      connectivity between the hippocampus and both the amygdala and the putamen. In
      addition, we found several genotype-related differences in the relationship
      between functional/structural connectivity of the hippocampal area and the
      ability to update expectations or stress-related phenotypes, such as anxiety
      symptoms. If confirmed by future studies, these mechanisms may clarify the role
      of the 5HTTLPR genotype as a risk factor for depression, in interaction with
      negative events. 

PMID- 24914005
TI  - Abstinent adult daily smokers show reduced anticipatory but elevated saccade
      related brain responses during a rewarded antisaccade task.
AB  - Chronic smoking may result in reduced sensitivity to non-drug rewards (e.g.,
      money), a phenomenon particularly salient during abstinence. During a quit
      attempt, this effect may contribute to biased decision-making
      (smoking>alternative reinforcers) and relapse. Although relevant for quitting,
      characterization of reduced reward function in abstinent smokers remains limited.
      Moreover, how attenuated reward function affects other brain systems supporting
      decision-making has not been established. Here, we use a rewarded antisaccade
      (rAS) task to characterize non-drug reward processing and its influence on
      inhibitory control, key elements underlying decision-making, in abstinent smokers
      vs. non-smokers. Abstinent (12-hours) adult daily smokers (N=23) and non-smokers
      (N=11) underwent fMRI while performing the rAS. Behavioral performances improved
      on reward vs. neutral trials. Smokers showed attenuated activation in ventral
      striatum during the reward cue and in superior precentral sulcus and posterior
      parietal cortex during response preparation, but greater responses during the
      saccade response in posterior cingulate and parietal cortices. Smokers'
      attenuated anticipatory responses suggest reduced motivation from monetary
      reward, while heightened activation during the saccade response suggests that
      additional circuitry may be engaged later to enhance inhibitory task performance.
      Overall, this preliminary study highlights group differences in decision-making
      components and the utility of the rAS to characterize these effects.

PMID- 24914008
TI  - Pyranosides with 2,3-trans carbamate groups: exocyclic or endocyclic cleavage
      reaction?
AB  - Pyranosides with 2,3-trans carbamate groups exhibit high 1,2-cis selectivity in
      glycosylation reactions. Using glycosyl donors with N-benzyl 2,3-trans carbamate
      groups, an anti-Helicobacter pylori oligosaccharide was synthesized in an
      efficient manner. Moreover, pyranosides with 2,3-trans carbamate groups readily
      undergo anomerization from the beta to the alpha configuration under mild acidic
      conditions via endocyclic cleavage. Acyclic cations generated during the
      endocyclic cleavage reaction were captured using reduction and intramolecular
      Friedel-Crafts reaction. By exploiting this anomerization, multiply aligned 1,2
      trans glycosyl bonds can be transformed to 1,2-cis glycosyl bonds in a single
      operation. 

PMID- 24914009
TI  - Editorial.

PMID- 24914010
TI  - A novel non-stop mutation in MSX1 causing autosomal dominant non-syndromic
      oligodontia.
AB  - Oligodontia, which is the congenital absence of six or more permanent teeth,
      excluding the third molars, may contribute to masticatory dysfunction, speech
      alteration, aesthetic problems and malocclusion. Msh homeobox 1 (MSX1) was the
      first gene identified as causing non-syndromic oligodontia. In this study, we
      identified a novel heterozygous non-stop mutation (c.910_911dupTA,
      p.*304Tyrext*48) in MSX1 in a Chinese family with autosomal dominant non
      syndromic oligodontia. This novel mutation substitutes the stop codon with a
      tyrosine residue, potentially adding 48 amino acids to the C-terminus of MSX1.
      Further in vitro study found that mutant MSX1 could be expressed but had lost its
      ability to enter the nucleus. This is the first report indicating that a non-stop
      mutation in MSX1 is responsible for oligodontia. This study broadens the mutation
      spectrum for MSX1 and provides a new way to clarify the mechanism of MSX1 in
      tooth agenesis. 

PMID- 24914011
TI  - Perceptual Underpinnings of Antigay Prejudice: Negative Evaluations of Sexual
      Minority Women Arise on the Basis of Gendered Facial Features.
AB  - Psychologists have amassed robust evidence of antigay prejudice by assessing
      participants' global attitudes toward sexual minorities and their reactions to
      behavioral descriptions of hypothetical targets. In daily interactions, however,
      perceivers make decisions about others' sexual orientations based upon visible
      cues alone. Does antigay prejudice arise on the basis of such visual exposure,
      and if so, why? Three studies revealed that perceivers evaluated women they
      categorized as lesbians more negatively than women they categorized as straight.
      Moreover, prejudice against lesbian women was strongly tethered to gendered
      aspects of their facial appearance: Women categorized as lesbians tended to
      appear gender-atypical, and women who appeared gender-atypical were perceived to
      be unattractive, leading to prejudice. Similar findings did not emerge for men
      categorized as gay. As such, we argue that gendered appearance cues lay the
      perceptual foundation for prejudice against women, but not men, who are
      categorized as sexual minorities.

PMID- 24914012
TI  - Remind Me Who I Am: Social Interaction Strategies for Maintaining the Threatened
      Self-Concept.
AB  - After failure, individuals frequently turn to others for support. The current
      research examined the process through which individuals utilize interpersonal
      relationships to stabilize threatened self-views. We may seek support to reassure
      us with warmth and acceptance after a self-threat, or to provide support for
      threatened self-knowledge. We proposed that although both types of support are
      likely to repair the affective consequences of a self-threat, only interacting
      with others who can provide evidence from the individuals' past that reconfirms a
      threatened self-aspect would help stabilize the self-concept. Two studies
      demonstrated that, for individuals who have suffered a self-threat, receiving
      specific evidentiary support for the threatened self-aspect was more effective at
      restoring confidence in both the specific self-aspect and at recovering self
      concept clarity than was receiving emotional support, whether the interaction was
      imagined (Study 1), or offered in person (Study 2) after the threat.

PMID- 24914007
TI  - The intermediates take it all: asymptotics of higher criticism statistics and a
      powerful alternative based on equal local levels.
AB  - The higher criticism (HC) statistic, which can be seen as a normalized version of
      the famous Kolmogorov-Smirnov statistic, has a long history, dating back to the
      mid seventies. Originally, HC statistics were used in connection with goodness of
      fit (GOF) tests but they recently gained some attention in the context of testing
      the global null hypothesis in high dimensional data. The continuing interest for
      HC seems to be inspired by a series of nice asymptotic properties related to this
      statistic. For example, unlike Kolmogorov-Smirnov tests, GOF tests based on the
      HC statistic are known to be asymptotically sensitive in the moderate tails,
      hence it is favorably applied for detecting the presence of signals in sparse
      mixture models. However, some questions around the asymptotic behavior of the HC
      statistic are still open. We focus on two of them, namely, why a specific
      intermediate range is crucial for GOF tests based on the HC statistic and why the
      convergence of the HC distribution to the limiting one is extremely slow.
      Moreover, the inconsistency in the asymptotic and finite behavior of the HC
      statistic prompts us to provide a new HC test that has better finite properties
      than the original HC test while showing the same asymptotics. This test is
      motivated by the asymptotic behavior of the so-called local levels related to the
      original HC test. By means of numerical calculations and simulations we show that
      the new HC test is typically more powerful than the original HC test in normal
      mixture models. 

PMID- 24914013
TI  - How is the electronic health record being used? Use of EHR data to assess
      physician-level variability in technology use.
AB  - BACKGROUND: Studies of the effects of electronic health records (EHRs) have had
      mixed findings, which may be attributable to unmeasured confounders such as
      individual variability in use of EHR features. OBJECTIVE: To capture physician
      level variations in use of EHR features, associations with other predictors, and
      usage intensity over time. METHODS: Retrospective cohort study of primary care
      providers eligible for meaningful use at a network of federally qualified health
      centers, using commercial EHR data from January 2010 through June 2013, a period
      during which the organization was preparing for and in the early stages of
      meaningful use. RESULTS: Data were analyzed for 112 physicians and nurse
      practitioners, consisting of 430,803 encounters with 99,649 patients. EHR usage
      metrics were developed to capture how providers accessed and added to patient
      data (eg, problem list updates), used clinical decision support (eg, responses to
      alerts), communicated (eg, printing after-visit summaries), and used panel
      management options (eg, viewed panel reports). Provider-level variability was
      high: for example, the annual average proportion of encounters with problem lists
      updated ranged from 5% to 60% per provider. Some metrics were associated with
      provider, patient, or encounter characteristics. For example, problem list
      updates were more likely for new patients than established ones, and alert
      acceptance was negatively correlated with alert frequency. CONCLUSIONS: Providers
      using the same EHR developed personalized patterns of use of EHR features. We
      conclude that physician-level usage of EHR features may be a valuable additional
      predictor in research on the effects of EHRs on healthcare quality and costs.

PMID- 24914014
TI  - Electronic medical record systems are associated with appropriate placement of
      HIV patients on antiretroviral therapy in rural health facilities in Kenya: a
      retrospective pre-post study.
AB  - BACKGROUND AND OBJECTIVE: There is little evidence that electronic medical record
      (EMR) use is associated with better compliance with clinical guidelines on
      initiation of antiretroviral therapy (ART) among ART-eligible HIV patients. We
      assessed the effect of transitioning from paper-based to an EMR-based system on
      appropriate placement on ART among eligible patients. METHODS: We conducted a
      retrospective, pre-post EMR study among patients enrolled in HIV care and
      eligible for ART at 17 rural Kenyan clinics and compared the: (1) proportion of
      patients eligible for ART based on CD4 count or WHO staging who initiate therapy;
      (2) time from eligibility for ART to ART initiation; (3) time from ART initiation
      to first CD4 test. RESULTS: 7298 patients were eligible for ART; 54.8% (n=3998)
      were enrolled in HIV care using a paper-based system while 45.2% (n=3300) were
      enrolled after the implementation of the EMR. EMR was independently associated
      with a 22% increase in the odds of initiating ART among eligible patients
      (adjusted OR (aOR) 1.22, 95% CI 1.12 to 1.33). The proportion of ART-eligible
      patients not receiving ART was 20.3% and 15.1% for paper and EMR, respectively
      (chi(2)=33.5, p<0.01). Median time from ART eligibility to ART initiation was
      29.1 days (IQR: 14.1-62.1) for paper compared to 27 days (IQR: 12.9-50.1) for
      EMR. CONCLUSIONS: EMRs can improve quality of HIV care through appropriate
      placement of ART-eligible patients on treatment in resource limited settings.
      However, other non-EMR factors influence timely initiation of ART.

PMID- 24914015
TI  - Polymeric micellar co-delivery of resveratrol and curcumin to mitigate in vitro
      doxorubicin-induced cardiotoxicity.
AB  - Resveratrol (RES) and curcumin (CUR) have free radical scavenging ability and
      potential chemosensitizing effects. Doxorubicin hydrochloride (DH) is a potent
      chemotherapeutic with severe cardiotoxicity. We hypothesize that RES and CUR co
      loaded in Pluronic((r)) micelles and co-administered with DH will result in
      cardioprotective effects while maintaining/improving DH anti-proliferative effect
      in vitro. RES-CUR at a molar ratio of 5:1 in F127 micelles (mRC) were prepared
      and characterized for size, drug loading, and release. In vitro cell viability
      and apoptosis assays in ovarian cancer cells (SKOV-3) and cardiomyocytes (H9C2)
      with either individual drugs or RES-CUR or mRC in combination with DH were
      conducted. Combination index (CI) analysis was performed to determine combination
      effects. Reactive oxygen species (ROS) were quantified in H9C2 for DH, and
      combinations. The mRC solubilized 2.96 and 0.97 mg/mL of RES and CUR,
      respectively. Cell viability and CI studies indicated that the combinations were
      synergistic in SKOV-3 and antagonistic in H9C2 cells. Caspase 3/7 activity in
      combination treatments was lower than with DH alone in both cell lines. ROS
      activity was restored to baseline in H9C2 cells in the micelle combination
      groups. Co-administration of mRC with DH in vitro mitigates DH-induced
      cardiotoxicity through reduction in apoptosis and ROS while improving DH potency
      in ovarian cancer cells.

PMID- 24914016
TI  - Sudden cardiac death early after myocardial infarction: pathogenesis, risk
      stratification, and primary prevention.

PMID- 24914019
TI  - Two classic hemodynamic findings for hypertrophic cardiomyopathy.

PMID- 24914018
TI  - Use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography
      and sonication for detection of infection after peripheral stent fracture.

PMID- 24914020
TI  - Subcutaneous implantable cardioverter-defibrillator.

PMID- 24914021
TI  - Letter by Ristagno and Li regarding article, "waveform analysis-guided treatment
      versus a standard shock-first protocol for the treatment of out-of-hospital
      cardiac arrest presenting in ventricular fibrillation: results of an
      international randomized, controlled trial".

PMID- 24914025
TI  - When the penny drops.

PMID- 24914022
TI  - Response to letter regarding article, "waveform analysis-guided treatment versus
      a standard shock-first protocol for the treatment of out-of-hospital cardiac
      arrest presenting in ventricular fibrillation: results of an international
      randomized, controlled trial".

PMID- 24914026
TI  - Sleeping in fits and starts: a practical guide to distinguishing nocturnal
      epilepsy from sleep disorders.
AB  - Accurately diagnosing sleep-related events, and particularly distinguishing
      nocturnal frontal lobe seizures from other sleep disorders such as parasomnias,
      can be challenging. This article reviews the differential diagnosis of paroxysmal
      events from sleep, epileptic and non-epileptic, considers important diagnostic
      points in the history, and evaluates the role of investigations in this setting. 

PMID- 24914028
TI  - The complexity after simplicity: how to proceed with renal denervation in
      hypertension?

PMID- 24914027
TI  - Association of age and gender with risk for non-ST-elevation myocardial
      infarction.
AB  - BACKGROUND: Age and gender associated risks for non-ST-elevation myocardial
      infarction (NSTEMI) at the population level are largely uncharacterized. DESIGN:
      Nationwide, population (26,724,165 person-years) based eight-year registry-study
      in Finland. METHODS: Gender- and age-associated frequency and incidence of NSTEMI
      were studied using a nationwide, population based registry of hospital admissions
      in patients aged >=30 years during 2001-2008. Patients with NSTEMI as primary
      (88%), secondary (10%) or tertiary (2%) discharge diagnosis were included. Data
      was collected nationwide from all 22 hospitals with a coronary angiolaboratory.
      RESULTS: The study period included 48,584 NSTEMI admissions of which 55.3% (95%
      confidence interval (CI) 54.6-56.0%) were of men and 44.7% (CI 44.1-45.3%) were
      of women, with age-adjusted relative risk of 1.86 (CI 1.60-2.16, p < 0.0001) for
      male gender. Female patients were significantly older than males (77.8 SD 10.2
      vs. 70.2 SD 11.9 years, p < 0.0001). Standardized incidence rate of NSTEMI was
      20.6 (CI 20.4-20.8)/10,000 person-years overall, 28.7 (CI 28.3-29.0)/10,000 in
      men and 15.0 (CI 14.7-15.2)/10,000 in women. Men had a 2.36-fold (CI 2.23-2.49; p
      < 0.0001) age-adjusted relative risk for NSTEMI compared with women, with highest
      risk difference in population under 40 years of age (relative risk 4.48; CI 3.10
      6.48, p < 0.0001). Incidence increased with age by an estimated gender-adjusted
      increase rate of 61% (CI 59-62%; p < 0.0001) per five-year increase in age.
      CONCLUSIONS: Men have a 2.4-fold overall risk for NSTEMI compared with women,
      with highest relative risk in young adults. Incidence rate of non-ST-elevation
      myocardial infarction increases by an estimated 61% per five-year increase in
      age.

PMID- 24914030
TI  - Domain-specific genetic influence on visual-ambiguity resolution.
AB  - The visual world is flooded with ambiguity. Generally, people can resolve the
      ambiguity almost instantaneously, as when they distinguish at a glance whether a
      maiden in a portrait by Picasso is in profile or facing front. However,
      perception of the same reality, though relatively stable at the individual level,
      can vary dramatically from person to person, manifesting idiosyncratic perceptual
      biases. What drives the heterogeneity of human vision as reflected in the
      resolution of visual ambiguity? Using the twin method, we demonstrated a
      significant genetic contribution to individual differences in the visual
      disambiguation of bistable biological-motion stimuli but not inanimate motion
      stimuli. These findings challenge the prevailing view that the way the human
      brain makes sense of visual input is largely shaped by a person's perceptual
      history. Rather, the visual perception of biologically salient information can be
      guided by adaptive mental "priors" that are genetically transmitted. 

PMID- 24914029
TI  - Secondary medical prevention and clinical outcome in coronary artery disease
      patients with a history of non-coronary vascular intervention: A report from the
      CORONOR investigators.
AB  - AIM: To assess the level of secondary prevention and the outcome of coronary
      artery disease (CAD) in patients who have a history of non-coronary vascular
      intervention. BACKGROUND: Patients with polyvascular disease have been reported
      to receive less evidence-based medications, with worse risk factor control and to
      be at higher risk than patients with single-bed disease. It is unknown whether
      these findings remain valid in the modern era of secondary prevention. METHODS:
      We included 4184 patients with stable CAD. Two groups were formed according to
      the absence (n = 3704) or presence (n = 480) of a history of non-coronary
      vascular intervention. Treatments and risk factor control were recorded at
      inclusion. Follow-up was performed after 2 years. RESULTS: Antiplatelets,
      angiotensin system antagonists, beta-blockers and statins were widely prescribed
      in both groups. The number of antihypertensive drugs was higher in patients with
      non-coronary vascular intervention. Except for slight increases in the rate of
      current smokers and in systolic blood pressure, risk factor control was similar
      between groups. All-cause and cardiovascular mortality rates were higher in
      patients with non-coronary intervention with adjusted HR of 1.55 (1.13-2.13) (p =
      0.007), and 1.98 (1.24-3.15) (p = 0.004), respectively. CONCLUSIONS: In modern
      practice and real life conditions, the higher risk of CAD patients with a history
      of non-coronary vascular intervention is taken into account, with more intense
      secondary prevention and similar risk factor control than patients without such
      history. In spite of the level of secondary prevention, patients with a history
      of non-coronary vascular intervention remain at high risk of cardiovascular
      events. This should be an incentive to discuss more stringent objectives for
      secondary prevention in patients with polyvascular disease.

PMID- 24914032
TI  - Return to Play After Partial Lateral Meniscectomy in National Football League
      Athletes.
AB  - BACKGROUND: Lateral meniscal injury is a common and possibly career-threatening
      injury among players in the National Football League (NFL). The rate of return to
      play (RTP) and factors that affect RTP after lateral meniscal injury in NFL
      players are currently not defined. PURPOSE: The aims of this study were to
      determine the rate of RTP to regular-season NFL game play of NFL players after
      arthroscopic partial lateral meniscectomy and to identify factors that can
      predict the ability to return to play. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Seventy-two patients undergoing 77 arthroscopic lateral
      partial meniscectomies were followed to determine the rate of RTP (defined as
      successful RTP in at least 1 regular-season NFL game after meniscectomy) and
      factors predicting players' ability to return to play. Perioperative variables
      were recorded using retrospective chart review. Players' heights and weights,
      dates of return, draft rounds, and counts of games, starts, and seasons both
      before and after meniscectomy were all collected from statistical databases
      maintained by the NFL. Chi-square and Student t tests were performed to assess
      differences among covariates with respect to an athlete's ability to return to
      play, and odds ratios were calculated as appropriate. All percentages were
      calculated as percent of total procedures performed (n = 77). RESULTS: Of the 77
      partial lateral meniscectomies performed, 61% (n = 47) resulted in the athlete
      returning to play at his previous level of competition with an average length of
      time to RTP of 8.5 months; 19 (40%) of those who returned were still active in
      the NFL at the time of follow-up. Age at time of surgery, games and seasons
      played before surgery, and individual position were not significantly different
      between those who did and did not return to play. Undergoing a concomitant
      procedure did not affect an athlete's ability to return to play, nor did
      concurrent arthroscopic anterior cruciate ligament reconstruction affect a
      player's likelihood to return to play. Players drafted in the first 4 rounds of
      the NFL draft were 3.7 times more likely to return to play than players drafted
      after the fourth round, and players who started more than 46.2% of their games
      played (the mean value for this population) were 2.8 times more likely to return
      to play. Speed-position players (running backs, receivers, linebackers, and
      defensive backs) were 4.0 times less likely to return to play than non-speed
      position players (linemen and tight ends). CONCLUSION: The majority of NFL
      players undergoing arthroscopic lateral meniscectomy are able to return to play.
      Players selected earlier in the NFL draft and who are listed as starters in more
      of their games are more likely to return to play, as are linemen and tight ends.
      It is significantly more difficult for running backs, receivers, linebackers, and
      defensive backs to return to play.

PMID- 24914031
TI  - Activity Tolerance After Periacetabular Osteotomy.
AB  - BACKGROUND: Periacetabular osteotomy is a well-described surgical intervention
      for symptomatic acetabular deformities in skeletally mature patients. Data
      regarding return to athletic activity or sport after this procedure are still
      limited. PURPOSE: To evaluate the ability of patients to return to preoperative
      levels of activity after periacetabular osteotomy. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: This is a retrospective review of active patients
      treated with periacetabular osteotomy for acetabular deformity correction.
      Patients were identified as those with preoperative University of California-Los
      Angeles activity levels >=7. Patient demographics, operative data, radiographic
      measures, and clinical outcomes were documented prospectively. The University of
      California-Los Angeles activity score, Harris Hip Score, Hip Dysfunction and
      Osteoarthritis Outcome Score, and Western Ontario and McMaster Universities
      Osteoarthritis Index were used to measure clinical outcomes, and details
      regarding activity and satisfaction were analyzed. RESULTS: This study included
      36 patients (39 hips; 15 males and 21 females) whose average age was 25 years
      (range, 15-45 years) and whose average body mass index was 24 +/- 3.5 kg/m(2).
      Mean follow-up was 33 months (range, 18-59 months). Preoperatively, the average
      lateral center edge angle, anterior center edge angle, and acetabular index were
      10 degrees , 14 degrees , and 21 degrees , respectively; 92% of patients had a
      Tonnis osteoarthritis grade of 0 or 1. One patient failed hip preservation
      surgery and went on to total hip arthroplasty 27 months after periacetabular
      osteotomy. Of the remaining patients, 71% reported an increase or no change in
      activity level postoperatively. The University of California-Los Angeles score
      was also unchanged (9.2 vs 8.8, P = .157), and the Harris Hip Score (63 vs 87, P
      < .001), Hip Dysfunction and Osteoarthritis Outcome Score-Quality of Life (38 vs
      71, P < .001), and Western Ontario and McMaster Universities Osteoarthritis Index
      (71 vs 92, P < .001) results improved from preoperative levels. There was a 97%
      rate of satisfaction with the surgery. Four patients (11%) reported hip pain as
      the primary factor limiting postoperative activity. CONCLUSION: The majority
      (71%) of active patients with hip dysplasia return to presurgical or higher
      activity levels after open hip preservation surgery with the periacetabular
      osteotomy.

PMID- 24914034
TI  - Application of good practices as described by the NEPSI agreement coincides with
      a strong decline in the exposure to respiratory crystalline silica in Finnish
      workplaces.
AB  - To protect the health of those occupationally exposed to respirable crystalline
      silica, the main industries in European Union associated with exposure to
      respirable silica, agreed on appropriate measures for the improvement of working
      conditions through the application of good practices, as part of 'The Agreement
      on Workers Health Protection through the Good Handling and Use of Crystalline
      Silica and Products Containing it' (NEPSI agreement), signed in April 2006. The
      present paper examines trends in exposure to respirable crystalline silica in
      Finland prior to and following the implementation of the NEPSI agreement and
      includes a working example of the NEPSI approach in the concrete industry. Data
      derived from workplace exposure assessments during the years 1994-2013 are
      presented, including 2556 air samples collected mostly indoors, from either the
      breathing zone of workers or from stationary points usually at a height of 1.5 m
      above the floor, with the aim to estimate average exposure of workers to
      respiratory crystalline silica during an 8-h working day. The aim was, to find
      out how effective this unique approach has been in the management of one of the
      major occupational hazards in the concerned industries. Application of good
      practices as described by the NEPSI agreement coincides with a strong decline in
      the exposure to respirable crystalline silica in Finnish workplaces, as
      represented by the clientele of Finnish Institute of Occupational Health. During
      the years followed in the present study, we see a >10-fold decrease in the
      average and median exposures to respirable silica. Prior to the implementation of
      the NEPSI agreement, >50% of the workplace measurements yielded results above the
      OEL8 h (0.2mg m(-3)). As of present (2013), circa 10% of the measurements are
      above of or identical to the OEL8 h (0.05mg m(-3)). 

PMID- 24914033
TI  - Ultrasonography as a useful modality for documenting sacroiliitis in
      radiographically negative inflammatory back pain: a comparative evaluation with
      MRI.
AB  - OBJECTIVES: The aims of this study were to identify and characterize features of
      sacroiliitis in patients with non-radiographic inflammatory low back pain by
      ultrasonography (USG) and to correlate the findings with that of MRI. METHODS:
      MRI and USG of SI joints were performed on 29 patients who fulfilled the
      definition of inflammatory low back pain according to the Assessment of
      SpondyloArthritis International Society 2009 criteria for axial SpA but were X
      ray negative for sacroiliitis. Increased vascularity, low resistive index (RI)
      and hyperechogenicity of the joint space were considered USG features of
      sacroiliitis. The findings were compared with those of 32 controls. USG features
      of sacroiliitis were compared with MRI by kappa statistics. RESULTS: Receiver
      operating characteristic analysis revealed cut-off values for flow signals and RI
      of 3 and 0.605, respectively. There was a significant difference in the number of
      flow signals, RI and echogenicity of the SI joint between MRI-proven cases and
      controls. The Cohen's kappa for flow signals, RI and hyperechogenicity when
      compared with MRI were 0.816 (95% CI 0.676, 0.937) and 0.821 (95% CI 0.662,
      0.965) and 0.403 (95% CI 0.108, 0.695). Taking both flow signals and RI
      parameters as criteria for determining sacroiliitis, comparison with MRI returned
      a kappa of 0.816 (95% CI 0.601, 0.963). CONCLUSION: Three or more flow signals
      and a RI <=0.605 can be applied as USG criteria for sacroiliitis. USG can be a
      cost-effective and non-inferior modality compared with MRI in documenting
      sacroiliitis in early SpA.

PMID- 24914035
TI  - Small RNA profiling and characterization of piRNA clusters in the adult testes of
      the common marmoset, a model primate.
AB  - Small RNAs mediate gene silencing by binding Argonaute/Piwi proteins to regulate
      target RNAs. Here, we describe small RNA profiling of the adult testes of
      Callithrix jacchus, the common marmoset. The most abundant class of small RNAs in
      the adult testis was piRNAs, although 353 novel miRNAs but few endo-siRNAs were
      also identified. MARWI, a marmoset homolog of mouse MIWI and a very abundant PIWI
      in adult testes, associates with piRNAs that show characteristics of mouse
      pachytene piRNAs. As in other mammals, most marmoset piRNAs are derived from
      conserved clustered regions in the genome, which are annotated as intergenic
      regions. However, unlike in mice, marmoset piRNA clusters are also found on the X
      chromosome, suggesting escape from meiotic sex chromosome inactivation by the X
      linked clusters. Some of the piRNA clusters identified contain antisense
      orientated pseudogenes, suggesting the possibility that pseudogene-derived piRNAs
      may regulate parental functional protein-coding genes. More piRNAs map to
      transposable element (TE) subfamilies when they have copies in piRNA clusters. In
      addition, the strand bias observed for piRNAs mapped to each TE subfamily
      correlates with the polarity of copies inserted in clusters. These findings
      suggest that pachytene piRNA clusters determine the abundance and strand-bias of
      TE-derived piRNAs, may regulate protein-coding genes via pseudogene-derived
      piRNAs, and may even play roles in meiosis in the adult marmoset testis. 

PMID- 24914036
TI  - Reduction of radiation to children: our responsibility to change.

PMID- 24914037
TI  - Cumulative radiation exposure and cancer risk estimation in children with heart
      disease.
AB  - BACKGROUND: Children with heart disease are frequently exposed to imaging
      examinations that use ionizing radiation. Although radiation exposure is
      potentially carcinogenic, there are limited data on cumulative exposure and the
      associated cancer risk. We evaluated the cumulative effective dose of radiation
      from all radiation examinations to estimate the lifetime attributable risk of
      cancer in children with heart disease. METHODS AND RESULTS: Children <=6 years of
      age who had previously undergone 1 of 7 primary surgical procedures for heart
      disease at a single institution between 2005 and 2010 were eligible for the
      study. Exposure to radiation-producing examinations was tabulated, and cumulative
      effective dose was calculated in millisieverts. These data were used to estimate
      lifetime attributable risk of cancer above baseline using the approach of the
      Committee on Biological Effects of Ionizing Radiation VII. The cohort included
      337 children exposed to 13 932 radiation examinations. Conventional radiographs
      represented 92% of examinations, whereas cardiac catheterization and computed
      tomography accounted for 81% of cumulative exposure. Overall median cumulative
      effective dose was 2.7 mSv (range, 0.1-76.9 mSv), and the associated lifetime
      attributable risk of cancer was 0.07% (range, 0.001%-6.5%). Median lifetime
      attributable risk of cancer ranged widely depending on surgical complexity
      (0.006%-1.6% for the 7 surgical cohorts) and was twice as high in females per
      unit exposure (0.04% versus 0.02% per 1-mSv effective dose for females versus
      males, respectively; P<0.001). CONCLUSIONS: Overall radiation exposures in
      children with heart disease are relatively low; however, select cohorts receive
      significant exposure. Cancer risk estimation highlights the need to limit
      radiation dose, particularly for high-exposure modalities.

PMID- 24914038
TI  - Compartmental modeling of whole-body vitamin A kinetics in unsupplemented and
      vitamin A-retinoic acid-supplemented neonatal rats.
AB  - Little is known about the contribution of different tissues to whole-body vitamin
      A (VA) kinetics in neonates. Here, we have used model-based compartmental
      analysis of tissue tracer kinetic data from unsupplemented (control) and VA
      retinoic acid (VARA)-supplemented neonatal rats to determine VA kinetics in
      specific tissues under control and supplemented conditions. First, compartmental
      models for retinol kinetics were developed for individual tissues, and then an
      integrated compartmental model incorporating all tissues was developed for both
      groups. The models predicted that 52% of chylomicron (CM) retinyl ester was
      cleared by liver in control pups versus 22% in VARA-treated pups, whereas about
      51% of VA was predicted to be extrahepatic in 4- to 6-day-old unsupplemented
      neonatal rats. VARA increased CM retinyl ester uptake by lung, carcass, and
      intestine; decreased the release into plasma of retinol that had been cleared by
      liver and lung as CM retinyl esters; stimulated the uptake of retinol from plasma
      holo-retinol binding protein into carcass; and decreased the retinol turnover out
      of the liver. Overall, neonatal VA trafficking differed from that previously
      described for adult animals, with a larger contribution of extrahepatic tissues
      to CM clearance, especially after VA supplementation, and a significant amount of
      VA distributed in extrahepatic tissues. 

PMID- 24914039
TI  - Exercise and the heart.

PMID- 24914043
TI  - In reply to Gandaglia et al.

PMID- 24914042
TI  - In reply to the letter to the editor 'in Reply to Gandaglia et al.' by De Bari et
      al.

PMID- 24914041
TI  - Adjuvant radiotherapy for extremity and trunk wall atypical lipomatous tumor/well
      differentiated LPS (ALT/WD-LPS): a French Sarcoma Group (GSF-GETO) study.
AB  - BACKGROUND: The role of adjuvant radiotherapy (RT) in the management of atypical
      lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains
      controversial. METHODS: Two hundred eighty-three patients with operable ALT/WD
      LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984
      and 2011 registered in the Conticabase database were included and described.
      Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR)
      were evaluated from the time of first treatment. RESULTS: Three of 20 centers
      enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years,
      147 patients (52%) were males, 222 (78%) patients had their primary tumor located
      in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and
      the trunk wall, respectively. The median size of primary tumors was 17 cm (range
      2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received
      adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs
      (P < 0.001). Use of adjuvant RT varied across centers and along the study period.
      Other characteristics were balanced between the two groups. Median follow-up was
      61.7 months. None of the patients developed metastasis during follow-up. The 5
      year local relapse-free survival rates were 98.3% versus 80.3% with and without
      adjuvant RT, respectively (P < 0.001). Once stratified on time period
      (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other)
      were independently associated with TTLR. No OS difference was observed (P =
      0.105). CONCLUSION: In this study, adjuvant RT following resection of ALT/WD-LPS
      was associated with a reduction of LR risk.

PMID- 24914040
TI  - Historical controls for metastatic pancreatic cancer: benchmarks for planning and
      analyzing single-arm phase II trials.
AB  - We compiled and analyzed a database of cooperative group trials in advanced
      pancreatic cancer to develop historical benchmarks for overall survival (OS) and
      progression-free survival (PFS). Such benchmarks are essential for evaluating new
      therapies in a single-arm setting. The analysis included patients with untreated
      metastatic pancreatic cancer receiving regimens that included gemcitabine,
      between 1995 and 2005. Prognostic baseline factors were selected by their
      significance in Cox regression analysis. Outlier trial arms were identified by
      comparing individual 6-month OS and PFS rates against the entire group. The
      dataset selected for the generation of OS and PFS benchmarks was then tested for
      intertrial arm variability using a logistic-normal model with the selected
      baseline prognostic factors as fixed effects and the individual trial arm as a
      random effect. A total of 1,132 cases from eight trials qualified. Performance
      status and sex were independently significant for OS, and performance status was
      prognostic for PFS. Outcomes for one trial (NCCTG-034A) were significantly
      different from the other trial arms. When this trial was excluded, the remaining
      trial arms were homogeneous for OS and PFS outcomes after adjusting for
      performance status and sex. Benchmark values for 6-month OS and PFS are reported
      along with a method for using these values in future study design and analysis.
      The benchmark survival values were generated from a dataset that was homogeneous
      between trials. The benchmarks can be used to enable single-arm phase II trials
      using a gemcitabine platform, especially under certain circumstances. Such
      circumstances might be when a randomized control arm is not practically feasible,
      an early signal of activity of an experimental agent is being explored such as in
      expansion cohorts of phase I studies, and in patients who are not candidates for
      combination cytotoxic therapy.

PMID- 24914044
TI  - A phase I/II study of lenalidomide in combination with sunitinib in patients with
      advanced or metastatic renal cell carcinoma.
AB  - BACKGROUND: This phase I/II study was conducted to determine the maximum
      tolerated dose (MTD), safety, and efficacy of lenalidomide plus sunitinib in
      metastatic renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: Patients
      with histologically confirmed, metastatic RCC were treated with 10 mg/day
      lenalidomide plus 37.5 mg/day sunitinib, orally in 21-day cycles. Doses were
      escalated to determine the MTD in phase I, with additional patients planned at
      this dose in phase II. Primary end points were MTD and response rate. RESULTS:
      Sixteen patients received a median of 2, 3, and 5 cycles in cohort 1
      [lenalidomide 10 mg (days 1-21) and sunitinib 37.5 mg (days 1-21)], cohort 2
      [lenalidomide 10 mg (days 1-21) and sunitinib 37.5 mg (days 1-14)], and cohort 3
      [lenalidomide 15 mg (days 1-21) and sunitinib 37.5 mg (days 1-14)], respectively.
      Median treatment durations were 41, 63, and 97 days for lenalidomide; and 41, 57,
      and 97.5 days for sunitinib. The MTD was found to be continuous dosing of
      lenalidomide 10 mg/day plus sunitinib 37.5 mg/day for 14 of 21 days. Dose
      limiting toxicities included neutropenia, leukopenia, thrombocytopenia, asthenia,
      atrial fibrillation, and increased transaminases. The most frequent grade 3-4
      treatment-emergent adverse events were hematologic, including neutropenia and
      leukopenia. One patient achieved partial response, and seven had stable disease
      of which three were confirmed at subsequent tumor assessments. B cells and
      several T-cell subsets were modulated versus baseline. CONCLUSION: The dose
      schedules of lenalidomide and sunitinib evaluated in this study were not well
      tolerated; cumulative toxicity precluded enrollment at the MTD.

PMID- 24914045
TI  - The new ACC/AHA cardiovascular risk guidelines: impact and controversies.

PMID- 24914046
TI  - Comprehensive mutational scanning of a kinase in vivo reveals substrate-dependent
      fitness landscapes.
AB  - Deep mutational scanning has emerged as a promising tool for mapping sequence
      activity relationships in proteins, ribonucleic acid and deoxyribonucleic acid.
      In this approach, diverse variants of a sequence of interest are first ranked
      according to their activities in a relevant assay, and this ranking is then used
      to infer the shape of the fitness landscape around the wild-type sequence. Little
      is currently known, however, about the degree to which such fitness landscapes
      are dependent on the specific assay conditions from which they are inferred. To
      explore this issue, we performed comprehensive single-substitution mutational
      scanning of APH(3')II, a Tn5 transposon-derived kinase that confers resistance to
      aminoglycoside antibiotics, in Escherichia coli under selection with each of six
      structurally diverse antibiotics at a range of inhibitory concentrations. We
      found that the resulting local fitness landscapes showed significant dependence
      on both antibiotic structure and concentration, and that this dependence can be
      exploited to guide protein engineering. Specifically, we found that differential
      analysis of fitness landscapes allowed us to generate synthetic APH(3')II
      variants with orthogonal substrate specificities. 

PMID- 24914047
TI  - Repetitive RNA unwinding by RNA helicase A facilitates RNA annealing.
AB  - Helicases contribute to diverse biological processes including replication,
      transcription and translation. Recent reports suggest that unwinding of some
      helicases display repetitive activity, yet the functional role of the
      repetitiveness requires further investigation. Using single-molecule fluorescence
      assays, we elucidated a unique unwinding mechanism of RNA helicase A (RHA) that
      entails discrete substeps consisting of binding, activation, unwinding, stalling
      and reactivation stages. This multi-step process is repeated many times by a
      single RHA molecule without dissociation, resulting in repetitive
      unwinding/rewinding cycles. Our kinetic and mutational analysis indicates that
      the two double stand RNA binding domains at the N-terminus of RHA are responsible
      for such repetitive unwinding behavior in addition to providing an increased
      binding affinity to RNA. Further, the repetitive unwinding induces an efficient
      annealing of a complementary RNA by making the unwound strand more accessible.
      The complex and unusual mechanism displayed by RHA may help in explaining how the
      repetitive unwinding of helicases contributes to their biological functions. 

PMID- 24914048
TI  - Jumonji domain containing protein 6 (Jmjd6) modulates splicing and specifically
      interacts with arginine-serine-rich (RS) domains of SR- and SR-like proteins.
AB  - The Fe(II) and 2-oxoglutarate dependent oxygenase Jmjd6 has been shown to
      hydroxylate lysine residues in the essential splice factor U2 auxiliary factor 65
      kDa subunit (U2AF65) and to act as a modulator of alternative splicing. We
      describe further evidence for the role of Jmjd6 in the regulation of pre-mRNA
      processing including interactions of Jmjd6 with multiple arginine-serine-rich
      (RS)-domains of SR- and SR-related proteins including U2AF65, Luc7-like protein 3
      (Luc7L3), SRSF11 and Acinus S', but not with the bona fide RS-domain of SRSF1.
      The identified Jmjd6 target proteins are involved in different mRNA processing
      steps and play roles in exon dependent alternative splicing and exon definition.
      Moreover, we show that Jmjd6 modifies splicing of a constitutive splice reporter,
      binds RNA derived from the reporter plasmid and punctually co-localises with
      nascent RNA. We propose that Jmjd6 exerts its splice modulatory function by
      interacting with specific SR-related proteins during splicing in a RNA dependent
      manner. 

PMID- 24914049
TI  - TtcA a new tRNA-thioltransferase with an Fe-S cluster.
AB  - TtcA catalyzes the post-transcriptional thiolation of cytosine 32 in some tRNAs.
      The enzyme from Escherichia coli was homologously overexpressed in E. coli. The
      purified enzyme is a dimer containing an iron-sulfur cluster and displays
      activity in in vitro assays. The type and properties of the cluster were
      investigated using a combination of UV-visible absorption, EPR and Mossbauer
      spectroscopy, as well as by site-directed mutagenesis. These studies demonstrated
      that the TtcA enzyme contains a redox-active and oxygen-sensitive [4Fe-4S]
      cluster, chelated by only three cysteine residues and absolutely essential for
      activity. TtcA is unique tRNA-thiolating enzyme using an iron-sulfur cluster for
      catalyzing a non-redox reaction. 

PMID- 24914050
TI  - Ultrasensitive isolation, identification and quantification of DNA-protein
      adducts by ELISA-based RADAR assay.
AB  - Enzymes that form transient DNA-protein covalent complexes are targets for
      several potent classes of drugs used to treat infectious disease and cancer,
      making it important to establish robust and rapid procedures for analysis of
      these complexes. We report a method for isolation of DNA-protein adducts and
      their identification and quantification, using techniques compatible with high
      throughput screening. This method is based on the RADAR assay for DNA adducts
      that we previously developed (Kiianitsa and Maizels (2013) A rapid and sensitive
      assay for DNA-protein covalent complexes in living cells. Nucleic Acids Res.,
      41:e104), but incorporates three key new steps of broad applicability. (i) Silica
      assisted ethanol/isopropanol precipitation ensures reproducible and efficient
      recovery of DNA and DNA-protein adducts at low centrifugal forces, enabling cell
      culture and DNA precipitation to be carried out in a single microtiter plate.
      (ii) Rigorous purification of DNA-protein adducts by a procedure that eliminates
      free proteins and free nucleic acids, generating samples suitable for detection
      of novel protein adducts (e.g. by mass spectroscopy). (iii) Identification and
      quantification of DNA-protein adducts by direct ELISA assay. The ELISA-based
      RADAR assay can detect Top1-DNA and Top2a-DNA adducts in human cells, and gyrase
      DNA adducts in Escherichia coli. This approach will be useful for discovery and
      characterization of new drugs to treat infectious disease and cancer, and for
      development of companion diagnostics assays for individualized medicine. 

PMID- 24914051
TI  - MicroRNA-382 induced by HIF-1alpha is an angiogenic miR targeting the tumor
      suppressor phosphatase and tensin homolog.
AB  - Recent studies have revealed that microRNAs (miRs) play important roles in the
      regulation of angiogenesis. In this study, we have characterized miR-382
      upregulation by hypoxia and the functional relevance of miR-382 in tumor
      angiogenesis. miRs induced by hypoxia in MKN1 human gastric cancer cells were
      investigated using miRNA microarrays. We selected miR-382 and found that the
      expression of miR-382 was regulated by HIF-1alpha. Conditioned media (CM) from
      MKN1 cells transfected with a miR-382 inhibitor (antagomiR-382) under hypoxic
      conditions significantly decreased vascular endothelial cell (EC) proliferation,
      migration and tube formation. Algorithmic programs (Target Scan, miRanda and
      cbio) predicted that phosphatase and tensin homolog (PTEN) is a target gene of
      miR-382. Deletion of miR382-binding sequences in the PTEN mRNA 3'-untranslated
      region (UTR) diminished the luciferase reporter activity. Subsequent study showed
      that the overexpression of miR-382 or antagomiR-382 down- or upregulated PTEN and
      its downstream target AKT/mTOR signaling pathway, indicating that PTEN is a
      functional target gene of miR-382. In addition, PTEN inhibited miR-382-induced in
      vitro and in vivo angiogenesis as well as VEGF secretion, and the inhibition of
      miR-382 expression reduced xenograft tumor growth and microvessel density in
      tumors. Taken together, these results suggest that miR-382 induced by hypoxia
      promotes angiogenesis and acts as an angiogenic oncogene by repressing PTEN. 

PMID- 24914052
TI  - Regulation of L1 expression and retrotransposition by melatonin and its receptor:
      implications for cancer risk associated with light exposure at night.
AB  - Expression of long interspersed element-1 (L1) is upregulated in many human
      malignancies. L1 can introduce genomic instability via insertional mutagenesis
      and DNA double-strand breaks, both of which may promote cancer. Light exposure at
      night, a recently recognized carcinogen, is associated with an increased risk of
      cancer in shift workers. We report that melatonin receptor 1 inhibits
      mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1
      protein. The addition of melatonin receptor antagonists abolishes the MT1 effect
      on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich,
      but not melatonin-poor, human blood collected at different times during the
      circadian cycle suppresses endogenous L1 mRNA during in situ perfusion of tissue
      isolated xenografts of human cancer. Supplementation of human blood with
      exogenous melatonin or melatonin receptor antagonist during the in situ perfusion
      establishes a receptor-mediated action of melatonin on L1 expression. Combined
      tissue culture and in vivo data support that environmental light exposure of the
      host regulates expression of L1 elements in tumors. Our data imply that light
      induced suppression of melatonin production in shift workers may increase L1
      induced genomic instability in their genomes and suggest a possible connection
      between L1 activity and increased incidence of cancer associated with circadian
      disruption. 

PMID- 24914053
TI  - Simultaneous non-contiguous deletions using large synthetic DNA and site-specific
      recombinases.
AB  - Toward achieving rapid and large scale genome modification directly in a target
      organism, we have developed a new genome engineering strategy that uses a
      combination of bioinformatics aided design, large synthetic DNA and site-specific
      recombinases. Using Cre recombinase we swapped a target 126-kb segment of the
      Escherichia coli genome with a 72-kb synthetic DNA cassette, thereby effectively
      eliminating over 54 kb of genomic DNA from three non-contiguous regions in a
      single recombination event. We observed complete replacement of the native
      sequence with the modified synthetic sequence through the action of the Cre
      recombinase and no competition from homologous recombination. Because of the
      versatility and high-efficiency of the Cre-lox system, this method can be used in
      any organism where this system is functional as well as adapted to use with other
      highly precise genome engineering systems. Compared to present-day iterative
      approaches in genome engineering, we anticipate this method will greatly speed up
      the creation of reduced, modularized and optimized genomes through the
      integration of deletion analyses data, transcriptomics, synthetic biology and
      site-specific recombination. 

PMID- 24914056
TI  - PET imaging of disease progression and treatment effects in the experimental
      autoimmune encephalomyelitis rat model.
AB  - The experimental autoimmune encephalomyelitis model is a model of multiple
      sclerosis that closely mimics the disease characteristics in humans. The main
      hallmarks of multiple sclerosis are neuroinflammation (microglia activation,
      monocyte invasion, and T-cell infiltration) and demyelination. PET imaging may be
      a useful noninvasive technique for monitoring disease progression and drug
      treatment efficacy in vivo. METHODS: Experimental autoimmune encephalomyelitis
      was induced by myelin-oligodendrocyte glycoprotein immunization in female Dark
      Agouti rats. Experimental autoimmune encephalomyelitis rats were imaged at
      baseline and at days 6, 11, 15, and 19 after immunization to monitor monocyte and
      microglia activation ((11)C-PK11195) and demyelination ((11)C-MeDAS) during
      normal disease progression and during treatment with dexamethasone. RESULTS:
      (11)C-PK11195 PET detected activation of microglia and monocytes in the brain
      stem and spinal cord during disease progression. The uptake of (11)C-PK11195 was
      elevated in dexamethasone-treated animals that had shown mild clinical symptoms
      that had resolved at the time of imaging. Demyelination was not detected by (11)C
      MeDAS PET, probably because of the small size of the lesions (average, 0.13 mm).
      CONCLUSION: PET imaging of neuroinflammation can be used to monitor disease
      progression and the consequences of treatment in the experimental autoimmune
      encephalomyelitis rat model. PET imaging was more sensitive than clinical
      symptoms for detecting inflammatory changes in the central nervous system.

PMID- 24914054
TI  - A DNA-binding-site landscape and regulatory network analysis for NAC
      transcription factors in Arabidopsis thaliana.
AB  - Target gene identification for transcription factors is a prerequisite for the
      systems wide understanding of organismal behaviour. NAM-ATAF1/2-CUC2 (NAC)
      transcription factors are amongst the largest transcription factor families in
      plants, yet limited data exist from unbiased approaches to resolve the DNA
      binding preferences of individual members. Here, we present a TF-target gene
      identification workflow based on the integration of novel protein binding
      microarray data with gene expression and multi-species promoter sequence
      conservation to identify the DNA-binding specificities and the gene regulatory
      networks of 12 NAC transcription factors. Our data offer specific single-base
      resolution fingerprints for most TFs studied and indicate that NAC DNA-binding
      specificities might be predicted from their DNA-binding domain's sequence. The
      developed methodology, including the application of complementary functional
      genomics filters, makes it possible to translate, for each TF, protein binding
      microarray data into a set of high-quality target genes. With this approach, we
      confirm NAC target genes reported from independent in vivo analyses. We emphasize
      that candidate target gene sets together with the workflow associated with
      functional modules offer a strong resource to unravel the regulatory potential of
      NAC genes and that this workflow could be used to study other families of
      transcription factors. 

PMID- 24914055
TI  - A genetic approach for analyzing the co-operative function of the tRNA mimicry
      complex, eRF1/eRF3, in translation termination on the ribosome.
AB  - During termination of translation in eukaryotes, a GTP-binding protein, eRF3,
      functions within a complex with the tRNA-mimicking protein, eRF1, to decode stop
      codons. It remains unclear how the tRNA-mimicking protein co-operates with the
      GTPase and with the functional sites on the ribosome. In order to elucidate the
      molecular characteristics of tRNA-mimicking proteins involved in stop codon
      decoding, we have devised a heterologous genetic system in Saccharomyces
      cerevisiae. We found that eRF3 from Pneumocystis carinii (Pc-eRF3) did not
      complement depletion of S. cerevisiae eRF3. The strength of Pc-eRF3 binding to Sc
      eRF1 depends on the GTP-binding domain, suggesting that defects of the GTPase
      switch in the heterologous complex causes the observed lethality. We isolated
      mutants of Pc-eRF3 and Sc-eRF1 that restore cell growth in the presence of Pc
      eRF3 as the sole source of eRF3. Mapping of these mutations onto the latest 3D
      complex structure revealed that they were located in the binding-interface region
      between eRF1 and eRF3, as well as in the ribosomal functional sites.
      Intriguingly, a novel functional site was revealed adjacent to the decoding site
      of eRF1, on the tip domain that mimics the tRNA anticodon loop. This novel domain
      likely participates in codon recognition, coupled with the GTPase function. 

PMID- 24914057
TI  - Regulatory Requirements for PET Drug Production.
AB  - The Food and Drug Administration (FDA) issued the final rule for title 21 of Code
      of Federal Regulations part 212 regarding the regulations on current good
      manufacturing practice for PET drugs. The regulations are intended to ensure that
      PET drugs meet the safety and quality assurance requirements of the Federal Food,
      Drug, and Cosmetic Act. The new regulation became effective December 12, 2011,
      but the FDA used regulatory discretion to allow new drug applications and
      abbreviated new drug applications to be filed until June 12, 2012, without
      interruption of the existing PET drug production for human use. The production of
      PET drugs for both clinical use and clinical research use are outlined in this
      continuing education module, including an overview of specific requirements for
      compliance. Additionally, FDA preapproval inspections and postapproval reporting
      requirements are reviewed.

PMID- 24914058
TI  - Image-derived input function from the vena cava for 18F-FDG PET studies in rats
      and mice.
AB  - Measurement of arterial input function is a restrictive aspect for quantitative
      (18)F-FDG PET studies in rodents because of their small total blood volume and
      the related difficulties in withdrawing blood. METHODS: In the present study, we
      took advantage of the high spatial resolution of a recent dedicated small-animal
      scanner to extract the input function from the (18)F-FDG PET images in Sprague
      Dawley rats (n = 4) and C57BL/6 mice (n = 5), using the vena cava. In the rat
      experiments, the validation of the image-derived input function (IDIF) method was
      made using an external microvolumetric blood counter as reference for the
      determination of the arterial input function, the measurement of which was
      confirmed by additional manually obtained blood samples. Correction for tracer
      bolus dispersion in blood between the vena cava and the arterial tree was
      applied. In addition, simulation studies were undertaken to probe the impact of
      the different IDIF extraction approaches on the determined cerebral metabolic
      rate of glucose (CMRGlc). In the mice measurements, the IDIF was used to compute
      the CMRGlc, which was compared with previously reported values, using the Patlak
      approach. RESULTS: The presented IDIF from the vena cava showed a robust
      determination of CMRGlc using either the compartmental modeling or the Patlak
      approach, even without bolus dispersion correction or blood sampling, with an
      underestimation of CMRGlc of 7% +/- 16% as compared with the reference data.
      Using this approach in the mice experiments, we measured a cerebral metabolic
      rate in the cortex of 0.22 +/- 0.10 MUmol/g/min (mean +/- SD), in good agreement
      with previous (18)F-FDG studies in the mouse brain. In the rat experiments,
      dispersion correction of the IDIF and additional scaling of the IDIF using a
      single manual blood sample enabled an optimized determination of CMRGlc, with an
      underestimation of 6% +/- 7%. CONCLUSION: The vena cava time-activity curve is
      therefore a minimally invasive alternative for the measurement of the (18)F-FDG
      input function in rats and mice, without the complications associated with
      repetitive blood sampling.

PMID- 24914059
TI  - The move from accuracy studies to randomized trials in PET: current status and
      future directions.
AB  - Since the influential study by van Tinteren et al. published in The Lancet in
      2002, there have been an increasing number of diagnostic randomized controlled
      trials (RCTs) investigating the benefit of PET. If they provide valid and useful
      information on the benefit, these studies can play an important role in informing
      guideline developers and policy makers. Our aim was to investigate how far the
      nuclear medicine community has come on its way from accuracy studies to RCTs and
      which issues we have to take into account in planning future studies. METHODS: We
      conducted a systematic review of diagnostic randomized trials, in which PET was
      applied in only one arm. We covered published studies as well as registered
      unpublished and planned studies. We considered 3 quality indicators related to
      the usefulness of a trial to generate evidence for a clinical benefit: use of
      patient-important outcome, sufficient sample size, and current standard as
      comparator. RESULTS: Fourteen published and 15 planned studies were identified.
      Five of the published studies and 12 of the planned studies did not use a patient
      important outcome. Sample sizes were often so small that a significant result
      could be expected only under the assumption of a substantial reduction in the
      event rate. Comparators typically reflected the current standard. CONCLUSION: If
      we consider the traditional areas of primary diagnosis, staging, and follow-up,
      then the number and quality of RCTs on PET is currently not sufficient to provide
      a major source for evidence-based decisions on the clinical benefit of PET. There
      will also be a future need in these traditional areas to deduce the clinical
      benefit of PET from the results of accuracy studies. The situation may be more
      favorable for the areas of treatment planning and response evaluation. Choice of
      patient-important outcomes and sufficient sample sizes are crucial issues in
      planning RCTs to demonstrate the clinical benefit of using PET.

PMID- 24914063
TI  - A computational theory of da Vinci stereopsis.
AB  - In binocular vision, occlusion of one object by another gives rise to monocular
      occlusions-regions visible only in one eye. Although binocular disparities cannot
      be computed for these regions, monocular occlusions can be precisely localized in
      depth and can induce the perception of illusory occluding surfaces. The
      phenomenon of depth perception from monocular occlusions, known as da Vinci
      stereopsis, is intriguing, but its mechanisms are not well understood. We first
      propose a theory of the mechanisms underlying da Vinci stereopsis that is based
      on the psychophysical and computational literature on monocular occlusions. It
      postulates, among other principles, that monocular areas are detected explicitly,
      and depth from occlusions is calculated based on constraints imposed by occlusion
      geometry. Next, we describe a biologically inspired computational model based on
      this theory that successfully reconstructs depth in a large range of stimuli and
      produces results similar to those described in the psychophysical literature.
      These results demonstrate that the proposed neural architecture could underpin da
      Vinci stereopsis and other stereoscopic percepts.

PMID- 24914061
TI  - Prognosis after a first hospitalisation for acute myocardial infarction and
      congestive heart failure by country of birth.
AB  - OBJECTIVE: To investigate differences in 28-day and 5-year mortality and 5-year
      readmission after a first hospitalisation for acute myocardial infarction (AMI)
      and congestive heart failure (CHF) between first generation ethnic minority
      groups (henceforth, migrants) and the ethnic Dutch population. METHODS:
      Nationwide prospective cohorts of first hospitalised AMI (N=213 630) and CHF
      patients (N=189 069) between 1998 and 2010 were built. Differences in 28-day and
      5-year mortality and in 5-year AMI/CHF readmission between migrants (Surinamese,
      Moroccan, Turkish, Antillean, Indonesian, Chinese and South Asian) and the ethnic
      Dutch population were investigated using Cox proportional hazard regression
      models. RESULTS: After the first AMI hospitalisation, mortality and AMI/CHF
      readmission were higher in the majority of migrant groups compared with ethnic
      Dutch. For example, HRs (adjusted for age, sex, marital status, degree of
      urbanisation and year of event) with 95% CIs among Surinamese (mainly of African
      or South-Asian origin) were 1.16 (1.02 to 1.32) for 28-day mortality, 1.44 (1.30
      to 1.60) for 5-year mortality, 1.33 (1.08 to 1.63) for AMI readmission and 2.09
      (1.82 to 2.40) for CHF readmission. After a first CHF hospitalisation, mortality
      rates among migrants were more diverse, with lower 28-day mortality among
      Moroccan and Turkish migrants and higher 5-year mortality among Surinamese,
      Chinese and South Asians. Readmission after CHF was often higher among migrant
      groups. CONCLUSIONS: Prognosis after a first AMI hospitalisation was worse among
      most migrant groups compared with the ethnic Dutch population. Ethnic
      inequalities in prognosis after a first CHF hospitalisation were more diverse.
      Efforts should be made to disentangle the underlying factors of the results.

PMID- 24914062
TI  - Relationships between sex, early valve surgery and mortality in patients with
      left-sided infective endocarditis analysed in a population-based cohort study.
AB  - OBJECTIVE: Whether sex-related differences in the prognosis of infective
      endocarditis (IE) are due to differences in disease severity or comorbid
      patterns, physiological specificities or a treatment indication bias is unclear.
      We conducted an analysis of the pooled database of two population-based cohorts
      of IE to reassess the relationships between sex, early valve surgery (EVS) and
      outcome in patients with IE. METHODS: Demographic and baseline characteristics,
      complications and outcome were compared in men and women with Duke-definite left
      sided IE. A propensity model for EVS was constructed using multivariate logistic
      regression. Factors associated with 1-year mortality were identified using
      multivariate Cox models adjusted for EVS factors. RESULTS: The study population
      included 466 (75%) men and 154 (25%) women. Compared with men, women were older
      (p=0.005), were more often on haemodialysis (p=0.04), more often had a mitral
      valve IE (50.0% vs 35.8%, p=0.02), less often developed a septic shock (p=0.05),
      less often underwent EVS (p=0.001) yet had comparable inhospital mortality rates
      (20.1% vs 20.0%, p=0.96) and similar 1-year survival probability (logrank
      p=0.68). Female sex was neither associated with EVS (OR 0.76 (95% CI 0.49 to
      1.16)) nor mortality (HR 1.17 (95% CI 0.80 to 1.69)). However EVS was associated
      with an increased risk of death in women in the early postoperative period (HR
      8.72 (95% CI 3.42 to 22.24), p=<0.0001). CONCLUSIONS: Women underwent EVS less
      often than men. However female sex was independently associated with neither EVS
      nor 1-year mortality. The reasons for a higher risk of early postoperative
      mortality in women must still be elucidated.

PMID- 24914060
TI  - Prescription of secondary prevention medications, lifestyle advice, and referral
      to rehabilitation among acute coronary syndrome inpatients: results from a large
      prospective audit in Australia and New Zealand.
AB  - OBJECTIVE: To evaluate the proportion of patients hospitalised with acute
      coronary syndrome (ACS) in Australia and New Zealand who received optimal
      inpatient preventive care and to identify factors associated with preventive
      care. METHODS: All patients hospitalised bi-nationally with ACS were identified
      between 14-27 May 2012. Optimal in-hospital preventive care was defined as having
      received lifestyle advice, referral to rehabilitation, and prescription of
      secondary prevention pharmacotherapies. Multilevel multivariable logistic
      regression was used to determine factors associated with receipt of optimal
      preventive care. RESULTS: For the 2299 ACS survivors, mean (SD) age was 69 (13)
      years, 46% were referred to rehabilitation, 65% were discharged on sufficient
      preventive medications, and 27% received optimal preventive care. Diagnosis of ST
      elevation myocardial infarction (OR: 2.64 [95% CI: 1.88-3.71]; p<0.001) and non
      ST elevation myocardial infarction (OR: 1.99 [95% CI: 1.52-2.61]; p<0.001)
      compared with a diagnosis of unstable angina, having a percutaneous coronary
      intervention (PCI) (OR: 4.71 [95% CI: 3.67-6.11]; p<0.001) or coronary bypass
      (OR: 2.10 [95% CI: 1.21-3.60]; p=0.011) during the admission or history of
      hypertension (OR:1.36 [95% CI: 1.06-1.75]; p=0.017) were associated with greater
      exposure to preventive care. Age over 70 years (OR:0.53 [95% CI: 0.35-0.79];
      p=0.002) or admission to a private hospital (OR:0.59 [95% CI: 0.42-0.84];
      p=0.003) were associated with lower exposure to preventive care. CONCLUSIONS:
      Only one-quarter of ACS patients received optimal secondary prevention in
      hospital. Patients with UA, who did not have PCI, were over 70 years or were
      admitted to a private hospital, were less likely to receive optimal care.

PMID- 24914064
TI  - Bluetongue virus without NS3/NS3a expression is not virulent and protects against
      virulent bluetongue virus challenge.
AB  - Bluetongue is a disease in ruminants caused by the bluetongue virus (BTV), and is
      spread by Culicoides biting midges. Bluetongue outbreaks cause huge economic
      losses and death in sheep in several parts of the world. The most effective
      measure to control BTV is vaccination. However, both commercially available
      vaccines and recently developed vaccine candidates have several shortcomings.
      Therefore, we generated and tested next-generation vaccines for bluetongue based
      on the backbone of a laboratory-adapted strain of BTV-1, avirulent BTV-6 or
      virulent BTV-8. All vaccine candidates were serotyped with VP2 of BTV-8 and did
      not express NS3/NS3a non-structural proteins, due to induced deletions in the
      NS3/NS3a ORF. Sheep were vaccinated once with one of these vaccine candidates and
      were challenged with virulent BTV-8 3 weeks after vaccination. The NS3/NS3a
      knockout mutation caused complete avirulence for all three BTV backbones,
      including for virulent BTV-8, indicating that safety is associated with the
      NS3/NS3a knockout phenotype. Viraemia of vaccine virus was not detected using
      sensitive PCR diagnostics. Apparently, the vaccine viruses replicated only
      locally, which will minimize spread by the insect vector. In particular, the
      vaccine based on the BTV-6 backbone protected against disease and prevented
      viraemia of challenge virus, showing the efficacy of this vaccine candidate. The
      lack of NS3/NS3a expression potentially enables the differentiation of infected
      from vaccinated animals, which is important for monitoring virus spread in
      vaccinated livestock. The disabled infectious single-animal vaccine for
      bluetongue presented here is very promising and will be the subject of future
      studies.

PMID- 24914065
TI  - Dating the origin of the genus Flavivirus in the light of Beringian biogeography.
AB  - The genus Flavivirus includes some of the most important human viral pathogens,
      and its members are found in all parts of the populated world. The temporal
      origin of diversification of the genus has long been debated due to the inherent
      problems with dating deep RNA virus evolution. A generally accepted hypothesis
      suggests that Flavivirus emerged within the last 10 000 years. However, it has
      been argued that the tick-borne Powassan flavivirus was introduced into North
      America some time between the opening and closing of the Beringian land bridge
      that connected Asia and North America 15 000-11 000 years ago, indicating an even
      older origin for Flavivirus. To determine the temporal origin of Flavivirus, we
      performed Bayesian relaxed molecular clock dating on a dataset with high coverage
      of the presently available Flavivirus diversity by combining tip date
      calibrations and internal node calibration, based on the Powassan virus and
      Beringian land bridge biogeographical event. Our analysis suggested that
      Flavivirus originated ~85 000 (64 000-110 000) or 120 000 (87 000-159 000) years
      ago, depending on the circumscription of the genus. This is significantly older
      than estimated previously. In light of our results, we propose that it is likely
      that modern humans came in contact with several members of the genus Flavivirus
      much earlier than suggested previously, and that it is possible that the spread
      of several flaviviruses coincided with, and was facilitated by, the migration and
      population expansion of modern humans out of Africa.

PMID- 24914066
TI  - Characterization of recombinant influenza A virus as a vector expressing
      respiratory syncytial virus fusion protein epitopes.
AB  - Respiratory syncytial virus (RSV) is the most common cause of respiratory
      infection in infants and the elderly, and no vaccine against this virus has yet
      been licensed. Here, we report a recombinant PR8 influenza virus with the RSV
      fusion (F) protein epitopes of the subgroup A gene inserted into the influenza
      virus non-structural (NS) gene (rFlu/RSV/F) that was generated as an RSV vaccine
      candidate. The rescued viruses were assessed by microscopy and Western blotting.
      The proper expression of NS1, the NS gene product, and the nuclear export protein
      (NEP) of rFlu/RSV/F was also investigated using an immunofluorescent assay. The
      rescued virus replicated well in the MDCK kidney cell line, A549 lung
      adenocarcinoma cell line and CNE-2Z nasopharyngeal carcinoma cell line. BALB/c
      mice immunized intranasally with rFlu/RSV/F had specific haemagglutination
      inhibition antibody responses against the PR8 influenza virus and RSV
      neutralization test proteins. Furthermore, intranasal immunization with
      rFlu/RSV/F elicited T helper type 1-dominant cytokine profiles against the RSV
      strain A2 virus. Taken together, our findings suggested that rFlu/RSV/F was
      immunogenic in vivo and warrants further development as a promising candidate
      vaccine.

PMID- 24914069
TI  - A poorly neutralizing IgG2a/c response elicited by a DNA vaccine protects mice
      against Japanese encephalitis virus.
AB  - We demonstrated previously that immunization with a DNA vaccine expressing the
      Japanese encephalitis virus (JEV) envelope (E) protein conferred a high level of
      protection through a poorly neutralizing antibody response. Here, we further
      investigated the role of the IgG subclass in this antibody-dependent protection
      using cytokine co-immunization and cytokine-deficient mice. A significant
      difference in IgG2a/c but not IgG1 was observed between mice that survived or
      died following a lethal challenge. Correspondingly, the IgG2a/c response and
      protection increased in IL-4-deficient mice but decreased in IFN-gamma-deficient
      mice, highlighting the importance of IgG2a/c. In addition, the restoration of
      protection and E-specific IgG2a/c production in IFN-gamma-deficient mice by a T
      helper (Th) type 1-biased intramuscular immunization suggested that IgG2a/c but
      not IFN-gamma was the major component for protection. The failure of protection
      against a direct intracranial challenge indicated that IgG2a/c-mediated
      protection was restricted to outside the central nervous system. Consistent with
      this conclusion, passive transfer of E-specific antisera conferred protection
      only pre-exposure to JEV. Therefore, our data provided evidence that the IgG
      subclass plays an important role in protection against JEV, particular in poorly
      neutralizing E-specific antibodies, and Th1-biased IgG2a/c confers better
      protection than Th2-biased IgG1 against JEV.

PMID- 24914068
TI  - Evolutionary genetics of genotype H1 measles viruses in China from 1993 to 2012.
AB  - Virologic surveillance is a critical component of measles management. One of the
      criteria for verification of elimination of endemic measles is genetic analysis
      of wild-type viruses to demonstrate lack of an indigenous genotype. Measles is
      yet to be eliminated in China, and genotype H1 has been detected continuously
      since virologic surveillance was initiated in 1993. Virologic surveillance has
      been very active in China, providing a unique opportunity to conduct a detailed
      study of the evolution of a single, endemic genotype over a timespan of nearly
      two decades. Phylogenetic analysis performed on the 450 nt coding sequence for
      the C-terminal 150 amino acids of the nucleoprotein (N-450), fusion (F) gene and
      haemagglutinin (H) gene confirmed the continued circulation of genotype H1
      viruses for 19 years. No evidence of selective pressure for the H protein was
      found. The substitution rates ranged from 0.75*10(-3) substitutions site(-1)
      year(-1) for H to 1.65*10(-3) substitutions site(-1) year(-1) for N-450. The time
      of most recent common ancestor (TMRCA) for genotype H1 was estimated as
      approximately 1985 (95 % highest probability density, 1979-1989). Finally, the
      overall diversity of measles sequences from China decreased from 2005 to 2012,
      coincident with a substantial decrease in measles cases. The results suggest that
      detailed evolutionary analyses should facilitate the documentation of eventual
      measles elimination in China. Moreover, the molecular approaches used in this
      study can be applied in other countries approaching measles elimination.

PMID- 24914067
TI  - Vaccinia virus virulence factor N1 can be ubiquitylated on multiple lysine
      residues.
AB  - Ubiquitylation is a covalent post-translational modification that regulates
      protein stability and is involved in many biological functions. Proteins may be
      modified with mono-ubiquitin or ubiquitin chains. Viruses have evolved multiple
      mechanisms to perturb the cell ubiquitin system and manipulate it to their own
      benefit. Here, we report ubiquitylation of vaccinia virus (VACV) protein N1. N1
      is an inhibitor of the nuclear factor NF-kappaB and apoptosis that contributes to
      virulence, has a Bcl-2-like fold, and is highly conserved amongst
      orthopoxviruses. The interaction between N1 and ubiquitin occurs at endogenous
      protein levels during VACV infection and following ectopic expression of N1.
      Biochemical analysis demonstrated that N1 is covalently ubiquitylated, and
      heterodimers of ubiquitylated and non-ubiquitylated N1 monomers were identified,
      suggesting that ubiquitylation does not inhibit N1 dimerization. Studies with
      other VACV Bcl-2 proteins, such as C6 or B14, revealed that although these
      proteins also interact with ubiquitin, these interactions are non-covalent.
      Finally, mutagenesis of N1 showed that ubiquitylation occurs in a conventional
      lysine-dependent manner at multiple acceptor sites because only an N1 allele
      devoid of lysine residues remained unmodified. Taken together, we described a
      previously uncharacterized modification of the VACV protein N1 that provided a
      new layer of complexity to the biology of this virulence factor, and provided
      another example of the intricate interplay between poxviruses and the host
      ubiquitin system.

PMID- 24914070
TI  - Response to H Zeidler's comments on the CONCERTO study.

PMID- 24914074
TI  - Comparison of different intubation techniques performed inside a moving
      ambulance: a manikin study.
AB  - OBJECTIVE. Airway management and endotracheal intubation may be required urgently
      when a patient deteriorates in an ambulance or aircraft during interhospital
      transfer or in a prehospital setting. The objectives of this study were: (1) to
      compare the effectiveness of conventional intubation by Macintosh laryngoscope in
      a moving ambulance versus that in a static ambulance; and (2) to compare the
      effectiveness of inverse intubation and GlideScope laryngoscopy with conventional
      intubation inside a moving ambulance. DESIGN. Comparative experimental study.
      SETTING. The experiment was conducted in an ambulance provided by the Auxiliary
      Medical Service in Hong Kong. PARTICIPANTS. A group of 22 doctors performed
      endotracheal intubation on manikins with Macintosh laryngoscope in a static and
      moving ambulance. In addition, they performed conventional Macintosh intubation,
      inverse intubation with Macintosh laryngoscope, and GlideScope intubation in a
      moving ambulance in both normal and simulated difficult airways. MAIN OUTCOME
      MEASURES. The primary outcome was the rate of successful intubation. The
      secondary outcomes were time taken for intubation, subjective glottis
      visualisation grading, and eventful intubation (oesophageal intubation,
      intubation time >60 seconds, and incisor breakage) with different techniques or
      devices. RESULTS. In normal airways, conventional Macintosh intubation in a
      static ambulance (95.5%), conventional intubation in a moving ambulance (95.5%),
      as well as GlideScope intubation in a moving ambulance (95.5%) were associated
      with high success rates; the success rate of inverse intubation was comparatively
      low (54.5%; P=0.004). In difficult airways, conventional Macintosh intubation in
      a static ambulance (86.4%), conventional intubation in a moving ambulance
      (90.9%), and GlideScope intubation in a moving ambulance (100%) were associated
      with high success rates; the success rate of inverse intubation was comparatively
      lower (40.9%; P=0.034). CONCLUSIONS. En-route intubation in an ambulance by
      conventional Macintosh laryngoscopy is superior to inverse intubation unless the
      cephalad access is impossible. GlideScope laryngoscopy appears to be associated
      with lower rates of eventful intubation in difficult airways and has better
      laryngoscopic view versus inverse intubation. 

PMID- 24914078
TI  - Acute appendicitis complicating Amyand's hernia: imaging features and literature
      review.
AB  - Acute appendicitis complicating Amyand's hernia is an extremely rare condition,
      in which the appendix herniates into the inguinal sac and, subsequently, gets
      inflamed. The condition is difficult to diagnose clinically. Imaging is valuable
      for its diagnosis and detection of the associated complications. In this article,
      we will discuss the imaging features of acute appendicitis complicating Amyand's
      hernia and the results of a literature review on the condition. 

PMID- 24914071
TI  - Reflecting on the global burden of musculoskeletal conditions: lessons learnt
      from the global burden of disease 2010 study and the next steps forward.
AB  - The objective of this paper is to provide an overview of the strengths,
      limitations and lessons learned from estimating the burden from musculoskeletal
      (MSK) conditions in the Global Burden of Disease 2010 Study (GBD 2010 Study). It
      should be read in conjunction with the other GBD 2010 Study papers published in
      this journal. The strengths of the GBD 2010 Study include: the involvement of a
      MSK expert group; development of new and more valid case definitions, functional
      health states, and disability weights to better reflect the MSK conditions; the
      extensive series of systematic reviews undertaken to obtain data to derive the
      burden estimates; and the use of a new, more advanced version of the disease
      modelling software (DisMod-MR). Limitations include: many regions of the world
      did not have data; the extent of heterogeneity between included studies; and
      burden does not include broader aspects of life, such as participation and well
      being. A number of lessons were learned. Ongoing involvement of experts is
      critical to ensure the success of future efforts to quantify and monitor this
      burden. A paradigm shift is urgently needed among global agencies in order to
      alleviate the rapidly increasing global burden from MSK conditions. Prevention
      and control of MSK disability are required, along with health system changes.
      Further research is needed to improve understanding of the predictors and
      clinical course across different settings, and the ways in which MSK conditions
      can be better managed and prevented.

PMID- 24914079
TI  - A novel mutation in pseudohypoparathyroidism type 1a in a Chinese woman and her
      son with hypocalcaemia.
AB  - Pseudohypoparathyroidism is a rare genetic disorder characterised by end-organ
      resistance to parathyroid hormone due to a defect of the guanine nucleotide
      binding protein alpha that simulates activity of the polypeptide 1 (GNAS) gene.
      Patients with type 1a pseudohypoparathyroidism display different features of
      Albright's hereditary osteodystrophy as well as multi-hormone resistance. We
      describe a Chinese woman and her son, who presented with different symptoms of
      pseudohypoparathyroidism and clinically manifested different degree of Albright's
      hereditary osteodystrophy. Genetic study detected a mutation
      [NM_000516.4(GNAS):c682C>T (p.Arg228Cys)] in the GNAS gene. 

PMID- 24914073
TI  - Obstructive sleep apnoea syndrome in patients with primary open-angle glaucoma.
AB  - OBJECTIVE: To investigate the prevalence of obstructive sleep apnoea syndrome in
      patients with primary open-angle glaucoma. DESIGN: Case series. SETTING: School
      of Medicine, Duzce University, Turkey. PATIENTS: Twenty-one consecutive primary
      open-angle glaucoma patients (12 females and 9 males) who attended the out
      patient clinic of the Department of Ophthalmology between July 2007 and February
      2008 were included in this study. All patients underwent polysomnographic
      examination. RESULTS: The prevalence of obstructive sleep apnoea syndrome was
      33.3% in patients with primary open-angle glaucoma; the severity of the condition
      was mild in 14.3% and moderate in 19.0% of the subjects. The age (P=0.047) and
      neck circumference (P=0.024) in patients with obstructive sleep apnoea syndrome
      were significantly greater than those without the syndrome. Triceps skinfold
      thickness in glaucomatous obstructive sleep apnoea syndrome patients reached near
      significance versus those without the syndrome (P=0.078). Snoring was observed in
      all glaucoma cases with obstructive sleep apnoea syndrome. The intra-ocular
      pressure of patients with primary open-angle glaucoma with obstructive sleep
      apnoea syndrome was significantly lower than those without obstructive sleep
      apnoea syndrome (P=0.006 and P=0.035 for the right and left eyes, respectively).
      There was no significant difference in the cup/disc ratio and visual acuity,
      except visual field defect, between primary open-angle glaucoma patients with and
      without obstructive sleep apnoea syndrome. CONCLUSIONS: Although it does not
      provide evidence for a cause-effect relationship, high prevalence of obstructive
      sleep apnoea syndrome in patients with primary open-angle glaucoma in this study
      suggests the need to explore the long-term results of coincidence, relationship,
      and cross-interaction of these two common disorders.

PMID- 24914075
TI  - An update on irreversible electroporation of liver tumours.
AB  - OBJECTIVE. To investigate the clinical efficacy and safety of irreversible
      electroporation for ablation of liver tumour in humans. DATA SOURCES. The PubMed
      and MEDLINE databases were systematically searched. STUDY SELECTION. Clinical
      research published in English in the last 10 years until October 2013 that
      address clinical issues related to irreversible electroporation of human liver
      tumours were selected. "Liver tumor", "local ablative therapy", and "irreversible
      electroporation" were used as the search terms. DATA EXTRACTION AND SYNTHESIS.
      The data extracted for this review was analysed by the authors, with a focus on
      the clinical efficacy and the safety of irreversible electroporation. The
      complete response rates look promising, ranging from 72% to 100%, except in one
      study in a subgroup of liver tumours in which the complete response rate was only
      50% that was likely due to the inclusion of larger-size tumours. In one study,
      the local recurrence rate at 12 months was approximately 40%. As for the safety
      of irreversible electroporation, there were only a few reported complications
      (cardiac arrhythmia, pneumothorax, and electrolyte disturbance) that were mostly
      transient and not serious. There was no reported mortality related to the use of
      irreversible electroporation. CONCLUSION. Irreversible electroporation is a
      potentially effective liver tumour ablative therapy that gives rise to only mild
      and transient side-effects. Further studies with better patient selection
      criteria and longer follow-up are needed to clarify its role as a first-line
      liver tumour treatment modality. 

PMID- 24914077
TI  - Live birth following double-factor pre-implantation genetic diagnosis for both
      reciprocal translocation and alpha-thalassaemia.
AB  - We report a live birth from a couple with two genetic diseases, namely:
      reciprocal translocation carrier and alpha-thalassaemia trait, following pre
      implantation genetic diagnostic tests. This is the first case in Hong Kong in
      which the technique of using one blastomere biopsy for two diseases was
      established, using array comparative genomic hybridisation and polymerase chain
      reaction. 

PMID- 24914080
TI  - Three different ophthalmic presentations of juvenile xanthogranuloma.
AB  - Three cases of juvenile xanthogranuloma from two ophthalmology departments were
      reviewed. Clinical histories, ophthalmic examination, physical examination,
      investigations, and treatment of these cases are described. A 4-month-old boy
      presented with spontaneous hyphema and secondary glaucoma. He was treated with
      intensive topical steroid and anti-glaucomatous eye drops. The hyphema gradually
      resolved and the intra-ocular pressure reverted to 11 mm Hg without any other
      medication. Biopsy of his scalp mass confirmed the diagnosis of juvenile
      xanthogranuloma. A 31-month-old boy presented with a limbal mass. Excisional
      biopsy of the mass was performed and confirmed it was a juvenile xanthogranuloma.
      A 20-month-old boy was regularly followed up for epiblepharon and astigmatism. He
      presented to a paediatrician with a skin nodule over his back. Skin biopsy
      confirmed juvenile xanthogranuloma. He had no other ocular signs. Presentation of
      juvenile xanthogranuloma can be very different, about which ophthalmologists
      should be aware of. Biopsy of the suspected lesion is essential to confirm the
      diagnosis. 

PMID- 24914076
TI  - Comparison is beyond IPASS and OPTIMAL.

PMID- 24914081
TI  - More than skin deep: Paget's disease of the perineum.

PMID- 24914082
TI  - Fever with vesicular rash in an adult.

PMID- 24914084
TI  - Pulmonary tuberculosis complicating asbestosis.

PMID- 24914083
TI  - Amelanotic melanoma masquerading as a pyogenic granuloma: caution warranted.

PMID- 24914087
TI  - No mean city: adolescent health and risk behaviours in a UK urban setting.
AB  - BACKGROUND: The adult population of Glasgow has worse health than in the rest of
      Scotland, only partially explained by deprivation. Little is known about the
      health of young Glaswegians. METHODS: The 2010 Health Behaviour in School-aged
      Children survey data were analysed using multilevel modelling to compare outcomes
      in Glasgow relative to the rest of Scotland. RESULTS: Glasgow adolescents had
      similar or better self-reported health on some measures--e.g. adjusting for age
      and sex, OR for 'very happy' was 0.93 (95% CI = (0.75, 1.14))--and the beta
      coefficient for positive GHQ-12 was 2.79 (0.72, 4.85) compared with the rest of
      Scotland. However, many health aspects were worse in Glasgow especially for
      eating and sedentary behaviour, subjective health and aggression, e.g. the OR for
      'daily consumption of vegetables' was 0.59 (0.46, 0.77), of reporting 'excellent
      health' was 0.66 (0.50, 0.87); headaches was 1.40 (1.09, 1.80); however drinking
      alcohol in the past week was lower (OR 0.71 (0.50, 0.99)) and smoking, similar.
      Adjustment for family affluence and school type marginally attenuated the
      association with Glasgow. CONCLUSIONS: The worse health experienced by Glasgow
      adults is only partially seen among young people in Glasgow; however, these are
      seen at the youngest ages in the study.

PMID- 24914085
TI  - Medium is the message: moderate parental control of feeding correlates with
      improved weight outcome in a pediatric obesity intervention.
AB  - OBJECTIVE: Previous studies have suggested complex associations among variables
      related to parental control of feeding and child/adolescent obesity. The current
      study examined associations between parental food control variables and weight
      outcomes in the context of a behaviorally based family treatment program.
      METHODS: Parents of youths (n = 93) enrolled in a clinical trial comparing 2
      weight management interventions completed the Child Feeding Questionnaire pre-
      and post-treatment, and at a 12-month follow-up. RESULTS: Latent growth curve
      modeling indicated that mean levels of restriction decreased over the course of
      treatment in the Positively Fit (PF) condition. Youths in the PF treatment
      condition whose parents increased their restriction of food experienced greater
      decreases in zBMI over treatment. CONCLUSIONS: Results echo previous reports that
      high and low parental control over food intake are associated with higher zBMI.
      Moderate parental control can be associated with beneficial outcomes in youths
      enrolled in behavioral treatment programs for obesity.

PMID- 24914088
TI  - Optimal and early detection of acute kidney injury requires effective clinical
      decision support systems.

PMID- 24914089
TI  - Intensified pharmaceutical care is improving immunosuppressive medication
      adherence in kidney transplant recipients during the first post-transplant year:
      a quasi-experimental study.
AB  - BACKGROUND: Medication adherence is critical for transplant patients because the
      consequences of non-adherence can result in allograft loss and may be life
      threatening. METHODS: A prospective study with 74 renal transplant recipients
      using a sequential control group design was performed to investigate the impact
      of a pharmaceutical intensified care programme led by a clinical pharmacist on
      daily drug adherence during the first year after renal transplantation. Thirty
      nine patients of the control group received the already established standardized
      drug and transplant training, while 35 patients of the intensified care group
      (ICG) received additional inpatient and outpatient pharmaceutical care and
      counselling by a dedicated clinical pharmacist. Applied interventions were
      clustered and classified using the behaviour change technique taxonomy according
      to Michie. Adherence to immunosuppressive drug therapy was monitored up to 1 year
      using a medication event monitoring system, pill count (PC), drug holiday (DH)
      occurrence, Morisky questionnaire and self-report. RESULTS: Sixty-seven patients
      (35 of the standard care and 32 of the ICG) were analysed. Implementation of DA
      was significantly (P = 0.014) improved in patients of the ICG (91%) compared with
      SCG (75%) during the first year after transplantion. Daily adherence measures
      were already improved within 30-40 days after start of intensified patient care
      and continued throughout the study period. Intensified care patients also showed
      significantly better results for taking adherence (P = 0.006), PC (P = 0.008) and
      DHs (P = 0.001). CONCLUSIONS: The additional, intensified pharmaceutical care
      improved patients' medication adherence remarkably, suggesting that the applied
      additional care programme has the potential to improve outcomes after organ
      transplantation.

PMID- 24914086
TI  - The influence of condition parameters and internalizing symptoms on social
      outcomes in youth with spina bifida.
AB  - OBJECTIVE: To test a model of social competence in youth with spina bifida (SB).
      Involvement in social activities was expected to mediate associations between SB
      related condition parameters (pain, body mass index, and motor function) and
      social competence. Internalizing symptoms were predicted to amplify the negative
      impact of condition parameters on social activity involvement. METHODS: 108 youth
      with SB, their caregivers, peers, and teachers participated in a multimethod
      study that included cognitive testing, questionnaires, and observational
      interaction tasks. RESULTS: Social activity involvement partially mediated the
      relation between pain and lower social competence. Internalizing symptoms had a
      significant indirect effect on social competence via decreased involvement in
      social activities. CONCLUSIONS: Pain and internalizing symptoms interfere with
      social activity involvement, which is, in turn, important for social competence
      development in youth with SB. Assessing and treating these condition parameters
      and activity factors may be important areas of focus in clinical practice and
      research with these youth.

PMID- 24914072
TI  - Gadolinium-based compounds induce NLRP3-dependent IL-1beta production and
      peritoneal inflammation.
AB  - OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing
      disorder that may develop in patients with chronic kidney disease after
      administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting
      of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis
      subsequently develops. However, the precise mechanism by which fibrosis occurs in
      NSF is incompletely understood. Because other profibrotic agents, such as silica
      or asbestos, activate the nucleotide-binding oligomerisation domain (NOD)-like
      receptor protein 3 (NLRP3) inflammasome and initiate interleukin (IL)-1beta
      release with the subsequent development of fibrosis, we evaluated the effects of
      GBCAs on inflammasome activation. METHODS: Bone marrow derived macrophages from
      C57BL/6, Nlrp3(-/-) and Asc(-/-) mice were incubated with three Gd-containing
      compounds and IL-1beta activation and secretion was detected by ELISA and western
      blot analysis. Inflammasome activation and regulation was investigated in IL-4-
      and interferon (IFN)gamma-polarised macrophages by ELISA, quantitative real time
      (qRT)-PCR and NanoString nCounter analysis. Furthermore, C57BL/6 and Nlrp3(-/
      )mice were intraperitoneally injected with GBCA and recruitment of inflammatory
      cells to the peritoneum was analysed by fluorescence-activated cell sorting
      (FACS). RESULTS: Free Gd and GBCAs activate the NLRP3 inflammasome and induce IL
      1beta secretion in vitro. Gd-diethylenetriaminepentaacetic acid also induces the
      recruitment of neutrophils and inflammatory monocytes to the peritoneum in vivo.
      Gd activated IL-4-polarised macrophages more effectively than IFNgamma-polarised
      macrophages, which preferentially expressed genes known to downregulate
      inflammasome activity. CONCLUSIONS: These data suggest that Gd released from
      GBCAs triggers a NLRP3 inflammasome-dependent inflammatory response that leads to
      fibrosis in an appropriate clinical setting. The preferential activation of IL-4
      differentiated macrophages is consistent with the predominantly fibrotic
      presentation of NSF.

PMID- 24914090
TI  - The effect of FoxO1 on the proliferation of rat mesangial cells under high
      glucose conditions.
AB  - BACKGROUND: Hyperproliferation of glomerular mesangial cells (MCs) is a major
      pathological characteristic in the early stage of diabetic nephropathy (DN). We
      have previously confirmed that forkhead transcription factor O1 (FoxO1) was
      significantly downregulated in both the renal cortex of DN rats and MCs cultured
      under high-glucose (HG) conditions, but the effects and mechanisms of FoxO1
      involved in the hyperproliferation of MCs are still unclear. This study aims to
      investigate whether FoxO1 regulates the hyperproliferation of MCs induced under
      high-glucose conditions, through modulating the cyclin-dependent kinase inhibitor
      (CKI), p27. METHODS: Lentiviral vectors of LV-constitutively active FoxO1 (CA
      FoxO1) and LV-small interfering RNA (siRNA)-FoxO1 were constructed to up- and
      downregulate FoxO1. Similarly, LV-NC-FoxO1 was used as negative control (NC). Rat
      MCs were cultured in normal glucose (5.6 mM) medium, HG (30 mM) medium, HG with
      LV-NC-FoxO1, HG with LV-CA-FoxO1 and HG with LV-siRNA-FoxO1 for 72 h. Cell
      proliferation, cell cycle progression, messenger RNA and protein expression of
      FoxO1, p27, cyclin D1 and CDK4 were detected by methyl thiazolyl tetrazolium
      assay, flow cytometry, quantitative real-time polymerase chain reaction and
      western blotting, respectively. RESULTS: MCs exposed to HG medium triggered
      hyperproliferation of MCs. Nevertheless, overexpression of FoxO1 caused by LV-CA
      FoxO1 promoted cell cycle arrest at the G0/G1 phase and attenuated proliferation,
      which was associated with upregulation of p27 and downregulation of cyclin D1 and
      CDK4. Moreover, specific degradation of FoxO1 by LV-siRNA-FoxO1 caused a decrease
      of p27, increase of cyclin D1 and CDK4, overrode the limited cell cycle and
      stimulated proliferation of MCs. CONCLUSIONS: Overexpression of FoxO1 caused
      upregulation of p27, which promoted cell cycle arrest and inhibited
      hyperproliferation of MCs induced by HG. Degradation of FoxO1 caused an increase
      in p27 and stimulated MC proliferation. These findings unveil part of the
      molecular mechanism of FoxO1 regulation of MC hyperproliferation induced by HG.

PMID- 24914092
TI  - 'That Obscure Object of Desire': in systemic lupus erythematosus B-cell
      activating factor/B-lymphocyte stimulator is targeted both by the immune system
      and by physicians.
AB  - Systemic lupus erythematosus (SLE) is characterized by autoantibodies that
      mediate tissue injury. However, the pathogenesis of SLE remains poorly understood
      and available therapeutic approaches are not fully satisfactory. Belimumab, a
      monoclonal antibody that neutralizes B-cell activating factor (BAFF), was the
      first drug approved to treat SLE in more than 50 years. However, it is not
      labelled for use in severe lupus nephritis. Recently, a novel high-throughput
      multiplex protein microarray platform to profile circulating immunoglobulin G
      (IgG) autoantibodies in SLE patients identified IgG autoantibodies against
      several cytokines and growth factors at higher titres in SLE patients than in
      controls. The presence of autoantibodies to BAFF was validated in a subset of SLE
      patients by enzyme-linked immunosorbent assay. Low levels of anti-BAFF
      autoantibodies were also present in healthy controls. The association of anti
      BAFF reactivity to clinical features and response to therapy was not addressed.
      However, preliminary data suggested an association to an interferon-alpha
      responsive mRNA signature, itself associated with severity. Functional studies
      disclosed a neutralizing activity of autoantibodies against BAFF. These findings
      raise new questions regarding the role of BAFF in SLE and the functional and
      therapeutic significance of anti-BAFF and anti-cytokine autoantibodies. 

PMID- 24914094
TI  - Anti-viral drugs in flu: not that good?

PMID- 24914093
TI  - Proteomic analysis of Class IV lupus nephritis.
AB  - BACKGROUND: There have been several attempts to standardize the definition and
      increase reproducibility in classifying lupus nephritis (LN). The last was made
      by the International Society of Nephrology and Renal Pathology Society in 2003
      where the introduction of Class IV subcategories (global and segmental) was
      introduced. METHODS: We investigated whether this subdivision is important using
      a proteomics approach. All patients with renal biopsies along with their clinical
      outcome of LN were identified and regrouped according to the above 2003
      classifications. Fresh-frozen renal biopsies of Class IV LN (global and
      segmental), antineutrophil cytoplasmic antibody-associated vasculitis and normal
      tissue were analyzed using two-dimensional gel electrophoresis (2-DE) and mass
      spectrometry. Differentially expressed proteins were identified and subjected to
      principal component analysis (PCA), and post hoc analysis for the four sample
      groups. RESULTS: PCA of 72 differentially expressed spots separated Class IV
      global and Class IV segmental from both normal and antineutrophil cytoplasmic
      antibody-associated vasculitis (ANCA). The 28 identified proteins were used in a
      post hoc analysis, and showed that IV-global and IV-segmental differ in several
      protein expression when compared with normal and ANCA. To confirm the proteomic
      results, a total of 78 patients (50 Class IV-Global and 28 Class IV-Segmental)
      were re-classified according to 2003 classification. There was no difference in
      therapy between the groups. The renal survival and patient survivals were similar
      in both groups. CONCLUSIONS: There is no strong evidence to support a different
      outcome between the two subcategories of Class-IV LN and, they should thus be
      treated the same until further studies indicate otherwise.

PMID- 24914091
TI  - Pregnancy after kidney transplantation: outcome and anti-human leucocyte antigen
      alloimmunization risk.
AB  - BACKGROUND: Kidney transplantation increases the chances for pregnancy and live
      birth for women with end-stage kidney disease. The aims of this study were to
      describe the outcomes of pregnancies in women with a kidney transplant and to
      evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization.
      METHODS: We analysed 61 pregnancies that occurred in 46 patients after having
      excluded 10 miscarriages during the first trimester and 10 other pregnancies from
      which important data were missing. Anti-HLA antibodies were screened using the
      Luminex assay. RESULTS: Overall, the live birth rate was 83% (94% after exclusion
      of miscarriages during the first trimester). Pre-eclampsia and gestational
      diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was
      an independent predictive factor for gestational diabetes. Twenty-four newborns
      (42%) were premature (<37 weeks). The median birth weight was 2720 (1040-3730) g.
      Nine newborns (15%) had low birth weights (<2.5 kg). At least one severe
      complication occurred in 56% of pregnancies. A high glomerular-filtration rate
      (GFR) before pregnancy was the sole independent protective factor that avoided a
      severe complication. Death-censored kidney-allograft survival was 80.4% at 6
      years. De novo donor-specific anti-HLA antibodies were detected after only 5.9%
      of pregnancies: for two women, the father had the same HLA antigens as those from
      the deceased organ donor. The determination of the HLA of the father before
      pregnancy can better inform the woman about the possible impact of pregnancy on
      her kidney-allograft function. CONCLUSIONS: Despite many complications, the
      outcomes for pregnancy and kidney allografts are good. The risk of anti-HLA
      alloimmunization was low.

PMID- 24914095
TI  - Guidance on clinical research involving infants, children and young people: an
      update for researchers and research ethics committees.

PMID- 24914096
TI  - Parents' and carers' perceptions of acute paediatric admissions.

PMID- 24914097
TI  - Prolonged school non-attendance in adolescence: a practical approach.
AB  - Prolonged school non-attendance in adolescence poses a significant public health
      concern. Adverse outcomes for adolescents who have missed out on the social and
      academic benefits of high school include mental health disorders and economic,
      social and relationship difficulties that may persist into adulthood. Healthcare
      professionals are often consulted in cases of prolonged school non-attendance.
      Diagnosis and management of specific physical and mental health problems must be
      the health professional's initial priority, with the subsequent development of a
      management plan to assist with school reintegration. Using a specific framework,
      an understanding of the factors contributing to a young person's school non
      attendance can be developed. Intervention leading to a successful return to
      school has the potential to lower the risk of associated long-term adverse health
      outcomes.

PMID- 24914100
TI  - RNA regulatory networks in animals and plants: a long noncoding RNA perspective.
AB  - A recent highlight of genomics research has been the discovery of many families
      of transcripts which have function but do not code for proteins. An important
      group is long noncoding RNAs (lncRNAs), which are typically longer than 200 nt,
      and whose members originate from thousands of loci across genomes. We review
      progress in understanding the biogenesis and regulatory mechanisms of lncRNAs. We
      describe diverse computational and high throughput technologies for identifying
      and studying lncRNAs. We discuss the current knowledge of functional elements
      embedded in lncRNAs as well as insights into the lncRNA-based regulatory network
      in animals. We also describe genome-wide studies of large amount of lncRNAs in
      plants, as well as knowledge of selected plant lncRNAs with a focus on
      biotic/abiotic stress-responsive lncRNAs.

PMID- 24914098
TI  - An extensively hydrolysed rice protein-based formula in the management of infants
      with cow's milk protein allergy: preliminary results after 1 month.
AB  - BACKGROUND: Guidelines recommend extensively hydrolysed cow's milk protein
      formulas (eHF) in the treatment of infants diagnosed with cow's milk protein
      allergy (CMPA). Extensively hydrolysed rice protein infant formulas (eRHFs) have
      recently become available, and could offer a valid alternative. METHODS: A
      prospective trial was performed to evaluate the clinical tolerance of a new eRHF
      in infants with a confirmed CMPA. Patients were followed for 1 month. Clinical
      tolerance of the eRHF was evaluated with a symptom-based score (SBS) and growth
      (weight and length) was monitored. RESULTS: Thirty-nine infants (mean age 3.4
      months, range 0.5-6 months) diagnosed with CMPA were enrolled. All infants
      tolerated the eRHF and experienced a normal growth. CONCLUSIONS: In accordance
      with current guidelines, this eRHF is tolerated by more than 90% of children with
      proven CMPA with a 95% CI, and is an adequate alternative to cow's milk-based
      eHF. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01998074.

PMID- 24914101
TI  - Incidence, characteristics and risk factors for household and neighbourhood
      injury among young children in semiurban Ghana: a population-based household
      survey.
AB  - BACKGROUND: There are few population-based studies on household child injury in
      African countries. OBJECTIVES: To determine the incidence, characteristics and
      risk factors of household and neighbourhood injury among children in semiurban
      communities in Kumasi, Ghana. METHODS: We conducted a cross-sectional population
      weighted survey of 200 randomly selected caregivers of children under 18,
      representing 6801 households. Caregivers were interviewed about moderate to
      severe childhood injuries occurring within the past 6 months, for which the child
      staying home from school or activity, and/or required medical care. Multivariable
      logistic regression was used to identify factors associated with injury risk.
      RESULTS: Annual injury incidence was 593.5 injuries per 1000 children. Common
      causes of injury were falls (315.7 injuries per 1000 children), followed by
      cuts/lacerations and burns. Most injuries (93.8%) were of moderate severity.
      Children whose caregivers were hourly workers (AOR=1.97; 95% CI 1.06 to 3.68) had
      increased odds of sustaining an injury compared to those of unemployed
      caregivers. Girls had decreased odds of injury (AOR=0.59; 95% CI 0.39 to 0.91).
      Cooking outdoors (AOR=0.45; 95% CI 0.27 to 0.76) and presence of
      cabinet/cupboards (AOR=0.41; 95% CI 0.24 to 0.70) in the house were protective.
      Among children under 5 years of age, living in uncompleted accommodation was
      associated with higher odds of injury compared with living in a rented single
      room (AOR=3.67; 95% CI 1.17 to 11.48). CONCLUSIONS: The incidence of household
      and neighbourhood child injury is high in semiurban Kumasi. We identified several
      novel injury risk factors (hourly work, younger children) and protective factors
      (cooking outdoors, presence of cabinet/cupboards). These data may identify
      priorities for household injury prevention.

PMID- 24914107
TI  - Quebec passes right-to-die law.

PMID- 24914102
TI  - Esophageal perforation during or after conformal radiotherapy for esophageal
      carcinoma.
AB  - The aim of this study was to analyze the risk factors and prognosis for patients
      with esophageal perforation occurring during or after radiotherapy for esophageal
      carcinoma. We retrospectively analyzed 322 patients with esophageal carcinoma.
      These patients received radiotherapy for unresectable esophageal tumors, residual
      tumors after operation, or local recurrence. Of these, 12 had radiotherapy to the
      esophagus before being admitted, 68 patients had concurrent chemoradiotherapy
      (CRT), and 18 patients had esophageal perforation after RT (5.8%). Covered self
      expandable metallic stents were placed in 11 patients. Two patients continued RT
      after stenting and control of infection; one of these suffered a new perforation,
      and the other had a massive hemorrhage. The median overall survival was 2 months
      (0-3 months) compared with 17 months in the non-perforation group. In univariate
      analysis, the Karnofsky performance status (KPS) being <= 70, age younger than
      60, T4 stage, a second course of radiotherapy to the esophagus, extracapsular
      lymph nodes (LN) involving the esophagus, a total dose >100 Gy (biologically
      effective dose-10), and CRT were risk factors for perforation. In multivariate
      analysis, age younger than 60, extracapsular LN involving the esophagus, T4
      stage, and a second course of radiotherapy to the esophagus were risk factors. In
      conclusion, patients with T4 stage, extracapsular LN involving the esophagus, and
      those receiving a second course of RT should be given particular care to avoid
      perforation. The prognosis after perforation was poor.

PMID- 24914110
TI  - Obtaining consent to a life-sustaining treatment for a patient with a major
      psychiatric illness.

PMID- 24914106
TI  - A rare case of ipsilateral shoulder and thumb CMC joint neuropathic arthropathy.
AB  - Neuropathic arthropathy (Charcot joints) most frequently affect the weight
      bearing joints of the body, are commonly associated with a variety of medical and
      neurological conditions and are notoriously difficult to treat due to the nature
      of the underlying pathology. We present a case of ipsilateral shoulder and thumb
      carpometacarpal (CMC) joint neuropathic arthropathy secondary to cervical
      syringomyelia. To our knowledge, this is the first reported case in the
      literature of this rare association. 

PMID- 24914108
TI  - 10 health stories that mattered: May 31-Jun.6.

PMID- 24914109
TI  - Harper skirts transparency on foreign aid.

PMID- 24914114
TI  - New UK council to curb psychiatry.

PMID- 24914104
TI  - Determining leaf trajectories for dynamic multileaf collimators with
      consideration of marker visibility: an algorithm study.
AB  - The purpose of this study was to develop a leaf-setting algorithm for Dynamic
      Multileaf Collimator-Intensity-Modulated Radiation Therapy (DMLC-IMRT) for
      optimal marker visibility. Here, a leaf-setting algorithm (called a Delta
      algorithm) was developed with the objective of maximizing marker visibility so as
      to improve the tracking effectiveness of fiducial markers during treatment
      delivery. The initial leaf trajectories were generated using a typical leaf
      setting algorithm, then the leaf trajectories were adjusted by Delta algorithm
      operations (analytical computations and a series of matrix calculations) to
      achieve the optimal solution. The performance of the Delta algorithm was
      evaluated with six test fields (with randomly generated intensity profiles) and
      15 clinical fields from IMRT plans of three prostate cancer patients. Compared
      with the initial solution, the Delta algorithm kept the total delivered
      intensities (TDIs) constant (without increasing the beam delivery time), but
      improved marker visibility (the percentage ratio of marker visibility time to
      beam delivery time). For the artificial fields (with three markers), marker
      visibility increased from 68.00-72.00% for a small field (5 * 5), from 38.46
      43.59% for a medium field (10 * 10), and from 28.57-37.14% for a large field (20
      * 20). For the 15 clinical fields, marker visibility increased 6-30% for eight
      fields and > 50% for two fields but did not change for five fields. A Delta
      algorithm was proposed to maximize marker visibility for DMLC-IMRT without
      increasing beam delivery time, and this will provide theoretical fundamentals for
      future studies of 4D DMLC tracking radiotherapy. 

PMID- 24914103
TI  - Delayed renal dysfunction after total body irradiation in pediatric malignancies.
AB  - The purpose of this study was to retrospectively evaluate the incidence of
      delayed renal dysfunction after total body irradiation (TBI) in long-term
      survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and
      2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for
      HSCT at Chiba University Hospital. Nine patients who survived for more than 5
      years were enrolled in this study. No patient had any evidence of renal
      dysfunction prior to the transplant according to their baseline creatinine
      levels. The median age at the time of diagnosis was 6 years old (range: 1-17
      years old). The follow-up period ranged from 79-170 months (median: 140 months).
      Renal dysfunction was assessed using the estimated glomerular filtration rate
      (eGFR). The TBI dose ranged from 8-12 Gy delivered in 3-6 fractions over 2-3 d.
      The patients were treated with linear accelerators in the supine position, and
      the radiation was delivered to isocentric right-left and left-right fields via
      the extended distance technique. The kidneys and the liver were not shielded
      except in one patient with a left adrenal neuroblastoma. No patient required
      hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The
      remaining patients did not demonstrate any eGFR deterioration. Only one patient
      developed hypertension. By evaluating the changes in eGFR, renal dysfunction
      among long-term survivors of TBI/HSCT could be detected. Our results suggested
      that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects
      renal function. 

PMID- 24914112
TI  - Questioning the assumptions about type 2 diabetes.

PMID- 24914111
TI  - Chikungunya.

PMID- 24914113
TI  - Epilepsy surgery in childhood: no longer the treatment of last resort.

PMID- 24914105
TI  - Investigation into the role of the cholinergic system in radiation-induced damage
      in the rat liver and ileum.
AB  - It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory
      and anti-inflammatory cytokines. The role of the cholinergic system in radiation
      induced inflammatory responses and tissue damage remains unclear. Therefore, the
      present study was designed to determine the radio-protective properties of the
      cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy
      single-fraction whole-abdominal irradiation and were then decapitated at either
      36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal
      physiological saline (1 ml/kg), physostigmine (80 ug/kg) or atropine (50 MUg/kg)
      twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues
      were obtained in which TNF-alpha, IL-1beta and IL-10 levels were assayed using
      ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed
      and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1beta and
      TNF-alpha increased significantly following radiation (P < 0.01 and P < 0.001,
      respectively) as compared with non-irradiated controls, and physostigmine
      treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and
      P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly
      changed following radiation, whereas physostigmine augmented IL-10 levels during
      the late phase (P < 0.01). In the liver and ileum homogenates, IL-1beta and TNF
      alpha levels were also elevated following radiation, and this effect was
      inhibited by physostigmine treatment but not by atropine. Similarly,
      physostigmine also reversed the changes in MPO activity and in the caspase-3
      levels in the liver and ileum. Histological examination revealed related changes.
      Physostigmine experiments suggested that ACh has a radio-protective effect not
      involving the muscarinic receptors. 

PMID- 24914116
TI  - Drug safety legislation closer to passing.

PMID- 24914118
TI  - Nicotine poisoning increase due to e-cigarettes.

PMID- 24914115
TI  - Risk of febrile seizures after first dose of measles-mumps-rubella-varicella
      vaccine: a population-based cohort study.
AB  - BACKGROUND: The combination measles-mumps-rubella-varicella (MMRV) vaccine
      currently used in Canada (Priorix-Tetra) may increase the risk of febrile
      seizures relative to the separate vaccines (MMR and varicella) previously
      administered. We determined the risk of febrile seizure after the first dose of
      MMRV, as well as any additional risk for children at high risk for seizures
      because of pre-existing medical conditions. METHODS: In this retrospective,
      population-based cohort study, we compared the risk of seizures after the first
      dose of MMRV with the risk after same-day administration of separate MMR and
      varicella vaccines (MMR+V) in children 12 to 23 months of age in the province of
      Alberta. We deterministically linked vaccination data to health service
      utilization data for seizures. We used Poisson regression, with adjustment for
      age and calendar year, to determine the risk for the full cohort and for high
      risk children. RESULTS: The risk of seizures 7 to 10 days after vaccination was
      twice as high with MMRV as with MMR+V (relative risk [RR] 1.99, 95% confidence
      interval [CI] 1.30-3.05). The excess absolute risk of seizures was 3.52 seizures
      per 10 000 doses of MMRV relative to MMR+V. In high-risk children, the risk was
      not differentially higher for MMRV (RR 1.30, 95% CI 0.60-2.79). INTERPRETATION:
      Despite an increased risk of febrile seizures following MMRV (compared with
      MMR+V), the absolute level of risk was small. Policy-makers need to balance these
      findings with the potential benefits of administering the combination vaccine or
      determine whether the choice of vaccine rests with clinicians and/or parents.

PMID- 24914119
TI  - Divide over treating opioid-addicted moms.

PMID- 24914117
TI  - Surgical management of epilepsy.

PMID- 24914120
TI  - Population pharmacokinetic-pharmacodynamic analysis of voriconazole and
      anidulafungin in adult patients with invasive aspergillosis.
AB  - To evaluate the exposure-response relationships for efficacy and safety of
      voriconazole and anidulafungin in adult patients with invasive aspergillosis
      (IA), a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed
      with data from a phase 3, prospective, double-blind, comparative study evaluating
      voriconazole and anidulafungin combination therapy versus voriconazole (and
      placebo) monotherapy. Anidulafungin/placebo treatment duration was 2 to 4 weeks,
      and voriconazole treatment duration was 6 weeks. Efficacy (6-week all-causality
      mortality and 6-week global response [n = 176]) and safety (hepatic [n = 238],
      visual [n = 199], and psychiatric [n = 183] adverse events [AEs]) endpoints were
      analyzed separately using a binary logistic regression model. In IA patients
      receiving voriconazole monotherapy, no positive associations between voriconazole
      exposure and efficacy or safety were identified. In IA patients receiving
      combination therapy, no positive associations between voriconazole or
      anidulafungin exposures and efficacy were identified. The 6-week survival rate
      tended to increase as anidulafungin treatment duration increased; this finding
      should be considered with caution. Additionally, in IA patients receiving
      combination therapy, a positive association between voriconazole and
      anidulafungin exposures (area under the curve [AUC] and trough concentration
      [C(min)]) and hepatic AEs was established; a weak positive association between
      voriconazole exposure (AUC and C(min)) and psychiatric AEs was also established,
      but no association between voriconazole exposure and visual AEs was identified.
      Besides the drug exposures, no other covariates (i.e., CYP2C19 genotype status,
      age, weight, body mass index, sex, race, or neutropenia status) were identified
      as significant predictors of the efficacy and safety endpoints in IA patients.
      This study was registered on ClinicalTrials.gov (NCT00531479).

PMID- 24914126
TI  - Surveying the knowledge landscape in sub-Saharan Africa: methodology.
AB  - OBJECTIVE: To describe in detail the methods followed in each of the qualitative
      and quantitative surveys of national health information, research and knowledge
      systems and research institutions. DESIGN: Cross-sectional surveys. SETTING:
      National health information and research systems, and 847 health research
      institutions in 42 countries in the World Health Organization (WHO) African
      Region. PARTICIPANTS: Key informants from health research institutions,
      ministries of health and statistical offices. MAIN OUTCOME MEASURES: Stewardship,
      financing, ethics, human and material resources and output of health information
      and research systems. RESULTS: Key informants were used to collect data to assess
      national research systems in 44 countries in the Region. The same method was
      followed in assessing national information systems in 17 countries and knowledge
      systems for health in 44 countries. These assessments included a detailed review
      of the state of data sources in the Region and their effect on measuring progress
      on the health-related Millennium Development Goals. A concurrent survey employed
      a structured questionnaire (the WHO Health Research Systems Analysis
      Questionnaire) to assess the capacity of 847 health research institutions in 42
      countries. Stewardship, financing, ethics, human and material resources and
      research output were assessed. CONCLUSIONS: The logistics and resources involved
      in surveying the knowledge landscape in the 42 countries were substantial.
      However, the investment was worthwhile as the results of the surveys can be used
      to inform policy-making and decision-making, as well as to establish a regional
      database of national health information, research and knowledge systems.

PMID- 24914127
TI  - Health information systems in Africa: descriptive analysis of data sources,
      information products and health statistics.
AB  - OBJECTIVE: To identify key data sources of health information and describe their
      availability in countries of the World Health Organization (WHO) African Region.
      METHODS: An analytical review on the availability and quality of health
      information data sources in countries; from experience, observations, literature
      and contributions from countries. SETTING: Forty-six Member States of the WHO
      African Region. PARTICIPANTS: No participants. MAIN OUTCOME MEASURES: The state
      of data sources, including censuses, surveys, vital registration and health care
      facility-based sources. RESULTS: In almost all countries of the Region, there is
      a heavy reliance on household surveys for most indicators, with more than 121
      household surveys having been conducted in the Region since 2000. Few countries
      have civil registration systems that permit adequate and regular tracking of
      mortality and causes of death. Demographic surveillance sites function in several
      countries, but the data generated are not integrated into the national health
      information system because of concerns about representativeness. Health
      management information systems generate considerable data, but the information is
      rarely used because of concerns about bias, quality and timeliness. To date, 43
      countries in the Region have initiated Integrated Disease Surveillance and
      Response. CONCLUSIONS: A multitude of data sources are used to track progress
      towards health-related goals in the Region, with heavy reliance on household
      surveys for most indicators. Countries need to develop comprehensive national
      plans for health information that address the full range of data needs and data
      sources and that include provision for building national capacities for data
      generation, analysis, dissemination and use.

PMID- 24914123
TI  - Switch-loop flexibility affects transport of large drugs by the promiscuous AcrB
      multidrug efflux transporter.
AB  - Multidrug efflux transporters recognize a variety of structurally unrelated
      compounds for which the molecular basis is poorly understood. For the resistance
      nodulation and cell division (RND) inner membrane component AcrB of the AcrAB
      TolC multidrug efflux system from Escherichia coli, drug binding occurs at the
      access and deep binding pockets. These two binding areas are separated by an 11
      amino-acid-residue-containing switch loop whose conformational flexibility is
      speculated to be essential for drug binding and transport. A G616N substitution
      in the switch loop has a distinct and local effect on the orientation of the loop
      and on the ability to transport larger drugs. Here, we report a distinct
      phenotypical pattern of drug recognition and transport for the G616N variant,
      indicating that drug substrates with minimal projection areas of >70 A(2) are
      less well transported than other substrates. 

PMID- 24914122
TI  - Resistance to colistin associated with a single amino acid change in protein PmrB
      among Klebsiella pneumoniae isolates of worldwide origin.
AB  - A series of colistin-resistant Klebsiella pneumoniae isolates recovered from
      different countries was investigated in order to evaluate the involvement of the
      PmrA/PmrB two-component system in this resistance. Six isolates possessed a
      mutated PmrB protein, which is encoded by the pmrB gene, part of the pmrCAB
      operon involved in lipopolysaccharide modification. The same amino acid
      substitution (Thr157Pro) in PmrB was identified in the six isolates. The six
      isolates belonged to four distinct clonal groups, recovered in South Africa
      (sequence type 14 [ST14]), Turkey (ST101), and Colombia (ST258 and ST15). Three
      out of the four clones produced a carbapenemase, OXA-181, OXA-48, or KPC-3, while
      a single isolate did not produce any carbapenemase. Expression assays revealed an
      overexpression of the pmrA (70-fold), pmrB (70-fold), pmrC (170-fold), and pmrK
      (40-fold) genes in the pmrB-mutated isolate compared to expression of the pmrB
      wild-type isogenic K. pneumoniae isolate, confirming that the PmrB substitution
      was responsible for increased expression levels of those genes. Complementation
      assays leading to the expression of a wild-type PmrB protein restored the
      susceptibility to colistin in all isolates, confirming that the substitution in
      PmrB was responsible for the resistance phenotype. This study identified a key
      amino acid located in the PmrB protein as being responsible for the
      overexpression of pmrCAB and pmrHFIJKLM operons, leading to resistance to
      colistin. 

PMID- 24914124
TI  - Evaluation of a fluorescence-based method for antibabesial drug screening.
AB  - In vitro evaluation of chemotherapeutic agents against Babesia and Theileria
      parasites has become routine, and the effectiveness of these chemicals is usually
      determined by comparing the parasitemia dynamics of untreated and treated
      parasites. Although microscopy is widely used to calculate parasitemia, several
      disadvantages are associated with this technique. The present study evaluated a
      fluorescence-based method using SYBR green I stain (SG I) to screen antibabesial
      agents in in vitro cultures of Babesia bovis. The linearity between relative
      fluorescence units (RFU) and parasitemia was found to be well correlated with a
      0.9944 goodness-of-fit (r(2)) value. Subsequently, 50% inhibitory concentration
      (IC50) values were calculated for 3 antiprotozoan agents, diminazene aceturate,
      nimbolide, and gedunin, by this method. For diminazene aceturate and nimbolide,
      the IC(50)s determined by the fluorescence-based method (408 nM and 8.13 MUM,
      respectively) and microscopy (400.3 nM and 9.4 MUM, respectively) were in
      agreement. Furthermore, the IC50 of gedunin determined by the fluorescence-based
      method (19 MUM) was similar to the recently described microscopy-based value
      (21.7 MUM) for B. bovis. Additionally, the Z' factor (0.80 to 0.90), signal-to
      noise (S/N) ratio (44.15 to 87.64), coefficient of variation at the maximum
      signal (%CVmax) (0.50 to 2.85), and coefficient of variation at the minimum
      signal (%CVmin) (1.23 to 2.21) calculated for the fluorescence method using
      diminazene aceturate were comparable to those previously determined in malaria
      research for this assay. These findings suggest that the fluorescence-based
      method might be useful for antibabesial drug screening and may have potential to
      be developed into a high-throughput screening (HTS) assay.

PMID- 24914129
TI  - Research and its governance in health research institutions in sub-Saharan
      African countries: results of a questionnaire-based survey.
AB  - SUMMARY: Objective: To describe governance and stewardship of research in health
      research institutions in the World Health Organization (WHO) African Region.
      Design: A structured questionnaire was used to solicit information on governance
      and stewardship from health research institutions. Setting: Forty-two Member
      States of the WHO African Region. Participants: Key informants from the
      respondent health research institutions in the respondent sub-Saharan African
      countries. Main outcome measures: Institutions' participation in setting the
      national health research agenda. Institutional research priorities, scientific
      reviews and governance structure. Results: During the previous 12 months, the
      heads of 49% of respondent health research institutions participated in the
      setting or coordination of national research priorities. The most frequently
      cited priorities for contributing to or performing research were improving health
      programmes, producing new knowledge, influencing health policies and conducting
      operational research. For 78% of respondent institutions, scientific review was
      required for research funded directly by the institution, and for 73% of
      respondent institutions, scientific review was required for research not funded
      by the institution. However, most respondent institutions did not have written
      policies or guidelines, either for the scientific review of proposals (70%) or
      regarding conflict of interest on scientific review committees (80%).
      Conclusions: Some health research institutions demonstrate good practice in terms
      of the establishment of structures and processes for governance and stewardship,
      many others do not. There is a need for the strengthening of the stewardship
      capacity of research institutions in the Region.

PMID- 24914121
TI  - Comparative genomics of an IncA/C multidrug resistance plasmid from Escherichia
      coli and Klebsiella isolates from intensive care unit patients and the utility of
      whole-genome sequencing in health care settings.
AB  - The IncA/C plasmids have been implicated for their role in the dissemination of
      beta-lactamases, including gene variants that confer resistance to expanded
      spectrum cephalosporins, which are often the treatment of last resort against
      multidrug-resistant, hospital-associated pathogens. A bla(FOX-5) gene was
      detected in 14 Escherichia coli and 16 Klebsiella isolates that were cultured
      from perianal swabs of patients admitted to an intensive care unit (ICU) of the
      University of Maryland Medical Center (UMMC) in Baltimore, MD, over a span of 3
      years. Four of the FOX-encoding isolates were obtained from subsequent samples of
      patients that were initially negative for an AmpC beta-lactamase upon admission
      to the ICU, suggesting that the AmpC beta-lactamase-encoding plasmid was acquired
      while the patient was in the ICU. The genomes of five E. coli isolates and six
      Klebsiella isolates containing bla(FOX-5) were selected for sequencing based on
      their plasmid profiles. An ~ 167-kb IncA/C plasmid encoding the FOX-5 beta
      lactamase, a CARB-2 beta-lactamase, additional antimicrobial resistance genes,
      and heavy metal resistance genes was identified. Another FOX-5-encoding IncA/C
      plasmid that was nearly identical except for a variable region associated with
      the resistance genes was also identified. To our knowledge, these plasmids
      represent the first FOX-5-encoding plasmids sequenced. We used comparative
      genomics to describe the genetic diversity of a plasmid encoding a FOX-5 beta
      lactamase relative to the whole-genome diversity of 11 E. coli and Klebsiella
      isolates that carry this plasmid. Our findings demonstrate the utility of whole
      genome sequencing for tracking of plasmid and antibiotic resistance gene
      distribution in health care settings.

PMID- 24914128
TI  - Overview of national health research systems in sub-Saharan Africa: results of a
      questionnaire-based survey.
AB  - OBJECTIVE: To assess the state of national health research systems of countries
      in the World Health Organization (WHO) African Region. DESIGN: A questionnaire
      based survey METHODS: Structured questionnaires were used to solicit health
      research systems' relevant information from key informants in each country.
      SETTING: Forty-six Member States of the WHO African Region. PARTICIPANTS: Key
      informants from the ministry of health in each country, with the support of WHO
      Country Offices. MAIN OUTCOME MEASURES: Presence of national health research
      policy or strategy, priority setting and ethical review of research. RESULTS: Of
      the 44 responding countries, 39 (89%) reportedly had an official national health
      policy and 37 (84%) had a strategic health plan. A total of 16 (36%) countries
      reportedly had a functional national health research governance mechanism, nine
      of which had clear terms of reference; nine (20%) countries had a functional
      national health research management forum. Functional ethical review committees
      were reported in 33 countries (75%). CONCLUSIONS: National health research
      systems were weak in the countries assessed. Significantly more resources should
      be allocated to strengthening these systems.

PMID- 24914130
TI  - Expenditures on health research in sub-Saharan African countries: results of a
      questionnaire-based survey.
AB  - OBJECTIVE: To estimate the sources of funds for health research (revenue) and the
      uses of these funds (expenditure). DESIGN: A structured questionnaire was used to
      solicit financial information from health research institutions. SETTING: Forty
      two sub-Saharan African countries. PARTICIPANTS: Key informants in 847 health
      research institutions in the 42 sub-Saharan African countries. MAIN OUTCOME
      MEASURES: Expenditure on health research by institutions, funders and subject
      areas. RESULTS: An estimated total of US$ 302 million was spent on health
      research by institutions that responded to the survey in the World Health
      Organization (WHO) African Region for the biennium 2005-2006. The most notable
      funders for health research activities were external funding, ministries of
      health, other government ministries, own funds and non-profit institutions. Most
      types of health research performers spent significant portions of their resources
      on in-house research, with medical schools spending 82% and government agencies
      62%. Hospitals spent 38% of their resources on management, and other institutions
      (universities, firms, etc.) spent 87% of their resources on capital investment.
      Research on human immunodeficiency virus/tuberculosis and malaria accounted for
      30% of funds, followed by research on other communicable diseases and maternal,
      perinatal and nutritional conditions (23%). CONCLUSIONS: Research on major health
      problems of the Region, such as communicable diseases, accounts for most of the
      research expenditures. However, the total expenditure is very low compared with
      other WHO regions.

PMID- 24914125
TI  - Highly sulfated K5 Escherichia coli polysaccharide derivatives inhibit
      respiratory syncytial virus infectivity in cell lines and human tracheal
      bronchial histocultures.
AB  - Respiratory syncytial virus (RSV) exploits cell surface heparan sulfate
      proteoglycans (HSPGs) as attachment receptors. The interaction between RSV and
      HSPGs thus presents an attractive target for the development of novel inhibitors
      of RSV infection. In this study, selective chemical modification of the
      Escherichia coli K5 capsular polysaccharide was used to generate a collection of
      sulfated K5 derivatives with a backbone structure that mimics the heparin/heparan
      sulfate biosynthetic precursor. The screening of a series of N-sulfated (K5-NS),
      O-sulfated (K5-OS), and N,O-sulfated (K5-N,OS) derivatives with different degrees
      of sulfation revealed the highly sulfated K5 derivatives K5-N,OS(H) and K5-OS(H)
      to be inhibitors of RSV. Their 50% inhibitory concentrations were between 1.07 nM
      and 3.81 nM in two different cell lines, and no evidence of cytotoxicity was
      observed. Inhibition of RSV infection was maintained in binding and attachment
      assays but not in preattachment assays. Moreover, antiviral activity was also
      evident when the K5 derivatives were added postinfection, both in cell-to-cell
      spread and viral yield reduction assays. Finally, both K5-N,OS(H) and K5-OS(H)
      prevented RSV infection in human-derived tracheal/bronchial epithelial cells
      cultured to form a pseudostratified, highly differentiated model of the
      epithelial tissue of the human respiratory tract. Together, these features put K5
      N,OS(H) and K5-OS(H) forward as attractive candidates for further development as
      RSV inhibitors. 

PMID- 24914131
TI  - Human resources in health research institutions in sub-Saharan African countries:
      results of a questionnaire-based survey.
AB  - OBJECTIVE: To describe human capacity and staff movement in national health
      research institutions in 42 sub-Saharan African countries. DESIGN: A structured
      questionnaire was used to solicit information on governance and stewardship from
      health research institutions. SETTING: Eight hundred and forty-seven health
      research institutions in 42 sub-Saharan African countries. PARTICIPANTS: Key
      informants from 847 health research institutions. MAIN OUTCOME MEASURES: The
      availability, mix and quality of human resources in health research institutions.
      RESULTS: On average, there were 122 females employed per respondent health
      research institution, compared with 159 males. For researchers, the equivalent
      figures were nine females to 17 males. The average annual gross salary of
      researchers varied between US$ 12,260 for staff with 5-10 years of experience and
      US$ 14,772 for the institution head. Of those researchers who had joined the
      institution in the previous 12 months, 55% were employed on a full-time basis. Of
      the researchers who left the institutions in the same period, 71% had a full-time
      contract. Among all those who left, those who left to a non-research sector and
      to another country accounted for two-thirds. CONCLUSIONS: The study revealed
      significant gaps in the area of human capacity development for research in
      Africa. The results showed a serious shortage of qualified staff engaged in
      health research, with a dearth of staff that held at least a master's degree or
      doctoral degree. Major efforts will be required to strengthen human resource
      capacity, including addressing the lack of motivation or time for research on the
      part of existing capable staff.

PMID- 24914132
TI  - Rapamycin relieves lentiviral vector transduction resistance in human and mouse
      hematopoietic stem cells.
AB  - Transplantation of genetically modified hematopoietic stem cells (HSCs) is a
      promising therapeutic strategy for genetic diseases, HIV, and cancer. However, a
      barrier for clinical HSC gene therapy is the limited efficiency of gene delivery
      via lentiviral vectors (LVs) into HSCs. We show here that rapamycin, an
      allosteric inhibitor of the mammalian target of rapamycin complexes, facilitates
      highly efficient lentiviral transduction of mouse and human HSCs and dramatically
      enhances marking frequency in long-term engrafting cells in mice.
      Mechanistically, rapamycin enhanced postbinding endocytic events, leading to
      increased levels of LV cytoplasmic entry, reverse transcription, and genomic
      integration. Despite increasing LV copy number, rapamycin did not significantly
      alter LV integration site profile or chromosomal distribution in mouse HSCs.
      Rapamycin also enhanced in situ transduction of mouse HSCs via direct
      intraosseous infusion. Collectively, rapamycin strongly augments LV transduction
      of HSCs in vitro and in vivo and may prove useful for therapeutic gene delivery.

PMID- 24914133
TI  - Hydroxyurea-inducible SAR1 gene acts through the Gialpha/JNK/Jun pathway to
      regulate gamma-globin expression.
AB  - Hydroxyurea (HU) is effectively used in the management of beta-hemoglobinopathies
      by augmenting the production of fetal hemoglobin (HbF). However, the molecular
      mechanisms underlying HU-mediated HbF regulation remain unclear. We previously
      reported that overexpression of the HU-induced SAR1 gene closely mimics the known
      effects of HU on K562 and CD34(+) cells, including gamma-globin induction and
      cell-cycle regulation. Here, we show that HU stimulated nuclear factor-kappaB
      interaction with its cognate-binding site on the SAR1 promoter to regulate
      transcriptional expression of SAR1 in K562 and CD34(+) cells. Silencing SAR1
      expression not only significantly lowered both basal and HU-elicited HbF
      production in K562 and CD34(+) cells, but also significantly reduced HU-mediated
      S-phase cell-cycle arrest and apoptosis in K562 cells. Inhibition of c-Jun N
      terminal kinase (JNK)/Jun phosphorylation and silencing of Gialpha expression in
      SAR1-transfected K562 and CD34(+) cells reduced both gamma-globin expression and
      HbF level, indicating that activation of Gialpha/JNK/Jun proteins is required for
      SAR1-mediated HbF induction. Furthermore, reciprocal coimmunoprecipitation assays
      revealed an association between forcibly expressed SAR1 and Gialpha2 or Gialpha3
      proteins in both K562 and nonerythroid cells. These results indicate that HU
      induces SAR1, which in turn activates gamma-globin expression, predominantly
      through the Gialpha/JNK/Jun pathway. Our findings identify SAR1 as an alternative
      therapeutic target for beta-globin disorders. 

PMID- 24914134
TI  - MicroRNA-155 influences B-cell receptor signaling and associates with aggressive
      disease in chronic lymphocytic leukemia.
AB  - High-level leukemia cell expression of micro-RNA 155 (miR-155) is associated with
      more aggressive disease in patients with chronic lymphocytic leukemia (CLL),
      including those cases with a low-level expression of zeta-chain-associated
      protein of 70 kD. CLL with high-level miR-155 expressed lower levels of Src
      homology-2 domain-containing inositol 5-phosphatase 1 and were more responsive to
      B-cell receptor (BCR) ligation than CLL with low-level miR-155. Transfection with
      miR-155 enhanced responsiveness to BCR ligation, whereas transfection with a miR
      155 inhibitor had the opposite effect. CLL in lymphoid tissue expressed higher
      levels of miR155HG than CLL in the blood of the same patient. Also, isolated
      CD5(bright)CXCR4(dim) cells, representing CLL that had been newly released from
      the microenvironment, expressed higher levels of miR-155 and were more responsive
      to BCR ligation than isolated CD5(dim)CXCR4(bright) cells of the same patient.
      Treatment of CLL or normal B cells with CD40-ligand or B-cell-activating factor
      upregulated miR-155 and enhanced sensitivity to BCR ligation, effects that could
      be blocked by inhibitors to miR-155. This study demonstrates that the sensitivity
      to BCR ligation can be enhanced by high-level expression of miR-155, which in
      turn can be induced by crosstalk within the tissue microenvironment, potentially
      contributing to its association with adverse clinical outcome in patients with
      CLL. 

PMID- 24914135
TI  - Identification of cereblon-binding proteins and relationship with response and
      survival after IMiDs in multiple myeloma.
AB  - Cereblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma
      (MM). Using 2 different methodologies, we identified 244 CRBN binding proteins
      and established relevance to MM biology by changes in their abundance after
      exposure to lenalidomide. Proteins most reproducibly binding CRBN (>fourfold vs
      controls) included DDB1, CUL4A, IKZF1, KPNA2, LTF, PFKL, PRKAR2A, RANGAP1, and
      SHMT2. After lenalidomide treatment, the abundance of 46 CRBN binding proteins
      decreased. We focused attention on 2 of these-IKZF1 and IKZF3. IZKF expression is
      similar across all MM stages or subtypes; however, IKZF1 is substantially lower
      in 3 of 5 IMiD-resistant MM cell lines. The cell line (FR4) with the lowest IKZF1
      levels also harbors a damaging mutation and a translocation that upregulates
      IRF4, an IKZF target. Clinical relevance of CRBN-binding proteins was
      demonstrated in 44 refractory MM patients treated with pomalidomide and
      dexamethasone therapy in whom low IKZF1 gene expression predicted lack of
      response (0/11 responses in the lowest expression quartile). CRBN, IKZF1, and
      KPNA2 levels also correlate with significant differences in overall survival. Our
      study identifies CRBN-binding proteins and demonstrates that in addition to CRBN,
      IKZF1, and KPNA2, expression can predict survival outcomes. 

PMID- 24914138
TI  - Hematopoietic stem cell transplantation donor sources in the 21st century:
      choosing the ideal donor when a perfect match does not exist.
AB  - Most patients who require allogeneic stem cell transplantation do not have a
      matched sibling donor, and many patients do not have a matched unrelated donor.
      In an effort to increase the applicability of transplantation, alternative donors
      such as mismatched adult unrelated donors, haploidentical related donors, and
      umbilical cord blood stem cell products are frequently used when a well matched
      donor is unavailable. We do not yet have the benefit of randomized trials
      comparing alternative donor stem cell sources to inform the choice of donor;
      however, the existing data allow some inferences to be made on the basis of
      existing observational and phase 2 studies. All 3 alternative donor sources can
      provide effective lymphohematopoietic reconstitution, but time to engraftment,
      graft failure rate, graft-versus-host disease, transplant-related mortality, and
      relapse risk vary by donor source. These factors all contribute to survival
      outcomes and an understanding of them should help guide clinicians when choosing
      among alternative donor sources when a matched related or matched unrelated donor
      is not available. 

PMID- 24914137
TI  - The biology of graft-versus-host disease: experimental systems instructing
      clinical practice.
AB  - The last 6 decades have seen major advances in the understanding of immunologic
      diseases, driven by preclinical animal models. Indeed, bone marrow
      transplantation (BMT) has its genesis in rodent models dating back to the 1950s.
      Allogeneic BMT and its major complication, graft-versus-host disease (GVHD),
      represent a paradigm for the translation of preclinical concepts into clinical
      practice. The appreciation that GVHD can be thought of as a stepwise escalation
      in immune activation characterized by eventual massive target tissue apoptosis
      has allowed the design of rational approaches to better manage patients. Here, we
      describe the pathophysiology of GVHD as defined in preclinical models, focusing
      on the successes and failures of this research to instruct and translate clinical
      practice. We also provide a commentary on the limitations of these models so that
      they may be better appreciated and addressed in future studies. Notable
      preclinical successes include the definition of modern immune suppression,
      reductions in conditioning intensity, posttransplant cyclophosphamide, and the
      promotion of regulatory T-cell reconstitution. New strategies including naive T
      cell depletion, focused cytokine and chemokine inhibition, and the blockade of
      costimulation now also appear highly promising and very likely to translate into
      patients in the near future. 

PMID- 24914136
TI  - Magnetic resonance imaging/angiography and transcranial Doppler velocities in
      sickle cell anemia: results from the SWiTCH trial.
AB  - The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared
      standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy)
      treatment to prevent recurrent stroke and manage iron overload in children
      chronically transfused over 7 years before enrollment. Standardized brain
      magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial
      Doppler (TCD) exams were performed at entry and exit, with a central blinded
      review. A novel MRA vasculopathy grading scale demonstrated frequent severe
      baseline left/right vessel stenosis (53%/41% >=Grade 4); 31% had no vessel
      stenosis on either side. Baseline parenchymal injury was prevalent (85%/79%
      subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children
      had low or uninterpretable baseline middle cerebral artery TCD velocities, which
      were associated with worse stenoses (incidence risk ratio [IRR] = 5.1, P <= .0001
      and IRR = 4.1, P < .0001) than normal velocities; only 2% to 12% had any
      conditional/abnormal velocity. Patients with adjudicated stroke (7) and transient
      ischemic attacks (19 in 11 standard/8 alternative arm subjects) had substantial
      parenchymal injury/vessel stenosis. At exit, 1 child (alternative arm) had a new
      silent infarct, and another had worse stenosis. SWiTCH neuroimaging data document
      severe parenchymal and vascular abnormalities in children with SCA and stroke and
      support concerns about chronic transfusions lacking effectiveness for preventing
      progressive cerebrovascular injury. The novel SWiTCH vasculopathy grading scale
      warrants validation testing and consideration for use in future clinical trials.
      This trial was registered at www.clinicaltrials.gov as #NCT00122980. 

PMID- 24914139
TI  - Current issues in chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) is a frequent and potentially life
      threatening complication of allogeneic hematopoietic stem cell transplantation.
      Increased transplantation of older patients and the more frequent use of
      unrelated donors has led to increased numbers of patients with this painful
      complication. Recent advances have been made in understanding the pathophysiology
      of chronic GVHD and in establishing precise criteria for diagnosis and
      classification of disease manifestations. These advances will hopefully pave the
      way for improving both the prophylaxis and treatment of chronic GVHD. 

PMID- 24914141
TI  - Introduction to the review series on "Advances in hematopoietic cell
      transplantation".

PMID- 24914140
TI  - Acute graft-versus-host disease: a bench-to-bedside update.
AB  - Over the past 5 years, many novel approaches to early diagnosis, prevention, and
      treatment of acute graft-versus-host disease (aGVHD) have been translated from
      the bench to the bedside. In this review, we highlight recent discoveries in the
      context of current aGVHD care. The most significant innovations that have already
      reached the clinic are prophylaxis strategies based upon a refinement of our
      understanding of key sensors, effectors, suppressors of the immune alloreactive
      response, and the resultant tissue damage from the aGVHD inflammatory cascade. In
      the near future, aGVHD prevention and treatment will likely involve multiple
      modalities, including small molecules regulating immunologic checkpoints,
      enhancement of suppressor cytokines and cellular subsets, modulation of the
      microbiota, graft manipulation, and other donor-based prophylaxis strategies.
      Despite long-term efforts, major challenges in treatment of established aGVHD
      still remain. Resolution of inflammation and facilitation of rapid immune
      reconstitution in those with only a limited response to corticosteroids is a
      research arena that remains rife with opportunity and urgent clinical need. 

PMID- 24914143
TI  - HIV-1 testing of young febrile adults seeking care for fever in sub-Sahara
      Africa.

PMID- 24914144
TI  - The birth of a new field.

PMID- 24914142
TI  - Conditioning regimens for hematopoietic cell transplantation: one size does not
      fit all.
AB  - An essential component of allogeneic and autologous hematopoietic cell
      transplantation (HCT) is the conditioning regimen administered before the
      hematopoietic cell infusion. Early regimens relied on dose intensity, assuming
      that high-dose chemoradiotherapy would eliminate malignant disease and reinfusion
      of the graft would then restore hematopoiesis. However, as the contribution of
      graft-versus-tumor effects to the success of allogeneic HCT was recognized over
      time, in an effort to exploit these, many investigators lowered the dose of
      radiation and chemotherapeutic agents in the preparative regimen. This resulted
      in a major paradigm shift, and consequently, the pool of eligible patients
      underwent a remarkable expansion. In this article, we provide a review of the
      definition of high-dose, reduced-intensity, and nonmyeloablative conditioning
      regimens, the most commonly used agents and combinations, and the evolution of
      some early regimens. We also provide a brief review of the toxicities associated
      with these regimens. 

PMID- 24914145
TI  - Structural biology at the European X-ray free-electron laser facility.
AB  - The European X-ray free-electron laser (XFEL) facility, under construction in the
      Hamburg region, will provide high-peak brilliance (greater than 10(33) photons s(
      1) mm(-2) mrad(-2) per 0.1% BW), ultrashort pulses (approx. 10 fs) of X-rays,
      with a high repetition rate (up to 27 000 pulses s(-1)) from 2016 onwards. The
      main features of this exceptional X-ray source, and the instrumentation
      developments necessary to exploit them fully, for application to a variety of
      scientific disciplines, are briefly summarized. In the case of structural
      biology, that has a central role in the scientific case of this new facility, the
      instruments and ancillary laboratories that are being planned and built within
      the baseline programme of the European XFEL and by consortia of users are also
      discussed. It is expected that the unique features of the source and the advanced
      features of the instrumentation will allow operation modes with more efficient
      use of sample materials, faster acquisition times, and conditions better
      approaching feasibility of single molecule imaging. 

PMID- 24914146
TI  - Diffraction before destruction.
AB  - X-ray free-electron lasers have opened up the possibility of structure
      determination of protein crystals at room temperature, free of radiation damage.
      The femtosecond-duration pulses of these sources enable diffraction signals to be
      collected from samples at doses of 1000 MGy or higher. The sample is vaporized by
      the intense pulse, but not before the scattering that gives rise to the
      diffraction pattern takes place. Consequently, only a single flash diffraction
      pattern can be recorded from a crystal, giving rise to the method of serial
      crystallography where tens of thousands of patterns are collected from individual
      crystals that flow across the beam and the patterns are indexed and aggregated
      into a set of structure factors. The high-dose tolerance and the many-crystal
      averaging approach allow data to be collected from much smaller crystals than
      have been examined at synchrotron radiation facilities, even from radiation
      sensitive samples. Here, we review the interaction of intense femtosecond X-ray
      pulses with materials and discuss the implications for structure determination.
      We identify various dose regimes and conclude that the strongest achievable
      signals for a given sample are attained at the highest possible dose rates, from
      highest possible pulse intensities. 

PMID- 24914147
TI  - Femtosecond crystallography of membrane proteins in the lipidic cubic phase.
AB  - Despite recent technological advances in heterologous expression, stabilization
      and crystallization of membrane proteins (MPs), their structural studies remain
      difficult and require new transformative approaches. During the past two years,
      crystallization in lipidic cubic phase (LCP) has started gaining a widespread
      acceptance, owing to the spectacular success in high-resolution structure
      determination of G protein-coupled receptors (GPCRs) and to the introduction of
      commercial instrumentation, tools and protocols. The recent appearance of X-ray
      free-electron lasers (XFELs) has enabled structure determination from
      substantially smaller crystals than previously possible with minimal effects of
      radiation damage, offering new exciting opportunities in structural biology. The
      unique properties of LCP material have been exploited to develop special
      protocols and devices that have established a new method of serial femtosecond
      crystallography of MPs in LCP (LCP-SFX). In this method, microcrystals are
      generated in LCP and streamed continuously inside the same media across the
      intersection with a pulsed XFEL beam at a flow rate that can be adjusted to
      minimize sample consumption. Pioneering studies that yielded the first room
      temperature GPCR structures, using a few hundred micrograms of purified protein,
      validate the LCP-SFX approach and make it attractive for structure determination
      of difficult-to-crystallize MPs and their complexes with interacting partners.
      Together with the potential of femtosecond data acquisition to interrogate
      unstable intermediate functional states of MPs, LCP-SFX holds promise to advance
      our understanding of this biomedically important class of proteins. 

PMID- 24914148
TI  - Observation of correlated X-ray scattering at atomic resolution.
AB  - Tools to study disordered systems with local structural order, such as proteins
      in solution, remain limited. Such understanding is essential for e.g. rational
      drug design. Correlated X-ray scattering (CXS) has recently attracted new
      interest as a way to leverage next-generation light sources to study such
      disordered matter. The CXS experiment measures angular correlations of the
      intensity caused by the scattering of X-rays from an ensemble of identical
      particles, with disordered orientation and position. Averaging over 15 496
      snapshot images obtained by exposing a sample of silver nanoparticles in solution
      to a micro-focused synchrotron radiation beam, we report on experimental efforts
      to obtain CXS signal from an ensemble in three dimensions. A correlation function
      was measured at wide angles corresponding to atomic resolution that matches
      theoretical predictions. These preliminary results suggest that other CXS
      experiments on disordered ensembles--such as proteins in solution--may be
      feasible in the future.

PMID- 24914149
TI  - Microcrystallization techniques for serial femtosecond crystallography using
      photosystem II from Thermosynechococcus elongatus as a model system.
AB  - Serial femtosecond crystallography (SFX) is a new emerging method, where X-ray
      diffraction data are collected from a fully hydrated stream of nano- or
      microcrystals of biomolecules in their mother liquor using high-energy, X-ray
      free-electron lasers. The success of SFX experiments strongly depends on the
      ability to grow large amounts of well-ordered nano/microcrystals of homogeneous
      size distribution. While methods to grow large single crystals have been
      extensively explored in the past, method developments to grow nano/microcrystals
      in sufficient amounts for SFX experiments are still in their infancy. Here, we
      describe and compare three methods (batch, free interface diffusion (FID) and FID
      centrifugation) for growth of nano/microcrystals for time-resolved SFX
      experiments using the large membrane protein complex photosystem II as a model
      system. 

PMID- 24914150
TI  - Opportunities and challenges for time-resolved studies of protein structural
      dynamics at X-ray free-electron lasers.
AB  - X-ray free-electron lasers (XFELs) are revolutionary X-ray sources. Their time
      structure, providing X-ray pulses of a few tens of femtoseconds in duration; and
      their extreme peak brilliance, delivering approximately 10(12) X-ray photons per
      pulse and facilitating sub-micrometre focusing, distinguish XFEL sources from
      synchrotron radiation. In this opinion piece, I argue that these properties of
      XFEL radiation will facilitate new discoveries in life science. I reason that
      time-resolved serial femtosecond crystallography and time-resolved wide angle X
      ray scattering are promising areas of scientific investigation that will be
      advanced by XFEL capabilities, allowing new scientific questions to be addressed
      that are not accessible using established methods at storage ring facilities.
      These questions include visualizing ultrafast protein structural dynamics on the
      femtosecond to picosecond time-scale, as well as time-resolved diffraction
      studies of non-cyclic reactions. I argue that these emerging opportunities will
      stimulate a renaissance of interest in time-resolved structural biochemistry. 

PMID- 24914151
TI  - Transmission electron microscopy as a tool for nanocrystal characterization pre-
      and post-injector.
AB  - Recent advancements at the Linac Coherent Light Source X-ray free-electron laser
      (XFEL) enabling successful serial femtosecond diffraction experiments using
      nanometre-sized crystals (NCs) have opened up the possibility of X-ray structure
      determination of proteins that produce only submicrometre crystals such as many
      membrane proteins. Careful crystal pre-characterization including compatibility
      testing of the sample delivery method is essential to ensure efficient use of the
      limited beamtime available at XFEL sources. This work demonstrates the utility of
      transmission electron microscopy for detecting and evaluating NCs within the
      carrier solutions of liquid injectors. The diffraction quality of these crystals
      may be assessed by examining the crystal lattice and by calculating the fast
      Fourier transform of the image. Injector reservoir solutions, as well as
      solutions collected post-injection, were evaluated for three types of protein NCs
      (i) the membrane protein PTHR1, (ii) the multi-protein complex Pol II-GFP and
      (iii) the soluble protein lysozyme. Our results indicate that the concentration
      and diffraction quality of NCs, particularly those with high solvent content and
      sensitivity to mechanical manipulation may be affected by the delivery process. 

PMID- 24914152
TI  - The Mn4Ca photosynthetic water-oxidation catalyst studied by simultaneous X-ray
      spectroscopy and crystallography using an X-ray free-electron laser.
AB  - The structure of photosystem II and the catalytic intermediate states of the
      Mn4CaO5 cluster involved in water oxidation have been studied intensively over
      the past several years. An understanding of the sequential chemistry of light
      absorption and the mechanism of water oxidation, however, requires a new approach
      beyond the conventional steady-state crystallography and X-ray spectroscopy at
      cryogenic temperatures. In this report, we present the preliminary progress using
      an X-ray free-electron laser to determine simultaneously the light-induced
      protein dynamics via crystallography and the local chemistry that occurs at the
      catalytic centre using X-ray spectroscopy under functional conditions at room
      temperature.

PMID- 24914153
TI  - Coherent convergent-beam time-resolved X-ray diffraction.
AB  - The use of coherent X-ray lasers for structural biology allows the use of
      nanometre diameter X-ray beams with large beam divergence. Their application to
      the structure analysis of protein nanocrystals and single particles raises new
      challenges and opportunities. We discuss the form of these coherent convergent
      beam (CCB) hard X-ray diffraction patterns and their potential use for time
      resolved crystallography, normally achieved by Laue (polychromatic) diffraction,
      for which the monochromatic laser radiation of a free-electron X-ray laser is
      unsuitable. We discuss the possibility of obtaining single-shot, angle-integrated
      rocking curves from CCB patterns, and the dependence of the resulting patterns on
      the focused beam coordinate when the beam diameter is larger or smaller than a
      nanocrystal, or smaller than one unit cell. We show how structure factor phase
      information is provided at overlapping interfering orders and how a common phase
      origin between different shots may be obtained. Their use in refinement of the
      phase-sensitive intensity between overlapping orders is suggested. 

PMID- 24914154
TI  - High-resolution structure of viruses from random diffraction snapshots.
AB  - The advent of the X-ray free-electron laser (XFEL) has made it possible to record
      diffraction snapshots of biological entities injected into the X-ray beam before
      the onset of radiation damage. Algorithmic means must then be used to determine
      the snapshot orientations and thence the three-dimensional structure of the
      object. Existing Bayesian approaches are limited in reconstruction resolution
      typically to 1/10 of the object diameter, with the computational expense
      increasing as the eighth power of the ratio of diameter to resolution. We present
      an approach capable of exploiting object symmetries to recover three-dimensional
      structure to high resolution, and thus reconstruct the structure of the satellite
      tobacco necrosis virus to atomic level. Our approach offers the highest
      reconstruction resolution for XFEL snapshots to date and provides a potentially
      powerful alternative route for analysis of data from crystalline and nano
      crystalline objects. 

PMID- 24914155
TI  - A minimal view of single-particle imaging with X-ray lasers.
AB  - The ability to serially interrogate single biomolecules with femtosecond X-ray
      pulses from free-electron lasers has ushered in the possibility of determining
      the three-dimensional structure of biomolecules without crystallization. However,
      the complexity of imaging a sample's structure from very many of its noisy and
      incomplete diffraction data can be daunting. In this review, we introduce a
      simple analogue of this imaging workflow, use it to describe a structure
      reconstruction algorithm based on the expectation maximization principle, and
      consider the effects of extraneous noise. Such a minimal model can aid experiment
      and algorithm design in future studies. 

PMID- 24914156
TI  - The correlation of single-particle diffraction patterns as a continuous function
      of particle orientation.
AB  - A statistical model for X-ray scattering of a non-periodic sample to high angles
      is introduced. It is used to calculate analytically the correlation of distinct
      diffraction measurements of a particle as a continuous function of particle
      orientation. Diffraction measurements with shot-noise are also considered. This
      theory provides a general framework for a deeper understanding of single particle
      imaging techniques used at X-ray free-electron lasers. Many of these techniques
      use correlations as a measure of diffraction-pattern similarity in order to
      determine properties of the sample, such as particle orientation. 

PMID- 24914157
TI  - Post-refinement method for snapshot serial crystallography.
AB  - A post-refinement procedure has been devised for 'snapshot' diffraction data
      consisting entirely of partially recorded reflections, each diffraction pattern
      from a crystal in an orientation unrelated to the others. Initial estimates of
      the diffraction geometry are used to calculate initial partialities, which are
      then used to scale the entire dataset together to produce initial estimates of
      the fully integrated intensities. The geometrical parameters for each pattern are
      then refined to maximize the agreement between these estimates and the calculated
      intensities in each pattern, and the procedure repeated iteratively. The
      performance of the procedure was investigated using simulated data and found to
      yield a significant improvement in the data quality. 

PMID- 24914158
TI  - Phasing coherently illuminated nanocrystals bounded by partial unit cells.
AB  - With the use of highly coherent femtosecond X-ray pulses from a free-electron
      laser, it is possible to record protein nanocrystal diffraction patterns with far
      more information than is present in conventional crystallographic diffraction
      data. It has been suggested that diffraction phases may be retrieved from such
      data via iterative algorithms, without the use of a priori information and
      without restrictions on resolution. Here, we investigate the extension of this
      approach to nanocrystals with edge terminations that produce partial unit cells,
      and hence cannot be described by a common repeating unit cell. In this situation,
      the phase problem described in previous work must be reformulated. We demonstrate
      an approximate solution to this phase problem for crystals with random edge
      terminations. 

PMID- 24914159
TI  - Deducing fast electron density changes in randomly orientated uncrystallized
      biomolecules in a pump-probe experiment.
AB  - We propose a method for deducing time-resolved structural changes in
      uncrystallized biomolecules in solution. The method relies on measuring the
      angular correlations of the intensities, when averaged over a large number of
      diffraction patterns from randomly oriented biomolecules in solution in a liquid
      solvent. The experiment is somewhat like a pump-probe version of an experiment on
      small angle X-ray scattering, except that the data expected by the algorithm are
      not just the radial variation of the averaged intensities. The differences of
      these correlation functions as measured from a photoexcited and dark structure
      enable the direct calculation of the difference electron density with a knowledge
      of only the dark structure. We exploit a linear relation we derive between the
      difference in these correlation functions and the difference electron density,
      applicable for small structural changes. 

PMID- 24914160
TI  - Mapping the continuous reciprocal space intensity distribution of X-ray serial
      crystallography.
AB  - Serial crystallography using X-ray free-electron lasers enables the collection of
      tens of thousands of measurements from an equal number of individual crystals,
      each of which can be smaller than 1 um in size. This manuscript describes an
      alternative way of handling diffraction data recorded by serial femtosecond
      crystallography, by mapping the diffracted intensities into three-dimensional
      reciprocal space rather than integrating each image in two dimensions as in the
      classical approach. We call this procedure 'three-dimensional merging'. This
      procedure retains information about asymmetry in Bragg peaks and diffracted
      intensities between Bragg spots. This intensity distribution can be used to
      extract reflection intensities for structure determination and opens up novel
      avenues for post-refinement, while observed intensity between Bragg peaks and
      peak asymmetry are of potential use in novel direct phasing strategies. 

PMID- 24914161
TI  - Two-dimensional imaging detectors for structural biology with X-ray lasers.
AB  - Our ability to harness the advances in microelectronics over the past decade(s)
      for X-ray detection has resulted in significant improvements in the state of the
      art. Biology with X-ray free-electron lasers present daunting detector
      challenges: all of the photons arrive at the same time, and individual high peak
      power pulses must be read out shot-by-shot. Direct X-ray detection in silicon
      pixel detectors--monolithic or hybrid--are the standard for XFELs today. For
      structural biology, improvements are needed for today's 10-100 Hz XFELs, and
      further improvements are required for tomorrow's 10+ kHz XFELs. This article will
      discuss detector challenges, why they arise and ways to overcome them, along with
      the current state of the art.

PMID- 24914162
TI  - Singular value decomposition as a tool for background corrections in time
      resolved XFEL scattering data.
AB  - The development of new X-ray light sources, XFELs, with unprecedented time and
      brilliance characteristics has led to the availability of very large datasets
      with high time resolution and superior signal strength. The chaotic nature of the
      emission processes in such sources as well as entirely novel detector demands has
      also led to significant challenges in terms of data analysis. This paper
      describes a heuristic approach to datasets where spurious background
      contributions of a magnitude similar to (or larger) than the signal of interest
      prevents conventional analysis approaches. The method relies on singular-value
      decomposition of no-signal subsets of acquired datasets in combination with model
      inputs and appears generally applicable to time-resolved X-ray diffuse scattering
      experiments. 

PMID- 24914163
TI  - Liquid sample delivery techniques for serial femtosecond crystallography.
AB  - X-ray free-electron lasers overcome the problem of radiation damage in protein
      crystallography and allow structure determination from micro- and nanocrystals at
      room temperature. To ensure that consecutive X-ray pulses do not probe previously
      exposed crystals, the sample needs to be replaced with the X-ray repetition rate,
      which ranges from 120 Hz at warm linac-based free-electron lasers to 1 MHz at
      superconducting linacs. Liquid injectors are therefore an essential part of a
      serial femtosecond crystallography experiment at an X-ray free-electron laser.
      Here, we compare different techniques of injecting microcrystals in solution into
      the pulsed X-ray beam in vacuum. Sample waste due to mismatch of the liquid flow
      rate to the X-ray repetition rate can be addressed through various techniques. 

PMID- 24914164
TI  - In vivo crystallography at X-ray free-electron lasers: the next generation of
      structural biology?
AB  - The serendipitous discovery of the spontaneous growth of protein crystals inside
      cells has opened the field of crystallography to chemically unmodified samples
      directly available from their natural environment. On the one hand, through in
      vivo crystallography, protocols for protein crystal preparation can be highly
      simplified, although the technique suffers from difficulties in sampling,
      particularly in the extraction of the crystals from the cells partly due to their
      small sizes. On the other hand, the extremely intense X-ray pulses emerging from
      X-ray free-electron laser (XFEL) sources, along with the appearance of serial
      femtosecond crystallography (SFX) is a milestone for radiation damage-free
      protein structural studies but requires micrometre-size crystals. The combination
      of SFX with in vivo crystallography has the potential to boost the applicability
      of these techniques, eventually bringing the field to the point where in vitro
      sample manipulations will no longer be required, and direct imaging of the
      crystals from within the cells will be achievable. To fully appreciate the
      diverse aspects of sample characterization, handling and analysis, SFX
      experiments at the Japanese SPring-8 angstrom compact free-electron laser were
      scheduled on various types of in vivo grown crystals. The first experiments have
      demonstrated the feasibility of the approach and suggest that future in vivo
      crystallography applications at XFELs will be another alternative to nano
      crystallography. 

PMID- 24914165
TI  - Aspects of direct phasing in femtosecond nanocrystallography.
AB  - X-ray free-electron laser diffraction patterns from protein nanocrystals provide
      information on the diffracted amplitudes between the Bragg reflections, offering
      the possibility of direct phase retrieval without the use of ancillary
      experimental data. Proposals for implementing direct phase retrieval are
      reviewed. These approaches are limited by the signal-to-noise levels in the data
      and the presence of different and incomplete unit cells in the nanocrystals. The
      effects of low signal to noise can be ameliorated by appropriate selection of the
      intensity data samples that are used. The effects of incomplete unit cells may be
      small in some cases, and a unique solution is likely if there are four or fewer
      molecular orientations in the unit cell. 

PMID- 24914166
TI  - 7 A resolution in protein two-dimensional-crystal X-ray diffraction at Linac
      Coherent Light Source.
AB  - Membrane proteins arranged as two-dimensional crystals in the lipid environment
      provide close-to-physiological structural information, which is essential for
      understanding the molecular mechanisms of protein function. Previously, X-ray
      diffraction from individual two-dimensional crystals did not represent a suitable
      investigational tool because of radiation damage. The recent availability of
      ultrashort pulses from X-ray free-electron lasers (XFELs) has now provided a
      means to outrun the damage. Here, we report on measurements performed at the
      Linac Coherent Light Source XFEL on bacteriorhodopsin two-dimensional crystals
      mounted on a solid support and kept at room temperature. By merging data from
      about a dozen single crystal diffraction images, we unambiguously identified the
      diffraction peaks to a resolution of 7 A, thus improving the observable
      resolution with respect to that achievable from a single pattern alone. This
      indicates that a larger dataset will allow for reliable quantification of peak
      intensities, and in turn a corresponding increase in the resolution. The
      presented results pave the way for further XFEL studies on two-dimensional
      crystals, which may include pump-probe experiments at subpicosecond time
      resolution. 

PMID- 24914167
TI  - Conformations of macromolecules and their complexes from heterogeneous datasets.
AB  - We describe a new generation of algorithms capable of mapping the structure and
      conformations of macromolecules and their complexes from large ensembles of
      heterogeneous snapshots, and demonstrate the feasibility of determining both
      discrete and continuous macromolecular conformational spectra. These algorithms
      naturally incorporate conformational heterogeneity without resort to sorting and
      classification, or prior knowledge of the type of heterogeneity present. They are
      applicable to single-particle diffraction and image datasets produced by X-ray
      lasers and cryo-electron microscopy, respectively, and particularly suitable for
      systems not easily amenable to purification or crystallization. 

PMID- 24914168
TI  - Time-resolved crystallography and protein design: signalling photoreceptors and
      optogenetics.
AB  - Time-resolved X-ray crystallography and solution scattering have been
      successfully conducted on proteins on time-scales down to around 100 ps, set by
      the duration of the hard X-ray pulses emitted by synchrotron sources. The advent
      of hard X-ray free-electron lasers (FELs), which emit extremely intense, very
      brief, coherent X-ray pulses, opens the exciting possibility of time-resolved
      experiments with femtosecond time resolution on macromolecular structure, in both
      single crystals and solution. The X-ray pulses emitted by an FEL differ greatly
      in many properties from those emitted by a synchrotron, in ways that at first
      glance make time-resolved measurements of X-ray scattering with the required
      accuracy extremely challenging. This opens up several questions which I consider
      in this brief overview. Are there likely to be chemically and biologically
      interesting structural changes to be revealed on the femtosecond time-scale? How
      shall time-resolved experiments best be designed and conducted to exploit the
      properties of FELs and overcome challenges that they pose? To date, fast time
      resolved reactions have been initiated by a brief laser pulse, which obviously
      requires that the system under study be light-sensitive. Although this is true
      for proteins of the visual system and for signalling photoreceptors, it is not
      naturally the case for most interesting biological systems. To generate more
      biological targets for time-resolved study, can this limitation be overcome by
      optogenetic, chemical or other means? 

PMID- 24914169
TI  - Methods development for diffraction and spectroscopy studies of metalloenzymes at
      X-ray free-electron lasers.
AB  - X-ray free-electron lasers (XFELs) open up new possibilities for X-ray
      crystallographic and spectroscopic studies of radiation-sensitive biological
      samples under close to physiological conditions. To facilitate these new X-ray
      sources, tailored experimental methods and data-processing protocols have to be
      developed. The highly radiation-sensitive photosystem II (PSII) protein complex
      is a prime target for XFEL experiments aiming to study the mechanism of light
      induced water oxidation taking place at a Mn cluster in this complex. We
      developed a set of tools for the study of PSII at XFELs, including a new liquid
      jet based on electrofocusing, an energy dispersive von Hamos X-ray emission
      spectrometer for the hard X-ray range and a high-throughput soft X-ray
      spectrometer based on a reflection zone plate. While our immediate focus is on
      PSII, the methods we describe here are applicable to a wide range of
      metalloenzymes. These experimental developments were complemented by a new
      software suite, cctbx.xfel. This software suite allows for near-real-time
      monitoring of the experimental parameters and detector signals and the detailed
      analysis of the diffraction and spectroscopy data collected by us at the Linac
      Coherent Light Source, taking into account the specific characteristics of data
      measured at an XFEL. 

PMID- 24914171
TI  - Teenagers are using sunbeds less since ban but are still getting burnt.

PMID- 24914170
TI  - 'Hit and run' serial femtosecond crystallography of a membrane kinase in the
      lipid cubic phase.
AB  - The lipid-based bicontinuous cubic mesophase is a nanoporous membrane mimetic
      with applications in areas that include medicine, personal care products, foods
      and the basic sciences. An application of particular note concerns it use as a
      medium in which to grow crystals of membrane proteins for structure determination
      by X-ray crystallography. At least two variations of the mesophase exist. One is
      the highly viscous cubic phase, which has well developed long-range order. The
      other so-called sponge phase is considerably more fluid and lacks long-range
      order. The sponge phase has recently been shown to be a convenient vehicle for
      delivering microcrystals of membrane proteins to an X-ray free-electron laser
      beam for serial femtosecond crystallography (SFX). Unfortunately, the sponge
      phase approach calls for large amounts of protein that are not always available
      in the case of membrane proteins. The cubic phase offers the advantage of
      requiring significantly less protein for SFX but comes with its own challenges.
      Here, we describe the physico-chemical bases for these challenges, solutions to
      them and prospects for future uses of lipidic mesophases in the SFX arena. 

PMID- 24914172
TI  - Challenges in mucosal vaccines for the control of infectious diseases.
AB  - The mucosal surface is the largest route through which pathogens enter the human
      body. To control the outbreak of mucosal infectious diseases, we must use our
      knowledge of the mucosal immune system to create vaccines that elicit protective
      mucosal and systemic immunity. Mucosal vaccines have advantages over traditional
      injectable vaccines in that they not only induce effective mucosal immune
      responses, but they also do not cause physical or psychological discomfort.
      Mucosal vaccines currently licensed for human use include oral vaccines against
      Vibrio cholerae, Salmonella typhi, poliovirus and rotavirus, and nasal vaccines
      against influenza virus. To further improve the existing vaccines, it will be
      necessary to develop novel vaccine production, storage and delivery systems
      through innovative strategies derived from interdisciplinary scientific research.
      Our accumulated knowledge of the innate and acquired arms of the mucosal immune
      system and the recent scientific and technical advancements in the fields of
      molecular biology, plant biology, bio-engineering and chemical engineering,
      genome biology and systems biology have created a unique research and development
      platform for the development of the next generation of mucosal vaccines. This
      review summarizes the current perspectives and future directions of mucosal
      vaccine development with emphasis on oral and nasal vaccines for the control of
      infectious diseases. 

PMID- 24914173
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health.

PMID- 24914174
TI  - House of Lords is to consider bill on assisted suicide.

PMID- 24914175
TI  - How Do You Know if You Are in La La Land?

PMID- 24914177
TI  - Detecting the psychosis prodrome across high-risk populations using
      neuroanatomical biomarkers.
AB  - To date, the MRI-based individualized prediction of psychosis has only been
      demonstrated in single-site studies. It remains unclear if MRI biomarkers
      generalize across different centers and MR scanners and represent accurate
      surrogates of the risk for developing this devastating illness. Therefore, we
      assessed whether a MRI-based prediction system identified patients with a later
      disease transition among 73 clinically defined high-risk persons recruited at two
      different early recognition centers. Prognostic performance was measured using
      cross-validation, independent test validation, and Kaplan-Meier survival
      analysis. Transition outcomes were correctly predicted in 80% of test cases
      (sensitivity: 76%, specificity: 85%, positive likelihood ratio: 5.1). Thus, given
      a 54-month transition risk of 45% across both centers, MRI-based predictors
      provided a 36%-increase of prognostic certainty. After stratifying individuals
      into low-, intermediate-, and high-risk groups using the predictor's decision
      score, the high- vs low-risk groups had median psychosis-free survival times of 5
      vs 51 months and transition rates of 88% vs 8%. The predictor's decision function
      involved gray matter volume alterations in prefrontal, perisylvian, and
      subcortical structures. Our results support the existence of a cross-center
      neuroanatomical signature of emerging psychosis enabling individualized risk
      staging across different high-risk populations. Supplementary results revealed
      that (1) potentially confounding between-site differences were effectively
      mitigated using statistical correction methods, and (2) the detection of the
      prodromal signature considerably depended on the available sample sizes. These
      observations pave the way for future multicenter studies, which may ultimately
      facilitate the neurobiological refinement of risk criteria and personalized
      preventive therapies based on individualized risk profiling tools. 

PMID- 24914176
TI  - Progressive reduction of visual P300 amplitude in patients with first-episode
      schizophrenia: an ERP study.
AB  - OBJECTIVE: To understand the underlying dynamic neurophysiological changes over
      the course of schizophrenia, it is important to study subjects longitudinally
      from the early stage of the illness. We previously reported that visual P300 was
      already impaired in patients with first-episode schizophrenia (FESZ). This study
      demonstrates how the visual P300, as well as earlier components P1, N1, and N200,
      changed at the 1-year follow-up after their initial measurement. METHODS: Visual
      ERPs were recorded with the same experimental paradigm and acquisition protocol
      at both time points in FESZ (n = 18) and healthy comparison subjects (n = 24).
      Participants silently counted infrequent target stimuli ("x") amid standard
      stimuli ("y") presented on the screen while the 64-channel electroencephalogram
      was recorded. RESULTS: FESZ showed smaller visual P300, N200, P1 (trend level)
      amplitude and delayed P300 and N1 latency at both time points; however, only P300
      showed progressive amplitude reduction over the course of the illness at 1-year
      follow-up. P300 latency did not change over time in either group. FESZ showed
      significantly reduced Spatial Span total score at both time points, and there was
      a significant negative correlation between P300 peak amplitude and the Brief
      Psychiatric Rating Scale positive symptom score at baseline. CONCLUSION: These
      data show progressive P300 amplitude reduction in response to visual stimuli in
      the early stage of schizophrenia. These visual P300 findings support the concept
      of progression of schizophrenia, suggesting the usefulness of the visual P300 as
      a biological marker of progression.

PMID- 24914178
TI  - Transcription of the lysine-2,3-aminomutase gene in the kam locus of Bacillus
      thuringiensis subsp. kurstaki HD73 is controlled by both sigma54 and sigmaK
      factors.
AB  - Lysine 2,3-aminomutase (KAM; EC 5.4.3.2) catalyzes the interconversion of l
      lysine and l-beta-lysine. The transcription and regulation of the kam locus,
      including lysine-2,3-aminomutase-encoding genes, in Bacillus thuringiensis were
      analyzed in this study. Reverse transcription-PCR (RT-PCR) analysis revealed that
      this locus forms two operons: yodT (yodT-yodS-yodR-yodQ-yodP-kamR) and kamA (kamA
      yokU-yozE). The transcriptional start sites (TSSs) of the kamA gene were
      determined using 5' rapid amplification of cDNA ends (RACE). A typical -12/-24
      sigma(54) binding site was identified in the promoter PkamA, which is located
      upstream of the kamA gene TSS. A beta-galactosidase assay showed that PkamA,
      which directs the transcription of the kamA operon, is controlled by the
      sigma(54) factor and is activated through the sigma(54)-dependent transcriptional
      regulator KamR. The kamA operon is also controlled by sigma(K) and regulated by
      the GerE protein in the late stage of sporulation. kamR and kamA mutants were
      prepared by homologous recombination to examine the role of the kam locus. The
      results showed that the sporulation rate in B. thuringiensis HD(DeltakamR) was
      slightly decreased compared to that in HD73, whereas that in HD(DeltakamA) was
      similar to that in HD73. This means that other genes regulated by KamR are
      important for sporulation. 

PMID- 24914179
TI  - Leucine-responsive regulatory protein Lrp and PapI homologues influence phase
      variation of CS31A fimbriae.
AB  - CS31A, a K88-related surface antigen specified by the clp operon, is a member of
      the type P family of adhesive factors and plays a key role in the establishment
      of disease caused by septicemic and enterotoxigenic Escherichia coli strains. Its
      expression is under the control of methylation-dependent transcriptional
      regulation, for which the leucine-responsive regulatory protein (Lrp) is
      essential. CS31A is preferentially in the OFF state and exhibits distinct
      regulatory features compared to the regulation of other P family members. In the
      present study, surface plasmon resonance and DNase I protection assays showed
      that Lrp binds to the distal moiety of the clp regulatory region with low
      micromolar affinity compared to its binding to the proximal moiety, which
      exhibits stronger, nanomolar affinity. The complex formation was also influenced
      by the addition of PapI or FooI, which increased the affinity of Lrp for the clp
      distal and proximal regions and was required to induce phase variation. The
      influence of PapI or FooI, however, was predominantly associated with a more
      complete shutdown of clp expression, in contrast to what has previously been
      observed with AfaF (a PapI ortholog). Taken together, these results suggest that
      the preferential OFF state observed in CS31A cells is mainly due to the weak
      interaction of the leucine-responsive regulatory protein with the clp distal
      region and that the PapI homolog favors the OFF phase. Within the large
      repertoire of fimbrial variants in the P family, our study illustrates that
      having a fimbrial operon that lacks its own PapI ortholog allows it to be more
      flexibly regulated by other orthologs in the cell. 

PMID- 24914180
TI  - Benzylidene acylhydrazides inhibit chlamydial growth in a type III secretion- and
      iron chelation-independent manner.
AB  - Chlamydiae are widespread Gram-negative pathogens of humans and animals.
      Salicylidene acylhydrazides, developed as inhibitors of type III secretion system
      (T3SS) in Yersinia spp., have an inhibitory effect on chlamydial infection.
      However, these inhibitors also have the capacity to chelate iron, and it is
      possible that their antichlamydial effects are caused by iron starvation.
      Therefore, we have explored the modification of salicylidene acylhydrazides with
      the goal to uncouple the antichlamydial effect from iron starvation. We
      discovered that benzylidene acylhydrazides, which cannot chelate iron, inhibit
      chlamydial growth. Biochemical and genetic analyses suggest that the derivative
      compounds inhibit chlamydiae through a T3SS-independent mechanism. Four single
      nucleotide polymorphisms were identified in a Chlamydia muridarum variant
      resistant to benzylidene acylhydrazides, but it may be necessary to segregate the
      mutations to differentiate their roles in the resistance phenotype. Benzylidene
      acylhydrazides are well tolerated by host cells and probiotic vaginal
      Lactobacillus species and are therefore of potential therapeutic value. 

PMID- 24914181
TI  - The Ctp type IVb pilus locus of Agrobacterium tumefaciens directs formation of
      the common pili and contributes to reversible surface attachment.
AB  - Agrobacterium tumefaciens can adhere to plant tissues and abiotic surfaces and
      forms biofilms. Cell surface appendages called pili play an important role in
      adhesion and biofilm formation in diverse bacterial systems. The A. tumefaciens
      C58 genome sequence revealed the presence of the ctpABCDEFGHI genes (cluster of
      type IV pili; Atu0216 to Atu0224), homologous to tad-type pilus systems from
      several bacteria, including Aggregatibacter actinomycetemcomitans and Caulobacter
      crescentus. These systems fall into the type IVb pilus group, which can function
      in bacterial adhesion. Transmission electron microscopy of A. tumefaciens
      revealed the presence of filaments, significantly thinner than flagella and often
      bundled, associated with cell surfaces and shed into the external milieu. In
      frame deletion mutations of all of the ctp genes, with the exception of ctpF,
      resulted in nonpiliated derivatives. Mutations in ctpA (a pilin homologue), ctpB,
      and ctpG decreased early attachment and biofilm formation. The adherence of the
      ctpA mutant could be restored by ectopic expression of the paralogous pilA gene.
      The DeltactpA DeltapilA double pilin mutant displayed a diminished biovolume and
      lower biofilm height than the wild type under flowing conditions. Surprisingly,
      however, the ctpCD, ctpE, ctpF, ctpH, and ctpI mutants formed normal biofilms and
      showed enhanced reversible attachment. In-frame deletion of the ctpA pilin gene
      in the ctpCD, ctpE, ctpF, ctpH, and ctpI mutants caused the same attachment
      deficient phenotype as the ctpA single mutant. Collectively, these findings
      indicate that the ctp locus is involved in pilus assembly and that nonpiliated
      mutants, which retain the CtpA pilin, are proficient in attachment and adherence.

PMID- 24914182
TI  - Identification of three noncontiguous regions on Bacillus anthracis plasmid pXO1
      that are important for its maintenance.
AB  - Bacillus anthracis pXO1 minireplicon (MR) plasmid consisting of open reading
      frames (ORFs) GBAA_pXO1_0020 to GBAA_pXO1_0023 is not stably maintained in B.
      anthracis, whereas the full-size parent pXO1 plasmid (having 181,677 bp and 217
      ORFs) is extremely stable under the same growth conditions. Two genetic tools
      developed for DNA manipulation in B. anthracis (Cre-loxP and Flp-FRT systems)
      were used to identify pXO1 regions important for plasmid stability. We localized
      a large segment of pXO1 that enables stable plasmid maintenance during vegetative
      growth. Further genetic analysis identified three genes that are necessary for
      pXO1 maintenance: amsP (GBAA_pXO1_0069), minP (GBAA_pXO1_0082), and sojP
      (GBAA_pXO1_0084). Analysis of conserved domains in the corresponding proteins
      indicated that only AmsP (activator of maintenance system of pXO1) is predicted
      to bind DNA, due to its strong helix-turn-helix domain. Two conserved domains
      were found in the MinP protein (Min protein from pXO1): an N-terminal domain
      having some similarity to the B. anthracis septum site-determining protein MinD
      and a C-terminal domain that resembles a baculovirus single-stranded-DNA-binding
      protein. The SojP protein (Soj from pXO1) contains putative Walker box motifs and
      belongs to the ParA family of ATPases. No sequences encoding other components of
      type I plasmid partition systems, namely, cis-acting centromere parS and its
      binding ParB protein, were identified within the pXO1 genome. A model describing
      the role of the MinP protein in pXO1 distribution between daughter cells is
      proposed. 

PMID- 24914183
TI  - TraK and TraB are conserved outer membrane proteins of the Neisseria gonorrhoeae
      Type IV secretion system and are expressed at low levels in wild-type cells.
AB  - Neisseria gonorrhoeae uses a type IV secretion system (T4SS) to secrete
      chromosomal DNA into the medium, and this DNA is effective in transforming other
      gonococci via natural transformation. In addition, the T4SS is important in the
      initial stages of biofilm development and mediates intracellular iron uptake in
      the absence of TonB. To better understand the mechanism of type IV secretion in
      N. gonorrhoeae, we examined the expression levels and localization of two
      predicted T4SS outer membrane proteins, TraK and TraB, in the wild-type strain as
      well as in overexpression strains and in a strain lacking all of the T4SS
      proteins. Despite very low sequence similarity to known homologues, TraB (VirB10
      homolog) and TraK (VirB9 homolog) localized similarly to related proteins in
      other systems. Additionally, we found that TraV (a VirB7 homolog) interacts with
      TraK, as in other T4SSs. However, unlike in other systems, neither TraK nor TraB
      required the presence of other T4SS components for proper localization. Unlike
      other gonococcal T4SS proteins we have investigated, protein levels of the outer
      membrane proteins TraK and TraB were extremely low in wild-type cells and were
      undetectable by Western blotting unless overexpressed or tagged with a FLAG3
      triple-epitope tag. Localization of TraK-FLAG3 in otherwise wild-type cells using
      immunogold electron microscopy of thin sections revealed a single gold particle
      on some cells. These results suggest that the gonococcal T4SS may be present in
      single copy per cell and that small amounts of T4SS proteins TraK and TraB are
      sufficient for DNA secretion. 

PMID- 24914184
TI  - GneZ, a UDP-GlcNAc 2-epimerase, is required for S-layer assembly and vegetative
      growth of Bacillus anthracis.
AB  - Bacillus anthracis, the causative agent of anthrax, forms an S-layer atop its
      peptidoglycan envelope and displays S-layer proteins and Bacillus S-layer
      associated (BSL) proteins with specific functions to support cell separation of
      vegetative bacilli and growth in infected mammalian hosts. S-layer and BSL
      proteins bind via the S-layer homology (SLH) domain to the pyruvylated secondary
      cell wall polysaccharide (SCWP) with the repeat structure [->4)-beta-ManNAc-(1
      >4)-beta-GlcNAc-(1->6)-alpha-GlcNAc-(1->]n, where alpha-GlcNAc and beta-GlcNAc
      are substituted with two and one galactosyl residues, respectively. B. anthracis
      gneY (BAS5048) and gneZ (BAS5117) encode nearly identical UDP-GlcNAc 2-epimerase
      enzymes that catalyze the reversible conversion of UDP-GlcNAc and UDP-ManNAc. UDP
      GlcNAc 2-epimerase enzymes have been shown to be required for the attachment of
      the phage lysin PlyG with the bacterial envelope and for bacterial growth. Here,
      we asked whether gneY and gneZ are required for the synthesis of the pyruvylated
      SCWP and for S-layer assembly. We show that gneZ, but not gneY, is required for
      B. anthracis vegetative growth, rod cell shape, S-layer assembly, and synthesis
      of pyruvylated SCWP. Nevertheless, inducible expression of gneY alleviated all
      the defects associated with the gneZ mutant. In contrast to vegetative growth,
      neither germination of B. anthracis spores nor the formation of spores in mother
      cells required UDP-GlcNAc 2-epimerase activity. 

PMID- 24914185
TI  - A model for the evolution of biological specificity: a cross-reacting DNA-binding
      protein causes plasmid incompatibility.
AB  - Few biological systems permit rigorous testing of how changes in DNA sequence
      give rise to adaptive phenotypes. In this study, we sought a simplified
      experimental system with a detailed understanding of the genotype-to-phenotype
      relationship that could be altered by environmental perturbations. We focused on
      plasmid fitness, i.e., the ability of plasmids to be stably maintained in a
      bacterial population, which is dictated by the plasmid's replication and
      segregation machinery. Although plasmid replication depends on host proteins, the
      type II plasmid partitioning (Par) machinery is entirely plasmid encoded and
      relies solely on three components: parC, a centromere-like DNA sequence, ParR, a
      DNA-binding protein that interacts with parC, and ParM, which forms actin-like
      filaments that push two plasmids away from each other at cell division.
      Interactions between the Par operons of two related plasmids can cause
      incompatibility and the reduced transmission of one or both plasmids. We have
      identified segregation-dependent plasmid incompatibility between the highly
      divergent Par operons of plasmids pB171 and pCP301. Genetic and biochemical
      studies revealed that the incompatibility is due to the functional promiscuity of
      the DNA-binding protein ParRpB171, which interacts with both parC DNA sequences
      to direct plasmid segregation, indicating that the lack of DNA binding
      specificity is detrimental to plasmid fitness in this environment. This study
      therefore successfully utilized plasmid segregation to dissect the molecular
      interactions between genotype, phenotype, and fitness. 

PMID- 24914186
TI  - Error-prone processing of apurinic/apyrimidinic (AP) sites by PolX underlies a
      novel mechanism that promotes adaptive mutagenesis in Bacillus subtilis.
AB  - In growing cells, apurinic/apyrimidinic (AP) sites generated spontaneously or
      resulting from the enzymatic elimination of oxidized bases must be processed by
      AP endonucleases before they compromise cell integrity. Here, we investigated how
      AP sites and the processing of these noncoding lesions by the AP endonucleases
      Nfo, ExoA, and Nth contribute to the production of mutations (hisC952, metB5, and
      leuC427) in starved cells of the Bacillus subtilis YB955 strain. Interestingly,
      cells from this strain that were deficient for Nfo, ExoA, and Nth accumulated a
      greater amount of AP sites in the stationary phase than during exponential
      growth. Moreover, under growth-limiting conditions, the triple nfo exoA nth
      knockout strain significantly increased the amounts of adaptive his, met, and leu
      revertants produced by the B. subtilis YB955 parental strain. Of note, the number
      of stationary-phase-associated reversions in the his, met, and leu alleles
      produced by the nfo exoA nth strain was significantly decreased following
      disruption of polX. In contrast, during growth, the reversion rates in the three
      alleles tested were significantly increased in cells of the nfo exoA nth knockout
      strain deficient for polymerase X (PolX). Therefore, we postulate that adaptive
      mutations in B. subtilis can be generated through a novel mechanism mediated by
      error-prone processing of AP sites accumulated in the stationary phase by the
      PolX DNA polymerase. 

PMID- 24914188
TI  - Selection of dinB alleles suppressing survival loss upon dinB overexpression in
      Escherichia coli.
AB  - Escherichia coli strains overproducing DinB undergo survival loss; however, the
      mechanisms regulating this phenotype are poorly understood. Here we report a
      genetic selection revealing DinB residues essential to effect this loss-of
      survival phenotype. The selection uses strains carrying both an antimutator
      allele of DNA polymerase III (Pol III) alpha-subunit (dnaE915) and either
      chromosomal or plasmid-borne dinB alleles. We hypothesized that dnaE915 cells
      would respond to DinB overproduction differently from dnaE(+) cells because the
      dnaE915 allele is known to have an altered genetic interaction with dinB(+)
      compared to its interaction with dnaE(+). Notably, we observe a loss-of-survival
      phenotype in dnaE915 strains with either a chromosomal catalytically inactive
      dinB(D103N) allele or a low-copy-number plasmid-borne dinB(+) upon DNA damage
      treatment. Furthermore, we find that the loss-of-survival phenotype occurs
      independently of DNA damage treatment in a dnaE915 strain expressing the
      catalytically inactive dinB(D103N) allele from a low-copy-number plasmid. The
      selective pressure imposed resulted in suppressor mutations that eliminated
      growth defects. The dinB intragenic mutations examined were either base pair
      substitutions or those that we inferred to be loss of function (i.e., deletions
      and insertions). Further analyses of selected novel dinB alleles, generated by
      single-base-pair substitutions in the dnaE915 strain, indicated that these no
      longer effect loss of survival upon overproduction in dnaE(+) strains. These
      mutations are mapped to specific areas of DinB; this permits us to gain insights
      into the mechanisms underlying the DinB-mediated overproduction loss-of-survival
      phenotype. 

PMID- 24914187
TI  - Fifty years after the replicon hypothesis: cell-specific master regulators as new
      players in chromosome replication control.
AB  - Numerous free-living bacteria undergo complex differentiation in response to
      unfavorable environmental conditions or as part of their natural cell cycle.
      Developmental programs require the de novo expression of several sets of genes
      responsible for morphological, physiological, and metabolic changes, such as
      spore/endospore formation, the generation of flagella, and the synthesis of
      antibiotics. Notably, the frequency of chromosomal replication initiation events
      must also be adjusted with respect to the developmental stage in order to ensure
      that each nascent cell receives a single copy of the chromosomal DNA. In this
      review, we focus on the master transcriptional factors, Spo0A, CtrA, and AdpA,
      which coordinate developmental program and which were recently demonstrated to
      control chromosome replication. We summarize the current state of knowledge on
      the role of these developmental regulators in synchronizing the replication with
      cell differentiation in Bacillus subtilis, Caulobacter crescentus, and
      Streptomyces coelicolor, respectively. 

PMID- 24914190
TI  - Epigenetic upregulation of large-conductance Ca2+-activated K+ channel expression
      in uterine vascular adaptation to pregnancy.
AB  - Our previous study demonstrated that pregnancy increased large-conductance Ca(2+)
      activated potassium channel beta1 subunit (BKbeta1) expression and large
      conductance Ca(2+)-activated potassium channel activity in uterine arteries,
      which were abrogated by chronic hypoxia. The present study tested the hypothesis
      that promoter methylation/demethylation is a key mechanism in epigenetic
      reprogramming of BKbeta1 expression patterns in uterine arteries. Ovine BKbeta1
      promoter of 2315 bp spanning from -2211 to +104 of the transcription start site
      was cloned, and an Sp1-380 binding site that contains CpG dinucleotide in its
      core binding sequences was identified. Site-directed deletion of the Sp1 site
      significantly decreased the BKbeta1 promoter activity. Estrogen receptor-alpha
      bound to the Sp1 site through tethering to Sp1 and upregulated the expression of
      BKbeta1. The Sp1 binding site at BKbeta1 promoter was highly methylated in
      uterine arteries of nonpregnant sheep, and methylation inhibited transcription
      factor binding and BKbeta1 promoter activity. Pregnancy caused a significant
      decrease in CpG methylation at the Sp1 binding site and increased Sp1 binding to
      the BKbeta1 promoter and BKbeta1 mRNA abundance. Chronic hypoxia during gestation
      abrogated this pregnancy-induced demethylation and upregulation of BKbeta1
      expression. The results provide evidence of a novel mechanism of promoter
      demethylation in pregnancy-induced reprogramming of large-conductance Ca(2+)
      activated potassium channel expression and function in uterine arteries and
      suggest new insights of epigenetic mechanisms linking gestational hypoxia to
      aberrant uteroplacental circulation and increased risk of preeclampsia. 

PMID- 24914189
TI  - Healthy lifestyle factors and risk of cardiovascular events and mortality in
      treatment-resistant hypertension: the Reasons for Geographic and Racial
      Differences in Stroke study.
AB  - Few data exist on whether healthy lifestyle factors are associated with better
      prognosis among individuals with apparent treatment-resistant hypertension, a
      high-risk phenotype of hypertension. The purpose of this study was to assess the
      association of healthy lifestyle factors with cardiovascular events, all-cause
      mortality, and cardiovascular mortality among individuals with apparent treatment
      resistant hypertension. We studied participants (n=2043) from the population
      based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study
      with apparent treatment-resistant hypertension (blood pressure >=140/90 mm Hg
      despite the use of 3 antihypertensive medication classes or the use of >=4
      classes of antihypertensive medication regardless of blood pressure control). Six
      healthy lifestyle factors adapted from guidelines for the management of
      hypertension (normal waist circumference, physical activity >=4 times/week,
      nonsmoking, moderate alcohol consumption, high Dietary Approaches to Stop
      Hypertension diet score, and low sodium-to-potassium intake ratio) were examined.
      A greater number of healthy lifestyle factors were associated with lower risk for
      cardiovascular events (n=360) during a mean follow-up of 4.5 years. Multivariable
      adjusted hazard ratios [HR (95% confidence interval)] for cardiovascular events
      comparing individuals with 2, 3, and 4 to 6 versus 0 to 1 healthy lifestyle
      factors were 0.91 (0.68-1.21), 0.80 (0.57-1.14), and 0.63 (0.41-0.95),
      respectively (P-trend=0.020). Physical activity and nonsmoking were individual
      healthy lifestyle factors significantly associated with lower risk for
      cardiovascular events. Similar associations were observed between healthy
      lifestyle factors and risk for all-cause and cardiovascular mortality. In
      conclusion, healthy lifestyle factors, particularly physical activity and
      nonsmoking, are associated with a lower risk for cardiovascular events and
      mortality among individuals with apparent treatment-resistant hypertension. 

PMID- 24914191
TI  - Serum 25-hydroxyvitamin D and orthostatic hypotension in old people: the Pro.V.A.
      study.
AB  - Interest in the association between serum 25-hydroxyvitamin D (25OHD) and blood
      pressure has increased because recent research showed a close relationship
      between them, but there is still little information on the possible association
      between 25OHD and orthostatic hypotension. The aim of this study was to explore
      the relationship of 25OHD levels with any presence of orthostatic hypotension in
      a large group of older people. This study was part of the Progetto Veneto Anziani
      (Pro.V.A.), an Italian population-based cohort study involving people aged >65
      years. In this cross-sectional work, we considered 2640 (1081 men and 1559 women)
      with a mean age of 73.8+/-6.8 years. Orthostatic hypotension was defined as a
      drop of <=20 mm Hg in systolic or <=10 mm Hg in diastolic blood pressure <3
      minutes of orthostatism. Orthostatic hypotension was identified in 32.2% of the
      sample. The prevalence of orthostatic hypotension was higher in individuals with
      25OHD levels <50 nmol/L, but this trend was not significant (P=0.13). Individuals
      who had orthostatic hypotension had significantly lower 25OHD levels than those
      who did not (75.0+/-51.4 versus 82.6+/-54.0 nmol/L; P<0.0001). On logistic
      regression analysis, the greater likelihood of individuals with lower 25OHD
      levels having orthostatic hypotension was no longer statistically significant
      after adjusting for potential confounders (odds ratio, 1.08; 95% confidence
      interval, 0.77-1.51; P=0.67 for people with 25OHD levels <=25 nmol/L; odds ratio,
      1.01; 95% confidence interval, 0.78-1.32; P=0.92 for those with 25OHD levels
      between 25 and 50 nmol/L). In conclusion, vitamin D is not significantly
      associated with any orthostatic hypotension in older people. 

PMID- 24914192
TI  - Prostaglandin I2 and prostaglandin E2 modulate human intrarenal artery
      contractility through prostaglandin E2-EP4, prostacyclin-IP, and thromboxane A2
      TP receptors.
AB  - Cyclooxygenase inhibitors decrease renal blood flow in settings with decreased
      effective circulating volume. The present study examined the hypothesis that
      prostaglandins, prostaglandin E2 (PGE2) and prostacyclin (PGI2), induce
      relaxation of human intrarenal arteries through PGE2-EP and PGI2-IP receptors.
      Intrarenal arteries were microdissected from human nephrectomy samples (n=53,
      median diameter ~362 MUm, 88% viable, 76% relaxed in response to acetylcholine).
      Rings were suspended in myographs to record force development. In vessels with
      K(+)-induced tension (EC70: -log [mol/L]=1.36+/-0.03), PGE2 and PGI2 induced
      concentration-dependent relaxation (-log EC50: PGE2=7.1+/-0.3 and PGI2=7.7). The
      response to PGE2 displayed endothelium dependence and desensitization. Relaxation
      by PGE2 was mimicked by an EP4 receptor agonist (CAY10598, EC50=6.7+/-0.2). The
      relaxation after PGI2 was abolished by an IP receptor antagonist (BR5064, 10(-8)
      mol/L). Pretreatment of quiescent arteries with PGE2 for 5 minutes (10(-6) mol/L)
      led to a significant right shift of the concentration-response to norepinephrine
      (EC50 from 6.6+/-0.1-5.9+/-0.1). In intrarenal arteries with K(+)-induced tone,
      PGE2 and PGI2 at 10(-5) mol/L elicited increased tension. This was abolished by
      thromboxane receptor (TP) antagonist (S18886, 10(-6) mol/L). A TP agonist
      (U46619, n=6) evoked tension (EC50=8.1+/-0.2) that was inhibited by S18886.
      Polymerase chain reaction and immunoblotting showed EP4, IP, and TP receptors in
      intrarenal arteries. In conclusion, PGE2 and PGI2 may protect renal perfusion by
      activating cognate IP and EP4 receptors associated with smooth muscle cells and
      endothelium in human intrarenal arteries and contribute to increased renal
      vascular resistance at high pathological concentrations mediated by noncognate TP
      receptor. 

PMID- 24914194
TI  - Interference with peroxisome proliferator-activated receptor-gamma in vascular
      smooth muscle causes baroreflex impairment and autonomic dysfunction.
AB  - S-P467L mice expressing dominant negative peroxisome proliferator-activated
      receptor-gamma selectively in vascular smooth muscle exhibit impaired
      vasodilation, augmented vasoconstriction, hypertension, and tachycardia. We
      hypothesized that tachycardia in S-P467L mice is a result of baroreflex
      dysfunction. S-P467L mice displayed increased sympathetic traffic to the heart
      and decreased baroreflex gain and effectiveness. Carotid arteries exhibited
      inward remodeling but no changes in distensibility or stress/strain. Aortic
      depressor nerve activity in response to increased arterial pressure was blunted
      in S-P467L mice. However, the arterial pressure and heart rate responses to
      aortic depressor nerve stimulation were unaltered in S-P467L mice, suggesting
      that the central and efferent limbs of the baroreflex arc remain intact. There
      was no transgene expression in nodose ganglion and no change in expression of the
      acid-sensing ion channel-2 or -3 in nodose ganglion. There was a trend toward
      decreased expression of transient receptor potential vanilloid-1 receptor mRNA in
      nodose ganglion, but no difference in the immunochemical staining of transient
      receptor potential vanilloid-1 receptor in the termination area of the left
      aortic depressor nerve in S-P467L mice. Although there was no difference in the
      maximal calcium response to capsaicin in cultured nodose neurons from S-P467L
      mice, there was decreased desensitization of transient receptor potential
      vanilloid-1 receptor channels. In conclusion, S-P467L mice exhibit baroreflex
      dysfunction because of a defect in the afferent limb of the baroreflex arc caused
      by impaired vascular function, altered vascular structure, or compromised
      neurovascular coupling. These findings implicate vascular smooth muscle
      peroxisome proliferator activated receptor-gamma as a critical determinant of
      neurovascular signaling. 

PMID- 24914193
TI  - Downregulation of microvascular endothelial type B endothelin receptor is a
      central vascular mechanism in hypertensive pregnancy.
AB  - Preeclampsia is a pregnancy-related disorder characterized by hypertension with
      an unclear mechanism. Studies have shown endothelial dysfunction and increased
      endothelin-1 (ET-1) levels in hypertensive pregnancy (HTN-Preg). ET-1 activates
      endothelin receptor type-A in vascular smooth muscle to induce vasoconstriction,
      but the role of vasodilator endothelial endothelin receptor type-B (ETBR) in the
      changes in blood pressure (BP) and vascular function in HTN-Preg is unclear. To
      test whether downregulation of endothelial ETBR expression/activity plays a role
      in HTN-Preg, BP was measured in normal pregnancy (Norm-Preg) rats and rat model
      of HTN-Preg produced by reduction of uteroplacental perfusion pressure (RUPP),
      and mesenteric microvessels were isolated for measuring diameter, [Ca(2+)]i, and
      endothelin receptor type-A and ETBR levels. BP, ET-1- and potassium chloride
      induced vasoconstriction, and [Ca(2+)]i were greater in RUPP than in Norm-Preg
      rats. Endothelium removal or microvessel treatment with ETBR antagonist BQ-788
      enhanced ET-1 vasoconstriction and [Ca(2+)]i in Norm-Preg, but not RUPP,
      suggesting reduced vasodilator ETBR in HTN-Preg. The ET-1+endothelin receptor
      type-A antagonist BQ-123 and the ETBR agonists sarafotoxin 6c and IRL-1620 caused
      less vasorelaxation and nitrate/nitrite production in RUPP than in Norm-Preg. The
      nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester reduced
      sarafotoxin 6c- and IRL-1620-induced relaxation in Norm-Preg but not in RUPP,
      supporting that ETBR-mediated nitric oxide pathway is compromised in RUPP.
      Reverse transcription polymerase chain reaction, Western blots, and
      immunohistochemistry revealed reduced endothelial ETBR expression in RUPP.
      Infusion of BQ-788 increased BP in Norm-Preg, and infusion of IRL-1620 reduced BP
      and ET-1 vasoconstriction and [Ca(2+)]i and enhanced ETBR-mediated vasorelaxation
      in RUPP. Thus, downregulation of microvascular vasodilator ETBR is a central
      mechanism in HTN-Preg, and increasing ETBR activity could be a target in managing
      preeclampsia. 

PMID- 24914195
TI  - Dietary salt intake exaggerates sympathetic reflexes and increases blood pressure
      variability in normotensive rats.
AB  - Previous studies have reported that chronic increases in dietary salt intake
      enhance sympathetic nerve activity and arterial blood pressure (ABP) responses
      evoked from brain stem nuclei of normotensive, salt-resistant rats. The purpose
      of the present study was to determine whether this sensitization results in
      exaggerated sympathetic nerve activity and ABP responses during activation of
      various cardiovascular reflexes and also increases ABP variability. Male Sprague
      Dawley rats were fed 0.1% NaCl chow (low), 0.5% NaCl chow (medium), 4.0% NaCl
      chow (high) for 14 to 17 days. Then, the animals were prepared for recordings of
      lumbar, renal, and splanchnic sympathetic nerve activity and ABP. The level of
      dietary salt intake directly correlated with the magnitude of sympathetic nerve
      activity and ABP responses to electrical stimulation of sciatic afferents or
      intracerebroventricular infusion of 0.6 mol/L or 1.0 mol/L NaCl. Similarly, there
      was a direct correlation between the level of dietary salt intake and the
      sympathoinhibitory responses produced by acute volume expansion and stimulation
      of the aortic depressor nerve or cervical vagal afferents. In contrast, dietary
      salt intake did not affect the sympathetic and ABP responses to chemoreflex
      activation produced by hypoxia or hypercapnia. Chronic lesion of the
      anteroventral third ventricle region eliminated the ability of dietary salt
      intake to modulate these cardiovascular reflexes. Finally, rats chronically
      instrumented with telemetry units indicate that increased dietary salt intake
      elevated blood pressure variability but not mean ABP. These findings indicate
      that dietary salt intake works through the forebrain hypothalamus to modulate
      various centrally mediated cardiovascular reflexes and increase blood pressure
      variability. 

PMID- 24914196
TI  - The ATP-sensitive potassium channel subunit, Kir6.1, in vascular smooth muscle
      plays a major role in blood pressure control.
AB  - ATP-sensitive potassium channels (KATP) regulate a range of biological activities
      by coupling membrane excitability to the cellular metabolic state. In particular,
      it has been proposed that KATP channels and specifically, the channel subunits
      Kir6.1 and SUR2B, play an important role in the regulation of vascular tone.
      However, recent experiments have suggested that KATP channels outside the
      vascular smooth muscle compartment are the key determinant of the observed
      behavior. Thus, we address the importance of the vascular smooth muscle KATP
      channel, using a novel murine model in which it is possible to conditionally
      delete the Kir6.1 subunit. Using a combination of molecular,
      electrophysiological, in vitro, and in vivo techniques, we confirmed the absence
      of Kir6.1 and KATP currents and responses specifically in smooth muscle. Mice
      with conditional deletion of Kir6.1 showed no obvious arrhythmic phenotype even
      after provocation with ergonovine. However, these mice were hypertensive and
      vascular smooth muscle cells failed to respond to vasodilators in a normal
      fashion. Thus, Kir6.1 underlies the vascular smooth muscle KATP channel and has a
      key role in vascular reactivity and blood pressure control. 

PMID- 24914197
TI  - Down but not out: an emerging role for the B-type endothelin receptor in
      placental ischemia-induced hypertension.

PMID- 24914199
TI  - Beyond subjective cognitive failures in patients with hypertension?

PMID- 24914198
TI  - Association of longitudinal changes in left ventricular structure and function
      with myocardial fibrosis: the Multi-Ethnic Study of Atherosclerosis study.
AB  - The association of longitudinal changes in left ventricular (LV) structure and
      function with myocardial fibrosis is unclear. We relate temporal changes in body
      size-indexed LV mass (LVMi) and end-diastolic volume indexed to body surface
      area, LV mass-to-volume ratio, and LV ejection fraction (LVEF) from cine cardiac
      magnetic resonance for 10 years, with replacement scar assessed from late
      gadolinium enhancement, and lower postcontrast T1 times reflecting greater
      diffuse myocardial fibrosis measured at the end of the follow-up period. All
      participants (n=1813) who underwent cardiac magnetic resonance twice as part of
      the Multi-Ethnic Study of Atherosclerosis 10 years apart were included.
      Multivariable logistic and linear regression models adjusted for cardiovascular
      risk factors measured the association of 10-year changes in LV structure and
      function, with fibrosis measured at follow-up. The presence of LV scar at year 10
      was cross-sectionally associated with higher LVMi (~10 g/m(2)), higher mass-to
      volume ratio (0.1-0.2 g/mL), but lower LVEF (~4%) and longitudinally with 3%
      decrease in LVEF and 0.7% greater end-diastolic volume indexed to body surface
      area in men for 10 years. Lower postcontrast T1 times at year 10 were associated
      cross-sectionally with lower LVMi (r=0.33), end-diastolic volume indexed to body
      surface area (r=0.25), and LVEF (in men only: r=0.14) and longitudinally with a
      decrease in LVMi (r=0.20) and reduction in LVEF (in men only: r=0.15). Sustained
      hypertension for 10 years was associated with increased LVMi and higher diffuse
      and replacement fibrosis at follow-up. During a 10-year period, increased
      concentric hypertrophy in women and LV dilatation in men were associated with
      replacement fibrosis, whereas decreasing LVMi was associated with diffuse
      fibrosis. Hypertension-induced remodeling was related to enhanced replacement and
      diffuse fibrosis, as well as hypertrophy. 

PMID- 24914201
TI  - Verdict in the smooth muscle KATP channel case: guilty of blood pressure control
      but innocent of sudden death phenotype.

PMID- 24914200
TI  - Female spontaneously hypertensive rats have a compensatory increase in renal
      regulatory T cells in response to elevations in blood pressure.
AB  - Female spontaneously hypertensive rats (SHR) have more regulatory T cells (Tregs)
      in their kidneys than males. The goal of this study was to determine the impact
      of blood pressure (BP) on the renal immune profile. We hypothesize that increases
      in BP promote a proinflammatory renal T cell and cytokine profile in SHR,
      although females will have greater hormone-dependent increases in Tregs and males
      will have greater increases in Th17 cells. Renal T cell and cytokine profiles
      were assessed in male and female Wistar-Kyoto rats and male and female SHR
      treated with vehicle or hydrochlorothiazide and reserpine (HCTZ) from 6 to 12 (6
      HCTZ) or 11 to 13 weeks of age (2-HCTZ). Regardless of sex, SHR had a more
      proinflammatory renal immune profile than Wistar-Kyoto rats. 6-HCTZ attenuated
      age-related increases in BP and 2-HCTZ reversed hypertension compared with
      vehicle-treated SHR. Neither 6-HCTZ nor 2-HCTZ altered CD3(+), CD4(+), or CD8(+)
      T cells in either sex. Both treatments decreased Tregs only in female SHR
      abolishing sex differences in Tregs. 6-HCTZ has no impact on Th17 cells in either
      sex and 2-HCTZ had a minimal impact on renal Th17 cells. To further assess
      mechanisms mediating sex differences in the renal immune profile, male and female
      SHR were gonadectomized to determine the impact of sex hormones. Gonadectomy
      increased proinflammatory markers in both sexes, suggesting that both male and
      female sex hormones are anti-inflammatory. In conclusion, BP contributes to sex
      differences in the renal T-cell profile of SHR; female SHR increase renal Tregs
      in response to increases in BP. 

PMID- 24914202
TI  - Resistant hypertension and healthy lifestyle: impact on prognosis.

PMID- 24914203
TI  - Plasma levels of nitric oxide metabolites are markedly reduced in normotensive
      men with electrocardiographically determined left ventricular hypertrophy.
AB  - Recent studies have revealed that electrocardiographically determined left
      ventricular hypertrophy (ECG-LVH) is a risk factor for cardiovascular death not
      only in hypertensive patients but also in normotensive subjects. However, the
      underlying mechanisms remain to be elucidated. In this study, we tested our
      hypothesis that normotensive subjects with ECG-LVH have reduced nitric oxide
      production. A total of 840 Japanese male workers were enrolled, and 579 eligible
      subjects were studied. ECG-LVH was assessed according to the Sokolow-Lyon voltage
      criteria and the Cornell voltage-duration product. The median level of plasma NOx
      (nitrite plus nitrate), a marker of systemic nitric oxide production, was
      markedly lower in the normotensive subjects with ECG-LVH (n=73) than in those
      without (n=506), and the clinical characteristics were significantly different
      between the 2 groups (each P<0.05). Importantly, a one-to-one propensity score
      matching analysis showed similar markedly lower median plasma NOx level in the
      normotensive subjects with ECG-LVH compared with that observed in the matched
      normotensive subjects without ECG-LVH (P<0.05). Furthermore, the tertiles of the
      plasma NOx levels were inversely correlated with the prevalence and severity of
      ECG-LVH (both P<0.05). The lower plasma NOx levels were associated with
      significantly higher plasma 8-isoprostane levels, a marker of systemic lipid
      peroxidation (P<0.05). These results provide the first evidence that normotensive
      subjects with ECG-LVH exhibit defective nitric oxide production, along with
      increased oxidative stress. Our findings may thus explain, at least in part, a
      potential mechanism underlying the increased risk of cardiovascular death in
      normotensive individuals with ECG-LVH. 

PMID- 24914204
TI  - Subjective cognitive failures in patients with hypertension are related to
      cognitive performance and cerebral microbleeds.
AB  - Previous studies on the relationship between subjective cognitive failures (SCF)
      and objective cognitive function have shown inconsistent results. In addition,
      research on the association between SCF and imaging markers of cerebral small
      vessel disease is limited. We investigated whether SCF in patients with essential
      hypertension, who are at high risk of cerebral small vessel disease, are
      associated with objective cognitive function and magnetic resonance imaging
      manifestations of cerebral small vessel disease. We included 109 patients with
      hypertension who underwent extensive neuropsychological assessment, including
      questionnaires measuring SCF and symptoms of anxiety and depression. Brain
      magnetic resonance imaging was performed to rate the presence of lacunes,
      cerebral microbleeds, and perivascular spaces, as well as white matter
      hyperintensities volume. Results showed significant associations between SCF and
      objectively measured overall cognition (B=-0.02; 95% confidence interval=-0.03 to
      -0.005), memory (B=0.02; 95% confidence interval=-0.03 to -0.004), and
      information processing speed (B=-0.02; 95% confidence interval=-0.03 to -0.001)
      after adjustment for patient characteristics and vascular risk factors. In
      addition, SCF were associated with the presence of cerebral microbleeds (odds
      ratio=1.12; 95% confidence interval=1.02-1.23) after adjustment for patient
      characteristics and vascular risk factors but not with other imaging markers of
      cerebral small vessel disease. Our study demonstrates that attention for SCF in
      patients with hypertension is needed because these may point to lower objective
      cognitive function, which might be as a result of the presence of cerebral
      microbleeds. Accordingly, this study emphasizes that neuropsychological
      assessment and brain imaging need to be considered when patients with
      hypertension report SCF. 

PMID- 24914205
TI  - Synergistic signaling of tumor cell invasiveness by hepatocyte growth factor and
      hypoxia.
AB  - Hepatocyte growth factor (HGF) signaling promotes tumor invasiveness in renal
      cell carcinoma (RCC) and other cancers. In clear cell RCC, VHL loss generates
      pseudohypoxia that exacerbates HGF-driven invasion through beta-catenin
      deregulation. Hypoxia also enhances HGF-driven invasiveness by papillary RCC
      cells, but in the absence of VHL, loss signaling integration involves three
      parallel routes: 1) hypoxia-induced reactive oxygen species production and
      decreased DUSP2 expression, leading to enhanced mitogen-activated protein kinase
      (MAPK) cascade activation; 2) reactive oxygen species-induced diacylglycerol
      production by phospholipase Cgamma, leading to protein kinase C activation and
      increased protein phosphatase- 2A activity, thereby suppressing HGF-induced Akt
      activation; and 3) a profound shift from HGF-enhanced, proliferation- oriented
      metabolism to autophagy-dependent invasion and suppression of proliferation. This
      tripartite signaling integration was not unique to RCC or HGF; in RCC cells,
      invasive synergy induced by the combination of hypoxia and epidermal growth
      factor occurred through the same mechanism, and in estrogen receptor-positive
      breast cancer cells, this mechanism was suppressed in the absence of estrogen.
      These results define the molecular basis of growth factor and hypoxia invasive
      synergy in VHL-competent papillary RCC cells, illustrate the plasticity of
      invasive and proliferative tumor cell states, and provide signaling profiles by
      which they may be predicted.

PMID- 24914206
TI  - Differential regulation of cyclin D1 expression by protein kinase C alpha and
      epsilon signaling in intestinal epithelial cells.
AB  - Cellular accumulation of cyclin D1, a key regulator of cell proliferation and
      tumorigenesis, is subject to tight control. Our previous studies have identified
      PKCalpha as a negative regulator of cyclin D1 in the intestinal epithelium.
      However, treatment of non-transformed IEC-18 ileal crypt cells with PKC agonists
      has a biphasic effect on cyclin D1 expression. Initial PKCalpha-mediated down
      regulation is followed by recovery and subsequent accumulation of the cyclin to
      levels markedly higher than those seen in untreated cells. Using protein
      overexpression strategies, siRNA, and pharmacological inhibitors, we now
      demonstrate that the recovery and hyperinduction of cyclin D1 reflect the
      combined effects of (a) loss of negative signals from PKCalpha due to agonist
      induced PKCalpha down-regulation and (b) positive effects of PKCepsilon.
      PKCepsilon-mediated up-regulation of cyclin D1 requires sustained ERK stimulation
      and transcriptional activation of the proximal cyclin D1 (CCDN1) promoter,
      without apparent involvement of changes in protein stability or translation.
      PKCepsilon also up-regulates cyclin D1 expression in colon cancer cells, through
      mechanisms that parallel those in IEC-18 cells. Although induction of cyclin D1
      by PKCepsilon is dependent on non-canonical NF-kappaB activation, the NF-kappaB
      site in the proximal promoter is not required. Instead, cyclin D1 promoter
      activity is regulated by a novel interaction between NF-kappaB and factors that
      associate with the cyclic AMP-response element adjacent to the NF-kappaB site.
      The differential effects of PKCalpha and PKCepsilon on cyclin D1 accumulation are
      likely to contribute to the opposing tumor-suppressive and tumor-promoting
      activities of these PKC family members in the intestinal epithelium. 

PMID- 24914208
TI  - Cross-linking evidence for multiple interactions of the PsbP and PsbQ proteins in
      a higher plant photosystem II supercomplex.
AB  - The extrinsic subunits of membrane-bound photosystem II (PSII) maintain an
      essential role in optimizing the water-splitting reaction of the oxygen-evolving
      complex (OEC), even though they have undergone drastic change during the
      evolution of oxyphototrophs from symbiotic cyanobacteria to chloroplasts. Two
      specific extrinsic proteins, PsbP and PsbQ, bind to the lumenal surface of PSII
      in green plants and maintain OEC conformation and stabilize overall enzymatic
      function; however, their precise location has not been fully resolved. In this
      study, PSII-enriched membranes, isolated from spinach, were subjected to chemical
      cross-linking combined with release-reconstitution experiments. We observed
      direct interactions between PsbP and PsbE, as well as with PsbR. Intriguingly,
      PsbP and PsbQ were further linked to the CP26 and CP43 light-harvesting proteins.
      In addition, two cross-linked sites, between PsbP and PsbR, and that of PsbP and
      CP26, were identified by tandem mass spectrometry. These data were used to
      estimate the binding topology and location of PsbP, and the putative positioning
      of PsbQ and PsbR on the lumenal surface of the PSII. Our model gives new insights
      into the organization of PSII extrinsic subunits in higher plants and their
      function in stabilizing the OEC of the PSII supercomplex. 

PMID- 24914209
TI  - Identification of Novel Peptidyl Serine alpha-Galactosyltransferase Gene Family
      in Plants.
AB  - In plants, serine residues in extensin, a cell wall protein, are glycosylated
      with O-linked galactose. However, the enzyme that is involved in the
      galactosylation of serine had not yet been identified. To identify the peptidyl
      serine O-alpha-galactosyltransferase (SGT), we chose Chlamydomonas reinhardtii as
      a model. We established an assay system for SGT activity using C. reinhardtii and
      Arabidopsis thaliana cell extracts. SGT protein was partially purified from cell
      extracts of C. reinhardtii and analyzed by tandem mass spectrometry to determine
      its amino acid sequence. The sequence matched the open reading frame XP_001696927
      in the C. reinhardtii proteome database, and a corresponding DNA fragment
      encoding 748 amino acids (BAL63043) was cloned from a C. reinhardtii cDNA
      library. The 748-amino acid protein (CrSGT1) was produced using a yeast
      expression system, and the SGT activity was examined. Hydroxylation of proline
      residues adjacent to a serine in acceptor peptides was required for SGT activity.
      Genes for proteins containing conserved domains were found in various plant
      genomes, including A. thaliana and Nicotiana tabacum. The AtSGT1 and NtSGT1
      proteins also showed SGT activity when expressed in yeast. In addition, knock-out
      lines of AtSGT1 and knockdown lines of NtSGT1 showed no or reduced SGT activity.
      The SGT1 sequence, which contains a conserved DXD motif and a C-terminal membrane
      spanning region, is the first example of a glycosyltransferase with type I
      membrane protein topology, and it showed no homology with known
      glycosyltransferases, indicating that SGT1 belongs to a novel glycosyltransferase
      gene family existing only in the plant kingdom.

PMID- 24914207
TI  - Cytoskeletal reorganization evoked by Rho-associated kinase- and protein kinase C
      catalyzed phosphorylation of cofilin and heat shock protein 27, respectively,
      contributes to myogenic constriction of rat cerebral arteries.
AB  - Our understanding of the molecular events contributing to myogenic control of
      diameter in cerebral resistance arteries in response to changes in intravascular
      pressure, a fundamental mechanism regulating blood flow to the brain, is
      incomplete. Myosin light chain kinase and phosphatase activities are known to be
      increased and decreased, respectively, to augment phosphorylation of the 20-kDa
      regulatory light chain subunits (LC20) of myosin II, which permits cross-bridge
      cycling and force development. Here, we assessed the contribution of dynamic
      reorganization of the actin cytoskeleton and thin filament regulation to the
      myogenic response and serotonin-evoked constriction of pressurized rat middle
      cerebral arteries. Arterial diameter and the levels of phosphorylated LC(20),
      calponin, caldesmon, cofilin, and HSP27, as well as G-actin content, were
      determined. A decline in G-actin content was observed following pressurization
      from 10 mm Hg to between 40 and 120 mm Hg and in three conditions in which
      myogenic or agonist-evoked constriction occurred in the absence of a detectable
      change in LC20 phosphorylation. No changes in thin filament protein
      phosphorylation were evident. Pressurization reduced G-actin content and elevated
      the levels of cofilin and HSP27 phosphorylation. Inhibitors of Rho-associated
      kinase and PKC prevented the decline in G-actin; reduced cofilin and HSP27
      phosphoprotein content, respectively; and blocked the myogenic response.
      Furthermore, phosphorylation modulators of HSP27 and cofilin induced significant
      changes in arterial diameter and G-actin content of myogenically active arteries.
      Taken together, our findings suggest that dynamic reorganization of the
      cytoskeleton involving increased actin polymerization in response to Rho
      associated kinase and PKC signaling contributes significantly to force generation
      in myogenic constriction of cerebral resistance arteries.

PMID- 24914210
TI  - Mechanism of dephosphorylation of glucosyl-3-phosphoglycerate by a histidine
      phosphatase.
AB  - Mycobacterium tuberculosis (Mtb) synthesizes polymethylated polysaccharides that
      form complexes with long chain fatty acids. These complexes, referred to as
      methylglucose lipopolysaccharides (MGLPs), regulate fatty acid biosynthesis in
      vivo, including biosynthesis of mycolic acids that are essential for building the
      cell wall. Glucosyl-3-phosphoglycerate phosphatase (GpgP, EC 5.4.2.1), encoded by
      Rv2419c gene, catalyzes the second step of the pathway for the biosynthesis of
      MGLPs. The molecular basis for this dephosphorylation is currently not
      understood. Here, we describe the crystal structures of apo-, vanadate-bound, and
      phosphate-bound MtbGpgP, depicting unliganded, reaction intermediate mimic, and
      product-bound views of MtbGpgP, respectively. The enzyme consists of a single
      domain made up of a central beta-sheet flanked by alpha-helices on either side.
      The active site is located in a positively charged cleft situated above the
      central beta-sheet. Unambiguous electron density for vanadate covalently bound to
      His(11), mimicking the phosphohistidine intermediate, was observed. The role of
      residues interacting with the ligands in catalysis was probed by site-directed
      mutagenesis. Arg(10), His(11), Asn(17), Gln(23), Arg(60), Glu(84), His(159), and
      Leu(209) are important for enzymatic activity. Comparison of the structures of
      MtbGpgP revealed conformational changes in a key loop region connecting beta1
      with alpha1. This loop regulates access to the active site. MtbGpgP functions as
      dimer. L209E mutation resulted in monomeric GpgP, rendering the enzyme incapable
      of dephosphorylation. The structures of GpgP reported here are the first crystal
      structures for histidine-phosphatase-type GpgPs. These structures shed light on a
      key step in biosynthesis of MGLPs that could be targeted for development of anti
      tuberculosis therapeutics. 

PMID- 24914211
TI  - Self-assembly of MinE on the membrane underlies formation of the MinE ring to
      sustain function of the Escherichia coli Min system.
AB  - The pole-to-pole oscillation of the Min proteins in Escherichia coli results in
      the inhibition of aberrant polar division, thus facilitating placement of the
      division septum at the midcell. MinE of the Min system forms a ring-like
      structure that plays a critical role in triggering the oscillation cycle.
      However, the mechanism underlying the formation of the MinE ring remains unclear.
      This study demonstrates that MinE self-assembles into fibrillar structures on the
      supported lipid bilayer. The MinD-interacting domain of MinE shows amyloidogenic
      properties, providing a possible mechanism for self-assembly of MinE. Supporting
      the idea, mutations in residues Ile-24 and Ile-25 of the MinD-interacting domain
      affect fibril formation, membrane binding ability of MinE and MinD, and
      subcellular localization of three Min proteins. Additional mutations in residues
      Ile-72 and Ile-74 suggest a role of the C-terminal domain of MinE in regulating
      the folding propensity of the MinD-interacting domain for different molecular
      interactions. The study suggests a self-assembly mechanism that may underlie the
      ring-like structure formed by MinE-GFP observed in vivo. 

PMID- 24914212
TI  - An interactive network of elastase, secretases, and PAR-2 protein regulates CXCR1
      receptor surface expression on neutrophils.
AB  - CXCL8 (IL-8) recruits and activates neutrophils through the G protein-coupled
      chemokine receptor CXCR1. We showed previously that elastase cleaves CXCR1 and
      thereby impairs antibacterial host defense. However, the molecular intracellular
      machinery involved in this process remained undefined. Here we demonstrate by
      using flow cytometry, confocal microscopy, subcellular fractionation, co
      immunoprecipitation, and bioluminescence resonance energy transfer that combined
      alpha- and gamma-secretase activities are functionally involved in elastase
      mediated regulation of CXCR1 surface expression on human neutrophils, whereas
      matrix metalloproteases are dispensable. We further demonstrate that PAR-2 is
      stored in mobilizable compartments in neutrophils. Bioluminescence resonance
      energy transfer and co-immunoprecipitation studies showed that secretases, PAR-2,
      and CXCR1 colocalize and physically interact in a novel protease/secretase
      chemokine receptor network. PAR-2 blocking experiments provided evidence that
      elastase increased intracellular presenilin-1 expression through PAR-2 signaling.
      When viewed in combination, these studies establish a novel functional network of
      elastase, secretases, and PAR-2 that regulate CXCR1 expression on neutrophils.
      Interfering with this network could lead to novel therapeutic approaches in
      neutrophilic diseases, such as cystic fibrosis or rheumatoid arthritis.

PMID- 24914213
TI  - Protein degradation and quality control in cells from laforin and malin knockout
      mice.
AB  - Lafora disease is a progressive myoclonus epilepsy caused by mutations in the
      EPM2A or EPM2B genes that encode a glycogen phosphatase, laforin, and an E3
      ubiquitin ligase, malin, respectively. Lafora disease is characterized by
      accumulation of insoluble, poorly branched, hyperphosphorylated glycogen in
      brain, muscle, heart, and liver. The laforinmalin complex has been proposed to
      play a role in the regulation of glycogen metabolism and protein quality control.
      We evaluated three arms of the protein degradation/ quality control process (the
      autophago-lysosomal pathway, the ubiquitin-proteasomal pathway, and the
      endoplasmic reticulum (ER) stress response) in mouse embryonic fibroblasts from
      Epm2a(-/-), Epm2b(-/-), and Epm2a(-/-) Epm2b(-/-) mice. The levels of LC3-II, a
      marker of autophagy, were decreased in all knock-out cells as compared with wild
      type even though they still showed a slight response to starvation and rapamycin.
      Furthermore, ribosomal protein S6 kinase and S6 phosphorylation were increased.
      Under basal conditions there was no effect on the levels of ubiquitinated
      proteins in the knock-out cells, but ubiquitinated protein degradation was
      decreased during starvation or stress. Lack of malin (Epm2b(-/-) and Epm2a(-/-)
      Epm2b(-/-) cells) but not laforin (Epm2a(-/-) cells) decreased LAMP1, a lysosomal
      marker. CHOP expression was similar in wild type and knock-out cells under basal
      conditions or with ER stress-inducing agents. In conclusion, both laforin and
      malin knock-out cells display mTOR-dependent autophagy defects and reduced
      proteasomal activity but no defects in the ER stress response. We speculate that
      these defects may be secondary to glycogen overaccumulation. This study also
      suggests a malin function independent of laforin, possibly in lysosomal
      biogenesis and/or lysosomal glycogen disposal.

PMID- 24914214
TI  - Microbiota-driven immune cellular maturation is essential for antibody-mediated
      adaptive immunity to Staphylococcus aureus infection in the eye.
AB  - As an immune-privileged site, the eye, and particularly the outer corneal
      surface, lacks resident mature immune effector cells. Physical barriers and
      innate mediators are the best-described effectors of immunity in the cornea. When
      the barriers are breached, infection can result in rapid tissue destruction,
      leading to loss of visual acuity and frank blindness. To determine the cellular
      and molecular components needed for effective adaptive immunity on the corneal
      surface, we investigated which immune system effectors were required for
      protection against Staphylococcus aureus corneal infections in mice, which are a
      serious cause of human eye infections. Both systemically injected and topically
      applied antibodies to the conserved cell surface polysaccharide poly-N
      acetylglucosamine (PNAG) were effective at mediating reductions in corneal
      pathology and bacterial levels. Additional host factors impacting protection
      included intercellular adhesion molecule 1 (ICAM-1)-dependent polymorphonuclear
      leukocyte (PMN) recruitment, functional CD4(+) T cells, signaling via the
      interleukin-17 (IL-17) receptor, and IL-22 production. In germfree mice, there
      was no protective efficacy of antibody to PNAG due to the lack of LY6G(+)
      inflammatory cell coeffector recruitment to the cornea. Protection was manifest
      after 3 weeks of exposure to conventional mice and acquisition of a resident
      microbiota. We conclude that in the anterior eye, ICAM-1-mediated PMN recruitment
      to the infected cornea along with endogenous microbiota-matured CD4(+) T cells
      producing both IL-17 and IL-22 is required for antibody to PNAG to protect
      against S. aureus infection. 

PMID- 24914215
TI  - CcpA is important for growth and virulence of Enterococcus faecium.
AB  - The collagen adhesin Acm was the first virulence determinant reported to be
      important for the pathogenesis of Enterococcus faecium in a rat infective
      endocarditis model. We had previously reported that there was a slight growth
      delay associated with acm allelic replacement (cat) mutant strain TX6051 used in
      that study. Recently, we generated a nonpolar markerless acm deletion mutant and
      did not observe a delay in growth. We therefore performed comparative genome
      sequence analysis of wild-type strain TX82 and TX6051 and found a single
      mutation, a nonsense mutation in the ccpA gene of TX6051. After correcting this
      mutation, the growth defect of TX6051 was abolished, implicating a role for CcpA
      in the growth of E. faecium. To confirm this, we created a ccpA deletion mutant
      of TX82, which also exhibited a slight delay in growth. Furthermore, the ccpA
      deletion mutant was attenuated (P = 0.0024) in a mixed-inoculum (TX82 plus TX82
      DeltaccpA) rat endocarditis model and also in an in vitro competitive growth
      assay; a ccpA-complemented strain showed neither reduced growth nor reduced
      virulence. We also found attenuation in the endocarditis model with the new acm
      deletion mutant although not as great as that previously observed with TX6051
      carrying the ccpA mutation. Taken together, our data confirm the role of Acm in
      the pathogenesis of endocarditis. We also show that CcpA affects the growth of E.
      faecium, that an intact ccpA gene is important for full virulence, and that a
      ccpA mutation was partly responsible for the highly attenuated phenotype of
      TX6051. 

PMID- 24914216
TI  - Differential effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on
      chemokine and proinflammatory cytokine expression in human macrophage, colonic
      epithelial, and brain microvascular endothelial cell lines.
AB  - Subtilase cytotoxin (SubAB) is the prototype of a recently emerged family of AB5
      cytotoxins produced by Shiga-toxigenic Escherichia coli (STEC). Its mechanism of
      action involves highly specific A-subunit-mediated proteolytic cleavage of the
      essential endoplasmic reticulum (ER) chaperone BiP. Our previous in vivo studies
      showed that intraperitoneal injection of purified SubAB causes a major
      redistribution of leukocytes and elevated leukocyte apoptosis in mice, as well as
      profound splenic atrophy. In the current study, we investigated selected
      chemokine and proinflammatory cytokine responses to treatment with SubAB, a
      nontoxic derivative (SubAA272B), or Shiga toxin 2 (Stx2) in human macrophage
      (U937), brain microvascular endothelial (HBMEC), and colonic epithelial (HCT-8)
      cell lines, at the levels of secreted protein, cell-associated protein, and gene
      expression. Stx2 treatment upregulated expression of chemokines and cytokines at
      both the protein and mRNA levels. In contrast, SubAB induced significant
      decreases in secreted interleukin-8 (IL-8) and monocyte chemoattractant protein 1
      (MCP-1) in all three tested cell lines and a significant decrease in secreted IL
      6 in HBMECs. The downregulation of secreted chemokines or cytokines was not
      observed in SubAA272B-treated cells, indicating a requirement for BiP cleavage.
      The downregulation of secreted chemokines and cytokines by SubAB was not
      reflected at the mRNA and cell-associated protein levels, suggesting a SubAB
      induced export defect. 

PMID- 24914218
TI  - Substrate binding protein SBP2 of a putative ABC transporter as a novel vaccine
      antigen of Moraxella catarrhalis.
AB  - Moraxella catarrhalis is a common respiratory tract pathogen that causes otitis
      media in children and infections in adults with chronic obstructive pulmonary
      disease. Since the introduction of the pneumococcal conjugate vaccines
      with/without protein D of nontypeable Haemophilus influenzae, M. catarrhalis has
      become a high-priority pathogen in otitis media. For the development of
      antibacterial vaccines and therapies, substrate binding proteins of ATP-binding
      cassette transporters are important targets. In this study, we identified and
      characterized a substrate binding protein, SBP2, of M. catarrhalis. Among 30
      clinical isolates tested, the sbp2 gene sequence was highly conserved. In 2
      different analyses (whole-cell enzyme-linked immunosorbent assay and flow
      cytometry), polyclonal antibodies raised to recombinant SBP2 demonstrated that
      SBP2 expresses epitopes on the bacterial surface of the wild type but not the
      sbp2 mutant. Mice immunized with recombinant SBP2 showed significantly enhanced
      clearance of M. catarrhalis from the lung compared to that in the control group
      at both 25-MUg and 50-MUg doses (P < 0.001). We conclude that SBP2 is a novel,
      attractive candidate as a vaccine antigen against M. catarrhalis. 

PMID- 24914217
TI  - A (p)ppGpp-null mutant of Haemophilus ducreyi is partially attenuated in humans
      due to multiple conflicting phenotypes.
AB  - (p)ppGpp responds to nutrient limitation through a global change in gene
      regulation patterns to increase survival. The stringent response has been
      implicated in the virulence of several pathogenic bacterial species. Haemophilus
      ducreyi, the causative agent of chancroid, has homologs of both relA and spoT,
      which primarily synthesize and hydrolyze (p)ppGpp in Escherichia coli. We
      constructed relA and relA spoT deletion mutants to assess the contribution of
      (p)ppGpp to H. ducreyi pathogenesis. Both the relA single mutant and the relA
      spoT double mutant failed to synthesize (p)ppGpp, suggesting that relA is the
      primary synthetase of (p)ppGpp in H. ducreyi. Compared to the parent strain, the
      double mutant was partially attenuated for pustule formation in human volunteers.
      The double mutant had several phenotypes that favored attenuation, including
      increased sensitivity to oxidative stress. The increased sensitivity to oxidative
      stress could be complemented in trans. However, the double mutant also exhibited
      phenotypes that favored virulence. When grown to the mid-log phase, the double
      mutant was significantly more resistant than its parent to being taken up by
      human macrophages and exhibited increased transcription of lspB, which is
      involved in resistance to phagocytosis. Additionally, compared to the parent, the
      double mutant also exhibited prolonged survival in the stationary phase. In E.
      coli, overexpression of DksA compensates for the loss of (p)ppGpp; the H. ducreyi
      double mutant expressed higher transcript levels of dksA than the parent strain.
      These data suggest that the partial attenuation of the double mutant is likely
      the net result of multiple conflicting phenotypes. 

PMID- 24914219
TI  - Platelet endothelial cell adhesion molecule-1, a putative receptor for the
      adhesion of Streptococcus pneumoniae to the vascular endothelium of the blood
      brain barrier.
AB  - The Gram-positive bacterium Streptococcus pneumoniae is the main causative agent
      of bacterial meningitis. S. pneumoniae is thought to invade the central nervous
      system via the bloodstream by crossing the vascular endothelium of the blood
      brain barrier. The exact mechanism by which pneumococci cross endothelial cell
      barriers before meningitis develops is unknown. Here, we investigated the role of
      PECAM-1/CD31, one of the major endothelial cell adhesion molecules, in S.
      pneumoniae adhesion to vascular endothelium of the blood-brain barrier. Mice were
      intravenously infected with pneumococci and sacrificed at various time points to
      represent stages preceding meningitis. Immunofluorescent analysis of brain tissue
      of infected mice showed that pneumococci colocalized with PECAM-1. In human brain
      microvascular endothelial cells (HBMEC) incubated with S. pneumoniae, we observed
      a clear colocalization between PECAM-1 and pneumococci. Blocking of PECAM-1
      reduced the adhesion of S. pneumoniae to endothelial cells in vitro, implying
      that PECAM-1 is involved in pneumococcal adhesion to the cells. Furthermore,
      using endothelial cell protein lysates, we demonstrated that S. pneumoniae
      physically binds to PECAM-1. Moreover, both in vitro and in vivo PECAM-1
      colocalizes with the S. pneumoniae adhesion receptor pIgR. Lastly,
      immunoprecipitation experiments revealed that PECAM-1 can physically interact
      with pIgR. In summary, we show for the first time that blood-borne S. pneumoniae
      colocalizes with PECAM-1 expressed by brain microvascular endothelium and that,
      in addition, they colocalize with pIgR. We hypothesize that this interaction
      plays a role in pneumococcal binding to the blood-brain barrier vasculature prior
      to invasion into the brain. 

PMID- 24914220
TI  - Bile acids repress hypoxia-inducible factor 1 signaling and modulate the airway
      immune response.
AB  - Gastroesophageal reflux (GER) frequently occurs in patients with respiratory
      disease and is particularly prevalent in patients with cystic fibrosis. GER is a
      condition in which the duodenogastric contents of the stomach leak into the
      esophagus, in many cases resulting in aspiration into the respiratory tract. As
      such, the presence of GER-derived bile acids (BAs) has been confirmed in the
      bronchoalveolar lavage fluid and sputum of affected patients. We have recently
      shown that bile causes cystic fibrosis-associated bacterial pathogens to adopt a
      chronic lifestyle and may constitute a major host trigger underlying respiratory
      infection. The current study shows that BAs elicit a specific response in humans
      in which they repress hypoxia-inducible factor 1alpha (HIF-1alpha) protein, an
      emerging master regulator in response to infection and inflammation. HIF-1alpha
      repression was shown to occur through the 26S proteasome machinery via the prolyl
      hydroxylase domain (PHD) pathway. Further analysis of the downstream inflammatory
      response showed that HIF-1alpha repression by BAs can significantly modulate the
      immune response of airway epithelial cells, correlating with a decrease in
      interleukin-8 (IL-8) production, while IL-6 production was strongly increased.
      Importantly, the effects of BAs on cytokine production can also be more dominant
      than the bacterium-mediated effects. However, the effect of BAs on cytokine
      levels cannot be fully explained by their ability to repress HIF-1alpha, which is
      not surprising, given the complexity of the immune regulatory network. The
      suppression of HIF-1 signaling by bile acids may have a significant influence on
      the progression and outcome of respiratory disease, and the molecular mechanism
      underpinning this response warrants further investigation. 

PMID- 24914221
TI  - Superantigens subvert the neutrophil response to promote abscess formation and
      enhance Staphylococcus aureus survival in vivo.
AB  - Staphylococcus aureus is a versatile bacterial pathogen that produces T cell
      activating toxins known as superantigens (SAgs). Although excessive immune
      activation by SAgs can induce a dysregulated cytokine storm as a component of
      what is known as toxic shock syndrome (TSS), the contribution of SAgs to the
      staphylococcal infection process is not well defined. Here, we evaluated the role
      of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia
      model using humanized transgenic mice expressing SAg-responsive HLA-DR4
      molecules. Infection with S. aureus Newman induced SEA-dependent Vbeta skewing of
      T cells and enhanced bacterial survival in the liver compared with infection by
      sea knockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine
      responses resulted in increased infiltration of CD11b(+) Ly6G(+) neutrophils into
      the liver, promoting the formation of abscesses that contained large numbers of
      viable staphylococci. Hepatic abscesses occurred significantly more frequently in
      S. aureus Newman-infected livers than in livers infected with the Newman sea
      knockout strain, promoting the survival of S. aureus in vivo. This represents a
      novel mechanism during infection whereby S. aureus utilizes SAgs to form a
      specialized niche and manipulate the immune system. 

PMID- 24914222
TI  - Host response to nontuberculous mycobacterial infections of current clinical
      importance.
AB  - The nontuberculous mycobacteria are a large group of acid-fast bacteria that are
      very widely distributed in the environment. While Mycobacterium avium was once
      regarded as innocuous, its high frequency as a cause of disseminated disease in
      HIV-positive individuals illustrated its potential as a pathogen. Much more
      recently, there is growing evidence that the incidence of M. avium and related
      nontuberculous species is increasing in immunocompetent individuals. The same has
      been observed for M. abscessus infections, which are very difficult to treat;
      accordingly, this review focuses primarily on these two important pathogens. Like
      the host response to M. tuberculosis infections, the host response to these
      infections is of the TH1 type but there are some subtle and as-yet-unexplained
      differences. 

PMID- 24914223
TI  - Involvement of Enterococcus faecalis small RNAs in stress response and virulence.
AB  - Candidate small RNAs (sRNAs) have recently been identified in Enterococcus
      faecalis, a Gram-positive opportunistic pathogen, and six of these candidate
      sRNAs with unknown functions were selected for a functional study. Deletion
      mutants and complemented strains were constructed, and their virulence was
      tested. We were unable to obtain the ef0869-0870 mutant, likely due to an
      essential role, and the ef0820-0821 sRNA seemed not to be involved in virulence.
      In contrast, the mutant lacking ef0408-0409 sRNA, homologous to the RNAII
      component of the toxin-antitoxin system, appeared more virulent and more able to
      colonize mouse organs. The three other mutants showed reduced virulence. In
      addition, we checked the responses of these mutant strains to several stresses
      encountered in the gastrointestinal tract or during the infection process. In
      parallel, the activities of the sRNA promoters were measured using
      transcriptional fusion constructions. To attempt to identify the regulons of
      these candidate sRNAs, proteomics profiles of the mutant strains were compared
      with that of the wild type. This showed that the selected sRNAs controlled the
      expression of proteins involved in diverse cellular processes and the stress
      response. The combined data highlight the roles of certain candidate sRNAs in the
      adaptation of E. faecalis to environmental changes and in the complex transition
      process from a commensal to a pathogen. 

PMID- 24914226
TI  - Recommendations for management of low-back pain misleading.

PMID- 24914224
TI  - Serratia marcescens ShlA pore-forming toxin is responsible for early induction of
      autophagy in host cells and is transcriptionally regulated by RcsB.
AB  - Serratia marcescens is a Gram-negative bacterium that thrives in a wide variety
      of ambient niches and interacts with an ample range of hosts. As an opportunistic
      human pathogen, it has increased its clinical incidence in recent years, being
      responsible for life-threatening nosocomial infections. S. marcescens produces
      numerous exoproteins with toxic effects, including the ShlA pore-forming toxin,
      which has been catalogued as its most potent cytotoxin. However, the regulatory
      mechanisms that govern ShlA expression, as well as its action toward the host,
      have remained unclear. We have shown that S. marcescens elicits an autophagic
      response in host nonphagocytic cells. In this work, we determine that the
      expression of ShlA is responsible for the autophagic response that is promoted
      prior to bacterial internalization in epithelial cells. We show that a strain
      unable to express ShlA is no longer able to induce this autophagic mechanism,
      while heterologous expression of ShlA/ShlB suffices to confer on noninvasive
      Escherichia coli the capacity to trigger autophagy. We also demonstrate that
      shlBA harbors a binding motif for the RcsB regulator in its promoter region. RcsB
      dependent control of shlBA constitutes a feed-forward regulatory mechanism that
      allows interplay with flagellar-biogenesis regulation. At the top of the circuit,
      activated RcsB downregulates expression of flagella by binding to the flhDC
      promoter region, preventing FliA-activated transcription of shlBA.
      Simultaneously, RcsB interaction within the shlBA promoter represses ShlA
      expression. This circuit offers multiple access points to fine-tune ShlA
      production. These findings also strengthen the case for an RcsB role in
      orchestrating the expression of Serratia virulence factors. 

PMID- 24914227
TI  - Recommendations for management of low-back pain misleading.

PMID- 24914228
TI  - Clarification of Borod's comments about Bill 52.

PMID- 24914229
TI  - Post-tussive carotid artery dissection: could it be whooping cough?

PMID- 24914230
TI  - Unusual venous thrombosis.

PMID- 24914231
TI  - The benefit of stimulants in reducing driving risk in adult drivers with ADHD.

PMID- 24914232
TI  - Finding abbreviations in biomedical literature: three BioC-compatible modules and
      four BioC-formatted corpora.
AB  - BioC is a recently created XML format to share text data and annotations, and an
      accompanying input/output library to promote interoperability of data and tools
      for natural language processing of biomedical text. This article reports the use
      of BioC to address a common challenge in processing biomedical text information
      that of frequent entity name abbreviation. We selected three different
      abbreviation definition identification modules, and used the publicly available
      BioC code to convert these independent modules into BioC-compatible components
      that interact seamlessly with BioC-formatted data, and other BioC-compatible
      modules. In addition, we consider four manually annotated corpora of
      abbreviations in biomedical text: the Ab3P corpus of 1250 PubMed abstracts, the
      BIOADI corpus of 1201 PubMed abstracts, the old MEDSTRACT corpus of 199
      PubMed((r)) citations and the Schwartz and Hearst corpus of 1000 PubMed
      abstracts. Annotations in these corpora have been re-evaluated by four annotators
      and their consistency and quality levels have been improved. We converted them to
      BioC-format and described the representation of the annotations. These corpora
      are used to measure the three abbreviation-finding algorithms and the results are
      given. The BioC-compatible modules, when compared with their original form, have
      no difference in their efficiency, running time or any other comparable aspects.
      They can be conveniently used as a common pre-processing step for larger multi
      layered text-mining endeavors. Database URL: Code and data are available for
      download at the BioC site: http://bioc.sourceforge.net. 

PMID- 24914233
TI  - Adam Cohen: visualizing cellular voltage.

PMID- 24914234
TI  - Poly(ADP-ribose): an organizer of cellular architecture.
AB  - Distinct properties of poly(ADP-ribose)-including its structural diversity,
      nucleation potential, and low complexity, polyvalent, highly charged nature-could
      contribute to organizing cellular architectures. Emergent data indicate that
      poly(ADP-ribose) aids in the formation of nonmembranous structures, such as DNA
      repair foci, spindle poles, and RNA granules. Informatics analyses reported here
      show that RNA granule proteins enriched for low complexity regions, which aid
      self-assembly, are preferentially modified by poly(ADP-ribose), indicating how
      poly(ADP-ribose) could direct cellular organization. 

PMID- 24914235
TI  - The cell biology of asthma.
AB  - The clinical manifestations of asthma are caused by obstruction of the conducting
      airways of the lung. Two airway cell types are critical for asthma pathogenesis:
      epithelial cells and smooth muscle cells. Airway epithelial cells, which are the
      first line of defense against inhaled pathogens and particles, initiate airway
      inflammation and produce mucus, an important contributor to airway obstruction.
      The other main cause of airway obstruction is contraction of airway smooth
      muscle. Complementary experimental approaches involving cultured cells, animal
      models, and human clinical studies have provided many insights into diverse
      mechanisms that contribute to airway epithelial and smooth muscle cell pathology
      in this complex disease. 

PMID- 24914236
TI  - A selfish DNA element engages a meiosis-specific motor and telomeres for germ
      line propagation.
AB  - The chromosome-like mitotic stability of the yeast 2 micron plasmid is conferred
      by the plasmid proteins Rep1-Rep2 and the cis-acting locus STB, likely by
      promoting plasmid-chromosome association and segregation by hitchhiking. Our
      analysis reveals that stable plasmid segregation during meiosis requires the
      bouquet proteins Ndj1 and Csm4. Plasmid relocalization from the nuclear interior
      in mitotic cells to the periphery at or proximal to telomeres rises from early
      meiosis to pachytene. Analogous to chromosomes, the plasmid undergoes Csm4- and
      Ndj1-dependent rapid prophase movements with speeds comparable to those of
      telomeres. Lack of Ndj1 partially disrupts plasmid-telomere association without
      affecting plasmid colocalization with the telomere-binding protein Rap1. The
      plasmid appears to engage a meiosis-specific motor that orchestrates telomere-led
      chromosome movements for its telomere-associated segregation during meiosis I.
      This hitherto uncharacterized mode of germ-line transmission by a selfish genetic
      element signifies a mechanistic variation within the shared theme of chromosome
      coupled plasmid segregation during mitosis and meiosis. 

PMID- 24914237
TI  - BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X
      chromosome in male meiosis.
AB  - During meiosis, DNA damage response (DDR) proteins induce transcriptional
      silencing of unsynapsed chromatin, including the constitutively unsynapsed XY
      chromosomes in males. DDR proteins are also implicated in double strand break
      repair during meiotic recombination. Here, we address the function of the breast
      cancer susceptibility gene Brca1 in meiotic silencing and recombination in mice.
      Unlike in somatic cells, in which homologous recombination defects of Brca1
      mutants are rescued by 53bp1 deletion, the absence of 53BP1 did not rescue the
      meiotic failure seen in Brca1 mutant males. Further, BRCA1 promotes amplification
      and spreading of DDR components, including ATR and TOPBP1, along XY chromosome
      axes and promotes establishment of pericentric heterochromatin on the X
      chromosome. We propose that BRCA1-dependent establishment of X-pericentric
      heterochromatin is critical for XY body morphogenesis and subsequent meiotic
      progression. In contrast, BRCA1 plays a relatively minor role in meiotic
      recombination, and female Brca1 mutants are fertile. We infer that the major
      meiotic role of BRCA1 is to promote the dramatic chromatin changes required for
      formation and function of the XY body. 

PMID- 24914238
TI  - Regulation of cargo recognition, commitment, and unloading drives cotranslational
      protein targeting.
AB  - Efficient and accurate protein localization is essential to cells and requires
      protein-targeting machineries to both effectively capture the cargo in the
      cytosol and productively unload the cargo at the membrane. To understand how
      these challenges are met, we followed the interaction of translating ribosomes
      during their targeting by the signal recognition particle (SRP) using a site
      specific fluorescent probe in the nascent protein. We show that initial
      recruitment of SRP receptor (SR) selectively enhances the affinity of SRP for
      correct cargos, thus committing SRP-dependent substrates to the pathway. Real
      time measurement of cargo transfer from the targeting to translocation machinery
      revealed multiple factors that drive this event, including GTPase rearrangement
      in the SRP-SR complex, stepwise displacement of SRP from the ribosome and signal
      sequence by SecYEG, and elongation of the nascent polypeptide. Our results
      elucidate how active and sequential regulation of the SRP-cargo interaction
      drives efficient and faithful protein targeting.

PMID- 24914239
TI  - Retinal vessel calibers predict long-term microvascular complications in type 1
      diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).
AB  - Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in
      patients with type 1 diabetes, even though improvements in treatment modalities
      delay the appearance and reduce the severity of these complications. To prevent
      or further delay the onset, it is necessary to better understand common
      underlying pathogenesis and to discover preclinical biomarkers of these
      complications. Retinal vessel calibers have been associated with the presence of
      microvascular complications, but their long-term predictive value has only been
      sparsely investigated. We examined retinal vessel calibers as 16-year predictors
      of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young
      population-based Danish cohort with type 1 diabetes. We used semiautomated
      computer software to analyze vessel diameters on baseline retinal photos.
      Calibers of all vessels coursing through a zone 0.5-1 disc diameter from the disc
      margin were measured and summarized as the central artery and vein equivalents.
      In multiple regression analyses, we found wider venular diameters and smaller
      arteriolar diameters were both predictive of the 16-year development of
      nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel
      caliber changes are seemingly early markers of microvascular processes, precede
      the development of microvascular complications, and are a potential noninvasive
      predictive test on future risk of diabetic retinopathy, neuropathy, and
      nephropathy. 

PMID- 24914240
TI  - MicroRNA as potential biomarker in HCV-associated diffuse large B-cell lymphoma.
AB  - AIMS: To identify molecular characteristics to hepatitis C virus (HCV)-associated
      diffuse large B-cell lymphoma (DLBCL) through a comprehensive miRNAs expression
      profiling. METHODS: In this study, miRNA profiles were obtained from 37 patients
      with DLBCLs and 60 patients with reactive lymph nodes, equally distributed
      according to HCV presence. Germinal centres, from reactive lymph nodes were used
      as controls. Clinical features at presentation were available for all patients.
      RESULTS: A set of 52 miRNAs define a signature for HCV-associated DLBCL.
      Importantly, decreased expression of miR-138-5p and increased expression of miR
      147a, miR-147b and miR-511-5p in HCV DLBCL was found to be a poor prognostic
      factor for HCV-positive DLBCL patients. CONCLUSIONS: These data reveal molecular
      differences in diffuse DLBCL patients according to HCV presence, potentially
      useful as novel prognostic or therapeutic biomarkers.

PMID- 24914241
TI  - Different associations of diabetes with beta-cell dysfunction and insulin
      resistance among obese and nonobese Chinese women with prior gestational diabetes
      mellitus.
AB  - OBJECTIVE: To examine the relative contributions of beta-cell dysfunction and
      insulin resistance to postpartum diabetes risk among obese and nonobese women
      with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We
      performed a cross-sectional survey 1-5 years after 1,263 women who had GDM gave
      birth. Polytomous logistic regression models were used to assess the associations
      of beta-cell dysfunction (the lower quartile of HOMA-%beta), insulin resistance
      (the upper quartile of HOMA-IR), decreased insulin sensitivity (the lower
      quartile of HOMA-%S), and different categories of BMI with prediabetes and
      diabetes risk. RESULTS: beta-Cell dysfunction, insulin resistance, and decreased
      insulin sensitivity all were significantly associated with hyperglycemic status
      across normal weight, overweight, and obese groups, and the patterns of insulin
      resistance and decreased insulin sensitivity were similar. BMI was inversely
      associated with beta-cell dysfunction and positively associated with insulin
      resistance across normal glucose, prediabetes, and diabetes categories. Compared
      with women with normal glucose and weight, obese women with normal glucose had
      increased beta-cell secretory function (odds ratio [OR] 0.09 [95% CI 0.02-0.37])
      and insulin resistance (OR 17.4 [95% CI 9.47-31.9]). Normal weight diabetic women
      displayed the most beta-cell dysfunction (OR 13.6 [95% CI 4.06-45.3]), whereas
      obese diabetic women displayed the highest insulin resistance (OR 45.8 [95% CI
      18.5-113]). CONCLUSIONS: For women with prior GDM, beta-cell dysfunction had more
      pronounced contribution to postpartum diabetes among nonobese subjects, whereas
      insulin resistance contributed more to postpartum hyperglycemia among obese
      subjects.

PMID- 24914242
TI  - The association of rate of weight gain during early adulthood with the prevalence
      of subclinical coronary artery disease in recently diagnosed type 2 diabetes: the
      MAXWEL-CAD study.
AB  - OBJECTIVE: To investigate the association of the rate of weight gain (Ratemax_wt)
      between the age of 20 years and the age of maximum lifetime weight gain with
      indicators of subclinical coronary artery disease (CAD) at the time of diagnosis
      of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We studied 1,724
      consecutive Korean subjects aged >=30 years with recently diagnosed (within 3
      months) T2D and one or more cardiovascular risk factors to investigate the
      association of Ratemax_wt with subclinical CAD. We used 64-slice cardiac computed
      tomography angiography to evaluate the degree of coronary artery stenosis,
      multivessel involvement, plaque characteristics, and coronary artery calcium
      score (CACS). Body weight at age 20 years (Wt20y) was obtained from participant
      records. Participants recalled their maximum weight (Wtmax) before T2D diagnosis
      and age at maximum weight (Agemax_wt). The Ratemax_wt was calculated as (Wtmax -
      Wt20y) / (Agemax_wt - 20 years). RESULTS: The prevalence of coronary artery
      stenosis (>=50%), multivessel involvement (two or more vessels), plaque
      characteristics, and CACS >=100 were 11.4%, 6.6%, 19.7%, and 12.8%, respectively.
      Mean Wt20y and Wtmax were 60.1 +/- 10.5 and 73.0 +/- 11.5 kg, respectively. Mean
      Agemax_wt was 41.3 +/- 10.7 years, and Ratemax_wt was 0.59 +/- 0.56 kg/year.
      After adjusting for cardiovascular risk factors, including current BMI, the
      highest quarter of prior weight gain was significantly associated with coronary
      artery stenosis, multivessel involvement, and plaque characteristics,
      particularly mixed and noncalcified plaque. CONCLUSIONS: The findings suggest
      that a greater rate of prior weight gain may accelerate the development of
      subclinical vascular complications in patients with newly diagnosed T2D.

PMID- 24914243
TI  - Hypoglycemia at admission in patients with acute myocardial infarction predicts a
      higher 30-day mortality in patients with poorly controlled type 2 diabetes than
      in well-controlled patients.
AB  - OBJECTIVE: We aimed to evaluate the association between hypoglycemia at admission
      and 30-day mortality in patients with acute myocardial infarction (AMI) and to
      determine whether these associations differed according to diabetes-control
      status in AMI patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed
      the prognostic significance of hypoglycemia and hyperglycemia in 34,943 AMI
      patients with or without type 2 diabetes from two AMI registries: the Korea Acute
      Myocardial Infarction Registry (KAMIR) and the Korea Working Group on Myocardial
      Infarction (KorMI). RESULTS: The patients were divided into five groups according
      to serum-glucose levels at admission: <3.9 mmol/L (<70 mg/dL); 3.9-7.72 mmol/L
      (70-139 mg/dL); 7.78-11.06 mmol/L (140-199 mg/dL); 11.11-14.39 mmol/L (200-259
      mg/dL); and >=14.44 mmol/L (>=260 mg/dL). The 30-day mortality rates in the
      lowest and highest glucose groups were higher than those in other groups; the
      lowest glucose group had the highest mortality for patients with type 2 diabetes,
      after adjusting for multiple factors. We also extracted and compared four
      subgroups from the patients with type 2 diabetes, based on hemoglobin A1c and
      serum-glucose levels at admission: group A, <6.5% (48 mmol/mol) and <3.9 mmol/L;
      group B, <6.5% (48 mmol/mol) and >=11.11 mmol/L; group C, >=8% (64 mmol/mol) and
      <3.9 mmol/L; and group D, >=8% (64 mmol/mol) and >=11.11 mmol/L. Group C had the
      highest 30-day mortality rate among the groups. CONCLUSIONS: These data suggest
      that hypoglycemia at admission affects clinical outcomes differently in AMI
      patients with type 2 diabetes depending on the diabetes-control status.

PMID- 24914244
TI  - Incidence of pancreatitis and pancreatic cancer in a randomized controlled
      multicenter trial (SAVOR-TIMI 53) of the dipeptidyl peptidase-4 inhibitor
      saxagliptin.
AB  - OBJECTIVE: To determine the incidence of pancreatitis and pancreatic cancer in
      the SAVOR-TIMI 53 trial. RESEARCH DESIGN AND METHODS: A total of 16,492 type 2
      diabetic patients >=40 years old with established cardiovascular (CV) disease or
      CV risk factors were randomized to saxagliptin or placebo and followed for 2.1
      years. Outcome measures were investigator reported with blinded expert
      adjudication of total pancreatitis (acute and chronic) and reported cases of
      pancreatic cancer. RESULTS: Trial investigators reported 35 events of
      pancreatitis in each treatment arm in 63 patients (33 [0.40%] in the saxagliptin
      arm and 30 [0.37%] in control arm), with a hazard ratio (HR) of 1.09 (95% CI 0.66
      1.79, P = 0.80). Adjudication confirmed pancreatitis in 24 patients (26 events)
      in the saxagliptin arm (0.29%) and 21 patients (25 events) in placebo arm
      (0.26%), with an HR of 1.13 (0.63-2.06, P = 0.77). Cases of definite acute
      pancreatitis were confirmed in 17 (0.2%) vs. 9 (0.1%) (HR 1.88 [0.86-4.41], P =
      0.17), definite plus possible pancreatitis in 22 vs. 16 (HR 1.36 [0.72-2.64], P =
      0.42), and chronic pancreatitis in 2 vs. 6 (HR 0.33 [0.05-1.44], P = 0.18) in the
      saxagliptin and placebo arms, respectively. No differences in time to event
      onset, concomitant risk factors for pancreatitis, investigator-reported causality
      from study medication or disease severity, and outcome were found between
      treatment arms. The investigators reported 5 and 12 cases of pancreatic cancer in
      the saxagliptin and placebo arms, respectively (HR 0.42 [0.13-1.12], P = 0.09).
      CONCLUSIONS: In the SAVOR-TIMI 53 trial, within 2.1 years of follow-up, risk for
      pancreatitis in type 2 diabetic patients treated with saxagliptin was low and
      apparently similar to placebo, with no sign of increased risk for pancreatic
      cancer. Further studies are needed to completely resolve the pancreatic safety
      issues with incretin-based therapy.

PMID- 24914245
TI  - Oxidative metabolic pathway of lenvatinib mediated by aldehyde oxidase.
AB  - Lenvatinib is a multityrosine kinase inhibitor that inhibits vascular endothelial
      growth factor receptors, and is being developed as an anticancer drug. P450s are
      involved in one of the elimination pathways of lenvatinib, and mono-oxidized
      metabolites, such as N-oxide (M3) and desmethylated metabolite (M2), form in
      rats, dogs, monkeys, and humans. Meanwhile, two other oxidative metabolites are
      produced only in monkey and human liver S9 fractions, and their structures have
      been identified using high-resolution mass spectrometry as a quinolinone form of
      lenvatinib (M3') and a quinolinone form of desmethylated lenvatinib (M2'). The
      formation of M3' from lenvatinib occurred independently of NADPH and was
      effectively inhibited by typical inhibitors of aldehyde oxidase, indicating the
      involvement of aldehyde oxidase, but not P450s, in this pathway. M2' was a
      dioxidized metabolite arising from a combination of mono-oxidation and
      desmethylation and could only be produced from M2 in a NADPH-independent manner;
      M2' could not be generated from M3 or M3'. These results suggested that M2' is
      formed from lenvatinib by a unique two-step pathway through M2. Although both
      lenvatinib and M2 were substrates for aldehyde oxidase, an enzyme kinetic study
      indicated that M2 was a much more favorable substrate than lenvatinib. No
      inhibitory activities of lenvatinib, M2', or M3' and no significant inhibitory
      activities of M2 or M3 on aldehyde oxidase were observed, suggesting a low
      possibility of drug-drug interactions in combination therapy with substrates of
      aldehyde oxidase. 

PMID- 24914246
TI  - Efficient and Scalable Synthesis of 4-Carboxy-Pennsylvania Green Methyl Ester: A
      Hydrophobic Building Block for Fluorescent Molecular Probes.
AB  - Fluorinated fluorophores are valuable tools for studies of biological systems.
      However, amine-reactive single-isomer derivatives of these compounds are often
      very expensive. To provide an inexpensive alternative, we report a practical
      synthesis of 4-carboxy-Pennsylvania Green methyl ester. Derivatives of this
      hydrophobic fluorinated fluorophore, a hybrid of the dyes Oregon Green and Tokyo
      Green, are often cell permeable, enabling labeling of intracellular targets and
      components. Moreover, the low pKa of Pennsylvania Green (4.8) confers bright
      fluorescence in acidic cellular compartments such as endosomes, enhancing its
      utility for chemical biology investigations. To improve access to the key
      intermediate 2,7-difluoro-3,6-dihydroxyxanthen-9-one, we subjected bis-(2,4,5
      trifluorophenyl)methanone to iterative nucleophilic aromatic substitution by
      hydroxide on scales of > 40 g. This intermediate was used to prepare over 15
      grams of pure 4-carboxy-Pennsylvania Green methyl ester in 28% overall yield
      without requiring chromatography. This compound can be converted into the amine
      reactive N-hydroxysuccinimidyl ester in essentially quantitative yield for the
      synthesis of a wide variety of fluorescent molecular probes.

PMID- 24914247
TI  - The First Example of Nickel-Catalyzed Silyl-Heck Reactions: Direct Activation of
      Silyl Triflates Without Iodide Additives.
AB  - For the first time, nickel-catalyzed silyl-Heck reactions are reported. Using
      simple phosphine-supported nickel catalysts, direct activation of silyl triflates
      has been achieved. These results contrast earlier palladium-catalyzed systems,
      which require iodide additives to activate silyl-triflates. These nickel-based
      catalysts exhibit good functional group tolerance in the preparation of vinyl
      silanes, and unlike earlier systems, allows for the incorporation of
      trialkylsilanes larger than Me3Si.

PMID- 24914248
TI  - Computerized Silent Reading Rate and Strategy Instruction for Fourth Graders at
      Risk in Silent Reading Rate.
AB  - Fourth graders whose silent word reading and/or sentence reading rate was, on
      average, two-thirds standard deviation below their oral reading of real and
      pseudowords and reading comprehension accuracy were randomly assigned to
      treatment (n=7) or wait-listed (n=7) control groups. Following nine sessions
      combining computerized rapid accelerated-reading program (RAP), which
      individually tailors rate of written text presentation to comprehension criterion
      (80%), and self-regulated strategies for attending and engaging, the treated
      group significantly outperformed the wait-listed group before treatment on (a) a
      grade-normed, silent sentence reading rate task requiring lexical- and syntactic
      level processing to decide which of three sentences makes sense; and (b) RAP
      presentation rates yoked to comprehension accuracy level. Each group improved
      significantly on these same outcomes from before to after instruction. Attention
      ratings and working memory for written words predicted post-treatment accuracy,
      which correlated significantly with the silent sentence reading rate score.
      Implications are discussed for (a) preventing silent reading disabilities during
      the transition to increasing emphasis on silent reading, (b) evidence-based
      approaches for making accommodation of extra time on timed tests requiring silent
      reading, and

PMID- 24914250
TI  - Benchmarking critical care processes: Reaching standards of excellence!

PMID- 24914249
TI  - The role of IL-17 promotes spinal cord neuroinflammation via activation of the
      transcription factor STAT3 after spinal cord injury in the rat.
AB  - STUDY DESIGN: In this study, we investigated the role of IL-17 via activation of
      STAT3 in the pathophysiology of SCI. OBJECTIVE: The purpose of the experiments is
      to study the expression of IL-17 and related cytokines via STAT3 signaling
      pathways, which is caused by the acute inflammatory response following SCI in
      different periods via establishing an acute SCI model in rat. METHODS: Basso,
      Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the
      rat hind limb motor function. Immunohistochemistry was used to determine the
      expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting
      analysis was used to determine the protein expression of p-STAT3 in spinal cord
      tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in
      the spleen tissue. ELISA was used to determine the peripheral blood serum levels
      of IL-6, IL-21, and IL-23. RESULTS: Compared to the sham-operated group, the
      expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly
      increased and peaked at 24 h after SCI. The increased levels of cytokines were
      correlated with the SCI disease stages. CONCLUSION: IL-17 may play an important
      role in promoting spinal cord neuroinflammation after SCI via activation of
      STAT3.

PMID- 24914251
TI  - Translating intentions to prescriptions: Mind the gap!

PMID- 24914252
TI  - Association between glycemic variability and mortality: How robust is the
      evidence?

PMID- 24914253
TI  - Dexmedetomidine: Toward a paradigm shift in ICU sedation.

PMID- 24914254
TI  - A prolonged observational study of tracheal tube displacements: Benchmarking an
      incidence <0.5-1% in a medical-surgical adult intensive care unit.
AB  - BACKGROUND AND AIMS: Tracheal tubes are commonly used in intensive care unit
      (ICU) and lead to complications like displacements. The primary aim of the study
      was to evaluate if the rate of tracheal tube displacement benchmarked at <1% per
      patient and <0.5% per tracheal tube day, could be sustained over a prolonged
      period. The secondary aim was to document the patterns of all forms airway
      accident and to evaluate their consequences. SUBJECTS AND METHODS: This was a
      prospective observational study of Intubated and ventilated patients in a General
      Medical-Surgical Adult ICU. The incidence of accidental extubation, self
      extubation, partial displacement and blockages of tracheal tubes were recorded.
      RESULTS: The overall tracheal tube displacement rate was 61/10,112 (0.6%) per
      patient and 61/28,464 (0.22%) per tracheal tube day. There were 30 additional
      incidents of blockage, kinking or biting of the tracheal tube. Physiological
      consequences-69 were mild, 10 moderate, 12 major and one death. Of the 91
      accidents, 30 were partly and 30 were completely preventable. 76 incidents
      involved an endotracheal tube (54 displaced, 12 blocked and 10 bitten-kinked) and
      15 a tracheostomy tube (seven displaced and eight blocked). Accidents were more
      common in medical than surgical patients (medical = 48, cardiac surgical = 17 and
      other surgical/trauma = 26). CONCLUSION: Tracheal tube displacement rate in a
      mixed medical-surgical adult ICU was maintained below the pre-set benchmark of
      <1% per patient and <0.5% per intubated day over nearly a decade.

PMID- 24914255
TI  - Evaluation of rationality in prescribing, adherence to treatment guidelines, and
      direct cost of treatment in intensive cardiac care unit: A prospective
      observational study.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) remain the most common cause of sudden
      death. Hence, appropriate drug therapy in intensive cardiac care unit (ICCU) is
      crucial in managing cardiovascular emergencies and to decrease morbidity and
      mortality. OBJECTIVE: To evaluate prescribing pattern of drugs and direct cost of
      therapy in patients admitted in ICCU. MATERIALS AND METHODS: Patients admitted in
      ICCU of a tertiary care teaching hospital were enrolled. Demographic data,
      clinical history, and complete drug therapy received during their stay in ICCU
      were noted. Data were analyzed for drug utilization pattern and direct cost of
      treatment calculated using patient's hospital and pharmacy bills. Rationality of
      therapy was evaluated based on American College of Cardiology/American Heart
      Association (ACC/AHA) guidelines. RESULT: Data of 170 patients were collected
      over 2 months. Mean age of patients was 54.67 +/- 13.42 years. Male to female
      ratio was 2.33:1. Most common comorbid condition was hypertension 76 (44.7%).
      Most common diagnosis was acute coronary syndrome (ACS) 49.4%. Mean stay in ICCU
      was 4.42 +/- 1.9 days. Mean number of drugs prescribed per patient was 11.43 +/-
      2.85. Antiplatelet drugs were the most frequently prescribed drug group (86.5%).
      Mean cost of pharmacotherapy per patient was '2701.24 +/- 3111.94. Mean direct
      cost of treatment per patient was '10564.74 +/- 14968.70. Parenteral drugs
      constituted 42% of total drugs and 90% of total cost of pharmacotherapy. Cost of
      pharmacotherapy was positively correlated with number of drugs (P = 0.000) and
      duration of stay (P = 0.027). CONCLUSION: Antiplatelet drugs were the most
      frequently prescribed drug group. Mean number of drugs per encounter were high,
      which contributed to the higher cost of pharmacotherapy. ACC/AHA guidelines were
      followed in majority of the cases.

PMID- 24914256
TI  - Glycemic variability and outcome in critically ill.
AB  - BACKGROUND: Acute hyperglycemia, hypoglycemia and glycemic variability (GV) have
      been found to be the three principal domains of glycemic control, which can
      adversely affect patient outcome. GV may be the confounding factor in tight
      glycemic control trials in surgical and medical patient. OBJECTIVE: This study
      was conducted to establish if there was any relationship between GV and intensive
      care unit (ICU) mortality in the Indian context. STUDY DESIGN: A retrospective
      review of a large cohort of prospectively collected database. SETTING: Adult
      Medical/Surgical/Trauma/Neuro ICU of a tertiary care hospital. PATIENT
      POPULATION: All patients who had four or more blood glucose measured during the
      ICU stay. OUTCOME: ICU mortality. RESULT: 2208 patients with a total of 11,335
      blood glucose values were analyzed. GV measured by the standard deviation (SD) of
      mean blood glucose and glycemic lability index (GLI), both were significantly (P
      < 0.001) associated with ICU mortality. This relationship was maintained (odds
      ratio (OR): 2.023, 95% confidence interval (CI): 1.483-2.758) even after
      excluding patients with hypoglycemia (<60 mg/dl). Patients with blood glucose
      values in the euglycemic range but highest SD had higher mortality (54%) compared
      to mortality (24%) in patients above the euglycemic range. Similarly patients
      with blood sugar values below the average for study cohort and high GLI, another
      marker of GV had higher mortality (OR: 5.62, CI: 3.865-8.198) than compared to
      patients in the hyperglycemic range, reflecting the importance of GV as a
      prognostic marker in patients with blood sugar in the euglycemic range.
      CONCLUSION: This study demonstrated that high glucose variability is associated
      with increased ICU mortality in a large heterogeneous cohort of ICU patients.
      This effect was particularly evident among patients in the euglycemic range.

PMID- 24914257
TI  - Comparison of post-operative ICU sedation between dexmedetomidine and propofol in
      Indian population.
AB  - CONTEXT: Critically ill patients requiring mechanical ventilation frequently need
      sedatives and analgesics to facilitate their care. Dexmedetomidine, a short
      acting alpha-2-agonist, possesses anxiolytic, anesthetic, hypnotic, and analgesic
      properties. AIMS: The objective of this study was to evaluate the efficacy and
      safety of dexmedetomidine in comparison to propofol in the management of sedation
      for post-operative intensive care unit (ICU) patients, as a sedative agent.
      SETTINGS AND DESIGN: Teaching hospital, A phase III, prospective, open,
      randomized and comparative. MATERIALS AND METHODS: Thirty patients who were
      ambulatory and who required the post-operative mechanical ventilation or post
      operative sedation were enrolled, in which 15 patients received Dexmedetomidine
      and remaining 15 patients received propofol. All these patients were treated for
      the period of 8 to 24 h. STATISTICAL ANALYSIS USED: Data were analyzed using
      Student's t-test and Chi-square test. The value of P < 0.05 was considered as
      statistically significant. RESULTS: Demographic data were comparable. Pulse rate,
      respiratory rate and blood pressure were comparable. Depth of sedation and
      extubation time were similar. To maintain analgesia throughout the study period,
      patients receiving propofol infusions required significantly more analgesics than
      patients receiving Dexmedetomidine. CONCLUSIONS: Dexmedetomidine appears to be a
      safe and acceptable ICU sedative agent when both the clinician's and patient's
      perspectives are considered.

PMID- 24914258
TI  - To identify morbidity and mortality predictors in acute organophosphate
      poisoning.
AB  - BACKGROUND: Organophosphorus poisoning remains an important cause of morbidity
      and mortality, but no definite parameters have been identified as predictors of
      outcome. Prediction of morbidity at presentation might help in decision making in
      places of limited resources like rural settings in developing countries.
      MATERIALS AND METHODS: A total of 76 cases were included in this retrospective
      cohort study. Logged relative risk of requirement of mechanical ventilation and
      hospital stay >7 days was measured in patients with serum acetylcholinesterase
      (s. acetylcholinesterase) <1000 versus >1000, presenting in <2 h versus >= 2 h
      after exposure, with Glasgow Coma Scale (GCS) <=12 versus >12 and in patients
      with SpO2 <85% versus >=85% at room air at presentation. RESULTS: S.
      acetylcholinesterase <1000, time elapsed after ingestion to presentation >= 2 h
      and SpO2 (at room air) at presentation <85% were found to have positive
      association with requirement of ventilation. GCS <= 12 had a significant
      association with both requirement of ventilation and hospital stay >7 days.
      CONCLUSION: S. acetylcholinesterase, SpO2 at room air, GCS, and duration of
      exposure at presentation can be used to identify the requirement of special care
      in acute organophosphorus poisoning. This can aid in decision making regarding
      admission to intensive care unit and referral in the places with limited
      resources.

PMID- 24914259
TI  - Bedside ultrasonography: Applications in critical care: Part I.
AB  - There is increasing interest in the use of ultrasound to assess and guide the
      management of critically ill patients. The ability to carry out quick
      examinations by the bedside to answer specific clinical queries as well as
      repeatability are clear advantages in an acute care setting. In addition, delays
      associated with transfer of patients out of the Intensive Care Unit (ICU) and
      exposure to ionizing radiation may also be avoided. Ultrasonographic imaging
      looks set to evolve and complement clinical examination of acutely ill patients,
      offering quick answers by the bedside. In this two-part narrative review, we
      describe the applications of ultrasonography with a special focus on the
      management of the critically ill. Part I explores the utility of echocardiography
      in the ICU, with emphasis on its usefulness in the management of hemodynamically
      unstable patients. We also discuss lung ultrasonography - a vastly underutilized
      technology for several years, until intensivists began to realize its usefulness,
      and obvious advantages over chest radiography. Ultrasonography is rapidly
      emerging as an important tool in the hands of intensive care physicians. 

PMID- 24914260
TI  - Current concepts in combination antibiotic therapy for critically ill patients.
AB  - Widespread emergence of multidrug resistant (MDR) bacterial pathogens is a
      problem of global dimension. MDR infections are difficult to treat and frequently
      associated with high mortality. More than one antibiotic is commonly used to
      treat such infections, but scientific evidence does not favor use of combination
      therapy in most cases. However, there are certain subgroups where combination
      therapy may be beneficial, e.g. sepsis due to carbapenem-resistant
      Enterobacteriaceae (CRE), bacteremic pneumococcal pneumonia, and patients with
      multiple organ failure. Well-designed prospective studies are needed to clearly
      define the role of combination therapy in these subgroups. 

PMID- 24914261
TI  - Fatal adverse drug reactions: Experience of adverse drug reactions in a tertiary
      care teaching hospital of North India - A case series.
AB  - Medical burden of fatal adverse drug reactions (FADRs) is significant. The
      epidemiological data on FADR do exist from the western world, but there is scanty
      from India. We hereby report a case series of FADRs recorded in a 2 years period.
      Point prevalence of FADRs was 0.223%. Point prevalence of all cause death in the
      hospital was 1.20%. The drugs causing FADRs were injection bupivacaine,
      amphotericin B, directly observed treatment short-course Category-1, injection
      streptokinase, and tablet ferrous sulfate. All these FADR were labeled as
      possible expect one case as probable. All FADR were labeled as type A. In three
      out of five the central nervous system was involved, while the hepatic system and
      multiorgan failure accounted for one case each. Two cases each were acute and
      subacute, while one was latent in nature. Reporting of FADRs shall go a long way
      in patient safety. 

PMID- 24914263
TI  - Invasive pulmonary aspergillosis in an immunocompetent patient with severe dengue
      fever.
AB  - We report a case of a 65-year-old female diagnosed with sever dengue fever. She
      started showing recovery from dengue fever with medical management. On day 6 of
      admission, she had leukocytosis, altered mental sensorium, and hemoptysis. Chest
      tomography showed air space consolidation with multiple nodules in the left upper
      and middle lobe sputum and bronchoalveolar lavage cultures were positive for
      Aspergillus flavus. The patient showed improvement with voriconazole and therapy
      was continued for 6 weeks. 

PMID- 24914262
TI  - Urinothorax: A rare cause of severe respiratory distress.
AB  - A case of massive right pleural effusion in a postoperative patient of
      percutaneous nephrolithotomy leading to severe respiratory distress is reported.
      A high degree of clinical suspicion and prompt intervention by insertion of an
      intercostal drainage tube prevented the patient from going in to respiratory
      failure. The development of arrhythmias confused the picture increasing the
      morbidity of the patient. However, the patient was managed in an intensive care
      unit with intercostal chest tube insertion and antiarrhythmic agents. After
      correction of the specific cause of the effusion the intercostal tube was removed
      on the 4(th) day without further recurrence of the effusion. 

PMID- 24914264
TI  - Shock: A possible presenting manifestation of autoimmune polyendocrine syndrome
      type II.
AB  - Autoimmune polyendocrine syndrome Type II (APS II), also known as polyglandular
      autoimmune syndrome Type II or Schmidt syndrome, is constellations of multiple
      endocrine gland insufficiencies. It is a rare, but most common of the
      immunoendocrinopathy syndrome. It is characterized by the obligatory occurrence
      of autoimmune Addison's disease in combination with thyroid autoimmune diseases
      and/or Type I diabetes, hypogonadism, hypophysitis, myasthenia gravis, vitiligo,
      alopecia, pernicious anemia, and celiac disease. Here, we report a case of 38
      year-old female patient presented with shock, further diagnosed to have APS II. 

PMID- 24914265
TI  - Glyphosate surfactant herbicide poisoning and management.
AB  - Glyphosate is a widely used herbicide in agriculture, forestry, industrial weed
      control and aquatic environments. Glyphosate potential as herbicide was first
      reported in 1971. It is a non-selective herbicide. It can cause a wide range of
      clinical manifestations in human beings like skin and throat irritation to
      hypotension, oliguria and death. We are reporting a case of a 35-year-old male
      patient who was admitted to our tertiary care hospital following intentional
      ingestion of around 200 ml of herbicide containing glyphosate. Initially, gastric
      lavage done and the patient was managed with intubation and mechanical
      ventilation, noradrenaline and vasopressin infusion, continuous veno-venous
      hemodiafiltration and intravenous (IV) lipid emulsion (20% intralipid 100 ml),
      patient was successfully treated and discharged home. This case report emphasizes
      on timely systemic supportive measure as a sole method of treatment since this
      poison has no known specific antidote and the use of IV lipid emulsion for a
      successful outcome. 

PMID- 24914266
TI  - Apnea testing with continuous positive airway pressure for the diagnosis of brain
      death in a patient with poor baseline oxygenation status.
AB  - Apnea testing is a key component in the clinical diagnosis of brain death.
      Patients with poor baseline oxygenation may not tolerate the standard 8-10 min
      apnea testing with oxygen insufflation through tracheal tube. No studies have
      assessed the safety and feasibility of other methods of oxygenation during apnea
      testing in these types of patients. Here, we safely performed apnea testing in a
      patient with baseline PaO2 of 99.1 mm Hg at 100% oxygen. We used continuous
      positive airway pressure (CPAP) of 10 cm of H2O and 100% oxygen at the flow rate
      of 12 L/min using the circle system of anesthesia machine. After 10 min of apnea
      testing, PaO2 decreased to 75.7 mm Hg. There was a significant rise in PaCO2 and
      fall in pH, but without hemodynamic instability, arrhythmias, or desaturation.
      Thus, the apnea test was declared positive. CPAP can be a valuable, feasible and
      safe means of oxygenation during apnea testing in patients with poor baseline
      oxygenation, thus avoiding the need for ancillary tests. 

PMID- 24914267
TI  - Rhino-orbito-cerebral mucormycosis in a child with diabetic ketoacidosis.

PMID- 24914268
TI  - Curious association between Plasmodium vivax malaria and nontraumatic acute
      subdural hematoma.

PMID- 24914269
TI  - Burnout in the intensive care unit: Beware of turning to ash!

PMID- 24914270
TI  - 2009 pandemic influenza A (H1N1) infection in Saurashtra region, India.

PMID- 24914271
TI  - Author's Reply.

PMID- 24914272
TI  - Study on interaction between plasmid DNA and berberine derivatives with aliphatic
      chain by fluorescence analysis.
AB  - In this study, the fluorescence analysis was used to reveal the interaction
      between berberine derivatives and plasmid DNA. The results showed that berberine
      (C0) and its 8-alkyl derivatives can enhance the fluorescent intensity of plasmid
      DNA. Compared with 8-dodecyl- (C12) and 8-hexadecyl- (C16) berberine, 8
      alkylberberine with shorter alkyl group, such as 8-ethyl (C2), 8-butyl (C4), 8
      hexyl (C6), and 8-octyl (C8) berberine derivatives showed higher fluorescence
      increasing effect. Among all compounds, C4 showed highest fluorescence increasing
      effect. All compounds tested obviously enhanced fluorescent intensity at the
      concentration of 6.25 * 10(-5) mol/L. These results suggested that berberine and
      its derivatives can be selectively inserted to the grooves running down the
      plasmid DNA helix, thus, lead to the increase of fluorescence intensity of the
      reaction system. Also, adding proper length of aliphatic chain to berberine could
      promote the interaction between DNA and berberine derivatives. The results of
      this study may lay some useful foundation for the development of berberine-based
      medicine agents. 

PMID- 24914273
TI  - Analysis of the metabolites of mesaconitine in rat blood using ultrafast liquid
      chromatography and electrospray ionization mass spectrometry.
AB  - BACKGROUND: Mesaconitine is the main active component of genus aconitum plants
      that are widely used in clinics in China. However, little has been known about
      the metabolic pathway of mesaconitine. OBJECTIVE: To explore the metabolites and
      propose the pathway of mesaconitine. MATERIALS AND METHODS: In the present study,
      mesaconitine (4 mg kg(-1)) was orally administered to male rats. Then, blood
      samples collected were pretreated using solid-phase extraction technique with C18
      cartridges, and analyzed using LC/MS/MS method with electrospray ionization. Both
      positive ion mode and collision induced dissociation (CID) were used to elucidate
      the structures of the major metabolites of mesaconitine. RESULTS: Ten compounds
      were identified, among which seven were new metabolites, and the metabolic
      pathway was proposed. The protonated molecular ions of seven new metabolites were
      at m/z 648, 618, 616, 602, 572, 468, and 542, multistage fragment ions with
      neutral loss of 28 u (CO), 60 u (CH3COOH), 18 u (H2O), and 32 u (CH3OH). These
      new metabolites detected firstly in vivo, were named 10-hydroxyl-mesaconitine,
      hypaconitine, dehydrated mesaconitine 16-O-demethylmesaconitine, 16-O
      demethylhypaconitine, and 16-O-demethyl-dehydrated hypaconitine, respectively.
      Furthermore, the breaking sequence of methoxyl was obtained using quantum
      chemistry. CONCLUSION: The study proved that the method of solid-phase extraction
      technique coupled with MS and quantum chemistry can be applied to the analysis of
      metabolites in plasma quickly and conveniently.

PMID- 24914274
TI  - Protective effects of curcumin against genotoxicity induced by 131-iodine in
      human cultured lymphocyte cells.
AB  - BACKGROUND: 131-radioiodine has been widely used as an effective radionuclide for
      treatment of patients with thyroid diseases. The purpose of the present study is
      to investigate the radioprotective effects of curcumin as a natural product that
      protects against the genotoxic effects of (131)I in human cultured lymphocytes.
      MATERIALS AND METHODS: Whole blood samples from human volunteers were incubated
      with curcumin at doses of 5, 10, and 50 MUg/mL. After 1-hour incubation, the
      lymphocytes were incubated with (131)I (100 MUCi/1.5 ml) for 2 hours. The
      lymphocyte cultures were then mitogenically stimulated to allow for evaluation of
      the number of micronuclei in cytokinesis-blocked binucleated cells. RESULTS:
      Incubation of lymphocytes with (131)I at dose 100 MUCi/1.5 mL induced
      genotoxicity shown by increase in micronuclei frequency in human lymphocytes.
      Curcumin at 5, 10, and 50 MUg/mL doses significantly reduced the micronuclei
      frequency. Maximal protective effects and greatest decrease in micronuclei
      frequency were observed when whole blood was incubated with 50 MUg/mL dose of
      curcumin with 52%. CONCLUSION: This study has important implications for patients
      undergoing (131)I therapy. Our results indicate a protective role for curcumin
      against the genetic damage and side effects induced by (131)I administration.

PMID- 24914275
TI  - ACE and platelet aggregation inhibitors from Tamarix hohenackeri Bunge (host
      plant of Herba Cistanches) growing in Xinjiang.
AB  - BACKGROUND: Tamarix hohenackeri Bunge is a salt cedar that grows widespread in
      the desert mountains in Xinjiang. T. hohenackeri has not been investigated
      earlier, although there are many reports of phytochemical work on other Tamarix
      species. MATERIALS AND METHODS: To find out natural angiotensin-converting enzyme
      (ACE) inhibitor and platelet aggregation inhibitors, the bioactive extract (ethyl
      acetate [EtOAc] fraction) from the dried aerial parts of T. hohenackeri were
      investigated. The active fraction was purified by repeated column chromatography,
      including silica gel, Sephadex LH-20 column, medium-pressure liquid
      chromatography (MPLC) (polyamide column) and high-performance liquid
      chromatography (HPLC). The isolated major constituents were tested for their anti
      platelet aggregation activity. RESULTS: Bioassay-directed separation of the EtOAc
      fraction of the 70% ethanol extract from the air-dried aerial parts of T.
      hohenackeri led to the isolation of a new triterpenoid lactone (1), together with
      13 known compounds (2-14). It was the first time to focus on screening bioactive
      constituents for this plant. The chemical structures were established on the
      basis of spectral data (ESI-MS and NMR). The results showed that the flavonoid
      compounds (7 and 8) and phenolic compounds (9, 10, 11, and 14) were potential ACE
      inhibitors. And the flavonoid compounds (5 and 7) showed significant anti
      platelet aggregation activities. CONCLUSION: On the basis of the chemical and
      biological data, the material basis of ACE inhibitory activity for the active
      part was the phenolic constituents. However, the flavonoid compounds were
      responsible for the anti-platelet aggregation. The primary structure and activity
      relationship were also discussed respectively.

PMID- 24914276
TI  - Leucas aspera inhibits the Dalton's ascitic lymphoma in Swiss albino mice: A
      preliminary study exploring possible mechanism of action.
AB  - BACKGROUND: North East India is a rich source of medicinal plants and a number of
      plant extracts are used by tribal peoples living in this area for various
      disorders. L.aspera is such a plant, traditionally used as an antitumor agent.
      AIM: In the present study, aerial parts of L.aspera were investigated for
      antitumor activity in Dalton's lymphoma (DAL) bearing mice. The ability of plant
      extract in free radical scavenging, neoangiogenesis inhibition and macrophage
      stimulation were also checked. MATERIALS AND METHODS: Based on the preliminary in
      vitro cytotoxicity studies ethyl acetate fraction of L.aspera (EALA) was selected
      for the detailed study. DAL ascites tumor model was performed to check the
      antitumor activity of EALA (200 and 400mg/kg of body weight). Hematological and
      histopathological parameters were estimated. Antioxidant levels, neoangiogenesis
      and peritoneal macrophage count were also determined. RESULTS: In vitro MTT and
      Trypan blue assay results showed the cytotoxic effect of EALA in DAL cells lines.
      EALA treatment resulted in significant decrease in ascites tumor volume and
      viable cell count. Hematological and liver antioxidant parameters were normalised
      by EALA treatment. It was also found that EALA treatment inhibits
      neovascularisation and produce macrophage stimulation in treated mice.
      CONCLUSION: The results showed that EALA is a promising anticancer agent and its
      activity is comparable to the standard drug 5-Flouro uracil (5-FU).

PMID- 24914277
TI  - The extracts of Japanese willow tree species are effective forapoptotic
      desperation or differentiation of acute myeloid leukemia cells.
AB  - BACKGROUND: The antileukemic activity of hot water extract of plant parts of some
      Japanese willow tree species grown at different levels of nitrogen were examined.
      MATERIALS AND METHODS: Water extracts of willow leaves were prepared for this
      studies in different level of nitrogen nutrition. RESULTS: The extracts obtained
      from the leaves and stem exhibited anti-leukemic activities prominently. The
      crude hot water extracts of the young growing parts including apex, matured
      leaves and stem, killed the blasts of acute myeloid leukemia (AML) cells, (HL60
      and NB4) after 48h incubation, however, such desperation was far less in the root
      extract. Similar to the plant parts, response of extracts obtained from different
      willow species was not identical; the proportion of dead cells relative to whole
      cells of the culture medium ranged from 21% to 93% among the species. Leaf
      extracts obtained from the responsive willow species decreased the live cell
      percentage and increased the dead cell percentage at higher level of nitrogen
      nutrition. The mode of desperation of leaf extract treated AML cells in such
      species appeared to be cell apoptosis as shown by binding with fluorescein
      isothiocyanate (FITC) -labeled Annexin V. CONCLUSION: Differentiation of alive
      AML cells continued unabated and apoptosis was poor when extract of an
      unresponsive species added to the culture medium.

PMID- 24914279
TI  - Study on the in vivo toxic mechanism of xixin based on trace elements
      determination by inductively coupled plasma-mass spectrometry.
AB  - BACKGROUND: Xixin has been widely used as a traditional Chinese medicine for
      headache, toothache and inflammatory diseases. Clinical investigation indicated
      that adverse drug reactions occurred with an overdose of xixin, but the toxic
      mechanism of xixin in vivo based on trace elements has not been researched yet.
      OBJECTIVE: To explore the in vivo toxic mechanism of xixin induced by trace
      elements. MATERIALS AND METHODS: The contents of trace elements in the serum and
      liver of mice were determined by inductively coupled plasma-mass spectrometry
      (ICP-MS) after obtaining xixin extracts. Principal component analysis (PCA) and
      cluster analysis (CA) were performed between the trace elements' content and
      dosage using the software GeneSpring 12.1 to analyze the main toxic elements in
      vivo. RESULTS: Trace elements' contents were obviously raised after xixin
      extracts were taken as a dosage of 150 mg/mL and 50 mg/mL, respectively. Na, Ca,
      Cu and Cd in serum and Ca and Zn in liver were the main trace elements inducing
      the toxic reaction of xixin. CONCLUSION: Xixin possesses the potential function
      of indirectly upregulating trace elements in vivo. This study, for the first
      time, elucidated the in vivo toxic mechanism of xixin based on trace elements.
      This method could also be utilized in the research of corresponding aspects.

PMID- 24914278
TI  - Effect of Aronia melanocarpa fruit juice on amiodarone-induced pneumotoxicity in
      rats.
AB  - BACKGROUND: The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in
      biologically active polyphenols. OBJECTIVE: We studied the protective effect of
      A. melanocarpa fruit juice (AMFJ) in a model of amiodarone (AD)-induced
      pneumotoxicity in rats. MATERIALS AND METHODS: AD was instilled intratracheally
      on days 0 and 2 (6.25 mg/kg). AMFJ (5 mL/kg and 10 mL/kg) was given orally from
      day 1 to days 2, 4, 9, and 10 to rats, which were sacrificed respectively on days
      3, 5, 10, and 28 when biochemical, cytological, and immunological assays were
      performed. RESULTS: AMFJ antagonized AD-induced increase of the lung weight
      coefficient. In bronchoalveolar lavage fluid, AD increased significantly the
      protein content, total cell count, polymorphonuclear cells, lymphocytes and the
      activity of lactate dehydrogenase, acid phosphatase and alkaline phosphatase on
      days 3 and 5. In AMFJ-treated rats these indices of direct toxic damage did not
      differ significantly from the control values. In lung tissue, AD induced
      oxidative stress measured by malondialdehyde content and fibrosis assessed by the
      hydroxyproline level. AMFJ prevented these effects of AD. In rat serum, AD caused
      a significant elevation of interleukin IL-6 on days 3 and 5, and a decrease of IL
      10 on day 3. In AMFJ-treated rats, these indices of inflammation had values that
      did not differ significantly from the control ones. CONCLUSION: AMFJ could have a
      protective effect against AD-induced pulmonary toxicity as evidenced by the
      reduced signs of AD-induced direct toxic damage, oxidative stress, inflammation,
      and fibrosis.

PMID- 24914280
TI  - Pretreatment with Assafoetida exerts dose-dependent dual effects on rat hearts.
AB  - CONTEXT: Although many studies displayed the favorable effects of Assafoetida,
      some of them reported that high doses of Assafoetida could lead to harmful
      effects. AIMS: In this study, the effect of pretreatment with Assafoetida
      investigated on ischemic-reperfusion injury in isolated rat heart model.
      MATERIALS AND METHODS: Thirty two male Wistar rats were divided into 4 groups of
      eight. Group 1 as the control (Con) group and three other groups as the treatment
      groups that given Assafoetida by gavage at levels of 25, 50 and 100 mg/kg, once a
      day for four weeks (T25, T50 and T100 groups). Then their hearts were subjected
      to 30 min global ischemia and 90 min reperfusion under langendorff apparatus.
      RESULTS: The data shown that hemodynamic parameters including left ventricular
      developed pressure (LVDP) and maximum and minimum of pressure changes (+/-dp/dt)
      were increased in T25 and decreased in T50 and T100 groups during reperfusion in
      comparison with Con group. There was not any significant difference in the
      incidence of irreversible ventricular fibrillation between T25 and Con group,
      while it was increased in T50 and T100 groups significantly. There was not any
      significant difference in infarct size between all groups. CONCLUSION: These data
      indicate that pretreatment of rats with Assafoetida have cardioprotective effects
      in low doses and cardiotoxic effects in higher doses. Therefore, it needs more
      investigation in the future.

PMID- 24914281
TI  - Podophyllotoxin and 6-methoxy podophyllotoxin Production in Hairy Root Cultures
      of Liunm mucronatum ssp. mucronatum.
AB  - AIM: Two bacterial strains of Agrobacterium rhizogenes, A13 and 9534 were
      evaluated for induction of transformed hairy roots in Linum mucronatum ssp.
      mucronatum, a high value medicinal plant. MATERIALS AND METHODS: The hairy roots
      were successfully initiated, through infecting the hypocotyl and root explants
      and the A13 strain performed a high transformation frequency for hairy roots
      induction. Transgenic status of hairy roots was confirmed by polymerase chain
      reaction (PCR) analysis of the rol genes. Growth kinetics of transgenic roots
      induced by two strains indicated a similar pattern of growth, with maximum growth
      occurring between 42 to 56 days. The lignan contents in hairy roots were analyzed
      using high-performance liquid chromatography (HPLC) method. RESULTS: Transformed
      cultures showed significant differences (P < 0.05) in lignan content. The highest
      amount of Podophyllotoxin (PTOX, 5.78 mg/g DW) and 6-methoxy podophyllotoxin
      (MPTOX, 49.19 mg/g DW) was found in transformed lines induced by strain A13,
      which was four times higher than those of non-transformed roots. The results
      showed that hairy root cultures of L. mucronatum are rich sources of MPTOX.
      CONCLUSION: hairy root cultures from L. mucronatum can be used as a useful system
      for scale-up producing MPTOX and precursors for the production of antitumor
      agents in substitution with PTOX by considering the appropriate optimizations in
      future studies.

PMID- 24914282
TI  - Neuroprotective effects of 4,5-dimethoxypyrocatechol isolated from Cynanchum
      paniculatum on HT22 cells.
AB  - BACKGROUND: Cynanchum paniculatum, belongs to the family Asclepiadaceae and is
      used to treat various diseases, such as invigorate blood, alleviate edema and to
      relieve pain and toxicity for a long time. MATERIALS AND METHODS: 4,5
      Dimethoxypyrocatechol was isolated from the 80% methanol extract of C.
      paniculatum and its neuroprotective effect was evaluated by MTT assay. RESULTS:
      4,5-Dimethoxypyrocatechol had neuroprotective effect on the glutamate-induced
      cellular oxidative death in HT22 cells. CONCLUSION: Furthermore, we found that
      reactive oxygen species (ROS) accumulation and calcium concentration by oxidative
      stress were reduced by 4,5-dimethoxypyrocatechol in HT22 cells.

PMID- 24914283
TI  - Effect of ambrex (a herbal formulation) on oxidative stress in hyperlipidemic
      rats and differentiation of 3T3-L1 preadipocytes.
AB  - BACKGROUND: Ambrex is a polyherbal formulation which consists of Withania
      somnifera, Orchis mascula, Cycas circirnalis, Shorea robusta with amber.
      OBJECTIVE: The present study was designed to explore the potential effects of
      ambrex on the antioxidant status in high fat diet fed rats and to investigate the
      possible mechanisms focusing on the gene expression involved in adipogenesis and
      inflammation in 3T3-L1 cell line. MATERIALS AND METHODS: Male Wistar rats were
      divided into four groups (n = 6); Group A received normal diet, Group B received
      high fat diet for 30 days, Group C and D received high fat diet for 30 days and
      treated with ambrex (40 mg/kg b.w) and atorvastatin (10 mg/kg b.w) for successive
      15 days respectively. This study also assesses the effect of ambrex on
      adipogenesis in 3T3-L1 adipocytes. RESULTS: The serum total cholesterol and
      triglycerides were significantly decreased in ambrex treated hyperlipidemic
      animals when compared to untreated animals. The activities of catalase,
      superoxide dismutase and reduced glutathione were significantly augmented in the
      serum, liver, and heart of hyperlipidemic rats treated with ambrex when compared
      to control. Ambrex treated rats had significant reductions in malondiadehyde
      levels in the serum, liver and heart compared to untreated rats. In addition, we
      observed that treatment with ambrex resulted in a major inhibition of pre
      adipocyte differentiation of 3T3-L1 cells in vitro by suppression of peroxisome
      proliferator activated receptor gamma, sterol regulatory binding proteins, tumor
      necrosis factor-alpha, inducible nitricoxide synthase, leptin, and upregulation
      of thioredoxin 1 (TRX1) and TRX2 mRNA expression. CONCLUSION: Therefore, ambrex
      may be a potential drug for treatment of hyperlipidemia and related disorders.

PMID- 24914284
TI  - Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced
      diabetic cardiomyopathy in rats.
AB  - Diabetes mellitus (DM) is a complex metabolic disorder which leads to development
      of various long-term complications including cardiomyopathy. Oxidative stress due
      to hyperglycemia plays a key role in the development and progression of diabetic
      cardiomyopathy (DC). Oxidative stress causes the opening of mitochondrial
      permeability transition pore (mPTP) eventually leading to myocardium dysfunction.
      The Ginkgo biloba extract (EGb 761) has antioxidant and mitochondrial membrane
      potential stabilizing property. Therefore, this study was designed to evaluate
      the effect of EGb 761 and its possible mechanism of action in DC. MATERIALS AND
      METHODS: DM was induced by single injection of Streptozotocin (STZ) (50 mg/kg,
      i.p.) and cardiac dysfunction was developed on 8(th) weeks after STZ injection.
      Cardiac dysfunction was assessed by measuring left ventricle weight/body weight
      (LVW/BW) ratio, left ventricle (LV) collagen content, LV protein content, serum
      lactate dehydrogenase (LDH) level. RESULTS: EGb 761 treatment (started after
      7(th) week of STZ injection and continued for 3 weeks) attenuated cardiac
      dysfunction in diabetic rats as evidenced by a decrease in LV collagen content,
      protein content, LVW/BW ratio, serum LDH level. Moreover, EGb 761 attenuated the
      oxido-nitrosative stress (thiobarbituric acid reactive substances, superoxide
      anion generation, myocardium nitrite) and concomitantly improved the antioxidant
      enzyme (reduced glutathione) level as compared to untreated diabetic rats.
      However, protective effect of EGb 761 was inhibited by atractyloside (mPTP
      opener) that was given for 3 weeks, 30 min before the EGb 761 treatment. These
      results indicate that EGb 761 corrects diabetic cardiac dysfunction probably by
      its direct radical scavenging activity and its ability to inhibit the opening of
      mPTP channel since the cardioprotective effect of EGb 761 was completely
      abolished by atractyloside.

PMID- 24914285
TI  - Germplasm preservation in vitro of Polygonum multiflorum Thunb.
AB  - BACKGROUND: The root of Polygonum multiflorum Thunb. is a common traditional
      Chinese medicine. In recent years, the wild resources of P. multiflorum have been
      seriously broken, and the cultivated varieties have been degrading. The germplasm
      resources of P. multiflorum need protection and preservation. So far, no in vitro
      germplasm preservation of P. multiflorum has been reported. OBJECTIVE: To explore
      a method for the in vitro germplasm preservation of P. multiflorum. MATERIALS AND
      METHODS: A large number of buds from seed explants were induced by tissue
      culture. The single buds were used as experimental materials to study the effects
      of plant growth regulator, temperature, and osmotic pressure on the preservation
      time, growth recovery, and genetic stability. RESULTS: When the buds were
      inoculated onto Murashige and Skoog (MS) basal media containing 4% w/v sucrose,
      2% w/v mannitol, and 1% w/v sorbitol, supplemented with paclobutrazol (PP333) 1.0
      mg/l, abscisic acid (ABA) 5.0 mg/l, and daminozide (B9) 30.0 mg/l in an
      illuminated chamber under a 16 h photoperiod of 1500 lx light intensity at 15
      degrees C for 10 months, the survival rate was over 70% with good growth recovery
      and genetic stability. CONCLUSION: The results of this study can be used for
      medium-term in vitro germplasm preservation of P. multiflorum, and meeting actual
      needs of research and production.

PMID- 24914286
TI  - Flavonols and derivatives of gallic acid from young leaves of Toona sinensis (A.
      Juss.) Roemer and evaluation of their anti-oxidant capacity by chemical methods.
AB  - BACKGROUND: Toona sinensis (A. Juss.) Roemer is an endemic species of Toona genus
      native to Asia. Its crude extract exhibits an effective anti-oxidant capacity
      against oxidative models, but the intrinsic substances responsible for this
      capacity in the extract remains unclear and is yet to be studied comprehensively.
      OBJECTIVE: To investigate the chemical constituents of the young leaves of Toona
      sinensis and its anti-oxidant capacity. MATERIALS AND METHODS: Silica gel column
      chromatography, preparative high-performance liquid chromatography (HPLC),
      nuclear magnetic resonance (NMR), and mass spectrometry (MS) were used to isolate
      and characterize the chemical constituents. Four chemical-induced oxidative
      models including DPPH free-radical scavenging assay, phenazine methosulphate
      (PMS) nicotinamide adenine dinucleotide (NADH) PMS-NADH-NBT superoxide anion
      scavenging assay, FeCl3-K3Fe (CN)6 reducing power assay, and FeCl2-FerroZine
      metal chelation assay were applied in the present study for evaluating anti
      oxidant capacity. RESULTS: Five flavonols and three derivatives of gallic acid,
      including quercetrin, kaempferol-3-O-alpha-L-rhamopyranoside, astragalin,
      quercetin, kaempferol, methyl gallate, ethyl gallate, and 1, 2, 3, 4, 6-penta-O
      galloyl-beta-D-glucopyranose were isolated from the leaves. Results showed that
      these compounds exhibited various antioxidant properties, markedly either as the
      strong scavengers for superoxide and free radicals or as molecules that were
      reducing or metal chelating in nature. CONCLUSION: The findings suggested that
      the 8 compounds in the young leaves of T. sinensis that were isolated in our
      study were the active compounds responsible for its antioxidant activity. These
      compounds can be utilized as a potential health supplement, as an available
      source of natural antioxidants, and as an effective material in pharmaceutical
      applications.

PMID- 24914287
TI  - Effect of different growth stages of Ziziphora clinopodioides Lam. on its
      chemical composition.
AB  - AIMS: The aim of this study is to monitor the changes in the chemical composition
      of Ziziphora clinopodioides Lam. throughout nine different growth stages.
      MATERIALS AND METHODS: Volatile components such as essential oils were analyzed
      using the gas chromatography (GC) and GC-mass spectrometry, and the contents of
      non-volatile components were determined by a visible spectrophotometer. RESULTS:
      Hydro-distilled essential oil content ranged from a minimum of 1.1% (in the post
      flowering stage) to a maximum of 1.8% (in the flowering stage). The essential
      oils included pulegone, which was the most abundant component (77.48-87.3%), p
      menthanone (2.79-12.39%), trans-isopulegone (1.04-2.06%), d-limonene (0.51-3.03%)
      and eucarvone (1.5-4.48%). The contents of non-volatile components, such as that
      of total phenolics (TPC), total flavonoids (TFC), total triterpenoids content
      (TTC) and total free amino acids content (TFAAC) were measured using visible
      spectrophotometry. In the growing stage, TPC, TFC, TTC and TFAAC were 9.91-12.80
      mg/g, 29.84-50.63 mg/g, 0.57-1.41 mg/g and 13.33-28.56 mg/g, respectively.
      CONCLUSION: These data can be used as a basis to determine the optimal harvest
      time of Z. clinopodioide Lam.

PMID- 24914288
TI  - Chemical analysis, antioxidant, antichemotactic and monoamine oxidase inhibition
      effects of some pteridophytes from Brazil.
AB  - BACKGROUND: Ferns are a group of plants that have been little explored from a
      chemical and biological perspective but that have interesting potential,
      occurring in various parts of the world. OBJECTIVE: This work investigates the
      chemical profile and the biological effects of ferns from Brazil. MATERIALS AND
      METHODS: Analyses were performed using rapid performance liquid chromatography
      (RP-LC) with a diode array detector (DAD). Extracts were tested for their in
      vitro antioxidant activity, by the total reactive antioxidant potential method
      and for their antichemotactic potential, by the Boyden chamber method. Cytotoxic
      effects were assessed by lactate dehydrogenase levels, while the monoamine
      oxidase (MAO) assay was carried out using a fluorescence-based method. RESULTS:
      Different chemical compositions were found for the studied ferns, such as
      Asplenium gastonis, in which hesperidin was identified in its extract, while A.
      serra showed the presence of xanthone mangiferin. The most samples with highest
      antioxidant activity were the Asplenium serra, Lastreopsis amplissima and Cyathea
      dichromatolepis extracts, at 10 MUg/mL. High antichemotactic activity was found
      for A. serra (94.06%) and Didymochlaena truncatula (93.41%), at 10 MUg/mL. The
      extracts showed no cytotoxicity at the highest concentration. Against MAO-A, D.
      truncatula (82.61%), Alsophila setosa (82.21%), Cyathea phalerata (74.07%) and C.
      delgadii (70.32%) were the most active extracts (100 MUg/mL). CONCLUSION: The
      hypothesis was considered that phenolics and triterpenes are responsible for
      these pronounced activities.

PMID- 24914289
TI  - Stereo and region-selective biosynthesis of two new dihydroartemisinic acid
      glycosides by suspension-cultured cells of Artemisia annua.
AB  - BACKGROUND: The system of plant-cultured cells is one of the optimal systems to
      investigate biosynthesis pathway and their bioactive intermediates. OBJECTIVE: To
      study the biosynthesis of dihydroartemisinic acid (1) by suspension-cultured
      cells of Artemisia annua. MATERIALS AND METHODS: Substrate (compound 1) was
      administered into the suspension-cultured cells of A. annua and co-cultured for 2
      days. The methanol extract was separated on various column chromatography methods
      and the structures of two biosynthesis products were elucidated based on the
      analysis of (1)H NMR, (13)C NMR, 2D NMR, and ESI-MS. Time-course curve was also
      established. Furthermore, in vitro antitumor activities of compounds 1-3 against
      HepG2, K562, and A549 cell lines were evaluated by MTT assay. RESULTS: Two new
      compounds were obtained, namely 3alpha-hydroxy-dihydroartemisinic acid-alpha-D
      glucopyranosyl ester (2) and 15-hydroxy-cadin-4-en-12-oic acid-beta-d
      glucopyranosyl ester (3). The results demonstrated that the cultured cells of A.
      annua possessed the abilities to stereo-selective hydroxylate and region
      selective glycosylate sesquiterpene compounds in a highly efficient manner.
      Inhibitory effects of compounds 1-3 on proliferation of HepG2, K562, and A549
      cell lines in vitro were also investigated. CONCLUSION: Two new
      dihydroartemisinic acid glycosides were obtained by stereo- and region-selective
      biosynthesis with cultured cells of A. annua.

PMID- 24914290
TI  - Comparison of pharmacokinetic behavior of two iridoid glycosides in rat plasma
      after oral administration of crude Cornus officinals and its jiuzhipin by high
      performance liquid chromatography triple quadrupole mass spectrometry combined
      with multiple reactions monitoring mode.
AB  - OBJECTIVE: The present study examined the pharmacokinetic profiles of two iridoid
      glycosides named morroniside and loganin in rat plasma after oral administration
      of crude and processed Cornus officinals. MATERIALS AND METHODS: A rapid,
      selective and specific high-performance liquid chromatography/electrospray
      ionization tandem mass spectrometry with multiple reactions monitoring mode was
      developed to simultaneously investigate the pharmacokinetic profiles of
      morroniside and loganin in rat plasma after oral administration of crude C.
      officinals and its jiuzhipin. RESULTS: The morroniside and loganin in crude and
      processed C. officinals could be simultaneously determined within 7.4 min. Linear
      calibration curves were obtained over the concentration ranges of 45.45-4800
      ng/mL for all the analytes. The intra-and inter-day precisions relative standard
      deviation was lesser than 2.84% and 4.12%, respectively. CONCLUSION: The
      pharmacokinetic parameters of two iridoid glucosides were also compared
      systematically between crude and processed C. officinals. This paper provides the
      theoretical proofs for further explaining the processing mechanism of Traditional
      Chinese Medicines.

PMID- 24914291
TI  - Characteristics and kinetics of catalpol degradation and the effect of its
      degradation products on free radical scavenging.
AB  - BACKGROUND: The dried and steamed roots of Rehmannia glutinosa have different
      pharmacological functions and indications. Catalpol, the main active component of
      the dried root, was found to be entirely degraded together with amino acids and
      some oligosaccharides during preparation of the steamed root. Its degradation may
      contribute to the differences between dried and steamed roots. OBJECTIVE: To
      reveal the characteristics and kinetics of catalpol degradation, and evaluate its
      influence on the antioxidant properties of steamed Rehmannia roots. MATERIALS AND
      METHODS: Purified catalpol was heated under different pH and temperature values
      for different times, alone or with sugars or amino acids. Catalpol concentration
      was determined by high-performance liquid chromatography. Browning was expressed
      by the absorbance at 420 nm (A420), and antioxidation was displayed by 2,2
      diphenyl-1-picrylhydrazyl free radical scavenging ability (SADPPH). Activation
      energy was calculated using Arrhenius plotting. RESULTS: Catalpol was stable in
      neutral conditions and sensitive to acidic pH under high temperatures. Sugars had
      no influence on catalpol degradation; however, most amino acids, except for
      proline, could promote the degradation, and were associated with an increase in
      A420 and SADPPH values. These changes were proved to be mainly related with
      catalpol aglycone and were dependent on the presence of amino acids. Catalpol
      degradation was found to obey first-order kinetics. The activation energies were
      81.7, 88.8 and 98.7 kJ/mol at pH 4.0, 5.0, and 6.0 respectively, and 70.7 kJ/mol
      at pH 4.0 value and in the presence of glycine. CONCLUSIONS: Catalpol
      degradation, especially, in the presence of amino acids can substantially boost
      antioxidant properties of the products; therefore, the traditional method for
      processing Rehmannia root seems rather apt.

PMID- 24914292
TI  - Composition of the essential oil of Cynanchum mongolicum (Asclepiadaceae) and
      insecticidal activities against Aphis glycines (Hemiptera: Aphidiae).
AB  - BACKGROUND: Farmers have applied Cynanchum mongolicum (Maxim) to control crop
      pests. The aim of this study was to analyze composition of essential oil from C.
      mongolicum, evaluate insecticidal activities against Aphis glycines, and lethal
      doses. MATERIALS AND METHODS: Essential oil from C. mongolicum was efficiently
      extracted by steam distillation. The main components of the oil were analyzed
      with a gas chromatography/mass spectrometry (GC/MS) system, and the insecticidal
      activity of the essential oil on soybean aphids Aphis glycines was tested using a
      variety of methods. RESULTS: The components of the essential oil from C.
      mongolicum mainly included terpenes and ester compounds, of which (Z)-3-Hexen-1
      ol acetate, cis-3-hexenyl isovalerate, alpha-farnesene, and beta-caryophyllene
      accounted for 15.8, 10.4, 8.4, and 5.5%, respectively. With 1- and 2-day
      exposure, the essential oil showed pronounced contact toxicity (median lethal
      concentration (LC50) =37.8 and 38.4 MUL/mL, respectively), weak fumigant toxicity
      (LC50 = 139.7 and 139.9 MUL/L, respectively). The essential oil showed strong
      deterrent activity on soybean aphids in 2 and 4 h. CONCLUSION: The essential oil
      of C. mongolicum contained insecticidal components and possessed contact toxicity
      and deterrent activity to A. glycines.

PMID- 24914293
TI  - Identification of sulfur fumed Pinelliae Rhizoma using an electronic nose.
AB  - BACKGROUND: Pinelliae Rhizoma is a commonly used Chinese herb which will change
      brown during the natural drying process. However, sulfur fumed Pinelliae Rhizoma
      will get a better appearance than naturally dried one. Sulfur fumed Pinelliae
      Rhizoma is potentially toxical due to sulfur dioxide and sulfites formed during
      the fuming procedures. The odor components in sulfur fumed Pinelliae Rhizoma is
      complex. At present, there is no analytical method available to determine sulfur
      fumed Pinelliae Rhizoma simply and rapidly. To ensure medication safety, it is
      highly desirable to have an effective and simple method to identify sulfur fumed
      Pinelliae Rhizoma. MATERIALS AND METHODS: This paper presents a novel approach
      using an electronic nose based on metal oxide sensors to identify whether
      Pinelliae Rhizoma was fumed with sulfur, and to predict the fuming degree of
      Pinelliae Rhizoma. Multivariate statistical methods such as principal components
      analysis (PCA), discriminant factorial analysis (DFA) and partial least squares
      (PLS) were used for data analyzing and identification. The use of the electronic
      nose to discriminate between different fuming degrees Pinelliae Rhizoma and
      naturally dried Pinelliae Rhizoma was demonstrated. RESULTS: The electronic nose
      was also successfully applied to identify unknown samples including sulfur fumed
      samples and naturally dried samples, high recognition value was obtained.
      Quantitative analysis of fuming degree of Pinelliae Rhizoma was also
      demonstrated. The method developed is simple and fast, which provides a new
      quality control method of Chinese herbs from the aspect of odor. CONCLUSION: It
      has shown that this electronic nose based metal oxide sensor is sensitive to
      sulfur and sulfides. We suggest that it can serve as a supportive method to
      detect residual sulfur and sulfides.

PMID- 24914294
TI  - An enzoinformatics study targeting polo-like kinases-1 enzyme: Comparative
      assessment of anticancer potential of compounds isolated from leaves of Ageratum
      houstonianum.
AB  - Natural products from plant sources, embracing inherently ample structural
      diversity than synthetic ones are the major sources of anticancer agents and will
      constantly play as protagonists for discovering new drugs. Polo-like kinases
      (PLKs) play a leading role in the ordered execution of mitotic events and 4
      mammalian PLK family members have been identified. PLK1 is an attractive target
      for anticancer drugs in mammalian cells, among the four members of PLKs. The
      present study expresses the molecular interaction of compounds (1,2
      Benzenedicarboxylic acid bis (2 ethylhexyl) ester, squalene, 3,5-bis (1,1
      dimethylethyl) phenol, Pentamethyl tetrahydro-5H-chromene, (1,4-Cyclohexylphenyl)
      ethanone and 6-Vinyl-7-methoxy-2,2-dimethylchromene) isolated from methanolic
      extract of leaves of Ageratum houstonianum with PLK1 enzyme. Docking between PLK1
      and each of these compounds (separately) was performed using "Auto dock 4.2."
      (1,4-Cyclohexylphenyl) ethanone showed the maximum potential as a promising
      inhibitor of PLK1 enzyme with reference to ?G (-6.84 kcal/mol) and Ki (9.77 MUM)
      values. This was sequentially followed by Pentamethyl tetrahydro-5H-chromene (?G
      = -6.60 kcal/mol; Ki = 14.58 MUM), squalene (?G = -6.17 kcal/mol; Ki = 30.12
      MUM), 6-Vinyl-7-methoxy-2,2-dimethylchromene (?G = -5.91 kcal/mol; Ki = 46.68
      MUM), 3, 5-bis (1,1-dimethylethyl) phenol (?G = -5.70 kcal/mol; Ki = 66.68 MUM)
      and 1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester (?G = -5.58 kcal/mol;
      Ki = 80.80 MUM). These results suggest that (1,4-Cyclohexylphenyl) ethanone might
      be a potent PLK1 inhibitor. Further, in vitro and in vivo rumination are
      warranted to validate the anticancer potential of (1,4-Cyclohexylphenyl)
      ethanone. 

PMID- 24914295
TI  - Ultrasound-assisted extraction of total flavonoids from Aconitum gymnandrum.
AB  - BACKGROUND: Aconitum gymnandrum is a Chinese traditional herb used as carminative
      and analgesic. In this study, A. gymnandrum was used as an experimental matrix.
      MATERIALS AND METHODS: Optimized ultrasonic extraction technology of total
      flavonoids from the A. gymnandrum Maxim was studied by using the methodology of
      single factor and orthogonal design to study the effects of operation conditions,
      such as ethanol content, ultrasonic wave power, temperature, ultrasonic wave
      radiation time, and the ratio of sample weight to solvent volume. RESULT: THROUGH
      THE ORTHOGONAL EXPERIMENT, THE OPTIMAL EXTRACTION CONDITIONS WERE DETERMINED AS
      FOLLOWS: Ultrasonic power 100 W, ultrasonic temperature 45 degrees C, 60% ethyl
      alcohol, extraction time 30 min, and solid-liquid ratio 1:20. CONCLUSION: Under
      the optimum parameters, the extraction ratio of total flavonoids from the A.
      gymnandrum Maxim is about 1.278%.

PMID- 24914296
TI  - Protective effects of Aegle marmelos fruit pulp on 2,4,6-trinitrobenzene sulfonic
      acid-induced experimental colitis.
AB  - BACKGROUND: Aegle marmelos (AM) fruit has been advocated in indigenous system of
      medicine for the treatment of various gastrointestinal disorders, fever, asthma,
      inflammations, febrile delirium, acute bronchitis, snakebite, epilepsy, leprosy,
      myalgia, smallpox, leucoderma, mental illnesses, sores, swelling, thirst, thyroid
      disorders, tumours and upper respiratory tract infections. OBJECTIVE: The
      objective of this study was to study the curative effect of 50% ethanol extract
      of dried fruit pulp of AM (AME) against 2,4,6-trinitrobenzene sulfonic acid
      (TNBS)-induced experimental colitis. MATERIALS AND METHODS: AME (200 mg/kg) was
      administered orally, once daily for 14 days after TNBS-induced colitis. Rats were
      given intracolonic normal saline or TNBS alone or TNBS plus oral AME. AME was
      studied for its in vitro antibacterial activity against Gram-negative intestinal
      bacteria and on TNBS-induced changes in colonic damage, weight and adhesions
      (macroscopic and microscopic), diarrhea, body weight and colonic levels of free
      radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide
      dismutase, catalase and reduced glutathione) and pro-inflammatory marker
      (myeloperoxidase [MPO]) in rats. RESULTS: AME showed antibacterial activity
      against intestinal pathogens and decreased colonic mucosal damage and
      inflammation, diarrhea, colonic free radicals and MPO and enhanced body weight
      and colonic antioxidants level affected by TNBS. The effects of AME on the above
      parameters were comparable with sulfasalazine, a known colitis protective drug
      (100 mg/kg, oral). CONCLUSION: AME shows curative effects against TNBS-induced
      colitis by its antibacterial activity and promoting colonic antioxidants and
      reducing free radicals and MPO-induced colonic damage.

PMID- 24914297
TI  - Dichlorodiaportinol A - A new chlorine-containing isocoumarin from an endophytic
      fungus Trichoderma sp. 09 from Myoporum bontioides A. Gray and its cytotoxic
      activity.
AB  - BACKGROUND: Myoporum bontioides A. Gray, an evergreen shrub from the Myoporaceae
      family, is a commonly used medicinal plant. Many studies have been conducted on
      the biologically active constituents of whole parts of M. bontioides. However,
      the endophytes of M. bontioides have not been intensively investigated. A new
      chlorine-containing isocoumarin, named dichlorodiaportinol A (1) was isolated
      from the endophytic fungus Trichoderma sp. 09 isolated from the root of M.
      bontioides. Its cytotoxic activity against human breast cancer (MCF-7) and human
      liver cancer (HepG2) cell lines was evaluated. MATERIALS AND METHODS: Different
      open silica gel column chromatographic techniques with different solvent systems
      were used for the separation of the constituents of the ethyl acetate extract of
      the culture broth of the endophytic fungus Trichoderma sp. 09. The structure of
      compound one was identified by analysis of spectroscopic data [one-dimensional
      (1D), two-dimensional (2D)-nuclear magnetic resonance (NMR), ultraviolet (UV),
      infrared (IR) and Mass spectrometry (MS)]. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      Diphenyltetrazolium Bromide (MTT) assay method was used for the evaluation of
      cytotoxic activity of compound one against MCF-7 and HepG2 cell lines. RESULTS:
      Compound one was identified as 3-(3,3-dichloro-2,3-dihydroxy-propyl)-8-hydroxy-6-
      methoxy-isochromen-1-one. It inhibited MCF-7 and HepG2 cell lines, with half
      maximal inhibitory concentration (IC50) values of 17.8 and 39.6 MUg/mL,
      respectively. CONCLUSIONS: Compound one is a new chlorine-containing isocoumarin
      with moderate cytotoxic activity against MCF-7 and HepG2 cell lines. Thus,
      endophytes of M. bontioides are worthy of consideration for the development and
      research of antitumor agents.

PMID- 24914298
TI  - In vitro anti-telomerase activity of novel lycopene-loaded nanospheres in the
      human leukemia cell line K562.
AB  - BACKGROUND: Lycopene, a plant carotenoid, has potent effects against the various
      types of cancer cells. To date, the effect of lycopene in the free and
      encapsulated forms on the telomerase activity in human leukemia cell line K562
      have not been investigated. The aim of the present study was to prepare a novel
      lycopene-loaded nanosphere and compare its anti-telomearse activity in K562 cell
      line with those of free lycopene. MATERIALS AND METHODS: The lycopene-loaded
      nanospheres were prepared by nanoprecipitation method. The lycopene entrapment
      efficacy was measured by high-performance liquid chromatography (HPLC) method.
      The anti-proliferation effect of the lycopene in the free and encapsulated forms
      in the different times (0-72 h) and the different doses (0-100 MUg/ml) on K562
      cell line was studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay. The changes of telomerase activity, following
      treatment with the lycopene in the free and encapsulated forms, were detected
      using the telomeric repeat amplification protocol-enzyme-linked immunosorbent
      assay. RESULTS: The entrapment efficacy of lycopene was 78.5% +/- 2. Treatment of
      the K562 cell line with lycopene, in particular in encapsulated form, resulted in
      a significant inhibition of the cell growth and increasing of percentage of
      apoptotic cells. It has also been observed that the telomerase activity in the
      lycopene-loaded nanospheres-treated cells was significantly inhibited in a dose
      and time-dependent manner. CONCLUSION: Our data suggest a novel mechanism in the
      anti-cancer activity of the lycopene, in particular in encapsulated form, and
      could be provided a basis for the future development of anti-telomerase
      therapies.

PMID- 24914299
TI  - Chemical composition of the volatile oil from Zanthoxylum avicennae and
      antimicrobial activities and cytotoxicity.
AB  - BACKGROUND: Through literature retrieval, there has been no report on the
      research of the chemical components in Zanthoxylum avicennae (Lam.) DC. This
      paper extracted and determined the chemical components of the volatile oil in Z.
      avicennae, and at the same time, measured and evaluated the bioactivity of the
      volatile oil in Z. avicennae. MATERIALS AND METHODS: We extract the volatile oil
      in Z. avicennae by steam distillation method, determined the chemical composition
      of the volatile oil by GC-MS coupling technique, and adopt the peak area
      normalization method to measured the relative percentage of each chemical
      composition in the volatile oil. Meanwhile, we use the Lethal-to-prawn larva
      bioactivity experiment to screen the cytotoxicity activities of the volatile oil
      in Z. avicennae, and using the slanting test-tube experiment to determine and
      evaluate its antibacterial activities in vitro for the eight kinds of plant
      pathogenic fungi in the volatile oil of the Z. avicennae. RESULTS: The results
      show that 68 kinds of compounds are determined from the volatile oil of Z.
      avicennae. The determined part takes up 97.89% of the total peak area. The main
      ingredients in the volatile oil of Z. avicennae are sesquiterpenoids and
      monoterpene. The test results show that the volatile oil in Z. avicennae has
      strong antibacterial activities and cytotoxicity, with the strongest
      antibacterial activity against the Rhizoctonia solani AG1-1A. CONCLUSION: This
      research results will provide reference data for understanding the chemical
      composition of the volatile oil in the aromatic plant of Z. avicennae and its
      bioactivity, and for its further development and application.

PMID- 24914300
TI  - Increased acetylcholine esterase activity produced by the administration of an
      aqueous extract of the seed kernel of Thevetia peruviana and its role on acute
      and subchronic intoxication in mice.
AB  - BACKGROUND: The real mechanism for Thevetia peruviana poisoning remains unclear.
      Cholinergic activity is important for cardiac function regulation, however, the
      effect of T. peruviana on cholinergic activity is not well-known. OBJECTIVE: To
      study the effect of the acute administration of an aqueous extract of the seed
      kernel of T. peruviana on the acetylcholine esterase (AChE) activity in CD1 mice
      as well its implications in the sub-chronic toxicity of the extract. MATERIALS
      AND METHODS: A dose of 100 mg/kg of the extract was administered to CD1 mice and
      after 7 days, serum was obtained for ceruloplasmin (CP) quantitation and liver
      function tests. Another group of mice received a 50 mg/kg dose of the extract 3
      times within 1 h time interval and AChE activity was determined for those
      animals. Heart tissue histological preparation was obtained from a group of mice
      that received a daily 50 mg/kg dose of the extract by a 30-days period. RESULTS:
      CP levels for the treated group were higher than those for the control group
      (Student's t-test, P <= 0.001). AChE activity in the treated group was
      significantly higher than the control group (Tukey test, control vs. T.
      peruviana, P <= 0.001). Heart tissue histological preparations showed leukocyte
      infiltrates and necrotic areas, consistent with infarcts. CONCLUSION: The
      increased levels of AChE and the hearth tissue infiltrative lesions induced by
      the aqueous seed kernel extract of T. peruviana explains in part the poisoning
      caused by this plant, which can be related to an inflammatory process.

PMID- 24914301
TI  - Optimization of genetic transformation of Artemisia annua L. Using Agrobacterium
      for Artemisinin production.
AB  - BACKGROUND: Artemisinin, a sesquiterpene lactone endoperoxide isolated from the
      medicinal plant Artemisia annua L., is a choice and effective drug for malaria
      treatment. Due to the low yield of artemisinin in plants, there is a need to
      enhance the production of artemisinin from A. annua and biotechnological
      technique may be one of the methods that can be used for the purpose. AIM: To
      study the transformation efficiency of Agrobacterium tumefaciens in A. annua that
      could be applied to enhance the production of artemisinin by means of transgenic
      plants. SETTING AND DESIGNS: The factors influencing Agrobacterium-mediated
      transformation of A. annua were explored to optimize the transformation system,
      which included A. tumefaciens strain and effect of organosilicone surfactants.
      Three strains of A. tumefaciens, that is, LBA4404, GV1301, and AGL1 harboring the
      binary vector pCAMBIA 1303 have been used for transformation. The evaluation was
      based on transient beta-glucuronidase (GUS). MATERIALS AND METHODS: Plant cell
      cultures were inniatiated from the seeds of A. annua using the germination
      Murashige and Skoog medium. A. tumefaciens harboring pCAMBIA were tranformed into
      the leaves of A.annua cultures from 2-week-old-seedling and 2-month-old-seedling
      for 15 min by vacuum infiltration. Transformation efficiency was determinated by
      measuring of blue area (GUS expression) on the whole leaves explant using ImageJ
      1.43 software. Two organosilicon surfactants, that is, Silwet L-77 and Silwet S
      408 were used to improve the transformation efficiency. RESULTS: The
      transformation frequency with AGL1 strain was higher than GV3101 and LBA4404
      which were 70.91, 49.25, and 45.45%, respectively. Effect of organosilicone
      surfactants, that is, Silwet L-77 and Silwet S-408 were tested on A. tumefaciens
      AGL1 and GV3101 for their level of transient expression, and on A. rhizogenes
      R1000 for its hairy root induction frequency. For AGL1, Silwet S-408 produced
      higher level of expression than Silwet L-77, were 2.3- and 1.3-fold,
      respectively. For GV3101, Silwet L-77 was still higher than Silwet S-408, were
      1.5- and 1.4-fold, respectively. However, GV3101 produced higher levels of
      expression than AGL1. The area of GUS expression spots of AGL1, LBA4404, and
      GV3101 strains was 53.43%, 41.06%, and 30.51%, respectively. CONCLUSION: A.
      tumefaciens AGl1 strain was the most effective to be transformed in to A. annua
      than GV3101 and LBA4404 strain. Surfactant Silwet S-408 produced the highest
      efficiency of transformation.

PMID- 24914302
TI  - Source of variation of isoflavone concentrations in perennial clover species.
AB  - INTRODUCTION: Clover has attracted considerable interest not only as a valuable
      livestock forage plant, but also as an important source of isoflavones. The
      current study was aimed to assess the variation of concentration of three
      isoflavones in clover species grown under a cool temperate climate environment in
      Lithuania. MATERIALS AND METHODS: Isoflavone contents were quantified in the
      plant parts of 21 accessions belonging to five perennial species of genus
      Trifolium (T. pratense, T. repens, T. medium, T. rubens, and T. pannonicum).
      Daidzein, formononetin, and genistein concentrations were quantified in separate
      plant parts by reversed-phase high-performance liquid chromatography. The analyte
      extraction was performed from dried and ground leaves, stems, flowers, and roots.
      The procedure included acid hydrolysis of isoflavone glycosides to aglycones.
      RESULTS: According to the averaged sum of the three isoflavones quantified in
      leaves-stems-flowers, the five clover species ranked as follows: T. medium (7.54
      3.62-2.31 mg/g) >T. pratense> T. rubens> T. pannonicum> T. repens (0.191-0.204
      0.171 mg/g). The contribution of individual compound to the total isoflavone
      content depended on the species, accession, and plant part. The major part of the
      isoflavones is concentrated in leaves or stems; however, there is a great
      variation also. CONCLUSION: There exists a large variation in the total as well
      as in individual concentration of isoflavones among the clover species and plant
      parts and within species. With regard to isoflavone concentration and variability
      within species, some accessions of T. medium and T. pratense can be considered a
      highly promising source of phytoestrogens.

PMID- 24914303
TI  - Multi-component analysis in sun-dried and sulfur-fumigated Angelicae Sinensis
      Radix by single marker quantitation and chemometric discrimination.
AB  - BACKGROUND: A new method has been developed for the simultaneous determination of
      ferulic acid, senkyunolide A, and Z-ligustilide in Angelicae Sinensis Radix
      before and after sulfur-fumigation using quantitative analysis of multi
      components by a single marker (QAMS). MATERIALS AND METHODS: The feasibility and
      accuracy of QAMS were checked by the external standard method, and various high
      performance liquid chromatographic instruments and chromatographic conditions
      were investigated to verify its applicability. Using ferulic acid as the internal
      reference substance, and the contents of senkyunolide A and Z-ligustilide were
      calculated according to relative correction factors by high-performance liquid
      chromatography. Meanwhile, the influence of sulfur-fumigation on these chemical
      components in Angelicae Sinensis Radix were evaluated and discriminated by
      chromatographic fingerprint and chemometrics. RESULTS: There was no significant
      difference observed between the QAMS method and the external standard method.
      Furthermore, sulfur-fumigation reduced the contents of ferulic acid, senkyunolide
      A, and Z-ligustilide in Angelicae Sinensis Radix by some degree, and the sun
      drying and sulfur-fumigation processing could be easily discriminated by
      chromatographic fingerprint and chemometrics. CONCLUSION: QAMS is a convenient
      and accurate approach to analyzing multi-component when reference substances are
      unavailable, simultaneously, chemometrics is an effective way to discriminate sun
      dried and sulfur-fumigated Angelicae Sinensis Radix.

PMID- 24914304
TI  - Rapid, sensitive, and validated UPLC/Q-TOF-MS method for quantitative
      determination of vasicine in Adhatoda vasica and its in vitro culture.
AB  - BACKGROUND: Adhatoda vasica a perennial herb has been used in Ayurvedic and Unani
      system of medicines since last 2000 years and has been employed for the treatment
      of respiratory tract ailments. OBJECTIVE: To develop and validate new, rapid, and
      highly sensitive high throughput ultra-performance liquid
      chromatography/quadrupole-time-of-flight mass-spectrometry (UPLC/Q-TOF-MS) method
      for the quantitative estimation of vasicine in the leaves and to establish in
      vitro cultures of Adhatoda vasica for production of vasicine. MATERIALS AND
      METHODS: The chromatographic separation was achieved on a Waters ACQUITY UPLCTM
      BEH C8 (100.0 * 2.1 mm; 1.7 MUm) column packing using isocratic mobile phase
      consisting of acetonitrile: 20 mM ammonium acetate (90:10; v/v) in a multiple
      reactions monitoring mode using the transitions m/z 189.09 -> 171.08 for
      vasicine. RESULTS: The vasicine was eluted at 2.58 +/- 0.05 min and established a
      dynamic range of linearity over the concentration range of 1-1000 ng/ml (r (2) =
      0.999 +/- 0.0005). The lower limit of detection and quantification was 0.68 and
      1.0 ng/ml, respectively. There was no significant difference observed in the
      content of vasicine (0.92-1.04%w/w) among the eleven samples collected from
      different locations of India. The in vitro cultures developed showed that
      addition of extra 28 mM KNO3 and 100 mM NaCl in MS medium supplemented with 2,4
      dichlorophenoxyacetic acid (2,4-D) + benzyladenine (BA) + indole acetic acid
      (IAA) (1 ppm each) produces faster biomass and higher amount of quinazoline
      alkaloids. CONCLUSION: Rapid, efficient, and sensitive UPLC/Q-TOF-MS method was
      developed for the estimation of vasicine and an efficient protocol for
      development of in vitro cultures was proposed, which can be used at large scale
      for industrial production of vasicine using bioreactors.

PMID- 24914305
TI  - Simultaneous determination of five major compounds in the traditional medicine
      Pyeongwee-San by high performance liquid chromatography-diode array detection and
      liquid chromatography-mass spectrometry/mass spectrometry.
AB  - BACKGROUND: Pyeongwee-San (PWS) has been widely used for treating acute
      gastritis, chronic, and gastritis. OBJECTIVE: In this paper, simultaneous
      determination of five compounds (naringin, hesperidin, glycyrrhizin,
      atractylenolide III, and magnolol) from traditional medicine PWS using the high
      performance liquid chromatography (HPLC) was established for quality control.
      MATERIALS AND METHODS: Optimum separations were obtained with a SHISEIDO C18
      reverse-phase column by gradient elution with 0.1% Trifluoroacetic acid (TFA)
      water-acetonitrile as the mobile phase. The flow rate was 1 mL/min and detection
      wavelength was set at 205 nm and 250 nm. Validation of the analytical method was
      evaluated by linearity, precision, and accuracy test. RESULTS: The calibration
      curves were linear over the established range with R (2) > 0.9978. The limit of
      detection (LOD) and limit of quantification (LOQ) ranged from 0.09 to 0.43 and
      0.27 to 1.29 MUg/mL. The method exhibited intra-day and inter-day precision range
      between 0.01-1.86% and 0.04-0.35% respectively. The recoveries of five compounds
      in PWS were in the range between 93.18-106.40%, and 0.20-1.51%. The application
      of this method was identified through the successful analysis of five compounds
      in 12 batches of PWS. In addition, identification of five compounds was confirmed
      by a liquid chromatography method and mass spectrometry. CONCLUSION: The HPLC
      method was could be accomplished to the quality control and stable experiment for
      the preparations consisted of five major compounds.

PMID- 24914306
TI  - Element analysis and characteristic identification of non-fumigated and sulfur
      fumigated Fritillaria thunbergii Miq. using microwave digestion-inductively
      coupled plasma atomic emission spectrometry combined with Fourier transform
      infrared spectrometry.
AB  - BACKGROUND: Sulfur-fumigation may induce chemical transformation of traditional
      Chinese medicines leading to harmful effects following patient ingestion. For
      quality control, it is urgently needed to develop a reliable and efficient method
      for sulfur-fumigation identification. MATERIALS AND METHODS: The spectrochemical
      identification of non-fumigated and sulfur-fumigated Fritillaria thunbergii Miq.
      was carried out to evaluate inorganic elements and organic components. The
      concentrations of 12 elements, including Zn, Mn, Cu, Fe, Li, Mg, Sr, Pb, As, Cd,
      Hg, and S of samples were determined by microwave digestion - inductively coupled
      plasma atomic emission spectrometry (ICP-AES). Meanwhile, Fourier transform
      infrared spectrometry (FTIR) was used for the study of chemical group
      characteristic reactions after sulfur-fumigation. RESULTS: The concentrations of
      Fe, Mg, Hg, and S elements showed significant differences between non-fumigated
      and sulfur-fumigated Fritillaria thunbergii Miq. The characteristic stretching
      vibrations of some groups in FTIR spectra, such as -OH, -S = O and -S-O, provided
      the identification basis for the discrimination of non-fumigated and sulfur
      fumigated Fritillaria thunbergii Miq. CONCLUSION: The application of microwave
      digestion - ICP-AES was successfully used in combination with FTIR to
      authenticate and evaluate the quality of medicinal Fritillaria thunbergii Miq.
      Further applications of this technique should be explored.

PMID- 24914307
TI  - Gas chromatography-mass spectroscopy analysis of bioactive petalostigma extracts:
      Toxicity, antibacterial and antiviral activities.
AB  - BACKGROUND: Petalostigma pubescens and Petalostigma triloculare were common
      components of pharmacopeia's of multiple Australian Aboriginal tribal groupings
      which traditionally inhabited the areas in which they grow. Among these groups,
      they had a myriad of medicinal uses in treating a wide variety of bacterial,
      fungal and viral infections. This study was undertaken to test P. pubescens and
      P. triloculare leaf and fruit extracts for the ability to inhibit bacterial and
      viral growth and thus validate Australian Aboriginal usage of these plants in
      treating bacterial and fungal diseases. MATERIALS AND METHODS: P. pubescens, and
      P. triloculare leaves and fruit were extracted and tested for antimicrobial,
      antiviral activity and toxicity. The bioactive extracts were further examined by
      RP-HPLC and GC-MS to identify the component compounds. RESULTS: The methanol,
      water and ethyl acetate leaf and fruit extracts of displayed potent antibacterial
      activity. The methanol and ethyl acetate extracts displayed the broadest
      specificity, inhibiting the growth of 10 of the 14 bacteria tested (71%) for the
      leaf extract and 9 of the 14 bacteria tested (64%) for the fruit extracts. The
      water extracts also had broad spectrum antibacterial activity, inhibiting the
      growth of 8 (57%) and 7 (50%) of the 14 bacteria tested, respectively. All
      antibacterial extracts were approximately equally effective against Gram-positive
      and Gram-negative bacteria, inhibiting the growth of 50-75% of the bacteria
      tested. The methanol, water and ethyl acetate extracts also displayed antiviral
      activity in the MS2 plaque reduction assay. The methanol and water extracts
      inhibited 26.6-49.0% and 85.4-97.2% of MS2 plaque formation, respectively, with
      the fruit extracts being more potent inhibitors. All ethyl acetate extracts
      inhibited 100% of MS2 plaque formation. All extracts were also non-toxic or of
      low toxicity. Analysis of these extracts by RP-HPLC showed that the P.
      triloculare ethyl acetate fruit extract was the least complex of the bioactive
      extracts. Subsequent analysis of this extract by GC-MS revealed that it contained
      9 main compounds: acetic acid; 2,2-dimethoxybutane; 4-methyl-1,3-dioxane; decane;
      unadecane; 2-furanmethanol; 1,2-benzenediol; 1,2,3-benzenetriol; and benzoic
      acid. CONCLUSION: These studies validate Australian Aboriginal therapeutic usage
      of Petalostigma species and indicate their medicinal potential.

PMID- 24914308
TI  - Antidepressant-like activity of Chaihu-Shugan-San aqueous extract in rats and its
      possible mechanism.
AB  - BACKGROUND: Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal formula,
      is commonly used for the treatment of depression in China. However, the molecular
      mechanism underlying its antidepressant action is unknown. OBJECTIVE: The
      objective of this study is to evaluate the antidepressant-like effects of CHSGS
      and further explore the possible molecular mechanism implicated in its actions.
      MATERIALS AND METHODS: THE RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS: The
      normal control group, the model control group, the CHSGS group and the fluoxetine
      control group. The antidepressant-like effects of CHSGS aqueous extract were
      assessed in rats exposed to chronic mild stress (CMS) using the open-field test
      and sucrose water consumption test, its underlying mechanism of anti-depression
      was explored by determining the effect of CHSGS on the extracellular signal
      regulated kinase (ERK) and phospho-ERK (P-ERK) in the hippocampus using western
      blot. The aqueous extract of CHSGS at a dose of standard (5.9 g/kg.d) was
      administered intragastrically for 14 days during the CMS model while the
      fluoxetine control group was given at the same time using fluoxetine
      hydrochloride (1.8 mg/kg.d). RESULTS: The stressed rats demonstrated decreased
      locomotor activity in open field test and reduction in sucrose consumption and
      decreased levels of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in the
      hippocampus. CHSGS alleviated the depressive-like behaviors and increased levels
      of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in stressed rats as well as
      fluoxetine. CONCLUSION: In summary, these results suggest that CHSGS aqueous
      extract possesses an antidepressant-like activity in CMS induced depression model
      rats, which might be mediated, at least in part, by reversing the stress-induced
      disruption of ERK activity.

PMID- 24914309
TI  - Optimization of quercitrin and total flavonoids extraction from Herba Polygoni
      Capitati by response surface methodology.
AB  - OBJECTIVE: To optimize the conditions for extraction of quercitrin and total
      flavonoids (TF) from Herba Polygoni Capitati (Touhualiao in Chinese) by using
      response surface methodology (RSM). MATERIALS AND METHODS: A central composite
      design (CCD) was adopted to investigate the effects of three independent
      variables including solvent composition (%), solvent-material ratio (ml/g) and
      extraction time (min) on the responses, quercitrin and TF yields. RESULTS: THE
      OPTIMIZED CONDITIONS OF THE EXTRACTION ARE AS FOLLOWS: Ethanol concentration,
      65.63%; solvent-material ratio, 10.55:1 (ml/g); extraction time, 54.33 min. The
      established mathematical model described the factors of experimental parameters
      well and provided a statistically accurate prediction of the optimum yields of
      quercitrin and TF. CONCLUSION: The experimental values agreed with those
      predicted by the established mathematical model, thus indicating the suitability
      of the model employed and the success of RSM in optimizing the extraction
      conditions.

PMID- 24914310
TI  - Antimicrobial, antibiofilm and cytotoxic activities of Hakea sericea Schrader
      extracts.
AB  - BACKGROUND: Hakea sericea Schrader is an invasive shrub in Portuguese forests.
      OBJECTIVE: The goal of this work was to evaluate the antimicrobial activity of H.
      sericea extracts against several strains of microorganisms, including the ability
      to inhibit the formation of biofilms. Additionally the cytotoxic properties of
      these extracts, against human cells, were assessed. MATERIALS AND METHODS: The
      antimicrobial activity of the methanolic extracts of H. sericea was assessed by
      disk diffusion assay and Minimum Inhibitory Concentration (MIC) value
      determination. The antibiofilm activity was determined by quantification of total
      biofilm biomass with crystal violet. Cytotoxicity was evaluated by hemolysis
      assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      test. RESULTS: For Gram-positive bacteria, MIC values of H. sericea methanolic
      extracts ranged between 0.040 and 0.625 mg/mL, whereas the fruits extract yielded
      the lowest MIC for several strains of microorganisms, namely, S. aureus, B.
      cereus, L. monocytogenes and clinical methicillin-resistant S. aureus (MRSA).
      Stems and fruits extract at 2.5 mg/mL effectively eradicated the biofilm of S.
      aureus ATCC 25923, SA 01/10 and MRSA 12/10. Regarding leaves extract, hemolysis
      was not observed, and in the case of stems and fruits, hemolysis was verified
      only for higher concentrations, suggesting its low toxicity. Fruits extract
      presented no toxic effect to normal human dermal fibroblasts (NHDF) cells however
      for concentrations of 0.017 and 0.008 mg/mL this extract was able to decrease
      human breast adenocarcinoma cells (MCF-7) viability in about 60%, as MTT test
      results had confirmed. This is a clearly demonstrator of the cytotoxicity of this
      extract against MCF-7 cells.

PMID- 24914311
TI  - In vitro and in silico studies on the anticancer and apoptosis-inducing
      activities of the sterols identified from the soft coral, subergorgia reticulata.
AB  - BACKGROUND: Gorgonians and other octocorals are known to possess a huge array of
      secondary metabolites in which sterols are the major group of secondary
      metabolites apart from sesquiterpenes and diterpenes, and the bioactive
      metabolites could show marked biomedical potential for future drug discovery.
      OBJECTIVE: This study was intended for the isolation and identification of
      sterols from the octocoral Subergorgia reticulata and to evaluate the anticancer
      and apoptosis-inducing activities of the identified sterols through in vitro and
      in silico approach. MATERIALS AND METHODS: The organism was collected from
      Lakshadweep Island. The isolated sterols were identified using Gas chromatography
      mass spectrometry (GC-MS). The structure was confirmed by using comparison of
      their spectra those in National Institute of Standard Technology (NIST) library.
      The apoptosis inducing effect of identified sterols were determined by PASS
      online prediction. In vitro cytotoxity studies were carried out using Dalton's
      lymphoma ascites cells (DLA) and the cell viability was determined by trypan blue
      exclusion method. RESULTS: Six sterols were identified from the soft coral S.
      reticulata. They are Cholesta-5,22-diene-3ol (3beta), Ergosta-5-22-dien-3ol
      (3beta,22E 24S), Cholesterol, 26,26-Dimethyl-5,24(28)-ergostadien-3beta-ol. beta
      sitosterol, and Fucosterol. In silico predictions showed that the identified
      sterols exhibited remarkable apoptosis agonist activity. The probability of
      apoptosis agonist activity were found maximum for 26,26-Dimethyl-5,24 (28)-S.
      reticulata sterol fractions isolated were found to be having anticancer activity.
      CONCLUSIONS: These findings suggest that S. reticulata contained biologically
      active sterol compounds that may be useful in the treatment of cancer.

PMID- 24914312
TI  - Simultaneous quantification of nine major active components in traditional
      Chinese prescription Mahuang decoction and the influence of herbal compatibility
      on their contents.
AB  - BACKGROUND: Mahuang decoction (MHD), a famous classic traditional Chinese
      formula, has been extensively applied for treating cold, influenza, asthma, acute
      bronchitis, and other pulmonary diseases. However, the interaction among four
      drugs of MHD has not been clearly deciphered from the aspect of molecular
      composition. OBJECTIVE: To assess the quality of MHD and explore the interplay
      among different prescription drugs. MATERIALS AND METHODS: A reversed-phase high
      performance liquid chromatography (RP-HPLC) coupled with diode array detector
      (DAD) method for the simultaneous separation and determination of nine bioactive
      components was developed. A somatomedin A (SMA)-phenyl column (4.6 mm * 250 mm, 5
      MUm) was eluted by a gradient mobile phase contained acetonitrile and 0.05%
      formic acid-0.05% triethylamine aqueous solution. Four detection wavelengths
      (210, 252, 278, and 291 nm) were utilized for the quantitative analysis due to
      the different ultraviolet (UV) spectra of these compounds. RESULTS: Satisfactory
      separation was obtained for all the components, and the assay was fully validated
      in respects of linearity, precision, stability, and accuracy. It was found that
      the calibration curves for all analytes showed good linearity (R (2)>= 0.9991)
      within the test ranges. The relative standard deviations (RSDs) for intra- and
      interday repeatability were not more than 1.70 and 2.66%, respectively. The spike
      recoveries of nine components varied from 97.50 +/- 1.69 to 99.27 +/- 1.37%.
      CONCLUSION: The established method was successfully applied to analyze nine
      active compounds in decoction samples of various drug compatibilities of MHD. The
      variations of contents were obvious for different combinations, which hinted the
      mutual promotion or inhibition of componential dissolution among four herbs of
      MHD.

PMID- 24914313
TI  - Antiasthmatic effects of schizandrae fructus extract in mice with asthma.
AB  - BACKGROUND: Schizandrae fructus (SF), the fruit of Schisandra chinensis, has been
      used for the treatment of cough, wheezing, dry mouth, hepatitis, cardiovascular
      disease, and as a tonic and astringent in China, Japan, and Korea. OBJECTIVE:
      Investigation of the antiasthmatic effects of SF. MATERIALS AND METHODS: We
      investigated the effects of SF on airway hyperresponsiveness (AHR) to
      methacholine, production levels of antigen-specific antibodies, and
      histopathological changes in the lung tissue in a mouse model (Balb/c) of asthma
      induced by repeated intranasal instillation of an antigen. RESULTS: SF lowered
      AHR to methacholine (P < 0.05), antigen-specific immunoglobulin E (IgE) level (P
      < 0.01), and immune cell infiltration in mice with asthma. Prednisolone (PD)
      effectively decreased AHR (P < 0.01), total antibody (P < 0.01) and IgE (P <
      0.01) levels, and immune cell infiltration. SF and PD did not affect the levels
      of antigen-specific IgG1 and IgG2a antibodies. CONCLUSION: Our data suggest that
      SF has possible application as an antiasthmatic drug. We also suggest that SF
      could be used as a complementary or alternative medicine to glucocorticoids.

PMID- 24914314
TI  - Assessment of potency of PC-complexed Ocimum sanctum methanol extract in
      embryonated eggs against Influenza virus (H1N1).
AB  - BACKGROUND: Despite of new vaccines, the threat of influenza infection persists.
      In addition, availability, cost, duration of protection rendered and
      effectiveness of vaccines additional to the need of effective drug therapy makes
      influenza a challenge, which the globe faces. Traditionally used herbs and their
      decoctions are used for ages to cure symptoms similar to influenza. Tulsi or
      Ocimum sanctum is one of these major herbs used for influenza-like disease
      treatment. We attempted to explore a new methodology for assessing phosphatidyl
      choline (PC)-complexed O. sanctum methanol extract in embryonated vaccine quality
      eggs model. MATERIALS AND METHODS: The PC-complexed O. sanctum methanol extract
      was prepared and standardized using High-Performance Liquid Chromatography
      (HPLC). (Data not provided here) Nine to 11 days embryonated eggs were inoculated
      with the virus and drug mixture and then harvested to perform a hemagglutination
      (HA) test on the allantoic fluid. The experiments were performed at three
      different concentrations of ursolic acid with various virus concentration and
      dose levels of drugs. The HA titer was calculated from all experiments and
      observed for any inhibition of virus. RESULTS: In initial experiments, matrix
      method for drug and virus concentration was employed. It was observed that the
      drug exhibited some response for 3log EID50 (egg infective dose) in few samples
      at 1:2 HA titer, but no response was observed at 4log EID50. In subsequent
      experiment, all the virus titers from 7log EID50 to 2log EID50 demonstrated
      positive HA titer of 1:64. However, the drug failed to exhibit any significant
      inhibition at any level of demonstrable virus titer. At all the concentrations,
      O. sanctum extracts were found to be safe. CONCLUSION: The embryonated egg model
      may be utilized further to screen other drugs, which possess direct inhibitory
      properties like neuraminidase inhibition, and O. sanctum does not inhibit the
      influenza virus in this model at the given concentration.

PMID- 24914315
TI  - Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial
      dysfunction in mice treated with D-galactose.
AB  - BACKGROUND: Silybum marianum has been used as herbal medicine for the treatment
      of liver disease, liver cirrhosis, and to prevent liver cancer in Europe and Asia
      since ancient times. Silybum marianum oil (SMO), a by-product of silymarin
      production, is rich in essential fatty acids, phospholipids, sterols, and vitamin
      E. However, it has not been very good development and use. OBJECTIVE: In the
      present study, we used olive oil as a control to investigate the antioxidant and
      anti-aging effect of SMO in D-galactose (D-gal)-induced aging mice. MATERIALS AND
      METHODS: D-gal was injected intraperitoneally (500 mg/kg body weight daily) for 7
      weeks while SMO was simultaneously administered orally. The triglycerides (TRIG)
      and cholesterol (CHOL) levels were estimated in the serum. Superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC),
      monoamine oxidase (MAO), malondialdehyde (MDA), caspase-3, and Bcl-2 were
      determined in the liver and brain. The activities of Na(+)-K(+)-adenosine
      triphosphatase (ATPase), Ca(2+)-Mg(2+)-ATPase, membrane potential (DeltaPsim),
      and membrane fluidity of the liver mitochondrial were estimated. RESULTS: SMO
      decreased levels of TRIG and CHOL in aging mice. SMO administration elevated the
      activities of SOD, GSH-Px, and T-AOC, which are suppressed by aging. The levels
      of MAO and MDA in the liver and brain were reduced by SMO administration in aging
      mice. Enzyme linked immunosorbent assay showed that SMO significantly decreased
      the concentration of caspase-3 and improved the activity of Bcl-2 in the liver
      and brain of aging mice. Furthermore, SMO significantly attenuated the D-gal
      induced liver mitochondrial dysfunction by improving the activities of Na(+)-K(+)
      ATPase, Ca(2+)-Mg(2+)-ATPase, membrane potential (DeltaPsim), and membrane
      fluidity. CONCLUSION: These results indicate that SMO effectively attenuated
      oxidative damage and improved apoptosis related factors as well as liver
      mitochondrial dysfunction in aging mice.

PMID- 24914316
TI  - Can Helicobacter pylori infection influence human reproduction?
AB  - Helicobacter pylori (H. pylori) infection could be associated with extra
      digestive diseases. Here, we report the evidences concerning the decrease in
      reproductive potential occurring in individuals infected by H. pylori, especially
      by strains expressing CagA. This infection is more prevalent in individuals with
      fertility disorders. Infected women have anti-H. pylori antibodies in cervical
      mucus and follicular fluid that may decrease sperm motility and cross react
      immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion.
      Infection by CagA positive organisms enhances the risk of preeclampsia, which is
      a main cause of foetus death. These findings are supported by the results of
      experimental infections of pregnant mice, which may cause reabsorption of a high
      number of foetuses and alter the balance between Th1 and Th2 cell response.
      Infected men have decreased sperm motility, viability and numbers of normally
      shaped sperm and augmented systemic levels of inflammatory cytokines, such as
      tumor necrosis factor-alpha, which may damage spermatozoa. In countries where
      parasitic infestation is endemic, detrimental effects of infection upon
      spermatozoa may not occur, because the immune response to parasites could
      determine a switch from a predominant Th1 type to Th2 type lymphocytes, with
      production of anti-inflammatory cytokines. In conclusion, the evidences gathered
      until now should be taken into consideration for future studies aiming to explore
      the possible role of H. pylori infection on human reproduction. 

PMID- 24914317
TI  - Helicobacter pylori: a chameleon-like approach to life.
AB  - Helicobacter pylori (H. pylori) is widely adaptable for colonization in human
      stomachs in more than half of the world's population. The microorganism is
      characterized by an unusual capability of arranging itself in both genotypic and
      phenotypic ways. Stressing conditions, including antimicrobial agents in sub
      inhibitory concentrations, facilitate entering the viable but nonculturable state
      in which bacterial cells acquire the coccoid form. This morphotype represents an
      important strategy for bacterial survival in unsuitable conditions and also
      allows escape from the immune system. H. pylori is capable of forming biofilm
      outside and inside the host. For the bacterial population, the sessile growth
      mode represents an ideal environment for gene rearrangement, as it allows the
      acquiring of important tools aimed to improve bacterial "fitness" and species
      preservation. Biofilm formation in H. pylori in the human host also leads to
      recalcitrance to antibiotic treatment, thus hampering eradication. These
      lifestyle changes of H. pylori allow for a "safe haven" for its survival and
      persistence according to different ecological niches, and strongly emphasize the
      need for careful H. pylori surveillance to improve management of the infection. 

PMID- 24914318
TI  - Immune responses to Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) infection is one of the most common infections in
      human beings worldwide. H. pylori express lipopolysaccharides and flagellin that
      do not activate efficiently Toll-like receptors and express dedicated effectors,
      such as gamma-glutamyl transpeptidase, vacuolating cytotoxin (vacA), arginase,
      that actively induce tolerogenic signals. In this perspective, H. pylori can be
      considered as a commensal bacteria belonging to the stomach microbiota. However,
      when present in the stomach, H. pylori reduce the overall diversity of the
      gastric microbiota and promote gastric inflammation by inducing Nod1-dependent
      pro-inflammatory program and by activating neutrophils through the production of
      a neutrophil activating protein. The maintenance of a chronic inflammation in the
      gastric mucosa and the direct action of virulence factors (vacA and cytotoxin
      associated gene A) confer pro-carcinogenic activities to H. pylori. Hence, H.
      pylori cannot be considered as symbiotic bacteria but rather as part of the
      pathobiont. The development of a H. pylori vaccine will bring health benefits for
      individuals infected with antibiotic resistant H. pylori strains and population
      of underdeveloped countries. 

PMID- 24914319
TI  - Overview of the phytomedicine approaches against Helicobacter pylori.
AB  - Helicobacter pylori (H. pylori) successfully colonizes the human stomach of the
      majority of the human population. This infection always causes chronic gastritis,
      but may evolve to serious outcomes, such as peptic ulcer, gastric carcinoma or
      mucosa-associated lymphoid tissue lymphoma. H. pylori first line therapy
      recommended by the Maastricht-4 Consensus Report comprises the use of two
      antibiotics and a proton-pomp inhibitor, but in some regions failure associated
      with this treatment is already undesirable high. Indeed, treatment failure is one
      of the major problems associated with H. pylori infection and is mainly
      associated with bacterial antibiotic resistance. In order to counteract this
      situation, some effort has been allocated during the last years in the
      investigation of therapeutic alternatives beyond antibiotics. These include
      vaccines, probiotics, photodynamic inactivation and phage therapy, which are
      briefly revisited in this review. A particular focus on phytomedicine, also
      described as herbal therapy and botanical therapy, which consists in the use of
      plant extracts for medicinal purposes, is specifically addressed, namely
      considering its history, category of performed studies, tested compounds, active
      principle and mode of action. The herbs already experienced are highly diverse
      and usually selected from products with a long history of employment against
      diseases associated with H. pylori infection from each country own folk medicine.
      The studies demonstrated that many phytomedicine products have an anti-H. pylori
      activity and gastroprotective action. Although the mechanism of action is far
      from being completely understood, current knowledge correlates the beneficial
      action of herbs with inhibition of essential H. pylori enzymes, modulation of the
      host immune system and with attenuation of inflammation. 

PMID- 24914321
TI  - Blood pressure and stature in Helicobacter pylori positive and negative persons.
AB  - To evaluate vital signs and body indices in Helicobacter pylori (H. pylori)
      positive and negative persons. A total of 22 centres entered the study. They were
      spread over the whole country, corresponding well to the geographical
      distribution of the Czech population. A total of 1818 subjects (aged 5-98 years)
      took part in the study, randomly selected out of 38147 subjects. H. pylori
      infection was investigated by means of a 13C-urea breath test. Data on height,
      weight, systolic and diastolic blood pressure and heart rate were collected at
      the clinics of general practitioners. The overall prevalence of H. pylori
      infection was 30.4% (402/1321) in adults (>= 18 year-old) and 5.2% (26/497) in
      children and adolescents (<= 17 year-old). Once adjusted for age and gender, only
      a difference in body mass index remained statistically significant with H. pylori
      positive adults showing an increase of 0.6 kg/m(2) in body mass index. Once
      adjusted for age and gender, we found a difference in height between H. pylori
      positive and H. pylori negative children and adolescents. On further adjustment
      for place of residence, this difference became statistically significant, with H.
      pylori positive children and adolescents being on average 3.5 cm shorter. H.
      pylori positive adults were significantly older compared to H. pylori negative
      subjects. Once adjusted for age and gender, H. pylori infection had no impact on
      body weight, body mass index and vital signs either in adults or children and
      adolescents. Chronic H. pylori infection appeared to be associated with short
      stature in children. H. pylori infection did not influence blood pressure, body
      weight and body mass index either in adults or children and adolescents. 

PMID- 24914322
TI  - Biofilm and Helicobacter pylori: from environment to human host.
AB  - Helicobacter pylori (H. pylori) is a Gram negative pathogen that selectively
      colonizes the human gastric epithelium. Over 50% of the world population is
      infected with H. pylori reaching up to 90% of infected individuals in developing
      countries. Nonetheless the increased impact upon public health care, its
      reservoir and the transmission pathway of the species has not been clearly
      established yet. Molecular studies allowed the detection of H. pylori in various
      aquatic environments, even forming biofilm in tap water distribution systems in
      several countries, suggesting a role of water as a possible reservoir of the
      pathogen. The persistence of human infection with H. pylori and the resistance of
      clinical isolates to commonly used antibiotics in eradication therapy have been
      related to the genetic variability of the species and its ability to develop
      biofilm, demonstrated both in vivo and in vitro experiments. Thus, during the
      last years, experimental work with this pathogen has been focused in the search
      for biofilm inhibitors and biofilm destabilizing agents. However, only two anti-
      H. pylori biofilm disrupting agents have been successfully used: Curcumin - a
      natural dye - and N-acetyl cysteine - a mucolytic agent used in respiratory
      diseases. The main goal of this review was to discuss the evidences available in
      the literature supporting the ability of H. pylori to form biofilm upon various
      surfaces in aquatic environments, both in vivo and in vitro. The results
      published and our own observations suggest that the ability of H. pylori to form
      biofilm may be important for surviving under stress conditions or in the spread
      of the infection among humans, mainly through natural water sources and water
      distribution systems. 

PMID- 24914320
TI  - Factors that mediate colonization of the human stomach by Helicobacter pylori.
AB  - Helicobacter pylori (H. pylori) colonizes the stomach of humans and causes
      chronic infection. The majority of bacteria live in the mucus layer overlying the
      gastric epithelial cells and only a small proportion of bacteria are found
      interacting with the epithelial cells. The bacteria living in the gastric mucus
      may act as a reservoir of infection for the underlying cells which is essential
      for the development of disease. Colonization of gastric mucus is likely to be key
      to the establishment of chronic infection. How H. pylori manages to colonise and
      survive in the hostile environment of the human stomach and avoid removal by
      mucus flow and killing by gastric acid is the subject of this review. We also
      discuss how bacterial and host factors may together go some way to explaining the
      susceptibility to colonization and the outcome of infection in different
      individuals. H. pylori infection of the gastric mucosa has become a paradigm for
      chronic infection. Understanding of why H. pylori is such a successful pathogen
      may help us understand how other bacterial species colonise mucosal surfaces and
      cause disease. 

PMID- 24914323
TI  - Role of dental plaque, saliva and periodontal disease in Helicobacter pylori
      infection.
AB  - Helicobacter pylori (H. pylori) infection is one of the most common bacterial
      infections in humans. Although H. pylori may be detected in the stomach of
      approximately half of the world's population, the mechanisms of transmission of
      the microorganism from individual to individual are not yet clear. Transmission
      of H. pylori could occur through iatrogenic, fecal-oral, and oral-oral routes,
      and through food and water. The microorganism may be transmitted orally and has
      been detected in dental plaque and saliva. However, the role of the oral cavity
      in the transmission and recurrence of H. pylori infection has been the subject of
      debate. A large number of studies investigating the role of oral hygiene and
      periodontal disease in H. pylori infection have varied significantly in terms of
      their methodology and sample population, resulting in a wide variation in the
      reported results. Nevertheless, recent studies have not only shown that the
      microorganism can be detected fairly consistently from the oral cavity but also
      demonstrated that the chances of recurrence of H. pylori infection is more likely
      among patients who harbor the organism in the oral cavity. Furthermore, initial
      results from clinical trials have shown that H. pylori-positive dyspeptic
      patients may benefit from periodontal therapy. This paper attempts to review the
      current body of evidence regarding the role of dental plaque, saliva, and
      periodontal disease in H. pylori infection. 

PMID- 24914324
TI  - Optimal treatment strategy for Helicobacter pylori: era of antibiotic resistance.
AB  - Standard triple therapy, consisting of a proton pump inhibitor, plus amoxicillin
      and clarithromycin, has been the most commonly used first-line treatment regimen
      for Helicobacter pylori (H. pylori) eradication for many years worldwide.
      However, as a result of increased resistance to antibiotics, H. pylori
      eradication rates with use of standard triple therapy have been declining and
      recently reached < 80% in many countries. Several new strategies to enhance the
      eradication rate of H. pylori have been studied. Currently, among the alternative
      first-line eradication regimens, concomitant and hybrid regimens have shown
      excellent results and could be the optimal treatment option. Although clinical
      usefulness of rescue therapy for patients in whom eradication of H. pylori with
      non-bismuth quadruple regimen has failed is unclear, levofloxacin-based quadruple
      therapy has shown promise as a rescue treatment. The choice of third-line therapy
      depends on factors such as the local pattern of antibiotic resistance, drug
      availability, and previous treatment. We hope that a simple method for detection
      of antibiotic susceptibility using polymerase chain reaction would be a possible
      alternative to administration of "tailored treatment" in the era of increasing
      prevalence of antimicrobial resistance. 

PMID- 24914326
TI  - Reduced genome size of Helicobacter pylori originating from East Asia.
AB  - Helicobacter pylori (H. pylori), a major pathogen colonizing the human stomach,
      shows great genetic variation. Comparative analysis of strains from different H.
      pylori populations revealed that the genome size of strains from East Asia
      decreased to 1.60 Mbp, which is significantly smaller than that from Europe or
      Africa. In parallel with the genome reduction, the number of protein coding genes
      was decreased, and the guanine-cytosine content was lowered to 38.9%. Elimination
      of non-essential genes by mutations is likely to be a major cause of the genome
      reduction. Bacteria with a small genome cost less energy. Thus, H. pylori strains
      from East Asia may have proliferation and growth advantages over those from
      Western countries. This could result in enhanced capacity of bacterial spreading.
      Therefore, the reduced genome size potentially contributes to the high prevalence
      of H. pylori in East Asia. 

PMID- 24914325
TI  - Helicobacter pylori eradication for preventing gastric cancer.
AB  - Helicobacter pylori (H. pylori) infection is a major risk factor for gastric
      cancer (GC) development, which is one of the most challenging malignant diseases
      worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori
      infection slowly induces chronic active gastritis, which progresses through the
      premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia,
      and then finally to GC. Although eradication of H. pylori is a reasonable
      approach for the prevention of GC, there have been some contradictory reports,
      with only some long-term follow-up data showing efficacy of this approach. The
      inconsistencies are likely due to the insufficient number of participants,
      relatively short follow-up periods, poor quality of study designs, and the degree
      and extent of preneoplastic changes at the time of H. pylori eradication. This
      review analyzes recent high-quality studies to resolve the discrepancies
      regarding the eradication of H. pylori for GC prevention. The relationship
      between H. pylori eradication and GC/precancerous lesions/metachronous GC is
      examined, and the cost-effectiveness of this strategy in the prevention of GC is
      assessed. Although it is assumed that eradication of H. pylori has the potential
      to prevent GC, the feasibility and appropriate timing of this strategy for cancer
      prevention remain to be determined. As a result, additional well-designed trials
      with longer follow-up periods are needed to clarify this issue. 

PMID- 24914327
TI  - Treatment of early gastric cancer in the Western World.
AB  - The incidence rate of gastric cancer is much higher in Asia than in the Western
      industrial nations. According to the different screening programs in Japan and
      Korea about fifty percent of treated patients had an early tumor stage. In
      contrast, European and American patients with gastric cancer had an advanced
      tumor stage. Therefore, the experience for the various therapeutic options for
      gastric cancer may be different between these regions. In this review we tried to
      point out the treatment modalities in Western industrial countries for early
      gastric cancer. 

PMID- 24914328
TI  - Pathohistological classification systems in gastric cancer: diagnostic relevance
      and prognostic value.
AB  - Several pathohistological classification systems exist for the diagnosis of
      gastric cancer. Many studies have investigated the correlation between the
      pathohistological characteristics in gastric cancer and patient characteristics,
      disease specific criteria and overall outcome. It is still controversial as to
      which classification system imparts the most reliable information, and therefore,
      the choice of system may vary in clinical routine. In addition to the most common
      classification systems, such as the Lauren and the World Health Organization
      (WHO) classifications, other authors have tried to characterize and classify
      gastric cancer based on the microscopic morphology and in reference to the
      clinical outcome of the patients. In more than 50 years of systematic
      classification of the pathohistological characteristics of gastric cancer, there
      is no sole classification system that is consistently used worldwide in
      diagnostics and research. However, several national guidelines for the treatment
      of gastric cancer refer to the Lauren or the WHO classifications regarding
      therapeutic decision-making, which underlines the importance of a reliable
      classification system for gastric cancer. The latest results from gastric cancer
      studies indicate that it might be useful to integrate DNA- and RNA-based features
      of gastric cancer into the classification systems to establish prognostic
      relevance. This article reviews the diagnostic relevance and the prognostic value
      of different pathohistological classification systems in gastric cancer. 

PMID- 24914329
TI  - Sentinel lymph node navigation surgery for early stage gastric cancer.
AB  - We attempted to evaluate the history of sentinel node navigation surgery (SNNS),
      technical aspects, tracers, and clinical applications of SNNS using Infrared Ray
      Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel
      lymph node (SLN) is defined as a first lymph node (LN) which receives cancer
      cells from a primary tumor. Reports on clinical application of SNNS for gastric
      cancers started to appear since early 2000s. Two prospective multicenter trials
      of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al
      reported that the endoscopic dual (dye and radioisotope) tracer method for SN
      biopsy was confirmed acceptable and effective when applied to the early-stage
      gastric cancer (EGC). We have previously reported the usefulness of SNNS in
      gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus
      Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence,
      clinical application of SNNS for EGC might lead us to avoid unnecessary LN
      dissection, which could preserve the patient's quality of life after operation.
      The most ideal method of SNNS should allow secure and accurate detection of SLN,
      and real time observation of lymphatic flow during operation. 

PMID- 24914330
TI  - Role of microRNAs in gastric cancer.
AB  - Although gastric cancer (GC) is one of the leading causes of cancer-related
      death, major therapeutic advances have not been made, and patients with GC still
      face poor outcomes. The prognosis of GC also remains poor because the molecular
      mechanisms of GC progression are incompletely understood. MicroRNAs (miRNAs) are
      noncoding RNAs that are associated with gastric carcinogenesis. Studies
      investigating the regulation of gene expression by miRNAs have made considerable
      progress in recent years, and abnormalities in miRNA expression have been shown
      to be associated with the occurrence and progression of GC. miRNAs contribute to
      gastric carcinogenesis by altering the expression of oncogenes and tumor
      suppressors, affecting cell proliferation, apoptosis, motility, and invasion.
      Moreover, a number of miRNAs have been shown to be associated with tumor type,
      tumor stage, and patient survival and therefore may be developed as novel
      diagnostic or prognostic markers. In this review, we discuss the involvement of
      miRNAs in GC and the mechanisms through which they regulate gene expression and
      biological functions. Then, we review recent research on the involvement of
      miRNAs in GC prognosis, their potential use in chemotherapy, and their effects on
      Helicobacter pylori infections in GC. A greater understanding of the roles of
      miRNAs in gastric carcinogenesis could provide insights into the mechanisms of
      tumor development and could help to identify novel therapeutic targets. 

PMID- 24914331
TI  - miRNA polymorphisms and risk of gastric cancer in Asian population.
AB  - miRNAs are endogenous 19- to 25-nt noncoding RNAs that can negatively regulate
      gene expression by directly cleaving target mRNA or by inhibiting its
      translation. Recent studies have revealed that miRNA plays a significant role in
      gastric cancer development either as a tumor suppressor gene or oncogene. miRNA
      single-nucleotide polymorphisms (SNPs), as a novel class of functional
      SNPs/polymorphisms, have been identified as candidate biomarkers for gastric
      cancer susceptibility. On the basis of recent data, the present review summarizes
      current knowledge of the functional effects of miRNA-SNPs and their importance as
      candidate gastric cancer biomarkers. Additionally, this review also includes a
      meta-analysis of the most frequently studied miRNA-SNPs in gastric cancer. 

PMID- 24914332
TI  - Molecular diagnosis and treatment of drug-resistant hepatitis B virus.
AB  - Oral antiviral agents have been developed in the last two decades for the
      treatment of chronic hepatitis B (CHB). However, antiviral resistance remains an
      important challenge for long-term CHB therapy. All of the clinically available
      oral antiviral agents are nucleoside or nucleotide analogues that target the
      activity of viral reverse transcriptase (RT), and all are reported to have
      resistant mutations. Since the hepatitis B virus (HBV) RT, like other viral
      polymerases, lacks proofreading activity, the emergence of drug-resistance occurs
      readily under selective pressure from the administration of antiviral agents. The
      molecular diagnosis of drug-resistant HBV is based on sequence variations, and
      current diagnostic methods include sequencing, restriction fragment polymorphism
      analysis, and hybridization. Here, we will discuss the currently available
      molecular diagnosis tools, in vitro phenotypic assays for validation of drug
      resistant HBV, and treatment options for drug-resistant HBV. 

PMID- 24914333
TI  - Hepatitis B virus infection and intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising
      from the peripheral intrahepatic bile duct epithelium. The incidence and
      mortality of ICC is markedly increasing over the past two decades worldwide,
      though the cause for this rise in incidence is unclear, thus intensifying the
      search for alternative etiological agents and pathogenetic mechanisms.
      Hepatolithiasis, primary sclerosing cholangitis, parasitic infection
      (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease,
      and chemical carcinogen exposure are thought to be the risk factors for ICC.
      Nevertheless, the majority of ICC patients do not have any of these risk factors,
      and none of the established risk factors can explain the recent increasing trend
      of ICC. Therefore, identifying other risk factors may lead to the prevention and
      early detection of ICC. Chronic hepatitis B virus (HBV) infection is the
      predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review
      discusses the evidence implicating chronic HBV infection as a likely etiology of
      ICC and the pathogenetic mechanisms that might be involved. 

PMID- 24914334
TI  - Optimization therapy for the treatment of chronic hepatitis B.
AB  - Chronic hepatitis B (CHB) is currently medically managed with either interferon
      alpha or one of the five nucleos(t)ide analogs. However, there are still a large
      number of CHB patients whose response to the above therapies remains less than
      satisfactory, and their incomplete or non-response to antiviral therapies has
      plagued clinicians worldwide. In recent years, a newly proposed optimization
      therapy has provided us with a new approach to solve this problem. The key points
      in this optimization therapy are to initiate antiviral therapy with an
      appropriate agent at the correct time point, and to adjust treatments in patients
      with poor early responses by adding a second agent or switching to another more
      potent agent. In this review, we summarize recent developments in optimization
      therapy for the treatment of CHB, and provide an outlook for future research in
      this field. 

PMID- 24914335
TI  - Deep vein thrombosis and pulmonary embolism in cirrhotic patients: systematic
      review.
AB  - Patients with liver cirrhosis were traditionally believed to be protected against
      development of blood clots. Lately, studies have shown that these patients may
      probably be at an increased risk of venous thrombotic complications. Although the
      hemostatic changes in the chronic liver disease patients and the factors that may
      predict bleeding vs thrombotic complications remains an area of active research,
      it is believed that the coagulation cascade is delicately balanced in these
      patients because of parallel reduced hepatic synthesis of pro and anticoagulant
      factors. Thrombotic state in cirrhotic patients is responsible for not only
      portal or non-portal thrombosis [deep vein thrombosis (DVT) and pulmonary
      embolism (PE)]; it has also been associated with progression of liver fibrosis.
      The use of anticoagulants in cirrhosis patients is a challenging, and often a
      scary situation. This review summarizes the current literature on the prevalence
      of venous thrombosis (DVT and PE), risk factors and safety of prophylactic and
      therapeutic anticoagulation in patients with chronic liver disease. 

PMID- 24914336
TI  - Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis is a multifactor autoimmune disease characterized by
      hepatic and systemic manifestations, with immune system dysregulation and
      abnormalities in the hepatic metabolism of bile salts, lipids, and nutrients, as
      well as destruction of membrane lipids and mitochondrial dysfunction. Both
      oxidative and nitrosative stress are associated with ongoing manifestations of
      the disease. In particular, abnormalities in nitric oxide metabolism and thiol
      oxidation already occur at early stages, thus leading to the hypothesis that
      these biochemical events play a pathogenic role in primary biliary cirrhosis.
      Moreover, the association of these metabolic abnormalities with the progression
      of the disease may indicate some biochemical parameters as early diagnostic
      markers of disease evolution, and may open up the potential for pharmacological
      intervention to inhibit intra- and extra-cellular stress events for resuming
      hepatocellular functions. The following paragraphs summarize the current
      knowledge by outlining molecular mechanisms of the disease related to these
      stress events. 

PMID- 24914337
TI  - Antitubercular therapy in patients with cirrhosis: challenges and options.
AB  - Tuberculosis (TB) has been a human disease for centuries. Its frequency is
      increased manyfold in patients with liver cirrhosis. The gold standard of TB
      management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and
      ethambutol. Although good results are seen with this treatment in general, the
      management of patients with underlying cirrhosis is a challenge. The underlying
      depressed immune response results in alterations in many diagnostic tests. The
      tests used for latent TB have many flaws in this group of patients. Three of four
      first-line antitubercular drugs are hepatotoxic and baseline liver function is
      often disrupted in patients with underlying cirrhosis. Frequency of
      hepatotoxicity is increased in patients with liver cirrhosis, frequently leading
      to severe liver failure. There are no established guidelines for the treatment of
      TB in relation to the severity of liver disease. There is no consensus on the
      frequency of liver function tests required or the cut-off used to define
      hepatotoxicity. No specific treatment exists for prevention or treatment of
      hepatotoxicity, making monitoring even more important. A high risk of multidrug
      resistant TB is another major worry due to prolonged and interrupted treatment. 

PMID- 24914339
TI  - Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and
      portal hypertension.
AB  - Since the first laparoscopic splenectomy (LS) was reported in 1991, LS has become
      the gold standard for the removal of normal to moderately enlarged spleens in
      benign conditions. Compared with open splenectomy, fewer postsurgical
      complications and better postoperative recovery have been observed, but LS is
      contraindicated for hypersplenism secondary to liver cirrhosis in many
      institutions owing to technical difficulties associated with splenomegaly, well
      developed collateral circulation, and increased risk of bleeding. With the
      improvements of laparoscopic technique, the concept is changing. This article
      aims to give an overview of the latest development in laparoscopic splenectomy
      for hypersplenism secondary to liver cirrhosis and portal hypertension. Despite a
      lack of randomized controlled trial, the publications obtained have shown that
      with meticulous surgical techniques and advanced instruments, LS is a technically
      feasible, safe, and effective procedure for hypersplenism secondary to cirrhosis
      and portal hypertension and contributes to decreased blood loss, shorter hospital
      stay, and less impairment of liver function. It is recommended that the dilated
      short gastric vessels and other enlarged collateral circulation surrounding the
      spleen be divided with the LigaSure vessel sealing equipment, and the splenic
      artery and vein be transected en bloc with the application of the endovascular
      stapler. To support the clinical evidence, further randomized controlled trials
      about this topic are necessary. 

PMID- 24914340
TI  - Acute pancreatitis: the stress factor.
AB  - Acute pancreatitis is an inflammatory disorder of the pancreas that may cause
      life-threatening complications. Etiologies of pancreatitis vary, with gallstones
      accounting for the majority of all cases, followed by alcohol. Other causes of
      pancreatitis include trauma, ischemia, mechanical obstruction, infections,
      autoimmune, hereditary, and drugs. The main events occurring in the pancreatic
      acinar cell that initiate and propagate acute pancreatitis include inhibition of
      secretion, intracellular activation of proteases, and generation of inflammatory
      mediators. Small cytokines known as chemokines are released from damaged
      pancreatic cells and attract inflammatory cells, whose systemic action ultimately
      determined the severity of the disease. Indeed, severe forms of pancreatitis may
      result in systemic inflammatory response syndrome and multiorgan dysfunction
      syndrome, characterized by a progressive physiologic failure of several
      interdependent organ systems. Stress occurs when homeostasis is threatened, and
      stressors can include physical or mental forces, or combinations of both.
      Depending on the timing and duration, stress can result in beneficial or harmful
      consequences. While it is well established that a previous acute-short-term
      stress decreases the severity of experimentally-induced pancreatitis, the
      worsening effects of chronic stress on the exocrine pancreas have received
      relatively little attention. This review will focus on the influence of both
      prior acute-short-term and chronic stress in acute pancreatitis. 

PMID- 24914338
TI  - Autophagy in hepatitis C virus-host interactions: potential roles and therapeutic
      targets for liver-associated diseases.
AB  - Autophagy is a lysosome-associated, degradative process that catabolizes
      cytosolic components to recycle nutrients for further use and maintain cell
      homeostasis. Hepatitis C virus (HCV) is a major cause of chronic hepatitis, which
      often leads to end-stage liver-associated diseases and is a significant burden on
      worldwide public health. Emerging lines of evidence indicate that autophagy plays
      an important role in promoting the HCV life cycle in host cells. Moreover, the
      diverse impacts of autophagy on a variety of signaling pathways in HCV-infected
      cells suggest that the autophagic process is required for balancing HCV-host cell
      interactions and involved in the pathogenesis of HCV-related liver diseases.
      However, the detailed molecular mechanism underlying how HCV activates autophagy
      to benefit viral growth is still enigmatic. Additionally, how the autophagic
      response contributes to disease progression in HCV-infected cells remains largely
      unknown. Hence, in this review, we overview the interplay between autophagy and
      the HCV life cycle and propose possible mechanisms by which autophagy may promote
      the pathogenesis of HCV-associated chronic liver diseases. Moreover, we outline
      the related studies on how autophagy interplays with HCV replication and discuss
      the possible implications of autophagy and viral replication in the progression
      of HCV-induced liver diseases, e.g., steatosis and hepatocellular carcinoma.
      Finally, we explore the potential therapeutics that target autophagy to cure HCV
      infection and its related liver diseases. 

PMID- 24914341
TI  - Intervention on toll-like receptors in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDA) is a devastating disease with pronounced
      morbidity and a high mortality rate. Currently available treatments lack
      convincing cost-efficiency determinations and are in most cases not associated
      with relevant success rate. Experimental stimulation of the immune system in
      murine PDA models has revealed some promising results. Toll-like receptors (TLRs)
      are pillars of the immune system that have been linked to several forms of
      malignancy, including lung, breast and colon cancer. In humans, TLRs are
      expressed in the pancreatic cancer tissue and in several cancer cell lines,
      whereas they are not expressed in the normal pancreas. In the present review, we
      explore the current knowledge concerning the role of different TLRs associated to
      PDA. Even if almost all known TLRs are expressed in the pancreatic cancer
      microenvironment, there are only five TLRs suggested as possible therapeutic
      targets. Most data points at TLR2 and TLR9 as effective tumor markers and
      agonists could potentially be used as e.g. future adjuvant therapies. The
      elucidation of the role of TLR3 in PDA is only in its initial phase. The
      inhibition/blockage of TLR4-related pathways has shown some promising effects,
      but there are still many steps left before TLR4 inhibitors can be considered as
      possible therapeutic agents. Finally, TLR7 antagonists seem to be potential
      candidates for therapy. Independent of their potential in immunotherapies, all
      existing data indicate that TLRs are strongly involved in the pathophysiology and
      development of PDA. 

PMID- 24914342
TI  - MicroRNAs: New therapeutic targets for intestinal barrier dysfunction.
AB  - Defects in intestinal barrier function characterized by an increase in intestinal
      permeability contribute to intestinal inflammation. Growing evidence has shown
      that an increase in intestinal permeability has a pathogenic role in diseases
      such as inflammatory bowel disease (IBD) and celiac disease, and functional bowel
      disorders such as irritable bowel syndrome. Therefore, clarification of the
      inflammatory responses, the defense pathway and the corresponding regulatory
      system is essential and may lead to the development of new therapies. MicroRNAs
      (miRNAs) are small (19-22 nt) noncoding RNA molecules that regulate genes at the
      post-transcriptional level by base-pairing to specific messenger RNAs for
      degradation to repress translation. Recent studies suggested that miRNAs are
      important in the immune response and mediate a critical role in multiple immune
      response-related disorders. Based on these discoveries, attention has been
      focused on understanding the role of miRNAs in regulating intestinal barrier
      dysfunction, especially in IBD. Here, we provide a review of the most recent
      state-of-the-art research on miRNAs in intestinal barrier dysfunction. 

PMID- 24914343
TI  - Identification of biomarkers for hepatocellular carcinoma by semiquantitative
      immunocytochemistry.
AB  - AIM: To investigate the expression of key biomarkers in hepatoma cell lines,
      tumor cells from patients' blood samples, and tumor tissues. METHODS: We
      performed the biomarker tests in two steps. First, cells plated on coverslips
      were used to assess biomarkers, and fluorescence intensities were calculated
      using the NIH Image J software. The measured values were analyzed using the SPSS
      19.0 software to make comparisons among eight cell lines. Second, eighty-four
      individual samples were used to assess the biomarkers' expression. Negative
      enrichment of the blood samples was performed, and karyocytes were isolated and
      dropped onto pre-treated glass slides for further analysis by immunofluorescence
      staining. Fluorescence intensities were compared among hepatocellular carcinoma
      (HCC) patients, chronic HBV-infected patients, and healthy controls following
      methods similar to those used for cell lines. The relationships between the
      expression of biomarkers and clinical pathological parameters were analyzed by
      Spearman rank correlation tests. In addition, we studied the distinct biomarkers'
      expression with three-dimensional laser confocal microscopy reconstructions, and
      Kaplan-Meier survival analysis was performed to understand the clinical
      significance of these biomarkers. RESULTS: Microscopic examination and
      fluorescence intensity calculations indicated that cytokeratin 8/18/19 (CK)
      expression was significantly higher in six of the seven HCC cell lines examined
      than in the control cells, and the expression levels of asialoglycoprotein
      receptor (ASGPR) and glypican-3 (GPC3) were higher in all seven HCC cell lines
      than in the control. Cells obtained from HCC patients' blood samples also
      displayed significantly higher expression levels of ASGPR, GPC3, and CK than
      cells from chronic HBV-infected patients or healthy controls; these proteins may
      be valuable surface biomarkers for identifying HCC circulating tumor cells
      isolated and enriched from the blood samples. The stem cell-like and epithelial
      mesenchymal transition-related biomarkers could be detected on the karyocyte
      slides. ASGPR and GPC3 were expressed at high levels, and thus three-dimensional
      reconstructions were used to observe their expression in detail. This analysis
      indicated that GPC3 was localized in the cytoplasm and membrane, but that ASGPR
      had a polar localization. Survival analyses showed that expression of GPC3 and
      ASGPR is associated with a patient's overall survival (OS). CONCLUSION: ASGPR,
      GPC3, and CK may be valuable HCC biomarkers for CTC detection; the expression of
      ASGPR and GPC3 might be helpful for understanding patients' OS.

PMID- 24914344
TI  - Down-regulated gamma-catenin expression is associated with tumor aggressiveness
      in esophageal cancer.
AB  - AIM: To evaluate the significance of gamma-catenin in clinical pathology,
      cellular function and signaling mechanism in esophageal squamous cell carcinoma
      (ESCC). METHODS: The mRNA expression of gamma-catenin was detected by real-time
      quantitative reverse transcription-polymerase chain reaction in 95 tissue
      specimens and evaluated for association with the clinicopathologic
      characteristics and survival time of patients with ESCC. siRNAs against human
      gamma-catenin were used to inhibit gamma-catenin expression. Hanging drop
      aggregation assay and dispase-based dissociation assay were performed to detect
      the effect of gamma-catenin on ESCC cell-cell adhesion. Transwell assay was
      performed to determine cell migration. Luciferase-based transcriptional reporter
      assay (TOPflash) was used to measure beta-catenin-dependent transcription in
      cells with reduced gamma-catenin expression. The expression and subcellular
      localizations of beta-catenin and E-cadherin were examined using Western blot and
      immunofluorescence analysis. RESULTS: gamma-catenin mRNA expression was
      significantly associated with tumor histological grade (P = 0.017) in ESCC.
      Kaplan-Meier survival analysis showed that gamma-catenin expression levels had an
      impact on the survival curve, with low gamma-catenin indicating worse survival (P
      = 0.003). The multivariate Cox regression analysis demonstrated that gamma
      catenin was an independent prognostic factor for survival. Experimentally,
      silencing gamma-catenin caused defects in cell-cell adhesion and a concomitant
      increase in cell migration in both KYSE150 and TE3 ESCC cells. Analysis of Wnt
      signaling revealed no activation event associated with gamma-catenin expression.
      Total beta-catenin and Triton X-100-insoluble beta-catenin were significantly
      reduced in the gamma-catenin-specific siRNA-transfected KYSE150 and TE3 cells,
      whereas Triton X-100-soluble beta-catenin was not altered. Moreover, knocking
      down gamma-catenin expression resulted in a significant decrease of E-cadherin
      and Triton X-100-insoluble desmocollin-2, along with reduced beta-catenin and E
      cadherin membrane localization in ESCC cells. CONCLUSION: gamma-catenin is a
      tumor suppressor in ESCC and may serve as a prognostic marker. Dysregulated
      expression of gamma-catenin may play important roles in ESCC progression.

PMID- 24914345
TI  - Changes in intestinal microflora in rats with acute respiratory distress
      syndrome.
AB  - AIM: To implement high-throughput 16S rDNA sequencing to study microbial
      diversity in the fecal matter of rats with acute lung injury/acute respiratory
      distress syndrome (ALI/ARDS). METHODS: Intratracheal instillation of
      lipopolysaccharide was used to induce ALI, and the pathological changes in the
      lungs and intestines were observed. D-lactate levels and diamine oxidase (DAO)
      activities were determined by enzymatic spectrophotometry. The fragments
      encompassing V4 16S rDNA hypervariable regions were PCR amplified from fecal
      samples, and the PCR products of V4 were sequenced by Illumina MiSeq. RESULTS:
      Increased D-lactate levels and DAO activities were observed in the model group (P
      < 0.01). Sequencing results revealed the presence of 3780 and 4142 species in the
      control and model groups, respectively. The percentage of shared species was
      18.8419%. Compared with the control group, the model group had a higher diversity
      index and a lower number of species of Fusobacteria (at the phylum level),
      Helicobacter and Roseburia (at the genus level) (P < 0.01). Differences in
      species diversity, structure, distribution and composition were found between the
      control group and early ARDS group. CONCLUSION: The detection of specific
      bacteria allows early detection and diagnosis of ALI/ARDS.

PMID- 24914346
TI  - A pilot proof-of-concept study of a modified device for one-step endoscopic
      ultrasound-guided biliary drainage in a new experimental biliary dilatation
      animal model.
AB  - AIM: To evaluate the technical feasibility of a modified tapered metal tip and
      low profile introducer for one-step endoscopic ultrasound (EUS)-guided biliary
      drainage (EUS-BD) in a new experimental biliary dilatation porcine model.
      METHODS: A novel dedicated device for one-step EUS-guided biliary drainage system
      (DEUS) introducer has size 3F tapered catheter with size 4F metal tip for simple
      puncture of the intestinal wall and liver parenchyma without graded dilation. A
      self-expandable metal stent, consisting of both uncovered and nitinol-covered
      portions, was preloaded into DEUS introducer. After establishment of a biliary
      dilatation model using endoscopic hemoclips or band ligation with argon plasma
      coagulation in 9 mini-pigs, EUS-BD using a DEUS was performed following 19-G
      needle puncture without the use of fistula dilation devices. RESULTS: One-step
      EUS-BD was technically successful in seven pigs [7/9 (77.8%) as intention to
      treat] without the aid of devices for fistula dilation from the high body of
      stomach or far distal esophagus to the intrahepatic (n = 2) or common hepatic (n
      = 5) duct. Primary technical failure occurred in two cases that did not show
      adequate biliary dilatation. In seven pigs with a successful bile duct
      dilatation, the technical success rate was 100% (7/7 as per protocol). Median
      procedure time from confirmation of the dilated bile duct to successful placement
      of a metallic stent was 10 min (IQR; 8.9-18.1). There were no immediate procedure
      related complications. CONCLUSION: Modified tapered metal tip and low profile
      introducer may be technically feasible for one-step EUS-BD in experimental
      porcine model.

PMID- 24914347
TI  - ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic
      gallstones.
AB  - AIM: To investigate the contribution of ABCB4 mutations to pediatric idiopathic
      gallstone disease and the potential of hormonal contraceptives to prompt clinical
      manifestations of multidrug resistance protein 3 deficiency. METHODS: Mutational
      analysis of ABCB4, screening for copy number variations by multiplex ligation
      dependent probe amplification, genotyping for low expression allele c.1331T>C of
      ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with
      cholesterol gallstones in adults was performed in 35 pediatric subjects with
      idiopathic gallstones who fulfilled the clinical criteria for low phospholipid
      associated cholelithiasis syndrome (LPAC, OMIM #600803) and in 5 young females
      with suspected LPAC and their families (5 probands, 15 additional family
      members). The probands came to medical attention for contraceptive-associated
      intrahepatic cholestasis. RESULTS: A possibly pathogenic variant of ABCB4 was
      found only in one of the 35 pediatric subjects with idiopathic cholesterol
      gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and
      another one was highly suspected to carry predictably pathogenic mutations in
      ABCB4. Among these 16, however, none developed gallstones in childhood. In 5
      index patients, all young females carrying at least one pathogenic mutation in
      one allele of ABCB4, manifestation of LPAC as intrahepatic cholestasis with
      elevated serum activity of gamma-glutamyltransferase was induced by hormonal
      contraceptives. Variants ABCB11 c.1331T>C and ABCG8 c.55G>C were not
      significantly overrepresented in the 35 examined patients with suspect LPAC.
      CONCLUSION: Clinical criteria for LPAC syndrome caused by mutations in ABCB4
      cannot be applied to pediatric patients with idiopathic gallstones. Sexual
      immaturity even prevents manifestation of LPAC.

PMID- 24914348
TI  - Prognostic significance of SUVmax and serum carbohydrate antigen 19-9 in
      pancreatic cancer.
AB  - AIM: To investigate the prognostic significance of pretreatment standardized
      maximum uptake value (SUVmax) and serum carbohydrate antigen (CA)19-9 in
      pancreatic cancer. METHODS: From January 2007 to October 2011, 80 consecutive
      patients with pancreatic cancer who received positron emission/computed
      tomography before any treatment were enrolled in this study. The pretreatment
      SUVmax and CA19-9 level of the primary pancreatic tumor were obtained and
      compared with clinicopathological and prognostic factors. Student's t test for
      unpaired data was used to analyze the differences between two groups. Univariate
      analysis and Cox proportional hazards regression were used to examine the
      independent effects of each significant variable. Survival was analyzed by the
      Kaplan-Meier method. RESULTS: There was a significant correlation between both
      the SUVmax and serum CA19-9 of pancreatic cancer and R0 surgical resection (P =
      0.043 and P = 0.007). Lymph node metastasis was associated with SUVmax (P =
      0.017), but not serum CA19-9 (P = 0.172). On the contrary, the tumor stage was
      significantly related to serum CA19-9 (P = 0.035), but not SUVmax (P = 0.110).
      The univariate analysis showed that survival time was significantly related to
      tumor stage (P < 0.001), lymph node metastasis (P = 0.043), R0 surgical resection
      (P < 0.001), serum CA19-9 (P = 0.001), SUVmax (P < 0.001) and SUVmax plus CA19-9
      (P = 0.002). Multivariate analysis clearly showed that only tumor stage (hazard
      ratio = 0.452; P = 0.020) was an independent prognostic factor for overall
      survival in pancreatic cancer. Higher SUVmax or CA19-9 showed worse prognosis. We
      found that high serum CA19-9 plus SUVmax was the most significant variable.
      CONCLUSION: Higher pretreatment SUVmax and serum CA19-9 indicates poor prognosis.
      SUVmax plus serum CA19-9 is the most significant variable in predicting survival.

PMID- 24914349
TI  - Late biliary complications in human alveolar echinococcosis are associated with
      high mortality.
AB  - AIM: To evaluate the incidence of late biliary complications in non-resectable
      alveolar echinococcosis (AE) under long-term chemotherapy with benzimidazoles.
      METHODS: Retrospective analysis of AE patients with biliary complications
      occurring more than three years after the diagnosis of AE. We compared
      characteristics of patients with and without biliary complications, analyzed
      potential risk factor for biliary complications and performed survival analyses.
      RESULTS: Ninety four of 148 patients with AE in Zurich had non-resectable AE
      requiring long-term benzimidazole chemotherapy, of which 26 (28%) patients
      developed late biliary complications. These patients had a median age of 55.5
      (35.5-65) years at diagnosis of AE and developed biliary complications after 15
      (8.25-19) years of chemotherapy. The most common biliary complications during
      long-term chemotherapy were late-onset cholangitis (n = 14), sclerosing
      cholangitis-like lesions (n = 8), hepatolithiasis (n = 5), affection of the
      common bile duct (n = 7) and secondary biliary cirrhosis (n = 7). Thirteen of the
      26 patients had undergone surgery (including 12 resections) before chemotherapy.
      Previous surgery was a risk factor for late biliary complications in linear
      regression analysis (P = 0.012). CONCLUSION: Late biliary complications can be
      observed in nearly one third of patients with non-resectable AE, with previous
      surgery being a potential risk factor. After the occurrence of late biliary
      complications, the median survival is only 3 years, suggesting that late biliary
      complications indicate a poor prognostic outcome.

PMID- 24914350
TI  - Frequency of HER2/neu overexpression in adenocarcinoma of the gastrointestinal
      system.
AB  - AIM: To determine the frequency of HER2/neu protein overexpression in gastric
      (group A), small intestine (group B), and colorectal (group C) adenocarcinoma.
      METHODS: A descriptive, cross-sectional study was performed on 50 cases of
      gastrointestinal adenocarcinoma (stomach, small intestine, and colorectal); 11
      from group A, 8 from group B, and 31 from group C. The samples were grossed and
      processed in the pathology department, and sections were stained with HE
      (hematoxylin and eosin stain) for histopathological confirmation of malignancy
      (well-differentiated, moderately-differentiated, and poorly-differentiated). The
      confirmed samples were processed for immunomarker study of HER2/neu. RESULTS:
      HER2/neu protein overexpression was found in 33 (66%) patients overall (P =
      0.000). Out of 33 HER2/neu positive subjects, 23 (69.6%) were from group C, while
      the remaining 10 (30%) were from group A. None of the patients from group B had
      positive HER2/neu protein overexpression. No protein overexpression or membrane
      staining in < 10% tumor cells was observed in 17 (34%) patients, which were
      labeled as score "0" and considered negative for HER2/neu protein overexpression.
      Faint/weak staining (in >= 10% of tumors cells) were observed in 8 (16%) patients
      and given the "1+" score. Similarly 13 (26%) patients reported moderate staining
      (in >= 10% tumor cells) and were thus labeled as "2+", and strong staining (in >=
      10% tumors cells), labeled as "3+", was observed in 12 (24%) patients. Out of 50
      patients, 26 (52%) were suffering from grade-II malignancy, 16 (32%) from grade
      I, and 8 (16%) from grade-III. There was highly significant association between
      tumor grades and HER2/neu protein overexpression (P = 0.0000). CONCLUSION:
      HER2/neu protein is credibly overexpressed in colon and gastric adenocarcinomas
      in immunohistochemistry. There is significant association between grade of tumor
      and HER2/neu protein overexpression.

PMID- 24914351
TI  - Determining hepatitis C virus genotype distribution among high-risk groups in
      Iran using real-time PCR.
AB  - AIM: To assess hepatitis C virus (HCV) genotype patterns among high-risk Iranian
      groups, using real-time RT-PCR. METHODS: In this study, we evaluated the
      distribution of different HCV genotypes among injection drug users and other high
      risk groups over a 4-year period (from 2009 to 2012) using real-time polymerase
      chain reaction (PCR). Sera from 888 HCV-infected patients residing in southern
      and southwest Iran were genotyped using real-time PCR with common primers and
      specific probes. These patients were grouped into distinct exposure categories.
      Illicit drug users constituted the primary group and were further evaluated for
      HCV genotype distribution and parameters such as age range. RESULTS: Of the
      examined HCV-infected patients, 62% were substance abusers, although the route of
      transmission could not be determined in approximately 30% of these patients. HCV
      genotyping revealed that Gt1 was the most prevalent genotype among the drug users
      as well as among patients with thalassemia, hemophilia, solid organ recipients
      and those on hemodialysis. Mixed infections were only seen in addict groups,
      where Gt2 genotype was also found. The highest frequencies in HCV-positive addict
      patients were observed in the 31-40 age group. Our research also showed that the
      addiction age has increased, whereas the addiction rate has dropped in this
      region. Most illicit drug users had more than one risk factor such as tattoo
      and/or a history of imprisonment. CONCLUSION: This study revealed that the most
      common HCV-infection route and HCV-genotype in southern and southwest Iran was
      illicit drug abuse and Gt1, respectively.

PMID- 24914352
TI  - Histological changes of gastric mucosa after Helicobacter pylori eradication: a
      systematic review and meta-analysis.
AB  - AIM: To systematically review pathological changes of gastric mucosa in gastric
      atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori)
      eradication. METHODS: A systematic search was made of PubMed, Web of Science,
      EMBASE, ClinicalTrials.gov, OVID and the Cochran Library databases for articles
      published before March 2013 pertaining to H. pylori and gastric premalignant
      lesions. Relevant outcomes from articles included in the meta-analysis were
      combined using Review Manager 5.2 software. A Begg's test was applied to test for
      publication bias using STATA 11 software. chi(2) and I(2) analyses were used to
      assess heterogeneity. Analysis of data with no heterogeneity (P > 0.1, I (2) <
      25%) was carried out with a fixed effects model, otherwise the causes of
      heterogeneity were first analyzed and then a random effects model was applied.
      RESULTS: The results of the meta-analysis showed that the pooled weighted mean
      difference (WMD) with 95%CI was 0.23 (0.18-0.29) between eradication and non
      eradication of H. pylori infection in antral IM with a significant overall effect
      (Z = 8.19; P <0.00001) and no significant heterogeneity (chi(2) = 27.54, I(2) =
      16%). The pooled WMD with 95%CI was -0.01 (-0.04-0.02) for IM in the corpus with
      no overall effect (Z = 0.66) or heterogeneity (chi(2) = 14.87, I(2) =0%) (fixed
      effects model). In antral GA, the pooled WMD with 95% CI was 0.25 (0.15-0.35)
      with a significant overall effect (Z = 4.78; P < 0.00001) and significant
      heterogeneity (chi(2) = 86.12, I(2) = 71%; P < 0.00001). The pooled WMD with 95%
      CI for GA of the corpus was 0.14 (0.04-0.24) with a significant overall effect (Z
      = 2.67; P = 0.008) and significant heterogeneity (chi(2) = 44.79, I(2) = 62%; P =
      0.0003) (random effects model). CONCLUSION: H. pylori eradication strongly
      correlates with improvement in IM in the antrum and GA in the corpus and antrum
      of the stomach.

PMID- 24914353
TI  - TNF inhibitors to treat ulcerative colitis in a metastatic breast cancer patient:
      a case report and literature review.
AB  - Adalimumab (ADA) is a tumor necrosis factor (TNF) inhibitor, used for the
      treatment of inflammatory bowel disease. Previous studies have reported an
      increased risk of cancer following exposure to TNF inhibitors, but little has
      been reported for patients with cancer receiving TNF-inhibitor treatment. We
      present a female patient with metastatic breast cancer and ulcerative colitis
      (UC) who was treated with ADA. A 54-year-old African American female with a past
      history of left-sided breast cancer (BC) diagnosed at age 30 was initially
      treated with left-breast lumpectomy, axillary dissection, followed by
      chemotherapy and radiation therapy. Years after initial diagnosis, she developed
      recurrent, bilateral BC and had bilateral mastectomy. Subsequent restaging
      computed tomography (CT) scan demonstrated distant metastases to the bone and
      lymph nodes. Three years into her treatment of metastatic breast cancer, she was
      diagnosed with UC by colonoscopy. Her UC was not controlled for 5 mo with 5
      aminosalicylates. Subcutaneous ADA was started and resulted in dramatic
      improvement of UC. Four months after starting ADA, along with ongoing
      chemotherapy, restaging CT scan showed resolution of the previously seen
      metastatic lymph nodes. Bone scan and follow-up positron emission tomography/CT
      scans performed every 6 mo indicated the stability of healed metastatic bone
      lesions for the past 3 years on ADA. While TNF-alpha inhibitors could
      theoretically promote further metastases in patients with prior cancer, this is
      the first report of a patient with metastatic breast cancer in whom the cancer
      has remained stable for 3 years after ADA initiation for UC. 

PMID- 24914354
TI  - Two rare gastric hamartomatous inverted polyp cases suggest the pathogenesis of
      growth.
AB  - Gastric hamartomatous inverted polyps (GHIP) are difficult to diagnose accurately
      because of inversion into the submucosal layer. GHIP are diagnosed using the
      pathological characteristics of the tumor, including the fibroblast cells, smooth
      muscle, nerve components, glandular hyperplasia, and cystic gland dilatation.
      Although Peutz-Jeghers syndrome, juvenile polyposis, and Cowden disease are
      hereditary, it is rare to encounter 2 cases of monostotic and asymptomatic
      gastric hamartomas. The pathogeneses of hamartomatous inverted polyps and
      inverted hyperplastic polyps remain controversial because of the paucity of
      reported cases. There are 3 hypotheses regarding the pathogenesis of complete
      gastric inverted polyps. Based on our experience with 2 successive, rare GHIP
      cases, we affirm the hypothesis that after a hamartomatous change occurs in the
      submucosal layer, some of these components are exposed to the gastric mucosa and,
      consequently, form a hypertrophic lesion. In Case 1, our hypothesis explains why
      a tiny hypertrophic change was first detected on the top of the submucosal tumor
      using a detailed narrow band imaging-magnified endoscopy. There was no
      confirmation that the milky white mucous and calcification structures were
      exuding directly from the biopsy site like Case 1, and in Case 2 the presence of
      this mucous was indirectly confirmed during an endoscopic submucosal dissection
      (ESD). Regarding the pathogenesis of GHIP, a submucosal hamartomatous change may
      occur prior to the growth of hypertrophic portions. An en bloc resection using
      ESD is recommended for treatment. 

PMID- 24914355
TI  - Transmesosigmoid hernia: case report and review of literature.
AB  - Transmesosigmoid hernia has previously been considered as a rare condition. The
      clinical symptoms can be nonspecific. Here, we report a case of acute intestinal
      obstruction because of transmesosigmoid hernia. In addition, after a
      comprehensive review of PubMed and China National Knowledge Infrastructure, we
      present a review of 22 cases of transmesosigmoid hernia. We summarize several
      valuable clinical features that help early recognition of transmesosigmoid
      hernia. As a result of easy strangulation, in patients without a history of
      surgery or abdominal inflammation who present with symptoms of progressive or
      persistent small bowel obstruction (SBO), surgeons should consider the
      possibility of transmesosigmoid hernia. In addition, based on our data, in
      patients with SBO because of transmesosigmoid hernia, the defect is usually 2-5
      cm in diameter. Furthermore, because of the high risk of strangulation with
      transmesosigmoid hernia, it is mandatory to reassess the condition timely and
      periodically when patients receive conservative treatment. 

PMID- 24914356
TI  - Colonic metastasis after resection of primary squamous cell carcinoma of the
      lung: a case report and literature review.
AB  - Lung cancer is a common malignancy in the world; however symptomatic colonic
      metastasis from primary lung cancer is rare. A 64-year-old man was originally
      found poorly differentiated squamous cell carcinoma of right lung and received
      right lower lobectomy and lymph node dissection. Three years later, the patient
      presented to our emergency room with the symptom of upper abdominal pain and
      weight loss. Abdominal palpation and computed tomography scan of the abdomen
      revealed a large mass measuring 7.6 cm * 8.5 cm in the ascending colon.
      Colonoscopy and biopsy revealed poorly differentiated squamous cell carcinoma
      with similar morphological pattern to that of the previous lung cancer.
      Chemotherapy was given and the patient died 5 mo later. Lung cancer metastatic to
      the colon confers a poor prognosis: overall survival ranged from 5 wk to 1 year,
      with a median survival of 3 mo after the diagnosis of the colonic metastasis. 

PMID- 24914357
TI  - Clinical peer review in the United States: history, legal development and
      subsequent abuse.
AB  - The Joint Commission on Accreditation requires hospitals to conduct peer review
      to retain accreditation. Despite the intended purpose of improving quality
      medical care, the peer review process has suffered several setbacks throughout
      its tenure. In the 1980s, abuse of peer review for personal economic interest led
      to a highly publicized multimillion-dollar verdict by the United States Supreme
      Court against the perpetrating physicians and hospital. The verdict led to
      decreased physician participation for fear of possible litigation. Believing that
      peer review was critical to quality medical care, Congress subsequently enacted
      the Health Care Quality Improvement Act (HCQIA) granting comprehensive legal
      immunity for peer reviewers to increase participation. While serving its intended
      goal, HCQIA has also granted peer reviewers significant immunity likely
      emboldening abuses resulting in Sham Peer Reviews. While legal reform of HCQIA is
      necessary to reduce sham peer reviews, further measures including the need for
      standardization of the peer review process alongside external organizational
      monitoring are critical to improving peer review and reducing the prevalence of
      sham peer reviews. 

PMID- 24914358
TI  - Helicobacter pylori infection in older people.
AB  - Since the discovery of Helicobacter pylori (H. pylori) infection as the major
      cause of gastroduodenal disorders three decades ago, H. pylori has been the focus
      of active research and debate in the scientific community. Its linkage to several
      diseases, such as peptic ulcer disease, gastritis and gastric malignancy is
      incontestable. In particular, it has been noticed that, as the aged population is
      increasing worldwide, older people are at increased risk of developing several
      gastroduodenal diseases and related complications. At the same time, gastric
      cancer is definitely more frequent in elderly than in adult and young people. In
      addition, it has been showed that peptic ulcer and related complications occur
      much more commonly in aged individuals than in young people, resulting in a
      significantly higher mortality. Although this infection plays a crucial role in
      gastrointestinal disorders affecting all age groups and in particular older
      people, only a few studies have been published regarding the latter. This article
      presents an overview of the epidemiology, diagnosis, clinical manifestations and
      therapy of H. pylori infection in elderly people. 

PMID- 24914359
TI  - Helicobacter pylori infection and inflammatory bowel disease: is there a link?
AB  - Helicobacter pylori (H. pylori) infection is one of the most widely spread
      infectious diseases in humans. It can cause chronic gastritis, peptic ulcer
      disease and gastric malignancies and has been associated with extra-gastric
      disorders. H. pylori elicit a chronic systemic inflammatory response which, under
      certain conditions, may trigger autoimmune reactions and may be implicated in the
      pathogenesis of autoimmune diseases. Although the pathogenesis of inflammatory
      bowel disease (IBD) is unknown, it is thought to result from complex interactions
      between environmental factors and microbiota in the gut of individuals who are
      genetically susceptible. Several bacterial and viral agents have been implicated
      in the aetiology of IBD. In theory, H. pylori infection could be involved in the
      pathogenesis of IBD by inducing alterations in gastric and/or intestinal
      permeability or by causing immunological derangements resulting in absorption of
      antigenic material and autoimmunity via various immunological pathways. Similar
      mechanisms may also be responsible for the co-existence of IBD with other
      autoimmune diseases and/or extra-intestinal manifestations. However, the
      epidemiological data fail to support this association. In fact, various studies
      indicate that the prevalence of H. pylori infection is low in patients with IBD,
      suggesting a protective role for this infection in the development of IBD. In
      this report, we aim to shed light on proposed mechanisms and confounding factors
      underlying the potential link between H. pylori infection and IBD. 

PMID- 24914362
TI  - Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric
      carcinogenesis.
AB  - Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy
      and cancer. However, the pathological progression has not been characterized in
      detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are
      unique in that they directly infiltrate into foveolar epithelium aiming the
      proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a
      critical pathogenic step in H. pylori gastritis inducing intensive epithelial
      damage. Epithelial cells carrying accumulated genomic damage and mutations show
      the Malgun (clear) cell change, characterized by large clear nucleus and
      prominent nucleolus. Malgun cells further undergo atypical changes, showing
      nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun
      cell (AMC) change is a novel premalignant condition in high risk gastropathy,
      which may progress and undergo malignant transformation directly. The
      pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new
      diagnosis system of gastritis is proposed based on the critical pathologic steps
      classifying low and high risk gastritis for separate treatment modality. It is
      suggested that the regulation of H. pylori-induced neutrophilic foveolitis might
      be a future therapeutic goal replacing bactericidal antibiotics approach. 

PMID- 24914361
TI  - Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic
      susceptibility and CYP2C19 genotype.
AB  - The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a
      proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin,
      clarithromycin, and metronidazole are mainly influenced by bacterial
      susceptibility to antimicrobial agents and the magnitude of the inhibition of
      acid secretion. Annual cure rates have gradually decreased because of the
      increased prevalence of H. pylori strains resistant to antimicrobial agents,
      especially to clarithromycin. Alternative regimens have therefore been developed
      incorporating different antimicrobial agents. Further, standard PPI therapy
      (twice-daily dosing) often fails to induce a long-term increase in intragastric
      pH > 4.0. Increasing the eradication rate requires more frequent and higher doses
      of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic
      factors such as variants of the genes encoding drug-metabolizing enzymes (e.g.,
      cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance
      protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1beta). For
      example, quadruple daily administration of PPI therapy potently inhibits acid
      secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H.
      pylori eradication regimens that address acid secretion and employ optimal
      antimicrobial agents based on results of antimicrobial agent-susceptibility
      testing may prove effective in attaining higher eradication rates. 

PMID- 24914360
TI  - Helicobacter pylori infection: new pathogenetic and clinical aspects.
AB  - Helicobacter pylori (H. pylori) infects more than half of the world's human
      population, but only 1% to 3% of infected people consequently develop gastric
      adenocarcinomas. The clinical outcome of the infection is determined by host
      genetic predisposition, bacterial virulence factors, and environmental factors.
      The association between H. pylori infection and chronic active gastritis, peptic
      ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid
      tissue lymphoma has been well established. With the exception of unexplained iron
      deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection
      has no proven role in extraintestinal diseases. On the other hand, there is data
      showing that H. pylori infection could be beneficial for some human diseases. The
      unpredictability of the long-term consequences of H. pylori infection and the
      economic challenge in eradicating it is why identification of high-risk
      individuals is crucial. 

PMID- 24914363
TI  - Simple animal model of Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) has become accepted as a human pathogen for the
      development of gastritis and gastroduodenal ulcer. To develop a simple rat model
      of chronic H. pylori infection, male Sprague-Dawley rats were pretreated with
      streptomycin suspended in tap water (5 mg/mL) for 3 d. The rats were inoculated
      by gavage at 1 mL/rat with H. pylori suspension (5 * 10(8)-5 * 10(10) CFU/mL)
      twice daily at an interval of 4 h for three consecutive days. Two weeks after
      inoculation, rats were sacrificed and the stomachs were removed. Antral biopsies
      were performed for urease test and the stomachs were taken for histopathology.
      Successful H. pylori inoculation was defined as a positive urease test and
      histopathology. We reported a 69.8%-83.0% success rate for H. pylori infection
      using the urease test, and hematoxylin and eosin staining confirmed the results.
      Histopathological analysis detected bacteria along the mucous lining of the
      surface epithelium and crypt lumen and demonstrated mild to moderate gastric
      inflammation in successfully inoculated rats. We developed a simple rat model of
      chronic H. pylori infection for research into gastric microcirculatory changes
      and therapy with plant products. 

PMID- 24914364
TI  - Endoscopic therapy for early gastric cancer: standard techniques and recent
      advances in ESD.
AB  - The technique of endoscopic submucosal dissection (ESD) is now a well-known
      endoscopic therapy for early gastric cancer. ESD was introduced to resect large
      specimens of early gastric cancer in a single piece. ESD can provide precision of
      histologic diagnosis and can also reduce the recurrence rate. However, the
      drawback of ESD is its technical difficulty, and, consequently, it is associated
      with a high rate of complications, the need for advanced endoscopic techniques,
      and a lengthy procedure time. Various advances in the devices and techniques used
      for ESD have contributed to overcoming these drawbacks. 

PMID- 24914366
TI  - Epigenetic dysregulation in Epstein-Barr virus-associated gastric carcinoma:
      disease and treatments.
AB  - Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) comprises nearly
      10% of gastric carcinoma cases worldwide. Recently, it was recognised to have
      unique clinicopathologic characteristics, including male predominance, lower
      rates of lymph node involvement, and better prognosis. EBVaGC is further
      characterised by abnormal hypermethylation of tumour suppressor gene promoter
      regions, causing down-regulation of their expression. In the present review, we
      critically discuss the role of EBV in gastric carcinogenesis, summarising the
      role of viral proteins and microRNAs with respect to aberrant methylation in
      EBVaGC. Given the role of epigenetic dysregulation in tumourigenesis, epigenetic
      modifiers may represent a novel therapeutic strategy. 

PMID- 24914365
TI  - Epigenetics: an emerging player in gastric cancer.
AB  - Cancers, like other diseases, arise from gene mutations and/or altered gene
      expression, which eventually cause dysregulation of numerous proteins and
      noncoding RNAs. Changes in gene expression, i.e., upregulation of oncogenes
      and/or downregulation of tumor suppressor genes, can be generated not only by
      genetic and environmental factors but also by epigenetic factors, which are
      inheritable but nongenetic modifications of cellular chromosome components.
      Identification of the factors that contribute to individual cancers is a
      prerequisite to a full understanding of cancer mechanisms and the development of
      customized cancer therapies. The search for genetic and environmental factors has
      a long history in cancer research, but epigenetic factors only recently began to
      be associated with cancer formation, progression, and metastasis. Epigenetic
      alterations of chromatin include DNA methylation and histone modifications, which
      can affect gene-expression profiles. Recent studies have revealed diverse
      mechanisms by which chromatin modifiers, including writers, erasers and readers
      of the aforementioned modifications, contribute to the formation and progression
      of cancer. Furthermore, functional RNAs, such as microRNAs and long noncoding
      RNAs, have also been identified as key players in these processes. This review
      highlights recent findings concerning the epigenetic alterations associated with
      cancers, especially gastric cancer. 

PMID- 24914367
TI  - Virus-related liver cirrhosis: molecular basis and therapeutic options.
AB  - Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV)
      are the major causes of cirrhosis globally. It takes 10-20 years to progress from
      viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused
      by the infections contributes to the inflammation-necrosis-regeneration process,
      ultimately cirrhosis. CD8(+) T cells and NK cells cause liver damage via
      targeting the infected hepatocytes directly and releasing pro-inflammatory
      cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis
      via secreting fibrosis-related factors. Under the inflammatory microenvironment,
      the viruses experience mutation-selection-adaptation to evade immune clearance.
      However, immune selection of some HBV mutations in the evolution towards
      cirrhosis seems different from that towards hepatocellular carcinoma. As viral
      replication is an important driving force of cirrhosis pathogenesis, antiviral
      treatment with nucleos(t)ide analogs is generally effective in halting the
      progression of cirrhosis, improving liver function and reducing the morbidity of
      decompensated cirrhosis caused by chronic HBV infection. Interferon-alpha plus
      ribavirin and/or the direct acting antivirals such as Vaniprevir are effective
      for compensated cirrhosis caused by chronic HCV infection. The standard of care
      for the treatment of HCV-related cirrhosis with interferon-alpha plus ribavirin
      should consider the genotypes of IL-28B. Understanding the mechanism of
      fibrogenesis and hepatocyte regeneration will facilitate the development of novel
      therapies for decompensated cirrhosis. 

PMID- 24914368
TI  - Selection of a TIPS stent for management of portal hypertension in liver
      cirrhosis: an evidence-based review.
AB  - Nowadays, transjugular intrahepatic portosystemic shunt (TIPS) has become a
      mainstay treatment option for the management of portal hypertension-related
      complications in liver cirrhosis. Accumulated evidence has shown that its
      indications are being gradually expanded. Notwithstanding, less attention has
      been paid for the selection of an appropriate stent during a TIPS procedure.
      Herein, we attempt to review the current evidence regarding the diameter, type,
      brand, and position of TIPS stents. Several following recommendations may be
      considered in the clinical practice: (1) a 10-mm stent may be more effective than
      an 8-mm stent for the management of portal hypertension, and may be superior to a
      12-mm stent for the improvement of survival and shunt patency; (2) covered stents
      are superior to bare stents for reducing the development of shunt dysfunction;
      (3) if available, Viatorr stent-grafts may be recommended due to a higher rate of
      shunt patency; and (4) the placement of a TIPS stent in the left portal vein
      branch may be more reasonable for decreasing the development of hepatic
      encephalopathy. However, given relatively low quality of evidence, prospective
      well-designed studies should be warranted to further confirm these
      recommendations. 

PMID- 24914369
TI  - Historical overview and review of current day treatment in the management of
      acute variceal haemorrhage.
AB  - Variceal haemorrhage is one of the most devastating consequences of portal
      hypertension, with a 1-year mortality of 40%. With the passage of time, acute
      management strategies have developed with improved survival. The major historical
      treatment landmarks in the management of variceal haemorrhage can be divided into
      surgical, medical, endoscopic and radiological breakthroughs. We sought to
      provide a historical overview of the management of variceal haemorrhage and how
      treatment modalities over time have impacted on clinical outcomes. A PubMed
      search of the following terms: portal hypertension, variceal haemorrhage, gastric
      varices, oesophageal varices, transjugular intrahepatic portosystemic shunt was
      performed. To complement this, GoogleTM was searched with the aforementioned
      terms. Other relevant references were identified after review of the reference
      lists of articles. The review of therapeutic advances was conducted divided into
      pre-1970s, 1970/80s, 1990s, 2000-2010 and post-2010. Also, a summary and review
      on the pathophysiology of portal hypertension and clinical outcomes in variceal
      haemorrhage was performed. Aided by the development of endoscopic therapies,
      medication and improved radiological interventions; the management of variceal
      haemorrhage has changed over recent decades with improved survival from an often
      terminating event in recent past. 

PMID- 24914370
TI  - Involvement of heat shock proteins in gluten-sensitive enteropathy.
AB  - Gluten-sensitive enteropathy, also known as coeliac disease (CD), is an
      autoimmune disorder occurring in genetically susceptible individuals that damages
      the small intestine and interferes with the absorption of other nutrients. As it
      is triggered by dietary gluten and related prolamins present in wheat, rye and
      barley, the accepted treatment for CD is a strict gluten-free diet. However, a
      complete exclusion of gluten-containing cereals from the diet is often difficult,
      and new therapeutic strategies are urgently needed. A class of proteins that have
      already emerged as drug targets for other autoimmune diseases are the heat shock
      proteins (HSPs), which are highly conserved stress-induced chaperones that
      protect cells against harmful extracellular factors. HSPs are expressed in
      several tissues, including the gastrointestinal tract, and their levels are
      significantly increased under stress circumstances. HSPs exert immunomodulatory
      effects, and also play a crucial role in the maintenance of epithelial cell
      structure and function, as they are responsible for adequate protein folding,
      influence the degradation of proteins and cell repair processes after damage, and
      modulate cell signalling, cell proliferation and apoptosis. The present review
      discusses the involvement of HSPs in the pathophysiology of CD. Furthermore, HSPs
      may represent a useful therapeutic target for the treatment of CD due to the
      cytoprotective, immunomodulatory, and anti-apoptotic effects in the intestinal
      mucosal barrier. 

PMID- 24914371
TI  - Treatment of refractory diabetic gastroparesis: Western medicine and traditional
      Chinese medicine therapies.
AB  - Refractory diabetic gastroparesis (DGP), a disorder that occurs in both type 1
      and type 2 diabetics, is associated with severe symptoms, such as nausea and
      vomiting, and results in an economic burden on the health care system. In this
      article, the basic characteristics of refractory DGP are reviewed, followed by a
      discussion of therapeutic modalities, which encompasses the definitions and
      clinical manifestations, pathogenesis, diagnosis, and therapeutic efficacy
      evaluation of refractory DGP. The diagnostic standards assumed in this study are
      those set forth in the published literature due to the absence of recognized
      diagnosis criteria that have been assessed by an international organization. The
      therapeutic modalities for refractory DGP are as follows: drug therapy,
      nutritional support, gastric electrical stimulation, pyloric botulinum toxin
      injection, endoscopic or surgical therapy, and traditional Chinese treatment. The
      therapeutic modalities may be used alone or in combination. The use of
      traditional Chinese treatments is prevalent in China. The effectiveness of these
      therapies appears to be supported by preliminary evidence and clinical
      experience, although the mechanisms that underlie these effects will require
      further research. The purpose of this article is to explore the potential of
      combined Western and traditional Chinese medicine treatment methods for improved
      patient outcomes in refractory DGP. 

PMID- 24914372
TI  - miR-132 inhibits colorectal cancer invasion and metastasis via directly targeting
      ZEB2.
AB  - AIM: To investigate the biological role and underlying mechanism of miR-132 in
      colorectal cancer (CRC) progression and invasion. METHODS: Quantitative RT-PCR
      analysis was used to examine the expression levels of miR-132 in five CRC cell
      lines (SW480, SW620, HCT116, HT29 and LoVo) and a normal colonic cell line
      NCM460, as well as in tumor tissues with or without metastases. The Kaplan-Meier
      method was used to analyze the prognostic significance of miR-132 in CRC
      patients. The biological effects of miR-132 were assessed in CRC cell lines using
      the transwell assay. Quantitative RT-PCR and western blot analyses were employed
      to evaluate the expression of miR-132 targets. The regulation of ZEB2 by miR-132
      was confirmed using the luciferase activity assay. RESULTS: miR-132 was
      significantly down-regulated in the CRC cell lines compared with the normal
      colonic cell line (P < 0.05), as well as in the CRC tissues with distant
      metastases compared with the tissues without metastases (10.52 +/- 4.69 vs 23.11
      +/- 7.84) (P < 0.001). Down-regulation of miR-132 was associated with tumor size
      (P = 0.016), distant metastasis (P = 0.002), and TNM stage (P = 0.020) in CRC
      patients. Kaplan-Meier survival curve analysis indicated that patients with low
      expression of miR-132 tended to have worse disease-free survival than patients
      with high expression of miR-132 (P < 0.001). Moreover, ectopic expression of miR
      132 markedly inhibited cell invasion (P < 0.05) and the epithelial-mesenchymal
      transition (EMT) in CRC cell lines. Further investigation revealed ZEB2, an EMT
      regulator, was a downstream target of miR-132. CONCLUSION: Our study indicated
      that miR-132 plays an important role in the invasion and metastasis of CRC.

PMID- 24914373
TI  - IGFBPrP1 induces liver fibrosis by inducing hepatic stellate cell activation and
      hepatocyte apoptosis via Smad2/3 signaling.
AB  - AIM: To investigate the role and mechanism of insulin-like growth factor binding
      protein-related protein 1 (IGFBPrP1) in the development of liver fibrosis.
      METHODS: An in vitro model using hepatic stellate cell (HSC)-T6 cells and an in
      vivo model of rat liver overexpressing IGFBPrP1 were established using an
      IGFBPrP1-expressing recombinant adenovirus. The expression of IGFBPrP1 was
      examined by immunofluorescence, and the expression of collagen I and fibronectin
      was measured by real-time reverse transcription-polymerase chain reaction and
      Western blot analysis. The expression of Smad2/3 and p-Smad2/3 was examined by
      Western blot and immunohistochemistry. A shSmad3-expressing recombinant
      adenovirus (AdshSmad3) was designed and used to knockdown the Smad3 gene in HSC
      T6 cells and rat liver fibrosis transfected with IGFBPrP1. The expression of
      collagen I, fibronectin, and alpha-smooth muscle actin (alpha-SMA) was determined
      by Western blot analysis and immunohistochemistry. Hepatocyte apoptosis was
      assessed using TUNEL assay. RESULTS: IGFBPrP1 overexpression induced collagen
      deposition and up-regulated the expression of alpha-SMA and p-Smad2/3, and
      AdshSmad3 inhibited IGFBPrP1-stimulated p-Smad2/3 activation and the expression
      of alpha-SMA, collagen I and fibronectin in HSC-T6 cells. Similarly, increased
      hepatocyte apoptosis (38.56% +/- 3.42% vs 0.24% +/- 0.03%, P < 0.05), alpha-SMA
      positive stained cells (29.84% +/- 1.36% vs 5.83% +/- 1.47%, P < 0.05), and
      increased numbers of Smad3 (35.88% +/- 2.15% vs 10.24% +/- 1.31%, P < 0.05) and p
      Smad2/3 positive cells (28.87% +/- 2.73% vs 8.23% +/- 0.98%, P < 0.05) were
      detected in the livers of IGFBPrP1-overexpressing rats compared with the control
      group. Moreover, AdshSmad3 reduced IGFBPrP1-stimulated Smad3 expression and
      attenuated alpha-SMA expression (29.84% +/- 1.36% vs 8.23% +/- 1.28%, P < 0.05),
      hepatocyte apoptosis (38.56% +/- 3.42% vs 6.75% +/- 0.52%, P < 0.05), and both
      collagen I and fibronectin deposition in the livers of AdIGFBPrP1-treated rats.
      CONCLUSION: IGFBPrP1 induces liver fibrosis by mediating the activation of
      hepatic stellate cells and hepatocyte apoptosis in a Smad3-dependent mechanism.

PMID- 24914374
TI  - Changes in iron transporter divalent metal transporter 1 in proximal jejunum
      after gastric bypass.
AB  - AIM: To describe the variation that divalent metal transporter 1 (DMT1) shows in
      patients after Roux-en-Y gastric bypass (RYGB) surgery. METHODS: Prospective and
      analytical study of DMT1 level at the brush border of proximal jejunum in
      patients having undergone RYGB surgery. The mucosa of proximal jejunum forming
      the gastrojejunal anastomosis was biopsied during surgery and after 6 mo later
      with an endoscopic biopsy. All the patients received precise instructions
      regarding feeding and nutritional supplementation. Both samples were processed at
      the same time by immunohistochemistry and western blot. Samples were analysed by
      a pathologist. For statistical analysis, the chi(2) and Wilcoxon tests were used.
      RESULTS: Sixteen patients were recruited, 13 of whom completed the study. Twelve
      were women. Average age and body mass index (BMI) were 44.1 and 40.4,
      respectively. Both body weight and BMI decreased significantly during the study
      period, with an average percent excess weight loss (%EWL) of 60% +/- 13.3% and an
      average percent excess BMI loss (%EBMIL) of 79.6% +/- 21.6%. Only two patients
      presented with mild anaemia 6 mo after surgery, but their ferritin levels stayed
      within normal ranges. Staining for DMT1 showed a significant increase in the
      cytoplasm of enterocytes located at the tips of the villi (chi(2) = 6.03; P =
      0.049). Nevertheless, the total quantity of DMT1 decreased significantly (Z =
      2.04; P = 0.04). Associated with these results, we observed a significant
      increase in goblet cells in the villi 6 mo postoperatively (Z = -2.47; P =
      0.013). CONCLUSION: Six months after RYGB surgery, patients exhibit an increase
      in DMT1 expression in the enterocytes of the tips of the villi at the proximal
      jejunum.

PMID- 24914375
TI  - Effects of bile acids on cyclooxygenase-2 expression in a rat model of
      duodenoesophageal anastomosis.
AB  - AIM: To examine the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2
      (PGE2) in rat esophageal lesions induced by reflux of duodenal contents. METHODS:
      Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal
      reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total
      gastrectomy to elicit chronic esophagitis. In ten rats sham operations with only
      a midline laparotomy were performed (Control). The rats were sacrificed at the
      40(th) week, their esophagi were taken for hematoxylin and eosin staining and for
      examination of expression of COX2, PGE2, and proliferating cell nuclear antigen
      (PCNA), and total bile acids in the esophageal lumen was measured. RESULTS: After
      40 wk of reflux, columnar dysplasia, squamous cell carcinoma and adenocarcinoma
      were observed. Total bile acids in the esophageal lumen were significantly
      increased in the EDA group compared with the sham operated rats. PCNA labelling
      index and esophageal tissue PGE2 levels were higher in dysplastic and cancer
      tissues than in control tissues. Overexpression of COX2 was observed in
      dysplastic and cancer tissues. CONCLUSION: Reflux of duodenal contents induces
      COX2 expression and increases prostaglandin synthesis in dysplastic and cancer
      tissues. This result suggests a possible mechanism by which bile acids promote
      esophageal cancer.

PMID- 24914376
TI  - Dual-priming oligonucleotide-based multiplex PCR using tissue samples in rapid
      urease test in the detection of Helicobacter pylori infection.
AB  - AIM: To investigate whether tissue samples processed by the rapid urease test
      (RUT) kit are suitable for dual-priming oligonucleotide-based multiplex
      polymerase chain reaction (DPO-PCR) to detect Helicobacter pylori (H. pylori).
      METHODS: A total of 54 patients with specific gastrointestinal symptom were
      enrolled in this study. During endoscopy, gastric biopsy specimens were taken for
      histology, RUT, and DPO-PCR. DPO-PCR was performed on gastric biopsy samples and
      tissue samples that were analyzed by RUT at 2 separate institutes. In detecting
      H. pylori, the concordance rate of the DPO-PCR tests between the tissue samples
      that had been submitted to RUT and the gastric biopsy samples was investigated.
      RESULTS: H. pylori co-occurred with 76.0% (19/25) of gastric ulcers, 64.3% (9/14)
      of duodenal ulcers, and 33.3% (4/12) of gastritis cases. H. pylori infection was
      found in 100% (3/3) of the patients with both gastric and duodenal ulcers.
      Overall, H. pylori was detected in 35 of 54 (64.8%) patients. The diagnostic
      sensitivities of histology, RUT, and DPO-PCR were 85.7% (30/35), 74.3% (26/35),
      and 97.1% (34/35), respectively (P = 0.02). The positive predictive value (PPV)
      of DPO-PCR was 94.4%, whereas the negative predictive value (NPV) was 94.7%. In
      the rapid urease test (CLOtest)-negative cases, the frequency of positive DPO-PCR
      and histologic results was 20.0% (7/35). The concordance rate of the DPO-PCR
      tests between the tissue samples from the RUT kit and the gastric biopsy samples
      was 94.4% (51/54). The rate of DPO-PCR and silver stain positivity in the RUT
      negative cases was 20.0% (7/35). CONCLUSION: In diagnosing H. pylori infection,
      DPO-PCR can be performed on tissue samples that have been processed by the RUT
      kit. Particularly, in patients with RUT-negative results, DPO-PCR on these tissue
      samples could be helpful in detecting of H. pylori infection.

PMID- 24914377
TI  - Investigation of cholecystokinin receptors in the human lower esophageal
      sphincter.
AB  - AIM: To compare the binding of cholecystokinin (CCK)-8 to CCK receptors in sling
      and clasp fibers of the human lower esophageal sphincter. METHODS: Esophageal
      sling and clasp fibers were isolated from eight esophagectomy specimens, resected
      for squamous cell carcinoma in the upper two thirds of the esophagus, which had
      been maintained in oxygenated Kreb's solution. Western blot was used to measure
      CCK-A and CCK-B receptor subtypes in the two muscles. A radioligand binding assay
      was used to determine the binding parameters of (3)H-CCK-8S to the CCK receptor
      subtypes. The specificity of binding was determined by the addition of
      proglumide, which blocks the binding of CCK to both receptor subtypes. RESULTS:
      There was no significant difference between the sling and clasp fibers of the
      human lower esophageal sphincter in the amount of CCK-A [integrated optical
      density (IOD) value: 22.65 +/- 0.642 vs 22.328 +/- 1.042, P = 0.806] or CCK-B
      receptor protein (IOD value: 13.20 +/- 0.423 vs 12.45 +/- 0.294, P = 0.224) as
      measured by Western blot. The maximum binding of radio-labeled CCK-8S was higher
      in the sling fibers than in the clasp fibers (595.75 +/- 3.231 cpm vs 500.000 +/-
      10.087 cpm, P < 0.001) and dissociation constant was lower (K(d): 1.437 +/- 0.024
      nmol/L vs 1.671 +/- 0.024 nmol/L, P < 0.001). The IC50 of the receptor specific
      antagonists were lower for the CCK-A receptors than for the CCK-B (P < 0.01).
      CONCLUSION: CCK binding modulates the contractile function of the lower
      esophageal sphincter through differential binding to the CCK-A receptor on the
      sling and clasp fibers.

PMID- 24914378
TI  - Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell
      proliferation.
AB  - AIM: To provide further insight into the characterization of mucosa-associated
      Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients.
      METHODS: Phylogroups and the presence of cyclomodulin-encoding genes of mucosa
      associated E. coli from colon cancer and diverticulosis specimens were determined
      by PCR. Adhesion and invasion experiments were performed with I-407 intestinal
      epithelial cells using gentamicin protection assay. Carcinoembryonic antigen
      related cell adhesion molecule 6 (CEACAM6) expression in T84 intestinal
      epithelial cells was measured by enzyme-linked immunosorbent assay and by Western
      Blot. Gut colonization, inflammation and pro-carcinogenic potential were assessed
      in a chronic infection model using CEABAC10 transgenic mice. Cell proliferation
      was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry
      staining of Ki67. RESULTS: Analysis of mucosa-associated E. coli from colon
      cancer and diverticulosis specimens showed that whatever the origin of the E.
      coli strains, 86% of cyclomodulin-positive E. coli belonged to B2 phylogroup and
      most harbored polyketide synthase (pks) island, which encodes colibactin, and/or
      cytotoxic necrotizing factor (cnf) genes. In vitro assays using I-407 intestinal
      epithelial cells revealed that mucosa-associated B2 E. coli strains were poorly
      adherent and invasive. However, mucosa-associated B2 E. coli similarly to Crohn's
      disease-associated E. coli are able to induce CEACAM6 expression in T84
      intestinal epithelial cells. In addition, in vivo experiments using a chronic
      infection model of CEACAM6 expressing mice showed that B2 E. coli strain 11G5
      isolated from colon cancer is able to highly persist in the gut, and to induce
      colon inflammation, epithelial damages and cell proliferation. CONCLUSION: In
      conclusion, these data bring new insights into the ability of E. coli isolated
      from patients with colon cancer to establish persistent colonization, exacerbate
      inflammation and trigger carcinogenesis.

PMID- 24914379
TI  - Role of cystatin C and renal resistive index in assessment of renal function in
      patients with liver cirrhosis.
AB  - AIM: To evaluate the clinical significance of cystatin C and renal resistive
      index for the determination of renal function in patients with liver cirrhosis.
      METHODS: We conducted a study of 63 patients with liver cirrhosis. A control
      group comprised of 30 age and gender-matched healthy persons. Serum cystatin C
      was determined in all study subjects and renal Doppler ultrasonography was made.
      Estimated glomerular filtration rate from serum creatinine (GFRCr) and cystatin C
      (GFRCys) was calculated. RESULTS: We confirmed significant differences in values
      of cystatin C between patients with different stages of liver cirrhosis according
      to Child-Pugh (P = 0.01), and a significant correlation with model of end stage
      liver disease (MELD) score (r s = 0.527, P < 0.001). More patients with decreased
      glomerular filtration rate were identified based on GFRCys than on GFRCr (P <
      0.001). Significantly higher renal resistive index was noted in Child-Pugh C than
      in A (P < 0.001) and B stage (P = 0.001). Also, a significant correlation between
      renal resistive index and MELD score was observed (r s = 0.607, P < 0.001). Renal
      resistive index correlated significantly with cystatin C (r s = 0.283, P = 0.028)
      and showed a negative correlation with GFRCys (r s = -0.31, P = 0.016).
      CONCLUSION: Cystatin C may be a more reliable marker for assessment of liver
      insufficiency. Additionally, cystatin C and renal resistive index represent
      sensitive indicators of renal dysfunction in patients with liver cirrhosis.

PMID- 24914380
TI  - Prognostic factors in stage IB gastric cancer.
AB  - AIM: To identify the subset of patients with stage IB gastric cancer with an
      unfavorable prognosis. METHODS: Overall survival (OS) rates were examined in 103
      patients with stage IB (T1N1M0 and T2N0M0) gastric cancer between January 2000
      and December 2011. Univariate and multivariate analyses were performed to
      identify risk factors using a Cox proportional hazards model. RESULTS: The OS
      rates of patients with T1N1 and T2N0 cancer were 89.2% and 94.1% at 5-years,
      respectively. Both univariate and multivariate analyses demonstrated that tumor
      location was the only significant prognostic factor. The OS rate was 81.8% at 5
      years when the tumor was located in the upper third of the stomach and was 95.5%
      at 5-years when the tumor was located in the middle or lower third of the stomach
      (P = 0.0093). CONCLUSION: These data may suggest that tumor location is
      associated with survival in patients with stage IB gastric cancer.

PMID- 24914381
TI  - Conventional endoscopic features are not sufficient to differentiate small, early
      colorectal cancer.
AB  - AIM: To evaluate the depth of invasion of small, early colorectal cancers (ECCs)
      using conventional endoscopic features. METHODS: From January 2005 to September
      2011, colonoscopy cohort showed that a total of 72 patients with small colorectal
      cancers with the size less than 20 mm underwent colonoscopy at the Yonsei
      University College of Medicine, Seoul, South Korea. Among them, 8 patients were
      excluded due to incomplete medical records. Finally, a total of 64 ECCs with
      submucosa (SM) invasion and size less than 20 mm were included. One hundred fifty
      two adenomas with size less than 20 mm were included as controls. Nine endoscopic
      features, including seven morphological findings (i.e., loss of lobulation,
      excavation, demarcated and depressed areas, stalk swelling, fullness, fold
      convergence, and bleeding ulcers), pit patterns, and non-lifting signs, were
      evaluated retrospectively. All endoscopic features were evaluated by two
      experienced endoscopists who have each performed over 1000 colonoscopies annually
      for more than five years without knowledge of the histology. RESULTS: Among the
      morphological findings, the size of deep submucosal cancers was bigger than that
      of superficial lesions (16.9 mm vs 12.3 mm, P < 0.001). Also, demarcated
      depressed areas, stalk swelling, and fullness were more common in deep SM cancers
      than in superficial tumors (demarcated depressed areas: 52.0% vs 15.7%, P <
      0.001; stalk swelling: 100% vs 4.2%, P < 0.001; fullness: 25.0% vs 0%, P =
      0.001). Among deep SM cancers, 96% of polyps showed invasive pit patterns,
      whereas 19.4% of superficial tumors showed invasive pit patterns (P < 0.001). A
      positive non-lifting sign was more common in deep SM cancers (85.0% vs 28.6%, P <
      0.001). Diagnostic accuracy of invasive morphology, invasive pit patterns, and
      non-lifting signs for deep SM cancers were 71%, 82%, and 75%, respectively.
      CONCLUSION: Conventional endoscopic findings were insufficient to discriminate
      small, deep SM cancers from superficial SM cancers by white light, standard
      colonoscopy.

PMID- 24914382
TI  - Inflammatory markers as selection criteria of hepatocellular carcinoma in living
      donor liver transplantation.
AB  - AIM: To investigate that inflammatory markers can predict accurately the
      prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver
      transplantation (LDLT). METHODS: From October 2000 to November 2011, 224 patients
      who underwent living donor liver transplantation for HCC at our institution were
      enrolled in this study. We analyzed disease-free survival (DFS) and overall
      survival (OS) after LT in patients with HCC and designed a new score model using
      pretransplant neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP).
      RESULTS: The DFS and OS in patients with an NLR level >= 6.0 or CRP level >= 1.0
      were significantly worse than those of patients with an NLR level < 6.0 or CRP
      level < 1.0 (P = 0.049, P = 0.003 for NLR and P = 0.010, P < 0.001 for CRP,
      respectively). Using a new score model using the pretransplant NLR and CRP, we
      can differentiate HCC patients beyond the Milan criteria with a good prognosis
      from those with a poor prognosis. CONCLUSION: Combined with the Milan criteria,
      new score model using NLR and CRP represent new selection criteria for LDLT
      candidates with HCC, especially beyond the Milan criteria.

PMID- 24914383
TI  - Hematologic diseases: high risk of Clostridium difficile associated diarrhea.
AB  - AIM: To investigate the incidence and clinical outcome of Clostridium difficile
      (C. difficile) associated diarrhea (CDAD) in patients with hematologic disease.
      METHODS: We retrospectively reviewed the medical records of patients who
      underwent C. difficile testing in a tertiary hospital in 2011. The incidence and
      risk factors for CDAD and its clinical course including recurrence and mortality
      were assessed in patients with hematologic disease and compared with those in
      patients with nonhematologic disease. RESULTS: About 320 patients were diagnosed
      with CDAD (144 patients with hematologic disease; 176 with nonhematologic
      disease). The incidence of CDAD in patients with hematologic disease was
      estimated to be 36.7 cases/10000 patient hospital days, which was higher than the
      5.4 cases/10000 patient hospital days in patients with nonhematologic disease.
      Recurrence of CDAD was more frequent in patients with hematologic disease
      compared to those with nonhematologic disease (18.8% vs 8.5%, P < 0.01), which
      was associated with higher re-use of causative antibiotics for CDAD. Mortality
      due to CDAD did not differ between the two groups. Multivariate analysis showed
      that intravenous immunoglobulin was the only significant factor associated with a
      lower rate of recurrence of CDAD in patients with hematologic disease.
      CONCLUSION: The incidence and recurrence of CDAD was higher in patients with
      hematologic disease than in those with nonhematologic disease.

PMID- 24914384
TI  - Value of 18F-FDG PET-CT in surveillance of postoperative colorectal cancer
      patients with various carcinoembryonic antigen concentrations.
AB  - AIM: To evaluate the value of positron emission tomography (PET)/computerized
      tomography (CT) in surveillance of colorectal cancer (CRC) patients with
      different carcinoembryonic antigen (CEA) concentrations. METHODS: One hundred and
      six postoperative CRC patients who had suspected recurrence or metastasis and
      received fluorodeoxyglucose (FDG) PET/CT within one week were included in this
      study. The final diagnosis was confirmed by histological examination or clinical
      follow-up over at least six months. RESULTS: The sensitivity, specificity, and
      accuracy of FDG PET/CT were 95.2%, 82.6%, and 92.5%, and 94.8%, 81.4% and 92.8%,
      respectively, in the case- and lesion-based analyses. The sensitivity and
      accuracy of FDG PET/CT significantly differed from CT in both analyses (chi(2) =
      8.186, P = 0.004; chi(2) =6.201, P = 0.013; chi(2) =13.445, P = 0.000; chi(2)
      =11.194, P = 0.001). In the lesion-based analysis, the sensitivity, specificity,
      and accuracy of FDG PET/CT in the abnormal CEA group were 97.8%, 82.6%, and
      95.6%, compared with 81.3%, 80%, and 80.6% for patients with normal CEA levels.
      In case-based analysis, the sensitivity, specificity, and accuracy of FDG PET/CT
      were 97.2%, 77.8%, and 95% in abnormal CEA group. Only in lesion-based analysis,
      the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were
      significantly superior to those in the normal CEA group (chi(2) =6.432, P =
      0.011; chi(2) =7.837, P = 0.005). FDG PET/CT changed the management in 45.8% of
      patients with positive scans. CONCLUSION: FDG PET/CT showed superior diagnostic
      value and is an advisable option in surveillance of postoperative CRC patients
      with a vague diagnosis.

PMID- 24914385
TI  - Telomerase and hTERT: can they serve as markers for gastric cancer diagnosis?
AB  - AIM: To investigate telomerase activity and human telomerase reverse
      transcriptase (hTERT) expression in normal human gastric mucosal epithelial cells
      (nhGMECs) and fibroblasts (nhGMFs). METHODS: nhGMECs and nhGMFs were isolated and
      cultured from specimens obtained during routine surgery for bleeding peptic
      ulcer. Telomerase activity in nhGMFs, nhGMECs, and the tumor cell lines BGC-823,
      SGC-7901 and MKN-28 cells was analyzed using the telomeric repeat amplification
      protocol assay. hTERT protein was determined in nhGMECs, nhGMFs, BGC-823, SGC
      7901 and MKN-28 cells by indirect immunofluorescence. RESULTS: A similar level of
      telomerase activity was observed in nhGMECs, nhGMFs and BGC-823, SGC-7901, MKN-28
      cell lines. Positive hTERT immunostaining was detected in nhGMECs, nhGMFs, BGC
      823, SGC-7901 and MKN-28 cell lines. CONCLUSION: The use of telomerase or hTERT
      as diagnostic markers for gastric cancer may require further studies.

PMID- 24914386
TI  - Liver resection in hepatitis B related-hepatocellular carcinoma: clinical
      outcomes and safety in elderly patients.
AB  - AIM: To compare the morbidity and mortality in young and elderly hepatocellular
      carcinoma (HCC) patients undergoing liver resection. METHODS: We retrospectively
      enrolled 1543 consecutive hepatitis B (HBV)-related HCC patients undergoing
      elective hepatic resection in our cohort, including 207 elderly patients (>= 65
      years) and 1336 younger patients (< 65 years). Patient characteristics and
      clinical outcomes after liver resection were compared between the two groups.
      RESULTS: Elderly patients had more preoperative comorbidities and lower alanine
      aminotransferase and aspartate aminotransferase levels. Positive rates for
      hepatitis B surface antigen (P < 0.001), hepatitis B e antigen (P < 0.001) and
      HBV DNA (P = 0.017) were more common in younger patients. Overall complications
      and their severity classified using the Clavien system were similar in the two
      groups (33.3% vs 29.6%, P = 0.271). Elderly patients had a higher rate of
      postoperative cardiovascular complications (3.9% vs 0.6%, P = 0.001),
      neurological complications (2.9% vs 0.4%, P < 0.001) and mortality (3.4% vs 1.2%,
      P = 0.035), and had more hospital stay requirement (13 d vs 12 d , P < 0.001) and
      more intensive care unit stay (36.7% vs 27.8%, P = 0.008) compared with younger
      patients. However, postoperative hepatic insufficiency was more common in the
      younger group (7.7% vs 3.4%, P = 0.024). CONCLUSION: Hepatectomy can be safely
      performed in elderly patients. Age should not be regarded as a contraindication
      to liver resection with expected higher complication and mortality rates.

PMID- 24914387
TI  - Controlled attenuation parameter for evaluating liver steatosis in chronic viral
      hepatitis.
AB  - AIM: To assess the performance of controlled attenuation parameter (CAP) in
      patients with chronic viral hepatitis. METHODS: CAP is a new technique that
      measures the attenuation in the liver of an ultrasound beam, which is directly
      related to lipid accumulation. Consecutive patients undergoing liver biopsy for
      chronic viral hepatitis were studied using the M probe of FibroScan device
      (Echosens, Paris, France). The device estimates liver steatosis in decibel per
      meter (dB/m). An expert operator performed all measurements. Steatosis was graded
      according to Kleiner's classification. Pearson or Spearman rank coefficient was
      used to test correlation between two study variables. Linear regression was used
      for multivariate model to assess the association between CAP and other variables.
      Receiver operating characteristic curve analysis was performed to calculate area
      under the curve (AUROC) for S0 vs S1-S3 and S0-S1 vs S2-S3. RESULTS: 115 subjects
      (85 males and 30 females) were prospectively studied. The mean values of CAP were
      227.1 +/- 43.1 for S0; 254.6 +/- 38.9 for S1; 297.8 +/- 49.4 dB/m for S2-S3. In
      univariate analysis CAP showed a significant correlation with age, body mass
      index (BMI), degree of steatosis, and cholesterol. Multivariate regression
      analysis confirmed the correlation with the degree of steatosis [coefficient, 1.2
      (0.60-1.83); P < 10(-5)] and BMI [coefficient, 4.1 (0.5-7.8); P = 0.03] but not
      with all other variables. Optimal cutoff values for S >= 1 and S >= 2 were 219
      dB/m [AUROC, 0.76 (0.67-0.84); sensitivity, 91.1% (78.8-97.5); specificity, 51.6%
      (38.7-64.2); positive predictive value, 56.9% (44.7-68.6); negative predictive
      value, 89.2% (74.3-97.0); positive likelihood ratio, 1.88 (1.4-2.5); negative
      likelihood ratio, 0.17 (0.07-0.5)] and 296 dB/m [AUROC, 0.82 (0.74-0.89);
      sensitivity, 60.0% (32.3-83.7); specificity, 91.5% (83.9-96.3); positive
      predictive value, 52.9% (27.8-77.0); negative predictive value, 93.5% (86.3
      97.6); positive likelihood ratio, 7.05 (3.2-15.4); negative likelihood ratio,
      0.44 (0.2-0.8)], respectively. CONCLUSION: Controlled attenuation parameter could
      be a useful tool in the clinical management of patients with chronic viral
      hepatitis for detecting liver steatosis.

PMID- 24914388
TI  - Potential role of human papilloma virus in the pathogenesis of gastric cancer.
AB  - AIM: To demonstrate the presence and biological activity of human papilloma virus
      (HPV) in gastric cancer (GAC) tissues. METHODS: The study involved 84 surgically
      treated patients with gastric adenocarcinoma, regardless of the clinical stage of
      the disease. The presence of HPV DNA of high oncogenic risk types in formalin
      fixed, paraffin-embedded tumor samples was determined using quantitative
      polymerase chain reaction analysis. A stringent protocol of prevention of cross-
      and environmental contamination was applied during DNA isolation, and
      amplification, as well as confirmation of the biological activity of the virus in
      tumor cells, was implemented. The study utilized the Real-time High Risk HPV
      test, which detects the DNA of 14 HPV subtypes that are considered to have high
      oncogenic potential. The overexpression of the p16(INK4a) protein assessed
      immunohistochemically was considered confirmation of the HPV infection. RESULTS:
      Among the 89 patients initially included in the study group, diagnostic results
      were obtained for 84 individuals. In five cases, either the histopathological
      material was too scant to isolate the necessary amount of DNA, or the isolated
      DNA was significantly degraded, resulting in the failure of internal control
      amplification within the predefined number of 35 cycles. Those patients were
      excluded from further analysis. The amplification of HPV DNA was demonstrated in
      none of the 84 tissue samples; thus, all cases were considered to have a negative
      DNA status of highly oncogenic HPV subtypes. Immunohistochemical staining
      provided diagnostic results for all of the examined tissue samples, and excluded
      the accumulation of the p16(INK4a) protein in tumor cells, thus confirming the
      lack of active HPV infection in all of the individuals. CONCLUSION: The study
      does not confirm the presence or biological activity of HPV in tumor tissues.
      Thus, the relationship between GAC and HPV infection, in the Central European
      population seems doubtful.

PMID- 24914389
TI  - Protocol liver biopsy is the only examination that can detect mid-term graft
      fibrosis after pediatric liver transplantation.
AB  - AIM: To assessed the clinical significance of protocol liver biopsy (PLB) in
      pediatric liver transplantation (LT). METHODS: Between July 2008 and August 2012,
      89 and 55 PLBs were performed in pediatric patients at two and five years after
      LT, respectively. We assessed the histopathological findings using the Metavir
      scoring system, including activity (A) and fibrosis (F), and we identified
      factors associated with scores of >= A1 and >= F1. Our results clarified the
      timing and effectiveness of PLB. RESULTS: The incidences of scores of >= A1 and
      >= F1 were 24.7% and 24.7%, respectively, at two years after LT and 42.3% and
      34.5%, respectively, at five years. Independent risk factors in a multivariate
      analysis of a score of >= A1 at two years included >= 2 h of cold ischemic time,
      no acute cellular rejection and an alanine amino transaminase (ALT) level of >=
      20 IU/L (P = 0.028, P = 0.033 and P = 0.012, respectively); however, no risk
      factors were identified for a score of >= F1. Furthermore, no independent risk
      factors associated with scores of >= A1 and >= F1 at five years were identified
      using multivariate analysis. A ROC curve analysis of ALT at two years for a score
      of >= A1 demonstrated the recommended cutoff value for diagnosing >= A1 histology
      to be 20 IU/L. The incidence of scores of >= A2 or >= F2 at two years after LT
      was 3.4% (three cases), and all patients had an absolute score of >= A2. In
      contrast to that observed for PLBs at five years after LT, the incidence of
      scores of >= A2 or >= F2 was 20.0% (11 cases), and all patients had an absolute
      score of >= F2. In all cases, the dose of immunosuppressants was increased after
      the PLB, and all ten patients who underwent a follow-up liver biopsy improved to
      scores of <= A1 or F1. CONCLUSION: PLB at two years after LT is an unnecessary
      examination, because the serum ALT level reflects portal inflammation. In
      addition, immunosuppressive therapy should be modulated to maintain the ALT
      concentration at a level less than 20 IU/L. PLB at five years is an excellent
      examination for the detection of early reversible graft fibrosis because no serum
      markers reflect this finding.

PMID- 24914390
TI  - Novel method for extracting exosomes of hepatocellular carcinoma cells.
AB  - AIM: To develop a novel method for the rapid and efficient extraction of exosomes
      secreted by tumor cells. METHODS: Unlike the traditional extraction method, the
      supernatants of cell cultures were concentrated, and the exosomes were isolated
      promptly and effectively using a novel nanomaterial called ExoQuick. Coomassie
      brilliant blue staining was used for protein quantification, and the morphology
      of the exosomes extracted by both methods was visualized by transmission electron
      microscopy. Exosome marker proteins were detected by Western blot analysis. Two
      potential hepatoma-associated proteins, tissue transglutaminase 2 (TGM2) and
      annexin A2, were analyzed. RESULTS: The exosomes separated by the new extraction
      assay based on the nanomaterial were disc-shaped, intact vesicles with lipid
      bilayer membranes. They were approximately 30-100 nm in diameter, which is
      similar to the diameter of exosomes isolated by the traditional method. The
      protein concentration of exosomes extracted by the new method was approximately
      780 MUg/10(8) cells, and therefore, it was 19 times higher than that of exosomes
      extracted in the traditional manner. There were differences between the total
      proteins of Huh-7 cells and the exosomal proteins. Typical exosome proteins, such
      as the transmembrane protein CD63 and heat shock protein 70, were confirmed. Two
      potential hepatoma-associated proteins were also identified. TGM2 was first found
      to exist in the exosomes of human liver cancer cells, but annexin A2 was not
      secreted into exosomes. CONCLUSION: The new extraction method based on the
      nanomaterial is quick and efficient. The cancer-associated protein TGM2 can be
      secreted through an exosome-mediated non-classical secretion pathway, and it may
      be a valuable tumor marker.

PMID- 24914392
TI  - Toll-like receptor 4 polymorphisms to determine acute pancreatitis susceptibility
      and severity: a meta-analysis.
AB  - AIM: To investigate the correlation of toll-like receptor 4 (TLR4) gene Asp299Gly
      and Thr399Ile polymorphisms and acute pancreatitis (AP) risk and severity.
      METHODS: To get a more precise estimation of the relationship, a comprehensive
      search was performed to examine all the eligible studies of TLR4 Asp299Gly and
      Thr399Ile polymorphisms and AP risk. The odds ratios with 95% confidence
      intervals were used to assess the strength of the association. Publication bias
      was analyzed by Begg's funnel plots. RESULTS: In total, six studies with 1255
      cases and 998 controls were included in this meta-analysis. Totally, no
      significant associations were found between TLR4 Asp299Gly or Thr399Ile
      polymorphisms and AP risk using five models with high homogeneity (P > 0.05).
      Furthermore, stratification analysis by ethnicity or assay also found no
      significant association in these two polymorphisms (P > 0.05), and TLR4 Asp299Gly
      was not associated with AP severity (P > 0.05). In addition, no publication bias
      was found in these studies (P > 0.05). CONCLUSION: Our current meta-analysis
      suggests that TLR4 Asp299Gly and Thr399Ile polymorphisms may not be risk factors
      to AP susceptibility.

PMID- 24914391
TI  - Prognostic factors in patients with middle and distal bile duct cancers.
AB  - AIM: To identify the influence of the surgery type and prognostic factors in
      middle and distal bile duct cancers. METHODS: Between August 1990 and June 2011,
      data regarding the clinicopathological factors of 194 patients with surgical and
      pathological confirmation were collected. A total of 133 patients underwent
      resections (R0, R1, R2; n = 102, 24, 7), whereas 61 patients underwent
      nonresectional surgery. Either pancreaticoduodenectomy (PD) or bile duct
      resection (BDR) was selected according to the sites of tumors and co-morbidities
      of the patients after confirming resection margin by the frozen histology in all
      cases. Univariate and multivariate analyses of clinicopathologic factors were
      performed, utilizing the Kaplan-Meyer method and Cox hazard regression analysis.
      RESULTS: The overall 5-year survival rate for the 133 patients who underwent
      resection (R0, R1, and R2) was 41.2%, whereas no patients survived longer than 3
      years among the 61 patient who underwent nonresectional surgeries. The 5-year
      survival rate of the patients who underwent a PD (n = 90) was higher than the
      rate of those who underwent BDR (n = 43), although the difference was not
      statistically significant (46.6% vs 30.0% P = 0.105). However, PD had a higher
      rate of R0 resection than BDR (90.0% vs 48.8%, P < 0.0001). If R0 resection was
      achieved, PD and BDR showed similar survival rates (49.4% vs 46.5% P = 0.762).
      The 5-year survival rates of R0 and R1 resections were not significantly
      different (49.0% vs 21.0% P = 0.132), but R2 resections had lower survival (0%, P
      = 0.0001). Although positive lymph node, presence of perineural invasion,
      presence of lymphovascular invasion (LVI), 7th AJCC-UICC tumor node metastasis
      (TNM) stage, and involvement of resection margin were significant prognostic
      factors in univariate analysis, multivariate analysis identified only TNM stage
      and LVI as independent prognostic factors. CONCLUSION: PD had a greater
      likelihood of curative resection and R1 resection might have some positive
      impact. The TNM stage and LVI were independent prognostic factors.

PMID- 24914393
TI  - Rapid improvement in post-infectious gastroparesis symptoms with mirtazapine.
AB  - We report the case of a 34-year-old woman with severe post-infectious
      gastroparesis who was transferred from an outside medical facility for a second
      opinion regarding management. This patient had no prior history of
      gastrointestinal symptoms. However, in the aftermath of a viral illness, she
      developed two months of intractable nausea, vomiting, and oral intake intolerance
      that resulted in numerous hospitalizations for dehydration and electrolyte
      disturbances. A solid-phase gastric emptying scan had confirmed delayed emptying,
      confirming gastroparesis. Unfortunately, conventional pro-kinetic agents and
      numerous anti-emetic drugs provided little or no relief of the patient's
      symptoms. At our institution, the patient experienced a cessation of vomiting,
      reported a significant reduction in nausea, and tolerated oral intake shortly
      after taking mirtazapine. Based on mirtazapine's primary action as a serotonin (5
      HT) 1a receptor agonist, we infer that this receptor system mediated the clinical
      improvement through a combination of peripheral and central neural mechanisms.
      This report highlights the potential utility of 5-HT1a agonists in the management
      of nausea and vomiting. We conclude that mirtazapine may be effective in treating
      symptoms associated with non-diabetic gastroparesis that are refractory to
      conventional therapies. 

PMID- 24914394
TI  - Deep endometriosis with pericolic lymph node involvement: a case report and
      literature review.
AB  - Deep infiltrating endometriosis is an often-painful disorder affecting women
      during their reproductive years that usually involves the structures of the
      pelvis and frequently the gastrointestinal tract. We present the case of a 37
      year-old female patient with an endometrial growth on the sigmoid colon wall
      causing pain, diarrhea and the presence of blood in the feces. The histology of
      the removed specimen also revealed the involvement of the utero-vesical fold, the
      recto-vaginal septum and a pericolic lymph node, which are all quite uncommon
      findings. To identify the endometrial cells, we performed immunohistochemical
      staining for CD10 and the estrogen and progesterone receptors. 

PMID- 24914395
TI  - Ehealth monitoring in irritable bowel syndrome patients treated with low
      fermentable oligo-, di-, mono-saccharides and polyols diet.
AB  - In the present study we report on changes in irritable bowel syndrome-severity
      scoring system (IBS-SSS) and irritable bowel syndrome-quality of life (IBS-QoL)
      in 19 IBS patients, aged 18 to 74 years (F/M: 14/5), during 12 wk registering
      their symptoms on the web-application (www.ibs.constant-care.dk). During a
      control period of the first 6-wk patients were asked to register their IBS-SSS
      and IBS-QoL on the web-application weekly without receiving any intervention.
      Thereafter, low fermentable oligo-, di-, mono-saccharides and polyols (FODMAP)
      diet (LFD) was introduced for the next 6 wk while continuing the registration.
      Though a small sample size a significant improvement in disease activity (IBS
      SSS) was observed during both the control period, median: 278 (range: 122-377), P
      = 0.02, and subsequently during the LFD period, median: 151 (range: 29-334), P <
      0.01. The IBS-QoL solely changed significantly during the LFD period, median: 67
      (37-120), P < 0.01. The significant reduction in disease activity during the
      control period shows a positive effect of the web-application on IBS symptoms
      when presented as a "traffic light". However adding the diet reduced IBS-SSS to <
      150, inactive to mild symptoms. In the future results from larger scale trials
      are awaited. 

PMID- 24914396
TI  - Solitary schwannoma of the gallbladder: a case report and literature review.
AB  - Schwannomas occurring in the gallbladder are extremely rare. Preoperative
      diagnosis of gallbladder schwannomas appears to be very difficult because they
      are normally asymptomatic and are often found incidentally. Until now, only five
      cases have been reported in the literature. To our knowledge, the contrast
      enhanced ultrasound (CEUS) features of gallbladder schwannomas have not been
      reported before in other studies. We treated a 55-year-old male patient with
      gallbladder schwannoma in China. He had no symptoms, and the lesion was
      incidentally found by conventional ultrasound (US) when performing a health
      examination. The patient had normal liver function; moreover, serum
      carcinoembryonic antigen and alpha-fetoprotein were within the normal ranges. The
      lesion showed no blood flow signals on color Doppler US, and the wall beneath the
      lesion was intact on CEUS. The lesion was believed to be a benign entity; in
      addition, gallbladder adenomyomatosis was suspected. A laparoscopic
      cholecystectomy was performed to remove the mass. Pathological examination
      revealed that the tumor was mainly composed of spindle-shaped cells; neither
      atypical cells nor signs of malignancy were found. Immunohistochemical staining
      showed a strong positive S-100 protein reaction. Vimentin and CD56 staining were
      also positive, whereas CD34 and CD117 were negative. Finally, the lesion was
      diagnosed as schwannoma. Herein, we report the case; the associated literature is
      also reviewed. 

PMID- 24914397
TI  - Reversible posterior leukoencephalopathy syndrome induced by bevacizumab plus
      chemotherapy in colorectal cancer.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare brain
      capillary leak syndrome, characterized by clinical symptoms of headache, visual
      loss, seizures and altered mental functioning. This syndrome is usually
      reversible and is associated with hypertension, nephropathy, and use of
      immunosuppressive medication and cytotoxic agents. We describe two rare cases of
      RPLS occurring in colorectal cancer, both of which presented with coma, that we
      believe can be directly attributed to bevacizumab, a monoclonal antibody that
      inhibits the angiogenesis of tumours by specifically blocking vascular
      endothelial growth factor. We analysed the clinical features, risk factors and
      outcomes of RPLS in these two patients, and although no typical finding was
      identified on imaging examination, we found that inadequate blood pressure
      control was one of the risk factors leading to RPLS and that supportive treatment
      including intensive blood pressure control improved outcomes. Due to the
      increasing use of bevacizumab in colorectal cancer, clinicians should be aware of
      this potential complication. 

PMID- 24914398
TI  - Application of blunt dissection in ESD of a gastric submucosal tumor.
AB  - We performed endoscopic submucosal dissection of a gastric fundus tumor. It was
      difficult to strip the tumor completely due to space limitation, and we used
      blunt dissection to remove the tumor quickly and safely. Firstly, the basal area
      of the 2.5 cm submucosal tumor located in the gastric fundus was cut open, and
      the mucosa was dissected. The tumor was difficult to peel, therefore, a snare was
      used and the tumor was pulled and tightened slightly. Short electronic
      coagulation was used during the procedure. The tumor was then bluntly dissected.
      This method ensured rapid and complete removal of the tumor. 

PMID- 24914399
TI  - Nonlinear magneto-viscoelasticity of transversally isotropic magneto-active
      polymers.
AB  - Iron-filled magnetorheological polymers, when cured in the presence of a magnetic
      field, result in having a transversely isotropic structure with iron particles
      forming chains along the direction of applied magnetic induction. In this work,
      we model the magneto-viscoelastic deformation (and magnetization) process of such
      polymers. Components of the deformation gradient and the applied magnetic
      induction in the direction of anisotropy are considered to be additional
      arguments of the energy density function. The existence of internal damping
      mechanisms is considered by performing a multiplicative decomposition of the
      deformation gradient and an additive decomposition of the magnetic induction into
      equilibrium and non-equilibrium parts. Energy density functions and evolution
      laws of the internal variables are proposed that agree with the laws of
      thermodynamics. In the end, we present solutions of some standard deformation
      cases to illustrate the theory. In particular, it is shown that the orientation
      of resultant magnetic field and principal stress directions change with time
      owing to viscoelastic evolution.

PMID- 24914400
TI  - Pharmacokinetics of tramadol after subcutaneous administration in a critically
      ill population and in a healthy cohort.
AB  - BACKGROUND: Tramadol is an atypical centrally acting analgesic agent available as
      both oral and parenteral preparations. For patients who are unable to take
      tramadol orally, the subcutaneous route of administration offers an easy
      alternative to intravenous or intramuscular routes. This study aimed to
      characterise the absorption pharmacokinetics of a single subcutaneous dose of
      tramadol in severely ill patients and in healthy subjects. METHODS/DESIGN: Blood
      samples (5 ml) taken at intervals from 2 minutes to 24 hours after a subcutaneous
      dose of tramadol (50 mg) in 15 patients (13 male, two female) and eight healthy
      male subjects were assayed using high performance liquid chromatography.
      Pharmacokinetic parameters were derived using a non-compartmental approach.
      RESULTS: There were no statistically significant differences between the two
      groups in the following parameters (mean +/- SD): maximum venous concentration
      0.44 +/- 0.18 (patients) vs. 0.47 +/- 0.13 (healthy volunteers) mcg/ml (p =
      0.67); area under the plasma concentration-time curve 177 +/- 109 (patients) vs.
      175 +/- 75 (healthy volunteers) mcg/ml*min (p = 0.96); time to maximum venous
      concentration 23.3 +/- 2 (patients) vs. 20.6 +/- 18.8 (healthy volunteers)
      minutes (p = 0.73) and mean residence time 463 +/- 233 (patients) vs. 466 +/- 224
      (healthy volunteers) minutes (p = 0.97). CONCLUSIONS: The similar time to maximum
      venous concentration and mean residence time suggest similar absorption rates
      between the two groups. These results indicate that the same dosing regimens for
      subcutaneous tramadol administration may therefore be used in both healthy
      subjects and severely ill patients. TRIAL REGISTRATION: ACTRN12611001018909.

PMID- 24914402
TI  - Low-intensity and moderate exercise training improves autonomic nervous system
      activity imbalanced by postnatal early overfeeding in rats.
AB  - BACKGROUND: Postnatal early overfeeding and physical inactivity are serious risk
      factors for obesity. Physical activity enhances energy expenditure and consumes
      fat stocks, thereby decreasing body weight (bw). This study aimed to examine
      whether low-intensity and moderate exercise training in different post-weaning
      stages of life is capable of modulating the autonomic nervous system (ANS)
      activity and inhibiting perinatal overfeeding-induced obesity in rats. METHODS:
      The obesity-promoting regimen was begun two days after birth when the litter size
      was adjusted to 3 pups (small litter, SL) or to 9 pups (normal litter, NL). The
      rats were organized into exercised groups as follows: from weaning until 90-day
      old, from weaning until 50-day-old, or from 60- until 90-days-old. All
      experimental procedures were performed just one day after the exercise training
      protocol. RESULTS: The SL-no-exercised (SL-N-EXE) group exhibited excess weight
      and increased fat accumulation. We also observed fasting hyperglycemia and
      glucose intolerance in these rats. In addition, the SL-N-EXE group exhibited an
      increase in the vagus nerve firing rate, whereas the firing of the greater
      splanchnic nerve was not altered. Independent of the timing of exercise and the
      age of the rats, exercise training was able to significantly blocks obesity onset
      in the SL rats; even SL animals whose exercise training was stopped at the end of
      puberty, exhibited resistance to obesity progression. Fasting glycemia was
      maintained normal in all SL rats that underwent the exercise training,
      independent of the period. These results demonstrate that moderate exercise,
      regardless of the time of onset, is capable on improve the vagus nerves
      imbalanced tonus and blocks the onset of early overfeeding-induced obesity.
      CONCLUSIONS: Low-intensity and moderate exercise training can promote the
      maintenance of glucose homeostasis, reduces the large fat pad stores associated
      to improvement of the ANS activity in adult rats that were obesity-programmed by
      early overfeeding.

PMID- 24914401
TI  - The Alaris auditory evoked potential monitor as an indicator of seizure
      inducibility and duration during electroconvulsive therapy: an observational
      study.
AB  - BACKGROUND: Precise control of anesthetic depth during electroconvulsive therapy
      (ECT) is crucial because most intravenous anesthetics have anticonvulsant
      effects. In this study, we investigated the association between anesthetic depth
      measured by the Alaris auditory evoked potential index (AAI) and seizure
      inducibility and seizure duration during ECT. METHODS: Sixty-four ECTs were
      evaluated in 12 consecutive patients. General anesthesia was performed with a
      thiopental-based method. The relationship between the pre-ictal AAI, seizure
      activity and seizure duration was analyzed, and a possible threshold pre-ictal
      AAI to induce a seizure duration of at least 25 seconds was calculated. RESULTS:
      Forty-one of the 64 ECT stimuli successfully induced seizure activity that lasted
      longer than 25 seconds. Pre-ictal AAI was significantly correlated to seizure
      duration (r = 0.54, p < 0.001) and the threshold pre-ictal AAi value was
      calculated to be 26 (area under curve: 0.76, sensitivity: 70.3% and specificity:
      73.9%, p < 0.001). ECT with a pre-ictal AAI ? 26 had a higher incidence of
      successful seizure activity ( p < 0.001) and a longer seizure duration (55 +/- 35
      v.s. 21 +/- 27 seconds, p < 0.001). CONCLUSION: Maintenance of a pre-ictal AAI
      value ? 26 was associated with an increased incidence of successful seizure
      activities and a longer seizure duration. This is the first report to investigate
      Alaris AEP monitoring during ECT.

PMID- 24914403
TI  - Association between mental demands at work and cognitive functioning in the
      general population - results of the health study of the Leipzig research center
      for civilization diseases (LIFE).
AB  - BACKGROUND: The level of mental demands in the workplace is rising. The present
      study investigated whether and how mental demands at work are associated with
      cognitive functioning in the general population. METHODS: The analysis is based
      on data of the Health Study of the Leipzig Research Centre for Civilization
      Disease (LIFE). 2,725 participants aged 40-80 years underwent cognitive testing
      (Trail-Making Test, Verbal Fluency Test) and provided information on their
      occupational situation. Participants over the age of 65 years additionally
      completed the Mini-Mental State Examination. Mental demands at work were rated by
      a standardized classification system (O*NET). The association between mental
      demands and cognitive functioning was analyzed using Generalized Linear Modeling
      (GENLIN) adjusted for age, gender, self-regulation, working hour status,
      education, and health-related factors. RESULTS: Univariate as well as
      multivariate analyses demonstrated significant and highly consistent effects of
      higher mental demands on better performance in cognitive testing. The results
      also indicated that the effects are independent of education and intelligence.
      Moreover, analyses of retired individuals implied a significant association
      between high mental demands at work of the job they once held and a better
      cognitive functioning in old age. CONCLUSIONS: In sum, our findings suggest a
      significant association between high mental demands at work and better cognitive
      functioning. In this sense, higher levels of mental demands - as brought about by
      technological changes in the working environment - may also have beneficial
      effects for the society as they could increase cognitive capacity levels and
      might even delay cognitive decline in old age.

PMID- 24914404
TI  - Environmentally evaluated HPLC-ELSD method to monitor enzymatic synthesis of a
      non-ionic surfactant.
AB  - BACKGROUND: N-Lauroyl-N-methylglucamide is a biodegradable surfactant derived
      from renewable resources. In an earlier study, we presented an enzymatic solvent
      free method for synthesis of this compound. In the present report, the HPLC
      method developed to follow the reaction between lauric acid/methyl laurate and N
      methyl glucamine (MEG) and its environmental assessment are described. RESULTS:
      Use of ultraviolet (UV) absorption or refractive index (RI) detectors did not
      allow the detection of N-methyl glucamine (MEG). With Evaporative light
      scattering detector ELSD, it was possible to apply a gradient elution, and detect
      MEG with a limit of detection, LOD = 0.12 MUg. A good separation of the peaks:
      MEG, lauric acid, product (amide) and by-product (amide-ester) was achieved with
      the gradient program with a run time of 40 min. The setting of ELSD detector was
      optimized using methyl laurate as the analyte. LC-MS/MS was used to confirm the
      amide and amide-ester peaks. We evaluated the greenness of the developed method
      using the freely available software HPLC-Environmental Assessment Tool (HPLC-EAT)
      and the method got a scoring of 73 HPLC-EAT units, implying that the analytical
      procedure was more environmentally benign compared to some other methods reported
      in literature whose HPLC-EAT values scored up to 182. CONCLUSION: Use of ELSD
      detector allowed the detection and quantification of the substrates and the
      reaction products of enzymatic synthesis of the surfactant, N-lauroyl-N
      methylglucamide. The developed HPLC method has acceptable environmental profile
      based on HPLC-EAT evaluation.

PMID- 24914405
TI  - Catatonic features in adolescents with schizophrenia with and without a comorbid
      pervasive developmental disorder.
AB  - BACKGROUND: Catatonia has been associated with both schizophrenia and pervasive
      developmental disorders. The aim of this study was to evaluate catatonic features
      among adolescents suffering from schizophrenia. Further, we compared these
      features between adolescents with a comorbid pervasive developmental disorder and
      those without one. Finally, we wanted to compare the profile of catatonia-like
      features of our schizophrenia patients to that described earlier among persons
      with autism spectrum disorders. METHODS: The study comprised a consecutive sample
      of 18 adolescents with schizophrenia (mean age 15.6 years, SD 1.4) and their
      families. Diagnosis of schizophrenia was assessed with the Schedule for Affective
      Disorders and Schizophrenia for School-Aged Children - Present and Life-Time (K
      SADS-PL) for the DSM-IV. The Diagnostic Interview for Social and Communication
      Disorders version 11 was used to assess catatonic features. RESULTS: All
      adolescents with schizophrenia had showed some lifetime catatonic features.
      Approximately 78% of them had already expressed these features before the age of
      10. The number of catatonic features before the age of 10 was significantly
      higher among the adolescents with a comorbid pervasive developmental disorder
      compared to those without one. The numbers of catatonic features after the age of
      10 did not significantly differ between the two groups. Over three-quarters of
      schizophrenia patients shared four lifetime catatonic features: "lacks facial
      expression", "odd intonation", "poor eye contact" and "lack of cooperation".
      CONCLUSIONS: Adolescent schizophrenia patients with a comorbid pervasive
      developmental disorder show many catatonic features in childhood whereas those
      without one seem to develop these features first in adolescence. Catatonic
      features exhibited by adolescents with schizophrenia resemble those described
      among persons with pervasive developmental disorders without schizophrenia.

PMID- 24914407
TI  - Plasma concentrations of D-dimer and outcome of in vitro fertilization.
AB  - BACKGROUND: The activation of blood coagulation could contribute to the failure
      of in-vitro fertilization (IVF) techniques. The aim of this study was to assess
      the predictive value of D-dimer levels for pregnancy outcome in women undergoing
      IVF. FINDINGS: A prospective study was performed in 105 women undergoing IVF. D
      dimer was measured before and one week after the administration of recombinant
      human chorionic gonadotropin (r-hCG). The primary outcome of the study was
      clinical pregnancy. The mean age was 36 years (range 26 to 43 years). The main
      indications for IVF were infertility due to a tubaric (n = 21, 20%) or male
      factor (n = 37, 35%) and idiopathic infertility (n = 30, 29%) which altogether
      accounted for 84% of the total. Clinical pregnancy was achieved by 40/105 (38%)
      women of whom 32 (80%) delivered a live child. On the day of r-hCG
      administration, D-dimer concentrations were significantly higher in patients not
      achieving a clinical pregnancy (141 ng/dL vs. 115 ng/dL, p = 0.035) which
      remained statistically significant after correction for age and indications for
      IVF in multivariable analysis (p = 0.032). One week after r-hCG, the levels of D
      dimer were significantly increased both in women with and without a clinical
      pregnancy with no differences between the groups (748 ng/dL vs. 767 ng/dL, p =
      0.88). CONCLUSIONS: D-dimer concentrations seem to predict a higher risk of
      pregnancy failure in women undergoing IVF. If confirmed in future prospective
      studies, D-dimer could help identifying a group of patients who could benefit
      from prophylaxis to increase the pregnancy success rate.

PMID- 24914406
TI  - Abnormalities in spontaneous abortions detected by G-banding and chromosomal
      microarray analysis (CMA) at a national reference laboratory.
AB  - BACKGROUND: Cytogenetic evaluation of products of conception (POC) for
      chromosomal abnormalities is central to determining the cause of pregnancy loss.
      We compared the test success rates in various specimen types and the frequencies
      of chromosomal abnormalities detected by G-banding analysis with those found by
      Oligo-SNP chromosomal microarray analysis (CMA). We evaluated the benefit of CMA
      testing in cases of failed culture growth. METHODS: Conventional cytogenetic
      results of 5457 consecutive POC specimens were reviewed and categorized as
      placental villi, fetal parts, and unspecified POC tissue. The CMA was performed
      on 268 cases. Of those, 32 cases had concurrent G-banding results. The remaining
      236 cases included 107 cases with culture failure and 129 cases evaluated by CMA
      alone. RESULTS: The overall POC culture success rate was 75%, with the lowest for
      fetal parts (37.4%) and the highest for placental villi (81%). The abnormality
      rate was 58% for placental villi, but only 25% for fetal parts. Of the
      abnormalities detected, the most common were aneuploidies, including trisomy 16,
      triploidy, monosomy X, trisomy 22, trisomy 21 and trisomy 15, while the least
      encountered aneuploidies were trisomy 1, trisomy 19 and monosomies (except
      monosomy 21). Overall, POC specimens studied by CMA were successful in 89.6% of
      cases and yielded a 44.6% abnormality rate. CONCLUSIONS: Placental villi yielded
      higher rates of culture success and a higher percentage of abnormal karyotypes
      than did other specimen types. The Oligo-SNP CMA method has demonstrated a viable
      alternative to the G-banding method in view of its advantages in detection of
      submicroscopic genomic aberrations, shorter turnaround time due to elimination of
      time required for culture and a higher test success rate.

PMID- 24914409
TI  - The shaping of pharmaceutical governance: the Israeli case.
AB  - This article focuses on governance of the pharmaceutical sector in Israel. It
      traces the relationships between the state, industry, and sick funds from before
      the establishment of National Health Insurance (NHI) in 1995 to the beginning of
      this decade, in particular as they have grappled with the challenge of making
      national formulary decisions in a rational manner. Subsequent to the introduction
      of NHI there have been shifts in the modes and mix of governance. This research
      shows empirically that a relatively complex mix of hierarchical and network modes
      of governance can be successfully established over an extended period of time
      when flexibility is maintained through the implementation process. The system for
      defining and updating a standard basket of health services has coped well with
      the challenge of managing a range of difficult and potentially volatile
      stakeholder relationships in the pharmaceutical sector and of distancing
      ministers from controversies of funding and listing decisions. Government has
      succeeded in containing drug costs whilst still maintaining a basket of
      reimbursable drugs that, from an international perspective, is comprehensive and
      technologically advanced. On the other hand, network arrangements appear to have
      delayed the introduction of suitable accountability relationships and hindered
      their development. The state has traditionally played an intermediary role
      between unavoidable corporate interests of industry and sick funds, with little
      transparency and to the detriment of more pluralistic access to decision making.
      Governance arrangements in Israel appear to limit the potential and incentive of
      the state and the sick funds to realize their potential countervailing powers in
      subsidy and pricing decisions. 

PMID- 24914408
TI  - Development of CBAP-BPyne, a probe for gamma-secretase and presenilinase.
AB  - gamma-Secretase undergoes endoproteolysis of its catalytic subunit, presenilin
      (PS), to form PS N-terminal and C-terminal fragments (PS1-NTF/CTF), which
      generate the active site. PS endoproteolysis, catalyzed by presenilinase (PSase),
      remains poorly understood and requires novel chemical approaches for its
      mechanistic study. CBAP is a dual inhibitor that suppresses both gamma-secretase
      and PSase activities. To probe gamma-secretase and PSase activity in cells, we
      have synthesized the clickable photoaffinity probe CBAP-BPyne. We found that CBAP
      BPyne specifically labels PS1-NTF and signal peptide peptidase (SPP). CBAP-BPyne
      is a valuable tool to directly study the mechanism of endoproteolysis.

PMID- 24914410
TI  - Sunitinib significantly suppresses the proliferation, migration, apoptosis
      resistance, tumor angiogenesis and growth of triple-negative breast cancers but
      increases breast cancer stem cells.
AB  - The majority of triple-negative breast cancers (TNBCs) are basal-like breast
      cancers. However there is no reported study on anti-tumor effects of sunitinib in
      xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB
      231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS.
      Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA
      (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for
      measuring proliferation (3H-thymidine incorporation), migration (BD Invasion
      Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of
      sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB
      468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary
      gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100
      mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor
      angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem
      cells (CSCs) isolated from the tumors were determined by flow cytometry analysis
      using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly
      expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib
      significantly inhibited the proliferation, invasion, and apoptosis resistance in
      cultured basal like breast cancer cells. Sunitinib significantly increased the
      expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The
      xenograft models showed that oral sunitinib significantly reduced the tumor
      volume of TNBCs in association with the inhibition of tumor angiogeneisis, but
      increased breast CSCs. These findings support the hypothesis that the possibility
      should be considered of sunitinib increasing breast CSCs though it inhibits TNBC
      tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch
      expression and hypoxia may increase breast cancer stem cells. This work provides
      the groundwork for an innovative therapeutic strategy in TNBC therapy by using
      sunitinib plus gamma-secretase inhibitor to simultaneously target angiogenesis
      and CSC. 

PMID- 24914412
TI  - A novel compression garment with adhesive silicone stripes improves repeated
      sprint performance - a multi-experimental approach on the underlying mechanisms.
AB  - BACKGROUND: Repeated sprint performance is determined by explosive production of
      power, as well as rapid recovery between successive sprints, and there is
      evidence that compression garments and sports taping can improve both of these
      factors. METHODS: In each of two sub-studies, female athletes performed two sets
      of 30 30-m sprints (one sprint per minute), one set wearing compression garment
      with adhesive silicone stripes (CGSS) intended to mimic taping and the other with
      normal clothing, in randomized order. Sub-study 1 (n = 12) focused on cardio
      respiratory, metabolic, hemodynamic and perceptual responses, while neuronal and
      biomechanical parameters were examined in sub-study 2 (n = 12). RESULTS: In both
      sub-studies the CGSS improved repeated sprint performance during the final 10
      sprints (best P < 0.01, d = 0.61). None of the cardio-respiratory or metabolic
      variables monitored were altered by wearing this garment (best P = 0.06, d =
      0.71). Also during the final 10 sprints, rating of perceived exertion by the
      upper leg muscles was reduced (P = 0.01, d = 1.1), step length increased (P =
      0.01, d = 0.91) and activation of the m. rectus femoris elevated (P = 0.01, d =
      1.24), while the hip flexion angle was lowered throughout the protocol (best P <
      0.01, d = 2.28) and step frequency (best P = 0.34, d = 0.2) remained unaltered.
      CONCLUSION: Although the physiological parameters monitored were unchanged, the
      CGSS appears to improve performance during 30 30-m repeated sprints by reducing
      perceived exertion and altering running technique.

PMID- 24914411
TI  - Changing the course of comorbid eating disorders and depression: what is the role
      of public health interventions in targeting shared risk factors?
AB  - Public health has a productive history of improving global health due to its
      focus on reaching large populations using effective and scalable interventions.
      Yet, the marriage between evidence-based science and the implementation of
      community/public health interventions within mental illness remains
      underdeveloped. Research suggests that major depression is the most commonly
      cited comorbidity for eating disorders (EDs). Thus, identification of public
      health strategies that jointly impact depression and EDs, including shared risk
      factors, has the potential to significantly impact mental health suffering. The
      primary aim of this paper is to examine and discuss such public health approaches
      as well as explore cues taken from public health efforts to inform future
      directions in research and clinical practice. As a comprehensive review of all
      public health initiatives that address EDs and depression is beyond the scope of
      this paper, this paper reviews a series of programs/approaches that either are of
      large scale and/or have received empirical support. In particular, public health
      related interventions that aim to reduce variable risk factors associated with
      EDs and depression, as well as interventions that aim to reduce continuous
      measures of ED and depression symptoms are reviewed. To date, despite significant
      progress in modifying risk factors for EDs and depression, the field still lacks
      a public health study that has been appropriately designed and/or adequately
      powered to assess true ED/depression prevention effects. Further, although
      several programs show promise, many widely disseminated approaches lack empirical
      support, raising concerns about the potential for waste of limited resources. In
      summary, although the combination of prevention and public health based
      approaches appear to have merit when trying to move the needle on risk factors
      and symptoms associated with EDs and/or depression, further research is needed to
      investigate the reach and effectiveness of large scale dissemination efforts of
      such endeavors. 

PMID- 24914413
TI  - A case of complicated silicosis with a complex clinical course in a glass
      manufacturing worker.
AB  - We reported a case of complicated silicosis that occurred in a glass
      manufacturing plant worker who had presumably been exposed to low-concentration
      free silica for almost 20 years. To the best of our knowledge this report is the
      first in the Republic of Korea. The physician's first impression was cancer since
      the enlargement of neck and supraclavicuar lymph nodes had clearly progressed and
      metastasis was suspected in ultrasonography. However, it turned out to be
      reactive hyperplasia and anthracosis. Although lung cancer was suspected and
      tests were performed in 2 hospitals due to repetitive cough and dyspnea, along
      with weight loss of approximately 10% over the course of 7 months, the patient
      was eventually diagnosed with complicated silicosis and pneumothorax occurred
      after 1 year. Herein, we report this case with a literature review. 

PMID- 24914415
TI  - Evaluation of liver fibrosis with T1rho MR imaging.

PMID- 24914416
TI  - Lessons learned from imaging mouse ovarian tumors: the route of probe injection
      makes a difference.
AB  - Patients with ovarian cancer often develop small metastatic lesions in their
      peritoneal cavities. Fluorescent-imaging probes that can highlight these small
      lesions have significant value for guiding procedures and treatment decisions. In
      this animal study, we demonstrated that intraperitoneal (IP) delivery of a
      protease-sensitive fluorescent probe resulted in the labeling of all tumors
      regardless of their sizes with low background signals in organs. Conversely,
      intravenous (IV) injections of the probe resulted in high signals in most organs
      and large tumors (>5 mm) but not in any of the small lesions (<2 mm). 

PMID- 24914414
TI  - "Killing Two Birds with One Stone": Alcohol Use Reduction Interventions with
      Potential Efficacy in Enhancing Self-Control.
AB  - We review interventions with empirical support for reducing alcohol use and
      enhancing self-control. While any intervention that decreases drinking could
      improve self-control, we focus here on interventions with evidence of direct
      benefit for both indications. Although no intervention yet shows strong evidence
      for dual efficacy, multiple interventions have strong evidence for one indication
      and solid or suggestive evidence for the other. Among pharmacotherapies, opioid
      antagonists currently have the best evidence for reducing alcohol use and
      enhancing self-control. Nicotinic partial agonist varenicline also appears to be
      efficacious for alcohol use and self-control. Many psychosocial and behavioral
      interventions (e.g., cognitive behavioral therapy, contingency management,
      mindfulness training) may have efficacy for both indications based on purported
      mechanisms of action and empirical evidence. Cognitive bias modification and
      neurophysiological interventions have promise for alcohol use and self-control as
      well and warrant further research. We offer several other suggestions for future
      research directions.

PMID- 24914417
TI  - Metal artifacts from titanium and steel screws in CT, 1.5T and 3T MR images of
      the tibial Pilon: a quantitative assessment in 3D.
AB  - Radiographs are commonly used to assess articular reduction of the distal tibia
      (pilon) fractures postoperatively, but may reveal malreductions inaccurately.
      While magnetic resonance imaging (MRI) and computed tomography (CT) are potential
      three-dimensional (3D) alternatives they generate metal-related artifacts. This
      study aims to quantify the artifact size from orthopaedic screws using CT, 1.5T
      and 3T MRI data. Three screws were inserted into one intact human cadaver ankle
      specimen proximal to and along the distal articular surface, then CT, 1.5T and 3T
      MRI scanned. Four types of screws were investigated: titanium alloy (TA),
      stainless steel (SS) (O =3.5 mm), cannulated TA (CTA) and cannulated SS (CSS) (O
      =4.0 mm, O empty core =2.6 mm). 3D artifact models were reconstructed using
      adaptive thresholding. The artifact size was measured by calculating the
      perpendicular distance from the central screw axis to the boundary of the
      artifact in four anatomical directions with respect to the distal tibia. The
      artifact sizes (in the order of TA, SS, CTA and CSS) from CT were 2.0, 2.6, 1.6
      and 2.0 mm; from 1.5T MRI they were 3.7, 10.9, 2.9, and 9 mm; and 3T MRI they
      were 4.4, 15.3, 3.8, and 11.6 mm respectively. Therefore, CT can be used as long
      as the screws are at a safe distance of about 2 mm from the articular surface.
      MRI can be used if the screws are at least 3 mm away from the articular surface
      except for SS and CSS. Artifacts from steel screws were too large thus obstructed
      the pilon from being visualised in MRI. Significant differences (P<0.05) were
      found in the size of artifacts between all imaging modalities, screw types and
      material types, except 1.5T versus 3T MRI for the SS screws (P=0.063). CTA screws
      near the joint surface can improve postoperative assessment in CT and MRI. MRI
      presents a favourable non-ionising alternative when using titanium hardware.
      Since these factors may influence the quality of postoperative assessment,
      potential improvements in operative techniques should be considered. 

PMID- 24914418
TI  - Chemical shift imaging: preliminary experience as an alternative sequence for
      defining the extent of a bone tumor.
AB  - OBJECTIVE: To investigate chemical shift imaging (CSI) with in-phase and opposed
      phase (OP) gradient-echo sequences as an alternative sequence to spin-echo T1
      imaging for defining intra-medullary skeletal tumor extent. METHODS AND
      MATERIALS: This retrospective HIPAA-compliant study was approved by our
      institutional institutional review board (IRB). Twenty-three subjects with
      histologically-proven tumors (17 appendicular, 6 axial) underwent magnetic
      resonance imaging (MRI) with T1-weighted spin echo (T1SE), fluid-sensitive, CSI,
      and contrast-enhanced T1 sequences. One observer recorded intra-medullary tumor
      extent (millimeters), with 153 total measurements on each sequence. Red marrow
      grade [0 (none), 1 (<50%), 2 (50-75%) and 3 (>75%)] in each bone was recorded.
      Tumor extent on different sequences was compared (Student's t-test); the impact
      of red marrow grade on measurements was assessed (Spearman's correlation
      coefficient). RESULTS: There was good agreement between measurements of tumor
      extent on T1SE and CSI sequences in all cases (T1SE-CSI measurement difference
      range 0-13.2 mm, P>0.05). Measurements from other sequences were significantly
      different from those of T1SE (P<0.05). As red marrow grade in the bone increased,
      a significant increase in measurement difference obtained on T1SE and CSI
      sequences was observed (P<0.001). CONCLUSIONS: CSI is a potential alternative
      technique to T1SE imaging for defining the intra-medullary extent of a bone
      tumor, possibly especially useful in regions with abundant red marrow. ADVANCE IN
      KNOWLEDGE: CSI could be an alternative technique to T1SE imaging for defining the
      intra-medullary extent of bone tumor by abundant red marrow in the surrounding
      bone.

PMID- 24914419
TI  - Diagnostic accuracy of MR imaging to identify and characterize focal liver
      lesions: comparison between gadolinium and superparamagnetic iron oxide contrast
      media.
AB  - To compare the diagnostic value of gadolinium (Gd) and ultrasmall
      superparamagnetic iron oxide (SPIO) contrast media for characterization of focal
      liver lesions (FLL), we retrospectively evaluated the results of magnetic
      resonance (MR) imaging in 68 patients (40 M, 28 F, age from 22 to 81 yrs) of
      which 36 with diagnosis of colo-rectal cancer, 26 with hepatic cirrhosis and 6
      with incidental imaging detection of FLL. MR (Gyroscan Intera 1.5 T, Philips
      Medical Systems) study was performed using T1 and T2 fast-field-echo (FFE) and T2
      turbo-spin-echo (TSE) sequences in axial and coronal views. Dynamic multi-phases
      gadolinium Gd-enhanced T1-FFE-Bh images were obtained in arterial, portal and
      equilibrium phases, followed by SPIO-enhanced T2-FFE scans. A qualitative
      analysis of pre- and post-contrast MR images to classify FLL as benign or
      malignant was performed using a 3-point scoring system: 0= benign; 1= suspicious
      for malignancy; 2= malignant. A total of 118 lesions were evaluated. In
      particular, histology (n=18), cytology (n=14) or clinical-imaging follow-up data
      (n=86) demonstrated 4 adenomas, 29 cysts, 3 focal steatosis, 25 hemangiomas, 1
      focal vascular abnormality, 5 fibrotic lesions as well as 13 regenerative
      nodules, 6 dysplastic, 14 hepatocellular carcinomas (HCC), 17 metastasis and 1
      cholangiocarcinoma. For MR imaging, diagnostic accuracy, sensitivity,
      specificity, positive (PPV) and negative (NPV) predictive values of Gd vs. SPIO
      images were respectively 83% vs. 92%, 79% vs. 74%, 85% vs. 99% (P=0.002), 68% vs.
      96% (P=0.005) and 91% vs. 90%, respectively. The results suggest that SPIO-MR
      provides a diagnostic incremental value, as specificity and PPV, particularly to
      characterize FLL compared to Gd-MR; thus, we strongly recommend the use of SPIO
      when liver lesion characterization is requested and Gd images are uncertain. 

PMID- 24914420
TI  - A modified technique for real time ultrasound guided pediatric percutaneous renal
      biopsy: the angled tangential approach.
AB  - AIM: Pediatric renal biopsy may result in serious hemorrhagic complications,
      requiring additional diagnostic procedures, blood transfusion, vascular
      interventions, and prolongation of hospitalization. The aim of the present study
      was to propose the angled tangential approach technique for real-time ultrasound
      guided pediatric percutaneous renal biopsy. METHODS: A retrospective analysis of
      166 percutaneous biopsies from June 2004 to May 2009 was performed. Patients'
      medical records, pathology results, and complications were reviewed. RESULTS: No
      major complications were seen in the study group. The most frequently occurring
      minor complication was macroscopic hematuria, which occurred at the rate of 9.6%.
      Hematoma was detected in three cases and regressed spontaneously in all cases.
      CONCLUSIONS: The angled tangential approach is a safe technique and an
      alternative option in pediatric percutaneous renal biopsies.

PMID- 24914423
TI  - A large asymptomatic foreign body in larynx and trachea.
AB  - A 41-year-old asymptomatic man was referred to emergency department complaining
      of severe dyspnea. He had a history of psychosis and had been taking Biperiden
      and Lithium carbonate since 17 years ago. Imaging studies showed multiple foreign
      bodies in the trachea, which were extracted. 

PMID- 24914422
TI  - Imaging features on sonography and MRI in a case of lipofibromatous hamartoma of
      the median nerve.
AB  - Lipofibromatous hamartomas are rare benign tumours of Peripheral nerves. Median
      nerve is most common affected nerve involved in about 80 percent of the cases.
      Approximately 92 cases have been reported so far. We present a case of
      lipofibromatous hamartoma of median nerve diagnosed on sonography and magnetic
      resonance imaging (MRI). These rare lesions are an important entity to be known
      to radiologists because their imaging features are quite pathognomonic and allow
      for confident diagnosis negating the need for biopsy. 

PMID- 24914421
TI  - Positron emission tomography/computerized tomography in lung cancer.
AB  - Positron emission tomography (PET) using 2-(18F)-flouro-2-deoxy-D-glucose (FDG)
      has emerged as a useful tool in the clinical work-up of lung cancer. This review
      article provides an overview of applications of PET in diagnosis, staging,
      treatment response evaluation, radiotherapy planning, recurrence assessment and
      prognostication of lung cancer. 

PMID- 24914424
TI  - Spontaneous asymptomatic gallbladder perforation.
AB  - Gallstone disease is common. However, a proportion of patients are asymptomatic
      and remain undiagnosed until the occurrence of complications. Common
      complications include acute cholecystitis, biliary obstruction, acute
      pancreatitis and cholangitis. Severe complications include gallbladder
      perforation, Mirizzi syndrome and fistula formation are usually associated with
      significant morbidity and mortality. We report a case of asymptomatic spotaneous
      gallbladder perforation due to acute cholecystitis. 

PMID- 24914425
TI  - Short-term effect of mechanical plaque control on salivary mutans streptococci in
      preschool children.
AB  - PURPOSE: To determine the effect of mechanical tooth cleaning by toothbrush and
      dental floss on mutans streptococci in the saliva of preschool children.
      MATERIALS AND METHODS: This blinded, randomised controlled clinical trial
      included 54 3-year-old preschool children with detectable mutans streptococci in
      saliva. The children were randomly divided into a test and a control group.
      Dental college students cleaned the teeth of test group participants with
      toothbrush and dental floss under the indication of a plaque disclosing agent
      once a day. The control group received no intervention. Dentocult SM Strip mutans
      (D-SM) strips were used to test the mutans streptococci in saliva. RESULTS: The D
      SM test scores declined from 1.82 to 0.95 for the test group after the teeth were
      cleaned 10 times (P < 0.001) and the scores increased to 1.62 after tooth
      cleaning ceased for 2 weeks (P > 0.05 compared with baseline). The D-SM level of
      the control group did not change significantly. CONCLUSION: Meticulous and
      continuous plaque control with toothbrush and dental floss can decrease the
      mutans streptococci level in preschool children. However, the effect ceased as
      the intervention ceased.

PMID- 24914426
TI  - Antibacterial effects of fluoride varnish compared with chlorhexidine plus
      fluoride in disabled children.
AB  - PURPOSE: To evaluate the effects of fluoride varnish vs a combination of
      chlorhexidine-thymol varnish plus a gel containing chlorhexidine and fluoride on
      oral hygiene and caries prevention in disabled children. MATERIALS AND METHODS:
      Ninety patients aged 3-17 years who were treated under general anaesthesia were
      randomly assigned into three groups as follows: group 1: Fluor Protector (0.1%
      fluoride varnish); group 2: Cervitec Plus (1% chlorhexidine- 1% thymol varnish) +
      Cervitec Gel (0.2% chlorhexidine-0.2% sodium fluoride); group 3: control
      (toothbrushing only). Mutans streptococci (MS) and lactobacilli (LB) levels,
      visible plaque index (VPI) and gingival bleeding index (GBI) were evaluated at
      four stages: T0, before general anaesthesia; T1, one month after treatment; T2,
      six months after treatment; T3, twelve months after treatment. The data were
      evaluated using Kruskal-Wallis and Mann-Whitney U-tests (P < 0.05). RESULTS:
      Groups 1 and 2 showed significantly lower scores than group 3 for all parameters
      at T1 and T2. No statistically significant difference was detected among any of
      the the groups at T3 (P > 0.05). CONCLUSION: The use of materials that include
      both fluoride and chlorhexidine as routine treatment of children with disability
      may increase the success of restorations by improving oral hygiene, reduce the
      need for future restorative treatments and thus the need for general anaesthesia.

PMID- 24914427
TI  - Impact of empowerment on toothbrushing and diabetes management.
AB  - PURPOSE: To assess the impact of empowerment (health coaching, HC) on
      toothbrushing self-efficacy (TBSE) and toothbrushing frequency (TB) and their
      effects on diabetes management (HbA1c, physical activity) and quality of life in
      comparison to health education (HE) among patients with diabetes type 2 (DM2).
      MATERIALS AND METHODS: The data (HbA1c [glycated haemoglobin], TB, physical
      activity, TBSE, quality of life) were collected at baseline and at post
      intervention at outpatient clinics of two hospitals in Istanbul, Turkey.
      Participants were allocated randomly to HC (n = 77) and HE (n = 109) groups.
      RESULTS: At baseline, there were no statistical differences between HC and HE
      groups in terms of all measures (P > 0.05). At post-intervention, there was
      improvement in oral health- and diabetes-related variables in the HC group,
      whereas only TBSE and TB slightly improved in the HE group (P < 0.05). At post
      intervention among patients brushing their teeth at least once a day, HC group
      patients were more likely to be physically active and to have high self-efficacy
      than those in HE group (P < 0.01). TBSE was correlated with favourable HbA1c
      levels (< 6.5%) in the HC group and quality of life (P < 0.05) in both groups.
      CONCLUSION: The findings show that HC-based empowerment towards improving self
      efficacy is more effective at improving toothbrushing behaviour than is HE and
      that interaction contributes significantly to diabetes management in terms of
      reduced HbA1c, increased physical activity and quality of life. TBSE can be a
      practical starting point for empowerment and toothbrushing can be used as an
      effective and practical behaviour to observe personal success in diabetes
      management.

PMID- 24914428
TI  - Occlusal splints and quality of life - does the patient-provider relationship
      matter?
AB  - PURPOSE: Occlusal splints are often prescribed when treating patients with
      bruxism. The objectives were to determine (a) whether using occlusal splints
      improves patients' oral health-related quality of life (ohrqol) and (b) whether
      the quality of the patient-provider relationship affects these patients' splint
      related responses and their ohrqol. MATERIALS AND METHODS: Survey data were
      collected from 233 patients who had received bite splints during the 5 years
      prior to data collection. RESULTS: The data showed that 5% of these patients had
      never used their splint, 20% had used it in the past, and 75% still used it at
      the time of data collection. Patients using the splint agreed more strongly that
      their current oral health status had improved, had more positive splint-related
      responses and more positive pain-related ohrqol scores than patients who were no
      longer using the splint. The more patients agreed that they were satisfied with
      their provider, the more positively they evaluated their bite splints and the
      more positive was their ohrqol. CONCLUSIONS: Bite splint users have more positive
      splint-related responses and a better pain-related ohrqol than patients who
      received a bite splint but do not use it any longer. The quality of the patient
      provider relationship plays an important role in the patients' splint-related
      responses as well as in the degree to which patients' ohrqol improves.

PMID- 24914429
TI  - Dental hygienists working in schools - a two-year oral health intervention
      programme in swedish secondary schools.
AB  - PURPOSE: To investigate the possibility of influencing adolescents' caries
      incidence, knowledge and attitudes to oral health and tobacco through a school
      based oral health intervention programme. MATERIALS AND METHODS: Four schools in
      a county in Sweden were randomised to one intervention and one control group. At
      the intervention schools, two dental hygienists worked 4 h every week for two
      years. Health education and preventive measures, such as fluoride varnish
      treatments every 6 months, were performed. The control group had no intervention.
      The study included a total of 534 participants aged 12-16 years. Outcome
      variables of the study were 1) caries incidence assessed on bite-wing radiographs
      and 2) knowledge and attitudes measured through questionnaires. RESULTS: The
      intervention programme impacted on the incidence of enamel caries, while no
      effect on dentin caries could be seen. Data from the questionnaires showed that
      the adolescents considered their teeth as important. Adolescents in the
      intervention group had better knowledge about oral health and oral hygiene
      compared to the control group after the two years, but no impact on attitudes
      toward tobacco could be seen. A majority of the adolescents were positive to the
      education about oral health and tobacco and they believed that the dental
      hygienists would help them improve their oral health. CONCLUSIONS: Although the
      effects of the intervention as regards to caries incidence, knowledge and
      attitudes were limited, the presence of dental hygienists in school was
      appreciated by the adolescents and seemed to increase their interest in their
      oral health.

PMID- 24914430
TI  - Antibiotic prophylaxis of infective endocarditis in dentistry: clinical approach
      and controversies.
AB  - PURPOSE: Infective endocarditis (IE) in high-risk patients is a potentially
      severe complication which justifies the administration of antibiotics before
      invasive dental treatment. This literature review presents the current guidelines
      for antibiotic prophylaxis and discusses the controversial aspects related to the
      antibiotic administration for prevention of IE. RESULTS: According to the
      guidelines of the American Heart Association, individuals who are at risk to
      develop IE following an invasive dental procedure still benefit from antibiotic
      prophylaxis. In contrast, the guidelines of the National Institute for Health and
      Clinical Excellence in England and Wales have recommended that prophylactic
      antibiotic treatment should no longer be performed in any at-risk patient.
      Bacteraemia following daily routines such as eating and toothbrushing may be a
      greater risk factor for the development of IE than the transient bacteraemia that
      follows an invasive dental procedure. However, a single administration of a
      penicillin derivate 30 to 60 minutes pre-operatively still represents the main
      prophylactic strategy to prevent bacteraemia. CONCLUSIONS: Presently, there is
      not enough evidence that supports and defines the administration of antibiotics
      to prevent IE. The authors suggest performing a risk-benefit evaluation in light
      of the available guidelines before a decision is made about administration.

PMID- 24914431
TI  - Hepatitis C virus and dental health workers: an update.
AB  - Hepatitis C virus (HCV) infection is a worldwide health problem, affecting over
      130 million individuals. The virus is transmitted parenterally, making health
      care professionals a risk group for infection. For this reason it is important
      that dental health-care workers recognise the symptoms of the infection, which
      can be present in the oral cavities of hepatitis C-infected individuals.
      Moreover, dental health-care workers should know how to manage hepatitis C
      infected individuals during dental treatment and the measures to prevent
      nosocomial spread of HCV. Thus, the purpose of this study was to perform a review
      of HCV epidemiology, natural history, transmission, diagnosis, treatment and
      prevention focusing on oral manifestations in and dental management strategies
      for HCV-infected individuals. 

PMID- 24914432
TI  - Relationship between mandibular incisor irregularity and type of occlusion in
      ankyloglossia.
AB  - PURPOSE: To investigate the relationship between the lingual frenulum length with
      mandibular incisor irregularity and type of occlusion in children with
      ankyloglossia. MATERIALS AND METHODS: Eighty children aged between 7 and 12 years
      with ankyloglossia enrolled in the study. The patients were classified according
      to Kotlow's classification. Mandibular incisor crowding was measured and the
      molar relationship was determined. The data were analysed statistically using
      Fisher's exact test, X2 and Pearson's correlation. RESULTS: Of the 80 patients,
      45 (56.3%) had mild, 23 (28.8%) had moderate and 12 (15%) had severe
      ankyloglossia. Fifty-nine (73.8%) of the patients had mild irregularity, 18
      (22.5%) had moderate and 3 (3.8%) had severe irregularity. In 56 (70%) of the
      patients, Class I occlusion was observed, 17 (21.3%) had Class II and 7 (8.8%)
      had Class III occlusion. No significant differences were found between types of
      ankyloglossia with mandibular incisor irregularity and occlusion types. A
      significant positive correlation was determined between the length of the lingual
      frenulum length and mandibular incisor irregularity. There were significant
      positive correlations between the lingual frenulum length, incisor irregularity
      and age. CONCLUSION: Mild and moderate types of ankyloglossia are unrelated to
      mandibular incisor crowding and occlusion type.

PMID- 24914433
TI  - Macroecology of methane-oxidizing bacteria: the beta-diversity of pmoA genotypes
      in tropical and subtropical rice paddies.
AB  - Studies addressing microbial biogeography haveincreased during the past decade,
      but research onmicrobial distribution patterns is still in its infancies,and many
      aspects are only poorly understood. Here,we compared the methanotroph community
      in paddysoils sampled in Indonesia, Vietnam, China and Italy,focusing on the
      distance-decay relationship.We usedthe pmoA gene as marker for methanotroph
      diversityin terminal restriction fragment length polymorphism,microarray and
      pyrosequencing approaches. Wecould observe a significant increase of beta
      diversity with geographical distance across continents (12 000 km).Measured
      environmental parameters explained only asmall amount of data variation, and we
      found no evidencefor dispersal limitation. Thus, we propose
      historicalcontingencies being responsible for theobserved patterns. Furthermore,
      we performed anin-depth analysis of type II methanotroph pmoA distributionat the
      sequence level. We used ordinationanalysis to project sequence dissimilarities
      into athree-dimensional space (multidimensional scaling).The ordination suggests
      that type II methanotrophs inpaddy fields can be divided into five major
      groups.However, these groups were found to be distributed inall soils independent
      of the geographic origin. Byincluding tropical field sites (Indonesia and
      Vietnam)into the analysis, we further observed the firstpaddy fields harbouring a
      methanotroph communitydepleted in type II methanotrophs.

PMID- 24914435
TI  - Selective autophagy goes exclusive.
AB  - Using in vitro reconstitution systems, three studies shed light on the
      interactions of Atg8 family proteins with cargo receptors and components of the
      basal autophagy machinery. The results have important mechanistic implications
      for selective macroautophagy, scaffold formation and spatio-temporal organization
      of the lipidation process during autophagosome formation.

PMID- 24914436
TI  - Integrin beta3 links therapy resistance and cancer stem cell properties.
AB  - Heterogeneity in tumour cell properties underlies many treatment failures.
      Understanding the sources of such heterogeneity has proved to be challenging, but
      remains critical to improving patient outcomes. Integrin alpha(v)beta3 expression
      in multiple types of solid tumour stem cells is now shown to control a pro
      survival pathway that contributes to therapy resistance.

PMID- 24914437
TI  - Vets' perceived role of stress in common feline diseases.

PMID- 24914434
TI  - Mitotic spindle multipolarity without centrosome amplification.
AB  - Mitotic spindle bipolarity is essential for faithful segregation of chromosomes
      during cell division. Multipolar spindles are often seen in human cancers and are
      usually associated with supernumerary centrosomes that result from centrosome
      overduplication or cytokinesis failure. A less-understood path to multipolar
      spindle formation may arise due to loss of spindle pole integrity in response to
      spindle and/or chromosomal forces. Here we discuss the different routes leading
      to multipolar spindle formation, focusing on spindle multipolarity without
      centrosome amplification. We also present the distinct and common features
      between these pathways and discuss their therapeutic implications.

PMID- 24914439
TI  - A flexible approach in Scottish hospitals is making visitors feel welcome on the
      wards.

PMID- 24914438
TI  - Re: Long-term survival of participants in the Prostate Cancer Prevention Trial.

PMID- 24914440
TI  - Watching closely?

PMID- 24914441
TI  - Image of the month: Hypertrophic gastric mucosa heterotopia in cervical
      esophagus.

PMID- 24914442
TI  - Seeing the potential.

PMID- 24914443
TI  - Reply: To PMID 24117484.

PMID- 24914444
TI  - Legionella pneumophila. Preface.

PMID- 24914445
TI  - EndoCAS (center for computer-assisted surgery).

PMID- 24914446
TI  - Super-resolution biological microscopy using virtual imaging by a microsphere
      nanoscope.

PMID- 24914447
TI  - Evaluating the effects of carbon nanoreactor diameter and internal structure on
      the pathways of the catalytic hydrosilylation reaction.
AB  - Three different types of carbon nanoreactors, double-walled nanotubes (DWNT),
      multi-walled nanotubes (MWNT) and graphitised carbon nanofibers (GNF) have been
      appraised for the first time as containers for the reactions of phenylacetylene
      hydrosilylation catalysed by a confined molecular catalyst [Rh4(CO)12].
      Interactions of [Rh4(CO)12] with carbon nanoreactors determining the ratio of
      beta-addition products are unchanged for all nanoreactors and are virtually
      unaffected by the confinement of [Rh4(CO)12] inside carbon nanostructures.
      Conversely, the relative concentrations of reactants affecting the ratio of
      addition and dehydrogenative silylation products is very sensitive to nanoscale
      confinement, with all nanoreactors demonstrating significant effects on the
      distribution of reaction products as compared to control experiments with the
      catalyst in bulk solution or adsorbed on the outer surface of nanoreactors.
      Surprisingly, the widest nanoreactors (GNF) change the reaction pathway most
      significantly, which is attributed to the graphitic step-edges inside GNF
      providing effective anchoring points for the catalyst and creating local
      environments with greatly altered concentrations of reactants as compared to bulk
      solution. Possessing diameters significantly wider than molecules, GNF impose no
      restrictions on the transfer of reactants while providing the strongest
      confinement effects for the reaction. Furthermore, GNF facilitate the effective
      recyclability of the catalyst and thus represents a superior nanoreactor system
      to carbon nanotubes.

PMID- 24914448
TI  - Structure of arginine overlayers at the aqueous gold interface: implications for
      nanoparticle assembly.
AB  - Adsorption of small biomolecules onto the surface of nanoparticles offers a novel
      route to generation of nanoparticle assemblies with predictable architectures.
      Previously, ligand-exchange experiments on citrate-capped gold nanoparticles with
      the amino acid arginine were reported to support linear nanoparticle assemblies.
      Here, we use a combination of atomistic modeling with experimental
      characterization to explore aspects of the assembly hypothesis for these systems.
      Using molecular simulation, we probe the structural and energetic characteristics
      of arginine overlayers on the Au(111) surface under aqueous conditions at both
      low- and high-coverage regimes. In the low-density regime, the arginines lie flat
      on the surface. At constant composition, these overlayers are found to be lower
      in energy than the densely packed films, although the latter case appears
      kinetically stable when arginine is adsorbed via the zwitterion group, exposing
      the charged guanidinium group to the solvent. Our findings suggest that
      zwitterion-zwitterion hydrogen bonding at the gold surface and minimization of
      the electrostatic repulsion between adjacent guanidinium groups play key roles in
      determining arginine overlayer stability at the aqueous gold interface. Ligand
      exchange experiments of citrate-capped gold nanoparticles with arginine
      derivatives agmatine and N-methyl-l-arginine reveal that modification at the
      guanidinium group significantly diminishes the propensity for linear assembly of
      the nanoparticles. 

PMID- 24914449
TI  - Using confined self-adjusting carbon nanotube arrays as high-sensitivity
      displacement sensing element.
AB  - Displacement sensing is a fundamental process in mechanical sensors such as force
      sensors, pressure sensors, accelerometers, and gyroscopes. Advanced techniques
      utilizing nanomaterials have attracted considerable attention in the drive to
      enhance the process. In this paper, we propose a novel and highly sensitive
      device for detecting small displacements. The device utilizes the changes in
      contact resistance between two sets of vertically aligned carbon nanotube (CNT)
      arrays, the growth of which was confined to enable their facile and reliable
      integration with fully fabricated microstructures. Using the displacement
      transduction of the proposed device, we successfully demonstrated a 3-axis wide
      bandwidth accelerometer, which was experimentally confirmed to be highly
      sensitive compared to conventional piezoresistive sensors. Through a test
      involving 1.2 million cycles of displacement transductions, the contact
      resistance of the CNT arrays was proved to be excellently stable, which was a
      consequence of the high electrical stability and mechanical durability of the
      CNTs. 

PMID- 24914450
TI  - Kbeta mainline X-ray emission spectroscopy as an experimental probe of metal
      ligand covalency.
AB  - The mainline feature in metal Kbeta X-ray emission spectroscopy (XES) has long
      been recognized as an experimental marker for the spin state of the metal center.
      However, even within a series of metal compounds with the same nominal oxidation
      and spin state, significant changes are observed that cannot be explained on the
      basis of overall spin. In this work, the origin of these effects is explored,
      both experimentally and theoretically, in order to develop the chemical
      information content of Kbeta mainline XES. Ligand field expressions are derived
      that describe the behavior of Kbeta mainlines for first row transition metals
      with any d(n) count, allowing for a detailed analysis of the factors governing
      mainline shape. Further, due to limitations associated with existing
      computational approaches, we have developed a new methodology for calculating
      Kbeta mainlines using restricted active space configuration interaction (RAS-CI)
      calculations. This approach eliminates the need for empirical parameters and
      provides a powerful tool for investigating the effects that chemical environment
      exerts on the mainline spectra. On the basis of a detailed analysis of the
      intermediate and final states involved in these transitions, we confirm the known
      sensitivity of Kbeta mainlines to metal spin state via the 3p-3d exchange
      coupling. Further, a quantitative relationship between the splitting of the Kbeta
      mainline features and the metal-ligand covalency is established. Thus, this study
      furthers the quantitative electronic structural information that can be extracted
      from Kbeta mainline spectroscopy. 

PMID- 24914452
TI  - The inverse trans influence in a family of pentavalent uranium complexes.
AB  - Systematic ligand variation in a structurally conserved framework of pentavalent
      uranium complexes of the formulas U(V)X2[N(SiMe3)2]3 (X = F, Cl, Br, N3, NCS, 2
      naphthoxide) and U(V)OX[N(SiMe3)2]3(-) (X = -CCPh, -CN) allowed an investigation
      into the role of the inverse trans influence in pentavalent uranium complexes.
      The -CCPh and -CN derivatives were only stable in the presence of the trans-U?O
      multiple bond, implicating the inverse trans influence in stabilizing these
      complexes. Spectroscopic, structural, and density functional theory calculated
      electronic structural data are explored. Near-IR data of all complexes is
      presented, displaying vibronic coupling of 5f(1) electronic transitions along the
      primary axis. Electrochemical characterization allowed assessment of the relative
      donating ability of the various axial ligands in this framework. Electron
      paramagnetic resonance data presented display axial spectra, with hyperfine
      coupling along the primary axis. 

PMID- 24914451
TI  - Enzyme-sensing chitosan hydrogels.
AB  - We report on a chitosan hydrogel-based platform for the detection of enzymes,
      which is compatible with the implementation in infection-sensing wound dressings.
      Thin films of the established wound dressing biopolymer chitosan were
      functionalized with a fluorogenic substrate, which is released upon enzymatic
      degradation, resulting in a pronounced increase in fluorescence emission
      intensity. In this first model study, the fluorogenic substrate alanyl-alanyl
      phenylalanine-7-amido-4-methylcoumarin (AAP-AMC) was covalently conjugated via
      amide bond formation to chitosan and was shown to facilitate the detection of the
      serine protease alpha-chymotrypsin. Systematic investigations established the
      dependence of hydrogel thickness and substrate loading on the hydrogel
      preparation conditions, as well as the dependence of the rate of the reaction on
      the initial enzyme concentration and the loading of AAP-AMC in the hydrogel. The
      initial release rate of the fluorophore 7-AMC was found to be linear with enzyme
      concentration and substrate loading and was independent of hydrogel thickness.
      Under optimized conditions the hydrogel reports the presence of alpha
      chymotrypsin in <5 min with a limit of detection of <=10 nM. This generic
      approach, which can be adapted to detect different kinds of enzymes by using
      appropriate fluorogenic or chromogenic substrates, is highly interesting for
      targeting the detection of specific pathogenic bacteria, e.g., in wound
      dressings. 

PMID- 24914453
TI  - Strategy integrating stepped fragmentation and glycan diagnostic ion-based
      spectrum refinement for the identification of core fucosylated glycoproteome
      using mass spectrometry.
AB  - Core fucosylation (CF) is a special glycosylation pattern of proteins that has a
      strong relationship with cancer. The Food and Drug Administration (FDA) has
      approved the core fucosylated alpha-fetoprotein as a biomarker for the early
      diagnosis of hepatocellular carcinoma (HCC). The technology for identifying core
      fucosylated proteins has significant practical value. The major method for core
      fucosylated glycoprotein/glycopeptide analysis is neutral loss-based MS(3)
      scanning under collision-induced dissociation (CID) by ion trap mass
      spectrometry. However, due to the limited speed and low resolution of the MS(3)
      scan mode, it is difficult to achieve high-throughput, with only dozens of core
      fucosylated proteins identified in a single run. In this work, we developed a
      novel strategy for the identification of CF glycopeptides at a large scale,
      integrating the stepped fragmentation function, one novel feature of quadrupole
      orbitrap mass spectrometry, with "glycan diagnostic ion"-based spectrum
      optimization. By using stepped fragmentation, we were able to obtain both highly
      accurate glycan and peptide information of a simplified CF glycopeptide in one
      spectrum. Moreover, the spectrum could be recorded with the same high speed as
      the conventional MS(2) scan. By using the "glycan diagnostic ion"-based spectrum
      refinement method, the efficiency of the CF glycopeptide discovery was
      significantly improved. We demonstrated the feasibility and reproducibility of
      our method by analyzing CF glycoproteomes of mouse liver tissue and HeLa cell
      samples spiked with standard CF glycoprotein. In total, 1364 and 856 CF
      glycopeptides belonging to 702 and 449 CF glycoproteins were identified,
      respectively, within a 78-min gradient analysis, which was approximately a 7-fold
      increase in the identification efficiency of CF glycopeptides compared to the
      currently used method. In this work, we took core fucosylated glycopeptides as a
      practical example to demonstrate the great potential of our novel method for use
      in glycoproteome analysis, and we also anticipate using the flexible novel method
      in other research fields. 

PMID- 24914454
TI  - The potential of cellulose nanocrystals in tissue engineering strategies.
AB  - Cellulose nanocrystals (CNCs) are a renewable nanosized raw material that is
      drawing a tremendous level of attention from the materials community. These rod
      shaped nanocrystals that can be produced from a variety of highly available and
      renewable cellulose-rich sources are endowed with exceptional physicochemical
      properties which have promoted their intensive exploration as building blocks for
      the design of a broad range of new materials in the past few decades. However,
      only recently have these nanosized substrates been considered for bioapplications
      following the knowledge on their low toxicity and ecotoxicological risk. This
      Review provides an overview on the recent developments on CNC-based functional
      biomaterials with potential for tissue engineering (TE) applications, focusing on
      nanocomposites obtained through different processing technologies usually
      employed in the fabrication of TE scaffolds into various formats, namely, dense
      films and membranes, hierarchical three-dimensional (3D) porous constructs
      (micro/nanofibers mats, foams and sponges), and hydrogels. Finally, while
      highlighting the major achievements and potential of the reviewed work on
      cellulose nanocrystals, alternative applications for some of the developed
      materials are provided, and topics for future research to extend the use of CNCs
      based materials in the scope of the TE field are identified. 

PMID- 24914455
TI  - Maximizing diversity from a kinase screen: identification of novel and selective
      pan-Trk inhibitors for chronic pain.
AB  - We have identified several series of small molecule inhibitors of TrkA with
      unique binding modes. The starting leads were chosen to maximize the structural
      and binding mode diversity derived from a high throughput screen of our internal
      compound collection. These leads were optimized for potency and selectivity
      employing a structure based drug design approach adhering to the principles of
      ligand efficiency to maximize binding affinity without overly relying on
      lipophilic interactions. This endeavor resulted in the identification of several
      small molecule pan-Trk inhibitor series that exhibit high selectivity for
      TrkA/B/C versus a diverse panel of kinases. We have also demonstrated efficacy in
      both inflammatory and neuropathic pain models upon oral dosing. Herein we
      describe the identification process, hit-to-lead progression, and binding
      profiles of these selective pan-Trk kinase inhibitors. 

PMID- 24914456
TI  - Nanoparticle-based detection of oxidized phospholipids by MALDI mass
      spectrometry: nano-MALDI approach.
AB  - In this paper we present a pioneering approach exploiting nanoparticles (NPs) for
      the "on-probe" (i.e., directly from the NP-surface) monitoring of OxPLs by MALDI
      MS (i.e., the Nano-MALDI approach). The "electrophilic interaction" with either
      metal oxide (e.g., ZrO2) or surface-functionalized Fe3O4 core-shell
      superparamagnetic NPs (100 nm diameter) was exploited for the direct enrichment
      of short-chain carboxylic (CARBO)-OxPLs, whereas detection of aldehydic (ALDO)
      OxPLs was enabled by prior derivatization with bifunctional carbonyl-reactive
      reagents containing a negatively charged moiety (e.g., 4-AA) followed by NP
      binding. Polyetheramine (PEA)-NPs were found best suited in terms of solvent
      stability, binding efficiency and compatibility with MALDI-MS analysis. For
      quantitative analysis of the OxPLs a recently introduced MALDI-QIT-TOF-MS/MS
      platform (Stubiger et al. Atherosclerosis 2012, 224, 177-186) was employed and
      cross-validated by LC-ESI-SRM-MS/MS. The sensitivity was found in the sub
      nanomolar range (LOD ~200 pM), which is 1-4 orders of magnitude higher than
      necessary for detection of individual OxPLs under normal and diseased conditions
      in vivo (e.g., in mouse plasma or human lipoproteins). Consequently, the Nano
      MALDI approach shows the potential to serve as novel platform for the screening
      of OxPLs in biological samples and the development of clinical diagnostic tests
      in the future.

PMID- 24914457
TI  - Maximising the value of combining qualitative research and randomised controlled
      trials in health research: the QUAlitative Research in Trials (QUART) study--a
      mixed methods study.
AB  - BACKGROUND: Researchers sometimes undertake qualitative research with randomised
      controlled trials (RCTs) of health interventions. OBJECTIVES: To systematically
      explore how qualitative research is being used with trials and identify ways of
      maximising its value to the trial aim of providing evidence of effectiveness of
      health interventions. DESIGN: A sequential mixed methods study with four
      components. METHODS: (1) Database search of peer-reviewed journals between
      January 2008 and September 2010 for articles reporting the qualitative research
      undertaken with specific trials, (2) systematic search of database of registered
      trials to identify studies combining qualitative research and trials, (3) survey
      of 200 lead investigators of trials with no apparent qualitative research and (4)
      semistructured telephone interviews with 18 researchers purposively sampled from
      the first three methods. RESULTS: Qualitative research was undertaken with at
      least 12% of trials. A large number of articles reporting qualitative research
      undertaken with trials (n=296) were published between 2008 and 2010. A total of
      28% (82/296) of articles reported qualitative research undertaken at the pre
      trial stage and around one-quarter concerned drugs or devices. The articles
      focused on 22 aspects of the trial within five broad categories. Some focused on
      more than one aspect of the trial, totalling 356 examples. The qualitative
      research focused on the intervention being trialled (71%, 254/356), the design
      and conduct of the trial (15%, 54/356), the outcomes of the trial (1%, 5/356),
      the measures used in the trial (3%, 10/356), and the health condition in the
      trial (9%, 33/356). The potential value of the qualitative research to the trial
      endeavour included improving the external validity of trials and facilitating
      interpretation of trial findings. This value could be maximised by using
      qualitative research more at the pre-trial stage and reporting findings with
      explicit attention to the implications for the trial endeavour. During
      interviews, three models of study were identified: qualitative research as
      peripheral to the trial, qualitative research as an 'add-on' to the trial and a
      study with qualitative research and trial as essential components, with the third
      model offering more opportunity to maximise the value of the qualitative
      research. Interviewees valued the use of qualitative research with trials and
      identified team structures and wider structural issues which gave more value to
      the trial than the qualitative research as barriers to maximising the value of
      the qualitative research. CONCLUSION: A large number of articles were published
      between 2008 and 2010, addressing a wide range of aspects of trials. There were
      examples of this research affecting the trial by facilitating interpretation of
      trial findings, developing and refining interventions for testing in the trial
      and changing the measures used in the trial. However, researchers were not
      necessarily maximising the value of qualitative research undertaken with trials
      to the endeavour of generating evidence of effectiveness of health interventions.
      Researchers can maximise value by promoting its use at the pre-trial stage to
      ensure that the intervention and trial conduct is optimised at the main trial
      stage, being explicit about the conclusions for the trial endeavour in peer
      reviewed journal articles reporting the qualitative research and valuing the
      contribution of the qualitative research as much as the trial. Future
      recommendations for researchers include: plan the qualitative research, design
      and implement studies not trials, use qualitative research at the feasibility and
      pilot stage of trials, be explicit in publications about the impact of the
      qualitative research on the trial and implications for the trial endeavour,
      undertake in-depth qualitative research, allow qualitative research to take a
      challenging role and develop a learning environment around the use of qualitative
      research and trials. FUNDING: This project was funded by the Medical Research
      Council (MRC) as part of the MRC-National Institute for Health Research
      Methodology Research programme.

PMID- 24914458
TI  - Medical errors and uncertainty in primary healthcare: a comparative study of
      coping strategies among young and experienced GPs.
AB  - OBJECTIVE: To study coping differences between young and experienced GPs in
      primary care who experience medical errors and uncertainty. DESIGN: Questionnaire
      based survey (self-assessment) conducted in 2011. SETTING: Finnish primary
      practice offices in Southern Finland. SUBJECTS: Finnish GPs engaged in primary
      health care from two different respondent groups: young (working experience <= 5
      years, n = 85) and experienced (working experience > 5 years, n = 80). MAIN
      OUTCOME MEASURES: Outcome measures included experiences and attitudes expressed
      by the included participants towards medical errors and tolerance of uncertainty,
      their coping strategies, and factors that may influence (positively or
      negatively) sources of errors. RESULTS: In total, 165/244 GPs responded (response
      rate: 68%). Young GPs expressed significantly more often fear of committing a
      medical error (70.2% vs. 48.1%, p = 0.004) and admitted more often than
      experienced GPs that they had committed a medical error during the past year
      (83.5% vs. 68.8%, p = 0.026). Young GPs were less prone to apologize to a patient
      for an error (44.7% vs. 65.0%, p = 0.009) and found, more often than their more
      experienced colleagues, on-site consultations and electronic databases useful for
      avoiding mistakes. CONCLUSION: Experienced GPs seem to better tolerate
      uncertainty and also seem to fear medical errors less than their young
      colleagues. Young and more experienced GPs use different coping strategies for
      dealing with medical errors. IMPLICATIONS: When GPs become more experienced, they
      seem to get better at coping with medical errors. Means to support these skills
      should be studied in future research.

PMID- 24914459
TI  - Prevalence of metabolic syndrome among antiretroviral-naive and antiretroviral
      experienced HIV-1 infected Thai adults.
AB  - Metabolic syndrome (MS), a group of interrelated risk factors for cardiovascular
      diseases (CVD) and type 2 diabetes, has been increasingly reported among HIV
      infected patients. Data on the prevalence and risk factors for MS among HIV-1
      infected Thai adults are limited. The study collected cross-sectional data from
      580 HIV-1 infected adults-46.2% were men and 71% were antiretroviral therapy
      (ART)-experienced. The majority (78.8%) of them used non-nucleoside reverse
      transcriptase inhibitor-based regimens. Data on lipid profiles, fasting blood
      glucose, CD4 count, HIV RNA, antiretroviral therapy (ART), anthropometry, food
      intake, and exercise were recorded. MS was defined using American Heart
      Association/National Heart Lung and Blood Institute criteria. Overall prevalence
      of MS was 22.2%; 15.9% in ART-naive group vs. 24.9% in ART-experienced group, p =
      0.018. Significant risk factors for MS in multivariate analyses included age >=35
      years (odds ratio, OR, 4.2, 95%CI 1.6-11.0, p = 0.004), high cholesterol (OR 4.7,
      95%CI 1.7-12.9, p = 0.002), and living outside Bangkok (OR 4.2, 95%CI 1.6-10.8, p
      = 0.003) in the ART-naive group, and female gender (OR 1.7, 95%CI 1.0-2.8, p =
      0.05), lipodystrophy (OR 1.8, 95%CI 1.0-3.0, p = 0.032), high cholesterol (OR
      1.9, 95%CI 1.1-3.1, p = 0.015), and food insecurity (OR 1.8, 95%CI 1.0-3.3, p =
      0.05) in the ART-experienced group. All variables, except for female gender in
      the ART-experienced group, remained significantly associated with MS in a model
      where lipodystrophy was excluded. We concluded that MS was common among HIV-1
      infected Thai adults. As HIV-infected patients get older, early screening and
      intervention, such as ART modification to avoid lipodystrophy, may reduce MS and
      CVD-related morbidities and mortalities in long-term care.

PMID- 24914460
TI  - Neuroticism and self-evaluation measures are related to the ability to form
      cognitive maps critical for spatial orientation.
AB  - Trait neuroticism is suggested to be related to measures of volume and function
      of the hippocampus, a brain structure located in the medial temporal lobe that is
      critical for human navigation and orientation. In this study, we assessed whether
      measures of trait neuroticism and self-concept are correlated with the human
      ability to orient by means of cognitive maps (i.e. mental representations of an
      environment that include landmarks and their spatial relationships). After
      controlling for gender differences, which are well-known in spatial orientation
      abilities, we found that measures of neuroticism (i.e. negative affect, emotional
      stability) and self-concept (i.e. self-esteem) were correlated with individual
      differences in the rate at which cognitive maps were formed; the same measures
      were generally unrelated to the ability to make use of cognitive maps, as well as
      the ability to orient using visual path integration. The relationships (and lack
      thereof) between personality traits and the spatial orientation skills, as
      reported in the present study, are consistent with specific neural correlates
      underlying these factors, and may have important implications for treatment of
      disorders related to them. 

PMID- 24914461
TI  - Effects of curcumin on learning and memory deficits, BDNF, and ERK protein
      expression in rats exposed to chronic unpredictable stress.
AB  - Accumulating evidence suggests that cognitive processes, such as learning and
      memory, are affected in depression and antidepressant treatment may ameliorate
      cognitive impairments. Recent studies have shown that curcumin exhibits
      antidepressant-like effects. The aim of the present study was to determine
      whether curcumin administration influences chronic unpredictable stress (CUS)
      induced cognitive deficits and explores underlying mechanisms. Male Wistar rats
      were subjected to CUS protocol for a period of 5 weeks to induce depression. The
      depressive-like behavior was tested using sucrose preference test, open field
      test and Morris water maze test. Effects of curcumin on brain-derived
      neurotrophic factor (BDNF) and extracellular signal-regulated kinase (ERK) levels
      in the hippocampus were also examined. Chronic treatment with curcumin
      significantly reversed the CUS-induced behavioral and cognitive parameters
      (reduced sucrose preference and impaired learning and memory function) in
      stressed rats. Additionally, CUS reduced hippocampal BDNF and ERK levels, while
      curcumin effectively reversed these alterations. Taken together, our results
      indicate that the antidepressant-like effects of curcumin in CUS rats are related
      to its aptitude to promote BDNF and ERK in the hippocampus. 

PMID- 24914462
TI  - Examination of the role of dopamine D2 and adrenergic alpha2 receptors in
      resurgence of food seeking.
AB  - Resurgence refers to the reappearance of an extinguished operant behavior when
      reinforcement for an alternative behavior is also subsequently discontinued.
      Resurgence has been noted as a source of relapse to problem behavior following
      interventions involving alternative reinforcement, and has also been recently
      used as an animal model of relapse to drug seeking induced by reinforcement loss.
      Existing information about the neuropharmacology of resurgence is scarce, but
      suggests overlap between relapse observed in the resurgence model and relapse
      observed in reinstatement and renewal models. In the present experiment rats
      earned food pellets for pressing a target lever in Phase I. In Phase II lever
      pressing no longer produced food, but food was delivered for an alterative nose
      poke response. Finally in Phase III, neither response produced food deliveries.
      Prior to these Phase III sessions, separate groups of rats were injected with 0,
      50, or 100 MUg/kg of the dopamine D2 receptor antagonist raclopride or 0, 20, or
      40 MUg/kg of alpha 2 agonist clonidine. Both doses of raclopride were effective
      in blocking resurgence, but there was evidence that the higher dose did so via
      motor rather than motivational impairment. Only the higher dose of clonidine
      blocked resurgence, but did so with no evidence of motor impairment. Raclopride
      significantly impacted extinction of the alternative poke at both doses tested,
      whereas clonidine had no effect at either dose. The results of the present study
      provide additional information about the neuropharmacology of resurgence, as well
      as additional evidence of overlap between resurgence, reinstatement, and renewal.

PMID- 24914465
TI  - Thermal diffusion desorption for the comprehensive analysis of organic compounds.
AB  - Comprehensive analysis of organic compounds is crucial yet challenging
      considering that information on elements, fragments, and molecules is unavailable
      simultaneously by current analytical techniques. Additionally, many compounds are
      insoluble or only dissolve in toxic solvents. A solvent- and matrix-free strategy
      has been developed which allows the organic compound analyzed in its original
      form. It utilizes thermal diffusion desorption with the solid analyte irradiated
      with high energy laser. It is capable of providing explicit elemental,
      fragmental, and molecular information simultaneously for a variety of organic
      compounds. Thermal diffusion desorption has many advantages compared to the
      electrospray and MALDI techniques. The protons that form the protonated molecular
      ions originate from the analyte itself. All the elements and fragments are also
      derived from the analyte itself, which provides abundant information and
      expedites the identification of organic compounds. 

PMID- 24914463
TI  - Anticipatory 50 kHz ultrasonic vocalizations are associated with escalated
      alcohol intake in dependent rats.
AB  - Rats emit 50kHz ultrasonic vocalizations (USVs) in situations of increased
      motivation, such as during the anticipation of palatable food or drugs of abuse.
      Whether the same holds true for the anticipation of alcohol intake remains
      unknown. Alcohol drinking in a nondependent state is thought to be mediated by
      its rewarding effects (positive reinforcement), whereas drinking in the dependent
      state is motivated by alcohol's stress-relieving effects (negative
      reinforcement). Here, we measured context-elicited 50kHz USVs in alcohol
      dependent (alcohol vapor-exposed) and nondependent rats immediately before
      operant alcohol self-administration sessions. Dependent rats showed escalated
      levels of alcohol intake compared with nondependent rats. Overall, dependent and
      nondependent rats showed similar levels of anticipatory 50kHz USVs. However, the
      number of anticipatory USVs was positively correlated with alcohol intake in
      dependent rats but not nondependent rats. Additionally, dependent rats with
      higher alcohol intake displayed increased anticipatory 50kHz USVs compared with
      rats that had lower alcohol intake, whereas no difference was observed between
      rats with high and low alcohol intake in the nondependent group. Increased 50kHz
      USVs were specific for the anticipation of alcohol self-administration and did
      not generalize to a novel environment. These findings suggest that anticipatory
      50kHz USVs may be an indicator of context-elicited negative reinforcement
      learning.

PMID- 24914464
TI  - Total body irradiation is permissive for mesenchymal stem cell-mediated new bone
      formation following local transplantation.
AB  - Skeletal injury is a major clinical challenge accentuated by the decrease of bone
      marrow-derived mesenchymal stem/stromal cells (BMSCs) with age or disease.
      Numerous experimental and clinical studies have revealed that BMSCs hold great
      promise for regenerative therapies due to their direct osteogenic potential and
      indirect trophic/paracrine actions. Increasing evidence suggests that stromal
      cell-derived factor-1 (SDF-1) is involved in modulating the host response to the
      injury. Common problems with BMSC therapy include poor cell engraftment, which
      can be addressed by total body irradiation (TBI) prior to transplantation. In
      this study, we tested the hypothesis that direct tibial transplantation of BMSCs
      drives endogenous bone formation in a dose-dependent manner, which is enhanced by
      TBI, and investigated the potential role of SDF-1 in facilitating these events.
      We found that TBI is permissive for transplanted BMSCs to engraft and contribute
      to new bone formation. Bone marrow (BM) interstitial fluid analysis revealed no
      differences of SDF-1 splice variants in irradiated animals compared to controls,
      despite the increased mRNA and protein levels expressed in whole BM cells. This
      correlated with increased dipeptidyl peptidase IV activity and the failure to
      induce chemotaxis of BMSCs in vitro. We found increased mRNA expression levels of
      the major SDF-1-cleaving proteases in whole BM cells from irradiated animals
      suggesting distinct spatial differences within the BM in which SDF-1 may play
      different autocrine and paracrine signaling roles beyond the immediate cell
      surface microenvironment. 

PMID- 24914466
TI  - Methylxanthine reversal of opioid-induced respiratory depression in the neonatal
      rat: mechanism and location of action.
AB  - Methylxanthines like caffeine and theophylline have long been used to treat apnea
      of prematurity. Despite their success in stimulating neonatal breathing, their
      mechanism of action remains poorly understood. Methylxanthines can act as both
      non-specific adenosine receptor antagonists and inhibitors of cAMP-dependent
      phosphodiesterases, sarcoplasmic/endoplasmic reticulum calcium ATPases or
      receptor-coupled anion channels, depending on the dose used. Though there is
      evidence for methylxanthine action at the level of the carotid body, the
      consensus is that methylxanthines stimulate the respiratory centers of the
      brainstem. Here we used the in situ neonatal rat working heart-brainstem
      preparation and the ex vivo neonatal rat carotid body preparation to test the
      hypothesis that methylxanthines act at the level of the carotid body. We conclude
      that although the neonatal carotid body has active adenosine receptors, the
      effects of methylxanthine therapy are likely mediated centrally, predominantly
      via inhibition of cAMP-dependent phosphodiesterase-4. 

PMID- 24914467
TI  - Post-natal hypoxic activity of the central respiratory command is improved in
      transgenic mice overexpressing Epo in the brain.
AB  - Previous studies indicated that erythropoietin modulates central respiratory
      command in mice. Specifically, a one-hour incubation of the brainstems with
      erythropoietin attenuates hypoxia-induced central respiratory depression. Here,
      using transgenic mice constitutively overexpressing erythropoietin specifically
      in the brain (Tg21), we investigated the effect of chronic erythropoietin
      stimulation on central respiratory command activity during post-natal
      development. In vitro brainstem-spinal cord preparations from mice at 0 (P0) or 3
      days of age (P3) were used to record the fictive inspiratory activity from the C4
      ventral root. Our results show that erythropoietin already stimulates the hypoxic
      burst frequency at P0, and at P3, erythropoietin effectively stimulates the
      hypoxic burst frequency and amplitude. Because the maturation of the central
      respiratory command in mice is characterized by a decrease in the burst frequency
      with age, our results also suggest that erythropoietin accelerates the maturation
      of the newborn respiratory network and its response to hypoxia. 

PMID- 24914468
TI  - Short-term effect of crural fasciotomy on kinematic variability and propulsion
      during level locomotion.
AB  - Treadmill locomotion can be characterized by consistent step-to-step kinematics
      despite the redundant degrees of freedom. The authors investigated the effect of
      disrupting the crural fascia in decerebrate cats to determine if the crural
      fascia contributed to kinematic variability and propulsion in the limb. Crural
      fasciotomy resulted in statistically significant decreases in velocity and
      acceleration in the joint angles during level walking, before, during, and after
      paw-off, particularly at the ankle. A further finding was an increase in variance
      of the limb segment trajectories in the frontal plane. The crural fascia
      therefore provides force transmission and reduction in kinematic variability to
      the limb during locomotion.

PMID- 24914469
TI  - Synthesis, characterization, and photophysical and electroluminescent properties
      of blue-emitting cationic iridium(III) complexes bearing nonconjugated ligands.
AB  - The development of pure-blue-to-deep-blue-emitting ionic phosphors is an ultimate
      challenge for full-color displays and white-light sources. Herein we report two
      series of short-wavelength light-emitting cationic iridium(III) complexes with
      nonconjugated ancillary and cyclometalating ligands, respectively. In the first
      series, nonconjugated 1-[(diphenylphosphino)methyl]-3-methylimidazolin-2-ylidene
      C,C2' (dppmmi) is used as the ancillary ligand and 2-phenylpyridine (ppy), 2-(2,4
      difluorophenyl)pyridine (dfppy), and 1-(2,4-difluorophenyl)-1H-pyrazole (dfppz)
      are used as cyclometalating ligands. In the second one, nonconjugated 2,4
      difluorobenzyl-N-pyrazole (dfbpz) is used as the cyclometalating ligand and 3
      methyl-1-(2-pyridyl)benzimidazolin-2-ylidene-C,C(2)' (pymbi) as the ancillary
      ligand. The synthesis and photophysical and electrochemical properties, together
      with the X-ray crystal structures of these complexes, have been investigated. At
      room temperature, blue-emitting complexes [Ir(ppy)2(dppmmi)]PF6 (1) and
      [Ir(dfppy)2(dppmmi)]PF6 (2; PF6(-) is hexafluorophosphate) show much larger
      photoluminescence quantum yields of 24% and 46%, respectively. On the contrary,
      for complexes [Ir(dfppz)2(dppmmi)]PF6 (3) and [Ir(dfbpz)2(pymbi)]PF6 (4), deep
      blue luminescence is only observed at low temperature (77 K). Density functional
      theory calculations are used to rationalize the differences in the photophysical
      behavior observed upon changes of the ligands. It is shown that the electronic
      transition dipoles of cationic iridium complexes 1 and 2 are mainly confined to
      cyclometalated ligands ((3)MLCT and LC (3)pi-pi*) and those of complex 3 are
      confined to all of the ligands ((3)MLCT, LC (3)pi-pi*, and (3)LLCT) because of
      the high LUMO energy level of dfppz. The emission of 4 mainly originates from the
      central iridium(III) ion and cyclometalated ligand to ancillary ligand charge
      transfer ((3)MLCT and (3)LLCT), in contrast to commonly designed cationic
      complexes using carbene-type ancillary ligands, where emission originates from
      the cyclometalated main ligands. Solution-processed organic light-emitting diodes
      based on complexes 1 and 2 gave blue-green (498 nm) and blue (478 nm)
      electroluminescence with maximum current efficiencies of 3.8 and 3.4 cd A(-1),
      respectively. The results indicate that introducing nonconjugated ligands into
      cationic iridium complexes is an effective means of achieving short-wavelength
      light-emitting phosphors. 

PMID- 24914470
TI  - Luteolin modulates expression of drug-metabolizing enzymes through the AhR and
      Nrf2 pathways in hepatic cells.
AB  - Drugs, xenobiotics including environmental pollutants, and certain food
      components modulate expression of drug-metabolizing enzymes. An aryl hydrocarbon
      receptor (AhR) possesses possible expression of phase I and phase II enzymes
      directly by binding of its ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and indirectly by regulating expression of nuclear factor-erythroid-2
      related factor 2 (Nrf2). Previous our result demonstrated that luteolin, a
      natural flavonoid existing in vegetables and herbs, competed the binding of TCDD
      to AhR. In the present study, we investigated the effect of luteolin on the
      expression of drug-metabolizing enzymes through the AhR and Nrf2 pathways.
      Luteolin inhibited TCDD-induced protein expression of phase I enzyme cytochrome
      P450 1A1 (CYP1A1), phase II enzymes NAD(P)H: quinone oxidoreductase-1 (NQO1) and
      glutathione-S-transferase P1 (GSTP1) in HepG2, Hepa1c1c7 and RL-34 cells in a
      dose-dependent manner. Luteolin suppressed TCDD- and tert-butylhydroquinone
      induced Nrf2 protein by decreasing its stability in HepG2 cells. In tert
      butylhydroquinone treated cells, luteolin dose-dependently inhibited NQO1, GSTP1
      and aldo-keto reductases (AKRs). Of these, protein expression of CYP1A1 and GSTP1
      was mainly dominated by the AhR pathway, while that of NQO1 and AKRs was by the
      Nrf2 pathway. In conclusion, luteolin inhibits expression of phase I and phase II
      drug-metabolizing enzymes by modulating the AhR and Nrf2 pathways.

PMID- 24914471
TI  - "Footprint-free" human induced pluripotent stem cell-derived astrocytes for in
      vivo cell-based therapy.
AB  - The generation of human induced pluripotent stem cells (hiPSC) from somatic cells
      has enabled the possibility to provide patient-specific hiPSC for cell-based
      therapy, drug discovery, and other translational applications. Two major
      obstacles in using hiPSC for clinical application reside in the risk of genomic
      modification when they are derived with viral transgenes and risk of teratoma
      formation if undifferentiated cells are engrafted. In this study, we report the
      generation of "footprint-free" hiPSC-derived astrocytes. These are efficiently
      generated, have anatomical and physiological characteristics of fully
      differentiated astrocytes, maintain homing characteristics typical of stem cells,
      and do not give rise to teratomas when engrafted in the brain. Astrocytes can be
      obtained in sufficient numbers, aliquoted, frozen, thawed, and used when needed.
      Our results show the feasibility of differentiating astrocytes from "footprint
      free" iPSC. These are suitable for clinical cell-based therapies as they can be
      induced from patients' specific cells, do not require viral vectors, and are
      fully differentiated. "Footprint-free" hiPSC-derived astrocytes represent a new
      potential source for therapeutic use for cell-based therapy, including treatment
      of high-grade human gliomas, and drug discovery. 

PMID- 24914472
TI  - The alpha subunit of nitrile hydratase is sufficient for catalytic activity and
      post-translational modification.
AB  - Nitrile hydratases (NHases) possess a mononuclear iron or cobalt cofactor whose
      coordination environment includes rare post-translationally oxidized cysteine
      sulfenic and sulfinic acid ligands. This cofactor is located in the alpha-subunit
      at the interfacial active site of the heterodimeric enzyme. Unlike canonical
      NHases, toyocamycin nitrile hydratase (TNHase) from Streptomyces rimosus is a
      unique three-subunit member of this family involved in the biosynthesis of
      pyrrolopyrimidine antibiotics. The subunits of TNHase are homologous to the alpha
      and beta-subunits of prototypical NHases. Herein we report the expression,
      purification, and characterization of the alpha-subunit of TNHase. The UV
      visible, EPR, and mass spectra of the alpha-subunit TNHase provide evidence that
      this subunit alone is capable of synthesizing the active site complex with full
      post-translational modifications. Remarkably, the isolated post-translationally
      modified alpha-subunit is also catalytically active with the natural substrate,
      toyocamycin, as well as the niacin precursor 3-cyanopyridine. Comparisons of the
      steady state kinetic parameters of the single subunit variant to the
      heterotrimeric protein clearly show that the additional subunits impart substrate
      specificity and catalytic efficiency. We conclude that the alpha-subunit is the
      minimal sequence needed for nitrile hydration providing a simplified scaffold to
      study the mechanism and post-translational modification of this important class
      of catalysts. 

PMID- 24914473
TI  - Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its
      interaction with ANK3 gene polymorphism.
AB  - Recent studies have shown that bipolar disorder (BPD) and schizophrenia (SZ)
      share some common genetic risk factors. This study aimed to examine the
      association between candidate single nucleotide polymorphisms (SNPs) identified
      from genome-wide association studies (GWAS) and risk of BPD and SZ. A total of
      715 patients (244 BPD and 471 SZ) and 593 controls were genotyped using the
      Sequenom MassARRAY platform. We showed a positive association between LMAN2L
      (rs6746896) and risk of both BPD and SZ in a pooled population (P-value=0.001 and
      0.009, respectively). Following stratification by ethnicity, variants of the ANK3
      gene (rs1938516 and rs10994336) were found to be associated with BPD in Malays (P
      value=0.001 and 0.006, respectively). Furthermore, an association exists between
      another variant of LMAN2L (rs2271893) and SZ in the Malay and Indian ethnic
      groups (P-value=0.003 and 0.002, respectively). Gene-gene interaction analysis
      revealed a significant interaction between the ANK3 and LMAN2L genes (empirical
      P=0.0107). Significant differences were shown between patients and controls for
      two haplotype frequencies of LMAN2L: GA (P=0.015 and P=0.010, for BPD and SZ,
      respectively) and GG (P=0.013 for BPD). Our study showed a significant
      association between LMAN2L and risk of both BPD and SZ. 

PMID- 24914474
TI  - Improving Probabilities of Correct Interim Decision in Population Enrichment
      Designs.
AB  - Choice of target population is an essential part at the design stage of clinical
      trials. Data from earlier clinical development might suggest that the treatment
      is more effective in a subpopulation, but there might not be enough evidence to
      restrict the target population upfront. Adaptive designs allow modification of
      the target population based on interim data. Decision for modification should be
      based on objective decision rules. The presented decision rules maximize the
      weighted probability of correct interim decisions based on prior assumptions.
      Evaluation of decision rules in the planning phase can improve probabilities of
      correct interim decision and power. 

PMID- 24914475
TI  - AlCl3-mediated aldol cyclocondensation of 1,6- and 1,7-diones to cyclopentene and
      cyclohexene derivatives.
AB  - Exactly 1/3 mol of AlCl3 is sufficient to cyclize 1 mol of 1,omega
      dibenzoylbutane (or pentane) to a cyclopentenone (or hexenone) derivative in high
      yield at room temperature in 40 min to several hours. This condensation is driven
      by removing elements of water as HCl and Al(OH)3, and the product enones are
      exclusively unconjugated, unlike the base-catalyzed condensations providing
      thermodynamically more stable conjugated enones. 

PMID- 24914476
TI  - Ranibizumab in preproliferative (ischemic) central retinal vein occlusion: the
      rubeosis anti-VEGF (RAVE) trial.
AB  - PURPOSE: To analyze the efficacy and safety of ranibizumab in eyes with
      preproliferative (ischemic) central retinal vein occlusion. METHODS: In this
      prospective, phase I/II, open-label clinical trial, eyes at high risk of
      neovascular complications were identified; all eyes met >= 3 of 4 high-risk
      criteria: 1) the best-corrected visual acuity being <= 20/200, 2) loss of the 1
      2e isopter on Goldmann visual field, 3) relative afferent pupillary defect being
      >= 0.9 log units, and 4) electroretinogram B-wave reduction to <= 60% of the
      corresponding A-wave. Monthly intravitreal ranibizumab treatment for 9 months,
      monthly monitoring for 3 months, and then monthly examination with pro re nata
      retreatment on evidence of disease activity for 24 months were performed.
      Therefore, the total study duration was 36 months. RESULTS: The main outcome
      measures were mean change in the best-corrected visual acuity and central macular
      thickness by optical coherence tomography, proportion of patients with
      neovascular complications, and the incidence and severity of ocular and nonocular
      adverse events. Twenty patients were enrolled in the Rubeosis Anti-VEgf trial,
      and the mean number of intravitreal treatments administered through Months 24 and
      36 were 14.1 and 17.2, respectively. The mean best-corrected visual acuity
      letters gained were +21.1 and +21.4 at 9 and 36 months, respectively. The mean
      central macular thickness improved -294 MUm from baseline after 9 monthly
      treatments. Subsequently, after 3 months of observation, the mean central macular
      thickness increased +203 MUm. On initiation of pro re nata ranibizumab
      retreatment, the mean central macular thickness then improved -191 MUm at Month
      36 compared with Month 12. Nine patients developed neovascular complications,
      being diagnosed after a mean of 24-month follow-up (range, 3-44 months), with 2
      patients developing neovascularization after completion of the 36-month trial
      endpoint (at Months 42 and 44 after study enrollment). CONCLUSION: Intravitreal
      ranibizumab therapy can improve retinal anatomy and vision in eyes with severe
      central retinal vein occlusion. Despite significant clinical benefit with
      antivascular endothelial growth factor therapy, the risk of neovascular
      complications was not ameliorated by vascular endothelial growth factor blockade,
      but was merely delayed.

PMID- 24914478
TI  - Telomere length regulation in budding yeasts.
AB  - Telomeres are the nucleoprotein caps of chromosomes. Their length must be tightly
      regulated in order to maintain the stability of the genome. This is achieved by
      the intricate network of interactions between different proteins and protein-RNA
      complexes. Different organisms use various mechanisms for telomere length
      homeostasis. However, details of these mechanisms are not yet completely
      understood. In this review we have summarized our latest achievements in the
      understanding of telomere length regulation in budding yeasts. 

PMID- 24914479
TI  - Desvenlafaxine for the treatment of major depressive disorder.
AB  - INTRODUCTION: Major depressive disorder (MDD) is a chronic and debilitating
      condition often characterized by inadequate treatment. Notwithstanding the
      availability of more than a dozen first-line agents across disparate classes
      (e.g., selective serotonin reuptake inhibitors), the majority of individuals with
      MDD do not achieve and sustain a recovered state. A substantial percentage of MDD
      patients require a treatment change due to poor efficacy or tolerability. AREAS
      COVERED: This review focuses on recent (<= 5 years) literature describing the
      pharmacokinetics, efficacy, and tolerability of desvenlafaxine , one of the more
      recently approved antidepressant drugs. Published papers identified via PubMed
      search and congress presentations were included. Results from short-term, placebo
      controlled, MDD trials and randomized withdrawal trials, as well as post hoc
      analyses in patient subgroups, are reviewed. EXPERT OPINION: Desvenlafaxine has
      been shown to be an effective antidepressant with a favorable safety and
      tolerability profile in the general MDD population and in important patient
      subgroups. It has several notable differences from other serotonin-norepinephrine
      reuptake inhibitors, and those differences suggest populations in which it may
      have the most clinical benefit.

PMID- 24914480
TI  - Efficacy of colestilan in the treatment of hyperphosphataemia in renal disease
      patients.
AB  - INTRODUCTION: Hyperphosphataemia is common in chronic kidney disease (CKD),
      particularly in the late stages and is associated with secondary
      hyperparathyroidism, abnormal bone mineralisation and increased cardiovascular
      morbidity/mortality. At present, there is a range of phosphate binders designed
      to keep serum phosphate at normal or near normal levels. Colestilan is a new
      binder that offers additional actions that may afford further benefits over
      simply lowering phosphate. AREAS COVERED: This paper reviews the pharmacology and
      clinical data currently available in the use of colestilan to treat
      hyperphosphataemia in CKD stage 5 patients on dialysis. EXPERT OPINION: Available
      phosphate binders lower serum phosphorus levels to a clinically relevant extent.
      The balance between the risks and the potential benefits associated with each
      agent must be considered when choosing a binder. Calcium-based binders can lead
      to hypercalcaemia and/or positive calcium balance and cardiovascular
      calcification. Like sevelamer, colestilan is not absorbed and there is no
      evidence of any risk of hypercalcaemia. In addition, a significant lowering of
      low-density lipoprotein-cholesterol, similar to simvastatin, a reduction in
      plasma uric acid and a reduction in high glycosylated haemoglobin values suggest
      additional beneficial actions that may convert to reductions in mortality.

PMID- 24914482
TI  - Health-related quality of life and voice following radiotherapy for laryngeal
      cancer--a comparison between glottic and supraglottic tumours.
AB  - BACKGROUND: To provide further information about short-term effects on voice
      quality and health-related quality of life (HRQL) following radiotherapy for
      laryngeal cancer, comparing glottic and supraglottic tumours. MATERIAL AND
      METHODS: Sixty-seven male patients who received radiotherapy for glottic and
      supraglottic tumours were included. Voice recordings were performed and patient
      reported outcome questionnaires filled in before radiotherapy and one-month post
      completion. Acoustic and temporal measures were produced from the recordings and
      compared to an age-matched, vocally healthy control group (n = 23). RESULTS:
      Deterioration of HRQL post-radiotherapy was noted for both the glottic and
      supraglottic cohort. Pre- radiotherapy the glottic cohort demonstrated acoustic
      and temporal measures that were statistically different from healthy controls,
      with improvements post-radiotherapy where several measures showed no
      statistically significant differences compared to healthy controls. The
      supraglottic cohort revealed voice measures comparable to the healthy controls
      but demonstrated statistically significant impairments in HRQL compared to the
      glottic cohort following radiotherapy. CONCLUSION: Patients with supraglottic
      tumours may experience more eating and swallowing related problems prior to
      radiotherapy compared to glottic tumours and demonstrate a more significant
      reduction in HRQL following treatment. However, in terms of voice measurements,
      subjective measures correlate poorly with objective acoustic parameters, thereby
      emphasising the importance of patient-reported outcomes as part of treatment
      evaluation.

PMID- 24914483
TI  - Prescribing and evaluating target dose in dose-painting treatment plans.
AB  - BACKGROUND: Assessment of target dose conformity in multi-dose-level treatment
      plans is challenging due to inevitable over/underdosage at the border zone
      between dose levels. Here, we evaluate different target dose prescription
      planning aims and approaches to evaluate the relative merit of such plans. A
      quality volume histogram (QVH) tool for history-based evaluation is proposed.
      MATERIAL AND METHODS: Twenty head and neck cancer dose-painting plans with five
      prescription levels were evaluated, as well as clinically delivered simultaneous
      integrated boost (SIB) plans from 2010 and 2012. The QVH tool was used for target
      dose comparison between groups of plans, and to identify and improve a suboptimal
      dose-painting plan. RESULTS: Comparison of 2010 and 2012 treatment plans with the
      QVH tool demonstrated that 2012 plans have decreased underdosed volume at the
      expense of increased overdosed volume relative to the 2010 plans. This shift had
      not been detected previously. One suboptimal dose-painting plan was compared to
      the 'normal zone' of the QVH tool and could be improved by re-optimization.
      CONCLUSION: The QVH tool provides a method to assess target dose conformity in
      dose-painting and multi-dose-level plans. The tool can be useful for quality
      assurance of multi-center trials, and for visualizing the development of
      treatment planning in routine clinical practice.

PMID- 24914484
TI  - Incidence and risk of rash to mTOR inhibitors in cancer patients--a meta-analysis
      of randomized controlled trials.
AB  - BACKGROUND: Inhibitors of the mammalian target of rapamycin (mTOR) are currently
      approved for the treatment of several cancers, and their use is associated with
      serious rash, which affects patient's quality of life and leads to undesirable
      dose reductions or interruptions. A meta-analysis of randomized controlled trials
      (RCTs) was performed to determine the overall risk of developing high-grade rash
      with mTOR inhibitors in cancer patients. METHODS: We searched the PubMed database
      and abstracts presented at the American Society of Clinical Oncology (ASCO)
      meetings up to December 2013 for relevant studies. Eligible studies included RCTs
      in which everolimus or temsirolimus was compared to controls in cancer patients.
      The summary incidence, relative risk (RR), and 95% confidence intervals (CI) were
      calculated using a random- or fixed-effects model depending on the heterogeneity
      of the included trials. RESULTS: A total of 11 RCTs with 4752 patients (mTORs:
      2725, controls: 2027) with a variety of solid tumors were included in the
      analysis. The incidences of all-grade (grade 1-4) and high-grade rash (grade 3-4)
      were 27.3% (95% CI 21.0-34.7%) and 1.0% (95% CI 0.6-1.4%), respectively. In
      comparison with controls, mTOR inhibitors significantly increased the risk for
      developing all-grade rash (RR = 3.55, 95% CI 3.0-4.20, p < 0.001) and high-grade
      rash (RR = 4.25, 95% CI 1.63-11.10, p = 0.003). The increased risk of high-grade
      rash did not vary significantly among different tumors (p = 0.91). There was no
      significant difference between everolimus and temsirolimus (p = 0.60). There was
      also no significant difference between mTOR inhibitors alone and in combination
      with other agents (p = 0.57). CONCLUSIONS: Everolimus and temsirolimus
      significantly increased the risk of high-grade rash in cancer patients. Early
      recognition and appropriate treatment is recommended.

PMID- 24914485
TI  - Allopurinol in renal ischemia.
AB  - Allopurinol is a xanthine oxidase inhibitor and antioxidant free radical
      scavenger which facilitates the protection of ischemic organs in part via this
      mechanism of action. The accumulation of free radicals during ischemia and
      reperfusion is in great manner overcome by inhibitors of xanthine oxidase and by
      the development of endogenous antioxidants. The ischemic lesion generates a well
      established inflammatory response with the subsequent production of inflammatory
      molecules characteristically present at the first stages of the injury.
      Inflammatory cytokines, chemokines, adhesion molecules, and other cellular and
      molecular compounds are consequently produced as the lesion sets in. Under these
      conditions, allopurinol diminishes the effect of inflammatory mediators during
      the ischemic inflammatory response. This study reviews the literature associated
      with allopurinol and renal ischemia making special emphasis on the best dose and
      time of administration of allopurinol regarding its protective effect. It also
      defines the most accepted mechanism of protection on ischemichally damaged
      kidneys.

PMID- 24914486
TI  - Reaction Mechanism and Catalytic Fingerprint of Allantoin Racemase.
AB  - The stereospecific oxidative decomposition of urate into allantoin is the core of
      purine catabolism in many organisms. The spontaneous decomposition of upstream
      intermediates and the nonenzymatic racemization of allantoin lead to an
      accumulation of (R)-allantoin, because the enzymes converting allantoin into
      allantoate are specific for the (S) isomer. The enzyme allantoin racemase
      catalyzes the reversible conversion between the two allantoin enantiomers, thus
      ensuring the overall efficiency of the catabolic pathway and preventing allantoin
      accumulation. On the basis of recent crystallographic and biochemical evidence,
      allantoin racemase has been assigned to the family of cofactor-independent
      racemases, together with other amino acid racemases. A detailed computational
      investigation of allantoin racemase has been carried out to complement the
      available experimental data and to provide atomistic insight into the enzymatic
      action. Allantoin, the natural substrate of the enzyme, has been investigated at
      the quantum mechanical level, in order to rationalize its conformational and
      tautomeric equilibria, playing a key role in protein-ligand recognition and in
      the following catalytic steps. The reaction mechanism of the enzyme has been
      elucidated through quantum mechanics/molecular mechanics (QM/MM) calculations.
      The potential energy surface investigation, carried out at the QM/MM level,
      revealed a stepwise reaction mechanism. A pair of cysteine residues promotes the
      stereoinversion of a carbon atom of the ligand without the assistance of
      cofactors. Electrostatic fingerprint calculations are used to discuss the role of
      the active site residues in lowering the pKa of the substrate. The planar
      unprotonated intermediate is compared with the enolic allantoin tautomer observed
      in the active site of the crystallized enzyme. Finally, the enzymatic catalysis
      featured by allantoin racemase (AllR) is compared with that of other enzymes
      belonging to the same family.

PMID- 24914487
TI  - Reconstructive endovascular treatment of a ruptured blood blister-like aneurysm
      of anterior communicating artery.
AB  - Blood blister-like aneurysms (BBA) consist of focal wall defects covered with
      thin fibrous tissue correlated with the marked fragility of their wall; this
      concept is very important for deciding the right treatment of the latter. Until
      2008, it was thought that this type of aneurysm almost exclusively affected the
      internal carotid artery, and in particular, of its dorsal portion. Subsequently,
      it was discovered that the BBA may also be present on the anterior communicating
      artery and on the posterior cranial fossa vessels. In this article, we present a
      case of anterior communicating artery (AComA) BBA and discuss the unique
      diagnostic and therapeutic aspects of this vascular lesion. Treatment requires an
      experienced team of vascular and endovascular neurosurgeons to treat this
      hazardous group of aneurysms; endovascular stenting techniques avoid maneuvres on
      the aneurysm itself and should therefore be judged as the lowest risk and first
      choice procedures available. We found no reports in the English-language
      literature of BBA that arose from the AComA treated by a Flow-diverter stent
      (FDS) in the acute phase. BBA constitute technically challenging lesions that may
      occur at the AComA. Endovascular treatment offers a lower morbidity-mortality
      compared with surgical approaches; FDS appear to be a promising strategy.

PMID- 24914488
TI  - Quantum yield in blue-emitting anthracene derivatives: vibronic coupling density
      and transition dipole moment density.
AB  - A theoretical design principle for enhancement of the quantum yield of light
      emitting molecules is desired. For the establishment of the principle, we focused
      on the S1 states of blue-emitting anthracene derivatives: 2-methyl-9,10-di(2'
      naphthyl)anthracene (MADN), 4,9,10-bis(3',5'-diphenylphenyl)anthracene (MAM), 9
      (3',5'-diphenylphenyl)-10-(3'',5''-diphenylbiphenyl-4''-yl) anthracene (MAT), and
      9,10-bis(3''',5'''-diphenylbiphenyl-4'-yl) anthracene (TAT) [Kim et al., J.
      Mater. Chem., 2008, 18, 3376]. The vibronic coupling constants and transition
      dipole moments were calculated and analyzed by using the concepts of vibronic
      coupling density (VCD) and transition dipole moment density (TDMD), respectively.
      It is found that the driving force of the internal conversions and vibrational
      relaxations originate mainly from the anthracenylene group. On the other hand,
      fluorescence enhancement results from the large torsional distortion of the side
      groups in the S1 state. The torsional distortion is caused by the diagonal
      vibronic coupling for the lowest-frequency mode in the Franck-Condon (FC) S1
      state, which originates from a small portion of the electron density difference
      on the side groups. These findings lead to the following design principles for
      anthracene derivatives with a high quantum yield: (1) reduction in the electron
      density difference and overlap density between the S0 and S1 states in the
      anthracenylene group to suppress vibrational relaxation and radiationless
      transitions, respectively; (2) increase in the overlap density in the side group
      to enhance the fluorescence. 

PMID- 24914490
TI  - Patient experiences of autonomy and coercion while receiving legal leverage in
      forensic assertive community treatment.
AB  - Legal leverage is broadly defined as the use of legal authority to promote
      treatment adherence. It is widely utilized within mental health courts, drug
      courts, mandated outpatient treatment programs, and other intervention strategies
      for individuals with mental illness or chemical dependency who have contact with
      the criminal justice system. Nonetheless, the ethics of using legal authority to
      promote treatment adherence remains a hotly debated issue within public and
      professional circles alike. While critics characterize legal leverage as a
      coercive form of social control that undermines personal autonomy, advocates
      contend that it supports autonomy because treatment strategies using legal
      leverage are designed to promote health and independence. Despite the
      controversy, there is little evidence regarding the impact of legal leverage on
      patient autonomy as experienced and expressed by patients themselves. This report
      presents findings from a qualitative study involving six focus groups with
      severely mentally ill outpatients who received legal leverage through three
      forensic assertive community treatment (FACT) programs in Northeastern,
      Midwestern, and West Coast cities. Findings are discussed in the context of the
      self-determination theory of human motivation, and practical implications for the
      use of legal leverage are considered. 

PMID- 24914489
TI  - Booster Sessions after Cognitive-Behavioural Group Therapy for Panic Disorder:
      Impact on Resilience, Coping, and Quality of Life.
AB  - BACKGROUND: Panic disorder (PD) has a chronic nature, especially as a result of
      maladaptive coping strategies to deal with stressful events. AIMS: To evaluate
      the impact of booster sessions with cognitive techniques on coping strategies,
      resilience, and quality of life (QoL) in patients previously submitted to
      standard cognitive-behavioural group therapy (CBGT) for PD. METHOD: A controlled
      clinical trial with 44 patients with PD (intervention = 20; control = 24) who had
      previously completed a 12-week CBGT protocol. PD, anxiety, and depression
      severity symptoms were assessed at baseline and 1, 6, and 12 months after the
      booster sessions. Coping strategies, resilience, and QoL were assessed by Coping
      Strategies Inventory (CSI), Resilience Scale, and WHOQOL-BREF respectively.
      RESULTS: Over time, a significant improvement in PD and depression symptoms was
      observed in both groups. A significant increase in the QoL social relations
      domain was found in the booster group, considering a time/group interaction.
      Coping and other QoL domains did not change after the booster sessions. Changes
      in resilience were dependent on the intensity of symptoms, with negative but non
      significant correlations. CONCLUSIONS: The improvement in PD and depression
      symptoms for both groups may be a result of the group format of the intervention.
      Group booster sessions after CBGT are useful to maintain the benefits obtained
      with CBGT.

PMID- 24914491
TI  - Using financial risk measures for analyzing generalization performance of machine
      learning models.
AB  - We propose a unified machine learning model (UMLM) for two-class classification,
      regression and outlier (or novelty) detection via a robust optimization approach.
      The model embraces various machine learning models such as support vector machine
      based and minimax probability machine-based classification and regression models.
      The unified framework makes it possible to compare and contrast existing learning
      models and to explain their differences and similarities. In this paper, after
      relating existing learning models to UMLM, we show some theoretical properties
      for UMLM. Concretely, we show an interpretation of UMLM as minimizing a well
      known financial risk measure (worst-case value-at risk (VaR) or conditional VaR),
      derive generalization bounds for UMLM using such a risk measure, and prove that
      solving problems of UMLM leads to estimators with the minimized generalization
      bounds. Those theoretical properties are applicable to related existing learning
      models. 

PMID- 24914492
TI  - Severe COPD exacerbation: CT features.
AB  - Abstract Objective: To describe CT features associated with severe exacerbations
      of Chronic Obstructive Pulmonary Disease (COPD). MATERIALS AND METHODS: In this
      prospective ethical-committee-approved study, 44 COPD patients (34 men, 10 women,
      age range 49-83 years) who provided written informed consent were included at the
      time of hospital admission for severe exacerbation. Pulmonary function tests
      (PFT) and chest CT scans were performed at admission and after resolution of the
      episode following a minimum of 4 weeks free of any acute symptom. For each CT
      scan, two radiologists independently scored 15 features in each lobe and side. CT
      features and PFT results were compared for exacerbation and control through Mac
      Nemar tests and paired t-tests, respectively. RESULTS: Forced expiratory volume
      in 1 second and vital capacity improved significantly after exacerbation (p =
      0.023 and 0.012, respectively). Bronchial wall thickening and lymphadenopathy
      were graded significantly higher at exacerbation than at control by both readers
      (p ranging from < 0.001 to 0.028). Other CT features were not observed during
      exacerbation, or were so only by one reader (p ranging from < 0.001 to 0.928).
      CONCLUSION: Only lymphadenopathy and bronchial wall thickening are CT features
      associated with severe COPD exacerbation, respectively in 25% and 50% of
      patients. Our findings do not advocate a role for CT in the routine work-up of
      patients with severe COPD exacerbation.

PMID- 24914493
TI  - The high-risk patient: a challenge to be overcome.

PMID- 24914494
TI  - Identification of suitable reference genes in buffalo grass for accurate
      transcript normalization under various abiotic stress conditions.
AB  - Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR)
      is a sensitive technique for normalization of the gene expression level of target
      genes. Buffalograss (Buchloe dactyloides), a warm-season turfgrass with strong
      abiotic stress resistance, is widely used in North China. Up to now, no work was
      performed to evaluate the reference genes in buffalograss. In this study, the
      expression profiles of ten potential reference genes were examined by qRT-PCR in
      24 buffalograss samples, which were subjected to a different treatment (salt,
      osmotic, cold and heat). Three qRT-PCR analysis methods (GeNorm, NormFinder, and
      Bestkeeper) were used to evaluate the stability of gene expression. The results
      indicated that DNAJ and beta-ACTIN were the optimal reference genes for salt
      treated leaves, and the combination of PP2A and GAPDH was better reference genes
      for PEG-treated leaves. Under cold stress, DNAJ and beta-ACTIN showed less
      variety of expression level in leaves. DNAJ and GAPDH exhibited the most stable
      expression in heat-treated samples. To sum up, glyceral-dehyde-3-phosphate
      dehydrogenase (GAPDH), beta-ACTIN, DNAJ-like protein (DNAJ) and protein
      phosphatase 2A (PP2A) were selected as the most stable reference gene among all
      tested samples. To further validate the suitability of these reference genes, the
      expression levels of DREB2 (homologs of AtDREB2) were analyzed in parallel. Our
      results show that the best reference genes differed across different experimental
      conditions, and these results should enable better normalization and
      quantification of transcript levels in buffalograss in the future.

PMID- 24914495
TI  - Prenatal diagnosis of foetuses with congenital abnormalities and duplication of
      the MECP2 region.
AB  - MECP2 duplication results in a well-recognised syndrome in 100% of affected male
      children; this syndrome is characterised by severe neurodevelopmental
      disabilities and recurrent infections. However, no sonographic findings have been
      reported for affected foetuses, and prenatal molecular diagnosis has not been
      possible for this disease due to lack of prenatal clinical presentation. In this
      study, we identified a small duplication comprising the MECP2 and L1CAM genes in
      the Xq28 region in a patient from a family with severe X-linked mental
      retardation and in a prenatal foetus with brain structural abnormalities. Using
      high-resolution chromosome microarray analysis (CMA) to screen 108 foetuses with
      congenital structural abnormalities, we identified additional three foetuses with
      the MECP2 duplication. Our study indicates that ventriculomegaly, hydrocephalus,
      agenesis of the corpus callosum, choroid plexus cysts, foetal growth restriction
      and hydronephrosis might be common ultrasound findings in prenatal foetuses with
      the MECP2 duplication and provides the first set of prenatal cases with MECP2
      duplication, the ultrasonographic phenotype described in these patients will help
      to recognise the foetuses with possible MECP2 duplication and prompt the
      appropriate molecular testing. 

PMID- 24914496
TI  - Tetra-primer ARMS-PCR identifies the novel genetic variations of bovine HNF
      4alpha gene associating with growth traits.
AB  - Hepatocyte nuclear factor-4alpha (HNF-4alpha), a member of the hepatocyte nuclear
      factor family, plays an important role in regulating the expression of genes
      involved in the development, differentiation and normal function of liver and
      pancreatic beta cells, as well as the maintenance of glucose homeostasis. Tetra
      primer amplification refractory mutation system PCR (T-ARMS-PCR) is a new method
      offering fast detection and extreme simplicity at a negligible cost for SNP
      genotyping. In this paper, we characterize the polymorphisms of the bovine HNF
      4alpha gene in three Chinese indigenous cattle breeds (n=660). Six novel SNPs
      were identified including 1 mutation in the coding region and others in introns.
      The statistical analyses indicated that 4 SNPs (g.T53729C, g.A53861G, g.A65188C
      and g.T65444C) affected growth traits markedly (P<0.05) in Qinchuan cattle (2
      years after birth). Besides, haplotypes involving these 4 SNP sites in the bovine
      HNF-4alpha gene were identified and their effects on growth traits were also
      analyzed. The results showed that haplotypes 2, 7, 9 and 11 were predominant and
      accounted for 73.2%, 59.6%, and 67.1% in Qinchuan, Nanyang and Jiaxian cattle
      breeds, respectively. Hap9 (TAAT) was extremely predominant in all test
      populations, which suggested that individuals with Hap9 were more adapted to the
      environment. Furthermore, 4 combined haplotypes were constructed to guarantee the
      reliability of analysis results in Qinchuan cattle. There were also significant
      differences in body length (P<0.05). These findings will benefit for the
      application of DNA marker related to the growth traits on marker-assisted
      selection (MAS), and improve the performance of beef cattle.

PMID- 24914497
TI  - Molecular characterization of gdf9 and bmp15 genes in rare minnow Gobiocypris
      rarus and their expression upon bisphenol A exposure in adult females.
AB  - Growth differentiation factor 9 (Gdf9) and bone morphogenetic protein 15 (Bmp15)
      are members of transforming growth factor beta (TGFbeta) superfamily that plays
      important roles in regulating ovarian functions. We cloned the cDNAs of gdf9 and
      bmp15 in rare minnow Gobiocypris rarus. The full length cDNAs of gdf9 and bmp15
      were 1999 and 1721 bp, encoding 431 and 384 amino acids respectively. They both
      contained conserved TGFbeta superfamily domain, with six conserved cysteine
      residues. Tissue distribution showed that both gdf9 and bmp15 are highly
      expressed in the G. rarus ovary. Following bisphenol A (BPA) treatment, ovarian
      transcripts of gdf9 and bmp15 together with the gonadosomatic index and the
      ovarian histology were altered. It suggests that the altered gdf9 and bmp15
      expression may play roles in the weight gain and abnormal development of the
      ovary following BPA exposure.

PMID- 24914498
TI  - Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome
      sequencing.
AB  - BACKGROUND: Hoyeraal-Hreidarsson syndrome is a severe multisystem disorder that
      is characterized by bone-marrow failure, intrauterine growth retardation,
      microcephaly, immunodeficiency, and cerebellar atrophy. This rare disease shares
      clinical features with dyskeratosis congenita and, together, they are recognized
      as a group of disorders caused by telomere dysfunction. As the genetic background
      of dyskeratosis congenita or Hoyeraal-Hreidarsson syndrome has expanded rapidly,
      multiple causative genes and inheritance patterns pose a great challenge to their
      genetic diagnosis. CASE PRESENTATION: A 3-month-old boy was referred for head
      titubation and tremulous movements of the trunk. Multiple petechiae also
      developed on his face and trunk at the age of 5 months. Extensive evaluation,
      including brain magnetic resonance imaging, hematologic tests, and bone-marrow
      evaluation, revealed cerebellar atrophy and aplastic anemia. His elder brother
      exhibited a similar clinical presentation and died from sepsis after
      hematopoietic stem cell transplantation. Although skin pigmentation or nail
      dystrophy was not evident, Hoyeraal-Hreidarsson syndrome was suggested as a
      differential diagnosis. Instead of the conventional gene-specific approach with
      Sanger sequencing, we used whole-exome sequencing for the genetic diagnosis of
      this patient with possible Hoyeraal-Hreidarsson syndrome and successfully
      identified a missense mutation (c.146C>T, p.Thr49Me) in DKC1. CONCLUSION: This
      case suggests that whole-exome sequencing is particularly useful for the genetic
      diagnosis of extremely rare diseases with genetic heterogeneity, although there
      are many limitations, including cost and uneven or suboptimal coverage, to the
      application of this method as a routine genetic diagnosis.

PMID- 24914500
TI  - Melanoma early detection and awareness: how countries developing melanoma
      awareness programs could benefit from melanoma-proficient countries.
AB  - Risk factors for melanoma are well known and have guided plans for primary and
      secondary prevention. The presentation of the disease, however, varies widely
      depending on the geographic area, ethnicity, and socioeconomic status. For this
      reason, many countries have developed specific strategies to increase public
      awareness and favor early diagnosis. Awareness campaigns, doctor education, and
      screening of high-risk subjects have all contributed to improve disease outcome
      in developed countries. The role of primary care physicians is particularly
      relevant in this regard. Developing countries are trying to implement similar
      measures. Future efforts to further improve the efficacy of preventive strategies
      should focus on populations that usually escape campaigns, such as elderly men
      and people with low socioeconomic status. Fast-growing tumors also require
      specific attention.

PMID- 24914499
TI  - Protective effects of apigenin against furan-induced toxicity in mice.
AB  - Furan, a food contaminant formed by heating, is possibly carcinogenic to humans.
      In this study, we discussed the effect of administration of apigenin on furan
      induced toxicity by determining the ROS content, oxidative damage, cytokine
      levels, DNA damage, and the liver and kidney damage in a mouse model. Our data
      showed that apigenin administered at 5, 10, and 20 mg kg(-1) bw per day could
      decrease the toxicity induced by furan to different extents. On one hand,
      apigenin has the ability to increase the oxidative damage indexes of glutathione
      (GSH) and glutathione-S-transferase (GST) as well as superoxide dismutase (SOD)
      activities but decrease myeloperoxidase (MPO) activities and maleic dialdehyde
      (MDA) content in the liver and kidney of mice treated with furan. On the other
      hand, it could decrease cytokine levels of tumor necrosis factor alpha (TNF
      alpha), interleukin (IL)-1beta, and interleukin (IL)-6 but increase interleukin
      (IL)-10 in the serum of furan-treated mice. At the same time, the three
      concentrations of apigenin elected in this paper all could decrease the ROS
      content, DNA damage index of 8-hydroxy-desoxyguanosine (8-OHdG), the liver and
      kidney damage indexes of aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and lactic dehydrogenase (LDH), and blood urea nitrogen
      (BUN) and creatinine content in furan-treated mice to different extents. The
      protective effects of apigenin against furan-induced toxicity damage were mainly
      due to its excellent ability to scavenge free radicals and inhibit lipid
      oxidation. This is important when considering the use of apigenin as a dietary
      supplement for beneficial chemoprevention of furan toxicity. 

PMID- 24914502
TI  - Idiopathic Nonviral Cryoglobulinemia Treated Successfully With Rituximab.
AB  - Cryoglobulinemia is a systemic inflammatory syndrome that generally involves
      small-to-medium vessel vasculitis due to cryoglobulin-containing immune
      complexes. The therapeutic management of idiopathic cryoglobulinemic vasculitis
      has yet to be defined because no study has evaluated the best strategies.
      However, treatment of severe vasculitis is traditionally based on a combination
      of corticosteroids and immunosuppressants or plasmapheresis, and more recently
      rituximab. We report a case of 77-year-old female patient diagnosed with
      idiopathic cryoglobulinemia, treated successfully with 6 months prednisone
      tapering and 2 doses of rituximab (1 g each dose). After receiving the above
      mentioned treatment, her creatinine went back to normal with resolution of
      proteinuria and hematuria, normalization of serum complements, and significant
      improvement in her clinical picture. We conclude that rituximab could be an
      effective treatment for idiopathic cryoglobulnemia. 

PMID- 24914501
TI  - Ascorbic acid for the treatment of methemoglobinemia: the experience of a large
      tertiary care pediatric hospital.
AB  - The purpose of reporting this series of patients is to illustrate the role of
      ascorbic acid in the treatment of severe acquired methemoglobinemia (metHb),
      especially when methylene blue is not available. Medical records of affected
      patients were reviewed to collect history of exposures, food ingestion, physical
      examination, pulse oximetry, blood gas, and co-oximetry results, and outcomes.
      Five cases of acquired metHb are presented here, all of whom received treatment
      with ascorbic acid and fully recovered after 24 hours of treatment. Our series
      emphasizes that ascorbic acid is an effective alternative in the management of
      acquired metHb if methylene blue is unavailable and suggests that ascorbic acid
      infusion may be indicated in patients with glucose-6-phosphatase dehydrogenase
      deficiency. 

PMID- 24914503
TI  - Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.
AB  - Antiretroviral medications such as tenofovir have been associated with Fanconi
      syndrome (FS) usually identified within the first 1-29 months after exposure to
      the medication. We present a case of life-threatening FS which developed in a 37
      year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient
      was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later,
      and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3
      years before admission for FS. She developed nausea, vomiting, diarrhea, and
      generalized weakness over a 2-week time period and presented to the hospital. In
      the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12
      mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95
      mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap
      (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by
      antiretroviral therapy (ART) was suspected and the ART was discontinued with
      resolution of the renal abnormalities within 7 days. A non-tenofovir-containing
      ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over
      the next 8 months, the patient was without recurrence of the FS. This case report
      demonstrates the acute development of FS after prolonged exposure to tenofovir
      without exposure to additional nephrotoxins such as nonsteroidal medications or
      aminoglycosides. Tenofovir can cause FS at any time and should be considered in
      any patient presenting with renal tubular acidosis type 2 while on tenofovir
      regardless of the duration of drug exposure. 

PMID- 24914505
TI  - Can Chronic Pain Patients Be Adequately Treated Using Generic Pain Medications to
      the Exclusion of Brand-Name Ones?
AB  - According to the Food and Drug Administration (FDA) reports, approximately 8 in
      10 prescriptions filled in the United States are for generic medications, with an
      expectation that this number will increase over the next few years. The impetus
      for this emphasis on generics is the cost disparity between them and brand-name
      products. The use of FDA-approved generic drugs saved 158 billion dollars in 2010
      alone. In the current health care climate, there is continually increasing
      pressure for prescribers to write for generic alternative medications,
      occasionally at the expense of best clinical practices. This creates a conflict
      wherein both physicians and patients may find brand-name medications clinically
      superior but nevertheless choose generic ones. The issue of generic versus brand
      medications is a key component of the discussion of health payers, physicians and
      their patients. This review evaluates some of the important medications in the
      armamentarium of pain physicians that are frequently used in the management of
      chronic pain, and that are currently at the forefront of this issue, including
      Opana (oxymorphone; Endo Pharmaceuticals, Inc., Malvern, PA), Gralise
      (gabapentin; Depomed, Newark, CA), and Horizant (gabapentin enacarbil; XenoPort,
      Santa Clara, CA) that are each available in generic forms as well. We also
      discuss the use of Lyrica (pregabalin; Pfizer, New York, NY), which is currently
      unavailable as generic medication, and Cymbalta (duloxetine; Eli Lilly,
      Indianapolis, IN), which has been recently FDA approved to be available in a
      generic form. It is clear that the use of generic medications results in large
      financial savings for the cost of prescriptions on a national scale. However,
      cost-analysis is only part of the equation when treating chronic pain patients
      and undervalues the relationships of enhanced compliance due to single-daily
      dosing and stable and reliable pharmacokinetics associated with extended-duration
      preparations using either retentive technologies or delayed absorption
      strategies. Medications given to chronic pain patients should be individualized
      to best serve analgesic needs and assure patient safety primarily, based on high
      levels of scientific and economic evidence. Decisions regarding utilization
      should not be made based solely on limited or faulty assessments of cost-benefit
      analyses. 

PMID- 24914504
TI  - Prospective Clinical Trial of Rifaximin Therapy for Patients With Primary
      Sclerosing Cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver
      disease in which emerging data suggest that oral antibiotics may offer
      therapeutic effects. We enrolled patients with PSC in a 12-week, open-label pilot
      study to investigate the efficacy and safety of 550 mg of oral rifaximin twice
      daily. The primary end point was serum alkaline phosphatase (ALK) at 12 weeks.
      Secondary end points included (1) serum bilirubin, gamma-glutamyl transpeptidase,
      and Mayo PSC risk score; (2) fatigue impact scale, chronic liver disease
      questionnaire, and short form health survey (SF-36) scores; and (3) adverse
      effects (AEs). Analyses were performed with nonparametric tests. Sixteen patients
      were enrolled, among whom the median age was 40 years; 13 (81%) were male, 13 had
      inflammatory bowel disease, and baseline ALK was 342 IU/mL (interquartile range,
      275-520 IU/mL). After 12 weeks of treatment, there were no significant changes in
      ALK (median increase of 0.9% to 345 IU/mL; P = 0.47) or any of the secondary
      biochemical end points (all P > 0.05). Similarly, there were no significant
      changes in fatigue impact scale, chronic liver disease questionnaire, or SF-36
      scores (all P > 0.05). Three patients withdrew from the study due to AEs; 4
      others reported mild AEs but completed the study. In conclusion, although some
      antibiotics may have promise in treating PSC, oral rifaximin, based on the
      results herein, seems inefficacious for this indication. Future studies are
      needed to understand how the antimicrobial spectra and other properties of
      antibiotics might determine their utility in treating PSC.

PMID- 24914506
TI  - Effective Strategies in Reducing Rehospitalizations in Patients With Heart
      Failure.
AB  - Aging of the population and prolongation of the lives of patients with heart
      failure (HF) by advanced therapeutic innovations has led to an elevating number
      of patients who live with HF. The American Heart Association estimated that 5.1
      million Americans were affected with HF in 2013 and approximately 23 million
      individuals were affected worldwide. Despite the improved management approaches,
      the mortality rate is still high; less than half of the patients with HF remain
      alive after 5 years of HF diagnosis and less than a quarter of them after 10
      years. HF costs the nation a huge amount of money. The total cost comprises $34.4
      billion each year, including the health care services, medications, and loss of
      productivity. Hospitalization is a common issue in HF, estimated as primary
      diagnosis in more than 1 million each year. Readmission after initial
      hospitalization is another concern in patients with HF. Around 25% will be
      readmitted in the next 30 days after hospital discharge, out of which only one
      third is due to HF. It also costs the government an exhausting amount of money.
      The report of Medicare Payment Advisory Commission that was provided to the
      congress in 2008 showed that the expenses on HF readmissions were about $903. In
      this review, we intended to demonstrate the different strategies that could
      improve the readmission rates in patients with HF and ultimately decrease the
      health care payments. These strategies include evidence-based management
      programs, surgical therapy, risk factors adjustment, and disease monitoring. 

PMID- 24914507
TI  - Catechol-O-methyltransferase Val158Met genotype moderates the effect of
      disorganized attachment on social development in young children.
AB  - Children with histories of disorganized attachment exhibit diverse problems,
      possibly because disorganization takes at least two distinctive forms as children
      age: controlling-punitive and controlling-caregiving. This variation in the
      developmental legacy of disorganization has been attributed primarily to
      variations in children's rearing experiences. Here an alternative explanation of
      these divergent sequelae of disorganization is evaluated: one focused on
      genotype. Structural equation modeling was applied to data on 704 Norwegian
      children to test whether the catechol-O-methyltransferase Val158Met genotype
      moderates the effect of disorganized attachment, which was measured dimensionally
      at 4 years of age using the Manchester Child Attachment Story Task, on changes in
      aggressive behavior and social competence from ages 4 to 6. Children who scored
      high on disorganization and were homozygous for the valine allele displayed
      significantly greater increases in aggression and decreases in self-oriented
      social skills (e.g., self-regulation and assertiveness) over time than did their
      disorganized counterparts carrying the methionine allele, whereas disorganized
      children carrying the methionine allele increased their other-oriented social
      skill (e.g., cooperation and responsibility) scores more than did valine
      homozygous children. These results are consistent with the controlling-punitive
      and controlling-caregiving behaviors observed in disorganized children,
      suggesting that the children's genotype contributed to variations in the social
      development of disorganized children. 

PMID- 24914508
TI  - Design, synthesis and evaluation of new tricyclic endoperoxides as potential
      antiplasmodial agents.
AB  - Diastereoselective autoxidation allowed preparation of new tricyclic
      endoperoxides. These compounds and their methylated analogs were evaluated
      against the in vitro growth of Plasmodium falciparum, the malaria-causing
      parasite, showing moderate activities. However, hybrid molecules composed of the
      tricyclic peroxide moiety and 7-chloro-4-aminoquinoline were synthesized and
      displayed a marked increase in antiplasmodial activity. 

PMID- 24914509
TI  - Dysregulation of hydrogen sulphide metabolism impairs oviductal transport of
      embryos.
AB  - Embryo retention in the fallopian tube is thought to lead to ectopic pregnancy,
      which is a significant cause of morbidity. Hydrogen sulphide (H2S) is a
      gaseotransmitter produced mainly by cystathionine-gamma-lyase and cystathionine
      beta-synthase. Here we show that cystathionine-gamma-lyase and cystathionine 
      beta-synthase are ubiquitously distributed in human fallopian tube epithelium and
      that H2S signalling relaxes the spontaneous contraction of the human oviduct.
      Furthermore, an aberration in H2S signalling, either silenced or enhanced
      activity induced by pharmacologic or genetic methods, causes embryo retention and
      developmental delay in the mouse oviduct, which is partly reversed by
      administration of either GYY4137, a slow-releasing H2S donor, or NaHS. Our
      findings reveal a new regulatory mechanism for oviductal embryo transport. 

PMID- 24914510
TI  - [Prevention of stress induced ulcers: histamine-2 receptor antagonists or proton
      pump inhibitors? - gastric hemorrhage occur more often under proton pump
      inhibitors].

PMID- 24914511
TI  - [Compliance with hand hygiene guidelines on intensive care units at a university
      medical centre with surgical focus].
AB  - BACKGROUND AND AIM: Hand hygiene practice is one of the most effective measures
      to prevent healthcare-associated infections. This study examines the trends of
      hand hygiene compliance among physicians and nurses on the intensive care units
      (ICU) and hematopoetic stem cell transplantation units (HSCTU) at Hannover
      Medical School. An observational study via repeated cross-sectional assessments
      was conducted during the first 6 years of the "AKTION Saubere Hande" (ASH), i.e.
      the German adaptation of WHO's "Clean Care is Safer Care" campaign. METHODS:
      Compliance rates were directly observed in accordance with WHO definitions on the
      10 ICU and two HSCTU. Overall, 13,175 hand hygiene opportunities were observed
      between 2008 and 2013. RESULTS: In 2008, compliance rates of physicians and
      nurses did not differ significantly in statistical terms (53% vs. 57%, p=0.085).
      Physicians' compliance improved to 64% in 2011, but declined again to 48.4% in
      2013 (p < 0.001). In contrast, hand hygiene compliance among nurses had increased
      to 71.3% as soon as 2009 /10 (p < 0.001). Their compliance dropped to 55.8% in
      2013 and thus to baseline level (p=0.444), while remaining higher than that of
      physicians (p=0.003). Similar trends pertained to the surgical ICU. CONCLUSIONS:
      These results indicate that during the ASH-campaign hand hygiene compliance
      increased initially both among physicians and nurses, albeit so far not in a
      sustainable fashion. This implies an increased demand for interventions which not
      only promote motivation, but also its translation into stable and sustained
      behavior in accordance with guidelines.

PMID- 24914512
TI  - [Invasive pneumococcal disease in Germany in the era of pneumococcal conjugate
      vaccination].
AB  - BACKGROUND: Pneumococci remain a major cause of bacterial pneumonia, sepsis and
      meningitis globally. METHODS: The German National Reference Center for
      Streptococci at the Institute for Medical Microbiology of the University Hospital
      RWTH Aachen, Germany, has carried out surveillance studies on invasive
      pneumococcal disease (IPD) since 1992. This report is based on IPD-cases from
      adults and children, received between July 1992 and June 2013 and July 1997 and
      June 2013 respectively. RESULTS: From 1997-2006 the proportion of infections
      among children <= 23 months of age with serotypes included in the 7-valent
      vaccine was about 65%. Since the start of childhood vaccination in 2006 the
      percentage has continuously decreased, reaching < 5% in 2012 /2013. Also among
      adults, for whom conjugate vaccination was not indicated, this percentage
      decreased from 40-45% in 1992-2006 to about 8% in 2012 /2013. This phenomenon is
      denoted as herd protection. The resistance rate against Penicillin G remained
      under 4% among children and under 2.5% among adults over the whole study period.
      Since 2005 /2006 macrolide resistance levels have decreased to about 5% among
      children and 8% among adults. CONCLUSION: The continuous decrease of vaccine
      serotypes as well as the decreasing IPD incidence since the beginning of
      childhood vaccination document the success of pneumococcal conjugate vaccination.

PMID- 24914513
TI  - [83-year old abdominal mass after coronary stent implantation].

PMID- 24914514
TI  - [Gastrointestinal infections].

PMID- 24914515
TI  - [Azole resistance in Aspergillus fumigatus - epidemiology and detection in
      immunocompromised patients in Germany].

PMID- 24914516
TI  - [Surveillance reports on pathogens and their antibiotic resistance patterns - a
      recommendation for standardization].
AB  - Surveillance reports on infectious agents and their antibiotic resistance
      patterns as well as on the usage of antibiotics are now enforced by law for many
      medical institutions in Germany. However, specific practice-oriented
      recommendations concerning the appropriate extent and informative mode of
      presentation are lacking. This consensus statement resulted from the experience
      from five German university hospitals in handling data from infection
      epidemiology and in the various possibilities for the presentation of
      surveillance reports. The consensus statement provides recommendations for the
      preparation of the legally demanded surveillance reports, extending the existing
      regulations. The relevance of statements on frequency and quality of
      microbiological tests is included. Furthermore, modes for the standardization of
      the data analysis are suggested in order to achieve a regional and national
      comparability of the results on a high quality level, similarly to the
      established standardized surveillance of nosocomial infections. This consensus
      statement describes the form in which the legally enforced reports can be
      presented in an informative and standardized way in order to facilitate the
      deduction and realization of preventive measurements. 

PMID- 24914517
TI  - Control of sample alignment mode for hybrid lamellar systems based on gold
      nanoparticles.
AB  - New hybrid materials made of gold nanoparticles functionalized by mesogenic
      ligands form laminated smectic phases. Mechanical shearing produces macro size
      domains with uniformly oriented layers with the layer normal either perpendicular
      (perpendicular mode) or parallel (transverse mode) to the shearing direction.
      This is in contrast to low weight and polymer liquid crystals which usually show
      parallel mode of orientation. 

PMID- 24914518
TI  - Influence of weather, rank, and home advantage on football outcomes in the Gulf
      region.
AB  - PURPOSE: The objective of this study was to investigate the effects of weather,
      rank, and home advantage on international football match results and scores in
      the Gulf Cooperation Council (GCC) region. METHODS: Football matches (n = 2008)
      in six GCC countries were analyzed. To determine the weather influence on the
      likelihood of favorable outcome and goal difference, generalized linear model
      with a logit link function and multiple regression analysis were performed.
      RESULTS: In the GCC region, home teams tend to have greater likelihood of a
      favorable outcome (P < 0.001) and higher goal difference (P < 0.001). Temperature
      difference was identified as a significant explanatory variable when used
      independently (P < 0.001) or after adjustment for home advantage and team ranking
      (P < 0.001). The likelihood of favorable outcome for GCC teams increases by 3%
      for every 1-unit increase in temperature difference. After inclusion of
      interaction with opposition, this advantage remains significant only when playing
      against non-GCC opponents. While home advantage increased the odds of favorable
      outcome (P < 0.001) and goal difference (P < 0.001) after inclusion of
      interaction term, the likelihood of favorable outcome for a GCC team decreased (P
      < 0.001) when playing against a stronger opponent. Finally, the temperature and
      wet bulb globe temperature approximation were found as better indicators of the
      effect of environmental conditions than absolute and relative humidity or heat
      index on match outcomes. CONCLUSIONS: In GCC region, higher temperature increased
      the likelihood of a favorable outcome when playing against non-GCC teams.
      However, international ranking should be considered because an opponent with a
      higher rank reduced, but did not eliminate, the likelihood of a favorable
      outcome.

PMID- 24914520
TI  - Myocardial crypt in an asymptomatic young athlete: how to interpret?
AB  - Myocardial crypts are extensions of blood signal penetrating the compact
      myocardium and are considered in literature as either a distinctive cardiac
      magnetic resonance (CMR) imaging marker for hypertrophic cardiomyopathy or as
      benign congenital malformations. What if CMR reveals a myocardial crypt in the
      presence of an altered ECG in an asymptomatic, enlarged young athlete's heart?
      The illustrated case demonstrates that new insights in CMR can also require
      further diagnostic interventions, which might have deleterious consequences for
      the individual athlete because of the uncertain interpretation of some findings
      in the demanding new world of a rapidly developing diagnostic imaging technique. 

PMID- 24914519
TI  - Association between physical activity and depressive symptoms: midlife women in
      SWAN.
AB  - INTRODUCTION: The relation of physical activity (PA) and positive mood has been
      the focus of considerable research, which were primarily cross-sectional. This
      study was done to evaluate the relation between PA and high depressive symptoms
      across time and to examine whether being physically active attenuates the risk of
      depressive symptoms in midlife women. METHODS: The present study is a
      longitudinal observational study on the menopausal transition in a multiethnic
      population. Ten years of data on 2891 women were analyzed. The participants were
      women from seven geographic areas nationwide, age 42-52 yr at baseline, still
      menstruating, and not using exogenous reproductive hormones. PA was measured with
      the Kaiser Permanente Physical Activity Scale. The main outcome measure,
      depressive symptoms, was assessed with the Center for Epidemiological Studies
      Depression Scale (CES-D), with primary outcome of CES-D score of 16 or higher.
      RESULTS: In mixed effect logistic regression models adjusted for covariates,
      compared with inactivity, PA meeting PA guidelines (approximating public health
      guidelines) and PA below PA guidelines were each associated with lower risk of
      high depressive symptoms (CES-D score of 16 or higher) (odds ratio, 0.52; 95%
      confidence interval, 0.40-0.70; and odds ratio, 0.81; 95% confidence interval,
      0.67-0.98, respectively] across 10 yr. Being married, Japanese and Hispanic
      ethnicity, current smoking, reporting very upsetting life events, using
      antidepressive medications, having hot flashes, and high body mass index were all
      positively associated with high depressive symptoms, whereas high social support
      was negatively associated. CONCLUSIONS: Higher PA was associated with lower
      levels of depressive symptoms persistently over 10 yr, independent of potential
      confounders. Our findings suggest that reaching moderate-intensity PA levels
      during midlife may be protective against depressive symptoms.

PMID- 24914522
TI  - Non-parametric Bayesian graph models reveal community structure in resting state
      fMRI.
AB  - Modeling of resting state functional magnetic resonance imaging (rs-fMRI) data
      using network models is of increasing interest. It is often desirable to group
      nodes into clusters to interpret the communication patterns between nodes. In
      this study we consider three different nonparametric Bayesian models for node
      clustering in complex networks. In particular, we test their ability to predict
      unseen data and their ability to reproduce clustering across datasets. The three
      generative models considered are the Infinite Relational Model (IRM), Bayesian
      Community Detection (BCD), and the Infinite Diagonal Model (IDM). The models
      define probabilities of generating links within and between clusters and the
      difference between the models lies in the restrictions they impose upon the
      between-cluster link probabilities. IRM is the most flexible model with no
      restrictions on the probabilities of links between clusters. BCD restricts the
      between-cluster link probabilities to be strictly lower than within-cluster link
      probabilities to conform to the community structure typically seen in social
      networks. IDM only models a single between-cluster link probability, which can be
      interpreted as a background noise probability. These probabilistic models are
      compared against three other approaches for node clustering, namely Infomap,
      Louvain modularity, and hierarchical clustering. Using 3 different datasets
      comprising healthy volunteers' rs-fMRI we found that the BCD model was in general
      the most predictive and reproducible model. This suggests that rs-fMRI data
      exhibits community structure and furthermore points to the significance of
      modeling heterogeneous between-cluster link probabilities. 

PMID- 24914524
TI  - Transport of carbon colloid supported nanoscale zero-valent iron in saturated
      porous media.
AB  - Injection of nanoscale zero-valent iron (nZVI) has recently gained great interest
      as emerging technology for in-situ remediation of chlorinated organic compounds
      from groundwater systems. Zero-valent iron (ZVI) is able to reduce organic
      compounds and to render it to less harmful substances. The use of nanoscale
      particles instead of granular or microscale particles can increase dechlorination
      rates by orders of magnitude due to its high surface area. However, classical
      nZVI appears to be hampered in its environmental application by its limited
      mobility. One approach is colloid supported transport of nZVI, where the nZVI
      gets transported by a mobile colloid. In this study transport properties of
      activated carbon colloid supported nZVI (c-nZVI; d50=2.4MUm) are investigated in
      column tests using columns of 40cm length, which were filled with porous media. A
      suspension was pumped through the column under different physicochemical
      conditions (addition of a polyanionic stabilizer and changes in pH and ionic
      strength). Highest observed breakthrough was 62% of the injected concentration in
      glass beads with addition of stabilizer. Addition of mono- and bivalent salt,
      e.g. more than 0.5mM/L CaCl2, can decrease mobility and changes in pH to values
      below six can inhibit mobility at all. Measurements of colloid sizes and zeta
      potentials show changes in the mean particle size by a factor of ten and an
      increase of zeta potential from -62mV to -80mV during the transport experiment.
      However, results suggest potential applicability of c-nZVI under field
      conditions. 

PMID- 24914523
TI  - Assessing contaminant-removal conditions and plume persistence through analysis
      of data from long-term pump-and-treat operations.
AB  - Historical groundwater-withdrawal and contaminant-concentration data collected
      from long-term pump-and-treat operations were analyzed and used to examine
      contaminant mass discharge (CMD) and mass-removal behavior for multiple sites.
      Differences in behavior were observed, and these differences were consistent with
      the nature of contaminant distributions and subsurface properties of the sites.
      For example, while CMD exhibited a relatively rapid decline during the initial
      stage of operation for all three sites, the rate of decline varied. The greatest
      rate was observed for the PGN site, whereas the lowest rate was observed for the
      MOT site. In addition, the MOT site exhibited the lowest relative reduction in
      CMD. These results are consistent with the actuality that the MOT site likely
      contains the greatest proportion of poorly accessible contaminant mass, given
      that it comprises a combined alluvium and fractured-bedrock system in which
      solvent and dissolved mass are present directly in the bedrock. The relative
      contributions of the source zones versus the plumes to total CMD were determined.
      Constrained contaminant mass removal was observed to influence the plumes for all
      three sites, and was attributed to a combination of uncontrolled (or imperfectly
      controlled) sources, back diffusion, and well-field hydraulics. The results
      presented herein illustrate that detailed analysis of operational pump-and-treat
      data can be a cost-effective method for providing value-added characterization of
      contaminated sites. 

PMID- 24914525
TI  - Dissolved organic carbon ameliorates the effects of UV radiation on a freshwater
      fish.
AB  - Anthropogenic activities over the past several decades have depleted
      stratospheric ozone, resulting in a global increase in ultraviolet radiation
      (UVR). Much of the negative effects of UVR in aquatic systems is minimized by
      dissolved organic carbon (DOC) which is known to attenuate UVR across the water
      column. The skin of many fishes contains large epidermal club cells (ECCs) that
      are known to play a role in innate immune responses and also release chemical
      alarm cues that warn other fishes of danger. This study investigated the effects
      of in vivo UVR exposure to fathead minnows (Pimephales promelas), under the
      influence of two sources of DOC: Sigma Aldrich humic acid, a coal based
      commercial source of DOC and Luther Marsh natural organic matter, a terrigenous
      source of DOC. Specifically, we examined ECC investment and physiological stress
      responses and found that fish exposed to high UVR, in the presence of either
      source of DOC, had higher ECC investment than fish exposed to high UVR only.
      Similarly, exposure to high UVR under either source of DOC, reduced cortisol
      levels relative to that in the high UVR only treatment. This indicates that DOC
      protects fish from physiological stress associated with UVR exposure and helps
      maintain production of ECC under conditions of UVR exposure. 

PMID- 24914526
TI  - First evaluation of illicit and licit drug consumption based on wastewater
      analysis in Fort de France urban area (Martinique, Caribbean), a transit area for
      drug smuggling.
AB  - Drugs of abuse are increasingly consumed worldwide. Such consumption could be
      back-calculated based on wastewater content. The West Indies, with its coca
      production and its thriving illicit drug market, is both a hub of world cocaine
      trafficking and a place where its consumption is prevalent particularly in the
      form of crack. The present study will firstly investigate Caribbean consumption
      by a daily 5 to 7 day sampling campaign of composite wastewater samples from the
      four wastewater treatment plants of the Martinique capital, including working and
      non-working periods. The local consumption of cocaine is ten to thirty times
      higher than OECD standards because of the prevalence of crack. The excretion
      coefficient for crack consumption and the impact of temperature on drug stability
      need further investigation. However, the low diversity of illicit drugs consumed
      and the crack prevalence suggest practices driven by the transiting of drugs for
      international trafficking.

PMID- 24914527
TI  - Distribution coefficients (Kd) of strontium and significance of oxides and
      organic matter in controlling its partitioning in coastal regions of Japan.
AB  - The Fukushima Daiichi Nuclear Power Plant accident in March 2011 resulted in the
      release of large quantities of a long-lived radioactive strontium (i.e. (90)Sr;
      half-life: 28.8 y) into the coastal areas of Japan. (90)Sr release was dispersed
      and mixed into the water column, and will eventually be deposited into sediment.
      Because factors controlling seawater-sediment partitioning in the coastal marine
      environments are not fully understood, we developed seawater-sediment
      distribution coefficients, Kd (L/kg), for Sr in coastal regions of Japan by means
      of sediment-water partitioning experiments. (85)Sr was used as a radiotracer and
      conditions were designed to mimic the environmental systems of the sampling sites
      as closely as possible. Experimentally determined Kd values (Kd-ex) varied
      between 0.3 and 3.3 L/kg (mean, 1.4 L/kg), and the variation in Kd-ex was
      attributed to the percentage of Sr in the exchangeable fraction in the sediment.
      Kd-ex values were used, along with the measured concentrations of (88)Sr, a
      stable naturally occurring Sr isotope in seawater and sediment, to estimate the
      concentrations of exchangeable Sr in the sediment. Estimates ranged from 2.1 to
      24.3 MUg/kg, or 1.3-15.7% of the total (88)Sr concentration in the sediment.
      Significant correlations existed between the estimated concentrations of
      exchangeable Sr, and the organic matter and the oxide/hydrous oxide contents.
      When organic contents were greater than 0.38%, Sr binds to organic surface sites
      more strongly than to the other sites. Results indicate that binding of Sr to the
      surface of sedimentary particles was influenced by grain size, iron and manganese
      oxides, and organic matter. Furthermore, the information presented here could be
      useful to estimate Kd values for anthropogenic (90)Sr in sediment in the coastal
      marine environment.

PMID- 24914528
TI  - Occurrence and human health risk of wastewater-derived pharmaceuticals in a
      drinking water source for Shanghai, East China.
AB  - Pharmaceuticals are heavily used to improve human and animal health, resulting in
      the frequent contamination of aquatic environments with pharmaceutical residues,
      which has raised considerable concern in recent years. When inadequately removed
      from drinking water in water treatment plants, pharmaceuticals can have potential
      toxic effects on human health. This study investigated the spatial distributions
      and seasonal variations of five pharmaceuticals, including ibuprofen (IBP),
      ketoprofen (KEP), naproxen (NPX), diclofenac (DFC), and clofibric acid (CA), in
      the Huangpu River system (a drinking water source for Shanghai) over a period of
      almost two years as well as the associated risk to human health for different age
      groups. All of the targets were ubiquitous in the river water, with levels
      decreasing in the following order: KEP (mean: 28.6 ng/L)~IBP (23.3 ng/L)>DFC
      (13.6 ng/L)~NPX (12.3 ng/L)>CA (1.6ng/L). The concentrations of all of the
      investigated compounds were at the low or medium end of the global range. The
      upstream tributaries contained lower IBP but higher NPX than did the mainstream
      and downstream tributaries. However, no significant variations were found in the
      levels of KEP, DFC, or CA at the different sampling sites. Except for CA in the
      mainstream, significantly higher pharmaceutical levels were observed in the dry
      season than in the wet season. Overall, a very low risk of the selected
      pharmaceuticals for human health via drinking water was observed, but future
      studies are needed to examine the fate and chronic effects of all pharmaceuticals
      in aquatic environments. To our knowledge, this is the first report to
      investigate the human health risk of pharmaceuticals in raw drinking water in
      China.

PMID- 24914529
TI  - Assessing effects of the fungicide tebuconazole to heterotrophic microbes in
      aquatic microcosms.
AB  - Aquatic ecological risk assessment of fungicides in Europe under Regulation
      1107/2009/EC does not currently assess risk to non-target bacteria and fungi.
      Rather, regulatory acceptable concentrations based on ecotoxicological data
      obtained from studies with fish, invertebrates and primary producers (including
      algae) are assumed to be protective to all other aquatic organisms. Here we
      explore the validity of this assumption by investigating the effects of a
      fungicide (tebuconazole) applied at its "non-microbial" HC5 concentration (the
      concentration that is hazardous to 5% of the tested taxa) and derived from acute
      single species toxicity tests on fish, invertebrates and primary producers
      (including algae) on the community structure and functioning of heterotrophic
      microbes (bacteria and aquatic fungi) in a semi-field study, using novel
      molecular techniques. In our study, a treatment-related effect of tebuconazole
      (238 MUg/L) on either fungal biomass associated with leaf material or leaf
      decomposition or the composition of the fungal community associated with sediment
      could not be demonstrated. Moreover, treatment-related effects on bacterial
      communities associated with sediment and leaf material were not detected.
      However, tebuconazole exposure did significantly reduce conidia production and
      altered fungal community composition associated with leaf material. An effect on
      a higher trophic level was observed when Gammarus pulex were fed tebuconazole
      exposed leaves, which caused a significant decrease in their feeding rate.
      Therefore, tebuconazole may affect aquatic fungi and fungally mediated processes
      even when applied at its "non-microbial" HC5 concentration.

PMID- 24914530
TI  - Socioeconomic influences on biodiversity, ecosystem services and human well
      being: a quantitative application of the DPSIR model in Jiangsu, China.
AB  - One focus of ecosystem service research is the connection between biodiversity,
      ecosystem services and human well-being as well as the socioeconomic influences
      on them. Despite existing investigations, exact impacts from the human system on
      the dynamics of biodiversity, ecosystem services and human well-being are still
      uncertain because of the insufficiency of the respective quantitative analyses.
      Our research aims are discerning the socioeconomic influences on biodiversity,
      ecosystem services and human well-being and demonstrating mutual impacts between
      these items. We propose a DPSIR framework coupling ecological integrity,
      ecosystem services as well as human well-being and suggest DPSIR indicators for
      the case study area Jiangsu, China. Based on available statistical and surveying
      data, we revealed the factors significantly impacting biodiversity, ecosystem
      services and human well-being in the research area through factor analysis and
      correlation analysis, using the 13 prefecture-level cities of Jiangsu as samples.
      The results show that urbanization and industrialization in the urban areas have
      predominant positive influences on regional biodiversity, agricultural
      productivity and tourism services as well as rural residents' living standards.
      Additionally, the knowledge, technology and finance inputs for agriculture also
      have generally positive impacts on these system components. Concerning regional
      carbon storage, non-cropland vegetation cover obviously plays a significant
      positive role. Contrarily, the expansion of farming land and the increase of
      total food production are two important negative influential factors of
      biodiversity, ecosystem's food provisioning service capacity, regional tourism
      income and the well-being of the rural population. Our study provides a promising
      approach based on the DPSIR model to quantitatively capture the socioeconomic
      influential factors of biodiversity, ecosystem services and human well-being for
      human-environmental systems at regional scales. 

PMID- 24914531
TI  - The relationship between anammox and denitrification in the sediment of an inland
      river.
AB  - This study measured the microbial processes of anaerobic ammonium oxidation
      (anammox) and denitrification in sediment sampled from two sites in the estuary
      of an inland river (Koisegawa River, Ibaragi prefecture, Japan) using a nitrogen
      isotope pairing technique (IPT). The responses of anammox and denitrification
      activities to temperature and nitrate concentration were also evaluated. Further,
      to elucidate the correlation between anammox and denitrification processes, an
      inhibition experiment was conducted, using chlorate to inhibit the first step of
      denitrification. Denitrification activity was much higher than anammox activity,
      and it reached a maximum at the surface layer in February 2012. Denitrification
      activity decreased as sediment depth increased, and a similar phenomenon was
      observed for anammox activity in the sediment of site A, where aquatic plants
      were absent from the surroundings. The activities of both denitrification and
      anammox were temperature-dependent, but they responded differently to changes in
      incubation temperature. Compared to a linear increase in denitrification as
      temperature rose to 35  degrees C, the optimal temperature for anammox was 25 
      degrees C, after which the activity decreased sharply. At the same time, both
      anammox and denitrification activities increased with NO3(-) concentration. The
      Michaelis-Menten kinetic constants (Vmax and Km) of denitrification were
      significantly higher than those of the anammox process. Furthermore, anammox
      activity decreased accordingly when the first step of denitrification was
      inhibited, which probably reduced the amount of the intermediate NO2(-). Our
      study provides the first direct exploration of the denitrification-dependent
      correlation of anammox activity in the sediment of inland river.

PMID- 24914532
TI  - Effect of home food processing on chlordecone (organochlorine) content in
      vegetables.
AB  - Decades after their use and their ban, organochlorine pesticides still pollute
      soil, water and food and lead to human and ecosystem exposure. In the case of
      chlordecone, human exposure is mainly due to the consumption of polluted food. We
      studied the effect of preparation and cooking in five vegetable products, three
      root vegetables (yam, dasheen and sweet potato) and two cucurbits (cucumber and
      pumpkin), among the main contributors to exposure to chlordecone in food in the
      French West Indies. Boiling the vegetables in water had no effect on chlordecone
      content of the vegetables and consequently on consumer exposure. The peel was
      three to 40-fold more contaminated than the pulp except cucumber, where the
      difference was less contrasted. The edible part is thus significantly less
      contaminated and peeling is recommended after rinsing to reduce consumer
      exposure, particularly for food grown in home gardens with contaminated soils.
      The type of soil had no consistent effect on CLD distribution but plot did. Peel
      and pulp composition (lipids and fibers) appear to partially account for CLD
      distribution in the product. 

PMID- 24914534
TI  - Residues of chromium, nickel, cadmium and lead in Rook Corvus frugilegus
      eggshells from urban and rural areas of Poland.
AB  - We examined the concentrations of chromium (Cr), nickel (Ni), cadmium (Cd) and
      lead (Pb) in Rook Corvus frugilegus eggshells from 43 rookeries situated in rural
      and urban areas of western (=intensive agriculture) and eastern (=extensive
      agriculture) Poland. We found small ranges in the overall level of Cr (the
      difference between the extreme values was 1.8-fold; range of concentrations=5.21
      9.40 Cr ppm), Ni (3.5-fold; 1.15-4.07 Ni ppm), and Cd (2.6-fold; 0.34-0.91 Cd
      ppm), whereas concentrations of Pb varied markedly, i.e. 6.7-fold between extreme
      values (1.71-11.53 Pb ppm). Eggshell levels of these four elements did not differ
      between rural rookeries from western and eastern Poland, but eggshells from
      rookeries in large/industrial cities had significantly higher concentrations of
      Cr, Ni and Pb than those from small towns and villages. Our study suggests that
      female Rooks exhibited an apparent variation in the intensity of trace metal
      bioaccumulation in their eggshells, that rapid site-dependent bioaccumulation of
      Cu, Cr, Ni and Pb occurs as a result of the pollution gradient (rural<urban), and
      that Cd levels are probably regulated physiologically, even though these were
      relatively high, which could be treated as an overall proxy of a heavy Cd load in
      the soil environment.

PMID- 24914533
TI  - Associations between land cover categories, soil concentrations of arsenic, lead
      and barium, and population race/ethnicity and socioeconomic status.
AB  - The potential of using land cover/use categories as a proxy for soil metal
      concentrations was examined by measuring associations between Anderson land cover
      category percentages and soil concentrations of As, Pb, and Ba in ten sampling
      areas. Land cover category and metal associations with ethnicity and
      socioeconomic status at the United States Census 2000 block and block group
      levels also were investigated. Arsenic and Pb were highest in urban locations; Ba
      was a function of geology. Consistent associations were observed between
      urban/built up land cover, and Pb and poverty. Land cover can be used as proxy
      for metal concentrations, although associations are metal-dependent. 

PMID- 24914535
TI  - Differential methylation of TCF7L2 promoter in peripheral blood DNA in newly
      diagnosed, drug-naive patients with type 2 diabetes.
AB  - TCF7L2 is the susceptibility gene for Type 2 diabetes (T2D) with the largest
      effect on disease risk that has been discovered to date. However, the mechanisms
      by which TCF7L2 contributes to the disease remain largely elusive. In addition,
      epigenetic mechanisms, such as changes in DNA methylation patterns, might have a
      role in the pathophysiology of T2D. This study aimed to investigate the
      differences in terms of DNA methylation profile of TCF7L2 promoter gene between
      type 2 diabetic patients and age- and Body Mass Index (BMI)- matched controls. We
      included 93 type 2 diabetic patients that were recently diagnosed for T2D and
      exclusively on diet (without any pharmacological treatment). DNA was extracted
      from whole blood and DNA methylation was assessed using the Sequenom EpiTYPER
      system. Type 2 diabetic patients were more insulin resistant than their matched
      controls (mean HOMA IR 2.6 vs 1.8 in controls, P<0.001) and had a poorer beta
      cell function (mean HOMA B 75.7 vs. 113.6 in controls, P<0.001). Results showed
      that 59% of the CpGs analyzed in TCF7L2 promoter had significant differences
      between type 2 diabetic patients and matched controls. In addition, fasting
      glucose, HOMA-B, HOMA-IR, total cholesterol and LDL-cholesterol correlated with
      methylation in specific CpG sites of TCF7L2 promoter. After adjustment by age,
      BMI, gender, physical inactivity, waist circumference, smoking status and
      diabetes status uniquely fasting glucose, total cholesterol and LDL-cholesterol
      remained significant. Taken together, newly diagnosed, drug-naive type 2 diabetic
      patients display specific epigenetic changes at the TCF7L2 promoter as compared
      to age- and BMI-matched controls. Methylation in TCF7L2 promoter is further
      correlated with fasting glucose in peripheral blood DNA, which sheds new light on
      the role of epigenetic regulation of TCF7L2 in T2D. 

PMID- 24914536
TI  - Intent to participate in future cervical cancer screenings is lower when
      satisfaction with the decision to be vaccinated is neutral.
AB  - BACKGROUND: HPV vaccination programs have adversely affected participation in
      future cervical cancer screening. The purpose of this study is to determine the
      influence of decision satisfaction with accepting/rejecting the HPV vaccine, as
      well as traditional clinical factors, on the intent to participate in future
      screening. METHODS AND FINDINGS: From January 2011 through August 2012 women 18
      26 years old presenting for health care in an urban college student health and
      wellness clinic in the US Midwest were asked to complete a descriptive and
      medical history survey including a six element decisional satisfaction survey
      scored on 5-point Likert scales, where the intent to participate in future
      cervical cancer screening was measured. Of the 568 women who completed the
      decisional satisfaction survey, 17% of those <21 years and 7% >= 21 years
      indicated no intent to participate in future cervical cancer screenings. Among
      women of current screening age, the univariate risk factors of race/ethnicity,
      contraceptive use, number of lifetime sexual partners, and receipt of HPV vaccine
      were not predictors of intent for future cervical cancer screening. Instead, only
      a history of a prior Pap test was a significant positive predictor and only a
      decisional satisfaction of 'neutral' (Likert score = 3) for any of the four
      decisional satisfaction elements was a significant negative predictor. For the
      decisional satisfaction element "best for me personally", there was a 78%
      decreased likelihood of intending to participate in future screening if the
      satisfaction was neutral rather than firm (aOR = 0.22, 95% CI: 0.05-0.91) and a
      26 fold increased likelihood if she had had a prior Pap test (aOR = 26, 95% CI: 5
      133). CONCLUSIONS: HPV vaccination implementation programs must help women be the
      owner of their decision around HPV vaccination and understand the importance of
      future participation in cervical cancer screening.

PMID- 24914537
TI  - Artificial neural network accurately predicts hepatitis B surface antigen
      seroclearance.
AB  - BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) seroclearance and
      seroconversion are regarded as favorable outcomes of chronic hepatitis B (CHB).
      This study aimed to develop artificial neural networks (ANNs) that could
      accurately predict HBsAg seroclearance or seroconversion on the basis of
      available serum variables. METHODS: Data from 203 untreated, HBeAg-negative CHB
      patients with spontaneous HBsAg seroclearance (63 with HBsAg seroconversion), and
      203 age- and sex-matched HBeAg-negative controls were analyzed. ANNs and logistic
      regression models (LRMs) were built and tested according to HBsAg seroclearance
      and seroconversion. Predictive accuracy was assessed with area under the receiver
      operating characteristic curve (AUROC). RESULTS: Serum quantitative HBsAg
      (qHBsAg) and HBV DNA levels, qHBsAg and HBV DNA reduction were related to HBsAg
      seroclearance (P<0.001) and were used for ANN/LRM-HBsAg seroclearance building,
      whereas, qHBsAg reduction was not associated with ANN-HBsAg seroconversion (P =
      0.197) and LRM-HBsAg seroconversion was solely based on qHBsAg (P = 0.01). For
      HBsAg seroclearance, AUROCs of ANN were 0.96, 0.93 and 0.95 for the training,
      testing and genotype B subgroups respectively. They were significantly higher
      than those of LRM, qHBsAg and HBV DNA (all P<0.05). Although the performance of
      ANN-HBsAg seroconversion (AUROC 0.757) was inferior to that for HBsAg
      seroclearance, it tended to be better than those of LRM, qHBsAg and HBV DNA.
      CONCLUSIONS: ANN identifies spontaneous HBsAg seroclearance in HBeAg-negative CHB
      patients with better accuracy, on the basis of easily available serum data. More
      useful predictors for HBsAg seroconversion are still needed to be explored in the
      future.

PMID- 24914538
TI  - Dengue serosurvey in Sint Eustatius.
AB  - Four distinct serotypes of dengue viruses (DENV) are the cause of re-emerging
      dengue fever (DF) and dengue hemorrhagic fever (DHF). Dengue circulation in the
      Caribbean has gone from none or single serotype to multiple serotypes co
      circulating with reports of continuing cycles of progressively more severe
      disease in the region. Few studies have investigated dengue on Sint Eustatius.
      Blood samples were collected to determine the prevalence of antibodies against
      dengue in the Sint Eustatius population. Greater than 90% of the serum samples
      (184 of 204) were positive for anti-flavivirus antibodies by enzyme linked
      immunosorbance assay (ELISA). Plaque reduction neutralization test (PRNT),
      specific for dengue viruses, showed that 171 of these 184 flavivirus antibody
      positive sera had a neutralization titer against one or more DENV serotypes. A
      majority of the sera (62%) had neutralizing antibody to all four dengue
      serotypes. Only 26 PRNT positive sera (15%) had monotypic dengue virus
      neutralizing antibody, most of which (20 of 26) were against DENV2. Evidence of
      infection with all four serotypes was observed across all age groups except in
      the youngest age group (10-19 years) which contained only DENV2 positive
      individuals. In a multiple logistic regression model, only the length of
      residence on the island was a predictor of a positive dengue PRNT50 result. To
      our knowledge this is the first dengue serosurveillance study conducted on Sint
      Eustatius since the 1970s. The lack of antibodies to the DEN1, 3, and 4 in the
      samples collected from participants under 20 years of age suggests that only DEN2
      has circulated on island since the early 1990s. The high prevalence of antibodies
      against dengue (83.8%) and the observation that the length of time on the island
      was the strongest predictor of infection suggests dengue is endemic on Sint
      Eustatius and a public health concern that warrants further investigation. 

PMID- 24914540
TI  - Effects of fertilization and clipping on carbon, nitrogen storage, and soil
      microbial activity in a natural grassland in southern China.
AB  - Grassland managements can affect carbon (C) and nitrogen (N) storage in grassland
      ecosystems with consequent feedbacks to climate change. We investigated the
      impacts of compound fertilization and clipping on grass biomass, plant and soil
      (0-20 cm depth) C, N storage, plant and soil C: N ratios, soil microbial activity
      and diversity, and C, N sequestration rates in grassland in situ in the National
      Dalaoling Forest Park of China beginning July, 2011. In July, 2012, the
      fertilization increased total biomass by 30.1%, plant C by 34.5%, plant N by
      79.8%, soil C by 18.8% and soil N by 23.8% compared with the control,
      respectively. Whereas the clipping decreased total biomass, plant C and N, soil C
      and N by 24.9%, 30.3%, 39.3%, 18.5%, and 19.4%, respectively, when compared to
      the control. The plant C: N ratio was lower for the fertilization than for the
      control and the clipping treatments. The soil microbial activity and diversity
      indices were higher for the fertilization than for the control. The clipping
      generally exhibited a lower level of soil microbial activity and diversity
      compared to the control. The principal component analysis indicated that the soil
      microbial communities of the control, fertilization and clipping treatments
      formed three distinct groups. The plant C and N sequestration rates of the
      fertilization were significantly higher than the clipping treatment. Our results
      suggest that fertilization is an efficient management practice in improving the C
      and N storage of the grassland ecosystem via increasing the grass biomass and
      soil microbial activity and diversity. 

PMID- 24914541
TI  - The combined toxic and genotoxic effects of Cd and As to plant bioindicator
      Trifolium repens L.
AB  - This study was undertaken to investigate combined toxic and genotoxic effects of
      cadmium (Cd) and arsenic (As) on white clover, a pollutant sensitive plant
      frequently used as environmental bioindicator. Plants were exposed to soil spiked
      with increasing concentrations of cadmium sulfate (20, 40 and 60 mg Kg-1) or
      sodium arsenite (5, 10 and 20 mg Kg-1) as well as with their combinations.
      Metal(loid) bioavailability was assessed after soil contamination, whereas plant
      growth, metal(loid) concentration in plant organs and DNA damage were measured at
      the end of plant exposition. Results showed that individual and joint toxicity
      and genotoxicity were related to the concentration of Cd and As measured in plant
      organs, and that As concentration was the most relevant variable. Joint effects
      on plant growth were additive or synergistic, whereas joint genotoxic effects
      were additive or antagonistic. The interaction between Cd and As occurred at both
      soil and plant level. In soil the presence of As limited the bioavailability of
      Cd, whereas the presence of Cd increased the bioavailability of As. Nevertheless
      only As biovailability determined the amount of As absorbed by plants. The amount
      of Cd absorbed by plant was not linearly correlated with the fraction of
      bioavailable Cd in soil suggesting the involvement of additional factors, such as
      plant uptake mechanisms. These results reveal that the simultaneous presence in
      soil of Cd and As, although producing an additive or synergistic toxic effect on
      Trifolium repens L. growth, generates a lower DNA damage. 

PMID- 24914542
TI  - New horizons for plant translational research.

PMID- 24914539
TI  - Rho GTPases, phosphoinositides, and actin: a tripartite framework for efficient
      vesicular trafficking.
AB  - Rho GTPases are well known regulators of the actin cytoskeleton that act by
      binding and activating actin nucleators. They are therefore involved in many
      actin-based processes, including cell migration, cell polarity, and membrane
      trafficking. With the identification of phosphoinositide kinases and phosphatases
      as potential binding partners or effectors, Rho GTPases also appear to
      participate in the regulation of phosphoinositide metabolism. Since both actin
      dynamics and phosphoinositide turnover affect the efficiency and the fidelity of
      vesicle transport between cell compartments, Rho GTPases have emerged as critical
      players in membrane trafficking. Rho GTPase activity, actin remodeling, and
      phosphoinositide metabolism need to be coordinated in both space and time to
      ensure the progression of vesicles along membrane trafficking pathways. Although
      most molecular pathways are still unclear, in this review, we will highlight
      recent advances made in our understanding of how Rho-dependent signaling pathways
      organize actin dynamics and phosphoinositides and how phosphoinositides
      potentially provide negative feedback to Rho GTPases during endocytosis,
      exocytosis and membrane exchange between intracellular compartments. 

PMID- 24914543
TI  - Remote ischemic preconditioning protects against liver ischemia-reperfusion
      injury via heme oxygenase-1-induced autophagy.
AB  - BACKGROUND: Growing evidence has linked autophagy to a protective role of
      preconditioning in liver ischemia/reperfusion (IR). Heme oxygenase-1 (HO-1) is
      essential in limiting inflammation and preventing the apoptotic response to IR.
      We previously demonstrated that HO-1 is up-regulated in liver graft after remote
      ischemic preconditioning (RIPC). The aim of this study was to confirm that RIPC
      protects against IR via HO-1-mediated autophagy. METHODS: RIPC was performed with
      regional ischemia of limbs before liver ischemia, and HO-1 activity was inhibited
      pre-operation. Autophagy was assessed by the expression of light chain 3-II (LC3
      II). The HO-1/extracellular signal-related kinase (ERK)/p38/mitogen-activated
      protein kinase (MAPK) pathway was detected in an autophagy model and mineral oil
      induced IR in vitro. RESULTS: In liver IR, the expression of LC3-II peaked 12-24
      h after IR, and the ultrastructure revealed abundant autophagosomes in
      hepatocytes after IR. Autophagy was inhibited when HO-1 was inactivated, which we
      believe resulted in the aggravation of liver IR injury (IRI) in vivo. Hemin
      induced autophagy also protected rat hepatocytes from IRI in vitro, which was
      abrogated by HO-1 siRNA. Phosphorylation of p38-MAPK and ERK1/2 was up-regulated
      in hemin-pretreated liver cells and down-regulated after treatment with HO-1
      siRNA. CONCLUSIONS: RIPC may protect the liver from IRI by induction of HO-1/p38
      MAPK-dependent autophagy.

PMID- 24914545
TI  - Spatial design of hearing AIDS incorporating multiple vents.
AB  - The main aim of this study was to investigate the shape variation in the human
      ear canal and the effects of venting on the spatial design of hearing aids. The
      second aim was to determine the design feasibility of a multiple venting hearing
      aid and assess the flexibility of design provided. A statistical shape model
      based on principal component analysis was created from a dataset of 60 left and
      49 right ears. The modal variations of these models were then examined to
      determine the narrowest portion of the ear canal likely to limit effective
      venting. Finally, 3D models of two hearing aid shells, one with multiple 0.4-mm
      vents and the other with a single large 3-mm vent were created. Results showed
      that more than 50% of the shape variation in the human ear canal can be described
      by the first three modes of the statistical shape model developed. The narrowest
      predicted variation of this model had a minimum area of 36.4 mm(2), and the mean
      ear shape was found to have a minimum area of approximately 48 mm(2). It is
      estimated that even with a conservative vent packing of 0.4, multiple venting
      equivalent to at least a single 2-mm vent is achievable. The predicted variation
      in the human ear canal provides adequate physical space for a feasible multiple
      vented hearing aid shell. Furthermore, as multiple small vents are able to fit in
      around other components in the hearing aid design, certain design flexibility is
      provided by this venting approach. 

PMID- 24914544
TI  - Integrative analyses of hepatic differentially expressed genes and blood
      biomarkers during the peripartal period between dairy cows overfed or restricted
      fed energy prepartum.
AB  - Using published dairy cattle liver transcriptomics dataset along with novel blood
      biomarkers of liver function, metabolism, and inflammation we have attempted an
      integrative systems biology approach applying the classical functional enrichment
      analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA), and an
      upstream gene network analysis using Ingenuity Pathway Analysis (IPA).
      Transcriptome data was generated from experiments evaluating the impact of
      prepartal plane of energy intake [overfed (OF) or restricted (RE)] on liver of
      dairy cows during the peripartal period. Blood biomarkers uncovered that RE vs.
      OF led to greater prepartal liver distress accompanied by a low-grade
      inflammation and larger proteolysis (i.e., higher haptoglobin, bilirubin, and
      creatinine). Post-partum the greater bilirubinaemia and lipid accumulation in OF
      vs. RE indicated a large degree of liver distress. The re-analysis of microarray
      data revealed that expression of >4,000 genes was affected by diet * time. The
      bioinformatics analysis indicated that RE vs. OF cows had a liver with a greater
      lipid and amino acid catabolic capacity both pre- and post-partum while OF vs. RE
      cows had a greater activation of pathways/functions related to triglyceride
      synthesis. Furthermore, RE vs. OF cows had a larger (or higher capacity to cope
      with) ER stress likely associated with greater protein synthesis/processing, and
      a higher activation of inflammatory-related functions. Liver in OF vs. RE cows
      had a larger cell proliferation and cell-to-cell communication likely as a
      response to the greater lipid accumulation. Analysis of upstream regulators
      indicated a pivotal role of several lipid-related transcription factors (e.g.,
      PPARs, SREBPs, and NFE2L2) in priming the liver of RE cows to better face the
      early postpartal metabolic and inflammatory challenges. An all-encompassing
      dynamic model was proposed based on the findings. 

PMID- 24914546
TI  - Use of the interRAI CHESS scale to predict mortality among persons with
      neurological conditions in three care settings.
AB  - BACKGROUND: Persons with certain neurological conditions have higher mortality
      rates than the population without neurological conditions, but the risk factors
      for increased mortality within diagnostic groups are less well understood. The
      interRAI CHESS scale has been shown to be a strong predictor of mortality in the
      overall population of persons receiving health care in community and
      institutional settings. This study examines the performance of CHESS as a
      predictor of mortality among persons with 11 different neurological conditions.
      METHODS: Survival analyses were done with interRAI assessments linked to
      mortality data among persons in home care (n = 359,940), complex continuing care
      hospitals/units (n = 88,721), and nursing homes (n = 185,309) in seven Canadian
      provinces/territories. RESULTS: CHESS was a significant predictor of mortality in
      all 3 care settings for the 11 neurological diagnostic groups considered after
      adjusting for age and sex. The distribution of CHESS scores varied between
      diagnostic groups and within diagnostic groups in different care settings.
      CONCLUSIONS: CHESS is a valid predictor of mortality in neurological populations
      in community and institutional care. It may prove useful for several clinical,
      administrative, policy-development, evaluation and research purposes. Because it
      is routinely gathered as part of normal clinical practice in jurisdictions (like
      Canada) that have implemented interRAI assessment instruments, CHESS can be
      derived without additional need for data collection.

PMID- 24914548
TI  - Increased cystic fibrosis transmembrane conductance regulators expression and
      decreased epithelial sodium channel alpha subunits expression in early abortion:
      findings from a mouse model and clinical cases of abortion.
AB  - The status of the maternal endometrium is vital in regulating humoral homeostasis
      and for ensuring embryo implantation. Cystic fibrosis transmembrane conductance
      regulators (CFTR) and epithelial sodium channel alpha subunits (ENaC-alpha) play
      an important role in female reproduction by maintaining humoral and cell
      homeostasis. However, it is not clear whether the expression levels of CFTR and
      ENaC-alpha in the decidual component during early pregnancy are related with
      early miscarriage. CBA*DBA/2 mouse mating has been widely accepted as a classical
      model of early miscarriage. The abortion rate associated with this mating was
      33.33% in our study. The decidua of abortion-prone CBA female mice (DBA/2 mated)
      had higher CFTR mRNA and protein expression and lower ENaC-alpha mRNA and protein
      expression, compared to normal pregnant CBA mice (BLAB/C mated). Furthermore,
      increased CFTR expression and decreased ENaC-alpha expression were observed in
      the uterine tissue from women with early miscarriage, as compared to those with
      successful pregnancy. In conclusion, increased CFTR expression and decreased ENaC
      alpha expression in the decidua of early abortion may relate with failure of
      early pregnancy. 

PMID- 24914550
TI  - Unravelling the paradox of loss of genetic variation during invasion: superclones
      may explain the success of a clonal invader.
AB  - Clonality is a common characteristic of successful invasive species, but general
      principles underpinning the success of clonal invaders are not established. A
      number of mechanisms could contribute to invasion success including clones with
      broad tolerances and preferences, specialist clones and adaptation in situ. The
      majority of studies to date have been of plants and some invertebrate
      parthenogens, particularly aphids, and have not necessarily caught invasion at
      very early stages. Here we describe the early stages of an invasion by a Northern
      Hemisphere Hymenopteran model in three different land masses in the Southern
      Hemisphere. Nematus oligospilus Forster (Hymenoptera: Tenthredinidae), a sawfly
      feeding on willows (Salix spp.), was recently introduced to the Southern
      Hemisphere where it has become invasive and is strictly parthenogenetic. In this
      study, the number of N. oligospilus clones, their distribution in the landscape
      and on different willow hosts in South Africa, New Zealand and Australia were
      assessed using 25 microsatellite markers. Evidence is presented for the presence
      of two very common and widespread multilocus genotypes (MLGs) or 'superclones'
      dominating in the three countries. Rarer MLGs were closely related to the most
      widespread superclone; it is plausible that all N. oligospilus individuals were
      derived from a single clone. A few initial introductions to Australia and New
      Zealand seemed to have occurred. Our results point towards a separate
      introduction in Western Australia, potentially from South Africa. Rarer clones
      that were dominant locally putatively arose in situ, and might be locally
      favoured, or simply have not yet had time to spread. Data presented represent
      rare baseline data early in the invasion process for insights into the mechanisms
      that underlie the success of a global invader, and develop Nematus oligospilus as
      a valuable model to understand invasion genetics of clonal pests. 

PMID- 24914551
TI  - Impact of host IL28B rs12979860, rs8099917 in interferon responsiveness and
      advanced liver disease in chronic genotype 3 hepatitis C patients.
AB  - BACKGROUND AND AIMS: Genetic polymorphisms near interleukin 28B gene are
      associated with spontaneous and treatment induced clearance of hepatitis C virus
      (HCV). Our objective was to evaluate the impact of interleukin 28B single
      nucleotide polymorphism (rs12979860, rs8099917) variability in HCV genotype 3
      infected populations. METHODS: 400 hepatitis C seroreactive patients from
      different population groups in Eastern and North Eastern part of India were
      assessed for host and viral genotypic analysis. 83 HCV genotype 3 infected
      patients were administered pegylated interferon- ribavirin therapy. Viral
      genotyping was performed using nested reverse transcriptase-PCR followed by
      direct sequencing methods. Host interleukin 28B genotyping was performed using
      real-time PCR based single nucleotide polymorphism analysis. RESULTS: Out of 400
      hepatitis C seroreactive individuals, 73.25% were found to be RNA positive. HCV
      genotype 3 (65.87%) was found to be the major circulating strain in this region
      followed by genotype 1 (32.08%). rs12979860 CC genotype was significantly
      associated with sustained virological response in HCV genotype 3 infected
      population. In patients achieving rapid virological response, favourable CC/TT
      allele at rs12979860, rs8099917 was found to be predominant at both the alleles
      at 77%, 73.2% respectively; whereas in case of patients with relapsed HCV
      infection CT, TG alleles were found to be predominant. Additionally, CC genotypes
      at rs12979860 were found to be associated with sustained virological response in
      patients with high viral load (OR = 6.75, 0.05<p). HCV unfavourable rs12979860
      TT, rs8099917 GG alleles were present in 34%, 27.6% patients with relapsed HCV
      infection respectively. Also unfavourable CT, TG genotypes were found to be
      predominant in patients with advanced stages of liver disease. CONCLUSION: CC, TT
      the two favourable markers at SNPs rs12979860 and rs8099917 are strongly
      associated with sustained virological response in genotype 3 infected
      populations. This information will aid clinicians to effectively design response
      based treatment regimen.

PMID- 24914549
TI  - Changes in QTc interval in the citalopram for agitation in Alzheimer's disease
      (CitAD) randomized trial.
AB  - BACKGROUND: A Food and Drug Administration (FDA) safety communication in August
      2011 warned that citalopram was associated with a dose dependent risk of QT
      prolongation and recommended dose restriction in patients over the age of 60 but
      did not provide data for this age group. METHODS: CitAD was a randomized, double
      masked, placebo-controlled, multicenter clinical trial for agitation in
      Alzheimer's disease (AD). Participants were assigned to citalopram (target dose
      of 30 mg/day) or placebo in a 1 ? 1 ratio. 186 people, 181 of whom were over the
      age of 60, having probable AD with clinically significant agitation were
      recruited from September 2009 to January 2013. After the FDA safety communication
      about citalopram, ECG was added to the required study procedures before
      enrollment and repeated at week 3 to monitor change in QTc interval. Forty-eight
      participants were enrolled after enhanced monitoring began. RESULTS: Citalopram
      treatment was associated with a larger increase in QTc interval than placebo
      (difference in week 3 QTc adjusting for baseline QTc: 18.1 ms [95% CI: 6.1,
      30.1]; p = 0.004). More participants in the citalopram group had an increase >=
      30 ms from baseline to week 3 (7 in citalopram versus 1 in placebo; Fisher's
      exact p = 0.046), but only slightly more in the citalopram group met a gender
      specific threshold for prolonged QTc (450 ms for males; 470 ms for females) at
      any point during follow-up (3 in citalopram versus 1 in placebo, Fisher's exact p
      = 0.611). One of the citalopram participants who developed prolonged QTc also
      displayed ventricular bigeminy. No participants in either group had a
      cardiovascular-related death. CONCLUSION: Citalopram at 30 mg/day was associated
      with improvement in agitation in patients with AD but was also associated with QT
      prolongation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00898807.

PMID- 24914552
TI  - Severe eczema in infancy can predict asthma development. A prospective study to
      the age of 10 years.
AB  - BACKGROUND: Children with atopic eczema in infancy often develop allergic
      rhinoconjunctivitis and asthma, but the term "atopic march" has been questioned
      as the relations between atopic disorders seem more complicated than one
      condition progressing into another. OBJECTIVE: In this prospective multicenter
      study we followed children with eczema from infancy to the age of 10 years
      focusing on sensitization to allergens, severity of eczema and development of
      allergic airway symptoms at 4.5 and 10 years of age. METHODS: On inclusion, 123
      children were examined. Hanifin-Rajka criteria and SCORAD index were used to
      describe the eczema. Episodes of wheezing were registered, skin prick tests and
      IgE tests were conducted and questionnaires were filled out. Procedures were
      repeated at 4.5 and 10 years of age with additional examinations for ARC and
      asthma. RESULTS: 94 out of 123 completed the entire study. High SCORAD points on
      inclusion were correlated with the risk of developing ARC, (B = 9.86, P = 0.01)
      and asthma, (B = 10.17, P = 0.01). For infants with eczema and wheezing at the
      first visit, the OR for developing asthma was 4.05(P = 0.01). ARC at 4.5 years of
      age resulted in an OR of 11.28(P = 0.00) for asthma development at 10 years.
      CONCLUSION: This study indicates that infant eczema with high SCORAD points is
      associated with an increased risk of asthma at 10 years of age. Children with
      eczema and wheezing episodes during infancy are more likely to develop asthma
      than are infants with eczema alone. Eczema in infancy combined with early onset
      of ARC seems to indicate a more severe allergic disease, which often leads to
      asthma development. The progression from eczema in infancy to ARC at an early age
      and asthma later in childhood shown in this study supports the relevance of the
      term "atopic march", at least in more severe allergic disease.

PMID- 24914553
TI  - New high-affinity monoclonal antibodies against Shiga toxin 1 facilitate the
      detection of hybrid Stx1/Stx2 in vivo.
AB  - BACKGROUND: Shiga toxin-producing E. coli (STEC) are a group of common and
      potentially deadly intestinal pathogens expressing Shiga toxin (Stx) as a primary
      virulence factor. Of the two types of Stx, Stx2 is responsible for more severe
      symptoms during infection, while Stx1 is almost identical to the Shiga toxin from
      Shigella dysenteriae, a ubiquitous pathogen in developing countries. Although
      antibodies against Stx1 have been reported, few have reached the affinity needed
      for assembling highly sensitive immunoassays. Sensitive and affordable
      immunoassays for Stx1 and Stx2 could help improve detection of STEC in livestock,
      food, the environment, and in clinical samples resulting in improved food safety
      and human health. METHOD AND FINDINGS: Three new monoclonal antibodies (mAbs)
      against the B subunit of Stx1 were generated using recombinant toxoid Stx1E167Q
      and hybridoma technology. These new mAbs recognize all subtypes of Stx1, but do
      not cross-react with any subtype of Stx2. In addition, they exhibited the ability
      to neutralize Stx1 toxicity in Vero cell assays. An optimized sandwich ELISA
      using of a pair of these mAbs had a limit of detection of 8.7 pg/mL, which is
      superior to any existing assay of this kind. Using one of these Stx1 mAbs in
      concert with Stx2 mAbs, the presence of hybrid Stx1/Stx2 toxin in the culture
      media of STEC strains that express both Stx1 and Stx2 was demonstrated.
      CONCLUSIONS: These new mAbs provide a mix of availability, utility, versatility,
      and most importantly, increased sensitivity for detection of Stx1. There are
      numerous potential applications for these mAbs, including low-cost detection
      assays and therapeutic use. Analysis of hybrid Stx1/2 could provide new insights
      on the structure, activity, and cellular targets of Shiga toxins.

PMID- 24914554
TI  - Extensive behavioural divergence following colonisation of the freshwater
      environment in threespine sticklebacks.
AB  - Colonisation of novel environments means facing new ecological challenges often
      resulting in the evolution of striking divergence in phenotypes. However, little
      is known about behavioural divergence following colonisation, despite the
      predicted importance of the role of behavioural phenotype-environment
      associations in adaptive divergence. We studied the threespine stickleback
      (Gasterosteus aculeatus), a model system for postglacial colonisation of
      freshwater habitats largely differing in ecological conditions from the ones
      faced by the descendants of the marine ancestor. We found that common-environment
      reared freshwater juveniles were less social, more active and more aggressive
      than their marine counterparts. This behavioural divergence could represent the
      result of natural selection that acted on individuals following freshwater
      colonisation, with predation as a key selection agent. Alternatively, the
      behavioural profile of freshwater juveniles could represent the characteristics
      of individuals that preferentially invaded freshwater after the glacial retreat,
      drawn from the standing variation present in the marine population. 

PMID- 24914555
TI  - LINE-1 of evidence for fetal oocyte attrition by retrotransposon.
AB  - Fetal oocytes in mammals undergo extensive apoptosis during development. In this
      issue of Developmental Cell, Malki et al. (2014) provide insight into how and why
      such massive oocyte loss occurs through the demonstration that the expression
      level of LINE-1 retrotransposon defines the survival threshold and thus viability
      of fetal oocytes.

PMID- 24914556
TI  - DMRT1 keeps masculinity intact.
AB  - It is generally assumed that sexual phenotypes formed in utero are permanently
      established and do not require maintenance. In this issue of Developmental Cell,
      Minkina et al. (2014) now show that the transcriptional regulator DMRT1 actively
      prevents postnatal male-to-female sex reversal by blocking the activation of
      retinoid-signaling-dependent feminization genes.

PMID- 24914557
TI  - Directing traffic and autophagy in axonal transport.
AB  - In this issue of Developmental Cell, Fu et al. (2014) address what determines
      persistent directional movement along microtubules of organelles capable of
      bidirectional transit. They show that retrograde axonal autophagosome transport
      is mediated by the scaffolding protein JIP1, which not only inhibits anterograde
      movement but may also promote autophagosome maturation.

PMID- 24914558
TI  - Actin cytoskeleton reorganization by Syk regulates Fcgamma receptor
      responsiveness by increasing its lateral mobility and clustering.
AB  - Clustering of immunoreceptors upon association with multivalent ligands triggers
      important responses including phagocytosis, secretion of cytokines, and
      production of immunoglobulins. We applied single-molecule detection and tracking
      methods to study the factors that control the mobility and clustering of
      phagocytic Fcgamma receptors (FcgammaR). While the receptors exist as monomers in
      resting macrophages, two distinct populations were discernible based on their
      mobility: some diffuse by apparent free motion, while others are confined within
      submicron boundaries that reduce the frequency of spontaneous collisions. Src
      family and Syk kinases determine the structure of the actin cytoskeleton, which
      is fenestrated, accounting for the heterogeneous diffusion of the FcgammaR.
      Stimulation of these kinases during phagocytosis induces reorganization of the
      cytoskeleton both locally and distally in a manner that alters receptor mobility
      and clustering, generating a feedback loop that facilitates engagement of
      FcgammaR at the tip of pseudopods, directing the progression of phagocytosis.

PMID- 24914559
TI  - Mechanism of cytokinetic contractile ring constriction in fission yeast.
AB  - Cytokinesis involves constriction of a contractile actomyosin ring. The
      mechanisms generating ring tension and setting the constriction rate remain
      unknown because the organization of the ring is poorly characterized, its tension
      was rarely measured, and constriction is coupled to other processes. To isolate
      ring mechanisms, we studied fission yeast protoplasts, in which constriction
      occurs without the cell wall. Exploiting the absence of cell wall and actin
      cortex, we measured ring tension and imaged ring organization, which was dynamic
      and disordered. Computer simulations based on the amounts and biochemical
      properties of the key proteins showed that they spontaneously self-organize into
      a tension-generating bundle. Together with rapid component turnover, the self
      organization mechanism continuously reassembles and remodels the constricting
      ring. Ring constriction depended on cell shape, revealing that the ring operates
      close to conditions of isometric tension. Thus, the fission yeast ring sets its
      own tension, but other processes set the constriction rate.

PMID- 24914560
TI  - A dynamic microtubule cytoskeleton directs medial actomyosin function during tube
      formation.
AB  - The cytoskeleton is a major determinant of cell-shape changes that drive the
      formation of complex tissues during development. Important roles for actomyosin
      during tissue morphogenesis have been identified, but the role of the microtubule
      cytoskeleton is less clear. Here, we show that during tubulogenesis of the
      salivary glands in the fly embryo, the microtubule cytoskeleton undergoes major
      rearrangements, including a 90 degrees  change in alignment relative to the
      apicobasal axis, loss of centrosomal attachment, and apical stabilization.
      Disruption of the microtubule cytoskeleton leads to failure of apical
      constriction in placodal cells fated to invaginate. We show that this failure is
      due to loss of an apical medial actomyosin network whose pulsatile behavior in
      wild-type embryos drives the apical constriction of the cells. The medial
      actomyosin network interacts with the minus ends of acentrosomal microtubule
      bundles through the cytolinker protein Shot, and disruption of Shot also impairs
      apical constriction.

PMID- 24914563
TI  - Evaluation of body surface area formulae for scaling GFR of adult renal patients:
      more between-subject variability explained by the DuBois & DuBois formula.
AB  - BACKGROUND: Scaling glomerular filtration rate (GFR) to body surface area (BSA)
      has been widely accepted, and was debated in recent years. Although the
      indexation ability of BSA is inferior to other physiological variables, the
      evaluation of BSA formulae is still meaningful to clinical practice. In this
      study, to evaluate the indexation ability of BSA formulae, the repeated measures
      analyses of camera-based scintigraphy (Gates method, gGFR) and plasma-based
      clearance (pGFR) were used to specially focus on the between-subject variability
      that tried to be minimized by GFR normalization. METHODS: The patients, who were
      older than 18 y and suffered from renal diseases, were enrolled and grouped
      according to the Chinese BMI (body mass index) criteria. All patients accepted
      renal scintigraphy and plasma clearance examinations. The gGFR and pGFR were
      separately scaled to DuBois & DuBois, Boyd, Stevenson, Gehan, Haycock, Mosteller,
      Hu and Livingston and Lee's formula. In the repeated measures analyses, the
      intraclass correlation coefficient (ICC), concordance correlation coefficient
      (CCC) and the ratio of residual standard deviation to pooled standard deviation
      (RSD/PSD) were used for the evaluation. RESULTS: During January 2010 and May
      2012, 220 patients were enrolled. The evaluated BSA formulae had well correlated
      results and significant differences among BMI groups. From high to low, the
      sequence of the correlation between BMI and BSA formula was L-L, Haycock, Gehan,
      Boyd, Mosteller, Stevenson, Hu and DuBois & DuBois formula. Both the scaled
      indices (ICC and CCC) and RSD/PSD indicated that, the sequence of indexation
      ability of BSA equations was Livingston < Haycock < Gehan < Stevenson < Mosteller
      < Boyd < Hu < DuBois & DuBois. CONCLUSIONS: Among the evaluated BSA formulae,
      DuBois & DuBois formula correlates to BMI the worst, and has the best indexation
      ability in scaling GFR of adult renal patients.

PMID- 24914561
TI  - LC3 binding to the scaffolding protein JIP1 regulates processive dynein-driven
      transport of autophagosomes.
AB  - Autophagy is essential for maintaining cellular homeostasis in neurons, where
      autophagosomes undergo robust unidirectional retrograde transport along axons. We
      find that the motor scaffolding protein JIP1 binds directly to the autophagosome
      adaptor LC3 via a conserved LIR motif. This interaction is required for the
      initial exit of autophagosomes from the distal axon, for sustained retrograde
      transport along the midaxon, and for autophagosomal maturation in the proximal
      axon. JIP1 binds directly to the dynein activator dynactin but also binds to and
      activates kinesin-1 in a phosphorylation-dependent manner. Following JIP1
      depletion, phosphodeficient JIP1-S421A rescues retrograde transport, while
      phosphomimetic JIP1-S421D aberrantly activates anterograde transport. During
      normal autophagosome transport, residue S421 of JIP1 may be maintained in a
      dephosphorylated state by autophagosome-associated MKP1 phosphatase. Moreover,
      binding of LC3 to JIP1 competitively disrupts JIP1-mediated activation of
      kinesin. Thus, dual mechanisms prevent aberrant activation of kinesin to ensure
      robust retrograde transport of autophagosomes along the axon.

PMID- 24914562
TI  - Effect of developmental stage of HSC and recipient on transplant outcomes.
AB  - The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice
      arise in the aorta-gonad-mesonephros (AGM) on embryonic day 11.5 (E11.5).
      However, at this stage, there is a discrepancy between the apparent frequency of
      HSCs depicted with imaging and their rarity when measured with limiting dilution
      transplant. We have attempted to reconcile this difference using neonatal
      recipients, which are more permissive for embryonic HSC engraftment. We found
      that embryonic HSCs from E9.5 and E10.5 preferentially engrafted neonates,
      whereas developmentally mature, definitive HSCs from E14.5 fetal liver or adult
      bone marrow (BM) more robustly engrafted adults. Neonatal engraftment was
      enhanced after treating adult BM-derived HSCs with interferon. Adult BM-derived
      HSCs preferentially homed to the liver in neonatal mice yet showed balanced
      homing to the liver and spleen in adults. These findings emphasize the functional
      differences between nascent and mature definitive HSCs.

PMID- 24914564
TI  - A typology of interpartner conflict and maternal parenting practices in high-risk
      families: examining spillover and compensatory models and implications for child
      adjustment.
AB  - The present study incorporates a person-based approach to identify spillover and
      compartmentalization patterns of interpartner conflict and maternal parenting
      practices in an ethnically diverse sample of 192 2-year-old children and their
      mothers who had experienced higher levels of socioeconomic risk. In addition, we
      tested whether sociocontextual variables were differentially predictive of theses
      profiles and examined how interpartner-parenting profiles were associated with
      children's physiological and psychological adjustment over time. As expected,
      latent class analyses extracted three primary profiles of functioning: adequate
      functioning, spillover, and compartmentalizing families. Furthermore,
      interpartner-parenting profiles were differentially associated with both
      sociocontextual predictors and children's adjustment trajectories. The findings
      highlight the developmental utility of incorporating person-based approaches to
      models of interpartner conflict and maternal parenting practices. 

PMID- 24914565
TI  - Additional Tension Screws Improve Stability in Elastic Stable Intramedullary
      Nailing: Biomechanical Analysis of a Femur Spiral Fracture Model.
AB  - PURPOSE: For pediatric femoral shaft fractures, elastic stable intramedullary
      nailing (ESIN) is an accepted method of treatment. But problems regarding
      stability with shortening or axial deviation are well known in complex fracture
      types and heavier children. Biomechanical in vitro testing was performed to
      determine whether two modified osteosyntheses with an additional tension screw
      fixation or screw fixation alone without nails could significantly improve the
      stability in comparison to classical ESIN. METHODS: A total of 24 synthetic
      adolescent-sized femoral bone models (Sawbones, 4th generation; Vashon,
      Washington, United States) with an identical spiral fracture (length 100 mm) were
      used. All grafts underwent retrograde fixation with two C-shaped steel nails
      (2C). Of the 24, 8 osteosyntheses were supported by one additional tension screw
      (2C1S) and another 8 by two screws (2S) in which the intramedullary nails were
      removed before testing. Each configuration underwent biomechanical testing in 4
      point bending, external rotation (ER) and internal rotation (IR). Furthermore,
      the modifications were tested in axial physiological 9 degrees position for
      shifting and dynamic compression as well as dynamic load. RESULTS: Both screw
      configurations (2C1S and 2S) demonstrated a significantly higher stability in
      comparison to the 2C configuration in 4-point bending (anterior-posterior, 0.95
      Nm/mm [2C] < 8.41 Nm/mm [2C1S] and 15.12 Nm/mm [2S]; posterior-anterior, 8.55
      Nm/mm [2C] < 12.65 Nm/mm [2C1S] and 17.54 Nm/mm [2S]; latero-medial, 1.17 Nm/mm
      [2C] < 5.53 Nm/mm [2C1S] and 9.15 Nm/mm [2S]; medio-lateral, 1.74 Nm/mm [2C] <
      9.69 Nm/mm [2C1S] and 12.20 Nm [2S]; all p < 0.001) and during torsion (ER, 0.61
      Nm/degree [2C] < 4.10 Nm/degree [2C1S] and 9.29 Nm/degree [2S]; IR, 0.18
      Nm/degree [2C] < 6.17 Nm/degree [2C1S] and 10.61 Nm/degree [2S]; all p < 0.001].
      The shifting in compression in 9 degrees position was only slightly influenced.
      The comparison of 2S versus 2C1S showed more stability for 2S than 2C1S in all
      testing, except the axial 9 degrees compression tests for shifting. In contrast
      to the 2C configuration, both modifications (2C1S and 2S) turned out to be stable
      in dynamic 9 degrees axial compression with a force of 100 up to 1,000 N at 2.5
      Hz in 250,000 load cycles. CONCLUSIONS: In this in vitro adolescence femur spiral
      fracture model, the stability of ESIN could be significantly improved by two
      modifications with additional tension screws. If transferred in clinical
      practice, these modifications might offer earlier weight bearing and less
      problems of shortening or axial deviation.

PMID- 24914566
TI  - Telephonic advance care planning facilitated by health plan case managers.
AB  - OBJECTIVE: The insurance plan case managers (CMs) of Priority Health, part of a
      regional healthcare system located in Michigan, work telephonically with frail
      patients who have multiple comorbidities. However, these CMs have lacked
      facilitation skills for advance care planning (ACP) discussions in this
      vulnerable population. In 2012, the findings of a six-month pilot study of
      telephonic ACP (TACP) with some of the plan's Medicare population were
      implemented with Medicare members under case management. METHOD: Case mangers
      were trained and certified by Respecting Choices(r) to introduce and facilitate
      ACP discussions telephonically utilizing both First Steps and Last Steps
      protocols. The CMs identified appropriate patients using hospitalization and
      emergency room utilization data, severity of illness, and diagnostic criteria.
      The primary goal was to complete both the ACP discussion and the documentation
      for each protocol on identified patients. They also attempted to schedule
      facilitated conversations with the patients' healthcare advocates present.
      RESULTS: During a 12-month period, 576 health plan members were offered First
      Steps discussions, with 198 interested in engaging in further ACP. Some 152
      members were identified for Last Steps TACP using established criteria;
      discussions occurred with 56 members. TACP implementation resulted in 55 new or
      updated First Steps documents and 4 Last Steps documents. A total of 50
      discussions included the designated healthcare advocate. SIGNIFICANCE OF RESULTS:
      Following TACP implementation with the Medicare CM team and evaluation of the
      results, processes and methods were instituted to increase engagement and
      completion of discussions and documents. These included enhancements to the
      electronic assessment and ongoing support of the CM team to increase the
      engagement of patients and advocates. Dissemination of the project to the entire
      Medicare CM team demonstrated opportunities and lessons learned for facilitated
      TACP discussions. The TACP model has the potential to be successfully utilized by
      other health insurance companies.

PMID- 24914567
TI  - Blood pressure effects of glucagon-like peptide 1 analogues and sodium glucose
      transporter 2 inhibitors.
AB  - PURPOSE OF REVIEW: The growing number of obese patients with a high risk of
      developing hypertension and type 2 diabetes mellitus requires several drugs to
      treat all the associated morbidities. Ideally, one drug would help to tackle
      several health problems at the same time. We review available information on the
      blood pressure-reducing effects of the new antidiabetic drug classes, glucagon
      like peptide 1 analogues and sodium glucose transporter 2 inhibitors. RECENT
      FINDINGS: Blood pressure reduction with glucagon-like peptide 1 analogues or
      sodium glucose transporter 2 inhibitors ranges between 1 and 7 mmHg, both
      systolic and diastolic. As these drugs have not been sufficiently investigated in
      studies with office or ambulatory blood pressure as the primary efficacy measure
      or in prespecified hypertensive patient populations, their true efficacy in
      reducing blood pressure remains unclear. These studies are needed because the
      blood pressure-lowering effects of metabolic drugs may help to improve the
      clinical management of hypertensive patients with type 2 diabetes mellitus.
      SUMMARY: Obese patients with type 2 diabetes mellitus and difficult to control
      arterial hypertension represent a clinically important patient group at high
      cardiovascular risk that may profit from combined cardiovascular and metabolic
      actions of a drug.

PMID- 24914568
TI  - Association of anti-human leukocyte antigen and anti-angiotensin II type 1
      receptor antibodies with liver allograft fibrosis after immunosuppression
      withdrawal.
AB  - BACKGROUND: Many pediatric patients who receive a living-donor liver transplant
      undergo withdrawal of immunosuppression (IS). For them, the high incidence of
      long-term progressive graft fibrosis is of particular concern. METHODS: We
      conducted a cross-sectional study including 81 pediatric patients who underwent
      IS withdrawal after living-donor liver transplant at Kyoto University Hospital
      and whose serum samples and pathological data could be obtained during the
      analysis period. We examined the association of donor-specific anti-human
      leukocyte antigen (HLA) antibody (DSA) and angiotensin II type 1 receptor
      antibody (anti-AT1R Ab) with posttransplant graft fibrosis. Normalized mean
      fluorescence intensity (MFI) 5,000 or higher and anti-AT1R Ab concentrations 17
      U/mL or higher were both considered high level. The patients were classified into
      an advanced fibrosis group (AFG) (Ishak score >= 3) and a control group (CG)
      (Ishak score <= 2). RESULTS: Only one patient demonstrated DSA class I. Among
      those who demonstrated DSA class II, more AFG patients than CG patients
      demonstrated high-level mean fluorescence intensity, although the difference was
      not significant (64% vs. 39%; P=0.053). The incidence of high-level DSA-DRB1,
      however, was significantly higher in the AFG than that in the CG (40% vs. 4%;
      P<0.001), but there was no significant difference in DSA-DQB1 or DSA-DRB345. High
      level anti-AT1R Ab was significantly more frequent in the AFG than in the CG (65%
      vs. 36%; P=0.02). All patients with both high-level DSA-DRB1 and high-level anti
      AT1R Ab were found to have advanced fibrosis (P<0.001). CONCLUSION: Anti-AT1R Ab
      and DSA-DRB1 may be candidates as biomarkers of graft fibrosis; both HLA and non
      HLA immunity may be involved in graft fibrosis after IS withdrawal.

PMID- 24914569
TI  - Solid organ transplant donors with central nervous system infection.
AB  - BACKGROUND: While donor-derived infections (DDI) remain uncommon, multiple
      reports describe DDI with pathogens that cause central nervous system (CNS)
      infection resulting in significant recipient disease. The Ad Hoc Disease
      Transmission Advisory Committee (DTAC) reviewed the records of potential donor
      derived disease transmission events (PDDTE) to describe donor characteristics and
      outcomes associated with DDI from CNS pathogens. METHODS: All PDDTE reported from
      January 2008 to September 2010 were reviewed for characteristics suggesting CNS
      infection in the donor or the recipient. Identified cases were further examined
      to determine if donor CNS infection resulted in recipient infection. RESULTS:
      Ninety-one PDDTE cases in which there was concern for CNS infection in the donor
      or recipient were identified. Further review confirmed CNS infection in 12
      donors, six of whom transmitted infection to 10 of 15 exposed recipients with
      five recipient deaths. Pathogens included Balamuthia mandrillaris, Cryptococcus
      neoformans, lymphocytic choriomeningitis virus, and West Nile virus. Listed cause
      of death at procurement for these donors included stroke, anoxia, acute
      disseminated encephalomyelitis, and meningoencephalitis. Confounding diagnoses
      were present in 6 of 12 donors that would have allowed them to be considered at
      low risk of transmitting a CNS pathogen. Of the six donors with no confounding
      conditions, three exhibited at least two suspicious "DTAC warning criteria" for
      CNS infection. CONCLUSION: Careful clinical assessment of donors combined with a
      high index of suspicion for ambiguous or misleading findings associated with CNS
      infection can reduce, but not eliminate, DDI with CNS pathogens.

PMID- 24914570
TI  - Impact of recipient body mass index on short-term and long-term survival of
      pancreatic grafts.
AB  - BACKGROUND: The impact of recipient body mass index on graft and patient survival
      after pancreas transplantation is not well known. METHODS: We have analyzed data
      from all pancreas transplant recipients reported in the Scientific Registry of
      Transplant Recipients between 1987 and 2011. Recipients were categorized into BMI
      classes, as defined by the World Health Organization. Short-term (90 days) and
      long-term (90 days to 5 years) patient and graft survivals were analyzed
      according to recipient BMI class using Kaplan-Meier estimates. Hazard ratios were
      estimated using Cox proportional hazard models. RESULTS: A total of 21,075 adult
      recipients were included in the analysis. Mean follow-up was 5 +/- 1.1 years.
      Subjects were overweight or obese in 39%. Increasing recipient BMI was an
      independent predictor of pancreatic graft loss and patient death in the short
      term (P<0.001), especially for obese class II patient survival (hazard ratio,
      2.07; P=0.009). In the long term, obesity, but not overweight, was associated
      with higher risk of graft failure (P=0.01). Underweight was associated with a
      higher risk of long-term death (P<0.001). CONCLUSION: These results question the
      safety of pancreas transplantation in obese patients and suggest that they may be
      directed to alternate therapies, such as behavioral modifications or bariatric
      surgery, before pancreas transplantation is considered.

PMID- 24914571
TI  - Alloantibody to a Bw4 epitope in a Bw4+B*27: 05 patient.
AB  - BACKGROUND: Alloantibodies to the Bw4 epitope are known to be heterogeneous, but
      it is widely assumed that anti-Bw4 alloantibodies arise only in individuals who
      do not express a Bw4 epitope. METHODS: Bw4 expression was confirmed by DNA
      sequence analysis. Anti-Bw4 reactivity was confirmed by absorption with
      transfected cells. RESULTS: A Bw4 (B*27:05 or B*27:13) patient expressed antibody
      that bound all Bw4 human leukocyte antigen-A and human leukocyte antigen-B
      antigens tested, except B*27:05 and B*44:02. Serum absorbed with B*51:01
      transfected HYM2.C1R cells left only reactivity to B17 (B57, B58), but not to any
      other Bw4 antigens. CONCLUSION: A Bw4 patient made antibody to a Bw4 epitope.
      This finding indicates that apparent anti-Bw4 or anti-Bw6 antibody should not be
      ignored even in patients who express a common Bw4 or Bw6 antigen, respectively.

PMID- 24914572
TI  - Renal outcomes of liver transplant recipients who had pretransplant kidney
      biopsy.
AB  - BACKGROUND: Kidney biopsy has been recommended to guide kidney allocation in
      selected liver transplant (LT) candidates with renal dysfunction. However, post
      LT-alone renal outcomes in recipients who showed evidence of reversible renal
      injury and limited chronicity on pre-LT kidney biopsy are unclear. METHODS: Renal
      outcomes of 41 LT recipients who had pre-LT kidney biopsy for unexplained renal
      dysfunction, proteinuria, and hematuria were retrospectively reviewed. All
      biopsies showed less than 30% interstitial fibrosis and less than 30% to 40%
      glomerulosclerosis. Study endpoints were renal replacement therapy (RRT) at 1
      month and the need for kidney transplantation at 1 year from LT. RESULTS: Six
      patients were on RRT at time of biopsy. Median (range) iothalamate glomerular
      filtration rate and 24-hr urinary protein excretion for the remaining 35 patients
      were 29 (6-88) mL/min per 1.73 m(2) and 65 (0-4,338) mg/day, respectively.
      Glomerulonephritis and acute tubular necrosis were present in 28 (68%) and 16
      (39%) of the cases. Six patients (15%) did not recover kidney function at 1 month
      and RRT at time of LT was the only factor associated with this endpoint (P=0.04).
      Seven of the 31 (22%) patients with 1-year data met criteria for kidney
      transplantation within the first post-LT year. Surgical re-exploration was the
      only factor associated with the need for kidney transplantation at 1 year
      (P=0.05). CONCLUSIONS: The most LT recipients with minimal chronic changes on pre
      LT kidney biopsy recovered kidney function within 1 month from LT. A small but
      significant percentage met criteria for kidney transplantation at 1 year because
      of the development of unforeseen post-LT complications.

PMID- 24914573
TI  - Resveratrol in vitro ameliorates tert-butyl hydroperoxide-induced alterations in
      erythrocyte membranes from young and older humans.
AB  - Implication of reactive oxygen species/oxidative stress has been readily reported
      in etiology of aging and related manifestations. Plasma membrane as a regulator
      of numerous aspects of cell physiology including cell-cell interaction, solute
      transport, and signal transduction, provides structural integrity to the cells.
      The aim of the present study was to determine the effect of resveratrol
      administration in vitro, to evaluate the biological effect of this phytoalexin in
      oxidatively injured erythrocytes during aging. This study, carried out on 91
      normal healthy subjects, provides experimental evidence that erythrocytes have
      increased oxidative damage with age. In vitro administration of resveratrol
      significantly attenuated deleterious effects of oxidative injury in erythrocytes
      from humans of all ages. 

PMID- 24914574
TI  - A case study of modeling and exposure-response prediction for count data.
AB  - Even with two doses of an experimental drug in Phase III studies, with the
      commonly used approach for assessing treatment effects of individual doses, it
      may still be difficult to determine the final commercial dose. In such a
      scenario, with plasma concentration data collected in the studies, a modeling
      approach can be applied to predict treatment effects at different plasma
      concentration levels. Through an established relationship between plasma
      concentration and dose, the treatment effects of doses not studied in the Phase
      III studies can then be predicted. The results can further be applied to justify
      the final dose confirmation or selection. In this article, a Phase III program
      example with count data as the primary endpoint in the multiple sclerosis area is
      used to illustrate the application of such a technique for dose confirmation.
      Several models, such as the overdispersion Poisson model, negative binomial
      model, and recurrent event models, are considered. The negative binomial model is
      preferable due to better data fitting and the capability of within-treatment
      assessment and between-treatment comparison. 

PMID- 24914575
TI  - Concurrent performance of a cognitive and dynamic obstacle avoidance task:
      influence of dual-task training.
AB  - The performance of 2 or more attention demanding tasks simultaneously is poorly
      understood. The purpose of the study was to investigate optimal practice
      strategies for performing 2 simultaneous tasks. Eighteen young adults walked and
      stepped over either a static or dynamic obstacle, while responding to an auditory
      Stroop test. Participants were randomly assigned to 1 of 3 groups: one that
      practiced both tasks simultaneously, practiced only the cognitive task, or
      received no practice. Results indicate that only the dual-task practice group
      showed significantly more improvement in the locomotor task through reduced
      variability of gait velocity, obstacle clearance, and takeoff distance. Findings
      demonstrate that the practice of two concurrent, attention demanding tasks
      results in the best performance improvement for both tasks.

PMID- 24914576
TI  - Moderate and late preterm birth: effect on brain size and maturation at term
      equivalent age.
AB  - PURPOSE: To compare the size of multiple brain structures, maturation in terms of
      both brain myelination and gyral development, and evidence of brain injury
      between moderate and late preterm (MLPT) and term-born infants at term-equivalent
      age. MATERIALS AND METHODS: The study was approved by the human research ethics
      committees of the participating hospitals, and informed parental consent was
      obtained for all infants. One hundred ninety-nine MLPT and 50 term-born infants
      underwent 3-T magnetic resonance (MR) imaging brain examinations at 38-44 weeks
      of corrected gestational age. T1- and T2-weighted MR images were compared between
      groups for size of multiple cerebral structures, degree of myelination in the
      posterior limb of the internal capsule, gyral maturation, signal intensity
      abnormalities, and presence of cysts by a single assessor who was blinded to the
      gestational group and perinatal course of the infants. Group differences were
      compared by using linear regression for continuous variables and logistic
      regression for categorical variables, and interrater and intrarater reliability
      was assessed by using intraclass correlation coefficients. RESULTS: Compared with
      those in the term-born control group, measurements of brain biparietal diameter,
      corpus callosum, basal ganglia and thalami, and cerebellum were smaller in
      infants in the MLPT group (all P <= .01), while extracerebral space was larger (P
      < .0001). Myelination of the posterior limb of the internal capsule was less
      developed, and gyral maturation was delayed in the MLPT group (both P < .001).
      Signal intensity abnormalities and cysts were uncommon in both groups, with 13
      (6.5%) MLPT infants and one (2%) term infant having abnormalities. Inter- and
      intrarater reliability was good for most measures, with intraclass correlation
      coefficients generally greater than 0.68. CONCLUSION: MLPT birth is associated
      with smaller brain size, less-developed myelination of the posterior limb of the
      internal capsule, and more immature gyral folding than those associated with full
      term birth. These brain changes may form the basis of some of the long-term
      neurodevelopmental deficits observed in MLPT children. Online supplemental
      material is available for this article.

PMID- 24914577
TI  - Characterization of exhaled particles from the human lungs in airway obstruction.
AB  - BACKGROUND: Human breath contains small particles that might be useful for the
      noninvasive diagnosis of lung disease. In this study, the impact of airway
      obstruction on particle emission was investigated. METHODS: Particle number flux
      and particle size distribution were measured for healthy nonsmokers (n=16),
      healthy smokers (n=13), patients with chronic obstructive pulmonary disease
      (n=28, GOLD stage I-IV), and patients with asthma before and after methacholine
      challenge (n=10). The measurements were carried out using a condensation nucleus
      counter (TSI 3760) and a laser spectrometer (PMT LASAIR II-110). RESULTS:
      Particle number per breath showed high intrasubject reproducibility. However,
      there was a large intersubject variability in the number of emitted particles on
      the order of two magnitudes, with no influence of airway obstruction on emission
      level. Methacholine-induced airway obstruction, in subjects with allergic asthma,
      did not change the number of exhaled particles, when compared with prechallenge
      values. For the droplet size distribution averaged per breath, there was no
      difference between healthy subjects and subjects with airway obstruction.
      CONCLUSIONS: Airway obstruction does not change the number flux or size
      distribution of particles in exhaled breath. The high intersubject variability of
      particle emission supports the concept of online determination of aerosol
      properties (primarily number flux, during exhaled breath) during breath
      condensate sampling to properly normalize the results of biochemical analysis. As
      high dilution and variable dilution are the main challenges of biomarker
      assessment in exhaled breath condensate, this normalization procedure would
      significantly add to the value of the technique.

PMID- 24914578
TI  - A Novel Mutation of FOXC1 (R127L) in an Axenfeld-Rieger Syndrome Family with
      Glaucoma and Multiple Congenital Heart Diseases.

PMID- 24914579
TI  - Re: Baker DL et al. Evaluation of two commercial omalizumab/free IgE
      immunoassays: implications of use during therapy. Curr Med Res Opin 2014;30:913
      22.

PMID- 24914580
TI  - Paediatrics: CARPEDIEM--continuous renal replacement therapy for infants.

PMID- 24914581
TI  - Acute kidney injury: Time to get personal with fluid administration and keep
      contrast-induced injury at bay.

PMID- 24914582
TI  - Clinical trials: ISN-ACCTS: global initiatives to improve clinical research.

PMID- 24914584
TI  - Chronic kidney disease: Targeting connexin-43 reduces progression of CKD in mice.

PMID- 24914585
TI  - A cost-effectiveness analysis of celecoxib compared with diclofenac in the
      treatment of pain in osteoarthritis (OA) within the Swedish health system using
      an adaptation of the NICE OA model.
AB  - OBJECTIVES: Celecoxib for the treatment of pain resulting from osteoarthritis
      (OA) was reviewed by the Tandvards- och lakemedelsformansverket-Dental and
      Pharmaceutical Benefits Board (TLV) in Sweden in late 2010. This study aimed to
      evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus a
      proton pump inhibitor (PPI) compared to diclofenac plus a PPI in a Swedish
      setting. METHODS: The National Institute for Health and Care Excellence (NICE) in
      the UK developed a health economic model as part of their 2008 assessment of
      treatments for OA. In this analysis, the model was reconstructed and adapted to a
      Swedish perspective. Drug costs were updated using the TLV database. Adverse
      event costs were calculated using the regional price list of Southern Sweden and
      the standard treatment guidelines from the county council of Stockholm. Costs for
      treating cardiovascular (CV) events were taken from the Swedish DRG codes and the
      literature. RESULTS: Over a patient's lifetime treatment with celecoxib plus a
      PPI was associated with a quality-adjusted life year (QALY) gain of 0.006 per
      patient when compared to diclofenac plus a PPI. There was an increase in
      discounted costs of 529 kr per patient, which resulted in an incremental cost
      effectiveness ratio (ICER) of 82,313 kr ($12,141). Sensitivity analysis showed
      that treatment was more cost effective in patients with an increased risk of
      bleeding or gastrointestinal (GI) complications. CONCLUSIONS: The results suggest
      that celecoxib plus a PPI is a cost effective treatment for OA when compared to
      diclofenac plus a PPI. Treatment is shown to be more cost effective in Sweden for
      patients with a high risk of bleeding or GI complications. It was in this
      population that the TLV gave a positive recommendation. There are known
      limitations on efficacy in the original NICE model.

PMID- 24914586
TI  - Epigenetically regulated microRNAs and their prospect in cancer diagnosis.
AB  - Epigenetic alterations have been reported to deregulate the expression of many
      transcripts, including noncoding RNAs that have no apparent protein-coding
      capacity. Recently, as the result of numerous studies focused on miRNAs, novel
      sequencing technologies have made available the transcription profile of the
      entire human genome. miRNAs as drivers of tumor-suppressive and oncogenic
      functions have been found to be dysregulated in numerous cancer types. However,
      the functions of epigenetically regulated genetic elements other than protein
      coding genes are still a matter of debate. In this review, the authors focus
      mainly on describing the epigenetic regulation of miRNAs in cancer. They also
      discuss the role of miRNAs as potential diagnostic and/or prognostic biomarkers. 

PMID- 24914587
TI  - Computerized respiratory sounds in patients with COPD: a systematic review.
AB  - Computerized respiratory sound analysis provides objective information about the
      respiratory system and may be useful to monitor patients with chronic obstructive
      pulmonary disease (COPD) and detect exacerbations early. For these purposes, a
      thorough understanding of the typical computerized respiratory sounds in patients
      with COPD during stable periods is essential. This review aimed to systematize
      the existing evidence on computerized respiratory sounds in stable COPD. A
      literature search in the Medline, EBSCO, Web of Knowledge and Scopus databases
      was performed. Seven original articles were included. The maximum frequencies of
      normal inspiratory sounds at the posterior chest were between 113 and 130Hz,
      lower than the frequency found at trachea (228 Hz). During inspiration, the
      frequency of normal respiratory sounds was found to be higher than expiration
      (130 vs. 100Hz). Crackles were predominantly inspiratory (2.9-5 vs. expiratory
      0.73-2) and characterized by long durations of the variables initial deflection
      width (1.88-2.1 ms) and two cycle duration (7.7-11.6 ms). Expiratory wheeze rate
      was higher than inspiratory rate. In patients with COPD normal respiratory sounds
      seem to follow the pattern observed in healthy people and adventitious
      respiratory sounds are mainly characterized by inspiratory and coarse crackles
      and expiratory wheezes. Further research with larger samples and following the
      Computerized Respiratory Sound Analysis (CORSA) guidelines are needed.

PMID- 24914583
TI  - Next-generation sequencing for research and diagnostics in kidney disease.
AB  - The advent of next-generation sequencing technologies has enabled genetic
      nephrology research to move beyond single gene analysis to the simultaneous
      investigation of hundreds of genes and entire pathways. These new sequencing
      approaches have been used to identify and characterize causal factors that
      underlie inherited heterogeneous kidney diseases such as nephronophthisis and
      congenital anomalies of the kidney and urinary tract. In this Review, we describe
      the development of next-generation sequencing in basic and clinical research and
      discuss the implementation of this novel technology in routine patient
      management. Widespread use of targeted and nontargeted approaches for gene
      identification in clinical practice will require consistent phenotyping,
      appropriate disease modelling and collaborative efforts to combine and integrate
      data analyses. Next-generation sequencing is an exceptionally promising technique
      that has the potential to improve the management of patients with inherited
      kidney diseases. However, identifying the molecular mechanisms that lead to renal
      developmental disorders and ciliopathies is difficult. A major challenge in the
      near future will be how best to integrate data obtained using next-generation
      sequencing with personalized medicine, including use of high-throughput disease
      modelling as a tool to support the clinical diagnosis of kidney diseases. 

PMID- 24914588
TI  - Nonmarrow hematopoiesis occurs in a hyaluronic-acid-rich node and duct system in
      mice.
AB  - A hyaluronic-acid-rich node and duct system (HAR-NDS) was found on the surface of
      internal organs of mice, and inside their blood and lymph vessels. The nodes (HAR
      Ns) were filled with immune cells of the innate system and were especially
      enriched with mast cells and histiocytes. They also contained hematopoietic
      progenitor cells (HPCs), such as granulocyte-macrophage, erythroid,
      multipotential progenitors, and mast cell progenitors (MCPs). MCPs were the most
      abundant among the HPCs in HAR-Ns. Their frequency was fivefold higher than that
      of the MCPs in bone marrow. In addition, the system contained pluripotent stem
      cells (PSCs) capable of producing CD45(-)Flk1(+) hemangioblast-like cells, which
      subsequently generated various types of HPCs and differentiated blood cells.
      Although HAR-Ns did not appear to harbor enough number of cells capable of long
      term reconstitution or short-term radioprotection of lethally irradiated
      recipients, bone marrow cells were able to engraft in the HAR-NDS and
      reconstitute hematopoietic potentials of the system. PSCs and HPCs were
      consistently found in intravenous, intralymphatic, and intestinal HAR-ND. We
      infer that PSCs and HPCs reside in the HAR-ND and that this novel system may
      serve as an alternative means to traffic immature and mature blood cells
      throughout the body. 

PMID- 24914589
TI  - Lead and cadmium levels in cattle muscle and edible tissues collected from a
      slaughter slab in Nigeria.
AB  - Contamination levels of lead (Pb) and cadmium (Cd) in muscles, liver and kidney
      of 50 randomly selected, freshly slaughtered cattle in Ogun State, Nigeria were
      assessed using an official procedure and atomic absorption spectrophotometry.
      Results showed that Pb and Cd were present in all of the tested samples. Mean Pb
      concentrations were 0.721 +/- 0.180 mg kg(-1), 0.809 +/- 0.220 mg kg(-1) and
      0.908 +/- 0.422 mg kg(-1) in muscle, liver and kidney tissues, respectively. Mean
      Cd concentrations were 0.157 +/- 0.049 mg kg(-1), 0.172 +/- 0.071 mg kg(-1) and
      0.197 +/- 0.070 mg kg(-1) in muscle, liver and kidney tissues, respectively. Pb
      and Cd levels in muscle versus kidney tissues and also in liver versus kidney
      samples were significantly different (p < 0.05). Mean Pb concentrations in all
      tested tissues were significantly higher than the International Standards while
      the mean Cd concentrations in liver and kidney samples were within the limits of
      these standards.

PMID- 24914590
TI  - Monitoring of sulphites levels in shrimps samples collected in Puglia (Italy) by
      ion-exchange chromatography with conductivity detection.
AB  - In shrimps the treatment with sulphiting agents is currently the best option for
      controlling Melanosis, which is a visual defect of the products that compromises
      marketability. However, sulphites may cause pseudo-allergic reactions in humans.
      In this study, 210 samples of shrimps were analysed in order to assess the
      residual levels of sulphiting agents. A quantifiable sulphites concentration was
      detected in 76 samples, and these concentrations were higher than the legal
      limits in eight samples. Considering the important pseudo-allergenic effects
      caused by these food additives, the non-negligible percentage of 3.8% and the
      high levels registered in non-compliant samples (up to 1174.1 mg kg(-1)), a
      strong contrast action based on permanent controls is necessary. Moreover, the
      levels measured in whole samples were up to four times higher than in the edible
      parts. These results suggest to consider the introduction of legal limits,
      related to sulphurous anhydride in the whole product.

PMID- 24914591
TI  - Cadmium, lead and total mercury in Tilapia sp. in Sri Lankan reservoirs.
AB  - In 2010, samples of muscles, liver and gills of Tilapia (Oreochromis sp.) were
      collected from eighteen reservoirs of four districts in Sri Lanka: Anuradapuraya,
      Polonnaruwa (North Central Province), Hambantota (Southern Province) and Ampara
      (Eastern Province). Cd, Pb and Hg were determined using atomic absorption
      spectrometry. Mean Cd, Pb and Hg concentrations in muscle were 0.03 mg/kg, 0.06
      mg/kg and 0.26 mg/kg, respectively, while gills contained 0.02 mg/kg, 0.44 mg/kg
      and 0.36 mg/kg, respectively, on a dry weight basis. The amounts of the three
      metals in liver were 0.30 mg/kg, 2.07 mg/kg and 0.52 mg/kg on a dry weight basis.
      The results revealed that the level of heavy metal concentration in Tilapia does
      not exceed the maximum limit for human consumption according to the European
      Union and Sri Lankan guidelines.

PMID- 24914592
TI  - Aflatoxins in corn and rice sold in Lahore, Pakistan.
AB  - A survey was conducted to evaluate aflatoxin contamination of commonly used food
      in Lahore, Pakistan. In this context, 1125 samples of various food commodities
      were collected from various areas of Lahore city. In corn-based products AFB1 was
      detected in 52% (range 2.0-1405.3 ug kg(-1)) and AFB2 in 25% (range 1.0-55.2 ug
      kg(-1)) of the samples. In super kernel basmati rice, 13.3% of the samples (range
      1.1-32.9 ug kg(-1)) showed the presence of AFB1, 1.9% was contaminated with AFB2
      (range 1.0-8.1 ug kg(-1)) and only one sample exhibited the presence of AFG1. As
      far as the status of basmati rice is concerned, 18.3% was contaminated with AFB1
      (range 1.0-15.4 ug kg(-1)) and 2% was contaminated with AFG1. In 42.9% of
      parboiled rice (range 1.1-9.2 ug kg(-1)) and 36.4% of broken rice (range 2.1-25.3
      ug kg(-1)), samples were contaminated with AFB1.

PMID- 24914593
TI  - A survey on the heavy metal contents in Chinese traditional egg products and
      their potential health risk assessment.
AB  - Pb, Zn and Cu were determined in 35 Preserved Egg (PE) samples, 25 Salted Egg
      (SE) samples and 40 Egg Preserved in Rice Wine (EPRW) samples collected from
      Jiangxi province by ICP-MS. The corresponding health risk for consumers was
      assessed by the target hazard quotients (THQ) and hazard index (HI). Average Pb,
      Zn and Cu content in all samples was 0.125 mg/kg, 10.939 mg/kg and 2.094 mg/kg,
      respectively. Average Pb content in PE was significantly higher than in SE and
      EPRW. THQ and HI values were less than 1, indicating that intake of heavy metals
      from PE, SE and EPRW will not pose a significant hazard risk to humans. However,
      more attention should be paid to control the ingestion by PE, which is the main
      source of Pb, Zn and Cu for consumers among these three egg products.

PMID- 24914594
TI  - Patulin in apple leather in Iran.
AB  - Apple leather is made by dehydration of cooked fruit into leathery sheets. Mould
      growth and patulin production can occur in damaged apples or when fallen fruit is
      collected for apple leather processing. A survey was conducted to determine
      levels and dietary intake of patulin from apple leather marketed in Iran. Patulin
      was detected in all samples at concentrations ranging from <10 to 2559 ug/kg.
      Mean patulin concentration was 620 ug/kg and 91.4% of the samples had levels
      higher than 50 ug/kg. Estimated daily intake (EDI) of patulin for adults and
      children considering the mean concentration of patulin obtained in this study
      (620 ug/kg) were higher than the provisional maximum tolerable daily intake
      (PMTDI) of 0.4 ug/kg bw/day for patulin that has been established by the Joint
      FAO/WHO Expert Committee on Food Additives. This indicated the need for stricter
      control and improvement in processing techniques to reduce the incidence of
      patulin in apple leather.

PMID- 24914595
TI  - Total mercury in canned tuna sold in Canada in 2006.
AB  - Total mercury was measured in 156 composites prepared from 936 samples of canned
      tuna sold in Canada in 2006. Each composite comprised a single brand. Yellowfin
      tuna contained the lowest concentrations, averaging 0.066 mg/kg. Skipjack tuna
      contained slightly higher concentrations, averaging 0.132 mg/kg. The highest
      average concentration was found in the Albacore tuna: mean 0.325 mg/kg, range
      0.174-0.507 mg/kg. The second highest concentration among the 49 albacore
      composites was 0.469 mg/kg. There were 72 composites for which the type of tuna
      was not specified. The mercury in these averaged 0.095 mg/kg and ranged from
      0.016 to 0.237 mg/kg.

PMID- 24914596
TI  - Sodium benzoate and potassium sorbate preservatives in Iranian doogh.
AB  - Sodium benzoate and potassium sorbate are two common preservatives used in Iran,
      yet use of these preservatives in doogh (Iranian dairy-based drink) is forbidden
      according to national standards. The aim of this study was to consider the
      presence of these preservatives in doogh by high-performance liquid
      chromatography with UV detection (HPLC-UV). The method was performed using a C18
      column and detection at 225 nm. The mobile phase contained ammonium acetate
      buffer (pH = 4.2) and acetonitrile (80:20 v/v). The survey included 130 samples
      of doogh for identification and quantification of the named preservatives. All
      samples contained sodium benzoate, but potassium sorbate was detected in only 13%
      of them. The means of benzoate and sorbate were 21.3 +/- 2.7 and 13.3 +/- 39.6 mg
      kg(-1), respectively. The limits of detection were 2 and 40 ng g(-1) for benzoate
      and sorbate, respectively. Results indicate that sodium benzoate may occur in
      doogh naturally.

PMID- 24914597
TI  - Mycological and aflatoxin contamination of peanuts sold at markets in Kinshasa,
      Democratic Republic of Congo, and Pretoria, South Africa.
AB  - Peanut (Arachis hypogaea L.) is an important food crop in sub-Saharan Africa. In
      this survey, the mycological and aflatoxin contamination of peanuts collected
      from Kinshasa, Democratic Republic of Congo, and Pretoria, South Africa, was
      assessed. Twenty peanut samples were purchased randomly at informal markets in
      the two cities and analysed for mycoflora and aflatoxins (AFB1, AFB2, AFG1 and
      AFG2) using standard methods. The results indicated that 95% of the Kinshasa
      samples and 100% of the Pretoria samples were contaminated with aflatoxigenic
      fungi in the ranges 20-49,000 and 40-21,000 CFU/g, respectively. Seventy-five per
      cent of the Kinshasa samples and 35% of the Pretoria samples exceeded the maximum
      limits of AFB1 as set by The Joint FAO/WHO Expert Committee on Food Additives.
      Residents of both cities are at a high risk of aflatoxin exposure despite their
      apparent cultural, socio-economic, geographic and climatic differences. Further
      work needs to be done to understand the supply chains of peanut trade in informal
      markets of the two countries so that interventions are well targeted on a
      regional rather than a national level.

PMID- 24914598
TI  - Heavy metals in produce from urban farms in the San Francisco Bay Area.
AB  - Cadmium (Cd) and lead (Pb) concentrations were analysed in 96 samples of produce
      from seven urban farms, three suburban farms and three grocery stores in the San
      Francisco Bay Area in 2011-2012. Cd concentrations were highest in urban chard
      (0.043 mg kg(-1)) and lowest in urban, suburban and grocery squash (0.003 mg kg(
      1)). Pb concentrations were highest in urban kale (0.080 mg kg(-1)) and lowest in
      grocery squash (0.008 mg kg(-1)). The mean heavy metal concentrations for Cd and
      Pb in all produce types were well below the maximum limits as set by the Food and
      Agriculture Organization (FAO) and the World Health Organization (WHO).
      Individual concentrations of Cd and Pb were below the limits of detection in 26
      of 192 analyses. Cd and Pb concentrations in produce from urban farms were not
      significantly different from produce grown in suburban farms or grocery stores.
      It was concluded that produce from urban community farms in San Francisco, at
      least for the farms studied, is safe for human consumption.

PMID- 24914599
TI  - Aflatoxins, ochratoxins and zearalenone in sorghum and sorghum products in Sudan.
AB  - This survey examined 60 samples of sorghum and 30 samples of sorghum products
      from three states (Khartoum, Kordofan and Gadarif) of Sudan for aflatoxin B1, B2,
      G1 and G2 (AFB1, AFB2, AFG1, AFG2), ochratoxin A and B (OTA, OTB) and zearalenone
      (ZEN), using high performance liquid chromatography with fluorescence detection.
      The limits of detection and limits of quantification were in the range 0.01-0.6
      ug kg(-1) and 0.03-2.0 ug kg(-1), respectively. The frequency of contaminated
      samples with AFB1 from Khartoum, Gadarif and Kordofan state was 38.1%, 22.2% and
      23.8%, respectively. Only two samples of sorghum from Khartoum state were
      contaminated with OTA (3.3%). Concentrations of OTA and OTB were low and may not
      cause problems. No sample of sorghum or sorghum products was contaminated with
      ZEN. Some sorghum samples contained AFB1 concentrations above the European Union
      regulatory limits. The highest contaminated samples were found in Khartoum state.

PMID- 24914600
TI  - Total mercury in milled rice and brown rice from China and health risk
      evaluation.
AB  - Total mercury (THg) levels in 440 pairs of milled rice samples and brown rice
      samples from 15 major rice grain-producing provinces of China were measured and
      the associated health risk via rice consumption for different age categories of
      Chinese population was also assessed. THg contents were measured by a direct
      mercury analyser and the limit of detection (LOD) was 1.5 MUg kg(-1). The THg
      levels for milled rice samples and brown rice samples varied from non-detected to
      17.8 MUg kg(-1) and 1.5 to 25.4 MUg kg(-1), respectively, with a mean level of
      3.4 MUg kg(-1) and 4.9 MUg kg(-1), respectively. The THg levels in all milled and
      brown rice samples were generally low, except three brown rice samples having
      concentrations above the legally set value for cereals (20 MUg kg(-1) Hg). THg
      intakes for different age categories were estimated according to THg content and
      corresponding rice consumption and the associated health risk was evaluated by
      the corresponding provisional tolerable weekly intake (PTWI) for THg (5.0 MUg kg(
      1) bw week(-1)), which was established by the Joint FAO/WHO Expert Committee on
      Food Additives (JECFA). The 50th percentile of the THg intakes via milled rice
      and brown rice consumption for different age categories was in the range 0.09
      0.19 MUg kg(-1) bw week(-1) and 0.14-0.27 MUg kg(-1) bw week(-1), respectively,
      well below the PTWI, suggesting that the associated health risk is relatively
      low. However, the 99.9th percentile of the THg intakes for 2-4-year-old children
      amounted up to 20.6% of the PTWI (milled rice) and 29.5% of the PTWI (brown
      rice), which deserves attention.

PMID- 24914601
TI  - Patulin in apple juices from the Romanian market.
AB  - The aim of this study was to determine patulin levels in apple-based juices from
      the Romanian market and to establish a health risk assessment. For this purpose,
      50 samples of apple-based juices have been purchased from the Romanian market.
      Aliquots were extracted by liquid-liquid extraction using ethyl acetate, analysed
      and quantified using a high-performance liquid chromatography (HPLC) method. The
      patulin level in the apple juices from Romania ranged between <0.7 MUg/l and
      101.9 MUg/l. In 6% of the 50 samples analysed, the maximum limit for patulin as
      set by the European Union (50 MUg/l) was exceeded.

PMID- 24914602
TI  - Fumonisins in corn (Zea mays L.) from Southern Brazil.
AB  - A total of 232 samples of corn commercialised in Santa Catarina state, Southern
      Brazil (temperate zone climate), were evaluated from 2007 to 2012 for fumonisins
      (FBs: FB1 and FB2). Before performing this study, a FBs method with liquid
      chromatography and fluorescence detection (ex. 335; em. 440 nm) was validated
      first. FBs were detected in 46.6% (108 samples), with values ranging from 66 to
      7832 ug kg(-1) for FB1 and 110 to 1201 ug kg(-1) for FB2. The number of
      contaminated corn samples for FB1 and FB2 varied and often presented
      contamination of FB1 only. Per year of analysis, the numbers were: n =
      22/8(FB1/FB2), 44/5(FB1/FB2), 25/12(FB1/FB2), 4(FB1), 6(FB1) and 7(FB1) in 2007,
      2008, 2009, 2010, 2011 and 2012, respectively. The contamination percentage was
      42.3/15.4, 59.5/6.8, 43.8/21.1, 36.4, 35.3 and 33.3%, respectively, during these
      years. Consumers can be exposed to these mycotoxins and their health can be at
      risk through the consumption of contaminated corn.

PMID- 24914603
TI  - Stimulus-dependent modulation of spontaneous low-frequency oscillations in the
      rat visual cortex.
AB  - Research on spontaneous low-frequency oscillations is important to reveal
      underlying regulatory mechanisms in the brain. The mechanism for the stimulus
      modulation of low-frequency oscillations is not known. Here, we used the
      intrinsic optical imaging technique to examine stimulus-modulated low-frequency
      oscillation signals in the rat visual cortex. The stimulation was presented
      monocularly as a flashing light with different frequencies and intensities. The
      phases of low-frequency oscillations in different regions tended to be
      synchronized and the rhythms typically accelerated within a 30-s period after
      stimulation. These phenomena were confined to visual stimuli with specific
      flashing frequencies (12.5-17.5 Hz) and intensities (5-10 mA). The acceleration
      and synchronization induced by the flashing frequency were more marked than those
      induced by the intensity. These results show that spontaneous low-frequency
      oscillations can be modulated by parameter-dependent flashing lights and indicate
      the potential utility of the visual stimulus paradigm in exploring the origin and
      function of low-frequency oscillations.

PMID- 24914604
TI  - Tunable, functional carbon spheres derived from rapid synthesis of resorcinol
      formaldehyde resins.
AB  - In this article, the rapid synthesis of colloidal, spherical polymer resins via
      enhanced copolymerization and polycondensation of resorcinol with formaldehyde is
      presented. The ultrasound-mediated technique assembles perfectly spherical resins
      in less than 5 min due to generated active species and free radicals produced in
      an aqueous ammonia-ethanol-water solvent. In this report, numerous controlled
      experiments account for and support the important role of high intensity
      ultrasounds in the rapid cluster formation, condensation, and gelation process of
      resorcinol with formaldehyde in the presence of ammonia catalyst. After a
      controlled heat treatment process, amorphous carbon spheres are obtained from
      these spherical polymer resins. The effect of temperature (up to 1100  degrees C)
      on the structural evolution of these carbon spheres is meticulously studied which
      is lacking in the previous literature. The resorcinol-formaldehyde resins
      carbonized at 600 and 900  degrees C demonstrate BET surface areas of 592.4
      m(2)/g and 952.5 m(2)/g with specific capacitances of 17.5, and 33.5 F/g (scan
      rate of 5 mV/s), respectively. 

PMID- 24914605
TI  - The effect of dietary carbohydrates in women with polycystic ovary syndrome: a
      systematic review.
AB  - Weight loss improves ovulation, testosterone levels and insulin resistance in
      women with polycystic ovarian syndrome (PCOS), but the optimal diet composition
      is disputed. A diet low in carbohydrates (LCD) may be superior to a standard diet
      in terms of improving fertility, endocrine/metabolic parameters, weight loss and
      satiety in women with PCOS. The aim of the present study was to review the
      literature on the effects of LCD in PCOS, and to summarize the findings into
      evidence-based guidelines. A literature review based on publications in PubMed
      and Cochrane was carried out. The outcomes during LCD were compared to other
      types of diet interventions and exercise. Studies including insulin-sensitizing
      agents, such as metformin, were excluded. The outcomes were fertility,
      endocrine/metabolic parameters, weight loss and satiety. The review resulted in
      fifteen articles. Fertility parameters, endocrine hormones, metabolic outcomes
      and satiety hormones were not further improved during LCD compared to a standard
      diet. LCD had a 1-5% significant additional effect on weight loss compared to a
      standard diet. Energy restriction and weight loss in PCOS improve ovulation
      rates, conception, hyperandrogenemia, glucose- and insulin levels, insulin
      resistance and satiety hormones, whereas diet composition is of less importance.
      A LCD has an additional effect to caloric restriction in terms of weight loss.
      Conclusions are summarized as evidence-based recommendations. 

PMID- 24914606
TI  - Mediastinal staging for lung cancer.
AB  - Staging of the mediastinal and hilar lymph nodes plays a crucial role in
      identifying the best treatment option for patients with confirmed or suspected
      lung cancer and, in many cases, can simultaneously confirm a diagnosis of cancer.
      Noninvasive modalities, such as computed tomography (CT), positron emission
      tomography (PET) and PET-CT, are an important first step in this assessment.
      Ultimately, invasive staging is frequently required to confirm or rule out the
      presence of metastatic disease within the lymph nodes. The present focused review
      describes and compares noninvasive and invasive modalities for mediastinal
      staging in lung cancer. 

PMID- 24914607
TI  - Respiratory clinical trials in Canada--slow, steady progress toward effective,
      evidence-based health care.

PMID- 24914608
TI  - Are we too passive in our attempts to prevent respiratory syncytial virus
      infection in Northern Canada?

PMID- 24914609
TI  - What to do with all of these lung nodules?
AB  - Caplan syndrome is a rare entity that is specific to rheumatoid arthritis and
      presents with multiple, well-defined necrotic nodules in patients with
      occupational dust exposure. The present report describes a case of Caplan
      syndrome involving a 71-year-old man with a known diagnosis of seropositive
      rheumatoid arthritis who presented to the authors' centre with a five-year
      history of multiple, bilateral cavitary lung nodules with mild dyspnea on
      exertion. He was an ex-smoker (30 pack-years) and had previously worked with
      silica. The case highlights the clinical, radiological and pathological features
      of this syndrome and outlines the importance of considering a broad differential
      in the management of pulmonary nodules, especially in patients with rheumatoid
      arthritis. 

PMID- 24914610
TI  - Oxidative carbon-carbon bond cleavage is a key step in spiroacetal biosynthesis
      in the fruit fly Bactrocera cacuminata.
AB  - The early steps of spiroacetal biosynthesis in the fruit fly Bactrocera
      cacuminata (Solanum fly) have been investigated using a series of deuterium
      labeled, oxygenated fatty acid like compounds. These potential spiroacetal
      precursors were administered to male flies, and their volatile emissions were
      analyzed for specific deuterium incorporation by GC/MS. This has allowed the
      order of early oxidative events in the biosynthetic pathway to be determined.
      Together with the already well-established later steps, the results of these in
      vivo investigations have allowed essentially the complete delineation of the
      spiroacetal biosynthetic pathway, beginning from products of primary metabolism.
      A fatty acid equivalent undergoes a series of enzyme-mediated oxidations leading
      to a trioxygenated fatty acid like species that includes a vicinal diol. This
      moiety then undergoes enzyme-mediated oxidative carbon-carbon bond cleavage as
      the key step to generate the C9 unit of the final spiroacetal. This is the first
      time such an oxidative transformation has been reported in insects. A final
      hydroxylation step is followed by spontaneous spiro-cyclization. This distinct
      pathway adds further to the complexity and diversity of biosynthetic pathways to
      spiroacetals. 

PMID- 24914611
TI  - Interfacial engineering of carbon nanofiber-graphene-carbon nanofiber
      heterojunctions in flexible lightweight electromagnetic shielding networks.
AB  - Lightweight carbon materials of effective electromagnetic interference (EMI)
      shielding have attracted increasing interest because of rapid development of
      smart communication devices. To meet the requirement in portable electronic
      devices, flexible shielding materials with ultrathin characteristic have been
      pursued for this purpose. In this work, we demonstrated a facile strategy for
      scalable fabrication of flexible all-carbon networks, where the insulting
      polymeric frames and interfaces have been well eliminated. Microscopically, a
      novel carbon nanofiber-graphene nanosheet-carbon nanofiber (CNF-GN-CNF)
      heterojunction, which plays the dominant role as the interfacial modifier, has
      been observed in the as-fabricated networks. With the presence of CNF-GN-CNF
      heterojunctions, the all-carbon networks exhibit much increased electrical
      properties, resulting in the great enhancement of EMI shielding performance. The
      related mechanism for engineering the CNF interfaces based on the CNF-GN-CNF
      heterojunctions has been discussed. Implication of the results suggests that the
      lightweight all-carbon networks, whose thickness and density are much smaller
      than other graphene/polymer composites, present more promising potential as thin
      shielding materials in flexible portable electronics. 

PMID- 24914613
TI  - Thick growing multilayer nanobrick wall thin films: super gas barrier with very
      few layers.
AB  - Recent work with multilayer nanocoatings composed of polyelectrolytes and clay
      has demonstrated the ability to prepare super gas barrier layers from water that
      rival inorganic CVD-based films (e.g., SiOx). In an effort to reduce the number
      of layers required to achieve a very low oxygen transmission rate (OTR (<0.01
      cc/m(2).day.atm)) in these nanocoatings, buffered cationic chitosan (CH) and
      vermiculite clay (VMT) were deposited using layer-by-layer (LbL) assembly.
      Buffering the chitosan solution and its rinse with 50 mM Trizma base increased
      the thickness of these films by an order of magnitude. The OTR of a 1.6-MUm
      thick, six-bilayer film was 0.009 cc/m(2).day.atm, making this the best gas
      barrier reported for such a small number of layers. This simple modification to
      the LbL process could likely be applied more universally to produce films with
      the desired properties much more quickly. 

PMID- 24914612
TI  - Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric
      modulators of the metabotropic glutamate receptor 5 (mGlu5).
AB  - Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5
      (mGlu5) represent a promising therapeutic strategy for the treatment of
      schizophrenia. Starting from an acetylene-based lead from high throughput
      screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe
      further refinements leading to both dihydronaphthyridinone and
      tetrahydronaphthyridine mGlu5 PAMs containing an alkoxy-based linkage as an
      acetylene replacement. Exploration of several structural features including
      western pyridine ring isomers, positional amides, linker connectivity/position,
      and combinations thereof, reveal that these bicyclic modulators generally exhibit
      steep SAR and within specific subseries display a propensity for pharmacological
      mode switching at mGlu5 as well as antagonist activity at mGlu3. Structure
      activity relationships within a dihydronaphthyridinone subseries uncovered 12c
      (VU0405372), a selective mGlu5 PAM with good in vitro potency, low glutamate fold
      shift, acceptable DMPK properties, and in vivo efficacy in an amphetamine-based
      model of psychosis. 

PMID- 24914614
TI  - Complex interplay among DNA modification, noncoding RNA expression and protein
      coding RNA expression in Salvia miltiorrhiza chloroplast genome.
AB  - Salvia miltiorrhiza is one of the most widely used medicinal plants. As a first
      step to develop a chloroplast-based genetic engineering method for the over
      production of active components from S. miltiorrhiza, we have analyzed the
      genome, transcriptome, and base modifications of the S. miltiorrhiza chloroplast.
      Total genomic DNA and RNA were extracted from fresh leaves and then subjected to
      strand-specific RNA-Seq and Single-Molecule Real-Time (SMRT) sequencing analyses.
      Mapping the RNA-Seq reads to the genome assembly allowed us to determine the
      relative expression levels of 80 protein-coding genes. In addition, we identified
      19 polycistronic transcription units and 136 putative antisense and intergenic
      noncoding RNA (ncRNA) genes. Comparison of the abundance of protein-coding
      transcripts (cRNA) with and without overlapping antisense ncRNAs (asRNA) suggest
      that the presence of asRNA is associated with increased cRNA abundance (p<0.05).
      Using the SMRT Portal software (v1.3.2), 2687 potential DNA modification sites
      and two potential DNA modification motifs were predicted. The two motifs include
      a TATA box-like motif (CPGDMM1, "TATANNNATNA"), and an unknown motif (CPGDMM2
      "WNYANTGAW"). Specifically, 35 of the 97 CPGDMM1 motifs (36.1%) and 91 of the 369
      CPGDMM2 motifs (24.7%) were found to be significantly modified (p<0.01). Analysis
      of genes downstream of the CPGDMM1 motif revealed the significantly increased
      abundance of ncRNA genes that are less than 400 bp away from the significantly
      modified CPGDMM1motif (p<0.01). Taking together, the present study revealed a
      complex interplay among DNA modifications, ncRNA and cRNA expression in
      chloroplast genome. 

PMID- 24914615
TI  - Three-coordinate nickel(II) and nickel(I) thiolate complexes based on the beta
      diketiminate ligand system.
AB  - Mononuclear nickel(II) thiolate complexes [L(tBu)Ni(SEt)] (1) and [L(tBu)Ni(aet)]
      (2, aet = (-)S(CH2)2NH2) (L(tBu) = [HC(C((t)Bu)NC6H3((i)Pr)2)2](-)), supported by
      a bulky nacnac ligand, were synthesized by treatment of the nickel(II) bromide
      precursor [L(tBu)Ni(Br)] (I) with the potassium salts of ethanethiol and
      cysteamine, respectively. The nickel atom in 1 features a planar T-shaped
      environment, while the Ni ion within 2 shows a distorted square planar
      coordination geometry, as the aminoethanethiolate (aet) is coordinated as a
      chelating ligand. In 2 the beta-diketiminate ligand binds in a rarely observed
      kappa(2)C,N coordination mode. Reduction of complex 1 or its benzenethiolate
      analogue [L(tBu)Ni(SPh)] (II) by KC8 resulted in the formation of dinuclear Ni(I)
      thiolates (K.OEt2)(K)[L(tBu)Ni(SEt)]2 (3) and (K.OEt2)2[L(tBu)Ni(SPh)]2 (4),
      respectively. In these compounds [L(tBu)Ni(SR)](-) units are held together by
      potassium cations produced in the reduction process. All compounds mentioned were
      structurally characterized by single-crystal X-ray crystallography. 

PMID- 24914617
TI  - Superhydrophobic nanocomposite surface topography and ice adhesion.
AB  - A method to reduce the surface roughness of a spray-casted
      polyurethane/silica/fluoroacrylic superhydrophobic nanocomposite coating was
      demonstrated. By changing the main slurry carrier fluid, fluoropolymer medium,
      surface pretreatment, and spray parameters, we achieved arithmetic surface
      roughness values of 8.7, 2.7, and 1.6 MUm on three test surfaces. The three
      surfaces displayed superhydrophobic performance with modest variations in
      skewness and kurtosis. The arithmetic roughness level of 1.6 MUm is the smoothest
      superhydrophobic surface yet produced with these spray-based techniques. These
      three nanocomposite surfaces, along with a polished aluminum surface, were
      impacted with a supercooled water spray in icing conditions, and after ice
      accretion occurred, each was subjected to a pressurized tensile test to measure
      ice-adhesion. All three superhydrophobic surfaces showed lower ice adhesion than
      that of the polished aluminum surface. Interestingly, the intermediate roughness
      surface yielded the best performance, which suggests that high kurtosis and
      shorter autocorrelation lengths improve performance. The most ice-phobic
      nanocomposite showed a 60% reduction in ice-adhesion strength when compared to
      polished aluminum. 

PMID- 24914618
TI  - Real-time metabolic analysis of living cancer cells with correlated cellular
      spectro-microscopy.
AB  - In recent years, major efforts have been devoted to the application of microscopy
      with mid-infrared light to the study of living cells and tissue. Despite this
      interest, infrared (IR) microscopy has not realized its full potential in the
      molecular characterization of living systems. This is partly due to the fact that
      current approaches for data mining and analysis of IR absorption spectra have not
      evolved comparably to measurement technology and are not up to the interpretation
      of the complex spectra of living systems such as cells and tissue. In this work
      we show that the use of two-dimensional correlation spectroscopy coupled to IR
      absorption spectro-microscopy allows us to extract the spectral components of
      individual metabolites from time-resolved IR spectra of living cells. We call
      this method correlated cellular spectro-microscopy, and we implement it in the
      study of the glycolytic metabolism of cancer cells. We show that the method can
      detect intermediates of the glycolytic pathway, quantify their rate of formation,
      and correlate this with variations in pH, all in a single measurement. We propose
      the method as a useful tool for the quantitative description of metabolic
      processes in living cells and for the validation of drug candidates aimed at
      suppressing glycolysis in cancer cells. 

PMID- 24914616
TI  - Nanomechanical property maps of breast cancer cells as determined by
      multiharmonic atomic force microscopy reveal Syk-dependent changes in microtubule
      stability mediated by MAP1B.
AB  - The Syk protein-tyrosine kinase, a well-characterized modulator of immune
      recognition receptor signaling, also plays important, but poorly characterized,
      roles in tumor progression, acting as an inhibitor of cellular motility and
      metastasis in highly invasive cancer cells. Multiharmonic atomic force microscopy
      (AFM) was used to map nanomechanical properties of live MDA-MB-231 breast cancer
      cells either lacking or expressing Syk. The expression of Syk dramatically
      altered the cellular topography, reduced cell height, increased elasticity,
      increased viscosity, and allowed visualization of a more substantial microtubule
      network. The microtubules of Syk-expressing cells were more stable to nocodazole
      induced depolymerization and were more highly acetylated than those of Syk
      deficient cells. Silencing of MAP1B, a major substrate for Syk in MDA-MB-231
      cells, attenuated Syk-dependent microtubule stability and reversed much of the
      effect of Syk on cellular topography, stiffness, and viscosity. This study
      illustrates the use of multiharmonic AFM both to quantitatively map the local
      nanomechanical properties of living cells and to identify the underlying
      mechanisms by which these properties are modulated by signal transduction
      machinery. 

PMID- 24914619
TI  - Unraveling the processing and activation of snake venom metalloproteinases.
AB  - Snake venom metalloproteinases (SVMPs) are zinc-dependent enzymes responsible for
      most symptoms of human envenoming. Like matrix metalloproteinases (MMPs) and a
      disintegrin and metalloproteinase (ADAM) proteins, SVMPs are synthesized as
      zymogens, and enzyme activation is regulated by hydrolysis of their prodomain,
      but the processing of SVMPs is still unclear. In this study, we attempted to
      identify the presence of prodomain in different compartments of snake venom
      glands as zymogens or in the free form to elucidate some mechanism involved in
      SVMP activation. Using antibodies obtained by immunization with a recombinant
      prodomain, bands of zymogen molecular mass and prodomain peptides were detected
      mostly in gland extracts all along the venom production cycle and in the venom
      collected from the lumen at the peak of venom production. Prodomain was detected
      in secretory cells mostly in the secretory vesicles near the Golgi. We
      hypothesize that the processing of SVMPs starts within secretory vesicles and
      continues in the lumen of the venom gland just after enzyme secretion and
      involves different steps compared to ADAMs and MMPs but can be used as a model
      for studying the relevance of peptides resulting from prodomain processing and
      degradation for controlling the activity of metalloproteinases. 

PMID- 24914620
TI  - Investigations on the effect of O(6)-benzylguanine on the formation of dG-dC
      interstrand cross-links induced by chloroethylnitrosoureas in human glioma cells
      using stable isotope dilution high-performance liquid chromatography electrospray
      ionization tandem mass spectrometry.
AB  - Chloroethylnitrosoureas (CENUs) are bifunctional alkylating agents widely used
      for the clinical treatment of cancer. They exert anticancer activity by inducing
      DNA interstrand cross-links (ICLs) within GC base pairs to form dG-dC cross
      links. This lesion inhibits DNA double strand separation during replication and
      transcription and results in the apoptosis of cancer cells. However, O(6)
      alkylguanine DNA alkyltransferase (AGT) repairs the DNA ICLs by removing the
      alkyl group at the O(6) position of either O(6)-(2-chloroethyl)deoxyguanosine
      (O(6)-ClEtdGuo) or N1,O(6)-ethanodeoxyguanosine (N1,O(6)-EtdGuo), which are
      intermediates in the formation of dG-dC cross-links. The action of AGT leads to
      drug resistance against CENUs. O(6)-Benzylguanine (O(6)-BG) was identified as an
      effective AGT inhibitor that enhances the antitumor effects of CENUs. In this
      study, the effect of O(6)-BG on the formation of dG-dC cross-links was
      investigated by treating human brain glioma SF767 cells with 1-[(4-amino-2-methyl
      5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea (ACNU). The levels of dG-dC
      cross-link were determined using stable isotope dilution high-performance liquid
      chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS).
      The results indicated that ACNU induced higher levels of dG-dC cross-link in
      SF767 cells pretreated with O(6)-BG compared to cells without O(6)-BG
      pretreatment. The highest dG-dC cross-linking levels were generally observed at
      12 h for all drug concentration groups, a result which was consistent with
      cytotoxicity assay. These results provided direct evidence for the enhancement of
      dG-dC cross-linking levels caused by the inhibition of AGT by O(6)-BG. These data
      indicate that dG-dC cross-links may be developed as a biomarker for evaluating
      the activity of novel O(6)-BG analogues as AGT inhibitors for combination therapy
      with CENUs. 

PMID- 24914621
TI  - A new synthetic approach to 6-unsubstituted phenanthridine and phenanthridine
      like compounds under mild and metal-free conditions.
AB  - A new and mild synthetic approach for the synthesis of 6-unsubstituted
      phenanthridine and phenanthridine-like compounds under metal-free conditions at
      room temperature has been developed. The strategy involved a tandem azide
      rearrangement/intramolecular annulation and oxidation reactions of biarylmethyl
      azide precursors to obtain the desired products in up to 99% yields with high
      regioselectivity. 

PMID- 24914622
TI  - Label-free multimodal protease detection based on protein/perylene dye coassembly
      and enzyme-triggered disassembly.
AB  - The development of novel assays for protease sensing plays an important role in
      clinical diagnostics and therapeutics. Herein, we report a supramolecular
      platform for label-free protease detection, based on protein/dye self-assembly
      and enzyme-triggered disassembly. In a typical case, coassembly of protamine
      sulfate and perylene dye via electrostatic attractions and pi-pi interactions
      caused significant colorimetric and fluorescent responses. Subsequent addition of
      trypsin was found to cleave the amide bonds of protein, triggering the
      dissociation of protein/dye aggregates and the release of perylene dyes. The
      enzyme-triggered disassembly was transduced into multiple readouts including
      absorption, fluorescence, and polarization, which were exploited for trypsin
      detection and inhibitor testing. This assay was also used for turn-on
      fluorescence detection of cathepsin B, an enzyme known to be overexpressed in
      mammalian cancer cells. The integration of supramolecular self-assembly into
      enzyme detection in this work has provided a novel label-free biosensing platform
      which is highly sensitive with multimodal readouts. The relative simplicity of
      the approach avoids the need for time-consuming substrate synthesis, and is also
      amenable to naked eye detection. 

PMID- 24914623
TI  - [Lights and darks of a picture. The life of Giovanni Francesco Barbieri, "il
      Guercino"--the Squinter].

PMID- 24914624
TI  - [The influence of printing technology conditions on the accuracy and
      reproducibility of printed contrast panels for assessing contrast sensitivity].
AB  - PURPOSE: Contrast studies can provide important knowledge for treatment decisions
      before surgery or for assessing the driving ability of professional drivers.
      Accordingly, high demands are placed on contrast panels to obtain reliable and
      reproducible results. The aim of the study is to find out if the contrast panels
      on the market meet the requirements. METHODS: On the basis of measurement
      evaluation and schematic presentations potential sources of error can be
      identified. These sources of error may have a decisive influence on the
      assessment of contrast vision. RESULTS: Far-reaching analyses have shown that
      three parameters can have a significant influence on the accuracy and
      reproducibility of printed contrast panels. This holds for certain properties of
      the printing substrate, the type of representation of display element, and the
      choice of the colourant. Only the correct interaction between the substrate and
      the print colour effects an angle-independent contrast. A matt substrate is
      necessary, which has a low difference to the printed contrast element in respect
      of glow, so that possible angle differences have no influence on the contrast
      assessment. The contrast elements of a contrast panel vary in brightness.
      Conventional methods for typographical representation of different brightnesses
      use the method of screening. This causes undesirable edges, which weaken in
      particular the lower-contrast elements unintentionally. Use of special colours
      can avoid this effect. In the visible wavelength range the studied contrast
      elements have an irregular absorption behaviour. Because of differences between
      the lighting surroundings, this can lead to a differentiated stimulation of cones
      in practice. Appropriate colourants have a constant absorption behaviour.
      CONCLUSION: To get representative results of contrast studies the production of
      contrast panels needs more knowledge about the interaction between paper and
      colour than is typically required for print products. On the basis of a prototype
      optimisation, approaches are presented in this article.

PMID- 24914625
TI  - Developmental trajectories of anxious and depressive problems during the
      transition from childhood to adolescence: personality * parenting interactions.
AB  - This study examined separate developmental trajectories of anxious and depressive
      symptoms from childhood to adolescence (9-15 years) in a community-based sample
      (N = 290). At three measurement points, mothers and fathers reported on their
      children's anxious and depressive symptoms, and at Time 1 they reported on lower
      order child personality facets and on their parenting. By means of growth mixture
      modeling, three developmental trajectories were identified for anxious symptoms:
      steady low (82%), moderate increasing-decreasing (5.9%), and high declining
      groups (12.1%). For depressive symptoms, two developmental trajectories were
      found: steady low (94.1%) and moderate increasing groups (5.9%). Higher shyness,
      irritability, and altruism predicted membership in more problematic anxious and
      depressive groups. The personality facets energy, optimism, compliance, and
      anxiety were unique predictors for class membership for anxious symptoms, and the
      effects of shyness, irritability, and compliance were moderated by overreactive
      parenting. Shyness and irritability increased the probability of following the
      moderate increasing-decreasing anxiety trajectory, but only in the context of
      high or average levels of overreactive parenting. Compliance increased the
      probability of following the moderate increasing-decreasing and high decreasing
      trajectories in the context of high overreactive parenting. Our results indicate
      that childhood personality facets differentiate trajectories of anxious and
      depressive symptoms in theoretically compelling ways. 

PMID- 24914626
TI  - Protein mixtures of environmentally friendly zein to understand protein-protein
      interactions through biomaterials synthesis, hemolysis, and their antimicrobial
      activities.
AB  - Industrially important zein protein has been employed to understand its
      interactions with two model proteins bovine serum albumin (BSA) and cytochrome c
      (Cyc,c) following the in vitro synthesis of Au NPs so as to expand its
      applicability for biological applications. Interactions were studied under the
      effect of temperature variation by UV-visible and fluorescence emission studies.
      Temperature induced unfolding in the protein mixtures indicated their degree of
      mutual interactions through simultaneous nucleation of gold nanoparticles (Au
      NPs) and their subsequent shape control effects. Zein + BSA mixtures showed
      favorable protein-protein interactions over the entire mole fraction range with
      maximum close to x(BSA) = 0.24, whereas zein + Cyc,c showed such interactions
      only in the zein rich region with significant demixing in the Cyc,c rich region
      of the mixtures. Both hydrophobic as well as hydrophilic domains in the unfolded
      states were driving such interactions in the case of zein + BSA mixtures while
      demixing was the result of the predominant hydrophilic nature of Cyc,c and its
      self-aggregation behavior in the Cyc,c rich region in contrast to the predominant
      hydrophobic nature of zein. Zein + BSA mixtures produced small roughly spherical
      Au NPs fully coated with protein, whereas the demixing zone of zein + Cyc,c
      mixtures generated highly anisotropic NPs with little protein coating. To explore
      their biological applications, protein conjugated NPs of both mixtures were
      subjected to hemolysis where NPs coated with the former mixture showed little
      hemolysis and may act as drug delivery vehicles in systemic circulation in
      comparison to the latter. Both kinds of NPs further demonstrated their
      extraordinary antimicrobial activities with different kinds of strains and proved
      to be highly important environmentally friendly biomaterials.

PMID- 24914627
TI  - Accuracy of continuous noninvasive hemoglobin monitoring: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Noninvasive hemoglobin (Hb) monitoring devices are available in the
      clinical setting, but their accuracy and precision against central laboratory Hb
      measurements have not been evaluated in a systematic review and meta-analysis.
      METHODS: We conducted a comprehensive search of the literature (2005 to August
      2013) with PubMed, Web of Science and the Cochrane Library, reviewed references
      of retrieved articles, and contacted manufactures to identify studies assessing
      the accuracy of noninvasive Hb monitoring against central laboratory Hb
      measurements. Two independent reviewers assessed the quality of studies using
      recommendations for reporting guidelines and quality criteria for method
      comparison studies. Pooled mean difference and standard deviation (SD) (95%
      limits of agreement) across studies were calculated using the random-effects
      model. Heterogeneity was assessed using the I statistic. RESULTS: A total of 32
      studies (4425 subjects, median sample size of 44, ranged from 10 to 569 patients
      per study) were included in this meta-analysis. The overall pooled random-effects
      mean difference (noninvasive-central laboratory) and SD were 0.10 +/- 1.37 g/dL (
      2.59 to 2.80 g/dL, I = 95.9% for mean difference and 95.0% for SD). In subgroup
      analysis, pooled mean difference and SD were 0.39 +/- 1.32 g/dL (-2.21 to 2.98
      g/dL, I = 93.0%, 71.4%) in 13 studies conducted in the perioperative setting and
      were -0.51 +/- 1.59 g/dL (-3.63 to 2.62 g/dL, I = 83.7%, 96.4%) in 5 studies
      performed in the intensive care unit setting. CONCLUSIONS: Although the mean
      difference between noninvasive Hb and central laboratory measurements was small,
      the wide limits of agreement mean clinicians should be cautious when making
      clinical decisions based on these devices.

PMID- 24914628
TI  - Cognitive outcome after spinal anesthesia and surgery during infancy.
AB  - BACKGROUND: Observational studies on pediatric anesthesia neurotoxicity have been
      unable to distinguish long-term effects of general anesthesia (GA) from factors
      associated with the need for surgery. A recent study on elementary school
      children who had received a single GA during the first year of life demonstrated
      an association in otherwise healthy children between the duration of anesthesia
      and diminished test scores and also revealed a subgroup of children with "very
      poor academic achievement" (VPAA), scoring below the fifth percentile on
      standardized testing. Analysis of postoperative cognitive function in a similar
      cohort of children anesthetized with an alternative to GA may help to begin to
      separate the effects of anesthesia from other confounders. METHODS: We used a
      novel methodology to construct a combined medical and educational database to
      search for these effects in a similar cohort of children receiving spinal
      anesthesia (SA) for the same procedures. We compared former patients with a
      control population of students matched by grade, gender, year of testing, and
      socioeconomic status. RESULTS: Vermont Department of Education records were
      analyzed for 265 students who had a single exposure to SA during infancy for
      circumcision, pyloromyotomy, or inguinal hernia repair. Exposure to SA and
      surgery had no significant effect on the odds of children having VPAA.
      (mathematics: P = 0.18; odds ratio 1.50, confidence interval (CI), 0.83-2.68;
      reading: P = 0.55; odds ratio = 1.19, CI, 0.67-2.1). There was no relationship
      between duration of exposure to SA and surgery and performance on mathematics (P
      = 0.73) or reading (P = 0.57) standardized testing. There was a small but
      statistically significant decrease in reading and math scores in the exposed
      group (mathematics: P = 0.03; reading: P = 0.02). CONCLUSIONS: We found no link
      between duration of surgery with infant SA and scores on academic achievement
      testing in elementary school. We also found no relationship between infant SA and
      surgery with VPAA on elementary school testing, although the CIs were wide.

PMID- 24914629
TI  - Novel use of perineural pregabalin infusion for analgesia in a rat neuropathic
      pain model.
AB  - BACKGROUND: The anticonvulsant drugs pregabalin and gabapentin are often used
      systemically to treat some forms of chronic neuropathic pain. However, many
      patients report side effects serious enough to cause discontinuation of the drug.
      Here we present evidence that pregabalin may block neuropathic pain when applied
      to the site of nerve injury in a rat neuropathic pain model. METHODS: Forty male
      Sprague Dawley rats were randomized into 4 groups: sciatic nerve crush injury
      with perineural pregabalin treatment (treatment), crush injury with perineural
      saline treatment (saline control), crush injury with subcutaneous pregabalin
      treatment (systemic drug control), and sham surgery (sham surgery control).
      Animals received either continuous infusions of 1% pregabalin for 7 days
      (treatment and systemic control) or saline (saline control) and were tested for
      pain behaviors using incapacitance meter, guarding scores, and radiant heat
      withdrawal latency (Hargreaves method). Nerves were studied using histology and
      immunohistochemistry for alpha(2)delta-1 receptors thought to mediate the central
      analgesic action of pregabalin. RESULTS: Treatment rats had significantly better
      guarding scores than systemic drug controls or saline controls (P < 0.0001) and
      had significantly better incapacitance scores than systemic drug controls and
      saline controls (P <= 0.001). Hargreaves method data showed hypoalgesia in all
      injured animals with no difference among injured groups (P = 0.80).
      Qualitatively, immunohistochemistry likely showed equivalent expression of the
      alpha(2)delta-1 calcium channel at the injured nerve site in all nerve-injured
      animals. CONCLUSIONS: Perineural pregabalin administration produced superior
      analgesia compared with that of systemic pregabalin in this neuropathic pain
      model. Perineural pregabalin treatment may provide a useful alternative to
      systemic pregabalin treatment for neuropathic pain.

PMID- 24914630
TI  - Effect of local anesthetic dilution on the onset time and duration of double
      injection sciatic nerve block: a prospective, randomized, blinded evaluation.
AB  - BACKGROUND: Among the various factors influencing the success rate, onset time,
      and duration of peripheral nerve blocks, the role of local anesthetics
      concentration remains uncertain. In this prospective, randomized, single-blinded
      study, we evaluated whether varying the dilution of a fixed dose of mepivacaine
      solution influenced onset time and duration of sciatic nerve block. METHODS:
      Ninety ASA physical status I to II patients scheduled for foot surgery were
      randomly allocated to receive a double-injection Labat sciatic nerve block with
      12 mL mepivacaine 2% (group concentration I = 45 patients) or 24 mL of
      mepivacaine 1% (group volume II = 45 patients). The nerve stimulator was
      initially set at 2 Hz, 0.1 millisecond, 1 mA. The total amount of local
      anesthetic (240 mg) was kept constant and equally divided between the peroneal
      and tibial nerves. All patients also received an ultrasound-guided popliteal
      sciatic nerve catheter for postoperative analgesia. Times to readiness for
      surgery, performance, and offset of local anesthetic were recorded. Our primary
      end point was to determine a possible difference in offset time between groups.
      Continuous variables were expressed as median (IQR) and compared with the
      Wilcoxon-Mann-Whitney U test; WMWodds are reported together with their 95%
      confidence interval. RESULTS: The overall success rate of sciatic nerve block was
      99%. Time of performance was shorter in group I, 120 seconds (90-150 seconds),
      than that in group II, 150 seconds (120-180 seconds) (P = 0.0048; WMWodds 2.26
      [1.35-4.34]). The onset time of sensory and motor sciatic nerve block was 4
      minutes (2-9 minutes) in group I and 6 minutes (4-10 minutes) in group II (P =
      0.41; WMWodds 1.21 [0.77-1.95]), while the duration of sensory block was 235
      minutes (203-250 minutes) in group I, and 240 minutes (218-247 minutes) in group
      II respectively (P = 0.51; WMWodds 1.20 [0.69-2.16]). CONCLUSIONS: We found no
      evidence that varying volume and concentration while maintaining a fixed total
      dose of mepivacaine alters the onset time and duration of double-injection
      sciatic nerve block. Considering our WMWodds results, possible differences in
      onset time and duration comparable to differences in the performance time between
      groups cannot be excluded.

PMID- 24914631
TI  - The benefits and challenges of robotic-assisted hysterectomy.
AB  - PURPOSE OF REVIEW: To analyze the recent evidence on robotic hysterectomy while
      highlighting its benefits and challenges. RECENT FINDINGS: Increased rates of
      robotic hysterectomy have led to decreasing rates of abdominal hysterectomy,
      after rates of the latter approach have been stagnant for many years. Robotic
      surgery has also the possible advantage of a relatively short learning curve,
      even though the case number required to reach proficiency may be actually closer
      to 100 cases. Recent studies comparing robotic and laparoscopic hysterectomy for
      benign indications have not demonstrated a clear advantage for either approach in
      terms of complications, blood loss, and hospital stay. The higher cost of robotic
      hysterectomy remains a significant disadvantage of this surgical approach,
      although the total cost may decrease with increasing surgeon's experience (via
      shorter operative time) and may be offset in some circumstances by reduced
      hospital stay and cost of complications compared with abdominal hysterectomy.
      SUMMARY: The place of robotic hysterectomy in the gynecologic surgical
      armamentarium is still evolving. Although recent studies highlight the
      comparative outcomes of robotic and laparoscopic hysterectomy for benign cases,
      most surgeons are unlikely to be equally proficient in both techniques. Future
      studies will need to question whether subgroups of patients with complex benign
      disease such as endometriosis and pelvic adhesive disease may benefit from the
      robotic assistance.

PMID- 24914632
TI  - Inertial microfluidic physics.
AB  - Microfluidics has experienced massive growth in the past two decades, and
      especially with advances in rapid prototyping researchers have explored a
      multitude of channel structures, fluid and particle mixtures, and integration
      with electrical and optical systems towards solving problems in healthcare,
      biological and chemical analysis, materials synthesis, and other emerging areas
      that can benefit from the scale, automation, or the unique physics of these
      systems. Inertial microfluidics, which relies on the unconventional use of fluid
      inertia in microfluidic platforms, is one of the emerging fields that make use of
      unique physical phenomena that are accessible in microscale patterned channels.
      Channel shapes that focus, concentrate, order, separate, transfer, and mix
      particles and fluids have been demonstrated, however physical underpinnings
      guiding these channel designs have been limited and much of the development has
      been based on experimentally-derived intuition. Here we aim to provide a deeper
      understanding of mechanisms and underlying physics in these systems which can
      lead to more effective and reliable designs with less iteration. To place the
      inertial effects into context we also discuss related fluid-induced forces
      present in particulate flows including forces due to non-Newtonian fluids,
      particle asymmetry, and particle deformability. We then highlight the inverse
      situation and describe the effect of the suspended particles acting on the fluid
      in a channel flow. Finally, we discuss the importance of structured channels,
      i.e. channels with boundary conditions that vary in the streamwise direction, and
      their potential as a means to achieve unprecedented three-dimensional control
      over fluid and particles in microchannels. Ultimately, we hope that an improved
      fundamental and quantitative understanding of inertial fluid dynamic effects can
      lead to unprecedented capabilities to program fluid and particle flow towards
      automation of biomedicine, materials synthesis, and chemical process control. 

PMID- 24914634
TI  - Religion and the rainbow struggle: does religion factor into attitudes toward
      homosexuality and same-sex civil unions in Brazil?
AB  - The provision of civil liberties to LGBT persons has become part of a global
      movement in societies across the world. In Brazil, a recent judicial ruling for
      the first time established the right for homosexual couples to enter into civil
      unions, despite the presence of widespread disapproval of homosexuality among the
      population and opposition from prominent religious groups. Picking up on this
      issue, the following study examines whether religion may factor into the
      attitudes Brazilians hold toward homosexuality and same-sex civil unions. Using
      data from the Brazilian Social Research Survey, we find that the most restrictive
      views toward homosexuality and the strongest opposition to same-sex civil unions
      are most prevalent among devoted followers of historical Protestant, Pentecostal,
      and Catholic faith traditions, whereas adherents of Afro-Brazilian and spiritist
      religions, as well as those with no religious commitment, are inclined to assume
      a more tolerant moral posture toward such issues. The findings point to religion
      as a potential influence in future public policy initiatives and social movements
      involving LGBT issues in Brazil. 

PMID- 24914635
TI  - Impaired regulator of G protein signaling 2 transcription facilitates vascular
      remodeling in injured rat aorta.
AB  - BACKGROUND: The activation of Gq-protein-coupled receptors induces proliferation
      of vascular smooth muscle cells (VSMCs) proliferation and is involved in vascular
      remodeling. The regulator of G protein signaling 2 (RGS2), which accelerates the
      termination of Gq protein signaling, may play a role in vascular remodeling.
      However, this role remains unclear. METHODS: Aortic balloon injury or sham
      operation was produced in male Wistar rats. Histological examination and gene
      expression analysis were performed after surgery. In cultured VSMCs after
      modulation of RGS2 expression, cell proliferation was also evaluated. RESULTS: At
      day 3 after injury, RGS2 transcription was reduced by 52.8% (P <0.05 vs. sham
      group) with vascular remodeling. In cultured VSMCs stimulated by endothelin-1,
      phenylephrine or angiotensin II, the proliferation of RGS2 overexpressed cells
      was significantly inhibited; the proliferation of RGS2 downregulated cells was
      significantly promoted, compared with that of RGS2 normal cells. Moreover, after
      incubation with angiotensin II of high concentration (>10 MUmol/l) or long term
      (>8 h), the RGS2 expression was clearly downregulated in cultured VSMCs.
      Administration of an angiotensin receptor blocker, valsartan (20 mg/kg per day)
      starting from 1 week preballoon injury to 3 days after injury, restored aortic
      RGS2 transcription and improved vascular remodeling. CONCLUSION: These results
      suggested that the inhibiting effect of RGS2 on VSMC proliferation is
      downregulated in vascular remodeling of injured rat aorta, and this effect is
      likely to be mediated by angiotensin II signaling.

PMID- 24914636
TI  - An early literary description of emotional syncope in the Fifth Canto of Dante
      Alighieri's Commedia: 'E caddi come corpo morto cade'.
AB  - Dante's Divine Comedy is universally acclaimed as one of the great masterpieces
      in world literature. It is written in first person singular and this gives an
      intimate acquaintance with the vision of the poet. In the Fifth Canto, he
      exquisitely describes the story of Paolo Malatesta and Francesca da Rimini,
      illicit lovers killed by Francesca's husband, Gianciotto Malatesta. The story,
      dramatically told by Francesca, deeply moves the poet, who suddenly faints. In
      the words of Dante himself: 'E caddi come corpo morto cade' (And fell, even as a
      dead body falls). This probably is the first literary description of an emotional
      syncope in world literature. We found that three great plastic artists (John
      Flaxman, William Blake and Gustave Dore) captured the crucial moment of the
      syncope in three extraordinary images left for posterity. 

PMID- 24914637
TI  - A novel tunnel Na(0.61)Ti(0.48)Mn(0.52)O2 cathode material for sodium-ion
      batteries.
AB  - A novel tunnel Na(0.61)Ti(0.48)Mn(0.52)O2 material is explored as a cathode for
      sodium-ion batteries for the first time. It can deliver a reversible discharge
      capacity of 86 mA h g(-1) with an average voltage of 2.9 V at 0.2 C rate in a
      sodium half cell, exhibiting good rate capability and capacity retention at a cut
      off voltage of 1.5-4 V. These results indicate that tunnel
      Na(0.61)Ti(0.48)Mn(0.52)O2 has a great potential application in large scale
      energy storage.

PMID- 24914638
TI  - Short communication: HIV-1 gag genetic variation in a single acutely infected
      participant defined by high-resolution deep sequencing.
AB  - Acute HIV-1 infection is characterized by the rapid generation of highly diverse
      genetic variants to adapt to the new host environment. Understanding the dynamics
      of viral genetic variation at this stage of infection is critical for vaccine
      design efforts and early drug treatment. Here, using a high-resolution deep
      sequencing approach targeting the HIV-1 gag region, we reveal very early immune
      pressure with dramatic subpopulation shifts in a single acutely infected
      participant providing further insight into the genetic dynamics of acute HIV-1
      infection.

PMID- 24914639
TI  - Attitude and impact of perceived depression in the workplace.
AB  - Information concerning the occurrence and consequences of depression in the
      workplace is scarce. This study estimates how workers perceive depression, to
      investigate depression-related disabilities, and management of depression in the
      workplace. This investigation is based on a cross-sectional web-based survey of
      1,000 workers recruited from online sources. The participants were Brazilian
      workers, aged 16-64 years, current workers and managers, or who have worked
      within the past year. Subjects answered a 13-item questionnaire about depression,
      its related consequences in the workplace, and available resources to handle
      depression. Common symptoms attributable to depression were crying, loss of
      interest, and sadness. Almost one in five participants reported having ever been
      labeled by a doctor/medical professional as suffering from depression. However,
      the majority of ever-depressed workers (73.5%) remained working. Performance
      related impairments were reported by around 60% of depressed workers who
      continued working. Over half of them also complained about cognitive symptoms
      (concentration difficulties, indecisiveness, forgetfulness). One in three workers
      had taken off work due to depression (mean 65.7 out-of-role days), with these
      periods being lengthier for men than women. Managers underestimated the number of
      days out-of-role (29.5 days). The findings suggested that identification and
      management of symptoms of depression should be set as a priority in worker's
      health care. 

PMID- 24914640
TI  - Importance-satisfaction analysis for primary care physicians' perspective on EHRs
      in Taiwan.
AB  - The Taiwan government has been promoting Electronic Health Records (EHRs) to
      primary care physicians. How to extend EHRs adoption rate by measuring
      physicians' perspective of importance and performance of EHRs has become one of
      the critical issues for healthcare organizations. We conducted a comprehensive
      survey in 2010 in which a total of 1034 questionnaires which were distributed to
      primary care physicians. The project was sponsored by the Department of Health to
      accelerate the adoption of EHRs. 556 valid responses were analyzed resulting in a
      valid response rate of 53.77%. The data were analyzed based on a data-centered
      analytical framework (5-point Likert scale). The mean of importance and
      satisfaction of four dimensions were 4.16, 3.44 (installation and maintenance),
      4.12, 3.51 (product effectiveness), 4.10, 3.31 (system function) and 4.34, 3.70
      (customer service) respectively. This study provided a direction to government by
      focusing on attributes which physicians found important but were dissatisfied
      with, to close the gap between actual and expected performance of the EHRs. The
      authorities should emphasize the potential advantages in meaningful use and
      provide training programs, conferences, technical assistance and incentives to
      enhance the national level implementation of EHRs for primary physicians. 

PMID- 24914641
TI  - Narratives of natural recovery: youth experience of social inclusion through
      green care.
AB  - The aim of this study has been to investigate the effects of Green Care services
      for youth in vulnerable situations risking social exclusion. Green Care
      enterprises represent alternative arenas in which people can work with animals,
      agriculture and other tasks related to nature. We interviewed nine persons, aged
      17-27, working in three different places, two or more times over a two-year
      period. We looked at essential beneficial factors in order to better understand
      how the "green" element could add to more traditional recovery factors. We found
      that the youth described core success factors corresponding to well-known
      recovery factors such as recognition, supportive relationships, motivation,
      meaning, positive coping, self-esteem, confidence and hope. The effective factors
      can be described as: (a) The leader's ability to create a good group atmosphere,
      (b) the varied tasks which allow step-wise increases in self-efficacy, and (c)
      experiences with animals and in nature that provide comfort for youth who lack
      trust in people and need safe situations to recover a positive sense of self. We
      followed a process in which several persons gradually regained self-respect and
      the motivation for further education or a job outside the Green Care enterprise.
      The study illustrates that Green Care can be an important supplement in helping
      people back to a satisfying life and meaningful roles in society. 

PMID- 24914642
TI  - Tinggianthura alba: a new genus and species of Anthuridae (Isopoda, Cymothoida,
      Anthuroidea) from Pulau Tinggi, Johor, Malaysia with an updated key to the genera
      of Anthuridae.
AB  - A new anthurid isopod from dead coral rubble and stones in the intertidal area of
      Pulau Tinggi, Johor, Malaysia, is described. It is placed in a new genus and
      species, Tinggianthura alba. Tinggianthura is characterized by: (1) subtriangular
      carpus shape of pereopods 4-7, (2) pereopod 1 propodus palm without prominent
      tooth or steps and (3) maxillipedal palp 2-articled. 

PMID- 24914643
TI  - How robust is the optimistic update bias for estimating self-risk and population
      base rates?
AB  - Humans hold unrealistically optimistic predictions of what their future holds.
      These predictions are generated and maintained as people update their beliefs
      more readily when receiving information that calls for adjustment in an
      optimistic direction relative to information that calls for adjustment in a
      pessimistic direction. Thus far this update bias has been shown when people make
      estimations regarding the self. Here, we examine whether asymmetric belief
      updating also exists when making estimations regarding population base rates. We
      reveal that while participants update beliefs regarding risk in the population in
      an asymmetric manner, such valence-dependent updating of base rates can be
      accounted for by priors. In contrast, we show that optimistic updating regarding
      the self is a robust phenomenon, which holds even under different empirical
      definitions of desirable information. 

PMID- 24914645
TI  - Raising awareness of scoliosis.

PMID- 24914646
TI  - Call for better service integration to help improve child health.

PMID- 24914647
TI  - UK has highest risk of premature infant mortality in Europe.

PMID- 24914648
TI  - More training and education can reduce asthma deaths.

PMID- 24914649
TI  - Staff urged to consider how cancer therapy affects teens.

PMID- 24914650
TI  - Charity urges review of crematoria practices on dealing with baby ashes.

PMID- 24914652
TI  - Warwickshire community nurses win Nursing Standard award.

PMID- 24914653
TI  - Nurses list tackling obesity as a major health challenge.

PMID- 24914658
TI  - Research essentials: how to develop effective networks to support evidence-based
      practice.

PMID- 24914659
TI  - Fathers' emotional work deserves more attention from health professionals: the
      conflicted emotional response of fathers to the pre-term birth if their child is
      significant even though the men may not express it openly.

PMID- 24914665
TI  - Leeds cardiac care article reported review findings out of context.

PMID- 24914666
TI  - Student voice - making mistakes is part of the learning process.

PMID- 24914667
TI  - Multidisciplinary meetings as an effective clinical intervention.
AB  - When used well, multidisciplinary meetings can function in the same way as other
      clinical interventions to improve communication, efficiency and outcomes. They
      help break down barriers, manage difficult emotions, and benefit service users
      and staff. But it is imperative that they are well prepared, well attended, and
      that the purpose and agenda are agreed. It is also vital to have an efficient
      chair and that meetings take place in an environment where feelings can be shared
      openly and respected. Services should recognise and address relevant training and
      support requirements. 

PMID- 24914668
TI  - Giving hope to families in palliative care and implications for practice.
AB  - Caring for a dying child and the family is one of the greatest nursing
      challenges. The way in which care is delivered will shape the experience they are
      about to face. Hope plays a crucial role in helping people cope, and healthcare
      professionals can foster appropriate hopes ethically, while maintaining open and
      honest communication. If palliative care is discussed with clients and families
      from the time of diagnosis, they can face realistic decisions better and not feel
      that they are 'giving up'. They need to know that everything possible is being
      done to improve the quality of the time left to them. 

PMID- 24914669
TI  - What it means to be the parent of a child with a disability or complex health
      need.
AB  - AIM: To explore how parents of children with disabilities and complex health
      needs make sense of the circumstances in which they find themselves. METHOD: A
      series of in-depth semi-structured interviews were undertaken with the parents of
      34 children (from 33 families) with a disability or a complex health need. The
      families were nominated by health professionals to one of three study subgroups:
      children with a disability, children with a life-limiting or life-threatening
      illness, or children with technology dependence. Interviews were recorded and
      transcribed. FINDINGS: Analysis of parents' responses related to sense-making
      revealed two main categories: 'diagnosis' and 'personal, cultural and personality
      factors'. These two categories alongside the two other main study themes,
      'impact' and 'need for help and support' reported in the previous two articles in
      this series - linked into a final study theme: 'battleground'. CONCLUSION: For
      the parents of children with complex health needs and disabilities, the sense
      that they make of their situation plays a pivotal role in determining how parents
      experience the impact of disability and the need for help and support.

PMID- 24914670
TI  - Raising awareness of scoliosis among children's nurses.
AB  - Scoliosis affects up to 3% of adolescents, some babies and young children, and
      many children with existing neuromuscular and syndromic conditions. It is the
      most common spinal deformity. Not all children with scoliosis require active
      intervention, but for more significant, progressive curves, bracing and/or
      surgery may be required. Bracing studies have historically been of low
      methodological quality, but a recent randomised controlled trial ( Weinstein et
      al 2013 ) has shown the efficacy of bracing in decreasing curve progression, thus
      reducing the necessity of surgery for some patients. Modern surgical techniques
      are effective in correcting scoliosis, but the surgery is major, with significant
      risks. Early identification of scoliosis is vital to maximise effective
      treatment, support the child and family, and optimise holistic health. 

PMID- 24914671
TI  - High seroprevalence of human herpesviruses in HIV-infected individuals attending
      primary healthcare facilities in rural South Africa.
AB  - Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan
      Africa. These are important to provide an indication of potential burden of HHV
      related disease, in particular in human immunodeficiency virus (HIV)-infected
      individuals who are known to be at increased risk of these conditions in the
      Western world. In this cross-sectional study among 405 HIV-infected and
      antiretroviral therapy naive individuals in rural South Africa the seroprevalence
      of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type
      2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein
      Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with
      VZV seropositivity were low educational status and having children. Lack of in
      house access to drinking water was independently associated with positive HSV-1
      serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity.
      Increasing age was associated with higher IgG titres to both EBV and CMV, whereas
      CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover,
      IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively
      correlated. The high HHV seroprevalence emphasises the importance of awareness of
      these viral infections in HIV-infected individuals in South Africa. 

PMID- 24914672
TI  - Worries about being judged versus being harmed: disentangling the association of
      social anxiety and paranoia with schizotypy.
AB  - Paranoia is a dimension of clinical and subclinical experiences in which others
      are believed to have harmful intentions. Mild paranoid concerns are relatively
      common in the general population, and more clinically severe paranoia shares
      features with social anxiety and is a key characteristic of schizotypy. Given
      that subclinical manifestations of schizotypy and paranoia may predict the
      occurrence of more severe symptoms, disentangling the associations of these
      related constructs may advance our understanding of their etiology; however no
      known studies to date have comprehensively evaluated how paranoia relates to
      social anxiety and schizotypy. The current research sought to examine the
      association of paranoia, assessed across a broad continuum of severity, with 1)
      the positive and negative schizotypy dimensions and 2) social anxiety.
      Specifically, the study tested a series of six competing, a priori models using
      confirmatory factor analysis in a sample of 862 young adults. As hypothesized,
      the data supported a four-factor model including positive schizotypy, negative
      schizotypy, social anxiety, and paranoia factors, suggesting that these are
      distinct constructs with differing patterns of interrelationships. Paranoia had a
      strong association with positive schizotypy, a moderate association with social
      anxiety, and a minimal association with negative schizotypy. The results are
      consistent with paranoia being part of a multidimensional model of schizotypy and
      schizophrenia. Prior studies treating schizotypy and schizophrenia as homogenous
      constructs often produce equivocal or non-replicable results because these
      dimensions are associated with distinct etiologies, presentations, and treatment
      responses; thus, the present conceptualization of paranoia within a
      multidimensional schizotypy framework should advance our understanding of these
      constructs. 

PMID- 24914673
TI  - Stress Analysis on Single Cobalt/Chrome Prosthesis With a 15-mm Cantilever Placed
      Over 10/13/15-mm-length Implants: A Simulated Photoelastic Model Study.
AB  - The aim of study was to assess the stress around 10/13/15-mm implants in the
      mandibular area with a 15-mm cantilevered acrylic-resin-coated prostheses
      following the application force, using the photoelasticity method. Three
      photoelastic mandibular models were created containing 10-, 13-, and 15-mm
      implants in length and 3.75 mm in diameter. The implants had bore internal hex
      connections and were placed parallel to the intermental region. Abutments with 1
      mm high cuffs were placed over the implants, and a single cobalt/chrome metallic
      prosthesis with a 15-mm cantilever, coated with thermoplastic acrylic resin, was
      placed on top. Loads of 1.0 and 3.0 bars were applied, and the images were
      photographed and assessed by photoelasticity method. The greatest stress levels
      were observed for the 10-mm implants. The stress pattern was the same regardless
      of implant length; only the magnitude of the stress along the implant body
      revealed changes. Increased implant length played a role in reducing stress on
      the investigated area of the model, and the 15-mm implants exhibited the best
      performance in regard to stress distribution. The highest stress levels were
      found in the implants closest to the cantilever and the central implant. The
      longest implants were more favorable in regard to the stress distribution on the
      peri-implant support structures in the 15-mm cantilevered prosthesis under loads.

PMID- 24914675
TI  - Measurements of droplet size distribution and analysis of nasal spray atomization
      from different actuation pressure.
AB  - BACKGROUND: To evaluate the deposition efficiency of spray droplets in a nasal
      cavity produced from a spray device, it is important to determine droplet size
      distribution, velocity, and its dispersion during atomization. Due to the
      limiting geometric dimensions of the nasal cavity airway, the spray plume cannot
      develop to its full size inside the nasal vestibule to penetrate the nasal valve
      region for effective drug deposition. METHODS: Particle/droplet image analysis
      was used to determine local mean droplet sizes at eight regions within the spray
      plume under different actuation pressures that represent typical hand operation
      from pediatric to adult patients. RESULTS: The results showed that higher
      actuation pressure produces smaller droplets in the atomization. Stronger
      actuation pressure typical of adult users produces a longer period of the fully
      atomized spray stage, despite a shorter overall spray duration. This produces
      finer droplets when compared with the data obtained by weaker actuation pressure,
      typical of pediatric users. CONCLUSION: The experimental technique presented is
      able to capture a more complete representation of the droplet size distribution
      and the atomization process during an actuation. The measured droplet size
      distribution produced can be related to the empirically defined deposition
      efficiency curve of the nasal cavity, allowing a prediction of the likely
      deposition.

PMID- 24914674
TI  - Configuring a powered knee and ankle prosthesis for transfemoral amputees within
      five specific ambulation modes.
AB  - Lower limb prostheses that can generate net positive mechanical work may restore
      more ambulation modes to amputees. However, configuration of these devices
      imposes an additional burden on clinicians relative to conventional prostheses;
      devices for transfemoral amputees that require configuration of both a knee and
      an ankle joint are especially challenging. In this paper, we present an approach
      to configuring such powered devices. We developed modified intrinsic control
      strategies--which mimic the behavior of biological joints, depend on
      instantaneous loads within the prosthesis, or set impedance based on values from
      previous states, as well as a set of starting configuration parameters. We
      developed tables that include a list of desired clinical gait kinematics and the
      parameter modifications necessary to alter them. Our approach was implemented for
      a powered knee and ankle prosthesis in five ambulation modes (level-ground
      walking, ramp ascent/descent, and stair ascent/descent). The strategies and set
      of starting configuration parameters were developed using data from three
      individuals with unilateral transfemoral amputations who had previous experience
      using the device; this approach was then tested on three novice unilateral
      transfemoral amputees. Only 17% of the total number of parameters (i.e., 24 of
      the 140) had to be independently adjusted for each novice user to achieve all
      five ambulation modes and the initial accommodation period (i.e., time to
      configure the device for all modes) was reduced by 56%, to 5 hours or less. This
      approach and subsequent reduction in configuration time may help translate
      powered prostheses into a viable clinical option where amputees can more quickly
      appreciate the benefits such devices can provide.

PMID- 24914676
TI  - Cell position during larval development affects postdiapause development in
      Megachile rotundata (Hymenoptera: Megachilidae).
AB  - Megachile rotundata (F.) (Hymenoptera: Megachilidae) is the primary pollinator of
      alfalfa in the northwestern United States and western Canada and provides
      pollination services for onion, carrot, hybrid canola, various legumes, and other
      specialty crops. M. rotundata females are gregarious, nest in cavities either
      naturally occurring or in artificial nesting blocks, where they construct a
      linear series of brood cells. Because of the physical layout of the nest, the age
      of the larvae within the nest and the microenvironment the individual larvae
      experience will vary. These interacting factors along with other maternal inputs
      affect the resulting phenotypes of the nest mates. To further our understanding
      of in-nest physiology, gender and developmental rates were examined in
      relationship to cell position within the nest. Eighty-two percent of the females
      were located within the first three cells, those furthest from the nest entrance.
      For those individuals developing in cells located in the deepest half of the
      nest, the sex of the previous bee had a significant effect on the female decision
      of the gender of the following nest mate. Removing the prepupae from the nest and
      rearing them under identical conditions demonstrated that position within the
      nest during larval development had a significant effect on the postdiapause
      developmental rates, with males whose larval development occurred deeper in the
      nest developing more slowly than those toward the entrance. No positional effect
      on postdiapause developmental rates was noted for the females. The cell position
      effect on male postdiapause developmental rate demonstrates that postdiapause
      development is not a rigid physiological mechanism uniform in all individuals,
      but is a dynamic plastic process shaped by past environmental conditions. 

PMID- 24914678
TI  - ForceAtlas2, a continuous graph layout algorithm for handy network visualization
      designed for the Gephi software.
AB  - Gephi is a network visualization software used in various disciplines (social
      network analysis, biology, genomics...). One of its key features is the ability
      to display the spatialization process, aiming at transforming the network into a
      map, and ForceAtlas2 is its default layout algorithm. The latter is developed by
      the Gephi team as an all-around solution to Gephi users' typical networks (scale
      free, 10 to 10,000 nodes). We present here for the first time its functioning and
      settings. ForceAtlas2 is a force-directed layout close to other algorithms used
      for network spatialization. We do not claim a theoretical advance but an attempt
      to integrate different techniques such as the Barnes Hut simulation, degree
      dependent repulsive force, and local and global adaptive temperatures. It is
      designed for the Gephi user experience (it is a continuous algorithm), and we
      explain which constraints it implies. The algorithm benefits from much feedback
      and is developed in order to provide many possibilities through its settings. We
      lay out its complete functioning for the users who need a precise understanding
      of its behaviour, from the formulas to graphic illustration of the result. We
      propose a benchmark for our compromise between performance and quality. We also
      explain why we integrated its various features and discuss our design choices.

PMID- 24914677
TI  - Comparing the effects of symbiotic algae (Symbiodinium) clades C1 and D on early
      growth stages of Acropora tenuis.
AB  - Reef-building corals switch endosymbiotic algae of the genus Symbiodinium during
      their early growth stages and during bleaching events. Clade C Symbiodinium algae
      are dominant in corals, although other clades - including A and D - have also
      been commonly detected in juvenile Acroporid corals. Previous studies have been
      reported that only molecular data of Symbiodinium clade were identified within
      field corals. In this study, we inoculated aposymbiotic juvenile polyps with
      cultures of clades C1 and D Symbiodinium algae, and investigated the different
      effect of these two clades of Symbiodinium on juvenile polyps. Our results showed
      that clade C1 algae did not grow, while clade D algae grew rapidly during the
      first 2 months after inoculation. Polyps associated with clade C1 algae exhibited
      bright green fluorescence across the body and tentacles after inoculation. The
      growth rate of polyp skeletons was lower in polyps associated with clade C1 algae
      than those associated with clade D algae. On the other hand, antioxidant activity
      (catalase) of corals was not significantly different between corals with clade C1
      and clade D algae. Our results suggested that clade D Symbiodinium algae easily
      form symbiotic relationships with corals and that these algae could contribute to
      coral growth in early symbiosis stages. 

PMID- 24914679
TI  - Astrocytic Toll-like receptor 3 is associated with ischemic preconditioning
      induced protection against brain ischemia in rodents.
AB  - BACKGROUND: Cerebral ischemic preconditioning (IPC) protects brain against
      ischemic injury. Activation of Toll-like receptor 3 (TLR3) signaling can induce
      neuroprotective mediators, but whether astrocytic TLR3 signaling is involved in
      IPC-induced ischemic tolerance is not known. METHODS: IPC was modeled in mice
      with three brief episodes of bilateral carotid occlusion. In vitro, IPC was
      modeled in astrocytes by 1-h oxygen-glucose deprivation (OGD). Injury and
      components of the TLR3 signaling pathway were measured after a subsequent
      protracted ischemic event. A neutralizing antibody against TLR3 was used to
      evaluate the role of TLR3 signaling in ischemic tolerance. RESULTS: IPC in vivo
      reduced brain damage from permanent middle cerebral artery occlusion in mice and
      increased expression of TLR3 in cortical astrocytes. IPC also reduced damage in
      isolated astrocytes after 12-h OGD. In astrocytes, IPC or 12-h OGD alone
      increased TLR3 expression, and 12-h OGD alone increased expression of
      phosphorylated NFkappaB (pNFkappaB). However, IPC or 12-h OGD alone did not alter
      the expression of Toll/interleukin receptor domain-containing adaptor-inducing
      IFNbeta (TRIF) or phosphorylated interferon regulatory factor 3 (pIRF3). Exposure
      to IPC before OGD increased TRIF and pIRF3 expression but decreased pNFkappaB
      expression. Analysis of cytokines showed that 12-h OGD alone increased IFNbeta
      and IL-6 secretion; 12-h OGD preceded by IPC further increased IFNbeta secretion
      but decreased IL-6 secretion. Preconditioning with TLR3 ligand Poly I:C increased
      pIRF3 expression and protected astrocytes against ischemic injury; however, cells
      treated with a neutralizing antibody against TLR3 lacked the IPC- and Poly I:C
      induced ischemic protection and augmentation of IFNbeta. CONCLUSIONS: The results
      suggest that IPC-induced ischemic tolerance is mediated by astrocytic TLR3
      signaling. This reprogramming of TLR3 signaling by IPC in astrocytes may play an
      important role in suppression of the post-ischemic inflammatory response and
      thereby protect against ischemic damage. The mechanism may be via activation of
      the TLR3/TRIF/IRF3 signaling pathway.

PMID- 24914680
TI  - Cdc25 and the importance of G2 control: insights from developmental biology.
AB  - While cell proliferation is an essential part of embryonic development, cells
      within an embryo cannot proliferate freely. Instead, they must balance
      proliferation and other cellular events such as differentiation and morphogenesis
      throughout embryonic growth. Although the G1 phase has been a major focus of
      study in cell cycle control, it is becoming increasingly clear that G2 regulation
      also plays an essential role during embryonic development. Here we discuss the
      role of Cdc25, a key regulator of mitotic entry, with a focus on several recent
      examples that show how the precise control of Cdc25 activity and the G2/M
      transition are critical for different aspects of embryogenesis. We finish by
      discussing a promising technology that allows easy visualization of embryonic and
      adult cells potentially regulated at mitotic entry, permitting the rapid
      identification of other instances where the exit from G2 plays an essential role
      in development and tissue homeostasis.

PMID- 24914681
TI  - Efficacy of a crosslinked hyaluronic acid-based hydrogel as a tear film
      supplement: a masked controlled study.
AB  - Keratoconjunctivitis sicca (KCS), or dry eye, is a significant medical problem in
      both humans and dogs. Treating KCS often requires the daily application of more
      than one type of eye drop in order to both stimulate tear prodcution and provide
      a tear supplement to increase hydration and lubrication. A previous study
      demonstrated the potential for a crosslinked hyaluronic acid-based hydrogel
      (xCMHA-S) to reduce the clinical signs associated with KCS in dogs while using a
      reduced dosing regimen of only twice-daily administration. The present study
      extended those results by comparing the use of the xCMHA-S to a standard HA
      containing tear supplement in a masked, randomized clinical study in dogs with a
      clinical diagnosis of KCS. The xCMHA-S was found to significantly improve ocular
      surface health (conjunctival hyperaemia, ocular irritation, and ocular discharge)
      to a greater degree than the alternative tear supplement (P = 0.0003). Further,
      owners reported the xCMHA-S treatment as being more highly effective than the
      alternative tear supplement (P = 0.0024). These results further demonstrate the
      efficacy of the xCMHA-S in reducing the clinical signs associated with KCS,
      thereby improving patient health and owner happiness. 

PMID- 24914682
TI  - Is theta burst stimulation applied to visual cortex able to modulate peripheral
      visual acuity?
AB  - Repetitive transcranial magnetic stimulation is usually applied to visual cortex
      to explore the effects on cortical excitability. Most researchers therefore
      concentrate on changes of phosphene threshold, rarely on consequences for visual
      performance. Thus, we investigated peripheral visual acuity in the four quadrants
      of the visual field using Landolt C optotypes before and after repetitive
      stimulation of the visual cortex. We applied continuous and intermittend theta
      burst stimulation with various stimulation intensities (60%, 80%, 100%, 120% of
      individual phosphene threshold) as well as monophasic and biphasic 1 Hz
      stimulation, respectively. As an important result, no serious adverse effects
      were observed. In particular, no seizure was induced, even with theta burst
      stimulation applied with 120% of individual phosphene threshold. In only one case
      stimulation was ceased because the subject reported intolerable pain. Baseline
      visual acuity decreased over sessions, indicating a continuous training effect.
      Unexpectedly, none of the applied transcranial magnetic stimulation protocols had
      an effect on performance: no change in visual acuity was found in any of the four
      quadrants of the visual field. Binocular viewing as well as the use of peripheral
      instead of foveal presentation of the stimuli might have contributed to this
      result. Furthermore, intraindividual variability could have masked the TMS-
      induced effects on visual acuity. 

PMID- 24914684
TI  - X chromosome-linked CNVs in male infertility: discovery of overall duplication
      load and recurrent, patient-specific gains with potential clinical relevance.
AB  - INTRODUCTION: Spermatogenesis is a highly complex process involving several
      thousand genes, only a minority of which have been studied in infertile men. In a
      previous study, we identified a number of Copy Number Variants (CNVs) by high
      resolution array-Comparative Genomic Hybridization (a-CGH) analysis of the X
      chromosome, including 16 patient-specific X chromosome-linked gains. Of these,
      five gains (DUP1A, DUP5, DUP20, DUP26 and DUP40) were selected for further
      analysis to evaluate their clinical significance. MATERIALS AND METHODS: The copy
      number state of the five selected loci was analyzed by quantitative-PCR on a
      total of 276 idiopathic infertile patients and 327 controls in a conventional
      case-control setting (199 subjects belonged to the previous a-CGH study). For one
      interesting locus (intersecting DUP1A) additional 338 subjects were analyzed.
      RESULTS AND DISCUSSION: All gains were confirmed as patient-specific and the
      difference in duplication load between patients and controls is significant (p =
      1.65 * 10(-4)). Two of the CNVs are private variants, whereas 3 are found
      recurrently in patients and none of the controls. These CNVs include, or are in
      close proximity to, genes with testis-specific expression. DUP1A, mapping to the
      PAR1, is found at the highest frequency (1.4%) that was significantly different
      from controls (0%) (p = 0.047 after Bonferroni correction). Two mechanisms are
      proposed by which DUP1A may cause spermatogenic failure: i) by affecting the
      correct regulation of a gene with potential role in spermatogenesis; ii) by
      disturbing recombination between PAR1 regions during meiosis. This study allowed
      the identification of novel spermatogenesis candidate genes linked to the 5 CNVs
      and the discovery of the first recurrent, X-linked gain with potential clinical
      relevance.

PMID- 24914683
TI  - Adenosine prevents TNFalpha-induced decrease in endothelial mitochondrial mass
      via activation of eNOS-PGC-1alpha regulatory axis.
AB  - We tested whether adenosine, a cytoprotective mediator and trigger of
      preconditioning, could protect endothelial cells from inflammation-induced
      deficits in mitochondrial biogenesis and function. We examined this question
      using human microvascular endothelial cells exposed to TNFalpha. TNFalpha
      produced time and dose-dependent decreases in mitochondrial membrane potential,
      cellular ATP levels, and mitochondrial mass, preceding an increase in apoptosis.
      These effects were prevented by co-incubation with adenosine, a nitric oxide (NO)
      donor, a guanylate cyclase (GC) activator, or a cell-permeant cyclic GMP (cGMP)
      analog. The effects of adenosine were blocked by a nitric oxide synthase
      inhibitor, a soluble guanylate cyclase inhibitor, a morpholino antisense
      oligonucleotide to endothelial nitric oxide synthase (eNOS), or siRNA knockdown
      of the transcriptional coactivator, PGC-1alpha. Incubation with exogenous NO, a
      GC activator, or a cGMP analog reversed the effect of eNOS knockdown, while the
      effect of NO was blocked by inhibition of GC. The protective effects of NO and
      cGMP analog were prevented by siRNA to PGC-1alpha. TNFalpha also decreased
      expression of eNOS, cellular NO levels, and PGC-1alpha expression, which were
      reversed by adenosine. Exogenous NO, but not adenosine, rescued expression of PGC
      1alpha in cells in which eNOS expression was knocked down by eNOS antisense
      treatment. Thus, TNFalpha elicits decreases in endothelial mitochondrial function
      and mass, and an increase in apoptosis. These effects were reversed by adenosine,
      an effect mediated by eNOS-synthesized NO, acting via soluble guanylate
      cyclase/cGMP to activate a mitochondrial biogenesis regulatory program under the
      control of PGC-1alpha. These results support the existence of an adenosine
      triggered, mito-and cytoprotective mechanism dependent upon an eNOS-PGC-1alpha
      regulatory pathway, which acts to preserve endothelial mitochondrial function and
      mass during inflammatory challenge. 

PMID- 24914685
TI  - Hypoxia-inducible factor-2alpha is an essential catabolic regulator of
      inflammatory rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disorder that manifests as
      chronic inflammation and joint tissue destruction. However, the etiology and
      pathogenesis of RA have not been fully elucidated. Here, we explored the role of
      the hypoxia-inducible factors (HIFs), HIF-1alpha (encoded by HIF1A) and HIF
      2alpha (encoded by EPAS1). HIF-2alpha was markedly up-regulated in the intimal
      lining of RA synovium, whereas HIF-1alpha was detected in a few cells in the
      sublining and deep layer of RA synovium. Overexpression of HIF-2alpha in joint
      tissues caused an RA-like phenotype, whereas HIF-1alpha did not affect joint
      architecture. Moreover, a HIF-2alpha deficiency in mice blunted the development
      of experimental RA. HIF-2alpha was expressed mainly in fibroblast-like
      synoviocytes (FLS) of RA synovium and regulated their proliferation, expression
      of RANKL (receptor activator of nuclear factor-kappaB ligand) and various
      catabolic factors, and osteoclastogenic potential. Moreover, HIF-2alpha-dependent
      up-regulation of interleukin (IL)-6 in FLS stimulated differentiation of TH17
      cells-crucial effectors of RA pathogenesis. Additionally, in the absence of IL-6
      (Il6-/- mice), overexpression of HIF-2alpha in joint tissues did not cause an RA
      phenotype. Thus, our results collectively suggest that HIF-2alpha plays a pivotal
      role in the pathogenesis of RA by regulating FLS functions, independent of HIF
      1alpha.

PMID- 24914686
TI  - Molecular evolution of candidate genes for crop-related traits in sunflower
      (Helianthus annuus L.).
AB  - Evolutionary analyses aimed at detecting the molecular signature of selection
      during crop domestication and/or improvement can be used to identify genes or
      genomic regions of likely agronomic importance. Here, we describe the DNA
      sequence-based characterization of a pool of candidate genes for crop-related
      traits in sunflower. These genes, which were identified based on homology to
      genes of known effect in other study systems, were initially sequenced from a
      panel of improved lines. All genes that exhibited a paucity of sequence
      diversity, consistent with the possible effects of selection during the evolution
      of cultivated sunflower, were then sequenced from a panel of wild sunflower
      accessions an outgroup. These data enabled formal tests for the effects of
      selection in shaping sequence diversity at these loci. When selection was
      detected, we further sequenced these genes from a panel of primitive landraces,
      thereby allowing us to investigate the likely timing of selection (i.e.,
      domestication vs. improvement). We ultimately identified seven genes that
      exhibited the signature of positive selection during either domestication or
      improvement. Genetic mapping of a subset of these genes revealed co-localization
      between candidates for genes involved in the determination of flowering time,
      seed germination, plant growth/development, and branching and QTL that were
      previously identified for these traits in cultivated * wild sunflower mapping
      populations. 

PMID- 24914687
TI  - Frequency of the apolipoprotein E epsilon4 allele in a memory clinic cohort in
      Beijing: a naturalistic descriptive study.
AB  - OBJECTIVES: To describe the distribution of apolipoprotein E (APOE) genotypes
      among an elderly Chinese patient population with memory complaints treated in a
      memory clinic in Beijing and to compare the epsilon4 allele frequency among
      individuals with subjective cognitive impairment (SCI), mild cognitive impairment
      (MCI) and Alzheimer's disease (AD). METHODS: A total of 385 subjects with memory
      complaints participated in the study, including 216 patients with AD, 56 with
      MCI, 17 with SCI, and 96 with other types of cognitive impairment. A total of 75
      healthy elderly control subjects were also recruited. The polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used
      to investigate the APOE genotypes. RESULTS: The frequency of the epsilon4 allele
      was 19.6 percent for the entire sample of patients who had memory complaints. The
      APOE allele distribution differed between women and men (22.6% and 14.9%,
      respectively; p<0.05) in the individuals with memory complaints. Compared with
      the control group (7.3%), the prevalence of the APOE epsilon4 allele was
      significantly higher in the AD (23.6%) and MCI (21.4%) groups and was slightly
      increased in the SCI (14.7%) group. CONCLUSIONS: In the memory clinic, we
      observed a higher prevalence of the APOE epsilon4 allele among Chinese AD and MCI
      patients. A similar trend was observed in patients with SCI. These findings
      suggest that nondemented APOE epsilon4 allele carriers with memory complaints may
      have a greater genetic risk for AD and should be monitored more closely.

PMID- 24914688
TI  - The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in
      pregnant women.
AB  - Many pregnant Muslim women fast during Ramadan. Leptin has an important role in
      the reproductive system and hormones. In this study, FSH, LH, oestrogen,
      progesterone and leptin were measured in the first, second and fourth week of
      Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were
      analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change
      during the study. A significant change in FSH, oestrogen, progesterone and leptin
      was observed (p < 0.05). The lowest value of FSH was in the second week of
      Ramadan. Progesterone increased at the end of Ramadan and the second week after.
      Oestrogen increased significantly during Ramadan and decreased after Ramadan. A
      decreasing trend was seen in LH during the Ramadan and 2 weeks after (p < 0.1).
      Leptin decreased significantly 2 weeks after Ramadan. We found poor weight gain
      and hypoleptinaemia in pregnant fasted women during the study. Food restriction
      in pregnant fasted women during Ramadan may induce poor weight gain during
      pregnancy. These data confirm that Ramadan fasting by pregnant women may have
      potential risks during pregnancy. We recommend further study to evaluate long
      term effects of Ramadan fasting during pregnancy in different countries with
      different food habits and traditions, to obtain reliable and documented data.

PMID- 24914690
TI  - Restrictive Strabismus and Diplopia 2 Years After
      Conjunctivodacryocystorhinostomy With Medpor-Coated Tear Drain.
AB  - A 19-year-old woman who underwent conjunctivodacryocystorhinostomy with Medpor
      Coated Tear Drain 2 years ago presented with diplopia on left gaze for 4 months.
      Limitation of extraocular movement of OS on left gaze was observed on duction
      test. The forced duction test revealed restriction of the left medial rectus
      muscle. Orbital MRI demonstrated an enhancing soft tissue lesion surrounding the
      tube in inferomedial aspect of left orbit. Removal of the tube and adhesiolysis
      were performed. Histologic findings were consistent with a chronic inflammation
      with fibrosis. After surgery, limitation of extraocular movement and diplopia
      were completely resolved. Jones tube coated with a thin layer of porous
      polyethylene allows the ingrowth of fibrovascular tissue into the coating,
      decreasing the probability of tube extrusion, but can also accelerate fibrotic
      changes around the tube causing restrictive strabismus. 

PMID- 24914691
TI  - Immune cells in the melanoma microenvironment hold information for prediction of
      the risk of recurrence and response to treatment.
AB  - Melanoma is an immunogenic tumor and immunotherapy treatment has established an
      increase in disease-free and overall survival in melanoma patients. However, a
      complex network of immunosuppressive mechanisms has been demonstrated to occur at
      the tumor site and in locoregional immune districts, such as sentinel lymph nodes
      (SLNs). The interplay between tumor cells and the local microenvironment leads to
      a tumor-driven shaping of the immune response that results in a heterogeneous
      cellular and molecular composition of tumor infiltrating lymphocytes (TILs).
      Several studies have reported the potential prognostic value of TILs infiltrating
      primary tumors and the association of 'immune signature' in SLNs and in melanoma
      metastases with prognosis and responsiveness to immunotherapeutic approaches.
      However, a systematic and deeper characterization of the local immunological
      status of TILs and SLNs is still required to refine melanoma stage
      classification. 

PMID- 24914689
TI  - Impact of ketamine on learning and memory function, neuronal apoptosis and its
      potential association with miR-214 and PTEN in adolescent rats.
AB  - Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a
      general pediatric anesthetic and anti-depressive drug. Recent studies suggest
      that ketamine enhances neuronal apoptosis in developing rats. The goal of this
      study is to explore whether ketamine could result in learning and memory
      impairment and neurodegeneration in adolescent rats, and if so, whether the
      effects of ketamine are associated with miR-214 and PTEN expression. Fifty-day
      old SD rats were randomly divided into three groups receiving ketamine at 30, or
      80 mg/kg, i.p. or saline for seven consecutive days. Twenty-four hours after the
      last treatment, learning and memory function were tested by the Morris water
      maze. The rats were then decapitated, and the brains were isolated for detection
      of neuronal apoptosis and protein PTEN expression by TUNEL and
      immunohistochemistry respectively. Expression levels of the miR-214 and PTEN in
      the hippocampus were measured by qRT-PCR and western blot analysis respectively.
      Ketamine administered to the adolescent rats at a dose of 80 mg/kg rather than
      the lower dose of 30 mg/kg caused learning and memory impairment, increased the
      number of apoptotic cells in the hippocampal CA1 region, cerebral cortex and
      subcortical region, decreased the miR-214 levels and increased PTEN protein
      expression in hippocampus. The results suggest that ketamine at a dose of 80
      mg/kg in the adolescent rats is able to induce the learning and memory impairment
      and neurodegeneration, in which the down-regulation of miR-214 and high
      expression of PTEN protein may be involved. 

PMID- 24914692
TI  - Endothelial cells direct mesenchymal stem cells toward a smooth muscle cell fate.
AB  - Under defined conditions, mesenchymal stem cells can differentiate into unique
      cell types, making them attractive candidates for cell-based disease therapies.
      Ischemic diseases would greatly benefit from treatments that include the
      formation of new blood vessels from mesenchymal stem cells. However, blood
      vessels are complex structures composed of endothelial cells and smooth muscle
      cells, and their assembly and function in a diseased environment is reliant upon
      joining with the pre-existing vasculature. Although endothelial cell/smooth
      muscle cell interactions are well known, how endothelial cells may influence
      mesenchymal stem cells and facilitate their differentiation has not been defined.
      Therefore, we sought to explore how endothelial cells might drive mesenchymal
      stem cells toward a smooth muscle fate. Our data show that cocultured endothelial
      cells induce smooth muscle cell differentiation in mesenchymal stem cells.
      Endothelial cells can promote a contractile phenotype, reduce proliferation, and
      enhance collagen synthesis and secretion. Our data show that Notch signaling is
      essential for endothelial cell-dependent differentiation, and this
      differentiation pathway is largely independent of growth factor signaling
      mechanisms. 

PMID- 24914694
TI  - Epidemiology: measurement matters--making musculoskeletal disease count.
AB  - Reliable estimates of disease burden support rational allocation of financial and
      human resources. Measurement is a powerful force for change as 'what gets
      measured gets done'. The global burden of musculoskeletal disease studies ensures
      visibility of these highly prevalent, disabling diseases. Now we must act to
      reduce disease burden.

PMID- 24914693
TI  - The eye: a window of opportunity in rheumatoid arthritis?
AB  - Rheumatoid arthritis (RA), the most common autoimmune disorder associated with
      dry eye syndrome, is also associated with sight-threatening ocular diseases such
      as peripheral ulcerative keratitis, scleritis and corneal melts. Tissue damage on
      the ocular surface of patients with RA is autoimmune-mediated. Findings from
      patients with dry eye have implicated defects in innate immunity (Toll-like
      receptors, S100A and resident antigen-presenting cells), cytokines, chemokines
      and T helper (TH)-cell subsets (including TH1 and TH17) in disease pathogenesis.
      Some of these features are probably important in dry eye related to RA, which can
      occur at a different time from articular disease and is more clinically severe
      than idiopathic dry eye. Ocular surface immune factors can be influenced by the
      systemic immune landscape. Depending on the severity of ocular inflammation in
      RA, treatment can include ciclosporin, topical corticosteroids, tacrolimus,
      autologous serum and systemic immunosuppression. Tissue damage is treated by
      inhibiting matrix metalloproteinases. Potential therapeutic strategies benefit
      from an improved understanding of ocular surface immunology, and include
      targeting of T-cell subsets, B-cell signalling or cytokines. 

PMID- 24914700
TI  - Fully-sprayed and flexible organic photodiodes with transparent carbon nanotube
      electrodes.
AB  - In this study, we demonstrate the feasibility of TCO-free, fully sprayed organic
      photodiodes on flexible polyethylene terephthalate (PET) substrates. Transparent
      conducting films of single-wall carbon nanotubes are spray deposited from aqueous
      solutions. Low roughness is achieved, and films with sheet resistance values of
      160 Omega/sq at 84% in transmittance are fabricated. Process issues related to
      the wetting of CNTs are then examined and solved, enabling successive spray
      depositions of a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
      (PEDOT:PSS) layer and a blend of regioregular poly(3-hexylthiophene-2,5-diyl) and
      [6,6]-phenyl C61 butyric acid methyl ester (PCBM). The active layer is then
      optimized, achieving a process yield above 90% and dark currents as low as 10(-4)
      mA/cm(2). An external quantum efficiency of 65% and high reproducibility in the
      performance of the devices are obtained. Finally, the impact of the
      characteristics of the transparent electrode (transmittance and sheet resistance)
      on the performances of the device are investigated and validated through a
      theoretical model and experimental data. 

PMID- 24914695
TI  - Intervertebral disc regeneration: do nutrients lead the way?
AB  - Strategies for the biological repair of intervertebral discs derive from the
      premise that disc degeneration results from impaired cellular activity and,
      therefore, that these structures can be induced to regenerate by implanting
      active cells or providing factors that restore normal cellular activity. In vitro
      and animal studies using this approach have had some success, but whether this
      success can be reproduced in degenerate human lumbar discs is unknown. Successful
      repair requires that the disc cells remain viable and active; they therefore need
      an adequate supply of nutrients. However, as the disc degenerates, the nutrient
      supply decreases, thereby limiting cell activity and viability. Current biologic
      approaches might place additional demands on an already precarious nutrient
      supply. Here, we discuss whether the loss of nutrients associated with disc
      degeneration limits the effectiveness of biologic approaches, and indicate that
      this neglected problem requires investigation if clinical application of such
      therapies is to succeed. 

PMID- 24914698
TI  - The multifactorial role of neutrophils in rheumatoid arthritis.
AB  - Of all cells implicated in the pathology of rheumatoid arthritis (RA),
      neutrophils possess the greatest cytotoxic potential, owing to their ability to
      release degradative enzymes and reactive oxygen species. Neutrophils also
      contribute to the cytokine and chemokine cascades that accompany inflammation,
      and regulate immune responses via cell-cell interactions. Emerging evidence
      suggests that neutrophils also have a previously unrecognised role in autoimmune
      diseases: neutrophils can release neutrophil extracellular traps (NETs)
      containing chromatin associated with granule enzymes, which not only kill
      extracellular microorganisms but also provide a source of autoantigens. For
      example, citrullinated proteins that can act as neoepitopes in loss of immune
      tolerance are generated by peptidylarginine deiminases, which replace arginine
      with citrulline residues, within neutrophils. Indeed, antibodies to citrullinated
      proteins can be detected before the onset of symptoms in patients with RA, and
      are predictive of erosive disease. Neutrophils from patients with RA have an
      increased tendency to form NETs containing citrullinated proteins, and sera from
      such patients contain autoantibodies that recognize these proteins. Thus, in
      addition to their cytotoxic and immunoregulatory role in RA, neutrophils may be a
      source of the autoantigens that drive the autoimmune processes underlying this
      disease. 

PMID- 24914701
TI  - Association between sarcopenia and metabolic syndrome in chronic obstructive
      pulmonary disease: the Korea National Health and Nutrition Examination Survey
      (KNHANES) from 2008 to 2011.
AB  - AIM: It is not clear whether the restrictive or obstructive pattern of spirometry
      is associated with metabolic syndrome. We investigated the associations between
      restrictive and obstructive spirometric patterns and metabolic risk factors using
      data from the Korea National Health and Nutrition Examination Survey (KNHANES).
      Additionally, we investigated whether sarcopenia is associated with metabolic
      syndrome in patients with chronic obstructive pulmonary disease (COPD). METHODS:
      Using data from KNHANES between 2008 and 2011, we enrolled 8,145 subjects (normal
      lung function: 6,077, obstructive spirometric pattern: 1,039, restrictive
      pattern: 1,029) aged >=40 years who underwent anthropometric measurement,
      laboratory tests, spirometry and estimation of appendicular muscle mass.
      Sarcopenia was defined as an appendicular skeletal muscle mass divided by body
      weight squared <2 SD below the sex-specific mean for the young reference group.
      RESULTS: Sarcopenia was found in 32.8% of male and 12.2% of female patients with
      COPD. The odds ratio (OR) of metabolic syndrome for the restrictive spirometric
      pattern in male was 1.29 (95% confidence interval [CI], 1.02-1.65), and that for
      obstructive pattern in males was 0.99 (95% CI, 0.79-1.26) after adjustments for
      covariables (female restrictive pattern (ORs, 1,45; 95% CI, 1.09-1.91) and female
      obstructive pattern (ORs 0.73; 95% CI, 0.49-1.09). After adjustment for other
      confounding factors, the risk of metabolic syndrome was higher in sarcopenic male
      (OR, 1.88; 95% CI, 1.27-2.77) with COPD than in those without sarcopenia.
      CONCLUSIONS: The restrictive spirometric pattern is associated with metabolic
      syndrome, and sarcopenia may contribute to the risk of metabolic syndrome in male
      patients with COPD.

PMID- 24914702
TI  - Risk factors for recurrence rate of ovarian endometriomas following a
      laparoscopic cystectomy.
AB  - AIM: Objective of the study was to evaluate the risk factors that influence the
      recurrence of endometrioma after laparoscopic excision. METHODS: A cross
      sectional study was performed at Arash University Hospital between 2009 and 2011
      on patients who had a minimum of one year of postoperative follow-up after
      undergoing a laparoscopic excision of an ovarian endometrioma. The patients had
      any prior surgery for ovarian endometriomas was excluded. Recurrence was defined
      as the presence of endometrioma more than 2 cm in size, detected by
      ultrasonography within 1 year of surgery. The variables including age at surgery,
      presence of infertility, uterine myoma, previous medical treatment of
      endometriosis, the size of the largest cyst at laparoscopy, unilateral or
      bilateral involvement, serum CA125 level, revised American Society for
      Reproductive Medicine (ASRM) score and stage, postoperative medical treatment and
      postoperative treatment were evaluated to assess their independent effects on the
      recurrence using logistic regression analysis. RESULTS: A total of 158 patients
      were admitted to the Surgery Unit for endometriomas cystectomy during the study
      period. After the initial assessment, 130 patients were eligible for the study.
      The overall rate of recurrence was 11.5% (15/130). Significant factors that were
      independently associated with higher recurrence were the size of the largest cyst
      (odds ratio [OR] =4, 95% confidence interval [95% CI] =1.6-10.4, P=0.002), a high
      rASRM score (OR=1.2, 95% CI=1-1.4, P=0.04) and woman age at surgery (OR=0.6, 95%
      CI=0.4-0.9, P=0.01). CONCLUSION: A high score of rASRM, large cyst size and young
      age at surgery were three significant factors that were associated with higher
      recurrence of endometriomas.

PMID- 24914703
TI  - Using in-situ polymerization of conductive polymers to enhance the electrical
      properties of solution-processed carbon nanotube films and fibers.
AB  - Single-walled carbon nanotubes/polymer composites typically have limited
      conductivity due to a low concentration of nanotubes and the insulating nature of
      the polymers used. Here we combined a method to align carbon nanotubes with in
      situ polymerization of conductive polymer to form composite films and fibers. Use
      of the conducting polymer raised the conductivity of the films by 2 orders of
      magnitude. On the other hand, CNT fiber formation was made possible with in-situ
      polymerization to provide more mechanical support to the CNTs from the formed
      conducting polymer. The carbon nanotube/conductive polymer composite films and
      fibers had conductivities of 3300 and 170 S/cm, respectively. The relatively high
      conductivities were attributed to the polymerization process, which doped both
      the SWNTs and the polymer. In-situ polymerization can be a promising solution
      processable method to enhance the conductivity of carbon nanotube films and
      fibers. 

PMID- 24914706
TI  - An unusual tracheal tumour.

PMID- 24914705
TI  - Deferred consent in a minimal-risk study involving critically ill subarachnoid
      hemorrhage patients.
AB  - INTRODUCTION: Alterations from first-party and surrogate decision-maker consent
      can enhance the feasibility of research involving critically ill patients.
      OBJECTIVE: To describe the use of a deferred-consent model to enable
      participation of critically ill patients in a minimal-risk biomarker study.
      METHODS: A prospective observational study was conducted in which serum biomarker
      samples were collected three times daily over the first 14 days following
      aneurysmal subarachnoid hemorrhage. Sample collection was initiated on intensive
      care unit admission and consent was obtained when research personnel could
      approach the patient or the patient's surrogate decision maker. RESULTS: Twenty
      seven patients were eligible for the study, of whom only five were capable of
      providing informed consent. Full consent was obtained for 21 (78%) patients
      through self- (n=4) and surrogate (n=17) consent. Partial consent or refusal
      (only permitting the collection of blood samples as a part of routine care or use
      of data) occurred in three patients. Among the 22 consents sought from
      surrogates, three (11%) refused participation. The refusals included the sickest
      patients in the cohort. Once consent was provided, no patient or surrogate
      withdrew consent before study completion. DISCUSSION: Use of a deferred consent
      model enabled participation of critically ill patients in a minimal-risk
      biomarker study with no withdrawals. CONCLUSIONS: Further research and enhanced
      awareness of the potential utility of hybrid models, including deferred consent
      in addition to patient or surrogate consent, in the conduct of low-risk and
      minimally interventional time-sensitive studies of critically ill patients are
      required.

PMID- 24914707
TI  - Recurrent pneumothoraces and facial papules: an insidious pulmonary cystic
      disease.

PMID- 24914708
TI  - Electrocatalytic oxygen evolution over supported small amorphous Ni-Fe
      nanoparticles in alkaline electrolyte.
AB  - The electrocatalytic oxygen evolution reaction (OER) is a critical anode reaction
      often coupled with electron or photoelectron CO2 reduction and H2 evolution
      reactions at the cathode for renewable energy conversion and storage. However,
      the sluggish OER kinetics and the utilization of precious metal catalysts are key
      obstacles in the broad deployment of these energy technologies. Herein,
      inexpensive supported 4 nm Ni-Fe nanoparticles (NiyFe1-yOx/C) featuring amorphous
      structures have been prepared via a solution-phase nanocapsule method for active
      and durable OER electrocatalysts in alkaline electrolyte. The Ni-Fe nanoparticle
      catalyst containing 31% Fe (Ni0.69Fe0.31Ox/C) shows the highest activity,
      exhibiting a 280 mV overpotential at 10 mA cm(-2) (equivalent to 10% efficiency
      of solar-to-fuel conversion) and a Tafel slope of 30 mV dec(-1) in 1.0 M KOH
      solution. The achieved OER activity outperforms NiOx/C and commercial Ir/C
      catalysts and is close to the highest performance of crystalline Ni-Fe thin films
      reported in the literature. In addition, a Faradaic efficiency of 97% measured on
      Ni0.69Fe0.31Ox/C suggests that carbon support corrosion and further oxidation of
      nanoparticle catalysts are negligible during the electrocatalytic OER tests.
      Ni0.69Fe0.31Ox/C further demonstrates high stability as there is no apparent OER
      activity loss (based on a chronoamperometry test) or particle aggregation (based
      on TEM image observation) after a 6 h anodization test. The high efficiency and
      durability make these supported amorphous Ni-Fe nanoparticles potentially
      applicable in the (photo)electrochemical cells for water splitting to make H2
      fuel or CO2 reduction to produce usable fuels and chemicals. 

PMID- 24914709
TI  - Maternal and fetal factors which influence cord blood glucose levels in term
      infants delivered by cesarean section.
AB  - AIM: To assess factors contributing to cord venous glucose homeostasis in term
      infants delivered by elective cesarean section. METHODS: Observational study of
      women-infant pairs at delivery. Biochemical and clinical data were collected
      about factors which might affect the levels of glucose, lactate, norepinephrine,
      epinephrine, cortisol, human growth hormone, glucagon, and insulin. RESULTS: In
      the context of this data-set, three models explained a substantial amount
      regarding the variation: 79% of the variation in cord glucose levels is explained
      by levels of maternal glucose, cord venous pH, and cord lactate; 77% of the
      variation of cord lactate is explained by levels of cord venous pH, valine,
      maternal lactate and glucose, and cord norepinephrine; and 71% of the variation
      in cord norepinephrine is explained by levels of cord venous pO2, maternal
      lactate, cord insulin, cord GABA (gamma-aminobutyric acid), cord lactate, cord
      epinephrine, cord norepinephrine sulfate, and cord valine. CONCLUSIONS: Term
      infants delivered by cesarean section are relatively hyperinsulinemic
      (insulin:glucose ratio of 2.4) and glucose levels are strongly associated with
      maternal glucose levels, cord pO2, and lactate levels. There were no associations
      with levels of cord glucose and levels of cortisol, epinephrine and lactate,
      which have been shown to be important contributors to postnatal glucose
      homeostasis in some infant groups.

PMID- 24914710
TI  - Cardiotocography patterns and risk of intrapartum fetal acidemia.
AB  - AIM: To identify cardiotocography (CTG) patterns associated with increased risk
      of intrapartum fetal acidemia. METHODS: A prospective observational cohort study
      of 1070 women with fetal scalp blood sampling (FBS) during labor was conducted at
      Karolinska University Hospital, Stockholm, Sweden. Women with a nonreassuring CTG
      pattern underwent FBS, and lactate concentration was measured at the bedside.
      Lactate concentrations >4.8 mmol/L were defined as fetal acidemia. A senior
      obstetrician, blinded to the lactate concentration at FBS, visually interpreted
      the CTG tracings that had prompted FBS. RESULTS: There were 2134 FBSs performed
      on 1070 laboring women, constituting 11% of all deliveries at this labor ward.
      The CTG patterns with the highest frequency of lactacidemia at FBS were late or
      severe variable decelerations combined with tachycardia (20%-25% at first FBS and
      33%-49% at last FBS). With a normal baseline fetal heart rate, normal
      variability, and absence of serious decelerations, the fetal scalp blood lactate
      concentration at the first FBS was normal in 97.5% of cases. The group with
      isolated reduced variability had no increased prevalence of acidemia and median
      lactate concentration did not differ from the normal group. CONCLUSION: Isolated
      reduced variability is in most cases not a sign of hypoxia. If development of
      hypoxia is ruled out with one FBS, this pattern does not require monitoring with
      repetitive FBSs throughout labor. Late decelerations and severe variable
      decelerations increase the risk for intrapartum fetal metabolic acidemia to the
      same extent. The combination of these decelerations and tachycardia was
      associated with the highest rate of fetal metabolic acidemia.

PMID- 24914711
TI  - Impact of maternal body mass index on the cesarean delivery rate in Germany from
      1990 to 2012.
AB  - AIMS: Maternal obesity is a risk factor for cesarean delivery (CD). The aim of
      this analysis was to determine the association between early-pregnancy body mass
      index (BMI) and the rate of CD over the past two decades. METHODS: We
      retrospectively analyzed data from the perinatal quality registry of singleton
      deliveries in the state of Hesse in Germany from 1990 to 2012. We divided the
      patients into groups according to the WHO criteria for BMI: underweight (<18.5),
      normal weight (18.5-<25), overweight (25-<30), obese class I (30-<35), obese
      class II (35-<40), and obese class III (>=40). RESULTS: The analysis included
      1,092,311 patients with available data regarding maternal BMI and mode of
      delivery. The CD rates for underweight (<18.5), normal weight (18.5-<25),
      overweight (25-<30), obese class I (30-<35), obese class II (35-<40), and obese
      class III (>=40) women increased from 14.4%, 16.1%, 19.5%, 22.3%, 25%, and 26.9%
      in the year 1990 to 27.9%, 31.4%, 38.8%, 45.1%, 50.2%, and 55.2% in the year
      2012, respectively (P<0.001). CONCLUSION: Maternal BMI in early pregnancy is
      linearly associated with the incidence of CD. We found a disproportionate
      increase of CD in morbidly obese women compared with the CD incidence in the
      reference BMI population over the past two decades.

PMID- 24914712
TI  - Street hawking among in-school adolescents in a south-western town in Nigeria:
      pattern, determinants and effects on school performance.
AB  - Street hawking is the commonest form of child labor in Nigeria. Although street
      hawking is very pervasive, there is the increasing need to fully understand its
      pattern and effects on those involved in hawking particularly adolescents who
      combine schooling with hawking. In Nigeria, data on the effects of street hawking
      on in-school adolescents are generally scanty. Therefore, the present study was
      undertaken in Ife Central Local Government Area (LGA) of Osun State, Nigeria to
      assess the pattern, determinants of street hawking among in-school adolescents
      and its effect on school performance. A cross-sectional study of 435 adolescents
      (aged 10-19) attending public secondary schools was done. Data were collected
      using facilitated self-administered questionnaires alongside a review of class
      records. Appropriate statistical analysis including multiple regression was done.
      Results showed mean age of respondents to be 14.6+/-2.1 years with prevalence of
      street hawking at 37.2%. Early adolescents (10-13 years) were more likely to
      engage in street hawking compared to their counterparts in late adolescence (aged
      17-19). Female adolescents and students of trading mothers were significantly
      more likely to engage in street hawking. Respondents engaged in street hawking
      were significantly more likely to have failed the last academic term examination.
      The findings from this study will be useful for stakeholders as they develop
      policies and programmes to address the challenge of street hawking among
      adolescent school goers.

PMID- 24914713
TI  - Energy substrate metabolism in pyruvate dehydrogenase complex deficiency.
AB  - Pyruvate dehydrogenase (PDH) deficiency is an inherited disorder of carbohydrate
      metabolism, resulting in lactic acidosis and neurological dysfunction. In order
      to provide energy for the brain, a ketogenic diet has been tried. Both the
      disorder and the ketogenic therapy may influence energy production. The aim of
      the study was to assess hepatic glucose production, lipolysis and resting energy
      expenditure (REE) in an infant, given a ketogenic diet due to neonatal onset of
      the disease. Lipolysis and glucose production were determined for two consecutive
      time periods by constant-rate infusions of [1,1,2,3,3-2H5]-glycerol and [6,6-2H2]
      glucose. The boy had been fasting for 2.5 h at the start of the sampling periods.
      REE was estimated by indirect calorimetry. Rates of glucose production and
      lipolysis were increased compared with those of term neonates. REE corresponded
      to 60% of normal values. Respiratory quotient (RQ) was increased, indicating a
      predominance of glucose oxidation. Blood lactate was within the normal range.
      Several mechanisms may underlie the increased rates of glucose production and
      lipolysis. A ketogenic diet will result in a low insulin secretion and reduced
      peripheral and hepatic insulin sensitivity, leading to increased production of
      glucose and decreased peripheral glucose uptake. Surprisingly, RQ was high,
      indicating active glucose oxidation, which may reflect a residual enzyme
      activity, sufficient during rest. Considering this, a strict ketogenic diet might
      not be the optimal choice for patients with PDH deficiency. We propose an
      individualised diet for this group of patients aiming at the highest glucose
      intake that each patient will tolerate without elevated lactate levels.

PMID- 24914714
TI  - The role of Toll-like receptors in multiple sclerosis and possible targeting for
      therapeutic purposes.
AB  - The interaction between the immune and nervous systems suggests invaluable
      mechanisms for several pathological conditions, especially neurodegenerative
      disorders. Multiple sclerosis (MS) is a potentially disabling chronic autoimmune
      disease, characterized by chronic inflammation and neurodegenerative pathology of
      the central nervous system. Toll-like receptors (TLRs) are an important family of
      receptors involved in host defense and in recognition of invading pathogens. The
      role of TLRs in the pathogenesis of autoimmune disorders such as MS is only
      starting to be uncovered. Recent studies suggest an ameliorative role of TLR3 and
      a detrimental role of other TLRs in the onset and progression of MS and
      experimental autoimmune encephalomyelitis, a murine model of MS. Thus, modulating
      TLRs can represent an innovative immunotherapeutic approach in MS therapy. This
      article outlines the role of these TLRs in MS, also discussing TLR-targeted
      agonist or antagonists that could be used in the different stages of the disease.

PMID- 24914715
TI  - Increased levels of serum gamma-glutamyltransferase and uric acid on metabolic,
      hepatic and kidney parameters in subjects at high altitudes.
AB  - BACKGROUND: Currently there are no studies on gamma-glutamyltransferase (gammaGT)
      levels at high altitude or on the relationship between gammaGT, uric acid and
      several dysfunctions. The aim of the study was to determine the association
      between serum gammaGT and uric acid levels in subjects at high altitude with
      hemoglobin, glycemia, and lipidic, hepatic and kidney markers. METHODS: The
      present study was performed in 487 subjects aged 30-75 years living at 4100 m of
      altitude. A venous blood sample was drawn from each subject to measure
      hemoglobin, glucose, and lipid levels and markers of liver and kidney function.
      Quartiles for serum gammaGT and uric acid were calculated and associated with
      different physiological variables. A p-value <0.05 was considered statistically
      significant. RESULTS: Serum gammaGT values were higher in men (38.35+/- 2.54
      IU/L) than in women (30.33+/-1.76 IU/L) (p<0.01). Similarly, serum uric acid
      levels were higher in men (5.78+/- 0.12 mg/dL) than in women (4.29+/-0.08 mg/dL;
      p<0.001). Serum gammaGT levels in the top quartile were associated with higher
      glycemia, overweight/obesity, increased levels of non-high-density lipoprotein
      (non-HDL) cholesterol, triglycerides, alanine aminotransferase, alkaline
      phosphatase, uric acid, creatinine, and hemoglobin. Levels of uric acid in the
      top quartile were associated with overweight/obesity, elevated non-HDL
      cholesterol, triglycerides, creatinine, gammaGT and hemoglobin. Higher arterial
      blood pressure was associated with high levels of uric acid but not with gammaGT
      levels. CONCLUSIONS: At high altitude, increased gammaGT levels were associated
      with hyperglycemia; increased uric acid levels were associated with
      overweight/obesity, hemoglobin, dyslipidemia, high blood pressure and kidney
      disease.

PMID- 24914716
TI  - Evaluation of chitosan based vaginal bioadhesive gel formulations for antifungal
      drugs.
AB  - The aim of the present study was to evaluate chitosan as a vaginal mucoadhesive
      gel base for econazole nitrate and miconazole nitrate. To this aim, different
      types of chitosan with different molecular masses and viscosity properties [low
      molecular mass chitosan (viscosity: 20,000 mPa s), medium molecular mass chitosan
      (viscosity: 200,000 mPa s), high molecular mass chitosan (viscosity: 800,000 mPa
      s)] have been used. First, rheological studies were conducted on chitosan gels.
      Mechanical, syringeability and mucoadhesive properties of chitosan gels were
      determined. Release profiles of econazole nitrate and miconazole nitrate from
      chitosan gels were obtained and evaluated kinetically. In addition, anticandidal
      activities of formulations were determined. Finally, vaginal retention of
      chitosan gels in rats was evaluated by in vivo distribution studies. Based on the
      results, it can be concluded that gels prepared with medium molecular mass
      chitosan might be effectively used for different antifungal agents in the
      treatment of vaginal candidiosis, since it has high mucoadhesiveness, suitable
      mechanical and release properties with good vaginal retention.

PMID- 24914717
TI  - Computational design of drug candidates for influenza A virus subtype H1N1 by
      inhibiting the viral neuraminidase-1 enzyme.
AB  - It is critical to seek potential alternative treatments for H1N1 infections by
      inhibiting neuraminidase-1 enzyme. One of the viable options for inhibiting the
      activity of neuraminidase- 1 is peptide drug design. In order to increase peptide
      stability, cyclization is necessary to prevent its digestion by protease enzyme.
      Cyclization of peptide ligands by formation of disulfide bridges is preferable
      for designing inhibitors of neuraminidase-1 because of their high activity and
      specificity. Here we designed ligands by using molecular docking, drug scan and
      dynamics computational methods. Based on our docking results, short polypeptides
      of cystein-arginine-methionine-tyrosine- -proline-cysteine (CRMYPC) and cysteine
      arginine-aspargine- phenylalanine-proline-cysteine (CRNFPC) have good residual
      interactions with the target and the binding energy DeltaGbinding of -31.7402 and
      -31.0144 kcal mol-1, respectively. These values are much lower than those of the
      standards, and it means that both ligands are more accessible to ligand-receptor
      binding. Based on drug scan results, both of these ligands are neither mutagenic
      nor carcinogenic. They also show good oral bioavailability. Moreover, both
      ligands show relatively stable molecular dynamics progression of RMSD vs. time
      plot. However, based on our metods, the CRMYPC ligand has sufficient hydrogen
      bonding interactions with residues of the active side of neuraminidase-1 and can
      be therefore proposed as a potential inhibitor of neuraminidase-1.

PMID- 24914718
TI  - Antibacterial and quorum sensing regulatory activities of some traditional
      Eastern-European medicinal plants.
AB  - The objective of this study was to screen extracts of twenty Eastern European
      medicinal plants, using wild-type and reporter Chromobacterium violaceum
      bioassays, for novel components that target bacterial cells and their quorum
      sensing (QS) communication systems. Three types of activity and their
      combinations were revealed: (i) direct antimicrobial growth-inhibitory activity,
      (ii) non-specific and specific pro-QS activities, (iii) anti-QS activity. Among
      seven plant extracts showing direct growth-inhibitory activity, the strongest
      effect was shown by Arctostaphylos uva-ursi (bearberry) leaves. Many plants
      stimulated violacein production by wild-type C. violaceum ATCC 31532 in a non
      specific manner, and only the herb Bidens tripartita (three-lobe beggarticks)
      contained compounds that mimic acyl-homoserine lactone and operated as a QS
      agonist. Anti-QS activity was found in eleven plants including Quercus robur
      (oak) cortex, Betula verrucosa (birch) buds and Eucalyptus viminalis (Manna Gum)
      leaves. Subsequent statistical analysis showed differences between antimicrobial
      and anti-QS activities, whereas both activities were defined by phylogenetic
      position of medical resource plant. Finally, extract from Quercus robur cortex
      revealed at least two fractions, showing different anti-QS mechanisms. These data
      confirm that multicomponent anti-infectious mechanisms are used by plants, which
      may be useful for drug development.

PMID- 24914719
TI  - HPLC method with monolithic column for simultaneous determination of irbesartan
      and hydrochlorothiazide in tablets.
AB  - A simple, sensitive and accurate HPLC method with high throughput has been
      developed and validated for the simultaneous determination of irbesartan (IRB)
      and hydrochlorothiazide (HCT) in combined pharmaceutical dosage forms. The
      proposed method employed, for the first time, a monolithic column in the
      analysis. Optimal chromatographic separation of the analytes was achieved on
      Chromolith((r)) Performance RP-18e column using a mobile phase consisting of
      phosphate buffer (pH 4)/acetonitrile (50:50, V/V) pumped isocratically at a flow
      rate of 1.0 mL min(-1). The eluted analytes were monitored with a UV detector set
      at 270 nm. Under the optimum chromatographic conditions, linear relationship with
      a good correlation coefficient (R >= 0.9997) was found between the peak area and
      the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and
      1-20 ng mL(-1). The limits of detection were 2.34 and 0.03 ng mL(-1) for IRB and
      HCT, respectively. The intra- and inter-assay precisions were satisfactory as the
      RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %.
      The proposed method had high throughput as the analysis involved a simple
      procedure and a very short run-time of < 3 min. The results demonstrated that the
      method is applicable in the quality control of combined pharmaceutical tablets
      containing IRB and HCT.

PMID- 24914720
TI  - Effect of selected catechins on doxorubicin antiproliferative efficacy and
      hepatotoxicity in vitro.
AB  - Catechins may influence both desirable and undesirable effects of many drugs. In
      this study, the in vitro effect of (+)-catechin, (-)-epicatechin, (-)
      epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate
      (EGCG) on the efficacy of anticancer drug doxorubicin (DOX) was studied in HCT-8
      cancer cells. Rat hepatocytes were used to study the influence of EGCG on DOX
      hepatotoxicity. Cell proliferation and viability were studied by 3-[4,5
      dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide and neutral red uptake
      test assays. Formation of reactive oxygen species (ROS) was determined using the
      dichlorofluorescein assay. All of the studied catechins (1-25 MUmol L(-1)) had no
      effect on the proliferation of intestinal cancer cells and did not affect the
      antiproliferative effect of DOX (1-8 MUmol L(-1)) in these cells. Moreover, EGCG
      at 25 MUmol L(-1) increased the viability of isolated hepatocytes and
      significantly protected these cells against DOX-induced toxicity and ROS
      production. Consumption of EGCG during DOX therapy seems to be safe and
      beneficial, since EGCG does not decrease DOX anticancer efficacy and could
      ameliorate DOX hepatotoxicity.

PMID- 24914721
TI  - Complexation of Z-ligustilide with hydroxypropyl-beta-cyclodextrin to improve
      stability and oral bioavailability.
AB  - To improve the stability and oral bioavailability of Z-ligustilide (LIG), the
      inclusion complex of LIG with hydroxypropyl- beta-cyclodextrin (HP-beta-CD) was
      prepared by the kneading method and characterized by UV-Vis spectroscopy,
      differential thermal analysis (DTA) and Fourier transform infrared (FTIR)
      spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the
      stoichiometry of the complex was 1:1. Stability of the inclusion complex against
      temperature and light was greatly enhanced compared to that of free LIG. Further,
      oral bioavailability of LIG and the inclusion complex in rats were studied and
      the plasma drug concentration-time curves fitted well with the non-compartment
      model to estimate the absolute bioavailability, which was 7.5 and 35.9 %,
      respectively. In conclusion, these results show that LIG/HP-beta-CD complexation
      can be of great use for increasing the stability and biological efficacy of LIG.

PMID- 24914722
TI  - Screening for impact of popular herbs improving mental abilities on the
      transcriptional level of brain transporters.
AB  - There are a number of compounds that can modify the activity of ABC (ATP-binding
      cassette) and SLC (solute carrier) transporters in the blood-brain barrier (BBB).
      The aim of this study was to investigate the effect of natural and synthetic
      substances on the expression level of genes encoding transporters present in the
      BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1). Our results showed
      that verapamil caused the greatest reduction in the mRNA level while other
      synthetic (piracetam, phenobarbital) and natural (codeine, cyclosporine A,
      quercetin) substances showed a selective inhibitory effect. Further, the extract
      from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription
      against selected transporters whereas the extract from Ginkgo biloba L. leaves
      resulted in an increase of the expression level of tested genes, except for mrp2.
      Extract from the aerial parts of Hypericum perforatum L. was the only one to
      cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that
      herbs can play an important role in overcoming the BBB and multidrug resistance
      to pharmacotherapy of brain cancer and mental disorders, based on the activity of
      selected drug-metabolizing enzymes and transporters located in the BBB.

PMID- 24914723
TI  - Synthesis and preliminary ex vivo evaluation of the spasmolytic activity of 1,3
      thiazolium- and 1,3,4-thiadiazolium-5-methylthio- and 5-thioacetate derivatives.
AB  - Seven new compounds have been synthetized in satisfactory yields (51-78 %)
      through the treatment of mesoionic 1,3-thiazolium-5-thiolate (4a-d) and 1,3,4
      thiadiazolium- 5-thiolate (10a,b) with chloroacetic acid or methyl iodide: 1,3,4
      thiadiazolium-5-methylthio- (11) and 5-thioacetate (12). The structure of the
      title compounds was elucidated by elemental analysis, IR, (1)H and (13)C NMR
      spectroscopy. The newly synthesized compounds 5a, 6a, 11 and 12 were evaluated
      for their ex vivo spasmolytic potential on four isolated smooth muscles (rat
      aorta and uterus, guinea pig ileum and trachea) and compared with scopolamine.
      Some of the compounds exhibited potent spasmolytic activity equal to or stronger
      than scopolamine.

PMID- 24914724
TI  - Enteric coating of granules containing the probiotic Lactobacillus acidophilus.
AB  - In the present study, a capsule formulation composed of enteric coated granules
      of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as
      enteric polymer. Optimization of the capsule formulation was achieved with a
      maximum viable cell count after 2 h of incubation in acid medium and
      disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in
      the capsules correlated with gastric juice resistance. The best protective
      qualities against artificial gastric juice were observed when capsules were
      prepared from granules composed of L. acidophilus, corn starch, lactose
      monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V) of Eudragit L30D
      55. Capsule formulation of L. acidophilus in edible broth medium suspension
      serves as a cheap alternative to the expensive freeze-drying procedure for
      preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55
      could protect probiotics from the acidic gastric environment and enhance the
      bioactivity of probiotics along with replacement of pathogenic microbes in human
      intestine.

PMID- 24914725
TI  - In vivo human skin penetration of (-)-epigallocatechin-3-gallate from topical
      formulations.
AB  - The aim of the study was to examine the effect of topical vehicles on the in vivo
      human stratum corneum penetration of the antioxidant and skin photoprotective
      agent (-)-epigallocatechin-3-gallate (EGCG). Model oil-in-water (o/w) emulsion
      and gel formulations containing 1 % (m/m) EGCG were prepared and subjected to
      photodegradation studies in order to select excipients that minimize the light
      instability of EGCG. The optimized emulsion and gel were applied to human
      volunteers and the EGCG percutaneous permeation was evaluated in vivo by the tape
      -stripping technique. No significant differences in the percentage of the
      applied EGCG dose diffused into the stratum corneum were observed between the o/w
      emulsion (36.1 +/- 7.5 %) and gel (35.5 +/- 8.1 %) preparations. However, the
      amount of EGCG permeated into the deeper region of human stratum corneum was
      significantly larger for the o/w emulsion compared to the gel. Therefore, the
      emulsion represents a suitable vehicle for topical delivery of EGCG.

PMID- 24914726
TI  - Analytical comparison of the new point-of-care troponin T immunoassay on
      AQT90Flex(r) analyzer (Radiometer) and the high-sensitivity troponin T
      immunoassay on ModularE170(r) (Roche Diagnostics).

PMID- 24914727
TI  - A new device for the prompt diagnosis of urinary tract infections.
AB  - BACKGROUND: Urinary tract infections (UTIs) are among the most common infectious
      diseases. RESULTS obtained from conventional microbiological analysis of urine
      and antibiotic susceptibility testing are available only after a few days,
      delaying precise diagnosis and appropriate therapy. Micro Biological Survey (MBS)
      srl (a spin-off of Roma Tre University, Rome, Italy) has developed and patented
      an automated colorimetric test for rapid bacterial counting. In a preliminary
      validation study it was demonstrated that the results obtained with the MBS
      method are equivalent to the results obtained with conventional culture-based
      microbiological analysis. METHODS: In this study, sterile urine samples were
      artificially contaminated with bacterial species that are most frequently
      responsible for UTIs. The MBS method was used to evaluate the presence of
      bacteria and their sensitivity to some of the most commonly used antibiotics in
      UTIs. RESULTS: The MBS method was able to detect in a few hours the presence or
      absence of bacteria at clinically significant concentrations (>105 CFU/mL), and
      to provide their susceptibility pattern to a limited panel of antibiotics.
      DISCUSSION: The results obtained demonstrate that the MBS point-of-care testing
      (POCT) device could be developed into a valuable aid for the management of UTIs,
      possibly addressing more precise diagnosis and appropriate therapy.

PMID- 24914728
TI  - Estimation of a predictor's importance by Random Forests when there is missing
      data: risk prediction in liver surgery using laboratory data.
AB  - Abstract In the last few decades, new developments in liver surgery have led to
      an expanded applicability and an improved safety. However, liver surgery is still
      associated with postoperative morbidity and mortality, especially in extended
      resections. We analyzed a large liver surgery database to investigate whether
      laboratory parameters like haemoglobin, leucocytes, bilirubin, haematocrit and
      lactate might be relevant preoperative predictors. It is not uncommon to observe
      missing values in such data. This also holds for many other data sources and
      research fields. For analysis, one can make use of imputation methods or
      approaches that are able to deal with missing values in the predictor variables.
      A representative of the latter are Random Forests which also provide variable
      importance measures to assess a variable's relevance for prediction. Applied to
      the liver surgery data, we observed divergent results for the laboratory
      parameters, depending on the method used to cope with missing values. We
      therefore performed an extensive simulation study to investigate the properties
      of each approach. Findings and recommendations: Complete case analysis should not
      be used as it distorts the relevance of completely observed variables in an
      undesirable way. The estimation of a variable's importance by a self-contained
      measure that can deal with missing values appropriately reflects the decreased
      relevance of variables with missing values. It can therefore be used to obtain
      insight into Random Forests which are commonly fit without preprocessing of
      missing values in the data. By contrast, multiple imputation allows for the
      assessment of a variable's relevance one would potentially observe in complete
      data situations, if imputation performs well. For the laboratory data, lactate
      and bilirubin seem to be associated with the risk of liver failure and
      postoperative complications. These relations should be investigated by future
      studies in more detail. However, it is important to carefully consider the method
      used for analysis when there are missing values in the predictor variables. 

PMID- 24914729
TI  - Herbal and dietary supplement use in Bangkok: a survey.
AB  - BACKGROUND: People living in Asian countries including Thailand are likely to use
      herbal and dietary supplements (HDS). However, there is limited evidence of their
      usage in Thailand. The objectives of this study were to determine (1) the
      prevalence of HDS usage amongst a general population in Bangkok; (2) patterns of
      HDS use; (3) reasons why Bangkok residents use HDS. METHODS: This cross-sectional
      survey recruited 400 Thai people aged 15 years or over at busy bus stops in
      Bangkok, Thailand, using convenience sampling. Data were collected via an
      interview regarding demographics, HDS usage and reasons of using HDS. Descriptive
      statistics, such as frequencies and percentages, were used to analyse the
      prevalence and the patterns of HDS use. RESULTS: The prevalence of HDS usage in
      the previous 6 months was 52%. The majority of people who took herbs used them to
      treat illnesses (58%), whereas the majority of people who took dietary
      supplements used them to promote well-being (65%). Respondents reported using HDS
      due to their efficacy (28%), wanting to try them (26%) and safety concerns with
      conventional medicines (15%). CONCLUSIONS: Health care providers should be aware
      of HDS use amongst Thai residents in Bangkok. Policy makers should educate people
      about appropriate HDS use.

PMID- 24914730
TI  - Accurate ab initio thermal rate constants for reaction of O((3)P) with H2 and
      isotopic analogues.
AB  - Semiclassical transition state theory, in combination with high accuracy quantum
      chemistry, is used to compute thermal rate constants from first principles for
      the O((3)P) + H2 reaction and its isotopic counterparts. In the temperature
      regime of 298-3500 K (which spans 8 orders of magnitude for rate constants), our
      theoretical results are in excellent agreement (within 5-15%) with all available
      experimental data from 298 to 2500 K but are somewhat too low (from 15 to 35%) at
      higher temperatures. Several possible reasons that might cause the degradation at
      high temperatures are discussed. Vibrational state-selected rate constants and
      their correlations with normal thermal rate constant are derived and are given in
      the Supporting Information. 

PMID- 24914731
TI  - Structures of delithiated and degraded LiFeBO(3), and their distinct changes upon
      electrochemical cycling.
AB  - Lithium iron borate (LiFeBO3) has a high theoretical specific capacity (220
      mAh/g), which is competitive with leading cathode candidates for next-generation
      lithium-ion batteries. However, a major factor making it difficult to fully
      access this capacity is a competing oxidative process that leads to degradation
      of the LiFeBO3 structure. The pristine, delithiated, and degraded phases of
      LiFeBO3 share a common framework with a cell volume that varies by less than 2%,
      making it difficult to resolve the nature of the delithiation and degradation
      mechanisms by conventional X-ray powder diffraction studies. A comprehensive
      study of the structural evolution of LiFeBO3 during (de)lithiation and
      degradation was therefore carried out using a wide array of bulk and local
      structural characterization techniques, both in situ and ex situ, with
      complementary electrochemical studies. Delithiation of LiFeBO3 starts with the
      production of LitFeBO3 (t ~ 0.5) through a two-phase reaction, and the subsequent
      delithiation of this phase to form Lit-xFeBO3 (x < 0.5). However, the large
      overpotential needed to drive the initial two-phase delithiation reaction results
      in the simultaneous observation of further delithiated solid-solution products of
      Lit-xFeBO3 under normal conditions of electrochemical cycling. The degradation of
      LiFeBO3 also results in oxidation to produce a Li-deficient phase D-LidFeBO3 (d ~
      0.5, based on the observed Fe valence of ~2.5+). However, it is shown through
      synchrotron X-ray diffraction, neutron diffraction, and high-resolution
      transmission electron microscopy studies that the degradation process results in
      an irreversible disordering of Fe onto the Li site, resulting in the formation of
      a distinct degraded phase, which cannot be electrochemically converted back to
      LiFeBO3 at room temperature. The Li-containing degraded phase cannot be fully
      delithiated, but it can reversibly cycle Li (D-Lid+yFeBO3) at a thermodynamic
      potential of ~1.8 V that is substantially reduced relative to the pristine phase
      (~2.8 V). 

PMID- 24914732
TI  - Evidence of a novel mevalonate pathway in archaea.
AB  - Isoprenoids make up a remarkably diverse class of more than 25000 biomolecules
      that include familiar compounds such as cholesterol, chlorophyll, vitamin A,
      ubiquinone, and natural rubber. The two essential building blocks of all
      isoprenoids, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate
      (DMAPP), are ubiquitous in the three domains of life. In most eukaryotes and
      archaea, IPP and DMAPP are generated through the mevalonate pathway. We have
      identified two novel enzymes, mevalonate-3-kinase and mevalonate-3-phosphate-5
      kinase from Thermoplasma acidophilum, which act sequentially in a putative
      alternate mevalonate pathway. We propose that a yet unidentified ATP-independent
      decarboxylase acts upon mevalonate 3,5-bisphosphate, yielding isopentenyl
      phosphate, which is subsequently phosphorylated by the known isopentenyl
      phosphate kinase from T. acidophilum to generate the universal isoprenoid
      precursor, IPP. 

PMID- 24914733
TI  - Simultaneous determination of glutathione, cysteine, homocysteine, and
      cysteinylglycine in biological fluids by ion-pairing high-performance liquid
      chromatography coupled with precolumn derivatization.
AB  - Biologically active low-molecular-mass thiols, mainly including glutathione
      (GSH), cysteine (Cys), homocysteine (Hcy), and cysteinylglycine (Cys-Gly), are
      important physiological components in biological fluids, and their analytical
      methods have gained continuous attention over recent years. We developed and
      validated a novel HPLC method for the quantification of GSH, Cys, Hcy, and Cys
      Gly in human plasma, urine, and saliva using 4-chloro-3,5-dinitrobenzotrifluoride
      as the derivatization reagent. Analyses were linear from 0.15 to 500 MUM with the
      coefficient regression range of 0.9987-0.9994. Detection limits ranged from 0.04
      to 0.08 MUM (S/N=3). The developed method was applied to quantification of four
      thiols in human biological fluids collected from five donors with the
      concentration range of 2.50-124.25 MUM, 0-72.81 MUM, and 0-4.25 MUM for plasma,
      urine, and saliva, respectively. The present method seemed to be an attractive
      choice for the determination of thiols in plasma, urine, and saliva.

PMID- 24914734
TI  - Label-free evaluation of myocardial infarction and its repair by spontaneous
      Raman spectroscopy.
AB  - Raman spectroscopy, which provides information about molecular species and
      structures of biomolecules via intrinsic molecular vibrations, can analyze
      physiological and pathological states of tissues on the basis of molecular
      constituents without staining. In this study, we analyzed Raman spectra of
      myocardial infarction and its repair in rats using the hypothesis that the
      myocardium in the course of myocardial infarction and its repair could be
      recognized by spontaneous Raman spectroscopy on the basis of chemical changes in
      myocardial tissues. Raman spectra were acquired from unfixed frozen cross
      sections of normal and infarcted heart tissues upon excitation at 532 nm. Raman
      spectra of the infarcted tissues were successfully obtained at characteristic
      time points: days 2, 5, and 21 after coronary ligation, at which the main
      components of the infarcted region were coagulation necrosis, granulation tissue,
      and fibrotic tissue, respectively. The latent variable weights calculated by a
      multivariate classification method, partial least-squares-discriminant analysis
      (PLS-DA), revealed fundamental information about the spectral differences among
      the types of tissues on the basis of molecular constituents. A prediction model
      for the evaluation of these tissue types was established via PLS-DA. Cross
      validated sensitivities of 99.3, 95.3, 96.4, and 91.3% and specificities of 99.4,
      99.5, 96.5, and 98.3% were attained for the discrimination of normal, necrotic,
      granulation, and fibrotic tissue, respectively. A two-dimensional image of a
      marginal area of infarction was successfully visualized via PLS-DA. Our results
      demonstrated that spontaneous Raman spectroscopy combined with PLS-DA is a novel
      label-free method of evaluating myocardial infarction and its repair. 

PMID- 24914735
TI  - Iron-catalysed, general and operationally simple formal hydrogenation using
      Fe(OTf)3 and NaBH4.
AB  - An operationally simple and environmentally benign formal hydrogenation protocol
      has been developed using highly abundant iron(iii) salts and an inexpensive,
      bench stable, stoichiometric reductant, NaBH4, in ethanol, under ambient
      conditions. This reaction has been applied to the reduction of terminal alkenes
      (22 examples, up to 95% yield) and nitro-groups (26 examples, up to 95% yield).
      Deuterium labelling studies indicate that this reaction proceeds via an ionic
      rather than radical mechanism. 

PMID- 24914737
TI  - Computational study of structural properties of lithium cation complexes with
      carbamate-modified disiloxanes.
AB  - Lithium cation solvation structures [Li(S)(n=1-4)](+) with ligands of cyclic or
      noncyclic carbamate-modified disiloxanes are optimized at B3LYP level of theory
      and compared to their corresponding simplified carbamates and to the organic
      carbonates ethylene carbonate (EC) and dimethyl carbonate (DMC). The
      electrostatic potentials (ESP) of these investigated carbonyl-containing solvents
      are mapped on the electron density surface. The maximum ESP is located at the C=O
      oxygen, whereas the disiloxane functionality represents an unpolar residue.
      Natural Bond Orbitals (NBO) analysis reveals strong n(N) ->pi(C[double bond,
      length as m-dash]O) donor-acceptor interactions in carbamates which outrun
      dipolar properties. As a result, higher total binding energies (DeltaE(B)) for
      solvation of Li(+) in carbamates (-148 kcal mol(-1)) are found than for
      carbonates (-137 kcal mol(-1)). Furthermore, the disiloxane moiety with its Si-O
      bond is stabilized by n(O) ->sigma*(Si-C) hyperconjugation that provides
      additional electron density to a nearby SiCH3 methyl group thus supporting an
      additional SiCH2-H...Li(+) coordination. The formation of all investigated
      solvation structures is exothermic. Owing to steric hindrance of noncyclic
      carbonyl-containing ligands and the bulky disiloxane functionality, the solvation
      structure [Li(S)3](+) is the preferred structure according to Gibbs free energy
      DeltaG(B) results.

PMID- 24914736
TI  - Impact of physical maltreatment on the regulation of negative affect and
      aggression.
AB  - Physically maltreated children are at risk for developing externalizing
      behavioral problems characterized by reactive aggression. The current experiment
      tested the relationships between individual differences in a neural index of
      social information processing, histories of child maltreatment, child negative
      affect, and aggressive behavior. Fifty boys (17 maltreated) performed an emotion
      recognition task while the P3b component of the event-related potential was
      recorded to index attention allocation to angry faces. Children then participated
      in a peer-directed aggression task. Negative affect was measured by recording
      facial electromyography, and aggression was indexed by the feedback that children
      provided to a putative peer. Physically maltreated children exhibited greater
      negative affect and more aggressive behavior, compared to nonmaltreated children,
      and this relationship was mediated by children's allocation of attention to angry
      faces. These data suggest that physical maltreatment leads to inappropriate
      regulation of both negative affect and aggression, which likely place maltreated
      children at increased risk for the development and maintenance of externalizing
      behavior disorders. 

PMID- 24914738
TI  - Aminoazabenzimidazoles, a novel class of orally active antimalarial agents.
AB  - Whole-cell high-throughput screening of the AstraZeneca compound library against
      the asexual blood stage of Plasmodium falciparum (Pf) led to the identification
      of amino imidazoles, a robust starting point for initiating a hit-to-lead
      medicinal chemistry effort. Structure-activity relationship studies followed by
      pharmacokinetics optimization resulted in the identification of 23 as an
      attractive lead with good oral bioavailability. Compound 23 was found to be
      efficacious (ED90 of 28.6 mg.kg(-1)) in the humanized P. falciparum mouse model
      of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast
      killing profile that is comparable to that of chloroquine. This series
      demonstrates no cross-resistance against a panel of Pf strains with mutations to
      known antimalarial drugs, thereby suggesting a novel mechanism of action for this
      chemical class.

PMID- 24914739
TI  - Chinese tobacco industry promotional activity on the microblog Weibo.
AB  - BACKGROUND: Although China ratified the WHO Framework Convention on Tobacco
      Control [FCTC] in 2005, the partial ban on tobacco advertising does not cover the
      internet. Weibo is one of the most important social media channels in China,
      using a format similar to its global counterpart, Twitter. The Weibo homepage is
      a platform to present products, brands and corporate culture. There is great
      potential for the tobacco industry to exploit Weibo to promote products. METHODS:
      Seven tobacco industry Weibo accounts that each had more than 5000 fans were
      selected to examine the content of Weibos established by tobacco companies or
      their advertising agents. RESULTS: Of the 12073 posts found on the seven
      accounts, 92.3% (11143) could be classified into six main themes: traditional
      culture, popular culture, social and business affairs, advertisement, public
      relations and tobacco culture. Posts under the theme of popular culture accounted
      for about half of total posts (49%), followed by 'advertisement' and 'tobacco
      culture' (both at 12%), 'traditional culture' and 'public relations' (both at
      11%), and finally 'social and business affairs' (5%). 33% of posts included the
      words 'cigarette' or 'smoking' and 53% of posts included the tobacco brand name,
      indicating that tobacco companies carefully construct the topic and content of
      posts. CONCLUSIONS: Weibo is an important new online marketing tool for the
      Chinese tobacco industry. Tobacco industry use of Weibo to promote brands and
      normalize smoking subverts China's ratification of the WHO FCTC. Policy to
      control tobacco promotion needs reforming to address this widespread
      circumvention of China's tobacco advertising ban.

PMID- 24914740
TI  - A simple method to identify patients on long-term warfarin who may derive the
      most benefit from new oral anticoagulants.
AB  - In many countries, new oral anticoagulants are only covered for patients with
      suboptimal anticoagulation control on vitamin K antagonists (VKAs). The quality
      of VKA management is often reported using the time in therapeutic range (TTR). We
      sought to predict a TTR 65% or less using a surrogate measure [number of changes
      in VKA dose and number of international normalized ratio (INR) tests] that could
      be easily determined by primary care physicians. This cross-sectional study
      included consecutive patients whose VKA therapy was managed in a specialized
      anticoagulation clinic. Patients were dichotomized according to their TTR in the
      past 6 months (TTR > or <= 65%). The ability of the number of INR tests and VKA
      dose changes to predict TTR group was assessed using receiver-operating
      characteristics (ROC) curve analysis. The analyses included 1381 patients with a
      median age of 63 years. The mean TTR was 81% (interquartile range 70-90) and
      17.4% of patients had a TTR 65% or more. Based on the ROC curve, patients were
      stratified according to whether they had either 3 or more dose changes or 9 or
      more INR tests within the last 6 months. The sensitivity to identify patients
      with TTR 65% or less was 87% and the specificity was 63%. The number of dose
      changes and the number of INR tests might be used as indicators of TTR; they
      could offer a simple way for clinicians to identify patients who are good
      candidates for the new oral anticoagulants. However, external validation studies
      in different clinical settings are needed to confirm these findings.

PMID- 24914741
TI  - A case of a severe factor XI deficiency in patient undergoing hemodialysis
      without the use of heparin.
AB  - Factor XI (FXI) deficiency is a rare hematologic disease, and shows a less severe
      bleeding tendency compared with what is generally observed in patients with
      hemophilia A and B. FXI has received a lot of attention in recent years as a new
      therapeutic target. Here, we present a case of 59-year-old male patient with
      chronic renal failure. The patient was found to have a markedly prolonged
      activated partial thromboplastin time (aPTT) during routine preoperative blood
      test before an arteriovenous fistula surgery. Finally, he was diagnosed with FXI
      deficiency. More than 6 months after the start of hemodialysis, no sign of blood
      clotting in the extracorporeal circuit has been observed. Of note, the patient
      did not receive any anticoagulant during hemodialysis, and he did not show any
      bleeding tendency even with aPTT more than 120 s and FXI activity below 3% of
      normal in a patient with renal failure. To our knowledge, this is the first case
      report to demonstrate FXI deficiency exhibiting anticoagulant effect equivalent
      to heparin in dialysis.

PMID- 24914743
TI  - Two novel mutations identified in a type 3 von Willebrand disease patient.
AB  - von Willebrand disease (VWD) is the most common inherited bleeding disorder in
      humans. Caused by mutations in the von Willebrand factor (VWF) gene, these
      defects result in qualitatively abnormal variants of VWF (classi&filig;ed as type
      2 VWD) or a decrease in VWF levels (types 1 and 3 VWD). Type 3 VWD is the most
      severe type and usually presented with undetectable VWF level. In this report, we
      describe a type 3 VWD patient. Molecular analysis of the whole VWF gene reveals
      two novel mutations, c.2480G>A (p.C827Y) in exon 19 and c.3897delT in exon 28. 

PMID- 24914742
TI  - Novel mutations (gammaTrp208Leu and gammaLys232Thr) leading to congenital
      hypofibrinogenemia in two unrelated Chinese families.
AB  - Congenital hypofibrinogenemia is a rare disorder caused by heterozygous mutations
      in the fibrinogen genes. The aim of this study was to elucidate the molecular
      defects in two unrelated families with hypofibrinogenemia. The proband from
      family A was a 19-year-old Chinese boy who was suffering from cervical
      lymphadenitis. A low plasma fibrinogen concentration (0.63 g/l by Clauss method
      and 0.77 g/l by immunoturbidimetry) was found in routine clotting tests. Further
      gene analysis revealed a heterozygous g.5792 G>T mutation in exon 7 of the FGG,
      leading to a novel Trp208Leu change in the gamma D domain. This mutation was also
      found in other family members with low fibrinogen levels. The proposita from
      family B was a 37-year-old female who suffered from recurrent shoulder pain for 7
      years. Routine clotting studies revealed that her prothrombin time was 15.5 s
      (normal range: 11.8-14.8 s) and thrombin time was 22.8 s (normal range: 14.0-20.0
      s), and the fibrinogen concentration in her plasma was only 0.64 g/l by Clauss
      method and 0.79 g/l by immunoturbidimetry. A heterozygous A>C transition at
      nucleotide 5864 of FGG was found in the gamma chain, causing a Lys232Thr
      substitution in the fibrinogen. Further sequencing established that her mother,
      son, brother and nephew were also heterozygous for the mutation.

PMID- 24914744
TI  - Treatment of muscle haematomas in haemophiliacs with special emphasis on
      percutaneous drainage.
AB  - Between 10 and 23% of bleeding episodes in the musculoskeletal system of
      haemophilia patients occur in the muscles. Until now, the most widely accepted
      treatment for muscle haematomas in patients with haemophilia has been a
      combination of rehabilitation and intravenous infusion of replacement clotting
      factor, until the haematoma completely disappears. The only way to prevent muscle
      bleeds in haemophilia is primary haematological prophylaxis (from cradle to
      college). Home treatment is currently the standard of care for patients with
      severe haemophilia. When a muscle bleed is suspected, confirmation must be
      achieved by means of imaging tests (ultrasound, MRI, CT). Then, immediate (early)
      enhanced on-demand haematological treatment must be started until the full
      disappearance of the haematoma. If untreated, muscle bleeds can cause
      complications such as nerve injury, compartment syndrome, myositis ossificans,
      pseudotumour, and even infection (abscess). Currently, the literature for muscle
      hematomas in the nonhaemophiliac population suggests that ultrasound-guided
      percutaneous drainage, or surgical drainage performed as open surgery if
      percutaneous drainage fails, could be beneficial in terms of achieving better and
      faster symptom relief. Ultrasound-guided haematoma evacuation is a well tolerated
      procedure. However, the proportion of unsuccessful evacuations and hematoma
      recurrence is substantial (13%). Such a rate of unsuccessful evacuation is
      because of excessive density and/or viscosity of the content. Ideally, haematoma
      evacuation must be performed before 3-5 days since the beginning of the muscular
      bleed. Although we have not found publications about ultrasound-guided
      decompression of muscle haematomas in haemophilia, the current status of progress
      in both the haematological and ultrasound fields leads us to think that this
      technique should be increasingly considered for the treatment of haemophilia
      patients, especially in the case of large haematomas in the liquid phase.

PMID- 24914745
TI  - Update on primary cleft lip rhinoplasty.
AB  - PURPOSE OF REVIEW: The optimal timing and techniques utilized to address the
      nasal deformity of the cleft lip continue to raise challenges and debate for the
      surgical community. There has been a shift in the paradigm addressing the nasal
      deformity to a more proactive approach. The goal of this article is to provide an
      update of the latest techniques for primary cleft rhinoplasty. RECENT FINDINGS: A
      medical literature search was performed specifically targeting primary cleft
      rhinoplasty in order to review the current strategies implemented, including
      presurgical orthopedics, surgical incisions, reconstruction, and suture
      techniques. SUMMARY: Today primary rhinoplasty is performed widely with many
      investigators reporting improved esthetic and functional outcomes. Both endonasal
      and external rhinoplasty approaches have been described for the unilateral and
      bilateral deformity. Goals include closure of the nasal floor and sill, symmetry
      of the alar base, and symmetry of the lower lateral cartilages with appropriate
      projection of the dome. Recent literature supports that rhinoplasty performed at
      the time of the primary cleft lip closure may reduce the frequency and magnitude
      of required intermediate and definitive rhinoplasty operations.

PMID- 24914746
TI  - Electrochemical control of two-color emission from colloidal dot-in-bulk
      nanocrystals.
AB  - Colloidal "dot-in-bulk" nanocrystals (DiB NCs) consist of a quantum confined core
      embedded into a bulklike shell of a larger energy gap. The first reported example
      of this class of nanostructures are CdSe/CdS DiB NCs that are capable of
      producing tunable two-color emission under both weak continuous-wave optical
      excitation and electrical charge injection. This property is a consequence of a
      Coulomb blockade mechanism, which slows down dramatically intraband relaxation of
      shell-localized holes when the core is already occupied by a hole. Here, we
      demonstrate electrochemical control of dual emission from DiB NCs. Spectro
      electrochemical (SEC) experiments are used to tune and probe the
      photoluminescence (PL) intensity and branching between the core and the shell
      emission channels as a function of applied electrochemical potential (VEC). To
      interpret the SEC data we develop a model that describes the changes in the
      intensities of the shell and core PL bands by relating them to the occupancies of
      electron and hole traps. Specifically, application of negative electrochemical
      potentials under which the Fermi level is shifted upward in energy leads to
      passivation of electron traps at the surface of the CdS shell thereby increasing
      the total PL quantum yield by favoring the shell emission. Simultaneously, the
      emission color changes from red (VEC = 0) through yellow to green (VEC = -1).
      Time-resolved PL measurements indicate that as the Fermi level approaches the NC
      conduction band-edge electrons are injected into the NC quantized states, which
      leads to typical signatures of negative trions observed under optical excitation.
      Application of positive potentials leads to activation of electron traps, which
      quenches both core and shell PL and leads to the reduction of the overall PL
      quantum efficiency. A high sensitivity of emission intensity (especially
      pronounced for the shell band) and the apparent emission color of DiB NCs to
      local electrochemical environment can enable interesting applications of these
      novel nanostructures in areas of imaging and sensing including, for example,
      ratiometric probing of intracellular pH.

PMID- 24914747
TI  - Testing Abeta toxicity on primary CNS cultures using drug-screening microfluidic
      chips.
AB  - Open microscale cultures of primary central nervous system (CNS) cells have been
      implemented in microfluidic chips that can expose the cells to physiological
      fluidic shear stress conditions. Cells in the chips were exposed to differently
      aggregated forms of beta-amyloid (Abeta), i.e. conditions mimicking an
      Alzheimer's Disease environment, and treated with CNS drugs in order to assess
      the contribution of glial cells during pharmacological treatments. FTY720, a drug
      approved for the treatment of Multiple Sclerosis, was found to play a marked
      neuroprotective role in neuronal cultures as well as in microglia-enriched
      neuronal cultures, preventing neurodegeneration after cell exposure to neurotoxic
      oligomers of Abeta. 

PMID- 24914748
TI  - Serum uric acid levels and metabolic syndrome.
AB  - OBJECTIVE: To investigate the relationship among serum uric acid levels and
      metabolic syndrome. MATERIALS AND METHODS: Anthropometric parameters, serum uric
      acid and metabolic parameters were evaluated in 139 subjects. RESULTS: Serum uric
      acid levels were significantly higher in subjects with than without metabolic
      syndrome (p < 0.0001), and raised gradually with the increasing number of
      metabolic syndrome components (p for trend < 0.0001). Serum uric acid
      significantly correlated with various anthropometric and serum metabolic
      parameters. DISCUSSION AND CONCLUSIONS: Serum uric acid levels were higher in
      individuals with rather than without metabolic syndrome and raised gradually as
      the number of metabolic syndrome components increased. The relationship between
      serum uric acid levels and various metabolic parameters suggests that uric acid
      might be considered as a component of metabolic syndrome. CONTEXT: Hyperuricemia
      is a common finding in patients with the metabolic syndrome. Recent studies
      indicated that hyperuricemia may be also a predictor of metabolic syndrome
      development.

PMID- 24914749
TI  - How does the milk removal method affect teat tissue and teat recovery in dairy
      ewes?
AB  - The aim of this work was to study how machine milking (MM) carried out in
      suitable conditions affects teat wall thickness and teat canal length and their
      return after milking to pre-milking conditions, in comparison with other milk
      extraction methods considered biological referents: lamb suckling (LS), milk
      removal by catheter (RC) and hand milking (HM). Three Latin square experiments
      were designed, using 11 ewes in the first experiment (LS), 13 in the second (RC)
      and 12 in the third (HM). Each of the Latin squares was divided into two periods:
      in the first, the left gland of each animal was machine milked and the
      corresponding treatment (LS, RC and HM) was applied to the right gland.
      Subsequently, in the second period the extraction methods were interchanged.
      During the experimental period, 4 sampling days were carried out (2 in each
      experimental period), where ultrasound scans were taken before (B) and
      immediately after milking (A) and at 1 (1 h), 2 (2 h), 3 (3 h), 4 (4 h), 6 (6 h),
      8 (8 h) and 10 (10 h) hours after milking finished. Teat wall thickness (TWT),
      teat wall area (TWA), teat end area (TEWA) and teat canal length (TCL) were
      measured in all the ultrasound images. MM increased TWT after milking compared
      with RC. TWT, TWA, TEWA and TCL were lower (P<0.05) in HM than in MM. No
      significant differences (P>0.05) were found between LS and MM for any variable.
      The extraction method affected the recovery time of the variables, with total
      teat recovery at 6 h after RC and 4 h after HM. In the case of LS, the TEWA and
      TCL values were recovered sooner, as of 3 h. Teat recovery time after MM was
      similar to the extraction method with which it was compared in each experiment.
      Thus, considering the similar increase in wall thickness and their recovery time
      compared with the reference methods, it was concluded that machine milking,
      carried out in optimum conditions and respecting the time interval between
      milkings usually applied on sheep farms (8-12 h), would not affect teat
      integrity. Moreover, given the variability observed in teat thickness recovery
      time between the different experiments, further research should be carried out to
      study which factors intrinsic and extrinsic to the animal may affect the teat
      wall thickness and recovery time after machine milking.

PMID- 24914750
TI  - Masson tumor in the eyelid.
AB  - Intravascular papillary endothelial hyperplasia (Masson tumor) is an uncommon
      vascular lesion that rarely affects the periorbital region. Differential
      diagnosis from some malignant periorbital tumors is challenging and depends
      mostly on histopathologic confirmation. We present a case with elevated,
      multilobular lower eyelid lesion that turned out to be intravascular papillary
      endothelial hyperplasia. 

PMID- 24914751
TI  - The volume prediction on the experimental design hippocampus using stereological
      method.
AB  - The application of stereologic techniques to the analysis of the nervous system
      has greatly contributed to the evaluation of the normal and pathological anatomy
      of the aging brain. Currently, the hippocampus still holds secrets about the
      aging process. Experimental researches on hippocampus morphology may contribute
      to the future researches. This study presents the volume and weight of left
      hippocampus using a stereological technique on light microscope. The mean weight
      of the encephalon without cerebellum was 6.1 +/- 0.1 g. The mean weight and the
      volume of the hippocampus were (mean +/- SD) 0.28 +/- 0.02 g and 0.28 +/- 0.02
      cm3, respectively. The mean coefficient of error for the stereological volume
      estimation of the hippocampus was 0.03. The individual volume estimation of the
      subjects may be achieved by the Cavalieri method. Investigators believed that the
      findings and the applied technique in this study may be useful for clinicians.

PMID- 24914752
TI  - Soft tissue changes after posterior impaction and setback of the maxilla with Le
      Fort I osteotomy in skeletal class III patients.
AB  - The purpose of this retrospective study was to evaluate the changes in the upper
      lip (UL) by posterior impaction and setback (PI-SB) of the maxilla. The samples
      consisted of 29 skeletal Class III patients (10 men and 19 women) who received
      bimaxillary surgery including PI-SB of the maxilla after Le Fort I osteotomy.
      Lateral cephalograms were taken at 1 week before surgery (T0) and 6 months after
      surgery (T1). After linear and angular changes of the hard and soft tissue
      variables were measured, the paired t test, Pearson correlation test, and
      univariate linear regression analysis were performed for statistical analyses.
      The changes in the hard tissue landmarks were as follows: ANS, U1E, and U6MBC
      moved backward (P < 0.001, P < 0.001, and P < 0.05, respectively) and upward (P <
      0.001, P < 0.01, and P < 0.001, respectively), whereas A point, U1A, and PNS
      moved upward only (P < 0.01, P < 0.01, and P < 0.001, respectively). In terms of
      the soft tissue change, although subnasale (Sn) did not show significant change,
      pronasale (Pn) moved upward (P < 0.05); UL, backward and downward (all P <
      0.001); and Stms (stomodium-superius), backward (P < 0.001). There were
      significant correlations between the horizontal change of the UL and that of A
      point and U1E (P < 0.01, P < 0.05). The regression equation of the horizontal
      change of UL and U1E was [INCREMENT]UL-vertical reference line (VRL) = (0.476 *
      [INCREMENT]U1E-VRL) - 0.581 (P < 0.05). If U1E moves backward by 3 mm and 5 mm,
      the UL is predicted to move backward by 0.9 mm and 1.8 mm, respectively. These
      results might provide a guideline in diagnosis and treatment planning for
      maxillary surgery with PI-SB. 

PMID- 24914753
TI  - Removal of orbital-maxillary sinus-pterygopalatine fossa foreign body with
      external and endoscopic combined approach.
AB  - Craniofacial trauma involving the pterygopalatine fossa region is reported to be
      rare. We present a case of a foreign body involving the orbit, maxillary sinus,
      and pterygopalatine fossa in a 4-year-old boy. The object was a reed shaft. Three
      dimensional computed tomographic scans and magnetic resonance imaging were done
      to make a correct diagnosis and to apply the best surgical treatment. The
      Caldwell-Luc approach combined with endoscopic approach was applied to remove all
      the fragments of the foreign body, which had been decayed in the human body. One
      month later, the patient showed satisfactory aesthetic and functional results. 

PMID- 24914754
TI  - Exploring the safety range via the transoral approach to the craniovertebral
      junction.
AB  - Surgeries via the transoral approach are widely used to deal with lesions near
      the craniovertebral junction. For this approach, the pharyngeal tubercle is an
      important landmark to identify the midline. The foramen lacerum, another
      important anatomic area where some crucial structures pass, is close to the
      pharyngeal tubercle. In the current study, we measured relevant distances and
      angles on 120 adults without brain diseases to estimate the safety range of the
      transoral approach. Distances between the pharyngeal tubercle and the foramen
      lacerum were expressed as mean (SD) and 95% confidence interval. Angles between
      the straight lines, which pass through the pharyngeal tubercle and the foramen
      lacerum, and the sagittal plane, as well as the horizontal plane, were also
      presented as mean (SD) and 95% confidence interval. As regards the 95% confidence
      intervals of the angles and the distances, which were used to define the safety
      range, no differences were observed between the right side and the left side.
      During such surgeries, if the midline is defined as a datum line, it is less
      likely for surgeons to destroy adjacent structures when moving within 36.30
      degrees on the sagittal plane and 45.00 degrees on the horizontal plane once they
      find the pharyngeal tubercle. It is also safe to move within 16.20 mm from the
      pharyngeal tubercle. With these data, we have successfully defined the safety
      range of the surgery, which may help operators choose proper instruments in
      surgery and avoid injuries to important structures. Moreover, operators may use
      these data to position the pharyngeal tubercle so as not to deviate from the
      midline. 

PMID- 24914755
TI  - Mandibular distraction osteogenesis with newly designed electromechanical
      distractor.
AB  - BACKGROUND: The purposes of this study were to design a fully automatic
      electromechanical distractor for continuous mandibular distraction osteogenesis
      and to investigate the efficacy of this newly developed distractor on sheep
      mandible model. METHODS: Five sheep underwent unilateral mandibular osteotomy,
      and the mechanical component of electromechanical distractor was fixed on both
      sides of the osteotomy site using pins. After a 5-day latency period, the
      electromechanical distractor was activated at a rate of 0.30 mm per 8 hours using
      an electronic control unit. The bone was lengthened for 20 days without any
      intervention to the electromechanical distractor. The animals were killed on the
      sixth week of the consolidation period, and 5 distracted mandibles were examined
      through macroscopic observation and computed tomography. Distracted bone length
      was measured through computed tomography on sagittal slices. RESULTS: The device
      was tolerated by the distraction process without complications in all animals.
      New callus formation was observed on the distraction gap. Radiologic evaluation
      showed new callus formation in the distraction gap. New callus length was found
      to be, in average, 18.28 mm. CONCLUSIONS: In this preliminary study, a newly
      designed electromechanical distractor was successfully used for mandible
      distraction, which mainly provided a continuous lengthening during activation
      period spontaneously without any intervention. We think that the clinical
      application of this electromechanic distractor may provide patient comfort during
      distraction. Moreover, electromechanical distractor has the potential for high
      resolution movement capacity when compared with annual distraction. The promising
      results from this prototype are encouraging to further investigations for human
      applications.

PMID- 24914756
TI  - Osteointegration of a bisphenol-a-glycidyl-dimethacrylate composite and its use
      in anterior skull base defects: an experimental study in an experimental design
      model of cerebrospinal fluid leak.
AB  - OBJECT: Promising clinical results were reported in watertight closure of
      anterior skull base defects (ASBDs) with bisphenol-a-glycidyl-dimethacrylate (bis
      GMA)-based materials to prevent the cerebrospinal fluid leaks. However,
      interrelation of these materials with surrounding bones in histologic level,
      referred to as the osteointegration, has not been reported in the anterior skull
      base. In addition, an illustrative case with an ASBD that was repaired using a
      bis-GMA composite has been presented. METHODS: Twenty New Zealand rabbits were
      divided into 4 groups: control and sham groups consisted of 2 and 6 rabbits,
      respectively. The "skull base defect" group (n = 6) underwent a unifrontal
      craniectomy and an iatrogenic ASBD followed by creating a dural defect to obtain
      a cerebrospinal fluid leak. Similar bony and dural defects were acquired in the
      "repair with bis-GMA based allograft" group (n = 6), but the bony defect was
      closed with bis-GMA-based allograft. RESULTS: All animals in the "skull base
      defect" group died in 3 weeks after surgery. There were no animal losses in the
      "repair with bis-GMA based allograft" group at the sixth month. Histologic
      evaluation revealed complete osteointegration of bis-GMA composite with
      surrounding bones. CONCLUSIONS: bis-GMA based allograft achieved a watertight
      repair of the ASBD. Histologic findings of this study showed that bis-GMA
      composite is a reliable material to be used in the closure of anterior skull base
      bony defects.

PMID- 24914758
TI  - A rare solitary neurofibroma of the frontal sinus.
AB  - Neurofibromas are common peripheral nerve sheath tumors related to Schwann cell's
      proliferation and are usually associated with neurofibromatosis type 1. Although
      solitary neurofibroma that occurs in the paranasal sinus is reported
      occasionally, neurofibroma located in the frontal sinus is extremely rare. Here,
      we report a case of a young woman who had a heterogeneous lesion in the left
      frontal sinus, eroding its anterior and posterior wall with signs of intracranial
      invasion. Postoperatively, results of the histologic examination confirmed the
      diagnosis of solitary neurofibroma. In conclusion, solitary neurofibroma should
      be considered in the differential diagnosis of frontal sinus masses. 

PMID- 24914757
TI  - Cholesteatoma of cerebellopontine angle presented as trigeminal neuralgia.
AB  - Cholesteatoma in the cerebellopontine angle presented as trigeminal neuralgia are
      not common. Between 2010 and 2013, 12 such patients were operated on in our
      department. Those patients included 8 females and 4 males with an average age of
      47.8 years. One patient was combined with the ipsilateral hemifacial spasm. Five
      patients had hypesthesia in the ipsilateral side of the face. During the surgery,
      a pearly sheen mass with boundary was found in the cerebellopontine angle, and
      the trigeminal root was buried in the tumor. The tumor was removed totally in all
      the cases. Afterwards, the trigeminal root was observed distorted in 5 and the
      offending vessel was finally distinguished in 9. Postoperatively, the symptoms
      were relieved in all the cases and no recurrence was found up to the 36-month
      period of follow-up. We believed that the etiology of secondary trigeminal
      neuralgia caused by cholesteatoma is still the neurovascular confliction; the
      only difference is that the offending vessel was pushed by the tumor instead of
      idiopathically. Sometimes, the offending artery may not be found after the tumor
      resection for it may have been transposed off while the tumor is being removed. 

PMID- 24914759
TI  - Ultrasonic aesthetic cranioplasty.
AB  - The management of frontal bone injury is an important issue, and inappropriate
      management of such injuries may give rise to serious complications. Piezosurgery
      is a technique used to perform safe and effective osteotomies using piezoelectric
      ultrasonic vibrations. This instrument allows a safe method for osteotomy of the
      cranial vault in close proximity to extremely injury-sensitive tissue such as the
      brain. After a wide review of the literature, the authors present this technical
      report, introduce the use of piezosurgery to perform a safe "slim-osteotomies"
      for treatment of posttraumatic frontal bone deformities, and suggest the use of
      this instrument for aesthetic recontouring of the craniofacial skeleton. 

PMID- 24914760
TI  - Unexpectedly high second-order nonlinear optical properties of simple Ru and Pt
      alkynyl complexes as an analytical springboard for NLO-active polymer films.
AB  - The unexpectedly high quadratic hyperpolarizability values of simple Ru and Pt
      alkynyl complexes have been measured by the EFISH technique, and this prompted us
      to investigate their potential as molecular building blocks for composite films
      with second harmonic generation properties. 

PMID- 24914762
TI  - The subjective burden of informal caregivers of persons with dementia: extended
      validation of the German language version of the Burden Scale for Family
      Caregivers (BSFC).
AB  - OBJECTIVE: In research as well as in the practice of caregiver counselling, the
      subjective burden of family caregivers is considered an important characteristic
      of home care. The objective of the present study was to provide an extended
      validation of the German language version of the Burden Scale for Family
      Caregivers (BSFC) published in 2001. METHODS: Extended validation was performed
      using medical, interview, and health insurance data of 351 informal caregivers
      and their relatives who had dementia. Cronbach's alpha was calculated to assess
      the internal consistency of the items, and an exploratory factor analysis was
      conducted to determine the structure of the BSFC. The discriminatory power and
      item difficulties of the 28 BSFC items were examined. Five research questions
      addressed construct validity. Question six addressed the BSFC score as a
      potential predictor of institutionalization at a follow-up time of 2.5 years
      (predictive validity). RESULTS: Exploratory factor analysis indicated that the
      BSFC had a single-factor structure. Cronbach's alpha for the total scale was
      0.93. A significant increase in the BSFC score was observed when the severity of
      cognitive impairment increased, persons with dementia showed disturbing
      behaviour, caregivers were diagnosed with depression, care requirements
      increased, or the family caregiver and the person with dementia lived together.
      Caregiver burden emerged as a significant predictor of institutionalization. The
      validity of the BSFC was confirmed by the results. CONCLUSION: The BSFC score
      allows for a valid assessment of the total caregiver burden in both research and
      practice. The BSFC is available for free in 20 languages ( http://www.caregiver
      burden.eu ).

PMID- 24914761
TI  - A polyvalent Clade B virus-like particle HIV vaccine combined with partially
      protective oral preexposure prophylaxis prevents simian-human immunodeficiency
      virus Infection in macaques and primes for virus-amplified immunity.
AB  - Vaccination and preexposure prophylaxis (PrEP) with antiretrovirals have shown
      only partial protection from HIV-1 infection in human trials. Oral Truvada
      (emtricitabine/tenofovir disoproxil fumarate) is FDA approved as PrEP but partial
      adherence reduces efficacy. If combined as biomedical preventions (CBP), an HIV
      vaccine could protect when PrEP adherence is low and PrEP could prevent vaccine
      breakthroughs. The efficacy of combining oral PrEP with an HIV vaccine has not
      been evaluated in humans. We determined the efficacy of combining a DNA/virus
      like particle (VLP) vaccine with partially effective intermittent PrEP in Indian
      rhesus macaques (RM). Eight RM received intramuscular inoculations of five DNA
      plasmids encoding four HIV-1 Clade B primary isolate Envs and SIVmac239 Gag (at
      weeks 0 and 4), followed by intramuscular and intranasal inoculations of
      homologous Gag VLPs and four Env VLPs (at weeks 12, 16, and 53). At week 61, we
      initiated weekly rectal exposures with heterologous SHIV162p3 (10 TCID50) along
      with oral Truvada (TDF, 22 mg/kg; FTC 20 mg/kg) dosing 2 h before and 22 h after
      each exposure. This PrEP regimen previously demonstrated 50% efficacy. Five
      controls (no vaccine, no PrEP) received weekly SHIV162p3. All controls were
      infected after a median of four exposures; the mean peak plasma viral load (VL)
      was 3.9*10(7) vRNA copies/ml. CBP protected seven of eight (87.5%) RM. The one
      infected CBP RM had a reduced peak VL of 8.8*10(5) copies/ml. SHIV exposures
      during PrEP amplified Gag and Env antibody titers in protected RM. These results
      suggest that combining oral PrEP with HIV vaccines could enhance protection
      against HIV-1 infection.

PMID- 24914763
TI  - Pregnane-type steroids from the Formosan soft coral Scleronephthya flexilis.
AB  - Three pregnane-type steroids, including a new metabolite, 3beta-methoxy-5,20
      pregnadiene (1) along with two known analogues, 3beta-acetoxy-5,20-pregnadiene
      (2) and 5alpha-pregna-1,20-dien-3-one (3) were isolated from the soft coral
      Scleronephthya flexilis. Standard spectroscopic techniques were used to determine
      the structure of new steroid 1. The absolute stereochemistry of steroid 2 was
      confirmed by X-ray diffraction analysis. Steroid 3 exhibited potent activity
      against MOLT-4 tumor cells. 

PMID- 24914765
TI  - Total protein extraction for metaproteomics analysis of methane producing
      biofilm: the effects of detergents.
AB  - Protein recovery is crucial for shotgun metaproteomics to study the in situ
      functionality of microbial populations from complex biofilms but still poorly
      addressed by far. To fill this knowledge gap, we systematically evaluated the
      sample preparation with extraction buffers comprising four detergents for the
      metaproteomics analysis of a terephthalate-degrading methanogenic biofilm using
      an on-line two-dimensional liquid chromatography tandem mass spectrometry (2D-LC
      MS/MS) system. Totally, 1018 non-repeated proteins were identified with the four
      treatments. On the whole, each treatment could recover the biofilm proteins with
      specific distributions of molecular weight, hydrophobicity, and isoelectric
      point. The extraction buffers containing zwitterionic and anionic detergents were
      found to harvest the proteins with better efficiency and quality, allowing
      identification up to 76.2% of total identified proteins with the LC-MS/MS
      analysis. According to the annotation with a relevant metagenomic database, we
      further observed different taxonomic profiles of bacterial and archaeal members
      and discriminable patterns of the functional expression among the extraction
      buffers used. Overall, the finding of the present study provides first insight to
      the effect of the detergents on the characteristics of extractable proteins from
      biofilm and the developed protocol combined with nano 2D-LC/MS/MS analysis can
      improve the metaproteomics studies on microbial functionality of biofilms in the
      wastewater treatment systems. 

PMID- 24914766
TI  - The cross talk between cGMP signal pathway and PKC in pulmonary endothelial cell
      angiogenesis.
AB  - Angiogenic proliferation of vascular endothelial cells is believed to play an
      important role in pulmonary vascular remodeling in pulmonary arterial
      hypertension. In the present study, we found that c-GMP (cyclic guanosine
      monophosphate) inhibited the proliferation and tube formation of pulmonary
      vascular endothelial cells induced by TGF-beta1, and that this process was
      reversed by PKG (protein kinase G) inhibitor and PKC (protein kinase C)
      inhibitor. In addition, small interfering RNA (siRNA) targeting ERK also reduced
      cellular proliferation. Furthermore, western blotting showed that cGMP down
      regulated the phosphorylation level of ERK1/2, which was reversed not only by PKG
      inhibitor but also by PKC inhibitor. Silencing different PKC isoforms showed that
      PKCDelta, PKCgamma and PKCalpha were involved in ERK phosphorylation, suggesting
      that PKC kinases have a permissive action. Three subtypes, PKCDelta, PKCgamma and
      PKCalpha are likely to be involved the phosphorylation suppression of ERK
      included cGMP. Taken together, these data suggest that ERK phosphorylation
      mediates the proliferation of pulmonary vascular endothelial cells, and PKC
      kinases have a permissive action in this process. 

PMID- 24914764
TI  - BMP-functionalised coatings to promote osteogenesis for orthopaedic implants.
AB  - The loss of bone integrity can significantly compromise the aesthetics and
      mobility of patients and can be treated using orthopaedic implants. Over the past
      decades; various orthopaedic implants; such as allografts; xenografts and
      synthetic materials; have been developed and widely used in clinical practice.
      However; most of these materials lack intrinsic osteoinductivity and thus cannot
      induce bone formation. Consequently; osteoinductive functionalisation of
      orthopaedic implants is needed to promote local osteogenesis and implant
      osteointegration. For this purpose; bone morphogenetic protein (BMP)
      functionalised coatings have proven to be a simple and effective strategy. In
      this review; we summarise the current knowledge and recent advances regarding BMP
      functionalised coatings for orthopaedic implants. 

PMID- 24914767
TI  - Direct interaction between selenoprotein P and tubulin.
AB  - Selenium (Se), an essential trace element for human health, mainly exerts its
      biological function via selenoproteins. Among the 25 selenoproteins identified in
      human, selenoprotein P (SelP) is the only one that contains multiple
      selenocysteines (Sec) in the sequence, and has been suggested to function as a Se
      transporter. Upon feeding a selenium-deficient diet, mice lacking SelP develop
      severe neurological dysfunction and exhibit widespread brainstem
      neurodegeneration, indicating an important role of SelP in normal brain function.
      To further elucidate the function of SelP in the brain, SelP was screened by the
      yeast two-hybrid system from a human fetal brain cDNA library for interactive
      proteins. Our results demonstrated that SelP interacts with tubulin, alpha 1a
      (TUBA1A). The interaction between SelP and tubulin was verified by fluorescence
      resonance energy transfer (FRET) and co-immunoprecipitation (co-IP) assays. We
      further found that SelP interacts with the C-terminus of tubulin by its His-rich
      domain, as demonstrated by FRET and Isothermal Titration Calorimetry (ITC)
      assays. The implications of the interaction between SelP and tubulin in the brain
      and in Alzheimer's disease are discussed. 

PMID- 24914768
TI  - The Rst-Neph family of cell adhesion molecules in Gallus gallus.
AB  - The Rst-Neph family comprises an evolutionarily conserved group of single-pass
      transmembrane glycoproteins that belong to the immunoglobulin superfamily and
      participate in a wide range of cell adhesion and recognition events in both
      vertebrates and invertebrates. In mammals and fish, three Rst-Neph members, named
      Neph1-3, are present. Besides being widely expressed in the embryo, particularly
      in the developing nervous system, they also contribute to the formation and
      integrity of the urine filtration apparatus in the slit diaphragm of kidney
      glomerular podocytes, where they form homodimers, as well as heterodimers with
      Nephrin, another immunoglobulin-like cell adhesion molecule. In mice, absence of
      Neph1 causes severe proteinuria, podocyte effacement and perinatal death, while
      in humans, a mutated form of Nephrin leads to congenital nephrotic syndrome of
      the Finnish type. Intriguingly, neither Nephrin nor Neph3 are present in birds,
      which nevertheless have typical vertebrate kidneys with mammalian-like slit
      diaphragms. These characteristics make, in principle, avian systems very helpful
      for understanding the evolution and functional significance of the complex
      interactions displayed by Rst-Neph proteins. To this end we have started a
      systematic study of chicken Neph embryonic and post-embryonic expression, both at
      mRNA and protein level. RT-qPCR mRNA quantification of the two Neph paralogues in
      adult tissues showed that both are expressed in heart, brain, and retina. Neph1
      is additionally present in kidney, liver, pancreas, lungs, and testicles, while
      Neph2 mRNA is barely detected in kidney, testicles, pancreas and absent in liver
      and lungs. In embryos, mRNA from both genes can already be detected at as early
      as stage HH14, and remain expressed until at least HH28. Finally, we used a
      specific antibody to examine the spatial dynamics and subcellular distribution of
      ggNeph2 between stages HH20-28, particularly in the mesonephros, dermomyotomes,
      developing heart, and retina.

PMID- 24914769
TI  - Relative Skeletal Effects in Different Sites of the Mandible With the Proximal
      Tibia During Ovariectomy and the Subsequent Estrogen Treatment.

PMID- 24914770
TI  - Nebulized medications for the treatment of dyspnea: a literature review.
AB  - BACKGROUND: Dyspnea significantly impacts quality of life and is one of the most
      common symptoms in advanced illness. Systemically-administered opioids and
      benzodiazepines have been the most studied and utilized pharmacologic treatments
      for refractory dyspnea. Less attention has been given to the use of these
      medications and others when nebulized. This article presents a review of the
      literature on the use of nebulized medications for the treatment of dyspnea
      related to cancer, chronic obstructive pulmonary disease, cystic fibrosis,
      interstitial lung disease, or experimentally-induced dyspnea. METHODS: A
      systematic review of peer-reviewed literature was conducted using Medline/PubMed,
      CINAHL, Cochrane, and Google Scholar. RESULTS: Thirty-nine publications were
      included in this review, including 17 high-quality clinical research studies, as
      defined by the GRADE system. The evidence for nebulized morphine remains mixed,
      whereas a potential benefit was suggested for nebulized furosemide,
      hydromorphone, and fentanyl. No conclusions could be drawn as to which disease
      population derived greatest benefit from nebulized medications, or whether jet or
      ultrasonic nebulizers were more effective for the delivery of these medications.
      CONCLUSIONS: More research is needed to assess the characteristics of specific
      diseases and the combination of different nebulizers and medications that may
      yield the greatest benefit, and to assess the safety and efficacy of the chronic
      use of nebulized opioids and furosemide. Until larger, longer-term studies are
      completed, the use of nebulized medications to treat dyspnea should be assessed
      on a case-by-case basis and may be considered if the hoped-for benefits outweigh
      potential harm.

PMID- 24914771
TI  - Moving towards patient-centered medicine for COPD management: multidimensional
      approaches versus phenotype-based medicine--a critical view.
AB  - For decades, chronic obstructive pulmonary disease (COPD) has been considered a
      relentlessly progressive disease in which the deterioration of lung function is
      associated with an increase in symptoms, interrupted only by periods of
      exacerbation. However, this paradigm of COPD severity based on FEV1 has been
      challenged by currently available evidence. So far, three main approaches, though
      with contradictory aspects, have been proposed in order to address the complexity
      of COPD as well as to develop appropriate diagnostic, prognostic and therapeutic
      strategies for the disease: 1) the use of independent, clinically relevant
      variables, 2) the use of multidimensional indices, and 3) disease approaches
      based on clinical phenotypes. Multivariable systems seem superior to FEV1 in
      predicting prognosis and defining disease severity. However, selection of
      variables available from current literature must be confronted with issues of
      medical practice. Future evidence will be needed to reveal their effective
      relationship with disease long-term prognosis and to demonstrate the most
      adequate cutoff values to be used in clinical settings. Multidimensional scores
      provide a good prognostic instrument for the identification of patients with a
      particular degree of disease severity. Clinical phenotyping can help clinicians
      identify the patients who respond to specific pharmacological interventions;
      however, there is some controversy about the phenotypes to select and their long
      term implications. Although these approaches are not perfect, they represent the
      first step towards patient-centered medicine for COPD. In the near-future, these
      different approaches should converge towards one new field to focus on the better
      management of COPD patients.

PMID- 24914772
TI  - Reaction between (Z)-arylchlorooximes and alpha-isocyanoacetamides: a procedure
      for the synthesis of aryl-alpha-ketoamide amides.
AB  - (Z)-Arylchlorooximes and alpha-isocyanoacetamides undergo a smooth reaction to
      produce 1,3-oxazol-2-oxime derivatives in good yields. Opening of the oxazole
      ring and deoximation reaction give a facile access to aryl-alpha-ketoamide
      amides, a class of privileged scaffolds in medicinal chemistry and important
      synthetic intermediates in organic chemistry. 

PMID- 24914773
TI  - The accuracy and precision of DXA for assessing body composition in team sport
      athletes.
AB  - This study determined the precision of pencil and fan beam dual-energy X-ray
      absorptiometry (DXA) devices for assessing body composition in professional
      Australian Football players. Thirty-six professional Australian Football players,
      in two groups (fan DXA, N = 22; pencil DXA, N = 25), underwent two consecutive
      DXA scans. A whole body phantom with known values for fat mass, bone mineral
      content and fat-free soft tissue mass was also used to validate each DXA device.
      Additionally, the criterion phantom was scanned 20 times by each DXA to assess
      reliability. Test-retest reliability of DXA anthropometric measures were derived
      from repeated fan and pencil DXA scans. Fat-free soft tissue mass and bone
      mineral content from both DXA units showed strong correlations with, and trivial
      differences to, the criterion phantom values. Fat mass from both DXA showed
      moderate correlations with criterion measures (pencil: r = 0.64; fan: r = 0.67)
      and moderate differences with the criterion value. The limits of agreement were
      similar for both fan beam DXA and pencil beam DXA (fan: fat-free soft tissue mass
      = -1650 +/- 179 g, fat mass = -357 +/- 316 g, bone mineral content = 289 +/- 122
      g; pencil: fat-free soft tissue mass = -1701 +/- 257 g, fat mass = -359 +/- 326
      g, bone mineral content = 177 +/- 117 g). DXA also showed excellent precision for
      bone mineral content (coefficient of variation (%CV) fan = 0.6%; pencil = 1.5%)
      and fat-free soft tissue mass (%CV fan = 0.3%; pencil = 0.5%) and acceptable
      reliability for fat measures (%CV fan: fat mass = 2.5%, percent body fat = 2.5%;
      pencil: fat mass = 5.9%, percent body fat = 5.7%). Both DXA provide precise
      measures of fat-free soft tissue mass and bone mineral content in lean Australian
      Football players. DXA-derived fat-free soft tissue mass and bone mineral content
      are suitable for assessing body composition in lean team sport athletes.

PMID- 24914774
TI  - Proteome-wide analysis and diel proteomic profiling of the cyanobacterium
      Arthrospira platensis PCC 8005.
AB  - The filamentous cyanobacterium Arthrospira platensis has a long history of use as
      a food supply and it has been used by the European Space Agency in the MELiSSA
      project, an artificial microecosystem which supports life during long-term manned
      space missions. This study assesses progress in the field of cyanobacterial
      shotgun proteomics and light/dark diurnal cycles by focusing on Arthrospira
      platensis. Several fractionation workflows including gel-free and gel-based
      protein/peptide fractionation procedures were used and combined with LC-MS/MS
      analysis, enabling the overall identification of 1306 proteins, which represents
      21% coverage of the theoretical proteome. A total of 30 proteins were found to be
      significantly differentially regulated under light/dark growth transition.
      Interestingly, most of the proteins showing differential abundance were related
      to photosynthesis, the Calvin cycle and translation processes. A novel aspect and
      major achievement of this work is the successful improvement of the
      cyanobacterial proteome coverage using a 3D LC-MS/MS approach, based on an
      immobilized metal affinity chromatography, a suitable tool that enabled us to
      eliminate the most abundant protein, the allophycocyanin. We also demonstrated
      that cell growth follows a light/dark cycle in A. platensis. This preliminary
      proteomic study has highlighted new characteristics of the Arthrospira platensis
      proteome in terms of diurnal regulation. 

PMID- 24914775
TI  - Preoperative mapping of the sensorimotor cortex: comparative assessment of task
      based and resting-state FMRI.
AB  - Resting state fMRI (rs-fMRI) has recently been considered as a possible
      complement or alternative to task-based fMRI (tb-fMRI) for presurgical mapping.
      However, evidence of its usefulness remains scant, because existing studies have
      investigated relatively small samples and focused primarily on qualitative
      evaluation. The aim of this study is to investigate the clinical usefulness of rs
      fMRI in the context of presurgical mapping of motor functions, and in particular
      to determine the degree of correspondence with tb-fMRI which, while not a gold
      standard, is commonly used in preoperative setting. A group of 13 patients with
      lesions close to the sensorimotor cortex underwent rs-fMRI and tb-fMRI to
      localize the hand, foot and mouth motor areas. We assessed quantitatively the
      degree of correspondence between multiple rs-fMRI analyses (independent-component
      and seed-based analyses) and tb-fMRI, with reference to sensitivity and
      specificity of rs-fMRI with respect to tb-fMRI, and centre-of-mass distances.
      Agreement with electro-cortical stimulation (ECS) was also investigated, and a
      traditional map thresholding approach based on agreement between two experienced
      operators was compared to an automatic threshold determination method. Rs-fMRI
      can localize the sensorimotor cortex successfully, providing anatomical
      specificity for hand, foot and mouth motor subregions, in particular with seed
      based analyses. Agreement with tb-fMRI was only partial and rs-fMRI tended to
      provide larger patterns of correlated activity. With respect to the ECS data
      available, rs-fMRI and tb-fMRI performed comparably, even though the shortest
      distance to stimulation points was observed for the latter. Notably, the results
      of both were on the whole robust to thresholding procedure. Localization
      performed by rs-fMRI is not equivalent to tb-fMRI, hence rs-fMRI cannot be
      considered as an outright replacement for tb-fMRI. Nevertheless, since there is
      significant agreement between the two techniques, rs-fMRI can be considered with
      caution as a potential alternative to tb-fMRI when patients are unable to perform
      the task. 

PMID- 24914776
TI  - Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under
      oxidative stress via reducing excitotoxicity.
AB  - Several lines of evidence demonstrate that oxidative stress is involved in the
      pathogenesis of neurodegenerative diseases, including Parkinson's disease. Potent
      antioxidants may therefore be effective in the treatment of such diseases.
      Cabergoline, a dopamine D2 receptor agonist and antiparkinson drug, has been
      studied using several cell types including mesencephalic neurons, and is
      recognized as a potent radical scavenger. Here, we examined whether cabergoline
      exerts neuroprotective effects against oxidative stress through a receptor
      mediated mechanism in cultured cortical neurons. We found that neuronal death
      induced by H2O2 exposure was inhibited by pretreatment with cabergoline, while
      this protective effect was eliminated in the presence of a dopamine D2 receptor
      inhibitor, spiperone. Activation of ERK1/2 by H2O2 was suppressed by cabergoline,
      and an ERK signaling pathway inhibitor, U0126, similarly protected cortical
      neurons from cell death. This suggested the ERK signaling pathway has a critical
      role in cabergoline-mediated neuroprotection. Furthermore, increased
      extracellular levels of glutamate induced by H2O2, which might contribute to ERK
      activation, were reduced by cabergoline, while inhibitors for NMDA receptor or L
      type Ca2+ channel demonstrated a survival effect against H2O2. Interestingly, we
      found that cabergoline increased expression levels of glutamate transporters such
      as EAAC1. Taken together, these results suggest that cabergoline has a protective
      effect on cortical neurons via a receptor-mediated mechanism including repression
      of ERK1/2 activation and extracellular glutamate accumulation induced by H2O2.

PMID- 24914777
TI  - Risk of lymphoma and solid cancer among patients with rheumatoid arthritis in a
      primary care setting.
AB  - BACKGROUND: Several studies have demonstrated an association between rheumatoid
      arthritis (RA) and lymphoproliferative malignancies, but pathogenic mechanisms
      remain unclear. We investigated 1) the risk of lymphoproliferative malignancies
      and solid tumors in adults with RA identified in primary care and 2) the possible
      mediating role of blood eosinophilia in the clonal evolution of cancer in these
      patients. METHODS: From the Copenhagen Primary Care Differential Count (CopDiff)
      Database, we identified 356,196 individuals with at least one differential cell
      count (DIFF) encompassing the eosinophil count between 2000-2007. From these, one
      DIFF was randomly chosen (the index DIFF). By linking to the Danish National
      Patient Register, we categorized the selected individuals according to known
      longstanding (>=3 years) or recent onset (<3 years) RA prior to the index DIFF.
      In addition, the cohort was stratified according to management in primary or
      secondary care. From the Danish Cancer Registry we ascertained malignancies
      within four years following the index DIFF. Using multivariable logistic
      regression, odds ratios (OR) were calculated and adjusted for sex, age, year,
      month, eosinophilia, comorbid conditions and C-reactive protein (CRP). RESULTS:
      921 patients had recent onset RA and 2,578 had longer disease duration. Seventy
      three percent of RA patients were managed in primary care. After adjustment for
      sex, age, year, and month, neither recent onset nor long-standing RA was
      associated with incident lymphoproliferative malignancies or solid cancers. These
      risk estimates did not change when eosinophilia, CRP, and comorbidities were
      included in the models. CONCLUSIONS: In this large cohort of patients with RA of
      short or long duration recruited from a primary care resource, RA was not
      associated with an increased risk of lymphoproliferative or solid cancers during
      4 years of follow-up, when the models were adjusted for confounders. Blood
      eosinophilia could not be identified as a mediator of cancer development in the
      present setting.

PMID- 24914778
TI  - Exploring novel bands and key index for evaluating leaf equivalent water
      thickness in wheat using hyperspectra influenced by nitrogen.
AB  - Leaf equivalent water thickness (LEWT) is an important indicator of crop water
      status. Effectively monitoring the water status of wheat under different nitrogen
      treatments is important for effective water management in precision agriculture.
      Trends in the variation of LEWT in wheat plants during plant growth were analyzed
      based on field experiments in which wheat plants under various water and nitrogen
      treatments in two consecutive growing seasons. Two-band spectral indices
      [normalized difference spectral indices (NDSI), ratio spectral indices (RSI),
      different spectral indices (DSI)], and then three-band spectral indices were
      established based on the best two-band spectral index within the range of 350
      2500 nm to reduce the noise caused by nitrogen and saturation. Then, optimal
      spectral indices were selected to construct models of LEWT monitoring in wheat.
      The results showed that the two-band spectral index NDSI(R1204, R1318) could be
      used for LEWT monitoring throughout the wheat growth season, but the model
      performed differently before and after anthesis. Therefore, further two-band
      spectral indices NDSIb(R1445, R487), NDSIa(R1714, R1395), and NDSI(R1429, R416),
      were constructed for the two developmental phases, with NDSI(R1429, R416)
      considered to be the best index. Finally, a three-band index (R1429-R416
      R1865)/(R1429+R416+R1865), which was superior for monitoring LEWT and reducing
      the noise caused by nitrogen, was formed on the best two-band spectral index
      NDSI(R1429, R416) by adding the 1,865 nm wavelenght as the third band. This
      produced more uniformity and stable performance compared with the two-band
      spectral indices in the LEWT model. The results are of technical significance for
      monitoring the water status of wheat under different nitrogen treatments in
      precision agriculture. 

PMID- 24914779
TI  - Pregabalin versus placebo in postoperative pain relief of patients' status post
      photorefractive keratectomy: a double-masked, randomized, prospective study.
AB  - PURPOSE: Gabapentinoids are currently being used anecdotally for postoperative
      pain following photorefractive keratectomy (PRK) despite the lack of evidence.
      The purpose of this study is to evaluate the effectiveness of pregabalin in
      mitigating pain after PRK compared to the standard of care. METHODS: One hundred
      thirty-five patients scheduled for PRK at the Joint Warfighter Refractive Surgery
      Center in San Antonio, Texas were randomized to receive either oral pregabalin 75
      mg twice daily for 5 days or placebo, in addition to the standard pain care
      regimen. RESULTS: There was no statistically significant difference in the
      primary outcome of 10% improvement in subjective pain scores between the
      treatment and placebo groups at any point during the postoperative period, but
      there was a trend for lower subjective pain scores in the pregabalin group. There
      was a statistically significant difference in the frequency of rescue pain
      medications used on postoperative days 1 and 2. The pregabalin group required an
      average of 1.7 doses of rescue medications on postoperative day 1 versus 2.4
      doses in the placebo group, and 1.7 doses versus 2.6 doses on postoperative day 2
      (P<0.05). CONCLUSIONS: This study demonstrates that pregabalin may provide an
      alternative or add-on option to standard narcotics for pain relief after PRK.

PMID- 24914780
TI  - Modeling evolution of resistance of sugarcane borer (Lepidoptera: Crambidae) to
      transgenic Bt corn.
AB  - Diatraea saccharalis (F.) (Lepidoptera: Crambidae) is a target pest of transgenic
      corn expressing Bacillus thuringiensis (Bt) protein, and the first evidence of
      resistance by D. saccharalis to Cry1Ab corn was detected in a field population in
      northeast Louisiana in 2004. We used a model of population dynamics and genetics
      of D. saccharalis to 1) study the effect of interfield dispersal, the first date
      that larvae enter diapause for overwintering, toxin mortality, the proportion of
      non-Bt corn in the corn patch, and the area of a crop patch on Bt resistance
      evolution; and 2) to identify gaps in empirical knowledge for managing D.
      saccharalis resistance to Bt corn. Increasing, the proportion of corn refuge did
      not always improve the durability of Bt corn if the landscape also contained
      sugarcane, sorghum, or rice. In the landscape, which consisted of 90% corn area,
      5% sorghum area, and 5% rice area, the durability of single-protein Bt corn was
      40 yr when the proportion of corn refuge was 0.2 but 16 yr when the proportion of
      corn refuge was 0.5. The Bt resistance evolution was sensitive to a change (from
      Julian date 260 to 272) in the first date larvae enter diapause for overwintering
      and moth movement. In the landscapes with Bt corn, non-Bt corn, sugarcane,
      sorghum, and rice, the evolution of Bt resistance accelerated when larvae entered
      diapause for overwintering early. Intermediate rates of moth movement delayed
      evolution of resistance more than either extremely low or high rates. This study
      suggested that heterogeneity in the agrolandscapes may complicate the strategy
      for managing Bt resistance in D. saccharalis, and designing a Bt resistance
      management strategy for D. saccharalis is challenging because of a lack of
      empirical data about overwintering and moth movement. 

PMID- 24914782
TI  - Basic research: urethral sphincter regeneration using stem cells from amniotic
      fluid.

PMID- 24914781
TI  - Variation at genes influencing facial morphology are not associated with
      developmental imprecision in human faces.
AB  - Facial asymmetries are commonly used as a proxy for human developmental
      imprecision resulting from inbreeding, and thus reduced genetic heterozygosity.
      Several environmental factors influence human facial asymmetry (e.g., health
      care, parasites), but the generalizability of findings on genetic stressors has
      been limited in humans by sample characteristics (island populations, endogamy)
      and indirect genetic assessment (inference from pedigrees). In a sample of 3215
      adult humans from the Rotterdam Study, we therefore studied the relationship of
      facial asymmetry, estimated from nine mid-facial landmarks, with genetic
      variation at 102 single nucleotide polymorphism (SNP) loci recently associated
      with facial shape variation. We further tested whether the degree of individual
      heterozygosity is negatively correlated with facial asymmetry. An ANOVA tree
      regression did not identify any SNP relating to either fluctuating asymmetry or
      total asymmetry. In a general linear model, only age and sex--but neither
      heterozygosity nor any SNP previously reported to covary with facial shape--was
      significantly related to total or fluctuating asymmetry of the midface. Our study
      does not corroborate the common assumption in evolutionary and behavioral biology
      that morphological asymmetries reflect heterozygosity. Our results, however, may
      be affected by a relatively small degree of inbreeding, a relatively stable
      environment, and an advanced age in the Rotterdam sample. Further large-scale
      genetic studies, including gene expression studies, are necessary to validate the
      genetic and developmental origin of morphological asymmetries.

PMID- 24914783
TI  - Prostate cancer: metformin--the new wonder drug?

PMID- 24914784
TI  - Surgery: retroperitoneoscopic partial nephrectomy: practice is key.

PMID- 24914786
TI  - Conservative management of vestibular schwannoma: expectations based on the
      length of the observation period.
AB  - OBJECTIVE: Evaluate long-term prevalence of tumor growth and need for further
      treatment in patients with a vestibular schwannoma treated with conservative
      management. STUDY DESIGN: Retrospective chart review. SETTING: Private
      neurotologic tertiary referral center. PATIENTS: Vestibular schwannoma patients
      undergoing conservative management and previously studied (N = 114). Mean time to
      last magnetic resonance imaging was 4.8 years and to last follow-up was 6.4 years
      (maximum, 18.5 yr). INTERVENTION: Serial gadolinium-enhanced magnetic resonance
      imaging with size measurement. MAIN OUTCOME MEASURES: Change in maximum tumor
      dimension of 2 mm or higher (growth), further treatment, audiologic measures-pure
      tone average, word recognition, AAO-HNS (American Academy of Otolaryngology-Head
      and Neck Surgery) hearing class. RESULTS: Thirty-eight percent of tumors
      demonstrated growth; an average of 6.5 mm (SD, 3.8) at a mean rate of 3.1 mm per
      year. Of patients with no growth at 1 year or less, 20% grew by last follow-up.
      Overall, 31% had further treatment after a mean of 3.8 years (SD, 3.5; maximum,
      18.5 yr). Of those followed for 5 to 10 years, 18% eventually had further
      treatment. Only 56% of growing tumors had further treatment by last follow-up;
      14.8% with nongrowing tumors also had further treatment. Pure-tone average
      declined more in tumors that grew (mean Delta = 28.8 dB) than those that did not
      (mean Delta = 16.5 dB) (p <= 0.025), but there was no correlation between the
      amount of change in hearing and in the size of the tumor. Of patients with an
      initial AAO-HNS hearing Class A, 85.7% retained serviceable hearing. CONCLUSION:
      For patients electing an observation approach to treatment of vestibular
      schwannoma, about 31% may eventually undergo further treatment. Of those followed
      for 5 to 10 years, 18% eventually had further treatment. However, some patients
      are followed with radiologic evaluations for many years without necessity for
      further treatment.

PMID- 24914785
TI  - Protozoan ALKBH8 oxygenases display both DNA repair and tRNA modification
      activities.
AB  - The ALKBH family of Fe(II) and 2-oxoglutarate dependent oxygenases comprises
      enzymes that display sequence homology to AlkB from E. coli, a DNA repair enzyme
      that uses an oxidative mechanism to dealkylate methyl and etheno adducts on the
      nucleobases. Humans have nine different ALKBH proteins, ALKBH1-8 and FTO.
      Mammalian and plant ALKBH8 are tRNA hydroxylases targeting 5
      methoxycarbonylmethyl-modified uridine (mcm5U) at the wobble position of
      tRNAGly(UCC). In contrast, the genomes of some bacteria encode a protein with
      strong sequence homology to ALKBH8, and robust DNA repair activity was previously
      demonstrated for one such protein. To further explore this apparent functional
      duality of the ALKBH8 proteins, we have here enzymatically characterized a panel
      of such proteins, originating from bacteria, protozoa and mimivirus. All the
      enzymes showed DNA repair activity in vitro, but, interestingly, two protozoan
      ALKBH8s also catalyzed wobble uridine modification of tRNA, thus displaying a
      dual in vitro activity. Also, we found the modification status of tRNAGly(UCC) to
      be unaltered in an ALKBH8 deficient mutant of Agrobacterium tumefaciens,
      indicating that bacterial ALKBH8s have a function different from that of their
      eukaryotic counterparts. The present study provides new insights on the function
      and evolution of the ALKBH8 family of proteins. 

PMID- 24914787
TI  - Comparison of traditional histology and TSLIM optical sectioning of human
      temporal bones.
AB  - HYPOTHESIS: Thin-sheet laser imaging microscopy (TSLIM) optical sectioning can be
      used to assess temporal bone soft tissue morphology before celloidin sectioning.
      BACKGROUND: Traditional human temporal bone (TB) celloidin embedding and
      sectioning is a lengthy and involved process. Although bone morphology can be
      assessed with microCT before traditional histology, soft tissue structures are
      difficult to resolve until after celloidin sectioning. A potential solution is
      TSLIM, a high-resolution, nondestructive optical sectioning technique first
      developed to image bone and soft tissue in animal cochleae. METHODS: Two temporal
      bones from 1 individual were used to evaluate TSLIM's capacity to image human
      temporal bones (bone and soft tissue) before traditional histology. The right TB
      was trimmed to the cochlea, prepared for and imaged with TSLIM, then processed
      for celloidin sectioning. The left TB, serving as a control, was directly
      prepared for traditional celloidin sectioning. RESULTS: TSLIM imaging of the
      right TB showed adequate resolution of all major tissue structures but barely
      resolved cells. Celloidin sections produced from the TSLIM-imaged right TB were
      equivalent in cytologic detail to those from the traditionally prepared left TB.
      TSLIM 3-dimensional (3D) reconstructions were superior to those obtained from
      celloidin sections because TSLIM produced many more sections that were without
      mechanical sectioning artifacts or alignment issues. CONCLUSION: TSLIM processing
      disturbs neither gross nor detailed morphology and integrates well with celloidin
      histology, making it an ideal method to image soft tissue before celloidin
      sectioning.

PMID- 24914788
TI  - Sudden Sensorineural Hearing Loss Associated With Intralabyrinthine Hemorrhage.

PMID- 24914790
TI  - Ectopic meningioma (hamartoma) of the middle ear: a challenging case in frozen
      section.

PMID- 24914791
TI  - Extra-Axial Ependymoma Presenting as a Cerebellopontine Angle Mass.

PMID- 24914789
TI  - Osteoradionecrosis of the temporal bone: a case series.
AB  - OBJECTIVE: To study osteoradionecrosis (ORN) of the temporal bone. STUDY DESIGN:
      Retrospective case review. SETTING: Academic medical center. PATIENTS: Patients
      were included who had previously undergone radiation to the head and neck and
      then developed exposed necrotic bone within the ear canal that persisted at least
      3 months. INTERVENTIONS: Patients were treated with a variety of modalities,
      including conservative therapy with antibiotic ear drops and in-office
      debridements, hyperbaric oxygen therapy, and surgery. MAIN OUTCOME MEASURES: To
      describe the presentation and management of patients with temporal bone
      osteoradionecrosis. RESULTS: Thirty-three patients with temporal bone
      osteoradionecrosis were included. The most common site of primary tumor was the
      parotid gland (n = 11), followed by the nasopharynx (n = 7). The time to
      development of ORN varied between 1 and 22 years, with mean of 7.9 years. The
      mean radiation dose was 62.6 Gy to the primary tumor, 53.1 Gy to the affected
      temporal bone, and 65.2 Gy to the affected tympanic bone. The most common
      symptoms of ORN were otorrhea (n = 15), hearing loss (n = 13), and otalgia (n =
      12). Fifteen patients had bacterial superinfection, most commonly Staphylococcus
      aureus (n = 9). Conservative therapy was successful at managing symptoms but not
      in eradicating exposed bone in most patients. Surgery was used for recalcitrant
      pain, infection, cholesteatoma, cranial neuropathies, and intracranial
      complications. CONCLUSION: Osteoradionecrosis is a rare complication of radiation
      to the temporal bone. Management should be aimed at relief of symptoms,
      eradication of superinfection, and treatment of other commonly present radiation
      effects like cholesteatoma and hearing loss.

PMID- 24914793
TI  - Cervical vestibular evoked myogenic potentials in cerebellar lesions.
AB  - INTRODUCTION: Reports about cervical vestibular evoked myogenic potentials
      (cVEMPs) in central nervous system lesions are scarce. Our experience with
      cerebellar lesions is still evolving, with only a few cases published. The
      purpose of this article is to present our cVEMP findings of 3 cases with
      cerebellar lesions. MATERIALS AND METHODS: cVEMPs were performed using unilateral
      120-dB peak SPL intensity 1 kHz tone air-conducted sound stimulation with
      contralateral masking noise, with recording from the tonically active
      sternocleidomastoid muscle. RESULTS: Brain MRI scans showed a small focal lesion
      in the right middle cerebellar peduncle in our first case, 2 foci in the right
      middle cerebellar peduncle and cerebellar hemisphere in our second case, and
      lesions in the right superior and inferior cerebellar peduncles near the fourth
      ventricle in our final case. All cVEMPs were normal. DISCUSSION: cVEMPs seem to
      be unaffected by at least certain cerebellar peduncle and hemispheric lesions.
      Although an abnormal cVEMP result may suggest noncerebellar dysfunction, further
      work is needed, as the lesions reported may not be interrupting the known
      cerebellovestibular pathways. Normal cVEMP responses may also or otherwise be due
      to affected vestibular nuclei influenced by the above cerebellar lesions not
      being part of the cVEMP pathway.

PMID- 24914794
TI  - Metastatic Breast Cancer Presenting as a Jugular Foramen Mass.

PMID- 24914795
TI  - Surveillance after resection of vestibular schwannoma: measurement techniques and
      predictors of growth.
AB  - OBJECTIVES: To compare different methods of measuring tumor growth after
      resection of vestibular schwannoma and to identify predictors of growth. STUDY
      DESIGN: Retrospective case review. SETTING: Tertiary referral center, inpatient
      surgery with ambulatory follow-up. PATIENTS: All patients who underwent
      vestibular schwannoma resection by the senior author from September 1991 to April
      2012 and had two or more postoperative MRI scans. INTERVENTIONS: Vestibular
      schwannoma resection. Measurement of tumor size and enhancement pattern on
      postoperative magnetic resonance imaging scans. MAIN OUTCOME MEASURES: Tumor size
      as measured in one (linear), two (planar), and three (volumetric) dimensions
      using standard radiology workstation tools versus time elapsed since surgical
      resection. RESULTS: Eighty-eight patients were included with mean follow-up of
      3.9 years. Linear measurement of tumor size was found to have modest correlation
      with planar and volumetric measurements. Excellent correlation was found between
      the planar and volumetric methods. Nodular enhancement increased risk for tumor
      growth (OR 6.25, p = 0.03 on planar analysis). If there was growth, tumors with
      nodular enhancement typically showed increase in size beginning 2 years
      postoperatively, whereas those with linear or no enhancement were typically
      stable in size through 5 years. Younger age and larger preoperative tumor size
      were also risk factors for growth (OR 0.9/p = 0.01 and OR 1.09/p = 0.02).
      CONCLUSION: Simple planar measurement is an efficient method that correlates well
      with the more time-consuming volumetric method. The major risk factor for tumor
      growth is nodular enhancement on a baseline scan, a finding that warrants annual
      MRI beginning 2 years postoperatively. Younger age and larger preoperative size
      minimally increased risk of growth.

PMID- 24914796
TI  - Cholesteatoma recidivism: comparison of three different surgical techniques.
AB  - OBJECTIVE: To compare cholesteatoma recidivism rates after exclusive transcanal
      technique (ETC), combined transcanal and mastoidal technique (TCM, both subsets
      of intact canal wall technique, ICW), and canal wall down surgery (CWD). STUDY
      DESIGN: Retrospective case review and clinical case study SETTING: Tertiary
      referral center. PATIENTS: 406 cholesteatoma surgeries (2007-2009), 116 ears in
      clinical re-examination at least 1 year postoperatively. INTERVENTION: Sequential
      cholesteatoma surgery with ETC, TCM, or CWD. MAIN OUTCOME MEASURES: Cholesteatoma
      recidivism, residual and recurrent disease, localization of recidivism, validity
      of clinical findings. RESULTS: Out of 406 patients, ETC was performed in 227
      (56%), TCM in 122 (30%), and CWD in 57 (14%) cases. Recidivism rates after ICW
      (15%) and CWD (16%) were almost similar. Recidivism was more frequent after ETC
      (11%) than after TCM (25%). Residuals were observed in 2% after ETC, 6.5% after
      TCM, and 7% after CWD. Incidence of recurrent disease was 9% for ETC, 18% for
      TCM, and 9% for CWD. Preferred localization of recidivism was the tympanic cavity
      after ETC (92%) and CWD (56%) and the mastoid cavity after TCM (53%). The
      clinical re-examination showed no further recidivistic disease. CONCLUSIONS:
      Sequential surgery is an effective and successful strategy in cholesteatoma
      eradication, providing a similar recidivism rate compared to following
      cholesteatoma retrograde and resection of the posterior canal wall. Lower
      recidivism after ETC was observed as a consequence of limited disease and the
      postoperative middle ear status determined the higher rate of recurrence after
      TCM. Therefore, the restricted visualization of the middle ear during ICW surgery
      does not increase the rate of recidivism, compared with CWD, as described in
      other studies. Cholesteatoma recidivism is mainly attributed to the surgeon's
      experience that outweighs the chosen strategy.

PMID- 24914797
TI  - The incudomalleolar articulation in Down syndrome (trisomy 21): a temporal bone
      study.
AB  - HYPOTHESIS: One reason for conductive hearing loss (HL) in patients with Down
      syndrome (DS) is structural anomalies in the incudomalleolar joint (IMJ) that
      impair sound transmission. BACKGROUND: The majority of hearing losses in patients
      with DS are conductive. One reason is the high incidence of inflammatory
      processes such as otitis media. However, in some patients, the middle ear seems
      to be normal. The assumption of structural disorders causing a HL is supported by
      a previous study revealing structural abnormalities of the incudostapedial joint
      (ISJ) in these patients. METHODS: In a retrospective analysis, histologic
      sections of the IMJ of 16 patients with DS were compared with 24 age- and sex
      matched subjects with normal middle ear ossicles. The length of 8 parameters of
      the IMJ were measured at 3 positions and compared between the 2 groups. RESULTS:
      Age (p = 0.318) and sex distribution (p = 1) for the DS group and the matched
      controls were comparable. The IMJs (p < 0.001) and the cartilage of patients with
      DS are significantly wider in most measurements compared with controls. However,
      the joint space is not significantly different in the 2 groups. CONCLUSION:
      Conductive HL might be caused by a significantly wider IMJ in patients with DS
      supporting the findings of a previous study reporting similar findings for the
      ISJ. The etiology of these findings is unclear. Patients with DS have a high
      prevalence of deficient collagen synthesis. Immunohistochemical analysis may be
      needed to investigate the collagen structure of the ISJ and IMJ in patients with
      DS.

PMID- 24914798
TI  - Analysis of the prevalence of and risk factors for tinnitus in a young
      population.
AB  - BACKGROUND: Tinnitus in children and adolescents is known to be as common as in
      adults. However, tinnitus in this young population is often overlooked, and a
      large population-based study designed to adjust for various risk factors for
      tinnitus is lacking. METHODS: A cross-sectional study was conducted using data
      from the Korea National Health and Nutrition Examination Survey, with 3047
      participants aged 12 to 19 years, from 2008 through 2011. We investigated the
      tinnitus prevalence by questionnaire and analyzed risk factors for tinnitus of
      three types: personal, otologic, and parental factors. RESULTS: The prevalence of
      tinnitus in the young population was 17.7%, although only 0.3% of subjects
      reported severe discomfort caused by tinnitus. The tinnitus prevalence increased
      with age (adjusted odds ratio [AOR], 1.087). Female gender (AOR, 1.401), sleeping
      less than 9 hours (sleep 7 or 8 h: AOR, 1.437; sleep 6 h or less: AOR, 1.737),
      noise exposure in other places (AOR, 6.395), and momentary noise exposure (AOR,
      5.504) increased the risk of tinnitus. Participants whose mother had a history of
      tinnitus showed higher AORs. However, high body mass index, alcohol consumption,
      stress, monthly household income, having an abnormal tympanic membrane,
      unilateral or bilateral hearing loss, noise exposure caused by earphone, and
      noise exposure in the workplace, all reported risk factors for tinnitus, showed
      no statistically significant difference. A tinnitus history in the father was
      also not associated with tinnitus in children. CONCLUSION: We believe that
      understanding the influences of these factors will help in preventing tinnitus.

PMID- 24914799
TI  - Magnetosome-containing bacteria living as symbionts of bivalves.
AB  - Bacteria containing magnetosomes (protein-bound nanoparticles of magnetite or
      greigite) are common to many sedimentary habitats, but have never been found
      before to live within another organism. Here, we show that octahedral inclusions
      in the extracellular symbionts of the marine bivalve Thyasira cf. gouldi contain
      iron, can exhibit magnetic contrast and are most likely magnetosomes. Based on
      16S rRNA sequence analysis, T. cf. gouldi symbionts group with symbiotic and free
      living sulfur-oxidizing, chemolithoautotrophic gammaproteobacteria, including the
      symbionts of other thyasirids. T. cf. gouldi symbionts occur both among the
      microvilli of gill epithelial cells and in sediments surrounding the bivalves,
      and are therefore facultative. We propose that free-living T. cf. gouldi
      symbionts use magnetotaxis as a means of locating the oxic-anoxic interface, an
      optimal microhabitat for chemolithoautotrophy. T. cf. gouldi could acquire their
      symbionts from near-burrow sediments (where oxic-anoxic interfaces likely develop
      due to the host's bioirrigating behavior) using their superextensile feet, which
      could transfer symbionts to gill surfaces upon retraction into the mantle cavity.
      Once associated with their host, however, symbionts need not maintain structures
      for magnetotaxis as the host makes oxygen and reduced sulfur available via
      bioirrigation and sulfur-mining behaviors. Indeed, we show that within the host,
      symbionts lose the integrity of their magnetosome chain (and possibly their
      flagellum). Symbionts are eventually endocytosed and digested in host epithelial
      cells, and magnetosomes accumulate in host cytoplasm. Both host and symbiont
      behaviors appear important to symbiosis establishment in thyasirids.

PMID- 24914802
TI  - Children's hospital charters revisited.

PMID- 24914800
TI  - Genomic insights into the uncultured genus 'Candidatus Magnetobacterium' in the
      phylum Nitrospirae.
AB  - Magnetotactic bacteria (MTB) of the genus 'Candidatus Magnetobacterium' in phylum
      Nitrospirae are of great interest because of the formation of hundreds of bullet
      shaped magnetite magnetosomes in multiple bundles of chains per cell. These
      bacteria are worldwide distributed in aquatic environments and have important
      roles in the biogeochemical cycles of iron and sulfur. However, except for a few
      short genomic fragments, no genome data are available for this ecologically
      important genus, and little is known about their metabolic capacity owing to the
      lack of pure cultures. Here we report the first draft genome sequence of 3.42 Mb
      from an uncultivated strain tentatively named 'Ca. Magnetobacterium casensis'
      isolated from Lake Miyun, China. The genome sequence indicates an autotrophic
      lifestyle using the Wood-Ljungdahl pathway for CO2 fixation, which has not been
      described in any previously known MTB or Nitrospirae organisms. Pathways involved
      in the denitrification, sulfur oxidation and sulfate reduction have been
      predicted, indicating its considerable capacity for adaptation to variable
      geochemical conditions and roles in local biogeochemical cycles. Moreover, we
      have identified a complete magnetosome gene island containing mam, mad and a set
      of novel genes (named as man genes) putatively responsible for the formation of
      bullet-shaped magnetite magnetosomes and the arrangement of multiple magnetosome
      chains. This first comprehensive genomic analysis sheds light on the physiology,
      ecology and biomineralization of the poorly understood 'Ca. Magnetobacterium'
      genus.

PMID- 24914803
TI  - Letter to the editor.

PMID- 24914804
TI  - A small-molecule targeting the microRNA binding domain of argonaute 2 improves
      the retinoic acid differentiation response of the acute promyelocytic leukemia
      cell line NB4.
AB  - Argonaute proteins are pivotal regulators of gene expression mediating miRNAs
      function. Modulating their activity would be extremely useful to elucidate the
      processes governing small-RNAs-guided gene silencing. We report the
      identification of a chemical compound able to compete with Argonaute 2 miRNAs
      binding, and we demonstrate that this functional inhibition determines effects
      similar to Argonaute 2 shRNA-mediated down-regulation, favoring granulocytic
      differentiation of the acute promyelocytic leukemia cell line NB4 in response to
      retinoic acid. 

PMID- 24914805
TI  - Intense photocurrent from Mo-doped TiO2 film with depletion layer array.
AB  - A novel bilayer structure of TiO2 film was found capable of yielding fairly
      strong photocurrent under visible light. The base layer was lightly doped with Mo
      and then etched by reactive ion beam, and was finally covered by an undoped TiO2
      surface layer. Because of Fermi level drop at the interface of the trenches, such
      a deposition-etching-redeposition process implanted an array of depletion layer
      into TiO2 film successfully. Microstructures, crystallite parameters, and the
      absorption property were investigated with scanning electron microscope, atomic
      force microscopy, X-ray diffraction, and ultraviolet-visible spectroscopy in
      order. Photocurrent density was collected on an electrochemical workstation under
      visible light. The results indicate that carrier collection probability near
      depletion layer was enhanced significantly owing to high parallel diffusivity.
      Under visible light, current density demonstrates a marked increase as etching
      depth grows. At an etching depth around 660 nm, photocurrent density achieved is
      56 times larger than TiO2 film. Depletion layer at vertical trench edges may have
      a much bigger universal value than anticipated for various doping cases of wide
      bandgap films. 

PMID- 24914801
TI  - Formins as effector proteins of Rho GTPases.
AB  - Formin proteins were recognized as effectors of Rho GTPases some 15 years ago.
      They contribute to different cellular actin cytoskeleton structures by their
      ability to polymerize straight actin filaments at the barbed end. While not all
      formins necessarily interact with Rho GTPases, a subgroup of mammalian formins,
      termed Diaphanous-related formins or DRFs, were shown to be activated by small
      GTPases of the Rho superfamily. DRFs are autoinhibited in the resting state by an
      N- to C-terminal interaction that renders the central actin polymerization domain
      inactive. Upon the interaction with a GTP-bound Rho, Rac, or Cdc42 GTPase, the C
      terminal autoregulation domain is displaced from its N-terminal recognition site
      and the formin becomes active to polymerize actin filaments. In this review we
      discuss the current knowledge on the structure, activation, and function of
      formin-GTPase interactions for the mammalian formin families Dia, Daam, FMNL, and
      FHOD. We describe both direct and indirect interactions of formins with GTPases,
      which lead to formin activation and cytoskeletal rearrangements. The multifaceted
      function of formins as effector proteins of Rho GTPases thus reflects the
      diversity of the actin cytoskeleton in cells. 

PMID- 24914806
TI  - Prognostic value of human apurinic/apyrimidinic endonuclease 1 (APE1) expression
      in breast cancer.
AB  - Human apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein for DNA
      base excision repair (BER) and redox regulation. The ability of cancer cells to
      recognize DNA damage and initiate DNA repair is an important mechanism for
      therapeutic resistance. Several recent studies have suggested that APE1
      expression levels and/or subcellular dysregulation may be used to indicate the
      sensitivity of tumors to radiotherapy or chemotherapy. In this study, we assessed
      the prognostic significance of APE1 and differences in APE1 expression levels
      according to breast cancer molecular subtypes. We analyzed formalin-fixed,
      paraffin-embedded tumor tissue sections from 243 cases diagnosed as invasive
      breast cancer at Ewha Womans University Medical Center between January 2003 and
      December 2008. Immunohistochemistry was performed and the nuclear level of APE1
      was scored by taking into account the percentage of positive cells. Medical
      records were reviewed to investigate clinicopathologic characteristics. We found
      that nuclear APE1 high-level expression (proportion >=50%) in breast cancer
      showed a tendency towards unfavorable prognosis regarding disease-free survival
      (p = 0.093). However, there was no significant difference in overall survival
      between low and high-level expression groups (p = 0.294). Interestingly, within
      the Ki-67 low-level expression group, APE1 low-level expression was significantly
      associated with poor overall survival (p = 0.007). A significant positive
      correlation was observed between APE1 nuclear expression and estrogen receptor
      status (75.7% vs. 59.7%, p = 0.022). Also, the luminal A subtype was the most
      commonly observed breast cancer subtype in the APE1 high-level expression group
      (61.6% vs. 45.2%, p = 0.000). This study suggests that APE1 expression may be
      associated with breast cancer prognosis. In particular, its role as a prognostic
      factor would be significant for breast cancers with a low Ki-67 proliferation
      index. It is proposed that nuclear APE1 may be a novel target in breast cancer
      with a low proliferation rate to obtain better outcome. 

PMID- 24914808
TI  - Reduced inflammatory phenotype in microglia derived from neonatal rat spinal cord
      versus brain.
AB  - Microglia are the primary immune cells of the central nervous system (CNS).
      Membrane bound sensors on their processes monitor the extracellular environment
      and respond to perturbations of the CNS such as injury or infection. Once
      activated, microglia play a crucial role in determining neuronal survival. Recent
      studies suggest that microglial functional response properties vary across
      different regions of the CNS. However, the activation profiles of microglia
      derived from the spinal cord have not been evaluated against brain microglia in
      vitro. Here, we studied the morphological properties and secretion of
      inflammatory and trophic effectors by microglia derived from the brain or spinal
      cord of neonatal rats under basal culture conditions and after activation with
      lipopolysaccharide (LPS). Our results demonstrate that spinal microglia assume a
      less inflammatory phenotype after LPS activation, with reduced release of the
      inflammatory effectors tumor necrosis factor alpha, interleukin-1 beta, and
      nitric oxide, a less amoeboid morphology, and reduced phagocytosis relative to
      brain-derived microglia. Phenotypic differences between brain and spinal
      microglia are an important consideration when evaluating anti-inflammatory or
      immunomodulatory therapies for brain versus spinal injury. 

PMID- 24914807
TI  - Early and moderate sensory stimulation exerts a protective effect on perilesion
      representations of somatosensory cortex after focal ischemic damage.
AB  - Previous studies have shown that intensive training within an early critical time
      window after focal cortical ischemia increases the area of damaged tissue and is
      detrimental to behavioral recovery. We postulated that moderate stimulation
      initiated soon after the lesion could have protective effects on peri-infarct
      cortical somatotopic representations. Therefore, we have assessed the effects of
      mild cutaneous stimulation delivered in an attention-demanding behavioral context
      on the functional organization of the perilesion somatosensory cortex using high
      density electrophysiological mapping. We compared the effects of 6-day training
      initiated on the 3rd day postlesion (early training; ET) to those of same
      duration training started on the 8th day (delayed training; DT). Our findings
      confirm previous work showing that the absence of training aggravates
      representational loss in the perilesion zone. In addition, ET was found to be
      sufficient to limit expansion of the ischemic lesion and reduce tissue loss, and
      substantially maintain the neuronal responsiveness to tactile stimulation,
      thereby preserving somatotopic map arrangement in the peri-infarct cortical
      territories. By contrast, DT did not prevent tissue loss and only partially
      reinstated lost representations in a use-dependent manner within the spared peri
      infarct cortical area. This study differentiates the effects of early versus
      delayed training on perilesion tissue and cortical map reorganization, and
      underscores the neuroprotective influence of mild rehabilitative stimulation on
      neuronal response properties in the peri-infarct cortex during an early critical
      period. 

PMID- 24914809
TI  - Multi-country estimate of different manifestations of aspergillosis in cystic
      fibrosis.
AB  - Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA),
      Aspergillus sensitisation and Aspergillus bronchitis in CF. The relative
      frequencies of these entities have recently been ascertained in a large UK adult
      CF cohort. We have used this data to estimate the burden of aspergillosis and
      ABPA cases in adult CF patients in 30 countries reporting CF. National and
      international CF registry data was accessed and assessed for completeness and age
      distribution. Published proportions of ABPA (17.7%), Aspergillus sensitisation
      (14.6%) and Aspergillus bronchitis (30%) in CF were applied to those >18 years
      and compared with notified ABPA cases. Of the 76,201 estimated CF patients
      worldwide (not including India), 37,714 were >18 years. The proportion of adults
      to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults
      is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently
      recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared
      with estimated rates varies by country from 101% (France) to 14.5% (Greece),
      although genetic variation could account for genuine differences compared with
      the UK. Aspergillus bronchitis is not currently recognised or recorded in CF
      registries but there are an anticipated 10,988 adult cases. Aspergillus
      sensitisation, associated with increased bronchiectasis and reduced FEV1, affects
      an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together
      ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of
      the adult CF population. ABPA also occurs in children and teenagers and 984 cases
      were documented in registries. Diagnosed ABPA rates by age were available for the
      ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was <1% under
      4 years, and increased throughout childhood and adolescence, with marked
      variation between countries. Newly published diagnostic criteria and methods
      should facilitate better recognition of aspergillosis in CF, allowing better CF
      disease control. 

PMID- 24914811
TI  - Low medium pH value enhances anthocyanin accumulation in Malus crabapple leaves.
AB  - Anthocyanin is a critical factor involved in coloration of plant tissues, but the
      mechanism how medium pH values affect anthocyanin accumulation in woody plants is
      unknown. We analyzed anthocyanin composition and the expression of elements
      encoding anthocyanin and flavonols biosynthesis underlying different medium pH
      values by using three different leave color type cultivars. HPLC analysis
      demonstrated that high medium pH values treatment induced a dramatic decrease in
      the concentration of cyaniding in crabapple leaves. Conversely, the high medium
      pH values induced up-regulation of the content of flavones and flavonols,
      suggesting that low pH treatment-induced anthocyanin accumulation. Quantitative
      real time PCR experiment showed the expression level of anthocyanidin synthase
      (McANS) and uridine diphosphate glucose flavonoid 3-O-glucosyltransferase
      (McUFGT) was up-regulated by low pH values treatment, and high medium pH value
      treatment up-regulate the transcription level of flavonol synthase (McFLS).
      Meanwhile, several MYB TFs have been suggested in the regulation of pH responses.
      These results strongly indicate that the low pH treatment-induced anthocyanin
      accumulation is mediated by the variation of mRNA transcription of the
      anthocyanin biosynthetic genes. 

PMID- 24914810
TI  - Harvesting the promising fruits of genomics: applying genome sequencing
      technologies to crop breeding.
AB  - Next generation sequencing (NGS) technologies are being used to generate whole
      genome sequences for a wide range of crop species. When combined with precise
      phenotyping methods, these technologies provide a powerful and rapid tool for
      identifying the genetic basis of agriculturally important traits and for
      predicting the breeding value of individuals in a plant breeding population. Here
      we summarize current trends and future prospects for utilizing NGS-based
      technologies to develop crops with improved trait performance and increase the
      efficiency of modern plant breeding. It is our hope that the application of NGS
      technologies to plant breeding will help us to meet the challenge of feeding a
      growing world population.

PMID- 24914813
TI  - Titanium tattooing associated with zirconia implant abutments: a clinical report
      of two cases.
AB  - Worn particulate titanium abraded from a titanium dental implant that discolors
      the adjacent soft tissues has not previously been reported. Two cases of this
      gingival tissue "tattooing" are reported here. While the use of zirconia
      abutments in areas of high esthetic concern is widespread, the effects of
      particulate titanium being worn from the implant by the much harder abutment
      material and then taken up in the adjacent soft tissues should be considered as a
      potential complication and a consideration when selecting the type of abutment to
      be used. 

PMID- 24914812
TI  - Synergistic effects of 3D ECM and chemogradients on neurite outgrowth and
      guidance: a simple modeling and microfluidic framework.
AB  - During nervous system development, numerous cues within the extracellular matrix
      microenvironment (ECM) guide the growing neurites along specific pathways to
      reach their intended targets. Neurite motility is controlled by extracellular
      signal sensing through the growth cone at the neurite tip, including
      chemoattractive and repulsive cues. However, it is difficult to regenerate and
      restore neurite tracts, lost or degraded due to an injury or disease, in the
      adult central nervous system. Thus, it is important to evaluate the dynamic
      interplay between ECM and the concentration gradients of these cues, which would
      elicit robust neuritogenesis. Such information is critical in understanding the
      processes involved in developmental biology, and in developing high-fidelity
      neurite regenerative strategies post-injury, and in drug discovery and targeted
      therapeutics for neurodegenerative conditions. Here, we quantitatively
      investigated this relationship using a combination of mathematical modeling and
      in vitro experiments, and determined the synergistic role of guidance cues and
      ECM on neurite outgrowth and turning. Using a biomimetic microfluidic system, we
      have shown that cortical neurite outgrowth and turning under chemogradients (IGF
      1 or BDNF) within 3D scaffolds is highly regulated by the source concentration of
      the guidance cue and the physical characteristics of the scaffold. A mechanistic
      driven partial differential equation model of neurite outgrowth has been
      proposed, which could also be used prospectively as a predictive tool. The
      parameters for the chemotaxis term in the model are determined from the
      experimental data using our microfluidic assay. Resulting model simulations
      demonstrate how neurite outgrowth was critically influenced by the experimental
      variables, which was further supported by experimental data on cell-surface
      receptor expressions. The model results are in excellent agreement with the
      experimental findings. This integrated approach represents a framework for
      further elucidation of biological mechanisms underlying neuronal responses of
      specialized cell types, during various stages of development, and under healthy
      or diseased conditions. 

PMID- 24914814
TI  - Human gingival fibroblast (HGF-1) attachment and proliferation on several
      abutment materials with various colors.
AB  - PURPOSE: An implant abutment should be soft tissue-compatible and resistant to
      plaque accumulation, and it is preferable for an implant abutment to have color
      harmony with the surrounding tissues. This study aimed to compare the in vitro
      fibroblast cell attachment and proliferation on several abutment materials of
      different colors. MATERIALS AND METHODS: A total of 240 specimens in 6
      experimental groups were used: titanium alloy (SM [smooth machined]; gray),
      cobalt-chrome-molybdenum alloy (CCM; gray), titanium nitride-coated titanium
      (TiN; yellow), anodic-oxidized titanium (AO; dark pink), composite resin-coated
      titanium (R; white), and zirconia (Zr; white). The culture plate surface was
      employed as a control (C). The surface roughness (Sa), developed interfacial area
      ratio (Sdr), and water contact angle (WCA) were measured. The human gingival
      fibroblast (HGF-1) attachment and proliferation at the third and seventh days
      were observed. RESULTS: Sa values of all experimental groups were < 0.5 MUm. Sdr
      values were between 5% and 8%, except for the Zr group (0.06%). WCA of all groups
      was greater than 40 degrees. More HGF-1 cells attached on the surfaces of the SM,
      TiN, and Zr groups than the C group, and the least number of cells were observed
      on the CCM group (P < .001). On the third day of proliferation, the C group
      showed significantly greater proliferation than all experimental groups (P <
      .001). On the seventh day of proliferation, the TiN, AO, Zr, and C groups
      exhibited twice the number of cells compared to the rest of the groups (P <
      .001). CONCLUSION: Within the limitations of this study, zirconia abutments would
      be the best choice in the anterior region. Titanium nitride-coated titanium alloy
      abutments or anodic-oxidized titanium alloy abutments might also be good choices
      in areas of esthetic challenge or under high occlusal loads.

PMID- 24914815
TI  - Treatment of unstable thoracolumbar fractures through short segment pedicle screw
      fixation techniques using pedicle fixation at the level of the fracture: a finite
      element analysis.
AB  - OBJECTIVE: To compare the von Mises stresses of the internal fixation devices
      among different short segment pedicle screw fixation techniques to treat thoracic
      12 vertebral fractures, especially the mono-segment pedicle screw fixation and
      intermediate unilateral pedicle screw fixation techniques. METHODS: Finite
      element methods were utilised to investigate the biomechanical comparison of the
      four posterior short segment pedicle screw fixation techniques (S4+2: traditional
      short-segment 4 pedicle screw fixation [SPSF]; M4+2: mono-segment pedicle screw
      fixation; I6+2: intermediate bilateral pedicle screw fixation; and I5+2:
      intermediate unilateral pedicle screw fixation). RESULTS: The range of motion
      (ROM) in flexion, axial rotation, and lateral bending was the smallest in the
      I6+2 fixation model, followed by the I5+2 and S4+2 fixation models, but lateral
      bending was the largest in the M4+2 fixation model. The maximal stress of the
      upper pedicle screw is larger than the lower pedicle screw in S4+2 and M4+2. The
      largest maximal von Mises stress was observed in the upper pedicle screw in the
      S4+2 and M4+2 fixation models and in the lower pedicle screw in the I6+2 and I5+2
      fixation models. The values of the largest maximal von Mises stress of the
      pedicle screws and rods during all states of motion were 263.1 MPa and 304.5 MPa
      in the S4+2 fixation model, 291.6 MPa and 340.5 MPa in the M4+2 fixation model,
      182.9 MPa and 263.2 MPa in the I6+2 fixation model, and 269.3 MPa and 383.7 MPa
      in the I5+2 fixation model, respectively. Comparing the stress between different
      spinal loadings, the maximal von Mises stress of the implants were observed in
      flexion in all implanted models. CONCLUSION: Additional bilateral pedicle screws
      at the level of the fracture to SPSF may result in a stiffer construct and less
      von Mises stress for pedicle screws and rods. The largest maximal von Mises
      stress of the pedicle screws during all states of motion were observed in the
      mono-segment pedicle screw fixation technique.

PMID- 24914816
TI  - Epstein-Barr virus (EBV) infection in Chinese children: a retrospective study of
      age-specific prevalence.
AB  - BACKGROUND: Epstein-Barr Virus (EBV) is a globally prevalent herpesvirus
      associated with infectious mononucleosis and many malignancies. The survey on EBV
      prevalence appears to be important to study EBV-related diseases and determine
      when to administer prophylactic vaccine. The purpose of this retrospective study
      was to collect baseline information about the prevalence of EBV infection in
      Chinese children. METHODOLOGY/PRINCIPAL FINDING: We collected 1778 serum samples
      from healthy children aged 0 to 10, who were enrolled in conventional health and
      nutrition examinations without any EBV-related symptom in 2012 and 2013 in North
      China (n = 973) and South China (n = 805). We detected four EBV-specific
      antibodies, i.e., anti-VCA-IgG and IgM, anti-EBNA-IgG and anti-EA-IgG, by ELISA,
      representing all of the phases of EBV infection. The overall EBV seroprevalence
      in samples from North and South China were 80.78% and 79.38% respectively. The
      EBV seropositivity rates dropped slightly at age 2, and then increased gradually
      with age. The seroprevalence became stabilized at over 90% after age 8. In this
      study, the seroprevalence trends between North and South China showed no
      difference (P>0.05), and the trends of average antibody concentrations were
      similar as well (P>0.05). CONCLUSIONS/SIGNIFICANCE: EBV seroprevalence became
      more than 50% before age 3 in Chinese children, and exceed 90% after age 8. This
      study can be helpful to study the relationship between EBV and EBV-associated
      diseases, and supportive to EBV vaccine development and implementation.

PMID- 24914818
TI  - In silico characterization of the peptidome of the sea louse Caligus
      rogercresseyi (Crustacea, Copepoda).
AB  - Copepods of the order Siphonostomatoida are a major concern for commercial
      aquaculture as many farmed fish serve as hosts for these parasitic crustaceans.
      Caligus rogercresseyi, a member of the Siphonostomatoida, is a significant
      problem for salmonid aquaculture in the Southern Hemisphere, and as such, a
      search for methods for controlling infestations of it is ongoing. One possibility
      for biological control of this and other copepod ectoparasites is endocrine
      manipulation. However, little is known about the native endocrine signaling
      systems in these animals. As part of an ongoing effort to characterize crustacean
      ectoparasite peptidergic systems, the publicly accessible C. rogercresseyi
      transcriptome shotgun assembly (TSA) was mined for peptide-encoding transcripts.
      Using the identified TSA sequences, precursor proteins were deduced and their
      mature peptides predicted. Thirty-three peptide-encoding transcripts were
      identified within the Caligus TSA dataset, with the structures of 131 distinct
      peptides characterized from the deduced pre/preprohormones. The predicted
      peptides included isoforms of allatostatin A, allatostatin B, bursicon alpha,
      bursicon beta, corazonin, crustacean cardioactive peptide, crustacean
      hyperglycemic hormone, diuretic hormone 31, DXXRLamide, FLRFamide, FXGGXamide,
      GSEFLamide, insulin-like peptide (ILP), intocin, leucokinin, molt-inhibiting
      hormone, myosuppressin, neuroparsin, neuropeptide F (NPF), orcokinin and
      tachykinin-related peptide. The predicted ILPs are of particular note as they are
      the first members of this peptide family identified from a copepod. Similarly,
      the predicted complement of four distinct NPFs is larger than that known from
      other crustaceans. Taken collectively, these data greatly expand the known C.
      rogercresseyi peptidome and provide a foundation for initiating studies of
      peptidergic control in this species. 

PMID- 24914817
TI  - A 2-amino quinoline, 5-(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)-8
      dimethylcarbamyl-4,6-dithiaoctanoic acid, interacts with PfMDR1 and inhibits its
      drug transport in Plasmodium falciparum.
AB  - Malaria is a major disease in the tropics where chemotherapy remains the main
      mode of treatment and as such the rise and spread of drug-resistant malaria can
      lead to human tragedy. Two membrane transport proteins, PfMDR1 (Plasmodium
      falciparum multidrug resistance protein 1) and PfCRT (P. falciparum chloroquine
      resistance transporter), have been shown to cause resistance to several
      antimalarials. Both PfMDR1 and PfCRT are localized to the digestive vacuolar
      membrane and appear to regulate the transport of drugs and physiological
      metabolites. In this study we have used MK571, a 2-amino quinoline, to explore
      its interaction with PfMDR1 and PfCRT in chloroquine-sensitive and -resistant
      strains of P. falciparum. Our results show that chloroquine-resistant strains
      (e.g., K1, Dd2, and 7G8) are consistently more sensitive to MK571 than
      chloroquine-sensitive strains (e.g., 3D7, 106/1 and D10). This association,
      however, was not maintained with the chloroquine-resistant strain FCB which IC50
      value was similar to chloroquine-sensitive strains. Moreover, the susceptibility
      of chloroquine-sensitive and -resistant strains to MK571 does not correlate with
      mutated PfCRT, nor is it reversible with verapamil; but correlates with mutations
      in PfMDR1. Furthermore, MK571 appears to target the parasite's digestive vacuole
      (DV), as demonstrated by the ability of MK571 to: (1) block the accumulation of
      the fluorescent dye Fluo-4 AM, a PfMDR1 substrate, into the digestive vacuole;
      (2) reduce the transvacuolar pH gradient; and (3) inhibit the formation of beta
      hematin in vitro. Moreover, the presence of non-toxic concentrations of MK571
      sensitized both chloroquine-sensitive and -resistant parasites to mefloquine and
      halofantrine, likely by competing against PfMDR1-mediated sequestering of the
      drugs into the DV compartment and away from the drugs' cytosolic targets. Our
      data, nevertheless, found only a minimal decrease in MK571 IC50 value in FCB
      parasite which second pfmdr1 copy was inactivated via gene disruption. Taken
      together, the findings of this study suggest that MK571 interacts with native and
      mutant PfMDR1 and modulates the import of drugs or solutes into the parasite's DV
      and, as such, MK571 may be a useful tool in the characterization of PfMDR1 drug
      interactions and substrate specificity. 

PMID- 24914819
TI  - Prediction of molecular separation of polar-apolar mixtures on heterogeneous
      metal-organic frameworks: HKUST-1.
AB  - Due to the combination of metal ions and organic linkers and the presence of
      different types of cages and channels, metal-organic frameworks often possess a
      large structural and chemical heterogeneity, complicating their adsorption
      behavior, especially for polar-apolar adsorbate mixtures. By allocating isotherms
      to individual subunits in the structure, the ideal adsorbed solution theory
      (IAST) can be adjusted to cope with this heterogeneity. The binary adsorption of
      methanol and n-hexane on HKUST-1 is analyzed using this segregated IAST (SIAST)
      approach and offers a significant improvement over the standard IAST model
      predictions. It identifies the various HKUST-1 cages to have a pronounced polar
      or apolar adsorptive behavior. 

PMID- 24914820
TI  - Measurement properties of the late life disability index among individuals who
      use power wheelchairs as their primary means of mobility.
AB  - OBJECTIVE: To examine the reliability, validity, and factor structure of the Late
      Life Disability Instrument (LLDI) in individuals who use power wheelchairs as
      their primary means of mobility. DESIGN: A 4-week, test-retest study design.
      SETTING: Five Canadian cities. PARTICIPANTS: The validity sample included 115 new
      and experienced power mobility users, and the reliability sample included 85
      experienced users (N=115). These volunteer samples included individuals who were
      aged >=50 years and independently used power mobility as their primary means of
      mobility. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The LLDI measures
      participation in 2 dimensions of 16 life activities: frequency and perceived
      limitations. Validity measures included the Wheelchair Skills Test-power version,
      the Assistive Technology Outcomes Profile for Mobility, the Hospital Anxiety and
      Depression Scale, the Power Mobility Wheelchair Confidence Measure, and the Life
      Space Assessment. RESULTS: For the reliability sample, raw intraclass
      correlational coefficients for limitation and frequency dimension scores ranged
      from .855 (95% confidence interval .781-.905) to .883 (95% confidence interval,
      .822-.924), respectively. For the validity sample, scores on the LLDI were
      correlated as hypothesized with scores on validity measures. The factor structure
      that was identified with the original sample was not replicated among power
      wheelchair users. For LLDI frequency, exploratory factor analysis indicated that
      5 of the original 16 items did not perform similarly among power wheelchair
      users. For LLDI limitations, a 1-factor, rather than a 2-factor, solution was
      identified. CONCLUSIONS: The study provides evidence in support of the
      reliability and validity of the measure but suggests that the original subscale
      scores may not be applicable to power wheelchair users.

PMID- 24914822
TI  - Clostridium difficile infection in the hematopoietic unit: a meta-analysis of
      published studies.
AB  - Hematopoietic stem cell transplant (HSCT) recipients are at high risk of
      contracting Clostridium difficile infection (CDI). We systematically searched the
      PubMed and EMBASE databases through March 2014 and performed a random-effects
      meta-analysis to estimate the prevalence and trends of CDI over time. Among 48
      eligible articles that included 12,025 patients at risk, we estimated that 7.9%
      (95% confidence interval [CI], 6.5% to 9.5%) of HSCT patients are diagnosed with
      CDI during the peri-transplantation and late post-transplantation periods, an
      estimation that is relatively consistent across studies (tau(2) = .032).
      Prevalence of CDI is significantly higher among the 5120 allogeneic patients
      (9.3% [95% CI, 7.0% to 11.9%]), compared with the 4665 autologous patients (5.2%
      [95% CI, 3.8% to 6.9%]) (P = .02), and as many as 1 of 10 allogeneic transplant
      recipients are expected to be diagnosed with CDI compared with 1 of 20 autologous
      transplantation patients. However, this difference did not reach statistical
      significance when stratified data from the same centers were examined (P = .11).
      Importantly, we found an increasing trend of CDI diagnosis both worldwide (P =
      .02) and across studies conducted in North America (P = .03) over the last 34
      years. Notably, studies with a follow-up period that extended through the late
      post-transplantation period (after day +100) had a similar prevalence of CDI as
      those that followed patients only during the peri-transplantation period (up to
      day +100) (P = .94). In summary, CDI is common in the hematopoietic
      transplantation setting and the majority of infections occur in the peri
      transplantation period. The prevalence is almost 9-times higher than that
      reported among all hospital stays, with an increasing trend over time. 

PMID- 24914821
TI  - Varicella-zoster reactivation after allogeneic stem cell transplantation without
      routine prophylaxis--the incidence remains high.
AB  - One-year prophylaxis with acyclovir has been shown to effectively prevent
      varicella-zoster virus (VZV) reactivation after allogeneic hematopoietic stem
      cell transplantation (HSCT) in a cohort that underwent transplantation in the
      beginning of the 2000s. Transplantation procedures have since changed
      considerably and reduced-intensity conditioning (RIC) is nowadays common. We
      investigated VZV reactivation without routine prophylaxis in a cohort of HSCT
      patients, 50% of whom had received RIC. The cumulative 2-year incidence of VZV
      reactivation was 20.7%. Risk factors in a multivariate analysis were treatment
      with mesenchymal stromal cells (relative hazard [RH], 1.65; confidence interval
      [CI], 1.07 to 2.54; P = .02), total body irradiation >=6 Gy (RH, 1.55; CI, 1.14
      to 2.13; P = .006), engraftment later than day 16 (RH, 1.46; CI, 1.07 to 2.00; P
      = .02), and age 0 to 19 years (RH, 1.68; CI, 1.21 to 2.35; P = .002). There was
      no difference in VZV reactivation between patients receiving myeloablative
      conditioning or RIC. VZV-related complications occurred in 29% of the patients
      with reactivation; most common were disseminated disease and postherpetic
      neuralgia. No single low-risk group for VZV reactivation could be identified. We
      conclude that VZV reactivation remains common after HSCT and carries a high
      complication rate, warranting prophylaxis. 

PMID- 24914824
TI  - Properties of triplet-excited [N]cycloparaphenylenes (N = 8-12): excitation
      energies lower than those of linear oligomers and polymers.
AB  - Cycloparaphenylenes (CPPs), a class of hoop-shaped conjugated macrocycles, have
      attracted the attention of researchers in various fields because of their
      interesting properties. Although their properties in the singlet-excited state
      have been reported, there is no systematic information on the triplet-excited
      state. In the present study, the properties of triplet-excited [n]CPP (n = 8-12,
      where n denotes the number of phenyl rings) were comprehensively investigated.
      The phosphorescence peak shifted to the shorter-wavelength side with increasing
      ring size of the CPPs, indicating smaller triplet energy for smaller CPPs. It was
      found that the triplet energy of a smaller CPP is even smaller than those of
      poly(p-phenylene)s, indicating that small hoop-shaped conjugated macrocycles are
      effective in realizing low-band gap materials. By applying laser flash
      photolysis, the Tn-T1 absorption spectra of CPPs were obtained, from which the
      size-dependence of energy levels of higher triplet states were also determined.
      Generation of singlet oxygen by the energy transfer from a triplet-excited CPP
      was confirmed. The generation yield became smaller with increasing size of the
      CPP in accordance with the triplet yield. From these observations, the size
      dependence of the deactivation pathways is explained. 

PMID- 24914823
TI  - Regionally specific expression of high-voltage-activated calcium channels in
      thalamic nuclei of epileptic and non-epileptic rats.
AB  - The polygenic origin of generalized absence epilepsy results in dysfunction of
      ion channels that allows the switch from physiological asynchronous to
      pathophysiological highly synchronous network activity. Evidence from rat and
      mouse models of absence epilepsy indicates that altered Ca(2+) channel activity
      contributes to cellular and network alterations that lead to seizure activity.
      Under physiological circumstances, high voltage-activated (HVA) Ca(2+) channels
      are important in determining the thalamic firing profile. Here, we investigated a
      possible contribution of HVA channels to the epileptic phenotype using a rodent
      genetic model of absence epilepsy. In this study, HVA Ca(2+) currents were
      recorded from neurons of three different thalamic nuclei that are involved in
      both sensory signal transmission and rhythmic-synchronized activity during
      epileptic spike-and-wave discharges (SWD), namely the dorsal part of the lateral
      geniculate nucleus (dLGN), the ventrobasal thalamic complex (VB) and the
      reticular thalamic nucleus (NRT) of epileptic Wistar Albino Glaxo rats from
      Rijswijk (WAG/Rij) and non-epileptic August Copenhagen Irish (ACI) rats. HVA
      Ca(2+) current densities in dLGN neurons were significantly increased in
      epileptic rats compared with non-epileptic controls while other thalamic regions
      revealed no differences between the strains. Application of specific channel
      blockers revealed that the increased current was carried by L-type Ca(2+)
      channels. Electrophysiological evidence of increased L-type current correlated
      with up-regulated mRNA and protein expression of a particular L-type channel,
      namely Cav1.3, in dLGN of epileptic rats. No significant changes were found for
      other HVA Ca(2+) channels. Moreover, pharmacological inactivation of L-type
      Ca(2+) channels results in altered firing profiles of thalamocortical relay (TC)
      neurons from non-epileptic rather than from epileptic rats. While HVA Ca(2+)
      channels influence tonic and burst firing in ACI and WAG/Rij differently, it is
      discussed that increased Cav1.3 expression may indirectly contribute to increased
      robustness of burst firing and thereby the epileptic phenotype of absence
      epilepsy.

PMID- 24914825
TI  - Bone hierarchical structure in three dimensions.
AB  - Bone is a complex hierarchically structured family of materials that includes a
      network of cells and their interconnected cell processes. New insights into the 3
      D structure of various bone materials (mainly rat and human lamellar bone and
      minipig fibrolamellar bone) were obtained using a focused ion beam electron
      microscope and the serial surface view method. These studies revealed the
      presence of two different materials, the major material being the well-known
      ordered arrays of mineralized collagen fibrils and associated macromolecules, and
      the minor component being a relatively disordered material composed of individual
      collagen fibrils with no preferred orientation, with crystals inside and possibly
      between fibrils, and extensive ground mass. Significantly, the canaliculi and
      their cell processes are confined within the disordered material. Here we present
      a new hierarchical scheme for several bone tissue types that incorporates these
      two materials. The new scheme updates the hierarchical scheme presented by Weiner
      and Wagner (1998). We discuss the structures at different hierarchical levels
      with the aim of obtaining further insights into structure-function-related
      questions, as well as defining some remaining unanswered questions. 

PMID- 24914826
TI  - Antibacterial activity and cytocompatibility of titanium oxide coating modified
      by iron ion implantation.
AB  - In this work, zero valent iron nanoparticles (Fezero-NPs) and iron oxide
      nanoparticles (Feox-NPs) were synthesized at the subsurface and surface regions
      of titanium oxide coatings (TOCs) by plasma immersion ion implantation. This
      novel Fe-NPs/TOC system showed negligible iron releasing, great electron storage
      capability and excellent cytocompatibility in vitro. Importantly, the system
      showed selective antibacterial ability which can kill Staphylococcus aureus under
      dark conditions but has no obvious antibacterial effect against Escherichia coli.
      Owing to a bipolar Schottky barrier between Fezero-NPs/TOC and Fezero-NPs/Feox
      NPs, electrons could be captured by the Fezero-NPs bounded at the subsurface
      region of the coating. This electron storage capability of the Fe-NPs/TOC system
      induced extracellular electron transportation and accumulation of adequate
      valence-band holes (h(+)) at the external side, which caused oxidation damage to
      S. aureus cells in the dark. No obvious biocide effect against E. coli resulted
      from lack of electron transfer ability between E. coli and substrate materials.
      This work may open up a novel and controlled strategy to design coatings of
      implants with antibacterial ability and cytocompatibility for medical
      applications. 

PMID- 24914827
TI  - Sustained delivery of latanoprost by thermosensitive chitosan-gelatin-based
      hydrogel for controlling ocular hypertension.
AB  - Glaucoma is an irreversible ocular disease that may lead to progressive visual
      field loss and eventually to blindness with inadequately controlled intraocular
      pressure (IOP). Latanoprost is one of the most potent ocular hypotensive
      compounds, the current first-line therapy in glaucoma. However, the daily
      instillation required for efficacy and undesirable side-effects are major causes
      of treatment adherence failure and persistence in glaucoma therapy. In the
      present study, we developed an injectable thermosensitive
      chitosan/gelatin/glycerol phosphate (C/G/GP) hydrogel as a sustained-release
      system of latanoprost for glaucoma treatment. The latanoprost-loaded C/G/GP
      hydrogel can gel within 1min at 37 degrees C. The results show a sustained
      release of latanoprost from C/G/GP hydrogel in vitro and in vivo. The latanoprost
      loaded C/G/GP hydrogel showed a good in vitro and in vivo biocompatibility. A
      rabbit model of glaucoma was established by intravitreal injection of
      triamcinolone acetonide. After a single subconjunctival injection of latanoprost
      loaded C/G/GP hydrogel, IOP was significantly decreased within 8days and then
      remained at a normal level. The results of the study suggest that latanoprost
      loaded C/G/GP hydrogel may have a potential application in glaucoma therapy. 

PMID- 24914828
TI  - Engineered N-cadherin and L1 biomimetic substrates concertedly promote neuronal
      differentiation, neurite extension and neuroprotection of human neural stem
      cells.
AB  - We investigated the design of neurotrophic biomaterial constructs for human
      neural stem cells, guided by neural developmental cues of N-cadherin and L1
      adhesion molecules. Polymer substrates fabricated either as two-dimensional (2-D)
      films or three-dimensional (3-D) microfibrous scaffolds were functionalized with
      fusion chimeras of N-cadherin-Fc alone and in combination with L1-Fc, and the
      effects on differentiation, neurite extension and survival of H9 human-embryonic
      stem-cell-derived neural stem cells (H9-NSCs) were quantified. Combinations of N
      cadherin and L1-Fc co-operatively enhanced neuronal differentiation profiles,
      indicating the critical nature of the two complementary developmental cues.
      Notably, substrates presenting low levels of N-cadherin-Fc concentrations,
      combined with proportionately higher L1-Fc concentration, most enhanced neurite
      outgrowth and the degree of MAP2+ and neurofilament-M+ H9-NSCs. Low N-cadherin-Fc
      alone promoted improved cell survival following oxidative stress, compared to
      higher concentrations of N-cadherin-Fc alone or combinations with L1-Fc.
      Pharmacological and antibody blockage studies revealed that substrates presenting
      low levels of N-cadherin are functionally competent so long as they elicit a
      threshold signal mediated by homophilic N-cadherin and fibroblast growth factor
      signaling. Overall, these studies highlight the ability of optimal combinations
      of N-cadherin and L1 to recapitulate a "neurotrophic" microenvironment that
      enhances human neural stem cell differentiation and neurite outgrowth.
      Additionally, 3-D fibrous scaffolds presenting low N-cadherin-Fc further enhanced
      the survival of H9-NSCs compared to equivalent 2-D films. This indicates that
      similar biofunctionalization approaches based on N-cadherin and L1 can be
      translated to 3-D "transplantable" scaffolds with enhanced neurotrophic
      behaviors. Thus, the insights from this study have fundamental and translational
      impacts for neural-stem-cell-based regenerative medicine. 

PMID- 24914829
TI  - Sustained delivery of cytarabine-loaded vesicular phospholipid gels for treatment
      of xenografted glioma.
AB  - This study described the development of vesicular phospholipid gels (VPGs) for
      sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma.
      Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like
      numerous vesicles tightly packing together under the freeze-fracture electron
      microscopy (FF-TEM), their release profiles displayed sustained drug release up
      to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara
      C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from
      the implantation site in brain tissue within 28 days. At the same time,
      fluorescence micrograph confirmed drug distribution in brain tissue visually.
      Furthermore, after single administration, Ara-C-loaded VPGs group significantly
      inhibited the U87-MG glioma growth in right flank in comparison with Ara-C
      solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid
      degradation from cytidine deaminase and sustained release of drug from Ara-C
      loaded VPGs could maintain the effective therapeutic levels for a long time
      around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of
      sustained release, high penetration capacity, nontoxicity and no shape
      restriction of the surgical cavity, are promising local delivery systems for post
      surgical sustained chemotherapy against glioma.

PMID- 24914830
TI  - Colloidal particles containing labeling agents and cyclodextrins for theranostic
      applications.
AB  - This review aims to give to the reader some new light on cyclodextrin (CD)-based
      theranostic agents in order to complete our recently published review dedicated
      to CD-particles conjugates in drug delivery systems (Zafar et al., 2014). CDs are
      biocompatible sugar-based macrocycles used in a wide range of biomedical
      applications. Here, we mainly focus on fundamental theranostic approaches
      combining the use of cyclodextrin molecules and colloidal particles as
      theranostic agents. The system's key features are discussed and a few recent
      pertinent applications are presented. CDs are used in order to enhance
      theranostic properties by providing apolar cavities for the encapsulation of
      hydrophobic moieties. Thus, CD molecules are used to enhance the loading capacity
      of particles by hosting active molecules. The relevance of CDs in enhancing the
      labeling properties of particles and the preparation of controlled drug release
      particles is also highlighted. 

PMID- 24914832
TI  - Mobility measures should be added to the National Early Warning Score (NEWS).

PMID- 24914831
TI  - The impact of partial resuscitation attempts on the reported outcomes of out-of
      hospital cardiac arrest in Victoria, Australia: implications for Utstein-style
      outcome reports.
AB  - BACKGROUND: Success rates from cardiopulmonary resuscitation (CPR) are often
      quantified by Utstein-style outcome reports in populations who receive an
      attempted resuscitation. In some cases, evidence of futility is ascertained after
      a partial resuscitation attempt has been administered, and these cases reduce the
      overall effectiveness of CPR. We examine the impact of partial resuscitation
      attempts on the reported outcomes of out-of-hospital cardiac arrest (OHCA) in
      Victoria, Australia. METHODS: Between 2002 and 2012, 34,849 adult OHCA cases of
      presumed cardiac aetiology were included from the Victorian Ambulance Cardiac
      Arrest Registry. Resuscitation attempts lasting <=10min in cases which died on
      scene were defined as a partial resuscitation. We used logistic regression to
      identify factors associated with a partial resuscitation attempt in the emergency
      medical service (EMS) treated population. Survival outcomes with and without
      partial resuscitations were compared across included years. RESULTS: The
      proportion of partial resuscitations in the overall EMS treated population
      increased significantly from 8.6% in 2002 to 18.8% in 2012 (p for trend<0.001),
      and were largely supported by documented evidence of irreversible death. Partial
      resuscitations were independently associated with older age, female gender,
      initial non-shockable rhythm, prolonged downtime, and lower skill level of EMS
      personnel. Selectively excluding partial resuscitations increased event survival
      by 7.6% (95% CI 4.1-11.2%), and survival to hospital discharge increased by 3.1%
      (95% CI 0.5-5.7%) in 2012 (p<0.001 for both). CONCLUSION: In our EMS system,
      evidence of futility was often identified after the commencement of a partial
      resuscitation attempt. Excluding these events from OHCA outcome reports may
      better reflect the overall effectiveness of CPR.

PMID- 24914833
TI  - Widely used track and trigger scores: are they ready for automation in practice?

PMID- 24914834
TI  - To be permissive or not to be, is it the question?

PMID- 24914835
TI  - Prostate cancer epidemiology.
AB  - OBJECTIVES: The aim of this study is to provide an evidence-based analysis of the
      epidemiological situation of prostate cancer today and its future perspectives.
      METHOD: A literature review on Medline has been made of the most relevant papers
      related to the epidemiology of prostate cancer and their etiological factors. We
      selected for review those manuscripts with the highest level of evidence.
      RESULTS: Prostate cancer is the second most common neoplasia in men worldwide.
      The increasing trend in the incidente counteracted by an overall decrease in
      mortality from this disease have made prostate cancer an important health problem
      because of its high prevalence. There are significant geographic differences in
      terms of incidence and mortality. Age, ethnicity and family history are risk
      factors demonstrated but there are other factors related to the environment that
      play an important role in the biology of prostate cancer and tumor genesis.
      CONCLUSIONS: In the last 20 years there has been a progressive increase in the
      global incidence of this disease probably secondary to a progressive aging
      population, the improvement in diagnostic techniques and a higher intensity
      screening of prostate cancer. Though mortality has been reduced prostate cancer
      is the sixth cause of cancer-specific death worldwide. The combination of genetic
      and environmental factors may explain the ethnic and geographical variations in
      the incidence and mortality from prostate cancer.

PMID- 24914836
TI  - Natural history of prostate cancer.
AB  - Prostatic cancer can be a silent tumor, with no symptoms remaining undetectable
      throughout life . But when it keeps growing, enough to produce symptoms such as
      bladder neck obstruction, invasion of adjacent organs or distant metastasis,
      curative treatment is usually impossible. Since PSA emerges, data shows a
      dramatic increasing in the diagnosis of prostatic cancer, specially low risk
      tumor. Since then, We are wondering which tumors are suitable to be treated and
      which ones remain asymptomatic without treatment. Analysing the natural history
      of prostate cancer, helps us to choose the best atitude treating the tumor, this
      subjet has been in constant discusion in the last decade. Our article consistes
      of a reviewing the main publications treating natural history of prostate cancer
      in prehyphen;and post-PSA era. The indicated studied suggest that most prostate
      tumors diagnosed today are low grade cancer, as a result with a low mortality.
      This conclusion shows us the importance of modifying the algorithm of treatment
      of these tumors. 

PMID- 24914837
TI  - [Overdiagnosis in prostate cancer].
AB  - Prostate cancer screening is an absolutely controversial topic and under debate.
      The points of view from which the problem is analyzed also influence this issue;
      patient, physician and Health Care authorities have different interests that most
      of the times are not comprehensively analyzed. Currently, no clinical guideline
      supports the performance of a population screening with active recruitment, but
      they do support the credible information to the man who desires its performance
      of potential benefits and risks (opportunistic screening), as well as its
      performance in certain risk groups. Nevertheless, what is inherent to any
      screening program is the overdiagnosis of clinically irrelevant disease, which in
      prostate cancer has been calculated around 50%, and that, from our point of view,
      gives cause to the correct implementation of active surveillance programs to
      tamponade the potential deleterious effects of active therapies of prostate
      cancer.

PMID- 24914838
TI  - [Pathological consideration of indolent and clinically non-significant prostate
      cancer definition].
AB  - INTRODUCTION: Serum PSA determination has provoked a great increase of prostatic
      biopsies and detection of neoplasias that passed inadvertent in the past. When
      these neoplasias are excised a non-negligible number of them have low biologic
      aggressiveness and may be considered as indolent or clinically non-significant,
      so that the possibility of conservative attitude is taken into consideration.
      OBJECTIVE: How to recognize clinically non-significant carcinomas is one of the
      main challenges and is based on clinical criteria, but mainly pathological. The
      objective of this review is to analyze the state of this issue. METHODS: We
      selected those articles reviewing the topic in a general view over the last ten
      years. RESULTS/CONCLUSIONS: Trying to be as specific as possible search criteria
      have been refined to Gleason grade with an increase of Gleason 4 patterns (all
      cribiform patterns). In cases with two separated foci of carcinoma in the same
      biopsy core, it has been proposed to include as neoplasia the non-tumoral tissue
      between them. Obviously, with this there is lower sensitivity and it entails that
      there is no unanimous agreement (or consensus) about how to establish the
      criteria of clinically non-significant carcinoma. Therefore, once again, it is
      completely mandatory that urologists and pathologists work together, and while no
      consensus is reached both must know perfectly the guidelines of the center they
      work in.

PMID- 24914839
TI  - Prevalence of prostate cancer across the globe: what can autopsy studies teach us
      about this peculiar disease?
AB  - Prostate cancer (PCa) represents a major public health burden in the western
      world. It is a peculiar disease as more men die with it than from it. Also
      interestingly, PCa was virtually unknown for centuries until the 20th century.
      Randomized trials on PCa screening have outlined the risks of over-diagnosis and
      over-treatment of latent cancers. Significant geographical differences in PCa
      incidence and mortality exist, being supposedly low among Asian men compared to
      Caucasians. In some areas like Korea and Japan, changes have been observed that
      cannot be explained easily by changing diagnostic procedures and increases in
      mortality may be due to lifestyles and dietary changes. We have recently studied
      and compared the prevalence of PCa in Caucasian (CAU) from Moscow, Russia and
      Asian (ASI) men from Tokyo, Japan. We chose a specific Cau population in Russia
      with little sun exposure and high fat diet but without widespread PSA screening.
      Autopsy data in western countries (North America and Europe) would have been
      heavily contaminated due to opportunistic PSA screening. Screening in Asi men in
      Japan is uncommon. Prostates were removed en-block with the seminal vesicles
      within 24 hours of death and analyzed in toto (perpendicular sections at 4 mm
      intervals) by an experienced uro-pathologist in Toronto. PCa was found on autopsy
      in a similar proportion of Russian Caucasian and Japanese men. Over 50% of
      cancers are Gleason >=7 in Japanese and nearly 25% in Russian Caucasian men
      raising questions about 1) previous assumptions related to Asian PCa and 2) the
      notion of significant vs. insignificant cancers. Autopsy studies are key to
      improve our understanding of this very curious cancer.

PMID- 24914840
TI  - Optimization of prostate biopsy in patients considered for active surveillance.
      The role of the confirmatory biopsy and transperineal techniques.
AB  - OBJECTIVES: To review the pathological criteria used to select patients for
      active surveillance, the optimization of biopsies and the role of confirmatory
      biopsy and of the transperineal approach. METHODS: A bibliographic revision of
      the last years about active surveillance in prostate cancer as well as prostate
      biopsy, optimal rebiopsy protocols and transperineal approach has been carried
      out. RESULTS: Misclassification of insignificant disease based on pathological
      criteria of the first standard biopsy range from 20% to 30% of men. It is likely
      that many patients who ultimately progress on active surveillance had at the time
      of diagnosis more advanced disease that was missed by transrectal ultrasound
      (TRUS) biopsy. This is the main cause of progression on initial follow-up biopsy
      within 1 year of starting active surveillance. Although the role of immediate
      prostate rebiopsy after the diagnosis of low-risk prostate cancer and has not
      been well described, repeat biopsy before the initiation of AS performed shortly
      after diagnosis (6 months) identifies most patients who harbor high grade or more
      extensive cancers that may not be appropriate for a surveillance strategy.
      CONCLUSIONS: PSA, PSAD, and number of cores at initial diagnosis are not helpful
      in predicting misclassification of AS eligibility. The role of MRI for AS remains
      unclear and the technique of MRI/US fusion biopsy still lacks consensus on a
      standardized procedure. Patients considering active surveillance should undergo
      immediate confirmatory biopsy within 6 months to decrease the risk of
      substantially underestimating cancer size and grade, even in patients with strict
      criteria in the initial biopsy and subsequently, to better assess the risk of
      progression. In this way, most protocols of AS recommend performing volume-based
      biopsies in the confirmatory procedure. Perhaps, an extensive transperineal
      template-guided mapping biopsy (TTMB) procedure could more accurately identify
      those men with occult significant disease. Due to confirmatory biopsy identifies
      a patient group that is unlikely to progress during the first 5 to 10 years of AS
      the need of intensive biopsy schedule during follow-up of patients undergoing
      active surveillance might be reduced.

PMID- 24914841
TI  - [Selection criteria and nomograms for active surveillance in prostate cancer].
AB  - In the present review we detail the more universally accepted selection criteria
      in the various protocols of active surveillance in prostate cancer; we also
      identify and classify twenty nomograms/predictive models useful for decision
      making in active surveillance for prostate cancer. These models are classified in
      accordance to their prediction (High grade prostate cancer in radical
      prostatectomy specimen [Gleason grade > 7], understaging on biopsy compared to
      prostatectomy specimen, pathological stage, indolent cancer or progression after
      expectant therapy). We also detail the predictive variables used in each model
      for estimations, their internal validation parameters, the samples used to
      generate them, and the external validations if they were done. Many of them are
      presented with their URL address, where they may be consulted on line, this
      making easier their implementation. Finally we expose our thoughts about the use
      of probability density functions as a useful tool for validation of these
      predictive models that help in the definition of cut points facilitating their
      clinical use and credibility. 

PMID- 24914842
TI  - Prostatectomy pathology findings in an active surveillance population.
AB  - OBJECTIVES: The difficulty in predicting indolent prostate cancer leads to the
      use of different inclusion criteria in an active surveillance (AS) program. This
      chapter presents the pathology findings of radical prostatectomy (RP) in patients
      whose disease meet criteria for AS, as well as of those who are operated during
      AS. METHODS: Two independent Medline searches were conducted, both of them with a
      double objective: pathological findingsin radical prostatectomy specimens of
      patients who could have been included in AS and pathological features of patients
      operated after an AS period. The following terms were used for the research:
      "prostaticneoplasm", "radical prostatectomy" and "active surveillance": "radical
      prostatectomy", "after", "following" and "active surveillance". Pathological
      findings in radical prostatectomy specimens, down staging and downgrading rates
      were recorded. Active surveillance length and reason for surgery was included
      when it was available. RESULTS: Depending on different AS inclusion criteria,
      clinical downgrading rate (pathological Gleason > 6) varied between 12.1 and 61%
      and clinical downstaging between 0-26%. Pathological Gleason score =8 was
      reported in 0-7.8% and there were anecdotal findings of seminal vesicle invasion
      or positive nodes. Overall, unfavorable pathology (Gleason >= 7 or stage >=
      pT3)was detected in 13.1-42.4%, based on different definitions. The criteria at
      John Hopkins were the strictest and had the lowest clinical downgrading and
      downstaging. On the other hand, the Memorial Sloan Kettering Cancer Center(MSKCC)
      criteria had the highest risk of unfavorable pathology but had the highest
      recruitment capacity. Indolent tumor was observed in 70-82.2% according to the
      current definition. The average duration in AS prior to surgery was 15-37 months.
      pT3 stage was seen in 7.7-36.7%, Gleason score 3+4 in 18.6-42.9%, Gleason score
      4+3 in 1.4-31.8%, Gleason score >7 in 0-10.3%, positive margins in 3-40.9%.
      Seminal vesicle invasion rate was extremely low (0-2.9%) as well as positive
      nodes (0-4.5%). CONCLUSIONS: Although there is a low risk of clinical downstaging
      and downgrading between patients who have being included in AS, it remains
      feasible. The probability of predicting an indolent tumor depends greatly on the
      quality of the prostate biopsy and/or the confirmatory biopsy. On the other hand,
      most patients who progress in an AS program can have a high probability of cure.
      We are still in the early stages of AS management in order to be able to predict
      the biological behavior and the cure rate of radical prostatectomy in patients
      after a long AS period.

PMID- 24914843
TI  - [Optimization of follow up in prostate cancer active surveillance].
AB  - OBJECTIVES: Prostate cancer is a highly prevalent disease but with reduced cause
      specific mortality. Active surveillance represents an alternative to postpone or
      avoid the potential sequelae derived from curative treatments in selected
      patients. The objective of this article is to review the diagnostic and follow-up
      methods for patients included in active surveillance programs. METHODS: We
      performed an exhaustive bibliographic review with the terms "Prostate cancer",
      "Active surveillance", "expectant management", including the greatest series
      published since 2007. CONCLUSIONS: Awaiting for genetic markers that help us to
      predict diagnosis and evolution of prostate cancer, PSA kinetics, digital rectal
      examination and repeated biopsies continue being the inclusion and follow up
      criteria for patients in active surveillance programs. Emerging complementary
      tests such as multi parametric MRI, PCA3 and Phi seem to add specificity to the
      existing clinical criteria. The reduced number of patients included, the limited
      follow up and the great disparity of inclusion and follow up criteria between
      different groups make the implementation of consensus guidelines that could help
      a more widespread application of this alternative difficult.

PMID- 24914844
TI  - [Results of active surveillance in low and intermediate risk prostate cancer].
AB  - In this article we review the most significant published papers on active
      surveillance in prostate cancer and present the results of our case series. We
      used as main response variables the percentage of patients remaining in
      surveillance and the oncological results presented as global, cancer specific and
      metastasis free survivals. Globally, in published series 71.2% of patients
      included in active surveillance programs, 10-year overall survival is 68% in the
      series with longer follow up, and cancer-specific survival varies from 97% to
      100%. In our series of 144 patients with median follow up of 3.2 years, 76.3% of
      the patients continue on surveillance. 24 patients (15.9%) stopped surveillance
      due to histological progression. 5 patients (21.3%) out of the 23 undergoing
      surgery presented unfavorable pathological criteria on prostatectomy specimen. No
      patient has died or developed metastases. 

PMID- 24914845
TI  - [Opportunities and risks of 5alpha reductase inhibitors in the medical management
      of Active surveillance for localized prostate cancer].
AB  - Active surveillance (AS) as a therapeutic option is already integrated as a
      primary treatment strategy in low risk localized prostate cancer (PCa). There is
      a recent interest for the search of therapeutic interventions that result in a
      delay in the progression of such indolent cancers. The evaluation of the possible
      implication of 5 ARI drugs in the reduction of the risk of progression of PCa was
      enacted by the results of the clinical trials PCPT (Prostate Cancer Prevention
      Trial) and REDUCE (Reduction by Dutasteride of Prostate Cancer Events study). The
      results of the REDEEM clinical trial (Reduction by Dutasteride of clinical
      progression events in expectant management trial) revealed a delay in PCa
      progression favoring Dutasteride in comparison with placebo, being advanced age
      and PSA Density independent predictive factors for pathologic progression.
      Evidences regarding the influence of 5 ARIs in the evolution of AS patients come
      from few studies with limited follow up. Thus, the conclusions probably are far
      from being consiidered as definitive. 

PMID- 24914846
TI  - [New biomarkers to optimize the selection and follow up of patients with prostate
      cancer on active surveillance].
AB  - Identification of biomarkers that, at the time of diagnosis of prostate cancer
      (PCa), are associated with presence of disease or a more aggressive behavior will
      transform the clinical management of this disease. If both patients and
      clinicians would have reproducible and valid tools to estimate the specific risk
      of morbidity associated with PCa, then many patients would opt to and join active
      surveillance (AS) protocols, and consequently costs and comorbidities associated
      with the current overtreatment of prostate cancer would be reduced. Thus, a
      biomarker, or a panel of biomarkers, with high specificity to identify patients
      at risk for progression in AS protocols, would identify those men who could
      benefit from less intensive AS protocols with less repeated biopsies, so reducing
      the risk and cost of these invasive procedures. In this review we try to offer an
      overview of the new markers identified by genomic techniques and to discuss their
      potential role in an AS context. Moreover, the AS protocol offers an adequate
      setting for validation of biomarkers associated to disease progression.

PMID- 24914847
TI  - An update on imaging techniques to optimize active surveillance in prostate
      cancer.
AB  - Thanks to the higher diagnostic accuracy and safety, new imaging techniques
      provide future prospects in terms of patient management and follow-up in active
      surveillance (AS) protocols. Two of the aims of developing new imaging techniques
      are improving patient selection criteria and to improve follow-up with non
      invasive tests. Another objective is to improve the diagnostic performance of
      biopsies; this would enable physicians to switch from blind systematic TRUS
      guided biopsies to targeted biopsies to reduce the amount of biopsies required
      and reduce the diagnostic rate of clinically insignificant cancers. The notable
      advances of multi-parametric or functional prostatic imaging (mpMRI) have led to
      perceptible diagnostic improvements as it they does do not only provide
      information regarding size and location but also tumor aggressiveness. MRI has
      proven to be the most reliable non-invasive technique to be able to exclude
      patients with clinically significant cancer and thus gain acceptance in AS
      protocols during selection, confirmation and follow-up of AS patients. This
      chapter reviews the notable impact of multiparametric prostate MRI (mpMRI) on
      improving both diagnostic accuracy and follow-up. The second point describes the
      technical advances in the field of transrectal ultrasound imaging, aiming at
      improving the diagnostic accuracy of biopsies given their increased accessibility
      and real-time use. 

PMID- 24914848
TI  - [Active surveillance in prostate cancer and quality of life].
AB  - Active surveillance was born as a therapeutic strategy for a well selected group
      of patients with low risk prostate cancer with the aim to defer or completely
      avoid the negative impact of secondary effects of curative therapies.
      Nevertheless, the patient who chooses this treatment does it at the expense of
      greater anxiety and doubts about the possible progression of the disease. The
      main psychological features influencing the quality of life of these patients
      are, on one hand anxiety, due to the uncertainty and fear to disease progression,
      and on the other hand, the difficult decision making process. Among the factors
      that seem to influence the election are: urologist's recommendation, effects on
      urinary function, age and impact of the therapy on sexual function. In the
      timorous journey walked, it is recommended to apply psycho-educational programs,
      with the objective of increasing the perceived control and adaptive
      confrontation. We propose an intervention with 4 group sessions, the objectives
      of which would be first to improve the decision making process and diminish the
      fear to progression and, second to reinforce the information already given at the
      time of diagnosis and increase the sensation of control, e.g promoting healthy
      habits. 

PMID- 24914849
TI  - [Criticisms to patient selection in active surveillance in prostate cancer].
AB  - OBJECTIVES: Active treatment in localized prostate cancer, in its various types,
      is assumed as a valid alternative. The effect of the possible overtreatment has
      raised that options such as active surveillance are offered as an alternative to
      active treatments, without evidence about its validity in many points. The
      objective of this study is to analyze the current controversies to define
      candidates to this alternative, follow up criteria, impact on quality of life and
      evidence bases to do it. METHODS: We perform an analysis updating the Medline
      search with the terms localized prostate cancer and active surveillance,
      analyzing the articles and their evidence, as well as guidelines recommendations.
      RESULTS: Selection criteria for candidates to active surveillance are
      heterogeneous, without evidence of uniformity. Likewise, follow up and its
      criteria or progression are not well defined. The impact on progression, or delay
      in decision-making, have not been analyzed and we lack of studies of highest
      evidence including comparative studies for cancer specific or global survival
      results. CONCLUSIONS: Although AS seems to be a reasonable alternative in many
      patients with localized prostate cancer, we still need to define many features of
      inclusion and decision-making. Comparative studies are needed to better define
      selection and validity of active surveillance.

PMID- 24914850
TI  - [Economic features of active surveillance].
AB  - In a context where there is evidence that not every patient with low risk
      prostate cancer needs to be treated from the start, active treatments are
      expensive and public health care systems need to save money, studies on cost
      effectiveness are a priority. To elaborate this article, we reviewed the
      publications on cost and cost-effectiveness of localized prostate cancer
      treatments that include active surveillance. In patients with low risk localized
      prostate cancer active surveillance is more cost-effective than active treatment.
      With time active surveillance may be more expensive than brachytherapy or radical
      prostatectomy. The frequency of prostatic biopsies and the percentage of
      conversions to active treatment will be determinant in final costs of active
      surveillance. 

PMID- 24914851
TI  - A novel dual-emission ratiometric fluorescent nanoprobe for sensing and
      intracellular imaging of Zn2+.
AB  - The integration of unique characteristics of nanomaterials with highly specific
      recognition elements, such as biomolecules and organic molecules, are the
      foundation of many novel nanoprobes for bio/chemical sensing and imaging. In the
      present report, branched polyethylenimine (PEI) was grafted with 8-chloroacetyl
      aminoquinoline to synthesize a water-soluble and biocompatible quinoline-based
      Zn(2+) probe PEIQ. Then the PEIQ was covalently conjugated to [Ru(bpy)3](2+)
      encapsulated SiNPs to obtain the ratiometric fluorescence nanoprobe which
      exhibits a strong fluorescence emission at 600 nm and a negligible fluorescence
      emission at 500 nm in the absence of Zn(2+) upon a single wavelength excitation.
      After the addition of different amounts of Zn(2+), the fluorescence intensity at
      500 nm increased continuously while the fluorescence intensity at 600 nm remained
      stable, thus changing the dual emission intensity ratios and displaying
      continuous color changes from red to green which can be clearly observed by the
      naked eye. The nanoprobe exhibits good water dispersivity, biocompatibility and
      cell permeability, high selectivity over competing metal ions, and high
      sensitivity with a detection limit as low as 0.5 MUM. Real-time imaging of Zn(2+)
      in A549 cells has also been realized using this novel nanoprobe.

PMID- 24914852
TI  - Thymine-based molecular beacon for sensing adenosine based on the inhibition of S
      adenosylhomocysteine hydrolase activity.
AB  - This study presents a thymine (T)-based molecular beacon (MB) used for probing S
      adenosylhomocysteine hydrolase (SAHH)-catalyzed hydrolysis of S
      adenosylhomocysteine (SAH) and for sensing adenosine based on the inhibition of
      SAHH activity. The designed MB (T8-MB-T8) contained a 15-mer loop and a stem that
      consisted of a pair of 8-mer T bases, a fluorophore unit at the 5'-end, and a
      quencher unit at the 3'-end. In the presence of Hg(2+), a change in the
      conformation of T8-MB-T8 placed the fluorophore unit and the quencher in
      proximity to each other and caused collisional quenching of fluorescence between
      them. The Hg(2+)-induced fluorescence quenching of T8-MB-T8 occurred because the
      Hg(2+) induced T-T mismatches to form stable T-Hg(2+)-T coordination in the MB
      stem. SAHH catalyzed the hydrolysis of SAH to produce homocysteine. The generated
      homocysteine enabled the Hg(2+) to be removed from a hairpin-shaped T8-MB-T8
      through the formation of a strong Hg(2+)-S bond, leading to the restoration of
      its fluorescence. The T8-MB-T8 . Hg(2+) probe showed a limit of detection for
      SAHH of 4 units L(-1) (approximately 0.24 nM) and was reusable for detecting the
      SAHH/SAH system. Because adenosine was an effective SAHH activity inhibitor, the
      T8-MB-T8 . Hg(2+) probe combining the SAHH and SAH systems was used for sensitive
      and selective detection of adenosine in urine without the interference of other
      adenosine analogs.

PMID- 24914853
TI  - Room-temperature pressure-induced nanostructural CuInTe(2) thermoelectric
      material with low thermal conductivity.
AB  - A room-temperature high-pressure synthesis method is proposed as an alternative
      way to induce nanoscale structural disorder in the bulk thermoelectric CuInTe2
      matrix. This disorder stems from the coexistence of distinct domains with
      different degrees and geometries of disorder at Cu/In cation sites. The lattice
      thermal conductivity of high-pressure-treated CuInTe2 is substantially less than
      that of hot-pressed CuInTe2. The Debye-Callaway model reveals that the reduced
      lattice thermal conductivity is mainly attributed to disorder at the Cu/In cation
      sites and stacking faults, which were probably created during formation of the
      high-pressure-treated phases. This study demonstrates that room-temperature high
      pressure synthesis can produce a radical change in the crystal structure and
      physical properties of conventional thermoelectric materials. 

PMID- 24914854
TI  - Structural insights into the coenzyme mediated monomer-dimer transition of the
      pro-apoptotic apoptosis inducing factor.
AB  - The apoptosis-inducing factor (AIF) is a mitochondrial-flavoprotein that, after
      cell death induction, is distributed to the nucleus to mediate chromatinolysis.
      In mitochondria, AIF is present in a monomer-dimer equilibrium that after
      reduction by NADH gets displaced toward the dimer. The crystal structure of the
      human AIF (hAIF):NAD(H)-bound dimer revealed one FAD and, unexpectedly, two
      NAD(H) molecules per protomer. A 1:2 hAIF:NAD(H) binding stoichiometry was
      additionally confirmed in solution by using surface plasmon resonance. The here
      newly discovered NAD(H)-binding site includes residues mutated in human
      disorders, and accommodation of the coenzyme in it requires restructuring of a
      hAIF portion within the 509-560 apoptogenic segment. Disruption of interactions
      at the dimerization surface by production of the hAIF E413A/R422A/R430A mutant
      resulted in a nondimerizable variant considerably less efficiently stabilizing
      charge-transfer complexes upon coenzyme reduction than WT hAIF. These data reveal
      that the coenzyme-mediated monomer-dimer transition of hAIF modulates the
      conformation of its C-terminal proapoptotic domain, as well as its mechanism as
      reductase. These observations suggest that both the mitochondrial and apoptotic
      functions of hAIF are interconnected and coenzyme controlled: a key information
      in the understanding of the physiological role of AIF in the cellular life and
      death cycle. 

PMID- 24914855
TI  - Design, synthesis, and biological evaluation of various alpha-substituted
      benzylpyrroles based on the structures of insecticidal chlorfenapyr and natural
      pyrrolomycins.
AB  - On the basis of the structures of chlorfenapyr and dioxapyrrolomycin, a series of
      2-benzylpyrroles with a hydroxyl, an alkyloxy, an acyloxy, an alkylsulfanyl, or
      an oxime moiety at the alpha-position of benzyl were designed and synthesized.
      Their insecticidal, acaricidal, and fungicidal activities were extensively
      investigated. The structure-activity relationship showed that benzylpyrroles
      bearing shorter alpha-alkyloxy groups gave better activities against most of the
      insect species; the alkylation of pyrrole usually gave increased activity. Among
      all compounds, (4-bromo-2-(alpha-(2,2,2-trifluoroethoxy)-4-chlorobenzyl)-1
      (ethoxymethyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile) (5'j) exhibited the
      most outstanding insecticidal activities against oriental armyworm (IC50=10 mg L
      1), diamondback moth (0.07 mg L-1), corn borer (50 mg L-1), and mosquito (0.04 mg
      L-1), which are very close to those of chlorfenapyr (5, 0.08, <25, and <0.025 mg
      L-1, respectively). In addition, some compounds also exhibited a broad or
      selective fungicidal spectrum.

PMID- 24914856
TI  - Screening of DNA aptamers against myoglobin using a positive and negative
      selection units integrated microfluidic chip and its biosensing application.
AB  - An aptamer screening method using a positive and negative selection units
      integrated microfluidic chip was introduced. Here, myoglobin (Myo), one of the
      early markers to increase after acute myocardial infarction, was used as the
      model. After 7-round selection, the aptamers, which exhibited dissociation
      constants (K(d)) in the nanomolar range (from 4.93 to 6.38 nM), were successfully
      obtained using a positive and negative selection units integrated microfluidic
      chip. The aptamer with the highest affinity (K(d) = 4.93 nM) was then used for
      the fabrication of a label-free supersandwich electrochemical biosensor for Myo
      detection based on target-induced aptamer displacement. The detection limit of
      this aptamer-based electrochemical biosensor was 10 pM, which was significantly
      lower than that of those previous antibody-based biosensors for Myo detection.
      This work may not only develop a strategy for screening aptamer but also offer
      promising alternatives to the traditional analytical and immunological methods
      for Myo detection.

PMID- 24914858
TI  - [Long-term sequelae of the economic crisis and inequalities in health].

PMID- 24914857
TI  - [Declaration of transparency: promoting a more complete, honest and adequate
      publication of scientific articles].

PMID- 24914859
TI  - [Epidemic cholera in complex emergencies].
AB  - BACKGROUND: Complex emergencies are situations of violence, nutritional
      insecurity and population displacement of increasing frequency and intensity
      which pose a serious public health problem to the affected populations.
      Communicable diseases, especially waterborne diseases as cholera, cause up to 75%
      of morbidity and mortality in complex emergencies. The objective is to analyze
      the cholera epidemics in complex emergencies and cholera risk factors associated
      with the emergency. METHODS: This descriptive study analyzes cholera epidemics in
      complex emergencies in affected countries between 2000 and 2011 by reviewing the
      information formally published and unpublished reports from field organizations
      and aid agencies. Indicators of incidence, mortality and case-fatality were used.
      RESULTS: The mean annual incidence of cholera in areas of complex emergency was
      1.2 per 1,000 population (95% CI = 0.5 to 1.9) and the average fatality of
      epidemics was 4.08% (95% CI = 3.3 to 4.86). CONCLUSIONS: In the cases studied the
      following specific risk factors of complex emergencies are present and amplify
      the impacts of cholera: serious deficiencies in water and sanitation, over
      crowding, weak health system, lack of previous immunity of the affected
      population and introduction or reintroduction of causative agent.

PMID- 24914860
TI  - [Ocular and visual alterations in computer workers contact lens wearers: scoping
      review].
AB  - BACKGROUND: The high number of computer workers wearing contact lenses raises the
      question whether the sum of these two risk factors for eye health may cause a
      worsening of Computer Vision Syndrome. The aim of this review is to synthesize
      the knowledge about ocular and visual alterations related with computer use in
      contact lens wearers. METHODS: International review of scientific papers (2003
      2013) in Spanish and English, using Scoping Review method, in Medline through
      PubMed and in Scopus. RESULTS: The initial search provided 114 references, after
      applying inclusion/exclusion criteria six of them were included. All of them
      reveal that symptoms when using computer are more prevalent in contact lens
      wearers, with values of symptoms presentation prevalence ranging from 95.0% to
      16.9% in wearers and from 57.5% to 9.9% in non-wearers, and four times more
      likely to develop dry eye [OR: 4.07 (95% CI: 3.52 to 4.71)]. CONCLUSION: Computer
      workers suffer more ocular and visual disturbances if they also are contact lens
      users, but studies are few and non conclusive. Likewise, further research
      regarding contact lens type and their conditions of use, both in symptoms and
      tear quality and ocular surface are needed. Silicone hydrogel lenses are
      associated with more comfort.

PMID- 24914861
TI  - [Barriers for introducing a health technology assessment organization to inform
      health care decision-making in the Spanish National Health System].
AB  - BACKGROUND: To identify difficulties, obstacles and limitations to establish an
      organizational structure devoted to the evaluation of healthcare technologies for
      incorporation, maintenance or removal from the services portfolio of the Spanish
      National Health System (sNHS). METHODS: Panel of 14 experts, structured according
      to processes adapted from brainstorming, nominal group, and Rand consensus method
      techniques. RESULTS: The panel proposed 77 items as potential obstacles to the
      establishment of an official and independent "agency" able to inform on sNHS
      healthcare benefits funding or selective disinvestment. These items were focused
      on: 1) lack of political motivation to introduce the cost-effectiveness analysis
      from the state and regional governments and lack of independence and transparency
      of the evaluation processes, 2) the tension between a decentralized health system
      and evaluation activities with significant scale economies, 3) technical
      difficulties of the evaluation processes, including their ability to influence
      decision making and 4) social and professional refusal to the exclusion of
      healthcare benefits when it is perceived as indiscriminate. CONCLUSION: Although
      there is a different number and type of obstacles for developing the capacity of
      the sNHS to include or exclude healthcare benefits based on the evaluation of
      their effectiveness and efficiency, experts place in the political arena
      (political motivation, transparency, governance) the main difficulties to advance
      in this field.

PMID- 24914862
TI  - [Impact of the Royal Decree-Law 16/2012 on the number of prescriptions and
      pharmaceutical expenditures].
AB  - BACKGROUND: this research aims to understand if the consequences on drug
      expenditures and number of prescriptions of Royal Decree-Law 16/2012 as estimated
      by the Ministry of Health, Social Services and Equality (MHSSE) are similar to
      those found by using common statistical approaches. In addition, several models
      have been built to forecast the evolution of both variables for the period
      September 2013-December 2014. METHODS: the Box-Jenkins methodology and the Box
      Tiao intervention analysis were applied to data of the period 2003-13 to forecast
      the monthly values of the number of prescriptions and pharmaceutical
      expenditures. Forecasts were used in a counter-factual analysis to be compared to
      the actual values of prescriptions and drug expenditures. Moreover, forecasts for
      the period September 2013 to December 2014 were obtained to observe the impact of
      the policy in the future. RESULTS: the counterfactual analysis estimated a
      decrease in the number of prescriptions of 12.18% and 12.83% in the
      pharmaceutical expenditure; these figures were 12,75% and 14,03% respectively,
      when the intervention analysis was used. CONCLUSION: the estimated reduction in
      the number of prescriptions for the period June 2012-August 2013 was similar to
      the figure offered by the MHSSE, while the reduction in the drug expenditure
      series was smaller. The Box-Jenkins methodology generated low forecast errors
      (less than 3%) what makes this procedure useful to reliably anticipate future
      consumptions.

PMID- 24914863
TI  - [Development of a predictive risk model for unplanned admissions in the Basque
      Country].
AB  - BACKGROUND: Hospitalizations are undesirable events that can be avoided to some
      degree through proactive interventions. The objective of this study is to
      determine the capability of models based on Adjusted Clinical Groups (ACG), in
      our milieu, to identify patients who will present unplanned admissions in the
      following months to their classification, in both the general population and in
      subpopulations of chronically ill patients (diabetes mellitus, chronic
      obstructive pulmonary disease and heart failure). METHODS: Cross-sectional study
      which analyzes data from a two year period, of all residents over 14 years old in
      the Basque Country (N = 1,964,337). Data from the first year (demographic,
      deprivation index, diagnoses, prescriptions, procedures, admissions and other
      contacts with the health service) were used to construct the independent
      variables; hospitalizations of the second year, the dependent ones. We used the
      area under the ROC curve (AUC) to evaluate the capability of the models to
      discriminate patients with hospitalizations and calculated the positive
      predictive value and sensitivity of different cutoffs. RESULTS: In the general
      population, models for predicting admission at 6 and 12 months, as well as long
      term hospitalizations showed a good performance (AUC> 0.8), while it was
      acceptable (AUC 0.7 to 0.8) in the groups of chronic patients. CONCLUSION: A
      hospitalization risk stratification system, based on ACG, is valid and applicable
      in our milieu. These models allow classifying the patients on a scale of high to
      low risk, which makes possible the implementation of the most expensive
      preventive interventions to only a small subset of patients, while other less
      intensive ones can be provided to larger groups.

PMID- 24914864
TI  - [Municipal distribution and trend of the incidence of breast cancer in the health
      area of Leon, Spain (1996-2010)].
AB  - BACKGROUND: Breast cancer is the most common amongst women. The aim of this study
      was to analyze the incidence and geographical distribution of breast cancer in
      the health area of Leon. METHODS: We designed an observational descriptive study
      that included women enrolled in the Hospital Tumor Registry of the Centro
      Asistencial Universitario in Leon with a diagnosis of breast malignant neoplasm
      (ICD-9: 174, ICD-10: 50) between 01/01/1996 and 31/12/2010 and resident in the
      health area of Leon. To study the spatial distribution, we estimated municipal
      relative risks (RR) smoothed by fitting the Besag, York and Mollie model and the
      posterior probability (PP) of RR > 1 using Bayesian methods. RESULTS: A total of
      2379 cases were included. The number of new cases and the crude incidence rate
      have both increased in every triennium, from 72,7 (1996-1998) to 101,5 (2008
      2010) per 100,000 women. The age adjusted rates per 100,000 women (European
      standard population) increased from 58,0 during the first triennium to 69,4
      during the last one. An average annual increase of 1,3% was observed. Several
      municipalities from the health area of Leon showed risks higher than a 10%. The
      PP were higher than 0.9 only in the municipality of Leon. CONCLUSION: The
      observed rates are among the lowest in our country. Nevertheless, the number of
      cases and the incidence rates have increased progressively.

PMID- 24914865
TI  - [Psychometric validation of the International FItness Scale (IFIS) in Colombian
      youth].
AB  - BACKGROUND: The International Fitness Scale (IFIS a 5-item version) to assess
      physical activity levels in the European population was created as part of the
      framework of the EU-funded project HELENA Study "Healthy Lifestyle in Europe by
      Nutrition in Adolescence". The objective of this study was to evaluate the test
      retest stability, internal consistency, proportion of agreement and applicability
      to Colombian young adults. METHODS: A total of 2.340 individuals (1.376 female
      and 964 male; age 18-30 years) Colombian completed the questionnaire IFIS.
      Intraclass correlation coefficients (ICC) and proportion of agreement were
      computed to assess the stability of the two test scores, with a period of 7 days
      between the two administrations. Cronbach alpha were calculated to assess the
      internal consistency of each scale and proportion of agreement was also
      calculated to measure the proportion of occasions that individuals gave the same
      score. RESULTS: The Cronbach alpha coefficient is 0.80. The reliability scores of
      the IFIS were excellent (ICC range 0.90-0.96). The proportion of agreement for
      all individual items ranged from 77-86%. Mean (+/-SD) time for questionnaire
      completion during the assessment was 3 minutes 47 seconds (+/-2 min). CONCLUSION:
      It appears to have high reliability and reproducibility. The questionnaire is now
      available to other researchers to investigate its usefulness and applicability
      across Latin American.

PMID- 24914866
TI  - [The burden of disease in Catalonia, Spain, using disability-adjusted life years
      (2005-2010)].
AB  - BACKGROUND: Burden of disease allows measuring the health of the population
      including mortality and disability. The objectives of this paper are to estimate
      the burden of disease in Catalonia, to compare the results with Spain and
      Tarragones area and to assess the contribution of the local registers to the
      estimation of the disability. METHODS: We calculated the disability-adjusted life
      years (DALYs) for 123 causes using the methodology developed by the World Health
      Organization. We compared the standardized rates with the Spanish rates. In
      Tarragones area, we calculated the DALYs, we compared them with the DALYs in
      Catalonia and moreover we used the cancer incidence local registry to calculate
      cancer burden disease. RESULTS: There were 801,140 DALYs (annual average) in
      Catalonia, 60.3% due to disability and 39.7% due to premature mortality.
      Neuropsychiatric disorders (30.9%), malignant neoplasms (15.8%) and
      cardiovascular diseases (11.3%) were the leading causes. The standardized rate of
      respiratory diseases (7.5 per 1,000) was significantly higher compared with the
      Spanish rate. Perinatal conditions (3.1 per 1,000), intentional injuries (2.2 per
      1,000) and digestive diseases (4.9 per 1,000) were significantly higher in
      Tarragones area. DALYs attributable to cancer showed an increase of 13.4 % when
      they were calculated using the incidence of cases. CONCLUSION: Noncommunicable
      diseases were the leading causes for DALYs in Catalonia. There are differences
      between territories in respiratory diseases, perinatal conditions, digestive
      diseases and intentional injures. Local registries can be very useful in order to
      calculate the DALYs.

PMID- 24914867
TI  - [Evaluation of the efficacy of the sewage treatment plant of Toledo, Spain in the
      elimination of drugs of abuse and the estimation of consumption].
AB  - BACKGROUND: in the last years, the presence of new contaminants in water has been
      rising. There are only few studies which analyze such presence. The aims were to
      determine the occurrence of drugs of abuse and their metabolites in the influent
      and effluent of the Sewage Treatment Plant (STP) in Talavera de la Reina, and the
      River Tagus, as well as to evaluate the STP removal efficiency in the elimination
      of these substances and to estimate the consumption of drugs in Talavera.
      METHODS: whe samples were taken on June 28, 2010. The presence of 5 groups of
      drugs (10 drugs of abuse and 9 metabolites) was quantified. The efficiency was
      calculated from the percentage of reduction of the concentration in the influent
      and effluent of the STP. Drug consumption was calculated from influent
      concentrations. Using a specific methodology, based on the assumption the drugs
      after they are consumed and metabolized in the human body are excreted as parent
      compounds or metabolites. Whose metabolic pathways are known, and the amount of
      drug or metabolite quantified corresponds to the dose consumed. RESULTS: ten
      substances were detected. In all sampling points appeared: Benzoiclegonina (BE)
      (cocaine metabolite), ephedrine, methadone and its metabolite EDDP. The highest
      concentrations were of BE (239 ng/L), and THC-COOH (35 ng/L), both in influent.
      In the Tagus River, the highest concentrations were of BE (5.38 ng/L) and EDDP
      (4.4 ng/L). The STP removal efficiency was up to 80% for all substances except
      for methadone (which was zero) and EDDP (increasing to leave the STP). The
      estimated consumption shows that the most consumed substances were cannabis (1.88
      grams / day) and cocaine (0.46 grams / day). CONCLUSION: the presence of drugs of
      abuse in River Tagus in Talavera demonstrates that these substances are not
      eliminated completly by STPs. Drug consumption estimate indicates that the
      population of Talavera mainly consumed cannabis and cocaine. Thus this
      methodology can complement epidemiological surveys.

PMID- 24914868
TI  - [Immigrant women care in a health intercultural mediation program].
AB  - BACKGROUND: Intercultural Mediation is a strategy for quality health care aimed
      at reducing inequalities in immigrant population. The aim is to analyse main
      reasons consultation with the mediation service, women care profile and
      characteristics of intervention. METHODS: Cross-sectional study of 339 episodes
      of care by two intercultural mediators (MI) from February 2008 to October 2011 in
      Valencia. Variables were analysed individual records of the consultations of the
      MI: reasons for referral to MI and professionals who refer, motives and problems
      identified by MI, kind of intervention, kind of derivation of MI and socio
      economic variables. To evaluate the differences between countries, X2 test was
      used for qualitative variables and one-way ANOVA test for quantitative variables.
      RESULTS: 123 women (36,3%), were referred to the MI by the Sexual and
      Reproductive Health Centre and 98 (28,9%) by the midwife. 272 women (80,24%) were
      referred for information and demand for contraception. The MI conducted health
      education and detected social problems in 67 women (19,7%) and gender violence in
      38 (11,21%). CONCLUSIONS: The women attending were Latin American immigrants
      (those of Bolivia showed more vulnerability) and were referred for contraception.
      The MI provided information, education and facilitated access to reproductive
      health services. Bolivian women showed more vulnerability factors: irregular
      situation, precarious work and low residence time.

PMID- 24914869
TI  - [New spirometric reference values for children and adolescents in Germany
      considering height and non-linear age effects: the LUNOKID-Study].

PMID- 24914870
TI  - [Prof. Dr. med. Joachim Schauer on the occasion of his 75th birthday].

PMID- 24914871
TI  - [Professor Dr. sc. med.Walter Schilling (14th July 1932-7th April 2014)].

PMID- 24914872
TI  - [Effectiveness of environmental zones in the first stage: analysis of the
      particulate matter concentration changes (PM10) in 19 German cities].

PMID- 24914873
TI  - [Reply].

PMID- 24914874
TI  - Spectrum of cyanotic congenital heart disease diagnosed by echocardiographic
      evaluation in patients attending paediatric cardiology clinic of a tertiary
      cardiac care centre.
AB  - BACKGROUND: Cyanotic CHD comprises up to 25% of cases of all causes of CHD.
      RATIONALE: There is lack of data about the present spectrum of congenital
      cyanotic heart disease in the paediatric age group. OBJECTIVE: The present study
      was undertaken to determine the spectrum of patients with congenital cyanotic
      heart disease in the paediatric age group in tertiary paediatric cardiac care
      clinic. DESIGN: Prospective observational study. SETTING: Paediatric cardiac
      clinic of a tertiary cardiac care centre. METHODS: All children aged 0-18 years
      with suspected cyanotic CHD were provisionally included in this study. They
      underwent a thorough echocardiographic evaluation, and those patients who had
      definitive diagnosis of congenital cyanotic heart disease were included for final
      analysis. RESULTS: A total of 119 children met the inclusion criteria. Tetralogy
      of Fallot and its variant were the most common congenital cyanotic heart disease
      with proportion of about 44%. Other common malformations were double outlet right
      ventricle (14%), pulmonary atresia with ventricular septal defect (8%), total
      anomalous pulmonary venous connection (7%), d-transposition of the great arteries
      (9%), tricuspid valve anomalies--tricuspid atresia and Ebstein's anomaly-
      hypoplastic left-heart syndrome, truncus arteriosus, and complex CHD such as
      single ventricle. CONCLUSION: Tetralogy of Fallot and its variants were the most
      common cyanotic heart disease diagnosed in our patients. As there were a
      significant proportion of cases with complex cyanotic CHD, paediatric
      cardiologists should be familiar with the diagnosis and management of all these
      complex congenital malformations of the heart.

PMID- 24914875
TI  - Ceria-based electrospun fibers for renewable fuel production via two-step thermal
      redox cycles for carbon dioxide splitting.
AB  - Zirconium-doped ceria (Ce(1-x)Zr(x)O2) was synthesized through a controlled
      electrospinning process as a promising approach to cost-effective, sinter
      resistant material structures for high-temperature, solar-driven thermochemical
      redox cycles. To approximate a two-step redox cycle for solar fuel production,
      fibrous Ce(1-x)Zr(x)O2 with relatively low levels of Zr-doping (0 < x < 0.1) were
      cycled in an infrared-imaging furnace with high-temperature (up to 1500  degrees
      C) partial reduction and lower-temperature (~800  degrees C) reoxidation via CO2
      splitting to produce CO. Increases in Zr content improve reducibility and
      sintering resistance, and, for x<= 0.05, do not significantly slow reoxidation
      kinetics for CO production. Cycle stability of the fibrous Ce(1-x)Zr(x)O2 (with x
      = 0.025) was assessed for a range of conditions by measuring rates of O2 release
      during reduction and CO production during reoxidation and by assessing post
      cycling fiber crystallite sizes and surface areas. Sintering increases with
      reduction temperature but occurs primarily along the fiber axes. Even after 108
      redox cycles with reduction at 1400  degrees C and oxidation with CO2 at 800 
      degrees C, the fibers maintain their structure with surface areas of ~0.3 m(2) g(
      1), higher than those observed in the literature for other ceria-based structures
      operating at similarly high temperature conditions. Total CO production and peak
      production rate stabilize above 3.0 mL g(-1) and 13.0 mL min(-1) g(-1),
      respectively. The results show the potential for electrospun oxides as sinter
      resistant material structures with adequate surface area to support rapid CO2
      splitting in solar thermochemical redox cycles.

PMID- 24914876
TI  - Magnetically actuated liquid crystals.
AB  - Ferrimagnetic inorganic nanorods have been used as building blocks to construct
      liquid crystals with optical properties that can be instantly and reversibly
      controlled by manipulating the nanorod orientation using considerably weak
      external magnetic fields (1 mT). Under an alternating magnetic field, they
      exhibit an optical switching frequency above 100 Hz, which is comparable to the
      performance of commercial liquid crystals based on electrical switching. By
      combining magnetic alignment and lithography processes, it is also possible to
      create patterns of different polarizations in a thin composite film and control
      over the transmittance of light in particular areas. Developing such magnetically
      responsive liquid crystals opens the door toward various applications, which may
      benefit from the instantaneous and contactless nature of magnetic manipulation. 

PMID- 24914877
TI  - Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic
      dysregulation: review and update.
AB  - PURPOSE OF REVIEW: The focus of this review is to compare and contrast two orphan
      disorders of late-onset hypoventilation. Specifically, rapid-onset obesity with
      hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD)
      and congenital central hypoventilation syndrome (CCHS) are distinct in
      presentation, pathophysiology, and etiology. RECENT FINDINGS: While limited new
      information is available, appreciation and understanding of rare disorders can be
      attained through case reports. Recent literature in ROHHAD has included case
      reports with new findings that may provide insight into pathophysiology involving
      possible aberrant immune process and dysregulation at the level of the
      orexinergic system. SUMMARY: The etiology of ROHHAD continues to be elusive. The
      hope is that, with growing recognition, discussion, and investigation into the
      overlap of ROHHAD with disorders outside congenital central hypoventilation
      syndrome, further advancement will be made.

PMID- 24914879
TI  - Following the right pathway: evidence-based guidelines in adolescent healthcare.

PMID- 24914878
TI  - Youth marijuana use: state of the science for the practicing clinician.
AB  - PURPOSE OF REVIEW: Despite widespread marijuana use among adolescents, accurate
      information on known health effects is poorly disseminated to clinicians and
      their patients. Amidst rapidly evolving drug policy in the United States and
      elsewhere, it is imperative that providers understand the short-term and long
      term consequences of marijuana use. RECENT FINDINGS: Research on regular
      marijuana use highlights a unique susceptibility of the developing adolescent
      brain to adverse neurocognitive and psychiatric outcomes. Although studies have
      not firmly established causality, onset of regular marijuana use in adolescence
      is associated with later decline in cognitive function, as well as with adult
      onset of psychosis and anxiety. Educational and employment outcomes may be poorer
      among regular marijuana-using adolescents. A number of other adverse respiratory,
      cardiovascular, endocrine and gastrointestinal associations with regular
      marijuana use have also been established. Good screening tools and promising
      brief intervention and behavioral treatment programs are available to clinicians,
      who are in a position to identify problematic marijuana use among adolescents.
      SUMMARY: A common misperception among youth is that marijuana use is without
      harm. However, adolescent marijuana use may have measurable, durable, and
      potentially irreversible effects on later cognitive function and mental health.

PMID- 24914880
TI  - Compound 21, a selective angiotensin II type 2 receptor agonist, downregulates
      lipopolysaccharide-stimulated tissue factor expression in human peripheral blood
      mononuclear cells.
AB  - Intricate interrelationships connect tissue factor (TF), the principal initiator
      of the clotting cascade, to inflammation, a cross-talk amplified by locally
      active angiotensin II, a proinflammatory agent with direct TF-stimulating
      properties mediated by the angiotensin II type 1 receptor (AT1R)s. However,
      angiotensin II also stimulates angiotensin II type 2 receptor (AT2R)s and they
      may as well contribute to TF expression, a possibility in need of further
      evaluation. We investigated the effect of C21, a highly specific AT2R agonist, on
      TF antigen (ELISA), procoagulant activity (PCA, one-stage clotting assay) and TF
      mRNA (real-time PCR) in peripheral blood mononuclear cell (PBMC)s activated by
      lipopolysaccharide (LPS), a pro-inflammatory and procoagulant stimulus. C21
      downregulated LPS-stimulated TF antigen, PCA and TF mRNA, an effect abolished by
      PD123 319, a selective AT2R antagonist, and left unchanged by omesartan, a
      selective AT1R antagonist. PD123 319 per se did not affect LPS-induced TF
      expression while omesartan inhibited and BAY 11-7082, a specific NFkappaB
      inhibitor, abolished endotoxin-activated procoagulant activity (PCA). C21, a
      selective AT2R agonist, downregulates the transcriptional expression of TF in LPS
      activated PBMCs, a finding consistent with the existence in PBMCs of AT2Rs whose
      stimulation attenuates inflammation-mediated procoagulant responses. The data
      open insofar unexplored and potentially relevant facets to our understanding of
      the complex links connecting angiotensin II to inflammation and coagulation. 

PMID- 24914881
TI  - Synthesis of hexagonal boron nitride graphene-like few layers.
AB  - Self-standing highly crystallized hexagonal boron nitride (h-BN) mono-, bi- and
      few-layers have been obtained for the first time via the Polymer Derived Ceramics
      (PDCs) route by adding lithium nitride (Li3N) micropowders to liquid-state
      polyborazylene (PBN). Incorporation of Li3N as a crystallization promoter allows
      the onset of crystallization of h-BN at a lower temperature (1200  degrees C)
      than under classical conditions (1800  degrees C). The hexagonal structure was
      confirmed by both electron and X-ray diffraction.

PMID- 24914882
TI  - Precis on The Cognitive-Emotional Brain.
AB  - In The Cognitive-Emotional Brain (Pessoa 2013), I describe the many ways that
      emotion and cognition interact and are integrated in the brain. The book
      summarizes five areas of research that support this integrative view and makes
      four arguments to organize each area. (1) Based on rodent and human data, I
      propose that the amygdala's functions go beyond emotion as traditionally
      conceived. Furthermore, the processing of emotion-laden information is capacity
      limited, thus not independent of attention and awareness. (2) Cognitive-emotional
      interactions in the human prefrontal cortex (PFC) assume diverse forms and are
      not limited to mutual suppression. Particularly, the lateral PFC is a focal point
      for cognitive-emotional interactions. (3) Interactions between motivation and
      cognition can be seen across a range of perceptual and cognitive tasks.
      Motivation shapes behavior in specific ways--for example, by reducing response
      conflict or via selective effects on working memory. Traditional accounts, by
      contrast, typically describe motivation as a global activation independent of
      particular control demands. (4) Perception and cognition are directly influenced
      by information with affective or motivational content in powerful ways. A dual
      competition model outlines a framework for such interactions at the perceptual
      and executive levels. A specific neural architecture is proposed that embeds
      emotional and motivational signals into perception and cognition through multiple
      channels. (5) A network perspective should supplant the strategy of understanding
      the brain in terms of individual regions. More broadly, in a network view of
      brain architecture, "emotion" and "cognition" may be used as labels of certain
      behaviors, but will not map cleanly into compartmentalized pieces of the brain.

PMID- 24914884
TI  - Lesions of the Bartholin gland: a review.
AB  - Most lesions of the Bartholin gland are cysts or abscesses. Clinicians are taught
      that lesions of the Bartholin gland occurring in older women should raise the
      differential diagnosis of malignancy, although these are uncommon. A variety of
      more unusual and rare lesions of the Bartholin gland have been reported. This
      review focuses on these less common entities, which must be considered as well
      when encountering pathology of the Bartholin gland. 

PMID- 24914883
TI  - Associations between religion-related factors and cervical cancer screening among
      Muslims in greater chicago.
AB  - OBJECTIVE: This study aimed to assess rates of Papanicolaou (Pap) testing and
      associations between religion-related factors and these rates among a racially
      and ethnically diverse sample of American Muslim women. MATERIALS AND METHODS: A
      community-based participatory research design was used in partnering with the
      Council of Islamic Organizations of Greater Chicago to recruit Muslim women
      attending mosque and community events. These participants self-administered
      surveys incorporating measures of fatalism, religiosity, perceived
      discrimination, Islamic modesty, and a marker of Pap test use. RESULTS: A total
      of 254 survey respondents were collected with nearly equal numbers of Arabs,
      South Asians, and African American respondents. Of these respondents, 84% had
      obtained a Pap test in their lifetime, with individuals who interpret disease as
      a manifestation of God's punishment having a lower odds of having had Pap testing
      after controlling for sociodemographic factors (odds ratio [OR]=0.87, 95% CI=0.77
      1.0). In multivariate models, living in the United States for more than 20 years
      (OR=4.7, 95% CI=1.4-16) and having a primary care physician (OR=7.7, 95% CI=2.5
      23.4) were positive predictors of having had a Pap test. Ethnicity, fatalistic
      beliefs, perceived discrimination, and modesty levels were not significantly
      associated with Pap testing rates. CONCLUSIONS: To our knowledge, this is the
      first study to assess Pap testing behaviors among a diverse sample of American
      Muslim women and to observe that negative religious coping (e.g., viewing health
      problems as a punishment from God) is associated with a lower odds of obtaining a
      Pap test. The relationship between religious coping and cancer screening
      behaviors deserves further study so that religious values can be appropriately
      addressed through cancer screening programs.

PMID- 24914885
TI  - Variation in apoptotic gene expression in cervical cancer through oligonucleotide
      microarray profiling.
AB  - OBJECTIVE: The current study aimed to investigate the molecular basis of cervical
      cancer development using a microarray to identify the differentially expressed
      genes. This study also aimed to detect apoptosis genes and proteins to find those
      genes most aberrantly expressed in cervical cancer and to explore the cause of
      Uighur cervical cancer. METHODS: An analysis of gene expression profiles obtained
      from cervical cancer cases was performed. Total RNA was prepared from 10 samples
      of cervical carcinoma and normal cervix and was hybridized to Affymetrix
      oligonucleotide microarrays with probe sets complementary to more than 20,000
      transcripts. Several genes of the apoptosis pathway, which were differentially
      regulated, included BCL2, BCLXL, and c-IAP1. These were validated by quantitative
      reverse transcription-polymerase chain reaction and immunohistochemical staining
      on an independent set of cancer and control specimens. RESULTS: Unsupervised
      hierarchical clustering of the expression data readily distinguished the normal
      cervix from cancer. Supervised analysis of gene expression data identified 1,326
      and 1,432 genes that were upregulated and downregulated, respectively; a set of
      genes belonging to the apoptosis pathways were upregulated or downregulated in
      patients with cervical cancer. BCL2, BCLXL, and c-IAP1 were found to be
      upregulated in late-stage cancer compared to early-stage cancer. CONCLUSIONS:
      These findings provide a new understanding of the gene expression profile in
      cervical cancer. BCL2, BCLXL, and c-IAP1 might be involved in cancer progression.
      The pathway analysis of expression data showed that the BCL2, BCLXL, and c-IAP1
      genes were coordinately differentially regulated between cancer and normal cases.
      Our results may serve as basis for further development of biomarkers for the
      diagnosis and treatment of cervical cancer.

PMID- 24914886
TI  - Lesions of the clitoris: a review.
AB  - The clitoris may become involved by vulvar lesions. There are also lesions
      arising from the clitoris. A familiarity with these lesions is necessary for the
      high index of suspicion needed for their diagnosis. 

PMID- 24914888
TI  - "Soldier-Sergeant-Soldier" triblock copolymers: revealing the folded structure of
      single-chain polymeric nanoparticles.
AB  - "Soldiers-Sergeant-Soldiers" experiments performed on single-chain polymeric
      nanoparticles (SCPNs) with an ABA-type triblock architecture carrying chiral and
      achiral benzene-1,3,5-tricarboxamides (BTAs) in different blocks reveal that the
      BTAs form segregated, multiple stacks in a single SCPN. 

PMID- 24914887
TI  - Evaluation of a cervicography-based program to ensure quality of visual
      inspection of the cervix in HIV-infected women in Johannesburg, South Africa.
AB  - OBJECTIVE: To determine whether a quality assurance (QA) program using digital
      cervicography improved the performance of a visual inspection with acetic acid
      (VIA) to detect cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) in
      HIV-infected women in Johannesburg, South Africa. MATERIALS AND METHODS: Visual
      inspection with acetic acid was performed among HIV-infected women, aged 18 to 65
      years, in Johannesburg, South Africa. Nurses received 2 weeks of training on the
      VIA procedure. The VIA interpretation was performed in real time. The VIA results
      were then photographed using a retail available digital camera. A gynecologist
      and medical officer reviewed the VIA digital images within 2 weeks of the
      procedure. Colposcopic biopsy was performed on all women with positive VIA and
      25% negative VIA results. Sensitivity and specificity of VIA for the detection of
      CIN 2+ were compared between the nurses and physicians at the beginning and at
      the end of the study. RESULTS: Positive VIA results were found in 541 (45%) of
      the 1,202 participating women. The sensitivity of VIA to predict CIN 2+ was
      improved from 65% to 75% (p = .001) with the addition of digital cervicography
      and specialist review. There was no statistical difference in the sensitivity of
      the VIA readings when comparing the first 600 participants to the final 593
      participants between the nurses (p = .613) and physicians (p = .624).
      CONCLUSIONS: Quality assurance performed by specialists using digital
      cervicography improved the sensitivity of VIA. There was no difference in
      sensitivity in interpreting VIA between the beginning and the end of the study.
      Quality assurance should form a cornerstone of any VIA program to improve
      sensitivity in detecting CIN 2+ lesions.

PMID- 24914889
TI  - The new DSM-5 diagnosis of mild neurocognitive disorder and its relation to
      research in mild cognitive impairment.
AB  - The Diagnostic Statistical Manual-5 (DSM-5) has included a category named the
      neurocognitive disorder which was formally known in DSM-IV as 'dementia,
      delirium, amnestic, and other cognitive disorders'. The DSM-5 distinguishes
      between 'mild' and 'major' neurocognitive disorders. Major neurocognitive
      disorder replaces the DSM-IV's term 'dementia or other debilitating conditions'.
      A pivotal addition is 'mild neurocognitive disorder (mNCD)' defined by a
      noticeable decrement in cognitive functioning that goes beyond normal changes
      seen in aging. It is a disorder that may progress to dementia - importantly, it
      may not. Presently, our understanding of mNCD is derived from research on mild
      cognitive impairment (MCI). Whereas there is currently no clear treatment for
      mNCD, many experimental therapies now and into the future will focus upon
      secondary prevention, namely decreasing the risk of progression to major NCD. In
      this article, we will focus on mNCD by reviewing the relevant literature on MCI.
      We will review the research on the incidence and prevalence of MCI, conversion
      rates from MCI to dementia, risk factors for conversion of MCI to dementia,
      comorbidity of MCI with other neuropsychiatric disorders (NPS), and the
      development of treatment strategies for neuropsychiatric disorders in MCI. The
      presence of NPS is common among individuals with MCI and is an important risk for
      progression to dementia. However, there has been little research on effective
      treatments for NPS in MCI. Clinicians and investigators must determine if the
      treatment of the NPS in mNCD will improve quality of life and help reduce the
      progression of the cognitive impairment. 

PMID- 24914890
TI  - Macrophage elastase suppresses white adipose tissue expansion with cigarette
      smoking.
AB  - Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced
      emphysema, yet its role in other smoking related pathologies remains unclear. The
      weight suppressing effects of smoking are a major hindrance to cessation efforts,
      and MMP12 is known to suppress the vascularization on which adipose tissue growth
      depends by catalyzing the formation of antiangiogenic peptides endostatin and
      angiostatin. The goal of this study was to determine the role of MMP12 in adipose
      tissue growth and smoking-related suppression of weight gain. Whole body weights
      and white adipose depots from wild-type and Mmp12-deficient mice were collected
      during early postnatal development and after chronic CS exposure. Adipose tissue
      specimens were analyzed for angiogenic and adipocytic markers and for content of
      the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1
      adipocytes were treated with adipose tissue homogenate to examine its effects on
      vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content
      and activity were increased in the adipose tissue of wild-type mice at 2 weeks of
      age, leading to elevated endostatin production, inhibition of VEGF secretion, and
      decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels
      subsided, and the protein was no longer detectable. However, chronic CS exposure
      led to macrophage accumulation and restored adipose MMP12 activity, thereby
      suppressing adipose tissue mass and vascularity. Our results reveal a novel
      systemic role for MMP12 in postnatal adipose tissue expansion and smoking
      associated weight loss by suppressing vascularity within the white adipose tissue
      depots. 

PMID- 24914892
TI  - Easy access to Evans' oxazolidinones. Stereoselective synthesis and antibacterial
      activity of a new 2-oxazolidinone derivative.
AB  - An interesting new approach was developed for the synthesis of Evans' chiral
      auxiliaries with excellent yields. In turn, another new stereoselective and
      efficient strategy has also allowed for the preparation of a 2-oxazolidinone
      derivative in 34% overall yield from the Morita-Baylis-Hillman adduct. The
      antibacterial activity of this oxazolidinone was tested against Staphylococcus
      aureus strains isolated from animals with mastitis infections. 

PMID- 24914893
TI  - Complement fixing polysaccharides from Terminalia macroptera root bark, stem bark
      and leaves.
AB  - The root bark, stem bark and leaves of Terminalia macroptera were sequentially
      extracted with ethanol, 50% ethanol-water, and 50  degrees C and 100  degrees C
      water using an accelerated solvent extractor. Ten bioactive purified
      polysaccharide fractions were obtained from those crude extracts after anion
      exchange chromatography and gel filtration. The polysaccharides and their native
      extracts were characterized with respect to molecular weight, chemical
      compositions and effects in the complement assay. The chemical compositions
      showed that the polysaccharides are of pectic nature. The results indicated that
      there was no great difference of the complement fixation activities in the crude
      extracts from the different plant parts when extracting with the accelerated
      solvent extraction system. The purified polysaccharide fractions 100WTSBH-I-I and
      100WTRBH-I-I isolated from the 100  degrees C water extracts of stem and root
      bark respectively, showed the highest complement fixation activities. These two
      fractions have rhamnogalacturonan type I backbone, but only 100WTSBH-I-I contains
      side chains of both arabinogalactan type I and II. Based on the yield and
      activities of the fractions studied those from the root bark gave highest
      results, followed by those from leaves and stem bark. But in total, all plant
      materials are good sources for fractions containing bioactive polysaccharides. 

PMID- 24914894
TI  - Organic liquids-responsive beta-cyclodextrin-functionalized graphene-based
      fluorescence probe: label-free selective detection of tetrahydrofuran.
AB  - In this study, a label-free graphene-based fluorescence probe used for detection
      of volatile organic liquids was fabricated by a simple, efficient and low-cost
      method. To fabricate the probe, a bio-based beta-cyclodextrin (beta-CD) was
      firstly grafted on reduced graphene surfaces effectively and uniformly, as
      evidenced by various characterization techniques such as Ultraviolet/Visible
      spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction,
      thermogravimetric analysis, scanning electron microscopy and transmission
      electron microscopy. The subsequent inclusion of Rhodamine B (RhB) into the inner
      cavities of the beta-CD grafted on the graphene surfaces was achieved easily by a
      solution mixing method, which yielded the graphene-based fluorescent switch-on
      probe. In addition, the gradual and controllable quenching of RhB by Fluorescence
      Resonance Energy Transfer from RhB to graphene during the process of stepwise
      accommodation of the RhB molecules into the beta-CD-functionalized graphene was
      investigated in depth. A wide range of organic solvents was examined using the as
      fabricated fluorescence probe, which revealed the highest sensitivity to
      tetrahydrofuran with the detection limit of about 1.7 MUg/mL. Some insight into
      the mechanism of the different responsive behaviors of the fluorescence sensor to
      the examined targets was also described. 

PMID- 24914891
TI  - The hnRNP-Q protein LIF2 participates in the plant immune response.
AB  - Eukaryotes have evolved complex defense pathways to combat invading pathogens.
      Here, we investigated the role of the Arabidopsis thaliana heterogeneous nuclear
      ribonucleoprotein (hnRNP-Q) LIF2 in the plant innate immune response. We show
      that LIF2 loss-of-function in A. thaliana leads to changes in the basal
      expression of the salicylic acid (SA)- and jasmonic acid (JA)- dependent defense
      marker genes PR1 and PDF1.2, respectively. Whereas the expression of genes
      involved in SA and JA biosynthesis and signaling was also affected in the lif2-1
      mutant, no change in SA and JA hormonal contents was detected. In addition, the
      composition of glucosinolates, a class of defense-related secondary metabolites,
      was altered in the lif2-1 mutant in the absence of pathogen challenge. The lif2-1
      mutant exhibited reduced susceptibility to the hemi-biotrophic pathogen
      Pseudomonas syringae and the necrotrophic ascomycete Botrytis cinerea.
      Furthermore, the lif2-1 sid2-2 double mutant was less susceptible than the wild
      type to P. syringae infection, suggesting that the lif2 response to pathogens was
      independent of SA accumulation. Together, our data suggest that lif2-1 exhibits a
      basal primed defense state, resulting from complex deregulation of gene
      expression, which leads to increased resistance to pathogens with various
      infection strategies. Therefore, LIF2 may function as a suppressor of cell
      autonomous immunity. Similar to its human homolog, NSAP1/SYNCRIP, a trans-acting
      factor involved in both cellular processes and the viral life cycle, LIF2 may
      regulate the conflicting aspects of development and defense programs, suggesting
      that a conserved evolutionary trade-off between growth and defense pathways
      exists in eukaryotes. 

PMID- 24914895
TI  - Regulation of plant immunity through modulation of phytoalexin synthesis.
AB  - Soybean hairy roots transformed with the resveratrol synthase and resveratrol
      oxymethyl transferase genes driven by constitutive Arabidopsis actin and CsVMV
      promoters were characterized. Transformed hairy roots accumulated glycoside
      conjugates of the stilbenic compound resveratrol and the related compound
      pterostilbene, which are normally not synthesized by soybean plants. Expression
      of the non-native stilbenic phytoalexin synthesis in soybean hairy roots
      increased their resistance to the soybean pathogen Rhizoctonia solani. The
      expression of the AhRS3 gene resulted in 20% to 50% decreased root necrosis
      compared to that of untransformed hairy roots. The expression of two genes, the
      AhRS3 and ROMT, required for pterostilbene synthesis in soybean, resulted in
      significantly lower root necrosis (ranging from 0% to 7%) in transgenic roots
      than in untransformed hairy roots that had about 84% necrosis. Overexpression of
      the soybean prenyltransferase (dimethylallyltransferase) G4DT gene in soybean
      hairy roots increased accumulation of the native phytoalexin glyceollin resulting
      in decreased root necrosis. 

PMID- 24914896
TI  - Effect of structure on the interactions between five natural antimicrobial
      compounds and phospholipids of bacterial cell membrane on model monolayers.
AB  - Monolayers composed of bacterial phospholipids were used as model membranes to
      study interactions of the naturally occurring phenolic compounds 2,5
      dihydroxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde, and the plant
      essential oil compounds carvacrol, cinnamaldehyde, and geraniol, previously found
      to be active against both Gram-positive and Gram-negative pathogenic
      microorganisms. The lipid monolayers consist of 1,2-dihexadecanoyl-sn-glycero-3
      phosphoethanolamine (DPPE), 1,2-dihexa- decanoyl-sn-glycero-3-phospho-(1'-rac
      glycerol) (DPPG), and 1,1',2,2'-tetratetradecanoyl cardiolipin (cardiolipin).
      Surface pressure-area (pi-A) and surface potential-area (Deltapsi-A) isotherms
      were measured to monitor changes in the thermodynamic and physical properties of
      the lipid monolayers. Results of the study indicated that the five compounds
      modified the three lipid monolayer structures by integrating into the monolayer,
      forming aggregates of antimicrobial -lipid complexes, reducing the packing
      effectiveness of the lipids, increasing the membrane fluidity, and altering the
      total dipole moment in the monolayer membrane model. The interactions of the five
      antimicrobial compounds with bacterial phospholipids depended on both the
      structure of the antimicrobials and the composition of the monolayers. The
      observed experimental results provide insight into the mechanism of the molecular
      interactions between naturally-occurring antimicrobial compounds and
      phospholipids of the bacterial cell membrane that govern activities. 

PMID- 24914897
TI  - Sesamin enhances cholesterol efflux in RAW264.7 macrophages.
AB  - Foam cells formation as a result of the uncontrolled cytophagy of modified
      cholesterol by macrophages plays a key role in the occurrence and development of
      atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has
      been shown to possess multiple pharmacological activities. In this work, we
      investigated the effects of sesamin on foam cell formation and cholesterol efflux
      in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced
      cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol
      (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 MUM) significantly enhanced
      cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime
      quantitative PCR and luciferase assays showed that sesamin significantly
      increased the mRNA levels of PPARgamma, LXRalpha, and ABCG1, and increased the
      transcriptional activity of PPARgamma. The stimulating effect of sesamin on
      cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a
      potent inhibitor of PPARgamma. These results suggest that sesamin is a new
      inhibitor of foam cell formation that may stimulate cholesterol efflux through
      upregulation of the PPARgamma-LXRalpha-ABCG1 pathway. 

PMID- 24914899
TI  - Ampicillin-ester bonded branched polymers: characterization, cyto-, genotoxicity
      and controlled drug-release behaviour.
AB  - The development and characterization of novel macromolecular conjugates of
      ampicillin using branched biodegradable polymers has been described in this
      study. The conjugates have been prepared coupling the beta-lactam antibiotic with
      branched polymer matrices based on the natural oligopeptide core. The cyto- and
      genotoxicity of the synthesized polymers were evaluated with a bacterial
      luminescence test, two protozoan assays and Salmonella typhimurium TA1535. The
      presence of a newly formed covalent bond between the drug and the polymer
      matrices was confirmed by 1H-NMR and FTIR studies. A drug content (15.6 and 10.2
      mole %) in the macromolecular conjugates has been determined. The obtained
      macromolecular products have been subjected to further in vitro release studies.
      The total percentage of ampicillin released after 21 days of incubation was
      nearly 60% and 14% and this resulted from the different physicochemical
      properties of the polymeric matrices. This is the first report on the application
      of branched biodegradable polymeric matrices for the covalent conjugation of
      ampicillin. The obtained results showed that the synthesized macromolecular drug
      conjugates might slowly release the active drug molecule and improve the
      pharmacokinetics of ampicillin. 

PMID- 24914898
TI  - Structural crystalline characterization of sakuranetin--an antimicrobial
      flavanone from twigs of Baccharis retusa (Asteraceae).
AB  - Bioactivity-guided fractionation of an antimicrobial active extract from twigs of
      Baccharis retusa C. DC. (Asteraceae) yielded the flavanone 5,4'-dihydroxy-7
      methoxy-flavanone (sakuranetin) as responsible for the detected activity. The
      structure of the bioactive compound was established on the basis of spectroscopic
      data analysis, including NMR and MS. Additionally, the structure of a new crystal
      form of sakuranetin was confirmed by X-ray diffratometry. The minimum inhibitory
      concentrations (MIC) of isolated compound were determined against pathogenic
      yeast belonging to the genus Candida (six species), Cryptococcus (two
      species/four serotypes) and S. cerevisiae BY 4742 (S288c background) and ranged
      from 0.32 to 0.63 MUg/MUL. Our results showed that sakuranetin, which structure
      was fully characterized, could be used as a tool for the design of novel and more
      efficacious antifungal agents. 

PMID- 24914900
TI  - Effects of fructus psoraleae extract on the intestinal absorption kinetics of
      geniposide and geniposidic acid in rat.
AB  - Cortex Eucommia has been used as a kidney-tonifying herbal medicine with a long
      history of compatibility with Fructus Psoraleae. Geniposide (GP) and geniposidic
      acid (GPA) are the two main chemical components in Cortex Eucommia. In the
      present study, the effects of Fructus Psoraleae extract (FPE) on intestinal
      absorption kinetics of GP and GPA in rat were investigated. Twenty four male
      Sprague-Dawley rats were randomly assigned into four groups which were treated
      with GP, GPA, GP mixed with FPE and GPA mixed with FPE, respectively, by in situ
      intestinal perfusion for 3 h. The samples of intestinal perfusion solutions were
      collected every 30 min, and analyzed by ultra high performance liquid
      chromatography (UPLC). The curves of time and residual quantities of GP and GPA
      (lnx) in the intestinal perfusion solution and the cumulative absorption rate
      were obtained. The results showed that FPE exhibited different effects on the
      intestinal absorption of GP and GPA in rat: it increased the intestinal
      absorption of GP (p<0.05), while demonstrated no significant effect on the
      absorption of GPA.

PMID- 24914901
TI  - Qualitative and quantitative analysis of triterpene saponins from tea seed pomace
      (Camellia oleifera Abel) and their activities against bacteria and fungi.
AB  - A method using LC-ESI-IT-TOF/MS and LC/UV-ELSD was established to qualitatively
      analyze triterpene saponins obtained from the tea seed pomace (Camellia oleifera
      Abel). In addition, the quantitative analysis of oleiferasaponin A1 using LC/UV
      was developed. The purified total saponins did not exhibit any inhibitory effects
      at concentrations ranging from 0.1 to 10 mg/mL against the tested bacteria,
      except for Staphyloccocus aureus and Escherichia coli. By contrast, higher
      inhibitory activity was seen against the tested fungi, especially against
      Bipolaris maydis. Following treatment with an MIC value of 250 MUg/mL for 24 h,
      the mycelial morphology was markedly shriveled in appearance or showed flattened
      and empty hyphae, with fractured cell walls, ruptured plasmalemma and cytoplasmic
      coagulation or leakage. These structural changes hindered the growth of mycelia. 

PMID- 24914902
TI  - Microextraction techniques used in the procedures for determining organomercury
      and organotin compounds in environmental samples.
AB  - Due to human activities, the concentrations of organometallic compounds in all
      parts of the environment have increased in recent decades. The toxicity and some
      biochemical properties of mercury and tin present in the environment depend on
      the concentration and chemical form of these two elements. The ever-increasing
      demand for determining compounds at very low concentration levels in samples with
      complex matrices requires the elimination of interfering substances, the
      reduction of the final extract volume, and analyte enrichment in order to employ
      a detection technique, which is characterised by high sensitivity at low limits
      of quantification. On the other hand, in accordance with current trends, the
      analytical procedures should aim at the miniaturisation and simplification of the
      sample preparation step. In the near future, more importance will be given to the
      fulfilment of the requirements of Green Chemistry and Green Analytical Chemistry
      in order to reduce the intensity of anthropogenic activities related to
      analytical laboratories. In this case, one can consider the use of solvent
      free/solvent-less techniques for sample preparation and microextraction
      techniques, because the use of the latter leads to lowering the quantity of
      reagents used (including solvents) due to the reduction of the scale of analysis.
      This paper presents an overview of microextraction techniques (SPME and LPME)
      used in the procedures for determining different chemical forms of mercury and
      tin. 

PMID- 24914903
TI  - An efficient synthesis of pyridoxal oxime derivatives under microwave
      irradiation.
AB  - Quaternary salts of pyridoxal oxime have been synthesized by the quaternization
      of pyridoxal oxime with substituted phenacyl bromides using microwave heating.
      Microwave-assisted rapid synthesis was done both in solvent (acetone) and under
      solvent-free conditions. Good to excellent yields (58%-94%) were obtained in
      acetone in very short reaction times (3-5 min) as well as in the solvent-free
      procedure (42%-78%) in very short reaction times (7-10 min) too. Effective
      metodologies for the preparation of pyridoxal oxime quaternary salts, having the
      advantagies of being eco-friendly, easy to handle, and performed in shorter
      reactions time are presented. The structure of compound 7, in which a 4
      fluorophenacyl moiety is bonded to the pyridinium ring nitrogen atom, was
      unequivocally confirmed by the single-crystal X-ray diffraction method. 

PMID- 24914904
TI  - Two new lanostane triterpenoids from the branches and leaves of Polyalthia
      oblique.
AB  - Two new lanostane triterpenoids, 20-hydroxyeuphorbol-7-one (1) and 15alpha
      hydroxyeuphorbol-7,11-dione (2), together with four known triterpenoids,
      euphorbol-7-one (3), friedelin (4), stigmast-4-ene-6alpha-ol-3-one (5), stigmasta
      4-en-3,6-dione (6), were isolated from ethanol extract of the branches and leaves
      of Polyalthia obliqua. The structures of 1 and 2 were elucidated on the basis of
      extensive spectroscopic analysis and comparisons with related known compounds.
      Antibacterial activities of two new compounds and four known compounds were
      tested. 

PMID- 24914905
TI  - Module modified acute physiology and chronic health evaluation II: predicting the
      mortality of neuro-critical disease.
AB  - OBJECTIVES: This study aimed to conduct and assess a module modified acute
      physiology and chronic health evaluation (MM-APACHE) II model, based on disease
      categories modified-acute physiology and chronic health evaluation (DCM-APACHE)
      II model, in predicting mortality more accurately in neuro-intensive care units
      (N-ICUs). METHODS: In total, 1686 patients entered into this prospective study.
      Acute physiology and chronic health evaluation (APACHE) II scores of all patients
      on admission and worst 24-, 48-, 72-hour scores were obtained. Neurological
      diagnosis on admission was classified into five categories: cerebral infarction,
      intracranial hemorrhage, neurological infection, spinal neuromuscular (SNM)
      disease, and other neurological diseases. The APACHE II scores of cerebral
      infarction, intracranial hemorrhage, and neurological infection patients were
      used for building the MM-APACHE II model. RESULTS: There were 1386 cases for
      cerebral infarction disease, intracranial hemorrhage disease, and neurological
      infection disease. The logistic linear regression showed that 72-hour APACHE II
      score (Wals  =  173.04, P < 0.001) and disease classification (Wals  =  12.51, P 
      =  0.02) were of importance in forecasting hospital mortality. Module modified
      acute physiology and chronic health evaluation II model, built on the variables
      of the 72-hour APACHE II score and disease category, had good discrimination
      (area under the receiver operating characteristic curve (AU-ROC  =  0.830)) and
      calibration (chi2  =  12.518, P  =  0.20), and was better than the Knaus APACHE
      II model (AU-ROC  =  0.778). DISCUSSION: The APACHE II severity of disease
      classification system cannot provide accurate prognosis for all kinds of the
      diseases. A MM-APACHE II model can accurately predict hospital mortality for
      cerebral infarction, intracranial hemorrhage, and neurologic infection patients
      in N-ICU.

PMID- 24914906
TI  - Clinical characteristics and outcomes of patients with Guillain-Barre and
      acquired CNS demyelinating overlap syndrome: a cohort study based on a literature
      review.
AB  - BACKGROUND: Some patients with Guillain-Barre syndrome (GBS) also have acquired
      demyelination of the central nervous system (CNS) (i.e., acquired demyelinating
      syndrome, ADS). Often, the overlap of GBS and ADS is overlooked. Therefore, we
      evaluated case reports of GBS/ADS overlap syndrome. METHODS: We mainly performed
      website-based research based on articles in cases presented with GBS/ADS overlap
      syndrome. A total of 66 cases were included. Clinical and prognosis data were
      analyzed. RESULTS: A total of 85% of patients with simultaneous or consecutive
      occurrence of GBS and ADS were identified within 4 weeks of the initial
      diagnosis. Transverse myelitis (TM) (32%) was the most common ADS found in
      GBS/ADS. Patients with Miller Fisher syndrome (MFS)/ADS overlap syndrome had
      greater female predominance, mean age, frequency of onset at the same time
      period, or within a short period, and percentage of sole involvement of the
      subtentorial region. The outcome was favorable based on the functional status in
      74% of patients. The sensory level (OR  =  0.182, 95% CI  =  0.055-0.598; P  = 
      0.005) was the best predictor of a poor outcome, while visual deficit (OR  = 
      4.667, 95% CI  =  1.187-18.352; P  =  0.027) predicted a favorable outcome.
      CONCLUSION: The ADS in GBS are diverse, CNS demyelinating may occur at any time,
      but early in the GBS course (and vice versa). MFS/ADS overlap syndromes is more
      common. The prognosis is generally good, but patients with sensory level deficit
      are likely to have a poor prognosis. The features of MFS/other CIS may better
      reflect involvement of the brainstem in MFS itself, rather than ADS in autoimmune
      peripheral neuropathies.

PMID- 24914907
TI  - Controlled early inflammation and bone healing--potential new treatments.

PMID- 24914908
TI  - Zygomatic implants: the impact of zygoma bone support on biomechanics.
AB  - Maxillectomy and severely resorbed maxilla are challenging to restore with
      provision of removable prostheses. Dental implants are essential to restore
      esthetics and function and subsequently quality of life in such group of
      patients. Zygomatic implants reduce the complications associated with bone
      grafting procedures and simplify the rehabilitation of atrophic maxilla and
      maxillectomy. The purpose of this study was to compare, by means of 3-dimensional
      finite element analysis, the impact of different zygomatic bone support (10, 15,
      and 20 mm) on the biomechanics of zygomatic implants. Results indicated that
      maximum stresses within the fixture were increased by 3 times when bone support
      decreased from 20 to 10 mm and were concentrated at the fixture/bone interface.
      However, stresses within the abutment screw and the abutment itself were not
      significantly different regardless of the bone support level. Supporting bone at
      10 mm sustained double the stresses of 15 and 20 mm. Fixture's deflection was
      decreased by 2 to 3 times when bone support level increased to 15 mm and 20 mm,
      respectively. It was concluded that zygomatic bone support should not be less
      than 15 mm, and abutment screw is not at risk of fracture regardless of the
      zygomatic bone support. 

PMID- 24914909
TI  - A comparative study on microgap of premade abutments and abutments cast in base
      metal alloys.
AB  - The study compared the marginal accuracy of premade and cast abutments. Premade
      titanium, stainless steel, and gold abutments formed the control groups. Plastic
      abutments were cast in nickel-chromium, cobalt-chromium and grade IV titanium.
      The abutment/implant interface was analyzed. Analysis of variance and Duncan's
      multiple range test revealed no significant difference in mean marginal microgap
      between premade gold and titanium abutments and between premade stainless steel
      and cast titanium abutments. Statistically significant differences (P < .001)
      were found among all other groups. 

PMID- 24914910
TI  - Topical simvastatin improves the pro-angiogenic and pro-osteogenic properties of
      bioglass putty in the rat calvaria critical-size model.
AB  - Objective was to describe the effect of bioactive glass putty with and without
      topical simvastatin on new bone formation in critical-sized defects of rat
      calvaria. A calvarial bone defect was created in 20 male Wistar rats and filled
      with bioactive glass alone (n = 10) or combined with simvastatin (n = 10). After
      4 weeks, the defects were histomorphometrically evaluated for volume fraction
      (Vv) of woven bone, vessel density, bioglass quantity, and inflammation. Compared
      to the bioglass-only group, rats treated with simvastatin had greater Vv of blood
      vessels (3.3% +/- 0.7 vs 1.6% +/- 0.1, P = .0002) and new bone (2.3% +/- 0.2 vs
      1.8% +/- 2.5, P = .003). The Vv of the bioglass remnants in the bioglass-only
      group was higher than in the group treated with simvastatin (2.4% +/- 0.08 vs
      1.7% +/- 0.3, P < .0004). Chronic inflammation was noted in 1 rat from each
      group. Topical simvastatin seems to improve the pro-angiogenic and pro-osteogenic
      properties of bioglass putty in rat calvaria critical-size defects without
      significant inflammation. 

PMID- 24914911
TI  - Assessment of the correlation between insertion torque and resonance frequency
      analysis of implants placed in bone tissue of different densities.
AB  - The primary stability of dental implants is fundamental for osseointegration.
      Therefore, this study aimed to assess the correlation between insertion torque
      (IT) and resonance frequency analysis (RFA) of implants placed in mandibles and
      maxillas of different bone densities. Eighty dental implants were placed in
      maxillas and mandibles, and IT and the implant stability quotient (ISQ) were
      measured at the time of implant insertion. Bone density was assessed subjectively
      by the Lekholm and Zarb index. The type I and II densities were grouped together
      (group A)as were the type III and IV densities (group B). The IT in group A was
      higher (Student t test, P = .0013) than in group B (46.27 +/- 18.51 Ncm, 33.62 +/
      14.74 Ncm, respectively). The implants placed in group A showed higher ISQ
      (Student t test, P = .0004) than those placed in group B (70.09 +/- 7.50, 63.66
      +/- 8.00, respectively). A significant correlation between IT and the ISQ value
      was observed for group A (Pearson correlation test; r = 0.35; P = .0213) and for
      group B (r = 0.37; P = .0224). Within the limitations of this study, it was
      possible to conclude that there is a correlation between IT and RFA of implants
      placed in mandibles and maxillas of different bone densities. 

PMID- 24914912
TI  - Benefits of rehabilitation with implants in masticatory function: is patient
      perception of change in accordance with the real improvement?
AB  - This study aimed to compare the index of satisfaction and masticatory function of
      edentulous patients before and after rehabilitation and to evaluate if patients'
      perception of the changes in their oral health status is in agreement with the
      results of masticatory performance test. Fourteen edentulous patients were
      rehabilitated with lower implant-supported fixed prosthesis and upper removable
      dentures. Index of satisfaction and masticatory capacity (subjective analysis)
      and performance test (objective analysis) were evaluated before and 20 days and 8
      months after rehabilitation. The patients were asked to respond a yes/no
      masticatory capacity questionnaire and to rate their oral satisfaction on a 0 to
      10 Visual Analogue Scale (VAS). Masticatory performance test comprised the
      ability of the individual to pulverize an artificial test food (Optocal), after
      20 and 40 masticatory strokes. When baseline answers were compared to answers 8
      months after treatment, all questions, excepting the ones that considered pain
      and social disability, were statistically different. Wilcoxon test was used to
      compare index of satisfaction before and after treatment. All answers showed
      statistically significant differences, excluding the one that referred to ease of
      cleaning the prostheses. Considering the masticatory performance test, Student t
      test (normally distributed) and Wilcoxon test (non-normally distributed) were
      used to test the null hypothesis that the weight of the particles of the test
      food left in sieves were equal in all times of evaluation. In the larger sieve
      with 20 cycles, statistically significant differences were observed between
      baseline and 8 months, 20 days and 8 months. With 40 strokes, baseline and 20
      days, baseline and 8 months and 20 days and 8 months showed significant
      differences. It was concluded that oral rehabilitation leads to better
      masticatory function in edentulous patients and there is a coincidence between
      patient perception and real improvement on masticatory function. 

PMID- 24914913
TI  - A method for fabrication of implant-supported fixed partial dentures.
AB  - When restoring a partially edentulous arch with an implant-supported fixed
      partial denture, the optimal fit and function of the final restoration depend on
      the fabrication of an accurate impression and the registration of the
      interocclusal relationship. The present case report presents a method for the
      fabrication of impressions and the registration of the interocclusal relationship
      for implant-supported partial dentures. The described method allows the accurate
      transfer of the implant position and the registration of the interocclusal
      relationship using transfer key and electroformed gold copings. The key and
      copings were used to transfer the intraoral implant position to the cast, to
      position the abutments intraorally, and to facilitate the fabrication of the
      final partial denture. 

PMID- 24914914
TI  - Safe sinus lift: use of acrylic stone trimmer to avoid sinus lining perforation.
AB  - Iatrogenic injury to the maxillary sinus membrane is a common complication during
      direct sinus lift procedures. The most common cause is perforation of the
      Schneiderian membrane using a tungsten-carbide round bur no.6. We propose a safe
      technique in which an acrylic stone trimmer is used to create a window in the
      maxillary antrum thereby minimizing the risk of injury to the delicate sinus
      membrane. 

PMID- 24914915
TI  - The effects of sinus membrane pathology on bone augmentation and procedural
      outcome using minimal invasive antral membrane balloon elevation.
AB  - Membrane pathology tends to complicate the postprocedural course of open sinus
      lift by ostio-meatal complex (OMC) obstruction and consequent acute sinusitis.
      The objective of this study was to evaluate the outcome of subjects with
      considerable sinus membrane pathology undergoing maxillary sinus floor
      augmentation and simultaneous implant placement using the minimal invasive antral
      membrane balloon elevation (MIAMBE) method. This study was a retrospective chart
      review of MIAMBE procedures performed in the presence of significant sinus
      membrane pathology. Sixteen patients with maxillary sinus membrane thickening in
      well-ventilated OMC as determined by dental computerized tomography underwent
      sinus augmentation and simultaneous implant placement using the MIAMBE technique.
      All 16 procedures were successfully concluded without significant procedural or
      postprocedural complications or implant failure. Post MIAMBE membrane pathology
      regressed or disappeared in 8 patients (50%) or remained unchanged in 6 patients
      (37.5%), while in 2 patients the sinus membrane pathology was limited to
      evaluation by periapical X rays. Sinus augmentation using the MIAMBE technique
      can be performed safely in asymptomatic patients in the presence of sinus
      membrane pathology if the OMC is not obstructed. In a significant proportion of
      these cases, complete resolution of the membrane pathology after MIAMBE is
      observed. When compared to open sinus lift, OMC obstruction is less likely to
      occur when employing the MIAMBE method. 

PMID- 24914916
TI  - Cellular responses to metal ions released from implants.
AB  - In the process of calcified tissue formation, cells secrete a protein-rich matrix
      into which they add a metal ion that nucleates in the presence of phosphorus to
      form an inorganic salt (usually calcium hydroxyapatite). Cellular and tissue
      responses to metal ions-released from implants, for example-can therefore be
      considered from the perspective of how cells handle calcium ions. A critical
      factor in determining cellular toxicity will be free ion concentrations and the
      competitive interactions that occur in a physicochemical manner. Three of the
      parameters used to assess the biocompatibility of implant materials are (1) the
      ability to influence mitotic activity, (2) intercellular adhesion, and (3)
      promotion of cell death. A spectrum of responses to free intracellular calcium
      ions can be identified, ranging from presence of the ion being essential for cell
      division through to an excess of the free ion that results in cell death
      (apoptosis). In between these extremes, cells may become postmitotic and express
      phenotypic variations as they adapt to their environment and establish
      equilibrium to maintain intracellular calcium homeostasis. The response of cells
      to implants can be linked to ions released and interactions between these and
      other ions and/or molecules present in the tissues, similar to the manner in
      which cells handle calcium ions. 

PMID- 24914917
TI  - Eight-year follow-up of a fixed-detachable maxillary prosthesis utilizing an
      attachment system: clinical protocol for individuals with skeletal class III
      malocclusions.
AB  - The aim of this article is to describe a successful clinical protocol for
      prosthodontic rehabilitation of a patient with a skeletal Class III malocclusion
      using a fixed-detachable maxillary prosthesis supported by 6 implants and the MK1
      attachment system. The patient was followed up for 8 years. A 46-year-old
      edentulous woman with a skeletal Class III malocclusion expressed dissatisfaction
      with her old existing maxillary denture from an esthetic point of view and
      frustration regarding its function. A fixed-detachable maxillary prosthesis using
      the MK1 attachment system was made. The patient was followed up clinically and
      radiographically for 8 years. No bone loss, fracture of prosthetic components, or
      fracture of the prosthesis was detected in that period. A fixed detachable
      maxillary prosthesis using the MK1 attachment system is a treatment option for
      patients with Class III malocclusions who opt not to undergo orthognathic
      surgery. 

PMID- 24914919
TI  - Flapless implant placement: a case report.
AB  - Full-thickness periosteal flap elevation for implant placement is often
      accompanied by potential marginal bone loss and/or soft tissue recession around
      the implant due to compromised blood supply to underlying bone. To preserve the
      blood supply to underlying bone, implants can be placed with a flapless surgical
      procedure. This procedure also provides numerous other benefits, such as
      decreased trauma, short recovery time, less pain, reduced rate of infection, and
      improved patient compliance. This report presents a case of flapless implant
      placement in the mandibular posterior region that achieved optimum results and
      caused minimal discomfort to the patient. The advantages and limitations of this
      procedure are also discussed. 

PMID- 24914918
TI  - Active implant peri-apical lesion: a case report treated via guided bone
      regeneration with a 5-year clinical and radiographic follow-up.
AB  - Implant peri-apical lesion (IPL) is a periapical lesion, usually asymptomatic, in
      which the coronal portion of the implant achieves a normal bone to implant
      interface. A case of IPL following immediate implant placement and treated with
      guided bone regeneration (GBR) principles is described. Five-year clinical and
      radiographic follow-up with cone-beam assessment showed complete healing of the
      bone. GBR principles applied to IPL could completely solve the lesion. 

PMID- 24914920
TI  - Active implant periapical lesions leading to implant failure: two case reports.
AB  - Implant periapical lesion (IPL), an inflammatory lesion surrounding the apex of a
      dental implant, has been previously reported as a possible cause for implant
      failure. This article describes 2 successive cases of active IPL that were
      diagnosed early by clinical signs and radiologic findings. Lesions were treated
      surgically with implant removal and debridement. The etiology, findings, and
      treatment approaches for IPL are discussed in comparison with other reports. 

PMID- 24914921
TI  - A review of platelet derived growth factor playing pivotal role in bone
      regeneration.
AB  - This article is focused on the literature review and study of recent advances in
      the field of bone grafting, which involves platelet-derived growth factor (PDGF)
      as one of the facilitating factors in bone regeneration. This article includes a
      description of the mechanism of PDGF for use in surgeries where bone grafting is
      required, which promotes future application of PDGF for faster bone regeneration
      or inhibition of bone growth if required as in osteosarcoma. The important
      specific activities of PDGF include mitogenesis (increase in the cell populations
      of healing cells), angiogenesis (endothelial mitoses into functioning
      capillaries), and macrophage activation (debridement of the wound site and a
      second phase source of growth factors for continued repair and bone
      regeneration). Thus PDGF can be utilized in wound with bone defect to conceal the
      wound with repair of bony defect. 

PMID- 24914923
TI  - Identification of three exercise-induced mortality risk factors in patients with
      COPD.
AB  - The survival rate of chronic obstructive pulmonary disease (COPD) patients with
      severely reduced exercise capacity is extremely low. We recently identified three
      life-threatening pathophysiological conditions during cardiopulmonary exercise
      testing (CPET): (1) exercise-induced hypoxemia, (2) sympathetic overactivity, and
      (3) progressive respiratory acidosis at low-intensity exercise. The present
      prospective observation study aimed to determine whether these parameters
      constitute risk factors of mortality in moderate-to-very severe COPD. Ninety-six
      COPD patients were followed-up, monthly, for >3 years. Subsequently, spirometry
      and CPET were performed to examine parameters of exercise-induced hypoxemia
      ([PaO2 slope, mmHg/L . min(-1)] = Decrease in PaO2/DeltaV O2 (Difference in
      DeltaV O2 between at rest and at peak exercise)), progression of acidosis
      ([DeltapH/DeltaV O2,/L . min(-1)] = Decrease in pH/DeltaV O2), and sympathetic
      overactivity ([Deltanorepinephrine (NE)/DeltaV O2, ng/mL/L . min(-1)] = Increase
      in NE/DeltaV O2). Univariate analysis revealed a significant association between
      the three conditions with increased mortality. Kaplan-Meier analysis showed that
      the quartile combining the steepest PaO2 slope (<=-55 mmHg/DeltaV O2 [L/min]),
      steepest decrease in arterial blood pH (<= -1.72/DeltaV O2 [L/min]), and most
      rapid increase in plasma NE level (>= 5.2 ng/VO2 [L/min]) during incremental
      exercise was associated with higher all-cause mortality. These conditions showed
      cumulative effects on COPD patients' survival. Multivariate analyses revealed
      that these three life-threatening factors are also independent predictors of
      mortality based on age, heart rate and PaO2 at rest, body mass index, and forced
      expiratory volume in 1 s. Thus, these new exercise-induced mortality risk factors
      may lead to more efficient pulmonary rehabilitation programs for COPD patients
      based on patient-specific exercise-induced pathophysiological profiles.

PMID- 24914924
TI  - The development of a method for identifying penalty kick strategies in
      association football.
AB  - Penalty takers in association football adopt either a keeper-independent or a
      keeper-dependent strategy, with the benefits of the keeper-independent strategy
      presumed to be greater. Yet, despite its relevance for research and
      practitioners, thus far no method for identifying penalty kick strategies has
      been available. To develop a validated and reliable method, Experiment 1 assessed
      characteristics that observers should use to distinguish the two strategies. We
      asked participants to rate 12 characteristics of pre-recorded clips of kicks of
      penalty takers that used either a keeper-independent or keeper-dependent
      strategy. A logistic regression model identified three variables (attention to
      the goalkeeper, run-up fluency and kicking technique) that in combination
      predicted kick strategy in 92% of the penalties. We used the model in Experiment
      2 to analyse prevalence and efficacy of both the strategies for penalty kicks in
      penalty shoot-outs during FIFA World Cups (1986-2010) and UEFA Football
      Championships (1984-2012). The keeper-independent strategy was used much more
      frequently (i.e., 78-86%) than the keeper-dependent strategy, but successes did
      not differ. Penalty takers should use both the strategies to be less predictable.
      Goalkeepers can use the developed model to improve their chances to succeed by
      adjusting their behaviour to penalty takers' preferred penalty kick strategy.

PMID- 24914925
TI  - Endoscopic submucosal dissection for early gastric neoplasms in elderly patients.
AB  - OBJECTIVE: To retrospectively evaluate the safety and feasibility of endoscopic
      submucosal dissection (ESD) for the treatment of early gastric cancer (EGC) in
      elderly patients >=75 years of age. PATIENTS AND METHODS: One hundred seventy-one
      patients (187 lesions) treated with ESD from January 2010 to September 2013 were
      enrolled in our study. Subjects were classified into two groups: elderly (age
      >=75 years) or non-elderly (age <75 years). Clinicopathological characteristics,
      resectability, curability, complications, rates of local recurrence, and residual
      disease were evaluated. Association of clinicopathological characteristics of the
      lesions with immediate bleeding was analyzed. RESULTS: No significant differences
      in clinical characteristics were observed. The incidences of comorbidity were
      significantly different between the elderly group and the non-elderly group
      (P<.001). Of the elderly patients, 54.3% had two or more underlying diseases
      compared with 18.4% of the non-elderly patients (P<.001). Of the 98.0% of elderly
      patients and 97.1% of younger patients who received en bloc resection, curative
      resection reached 94.1% and 96.3%, respectively. Immediate bleeding occurred in
      15.2% of the elderly group and 4.8% of the non-elderly group (P=.044). Operation
      time differed significantly (P=.039). No apparent discrepancy was observed in
      perforation and delayed bleeding. The differences in the invasion depth were
      considered between the two groups (P=.001). Logistic regression analysis revealed
      that the rate of immediate bleeding was associated with invasion depth (P=.003).
      There were no differences in the follow-up period and rates of local recurrence
      and residual disease. CONCLUSIONS: ESD is safe and feasible for elderly patients
      in the era of a graying population. Higher risk of immediate bleeding and longer
      operation time should be concerned.

PMID- 24914926
TI  - Laparoscopic renal cryoablation versus laparoscopic partial nephrectomy for the
      treatment of small renal masses: a systematic review and meta-analysis of
      comparative studies.
AB  - BACKGROUND: For small renal masses (SRMs), open partial nephrectomy represents
      the therapeutic standard of care, and laparoscopic partial nephrectomy (LPN) has
      provided encouraging outcomes. Laparoscopic renal cryoablation (LRC) could be
      regarded as an alternative to surgical excision in selected patients, if
      perioperative complication rates and oncologic results are comparable. However,
      the short- and long-term outcomes of LRC versus LPN have not been adequately
      assessed. This study evaluated the safety and efficacy of LRC compared with LPN
      in the treatment of SRMs. MATERIALS AND METHODS: A systematic search of the
      Medline, Scopus, and CNKI databases and the Cochrane Library was performed up to
      October 1, 2013. Outcomes of interest assessing the two techniques included
      demographic and clinical baseline characteristics, surgical and oncological
      variables, renal function, and complications. RESULTS: Nine eligible trials (555
      cases and 642 controls) assessing LRC versus LPN were identified, including two
      prospective and seven retrospective studies. Patients undergoing LRC were
      significantly older (weighted mean difference [WMD], 6.48 years; 95% confidence
      interval [CI], 3.12-9.83; P<.001) and had a higher solitary kidney rate (odds
      ratio [OR]=3.76; 95% CI, 2.05-6.92; P<.001). Although LRC was associated with
      shorter operative time (WMD, -54.28 minutes; 95% CI, -83.79 to -24.78; P<.001),
      less blood loss (WMD, -111.75 mL; 95% CI, -147.96 to -75.53; P<.001), lower risk
      of conversion (OR=0.17; 95% CI, 0.05-0.60; P=.005), and fewer overall
      complications (OR=0.53; 95% CI, 0.29-0.98; P=.04), especially the rate of
      intraoperative complications (OR=0.20; 95% CI, 0.07-0.58; P=.003) and major
      complications (OR=0.45; 95% CI, 0.25-0.81; P=.008), patients having LPN might
      still benefit from a significantly lower local recurrence rate (OR=13.03; 95% CI,
      4.20-40.39; P<.001) and lower distant metastasis rate (OR=9.05; 95% CI, 2.31
      35.51; P=.002). CONCLUSIONS: Compared with LPN, LRC was associated with reliable
      perioperative safety, comparable renal function, and fewer complications;
      however, LRC may still result in a higher risk of tumor progression. Therefore,
      our meta-analysis suggested that LRC was associated with worse oncological
      outcomes than LPN but that LRC may be indicated in selected patients with
      significant comorbidity. Because of the inherent limitations of the included
      studies, further large sample, prospective, multicenter, and long-term follow-up
      studies are awaited to corroborate these findings.

PMID- 24914928
TI  - Responses of reactive oxygen scavenging enzymes, proline and malondialdehyde to
      water deficits among six secondary successional seral species in Loess Plateau.
AB  - Drought can impact local vegetation dynamics in a long term. In order to predict
      the possible successional pathway of local community under drought, the responses
      of some drought resistance indices of six successional seral species in the semi
      arid Loss Hilly Region of China were illustrated and compared on three levels of
      soil water deficits along three growing months (7, 8 and 9). The results showed
      that: 1) the six species had significant differences in SOD, POD activities and
      MDA content. The rank correlations between SOD, POD activities and the
      successional niche positions of the six species were positive, and the
      correlation between MDA content and the niche positions was negative; 2)
      activities of SOD, CAT and POD, and content of proline and MDA had significant
      differences among the three months; 3) there existed significant interactions of
      SOD, CAT, POD activities and MDA content between months and species. With an
      exception, no interaction of proline was found. Proline in leaves had a general
      decline in reproductive month; 4) SOD, CAT, POD activities and proline content
      had negative correlations with MDA content. Among which, the correlation between
      SOD activity and MDA content was significant. The results implied that, in arid
      or semiarid region, the species at later successional stage tend to have strong
      drought resistance than those at early stage. Anti-drought indices can partially
      interpret the pathway of community succession in the drought impacted area. SOD
      activity is more distinct and important on the scope of protecting membrane
      damage through the scavenging of ROS on exposure to drought. 

PMID- 24914929
TI  - Sex-specific interactions of microbial symbioses on cricket dietary selection.
AB  - The nutrients found in prey and nonprey foods, and relative digestibility of
      these foods, has a major influence on diet selection by omnivorous insects. Many
      insects have developed symbiotic relationships with gut bacteria to help with
      extracting nutrition from nonprey diets. Gryllus pennsylvanicus (Burmeister)
      (Orthoptera: Gryllidae) was assigned to one of two treatment groups, antibiotic
      treated and nonantibiotic-treated, and consumption of seeds (nonprey) and eggs
      (prey) were measured. Male crickets administered antibiotics consumed more seeds
      and greater seed weight, while antibiotic-fed female crickets consumed fewer
      seeds and less seed weight, relative to the untreated male and female crickets,
      respectively. Both male and female antibiotic-treated crickets consumed similar
      weight of eggs as nonantibiotic-treated male and female crickets, respectively.
      These results provide evidence that gut symbionts influence diet selection of
      male and female G. pennsylvanicus differently. This sex-specific dietary
      selection may be because of the fact that male and female crickets have different
      nutritional requirements. 

PMID- 24914930
TI  - Identifying significant and relevant events during pediatric transport: a
      modified Delphi study.
AB  - OBJECTIVES: Children must often be transported to dedicated pediatric centers to
      receive specialized medical and surgical care, which places them at risk for
      significant deterioration and life-threatening events. Studies designed to
      identify and mitigate these events have been limited by variability in the
      selection and definition of significant events. The objective of this study was
      to identify and evaluate indicators that represent significant events during the
      transport of pediatric patients and are relevant to future research initiatives
      in transport medicine. DESIGN: We conducted a modified Delphi study consisting of
      four iterations. SETTING: The expert panel included Canadian, interdisciplinary
      healthcare providers with transport experience. INTERVENTIONS: In the first
      Delphi iteration, experts suggested indicators for consideration and evaluated
      proposed indicators from the literature and introduced by the study steering
      committee. In subsequent iterations, respondents reevaluated all indicators that
      had not yet achieved a priori-defined consensus; group comments and aggregate
      scores for each indicator from previous iterations were provided. MEASUREMENTS
      AND MAIN RESULTS: The expert panel consisted of 16 physicians and 17 nonphysician
      healthcare providers from 10 Canadian institutions. In total, the panel evaluated
      57 indicators, including 26 not previously presented in the literature. The
      expert panel determined 52 were significant and relevant to future studies in
      pediatric transport. The final indicator list includes trigger tools
      (interventions, physiological markers, and laboratory values) and team member
      safety and process issues. CONCLUSIONS: Using a systematic, modified Delphi
      approach, we developed an inclusive list of indicators for application to
      pediatric transport-related quality improvement and clinical research projects.

PMID- 24914927
TI  - Age-dependent transcriptome and proteome following transection of neonatal spinal
      cord of Monodelphis domestica (South American grey short-tailed opossum).
AB  - This study describes a combined transcriptome and proteome analysis of
      Monodelphis domestica response to spinal cord injury at two different postnatal
      ages. Previously we showed that complete transection at postnatal day 7 (P7) is
      followed by profuse axon growth across the lesion with near-normal locomotion and
      swimming when adult. In contrast, at P28 there is no axon growth across the
      lesion, the animals exhibit weight-bearing locomotion, but cannot use hind limbs
      when swimming. Here we examined changes in gene and protein expression in the
      segment of spinal cord rostral to the lesion at 24 h after transection at P7 and
      at P28. Following injury at P7 only forty genes changed (all increased
      expression); most were immune/inflammatory genes. Following injury at P28 many
      more genes changed their expression and the magnitude of change for some genes
      was strikingly greater. Again many were associated with the immune/inflammation
      response. In functional groups known to be inhibitory to regeneration in adult
      cords the expression changes were generally muted, in some cases opposite to that
      required to account for neurite inhibition. For example myelin basic protein
      expression was reduced following injury at P28 both at the gene and protein
      levels. Only four genes from families with extracellular matrix functions thought
      to influence neurite outgrowth in adult injured cords showed substantial changes
      in expression following injury at P28: Olfactomedin 4 (Olfm4, 480 fold compared
      to controls), matrix metallopeptidase (Mmp1, 104 fold), papilin (Papln, 152 fold)
      and integrin alpha4 (Itga4, 57 fold). These data provide a resource for
      investigation of a priori hypotheses in future studies of mechanisms of spinal
      cord regeneration in immature animals compared to lack of regeneration at more
      mature stages. 

PMID- 24914931
TI  - CD4(+) T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in
      SHIV-infected Rhesus Macaques.
AB  - MazF, an endoribonuclease encoded by Escherichia coli, specifically cleaves the
      ACA (adenine-cytosine-adenine) sequence of single-stranded RNAs. Conditional
      expression of MazF under the control of the HIV-1 LTR promoter rendered CD4(+) T
      cells resistant to HIV-1 replication without affecting cell growth. To
      investigate the safety, persistence and efficacy of MazF-modified CD4(+) T cells
      in a nonhuman primate model in vivo, rhesus macaques were infected with a
      pathogenic simian/human immunodeficiency virus (SHIV) and transplanted with
      autologous MazF-modified CD4(+) T cells. MazF-modified CD4(+) T cells were
      clearly detected throughout the experimental period of more than 6 months. The
      CD4(+) T cell count values increased in all four rhesus macaques. Moreover, the
      transplantation of the MazF-modified CD4(+) T cells was not immunogenic, and did
      not elicit cellular or humoral immune responses. These data suggest that the
      autologous transplantation of MazF-modified CD4(+) T cells in the presence of
      SHIV is effective, safe and not immunogenic, indicating that this is an
      attractive strategy for HIV-1 gene therapy. 

PMID- 24914932
TI  - Liver resection in hepatitis B-related hepatocellular carcinoma: clinical
      outcomes and safety in overweight and obese patients.
AB  - OBJECTIVE AND BACKGROUND: Although many studies on evaluating the safety of liver
      resection in obese patients have been conducted, the results remain
      contradictory. The aim of our study was to investigate the safety of overweight
      and obese patients undergoing liver resection for hepatitis B-related
      hepatocellular carcinoma in a large sample. METHODS: In a retrospective cohort
      with 1543 hepatitis B-related hepatocellular carcinoma patients, the subjects
      were stratified into four groups according to their body mass index(BMI):
      obesity(BMI>=28), overweight(BMI:24.0-27.9), normal weight(BMI:18.5-23.9) and
      underweight(BMI<18.5). The Dindo-Clavien classification system was used for
      grading complications. Clinical characteristics and operative outcomes were
      compared among the four groups. Risk factors for postoperative complications were
      evaluated by multivariate analysis. RESULTS: According to the category criteria
      of the Working Group on Obesity in China (WGOC) criteria, 73(4.7%) obese,
      412(26.7%) overweight, 982(63.6%) normal weight and 76(4.9%) underweight patients
      were included in our cohort. Overweight and obese patients had more preoperative
      comorbidities such as hypertension(P<0.001). Mortality, total complications and
      complications classified by Clavien system were similar among the four groups
      except that the underweight patients had fewer total complications. However,
      postoperative wound complication was more common in overweight and obese
      patients(6.3% vs 2.5%,P<0.001,11.0% vs 2.5%,P = 0.001). Multivariate analysis
      revealed that BMI was not an independently significant factor for postoperative
      complications. CONCLUSIONS: Liver resection for obese and overweight patients is
      safe and BMI itself is not a risk factor for mortality and morbidity.

PMID- 24914934
TI  - Trophic scaling and occupancy analysis reveals a lion population limited by top
      down anthropogenic pressure in the Limpopo National Park, Mozambique.
AB  - The African lion (Panthera Leo) has suffered drastic population and range
      declines over the last few decades and is listed by the IUCN as vulnerable to
      extinction. Conservation management requires reliable population estimates,
      however these data are lacking for many of the continent's remaining populations.
      It is possible to estimate lion abundance using a trophic scaling approach.
      However, such inferences assume that a predator population is subject only to
      bottom-up regulation, and are thus likely to produce biased estimates in systems
      experiencing top-down anthropogenic pressures. Here we provide baseline data on
      the status of lions in a developing National Park in Mozambique that is impacted
      by humans and livestock. We compare a direct density estimate with an estimate
      derived from trophic scaling. We then use replicated detection/non-detection
      surveys to estimate the proportion of area occupied by lions, and hierarchical
      ranking of covariates to provide inferences on the relative contribution of prey
      resources and anthropogenic factors influencing lion occurrence. The direct
      density estimate was less than 1/3 of the estimate derived from prey resources
      (0.99 lions/100 km2 vs. 3.05 lions/100 km2). The proportion of area occupied by
      lions was Psi = 0.439 (SE = 0.121), or approximately 44% of a 2,400 km2 sample of
      potential habitat. Although lions were strongly predicted by a greater
      probability of encountering prey resources, the greatest contributing factor to
      lion occurrence was a strong negative association with settlements. Finally, our
      empirical abundance estimate is approximately 1/3 of a published abundance
      estimate derived from opinion surveys. Altogether, our results describe a lion
      population held below resource-based carrying capacity by anthropogenic factors
      and highlight the limitations of trophic scaling and opinion surveys for
      estimating predator populations exposed to anthropogenic pressures. Our study
      provides the first empirical quantification of a population that future change
      can be measured against.

PMID- 24914933
TI  - Identification of continuous human B-cell epitopes in the VP35, VP40,
      nucleoprotein and glycoprotein of Ebola virus.
AB  - Ebola virus (EBOV) is a highly virulent human pathogen. Recovery of infected
      patients is associated with efficient EBOV-specific immunoglobulin G (IgG)
      responses, whereas fatal outcome is associated with defective humoral immunity.
      As B-cell epitopes on EBOV are poorly defined, we sought to identify specific
      epitopes in four EBOV proteins (Glycoprotein (GP), Nucleoprotein (NP), and matrix
      Viral Protein (VP)40 and VP35). For the first time, we tested EBOV IgG+ sera from
      asymptomatic individuals and symptomatic Gabonese survivors, collected during the
      early humoral response (seven days after the end of symptoms) and the late memory
      phase (7-12 years post-infection). We also tested sera from EBOV-seropositive
      patients who had never had clinical signs of hemorrhagic fever or who lived in
      non-epidemic areas (asymptomatic subjects). We found that serum from asymptomatic
      individuals was more strongly reactive to VP40 peptides than to GP, NP or VP35.
      Interestingly, anti-EBOV IgG from asymptomatic patients targeted three
      immunodominant regions of VP40 reported to play a crucial role in virus assembly
      and budding. In contrast, serum from most survivors of the three outbreaks,
      collected a few days after the end of symptoms, reacted mainly with GP peptides.
      However, in asymptomatic subjects the longest immunodominant domains were
      identified in GP, and analysis of the GP crystal structure revealed that these
      domains covered a larger surface area of the chalice bowl formed by three GP1
      subunits. The B-cell epitopes we identified in the EBOV VP35, VP40, NP and GP
      proteins may represent important tools for understanding the humoral response to
      this virus and for developing new antibody-based therapeutics or detection
      methods. 

PMID- 24914935
TI  - A change in liver metabolism but not in brown adipose tissue thermogenesis is an
      early event in ovariectomy-induced obesity in rats.
AB  - Menopause is associated with increased visceral adiposity and disrupted glucose
      homeostasis, but the underlying molecular mechanisms related to these metabolic
      changes are still elusive. Brown adipose tissue (BAT) plays a key role in energy
      expenditure that may be regulated by sexual steroids, and alterations in glucose
      homeostasis could precede increased weight gain after ovariectomy. Thus, the aim
      of this work was to evaluate the metabolic pathways in both the BAT and the liver
      that may be disrupted early after ovariectomy. Ovariectomized (OVX) rats had
      increased food efficiency as early as 12 days after ovariectomy, which could not
      be explained by differences in feces content. Analysis of isolated BAT
      mitochondria function revealed no differences in citrate synthase activity,
      uncoupling protein 1 expression, oxygen consumption, ATP synthesis, or heat
      production in OVX rats. The addition of GDP and BSA to inhibit uncoupling protein
      1 decreased oxygen consumption in BAT mitochondria equally in both groups. Liver
      analysis revealed increased triglyceride content accompanied by decreased levels
      of phosphorylated AMP-activated protein kinase and phosphorylated acetyl-CoA
      carboxylase in OVX animals. The elevated expression of gluconeogenic enzymes in
      OVX and OVX + estradiol rats was not associated with alterations in glucose
      tolerance test or in serum insulin but was coincident with higher glucose
      disposal during the pyruvate tolerance test. Although estradiol treatment
      prevented the ovariectomy-induced increase in body weight and hepatic
      triglyceride and cholesterol accumulation, it was not able to prevent increased
      gluconeogenesis. In conclusion, the disrupted liver glucose homeostasis after
      ovariectomy is neither caused by estradiol deficiency nor is related to increased
      body mass. 

PMID- 24914936
TI  - Thyroid hormone receptor alpha mutation causes a severe and thyroxine-resistant
      skeletal dysplasia in female mice.
AB  - A new genetic disorder has been identified that results from mutation of THRA,
      encoding thyroid hormone receptor alpha1 (TRalpha1). Affected children have a
      high serum T3:T4 ratio and variable degrees of intellectual deficit and
      constipation but exhibit a consistently severe skeletal dysplasia. In an attempt
      to improve developmental delay and alleviate symptoms of hypothyroidism, patients
      are receiving varying doses and durations of T4 treatment, but responses have
      been inconsistent so far. Thra1(PV/+) mice express a similar potent dominant
      negative mutant TRalpha1 to affected individuals, and thus represent an excellent
      disease model. We hypothesized that Thra1(PV/+) mice could be used to predict the
      skeletal outcome of human THRA mutations and determine whether prolonged
      treatment with a supraphysiological dose of T4 ameliorates the skeletal
      abnormalities. Adult female Thra1(PV/+) mice had short stature, grossly abnormal
      bone morphology but normal bone strength despite high bone mass. Although T4
      treatment suppressed TSH secretion, it had no effect on skeletal maturation,
      linear growth, or bone mineralization, thus demonstrating profound tissue
      resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally
      increased bone stiffness and strength, suggesting the potential for detrimental
      consequences in the long term. Our studies establish that TRalpha1 has an
      essential role in the developing and adult skeleton and predict that patients
      with different THRA mutations will display variable responses to T4 treatment,
      which depend on the severity of the causative mutation. 

PMID- 24914937
TI  - Hypothalamic molecular changes underlying natural reproductive senescence in the
      female rat.
AB  - The role of the hypothalamus in female reproductive senescence is unclear. Here
      we identified novel molecular neuroendocrine changes during the natural
      progression from regular reproductive cycles to acyclicity in middle-aged female
      rats, comparable with the perimenopausal progression in women. Expression of 48
      neuroendocrine genes was quantified within three hypothalamic regions: the
      anteroventral periventricular nucleus, the site of steroid positive feedback onto
      GnRH neurons; the arcuate nucleus (ARC), the site of negative feedback and
      pulsatile GnRH release; and the median eminence (ME), the site of GnRH secretion.
      Surprisingly, the majority of changes occurred in the ARC and ME, with few
      effects in anteroventral periventricular nucleus. The overall pattern was
      increased mRNA levels with chronological age and decreases with reproductive
      cycle status in middle-aged rats. Affected genes included transcription factors
      (Stat5b, Arnt, Ahr), sex steroid hormone receptors (Esr1, Esr2, Pgr, Ar),
      steroidogenic enzymes (Sts, Hsd17b8), growth factors (Igf1, Tgfa), and
      neuropeptides (Kiss1, Tac2, Gnrh1). Bionetwork analysis revealed region-specific
      correlations between genes and hormones. Immunohistochemical analyses of
      kisspeptin and estrogen receptor-alpha in the ARC demonstrated age-related
      decreases in kisspeptin cell numbers as well as kisspeptin-estrogen receptor
      alpha dual-labeled cells. Taken together, these results identify unexpectedly
      strong roles for the ME and ARC during reproductive decline and highlight
      fundamental differences between middle-aged rats with regular cycles and all
      other groups. Our data provide evidence of decreased excitatory stimulation and
      altered hormone feedback with aging and suggest novel neuroendocrine pathways
      that warrant future study. Furthermore, these changes may impact other
      neuroendocrine systems that undergo functional declines with age. 

PMID- 24914938
TI  - Macrophage metalloelastase (MMP12) regulates adipose tissue expansion, insulin
      sensitivity, and expression of inducible nitric oxide synthase.
AB  - Macrophage metalloelastase, a matrix metallopeptidase (MMP12) predominantly
      expressed by mature tissue macrophages, is implicated in pathological processes.
      However, physiological functions for MMP12 have not been described. Because mRNA
      levels for the enzyme increase markedly in adipose tissue of obese mice, we
      investigated the role of MMP12 in adipose tissue expansion and insulin
      resistance. In humans, MMP12 expression correlated positively and significantly
      with insulin resistance, TNF-alpha expression, and the number of CD14(+)CD206(+)
      macrophages in adipose tissue. MMP12 was the most abundant matrix
      metallopeptidase detected by proteomic analysis of conditioned medium of M2
      macrophages and dendritic cells. In contrast, it was detected only at low levels
      in bone marrow derived macrophages and M1 macrophages. When mice received a high
      fat diet, adipose tissue mass increased and CD11b(+)F4/80(+)CD11c(-) macrophages
      accumulated to a greater extent in MMP12-deficient (Mmp12(-/-)) mice than in wild
      type mice (Mmp12(+/+)). Despite being markedly more obese, fat-fed Mmp12(-/-)
      mice were more insulin sensitive than fat-fed Mmp12(+/+) mice. Expression of
      inducible nitric oxide synthase (Nos2) by Mmp12(-/-) macrophages was
      significantly impaired both in vivo and in vitro, suggesting that MMP12 might
      mediate nitric oxide production during inflammation. We propose that MMP12 acts
      as a double-edged sword by promoting insulin resistance while combatting adipose
      tissue expansion.

PMID- 24914939
TI  - FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice.
AB  - Lactation is associated with significant alterations in both body composition and
      bone mass. Systemic and local skeletal factors such as receptor activator of
      nuclear factor kappa-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known
      to regulate bone remodeling during and after lactation. Fibroblast growth factor
      21 (FGF-21) may function as an endocrine factor to regulate body composition
      changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In
      this study, we hypothesized that the metabolic changes during lactation were due
      in part to increased circulating FGF-21, which in turn could accentuate bone
      loss. We longitudinally characterized body composition in C57BL/6J (B6) mice
      during (day 7 and day 21 of lactation) and after normal lactation (day 21
      postlactation). At day 7 of lactation, areal bone density declined by 10% (P <
      .001), bone resorption increased (P < .0001), percent fat decreased by 20%,
      energy expenditure increased (P < .01), and markers of brown-like adipogenesis
      were suppressed in the inguinal depot and in preformed brown adipose tissue. At
      day 7 of lactation there was a 2.4-fold increase in serum FGF-21 vs baseline (P <
      .0001), a 8-fold increase in hepatic FGF-21 mRNA (P < .03), a 2-fold increase in
      undercarboxylated osteocalcin (Glu13 OCn) (P < .01), and enhanced insulin
      sensitivity. Recovery of total areal bone density was noted at day 21 of
      lactation, whereas the femoral trabecular bone volume fraction was still reduced
      (P < .01). Because FGF-21 levels rose rapidly at day 7 of lactation in B6
      lactating mice, we next examined lactating mice with a deletion in the Fgf21
      gene. Trabecular and cortical bone masses were maintained throughout lactation in
      FGF-21(-/-) mice, and pup growth was normal. Compared with lactating control
      mice, lactating FGF-21(-/-) mice exhibited an increase in bone formation, but no
      change in bone resorption. In conclusion, in addition to changes in calciotropic
      hormones, systemic FGF-21 plays a role in skeletal remodeling and changes in body
      composition during lactation in B6 mice. 

PMID- 24914940
TI  - Chondrocytes play a major role in the stimulation of bone growth by thyroid
      hormone.
AB  - Thyroid hormone (T3) is required for postnatal skeletal growth. It exerts its
      effect by binding to nuclear receptors, TRs including TRalpha1 and TRbeta1, which
      are present in most cell types. These cell types include chondrocytes and
      osteoblasts, the interactions of which are known to regulate endochondral bone
      formation. In order to analyze the respective functions of T3 stimulation in
      chondrocytes and osteoblasts during postnatal growth, we use Cre/loxP
      recombination to express a dominant-negative TRalpha1(L400R) mutant receptor in a
      cell-specific manner. Phenotype analysis revealed that inhibiting T3 response in
      chondrocytes is sufficient to reproduce the defects observed in hypothyroid mice,
      not only for cartilage maturation, but also for ossification and mineralization.
      TRalpha1(L400R) in chondrocytes also results in skull deformation. In the
      meantime, TRalpha1(L400R) expression in mature osteoblasts has no visible effect.
      Transcriptome analysis identifies a number of changes in gene expression induced
      by TRalpha1(L400R) in cartilage. These changes suggest that T3 normally cross
      talks with several other signaling pathways to promote chondrocytes
      proliferation, differentiation, and skeletal growth. 

PMID- 24914941
TI  - Impact of diet-induced obesity on intestinal stem cells: hyperproliferation but
      impaired intrinsic function that requires insulin/IGF1.
AB  - Nutrient intake regulates intestinal epithelial mass and crypt proliferation.
      Recent findings in model organisms and rodents indicate nutrient restriction
      impacts intestinal stem cells (ISC). Little is known about the impact of diet
      induced obesity (DIO), a model of excess nutrient intake on ISC. We used a Sox9
      EGFP reporter mouse to test the hypothesis that an adaptive response to DIO or
      associated hyperinsulinemia involves expansion and hyperproliferation of ISC. The
      Sox9-EGFP reporter mouse allows study and isolation of ISC, progenitors, and
      differentiated lineages based on different Sox9-EGFP expression levels. Sox9-EGFP
      mice were fed a high-fat diet for 20 weeks to induce DIO and compared with
      littermates fed low-fat rodent chow. Histology, fluorescence activated cell
      sorting, and mRNA analyses measured impact of DIO on jejunal crypt-villus
      morphometry, numbers, and proliferation of different Sox9-EGFP cell populations
      and gene expression. An in vitro culture assay directly assessed functional
      capacity of isolated ISC. DIO mice exhibited significant increases in body
      weight, plasma glucose, insulin, and insulin-like growth factor 1 (IGF1) levels
      and intestinal Igf1 mRNA. DIO mice had increased villus height and crypt density
      but decreased intestinal length and decreased numbers of Paneth and goblet cells.
      In vivo, DIO resulted in a selective expansion of Sox9-EGFP(Low) ISC and
      percentage of ISC in S-phase. ISC expansion significantly correlated with plasma
      insulin levels. In vitro, isolated ISC from DIO mice formed fewer enteroids in
      standard 3D Matrigel culture compared to controls, indicating impaired ISC
      function. This decreased enteroid formation in isolated ISC from DIO mice was
      rescued by exogenous insulin, IGF1, or both. We conclude that DIO induces
      specific increases in ISC and ISC hyperproliferation in vivo. However, isolated
      ISC from DIO mice have impaired intrinsic survival and growth in vitro that can
      be rescued by exogenous insulin or IGF1. 

PMID- 24914943
TI  - Differentially regulated protein kinase A (PKA) activity in adipose tissue and
      liver is associated with resistance to diet-induced obesity and glucose
      intolerance in mice that lack PKA regulatory subunit type IIalpha.
AB  - The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed
      and has a central role in regulating cellular metabolism in all organ systems
      affected by obesity. PKA has four regulatory (RIalpha, RIIalpha, RIbeta, RIIbeta)
      and four catalytic (Calpha, Cbeta, Cgamma, Prkx) subunit isoforms that have
      tissue-specific expression profiles. In mice, knockout (KO) of RIIbeta, the
      primary PKA regulatory subunit in adipose tissue or knockout of the catalytic
      subunit Cbeta resulted in a lean phenotype that resists diet-induced obesity and
      associated metabolic complications. Here we report that the disruption of the
      ubiquitously expressed PKA RIIalpha subunit in mice (RIIalphaKO) confers
      resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis.
      After 2-week high-fat diet exposure, RIIalphaKO mice weighed less than wild-type
      littermates. Over time this effect was more pronounced in female mice that were
      also leaner than their wild-type counterparts, regardless of the diet. Decreased
      intake of a high-fat diet contributed to the attenuated weight gain in RIIalphaKO
      mice. Additionally, RIIalpha deficiency caused differential regulation of PKA in
      key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and
      increased in gonadal adipose tissue. We conclude that RIIalpha represents a
      potential target for therapeutic interventions in obesity, glucose intolerance,
      and nonalcoholic fatty liver disease. 

PMID- 24914942
TI  - Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice:
      a combined immunohistochemical and magnetic resonance imaging study.
AB  - Gliosis, the activation of astrocyte and microglial cell populations, is a
      hallmark of central nervous system injury and is detectable using either
      immunohistochemistry or in vivo magnetic resonance imaging (MRI). Obesity in
      rodents and humans is associated with gliosis of the arcuate nucleus, a key
      hypothalamic region for the regulation of energy homeostasis and adiposity, but
      whether this response is permanent or reversible is unknown. Here we combine
      terminal immunohistochemistry analysis with serial, noninvasive MRI to
      characterize the progression and reversibility of hypothalamic gliosis in high
      fat diet (HFD)-fed mice. The effects of HFD feeding for 16 weeks to increase body
      weight and adiposity relative to chow were nearly normalized after the return to
      chow feeding for an additional 4 weeks in the diet-reversal group. Mice
      maintained on the HFD for the full 20-week study period experienced continued
      weight gain associated with the expected increases of astrocyte and microglial
      activation in the arcuate nucleus, but these changes were not observed in the
      diet-reversal group. The proopiomelanocortin neuron number did not differ between
      groups. Although MRI demonstrated a positive correlation between body weight,
      adiposity, and the gliosis-associated T2 signal in the mediobasal hypothalamus,
      it did not detect the reversal of gliosis among the HFD-fed mice after the return
      to chow diet. We conclude that hypothalamic gliosis associated with 16-week HFD
      feeding is largely reversible in rodents, consistent with the reversal of the HFD
      induced obesity phenotype, and extend published evidence regarding the utility of
      MRI as a tool for studying obesity-associated hypothalamic gliosis in vivo. 

PMID- 24914944
TI  - BK channels regulate myometrial contraction by modulating nuclear translocation
      of NF-kappaB.
AB  - The large-conductance Ca(2+)-activated K(+) (BK) channel plays an essential role
      in maintaining uterine quiescence during pregnancy. Growing evidence has shown a
      link between the BK channel and bacterial lipopolysaccharide (LPS)-induced
      nuclear factor-kappaB (NF-kappaB) activation in macrophages. In the uterus, NF
      kappaB activation plays an important role in inflammatory processes that lead to
      parturition. Our objective was to determine whether the BK channel regulates
      uterine contraction, in part, by modulating NF-kappaB translocation into the
      nucleus. We compared the effects of BK channel modulation to those of LPS on NF
      kappaB nuclear translocation and contraction in an immortalized human myometrial
      cell line (human telomerase reverse transcriptase [hTERT]) and uterine myocytes.
      Our results showed that BK channel inhibitors paxilline and penitrem A induced
      translocation of NF-kappaB into the nucleus in both hTERT cells and uterine
      myocytes to a similar extent as LPS treatment, and LPS and paxilline similarly
      reduced BK channel currents. Conversely, neither BK channel openers nor blockade
      of the small conductance Ca(2+)-activated K(+) channel protein 3 had an effect on
      NF-kappaB translocation. Additionally, collagen-based assays showed that
      paxilline induced contraction of hTERT cells and uterine myocytes. This was
      dependent upon cyclooxygenase-2 activity. Moreover, paxilline-induced
      contractility and increased cyclooxygenase-2 expression both depended on
      availability of free NF-kappaB. This study suggests that BK channels regulate
      myometrial contraction, in part, by modulating nuclear translocation of NF
      kappaB. 

PMID- 24914945
TI  - Region-specific neural corticosterone patterns differ from plasma in a male
      songbird.
AB  - The adrenal hormone corticosterone (CORT) acts on brain to mediate physiology and
      behavior. In songbirds, behavioral effects of CORT vary across species,
      environmental conditions, and life history stage, with several mechanisms
      proposed to account for these divergent results. Although blood CORT levels are
      well characterized, few studies measure CORT within the brain itself. Here we
      used in vivo microdialysis to measure CORT in two regions of the zebra finch
      brain, the hippocampus (HP) and caudal nidopallium (cNp). Our results show that
      we can successfully measure physiological levels of CORT in brain within 15- to
      30-minute intervals of dialysate collection. Moreover, we found that levels in
      the cNp were generally lower than levels in the HP. Surprisingly, whereas plasma
      CORT levels increased in response to a standard stressor, no stress-induced surge
      was detected in the HP or cNp. In addition, although a diel CORT rhythm was
      observed in plasma, the rhythm in brain was attenuated and only observed when
      levels were integrated over a 4-hour time period. Regional differences in brain
      CORT levels were reflected in local mRNA expression levels of the CORT
      inactivating enzyme 11beta-hydroxysteroid dehydrogenase type 2 with levels
      elevated in the cNp relative to the HP. Region-specific CORT metabolism may
      therefore play a role in buffering the brain from CORT fluctuations. 

PMID- 24914946
TI  - Ground reaction force estimates from ActiGraph GT3X+ hip accelerations.
AB  - Simple methods to quantify ground reaction forces (GRFs) outside a laboratory
      setting are needed to understand daily loading sustained by the body. Here, we
      present methods to estimate peak vertical GRF (pGRFvert) and peak braking GRF
      (pGRFbrake) in adults using raw hip activity monitor (AM) acceleration data. The
      purpose of this study was to develop a statistically based model to estimate
      pGRFvert and pGRFbrake during walking and running from ActiGraph GT3X+ AM
      acceleration data. 19 males and 20 females (age 21.2 +/- 1.3 years, height 1.73
      +/- 0.12 m, mass 67.6 +/- 11.5 kg) wore an ActiGraph GT3X+ AM over their right
      hip. Six walking and six running trials (0.95-2.19 and 2.20-4.10 m/s,
      respectively) were completed. Average of the peak vertical and anterior/posterior
      AM acceleration (ACCvert and ACCbrake, respectively) and pGRFvert and pGRFbrake
      during the stance phase of gait were determined. Thirty randomly selected
      subjects served as the training dataset to develop generalized equations to
      predict pGRFvert and pGRFbrake. Using a holdout approach, the remaining 9
      subjects were used to test the accuracy of the models. Generalized equations to
      predict pGRFvert and pGRFbrake included ACCvert and ACCbrake, respectively, mass,
      type of locomotion (walk or run), and type of locomotion acceleration
      interaction. The average absolute percent differences between actual and
      predicted pGRFvert and pGRFbrake were 8.3% and 17.8%, respectively, when the
      models were applied to the test dataset. Repeated measures generalized regression
      equations were developed to predict pGRFvert and pGRFbrake from ActiGraph GT3X+
      AM acceleration for young adults walking and running. These equations provide a
      means to estimate GRFs without a force plate.

PMID- 24914947
TI  - Manipulating unconventional CH-based hydrogen bonding in a methyltransferase via
      noncanonical amino acid mutagenesis.
AB  - Recent studies have demonstrated that the active sites of S-adenosylmethionine
      (AdoMet)-dependent methyltransferases form strong carbon-oxygen (CH...O) hydrogen
      bonds with the substrate's sulfonium group that are important in AdoMet binding
      and catalysis. To probe these interactions, we substituted the noncanonical amino
      acid p-aminophenylalanine (pAF) for the active site tyrosine in the lysine
      methyltransferase SET7/9, which forms multiple CH...O hydrogen bonds to AdoMet
      and is invariant in SET domain enzymes. Using quantum chemistry calculations to
      predict the mutation's effects, coupled with biochemical and structural studies,
      we observed that pAF forms a strong CH...N hydrogen bond to AdoMet that is offset
      by an energetically unfavorable amine group rotamer within the SET7/9 active site
      that hinders AdoMet binding and activity. Together, these results illustrate that
      the invariant tyrosine in SET domain methyltransferases functions as an essential
      hydrogen bonding hub and cannot be readily substituted by residues bearing other
      hydrogen bond acceptors. 

PMID- 24914949
TI  - Magnetic exciton relaxation and spin-spin interaction by the time-delayed
      photoluminescence spectra of ZnO:Mn nanowires.
AB  - ZnO:Mn nanostructures are important diluted magnetic materials, but their
      electronic structure and magnetic origin are still not well understood. Here we
      studied the time-delayed and power-dependent photoluminescence spectra of Mn(II)
      doped ZnO nanowires with very low Mn concentration. From the time-delayed
      emission spectra, we obtained their electronic levels of single Mn ion
      replacement of Zn ions in ZnO nanowire. The high d-level emissions show up
      unusually because of the stronger p-d hybridization than that in ZnS, as well as
      the spin-spin coupling. After increasing Mn doping concentration, the
      ferromagentic cluster of the Mn-O-Mn with varied configurations can form and give
      individual emission peaks, which are in good agreement with the ab initio
      calculations. The presence of clustered Mn ions originates from their
      ferromagnetic coupling. The lifetimes of these d levels show strong excitation
      power-dependent behavior, indication of strong spin-dependent coherent emission.
      One-dimensional structure is critical for this coherent emission behavior. These
      results indicate that the d state is not within Mn ion only, but a localized
      exciton magnetic polaron, Mn-O-Mn coupling should be one source of ferromagnetism
      in ZnO:Mn lattice, the latter also can combine with free exciton for EMP and
      produce coherent EMP condensation and emission from a nanowire. This kind of
      nanowires can be expected to work for both spintronic and spin-photonic devices
      if we tune the transition metal ion doping concentration in it. 

PMID- 24914948
TI  - Generation and characterisation of a canine EGFP-HMGA2 prostate cancer in vitro
      model.
AB  - The architectural transcription factor HMGA2 is abundantly expressed during
      embryonic development. In several malignant neoplasias including prostate cancer,
      high re-expression of HMGA2 is correlated with malignancy and poor prognosis. The
      let-7 miRNA family is described to regulate HMGA2 negatively. The balance of let
      7 and HMGA2 is discussed to play a major role in tumour aetiology. To further
      analyse the role of HMGA2 in prostate cancer a stable and highly reproducible in
      vitro model system is precondition. Herein we established a canine CT1258-EGFP
      HMGA2 prostate cancer cell line stably overexpressing HMGA2 linked to EGFP and in
      addition the reference cell line CT1258-EGFP expressing solely EGFP to exclude
      EGFP-induced effects. Both recombinant cell lines were characterised by
      fluorescence microscopy, flow cytometry and immunocytochemistry. The
      proliferative effect of ectopically overexpressed HMGA2 was determined via BrdU
      assays. Comparative karyotyping of the derived and the initial CT1258 cell lines
      was performed to analyse chromosome consistency. The impact of the ectopic HMGA2
      expression on its regulator let-7a was analysed by quantitative real-time PCR.
      Fluorescence microscopy and immunocytochemistry detected successful expression of
      the EGFP-HMGA2 fusion protein exclusively accumulating in the nucleus. Gene
      expression analyses confirmed HMGA2 overexpression in CT1258-EGFP-HMGA2 in
      comparison to CT1258-EGFP and native cells. Significantly higher let-7a
      expression levels were found in CT1258-EGFP-HMGA2 and CT1258-EGFP. The BrdU
      assays detected an increased proliferation of CT1258-HMGA2-EGFP cells compared to
      CT1258-EGFP and native CT1258. The cytogenetic analyses of CT1258-EGFP and CT1258
      EGFP-HMGA2 resulted in a comparable hyperdiploid karyotype as described for
      native CT1258 cells. To further investigate the impact of recombinant
      overexpressed HMGA2 on CT1258 cells, other selected targets described to underlie
      HMGA2 regulation were screened in addition. The new fluorescent CT1258-EGFP-HMGA2
      cell line is a stable tool enabling in vitro and in vivo analyses of the HMGA2
      mediated effects on cells and the development and pathogenesis of prostate
      cancer. 

PMID- 24914951
TI  - The oldest gibbon fossil (Hylobatidae) from insular Southeast Asia: evidence from
      Trinil, (East Java, Indonesia), Lower/Middle Pleistocene.
AB  - A fossil femur excavated by Eugene Dubois between 1891-1900 in the Lower/Middle
      Pleistocene bonebed of the Trinil site (Java, Indonesia) was recognised by us as
      that of a Hylobatidae. The specimen, Trinil 5703 of the Dubois Collection
      (Leiden, The Netherlands), has the same distinctive form of fossilization that is
      seen in many of the bonebed fossils from Trinil in the collection. Anatomical
      comparison of Trinil 5703 to a sample of carnivore and primate femora, supported
      by morphometric analyses, lead to the attribution of the fossil to gibbon. Trinil
      5703 therefore provides the oldest insular record of this clade, one of the
      oldest known Hylobatidae fossils from Southeast Asia. Because living Hylobatidae
      only inhabit evergreen rain forests, the paleoenvironment within the river
      drainage in the greater Trinil area evidently included forests of this kind
      during the Lower/Middle Pleistocene as revealed here. 

PMID- 24914952
TI  - Rapid detection of DNMT3A R882 mutations in hematologic malignancies using a
      novel bead-based suspension assay with BNA(NC) probes.
AB  - Mutations in the human DNA methyl transferase 3A (DNMT3A) gene are recurrently
      identified in several hematologic malignancies such as Philadelphia chromosome
      negative myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS),
      MPN/MDS overlap syndromes and acute myeloid leukemia (AML). They have been shown
      to confer worse prognosis in some of these entities. Notably, about 2/3 of these
      mutations are missense mutations in codon R882 of the gene. We aimed at the
      development and validation of a novel easily applicable in routine practice
      method for quantitative detection of the DNMT3A p.R882C/H/R/S mutations bead
      based suspension assay. Initial testing on plasmid constructs showed excellent
      performance of BNA(NC)-modified probes with an optimal hybridization temperature
      of 66 degrees C. The method appeared to be quantitative and showed sensitivity of
      2.5% for different mutant alleles, making it significantly superior to direct
      sequencing. The assay was further validated on plasmid standards at different
      ratios between wild type and mutant alleles and on clinical samples from 120
      patients with known or suspected myeloid malignancies. This is the first report
      on the quantitative detection of DNMT3A R882 mutations using bead-based
      suspension assay with BNA(NC)-modified probes. Our data showed that it could be
      successfully implemented in the diagnostic work-up for patients with myeloid
      malignancies, as it is rapid, easy and reliable in terms of specificity and
      sensitivity. 

PMID- 24914954
TI  - Moving beyond the GM debate.
AB  - Once again, there are calls to reopen the debate on genetically modified (GM)
      crops. I find these calls frustrating and unnecessarily decisive. In my opinion
      the GM debate, on both sides, continues to hamper the urgent need to address the
      diverse and pressing challenges of global food security and environmental
      sustainability. The destructive power of the debate comes from its conflation of
      unrelated issues, coupled with deeply rooted misconceptions of the nature of
      agriculture.

PMID- 24914950
TI  - Targeting c-Met in melanoma: mechanism of resistance and efficacy of novel
      combinatorial inhibitor therapy.
AB  - Numerous tyrosine kinase inhibitors (TKIs) targeting c-Met are currently in
      clinical trials for several cancers. Their efficacy is limited due to the
      development of resistance. The present study aims to elucidate this mechanism of
      c-Met TKI resistance by investigating key mTOR and Wnt signaling proteins in
      melanoma cell lines resistant to SU11274, a c-Met TKI. Xenografts from RU
      melanoma cells treated with c-Met TKIs SU11274 and JNJ38877605 showed a 7- and 6
      fold reduction in tumor size, respectively. Resistant cells displayed
      upregulation of phosphorylated c-Met, mTOR, p70S6Kinase, 4E-BP1, ERK, LRP6, and
      active beta-catenin. In addition, GATA-6, a Wnt signaling regulator, was
      upregulated, and Axin, a negative regulator of the Wnt pathway, was downregulated
      in resistant cells. Modulation of these mTOR and Wnt pathway proteins was also
      prevented by combination treatment with SU11274, everolimus, an mTOR inhibitor,
      and XAV939, a Wnt inhibitor. Treatment with everolimus, resulted in 56% growth
      inhibition, and a triple combination of SU11274, everolimus and XAV939, resulted
      in 95% growth inhibition in RU cells. The V600E BRAF mutation was found to be
      positive only in MU cells. Combination treatment with a c-Met TKI and a BRAF
      inhibitor displayed a synergistic effect in reducing MU cell viability. These
      studies indicate activation of mTOR and Wnt signaling pathways in c-Met TKI
      resistant melanoma cells and suggest that concurrent targeting of c-Met, mTOR,
      and Wnt pathways and BRAF may improve efficacy over traditional TKI monotherapy
      in melanoma patients. 

PMID- 24914953
TI  - Modulation of cortical activity by transcranial direct current stimulation in
      patients with affective disorder.
AB  - Transcranial direct current stimulation (tDCS) has been shown to have
      antidepressant efficacy in patients experiencing a major depressive episode, but
      little is known about the underlying neurophysiology. The purpose of our study
      was to investigate the acute effects of tDCS on cortical activity using
      electroencephalography (EEG) in patients with an affective disorder. Eighteen
      patients diagnosed with an affective disorder and experiencing a depressive
      episode participated in a sham-controlled study of tDCS, each receiving a session
      of active (2 mA for 20 minutes) and sham tDCS to the left dorsolateral prefrontal
      cortex (DLPFC). The effects of tDCS on EEG activity were assessed after each
      session using event-related potentials (ERP) and measurement of spectral activity
      during a visual working memory (VWM) task. We observed task and intervention
      dependent effects on both ERPs and task-related alpha and theta activity, where
      active compared to sham stimulation resulted in a significant reduction in the N2
      amplitude and reduced theta activity over frontal areas during memory retrieval.
      In summary a single session of anodal tDCS stimulation to the left DLPFC during a
      major depressive episode resulted in modulated brain activity evident in task
      related EEG. Effects on the N2 and frontal theta activity likely reflect
      modulated activity in the medial frontal cortex and hence indicate that the after
      effects of tDCS extend beyond the direct focal effects to the left DLPFC. 

PMID- 24914955
TI  - SNX31: a novel sorting nexin associated with the uroplakin-degrading
      multivesicular bodies in terminally differentiated urothelial cells.
AB  - Uroplakins (UP), a group of integral membrane proteins, are major urothelial
      differentiation products that form 2D crystals of 16-nm particles (urothelial
      plaques) covering the apical surface of mammalian bladder urothelium. They
      contribute to the urothelial barrier function and, one of them, UPIa, serves as
      the receptor for uropathogenic Escherichia coli. It is therefore important to
      understand the mechanism by which these surface-associated uroplakins are
      degraded. While it is known that endocytosed uroplakin plaques are targeted to
      and line the multivesicular bodies (MVBs), it is unclear how these rigid-looking
      plaques can go to the highly curved membranes of intraluminal vesicles (ILVs).
      From a cDNA subtraction library, we identified a highly urothelium-specific
      sorting nexin, SNX31. SNX31 is expressed, like uroplakins, in terminally
      differentiated urothelial umbrella cells where it is predominantly associated
      with MVBs. Apical membrane proteins including uroplakins that are surface biotin
      tagged are endocytosed and targeted to the SNX31-positive MVBs. EM localization
      demonstrated that SNX31 and uroplakins are both associated not only with the
      limiting membranes of MVBs containing uroplakin plaques, but also with ILVs.
      SNX31 can bind, on one hand, the PtdIns3P-enriched lipids via its N-terminal PX
      domain, and, on the other hand, it binds uroplakins as demonstrated by co
      immunoprecipitation and proximity ligation assay, and by its reduced membrane
      association in uroplakin II-deficient urothelium. The fact that in urothelial
      umbrella cells MVBs are the only major intracellular organelles enriched in both
      PtdIns3P and uroplakins may explain SNX31's MVB-specificity in these cells.
      However, in MDCK and other cultured cells transfected SNX31 can bind to early
      endosomes possibly via lipids. These data support a model in which SNX31 mediates
      the endocytic degradation of uroplakins by disassembling/collapsing the MVB
      associated uroplakin plaques, thus enabling the uroplakin-containing (but
      'softened') membranes to bud and form the ILVs for lysosomal degradation and/or
      exosome formation. 

PMID- 24914956
TI  - Source-identifying biomarker ions between environmental and clinical Burkholderia
      pseudomallei using whole-cell matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS).
AB  - Burkholderia pseudomallei is the causative agent of melioidosis, which is an
      endemic disease in Northeast Thailand and Northern Australia. Environmental
      reservoirs, including wet soils and muddy water, serve as the major sources for
      contributing bacterial infection to both humans and animals. The whole-cell
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (whole-cell MALDI-TOF MS) has recently been applied as a rapid, accurate, and
      high-throughput tool for clinical diagnosis and microbiological research. In this
      present study, we employed a whole-cell MALDI-TOF MS approach for assessing its
      potency in clustering a total of 11 different B. pseudomallei isolates
      (consisting of 5 environmental and 6 clinical isolates) with respect to their
      origins and to further investigate the source-identifying biomarker ions
      belonging to each bacterial group. The cluster analysis demonstrated that six out
      of eleven isolates were grouped correctly to their sources. Our results revealed
      a total of ten source-identifying biomarker ions, which exhibited statistically
      significant differences in peak intensity between average environmental and
      clinical mass spectra using ClinProTools software. Six out of ten mass ions were
      assigned as environmental-identifying biomarker ions (EIBIs), including, m/z
      4,056, 4,214, 5,814, 7,545, 7,895, and 8,112, whereas the remaining four mass
      ions were defined as clinical-identifying biomarker ions (CIBIs) consisting of
      m/z 3,658, 6,322, 7,035, and 7,984. Hence, our findings represented, for the
      first time, the source-specific biomarkers of environmental and clinical B.
      pseudomallei. 

PMID- 24914957
TI  - Does occupational exposure to solvents and pesticides in association with
      glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of
      bladder cancer? The Belgrade case-control study.
AB  - OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1
      and T1 gene polymorphisms and potential effect modification by occupational
      exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS
      AND METHODS: A hospital-based case-control study of bladder cancer in men
      comprised 143 histologically confirmed cases and 114 age-matched male controls.
      Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by
      polymerase chain reaction method. Single nucleotide polymorphism of glutathione S
      transferase A1 and P1 was identified by restriction fragment length polymorphism
      method. As a measure of effect size, odds ratio (OR) with corresponding 95%
      confidence interval (95%CI) was calculated. RESULTS: The glutathione S
      transferase A1, T1 and P1 genotypes did not contribute independently toward the
      risk of bladder cancer, while the glutathione S-transferase M1-null genotype was
      overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032). The most
      pronounced effect regarding occupational exposure to solvents and glutathione S
      transferase genotype on bladder cancer risk was observed for the low activity
      glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001).
      The glutathione S-transferase M1-null genotype also enhanced the risk of bladder
      cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p =
      0.001). The risk of bladder cancer development was 5.3-fold elevated among
      glutathione S-transferase T1-active patients exposed to solvents in comparison
      with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p
      = 0.002). Moreover, men with glutathione S-transferase T1-active genotype exposed
      to pesticides exhibited 4.5 times higher risk in comparison with unexposed
      glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067).
      CONCLUSION: Null or low-activity genotypes of the glutathione S-transferase A1,
      T1, and P1 did not contribute independently towards the risk of bladder cancer in
      males. However, in association with occupational exposure, low activity
      glutathione S-transferase A1 and glutathione S-transferase M1-null as well as
      glutathione S-transferase T1-active genotypes increase individual susceptibility
      to bladder cancer.

PMID- 24914959
TI  - Entropy and gravity concepts as new methodological indexes to investigate
      technological convergence: patent network-based approach.
AB  - The volatility and uncertainty in the process of technological developments are
      growing faster than ever due to rapid technological innovations. Such phenomena
      result in integration among disparate technology fields. At this point, it is a
      critical research issue to understand the different roles and the propensity of
      each element technology for technological convergence. In particular, the network
      based approach provides a holistic view in terms of technological linkage
      structures. Furthermore, the development of new indicators based on network
      visualization can reveal the dynamic patterns among disparate technologies in the
      process of technological convergence and provide insights for future
      technological developments. This research attempts to analyze and discover the
      patterns of the international patent classification codes of the United States
      Patent and Trademark Office's patent data in printed electronics, which is a
      representative technology in the technological convergence process. To this end,
      we apply the physical idea as a new methodological approach to interpret
      technological convergence. More specifically, the concepts of entropy and gravity
      are applied to measure the activities among patent citations and the binding
      forces among heterogeneous technologies during technological convergence. By
      applying the entropy and gravity indexes, we could distinguish the characteristic
      role of each technology in printed electronics. At the technological convergence
      stage, each technology exhibits idiosyncratic dynamics which tend to decrease
      technological differences and heterogeneity. Furthermore, through nonlinear
      regression analysis, we have found the decreasing patterns of disparity over a
      given total period in the evolution of technological convergence. This research
      has discovered the specific role of each element technology field and has
      consequently identified the co-evolutionary patterns of technological
      convergence. These new findings on the evolutionary patterns of technological
      convergence provide some implications for engineering and technology foresight
      research, as well as for corporate strategy and technology policy. 

PMID- 24914958
TI  - Species divergence and phylogenetic variation of ecophysiological traits in
      lianas and trees.
AB  - The climbing habit is an evolutionary key innovation in plants because it is
      associated with enhanced clade diversification. We tested whether patterns of
      species divergence and variation of three ecophysiological traits that are
      fundamental for plant adaptation to light environments (maximum photosynthetic
      rate [A(max)], dark respiration rate [R(d)], and specific leaf area [SLA]) are
      consistent with this key innovation. Using data reported from four tropical
      forests and three temperate forests, we compared phylogenetic distance among
      species as well as the evolutionary rate, phylogenetic distance and phylogenetic
      signal of those traits in lianas and trees. Estimates of evolutionary rates
      showed that R(d) evolved faster in lianas, while SLA evolved faster in trees. The
      mean phylogenetic distance was 1.2 times greater among liana species than among
      tree species. Likewise, estimates of phylogenetic distance indicated that lianas
      were less related than by chance alone (phylogenetic evenness across 63 species),
      and trees were more related than expected by chance (phylogenetic clustering
      across 71 species). Lianas showed evenness for R(d), while trees showed
      phylogenetic clustering for this trait. In contrast, for SLA, lianas exhibited
      phylogenetic clustering and trees showed phylogenetic evenness. Lianas and trees
      showed patterns of ecophysiological trait variation among species that were
      independent of phylogenetic relatedness. We found support for the expected
      pattern of greater species divergence in lianas, but did not find consistent
      patterns regarding ecophysiological trait evolution and divergence. R(d) followed
      the species-level pattern, i.e., greater divergence/evolution in lianas compared
      to trees, while the opposite occurred for SLA and no pattern was detected for
      A(max). R(d) may have driven lianas' divergence across forest environments, and
      might contribute to diversification in climber clades.

PMID- 24914960
TI  - Quantum chemical cluster models for chemi- and physisorption of chlorobenzene on
      Si(111)-7*7.
AB  - Motivated by recent atomic manipulation experiments, we report quantum chemical
      calculations for chemi- and physisorption minima of chlorobenzene on the Si(111)
      7*7 surface. A density functional theory cluster approach is applied, using the
      B3LYP hybrid functional alongside Grimme's empirical dispersion corrections (D3).
      We were able to identify chemisorption sites of binding energies of 1.6 eV and
      physisorption energies of 0.6 eV, both in encouraging agreement with the trend of
      experimental data. The cluster approach opens up the possibility of a first
      principles based dynamical description of STM manipulation experiments on this
      system, the interpretation of which involves both the chemi- and physisorbed
      states. However, we found that special care has to be taken regarding the choice
      of clusters, basis sets, and the evaluation of the dispersion corrections. 

PMID- 24914961
TI  - Structure of the nisin leader peptidase NisP revealing a C-terminal autocleavage
      activity.
AB  - Nisin is a widely used antibacterial lantibiotic polypeptide produced by
      Lactococcus lactis. NisP belongs to the subtilase family and functions in the
      last step of nisin maturation as the leader-peptide peptidase. Deletion of the
      nisP gene in LAC71 results in the production of a non-active precursor peptide
      with the leader peptide unremoved. Here, the 1.1 A resolution crystal structure
      of NisP is reported. The structure shows similarity to other subtilases, which
      can bind varying numbers of Ca atoms. However, no calcium was found in this NisP
      structure, and the predicted calcium-chelating residues were placed so as to not
      allow NisP to bind a calcium ion in this conformation. Interestingly, a short
      peptide corresponding to its own 635-647 sequence was found to bind to the active
      site of NisP. Biochemical assays and native mass-spectrometric analysis confirmed
      that NisP possesses an auto-cleavage site between residues Arg647 and Ser648.
      Further, it was shown that NisP mutated at the auto-cleavage site (R647P/S648P)
      had full catalytic activity for nisin leader-peptide cleavage, although the C
      terminal region of NisP was no longer cleaved. Expressing this mutant in L.
      lactis LAC71 did not affect the production of nisin but did decrease the
      proliferation rate of the bacteria, suggesting the biological significance of the
      C-terminal auto-cleavage of NisP.

PMID- 24914962
TI  - A complement to the modern crystallographer's toolbox: caged gadolinium complexes
      with versatile binding modes.
AB  - A set of seven caged gadolinium complexes were used as vectors for introducing
      the chelated Gd(3+) ion into protein crystals in order to provide strong
      anomalous scattering for de novo phasing. The complexes contained multidentate
      ligand molecules with different functional groups to provide a panel of possible
      interactions with the protein. An exhaustive crystallographic analysis showed
      them to be nondisruptive to the diffraction quality of the prepared derivative
      crystals, and as many as 50% of the derivatives allowed the determination of
      accurate phases, leading to high-quality experimental electron-density maps. At
      least two successful derivatives were identified for all tested proteins.
      Structure refinement showed that the complexes bind to the protein surface or
      solvent-accessible cavities, involving hydrogen bonds, electrostatic and CH-pi
      interactions, explaining their versatile binding modes. Their high phasing power,
      complementary binding modes and ease of use make them highly suitable as a heavy
      atom screen for high-throughput de novo structure determination, in combination
      with the SAD method. They can also provide a reliable tool for the development of
      new methods such as serial femtosecond crystallography. 

PMID- 24914963
TI  - The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a
      novel redox switch that regulates its activities.
AB  - Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the
      dTMP synthesis cycle, is an antimalarial target because inhibition of its
      expression or function has been shown to be lethal to the parasite. As the wild
      type enzyme could not be crystallized, protein engineering of residues on the
      surface was carried out. The surface-engineered mutant PfSHMT-F292E was
      successfully crystallized and its structure was determined at 3 A resolution. The
      PfSHMT-F292E structure is a good representation of PfSHMT as this variant
      revealed biochemical properties similar to those of the wild type. Although the
      overall structure of PfSHMT is similar to those of other SHMTs, unique features
      including the presence of two loops and a distinctive cysteine pair formed by
      Cys125 and Cys364 in the tetrahydrofolate (THF) substrate binding pocket were
      identified. These structural characteristics have never been reported in other
      SHMTs. Biochemical characterization and mutation analysis of these two residues
      confirm that they act as a disulfide/sulfhydryl switch to regulate the THF
      dependent catalytic function of the enzyme. This redox switch is not present in
      the human enzyme, in which the cysteine pair is absent. The data reported here
      can be further exploited as a new strategy to specifically disrupt the activity
      of the parasite enzyme without interfering with the function of the human enzyme.

PMID- 24914964
TI  - The first structure of a bacterial diterpene cyclase: CotB2.
AB  - Sesquiterpenes and diterpenes are a diverse class of secondary metabolites that
      are predominantly derived from plants and some prokaryotes. The properties of
      these natural products encompass antitumor, antibiotic and even insecticidal
      activities. Therefore, they are interesting commercial targets for the chemical
      and pharmaceutical industries. Owing to their structural complexity, these
      compounds are more efficiently accessed by metabolic engineering of microbial
      systems than by chemical synthesis. This work presents the first crystal
      structure of a bacterial diterpene cyclase, CotB2 from the soil bacterium
      Streptomyces melanosporofaciens, at 1.64 A resolution. CotB2 is a diterpene
      cyclase that catalyzes the cyclization of the linear geranylgeranyl diphosphate
      to the tricyclic cyclooctat-9-en-7-ol. The subsequent oxidation of cyclooctat-9
      en-7-ol by two cytochrome P450 monooxygenases leads to bioactive cyclooctatin.
      Plasticity residues that decorate the active site of CotB2 have been mutated,
      resulting in alternative monocyclic, dicyclic and tricyclic compounds that show
      bioactivity. These new compounds shed new light on diterpene cyclase reaction
      mechanisms. Furthermore, the product of mutant CotB2(W288G) produced the new
      antibiotic compound (1R,3E,7E,11S,12S)-3,7,18-dolabellatriene, which acts
      specifically against multidrug-resistant Staphylococcus aureus. This opens a
      sustainable route for the industrial-scale production of this bioactive compound.

PMID- 24914965
TI  - CrowdPhase: crowdsourcing the phase problem.
AB  - The human mind innately excels at some complex tasks that are difficult to solve
      using computers alone. For complex problems amenable to parallelization,
      strategies can be developed to exploit human intelligence in a collective form:
      such approaches are sometimes referred to as 'crowdsourcing'. Here, a first
      attempt at a crowdsourced approach for low-resolution ab initio phasing in
      macromolecular crystallography is proposed. A collaborative online game named
      CrowdPhase was designed, which relies on a human-powered genetic algorithm, where
      players control the selection mechanism during the evolutionary process. The
      algorithm starts from a population of 'individuals', each with a random genetic
      makeup, in this case a map prepared from a random set of phases, and tries to
      cause the population to evolve towards individuals with better phases based on
      Darwinian survival of the fittest. Players apply their pattern-recognition
      capabilities to evaluate the electron-density maps generated from these sets of
      phases and to select the fittest individuals. A user-friendly interface, a
      training stage and a competitive scoring system foster a network of well trained
      players who can guide the genetic algorithm towards better solutions from
      generation to generation via gameplay. CrowdPhase was applied to two synthetic
      low-resolution phasing puzzles and it was shown that players could successfully
      obtain phase sets in the 30 degrees  phase error range and corresponding
      molecular envelopes showing agreement with the low-resolution models. The
      successful preliminary studies suggest that with further development the
      crowdsourcing approach could fill a gap in current crystallographic methods by
      making it possible to extract meaningful information in cases where limited
      resolution might otherwise prevent initial phasing. 

PMID- 24914966
TI  - Structure and mechanism of a nonhaem-iron SAM-dependent C-methyltransferase and
      its engineering to a hydratase and an O-methyltransferase.
AB  - In biological systems, methylation is most commonly performed by
      methyltransferases (MTs) using the electrophilic methyl source S-adenosyl-L
      methionine (SAM) via the S(N)2 mechanism. (2S,3S)-beta-Methylphenylalanine, a
      nonproteinogenic amino acid, is a building unit of the glycopeptide antibiotic
      mannopeptimycin. The gene product of mppJ from the mannopeptimycin-biosynthetic
      gene cluster is the MT that methylates the benzylic C atom of phenylpyruvate
      (Ppy) to give betaMePpy. Although the benzylic C atom of Ppy is acidic, how its
      nucleophilicity is further enhanced to become an acceptor for C-methylation has
      not conclusively been determined. Here, a structural approach is used to address
      the mechanism of MppJ and to engineer it for new functions. The purified MppJ
      displays a turquoise colour, implying the presence of a metal ion. The crystal
      structures reveal MppJ to be the first ferric ion SAM-dependent MT. An additional
      four structures of binary and ternary complexes illustrate the molecular
      mechanism for the metal ion-dependent methyltransfer reaction. Overall, MppJ has
      a nonhaem iron centre that bind, orients and activates the alpha-ketoacid
      substrate and has developed a sandwiched bi-water device to avoid the formation
      of the unwanted reactive oxo-iron(IV) species during the C-methylation reaction.
      This discovery further prompted the conversion of the MT into a
      structurally/functionally unrelated new enzyme. Through stepwise mutagenesis and
      manipulation of coordination chemistry, MppJ was engineered to perform both Lewis
      acid-assisted hydration and/or O-methyltransfer reactions to give stereospecific
      new compounds. This process was validated by six crystal structures. The results
      reported in this study will facilitate the development and design of new
      biocatalysts for difficult-to-synthesize biochemicals.

PMID- 24914967
TI  - Structure of the phosphotransferase domain of the bifunctional aminoglycoside
      resistance enzyme AAC(6')-Ie-APH(2'')-Ia.
AB  - The bifunctional acetyltransferase(6')-Ie-phosphotransferase(2'')-Ia [AAC(6')-Ie
      APH(2'')-Ia] is the most important aminoglycoside-resistance enzyme in Gram
      positive bacteria, conferring resistance to almost all known aminoglycoside
      antibiotics in clinical use. Owing to its importance, this enzyme has been the
      focus of intensive research since its isolation in the mid-1980s but, despite
      much effort, structural details of AAC(6')-Ie-APH(2'')-Ia have remained elusive.
      The structure of the Mg2GDP complex of the APH(2'')-Ia domain of the bifunctional
      enzyme has now been determined at 2.3 A resolution. The structure of APH(2'')-Ia
      is reminiscent of the structures of other aminoglycoside phosphotransferases,
      having a two-domain architecture with the nucleotide-binding site located at the
      junction of the two domains. Unlike the previously characterized APH(2'')-IIa and
      APH(2'')-IVa enzymes, which are capable of utilizing both ATP and GTP as the
      phosphate donors, APH(2'')-Ia uses GTP exclusively in the phosphorylation of the
      aminoglycoside antibiotics, and in this regard closely resembles the GTP
      dependent APH(2'')-IIIa enzyme. In APH(2'')-Ia this GTP selectivity is governed
      by the presence of a 'gatekeeper' residue, Tyr100, the side chain of which
      projects into the active site and effectively blocks access to the adenine
      binding template. Mutation of this tyrosine residue to a less bulky phenylalanine
      provides better access for ATP to the NTP-binding template and converts APH(2'')
      Ia into a dual-specificity enzyme. 

PMID- 24914969
TI  - Ten years of probabilistic estimates of biocrystal solvent content: new insights
      via nonparametric kernel density estimate.
AB  - The probabilistic estimate of the solvent content (Matthews probability) was
      first introduced in 2003. Given that the Matthews probability is based on prior
      information, revisiting the empirical foundation of this widely used solvent
      content estimate is appropriate. The parameter set for the original Matthews
      probability distribution function employed in MATTPROB has been updated after ten
      years of rapid PDB growth. A new nonparametric kernel density estimator has been
      implemented to calculate the Matthews probabilities directly from empirical
      solvent-content data, thus avoiding the need to revise the multiple parameters of
      the original binned empirical fit function. The influence and dependency of other
      possible parameters determining the solvent content of protein crystals have been
      examined. Detailed analysis showed that resolution is the primary and dominating
      model parameter correlated with solvent content. Modifications of protein
      specific density for low molecular weight have no practical effect, and there is
      no correlation with oligomerization state. A weak, and in practice irrelevant,
      dependency on symmetry and molecular weight is present, but cannot be
      satisfactorily explained by simple linear or categorical models. The Bayesian
      argument that the observed resolution represents only a lower limit for the true
      diffraction potential of the crystal is maintained. The new kernel density
      estimator is implemented as the primary option in the MATTPROB web application at
      http://www.ruppweb.org/mattprob/. 

PMID- 24914968
TI  - A point mutation in the [2Fe-2S] cluster binding region of the NAF-1 protein
      (H114C) dramatically hinders the cluster donor properties.
AB  - NAF-1 is an important [2Fe-2S] NEET protein associated with human health and
      disease. A mis-splicing mutation in NAF-1 results in Wolfram Syndrome type 2, a
      lethal childhood disease. Upregulation of NAF-1 is found in epithelial breast
      cancer cells, and suppression of NAF-1 expression by knockdown significantly
      suppresses tumor growth. Key to NAF-1 function is the NEET fold with its [2Fe-2S]
      cluster. In this work, the high-resolution structure of native NAF-1 was
      determined to 1.65 A resolution (R factor = 13.5%) together with that of a mutant
      in which the single His ligand of its [2Fe-2S] cluster, His114, was replaced by
      Cys. The NAF-1 H114C mutant structure was determined to 1.58 A resolution (R
      factor = 16.0%). All structural differences were localized to the cluster binding
      site. Compared with native NAF-1, the [2Fe-2S] clusters of the H114C mutant were
      found to (i) be 25-fold more stable, (ii) have a redox potential that is 300 mV
      more negative and (iii) have their cluster donation/transfer function abolished.
      Because no global structural differences were found between the mutant and the
      native (wild-type) NAF-1 proteins, yet significant functional differences exist
      between them, the NAF-1 H114C mutant is an excellent tool to decipher the
      underlying biological importance of the [2Fe-2S] cluster of NAF-1 in vivo. 

PMID- 24914970
TI  - Coiled-coil deformations in crystal structures: the measles virus phosphoprotein
      multimerization domain as an illustrative example.
AB  - The structures of two constructs of the measles virus (MeV) phosphoprotein (P)
      multimerization domain (PMD) are reported and are compared with a third structure
      published recently by another group [Communie et al. (2013), J. Virol. 87, 7166
      7169]. Although the three structures all have a tetrameric and parallel coiled
      coil arrangement, structural comparison unveiled considerable differences in the
      quaternary structure and unveiled that the three structures suffer from
      significant structural deformation induced by intermolecular interactions within
      the crystal. These results show that crystal packing can bias conclusions about
      function and mechanism based on analysis of a single crystal structure, and they
      challenge to some extent the assumption according to which coiled-coil structures
      can be reliably predicted from the amino-acid sequence. Structural comparison
      also highlighted significant differences in the extent of disorder in the C
      terminal region of each monomer. The differential flexibility of the C-terminal
      region is also supported by size-exclusion chromatography and small-angle X-ray
      scattering studies, which showed that MeV PMD exists in solution as a dynamic
      equilibrium between two tetramers of different compaction. Finally, the possible
      functional implications of the flexibility of the C-terminal region of PMD are
      discussed. 

PMID- 24914971
TI  - Structural insights into the mechanism of calmodulin binding to death receptors.
AB  - The death receptors Fas, p75(NTR) and DR6 are key components of extrinsically
      activated apoptosis. Characterization of how they interact with the adaptors is
      crucial in order to unravel the signalling mechanisms. However, the exact
      conformation that their intracellular death domain adopts upon binding downstream
      partners remains unclear. One model suggests that it adopts a typical compact
      fold, whilst a second model proposed an open conformation. Calmodulin (CaM), a
      major calcium sensor, has previously been reported to be one of the Fas adaptors
      that modulate apoptosis. This work reports that CaM also binds directly to the
      death domains of p75(NTR) and DR6, indicating that it serves as a common
      modulator of the death receptors. Two crystal structures of CaM in complexes with
      the corresponding binding regions of Fas and p75(NTR) are also reported.
      Interestingly, the precise CaM-binding sites were mapped to different regions:
      helix 1 in Fas and helix 5 in p75(NTR) and DR6. A novel 1-11 motif for CaM
      binding was observed in p75(NTR). Modelling the complexes of CaM with full-length
      receptors reveals that the opening of the death domains would be essential in
      order to expose their binding sites for CaM. These results may facilitate
      understanding of the diverse functional repertoire of death receptors and CaM and
      provide further insights necessary for the design of potential therapeutic
      peptide agents. 

PMID- 24914972
TI  - In and out of the minor groove: interaction of an AT-rich DNA with the drug CD27.
AB  - The DNA of several pathogens is very rich in AT base pairs. Typical examples
      include the malaria parasite Plasmodium falciparum and the causative agents of
      trichomoniasis and trypanosomiases. This fact has prompted studies of drugs which
      interact with the minor groove of DNA, some of which are used in medical
      practice. Previous studies have been performed almost exclusively with the AATT
      sequence. New features should be uncovered through the study of different DNA
      sequences. In this paper, the crystal structure of the complex of the DNA duplex
      d(AAAATTTT)2 with the dicationic drug 4,4'-bis(imidazolinylamino)diphenylamine
      (CD27) is presented. The drug binds to the minor groove of DNA as expected, but
      it shows two new features that have not previously been described: (i) the drugs
      protrude from the DNA and interact with neighbouring molecules, so that they may
      act as cross-linking agents, and (ii) the drugs completely cover the whole minor
      groove of DNA and displace bound water. Thus, they may prevent the access to DNA
      of proteins such as AT-hook proteins. These features are also expected for other
      minor-groove binding drugs when associated with all-AT DNA. These findings allow
      a better understanding of this family of compounds and will help in the
      development of new, more effective drugs. New data on the biological interaction
      of CD27 with the causative agent of trichomoniasis, Trichomonas vaginalis, are
      also reported. 

PMID- 24914974
TI  - Structural basis for glucose tolerance in GH1 beta-glucosidases.
AB  - Product inhibition of beta-glucosidases (BGs) by glucose is considered to be a
      limiting step in enzymatic technologies for plant-biomass saccharification.
      Remarkably, some beta-glucosidases belonging to the GH1 family exhibit unusual
      properties, being tolerant to, or even stimulated by, high glucose
      concentrations. However, the structural basis for the glucose tolerance and
      stimulation of BGs is still elusive. To address this issue, the first crystal
      structure of a fungal beta-glucosidase stimulated by glucose was solved in native
      and glucose-complexed forms, revealing that the shape and electrostatic
      properties of the entrance to the active site, including the +2 subsite,
      determine glucose tolerance. The aromatic Trp168 and the aliphatic Leu173 are
      conserved in glucose-tolerant GH1 enzymes and contribute to relieving enzyme
      inhibition by imposing constraints at the +2 subsite that limit the access of
      glucose to the -1 subsite. The GH1 family beta-glucosidases are tenfold to 1000
      fold more glucose tolerant than GH3 BGs, and comparative structural analysis
      shows a clear correlation between active-site accessibility and glucose
      tolerance. The active site of GH1 BGs is located in a deep and narrow cavity,
      which is in contrast to the shallow pocket in the GH3 family BGs. These findings
      shed light on the molecular basis for glucose tolerance and indicate that GH1 BGs
      are more suitable than GH3 BGs for biotechnological applications involving plant
      cell-wall saccharification. 

PMID- 24914975
TI  - Engineering the internal cavity of neuroglobin demonstrates the role of the haem
      sliding mechanism.
AB  - Neuroglobin is a member of the globin family involved in neuroprotection; it is
      primarily expressed in the brain and retina of vertebrates. Neuroglobin belongs
      to the heterogeneous group of hexacoordinate globins that have evolved in
      animals, plants and bacteria, endowed with the capability of reversible
      intramolecular coordination, allowing the binding of small gaseous ligands (O2,
      NO and CO). In a unique fashion among haemoproteins, ligand-binding events in
      neuroglobin are dependent on the sliding of the haem itself within a preformed
      internal cavity, as revealed by the crystal structure of its CO-bound derivative.
      Point mutants of the neuroglobin internal cavity have been engineered and their
      functional and structural characterization shows that hindering the haem
      displacement leads to a decrease in CO affinity, whereas reducing the cavity
      volume without interfering with haem sliding has negligible functional effects. 

PMID- 24914973
TI  - Structural and functional analysis of the human spliceosomal DEAD-box helicase
      Prp28.
AB  - The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key
      role in the formation of an active spliceosome. Prp28 participates in the release
      of the U1 snRNP from the 5'-splice site during association of the U5.U4/U6 tri
      snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome
      to an activated spliceosome. Here, it is demonstrated that the purified helicase
      domain of human Prp28 (hPrp28DeltaN) binds ADP, whereas binding of ATP and ATPase
      activity could not be detected. ATP binding could not be observed for purified
      full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28
      gains ATP-binding activity. In order to understand the structural basis for the
      ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28DeltaN
      was determined at 2.0 A resolution. In the crystal the helicase domain adopts a
      wide-open conformation, as the two RecA-like domains are extraordinarily
      displaced from the productive ATPase conformation. Binding of ATP is hindered by
      a closed conformation of the P-loop, which occupies the space required for the
      gamma-phosphate of ATP. 

PMID- 24914976
TI  - Structure of tomato wound-induced leucine aminopeptidase sheds light on substrate
      specificity.
AB  - The acidic leucine aminopeptidase (LAP-A) from tomato is induced in response to
      wounding and insect feeding. Although LAP-A shows in vitro peptidase activity
      towards peptides and peptide analogs, it is not clear what kind of substrates LAP
      A hydrolyzes in vivo. In the current study, the crystal structure of LAP-A was
      determined to 2.20 A resolution. Like other LAPs in the M17 peptidase family, LAP
      A is a dimer of trimers containing six monomers of bilobal structure. Each
      monomer contains two metal ions bridged by a water or a hydroxyl ion at the
      active site. Modeling of different peptides or peptide analogs in the active site
      of LAP-A reveals a spacious substrate-binding channel that can bind peptides of
      five or fewer residues with few geometric restrictions. The sequence specificity
      of the bound peptide is likely to be selected by the structural and chemical
      restrictions on the amino acid at the P1 and P1' positions because these two
      amino acids have to bind perfectly at the active site for hydrolysis of the first
      peptide bond to occur. The hexameric assembly results in the merger of the open
      ends of the six substrate-binding channels from the LAP-A monomers to form a
      spacious central cavity allowing the hexameric LAP-A enzyme to simultaneously
      hydrolyze six peptides containing up to six amino acids each. The hexameric LAP-A
      enzyme may also hydrolyze long peptides or proteins if only one such substrate is
      bound to the hexamer because the substrate can extend through the central cavity
      and the two major solvent channels between the two LAP-A trimers. 

PMID- 24914977
TI  - Structural features underlying the selective cleavage of a novel exo-type maltose
      forming amylase from Pyrococcus sp. ST04.
AB  - A novel maltose-forming alpha-amylase (PSMA) was recently found in the
      hyperthermophilic archaeon Pyrococcus sp. ST04. This enzyme shows <13% amino-acid
      sequence identity to other known alpha-amylases and displays a unique enzymatic
      property in that it hydrolyzes both alpha-1,4-glucosidic and alpha-1,6-glucosidic
      linkages of substrates, recognizing only maltose units, in an exo-type manner.
      Here, the crystal structure of PSMA at a resolution of 1.8 A is reported, showing
      a tight ring-shaped tetramer with monomers composed of two domains: an N-domain
      (amino acids 1-341) with a typical GH57 family (beta/alpha)7-barrel fold and a C
      domain (amino acids 342-597) composed of alpha-helical bundles. A small closed
      cavity observed in proximity to the catalytic residues Glu153 and Asp253 at the
      domain interface has the appropriate volume and geometry to bind a maltose unit,
      accounting for the selective exo-type maltose hydrolysis of the enzyme. A narrow
      gate at the putative subsite +1 formed by residue Phe218 and Phe452 is essential
      for specific cleavage of glucosidic bonds. The closed cavity at the active site
      is connected to a short substrate-binding channel that extends to the central
      hole of the tetramer, exhibiting a geometry that is significantly different from
      classical maltogenic amylases or beta-amylases. The structural features of this
      novel exo-type maltose-forming alpha-amylase provide a molecular basis for its
      unique enzymatic characteristics and for its potential use in industrial
      applications and protein engineering. 

PMID- 24914978
TI  - O6-carboxymethylguanine in DNA forms a sequence context-dependent wobble base
      pair structure with thymine.
AB  - N-Nitrosation of glycine and its derivatives generates potent alkylating agents
      that can lead to the formation of O(6)-carboxymethylguanine (O(6)-CMG) in DNA.
      O(6)-CMG has been identified in DNA derived from human colon tissue and its
      occurrence has been linked to diets high in red and processed meats, implying an
      association with the induction of colorectal cancer. By analogy to O(6)
      methylguanine, O(6)-CMG is expected to be mutagenic, inducing G-to-A mutations
      that may be the molecular basis of increased cancer risk. Previously, the crystal
      structure of the DNA dodecamer d(CGCG[O(6)-CMG]ATTCGCG) has been reported, in
      which O(6)-CMG forms a Watson-Crick-type pair with thymine similar to the
      canonical A:T pair. In order to further investigate the versatility of O(6)-CMG
      in base-pair formation, the structure of the DNA dodecamer d(CGC[O(6)
      CMG]AATTTGCG) containing O(6)-CMG at a different position has been determined by
      X-ray crystallography using four crystal forms obtained under conditions
      containing different solvent ions (Sr(2+), Ba(2+), Mg(2+), K(+) or Na(+)) with
      and without Hoechst 33258. The most striking finding is that the pairing modes of
      O(6)-CMG with T are quite different from those previously reported. In the
      present dodecamer, the T bases are displaced (wobbled) into the major groove to
      form a hydrogen bond between the thymine N(3) N-H and the carboxyl group of O(6)
      CMG. In addition, a water molecule is bridged through two hydrogen bonds between
      the thymine O(2) atom and the 2-amino group of O(6)-CMG to stabilize the pairing.
      These interaction modes commonly occur in the four crystal forms, regardless of
      the differences in crystallization conditions. The previous and the present
      results show that O(6)-CMG can form a base pair with T in two alternative modes:
      the Watson-Crick type and a high-wobble type, the nature of which may depend on
      the DNA-sequence context. 

PMID- 24914980
TI  - L-allo-threonine aldolase with an H128Y/S292R mutation from Aeromonas jandaei DK
      39 reveals the structural basis of changes in substrate stereoselectivity.
AB  - L-allo-Threonine aldolase (LATA), a pyridoxal-5'-phosphate-dependent enzyme from
      Aeromonas jandaei DK-39, stereospecifically catalyzes the reversible
      interconversion of L-allo-threonine to glycine and acetaldehyde. Here, the
      crystal structures of LATA and its mutant LATA_H128Y/S292R were determined at
      2.59 and 2.50 A resolution, respectively. Their structures implied that
      conformational changes in the loop consisting of residues Ala123-Pro131, where
      His128 moved 4.2 A outwards from the active site on mutation to a tyrosine
      residue, regulate the substrate specificity for L-allo-threonine versus L
      threonine. Saturation mutagenesis of His128 led to diverse stereoselectivity
      towards L-allo-threonine and L-threonine. Moreover, the H128Y mutant showed the
      highest activity towards the two substrates, with an 8.4-fold increase towards L
      threonine and a 2.0-fold increase towards L-allo-threonine compared with the wild
      type enzyme. The crystal structures of LATA and its mutant LATA_H128Y/S292R
      reported here will provide further insights into the regulation of the
      stereoselectivity of threonine aldolases targeted for the catalysis of L-allo
      threonine/L-threonine synthesis. 

PMID- 24914979
TI  - Crystal structure of human CRMP-4: correction of intensities for lattice
      translocation disorder.
AB  - Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that
      are mainly involved in neuronal cell development. In humans, the CRMP family
      comprises five members. Here, crystal structures of human CRMP-4 in a truncated
      and a full-length version are presented. The latter was determined from two types
      of crystals, which were either twinned or partially disordered. The crystal
      disorder was coupled with translational NCS in ordered domains and manifested
      itself with a rather sophisticated modulation of intensities. The data were
      demodulated using either the two-lattice treatment of lattice-translocation
      effects or a novel method in which demodulation was achieved by independent
      scaling of several groups of intensities. This iterative protocol does not rely
      on any particular parameterization of the modulation coefficients, but uses the
      current refined structure as a reference. The best results in terms of R factors
      and map correlation coefficients were obtained using this new method. The
      determined structures of CRMP-4 are similar to those of other CRMPs. Structural
      comparison allowed the confirmation of known residues, as well as the
      identification of new residues, that are important for the homo- and hetero
      oligomerization of these proteins, which are critical to nerve-cell development.
      The structures provide further insight into the effects of medically relevant
      mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic
      activities of CRMPs. 

PMID- 24914981
TI  - Structural and functional characterization of human and murine C5a
      anaphylatoxins.
AB  - Complement is an ancient part of the innate immune system that plays a pivotal
      role in protection against invading pathogens and helps to clear apoptotic and
      necrotic cells. Upon complement activation, a cascade of proteolytic events
      generates the complement effectors, including the anaphylatoxins C3a and C5a.
      Signalling through their cognate G-protein coupled receptors, C3aR and C5aR,
      leads to a wide range of biological events promoting inflammation at the site of
      complement activation. The function of anaphylatoxins is regulated by circulating
      carboxypeptidases that remove their C-terminal arginine residue, yielding C3a
      desArg and C5a-desArg. Whereas human C3a and C3a-desArg adopt a canonical four
      helix bundle fold, the conformation of human C5a-desArg has recently been
      described as a three-helix bundle. Here, the crystal structures of an antagonist
      version of human C5a, A8(Delta71-73), and of murine C5a and C5a-desArg are
      reported. Whereas A8(Delta71-73) adopts a three-helix bundle conformation similar
      to human C5a-desArg, the two murine proteins form a four-helix bundle. A cell
      based functional assay reveals that murine C5a-desArg, in contrast to its human
      counterpart, exerts the same level of activition as murine C5a on its cognate
      receptor. The role of the different C5a conformations is discussed in relation to
      the differential activation of C5a receptors across species. 

PMID- 24914982
TI  - Structural and bioinformatic characterization of an Acinetobacter baumannii type
      II carrier protein.
AB  - Microorganisms produce a variety of natural products via secondary metabolic
      biosynthetic pathways. Two of these types of synthetic systems, the nonribosomal
      peptide synthetases (NRPSs) and polyketide synthases (PKSs), use large modular
      enzymes containing multiple catalytic domains in a single protein. These
      multidomain enzymes use an integrated carrier protein domain to transport the
      growing, covalently bound natural product to the neighboring catalytic domains
      for each step in the synthesis. Interestingly, some PKS and NRPS clusters contain
      free-standing domains that interact intermolecularly with other proteins. Being
      expressed outside the architecture of a multi-domain protein, these so-called
      type II proteins present challenges to understand the precise role they play.
      Additional structures of individual and multi-domain components of the NRPS
      enzymes will therefore provide a better understanding of the features that govern
      the domain interactions in these interesting enzyme systems. The high-resolution
      crystal structure of a free-standing carrier protein from Acinetobacter baumannii
      that belongs to a larger NRPS-containing operon, encoded by the ABBFA_003406
      ABBFA_003399 genes of A. baumannii strain AB307-0294, that has been implicated in
      A. baumannii motility, quorum sensing and biofilm formation, is presented here.
      Comparison with the closest structural homologs of other carrier proteins
      identifies the requirements for a conserved glycine residue and additional
      important sequence and structural requirements within the regions that interact
      with partner proteins. 

PMID- 24914983
TI  - Structures of inactive CRP species reveal the atomic details of the allosteric
      transition that discriminates cyclic nucleotide second messengers.
AB  - The prokaryotic global transcription factor CRP has been considered to be an
      ideal model for in-depth study of both the allostery of the protein and the
      differential utilization of the homologous cyclic nucleotide second messengers
      cAMP and cGMP. Here, atomic details from the crystal structures of two inactive
      CRP species, an apo form and a cGMP-bound form, in comparison with a known active
      conformation, the cAMP-CRP complex, provide macroscopic and microscopic insights
      into CRP allostery, which is coupled to specific discrimination between the two
      effectors. The cAMP-induced conformational transition, including dynamic
      fluctuations, can be driven by the fundamental folding forces that cause water
      soluble globular proteins to construct an optimized hydrophobic core, including
      secondary-structure formation. The observed conformational asymmetries underlie a
      negative cooperativity in the sequential binding of cyclic nucleotides and a
      stepwise manner of binding with discrimination between the effector molecules.
      Additionally, the finding that cGMP, which is specifically recognized in a syn
      conformation, induces an inhibitory conformational change, rather than a null
      effect, on CRP supports the intriguing possibility that cGMP signalling could be
      widely utilized in prokaryotes, including in aggressive inhibition of CRP-like
      proteins. 

PMID- 24914984
TI  - Structure solution of DNA-binding proteins and complexes with ARCIMBOLDO
      libraries.
AB  - Protein-DNA interactions play a major role in all aspects of genetic activity
      within an organism, such as transcription, packaging, rearrangement, replication
      and repair. The molecular detail of protein-DNA interactions can be best
      visualized through crystallography, and structures emphasizing insight into the
      principles of binding and base-sequence recognition are essential to
      understanding the subtleties of the underlying mechanisms. An increasing number
      of high-quality DNA-binding protein structure determinations have been witnessed
      despite the fact that the crystallographic particularities of nucleic acids tend
      to pose specific challenges to methods primarily developed for proteins.
      Crystallographic structure solution of protein-DNA complexes therefore remains a
      challenging area that is in need of optimized experimental and computational
      methods. The potential of the structure-solution program ARCIMBOLDO for the
      solution of protein-DNA complexes has therefore been assessed. The method is
      based on the combination of locating small, very accurate fragments using the
      program Phaser and density modification with the program SHELXE. Whereas for
      typical proteins main-chain alpha-helices provide the ideal, almost ubiquitous,
      small fragments to start searches, in the case of DNA complexes the binding
      motifs and DNA double helix constitute suitable search fragments. The aim of this
      work is to provide an effective library of search fragments as well as to
      determine the optimal ARCIMBOLDO strategy for the solution of this class of
      structures. 

PMID- 24914986
TI  - Structure of the LCMV nucleoprotein provides a template for understanding
      arenavirus replication and immunosuppression.
AB  - The X-ray crystal structure of the Lymphocytic choriomeningitis virus
      nucleoprotein C-terminal immunosuppressive domain (LCMV NPDelta340) was
      determined to 2.0 A resolution. The structure indicates that LCMV NPDelta340,
      like the other structurally characterized arenaviral nucleoproteins, adopts the
      fold of an exonuclease. This structure provides a crucial three-dimensional
      template for functional exploration of the replication and immunosuppression of
      this prototypic arenavirus. 

PMID- 24914985
TI  - Structural elucidation of the hormonal inhibition mechanism of the bile acid
      cholate on human carbonic anhydrase II.
AB  - The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that
      catalyze the reversible hydration/dehydration of CO2 into bicarbonate and a
      proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells
      of the gastric mucosa, where it serves an important role in cytoprotection
      through bicarbonate secretion. Physiological inhibition of HCA II via the bile
      acids contributes to mucosal injury in ulcerogenic conditions. This study details
      the weak biophysical interactions associated with the binding of a primary bile
      acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54
      A resolution revealed that cholate does not make any direct hydrogen-bond
      interactions with HCA II, but instead reconfigures the well ordered water network
      within the active site to promote indirect binding to the enzyme. Structural
      knowledge of the binding interactions of this nonsulfur-containing inhibitor with
      HCA II could provide the template design for high-affinity, isoform-specific
      therapeutic agents for a variety of diseases/pathological states, including
      cancer, glaucoma, epilepsy and osteoporosis. 

PMID- 24914987
TI  - Structure of the oligogalacturonate-specific KdgM porin.
AB  - The phytopathogenic Gram-negative bacterium Dickeya dadantii (Erwinia
      chrysanthemi) feeds on plant cell walls by secreting pectinases and utilizing the
      oligogalacturanate products. An outer membrane porin, KdgM, is indispensable for
      the uptake of these acidic oligosaccharides. Here, the crystal structure of KdgM
      determined to 1.9 A resolution is presented. KdgM is folded into a regular 12
      stranded antiparallel beta-barrel with a circular cross-section defining a
      transmembrane pore with a minimal radius of 3.1 A. Most of the loops that would
      face the cell exterior in vivo are disordered, but nevertheless mediate contact
      between densely packed membrane-like layers in the crystal. The channel is lined
      by two tracks of arginine residues facing each other across the pore, a feature
      that is conserved within the KdgM family and is likely to facilitate the
      diffusion of acidic oligosaccharides. 

PMID- 24914989
TI  - Non-covalent interactions at electrochemical interfaces: one model fits all?
AB  - The shift with increasing concentration of alkali-metal cations of the potentials
      of both the spike and the hump observed in the cyclic voltammograms of Pt(111)
      electrodes in sulfuric acid solutions is shown to obey the simple model recently
      developed by us to explain the effect of non-covalent interactions at the
      electrical double layer. The results suggest that the model, originally developed
      to describe the effect of alkali-metal cations on the cyclic voltammogram of
      cyanide-modified Pt(111) electrodes, is of general applicability and can explain
      quantitatively the effect of cations on the properties of the electrical double
      layer. 

PMID- 24914988
TI  - Structure of BamA, an essential factor in outer membrane protein biogenesis.
AB  - Outer membrane protein (OMP) biogenesis is an essential process for maintaining
      the bacterial cell envelope and involves the beta-barrel assembly machinery (BAM)
      for OMP recognition, folding and assembly. In Escherichia coli this function is
      orchestrated by five proteins: the integral outer membrane protein BamA of the
      Omp85 superfamily and four associated lipoproteins. To unravel the mechanism
      underlying OMP folding and insertion, the structure of the E. coli BamA beta
      barrel and P5 domain was determined at 3 A resolution. These data add information
      beyond that provided in the recently published crystal structures of BamA from
      Haemophilus ducreyi and Neisseria gonorrhoeae and are a valuable basis for the
      interpretation of pertinent functional studies. In an 'open' conformation, E.
      coli BamA displays a significant degree of flexibility between P5 and the barrel
      domain, which is indicative of a multi-state function in substrate transfer. E.
      coli BamA is characterized by a discontinuous beta-barrel with impaired beta1
      beta16 strand interactions denoted by only two connecting hydrogen bonds and a
      disordered C-terminus. The 16-stranded barrel surrounds a large cavity which
      implies a function in OMP substrate binding and partial folding. These findings
      strongly support a mechanism of OMP biogenesis in which substrates are partially
      folded inside the barrel cavity and are subsequently released laterally into the
      lipid bilayer. 

PMID- 24914990
TI  - Development of a suspension array assay in multiplex for the simultaneous
      measurement of serum levels of four eosinophil granule proteins.
AB  - The concentrations of major basic protein (MBP), eosinophil cationic protein
      (ECP), eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO) have
      been associated with eosinophilic disease severity. Whereas a variety of
      techniques have been used to measure individual eosinophil granule protein
      concentration, none of these methods efficiently measures MBP, ECP, EDN and EPO
      simultaneously. A multiplex suspension array system was developed to
      simultaneously measure the concentrations of MBP, ECP, EDN and EPO in serum. The
      assay showed excellent inter- and intra-assay reliability, and serum levels of
      MBP, ECP and EDN from eosinophilic subjects analyzed by ELISA and multiplex were
      highly correlated (r=0.8579; P<0.0001, r=0.6356; P=0.0006 and r=0.8600; P<0.0001,
      respectively, Spearman rank correlation). Moreover, the multiplex assay required
      500-fold less serum than a single ELISA to achieve comparable sensitivity.
      Absolute eosinophil count and eosinophil surface expression of the activation
      marker, CD69, were significantly correlated with concentrations of MBP, EDN and
      EPO, but not ECP, in serum from eosinophilic subjects. Furthermore, subjects with
      eosinophilic gastrointestinal disorder and normal peripheral absolute eosinophil
      counts (<0.5*10(9)/l) had significantly increased concentrations of MBP
      (P<0.0001), ECP (P<0.0001), EDN (P=0.0001) and EPO (P<0.0001) compared to normal
      donors. In summary, the eosinophil granule protein multiplex assay provides a
      rapid and reliable way to measure eosinophil granule protein levels and should
      prove useful in assessing patterns of degranulation in patients with eosinophilic
      disorders. 

PMID- 24914991
TI  - Proteome profiling of virus-host interactions of wild type and attenuated measles
      virus strains.
AB  - Quantitative gel-based proteomics (2D DIGE coupled to MALDI-TOF/TOF MS) has been
      used to investigate the effects of different measles virus (MV) strains on the
      host cell proteome. A549/hSLAM cells were infected either with wild type MV
      strains, an attenuated vaccine or a multiple passaged Vero cell adapted strain.
      By including interferon beta treatment as a control it was possible to
      distinguish between the classical antiviral response and changes induced
      specifically by the different strains. Of 38 differentially expressed proteins in
      total (p-value <=0.05, fold change >=2), 18 proteins were uniquely modulated
      following MV infection with up to 9 proteins specific per individual strain.
      Interestingly, wt strains displayed distinct protein patterns particularly during
      the late phase of infection. Proteins were grouped into cytoskeleton, metabolism,
      transcription/translation, immune response and mitochondrial proteins.
      Bioinformatics analysis revealed mostly changes in proteins regulating cell death
      and apoptosis. Surprisingly, wt strains affected the cytokeratin system much
      stronger than the vaccine strain. To our knowledge, this is the first study on
      the MV-host proteome addressing interstrain differences. BIOLOGICAL SIGNIFICANCE:
      In the present study we investigated the host cell proteome upon measles virus
      (MV) infection. The novelty about this study is the side-by side comparison of
      different strains from the same virus, which has not been done at the proteome
      level for any other virus including MV. We used different virus strains including
      a vaccine strain, wild type isolates derived from MV-infected patients as well as
      a Vero cell adapted strain, which serves as an intermediate between vaccine and
      wild type strain. We observed differences between vaccine and wild type strains
      as well as common features between different wild type strains. Perhaps one of
      the most surprising findings was that differences did not only occur between wild
      type and vaccine or Vero cell adapted strains but also between different wild
      type strains. In fact our study suggests that besides the cytokeratin and the IFN
      system wild type viruses seem to differ as much among each other than from
      vaccine strains. Thus our results are suggestive of complex and diverse virus
      host interactions which differ considerably between different wild type strains.
      Our data indicate that interstrain differences are prominent and have so far been
      neglected by proteomics studies.

PMID- 24914992
TI  - Assessment of the europium(III) binding sites on albumin using fluorescence
      spectroscopy.
AB  - Intrinsic fluorescence quenching of bovine serum albumin (BSA) and europium(III)
      luminescence in BSA complexes were investigated. The number of BSA binding sites
      (n) and equilibrium constant (Keq) values were determined from both measurements
      provided qualitatively different results. While the modified Stern-Volmer
      relation for BSA fluorescence quenching gave n = 1 at pH 4.5 and pH 6, two sets
      of binding sites were determined from Eu(3+) luminescence with n1 = 2, n2 = 4 at
      pH 6 and n1 = 1, n2 = 2 at pH 4.5. The model explaining the discrepancy between
      the results obtained by these fluorescent approaches was suggested, and the
      limitations in application of the "log-log" Stern-Volmer plots in analysis of
      binding processes were discussed. 

PMID- 24914993
TI  - Synthesis, structural analysis, theoretical studies of some lawsone derivatives.
AB  - A series of lawsone derivatives are synthesized. The structures of the
      synthesized compounds are analyzed by FT-IR, Mass, Elemental analysis, (1)H,
      (13)C, HSQC, HMBC and theoretical studies. 

PMID- 24914994
TI  - New fluorescent symmetrically substituted perylene-3,4,9,10-dianhydride-azohybrid
      dyes: synthesis and spectroscopic studies.
AB  - Five phenolic azo-dyes (3a-e) were synthesized by diazo coupling of the suitably
      substituted anilines (1a-e) with phenol at low temperature in alkaline medium.
      The resulting dyes have low solubility in aqueous medium due to lack of
      carboxylic or sulfonic solubilizing functionalities. The hybridization of
      perylene dianhydride with phenolic azo-dyes was achieved by the nucleophilic
      aromatic substitution (SNAr) reaction of perylene-3,4,9,10-dianhydride 4 with
      phenolic azo-dyes 3a-e in basic medium. The hybrid dyes exhibit absorption maxima
      lambdamax in the range 440-460nm in aqueous medium due to presence of azo linkage
      and highly conjugated system of pi bonds. Fluorescence spectra of these dyes in
      water show sharp emission peaks with small band widths. The structures of
      perylene-azo dyes were confirmed by FTIR and NMR spectroscopy. 

PMID- 24914996
TI  - Membrane interactions of fusogenic coiled-coil peptides: implications for
      lipopeptide mediated vesicle fusion.
AB  - Fusion of lipid membranes is an important natural process for the intra- and
      intercellular exchange of molecules. However, little is known about the actual
      fusion mechanism at the molecular level. In this study we examine a system that
      models the key features of this process. For the molecular recognition between
      opposing membranes two membrane anchored heterodimer coiled-coil forming peptides
      called 'E' (EIAALEK)3 and 'K' (KIAALKE)3 were used. Lipid monolayers and IR
      reflection absorption spectroscopy (IRRAS) revealed the interactions of the
      peptides 'E', 'K', and their parallel coiled-coil complex 'E/K' with the
      phospholipid membranes and thereby mimicked the pre- and postfusion states,
      respectively. The peptides adopted alpha-helical structures and were incorporated
      into the monolayers with parallel orientation. The strength of binding to the
      monolayer differed for the peptides and tethering them to the membrane increased
      the interactions even further. Remarkably, these interactions played a role even
      in the postfusion state. These findings shed light on important mechanistic
      details of the membrane fusion process in this model system. Furthermore, their
      implications will help to improve the rational design of new artificial membrane
      fusion systems, which have a wide range of potential applications in
      supramolecular chemistry and biomedicine. 

PMID- 24914995
TI  - Influence of elastin-like polypeptide and hydrophobin on recombinant
      hemagglutinin accumulations in transgenic tobacco plants.
AB  - Fusion protein strategies are useful tools to enhance expression and to support
      the development of purification technologies. The capacity of fusion protein
      strategies to enhance expression was explored in tobacco leaves and seeds. C
      terminal fusion of elastin-like polypeptides (ELP) to influenza hemagglutinin
      under the control of either the constitutive CaMV 35S or the seed-specific USP
      promoter resulted in increased accumulation in both leaves and seeds compared to
      the unfused hemagglutinin. The addition of a hydrophobin to the C-terminal end of
      hemagglutinin did not significantly increase the expression level. We show here
      that, depending on the target protein, both hydrophobin fusion and ELPylation
      combined with endoplasmic reticulum (ER) targeting induced protein bodies in
      leaves as well as in seeds. The N-glycosylation pattern indicated that KDEL
      sequence-mediated retention of leaf-derived hemagglutinins and hemagglutinin
      hydrophobin fusions were not completely retained in the ER. In contrast,
      hemagglutinin-ELP from leaves contained only the oligomannose form, suggesting
      complete ER retention. In seeds, ER retention seems to be nearly complete for all
      three constructs. An easy and scalable purification method for ELPylated proteins
      using membrane-based inverse transition cycling could be applied to both leaf-
      and seed-expressed hemagglutinins. 

PMID- 24914997
TI  - Biocatalytic and antimicrobial activities of gold nanoparticles synthesized by
      Trichoderma sp.
AB  - The aim of this work was to synthesize gold nanoparticles by Trichoderma viride
      and Hypocrea lixii. The biosynthesis of the nanoparticles was very rapid and took
      10 min at 30  degrees C when cell-free extract of the T. viride was used, which
      was similar by H. lixii but at 100  degrees C. Biomolecules present in cell free
      extracts of both fungi were capable to synthesize and stabilize the formed
      particles. Synthesis procedure was very quick and environment friendly which did
      not require subsequent processing. The biosynthesized nanoparticles served as an
      efficient biocatalyst which reduced 4-nitrophenol to 4-aminophenol in the
      presence of NaBH4 and had antimicrobial activity against pathogenic bacteria. To
      the best of our knowledge, this is the first report of such rapid biosynthesis of
      gold nanoparticles within 10 min by Trichoderma having plant growth promoting and
      plant pathogen control abilities, which served both, as an efficient biocatalyst,
      and a potent antimicrobial agent.

PMID- 24914998
TI  - Thermochemical and trace element behavior of coal gangue, agricultural biomass
      and their blends during co-combustion.
AB  - The thermal decomposition behavior of coal gangue, peanut shell, wheat straw and
      their blends during combustion were determined via thermogravimetric analysis.
      The coal gangue/agricultural biomass blends were prepared in four weight ratios
      and oxidized under dynamic conditions from room temperature to 1000  degrees C by
      various heating rates. Kinetic models were carried out to evaluate the thermal
      reactivity. The overall mass balance was performed to assess the partition
      behavior of coal gangue, peanut shell and their blends during combustion in a
      fixed bed reactor. The decomposition processes of agricultural biomass included
      evaporation, release of volatile matter and combustion as well as char oxidation.
      The thermal reactivity of coal gangue could be improved through the addition of
      agricultural biomass in suitable proportion and subsequent appropriate heating
      rate during combustion. In combination with the heating value and base/acid ratio
      limitations, a blending ratio of 30% agricultural biomass is conservatively
      selected as optimum blending.

PMID- 24914999
TI  - Closure of Fontan fenestration with the use of covered stents: short- and mid
      term results in a cohort of 50 patients.
AB  - OBJECTIVE: The use of covered stents to close fenestration in total cavopulmonary
      connection is presented. METHODS: We retrospectively reviewed data of all
      patients undergoing the procedure of a covered stent to close fenestration of
      total cavopulmonary connection between 2005 and 2012. RESULTS: A total of 50
      patients met the inclusion criteria. Median age and weight were 7.7 years and 20
      kg, respectively. Median interval between Fontan completion and fenestration
      closure was 13 months. The femoral vein was used in 42 patients and the jugular
      vein in eight patients. Of the patients, seven received two stents. Covered
      stents were CP stents in 42 patients and Atrium Advanta V12 in eight patients.
      BIB balloons were used in 24 patients and simple balloons in 18 patients.
      Simultaneous occlusion of venous collaterals was observed in five patients.
      Median procedural and fluoroscopy times were 49 and 8 minutes, respectively. Mean
      central venous pressure rose from 10 to 12 mmHg. Mean oxygen saturation increased
      from 88% to 96%. Full occlusion was confirmed in 47 patients. The remaining had
      residual shunts: two patients had intracardiac Fontan, and one patient had a
      stent that could not be fully opened. Following the procedure, five patients had
      local bleeding, and three delayed discharge 48 hours after the procedure. There
      was no thromboembolic event after a mean follow-up of 49 months. CONCLUSION:
      Covered stent is a good option to close fenestration in extracardiac total
      cavopulmonary connection. It is safe, easily achievable with low fluoroscopy
      time, with very low risk of complication or failure. Good results are sustainable
      when excluding patients with none circular pathway.

PMID- 24915000
TI  - MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer
      by directly targeting Pin1.
AB  - Upregulation of Pin1 was shown to advance the functioning of several oncogenic
      pathways. It was recently shown that Pin1 is potentially an excellent prognostic
      marker and can also serve as a novel therapeutic target for prostate cancer.
      However, the molecular mechanism of Pin1 overexpression in prostate cancer is
      still unclear. In the present study, we showed that the mRNA expression levels of
      Pin1 were not correlated with Pin1 protein levels in prostate cell lines which
      indicated that Pin1 may be regulated at the post-transcriptional level. A key
      player in post-transcriptional regulation is represented by microRNAs (miRNAs)
      that negatively regulate expressions of protein-coding genes at the post
      transcriptional level. A bioinformatics analysis revealed that miR-296-5p has a
      conserved binding site in the Pin1 3'-untranslated region (UTR). A luciferase
      reporter assay demonstrated that the seed region of miR-296-5p directly interacts
      with the 3'-UTR of Pin1 mRNA. Moreover, miR-296-5p expression was found to be
      inversely correlated with Pin1 expression in prostate cancer cell lines and
      prostate cancer tissues. Furthermore, restoration of miR-296-5p or the knockdown
      of Pin1 had the same effect on the inhibition of the ability of cell
      proliferation and anchorage-independent growth of prostate cancer cell lines. Our
      results support miR-296-5p playing a tumor-suppressive role by targeting Pin1 and
      implicate potential effects of miR-296-5p on the prognosis and clinical
      application to prostate cancer therapy. 

PMID- 24915001
TI  - Genome elimination: translating basic research into a future tool for plant
      breeding.
AB  - During the course of our history, humankind has been through different periods of
      agricultural improvement aimed at enhancing our food supply and the performance
      of food crops. In recent years, it has become apparent that future crop
      improvement efforts will require new approaches to address the local challenges
      of farmers while empowering discovery across industry and academia. New plant
      breeding approaches are needed to meet this challenge to help feed a growing
      world population. Here I discuss how a basic research discovery is being
      translated into a potential future tool for plant breeding, and share the story
      of researcher Simon Chan, who recognized the potential application of this new
      approach--genome elimination--for the breeding of staple food crops in Africa and
      South America.

PMID- 24915002
TI  - Synthesis and biological evaluation of novel naphthalene compounds as potential
      antidepressant agents.
AB  - In this study, a series of novel naphthalene compounds were synthesized and
      screened for their antidepressant-like activities in vitro and in vivo. Their
      values for two descriptors (ClogP, tPSA) of the blood-brain barrier (BBB) were
      calculated for early assessment of the central nervous system (CNS) drug
      likeness. Seven of them (6d, 6i, 6k, 6o, 6p, 6s and 6t) demonstrated potential
      protective effects on corticosterone-induced lesion of PC12 cells although they
      cannot repair the irreversible oxidant injury to PC12 cells by hydrogen peroxide.
      Compounds with promising neurorestorative activities (6k, 6o and 6p) were further
      evaluated for their in vivo effects by forced swim test (FST) and open field test
      (OFT) in C57 mice models. The FST results showed that compounds 6k, 6o and 6p
      remarkably reduced the immobility time of the tested mice. Among them, compound
      6k was the most potent one, much more effective than Agomelatine and comparable
      to Fluoxetine. The OFT results showed that mice treated with compound 6k traveled
      a longer distance than those treated with Agomelatine or Fluoxetine, indicating a
      better general locomotor activity. The paper also proposed a possible binding
      mode of compound 6k with glucocorticoid receptor by docking study. The in vitro
      cytotoxicity data on HEK293 and L02 cells suggested compound 6k to be a promising
      antidepressant candidate for subsequent investigation.

PMID- 24915003
TI  - Probing of primed and unprimed sites of calpains: Design, synthesis and
      evaluation of epoxysuccinyl-peptide derivatives as selective inhibitors.
AB  - Calpains are intracellular cysteine proteases with important physiological
      functions. Up- or downregulation of their expression can be responsible for
      several diseases, therefore specific calpain inhibitors may be considered as
      promising candidates for drug discovery. In this paper we describe the synthesis
      and characterization of a new class of inhibitors derived from the analysis of
      amino acid preferences in primed and unprimed sites of calpains by incorporation
      of l- or d-epoxysuccinyl group (Eps). Amino acids for replacement were chosen by
      considering the substrate preference of calpain 1 and 2 enzymes. The compounds
      were characterized by RP-HPLC, amino acid analysis and ESI-MS. Selectivity of the
      compounds was studied by using calpain 1 and 2; and cathepsin B. We have
      identified five calpain specific inhibitors with different extent of selectivity.
      Two of these also exhibited isoform selectivity. Compound NH2-Thr-Pro-Leu-(d-Eps)
      Thr-Pro-Pro-Pro-Ser-NH2 proved to be a calpain 2 enzyme inhibitor with at least
      11.8-fold selectivity, while compound NH2-Thr-Pro-Leu-(l-Eps)-Ser-Pro-Pro-Pro-Ser
      NH2 possesses calpain 1 enzyme inhibition with at least 4-fold selectivity. The
      results of molecular modeling calculations suggest that the orientation of the
      bound inhibitor in the substrate binding cleft is markedly dependent on the
      stereochemistry of the epoxysuccinyl group. 

PMID- 24915005
TI  - Benefits and risks of anticoagulation resumption following traumatic brain
      injury.
AB  - IMPORTANCE: The increased risk of hemorrhage associated with anticoagulant
      therapy following traumatic brain injury creates a serious dilemma for medical
      management of older patients: Should anticoagulant therapy be resumed after
      traumatic brain injury, and if so, when? OBJECTIVE: To estimate the risk of
      thrombotic and hemorrhagic events associated with warfarin therapy resumption
      following traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective analysis of administrative claims data for Medicare beneficiaries
      aged at least 65 years hospitalized for traumatic brain injury during 2006
      through 2009 who received warfarin in the month prior to injury (n = 10,782).
      INTERVENTION: Warfarin use in each 30-day period following discharge after
      hospitalization for traumatic brain injury. MAIN OUTCOMES AND MEASURES: The
      primary outcomes were hemorrhagic and thrombotic events following discharge after
      hospitalization for traumatic brain injury. Hemorrhagic events were defined on
      inpatient claims using International Classification of Diseases, Ninth Revision,
      Clinical Modification codes and included hemorrhagic stroke, upper
      gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic
      events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and
      myocardial infarction. A composite of hemorrhagic or ischemic stroke was a
      secondary outcome. RESULTS: Medicare beneficiaries with traumatic brain injury
      were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3
      (7.3) years, and 82% had atrial fibrillation. Over the 12 months following
      hospital discharge, 55% received warfarin during 1 or more 30-day periods. We
      examined the lagged effect of warfarin use on outcomes in the following period.
      Warfarin use in the prior period was associated with decreased risk of thrombotic
      events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of
      hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior
      period was associated with decreased risk of hemorrhagic or ischemic stroke (RR,
      0.83 [95% CI, 0.72-0.96]). CONCLUSIONS AND RELEVANCE: Results from this study
      suggest that despite increased risk of hemorrhage, there is a net benefit for
      most patients receiving anticoagulation therapy, in terms of a reduction in risk
      of stroke, from warfarin therapy resumption following discharge after
      hospitalization for traumatic brain injury.

PMID- 24915006
TI  - Geographic and racial variation in asthma prevalence and emergency department use
      among Medicaid-enrolled children in 14 southern states.
AB  - BACKGROUND: Despite evidence-based prevention and practice guidelines, asthma
      prevalence, treatment, and outcomes vary widely at individual and community
      levels. Asthma disproportionate/ly affects low-income and minority children, who
      comprise a large segment of the Medicaid population. METHODS: 2007 Medicaid
      claims data from 14 southern states was mapped for 556 counties to describe the
      local area variation in 1-year asthma prevalence rates, emergency department (ED)
      visit rates, and racial disparity rate ratios. RESULTS: One-year period
      prevalence of asthma ranged from 2.8% in Florida to 6.4% in Alabama, with a
      median prevalence rate of 4.1%. At the county level, the prevalence was higher
      for Black children and ranged from 1.03% in Manatee County, FL, to 21.0% in
      Hockley County, TX. Black-White rate ratios of prevalence ranged from 0.49 in
      LeFlore County, MS, to 3.87 in Flagler County, FL. Adjusted asthma ED visit rates
      ranged from 2.2 per 1000 children in Maryland to 16.5 in Alabama, with a median
      Black-White ED-visit rate ratio of 2.4. Rates were higher for Black children,
      ranging from 0.80 per 1000 in Wicomico County, MD, to 70 per 1000 in DeSoto
      County, FL. Rate ratios of ED visits ranged from 0.25 in Vernon Parish, LA, to
      25.28 in Nelson County, KY. CONCLUSIONS AND RELEVANCE: Low-income children with
      Medicaid coverage still experience substantial variation in asthma prevalence and
      outcomes from one community to another. The pattern of worse outcomes for Black
      children also varies widely across counties. Eliminating this variation could
      substantially improve overall outcomes and eliminate asthma disparities.

PMID- 24915004
TI  - Artemisia scoparia enhances adipocyte development and endocrine function in vitro
      and enhances insulin action in vivo.
AB  - BACKGROUND: Failure of adipocytes to expand during periods of energy excess can
      result in undesirable metabolic consequences such as ectopic fat accumulation and
      insulin resistance. Blinded screening studies have indicated that Artemisia
      scoparia (SCO) extracts can enhance adipocyte differentiation and lipid
      accumulation in cultured adipocytes. The present study tested the hypothesis that
      SCO treatment modulates fat cell development and function in vitro and insulin
      sensitivity in adipose tissue in vivo. METHODS: In vitro experiments utilized a
      Gal4-PPARgamma ligand binding domain (LBD) fusion protein-luciferase reporter
      assay to examine PPARgamma activation. To investigate the ability of SCO to
      modulate adipogenesis and mature fat cell function in 3T3-L1 cells, neutral lipid
      accumulation, gene expression, and protein secretion were measured by Oil Red O
      staining, qRT-PCR, and immunoblotting, respectively. For the in vivo experiments,
      diet-induced obese (DIO) C57BL/6J mice were fed a high-fat diet (HFD) or HFD
      containing 1% w/w SCO for four weeks. Body weight and composition, food intake,
      and fasting glucose and insulin levels were measured. Phospho-activation and
      expression of insulin-sensitizing proteins in epididymal adipose tissue (eWAT)
      were measured by immunoblotting. RESULTS: Ethanolic extracts of A. scoparia
      significantly activated the PPARgamma LBD and enhanced lipid accumulation in
      differentiating 3T3-L1 cells. SCO increased the transcription of several
      PPARgamma target genes in differentiating 3T3-L1 cells and rescued the negative
      effects of tumor necrosis factor alpha on production and secretion of adiponectin
      and monocyte chemoattractant protein-1 in fully differentiated fat cells. DIO
      mice treated with SCO had elevated adiponectin levels and increased
      phosphorylation of AMPKalpha in eWAT when compared to control mice. In SCO
      treated mice, these changes were also associated with decreased fasting insulin
      and glucose levels. CONCLUSION: SCO has metabolically beneficial effects on
      adipocytes in vitro and adipose tissue in vivo, highlighting its potential as a
      metabolically favorable botanical supplement.

PMID- 24915007
TI  - Onset of aquaporin-4 expression in the developing mouse brain.
AB  - The main water channel in the brain, aquaporin-4 (AQP4) is involved in
      maintaining homeostasis and water exchange in the brain. In adult mammalian
      brains, it is expressed in astrocytes, mainly, and in high densities in the
      membranes of perivascular and subpial endfeet. Here, we addressed the question
      how this polarized expression is established during development. We used
      immunocytochemistry against AQP4, zonula occludens protein-1, glial fibrillary
      acidic protein, and beta-dystroglycan to follow astrocyte development in E15 to
      P3 NMRI mouse brains, and expression of AQP4. In addition we used freeze-fracture
      electron microscopy to detect AQP4 in the form of orthogonal arrays of particles
      (OAPs) on the ultrastructural level. We analyzed ventral, lateral, and dorsal
      regions in forebrain sections and found AQP4 immunoreactivity to emerge at E16
      ventrally before lateral (E17) and dorsal (E18) areas. AQP4 staining was spread
      over cell processes including radial glial cells in developing cortical areas and
      became restricted to astroglial endfeet at P1-P3. This was confirmed by double
      labeling with GFAP. In freeze-fracture replicas OAPs were found with a slight
      time delay but with a similar ventral to dorsal gradient. Thus, AQP4 is expressed
      in the embryonic mouse brain starting at E16, earlier than previously reported.
      However a polarized expression necessary for homeostatic function and water
      balance emerges at later stages around and after birth. 

PMID- 24915009
TI  - A comparative study between Solenopsis invicta and Solenopsis richteri on
      tolerance to heat and desiccation stresses.
AB  - Solenopsis invicta and Solenopsis richteri are two very closely related invasive
      ant species; however, S. invicta is a much more successful invader. Physiological
      tolerance to abiotic stress has been hypothesized to be important to the success
      of an invasive species. In this study, we tested the hypothesis that S. invicta
      is more tolerant to heat and desiccation stress than S. richteri. The data
      strongly support our hypothesis. S. invicta was found to be significantly less
      vulnerable than S. richteri to both heat and desiccation stress. Despite S.
      richteri having significantly higher body water content, S. invicta was less
      sensitive to desiccation stress due to its significantly lower water loss rate
      (higher desiccation resistance). After the cuticular lipid was removed, S.
      invicta still had a significantly lower water loss rate than S. richteri,
      indicating that cuticular lipids were not the only factors accounting for
      difference in the desiccation resistance between these two species. Since
      multiple biological and/or ecological traits can contribute to the invasion
      success of a particular species, whether the observed difference in tolerance to
      heat and desiccation stresses is indeed associated with the variation in invasion
      success between these two species can only be confirmed by further extensive
      comparative study. 

PMID- 24915008
TI  - Laminin alpha2-mediated focal adhesion kinase activation triggers Alport
      glomerular pathogenesis.
AB  - It has been known for some time that laminins containing alpha1 and alpha2
      chains, which are normally restricted to the mesangial matrix, accumulate in the
      glomerular basement membranes (GBM) of Alport mice, dogs, and humans. We show
      that laminins containing the alpha2 chain, but not those containing the alpha1
      chain activates focal adhesion kinase (FAK) on glomerular podocytes in vitro and
      in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM
      rendering these mice more susceptible to biomechanical strain in the glomerulus,
      also show progressive accumulation of alpha2 laminins in the GBM, and podocyte
      FAK activation. Analysis of glomerular mRNA from both models demonstrates
      significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in
      Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA
      knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9,
      MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small
      molecule inhibitor of FAK activation, ameliorated fibrosis and
      glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen
      levels, and partially restored GBM ultrastructure. Glomerular expression of MMP
      9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals.
      Collectively, this work identifies laminin alpha2-mediated FAK activation in
      podocytes as an important early event in Alport glomerular pathogenesis and
      suggests that FAK inhibitors, if safe formulations can be developed, might be
      employed as a novel therapeutic approach for treating Alport renal disease in its
      early stages. 

PMID- 24915011
TI  - Characterization of dry eye disease in diabetic patients versus nondiabetic
      patients.
AB  - PURPOSE: The purpose of this investigation was to assess the presence and
      relative severity of dry eye evaluated by a panel of diagnostic methods in
      diabetic patients as compared with that in nondiabetic patients. METHODS:
      Patients (>=40 years of age) scheduled for a routine eye examination at the
      clinical site were recruited for the study. Exclusion criteria included current
      use of topical medication for glaucoma or prior ocular surgery if the patient was
      within the postoperative recovery period (3 months). Study endpoints included
      tear film break-up time, tear film osmolarity, corneal fluorescein and
      conjunctival lissamine green staining, Schirmer strip testing, Ocular Surface
      Disease Index questionnaire, and Dry Eye International Task Force severity
      ranking. RESULTS: Sixty-three patients were enrolled in this study, 38 in the
      diabetic group and 25 in the nondiabetic group. All enrolled patients scored at
      least a 1 on the International Task Force ranking scale. A significantly higher
      mean tear film osmolarity was observed in the nondiabetic patient group, 312
      versus 303 mOsm/L (P = 0.02). The mean conjunctival staining scores were
      significantly higher in the diabetic patient group, 2.72 versus 2.11 (P = 0.034).
      No statistically significant differences were observed between patient groups for
      corneal staining, tear film break-up time, Schirmer strip, or Ocular Surface
      Disease Index scores. CONCLUSIONS: The overall presence and severity of dry eye
      was found to be similar in the diabetic and nondiabetic patient groups. However,
      significant differences were observed between groups with regard to individual
      diagnostic assessments (lissamine green staining and tear film osmolarity).

PMID- 24915010
TI  - Analysis of oxidative stress status, catalase and catechol-O-methyltransferase
      polymorphisms in Egyptian vitiligo patients.
AB  - Vitiligo is the most common depigmentation disorder of the skin. Oxidative stress
      is implicated as one of the probable events involved in vitiligo pathogenesis
      possibly contributing to melanocyte destruction. Evidence indicates that certain
      genes including those involved in oxidative stress and melanin synthesis are
      crucial for development of vitiligo. This study evaluates the oxidative stress
      status, the role of catalase (CAT) and catechol-O-Methyltransferase (COMT) gene
      polymorphisms in the etiology of generalized vitiligo in Egyptians. Total
      antioxidant capacity (TAC) and malondialdehyde (MDA) levels as well as CAT exon 9
      T/C and COMT 158 G/A polymorphisms were determined in 89 patients and 90 age and
      sex-matched controls. Our results showed significantly lower TAC along with
      higher MDA levels in vitiligo patients compared with controls. Meanwhile,
      genotype and allele distributions of CAT and COMT polymorphisms in cases were not
      significantly different from those of controls. Moreover, we found no association
      between both polymorphisms and vitiligo susceptibility. In conclusion, the
      enhanced oxidative stress with the lack of association between CAT and COMT
      polymorphisms and susceptibility to vitiligo in our patients suggest that
      mutations in other genes related to the oxidative pathway might contribute to the
      etiology of generalized vitiligo in Egyptian population. 

PMID- 24915012
TI  - Novel tear interferometer made of paper for lipid layer evaluation.
AB  - PURPOSE: To introduce a novel interferometer and provide clinical data based on
      its use. METHODS: Twenty-two normal subjects, 27 patients with dry eye syndrome,
      1 patient with obstructive meibomian gland dysfunction, and 2 patients with
      ocular graft-versus-host disease were included in the study. We cut a piece of
      copy paper to create an interferometer comprising a handle, a window, and an
      illumination area. The patient sits in front of a biomicroscope with his or her
      head fixed on the headrest. The examiner holds the handle of the interferometer
      10 mm from the front of the patient's eye. The examiner positions the
      illumination beam of the biomicroscope at the "illumination area." The examiner
      then observes a lipid layer interference pattern on the cornea through the
      window. RESULTS: For the normal subjects, wave or amorphous patterns with white
      or grey color were observed in interferometry. The mean estimated lipid layer
      thickness in the dry eye group (43 +/- 9 nm) was significantly thinner than that
      of the normal group (59 +/- 29 nm) (P = 0.021). For the patient with obstructive
      meibomian gland dysfunction, interferometry revealed a white interference pattern
      (30 nm). For ocular graft-versus-host disease, the lipid pattern was brown and
      blue (165 nm). Patients felt no discomfort, and no complications occurred during
      examination. CONCLUSIONS: We could successfully obtain photographs of the lipid
      layer pattern with this novel interferometer without additional equipment or
      cost. This interferometer may be useful for research regarding the
      pathophysiology, diagnosis, and treatment of dry eye.

PMID- 24915013
TI  - Mechanical sensitivity of the human conjunctiva.
AB  - PURPOSE: The aim of this study was to map the sensitivity of the marginal and
      other conjunctival regions and to investigate changes in the sensitivity of these
      regions when determined in the morning and evening. METHODS: Thirty-five healthy,
      noncontact lens wearers (20 female, 15 male; age 27.7 +/- 7.3 years) were
      enrolled. Mechanical sensitivity was measured at 8 locations on the ocular
      surface and adnexa (cornea, marginal, bulbar, and tarsal conjunctiva) using a
      Cochet-Bonnet esthesiometer (0.12-mm diameter filament). A subgroup of 11
      subjects (6 female, 5 male; age 28.9 +/- 9.9 years) returned after 12 hours when
      this protocol was repeated. RESULTS: The cornea was found to be the most
      sensitive region (all P < 0.001). The marginal conjunctiva showed greater
      sensitivity than did the bulbar and tarsal conjunctiva (all P < 0.001). The
      temporal marginal conjunctiva was more sensitive than the central marginal
      conjunctiva (all P < 0.05). No difference in marginal conjunctival sensitivity
      was found between upper and lower eyelids (all P > 0.05). The upper tarsal
      conjunctiva was more sensitive than the lower tarsal conjunctiva (P = 0.04).
      There was no significant difference in the sensitivity determined in the morning
      and the evening for any of the locations investigated (Bonferroni adjusted, P >
      0.006). CONCLUSIONS: This work has demonstrated that the marginal conjunctiva was
      the most sensitive of all the conjunctival regions and that this does not alter
      over the course of the day.

PMID- 24915014
TI  - Another look at the association between diabetes and keratoconus.
AB  - PURPOSE: The aim of this study was to evaluate the association between diabetes
      mellitus (DM) and keratoconus. METHODS: We conducted 2 substudies: (1)
      Retrospective comparison of the prevalence of DM in patients with keratoconus
      with that of control patients without keratoconus and (2) Cross-sectional study
      of the severity of keratoconus in diabetic keratoconus-affected patients and
      nondiabetic keratoconus-affected patients. Patients seen at the Wills Eye
      Hospital Cornea Service from January 2008 to August 2012 were included. Study 1
      included 1377 patients with keratoconus and 4131 controls without keratoconus.
      Study 2 involved 75 type 2 diabetic keratoconus-affected patients and 225
      nondiabetic keratoconus-affected patient, excluding patients with bilateral
      keratoplasty. In patients with a history of a corneal transplant in 1 eye, the
      other eye was included. Keratoconus severity was based on the topographic mean
      keratometry in the more severely affected eye. RESULTS: Two of 1377 (0.15%)
      keratoconus-affected patients had type 1 DM, which was similar to that of 20 of
      the 4131 (0.49%) matched controls (P = 0.139). The prevalence of type 2 DM was
      higher in patients with keratoconus (93/1377, 6.75%) than in matched controls
      (200/4131, 4.84%) (P = 0.005). When categorized by age group, the prevalence of
      type 2 DM was higher in patients with keratoconus than in those without
      keratoconus in patients aged between 25 and 44 years (P = 0.036) and 45 and 64
      years (P = 0.047). Using multinomial logistic regression analyses, the
      probability/risk of being in the severe keratoconus-affected group as opposed to
      the mild keratoconus-affected group was higher in patients with DM than in those
      without DM (P = 0.006; odds ratio = 2.691; 95% confidence interval, 1.330-5.445).
      CONCLUSIONS: There may be a positive association between type 2 DM and the
      presence and severity of keratoconus.

PMID- 24915015
TI  - Three-year outcome of Descemet stripping automated endothelial keratoplasty for
      bullous keratopathy after argon laser iridotomy.
AB  - PURPOSE: The aim of this study was to evaluate the 3-year outcome of Descemet
      stripping automated endothelial keratoplasty (DSAEK) for the treatment of bullous
      keratopathy secondary to argon laser iridotomy (ALI). METHODS: A total of 22
      consecutive patients (22 eyes) with ALI who underwent DSAEK were retrospectively
      analyzed. Best spectacle-corrected visual acuity (BSCVA), endothelial cell
      density, and complications were investigated over 3 years postoperatively. The
      outcome of DSAEK was also compared between the ALI group and 21 other patients
      with Fuchs endothelial dystrophy (FED) or pseudophakic bullous keratopathy (PBK)
      (FED/PBK group). RESULTS: The median BSCVA improved from logarithm of the minimum
      angle of resolution 1.40 before DSAEK to 0.30 at 6 months, 0.30 at 12 months,
      0.22 at 24 months, and 0.15 at 36 months after surgery. The median endothelial
      cell loss was 20.3% at 6 months, 18.4% at 12 months, 32.5% at 24 months, and
      46.5% at 36 months. Comparison of the ALI group with the FED/PBK group showed no
      significant difference in the BSCVA or endothelial cell density. Rejection
      affected 9.1% of the ALI group versus 0% of the FED/PBK group (P = 0.49), the
      graft dislocation rate was 0% versus 9.5% (P = 0.23), and posterior synechiae
      were found in 31.8% versus 4.8% (P = 0.046). CONCLUSIONS: The 3-year outcome of
      DSAEK for bullous keratopathy after ALI was excellent. However, caution should be
      exercised in patients with a history of ALI to avoid posterior synechiae after
      DSAEK.

PMID- 24915016
TI  - Efficacy and safety of combination treatment for oculodermal melanocytosis:
      surgical reduction and use of 532-nm Q-switched Nd: YAG laser.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and safety of
      combination treatment using surgical reduction technique and 532-nm Q-switched
      Nd:YAG laser treatment for the removal of oculodermal melanocytosis. METHODS: We
      retrospectively reviewed the medical records of patients who underwent
      combination treatment using surgical reduction and 532-nm Q-switched Nd:YAG laser
      for the removal of ocular pigmentation in oculodermal melanocytosis at Asan
      Medical Center (Seoul, Korea) between January 2009 and January 2013. The safety
      and cosmetic efficacy of this new surgical strategy were assessed by both
      patients and observers. RESULTS: Fifty eyes of 47 patients with oculodermal
      melanocytosis were enrolled. Ocular pigmentation was successfully reduced in all
      patients, and all patients were satisfied with the cosmetic results at the last
      visit. Preoperative and postoperative corrected visual acuity, keratometry, and
      refractive errors did not significantly differ. Postoperative intraocular
      pressure was significantly reduced (mean change, 2.33 +/- 3.54 mm Hg; P = 0.03)
      at 1 month after surgery. During the follow-up period, no serious adverse events
      developed other than conjunctival neovascularization and conjunctival inclusion
      cyst in 5 eyes, respectively. CONCLUSIONS: Combination treatment for oculodermal
      melanocytosis removal seems to be cosmetically satisfactory and safe. This study
      suggested that combination treatment using surgical technique and 532-nm Q
      switched Nd:YAG laser may be helpful for the removal of oculodermal
      melanocytosis.

PMID- 24915017
TI  - Graft survival versus glaucoma treatment after penetrating or Descemet stripping
      automated endothelial keratoplasty.
AB  - PURPOSE: The aim of this study was to assess and compare the association of
      glaucoma therapy with graft survival after performing penetrating keratoplasty
      (PKP) and Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS:
      A retrospective chart review was performed of cases: primary PKP from January 1,
      2003, to December 31, 2005, or primary DSAEK from January 1, 2006, to December
      31, 2008. Eyes with a surgical indication of pseudophakic corneal edema were
      included in the statistical analysis. Eyes were stratified by glaucoma treatment
      into those with (1) no glaucoma treatment, (2) medical therapy only, or (3)
      surgical intervention. The main outcome measure was graft survival. RESULTS:
      Fifty-seven PKP-operated and 156 DSAEK-operated eyes met the inclusion criteria.
      After PKP and DSAEK, respectively, the 5-year Kaplan-Meier graft survival was
      94.7% and 93.8% in eyes with no glaucoma treatment (P > 0.99), 93.8% and 96.3% in
      eyes with medical therapy only (P > 0.99), and 56.8% and 50% in eyes with
      surgical intervention (P > 0.99). After both procedures were performed, graft
      survival was significantly worse in eyes with surgical intervention compared with
      that in eyes with no glaucoma treatment (P < 0.0001) or in eyes with medical
      therapy alone (P < 0.0001). CONCLUSIONS: PKP and DSAEK have comparable graft
      survival in eyes without glaucoma management and in those with comparable
      glaucoma management.

PMID- 24915018
TI  - Efficacy of hypotonic 0.18% sodium hyaluronate eye drops in patients with dry eye
      disease.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of hypotonic 0.18%
      sodium hyaluronate (SH) eye drops under the clinical settings of the dry eye
      workshop treatment guideline for mild dry eye disease (DED). METHODS: This
      analysis included 60 patients with DED. Patients with level 1 DED were treated
      with either isotonic 0.1% SH (group 1) or with hypotonic 0.18% SH eye drops
      (group 2). Patients with level 2 DED were treated with 0.1% fluorometholone,
      0.05% cyclosporine A, and either isotonic 0.1% SH (group 3) or hypotonic 0.18% SH
      (group 4) eye drops. Tear film breakup time (TBUT), Schirmer test, corneal
      staining with fluorescein, and ocular surface disease index score were recorded
      at baseline, 1 month, and 3 months after treatment. RESULTS: In group 2, TBUT at
      3 months (P = 0.03) and corneal staining scores at 1 and 3 months (P <= 0.03)
      were significantly improved after the treatment compared with baseline scores,
      whereas these parameters were not changed during the follow-up period in group 1.
      In groups 3 and 4, TBUT and corneal staining scores at 1 and 3 months, and ocular
      surface disease index score and Schirmer test results at 3 months after the
      treatment showed significant improvements compared with the baseline score (P <
      0.05). Group 4 patients showed an extended TBUT and an improved corneal staining
      score (P <= 0.01) at 3 months after treatment, compared with the values of group
      3. CONCLUSIONS: Hypotonic 0.18% SH eye drops seemed to be effective in improving
      tear film stability and ocular surface integrity compared with isotonic 0.1% SH
      eye drops in patients with mild DED.

PMID- 24915019
TI  - Retained host Descemet membrane (Auto-DMET) during conversion of deep anterior
      lamellar keratoplasty to penetrating keratoplasty: a case report.
AB  - PURPOSE: The aim of this study was to relate a case of deep anterior lamellar
      keratoplasty (DALK) converted to penetrating keratoplasty in which the host
      central Descemet membrane (DM) with a large perforation was left attached to the
      host cornea. METHODS: This is a case report of a 34-year-old man who underwent an
      attempted DALK for keratoconus in his left eye, which became complicated with a
      large rupture in DM during dissection. The host DM was left in place, the donor
      cornea with DM intact was sutured onto the host bed, and air was injected into
      the anterior chamber. The patient was monitored by biomicroscopy, pachymetry,
      topography, anterior segment optical coherence tomography, and specular
      microscopy. RESULTS: The postoperative course resulted in improved uncorrected
      visual acuity, best spectacle-corrected visual acuity, and topography. Corneal
      edema was observed in the host cornea peripheral to the graft. Three months after
      the surgery, the endothelial cell density was reduced by 63% compared with the
      preoperative donor cell density. CONCLUSIONS: Leaving the host DM during
      conversion of DALK to penetrating keratoplasty was uneventful in this case,
      although corneal edema was observed in the area overlying the host cornea. It is
      possible that the retained DM could provide additional autologous endothelial
      cells to prolong graft survival.

PMID- 24915022
TI  - Novel Garnet-structure Ca(2)GdZr(2)(AlO(4))3:Ce(3+) phosphor and its structural
      tuning of optical properties.
AB  - Aluminate garnet phosphors Ca2GdZr2(AlO4)3:Ce(3+) (CGZA:Ce(3+)) for solid-state
      white lighting sources are reported. The crystal structure and Mulliken bonding
      population of the CGZA:Ce(3+) have been analyzed. The larger 5d ((2)D) barycenter
      shift epsilonc and smaller phenomenological parameter 10Dq of Ce(3+) in CGZA are
      related to the larger covalent character of Ce-O. The tuning spectral properties
      of the Ce(3+)-doped CGZA-based isostructural phosphors are presented. The
      splitting of cubic crystal field energy level (2)Eg in Ca2REZr2(AlO4)3:Ce(3+)
      (CREZA:Ce(3+)) (RE = Lu, Y, and Gd) increases as the radius of RE(3+) increases,
      and the splitting of (2)Eg may dominate the difference of spectroscopic red-shift
      D(A) in CREZA:Ce(3+). The splitting of the (2)Eg in CaGd2ZrSc(AlO4)3:Ce(3+)
      (CGZSA:Ce(3+)) phosphors increases seemly due to the decreasing of the covalent
      character of Ce-O. Thermal quenching properties of Ce(3+)-doped CGZA-based
      isostructural phosphors are also presented and analyzed. For CREZA:Ce(3+)
      phosphors, the increasing of the radius of RE(3+) results in an enhancement of
      thermal quenching. The quenching of CGZSA:Ce(3+) is obviously stronger mainly due
      to the smaller energy difference between the lowest 5d excited state and 4f
      ground state. 

PMID- 24915020
TI  - Peptidoglycan architecture of Gram-positive bacteria by solid-state NMR.
AB  - Peptidoglycan is an essential component of cell wall in Gram-positive bacteria
      with unknown architecture. In this review, we summarize solid-state NMR
      approaches to address some of the unknowns in the Gram-positive bacteria
      peptidoglycan architecture: 1) peptidoglycan backbone conformation, 2) PG-lattice
      structure, 3) variations in the peptidoglycan architecture and composition, 4)
      the effects of peptidoglycan bridge-length on the peptidoglycan architecture in
      Fem mutants, 5) the orientation of glycan strands with respect to the membrane,
      and 6) the relationship between the peptidoglycan structure and the glycopeptide
      antibiotic mode of action. Solid-state NMR analyses of Staphylococcus aureus cell
      wall show that peptidoglycan chains are surprisingly ordered and densely packed.
      The peptidoglycan disaccharide backbone adopts 4-fold screw helical symmetry with
      the disaccharide unit periodicity of 40A. Peptidoglycan lattice in the S. aureus
      cell wall is formed by cross-linked PG stems that have parallel orientations. The
      structural characterization of Fem-mutants of S. aureus with varying lengths of
      bridge structures suggests that the PG-bridge length is an important determining
      factor for the PG architecture.

PMID- 24915021
TI  - Structural dynamics of dendritic spines: molecular composition, geometry and
      functional regulation.
AB  - The development of dendritic spines with specific geometry and membrane
      composition is critical for proper synaptic function. Specific spine membrane
      architecture, sub-spine microdomains and spine head and neck geometry allow for
      well-coordinated and compartmentalized signaling, disruption of which could lead
      to various neurological diseases. Research from neuronal cell culture, brain
      slices and direct in vivo imaging indicates that dendritic spine development is a
      dynamic process which includes transition from small dendritic filopodia through
      a series of structural refinements to elaborate spines of various morphologies.
      Despite intensive research, the precise coordination of this morphological
      transition, the changes in molecular composition, and the relation of spines of
      various morphologies to function remain a central enigma in the development of
      functional neuronal circuits. Here, we review research so far and aim to provide
      insight into the key events that drive structural change during transition from
      immature filopodia to fully functional spines and the relevance of spine geometry
      to function. 

PMID- 24915023
TI  - Effects of domain-specific noise on visual motion processing in schizophrenia.
AB  - BACKGROUND: Visual perception impairments in schizophrenia stem from abnormal
      information processing. Information processing requires neural response to a
      stimulus (signal) against a backdrop of 1) random variation in baseline neural
      activity (internal noise) and sometimes irrelevant environmental stimulation
      (external noise). Filtering out noise is a critical aspect of information
      processing, and needs to be critically examined in schizophrenia. METHODS: To
      understand how noise in the visual system constrains perceptual processing, we
      devised a novel paradigm to build in both signal and external noise on same
      visual stimulus. Here, instead of uniformed noise, domain-specific noise-
      variations in stimulus speed--was introduced to evaluate the performance of
      schizophrenia patients in speed discrimination. Each motion stimulus--a random
      dot pattern (RDP) comprising 200 moving dots--included a range of speeds, drawn
      individually from a Gaussian distribution for each dot. The task for patients (n
      = 26) and controls (n = 28) was to identify which of two stimuli moved faster
      based on their mean speeds. FINDINGS: Patients exhibited deficient speed
      discrimination at baseline, in the absence of speed noise. Their speed
      discrimination was further degraded in the presence of low and medium levels of
      external noise. In the presence of a high levels of noise, degradation of
      patients' speed discrimination leveled-off, resulting in similar performance to
      controls. CONCLUSION: These domain-specific noise effects on speed discrimination
      provide direct evidence for the existence of heightened internal noise within a
      specific visual motion processing domain in schizophrenia.

PMID- 24915024
TI  - The effect of additives on the zinc carbenoid-mediated cyclopropanation of a
      dihydropyrrole.
AB  - The synthesis of a key intermediate in the preparation of oral antidiabetic drug
      Saxagliptin is discussed with an emphasis on the challenges posed by the
      cyclopropanation of a dihydropyrrole. Kinetic studies on the cyclopropanation
      show an induction period that is consistent with a change in the structure of the
      carbenoid reagent during the course of the reaction. This mechanistic transition
      is associated with an underlying Schlenk equilibrium that favors the formation of
      monoalkylzinc carbenoid IZnCH2I relative to dialkylzinc carbenoid Zn(CH2I)2,
      which is responsible for the initiation of the cyclopropanation. The factors
      influencing reaction rates and diastereoselectivities are discussed with the aid
      of DFT computational studies. The rate accelerations observed in the presence of
      Bronsted acid-type additives correlate with the minimization of the undesired
      induction period and offer insights for the development of a robust process. 

PMID- 24915025
TI  - Profound reduction in the tamoxifen active metabolite endoxifen in a patient on
      phenytoin for epilepsy compared with a CYP2D6 genotype matched cohort.
AB  - Tamoxifen is a prodrug, requiring cytochrome P450 enzyme-mediated metabolism to
      form the active metabolite endoxifen. We identified a case of drug-drug
      interaction involving tamoxifen and phenytoin, associated with a markedly lower
      endoxifen level than predicted. The patient is a 49-year-old woman, genotyped as
      a cytochrome P450 2D6 (CYP2D6) extensive metabolizer, chronically taking
      phenytoin for a seizure disorder. The plasma endoxifen level 2 months after
      starting tamoxifen was 4.72 nmol/l, the lowest level we have seen in our clinic
      among patients with CYP2D6 extensive metabolizer genotypes (n=195). To our
      knowledge, this is the first report documenting the extent of induction in terms
      of both tamoxifen and endoxifen levels during concomitant phenytoin therapy, and
      this effect would likely result in loss of therapeutic benefit from tamoxifen.
      Phenytoin should therefore not be used concurrently with tamoxifen for extended
      periods of time unless a therapeutic drug (endoxifen) monitoring strategy is
      utilized. 

PMID- 24915026
TI  - Botulinum toxin A, brain and pain.
AB  - Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a
      potential biological threat. At the same time, it is among the most widely used
      therapeutic proteins used yearly by millions of people, especially for cosmetic
      purposes. Currently, its clinical use in certain types of pain is increasing, and
      its long-term duration of effects represents a special clinical value. Efficacy
      of BoNT/A in different types of pain has been found in numerous clinical trials
      and case reports, as well as in animal pain models. However, sites and mechanisms
      of BoNT/A actions involved in nociception are a matter of controversy. In analogy
      with well known neuroparalytic effects in peripheral cholinergic synapses,
      presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting
      peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On
      the other hand, growing number of behavioral and immunohistochemical studies
      demonstrated the requirement of axonal transport for BoNT/A's antinociceptive
      action. In addition, toxin's enzymatic activity in central sensory regions was
      clearly identified after its peripheral application. Apart from general
      pharmacology, this review summarizes the clinical and experimental evidence for
      BoNT/A antinociceptive activity and compares the data in favor of peripheral vs.
      central site and mechanism of action. Based on literature review and published
      results from our laboratory we propose that the hypothesis of peripheral site of
      BoNT/A action is not sufficient to explain the experimental data collected up to
      now. 

PMID- 24915027
TI  - Some challenges with statistical inference in adaptive designs.
AB  - Adaptive designs have generated a great deal of attention to clinical trial
      communities. The literature contains many statistical methods to deal with added
      statistical uncertainties concerning the adaptations. Increasingly encountered in
      regulatory applications are adaptive statistical information designs that allow
      modification of sample size or related statistical information and adaptive
      selection designs that allow selection of doses or patient populations during the
      course of a clinical trial. For adaptive statistical information designs, a few
      statistical testing methods are mathematically equivalent, as a number of
      articles have stipulated, but arguably there are large differences in their
      practical ramifications. We pinpoint some undesirable features of these methods
      in this work. For adaptive selection designs, the selection based on biomarker
      data for testing the correlated clinical endpoints may increase statistical
      uncertainty in terms of type I error probability, and most importantly the
      increased statistical uncertainty may be impossible to assess. 

PMID- 24915028
TI  - [Therapeutic possibilities in refractory epilepsy in tuberous sclerosis complex].
AB  - INTRODUCTION: Tuberous sclerosis complex (TSC) is frequently accompanied by
      difficult-to-treat epilepsy, which conditions these patients' quality of life and
      cognitive level. AIM. To describe the epidemiological and clinical
      characteristics, as well as the treatment of patients affected by TSC with
      epilepsy. PATIENTS AND METHODS: A retrospective review was carried out of the
      medical records of 30 patients aged under 18 registered in our database, who had
      been diagnosed with TSC and epilepsy. RESULTS: The age at onset of epilepsy in
      the patients with TSC in our series ranged from one month to four years. All of
      them began with partial crises. Two presented West's syndrome and four others had
      infantile spasms without hypsarrhythmia. In 19 of the patients, the epilepsy was
      medication resistant. As regards treatment with antiepileptic drugs, 11 are in
      monotherapy, 10 in bitherapy, seven in tritherapy and one with four drugs. Two
      were given ACTH, two carry an implanted vagal nerve stimulator, four receive
      treatment with everolimus and eight have undergone surgery. CONCLUSIONS: Epilepsy
      is a very common problem and begins in the early years of life in TSC. There are
      currently a large number of therapeutic options available, although 63.3% of
      patients have non-controlled epilepsy and most of them present crises on a daily
      basis. Poor control of their crises is correlated with mental retardation and
      autism spectrum disorder. The positive response obtained with other therapeutic
      possibilities, such as mTOR pathway inhibitors, surgery and vagal nerve
      stimulator, should be noted.

PMID- 24915029
TI  - [Neurological examination in patients undergoing sedation with propofol: a
      descriptive study].
AB  - INTRODUCTION: The neurological examination is a resource used in evaluating
      patients who are in coma. Anaesthesia can be a factor that exerts an influence on
      the findings. We evaluated the examination of the comatose patient in the case of
      patients anaesthetised with propofol in order to define its clinical value.
      PATIENTS AND METHODS: A prospective study was conducted among those who had
      undergone heart surgery in the intensive care unit of a tertiary hospital during
      the months of April and May 2011. Aspects that were analysed were the examination
      of the anaesthetic coma, pharmacological or medical factors that can have an
      influence and a full neurological examination following recovery. Patients with
      previous neurological symptoms were excluded. RESULTS: Thirty patients were
      selected (16 males and 14 females); mean age: 72 +/- 10 years. All the patients
      were sedated with propofol. During sedation, 17 (46.7%) presented unreactive
      pupils. No spontaneous eye movements were observed in 100% of the sample. Ocular
      alterations in primary position were observed in 23.3% of them. Oculocephalic
      reflexes were absent in 93.3% and oculovestibular reflexes, in 100%; the corneal
      reflex, was absent in 70% (with asymmetry), as was the ciliospinal reflex, in
      83.3%. The algesic motor response was absent in 93.3%, as were the cutaneous
      plantar extensor reflexes, in 20%; and 66.7% were indifferent. Following
      anaesthesia, the neurological examination was normal in 80%, there were slight
      orientation impairments in 16.7% and a hemispheric syndrome was found in one
      patient. CONCLUSIONS: Anaesthesia with propofol alters the reversible cutaneous
      plantar, pupillary, trunk and motor response reflexes on withdrawing sedation.
      The alterations may be asymmetrical. Neurological examinations should not be used
      in the case of patients sedated with propofol in order to make clinical
      decisions.

PMID- 24915030
TI  - [Characterisation of factors associated with carotid stenosis in a population at
      high risk].
AB  - INTRODUCTION: Moderate to severe stenosis is the less prevalent among the forms
      of carotid atherosclerotic disease), but it carries a high risk of ischaemic
      stroke. AIM: To characterise factors associated with moderate to severe carotid
      stenosis in a high-risk population. PATIENTS AND METHODS: We performed an
      analysis on traditional risk factors associated with carotid stenosis >=50% in
      533 patients who received Doppler ultrasound due to a history of stroke (34%) or
      who had = 2 of the risk factors: age >=55 years (86%), hypertension (65%),
      dyslipidemia (52%), obesity (42%), diabetes (40%) or smoking (40%). RESULTS: The
      prevalence of carotid stenosis >=50% was 7.1%, symptomatic (associated with
      stroke in congruent territory) in 5.6%, bilateral in 2.1% and bilateral
      symptomatic in 1.5%. A 36.8% of patients had moderate to severe load (>=4) of
      atherosclerotic plaques (25.9% moderate: 4-6 plaques, and 10.9% severe: >=7
      plaques). By multivariate analysis we identified the age >=75 years,
      dyslipidemia, and smoking as factors independently associated with carotid
      stenosis >=50%, and hypertension and smoking with symptomatic stenosis. The
      number of risk factors was strongly associated with the prevalence of carotid
      stenosis. Notably, neither diabetes nor obesity explained the degree of moderate
      to severe carotid stenosis. CONCLUSIONS: As forms of carotid atherosclerotic
      disease, moderate to severe stenosis is less frequent than a high burden of
      atherosclerotic plaques. Advanced age, smoking, dyslipidemia and hypertension are
      the main traditional risk factors associated with the degree of carotid stenosis.

PMID- 24915031
TI  - [Refractory status epilepticus presenting as shaken baby syndrome].
AB  - INTRODUCTION: A convulsive status in infants is usually triggered by a febrile
      syndrome secondary to an intercurrent infection or an infection affecting the
      central nervous system. Shaken baby syndrome is characterised by its association
      with bilateral or multifocal haemorrhage, retinal haemorrhage and encephalopathy.
      Children under one year old are the group with the highest risk, with a maximum
      incidence reaching a peak between 10 and 16 weeks of age. Intercurrent processes,
      such as baby colic or febrile syndromes that tend to step up crying, are usually
      precipitating factors of shaking. CASE REPORTS: We present the cases of two
      infants who began with a status epilepticus within a context of a febrile
      syndrome. Imaging tests revealed bilateral subdural haematomas in different stage
      of progress and bilateral retinal haemorrhages were observed in the fundus oculi
      of both children. CONCLUSIONS: In a child with an unspecific febrile process that
      develops a convulsive status, the professional should suspect, in addition to
      more usual problems, shaken baby syndrome as a possible causation, above all if
      the child is under six months old.

PMID- 24915032
TI  - Biomarkers in multiple sclerosis: an update for 2014.
AB  - Multiple sclerosis is a chronic, demyelinating and inflammatory disease of the
      central nervous system that mainly affects young adults. It is characterised by
      processes involving inflammation, demyelination and axonal destruction, and as a
      result the pathogenic aspects and response to treatment of the disease vary
      widely. It is therefore difficult to establish a prognosis for these patients or
      to determine the effectiveness of the different drugs that are employed. Current
      clinical research into the development of new biomarkers has advanced a great
      deal in recent years, especially in the early stages of the disease. Yet, it is
      essential to further our knowledge about novel markers of the disease, and not
      only in the more advanced stages, so as to be able to stop disability from
      progressing and to establish new therapy regimens in these patients. This review
      presents an update on the information available about the biomarkers that are
      currently validated and used in multiple sclerosis, together with the possible
      candidates for utilisation in routine clinical practice. 

PMID- 24915033
TI  - [A variety of the face of the giant panda sign].

PMID- 24915034
TI  - [Tropical spastic paraparesis: a report of a new case in Spain].

PMID- 24915035
TI  - [Ulnar neuropathy in the elbow and Martin-Gruber anastomosis in four patients.
      The contribution made by ultrasound imaging].

PMID- 24915036
TI  - Clinical and laboratory parameters associated with multiple surgeries in children
      with acute hematogenous osteomyelitis.
AB  - BACKGROUND: In the era of methicillin-resistant Staphylococcus aureus, surgical
      intervention seems to be increasingly common as an adjunct to treatment for
      pediatric acute hematogenous osteomyelitis (AHO). The purpose of this study is to
      identify objective clinical and laboratory parameters that are associated with
      repeated surgical intervention during the acute phase of treatment. METHODS:
      Fifty-seven children who were consecutively evaluated and treated for AHO at a
      single institution during 2009 were studied retrospectively. Objective clinical
      and laboratory parameters related to length of hospitalization were recorded for
      each child. Univariate analysis was performed with ordinal logistic regression,
      chi, Fisher exact, and Wilcoxon rank-sum and 2-value tests to identify
      independent variables associated with the occurrence of surgery in children with
      AHO. Multivariate logistic regression was used to identify parameters associated
      with repeated surgical intervention. RESULTS: Sixteen children were treated with
      antibiotics alone and no surgery. There were 41 children who had at least 1
      surgery and 12 who underwent >=2 surgeries. Multiple logistic regression showed
      that a swollen extremity (P=0.002), initial C-reactive protein (CRP) value >9.9
      mg/dL (P=0.02), and respiration rate >27 breaths/min (P=0.02) were significantly
      associated with the occurrence of at least 1 surgery. The best model to identify
      the occurrence of repeated surgical intervention in children with AHO included:
      >=4 febrile days on antibiotics; and the CRP values at admission (>19.8 mg/dL),
      48 hours after the initial surgery (>21.5 mg/dL), and 96 hours after the initial
      surgery (>15.3 mg/dL). CONCLUSIONS: Children with AHO who have sustained marked
      elevation of CRP values during the first 96 hours after surgery and who remain
      febrile while on antibiotics have an increased likelihood of repeated surgical
      intervention and should be evaluated carefully for additional surgical treatment.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 24915037
TI  - In reply: bracing for adolescent idiopathic scoliosis in practice today.

PMID- 24915038
TI  - Copper radical oxidases and related extracellular oxidoreductases of wood-decay
      Agaricomycetes.
AB  - Extracellular peroxide generation, a key component of oxidative lignocellulose
      degradation, has been attributed to various enzymes including the copper radical
      oxidases. Encoded by a family of structurally related sequences, the genes are
      widely distributed among wood decay fungi including three recently completed
      polypore genomes. In all cases, core catalytic residues are conserved, but five
      subfamilies are recognized. Glyoxal oxidase, the most intensively studied
      representative, has been shown physiologically connected to lignin peroxidase.
      Relatively little is known about structure-function relationships among more
      recently discovered copper radical oxidases. Nevertheless, differences in
      substrate preferences have been observed in one case and the proteins have been
      detected in filtrates of various wood-grown cultures. Such diversity may reflect
      adaptations to host cell wall composition and changing environmental conditions. 

PMID- 24915040
TI  - Storylines in intercalation chemistry.
AB  - Intercalation chemistry will soon be a hundred years old. The period of greatest
      activity in this field of solid state chemistry and physics was from about 1970
      to 1990. The intercalation reactions are defined as topotactic solid state
      reactions and the products--the intercalation compounds--are clearly
      distinguished from inclusion and interstitial compounds. After a short historical
      introduction emphasizing the pioneering work of Ulrich Hofmann, the central
      topics and concepts will be reviewed and commented on. The most important ones,
      in my view, are: dichalcogenide intercalation compounds, the electrochemical
      intercalation and the search for new battery electrodes, the physics of graphite
      intercalation compounds, and the staging and interstratification phenomena. The
      relation to other fields of actual research and the demands for forthcoming
      research will also be addressed.

PMID- 24915039
TI  - Carfilzomib and oprozomib synergize with histone deacetylase inhibitors in head
      and neck squamous cell carcinoma models of acquired resistance to proteasome
      inhibitors.
AB  - Acquired resistance to proteasome inhibitors represents a considerable impediment
      to their effective clinical application. Carfilzomib and its orally bioavailable
      structural analog oprozomib are second-generation, highly-selective, proteasome
      inhibitors. However, the mechanisms of acquired resistance to carfilzomib and
      oprozomib are incompletely understood, and effective strategies for overcoming
      this resistance are needed. Here, we developed models of acquired resistance to
      carfilzomib in two head and neck squamous cell carcinoma cell lines, UMSCC-1 and
      Cal33, through gradual exposure to increasing drug concentrations. The resistant
      lines R-UMSCC-1 and R-Cal33 demonstrated 205- and 64-fold resistance,
      respectively, relative to the parental lines. Similarly, a high level of cross
      resistance to oprozomib, as well as paclitaxel, was observed, whereas only
      moderate resistance to bortezomib (8- to 29-fold), and low level resistance to
      cisplatin (1.5- to 5-fold) was seen. Synergistic induction of apoptosis signaling
      and cell death, and inhibition of colony formation followed co-treatment of
      acquired resistance models with carfilzomib and the histone deacetylase inhibitor
      (HDACi) vorinostat. Synergism was also seen with other combinations, including
      oprozomib plus vorinostat, or carfilzomib plus the HDACi entinostat. Synergism
      was accompanied by upregulation of proapoptotic Bik, and suppression of Bik
      attenuated the synergy. The acquired resistance models also exhibited elevated
      levels of MDR-1/P-gp. Inhibition of MDR-1/P-gp with reversin 121 partially
      overcame carfilzomib resistance in R-UMSCC-1 and R-Cal33 cells. Collectively,
      these studies indicate that combining carfilzomib or oprozomib with HDAC or MDR
      1/P-gp inhibitors may be a useful strategy for overcoming acquired resistance to
      these proteasome inhibitors. 

PMID- 24915041
TI  - Monitoring protein misfolding by site-specific labeling of proteins in vivo.
AB  - Incorporating fluorescent amino acids by suppression of the TAG amber codon is a
      useful tool for site-specific labeling of proteins and visualizing their
      localization in living cells. Here we use a plasmid encoded orthogonal
      tRNA/aminoacyl-tRNA synthetase pair to site-specifically label firefly luciferase
      with the environmentally sensitive fluorescent amino acid, 3-(6-acetylnaphthalen
      2-ylamino)-2- aminopropanoic acid (ANAP) and explore the detectability of
      conformational changes in labeled luciferase in the yeast cytoplasm. We find that
      ANAP labeling efficiency is greatly increased in [PSI+] cells and show that
      analysis of the ANAP fluorescence emission by confocal imaging allows for
      tracking the thermal unfolding and aggregation of luciferase in vivo. Furthermore
      we demonstrate that flow cytometry can be used to study conformational changes in
      luciferase and chaperone-mediated refolding in quantitative terms and at the
      level of single cells. This experimental setup for the first time allows for the
      direct analysis of the folding state of a protein in living cells and may serve
      as valuable new tool for examining mechanisms of protein folding, misfolding and
      aggregation. 

PMID- 24915042
TI  - Responses of the insulin signaling pathways in the brown adipose tissue of rats
      following cold exposure.
AB  - The insulin signaling pathway is critical for the control of blood glucose
      levels. Brown adipose tissue (BAT) has also been implicated as important in
      glucose homeostasis. The effect of short-term cold exposure on this pathway in
      BAT has not been explored. We evaluated the effect of 4 hours of cold exposure on
      the insulin pathway in the BAT of rats. Whole genomic microarray chips were used
      to examine the transcripts of the pathway in BAT of rats exposed to 4 degrees C
      and 22 degrees C for 4 hours. The 4 most significantly altered pathways following
      4 hours of cold exposure were the insulin signaling pathway, protein kinase A,
      PI3K/AKT and ERK/MAPK signaling. The insulin signaling pathway was the most
      affected. In the documented 142 genes of the insulin pathway, 42 transcripts
      (29.6%) responded significantly to this cold exposure with the least false
      discovery rate (Benjamini-Hochberg Multiple Testing: -log10 (p-value)  = 7.18).
      Twenty-seven genes (64%) were up-regulated, including the insulin receptor
      (Insr), insulin substrates 1 and 2 (Irs1 and Irs2). Fifteen transcripts (36%)
      were down-regulated. Multiple transcripts of the primary target and secondary
      effector targets for the insulin signaling were also up-regulated, including
      those for carbohydrate metabolism. Using western blotting, we demonstrated that
      the cold induced higher Irs2, Irs1, and Akt-p protein levels in the BAT than in
      the BAT of controls maintained at room temperature, and higher Akt-p protein
      level in the muscle. CONCLUSION: this study demonstrated that 4 hours of cold
      exposure stimulated the insulin signaling pathway in the BAT and muscle of
      overnight fasted rats. This raises the possibility that acute cold stimulation
      may have potential to improve glucose clearance and insulin sensitivity.

PMID- 24915043
TI  - Interaction of fluorescent dyes with DNA and spermine using fluorescence
      spectroscopy.
AB  - Oligonucleotides labelled with fluorescent dyes are widely used as probes for the
      identification of DNA sequences in detection methods using optical spectroscopies
      such as fluorescence and surface enhanced Raman scattering (SERS). Spermine is
      widely used in surface enhanced based assays as a charge reduction and
      aggregating agent as it interacts strongly with the phosphate backbone and has
      shown to enhance the signal of a labelled oligonucleotide. The fluorescence
      intensity of two commonly used labels, FAM and TAMRA, were compared when spermine
      was added under different experimental conditions. There was a marked difference
      upon conjugating the free dye to an oligonucleotide, when FAM was conjugated to
      an oligonucleotide there was around a six fold decrease in emission, compared to
      a six fold increase when TAMRA was conjugated to an oligonucleotide. Dye labelled
      single and double stranded DNA also behaved differently with double stranded DNA
      labelled with FAM being a much more efficient emitter in the mid pH range,
      however TAMRA becomes increasingly less efficient as the pH rises. Upon addition
      of the base spermine, signal enhancement from the FAM labelled oligonucleotide is
      observed. Increasing probe concentrations of TAMRA oligonucleotide above 0.5 MUM
      led to signal reduction most likely through quenching, either by an interaction
      with guanine, or through self-quenching. By using different bases for comparison,
      spermine and triethylamine (TEA), different affects were observed in the measured
      fluorescence signals. When TEA was added to FAM, a reduction in the pH dependence
      of fluorescence was observed, which may be useful for mid pH range assays. With
      the drive to increase information content and decrease time and complexity of DNA
      assays it is likely that more assays will be carried out in complex media such as
      extracted DNA fragments and PCR product. This model study indicates that dye DNA
      and dye spermine interactions are dye specific and that extreme care with
      conditions is necessary particularly if it is intended to determine the
      concentrations of multiple analytes using probes labelled with different dyes. 

PMID- 24915045
TI  - A synthetic sex ratio distortion system for the control of the human malaria
      mosquito.
AB  - It has been theorized that inducing extreme reproductive sex ratios could be a
      method to suppress or eliminate pest populations. Limited knowledge about the
      genetic makeup and mode of action of naturally occurring sex distorters and the
      prevalence of co-evolving suppressors has hampered their use for control. Here we
      generate a synthetic sex distortion system by exploiting the specificity of the
      homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene
      sequences of the malaria vector Anopheles gambiae that are located exclusively on
      the mosquito's X chromosome. We combine structure-based protein engineering and
      molecular genetics to restrict the activity of the potentially toxic endonuclease
      to spermatogenesis. Shredding of the paternal X chromosome prevents it from being
      transmitted to the next generation, resulting in fully fertile mosquito strains
      that produce >95% male offspring. We demonstrate that distorter male mosquitoes
      can efficiently suppress caged wild-type mosquito populations, providing the
      foundation for a new class of genetic vector control strategies. 

PMID- 24915046
TI  - "I do not want my baby to suffer as I did"; prenatal and preimplantation genetic
      diagnosis for BRCA1/2 mutations: a case report and genetic counseling
      considerations.
AB  - This article presents the complexity of prenatal genetic diagnosis and
      preimplantation genetic diagnosis for hereditary breast-ovarian cancer syndrome.
      These issues are discussed using a case report to highlight the genetic
      counseling process, together with decision-making considerations, in light of the
      clinical, psychological, and ethical perspectives, of both the mutation carriers
      and health professionals; and the health policy regarding these procedures in
      Israel compared to several European countries. 

PMID- 24915044
TI  - Metabolic disease risk in children by salivary biomarker analysis.
AB  - OBJECTIVE: The study of obesity-related metabolic syndrome or Type 2 diabetes
      (T2D) in children is particularly difficult because of fear of needles. We tested
      a non-invasive approach to study inflammatory parameters in an at-risk population
      of children to provide proof-of-principle for future investigations of vulnerable
      subjects. DESIGN AND METHODS: We evaluated metabolic differences in 744, 11-year
      old children selected from underweight, normal healthy weight, overweight and
      obese categories by analyzing fasting saliva samples for 20 biomarkers. Saliva
      supernatants were obtained following centrifugation and used for analyses.
      RESULTS: Salivary C-reactive protein (CRP) was 6 times higher, salivary insulin
      and leptin were 3 times higher, and adiponectin was 30% lower in obese children
      compared to healthy normal weight children (all P<0.0001). Categorical analysis
      suggested that there might be three types of obesity in children. Distinctly
      inflammatory characteristics appeared in 76% of obese children while in 13%,
      salivary insulin was high but not associated with inflammatory mediators. The
      remaining 11% of obese children had high insulin and reduced adiponectin. Forty
      percent of the non-obese children were found in groups which, based on biomarker
      characteristics, may be at risk for becoming obese. CONCLUSIONS: Significantly
      altered levels of salivary biomarkers in obese children from a high-risk
      population, suggest the potential for developing non-invasive screening
      procedures to identify T2D-vulnerable individuals and a means to test
      preventative strategies.

PMID- 24915047
TI  - Permeability study of ciprofloxacin from ultra-thin nanofibrous film through
      various mucosal membranes.
AB  - Permeability plays an important role to achieve the desired therapeutic outcomes.
      Present study was designed to investigate the permeability of ciprofloxacin from
      ultrathin polyvinyl alcohol nanofiber through different biological membranes.
      Results of the permeability studies indicated that nanofibers exhibit higher drug
      permeability than plane drug. Intestinal tissue shows maximum permeability
      followed by eye, trachea, sublingual, rectal, and skin. Permeability studies also
      inferred a steady-state release of drug of the nanofiber, whereas a high degree
      of fluctuations was observed in plane drug. Nanofiber being 2D nanoscale material
      provides numerous advantages to be used as an encapsulated carrier system to
      improve the therapeutic effectiveness. 

PMID- 24915049
TI  - 1,2-cis Alkyl glycosides: straightforward glycosylation from unprotected 1
      thioglycosyl donors.
AB  - A 1,2-cis-alkyl glycosidation protocol that makes use of unprotected phenyl 1
      thioglycosyl donors is reported. Glycosylation of various functionalized alcohols
      was accomplished in moderate to high yield and selectivity to give the 1,2-cis
      glycosides. In order to quickly develop optimum glycosylation conditions, an FIA
      (flow injection analysis)-ESI-TOF-MS method was developed that enabled rapid and
      quantitative evaluation of yield on small scale. This methodology, coupled with
      NMR spectroscopy, allowed for rapid evaluation of the overall reactions. 

PMID- 24915048
TI  - Phenotypic, antimicrobial susceptibility profile and virulence factors of
      Klebsiella pneumoniae isolated from buffalo and cow mastitic milk.
AB  - Studies on the prevalence and virulence genes of Klebsiella mastitis pathogens in
      a buffalo population are undocumented. Also, the association of rmpA kfu, uge,
      magA, Aerobactin, K1 and K2 virulent factors with K. pneumoniae buffalo, and cow
      mastitis is unreported. The virulence of K. pneumoniae was evaluated through both
      phenotypic and molecular assays. In vivo virulence was assessed by the Vero cell
      cytotoxicity, suckling mouse assay and mice lethality test. Antimicrobial
      susceptibility was tested by disk diffusion method. The 45 K. pneumoniae isolates
      from buffalo (n = 10/232) and cow (n = 35/293) milk were isolated (45/525; 8.6%)
      and screened via PCR for seven virulence genes encoding uridine diphosphate
      galactose 4 epimerase encoding gene responsible for capsule and smooth
      lipopolysaccharide synthesis (uge), siderophores (kfu and aerobactin),
      protectines or invasins (rmpA and magA), and the capsule and hypermucoviscosity
      (K1 and K2). The most common virulence genes were rmpA, kfu, uge, and magA (77.8%
      each). Aerobactin and K1 genes were found at medium rates of 66.7% each and K2
      (55.6%). The Vero cell cytotoxicity and LD (50) in mice were found in 100% of
      isolates. A multidrug resistance pattern was observed for 40% of the
      antimicrobials. The distribution of virulence profiles indicate a role of rmpA,
      kfu, uge, magA, Aerobactin, and K1 and K2 in pathogenicity of K. pneumoniae in
      udder infections and invasiveness, and constitutes a threat for vulnerable
      animals, even more if they are in combination with antibiotic resistance.

PMID- 24915050
TI  - Antiretroviral therapy for refugees and internally displaced persons: a call for
      equity.

PMID- 24915053
TI  - The construction of rigid supramolecular polymers in water through the self
      assembly of rod-like monomers and cucurbit[8]uril.
AB  - Two new types of supramolecular polymers have been constructed via the self
      assembly of rigid rod-like monomers and cucurbit[8]uril (CB[8]) in water. These
      supramolecular polymers possessed rigid backbones and further aggregated into
      stick-like bunched fibres. 

PMID- 24915051
TI  - Activation of liver X receptor improves viability of adipose-derived mesenchymal
      stem cells to attenuate myocardial ischemia injury through TLR4/NF-kappaB and
      Keap-1/Nrf-2 signaling pathways.
AB  - AIMS: Clinical application of cellular therapy for cardiac regeneration is
      significantly hampered by the low retention of engrafted cells, mainly
      attributable to the poor microenvironment dominated by inflammation and oxidative
      stress in the host's infarcted myocardium. This study aims at investigating
      whether liver X receptor (LXR) agonist T0901317 will improve survival of adipose
      derived mesenchymal stem cells (AD-MSCs) after transplantation into infarcted
      hearts. RESULTS: Noninvasive in vivo bioluminescence imaging and histological
      staining showed that LXR agonist T0901317 improved the retention and survival of
      intramyocardially injected AD-MSCs. Moreover, combined therapy of LXR agonist and
      AD-MSCs inhibited host cardiomyocyte apoptosis, reduced fibrosis, and improved
      cardiac function, while it concomitantly decreased inflammatory cytokines (e.g.,
      tumor necrosis factor-alpha and interleukin-6) and increased growth factor (e.g.,
      vascular endothelial growth factor and basic fibroblast growth factor) expression
      in infarct myocardium. To reveal possible mechanisms, AD-MSCs were subjected to
      hypoxia/serum deprivation (H/SD) injury to simulate ischemic conditions in vivo.
      The LXR agonist (10(-7) mM) improved AD-MSC survival under H/SD condition.
      Western blot revealed that the LXR agonist reduced TLR4, TRAF-6, and MyD88
      protein expression, inhibited IkappaBalpha phosphorylation and NF-kappaB-p65
      nuclear translocation, which resulted in accelerated Keap-1 protein degradation,
      enhanced Nrf-2 nuclear translocation, and increased HO-1 protein expression.
      INNOVATION AND CONCLUSION: LXR agonist can enhance the functional survival of
      transplanted AD-MSCs in infarcted myocardium, at least partially, via modulation
      of the TLR4/NF-kappaB and Keap-1/Nrf-2 signaling pathways. Moreover, combined
      therapy of LXR agonist and AD-MSCs has a synergetic effect on cardiac repair and
      functional improvement after infarction.

PMID- 24915052
TI  - Randomized trial comparing the effects of a low-dose combination of nifedipine
      GITS and valsartan versus high-dose monotherapy on central hemodynamics in
      patients with inadequately controlled hypertension: FOCUS study.
AB  - OBJECTIVES: Measurement of central blood pressure provides prognostic information
      beyond conventional peripheral blood pressure (BP). However, few studies have
      directly compared the effects of antihypertensives on central hemodynamics. This
      study investigated the effects of a low-dose combination of nifedipine
      Gastrointestinal Therapeutic System (GITS) and valsartan versus high-dose
      monotherapy with either agent in reducing central BP in essential hypertension
      inadequately controlled by low-dose monotherapy. MATERIALS AND METHODS: In this
      prospective, open-label, randomized, active-controlled, multicenter 8-week study,
      patients not meeting the target BP after 4 weeks of treatment with low-dose
      monotherapy were randomized to receive nifedipine GITS 30 mg plus valsartan 80 mg
      (N30+V80), nifedipine GITS 60 mg (N60), or valsartan 160 mg (V160) for a further
      4 weeks. Central hemodynamics were measured by applanation tonometry. RESULTS: A
      total of 391 patients were enrolled. Reduction in central systolic BP from
      baseline to week 8, the primary efficacy variable, was significantly greater in
      the N30+V80 group (-27.2+/-14.7 mmHg) and the N60 group (-27.1+/-16.5 mmHg)
      compared with V160 group (-14.4+/-16.6 mmHg). Decrease in the augmentation index
      in the N60 group was significantly greater compared with V160 alone, without
      differences between combination therapy and either high-dose monotherapy.
      Decreases in brachial systolic BP were significantly greater in the N30+V80 and
      N60 groups than in the V160 group. By multiple regression analysis, most
      differences in drug effects on central hemodynamics disappeared after controlling
      for changes in peripheral BP. A low rate of adverse events occurred in all
      treatment groups. CONCLUSION: A low-dose combination of nifedipine GITS plus
      valsartan or high-dose nifedipine was more effective in improving central
      hemodynamics than high-dose valsartan in patients with hypertension, mostly
      because of the improvement in peripheral (brachial) hemodynamics.

PMID- 24915054
TI  - Single-sheeted double many-body expansion potential energy surface for ground
      state ClO2.
AB  - A global single-sheeted double many-body expansion potential energy surface is
      reported for the ground electronic state of ClO2. The potential energy surface is
      obtained by fitting 3200 energy points that map all atom-diatom dissociation
      channels as well as all relevant stationary points, including the well-known OClO
      and ClOO structures. The ab initio calculations are obtained at the
      multireference configuration interaction level of theory, employing the cc-pVXZ
      (X = D, T) Dunning basis sets, and then extrapolated to the complete basis set
      limit with the generalized uniform singlet- and triplet-pair protocol. The
      topographical features of the novel global potential energy surface are examined
      in detail. 

PMID- 24915055
TI  - The distribution of the cortical origin of the corticoreticular pathway in the
      human brain: a diffusion tensor imaging study.
AB  - We investigated the distribution of the cortical origin of the corticoreticular
      pathway (CRP) in the human brain. Forty normal subjects were recruited and CRPs
      from four cortical areas were reconstructed. The first cortical origin area of
      the CRP was the premotor cortex and the next was the primary motor cortex.
      Although the CRP fibers also originated from the primary somatosensory cortex and
      prefrontal cortex, they occupied the smallest portion among four regions of
      interest.

PMID- 24915057
TI  - Experimental observation of negative capacitance in ferroelectrics at room
      temperature.
AB  - Effective negative capacitance has been postulated in ferroelectrics because
      there is a hysteresis in plots of polarization-electric field. Compelling
      experimental evidence of effective negative capacitance is presented here at room
      temperature in engineered devices, where it is stabilized by the presence of a
      paraelectric material. In future integrated circuits, the incorporation of such
      negative capacitance into MOSFET gate stacks would reduce the subthreshold slope,
      enabling low power operation and reduced self-heating.

PMID- 24915056
TI  - Phase-dependent modulation of corticospinal excitability during the observation
      of the initial phase of gait.
AB  - This study was undertaken to identify the temporal characteristics of
      corticospinal excitability of tibialis anterior muscle during the observation of
      the initial phase of gait. For this purpose, using transcranial magnetic
      stimulation, we recorded motor evoked potentials (MEPs) during the observation of
      the second step of an actor's first three steps of gait initiation with (complex
      gait) or without (normal gait) an obstacle and unstable surface. The results
      demonstrate that (1) MEPs during the observation of the initial phase of normal
      gait were significantly increased only at early swing phase, but not other phases
      (mid-swing, heel contact, mid-stance, and heel off) and (2) MEPs during the
      observation of the initial phase of complex gait were significantly increased at
      early swing and also at mid-swing and heel contact phases. These findings provide
      the first evidence that corticospinal excitability during the observation of
      gait, especially the initial phase, is modulated in phase- and motor-demanded
      dependent manners.

PMID- 24915058
TI  - Interplay between anthocyanins and gut microbiota.
AB  - Anthocyanins are naturally occurring compounds abundant in the human diet.
      Evidence has accumulated regarding the positive association of their intake with
      healthy biological effects. The microbiota has just been started to be considered
      as a metabolic organ, hence contributing to the metabolism of phenolic compounds
      and, consequently, to their bioavailability and the biological effects displayed
      by them. This review aimed to compile information regarding interaction of
      anthocyanins with the microbiota, from two perspectives: (i) identification of
      their colonic metabolites as potential bioactive molecules and (ii) their role as
      prebiotic agents. These perspectives are key points in anthocyanin metabolomics.
      Several metabolites have been identified after anthocyanin consumption with
      potential health benefits, in particular phenolic acids and simple phenols. On
      the other hand, microbiota modulation is closely related to several physiological
      impairments, and its modulation has been considered as a possible mechanism by
      which phenolic compounds may exert their effect. 

PMID- 24915059
TI  - Conformational analysis, molecular structure and solid state simulation of the
      antiviral drug acyclovir (zovirax) using density functional theory methods.
AB  - The five tautomers of the drug acyclovir (ACV) were determined and optimised at
      the MP2 and B3LYP quantum chemical levels of theory. The stability of the
      tautomers was correlated with different parameters. On the most stable tautomer
      N1 was carried out a comprehensive conformational analysis, and the whole
      conformational parameters (R, beta, Phi, phi1, phi2, phi3, phi4, phi5) were
      studied as well as the NBO Natural atomic charges. The calculations were carried
      out with full relaxation of all geometrical parameters. The search located at
      least 78 stable structures within 8.5 kcal/mol electronic energy range of the
      global minimum, and classified in two groups according to the positive or
      negative value of the torsional angle j1. In the nitrogen atoms and in the O2'
      and O5' oxygen atoms of the most stable conformer appear a higher reactivity than
      in the natural nucleoside deoxyguanosine. The solid state was simulated through a
      dimer and tetramer forms and the structural parameters were compared with the X
      ray crystal data available. Several general conclusions were emphasized. 

PMID- 24915060
TI  - The acquisition of relative clauses in spontaneous child speech in Mandarin
      Chinese - ERRATUM.

PMID- 24915061
TI  - Effects of contralateral noise on the 20-Hz auditory steady state response-
      magnetoencephalography study.
AB  - The auditory steady state response (ASSR) is an oscillatory brain response, which
      is phase locked to the rhythm of an auditory stimulus. ASSRs have been recorded
      in response to a wide frequency range of modulation and/or repetition, but the
      physiological features of the ASSRs are somewhat different depending on the
      modulation frequency. Recently, the 20-Hz ASSR has been emphasized in clinical
      examinations, especially in the area of psychiatry. However, little is known
      about the physiological properties of the 20-Hz ASSR, compared to those of the 40
      Hz and 80-Hz ASSRs. The effects of contralateral noise on the ASSR are known to
      depend on the modulation frequency to evoke ASSR. However, the effects of
      contralateral noise on the 20-Hz ASSR are not known. Here we assessed the effects
      of contralateral white noise at a level of 70 dB SPL on the 20-Hz and 40-Hz ASSRs
      using a helmet-shaped magnetoencephalography system in 9 healthy volunteers (8
      males and 1 female, mean age 31.2 years). The ASSRs were elicited by monaural
      1000-Hz 5-s tone bursts amplitude-modulated at 20 and 39 Hz and presented at 80
      dB SPL. Contralateral noise caused significant suppression of both the 20-Hz and
      40-Hz ASSRs, although suppression was significantly smaller for the 20-Hz ASSRs
      than the 40-Hz ASSRs. Moreover, the greatest suppression of both 20-Hz and 40-Hz
      ASSRs occurred in the right hemisphere when stimuli were presented to the right
      ear with contralateral noise. The present study newly showed that 20-Hz ASSRs are
      suppressed by contralateral noise, which may be important both for
      characterization of the 20-Hz ASSR and for interpretation in clinical situations.
      Physicians must be aware that the 20-Hz ASSR is significantly suppressed by sound
      (e.g. masking noise or binaural stimulation) applied to the contralateral ear. 

PMID- 24915062
TI  - Hydrogel micropattern-incorporated fibrous scaffolds capable of sequential growth
      factor delivery for enhanced osteogenesis of hMSCs.
AB  - In this study, we developed multi-functional biomimetic tissue engineered
      scaffolds that are capable of controlling the spatial locations of stem cells and
      releasing multiple growth factors with a controlled dose and rate of delivery.
      This novel scaffold was fabricated by combining electrospinning and
      photolithography and consisted of polycaprolactone (PCL)/gelatin fibers and
      poly(ethylene glycol) (PEG) hydrogel micropatterns. The utility of this system
      was investigated in the context of the osteogenesis of human mesenchymal stem
      cells (hMSCs). When hMSCs were seeded onto hydrogel-incorporated fibrous
      scaffolds, they selectively adhered and grew only in the fiber region due to the
      non-adhesiveness of the PEG hydrogel, enabling spatial positioning of hMSCs on a
      micrometer scale. For osteogenic differentiation of hMSCs, basic fibroblast
      growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) were loaded on the
      fibers and within the hydrogel matrix, respectively, to enable sequential
      delivery of low doses of bFGF during the early stages and sustained release of
      BMP-2 for long periods. According to in vitro studies, hMSCs cultured on the
      scaffolds capable of sequential delivery of bFGF and BMP-2 showed stronger
      osteogenic commitment in culture than those on scaffolds without any growth
      factors or scaffolds with single administration of either bFGF or BMP-2 under the
      same conditions. The results demonstrate that hydrogel-incorporated fibrous
      scaffolds can provide not only biomimetic structures with micropatterned
      nanostructures but also a suitable biochemical environment with controlled
      release of multiple growth factors, which may eventually facilitate the control
      of stem cell fates for various regenerative therapies. 

PMID- 24915063
TI  - The Evonik-Mainz-Eye-Care-Study (EMECS): design and execution of the screening
      investigation.
AB  - PURPOSE: To determine if screening for major ophthalmological diseases is
      feasible within the frame of routine occupational medicine examinations in a
      large working population. METHODS: 13037 employees of Evonik Industries aged 40
      to 65 years were invited to be screened for major ophthalmological diseases
      (glaucoma, age related macular degeneration and diabetic retinopathy between June
      2007 and March 2008 within an extended setting of occupational medicine.
      Ophthalmological examinations consisted of visual acuity, objective refraction,
      pachymetry, tonometry, perimetry (frequency doubling technology), confocal
      scanning laser ophthalmoscopy and digital fundus photography. Participants
      responded to a questionnaire addressing history of ocular and general diseases
      and social history. RESULTS: 4183 participants (961 female and 3222 male) were
      examined at 13 different sites. Response rates for eligible persons at those
      sites ranged from 17.9 to 60.5% but were in part limited by availability of
      examination slots. Average age of participants was 48.4 +/- 5.4 years (mean +/-
      SD). 4147 out of 4183 subjects (99.1%) had a visual acuity >= 0.5 in the better
      eye and 3665 out of 4183 (87.6%) subjects had a visual acuity >= 0.8 in the
      better eye. 1629 participants (38.9%) had previously not been seen by an
      ophthalmologist at all or not within the last three years. CONCLUSION: This
      article describes the study design and basic characteristics of study
      participants within a large occupational medicine based screening study for
      ophthalmological diseases. Response rates exceeded expectations and were limiting
      examination capacity. Meaningful data could be obtained for almost all
      participants. We reached participants who previously had not received ophthalmic
      care. Thus, ophthalmological screening appears to be feasible within the frame of
      routine occupational medicine examinations.

PMID- 24915065
TI  - Metastasis, risk factors and prognostic significance of splenic hilar lymph nodes
      in gastric adenocarcinoma.
AB  - BACKGROUND: The metastatic rate and risk factors of splenic hilar (No.10) lymph
      nodes (LNs) in gastric adenocarcinoma were still variable and uncertain, and the
      prognostic significance of No.10 LNs was also controversial. The aim of this
      retrospective study was to analyze the metastatic rate, risk factors and
      prognostic significance of No.10 LNs in gastric adenocarcinoma. METHODS: From
      August 2007 to December 2011, 205 patients who were diagnosed with primary
      gastric adenocarcinoma and underwent total or proximal gastrectomy plus No.10 LNs
      dissection in West China Hospital were enrolled. Clinicopathological features and
      survival outcomes were retrospectively analyzed. RESULTS: Mean numbers of
      harvested LNs and metastatic LNs were 34.8+/-12.6 (15-73) and 8.7+/-10.8 (0-67),
      respectively. The proportion of cases with positive No.10 LNs was 8.8% (18/205).
      In all 204 dissected No.10 LNs, 47 LNs (23.0%) were metastatic. In 52.2%
      (107/205) patients, the dissected splenic hilar tissues were histologically
      determined as only fat tissues but without LNs structure. Histological evidence
      of LNs structure was found in 98 (47.8%) patients with 18.4% (18/98) metastatic
      No.10 LNs. In multivariate logistic regression analysis, metastasis of No.10 LNs
      was significantly correlated with No.4sa LNs (p = 0.010) and pN stage (p =
      0.012). Regarding survival analysis, 199 (97.1%) patients were followed up (0.6
      74.8 months). In all patients with R0 resection, metastatic No.10 LNs caused
      significantly worse prognosis both in Kaplan-Meier (p = 0.006) and Cox regression
      analysis (p = 0.031). CONCLUSIONS: Although the metastatic rate of No.10 LNs was
      8.8%, dissection of No.10 LNs might be meaningful due to the poor prognosis of
      positive cases. And attentions should be also paid to its correlated factors
      including pN stage and No.4sa LNs.

PMID- 24915064
TI  - Hepatitis B and Delta virus are prevalent but often subclinical co-infections
      among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional
      study.
AB  - BACKGROUND: Co-infection with human immunodeficiency virus (HIV) and hepatitis B
      virus (HBV) may lead to accelerated hepatic disease progression with higher rates
      of liver cirrhosis and liver-related mortality compared with HBV mono-infection.
      Co or super-infection with hepatitis Delta virus (HDV) may worsen the liver
      disease and complicate treatment possibilities. METHODS: In this cross-sectional
      study we included HIV-infected individuals who had a routine blood analysis
      performed at an HIV clinic in Bissau, Guinea-Bissau between the 28th of April and
      30th of September 2011. All patients were interviewed, had a clinical exam
      performed and had a blood sample stored. The patients' samples were tested for
      HBV and HDV serology, and HBV/HDV viral loads were analyzed using in-house real
      time PCR methods. RESULTS: In total, 576 patients (417 HIV-1, 104 HIV-2 and 55
      HIV-1/2) were included in this study. Ninety-four (16.3%) patients were HBsAg
      positive of whom 16 (17.0%) were HBeAg positive. In multivariable logistic
      regression analysis, CD4 cell count <200 cells/ul and animist religion were
      significantly associated with HBsAg positivity. Due to scarcity of available
      plasma, virological analyses were not performed for eight patients. HBV DNA was
      detected in 42 of 86 samples (48.8%) positive for HBsAg and genotyping was
      performed in 26 patients; 25 of whom had genotype E and one genotype D. Among 9
      patients on antiretroviral treatment (ART), one patient had the [L180M, M204V]
      mutation associated with lamivudine resistance. Among the HBsAg positive patients
      25.0% were also positive for anti-HDV and 4/9 (44.4%) had detectable HDV RNA.
      CONCLUSION: HBV and HDV were frequent co-infections among HIV positive patients
      in Guinea-Bissau and chronic infection was associated with severe
      immunosuppression. Lamivudine was widely used among HBsAg positive patients with
      the risk of developing resistant HBV.

PMID- 24915066
TI  - Effects of long-term acupuncture treatment on resting-state brain activity in
      migraine patients: a randomized controlled trial on active acupoints and inactive
      acupoints.
AB  - BACKGROUND: Acupuncture has been commonly used for preventing migraine attacks
      and relieving pain during a migraine, although there is limited knowledge on the
      physiological mechanism behind this method. The objectives of this study were to
      compare the differences in brain activities evoked by active acupoints and
      inactive acupoints and to investigate the possible correlation between clinical
      variables and brain responses. METHODS AND RESULTS: A randomized controlled trial
      and resting-state functional magnetic resonance imaging (fMRI) were conducted. A
      total of eighty migraineurs without aura were enrolled to receive either active
      acupoint acupuncture or inactive acupoint acupuncture treatment for 8 weeks, and
      twenty patients in each group were randomly selected for the fMRI scan at the end
      of baseline and at the end of treatment. The neuroimaging data indicated that
      long-term active acupoint therapy elicited a more extensive and remarkable
      cerebral response compared with acupuncture at inactive acupoints. Most of the
      regions were involved in the pain matrix, lateral pain system, medial pain
      system, default mode network, and cognitive components of pain processing.
      Correlation analysis showed that the decrease in the visual analogue scale (VAS)
      was significantly related to the increased average Regional homogeneity (ReHo)
      values in the anterior cingulate cortex in the two groups. Moreover, the decrease
      in the VAS was associated with increased average ReHo values in the insula which
      could be detected in the active acupoint group. CONCLUSIONS: Long-term active
      acupoint therapy and inactive acupoint therapy have different brain activities.
      We postulate that acupuncture at the active acupoint might have the potential
      effect of regulating some disease-affected key regions and the pain circuitry for
      migraine, and promote establishing psychophysical pain homeostasis. TRIAL
      REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-13003635.

PMID- 24915067
TI  - Comparative genomics and association mapping approaches for blast resistant genes
      in finger millet using SSRs.
AB  - The major limiting factor for production and productivity of finger millet crop
      is blast disease caused by Magnaporthe grisea. Since, the genome sequence
      information available in finger millet crop is scarce, comparative genomics plays
      a very important role in identification of genes/QTLs linked to the blast
      resistance genes using SSR markers. In the present study, a total of 58 genic
      SSRs were developed for use in genetic analysis of a global collection of 190
      finger millet genotypes. The 58 SSRs yielded ninety five scorable alleles and the
      polymorphism information content varied from 0.186 to 0.677 at an average of
      0.385. The gene diversity was in the range of 0.208 to 0.726 with an average of
      0.487. Association mapping for blast resistance was done using 104 SSR markers
      which identified four QTLs for finger blast and one QTL for neck blast
      resistance. The genomic marker RM262 and genic marker FMBLEST32 were linked to
      finger blast disease at a P value of 0.007 and explained phenotypic variance (R2)
      of 10% and 8% respectively. The genomic marker UGEP81 was associated to finger
      blast at a P value of 0.009 and explained 7.5% of R2. The QTLs for neck blast was
      associated with the genomic SSR marker UGEP18 at a P value of 0.01, which
      explained 11% of R2. Three QTLs for blast resistance were found common by using
      both GLM and MLM approaches. The resistant alleles were found to be present
      mostly in the exotic genotypes. Among the genotypes of NW Himalayan region of
      India, VHC3997, VHC3996 and VHC3930 were found highly resistant, which may be
      effectively used as parents for developing blast resistant cultivars in the NW
      Himalayan region of India. The markers linked to the QTLs for blast resistance in
      the present study can be further used for cloning of the full length gene, fine
      mapping and their further use in the marker assisted breeding programmes for
      introgression of blast resistant alleles into locally adapted cultivars.

PMID- 24915068
TI  - Arterial and venous aneurysms associated with arteriovenous malformations.
AB  - OBJECTIVE: To identify prioritization based on hemorrhagic risk and indications
      for treatment of arterial and venous aneurysms associated with arteriovenous
      malformation (AVM). METHODS: From a global series of 400 consecutively treated
      AVMs, 34 patients (8.5%) with 45 arterial or venous aneurysms were extrapolated.
      These 45 lesions were classified as unrelated aneurysms (n = 5 cases; 11.%), flow
      related aneurysms (n = 18 cases; 40%), and intranidal and postnidal venous
      aneurysms (n = 22; 49.%). The 18 flow-related aneurysms were further divided into
      remote (n = 6 cases) and adjacent (n = 12 cases) types. Of 45 aneurysms
      associated with AVMs, 15 were unruptured with a 5-year mean follow-up. Various
      possible risk indicators were considered and measured by univariate and
      multivariate analyses. RESULTS: During the follow-up period, 1 of 15 unruptured
      aneurysms bled, and the patient died. A significantly different bleeding
      incidence was found between unrelated aneurysm and flow-related aneurysm types (P
      = 0.002). Bleeding was significantly less probable in flow-related remote
      aneurysm type than in venous and flow-related adjacent aneurysm types (P =
      0.007). The location of the aneurysm was the only true risk factor for bleeding;
      the other parameters had no influence on bleeding. CONCLUSIONS: In this series,
      different subtypes of aneurysms associated with AVMs had different clinical
      behaviors. The bleeding risk of the unrelated aneurysm and the flow-related
      remote aneurysm types should be considered almost the same as any other
      unruptured aneurysm. In other words, bleeding risk should be considered taking
      into account the parameters established by the International Study of Unruptured
      Intracranial Aneurysms (location, size, and morphology). Conversely, flow-related
      adjacent aneurysm and venous aneurysm types have significantly higher bleeding
      potentials.

PMID- 24915069
TI  - Pituitary apoplexy: large surgical series with grading system.
AB  - BACKGROUND: Pituitary apoplexy is an infrequent occurrence that can require
      timely treatment. The term "pituitary apoplexy" as used in the literature
      describes a heterogeneous spectrum. There is controversy about which subsets
      require urgent as opposed to elective surgical treatment or even medical
      treatment alone. We present a retrospective series of 109 consecutive cases of
      pituitary apoplexy from a single institution from 1992-2012 and develop a
      comprehensive classification system to analyze outcome. METHODS: Surgical and
      endocrine consult databases were reviewed to analyze patterns of presentation,
      imaging, treatment, and outcomes. RESULTS: Most of the patients in this series
      presented clinically with "classic" pituitary apoplexy (97%), had magnetic
      resonance imaging for evaluation (99%), underwent transsphenoidal surgery as
      their primary treatment (93%), and were found to have pituitary adenomas on
      histopathology (90%). We categorized patients into 5 grades based on clinical
      presentation. Tumor volume, cavernous sinus involvement, suprasellar extension,
      and need for ongoing endocrine replacement correlated with grade. Long-term
      endocrine replacement at follow-up was required in 62%-68% of patients with a
      higher grade compared with 0-23% of patients with a lower grade. Higher grade
      patients tended to undergo earlier surgery after symptom onset. Symptoms resolved
      or improved with treatment in 92%-100% of patients across all grades with good
      general outcomes for visual deficits and ocular motility problems, validating
      management decisions overall. CONCLUSIONS: We offer a simple yet comprehensive
      grading system to classify the clinical spectrum of pituitary apoplexy, which has
      implications for management, outcomes, and categorization for future studies.

PMID- 24915070
TI  - Combined use of a gasket seal closure and a vascularized pedicle nasoseptal flap
      multilayered reconstruction technique for high-flow cerebrospinal fluid leaks
      after endonasal endoscopic skull base surgery.
AB  - OBJECTIVE: To assess the efficacy of the combined use of a gasket seal closure
      and a vascularized pedicle nasoseptal flap (VP-NSF) multilayered reconstruction
      technique for high-flow cerebrospinal fluid (CSF) leaks resulting from endonasal
      endoscopic skull base surgery. METHODS: From October 2009-June 2011, a VP-NSF
      multilayered reconstruction technique was used (single technique group) for
      patients with intraoperative high-flow CSF leaks; from July 2011-February 2013, a
      combination of a gasket seal closure and a VP-NSF multilayered reconstruction
      technique was used (combined technique group). A lumbar drain was placed after
      the operation. The rates of postoperative CSF leaks and repair-related
      complications in the 2 groups were analyzed. RESULTS: The single technique group
      comprised 18 patients with a mean follow-up of 31.7 months; there were 5
      postoperative CSF leaks (27.7%). The combined technique group comprised 15
      patients with a mean follow-up of 13.6 months; no CSF leaks occurred (P < 0.05).
      The rate of intracranial infection in the single technique group was
      significantly higher than in the combined technique group. CONCLUSIONS: The
      combined use of a gasket seal closure and a VP-NSF multilayered reconstruction
      technique for high-flow CSF leaks after endonasal endoscopic skull base surgery
      may significantly reduce the rates of postoperative CSF leaks and intracranial
      infections. Lumbar drainage after the operation is a necessary auxiliary method.

PMID- 24915071
TI  - Aberrant venous drainage pattern in a medial sphenoid wing dural arteriovenous
      fistula: commentary.

PMID- 24915072
TI  - Non-ergot dopamine agonist rotigotine as a promising therapeutic tool in atypical
      parkinsonism syndromes: a 24 months pilot observational open-label study.
AB  - Rotigotine (RTG) is a non-ergot dopamine agonist developed as a new transdermal
      formulation, indicated for use in early and advanced Parkinson's disease (PD).
      The potential advantages of the RTG patch include immediacy of effect onset,
      constant drug delivery, better tolerability avoiding drug peaks and easy of use,
      helping patient's compliance. So, RTG patch appears to be a suitable candidate in
      the treatment of patients with atypical parkinsonism. The present is an
      observational study to evaluate the efficacy and tolerability of RTG in patients
      affected by atypical parkinsonian disorders. 61 subjects with diagnosis of
      atypical parkinsonian disorders were treated with transdermal RTG. Diagnosis was:
      Parkinson disease with dementia, multiple system atrophy parkinsonian type,
      multiple system atrophy cerebellar type, progressive sopranuclear palsy, cortico
      basal degeneration, Lewy body dementia and fronto-temporal dementia with
      parkinsonism. Patients were evaluated by UPDRS-III, NPI, MMSE and adverse events
      (AEs) were recorded. Patients treated with RTG show an overall decrease of UPDRS
      III scores without increasing behavioral disturbances. Main adverse events (AE)
      were hypotension (14 patients), nausea (13), vomiting (5), drowsiness (5),
      tachycardia (2) dystonia (3 patients, all treated with concomitant l-dopa). On
      the whole, 16 patients were affected by AE and 7 patients suspended RTG treatment
      due to AE (vomiting, tachycardia and sleepiness). In our population transdermal
      RTG seems to be effective and well tolerated. Due to its system of drug delivery,
      RTG appears to be a suitable therapy in elderly patients as it has a good
      tolerability profile, improves patient's compliance and helps management of
      fragile patients. 

PMID- 24915073
TI  - Prevalence and predictors of polypharmacy among Korean elderly.
AB  - OBJECTIVE: Polypharmacy is widespread in the elderly because of their multiple
      chronic health problems. The objective of this study was to investigate the
      prevalence and predictors associated with polypharmacy in a nationally
      representative sample of Korean elderly individuals. METHODS: We used the Korea
      Health Insurance Review and Assessment Service - National Patient Sample (HIRA
      NPS) data from 2010 and 2011. We used information on 319,185 elderly patients
      (aged 65 years or older) between January 1, 2010 and December 31, 2011 from the
      HIRA-NPS database. We defined 'polypharmacy' as the concurrent use of 6
      medications or more per person, 'major polypharmacy' as 11 medications or more,
      and 'excessive polypharmacy' as 21 medications or more. The frequency and
      proportion (%) and their 95% confidence intervals were presented according to the
      polypharmacy definition. Polypharmacy was visualized by the Quantum Geographic
      Information Systems (QGIS) program to describe regional differences in patterns
      of drug use. Multivariate ordinal logistic regression was performed to estimate
      odds ratios (ORs) and their 95% confidence intervals (CI) to investigate the risk
      factors for polypharmacy. RESULTS: Of the Korean elderly studied, 86.4% had
      polypharmacy, 44.9% had major polypharmacy and 3.0% had excessive polypharmacy.
      Polypharmacy was found to be primarily concentrated in the Southwest region of
      the country. Significant associations between polypharmacy and the lower-income
      Medical Aid population (OR = 1.52, 95% CI 1.47, 1.56) compared with National
      Health Insurance patients was observed. CONCLUSIONS: Nationwide efforts are
      needed for managing polypharmacy among Korean elderly patients. In particular, a
      national campaign and education to promote appropriate use of medicines for the
      Medical Aid population is needed.

PMID- 24915074
TI  - Automation in biological crystallization.
AB  - Crystallization remains the bottleneck in the crystallographic process leading
      from a gene to a three-dimensional model of the encoded protein or RNA.
      Automation of the individual steps of a crystallization experiment, from the
      preparation of crystallization cocktails for initial or optimization screens to
      the imaging of the experiments, has been the response to address this issue.
      Today, large high-throughput crystallization facilities, many of them open to the
      general user community, are capable of setting up thousands of crystallization
      trials per day. It is thus possible to test multiple constructs of each target
      for their ability to form crystals on a production-line basis. This has improved
      success rates and made crystallization much more convenient. High-throughput
      crystallization, however, cannot relieve users of the task of producing samples
      of high quality. Moreover, the time gained from eliminating manual preparations
      must now be invested in the careful evaluation of the increased number of
      experiments. The latter requires a sophisticated data and laboratory information
      management system. A review of the current state of automation at the individual
      steps of crystallization with specific attention to the automation of
      optimization is given. 

PMID- 24915075
TI  - Structure of a His170Tyr mutant of thermostable pNPPase from Geobacillus
      stearothermophilus.
AB  - Using directed evolution based on random mutagenesis and heat-treated selection,
      a thermostable His170Tyr mutant of Geobacillus stearothermophilus thermostable p
      nitrophenylphosphatase (TpNPPase) was obtained. The temperature at which the
      His170Tyr mutant lost 50% of its activity (T1/2) was found to be 4.40 K higher
      than that of wild-type TpNPPase, and the melting temperature of the His170Tyr
      mutant increased by 2.39 K. The crystal structure of the His170Tyr mutant was
      then determined at 2.0 A resolution in the presence of a sodium ion and a sulfate
      ion in the active site. The cap domain of chain B shows a half-closed
      conformation. The hydrophobic side chain of the mutated residue, the
      hydroxyphenyl group, forms a hydrophobic contact with the methyl group of Ala166.
      This hydrophobic interaction was found using the Protein Interactions Calculator
      (PIC) web server with an interaction distance of 4.6 A, and might be a key factor
      in the thermostabilization of the His170Tyr mutant. This study potentially offers
      a molecular basis for both investigation of the catalytic mechanism and
      thermostable protein engineering. 

PMID- 24915076
TI  - GlmU (N-acetylglucosamine-1-phosphate uridyltransferase) bound to three magnesium
      ions and ATP at the active site.
AB  - N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU), a bifunctional enzyme
      exclusive to prokaryotes, belongs to the family of sugar nucleotidyltransferases
      (SNTs). The enzyme binds GlcNAc-1-P and UTP, and catalyzes a uridyltransfer
      reaction to synthesize UDP-GlcNAc, an important precursor for cell-wall
      biosynthesis. As many SNTs are known to utilize a broad range of substrates,
      substrate specificity in GlmU was probed using biochemical and structural
      studies. The enzymatic assays reported here demonstrate that GlmU is specific for
      its natural substrates UTP and GlcNAc-1-P. The crystal structure of GlmU bound to
      ATP and GlcNAc-1-P provides molecular details for the inability of the enzyme to
      utilize ATP for the nucleotidyltransfer reaction. ATP binding results in an
      inactive pre-catalytic enzyme-substrate complex, where it adopts an unusual
      conformation such that the reaction cannot be catalyzed; here, ATP is shown to be
      bound together with three Mg2+ ions. Overall, this structure represents the
      binding of an inhibitory molecule at the active site and can potentially be used
      to develop new inhibitors of the enzyme. Further, similar to DNA/RNA polymerases,
      GlmU was recently recognized to utilize two metal ions, MgA2+ and MgB2+, to
      catalyze the uridyltransfer reaction. Interestingly, displacement of MgB2+ from
      its usual catalytically competent position, as noted in the crystal structure of
      RNA polymerase in an inactive state, was considered to be a key factor inhibiting
      the reaction. Surprisingly, in the current structure of GlmU MgB2+ is similarly
      displaced; this raises the possibility that an analogous inhibitory mechanism may
      be operative in GlmU.

PMID- 24915077
TI  - Structures and binding specificity of galactose- and mannose-binding lectins from
      champedak: differences from jackfruit lectins.
AB  - Galactose-binding and mannose-binding lectins from the champedak fruit, which is
      native to South-east Asia, exhibit useful potential clinical applications. The
      specificity of the two lectins for their respective ligands allows the detection
      of potential cancer biomarkers and monitoring of the glycosylated state of
      proteins in human serum and/or urine. To fully understand and expand the use of
      these natural proteins, their complete sequences and crystal structures are
      presented here, together with details of sugar binding. 

PMID- 24915079
TI  - Structure of transportin SR2, a karyopherin involved in human disease, in complex
      with Ran.
AB  - Transportin SR2 (TRN-SR2) is a beta-type karyopherin responsible for the nuclear
      import of specific cargoes, including serine/arginine-rich splicing factors. The
      protein has been implicated in a variety of human diseases, including HIV
      infection, primary biliary cirrhosis and limb-girdle muscular dystrophy 1F.
      Towards understanding its molecular mechanism, a 2.9 A resolution crystal
      structure of human TRN-SR2 complexed with the small GTPase Ran has been
      determined. TRN-SR2 is composed of 20 alpha-helical HEAT repeats forming a
      solenoid-like fold. The first nine repeats form a 'cradle' for the binding of
      RanGTP, revealing similarities but also differences with respect to the related
      importin 13 complex. 

PMID- 24915080
TI  - Expression, purification and crystallization of a fungal type III polyketide
      synthase that produces the csypyrones.
AB  - CsyB from Aspergillus oryzae is a novel type III polyketide synthase that
      catalyzes the formation of csypyrone B1 [4-(3-acetyl-4-hydroxy-2-oxo-2H-pyran-6
      yl)butyric acid] from fatty acyl-CoA, malonyl-CoA and acetoacetyl-CoA.
      Recombinant CsyB expressed in Escherichia coli was crystallized by the sitting
      drop vapour-diffusion method. The crystals belonged to space P21, with unit-cell
      parameters a=70.0, b=104.8, c=73.5 A, beta=114.4 degrees .

PMID- 24915078
TI  - High-resolution crystal structures of two crystal forms of human cyclophilin D in
      complex with PEG 400 molecules.
AB  - Cyclophilin D (CypD) is a key mitochondrial target for amyloid-beta-induced
      mitochondrial and synaptic dysfunction and is considered a potential drug target
      for Alzheimer's disease. The high-resolution crystal structures of primitive
      orthorhombic (CypD-o) and primitive tetragonal (CypD-t) forms have been
      determined to 1.45 and 0.85 A resolution, respectively, and are nearly identical
      structurally. Although an isomorphous structure of CypD-t has previously been
      reported, the structure reported here was determined at atomic resolution, while
      CypD-o represents a new crystal form for this protein. In addition, each crystal
      form contains a PEG 400 molecule bound to the same region along with a second PEG
      400 site in CypD-t which occupies the cyclosporine A inhibitor binding site of
      CypD. Highly precise structural information for CypD should be extremely useful
      for discerning the detailed interaction of small molecules, particularly drugs
      and/or inhibitors, bound to CypD. The 0.85 A resolution structure of CypD-t is
      the highest to date for any CypD structure. 

PMID- 24915081
TI  - Crystallization and preliminary X-ray diffraction analysis of AntE, a crotonyl
      CoA carboxylase/reductase from Streptomyces sp. NRRL 2288.
AB  - AntE from Streptomyces sp. NRRL 2288 is a crotonyl-CoA carboxylase/reductase that
      catalyzes the reductive carboxylation of various alpha,beta-unsaturated acyl-CoAs
      to provide the building block at the C7 position for antimycin A biosynthesis.
      Recombinant AntE expressed in Escherichia coli was crystallized by the sitting
      drop vapour-diffusion method. The crystals belonged to space group I222 or
      I212121, with unit-cell parameters a=76.4, b=96.7, c=129.6 A,
      alpha=beta=gamma=90.0 degrees . A diffraction data set was collected at the KEK
      Photon Factory to 2.29 A resolution.

PMID- 24915082
TI  - Crystallization and preliminary crystallographic studies of PotA, a membrane
      associated ATPase of the spermidine-preferential uptake system in Thermotoga
      maritima.
AB  - A membrane-associated ATPase, PotA, is a component of the spermidine-preferential
      uptake system in prokaryotes that plays an important role in normal cell growth
      by regulating the cellular polyamine concentration. No three-dimensional
      structures of membrane-associated ATPases in polyamine-uptake systems have been
      determined to date. Here, the crystallization and preliminary X-ray diffraction
      analysis of PotA from Thermotoga maritima are reported. Diffraction data were
      collected and processed to 2.7 A resolution from both native and selenomethionine
      labelled crystals. Preliminary crystallographic analysis revealed that the
      crystals belonged to the hexagonal space group P3112 (or P3212), with unit-cell
      parameters a=b=88.9, c=221.2 A, alpha=90, beta=90, gamma=120 degrees , indicating
      that a dimer was present in the asymmetric unit.

PMID- 24915083
TI  - Complex assembly, crystallization and preliminary X-ray crystallographic analysis
      of the bovine CD8alphaalpha-BoLA-2*02201 complex.
AB  - In order to clarify the structural characteristics of the bovine MHC class I
      molecule (BoLA-I) complexed with CD8alphaalpha (CD8alphaalpha-BoLA-I), bovine
      CD8alphaalpha, BoLA-I (BoLA-2*02201) and beta2m were expressed and purified, and
      were then assembled with a peptide derived from Foot-and-mouth disease virus
      (FMDV-VP1YY9) and crystallized. The crystal diffracted to 1.7 A resolution and
      belonged to space group P21, with unit-cell parameters a=53.9, b=103.8, c=61.8 A,
      alpha=gamma=90, beta=96 degrees . The asymmetric unit contained one complex, with
      a Matthews coefficient of 2.41 A3 Da(-1) and a solvent content of 48.9%. The
      rotation-function Z-score and translation-function Z-score for molecular
      replacement were 3.4 and 8.9, respectively. In addition, SDS-PAGE analysis of
      CD8alphaalpha-BoLA-I crystals showed three bands corresponding to the molecular
      weights of BoLA-I heavy chain, beta2m and CD8alpha. The structure of the
      CD8alphaalpha-BoLA-I complex should be helpful in obtaining insight into the
      interaction between bovine CD8alphaalpha and MHC class I molecules. Structure
      determination of BoLA-2*02201-FMDV-VP1YY9 will be useful in the design of
      vaccines for foot-and-mouth disease.

PMID- 24915084
TI  - Crystallization and preliminary X-ray crystallographic analysis of carboxyl
      terminal region 4 of SigR from Streptomyces coelicolor A3(2).
AB  - Full-length SigR from Streptomyces coelicolor A3(2) was overexpressed in
      Escherichia coli, purified and submitted to crystallization trials using either
      polyethylene glycol 3350 or 4000 as a precipitant. X-ray diffraction data were
      collected to 2.60 A resolution under cryoconditions using synchrotron X-rays. The
      crystal packs in space group P43212, with unit-cell parameters a=b=42.14,
      c=102.02 A. According to the Matthews coefficient, the crystal asymmetric unit
      cannot contain the full-length protein. Molecular replacement with the known
      structures of region 2 and region 4 as independent search models indicates that
      the crystal contains only the -35 element-binding carboxyl-terminal region 4 of
      full-length SigR. Mass-spectrometric analysis of the harvested crystal confirms
      this, suggesting a crystal volume per protein weight (VM) of 2.24 A3 Da(-1) and
      45.1% solvent content.

PMID- 24915085
TI  - Expression, purification and preliminary crystallographic analysis of
      Mycobacterium tuberculosis CysQ, a phosphatase involved in sulfur metabolism.
AB  - CysQ is part of the sulfur-activation pathway that dephosphorylates 3'
      phosphoadenosine 5'-monophosphate (PAP) to regenerate adenosine 5'-monophosphate
      (AMP) and free phosphate. PAP is the product of sulfate-transfer reactions from
      sulfotransferases that use the universal sulfate donor 3'-phosphoadenosine 5'
      phosphosulfate (PAPS). In some organisms PAP is also the product of PAPS
      reductases that reduce sulfate from PAPS to sulfite. CysQ from Mycobacterium
      tuberculosis, which plays an important role in the biosynthesis of sulfated
      glycoconjugates, was successfully purified and crystallized in 24% PEG 1500, 20%
      glycerol. X-ray diffraction data were collected to 1.7 A resolution using a
      synchrotron-radiation source. Crystals grew in the orthorhombic space group
      P212121, with unit-cell parameters a=40.3, b=57.9, c=101.7 A and with one monomer
      per asymmetric unit.

PMID- 24915087
TI  - Crystallization and preliminary crystallographic analysis of defective pollen
      wall (DPW) protein from Oryza sativa.
AB  - The defective pollen wall (dpw) gene of Oryza sativa encodes a fatty acid
      reductase (DPW) which plays important roles in primary fatty alcohol synthesis.
      DPW catalyzes the synthesis of 1-hexadecanol. The enzyme shows a higher
      specificity for palmitoyl-ACP than for palmitoyl-CoA as the substrate, and can
      only use NADPH as the cofactor. To gain an understanding of the molecular
      mechanism underlying the reaction catalyzed by DPW, the gene encoding DPW without
      the N-terminal 80 amino acids (DPWDelta80) was cloned into pET-28a vector and was
      overexpressed in Escherichia coli. DPWDelta80 was purified to homogeneity and
      screened for crystallization. DPWDelta80 in complex with NADPH produced crystals
      that diffracted X-rays to a resolution of 3.4 A. The crystals belonged to space
      group P61 or P65, with unit-cell parameters a=b=222.8, c=114.0 A, alpha=beta=90,
      gamma=120 degrees .

PMID- 24915086
TI  - Overproduction, purification, crystallization and preliminary X-ray
      characterization of the family 46 carbohydrate-binding module (CBM46) of endo
      beta-1,4-glucanase B (CelB) from Bacillus halodurans.
AB  - Plant cell-wall polysaccharides offer an abundant energy source utilized by many
      microorganisms, thus playing a central role in carbon recycling. Aerobic
      microorganisms secrete carbohydrate-active enzymes (CAZymes) that catabolize this
      composite structure, comprising cellulose, hemicellulose and lignin, into simple
      compounds such as glucose. Carbohydrate-binding modules (CBMs) enhance the
      efficacy of associated CAZYmes. They are organized into families based on primary
      sequence homology. CBM family 46 contains more than 40 different members, but has
      yet to be fully characterized. Here, a recombinant derivative of the C-terminal
      family 46 CBM module (BhCBM46) of Bacillus halodurans endo-beta-1,4-glucanase B
      (CelB) was overexpressed in Escherichia coli and purified by immobilized metal
      ion affinity chromatography. Preliminary structural characterization was carried
      out on BhCBM46 crystallized in different conditions. The crystals of BhCBM46
      belonged to the tetragonal space group I4122. Data were collected for the native
      form and a selenomethionine derivative to 2.46 and 2.3 A resolution,
      respectively. The BhCBM46 structure was determined by a single-wavelength
      anomalous dispersion experiment using AutoSol from the PHENIX suite.

PMID- 24915088
TI  - Crystallization and preliminary X-ray crystallographic studies of the ArsI C-As
      lyase from Thermomonospora curvata.
AB  - Arsenic is a ubiquitous and carcinogenic environmental element that enters the
      biosphere primarily from geochemical sources, but also through anthropogenic
      activities. Microorganisms play an important role in the arsenic biogeochemical
      cycle by biotransformation of inorganic arsenic into organic arsenicals and vice
      versa. ArsI is a microbial nonheme ferrous-dependent dioxygenase that transforms
      toxic methylarsonous acid to the less toxic inorganic arsenite by C-As bond
      cleavage. An ArsI ortholog from the thermophilic bacterium Thermomonospora
      curvata was expressed, purified and crystallized. The crystals diffracted to 1.46
      A resolution and belonged to space group P43212 or its enantiomer P41212, with
      unit-cell parameters a=b=42.2, c=118.5 A.

PMID- 24915089
TI  - Characterization, crystallization and preliminary X-ray crystallographic analysis
      of the Uba5 fragment necessary for high-efficiency activation of Ufm1.
AB  - Uba5 is the smallest ubiquitin-like molecule-activating enzyme and contains an
      adenylation domain and a C-terminal region. This enzyme only exists in
      multicellular organisms. The mechanism through which the enzyme recognizes and
      activates ubiquitin-fold modifier 1 (Ufm1) remains unknown. In this study, Uba5
      adenylation domains with different C-terminal region lengths were cloned,
      expressed and purified. The results of an in vitro truncation assay suggest that
      Uba5 residues 57-363 comprise the minimal fragment required for the high
      efficiency activation of Ufm1. Crystallization of Uba5 residues 57-363 was
      performed at 277 K using PEG 3350 as the precipitant, and crystals optimized by
      microseeding diffracted to 2.95 A resolution, with unit-cell parameters
      a=b=97.66, c=144.83 A, alpha=beta=90, gamma=120 degrees . There is one molecule
      in the asymmetric unit; the Matthews coefficient and the solvent content were
      calculated to be 2.93 A3 Da(-1) and 58.1%, respectively.

PMID- 24915090
TI  - Crystallization and preliminary X-ray diffraction analysis of proximal thread
      matrix protein 1 (PTMP1) from Mytilus galloprovincialis.
AB  - In order to deal with the dynamic ocean environment, blue mussels adhere to
      various surfaces via their collagenous byssal threads. PTMP1 (proximal thread
      matrix protein 1) is one identified matrix protein residing in the proximal
      thread and is capable of collagen binding. Its sequence comprises two von
      Willebrand factor type A-like repeats. In order to characterize the structure and
      domain architecture of PTMP1, recombinant protein was crystallized by vapour
      diffusion. The obtained crystals diffracted to 1.95 A resolution and belonged to
      space group P21, with unit-cell parameters a=62.0, b=62.3, c=122.6 A, beta=102.2
      degrees . The Matthews coefficient suggested the presence of two monomers in the
      asymmetric unit and 48.3% solvent content.

PMID- 24915091
TI  - Crystallization and preliminary X-ray diffraction analysis of Hypocrea jecorina
      Cel7A in two new crystal forms.
AB  - Cel7A (previously known as cellobiohydrolase I) from Hypocrea jecorina was
      crystallized in two crystalline forms, neither of which have been previously
      reported. Both forms co-crystallize under the same crystallization conditions.
      The first crystal form belonged to space group C2, with unit-cell parameters
      a=152.5, b=44.9, c=57.6 A, beta=101.2 degrees , and diffracted X-rays to 1.5 A
      resolution. The second crystal form belonged to space group P6322, with unit-cell
      parameters a=b?155, c?138 A, and diffracted X-rays to 2.5 A resolution. The
      crystals were obtained using full-length Cel7A, which consists of a large 434
      residue N-terminal catalytic domain capable of cleaving cellulose, a 27-residue
      flexible linker and a small 36-residue C-terminal carbohydrate-binding module
      (CBM). However, a preliminary analysis of the electron-density maps suggests that
      the linker and CBM are disordered in both crystal forms. Complete refinement and
      structure analysis are currently in progress.

PMID- 24915092
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction analysis of a ferredoxin/flavodoxin-NADP(H) oxidoreductase (Bc0385)
      from Bacillus cereus.
AB  - Ferredoxin/flavodoxin-NADP(H) oxidoreductases (FNRs) are key enzymes involved in
      catalysing electron transfer between ferredoxins/flavodoxins and NAD(P)H/NAD(P)+.
      In Bacillus cereus there are three genes that may encode FNRs, and the Bc0385 FNR
      has been cloned, overexpressed, purified and successfully crystallized in its
      NADPH/NADP+-free form. Diffraction data have been collected to 2.5 A resolution
      from crystals belonging to the orthorhombic space group P21212, with unit-cell
      parameters a=57.2, b=164.3, c=95.0 A, containing two FNR molecules in the
      asymmetric unit. The structure of the Bc0385 FNR has been solved by molecular
      replacement, and is a member of the homodimeric thioredoxin reductase-like class
      of FNRs.

PMID- 24915093
TI  - Crystallization and preliminary X-ray crystallographic studies of
      dehydroascorbate reductase (DHAR) from Oryza sativa L. japonica.
AB  - Dehydroascorbate reductase from Oryza sativa L. japonica (OsDHAR), a key enzyme
      in the regeneration of vitamin C, maintains reduced pools of ascorbic acid to
      detoxify reactive oxygen species. In previous studies, the overexpression of
      OsDHAR in transgenic rice increased grain yield and biomass as well as the amount
      of ascorbate, suggesting that ascorbate levels are directly associated with crop
      production in rice. Hence, it has been speculated that the increased level of
      antioxidants generated by OsDHAR protects rice from oxidative damage and
      increases the yield of rice grains. However, the crystal structure and detailed
      mechanisms of this important enzyme need to be further elucidated. In this study,
      recombinant OsDHAR protein was purified and crystallized using the sitting-drop
      vapour-diffusion method at pH 8.0 and 298 K. Plate-shaped crystals were obtained
      using 0.15 M potassium bromide, 30%(w/v) PEG MME 2000 as a precipitant, and the
      crystals diffracted to a resolution of 1.9 A on beamline 5C at the Pohang
      Accelerator Laboratory. The X-ray diffraction data indicated that the crystal
      contained one OsDHAR molecule in the asymmetric unit and belonged to space group
      P21 with unit-cell parameters a=47.03, b=48.38, c=51.83 A, beta=107.41 degrees .

PMID- 24915094
TI  - Expression, purification, crystallization and preliminary X-ray analysis of the
      HER3-9E12 Fab complex.
AB  - 9E12 is a fully human immunoglobulin G1/kappa monoclonal antibody that is
      specific for the epidermal growth factor receptor 3 (HER3), the overexpression of
      which has been detected in many tumour types and is associated with poor survival
      outcomes. To date, knowledge of the molecular mechanism for targeted antibodies
      that directly inhibit HER3 signalling is limited. Because knowledge of such
      therapeutic antibodies would help basic immunological therapeutics, structural
      insights into the HER3-9E12 Fab complex are important. Recombinant human HER3 and
      Fab fragments of the 9E12 antibody were cloned, expressed and crystallized, and
      crystallographic data sets were collected. The crystals belonged to space group
      P1, with unit-cell parameters a=74.4, b=98.6, c=99.6 A, alpha=106.0, beta=95.0,
      gamma=102.5 degrees  and diffracted to a resolution of 2.1 A.

PMID- 24915095
TI  - Crystallization and preliminary X-ray crystallographic analysis of a bacterial
      Asn-transamidosome.
AB  - Most canonical aminoacyl-tRNAs are synthesized directly by their cognate
      aminoacyl-tRNA synthetases (aaRSs), but glutaminyl-tRNA(Gln) and asparaginyl
      tRNA(Asn) are synthesized indirectly by two-step processes. These processes are
      catalyzed by the transamidosome, a large ribonucleoprotein particle composed of
      GatA, GatB, GatC, aaRS and tRNA. In this study, the Asn-transamidosome from
      Pseudomonas aeruginosa was reconstructed and crystallized by mixing purified
      GatCAB complex, AspRS and tRNA(Asn). The crystal of the Asn-transamidosome
      belonged to space group P21, with unit-cell parameters a=93.3, b=186.0, c=287.8
      A, beta=93.3 degrees , and diffracted to 3.73 A resolution. Preliminary X-ray
      crystallographic analysis showed that the asymmetric unit contained two Asn
      transamidosomes, each composed of two GatCABs, one AspRS dimer and two tRNAAsns,
      indicating that the construction of the current Asn-transamidosome differs from
      that of Thermus thermophilus.

PMID- 24915096
TI  - Expression, purification, crystallization and preliminary X-ray crystallographic
      analysis of Enpp6.
AB  - Enpp (ectonucleotide phosphodiesterase/pyrophosphatase) 6 is a membrane-bound
      glycoprotein that hydrolyzes choline-containing compounds such as
      lysophosphatidylcholine and glycerophosphorylcholine, and presumably participates
      in choline metabolism. The catalytic domain of mouse Enpp6 was expressed in
      HEK293T cells, purified using the TARGET tag/P20.1-Sepharose system and
      crystallized. An X-ray diffraction data set was collected to 1.8 A resolution.
      The crystal belonged to space group P1, with unit-cell parameters a=63.7, b=68.8,
      c=69.7 A, alpha=60.6, beta=87.0, gamma=68.1 degrees . Assuming the presence of
      two protein molecules per asymmetric unit, the solvent content was estimated to
      be 49.5%.

PMID- 24915097
TI  - Crystallization and preliminary X-ray diffraction analysis of (R)-carbonyl
      reductase from Candida parapsilosis.
AB  - The NADH-dependent (R)-carbonyl reductase from Candida parapsilosis (RCR)
      catalyzes the asymmetric reduction of 2-hydroxyacetophenone (HAP) to produce (R)
      1-phenyl-1,2-ethanediol [(R)-PED], which is used as a versatile building block
      for the synthesis of pharmaceuticals and fine chemicals. To gain insight into the
      catalytic mechanism, the structures of complexes of RCR with ligands, including
      the coenzyme, are important. Here, the recombinant RCR protein was expressed and
      purified in Escherichia coli and was crystallized in the presence of NAD+. The
      crystals, which belonged to the orthorhombic space group P212121, with unit-cell
      parameters a=85.64, b=106.11, c=145.55 A, were obtained by the sitting-drop
      vapour-diffusion method and diffracted to 2.15 A resolution. Initial model
      building indicates that RCR forms a homotetramer, consistent with previous
      reports of medium-chain-type alcohol dehydrogenases.

PMID- 24915098
TI  - Preliminary crystallographic studies of a Schistosoma mansoni antigen (Sm21.7)
      dynein light-chain (DLC) domain.
AB  - Schistosomiasis is an inflammatory chronic disease that represents a major health
      problem in tropical and subtropical countries. The drug of choice for treatment,
      praziquantel, is effective in killing adult worms but fails to kill immature
      forms and prevent reinfection. One prominent antigen candidate for an anti
      schistosomiasis vaccine is the protein Sm21.7 (184 amino-acid residues) from
      Schistosoma mansoni, a tegumental protein capable of reducing the worm burden in
      a murine immunization model. In the present work, the Sm21.7 gene was cloned and
      expressed in Escherichia coli and the full-length protein was purified to
      homogeneity. Crystals of recombinant Sm21.7 suitable for X-ray diffraction were
      obtained using PEG monomethyl ether 2000 as a precipitant. X-ray diffraction
      images of a native crystal (at 2.05 A resolution) and a quick-cryosoaked NaI
      derivative (at 1.95 A resolution) were collected on the W01B-MX2 beamline at the
      Laboratorio Nacional de Luz Sincrotron (LNLS, Brazilian Synchrotron Light
      Laboratory/MCT). Both crystals belonged to the hexagonal space group P6122, with
      similar unit-cell parameters a=b=108.5, c=55.8 A. SIRAS-derived phases were used
      to generate the first electron-density map, from which a partial three
      dimensional model of Sm21.7 (from Gln89 to Asn184) was automatically constructed.
      Anaysis of dissolved crystals by SDS-PAGE confirmed that the protein was cleaved
      in the crystallization drop and only the Sm21.7 C-terminal domain was
      crystallized. The structure of the Sm21.7 C-terminal domain will help in the
      localization of the epitopes responsible for its protective immune responses,
      constituting important progress in the development of an anti-schistosomiasis
      vaccine.

PMID- 24915099
TI  - Crystallization and preliminary X-ray diffraction analysis of the peripheral
      light-harvesting complex LH2 from Marichromatium purpuratum.
AB  - LH2 from the purple photosynthetic bacterium Marichromatium (formerly known as
      Chromatium) purpuratum is an integral membrane pigment-protein complex that is
      involved in harvesting light energy and transferring it to the LH1-RC 'core'
      complex. The purified LH2 complex was crystallized using the sitting-drop vapour
      diffusion method at 294 K. The crystals diffracted to a resolution of 6 A using
      synchrotron radiation and belonged to the tetragonal space group I4, with unit
      cell parameters a=b=109.36, c=80.45 A. The data appeared to be twinned, producing
      apparent diffraction symmetry I422. The tetragonal symmetry of the unit cell and
      diffraction for the crystals of the LH2 complex from this species reveal that
      this complex is an octamer.

PMID- 24915100
TI  - Preliminary joint X-ray and neutron protein crystallographic studies of ecDHFR
      complexed with folate and NADP+.
AB  - A crystal of Escherichia coli dihydrofolate reductase (ecDHFR) complexed with
      folate and NADP+ of 4*1.3*0.7 mm (3.6 mm3) in size was obtained by sequential
      application of microseeding and macroseeding. A neutron diffraction data set was
      collected to 2.0 A resolution using the IMAGINE diffractometer at the High Flux
      Isotope Reactor within Oak Ridge National Laboratory. A 1.6 A resolution X-ray
      data set was also collected from a smaller crystal at room temperature. The
      neutron and X-ray data were used together for joint refinement of the ecDHFR
      folate-NADP+ ternary-complex structure in order to examine the protonation state,
      protein dynamics and solvent structure of the complex, furthering understanding
      of the catalytic mechanism.

PMID- 24915101
TI  - Preliminary time-of-flight neutron diffraction studies of Escherichia coli ABC
      transport receptor phosphate-binding protein at the Protein Crystallography
      Station.
AB  - Inorganic phosphate is an essential molecule for all known life. Organisms have
      developed many mechanisms to ensure an adequate supply, even in low-phosphate
      conditions. In prokaryotes phosphate transport is instigated by the phosphate
      binding protein (PBP), the initial receptor for the ATP-binding cassette (ABC)
      phosphate transporter. In the crystal structure of the PBP-phosphate complex, the
      phosphate is completely desolvated and sequestered in a deep cleft and is bound
      by 13 hydrogen bonds: 12 to protein NH and OH donor groups and one to a
      carboxylate acceptor group. The carboxylate plays a key recognition role by
      accepting a phosphate hydrogen. PBP phosphate affinity is relatively consistent
      across a broad pH range, indicating the capacity to bind monobasic (H2PO4-) and
      dibasic (HPO4(2-)) phosphate; however, the mechanism by which it might
      accommodate the second hydrogen of monobasic phosphate is unclear. To answer this
      question, neutron diffraction studies were initiated. Large single crystals with
      a volume of 8 mm3 were grown and subjected to hydrogen/deuterium exchange. A 2.5
      A resolution data set was collected on the Protein Crystallography Station at the
      Los Alamos Neutron Science Center. Initial refinement of the neutron data shows
      significant nuclear density, and refinement is ongoing. This is the first report
      of a neutron study from this superfamily.

PMID- 24915102
TI  - Crystallization and preliminary X-ray characterization of the 2,4'
      dihydroxyacetophenone dioxygenase from Alcaligenes sp. 4HAP.
AB  - The enzyme 2,4'-dihydroxyacetophenone dioxygenase (or DAD) catalyses the
      conversion of 2,4'-dihydroxyacetophenone to 4-hydroxybenzoic acid and formic acid
      with the incorporation of molecular oxygen. Whilst the vast majority of
      dioxygenases cleave within the aromatic ring of the substrate, DAD is very
      unusual in that it is involved in C-C bond cleavage in a substituent of the
      aromatic ring. There is evidence that the enzyme is a homotetramer of 20.3 kDa
      subunits each containing nonhaem iron and its sequence suggests that it belongs
      to the cupin family of dioxygenases. By the use of limited chymotrypsinolysis,
      the DAD enzyme from Alcaligenes sp. 4HAP has been crystallized in a form that
      diffracts synchrotron radiation to a resolution of 2.2 A. 

PMID- 24915103
TI  - Protein expression, characterization, crystallization and preliminary X-ray
      crystallographic analysis of a Fic protein from Clostridium difficile.
AB  - Fic domains in proteins are found in abundance in nature from the simplest
      prokaryotes to animals. Interestingly, Fic domains found in two virulence factors
      of Gram-negative bacteria have recently been demonstrated to catalyse the
      transfer of the AMP moiety from ATP to small host GTPases. This post
      translational modification has attracted considerable interest and a role for
      adenylylation in pathology and physiology is emerging. This work was aimed at the
      structural characterization of a newly identified Fic protein of the Gram
      positive bacterium Clostridium difficile. A constitutively active inhibitory
      helix mutant of C. difficile Fic was overexpressed in Escherichia coli, purified
      and crystallized by the vapour-diffusion technique. Preliminary X-ray
      crystallographic analysis shows that the crystals diffract to at least 1.68 A
      resolution at a synchrotron X-ray source. The crystals belonged to the
      orthorhombic space group P212121, with unit-cell parameters a=45.6, b=80.8,
      c=144.7 A, alpha=beta=gamma=90 degrees . Two molecules per asymmetric unit
      corresponds to a Matthews coefficient of 2.37 A3 Da(-1) and a solvent content of
      48%.

PMID- 24915104
TI  - Crystallization and preliminary X-ray crystallographic analysis of polyphenol
      oxidase from Juglans regia (jrPPO1).
AB  - Tyrosinase is a type 3 copper enzyme that catalyzes the ortho-hydroxylation of
      monophenols to diphenols as well as their subsequent oxidation to quinones, which
      are precursors for the biosynthesis of melanins. The first plant tyrosinase from
      walnut leaves (Juglans regia) was purified to homogeneity and crystallized.
      During the purification, two forms of the enzyme differing only in their C
      termini [jrPPO1(Asp101-Pro444) and jrPPO1(Asp101-Arg445)] were obtained. The most
      abundant form jrPPO1(Asp101-Arg445), as described in Zekiri et al.
      [Phytochemistry (2014), 101, 5-15], was crystallized, resulting in crystals that
      belonged to space group C121, with unit-cell parameters a=115.56, b=91.90,
      c=86.87 A, alpha=90, beta=130.186, gamma=90 degrees , and diffracted to 2.39 A
      resolution. Crystals were only obtained from solutions containing at least 30%
      polyethylene glycol 5000 monomethyl ether in a close-to-neutral pH range.

PMID- 24915105
TI  - Reasons for ICU demand and long-term follow-up of a chronic obstructive pulmonary
      disease cohort.
AB  - Acute respiratory failure (ARF) can necessitate mechanical ventilation and
      intensive care unit (ICU) admission in patients with COPD. We evaluated the
      reasons COPD patients are admitted to the ICU and assessed long-term outcomes in
      a retrospective cohort study in a respiratory level-III ICU of a teaching
      government hospital between November 2007 and April 2012. All COPD patients
      admitted to ICU for the first time were enrolled and followed for 12 months.
      Patient characteristics, body mass index (BMI), long-term oxygen therapy (LTOT),
      non-invasive ventilation (LT-NIV) at home, COPD co-morbidities, reasons for ICU
      admission, ICU data, length of stay, prescription of new LTOT and LT-NIV, and ICU
      mortality were recorded. Patient survival after ICU discharge was evaluated by
      Kaplan-Meier survival analysis. A total of 962 (710 male) patients were included.
      The mean age was 70 (SD 10). The major reasons for ICU admission were COPD
      exacerbation (66.7%) and pneumonia (19.7%). ICU and hospital mortality were
      11.4%, 12.5% respectively, and 842 patients were followed-up. The new LT-NIV
      prescription rate was 15.8%. The 6-month 1, 2, 3, and 5-year mortality rates were
      24.5%, 33.7%, 46.9%, 58.9% and 72.5%, respectively. Long-term survival was
      negatively affected by arrhythmia (p < 0.013) and pneumonia (p < 0.025). LT-NIV
      use (p < 0.016) with LTOT (p < 0.038) increase survival. Pulmonary infection can
      be a major reason for ICU admission and determining outcome after ICU discharge.
      Unlike arrhythmia and pneumonia, LT-NIV can improve long-term survival in
      eligible COPD patients.

PMID- 24915106
TI  - The influence of pitch dimensions on performance during small-sided and
      conditioned soccer games.
AB  - This study examined the influence of pitch dimensions in small-sided soccer games
      in shaping opportunities for performers to maintain ball possession, pass to
      teammates and shoot at goal. Fifteen amateur standard male participants (M =
      21.87, sigma = 1.96 years) played 5 v 5 small-sided soccer games in three varying
      pitch conditions (28 m * 14 m, 40 m * 20 m and 52 m * 26 m). Thirty sequences of
      play in each condition were selected for digitisation using TACTO software,
      allowing the capture of bi-dimensional displacement coordinate data of all
      players and the ball. The values of interpersonal distance between all attackers
      and immediate defenders and the relative distances of defenders to intercept a
      shot and a pass were computed as dependent variables. Results showed existence of
      fewer opportunities to maintain ball possession on smaller pitches, compared to
      medium and larger pitches. Conversely, the different dimensions set to the pitch
      did not influence opportunities for players to shoot at goal, or to perform
      passes to other teammates. By examining the specific spatial-temporal
      relationships of players and key-task constraints, the data from this study
      explain how effects of manipulating pitch dimensions of small-sided games might
      enhance opportunities for acquiring specific movement and decision-making skills.

PMID- 24915107
TI  - Tailoring polymersome bilayer permeability improves enhanced permeability and
      retention effect for bioimaging.
AB  - Self-assembled nanoparticles conjugated with various imaging contrast agents have
      been used for the detection and imaging of pathologic tissues. Inadvertently,
      these nanoparticles undergo fast, dilution-induced disintegration in circulation
      and quickly lose their capability to associate with and image the site of
      interest. To resolve this challenge, we hypothesize that decreasing the bilayer
      permeability of polymersomes can stabilize their structure, extend their lifetime
      in circulation, and hence improve the quality of bioimaging when the polymersome
      is coupled with an imaging probe. This hypothesis is examined by using poly(2
      hydroxyethyl-co-octadecyl aspartamide), sequentially modified with methacrylate
      groups, to build model polymersomes. The bilayer permeability of the polymersome
      is decreased by increasing the packing density of the bilayer with methacrylate
      groups and is further decreased by inducing chemical cross-linking reactions
      between the methacrylate groups. The polymersome with decreased bilayer
      permeability demonstrates greater particle stability in physiological media and
      ultimately can better highlight tumors in mice over 2 days compared to those with
      higher bilayer permeability after labeling with a near-infrared (NIR) fluorescent
      probe. We envisage that the resulting nanoparticles will not only improve
      diagnosis but also further image-guided therapies. 

PMID- 24915108
TI  - RETRACTED: Protective role of HSP70 against various gastrointestinal diseases.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). This article has been
      retracted at the request of the author. The article is a substantial duplicate of
      a paper that has already been published by the same author in Curr Pharm Des, 16
      (2010) 1190-1196, http://dx.doi.org/10.2174/138161210790945986. 

PMID- 24915110
TI  - The impacts of triclosan on anaerobic community structures, function, and
      antimicrobial resistance.
AB  - Triclosan is a widespread antimicrobial agent that accumulates in anaerobic
      digesters used to treat the residual solids generated at municipal wastewater
      treatment plants; there is very little information, however, about how triclosan
      impacts microbial communities in anaerobic digesters. We investigated how
      triclosan impacts the community structure, function and antimicrobial resistance
      genes in lab-scale anaerobic digesters. Previously exposed (to triclosan)
      communities were amended with 5, 50, and 500 mg/kg of triclosan, corresponding to
      the median, 95th percentile, and 4-fold higher than maximum triclosan
      concentration that has been detected in U.S. biosolids. Triclosan amendment
      caused all of the Bacteria and Archaea communities to structurally diverge from
      that of the control cultures (based on ARISA). At the end of the experiment, all
      triclosan-amended Archaea communities had diverged from the control communities,
      regardless of the triclosan concentration added. In contrast, over time the
      Bacteria communities that were amended with lower concentrations of triclosan (5
      mg/kg and 50 mg/kg) initially diverged and then reconverged with the control
      community structure. Methane production at 500 mg/kg was nearly half the methane
      production in control cultures. At 50 mg/kg, a large variability in methane
      production was observed, suggesting that 50 mg/kg may be a tipping point where
      function begins to fail in some communities. When previously unexposed
      communities were exposed to 500 mg triclosan/kg, function was maintained, but the
      abundance of a gene encoding for triclosan resistance (mexB) increased. This
      research suggests that triclosan could inhibit methane production in anaerobic
      digesters if concentrations were to increase and may also select for resistant
      Bacteria. In both cases, microbial community composition and exposure history
      alter the influence of triclosan. 

PMID- 24915109
TI  - Cyanuric acid hydrolase from Azorhizobium caulinodans ORS 571: crystal structure
      and insights into a new class of Ser-Lys dyad proteins.
AB  - Cyanuric acid hydrolase (CAH) catalyzes the hydrolytic ring-opening of cyanuric
      acid (2,4,6-trihydroxy-1,3,5-triazine), an intermediate in s-triazine bacterial
      degradation and a by-product from disinfection with trichloroisocyanuric acid. In
      the present study, an X-ray crystal structure of the CAH-barbituric acid
      inhibitor complex from Azorhizobium caulinodans ORS 571 has been determined at
      2.7 A resolution. The CAH protein fold consists of three structurally homologous
      domains forming a beta-barrel-like structure with external alpha-helices that
      result in a three-fold symmetry, a dominant feature of the structure and active
      site that mirrors the three-fold symmetrical shape of the substrate cyanuric
      acid. The active site structure of CAH is similar to that of the recently
      determined AtzD with three pairs of active site Ser-Lys dyads. In order to
      determine the role of each Ser-Lys dyad in catalysis, a mutational study using a
      highly sensitive, enzyme-coupled assay was conducted. The 109-fold loss of
      activity by the S226A mutant was at least ten times lower than that of the S79A
      and S333A mutants. In addition, bioinformatics analysis revealed the
      Ser226/Lys156 dyad as the only absolutely conserved dyad in the CAH/barbiturase
      family. These data suggest that Lys156 activates the Ser226 nucleophile which can
      then attack the substrate carbonyl. Our combination of structural, mutational,
      and bioinformatics analyses differentiates this study and provides experimental
      data for mechanistic insights into this unique protein family.

PMID- 24915111
TI  - Hydrogen peroxide-induced antioxidant activities and cardiotonic glycoside
      accumulation in callus cultures of endemic Digitalis species.
AB  - The effect of hydrogen peroxide (H2O2) on callus cultures of four Digitalis
      species (Digitalis lamarckii, Digitalis trojana, Digitalis davisiana and
      Digitalis cariensis) increased catalase (CAT), superoxide dismutase (SOD), total
      phenolic, proline activity and cardiotonic glycoside production. Callus derived
      from hypocotyl explants was cultured on Murashige and Skoog medium supplemented
      with 0.25 mg L(-1) indole-3-acetic acid (IAA) and 0.5 mg L(-1) thidiazuron (TDZ).
      After a month of culture, callus was transferred to MS medium containing 10 mM
      H2O2 and then incubated for 6 h. The amount of five cardenolides (Lanatoside C,
      Digitoxin, Digoxigenin, Gitoxigenin and Digoxin) as well as CAT, SOD, total
      phenolic, proline activity from Digitalis species were compared. No digoxin was
      detected in all treatments and control groups. The total cardenolides estimated
      were in the order of D. lamarckii (586.65  MUg g(-1) dw), D. davisiana (506.79
      MUg g(-1) dw), D. cariensis (376.60 MUg g(-1) dw) and D. trojana (282.39 MUg g(
      1) dw). It was clear that H2O2 pre-treatment resulted in an increase in enzymatic
      and nonenzymatic antioxidants. However, a significant negative relationship
      between cardenolides production and overall activities of CAT, SOD, total
      phenolic and proline was evident. The described protocol here will be useful for
      the development of new strategies for a large-scale production of cardenolides. 

PMID- 24915112
TI  - Factors that drive peptide assembly from native to amyloid structures:
      experimental and theoretical analysis of [leu-5]-enkephalin mutants.
AB  - Five different mutants of [Leu-5] Enkephalin YGGFL peptide have been investigated
      for fibril formation propensities. The early oligomer structures have been probed
      with a combination of ion-mobility mass spectrometry and computational modeling.
      The two peptides YVIFL and YVVFL form oligomers and amyloid-like fibrils. YVVFV
      shows an early stage oligomer distribution similar to those of the previous two,
      but amyloid-like aggregates are less abundant. Atomic resolution X-ray structures
      of YVVFV show two different modes of interactions at the dry interface between
      steric zippers and pairs of antiparallel beta-sheets, but both are less favorable
      than the packing motif found in YVVFL. Both YVVFV and YVVFL can form a Class 6
      steric zipper. However, in YVVFV, the strands between mating sheets are parallel
      to each other and in YVVFL they are antiparallel. The overall data highlight the
      importance of structurally characterizing high order oligomers within
      oligomerization pathways in studies of nanostructure assembly. 

PMID- 24915114
TI  - Investigating uranium distribution in surface sediments and waters: a case study
      of contamination from the Juniper Uranium Mine, Stanislaus National Forest, CA.
AB  - The uranium concentrations and isotopic compositions of waters, sediment
      leachates and sediments from Red Rock Creek in the Stanislaus National Forest of
      California were measured to investigate the transport of uranium from a point
      source (the Juniper Uranium Mine) to a natural surface stream environment. The
      ((234)U)/((238)U) composition of Red Rock Creek is altered downstream of the
      Juniper Mine. As a result of mine-derived contamination, water ((234)U)/((238)U)
      ratios are 67% lower than in water upstream of the mine (1.114-1.127 +/- 0.009 in
      the contaminated waters versus 1.676 in the clean branch of the stream), and
      sediment samples have activity ratios in equilibrium in the clean creek and out
      of equilibrium in the contaminated creek (1.041-1.102 +/- 0.007). Uranium
      concentrations in water, sediment and sediment leachates are highest downstream
      of the mine, but decrease rapidly after mixing with the clean branch of the
      stream. Uranium content and compositions of the contaminated creek headwaters
      relative to the mine tailings of the Juniper Mine suggest that uranium has been
      weathered from the mine and deposited in the creek. The distribution of uranium
      between sediment surfaces (leachable fraction) and bulk sediment suggests that
      adsorption is a key element of transfer along the creek. In clean creek samples,
      uranium is concentrated in the sediment residues, whereas in the contaminated
      creek, uranium is concentrated on the sediment surfaces (~70-80% of uranium in
      leachable fraction). Contamination only exceeds the EPA maximum contaminant level
      (MCL) for drinking water in the sample with the closest proximity to the mine.
      Isotopic characterization of the uranium in this system coupled with
      concentration measurements suggest that the current state of contamination in Red
      Rock Creek is best described by mixing between the clean creek and contaminated
      upper branch of Red Rock Creek rather than mixing directly with mine sediment. 

PMID- 24915113
TI  - Nanostructured self-assembly of inverted formin 2 (INF2) and F-actin-INF2
      complexes revealed by atomic force microscopy.
AB  - Self-organization of cytoskeletal proteins such as actin and tubulin into
      filaments and microtubules is frequently assisted by the proteins binding to
      them. Formins are regulatory proteins that nucleate the formation of new
      filaments and are essential for a wide range of cellular functions. The
      vertebrate inverted formin 2 (INF2) has both actin filament nucleating and
      severing/depolymerizing activities connected to its ability to encircle actin
      filaments. Using atomic force microscopy, we report that a formin homology 2
      (FH2) domain-containing construct of INF2 (INF2-FH1-FH2-C or INF2-FFC) self
      assembles into nanoscale ringlike oligomeric structures in the absence of actin
      filaments, demonstrating an inherent ability to reorganize from a dimeric to an
      oligomeric state. A construct lacking the C-terminal region (INF2-FH1-FH2 or INF2
      FF) also oligomerizes, confirming the dominant role of FH2-mediated interactions.
      Moreover, INF2-FFC domains were observed to organize into ringlike structures
      around single actin filaments. This is the first demonstration that formin FH2
      domains can self-assemble into oligomers in the absence of filaments and has
      important implications for observing unaveraged decoration and/or remodeling of
      filaments by actin binding proteins. 

PMID- 24915115
TI  - Time course of bone mineral density changes with denosumab compared with other
      drugs in postmenopausal osteoporosis: a dose-response-based meta-analysis.
AB  - OBJECTIVE: Our objective was to compare the time course of bone mineral density
      (BMD) changes at the lumbar spine (LS) and total hip (TH) in postmenopausal women
      during treatment with denosumab, bisphosphonates, selective estrogen receptor
      modulators, PTH, or calcitonin. DATA SOURCES AND STUDY SELECTION: Data were
      extracted from 142 randomized controlled trials for prevention or treatment of
      postmenopausal osteoporosis representing over 113,000 women. DATA EXTRACTION AND
      DATA SYNTHESIS: The percent change from baseline in BMD was analyzed using a
      nonlinear least-squares random-effects meta-regression analysis. The dose
      response relationship of BMD changes was well characterized by a maximal effect
      (EMax) model with a different EMax for LS and TH for each drug class. The ratio
      of LS and TH BMD changes was significantly different across the different drug
      classes. The time course of BMD changes was well characterized by an exponential
      onset with a different rate for LS and TH for each drug class. The dose-response
      relationship for denosumab showed that the approved dosing regimen of 60 mg every
      6 months resulted in maximal BMD changes. CONCLUSION: This exploratory analysis
      shows that 3 years of treatment with denosumab resulted in bigger changes in LS
      and TH BMD compared with 3 years of treatment with 10 mg/d oral alendronate, 5
      mg/y i.v. zoledronic acid, 5 mg/d oral risedronate, 150 mg/mo oral ibandronate, 3
      mg i.v. ibandronate every 3 months, 60 mg/d oral raloxifene, and 200 IU/d
      calcitonin. Treatment with PTH resulted in larger changes in LS BMD compared with
      denosumab; however, denosumab treatment provided larger changes in TH BMD.

PMID- 24915116
TI  - Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in
      obesity.
AB  - CONTEXT: Adipokines actuate chronic, low-grade inflammation through a complex
      network of immune markers, but the current understanding of these networks is
      incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP)
      occupies an important position in the inflammatory pathways involved in obesity.
      The pathogenetic and clinical influences of sIL1RAP are unknown. OBJECTIVE: The
      objective of the study was to elucidate whether plasma levels of sIL1RAP are
      reduced in obesity, using affluent clinical, biochemical, and genetic data from
      two diverse cohorts. DESIGN, SETTING, AND PARTICIPANTS: The study was conducted
      in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42
      families) and South Asians living in Mauritius, n = 230). MAIN OUTCOME MEASURES:
      Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP
      levels were investigated using both a large-scale gene expression profiling study
      and a genome-wide association study. RESULTS: A significant decrease in plasma
      sIL1RAP levels were observed in obese subjects, even after adjustment for age and
      sex. The sIL1RAP levels demonstrated a strong inverse association with obesity
      measures in both populations. All associations were more significant in females.
      Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP
      transcript levels (NM_134470), showed evidence for shared genetic influences with
      obesity measures and were significantly associated with the rs2885373 single
      nucleotide polymorphism (P = 6.7 * 10(-23)) within the IL1RAP gene. CONCLUSIONS:
      Plasma sIL1RAP levels are reduced in obesity and can potentially act as
      biomarkers of obesity. Mechanistic studies are required to understand the exact
      contribution of sIL1RAP to the pathogenesis of obesity.

PMID- 24915117
TI  - Denosumab for treatment of hypercalcemia of malignancy.
AB  - CONTEXT: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is
      often caused by excessive osteoclast-mediated bone resorption. Patients may not
      respond to or may relapse after iv bisphosphonate therapy. OBJECTIVE: We
      investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone
      resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM.
      DESIGN, SETTING, AND PARTICIPANTS: In this single-arm international study,
      participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL
      (3.1 mmol/L) despite bisphosphonates given >7 and <=30 days before screening.
      INTERVENTION: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and
      then every 4 weeks. MAIN OUTCOME MEASURES: The primary endpoint was the
      proportion of patients with CSC <=11.5 mg/dL (2.9 mmol/L) (response) by day 10.
      Secondary endpoints included response by visit, duration of response, and the
      proportion of patients with a complete response (CSC <=10.8 mg/dL [2.7 mmol/L])
      by day 10 and during the study. RESULTS: Patients (N = 33) had solid tumors or
      hematologic malignancies. By day 10, 21 patients (64%) reached CSC <=11.5 mg/dL,
      and 12 patients (33%) reached CSC <=10.8 mg/dL. During the study, 23 patients
      (70%) reached CSC <=11.5 mg/dL, and 21 patients (64%) reached CSC <=10.8 mg/dL.
      Estimated median response duration was 104 days. The most common serious adverse
      events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients,
      9%). CONCLUSIONS: In patients with HCM despite recent iv bisphosphonate
      treatment, denosumab lowered serum calcium in 64% of patients within 10 days,
      inducing durable responses. Denosumab may offer a new treatment option for HCM.

PMID- 24915119
TI  - Presence of brown adipose tissue in an adolescent with severe primary
      hypothyroidism.
AB  - CONTEXT: Brown adipose tissue (BAT) generates heat during adaptive thermogenesis
      in response to cold temperature. Thyroid hormone (TH) receptors, type 2
      deiodinase, and TSH receptors are present on brown adipocytes, indicating that
      the thyroid axis regulates BAT. It is unknown whether absent TH in humans would
      down-regulate development of BAT and its thermogenic function. OBJECTIVE: The
      objective of the study was to examine BAT by magnetic resonance imaging (MRI) and
      infrared thermal imaging (IRT) in a pediatric patient with severe primary
      hypothyroidism before and after TH treatment. DESIGN/SETTING: This study was a
      case report with longitudinal follow-up in a tertiary center. MAIN OUTCOME
      MEASURES: BAT fat fraction (FF) by MRI and skin temperature by IRT were measured.
      RESULTS: An 11.5-year-old female was severely hypothyroid (TSH, 989 MUIU/mL; free
      T4, 0.10 ng/dL; low thyroglobulin, 3.0 ng/mL). Low MRI measures of FF (56.1% +/-
      3.7%) indicated that BAT was abundantly present in the supraclavicular fossa. IRT
      showed higher supraclavicular temperature (36.0 degrees C +/-0.16 degrees C) than
      the suprasternal area (34.3 degrees C +/- 0.19 degrees C). After 2 months of TH
      replacement, she was euthyroid (TSH, 4.3 MUIU/mL; free T4, 1.49 ng/dL; T3, 102
      ng/dL) at which time supraclavicular BAT decreased (increased FF 60.7% +/- 3.8%).
      IRT showed a higher, more homogeneous skin temperature throughout the upper
      thorax (supraclavicular, 37.1 degrees C +/- 0.23 degrees C; suprasternal, 36.4
      degrees C +/- 0.13 degrees C). The overall size of the supraclavicular fat depot
      decreased from 84.79 cm(3) to 41.21 cm(3). CONCLUSIONS: These findings document
      the presence of BAT and thermogenesis in profound hypothyroidism and suggest a
      role for TSH and/or TRH as a potential regulator of BAT.

PMID- 24915118
TI  - Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary
      heart disease: an individual participant data analysis.
AB  - CONTEXT: Subclinical hypothyroidism has been associated with increased risk of
      coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L
      or greater. The measurement of thyroid antibodies helps predict the progression
      to overt hypothyroidism, but it is unclear whether thyroid autoimmunity
      independently affects CHD risk. OBJECTIVE: The objective of the study was to
      compare the CHD risk of subclinical hypothyroidism with and without thyroid
      peroxidase antibodies (TPOAbs). DATA SOURCES AND STUDY SELECTION: A MEDLINE and
      EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting
      baseline thyroid function, antibodies, and CHD outcomes. DATA EXTRACTION:
      Individual data of 38 274 participants from six cohorts for CHD mortality
      followed up for 460 333 person-years and 33 394 participants from four cohorts
      for CHD events. DATA SYNTHESIS: Among 38 274 adults (median age 55 y, 63% women),
      1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive
      TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events.
      Compared with euthyroid individuals, age- and gender-adjusted risks of CHD
      mortality in subclinical hypothyroidism were similar among individuals with and
      without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs
      HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR
      1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of
      CHD mortality and events increased with higher thyrotropin, but within each
      stratum, risks did not differ by TPOAb status. CONCLUSIONS: CHD risk associated
      with subclinical hypothyroidism did not differ by TPOAb status, suggesting that
      biomarkers of thyroid autoimmunity do not add independent prognostic information
      for CHD outcomes.

PMID- 24915120
TI  - Circulating irisin in healthy, young individuals: day-night rhythm, effects of
      food intake and exercise, and associations with gender, physical activity, diet,
      and body composition.
AB  - CONTEXT: The myokine irisin may increase energy expenditure and affect
      metabolism. OBJECTIVE: The objective of the study was to elucidate predictors of
      irisin and study whether circulating irisin may have day-night rhythm in humans.
      DESIGN: This was an observational, cross-sectional study with an additional 24
      hour prospective observational arm (day-night rhythm substudy) and two
      prospective interventional arms (mixed meal substudy and exercise substudy).
      SETTING: The study was conducted at the Hellenic Military School of Medicine
      (Thessaloniki, Greece). PATIENTS AND INTERVENTIONS: One hundred twenty-two
      healthy, young individuals were subjected to anthropometric and body composition
      measurements, and their eating and exercise behavior profiles were assessed with
      validated questionnaires. Subgroups were subjected to day-night rhythm,
      standardized meal ingestion, and 30-minute aerobic exercise studies. MAIN OUTCOME
      MEASURES: Circulating irisin levels were measured. RESULTS: Iotarisin levels were
      lower in males than females (P = .02) after adjustment for lean body mass, which
      was its major determinant. Irisin levels followed a day-night rhythm (P < .001)
      with peak at 9:00 pm. Irisin levels were increased at the end of exercise (84.1
      +/- 10.0 vs 105.8 +/- 14.3 ng/mL; P < .001). Irisin levels were not affected by
      intake of a standardized meal and were not associated with caloric intake or diet
      quality. CONCLUSIONS: In healthy, young individuals, circulating irisin displays
      a day-night rhythm, is correlated with lean body mass, and increases acutely
      after exercise.

PMID- 24915121
TI  - Hypothyroidism is a predictor of disability pension and loss of labor market
      income: a Danish register-based study.
AB  - BACKGROUND: Hypothyroidism is associated with an increased somatic and
      psychiatric disease burden. Whether there are any socioeconomic consequences of
      hypothyroidism, such as early retirement or loss of income, remains unclarified.
      AIM: Our aim was to examine, compared with a matched control group, the risk of
      receiving disability pension (before the age of 60) and the effect on labor
      market income in patients diagnosed with hypothyroidism. METHODS: This was an
      observational register-based cohort study. By record linkage between different
      Danish health registers, 1745 hypothyroid singletons diagnosed before the age of
      60 were each matched with 4 non-hypothyroid controls and followed for a mean of 5
      (range 1-31) years. Additionally, we included 277 same-sex twin pairs discordant
      for hypothyroidism. The risk of disability pension was evaluated by the Cox
      regression analysis. Changes in labor market income progression over 5 years were
      evaluated using a difference in difference model. RESULTS: With a hazard ratio of
      2.24 (95% confidence interval = 1.73-2.89), individuals diagnosed with
      hypothyroidism had a significantly increased risk of disability pension. This
      remained significant when adjusting for educational level and comorbidity (hazard
      ratio = 1.89; 95% confidence interval = 1.42-2.51). In an analysis of labor
      market income, 2 years before compared with 2 years after the diagnosis of
      hypothyroidism, the hypothyroid individuals had on average a ?1605 poorer
      increase than their euthyroid controls (P < .001). Essentially similar results
      were found in the twin population. CONCLUSION: A diagnosis of hypothyroidism
      before the age of 60 is associated with loss of labor market income and an 89%
      increased risk of receiving a disability pension.

PMID- 24915123
TI  - Natural course and survival of neuroendocrine tumors of thymus and lung in MEN1
      patients.
AB  - CONTEXT: The natural course and survival of neuroendocrine tumors (NETs) of
      thymus (Th) and lung in multiple endocrine neoplasia type 1 (MEN1) patients are
      still unknown. OBJECTIVE: Our objective was to assess prevalence, tumor growth,
      and survival of Th and lung NETs in an unselected MEN1 population with long-term
      follow-up. DESIGN: This was an observational study. PATIENTS AND METHODS: A
      longitudinal study was performed using the Dutch national MEN1 database,
      including >90% of the Dutch MEN1 population >16 years of age. Patients under care
      of the Dutch University Medical Centers (1990-2011) (n = 323) were included. MAIN
      OUTCOME MEASURES: The prevalence and survival of Th and lung NETs were assessed.
      Linear mixed-models analysis was applied to assess tumor growth with age as a
      possible confounder and gender, genotype and baseline tumor size as possible
      effect modifiers. RESULTS: Th NETs occurred in 3.4% of patients, almost
      exclusively in males with a 10-year survival of 25% (95% confidence interval = 8%
      80%). A thoracic computed tomography scan was available in 188 patients (58.2%).
      A lung NET was identified in 42 patients (13.0%) with a 10-year survival of 71.1%
      (95% confidence interval = 51%-100%). Tumor volume of lung NETs increased 17% per
      year (P < .001) (tumor doubling time 4.5 years). Tumor doubling time in males was
      2.5 vs 5.5 years in females (P = .05). Lung NET growth was not associated with
      genotype or with baseline tumor size (<1 vs >=1 cm). CONCLUSION: In MEN1
      patients, Th NETs almost exclusively occurred in males and had a very low
      prevalence and a high mortality. Lung NETs occurred more often than previously
      thought, had an indolent course, and occurred equally in both sexes. Tumor growth
      in males was double compared with female patients.

PMID- 24915122
TI  - Genetic evaluation of short stature.
AB  - CONTEXT: Genetics plays a major role in determining an individual's height.
      Although there are many monogenic disorders that lead to perturbations in growth
      and result in short stature, there is still no consensus as to the role that
      genetic diagnostics should play in the evaluation of a child with short stature.
      EVIDENCE ACQUISITION: A search of PubMed was performed, focusing on the genetic
      diagnosis of short stature as well as on specific diagnostic subgroups included
      in this article. Consensus guidelines were reviewed. EVIDENCE SYNTHESIS: There
      are a multitude of rare genetic causes of severe short stature. There is no high
      quality evidence to define the optimal approach to the genetic evaluation of
      short stature. We review genetic etiologies of a number of diagnostic subgroups
      and propose an algorithm for genetic testing based on these subgroups.
      CONCLUSION: Advances in genomic technologies are revolutionizing the diagnostic
      approach to short stature. Endocrinologists must become facile with the use of
      genetic testing in order to identify the various monogenic disorders that present
      with short stature.

PMID- 24915124
TI  - Common genetic variants in the glucocorticoid receptor and the 11beta
      hydroxysteroid dehydrogenase type 1 genes influence long-term cognitive
      impairments in patients with Cushing's syndrome in remission.
AB  - CONTEXT: Cognitive function is impaired in patients with Cushing's syndrome (CS)
      in remission. OBJECTIVE: The objective of the investigation was to study the
      effects of polymorphisms in genes associated with glucocorticoid (GC) sensitivity
      on cognitive function in patients with CS in long-term remission. DESIGN: This
      was a cross-sectional, case-controlled, single-center study. PATIENTS: Fifty
      three patients with CS in remission and 53 controls matched for age, gender, and
      educational level participated in the study. MAIN OUTCOME MEASURES: Cognitive
      function, studied using standardized neuropsychological testing, and
      polymorphisms in the GC receptor (NR3C1; Bcl1 and A3669G), mineralocorticoid
      receptor (NR3C2; I180V), 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1;
      rs11119328), and ATP binding cassette B1 (ABCB1; rs1045642) genes were measured.
      The association between cognitive function and polymorphisms were analyzed using
      linear regression with adjustments for age and educational level. RESULTS: The
      mean age in patients and controls was 53 +/- 14 years. The median (interquartile
      range) duration of remission was 13 (5-18) years. In patients, the single
      nucleotide polymorphism rs11119328 was associated with impairments in processing
      speed, auditory attention, auditory working memory, and reading speed. This
      association was not seen in matched controls. The Bcl1 polymorphism was
      associated with fatigue and worse visual attention and working memory. The
      remaining single-nucleotide polymorphisms were not associated with cognitive
      performance. CONCLUSION: In this study, polymorphisms in the 11betaHSD1 and NR3C1
      genes were associated with impaired cognitive function, indicating that GC
      sensitivity and prereceptor regulation of GC action may play a role in the long
      term consequences of CS. The study provides a novel insight into the etiology of
      cognitive dysfunction in patients with CS in remission.

PMID- 24915125
TI  - Short-term renal support in postoperative repair of tetralogy of Fallot in the
      paediatric intensive care unit: can we predict those who need it?
AB  - INTRODUCTION: Fluid balance and renal function can be difficult to manage in the
      postoperative infant with tetralogy of Fallot. High fluid volumes are often
      needed to maintain cardiac output. Aims To stratify patients at risk for advanced
      renal support following tetralogy of Fallot repair. METHODS: Retrospective
      analysis of all consecutive tetralogy of Fallot cases operated at a single centre
      in a 3-year period. RESULTS: A total of 41 children were identified. All cases
      had loop diuretics administered. Of the cases, 17% required support with a
      peritoneal dialysis catheter, with only one complication of peritoneal dialysis
      catheter blockage. The mean length of paediatric intensive care unit stay in
      those receiving peritoneal dialysis catheter insertion was prolonged by an
      additional mean of 6 days (p<0.001). No statistical significance was found
      between those children requiring peritoneal dialysis and those who did not when
      considering patient age and weight at time of repair, cardiopulmonary bypass and
      aortic cross clamp times, the presence of a transannular patch, or junctional
      ectopic tachycardia. However, volume requirement of more than 35 ml/kg in the
      first 12 hours following repair did increase the likelihood to need peritoneal
      dialysis (p<0.0001). Furthermore, the higher the peak creatinine, the longer the
      stay on intensive care (p<0.01). CONCLUSIONS: Peritoneal dialysis is an effective
      method of dealing with fluid balance in children after tetralogy of Fallot
      repair, with minimal complications. Early consideration should be given to
      peritoneal dialysis when it is clear that high fluid volumes are required
      postoperatively.

PMID- 24915126
TI  - Observation of surface Dirac cone in high-quality ultrathin epitaxial Bi2Se3
      topological insulator on AlN(0001) dielectric.
AB  - Bi2Se3 topological insulators (TIs) are grown on AlN(0001)/Si(111) substrates by
      molecular beam epitaxy. In a one-step growth at optimum temperature of 300 
      degrees C, Bi2Se3 bonds strongly with AlN without forming interfacial reaction
      layers. This produces high epitaxial quality Bi2Se3 single crystals with a
      perfect registry with the substrate and abrupt interfaces, allowing thickness
      scaling down to three quintuple layers (QL) without jeopardizing film quality. It
      is found by angle-resolved photoelectron spectroscopy that, remarkably, Bi2Se3
      films maintain the 3D TI properties at very low thickness of 3QL (~2.88 nm),
      exhibiting top surface gapless metallic states in the form of a Dirac cone. 

PMID- 24915128
TI  - Surface plasmon resonance enhanced real-time photoelectrochemical protein sensing
      by gold nanoparticle-decorated TiO2 nanowires.
AB  - Recently developed photoelectrochemical (PEC) sensing systems represent a unique
      potential detection method for real-time analysis of chemical/biological
      molecules, while the low absorption of TiO2 nanomaterials in the visible
      wavelength region and the slow surface charge transfer efficiency limit the
      ultimate sensitivity. Here we develop a gold nanoparticle-decorated TiO2 nanowire
      sensor for PEC detection of protein binding. The direct attachment of Au
      nanoparticles to TiO2 nanowires offers strong surface plasmon resonance for
      electrochemical field effect amplification, yielding a ~100% increase of
      photocurrent density. In addition, the surface functionalization of gold
      nanoparticles allows for direct capturing of target proteins near the Au/TiO2
      interface and thus substantially enhances the capability of attenuation of energy
      coupling between Au and TiO2, leading to much-improved sensor performance. As a
      proof of concept, cholera toxin subunit B has been robustly detected by the TiO2
      Au nanowire sensor functionalized with ganglioside GM1, with a high sensitivity
      of 0.167 nM and excellent selectivity. Furthermore, the real-time feature of
      photoelectrochemical sensing enables direct measurement of binding kinetics
      between cholera toxin subunit B and GM1, yielding association and disassociation
      rate constants and an equilibrium constant K(d) of 4.17 nM. This surface plasmon
      resonance-enhanced real-time, photoelectrochemical sensing design may lead to
      exciting biodetection capabilities with high sensitivity and real-time kinetic
      studies.

PMID- 24915127
TI  - Precision genome engineering and agriculture: opportunities and regulatory
      challenges.
AB  - Plant agriculture is poised at a technological inflection point. Recent advances
      in genome engineering make it possible to precisely alter DNA sequences in living
      cells, providing unprecedented control over a plant's genetic material. Potential
      future crops derived through genome engineering include those that better
      withstand pests, that have enhanced nutritional value, and that are able to grow
      on marginal lands. In many instances, crops with such traits will be created by
      altering only a few nucleotides among the billions that comprise plant genomes.
      As such, and with the appropriate regulatory structures in place, crops created
      through genome engineering might prove to be more acceptable to the public than
      plants that carry foreign DNA in their genomes. Public perception and the
      performance of the engineered crop varieties will determine the extent to which
      this powerful technology contributes towards securing the world's food supply.

PMID- 24915129
TI  - Production of functional active human growth factors in insects used as living
      biofactories.
AB  - Growth factors (GFs) are naturally signalling proteins, which bind to specific
      receptors on the cell surface. Numerous families of GFs have already been
      identified and remarkable progresses have been made in understanding the pathways
      that these proteins use to activate/regulate the complex signalling network
      involved in cell proliferation or wound healing processes. The bottleneck for a
      wider clinical and commercial application of these factors relay on their
      scalable cost-efficient production as bioactive molecules. The present work
      describes the capacity of Trichoplusia ni insect larvae used as living
      bioreactors in combination with the baculovirus vector expression system to
      produce three fully functional human GFs, the human epidermal growth factor
      (huEGF), the human fibroblast growth factor 2 (huFGF2) and the human keratinocyte
      growth factor 1 (huKGF1). The expression levels obtained per g of insect biomass
      were of 9.1, 2.6 and 3mg for huEGF, huFGF2 and huKGF1, respectively. Attempts to
      increase the productivity of the insect/baculovirus system we have used different
      modifications to optimize their production. Additionally, recombinant proteins
      were expressed fused to different tags to facilitate their purification.
      Interestingly, the expression of huKGF1 was significantly improved when expressed
      fused to the fragment crystallizable region (Fc) of the human antibody IgG. The
      insect-derived recombinant GFs were finally characterized in terms of biological
      activity in keratinocytes and fibroblasts. The present work opens the possibility
      of a cost-efficient and scalable production of these highly valuable molecules in
      a system that favours its wide use in therapeutic or cosmetic applications. 

PMID- 24915130
TI  - In vitro production and purification of isochorismate using a two-enzyme cascade.
AB  - Combining the isochorismate synthase EntC and the chorismatase FkbO in a
      sequential enzyme cascade provides a useful system for the biocatalytic
      production and subsequent purification of isochorismate from an
      isochorismate/chorismate mixture. FkbO has a strict preference for chorismate -
      isochorismate is not accepted as a substrate - therefore the enzyme can be used
      to selectively hydrolyse chorismate, leading to the chiral building block 3,4
      dihydroxycyclohexa-1,5-dienecarboxylate. This simplifies the final purification
      step, as isochorismate is much easier to separate from the chorismate hydrolysis
      products than from chorismate itself. The presented procedure starts with an
      optimised method for purifying chorismate from Escherichia coli culture
      supernatants, which is followed by conversion into isochorismate with the
      isochorismate synthase EntC, removal of the remaining chorismate by FkbO and a
      final purification step using an automated flash chromatography system.
      Isochorismate was isolated in up to 20% yield and >95% purity from chorismate,
      and has been characterised with respect to its degradation and suitability as a
      substrate in enzyme assays. 

PMID- 24915131
TI  - Photosynthetic mixed culture polyhydroxyalkanoate (PHA) production from
      individual and mixed volatile fatty acids (VFAs): substrate preferences and co
      substrate uptake.
AB  - This work studied the effect of the substrate feeding composition on the
      polyhydroxyalkanoate (PHA) accumulation capacity of an acetate enriched
      photosynthetic mixed culture (PMC). From the six tested organic acids - malate,
      citrate, lactate, acetate, propionate and butyrate - only the three volatile
      fatty acids (VFAs) enabled PHA production, with acetate and butyrate leading to
      polyhydroxybutyrate (PHB) formation and propionate leading to a HB:HV copolymer
      with a 51% fraction of hydroxyvalerate (HV). Also, results showed an acceleration
      of butyrate and propionate consumption when fed in the presence of acetate,
      suggesting that the latter can act as a co-substrate for butyrate and propionate
      uptake. Furthermore, results suggest that some PMC bacterial groups present a
      substrate preference for butyrate in relation to acetate and propionate. These
      findings indicate the possibility of feeding the PMC with cheap VFA rich
      fermented wastes, leading to a more cost-effective and environmentally
      sustainable PHA production system. 

PMID- 24915132
TI  - Identification of two regulatory elements controlling Fucosyltransferase 7
      transcription in murine CD4+ T cells.
AB  - Fucosyltransferase VII encoded by the gene Fut7 is essential in CD4(+) T cells
      for the generation of E- and P-selectin ligands (E- and P-lig) which facilitate
      recruitment of lymphocytes into inflamed tissues and into the skin. This study
      aimed to identify regulatory elements controlling the inducible Fut7 expression
      in CD4(+) T cells that occurs upon activation and differentiation of naive T
      cells into effector cells. Comparative analysis of the histone modification
      pattern in non-hematopoetic cells and CD4(+) T cell subsets revealed a
      differential histone modification pattern within the Fut7 locus including a
      conserved non-coding sequence (CNS) identified by cross-species conservation
      comparison suggesting that regulatory elements are confined to this region.
      Cloning of the CNS located about 500 bp upstream of the Fut7 locus, into a
      luciferase reporter vector elicited reporter activity after transfection of the
      alphabeta-WT T cell line, but not after transfection of primary murine CD4(+) Th1
      cells. As quantification of different Fut7 transcripts revealed a predominance of
      transcripts lacking the first exons in primary Th1 cells we searched for an
      alternative promoter. Cloning of an intragenic region spanning a 1kb region
      upstream of exon 4 into an enhancer-containing vector indeed elicited promoter
      activity. Interestingly, also the CNS enhanced activity of this intragenic
      minimal promoter in reporter assays in primary Th1 cells suggesting that both
      elements interact in primary CD4(+) T cells to induce Fut7 transcription.

PMID- 24915133
TI  - Main and accessory olfactory bulbs and their projections in the brain anticipate
      feeding in food-entrained rats.
AB  - The olfactory bulb (OB) has a circadian clock independent of the suprachiasmatic
      nucleus, but very little is known about the functional significance of its
      oscillations. The OB plays a major role in food intake as it contributes to the
      evaluation of the hedonic properties of food, it is necessary for a normal
      pattern of locomotor behavior and their ablation disrupts feeding patterns.
      Previously we demonstrated that OB of rabbit pups can be entrained by periodic
      nursing but it was not clear whether food was the entraining signal. Here we
      hypothesized that OB can be entrained by a food pulse during the day in adult
      rats under a restricted feeding schedule. Then we expect that OB will have a high
      activation before food presentation when animals show food anticipatory activity
      (FAA). To this aim we determined by immunohistochemistry the expression of FOS
      protein, as an indicator of neural activation, in the mitral and granular cell
      layers of the main and accessory OB. Additionally we also explored two of the OB
      brain targets, the piriform cortex (PC) and bed nuclei of the accessory olfactory
      tract (BAOT), in three groups: ad libitum (ALF), restricted feeding (RF), and
      fasted rats after restricted feeding (RF-F). In ALF group FOS levels in both main
      and accessory OB were low during the day and high during the night at the normal
      onset of the increase of activity, in agreement with previous reports. On the
      contrary in RF and RF-F groups FOS was high at the time of FAA, just before food
      presentation, when animals are in a state of high arousal and during food
      consumption but was low during the night. In their brain targets, we observed a
      similar pattern as OB in all groups with the only difference being that FOS
      levels remained high during the night in RF-F group. We conclude that the OB is
      entrained by food restriction by showing high activation at the time of food
      presentation, which persists during fasting and impose a similar FOS pattern to
      the two brain targets explored only in fed animals. 

PMID- 24915134
TI  - Nanobio-based optical sensing and imaging.

PMID- 24915135
TI  - Carbon dioxide insufflation during screening unsedated colonoscopy: a randomised
      clinical trial.
AB  - One of the methods used to reduce pain and discomfort during colonoscopy is
      insufflation of carbon dioxide instead of air. However, the actual benefit of
      carbon dioxide insufflation is not unequivocally proven. The aim of the study was
      to evaluate the advantages of carbon dioxide insufflation during screening
      colonoscopy. A total of 200 patients undergoing screening colonoscopy between
      2010 and 2011 were included in the prospective, randomized study carried out in a
      surgical referral center. Screening unsedated colonoscopy with either air or
      carbon dioxide insufflation was performed; patients were randomly assigned to air
      or carbon dioxide group by means of computer-generated randomization lists. All
      examinations were performed in an ambulatory setting with standard
      videocolonoscopes. The main outcomes analyzed were (a) duration of the entire
      procedure, (b) cecal intubation time, and (c) pain severity immediately, 15, and
      60 min after the procedure. Group I included 59 women and 41 men and group II
      included 51 women and 49 men. The duration of the procedure was circa 10 min in
      both groups. Pain score values immediately and 15 min after the procedure were
      similar in both groups (P=0.624 and 0.305, respectively). A lower pain score was
      observed only after 60 min in patients insufflated with carbon dioxide (1.28 vs.
      1.54, P=0.008). No pain reduction was observed in women and in obese patients
      (BMI>30). Carbon dioxide insufflation during unsedated screening colonoscopy does
      not decrease the duration of the procedure and appears to reduce pain intensity
      at 60 min after examination to an extent without clinical significance. The study
      was registered at ClinicalTrials.gov, number NCT01461564.

PMID- 24915136
TI  - Haplotype-habitat associations of Coptotermes gestroi (Termitoidae:
      Rhinotermitidae) from mitochondrial DNA genes.
AB  - Coptotermes gestroi (Wasmann) or the Asian subterranean termite is a serious
      structural pest in urban settlements in Southeast Asia that has been introduced
      to other parts of the world through human commerce. Although mitochondrial DNA
      markers were previously used to shed light on the dispersal history of the Asian
      subterranean termite, there were limited attempts to analyze or include
      populations of the termite found in the wild in Southeast Asia. In this study, we
      analyzed the 16S ribosomal RNA (16S rRNA) and cytochrome c oxidase subunit 1
      (cox1) genes of Asian subterranean termite colonies found in mangrove swamps,
      beach forests, plantations, and buildings in semi-urban and urban areas to
      determine the relationship between colonies found in the wild and the urban
      habitat, and to investigate the possibility of different ecotypes of the termite
      in Peninsular Malaysia. Our findings show that the 16S rRNA haplotypes recovered
      from this study clustered into eastern, western, and southern populations of the
      termite, while the cox1 haplotypes were often specific to an area or site. The
      16S rRNA and cox1 genes or haplotypes showed that the most abundant haplotype
      occupied a wide range of environments or habitats. In addition, the cox1 tree
      showed evidence of historical biogeography where basal haplotypes inhabited a
      wide range of habitats, while apical haplotypes were restricted to mangrove
      swamps and beach forests. Information on the haplotype-habitat association of C.
      gestroi will enable the prediction of habitats that may harbor or be at risk of
      invasion in areas where they have been introduced. 

PMID- 24915137
TI  - Dietary exposure in utero and during lactation to a mixture of genistein and an
      anti-androgen fungicide in a rat mammary carcinogenesis model.
AB  - Endocrine disruptors may play substantial roles in the high incidence of breast
      cancer. We previously described how early exposure to the mixture of
      phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects
      peripubertal mammary development. This study evaluates the carcinogenic potential
      of exposure to V alone or associated with G from conception until weaning in
      Wistar rats. Dams were exposed to V, G or GV during pregnancy/lactation. At PND50
      offspring were treated with DMBA[7,12-dimethylbenz(a)anthracene]. V or GV
      maternal exposure decreased number of DMBA-induced mammary tumors in the
      offspring, without significant modifications in tumor incidence, multiplicity and
      latency. G exposure decreased number of tumors, incidence and multiplicity.
      Unexpectedly, GV exposure increased tumor volume (p=0.04 vs controls) and
      epithelial proliferation (p=0.001 vs controls; p=0.005 vs G,V only). All tumors
      were in situ carcinomas. Concluding, maternal gestation/lactation exposure to a
      vinclozolin and genistein mixture significantly increases offspring tumor growth
      without changes in carcinogenesis susceptibility. 

PMID- 24915138
TI  - Activation of ER stress by hydrogen peroxide in C2C12 myotubes.
AB  - The purpose of this study was to examine the link between oxidative stress and
      endoplasmic reticulum (ER) stress in myogenic cells. C2C12 myotubes were
      incubated with hydrogen peroxide (H2O2, 200 MUM) and harvested 4h or 17 h after
      the induction of this oxidative stress. A massive upregulation of binding
      immunoglobulin protein (BiP) was found, indicating the presence of ER stress.
      Nevertheless, the three branches of the unfolded protein response (UPR) were not
      activated to the same extent. The double-stranded RNA-dependent protein kinase
      (PKR)-like ER kinase (PERK) branch was the most activated as shown by the
      increase of phospho-eukaryotic translation-initiation factor 2alpha (eIF2alpha,
      Ser51) and the mRNA levels of activating transcription factor 4 (ATF4), C/EBP
      homologous (CHOP) and tribbles homolog 3 (TRB3). The slight increase in the
      spliced form of X-box binding protein 1 (XBP1s) together with the decrease of the
      unspliced form (XBP1u) indicated a higher endoribonuclease activity of inositol
      requiring 1alpha (IRE1alpha). The transcriptional activity of activating
      transcription factor 6 (ATF6) remained unchanged after incubation with H2O2. The
      mechanisms by which the three branches of UPR can be specifically regulated by
      oxidative stress are currently unresolved and need further investigations.

PMID- 24915139
TI  - Tuning excited states of bipyridyl platinum(II) chromophores with pi-bonded
      catecholate organometallic ligands: synthesis, structures, TD-DFT calculations,
      and photophysical properties.
AB  - A series of bipyridyl (bpy) Pt(II) complexes with pi-bonded catecholate (cat)
      [(bpy)Pt(LM)][BF4]n (2-5) (LM = Cp*Rh(cat), n = 2; Cp*Ir(cat), n = 2; Cp*Ru(cat),
      n = 1; and (C6H6)Ru(cat), n = 2) were prepared and fully characterized. The
      molecular structures of the four compounds were determined and showed that the
      solid-state packing is different and dependent on the pi-bonded catecholate unit.
      For instance, while the (bpy)Pt(II) complexes 2 and 3 with rhodium and iridium
      catecholates did not show any Pt...Pt interactions those with the ruthenium
      catecholates 4 and 5 showed the presence of Pt...Pt and pi-pi interactions among
      individual units and generated one- and two-dimensional supramolecular chains.
      The photophysical properties of these compounds 2-5 were investigated and showed
      that all compounds are luminescent at low temperature, in contrast to the well
      known parent compound [(C6H4O2)Pt(bpy)] (1), which is weakly luminescent at 77 K.
      Time-dependent density functional theory studies are advanced to explain this
      difference in behavior and to highlight the role of the pi-bonded catecholate
      system. 

PMID- 24915140
TI  - A thienoisoindigo-naphthalene polymer with ultrahigh mobility of 14.4 cm(2)/V.s
      that substantially exceeds benchmark values for amorphous silicon semiconductors.
AB  - By considering the qualitative benefits associated with solution rheology and
      mechanical properties of polymer semiconductors, it is expected that polymer
      based electronic devices will soon enter our daily lives as indispensable
      elements in a myriad of flexible and ultra low-cost flat panel displays. Despite
      more than a decade of research focused on designing and synthesizing state-of-the
      art polymer semiconductors for improving charge transport characteristics, the
      current mobility values are still not sufficient for many practical applications.
      The confident mobility in excess of ~10 cm(2)/V.s is the most important
      requirement for enabling the realization of the aforementioned near-future
      products. We report on an easily attainable donor-acceptor (D-A) polymer
      semiconductor: poly(thienoisoindigo-alt-naphthalene) (PTIIG-Np). An unprecedented
      mobility of 14.4 cm(2)/V.s, by using PTIIG-Np with a high-k gate dielectric
      poly(vinylidenefluoride-trifluoroethylene) (P(VDF-TrFE)), is achieved from a
      simple coating processing, which is of a magnitude that is very difficult to
      obtain with conventional TFTs by means of molecular engineering. This work,
      therefore, represents a major step toward truly viable plastic electronics. 

PMID- 24915142
TI  - Palladium-catalyzed ortho-alkoxylation of 2-aryl-1,2,3-triazoles.
AB  - Palladium-catalyzed alkoxylation of 2-aryl-1,2,3-triazoles was described in the
      presence of various groups in the aromatic rings. In addition, some other
      directing groups of heterocycles containing nitrogen were explored. 

PMID- 24915141
TI  - Characterization of the floral transcriptome of Moso bamboo (Phyllostachys
      edulis) at different flowering developmental stages by transcriptome sequencing
      and RNA-seq analysis.
AB  - BACKGROUND: As an arborescent and perennial plant, Moso bamboo (Phyllostachys
      edulis (Carriere) J. Houzeau, synonym Phyllostachys heterocycla Carriere) is
      characterized by its infrequent sexual reproduction with flowering intervals
      ranging from several to more than a hundred years. However, little bamboo genomic
      research has been conducted on this due to a variety of reasons. Here, for the
      first time, we investigated the transcriptome of developing flowers in Moso
      bamboo by using high-throughput Illumina GAII sequencing and mapping short reads
      to the Moso bamboo genome and reference genes. We performed RNA-seq analysis on
      four important stages of flower development, and obtained extensive gene and
      transcript abundance data for the floral transcriptome of this key bamboo
      species. RESULTS: We constructed a cDNA library using equal amounts of RNA from
      Moso bamboo leaf samples from non-flowering plants (CK) and mixed flower samples
      (F) of four flower development stages. We generated more than 67 million reads
      from each of the CK and F samples. About 70% of the reads could be uniquely
      mapped to the Moso bamboo genome and the reference genes. Genes detected at each
      stage were categorized to putative functional categories based on their
      expression patterns. The analysis of RNA-seq data of bamboo flowering tissues at
      different developmental stages reveals key gene expression properties during the
      flower development of bamboo. CONCLUSION: We showed that a combination of
      transcriptome sequencing and RNA-seq analysis was a powerful approach to
      identifying candidate genes related to floral transition and flower development
      in bamboo species. The results give a better insight into the mechanisms of Moso
      bamboo flowering and ageing. This transcriptomic data also provides an important
      gene resource for improving breeding for Moso bamboo.

PMID- 24915144
TI  - Somatic mutations in 33 benign and malignant hot thyroid nodules in children and
      adolescents.
AB  - Hot thyroid nodules (HTNs) in children are rare. Their reported malignancy rate
      is higher than in adults. However molecular data are rare. We present clinical
      and molecular data for 33 consecutive (29 benign and 4 malignant) HTNs. 17/29
      Benign HTNs (59%) harbored somatic TSHR mutations. The most commonly observed
      mutation was M453T (in 8/29 samples). T632I and D633Y mutations were each
      detected twice. All other TSHR mutations were each found in one sample, including
      the new A538T mutation. One NRAS mutation was detected in a benign HTN with a
      M453T mutation. A PAX8/PPARG rearrangement was found in one malignant HTN. A
      T632I mutation was detected in one hot papillary thyroid carcinoma. The
      percentage of TSHR mutation positive HTNs in children and adolescents is within
      the range observed in adults. Contrary to adults, the M453T mutation is the
      predominant TSHR mutation in HTNs of children and adolescents. The increased
      malignancy rate of HTNs of children does not appear to be associated with RAS,
      BRAF, PAX8/PPARG and RET/PTC mutations.

PMID- 24915143
TI  - PharmGKB summary: uric acid-lowering drugs pathway, pharmacodynamics.

PMID- 24915145
TI  - Separate class true discovery rate degree of association sets for biomarker
      identification.
AB  - In 2008, Efron showed that biological features in a high-dimensional study can be
      divided into classes and a separate false discovery rate (FDR) analysis can be
      conducted in each class using information from the entire set of features to
      assess the FDR within each class. We apply this separate class approach to true
      discovery rate degree of association (TDRDA) set analysis, which is used in
      clinical-genomic studies to identify sets of biomarkers having strong association
      with clinical outcome or state while controlling the FDR. Careful choice of
      classes based on prior information can increase the identification power of the
      separate class analysis relative to the overall analysis. 

PMID- 24915147
TI  - Accumulation of BDCA1+ dendritic cells in interstitial fibrotic lung diseases and
      Th2-high asthma.
AB  - Dendritic cells (DCs) significantly contribute to the pathology of several mouse
      lung disease models. However, little is known of the contribution of DCs to human
      lung diseases. In this study, we examined infiltration with BDCA1+ DCs of human
      lungs in patients with interstitial lung diseases or asthma. Using flow
      cytometry, we found that these DCs increased by 5~6 fold in the lungs of patients
      with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are
      both characterized by extensive fibrosis in parenchyma. The same DC subset also
      significantly increased in the lung parenchyma of patients with chronic
      obstructive pulmonary disease, although the degree of increase was relatively
      modest. By employing immunofluorescence microscopy using FcepsilonRI and MHCII as
      the specific markers for BDCA1+ DCs, we found that the numbers of BDCA1+ DCs also
      significantly increased in the airway epithelium of Th2 inflammation-associated
      asthma. These findings suggest a potential contribution of BDCA1+ DCs in human
      lung diseases associated with interstitial fibrosis or Th2 airway inflammation.

PMID- 24915148
TI  - A feasibility study of an improved procedure for using EEG to detect brain
      responses to imagery instruction in patients with disorders of consciousness.
AB  - One of the major concerns of recent studies is the correct discrimination between
      vegetative and minimally conscious state as the distinction between these two
      conditions has major implications for subsequent patient rehabilitation. In
      particular, it would be advantageous to establish communication with these
      patients. This work describes a procedure using EEG to detect brain responses to
      imagery instruction in patients with disorders of consciousness. Five healthy
      subjects and five patients with different disorders of consciousness took part in
      the study. A support vector machine classifier applied to EEG data was used to
      distinguish two mental tasks (Imagery Trial) and to detect answers to simple yes
      or no questions (pre-Communication Trial). The proposed procedure uses feature
      selection based on a nested-leave-one-out algorithm to reduce the number of
      electrodes required. We obtained a mean classification accuracy of 82.0% (SD
      5.1%) for healthy subjects and 84.6% (SD 9.1%) for patients in the Imagery Trial,
      and a mean classification accuracy of 80.7% (SD 11.5%) for healthy subjects and
      91.7% (SD 7.4%) for patients in the pre-Communication Trial. The subset of
      electrodes selected was subject and session dependent. 

PMID- 24915146
TI  - Urinary and plasma levels of vasohibin-1 can predict renal functional
      deterioration in patients with renal disorders.
AB  - Vasohibin-1 (VASH-1) is a negative feedback regulator of angiogenesis, and a
      small vasohibin-binding protein (SVBP) serves as its secretory chaperone and
      contributes to its antiangiogenic effects. In the present study, we aimed to
      define the clinical significance of VASH-1 and SVBP in patients with chronic
      kidney disease (CKD). We recruited 67 Japanese hospitalized patients with renal
      disorders with (n = 45) or without (n = 22) renal biopsy samples and 10 Japanese
      healthy controls. We evaluated the correlations between the plasma and urinary
      levels of VASH-1/VASH-1-SVBP complex/SVBP and the clinicopathological parameters.
      The plasma levels of VASH-1 were inversely correlated with age and systolic and
      diastolic blood pressure and positively correlated with crescent formation.
      Increased plasma and urinary levels of VASH-1 and VASH-1-SVBP complex were
      significantly correlated with worse renal outcomes. These results demonstrate an
      association between elevated urinary and plasma levels of VASH-1 and progressive
      decline of the renal function, thus suggesting a potential role for VASH-1 in
      predicting a worse renal prognosis in patients with renal disease, including CKD.

PMID- 24915150
TI  - [Ureteroscopy: is it the best?].
AB  - Over the last 40 years the treatment of urolithiasis passed from open surgical
      therapies to minimally invasive approaches. From the introduction of the first
      ureteroscopes in '80s many technological improvements allowed to reduce
      endourological instruments' size, ensuring in the meanwhile an increasingly high
      success rate in the resolution of the urolithiasis. The purpose of the study is
      to review the current role of the ureteroscopy(URS) in the treatment of urinary
      stones. A non-systematic review was performed considering the most recent
      Guidelines and results from Literature. The results confirm that, considering
      ureteral calculi, the stone-free rate (SFR) for URS is significantly higher than
      for ESWL in the treatment of distal ureteral stones <10 mm and >10 mm. Endoscopy
      has a first-line role also in the treatment of proximal ureteral stones >10 mm,
      together with ESWL. Retreatment rate and ancillary procedures are also lower in
      patients treated with URS, despite it is more invasive if compared with ESWL.
      Recent data are available in Literature about the treatment of nephrolithiasis
      with Retrograde Intra-Renal Surgery (RIRS). RIRS is the first-line treatment,
      together with ESWL, for stones <20 mm, and second choice for stones >20 mm.
      However, for large renal stones the role of RIRS is still being discussed. In
      conclusion, the majority of urinary stones can be treated by rigid or flexible
      URS. Further studies are required to clarify the role of endoscopy in the
      treatment of large stones, especially if compared to percutaneous approaches.

PMID- 24915149
TI  - [Prevention of nephrolithiasis: a review].
AB  - Nephrolithiasis is a very common condition, with a prevalence of about 8% in the
      general population. Genetic as well as environmental factors are thought to
      contribute to its pathogenesis. Environmental and especially dietary factors are
      important in primary as well as in secondary prevention. We review the relevant
      literature of factors associated with an increased risk of stones that might be
      object of medical prevention for nephrolithiasis. 

PMID- 24915151
TI  - [PCNL: what's changed?].
AB  - PCNL is a endourological technique for the treatment of kidney stones disease.
      It's aim is to achieve the complete clearance via a percutaneous access. This
      technique, as we know it today, was developed by Johanson and Fernstrom in 1976
      who used the technological advances in percutaneous fluoroscopy to get the
      percutaneous access. Following the application of various sources of energy for
      the fragmentation of the calculi such as ultrasound energy, there was the
      worldwide diffusion of PCNL thanks to Alken and Marbergen in Europe, Segura and
      Clayman in the USA. Despite in the early '80s the PCNL lost the initial impulse
      in favor of the SWL, in the '90s, it revived a second golden age through the
      application of emerging technologies such as computed tomography, techniques of
      obtaining the percutaneous access, flexible instrumentation, laser energy and,
      more recently, robotic surgery, and virtual reality. All of these contributed to
      bring the PCNL on the road up of the mini-invasiveness to the latest development
      of Microperc. The Microperc allows the treatment of stones of 2 cm in diameter
      also, obtaining the access under ultrasound, fluoroscopic and direct vision
      guidance. A complete system including micor-optics, laser fiber and irrigation
      system is then inserted into the same needle with a diameter of 4.85, 8 or 10 Fr
      The CROES used logistic developments by creating a global network and a multi
      center database. The PCNL study, concluded in 2009, has led to the publication of
      as many as 27 scientific papers on this subject. 

PMID- 24915152
TI  - Agonist-induced beta2-adrenoceptor desensitization and downregulation enhance pro
      inflammatory cytokine release in human bronchial epithelial cells.
AB  - It is not clear whether increased asthma severity associated with long-term use
      of beta2-adrenoceptor (beta2-AR) agonists can be attributed to receptor
      degradation and increased inflammation. We investigated the cross-talk between
      beta-AR agonist-mediated effects on beta2-AR function and expression and cytokine
      release in human bronchial epithelial cells. In 16HBE14o(-) cells grown in the
      presence and absence of beta-AR agonists and/or antagonists, the beta2-AR density
      was assessed by radioligand binding; the receptor protein and mRNA was determined
      using laser scanning cytometer and RT-PCR; cAMP generation, the cytokines IL-6
      and IL-8 release were determined using AlphaScreen Assay and ELISA, respectively.
      Isoprenaline (ISO) and salbutamol (Salbu) induced a concentration- and time
      dependent significant decrease in beta2-AR density. Both Salbu and ISO reduced
      cAMP generation in a concentration-dependent manner while in same cell culture
      the IL-6 and IL-8 release was significantly enhanced. These effects were
      antagonized to a greater extent by ICI 118.551 than by propranolol, but CGP
      20712A had no effect. Reduction of the beta2-AR protein and mRNA could be seen
      when cells were treated with ISO for 24 h. Our findings indicate a direct link
      between cytokine release and altered beta2-AR expression and function in airway
      epithelial cells. beta2-AR desensitization and downregulation induced by long
      term treatment with beta2-AR agonists during asthma may account for adverse
      reactions also due to enhanced release of pro-inflammatory mediators and should,
      thus, be considered in asthma therapy. 

PMID- 24915155
TI  - Programming fluid transport in paper-based microfluidic devices using razor
      crafted open channels.
AB  - Manipulating fluid transport in microfluidic, paper-based analytical devices
      (MUPADs) is an essential prerequisite to enable multiple timed analytical steps
      on the same device. Current methods to control fluid distribution mainly rely on
      controlling how slowly the fluid moves within a device or by activating an on/off
      switch to flow. In this Article, we present an easy approach for programming
      fluid transport within paper-based devices that enables both acceleration as well
      as delay of fluid transport without active pumping. Both operations are
      programmed by carving open channels either longitudinally or perpendicularly to
      the flow path using a craft-cutting tool equipped with a knife blade. Channels
      are crafted after MUPADs fabrication enabling the end user to generate patterns
      of open-channels on demand by carving the porous material of the paper without
      cutting or removing the paper substrate altogether. Parameters to control the
      acceleration or delay of flow include the orientation, length, and number of open
      channels. Using this method, accelerated as well as reduced fluid transport rates
      were achieved on the same device. This methodology was applied to MUPADs for
      multiple and time-programmable assays for metal ion determination. 

PMID- 24915154
TI  - Ligand-based photooxidations of dithiomaltolato complexes of Ru(II) and Zn(II):
      photolytic CH activation and evidence of singlet oxygen generation and quenching.
AB  - The complex [Ru(bpy)2(ttma)](+) (bpy = 2,2'-bipyridine; ttma = 3-hydroxy-2-methyl
      thiopyran-4-thionate, 1, has previously been shown to undergo an unusual C-H
      activation of the dithiomaltolato ligand upon outer-sphere oxidation. The
      reaction generated alcohol and aldehyde products 2 and 3 from C-H oxidation of
      the pendant methyl group. In this report, we demonstrate that the same products
      are formed upon photolysis of 1 in presence of mild oxidants such as methyl
      viologen, [Ru(NH3)6](3+) and [Co(NH3)5Cl](2+), which do not oxidize 1 in the
      dark. This reactivity is engendered only upon excitation into an absorption band
      attributed to the ttma ligand. Analogous experiments with the homoleptic
      Zn(ttma)2, 4, also result in reduction of electron acceptors upon excitation of
      the ttma absorption band. Complexes 1 and 4 exhibit short-lived visible
      fluorescence and long-lived near-infrared phosphorescence bands. Singlet oxygen
      is both generated and quenched during aerobic excitation of 1 or 4, but is not
      involved in the C-H activation process. 

PMID- 24915153
TI  - Role of intron-mediated enhancement on accumulation of an Arabidopsis NB-LRR
      class R-protein that confers resistance to Cucumber mosaic virus.
AB  - The accumulation of RCY1 protein, which is encoded by RESISTANCE TO CMV(Y)
      (RCY1), a CC-NB-LRR class R-gene, is tightly correlated with the strength of the
      resistance to a yellow strain of Cucumber mosaic virus [CMV(Y)] in Arabidopsis
      thaliana. In order to enhance resistance to CMV by overexpression of RCY1, A.
      thaliana was transformed with intron-less RCY1 cDNA construct under the control
      of strong CaMV35S promoter. Remarkably, a relative amount of RCY1 protein
      accumulation in the transformants was much lower than that in plants expressing
      genomic RCY1 under the control of its native promoter. To identify a regulatory
      element of RCY1 that could cause such differential levels of RCY1 accumulation, a
      series of RCY1 cDNA and genomic RCY1 constructs were transiently expressed in
      Nicotiana benthamiana leaves by the Agrobacterium-mediated infiltration method.
      Comparative analysis of the level of RCY1 accumulation in the leaf tissues
      transiently expressing each construct indicated that the intron located in the
      RCY1-coding region of genomic RCY1, but not the native RCY1 genomic promoter or
      the 5'-and 3'-untranslated regions of RCY1, was indispensable for high level RCY1
      accumulation. The increased levels of RCY1 accelerated plant disease defense
      reactions. Interestingly, such intron-mediated enhancement of RCY1 accumulation
      depended neither on the abundance of the RCY1 transcript nor on the RCY1 specific
      intron sequence. Taken together, intron-mediated RCY1 expression seems to play a
      key role in the expression of complete resistance to CMV(Y) by maintaining RCY1
      accumulation at high levels. 

PMID- 24915156
TI  - Consensus scoring approach to identify the inhibitors of AMP-activated protein
      kinase alpha2 with virtual screening.
AB  - Due to the involvement in the ischemic damage in the brain, 5'-adenosine
      monophosphate-activated protein kinase subunit alpha2 (AMPK2) serves as a
      promising target for the development of new medicines for stroke. Despite such a
      pharmaceutical importance, only a few small-molecule inhibitors have been
      reported so far. We aim in this study to identify a new class of AMPK2 inhibitors
      based on the structure-based virtual screening with docking simulations. To take
      advantage of and supplement the deficiencies of force field-based and empirical
      scoring functions, a consensus scoring method is employed to select the putative
      inhibitors by the combined use of AutoDock and FlexX programs. Prior to the
      virtual screening with docking simulations, both scoring functions are modified
      by implementing the molecular solvation free energy term to enhance the accuracy
      in estimating the protein-ligand binding affinity. As a consequence of the
      consensus virtual screening with the two modified scoring functions, we find
      seven structurally diverse AMPK2 inhibitors with micromolar inhibitory activity.
      Detailed binding mode analyses indicate that all these inhibitors can be
      stabilized in the ATP-binding pocket through the simultaneous establishment of
      the multiple hydrogen bonds and hydrophobic interactions. It is also found that a
      high inhibitory activity can be achieved by the reduction of desolvation cost for
      the inhibitor as well as by the strengthening of the enzyme-inhibitor
      interactions. Thus, the results of the present study demonstrate the
      outperformance of consensus scoring with the force field-based and empirical
      scoring functions that are modified to include the effects of ligand solvation on
      protein-ligand docking. 

PMID- 24915157
TI  - Treatment pattern of type 2 diabetes differs in two German regions and with
      patients' socioeconomic position.
AB  - BACKGROUND: Diabetes treatment may differ by region and patients' socioeconomic
      position. This may be particularly true for newer drugs. However, data are highly
      limited. METHODS: We examined pooled individual data of two population-based
      German studies, KORA F4 (Cooperative Health Research in the Region of Augsburg,
      south), and the HNR (Heinz Nixdorf Recall study, west) both carried out 2006 to
      2008. To ascertain the association between region and educational level with anti
      hyperglycemic medication we fitted poisson regression models with robust error
      variance for any and newer anti-hyperglycemic medication, adjusting for age, sex,
      diabetes duration, BMI, cardiovascular disease, lifestyle, and insurance status.
      RESULTS: The examined sample comprised 662 participants with self-reported type 2
      diabetes (KORA F4: 83 women, 111 men; HNR: 183 women, 285 men). The probability
      to receive any anti-hyperglycemic drug as well as to be treated with newer anti
      hyperglycemic drugs such as insulin analogues, thiazolidinediones, or glinides
      was significantly increased in southern compared to western Germany (prevalence
      ratio (PR); 95% CI: 1.12; 1.02-1.22, 1.52;1.10-2.11 respectively). Individuals
      with lower educational level tended to receive anti-hyperglycemic drugs more
      likely than their better educated counterparts (PR; 95% CI univariable: 1.10;
      0.99-1.22; fully adjusted: 1.10; 0.98-1.23). In contrast, lower education was
      associated with a lower estimated probability to receive newer drugs among those
      with any anti-hyperglycemic drugs (PR low vs. high education: 0.66; 0.48-0.91;
      fully adjusted: 0.68; 0.47-0.996). CONCLUSIONS: We found regional and individual
      social disparities in overall and newer anti-hyperglycemic medication which were
      not explained by other confounders. Further research is needed.

PMID- 24915159
TI  - Brain metabolic crisis in traumatic brain injury: what does it mean?

PMID- 24915158
TI  - Intestinal cell barrier function in vitro is severely compromised by keratin 8
      and 18 mutations identified in patients with inflammatory bowel disease.
AB  - Keratin 8 and 18 (K8/K18) mutations have been implicated in the aetiology of
      certain pathogenic processes of the liver and pancreas. While some K8 mutations
      (K8 G62C, K8 K464N) are also presumed susceptibility factors for inflammatory
      bowel disease (IBD), the only K18 mutation (K18 S230T) discovered so far in an
      IBD patient is thought to be a polymorphism. The aim of our study was to
      demonstrate that these mutations might also directly affect intestinal cell
      barrier function. Cell monolayers of genetically engineered human colonocytes
      expressing these mutations were tested for permeability, growth rate and
      resistance to heat-stress. We also calculated the change in dissociation constant
      (Kd, measure of affinity) each of these mutations introduces into the keratin
      protein, and present the first model of a keratin dimer L12 region with in silico
      clues to how the K18 S230T mutation may affect keratin function. Physiologically,
      these mutations cause up to 30% increase in paracellular permeability in vitro.
      Heat-stress induces little keratin clumping but instead cell monolayers peel off
      the surface suggesting a problem with cell junctions. K18 S230T has pronounced
      pathological effects in vitro marked by high Kd, low growth rate and increased
      permeability. The latter may be due to the altered distribution of tight junction
      components claudin-4 and ZO-1. This is the first time intestinal cells have been
      suggested also functionally impaired by K8/K18 mutations. Although an in vitro
      colonocyte model system does not completely mimic the epithelial lining of the
      intestine, nevertheless the data suggest that K8/K18 mutations may be also able
      to produce a phenotype in vivo. 

PMID- 24915160
TI  - Exploring structural trends for complexes of Me2E(OSO2CF3)2 (E = Si, Ge, Sn) with
      pyridine derivatives.
AB  - The coordination of Me2E(OTf)2 (E = Si, Ge, Sn) acceptors by dmap or 2,2'-bipy
      furnishes two series of complexes which exhibit distinct structural trends that
      correlate with the covalent radii of the tetrael elements, and which contrast
      complexes of these ligands with EX4 (X = Cl or Br). 

PMID- 24915162
TI  - Pseudohypoparathyroidism with Hashimoto's thyroiditis and Turner syndrome: a case
      report.
AB  - OBJECTIVE: To report the case of an individual with PHP, Turner syndrome and
      Hashimoto's thyroiditis. CASE: A 16-year-old girl was referred to our hospital
      with chief complaint of short stature. She presented with round chubby facies,
      short neck, obesity and short stature. Radiography indicated short metatarsals
      and metacarpals, which mainly affected the second, third and fourth digits.
      Biochemistry revealed hyperphosphatemia, increased serum concentrations of
      parathyroid hormone and thyroid stimulating hormone, elevated levels of
      follicular-stimulating hormone and prolactin, and increased thyroid peroxidase
      antibody and thyroglobulin antibody. Radiographic examination revealed delayed
      bone age and pelvic ultrasonography demonstrated an immature uterus. Karyotype
      analysis showed 46,X,i(Xq10), while molecular analysis revealed a same sense
      mutation in exon 5 of GNAS (ATC -> ATT, Ile).The specific diagnosis was made of
      Turner syndrome in the presence of Hashimoto's thyroiditis and PHP. She was
      treated with calcium supplementation, calcitriol and thyroxine. CONCLUSIONS: This
      is the first case report to describe a combination of Turner syndrome with these
      other clinical entities, and their co-existence should be considered and further
      investigated.

PMID- 24915163
TI  - Is there any relationship between cardiovascular risk markers and young women
      with diminished ovarian reserve?
AB  - OBJECTIVE: It has been widely known that cardiovascular disease (CVD) risk is
      increased in menopause. The aim of the study was to evaluate whether this risk
      was elevated in young women with diminished ovarian reserve (DOR). METHODS: A
      hundred women with DOR and 100 women with normal ovarian reserve (NOR) attending
      the infertility unit at Suleymaniye Maternity, Research &Training Hospital, were
      enrolled in the study. CVD risk markers such as insulin resistance (defined by
      the homeostasis model assessment ratio [HOMA-IR]), C-reactive protein (CRP), low
      density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol
      (TC), and triglyceride (TG) were assessed. RESULTS: HOMA-IR, CRP, TG, LDL levels
      were higher and HDL was lower among patients with DOR compared to the controls (p
      < 0.05 for all). There were positive associations between DOR and HOMA-IR, CRP,
      TG, LDL levels and a negative correlation with HDL (p < 0.05 for all). However,
      multivariate logistic regression analysis showed that HOMA-IR, CRP, TG, and HDL
      were independent variables that were associated with DOR. CONCLUSIONS: CVD risk
      markers were increased in women with DOR. Further studies with larger groups are
      needed to investigate the nature of the link in these patients.

PMID- 24915161
TI  - Generation of three-dimensional retinal tissue with functional photoreceptors
      from human iPSCs.
AB  - Many forms of blindness result from the dysfunction or loss of retinal
      photoreceptors. Induced pluripotent stem cells (iPSCs) hold great potential for
      the modelling of these diseases or as potential therapeutic agents. However, to
      fulfill this promise, a remaining challenge is to induce human iPSC to recreate
      in vitro key structural and functional features of the native retina, in
      particular the presence of photoreceptors with outer-segment discs and light
      sensitivity. Here we report that hiPSC can, in a highly autonomous manner,
      recapitulate spatiotemporally each of the main steps of retinal development
      observed in vivo and form three-dimensional retinal cups that contain all major
      retinal cell types arranged in their proper layers. Moreover, the photoreceptors
      in our hiPSC-derived retinal tissue achieve advanced maturation, showing the
      beginning of outer-segment disc formation and photosensitivity. This success
      brings us one step closer to the anticipated use of hiPSC for disease modelling
      and open possibilities for future therapies. 

PMID- 24915167
TI  - Reused cyclodextrin as a new way to deliver and enhance drug loading onto ion
      exchange resin.
AB  - Abstract Context: Cyclodextrins could improve drug solubility and drug loading
      onto ion exchange resins. Moreover, the remaining cyclodextrin in the solution
      might be reused for drug solubility enhancement and drug loading onto resin.
      Objectives: To investigate the application of fresh and reused cyclodextrin to
      improve drug solubility and drug loading onto resin. Methods: The inclusion
      complexes were prepared and characterized using beta-cyclodextrin (betaCD) and 2
      hydroxypropyl-beta-cyclodextrin (HPbetaCD). The drug solution was loaded onto
      resin with and without cyclodextrin. Then, the remaining cyclodextrin was reused
      for the complex and the drug loading process. Results and discussion: Improved
      drug solubility was observed when using cyclodextrins. The complex was
      successfully formed with 1:1 stoichiometry. The increase in drug solubility with
      cyclodextrins improved drug loading onto resin. The cyclodextrins delivered drug
      to bind with resin, forming resinate, and did not bind with the resinate
      themselves, which was confirmed by quantification of the amount of cyclodextrin
      in drug loading solution before and after drug loading process. Therefore,
      cyclodextrins were available to reuse for drug loading without affecting the
      percentage of drug loading. Conclusions: Reused cyclodextrin is a novel way to
      deliver and enhance drug loading onto resin for development of an ion exchange
      based drug delivery system.

PMID- 24915164
TI  - Fungal exposure, atopy, and asthma exacerbations in Puerto Rican children.
AB  - BACKGROUND: Glucan is a component of the fungal cell wall that is used as a
      marker of fungal exposure. Little is known about indoor glucan, atopy, and asthma
      exacerbations among children living in tropical environments such as Puerto Rico.
      Our objective was to examine whether glucan exposure is associated with degree of
      atopy or visits to the emergency department (ED)/urgent care for asthma in Puerto
      Rican children. METHODS: This was a cross-sectional study of 317 children aged 6
      to 14 years with (cases, n = 160) and without (control subjects, n = 157) asthma
      in San Juan, Puerto Rico. Our primary outcomes were the number of positive skin
      tests to allergens (range, 0-15) and (in cases only) having had at least one
      visit to the ED/urgent care for asthma in the prior year. Levels of glucan,
      endotoxin, peptidoglycan, and five allergens (Der p 1, Bla g 2, Fel d 1, Can f 1,
      and Mus m 1) were measured in samples of house dust. Linear or logistic
      regression was used for the multivariate analysis. MEASUREMENTS AND MAIN RESULTS:
      In a multivariate analysis adjusting for case-control status, mouse allergen, and
      other covariates, children exposed to glucan levels in the second and third
      quartiles had approximately two more positive skin tests than those in the lowest
      quartile (P < 0.01 in both instances). Among children with asthma, exposure to
      the highest quartile of glucan was associated with nearly ninefold greater odds
      of one or more visits to the ED/urgent care for asthma (95% confidence interval
      for adjusted odds ratio, 2.7-28.4; P < 0.001). CONCLUSIONS: Our results suggest
      that indoor fungal exposure leads to an increased degree of atopy and visits to
      the ED/urgent care for asthma in Puerto Rican children.

PMID- 24915165
TI  - Inhibition of STAT3 activity re-activates anti-tumor immunity but fails to
      restore the immunogenicity of tumor cells in a B-cell lymphoma model.
AB  - A large number of patients with advanced lymphoma become refractory or relapse
      after initial treatment due to the persistence of minimal residual disease. Ideal
      immunotherapy strategy for eradicating the minimal residual disease of lymphoma
      and preventing the tendency to relapse need to be developed. Here, we use a mice
      model mimicked the disease entities of aggressive B-cell lymphoma dynamically to
      analyze the host anti-lymphoma immunity during the progression of lymphoma. We
      have shown that STAT3 activity was gradually enhanced in host immune effector
      cells with the progression of lymphoma. Inhibition of the STAT3 activity with a
      small molecule inhibitor was able to effectively enhance the function of both
      host innate and adaptive immunity, and thereby delayed the progression of
      lymphoma. Despite the therapeutic benefits were achieved by using of the STAT3
      inhibitor, disrupting of STAT3 pathway did not prevent the eventual development
      of lymphoma due to the presence of point mutation of beta2M, which controls
      immune recognition by T cells. Our findings highlight the complexity of the
      mechanism of immune evasion; therefore a detailed analysis of genes involved in
      the immune recognition process should be essential before an elegant
      immunotherapy strategy could be conducted. 

PMID- 24915168
TI  - Synthesis, characterization and biological evaluation of
      carboranylmethylbenzo[b]acridones as novel agents for boron neutron capture
      therapy.
AB  - Herein we present the synthesis and characterization of benzo[b]acridin-12(7H)
      ones bearing carboranyl moieties and test their biological effectiveness as boron
      neutron capture therapy (BNCT) agents in cancer treatment. The cellular uptake of
      these novel compounds into the U87 human glioblastoma cells was evaluated by
      boron analysis (ICP-MS) and by fluorescence imaging (confocal microscopy). The
      compounds enter the U87 cells exhibiting a similar profile, i.e., preferential
      accumulation in the cytoskeleton and membranes and a low cytotoxic activity (IC50
      values higher than 200 MUM). The cytotoxic activity and cellular morphological
      alterations after neutron irradiation in the Portuguese Research Reactor (6.6 *
      10(7) neutrons cm(-2) s(-1), 1 MW) were evaluated by the MTT assay and by
      electron microscopy (TEM). Post-neutron irradiation revealed that BNCT has a
      higher cytotoxic effect on the cells. Accumulation of membranous whorls in the
      cytoplasm of cells treated with one of the compounds correlates well with the
      cytotoxic effect induced by radiation. Results provide a strong rationale for
      considering one of these compounds as a lead candidate for a new generation of
      BNCT agents. 

PMID- 24915169
TI  - Conjugated microporous polytriphenylamine networks.
AB  - Conjugated microporous polytriphenylamine networks with surface areas of 530 m(2)
      g(-1) were synthesized via Buchwald-Hartwig coupling, resulting in high CO2
      uptake (up to 6.5 wt%) and CO2-N2 selectivity (75) at 1 bar and 303 K. 

PMID- 24915170
TI  - Effects of alcoholic beverage control policies and contextual factors on alcohol
      consumption and its related harms in France from 1960 to 2000.
AB  - Important social changes such as urbanization, increases in female education and
      employment, and increased incomes have occurred in France from 1960 to 2000 along
      with a major decrease in alcoholic beverage consumption (from 25 L pure alcohol
      per inhabitant 15 years and old to 13 L); especially due to wine consumption
      decrease. These changes in drinking patterns are associated with significant
      decreases in alcohol consumption-related harms (liver disease mortality and
      transport accident mortality). Several alcoholic beverage consumption control
      policy measures were also created during this period. This study explores the
      impact of these policies measure on alcohol consumption and alcohol consumption
      related harms, adjusted with selected social changes. France's control policy has
      been associated, partially, with regressive effects on alcohol consumption but
      not on alcohol consumption-related harms. Study limitations are noted. 

PMID- 24915171
TI  - Cosmetic doping--when anabolic-androgenic steroids are not enough.
AB  - Doping is considered to be a major sports problem. This article describes a new
      threat and challenge to the sport of bodybuilding; the nonmedical use of a
      chemical in order to mimic muscle hypertrophy. Although muscle fillers are not
      new, being used for cosmetic purposes in medicine for a long time, the illegal
      use of muscle fillers has been increasing during the last few years and decades.
      The history of cosmetic doping, with particular attention to the Brazilian case,
      is discussed. Limitations are noted and future needed research is suggested. 

PMID- 24915172
TI  - Trends in consumption of alcoholic beverages and policy interventions in Europe:
      an uncertainty "associated" perspective.
AB  - Having qualitatively investigated, both the temporal curves of alcoholic beverage
      consumption trends and the introduction of preventive alcohol policy measures in
      six European countries during the 1960s-2000s, drinking control policy measures
      often appeared to operate as co-factors of change, while during some periods of
      time they were not even present even if effective consumption changes were
      occurring. Study limitations are noted. 

PMID- 24915173
TI  - Prospective clinical assessment using Sideline Concussion Assessment Tool-2
      testing in the evaluation of sport-related concussion in college athletes.
AB  - OBJECTIVE: To evaluate the utility of the Sideline Concussion Assessment Tool
      (SCAT)-2 in collegiate athletes with sport-related concussion. DESIGN:
      Prospective cross-sectional study with baseline testing and serial repeat testing
      after concussion in contact sport athletes and non-concussed control athletes.
      SETTING: Division I University. PARTICIPANTS: Male and female club rugby and
      varsity athletes. INTERVENTIONS: Baseline measures of concussion symptoms,
      cognitive function, and balance were obtained using the SCAT-2. Serial postinjury
      testing was conducted as clinically indicated. MAIN OUTCOME MEASURES: The SCAT-2
      total and subset scores were calculated and evaluated at baseline and after
      injury. RESULTS: The total SCAT-2 score and the composite scores of symptoms,
      symptom severity, and balance were significantly different in concussed groups
      after injury when compared with baseline. When comparing performance in concussed
      versus control athletes, all subcomponents of the SCAT-2 were significantly
      different. No differences in baseline SCAT-2 scores were seen based on self
      reported history of concussion. At baseline, anxiety and depression screening
      scores were associated with higher symptom scores. When compared with baseline, a
      3.5-point drop in SCAT-2 score had 96% sensitivity and 81% specificity in
      detecting concussion. When examined to exclude baseline scores, a cutoff value of
      74.5 was associated with 83% sensitivity and 91% specificity in predicting
      concussion versus control status. CONCLUSIONS: The SCAT-2 total composite score
      and each subcomponent are useful in the assessment of concussion. As SCAT-3 is
      similar to SCAT-2, it is expected that it too will be a useful tool.

PMID- 24915174
TI  - The club-level road cyclist: injury, pain, and performance.
AB  - OBJECTIVE: The aims of this study were to (1) examine riding habits of injured
      cyclists, (2) identify factors related to seeking medical treatment, (3)
      investigate performance of recreational road cyclists compared with established
      norms regarding strength and flexibility measures, and (4) propose cycling
      specific injury risk factors. DESIGN: Observational and prospective study.
      SETTING: Cycling store and bicycle distribution company. PARTICIPANTS: Sixty
      three experienced road cyclists. ASSESSMENT OF RISK FACTORS: Initial data
      collection included a questionnaire. A 2-week training diary and 8 weekly follow
      up injury questionnaires were also collected. MAIN OUTCOME MEASURES: Training
      habits and injury history, bike fit, flexibility, and isometric, dynamic, and
      plyometric strength measures. RESULTS: Participants were likely to have an injury
      at baseline, and chronic pain was common. Cyclists trained for an equal quantity
      of time irrespective of experiencing pain. Injury severity in terms of pain level
      and participant age were factors in seeking medical care. Our participants
      performed poorly on our testing protocol compared with available norms.
      Flexibility, strength, and bike fit measures did not predict injury. Previous
      injury predicted prospective injury. The knee and lumbar region were most
      frequently injured. CONCLUSIONS: Cycling is a sport in which injury risk and
      prevention need to be further studied. Cyclists are frequently injured but
      continue to participate in cycling at volumes equal to their healthy peers.
      CLINICAL RELEVANCE: This study outlines a clinically reproducible cyclist
      assessment and discusses behaviors common to the cycling patient.

PMID- 24915175
TI  - Preventive effects of 10-day supplementation with saffron and indomethacin on the
      delayed-onset muscle soreness.
AB  - OBJECTIVE: Delayed-onset muscle soreness (DOMS) often occurs after unaccustomed
      eccentric exercise and reduces exercise performance. We aimed to study the
      preventive effects of saffron and indomethacin on the biochemical and functional
      indicators of DOMS after 1-session eccentric exercise. DESIGN: A 10-day,
      randomized, double-blind, placebo-controlled, pretest-posttest design. SETTING:
      Controlled research laboratory. PARTICIPANTS: Thirty-nine nonactive male
      university students randomly divided into saffron (n = 12), indomethacin (n =
      12), and control (n = 15) groups. INTERVENTIONS: Saffron group received 1 capsule
      containing dried saffron powder (n = 12, 300 mg/d), indomethacin group received
      75 mg indomethacin (n = 12, 25 mg thrice a day), and control group (n = 15)
      received placebo capsules, 1 week before and 3 days after eccentric exercise. Ten
      days before and 24, 48, and 72 hours after muscle soreness protocol, the maximum
      isometric and isotonic forces, plasma creatine kinase (CK), plasma lactate
      dehydrogenase (LDH), perceived pain, knee range of movement, and thigh
      circumference were measured. Muscle soreness protocol was performed with a weight
      load equal to 80% of the maximum isotonic force in 4 sessions with 20 repetitions
      and 3-minute rest in between. MAIN OUTCOME MEASURES: This study shows that 10-day
      supplementation with 300 mg saffron significantly decreased the CK and LDH
      concentrations (P < 0.0001). In the saffron group, there was no decline in
      maximum isometric and isotonic forces after eccentric exercise, but a significant
      decline in the isometric force was observed in the control group (P < 0.0001). No
      pain was reported in the saffron group, whereas the indomethacin group
      experienced pain before 72 hours (P < 0.001). CONCLUSIONS: Results obtained from
      the current novel research indicate a strong preventive effect of 10-day
      supplementation with saffron on the DOMS. CLINICAL RELEVANCE: The saffron can be
      used to prevent DOMS and alleviate the DOMS symptoms.

PMID- 24915176
TI  - Unzipping carbon nanotubes at high impact.
AB  - The way nanostructures behave and mechanically respond to high impact collision
      is a topic of intrigue. For anisotropic nanostructures, such as carbon nanotubes,
      this response will be complicated based on the impact geometry. Here we report
      the result of hypervelocity impact of nanotubes against solid targets and show
      that impact produces a large number of defects in the nanotubes, as well as rapid
      atom evaporation, leading to their unzipping along the nanotube axis. Fully
      atomistic reactive molecular dynamics simulations are used to gain further
      insights of the pathways and deformation and fracture mechanisms of nanotubes
      under high energy mechanical impact. Carbon nanotubes have been unzipped into
      graphene nanoribbons before using chemical treatments but here the instability of
      nanotubes against defect formation, fracture, and unzipping is revealed purely
      through mechanical impact.

PMID- 24915177
TI  - A comparison of protein kinases inhibitor screening methods using both enzymatic
      activity and binding affinity determination.
AB  - Binding assays are increasingly used as a screening method for protein kinase
      inhibitors; however, as yet only a weak correlation with enzymatic activity-based
      assays has been demonstrated. We show that the correlation between the two types
      of assays can be improved using more precise screening conditions. Furthermore a
      marked improvement in the correlation was found by using kinase constructs
      containing the catalytic domain in presence of additional domains or subunits. 

PMID- 24915178
TI  - Rapid determination of the chemical oxygen demand of water using a thermal
      biosensor.
AB  - In this paper we describe a thermal biosensor with a flow injection analysis
      system for the determination of the chemical oxygen demand (COD) of water
      samples. Glucose solutions of different concentrations and actual water samples
      were tested, and their COD values were determined by measuring the heat generated
      when the samples passed through a column containing periodic acid. The biosensor
      exhibited a large linear range (5 to 3000 mg/L) and a low detection limit (1.84
      mg/L). It could tolerate the presence of chloride ions in concentrations of 0.015
      M without requiring a masking agent. The sensor was successfully used for
      detecting the COD values of actual samples. The COD values of water samples from
      various sources were correlated with those obtained by the standard dichromate
      method; the linear regression coefficient was found to be 0.996. The sensor is
      environmentally friendly, economical, and highly stable, and exhibits good
      reproducibility and accuracy. In addition, its response time is short, and there
      is no danger of hazardous emissions or external contamination. Finally, the
      samples to be tested do not have to be pretreated. These results suggest that the
      biosensor is suitable for the continuous monitoring of the COD values of actual
      wastewater samples. 

PMID- 24915179
TI  - An adaptive 6-DOF tracking method by hybrid sensing for ultrasonic endoscopes.
AB  - In this paper, a novel hybrid sensing method for tracking an ultrasonic endoscope
      within the gastrointestinal (GI) track is presented, and the prototype of the
      tracking system is also developed. We implement 6-DOF localization by sensing
      integration and information fusion. On the hardware level, a tri-axis gyroscope
      and accelerometer, and a magnetic angular rate and gravity (MARG) sensor array
      are attached at the end of endoscopes, and three symmetric cylindrical coils are
      placed around patients' abdomens. On the algorithm level, an adaptive fast
      quaternion convergence (AFQC) algorithm is introduced to determine the
      orientation by fusing inertial/magnetic measurements, in which the effects of
      magnetic disturbance and acceleration are estimated to gain an adaptive
      convergence output. A simplified electro-magnetic tracking (SEMT) algorithm for
      dimensional position is also implemented, which can easily integrate the AFQC's
      results and magnetic measurements. Subsequently, the average position error is
      under 0.3 cm by reasonable setting, and the average orientation error is 1
      degrees  without noise. If magnetic disturbance or acceleration exists, the
      average orientation error can be controlled to less than 3.5 degrees . 

PMID- 24915180
TI  - Electrocatalytic miRNA detection using cobalt porphyrin-modified reduced graphene
      oxide.
AB  - Metalated porphyrins have been described to bind nucleic acids. Additionally,
      cobalt porphyrins present catalytic properties towards oxygen reduction. In this
      work, a carboxylic acid-functionalized cobalt porphyrin was physisorbed on
      reduced graphene oxide, then immobilized on glassy carbon electrodes. The
      carboxylic groups were used to covalently graft amino-terminated oligonucleotide
      probes which are complementary to a short microRNA target. It was shown that the
      catalytic oxygen electroreduction on cobalt porphyrin increases upon
      hybridization of miRNA strand ("signal-on" response). Current changes are
      amplified compared to non-catalytic amperometric system. Apart from oxygen, no
      added reagent is necessary. A limit of detection in the sub-nanomolar range was
      reached. This approach has never been described in the literature. 

PMID- 24915181
TI  - Dealing with the effects of sensor displacement in wearable activity recognition.
AB  - Most wearable activity recognition systems assume a predefined sensor deployment
      that remains unchanged during runtime. However, this assumption does not reflect
      real-life conditions. During the normal use of such systems, users may place the
      sensors in a position different from the predefined sensor placement. Also,
      sensors may move from their original location to a different one, due to a loose
      attachment. Activity recognition systems trained on activity patterns
      characteristic of a given sensor deployment may likely fail due to sensor
      displacements. In this work, we innovatively explore the effects of sensor
      displacement induced by both the intentional misplacement of sensors and self
      placement by the user. The effects of sensor displacement are analyzed for
      standard activity recognition techniques, as well as for an alternate robust
      sensor fusion method proposed in a previous work. While classical recognition
      models show little tolerance to sensor displacement, the proposed method is
      proven to have notable capabilities to assimilate the changes introduced in the
      sensor position due to self-placement and provides considerable improvements for
      large misplacements. 

PMID- 24915182
TI  - Spatial and temporal patterns of apparent electrical conductivity: DUALEM vs.
      Veris sensors for monitoring soil properties.
AB  - The main objective of this study was to compare two apparent soil electrical
      conductivity (ECa) sensors (Veris 2000 XA and DUALEM 1S) for mapping variability
      of soil properties in a Mediterranean shallow soil. This study also aims at
      studying the effect of soil cover vegetation on the ECa measurement by the two
      types of sensors. The study was based on two surveys carried out under two very
      different situations: in February of 2012, with low soil moisture content (SMC)
      and with high and differentiated vegetation development (non grazed pasture), and
      in February of 2013, with high SMC and with short and relatively homogeneous
      vegetation development (grazed pasture). The greater temporal stability of Veris
      sensor, despite the wide variation in the SMC and vegetation ground cover
      indicates the suitability of using this sensor for monitoring soil properties in
      permanent pastures. The survey carried out with the DUALEM sensor in 2012 might
      have been affected by the presence of a 0.20 m vegetation layer at the soil
      surface, masking the soil properties. These differences should be considered in
      the selection of ECa sensing systems for a particular application. 

PMID- 24915184
TI  - J-tube technique for double-j stent insertion during laparoscopic upper urinary
      tract surgical procedures.
AB  - Double-J stent insertion has been generally performed during laparoscopic upper
      urinary tract (UUT) surgical procedures to prevent transient urinary tract
      obstruction and postoperative flank pain from ureteral edema and blood clots.
      Several restrictive conditions that make this procedure difficult and time
      consuming, however, include the coiled distal ends of the flexible Double-J stent
      and the limited bending angle of the laparoscopic instruments. To overcome these
      limitations, we devised a Double-J stent insertion method using the new J-tube
      technique. Between July 2011 and May 2013, Double-J stents were inserted using
      the J-tube technique in 33 patients who underwent a laparoscopic UUT surgical
      procedure by a single surgeon. The mean stent placement time was 4.8+/-2.7
      minutes, and there were no intraoperative complications. In conclusion, the J
      tube technique is a safe and time-saving method for Double-J stent insertion
      during laparoscopic surgical procedures.

PMID- 24915185
TI  - Size-dependent self-limiting oxidation of free palladium clusters.
AB  - Temperature-dependent gas phase ion trap experiments performed under
      multicollision conditions reveal a strongly size-dependent reactivity of Pd(x)(+)
      (x = 2-7) in the reaction with molecular oxygen. Yet, a particular stability and
      resistance to further oxidation is generally observed for reaction products with
      two oxygen molecules, Pd(x)O4(+). Complementary first-principles density
      functional theory simulations elucidate the details of the size-dependent bonding
      of oxygen to the small palladium clusters and are able to assign the pronounced
      occurrence of Pd(x)O4(+) complexes to a dissociatively chemisorbed bridging
      oxygen atomic structure which impedes the chemisorption of further oxygen
      molecules. The molecular physisorption of additional O2 is only observed at
      cryogenic temperatures. Additional experiments and simulations employing
      preoxidized clusters Pd(x)O(+) (x = 2-8) and Pd(x)O2(+) (x = 4-7) confirm the
      formation of the two different oxygen species.

PMID- 24915183
TI  - Flexible carbon nanotube films for high performance strain sensors.
AB  - Compared with traditional conductive fillers, carbon nanotubes (CNTs) have unique
      advantages, i.e., excellent mechanical properties, high electrical conductivity
      and thermal stability. Nanocomposites as piezoresistive films provide an
      interesting approach for the realization of large area strain sensors with high
      sensitivity and low manufacturing costs. A polymer-based nanocomposite with
      carbon nanomaterials as conductive filler can be deposited on a flexible
      substrate of choice and this leads to mechanically flexible layers. Such sensors
      allow the strain measurement for both integral measurement on a certain surface
      and local measurement at a certain position depending on the sensor geometry.
      Strain sensors based on carbon nanostructures can overcome several limitations of
      conventional strain sensors, e.g., sensitivity, adjustable measurement range and
      integral measurement on big surfaces. The novel technology allows realizing
      strain sensors which can be easily integrated even as buried layers in material
      systems. In this review paper, we discuss the dependence of strain sensitivity on
      different experimental parameters such as composition of the carbon
      nanomaterial/polymer layer, type of polymer, fabrication process and processing
      parameters. The insights about the relationship between film parameters and
      electromechanical properties can be used to improve the design and fabrication of
      CNT strain sensors. 

PMID- 24915186
TI  - Association between cutaneous nevi and breast cancer in the Nurses' Health Study:
      a prospective cohort study.
AB  - BACKGROUND: Cutaneous nevi are suggested to be hormone-related. We hypothesized
      that the number of cutaneous nevi might be a phenotypic marker of plasma hormone
      levels and predict subsequent breast cancer risk. METHODS AND FINDINGS: We
      followed 74,523 female nurses for 24 y (1986-2010) in the Nurses' Health Study
      and estimate the relative risk of breast cancer according to the number of
      cutaneous nevi. We adjusted for the known breast cancer risk factors in the
      models. During follow-up, a total of 5,483 invasive breast cancer cases were
      diagnosed. Compared to women with no nevi, women with more cutaneous nevi had
      higher risks of breast cancer (multivariable-adjusted hazard ratio, 1.04, 95%
      confidence interval [CI], 0.98-1.10 for 1-5 nevi; 1.15, 95% CI, 1.00-1.31 for 6
      14 nevi, and 1.35, 95% CI, 1.04-1.74 for 15 or more nevi; p for continuous trend
      = 0.003). Over 24 y of follow-up, the absolute risk of developing breast cancer
      increased from 8.48% for women without cutaneous nevi to 8.82% (95% CI, 8.31%
      9.33%) for women with 1-5 nevi, 9.75% (95% CI, 8.48%-11.11%) for women with 6-14
      nevi, and 11.4% (95% CI, 8.82%-14.76%) for women with 15 or more nevi. The number
      of cutaneous nevi was associated with increased risk of breast cancer only among
      estrogen receptor (ER)-positive tumors (multivariable-adjusted hazard ratio per
      five nevi, 1.09, 95% CI, 1.02-1.16 for ER+/progesterone receptor [PR]-positive
      tumors; 1.08, 95% CI, 0.94-1.24 for ER+/PR- tumors; and 0.99, 95% CI, 0.86-1.15
      for ER-/PR- tumors). Additionally, we tested plasma hormone levels according to
      the number of cutaneous nevi among a subgroup of postmenopausal women without
      postmenopausal hormone use (n = 611). Postmenopausal women with six or more nevi
      had a 45.5% higher level of free estradiol and a 47.4% higher level of free
      testosterone compared to those with no nevi (p for trend = 0.001 for both). Among
      a subgroup of 362 breast cancer cases and 611 matched controls with plasma
      hormone measurements, the multivariable-adjusted odds ratio for every five nevi
      attenuated from 1.25 (95% CI, 0.89-1.74) to 1.16 (95% CI, 0.83-1.64) after
      adjusting for plasma hormone levels. Key limitations in this study are that
      cutaneous nevi were self-counted in our cohort and that the study was conducted
      in white individuals, and thus the findings do not necessarily apply to other
      populations. CONCLUSIONS: Our results suggest that the number of cutaneous nevi
      may reflect plasma hormone levels and predict breast cancer risk independently of
      previously known factors.

PMID- 24915187
TI  - Assessment of the cost-effectiveness and clinical outcomes of a fourth-generation
      synchronous telehealth program for the management of chronic cardiovascular
      disease.
AB  - BACKGROUND: Telehealth programs are a growing field in the care of patients. The
      evolution of information technology has resulted in telehealth becoming a fourth
      generation synchronous program. However, long-term outcomes and cost
      effectiveness analysis of fourth-generation telehealth programs have not been
      reported in patients with chronic cardiovascular diseases. OBJECTIVE: We
      conducted this study to assess the clinical outcomes and cost-effectiveness of a
      fourth-generation synchronous telehealth program for patients with chronic
      cardiovascular diseases. METHODS: We retrospectively analyzed 575 patients who
      had joined a telehealth program and compared them with 1178 patients matched for
      sex, age, and Charlson comorbidity index. The program included: (1) instant
      transmission of biometric data, (2) daily telephone interview, and (3) continuous
      decision-making support. Data on hospitalization, emergency department (ED)
      visits, and medical costs were collected from the hospital's database and were
      adjusted to the follow-up months. RESULTS: The mean age was 64.5 years (SD 16.0).
      The mean number of monthly ED visits (mean 0.06 SD 0.13 vs mean 0.09 SD 0.23,
      P<.001), hospitalizations (mean 0.05 SD 0.12 vs mean 0.11 SD 0.21, P<.001),
      length of hospitalization (mean 0.77 days SD 2.78 vs mean 1.4 SD 3.6, P<.001),
      and intensive care unit admissions (mean 0.01 SD 0.07 vs mean 0.036 SD 0.14,
      P<.001) were lower in the telehealth group. The monthly mean costs of ED visits
      (mean US$20.90 SD 66.60 vs mean US$37.30 SD 126.20, P<.001), hospitalizations
      (mean US$386.30 SD 1424.30 vs mean US$878.20 SD 2697.20, P<.001), and all medical
      costs (mean US$587.60 SD 1497.80 vs mean US$1163.60 SD 3036.60, P<.001) were
      lower in the telehealth group. The intervention costs per patient were US$224.80
      per month. Multivariate analyses revealed that age, telehealth care, and Charlson
      index were the independent factors for ED visits, hospitalizations, and length of
      hospitalization. A bootstrap method revealed the dominant cost-effectiveness of
      telehealth care over usual care. CONCLUSIONS: Better cost-effectiveness and
      clinical outcomes were noted with the use of a fourth-generation synchronous
      telehealth program in patients with chronic cardiovascular diseases. The
      intervention costs of this new generation of telehealth program do not increase
      the total costs for patient care.

PMID- 24915188
TI  - Identification of NAD(P)H quinone oxidoreductase activity in azoreductases from
      P. aeruginosa: azoreductases and NAD(P)H quinone oxidoreductases belong to the
      same FMN-dependent superfamily of enzymes.
AB  - Water soluble quinones are a group of cytotoxic anti-bacterial compounds that are
      secreted by many species of plants, invertebrates, fungi and bacteria. Studies in
      a number of species have shown the importance of quinones in response to
      pathogenic bacteria of the genus Pseudomonas. Two electron reduction is an
      important mechanism of quinone detoxification as it generates the less toxic
      quinol. In most organisms this reaction is carried out by a group of flavoenzymes
      known as NAD(P)H quinone oxidoreductases. Azoreductases have previously been
      separate from this group, however using azoreductases from Pseudomonas aeruginosa
      we show that they can rapidly reduce quinones. Azoreductases from the same
      organism are also shown to have distinct substrate specificity profiles allowing
      them to reduce a wide range of quinones. The azoreductase family is also shown to
      be more extensive than originally thought, due to the large sequence divergence
      amongst its members. As both NAD(P)H quinone oxidoreductases and azoreductases
      have related reaction mechanisms it is proposed that they form an enzyme
      superfamily. The ubiquitous and diverse nature of azoreductases alongside their
      broad substrate specificity, indicates they play a wide role in cellular survival
      under adverse conditions. 

PMID- 24915189
TI  - Effects of novel isoform-selective phosphoinositide 3-kinase inhibitors on
      natural killer cell function.
AB  - Phosphoinositide 3-kinases (PI3Ks) are promising targets for therapeutic
      development in cancer. The class I PI3K isoform p110alpha has received
      considerable attention in oncology because the gene encoding p110alpha (PIK3CA)
      is frequently mutated in human cancer. However, little is known about the
      function of p110alpha in lymphocyte populations that modulate tumorigenesis. We
      used recently developed investigational inhibitors to compare the function of
      p110alpha and other isoforms in natural killer (NK) cells, a key cell type for
      immunosurveillance and tumor immunotherapy. Inhibitors of all class I isoforms
      (pan-PI3K) significantly impaired NK cell-mediated cytotoxicity and antibody
      dependent cellular cytotoxicity against tumor cells, whereas p110alpha-selective
      inhibitors had no effect. In NK cells stimulated through NKG2D, p110alpha
      inhibition modestly reduced PI3K signaling output as measured by AKT
      phosphorylation. Production of IFN-gamma and NK cell-derived chemokines was
      blocked by a pan-PI3K inhibitor and partially reduced by a p110deltainhibitor,
      with lesser effects of p110alpha inhibitors. Oral administration of mice with
      MLN1117, a p110alpha inhibitor in oncology clinical trials, had negligible
      effects on NK subset maturation or terminal subset commitment. Collectively,
      these results support the targeting of PIK3CA mutant tumors with selective
      p110alpha inhibitors to preserve NK cell function. 

PMID- 24915191
TI  - Speckle-tracking echocardiography elucidates the effect of pacing site on left
      ventricular synchronization in the normal and infarcted rat myocardium.
AB  - BACKGROUND: Right ventricular (RV) pacing generates regional disparities in
      electrical activation and mechanical function (ventricular dyssynchrony). In
      contrast, left ventricular (LV) or biventricular (BIV) pacing can improve cardiac
      efficiency in the setting of ventricular dyssynchrony, constituting the rationale
      for cardiac resynchronization therapy (CRT). Animal models of ventricular
      dyssynchrony and CRT currently relay on large mammals which are expensive and not
      readily available to most researchers. We developed a methodology for double-site
      epicardial pacing in conscious rats. Here, following post-operative recovery, we
      compared the effects of various pacing modes on LV dyssynchrony in normal rats
      and in rats with ischemic cardiomyopathy. METHODS: Two bipolar electrodes were
      implanted in rats as follows: Group A (n = 6) right atrial (RA) and RV sites;
      Group B (n = 7) RV and LV sites; Group C (n = 8) as in group B in combination
      with left coronary artery ligation. Electrodes were exteriorized through the
      back. Following post-operative recovery, two-dimensional transthoracic
      echocardiography was performed during pacing through the different electrodes.
      Segmental systolic circumferential strain (Ecc) was used to evaluate LV
      dyssynchrony. RESULTS: In normal rats, RV pacing induced marked LV dyssynchrony
      compared to RA pacing or sinus rhythm, as measured by the standard deviation (SD)
      of segmental time to peak Ecc, SD of peak Ecc, and the average delay between
      opposing ventricular segments. LV pacing and, to a greater extend BIV pacing
      diminished the LV dyssynchrony compared to RV pacing. In rats with extensive MI,
      the effects of LV and BIV pacing were markedly attenuated, and the response of
      individual animals was variable. CONCLUSIONS: Rodent cardiac pacing mimics
      important features seen in humans. This model may be developed as a simple new
      tool to study the pathophysiology of ventricular dyssynchrony and CRT.

PMID- 24915192
TI  - Gene-splitting technology: a novel approach for the containment of transgene flow
      in Nicotiana tabacum.
AB  - The potential impact of transgene escape on the environment and food safety is a
      major concern to the scientists and public. This work aimed to assess the effect
      of intein-mediated gene splitting on containment of transgene flow. Two fusion
      genes, EPSPSn-In and Ic-EPSPSc, were constructed and integrated into N. tabacum,
      using Agrobacterium tumefaciens-mediated transformation. EPSPSn-In encodes the
      first 295 aa of the herbicide resistance gene 5-enolpyruvyl shikimate-3-phosphate
      synthase (EPSPS) fused with the first 123 aa of the Ssp DnaE intein (In), whereas
      Ic-EPSPSc encodes the 36 C-terminal aa of the Ssp DnaE intein (Ic) fused to the
      rest of EPSPS C terminus peptide sequences. Both EPSPSn-In and Ic-EPSPSc
      constructs were introduced into the same N. tabacum genome by genetic crossing.
      Hybrids displayed resistance to the herbicide N-(phosphonomethyl)-glycine
      (glyphosate). Western blot analysis of protein extracts from hybrid plants
      identified full-length EPSPS. Furthermore, all hybrid seeds germinated and grew
      normally on glyphosate selective medium. The 6-8 leaf hybrid plants showed
      tolerance of 2000 ppm glyphosate in field spraying. These results indicated that
      functional EPSPS protein was reassembled in vivo by intein-mediated trans
      splicing in 100% of plants. In order to evaluate the effect of the gene splitting
      technique for containment of transgene flow, backcrossing experiments were
      carried out between hybrids, in which the foreign genes EPSPSn-In and Ic-EPSPSc
      were inserted into different chromosomes, and non-transgenic plants NC89. Among
      the 2812 backcrossing progeny, about 25% (664 plantlets) displayed glyphosate
      resistance. These data indicated that transgene flow could be reduced by 75%.
      Overall, our findings provide a new and highly effective approach for biological
      containment of transgene flow. 

PMID- 24915193
TI  - Anticancer properties of peptide fragments of hair proteins.
AB  - The primary function of hair and fur covering mammalian skin is to provide
      mechanical and thermal protection for the body. The proteins that constitute hair
      are extremely resistant to degradation by environmental factors. However, even
      durable materials can be slowly broken down by mechanical stresses,
      biodegradation mediated by endogenous enzymes in the skin or host microbes. We
      hypothesised that the biodegradation products of hair may possess bioprotective
      properties, which supplement their physical protective properties. Although
      evolutionary processes have led to a reduction in the amount of hair on the human
      body, it is possible that the bioprotective properties of hair biodegradation
      products have persisted. The human skin is exposed to various environmental
      carcinogenic factors. Therefore, we hypothesised that the potential bioprotective
      mechanisms of hair degradation products affect melanoma growth. We used pepsin to
      partially digest hair enzymatically, and this process produced a water-soluble
      lysate containing a mixture of peptides, including fragments of keratin and
      keratin-associated proteins. We found out that the mixtures of soluble peptides
      obtained from human hair inhibited the proliferation of human melanoma cells in
      vitro. Moreover, the hair-derived peptide mixtures also inhibited the
      proliferation of B lymphoma cells and urinary bladder cancer cells. Normal human
      cells varied in their susceptibility to the effects of the lysate; the hair
      derived peptide mixtures modulated the proliferation of normal human fibroblasts
      but did not inhibit the proliferation of human mesenchymal cells derived from
      umbilical cord stromal cells. These results suggest that hair-derived peptides
      may represent a new class of anti-proliferative factors derived from basically
      structural proteins. Identification of active regulatory compounds and
      recognition of the mechanism of their action might pave the way to elaboration of
      new anticancer drugs. 

PMID- 24915195
TI  - Effect of rehabilitation program on endocrinological parameters in patients with
      COPD and in healthy subjects.
AB  - BACKGROUND: Skeletal muscle wasting commonly occurs in patients with chronic
      obstructive pulmonary disease (COPD) and has been associated with the presence of
      systemic inflammation and endocrinological disturbance. The aim of this study is
      to analyze the effect of rehabilitation program on the balance of anabolic versus
      catabolic hormone in patients with COPD and in healthy subjects. METHODS:
      Nineteen patients with COPD and 16 age-matched healthy subjects undertooked
      exercise training 3 days/week for 8 weeks. Before and after the training program
      the concentration of growth hormone (GH), Insulin-Like Growth Factor-1 (IGF-1),
      Insulin-like Growth Factor-Binding Protein 3 (IGF-BP3), testosterone and cortisol
      in serum were determined. The exercise measurements included a 6-Minute Walking
      Test (6MWT). RESULTS: After 8 weeks, there was no significant change in lung
      function in patients with COPD and healthy subjects. Growth hormone, Insulin-like
      Growth Factor-1 and Insulin-like Growth Factor-Binding Protein 3 increased
      significantly after rehabilitation training (p < 0.01). The rehabilitation
      program improves the testosterone/cortisol ratio (T/C ratio) in both groups.
      There is a significant improvement in the 6-Minute Walking distance (6MWD) in
      both groups (p < 0.01). Dyspnea and heart rate at rest and at the peak of the 6
      Minute Walking Test (6MWT) decreased significantly after training program (p <
      0.01). CONCLUSION: Pulmonary rehabilitation induces an improvement of the
      anabolic process and reduces proteine distruction by the modifications in
      endocrinological factors regulating skeletal muscle in patients with COPD.

PMID- 24915194
TI  - Calibrating snakehead diversity with DNA barcodes: expanding taxonomic coverage
      to enable identification of potential and established invasive species.
AB  - Detecting and documenting the occurrence of invasive species outside their native
      range requires tools to support their identification. This can be challenging for
      taxa with diverse life stages and/or problematic or unresolved morphological
      taxonomies. DNA barcoding provides a potent method for identifying invasive
      species, as it allows for species identification at all life stages, including
      fragmentary remains. It also provides an efficient interim taxonomic framework
      for quantifying cryptic genetic diversity by parsing barcode sequences into
      discontinuous haplogroup clusters (typical of reproductively isolated species)
      and labelling them with unique alphanumeric identifiers. Snakehead fishes are a
      diverse group of opportunistic predators endemic to Asia and Africa that may
      potentially pose significant threats as aquatic invasive species. At least three
      snakehead species (Channa argus, C. maculata, and C. marulius) are thought to
      have entered North America through the aquarium and live-food fish markets, and
      have established populations, yet their origins remain unclear. The objectives of
      this study were to assemble a library of DNA barcode sequences derived from
      expert identified reference specimens in order to determine the identity and aid
      invasion pathway analysis of the non-indigenous species found in North America
      using DNA barcodes. Sequences were obtained from 121 tissue samples representing
      25 species and combined with public records from GenBank for a total of 36
      putative species, which then partitioned into 49 discrete haplogroups. Multiple
      divergent clusters were observed within C. gachua, C. marulius, C. punctata and
      C. striata suggesting the potential presence of cryptic species diversity within
      these lineages. Our findings demonstrate that DNA barcoding is a valuable tool
      for species identification in challenging and under-studied taxonomic groups such
      as snakeheads, and provides a useful framework for inferring invasion pathway
      analysis. 

PMID- 24915196
TI  - An ongoing role for structural sarcomeric components in maintaining Drosophila
      melanogaster muscle function and structure.
AB  - Animal muscles must maintain their function while bearing substantial mechanical
      loads. How muscles withstand persistent mechanical strain is presently not well
      understood. The basic unit of muscle is the sarcomere, which is primarily
      composed of cytoskeletal proteins. We hypothesized that cytoskeletal protein
      turnover is required to maintain muscle function. Using the flight muscles of
      Drosophila melanogaster, we confirmed that the sarcomeric cytoskeleton undergoes
      turnover throughout adult life. To uncover which cytoskeletal components are
      required to maintain adult muscle function, we performed an RNAi-mediated
      knockdown screen targeting the entire fly cytoskeleton and associated proteins.
      Gene knockdown was restricted to adult flies and muscle function was analyzed
      with behavioural assays. Here we analyze the results of that screen and
      characterize the specific muscle maintenance role for several hits. The screen
      identified 46 genes required for muscle maintenance: 40 of which had no
      previously known role in this process. Bioinformatic analysis highlighted the
      structural sarcomeric proteins as a candidate group for further analysis.
      Detailed confocal and electron microscopic analysis showed that while muscle
      architecture was maintained after candidate gene knockdown, sarcomere length was
      disrupted. Specifically, we found that ongoing synthesis and turnover of the key
      sarcomere structural components Projectin, Myosin and Actin are required to
      maintain correct sarcomere length and thin filament length. Our results provide
      in vivo evidence of adult muscle protein turnover and uncover specific functional
      defects associated with reduced expression of a subset of cytoskeletal proteins
      in the adult animal. 

PMID- 24915198
TI  - Boronyl chemistry: the BO group as a new ligand in gas-phase clusters and
      synthetic compounds.
AB  - Boronyl (BO) is a monovalent sigma radical with a robust B=O triple bond.
      Although BO/BO(-) are isovalent to CN/CN(-) and CO, the chemistry of boronyl has
      remained relatively unknown until recently, whereas CN/CN(-) and CO are well
      known inorganic ligands. Further analogy may be established for BO versus H or Au
      ligands, which are all monovalent sigma radicals. This Account intends to provide
      an overview of research activities over the past few years that are relevant to
      the development of boronyl chemistry, in particular, in size-selected gaseous
      clusters containing BO. The systems covered herein include transition metal
      boronyl clusters, carbon boronyl clusters, boron oxide clusters and boron boronyl
      complexes, the boronyl boroxine, and the first synthetic Pt-BO bulk compound. In
      these boronyl clusters and compounds, the BO groups show remarkable structural
      and chemical integrity as a ligand. Among transition metal boronyls, gold
      monoboronyl clusters Aun(BO)(-) and Aun(BO) (n = 1-3) have been characterized,
      and they are shown to possess electronic and structural properties similar to the
      corresponding Au(n+1)(-) and Au(n+1) bare clusters, demonstrating the BO/Au
      analogy. The Au-B bonding in the Au-BO clusters is highly covalent. A recent
      advance in boronyl chemistry is the successful synthesis and isolation of the
      first boronyl compound, trans-[(Cy3P)2BrPt(BO)]. This unique Pt-BO compound and
      other potential transition metal boronyl compounds may find applications in
      catalysis and as chemical building blocks. Carbon boronyl clusters versus boron
      carbonyl clusters is a topic of interest in designing new aromatic complexes.
      Experimental and theoretical data obtained to date show that carbon boronyl
      clusters are generally far more stable than their boron carbonyl counterparts,
      highlighting the potency of boronyl as a ligand in aromatic compounds. Notably,
      in light of the BO/H analogy, the perfectly hexagonal (CBO)6 cluster is a carbon
      boronyl analogue of benzene. The BO groups also dominate the structures and
      bonding of boron oxide clusters and boron boronyl complexes, in which BO groups
      occupy terminal, bridging, or face-capping positions. The bridging eta(2)-BO
      groups feature three-center two-electron bonds, akin to the BHB tau bonds in
      boranes. A close isolobal analogy is thus established between boron oxide
      clusters and boranes, offering vast opportunities for the rational design of
      novel boron oxide clusters and compounds. Boron boronyl clusters may also serve
      as molecular models for mechanistic understanding of the combustion of boron and
      boranes. An effort to tune the B versus O composition in boron oxide clusters
      leads to the discovery of boronyl boroxine, D3h B3O3(BO)3, an analogue of
      boroxine and borazine and a new member of the "inorganic benzene" family.
      Furthermore, a unique concept of pi and sigma double conjugation is proposed for
      the first time to elucidate the structures and bonding in the double-chain
      nanoribbon boron diboronyl clusters, which appear to be inorganic analogues of
      polyenes, cumulenes, and polyynes. This Account concludes with a brief outlook
      for the future directions in this emerging and expanding research field.

PMID- 24915197
TI  - Downregulation of immediate-early genes linking to suppression of neuronal
      plasticity in rats after 28-day exposure to glycidol.
AB  - We previously found that the 28-day oral toxicity study of glycidol at
      200mg/kg/day in rats resulted in axonopathy in both the central and peripheral
      nervous systems and aberrations in the late-stage of hippocampal neurogenesis
      targeting the process of neurite extension. To capture the neuronal parameters in
      response to glycidol toxicity, these animals were subjected to region-specific
      global gene expression profiling in four regions of cerebral and cerebellar
      architectures, followed by immunohistochemical analysis of selected gene
      products. Expression changes of genes related to axonogenesis and synaptic
      transmission were observed in the hippocampal dentate gyrus, cingulate cortex and
      cerebellar vermis at 200mg/kg showing downregulation in most genes. In the corpus
      callosum, genes related to growth, survival and functions of glial cells
      fluctuated their expression. Immunohistochemically, neurons expressing gene
      products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their
      number in the dentate granule cell layer, cingulate cortex and cerebellar vermis.
      We also applied immunohistochemical analysis in rat offspring after developmental
      exposure to glycidol through maternal drinking water. The results revealed
      increases of Arc(+) neurons at 1000ppm and Fos(+) neurons at >=300ppm in the
      dentate granule cell layer of offspring only at the adult stage. These results
      suggest that glycidol suppressed neuronal plasticity in the brain after 28-day
      exposure to young adult animals, in contrast to the operation of restoration
      mechanism to increase neuronal plasticity at the adult stage in response to
      aberrations in neurogenesis after developmental exposure. 

PMID- 24915199
TI  - Competition for neuronal processing time: a physiological seizure control
      mechanism?
AB  - Cognitive means for seizure control remain underinvestigated in clinical
      epileptology. Since administration of a complex reaction time (CRT) test
      triggered by a seizure detection algorithm is a unique research paradigm, its
      effects on seizure frequency and severity were examined in 14 subjects undergoing
      invasive epilepsy surgery evaluation. These variables were compared with those of
      37 subjects evaluated using the same surgical protocol, but to whom the CRT test
      was not administered. The results were analyzed for statistical significance
      using the t-test and the chi-squared test. Eight of fourteen subjects who took
      the CRT test had fewer than 5 clinical seizures, and 7 of 14 subjects had fewer
      than 5 clinical and subclinical seizures over 8.9 days compared with 37 subjects
      who did not take this test, each of whom had a minimum of 5 clinical seizures
      over 6.7 days (chi-square=25.08; p<0.001). The monitoring duration difference
      (2.2 days longer for CRT test takers) was statistically significant (p~0.04). In
      one subject, seizure severity was lower (p<0.001) during testing compared with
      nontesting periods. It is posited that seizure frequency reduction is a
      beneficial, unconditioned, and, probably, contingent effect of the CRT test.
      These and other experimental observations form the basis for a hypothetical
      physiological antiseizure mechanism, the "competition for neuronal processing
      time".

PMID- 24915200
TI  - An investigation of state population characteristics that moderate the
      relationship of state seat belt law and use in the United States.
AB  - OBJECTIVES: Primary enforcement laws have been shown to be effective methods for
      increasing seat belt use at the state level. METHOD: This study investigates
      state differences in the effectiveness of primary enforcement laws by assessing
      whether a state's academic achievement, health ranking, economic prosperity,
      violent crime rates, government effectiveness, gender distribution, or proportion
      of rural roads moderate the relationship between those laws and seat belt
      compliance rates. RESULTS: Aggregate state-level academic achievement, health
      ranking, government effectiveness, and proportion of rural roads uniquely
      moderated the seat belt use differences between primary and secondary enforcement
      states. CONCLUSIONS: This evidence suggests that cultural, social, and
      demographic differences among regions may be important factors in explaining
      state-level differences in the effectiveness of primary enforcement of seat belt
      laws.

PMID- 24915201
TI  - Lab to farm: applying research on plant genetics and genomics to crop
      improvement.
AB  - Over the last 300 years, plant science research has provided important knowledge
      and technologies for advancing the sustainability of agriculture. In this Essay,
      I describe how basic research advances have been translated into crop
      improvement, explore some lessons learned, and discuss the potential for current
      and future contribution of plant genetic improvement technologies to continue to
      enhance food security and agricultural sustainability.

PMID- 24915202
TI  - Intakes of dairy products and calcium and obesity in Korean adults: Korean
      National Health and Nutrition Examination Surveys (KNHANES) 2007-2009.
AB  - BACKGROUND: The possible effects of dairy product intake against obesity have
      been suggested in animal studies; however, the association is still not well
      established in epidemiological studies. Few studies in Asian countries with
      relatively low intake of dairy products exist. OBJECTIVE: We investigated the
      association between dairy products and calcium intake and obesity in Korean
      population with relatively low intake of dairy products. SUBJECTS AND METHODS:
      Our study population consisted of adults (n = 7173) aged 19-64 among participants
      of the 2007, 2008 and 2009 Korean National Health and Nutrition Examination
      Survey who had not made any attempt of intentional weight loss. Dietary intake
      data from food frequency questionnaire (FFQ) and 24-hour recall were used. Dairy
      products included milk and yogurt in the FFQ. Obesity was defined as BMI>=25
      kg/m2. RESULTS: Higher frequency of dairy product intake was associated with a
      reduced prevalence of obesity (OR = 0.63; 95% CI = 0.45-0.89 for >=2 times/day
      vs. <=1 time/month; p for trend = 0.003) using the intake data from FFQ.
      Similarly, high frequency of milk or yogurt intake had an inverse association
      with obesity. The association between milk and yogurt intake and obesity was
      similar when the intake from 24-hour recall was examined. Higher calcium intake
      from dairy products as well as total dietary calcium intake was associated with a
      decreased prevalence of obesity (OR = 0.83; 95% CI = 0.71-0.98 for highest vs.
      lowest quintile of dairy calcium intake; p for trend = 0.02, OR = 0.78; 95% CI =
      0.64-0.94 for highest vs. lowest quintile of total calcium intake; p for trend =
      0.04). The associations appeared to be stronger in women than in men. CONCLUSION:
      These results suggest that high consumption of dairy products is associated with
      a lower prevalence of obesity and that calcium in dairy products may be one of
      the components contributing to the association. Further longitudinal studies are
      warranted to replicate our findings.

PMID- 24915203
TI  - Automatic high-bandwidth calibration and reconstruction of arbitrarily sampled
      parallel MRI.
AB  - Today, many MRI reconstruction techniques exist for undersampled MRI data.
      Regularization-based techniques inspired by compressed sensing allow for the
      reconstruction of undersampled data that would lead to an ill-posed
      reconstruction problem. Parallel imaging enables the reconstruction of MRI images
      from undersampled multi-coil data that leads to a well-posed reconstruction
      problem. Autocalibrating pMRI techniques encompass pMRI techniques where no
      explicit knowledge of the coil sensivities is required. A first purpose of this
      paper is to derive a novel autocalibration approach for pMRI that allows for the
      estimation and use of smooth, but high-bandwidth coil profiles instead of a
      compactly supported kernel. These high-bandwidth models adhere more accurately to
      the physics of an antenna system. The second purpose of this paper is to
      demonstrate the feasibility of a parameter-free reconstruction algorithm that
      combines autocalibrating pMRI and compressed sensing. Therefore, we present
      several techniques for automatic parameter estimation in MRI reconstruction.
      Experiments show that a higher reconstruction accuracy can be had using high
      bandwidth coil models and that the automatic parameter choices yield an
      acceptable result. 

PMID- 24915204
TI  - Strategies to prevent central line-associated bloodstream infections in acute
      care hospitals: 2014 update.

PMID- 24915205
TI  - Strategies to prevent methicillin-resistant Staphylococcus aureus transmission
      and infection in acute care hospitals: 2014 update.

PMID- 24915206
TI  - Approaches for preventing healthcare-associated infections: go long or go wide?

PMID- 24915207
TI  - A national intervention to prevent the spread of carbapenem-resistant
      Enterobacteriaceae in Israeli post-acute care hospitals.
AB  - OBJECTIVE: Patients hospitalized in post-acute care hospitals (PACHs) constitute
      an important reservoir of antimicrobial-resistant bacteria. High carriage
      prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been observed
      among patients hospitalized in PACHs. The objective of the study is to describe
      the impact of a national infection control intervention on the prevalence of CRE
      in PACHs. DESIGN: A prospective cohort interventional study. SETTING: Thirteen
      PACHs in Israel. INTERVENTION: A multifaceted intervention was initiated between
      2008 and 2011 as part of a national program involving all Israeli healthcare
      facilities. The intervention has included (1) periodic on-site assessments of
      infection control policies and resources, using a score comprised of 16 elements;
      (2) assessment of risk factors for CRE colonization; (3) development of national
      guidelines for CRE control in PACHs involving active surveillance and contact
      isolation of carriers; and (4) 3 cross-sectional surveys of rectal carriage of
      CRE that were conducted in representative wards. RESULTS: The infection control
      score increased from 6.8 to 14.0 (P < .001) over the course of the study period.
      A total of 3,516 patients were screened in the 3 surveys. Prevalence of carriage
      among those not known to be carriers decreased from 12.1% to 7.9% (P = .008).
      Overall carrier prevalence decreased from 16.8% to 12.5% (P = .013). Availability
      of alcohol-based hand rub, appropriate use of gloves, and a policy of CRE
      surveillance at admission to the hospital were independently associated with
      lower new carrier prevalence. CONCLUSION: A nationwide infection control
      intervention was associated with enhanced infection control measures and a
      reduction in the prevalence of CRE in PACHs.

PMID- 24915208
TI  - Control of simultaneous outbreaks of carbapenemase-producing enterobacteriaceae
      and extensively drug-resistant Acinetobacter baumannii infection in an intensive
      care unit using interventions promoted in the Centers for Disease Control and
      Prevention 2012 carbapenemase-resistant Enterobacteriaceae Toolkit.
AB  - OBJECTIVE: We describe the efficacy of enhanced infection control measures,
      including those recommended in the Centers for Disease Control and Prevention's
      2012 carbapenem-resistant Enterobacteriaceae (CRE) toolkit, to control concurrent
      outbreaks of carbapenemase-producing Enterobacteriaceae (CPE) and extensively
      drug-resistant Acinetobacter baumannii (XDR-AB). DESIGN: Before-after
      intervention study. SETTING: Fifteen-bed surgical trauma intensive care unit
      (ICU). METHODS: We investigated the impact of enhanced infection control measures
      in response to clusters of CPE and XDR-AB infections in an ICU from April 2009 to
      March 2010. Polymerase chain reaction was used to detect the presence of blaKPC
      and resistance plasmids in CRE. Pulsed-field gel electrophoresis was performed to
      assess XDR-AB clonality. Enhanced infection-control measures were implemented in
      response to ongoing transmission of CPE and a new outbreak of XDR-AB. Efficacy
      was evaluated by comparing the incidence rate (IR) of CPE and XDR-AB before and
      after the implementation of these measures. RESULTS: The IR of CPE for the 12
      months before the implementation of enhanced measures was 7.77 cases per 1,000
      patient-days, whereas the IR of XDR-AB for the 3 months before implementation was
      6.79 cases per 1,000 patient-days. All examined CPE shared endemic blaKPC
      resistance plasmids, and 6 of the 7 XDR-AB isolates were clonal. Following
      institution of enhanced infection control measures, the CPE IR decreased to 1.22
      cases per 1,000 patient-days (P = .001), and no more cases of XDR-AB were
      identified. CONCLUSIONS: Use of infection control measures described in the
      Centers for Disease Control and Prevention's 2012 CRE toolkit was associated with
      a reduction in the IR of CPE and an interruption in XDR-AB transmission.

PMID- 24915209
TI  - Evaluation of vancomycin-resistant enterococci (VRE)-associated morbidity
      following relaxation of VRE screening and isolation precautions in a tertiary
      care hospital.
AB  - OBJECTIVE: To determine whether relaxing vancomycin-resistant enterococci (VRE)
      precautions results in an increase in the incidence of invasive VRE infections
      over time. DESIGN: Retrospective analysis of a microbiology database before and
      after relaxation of VRE screening and isolation precautions. SETTING: Urban
      tertiary care teaching hospital in Montreal, Canada. PARTICIPANTS: All
      hospitalized and emergency room patients over a 13-year period from January 1,
      2000, to March 31, 2013. METHODS: We assessed the results of all microbiology
      cultures for the presence of VRE as well as the results of all polymerase chain
      reaction assays for vanA and vanB during the study period. Applying criteria for
      4 clinical situations (bacteremia, definite infection, possible infection, and
      colonization with VRE), we analyzed the effects of relaxed VRE screening and
      isolation precautions on the incidence of each of these outcomes over the time
      preceding and following this change. RESULTS: When VRE screening and isolation
      precautions were relaxed, a marked rise in VRE colonization was observed, with a
      lesser but definite rise in the 3 other outcomes. Despite this initial rise in
      all measures, all incidences other than colonization plateaued during the 34
      months of follow-up. CONCLUSIONS: Relaxation of VRE screening and isolation
      precautions was associated with an immediate increase in colonization and
      infection incidence. Despite increasing colonization, infection outcomes remained
      infrequent and stable, suggesting a finite number of susceptible hosts at risk.
      Relaxation of VRE protocols may not lead to increasing infection incidence in a
      hospital setting, advocating that cost effectiveness exercises, with targeted
      screening and isolation precautions, are crucial.

PMID- 24915211
TI  - Survey of infection control practices in hemodialysis units: preventing vascular
      access-associated bloodstream infections.
AB  - OBJECTIVE: Despite surveillance, the Quebec Healthcare-Associated Infections
      Surveillance Program saw no improvement in vascular access-associated bloodstream
      infections in hemodialysis (HD). We aimed to determine the infection control
      measures recommended and implemented in Quebec's HD units, compliance of local
      protocols to infection control practice guidelines, and reasons behind the low
      prevalence of arteriovenous fistulas. METHODS: An online survey was elaborated on
      the basis of the Centers for Disease Control and Prevention (CDC) and National
      Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines. The
      questionnaire was validated (construct, content, face validity, and reliability)
      and sent to all HD units in Quebec (n = 40). Results were analyzed using
      descriptive statistics, linear regression, and Poisson regression. RESULTS:
      Thirty-seven (93%) of 40 HD units participated. Thirty (94%) of the 32 centers
      where central catheters are inserted have written insertion protocols. Compliance
      with practice guidelines is good, except for full-body draping during catheter
      insertion (79%) and ointment use at insertion site (3%). Prevention measures for
      catheter maintenance are in accordance with guidelines, except for skin
      disinfection with at least 0.5% chlorhexidine and 70% alcohol (67% compliance)
      and regular antiseptic ointment use at the insertion site (3%). Before fistula
      cannulation, skin preparation is suboptimal; forearm hygiene is performed in only
      61% of cases. Several factors explain the low rate of fistulas, including patient
      preference (69%) and lack of surgical resources (39%; P = .01). CONCLUSIONS:
      Improvement in standardization of care according to practice guidelines is
      necessary. Fistula rate could be increased by improving access to surgical
      resources and patient education. Strategies are now being elaborated to address
      these findings.

PMID- 24915210
TI  - Preventing surgical site infections: a randomized, open-label trial of nasal
      mupirocin ointment and nasal povidone-iodine solution.
AB  - BACKGROUND: Treatment of Staphylococcus aureus colonization before surgery
      reduces risk of surgical site infection (SSI). The regimen of nasal mupirocin
      ointment and topical chlorhexidine gluconate is effective, but cost and patient
      compliance may be a barrier. Nasal povidone-iodine solution may provide an
      alternative to mupirocin. METHODS: We conducted an investigator-initiated, open
      label, randomized trial comparing SSI after arthroplasty or spine fusion in
      patients receiving topical chlorhexidine wipes in combination with either twice
      daily application of nasal mupirocin ointment during the 5 days before surgery or
      2 applications of povidone-iodine solution into each nostril within 2 hours of
      surgical incision. The primary study end point was deep SSI within the 3 months
      after surgery. RESULTS: In the modified intent-to-treat analysis, a deep SSI
      developed after 14 of 855 surgical procedures in the mupirocin group and 6 of 842
      surgical procedures in the povidone-iodine group (P = .1); S. aureus deep SSI
      developed after 5 surgical procedures in the mupirocin group and 1 surgical
      procedure in the povidone-iodine group (P = .2). In the per protocol analysis, S.
      aureus deep SSI developed in 5 of 763 surgical procedures in the mupirocin group
      and 0 of 776 surgical procedures in the povidone-iodine group (P = .03).
      CONCLUSIONS: Nasal povidone-iodine may be considered as an alternative to
      mupirocin in a multifaceted approach to reduce SSI. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01313182.

PMID- 24915212
TI  - Outpatient parenteral antimicrobial therapy practices among adult infectious
      disease physicians.
AB  - OBJECTIVE: To identify current outpatient parenteral antibiotic therapy practice
      patterns and complications. METHODS: We administered an 11-question survey to
      adult infectious disease physicians participating in the Emerging Infections
      Network (EIN), a Centers for Disease Control and Prevention-sponsored sentinel
      event surveillance network in North America. The survey was distributed
      electronically or via facsimile in November and December 2012. Respondent
      demographic characteristics were obtained from EIN enrollment data. RESULTS:
      Overall, 555 (44.6%) of EIN members responded to the survey, with 450 (81%)
      indicating that they treated 1 or more patients with outpatient parenteral
      antimicrobial therapy (OPAT) during an average month. Infectious diseases
      consultation was reported to be required for a patient to be discharged with OPAT
      by 99 respondents (22%). Inpatient (282 [63%] of 449) and outpatient (232 [52%]
      of 449) infectious diseases physicians were frequently identified as being
      responsible for monitoring laboratory results. Only 26% (118 of 448) had
      dedicated OPAT teams at their clinical site. Few infectious diseases physicians
      have systems to track errors, adverse events, or "near misses" associated with
      OPAT (97 [22%] of 449). OPAT-associated complications were perceived to be rare.
      Among respondents, 80% reported line occlusion or clotting as the most common
      complication (occurring in 6% of patients or more), followed by nephrotoxicity
      and rash (each reported by 61%). Weekly laboratory monitoring of patients who
      received vancomycin was reported by 77% of respondents (343 of 445), whereas 19%
      of respondents (84 of 445) reported twice weekly laboratory monitoring for these
      patients. CONCLUSIONS: Although use of OPAT is common, there is significant
      variation in practice patterns. More uniform OPAT practices may enhance patient
      safety.

PMID- 24915213
TI  - Cost-effectiveness of ensuring hepatitis B protection for previously vaccinated
      healthcare personnel.
AB  - OBJECTIVE: To examine the cost-effectiveness of pre- and postexposure approaches
      for ensuring hepatitis B protection among previously vaccinated healthcare
      personnel (HCP). DESIGN: A decision-analytic model was developed for alternative
      strategies of ensuring hepatitis B protection under assumptions of 68% and 95%
      long-term protection after a primary vaccination series. Costs and quality
      adjusted life years (QALYs) lost from infections were estimated, and incremental
      cost-effectiveness ratios (ICERs) were calculated relative to a no intervention
      alternative over 10 years of intervention. Separate analyses were performed for
      trainees and nontrainees, using the healthcare system perspective. Trainees face
      higher risk of exposure and likely received primary vaccination as infants.
      SETTING: General healthcare settings. PARTICIPANTS: Trainee and nontrainee HCP.
      INTERVENTIONS: Preexposure testing for antibody to hepatitis B surface antigen
      followed by additional vaccination for HCP without protective antibody levels;
      postexposure evaluation and management for HCP reporting blood or body fluid
      exposures RESULTS: The preexposure strategy prevents more infections and has
      higher costs than the postexposure strategy or no intervention. For trainees, 10
      year preexposure evaluation ICERs are $832,875 and $144,457 per QALY for 95% and
      68% long-term vaccine protection, respectively. Trainee 10-year postexposure
      evaluation ICERs are $1,146,660 and $191,579 per QALY under the 95% and 68% long
      term protection assumptions, respectively. For nontrainees, 10-year ICERs are
      $745,739 and $1,129,286 per QALY for the preexposure and postexposure evaluation
      strategies, respectively. CONCLUSIONS: ICERs may inform decision makers as they
      decide whether the added cost of the preexposure strategy provides sufficient
      value in preventing infections.

PMID- 24915214
TI  - Selection of the ideal disinfectant.

PMID- 24915215
TI  - Maintain the gain: program to sustain performance improvement in environmental
      cleaning.
AB  - Sustaining performance is a difficult and often overlooked aspect of quality
      improvement and implementation science. Over a 4-year period, we observed that
      monthly feedback of performance data in face-to-face meetings with frontline
      personnel was crucial in maintaining environmental-cleaning effectiveness in
      adult critical care units. 

PMID- 24915216
TI  - What is the best method? Recovery of methicillin-resistant Staphylococcus aureus
      and extended-spectrum beta-lactamase-producing Escherichia coli from inanimate
      hospital surfaces.
AB  - Environmental sampling in hospitals, when required, needs to be reliable. We
      evaluated different methods of sampling methicillin-resistant Staphylococcus
      aureus and extended-spectrum beta-lactamase-producing Escherichia coli on 5
      materials of the hospital setting. Petrifilms and contact plates were superior to
      swabs for all of the surfaces studied. 

PMID- 24915217
TI  - A comparison of environmental contamination by patients infected or colonized
      with methicillin-resistant Staphylococcus aureus or vancomycin-resistant
      enterococci: a multicenter study.
AB  - A total of 1,023 environmental surfaces were sampled from 45 rooms with patients
      infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) or
      vancomycin-resistant enterococci (VRE) before terminal room cleaning. Colonized
      patients had higher median total target colony-forming units (CFU) of MRSA or VRE
      than did infected patients (median, 25 CFU [interquartile range, 0-106 CFU] vs 0
      CFU [interquartile range, 0-29 CFU]; P = .033). 

PMID- 24915219
TI  - Variable screening and decolonization protocols for Staphylococcus aureus
      carriage prior to surgical procedures.
AB  - We surveyed the Society for Healthcare Epidemiology of America Research Network,
      the Minnesota Association for Professionals in Infection Control and
      Epidemiology, and the Minnesota Hospital Association to assess presurgical
      Staphylococcus aureus screening and decolonization practices. The practices
      varied widely among responding facilities. The majority of respondents (63%) did
      not screen for S. aureus preoperatively. 

PMID- 24915218
TI  - Vancomycin-resistant enterococcus (VRE) transmission and risk factors in contacts
      of VRE carriers.
AB  - During a 2-year period, the vancomycin-resistant enterococcus (VRE) acquisition
      rate was 10.9% (40/368) in patients who had shared a room with a newly detected
      VRE carrier. Exposure to vancomycin and to anti-anaerobic antibiotics were
      identified as independent risk factors for VRE acquisition. Sensitivity of the
      first rectal VRE screening was less than 50%. 

PMID- 24915220
TI  - Efficacy of a washer-disinfector in eliminating healthcare-associated pathogens
      from surgical instruments.
AB  - This study was designed to test the efficacy of a washer-disinfector in
      eliminating selected healthcare-associated pathogens from surgical instruments.
      Our results showed that a washer-disinfector was extremely effective in
      eliminating microorganisms (>7-log(10) reduction), including vegetative and spore
      forming bacteria, from experimentally contaminated instruments. The washer
      disinfector remained effective in eliminating microorganisms in the absence of
      enzymatic cleaners and detergents.

PMID- 24915221
TI  - An automated algorithm to preselect patients to be assessed individually in point
      prevalence surveys for hospital-acquired infections in surgery.
AB  - In this pilot study, we evaluate an algorithm that uses predictive clinical and
      laboratory parameters to differentiate between patients with hospital-acquired
      infection (HAI) and patients without HAI. Seventy-four percent of the studied
      population of surgical patients could be reliably (negative predictive value of
      98%) excluded from detailed assessment by the infection control practitioner. 

PMID- 24915222
TI  - Evaluation of an algorithm for electronic surveillance of hospital-acquired
      infections yielding serial weekly point prevalence scores.
AB  - Surveillance of hospital-acquired infections can be approximated by repeated
      surveys that are performed in a standardized, cost-effective manner. We developed
      an integrated software system for serial electronic hospital-wide point
      prevalence surveys using algorithms that proved highly sensitive and specific
      over a 5-year period in a large university medical center. 

PMID- 24915223
TI  - Survey of infection prevention informatics use and practitioner satisfaction in
      US hospitals.
AB  - We surveyed hospital epidemiologists and infection preventionists on their usage
      of and satisfaction with infection prevention-specific software supplementing
      their institution's electronic medical record. Respondents with supplemental
      software were more satisfied with their software's infection prevention and
      antimicrobial stewardship capabilities than those without. Infection
      preventionists were more satisfied than hospital epidemiologists. 

PMID- 24915224
TI  - Effectiveness of common healthcare disinfectants against H1N1 influenza virus on
      reusable elastomeric respirators.
AB  - This study evaluated the efficacy of 3 common hospital disinfectants to
      inactivate influenza virus on elastomeric respirators. Quaternary
      ammonium/isopropyl alcohol and bleach detergent wipes eliminated live virus,
      whereas 70% isopropyl alcohol alone was ineffective. 

PMID- 24915225
TI  - On-site availability of Legionella testing in acute care hospitals, United
      States.
AB  - We surveyed 399 US acute care hospitals regarding availability of on-site
      Legionella testing; 300 (75.2%) did not offer Legionella testing on site.
      Availability varied according to hospital size and geographic location. On-site
      access to testing may improve detection of Legionnaires disease and inform
      patient management and prevention efforts. 

PMID- 24915226
TI  - The prediction of complicated Clostridium difficile infections in children.
AB  - We validated proposed definitions for severe Clostridium difficile infection
      (CDI) in adults for prediction of complicated CDI in children. Complicated CDI
      occurred in 9 of 202 cases. Definitions for severe CDI in adults showed poor
      measures for discrimination of complicated CDI in children, which calls into
      question the usefulness of such definitions in pediatric cohorts. 

PMID- 24915227
TI  - Pediatric Clostridium difficile infection: 6-year active surveillance in a
      defined patient population.

PMID- 24915228
TI  - Managing the consequences of neurosurgical intervention in a patient with
      previously undiagnosed Creutzfeldt-Jakob disease.

PMID- 24915229
TI  - Reply to Smyth et al.

PMID- 24915230
TI  - Antibiotic burden associated with treatment of asymptomatic bacteriuria.

PMID- 24915231
TI  - Hospital Clostridium difficile infection testing rates: is "don't ask, don't
      tell" at play?

PMID- 24915233
TI  - Synergistic effect on corrosion resistance of Phynox substrates grafted with
      surface-initiated ATRP (co)polymerization of 2-methacryloyloxyethyl
      phosphorylcholine (MPC) and 2-hydroxyethyl methacrylate (HEMA).
AB  - Phynox is of high interest for biomedical applications due to its
      biocompatibility and corrosion resistance. However, some Phynox applications
      require specific surface properties. These can be imparted with suitable surface
      functionalizations of its oxide layer. The present work investigates the surface
      initiated atom transfer radical polymerization (ATRP) of 2-methacryloyoxyethyl
      phosphorylcholine (MPC), 2-hydroxyethyl methacrylate (HEMA), and ATRP
      copolymerization of (HEMA-co-MPC) (block and statistic copolymerization with
      different molar ratios) on grafted Phynox substrates modified with 11-(2
      bromoisobutyrate)-undecyl-1-phosphonic acid (BUPA) as initiator. It is found that
      ATRP (co)polymerization of these monomers is feasible and forms hydrophilic
      layers, while improving the corrosion resistance of the system. 

PMID- 24915234
TI  - Temperature induced morphological transitions from native to unfolded aggregated
      States of human serum albumin.
AB  - The circulatory protein, human serum albumin (HSA), is known to have two melting
      point temperatures, 56 and 62  degrees C. In this present manuscript, we
      investigate the interaction of HSA with a synthesized bioactive molecule 3
      pyrazolyl 2-pyrazoline (PZ). The sole tryptophan amino acid residue (Trp214) of
      HSA and PZ forms an excellent FRET pair and has been used to monitor the
      conformational dynamics in HSA as a function of temperature. Molecular docking
      studies reveal that the PZ binds to a site which is in the immediate vicinity of
      Trp214, and such data are also supported by time-resolved FRET studies. Steady
      state and time-resolved anisotropy of PZ conclusively proved that the structural
      and morphological changes in HSA mainly occur beyond its first melting
      temperature. Although the protein undergoes thermal denaturation at elevated
      temperatures, the Trp214 gets buried inside the protein scaffolds; this fact has
      been substantiated by acrylamide quenching studies. Finally, we have used atomic
      force microscopy to establish that at around 70  degrees C, HSA undergoes self
      assembly to form fibrillar structures. Such an observation may be attributed to
      the loss of alpha-helical content of the protein and a subsequent rise in beta
      sheet structure. 

PMID- 24915235
TI  - Mesalamine-induced myopericarditis in a paediatric patient with Crohn's disease.
AB  - Mesalamine-containing products are considered first-line treatment for
      inflammatory bowel disease. Myocarditis is recognised as a very rare possible
      side effect of these medications, but has not often been described in the
      paediatric population. We present a case of an adolescent with Crohn's disease
      who presented with myopericarditis after recent initiation of Pentasa. Once
      identified as the causative agent, the drug was discontinued, with subsequent
      normalisation of troponin and improvement of function. This case identifies the
      importance of prompt evaluation, diagnosis, and treatment of paediatric patients
      receiving mesalamine-containing medications that present with significant
      cardiovascular symptoms. 

PMID- 24915236
TI  - Luna, a Drosophila KLF6/KLF7, is maternally required for synchronized nuclear and
      centrosome cycles in the preblastoderm embryo.
AB  - Kruppel like factors (KLFs) are conserved transcription factors that have been
      implicated in many developmental processes including differentiation, organ
      patterning, or regulation of stem cell pluripotency. We report the generation and
      analysis of loss-of-function mutants of Drosophila Klf6/7, the luna gene. We
      demonstrate that luna mutants are associated with very early embryonic defects
      prior to cellularization at the syncytial stage and cause DNA separation defects
      during the rapid mitotic cycles resulting in un-coupled DNA and centrosome
      cycles. These defects manifest themselves, both in animals that are maternally
      homozygous and heterozygous mutant. Surprisingly, luna is only required during
      the syncytial stages and not later in development, suggesting that the DNA
      segregation defect is linked to centrosomes, since centrosomes are dispensable
      for later cell divisions. 

PMID- 24915237
TI  - Interaction effects of long-term air pollution exposure and variants in the
      GSTP1, GSTT1 and GSTCD genes on risk of acute myocardial infarction and
      hypertension: a case-control study.
AB  - INTRODUCTION: Experimental and epidemiological studies have reported associations
      between air pollution exposure, in particular related to vehicle exhaust, and
      cardiovascular disease. A potential pathophysiological pathway is pollution
      induced pulmonary oxidative stress, with secondary systemic inflammation. Genetic
      polymorphisms in genes implicated in oxidative stress, such as GSTP1, GSTT1 and
      GSTCD, may contribute to determining individual susceptibility to air pollution
      as a promoter of coronary vulnerability. AIMS: We aimed to investigate effects of
      long-term traffic-related air pollution exposure, as well as variants in GSTP1,
      GSTT1 and GSTCD, on risk of acute myocardial infarction (AMI) and hypertension.
      In addition, we studied whether air pollution effects were modified by the
      investigated genetic variants. METHODS: Genotype data at 7 single nucleotide
      polymorphisms (SNPs) in the GSTP1 gene, and one in each of the GSTT1 and GSTCD
      genes, as well as air pollution exposure estimates, were available for 119 AMI
      cases and 1310 randomly selected population controls. Population control
      individuals with systolic blood pressure >=140 mmHg, diastolic blood pressure
      >=90 mmHg or on daily antihypertensive medication were defined as hypertensive (n
      = 468). Individual air pollution exposure levels were modeled as annual means of
      NO2 (marker of vehicle exhaust pollutants) using central monitoring data and
      dispersion models, linking to participants' home addresses. RESULTS: Air
      pollution was significantly associated with risk of AMI: OR 1.78 (95%CI 1.04
      3.03) per 10 ug/m3 of long-term NO2 exposure. Three GSTP1 SNPs were significantly
      associated with hypertension. The effect of air pollution on risk of AMI varied
      by genotype strata, although the suggested interaction was not significant. We
      saw no obvious interaction between genetic variants in the GST genes and air
      pollution exposure for hypertension. CONCLUSION: Air pollution exposure entails
      an increased risk of AMI, and this risk differed over genotype strata for
      variants in the GSTP1, GSTT1 and GSTCD genes, albeit not statistically
      significantly.

PMID- 24915238
TI  - Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in
      Swedish population.
AB  - A complex interplay between genetic and environmental factors is thought to be
      involved in the etiology of Parkinson's disease (PD). A recent genome-wide
      association and interaction study (GWAIS) identified GRIN2A, which encodes an
      NMDA-glutamate-receptor subunit involved in brain's excitatory neurotransmission,
      as a PD genetic modifier in inverse association with caffeine intake. Here in, we
      attempted to replicate the reported association of a single nucleotide
      polymorphism, GRIN2A_rs4998386, and its interaction with caffeine intake with PD
      in patient-control study in an ethnically homogenous population in southeastern
      Sweden, as consistent and independent genetic association studies are the gold
      standard for the validation of genome-wide association studies. All the subjects
      (193 sporadic PD patients and 377 controls) were genotyped, and the caffeine
      intake data was obtained by questionnaire. We observed an association between
      rs4998386 and PD with odds ratio (OR) of 0.61, 95% confidence intervals (CI) of
      0.39-0.96, p = 0.03, under a model excluding rare TT allele. There was also a
      strong significance in joint effects of gene and caffeine on PD risk (TC heavy
      caffeine vs. CC light caffeine: OR = 0.38, 95%CI = [0.20-0.70], p = 0.002) and
      gene-caffeine interaction (OR = 0.998, 95%CI = [0.991-0.999], p<0.001). Overall,
      our results are in support of the findings of the GWAIS and provided additional
      evidence indicating PD protective effects of coffee drinking/caffeine intake as
      well as the interaction with glutamate receptor genotypes.

PMID- 24915241
TI  - Maudell Sleet's Magic Garden: Romare Bearden.

PMID- 24915242
TI  - WHO issues guidelines on HCV amid drug cost controversy.

PMID- 24915243
TI  - Physical activity may stave off diabetes for women at risk.

PMID- 24915253
TI  - Addressing the burden of diabetes.

PMID- 24915254
TI  - Revolution to a new standard treatment of diabetic macular edema.

PMID- 24915255
TI  - Interpretation of hemoglobin A1c values.

PMID- 24915256
TI  - A piece of my mind. Whose story is it, anyway?

PMID- 24915257
TI  - Comparative effectiveness research and outcomes of diabetes treatment.

PMID- 24915258
TI  - Controlling the metabolic roller coaster in diabetes.

PMID- 24915260
TI  - Association between intensification of metformin treatment with insulin vs
      sulfonylureas and cardiovascular events and all-cause mortality among patients
      with diabetes.
AB  - IMPORTANCE: Preferred second-line medication for diabetes treatment after
      metformin failure remains uncertain. OBJECTIVE: To compare time to acute
      myocardial infarction (AMI), stroke, or death in a cohort of metformin initiators
      who added insulin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective cohort constructed with national Veterans Health Administration,
      Medicare, and National Death Index databases. The study population comprised
      veterans initially treated with metformin from 2001 through 2008 who subsequently
      added either insulin or sulfonylurea. Propensity score matching on
      characteristics was performed, matching each participant who added insulin to 5
      who added a sulfonylurea. Patients were followed through September 2011 for
      primary analyses or September 2009 for cause-of-death analyses. MAIN OUTCOMES AND
      MEASURES: Risk of a composite outcome of AMI, stroke hospitalization, or all
      cause death was compared between therapies with marginal structural Cox
      proportional hazard models adjusting for baseline and time-varying demographics,
      medications, cholesterol level, hemoglobin A1c level, creatinine level, blood
      pressure, body mass index, and comorbidities. RESULTS: Among 178,341 metformin
      monotherapy patients, 2948 added insulin and 39,990 added a sulfonylurea.
      Propensity score matching yielded 2436 metformin + insulin and 12,180 metformin +
      sulfonylurea patients. At intensification, patients had received metformin for a
      median of 14 months (IQR, 5-30), and hemoglobin A1c level was 8.1% (IQR, 7.2%
      9.9%). Median follow-up after intensification was 14 months (IQR, 6-29 months).
      There were 172 vs 634 events for the primary outcome among patients who added
      insulin vs sulfonylureas, respectively (42.7 vs 32.8 events per 1000 person
      years; adjusted hazard ratio [aHR], 1.30; 95% CI, 1.07-1.58; P = .009). Acute
      myocardial infarction and stroke rates were statistically similar, 41 vs 229
      events (10.2 and 11.9 events per 1000 person-years; aHR, 0.88; 95% CI, 0.59-1.30;
      P = .52), whereas all-cause death rates were 137 vs 444 events, respectively
      (33.7 and 22.7 events per 1000 person-years; aHR, 1.44; 95% CI, 1.15-1.79; P =
      .001). There were 54 vs 258 secondary outcomes: AMI, stroke hospitalizations, or
      cardiovascular deaths (22.8 vs 22.5 events per 1000 person-years; aHR, 0.98; 95%
      CI, 0.71-1.34; P = .87). CONCLUSIONS AND RELEVANCE: Among patients with diabetes
      who were receiving metformin, the addition of insulin vs a sulfonylurea was
      associated with an increased risk of a composite of nonfatal cardiovascular
      outcomes and all-cause mortality. These findings require further investigation to
      understand risks associated with insulin use in these patients.

PMID- 24915261
TI  - Association of bariatric surgery with long-term remission of type 2 diabetes and
      with microvascular and macrovascular complications.
AB  - IMPORTANCE: Short-term studies show that bariatric surgery causes remission of
      diabetes. The long-term outcomes for remission and diabetes-related complications
      are not known. OBJECTIVES: To determine the long-term diabetes remission rates
      and the cumulative incidence of microvascular and macrovascular diabetes
      complications after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS: The
      Swedish Obese Subjects (SOS) is a prospective matched cohort study conducted at
      25 surgical departments and 480 primary health care centers in Sweden. Of
      patients recruited between September 1, 1987, and January 31, 2001, 260 of 2037
      control patients and 343 of 2010 surgery patients had type 2 diabetes at
      baseline. For the current analysis, diabetes status was determined at SOS health
      examinations until May 22, 2013. Information on diabetes complications was
      obtained from national health registers until December 31, 2012. Participation
      rates at the 2-, 10-, and 15-year examinations were 81%, 58%, and 41% in the
      control group and 90%, 76%, and 47% in the surgery group. For diabetes
      assessment, the median follow-up time was 10 years (interquartile range [IQR], 2
      15) and 10 years (IQR, 10-15) in the control and surgery groups, respectively.
      For diabetes complications, the median follow-up time was 17.6 years (IQR, 14.2
      19.8) and 18.1 years (IQR, 15.2-21.1) in the control and surgery groups,
      respectively. INTERVENTIONS: Adjustable or nonadjustable banding (n = 61),
      vertical banded gastroplasty (n = 227), or gastric bypass (n = 55) procedures
      were performed in the surgery group, and usual obesity and diabetes care was
      provided to the control group. MAIN OUTCOMES AND MEASURES: Diabetes remission,
      relapse, and diabetes complications. Remission was defined as blood glucose <110
      mg/dL and no diabetes medication. RESULTS: The diabetes remission rate 2 years
      after surgery was 16.4% (95% CI, 11.7%-22.2%; 34/207) for control patients and
      72.3% (95% CI, 66.9%-77.2%; 219/303) for bariatric surgery patients (odds ratio
      [OR], 13.3; 95% CI, 8.5-20.7; P < .001). At 15 years, the diabetes remission
      rates decreased to 6.5% (4/62) for control patients and to 30.4% (35/115) for
      bariatric surgery patients (OR, 6.3; 95% CI, 2.1-18.9; P < .001). With long-term
      follow-up, the cumulative incidence of microvascular complications was 41.8 per
      1000 person-years (95% CI, 35.3-49.5) for control patients and 20.6 per 1000
      person-years (95% CI, 17.0-24.9) in the surgery group (hazard ratio [HR], 0.44;
      95% CI, 0.34-0.56; P < .001). Macrovascular complications were observed in 44.2
      per 1000 person-years (95% CI, 37.5-52.1) in control patients and 31.7 per 1000
      person-years (95% CI, 27.0-37.2) for the surgical group (HR, 0.68; 95% CI, 0.54
      0.85; P = .001). CONCLUSIONS AND RELEVANCE: In this very long-term follow-up
      observational study of obese patients with type 2 diabetes, bariatric surgery was
      associated with more frequent diabetes remission and fewer complications than
      usual care. These findings require confirmation in randomized trials. TRIAL
      REGISTRATION clinicaltrials.gov Identifier: NCT01479452.

PMID- 24915264
TI  - Diabetes overtreatment in elderly individuals: risky business in need of better
      management.

PMID- 24915263
TI  - Insulin therapy for type 2 diabetes mellitus.
AB  - IMPORTANCE: The incidence and prevalence of type 2 diabetes mellitus are
      increasing. OBJECTIVE: To review currently available insulin therapy, as well as
      evidence on the use, application, initiation, and intensification of insulin in
      the outpatient setting. EVIDENCE REVIEW: Data sources included PubMed for trials
      and investigations in type 2 diabetes examining insulin use from January 1998 to
      April 2014. FINDINGS: The hemoglobin A1c target for most patients with type 2
      diabetes is 7% but needs to be modified when there is increased risk of
      hypoglycemia, reduced life expectancy, extensive comorbidities, or reduced
      resources. Insulin therapy may be considered early or late in the disease course;
      adverse effects include weight gain and hypoglycemia. Basal insulin can be added
      to oral hypoglycemic agents (generally stopping sulfonylureas) initially, and
      later, prandial insulin can be added in a stepwise fashion. Insulin treatment
      must be individualized, and there are a number of challenges to insulin
      initiation and intensification. CONCLUSIONS AND RELEVANCE: Insulin can help
      achieve ideal hemoglobin A1c goals for patients with type 2 diabetes. Barriers
      such as adherence, patient preferences, clinician preferences, and resource
      allocation must be addressed.

PMID- 24915265
TI  - A solitary red patch.

PMID- 24915266
TI  - Use and out-of-pocket costs of insulin for type 2 diabetes mellitus from 2000
      through 2010.

PMID- 24915267
TI  - Antihypertensive therapy after acute ischemic stroke.

PMID- 24915268
TI  - Antihypertensive therapy after acute ischemic stroke.

PMID- 24915262
TI  - Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino
      population.
AB  - IMPORTANCE: Latino populations have one of the highest prevalences of type 2
      diabetes worldwide. OBJECTIVES: To investigate the association between rare
      protein-coding genetic variants and prevalence of type 2 diabetes in a large
      Latino population and to explore potential molecular and physiological mechanisms
      for the observed relationships. DESIGN, SETTING, AND PARTICIPANTS: Whole-exome
      sequencing was performed on DNA samples from 3756 Mexican and US Latino
      individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from
      1993 to 2013. One variant was further tested for allele frequency and association
      with type 2 diabetes in large multiethnic data sets of 14,276 participants and
      characterized in experimental assays. MAIN OUTCOME AND MEASURES: Prevalence of
      type 2 diabetes. Secondary outcomes included age of onset, body mass index, and
      effect on protein function. RESULTS: A single rare missense variant (c.1522G>A
      [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48;
      95% CI, 2.83-10.61; P = 4.4 * 10(-7)) in hepatocyte nuclear factor 1-alpha
      (HNF1A), the gene responsible for maturity onset diabetes of the young type 3
      (MODY3). This variant was observed in 0.36% of participants without type 2
      diabetes and 2.1% of participants with it. In multiethnic replication data sets,
      the p.E508K variant was seen only in Latino patients (n = 1443 with type 2
      diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16;
      95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding
      the p.E508K mutant demonstrated reduced transactivation activity of its target
      promoter compared with a wild-type protein. In our data, carriers and noncarriers
      of the p.E508K mutation with type 2 diabetes had no significant differences in
      compared clinical characteristics, including age at onset. The mean (SD) age for
      carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and
      the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P =
      .19). CONCLUSIONS AND RELEVANCE: Using whole-exome sequencing, we identified a
      single low-frequency variant in the MODY3-causing gene HNF1A that is associated
      with type 2 diabetes in Latino populations and may affect protein function. This
      finding may have implications for screening and therapeutic modification in this
      population, but additional studies are required.

PMID- 24915269
TI  - Antihypertensive therapy after acute ischemic stroke--reply.

PMID- 24915270
TI  - Left atrial fibrosis and recurrent arrhythmia.

PMID- 24915271
TI  - Left atrial fibrosis and recurrent arrhythmia--reply.

PMID- 24915272
TI  - Economic incentives and use of the intensive care unit.

PMID- 24915276
TI  - Economic incentives and use of the intensive care unit--reply.

PMID- 24915278
TI  - The changing theories of diabetes.

PMID- 24915279
TI  - JAMA patient page. Starting insulin treatment for diabetes.

PMID- 24915280
TI  - Well-defined all-conducting block copolymer bilayer hybrid nanostructure:
      selective positioning of lithium ions and efficient charge collection.
AB  - A block copolymerization of nonfunctionalized conducting monomers was developed
      to enable the successful synthesis of a highly insoluble 3,4
      (ethylenedioxy)thienyl-based all-conducting block copolymer (PEDOT-b-PEDOT-TB)
      that could encapsulate nanocrystalline dyed TiO2 particles, resulting in the
      formation of an all-conducting block copolymer bilayer hybrid nanostructure
      (TiO2/Dye/PEDOT-b-PEDOT-TB). Lithium ions were selectively positioned on the
      outer PEDOT-TB surface. The distances through which the positively charged dye
      and PEDOT-TB(Li(+)) interacted physically or through which the TiO2 electrode and
      the Li(+) centers on PEDOT-TB(Li(+)) interacted ionically were precisely tuned
      and optimized within ca. 1 nm by controlling the thickness of the PEDOT blocking
      layer (the block length). The optimized structure provided efficient charge
      collection in an iodine-free dye-sensitized solar cell (DSC) due to negligible
      recombination of photoinduced electrons with cationic species and rapid charge
      transport, which improved the photovoltaic performance (eta = 2.1 -> 6.5%). 

PMID- 24915259
TI  - Hydrolyzed infant formula and early beta-cell autoimmunity: a randomized clinical
      trial.
AB  - IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts
      during the first years of life. Early exposure to complex dietary proteins may
      increase the risk of beta-cell autoimmunity in children at genetic risk for type
      1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.
      OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed
      formula decreases the cumulative incidence of diabetes-associated autoantibodies
      in young children. DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized
      clinical trial of 2159 infants with HLA-conferred disease susceptibility and a
      first-degree relative with type 1 diabetes recruited from May 2002 to January
      2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to
      the extensively hydrolyzed casein formula and 1081 were randomized to be weaned
      to a conventional cows' milk-based formula. The participants were observed to
      April 16, 2013. INTERVENTIONS: The participants received either a casein
      hydrolysate or a conventional cows' milk formula supplemented with 20% of the
      casein hydrolysate. MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity
      for at least 2 diabetes-associated autoantibodies out of 4 analyzed.
      Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma
      associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet
      cell antibodies with immunofluorescence during a median observation period of 7.0
      years (mean, 6.3 years). RESULTS: The absolute risk of positivity for 2 or more
      islet autoantibodies was 13.4% among those randomized to the casein hydrolysate
      formula (n = 139) vs 11.4% among those randomized to the conventional formula (n
      = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies
      among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI,
      0.94-1.54), compared with those randomized to the conventional formula, while the
      hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use,
      study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58).
      There were no clinically significant differences in the rate of reported adverse
      events between the 2 groups. CONCLUSIONS AND RELEVANCE: Among infants at risk for
      type 1 diabetes, the use of a hydrolyzed formula, when compared with a
      conventional formula, did not reduce the incidence of diabetes-associated
      autoantibodies after 7 years. These findings do not support a benefit from
      hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier:
      NCT00179777.

PMID- 24915281
TI  - Limited reversibility of bioconcentration of hydrophobic organic chemicals in
      phytoplankton.
AB  - Aging, reversibility, and desorption rates for the binding of hydrophobic
      chemicals (HOC) to phytoplankton cells have not been directly measured. Here the
      effect of bioconcentration time on subsequent desorption of hexachlorobenzene
      (HCB) and polychlorinated biphenyls (PCBs) was studied for the alga Monoraphidium
      minutum. Cell suspensions were exposed to HCB and PCBs spanning a range of log
      Kow values of 5.7 to 8.2, for 0.13 to 14 d. Subsequently, reversibility and
      desorption rates were assessed by extracting the chemicals from the cells using
      infinite sink extractions with Tenax beads or Empore disks employed in the cell
      suspension. Uptake was biphasic with constant relative contributions of fast
      surface sorption. Desorption was biphasic too and well fitted to a first order
      two compartment model. Increasing exposure times resulted in increasing slowly
      desorbing chemical fractions and decreased desorption rates from these fractions.
      For the most hydrophobic PCBs, slowly desorbing fractions were >80-90%, whereas
      desorption half-lives from these fractions ranged up to 120 days. The slow
      desorption rates directly prove that bioconcentration to algae can be rate
      limited and imply that already after a few hours of exposure, HOCs may become
      practically unavailable for repartitioning. 

PMID- 24915283
TI  - Molecular characterization of diverse species enterovirus-B types from children
      with acute flaccid paralysis and asymptomatic children in Nigeria.
AB  - Non-polio enteroviruses (NPEVs) have often been identified in association with
      acute flaccid paralysis (AFP) in most polio surveillance studies worldwide. In a
      polio endemic country like Nigeria, there is need for distinction of AFP due to
      poliovirus and those potentially due to NPEVs. This study was undertaken to
      characterize the enterovirus (EV) types circulating in both children with and
      without AFP in Nigeria. Of fecal sample from 966 children with AFP, 96 (10%) were
      positive for NPEVs in RD cells, while 42 (5.5%) of 756 samples from non-AFP
      children was positive. Genotyping of all NPEV isolates was done by partial VP1
      gene sequencing and phylogenetic analysis. EV-B was the predominant species
      detected (84%) and infection was common in children with AFP with CVB3, E6, and
      E11 constituting the predominant types detected. The CVB3 isolates cluster with
      Chinese CVB3 isolate recently detected in a newborn with AFP. There was also a
      remarkable clustering of isolates such as E6, E12, E13, E24, E30 and E33 to types
      previous detected in West Africa suggesting a probable circulation of these
      lineages in the region. Taken together, this study reveals a diverse species EV-B
      types in AFP cases and highlights the fact that other neurotropic EVs circulate
      in asymptomatic persons. Improved continuous surveillance of NPEV is warranted as
      in the likely attainment of polio eradication, other neurotropic EVs may emerge
      causing similar paralytic diseases. 

PMID- 24915284
TI  - Biomedical studies on temporal bones of the first multi-channel cochlear implant
      patient at the University of Melbourne.
AB  - OBJECTIVE: To analyse the temporal bones and implant of the first University of
      Melbourne's (UOM) patient (MC-1) to receive the multi-channel cochlear
      prosthesis. METHODS: The left cochlea was implanted with the prototype multi
      channel cochlear prosthesis on 1 August 1978, and the Cochlear versions CI-22 and
      CI-24 on 22 June 1983 and 10 November 1998, respectively. MC-1 died in 2007.
      RESULTS: Plain X-rays of the temporal bones showed that after the CI-22 had been
      explanted seven electrode bands remained in situ. Micro-CT scans also revealed a
      partially united fracture transecting the left implanted and right control
      cochleae. Histology indicated a total loss of the organ of Corti on both sides,
      and a tear of the left basilar membrane. In addition, there was a dense fibrous
      capsule with heterotopic bone surrounding one proximal band of the CI-22 array
      that restricted its removal. This pathology was associated with dark particulate
      material within macrophages, probably due to the release of platinum from the
      electrode bands. Scanning electron microscopy (SEM) showed possible corrosion of
      platinum and surface roughening. Three-dimensional reconstruction of the cochlear
      histology demonstrated the position of the electrode tracts (C1-22 and CI-24) in
      relation to the spiral ganglion, which showed 85-90% loss of ganglion cells.
      DISCUSSION AND CONCLUSIONS: This study confirms our first histopathological
      findings that our first free-fitting banded electrode array produced moderate
      trauma to the cochlea when inserted around the scala tympani of the basal turn.
      The difficulty in extraction was most likely due to one band being surrounded by
      an unusually large amount of fibrous tissue and bone, with an electrode band
      caught due to surface irregularities. Some surface corrosion and a small degree
      of platinum deposition in the tissue may also help explain the outcome for this
      long-term cochlear implantation.

PMID- 24915285
TI  - Addition of a second binding site increases the dynamic range but alters the
      cellular localization of a red fluorescent probe for mobile zinc.
AB  - We report the synthesis and photophysical properties of ZBR4 and ZR1, two
      resorufin-based ditopic probes for mobile zinc. Upon binding Zn(2+), the sensors
      display 14- and 41-fold enhancements of their red fluorescence emission,
      respectively. In contrast to ZR1 and other members of the ZBR family, which
      accumulate in the endoplasmic reticulum, ZBR4 spontaneously localizes to the
      mitochondria of HeLa cells. The modular approach in designing the constructs
      facilitates a homologation strategy aimed at tuning the zinc-binding and
      intracellular targeting properties of future probes. 

PMID- 24915282
TI  - Single aromatic residue location alters nucleic acid binding and chaperone
      function of FIV nucleocapsid protein.
AB  - Feline immunodeficiency virus (FIV) is a retrovirus that infects domestic cats,
      and is an excellent animal model for human immunodeficiency virus type 1 (HIV-1)
      pathogenesis. The nucleocapsid (NC) protein is critical for replication in both
      retroviruses. FIV NC has several structural features that differ from HIV-1 NC.
      While both NC proteins have a single conserved aromatic residue in each of the
      two zinc fingers, the aromatic residue on the second finger of FIV NC is located
      on the opposite C-terminal side relative to its location in HIV-1 NC. In
      addition, whereas HIV-1 NC has a highly charged cationic N-terminal tail and a
      relatively short C-terminal extension, the opposite is true for FIV NC. To probe
      the impact of these differences on the nucleic acid (NA) binding and chaperone
      properties of FIV NC, we carried out ensemble and single-molecule assays with
      wild-type (WT) and mutant proteins. The ensemble studies show that FIV NC binding
      to DNA is strongly electrostatic, with a higher effective charge than that
      observed for HIV-1 NC. The C-terminal basic domain contributes significantly to
      the NA binding capability of FIV NC. In addition, the non-electrostatic component
      of DNA binding is much weaker for FIV NC than for HIV-1 NC. Mutation of both
      aromatic residues in the zinc fingers to Ala (F12A/W44A) further increases the
      effective charge of FIV NC and reduces its non-electrostatic binding affinity.
      Interestingly, switching the location of the C-terminal aromatic residue to mimic
      the HIV-1 NC sequence (N31W/W44A) reduces the effective charge of FIV NC and
      increases its non-electrostatic binding affinity to values similar to HIV-1 NC.
      Consistent with the results of these ensemble studies, single-molecule DNA
      stretching studies show that while WT FIV NC has reduced stacking capability
      relative to HIV-1 NC, the aromatic switch mutant recovers the ability to
      intercalate between the DNA bases. Our results demonstrate that altering the
      position of a single aromatic residue switches the binding mode of FIV NC from
      primarily electrostatic binding to more non-electrostatic binding, conferring
      upon it NA interaction properties comparable to that of HIV-1 NC. 

PMID- 24915286
TI  - Nanoparticle (star polymer) delivery of nitric oxide effectively negates
      Pseudomonas aeruginosa biofilm formation.
AB  - Biofilms are increasingly recognized as playing a major role in human infectious
      diseases, as they can form on both living tissues and abiotic surfaces, with
      serious implications for applications that rely on prolonged exposure to the body
      such as implantable biomedical devices or catheters. Therefore, there is an
      urgent need to develop improved therapeutics to effectively eradicate unwanted
      biofilms. Recently, the biological signaling molecule nitric oxide (NO) was
      identified as a key regulator of dispersal events in biofilms. In this paper, we
      report a new class of core cross-linked star polymers designed to store and
      release nitric oxide, in a controlled way, for the dispersion of biofilms. First,
      core cross-linked star polymers were prepared by reversible addition
      fragmentation chain transfer polymerization (RAFT) via an arm first approach.
      Poly(oligoethylene methoxy acrylate) chains were synthesized by RAFT
      polymerization, and then chain extended in the presence of 2-vinyl-4,4-dimethyl-5
      oxazolone monomer (VDM) with N,N-methylenebis(acrylamide) employed as a cross
      linker to yield functional core cross-linked star polymers. Spermine was
      successfully attached to the star core by reaction with VDM. Finally, the
      secondary amine groups were reacted with NO gas to yield NO-core cross-linked
      star polymers. The core cross-linked star polymers were found to release NO in a
      controlled, slow delivery in bacterial cultures showing great efficacy in
      preventing both cell attachment and biofilm formation in Pseudomonas aeruginosa
      over time via a nontoxic mechanism, confining bacterial growth to the suspended
      liquid. 

PMID- 24915288
TI  - Sedentary behaviour and adiposity in elite athletes.
AB  - Overweight and obesity are defined as abnormal or excessive fat accumulation that
      presents a health risk. Even in athletes an increased adiposity affects health
      and performance. Sedentary behaviour has been associated with higher levels of
      adiposity, independent of moderate-to-vigorous physical activity. However, it is
      unclear whether this independent relationship still exists in highly trained
      athletes. The aim of this study was to examine the association of sedentary
      behaviour with body fatness in elite athletes. Cross-sectional data from 82 male
      athletes (mean age 22 years) were used. Total and regional body composition was
      measured by dual energy X-ray absorptiometry. Self-reported time spent in
      sedentary behaviour and weekly training time was assessed in all participants at
      one time point and multiple regression analyses were used. Sedentary behaviour
      predicted total fat mass (beta = 0.77; 95% CI: 0.36-1.19, P < 0.001) and trunk
      fat mass (beta = 0.25; 95% CI: 0.07-0.43, P = 0.007), independent of age, weekly
      training time, and residual mass (calculated as weight-dependent variable) but
      not abdominal fat. Also, no associations of sedentary behaviour with fat-free
      mass, appendicular lean soft tissue, and body mass index were found. These
      findings indicate that athletes with higher amounts of sedentary behaviour
      presented higher levels of total and trunk fatness, regardless of age, weekly
      training time, and residual mass. Therefore, even high moderate-to-vigorous
      physical activity levels do not mitigate the associations between sedentary
      behaviour and body fatness in highly trained athletes.

PMID- 24915289
TI  - Component-resolved diagnostic of cow's milk allergy by immunoaffinity capillary
      electrophoresis-matrix assisted laser desorption/ionization mass spectrometry.
AB  - Component-resolved diagnostic (CRD) of cow's milk allergy has been performed
      using immunoaffinity capillary electrophoresis (IACE) coupled with matrix
      assisted laser desorption/ionization mass spectrometry (MALDI MS). First, total
      IgE quantification in the blood serum of a milk allergic patient by the IACE-UV
      technique was developed using magnetic beads (MBs) coated with antihuman IgE
      antibodies (Abs) to perform the general allergy diagnosis. Then, the
      immunocomplex of antihuman IgE Abs with the patient IgE Abs, obtained during the
      total IgE analysis, was chemically cross-linked on the MBs surface. Prepared
      immunosupport was used for the binding of individual milk allergens to identify
      the proteins triggering the allergy by IACE with UV and MALDI MS detection. Then,
      allergy CRD was also performed directly with milk fractions. Bovine serum
      albumin, lactoferrin, and alpha-casein (S1 and S2 forms, as was revealed by MALDI
      MS) were found to bind with the extracted IgE Abs, indicating that the chosen
      patient is allergic to these proteins. The results were confirmed by performing
      classical enzyme-linked immunosorbent assay of total and specific IgE Abs. The
      present IACE-UV/MALDI MS method required only 2 MUL of blood serum and allowed
      the performance of the total IgE quantification and CRD of the food allergy not
      only with the purified allergen molecules but also directly with the food
      extract. Such an approach opens the possibility for direct identification of
      allergens molecular mass and structure, discovery of unusual allergens, which
      could be useful for precise personalized allergy diagnostic, allergens epitope
      mapping, and cross-reactivity studies. 

PMID- 24915287
TI  - Characterization of an alkali- and halide-resistant laccase expressed in E. coli:
      CotA from Bacillus clausii.
AB  - The limitations of fungal laccases at higher pH and salt concentrations have
      intensified the search for new extremophilic bacterial laccases. We report the
      cloning, expression, and characterization of the bacterial cotA from Bacillus
      clausii, a supposed alkalophilic ortholog of cotA from B. subtilis. Both laccases
      were expressed in E. coli strain BL21(DE3) and characterized fully in parallel
      for strict benchmarking. We report activity on ABTS, SGZ, DMP, caffeic acid,
      promazine, phenyl hydrazine, tannic acid, and bilirubin at variable pH. Whereas
      ABTS, promazine, and phenyl hydrazine activities vs. pH were similar, the
      activity of B. clausii cotA was shifted upwards by ~0.5-2 pH units for the simple
      phenolic substrates DMP, SGZ, and caffeic acid. This shift is not due to
      substrate affinity (K(M)) but to pH dependence of catalytic turnover: The k(cat)
      of B. clausii cotA was 1 s-1 at pH 6 and 5 s-1 at pH 8 in contrast to 6 s-1 at pH
      6 and 2 s-1 at pH 8 for of B. subtilis cotA. Overall, k(cat)/K(M) was 10-fold
      higher for B. subtilis cotA at pH(opt). While both proteins were heat activated,
      activation increased with pH and was larger in cotA from B. clausii. NaCl
      inhibited activity at acidic pH, but not up to 500-700 mM NaCl in alkaline pH, a
      further advantage of the alkali regime in laccase applications. The B. clausii
      cotA had ~20 minutes half-life at 80 degrees C, less than the ~50 minutes at 80
      degrees C for cotA from B. subtilis. While cotA from B. subtilis had optimal
      stability at pH~8, the cotA from B. clausii displayed higher combined salt- and
      alkali-resistance. This resistance is possibly caused by two substitutions (S427Q
      and V110E) that could repel anions to reduce anion-copper interactions at the
      expense of catalytic proficiency, a trade-off of potential relevance to laccase
      optimization.

PMID- 24915290
TI  - Niche construction on environmental gradients: the formation of fitness valley
      and stratified genotypic distributions.
AB  - The process of niche construction can alter the trajectory of natural selection
      through organism-environment feedback. As such, the mechanism and impact of niche
      construction can be better investigated along environmental gradients. Here we
      investigate how the process of niche construction affects the distribution of
      genotypes and fitness landscape along an environmental gradient under three
      selection regimes, namely heterozygote superiority, genetic loci which dictates
      niche construction ability being either selectively neutral or non-neutral. Using
      a spatially explicit cellular automaton, we show that niche construction can
      stratify genetic diversity by forming band-like distributions consisting of
      different genotypic compositions and promote reproduction isolation by forming a
      divide with reduced average fitness along the gradients, termed a fitness valley.
      The band structure and the presence of a fitness valley depend on heterogeneous
      environments, resource-dependent fitness and the selection acting on the gene
      loci affecting the niche-constructing ability. Our work adds to the growing body
      of evidence on criticizing species distribution models which assume that the
      environment alone can determine species distributions. Based on the results, we
      argue that conservation planning should target preserving or restoring
      environmental gradients. 

PMID- 24915291
TI  - Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors
      of Bruton's tyrosine kinase with in vivo antitumor activity.
AB  - Bruton's tyrosine kinase (Btk) is an attractive drug target for treating several
      B-cell lineage cancers. Ibrutinib is a first-in-class covalent irreversible Btk
      inhibitor and has demonstrated impressive effects in multiple clinical trials.
      Herein, we present a series of novel 2,5-diaminopyrimidine covalent irreversible
      inhibitors of Btk. Compared with ibrutinib, these inhibitors exhibited a
      different selectivity profile for the analyzed kinases as well as a dual-action
      mode of inhibition of both Btk activation and catalytic activity, which
      counteracts a negative regulation loop for Btk. Two compounds from this series,
      31 and 38, showed potent antiproliferative activities toward multiple B-cell
      lymphoma cell lines, including germinal center B-cell-like diffuse large B cell
      lymphoma (GCB-DLBCL) cells. In addition, compound 31 significantly prevented
      tumor growth in a mouse xenograft model. 

PMID- 24915292
TI  - Acute pulmonary embolism due to hydatid cysts.

PMID- 24915293
TI  - Daily marital interaction quality and carotid artery intima-medial thickness in
      healthy middle-aged adults.
AB  - OBJECTIVE: To examine the association between marital interaction quality during
      daily life and subclinical cardiovascular disease (CVD). Studies have shown that
      marital status and quality of marriage are associated with cardiovascular health.
      However, little is known about the role of marital interaction quality during
      daily life in contributing to these effects. METHODS: The sample consisted of 281
      healthy, employed middle-aged adults who were married or living with a partner in
      a marital-like relationship (mean age = 42.0 years, 88% white, 52% men). Marital
      interaction quality was assessed using hourly real-time ecological momentary
      assessments for 4 days, with participants rating their current or recent partner
      interactions on positive and negative characteristics (e.g., agreeableness and
      conflict). Carotid artery intima-medial thickness (IMT) was assessed using
      ultrasound imaging. RESULTS: Adjusting for demographics, positive marital
      interaction was inversely associated with IMT (b = -0.02, F(1,275) = 9.18, p =
      .002), and negative marital interaction was positively associated with IMT (b =
      0.02 F(1,275) = 10.29, p = .001). These associations were not accounted for by
      behavioral and biological CVD risk factors and were consistent across age, sex,
      race, and education. The associations were also independent of marital
      interaction frequency, nonmarital social interaction quality, and personality
      factors. Global reports of marital quality, in contrast, were not associated with
      IMT. CONCLUSIONS: Marital quality as measured during real-time interactions
      between partners was associated with subclinical CVD in healthy middle-aged
      adults. This study supports the use of real-time social interaction assessment
      for characterizing links between social relationships and cardiovascular health.

PMID- 24915295
TI  - Brain networks underlying navigation in the Cincinnati water maze with external
      and internal cues.
AB  - The present study investigated the behavioural performance and the contributions
      of different brain regions on a spatial task performed by Wistar rats in the
      Cincinnati water maze (CWM) in two conditions: one where both distal and proximal
      visual cues were available (CWM-light group, n=7) and another where visual cues
      were eliminated by testing in complete darkness (CWM-dark group, n=7). There were
      differences in the behavioural performance. Energetic brain metabolism revealed
      significant differences in the infralimbic, orbitofrontal cortex and anterodorsal
      striatum. At the same time different brain networks were found. The CWM-light
      group showed a relationship between the orbitofrontal cortex and medial septum,
      whereas the CWM-dark group revealed three different networks involving the
      prefrontal cortex, ventral striatum, hippocampus and amygdala nuclei. The study
      shows that brain activation differs in these two conditions. 

PMID- 24915294
TI  - Evaluation of the association between placental corticotrophin-releasing hormone
      and postpartum depressive symptoms.
AB  - OBJECTIVE: Postpartum depression (PPD) represents a significant threat to
      maternal-child health. Although PPD is common, with an estimated prevalence of
      10% to 15%, critical questions concerning its etiology remain unanswered.
      Existing studies seem to provide conflicting evidence regarding the relation
      between placental corticotrophin-releasing hormone (pCRH) and the development of
      PPD. The purpose of the present investigation was to determine whether maternal
      prepartum hypothalamic-pituitary-adrenal and placental dysregulation, in
      particular elevated midgestational pCRH, represent markers of risk for the
      development of PPD symptoms. METHODS: One hundred seventy adult women with
      singleton, term pregnancies were recruited during the first trimester and
      participated in study visits at 15, 19, 25, 31, and 36+ weeks' gestation and at 3
      and 6 months postpartum. At each prenatal visit, blood samples were obtained and
      assayed to determine maternal cortisol, adrenocorticotropic hormone, and pCRH
      concentrations. Depressive symptoms were assessed at all visits. RESULTS:
      Depressive symptoms at 3 months postpartum were associated with elevated
      midgestational pCRH (partial r = 0.26; p < .01) and also accelerated trajectories
      of pCRH (B values ranged from 6.9 to 8.3, p < .05). Placental CRH was not
      predictive of PPD symptoms at 6 months postpartum. Furthermore, prepartum
      cortisol and corticotrophin profiles were not associated with PPD symptoms.
      CONCLUSIONS: The current prospective study provides results that reconcile both
      the positive and negative findings in the existing literature and identifies
      elevated pCRH as a marker of risk for the development of PPD symptoms.

PMID- 24915297
TI  - The role of the FM component in shaping the number of impulses and response
      latency of inferior collicular neurons of Hipposideros armiger elicited by CF-FM
      sounds.
AB  - Previous studies show that when stimulated with constant frequency-frequency
      modulated (CF-FM) sounds, the inferior collicular neurons of the leaf-nosed bat,
      Hipposideros armiger, either discharge impulses only to the CF component (single
      on, SO neurons) or to both CF and FM components (double-on, DO neurons). In this
      study, we specifically determine the role of the FM component in shaping the
      number of impulses and response latency of these two types of neurons in response
      to CF-FM sounds. Adding the FM component to the CF sounds significantly decreases
      the number of impulses of both SO and DO neurons but shortens the response
      latency of DO neurons in response to the CF component of the CF-FM sounds. The
      possible neural mechanisms underlying these seemingly paradoxical observations
      are briefly discussed based on our preliminary intracellular recording studies.
      Biological relevance of these findings in relation to different phases of bats'
      hunting is also discussed. 

PMID- 24915296
TI  - Orexin-1 receptor mediates the increased food and water intake induced by
      intracerebroventricular injection of the stable somatostatin pan-agonist, ODT8
      SST in rats.
AB  - Intracerebroventricular (icv) injection of the stable somatostatin pan-agonist,
      ODT8-SST induces a somatostatin 2 receptor (sst2) mediated robust feeding
      response that involves neuropeptide Y and opioid systems in rats. We investigated
      whether the orexigenic system driven by orexin also plays a role. Food and water
      intake after icv injection was measured concomitantly in non-fasted and non-water
      deprived rats during the light phase. In vehicle treated rats (100% DMSO, icv),
      ODT8-SST (1MUg/rat, icv) significantly increased the 2-h food and water intake
      compared to icv vehicle plus saline (5.1+/-1.0g vs. 1.2+/-0.4g and 11.3+/-1.9mL
      vs. 2.5+/-1.2mL, respectively). The orexin-1 receptor antagonist, SB-334867
      (16MUg/rat, icv) completely inhibited the 2-h food and water intake induced by
      icv ODT8-SST. In contrast, the icv pretreatment with the selective somatostatin
      sst2 antagonist, S-406-028, established to block the orexigenic effect of icv
      ODT8-SST, did not modify the increased food and water intake induced by icv
      orexin-A (10.7MUg/rat). These data indicate that orexin-1 receptor signaling
      system is part of the brain neurocircuitry contributing to the orexigenic and
      dipsogenic responses induced by icv ODT8-SST and that orexin-A stimulates food
      intake independently from brain sst2 activation. 

PMID- 24915300
TI  - The state of interprofessional collaboration in Northern Italy: a mixed methods
      study.
AB  - Health care systems are facing continual reorganizations in response to
      scientific and technological innovations as well as financial constraints.
      Simultaneously the rising prevalence of chronic diseases call for a kind of
      health care organization in which interprofessional collaboration (IPC) functions
      on a high level. This article describes a research project that aims to generate
      an empirical account of the current state of IPC in the South Tyrolean Health
      Trust, located in a bilingual region in northern Italy. The study will employ a
      sequential mixed methods' design. A survey will be followed by individual and
      focus group interviews. An innovative aspect of the study is that it will include
      participants from six different health professions (dieticians, nurses,
      occupational therapists, physicians, physiotherapists, and speech therapists).
      Qualitative data analysis will draw on the negotiated order/structural ordering
      approach and on the social world/arena perspective. The results are expected to
      generate specific recommendations to improve IPC in the South Tyrolean Health
      Trust and inform further research.

PMID- 24915299
TI  - Oxytocin is an age-specific circulating hormone that is necessary for muscle
      maintenance and regeneration.
AB  - The regenerative capacity of skeletal muscle declines with age. Previous studies
      suggest that this process can be reversed by exposure to young circulation;
      however, systemic age-specific factors responsible for this phenomenon are
      largely unknown. Here we report that oxytocin--a hormone best known for its role
      in lactation, parturition and social behaviours--is required for proper muscle
      tissue regeneration and homeostasis, and that plasma levels of oxytocin decline
      with age. Inhibition of oxytocin signalling in young animals reduces muscle
      regeneration, whereas systemic administration of oxytocin rapidly improves muscle
      regeneration by enhancing aged muscle stem cell activation/proliferation through
      activation of the MAPK/ERK signalling pathway. We further show that the genetic
      lack of oxytocin does not cause a developmental defect in muscle but instead
      leads to premature sarcopenia. Considering that oxytocin is an FDA-approved drug,
      this work reveals a potential novel and safe way to combat or prevent skeletal
      muscle ageing.

PMID- 24915302
TI  - Comparative analysis of pathology and boronophenylalanine uptake in experimental
      orthotopic and heterotopic amelanotic melanoma.
AB  - Pathobiologic characteristics of cerebral and cutaneous melanoma may cause an
      increase in mortality resulting from brain metastases in advanced melanoma
      patients, in addition to anatomic lesions and biological effects caused by the
      tumor location. We established intracranial and subcutaneous melanoma models
      using cultured malignant cells derived from amelanotic melanoma. The median
      survival times in a mouse model with intracranial tumors was 20 days, but a mouse
      model with subcutaneous tumors did not show cachexia until they were killed 28
      days after inoculation with tumor cells. Histopathological analysis showed that a
      high karyokinesis phase and nuclear pleomorphism appeared in the intracranial
      model compared with the subcutaneous tumor model mice. The tumor boron
      concentration at 2.5 h after boronophenylalanine administration was 15.21+/-3.88
      MUg/g in an intracranial melanoma xenograft and 19.85+/-3.63 MUg/g in a
      subcutaneous melanoma xenograft. Intracranial melanoma showed more malignancy and
      shorter survival time than did subcutaneous melanoma when the same number of
      tumor cells were injected, and subcutaneous and intracranial amelanotic malignant
      melanoma tumors are both fitted for boron neutron capture therapy. 

PMID- 24915301
TI  - Inhibition of chemokine (C-C motif) receptor 7 sialylation suppresses CCL19
      stimulated proliferation, invasion and anti-anoikis.
AB  - Chemokine (C-C motif) receptor 7 (CCR7) is involved in lymph-node homing of naive
      and regulatory T cells and lymphatic metastasis of cancer cells. Sialic acids
      comprise a group of monosaccharide units that are added to the terminal position
      of the oligosaccharide chain of glycoproteins by sialyation. Recent studies
      suggest that aberrant sialylation of receptor proteins contributes to
      proliferation, motility, and drug resistance of cancer cells. In this study, we
      addressed whether CCR7 is a sialylated receptor protein and tried to elucidate
      the effect of sialylation in the regulation of signal transduction and biological
      function of CCR7. Our results demonstrated that alpha-2, 3-sialyltransferase
      which catalyze sialylation reaction in vivo was overexpressed in breast tumor
      tissues and cell lines. Lectin blot analysis clearly demonstrated that CCR7
      receptor was sialyated in breast cancer cells. Chemokine (C-C motif) ligand 19
      (CCL19), the cognate ligand for CCR7, induced the activation of extracellular
      signal-regulated kinase (ERK) and AKT signaling and increased the expression of
      cell cycle regulatory proteins and proliferation of breast cancer cells. When
      cells were pre-treated with a sialyltransferase inhibitor AL10 or sialidase,
      CCL19-induced cell growth was significantly suppressed. CCL19 also increased
      invasion and prevented anoikis by up-regulating pro-survival proteins Bcl-2 and
      Bcl-xL. Inhibition of sialylation by AL10 totally abolished these effects.
      Finally, we showed that AL10 inhibited tumorigenicity of breast cancer in
      experimental animals. Taken together, we demonstrate for the first time that CCR7
      receptor is a sialylated protein and sialylation is important for the paracrine
      stimulation by its endogenous ligand CCL19. In addition, inhibition of aberrant
      sialylation of CCR7 suppresses proliferation and invasion and triggers anoikis in
      breast cancer cells. Targeting of sialylation enzymes may be a novel strategy for
      breast cancer treatment. 

PMID- 24915298
TI  - The autophagic roles of Rab small GTPases and their upstream regulators: a
      review.
AB  - Macroautophagy is an evolutionarily conserved degradative process of eukaryotic
      cells. Double-membrane vesicles called autophagosomes sequester portions of
      cytoplasm and undergo fusion with the endolysosomal pathway in order to degrade
      their content. There is growing evidence that members of the small GTPase RAB
      protein family-the well-known regulators of membrane trafficking and fusion
      events-play key roles in the regulation of the autophagic process. Despite
      numerous studies focusing on the functions of RAB proteins in autophagy, the
      importance of their upstream regulators in this process emerged only in the past
      few years. In this review, we summarize recent advances on the effects of RABs
      and their upstream modulators in the regulation of autophagy. Moreover, we
      discuss how impairment of these proteins alters the autophagic process leading to
      several generally known human diseases. 

PMID- 24915303
TI  - Molecular encoder-decoder based on an assembly of graphene oxide with dye
      labelled DNA.
AB  - A general strategy was developed to fabricate 2-to-1, 4-to-2 and 8-to-3 molecular
      encoders and a 1-to-2 decoder by assembling graphene oxide with various dye
      labeled DNAs. 

PMID- 24915304
TI  - Synthesis of triple-bond-containing 1-hydroxy-1,1-bisphosphonic acid derivatives
      to be used as precursors in "click" chemistry: two examples.
AB  - The synthesis of novel (omega-alkynyl-1-hydroxy-1,1-diyl)bisphosphonic acid
      tetramethyl esters (1a-c), their P,P'-dimethyl esters (2a-c), and two trimethyl
      ester derivatives (3a and 3b) is reported. The prepared compounds can be attached
      to many kinds of molecules containing azide (-N3) functionalities using a "click"
      chemistry approach. As an example, bisphosphonate trimethyl ester 3a and P,P'
      dimethyl ester 2b were attached to triethylene glycol to form triethylene glycol
      bisphosphonate conjugates 4 and 5 as model compounds for further studies in, for
      example, nanoparticle targeting. 

PMID- 24915305
TI  - Understanding the effect of fluorocarbons in aqueous supramolecular
      polymerization: ultrastrong noncovalent binding and cooperativity.
AB  - Achieving supramolecular polymerization based on strong yet reversible bonds
      represents a significant challenge. A solution may be offered by perfluoroalkyl
      groups, which have remarkable hydrophobicity. We tested the idea that a
      perfluorooctyl chain attached to a perylene diimide amphiphile can dramatically
      enhance the strength of supramolecular bonding in aqueous environments.
      Supramolecular structures and polymerization thermodynamics of this fluorinated
      compound (1-F) were studied in comparison to its non-fluorinated analogue (1-H).
      Depending on the amount of organic cosolvent, 1-F undergoes cooperative or
      isodesmic aggregation. The switching between two polymerization mechanisms
      results from a change in polymer structure, as observed by cryogenic electron
      microscopy. 1-F showed exceptionally strong noncovalent binding, with the largest
      directly measured association constant of 1.7 * 10(9) M(-1) in 75:25 water/THF
      mixture (v/v). In pure water, the association constant of 1-F is estimated to be
      at least in the order of 10(15) M(-1) (based on extrapolation), 3 orders of
      magnitude larger than that of 1-H. The difference in aggregation strength between
      1-F and 1-H can be explained solely on the basis of the larger surface area of
      the fluorocarbon group, rather than a unique nature of fluorocarbon
      hydrophobicity. However, differences in aggregation mechanism and cooperativity
      exhibited by 1-F appear to result from specific fluorocarbon conformational
      rigidity. 

PMID- 24915307
TI  - Near-infrared Spectroscopy in the Brewing Industry.
AB  - This article offers an exhaustive description of the use of Near-Infrared (NIR)
      Spectroscopy in the brewing industry. This technique is widely used for quality
      control testing of raw materials, intermediates, and finished products, as well
      as process monitoring during malting and brewing. In particular, most of the
      reviewed works focus on the assessment of barley properties, aimed at quickly
      selecting the best barley varieties in order to produce a high-quality malt
      leading to high-quality beer. Various works concerning the use of NIR in the
      evaluation of raw materials, such as barley, malt, hop, and yeast, are also
      summarized here. The implementation of NIR sensors for the control of malting and
      brewing processes is also highlighted, as well as the use of NIR for quality
      assessment of the final product. 

PMID- 24915308
TI  - Quality-related enzymes in plant-based products: effects of novel food-processing
      technologies part 3: ultrasonic processing.
AB  - High-power ultrasound is a versatile technology which can potentially be used in
      many food processing applications including food preservation. This is part 2 of
      a series of review articles dealing with the effectiveness of nonthermal food
      processing technologies in food preservation focusing on their effect on enzymes.
      Typically, ultrasound treatment alone does not efficiently cause microbial or
      enzyme inactivation sufficient for food preservation. However, combined with mild
      heat with or without elevated pressure (P <= 500 kPa), ultrasound can effectively
      inactivate enzymes and microorganisms. Synergistic effects between ultrasound and
      mild heat have been reported for the inactivation of both enzymes and
      microorganisms. The application of ultrasound has been shown to enhance the rate
      of inactivation of quality degrading enzymes including pectin methylesterase
      (PME), polygalacturonase (PG), peroxidase (POD), polyphenol oxidase (PPO), and
      lipoxygenase (LOX) at mild temperature by up to 400 times. Moreover, ultrasound
      enables the inactivation of relatively heat-resistant enzymes such as tomato PG1
      and thermostable orange PME at mild temperature conditions. The extent to which
      ultrasound enhances the inactivation rate depends on the type of enzyme, the
      medium in which the enzyme is suspended, and the processing condition including
      frequency, ultrasonic intensity, temperature, and pressure. The physical and
      chemical effects of cavitation are considered to be responsible for the
      ultrasound-induced inactivation of enzymes, although the dominant mechanism
      depends on the structure of the enzyme.

PMID- 24915306
TI  - Association between melanocytic nevi and risk of breast diseases: The French E3N
      prospective cohort.
AB  - BACKGROUND: While melanocytic nevi have been associated with genetic factors and
      childhood sun exposure, several observations also suggest a potential hormonal
      influence on nevi. To test the hypothesis that nevi are associated with breast
      tumor risk, we explored the relationships between number of nevi and benign and
      malignant breast disease risk. METHODS AND FINDINGS: We prospectively analyzed
      data from E3N, a cohort of French women aged 40-65 y at inclusion in 1990. Number
      of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95%
      confidence intervals (CIs) were calculated using Cox proportional hazards
      regression models. Associations of number of nevi with personal history of benign
      breast disease (BBD) and family history of breast cancer were estimated using
      logistic regression. Over the period 15 June 1990-15 June 2008, 5,956 incident
      breast cancer cases (including 5,245 invasive tumors) were ascertained among
      89,902 women. In models adjusted for age, education, and known breast cancer risk
      factors, women with "very many" nevi had a significantly higher breast cancer
      risk (HR = 1.13, 95% CI = 1.01-1.27 versus "none"; ptrend = 0.04), although
      significance was lost after adjustment for personal history of BBD or family
      history of breast cancer. The 10-y absolute risk of invasive breast cancer
      increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674
      4,649) per 100,000 women with "very many" nevi. The association was restricted to
      premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR =
      1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast
      cancer type or hormone receptor status. In addition, we observed significantly
      positive dose-response relationships between number of nevi and history of biopsy
      confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in
      first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our
      study include self-report of number of nevi using a qualitative scale, and self
      reported history of biopsied BBD. CONCLUSIONS: Our findings suggest associations
      between number of nevi and the risk of premenopausal breast cancer, BBD, and
      family history of breast cancer. More research is warranted to elucidate these
      relationships and to understand their underlying mechanisms.

PMID- 24915309
TI  - Xylitol: a review on bioproduction, application, health benefits, and related
      safety issues.
AB  - Xylitol is a pentahydroxy sugar-alcohol which exists in a very low quantity in
      fruits and vegetables (plums, strawberries, cauliflower, and pumpkin). On
      commercial scale, xylitol can be produced by chemical and biotechnological
      processes. Chemical production is costly and extensive in purification steps.
      However, biotechnological method utilizes agricultural and forestry wastes which
      offer the possibilities of economic production of xylitol by reducing required
      energy. The precursor xylose is produced from agricultural biomass by chemical
      and enzymatic hydrolysis and can be converted to xylitol primarily by yeast
      strain. Hydrolysis under acidic condition is the more commonly used practice
      influenced by various process parameters. Various fermentation process inhibitors
      are produced during chemical hydrolysis that reduce xylitol production, a
      detoxification step is, therefore, necessary. Biotechnological xylitol production
      is an integral process of microbial species belonging to Candida genus which is
      influenced by various process parameters such as pH, temperature, time, nitrogen
      source, and yeast extract level. Xylitol has application and potential for food
      and pharmaceutical industries. It is a functional sweetener as it has prebiotic
      effects which can reduce blood glucose, triglyceride, and cholesterol level. This
      review describes recent research developments related to bioproduction of xylitol
      from agricultural wastes, application, health, and safety issues. 

PMID- 24915310
TI  - Structural and functional analysis of various globulin proteins from soy seed.
AB  - Storage proteins of soybean mostly consist of globulins, which are classified
      according to their sedimentation coefficient. Among 4 major types: 2S, 7S, 11S,
      and 15S of globulins, 7S and 11S constitute major fraction. The 11S fraction
      consists only of glycinin and 7S fraction majorly consists of beta-conglycinin,
      small amounts of gamma-conglycinin and basic 7S globulin (Bg7S). Glycinin exist
      as a hexamer while beta-conglycinin as a trimer and Bg7S as a tetramer. Glycinin
      subunits are coded by 5 genes of a family, whereas about 15 genes are present for
      beta-conglycinin subunits. Bg7S gene is present in four copies in soybean genome.
      Synthesis of all proteins takes place as a single polypeptide chain, which is
      cleaved after folding to yield different chains or subunits. Glycinin and beta
      Conglycinin are made for storage purpose. However, Bg7S has potential xylanase
      inhibition activity and protein kinase activity. Primary structure of Bg7S
      reveals 12 conserved cysteine residues involved in forming 6 disulfide bonds,
      which provides appreciable stability to protein. Secondary structure is
      predominately rich in beta-sheets with few alpha helices. Bg7S shares structural
      similarity with various aspartic-proteases. In this review, our aim is to discuss
      sequence, structure, and function of various globulins present in Glycine max. 

PMID- 24915311
TI  - Slowly digestible starch--a review.
AB  - The link between carbohydrate intake and health is becoming increasingly
      important for consumers, particularly in the areas of glycemic index (GI) and
      extended energy-releasing starches. From a physiological point of view, slowly
      digestible starch (SDS) delivers a slow and sustained release of blood glucose
      along with the benefits resulting from low glycemic and insulinemic response. SDS
      has been implicated in several health problems, including diabetes, obesity, and
      cardiovascular diseases (metabolic syndromes). It may also have commercial
      potential as a novel functional ingredient in a variety of fields, such as
      nutrition, medicine, and agriculture. The present review assesses this form of
      digestion by analyzing methods to prepare and evaluate SDS, and factors affecting
      its transformation, its health benefits, and its applications. 

PMID- 24915312
TI  - A comprehensive survey of fruit grading systems for tropical fruits of
      Maharashtra.
AB  - It is said that the backbone of Indian economy is agriculture. The contribution
      of the agriculture sector to the national GDP (Gross Domestic Products) was 14.6%
      in the year 2010. To attain a growth rate equivalent to that of industry (viz.,
      about 9%), it is highly mandatory for Indian agriculture to modernize and use
      automation at various stages of cultivation and post-harvesting techniques. The
      use of computers in assessing the quality of fruits is one of the major
      activities in post-harvesting technology. As of now, this assessment is majorly
      done manually, except for a few fruits. Currently, the fruit quality assessment
      by machine vision in India is still at research level. Major research has been
      carried out in countries like China, Malaysia, UK, and Netherlands. To suit the
      Indian market and psychology of Indian farmers, it is necessary to develop
      indigenous technology. This paper is the first step toward evaluating the
      research carried out by the research community all over world for tropical
      fruits. For the purpose of survey, we have concentrated on the tropical fruits of
      the state of Maharashtra, while keeping in focus of the review image processing
      algorithms. 

PMID- 24915313
TI  - Effect of processing on mycotoxin content in grains.
AB  - Mycotoxins that commonly occur in cereal grains and other products can
      contaminate finished processed foods on account of their high toxicity. The
      mycotoxins that are commonly associated with food grains include aflatoxins,
      ochratoxin A, fumonisins, deoxynivalenol, and zearalenone. Various food
      processing operations include sorting, trimming, cleaning, cooking, baking,
      frying, roasting, flaking, and extrusion that have variable effects on
      mycotoxins. The nature of the processing operation viz. physical, chemical, or
      thermal plays an important role in this; usually, the processes that utilize the
      higher temperatures have greater effects on mycotoxin dissipation. In general,
      the processes are known to reduce mycotoxin concentrations significantly, but do
      not eliminate them completely. However, roasting and extrusion processing result
      in lowest mycotoxin concentrations, since these involve higher temperatures. It
      is observed that very high temperatures are needed to bring about high reduction
      in mycotoxin concentrations, approaching acceptable background levels. The
      treatment with chemicals like ammonia, bicarbonate, citric acid, or sodium
      bisulfite is also effective in resulting in significant decline in mycotoxin
      concentrations. 

PMID- 24915314
TI  - Fruit-based Natural Antioxidants in Meat and Meat Products: A Review.
AB  - Due to the potential toxic effects of synthetic antioxidants, natural antioxidant
      sources especially fruits are being preferred now-a-days for use in different
      meat products. The majority of the antioxidant capacity of a fruit is especially
      because of numerous phenolic compounds. Many of the phytochemicals present in
      fruits may help protect cells against the oxidative damage caused by free
      radicals, thereby reducing the risk of degenerative diseases such as
      cardiovascular diseases, various types of cancers, and neurological diseases.
      Various parts of the fruit including their byproducts like skin and seeds have
      been used in meat products. Plum has been used as plum puree, prunes (dried
      plum), and plum extracts. Grape skin, seed, peel extracts, and grape pomace;
      berries as cakes and powder extracts; pomegranate rind powder and its juice; and
      most of the citrus fruits have proved beneficial sources of antioxidants. All
      these natural sources have effectively reduced the thiobarbituric acid-reactive
      substances (TBARS) values and free radical frequency. Thus, lipid oxidation is
      prevented and shelf life is greatly enhanced by incorporating various kinds of
      fruits and their byproducts in meat and meat products. There is a great scope for
      the use of fruits as natural sources of antioxidants in meat industry. The review
      is intended to provide an overview of the fruit-based natural antioxidants in
      meat and meat products. 

PMID- 24915315
TI  - Nutrient Recommendations for Growing-up Milk: A Report of an Expert Panel.
AB  - Utilization of expert recommendations in the development of food and beverage
      nutritional profiles represents an opportunity to merge science and food
      manufacturing to deliver nutritionally optimized products into the marketplace.
      This report details expert panel guidelines for the design of a nutritional
      product for children one to six years of age. This interaction demonstrates the
      essential synergy between academia and food manufacturers in translating nutrient
      recommendations to food for their delivery to a population. Important factors for
      such translation are the identification of applicable nutrient recommendations
      and selection of an appropriate delivery matrix. This report demonstrates the
      translation of expert nutritional recommendations to a milk-based product for
      children--one to six years of age.

PMID- 24915316
TI  - Bacterial production of conjugated linoleic and linolenic Acid in foods: a
      technological challenge.
AB  - Conjugated linoleic acid (CLA) and conjugated linolenic acid (CLNA) isomers are
      present in foods derived from ruminants as a result of the respective linoleic
      acid (LA) and alpha-linolenic acid (LNA) metabolism by ruminal microorganisms and
      in animals' tissues. CLA and CLNA have isomer-specific, health-promoting
      properties, including anticarcinogenic, antiatherogenic, anti-inflammatory, and
      antidiabetic activity, as well as the ability to reduce body fat. Besides ruminal
      microorganisms, such as Butyrivibrio fibrisolvens, many food-grade bacteria, such
      as bifidobacteria, lactic acid bacteria (LAB), and propionibacteria, are able to
      convert LA and LNA to CLA and CLNA, respectively. Linoleate isomerase activity,
      responsible for this conversion, is strain-dependent and probably related to the
      ability of the producer strain to tolerate the toxic effects of LA and LNA. Since
      natural concentrations of CLA and CLNA in ruminal food products are relatively
      low to exert their health benefits, food-grade bacteria with linoleate isomerase
      activity could be used as starter or adjunct cultures to develop functional
      fermented dairy and meat products with increased levels of CLA and CLNA or
      included in fermented products as probiotic cultures. However, results obtained
      so far are below expectations due to technological bottlenecks. More research is
      needed to assess if bacterial production kinetics can be increased and can match
      food processing requirements. 

PMID- 24915317
TI  - Enhancement of attributes of cereals by germination and fermentation: a review.
AB  - The nutritional quality of cereals and the sensorial properties of their products
      are sometimes inferior as compared to other sources of food which is due to the
      lower protein content and starch availability, the presence of determined
      antinutrients (phytic acid, tannins, and polyphenols) and the coarse nature of
      the grains. To ameliorate the nutritional qualities of cereals, they are
      processed in a number of ways. This review summarizes the enhancement in the
      nutritional value as well as the functional characteristics of cereals due to
      germination and fermentation treatment. The protein concentration increases and
      the amino acid profile is balanced by germination and fermentation. The
      antinutritional factors are reduced increasing the mineral availability from the
      cereals. Germination enhances the quality of nutrients and bioactive compounds of
      cereals thereby increasing the content in proteins, amino acids, sugars, and
      vitamins. The functional properties of cereals is enhanced due to generation of
      biofunctional substances, increase in protein solubility, in vitro protein
      digestibility and lowering of glycemic index. 

PMID- 24915318
TI  - Healthy virgin olive oil: a matter of bitterness.
AB  - Virgin olive oil (VOO) is the pillar fat of Mediterranean diet. It is made from
      olive fruits and obtained by squeezing olives without any solvent extraction.
      Respect to the seed oils, an unique polar polyphenol-rich fraction gives VOO a
      bitter and pungent taste. The recent substantiation by European Food Safety
      Authority (EFSA) of a health claim for VOO polyphenols may represent an efficient
      stimulus to get the maximum health benefit from one of the most valuable
      traditional product of Mediterranean countries educating consumers to the
      relationship between the VOO bitterness and its health effect. Agronomical
      practices and new processing technology to avoid phenolic oxidation and
      hydrolysis and to enhance the aromatic components of the VOO have been developed
      and they can be used to modulate taste and flavor to diversify the products on
      the market. VOOs having high concentration of phenol compounds are bitter and
      pungent therefore many people do not consume them, thus loosing the health
      benefits related to their intake. In this paper, the chemist's and nutritionist's
      point of view has been considered to address possible strategies to overcome the
      existing gap between the quality perceived by consumer and that established by
      expert tasters. Educational campaigns emphasizing the bitter-health link for
      olive oils should be developed.

PMID- 24915319
TI  - A review on the structure-function relationship aspect of polysaccharides from
      tea materials.
AB  - Tea (Camellia sinensis) has a long history of medicinal use in the world. The
      chemical components of tea mainly consist of polyphenols (TPP), proteins,
      polysaccharides (TPS), chlorophyll, alkaloids, and so on. Great advances have
      been made in chemical and bioactive studies of catechins and TPP from tea in
      recent decades. However, the TPS from tea materials have received much less
      consideration than that of TPP. The number of relevant publications on the TPS
      from tea leaves and flowers has increased rapidly in recent years. This mini
      review summarizes the structure-function relationship of TPS from tea leaves and
      flowers. The application of purified TPS from tea material as functional or
      nutritional foods was still little. It will help to develop the function foods
      with tea TPS and better understand the structure-bioactivity relationship of tea
      TPS. 

PMID- 24915320
TI  - Meat analog: a review.
AB  - The health-conscious consumers are in search of nutritious and convenient food
      item which can be best suited in their busy life. The vegetarianism is the key
      for the search of such food which resembles the meat in respect of nutrition and
      sensory characters, but not of animal origin and contains vegetable or its
      modified form, this is the point when meat analog evolved out and gets shape. The
      consumers gets full satisfaction by consumption of meat analog due to its typical
      meaty texture, appearance and the flavor which are being imparted during the
      skilled production of meat analog. The supplement of protein in vegetarian diet
      through meat alike food can be fulfilled by incorporating protein-rich vegetative
      food grade materials in meat analog and by adopting proper technological process
      which can promote the proper fabrication of meat analog with acceptable meat like
      texture, appearance, flavor, etc. The easily available vegetables, cereals, and
      pulses in India have great advantages and prospects to be used in food products
      and it can improve the nutritional and functional characters of the food items.
      The various form and functional characters of food items are available world over
      and attracts the meat technologists and the food processors to bring some
      innovativeness in meat analog and its presentation and marketability so that the
      acceptability of meat analog can be overgrown by the consumers. 

PMID- 24915321
TI  - Determination of sex origin of meat and meat products on the DNA basis: a review.
AB  - Sex determination of domestic animal's meat is of potential value in meat
      authentication and quality control studies. Methods aiming at determining the sex
      origin of meat may be based either on the analysis of hormone or on the analysis
      of nucleic acids. At the present time, sex determination of meat and meat
      products based on hormone analysis employ gas chromatography-mass spectrometry
      (GC-MS), high-performance liquid chromatography-mass spectrometry/mass
      spectrometry (HPLC-MS/MS), and enzyme-linked immunosorbent assay (ELISA). Most of
      the hormone-based methods proved to be highly specific and sensitive but were not
      performed on a regular basis for meat sexing due to the technical limitations or
      the expensive equipments required. On the other hand, the most common methodology
      to determine the sex of meat is unquestionably traditional polymerase chain
      reaction (PCR) that involves gel electrophoresis of DNA amplicons. This review is
      intended to provide an overview of the DNA-based methods for sex determination of
      meat and meat products. 

PMID- 24915322
TI  - Molecular methods for microbiological quality control of meat and meat products:
      a review.
AB  - Achieving food safety is a global health goal and the food-borne diseases take a
      major check on global health. Therefore, detection of microbial pathogens in food
      is the solution to the prevention and recognition of problems related to health
      and safety. Conventional and standard bacterial detection methods such as culture
      and colony counting methods and immunology-based methods may take up to several
      hours or even a few days to yield a result. Obviously, this is inadequate, and
      recently many researchers are focusing towards the progress of rapid diagnostic
      methods. The advent of molecular techniques has led to the development of a
      diverse array of assay for quality control of meat and meat products. Rapid
      analysis using DNA hybridization and amplification techniques offer more
      sensitivity and specificity to get results than culture based methods as well as
      dramatic reduction in the time to get results. Many methods have also achieved
      the high level automation, facilitating their application as routine sample
      screening assays. This review is intended to provide an overview of the molecular
      methods for microbiological quality control of meat and meat products. 

PMID- 24915323
TI  - Essential oils as natural food antimicrobial agents: a review.
AB  - Food-borne illnesses pose a real scourge in the present scenario as the
      consumerism of packaged food has increased to a great extend. Pathogens entering
      the packaged foods may survive longer, which needs a check. Antimicrobial agents
      either alone or in combination are added to the food or packaging materials for
      this purpose. Exploiting the antimicrobial property, essential oils are
      considered as a "natural" remedy to this problem other than its flavoring
      property instead of using synthetic agents. The essential oils are well known for
      its antibacterial, antiviral, antimycotic, antiparasitic, and antioxidant
      properties due to the presence of phenolic functional group. Gram-positive
      organisms are found more susceptible to the action of the essential oils.
      Essential oils improve the shelf-life of packaged products, control the microbial
      growth, and unriddle the consumer concerns regarding the use of chemical
      preservatives. This review is intended to provide an overview of the essential
      oils and their role as natural antimicrobial agents in the food industry. 

PMID- 24915324
TI  - Identification of species origin of meat and meat products on the DNA basis: a
      review.
AB  - The adulteration/substitution of meat has always been a concern for various
      reasons such as public health, religious factors, wholesomeness, and unhealthy
      competition in meat market. Consumer should be protected from these malicious
      practices of meat adulterations by quick, precise, and specific identification of
      meat animal species. Several analytical methodologies have been employed for meat
      speciation based on anatomical, histological, microscopic, organoleptic,
      chemical, electrophoretic, chromatographic, or immunological principles. However,
      by virtue of their inherent limitations, most of these techniques have been
      replaced by the recent DNA-based molecular techniques. In the last decades,
      several methods based on polymerase chain reaction have been proposed as useful
      means for identifying the species origin in meat and meat products, due to their
      high specificity and sensitivity, as well as rapid processing time and low cost.
      This review intends to provide an updated and extensive overview on the DNA-based
      methods for species identification in meat and meat products. 

PMID- 24915326
TI  - Shelf-life Reduction as an Emerging Problem in Cooked Hams Underlines the Need
      for Improved Preservation Strategies.
AB  - Cooked hams have gained an important position within the delicatessen market.
      Nowadays, consumers not only demand superior sensory properties but also request
      low levels of sodium and fat and the absence of conventional chemicals and
      preservatives used for the increase of the technological yield and shelf-life of
      the products. As a result, products that apply strict quality certificates or
      ''clean'' labels become increasingly important. However, such cooked hams suffer
      from a limited shelf-life. Besides some physicochemical effects, this is mainly
      due to microbial impact, despite the application of modified-atmosphere-packaging
      and chilling. Microbial spoilage is mostly due to the metabolic manifestation of
      lactic acid bacteria and Brochothrix thermosphacta, although Enterobacteriaceae
      and yeasts may occur too. Several preservation strategies have been developed to
      prolong the shelf-life of such vulnerable cooked meat products by targeting the
      microbial communities, with different rates of success. Whereas high-pressure
      treatments do not always pose a straightforward solution, a promising strategy
      relates to the use of bioprotective cultures containing lactic acid bacteria. The
      latter consist of strains that are deliberately added to the ham to outcompete
      undesirable microorganisms. Spoilage problems seem, however, to be specific for
      each product and processing line, underlining the importance of tailor-made
      solutions. 

PMID- 24915325
TI  - Tocopherols in Seafood and Aquaculture Products.
AB  - Fish products contain various nutritionally beneficial components, namely, omega3
      polyunsaturated fatty acids (omega3-PUFA), minerals, and vitamins. Particularly,
      tocopherols (alpha-, beta-, gamma-, and delta-tocopherol) can be provided by
      seafood and aquaculture products. Hence, this review shows the various aspects of
      tocopherols in seafood and aquaculture products. For tocopherol determination in
      these products, HPLC methods coupled with diode array detection in the UV area of
      the spectrum or fluorescence detection have been shown as sensitive and accurate.
      These newest methods have helped in understanding tocopherols fate upon ingestion
      by seafood organisms. Tocopherols pass through the intestinal mucosa mainly by
      the same passive diffusion mechanism as fats. After absorption, the transport
      mechanism is thought to consist of two loops. The first loop is dietary,
      including chylomicrons and fatty acids bound to carrier protein, transporting
      lipids mainly to the liver. The other is the transport from the liver to tissues
      and storage sites. Moreover, tocopherol levels in fish organisms correlate with
      diet levels, being adjusted in fish body depending on diet concentration. For
      farmed fish species, insufficient levels of tocopherols in the diet can lead to
      poor growth performance or to nutritional disease. The tocopherol quantity needed
      as a feed supplement depends on various factors, such as the vitamer mixture, the
      lipid level and source, the method of diet preparation, and the feed storage
      conditions. Other ingredients in diet may be of great importance, it has been
      proposed that alpha-tocopherol may behave as a prooxidant synergist at higher
      concentrations when prooxidants such as transition metals are present. However,
      the antioxidant action of tocopherols outweighs this prooxidant effect, provided
      that adequate conditions are used. In fact, muscle-based foods containing higher
      levels of tocopherol show, for instance, higher lipid stability. Besides,
      tocopherols are important not only from the nutritional point of view but also
      from the physiological one, since they are involved in many metabolic processes
      in the human organism. Moreover, synergistic interactions with selenium and
      ascorbic acid have been reported. It deserves attention that there is evidence
      tocopherols taken with food can prevent heart disease, while no such evidence was
      found for alpha-tocopherol as supplement. From this perspective, eating fish is
      advisable, since, for instance, a 100 g serving of salmon may provide nearly 14%
      of recommended dietary allowance.

PMID- 24915327
TI  - New Trends and Technological Challenges in the Industrial Production and
      Purification of Fructo-oligosaccharides.
AB  - An increased commercial interest in fructo-oligosaccharides (FOS) has emerged in
      the last decade due to their prebiotic activity. At large scale, the FOS are
      produced by microbial enzymes from sucrose. A mixture of FOS and other
      saccharides is obtained in this process. The presence of such saccharides reduces
      the prebiotic, caloric, and cariogenic value of the final product. Therefore,
      many efforts have been conducted to obtain a product with increased FOS purity.
      This review comprises the most important technological and physicochemical
      aspects including FOS production and recovery processes; safety, dose and health
      claims concerning its intake; and commercially available FOS. 

PMID- 24915328
TI  - A Critical Review about the Health Risk Assessment of PAHs and Their Metabolites
      in Foods.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a family of toxicants that are
      ubiquitous in the environment. These contaminants generate considerable interest,
      because some of them are highly carcinogenic in laboratory animals and have been
      implicated in breast, lung, and colon cancers in humans. Dietary intake of PAHs
      constitutes a major source of exposure in humans. Factors affecting the
      accumulation of PAHs in the diet, their absorption following ingestion, and
      strategies to assess risk from exposure to these hydrocarbons following ingestion
      have received very little attention. This review, therefore, focuses on
      concentrations of PAHs in widely consumed dietary ingredients along with
      gastrointestinal absorption rates in humans. Metabolism and bioavailability of
      PAHs in animal models and the processes, which influence the disposition of these
      chemicals, are discussed. Finally, based on intake, disposition, and
      tumorigenesis data, the exposure risk to PAHs from diet is presented. This
      information is expected to provide a framework for refinements in risk assessment
      of PAHs. 

PMID- 24915329
TI  - The role of alginates in regulation of food intake and glycemia: a
      gastroenterological perspective.
AB  - Regulation of food intake through modulation of gastrointestinal responses to
      ingested foods is an ever-growing component of the therapeutic approaches
      targeting the obesity epidemic. Alginates, viscous and gel-forming soluble fibers
      isolated from the cell wall of brown seaweeds and some bacteria, are recently
      receiving considerable attention because of their potential role in satiation,
      satiety, and food intake regulation in the short term. Enhancement of gastric
      distension, delay of gastric emptying, and attenuation of postprandial glucose
      responses may constitute the basis of their physiological benefits. Offering
      physical, chemical, sensorial, and physiological advantages over other viscous
      and gel-forming fibers, alginates constitute promising functional food
      ingredients for the food industry. Therefore, the current review explores the
      role of alginates in food intake and glycemic regulation, their underlying modes
      of action and their potential in food applications. 

PMID- 24915330
TI  - A mechanistic perspective on process-induced changes in glucosinolate content in
      Brassica vegetables: a review.
AB  - Brassica vegetables are consumed mostly after processing, which is expected to
      give beneficial effects on the vegetable properties, such as improved
      palatability and bioavailability of nutrients, or shelf life extension. But
      processing also results to various changes in the content of health promoting
      phytochemicals like glucosinolates. This paper reviews the effects of processing
      on the glucosinolates content by using a mechanism approach underlying processing
      method employed. Cultural differences between Eastern and Western preparation
      practices and their possible effect on glucosinolate retention are highlighted.
      Boiling and blanching considerably reduce the glucosinolate content mainly due to
      mechanisms of cell lysis, diffusion, and leaching, and partly due to thermal and
      enzymatic degradation. Steaming, microwave processing, and stir frying either
      retain or slightly reduce the glucosinolates content due to low degrees of
      leaching; moreover, these methods seem to enhance extractability of
      glucosinolates from the plant tissue. Fermentation reduces the glucosinolate
      content considerably, but the underlying mechanisms are not yet studied in
      detail. Studying the changes of glucosinolates during processing by a mechanistic
      approach is shown to be valuable to understand the impact of processing and to
      optimize processing conditions for health benefits of these compounds.

PMID- 24915332
TI  - Principles and limitations of stable isotopes in differentiating organic and
      conventional foodstuffs: 1. Plant products.
AB  - Among the lighter elements having two or more stable isotopes (H, C, N, O, S),
      delta(15)N appears to be the most promising isotopic marker to differentiate
      plant products from conventional and organic farms. Organic plant products vary
      within a range of delta(15)N values of +0.3 to +14.6%, while conventional plant
      products range from negative to positive values, i.e. -4.0 to +8.7%. The main
      factors affecting delta(15)N signatures of plants are N fertilizers, biological
      N2 fixation, plant organs and plant age. Correlations between mode of production
      and delta(13)C (except greenhouse tomatoes warmed with natural gas) or delta(34)S
      signatures have not been established, and delta(2)H and delta(18)O are unsuitable
      markers due to the overriding effect of climate on the isotopic composition of
      plant-available water. Because there is potential overlap between the delta(15)N
      signatures of organic and conventionally produced plant products, delta(15)N has
      seldom been used successfully as the sole criterion for differentiation, but when
      combined with complementary analytical techniques and appropriate statistical
      tools, the probability of a correct identification increases. The use of organic
      fertilizers by conventional farmers or the marketing of organic produce as
      conventional due to market pressures are additional factors confounding correct
      identification. The robustness of using delta(15)N to differentiate mode of
      production will depend on the establishment of databases that have been verified
      for individual plant products. 

PMID- 24915331
TI  - Vitamin D bioavailability: state of the art.
AB  - There has been renewed interest in vitamin D since numerous recent studies have
      suggested that besides its well-established roles in bone metabolism and
      immunity, vitamin D status is inversely associated with the incidence of several
      diseases, e.g., cancers, cardio-vascular diseases, and neurodegenerative
      diseases. Surprisingly, there is very little data on factors that affect
      absorption of this fat-soluble vitamin, although it is acknowledged that dietary
      vitamin D could help to fight against the subdeficient vitamin D status that is
      common in several populations. This review describes the state of the art
      concerning the fate of vitamin D in the human upper gastrointestinal tract and on
      the factors assumed to affect its absorption efficiency. The main conclusions
      are: (i) ergocalciferol (vitamin D2), the form mostly used in supplements and
      fortified foods, is apparently absorbed with similar efficiency to
      cholecalciferol (vitamin D3, the main dietary form), (ii) 25-hydroxyvitamin D
      (25OHD), the metabolite produced in the liver, and which can be found in foods,
      is better absorbed than the nonhydroxy vitamin D forms cholecalciferol and
      ergocalciferol, (iii) the amount of fat with which vitamin D is ingested does not
      seem to significantly modify the bioavailability of vitamin D3, (iv) the food
      matrix has apparently little effect on vitamin D bioavailability, (v) sucrose
      polyesters (Olestra) and tetrahydrolipstatin (orlistat) probably diminish vitamin
      D absorption, and (vi) there is apparently no effect of aging on vitamin D
      absorption efficiency. We also find that there is insufficient, or even no data
      on the following factors suspected of affecting vitamin D bioavailability: (i)
      effect of type and amount of dietary fiber, (ii) effect of vitamin D status, and
      (iii) effect of genetic variation in proteins involved in its intestinal
      absorption. In conclusion, further studies are needed to improve our knowledge of
      factors affecting vitamin D absorption efficiency. Clinical studies with labeled
      vitamin D, e.g., deuterated or (13)C, are needed to accurately and definitively
      assess the effect of various factors on its bioavailability. 

PMID- 24915333
TI  - An Updated Review of Meat Authenticity Methods and Applications.
AB  - Adulteration of foods is a serious economic problem concerning most foodstuffs,
      and in particular meat products. Since high-priced meat demand premium prices,
      producers of meat-based products might be tempted to blend these products with
      lower cost meat. Moreover, the labeled meat contents may not be met. Both types
      of adulteration are difficult to detect and lead to deterioration of product
      quality. For the consumer, it is of outmost importance to guarantee both
      authenticity and compliance with product labeling. The purpose of this article is
      to review the state of the art of meat authenticity with analytical and
      immunochemical methods with the focus on the issue of geographic origin and
      sensory characteristics. This review is also intended to provide an overview of
      the various currently applied statistical analyses (multivariate analysis (MAV),
      such as principal component analysis, discriminant analysis, cluster analysis,
      etc.) and their effectiveness for meat authenticity. 

PMID- 24915335
TI  - Status of bioactive compounds in foods, with focus on fruits and vegetables.
AB  - Components of cereals, legumes, pulses, proteins, sea food, milk, carbohydrates
      and lipids are being evaluated for their influence on human health, as
      biofunctional compounds. However, references dealing with fruits and vegetables
      exceed any other food group and accordingly their focus. Fruits and vegetables
      abound in a spectacular range of such health influencing compounds and thus,
      study of their bioactivity, in lieu of their consumption in fresh or processed
      form. Anti-cancerous phenolics from Phyllanthus, radioprotective Litchi
      phenolics/flavonoids, hypoglycemic Sygium, quercitin and hydroxyl cinnamates of
      Sweet cherries, xanthones of Mangosteen, ellagitannins of Pomegranate, ursolic
      acid of Sea buckthorn, muscle relaxative watermelon, anti-cholesterolemic soluble
      fibre and sterols, cardioprotective saponins, ACE-inhibitory potato hydrolysates,
      anti-pancreatic cancerous ascorbic acid, carotenoids including pro-vitamin A are
      few examples unraveled. Thus, the imminent scope to obviate their structural
      chemistry, influence on storage and processing conditions, factors favoring their
      bio-accessibility/bio-availability in the food formulations, influencing human
      health. It is the meticulous combination of these compounds in daily consumption
      that determines their usefulness to human body. What is of paramount importance
      is the actual health benefits accrued from consumption of such functional-
      compound based fresh/processed fruits,vegetables or other foods. 

PMID- 24915334
TI  - Food Safety in Feeding Services: A Requirement in Brazil.
AB  - Access to food that is adequate in both quantity and quality is directly related
      to the health of a population. Unsafe food may cause an individual to experience
      varying degrees of illnesses known as food-borne disease. As their daily lives
      change, an increasing number of Brazilian people eat outside of their houses in
      restaurants, cafes, bakeries, and other dining establishments. Until August 2004,
      food services in Brazil followed the same standards recommended for other
      industries; these standards were determined by the Ministry of Health through
      Decree 326 in 1997 and completed in 2002 by the Brazilian Health Surveillance
      Agency through Resolution 275. On September 15, 2004, the Brazilian Health
      Surveillance Agency published RDC 216 that provided information about Technical
      Regulation of Good Practices specifically for food services. This legislation
      ensures safe production of the food at Brazilian food service sites through good
      practices and procedures. The purpose of this review is to describe the aspects
      related to safe food production and to discuss the main legislation for food
      services in Brazil. 

PMID- 24915336
TI  - Types and characteristics of drinking water for hydration in the elderly.
AB  - The role of hydration in the maintenance of health is increasingly recognized.
      Hydration requirements vary for each person, depending on physical activity,
      environmental conditions, dietary patterns, alcohol intake, health problems, and
      age. Elderly individuals have higher risk of developing dehydration than adults.
      Diminution of liquid intake and increase in liquid losses are both involved in
      causing dehydration in the elderly. The water used for drinking is provided
      through regular public water supply and the official sanitary controls ensure
      their quality and hygiene, granting a range of variation for most of its physical
      and chemical characteristics, being sometimes these differences, though
      apparently small, responsible for some disorders in sensitive individuals. Hence,
      the advantages of using bottled water, either natural mineral water or spring
      water, are required by law to specify their composition, their major components,
      and other specific parameters. It is essential to take this into account to
      understand the diversity of indications and favorable effects on health that
      certain waters can offer. 

PMID- 24915337
TI  - Fructo-oligosaccharides: Production, Purification and Potential Applications.
AB  - The nutritional and therapeutic benefits of prebiotics have attracted the keen
      interest of consumers and food processing industry for their use as food
      ingredients. Fructo-oligosaccharides (FOS), new alternative sweeteners,
      constitute 1-kestose, nystose, and 1-beta-fructofuranosyl nystose produced from
      sucrose by the action of fructosyltransferase from plants, bacteria, yeast, and
      fungi. FOS has low caloric values, non-cariogenic properties, and help gut
      absorption of ions, decrease levels of lipids and cholesterol and bifidus
      stimulating functionality. The purified linear fructose oligomers are added to
      various food products like cookies, yoghurt, infant milk products, desserts, and
      beverages due to their potential health benefits. This review is focused on the
      various aspects of biotechnological production, purification and potential
      applications of fructo-oligosaccharides. 

PMID- 24915338
TI  - The Occurrence, Fate and Biological Activities of C-glycosyl Flavonoids in the
      Human Diet.
AB  - The human diet contains a wide variety of plant-derived flavonoids, many of which
      are glycosylated via an O- or less commonly a C-glycosidic linkage. The
      distribution, quantity, and biological effects of C-glycosyl flavonoids in the
      human diet have received little attention in the literature in comparison to
      their O-linked counterparts, however, despite being present in many common
      foodstuffs. The structural nature, nomenclature, and distribution of C-glycosyl
      flavonoids in the human diet are, therefore, reviewed. Forty-three dietary
      flavonoids are revealed to be C-glycosylated, arising from the dihydrochalcone,
      flavone, and flavan-3-ol backbones, and distributed among edible fruits, cereals,
      leaves, and stems. C-linked sugar groups are shown to include arabinose,
      galactose, glucose, rutinose, and xylose, often being present more than once on a
      single flavonoid backbone and occasionally in tandem with O-linked glucose or
      rutinose groups. The pharmacokinetic fate of these compounds is discussed with
      particular reference to their apparent lack of interaction with hydrolytic
      mechanisms known to influence the fate of O-glycosylated dietary flavonoids,
      explaining the unusual but potentially important appearance of intact C
      glycosylated flavonoid metabolites in human urine following oral administration.
      Finally, the potential biological significance of these compounds is reviewed,
      describing mechanisms of antidiabetic, antiinflammatory, anxiolytic,
      antispasmodic, and hepatoprotective effects. 

PMID- 24915339
TI  - Effect of dietary fiber on properties and acceptance of meat products: a review.
AB  - Meat is an important source of all essential nutritional components of our daily
      diet as it content most of the essential amino acids, fatty acids, vitamins, and
      minerals which are lack in plant based food, but it is devoid of dietary fiber,
      which is very essential component for normal physiological/biochemical process.
      During meat products processing, its functional values can be improved by
      supplementation of dietary fiber rich vegetative substances like cereal and pulse
      flour, vegetable and fruits pulp, etc. by this process, a significant proportion
      of required daily allowance of dietary fiber can be fulfilled for the frequent
      meat consumers. The consumption of meat products fortified with of dietary fiber
      can lead to the prevention of diseases like coronary heart disease, diabetes,
      irritable bowel disease, obesity, etc. On the other hand, the dietary fiber can
      effectively be incorporated in the processed meat products as binders, extender,
      and filler, they can significantly replace the unhealthy fat components from the
      products; increase acceptability by improving nutritional components, pH, water
      holding capacity, emulsion stability, shear press value, sensory characters, etc.
      of finished products. Addition of dietary fiber in the meat products can increase
      the cooking yield therefore the economic gain as well. 

PMID- 24915340
TI  - Nutrition and health - transforming research traditions.
AB  - In this contribution, we show that current scientific methodologies used in
      nutrition science and by regulatory agencies, such as the randomized control
      trial, limit our understanding of nutrition and health as they are to crude to
      capture the subtle pleiotropic nature of most nutrients. Thereby, regulatory
      agencies such as the European Food Safety Authority curb the development of
      scientific knowledge and industrial innovations within the nutritional field. In
      order to develop insights into the health impact of certain food and food
      components, we need to realize that health is adaptation set within a homeostatic
      range. Increased performance of health, i.e., the maximum stimulation of health,
      typically seems 30-60% greater than the control group, with a width of no more
      than about a factor of ten, clarifying the difficulty of documenting responses of
      food-endogenous components within the homeostatic range of healthy people. A
      strategy to record subtle responses of food components is the summation of
      procentual effects of relevant health outcomes. We illustrate this approach with
      the action of flavanols on vascular health, specifically endothelial function. 

PMID- 24915341
TI  - Effect of acid hydrolysis on starch structure and functionality: a review.
AB  - Acid hydrolysis is an important chemical modification that can significantly
      change the structural and functional properties of starch without disrupting its
      granular morphology. A deep understanding of the effect of acid hydrolysis on
      starch structure and functionality is of great importance for starch scientific
      research and its industrial applications. During acid hydrolysis, amorphous
      regions are hydrolyzed preferentially, which enhances the crystallinity and
      double helical content of acid hydrolyzed starch. This review discusses current
      understanding of the effect of acid hydrolysis on starch structure and
      functionality. The effects of acid hydrolysis on amylose content, chain length
      distribution of amylopectin molecules, molecular and crystalline organization
      (including lamellar structure) and granular morphology are considered. Functional
      properties discussed include swelling power, gelatinization, retrogradation,
      pasting, gel texture, and in vitro enzyme digestibility. The paper also
      highlights some promising applications of acid hydrolyzed starch (starch
      nanocrystals) in the preparation of biodegradable nanocomposites, bio-hydrogen,
      and slowly digestible starch-based healthy foods. 

PMID- 24915342
TI  - Potential of membrane distillation for production of high quality fruit juice
      concentrate.
AB  - Fruit juices are generally concentrated in order to improve the stability during
      storage and to reduce handling, packaging, and transportation costs. Thermal
      evaporation is the most widely used technique in industrial fruit juice
      concentrate production. In addition to high energy consumption, a large part of
      the characteristics determining the quality of the fresh juice including aroma,
      color, vitamins, and antioxidants undergoes remarkable alterations through the
      use of high operation temperatures. Increasing consumer demand for minimally or
      naturally processed stable products able to retain as much possible the
      uniqueness of the fresh fruit has engendered a growing interest for development
      of nonthermal approaches for fruit juice concentration. Among them, membrane
      distillation (MD) and its variants have attracted much attention for allowing
      very high concentrations to be reached under atmospheric pressure and
      temperatures near ambient temperature. This review will provide an overview of
      the current status and recent developments in the use of MD for concentration of
      fruit juices. In addition to the most basic concepts of MD variants, crucial
      suggestions for membrane selection and operating parameters will be presented.
      Challenges and future trends for industrial adaptation taking into account the
      possibility of integrating MD with other existing processes will be discussed. 

PMID- 24915343
TI  - Maintaining antioxidant potential of fresh fruits and vegetables after harvest.
AB  - The consumption of fruits and vegetables has increased in the past few years, not
      only because of their attractive sensorial properties, but also for their
      nutritional and health benefits. Antioxidants are compounds found in fresh fruits
      and vegetables, and evidence of their role in the prevention of degenerative
      diseases is continuously emerging. However, the antioxidants in some fruits and
      vegetables can be lost during handling after harvest, even during minimal
      processing and storage. In this sense, postharvest treatments are needed to
      preserve the quality and antioxidant potential of fresh produce. Postharvest
      treatments and technologic strategies (including ultraviolet light, controlled
      and modified atmospheres, heat treatments, and application of natural compounds,
      such as edible coatings, active packaging, microencapsulation, and nanoemulsion)
      have shown positive and promising results to maintain fruit and vegetable
      antioxidant potential. The purpose of this review is to analyze and propose the
      application of postharvest strategies to maintain, or even improve, the
      antioxidant status of fruits and vegetables, thus offering options to maximize
      health benefits to consumers.

PMID- 24915344
TI  - Membrane processing technology in the food industry: food processing, wastewater
      treatment, and effects on physical, microbiological, organoleptic, and
      nutritional properties of foods.
AB  - Membrane processing technology (MPT) is increasingly used nowadays in a wide
      range of applications (demineralization, desalination, stabilization, separation,
      deacidification, reduction of microbial load, purification, etc.) in food
      industries. The most frequently applied techniques are electrodialysis (ED),
      reverse osmosis (RO), nanofiltration (NF), ultrafiltration (UF), and
      microfiltration (MF). Several membrane characteristics, such as pore size, flow
      properties, and the applied hydraulic pressure mainly determine membranes'
      potential uses. In this review paper the basic membrane techniques, their
      potential applications in a large number of fields and products towards the food
      industry, the main advantages and disadvantages of these methods, fouling
      phenomena as well as their effects on the organoleptic, qualitative, and
      nutritional value of foods are synoptically described. Some representative
      examples of traditional and modern membrane applications both in tabular and
      figural form are also provided. 

PMID- 24915345
TI  - Bioactive substances from marine fishes, shrimps, and algae and their functions:
      present and future.
AB  - Marine fishes, shrimps, and algae have many important bioactive substances, such
      as peptides, unsaturated fatty acids, polysaccharides, trace elements, and
      natural pigments. The introduction of these substances contributes to a
      significant improvement in developing them in final processed products. In fact,
      the knowledge of these bioactive substances has experienced a rapid increase in
      the past 20 years and prompted the relevant technological revolution with a
      decisive contribution to the final application. The purpose of this review was to
      introduce critically and comprehensively the present knowledge of these bioactive
      substances and pointed out their future developmental situation.

PMID- 24915346
TI  - The content of polyphenolic compounds in cocoa beans (Theobroma cacao L.),
      depending on variety, growing region, and processing operations: a review.
AB  - Polyphenols form the largest group of compounds among natural antioxidants, which
      largely affect the overall antioxidant and anti-free radical activity of cocoa
      beans. The qualitative and quantitative composition of individual fractions of
      polyphenolic compounds, even within one species, is very diverse and depends on
      many factors, mainly on the area of cocoa trees cultivation, bean maturity,
      climatic conditions during growth, and the harvest season and storage time after
      harvest. Thermal processing of cocoa beans and cocoa derivative products at
      relatively high temperatures may in addition to favorable physicochemical,
      microbiological, and organoleptic changes result in a decrease of polyphenols
      concentration. Technological processing of cocoa beans negatively affects the
      content of polyphenolic compounds.

PMID- 24915347
TI  - Chickpeas-composition, nutritional value, health benefits, application to bread
      and snacks: a review.
AB  - Chickpea is grain legumes grown mainly in areas with temperate and semiarid
      climate. It is characterized by a high content of protein, fat, vitamins, fiber,
      and a lower content of carbohydrates than flour of wheat. Chickpeas may contain
      antinutritional compounds that can impair utilization of the nutrients by people.
      Heat treatment is an effective method to increase the amount of protein available
      for intestinal digestibility. Adding chickpeas to a foodstuff can increase their
      nutritional value and reduce the acrylamide content. Acrylamide is an
      antinutritional substance present in foods, such as bread, snacks, and chips.
      Chickpea flour and protein may be new way to a reduce the content of acrylamide
      in products of this type. The addition of chickpea flour affects the sensory and
      textural properties. 

PMID- 24915348
TI  - BPA, an energy balance disruptor.
AB  - Bisphenol A (BPA) is used extensively in the world and is present in a diverse
      range of manufactured articles including dental resins, polycarbonate plastics,
      and the inner coating of food cans. It is a high volume chemical, with global
      production at 3.6 * 10(9) kg per year. BPA was identified as a high priority for
      assessment of human health risk because it was considered to present greatest
      potential for human exposure. Most studies of the health effects of BPA have
      focused on endocrine disruption leading to reproductive toxicity, but it displays
      additional side effects, including liver damage, disrupted pancreatic beta-cell
      function, thyroid hormone disruption, and obesity-promoting effects. In this
      article, we reviewed specifically on the effects of BPA in energy balance.

PMID- 24915349
TI  - Umami taste components and their sources in Asian foods.
AB  - Umami, the fifth basic taste, is the inimitable taste of Asian foods. Several
      traditional and locally prepared foods and condiments of Asia are rich in umami.
      In this part of world, umami is found in fermented animal-based products such as
      fermented and dried seafood, and plant-based products from beans and grains, dry
      and fresh mushrooms, and tea. In Southeast Asia, the most preferred seasonings
      containing umami are fish and seafood sauces, and also soybean sauces. In the
      East Asian region, soybean sauces are the main source of umami substance in the
      routine cooking. In Japan, the material used to obtain umami in dashi, the stock
      added to almost every Japanese soups and boiled dishes, is konbu or dried bonito.
      This review introduces foods and seasonings containing naturally high amount of
      umami substances of both animal and plant sources from different countries in
      Asia.

PMID- 24915350
TI  - Tea and its consumption: benefits and risks.
AB  - The recent convention of introducing phytochemicals to support the immune system
      or combat diseases is a centuries' old tradition. Nutritional support is an
      emerging advancement in the domain of diet-based therapies; tea and its
      constituents are one of the significant components of these strategies to
      maintain the health and reduce the risk of various malignancies. Tea is the most
      frequently consumed beverage worldwide, besides water. All the three most popular
      types of tea, green (unfermented), black (fully fermented), and oolong
      (semifermented), are manufactured from the leaves of the plant Camellia sinensis.
      Tea possesses significant antioxidative, anti-inflammatory, antimicrobial,
      anticarcinogenic, antihypertensive, neuroprotective, cholesterol-lowering, and
      thermogenic properties. Several research investigations, epidemiological studies,
      and meta-analyses suggest that tea and its bioactive polyphenolic constituents
      have numerous beneficial effects on health, including the prevention of many
      diseases, such as cancer, diabetes, arthritis, cardiovascular disease (CVD),
      stroke, genital warts, and obesity. Controversies regarding beneficialts and
      risks of tea consumption still exist but the limitless health-promoting benefits
      of tea outclass its few reported toxic effects. However, with significant rise in
      the scientific investigation of role of tea in human life, this review is
      intended to highlight the beneficial effects and risks associated with tea
      consumption. 

PMID- 24915351
TI  - Significance of nutrition in pulmonary tuberculosis.
AB  - Malnutrition and tuberculosis are both problems mostly of the developing
      countries. Tuberculosis can lead to malnutrition and malnutrition may predispose
      to tuberculosis. Poor nutrition leads to protein-energy malnutrition and
      micronutrients deficiencies which lead to immunodeficiency. This secondary
      immunodeficiency increases the host's susceptibility to infection and hence
      increase the risk for developing tuberculosis. Tuberculosis itself leads to
      reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and
      altered metabolism leading to wasting and poor nutritional status. Nutritional
      status and dietary intake and hence nutritional status of patients get improved
      during antituberculosis treatment. 

PMID- 24915352
TI  - Application of membrane separation in fruit and vegetable juice processing: a
      review.
AB  - Fruit and vegetable juices are used due to convenience. The juices are rich in
      various minerals, vitamins, and other nutrients. To process the juices and their
      clarification and/or concentration is required. The membranes are being used for
      these purposes. These processes are preferred over others because of high
      efficiency and low temperature. Membranes and their characteristics have been
      discussed in brief for knowing suitability of membranes for fruit and vegetable
      juices. Membrane separation is low temperature process in which the organoleptic
      quality of the juice is almost retained. In this review, different membrane
      separation methods including Microfiltration, Ultrafiltration, and Reverse
      osmosis for fruit juices reported in the literature are discussed. The major
      fruit and vegetable juices using membrane processes are including the Reverse
      osmosis studies for concentration of Orange juice, Carrot juice, and Grape juice
      are discusses. The Microfiltration and Ultrafiltration are used for clarification
      of juices of mosambi juice, apple juice, pineapple juice, and kiwifruit juice.
      The various optimized parameters in membranes studies are pH, TAA, TSS, and AIS.
      In this review, in addition to above the OD is also discussed, where the
      membranes are used. 

PMID- 24915354
TI  - Green tea and anticancer perspectives: updates from last decade.
AB  - Green tea is the most widely consumed beverage besides water and has attained
      significant attention owing to health benefits against array of maladies, e.g.,
      obesity, diabetes mellitus, cardiovascular disorders, and cancer insurgence. The
      major bioactive molecules are epigallocatechin-3-gallate, epicatechin,
      epicatechin-3-gallate, epigallocatechin, etc. The anticarcinogenic and
      antimutagenic activities of green tea were highlighted some years ago. Several
      cohort studies and controlled randomized trials suggested the inverse association
      of green tea consumption and cancer prevalence. Cell culture and animal studies
      depicted the mechanisms of green tea to control cancer insurgence, i.e.,
      induction of apoptosis to control cell growth arrest, altered expression of cell
      cycle regulatory proteins, activation of killer caspases, and suppression of
      nuclear factor kappa-B activation. It acts as carcinoma blocker by modulating the
      signal transduction pathways involved in cell proliferation, transformation,
      inflammation, and metastasis. However, results generated from some research
      interventions conducted in different groups like smokers and nonsmokers, etc.
      contradicted with aforementioned anticancer perspectives. In this review paper,
      anticancer perspectives of green tea and its components have been described.
      Recent findings and literature have been surfed and arguments are presented to
      clarify the ambiguities regarding anticancer perspectives of green tea and its
      component especially against colon, skin, lung, prostate, and breast cancer. The
      heading of discussion and future trends is limelight of the manuscript. The
      compiled manuscript provides new avenues for researchers to be explored in
      relation to green tea and its bioactive components. 

PMID- 24915355
TI  - Effects of sugar concentration processes in grapes and wine aging on aroma
      compounds of sweet wines-a review.
AB  - Dessert sweet wines from Europe and North America are described in this review
      from two points of view: both their aroma profile and also their sensorial
      description. There are growing literature data about the chemical composition and
      sensory properties of these wines. Wines were grouped according to the production
      method (concentration of sugars in grapes) and to the aging process of wine
      (oxidative, biological, or a combination of both and aging in the bottle). It was
      found that wines natively sweets and wines fortified with liquors differ in their
      volatile compounds. Sensory properties of these wines include those of dried
      fruit (raisins), red berries, honey, chocolate and vanilla, which is contributing
      to their growing sales. However, there is still a need for scientific research on
      the understanding of the mechanisms for wine flavor enhancement. 

PMID- 24915353
TI  - Portion size: what we know and what we need to know.
AB  - There is increasing evidence that the portion sizes of many foods have increased
      and in a laboratory at least this increases the amount eaten. The conclusions
      are, however, limited by the complexity of the phenomenon. There is a need to
      consider meals freely chosen over a prolonged period when a range of foods of
      different energy densities are available. A range of factors will influence the
      size of the portion size chosen: amongst others packaging, labeling, advertising,
      and the unit size rather than portion size of the food item. The way portion size
      interacts with the multitude of factors that determine food intake needs to be
      established. In particular, the role of portion size on energy intake should be
      examined as many confounding variables exist and we must be clear that it is
      portion size that is the major problem. If the approach is to make a practical
      contribution, then methods of changing portion sizes will need to be developed.
      This may prove to be a problem in a free market, as it is to be expected that
      customers will resist the introduction of smaller portion sizes, given that value
      for money is an important motivator. 

PMID- 24915356
TI  - Spray drying of fruit and vegetable juices--a review.
AB  - The main cause of spray drying is to increase the shelf life and easy handling of
      juices. In the present paper, the studies carried out so far on spray drying of
      various fruits and vegetables are reported. The major fruit juices dried are
      mango, banana, orange, guava, bayberry, watermelon, pineapple, etc. However,
      study on vegetable juices is limited. In spray drying, the major optimized
      parameters are inlet air temperature, relative humidity of air, outlet air
      temperature, and atomizer speed that are given for a particular study. The juices
      in spray drying require addition of drying agents that include matlodextrin,
      liquid glucose, etc. The drying agents are added to increase the glass transition
      temperature. Different approaches for spray dryer design have also been discussed
      in the present work. 

PMID- 24915358
TI  - Cocoa agronomy, quality, nutritional, and health aspects.
AB  - The history of cocoa and chocolate including the birth and the expansion of the
      chocolate industry was described. Recent developments in the industry and cocoa
      economy were briefly depicted. An overview of the classification of cacao as well
      as studies on phenotypic and genetic diversity was presented. Cocoa agronomic
      practices including traditional and modern propagation techniques were reviewed.
      Nutrition-related health benefits derived from cocoa consumption were listed and
      widely reviewed. The specific action of cocoa antioxidants was compared to those
      of teas and wines. Effects of adding milk to chocolate and chocolate drinks
      versus bioavailability of cocoa polyphenols were discussed. Finally, flavor,
      sensory, microbiological, and toxicological aspects of cocoa consumption were
      presented. 

PMID- 24915357
TI  - Recent development in osmotic dehydration of fruit and vegetables: a review.
AB  - Osmotic dehydration of fruits and vegetables is achieved by placing the
      solid/semi solid, whole or in pieces, in a hypertonic solution (sugar and/or
      salt) with a simultaneous counter diffusion of solutes from the osmotic solution
      into the tissues. Osmotic dehydration is recommended as a processing method to
      obtain better quality of food products. Partial dehydration allows structural,
      nutritional, sensory, and other functional properties of the raw material to be
      modified. However, the food industry uptake of osmotic dehydration of foods has
      not been extensive as expected due to the poor understanding of the counter
      current flow phenomena associated with it. However, these flows are in a dynamic
      equilibrium with each other and significantly influence the final product in
      terms of preservation, nutrition, and organoleptic properties. The demand of
      healthy, natural, nutritious, and tasty processed food products continuously
      increases, not only for finished products, but also for ingredient to be included
      in complex foods such as ice cream, cereals, dairy, confectionaries, and bakery
      products. 

PMID- 24915359
TI  - State of polyphenols in the drying process of fruits and vegetables.
AB  - This review presents an overview of drying technologies and its impact on the
      polyphenol content of vegetables and fruits. Polyphenols contribute to many
      health benefits and can act as antioxidants. Specifically an increased intake of
      polyphenols has been shown to decrease the incidence of cardiovascular disease;
      furthermore, it has been shown to help reduce the risk of neurodegenerative
      diseases in humans. Many researchers have reported on the effect of different
      drying techniques on the polyphenol content in fruits and vegetables. Polyphenol
      degradation mechanisms proposed in literature and pretreatments that potentially
      lead to higher retention of polyphenols during drying are also discussed. 

PMID- 24915360
TI  - Mung bean: technological and nutritional potential.
AB  - Mung bean (Vigna radiata (L.) R. Wilczek) has been intensively researched;
      scattered data are available on various properties. Data on physical, chemical,
      food processing, and nutritional properties were collected for whole mung bean
      grains and reviewed to assess the crop's potential as food and to set research
      priorities. Results show that mung bean is a rich source of protein (14.6-33.0
      g/100 g) and iron (5.9-7.6 mg/100 g). Grain color is correlated with compounds
      like polyphenols and carotenoids, while grain hardness is associated with fiber
      content. Physical properties like grain dimensions, sphericity, porosity, bulk,
      and true density are related to moisture content. Anti-nutrients are phytic acid,
      tannins, hemagglutinins, and polyphenols. Reported nutrient contents vary
      greatly, the causes of which are not well understood. Grain size and color have
      been associated with different regions and were used by plant breeders for
      selection purposes. Analytical methods require more accuracy and precision to
      distinguish biological variation from analytical variation. Research on nutrient
      digestibility, food processing properties, and bioavailability is needed.
      Furthermore, the effects of storage and processing on nutrients and food
      processing properties are required to enable optimization of processing steps,
      for better mung bean food quality and process efficiency.

PMID- 24915361
TI  - Advances in research on cis-9, trans-11 conjugated linoleic acid: a major
      functional conjugated linoleic acid isomer.
AB  - Conjugated linoleic acid (CLA) consists of a group of positional and geometric
      conjugated isomers of linoleic acid. Since the identification of CLA as a factor
      that can inhibit mutagenesis and carcinogenesis, thousands of studies have been
      conducted in the last several decades. Among the many isomers discovered, cis-9,
      trans-11 CLA is the most intensively studied because of its multiple, isomer
      specific effects in humans and animals. This paper provides an overview of the
      available data on cis-9, trans-11 CLA, including its isomer-specific effects,
      biosynthesis, in vivo/in vitro research models, quantification, and the factors
      influencing its content in ruminant products. 

PMID- 24915362
TI  - Scope of millet grains as an extender in meat products.
AB  - India stood first for millet production in the world and plays a significant role
      in meat production and consumption too. To meet the demand of health conscious
      consumers for healthy and nutritious meat food item, the incorporation of millet
      grains and its byproducts to the meat products by the processors can serve the
      purpose. The multidimensional positive nutritional and functional characteristics
      millet grain not only improve the acceptability of the meat products but also
      increase its own demand as a main coarse food grain in competition to the wheat
      and rice over the world.

PMID- 24915363
TI  - Stress responses in probiotic Lactobacillus casei.
AB  - Survival in harsh environments is critical to both the industrial performance of
      lactic acid bacteria (LAB) and their competitiveness in complex microbial
      ecologies. Among the LAB, members of the Lactobacillus casei group have
      industrial applications as acid-producing starter cultures for milk fermentations
      and as specialty cultures for the intensification and acceleration of flavor
      development in certain bacterial-ripened cheese varieties. They are amongst the
      most common organisms in the gastrointestinal (GI) tract of humans and other
      animals, and have the potential to function as probiotics. Whether used in
      industrial or probiotic applications, environmental stresses will affect the
      physiological status and properties of cells, including altering their
      functionality and biochemistry. Understanding the mechanisms of how LAB cope with
      different environments is of great biotechnological importance, from both a
      fundamental and applied perspective: hence, interaction between these strains and
      their environment has gained increased interest in recent years. This paper
      presents an overview of the important features of stress responses in Lb. casei,
      and related proteomic or gene expression patterns that may improve their use as
      starter cultures and probiotics.

PMID- 24915364
TI  - Effects of high-pressure CO2 processing on flavor, texture, and color of foods.
AB  - High-pressure CO2 (HPCD) is a pasteurization method that inactivates
      microorganism and enzymes through molecular effects of CO2 under pressures below
      50 MPa without exposing foods to adverse effects of heat. Thermal pasteurization
      can impart undesirable changes on organoleptic and nutritional quality of the
      foods, which can reduce sensory perception and consumer acceptance of the foods.
      As a novel nonthermal processing technique, HPCD does avoid drawbacks such as
      loss of flavor, denaturation of nutrients, production of side toxic reactions, as
      well as changes in physical, mechanical, and optical properties of the food
      materials involved in the processing. This review gives a survey and analysis of
      recent publications regarding the effects of HPCD on the flavor, texture and
      color of processed foods, and possible mechanisms explaining HPCD technique on
      the flavor, texture, and color of the foods were discussed.

PMID- 24915365
TI  - A review on the fermentation of foods and the residues of pesticides
      biotransformation of pesticides and effects on fermentation and food quality.
AB  - Residues of pesticides in food are influenced by processing such as fermentation.
      Reviewing the extensive literature showed that in most cases, this step leads to
      large reductions in original residue levels in the fermented food, with the
      formation of new pesticide by-products. The behavior of residues in fermentation
      can be rationalized in terms of the physical-chemical properties of the pesticide
      and the nature of the process. In addition, the presence of pesticides decrease
      the growth rate of fermentative microbiota (yeasts and bacterias), which provokes
      stuck and sluggish fermentations. These changes have in consequence repercussions
      on several aspects of food sensory quality (physical-chemical properties,
      polyphenolic content, and aromatic profile) of fermented food. The main aim of
      this review is to deal with all these topics to propose challenging needs in
      science-based quality management of pesticides residues in food. 

PMID- 24915366
TI  - Wheat Allergy and Intolerence; Recent Updates and Perspectives.
AB  - The current review paper highlights the complicacies associated with communities
      relying on wheat as their dietary staple. Although, wheat is an important source
      of nutrients but is also linked with allergenic responses in genetically
      susceptible subjects. The wheat proteins especially alpha-amylase inhibitors,
      omega-5 gliadins, prolamins, nonprolamin, glucoprotein, and profilins are of
      significance importance. The allergenic responses are further categorized into
      IgE-mediated and non-IgE-mediated reactions. Conjugation and degranulation of the
      IgEs with the allergens results in release of several mediators. In contrary, non
      IgE-mediated wheat allergy depends on immune complexes formed by food and food
      antibodies and cell-mediated immunity. As results, different diseases tend to
      occur on the completion of these reactions, i.e., celiac disease, baker's asthma,
      diarrhea, atopic dermatitis, and urticaria. This instant paper highlighted the
      concept of food allergy with special reference to wheat. The models are developed
      that are included in this paper showing the wheat allergen, their possible
      routes, impact on human health, and indeed possible remedies. The paper would
      provide the basic information for the researchers, common man, and allied
      stakeholders to cater the issue in details. However, the issue needs the
      attention of the researchers as there is a need to clarify the issues of wheat
      allergy and wheat intolerance.

PMID- 24915368
TI  - Isolation and characterization of peptides with antihypertensive activity in
      foodstuffs.
AB  - Hypertension is one of the main causes of cardiovascular diseases. Synthetic
      drugs inhibiting ACE activity present high effectiveness in the treatment of
      hypertension but cause undesirable side effects. Unlike these synthetic drugs,
      antihypertensive peptides do not show any adverse effect. These peptides are
      naturally present in some foods and since hypertension is closely related to
      modern diet habits, the interest for this kind of foods is increasing. Different
      methods for the purification, isolation, and characterization of antihypertensive
      peptides in foods have been developed. Nevertheless, there is no revision work
      summarizing and comparing these strategies. In this review, in vivo and in vitro
      pathways to obtain antihypertensive peptides have been summarized. The ACE
      mechanism and the methodologies developed to assay the ACE inhibitory activity
      have also been described. Moreover, a comprehensive overview on the isolation,
      purification, and identification techniques focusing on the discovery of new
      antihypertensive peptides with high activity has been included. Finally, it is
      worthy to highlight that the quantitation of antihypertensive peptides in foods
      is a new trend since genotype and processing conditions could affect their
      presence. Analytical methodologies using mass spectrometry constitute an
      interesting option for this purpose. 

PMID- 24915367
TI  - Lactic acid bacteria as a cell factory for the delivery of functional
      biomolecules and ingredients in cereal-based beverages: a review.
AB  - In this review, we aim to describe the mechanisms by which LAB can fulfil the
      novel role of efficient cell factory for the production of functional
      biomolecules and food ingredients to enhance the quality of cereal-based
      beverages. LAB fermentation is a safe, economical, and traditional method of food
      preservation foremost, as well as having the additional benefits of flavor,
      texture, and nutrition amelioration. Additionally, LAB fermentation in known to
      render cereal-based foods and beverages safe, in a chemical-free, consumer
      friendly manner, from an antinutrient and toxigenic perspective. Huge market
      opportunities and potential exist for food manufacturers who can provide the
      ideal functional beverage fulfilling consumer needs. Newly developed fermented
      cereal-based beverages must address markets globally including, high-nutrition
      markets (developing countries), lifestyle choice consumers (vegetarian, vegan,
      low-fat, low-salt, low-calorie), food-related non-communicable disease sufferers
      (cardiovascular disease, diabetes), and green label consumers (Western
      countries). To fulfil these recommendations, a suitable LAB starter culture and
      cereal-based raw materials must be developed. These strains would be suitable for
      the biopreservation of cereal beverages and, ideally, would be highly antifungal,
      anti-mycotoxigenic, mycotoxin-binding and proteolytic (neutralize toxic peptides
      and release flavor-contributing amino acids) with an ability to ferment cereals,
      whilst synthesizing oligosaccharides, thus presenting a major opportunity for the
      development of safe cereal-based prebiotic functional beverages to compete with
      and replace the existing dairy versions. 

PMID- 24915370
TI  - Sugar ester surfactants: enzymatic synthesis and applications in food industry.
AB  - Sugar esters are non-ionic surfactants that can be synthesized in a single
      enzymatic reaction step using lipases. The stability and efficiency of lipases
      under unusual conditions and using non-conventional media can be significantly
      improved through immobilization and protein engineering. Also, the development of
      de novo enzymes has seen a significant increase lately under the scope of the new
      field of synthetic biology. Depending on the esterification degree and the nature
      of fatty acid and/or sugar, a range of sugar esters can be synthesized. Due to
      their surface activity and emulsifying capacity, sugar esters are promising for
      applications in food industry. 

PMID- 24915369
TI  - Genetically modified feeds in poultry diet: safety, performance, and product
      quality.
AB  - Concerns have been expressed regarding the safety of using biotechnology derived
      feeds in diets of livestock animals and in regard to human consumption of
      products from species fed transgenic crops. As a consequence, a large number of
      poultry nutrition studies have been conducted to evaluate the wholesomeness of
      transgenic crops by examining performances of animals during growth or egg
      laying. Studies also evaluated whether foreign DNA and proteins could be detected
      in meat, egg, and tissue samples from broiler chickens and laying hens fed diets
      containing transgenic feeds. In all studies, the conclusions were in agreement
      that the transgenic crops provided comparable performance, carcass and egg
      yields, and meat and egg composition, when compared with conventional grains.
      Moreover, it was demonstrated that transgenic proteins and DNA present in
      livestock feeds are not detectable in food products derived from these animals,
      using the most sensitive detection methods available, confirming that they are
      rapidly degraded by normal digestive processes. The lack of significant
      differences were a result of the similarity in nutrient composition of the
      genetically modified feeds and lack of differences in intake and digestibility,
      while there were no evidences that the differences reported for performance
      response variables and carcass measurements between treatment groups were
      attributable to the presence of the transgenic gene and protein in the
      biotechnology derived plants. Results demonstrated that genetically modified
      feeds are substantially equivalent and they result as safe as existing
      conventional feeds. 

PMID- 24915371
TI  - A review of the process-induced changes in the phytochemical content of cereal
      grains: the breadmaking process.
AB  - The importance of cereal grains in human nutrition is well documented. Especially
      the impact of whole grains consumption on human health has attracted much
      attention over the last decades. The health benefits are associated with the high
      content of cereal grains in dietary fiber but also recent research has shown that
      cereal grains are rich in bioactive compounds, which are unique in composition
      and different to phytochemicals from other sources such as fruit and vegetables.
      Cereal grains however are processed before human consumption. Depending on the
      process, the levels and the composition of the available bioactive compounds can
      be affected. Knowledge of the effect of these processes on the phytochemical
      compounds is essential to ensure the products generated are nutritious and can
      convey health benefits to the consumers. This article reviews the literature on
      the effect of milling and breadmaking processes on the levels and profile of
      bioactive compounds. Milling and breadmaking are two of the most common processes
      used universally to prepare the grains for consumption. These processes involve
      several stages and many variable factors, which can alter the levels and profile
      of the available phytochemicals in the end-product. 

PMID- 24915372
TI  - Immunological properties of inulin-type fructans.
AB  - Beneficial effects of inulin-type fructans are discussed in view of studies that
      applied the oligosaccharides in colon cancer, chronic inflammatory diseases,
      vaccination efficacy, and prevention of infection and allergy. In the present
      paper, we discuss their immunomodulating effects. It is suggested that
      immunomodulation is elicited through indirect and direct mechanisms. Indirect
      mechanisms encompass stimulation of growth and activity of lactic acid bacteria,
      but can also be caused by fermentation products of these bacteria, i.e., short
      chain fatty acids. Evidence for direct effects on the immune system generally
      remains to be confirmed. It is suggested that inulin-type fructans can be
      detected by gut dendritic cells (DCs), through receptor ligation of pathogen
      recognition receptors (PRRs) such as Toll-like receptors, nucleotide
      oligomerization domain containing proteins (NODs), C-type lectin receptors, and
      galectins, eventually inducing pro- and anti-inflammatory cytokines. DCs may also
      exert antigen presenting capacity toward effector cells, such as B cells, T
      cells, and natural killer cells locally, or in the spleen. Inulin-type fructans
      may also ligate PRRs expressed on gut epithelium, which could influence its
      barrier function. Inulin-type fructans are potent immunomodulating food
      components that hold many promises for prevention of disease. However, more
      studies into the mechanisms, dose-effect relations, and structure-function
      studies are required. 

PMID- 24915373
TI  - Mouse models of food allergy: how well do they simulate the human disorder?
AB  - Food allergy is a growing health problem with serious concerns due to high
      potential for fatality. Rapid advances in the knowledge on causes and mechanisms
      as well as in developing effective prevention/therapeutic strategies are needed.
      To meet these goals, mouse models that simulate the human disorder are highly
      desirable. During the past decade, several mouse models of food allergies have
      been reported. Here, we briefly reviewed the human disorder and then critically
      evaluated these models seeking answers to the following important questions: To
      what extent do they simulate the human disorder? What are the strengths and
      limitations of these models? What are the challenges facing this scientific area?
      Our analysis suggest that: (i) the mouse models, with inherent strengths and
      limitations, are available for many major food allergies; there is scope for
      additional model development and validation; (ii) models mostly simulate the
      severe forms of human disorder with similar immune and clinical features; (iii)
      the approaches used to develop some of the mouse models may be questionable; and
      (iv) the specific mechanisms of sensitization as wells as oral elicitation of
      fatal reactions in both humans and mice remains incompletely understood and
      therefore warrants further research. 

PMID- 24915374
TI  - Pre- and postharvest preventive measures and intervention strategies to control
      microbial food safety hazards of fresh leafy vegetables.
AB  - This review includes an overview of the most important preventive measures along
      the farm to fork chain to prevent microbial contamination of leafy greens. It
      also includes the technological and managerial interventions related to primary
      production, postharvest handling, processing practices, distribution, and
      consumer handling to eliminate pathogens in leafy greens. When the
      microbiological risk is already present, preventive measures to limit actual
      contamination events or pathogen survival are considered intervention strategies.
      In codes of practice the focus is mainly put on explaining preventive measures.
      However, it is also important to establish more focused intervention strategies.
      This review is centered mainly on leafy vegetables as the commodity identified as
      the highest priority in terms of fresh produce microbial safety from a global
      perspective. There is no unique preventive measure or intervention strategy that
      could be applied at one point of the food chain. We should encourage growers of
      leafy greens to establish procedures based on the HACCP principles at the level
      of primary production. The traceability of leafy vegetables along the chain is an
      essential element in ensuring food safety. Thus, in dealing with the food safety
      issues associated with fresh produce it is clear that a multidisciplinary farm to
      fork strategy is required. 

PMID- 24915375
TI  - Tomato (Solanum lycopersicum) Carotenoids and Lycopenes Chemistry; Metabolism,
      Absorption, Nutrition, and Allied Health Claims--A Comprehensive Review.
AB  - Tomato (Solanum lycopersicum) is one of the most essential herbaceous plants that
      have been probed against various life sight related disorders owing to array of
      phytochemicals. It is important source of vitamin C, potassium, folic acid, and
      carotenoids, such as lycopene. Carotenoids are the pigments synthesized during
      fruit ripening and responsible for the final red color of the tomato. Consumption
      of tomato and tomato-based products contribute to the absorption of carotenoids
      and lycopenes in human serum. Lycopene is chemically acyclic carotene with 11
      conjugated double bonds, normally in transconfiguration while isomerization occur
      in blood plasma for its better absorption. It has ability for adenosine deaminase
      inhibition that plays important role in the regression of tumor. Tomato also
      contain other active compounds, namely, neoxanthin, lutein, alpha-cryptoxanthin,
      alpha-carotene, beta-carotene, cyclolycopene, and beta-carotene 5, 6-epoxide.
      These components provide synergistic effect against various threats but still
      need further attention of the researchers. Both in vitro and in vivo studies have
      elucidated the potential of tomato against variety of metabolic syndromes. Latest
      research highlights the relationship between consuming tomato and its products
      with reduced risk of various maladies like obesity, hyperglycemic and
      hypercholesterolemic attributes, cardiovascular disorders, and cancer
      insurgences. Moreover, tomato and its bioactive components hold potential to
      become effective modules in diet-based regimens; however, integrated research and
      meta-analysis are still required to enhance meticulousness. 

PMID- 24915376
TI  - Cocoa and Human Health: From Head to Foot--A Review.
AB  - The cocoa, as part of the wonderful nature, provides the mankind a wide variety
      of valuable food products and health benefits. The most known and universally
      relished product derived from this fruit is chocolate, an amazing and unique food
      for the human nutrition with records of consumption of similar products dating to
      1000 years BC. In fact, the cocoa is a complex food that includes over 300
      different components. This review is designed to inform scientists, technicians,
      academicians, farmers, and interested communities of numerous studies that have
      been conducted worldwide to investigate the properties of various cocoa
      constituents, their relations to human health, and their potential role in the
      prevention and treatment of many medical conditions. The general population, for
      example in Brazil, despite being one of the major producers of cocoa, is poorly
      informed of the significant and beneficial properties of cocoa. The present
      review covers important topics linking cocoa to human health and show the state
      of the art of effect of cocoa in different systems that comprise the human body.
      The paper is organized based on the main human organ system and includes:
      cardiovascular/circulatory, neurological/nervous, oral health, endocrine,
      lymphatic and immunological, respiratory, reproductive, and dermatological
      systems. Scientific findings tend to confirm the historic designation of cocoa as
      "food of the Gods."

PMID- 24915377
TI  - Surface processing: existing and potential applications of ultraviolet light.
AB  - Solid foods represent optimal matrices for ultraviolet processing with effects
      well beyond nonthermal surface disinfection. UV radiation favors hormetic
      response in plant tissues and degradation of toxic compound on the product
      surface. Photoinduced reactions can also provide unexplored possibilities to
      steer structure and functionality of food biopolymers. The possibility to
      extensively exploit this technology will depend on availability of robust
      information about efficacious processing conditions and adequate strategies to
      completely and homogeneously process food surface. 

PMID- 24915378
TI  - Methoxypyrazine analysis and influence of viticultural and enological procedures
      on their levels in grapes, musts, and wines.
AB  - This review discusses the factors that affect the concentrations of
      methoxypyrazines (MPs) and the techniques used to analyze MPs in grapes, musts,
      and wines. MPs are commonly studied pyrazines in food science due to their
      contribution of aroma and flavor to numerous vegetables such as peas and
      asparagus. They are described as highly odorous compounds with a very low
      olfactory threshold. The grape varietals that exhibit green or herbaceous aromas
      that are characteristic of MPs are predominantly Vitis vinifera cv. Cabernet
      Sauvignon and Sauvignon Blanc, but include others. The most extensively studied
      MPs include 3-isobutyl-2-methoxypyrazine, 3-isopropyl-2-methoxypyrazine, and 3
      sec-butyl-2-methoxypyrazine. It outlines the significance of methoxypyrazines in
      grapes, musts, and wines in terms of the concentrations that are capable of
      contributing their sensory characteristics to wines. This review discusses
      methods for analyzing MPs including gas chromatography-mass spectroscopy (one or
      two dimension) and high-performance liquid chromatography, the appropriate
      extraction techniques, and the efficacy of these methods. Additionally, this
      review explores factors that affect pyrazine content of grapes, must, and wines,
      such as the effects of different viticultural practices, effects of light
      exposure and grape maturation, climate, soil, the multi-colored Asian lady beetle
      and the effects of different vinification processes. 

PMID- 24915379
TI  - Storage Stability of Food Protein Hydrolysates-A Review.
AB  - In recent years, mainly due to the specific health benefits associated with (1)
      the discovery of bioactive peptides in protein hydrolysates, (2) the reduction of
      protein allergenicity by protein hydrolysis, and (3) the improved protein
      digestibility and absorption of protein hydrolysates, the utilization of protein
      hydrolysates in functional foods and beverages has significantly increased.
      Although the specific health benefits from different hydrolysates are somewhat
      proven, the delivery and/or stability of these benefits is debatable during
      distribution, storage, and consumption. In this review, we discuss (1) the
      quality changes in different food protein hydrolysates during storage; (2) the
      resulting changes in the structure and texture of three food matrices, i.e., low
      moisture foods (LMF, aw < 0.6), intermediate moisture foods (IMF, 0.6 <= aw <
      0.85), and high moisture foods (HMF, aw >= 0.85); and (3) the potential solutions
      to improve storage stability of food protein hydrolysates. In addition, we note
      there is a great need for evaluation of biofunction availability of bioactive
      peptides in food protein hydrolysates during storage. 

PMID- 24915380
TI  - Wheat dough microstructure: the relation between visual structure and mechanical
      behavior.
AB  - The microstructure of food matrixes, and specifically that of wheat-flour dough,
      determines mechanical behavior. Consequently, the analysis of such microstructure
      is both necessary and useful for understanding the physico-chemical and
      mechanical alterations during the production of cereal-based products such as
      breads. Confocal laser scanning microscopy (CLSM) is an established tool for the
      investigation of these matrix properties due to its methodical advantages such as
      easy preparation and handling, and the high depth resolution due to the optical
      sectioning of probes. This review focuses on the microstructure of wheat-flour
      dough from a mechanical and visual point of view. It provides an overview of the
      dependencies between the visibly detectable microstructural elements achieved by
      CLSM and the physical determined rheological properties. Current findings in this
      field, especially on numerical microstructure features, are described and
      discussed, and possibilities for enhancing the analytical methodology are
      presented. 

PMID- 24915381
TI  - Effect of processing on phenolic antioxidants of fruits, vegetables, and grains-
      a review.
AB  - Understanding the influence of processing operations such as drying/dehydration,
      canning, extrusion, high hydrostatic pressure, pulsed electric field, and ohmic
      heating on the phytochemicals of fruits, vegetables, and grains is important in
      retaining the health benefiting properties of these antioxidative compounds in
      processed food products. Most of the previous investigations in the literature on
      the antioxidants of fruits, vegetables, and grains have shown that food
      processing operations reduced the antioxidants of the processed foods, which is
      also the usual consumer perception. However, in the last decade some articles in
      the literature reported that the evaluation of nutritional quality of processed
      fruits and vegetables not only depend on the quantity of vitamin C but should
      include analyses of other antioxidant phytochemicals and antioxidant activity.
      Thermal processing increased the total antioxidant activity of tomato and sweet
      corn. Most importantly, analysis also depends on the condition, type, and
      mechanism of antioxidant assays used. This review aims to provide concise
      information on the influence of various thermal and nonthermal food-processing
      operations on the stability and kinetics of health beneficial phenolic
      antioxidants of fruits, vegetables, and grains. 

PMID- 24915382
TI  - New perspectives on dietary-derived treatments and food safety-antinomy in a new
      era.
AB  - Despite the advances in science and technology and wide use of chemical drugs,
      dietary intervention (or food therapy) remains useful in preventing or treating
      many human diseases. A huge body of evidence shows that the dietary pattern or
      habit is also an important contributing factor to the development of chronic
      diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cancers. In
      recent years, over-the-counter health foods, nutraceuticals, and plant-derived
      medicinal products have been gaining popularity all over the world, particularly
      in developed countries. Unfortunately, owing to the contamination with various
      harmful substances in foods and the presence of toxic food components, food-borne
      diseases have also become increasingly problematic. Incidents of food poisonings
      or tainted food have been increasing worldwide, particularly in China and other
      developing countries. Therefore, the government should put in a greater effort in
      enforcing food safety by improving the surveillance mechanism and exerting
      highest standards of quality control for foods.

PMID- 24915383
TI  - Biochemical and functional properties of wheat gliadins: a review.
AB  - Gliadins account for 40-50% of the total storage proteins of wheat and are
      classified into four subcategories, alpha-, beta-, gamma-, and omega-gliadins.
      They have also been classified as omega5-, omega1, 2-, alpha/beta-, and gamma
      gliadins on the basis of their primary structure and molecular weight. Cysteine
      residues of gliadins mainly form intramolecular disulfide bonds, although alpha
      gliadins with odd numbers of cysteine residues have also been reported. Gliadins
      are generally regarded to possess globular protein structure, though recent
      studies report that the alpha/beta-gliadins have compact globular structures and
      gamma- and omega-gliadins have extended rod-like structures. Newer techniques
      such as Mass Spectrometry with the development of matrix-assisted laser
      desorption/ionization (MALDI) in combination with time-of-flight mass
      spectrometry (TOFMS) have been employed to determine the molecular weight of
      purified omega- gliadins and to carry out the direct analysis of bread and durum
      wheat gliadins. Few gliadin alleles and components, such as Gli-B1b, Gli-B2c and
      Gli-A2b in bread wheat cultivars, gamma-45 in pasta, gamma-gliadins in cookies,
      lower gliadin content for chapatti and alteration in Gli 2 loci in tortillas have
      been reported to improve the product quality, respectively. Further studies are
      needed in order to elucidate the precise role of gliadin subgroups in dough
      strength and product quality. 

PMID- 24915384
TI  - Flavonoids and immune function in human: a systematic review.
AB  - Flavonoids, through a modulation of immune function, have been suggested to be
      involved in the role played by plant foods in disease prevention. We performed a
      systematic search in the MEDLINE database to review the effect of flavonoid-rich
      foods and flavonoids supplements on immune function. A total of 58 studies, were
      identified as suitable: 41 addressed in vivo proinflammatory cytokines and 15
      measured ex vivo markers of immune function. According to our findings and on the
      basis of single food items, the number of studies in humans is limited and, for
      galenic supplements, only quercetin has been investigated. More evidences are
      needed to clarify the role of flavonoids as modulator of immune function in
      humans. 

PMID- 24915385
TI  - Comparison of molecular techniques with other methods for identification and
      enumeration of probiotics in fermented milk products.
AB  - Nowadays, an increasing attention is being given to fermented milk products
      including yogurt, kefir, buttermilk, and acidophilus milk. Fermented milks,
      especially the ones containing probiotics, are claimed to be useful for health of
      host (such as intestinal- and immune-associated diseases). Their healthful
      effects could be significantly enhanced by incorporating probiotic
      microorganisms; those have healthful advantages for host when consumed in an
      appropriate viable number in food products. Probiotic dairy products have stepped
      to the market and are being commercially produced under various brand names. In
      addition, these products are legislatively obliged to be labeled for the
      microorganisms contained. Therefore, identification and enumeration of their
      microorganisms are a cause of concern. Several culture-dependent methods have
      been introduced and used to identify the microorganisms, in which the researchers
      have experienced multiple difficulties. Thereby, molecular approaches were
      present as an alternative, offering advantages such as accuracy, sensitivity,
      specificity, and speed. This article reviews the molecular approaches employed
      for identification and enumeration of probiotics in fermented milk products. 

PMID- 24915386
TI  - Retention of provitamin a carotenoids in staple crops targeted for
      biofortification in Africa: cassava, maize and sweet potato.
AB  - HarvestPlus, part of the Consultative Group on Internation Agriculture research
      (CGIAR) Program on Agriculture for Nutrition and Health (A4NH) uses conventional
      plant breeding techniques to develop staple food crops that are rich in
      micronutrients, a food-based approach to reduce micronutrient malnutrition known
      as biofortification. The nutritional breeding targets are established based on
      the food intake of target populations, nutrient losses during storage and
      processing and bioavailability. This review collates the evidence on the
      retention of provitamin A carotenoid (pVAC) after processing, cooking, and
      storing of the staple crops targeted for pVAC biofortification: cassava, maize,
      and sweet potato. Sun drying was more detrimental to the pVAC levels (27-56%
      retention) in cassava than shade (59%) or oven (55-91%) drying, while the pVAC
      retention levels (66-96%) in sweet potato were not significantly different among
      the various drying methods. Overall, boiling and steaming had higher pVAC
      retention (80-98%) compared to baking (30-70%) and frying (18-54%). Gari, the
      most frequently consumed form of cassava in West Africa had the lowest pVAC
      retention (10-30%). The pVAC retention of maize grain and cassava and sweet
      potato flour reached levels as low as 20% after 1-4 months of storage and was
      highly dependent on genotype. Therefore, we recommend that an evaluation of the
      pVAC degradation rate among different genotypes be performed before a high pVAC
      crop is promoted. 

PMID- 24915387
TI  - Isolation and analysis of bioactive compounds in Capsicum peppers.
AB  - An overview of the state of the art in the extraction, isolation, and analytical
      determination of bioactive compounds in peppers of the genus Capsicum is
      presented. The review is structured by classes of phytochemicals. Both major and
      minor constituents of peppers are considered. Modern trends in analytical
      chemistry of nutrients in regard to pepper analysis with particular focus on
      chromatographic and related methods are discussed. Attention was paid to
      controversial questions of pepper analysis, including but not limited to problems
      of sample degradation and the completeness of extraction of target analytes. The
      rationale for choosing an optimal strategy of analysis is given. 

PMID- 24915388
TI  - Protein-energy malnutrition: a risk factor for various ailments.
AB  - The wheel of industrialization that spun throughout the last century resulted in
      urbanization coupled with modifications in lifestyles and dietary habits.
      However, the communities living in developing economies are facing many problems
      related to their diet and health. Amongst, the prevalence of nutritional problems
      especially protein-energy malnutrition (PEM) and micronutrients deficiencies are
      the rising issues. Moreover, the immunity or susceptibility to infect-parasitic
      diseases is also directly linked with the nutritional status of the host.
      Likewise, disease-related malnutrition that includes an inflammatory component is
      commonly observed in clinical practice thus affecting the quality of life. The
      PEM is treatable but early detection is a key for its appropriate management.
      However, controlling the menace of PEM requires an aggressive partnership between
      the physician and the dietitian. This review mainly attempts to describe the
      pathophysiology, prevalence and consequences of PEM and aims to highlight the
      importance of this clinical syndrome and the recent growth in our understanding
      of the processes behind its development. Some management strategies/remedies to
      overcome PEM are also the limelight of the article. In the nutshell, early
      recognition, prompt management, and robust follow up are critical for best
      outcomes in preventing and treating PEM. 

PMID- 24915389
TI  - The growing role of front-of-pack nutrition profile labeling: a consumer
      perspective on key issues and controversies.
AB  - Nutrition-related diseases, such as some cancers, heart diseases, and obesity,
      belong to the most challenging health concerns of our time. Communicating
      intuitive and simple nutrition information by means of front-of-pack (FOP)
      nutrition profile signpost labeling is increasingly seen as an essential tool in
      efforts to combat unhealthy food choices and improve public health. Consequently,
      much attention in policy and research is given to nutrient profiling methods and
      the determination of optimal nutrition criteria. Although consumer research on
      nutrition signpost labeling is now gradually appearing in the literature, the
      value and meaning of these labeling systems for consumers have received less
      attention. In the current debate a concise overview is lacking of the consumer
      perspective, including relevant psychological phenomena, in relation to much
      debated controversies surrounding these labels and their further development,
      such as the most effective type of signpost labeling system and varying
      stakeholder interests. Therefore, this paper aims to critically review the
      literature in the consumer domain of FOP nutrition labeling in order to
      illustrate the strengths and weaknesses of this form of nutrition education from
      a consumer perspective. 

PMID- 24915390
TI  - Therapeutic and nutraceutical potential of bioactive compounds extracted from
      fruit residues.
AB  - The growing interest in the substitution of synthetic food antioxidants by
      natural ones has fostered research in identifying new low-cost antioxidants
      having commercial potential. Fruits such as mango, banana, and those belonging to
      the citrus family leave behind a substantial amount of residues in the form of
      peels, pulp, seeds, and stones. Due to lack of infrastructure to handle a huge
      quantity of available biomass, lack of processing facilities, and high processing
      cost, these residues represent a major disposal problem, especially in developing
      countries. Because of the presence of phenolic compounds, which impart
      nutraceutical properties to fruit residues, such residues hold tremendous
      potential in food, pharmaceutical, and cosmetic industries. The biological
      properties such as anticarcinogenicity, antimutagenicity, antiallergenicity, and
      antiageing activity have been reported for both natural as well as synthetic
      antioxidants. Special attention is focused on extraction of bioactive compounds
      from inexpensive or residual sources. The purpose of this review is to
      characterize different phenolics present in the fruit residues, discuss the
      antioxidant potential of such residues and the assays used in determination of
      antioxidant properties, discuss various methods for efficient extraction of the
      bioactive compounds, and highlight the importance of fruit residues as potential
      nutraceutical resources and biopreservatives. 

PMID- 24915392
TI  - Enhancement of food processes by ultrasound: a review.
AB  - In food processing, the applications of ultrasound can be divided into two
      categories, namely replacing traditional technologies and assisting traditional
      technologies. In the latter case, the processing efficiency is enhanced and the
      disadvantageous of traditional technologies during processing are improved. These
      ultrasonic effects can be defined as ultrasonic enhancement of food processes.
      This review is focused on the use of ultrasound to enhance various food
      processes, including extraction, freezing, thawing, brining, oxidation,
      filtration, and drying/dehydration. The major functions of ultrasound in
      enhancing these processes and the factors which can affect the ultrasonic
      enhancement are elucidated. In the meantime, the strategies of modeling these
      processes enhanced by ultrasound are provided. Future studies should pay more
      attention to elucidate the ultrasonic effects during freezing, thawing, brining,
      oxidation, and filtration processes. Furthermore, when it comes to design the
      ultrasound equipment at the industrial level, it is better to quantify the
      ultrasonic effects through numerical stimulation. 

PMID- 24915393
TI  - Nondestructive spectroscopic and imaging techniques for quality evaluation and
      assessment of fish and fish products.
AB  - Nowadays, people have increasingly realized the importance of acquiring high
      quality and nutritional values of fish and fish products in their daily diet.
      Quality evaluation and assessment are always expected and conducted by using
      rapid and nondestructive methods in order to satisfy both producers and
      consumers. During the past two decades, spectroscopic and imaging techniques have
      been developed to nondestructively estimate and measure quality attributes of
      fish and fish products. Among these noninvasive methods, visible/near-infrared
      (VIS/NIR) spectroscopy, computer/machine vision, and hyperspectral imaging have
      been regarded as powerful and effective analytical tools for fish quality
      analysis and control. VIS/NIR spectroscopy has been widely applied to determine
      intrinsic quality characteristics of fish samples, such as moisture, protein,
      fat, and salt. Computer/machine vision on the other hand mainly focuses on the
      estimation of external features like color, weight, size, and surface defects.
      Recently, by incorporating both spectroscopy and imaging techniques in one
      system, hyperspectral imaging cannot only measure the contents of different
      quality attributes simultaneously, but also obtain the spatial distribution of
      such attributes when the quality of fish samples are evaluated and measured. This
      paper systematically reviews the research advances of these three nondestructive
      optical techniques in the application of fish quality evaluation and
      determination and discuss future trends in the developments of nondestructive
      technologies for further quality characterization in fish and fish products.

PMID- 24915391
TI  - Sugar-fat seesaw: a systematic review of the evidence.
AB  - Further to reports of a reciprocal relationship between sugar and fat intakes,
      this review aimed to provide an in-depth analysis and to determine the likely
      influence of this relationship on the achievement of population dietary
      guidelines. Using systematic methods, relevant literature was selected according
      to preset criteria. A strong and consistent inverse association was found between
      total sugars and total fat intakes expressed as percentage energy. Fewer studies
      considered absolute intakes and these reported a positive relationship, which may
      be influenced by confounding with energy intakes. Evidence for an inverse
      relationship between percentage energy from fat and extrinsic sugars was weaker
      and less consistent than for fat and total sugars. Reciprocal relationships were
      also observed for sugar-saturated fat, sugar-protein, sugar-alcohol, and sugar
      starch expressed as percentage energy. Under-reporting of dietary intakes had no
      major influence on the findings. This review confirms the existence of the sugar
      fat seesaw on a percentage energy basis and concludes that it is most likely
      explained by a combination of mathematical and food compositional effects. This
      finding is relevant because dietary guidelines are expressed as percentage energy
      and implies that at the population level multiple guidelines may be difficult to
      achieve in practice. 

PMID- 24915394
TI  - Recent advances in methods and techniques for freshness quality determination and
      evaluation of fish and fish fillets: a review.
AB  - The freshness quality of fish plays an important role in human health and the
      acceptance of consumers as well as in international fishery trade. Recently, with
      food safety becoming a critical issue of great concern in the world,
      determination and evaluation of fish freshness is much more significant in
      research and development. This review renovates and concentrates recent advances
      of evaluating methods for fish freshness as affected by preharvest and
      postharvest factors and highlights the determination methods for fish freshness
      including sensory evaluation, microbial inspection, chemical measurements of
      moisture content, volatile compounds, protein changes, lipid oxidation, and
      adenosine triphosphate (ATP) decomposition (K value), physical measurements, and
      foreign material contamination detection. Moreover, the advantages and
      disadvantages of these methods and techniques are compared and discussed and some
      viewpoints about the current work and future trends are also presented. 

PMID- 24915395
TI  - Recent developments and applications of hyperspectral imaging for quality
      evaluation of agricultural products: a review.
AB  - Food quality and safety is the foremost issue for consumers, retailers as well as
      regulatory authorities. Most quality parameters are assessed by traditional
      methods, which are time consuming, laborious, and associated with inconsistency
      and variability. Non-destructive methods have been developed to objectively
      measure quality attributes for various kinds of food. In recent years,
      hyperspectral imaging (HSI) has matured into one of the most powerful tools for
      quality evaluation of agricultural and food products. HSI allows characterization
      of a sample's chemical composition (spectroscopic component) and external
      features (imaging component) in each point of the image with full spectral
      information. In order to track the latest research developments of this
      technology, this paper gives a detailed overview of the theory and fundamentals
      behind this technology and discusses its applications in the field of quality
      evaluation of agricultural products. Additionally, future potentials of HSI are
      also reported. 

PMID- 24915396
TI  - Potential herbs and herbal nutraceuticals: food applications and their
      interactions with food components.
AB  - Since ancient times, herbs have been used as natural remedies for curing many
      physiological disorders. Traditional medicinal literature appreciated their value
      as nature's gift to mankind for the healing of illnesses. Some of the herbs have
      also been used for culinary purposes, and few of them have been used in cheese
      manufacture both as coagulating agents and flavor ingredients. Scientific
      investigations regarding biological activity and toxicity of chemical moieties
      present in many herbs have been carried out over a period of time. Consequently,
      literature related to the use of herbs or their functional ingredients in foods
      and their interaction with food constituents has been appearing in recent times.
      This article presents the information regarding some biologically active
      constituents occurring in commonly used herbs, viz., alkaloids, anthraquinones,
      bitters, flavonoids, saponins, tannins, and essential oils, their physiological
      functionalities, and also the description of few herbs of importance, viz.,
      Asparagus racemosus, Withania somnifera, Bacopa monniera, Pueraria tuberose,
      Emblica officinalis, Terminalia chebula, Terminalia belerica, Terminalia arjuna,
      and Aloe vera, in terms of their chemical composition, biological functionality,
      and toxicity. This article also reviews the use of herbs and their active
      ingredients in foods and their interactions with different food constituents. 

PMID- 24915397
TI  - Micronutrient and functional compounds biofortification of maize grains.
AB  - Maize, in addition to being the main staple food in many countries, is used in
      the production of hundreds of products. It is rich in compounds with potential
      benefits to health, such as carotenoids, phenolic compounds, vitamin E, and
      minerals that act as cofactors for antioxidant enzymes. Many of these compounds
      have been neglected thus far in the scientific literature. Nevertheless,
      deficiencies in the precursors of vitamin A and some minerals, such as iron and
      zinc, in maize, in association with the great genetic variability in its
      cultivars and our genomic, transcriptomic, and metabolomic knowledge of this
      species make targeted biofortification strategies for maize promising. This
      review discusses the potential of the main microconstituents found in maize with
      a focus on studies aimed at biofortification. 

PMID- 24915398
TI  - Novel trends to revolutionize preservation and packaging of fruits/fruit
      products: microbiological and nanotechnological perspectives.
AB  - Fruit preservation and packaging have been practiced since ages to maintain the
      constant supply of seasonal fruits over lengthened periods round the year.
      However, health and safety issues have attracted attention in recent decades. The
      safety and quality assurance of packaged fruits/fruit products are vital concerns
      in present day world-wide-integrated food supply chains. The growing demand of
      minimally or unprocessed packaged fruits has further aggravated the safety
      concerns which fuelled in extensive research with objectives to develop novel
      techniques of food processing, preservation, and packaging as well as for rapid,
      accurate, and early detection of contaminant products/microbes. Nevertheless,
      fruits and fruit-based products have yet to observe a panoramic introduction.
      Tropics and subtropics are the stellar producers of a variety of fruits; majority
      if not all is perishable and prone to postharvest decay. This evoked the
      opportunity to critically review the global scenario of emerging and novel
      techniques for fruit preservation and packaging, hence providing insight for
      their future implementation. This review would survey key nanotechnology
      innovations applied in preservation, packaging, safety, and storage of fruits and
      fruit-based products. The challenges and pros and cons of wider application of
      these innovative techniques, their commercial potential, and consumer
      acceptability have also been discussed. 

PMID- 24915399
TI  - Using sensory properties of food to trigger swallowing: a review.
AB  - The effect of food consistency on swallowing function has been widely studied,
      and it is well recognized that by delaying the flow of the food bolus, thickened
      liquids can help in the management of swallowing dysfunction. However, fewer
      studies have been carried out on the impact of food sensory properties and
      related liking on swallowing function. This paper reviews the role of taste,
      olfaction, and trigeminal perceptions on swallowing function and highlights the
      need for a deeper investigation of this aspect of patient diet modification. 

PMID- 24915401
TI  - Food safety challenges--a Pakistan's perspective.
AB  - Biological, chemical, and physical contamination of foods is a terrifying threat
      for the health and economic growth in developing societies. Rampantly available
      literature on foodborne illnesses especially diarrhea among children exclusively
      depicts the intensified disease burden associated with foodborne illness in the
      underdeveloped economies. Prevalence of many pathogens in several foods is
      commonplace in Pakistan. Precise estimates for foodborne illnesses in Pakistan
      are hard to make because of the absence of any monitoring, surveillance, and
      infection control. Poor processing and storage of milk, cereal grains, and nuts
      are a major cause of aflatoxin contamination and mold proliferation. Numerous
      studies manifest a multitude of foods to be contaminated with heavy metals.
      Escalating population growth limits the economic potential of the individual and
      the state through a tendency among the traders and manufacturers to intentionally
      debase food commodities offered for sale to make profit at the cost of their
      quality and safety. Therefore, a growing trend of adulteration in foods during
      the recent past, particularly adulteration of milk, poses a pressing challenge
      for the government. This review is a concerted attempt to elucidate the
      prevailing food safety scenario in Pakistan. Information derived from local and
      related international studies will be presented to clearly depict a picture of
      food safety in Pakistan. It is proposed that an extensive food safety
      infrastructure leading to a safer supply of foods needs to be devised, designed,
      and implemented. 

PMID- 24915400
TI  - Wine aroma compounds in grapes: a critical review.
AB  - Volatile organic compounds are vital to wine quality, determining their aroma and
      varietal characteristics. Which are present, and in what quantity, depends on the
      cultivar, the situation and soil of the vineyard, weather, cultivation methods,
      and wine-making practices. Here, we review the literature on the development of
      wine aroma compounds in grapes, and how it is affected by the above-named
      factors. Increasing understanding of these processes at the molecular level will
      aid vine growers in the optimal selection of harvest dates and other decisions
      favoring the consistent production of balanced, flavorful berries. 

PMID- 24915402
TI  - Inhibition of Angiotensin Converting Enzyme, Angiotensin II Receptor Blocking,
      and Blood Pressure Lowering Bioactivity across Plant Families.
AB  - Hypertension is a major risk factor for coronary heart disease, kidney disease,
      and stroke. Interest in medicinal or nutraceutical plant bioactives to reduce
      hypertension has increased dramatically. The main biological regulation of
      mammalian blood pressure is via the renin-angiotensin-aldosterone system. The key
      enzyme is angiotensin converting enzyme (ACE) that converts angiotensin I into
      the powerful vasoconstrictor, angiotensin II. Angiotensin II binds to its
      receptors (AT1) on smooth muscle cells of the arteriole vasculature causing
      vasoconstriction and elevation of blood pressure. This review focuses on the in
      vitro and in vivo reports of plant-derived extracts that inhibit ACE activity,
      block angiotensin II receptor binding and demonstrate hypotensive activity in
      animal or human studies. We describe 74 families of plants that exhibited
      significant ACE inhibitory activity and 16 plant families with potential AT1
      receptor blocking activity, according to in vitro studies. From 43 plant families
      including some of those with in vitro bioactivity, the extracts from 73 plant
      species lowered blood pressure in various normotensive or hypertensive in vivo
      models by the oral route. Of these, 19 species from 15 families lowered human BP
      when administered orally. Some of the active plant extracts, isolated bioactives
      and BP-lowering mechanisms are discussed. 

PMID- 24915403
TI  - Yacon (Smallanthus sonchifolius): a food with multiple functions.
AB  - Functional foods are the focus of many studies worldwide. This is justified by
      the effects they have on public health and thus interest in elucidation of the
      mechanisms involved in their actions. The present review aims to broaden the
      discussions of the functional properties attributed to yacon (Smallanthus
      sonchifolius), considered a food with multiple functions since it possesses
      bioactive compounds (antimicrobial, antioxidant, and probiotic substances) that
      exert beneficial effects on the body. Although some studies have already
      demonstrated several of these functions, clinical evidence is scarce, making it
      necessary that more studies are conducted in this area. Still, since the
      availability of this food in the market is relatively new, its popularity depends
      on publications aimed at consumer education and development of new products by
      the food industry. 

PMID- 24915404
TI  - Simple sequence repeat markers in genetic divergence and marker-assisted
      selection of rice cultivars: a review.
AB  - Sequencing of rice genome has facilitated the understanding of rice evolution and
      has been utilized extensively for mining of DNA markers to facilitate marker
      assisted breeding. Simple sequence repeat (SSR) markers that are tandemly
      repeated nucleotide sequence motifs flanked by unique sequences are presently the
      maker of choice in rice improvement due to their abundance, co-dominant
      inheritance, high levels of allelic diversity, and simple reproducible assay. The
      current level of genome coverage by SSR markers in rice is sufficient to employ
      them for genotype identification and marker-assisted selection in breeding for
      mapping of genes and quantitative trait loci analysis. This review provides
      comprehensive information on the mapping and applications of SSR markers in
      investigation of rice cultivars to study their genetic divergence and marker
      assisted selection of important agronomic traits. 

PMID- 24915405
TI  - Onion: nature protection against physiological threats.
AB  - Onion (Allium cepa L.) is found in various regions of Europe, North America,
      Asia, and Africa. It is one of the classic examples of Allium species used not
      only for culinary preparations but also for medicinal purposes. Onion with a
      variety of purposes is often used as a raw material in many dishes and accepts
      almost all of the traditions and culture. Owing to its storage characteristics
      and durability of shipping, onions have been traded more widely than most
      vegetables. The pungent fractions of garlic are mostly sulfur-containing moieties
      while its two chemical groups have marked effect on human health. These are
      flavonoids and ALK (EN)-based cysteine sulfoxides (ACSOs). Compounds in onions
      have been reported with a range of health benefits, including anticancer
      properties, antiplatelet activity, antithrombotic activity, antiasthmatic
      activity, and antibiotic effects. 

PMID- 24915406
TI  - Wheat-based traditional flat breads of India.
AB  - Wheat forms the basic ingredient for various bakery and traditional products.
      Wheat-based flat breads are one of the traditional products prepared in different
      parts of the world. Different regions of the world have inherited different
      preparation methods since time immemorial, which has led to the existence of
      traditional flat breads'. Being traditional, only a few have been extensively
      studied scientifically. India, being the second largest producer of wheat, has a
      great saga of traditional flat breads with different tastes and texture. This
      review is a compiled information related to the research studies carried out on
      some of the wheat-based traditional flat breads of India namely chapati, puri,
      tandoori roti, parantha (whole-wheat flour based) and parotta, naan, bhatura,
      kulcha (refined wheat flour based) which indicates the magnitude of attention
      they have drawn among the food scientists. The review delves upon the
      developments and improvements brought about in the storage stability and
      realization of large-scale production of few of these flat breads which has
      helped considerably to cater to the growing demand in the domestic as well as
      international markets. The review also indicates the possibility and the
      tremendous scope available for technological developments for traditional flat
      breads. 

PMID- 24915407
TI  - Effect of thermal treatment on meat proteins with special reference to
      heterocyclic aromatic amines (HAAs).
AB  - Meat is one of the most imperative protein sources available with respect to its
      production and consumption. It is the richest source of some valuable nutrients
      like proteins, essential amino acids, polyunsaturated fatty acids, vitamins, and
      minerals like iron, zinc, and selenium. Thermal treatment produces conformational
      changes in protein structure as well as flavor, texture, and appearance, and
      chemical properties of the ingredients are also changed. Heterocyclic aromatic
      amines (HAAs), potent mutagens/carcinogens, are formed during the cooking of meat
      at high temperature. The review paper highlights the effects of various cooking
      methods, i.e., pan-frying, deep-frying, charcoal grilling, and roasting, on the
      formation of HAAs. The levels of HAAs produced in cooked meats vary depending
      upon the cooking method, time of cooking, and the type of meat being cooked.
      Metabolic behavior of HAAs is very unique, they interfere in the activity of many
      enzymes, modify the metabolic pathways, and lead to the adduct formation of DNA.
      The application of black pepper and several other spices during processing may
      reduce the formation of these (HAAs) mutagenic compounds. 

PMID- 24915408
TI  - The Macrostructure of Milk Lipids: The Fat Globules.
AB  - The aim of this review article is to summarize the information available related
      to milk fat globules (MFGs) in order to highlight their contribution to the
      nutritional and technological characteristics of milk and dairy products. The
      macrostructure of milk lipids is composed of globules made up of triglycerides
      with different melting points, enveloped by a biological membrane from the
      mammary epithelial cell. In milks of different animal species, there are
      different-sized MFGs, ranging from diameters of less than 0.2 MUm to a maximum of
      15 MUm. The average diameter and the number of globules are affected by
      endogenous, physiological, and exogenous factors. The size of the globules in
      turn affects the qualitative characteristics of milk and cheese. In addition, the
      average diameter of the globules and their surface that is exposed to the
      digestive system affect fat digestibility in different ways. Finally, the
      components of the MFG membranes have been shown to take part in the secretion
      process of globules and to have a beneficial effect on human health. In
      conclusion, by acting on factors influencing the dimensions of the fat globules
      and by increasing the content of the milk membrane could help adapt milk
      production to specific consumer targets and improve milk nutritional properties. 

PMID- 24915411
TI  - The bioactivity and toxicological actions of carvacrol.
AB  - Carvacrol is a monoterpenic phenol produced by an abundant number of aromatic
      plants, including thyme and oregano. Presently, carvacrol is used in low
      concentrations as a food flavoring ingredient and preservative, as well as a
      fragrance ingredient in cosmetic formulations. In recent years, considerable
      research has been undertaken in an effort to establish the biological actions of
      carvacrol for its potential use in clinical applications. Results from in vitro
      and in vivo studies show that carvacrol possess a variety of biological and
      pharmacological properties including antioxidant, antibacterial, antifungal,
      anticancer, anti-inflammatory, hepatoprotective, spasmolytic, and vasorelaxant.
      The focus of this review is to evaluate the existing knowledge regarding the
      biological, pharmacological, and toxicological effects of carvacrol. 

PMID- 24915410
TI  - What makes good antioxidants in lipid-based systems? The next theories beyond the
      polar paradox.
AB  - The polar paradox states that polar antioxidants are more active in bulk lipids
      than their nonpolar counterparts, whereas nonpolar antioxidants are more
      effective in oil-in-water emulsion than their polar homologs. However, recent
      results, showing that not all antioxidants behave in a manner proposed by this
      hypothesis in oil and emulsion, lead us to revisit the polar paradox and to put
      forward new concepts, hypotheses, and theories. In bulk oil, new evidences have
      been brought to demonstrate that the crucial site of oxidation is not the air-oil
      interface, as postulated by the polar paradox, but association colloids formed
      with traces of water and surface active molecules such as phospholipids. The role
      of these association colloids on lipid oxidation and its inhibition by
      antioxidant is also addressed as well as the complex influence of the
      hydrophobicity on the ability of antioxidants to protect lipids from oxidation.
      In oil-in water emulsion, we have covered the recently discovered non linear (or
      cut-off) influence of the hydrophobicity on antioxidant capacity. For the first
      time, different mechanisms of action are formulated in details to try to account
      for this nonlinear effect. As suggested by the great amount of biological studies
      showing a cut-off effect, this phenomenon could be widespread in dispersed lipid
      systems including emulsions and liposomes as well as in living systems such as
      cultured cells. Works on the cut-off effect paves the way for the determination
      of the critical chain length which corresponds to the threshold beyond which
      antioxidant capacity suddenly collapses. The systematic search for this new
      physico-chemical parameter will allow designing novel phenolipids and other
      amphiphilic antioxidants in a rational fashion. Finally, in both bulk oils and
      emulsions, we feel that it is now time for a paradigm shift from the polar
      paradox to the next theories. 

PMID- 24915412
TI  - Quality-related enzymes in plant-based products: effects of novel food processing
      technologies part 2: pulsed electric field processing.
AB  - Pulsed electric field (PEF) processing is an effective technique for the
      preservation of pumpable food products as it inactivates vegetative microbial
      cells at ambient to moderate temperature without significantly affecting the
      nutritional and sensorial quality of the product. However, conflicting views are
      expressed about the effect of PEF on enzymes. In this review, which is part 2 of
      a series of reviews dealing with the effectiveness of novel food preservation
      technologies for controlling enzymes, the scientific literature over the last
      decade on the effect of PEF on plant enzymes is critically reviewed to shed more
      light on the issue. The existing evidence indicates that PEF can result in
      substantial inactivation of most enzymes, although a much more intense process is
      required compared to microbial inactivation. Depending on the processing
      condition and the origin of the enzyme, up to 97% inactivation of pectin
      methylesterase, polyphenol oxidase, and peroxidase as well as no inactivation
      have been reported following PEF treatment. Both electrochemical effects and
      Ohmic heating appear to contribute to the observed inactivation, although the
      relative contribution depends on a number of factors including the origin of the
      enzyme, the design of the PEF treatment chamber, the processing condition, and
      the composition of the medium. 

PMID- 24915409
TI  - Sex hormones and macronutrient metabolism.
AB  - The biological differences between males and females are determined by a
      different set of genes and by a different reactivity to environmental stimuli,
      including the diet, in general. These differences are further emphasized and
      driven by the exposure to a different hormone flux throughout the life. These
      differences have not been taken into appropriate consideration by the scientific
      community. Nutritional sciences are not immune from this "bias" and when
      nutritional needs are concerned, females are considered only when pregnant,
      lactating or when their hormonal profile is returning back to "normal," i.e., to
      the male-like profile. The authors highlight some of the most evident differences
      in aspects of biology that are associated with nutrition. This review presents
      and describes available data addressing differences and similarities of the
      "reference man" vs. the "reference woman" in term of metabolic activity and
      nutritional needs. According to this assumption, available evidences of sex
      associated differences of specific biochemical pathways involved in substrate
      metabolism are reported and discussed. The modulation by sexual hormones
      affecting glucose, amino acid and protein metabolism and the metabolization of
      nutritional fats and the distribution of fat depots, is considered targeting a
      tentative starting up background for a gender concerned nutritional science. 

PMID- 24915413
TI  - New food safety law: effectiveness on the ground.
AB  - The demand for safety in the US food supply from production to consumption
      necessitates a scientific, risk-based strategy for the management of
      microbiological, chemical, and physical hazards in food. The key to successful
      management is an increase in systematic collaboration and communication and in
      enforceable procedures with all domestic and international stakeholders. The
      enactment of the Food Safety Modernization Act (FSMA) aims to prevent or reduce
      large-scale food-borne illness outbreaks through stricter facility registration
      and records standards, mandatory prevention-based controls, increased facility
      inspections in the United States and internationally, mandatory recall authority,
      import controls, and increased consumer communication. The bill provisions are
      expected to cost $1.4 billion over the next four years. Effective implementation
      of the FSMA's 50 rules, reports, studies, and guidance documents in addition to
      an increased inspection burden requires further funding appropriations.
      Additional full-time inspectors and unprecedented foreign compliance is necessary
      for the full and effective implementation of the FSMA. 

PMID- 24915414
TI  - Assessing herbal products with health claims.
AB  - Herbs, herbal extracts, or phytochemicals are broadly used as foods, drugs, and
      as traditional medicines. These are well regulated in Europe, with thorough
      controls on both safety and efficacy or validity of health claims. However, the
      distinction between medicines and foods with health claims is not always clear.
      In addition, there are several cases of herbal products that claim benefits that
      are not scientifically demonstrated. This review details the European Union (EU)
      legislative framework that regulates the approval and marketing of herbal
      products bearing health claims as well as the scientific evidence that is needed
      to support such claims. To illustrate the latter, we focus on phytoecdysteroid
      (PE)-containing preparations, generally sold to sportsmen and bodybuilders. We
      review the limited published scientific evidence that supports claims for these
      products in humans. In addition, we model the in silico binding between different
      PEs and human nuclear receptors and discuss the implications of these putative
      bindings in terms of the mechanism of action of this family of compounds. We call
      for additional research to validate the safety and health-promoting properties of
      PEs and other herbal compounds, for the benefit of all consumers.

PMID- 24915416
TI  - Arthropod abundance and diversity in transgenic Bt soybean.
AB  - Before the commercialization of any insect-resistant genetically modified crop,
      it must be subjected to a rigorous premarket risk assessment. Here, possible
      effects of growing of transgenic Cry1Ac soybean on arthropod communities under
      field conditions were assessed for 2 yr and quantified in terms of arthropod
      community indices including the Shannon-Weaver diversity index, richness index,
      and dominance index. Our results showed no significant differences of diversity,
      richness, or dominant indices for Bt soybean compared with the recipient
      cultivar, conventional soybean, or sprayed conventional soybean. Conventional
      soybean treatment with insecticide had an adverse effect on the arthropod
      community after spraying, but arthropod community diversity recovered quickly. Bt
      soybean had no negative effect on the dominant distribution of subcommunities,
      including sucking pests, other pests, predators, parasitoids, and others except
      for lepidopteran pests. The dominance distribution of lepidopteran pests
      decreased significantly in Bt soybean because of the significant decrease in the
      numbers of Spodoptera litura (F.) and Ascotis selenaria Schiffermuller et Denis
      compared with the recipient cultivar. Our results showed that there were no
      negative effects of Cry1Ac soybean on the arthropod community in soybean field
      plots in the short term. 

PMID- 24915415
TI  - Genome-wide sequencing and an open reading frame analysis of
      dichlorodiphenyltrichloroethane (DDT) susceptible (91-C) and resistant (91-R)
      Drosophila melanogaster laboratory populations.
AB  - The Drosophila melanogaster 91-R and 91-C strains are of common origin, however,
      91-R has been intensely selected for dichlorodiphenyltrichloroethane (DDT)
      resistance over six decades while 91-C has been maintained as the non-selected
      control strain. These fly strains represent a unique genetic resource to
      understand the accumulation and fixation of mutations under laboratory conditions
      over decades of pesticide selection. Considerable research has been done to
      investigate the differential expression of genes associated with the highly DDT
      resistant strain 91-R, however, with the advent of whole genome sequencing we can
      now begin to develop an in depth understanding of the genomic changes associated
      with this intense decades-long xenobiotic selection pressure. Here we present the
      first whole genome sequencing analysis of the 91-R and 91-C fly strains to
      identify genome-wide structural changes within the open reading frames. Between
      strain changes in allele frequencies revealed a higher percent of new alleles
      going to fixation for the 91-R strain, as compared to 91-C (P<0.0001). These
      results suggest that resistance to DDT in the 91-R laboratory strain could
      potentially be due primarily to new mutations, as well as being polygenic rather
      than the result of a few major mutations, two hypotheses that remain to be
      tested. 

PMID- 24915418
TI  - Comment on "analysis of longitudinal trials with protocol deviations: a framework
      for relevant, accessible assumptions, and inference via multiple imputation," by
      Carpenter, Roger, and Kenward.

PMID- 24915419
TI  - Qualitative process analysis and modelling of emergency care workflow and
      interface management: identification of critical process steps.
AB  - OBJECTIVES: Over the past few years, the number of patients attending emergency
      services has increased steadily. As a result, emergency departments (EDs)
      worldwide face frequent crowding, with the risk of reduced treatment quality and
      impaired patient outcome, patient and staff dissatisfaction and inefficient use
      of ED resources. A qualitative process analysis and process modelling was used as
      a method to detect critical process steps in the ED with respect to time and
      efficiency. METHODS: The analysis was carried out by independent external process
      experts. Over a period of 1 week, the complete treatment process of 25 patients
      was recorded. The monitoring of overall activities, decision points, causalities
      and interfaces was based on the treatment of 100 additional patients and on
      interviews with nurses and physicians. The project was closed with the
      identification of the three most critical process steps and modelling of the
      standard emergency care process in an event-process chain (EPC). RESULTS: The
      most time-crucial steps detected by the analysis were the process of developing a
      tentative diagnosis, including consultation and advice seeking by inexperienced
      physicians, the interface to imaging diagnostics and the search of hospital beds
      for inpatients. The results were visualized by standardized modelling of an event
      process chain (EPC). CONCLUSION: The process analysis helped to identify
      inefficient process steps in the ED. Modelling with EPC is a useful tool to
      visualize and to understand the complexity of the emergency medical care and to
      identify key performance indicators for effective quality management.

PMID- 24915417
TI  - In vitro analysis of human immunodeficiency virus particle dissociation: gag
      proteolytic processing influences dissociation kinetics.
AB  - Human immunodeficiency virus particles undergo a step of proteolytic maturation,
      in which the main structural polyprotein Gag is cleaved into its mature subunits
      matrix (MA), capsid (CA), nucleocapsid (NC) and p6. Gag proteolytic processing is
      accompanied by a dramatic structural rearrangement within the virion, which is
      necessary for virus infectivity and has been proposed to proceed through a
      sequence of dissociation and reformation of the capsid lattice. Morphological
      maturation appears to be tightly regulated, with sequential cleavage events and
      two small spacer peptides within Gag playing important roles by regulating the
      disassembly of the immature capsid layer and formation of the mature capsid
      lattice. In order to measure the influence of individual Gag domains on lattice
      stability, we established Forster's resonance energy transfer (FRET) reporter
      virions and employed rapid kinetic FRET and light scatter measurements. This
      approach allowed us to measure dissociation properties of HIV-1 particles
      assembled in eukaryotic cells containing Gag proteins in different states of
      proteolytic processing. While the complex dissociation behavior of the particles
      prevented an assignment of kinetic rate constants to individual dissociation
      steps, our analyses revealed characteristic differences in the dissociation
      properties of the MA layer dependent on the presence of additional domains. The
      most striking effect observed here was a pronounced stabilization of the MA-CA
      layer mediated by the presence of the 14 amino acid long spacer peptide SP1 at
      the CA C-terminus, underlining the crucial role of this peptide for the
      resolution of the immature particle architecture. 

PMID- 24915420
TI  - Coordinate regulation between the nuclear receptor peroxisome proliferator
      activated receptor-gamma and cyclooxygenase-2 in renal epithelial cells.
AB  - The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent
      transcription factors involved in lipid metabolism and glucose utilization, in
      cell growth, differentiation and apoptosis, and in the regulation of pro
      inflammatory genes expression such as cyclooxygenase-2 (COX-2). PPARgamma is the
      main isoform in the renal inner medulla where it is believed to possess
      nephroprotective actions. In this kidney zone, COX-2 acts as an osmoprotective
      gene and its expression is modulated by changes in interstitial osmolarity. In
      the present work we evaluated whether hyperosmolar-induced COX-2 expression is
      modulated by PPARgamma in renal epithelial cells MDCK subjected to high NaCl
      medium. The results presented herein show that ligand-activated PPARgamma
      repressed COX-2 expression. But more important, the present findings show that
      hyperosmolar medium decreased PPARgamma protein and increases the PPARgamma
      phosphorylated form, which is inactive. ERK1/2 and p38 activation precedes
      PPARgamma disappearance and induced-COX-2 expression. Therefore, the decrease in
      PPARgamma expression is required for hyperosmotic induction of COX-2. We also
      found that PGE2, the main product of COX-2 in MDCK cells, induced these changes
      in PPARgamma protein. Our results may alert on the long term use of
      thiazolidinediones (TZD) since they could affect renal medullary function that
      depends on COX-2 for cellular protection against osmotic stress. 

PMID- 24915422
TI  - Integration of prevention of mother-to-child transmission of HIV (PMTCT)
      postpartum services with other HIV care and treatment services within the
      maternal and child health setting in Zimbabwe, 2012.
AB  - BACKGROUND: We assessed the integration of PMTCT services during the postpartum
      period including early infant diagnosis of HIV (EID) and adult and pediatric
      antiretroviral therapy (ART) in maternal and child health (MCH) facilities in
      Zimbabwe. METHODS AND FINDINGS: From August to December 2012 we conducted a cross
      sectional survey of a nationally representative sample of 151 MCH facilities. A
      questionnaire was used to survey each site about staff training, dried blood spot
      sample (DBS) collection, turnaround time (TAT) for test results, PMTCT services,
      and HIV care and treatment linkages for HIV-infected mothers and children and HIV
      exposed infants. Descriptive analyses were used. Of the facilities surveyed, all
      facilities were trained on DBS collection and 92% responded. Approximately, 99%
      of responding facilities reported providing DBS collection and a basic HIV
      exposed infant service package including EID, extended nevirapine prophylaxis,
      and use of cotrimoxazole. DBS collection was integrated with immunisations at 83%
      of facilities, CD4 testing with point-of-care machines was available at 37% of
      facilities, and ART for both mothers and children was provided at 27% of
      facilities. More than 80% of facilities reported that DBS test results take >4
      weeks to return; TAT did not have a direct association with any specific type of
      transport, distance to the lab, or intermediate stops for data to travel.
      CONCLUSIONS: Zimbabwe has successfully scaled up and integrated the national EID
      and PMTCT programs into the existing MCH setting. The long TAT of infant DBS test
      results and the lack of integrated ART programs in the MCH setting could reduce
      effectiveness of the national PMTCT and ART programs. Addressing these important
      gaps will support successful implementation of the 2014 Zimbabwe's PMTCT
      guidelines under which all HIV-infected pregnant and breastfeeding women will be
      offered life-long ART and decentralized ART care.

PMID- 24915421
TI  - A novel small molecule hybrid of vorinostat and DACA displays anticancer activity
      against human hormone-refractory metastatic prostate cancer through dual
      inhibition of histone deacetylase and topoisomerase I.
AB  - Vorinostat, which is an extensively studied inhibitor against histone deacetylase
      (HDAC), shows limited clinical activity to solid tumors. WJ35435, a new hybrid of
      vorinostat and DACA (a topoisomerase inhibitor) potently inhibited HDAC activity
      (in particular HDAC1 and HDAC6) in kinase assay and cell-based examination. The
      anti-HDAC effect was confirmed by the induction of histone H3 acetylation and
      phosphorylation, alpha-tubulin acetylation and gamma-H2AX formation. WJ35435
      showed better potency than vorinostat and DACA against PC-3 and DU-145, two human
      hormone-refractory metastatic prostate cancer (HRMPC) cell lines, but not benign
      prostate cells. WJ35435 at differential concentrations induced G1- or G2-phase
      arrest of the cell cycle in HRMPCs but not in benign prostate cells. WJ35435
      induced the formation of topoisomerase I-DNA cleavable complexes but not type
      IIalpha or -IIbeta. Topoisomerase activity assay confirmed the selective
      inhibition of topoisomerase I. WJ35435 induced profound DNA damage using comet
      tailing assay. WJ35435 was less effective than camptothecin and etoposide in
      inducing the phosphorylation and activation of Chk1, Chk2 and RPA32 which were
      crucial coordinators in DNA repair pathway, indicating a low DNA repair activity
      to WJ35435 action. Furthermore, WJ35435 showed an in vivo antitumor activity. A
      synergistic apoptosis (combination index=0.55) was obtained in combination
      between WJ35435 and MG-132 (a proteasome inhibitor). In summary, WJ35435 is a
      dual-targeted anticancer hybrid induces anti-HDAC and anti-topoisomerase I
      activities that cause DNA damage associated with a low DNA repair capability, and
      induce cell cycle arrest at G1- and G2-phase. Ultimately, WJ35435 inhibits cell
      proliferation and induces apoptosis of HRMPCs.

PMID- 24915424
TI  - An efficient synthesis of methyl 2-cyano-3,12-dioxoursol-1,9-dien-28-oate (CDDU
      methyl ester): analogues, biological activities, and comparison with oleanolic
      acid derivatives.
AB  - An efficient synthesis of methyl 2-cyano-3,12-dioxoursol-1,9-dien-28-oate (CDDU
      methyl ester) from commercially available ursolic acid, which features an
      oxidative ozonolysis-mediated C-ring enone formation, and provides the first
      access to ursolic acid-derived cyano enone analogues with C-ring activation.
      These new ursolic acid analogues show potent biological activities, with potency
      of approximately five-fold less than the corresponding oleanolic acid
      derivatives. 

PMID- 24915423
TI  - Discrete levels of Twist activity are required to direct distinct cell functions
      during gastrulation and somatic myogenesis.
AB  - Twist (Twi), a conserved basic helix-loop-helix transcriptional regulator,
      directs the epithelial-to-mesenchymal transition (EMT), and regulates changes in
      cell fate, cell polarity, cell division and cell migration in organisms from
      flies to humans. Analogous to its role in EMT, Twist has been implicated in
      metastasis in numerous cancer types, including breast, pancreatic and prostate.
      In the Drosophila embryo, Twist is essential for discrete events in gastrulation
      and mesodermal patterning. In this study, we derive a twi allelic series by
      examining the various cellular events required for gastrulation in Drosophila. By
      genetically manipulating the levels of Twi activity during gastrulation, we find
      that coordination of cell division is the most sensitive cellular event, whereas
      changes in cell shape are the least sensitive. Strikingly, we show that by
      increasing levels of Snail expression in a severe twi hypomorphic allelic
      background, but not a twi null background, we can reconstitute gastrulation and
      produce viable adult flies. Our results demonstrate that the level of Twi
      activity determines whether the cellular events of ventral furrow formation, EMT,
      cell division and mesodermal migration occur. 

PMID- 24915425
TI  - Stratification of carbon fractions and carbon management index in deep soil
      affected by the Grain-to-Green Program in China.
AB  - Conversion of slope cropland to perennial vegetation has a significant impact on
      soil organic carbon (SOC) stock in A horizon. However, the impact on SOC and its
      fraction stratification is still poorly understood in deep soil in Loess Hilly
      Region (LHR) of China. Samples were collected from three typical conversion
      lands, Robinia psendoacacia (RP), Caragana Korshinskii Kom (CK), and abandoned
      land (AB), which have been converted from slope croplands (SC) for 30 years in
      LHR. Contents of SOC, total nitrogen (TN), particulate organic carbon (POC), and
      labile organic carbon (LOC), and their stratification ratios (SR) and carbon
      management indexes (CMI) were determined on soil profiles from 0 to 200 cm.
      Results showed that the SOC, TN, POC and LOC stocks of RP were significantly
      higher than that of SC in soil layers of 0-10, 10-40, 40-100 and 100-200 cm
      (P<0.05). Soil layer of 100-200 cm accounted for 27.38-36.62%, 25.10-32.91%,
      21.59-31.69% and 21.08-26.83% to SOC, TN, POC and LOC stocks in lands of RP, CK
      and AB. SR values were >2.0 in most cases of RP, CK and AB. Moreover, CMI values
      of RP, CK, and AB increased by 11.61-61.53% in soil layer of 100-200 cm compared
      with SC. Significant positive correlations between SOC stocks and CMI or SR
      values of both surface soil and deep soil layers indicated that they were
      suitable indicators for soil quality and carbon changes evaluation. The Grain-to
      Green Program (GTGP) had strong influence on improving quantity and activity of
      SOC pool through all soil layers of converted lands, and deep soil organic carbon
      should be considered in C cycle induced by GTGP. It was concluded that converting
      slope croplands to RP forestlands was the most efficient way for sequestering C
      in LHR soils. 

PMID- 24915426
TI  - Agroecological factors correlated to soil DNA concentrations of Rhizoctonia in
      dryland wheat production zones of Washington state, USA.
AB  - The necrotrophic soilborne fungal pathogens Rhizoctonia solani AG8 and R. oryzae
      are principal causal agents of Rhizoctonia root rot and bare patch of wheat in
      dryland cropping systems of the Pacific Northwest. A 3-year survey of 33 parcels
      at 11 growers' sites and 60 trial plots at 12 Washington State University cereal
      variety test locations was undertaken to understand the distribution of these
      pathogens. Pathogen DNA concentrations in soils, quantified using real-time
      polymerase chain reaction, were correlated with precipitation, temperature maxima
      and minima, and soil texture factors in a pathogen-specific manner. Specifically,
      R. solani AG8 DNA concentration was negatively correlated with precipitation and
      not correlated with temperature minima, whereas R. oryzae concentration was
      correlated with temperature minima but not with precipitation. However, both
      pathogens were more abundant in soils with higher sand and lower clay content.
      Principal component analysis also indicated that unique groups of meteorological
      and soil factors were associated with each pathogen. Furthermore, tillage did not
      affect R. oryzae but affected R. solani AG8 at P = 0.06. Lower soil
      concentrations of R. solani AG8 but not R. oryzae occurred when the previously
      planted crop was a broadleaf (P < 0.05). Our findings showed that R. solani AG8
      concentrations were consistent with the general distribution of bare patch
      symptoms, based on field observations and surveys of other pathogens, but was
      present at many sites in which bare patch symptoms were not evident. Management
      of Rhizoctonia root rot and bare patch should account for the likelihood that
      each pathogen is affected by a unique group of agroecological variables.

PMID- 24915427
TI  - Geographic distribution of cryptic species of Plasmopara viticola causing downy
      mildew on wild and cultivated grape in eastern North America.
AB  - The putative center of origin of Plasmopara viticola, the causal agent of grape
      downy mildew, is eastern North America, where it has been described on several
      members of the family Vitaceae (e.g., Vitis spp., Parthenocissus spp., and
      Ampelopsis spp.). We have completed the first large-scale sampling of P. viticola
      isolates across a range of wild and cultivated host species distributed
      throughout the above region. Sequencing results of four partial genes indicated
      the presence of a new P. viticola species on Vitis vulpina in Virginia, adding to
      the four cryptic species of P. viticola recently recorded. The phylogenetic
      analysis also indicated that the P. viticola species found on Parthenocissus
      quinquefolia in North America is identical to Plasmopara muralis in Europe. The
      geographic distribution and host range of five pathogen species was determined
      through analysis of the internal transcribed spacer polymorphism of 896 isolates
      of P. viticola. Among three P. viticola species found on cultivated grape, one
      was restricted to Vitis interspecific hybrids within the northern part of eastern
      North America. A second species was recovered from V. vinifera and V. labrusca,
      and was distributed across most of the sampled region. A third species, although
      less abundant, was distributed across a larger geographical range, including the
      southern part of eastern North America. P. viticola clade aestivalis predominated
      (83% of isolates) in vineyards of the European winegrape V. vinifera within the
      sampled area, indicating that a single pathogen species may represent the primary
      threat to the European host species within eastern North America.

PMID- 24915428
TI  - Development of a multiplex assay for genus- and species-specific detection of
      Phytophthora based on differences in mitochondrial gene order.
AB  - A molecular diagnostic assay for Phytophthora spp. that is specific, sensitive,
      has both genus- and species-specific detection capabilities multiplexed, and can
      be used to systematically develop markers for detection of a wide range of
      species would facilitate research and regulatory efforts. To address this need, a
      marker system was developed based on the high copy sequences of the mitochondrial
      DNA utilizing gene orders that were highly conserved in the genus Phytophthora
      but different in the related genus Pythium and plants to reduce the importance of
      highly controlled annealing temperatures for specificity. An amplification primer
      pair designed from conserved regions of the atp9 and nad9 genes produced an
      amplicon of ~340 bp specific for the Phytophthora spp. tested. The TaqMan probe
      for the genus-specific Phytophthora test was designed from a conserved portion of
      the atp9 gene whereas variable intergenic spacer sequences were used for
      designing the species-specific TaqMan probes. Specific probes were developed for
      13 species and the P. citricola species complex. In silico analysis suggests that
      species-specific probes could be developed for at least 70 additional described
      and provisional species; the use of locked nucleic acids in TaqMan probes should
      expand this list. A second locus spanning three tRNAs (trnM-trnP-trnM) was also
      evaluated for genus-specific detection capabilities. At 206 bp, it was not as
      useful for systematic development of a broad range of species-specific probes as
      the larger 340-bp amplicon. All markers were validated against a test panel that
      included 87 Phytophthora spp., 14 provisional Phytophthora spp., 29 Pythium spp.,
      1 Phytopythium sp., and 39 plant species. Species-specific probes were validated
      further against a range of geographically diverse isolates to ensure uniformity
      of detection at an intraspecific level, as well as with other species having high
      levels of sequence similarity to ensure specificity. Both diagnostic assays were
      also validated against 130 environmental samples from a range of hosts. The only
      limitation observed was that primers for the 340 bp atp9-nad9 locus did not
      amplify Phytophthora bisheria or P. frigida. The identification of species
      present in a sample can be determined without the need for culturing by
      sequencing the genus-specific amplicon and comparing that with a reference
      sequence database of known Phytophthora spp.

PMID- 24915429
TI  - Discrimination of plant-parasitic nematodes from complex soil communities using
      ecometagenetics.
AB  - Many plant pathogens are microscopic, cryptic, and difficult to diagnose. The new
      approach of ecometagenetics, involving ultrasequencing, bioinformatics, and
      biostatistics, has the potential to improve diagnoses of plant pathogens such as
      nematodes from the complex mixtures found in many agricultural and biosecurity
      situations. We tested this approach on a gradient of complexity ranging from a
      few individuals from a few species of known nematode pathogens in a relatively
      defined substrate to a complex and poorly known suite of nematode pathogens in a
      complex forest soil, including its associated biota of unknown protists, fungi,
      and other microscopic eukaryotes. We added three known but contrasting species
      (Pratylenchus neglectus, the closely related P. thornei, and Heterodera avenae)
      to half the set of substrates, leaving the other half without them. We then
      tested whether all nematode pathogens-known and unknown, indigenous, and
      experimentally added-were detected consistently present or absent. We always
      detected the Pratylenchus spp. correctly and with the number of sequence reads
      proportional to the numbers added. However, a single cyst of H. avenae was only
      identified approximately half the time it was present. Other plant-parasitic
      nematodes and nematodes from other trophic groups were detected well but other
      eukaryotes were detected less consistently. DNA sampling errors or informatic
      errors or both were involved in misidentification of H. avenae; however, the
      proportions of each varied in the different bioinformatic pipelines and with
      different parameters used. To a large extent, false-positive and false-negative
      errors were complementary: pipelines and parameters with the highest false
      positive rates had the lowest false-negative rates and vice versa. Sources of
      error identified included assumptions in the bioinformatic pipelines, slight
      differences in primer regions, the number of sequence reads regarded as the
      minimum threshold for inclusion in analysis, and inaccessible DNA in resistant
      life stages. Identification of the sources of error allows us to suggest ways to
      improve identification using ecometagenetics.

PMID- 24915430
TI  - Recombinants of bean common mosaic virus (BCMV) and genetic determinants of BCMV
      involved in overcoming resistance in common bean.
AB  - Bean common mosaic virus (BCMV) exists as a complex of strains classified by
      reactions to resistance genes found in common bean (Phaseolus vulgaris); seven
      BCMV pathotypes have been distinguished thus far, numbered I to VII. Virus
      genetic determinants involved in pathogenicity interactions with resistance genes
      have not yet been identified. Here, we describe the characterization of two novel
      field isolates of BCMV that helped to narrow down these genetic determinants
      interacting with specific P. vulgaris resistance factors. Based on a biological
      characterization on common bean differentials, both isolates were classified as
      belonging to pathotype VII, similar to control isolate US10, and both isolates
      exhibited the B serotype. The whole genome was sequenced for both isolates and
      found to be 98 to 99% identical to the BCMV isolate RU1 (pathotype VI), and a
      single name was retained: BCMV RU1-OR. To identify a genetic determinant of BCMV
      linked to the BCMV pathotype VII, the whole genome was also sequenced for two
      control isolates, US10 and RU1-P. Inspection of the nucleotide sequences for BCMV
      RU1-OR and US10 (both pathotype VII) and three closely related sequences of BCMV
      (RU1-P, RU1-D, and RU1-W, all pathotype VI) revealed that RU1-OR originated
      through a series of recombination events between US10 and an as-yet-unidentified
      BCMV parental genome, resulting in changes in virus pathology. The data obtained
      suggest that a fragment of the RU1-OR genome between positions 723 and 1,961
      nucleotides that is common to US10 and RU1-OR in the P1-HC-Pro region of the BCMV
      genome may be responsible for the ability to overcome resistance in bean
      conferred by the bc-2(2) gene. This is the first report of a virus genetic
      determinant responsible for overcoming a specific BCMV resistance gene in common
      bean.

PMID- 24915431
TI  - Synergism between southern rice black-streaked dwarf virus and rice ragged stunt
      virus enhances their insect vector acquisition.
AB  - Southern rice black-streaked dwarf virus (SRBSDV), a tentative species in the
      genus Fijivirus, family Reoviridae, is a novel rice virus transmitted by the
      white-backed planthopper (Sogatella furcifera). Since its discovery in 2001,
      SRBSDV has spread rapidly throughout eastern and southeastern Asia and caused
      large rice losses in China and Vietnam. Rice ragged stunt virus (RRSV) (genus
      Oryzavirus, family Reoviridae) is a common rice virus vectored by the brown
      planthopper (Nilaparvata lugens). RRSV is also widely distributed in eastern and
      southeastern Asia but has not previously caused serious problems in China owing
      to its low incidence. With SRBSDV's spread, however, RRSV has become increasingly
      common in China, and is frequently found in co-infection with SRBSDV. In this
      study, we show that SRBSDV and RRSV interact synergistically, the first example
      of synergism between plant viruses in the family Reoviridae. Rice plants co
      infected with both viruses displayed enhanced stunting, earlier symptoms, and
      higher virus titers compared with singly infected plants. Furthermore, white
      backed and brown planthoppers acquired SRBSDV and RRSV, respectively, from co
      infected plants at higher rates. We propose that increased RRSV incidence in
      Chinese fields is partly due to synergism between SRBSDV and RRSV.

PMID- 24915432
TI  - Incidence of hepatocellular carcinoma in Texas Latinos, 1995-2010: an update.
AB  - BACKGROUND: A previous study showed Hepatocellular Carcinoma (HCC) rates to be
      higher among Latinos in Texas and highest among South Texas Latinos compared to
      other non-Hispanic whites (NHW) and other Latinos in the United States (U.S.). We
      used more recent data to assess trends in HCC among Texas Latinos and to reassess
      the elevated HCC incidence rate in Texas Latinos. METHODS: We used data from the
      U.S. SEER Program and the Texas Cancer Registry to calculate annual and 3-year
      moving average age-specific and age-adjusted HCC incidence rates, annual percent
      changes (APCs), and their corresponding 95% confidence intervals for Latinos and
      NHW in the U.S., Texas and South Texas. RESULTS: Texas Latino male and female
      incidence rates were 3.1 and 4.0 times higher than their NHW counterparts in SEER
      regions. Latino males and females in South Texas had the highest rates of HCC
      incidence overall; rate ratios were 3.6 and 4.2 among South Texas Latino males
      and females compared to SEER NHW counterparts. There are statistically
      significant increases in HCC incidence rates in all groups (Texas and South Texas
      Latinos and NHW groups) and across all age groups. The elevated HCC rates in
      Texas Latinos are consistent over the 1995-2010 period. CONCLUSIONS: The
      incidence of HCC among Latinos in South Texas remains higher than elsewhere in
      the U.S. and warrants closer investigation of potential risk factors related to
      prevailing conditions unique to the population including higher obesity and
      diabetes rates, environmental, cultural and socioeconomic factors and possibly
      genetic predisposition.

PMID- 24915435
TI  - Mechanisms of linezolid resistance among coagulase-negative staphylococci
      determined by whole-genome sequencing.
AB  - Linezolid resistance is uncommon among staphylococci, but approximately 2% of
      clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit
      resistance to linezolid (MIC, >=8 ug/ml). We performed whole-genome sequencing
      (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28
      linezolid-resistant CoNS (21 Staphylococcus epidermidis isolates and 7
      Staphylococcus haemolyticus isolates) obtained from blood cultures at a large
      teaching health system in California between 2007 and 2012. The following well
      characterized mutations associated with linezolid resistance were identified in
      the 23S rRNA: G2576U, G2447U, and U2504A, along with the mutation C2534U.
      Mutations in the L3 and L4 riboproteins, at sites previously associated with
      linezolid resistance, were also identified in 20 isolates. The majority of
      isolates harbored more than one mutation in the 23S rRNA and L3 and L4 genes. In
      addition, the cfr methylase gene was found in almost half (48%) of S. epidermidis
      isolates. cfr had been only rarely identified in staphylococci in the United
      States prior to this study. Isolates of the same sequence type were identified
      with unique mutations associated with linezolid resistance, suggesting
      independent acquisition of linezolid resistance in each isolate. IMPORTANCE:
      Linezolid is one of a limited number of antimicrobials available to treat drug
      resistant Gram-positive bacteria, but resistance has begun to emerge. We
      evaluated the genomes of 28 linezolid-resistant staphylococci isolated from
      patients. Multiple mutations in the rRNA and associated proteins previously
      associated with linezolid resistance were found in the isolates investigated,
      underscoring the multifocal nature of resistance to linezolid in Staphylococcus.
      Importantly, almost half the S. epidermidis isolates studied harbored a plasmid
      borne cfr RNA methylase gene, suggesting that the incidence of cfr may be higher
      in the United States than previously documented. This finding has important
      implications for infection control practices in the United States. Further, cfr
      is commonly detected in bacteria isolated from livestock, where the use of
      phenicols, lincosamides, and pleuromutilins in veterinary medicine may provide
      selective pressure and lead to maintenance of this gene in animal bacteria.

PMID- 24915436
TI  - Altered neurochemical levels in the rat brain following chronic nicotine
      treatment.
AB  - Converging evidence shows that neurochemical systems are crucial mediators of
      nicotine dependence. Our present study evaluates the effect of 3-month chronic
      nicotine treatment on the levels of multiple quaternary ammonium compounds as
      well as glutamate and gamma aminobutyric acid in the rat prefrontal cortex,
      dorsal striatum and hypothalamus. We observed a marked decrease of acetylcholine
      levels in the dorsal striatum (22.88%, p<0.01), reflecting the impact of chronic
      nicotine in local interneuron circuits. We found decreases of carnitine in the
      dorsal striatum and prefrontal cortex (19.44%, p<0.01; 13.58%, p<0.01,
      respectively), but robust enhancements of carnitine in the hypothalamus (26.59%,
      p<0.01), which may reflect the alterations in food and water intake during
      chronic nicotine treatment. Finally, we identified an increase of prefrontal
      cortex glutamate levels (8.05%, p<0.05), supporting previous studies suggesting
      enhanced prefrontal activity during chronic drug use. Our study shows that
      quaternary ammonium compounds are regulated in a highly brain region specific
      manner during chronic nicotine treatment, and provides novel insights into
      neurochemical regulation during nicotine use. 

PMID- 24915434
TI  - Identification of a new Sprouty protein responsible for the inhibition of the
      Bombyx mori nucleopolyhedrovirus reproduction.
AB  - The rat sarcoma-extracellular signal regulated kinase mitogen-activated protein
      kinases pathway, one of the most ancient signaling pathways, is crucial for the
      defense against Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Sprouty
      (Spry) proteins can inhibit the activity of this pathway by receptor tyrosine
      kinases. We cloned and identified a new B. mori gene with a Spry domain similar
      to the Spry proteins of other organisms, such as fruitfly, mouse, human, chicken,
      Xenopus and zebrafish, and named it BmSpry. The gene expression analysis showed
      that BmSpry was transcribed in all of the examined tissues and in all
      developmental stages from embryo to adult. BmSpry also induced expression of
      BmNPV in the cells. Our results indicated: (1) the knock-down of BmSpry led to
      increased BmNPV replication and silkworm larvae mortality; (2) over-expression of
      BmSpry led to reduced BmNPV replication; and (3) BmSpry regulated the activation
      of ERK and inhibited BmNPV replication. These results showed that BmSpry plays a
      crucial role in the antiviral defense of the silkworm both in vitro and in vivo. 

PMID- 24915438
TI  - Inorganic/organic small molecular semiconductor self-assembly to functional core
      shell nanoarchitectures for ultrasensitive chemiresistors to aniline vapor.
AB  - We developed a new method combining the in situ liquid-solid phase reaction and
      self-assembly in solution to synthesize novel inorganic/organic small molecular
      semiconductor core-shell nanoparticles of ZnS/PTCDA (ZPNPs). This method is a one
      step process which can produce stoichiometric inorganic/organic core-shell
      nanoparticles and does not introduce any impurity. The film of ZPNPs exhibited an
      ultrasensitive detection of aniline vapor. The film of ZPNPs can highly
      selectively distinguish aniline vapor from many volatile organic compounds and
      water due to the strong synergistic interactions of pi-pi and hydrogen-bonds
      between electron donor (aniline) and acceptor (PTCDA) molecules, in which the
      detection limit was lowered to 100 ppb at room temperature. 

PMID- 24915439
TI  - Image quality and radiation dose of lower extremity CT angiography using 70 kVp,
      high pitch acquisition and sinogram-affirmed iterative reconstruction.
AB  - OBJECTIVES: The purpose of this study was to assess image quality and radiation
      dose of lower extremity CT angiography (CTA) with 70 kVp, high pitch acquisition
      and sinogram-affirmed iterative reconstruction (SAFIRE). METHODS: Lower extremity
      CTAs were performed on 44 patients: 22 patients were examined using protocol A
      (120 kVp, pitch of 0.85 and 120 ml of contrast agent on a first-generation dual
      source CT) (120 kVp group) and 22 patients were evaluated with protocol B (70
      kVp, pitch of 2.2 and 80 ml of contrast agent on a second-generation dual-source
      CT) (70 kVp group). Images from the 120 kVp group were reconstructed with
      filtered back projection (FBP) and images from the 70 kVp group with SAFIRE. The
      attenuation, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio
      (CNR) were calculated. Two radiologists subjectively assessed image quality of
      lower extremity arteries, plantar arterial enhancement and venous contamination
      of all patients. Radiation dose was compared between the two groups. RESULTS:
      Higher mean intravascular attenuation was obtained in the 70 kVp group (70 vs.
      120 kVp group, 555.4 +/- 83.4 HU vs. 300.9 +/- 81.4 HU, P<0.001), as well as
      image noise (20.0 +/- 2.8 HU vs. 17.5 +/- 3.2 HU, P = 0.010), SNR (32.0 +/- 7.0
      vs. 19.1 +/- 6.9, P<0.001) and CNR (28.1 +/- 6.6 vs 15.9 +/- 6.3, P<0.001). No
      difference in subjective image quality and plantar arterial enhancement was found
      between 120 kVp group and 70 kVp group (all P>0.05). The venous contamination
      score was 1.5 +/- 0.8 for 120 kVp group while no venous contamination was found
      in 70 kVp group. The inter-observer agreement was moderate to good for both
      groups (0.515~1, P<0.001). The effective dose was lower in 70 kVp group (0.3 +/-
      0.1 mSv) than in 120 kVp group (1.6 +/- 0.7 mSv)(P<0.001). CONCLUSIONS: Lower
      extremity CTA using 70 kVp, high pitch acquisition and SAFIRE, except increasing
      imaging noise, allows for lower radiation dose and contrast material volume
      without compromising image quality.

PMID- 24915437
TI  - Chemical identity of hypothalamic neurons engaged by leptin in reproductive
      control.
AB  - The adipocyte-derived hormone leptin plays a critical role as a metabolic cue for
      the reproductive system. Conditions of low leptin levels observed in negative
      energy balance and loss-of-function mutations of leptin or leptin receptor genes
      are characterized by decreased fertility. In recent years, advances have been
      made for identifying possible hypothalamic neurons relaying leptin's
      neuroendocrine control of reproductive function. Studies from different
      laboratories have demonstrated that leptin action in the hypothalamo-pituitary
      gonadal (HPG) axis is exerted via hypothalamic interneurons regulating
      gonadotropin-releasing hormone (GnRH) cells, oppose to direct action on GnRH
      neurons. Following this observation, studies focused on identifying leptin
      responsive interneurons. Using a Cre-loxP system to re-express or delete the
      leptin receptor long form (LepRb) from kisspeptin neurons, our laboratory found
      that leptin's action on kiss1 cells is neither required nor sufficient for
      leptin's role in reproductive function. Endogenous re-expression of LepRb
      however, in glutamatergic neurons of the ventral premammilary nucleus (PMV) or
      ablation of agouti-related protein (AgRP) neurons from leptin signaling-deficient
      mice are both sufficient to induce puberty and improve fertility. Recent studies
      have also shown that leptin action in first order GABAergic neurons is required
      for fertility. Together, these studies begin to delineate key neuronal
      populations involved in leptin's action in reproduction. In this review, we
      discuss recent advances made in the field and highlight the questions yet to be
      answered. 

PMID- 24915440
TI  - Enantioselective DNA condensation induced by heptameric lanthanum helical
      supramolecular enantiomers.
AB  - DNA condensation induced by a pair of heptameric La(III) helical enantiomers M
      [La7(S-L)6(CO3)(NO3)6(OCH3)(CH3OH)7].2CH3OH.5H2O and P-[La7(R
      L)6(CO3)(NO3)6(OCH3)(CH3OH)5(H2O)2].2CH3OH.4H2O (M-La and P-La, L=2-(2
      hydroxybenzylamino)-3-carbamoylpropanoic acid) has been investigated by UV/vis
      spectroscopy, fluorescence spectroscopy, CD spectroscopy, EMSA, RALS, DLS, and
      SEM. The enantiomers M-La and P-La could induce CT-DNA condensation at a low
      concentration as observed in UV/vis spectroscopy. DNA condensates possessed
      globular nanoparticles with nearly homogeneous sizes in solid state determined by
      SEM (ca. 250 nm for M-La and ca. 200 nm for P-La). The enantiomers bound to DNA
      through electrostatic attraction and hydrogen bond interactions in a major
      groove, and rapidly condensed free DNA into its compact state. DNA decompaction
      has been acquired by using EDTA as disassembly agent, and analyzed by UV/vis
      spectroscopy, CD spectroscopy and EMSA. Moreover, the enantiomers M-La and P-La
      displayed discernible discrimination in DNA interaction and DNA condensation, as
      well as DNA decondensation. Our study suggested that lanthanum(III) enantiomers M
      La and P-La were efficient DNA packaging agents with potential applications in
      gene delivery.

PMID- 24915441
TI  - Dietary inulin supplementation modifies significantly the liver transcriptomic
      profile of broiler chickens.
AB  - Inclusion of prebiotics in the diet is known to be advantageous, with positive
      influences both on health and growth. The current study investigated the
      differences in the hepatic transcriptome profiles between chickens supplemented
      with inulin (a storage carbohydrate found in many plants) and controls. Liver is
      a major metabolic organ and has been previously reported to be involved in the
      modification of the lipid metabolism in chickens fed with inulin. A nutrigenomic
      approach through the analysis of liver RNA hybridized to the Affymetrix GeneChip
      Chicken Genome Array identified 148 differentially expressed genes among both
      groups: 104 up-regulated (>= 1.4-fold) and 44 down-regulated (<= 0.6-fold).
      Quantitative real-time PCR analysis validated the microarray expression results
      for five out of seven genes tested. The functional annotation analyses revealed a
      number of genes, processes and pathways with putative involvement in chicken
      growth and performance, while reinforcing the immune status of animals, and
      fostering the production of long chain fatty acids in broilers supplemented with
      5 g of inulin kg(-1) diet. As far as we are aware, this is the first report of a
      microarray based gene expression study on the effect of dietary inulin
      supplementation, supporting further research on the use of this prebiotic on
      chicken diets as a useful alternative to antibiotics for improving performance
      and general immunity in poultry farming, along with a healthier meat lipid
      profile.

PMID- 24915442
TI  - Scanning electron microscopy of male terminalia and its application to species
      recognition and phylogenetic reconstruction in the Drosophila saltans group.
AB  - The Drosophila saltans group consists of five subgroups and 21 species, most of
      which have been identified only by morphological aspects of the male terminalia
      revealed by drawings using a camera lucida and a bright-field microscope.
      However, several species in the group, mainly those included in the saltans
      subgroup, are difficult to differentiate using only these characteristics. In
      this study, we used scanning electron microscopy (SEM) to analyze 19 structures
      of the male terminalia in 10 species from the five saltans subgroups. Among these
      structures, nine could be identified only through SEM analysis. We aimed to find
      other characteristics useful for morphological recognition of these species and
      to use these characteristics for phylogenetic reconstruction. These morphological
      differences enabled us to effectively distinguish among sibling species. These
      findings confirmed the monophyly of this group as previously determined in
      evolutionary studies based on other markers. The single most parsimonious tree
      (CI = 87 and RI = 90) indicated that the cordata subgroup is the most basal
      lineage and the saltans subgroup is the most apical lineage, as shown in earlier
      studies based on morphological data. However, our findings differed somewhat from
      these studies with respect to the phylogenetic relationships of species in the
      saltans group indicating that this group is still a puzzle that remains to be
      deciphered.

PMID- 24915443
TI  - Plantar pressure in diabetic peripheral neuropathy patients with active foot
      ulceration, previous ulceration and no history of ulceration: a meta-analysis of
      observational studies.
AB  - AIMS: Elevated dynamic plantar pressures are a consistent finding in diabetes
      patients with peripheral neuropathy with implications for plantar foot
      ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes
      patients that had peripheral neuropathy and those with neuropathy with active or
      previous foot ulcers. METHODS: Published articles were identified from Medline
      via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of
      Science via ISI Web of Knowledge bibliographic databases. Observational studies
      reporting barefoot dynamic plantar pressure in adults with diabetic peripheral
      neuropathy, where at least one group had a history of plantar foot ulcers were
      included. Interventional studies, shod plantar pressure studies and studies not
      published in English were excluded. Overall mean peak plantar pressure (MPP) and
      pressure time integral (PTI) were primary outcomes. The six secondary outcomes
      were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the
      meta-analysis was published with PROPSERO, (registration number CRD42013004310).
      RESULTS: Eight observational studies were included. Overall MPP and PTI were
      greater in diabetic peripheral neuropathy patients with foot ulceration compared
      to those without ulceration (standardised mean difference 0.551, 95% CI 0.290
      0.811, p<0.001; and 0.762, 95% CI 0.303-1.221, p = 0.001, respectively). Sub
      group analyses demonstrated no significant difference in MPP for those with
      neuropathy with active ulceration compared to those without ulcers. A significant
      difference in MPP was found for those with neuropathy with a past history of
      ulceration compared to those without ulcers; (0.467, 95% CI 0.181- 0.753, p =
      0.001). Statistical heterogeneity between studies was moderate. CONCLUSIONS:
      Plantar pressures appear to be significantly higher in patients with diabetic
      peripheral neuropathy with a history of foot ulceration compared to those with
      diabetic neuropathy without a history of ulceration. More homogenous data is
      needed to confirm these findings.

PMID- 24915445
TI  - Key applications of plant metabolic engineering.
AB  - Great strides have been made in plant metabolic engineering over the last two
      decades, with notable success stories including Golden rice. Here, we discuss the
      field's progress in addressing four long-standing challenges: creating plants
      that satisfy their own nitrogen requirement, so reducing or eliminating the need
      for nitrogen fertilizer; enhancing the nutrient content of crop plants;
      engineering biofuel feed stocks that harbor easy-to-access fermentable
      saccharides by incorporating self-destructing lignin; and increasing
      photosynthetic efficiency. We also look to the future at emerging areas of
      research in this field.

PMID- 24915449
TI  - A free radical cascade cyclization of isocyanides with simple alkanes and
      alcohols.
AB  - A copper-catalyzed free-radical cascade cyclization of isocyanides with simple
      alkanes and alcohols was developed, which allowed convenient access to various
      alkyl-substituted phenanthridines. 

PMID- 24915446
TI  - Multiple infections of rodents with zoonotic pathogens in Austria.
AB  - Rodents are important reservoirs for a large number of zoonotic pathogens. We
      examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent
      populations in Austria, including three different hantaviruses, lymphocytic
      choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp.,
      Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In
      2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus
      flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two
      rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen,
      kidney, liver, brain, and ear pinna skin were collected. We screened selected
      tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox
      viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T.
      gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira
      spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species.
      Serological investigations were performed for hantaviruses, lymphocytic
      choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava
      Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-,
      orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala
      hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by
      serological methods. In addition, multiple infections with up to three pathogens
      were shown in nine animals of three rodent species from different trapping sites.
      In conclusion, these results show that rodents in Austria may host multiple
      zoonotic pathogens. Our observation raises important questions regarding the
      interactions of different pathogens in the host, the countermeasures of the
      host's immune system, the impact of the host-pathogen interaction on the fitness
      of the host, and the spread of infectious agents among wild rodents and from
      those to other animals or humans.

PMID- 24915450
TI  - Multilevel spatial structure impacts on the pollination services of Comarum
      palustre (Rosaceae).
AB  - Habitat destruction and fragmentation accelerate pollinator decline, consequently
      disrupting ecosystem processes such as pollination. To date, the impacts of
      multilevel spatial structure on pollination services have rarely been addressed.
      We focused on the effects of population spatial structure on the pollination
      services of Comarum palustre at three levels (i.e. within-population, between
      populations and landscape). For three years, we investigated 14 Belgian
      populations, which differed in their within-population flower density, population
      surface, closure (i.e. proportion of the population edge that consisted of woody
      elements) and isolation (i.e. percentage of woody area cover within a 500 m
      radius from the population centre). We tested whether these spatial
      characteristics impact on pollinator abundance and visitation rate and thus,
      reproductive success of C. palustre. Insects were observed in 15 randomly-chosen
      plots in each population. We tested for pollen limitation with supplemental hand
      cross pollination. Bumble bees and solitary bees were the major pollinators
      through all populations. Within populations, plots with high flower densities
      attracted high numbers of bumble bees and other insects. High bumble bee and
      solitary bee abundance was observed in populations presenting high proportions of
      woody edges and in populations within landscapes presenting high proportions of
      woody areas. Seed set resulting from open pollination varied with bumble bee and
      solitary bee visitation rate, leading to increased pollen limitation when
      pollinators were scarce. Since the reproductive success depended on the
      visitation rate of the main pollinators, which depended on multilevel spatial
      structure, wetland management plans should pay special attention to favour a
      mosaic of biotopes, including nesting sites and food resources for insects. This
      study particularly supports the relevance of a mix wetlands and woody habitats to
      bees. 

PMID- 24915451
TI  - Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic
      disorders.
AB  - BACKGROUND: Long-acting depot injections of drugs such as flupenthixol decanoate
      are extensively used as a means of long-term maintenance treatment for
      schizophrenia. OBJECTIVES: To evaluate the effects of flupenthixol decanoate in
      comparison with placebo, oral antipsychotics and other depot neuroleptic
      preparations for people with schizophrenia and other severe mental illnesses, in
      terms of clinical, social and economic outcomes. SEARCH METHODS: We identified
      relevant trials by searching the Cochrane Schizophrenia Group Trials Register in
      March 2009 and then for this update version, a search was run in April 2013. The
      register is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO.
      References of all identified studies were inspected for further trials. We
      contacted relevant pharmaceutical companies, drug approval agencies and authors
      of trials for additional information. SELECTION CRITERIA: All randomised
      controlled trials that focused on people with schizophrenia or other similar
      psychotic disorders where flupenthixol decanoate had been compared with placebo
      or other antipsychotic drugs were included. All clinically relevant outcomes were
      sought. DATA COLLECTION AND ANALYSIS: Review authors independently selected
      studies, assessed trial quality and extracted data. For dichotomous data we
      estimated risk ratios (RR) with 95% confidence intervals (CI) using a fixed
      effect model. Analysis was by intention-to-treat. We summated normal continuous
      data using mean difference (MD), and 95% CIs using a fixed-effect model. We
      presented scale data only for those tools that had attained prespecified levels
      of quality. Using Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) we created 'Summary of findings tables and assessed risk of
      bias for included studies. MAIN RESULTS: The review currently includes 15
      randomised controlled trials with 626 participants. No trials compared
      flupenthixol decanoate with placebo.One small study compared flupenthixol
      decanoate with an oral antipsychotic (penfluridol). Only two outcomes were
      reported with this single study, and it demonstrated no clear differences between
      the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00,
      CI 0.33 to 27.23,very low quality evidence) and requiring anticholinergic
      medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality
      evidence).Ten studies in total compared flupenthixol decanoate with other depot
      preparations, though not all studies reported on all outcomes of interest. There
      were no significant differences between depots for outcomes such as relapse at
      medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence),
      and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to
      1.23, low quality evidence). There was no difference in numbers of participants
      leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76
      to 1.99, low quality evidence) nor with numbers of people requiring
      anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI
      0.75 to 2.25, low quality evidence).Three studies in total compared high doses
      (100 to 200 mg) of flupenthixol decanoate with the standard doses (~40mg) per
      injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI
      0.27 to 3.69, low quality evidence) to be similar between the groups. However
      people receiving a high dose had slightly more favourable medium term mental
      state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD 
      10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant
      difference in the use of anticholinergic medications to deal with side effects at
      short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence).
      One trial comparing a very low dose of flupenthixol decanoate (~6 mg) with a low
      dose (~9 mg) per injection reported no difference in relapse rates (n = 59, 1
      RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence). AUTHORS' CONCLUSIONS: In
      the current state of evidence, there is nothing to choose between flupenthixol
      decanoate and other depot antipsychotics. From the data reported in clinical
      trials, it would be understandable to offer standard dose rather than the high
      dose depot flupenthixol as there is no difference in relapse. However, data
      reported are of low or very low quality and this review highlights the need for
      large, well-designed and reported randomised clinical trials to address the
      effects of flupenthixol decanoate.

PMID- 24915452
TI  - The transferability of diatoms to clothing and the methods appropriate for their
      collection and analysis in forensic geoscience.
AB  - Forensic geoscience is concerned with the analysis of geological materials in
      order to compare and exclude environmental samples from a common source, or to
      identify an unknown provenance in a criminal investigation. Diatom analysis is
      currently an underused technique within the forensic geoscience approach, which
      has the potential to provide an independent ecological assessment of trace
      evidence. This study presents empirical data to provide a preliminary evidence
      base in order to be able to understand the nature of diatom transfers to items of
      clothing, and the collection of transferred diatom trace evidence from a range of
      environments under experimental conditions. Three diatom extraction methods were
      tested on clothing that had been in contact with soil and water sites: rinsing in
      water (RW), rinsing in ethanol (RE), and submersion in H2O2 solution (H).
      Scanning electron microscopy (S.E.M.) analysis was undertaken in order to examine
      the degree of diatom retention on treated clothing samples. The total diatom
      yield and species richness data was recorded from each experimental sample in
      order to compare the efficacy of each method in collecting a representative
      sample for analysis. Similarity was explored using correspondence analysis. The
      results highlight the efficiency of H2O2 submersion in consistently extracting
      high diatom counts with representative species from clothing exposed to both
      aquatic and terrestrial sites. This is corroborated by S.E.M. analysis. This
      paper provides an important empirical evidence base for both establishing that
      diatoms do indeed transfer to clothing under forensic conditions in a range of
      environments, and in identifying that H2O2 extraction is the most efficient
      technique for the optimal collection of comparative samples. There is therefore
      potentially great value in collecting and analysing diatom components of
      geoforensic samples in order to aid in forensic investigation. 

PMID- 24915453
TI  - Lethal hepatocellular necrosis associated with herbal polypharmacy in a patient
      with chronic hepatitis B infection.
AB  - Following a short treatment for irritable bowel with the following herbs:
      Astragalus propinquus, Codonopsis pilosula, Paeonia sp., Atractylodes
      macrocephala, Pueraria sp., Poria cocos, Dioscorea opposita, Patriniae, Psoralea
      corylifolia, Alpinia katsumadai, Glycyrrhiza uralensis and Dolomiaea souliei sp.
      a 43-year-old woman developed acute severe liver failure requiring liver
      transplantation. Histopathological examination of the liver showed massive
      hepatic necrosis in keeping with drug/chemical toxicity. Surgery was followed by
      multiorgan failure and death. While numerous studies have evaluated the effect of
      polypharmacy, the study of multiple concurrent herb use is only just emerging,
      despite the popularity of herbal medicine use in the western world. As this case
      demonstrates that fulminant hepatic failure and death may be caused by the
      concomitant use of a number of herbal products, the possibility of untoward
      effects from herbal polypharmacy must be increasingly considered in the
      evaluation of medicolegal cases. 

PMID- 24915454
TI  - The intestinal archaea Methanosphaera stadtmanae and Methanobrevibacter smithii
      activate human dendritic cells.
AB  - The methanoarchaea Methanosphaera stadtmanae and Methanobrevibacter smithii are
      known to be part of the indigenous human gut microbiota. Although the
      immunomodulatory effects of bacterial gut commensals have been studied
      extensively in the last decade, the impact of methanoarchaea in human's health
      and disease was rarely examined. Consequently, we studied and report here on the
      effects of M. stadtmanae and M. smithii on human immune cells. Whereas exposure
      to M. stadtmanae leads to substantial release of proinflammatory cytokines in
      monocyte-derived dendritic cells (moDCs), only weak activation was detected after
      incubation with M. smithii. Phagocytosis of M. stadtmanae by moDCs was
      demonstrated by confocal microscopy as well as transmission electronic microscopy
      (TEM) and shown to be crucial for cellular activation by using specific
      inhibitors. Both strains, albeit to different extents, initiate a maturation
      program in moDCs as revealed by up-regulation of the cell-surface receptors CD86
      and CD197 suggesting additional activation of adaptive immune responses.
      Furthermore, M. stadtmanae and M. smithii were capable to alter the gene
      expression of antimicrobial peptides in moDCs to different extents. Taken
      together, our findings strongly argue that the archaeal gut inhabitants M.
      stadtmanae and M. smithii are specifically recognized by the human innate immune
      system. Moreover, both strains are capable of inducing an inflammatory cytokine
      response to different extents arguing that they might have diverse
      immunomodulatory functions. In conclusion, we propose that the impact of
      intestinal methanoarchaea on pathological conditions involving the gut microbiota
      has been underestimated until now. 

PMID- 24915456
TI  - Native chemical ubiquitination using a genetically incorporated azidonorleucine.
AB  - A robust chemical ubiquitination method was developed. The method employed a
      genetically incorporated azidonorleucine as an orthogonal lysine precursor for
      the installation of a Gly residue bearing an Nalpha-auxiliary which mediated the
      ligation between ubiquitin(1-75)-thioester and the target protein. To demonstrate
      our methodology, a model protein, K48-linked diubiquitin, was synthesized with an
      overall yield of 35%. 

PMID- 24915457
TI  - The estrogen hypothesis of obesity.
AB  - The explanation of obesity as a simple result of positive energy balance fails to
      account for the scope of variable responses to diets and lifestyles. It is
      postulated that individual physiological and anatomical variation may be
      responsible for developing obesity. Girls in poor families develop greater
      adiposity than their male siblings, a trend not present in richer environments.
      This indicates strong influence of estrogen on fat accumulation irrespective of
      poor socioeconomic conditions. Obesity rates in males and females of developed
      nations are similar, while in poorer nations obesity is much more prevalent in
      females. Female to male ratio of obesity correlates inversely with gross domestic
      product. Therefore, the parity of male and female obesity in developed countries
      may result from male exposure to environmental estrogen-like substances
      associated with affluence. These hormonally driven mechanisms may be equally
      active within both sexes in more developed areas, thereby increasing overall
      obesity. 

PMID- 24915459
TI  - Infection with non-lethal West Nile virus Eg101 strain induces immunity that
      protects mice against the lethal West Nile virus NY99 strain.
AB  - Herein we demonstrate that infection of mice with West Nile virus (WNV) Eg101
      provides protective immunity against lethal challenge with WNV NY99. Our data
      demonstrated that WNV Eg101 is largely non-virulent in adult mice when compared
      to WNV NY99. By day 6 after infection, WNV-specific IgM and IgG antibodies, and
      neutralizing antibodies were detected in the serum of all WNV Eg101 infected
      mice. Plaque reduction neutralization test data demonstrated that serum from WNV
      Eg101 infected mice neutralized WNV Eg101 and WNV NY99 strains with similar
      efficiency. Three weeks after infection, WNV Eg101 immunized mice were challenged
      subcutaneously or intracranially with lethal dose of WNV NY99 and observed for
      additional three weeks. All the challenged mice were protected against disease
      and no morbidity and mortality was observed in any mice. In conclusion, our data
      for the first time demonstrate that infection of mice with WNV Eg101 induced high
      titers of WNV specific IgM and IgG antibodies, and cross-reactive neutralizing
      antibodies, and the resulting immunity protected all immunized animals from both
      subcutaneous and intracranial challenge with WNV NY99. These observations suggest
      that WNV Eg101 may be a suitable strain for the development of a vaccine in
      humans against virulent strains of WNV. 

PMID- 24915460
TI  - Sorting cells for basal and induced autophagic flux by quantitative ratiometric
      flow cytometry.
AB  - We detail here a protocol using tandem-tagged mCherry-EGFP-LC3 (C-G-LC3) to
      quantify autophagic flux in single cells by ratiometric flow cytometry and to
      isolate subpopulations of cells based on their relative levels of autophagic
      flux. This robust and sensitive method measures autophagic flux rather than
      autophagosome number and is an important addition to the autophagy researcher's
      array of tools for measuring autophagy. Two crucial steps in this protocol are i)
      generate cells constitutively expressing C-G-LC3 with low to medium fluorescence
      and low fluorescence variability, and ii) correctly set up gates and voltage/gain
      on a properly equipped flow cytometer. We have used this method to measure
      autophagic flux in a variety of cell types and experimental systems using many
      different autophagy stimuli. On a sorting flow cytometer, this technique can be
      used to isolate cells with different levels of basal autophagic flux, or cells
      with variable induction of flux in response to a given stimulus for further
      analysis or experimentation. We have also combined quantification of autophagic
      flux with methods to measure apoptosis and cell surface proteins, demonstrating
      the usefulness of this protocol in combination with other flow cytometry labels
      and markers. 

PMID- 24915461
TI  - Discovering hidden connections among diseases, genes and drugs based on
      microarray expression profiles with negative-term filtering.
AB  - Microarrays based on gene expression profiles (GEPs) can be tailored specifically
      for a variety of topics to provide a precise and efficient means with which to
      discover hidden information. This study proposes a novel means of employing
      existing GEPs to reveal hidden relationships among diseases, genes, and drugs
      within a rich biomedical database, PubMed. Unlike the co-occurrence method, which
      considers only the appearance of keywords, the proposed method also takes into
      account negative relationships and non-relationships among keywords, the
      importance of which has been demonstrated in previous studies. Three scenarios
      were conducted to verify the efficacy of the proposed method. In Scenario 1,
      disease and drug GEPs (disease: lymphoma cancer, lymph node cancer, and drug:
      cyclophosphamide) were used to obtain lists of disease- and drug-related genes.
      Fifteen hidden connections were identified between the diseases and the drug. In
      Scenario 2, we adopted different diseases and drug GEPs (disease: AML-ALL dataset
      and drug: Gefitinib) to obtain lists of important diseases and drug-related
      genes. In this case, ten hidden connections were identified. In Scenario 3, we
      obtained a list of disease-related genes from the disease-related GEP (liver
      cancer) and the drug (Capecitabine) on the PharmGKB website, resulting in twenty
      two hidden connections. Experimental results demonstrate the efficacy of the
      proposed method in uncovering hidden connections among diseases, genes, and
      drugs. Following implementation of the weight function in the proposed method, a
      large number of the documents obtained in each of the scenarios were judged to be
      related: 834 of 4028 documents, 789 of 1216 documents, and 1928 of 3791 documents
      in Scenarios 1, 2, and 3, respectively. The negative-term filtering scheme also
      uncovered a large number of negative relationships as well as non-relationships
      among these connections: 97 of 834, 38 of 789, and 202 of 1928 in Scenarios 1, 2,
      and 3, respectively. 

PMID- 24915463
TI  - Partially hydrolyzed bamboo (Phyllostachys heterocycla) as a porous Bioadsorbent
      for the removal of Pb(II) from aqueous mixtures.
AB  - A novel porous succinylated bioadsorbent was prepared by the partial enzymatic
      hydrolysis of bamboo (Phyllostachys heterocycla) and its subsequent modification
      with succinic anhydride. Pb(II) removal from solutions that also contained sodium
      chloride and an amino acid was investigated using the bioadsorbent. Enzymatic
      hydrolysis increased the number of accessible hydroxyl groups and surface area of
      the raw bamboo, and created many pores within the material. The porous
      succinylated bioadsorbent exhibited high efficiency for Pb(II) binding. The
      sodium chloride content significantly decreased the Pb(II) adsorption capacity,
      whereas a minor effect was observed in the presence of arginine. The experimental
      data could be accurately described by a pseudo-second-order kinetics model, and
      the adsorption proceeded via an ion exchange mechanism. Even in a solution
      containing sodium chloride and arginine, the maximum adsorption capacity of
      Pb(II) by the porous succinylated bioadsorbent was 99.5 mg/g at 303 K. 

PMID- 24915458
TI  - Peste des petits ruminants virus infection of small ruminants: a comprehensive
      review.
AB  - Peste des petits ruminants (PPR) is caused by a Morbillivirus that belongs to the
      family Paramyxoviridae. PPR is an acute, highly contagious and fatal disease
      primarily affecting goats and sheep, whereas cattle undergo sub-clinical
      infection. With morbidity and mortality rates that can be as high as 90%, PPR is
      classified as an OIE (Office International des Epizooties)-listed disease.
      Considering the importance of sheep and goats in the livelihood of the poor and
      marginal farmers in Africa and South Asia, PPR is an important concern for food
      security and poverty alleviation. PPR virus (PPRV) and rinderpest virus (RPV) are
      closely related Morbilliviruses. Rinderpest has been globally eradicated by mass
      vaccination. Though a live attenuated vaccine is available against PPR for
      immunoprophylaxis, due to its instability in subtropical climate (thermo
      sensitivity), unavailability of required doses and insufficient coverage (herd
      immunity), the disease control program has not been a great success. Further,
      emerging evidence of poor cross neutralization between vaccine strain and PPRV
      strains currently circulating in the field has raised concerns about the
      protective efficacy of the existing PPR vaccines. This review summarizes the
      recent advancement in PPRV replication, its pathogenesis, immune response to
      vaccine and disease control. Attempts have also been made to highlight the
      current trends in understanding the host susceptibility and resistance to PPR. 

PMID- 24915462
TI  - Post-traumatic multimodal brain monitoring: response to hypertonic saline.
AB  - Emerging evidence suggests that hypertonic saline (HTS) is efficient in
      decreasing intracranial pressure (ICP). However there is no consensus about its
      interaction with brain hemodynamics and oxygenation. In this study, we
      investigated brain response to HTS bolus with multimodal monitoring after severe
      traumatic brain injury (TBI). We included 18 consecutive TBI patients during 10
      days after neurocritical care unit admission. Continuous brain monitoring applied
      included ICP, tissue oxygenation (PtO2) and cerebral blood flow (CBF). Cerebral
      perfusion pressure (CPP), cerebrovascular resistance (CVR), and reactivity
      indices related to pressure (PRx) and flow (CBFx) were calculated. ICM+software
      was used to collect and analyze monitoring data. Eleven of 18 (61%) patients
      developed 99 episodes of intracranial hypertension (IHT) greater than 20 mm Hg
      that were managed with 20% HTS bolus. Analysis over time was performed with
      linear mixed-effects regression modelling. After HTS bolus, ICP and CPP improved
      over time (p<0.001) following a quadratic model. From baseline to 120 min, ICP
      had a mean decrease of 6.2 mm Hg and CPP a mean increase of 3.1 mmHg. Mean
      increase in CBF was 7.8 mL/min/100 g (p<0.001) and mean decrease in CVR reached
      0.4 mm Hg*min*100 g/mL (p=0.01). Both changes preceded pressures improvement.
      PtO2 exhibited a marginal increase and no significant models for time behaviour
      could be fitted. PRx and CBFx were best described by a linear decreasing model
      showing autoregulation recover after HTS (p=0.01 and p=0.04 respectively). During
      evaluation, CO2 remained constant and sodium level did not exhibit significant
      variation. In conclusion, management of IHT with 20% HTS significantly improves
      cerebral hemodynamics and cerebrovascular reactivity with recovery of CBF
      appearing before rise in CPP and decrease in ICP. In spite of cerebral
      hemodynamic improvement, no significant changes in brain oxygenation were
      identified.

PMID- 24915464
TI  - Melanocytic nevi as biomarkers of breast cancer risk.

PMID- 24915455
TI  - The brain and brown fat.
AB  - Brown adipose tissue (BAT) is a specialized organ responsible for thermogenesis,
      a process required for maintaining body temperature. BAT is regulated by the
      sympathetic nervous system (SNS), which activates lipolysis and mitochondrial
      uncoupling in brown adipocytes. For many years, BAT was considered to be
      important only in small mammals and newborn humans, but recent data have shown
      that BAT is also functional in adult humans. On the basis of this evidence,
      extensive research has been focused on BAT function, where new molecules, such as
      irisin and bone morphogenetic proteins, particularly BMP7 and BMP8B, as well as
      novel central factors and new regulatory mechanisms, such as orexins and the
      canonical ventomedial nucleus of the hypothalamus (VMH) AMP- activated protein
      kinase (AMPK)-SNS-BAT axis, have been discovered and emerged as potential drug
      targets to combat obesity. In this review we provide an overview of the complex
      central regulation of BAT and how different neuronal cell populations co
      ordinately work to maintain energy homeostasis. 

PMID- 24915465
TI  - Impact of childhood cancer on maternal employment in Japan.
AB  - BACKGROUND: Family members of children with cancer experience various long-term
      effects as a result of cancer diagnosis and treatment. Therefore, comprehensive
      and long-term support is needed. As the employment rate of women has increased in
      recent years, support for working mothers with children diagnosed with cancer is
      also required. OBJECTIVE: We investigated the following issues and relevant
      changes that working mothers of children diagnosed with cancer must deal with:
      (1) work change, (2) stress, (3) social support, (4) work motivation, and (5)
      employment status after diagnosis. METHODS: A cross-sectional exploratory study
      design was used. Data were collected from 62 mothers of children who were
      diagnosed with cancer using self-report questionnaires. RESULTS: Of the 32
      mothers who worked at the time of diagnosis, 10 continued to work, 12 took an
      extended leave, and 10 quit working, and 70% lost motivation for work following
      diagnosis. Half of mothers who continued to work during treatment reported
      financial reasons. CONCLUSIONS: These findings indicate that mothers who quit
      work following diagnosis did not initially consider a long leave of absence. Even
      mothers who continued to work during treatment desired a long leave of absence to
      care for their children. IMPLICATIONS FOR PRACTICE: Nurses should provide mothers
      with explanations of the prospects after the completion of cancer treatment and
      determine their expectations for their lifestyle and work during treatment. We
      recommend that nurses confirm mothers' willingness to take a long leave of
      absence from work and give relevant advice about seeking financial assistance.

PMID- 24915466
TI  - Preferences for Aggressive End-of-life Care and Their Determinants Among
      Taiwanese Terminally Ill Cancer Patients.
AB  - BACKGROUND: Studies on factors influencing preferences for aggressive end-of-life
      (EOL) care have focused predominantly on preferred goals of EOL and seldom
      comprehensively incorporate patients' predisposing, enabling, and need factors
      into their analyses. OBJECTIVE: The aim of this study was to investigate the
      determinants of preferences for a wide range of aggressive EOL care from the
      aforementioned factors. METHODS: A cross-sectional survey was conducted using a
      convenience sample of 2329 terminally ill cancer patients recruited from 23
      hospitals throughout Taiwan. RESULTS: Among these Taiwanese terminally ill cancer
      patients, 8.2% preferred prolonging life as their goal for EOL care. When
      combining those who wanted and those who were undecided as wanting that specific
      treatment, 27.9% preferred cardiopulmonary resuscitation when their life was in
      danger, and 36.0%, 27.3%, 24.3%, and 26.7% preferred to receive care at intensive
      care unit, cardiac massage, intubation, and mechanical ventilation support,
      respectively. Those at risk of preferring aggressive EOL care were men, younger
      than 45 years, married, diagnosed within 6 months, and with comorbidity and their
      physician had not accurately disclosed their prognosis or discussed EOL care
      issues to/with them. CONCLUSIONS: Few Taiwanese terminally ill cancer patients
      preferred to prolong life as their goal for EOL care, cardiopulmonary
      resuscitation when their life was in danger, and life-sustaining treatments at
      EOL. Preferences for aggressive EOL care are determined by patients'
      predisposing, enabling, and need factors. IMPLICATIONS FOR PRACTICE: Terminally
      ill cancer patients at risk of preferring aggressive EOL care should receive
      interventions to help them appropriately weigh the burdens and benefits of such
      aggressive treatments.

PMID- 24915467
TI  - Rapamycin prevents strong phosphorylation of p53 on serine 46 and attenuates
      activation of the p53 pathway in A549 lung cancer cells exposed to actinomycin D.
AB  - The activation of the p53 pathway by 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR), a molecule that mimics metabolic stress, is attenuated by
      rapamycin, an inhibitor of mTOR kinase, immunosuppressant, and cancer drug.
      Rapamycin also extends lifespan in experimental animals. Because AICAR is a
      relatively weak activator of p53, we investigated whether stimulation of p53 by
      the strong activator actinomycin D is also sensitive to the inhibitory effect of
      rapamycin. In A549 lung cancer cells, activation of p53 by actinomycin D was
      associated with phosphorylation of p53 on Ser46. Rapamycin inhibited the
      accumulation of phospho-Ser46 p53, attenuated upregulation of some p53 target
      genes, and altered cell-cycle progression. Moreover, in cells exposed to
      actinomycin D, rapamycin attenuated the accumulation of PML, a protein that in
      some conditions stimulates Ser46 phosphorylation. However, Ser46 phosphorylation
      was not diminished in PML-knockdown cells, suggesting that in our system PML does
      not play a major role in stimulating p53 phosphorylation on Ser46. Knockdown of
      p53 diminished the upregulation of PML by stress-inducing agents, consistent with
      the idea that PML is a p53-regulated gene. Our data suggest that the attenuation
      of p53 phosphorylation on Ser46 may play a significant role in the biological
      activity of anti-aging rapamycin. 

PMID- 24915469
TI  - Effect of reaction mechanism on precursor exposure time in atomic layer
      deposition of silicon oxide and silicon nitride.
AB  - Atomic layer deposition (ALD) of highly conformal, silicon-based dielectric thin
      films has become necessary because of the continuing decrease in feature size in
      microelectronic devices. The ALD of oxides and nitrides is usually thought to be
      mechanistically similar, but plasma-enhanced ALD of silicon nitride is found to
      be problematic, while that of silicon oxide is straightforward. To find why, the
      ALD of silicon nitride and silicon oxide dielectric films was studied by applying
      ab initio methods to theoretical models for proposed surface reaction mechanisms.
      The thermodynamic energies for the elimination of functional groups from
      different silicon precursors reacting with simple model molecules were calculated
      using density functional theory (DFT), explaining the lower reactivity of
      precursors toward the deposition of silicon nitride relative to silicon oxide
      seen in experiments, but not explaining the trends between precursors. Using more
      realistic cluster models of amine and hydroxyl covered surfaces, the structures
      and energies were calculated of reaction pathways for chemisorption of different
      silicon precursors via functional group elimination, with more success. DFT
      calculations identified the initial physisorption step as crucial toward
      deposition and this step was thus used to predict the ALD reactivity of a range
      of amino-silane precursors, yielding good agreement with experiment. The
      retention of hydrogen within silicon nitride films but not in silicon oxide
      observed in FTIR spectra was accounted for by the theoretical calculations and
      helped verify the application of the model. 

PMID- 24915468
TI  - Similar patterns of clonally expanded somatic mtDNA mutations in the colon of
      heterozygous mtDNA mutator mice and ageing humans.
AB  - Clonally expanded mitochondrial DNA (mtDNA) mutations resulting in focal
      respiratory chain deficiency in individual cells are proposed to contribute to
      the ageing of human tissues that depend on adult stem cells for self-renewal;
      however, the consequences of these mutations remain unclear. A good animal model
      is required to investigate this further; but it is unknown whether mechanisms for
      clonal expansion of mtDNA mutations, and the mutational spectra, are similar
      between species. Here we show that mice, heterozygous for a mutation disrupting
      the proof-reading activity of mtDNA polymerase (PolgA(+/mut)) resulting in an
      increased mtDNA mutation rate, accumulate clonally expanded mtDNA point mutations
      in their colonic crypts with age. This results in focal respiratory chain
      deficiency, and by 81 weeks of age these animals exhibit a similar level and
      pattern of respiratory chain deficiency to 70-year-old human subjects.
      Furthermore, like in humans, the mtDNA mutation spectrum appears random and there
      is an absence of selective constraints. Computer simulations show that a random
      genetic drift model of mtDNA clonal expansion can accurately model the data from
      the colonic crypts of wild-type, PolgA(+/mut) animals, and humans, providing
      evidence for a similar mechanism for clonal expansion of mtDNA point mutations
      between these mice and humans. 

PMID- 24915470
TI  - Minimum clinically important difference in diffusing capacity of the lungs for
      carbon monoxide among patients with severe and very severe chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: The minimum clinically important difference (MCID) for diffusing
      capacity of the lungs for carbon monoxide (DLCO) has not yet been solidly
      established. METHODS: We used the dataset of surgical cohort of National
      Emphysema Treatment Trial. Briefly, severe and very severe chronic obstructive
      pulmonary disease (COPD) patients who were candidate for volume reduction surgery
      and who could provide sufficient data at 12-month follow-up were included. We
      used two anchor methods using 6-minute walk distance (6MWD. MCID = 40 m) and
      forced expiratory volume in 1 sec (FEV1. MCID = 100 ml) as anchors, and two
      distribution methods. We proposed MCID with a median of estimated values. We
      estimated MCID for DLCO in raw value and % change from the baseline
      independently. RESULTS: The surgical cohort included 356 patients, whose average
      age was 66.6 +/- 5.5 years, and the average % predicted FEV1 was 27.8 +/- 7.3%.
      The estimated MCID for DLCO in raw value and % change from the baseline were as
      follows: anchor method (average, 6MWD) 1.2 ml/min/mmHg, 17%; anchor method
      (average, FEV1) 0.7 ml/min/mmHg, 11%; anchor method (receiver operating
      characteristic, 6MWD) 1.1 ml/min/mmHg, 10%; anchor method (receiver operating
      characteristic, FEV1) 1.2 ml/min/mmHg, 3%; distribution method (0.3 units of
      standard deviation), 0.9 ml/min/mmHg, 11%; distribution method (standard error of
      measurement), 1.1 ml/min/mmHg. The median of these values was 1.1 ml/min/mmHg and
      11%. CONCLUSION: We estimated the group-level MCID for DLCO for patients with
      severe and very severe COPD patients as 1.1 ml/min/mmHg and 11% of baseline DLCO.

PMID- 24915471
TI  - Psychosocial framework for understanding psychological distress among survivors
      of the November 26, 2008 Mumbai terror attack: beyond traumatic experiences and
      emergency medical care.
AB  - The field of "Public Health in Disasters and Complex Emergencies" is replete with
      either epidemiological studies or studies in the area of hospital preparedness
      and emergency care. The field is dominated by hospital-based or emergency phase
      related literature, with very little attention on long-term health and mental
      health consequences. The social science, or the public mental health perspective,
      too, is largely missing. It is in this context that the case report of the
      November 26, 2008 Mumbai terror attack survivors is presented to bring forth the
      multi-dimensional and dynamic long-term impacts, and their consequences for
      psychological well-being, two years after the incident. Based on literature, the
      report formulates a theoretical framework through which the lived experiences of
      the survivors is analyzed and understood from a social science perspective. This
      report is an outcome of the ongoing work with the survivors over a period of two
      years. A mixed methodology was used. It quantitatively captures the experience of
      231 families following the attack, and also uses a self-reporting questionnaire
      (SRQ), SRQ20, to understand the psychological distress. In-depth qualitative case
      studies constructed from the process records and in-depth interviews focus on
      lived experiences of the survivors and explain the patterns emerging from the
      quantitative analysis. This report outlines the basic profile of the survivors,
      the immediate consequences of the attack, the support received, psychological
      consequences, and the key factors contributing to psychological distress. Through
      analysis of the key factors and the processes emerging from the lived experiences
      that explain the progression of vulnerability to psychological distress, this
      report puts forth a psychosocial framework for understanding psychological
      distress among survivors of the November 26, 2008 Mumbai terror attack.

PMID- 24915472
TI  - Learning curves in highly skilled chess players: a test of the generality of the
      power law of practice.
AB  - The power law of practice holds that a power function best interrelates skill
      performance and amount of practice. However, the law's validity and generality
      are moot. Some researchers argue that it is an artifact of averaging individual
      exponential curves while others question whether the law generalizes to complex
      skills and to performance measures other than response time. The present study
      tested the power law's generality to development over many years of a very
      complex cognitive skill, chess playing, with 387 skilled participants, most of
      whom were grandmasters. A power or logarithmic function best fit grouped data but
      individuals showed much variability. An exponential function usually was the
      worst fit to individual data. Groups differing in chess talent were compared and
      a power function best fit the group curve for the more talented players while a
      quadratic function best fit that for the less talented. After extreme amounts of
      practice, a logarithmic function best fit grouped data but a quadratic function
      best fit most individual curves. Individual variability is great and the power
      law or an exponential law are not the best descriptions of individual chess skill
      development. 

PMID- 24915474
TI  - Short and sweet.

PMID- 24915473
TI  - Redox-triggered C-C coupling of alcohols and vinyl epoxides: diastereo- and
      enantioselective formation of all-carbon quaternary centers via tert-(hydroxy)
      prenylation.
AB  - Iridium catalyzed primary alcohol oxidation triggers reductive C-O bond cleavage
      of isoprene oxide to form aldehyde-allyliridium pairs that combine to form
      products of tert-(hydroxy)-prenylation, a motif found in >2000 terpenoid natural
      products. Curtin-Hammett effects are exploited to enforce high levels of anti
      diastereo- and enantioselectivity in the formation of an all-carbon quaternary
      center. The present redox-triggered carbonyl additions occur in the absence of
      stoichiometric byproducts, premetalated reagents, and discrete alcohol-to
      aldehyde redox manipulations. 

PMID- 24915475
TI  - Difficult patients: exploring the patient perspective.
AB  - BACKGROUND AND OBJECTIVES: Patients experienced as difficult comprise at least
      15% of ambulatory visits. To better understand these challenging relationships,
      we explored the patients' perspectives about their relationships with their
      doctors. METHODS: Using a cross-sectional study design, we surveyed patients
      regarding their perception of their doctor-patient relationship using five
      questions graded on a 7-point Likert scale. Family medicine residents
      subjectively determined which of their patients were "difficult." This patient
      "difficulty" status was linked to the patient survey's data through anonymous
      coding. RESULTS: A total of 161 patients participated, for a response rate of
      60%. Of these patients, 20% were perceived as difficult. Two sample t test
      comparison of means revealed that difficult patients reported greater ease in
      communication. After adjusting for demographics and individual characteristics,
      Generalized Linear Model (GLM) uncovered that men reported a harder time talking
      with their doctor, thought their problems were more challenging, and felt less in
      control of their health care decisions. Gender was a stronger predictor than
      perceived difficult status for patients' perceptions of poorer quality
      relationships with providers. CONCLUSIONS: Surprisingly, difficult patients
      overall reported greater ease of communication with their residents than non
      difficult patients. The pronounced discordance between the perspectives of
      physicians and patients likely underlies much of the frustration experienced by
      clinicians. Since difficult patients seem satisfied with the resident-patient
      relationship, further work is needed to understand this discrepancy and improve
      physician ease and satisfaction with these challenging relationships.

PMID- 24915477
TI  - An off-site clinical pharmacy service in family medicine: development and 1-year
      outcomes.
AB  - BACKGROUND AND OBJECTIVES: Clinical pharmacists are a part of integrated health
      care teams and provide clinical medication recommendations for family physicians.
      On-site clinical pharmacy services are common in family medicine. This model may
      not be the most effective or efficient way to provide clinical pharmacy services
      in a small practice or in a remote location. The objectives of this study were to
      describe the development of an off-site clinical pharmacy service and to describe
      the 1-year clinical impact of this service. METHODS: The University of Colorado
      Park Meadows Family Medicine Clinic is located approximately 15 miles from the
      Anschutz Medical Campus. In July 2011, a clinical pharmacist implemented clinical
      pharmacy services with the goal of providing medication expertise primarily using
      an off-site model. The clinical pharmacist prospectively screened patients with
      appointments and provided medication recommendations in the electronic medical
      record for providers to consider at the patient appointment. RESULTS: For the
      first 12 months, the clinical pharmacist spent 118 hours providing the clinical
      pharmacy service. A total of 315 medication recommendations were made for 123
      patients; 69.8% were implemented. Forty-nine vaccinations were administered, and
      24 potentially dangerous major drug-drug interactions were identified and
      resolved. Thirty-one unnecessary high-cost drugs were discontinued, resulting in
      estimated annual savings of $52,215.36. CONCLUSIONS: Our data indicate that
      clinical pharmacy services can be implemented for smaller remote family clinics
      using an offsite model. Within this model, clinical pharmacy interventions
      optimized medication use, managed serious drug interactions, and resulted in cost
      avoidance.

PMID- 24915476
TI  - Student specialty plans, clinical decision making, and health care reform.
AB  - BACKGROUND AND OBJECTIVES: Health care reform aims to increase evidence-based,
      cost-conscious, and patient-centered care. Family medicine is seen as central to
      these aims in part due to evidence of lower cost and comparable quality care
      compared with other specialties. We sought evidence that senior medical students
      planning family medicine residency differ from peers entering other fields in
      decision-making patterns relevant to these health care reform aims. METHODS: We
      conducted a national, anonymous, internet-based survey of senior medical
      students. Students chose one of two equivalent management options for a set of
      patient vignettes based on preventive care, medication selection, or initial
      chronic disease management scenarios, representing in turn evidence-based care,
      cost-conscious care, and patient-centered care. We examined differences in
      student recommendations, comparing those planning to enter family medicine with
      all others using bivariate and weighted, multilevel, multivariable analyses.
      RESULTS: Among 4,656 surveys received from seniors at 84 participating medical
      schools, students entering family medicine were significantly more likely to
      recommend patient management options that were more cost conscious and more
      patient centered. We did not find a significant difference between the student
      groups in recommendations for evidence-based care vignettes. CONCLUSIONS: This
      study provides preliminary evidence suggesting that students planning to enter
      family medicine may already have clinical decision-making patterns that support
      health care reform goals to a greater extent than their peers. If confirmed by
      additional studies, this could have implications for medical school admission and
      training processes.

PMID- 24915478
TI  - Structure and characteristics of family medicine maternity care fellowships.
AB  - BACKGROUND AND OBJECTIVES: Fewer family physicians are providing maternity care.
      Maternity Care Fellowships (MCFs) provide training in advanced obstetrical
      skills, including cesarean sections. These programs lack official recognition and
      certification. MCF graduates have been studied, but there are no studies of the
      fellowships. The objective of this study was to assess the structure and
      organization of family medicine MCFs. METHODS: We identified MCFs from the
      American Academy of Family Physicians website. Twenty-nine unique and active
      programs were included in the final sample. We surveyed programs via an anonymous
      internet methodology. The survey asked about program structure, organization, and
      educational aspects of the program. RESULTS: A total of 18 programs responded,
      for a 62% response rate. Eighty-eight percent of MCFs were 1 year in length, and
      the mean number of fellows per year was 1.9. All but one program were associated
      with a residency training program, and 55.6% were based in community hospitals.
      All but two programs had a standardized curriculum. Eighty-eight percent of MCFs
      had obstetricians involved in teaching or clinical supervision. Mean estimated
      number of deliveries performed by fellows were 80 vaginal and 108 caesarian.
      Graduates of MCFs were largely able to obtain caesarian privileges after
      graduation, and many were working in rural and/or underserved areas. Many MCF
      directors favored formal accreditation and a standardized curriculum across
      programs. CONCLUSIONS: Despite lack of formal accreditation, MCFs have academic
      affiliations and internally standardized curricula. MCFs provide an obstetric
      workforce for rural and underserved areas, and formal accreditation may ensure
      program survival and boost educational standards.

PMID- 24915479
TI  - Are specific residency program characteristics associated with the pass rate of
      graduates on the ABFM certification examination?
AB  - BACKGROUND AND OBJECTIVES: Board certification has become an accepted measure of
      physician quality. The effect of both non-curricular and curricular residency
      program characteristics on certification rates has not been previously studied.
      The purpose of this study is to evaluate the effect of various program
      characteristics on first-time American Board of Family Medicine (ABFM) pass
      rates. METHODS: Using information from the American Academy of Family Physicians
      (AAFP), National Resident Matching Program (NRMP), and FREIDA(r), program
      characteristics were obtained. Three-year and 5-year aggregate ABFM board pass
      rates were calculated. Descriptive statistics were used to summarize the data.
      The relationship between program characteristics, initial Match rates, and non
      Accreditation Council for Graduate Medical Education (ACGME) required activities
      (NRCA), and first-time Board pass rates were analyzed using chi-square.
      Significance was defined as P<.05 level of confidence. RESULTS: Fifty-two percent
      of residency programs have ABFM board pass rates ? 90%. Both 3- and 5-year
      aggregate Board pass rates were significantly associated with regional location,
      program size, accreditation cycle length, and any NRCA, specifically including
      international experiences and curriculum in alternative medicine. Location type
      (urban, suburban, rural, or inner city), program structure, salary, moonlighting,
      available tracks, and P4 participation were not associated. CONCLUSIONS: The
      percent of first-time takers successfully completing the ABFM examination is
      associated with several residency program characteristics, including regional
      location, program size, accreditation cycle length, opportunities for
      international experiences, and training in alternative medicine.

PMID- 24915480
TI  - FM POD: an evidence-based blended teaching skills program for rural preceptors.
AB  - BACKGROUND AND OBJECTIVES: The University of Calgary's Rural Integrated Community
      Clerkship anchors final-year medical student education in 9 months of family
      medicine. The purpose of this pilot study was to evaluate the Family Medicine
      Preceptor Online Development (FM POD) program, designed to meet the faculty
      development needs of rural preceptors facing challenges of geographical
      distribution and time constraints. METHODS: The theoretically based program used
      a blended learning approach, beginning with a face-to-face workshop to strengthen
      participants' social presence during online interactions to follow. Asynchronous
      narrated presentations supplied foundational knowledge prior to facilitated
      synchronous web conferences, where participants shared experiences and co
      constructed new knowledge. The program was evaluated using mixed methods,
      including surveys and focus group discussion. RESULTS: Evaluation tools generated
      data with high internal consistency reliability; focus group information
      substantiated and enriched the quantitative survey data. Participants enjoyed
      collaborating with colleagues and rated their learning experiences highly,
      reporting meaningful and statistically significant increases in mean comfort with
      all the precepting skills taught: giving effective feedback, using questions to
      teach, teaching communications skills, helping learners in difficulty, and making
      teaching time-efficient. All effect sizes were large. Increased comfort with
      distance learning technologies was a positive consequence. CONCLUSIONS: Results
      support the applicability of principles of social constructivism, experiential
      learning, and reflective learning in these participants. The program was highly
      rated and effectively increased participants' comfort with teaching skills,
      offering practical off-the-peg modular faculty development in basic teaching
      skills for distributed faculty. Participants appreciated the flexible delivery
      format, which course developers found readily adaptable for additional topics.

PMID- 24915481
TI  - Family physicians' opinions on the primary care documentation, coding, and
      billing system: a qualitative study from the residency research network of Texas.
AB  - BACKGROUND AND OBJECTIVES: The study's aim was to deepen our understanding of
      family physicians' perceptions of the strengths and weaknesses of the widely used
      US documentation, coding, and billing rules for primary care evaluation and
      management (E/M) services. METHODS: This study used in-depth, qualitative
      interviews of 32 family physicians in urban and rural, academic, and private
      practices. Interviews were initiated with a series of grand tour questions asking
      participants to give examples and personal narratives demonstrating cost
      efficiencies and cost inefficiencies relating to the E/M rules in their own
      practices. Investigators independently used an immersion-crystallization approach
      to analyze transcripts to search for unifying themes and subthemes until
      consensus among investigators was achieved. RESULTS: The majority of participants
      reported that the documentation rules, coding rules, and common fees for
      procedures and preventive services were reasonable. The E/M documentation rules
      for all other visit types, however, were perceived by the participants as
      unnecessarily complicated and unclear. The existing codes did not describe the
      actual work for common clinic visits, which led to documenting and coding by
      heuristics and patterns. Participants reported inadequate payment for complex
      patients, multiple patient concerns in a single office visit, services requiring
      extra time beyond a standard office visit, non-face-to-face time, and others. The
      E/M rules created unintended negative consequences such as family physicians not
      accepting Medicare or Medicaid patients, inaccurate documentation, poor-quality
      care, and system inefficiencies such as unnecessary tests and referrals.
      CONCLUSIONS: Family physicians expressed many problems and frustrations with the
      existing E/M documentation, coding, and billing rules and felt the system
      undervalued and unappreciated them for the complex and comprehensive care they
      provide. Findings of this study could inform improved guidelines for primary care
      documentation, coding, and billing.

PMID- 24915482
TI  - The kumquat and other words for brain tumor.

PMID- 24915483
TI  - What patients give us: one story of the doctor-patient relationship.

PMID- 24915484
TI  - My top 10 misconceptions about international health.

PMID- 24915486
TI  - Elucidation of band structure of charge storage in conducting polymers using a
      redox reaction.
AB  - A novel technique to investigate charge storage characteristics of intrinsically
      conducting polymer films has been developed. A redox reaction is conducted on a
      polymer film on a rotating disk electrode under potentiostatic condition so that
      the rate of charging of the film equals the rate of removal of the charge by the
      reaction. The voltammogram obtained from the experiment on polyaniline film using
      Fe(2+)/Fe(3+) in HCl as the redox system shows five distinct linear segments
      (bands) with discontinuity in the slope at specific transition potentials. These
      bands are the same as those indicated by electron spin resonance (ESR)/Raman
      spectroscopy with comparable transition potentials. From the dependence of the
      slopes of the bands on concentration of ferrous and ferric ions, it was possible
      to estimate the energies of the charge carriers in different bands. The film
      behaves as a redox capacitor and does not offer resistance to charge transfer and
      electronic conduction. 

PMID- 24915487
TI  - Long-range ordered graphite oxide liquid crystals.
AB  - Liquid crystallinity of graphite oxide (GtO) flakes prepared without the need for
      sonication was found. Therefore, the scalable processing of GtO liquid crystals
      (LCs) became promising. The spontaneous highly-ordered alignment of GtO LCs was
      observed, as verified by SEM and TEM. The effects of electric fields on GtO LCs
      were demonstrated. 

PMID- 24915485
TI  - The effect of macromolecular crowding on the electrostatic component of barnase
      barstar binding: a computational, implicit solvent-based study.
AB  - Macromolecular crowding within the cell can impact both protein folding and
      binding. Earlier models of cellular crowding focused on the excluded volume,
      entropic effect of crowding agents, which generally favors compact protein
      states. Recently, other effects of crowding have been explored, including
      enthalpically-related crowder-protein interactions and changes in solvation
      properties. In this work, we explore the effects of macromolecular crowding on
      the electrostatic desolvation and solvent-screened interaction components of
      protein-protein binding. Our simple model enables us to focus exclusively on the
      electrostatic effects of water depletion on protein binding due to crowding,
      providing us with the ability to systematically analyze and quantify these
      potentially intuitive effects. We use the barnase-barstar complex as a model
      system and randomly placed, uncharged spheres within implicit solvent to model
      crowding in an aqueous environment. On average, we find that the desolvation free
      energy penalties incurred by partners upon binding are lowered in a crowded
      environment and solvent-screened interactions are amplified. At a constant
      crowder density (fraction of total available volume occupied by crowders), this
      effect generally increases as the radius of model crowders decreases, but the
      strength and nature of this trend can depend on the water probe radius used to
      generate the molecular surface in the continuum model. In general, there is huge
      variation in desolvation penalties as a function of the random crowder positions.
      Results with explicit model crowders can be qualitatively similar to those using
      a lowered "effective" solvent dielectric to account for crowding, although the
      "best" effective dielectric constant will likely depend on multiple system
      properties. Taken together, this work systematically demonstrates, quantifies,
      and analyzes qualitative intuition-based insights into the effects of water
      depletion due to crowding on the electrostatic component of protein binding, and
      it provides an initial framework for future analyses. 

PMID- 24915488
TI  - Interfacial self-assembled functional nanoparticle array: a facile surface
      enhanced Raman scattering sensor for specific detection of trace analytes.
AB  - Surface-enhanced Raman scattering (SERS) has proven to be promising for the
      detection of trace analytes; however, the precise nanofabrication of a specific
      and sensitive plasmonic SERS-active substrate is still a major challenge that
      limits the scope of its applications. In this work, gold nanoparticles are self
      assembled into densely packed two-dimensional arrays at a liquid/liquid interface
      between dimethyl carbonate and water in the absence of template controller
      molecules. Both the simulation and experiment results show that the particles
      within these film-like arrays exhibit strong electromagnetic coupling and enable
      large amplification of Raman signals. In order to realize the level of sensing
      specificity, the surface chemistry of gold nanoparticles (Au NPs) is rationally
      tailored by incorporating an appropriate chemical moiety that specifically
      captures molecules of interest. The ease of fabrication and good uniformity make
      this platform ideal for in situ SERS sensing of trace targets in complex samples.

PMID- 24915489
TI  - Different scoring systems in predicting survival in Chinese patients with liver
      cirrhosis undergoing transjugular intrahepatic portosystemic shunt.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an
      established minimal-invasive procedure to treat complications of portal
      hypertension, and several scoring systems have been used to help choose suitable
      patients. However, its accuracy remains controversial. AIM: To compare the
      performance of the Child-Turcotte-Pugh (CTP) classification system, model for end
      stage liver disease (MELD) score, Emory score, Bonn TIPS early mortality (BOTEM)
      score, and serum bilirubin and platelet count (SB/PLT model) in predicting
      survival in Chinese patients with liver cirrhosis undergoing TIPS. PATIENTS AND
      METHODS: The clinical data of patients undergoing TIPS in our department were
      retrospectively analyzed to compare the five scoring systems on the basis of
      survival after TIPS. RESULTS: A cohort of 159 patients was analyzed. The survival
      curves showed a statistical significance between classification B and C of CTP
      (chi=9.451, P=0.002), between MELD less than 10 and MELD at least 10 (chi=10.099,
      P=0.001), and between low-risk and moderate-risk groups of the Emory score
      (chi=4.656, P=0.031), indicating a better discriminatory ability. By ROC curves
      and a logistic regression model, the MELD score and the CTP system had better
      power to predict 3-, 12-, and 24-month survival. The MELD score and the CTP
      classification system had smaller values of -2 Ln(L), Akaike Information
      criterion, and Schwarz-Bayesian criterion, respectively. CONCLUSION: The MELD
      score and the CTP classification system provide better prognostic stratification
      for a cohort of Chinese patients with advanced cirrhosis undergoing TIPS.
      However, the MELD score is not significantly superior to the CTP system.

PMID- 24915490
TI  - Pancreatitis-associated protein has no additional value as a marker of disease
      activity in a real-life cohort of IBD patients.
AB  - BACKGROUND AND AIM: Monitoring of mucosal inflammation in inflammatory bowel
      disease (IBD) is of major importance. New noninvasive markers for intestinal
      inflammation are needed. Previous studies have reported that pancreatitis
      associated protein (PAP) correlates with clinical activity in IBD subgroups. Our
      aim was to investigate the correlation of serum and fecal PAP with clinical and
      biochemical parameters of disease activity in a real-life IBD cohort. PATIENTS
      AND METHODS: Two hundred and five consecutive IBD patients were enrolled.
      Clinical disease activity was scored by the Harvey-Bradshaw Index or the Simple
      Clinical Colitis Activity Index; also, C-reactive protein (CRP), erythrocyte
      sedimentation rate, and fecal calprotectin were determined. As surrogate for
      endoscopy, a combination score of clinical indices with CRP or calprotectin was
      used to define active disease. Fecal and serum PAP were measured by ELISA.
      RESULTS: The median serum and fecal PAP did not differ in Crohn's disease (CD) or
      ulcerative colitis (UC) patients with active compared with inactive disease
      according to clinical activity indices. Defining active disease by a combination
      score of Harvey-Bradshaw Index of more than 4 and CRP of more than 5 mg/l or
      calprotectin more than 250 ug/g, serum PAP (P=0.01), but not fecal PAP (P=0.32),
      was significantly higher in active than inactive CD patients. Area under the
      curve of the corresponding receiver operating curve (ROC) was 0.64. No
      differences were found in serum or fecal PAP levels using the combination score
      for active disease in UC. CONCLUSION: Serum but not fecal PAP was higher in
      active compared with nonactive CD and may reflect mucosal inflammation in CD, but
      not in UC. However, the accuracy of serum PAP for the diagnosis of active disease
      was poor, and therefore, serum PAP does not seem to have additional value
      compared with the current noninvasive markers.

PMID- 24915491
TI  - Comparative transcriptional analysis of asexual and sexual morphs reveals
      possible mechanisms in reproductive polyphenism of the cotton aphid.
AB  - Aphids, the destructive insect pests in the agriculture, horticulture and
      forestry, are capable of reproducing asexually and sexually upon environmental
      change. However, the molecular basis of aphid reproductive mode switch remains an
      enigma. Here we report a comparative analysis of differential gene expression
      profiling among parthenogenetic females, gynoparae and sexual females of the
      cotton aphid Aphis gossypii, using the RNA-seq approach with next-generation
      sequencing platforms, followed by RT-qPCR. At the cutoff criteria of fold change
      >=2 and P<0.01, we identified 741 up- and 879 down-regulated genes in gynoparae
      versus parthenogenetic females, 2,101 up- and 2,210 down-regulated genes in
      sexual females compared to gynoparae, and 1,614 up- and 2,238 down-regulated
      genes in sexual females relative to parthenogenetic females. Gene ontology
      category and KEGG pathway analysis suggest the involvement of differentially
      expressed genes in multiple cellular signaling pathways into the reproductive
      mode transition, including phototransduction, cuticle composition, progesterone
      mediated oocyte maturation and endocrine regulation. This study forms a basis for
      deciphering the molecular mechanisms underlying the shift from asexual to sexual
      reproduction in the cotton aphid. It also provides valuable resources for future
      studies on this host-alternating aphid species, and the insight into the
      understanding of reproductive mode plasticity in different aphid species. 

PMID- 24915492
TI  - Modeling adsorption and reactions of organic molecules at metal surfaces.
AB  - CONSPECTUS: The understanding of adsorption and reactions of (large) organic
      molecules at metal surfaces plays an increasingly important role in modern
      surface science and technology. Such hybrid inorganic/organic systems (HIOS) are
      relevant for many applications in catalysis, light-emitting diodes, single
      molecule junctions, molecular sensors and switches, and photovoltaics. Obviously,
      the predictive modeling and understanding of the structure and stability of such
      hybrid systems is an essential prerequisite for tuning their electronic
      properties and functions. At present, density-functional theory (DFT) is the most
      promising approach to study the structure, stability, and electronic properties
      of complex systems, because it can be applied to both molecules and solids
      comprising thousands of atoms. However, state-of-the-art approximations to DFT do
      not provide a consistent and reliable description for HIOS, which is largely due
      to two issues: (i) the self-interaction of the electrons with themselves arising
      from the Hartree term of the total energy that is not fully compensated in
      approximate exchange-correlation functionals, and (ii) the lack of long-range
      part of the ubiquitous van der Waals (vdW) interactions. The self-interaction
      errors sometimes lead to incorrect description of charge transfer and electronic
      level alignment in HIOS, although for molecules adsorbed on metals these effects
      will often cancel out in total energy differences. Regarding vdW interactions,
      several promising vdW-inclusive DFT-based methods have been recently demonstrated
      to yield remarkable accuracy for intermolecular interactions in the gas phase.
      However, the majority of these approaches neglect the nonlocal collective
      electron response in the vdW energy tail, an effect that is particularly strong
      in condensed phases and at interfaces between different materials. Here we show
      that the recently developed DFT+vdW(surf) method that accurately accounts for the
      collective electronic response effects enables reliable modeling of structure and
      stability for a broad class of organic molecules adsorbed on metal surfaces. This
      method was demonstrated to achieve quantitative accuracy for aromatic
      hydrocarbons (benzene, naphthalene, anthracene, and diindenoperylene), C60, and
      sulfur/oxygen-containing molecules (thiophene, NTCDA, and PTCDA) on close-packed
      and stepped metal surfaces, leading to an overall accuracy of 0.1 A in adsorption
      heights and 0.1 eV in binding energies with respect to state-of-the-art
      experiments. An unexpected finding is that vdW interactions contribute more to
      the binding of strongly bound molecules on transition-metal surfaces than for
      molecules physisorbed on coinage metals. The accurate inclusion of vdW
      interactions also significantly improves tilting angles and adsorption heights
      for all the studied molecules, and can qualitatively change the potential-energy
      surface for adsorbed molecules with flexible functional groups. Activation
      barriers for molecular switches and reaction precursors are modified as well.

PMID- 24915495
TI  - Do multiple ureteroscopies alter long-term renal function? A study using
      estimated glomerular filtration rate.
AB  - BACKGROUND AND PURPOSE: Although considered standard of care for symptomatic
      urolithiasis, few data are available that evaluate the effects of multiple
      ureteroscopies (URS) with laser lithotripsies on long-term renal function. We
      investigated this relationship in a population with preexisting mild to moderate
      kidney disease. Previous studies have been limited by estimates of glomerular
      filtration rate (eGFR) calculated from creatinine level during acute stone
      obstruction, and inclusion of patients with a history of other stone procedures,
      such as shockwave lithotripsy (SWL) or percutaneous nephrolithotomy (PCNL).
      METHODS: Charts were reviewed for patients with a baseline eGFR below 90
      mL/min/1.73 m(2) who underwent at least two URS for nephrolithiasis at our
      institution from 2004 to 2012. Patients undergoing SWL or PCNL at any point in
      their history were excluded. A total of 26 patients, with a mean of 2.3+/-0.6 URS
      procedures, were included. The eGFR was recorded at baseline before acute stone
      presentation and surgery, and at the last recorded follow-up visit. Stone
      location, total stone burden, and comorbidities were also recorded. RESULTS: The
      mean eGFR changed from 68.0+/-13.3 to 75.4+/-23.0 mL/min/1.73m(2) (mean increase
      of 10.1+/-25.0%; mean annual increase of 3.8+/-15.3%) over a mean follow-up
      period of 28.1 months (range 5-75 mos). There was no significant difference in
      eGFR change between patients with stones treated in the kidney alone vs the
      ureter and kidney combined (12.1% vs 8.3% mean increase; P=0.74). Age, presence
      of diabetes mellitus or hypertension, baseline creatinine level, total stone
      burden, and number of URS performed were not significantly associated with change
      in eGFR. CONCLUSIONS: Using eGFR measured before acute stone presentation, our
      results suggest that multiple ureteroscopies for stones are not detrimental to
      long-term renal function, even in patients with preexisting stage 2-3 chronic
      kidney disease.

PMID- 24915493
TI  - Transplantation of mesenchymal stem cells recruits trophic macrophages to induce
      pancreatic beta cell regeneration in diabetic mice.
AB  - Alleviation of hyperglycemia in chemical-induced diabetic mice has been reported
      after bone marrow transplantation. Nevertheless, the underlying mechanism remains
      elusive. In the present study, we transplanted genetically labeled primary mouse
      mesenchymal stem cells into the pancreas of the streptozotocin-treated
      hyperglycemic isogeneic mice, resulting in a decrease in blood glucose due to a
      recovery in beta cell mass. Further analysis revealed that the increase in beta
      cell mass was predominantly attributable to beta cell replication. The grafted
      mesenchymal stem cells did not transdifferentiate into beta cells themselves but
      recruited and polarized macrophages in a Stromal cell-derived factor 1-dependent
      manner, which in turn promoted beta cell replication. Our finding thus suggests
      that transplantation of autogenic mesenchymal stem cells may increase functional
      beta cell mass by boosting beta cell replication in diabetes. 

PMID- 24915496
TI  - Increased tumour marker concentrations in patients with pericardial effusion with
      anti-inflammatory treatment.

PMID- 24915497
TI  - Size and phase control of cubic lyotropic liquid crystal nanoparticles.
AB  - The effective use of lyotropic liquid crystalline dispersions, such as cubosomes,
      as drug delivery vehicles requires that they have tailored physical
      characteristics that suit specific therapeutics and external conditions. Here, we
      have developed phytantriol-based cubosomes from a dispersion of unilamellar
      vesicles and show that we can control their size as well as the critical packing
      parameter (CPP) of the amphiphilic bilayer through regulation of temperature and
      salt concentration, respectively. Using the anionic biological lipid 1,2-dipalmi
      toylphosphatidylserine (DPPS) to prevent the cubic phase from forming, we show
      that the addition of phosphate buffered saline (PBS) results in a transition from
      small unilamellar vesicles to the cubic phase due to charge-shielding of the
      anionic lipid. Using dynamic light scattering, we show that the cubosomes formed
      following the addition of PBS are as small as 30 nm; however, we can increase the
      average size of the cubsosomes to create an almost monodisperse dispersion of
      cubosomes through cooling. We propose that this phenomenon is brought about
      through the phase separation of the Pluronic F-127 used to stabilize the
      cubosomes. To complement previous work using the salt-induced method of cubosome
      production, we show, using synchrotron small-angle X-ray scattering (SAXS), that
      we can control the CPP of the amphiphile bilayer which grants us phase and
      lattice parameter control of the cubosomes. 

PMID- 24915499
TI  - A study on Zr-Ir multiple bonding active for C-H bond cleavage.
AB  - Zr-Ir hydrido complexes with ansa-(cyclopentadienyl)(amide) as the supporting
      ligand in the zirconium fragment, e.g., (L(1)ZrR)(Cp*Ir)(MU-H)3 [L(1) =
      Me2Si(eta(5)-C5Me4)(N(t)Bu), R = Cl (5), Ph (7), Me (10), alkyl, and aryl] were
      designed, synthesized, and isolated as tractable early-late heterodinuclear
      complexes. Despite the presence of the three supporting hydride ligands, Zr-Ir
      distances in the crystal structures of 5, alkyl, and aryl complexes [2.74-2.76 A]
      were slightly longer than the sum of the element radii of Zr and Ir [2.719 A].
      These hydrocarbyl complexes displayed the thermolytic C-H activation of a variety
      of aromatic compounds and several organometallic compounds. Also, the substrate
      scope and limitation in the Zr-Ir system were studied. The regiochemical outcomes
      during the C-H activation of pyridine derivatives and methoxyarenes suggested the
      in situ generation of a Lewis acidic active intermediate, i.e., (L(1)Zr)(Cp*IrH2)
      (III). The existence of III and relevant sigma-complex intermediates
      {L(1)Zr(eta(2)-R-H)}(Cp*IrH2) (IIR) (R = Me, Ph) in the ligand exchange was
      demonstrated by the direct isolation of a Et3PO-adduct of III (39b) from 7 and
      kinetic studies. The structure of the direct Zr-Ir bonds in IIPh, IIMe, III, and
      39b were probed using computational studies. The unprecedented strong M-M'
      interactions in the early-late heterobimetallic (ELHB) complexes have been
      proposed herein. 

PMID- 24915498
TI  - Stereoselective formation of trisubstituted vinyl boronate esters by the acid
      mediated elimination of alpha-hydroxyboronate esters.
AB  - The copper-catalyzed diboration of ketones followed by an acid-catalyzed
      elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl
      boronate esters with moderate to good yields and selectivity. Addition of tosic
      acid to the crude diboration products provides the corresponding vinyl boronate
      esters upon elimination. The trisubstituted vinyl boronate esters are formed as
      the (Z)-olefin isomer, which was established by subjecting the products to a
      Suzuki-Miyaura coupling reaction to obtain alkenes of known geometry. 

PMID- 24915500
TI  - Dose or content? Effectiveness of pain rehabilitation programs for patients with
      chronic low back pain: A systematic review. Waterschoot et al., Pain 155 (2014)
      179-189.

PMID- 24915501
TI  - Prevalence and mechanism of polyunsaturated aldehydes production in the green
      tide forming macroalgal genus Ulva (Ulvales, Chlorophyta).
AB  - Lipoxygenase/hydroperoxide lyase mediated transformations convert polyunsaturated
      fatty acids into various oxylipins. First, lipoxygenases catalyze fatty acid
      oxidation to fatty acid hydroperoxides. Subsequently, breakdown reactions result
      in a wide array of metabolites with multiple physiological and ecological
      functions. These fatty acid transformations are highly diverse in marine algae
      and play a crucial rule in e.g., signaling, chemical defense, and stress response
      often mediated through polyunsaturated aldehydes (PUAs). In this study, green
      tide-forming macroalgae of the genius Ulva (Chlorophyta) were collected at
      various sampling sites in the lagoon of the Ria Formosa (Portugal) and were
      surveyed for PUAs. We demonstrated that sea-lettuce like but not tube-like
      morphotypes produce elevated amounts of volatile C10-polyunsaturated aldehydes
      (2,4,7-decatrienal and 2,4-decadienal) upon tissue damage. Moreover,
      morphogenetic and phylogenetic analyses of the collected Ulva species revealed
      chemotaxonomic significance of the perspective biosynthetic pathways. The
      aldehydes are derived from omega-3 and omega-6 polyunsaturated fatty acids (PUFA)
      with 20 or 18 carbon atoms including eicosapentaenoic acid (C20:5 n-3),
      arachidonic acid (C20:4 n-6), stearidonic acid (C18:4 n-3), and gamma-linolenic
      acid (C18:3 n-6). We present first evidences that lipoxygenase-mediated (11-LOX
      and 9-LOX) eicosanoid and octadecanoid pathways catalyze the transformation of
      C20- and C18-polyunsaturated fatty acids into PUAs and concomitantly into short
      chain hydroxylated fatty acids. 

PMID- 24915503
TI  - Dynamics of the ClpP serine protease: a model for self-compartmentalized
      proteases.
AB  - ClpP is a highly conserved serine protease present in most bacterial species and
      in the mitochondria of mammalian cells. It forms a cylindrical tetradecameric
      complex arranged into two stacked heptamers. The two heptameric rings of ClpP
      enclose a roughly spherical proteolytic chamber of about 51 A in diameter with 14
      Ser-His-Asp proteolytic active sites. ClpP typically forms complexes with
      unfoldase chaperones of the AAA+ superfamily. Chaperones dock on one or both ends
      of the ClpP double ring cylindrical structure. Dynamics in the ClpP structure is
      critical for its function. Polypeptides targeted for degradation by ClpP are
      initially recognized by the AAA+ chaperones. Polypeptides are unfolded by the
      chaperones and then translocated through the ClpP axial pores, present on both
      ends of the ClpP cylinder, into the ClpP catalytic chamber. The axial pores of
      ClpP are gated by dynamic axial loops that restrict or allow substrate entry. As
      a processive protease, ClpP degrades substrates to generate peptides of about 7-8
      residues. Based on structural, biochemical and theoretical studies, the exit of
      these polypeptides from the proteolytic chamber is proposed to be mediated by the
      dynamics of the ClpP oligomer. The ClpP cylinder has been found to exist in at
      least three conformations, extended, compact and compressed, that seem to
      represent different states of ClpP during its proteolytic functional cycle. In
      this review, we discuss the link between ClpP dynamics and its activity. We
      propose that such dynamics also exist in other cylindrical proteases such as HslV
      and the proteasome.

PMID- 24915504
TI  - Glycosylation-mediated targeting of carriers.
AB  - For safe and effective therapy, drugs should be delivered selectively to their
      target tissues or cells at an optimal rate. Drug delivery system technology
      maximizes the therapeutic efficacy and minimizes unfavorable drug actions by
      controlling their distribution profiles. Ligand-receptor binding is a typical
      example of specific recognition mechanisms in the body; therefore, ligand
      modified drug carriers have been developed for active targeting based on receptor
      mediated endocytosis. Among the various ligands reported thus far, sugar
      recognition is a promising approach for active targeting because of their high
      affinity and expression. Glycosylation has been applied for both macromolecular
      and liposomal carriers for cell-selective drug targeting. Recently, the
      combination of ultrasound exposure and glycosylated bubble liposomes has been
      developed. In this review, recent advances of glycosylation-mediated targeted
      drug delivery systems are discussed. 

PMID- 24915505
TI  - FLAMEnGO 2.0: an enhanced fuzzy logic algorithm for structure-based assignment of
      methyl group resonances.
AB  - We present an enhanced version of the FLAMEnGO (Fuzzy Logic Assignment of Methyl
      Group) software, a structure-based method to assign methyl group resonances in
      large proteins. FLAMEnGO utilizes a fuzzy logic algorithm coupled with Monte
      Carlo sampling to obtain a probability-based assignment of the methyl group
      resonances. As an input, FLAMEnGO requires either the protein X-ray structure or
      an NMR structural ensemble including data such as methyl-methyl NOESY,
      paramagnetic relaxation enhancement (PRE), methine-methyl TOCSY data. Version 2.0
      of this software (FLAMEnGO 2.0) has a user-friendly graphic interface and
      presents improved modules that enable the input of partial assignments and
      additional NMR restraints. We tested the performance of FLAMEnGO 2.0 on maltose
      binding protein (MBP) as well as the C-subunit of the cAMP-dependent protein
      kinase A (PKA-C). FLAMEnGO 2.0 can be used as a standalone method or to assist in
      the completion of partial resonance assignments and can be downloaded at
      www.chem.umn.edu/groups/veglia/forms/flamengo2-form.html. 

PMID- 24915506
TI  - Reducing the discharge of micropollutants in the aquatic environment: the
      benefits of upgrading wastewater treatment plants.
AB  - Micropollutants (MPs) as individual compounds or in complex mixtures are relevant
      for water quality and may trigger unwanted ecological effects. MPs originate from
      different point and diffuse sources and enter water bodies via different flow
      paths. Effluents from conventional wastewater treatment plants (WWTPs), in which
      various MPs are not or not completely removed, is one major source. To improve
      the water quality and avoid potential negative ecological effects by
      micropollutants, various measures to reduce the discharge should be taken. In
      this feature we discuss one of these measures; the benefits of upgrading WWTPs
      toward reduced MP loads and toxicities from wastewater effluents, using the
      recently decided Swiss strategy as an example. Based on (i) full-scale case
      studies using ozonation or powder activated carbon treatment, showing substantial
      reduction of MP discharges and concomitant reduced toxicities, (ii) social and
      political acceptance, (iii) technical feasibility and sufficient cost
      effectiveness, the Swiss authorities recently decided to implement additional
      wastewater treatment steps as mitigation strategy to improve water quality. Since
      MPs are of growing global concern, the concepts and considerations behind the
      Swiss strategy are explained in this feature, which could be of use for other
      countries as well. It should be realized that upgrading WWTPs is not the only
      solution to reduce the discharge of MPs entering the environment, but is part of
      a broader, multipronged mitigation strategy. 

PMID- 24915507
TI  - Understanding the impact of the Women's Health Initiative.

PMID- 24915508
TI  - Genetic predisposition to ovotoxic effects of smoking may hasten time to
      menopause.

PMID- 24915502
TI  - The cell envelope glycoconjugates of Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) remains the second most common cause of death due to a single
      infectious agent. The cell envelope of Mycobacterium tuberculosis (Mtb), the
      causative agent of the disease in humans, is a source of unique glycoconjugates
      and the most distinctive feature of the biology of this organism. It is the basis
      of much of Mtb pathogenesis and one of the major causes of its intrinsic
      resistance to chemotherapeutic agents. At the same time, the unique structures of
      Mtb cell envelope glycoconjugates, their antigenicity and essentiality for
      mycobacterial growth provide opportunities for drug, vaccine, diagnostic and
      biomarker development, as clearly illustrated by recent advances in all of these
      translational aspects. This review focuses on our current understanding of the
      structure and biogenesis of Mtb glycoconjugates with particular emphasis on one
      of the most intriguing and least understood aspect of the physiology of
      mycobacteria: the translocation of these complex macromolecules across the
      different layers of the cell envelope. It further reviews the rather impressive
      progress made in the last 10 years in the discovery and development of novel
      inhibitors targeting their biogenesis.

PMID- 24915509
TI  - Letter to the editor.

PMID- 24915510
TI  - The economic burden of self-reported and undiagnosed cardiovascular diseases and
      diabetes on Indonesian households.
AB  - OBJECTIVES: The goal of this study is: (1) to estimate the current direct out-of
      pocket (OOP) and indirect non-communicable diseases (NCD) burden on Indonesian
      households and (2) to project NCD prevalence and burden in 2020 focusing
      specifically on hypertension, diabetes, heart problems and stroke. METHODS: This
      study relies on econometric analyses based on four waves of the Indonesian Family
      Life Survey (IFLS). RESULTS: In aggregate, of the NCDs studied, heart problems
      exert the greatest economic burden on households, costing Int$1.56 billion in OOP
      and indirect burden in 2010. This was followed by hypertension (Int$1.36
      billion), diabetes (Int$0.81 billion) and stroke (Int$0.29 billion). The OOP and
      indirect burden of these conditions is estimated to be Int$4.02 billion. Diabetes
      and stroke are expected to have the largest proportional increases in burden by
      2020; 56.0% for diabetes and 56.9% for stroke to total Int$1.27 billion and
      Int$0.45 billion respectively. The burden of heart problems in 2020 is expected
      to increase by 34.4% to total Int$2.09 billion and hypertension burden will
      increase by 46.1% to Int$1.99 billion. In 2020, these conditions are expected to
      impose an economic burden of Int$5.80 billion. CONCLUSION: In conclusion, this
      study demonstrates the significant burden of 4 primary NCDs on Indonesian
      households. In addition to the indirect burden, hypertension, diabetes, heart
      problems and stroke account for 8% of the nation's OOP healthcare expenditure,
      and due to rising disease prevalence and an aging population, this figure is
      expected to increase to 12% by 2020 without a significant health intervention.

PMID- 24915513
TI  - Truncated outlier filtering.
AB  - The statistical analysis of data can be heavily influenced by measurements of
      extreme value. If such measurements are contained in the remote tail ends of the
      true population distribution from which they are drawn, they are referred to as
      outliers. Neglecting to filter outliers from a sample can distort statistical
      computations and result in faulty conclusions. Conventional techniques identify
      measurements, whose distances from the mean exceed a selected multiple of the
      sample standard deviation, as outliers. Such approaches, however, can fail to
      classify measurements with large normalized distances as outliers. The truncated
      outlier filtering method first replaces the minimum and maximum of the population
      before computing the exclusion criterion. This mitigates the influence of
      abnormally large (or small) measurements on the normalized distance and hence
      yields a more compact criterion for outlier determination. Moreover, the method
      generalizes to two or more dimensions. Simulated one-dimensional and
      multidimensional data are analyzed. A discussion of the results is also
      presented. 

PMID- 24915511
TI  - In cellulo evaluation of phototransformation quantum yields in fluorescent
      proteins used as markers for single-molecule localization microscopy.
AB  - Single-molecule localization microscopy of biological samples requires a precise
      knowledge of the employed fluorescent labels. Photoactivation, photoblinking and
      photobleaching of phototransformable fluorescent proteins influence the data
      acquisition and data processing strategies to be used in (Fluorescence)
      Photoactivation Localization Microscopy ((F)-PALM), notably for reliable
      molecular counting. As these parameters might depend on the local environment,
      they should be measured in cellulo in biologically relevant experimental
      conditions. Here, we measured phototransformation quantum yields for Dendra2
      fused to actin in fixed mammalian cells in typical (F)-PALM experiments. To this
      aim, we developed a data processing strategy based on the clustering optimization
      procedure proposed by Lee et al (PNAS 109, 17436-17441, 2012). Using simulations,
      we estimated the range of experimental parameters (molecular density, molecular
      orientation, background level, laser power, frametime) adequate for an accurate
      determination of the phototransformation yields. Under illumination at 561 nm in
      PBS buffer at pH 7.4, the photobleaching yield of Dendra2 fused to actin was
      measured to be (2.5 +/- 0.4) * 10(-5), whereas the blinking-off yield and
      thermally-activated blinking-on rate were measured to be (2.3 +/- 0.2) * 10(-5)
      and 11.7 +/- 0.5 s-1, respectively. These phototransformation yields differed
      from those measured in poly-vinyl alcohol (PVA) and were strongly affected by
      addition of the antifading agent 1,4-diazabicyclo[2.2.2]octane (DABCO). In the
      presence of DABCO, the photobleaching yield was reduced 2-fold, the blinking-off
      yield was decreased more than 3-fold, and the blinking-on rate was increased 2
      fold. Therefore, DABCO largely improved Dendra2 photostability in fixed mammalian
      cells. These findings are consistent with redox-based bleaching and blinking
      mechanisms under (F)-PALM experimental conditions. Finally, the green-to-red
      photoconversion quantum yield of Dendra2 was estimated to be (1.4 +/- 0.6) * 10(
      5) in cellulo under 405 nm illumination.

PMID- 24915512
TI  - Structural complexity in metal-organic frameworks: simultaneous modification of
      open metal sites and hierarchical porosity by systematic doping with defective
      linkers.
AB  - A series of defect-engineered metal-organic frameworks (DEMOFs) derived from
      parent microporous MOFs was obtained by systematic doping with defective linkers
      during synthesis, leading to the simultaneous and controllable modification of
      coordinatively unsaturated metal sites (CUS) and introduction of functionalized
      mesopores. These materials were investigated via temperature-dependent
      adsorption/desorption of CO monitored by FTIR spectroscopy under ultra-high
      vacuum conditions. Accurate structural models for the generated point defects at
      CUS were deduced by matching experimental data with theoretical simulation. The
      results reveal multivariate diversity of electronic and steric properties at CUS,
      demonstrating the MOF defect structure modulation at two length scales in a
      single step to overcome restricted active site specificity and confined
      coordination space at CUS. Moreover, the DEMOFs exhibit promising modified
      physical properties, including band gap, magnetism, and porosity, with
      hierarchical micro/mesopore structures correlated with the nature and the degree
      of defective linker incorporation into the framework. 

PMID- 24915514
TI  - Catalytic functionalization of tertiary alcohols to fully substituted carbon
      centres.
AB  - The catalytic nucleophilic substitution of tertiary alcohols using carbon or
      heteroatom based nucleophiles is a versatile methodology for the efficient,
      diverse and atom economical construction of fully substituted carbon centres,
      including both quaternary carbons and heteroatom substituted tetrasubstituted
      carbons, which only produces water as the by-product. This review summarizes the
      recent progress in this field, including the catalytic asymmetric studies and
      their application in the natural product synthesis, briefly discusses the
      reaction mechanism and challenges, and outlines synthetic opportunities that are
      still open. 

PMID- 24915515
TI  - Footedness across ages: distinction between mobilization and stabilization tasks.
AB  - Foot preference was assessed in 5- to 20-year-old participants separately for
      mobilization and stabilization task categories through observation of
      performance. Results revealed different laterality profiles of pedal preference
      between task categories. Interindividual consistency and strong preference for
      the right foot in mobilization tasks contrasted to large interindividual
      variability and weak pedal preference in stabilization tasks. Strength of pedal
      preference for each task category was stable across age groups. These findings
      suggest that daily living experiences over years of use do not modify the
      footedness profile observed in childhood. 

PMID- 24915516
TI  - Cu(I) and Ag(I) complexes of 7,10-bis-N-heterocycle-diazafluoranthenes:
      programmed molecular grids?
AB  - Reactions of 7,10-disubstituted diazafluoranthene derivatives with three
      different silver(I) salts AgX (X = [PF6](-), [SbF6](-), [CB11HCl11](-)) and
      [Cu(CH3CN)4]PF6 afforded complexes exhibiting five different motifs. The crystal
      structures of the free ligands and nine new complexes from this series of
      reactions are reported. The use of 2,5-di-tert-butyl-7,10-di(pyridin-2-yl)-8,9
      diazafluoranthene as a ligand leads to the formation of the tetranuclear
      compounds [Ag4(C32H30N4)4][PF6]4.3C6H6.4MeCN, [Ag4(C32H30N4)4][SbF6]4.4C5H12 and
      [Cu4(C32H30N4)4][PF6]4.8C3H6O, which exhibit "propeller" and saddle-type
      geometry, respectively, as well as a dinuclear complex
      [Ag2(C32H30N4)2][CHB11Cl11]2.4C6H4Cl2.CH2Cl2. The reactions involving the less
      sterically hindered 2,5-di-tert-butyl-7,10-di-(pyrimidin-2-yl)-8,9
      diazafluoranthene and 2,5-di-tert-butyl-7,10-di(thiazol-2-yl)-8,9
      diazafluoranthene afforded crystals of the dinuclear complexes
      [Ag2(C30H28N6)2][PF6]2.0.5CH2Cl2.0.5C6H5Cl.0.5C6H12,
      [Ag2(C30H28N6)2][SbF6]2.C3H6O.0.5C6H14.0.5C6H6, the polymeric species
      [Ag2(C28H26N4S2)2]n.2n[PF6]n.nC3H6O and the tetranuclear compounds
      [Cu4(C26H25N4S2)4][PF6]4.2CHCl3.2C3H6O and [Cu4(C30H28N6)4][PF6]4.2.17H2O, which
      possess saddle and grid-like architectures, respectively. Conformational analysis
      of the free ligands showed that they exhibit N-C-C-N torsion angles ranging from
      syn clinal (58 degrees ) to fully anti-periplanar conformations; the syn clinal
      conformation dominates in the complexes. The relative energies of the possible
      structural conformations of the synthesized ligands, as well as of oxazole
      disubstituted diazafluoranthenes, were calculated using density functional theory
      at the B97D/Def2-TZVPP level of theory.

PMID- 24915517
TI  - Insulin regulates monocyte trans-endothelial migration through surface expression
      of macrophage-1 antigen.
AB  - During the pathogenesis of atherosclerosis, adhesion of monocytes to vascular
      endothelium and subsequent migration across the endothelium has been recognized
      as a key process in the chronic inflammatory response in atherosclerosis. As type
      2 diabetes is closely associated with the pathogenesis of atherosclerosis, we
      investigated whether monocyte adhesion and migration were affected by insulin. We
      found that insulin activated Akt and induced subsequent migration in THP-1.
      However, glucose and insulin-like growth factor-1, which is a growth factor that
      is structurally similar to insulin, were not effective. Insulin-dependent
      migration of THP-1 was blocked by inhibition of PI3K or Akt and by silencing of
      Akt1. Insulin-dependent migration of bone marrow-derived monocytic cells (BDMCs)
      was attenuated by inhibition of PI3K and Akt. In addition, BDMCs from Akt1(-/-)
      mice showed defects in insulin-dependent migration. Stimulation of THP-1 with
      insulin caused adhesion with human vein endothelial cells (HUVECs) that was
      blocked by silencing of Akt1. However, stimulation of HUVECs did not cause
      adhesion with THP-1. Moreover, BDMCs from Akt1(-/-) mice showed defects in
      insulin-dependent adhesion with HUVECs. Insulin induced surface expression of Mac
      1, and neutralization of Mac-1 blocked insulin-induced adhesion of THP-1 as well
      as BDMCs. Surface expression of Mac-1 was blocked in THP-1 with silenced Akt1,
      and in BDMCs isolated from mice lacking Akt1. Finally, trans-endothelial
      migration of THP-1 and BDMCs was blocked by Mac-1-neutralizing antibody, in THP-1
      with silenced Akt1 and in BDMCs from Akt1(-/-) mice. These results suggest that
      insulin stimulates monocyte trans-endothelial migration through Akt-dependent
      surface expression of Mac-1, which may be part of the atherogenesis in type 2
      diabetes. 

PMID- 24915519
TI  - Ammonium carbonate is more attractive than apple and hawthorn fruit volatile
      lures to Rhagoletis pomonella (Diptera: Tephritidae) in Washington State.
AB  - The apple maggot fly, Rhagoletis pomonella (Walsh), is an introduced, quarantine
      pest of apple (Malus domestica Borkhausen) in the Pacific Northwest of the United
      States. In the eastern United States where the fly is native, fruit volatiles
      have been reported to be more attractive than ammonia compounds to R. pomonella.
      However, the opposite may be true in the western United States. Here, we
      determined whether newly identified western apple and western hawthorn fruit
      volatiles are more attractive than ammonium carbonate (AC) to R. pomonella in
      apple, black hawthorn, and ornamental hawthorn trees in western Washington State.
      In all three host trees, sticky red sphere or yellow panel traps baited with AC
      generally caught more flies than traps baited with lures containing the four
      newly developed fruit blends (modified eastern apple, western apple, western
      ornamental hawthorn, and western black hawthorn) or two older blends (eastern
      apple and eastern downy hawthorn). Fruit volatiles also displayed more variation
      among trapping studies conducted at different sites, in different host trees, and
      across years than AC. The results imply that traps baited with AC represent the
      best approach to monitoring R. pomonella in Washington State. 

PMID- 24915518
TI  - Myocardial ischemic reperfusion induces de novo Nrf2 protein translation.
AB  - Nrf2 is a bZIP transcription factor regulating the expression of antioxidant and
      detoxification genes. We have found that Nrf2 knockout mice have an increased
      infarction size in response to regional ischemic reperfusion and have a reduced
      degree of cardiac protection by means of ischemic preconditioning. With cycles of
      brief ischemia and reperfusion (5'I/5'R) that induce cardiac protection in wild
      type mice, an elevated Nrf2 protein was observed without prior increases of Nrf2
      mRNA. When an mRNA species is being translated into a protein, it is occupied by
      multiple ribosomes. The level of ribosome-associated Nrf2 mRNA increased
      following cycles of 5'I/5'R, supporting de novo Nrf2 protein translation. A
      dicistronic reporter assay indicated a role of the 5' untranslated region (5'
      UTR) of Nrf2 mRNA in oxidative stress induced Nrf2 protein translation in
      isolated cardiomyocytes. Western blot analyses after isolation of proteins
      binding to biotinylated Nrf2 5' UTR from the myocardium or cultured
      cardiomyocytes demonstrated that cycles of 5'I/5'R or oxidants caused an
      increased association of La protein with Nrf2 5' UTR. Ribonucleoprotein complex
      immunoprecipitation assays confirmed such association indeed occurring in vivo.
      Knocking down La using siRNA was able to prevent Nrf2 protein elevation by
      oxidants in cultured cardiomyocytes and by cycles of 5'I/5'R in the myocardium.
      Our data point out a novel mechanism of cardiac protection by de novo Nrf2
      protein translation involving interaction of La protein with 5' UTR of Nrf2 mRNA
      in cardiomyocytes. 

PMID- 24915520
TI  - Perk gene dosage regulates glucose homeostasis by modulating pancreatic beta-cell
      functions.
AB  - BACKGROUND: Insulin synthesis and cell proliferation are under tight regulation
      in pancreatic beta-cells to maintain glucose homeostasis. Dysfunction in either
      aspect leads to development of diabetes. PERK (EIF2AK3) loss of function
      mutations in humans and mice exhibit permanent neonatal diabetes that is
      characterized by insufficient beta-cell mass and reduced proinsulin trafficking
      and insulin secretion. Unexpectedly, we found that Perk heterozygous mice
      displayed lower blood glucose levels. METHODOLOGY: Longitudinal studies were
      conducted to assess serum glucose and insulin, intracellular insulin synthesis
      and storage, insulin secretion, and beta-cell proliferation in Perk heterozygous
      mice. In addition, modulation of Perk dosage specifically in beta-cells showed
      that the glucose homeostasis phenotype of Perk heterozygous mice is determined by
      reduced expression of PERK in the beta-cells. PRINCIPAL FINDINGS: We found that
      Perk heterozygous mice first exhibited enhanced insulin synthesis and secretion
      during neonatal and juvenile development followed by enhanced beta-cell
      proliferation and a substantial increase in beta-cell mass at the adult stage.
      These differences are not likely to entail the well-known function of PERK to
      regulate the ER stress response in cultured cells as several markers for ER
      stress were not differentially expressed in Perk heterozygous mice. CONCLUSIONS:
      In addition to the essential functions of PERK in beta-cells as revealed by
      severely diabetic phenotype in humans and mice completely deficient for PERK,
      reducing Perk gene expression by half showed that intermediate levels of PERK
      have a profound impact on beta-cell functions and glucose homeostasis. These
      results suggest that an optimal level of PERK expression is necessary to balance
      several parameters of beta-cell function and growth in order to achieve
      normoglycemia.

PMID- 24915522
TI  - Detecting deep divergence in seventeen populations of tea geometrid (Ectropis
      obliqua Prout) in China by COI mtDNA and cross-breeding.
AB  - The tea geometrid (Ectropis obliqua Prout, Lepidoptera: Geometridae) is a
      dominant chewing insect endemic in most tea-growing areas in China. Recently some
      E. obliqua populations have been found to be resistant to the
      nucleopolyhedrovirus (EoNPV), a host-specific virus that has so far been found
      only in E. obliqua. Although the resistant populations are morphologically
      indistinguishable from susceptible populations, we conducted a nationwide
      collection and examined the genetic divergence in the COI region of the mtDNA in
      E. obliqua. Phylogenetic analyses of mtDNA in 17 populations revealed two
      divergent clades with genetic distance greater than 3.7% between clades and less
      than 0.7% within clades. Therefore, we suggest that E. obliqua falls into two
      distinct groups. Further inheritance analyses using reciprocal single-pair mating
      showed an abnormal F1 generation with an unbalanced sex ratio and the inability
      to produce fertile eggs (or any eggs) through F1 self-crossing. These data
      revealed a potential cryptic species complex with deep divergence and
      reproductive isolation within E. obliqua. Uneven distribution of the groups
      suggests a possible geographic effect on the divergence. Future investigations
      will be conducted to examine whether EoNPV selection or other factors prompted
      the evolution of resistance.

PMID- 24915523
TI  - Two adjacent and similar TetR family transcriptional regulator genes, SAV577 and
      SAV576, co-regulate avermectin production in Streptomyces avermitilis.
AB  - Streptomyces avermitilis is an important bacterial species used for industrial
      production of avermectins, a family of broad-spectrum anthelmintic agents. We
      previously identified the protein SAV576, a TetR family transcriptional regulator
      (TFR), as a downregulator of avermectin biosynthesis that acts by controlling
      transcription of its major target gene SAV575 (which encodes cytochrome
      P450/NADPH-ferrihemoprotein reductase) and ave genes. SAV577, another TFR gene,
      encodes a SAV577 protein that displays high amino acid homology with SAV576. In
      this study, we examined the effect of SAV577 on avermectin production and the
      relationships between SAV576 and SAV577. SAV577 downregulated avermectin
      biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly
      repressed SAV575 transcription, and reciprocally repressed each other's
      expression. SAV575 transcription levels in various S. avermitilis strains were
      correlated with avermectin production levels. DNase I footprinting and
      electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete
      for the same binding regions, and that DNA-binding affinity of SAV576 is much
      stronger than that of SAV577. GST pull-down assays revealed no direct interaction
      between the two proteins. Taken together, these findings suggest that SAV577
      regulates avermectin production in S. avermitilis by a mechanism similar to that
      of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is
      the first report of two adjacent and similar TFR genes that co-regulate
      antibiotic production in Streptomyces. 

PMID- 24915526
TI  - Impairments in facial affect recognition associated with autism spectrum
      disorders: a meta-analysis.
AB  - Autism spectrum disorders (ASDs) are characterized by social impairments,
      including inappropriate responses to affective stimuli and nonverbal cues, which
      may extend to poor face-emotion recognition. However, the results of empirical
      studies of face-emotion recognition in individuals with ASD have yielded
      inconsistent findings that occlude understanding the role of face-emotion
      recognition deficits in the development of ASD. The goal of this meta-analysis
      was to address three as-yet unanswered questions. Are ASDs associated with
      consistent face-emotion recognition deficits? Do deficits generalize across
      multiple emotional expressions or are they limited to specific emotions? Do age
      or cognitive intelligence affect the magnitude of identified deficits? The
      results indicate that ASDs are associated with face-emotion recognition deficits
      across multiple expressions and that the magnitude of these deficits increases
      with age and cannot be accounted for by intelligence. These findings suggest
      that, whereas neurodevelopmental processes and social experience produce
      improvements in general face-emotion recognition abilities over time during
      typical development, children with ASD may experience disruptions in these
      processes, which suggested distributed functional impairment in the neural
      architecture that subserves face-emotion processing, an effect with downstream
      developmental consequences. 

PMID- 24915525
TI  - Validity and reliability of the TGMD-2 for South Korean children.
AB  - The purpose of this study was to investigate the reliability and validity of the
      Test of Gross Motor Development-2 (TGMD-2) for South Korean children. Three
      professionals assessed all children. Appropriate internal consistency (Cronbach's
      alpha values from 0.73 to 0.87), concordance among evaluators (>= .92), and test
      retest reliability (locomotor = .91; object control = .85) were found.
      Appropriate fit indexes were found for the 1-factor nested model and the 2-factor
      model (goodness-of-fit index = 0.91, normed fit index = 0.87, comparative fit
      index = 0.94, Tucker-Lewis index = 0.93, incremental fit index = 0.95, root mean
      square error of approximation = 0.07). The 2-factor results from South Korean
      sample were similar to the results reported in the American sample. The TGMD-2 is
      an appropriate tool for assessing the motor skills of children in South Korea.

PMID- 24915527
TI  - Quantifying the role of anion-pi interactions in anion-pi catalysis.
AB  - Matile et al. introduced the concept of anion-pi catalysis [Angew. Chem., Int.
      Ed. 2013, 52, 9940; J. Am. Chem. Soc. 2014, 136, 2101], reporting naphthalene
      diimide (NDI)-based organocatalysts for the Kemp elimination reaction. We report
      computational analyses of the operative noncovalent interactions, revealing that
      anion-pi interactions actually increase the activation barriers for some of these
      catalyzed reactions. We propose new catalysts that are predicted to achieve
      significant lowering of the activation energy through anion-pi interactions. 

PMID- 24915524
TI  - The interaction between amyloid-beta peptides and anionic lipid membranes
      containing cholesterol and melatonin.
AB  - One of the hallmarks of Alzheimer's disease is the formation of senile plaques,
      primarily consisting of amyloid-beta (Abeta) peptides. Peptide-membrane and
      peptide-lipid interactions are thought to be crucial in this process. We studied
      the interaction of Abeta1-42 and Abeta25-35 peptides with anionic lipid membranes
      made of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphoserine (DMPS)
      using X-ray diffraction. We compare the experimentally determined electron
      densities in the gel state of the membranes with density calculations from
      peptide structures reported in the Protein Data Bank in order to determine the
      position of the peptide in the bilayers. The full length peptide Abeta1-42 was
      found to embed in the hydrocarbon core of the anionic lipid bilayers. Two
      populations were found for the Abeta25-35 peptide: (1) membrane-bound states in
      the hydrophilic head group region of the bilayers, where the peptides align
      parallel to the membranes, and (2) an embedded state in the bilayer center. Aging
      plays an important role in the development of Alzheimer's, in particular with
      respect to changes in cholesterol and melatonin levels in the brain tissue.
      Immiscible cholesterol plaques were created by addition of 30 mol% cholesterol to
      the anionic membranes. The Abeta25-35 peptides were found to strongly interact
      with the lipid bilayers, displacing further cholesterol molecules into the
      plaques, effectively lowering the cholesterol concentration in the membranes and
      increasing the total fraction of cholesterol plaques. Addition of 30 mol%
      melatonin molecules to the anionic membranes drastically reduced the population
      of the membrane-embedded Abeta state. These results present experimental evidence
      for an interaction between Abeta peptides, melatonin and cholesterol in lipid
      membranes.

PMID- 24915528
TI  - Hearing dummies: individualized computer models of hearing impairment.
AB  - Objective: Our aim was to explore the usage of individualized computer models to
      simulate hearing loss based on detailed psychophysical assessment and to offer
      hypothetical diagnoses of the underlying pathology. DESIGN: Individualized
      computer models of normal and impaired hearing were constructed and evaluated
      using the psychophysical data obtained from human listeners. Computer models of
      impaired hearing were generated to reflect the hypothesized underlying pathology
      (e.g. dead regions, outer hair cell dysfunction, or reductions in endocochlear
      potential). These models were evaluated in terms of their ability to replicate
      the original patient data. STUDY SAMPLE: Auditory profiles were measured for two
      normal and five hearing-impaired listeners using a battery of three
      psychophysical tests (absolute thresholds, frequency selectivity, and
      compression). RESULTS: The individualized computer models were found to match the
      data. Useful fits to the impaired profiles could be obtained by changing only a
      single parameter in the model of normal hearing. Sometimes, however, it was
      necessary to include an additional dead region. CONCLUSION: The creation of
      individualized computer models of hearing loss can be used to simulate auditory
      profiles of impaired listeners and suggest hypotheses concerning the underlying
      peripheral pathology.

PMID- 24915531
TI  - Analytical investigations on elastomeric shells of new Poly Implant Prothese
      (PIP) breast and from sixteen cases of surgical explantation.
AB  - In this study we have analysed the chemical composition of the extractable
      components from the elastomeric shells from n=27 explanted implants (n=16
      patients), n=2 new PIP implants, and from explanted Eurosilicone and McGhan
      implants (n=2 for each brand). Empty elastomeric PIP shells (n=2) were also
      available for analysis. Prostheses were explanted between 2011 and 2012, after 3
      11 years of implantation. Patients presented pre- and post-operation
      complications of different degrees. First we evaluated the micro-structural
      features of the shells by phase contrast microscopy, and compared the results
      with those obtained using attenuated total reflectance infrared spectroscopy (ATR
      FT-IR), head space gas chromatography coupled to mass spectrometry (HS-GC-MS) and
      GC-MS in direct injection mode. The results of these studies confirm and explain
      the conclusion of previous international investigations that evidenced a linear
      decrease of rupture rate for prostheses implanted after 2006. The analytical
      identification of a series of UV sensitive radical photo-initiators (0.1%-0.2%
      w/w), belonging to the benzophenone family, in the shells of new and explanted
      prostheses produced after 2006 (associated with a strong smell absent in those
      produced earlier), in parallel to (ii) the removal of the anti bleed barrier from
      their manufacturing procedure (introduced after 2001), strongly suggested that
      from 2007, the PIP company used a polymerisation process different from that
      declared, probably as a consequence of the first reports of rupture problems. In
      addition, the HS-GC-MS experiments demonstrated that at body temperature the
      diffusivity of low molecular weight (LMW) silicones present in the PIP filler
      silicone is significantly higher than that of LMW silicones in an approved
      implant. 

PMID- 24915530
TI  - HIV associated neurocognitive disorders (HAND) in Malawian adults and effect on
      adherence to combination anti-retroviral therapy: a cross sectional study.
AB  - BACKGROUND: Little is known about the prevalence and burden of HIV associated
      neurocognitive disorder (HAND) among patients on combination antiretroviral
      therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in
      adult Malawians on cART and investigated the relationship between HAND and
      adherence to cART. METHODS: HIV positive adults in Blantyre, Malawi underwent a
      full medical history, neurocognitive test battery, depression score, Karnofsky
      Performance Score and adherence assessment. The Frascati criteria were used to
      diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was
      drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV
      negative adults were recruited from the HIV testing clinic to provide normative
      scores for the neurocognitive battery. RESULTS: One hundred and six HIV positive
      patients, with median (range) age 39 (18-71) years, 73% female and median (range)
      CD4 count 323.5 (68-1039) cells/ul were studied. Symptomatic neurocognitive
      impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV
      associated dementia [HAD]). A further 55% fulfilled Frascati criteria for
      asymptomatic neurocognitive impairment (ANI); however factors other than
      neurocognitive impairment could have confounded this estimate. Neither the
      symptomatic (MND and HAD) nor asymptomatic (ANI) forms of HAND were associated
      with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44
      (CI. 0.234, 8.798; p = 0.696) and aOR 0.577 (CI. 0.09, 3.605; p = 0.556)
      respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a
      GDS of less than 0.6, consistent with normal neurocognition.
      DISCUSSION/CONCLUSION: Fifteen percent of adult Malawians on cART had a diagnosis
      of MND or HAD. Subtherapeutic drug concentrations were found exclusively in
      patients with normal neurocognitive function suggesting HAND did not affect cART
      adherence. Further study of HAND requires more robust locally derived normative
      neurocognitive values and determination of the clinical relevance of ANI.

PMID- 24915532
TI  - Hypoxia imaging endoscopy equipped with laser light source from preclinical live
      animal study to first-in-human subject research.
AB  - A goal in next-generation endoscopy is to develop functional imaging techniques
      to open up new opportunities for cancer diagnosis. Although spatial and temporal
      information on hypoxia is crucial for understanding cancer physiology and
      expected to be useful for cancer diagnosis, existing techniques using fluorescent
      indicators have limitations due to low spatial resolution and invasive
      administration. To overcome these problems, we developed an imaging technology
      based on hemoglobin oxygen saturation in both the tumor and surrounding mucosa
      using a laser endoscope system, and conducted the first human subject research
      for patients with aero-digestive tract cancer. The oxygen saturation map
      overlapped the images of cancerous lesions and indicated highly heterogeneous
      features of oxygen supply in the tumor. The hypoxic region of the tumor surface
      was found in both early cancer and cancer precursors. This technology illustrates
      a novel aspect of cancer biology as a potential biomarker and can be widely
      utilized in cancer diagnosis. 

PMID- 24915534
TI  - Circadian clock and cancer therapy: an unexpected journey.
AB  - Chronotherapy of cancer is one of the oldest examples of the clinical application
      of biological rhythms. Growing understanding of the importance of biological
      timing in physiology and pathophysiology of many diseases including cancer
      reforms our views on the role of biological clocks in cancer and cancer
      treatment. In the present issue the current progress in circadian clock-dependent
      mechanisms of cancer, polymorphism and mutations of clock gene in cancer, cancer
      associated clock disruptions, and novel chronotherapeutic approaches are
      discussed.

PMID- 24915533
TI  - Evans blue staining reveals vascular leakage associated with focal areas of host
      parasite interaction in brains of pigs infected with Taenia solium.
AB  - Cysticidal drug treatment of viable Taenia solium brain parenchymal cysts leads
      to an acute pericystic host inflammatory response and blood brain barrier
      breakdown (BBB), commonly resulting in seizures. Naturally infected pigs,
      untreated or treated one time with praziquantel were sacrificed at 48 hr and 120
      hr following the injection of Evans blue (EB) to assess the effect of treatment
      on larval parasites and surrounding tissue. Examination of harvested non
      encapsulated muscle cysts unexpectedly revealed one or more small, focal round
      region(s) of Evans blue dye infiltration (REBI) on the surface of otherwise non
      dye-stained muscle cysts. Histopathological analysis of REBI revealed focal areas
      of eosinophil-rich inflammatory infiltrates that migrated from the capsule into
      the tegument and internal structures of the parasite. In addition some
      encapsulated brain cysts, in which the presence of REBI could not be directly
      assessed, showed histopathology identical to that of the REBI. Muscle cysts with
      REBI were more frequent in pigs that had received praziquantel (6.6% of 3736
      cysts; n = 6 pigs) than in those that were untreated (0.2% of 3172 cysts; n = 2
      pigs). Similar results were found in the brain, where 20.7% of 29 cysts showed
      histopathology identical to muscle REBI cysts in praziquantel-treated pigs
      compared to the 4.3% of 47 cysts in untreated pigs. Closer examination of REBI
      infiltrates showed that EB was taken up only by eosinophils, a major component of
      the cellular infiltrates, which likely explains persistence of EB in the REBI.
      REBI likely represent early damaging host responses to T. solium cysts and
      highlight the focal nature of this initial host response and the importance of
      eosinophils at sites of host-parasite interaction. These findings suggest new
      avenues for immunomodulation to reduce inflammatory side effects of anthelmintic
      therapy.

PMID- 24915535
TI  - The circadian timing system in clinical oncology.
AB  - The circadian timing system (CTS) controls several critical molecular pathways
      for cancer processes and treatment effects over the 24 hours, including drug
      metabolism, cell cycle, apoptosis, and DNA damage repair mechanisms. This results
      in the circadian time dependency of whole-body and cellular pharmacokinetics and
      pharmacodynamics of anticancer agents. However, CTS robustness and phase varies
      among cancer patients, based on circadian monitoring of rest- activity, body
      temperature, sleep, and/or hormonal secretion rhythms. Circadian disruption has
      been further found in up to 50% of patients with metastatic cancer. Such
      disruption was associated with poor outcomes, including fatigue, anorexia, sleep
      disorders, and short progression-free and overall survival. Novel, minimally
      invasive devices have enabled continuous CTS assessment in non-hospitalized
      cancer patients. They revealed up to 12-hour differences in individual circadian
      phase. Taken together, the data support the personalization of chronotherapy.
      This treatment method aims at the adjustment of cancer treatment delivery
      according to circadian rhythms, using programmable-in-time pumps or novel release
      formulations, in order to increase both efficacy and tolerability. A fixed
      oxaliplatin, 5-fluorouracil and leucovorin chronotherapy protocol prolonged
      median overall survival in men with metastatic colorectal cancer by 3.3 months as
      compared to conventional delivery, according to a meta-analysis (P=0.009).
      Further analyses revealed the need for the prevention of circadian disruption or
      the restoration of robust circadian function in patients on chronotherapy, in
      order to further optimize treatment effects. The strengthening of external
      synchronizers could meet such a goal, through programmed exercise, meal timing,
      light exposure, improved social support, sleep scheduling, and the properly timed
      administration of drugs that target circadian clocks. Chrono-rehabilitation
      warrants clinical testing for improving quality of life and survival in cancer
      patients.

PMID- 24915537
TI  - Insights into the electrocatalytic reduction of CO2 on metallic silver surfaces.
AB  - The electrochemical reduction of CO2 could allow for a sustainable process by
      which renewable energy from wind and solar are used directly in the production of
      fuels and chemicals. In this work we investigated the potential dependent
      activity and selectivity of the electrochemical reduction of CO2 on metallic
      silver surfaces under ambient conditions. Our results deepen our understanding of
      the surface chemistry and provide insight into the factors important to designing
      better catalysts for the reaction. The high sensitivity of our experimental
      methods for identifying and quantifying products of reaction allowed for the
      observation of six reduction products including CO and hydrogen as major products
      and formate, methane, methanol, and ethanol as minor products. By quantifying the
      potential-dependent behavior of all products, we provide insights into kinetics
      and mechanisms at play, in particular involving the production of hydrocarbons
      and alcohols on catalysts with weak CO binding energy as well as the formation of
      a C-C bond required to produce ethanol. 

PMID- 24915539
TI  - Determinants of treatment plan implementation in multidisciplinary team meetings
      for patients with chronic diseases: a mixed-methods study.
AB  - OBJECTIVE: Multidisciplinary team (MDT) meetings are assumed to produce better
      decisions and are extensively used to manage chronic disease in the National
      Health Service (NHS). However, evidence for their effectiveness is mixed. Our
      objective was to investigate determinants of MDT effectiveness by examining
      factors influencing the implementation of MDT treatment plans. This is a proxy
      measure of effectiveness, because it lies on the pathway to improvements in
      health, and reflects team decision making which has taken account of clinical and
      non-clinical information. Additionally, this measure can be compared across MDTs
      for different conditions. METHODS: We undertook a prospective mixed-methods study
      of 12 MDTs in London and North Thames. Data were collected by observation of 370
      MDT meetings, interviews with 53 MDT members, and from 2654 patient medical
      records. We examined the influence of patient-related factors (disease, age, sex,
      deprivation, whether their preferences and other clinical/health behaviours were
      mentioned) and MDT features (as measured using the 'Team Climate Inventory' and
      skill mix) on the implementation of MDT treatment plans. RESULTS: The adjusted
      odds (or likelihood) of implementation was reduced by 25% for each additional
      professional group represented at the MDT meeting. Implementation was more likely
      in MDTs with clear goals and processes and a good 'Team Climate' (adjusted OR
      1.96; 95% CI 1.15 to 3.31 for a unit increase in Team Climate Inventory (TCI)
      score). Implementation varied by disease category, with the lowest adjusted odds
      of implementation in mental health teams. Implementation was also lower for
      patients living in more deprived areas (adjusted odds of implementation for
      patients in the most compared with least deprived areas was 0.60, 95% CI 0.39 to
      0.91). CONCLUSIONS: Greater multidisciplinarity is not necessarily associated
      with more effective decision making. Explicit goals and procedures are also
      crucial. Decision implementation should be routinely monitored to ensure the
      equitable provision of care.

PMID- 24915540
TI  - A multidisciplinary, multifaceted improvement initiative to eliminate mislabelled
      laboratory specimens at a large tertiary care hospital.
AB  - OBJECTIVES: To sustainably reduce the rate of mislabelled laboratory specimens
      through implementation of a series of interventions as led and coordinated by a
      multidisciplinary performance improvement team. METHODS: The quality improvement
      project was performed at Cedars-Sinai Medical Center in Los Angeles, an academic
      care tertiary care hospital. Phlebotomy services are provided by unit-based
      nursing and dedicated laboratory-based phlebotomists. Baseline mislabelled
      specimen rate was obtained for a 6-month period prior to the first improvement
      intervention. Included in the rate of mislabelled specimens were inpatient blood
      and body fluid specimens. Anatomic pathology and cytological specimens and
      outpatient specimens were excluded. Mislabelled specimens were identified
      preanalytically, analytically or postanalytically. A specimen was considered
      mislabelled under the following circumstances: (1) specimen/requisition mismatch;
      (2) incorrect patient identifiers and (3) unlabelled specimen. Specimen mislabels
      were identified and validated monthly by a multidisciplinary team composed of
      personnel from nursing, laboratory and performance improvement. Performance
      improvement initiatives were implemented over a 2-year period with control charts
      used to assess improvement over time. RESULTS: The rate of mislabelled specimens
      varied by clinical area and decreased significantly over a 24-month time period
      during the initiative from 4.39 per 10,000 specimens to 1.97 per 10,000
      specimens. All clinical areas achieved a significant decrease in the rate of
      mislabelled specimens except for the operating room and labour and delivery.
      CONCLUSIONS: A multidisciplinary unit specific approach using performance
      improvement methodologies focusing on human factors can reliably and sustainably
      reduce the rate of mislabelled laboratory specimens in a large tertiary care
      hospital.

PMID- 24915536
TI  - Hydrogen-rich saline promotes survival of retinal ganglion cells in a rat model
      of optic nerve crush.
AB  - OBJECTIVE: To investigate the effect of molecular hydrogen (H2) in a rat model
      subjected to optic nerve crush (ONC). METHODS: We tested the hypothesis that
      after optic nerve crush (ONC), retinal ganglion cell (RGC) could be protected by
      H2. Rats in different groups received saline or hydrogen-rich saline every day
      for 14 days after ONC. Retinas from animals in each group underwent measurements
      of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma
      synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick
      end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked
      potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate
      the function of optic nerve. The malondialdehyde (MDA) level in retina was
      evaluated. RESULTS: H&E, gamma synuclein staining and CTB tracing showed that the
      survival rate of RGCs in hydrogen saline-treated group was significantly higher
      than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining
      were less observed in hydrogen saline-treated group. The MDA level in retina of
      H2 group was much lower than that in placebo group. Furthermore, animals treated
      with hydrogen saline showed better function of optic nerve in assessments of FVEP
      and PLR. CONCLUSION: These results demonstrated that H2 protects RGCs and helps
      preserve the visual function after ONC and had a neuroprotective effect in a rat
      model subjected to ONC.

PMID- 24915541
TI  - Intracellular bacteria interfere with dendritic cell functions: role of the type
      I interferon pathway.
AB  - Dendritic cells (DCs) orchestrate host defenses against microorganisms. In
      infectious diseases due to intracellular bacteria, the inefficiency of the immune
      system to eradicate microorganisms has been attributed to the hijacking of DC
      functions. In this study, we selected intracellular bacterial pathogens with
      distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs).
      Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the
      causative agent of scrub typhus that survives in the cytosol of target cells,
      induced moDC maturation, as assessed by decreased endocytosis activity, the
      ability to induce lymphocyte proliferation and the membrane expression of
      phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and
      Brucella abortus, the agent of brucellosis, both of which reside in vacuolar
      compartments, only partly induced the maturation of moDCs, as demonstrated by a
      phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus
      to alter moDC activation, we performed microarray and found that C. burnetii and
      B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and
      interferon response genes. These genes were down-modulated in response to C.
      burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide
      and O. tsutsugamushi. This transcriptional alteration was associated with the
      defective interferon-beta production. This study demonstrates that intracellular
      bacteria specifically affect moDC responses and emphasizes how C. burnetii and B.
      abortus interfere with moDC activation and the antimicrobial immune response. We
      believe that comparing infection by several bacterial species may be useful for
      defining new pathways and biomarkers and for developing new treatment strategies.

PMID- 24915542
TI  - Adjustable degradation properties and biocompatibility of amorphous and
      functional poly(ester-acrylate)-based materials.
AB  - Tuning the properties of materials toward a special application is crucial in the
      area of tissue engineering. The design of materials with predetermined
      degradation rates and controlled release of degradation products is therefore
      vital. Providing a material with various functional groups is one of the best
      ways to address this issue because alterations and modifications of the polymer
      backbone can be performed easily. Two different 2-methylene-1,3
      dioxepane/glycidyl methacrylate-based (MDO/GMA) copolymers were synthesized with
      different feed ratios and immersed into a phosphate buffer solution at pH 7.4 and
      in deionized water at 37  degrees C for up to 133 days. After different time
      intervals, the molecular weight changes, mass loss, pH, and degradation products
      were determined. By increasing the amount of GMA functional groups in the
      material, the degradation rate and the amount of acidic degradation products
      released from the material were decreased. As a result, the composition of the
      copolymers greatly affected the degradation rate. A rapid release of acidic
      degradation products during the degradation process could be an important issue
      for biomedical applications because it might affect the biocompatibility of the
      material. The cytotoxicity of the materials was evaluated using a MTT assay.
      These tests indicated that none of the materials demonstrated any obvious
      cytotoxicity, and the materials could therefore be considered biocompatible. 

PMID- 24915545
TI  - New directions in diagnostic evaluation of insect allergy.
AB  - PURPOSE OF REVIEW: Diagnosis of insect sting allergy and prediction of risk of
      sting anaphylaxis are often difficult because tests for venom-specific IgE
      antibodies have a limited positive predictive value and do not reliably predict
      the severity of sting reactions. RECENT FINDINGS: Component-resolved diagnosis
      using recombinant venom allergens has shown promise in improving the specificity
      of diagnostic testing for insect sting allergy. Basophil activation tests have
      been explored as more sensitive assays for identification of patients with insect
      allergy and for prediction of clinical outcomes. Measurement of mast cell
      mediators reflects the underlying risk for more severe reactions and limited
      clinical response to treatment. SUMMARY: Measurement of IgE to recombinant venom
      allergens can distinguish cross-sensitization from dual sensitization to honeybee
      and vespid venoms, thus helping to limit venom immunotherapy to a single venom
      instead of multiple venoms in many patients. Basophil activation tests can detect
      venom allergy in patients who show no detectable venom-specific IgE in standard
      diagnostic tests and can predict increased risk of systemic reactions to venom
      immunotherapy, and to stings during and after stopping venom immunotherapy. The
      risk of severe or fatal anaphylaxis to stings can also be predicted by
      measurement of baseline serum tryptase or other mast cell mediators.

PMID- 24915544
TI  - Peri-transplant psychosocial factors and neutrophil recovery following
      hematopoietic stem cell transplantation.
AB  - OBJECTIVE: Multiple psychosocial factors appear to affect cancer progression in
      various populations; however, research investigating the relationship between
      psychosocial factors and outcomes following hematopoietic stem cell
      transplantation (HCT) is scarce. Subject to adverse immunological and
      psychological conditions, HCT patients may be especially vulnerable to
      psychosomatic health sequelae; therefore, we studied whether optimism and anxiety
      influence the pertinent clinical outcome of days to neutrophil engraftment (DTE).
      METHOD: 54 adults undergoing either autologous or allogeneic HCT completed self
      report questionnaires measuring optimism and anxiety. We assessed the association
      between these psychosocial variables and DTE. RESULTS: Greater optimism and less
      anxiety were associated with the favorable outcome of fewer DTE in autologous HCT
      recipients, though this relationship was no longer significant when reducing the
      sample size to only subjects who filled out their baseline survey by the time of
      engraftment. CONCLUSION: Our findings are suggestive that optimism and anxiety
      may be associated with time to neutrophil recovery in autologous, but not
      allogeneic, adult HCT recipients. Further investigation in larger, more
      homogeneous subjects with consistent baseline sampling is warranted.

PMID- 24915546
TI  - Mechanisms of drug-induced liver injury.
AB  - PURPOSE OF REVIEW: Idiosyncratic drug-induced liver injury (iDILI) is a
      relatively rare condition, but can have serious consequences for the individual
      patient, public health, regulatory agencies and the pharmaceutical industry.
      Despite increased awareness of iDILI, its underlying mechanism is still not fully
      understood. This review summarizes the current understanding of the molecular
      mechanism behind iDILI. RECENT FINDINGS: Genetic variations in drug metabolizing
      genes are in line with proposed mechanisms based on acetaminophen hepatotoxicity,
      whereby reactive metabolites covalently bind to cellular proteins and disturb the
      redox balance. In addition, immune-mediated effects have been reported for
      flucloxacillin hepatotoxicity, demonstrating both haptenization and direct
      binding between the drug and immune receptors. SUMMARY: Idiosyncratic DILI
      development is believed to be orchestrated by multiple events, such as reactive
      metabolite formations, oxidative stress and signalling pathway inductions, with
      the mitochondria taking centre stage. Evidence also points towards the immune
      system (innate and adaptive responses) as important components in iDILI.
      Interindividual differences in one or more of these events, due to genetic
      variations and environmental factors, are likely to contribute to the
      idiosyncratic nature of this condition and subsequently distinguish between
      patient susceptibility and tolerance.

PMID- 24915543
TI  - Effects of fish oil supplementation on prefrontal metabolite concentrations in
      adolescents with major depressive disorder: a preliminary 1H MRS study.
AB  - OBJECTIVE: To use proton magnetic resonance spectroscopy ((1)H MRS) to
      investigate the effects of fish oil (FO) supplementation on cortical metabolite
      concentrations in adolescents with major depressive disorder (MDD). METHODS:
      Metabolite concentrations were determined by (1)H MRS in the anterior cingulate
      cortex and bilateral dorsolateral prefrontal cortex (DLPFC) of adolescents with
      MDD before and following 10-week open-label supplementation with low (2.4 g/day,
      n = 7) or high (16.2 g/day, n = 7) dose FO. Depressive symptom severity scores
      and erythrocyte fatty acid levels were also determined. RESULTS: Baseline
      erythrocyte eicosapentaenoic acid (EPA) composition was positively correlated,
      and arachidonic acid (AA) and the AA/EPA ratio were inversely correlated, with
      choline (Cho) concentrations in the right DLPFC. Docosahexaenoic acid (DHA)
      composition was inversely correlated with myo-inositol (mI) concentrations in the
      left DLPFC. Erythrocyte EPA and DHA composition increased, and AA decreased,
      significantly following low-dose and high-dose FO supplementation. In the intent
      to-treat sample, depressive symptom severity scores decreased significantly in
      the high-dose group (-40%, P < 0.0001) and there was a trend in the low-dose
      group (-20%, P = 0.06). There were no significant baseline-endpoint changes in
      metabolite levels in each voxel. In the low-dose group there were changes with
      large effect sizes, including a decrease in mI in the left DLPFC (-12%, P = 0.18,
      d = 0.8) and increases in glutamate + glutamine (Glx) (+12%, P = 0.19, d = 0.8)
      and Cho (+15%, P = 0.08, d = 1.2) in the right DLPFC. In the high-dose group,
      there was a trend for increases in Cho in the right DLPFC (+10%, P = 0.09, d =
      1.2). DISCUSSION: These preliminary data suggest that increasing the LCn-3 fatty
      acid status of adolescent MDD patients is associated with subtle changes in Glx,
      mI, and Cho concentrations in the DLPFC that warrant further evaluation in a
      larger controlled trial.

PMID- 24915547
TI  - Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: from
      phenotyping to genotyping.
AB  - PURPOSE OF REVIEW: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most
      frequent drugs involved in hypersensitivity drugs reactions. Both immunological
      and nonimmunological mechanisms can be involved. We describe the different
      phenotypes as well as analyze the genetic basis for NSAIDs hypersensitivity.
      RECENT FINDINGS: Five major clinical entities are currently accepted in the
      classification of hypersensitivity reactions to NSAIDs. Three are mediated by
      nonspecific immunological mechanisms: NSAIDs-exacerbated respiratory disease,
      NSAIDs-exacerbated cutaneous disease and NSAIDs-induced urticaria/angioedema. Two
      are mediated by specific immunological mechanisms: single-NSAID-induced
      urticaria/angioedema or anaphylaxis and single-NSAID-induced delayed
      hypersensitivity reactions. The classification becomes more complex if we
      consider that in an important number of cases skin and airway involvement can
      occur, as well as the participation of other organs. SUMMARY: Hypersensitivity
      reactions to NSAIDs are more complex than for other drugs like betalactams in
      terms of the number and types of reactions elicited, and mechanisms involved. As
      NSAIDs are the most frequent cause of drug hypersensitivity, it is feasible to
      gather a sufficient number of cases for undertaking pharmacogenetic studies.

PMID- 24915548
TI  - Anaphylaxis and cardiovascular diseases: a dangerous liaison.
AB  - PURPOSE OF REVIEW: Anaphylaxis is a life-threatening event in which the
      cardiovascular system is responsible for the majority of clinical symptoms and
      for potentially fatal outcome. This review summarizes the most recent clinical
      and experimental data on cardiovascular involvement during anaphylaxis. RECENT
      FINDINGS: Great efforts have been made in the last few years to understand the
      pathophysiology of anaphylactic reaction and to provide better identification of
      risk factors for the development of this reaction. Coronary blood flow can be
      impaired during anaphylaxis, which may significantly contribute to an
      unfavourable outcome. Also, preexisting coronary artery disease is a negative
      prognostic factor for anaphylaxis. In addition, acute ischemic events, including
      angina and myocardial infarction, are currently considered as part of the
      clinical picture of anaphylaxis. Moreover, cardiac emergency can be the
      presenting clinical picture of mast cell-related disorders. SUMMARY: Both
      cardiovascular and allergic diseases are frequent among populations. A better
      understanding of the mechanisms leading to cardiac mast cell activation and the
      effects of mast cell mediators on cardiovascular system can help improve the
      prevention and treatment of anaphylaxis.

PMID- 24915549
TI  - Functionalization of boron-doped nanocrystalline diamond with N3 dye molecules.
AB  - N3 dye molecules [cis-bis(isothiocyanato)bis(2,2'-bipyridyl-4,4'
      dicarboxylato)ruthenium(II)] are covalently attached to boron-doped
      nanocrystalline diamond (B:NCD) thin films through a combination of coupling
      chemistries, i.e., diazonium, Suzuki, and EDC-NHS. X-ray and ultraviolet
      photoelectron spectroscopy and near-edge X-ray absorption fine structure
      spectroscopy are used to verify the covalent bonding of the dye on the B:NCD
      surface (compared to a hydrogen-terminated reference). The spectroscopic results
      confirm the presence of a dense N3 chromophore layer, and the positions of the
      frontier orbitals of the dye relative to the band edge of the B:NCD thin film are
      inferred as well. Proof-of-concept photoelectrochemical measurements show a
      strong increase in the photocurrent compared to non-dye-functionalized B:NCD
      films. This study opens up the possibility of applying N3-sensitized B:NCD thin
      films as hole conductors in dye-sensitized solar cells.

PMID- 24915550
TI  - Formulation of extended release cefpodoxime proxetil chitosan-alginate beads
      using quality by design approach.
AB  - The purpose of this work was to develop and characterize chitosan-alginate beads
      for the extended delivery of cefpodoxime proxetil (CFP), to understand the impact
      of formulation and process parameters on the critical quality attributes (CQAs)
      using a quality-by-design approach. For this, a study was performed with various
      formulation and process parameters to determine their impact on CQAs of beads,
      which were determined to be time for 80% of the drug released (T80%), particle
      size, and encapsulation efficiency. The beads of CFP were optimized using a three
      factor, three-level Box-Behnken design. A formulation comprising of 4.38% (w/v)
      alginate, 1.39% (w/v) chitosan and 6.82% (w/v) calcium chloride was found to
      fulfill requisites of an optimum formulation. In vitro release studies showed
      that the drug is released from the optimized formulation over a period of 24h in
      a sustained release manner, primarily by non-Fickian diffusion. The optimized
      formulation was characterized by DSC, FTIR, XRD and SEM analysis. Antimicrobial
      studies revealed that the release of the drug over 24h periods was above the
      minimum concentration required for inhibition of microbial growth. This research
      highlights the level of understanding that can be accomplished through a well
      designed study based on the approach of QbD. 

PMID- 24915551
TI  - Safety of Metformin in Patients with Chronic Obstructive Pulmonary Disease and
      Type 2 Diabetes Mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is commonly associated with chronic obstructive
      pulmonary disease (COPD). Metformin is a valuable treatment for T2DM, and may
      offer additional benefits in COPD. However, due to its rare association with
      lactic acidosis, its safety in COPD is uncertain. We retrospectively identified
      patients with T2DM who had been admitted to hospital for COPD exacerbations. We
      compared those who were taking metformin with those who were not, with respect to
      their lactate concentration (primary endpoint) and survival (secondary endpoint).
      The study cohort (n = 130) had a mean (+/-standard deviation) age of 73.0 +/- 9.8
      years and 47 (36%) were female. Arterial blood gases were recorded in 120 cases:
      88 (73%) were hypoxemic, 45 (38%) were in respiratory failure and 33 (28%) had
      respiratory acidosis. The 51 patients (39%) in the metformin group had a median
      (interquartile range) lactate concentration of 1.45 mmol/L (1.10-2.05) versus
      1.10 mmol/L (0.80-1.50) in the non-metformin group (p = 0.012). Median survival
      was 5.2 years (95% CI 4.5-5.8) versus 1.9 years (1.1-2.6), respectively (hazard
      ratio 0.57; 95% CI 0.35-0.94). This remained significant in a multivariate model
      adjusted for measurable confounders. In conclusion, among patients with COPD at
      high risk for lactate accumulation, metformin therapy was associated with a minor
      elevation of lactate concentration of doubtful clinical significance. Metformin
      was associated with a survival benefit, but this must be interpreted cautiously
      due to possible effects from unmeasured confounders. Viewed collectively, the
      results suggest that COPD should not present a barrier to the investigational or
      clinical use of metformin.

PMID- 24915552
TI  - Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial
      densities in healthy adults.
AB  - Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary
      precursor to pneumococcal diseases that result in morbidity and mortality
      worldwide. The nasopharynx is also host to other bacterial species, including the
      common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella
      catarrhalis. To better understand how these bacteria change in relation to
      pneumococcal colonization, we used species-specific quantitative PCR to examine
      bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after
      controlled inoculation of healthy human adults with S. pneumoniae serotype 6B.
      Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The
      baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis
      were not statistically associated with likelihood of successful pneumococcal
      colonization at this study's sample size, although a lower rate of pneumococcal
      colonization in the presence of S. aureus (7/14) was seen compared to that in the
      presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the
      number also carrying either H. influenzae or S. aureus fell during the study and
      at 14 days post-inoculation, the proportion carrying S. aureus was significantly
      lower among those who were colonized with S. pneumoniae (p = 0.008) compared to
      non-colonized subjects. These data on bacterial associations are the first to be
      reported surrounding experimental human pneumococcal colonization and show that
      co-colonizing effects are likely subtle rather than absolute.

PMID- 24915553
TI  - Glucocerebrosidase deficits in sporadic Parkinson disease.
AB  - Parkinson disease (PD) is a progressive neurodegenerative movement disorder
      characterized pathologically by abnormal SNCA/alpha-synuclein protein inclusions
      in neurons. Impaired lysosomal autophagic degradation of cellular proteins is
      implicated in PD pathogenesis and progression. Heterozygous GBA mutations,
      encoding lysosomal GBA/glucocerebrosidase (glucosidase, beta, acid), are the
      greatest genetic risk factor for PD, and reduced GBA and SNCA accumulation are
      related in PD models. Here we review our recent human brain tissue study
      demonstrating that GBA deficits in sporadic PD are related to the early
      accumulation of SNCA, and dysregulation of chaperone-mediated autophagy (CMA)
      pathways and lipid metabolism. 

PMID- 24915554
TI  - Fetal diagnosis and interventions.

PMID- 24915555
TI  - Interpregnancy changes in maternal weight and body mass index.
AB  - OBJECTIVE: This longitudinal study compared changes in maternal weight and body
      mass index (BMI) in early pregnancy in the time interval between when a woman
      first attended for antenatal care with her first child and when she next attended
      for antenatal care. STUDY DESIGN: We studied women with a singleton pregnancy who
      delivered their first baby weighing >= 500 g in 2009 and who attended again for
      antenatal care with an ongoing pregnancy before January 1, 2012. Maternal weight
      and height were measured before 18 weeks' gestation in both pregnancies and BMI
      was calculated. RESULTS: Of the 3,284 primigravidas, the mean weight at the first
      visit in 2009 was 66.4 kg (standard deviation [SD] 12.7). The mean BMI was 24.5
      kg/m(2) (SD 4.6), and 11.3% (n = 370) were obese. Of the 3,284 women, 1,220
      (37.1%) re-attended for antenatal care before 2012 after sonographic confirmation
      of an ongoing pregnancy. Of the 1,220 women who re-attended, 788 (64.6%) had
      gained weight (mean 4.6 kg [SD 3.9]), 402 (33%) had lost weight (mean 3 kg [SD
      2.9]), and 30 (2.4%) had maintained their weight. CONCLUSION: The birth of a
      first baby was associated with an increase in maternal weight in two-thirds of
      women when they next attended for antenatal care.

PMID- 24915556
TI  - Severe bronchopulmonary dysplasia is associated with higher fluid intake in very
      low-birth-weight infants: a retrospective study.
AB  - OBJECTIVE: This study aims to investigate the association between fluid intake in
      the first 4 days of life and the subsequent severity of bronchopulmonary
      dysplasia (BPD) in very low-birth-weight infants (VLBWI). STUDY DESIGN: A
      retrospective chart review of 75 infants with a gestational age of less than 32
      weeks and a birth weight of < 1,500 g was performed. Demographic, clinical data,
      associated maternal risk factors, and amount of fluid received in the first 4
      days of life were analyzed. RESULTS: Severe BPD was associated with a lower
      gestational age (27.04 +/- 2.073 wks vs. 28.70 +/- 1.706 wks, p=0.001), lower
      birth weight (981.44 +/- 244.54 vs. 1,199.63 +/- 165.39 g, p < 0.001), use of
      surfactant (91.7 vs. 63%, p=0.002), patent ductus arteriousus (PDA) (70.8 vs.
      37%, p=0.004), pulmonary hemorrhage (14.6 vs. 0%, p=0.045), and more fluids
      received from the 2nd to 4th days of life (346.44 +/- 42.38 mL/kg vs. 323.91 +/-
      27.62 mL/kg, p=0.007). A cut off point of 345 mL/kg of fluids from the 2nd to 4th
      days of life was selected using receiver operating characteristic curve analysis,
      and remained a significant risk factor even after multiple logistic regression
      analysis. CONCLUSION: Our findings demonstrate that VLBWI who received higher
      fluid intake from the 2nd to 4th days of life are at an increased risk of
      developing severe BPD.

PMID- 24915557
TI  - Optimal timing of delivery in small for gestational age fetuses near term: a
      national cohort study.
AB  - OBJECTIVE: Our aim was to study the competing risks of antepartum versus
      intrapartum/neonatal death in small for gestational age (SGA) and non-SGA
      fetuses. STUDY DESIGN: We performed a national cohort study using all singletons
      delivered between 36 and 42(6/7) weeks without hypertension, preeclampsia,
      diabetes, congenital anomalies, or noncephalic presentation from the Netherlands
      Perinatal Registry (1999-2007). The resultant cohort was divided in three groups
      based on birth weight by gestational age (SGA < P5 group, 61,021 deliveries; SGA
      P5-10 group, 58,902 deliveries; non-SGA group 1,168,523 deliveries). We compared
      the mortality risk of delivery with expectant management. RESULTS: Delivery was
      associated with more mortality than expectant management for 1 week from 39 weeks
      onward in the non-SGA group (relative risk [RR], 1.26; 95% confidence interval
      [CI], 1.05-1.50). For the SGA < P5, expectant management for 1 more week was
      associated with more mortality from 38 weeks onward although this only reached
      statistical significance from 40 weeks onward (RR, 2.46; 95% CI, 1.80-3.36).
      CONCLUSION: At 36 and 37 weeks, delivery is associated with a higher risk of
      mortality in SGA < P5 fetuses than expectant management. Delivery of SGA < P5
      fetuses at 38 and 39 weeks is associated with the best perinatal outcome whereas
      for non-SGA fetuses this is at 39 to 40 weeks.

PMID- 24915558
TI  - Using WINROP as an adjuvant screening tool for retinopathy of prematurity in
      southern Taiwan.
AB  - OBJECTIVE: To study the efficacy of the WINROP (https://winrop.com) algorithm in
      Taiwan, a middle income, moderately developed country in Asia. STUDY DESIGN: We
      enrolled all preterm infants born with a gestational age less than 32(+0) weeks
      from September 2008 to August 2010. The results of serial retinopathy of
      prematurity examinations according to the screening guidelines in our hospital
      were recorded. Weekly body weight was also recorded for the WINROP algorithm. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value were calculated. RESULTS: Overall, 148 infants were included. Seventeen
      infants (11.5%) received treatment for retinopathy of prematurity. But, six
      infants (35.3%) were missed when severe retinopathy of prematurity was predicted
      with WINROP algorithm. The sensitivity is only 64.7%. However, when focusing on
      the preterm infants with a birth weight < 1,000 g or gestational age < 28 weeks,
      it could predict the need for treatment up to 13 weeks in advance. CONCLUSION:
      The WINROP algorithm is a very effective noninvasive screening tool for
      retinopathy of prematurity, especially in preterm infants with a birth weight  <
      1,000 g or a gestational age < 28 weeks. However, the overall sensitivity in this
      report from Taiwan was not as high as that reported in highly developed
      countries.

PMID- 24915559
TI  - Maternal glucose response to betamethasone administration.
AB  - OBJECTIVE: This study aims to describe the pattern of maternal glucose response
      to betamethasone administration using a continuous glucose monitoring system.
      STUDY DESIGN: A prospective observational trial was conducted among women
      receiving clinically indicated betamethasone between 24 and 34 weeks gestation.
      At the time of initial betamethasone administration, a continuous glucose
      monitoring device was inserted which measured interstitial fluid glucose levels
      every 5 minutes. Glucose levels were monitored for 7 days, until delivery, or
      until hospital discharge, whichever came first. We recorded the percentage of
      time women spent above three glucose thresholds: 110, 144, and 180 mg/dL,
      respectively. RESULTS: A total of 17 women were enrolled at the time of
      betamethasone administration and data were available for 15 patients. There were
      11 nondiabetic and 4 diabetic women. Both diabetic and nondiabetic women had the
      highest recorded blood glucose readings between 24 and 48 hours after the first
      injection of betamethasone. In that period, nondiabetic women spent 73, 40, and
      17% of the time with blood glucose levels above the 110, 144, and 180 mg/dL
      thresholds, respectively. CONCLUSION: Nondiabetic women receiving betamethasone
      manifest significant hyperglycemia after betamethasone administration. If
      delivery is imminent, maternal glucose response to betamethasone may need to be
      monitored to prevent possible neonatal hypoglycemia.

PMID- 24915560
TI  - Use of noninvasive high-frequency ventilation in the neonatal intensive care
      unit: a retrospective review.
AB  - OBJECTIVE: The aim of the article is to review the effectiveness of neonatal
      noninvasive high-frequency ventilation (NIHFV) in preventing endotracheal
      mechanical ventilation. STUDY DESIGN: Retrospective case series including all 79
      instances of NIHFV use at four participating centers between July 2010 and
      September 2012. RESULTS: In 73% of cases, NIHFV was used as rescue after another
      noninvasive mode, and prophylactically (postextubation) in the remainder. In 58%
      of cases, infants transitioned to another noninvasive mode, without requiring
      intubation. There were significant reductions in the mean (SD) number of apneas,
      bradycardias, or desaturations (over 6 hours) (3.2 [0.4] vs. 1.2 [0.3]; p <
      0.001), FiO2 (48 [3] vs. 40 [2]%; p < 0.001) and CO2 levels (74 [6] vs. 62 [4] mm
      Hg; p = 0.025] with NIHFV. No NIHFV-related complications were noted.
      CONCLUSIONS: NIHFV is a promising NIV mode that may help prevent or delay
      intubation and deserves further clinical research.

PMID- 24915561
TI  - Levels of ischemia-modified albumin in transient tachypnea of the newborn.
AB  - AIM: The aim of the article is to evaluate ischemia-modified albumin (IMA) levels
      in infants with transient tachypnea of the newborn (TTN) and to find out its
      relation to the disease severity. Patients and METHODS: Infants with > 37 weeks
      of gestation, without any respiratory and cardiac symptoms and without any
      maternal health problems, and diagnosed as TTN were allocated as the study group.
      Patients with obvious retractions, grunting, hypercarbia (Pco 2 > 60 mm Hg) or
      hypoxia (oxygen saturation < 88% with Fio 2 of 0.60) were managed with nasal
      continuous positive airway pressure (CPAP). During the postnatal 0 to 24 hours,
      blood samples were collected in 2 mL for IMA. RESULTS: A total of 47 patients
      were diagnosed TTN, and allocated as the study group. Of the 47 patients, 43
      patients without respiratory symptoms were enrolled as the control group. IMA
      levels in TTN were found to be significantly higher (p < 0.05). In addition, IMA
      levels were significantly increased in the nasal CPAP group versus supplemental
      oxygen therapy groups (p < 0.05). IMA levels were determined to be significantly
      higher in the > 3 days of oxygen therapy group (p < 0.05). IMA levels with a
      cutoff point of 0.87 ABSU, sensitivity of 81.1% and specificity of 69.8%
      predicted TTN (area under the curve [AUC] = 0.85; p < 0.05). IMA levels with >
      0.98 ABSU, 78% sensitivity, and 86% specificity indicated the prediction of CPAP
      requirement (AUC = 0.86; p < 0.05). CONCLUSION: IMA levels were significantly
      higher in infants with diagnosed TTN. Therefore, IMA may be used as a new marker
      for predicting TTN and disease severity.

PMID- 24915562
TI  - Effects of Saccharomyces boulardii on neonatal hyperbilirubinemia: a randomized
      controlled trial.
AB  - OBJECTIVE: Since probiotics modulate intestinal functions and enterohepatic
      circulation; they might have an effect on neonatal hyperbilirubinemia treatment.
      The objective of this study was to investigate the efficacy of Saccharomyces
      boulardii supplementation on hyperbilirubinemia. STUDY DESIGN: A prospective,
      double-blind, placebo controlled trial was performed on 35 to 42 gestational
      weeks' neonates. They were randomized either to receive feeding supplementation
      with S. boulardii 125 mg every 12 hours or placebo during phototherapy. Serum
      bilirubin levels were measured at 0, 24th, 48th, 72nd, and 96th hour of
      phototherapy. RESULTS: A total of 119 infants (61 in the control group and 58 in
      the study group) were enrolled. The duration of phototherapy (2 [1-3] vs. 2 [1
      3], p: 0.22) was not different between groups. The levels of bilirubin during
      phototherapy ([24th hour; 14.1 {12.8-15.7} vs. 13.5 {12.4-14.9}, p: 0.085]; [48th
      hour; 14.1 {12-15.3} vs. 13.4 {12.4-14.5}, p: 0.41]; [72nd hour; 13.9 {12.2-15.6}
      vs. 13.5 {12.5-14.5}, p: 0.41]; [96th hour; 14.7 {11.4-15.5} vs. 13.4 {10.7
      14.1}, p: 0.24]) or the duration of rebound phototherapy (1 [1-1] vs. 1.5 [1-2],
      p: 0.40) were lower in the study group than in the controls, but none of the
      values were statistically significant. CONCLUSION: S. boulardii did not influence
      the clinical course of hyperbilirubinemia significantly.

PMID- 24915563
TI  - Labor outcomes of obese patients undergoing induction of labor with misoprostol
      compared to dinoprostone.
AB  - OBJECTIVE: The aim of the article is to evaluate and compare labor outcomes in
      obese patients undergoing induction of labor (IOL) with misoprostol and
      dinoprostone. STUDY DESIGN: This was a retrospective review of patients who
      delivered from February 1, 2008, to July 1, 2013 at our institution. All obese
      women who underwent IOL were identified. The rates of successful cervical
      ripening and cesarean delivery (CD) for patients who underwent IOL with
      misoprostol and dinoprostone were calculated and compared. RESULTS: A total of
      564 women met inclusion criteria; 297 (52.7%) were induced with misoprostol, and
      267 (47.3%) were induced with dinoprostone. The misoprostol group had a higher
      successful cervical ripening rate (78.1 vs. 66.7%; odds ratio [OR], 1.79; 95%
      confidence interval [CI], 1.23-2.6; p = 0.002) and a lower CD rate (39.1 vs.
      51.3%; OR, 0.61; 95% CI, 0.44-0.85; p = 0.003) than the dinoprostone group. This
      significance persisted in a multivariate model adjusting for parity, gestational
      age, birth weight, and indication for IOL. The rates of tachysystole, terbutaline
      use, postpartum hemorrhage, and infectious morbidity were comparable in both
      groups, as were Apgar scores, rates of neonatal intensive care unit admission,
      and meconium passage. CONCLUSION: In obese women undergoing IOL, misoprostol
      leads to a higher successful cervical ripening rate and a lower CD rate than
      dinoprostone, with a similar rate of peripartum complications and neonatal
      outcomes.

PMID- 24915564
TI  - Twin-to-twin transfusion syndrome--30 years at the front.
AB  - Thirty years ago, twin-to-twin transfusion syndrome (TTTS) was one of the most
      challenging problems of modern obstetrics. The associated mortality and morbidity
      was staggering, and a sense of hopelessness prevailed among clinicians and
      pediatric pathologists. Technical advances in ultrasound, endoscopy, video
      recording, and medical lasers formed the basis for diagnosis and in utero therapy
      of placental disorders. We review some historical events which gave rise to a new
      treatment modality for TTTS, fetoscopic laser occlusion of chorioangiopagous
      vessels, now the most common operation performed worldwide in behalf of fetuses
      in peril. 

PMID- 24915565
TI  - Fetal echocardiography in twin-twin transfusion syndrome.
AB  - Twin-twin transfusion syndrome is a complex disease process affecting
      monochorionic twin pregnancies that has implications for the cardiovascular
      system in both recipient and donor cotwins. Systolic, diastolic, and structural
      cardiac changes can occur; these have been the subject of intense study over the
      past two decades, and the use of echocardiography in evaluation of these
      pregnancies has become common in centers offering treatment of the condition. The
      role of echocardiography, the clinical cardiovascular and hemodynamic findings
      characteristic of the syndrome, and proposed pathophysiologic mechanisms and
      consequences are discussed in this review. Emerging technologies will be
      presented along with proposed areas for future research. 

PMID- 24915566
TI  - Evaluation physical characteristics and comparison antimicrobial and anti
      inflammation potentials of dental root canal sealers containing hinokitiol in
      vitro.
AB  - Hinokitiol displays potent antimicrobial activity. It has been used in toothpaste
      and oral-care gel to improve the oral lichen planus and reduce halitosis. The aim
      of this study was to evaluate the antimicrobial activity of 3 different dental
      root canal sealers with hinokitiol (sealers+H) and their physical and biological
      effects. AH Plus (epoxy amine resin-based, AH), Apexit Plus (calcium-hydroxide
      based, AP), and Canals (zinc-oxide-eugenol-based, CA), were used in this study.
      The original AH and CA exhibited strong anti-methicillin-resistant Staphylococcus
      aureus (anti-MRSA) activity, but AP did not. The setting time, working time,
      flowability, film thickness, and solubility of each sealer+0.2%H complied with
      ISO 6876:2001. CA+0.2%H exhibited high cytotoxicity, but the others sealers+0.2%H
      did not. Because hinokitiol combined with Zn2+ in CA creates a synergistic
      effect. The physical tests of AP+0.5%-1%H complied with ISO 6876:2001, improved
      antimicrobial activity, inhibited inflammation genes cyclooxygenase-2 (COX-2) and
      hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA in MG-63 cells and human
      gingival fibroblasts (HGF), and down-regulated lysyl oxidase (LOX) mRNA of HGF.
      In summary, AH and CA demonstrated strong antimicrobial activity, but AP did not.
      Application of hinokitiol increases AH anti-MRSA activity should less than 0.2%
      for keep well flowability. AP+0.5%-1% hinokitiol exhibited strong physical,
      antibacterial, and anti-inflammation potentials, and inhibited S. aureus abscess
      formation. Applying an appreciable proportion of hinokitiol to epoxy-amine-resin
      based and calcium-hydroxide-based root canal sealers is warranted, but the
      enhanced cytotoxicity and synergistic effect must be considered. 

PMID- 24915567
TI  - Intracellular cleavage of amyloid beta by a viral protease NIa prevents amyloid
      beta-mediated cytotoxicity.
AB  - Nuclear inclusion a (NIa) of turnip mosaic virus is a cytosolic protease that
      cleaves amyloid beta (Abeta) when heterologously overexpressed. Lentivirus
      mediated expression of NIa in the brains of APP(sw)/PS1 mice significantly
      reduces cerebral Abeta levels and plaque depositions, and improves behavioral
      deficits. Here, the effects of NIa and neprilysin (NEP), a well-known Abeta
      cleaving protease, on oligomeric Abeta-induced cell death were evaluated. NIa
      cleaved monomeric and oligomeric Abeta at a similar rate, whereas NEP only
      cleaved monomeric Abeta. Oligomeric Abeta-induced cytotoxicity and mitochondrial
      dysfunction were significantly ameliorated by NIa, but not by NEP. Endocytosed
      fluorescently-labeled Abeta localized to mitochondria, and this was significantly
      reduced by NIa, but not by NEP. These data suggest that NIa may exerts its
      protective roles by degrading Abeta and thus preventing mitochondrial deposition
      of Abeta. 

PMID- 24915568
TI  - Correlation between serum tryptase, mast cells positive to tryptase and
      microvascular density in colo-rectal cancer patients: possible biological
      clinical significance.
AB  - BACKGROUND: Tryptase is a serin protease stored and released from mast cells
      (MCs) that plays a role in tumour angiogenesis. In this study we aimed to
      evaluate serum tryptase levels in colo-rectal cancer (CRC) patients before
      (STLBS) and after (STLAS) radical surgical resection. We also evaluated mast cell
      density positive to tryptase (MCDPT) and microvascular density (MVD) in primary
      tumour tissue. METHODS: A series of 61 patients with stage B and C CRC (according
      to the Astler and Coller staging system) were selected. Serum blood samples were
      collected from patients one day before and one day after surgery. Tryptase levels
      were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia,
      Uppsala, Sweden). Tumour sections were immunostained with a primary anti-tryptase
      antibody (clone AA1; Dako, Glostrup, Denmark) and an anti CD-34 antibody (QB-END
      10; Bio-Optica Milan, Italy) by means of immunohistochemistry and then evaluated
      by image analysis methods. RESULTS: The mean +/- s.d. STLBS and STLAS was 5.63+/
      2.61 ug/L, and 3.39+/-1.47 ug/L respectively and a significant difference between
      mean levels was found: p = 0.000 by t-test. The mean +/- s.d. of MCDPT and MVD
      was 8.13+/-3.28 and 29.16+/-7.39 respectively. A strong correlation between STLBS
      and MVD (r = 0.83, p = 0.000); STLBS and MCDPT (r = 0.60, p = 0.003); and MCDPT
      and MVD (r = 0.73; p = 0.001) was found. CONCLUSION: Results demonstrated higher
      STLBS in CRC patients, indicating an involvement of MC tryptase in CRC
      angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase
      from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as
      a novel bio-marker predictive of response to radical surgery. In this context
      tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated
      in adjuvant clinical trials as a new anti-angiogenic approach.

PMID- 24915569
TI  - Expression of PD-L1 on canine tumor cells and enhancement of IFN-gamma production
      from tumor-infiltrating cells by PD-L1 blockade.
AB  - Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death
      ligand 1 (PD-L1), its ligand, together induce the "exhausted" status in antigen
      specific lymphocytes and are thus involved in the immune evasion of tumor cells.
      In this study, canine PD-1 and PD-L1 were molecularly characterized, and their
      potential as therapeutic targets for canine tumors was discussed. The canine PD-1
      and PD-L1 genes were conserved among canine breeds. Based on the sequence
      information obtained, the recombinant canine PD-1 and PD-L1 proteins were
      constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal
      antibody effectively blocked the binding of recombinant PD-1 with PD-L1
      expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal
      cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some
      did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-gamma
      production from tumor-infiltrating cells. These results showed that the canine PD
      1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and
      that its blockade with antibody could be a new therapeutic strategy for canine
      tumors. Further investigations are needed to confirm the ability of anti-PD-L1
      antibody to reactivate canine antitumor immunity in vivo, and its therapeutic
      potential has to be further discussed. 

PMID- 24915571
TI  - Liver proliferation: the GUCD1/NEDD4-1 connection.

PMID- 24915570
TI  - DTAF dye concentrations commonly used to measure microscale deformations in
      biological tissues alter tissue mechanics.
AB  - Identification of the deformation mechanisms and specific components underlying
      the mechanical function of biological tissues requires mechanical testing at
      multiple levels within the tissue hierarchical structure.
      Dichlorotriazinylaminofluorescein (DTAF) is a fluorescent dye that is used to
      visualize microscale deformations of the extracellular matrix in soft collagenous
      tissues. However, the DTAF concentrations commonly employed in previous
      multiscale experiments (>=2000 ug/ml) may alter tissue mechanics. The objective
      of this study was to determine whether DTAF affects tendon fascicle mechanics and
      if a concentration threshold exists below which any observed effects are
      negligible. This information is valuable for guiding the continued use of this
      fluorescent dye in future experiments and for interpreting the results of
      previous work. Incremental strain testing demonstrated that high DTAF
      concentrations (>=100 ug/ml) increase the quasi-static modulus and yield strength
      of rat tail tendon fascicles while reducing their viscoelastic behavior.
      Subsequent multiscale testing and modeling suggests that these effects are due to
      a stiffening of the collagen fibrils and strengthening of the interfibrillar
      matrix. Despite these changes in tissue behavior, the fundamental deformation
      mechanisms underlying fascicle mechanics appear to remain intact, which suggests
      that conclusions from previous multiscale investigations of strain transfer are
      still valid. The effects of lower DTAF concentrations (<=10 ug/ml) on tendon
      mechanics were substantially smaller and potentially negligible; nevertheless, no
      concentration was found that did not at least slightly alter the tissue behavior.
      Therefore, future studies should either reduce DTAF concentrations as much as
      possible or use other dyes/techniques for measuring microscale deformations. 

PMID- 24915575
TI  - Manipulation of silver nanocubes detection sensitivity to radical compounds by
      modifying their surfaces with anionic/cationic polyelectrolytes for wide-range
      quantification of radicals.
AB  - We report a method for controlling the detection sensitivity to or the degree of
      etching of Ag nanocubes by radicals by modifying their surfaces with poly(acrylic
      acid) or poly(allylamine hydrochloride) for wide-range quantification of radical
      compounds. The degree of Ag nanocube etching is influenced by the concentrations
      of the polyelectrolytes used for modification. These polyelectrolytes protect the
      Ag nanocubes, probably by either retarding (forming diffusion barriers) or
      preventing (blocking/entrapping/scavenging) the arrival of radicals to Ag
      nanocubes, or both. The weights of the two roles are different depending on the
      polyelectrolyte type; therefore, the sensitivities of Ag nanocubes are also
      influenced by this factor. The roles of the polyelectrolytes were demonstrated by
      using radical compounds produced from tetrahydrofuran and H2O2 and further
      confirmed with Ag nanospheres. Using the results, the radical sensitivities and
      detection ranges of polyelectrolyte-modified Ag nanoparticles could be
      manipulated. Moreover, we produced calibration curves for the wide-range
      quantification of radical compounds. 

PMID- 24915573
TI  - Intraluminal administration of poly I:C causes an enteropathy that is exacerbated
      by administration of oral dietary antigen.
AB  - Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics
      virally-induced activation of TLR3 signalling causing acute small intestine
      damage, but whether and how mucosal administration of poly I:C causes enteropathy
      is less clear. Our aim was to investigate the inflammatory pathways elicited
      after intraluminal administration of poly I:C and determine acute and delayed
      consequences of this locally induced immune activation. Intraluminal poly I:C
      induced rapid mucosal immune activation in C57BL/6 mice involving IFNbeta and the
      CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile.
      Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin
      sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration
      of gliadin. Our results indicate that small intestine pathology can be induced in
      mice by intraluminal administration of poly I:C and that this is exacerbated by
      subsequent oral delivery of a relevant dietary antigen. 

PMID- 24915576
TI  - Layered inorganic solids.

PMID- 24915574
TI  - Exendin-4 pretreated adipose derived stem cells are resistant to oxidative stress
      and improve cardiac performance via enhanced adhesion in the infarcted heart.
AB  - Reactive oxygen species (ROS), which were largely generated after myocardial
      ischemia, severely impaired the adhesion and survival of transplanted stem cells.
      In this study, we aimed to determine whether Exendin-4 pretreatment could improve
      the adhesion and therapeutic efficacy of transplanted adipose derived stem cells
      (ADSCs) in ischemic myocardium. In vitro, H2O2 was used to provide ROS
      environments, in which ADSCs pretreated with Exendin-4 were incubated. ADSCs
      without pretreatment were used as control. Then, cell adhesion and viability were
      analyzed with time. Compared with control ADSCs, Exendin-4 treatment
      significantly increased the adhesion of ADSCs in ROS environment, while reduced
      intracellular ROS and cell injury as determined by dihydroethidium (DHE) staining
      live/Dead staining, lactate dehydrogenase-release assay and MTT assay. Western
      Blotting demonstrated that ROS significantly decreased the expression of adhesion
      related integrins and integrin-related focal adhesion proteins, which were
      significantly reversed by Exendin-4 pretreatment and followed by decreases in
      caspase-3, indicating that Exendin-4 may facilitate cell survival through
      enhanced adhesion. In vivo, myocardial infarction (MI) was induced by the left
      anterior descending artery ligation in SD rats. Autologous ADSCs with or without
      Exendin-4 pretreatment were injected into the border area of infarcted hearts,
      respectively. Multi-techniques were used to assess the beneficial effects after
      transplantation. Longitudinal bioluminescence imaging and histological staining
      revealed that Exendin-4 pretreatment enhanced the survival and differentiation of
      engrafted ADSCs in ischemic myocardium, accompanied with significant benefits in
      cardiac function, matrix remodeling, and angiogenesis compared with non
      pretreated ADSCs 4 weeks post-transplantation. In conclusion, transplantation of
      Exendin-4 pretreated ADSCs significantly improved cardiac performance and can be
      an innovative approach in the clinical perspective. 

PMID- 24915577
TI  - A hydrophobic disordered peptide spontaneously anchors a covalently bound RNA
      hairpin to giant lipidic vesicles.
AB  - The attraction of nucleic acids to lipidic compartments is the first step for
      carriers of potentially inheritable information to self-organise in
      functionalised synthetic cells. Confocal fluorescence imaging shows that a
      synthetic amphiphilic peptidyl RNA molecule spontaneously accumulates at the
      outer bilayer membranes of phospho- and glycolipidic giant vesicles.
      Cooperatively attractive interactions of -3.4 to -4.0 kcal mol(-1) between a
      random coil hydrophobic peptide and lipid membranes can thus pilot lipophobic RNA
      to its compartmentation. The separation of mixed lipid phases in the membranes
      further enhances the local concentration of anchored RNA. 

PMID- 24915578
TI  - Role of aggregation in the synthesis and polymerization activity of SalBinap
      indium alkoxide complexes.
AB  - The reaction of racemic SalBinap ligand, (+/-)-H2(ONN*OMe), with InCl3 and excess
      NaOEt generated a mixture of two dinuclear compounds [(MU-kappa(2)-ONN*OMe)In(MU
      OEt)]2 (1a) and [kappa(4)-ONN*OMe)In(MU-OEt)]2 (1b), which were isolated and
      fully characterized. Polymerization of racemic lactide with 1a and 1b was slow in
      refluxing THF and showed only modest stereoselectivity. Catalyst 1b displayed
      better control than 1a, with the experimental molecular weights of the resulting
      poly(lactic acid) in agreement with the expected values. The higher-than-expected
      molecular weights observed in polymers formed by 1a were due to partial
      initiation of the catalyst. The reaction of (+/-)-H2(ONN*OtBu) with InCl3 yielded
      (kappa(4)-ONN*OtBu)InCl (2); however, further reactivity of the compound formed a
      mixture of products. An attempt to prevent aggregation by reacting (+/-)
      H2(ONN*OMe) with InCl3 and excess NaO(i)Pr yielded an intractable mixture,
      including [(MU-kappa(2)-ONN*OMe)In]2(MU-Cl)(MU-OH) (3). The thermal stabilities
      of compounds 1a and 1b under polymerization conditions were investigated.
      Examination of the polymerization behavior of complexes 1a and 1b and the
      reaction equilibrium between the two illustrates the importance of aggregation in
      indium salen complexes compared to their aluminum counterparts. 

PMID- 24915579
TI  - IGF2BP1 expression in human mesenchymal stem cells significantly affects their
      proliferation and is under the epigenetic control of TET1/2 demethylases.
AB  - Mesenchymal stem cells (MSCs) are a population of cells harboring in many tissues
      with the ability to differentiate toward many different lineages. Unraveling the
      molecular profile of MSCs is of great importance due to the fact that these cells
      are very often used in preclinical and clinical studies. We have previously
      reported the expression of insulin-like growth factor 2 mRNA binding protein 1
      (IGF2BP1) an oncofetal mRNA-binding protein-in different stem cell types such as
      bone marrow (BM)-MSC and umbilical cord blood (UCB)-hematopoietic stem cells.
      Here, we demonstrate that MSCs of adipose tissue, BM, and UC origin have a
      differential pattern of IGF2BP1 and ten-eleven-translocate 1/2 (TET1/2)
      expression that could correlate with their proliferation potential. Upon IGF2BP1
      interference, a significant reduction of cell proliferation is observed,
      accompanied by reduced expression of c-MYC and GLI1 and increased p21. We also
      present, for the first time, evidence that IGF2BP1 is epigenetically regulated by
      TET1 and TET2 demethylases. Specifically, we show that TET1 directly binds to the
      promoter of IGF2BP1 gene and affects the hydroxymethylation status of its
      promoter. These results indicate that IGF2BP1 and TET1/2 contribute to the
      stemness of MSCs, at least regarding their proliferative potential. 

PMID- 24915580
TI  - Grainyhead-like 3 regulation of endothelin-1 in the pharyngeal endoderm is
      critical for growth and development of the craniofacial skeleton.
AB  - Craniofacial development is a highly conserved process that requires complex
      interactions between neural crest cells (NCCs) and pharyngeal tissues derived
      from all three germ layers. Signals emanating from the pharyngeal endoderm drive
      differentiation of NCCs into craniofacial cartilage, and disruption of this
      process underpins several human craniofacial defects (CFD). Here, we demonstrate
      that morpholino (MO)-mediated knockdown in zebrafish of the highly conserved
      transcription factor grainyhead-like 3 (grhl3), which is selectively expressed in
      the pharyngeal endoderm, leads to severe hypoplasia of the lower jaw cartilages.
      Phylogenetic analysis of conserved grhl-binding sites in gene regulatory regions
      identified endothelin-1 (edn1) as a putative direct grhl3 target gene, and this
      was confirmed by chromatin precipitation (ChIP) assays in zebrafish embryos.
      Injection of sub-phenotypic concentrations of MOs targeting both grhl3 and edn1
      induced jaw abnormalities, and injection of edn1 mRNA into grhl3-morphants
      rescued both pharyngeal expression of the downstream effectors of edn1, and jaw
      cartilage formation. This study sheds new light on the role of endodermal
      endothelin-1 in vertebrate jaw development, and highlights potential new genetic
      defects that could underpin human CFD. 

PMID- 24915581
TI  - Automated versus non-automated weaning for reducing the duration of mechanical
      ventilation for critically ill adults and children.
AB  - BACKGROUND: Automated closed loop systems may improve adaptation of mechanical
      support for a patient's ventilatory needs and facilitate systematic and early
      recognition of their ability to breathe spontaneously and the potential for
      discontinuation of ventilation. This review was originally published in 2013 with
      an update published in 2014. OBJECTIVES: The primary objective for this review
      was to compare the total duration of weaning from mechanical ventilation, defined
      as the time from study randomization to successful extubation (as defined by
      study authors), for critically ill ventilated patients managed with an automated
      weaning system versus no automated weaning system (usual care).Secondary
      objectives for this review were to determine differences in the duration of
      ventilation, intensive care unit (ICU) and hospital lengths of stay (LOS),
      mortality, and adverse events related to early or delayed extubation with the use
      of automated weaning systems compared to weaning in the absence of an automated
      weaning system. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE
      (OvidSP) (1948 to September 2013); EMBASE (OvidSP) (1980 to September 2013);
      CINAHL (EBSCOhost) (1982 to September 2013); and the Latin American and Caribbean
      Health Sciences Literature (LILACS). Relevant published reviews were sought using
      the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology
      Assessment Database (HTA Database). We also searched the Web of Science
      Proceedings; conference proceedings; trial registration websites; and reference
      lists of relevant articles. The original search was run in August 2011, with
      database auto-alerts up to August 2012. SELECTION CRITERIA: We included
      randomized controlled trials comparing automated closed loop ventilator
      applications to non-automated weaning strategies including non-protocolized usual
      care and protocolized weaning in patients over four weeks of age receiving
      invasive mechanical ventilation in an ICU. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted study data and assessed risk of bias. We combined
      data in forest plots using random-effects modelling. Subgroup and sensitivity
      analyses were conducted according to a priori criteria. MAIN RESULTS: We included
      21 trials (19 adult, two paediatric) totaling 1676 participants (1628 adults, 48
      children) in this updated review. Pooled data from 16 eligible trials reporting
      weaning duration indicated that automated closed loop systems reduced the
      geometric mean duration of weaning by 30% (95% confidence interval (CI) 13% to
      45%), however heterogeneity was substantial (I(2) = 87%, P < 0.00001). Reduced
      weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10%
      to 63%) and Smartcare/PSTM (28%, 95% CI 7% to 49%) but not in surgical
      populations or using other systems. Automated closed loop systems reduced the
      duration of ventilation (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to
      15%). There was no strong evidence of an effect on mortality rates, hospital LOS,
      reintubation rates, self-extubation and use of non-invasive ventilation following
      extubation. Prolonged mechanical ventilation > 21 days and tracheostomy were
      reduced in favour of automated systems (relative risk (RR) 0.51, 95% CI 0.27 to
      0.95 and RR 0.67, 95% CI 0.50 to 0.90 respectively). Overall the quality of the
      evidence was high with the majority of trials rated as low risk. AUTHORS'
      CONCLUSIONS: Automated closed loop systems may result in reduced duration of
      weaning, ventilation and ICU stay. Reductions are more likely to occur in mixed
      or medical ICU populations. Due to the lack of, or limited, evidence on automated
      systems other than Smartcare/PSTM and Adaptive Support Ventilation no conclusions
      can be drawn regarding their influence on these outcomes. Due to substantial
      heterogeneity in trials there is a need for an adequately powered, high quality,
      multi-centre randomized controlled trial in adults that excludes 'simple to wean'
      patients. There is a pressing need for further technological development and
      research in the paediatric population.

PMID- 24915582
TI  - Drug-coated balloons vs. drug-eluting stents for treatment of long
      femoropopliteal lesions.
AB  - PURPOSE: To compare the performance of drug-coated balloons (DCB) and drug
      eluting stents (DES) in long femoropopliteal lesions. METHODS: A retrospective
      dual center study included 228 patients (139 men; median age 69 years) with
      femoropopliteal lesions >=10 cm suffering from peripheral artery disease
      (Rutherford categories 1-5) treated either with DCB or DES. Propensity score
      stratification was used to minimize bias. The 131 DCB patients (77 men; mean age
      68.9+/-10.5 years) had a mean lesion length of 194.4+/-86.3 mm (range 100-450),
      while the 97 DES patients (62 men; mean age 68.2+/-8.0 years) had lesions
      averaging 195.0+/-64.5 mm (range 100-350) in length. Restenotic lesions were
      treated in 68 (51.9%) DCB patients and 43 (44.3%) DES patients; over half the
      lesions in both groups were total occlusions [DCB: 69 (52.7%), DES: 61 (62.9%)].
      Outcome measures were patency (peak systolic velocity ratio <2.4), clinically
      driven target lesion revascularization (TLR), event-free survival, and freedom
      from worsening of Rutherford classification by >=2 categories. RESULTS: In the
      DCB cohort, provisional stent placement was performed in 24 (18.3%) lesions for
      refractory stenosis (5, 3.8%), flow-limiting dissection (13, 9.9%), and other
      reasons (6, 4.6%). There was no procedure-related mortality in either cohort. The
      binary restenosis rates were 23.9% (26/109) and 30.4% (24/79, p=0.319) in the DCB
      and DES cohorts, respectively, and clinically driven TLR rates were 15.6%
      (17/109) vs. 19.0% (15/79, p=0.543), respectively. Estimates for freedom from
      clinically driven TLR and event-free survival were not different between the
      study cohorts nor were outcomes regarding the ankle-brachial index and Rutherford
      category. CONCLUSION: DCB and DES perform equally well in the endovascular
      treatment of femoropopliteal lesions >=10 cm and better than traditional
      endovascular treatment. In a real world setting of TASC C and D lesions, the
      provisional stent rate in the DCB cohort is low.

PMID- 24915583
TI  - Commentary: comparative effectiveness of paclitaxel-based femoropopliteal
      interventions.

PMID- 24915584
TI  - PEACE I all-comers registry: patency evaluation after implantation of the 4
      French Pulsar-18 self-expanding nitinol stent in femoropopliteal lesions.
AB  - PURPOSE: To evaluate the 1-year patency of the 4-F Pulsar-18 self-expanding
      nitinol stent for treatment of femoropopliteal occlusive disease in a national,
      prospective, multicenter, all-comers registry. METHODS: Between January and June
      2012, the German PEACE I all-comers prospective registry enrolled 148 patients
      with symptomatic femoropopliteal lesions (Rutherford category 2-5) undergoing
      recanalization and implantation of the Pulsar-18 SE nitinol stent at 6 clinical
      centers. Thirty patients did not have the 12-month follow-up visit (18 declined
      reevaluation, 5 withdrew consent, and 7 died), leaving 118 patients (64 men; mean
      71.9+/-9.6 age years) for the 1-year evaluation. The average lesion length was
      111.5+/-71.4 mm, and 38 of the 118 lesions were classified as TASC II D. More
      than half the lesions (67, 56.7%) were chronic total occlusions (CTO). The
      popliteal segment was involved in 22 (18.7%) lesions. The mean stented length was
      122.7+/-64.5 mm. Routine follow-up included duplex ultrasound at 6 and 12 months.
      Outcome measures were primary patency and no clinically driven target lesion
      revascularization (TLR) within 12 months. RESULTS: The overall primary patency
      rates after 6 and 12 months were 87.4% and 79.5%, respectively; in the popliteal
      segments, the rate was 71.4% after 12 months. The overall freedom from TLR was
      93.2% after 6 months and 81% after 12 months. Ankle-brachial index, pain-free
      walking distance, and Rutherford category all improved significantly (p<0.0001)
      after 6 and 12 months. The primary patency rates in patients with diabetes
      (p=1.0) and those with renal insufficiency (p=0.8) were not significantly lower
      compared to the overall rate. There was no significant difference (p=0.67) in
      restenosis rate for recanalization of CTOs compared to non-CTO lesions.
      CONCLUSIONS: In this all-comers registry, the use of the Pulsar-18 self-expanding
      nitinol stent in femoropopliteal lesions averaging 111.5 mm long showed promising
      primary patency and freedom from TLR after 6 and 12 months. Diabetes had no
      negative impact on patency. Primary patency in the popliteal segments was
      acceptable at 12 months.

PMID- 24915585
TI  - Five-year prognosis after endovascular therapy in claudicant patients with
      iliofemoral artery disease.
AB  - PURPOSE: To examine the prognosis of patients with intermittent claudication who
      received treatment with endovascular techniques. METHODS: A retrospective
      multicenter study was performed involving 2930 consecutive patients (2307 men;
      mean age 71.5+/-8.9 years) with intermittent claudication who underwent an
      endovascular procedure for a de novo iliofemoral artery lesion. The primary
      outcome measure was overall survival. The secondary outcomes were freedom from
      major adverse cardiovascular events (MACE: all-cause death, myocardial
      infarction, and stroke) and from major adverse cardiovascular and limb events
      (MACE with repeat revascularization or above-knee amputation of the target limb).
      Cox multivariate regression analysis of selected baseline characteristics,
      procedure-related complications, and medication use was performed to determine
      predictors for all-cause mortality. Positive predictors from this analysis were
      used to stratify patients into low- (1410, 48.1%), moderate- (1406, 48.0%), and
      high-risk (114, 3.9%) categories. RESULTS: The overall survival rates were 97.2%,
      90.8%, and 83.4% at 1, 3, and 5 years, respectively. The cause of death was
      cardiovascular in 42.8% of cases. Freedom from MACE was 96.7%, 88.6%, and 77.3%
      at 1, 3, and 5 years, respectively. Cox multivariate regression analysis
      identified age, dialysis, left ventricular dysfunction, insulin-dependent
      diabetes, hematoma prolonging hospitalization, coronary artery disease, and
      superficial femoral plus iliac lesions as positive predictors of all-cause
      mortality. In the risk stratification analysis, the overall 5-year survival rate
      was significantly lower in high-risk patients compared to the other groups (90.1%
      vs. 78.6% vs. 53.5%, p<0.0001). CONCLUSION: The prognosis in patients with
      intermittent claudication after endovascular therapy was relatively good but
      extremely poor for the high-risk patient subgroup.

PMID- 24915586
TI  - Commentary: endovascular therapy for intermittent claudication: is it time for re
      evaluation?

PMID- 24915587
TI  - Feasibility of endovascular recanalization of occluded infrapopliteal drug
      eluting stents.
AB  - PURPOSE: To investigate the safety and feasibility of percutaneous endovascular
      recanalization of late total occlusions of infrapopliteal drug-eluting stents
      (DES). METHODS: A retrospective study investigated all 408 infrapopliteal stent
      procedures performed in 367 patients between January 2007 and October 2013 to
      identify those who underwent percutaneous reintervention for symptomatic
      infrapopliteal balloon-expandable DES occlusion. The search identified 49
      patients with at least one infrapopliteal DES occlusion in 61 (14.9%) of 408
      limbs. Seven (14.3%) patients were excluded from the analysis owing to
      asymptomatic status (n=6) and acute thrombotic occlusion (n=1), leaving 42
      patients who underwent endovascular revascularization of occluded stents in 54
      limbs. The study's primary outcomes were technical success and complication rates
      of endovascular recanalization, while secondary outcomes included limb salvage
      and the identification of factors influencing primary results. RESULTS: Technical
      success was 90.7% (49/54 procedures). Technical failure was seen only in cases of
      stent collapse and overlapping native popliteal artery-infrapopliteal stent
      occlusion. According to Kaplan-Meier analysis, survival was 89.6%, 81.1%, and
      73.5% at 1, 2, and 3 years, respectively, while limb salvage rates were 86.1%,
      79.3%, and 72.7% at the same time points. There was 1 (1.8%) case of distal
      embolization. No factors influencing outcomes could be identified. CONCLUSION:
      Percutaneous recanalization of infrapopliteal stent total occlusions is safe and
      feasible. Technical failure was noted in cases of stent deformation occurring at
      the pedal artery and in overlapping native popliteal artery-infrapopliteal stent
      occlusion.

PMID- 24915589
TI  - Commentary: endovascular treatment for buttock claudication: the proof of the
      pudding is in the eating!

PMID- 24915588
TI  - Angioplasty of the superior gluteal artery in 34 patients with buttock
      claudication.
AB  - PURPOSE: To evaluate the performance of balloon angioplasty in the treatment of
      superior gluteal artery (SGA) lesions and the factors influencing results.
      METHODS: Between April 1997 and June 2012, 217 patients were treated for
      disabling buttock claudication. Of these, 34 (15%) consecutive patients (30 men;
      mean age 70+/-9 years) underwent angioplasty for 44 SGA origin lesions (5
      bilateral): 24 stenoses and 20 occlusions. Standardized follow-up included
      clinical examination at 1 and 6 months and annually thereafter; angiography or
      computed tomography was obtained in cases of recurrent buttock claudication.
      RESULTS: Angioplasty was successful in 31 patients; 3 of the 20 SGA occlusions
      could not be recanalized. Twenty-four (59%) SGAs were treated without a stent (14
      stenoses and 10 occlusions), while 10 stenoses and 7 occlusions were stented.
      There were no instances of SGA rupture, occlusion, or pseudoaneurysm. Two
      recanalizations were complicated with contrast extravasation in the buttock
      without consequence. Over a mean 49.8+/-39 months (range 1-132), 5 patients died
      of unrelated causes. Buttock claudication recurred in 13 (38%) patients (14 SGA
      lesions) at a mean 21.5+/-14 months (range 1-132); repeat angioplasty was
      successful in 8 patients. Estimates of primary and secondary freedom from symptom
      recurrence at 4 years were 60% and 68%, respectively. There was no difference in
      patency between SGAs treated for occlusion or stenosis or between those treated
      with or without a stent. CONCLUSION: In this series, angioplasty has proven to be
      a safe and efficacious way to treat SGA lesions with disabling claudication.
      Repeat balloon dilation was effective in treating SGA restenosis but failed in
      three quarters of the reocclusions. Progress in guidewire design and optimal use
      has improved success with SGA occlusions.

PMID- 24915590
TI  - Endovascular treatment of persistent sciatic artery aneurysm with the multilayer
      stent.
AB  - PURPOSE: To describe the successful management of a symptomatic persistent
      sciatic artery (PSA) aneurysm using the Multilayer Aneurysm Repair System (MARS).
      CASE REPORT: A 50-year-old man with history of smoking, hypertension, and
      hypercholesterolemia suddenly developed pain in the buttock radiating to the left
      lower limb, mimicking sciatica. The ~57*54-mm incomplete type PSA aneurysm was
      treated with two 14*80- and 14*60-mm MARS devices through a surgical left
      axillary artery access. There were no periprocedural complications. Thirty-day
      imaging documented patency of the stents and a minor reduction (~47*55 mm) in the
      aneurysm, with slightly hyperdense content and no signs of perfusion. At 6
      months, duplex and computed tomographic angiography showed complete thrombosis of
      the sac, patency of the multilayer stents, and further aneurysm shrinkage (40*37
      mm). CONCLUSION: The multilayer stent can alter the hemodynamics inside a
      peripheral aneurysm to promote sac thrombosis and redirect flow to collaterals
      originating from the sac.

PMID- 24915591
TI  - Commentary: endovascular treatment of persistent sciatic artery aneurysm with the
      multilayer stent: is it a miraculous solution for all complex conditions?

PMID- 24915592
TI  - Transvascular autonomic modulation: a modified balloon angioplasty technique for
      the treatment of autonomic dysfunction in multiple sclerosis patients.
AB  - PURPOSE: To describe the use of transvascular autonomic modulation (TVAM) to
      improve cardiovascular autonomic nervous system (ANS) dysfunction in multiple
      sclerosis (MS) patients, comparing the safety and efficacy of this modified
      technique with traditional balloon angioplasty. METHODS: Twenty-one MS patients
      (11 men; mean age 48.7+/-13.0 years) who presented with symptoms of
      cardiovascular ANS dysfunction underwent TVAM. These patients were compared with
      age/sex-matched MS patients (10 men; 49.3+/-11.1 years) in the same stages of the
      disease who presented with chronic cerebrospinal venous insufficiency (CCSVI) and
      who underwent venous balloon angioplasty. TVAM involved the coupling of balloon
      angioplasty of the internal jugular veins with the application of external manual
      compression and dilation of the azygos and renal veins; unlike traditional
      angioplasty for CCSVI, which treats only abnormal veins (>=50% stenosis or static
      valve), all targeted vessels were treated with TVAM regardless of the presence of
      an abnormality. The effect of TVAM on ANS function was indicated by determining
      heart rate variability based on the electrocardiographic R-R interval lengths
      using vector analysis to derive the mean circular resultant (MCR) and the
      expiration/inspiration (E/I) ratio, the Valsalva ratio, and the 30:15 postural
      ratio at 24 hours after intervention. RESULTS: Left renal vein compression was
      common among the TVAM patients and resulted in >=50% luminal compromise in 10 of
      21 patients. Azygos vein abnormalities (a static valve) were identified in 5
      patients. Overall, 18 patients met the diagnostic criteria for CCSVI with at
      least one lesion >50%, but only 10 lesions were considered treatable by
      traditional balloon angioplasty. After intervention, the R-R interval values,
      including the 30:15 postural ratio (p=0.01), the MCR (p=0.1), and E/I ratio
      (p=0.1), were higher for the TVAM patients compared to the control group. The
      safety profile of the TVAM procedure was similar to that of traditional balloon
      angioplasty. CONCLUSION: The combination of balloon angioplasty of anatomically
      normal veins coupled with external compression during dilation of these veins can
      improve indicators of ANS dysfunction. The safety and efficacy of TVAM in MS
      patients observed in this pilot study is encouraging, paving the way for the
      treatment of dysautonomia in pathological states other than MS. Further studies
      should investigate TVAM in a larger MS cohort.

PMID- 24915593
TI  - Histological observations one year after mechanochemical endovenous ablation of
      the great saphenous vein.
AB  - PURPOSE: To report histological analysis of a great saphenous vein (GSV) 1 year
      after undergoing mechanochemical endovenous ablation (MOCA) and compare the
      findings with those of a healthy vein. CASE REPORT: A 59-year-old patient with
      bilateral GSV incompetence was treated with MOCA using the ClariVein catheter,
      which has a dispersion wire that rotates as liquid sclerosant is injected in the
      vein. After 1 year, the patient had recurrent edema of the right leg; duplex
      ultrasound was suspicious for recanalization. The patient was reoperated, and the
      deep femoral vein was explored. The GSV was completely obliterated, and its
      proximal part was excised and sent for histological processing. Microscopic
      evaluation of the MOCA-treated vein showed a circumferential disappearance of the
      endothelial layer and fibrosis of the vein. The media was considerably damaged,
      with changes in collagen structure, supporting the therapeutic effect of MOCA.
      CONCLUSION: MOCA is a novel endovenous treatment modality for saphenous vein
      insufficiency. Results of MOCA on the cellular level are essential to optimize
      treatment.

PMID- 24915594
TI  - Applying findings of computational studies in vascular clinical practice: fact,
      fiction, or misunderstanding?

PMID- 24915595
TI  - Abdominal aortic endografting beyond the trials: a 15-year single-center
      experience comparing newer to older generation stent-grafts.
AB  - PURPOSE: To evaluate the late results of endovascular aneurysm repair (EVAR) with
      the endografts currently in use and compare outcomes to older devices. METHODS:
      Clinical, demographic, and imaging data on consecutive patients undergoing
      elective EVAR from January 1997 to December 2011 at a single center were
      retrieved from an electronic database and reviewed. Newer stent-grafts (NSG) were
      defined as those introduced after 2004 (second-generation Excluder and Anaconda)
      or currently in use without modifications (Zenith, Endurant). Of the 1412
      consecutive patients (1290 men; mean age 73 years) who underwent elective EVAR in
      a tertiary university hospital, 882 were treated with NSGs and 530 with older
      stent-grafts (OSGs). RESULTS: In the NSG group, the abdominal aortic aneurysms
      (AAA) were larger (55.7 vs. 53.2 mm, p<0.0001) and the patients were older
      (p<0.0001) and less frequently smokers or had pulmonary disease, while
      hypertension and diabetes were more frequent (all p<0.0001). Thirty-day mortality
      was 0.8% in the NSG group vs. 1.1% in the OSG group (p=NS). Follow-up ranged from
      1 to 174 months (mean 54.1+/-42.4); the OSG patients had longer mean follow-up
      compared to the NSG group (80.2+/-47.9 vs. 38.4+/-29.1 months, p<0.0001). All
      cause survival rates were comparable in both groups. Freedom from late conversion
      (96.1% vs. 89.1% at 7 years, p<0.0001) or reintervention (83.6% vs. 74.2% at 7
      years, p=0.015) and freedom from AAA diameter growth >5 mm (p=0.022) were higher
      in the NSG group. In adjusted analyses, the use of a new-generation device was a
      negative independent predictor of reintervention [hazard ratio (HR) 0.67, 95%
      confidence interval (CI) 0.49 to 0.93, p=0.015] and aneurysm growth (HR 0.63, 95%
      CI 0.45 to 0.89, p=0.010). CONCLUSION: Newer-generation endografts can perform
      substantially better than the older devices. In the long term, incidences of
      reintervention, conversion, and AAA growth are decreased in patients treated with
      devices currently in use. However, the need for continuous surveillance is still
      imperative for all endografts.

PMID- 24915596
TI  - Outcome after preservation of infected abdominal aortic endografts.
AB  - PURPOSE: To review the published outcomes of aortic endograft infection treated
      with preservation of the stent-graft. METHODS: An extensive electronic health
      database search was undertaken to identify all articles published up to May 2013
      that reported endograft infection after endovascular aneurysm repair (EVAR) in
      which treatment included preservation of the stent-graft. The search found 17
      articles with 29 patients (27 men; mean age 73.1+/-7.6 years) fulfilling the
      inclusion criteria. RESULTS: In 2 (7%) cases, the endograft infection was
      diagnosed within 30 days of the initial procedure; 4 (14%) were identified within
      3 months and the remaining 23 (79%) within 12 months. Staphylococcus species,
      Streptococcus species, and Escherichia coli were the most common isolated
      microorganisms. Seven (24%) had a secondary aortoenteric fistula after EVAR.
      Twelve (41%) patients received only antibiotic therapy, while the remaining had
      an additional procedure (drainage, surgical debridement, sac irrigation, and/or
      omentoplasty). The in-hospital mortality was 21% (n=6). During a mean follow-up
      of 11.4+/-3.1 months, 7 more patients died (overall mortality 45%). None of the 7
      patients with fistula survived. Half (50%) of the 12 patients who received only
      antibiotic therapy died, while 7 (41%) of the 17 patients who underwent an
      additional procedure died during follow-up. CONCLUSION: Among patients treated
      for endograft infection without explantation, those with aortoenteric fistula had
      the worst outcome. There is evidence for lower mortality in patients who
      underwent an additional procedure, such as drainage, surgical debridement, and
      sac irrigation. Larger studies are needed to examine the efficacy of this
      approach compared to surgical conversion with endograft excision and in situ
      reconstruction or extra-anatomical bypass.

PMID- 24915597
TI  - Optical frequency-domain imaging to guide implantation of a paclitaxel-eluting
      stent in the femoral artery.

PMID- 24915598
TI  - Re: "a novel cautery instrument for on-site fenestration of aortic stent-grafts:
      a feasibility study of 18 patients".

PMID- 24915600
TI  - Inversion of lithium heparin gel tubes after centrifugation is a significant
      source of bias in clinical chemistry testing.
AB  - BACKGROUND: This study was planned to establish whether random orientation of gel
      tubes after centrifugation may impair sample quality. MATERIALS AND METHODS:
      Eight gel tubes were collected from 17 volunteers: 2 Becton Dickinson (BD) serum
      tubes, 2 Terumo serum tubes, 2 BD lithium heparin tubes and 2 Terumo lithium
      heparin tubes. One patient's tube for each category was kept in a vertical,
      closure-up position for 90 min ("upright"), whereas paired tubes underwent bottom
      up inversion every 15 min, for 90 min ("inverted"). Immediately after this period
      of time, 14 clinical chemistry analytes, serum indices and complete blood count
      were then assessed in all tubes. RESULTS: Significant increases were found for
      phosphate and lipaemic index in all inverted tubes, along with AST, calcium,
      cholesterol, LDH, potassium, hemolysis index, leukocytes, erythrocytes and
      platelets limited to lithium heparin tubes. The desirable quality specifications
      were exceeded for AST, LDH, and potassium in inverted lithium heparin tubes.
      Residual leukocytes, erythrocytes, platelets and cellular debris were also
      significantly increased in inverted lithium heparin tubes. CONCLUSIONS: Lithium
      heparin gel tubes should be maintained in a vertical, closure-up position after
      centrifugation.

PMID- 24915601
TI  - Evaluation of damaging effects of splicing mutations: validation of an in vitro
      method for diagnostic laboratories.
AB  - BACKGROUND: Pre-mRNA splicing defects may have an important impact on clinical
      phenotype in several diseases, but often their pathogenic role is difficult to
      demonstrate. The aim of this study was to validate an in vitro method to assess
      the effects of putative splicing variants. MATERIALS AND METHODS: We studied
      three novel variants in vitro using a novel minigene approach and compared
      results with in silico and ex vivo strategies from patient samples. RESULTS: For
      the c.1146C>T variant in the LMNA gene, in vitro and ex vivo studies were
      concordant with the prediction obtained by in silico tools, confirming the loss
      of 13 bp at the end of exon 6. In the second case (c.1140+1G>A, SCN5A gene), in
      vitro experiments identified the insertion of 94 intronic bp in exon 9 as well as
      exon 9 skipping, but these results were not correctly predicted by ex vivo data
      and in silico tools. In the third case (c.1608+1C>T, LMNA gene) in vitro and ex
      vivo studies suggested the recognition of an exonic cryptic site leading to the
      loss of 29 bp in exon 9, not predicted by in silico analysis. CONCLUSION: Our
      results revealed how in silico tools are often unreliable requiring "wet" RNA
      analysis. Since ex vivo studies are not always feasible, the use of an in vitro
      construct represents an efficient and useful method for the evaluation of
      damaging effects of unknown splicing variants, especially in diagnostic
      laboratories.

PMID- 24915599
TI  - TRP channel cannabinoid receptors in skin sensation, homeostasis, and
      inflammation.
AB  - In the skin, cannabinoid lipids, whether of endogenous or exogenous origin, are
      capable of regulating numerous sensory, homeostatic, and inflammatory events.
      Although many of these effects are mediated by metabotropic cannabinoid
      receptors, a growing body of evidence has revealed that multiple members of the
      transient receptor potential (TRP) ion channel family can act as "ionotropic
      cannabinoid receptors". Furthermore, many of these same TRP channels are
      intimately involved in cutaneous processes that include the initiation of pain,
      temperature, and itch perception, the maintenance of epidermal homeostasis, the
      regulation of hair follicles and sebaceous glands, and the modulation of
      dermatitis. Ionotropic cannabinoid receptors therefore represent potentially
      attractive targets for the therapeutic use of cannabinoids to treat sensory and
      dermatological diseases. Furthermore, the interactions between neurons and other
      cell types that are mediated by cutaneous ionotropic cannabinoid receptors are
      likely to be recapitulated during physiological and pathophysiological processes
      in the central nervous system and elsewhere, making the skin an ideal setting in
      which to dissect general complexities of cannabinoid signaling.

PMID- 24915602
TI  - Method of continuous variation: characterization of alkali metal enolates using
      1H and 19F NMR spectroscopies.
AB  - The method of continuous variation in conjunction with (1)H and (19)F NMR
      spectroscopies was used to characterize lithium and sodium enolates solvated by
      N,N,N',N'-tetramethylethyldiamine (TMEDA) and tetrahydrofuran (THF). A strategy
      developed using lithium enolates was then applied to the more challenging sodium
      enolates. A number of sodium enolates solvated by TMEDA or THF afford exclusively
      tetramers. Evidence suggests that TMEDA chelates sodium on cubic tetramers. 

PMID- 24915604
TI  - Stimulating nitrate removal processes of restored wetlands.
AB  - The environmental and health effects caused by nitrate contamination of aquatic
      systems are a serious problem throughout the world. A strategy proposed to
      address nitrate pollution is the restoration of wetlands. However, although
      natural wetlands often remove nitrate via high rates of denitrification, wetlands
      restored for water quality functions often fall below expectations. This may be
      in part because key drivers for denitrification, in particular soil carbon, are
      slow to develop in restored wetlands. We added organic soil amendments that range
      along a gradient of carbon lability to four newly restored wetlands in western
      New York to investigate the effect of carbon additions on denitrification and
      other processes of the nitrogen cycle. Soil carbon increased by 12.67-63.30% with
      the use of soil amendments (p <= 0.0001). Soil nitrate, the carbon to nitrogen
      ratio, and microbial biomass nitrogen were the most significant predictors of
      denitrification potential. Denitrification potential, potential net nitrogen
      nitrification and mineralization, and soil nitrate and ammonium, were highest in
      topsoil-amended plots, with increases in denitrification potential of 161.27%
      over control plots. While amendment with topsoil more than doubled several key
      nitrogen cycling processes, more research is required to determine what type and
      level of amendment application are most effective for stimulating removal of
      exogenous nitrate and meeting functional goals within an acceptable time frame. 

PMID- 24915603
TI  - Modification of extracorporeal photopheresis technology with porphyrin
      precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in
      killing human T-cell lymphoma cell lines in vitro.
AB  - BACKGROUND: Extracorporeal photopheresis that exposes isolated white blood cells
      to 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light is used for the
      management of cutaneous T-cell lymphoma and graft-versus-host disease. 8-MOP
      binds to DNA of both tumor and normal cells, thus increasing the risk of
      carcinogenesis of normal cells; and also kills both tumor and normal cells with
      no selectivity after UV-A irradiation. Hexaminolevulinate (HAL)-induced
      protoporphyrin-IX is a potent photosensitizer that localizes at membranous
      structures outside of the nucleus of a cell. HAL-mediated photodynamic therapy
      selectively destroys activated/transformed lymphocytes and induces systemic anti
      tumor immunity. The aim of the present study was to explore the possibility of
      using HAL instead of 8-MOP to kill cells after UV-A exposure. METHODS: Human T
      cell lymphoma Jurkat and Karpas 299 cell lines were used to evaluate cell
      photoinactivation after 8-MOP and/or HAL plus UV-A light with cell proliferation
      and long term survival assays. The mode of cell death was also analyzed by
      fluorescence microscopy. RESULTS: Cell proliferation was decreased by HAL/UV-A, 8
      MOP/UV-A or HAL/8-MOP/UV-A. At sufficient doses, the cells were killed by all the
      regimens; however, the mode of cell death was dependent on the treatment
      conditions. 8-MOP/UV-A produced apoptotic death exclusively; whereas both
      apoptosis and necrosis were induced by HAL/UV-A. CONCLUSION: 8-MOP can be
      replaced by HAL to inactivate the Jurkat and Karpas 299 T-cell lymphoma cells
      after UV-A irradiation via apoptosis and necrosis. This finding may have an
      impact on improved efficacy of photopheresis.

PMID- 24915605
TI  - New insight into the stability of CaCO3 surfaces and nanoparticles via molecular
      simulation.
AB  - Using updated and improved atomistic models for the polymorphs of calcium
      carbonate and their constituent ions in solution, we revisit the question of
      surface energetics and nanoparticle stability. Using a simple lattice-based Monte
      Carlo scheme, we generate nanoparticle configurations in vacuum for all three
      biologically relevant polymorphs of calcium carbonate and establish that the bulk
      energetic ordering of polymorphs persists to the nanoscale. In aqueous
      environments, results based on surface enthalpy alone indicate that formation of
      mineral-water interfaces is marginally favorable in many cases. Including an
      estimate of lost entropy due to formation of structured water layers is
      sufficient to reverse this observation, implying a delicate balance of enthalpy
      and entropy at crystalline CaCO3. In contradiction to some previous studies, we
      find that small calcite nanoparticles with diameters in the range of 1.8-4.1 nm
      do not retain an ordered structure on nanosecond time scales. The consequences of
      these results for simulation studies of biomineralization are discussed. 

PMID- 24915606
TI  - A meta-analysis of acupuncture use in the treatment of cognitive impairment after
      stroke.
AB  - OBJECTIVE: This meta-analysis was conducted to evaluate the efficacy of
      acupuncture on cognitive impairment (function) after a stroke. DESIGN: Randomized
      controlled trials (RCTs) comparing acupuncture with no acupuncture in addition to
      medicine or rehabilitation were identified from databases (PubMed, Cochrane
      Central Register of Controlled Trials, Chinese National Knowledge Infrastructure,
      VIP Chinese Periodical Database, Wangfang Chinese Periodical Database, Chinese
      Bio-medicine Database, Cochrane Library, and Chinese medical literature
      databases) and two relevant journals (Chinese Acupuncture and Moxibustion and the
      Journal of Shanghai Acupuncture and Moxibustion). Meta-analyses were conducted
      for the eligible RCTs. RESULTS: Twenty-one trials with a total of 1421 patients
      met inclusion criteria. Pooled random-effects estimates of the change in the Mini
      Mental State Examination were calculated for the comparison of acupuncture with
      no acupuncture in addition to medicine or rehabilitation. Following 4 weeks and 8
      weeks of intervention with acupuncture, the merged mean difference was 3.14 (95%
      confidence interval [CI], 2.06-4.21; p<.00001) and 2.03 (95% CI, 0.26-3.80;
      p=0.02), respectively. For the comparison of 3-4 weeks of acupuncture with no
      acupuncture in addition to medicine or rehabilitation groups, the merged MD in
      Neurobehavioral Cognitive State Examination total scores was 5.63 (95% CI, 3.95
      7.31; p<.00001). For the comparison of 8-12 weeks of acupuncture with no
      acupuncture in addition to medicine or rehabilitation groups, the P300 latency
      merged MD was -12.80 (95% CI, -21.08 to -4.51; p<.00001), while the P300
      amplitude merged MD was 1.38 (95% CI, 0.93-1.82; p<.00001). Overall, the study
      quality was rated as moderate on the basis of the Cochrane Handbook for
      Systematic Reviews of Interventions (part 2: 8.5). CONCLUSIONS: This meta
      analysis suggests that acupuncture had positive effects on cognitive function
      after stroke and supports the need for additional research on the potential
      benefits of this therapeutic approach.

PMID- 24915607
TI  - Interleukin 17A is an immune marker for chlamydial disease severity and
      pathogenesis in the koala (Phascolarctos cinereus).
AB  - The koala (Phascolarctos cinereus) is an iconic Australian marsupial species that
      is facing many threats to its survival. Chlamydia pecorum infections are a
      significant contributor to this ongoing decline. A major limiting factor in our
      ability to manage and control chlamydial disease in koalas is a limited
      understanding of the koala's cell-mediated immune response to infections by this
      bacterial pathogen. To identify immunological markers associated with chlamydial
      infection and disease in koalas, we used koala-specific Quantitative Real Time
      PCR (qrtPCR) assays to profile the cytokine responses of Peripheral Blood
      Mononuclear Cells (PBMCs) collected from 41 koalas with different stages of
      chlamydial disease. Target cytokines included the principal Th1 (Interferon
      gamma; IFNgamma), Th2 (Interleukin 10; IL10), and pro-inflammatory cytokines
      (Tumor Necrosis Factor alpha; TNFalpha). A novel koala-specific IL17A qrtPCR
      assay was also developed as part of this study to quantitate the gene expression
      of this Th17 cytokine in koalas. A statistically significant higher IL17A gene
      expression was observed in animals with current chlamydial disease compared to
      animals with asymptomatic chlamydial infection. A modest up-regulation of pro
      inflammatory cytokines, such as TNFalpha and IFNgamma, was also observed in these
      animals with signs of current chlamydial disease. IL10 gene expression was not
      evident in the majority of animals from both groups. Future longitudinal studies
      are now required to confirm the role played by cytokines in pathology and/or
      protection against C. pecorum infection in the koala. 

PMID- 24915608
TI  - A DFT study on carbon monoxide adsorption onto hydroxylated alpha-Al2O3(0001)
      surfaces.
AB  - The adsorption of CO onto the hydroxylated alpha-Al2O3(0001) surface was studied
      using density functional theory (DFT). Dissociated adsorption of water was found
      to be stable, with an adsorption energy (Ea) of 1.62 eV at theta(water) = 0.75.
      The most stable hydroxylation form on the clean surface was found to be in the 1
      2 dissociation configuration, where the OH group binds to a surface Al ion and
      the H ion binds to one of the three equivalent surface O ions. The adsorption
      energy of CO was found to be dependent on the degree of pre-hydroxylation of the
      surface as well as on the CO coverage. The highest adsorption energy of CO was
      found when theta(CO) = 0.25 on a pre-hydroxylated surface with theta(water) =
      0.25; Ea = 0.57 eV. The adsorption energy of CO decreased upon increasing the
      degree of pre-hydroxylation. The vibrational frequency of nu(CO) was also
      computed and in all cases it was blue shifted with respect to gas-phase CO. The
      shift, Deltanu, decreased with increasing CO coverage but increased with
      increasing surface hydroxylation. A comparison with available experimental work
      is discussed.

PMID- 24915609
TI  - A comparative study of composition and morphology effect of Ni(x)Co(1-x)(OH)2 on
      oxygen evolution/reduction reaction.
AB  - Oxygen electrochemistry has been intensely studied in the pursuit of sustainable
      and efficient energy conversion and storage solutions. Over the years, developing
      oxygen electrode catalysts with high activity and low cost remains a great
      challenge, despite tremendous efforts. Here, NixCo1-x(OH)2 is used as a
      bifunctional electrocatalyst for both oxygen evolution reaction (OER) and oxygen
      reduction reaction (ORR). The effect of its compositions (x = 1, 0.55, 0) and
      morphologies (including both multilayer and single-layer NixCo1-x(OH)2) on
      catalytic activity is studied systematically in order to optimize the oxygen
      electrochemical performance of 3d-M (M = Ni and Co) metal hydroxides. Our results
      show that the compositions of NixCo1-x(OH)2 has a great influence on
      overpotentials by comparing multilayer Co(OH)2, Ni0.55Co0.45(OH)2, and Ni(OH)2
      for OER. Multilayer Ni(OH)2 exhibits the lowest overpotential of 324 mV at the
      current density of 5 mA/cm(2). Moreover, the overpotential could be greatly
      lowered by using single-layer NixCo1-x(OH)2. Single-layer Ni(OH)2 nanosheet
      manifests 71 mV overpotential decrease (5 mA/cm(2)) and a factor of 14 turnover
      frequency increase as compared to multilayer Co(OH)2 for OER. As for ORR,
      multilayer Co(OH)2 shows the best activity among multilayer NixCo1-x(OH)2.
      Similar to OER, single-layer NixCo1-x(OH)2 demonstrates enhanced ORR activity
      over multilayer NixCo1-x(OH)2. Single-layer Co(OH)2 exhibits the best catalytic
      activity and 3.7 electrons are transferred during oxygen reduction process. The
      successful identification of the composition and morphology effect of 3d metal
      hydroxides on electrocatalytic performance provides the foundation for rational
      design of active sites for high-performance catalyst for both OER and ORR. 

PMID- 24915610
TI  - Conformational insights into the lesion and sequence effects for arylamine
      induced translesion DNA synthesis: 19F NMR, surface plasmon resonance, and primer
      kinetic studies.
AB  - Adduct-induced DNA damage can affect transcription efficiency and DNA replication
      and repair. We previously investigated the effects of the 3'-next flanking base
      (G*CT vs G*CA; G*, FABP, N-(2'-deoxyguanosin-8-yl)-4'-fluoro-4-aminobiphenyl;
      FAF, N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluorene) on the conformation of
      arylamine-DNA lesions in relation to E. coli nucleotide excision repair ( Jain ,
      V. , Hilton , B. , Lin , B. , Patnaik , S. , Liang , F. , Darian , E. , Zou , Y.
      , Mackerell , A. D. , Jr. , and Cho , B. P. ( 2013 ) Nucleic Acids Res. , 41 ,
      869 - 880 ). Here, we report the differential effects of the same pair of
      sequences on DNA replication in vitro by the polymerases exofree Klenow fragment
      (Kf-exo(-)) and Dpo4. We obtained dynamic (19)F NMR spectra for two 19-mer
      modified templates during primer elongation: G*CA [d(5'-CTTACCATCG*CAACCATTC-3')]
      and G*CT [d(5'-CTTACCATCG*CTACCATTC-3')]. We found that lesion stacking is
      favored in the G*CT sequence compared to the G*CA counterpart. Surface plasmon
      resonance binding results showed consistently weaker affinities for the modified
      DNA with the binding strength in the order of FABP > FAF and G*CA > G*CT. Primer
      extension was stalled at (n) and near (n - 1 and n + 1) the lesion site, and the
      extent of blockage and the extension rates across the lesion were influenced by
      not only the DNA sequences but also the nature of the adduct's chemical structure
      (FAF vs FABP) and the polymerase employed (Kf-exo(-) vs Dpo4). Steady-state
      kinetics analysis with Kf-exo(-) revealed the most dramatic sequence and lesion
      effects at the lesion (n) and postinsertion (n + 1) sites, respectively. Taken
      together, these results provide insights into the important role of lesion
      induced conformational heterogeneity in modulating translesion DNA synthesis. 

PMID- 24915611
TI  - Tracking HCC pathogenesis but not the tumor cells after biopsy.

PMID- 24915612
TI  - Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive
      chronic hepatitis B: a randomised open-label trial (OSST trial).
AB  - BACKGROUND & AIMS: Durable post-treatment response is uncommon in chronic
      hepatitis B (CHB) patients on nucleos(t)ide analogue therapy. Response, response
      predictors and safety were assessed in patients who switched from long-term
      entecavir (ETV) to peginterferon alfa-2a. METHODS: Hepatitis B e antigen (HBeAg)
      positive CHB patients who had received ETV for 9-36 months, with HBeAg <100
      PEIU/ml and HBV DNA ?1000 copies/ml, were randomised 1:1 to receive peginterferon
      alfa-2a 180 MUg/week or ETV 0.5mg/day for 48 weeks. The primary endpoint was
      HBeAg seroconversion at week 48 (ClinicalTrials.gov: NCT00940485). RESULTS: 200
      patients were randomised; 197 received ?1 study drug dose. Five patients who were
      anti-HBe-positive at baseline were excluded from the modified intention-to-treat
      population (peginterferon alfa-2a, n = 94; ETV, n = 98). Patients who switched to
      peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs.
      those who continued ETV (14.9% vs. 6.1%; p = 0.0467). Only patients receiving
      peginterferon alfa-2a achieved HBsAg loss (8.5%). Among peginterferon alfa-2a
      treated patients with HBeAg loss and HBsAg <1500 IU/ml at randomisation, 33.3%
      and 22.2% achieved HBeAg seroconversion and HBsAg loss, respectively. Early on
      treatment HBsAg decline predicted response at week 48; highest rates were
      observed in patients with week 12 HBsAg <200 IU/ml (HBeAg seroconversion, 66.7%;
      HBsAg loss, 77.8%). Alanine aminotransferase elevations were not associated with
      viral rebound (n = 38). Peginterferon alfa-2a was well-tolerated. CONCLUSIONS:
      For patients who achieve virological suppression with ETV, switching to a finite
      course of peginterferon alfa-2a significantly increases rates of HBeAg
      seroconversion and HBsAg loss. A response-guided approach may identify patients
      with the greatest chance of success.

PMID- 24915614
TI  - [Alergia Mexico: an Ibero-American journal].

PMID- 24915613
TI  - Waterborne cadmium and nickel impact oxidative stress responses and retinoid
      metabolism in yellow perch.
AB  - In this experiment, we studied the transcriptional and functional (enzymatic)
      responses of yellow perch (Perca flavescens) to metal stress, with a focus on
      oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to
      two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel
      (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly
      increased with increasing metal exposure. The major retinoid metabolites analyzed
      in liver and muscle decreased with metal exposure except at high Cd exposure
      where no variation was reported in liver. A decrease in free plasma
      dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed
      fish, both epidermal retinol dehydrogenase 2 transcription level and
      corresponding enzyme activities retinyl ester hydrolase and lecithin
      dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol
      dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant
      defences, liver transcription levels of catalase, microsomal glutathione-S
      transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd
      exposed fish and this up-regulation was accompanied by an increase in the
      activities of corresponding enzymes, except for microsomal glutathione-S
      transferase. No consistent pattern in antioxidant defence responses was observed
      between molecular and biochemical response when fish were exposed to Ni,
      suggesting a non-synchronous response of antioxidant defence in fish exposed to
      waterborne Ni. There was a general lack of consistency between muscle
      transcription level and enzyme activities analyzed. The overall findings from
      this investigation highlight the usefulness of transcriptional and biochemical
      endpoints in the identification of oxidative stress and vitamin A metabolism
      impairment biomarkers and the potential use of multi-level biological approaches
      when assessing environmental risk in fish. 

PMID- 24915615
TI  - [Estimation of glomerular filtration rate in adults with common variable
      immunodeficiency treated with intravenous immunoglobulin. What formula should we
      use?].
AB  - BACKGROUND: The common variable immunodeficiency (CVID) is characterized by
      absence of isohemagglutinins and two standard deviations of normal levels of
      immunoglobulins. His treatment includes administering immunoglobulin, more
      frequently intravenous (IVIG). A side effect is the possible severe renal
      insufficiency secondary to the use of preparations containing sucrose. These
      patients have weight loss, decreased muscle mass associated with gastrointestinal
      disorders and bronchiectasis that limit physical activity and other factors.
      There are different formulas for determining the glomerular filtration rate, we
      compared the most commonly used to determine the most appropriate in this
      population. OBJECTIVE: To determine the correlation between glomerular filtration
      rate using the MDRD formula, CKD-EPI and Cockcroft-Gault and that obtained
      through the urine creatinine clearance 24 h in patients with common variable
      immunodeficiency who are treated with IVIG. PATIENTS AND METHOD: A transversal,
      observational and descriptive study that included 19 patients with common
      variable immunodeficiency, 12 women and 7 men, mean age 36 years, was done.
      Descriptive statistics with mean, median, mode and standard deviation was used.
      To measure the concordance of the measurements for quantitative variables
      intraclass correlation coefficient was used and to determine the correlation
      between the stages of renal function with different formulas kappa index was
      calculated. RESULTS: The values of the intraclass correlation coefficient showed
      a good correlation between creatinine clearance in 24 h urine with CKDEPI,
      mediocre with MDRD and nil with the Cockroft-Gault formula. CONCLUSIONS:
      Glomerular filtration rate obtained with CKD-EPI proved to be partially most
      useful, with a good correlation in relation to urine creatinine clearance in 24
      h. Its routine use is recommended over other formulas in common variable
      immunodeficiency patients with suspected renal disease secondary to the use of
      IVIG.

PMID- 24915616
TI  - [Study of quality of life in adults with common variable immunodeficiency by
      using the Questionnaire SF-36].
AB  - BACKGROUND: Quality of life is a multidimensional concept that includes physical,
      emotional and social components associated with the disease. The use of tools to
      assess the Quality of Life Health Related (HRQOL) has increased in recent
      decades. Common variable immunodeficiency (CVID) is the most commonly diagnosed
      primary immunodeficiency. OBJECTIVE: To evaluate the quality of life in patients
      with CVID using the questionnaire SF -36. PATIENTS AND METHOD: A descriptive
      cross-sectional survey included 23 patients diagnosed with CVID, belonging to the
      Immunodeficiency Clinic Service of Allergology and Clinical Immunology in CMN
      Siglo XXI, IMSS. The questionnaire SF- 36 validated in Spanish was applied.
      STATISTICAL ANALYSIS: descriptive statistics with simple frequencies and
      percentages, inferential statistics: Fisher exact test and ANOVA to compare
      means. RESULTS: The study involved 23 patients, 14 women (60%) and 9 men (40%),
      mean age 38.6 +/- 14.7 years. The highest score was obtained in 83% emotional
      role. Dimensions with further deterioration in both genders were: 54% general
      health, vitality 59% and physical performance 72%. No differences were found
      regarding gender. The only issue in which statistically significant differences
      were found in patients with more than 3 comorbidities was change in health status
      in the past year (p=0.007). Patients with severe comorbidities, such as
      haematologicaloncological (leukemias, lymphomas, neoplasms), and pulmonary
      (severe bronchiectasis) showed further deterioration in the aspects of physical
      performance 73% and 64% emotional role. 65% of patients reported an improvement
      in health status in 74% in the last year. CONCLUSIONS: Adult patients with CVID
      show deterioration in different dimensions, particularly in the areas of general
      health, vitality and physical performance. Patients with severe comorbidities
      such as leukemia, lymphomas, malignancies and severe bronchiectasis show further
      deterioration in some aspects of quality of life, especially in physical
      performance and emotional role. A higher number of comorbidities was
      significantly associated with a lower score in changing health. The questionnaire
      SF-36 is useful for evaluating the quality of life of our patients with CVID.

PMID- 24915617
TI  - [Frequency of sensitization to mites, cockroach and shrimp in adults with
      respiratory allergy].
AB  - BACKGROUND: Sensitization to mites and cockroach are a common cause of
      respiratory allergy, especially in children. There is little information about
      its cross-reactivity with shrimp, which is common in adult patients. OBJECTIVES:
      To determine the frequency of sensitization to house dust mites (Dermatophagoides
      pteronyssinus, Dermatophagoides farinae) and cockroach species Periplaneta
      americana, in adult patients attending to a third level hospital and to determine
      the frequency of sensitization to shrimp in patients with positive skin test to
      house dust mite and/or cockroach, in patients with clinical manifestations
      suggestive of allergy to shrimp. MATERIAL AND METHOD: A retrospective study was
      done in which results were reviewed of 672 patients clinical records, attending
      to the Allergy and Clinical Immunology department in a third level hospital,
      those patients with positive skin test results to Dermatophagoides and/or
      Periplaneta americana were investigated for sensitization to shrimp through Prick
      to-Prick test. RESULTS: Data from 672 patients were obtained, 69.8% (469) males,
      with a mean age of 33.5 years. Dermatophagoides positivity was 72.2% (486/672),
      and its relationship with other invertebrates that also have tropomyosin was 5.6%
      (4.9% with cockroach and 0.74% with shrimp). CONCLUSIONS: In our population,
      house dust mite sensitization was similar to that reported in the international
      literature. There was low positivity to cockroach, probably due to geographical
      conditions. There is very little information about shrimp's cross-reactivity with
      Dermatophagoides, despite its clinical significance, which requires more specific
      studies such as measurement of specific IgE to tropomyosin.

PMID- 24915618
TI  - [Oral allergy syndrome in adults of a third level hospital].
AB  - BACKGROUND: Oral allergy syndrome (OAS) is the mildest form of an allergic
      reaction to foods. It is characterized by the presence of IgE mediated symptoms
      restricted to oral mucosa after intake of fresh fruits and vegetables. OAS
      diagnosis is based on suggestive clinical manifestations and can be confirmed
      with tests such as prick-to-prick skin test with the food implicated, which have
      a sensitivity > 90%, specificity 30-60%, positive predictive value (PPV) of 40%
      and negative predictive value (NPV) > 95%. OBJECTIVE: To know the prevalence of
      OAS in adult patients attending a third level hospital in southern Mexico City,
      and also describe the demographics of these patients and comorbidities more
      frequently associated. PATIENTS AND METHOD: We studied 44 patients (40 women and
      4 men), with an average age of 33.4 years, with suggestive clinical features of
      OAS, evaluated with prick-by-prick skin tests with fresh food. RESULTS: There was
      a predominance of OAS in woman (91%) and a prevalence of asthma and allergic
      rhinitis of 54% among this population. We found that 60.4% of these patients had
      positive prick-by-prick skin tests, being the most frequently involved families
      of foods: rosaceae (60%), crustaceans (25%), musaceae (23%), actinidacea (21%),
      lauraceae (16%) and cucurbitaceae (16%). Only 5 patients presented adverse
      reactions with prick-by-prick skin tests, in 4 of the cases with grade 3 and
      grade 4 anaphylaxis, while testing with banana-watermelon, peach, papaya and
      peanut, respectively. CONCLUSIONS: Oral allergy syndrome affects more women than
      men, the most frequent comorbidities in patients with oral allergy syndrome are
      allergic rhinitis and asthma, thus, in patients with asthma and allergic
      rhinitis, sensitized to pollens we have to ask about symptoms suggestive of oral
      allergy syndrome.

PMID- 24915619
TI  - [Validation of a diagnostic questionnaire on asthma in children and adults for
      epidemiological studies].
AB  - BACKGROUND: Asthma is a chronic airway inflammatory disease, for identification
      in the population epidemiological studies are required. OBJECTIVE: To validate a
      questionnaire of asthma diagnosis in children and adults. PATIENTS AND METHOD: A
      prolective, cross-sectional, homodemic and multicenter study was done in which a
      questionnaire of asthma for children and adults was subjected to a validation
      process was developed from November 2012 to February 2014, 300 patients, 150
      children and 150 adults of both sexes, obtained from the Allergy department. The
      questionnaire was applied to adults from 13 years of age and to parents who have
      children age 12 and under. Each question was assigned a score as the sum of the
      points according to symptoms, when it reached a score equal to or greater than
      0.75, asthma was diagnosed. RESULTS: The questionnaire of asthma was applied in
      adult population 13-70 years of age and fathers with children was 2-12 years old.
      The tests applied to questionnaire responses showed adults and children in good
      agreement in the test and retest interobserver agreement, this being substantial
      to almost perfect. The tests applied to criterion validity for both
      questionnaires showed a sensitivity of 90% in > 12 y, and 90 % in children, and
      specificity of 91% and 90%, respectively PPV 92% and NPV 90% in > 12 y and 90%
      PPV and 90% NPV in children. The criteria for content validity and expression are
      properly met. The homogeneity test Cronbach's alpha was 0.7. CONCLUSION: The
      questionnaire for diagnosis of asthma in adults and children has good intra- and
      interobserver agreement, with high sensitivity and specificity in the criterion
      validity.

PMID- 24915620
TI  - [Frequency of sensitization to animals in a tropical area].
AB  - BACKGROUND: Pet avoidance is commonly recommended to allergic patients, even if
      an IgE-mediated sensitization has not been demonstrated. This management is
      difficult to accomplish by patients with emotional attachment to their pets and
      the effectiveness is controversial. OBJECTIVE: To assess the sensitization to
      different animals among patients with asthma, rhinitis, conjunctivitis and/or
      dermatitis. To assess the sensitization to different animals among patients with
      asthma, rhinitis, conjunctivitis and/or dermatitis. PATIENTS AND METHOD: A
      retrospective study was performed with 300 previously reported patients with
      asthma, rhinitis, conjunctivitis and/or dermatitis; we organized two groups:
      Group 1 included patients who were tested skin sensitization to both dog and cat.
      Group 2 was comprised of all patients with skin testing droppings or feathers of
      birds (canary, parrot, pigeon or hen). RESULTS: Sensitization to cat and
      especially to dog was high (7% and 47%, respectively). The co-sensitization to
      dog was high among patients sensitized to cat (85%). Sensitization to other
      epithelia (horse, hamster, rabbit, cow) was low. About birds, there was a greater
      sensitization to proteins contained in the feces than in the feathers, pigeon
      sensitization was the most frequent. We observed no differences in the pattern of
      sensitization among patients according to age, gender or allergic symptoms.
      CONCLUSIONS: The frequency of co-sensitization with cat and dog was high, which
      may be explained by shared proteins between the two species as lipocalins. About
      birds, the proteins in pigeon droppings were the main cause of sensitization;
      however, it does not seem to share cross-reactivity with other birds and the
      frequency was relatively low compared with epithelia allergens.

PMID- 24915621
TI  - [Urticaria in children attending allergy services].
AB  - BACKGROUND: There is little information on urticaria occurring in children,
      especially in limited resource countries. OBJECTIVE: To determine the demographic
      and clinical features of urticaria in children living in a developing country.
      PATIENTS AND METHOD: A prospective study was done in children from two allergy
      outpatient clinics were prospectively studied. Clinical data was obtained from
      the medical history and physical examination. Laboratory evaluations and
      immediate-type skin tests with food and aeroallergen extracts were done in
      selected cases. Urticaria subtypes were defined according to current
      EAACI/GA2LEN/WAO guidelines. RESULTS: One hundred and twenty-three subjects were
      studied, 71 with acute urticaria and 52 with chronic urticaria. In patients with
      chronic urticaria, but not in those with acute urticaria, there was a significant
      predominance of girls. Triggers of urticaria were more common in acute than in
      chronic urticaria. Insects, foods, and drugs were the most common inducers of
      symptoms in acute urticaria, while urticaria induced by skin pressure was
      referred more often in chronic urticaria. In patients with acute or chronic
      urticaria there was a higher involvement of the head, upper and lower limbs. In
      patients with chronic urticaria, generalized urticaria, angioedema, and wheals on
      pressure sites were more frequent than in patients with acute urticaria.
      Spontaneous, papular, drug-induced, and dermographic urticaria were the most
      common subtypes in both groups of children. CONCLUSIONS: In children attending
      allergy services, acute urticaria was more frequent than the chronic type.
      Symptom triggers were different in acute than in chronic urticaria. Most common
      subtypes were spontaneous, papular, drug-induced, and dermographic urticaria.

PMID- 24915622
TI  - [Epigenetics, environment and asthma].
AB  - Asthma is a chronic inflammatory disease of the respiratory tract with a complex
      genetic background influenced by the exposition to a series of environmental
      factors. Genetic studies can only elucidate part of the heritability and
      susceptibility of asthma and even though several diseases have an evident genetic
      etiology, only a fraction of the genes involved in their pathogenicity have been
      identified. The epigenetic regulation of the latter is a fact one should bear in
      mind in order to explain the major triggers of diseases whose understanding is
      complicated, such as allergies and asthma. External stimulus such as nourishment,
      stress, physical activity, atmospheric pollution, tobacco smoking and alcohol
      drinking can induce either gene silencing or gene expression. In this regard,
      epigenetics can explain how these environmental factors influence our genetic
      inheritance. There is growing evidence that backs-up the fact that DNA
      methylation, histone post-translational modification and microRNA expression are
      influenced by the environment. This helps explaining how several of the risk
      factors mentioned contribute to the development and inheritance of asthma. In
      this review, different environmental factors and their relation with the main
      epigenetic regulatory mechanisms will be analyzed, as well as their possible role
      in the development of asthma. 

PMID- 24915623
TI  - [Artificial intelligence to assist clinical diagnosis in medicine].
AB  - Medicine is one of the fields of knowledge that would most benefit from a closer
      interaction with Computer studies and Mathematics by optimizing complex,
      imperfect processes such as differential diagnosis; this is the domain of Machine
      Learning, a branch of Artificial Intelligence that builds and studies systems
      capable of learning from a set of training data, in order to optimize
      classification and prediction processes. In Mexico during the last few years,
      progress has been made on the implementation of electronic clinical records, so
      that the National Institutes of Health already have accumulated a wealth of
      stored data. For those data to become knowledge, they need to be processed and
      analyzed through complex statistical methods, as it is already being done in
      other countries, employing: case-based reasoning, artificial neural networks,
      Bayesian classifiers, multivariate logistic regression, or support vector
      machines, among other methodologies; to assist the clinical diagnosis of acute
      appendicitis, breast cancer and chronic liver disease, among a wide array of
      maladies. In this review we shift through concepts, antecedents, current examples
      and methodologies of machine learning-assisted clinical diagnosis.

PMID- 24915625
TI  - Enantioselective Pd-catalyzed allylation of acyclic alpha-fluorinated ketones.
AB  - Significant synthetic challenges remain for the asymmetric synthesis of tertiary
      alpha-fluoro ketones, which are potentially useful molecules for the development
      of drugs, agrochemicals, and functional materials. Herein, we describe the
      development of a method for the catalytic enantioselective synthesis of tertiary
      alpha-fluoro ketones via the Tsuji-Trost reaction of racemic acyclic alpha
      fluorinated ketones. Enantioenriched acyclic alpha-cabonyl tertiary fluorides can
      be produced with the aid of a palladium/phosphinooxazoline catalyst. 

PMID- 24915624
TI  - [Allergic bronchopulmonary aspergillosis].
AB  - Allergic bronchopulmonary aspergillosis is a slowly progressive disease, caused
      by the fungus Aspergillus fumigatus hypersensitivity when it is found in the
      airway. It usually affects asthmatics and patients with cystic fibrosis. We
      report the case of a 20-year-old male patient, student, farmer and rancher with
      chronic respiratory disease. The diagnosis of allergic bronchopulmonary
      aspergillosis was made on the basis of the clinical symptoms and complementary
      studies. 

PMID- 24915626
TI  - Application of multi-omics techniques for bioprocess design and optimization in
      chinese hamster ovary cells.
AB  - Significant improvements in the productivity and quality of therapeutic proteins
      produced in Chinese hamster ovary (CHO) cells have been reported since their
      establishment as host cells for biopharmaceutical production. Initial advances in
      the field focused on engineering strategies to manipulate genes associated with
      proliferation, apoptosis, and various metabolic pathways. Process engineering
      efforts to optimize culture media, batch-feeding strategies and culture
      conditions, including temperature and osmolarity, were also reported. More
      recently, focus has shifted toward enhancing process consistency and product
      quality using systems biology quality by design-based approaches during process
      development. Integration of different data generated using omics technologies,
      such as genomics, transcriptomics, proteomics and metabolomics, has facilitated a
      greater understanding of CHO cell biology. These techniques have enabled the
      provision of global information on dynamic changes in cellular components
      associated with different phenotypes. Using systems biology to understand these
      important host cells at the cellular level will undoubtedly result in further
      progression in the development and expression of biopharmaceutical products in
      CHO cells. 

PMID- 24915627
TI  - Shaping the synthesis and assembly of symmetrically stellated Au/Pd nanocrystals
      with aromatic additives.
AB  - Au/Pd octopods were synthesized with enhanced sample homogeneity through the use
      of aromatic additives. This increase in sample monodispersity facilitates large
      area periodic assembly of stellated metal nanostructures for the first time. The
      aromatic additives were also found to influence the structures of the stellated
      nanocrystals with subtle shape modifications observed that can alter the packing
      arrangement of the Au/Pd octopods. These results indicate the possibility of
      tailored assembly of stellated nanostructures, which would be useful for optical
      applications that require strong and predictable coupling between plasmonic
      building blocks. 

PMID- 24915628
TI  - The cup of youth.

PMID- 24915629
TI  - Intrapartum antibiotics for known maternal Group B streptococcal colonization.
AB  - BACKGROUND: Maternal colonization with group B streptococcus (GBS) during
      pregnancy increases the risk of neonatal infection by vertical transmission.
      Administration of intrapartum antibiotic prophylaxis (IAP) during labor has been
      associated with a reduction in early onset GBS disease (EOGBSD). However,
      treating all colonized women during labor exposes a large number of women and
      infants to possible adverse effects without benefit. OBJECTIVES: To assess the
      effect of intrapartum antibiotics for maternal Group B haemolytic streptococci
      (GBS) colonization on mortality from any cause, from GBS infection and from
      organisms other than GBS. SEARCH METHODS: We updated the search of the Cochrane
      Pregnancy and Childbirth Group's Trials Register on 11 March 2014. SELECTION
      CRITERIA: Randomized trials assessing the impact of maternal IAP on neonatal GBS
      infections were included. DATA COLLECTION AND ANALYSIS: We independently assessed
      eligibility and quality of the studies. MAIN RESULTS: We did not identify any new
      trials from the updated search so the results remain unchanged as follows.We
      included four trials involving 852 women.Three trials (involving 500 women)
      evaluating the effects of IAP versus no treatment were included. The use of IAP
      did not significantly reduce the incidence of all cause mortality, mortality from
      GBS infection or from infections caused by bacteria other than GBS. The incidence
      of early GBS infection was reduced with IAP compared to no treatment (risk ratio
      (RR) 0.17, 95% confidence interval (CI) 0.04 to 0.74, three trials, 488 infants;
      risk difference -0.04, 95% CI -0.07 to -0.01; number needed to treat to benefit
      25, 95% CI 14 to 100, I2 0%). The incidence of LOD or sepsis from organisms other
      than GBS and puerperal infection was not significantly different between
      groups.One trial (involving 352 women) compared intrapartum ampicillin versus
      penicillin and reported no significant difference in neonatal or maternal
      outcomes.We found a high risk of bias for one or more key domains in the study
      methodology and execution. AUTHORS' CONCLUSIONS: Intrapartum antibiotic
      prophylaxis appeared to reduce EOGBSD, but this result may well be due to bias as
      we found a high risk of bias for one or more key domains in the study methodology
      and execution. There is lack of evidence from well designed and conducted trials
      to recommend IAP to reduce neonatal EOGBSD.Ideally the effectiveness of IAP to
      reduce neonatal GBS infections should be studied in adequately sized double-blind
      controlled trials. The opportunity to conduct such trials has likely been lost,
      as practice guidelines (albeit without good evidence) have been introduced in
      many jurisdictions.

PMID- 24915630
TI  - NMDA-glutamatergic activation of the ventral tegmental area induces hippocampal
      theta rhythm in anesthetized rats.
AB  - Glutamate afferents reaching the ventral tegmental area (VTA) affect dopamine
      (DA) cells in this structure probably mainly via NMDA receptors. VTA appears to
      be one of the structures involved in regulation of hippocampal theta rhythm, and
      this work aimed at assessing the role of glutamatergic activation of the VTA in
      the theta regulation. Male Wistar rats (n=17) were divided into groups, each
      receiving intra-VTA microinjection (0.5 MUl) of either solvent (water),
      glutamatergic NMDA agonist (0.2 MUg) or antagonist (MK-801, 3.0 MUg). Changes in
      local field potential were assessed on the basis of peak power (Pmax) and
      corresponding peak frequency (Fmax) for the delta (0.5-3 Hz) and theta (3-6 Hz)
      bands. NMDA microinjection evoked long-lasting hippocampal theta. The rhythm
      appeared with a latency of ca. 12 min post-injection and lasted for over 30 min;
      Pmax in this band was significantly increased for 50 min, while simultaneously
      Pmax in the delta band remained lower than in control conditions. Theta Fmax and
      delta Fmax were increased in almost entire post-injection period (by 0.3-0.5 Hz
      and 0.3-0.7 Hz, respectively). MK-801 depressed the sensory-evoked theta: tail
      pinch could not induce theta for 30 min after the injection; Pmax significantly
      decreased in the theta band and at the same time it increased in the delta band.
      Theta Fmax decreased 10 and 20 min post injection (by 0.4-0.5 Hz) and delta Fmax
      decreased in almost entire post injection period (by 0.3-0.7 Hz). NMDA injection
      generates theta rhythm probably through stimulation of dopaminergic activity
      within the VTA.

PMID- 24915631
TI  - Calibration of BCR-ABL1 mRNA quantification methods using genetic reference
      materials is a valid strategy to report results on the international scale.
AB  - OBJECTIVES: Until recently, diagnostic laboratories that wanted to report on the
      international scale had limited options: they had to align their BCR-ABL1
      quantification methods through a sample exchange with a reference laboratory to
      derive a conversion factor. However, commercial methods calibrated on the World
      Health Organization genetic reference panel are now available. We report results
      from a study designed to assess the comparability of the two alignment
      strategies. DESIGN AND METHODS: Sixty follow-up samples from chronic myeloid
      leukemia patients were included. Two commercial methods calibrated on the genetic
      reference panel were compared to two conversion factor methods routinely used at
      Saint-Louis Hospital, Paris, and at Lille University Hospital. Results were
      matched against concordance criteria (i.e., obtaining at least two of the three
      following landmarks: 50, 75 and 90% of the patient samples within a 2-fold, 3
      fold and 5-fold range, respectively). RESULTS: Out of the 60 samples, more than
      32 were available for comparison. Compared to the conversion factor method, the
      two commercial methods were within a 2-fold, 3-fold and 5-fold range for 53 and
      59%, 89 and 88%, 100 and 97%, respectively of the samples analyzed at Saint
      Louis. At Lille, results were 45 and 85%, 76 and 97%, 100 and 100%, respectively.
      Agreements between methods were observed in the four comparisons performed.
      CONCLUSION: Our data show that the two commercial methods selected are concordant
      with the conversion factor methods. This study brings the proof of principle that
      alignment on the international scale using the genetic reference panel is
      compatible with the patient sample exchange procedure. We believe that these
      results are particularly important for diagnostic laboratories wishing to adopt
      commercial methods.

PMID- 24915632
TI  - The evidence based practice for optimal sample quality for ammonia measurement.
AB  - OBJECTIVES: Pre-analytical factors are a major source of variability in
      laboratory results. Failure to identify these factors can lead to falsely
      increased or decreased results and to erroneous clinical decisions. We aimed to
      investigate several pre-analytical factors influencing ammonia measurement, and
      to quantify their effect on the apparent increase in ammonia concentration.
      DESIGN AND METHODS: Blood samples were taken from 20 healthy volunteers and
      submitted to five different sets of conditions: placing sample on ice vs. room
      temperature immediately after phlebotomy; centrifugation at room temperature vs.
      0 degrees C; measurement at 60 min vs. 30 min after sampling; storing sample at
      room temperature vs. 4 degrees C; and use of stopper (i.e. open vs. closed tube).
      Ammonia was measured in all samples. Additionally, alanine aminotransferase
      (ALT), gamma glutamyltransferase (GGT), free hemoglobin, and complete blood count
      were determined. RESULTS: Samples placed on ice immediately after centrifugation,
      samples spun at 0 degrees C, and samples stored at 4 degrees C all had lower
      changes in ammonia concentration than samples with less favorable treatments
      (P=0.008; P=0.033, and P=0.001, respectively). The observed biases exceeded
      clinically relevant acceptance criteria. Most of the tested parameters were
      significantly associated with increased ammonia. Multiple linear regression
      analysis identified only three variables that contributed significantly to the
      prediction of the dependent variable (i.e. increased NH3): ALT, GGT, and storage.
      CONCLUSION: Pre-analytical factors cause significant errors in ammonia
      measurement. An increase in ammonia concentration is most strongly associated
      with ALT and GGT activity and with storage temperature.

PMID- 24915633
TI  - Football, concussions and biomarkers: ready for more touchdowns?

PMID- 24915634
TI  - Optimizing lead body control during lead extractions: the "Felix helix" lead
      compression method.

PMID- 24915635
TI  - A reproducible Endothelin-1 model of forelimb motor cortex stroke in the mouse.
AB  - BACKGROUND: Despite the availability of numerous transgenic mouse lines to study
      the role of individual genes in promoting neural repair following stroke, few
      studies have availed of this technology, primarily due to the lack of a
      reproducible ischemic injury model in the mouse. Intracortical injections of
      Endothelin-1 (ET1) a potent vasoconstrictive agent, reliably produces focal
      infarcts with concomitant behavioral deficits in rats. In contrast, ET1 infarcts
      in mice are significantly smaller and do not generate consistent behavioral
      deficits. NEW METHOD: We have modified the ET1 ischemia model to target the
      anterior forelimb motor cortex (aFMC) and show that this generates a reproducible
      focal ischemic injury in mice with consistent behavioral deficits. Furthermore,
      we have developed a novel analysis of the cylinder test by quantifying paw
      dragging behavior. RESULTS: ET1 injections which damage deep layer neurons in the
      aFMC generate reproducible deficits on the staircase test. Cylinder test analysis
      showed no forelimb asymmetry post-injection; however, we observed a novel paw
      dragging behavior in mice which is a positive sign of damage to the FMC.
      COMPARISON WITH EXISTING METHODS: Previous ET1 studies have demonstrated
      inconsistent behavioral deficits; however, targeting ET1 injections to the aFMC
      reliably results in staircase deficits. We show that analysis of paw-dragging
      behavior in the cylinder test is a more sensitive measure of damage to the FMC
      than the classical forelimb asymmetry analysis. CONCLUSIONS: We have developed a
      focal ischemic injury model in the mouse that results in reproducible behavioral
      deficits and can be used to test future regenerative therapies.

PMID- 24915636
TI  - Adolescent health and adult labor market outcomes.
AB  - Whereas a large literature has shown the importance of early life health for
      adult socioeconomic outcomes, there is little evidence on the importance of
      adolescent health. We contribute to the literature by studying the impact of
      adolescent health status on adult labor market outcomes using a unique and large
      scale dataset covering almost the entire population of Swedish males. We show
      that most types of major conditions have long-run effects on future outcomes, and
      that the strongest effects result from mental conditions. Including sibling fixed
      effects or twin pair fixed effects reduces the magnitudes of the estimates, but
      they remain substantial. 

PMID- 24915637
TI  - Delivery strategies for sustained drug release in the lungs.
AB  - Drug delivery to the lungs by inhalation offers a targeted drug therapy for
      respiratory diseases. However, the therapeutic efficacy of inhaled drugs is
      limited by their rapid clearance in the lungs. Carriers providing sustained drug
      release in the lungs can improve therapeutic outcomes of inhaled medicines
      because they can retain the drug load within the lungs and progressively release
      the drug locally at therapeutic levels. This review presents the different
      formulation strategies developed to control drug release in the lungs including
      microparticles and the wide array of nanomedicines. Large and porous
      microparticles offer excellent aerodynamic properties. Their large geometric size
      reduces their uptake by alveolar macrophages, making them a suitable carrier for
      sustained drug release in the lungs. Similarly, nanocarriers present significant
      potential for prolonged drug release in the lungs because they largely escape
      uptake by lung-surface macrophages and can remain in the pulmonary tissue for
      weeks. They can be embedded in large and porous microparticles in order to
      facilitate their delivery to the lungs. Conjugation of drugs to polymers as
      polyethylene glycol can be particularly beneficial to sustain the release of
      proteins in the lungs as it allows high protein loading. Drug conjugates can be
      readily delivered to respiratory airways by any current nebulizer device.
      Nonetheless, liposomes represent the formulation most advanced in clinical
      development. Liposomes can be prepared with lipids endogenous to the lungs and
      are particularly safe. Their composition can be adjusted to modulate drug release
      and they can encapsulate both hydrophilic and lipophilic compounds with high drug
      loading. 

PMID- 24915638
TI  - A facile assay to monitor secretory phospholipase A2 using 8-anilino-1
      naphthalenesulfonic acid.
AB  - Secretory phospholipases A2 (sPLA2s) are present in snake venoms, serum, and
      biological fluids of patients with various inflammatory, autoimmune and allergic
      disorders. Lipid mediators in the inflammatory processes have potential value for
      controlling phospholipid metabolism through sPLA2 inhibition. Thus, it demands
      the need for screening of potential leads for sPLA2 inhibition. To date, sPLA2
      activity has been assayed using expensive radioactive or chromogenic substrates,
      thereby limiting a large number of assays. In this study, a simple and sensitive
      NanoDrop assay was developed using non-fluorogenic and non-chromogenic
      phospholipid substrate 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 8
      anilino-1-naphthalenesulfonic acid (ANS) as interfacial hydrophobic probe. The
      modified assay required a 10ng concentration of sPLA2. ANS, as a strong anion,
      binds predominantly to cationic group of choline head of DMPC through ion pair
      formation, imparting hydrophobicity and lipophilicity and resulting in an
      increase in fluorescence. Triton X-100 imparts correct geometrical space during
      sPLA2 catalyzing DMPC, releasing lysophospholipid and acidic myristoyl acid,
      which in turn alters the hydrophobic environment prevailing around ANS-DMPC,
      which leads to weakening of the electrostatic ion pair interaction between DMPC
      and ANS ensuing decrease in fluorescence. These characteristic fluorescence
      changes between DMPC and ANS in response to sPLA2 catalysis are well documented
      and validated in this study. 

PMID- 24915639
TI  - Comparison of weak affinity chromatography and surface plasmon resonance in
      determining affinity of small molecules.
AB  - In this study, we compared affinity data from surface plasmon resonance (SPR) and
      weak affinity chromatography (WAC), two established techniques for determination
      of weak affinity (mM-MUM) small molecule-protein interactions. In the current
      comparison, thrombin was used as target protein. In WAC the affinity constant
      (KD) was determined from retention times, and in SPR it was determined by
      Langmuir isotherm fitting of steady-state responses. Results indicate a strong
      correlation between the two methods (R(2)=0.995, P<0.0001). 

PMID- 24915641
TI  - Metal contaminated biochar and wood ash negatively affect plant growth and soil
      quality after land application.
AB  - Pyrolysis or combustion of waste wood can provide a renewable source of energy
      and produce byproducts which can be recycled back to land. To be sustainable
      requires that these byproducts pose minimal threat to the environment or human
      health. Frequently, reclaimed waste wood is contaminated by preservative-treated
      timber containing high levels of heavy metals. We investigated the effect of
      feedstock contamination from copper-preservative treated wood on the behaviour of
      pyrolysis-derived biochar and combustion-derived ash in plant-soil systems.
      Biochar and wood ash were applied to soil at typical agronomic rates. The
      presence of preservative treated timber in the feedstock increased available soil
      Cu; however, critical Cu guidance limits were only exceeded at high rates of
      feedstock contamination. Negative effects on plant growth and soil quality were
      only seen at high levels of biochar contamination (>50% derived from preservative
      treated wood). Negative effects of wood ash contamination were apparent at lower
      levels of contamination (>10% derived from preservative treated wood). Complete
      removal of preservative treated timber from wood recycling facilities is
      notoriously difficult and low levels of contamination are commonplace. We
      conclude that low levels of contamination from Cu-treated wood should pose
      minimal environmental risk to biochar and ash destined for land application. 

PMID- 24915642
TI  - Roaring function in male goitered gazelles.
AB  - Most of the vocalizations of Antilopinae males are soft and usually only heard
      from a very close distance. The goitered gazelle is a rare exception to this
      rule, and during the rutting period territorial males of this species are among
      the noisiest antelopes. Rutting vocalization is such an essential part of the
      rutting behavior in goitered gazelle that adult males have a hypertrophic larynx,
      the muscle tissues of which increase considerably in size during the rut. We were
      interested in the frequency and variance with which male goitered gazelles emit
      their calls depending on an animal's age, reproductive status and time of the
      year in order to understand the main function of the rutting vocalizations. We
      found that roaring was mostly related to courting displays, while vocalizations
      during aggressive displays were less frequent in male-male interactions. Acoustic
      signals likely enhance courtship displays and also may aid in accelerating female
      ovulation, promoting synchronization of breeding cycles during the mating and
      birthing periods, which last only several days for most of the females in our
      population. We discuss the potential benefits of such behaviors and compare it to
      other species living in similarly extreme environments. 

PMID- 24915640
TI  - Pathogenesis/genetics of frontotemporal dementia and how it relates to ALS.
AB  - One of the most interesting findings in the field of neurodegeneration in recent
      years is tfche discovery of a genetic mutation in the C9orf72 gene, the most
      common mutation found to be causative of sporadic and familial frontotemporal
      lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and concomitant
      FTD-ALS (DeJesus-Hernandez et al., 2011b; Renton et al., 2011). While clinical
      and molecular data, such as the identification of TDP-43 being a common
      pathological protein (Neumann et al., 2006) have hinted at such a link for years,
      the identification of what was formally known as "the chromosome 9 FTLD-ALS gene"
      has provided a foundation for better understanding of the relationship between
      the two. Indeed, it is now recognized that ALS and FTLD-TDP represent a disease
      spectrum. In this review, we will discuss the current genetic and pathological
      features of the FTLD-ALS spectrum. 

PMID- 24915643
TI  - Single and dual task tests of gait speed are equivalent in the prediction of
      falls in older people: a systematic review and meta-analysis.
AB  - Although simple assessments of gait speed have been shown to predict falls as
      well as hospitalisation, functional decline and mortality in older people, dual
      task gait speed paradigms have been increasingly evaluated with respect to fall
      prediction. Some studies have found that dual task walking paradigms can predict
      falls in older people. A systematic review and meta-analysis was conducted to
      determine whether dual task walking paradigms involving a secondary cognitive
      task have greater ability to predict falls than single walking tasks. The meta
      analytic findings indicate single and dual task tests of gait speed are
      equivalent in the prediction of falls in older people and sub-group analyses
      revealed similar findings for studies that included only cognitively impaired
      participants, slow walkers or used secondary mental-tracking or verbal fluency
      tasks. 

PMID- 24915645
TI  - Chronic D-serine reverses arc expression and partially rescues dendritic
      abnormalities in a mouse model of NMDA receptor hypofunction.
AB  - Activity-regulated cytoskeleton-associated protein (Arc) is an immediate early
      gene that is expressed almost exclusively in glutamatergic neurons. Arc protein
      is enriched in the postsynaptic density (PSD) and colocalizes with the N-methyl-D
      aspartate receptor (NMDAR) complex. Arc transcription is positively modulated by
      NMDAR activity and is important for dendritic spine plasticity. Genetic ablation
      of serine racemase (SR-/-), the enzyme that converts L-serine to D-serine, a
      coagonist at the NMDAR, reduces dendritic spine density in the hippocampus. Here
      we demonstrate that SR deficient (SR-/-) mice also have reduced Arc protein
      expression in the hippocampus that can be reversed with chronic D-serine
      administration in adulthood. Furthermore, D-serine treatment partially rescues
      the hippocampal spine deficit in SR-/- mice. These results demonstrate the
      importance of D-serine in regulating the hippocampal expression of Arc in vivo.
      In addition, our findings underscore the potential utility of using the glycine
      modulatory site agonist D-serine to treat disorders that exhibit Arc and
      dendritic spine dysregulation as a consequence of NMDAR hypofunction, such as
      schizophrenia. 

PMID- 24915646
TI  - Motor impairments screened by the movement assessment battery for children-2 are
      related to the visual-perceptual deficits in children with developmental
      coordination disorder.
AB  - This study was to examine to what extent the motor deficits of children with
      Developmental Coordination Disorder (DCD) verified by the Movement Assessment
      Battery for Children-2 (MABC-2) are linked to their visual-perceptual abilities.
      Seventeen children with DCD and seventeen typically developing children (TD) aged
      5-10 years screened from a total of 250 children were recruited. The assessments
      included MABC-2, traditional test of visual perceptual skills (TVPS-R), and
      computerized test for sequential coupling of eye and hand as well as motion
      coherence. The results indicated that children with DCD scored lower than TD in
      MABC-2, and their total scores were highly correlated with manual dexterity
      component scores. DCD group also showed poor visual-perceptual abilities in
      various aspects. The visual discrimination and visual sequential memory from the
      TVPS-R, the sequential coupling of eye and hand, and the motion coherence
      demonstrated a moderate or strong correlation with the MABC-2 in the DCD rather
      than the TD group. It was concluded that the motor problems screened by MABC-2
      were significantly related to the visual-perceptual deficits of children with
      DCD. MABC-2 is suggested to be a prescreening tool to identify the visual
      perceptual related motor deficits.

PMID- 24915644
TI  - Analyzing cell physiology in C. elegans with fluorescent ratiometric reporters.
AB  - Ratiometric fluorescent reporters have recently emerged a new technique to non
      invasively measure aspects of cell physiology such as redox status, calcium
      levels, energy production, and NADH levels. These reporters consist of either a
      single or pair of fluorophores along with specific modifications, such as the
      addition of a protein domain which binds to a metabolite of interest, thereby
      producing gradual alterations in fluorescence in response to changes in the
      measured parameter. Measurement of the changes in fluorescence produces a
      quantitative read-out of the cellular environment. While these reporters were
      initially developed to easily visualize and track changes in cultured cells,
      several groups have adapted these reporters to use in Caenorhabditis elegans
      which opens a new avenue through which to explore cell physiology during
      development or aging, in response to changes in external environment, or in
      response to genetic manipulation. These reporters have the advantage of being
      easily targeted to any part of the worm, and because C. elegans is transparent
      both the reporters and changes in their fluorescence can be clearly observed in
      vivo. Here we discuss the application of ratiometric reporters to C. elegans, and
      outline a method to quantitatively measure changes in intracellular peroxide
      levels using the HyPer ratiometric reporter. However, these principles can be
      applied to alternate ratiometric reporters which are designed to measure either
      other chemical species or other cellular parameters. 

PMID- 24915647
TI  - Training direct care staff to increase positive interactions with individuals
      with developmental disabilities.
AB  - This study tested the effects of direct training on direct care staff's
      initiation of positive interactions with individuals with developmental
      disabilities who resided in an intermediate care facility. Participants included
      four direct care staff and their residents. Direct training included real-time
      prompts delivered via a one-way radio, and data were collected for immediate and
      sustained increases in rates of direct care staff's positive interactions.
      Additionally, this study evaluated the link between increased rates of positive
      interactions and concomitant decreases in residents' challenging behaviors. A
      multiple baseline design across participants was used and results indicated that
      all direct care staff increased their rates of positive interactions during
      direct training. Moreover, all but one participant continued to engage residents
      in positive interactions at levels above the criterion during the maintenance
      phase and follow-up phases. The direct care staff member who did not initially
      meet the criterion improved to adequate levels following one brief performance
      feedback session. With regard to residents' challenging behaviors, across phases,
      residents engaged in low levels of challenging behaviors making those results
      difficult to evaluate. However, improvements in residents' rate of positive
      interactions were noted. 

PMID- 24915648
TI  - Microswitch-aided programs to support physical exercise or adequate ambulation in
      persons with multiple disabilities.
AB  - Three microswitch-aided programs were assessed in three single-case studies to
      enhance physical exercise or ambulation in participants with multiple
      disabilities. Study I was aimed at helping a woman who tended to have the head
      bending forward and the arms down to exercise a combination of appropriate head
      and arms movements. Study II was aimed at promoting ambulation continuity with a
      man who tended to have ambulation breaks. Study III was aimed at promoting
      ambulation with appropriate foot position in a girl who usually showed toe
      walking. The experimental designs of the studies consisted of a multiple probe
      across responses (Study I), an ABAB sequence (Study II), and an ABABB(1) sequence
      (Study III). The last phase of each study was followed by a post-intervention
      check. The microswitches monitored the target responses selected for the
      participants and triggered a computer system to provide preferred stimuli
      contingent on those responses during the intervention phases of the studies. Data
      showed that the programs were effective with each of the participants who learned
      to exercise head and arms movements, increased ambulation continuity, and
      acquired high levels of appropriate foot position during ambulation,
      respectively. The positive performance levels were retained during the post
      intervention checks. The discussion focused on (a) the potential of technology
      aided programs for persons with multiple disabilities and (b) the need of
      replication studies to extend the evidence available in the area. 

PMID- 24915649
TI  - [Medical research on the craniotomy specimens 5000 years ago].
AB  - The skull of the master of M392 tomb 5000 years ago unearthed in Guangrao County,
      Shandong province from 1995 to 1996 had a round and smooth-edged bone defect at
      its left parietal part. By using the methods of morphological observation and
      medical imaging, a contrastive research was made between the characteristics of
      unearthed skull specimens and that of the healing edge of fenestrate bone of the
      skull after craniotomy and that caused by all sorts of diseases. It is thus
      proved that the skull defect of M392 tomb master was caused by craniotomy.

PMID- 24915650
TI  - [The vicissitude of the historically famous medicinal herb Xuan Huanglian (Coptis
      chinensis var. brevisepala)].
AB  - "Xuan Huanglian" is particularly referring to the Coptis chinensis var.
      brevisepala W. T. Wang et Hsiao distributed in the Southern Anhui mountainous
      regions adjacent to Xuan Cheng and its adjoining northwest Zhejiang mountainous
      regions. This herb produced here is of perfect qualities used as an authentic
      medicinal herb from Ben cao jing ji zhu (Variorum of Classic of Materia Medica)
      of 536 A. D to Ben cao gang mu shi yi (Supplement to the Compendium of Materia
      Medica) of 1803 A. D. It was recorded successively as an authentic medicinal herb
      in herbal literature for a period as long as 1200 years. It is declined gradually
      because of prolonged and unlimitedly gathering, leading to the shortage of its
      resources.

PMID- 24915651
TI  - [Factional disputes on the retention or abolition of traditional Chinese medicine
      within the National Government].
AB  - The disputes between Western and traditional Chinese medicine (TCM) started at
      the turn of late Qing Dynasty to early Republican China, intensified in the
      period of construction of National Government at Nanking, lasting for several
      years. The scope of dispute also extended from the initial medical area to the
      mass media, and even to the government interior factions. The form of the combat
      also changed from the debates of original scientific theory to the confrontation
      of political ideology. It was the government interior factional disputes which
      caused "the case of abolition of the traditional Chinese medicine" to abort
      objectively, with the difficult advent of the regulations which saved TCM, to
      certain degree, from vanishing.

PMID- 24915652
TI  - [Brief analysis on the transmission mode of traditional Chinese medicine (TCM) in
      ancient China].
AB  - The transmission route of TCM knowledge in ancient China primarily included
      doctor's transmission and non-doctor's transmission. The doctor's transmission
      mode included lineage-teaching system, elementary study system, transmission
      between schools and the clinical effects on the society etc. Non-doctor's
      transmission mode included literati's interests, literati's sickness, literati's
      health cultivation, the interests of top society, literati's recoding etc.
      Different transmission modes played an important role in the transmission and
      conservation of TCM knowledge as well as a reference to developing the
      transmission of present-day TCM knowledge.

PMID- 24915653
TI  - [The international communication and cooperation of prevention and treatment of
      epidemics in the Republican period of China].
AB  - During the Republican period of China, either the Northern Warlords Government or
      the National Government at Nanking, to different extent, all conducted
      international communication and cooperation in the prevention and treatment of
      epidemics. Firstly, they communicated and cooperated with International League in
      epidemic information, establishment of new health organization, health
      investigation and prevention and treatment of epidemics. Secondly, with WHO in
      epidemic information, live prevention and treatment of epidemics and personnel
      training. In addition, with international medical academic society by the
      initiative means of selecting and sending returned students abroad, dispatching
      overseas staff to study and attend international academic meeting. These
      communications and cooperations not only created good circumstances of
      international society for the prevention and treatment of epidemics in the
      Republican period of China, but also open a special window for the mutual
      understanding between China and the world, at the same time, promoted and
      reinforced independent research and development forces of prevention and
      treatment technology of infectious disease of our nation. Unfortunately, the
      inherent defects of the society of Republic of China greatly detracted from the
      effects of these endeavor.

PMID- 24915654
TI  - [Retrospect of the history of cerebral palsy cognition].
AB  - Throughout the cognition history of cerebral palsy, though these literature and
      art works related to the description of cerebral palsy, yet it only shows that it
      was an "old disease". The real initiative medical study of cerebral palsy started
      at mid 19th century. In the mid to late 19th century, Little, Osler, and Freud,
      the three scholars, perfected the denomination of cerebral palsy, the brain
      derived concept, pathogenic classification, diverse clinical characteristics of
      dyskinesia--oriented manifestations, thus established the basic framework for the
      study of cerebral palsy.

PMID- 24915655
TI  - [Research on Sha zheng quan shu (A complete book for Sha disease) and its main
      circulating editions].
AB  - Sha zheng quan shu (A Complete Book for Sha Disease), the famous books on sha
      diseases in the early Qing dynasty, did exert influence on the classification and
      names of the sha disease ever since. During its circulation, deletions and
      supplementations with frequent changes in its form and contents made its versions
      so diversified and lead to difficulties in both its cataloguing, inheriting and
      searching for its origin and development. By comparing more than dozens of its
      editions, four main groups of version can be recognized, among which Zhang Zhong-
      xin's edition was the earliest one, published four years after Wang Kai's
      original version completed, which could reflect the authentic appearance of
      Wang's original version. Shen Jin-ao re--compiled and modified Zhang's version
      which has several separate editions with substantial changes in its contents,
      book title and author's names, while He Fen revised and reprinted Zhang's
      version, and his version was often misunderstood as the primitive one of Wang's
      version due to its extensive circulation. Hu Jie made a little abridgement based
      on He's version with another book Sha yi lun (Treatise on Pestilent Sha Disease)
      included and attached.

PMID- 24915656
TI  - [Dear colleagues, dear readers,].

PMID- 24915658
TI  - Sentinel event statistics for 2013.

PMID- 24915659
TI  - Clarifying standards applicability to organ procurement organizations.

PMID- 24915657
TI  - Author reply: To PMID 24040771.

PMID- 24915660
TI  - Accepted: New hospital requirements to maintain alignment with CMS.

PMID- 24915662
TI  - Published: Accreditation and certification manual products.

PMID- 24915661
TI  - Implementing a robust equipment maintenance program: CMS and the Joint Commission
      align expectations for alternate maintenance frequencies.

PMID- 24915663
TI  - A systematic approach to basic chest radiograph interpretation: a cardiovascular
      focus.
AB  - In this column, I will provide a general overview to the indications and basic
      chest radiograph features such as density, views and technical quality. A
      systematic approach to radiographic interpretation is outlined. This proposed
      approach follows anatomical structures organized in alphabetical order (airway,
      bone, cardiac, diaphragm, extras and frame), while considering a range of
      pathophysiological findings. Common cardiovascular findings reviewed include
      atelectasis, pneumothorax, pleural effusions, congestive heart failure, pulmonary
      edema, consolidation and pneumonia. While chest radiography is an important
      diagnostic tool for monitoring patients, correlation to the patient's clinical
      assessment is always required.

PMID- 24915664
TI  - Content validity of the Toronto Pain Management Inventory-Acute Coronary Syndrome
      Version.
AB  - BACKGROUND: Cardiac pain and/or discomfort arising from acute coronary syndromes
      (ACS) can often be severe and anxiety-provoking. Cardiac pain, a symptom of
      impaired myocardial perfusion, if left untreated, may lead to further myocardial
      hypoxia, which can potentiate myocardial damage. Evidence suggests that once ACS
      patients are stabilized, their pain may not be adequately assessed. Lack of
      knowledge and problematic beliefs about pain may contribute to this problem. To
      date, no standardized tools are available to examine nurses' specific knowledge
      and beliefs about ACS pain that could inform future educational initiatives. AIM:
      To examine the content validity of the Toronto Pain Management Inventory-ACS
      Version (TPMI-ACS), a 24-item tool designed to assess nurses' knowledge and
      beliefs about ACS pain assessment and management. METHODS: Eight clinical and
      scientific experts rated the relevance of each item using a four-point scale. A
      content validity index was computed for each item (I-CVI), as well as the total
      scale, expressed as the mean item CVI (S-CVI/AVE). Items with an I-CVI > or = 0.7
      were retained, items with an I-CVI ranging from 0.5-0.7 were revised and
      clarified, and items with an I-CVI < or = 0.5 were discarded. RESULTS: I-CVIs
      ranged from 0.5-1.0 and the S-CVI/AVE was 0.90, reflecting high inter-rater
      agreement across items. The least relevant item was eliminated. CONCLUSIONS:
      Preliminary content validity was established on the TPMI-ACS version. All items
      retained in the TPMI-ACS version met requirements for content validity. Further
      evaluation of the psychometric properties of the TPMI-ACS is needed to establish
      criterion and construct validity, as well as reliability indicators.

PMID- 24915665
TI  - "People are starting to value whistleblowers".

PMID- 24915666
TI  - NICE sets out "red flags" on staff.

PMID- 24915667
TI  - "Use international nurses' day to give thanks to the profession".

PMID- 24915668
TI  - "The nursing workforce plays a vital part in clinical research".

PMID- 24915669
TI  - Ethics in research: practice and respect.
AB  - Nursing practice is informed by research, and all nurses, midwives and care staff
      should be research aware even if they do not consider themselves research active.
      The principles of research ethics, based on respect for individuals, should not
      be confined to research. All nurses must be aware of these principles, and
      practise in accordance with them.

PMID- 24915670
TI  - Five dilemmas associated with e-rostering.
AB  - Increased use of e-rostering is likely to benefit nurses and patients, but will
      also create dilemmas for staff. Rosters may not be flexible enough to accommodate
      day-to-day changes, and may also foster unfair treatment and disempower staff.

PMID- 24915671
TI  - National review of asthma deaths: implications.

PMID- 24915672
TI  - Protecting students' supernumerary status.
AB  - Supernumerary status for students is a Nursing and Midwifery Council requirement
      yet there are reports of this being compromised. This paper discusses the value
      of supernumerary status and the need for a collaborative understanding of its
      purpose in protecting students and patients.

PMID- 24915673
TI  - A care bundle approach to falls prevention.
AB  - Falls cause harm and distress to NHS inpatients every year. One hospital's
      implementation of a regional FallSafe project has increased the use of evidence
      based measures to prevent falls. The project relied on a network of falls
      champions, who were nurses or healthcare assistants who taught and inspired their
      colleagues to implement care bundles.

PMID- 24915674
TI  - 60 seconds with Helen Lee.

PMID- 24915675
TI  - Right care for teenagers.

PMID- 24915676
TI  - "The NHS needs more nurses to make it safe".

PMID- 24915677
TI  - Most nurses lack the time to care.

PMID- 24915679
TI  - Nurses need better training in asthma to prevent deaths.

PMID- 24915678
TI  - All students to receive specialist training in dementia nursing.

PMID- 24915680
TI  - "We need to deliver meaningful safety improvements for patients".

PMID- 24915681
TI  - "Motivation made it possible to turn prison healthcare around".

PMID- 24915682
TI  - Using outdoor activities in cardiac recovery.
AB  - Evidence suggests that green spaces next to hospitals can be used to promote
      health. This article reports on a pilot study to determine how hospital green
      spaces can be used for patients with cardiac problems and their rehabilitation
      programmes. Over a six-week period, patients spent one hour per week taking part
      in activities, including tai chi, photography and willow sculpting, as part of
      their rehabilitation programme. Patients showed improved physical health, less
      social isolation, a better overall mood and increased positivity. They were also
      more likely to choose to exercise than at the start of the rehabilitation
      programme, and valued the new skills and knowledge that they gained.

PMID- 24915683
TI  - Barriers to attending cardiac rehabilitation.
AB  - Audits of cardiac rehabilitation in the U.K. have consistently found that the
      goals set out in the National Service Framework for Coronary Heart Disease are
      not being met. This review aimed to identify themes that influence whether
      patients attend cardiac rehabilitation services. This article is the first in a
      two-part series. Part 2 reports the results of a research project looking at
      patients' views of cardiac rehabilitation on the island of Guernsey, and is
      published on page 20.

PMID- 24915684
TI  - Factors in attendance at cardiac rehabilitation.
AB  - AIM: The aim of this study was to advance our understanding of why patients do
      not attend our local cardiac rehabilitation programme. METHOD: All patients
      referred to the CR programme over a three-month period were invited to take part.
      Patients completed three questionnaires. RESULTS: Twenty-five patients agreed to
      take part in the study, 16 of whom returned questionnaires. A preference for
      exercise at home was the most common reason given for not attending phase 3 CR.
      CONCLUSIONS: This study highlighted the need for flexibility in the provision of
      phase-3 CR.

PMID- 24915686
TI  - 60 seconds with Sally Madden.

PMID- 24915685
TI  - Service users' perceptions of student nurses.
AB  - BACKGROUND: A group consisting of a lecturer, staff nurses and mentors to student
      nurses on placement wanted to explore service users' perceptions of student
      nurses. AIM: To explore service users' perceptions of student nurses and their
      experience of being nursed by them. METHOD: This research involved a qualitative
      study of service users' perceptions of student nurses. It involved brief semi
      structured interviews where the service users were asked about their experiences.
      A thematic analysis of their responses was undertaken. RESULTS: In many cases,
      perceptions of student nurses was positive and service users had fond
      recollections but some remembered students in a negative way. Many service users
      remembered student nurses coming and going but considered this to be neither good
      nor bad--they expressed indifference as they were accustomed to having health
      professionals change throughout their care pathway. CONCLUSION: This study
      focused on people with learning disabilities but the findings are likely to apply
      to all care settings, particularly those that are long stay, where the care
      environment becomes home. The findings give student nurses and other staff
      insight into service users' experiences.

PMID- 24915687
TI  - Keeping it clinical.

PMID- 24915688
TI  - High tech = high touch: Innovative technology is making inroads into senior care,
      but a few roadblocks remain.

PMID- 24915689
TI  - Carts confront mobile reality: Nursing staffs are leading an effort to
      incorporate handhelds and even robots into workflows that relied heavily on
      carts.

PMID- 24915690
TI  - HIEs start to pay off: Data exchanges are proving their value, but who will pay
      for them is still an open question.

PMID- 24915691
TI  - A senior moment.

PMID- 24915692
TI  - [XX Conference of law and human genome. Celebrating the twentieth anniversary of
      the Interuniversity Chair in Law and the Human Genome].

PMID- 24915693
TI  - [The construction of the law applicable to human genetics and biotechnology over
      the past two decades].

PMID- 24915694
TI  - [Forty years of biotechnology revolution].

PMID- 24915695
TI  - Perspectives of Medical Law under the challenges of modern biotechnology.

PMID- 24915696
TI  - Science and freedom.

PMID- 24915698
TI  - [Free will and criminal sciences].

PMID- 24915697
TI  - [Freedom versus determinism in criminal law?].

PMID- 24915699
TI  - [The question of human freedom from neuroscience].

PMID- 24915700
TI  - [The identification of individuals through genetic testing and DNA profiling
      banks: policy changes in the European context].

PMID- 24915701
TI  - [The identification of individuals through genetic testing and DNA profiling
      banks].

PMID- 24915702
TI  - [State of affairs and ethical issues in regenerative medicine].

PMID- 24915703
TI  - [Genetic testing and human health].

PMID- 24915704
TI  - [The protection of genetic information].

PMID- 24915705
TI  - [Regenerative medicine and injury crime qualified by the outcome].

PMID- 24915706
TI  - [Compared notes on embryonic stem cell research in Spain and the United Kingdom].

PMID- 24915707
TI  - Nuclear transfer techniques for mitochondrial disorders: how to conceptualise
      them ethically with respect to the germ-line therapies?

PMID- 24915708
TI  - [Notes on bioprospecting and their interactions with humans].

PMID- 24915709
TI  - [Genetic improvement: equality and temporal factor].

PMID- 24915710
TI  - [Ethical and legal implications of interventions for improvement in sports.
      Special consideration of the so-called "gene doping"].

PMID- 24915712
TI  - [Patients, consumers or neither: narratives and positions of women in the case of
      preimplantation diagnosis in Spanish State].

PMID- 24915711
TI  - Synthetic biology and the freedom of scientific research: a fundamental freedom
      in front of a new emerging technology.

PMID- 24915713
TI  - [Genetic data in the face of the international legal order].

PMID- 24915714
TI  - [Genetic testing in the legal capacity to work].

PMID- 24915715
TI  - ["Bad genes" and criminal responsibility].

PMID- 24915716
TI  - [Fundamental rights affected by biological sampling to obtain valid and efficient
      DNA evidence from the point of view of national law and European Union law].

PMID- 24915717
TI  - [Is DNA expert evidence infallible?: approach to the question].

PMID- 24915718
TI  - [Neuroimaging: test to comprehend and understand human actions regarding a
      crime?].

PMID- 24915719
TI  - [Contributions of the National Commission for the Forensic Use of DNA from a
      bioethical perspective].

PMID- 24915720
TI  - [Bioethical and legal aspects in the use of DNA for identification: the case of
      parentage genetic testing].

PMID- 24915721
TI  - [Legal guarantees and ethical implications in the genetic control of immigration
      to Europe].

PMID- 24915722
TI  - [DNA profiling the Spanish criminal process: two decades of technological and
      legislative changes].

PMID- 24915723
TI  - [DNA sampling of the detained individual and the presence of a counsel].

PMID- 24915724
TI  - [The establishment of a bank of DNA profiles in Brazil and its legal-criminal
      implications].

PMID- 24915725
TI  - [The protection of human subjects in the post-genomic era: the intangible human].

PMID- 24915726
TI  - [The human genome and life as argument].

PMID- 24915727
TI  - [Legal and ethical impact of the ENCODE project].

PMID- 24915728
TI  - [Genetic individuality and the Universal Declaration on the Human Genome and
      Human Rights].

PMID- 24915729
TI  - [Consent in research within the Spanish legislation. Reference to Andalusian
      rules].

PMID- 24915730
TI  - [Genome and Law: A reunion twenty years later in Bilbao].

PMID- 24915731
TI  - [The Bilbao Declaration of 1993: the gestation of an innovative proposal].

PMID- 24915732
TI  - [Introducing the Second Declaration of Bilbao].

PMID- 24915733
TI  - 2nd Declaration of Bilbao.

PMID- 24915734
TI  - [A testimony of the XX Conference on Law and the Human Genome].

PMID- 24915735
TI  - Cardiovascular Drug Shortages: Predominant Etiologies, Clinical Implications, and
      Management Strategies.
AB  - OBJECTIVE: To review the literature surrounding the incidence, significance, and
      management of cardiovascular (CV) drug shortages. DATA SOURCES: A literature
      search was conducted using all available indexing databases from January 1996 to
      August 2013, coupled with assessments of the ASHP (American Society of Health
      System Pharmacists) and Food and Drug Administration Web sites designated to drug
      shortages. Data were also gathered through a review of listservs discussing this
      topic. DATA SYNTHESIS: CV drug shortages are among the top 5 national drug class
      shortages that are posing a threat to patient care and public health. When a drug
      shortage occurs, it requires modifications to prescribing and the method
      medications are processed by the pharmacy. These necessary yet cumbersome changes
      can potentially result in less-than-desirable prescribing options and increases
      in personnel time because of administrative and dispensing obstacles. Any one of
      these has the potential to increase costs and/or lead to worse outcomes. Several
      factors have been shown to contribute to these shortages, including manufacturing
      delays, increased demand, medication discontinuations, and lack of raw materials.
      In this article, we review 13 of the critical CV drug shortages, describe their
      role in therapy, discuss the reasons for the shortage, define their impact on
      patient care, and recommend alternative therapies. CONCLUSIONS: CV drug shortages
      are common and can potentially lead to deleterious patient outcomes. Institutions
      should develop plans for early identification, management, and resolution to
      minimize the clinical sequelae associated with drug shortages.

PMID- 24915736
TI  - Nine questions to guide development and implementation of Health in All Policies.
AB  - Based on the policy science literature, we formulate nine core questions that can
      guide the formulation, negotiation, development and implementation of Health in
      All Policies (HiAP). Each question is grounded in the political and policy
      science literature and culminates in checklist items that HiAP developers must
      consider. 

PMID- 24915737
TI  - Parenting Interventions for ADHD: A Systematic Literature Review and Meta
      Analysis.
AB  - OBJECTIVE: To evaluate the evidence base relating to the effectiveness of parent
      administered behavioral interventions for ADHD. METHOD: A systematic review of
      randomized controlled trials or non-randomized but adequately controlled trials
      for children with ADHD or high levels of ADHD symptoms was carried out across
      multiple databases. For meta-analyses, the most proximal ratings of child
      symptoms were used as the primary outcome measure. RESULTS: Eleven studies met
      inclusion criteria (603 children, age range = 33-144 months). Parenting
      interventions were associated with reduction in ADHD symptoms (Standardized Mean
      Difference [SMD] = 0.68; 95% confidence interval [CI] [0.32, 1.04]). There was no
      evidence of attenuation of effectiveness after excluding studies where medication
      was also used. Parenting interventions were also effective for comorbid conduct
      problems (SMD = 0.59; 95% CI [0.29, 0.90]) and parenting self-esteem (SMD = 0.93;
      95% CI [0.48, 1.39]). CONCLUSION: These findings support clinical practice
      guidelines and suggest that parenting interventions are effective. There is a
      need to ensure the availability of parenting interventions in community settings.

PMID- 24915738
TI  - Abnormal origins of the long head of the biceps tendon can lead to rotator cuff
      pathology: a report of two cases.
AB  - Previous case reports have highlighted various anomalous origins of the long head
      of the biceps tendon (LHBT) that do not originate from the superior glenoid
      labrum or supraglenoid tubercle. Yet, these cases were all reported as incidental
      findings and were not thought to cause any significant shoulder pathology. We
      present the magnetic resonance (MR) imaging and clinical treatment of two cases
      where aberrant intra-articular origins of the long head of the biceps tendon from
      the anterior edge of the supraspinatus tendon may have contributed to symptomatic
      rotator cuff pathology. Arthroscopy confirmed MR findings of partial articular
      sided supraspinatus lesions in close proximity to the anomalous origins and
      treatment with tenodesis of the LHBT successfully relieved symptoms. Although
      rare occurrences with subtle and potentially misleading imaging findings, it is
      important to be aware of aberrant origins of the LHBT that may contribute to
      concomitant rotator cuff pathology. 

PMID- 24915739
TI  - Diagnostic criteria of carpal tunnel syndrome using high-resolution
      ultrasonography: correlation with nerve conduction studies.
AB  - The aim of this work was to evaluate the diagnostic performance of grey-scale,
      color Doppler, and dynamic ultrasound (US) for diagnosing carpal tunnel syndrome
      (CTS) using the medical diagnostic test called nerve conduction study (NCS) as
      the reference standard, and to correlate the increase in median nerve (MN) cross
      sectional area (CSA) with severity of CTS. Fifty-one patients (95 wrists) with
      clinical symptoms of idiopathic CTS were recruited. The CSA and flattening ratio
      of the MN were measured at the distal radio-ulnar joint, pisiform, and hamate
      levels; bowing of the flexor retinaculum was determined at the hamate level. The
      hypervascularity of the MN was evaluated. The transverse sliding of the MN was
      observed dynamically and recorded as being either normal or restricted/absent.
      Another 15 healthy volunteers (30 wrists) were recruited as controls.
      Interoperator reliability was established for all criteria. CTS was confirmed in
      75 wrists (75/95: 79%; 14 minimal, 21 mild, 23 moderate, 17 severe). CSA at the
      pisiform level was found to be the most reliable and accurate grey-scale
      criterion to diagnose CTS (optimum threshold: 9.8 mm(2)). There was a good
      correlation between the severity of NCS and CSA (r = 0.78, p < 0.001). The
      sensitivity and specificity of color-Doppler and dynamic US in detecting CTS was
      69, 95, 58, and 86%, respectively. Combination of these subjective criteria with
      CSA increases the sensitivity to 98.3%. US measurement of CSA provides additional
      information about the severity of MN involvement. Color-Doppler and dynamic US
      are useful supporting criteria that may expand the utility of US as a screening
      tool for CTS.

PMID- 24915740
TI  - Bilateral non-osteochondroma-related proximal tibiofibular synostosis.
AB  - We report the case of a 67-year-old male with bilateral proximal tibiofibular
      synostosis, presenting with unilateral symptoms. The patient complained of pain
      around the left fibular head, which was attributed to incomplete bone bridging
      between the proximal tibia and fibula; he underwent proximal fibular head
      resection, which alleviated the pain and improved knee mobility. Eleven months
      later, the patient continued to be pain-free and did not experience any adverse
      effects. An examination of this case and a review of similar cases revealed that
      participation in sport activities such as long-distance running may be one of the
      causes of proximal tibiofibular synostosis. In this report, we have also
      reconsidered the classification of proximal tibiofibular synostosis and provided
      information for a better understanding of this unusual condition. 

PMID- 24915742
TI  - Incarcerated morgagni hernia: an unusual cause of large bowel obstruction.

PMID- 24915743
TI  - Acute spontaneous subdural hematoma in a middle-aged adult: case report and
      review of the literature.
AB  - BACKGROUND: Acute spontaneous subdural hematomas (ASSDH) occur by a variety of
      pathological processes and are less common than trauma-related acute subdural
      hematomas (SDH). Both types are usually seen in the elderly, and only 22 cases of
      ASSDH in patients aged < 40 years have been reported in the medical literature.
      OBJECTIVES: We report a rare case of ASSDH in a middle-aged male with no previous
      history of head trauma. A literature review comparing the clinical presentations,
      etiologies, incidence, mortality rates, and prognostic factors of ASSDH in
      various age groups is discussed. CASE REPORT: A 37-year-old man presented to the
      Emergency Department with headaches, myalgias, and vomiting. Noncontrast computed
      tomography revealed a unilateral ASSDH with 9 mm of midline shift, despite a
      normal neurological examination. Upon admission, the patient developed an
      abducens palsy suggesting increased intracranial pressure and underwent an urgent
      hemicraniectomy. Pathological sampling revealed large atypical cells indicative
      of a hematopoietic neoplasm, but various advanced imaging modalities failed to
      identify signs of cerebral tumor, vascular malformation, or arterial
      extravasation. CONCLUSION: Given the rarity of SDH in nonelderly patients, this
      case suggests a broader differential diagnosis for nontraumatic headaches to
      include arterial and even neoplastic origins. Our literature review confirms the
      paucity of reported incidences of ASSDH, yet reminds medical providers to closely
      monitor for developing neurological symptoms and initiate prompt medical
      intervention when necessary.

PMID- 24915744
TI  - Orbital compressed air and petroleum injury mimicking necrotizing fasciitis.
AB  - BACKGROUND: Orbital injury secondary to petroleum-based products is rare. We
      report the first case, to our knowledge, of a combined compressed air and
      chemical orbital injury, which mimicked necrotizing fasciitis. CASE REPORT: A 58
      year-old man was repairing his motorcycle engine when a piston inadvertently
      fired, discharging compressed air and petroleum-based carburetor cleaner into his
      left eye. He developed surgical emphysema, skin necrosis, and a chemical
      cellulitis, causing an orbital compartment syndrome. He was treated initially
      with antibiotics and subsequently with intravenous steroid and orbital
      decompression surgery. There was almost complete recovery by 4 weeks postsurgery.
      WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Petroleum-based products can
      cause severe skin irritation and necrosis. Compressed air injury can cause
      surgical emphysema. When these two mechanisms of injury are combined, the
      resulting orbitopathy and skin necrosis can mimic necrotizing fasciitis and cause
      diagnostic confusion. A favorable outcome is achievable with aggressive timely
      management.

PMID- 24915746
TI  - Short-course versus long-course chemoradiation in rectal cancer--time to change
      strategies?
AB  - OPINION STATEMENT: There is significant debate regarding the optimal neoadjuvant
      regimen for resectable rectal cancer patients. Short-course radiotherapy, a
      standard approach throughout most of northern Europe, is generally defined as 25
      Gy in 5 fractions over the course of 1 week without the concurrent administration
      of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy
      in 25-28 fractions with the administration of concurrent 5-fluoropyrimidine-based
      chemotherapy and is the standard approach in other parts of Europe and the United
      States. At present, two randomized trials have compared outcomes for short course
      radiotherapy with long-course chemoradiation showing no difference in respective
      study endpoints. Late toxicity data are lacking given limited follow-up. Although
      the ideal neoadjuvant regimen is controversial, our current bias is long-course
      chemoradiation to treat patients with locally advanced, resectable rectal cancer.

PMID- 24915745
TI  - Microsatellite cross-species amplification and utility in southern African
      elasmobranchs: A valuable resource for fisheries management and conservation.
AB  - BACKGROUND: Similarly to the rest of the world, southern Africa's diverse
      chondrichthyan fauna is currently experiencing high fishing pressures from direct
      and non-direct fisheries to satisfy market demands for shark products such as
      fins and meat. In this study, the development of microsatellite markers through
      cross-species amplification of primer sets previously developed for closely
      related species is reported as an alternative approach to de novo marker
      development. This included the design of four microsatellite multiplex assays and
      their cross-species utility in genetic diversity analysis of southern African
      elasmobranchs. As this study forms part of a larger project on the development of
      genetic resources for commercially important and endemic southern African
      species, Mustelus mustelus was used as a candidate species for testing these
      multiplex assays in down-stream applications. RESULTS: Thirty five microsatellite
      primer sets previously developed for five elasmobranch species were selected from
      literature for testing cross-species amplification in 16 elasmobranch species
      occurring in southern Africa. Cross-species amplification success rates ranged
      from 28.6%-71.4%. From the successfully amplified microsatellites, 22 loci were
      selected and evaluated for levels of polymorphism, and four multiplex assays
      comprising of the 22 microsatellites were successfully constructed, optimised and
      characterised in a panel of 87 Mustelus mustelus individuals. A total of 125
      alleles were observed across all loci, with the number of alleles ranging from 3
      12 alleles. Cross-species amplification of the four optimised multiplex assays
      was further tested on 11 commercially important and endemic southern African
      elasmobranch species. Percentage of polymorphism ranged from 31.8%-95.5% in these
      species with polymorphic information content decreasing exponentially with
      evolutionary distance from the source species. CONCLUSIONS: Cross-species
      amplification of the 35 microsatellites proved to be a time- and cost-effective
      approach to marker development in elasmobranchs and enabled the construction of
      four novel multiplex assays for characterising genetic diversity in a number of
      southern African elasmobranch species. This study successfully demonstrated the
      usefulness of these markers in down-stream applications such as genetic diversity
      assessment and species identification which could potentially aid in a more
      integrative, multidisciplinary approach to management and conservation of
      commercially important cosmopolitan and endemic elasmobranch species occurring in
      southern Africa.

PMID- 24915747
TI  - Effects of temperature on leaf hydraulic architecture of tobacco plants.
AB  - MAIN CONCLUSION: Modifications in leaf anatomy of tobacco plants induced greater
      leaf water transport capacity, meeting greater transpirational demands and
      acclimating to warmer temperatures with a higher vapor pressure deficit.
      Temperature is one of the most important environmental factors affecting
      photosynthesis and growth of plants. However, it is not clear how it may alter
      leaf hydraulic architecture. We grew plants of tobacco (Nicotiana tabacum) 'k326'
      in separate glasshouse rooms set to different day/night temperature conditions:
      low (LT 24/18  degrees C), medium (MT 28/22  degrees C), or high (HT 32/26 
      degrees C). After 40 days of such treatment, their leaf anatomies, leaf
      hydraulics, photosynthetic rates, and instantaneous water-use efficiency (WUEi)
      were measured. Compared with those under LT, plants exposed to HT or MT
      conditions had significantly higher values for minor vein density (MVD), stomatal
      density (SD), leaf area, leaf hydraulic conductance (K leaf), and light-saturated
      photosynthetic rate (A sat), but lower values for leaf water potential (psi l)
      and WUEi. However, those parameters did not differ significantly between HT and
      MT conditions. Correlation analyses demonstrated that SD and K leaf increased in
      parallel with MVD. Moreover, greater SD and K leaf were partially associated with
      accelerated stomatal conductance. And then stomatal conductance was positively
      correlated with A sat. Therefore, under well-watered, fertilized conditions, when
      relative humidity was optimal, changes in leaf anatomy seemed to facilitate the
      hydraulic acclimation to higher temperatures, meeting greater transpirational
      demands and contributing to the maintenance of great photosynthetic rates.
      Because transpiration rate increased more with temperature than photosynthetic
      rate, WUEi reduced under warmer temperatures. Our results indicate that the
      modifications of leaf hydraulic architecture are important anatomical and
      physiological strategies for tobacco plants acclimating to warmer temperatures
      under a higher vapor pressure deficit.

PMID- 24915748
TI  - The kinetic analysis of the substrate specificity of motif 5 in a HAD hydrolase
      type phosphosugar phosphatase of Arabidopsis thaliana.
AB  - The Arabidopsis thaliana gene AtSgpp (locus tag At2g38740), encodes a protein
      whose sequence motifs and expected structure reveal that it belongs to the HAD
      hydrolases subfamily I, with the C1-type cap domain (Caparros-Martin et al. in
      Planta 237:943-954, 2013). In the presence of Mg(2+) ions, the enzyme has a
      phosphatase activity over a wide range of phosphosugar substrates. AtSgpp
      promiscuity is preferentially detectable on D-ribose-5-phosphate, 2-deoxy-D
      ribose-5-phosphate, 2-deoxy-D-glucose-6-phosphate, D-mannose-6-phosphate, D
      fructose-1-phosphate, D-glucose-6-phosphate, DL-glycerol-3-phosphate, and D
      fructose-6-phosphate. Site-directed mutagenesis analysis of the putative
      signature sequence motif-5 (IAGKH), which defines its specific chemistry, brings
      to light the active-site residues Ala-69 and His-72. Mutation A69M, changes the
      pH dependence of AtSgpp catalysis, and mutant protein AtSgpp-H72K was inactive in
      phosphomonoester dephosphorylation. It was also observed that substitutions I68M
      and K71R slightly affect the substrate specificity, while the replacement of the
      entire motif for that of homologous DL-glycerol-3-phosphatase AtGpp (MMGRK) does
      not switch AtSgpp activity to the specific targeting for DL-glycerol-3-phosphate.

PMID- 24915749
TI  - Majority vote and other problems when using computational tools.
AB  - Computational tools are essential for most of our research. To use these tools,
      one needs to know how they work. Problems in application of computational methods
      to variation analysis can appear at several stages and affect, for example, the
      interpretation of results. Such cases are discussed along with suggestions how to
      avoid them. The applications include incomplete reporting of methods, especially
      about the use of prediction tools; method selection on unscientific grounds and
      without consulting independent method performance assessments; extending
      application area of methods outside their intended purpose; use of the same data
      several times for obtaining majority vote; and filtering of datasets so that
      variants of interest are excluded. All these issues can be avoided by
      discontinuing the use software tools as black boxes. 

PMID- 24915750
TI  - Conformational equilibrium and dynamic behavior of bis-N-triflyl substituted 3,8
      diazabicyclo[3.2.1]octane.
AB  - Restricted rotation about the N-S partial double bonds in a bis-N-triflyl
      substituted 3,8-diazabicyclo[3.2.1]octane derivative 1 has been frozen at low
      temperature (DeltaG(?)  = 11.6 kcal mol(-1)), and the existence of all four
      rotamers about the two N-S bonds, 3-in,8-in, 3-in,8-out, 3-out,8-in, and 3-out,8
      out, respectively, proved experimentally by NMR spectroscopy and theoretically by
      DFT and MP2 calculations.

PMID- 24915751
TI  - Micropatterned single-walled carbon nanotube electrodes for use in high
      performance transistors and inverters.
AB  - We demonstrated the solution-processed single-walled carbon nanotube (SWNT)
      source-drain electrodes patterned using a plasma-enhanced detachment patterning
      method for high-performance organic transistors and inverters. The high
      resolution SWNT electrode patterning began with the formation of highly uniform
      SWNT thin films on a hydrophobic silanized substrate. The SWNT source-drain
      patterns were then formed by modulating the interfacial energies of the
      prepatterned elastomeric mold and the SWNT thin film using oxygen plasma. The
      SWNT films were subsequently selectively delaminated using a rubber mold. The
      patterned SWNTs could be used as the source-drain electrodes for both n-type
      PTCDI-C8 and p-type pentacene field-effect transistors (FETs). The n- and p-type
      devices exhibited good and exactly matched electrical performances, with a field
      effect mobility of around 0.15 cm(2) V(-1) s(-1) and an ON/OFF current ratio
      exceeding 10(6). The single electrode material was used for both the n and p
      channels, permitting the successful fabrication of a high-performance
      complementary inverter by connecting a p-type pentacene FET to an n-type PTCDI-C8
      FET. This patterning technique was simple, inexpensive, and easily scaled for the
      preparation of large-area electrode micropatterns for flexible microelectronic
      device fabrication. 

PMID- 24915752
TI  - Safety and efficacy of natalizumab in Belgian multiple sclerosis patients:
      subgroup analysis of the natalizumab observational program.
AB  - Natalizumab (Tysabri((r))) is highly efficacious in controlling disease activity
      in relapsing multiple sclerosis (MS) patients. As it is one of the more recent
      therapies for MS, there remains a need for long-term safety and efficacy data of
      natalizumab in a clinical practice setting. The Tysabri observational program
      (TOP) is an open-label, multicenter, multinational, prospective observational
      study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from
      Europe, Canada and Australia. The objectives of this study are to collect long
      term safety and efficacy data on disease activity and disability progression. We
      report here the interim results of the 563 patients included in TOP between
      December 2007 and 2012 from Belgium. This patient cohort was older at baseline,
      had longer disease duration, higher neurological impairment, and a higher
      baseline annualized relapse rate, when compared to patients included in the
      pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was
      comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p <
      0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The
      cumulative probabilities of sustained disability improvement and progression at
      24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns
      over the follow-up period. Two cases of progressive multifocal
      leukoencephalopathy were diagnosed. Our results are consistent with other
      observational studies in the post-marketing setting.

PMID- 24915753
TI  - Male clients' behaviours with and perspectives about their last male escort
      encounter: comparing repeat versus first-time hires.
AB  - Research on men who have sex with men suggests that condomless anal intercourse
      occurs more frequently in established sexual relationships. While comparable data
      regarding male-for-male escorting is unavailable, research implies that many
      clients seek emotional as well as physical connections with the men they hire. In
      2012, 495 male clients, recruited via daddysreviews.com completed an online
      survey about their last hiring experience. Most participants were from the USA
      (85.7%), the UK and Canada (3.2% each). In total, 75% of encounters involved an
      escort hired for the first time; 25% were with a previously hired escort ('repeat
      encounter'). The client's age, lifetime number of escorts hired and number hired
      in the past year were positively associated with the last encounter being a
      repeat encounter. Cuddling, sharing a meal, drinking alcohol, taking a walk,
      watching a show and shopping were also positively associated with repeat
      encounters. Conversely, none of the sexual behaviours were significantly
      associated with repeat encounters. Repeat encounters were significantly more
      likely to include non-sexual behaviours alongside sexual activities, but no more
      likely to involve condomless anal intercourse. Moreover, clients' knowledge of
      escorts' HIV status was not significantly associated with engaging in condomless
      anal intercourse with repeat encounters. 

PMID- 24915754
TI  - Differences in health behaviours between immigrant and non-immigrant groups: a
      protocol for a systematic review.
AB  - BACKGROUND: Health behaviours are important determinants of health and adoption
      of unhealthy behaviour is considered as one of the mechanisms through which
      immigrants' health changes over time in the host country. The change in health
      behaviours over time can contribute either to improving or worsening the overall
      health status of immigrants. Despite being the important mediators for the change
      in overall health status and chronic health conditions, no previous review
      (either general or systematic) has examined differences in key health behaviours
      simultaneously between immigrants and non-immigrants. This study aims to provide
      a systematic overview of the current global literature on differences in key
      health behaviours (that is, tobacco smoking, physical activity and alcohol
      drinking) between immigrant and non-immigrant groups. METHODS/DESIGN: Empirical
      studies in English language reporting quantitative data simultaneously on both
      immigrant and non-immigrant groups will be considered for this systematic review.
      Electronic scientific searches will be conducted on seven databases to identify
      relevant studies of interests: MEDLINE, CINAHL, PsycINFO, EMBASE, Global Health,
      SocINDEX and ProQuest. In addition, Google/Google Scholar will be used to find
      the relevant studies and personal contact with experts will also be undertaken.
      Titles, abstracts and keywords of studies identified in the search strategies
      will be screened for inclusion criteria. The authors will select the studies
      following the PRISMA guidelines. The quality of included studies will be
      appraised using the Critical Appraisal Skills Programme (CASP) checklists. A
      descriptive summary statistics of included studies will describe the study
      designs, socio-demographic characteristics, and the exposure (immigrant and non
      immigrant groups) and outcome (key health behaviours) measures. P-values and
      confidence intervals (CIs) for the associations between exposure and key health
      behaviours will also be reported. DISCUSSION: This systematic review will
      facilitate a better understanding of differences in key health behaviours between
      immigrant and non-immigrant counterparts. It will provide a rigorous and reliable
      research base for future research and advance information on key health
      behaviours for a range of immigrant groups compared to non-immigrants in the high
      migrant-receiving countries. SYSTEMATIC REVIEW REGISTRATION: This systematic
      review protocol has been registered with PROSPERO (registration number:
      CRD42014008688).

PMID- 24915756
TI  - Population genetic structure of gray wolves (Canis lupus) in a marine archipelago
      suggests island-mainland differentiation consistent with dietary niche.
AB  - BACKGROUND: Emerging evidence suggests that ecological heterogeneity across space
      can influence the genetic structure of populations, including that of long
      distance dispersers such as large carnivores. On the central coast of British
      Columbia, Canada, wolf (Canis lupus L., 1758) dietary niche and parasite
      prevalence data indicate strong ecological divergence between marine-oriented
      wolves inhabiting islands and individuals on the coastal mainland that interact
      primarily with terrestrial prey. Local holders of traditional ecological
      knowledge, who distinguish between mainland and island wolf forms, also informed
      our hypothesis that genetic differentiation might occur between wolves from these
      adjacent environments. RESULTS: We used microsatellite genetic markers to examine
      data obtained from wolf faecal samples. Our results from 116 individuals suggest
      the presence of a genetic cline between mainland and island wolves. This pattern
      occurs despite field observations that individuals easily traverse the 30 km wide
      study area and swim up to 13 km among landmasses in the region. CONCLUSIONS:
      Natal habitat-biased dispersal (i.e., the preference for dispersal into familiar
      ecological environments) might contribute to genetic differentiation.
      Accordingly, this working hypothesis presents an exciting avenue for future
      research where marine resources or other components of ecological heterogeneity
      are present.

PMID- 24915755
TI  - A germline mutation in the BRCA1 3'UTR predicts Stage IV breast cancer.
AB  - BACKGROUND: A germline, variant in the BRCA1 3'UTR (rs8176318) was previously
      shown to predict breast and ovarian cancer risk in women from high-risk families,
      as well as increased risk of triple negative breast cancer. Here, we tested the
      hypothesis that this variant predicts tumor biology, like other 3'UTR mutations
      in cancer. METHODS: The impact of the BRCA1-3'UTR-variant on BRCA1 gene
      expression, and altered response to external stimuli was tested in vitro using a
      luciferase reporter assay. Gene expression was further tested in vivo by
      immunoflourescence staining on breast tumor tissue, comparing triple negative
      patient samples with the variant (TG or TT) or non-variant (GG) BRCA1 3'UTR. To
      determine the significance of the variant on clinically relevant endpoints, a
      comprehensive collection of West-Irish breast cancer patients were tested for the
      variant. Finally, an association of the variant with breast screening clinical
      phenotypes was evaluated using a cohort of women from the High Risk Breast
      Program at the University of Vermont. RESULTS: Luciferase reporters with the
      BRCA1-3'UTR-variant (T allele) displayed significantly lower gene expression, as
      well as altered response to external hormonal stimuli, compared to the non
      variant 3'UTR (G allele) in breast cancer cell lines. This was confirmed
      clinically by the finding of reduced BRCA1 gene expression in triple negative
      samples from patients carrying the homozygous TT variant, compared to non-variant
      patients. The BRCA1-3'UTR-variant (TG or TT) also associated with a modest
      increased risk for developing breast cancer in the West-Irish cohort (OR=1.4, 95%
      CI 1.1-1.8, p=0.033). More importantly, patients with the BRCA1-3'UTR-variant had
      a 4-fold increased risk of presenting with Stage IV disease (p=0.018, OR=3.37,
      95% CI 1.3-11.0). Supporting that this finding is due to tumor biology, and not
      difficulty screening, obese women with the BRCA1-3'UTR-variant had significantly
      less dense breasts (p=0.0398) in the Vermont cohort. CONCLUSION: A variant in the
      3'UTR of BRCA1 is functional, leading to decreased BRCA1 expression, modest
      increased breast cancer risk, and most importantly, presentation with stage IV
      breast cancer, likely due to aggressive tumor biology.

PMID- 24915758
TI  - Please confirm that the regulations on standardised ("plain") packaging of
      cigarettes and tobacco products will be published soon.

PMID- 24915757
TI  - Interstitial 13q14 deletions detected in the karyotype and translocations with
      concomitant deletion at 13q14 in chronic lymphocytic leukemia: different genetic
      mechanisms but equivalent poorer clinical outcome.
AB  - Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic
      lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14
      translocations [t(13q)] with related 13q losses has not been fully elucidated. We
      described clinical and biological characteristics of 25 CLL patients with t(13q),
      and compared with 62 patients carrying interstitial del(13q) by conventional G
      banding cytogenetics (CGC) [i-del(13q)] and 295 patients with del(13q) only
      detected by fluorescence in situ hybridization (FISH) [F-del(13q)]. Besides from
      the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all
      t(13q) cases and a representative group of i-del(13q) and F-del(13q). We analyzed
      NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all,
      25 distinct t(13q) were described. All these cases showed D13S319 deletion while
      32% also lost RB1. The median percentage of 13q-deleted nuclei did not differ
      from i-del(13q) patients (73% vs. 64%), but both were significantly higher than F
      del(13q) (52%, P < 0.001). Moreover, t(13q) patients showed an increased
      incidence of biallelic del(13q) (52% vs. 11.3% and 14.9%, P < 0.001) and higher
      rates of concomitant 17p deletion (37.5% vs. 8.6% and 7.2%, P < 0.001). RB1
      involvement was significantly higher in the i-del(13q) group (79%, P < 0.001).
      Two t(13q) patients (11.8%) carried NOTCH1 mutations. Time to first treatment in
      t(13q) and i-del(13q) was shorter than F-del(13q) (67, 44, and 137 months, P =
      0.029), and preserved significance in the multivariate analysis. In conclusion,
      t(13q) and del(13q) patients detected by CGC constitute a subgroup within the 13q
      deleted CLL patients associated with a worse clinical outcome.

PMID- 24915759
TI  - The 3D transoesophageal echocardiography role in the Impella 3.5 placement.

PMID- 24915760
TI  - Geometrical differences in target volumes based on 18F-fluorodeoxyglucose
      positron emission tomography/computed tomography and four-dimensional computed
      tomography maximum intensity projection images of primary thoracic esophageal
      cancer.
AB  - The objective of the study was to compare geometrical differences of target
      volumes based on four-dimensional computed tomography (4DCT) maximum intensity
      projection (MIP) and 18F-fluorodeoxyglucose positron emission tomography/computed
      tomography (18F-FDG PET/CT) images of primary thoracic esophageal cancer for
      radiation treatment. Twenty-one patients with thoracic esophageal cancer
      sequentially underwent contrast-enhanced three-dimensional computed tomography
      (3DCT), 4DCT, and 18F-FDG PET/CT thoracic simulation scans during normal free
      breathing. The internal gross target volume defined as IGTVMIP was obtained by
      contouring on MIP images. The gross target volumes based on PET/CT images (GTVPET
      ) were determined with nine different standardized uptake value (SUV) thresholds
      and manual contouring: SUV>=2.0, 2.5, 3.0, 3.5 (SUVn); >=20%, 25%, 30%, 35%, 40%
      of the maximum (percentages of SUVmax, SUVn%). The differences in volume ratio
      (VR), conformity index (CI), and degree of inclusion (DI) between IGTVMIP and
      GTVPET were investigated. The mean centroid distance between GTVPET and IGTVMIP
      ranged from 4.98 mm to 6.53 mm. The VR ranged from 0.37 to 1.34, being
      significantly (P<0.05) closest to 1 at SUV2.5 (0.94), SUV20% (1.07), or manual
      contouring (1.10). The mean CI ranged from 0.34 to 0.58, being significantly
      closest to 1 (P<0.05) at SUV2.0 (0.55), SUV2.5 (0.56), SUV20% (0.56), SUV25%
      (0.53), or manual contouring (0.58). The mean DI of GTVPET in IGTVMIP ranged from
      0.61 to 0.91, and the mean DI of IGTVMIP in GTVPET ranged from 0.34 to 0.86. The
      SUV threshold setting of SUV2.5, SUV20% or manual contouring yields the best
      tumor VR and CI with internal-gross target volume contoured on MIP of 4DCT
      dataset, but 3DPET/CT and 4DCT MIP could not replace each other for motion
      encompassing target volume delineation for radiation treatment.

PMID- 24915761
TI  - Advances in bioinformatics: selected papers from APBC 2014.

PMID- 24915762
TI  - Species identification of protected carpet pythons suitable for degraded forensic
      samples.
AB  - In this paper we report on the identification of a section of mitochondrial DNA
      that can be used to identify the species of protected and illegally traded
      pythons of the genus Morelia. Successful enforcement of wildlife laws requires
      forensic tests that can identify the species nominated in the relevant
      legislation. The potentially degraded state of evidentiary samples requires that
      forensic investigation using molecular genetic species identification is
      optimized to interrogate small fragments of DNA. DNA was isolated from 35 samples
      of Morelia spilota from which the complete cytochrome b was sequenced. The ND6
      gene was also sequenced in 32 of these samples. Additional DNA sequences were
      generated from 9 additional species of Morelia. The sequences were aligned by
      Geneious and imported into MEGA to create phylogenetic trees based on the entire
      complex of approximately 1,706 base pairs (bp). To mimic degraded DNA, which is
      usually found in forensic cases, short sub-sections of the full alignment were
      used to generate phylogenetic trees. The sub-sections that had the greatest DNA
      sequence information were in parts of the cytochrome b gene. Our results
      highlight that legislation is presently informed by inadequate taxonomy. We
      demonstrated that a 278 bp region of the cytochrome b gene recovered the topology
      of the phylogenetic tree found with the entire gene sequence and correctly
      identified species of Morelia with a high degree of confidence. The locus
      described in this report will assist in the successful prosecution of alleged
      illegal trade in python species. 

PMID- 24915763
TI  - Propensity matched analysis of longterm outcomes following transcatheter based
      aortic valve implantation versus classic aortic valve replacement in patients
      with previous cardiac surgery.
AB  - BACKGROUND: The aim of this study was to compare outcome of patients with
      previous cardiac surgery undergoing transapical aortic valve implantation (Redo
      TAVI) to those undergoing classic aortic valve replacement (Redo-AVR) by using
      propensity analysis. METHODS: From January 2005 through May 2012, 52 high-risk
      patients underwent Redo-TAVI using a pericardial xenograft fixed within a
      stainless steel, balloon-expandable stent (Edwards SAPIENTM). During the same
      period of time 167 patients underwent classic Redo-AVR. Logistic regression
      analysis was used to identify covariates among 11 baseline patient variables
      including the type of initial surgery. Using the significant regression
      coefficients, each patient's propensity score was calculated, allowing
      selectively matched subgroups of 40 patients each. Initial surgery included
      coronary artery bypass grafting in 30 patients, aortic valve replacement in 7
      patients and mitral valve reconstruction in 3 patients in each group. Follow-up
      was 4 +/- 2 years and was 100% complete. RESULTS: Postoperative chest tube
      drainage (163 +/- 214 vs. 562 +/- 332 ml/24 h, p = 0.02) and incidence of early
      permanent neurologic deficit (0 vs. 13%, p = 0.04) was lower in patients with
      Redo-TAVI and there was a trend towards improved 30-day survival (p = 0.06). Also
      we detected a decreased ventilation time (p = 0.04) and lower transfusion rate of
      allogenic blood products (p <= 0.05) in the Redo-TAVI group. At late follow up
      differences regarding incidence of major adverse events, including death and
      permanent neurologic deficits (25% vs. 43%, p = 0.01) statistically supported
      early postoperative findings. CONCLUSION: The encouraging results regarding early
      and long-term outcomes following TAVI in patients with previous cardiac surgery
      show, that this evolving approach may be particularly beneficial in this patient
      cohort.

PMID- 24915764
TI  - PBHoney: identifying genomic variants via long-read discordance and interrupted
      mapping.
AB  - BACKGROUND: As resequencing projects become more prevalent across a larger number
      of species, accurate variant identification will further elucidate the nature of
      genetic diversity and become increasingly relevant in genomic studies. However,
      the identification of larger genomic variants via DNA sequencing is limited by
      both the incomplete information provided by sequencing reads and the nature of
      the genome itself. Long-read sequencing technologies provide high-resolution
      access to structural variants often inaccessible to shorter reads. RESULTS: We
      present PBHoney, software that considers both intra-read discordance and soft
      clipped tails of long reads (>10,000 bp) to identify structural variants. As a
      proof of concept, we identify four structural variants and two genomic features
      in a strain of Escherichia coli with PBHoney and validate them via de novo
      assembly. PBHoney is available for download at http://sourceforge.net/projects/pb
      jelly/. CONCLUSIONS: Implementing two variant-identification approaches that
      exploit the high mappability of long reads, PBHoney is demonstrated as being
      effective at detecting larger structural variants using whole-genome Pacific
      Biosciences RS II Continuous Long Reads. Furthermore, PBHoney is able to discover
      two genomic features: the existence of Rac-Phage in isolate; evidence of E.
      coli's circular genome.

PMID- 24915765
TI  - The spectroscopic (FT-IR, FT-Raman), MESP, first order hyperpolarizability, NBO
      analysis, HOMO and LUMO analysis of 1,5-dimethyl napthalene by density functional
      method.
AB  - The Fourier-transform infrared and FT-Raman spectra of 1,5-Dimethyl Napthalene
      (15DMN) was recorded in the region 4000-400cm(-1) and 3500-50cm(-1) respectively.
      Quantum chemical calculations of energies, geometrical structure and vibrational
      wavenumbers of 6M2C were carried out by density functional theory (DFT/B3LYP)
      method with 6-311++G(d,p) basis set. The difference between the observed and
      scaled wavenumber values of most of the fundamentals is very small. The values of
      the total dipole moment (MU) and the first order hyperpolarizability (beta) of
      the investigated compound were computed using B3LYP/6-311++G(d,p) calculations.
      The calculated results also show that 15DMN might have microscopic non-linear
      optical, MESP, NBO analysis with non-zero values. A detailed interpretation of
      infrared and Raman spectra of 15DMN is also reported. The calculated HOMO7-LUMO
      energy gap shows that charge transfer occur within the molecule. The molecular
      electrostatic potential map shows that the negative potential sites are on the
      electronegative atoms as well as the positive potential sites are around the
      hydrogen atoms. 

PMID- 24915766
TI  - Theoretical and experimental calculations, Mulliken charges and thermodynamic
      properties of 4-chloro-2-nitroanisole.
AB  - The FT-IR and FT-Raman spectra of 4-chloro-2-nitroanisole were recorded and
      analyzed. The vibrational wavenumbers were examined theoretically with the aid of
      the GAUSSIAN 09 package of programs using the B3LYP/6-311G(d,p) and 6-311++G(d,p)
      levels of theory. The data obtained from vibrational wavenumber calculations are
      used to assign vibrational bands obtained in IR and Raman spectroscopy of the
      studied molecule. The first hyperpolarizability, NBO, HOMO-LUMO, NMR, UV,
      infrared intensities and Raman intensities are reported. The calculated first
      hyperpolarizability is comparable with the reported values of similar derivatives
      and is an attractive object for future studies of non-linear optics. The
      geometrical parameters of the title compound are in good agreement with the
      values of similar structures. 

PMID- 24915767
TI  - Piggyback-acquired hypertrichosis.
AB  - A 9-month-old girl exposed to 5% topical minoxidil for 2 months developed
      generalized hypertrichosis of the exposed and unexposed areas of her body. The
      infant's grandfather had been using minoxidil daily and then propping the baby on
      his shoulders for an hour or more a day. Minoxidil was eliminated from the
      child's environment and 4 months later her hair distribution returned to normal. 

PMID- 24915768
TI  - Retraction.

PMID- 24915771
TI  - C2H2 type of zinc finger transcription factors in foxtail millet define response
      to abiotic stresses.
AB  - C2H2 type of zinc finger transcription factors (TFs) play crucial roles in plant
      stress response and hormone signal transduction. Hence considering its
      importance, genome-wide investigation and characterization of C2H2 zinc finger
      proteins were performed in Arabidopsis, rice and poplar but no such study was
      conducted in foxtail millet which is a C4 Panicoid model crop well known for its
      abiotic stress tolerance. The present study identified 124 C2H2-type zinc finger
      TFs in foxtail millet (SiC2H2) and physically mapped them onto the genome. The
      gene duplication analysis revealed that SiC2H2s primarily expanded in the genome
      through tandem duplication. The phylogenetic tree classified these TFs into five
      groups (I-V). Further, miRNAs targeting SiC2H2 transcripts in foxtail millet were
      identified. Heat map demonstrated differential and tissue-specific expression
      patterns of these SiC2H2 genes. Comparative physical mapping between foxtail
      millet SiC2H2 genes and its orthologs of sorghum, maize and rice revealed the
      evolutionary relationships of C2H2 type of zinc finger TFs. The duplication and
      divergence data provided novel insight into the evolutionary aspects of these TFs
      in foxtail millet and related grass species. Expression profiling of candidate
      SiC2H2 genes in response to salinity, dehydration and cold stress showed
      differential expression pattern of these genes at different time points of
      stresses. 

PMID- 24915772
TI  - An ultralow power athermal silicon modulator.
AB  - Silicon photonics has emerged as the leading candidate for implementing ultralow
      power wavelength-division-multiplexed communication networks in high-performance
      computers, yet current components (lasers, modulators, filters and detectors)
      consume too much power for the high-speed femtojoule-class links that ultimately
      will be required. Here we demonstrate and characterize the first modulator to
      achieve simultaneous high-speed (25 Gb s(-1)), low-voltage (0.5 VPP) and
      efficient 0.9 fJ per bit error-free operation. This low-energy high-speed
      operation is enabled by a record electro-optic response, obtained in a vertical p
      n junction device that at 250 pm V(-1) (30 GHz V(-1)) is up to 10 times larger
      than prior demonstrations. In addition, this record electro-optic response is
      used to compensate for thermal drift over a 7.5  degrees C temperature range with
      little additional energy consumption (0.24 fJ per bit for a total energy
      consumption below 1.03 J per bit). The combined results of highly efficient
      modulation and electro-optic thermal compensation represent a new paradigm in
      modulator development and a major step towards single-digit femtojoule-class
      communications.

PMID- 24915773
TI  - Cardiologist and cardiac surgeon view on decision-making in prosthetic aortic
      valve selection: does profession matter?
AB  - AIMS: Assess and compare among Dutch cardiothoracic surgeons and cardiologists:
      opinion on (1) patient involvement, (2) conveying risk in aortic valve selection,
      and (3) aortic valve preferences. METHODS AND RESULTS: A survey among 117
      cardiothoracic surgeons and cardiologists was conducted. Group responses were
      compared using the Mann-Whitney U test. Most respondents agreed that patients
      should be involved in decision-making, with surgeons leaning more toward patient
      involvement (always: 83 % versus 50 % respectively; p < 0.01) than cardiologists.
      Most respondents found that ideally doctors and patients should decide together,
      with cardiologists leaning more toward taking the lead compared with surgeons (p
      < 0.01). Major risks of the therapeutic options were usually discussed with
      patients, and less common complications to a lesser extent. A wide variation in
      valve preference was noted with cardiologists leaning more toward mechanical
      prostheses, while surgeons more often preferred bioprostheses (p < 0.05).
      CONCLUSION: Patient involvement and conveying risk in aortic valve selection is
      considered important by cardiologists and cardiothoracic surgeons. The medical
      profession influences attitude with regard to aortic valve selection and patient
      involvement, and preference for a valve substitute. The variation in valve
      preference suggests that in most patients both valve types are suitable and
      aortic valve selection may benefit from evidence-based informed shared decision
      making.

PMID- 24915774
TI  - [Not Available].

PMID- 24915775
TI  - [Not Available].

PMID- 24915776
TI  - The complement receptors CD46, CD55 and CD59 are regulated by the tumour
      microenvironment of head and neck cancer to facilitate escape of complement
      attack.
AB  - BACKGROUND: Membrane-bound complement restriction proteins (mCRPs) CD46, CD55 and
      CD59 enable tumour cells to evade complement dependent cytotoxicity and antibody
      dependent killing mechanisms. But less is known about the role of these mCRPs in
      head and neck cancer. METHODS: In this study we determined the expression of the
      mCRPs on head and neck squamous cell carcinoma (HNSCC) cell lines, on tumour
      tissue and TDLNs (tumour-draining lymph nodes) as well as on lymphocytes from
      HNSCC patients. The influence of the HNSCC microenvironment on the mCRP
      regulation was analysed using Flow Cytometry, Western blotting and small
      interfering RNAs (siRNA) transfection studies. RESULTS: We examined the effects
      of the HNSCC tumour milieu on the expression levels of CD46, CD55 and CD59. We
      investigated the susceptibility of HNSCC cells to CDC (complement-dependent
      cytotoxicity) while silencing the mCRPs. Our results demonstrate a huge influence
      of the HNSCC tumour microenvironment on the regulation of mCRP expression and
      show a reciprocal regulation between the different mCRPs themselves. CONCLUSIONS:
      In summary, our data indicate that HNSCC has evolved different strategies to
      evade complement attacks and that the tumour microenvironment leads to the
      enhancement of complement resistance of the surrounding tissue.

PMID- 24915777
TI  - Measurement or estimation of glomerular filtration rate in seminoma patients:
      quite another cup of tea.

PMID- 24915778
TI  - A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK
      inhibitor, in combination with gemcitabine for patients with untreated metastatic
      adenocarcinoma of the pancreas.
AB  - BACKGROUND: Trametinib, an oral mitogen/extracellular signal-related kinase
      (MEK)1/2 inhibitor, holds promise for malignancies with rat sarcoma (RAS)
      mutations, like pancreas cancer. This phase II study was designed to determine
      overall survival (OS) in patients with pancreas cancer treated with trametinib
      and gemcitabine. Secondary end-points included progression-free survival (PFS),
      overall response rate (ORR) and duration of response (DOR); safety end-points
      were also assessed. METHODS: Adults with untreated metastatic adenocarcinoma of
      the pancreas were randomised (1:1) to receive intravenous gemcitabine 1000
      mg/m(2) (weekly * 7 for 8 weeks, then days 1, 8 and 15 of 28-day cycles) plus
      trametinib or placebo 2mg daily. RAS mutations were determined in circulating
      free DNA (cfDNA) and archival tumour tissue. OS was evaluated in kirsten rat
      sarcoma viral oncogene homolog (KRAS) mutant and wild-type subgroups. RESULTS:
      Baseline characteristics for 160 patients were similar in both treatment arms.
      There was no significant difference in OS (hazard ratio (HR) 0.98; 95% confidence
      interval (CI), 0.67-1.44; P=.453); median OS was 8.4 months with gemcitabine plus
      trametinib and 6.7 months with gemcitabine plus placebo. Median PFS (16 versus 15
      weeks), ORR (22% versus 18%) and median DOR (23.9 versus 16.1 weeks) were also
      similar for trametinib and placebo arms, respectively. KRAS mutation-positive
      patients (n=103) showed no difference in OS between arms. Thrombocytopenia,
      diarrhoea, rash and stomatitis were more frequent with trametinib, as was grade 3
      anaemia. CONCLUSIONS: The addition of trametinib to gemcitabine did not improve
      OS, PFS, ORR or DOR in patients with previously untreated metastatic pancreas
      cancer. Outcomes were independent of KRAS mutations determined by cfDNA.

PMID- 24915779
TI  - Intergenerational transmission of corporal punishment in China: the moderating
      role of marital satisfaction and gender.
AB  - The goal of this study was to examine the intergenerational patterns in the
      transmission of parental corporal punishment in China and the moderating effects
      of marital satisfaction (of the second generation: G2) and gender (of three
      generations: G1, G2 and G3) on these patterns. Six hundred thirty-five father
      mother dyads with preschool-aged children were recruited to participate in this
      survey. The results provided evidence of cross-generational continuity in
      parental corporal punishment in Chinese society and also supported the hypothesis
      that same-gender continuity in parental corporal punishment is stronger than
      cross-gender continuity. Moreover, it was found that marital satisfaction
      moderated the transmission of parental corporal punishment, and there were some
      interesting gender differences in the moderator effect. Specifically, marital
      satisfaction buffered the transmission of corporal punishment from grandmothers
      to mothers of daughters and to fathers of sons but strengthened the transmission
      from grandfathers to fathers of sons. The findings broaden our understanding of
      the factors and processes that account for both discontinuity and continuity in
      parental corporal punishment, particularly within the Chinese cultural context. 

PMID- 24915780
TI  - Reply: To PMID 24449403.

PMID- 24915781
TI  - Validation of the Fatigue Severity Scale in chronic hepatitis C.
AB  - BACKGROUND: Fatigue is a common symptom of chronic hepatitis C virus (cHCV)
      infection and a common side effect of interferon-based treatment for cHCV. This
      study provides confirmatory evidence of the reliability and validity of the
      Fatigue Severity Scale (FSS) to document fatigue in cHCV research and identifies
      values that indicate clinically important differences in FSS to aid in
      interpreting fatigue in cHCV clinical trials. METHODS: The study used data from
      two double-blind, randomized, placebo-controlled, Phase IIb trials evaluating the
      efficacy and safety of simeprevir plus peginterferon-alpha/ribavirin in treatment
      naive (PILLAR, n = 386) and treatment-experienced patients (ASPIRE, n = 462) with
      cHCV infection. Patients completed the FSS and EuroQoL 5 dimension questionnaire
      (EQ-5D) at baseline and at regular intervals throughout both trials. Reliability
      was assessed using Cronbach's coefficient alpha at Week 24 (internal consistency
      reliability) and intraclass correlation (ICC) between FSS at Weeks 12 and 24 in
      stable patients (<0.5 g/dL hemoglobin [Hb] change between Weeks 12/24).
      Correlation with the EQ-5D visual analog scale (VAS) and "Usual Activity" domain
      score was used to assess concurrent validity. Clinical validity was evaluated
      using a case-control method to link spontaneously reported fatigue and anemia
      adverse events (AEs) during the study to FSS scores. RESULTS: FSS total scores
      demonstrated good reliability (Cronbach's alpha: 0.95, 0.96; ICC: 0.74, 0.86 for
      PILLAR and ASPIRE, respectively) and concurrent validity (correlation with EQ-5D
      VAS: -0.63, -0.66) with a monotonic relationship between the EQ-5D "Usual
      Activities" item response and FSS. Clinical validity was confirmed by a
      significant difference between cases and controls for fatigue AEs (p < 0.05);
      however, anemia defined by AE or Hb abnormalities was only weakly related to FSS
      score. Analyses indicate that a change of 0.33-0.82 in mean FSS scores represents
      a meaningful improvement in fatigue, and a one-point change is a conservative
      indicator of an important change in individual FSS scores. CONCLUSION: A
      difference of >=0.7 in mean FSS scores can be considered a clinically important
      difference within groups over time or between groups. A one-point change or less
      in individual FSS scores indicates a clinically relevant change in fatigue.

PMID- 24915782
TI  - Establishing a contextually appropriate laparoscopic program in resource
      restricted environments: experience in Botswana.
AB  - OBJECTIVE: Differences in opinion exist as to the feasibility of establishing
      sustainable laparoscopic programs in resource-restricted environments. At the
      request of local surgeons and the Ministry of Health in Botswana, a training
      program was established to assist local colleagues with laparoscopic surgery. We
      reviewed our multifaceted and evolving international collaboration and
      highlighted those factors that have helped or hindered this program. METHODS:
      From 2006 to 2012, a training program consisting of didactic teaching,
      telesimulation, Fundamentals of Laparoscopic Surgery certification, yearly
      workshops, and ongoing mentorship was established. We assessed the clinical
      outcomes of patients who underwent laparoscopic cholecystectomy, comparing them
      with patients who underwent open cholecystectomy, and measured the indicators of
      technical independence and program sustainability. RESULTS: Twelve surgeons
      participated in the training program and performed 270 of 288 laparoscopic
      cholecystectomies. Ninety-six open cases were performed by these and 5 additional
      surgeons. Fifteen laparoscopic cases were converted (5.2%). The median
      postoperative length of hospital stay was significantly shorter in the
      laparoscopic group than in the open group (1 day vs 7 days, P < 0.001). As the
      training program progressed, the proportion of laparoscopic cases completed
      without an expatriate surgeon present increased significantly (P = 0.001).
      CONCLUSIONS: A contextually appropriate long-term partnership may assist with
      laparoscopic upskilling of colleagues in low- and middle-income countries. This
      type of collaboration promotes local ownership and may translate into better
      patient outcomes associated with laparoscopic surgery. In resource-restricted
      environments, the factors threatening sustainability may differ from those in
      high-income countries and should be identified and addressed.

PMID- 24915783
TI  - Low-voltage graphene field-effect transistors based on octadecylphosphonic acid
      modified solution-processed high-k dielectrics.
AB  - In this study, a solution-processed bilayer high-k dielectric (Al2O(y)/TiO(x),
      abbrev. as ATO) was used to realize the low-voltage operation of graphene field
      effect transistors (GFETs), in which the graphene was grown by atmospheric
      pressure chemical vapor deposition (APCVD). Upon modifying the interface between
      graphene and the dielectric by octadecylphosphonic acid (ODPA), outstanding room
      temperature hole mobility up to 5805 cm(2) V(-1) s(-1) and electron mobility of
      3232 cm(2) V(-1) s(-1) were obtained in a small gate voltage range from -3.0 V to
      3.0 V under a vacuum. Meanwhile, an excellent on/off current ratio of about 8 was
      achieved. Our studies demonstrate an effective route in which utilizing the low
      temperature solution-processed dielectrics can achieve low-voltage and high
      performance GFETs.

PMID- 24915784
TI  - Encapsulation of porcine pancreatic islets within an immunoprotective capsule
      comprising methacrylated glycol chitosan and alginate.
AB  - Encapsulation of cells in biocompatible polymer matrices represents a powerful
      tool for cell-based therapies and therapeutic delivery systems. This technology
      has successfully been used to deliver pancreatic islets to humans for the
      treatment of Type 1 diabetes. However, the clinical impact of this technology may
      be improved by reducing the inflammatory response brought on after implantation
      of capsules in vivo. Within this study a biocompatible polymeric delivery system
      combining alginate and photo-crosslinked methacrylated glycol chitosan (MGC) was
      developed. This approach involved encapsulating cells in calcium-alginate beads,
      coating with MGC and photo-polymerizing using UVA in the presence of photo
      initiator (VA-086), resulting in the formation of capsules ~600 um in size.
      Crosslinking of the MGC outer wall allowed control over capsule swelling and
      improved the capsules overall properties. Capsule characterization demonstrated
      the stabilizing influence of polymerization and fluorescence imaging showed that
      the distribution of glycol chitosan is dependent on molecular weight. Good islet
      viability and insulin release was demonstrated in vitro over the course of a
      month, and in vivo transplantation of the capsules demonstrated good
      biocompatibility, particularly when compared with standard alginate/poly-l
      ornithine/alginate capsules.

PMID- 24915785
TI  - A simple healthy lifestyle index as a proxy of wellness: a proof of concept.
AB  - The evidence supporting the importance of a healthy lifestyle (active life,
      healthy diet, not smoking, and low stress) as a part of programs for primary and
      secondary prevention of cardiometabolic diseases is strong, compelling, and
      continuously growing. In this study, we test whether a simple web-based healthy
      lifestyle index, using self-reports, is related to indices of cardiovascular
      health and metabolic syndrome and could be employed in large wellness programs
      intended to promote healthy lifestyle. We studied 411 workers in an Italian
      multinational factory who were enrolled in a voluntary program consisting of a
      health checkup and an online questionnaire on lifestyle. These domains were
      combined into a single simple index. Participants were subdivided into three
      healthy lifestyle index (HI) groups (red, yellow, and green) ranging from poor to
      good HI quality (HI from red to green: 41.8 +/- 14.6; 75.7 +/- 8.5; 93.8 +/- 2.2;
      p < 0.05). The groups differed in indicators of cardiovascular and metabolic
      health (waist circumference females: 82.1 +/- 9.56, 78.9 +/- 9.3, 72.7 +/- 6.6;
      males: 95.2 +/- 11.7, 90.0 +/- 9.5, 85.7 +/- 6.1 cm; group difference p < 0.05).
      Moreover, they differed significantly in the likelihood of having more components
      of the metabolic syndrome and, conversely, fewer components of the ideal
      cardiovascular health profile (with red having the worst profile). The red group
      was also characterized by the highest absenteeism. We report for the first time
      that a web-based self-reported poor health behavior was significantly associated
      with clinical and laboratory (partial correlation between HI and high-density
      cholesterol 0.192; body mass index -0.288; systolic blood pressure -0.130; all p
      < 0.05) results indicating a negative cardiometabolic profile.

PMID- 24915786
TI  - Formation of NET, phagocytic activity, surface architecture, apoptosis and
      expression of toll like receptors 2 and 4 (TLR2 and TLR4) in neutrophils of
      mastitic cows.
AB  - Neutrophils employ both oxidative and non oxidative mechanisms to destroy
      pathogens. Function of neutrophils coming in milk during mammary invasion is not
      clearly understood in dairy animals. Therefore, the present study was designed in
      36 Sahiwal cows to see the changes occurring in the neutrophil activity of cows
      suffering from subclinical (SCM) and clinical mastitis (CM). Cows were divided
      into three groups as healthy (n = 12), SCM (n = 12) and CM (n = 12) groups on the
      basis of CMT scoring, gross morphological changes in milk, bacteriological
      examination of milk and by counting milk SCC. Significantly (P < 0.05) higher
      milk SCC, neutrophil percent and significantly (P < 0.05) lower viability of both
      blood and milk neutrophils were observed in CM group of cows as compared to SCM
      and control group of cows. Phagocytic activity (PA) was significantly (P < 0.05)
      higher in milk neutrophils of SCM and CM cows as compared to control cows. Toll
      like receptors 2 and 4 in blood and milk neutrophils were found to be
      significantly (P < 0.05) higher, whereas, apoptosis in terms of altered
      mitochondrial transmembrane potential, Caspase 3 and 7 activities were found to
      be significantly (P < 0.05) lower in CM cows. Alterations in surface architecture
      of neutrophils in terms of formation of pseudopods was observed by scanning
      electron microscope (SEM) and found to be higher in CM cows. Blood neutrophils
      were found to be spherical as compared to milk neutrophils. Formation of
      neutrophil extracellular trap (NETs) were found milk neutrophils of CM cows,
      whereas, SCM and healthy cows did not exhibit NET formation. The study indicated
      a positive correlation between lower neutrophil apoptosis and higher expression
      of TLR2 and TLR4 with the formation of NETs and change in surface architecture.
      Formation of NET like structures seemed to be an effective mode of defense
      employed by neutrophils of cows suffering from clinical mastitis.

PMID- 24915787
TI  - Isolation, cultivation and characterisation of pigeon osteoblasts seeded on
      xenogeneic demineralised cancellous bone scaffold for bone grafting.
AB  - Avian osteoblasts have been isolated particularly from chicken embryo, but data
      about other functional tissue sources of adult avian osteoblast precursors are
      missing. The method of preparation of pigeon osteoblasts is described in this
      study. We demonstrate that pigeon cancellous bone derived osteoblasts have
      particular proliferative capacity in vitro in comparison to mammalian species and
      developed endogenous ALP. Calcium deposits formation in vitro was confirmed by
      alizarin red staining. Only a few studies have attempted to investigate bone
      grafting and treatment of bone loss in birds. Lack of autologous bone grafts in
      birds has prompted investigation into the use of avian xenografts for bone
      augmentation. Here we present a method of xenografting of ostrich demineralised
      cancellous bone scaffold seeded with allogeneic adult pigeon osteoblasts. Ostrich
      demineralised cancellous bone scaffold supported proliferation of pigeon
      osteoblasts during two weeks of co - cultivation in vitro. Scanning electron
      microscopy demonstrated homogeneous adult pigeon osteoblasts attachment and
      distribution on the surface of xenogeneic ostrich demineralised cancellous bone.
      Our preliminary in vitro results indicate that demineralised cancellous bone from
      ostrich tibia could provide an effective biological support for growth and
      proliferation of allogeneic osteoblasts derived from cancellous bone of pigeons. 

PMID- 24915788
TI  - Microarray screening and qRT-PCR evaluation of microRNA markers for forensic body
      fluid identification.
AB  - MicroRNAs (miRNA) are a class of small (~22 nucleotides) noncoding RNAs that
      regulate diverse biological processes at the post-transcriptional level. MiRNAs
      have great potential for forensic body fluid identification because they are
      expressed in a tissue specific manner and are less prone to degradation. Previous
      studies reported several miRNAs as body fluid specific, but there are few
      overlaps among them. Here, we used a genome-wide miRNA microarray containing over
      1700 miRNAs to assay 20 body fluid samples and identify novel miRNAs useful for
      forensic body fluid identification. Based on Shannon Entropy and Q-statistics,
      203 miRNAs specifically expressed in each body fluid were first selected. Eight
      miRNAs were then selected as novel forensically relevant miRNA markers: miR-484
      and miR-182 for blood, miR-223 and miR-145 for saliva, miR-2392 and miR-3197 for
      semen, and miR-1260b and miR-654-5p for vaginal secretions. When the eight
      selected miRNAs were evaluated in 40 additional body fluid samples by qRT-PCR,
      they showed high sensitivity and specificity for the identification of the target
      body fluid. We suggest that the eight miRNAs may be candidates for developing an
      effective molecular assay for forensic body fluid identification. 

PMID- 24915789
TI  - Effect of regional trauma centralization on volume, injury severity and outcomes
      of injured patients admitted to trauma centres.
AB  - BACKGROUND: Centralization of complex healthcare services into specialist high
      volume centres is believed to improve outcomes. For injured patients, few studies
      have evaluated the centralization of major trauma services. The aim of this study
      was to evaluate how a regional trauma network affected trends in admissions, case
      mix, and outcomes of injured patients. METHODS: A retrospective before-after
      study was undertaken of severely injured patients attending four hospitals that
      became major trauma centres (MTCs) in March 2012. Consecutive patients with major
      trauma were identified from a national registry and divided into two groups
      according to injury before or after the launch of a new trauma network. The two
      cohorts were compared for differences in case mix, demand on hospital resources,
      and outcomes. RESULTS: Patient volume increased from 442 to 1326 (200 per cent),
      operations from 349 to 1231 (253 per cent), critical care bed-days from 1100 to
      3704 (237 per cent), and total hospital bed-days from 7910 to 22,772 (188 per
      cent). Patient age increased on MTC designation from 45.0  years before March
      2012 to 48.2 years afterwards (P = 0.021), as did the proportion of penetrating
      injuries (1.8 versus 4.1 per cent; P = 0.025). Injury severity fell as measured
      by median Injury Severity Score (16 versus 14) and Revised Trauma Score (4.1
      versus 7.8). Fewer patients required secondary transfer to a MTC from peripheral
      hospitals (19.9 versus 16.1 per cent; P = 0.100). There were no significant
      differences in total duration of hospital stay, critical care requirements or
      mortality. However, there was a significant increase, from 55.5 to 62.3 per cent
      (P < 0.001), in the proportion of patients coded as having a 'good recovery' at
      discharge after institution of the trauma network. CONCLUSION: MTC designation
      leads to an increased case volume with considerable implications for operating
      theatre capacity and bed occupancy. Although no mortality benefit was
      demonstrated within 6 months of establishing this trauma network, early
      detectable advantages included improved functional outcome at discharge.

PMID- 24915790
TI  - Effect of regional trauma centralization on volume, injury severity and outcomes
      of injured patients admitted to trauma centres (Br J Surg 2014; 101: 959-964).

PMID- 24915791
TI  - Quality of life after surgical resection compared with radiofrequency ablation
      for small hepatocellular carcinomas (Br J Surg 2014; 101: 1006-1015).

PMID- 24915792
TI  - Value of peritoneal cytology in potentially resectable pancreatic cancer (Br J
      Surg 2013; 100: 1791-1796).

PMID- 24915793
TI  - Authors' reply: Value of peritoneal cytology in potentially resectable pancreatic
      cancer (Br J Surg 2013; 100: 1791-1796).

PMID- 24915794
TI  - Author's reply: Lessons learned in breast cancer surgery (Br J Surg 2014; 101:
      145-147).

PMID- 24915795
TI  - Authors' reply: Incisional hernia rate 3 years after midline laparotomy (Br J
      Surg 2014; 101: 51-54).

PMID- 24915796
TI  - Lessons learned in breast cancer surgery (Br J Surg 2014; 101: 145-147).

PMID- 24915797
TI  - Incisional hernia rate 3 years after midline laparotomy (Br J Surg 2014; 101: 51
      54).

PMID- 24915800
TI  - The effects of intra-operative dexmedetomidine on postoperative pain, side
      effects and recovery in colorectal surgery.
AB  - In this double-blind, randomised study, 100 patients undergoing open or
      conventional laparoscopic colorectal surgery received an intra-operative loading
      dose of dexmedetomidine 1 MUg.kg(-1) followed by an infusion of 0.5 MUg.kg(-1)
      .h(-1) , or a bolus and infusion of saline 0.9% of equivalent volume. Forty-six
      patients in the dexmedetomidine group and 50 in the saline group completed the
      study. The area under the curve of numerical rating scores for pain at rest for 1
      48 h postoperatively was significantly lower in the patients receiving
      dexmedetomidine (p = 0.041). There was no difference in morphine consumption,
      duration of recovery ward or hospital stay. From the data obtained in this study,
      we calculated a number needed to treat for effective pain relief of 4. Intra
      operative dexmedetomidine in colorectal surgery resulted in a reduction in
      resting pain scores, but there was no morphine-sparing effect or improvement in
      patients' recovery outcome measures. 

PMID- 24915801
TI  - Basic evaluation of Pentra MS CRP, a new automated hematology analyzer for rapid
      5-part WBC differential and CRP using a small volume of whole blood.
AB  - INTRODUCTION: Pentra MS CRP is a new automated hematology analyzer that can
      rapidly and reliably provide 5-part differential of leukocytes (5-Diff) and C
      reactive protein (CRP) within approximately 3.5 min using a small volume of whole
      blood (35 MUL). METHODS: We evaluated the basic performance of Pentra MS CRP and
      correlations with Sysmex XN-3000, manual microscopic count, and Hitachi
      LABOSPECT. RESULTS: Pentra MS CRP demonstrated good repeatability and linearity
      without any significant carryover for all parameters examined (WBC, RBC, HGB,
      Hct, PLT, 5-Diff, and CRP). Complete blood cell count (CBC) data examined by
      Pentra MS CRP correlated well with those evaluated by Sysmex XN-3000 (R >=
      0.9880). Absolute number of NEU, LYM, and EOS also showed the good correlation (R
      >= 0.9866) between the two analyzers. The correlation with the manual microscopic
      count was within acceptable criteria. Furthermore, when CRP was examined in
      hemolyzed whole blood by Pentra MS CRP and converted to plasma concentrations
      according to Hct, it correlated well (R = 0.9964) with serum CRP examined by
      Hitachi LABOSPECT. CONCLUSION: Pentra MS CRP is a convenient and reliable
      analyzer especially in the emergency unit of hospitals in which the prompt and
      simultaneous measurement of CBC including 5-Diff and CRP is often necessary.

PMID- 24915802
TI  - The oxygen sensor MgFnr controls magnetite biomineralization by regulation of
      denitrification in Magnetospirillum gryphiswaldense.
AB  - BACKGROUND: Magnetotactic bacteria are capable of synthesizing magnetosomes only
      under oxygen-limited conditions. However, the mechanism of the aerobic repression
      on magnetite biomineralization has remained unknown. In Escherichia coli and
      other bacteria, Fnr (fumarate and nitrate reduction regulator) proteins are known
      to be involved in controlling the switch between microaerobic and aerobic
      metabolism. Here, we report on an Fnr-like protein (MgFnr) and its role in growth
      metabolism and magnetite biomineralization in the alphaproteobacterium
      Magnetospirillum gryphiswaldense. RESULTS: Deletion of Mgfnr not only resulted in
      decreased N2 production due to reduced N2O reductase activity, but also impaired
      magnetite biomineralization under microaerobic conditions in the presence of
      nitrate. Overexpression of MgFnr in the WT also caused the synthesis of smaller
      magnetite particles under anaerobic and microaerobic conditions in the presence
      of nitrate. These data suggest that proper expression of MgFnr is required for WT
      like magnetosome synthesis, which is regulated by oxygen. Analyses of
      transcriptional gusA reporter fusions revealed that besides showing similar
      properties to Fnr proteins reported in other bacteria, MgFnr is involved in the
      repression of the expression of denitrification genes nor and nosZ under aerobic
      conditions, possibly owing to several unique amino acid residues specific to MTB
      Fnr. CONCLUSIONS: We have identified and thoroughly characterized the first
      regulatory protein mediating denitrification growth and magnetite
      biomineralization in response to different oxygen conditions in a magnetotactic
      bacterium. Our findings reveal that the global oxygen regulator MgFnr is a
      genuine O2 sensor. It is involved in controlling expression of denitrification
      genes and thereby plays an indirect role in maintaining proper redox conditions
      required for magnetite biomineralization.

PMID- 24915803
TI  - Parental potentiation of vocalization as a marker for filial bonds in infant
      animals.
AB  - Maternal and paternal potentiation of vocalization are two parts of a promising
      model of early life social bonds that has been and can be a useful tool in
      research. Most mammalian infants vocalize when isolated. Interactions with adult
      females just before isolation have been found to increase vocalizations in
      several species. Interactions with littermates and other social stimuli do not.
      In guinea pigs and pigs, the response is specific to the dam. In rats and octagon
      degus, an unrelated adult female from the colony is sufficient. The presence of
      an intact adult male in the test chamber with dam-reared pups evokes behavioral
      inhibition, a fear response. Previous exposure to the male in the home cage,
      biparental rearing, dramatically transforms the response of the pup. The pup
      treats the adult male as it does its dam, including potentiation of vocalization
      during a subsequent isolation. This article outlines the methods, advantages, and
      disadvantages of parental potentiation as a research tool, as well as a brief
      review of the evidence supporting its use as a marker for filial attachment.
      Future research directions are outlined.

PMID- 24915804
TI  - The risk of deep fungal infections during biologic therapy for psoriasis.
AB  - With a growing understanding of the pathogenesis and immunological basis of
      psoriasis, the medical community has seen the development of more focused
      biological treatment options for patients suffering from the disease, which are
      beginning to revolutionize the treatment of psoriasis. It is already well known
      that certain biologics are associated with an increased risk of reactivating
      tuberculosis in patients with latent disease, however, with increasing use of
      biologic agents across indications, there has also been a rise in reports of
      associated deep fungal infections. The mechanism of action of these biologic anti
      psoriatic therapies allows physicians to address the underlying cause of
      patients' symptoms. The question though, is whether this same therapeutic
      mechanism may predispose patients to serious infections, including deep fungal
      infections. 

PMID- 24915806
TI  - The co-construction of medical humanitarianism: analysis of personal,
      organizationally condoned narratives from an agency website.
AB  - Recent years have seen significant growth in both the size and profile of the
      humanitarian sector. However, little research has focused upon the constructions
      of humanitarian practice negotiated by agencies and their workers that serve to
      sustain engagement in the face personal challenges and critique of the
      humanitarian enterprise. This study used the public narrative of 129 website
      postings by humanitarian workers deployed with the health-focused international
      humanitarian organization Medecins Sans Frontieres (MSF) to identify recurrent
      themes in personal, organizationally-condoned, public discourse regarding
      humanitarian practice. Data represented all eligible postings from a feature on
      the agency's UK website from May 2002 to April 2012. The text of postings was
      analysed with respect to emergent themes on an iterative basis. Comprehensive
      coding of material was achieved through a thematic structure that reflected the
      core domains of project details, the working environment, characteristics of
      beneficiaries and recurrent motivational sub-texts. Features of the co
      construction of narratives include language serving to neutralize complex
      political contexts; the specification of barriers as substantive but
      surmountable; the dominance of the construct of national-international in
      understanding the operation of teams; intense personal identification with
      organization values; and the use of resilience as a framing of beneficiary
      adaptation and perseverance in conditions that--from an external perspective-
      warrant despair and withdrawal. Recurrent motivational sub-texts include 'making
      a difference' and contrasts with 'past professional constraints' and 'ordinary
      life back home.' The prominence of these sub-texts not only highlights key
      personal agendas but also suggests--notwithstanding policy initiatives regarding
      stronger contextual rooting and professionalism--continuing organizational
      emphasis on externality and volunteerism. Overall, postings illustrate a complex
      co-construction of medical humanitarianism that reflects a negotiated script of
      personal and organizational understandings adapted to evolving demands of
      humanitarian engagement.

PMID- 24915807
TI  - The health in "life's infinite doings": a response to Andrews et al.

PMID- 24915808
TI  - [To improve the quality of pathologic diagnosis through standardized HER2
      testing].

PMID- 24915805
TI  - Effects of 5,14-HEDGE, a 20-HETE mimetic, on lipopolysaccharide-induced changes
      in MyD88/TAK1/IKKbeta/IkappaB-alpha/NF-kappaB pathway and circulating miR-150,
      miR-223, and miR-297 levels in a rat model of septic shock.
AB  - OBJECTIVES: We have previously demonstrated that a stable synthetic analog of 20
      hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]
      dienoyl)glycine (5,14-HEDGE), which mimics the effects of endogenously produced
      20-HETE, prevents vascular hyporeactivity, hypotension, tachycardia,
      inflammation, and mortality in a rodent model of septic shock. The present study
      was performed to determine whether decreased renal and cardiovascular expression
      and activity of myeloid differentiation factor 88 (MyD88)/transforming growth
      factor-activated kinase 1 (TAK1)/inhibitor of kappaB (IkappaB) kinase beta
      (IKKbeta)/IkappaB-alpha/nuclear factor-kappaB (NF-kappaB) pathway and reduced
      circulating microRNA (miR)-150, miR-223, and miR-297 expression levels
      participate in the protective effect of 5,14-HEDGE against hypotension,
      tachycardia, and inflammation in response to systemic administration of
      lipopolysaccharide (LPS). METHODS: Conscious male Wistar rats received saline (4
      ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured
      using a tail-cuff device. Separate groups of LPS-treated rats were given 5,14
      HEDGE (30 mg/kg) 1 h after injection of saline or LPS. The rats were killed 4 h
      after LPS challenge and blood, kidney, heart, thoracic aorta, and superior
      mesenteric artery were collected for measurement of the protein expression.
      RESULTS: LPS-induced fall in blood pressure and rise in heart rate were
      associated with increased MyD88 expression and phosphorylation of TAK1 and
      IkappaB-alpha in cytosolic fractions of the tissues. LPS also caused an increase
      in both unphosphorylated and phosphorylated NF-kappaB p65 proteins in the
      cytosolic and nuclear fractions as well as nuclear translocation of NF-kappaB
      p65. In addition, serum miR-150, miR-223, and miR-297 expression levels were
      increased in LPS-treated rats. These effects of LPS were prevented by 5,14-HEDGE.
      CONCLUSIONS: These results suggest that downregulation of
      MyD88/TAK1/IKKbeta/IkappaB-alpha/NF-kappaB pathway as well as decreased
      circulating miR-150, miR-223, and miR-297 expression levels participate in the
      protective effect of 5,14-HEDGE against hypotension, tachycardia, and
      inflammation in the rat model of septic shock.

PMID- 24915809
TI  - [New challenges of personalized therapy for breast cancer to pathologists].

PMID- 24915810
TI  - [Emphasis on iatrogenic changes in breast pathology].

PMID- 24915811
TI  - [Assessment of HER2 gene amplification in breast cancer: a comparison of dual
      color in-situ hybridization and fluorescence in-situ hybridization].
AB  - OBJECTIVE: To compare dual-color in-situ hybridization (DISH) with fluorescence
      in situ hybridization(FISH) in evaluating the human HER2 gene status in invasive
      breast cancer. METHODS: HER2 gene status in 110 cases of breast invasive ductal
      carcinomas with a 2+ score on immunohistochemistry (IHC) was investigated by FISH
      and DISH. The 2007 and 2013 ASCO (American Society of Clinical Oncology)/CAP
      (College of American Pathologists) HER2 guideline were used respectively to
      evaluate the agreement between these two techniques. RESULTS: (1) Using the 2007
      ASCO/CAP guideline, the overall concordance between FISH and DISH was 97.3%
      (107/110). Fifty of 51 samples with amplification by FISH were also detected by
      DISH and the remaining one sample was equivocal.Eight of 10 equivocal samples by
      FISH were equivocal by DISH and the remaining two samples were negative. Forty
      nine samples with no amplification by FISH were all negative by DISH. The
      concordance was 98.0%, 8/10 and 100.0% respectively for the FISH positive,
      equivocal and negative groups. (2) Using the 2013 ASCO/CAP guideline, the overall
      concordance between FISH and DISH was 90.0% (99/110). Fifty-three of 55 samples
      with amplification by FISH were also detected by DISH and the remaining two were
      equivocal and negative respectively. Two of 12 equivocal samples by FISH were
      equivocal by DISH and the remaining ten samples were negative in 7 cases and
      equivocal in 3 cases. Forty-three samples with no amplification by FISH were all
      negative by DISH. The concordance was 96.4%, 3/12 and 100.0% respectively for the
      FISH positive, equivocal and negative groups. Pearson correlation analysis
      indicated that the HER2 status detected by FISH and DISH were significantly
      correlated with each other (R=0.584, P<0.01). CONCLUSIONS: There is a high
      concordance between DISH and FISH for assessing the HER2 gene status in invasive
      breast cancer. DISH is a new option for assessing HER2 gene status of breast
      cancer in clinical practice. The clinical significance of the discordance between
      DISH and FISH in equivocal cases warrants further study.

PMID- 24915812
TI  - [Metastases to the breast from non-mammary malignancies: a clinicopathologic
      study of 28 cases].
AB  - OBJECTIVE: To investigate the clinicopathologic characteristics and differential
      diagnosis of the metastases to the breast from non-mammary malignancies. METHODS:
      Twenty-eight cases were collected from 2004 to 2012;microscopic pathologic
      examinations and immunohistochemistry (EnVision method) were performed. RESULTS:
      (1) All except one patients were female, ranging from 16 to 77 years old (average
      45.8 years). Twenty-six (92.9%) patients initially presented with the primary
      site lesions; while the other two (7.1%) patients initially presented with breast
      lesions. The mean interval from primary diagnosis to detection of metastatic
      breast lesions was 32 months (0-228 months). Fifteen patients (53.6%) had other
      metastases detected simultaneously or preceded the breast lesions. (2)
      Macroscopically, all the tumors were relatively circumscribed, with a mean
      diameter of 4.0 cm (0.6-12.0 cm). The histological types of the corresponding
      primary tumors were as follows: eight (28.6%) cases from lung adenocarcinoma,
      five (17.8%) from high-grade ovarian serous carcinoma, three (10.7%) from gastric
      adenocarcinoma, two (7.1%) from rectal adenocarcinoma, one (3.6%) from pancreatic
      neuroendocrine carcinoma, one (3.6%) from prostatic carcinoma, four (14.3%) from
      melanoma, and four (14.3%) from mesenchymal malignant tumors (three
      rhabdomyosarcomas and one epithelioid malignant peripheral nerve sheath tumor,
      MPNST). (3) Histologically, the metastatic tumors showed the morphologic
      characteristics of the primary tumors. Lymph-vascular invasion was observed in 19
      cases. Immunohistochemical features of metastatic tumors were consistent with the
      primary tumors. Molecular markers for breast such as GCDFP15 and mammaglobin were
      negative. Metastatic tumors from lung adenocarcinoma expressed TTF-1 (8/8).
      Ovarian serous carcinoma metastases were positive for PAX8 (5/5) and WT1 (4/5).
      Gastric adenocarcinoma metastases were positive for CDX2 (3/3) and villin (1/3).
      Rectal adenocarcinoma metastases were positive for CDX2 (2/2). Pancreatic
      neuroendocrine tumor metastasis was positive for Syn and CgA (both 1/1). Prostate
      carcinoma metastasis was positive for AR, PSA and P504S (all 1/1). Melanoma
      metastases were positive for HMB45 (2/3) and S-100 protein (3/3).
      Rhabdomyosarcoma metastases were positive for vimentin, desmin and myoD1 (all
      3/3). MPNST metastasis was positive for S-100 protein (1/1). (4) Follow-up data
      was available in 17 patients, with median follow-up time 54 months. The median
      survival from diagnosis to breast metastasis was 24 months.Seven of 17 patients
      died. CONCLUSIONS: Metastases to the breast from non-mammary malignancies are
      rare and show pathologic features of primary tumors. It is usually presumed to be
      a primary breast carcinoma. Histopathologic features and clinical history in
      conjunction with the immunohistochemical results should be considered in
      differentiating a secondary mass from a primary breast carcinoma.

PMID- 24915813
TI  - [Expression of ABCG2 and p-glycoprotein in residual breast cancer tissue after
      chemotherapy and their correlation with epithelial-mesenchymal transition].
AB  - OBJECTIVE: To explore the expression of breast cancer resistance protein (ABCG2),
      p-glycoprotein (P-gp) in residual breast cancer tissue after chemotherapy and
      their correlation with epithelial mesenchymal transition (EMT). METHODS: Seventy
      six cases of breast cancer were collected. The expression of ABCG2, P-gp and EMT
      markers E-cadherin and vimentin in residual breast cancer tissue after
      chemotherapy was detected by immunohistochemistry (EnVision method). MCF7 cells
      were divided into three group:untreated control group, positive control (TGF
      beta1 induced) group and drug surviving cells (DSC) group (selected viable MCF7
      cells after docetaxel and epirubicin treatment). The expression of EMT markers E
      cadherin and vimentin was detected by immunofluorescence. The mRNA and protein
      expression of ABCG2, P-gp and EMT markers were detected by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot, respectively. RESULTS:
      Compared with breast cancer tissue before chemotherapy, ABCG2, P-gp and vimentin
      protein were highly expressed in residual breast cancer tissue after
      chemotherapy. The expression of ABCG2 and P-gp correlated positively with
      vimentin protein (r1=0.97, P1=0.000; r2=0.83, P2=0.001) and negatively with E
      cadherin protein (r3=-0.55, P3=0.010; r4=-0.43, P4=0.020) expression. RT-PCR
      results showed that ABCG2, P-gp and vimentin mRNA were highly expressed in
      residual breast cancer tissue after chemotherapy. The expression of ABCG2 and P
      gp mRNA correlated positively with vimentin mRNA (r1=0.99, r2=0.96, P<0.05) but
      negatively with E-cadherin protein (r3=-0.99, r4=-0.98, P<0.05); Western blot
      showed that ABCG2, P-gp and vimentin protein were highly expressed in residual
      breast cancer tissue after chemotherapy. The expression of ABCG2 and P-gp protein
      correlated positively with vimentin protein (r1=0.98, r2=0.89, P<0.05) and
      negatively with E-cadherin protein (r3=-0.47, r4=-0.33, P<0.05). CONCLUSIONS: The
      expression of resistance-associated proteins in the residual breast cancer tissue
      after chemotherapy is significantly correlated with EMT. The expression of EMT
      profile may be one of important mechanisms for multidrug resistance in breast
      cancer.

PMID- 24915814
TI  - [Clinicopathologic correlation and ALK rearrangement in adenocarcinoma of lung].
AB  - OBJECTIVE: To investigate ALK gene rearrangements in lung adenocarcinomas in
      correlation with clinicopathologic parameters including prognosis. METHODS:
      Fluorescence in situ hybridization (FISH) was used to detect ALK gene
      rearrangements in 53 cases of lung adenocarcinomas. Mutations in exons 18, 19, 20
      and 21 of EGFR were analyzed by Scorpion amplification refractory mutation system
      (Scorpions ARMS). RESULTS: In a cohort of 53 lung adenocarcinomas, ALK gene
      rearrangements were identified in 6 tumors (11.3%), including 4 male and 2 female
      patients. Five were acinar predominant adenocarcinomas and one was mucinous
      adenocarcinoma (P=1.000). All tumors with the ALK rearrangements had the wild
      type epidermal growth factor receptor (EGFR) gene (P=0.023). The median time of
      disease-free survival (DFS) in ALK positive patients and negative patients were
      14 months (95%CI 8.0-20.0) and 31 months (95%CI 24.9-37.1), respectively and the
      difference was significant (Log-rank test, P=0.019). ALK gene rearrangements were
      significantly associated with early recurrence, but not tumor size, pathologic
      stages, histological differentiation and lymph node metastasis. CONCLUSIONS: ALK
      gene rearrangements are present at a higher frequency in lung adenocarcinomas of
      the Chinese patients. ALK gene rearrangements are mutually exclusive with EGFR
      mutations and associated with early tumor recurrence.

PMID- 24915815
TI  - [Significance of arginase-1, glypican-3, hepatocyte paraffin antigen 1 and alpha
      fetoprotein in diagnosis and differential diagnosis of liver tumors].
AB  - OBJECTIVE: To study the expression of arginase-1 (Arg-1), glypican-3 (GPC3),
      hepatocyte paraffin antigen 1 (HepPar-1) and alpha-fetoprotein (AFP) in
      hepatocellular carcinoma (HCC), benign liver lesions (BLL) and metastatic
      carcinoma (MC), and their applications in diagnosis and differential diagnosis.
      METHODS: Immunohistochemical study (EnVision method) for Arg-1, GPC3, HepPar-1
      and AFP was carried out in three groups of liver lesions, including 85 cases of
      HCC, 35 cases of BLL and 19 cases of MC. The relationship between expression of
      Arg-1, GPC3, HepPar-1 and AFP and clinicopathologic features in HCC was also
      analyzed. RESULTS: The positive expression rate of Arg-1 was 90.6% (79/85) in HCC
      and 100% (35/35) in BLL. Arg-1 expression was observed in 1 of the 19 cases of MC
      studied. The positive expression rate of GPC3 was 82.4% (70/85) in HCC, 5.3%
      (1/19) in MC and 0 (0/35) in BLL. The positive expression rate of AFP was 47.1%
      (40/85) in HCC and 0 in BLL or MC. The positive expression rate of HepPar-1 was
      72.9% (62/85) in HCC, 100% (35/35) in BLL and 2/19 in MC. Arg-1 has a higher
      sensitivity in highlighting hepatocellular lesions than AFP and HepPar-1 (P=0.000
      versus P=0.002). The specificity of GPC3 expression in HCC was 98.1%.
      CONCLUSIONS: Arg-1 is a sensitive hepatocellular marker in delineation of liver
      lesions.GPC3 is a relatively specific marker in diagnosis of HCC.

PMID- 24915816
TI  - [Correlation of caveolin-1 expression with clinicopathologic features and
      prognosis in patients with lung adenocarcinoma].
AB  - OBJECTIVE: To study the expression, clinicopathologic correlation and prognostic
      significance of caveolin-1 in lung adenocarcinomas(LAC). METHODS:
      Immunohistochemical study (EnVision method) for caveolin-1 and TTF-1 was carried
      out in 185 cases of LAC encountered during the period from 2005 to 2010. The
      correlation between caveolin-1 expression and various clinicopathologic
      parameters was analyzed statistically. RESULTS: The rate of caveolin-1 expression
      in the 185 cases of LAC was 26.5% (49/185) and significantly lower than that in
      normal lung tissue (P<0.01). There was also higher rate of caveolin-1 expression
      in male patients (P=0.004), smokers (P=0.006), tumors larger than 3.5 cm
      (P=0.048), predominantly solid tumor subtype (P=0.025), high tumor grade
      (P=0.044), tumors with vascular invasion (P=0.019), lymph node metastasis
      (P=0.030), recurrence (P=0.021) and high clinical stage (P=0.027). The expression
      level of caveolin-1 in TTF1-negative cases was significantly higher than that in
      TTF1-positive cases and caveolin-1 expression also negatively correlated with TTF
      1 expression in LAC (r=-0.154, P=0.037). The five-year overall survival rate of
      patients with caveolin-1 positive tumors was lower than that in caveolin-1
      negative group (P<0.01).Univariate analysis indicated the expression level of
      caveolin-1 and TTF-1 (P<0.01), histologic subtype (P=0.002), tumor grade
      (P=0.002), tumor size (P=0.009), vascular invasion (P=0.019), lymph node
      metastasis (P=0.018), recurrence (P=0.032) and clinical stage (P=0.024)
      correlated with the survival of patients with LAC. COX multivariate analysis
      revealed that LAC with caveolin-1 positive expression, TTF-1 negative expression
      and high tumor grade carried a significantly unfavorable prognosis. CONCLUSION:
      Caveolin-1 expression correlates with histologic subtype, tumor grade,
      invasiveness and metastatic potential of LAC. The detection of caveolin-1 in LAC
      is helpful in predicting prognosis.LAC with caveolin-1 expression carries a poor
      prognosis.

PMID- 24915817
TI  - [Nodular histiocytic/mesothelial hyperplasia: a clinicopathologic analysis of 7
      cases].
AB  - OBJECTIVE: To analyze the clinicopathologic and immunohistochemical features of
      nodular histiocytic/mesothelial hyperplasia (NHMH) and to improve the knowledge
      of this disease. METHODS: Seven cases of NHMH were collected and the
      clinicopathologic and immunohistochemical data were analyzed with review of the
      literature. RESULTS: Seven male patients aged from 1.5 to 5.0 years (mean 2.8).
      The main clinical symptom was an inguinal mass.Grossly, main pathological changes
      were the mural nodule or free nodule in lumen, with diameter of 0.1-0.5
      cm.Histologically, the tumor cell morphology was relatively single, cohesive
      polygonal or oval cells which were arranged in solid sheets or nests, usually
      with ovoid or deeply grooved nuclei and a moderate amount of pale pink cytoplasm
      in the nodular collection area. The nuclei had delicate chromatin and no obvious
      atypia, and mitosis was incidentally found. A few scattered lymphocytes were
      found in the stroma. The cyst wall was lined by a single layer of mesothelial
      cells.Immunohistochemically, the most cells in nodular lesion were strongly
      positive for the histiocytic marker CD68, vimentin and alpha1-antichymotrypsin,
      while lining mesothelial cells on the wall were positive for calretinin, MC, WT1,
      CK5/6, CKpan and EMA. CONCLUSIONS: NHMH is a rare and benign tumor-like lesion,
      and easy to be misdiagnozed, which should be distinguished from neuroendocrine
      tumors, Langerhans cell histiocytosis, seminoma, mesothelioma and so on. The
      correct diagnosis of this lesion depends on the clinical characteristics,
      morphology and immunohistochemistry.

PMID- 24915818
TI  - [Clinical and pathologic analysis of light-chain (AL) amyloidosis in 7 patients].

PMID- 24915819
TI  - [Guidelines for HER2 detection in breast cancer, the 2014 version].

PMID- 24915820
TI  - [The Chinese consensus on histopathology of inflammatory bowel disease].

PMID- 24915821
TI  - [Primary cardiac osteosarcoma: report of a case].

PMID- 24915822
TI  - [Granular cell tumor of appendix: report of a case].

PMID- 24915823
TI  - [Clear cell renal cell carcinoma with neuroendocrine differentiation and liver
      metastasis: report of a case].

PMID- 24915824
TI  - [Primary cutaneous perivascular epithelioid cell tumor: report of a case].

PMID- 24915825
TI  - [Progress of research on breast cancer stem cell markers].

PMID- 24915826
TI  - [Application of mass spectrometry imaging in tumor diagnosis and treatment].

PMID- 24915827
TI  - Nestin is a marker of lung remodeling secondary to myocardial infarction and type
      I diabetes in the rat.
AB  - Upregulation of the intermediate filament protein nestin was identified in a
      subpopulation of fibroblasts during reactive and reparative fibrosis and directly
      contributed to the enhanced proliferative phenotype. The present study tested the
      hypothesis that nestin was expressed in lung fibroblasts and the pattern of
      expression represented a distinct marker of pulmonary remodeling secondary to
      myocardial infarction and type I diabetes. Nestin((+)) fibroblasts were detected
      in rat lungs and a subpopulation exhibited a myofibroblast phenotype delineated
      by the co-expression of smooth muscle alpha-actin. In the lungs of myocardial
      infarcted rats, interstitial collagen content and nestin mRNA/protein levels were
      significantly increased despite the absence of secondary pulmonary hypertension,
      whereas smooth muscle alpha-actin protein expression was unchanged. Exposure of
      rat pulmonary fibroblasts to pro-fibrotic stimuli angiotensin II and transforming
      growth factor-beta significantly increased nestin protein levels. In the lungs of
      type I diabetic rats, the absence of a reactive fibrotic response was associated
      with a significant downregulation of nestin mRNA/protein expression. Nestin was
      reported a target of miR-125b, albeit miR-125b levels were unchanged in pulmonary
      fibroblasts treated with pro-fibrotic stimuli. Nestin((+)) cells lacking smooth
      muscle alpha-actin/collagen staining were also identified in rodent lungs and a
      transgenic approach revealed that expression of the intermediate filament protein
      was driven by intron 2 of the nestin gene. The disparate regulation of nestin
      characterized a distinct pattern of pulmonary remodeling secondary to myocardial
      infarction and type I diabetes and upregulation of the intermediate filament
      protein in lung fibroblasts may have facilitated in part the reactive fibrotic
      response.

PMID- 24915828
TI  - Isolation of the lateral border recycling compartment using a diaminobenzidine
      induced density shift.
AB  - The migration of leukocytes across the endothelium and into tissue is critical to
      mounting an inflammatory response. The lateral border recycling compartment
      (LBRC), a complex vesicular-tubule invagination of the plasma membrane found at
      endothelial cell borders, plays an important role in this process. Although a few
      proteins have been shown to be present in the LBRC, no unique marker is known.
      Here, we detail methods that can be used to characterize a subcellular
      compartment that lacks an identifying marker. Initial characterization of the
      LBRC was performed using standard subcellular fractionation with sucrose
      gradients and took advantage of the observation that the compartment migrated at
      a lower density than other membrane compartments. To isolate larger quantities of
      the compartment, we modified a classic technique known as a diaminobenzidine
      (DAB)-induced density shift. The DAB-induced density shift allowed for specific
      isolation of membranes labeled with horseradish peroxidase-conjugated antibody.
      Because the LBRC could be differentially labeled at 4  degrees C and 37  degrees
      C, we were able to identify proteins that are enriched in the compartment,
      despite lacking a unique marker. These methods serve as a model to others
      studying poorly characterized compartments and organelles and are applicable to a
      wide variety of biological systems.

PMID- 24915829
TI  - Bioactivity evaluation of ingredients identified from the fruits of Amomum tsaoko
      Crevost et Lemaire, a Chinese spice.
AB  - In this work, a phytochemical investigation was conducted on Amomum tsaoko
      Crevost et Lemaire, a traditional Chinese spice. Based on spectroscopic methods
      including MS, (1)H-NMR, (13)C-NMR, DEPT135 and HMQC spectroscopy, eight main
      chemical compositions, sitosterol, daucosterol, meso-hannokinol, quercetin,
      epicatechin, quercetin-7-O-beta-glucoside, quercetin-3-O-beta-glucoside, and
      catechol, were isolated and identified from A. tsaoko, among which quercetin,
      quercetin-7-O-beta-glucoside and quercetin-3-O-beta-glucoside were first found in
      A. tsaoko. Their bioactivities were evaluated by the inhibitory effect on NO
      production in LPS-stimulated macrophage RAW 264.7 cells, the protective effect on
      H2O2-induced apoptosis of PC-12 cells and the DPPH radical scavenging assay.
      Epicatechin exhibited excellent anti-inflammatory properties; its inhibition rate
      was up to 63.65% at a concentration of 100 MUg mL(-1). In addition, quercetin
      showed the strongest neuroprotective effect of PC-12 cells induced by H2O2, and
      the cell viability was up to 78.9% at a concentration of 50 MUg mL(-1). Quercetin
      also exhibited excellent DPPH radical-scavenging activity at a concentration of
      100 MUg mL(-1) (DPPH radical inhibition rate > 80%), which was very close to Vc
      at the same concentration. It is concluded that, in A. tsaoko, different
      ingredients have their own health functions. 

PMID- 24915830
TI  - 'Active play may be lots of fun, but it's certainly not frivolous': the emergence
      of active play as a health practice in Canadian public health.
AB  - In the context of what has been termed a childhood obesity epidemic, public
      health institutions have recently begun to promote active play as a means of
      addressing childhood obesity, thus advancing play for health. Drawing on
      Foucault, this article problematises the way that children's play is being taken
      up as a health practice and further considers some of the effects this may have
      for children. Six Canadian public health websites were examined, from which 150
      documents addressing children's health, physical activity, obesity, leisure
      activities and play were selected and coded deductively (theoretical themes) and
      inductively (emerging themes). Bacchi's () question-posing approach to critical
      discourse analysis deepened our analysis of dominant narratives. Our findings
      suggest that several taken-for-granted assumptions and practices underlie this
      discourse: (i) play is viewed as a productive activity legitimises it as a health
      practice; (ii) tropes of 'fun' and 'pleasure' are drawn on to promote physical
      activity; (iii) children are encouraged to self-govern their leisure time to
      promote health. We underscore the need to recognise this discourse as contingent
      and as only one of many ways of conceptualising children's leisure activities and
      their health and social lives more generally. 

PMID- 24915831
TI  - Limonoids from the fruits of Cipadessa cinerascens.
AB  - A new limonoid, 3-de(2-methylbutanoyl)-3-propanoylcipadesin (1), along with 10
      known limonoids and 1 known triterpenoid, was isolated from the fruits of
      Cipadessa cinerascens. Their structures were elucidated on the basis of
      spectroscopic analysis. All compounds were evaluated for their antimicrobial
      activities, and compounds 6 and 12 showed weak antimicrobial activities against
      MRSA 82(#) and MRSA 92(#). 

PMID- 24915832
TI  - Ultrafluorogenic coumarin-tetrazine probes for real-time biological imaging.
AB  - We have developed a series of new ultrafluorogenic probes in the blue-green
      region of the visible-light spectrum that display fluorescence enhancement
      exceeding 11,000-fold. These fluorogenic dyes integrate a coumarin fluorochrome
      with the bioorthogonal trans-cyclooctene(TCO)-tetrazine chemistry platform. By
      exploiting highly efficient through-bond energy transfer (TBET), these probes
      exhibit the highest brightness enhancements reported for any bioorthogonal
      fluorogenic dyes. No-wash, fluorogenic imaging of diverse targets including cell
      surface receptors in cancer cells, mitochondria, and the actin cytoskeleton is
      possible within seconds, with minimal background signal and no appreciable
      nonspecific binding, opening the possibility for in vivo sensing.

PMID- 24915833
TI  - Beyond pregnancy: modulation of trophoblast invasion and its consequences for
      fetal growth and long-term children's health.
AB  - Invasion of extravillous trophoblast cells (EVTs) into the maternal tissues is a
      key step in the development of a successful pregnancy, excessive and insufficient
      EVT invasion being associated with pregnancy complications. These pregnancy
      complications include preeclampsia and fetal growth restriction, both of which
      are associated with maternal and fetal morbidity and mortality at the time of
      birth and with increased risk of cardiovascular disease, diabetes and obesity in
      adult life for infants born from these conditions. In addition, women who develop
      preeclampsia are also at a greater risk of cardiovascular disease in later life.
      Many factors, protein and environmental, have been shown to both up- and down
      regulate this process in vitro via different mechanisms. The redundancy observed
      in the regulation of this system suggests that dysregulation of one factor may
      not contribute to the pathological conditions of EVT invasion and that the
      relative local concentrations of many different factors may be more important.
      This review article explores the possibility that the modulation of EVT invasion
      as a therapeutic target for pregnancies affected by preeclampsia and fetal growth
      restriction may not be possible or needs to concentrate on the modulation of cell
      activity as a whole and not of one particular factor.

PMID- 24915834
TI  - Chronic morphine and tramadol re-exposure induced an anti-anxiety effect in
      prepubertal rats exposed neonatally to the same drugs.
AB  - Anxiety disorders are among the most common mental disorders. Drugs that are
      often administered to manage medical problems cause rebound anxiety. The use of
      morphine and tramadol has increased in recent decades. In the present study, the
      effects of morphine and tramadol exposure during the neonatal and prepubertal
      periods on anxiety-like behaviours in prepubertal rats were investigated. Male
      neonate rats were injected subcutaneously with saline, morphine or tramadol (3-21
      mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were
      divided into seven groups (saline/saline, saline/tramadol, saline/morphine,
      tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and
      were injected with saline, tramadol or morphine for seven consecutive days. All
      rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27
      (chronic effects) and P29. Locomotor activity was increased by the second and
      third exposure to the EPM. Re-exposure to chronic morphine and tramadol resulted
      in increased locomotor activity, whereas acute and chronic administration of
      these drugs induced no notable difference. Anxiety decreased markedly after re
      exposure to tramadol and this anxiolytic-like behaviour was more dominant in EPM
      re-exposure in rats that had received higher doses of tramadol. Re-exposure to
      tramadol elicited a stronger anxiolytic-like behaviour than re-exposure to
      morphine. It can be concluded that repeated morphine and tramadol administration
      during the neonatal period followed by re-exposure to these drugs at an immature
      stage produces considerable anxiolytic-like behaviour. Exposure to chronic
      morphine and tramadol during the neonatal period may affect the developing brain,
      which may induce long-term changes in the opioid response. 

PMID- 24915835
TI  - Colloidal beading: sonication-induced stringing of selenium particles.
AB  - We report the preparation of monodispersed Se colloidal aggregates (dimers and
      trimers) via sonication-induced aggregation of spherical monomers. Control over
      the size and morphology of the products was achieved by changing the aging and
      sonication times, respectively. The possible mechanisms for the formation of
      colloidal aggregates were discussed. This method can provide a simple and
      versatile approach to the production of colloidal molecules of particles composed
      of different materials, which will be useful for fundamental studies related to
      colloidal systems. 

PMID- 24915836
TI  - Cryogels-versatile tools in bioseparation.
AB  - Cryogels are polymeric materials formed from monomeric or polymeric precursors in
      moderately frozen state by polymerization or crosslinking. The process applied
      for cryogel formation is called cryogelation. These macroporous gel matrices can
      be produced with different shapes and the gels are of interest in the
      bioseparation area since they can meet needs that conventional chromatographic
      media are less suitable to fulfill. High porosity, high mechanical and chemical
      stability make them appropriate carriers for immobilization of biomolecules and
      cells thereby making them attractive gel matrices for separation and purification
      of various molecules. This review highlights the preparation and properties of
      cryogels, and applications of these materials especially in bioseparation
      science. 

PMID- 24915837
TI  - Stability and change in sustainability of daily routines and social networks in
      families of children with profound intellectual and multiple disabilities.
AB  - BACKGROUND: Children with profound intellectual and multiple disabilities (PIMD)
      demand intense family accommodations from birth and onwards. This study used an
      exploratory and qualitative study design to investigate stability and change in
      sustainability of daily routines and social networks of Swedish families of
      children with PIMD. MATERIALS AND METHODS: Eight families participated over two
      years in eco-cultural family interviews and social networks interviews collected
      at home visits. Data were analyzed descriptively and by manifest contents
      analysis. RESULTS: Results showed variations in sustainability of daily routines
      over time across families. The sustainability was linked to fathers' involvement,
      couples' connectedness and emotional support. Stability and change of social
      networks were characterized by low overlap between the child and family networks,
      the children's communicative dependency and low density of able communication
      partners. CONCLUSIONS: The results indicate that patterns of stability and change
      were linked both to family resources and child characteristics.

PMID- 24915838
TI  - Conversion to lacosamide monotherapy in the treatment of focal epilepsy: results
      from a historical-controlled, multicenter, double-blind study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of conversion to lacosamide 400
      mg/day monotherapy in adults with focal epilepsy. METHODS: This historical
      controlled, double-blind study (NCT00520741) enrolled patients aged 16-70 years
      on stable doses of 1-2 antiepileptic drugs (AEDs) and experiencing 2-40 partial
      onset seizures per 28 days during the 8-week prospective Baseline. Patients were
      randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day
      and titrated over 3 weeks to randomized dose. Patients then withdrew background
      AEDs over 6 weeks and entered a 10-week Monotherapy Phase. The primary assessment
      was the Kaplan-Meier-predicted percentage of patients on 400 mg/day in the full
      analysis set (FAS) meeting >= 1 predefined seizure-related exit criterion by day
      112, compared with the historical-control threshold (65.3%). RESULTS: Four
      hundred twenty-five patients were enrolled and were eligible for safety analyses
      (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425
      patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and
      Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82
      (28.9%) met >= 1 exit criterion; the Kaplan-Meier-predicted exit percentage at
      day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6-35.5%) was lower
      than the historical control. When exit events, withdrawal due to treatment
      emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were
      summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8-37.8%) was
      also lower than the historical control. Most patients receiving 400 mg/day
      reported some improvement on the Clinical Global Impression of Change (75.4%) and
      Patient Global Impression of Change (74.3%). Overall, the most common (>10%)
      TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion
      (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to
      moderate in intensity. Seventy-two patients (16.9%) discontinued due to TEAEs.
      Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs.
      SIGNIFICANCE: Lacosamide 400 mg/day monotherapy was effective, with a favorable
      safety profile in patients with focal epilepsy.

PMID- 24915839
TI  - Symptom persistence in a community cohort of women with interstitial
      cystitis/bladder pain syndrome (IC/BPS): 3-, 6-, 9-, and 12-month follow-up from
      the RICE cohort.
AB  - INTRODUCTION AND HYPOTHESIS: The persistence of interstitial cystitis/bladder
      pain syndrome (IC/BPS) symptoms has been described in women seeking medical care.
      The purpose of this study was to determine whether symptoms persist among a
      population-based sample of women. METHODS: A probability sample of US women was
      identified through a two-stage telephone screening process using the Research and
      Development (RAND) Interstitial Cystitis Epidemiology (RICE) high-sensitivity
      case definition. A randomly selected subgroup (n = 508) was enrolled in a
      longitudinal study and interviewed about their symptoms at baseline, 3, 6, 9, and
      12 months. Bivariate and multivariate linear regression analyses determined
      predictors of persistence of symptoms over the four waves. RESULTS: A total of
      436 women with a mean age of 47.5 years responding to all waves were included in
      the analysis. Forty-one percent met the RICE high-sensitivity case definition at
      baseline and in all four waves; an additional 21 % met the definition at baseline
      and in three waves. Women with a college degree (+12 % vs. no college, p = 0.02)
      and who were younger (-5 % per decade of age, p < 0.01) had higher chances of
      symptom persistence at each wave. Scoring one standard deviation higher on the
      continuity of symptoms and the O'Leary-Sant Interstitial Cystitis Symptom index
      increased the chances of symptom persistence by 4 % and 2 %, respectively (both p
      < 0.01). CONCLUSIONS: The majority of women demonstrated symptom persistence
      across at least three of four waves over 12 months. These women tended to be
      younger, college-educated, and to have reported a history of greater continuity
      of symptoms and higher severity of symptoms at baseline.

PMID- 24915840
TI  - Comparison of pelvic muscle architecture between humans and commonly used
      laboratory species.
AB  - INTRODUCTION AND HYPOTHESIS: Pelvic floor muscles (PFM) are deleteriously
      affected by vaginal birth, which contributes to the development of pelvic floor
      disorders. To mechanistically link these events, experiments using animal models
      are required, as access to human PFM tissue is challenging. In choosing an animal
      model, a comparative study of PFM design is necessary, since gross anatomy alone
      is insufficient to guide the selection. METHODS: Human PFM architecture was
      measured using micromechanical dissection and then compared with mouse (n = 10),
      rat (n = 10), and rabbit (n = 10) using the Architectural Difference Index (ADI)
      (parameterizing a combined measure of sarcomere length-to-optimal-sarcomere
      ratio, fiber-to-muscle-length ratio, and fraction of total PFM mass and
      physiological cross-sectional area (PCSA) contributed by each muscle). Coccygeus
      (C), iliocaudalis (IC), and pubocaudalis (PC) were harvested and subjected to
      architectural measurements. Parameters within species were compared using
      repeated measures analysis of variance (ANOVA) with post hoc Tukey's tests. The
      scaling relationships of PFM across species were quantified using least-squares
      regression of log-10-transformed variables. RESULTS: Based on the ADI, rat was
      found to be the most similar to humans (ADI = 2.5), followed by mouse (ADI =
      3.3). When animals' body mass was regressed against muscle mass, muscle length,
      fiber length, and PCSA scaling coefficients showed a negative allometric
      relationship or smaller increase than predicted by geometric scaling. CONCLUSION:
      In terms of muscle design among commonly used laboratory animals, rat best
      approximates the human PFM, followed by mouse. Negative allometric scaling of PFM
      architectural parameters is likely due to the multifaceted function of these
      muscles.

PMID- 24915842
TI  - Nickel-catalysed carboxylation of organoboronates.
AB  - A nickel/N-heterocyclic carbene (NHC) catalysed carboxylation of aryl-,
      heteroaryl- and alkenylboronates, affording the corresponding carboxylic acids,
      has been developed. This transformation proceeds under one atmosphere of CO2 with
      a broad range of substrates and exhibits good functional group compatibility. 

PMID- 24915841
TI  - Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by
      maintaining redox balance.
AB  - To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial
      injury by mitochondrial dysfunction and increased oxidative stress in the kidney,
      3-week-old Bmi-1(-/-) mice were treated with the antioxidant N-acetylcysteine
      (NAC, 1 mg mL(-1) ) in their drinking water, or pyrro-quinoline quinone (PQQ, 4
      mg kg(-1) diet) in their diet for 2 weeks, and their renal phenotypes were
      compared with vehicle-treated Bmi1(-/-) and wild-type mice. Bmi-1 was knocked
      down in human renal proximal tubular epithelial (HK2) cells which were treated
      with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control
      cells. Five-week-old vehicle-treated Bmi-1(-/-) mice displayed renal interstitial
      fibrosis, tubular atrophy, and severe renal function impairment with decreased
      renal cell proliferation, increased renal cell apoptosis and senescence, and
      inflammatory cell infiltration. Impaired mitochondrial structure, decreased
      mitochondrial numbers, and increased oxidative stress occurred in Bmi-1(-/-)
      mice; subsequently, this caused DNA damage, the activation of TGF-beta1/Smad
      signaling, and the imbalance between extracellular matrix synthesis and
      degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of
      renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All
      phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant
      treatment. These findings indicate that Bmi-1 plays a critical role in protection
      from renal tubulointerstitial injury by maintaining redox balance and will be a
      novel therapeutic target for preventing renal tubulointerstitial injury.

PMID- 24915843
TI  - Effects of naringin on the proliferation and osteogenic differentiation of human
      amniotic fluid-derived stem cells.
AB  - Human amniotic fluid-derived stem cells (hAFSCs) are a novel cell source for
      generating osteogenic cells to treat bone diseases. Effective induction of
      osteogenic differentiation from hAFSCs is critical to fulfil their therapeutic
      potential. In this study, naringin, the main active compound of Rhizoma drynariae
      (a Chinese herbal medicine), was used to stimulate the proliferation and
      osteogenic differentiation of hAFSCs. The results showed that naringin enhanced
      the proliferation and alkaline phosphatase activity (ALP) of hAFSCs in a dose
      dependent manner in the range 1-100 ug/ml, while an inhibition effect was
      observed at 200 ug/ml. Consistently, the calcium content also increased with
      naringin concentration up to 100 ug/ml. The enhanced osteogenic differentiation
      of hAFSCs by naringin was further confirmed by the dose-dependent upregulation of
      marker genes, including osteopontin (OPN) and Collagen I from RT-PCR analysis.
      The increased osteoprotegerin (OPG) expression and minimal expression of receptor
      activator of nuclear factor-kappaB ligand (RANKL) suggested that naringin also
      inhibited osteoclastogenesis of hAFSCs. In addition, the gene expressions of bone
      morphogenetic protein 4 (BMP4), runt-related transcription factor 2 (RUNX2), beta
      catenin and Cyclin D1 also increased significantly, indicating that naringin
      promotes the osteogenesis of hAFSCs via the BMP and Wnt-beta-catenin signalling
      pathways. These results suggested that naringin can be used to upregulate the
      osteogenic differentiation of hAFSCs, which could provide an attractive and
      promising treatment for bone disorders. Copyright (c) 2014 John Wiley & Sons,
      Ltd.

PMID- 24915844
TI  - Management of peritoneal carcinomatosis from colorectal cancer: review of the
      literature.
AB  - BACKGROUND: Today, we do not have a universally accepted evidence on how to treat
      peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in international
      guidelines. METHODS: The present study is a review of the literature
      investigating current strategies to treat CRC PC. RESULTS: Despite the progresses
      of systemic chemotherapy, the presence of PC among patients with metastatic CRC
      reduces the overall survival to 30 %, and only 4 % of patients with PC from CRC
      treated are alive for 5 years. Many trials evaluate the combined treatment of
      cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
      for CRC PC, suggesting a survival benefit in highly selected patients. Only one
      trial is randomized and presents some biases. The two main prognostic factors are
      Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC score).
      There is no universal agreement on how to approach the synchronous presence of PC
      and liver metastasis with a curative intent during the same procedure. A growing
      interest among the scientific community has arisen about systematic second-look
      surgery and HIPEC treatment in high-risk patients. CONCLUSION: Current evidences
      suggest that CRS and HIPEC might be beneficial in highly selected patients
      affected with PC from CRC. Anyway, today, there is a shortage of well-designed
      phase 3 trials.

PMID- 24915845
TI  - Colon diversion versus primary colonic repair in gunshot abdomen with penetrating
      colon injury in Libyan revolution conflict 2011 (a single center experience).
AB  - PURPOSE: The objective of this study is comparing colon diversion versus primary
      repair in penetrating colon gunshot injuries. METHODS: A retrospective study of
      63 cases of gunshot abdomen with penetrating colon injury were admitted to Al
      jalla Hospital in 2011 in Benghazi, Libya. After surgical intervention, these
      patients were observed for any postoperative complications. RESULTS: During the
      study period, 63 eligible patients included, 62 (98.4%) were males and 1 (1.6%)
      was female. And the mean age was 29.24 years. Eighteen patients had an injury on
      the right side of the colon, while 16, 6, 11, 6, 2, 3, and 1 patients had an
      injury on the transverse, left, sigmoid, rectum, right transverse, left
      transverse, and total colonic injury, respectively. In the first group, 23
      patients (36.5%) was treated with colon diversion, (2 with Hartmann's operation,
      21 with loop colostomy). In the second group, 40 patients (63.4 %) was treated
      with primary repair. Eighteen (28.5%) with right hemicolectomy, 5 (7.9%) with
      transverse colon resection and anastomosis, and 17 (26.9%) with simple repair. We
      evaluate the rate of postoperative complication and compare the postoperative
      morbidity between both groups. CONCLUSION: In our study, there was no significant
      statistical difference between types of operations and rate of complications (P =
      0.18). We could not see any advantage of the diversion over the primary repair.
      To reduce risk of the psychological trauma, complications of colostomy,
      unnecessary repeated hospitalization, decrease of economic cost, and
      complications of stoma revision operation, we should consider that the primary
      repair of penetrating colon injuries is an acceptable alternative method of
      treatment over the colostomy.

PMID- 24915846
TI  - Rapid brain death caused by a cerebellar abscess with Fusobacterium nucleatum in
      a young man with drug abuse: a case report.
AB  - BACKGROUND: Fusobacterium nucleatum is a strict anaerobic microorganism that
      causes disease entities such as periodontal and soft tissue abscesses, pulmonary
      and intraabdominal infections and very rarely intracerebral infections. CASE
      PRESENTATION: Here, we report the rare case of a previously healthy 25-year-old
      German man with a cerebellar abscess caused by Fusobacterium nucleatum that
      resulted in rapid brain death. Toxicological screening showed positivity for
      amphetamines and cannabis. The diagnosis was obtained by polymerase chain
      reaction amplification of bacterial deoxyribonucleic acid in cerebrospinal fluid.
      CONCLUSIONS: In drug users clinicians should think about rare causes of brain
      abscesses/meningitis. Early diagnosis is necessary and justifies the use of
      molecular techniques.

PMID- 24915847
TI  - Functional connectivity changes between parietal and prefrontal cortices in
      primary insomnia patients: evidence from resting-state fMRI.
AB  - BACKGROUND: Primary insomnia can severely impair daytime function by disrupting
      attention and working memory and imposes a danger to self and others by
      increasing the risk of accidents. We speculated that the neurobiological changes
      impeding working memory in primary insomnia patients would be revealed by resting
      state functional MRI (R-fMRI), which estimates the strength of cortical pathways
      by measuring local and regional correlations in blood oxygen level dependent
      (BOLD) signs independent of specific task demands. METHODS: We compared the R
      fMRI activity patterns of 15 healthy controls to 15 primary insomnia patients
      (all 30 participants were right-handed) using a 3.0 T MRI scanner. The SPM8 and
      REST1.7 software packages were used for preprocessing and analysis. Activity was
      expressed relative to the superior parietal lobe (SPL, the seed region) to reveal
      differences in functional connectivity to other cortical regions implicated in
      spatial working memory. RESULT: In healthy controls, bilateral SPL activity was
      associated with activity in the posterior cingulate gyrus, precuneus,
      ventromedial prefrontal cortex, and superior frontal gyrus, indicating functional
      connectivity between these regions. Strong functional connectivity between the
      SPL and bilateral pre-motor cortex, bilateral supplementary motor cortex, and
      left dorsolateral prefrontal cortex was observed in both the control group and
      the primary insomnia group. However, the strength of several other functional
      connectivity pathways to the SPL exhibited significant group differences.
      Compared to healthy controls, connectivity in the primary insomnia group was
      stronger between the bilateral SPL and the right ventral anterior cingulate
      cortex, left ventral posterior cingulate cortex, right splenium of the corpus
      callosum, right pars triangularis (right inferior frontal gyrus/Broca's area),
      and right insular lobe, while connectivity was weaker between the SPL and right
      superior frontal gyrus (dorsolateral prefrontal cortex). CONCLUSION: Primary
      insomnia appears to alter the functional connectivity between the parietal and
      frontal lobes, cortical structures critical for spatial and verbal working
      memory.

PMID- 24915848
TI  - Survival analysis of patients with non-small cell lung cancer who underwent
      surgical resection following 4 lung cancer resection guidelines.
AB  - BACKGROUND: To compare survival of patients with non-small cell lung cancer
      (NSCLC) who underwent surgical resection and lymph node sampling based on
      guidelines proposed by the American College of Surgeons Oncology Group (ACOSOG),
      National Comprehensive Cancer Network (NCCN), the OSI Pharmaceutical RADIANT
      trial, and the International Association for the Study of Lung Cancer (IASLC).
      METHODS: Medical records of patients with NSCLC who underwent surgical resection
      from 2001 to 2008 at our hospital were reviewed. Staging was according to the 7th
      edition of the AJCC TNM classification of lung cancer. Patients who received
      surgical resection following the IASLC, ACOSOG, RADIANT or NCCN resection
      criteria were identified. RESULTS: A total of 2,711 patients (1803 males, 908
      females; mean age, 59.6 +/- 9.6 years) were included. Multivariate Cox
      proportional hazards regression analysis indicated that increasing age,
      adenosquamous histology, and TNM stage II or III were associated with decreased
      overall survival (OS). Univariate analysis and log-rank test showed that surgical
      resection following the guidelines proposed by the IASLC, NCCN, ACOSOG, or
      RADIANT trial was associated with higher cumulative OS rates (relative to
      resection not following the guidelines). Multivariate analysis revealed that
      there was a significant improvement in OS only when IASLC resection guidelines
      (complete resection) were followed (hazard ratio=0.84, 95% confidence interval
      0.716 to 0.985, P=0.032). CONCLUSIONS: Surgical resection following the criteria
      proposed by IASLC, NCCN, ACOSOG, or the RADIANT trial was associated with a
      higher cumulative OS rate. However, significant improvement in OS only occurred
      when IASLC resection guidelines were followed.

PMID- 24915849
TI  - Conventional and novel peripheral blood iron markers compared against bone marrow
      in Malawian children.
AB  - AIM: Iron deficiency is an important child health problem. Its diagnosis in areas
      of high infection exposure remains complicated as inflammation may interfere with
      the accuracy of peripheral iron markers. With this study, we aimed to validate
      the conventional iron markers and two novel iron markers, hepcidin and Red blood
      cell Size Factor (RSf), against the reference standard of iron status, bone
      marrow iron, in children living in an infectious setting. METHODS: We compared
      ferritin, soluble transferrin receptor, Soluble Transferrin Log-Ferritin Index
      (sTfR-F), mean cellular volume, mean cellular haemoglobin concentration, hepcidin
      and RSf, against bone marrow iron in 87 healthy Malawian children (6-66 months)
      scheduled for elective surgery. RESULTS: Of all children, 44.8% had depleted bone
      marrow iron stores. Using optimised cut-offs, ferritin (<18 ug/L) and sTfR-F
      (>1.85) best predicted depleted iron stores with a sensitivity/specificity of
      73.7%/77.1% and 72.5%/75.0%, respectively. Hepcidin (<1.4 nmol/L) was a moderate
      sensitive marker (73.0%) although specificity was 54.2%; RSf poorly predicted
      depleted iron stores. CONCLUSIONS: We provide the first bone marrow-validated
      data on peripheral iron markers in African children, and showed ferritin and sTfR
      F best predicted iron status. Using appropriately defined cut-offs, these
      indicators can be applied in surveillance and research. As their accuracy is
      limited for clinical purposes, more reliable iron biomarkers are still required
      in African children.

PMID- 24915850
TI  - Combined sputum hypermethylation and eNose analysis for lung cancer diagnosis.
AB  - AIMS: The aim of this study is to explore DNA hypermethylation analysis in sputum
      and exhaled breath analysis for their complementary, non-invasive diagnostic
      capacity in lung cancer. METHODS: Sputum samples and exhaled breath were
      prospectively collected from 20 lung cancer patients and 31 COPD controls (Set
      1). An additional 18 lung cancer patients and 8 controls only collected exhaled
      breath as validation set (Set 2). DNA hypermethylation of biomarkers RASSF1A,
      cytoglobin, APC, FAM19A4, PHACTR3, 3OST2 and PRDM14 was considered, and
      breathprints from exhaled breath samples were created using an electronic nose
      (eNose). RESULTS: Both DNA hypermethylation markers in sputum and eNose were
      independently able to distinguish lung cancer patients from controls. The
      combination of RASSF1A and 3OST2 hypermethylation had a sensitivity of 85% with a
      specificity of 74%. eNose had a sensitivity of 80% with a specificity of 48%.
      Sensitivity for lung cancer diagnosis increased to 100%, when RASSF1A
      hypermethylation was combined with eNose, with specificity of 42%. Both methods
      showed to be complementary to each other (p<=0.011). eNose results were
      reproducible in Set 2. CONCLUSIONS: When used in concert, RASSF1A
      hypermethylation in sputum and exhaled breath analysis are complementary for lung
      cancer diagnosis, with 100% sensitivity in this series. This finding should be
      further validated.

PMID- 24915851
TI  - Orthodontic treatment of children/adolescents with special health care needs: an
      analysis of treatment length and clinical outcome.
AB  - BACKGROUND: The aim of this retrospective study was to analyse the treatment time
      and differences between the pre- and post-treatment peer assessment rating (PAR)
      index and aesthetic component (AC) of the index of orthodontic treatment need
      (IOTN) scores in children/adolescents with special health care needs (SHCNs),
      compared to non-special health care needs (NSHCNs) controls. METHODS: Based on
      certain inclusion and exclusion criteria, medical records of SHCNs and randomly
      selected NSHCNs controls at the Department of Orthodontics, University Hospital
      Muenster were analysed retrospectively for the treatment time, number of
      appointments, chair time ("moderate" or "considerable"), PAR scores, and AC
      scores. Sample size calculation, descriptive statistics, and explorative analyses
      were performed using the Mann-Whitney U Test. RESULTS: Twenty-nine children with
      SHCNs (21 boys, 9 girls; median age: 11 years, pre-treatment) and 29 children
      with NSHCNs (12 boys, 17 girls; median age: 12 years, pre-treatment) were
      enrolled in this study.The overall treatment time did not differ between the
      patient groups. However, more "considerable chair time" was needed for the SHCNs
      group compared to the control group (p < 0.05), whereas "moderate chair time" was
      more often needed in patients with NSHCNs (p = 0.001).The age of the patients at
      the first and last appointments showed significant statistical differences:
      children in the SHCNs group commenced orthodontic treatment earlier, by a median
      of 1 year, compared to children in the NSHCNs group.The SHCNs group had
      significantly higher pre- and post-treatment PAR scores (median 21/median 6) and
      AC scores (median 9/median 3) compared to NSHCNs patients (PAR: median 17/median
      0; AC: median 5/median 1).However, the overall treatment time and the overall PAR
      and AC score reduction did not differ significantly between the SHCNs and NSHCNs
      groups. CONCLUSIONS: While the overall treatment time and number of appointments
      did not differ, the overall chair time was higher in the SHCNs group. The pre-
      and post-treatment PAR and AC scores were significantly higher in the SHCNs
      group.

PMID- 24915852
TI  - Synergistic activity of phenazines isolated from Pseudomonas aeruginosa in
      combination with azoles against Candida species.
AB  - Candidiasis infections are caused by yeasts from the genus Candida. The types of
      infection range from superficial to systemic. Treatment often requires
      antifungals such as the azoles; however, increased use of these drugs has led to
      the generation of yeasts with increased resistance to these drugs. Here, we
      describe the synergistic anticandidal activity of three phenazines-phenazine-1
      ol, phenazine-1-carboxylic acid, and phenazine-1-carboxamide. These phenazines
      were purified from Pseudomonas aeruginosa in combination with three clinically
      used azoles-fluconazole, itraconazole, and clotrimazole. The synergistic
      anticandidal activities of phenazines and azoles were assessed using the
      checkerboard microdilution and time-kill methods. Study results show that the
      combined effects of phenazines and azoles were predominantly synergistic activity
      (fractional inhibitory concentration index <0.5). The time-kill study, which
      included a combination of the minimum inhibitory concentration of phenazines and
      azoles, showed growth of Candida species that was completely attenuated after 0-6
      h of treatment. These results, which suggest that the activity of phenazines and
      azoles may be beneficial, have potential implications in delaying the development
      of resistance, as the anticandidal effect is achieved with lower concentrations
      of both agents (phenazines and azoles). The cytotoxicity of phenazines was also
      tested against a normal human cell line (foreskin normal fibroblast). No
      cytotoxicity was recorded at concentrations up to 200 MUg/ml. The in vitro
      synergistic activity of phenazines and azoles against Candida species is reported
      here for the first time. 

PMID- 24915853
TI  - Evaluation of noninvasive methods for the diagnosis of fungal endocarditis.
AB  - Fungal endocarditis (FE) is an uncommon disease with a high risk of morbidity and
      mortality. Here, we evaluated the different methods for diagnosing this
      infection. Cardiac valve, vegetation, and embolic materials obtained during
      surgery were examined for fungal infections by direct smear and culture. At least
      two blood samples were inoculated at the bedside into BACTEC medium.
      Galactomannan, mannan Ag enzyme-linked immunosorbent assay, and real-time
      polymerase chain reaction (PCR) assay were performed with serum samples. Of 25
      patients with suspected infective endocarditis (IE), 8 were found to have proven
      FE according to the direct culture results. The etiologic agents were Aspergillus
      niger (three cases), A. flavus (two cases), A. fumigatus (one case), and Candida
      albicans (two cases). Blood culture was positive in only 1 case. The sensitivity,
      specificity, positive and negative predictive values, and positive and negative
      likelihood ratios of the results from the galactomannan test were 83.3%, 84.2%,
      62.5%, 94.1%, 5.3, and 0.2; these same values, obtained from real-time PCR, were
      87.5%, 94.4%, 87.5%, 94.4%, 15.6, and 0.14, respectively. Because mannan antigen
      was positive in samples from only one patient, we opted not to calculate the
      sensitivity. However, the specificity value in 23 cases without IE caused by
      Candida spp. was 100%. Based on our results, both the galactomannan test and real
      time PCR can serve as reliable, noninvasive tests for the diagnosis of FE,
      compared with culture, which is considered to be the gold standard. 

PMID- 24915854
TI  - The multimodal treatment of acromegaly: current status and future perspectives.
AB  - Acromegaly is a chronic systemic disorder caused by a GH-secreting pituitary
      adenoma. Active acromegaly results in a poor quality of life due to symptoms such
      as headache, fatigue, arthralgia, depression, sexual dysfunction and
      hyperhidrosis; an increased prevalence of co-morbidities like diabetes,
      hypertension as well as cancer risk and a reduced life expectancy. Appropriate,
      modern, multimodal treatment of acromegaly has led to a significant improvement
      in quality of life, an adequate control of co-morbidities and a drastic reduction
      in the mortality rates that used to prevail in the past. This multimodal strategy
      includes an adequate selection of patients who are likely to benefit from
      surgical treatment (which has to be performed by a skilled pituitary
      neurosurgeon), the use of pharmacological interventions such as somatostatin
      analogs and dopamine agonists, which target the pituitary adenoma; and
      pegvisomant, a GH mutant acting as a competitive antagonist of the GH receptor.
      Radiation therapy is an important tool, particularly in parts of the World where
      resources are limited. The ultimate outcome of the individual patient depends on
      the judicious use of all these treatment options, which are critically analyzed
      in this mini-review. 

PMID- 24915855
TI  - Outcomes after flap reconstruction for extremity soft tissue sarcoma: a case
      control study using propensity score analysis.
AB  - BACKGROUND: Because of the complexity of flap reconstruction and the magnitude of
      soft tissue defects, patients undergoing flap reconstruction for extremity soft
      tissue sarcoma (STS) may have increased morbidity and poor outcome compared with
      those undergoing primary closure. However, to examine the accurate impact of flap
      reconstruction on extremity STS patients, the potential bias by confounding
      factors should be minimized. METHODS: We used propensity score analysis to match
      37 patients who underwent flap reconstruction to 111 patients who underwent
      primary closure (1-3 ratio) based on patient and tumor characteristics at
      presentation. Treatment, functional, and oncologic outcomes were compared between
      the two groups. RESULTS: Flap reconstruction group showed a lower Musculoskeletal
      Tumor Society functional score (P < 0.001), higher wound complication rate (P <
      0.001), and longer hospital stay (P < 0.001); but had better local control (P =
      0.015) than the primary closure group. Although failing to reach the statistical
      significance, the flap group tended to secure a wider surgical margin than the
      primary closure group (P = 0.051). CONCLUSIONS: Patients who underwent flap
      reconstruction had increased morbidity associated with flap reconstruction, but
      better local control. These findings may have implications for treating extremity
      STS patients.

PMID- 24915856
TI  - The effect of age at diagnosis on prostate cancer mortality: a grade-for-grade
      and stage-for-stage analysis.
AB  - OBJECTIVE: To evaluate the effect of advancing age on cancer-specific mortality
      (CSM) after radical prostatectomy (RP). MATERIALS AND METHODS: Overall, 205,551
      patients with PCa diagnosed between 1988 and 2009 within the Surveillance
      Epidemiology and End Results (SEER) database were included in the study. Patients
      were stratified according to age at diagnosis: <= 50, 51-60, 61-70, and >= 71
      years. The 15-year cumulative incidence CSM rates were computed. Competing-risks
      regression models were performed to test the effect of age on CSM in the entire
      cohort, and for each grade (Gleason score 2-4, 5-7, and 8-10) and stage (pT2,
      pT3a, and pT3b) sub-cohorts. RESULTS: Advancing age was associated with higher 15
      year CSM rates (2.3 vs. 3.4 vs. 4.6 vs. 6.3% for patients aged <= 50 vs. 51-60
      vs. 61-70 vs. >= 71 years, respectively; P < 0.001). In multivariable analyses,
      age at diagnosis was a significant predictor of CSM. This relationship was also
      observed in sub-analyses focusing on patients with Gleason score 5-7, and/or pT2
      disease (all P <= 0.05). Conversely, age failed to reach the independent
      predictor status in men with Gleason score 2-4, 8-10, pT3a, and/or pT3b disease.
      CONCLUSIONS: Advancing age increases the risk of CSM. However, when considering
      patients affected by more aggressive disease, age was not significantly
      associated with higher risk of dying from PCa. In high-risk patients, tumor
      characteristics rather than age should be considered when making treatment
      decisions.

PMID- 24915857
TI  - Patterns, timing and risk factors of recurrence of gastric cancer after
      laparoscopic gastrectomy: reliable results following long-term follow-up.
AB  - BACKGROUND: To clarify the patterns, timing and risk factors of recurrence of
      gastric cancer after laparoscopic gastrectomy. METHODS: From January 1999 to
      March 2012, 577 patients underwent laparoscopic or laparoscopy-assisted
      gastrectomy for curative resection of gastric cancer. Recurrence patterns were
      classified as locoregional, hematogenous, peritoneal, distant lymph node and
      mixed. Recurrence patterns and time to recurrence were retrospectively examined
      and risk factors for recurrence were analyzed. RESULTS: Recurrence occurred in 28
      (4.9%) cases with patterns as follows: locoregional in 2 patients (7.1%),
      hematogenous in seven (25.0%), peritoneal in nine (32.1%), distant lymph node in
      four (14.3%), and mixed in 6 (21.4%). There was no recurrence pattern peculiar to
      laparoscopic surgery. Recurrence occurred at one site in 21 patients (78.6%), two
      in 4 patients (14.3%), and three in 2 patients (7.1%). The median time to
      recurrence was 384 days (range 83-1497 days). Recurrence was detected within a
      year in 13 cases (46.4%), within two years in 21 (75%), and within three years in
      25 (89.3%). Univariate analysis revealed tumor location, tumor size, type of
      operation, tumor depth, and lymph node classification as risk factors for
      recurrence. Multivariate analysis indicated tumor depth and lymph node
      classification as risk factors of recurrence. CONCLUSIONS: Patterns, timing and
      risk factors of recurrence of gastric cancer after laparoscopic gastrectomy are
      similar to those after open gastrectomy, with no peculiarities specific to
      laparoscopic gastrectomy. Thus, as long as laparoscopic gastrectomy is performed
      according to the present inclusion criteria, follow-up can be similarly performed
      as for open gastrectomy.

PMID- 24915858
TI  - Thyroid incidentalomas discovered on positron emission tomography CT scanning -
      Malignancy rate and significance of standardised uptake values.
AB  - AIMS: Increasing use of 18F-Fluorodeoxy glucose (FDG) Positron Emission
      Tomography Computed Tomography (PET CT) has resulted in an increased frequency of
      incidentally discovered areas of focally increased FDG uptake within the thyroid
      gland - thyroid incidentalomas. We aimed to compare radiological characteristics
      of thyroid incidentalomas with cytology, histology and ultrasound findings.
      MATERIALS AND METHODS: We examined all FDG PET CT scan reports for all patients
      undergoing this investigation over a 6 year period in a single tertiary cancer
      centre. All PET CT scans followed an agreed proforma allowing reports mentioning
      "thyroid" to be identified. Reports commenting on a positive finding within the
      thyroid gland were investigated further manually. Incidental mentions of thyroid
      with no underlying abnormality were discounted from analysis. RESULTS: In the
      study period, 7221 patients underwent FDG PET CT scanning in our unit. Within
      this group 75 (1%) showed diffuse FDG uptake and 81 (1.1%) showed focal uptake
      (thyroid incidentalomas). Only 30 patients (37%) with incidentalomas had further
      investigation and malignancy rate was 23% (7/30). Median Standardised Uptake
      Values (SUV) in malignant lesions was 9.9 (range 3.5-17.8) whilst in benign
      lesions and diffuse lesions it was 5.4 (2.8-32) and 4.2 (2.1-25.6) respectively
      (p = 0.0013, Kruskal Wallis). CONCLUSION: There remains a need to develop a
      standardised approach to the investigation and management of thyroid
      incidentalomas discovered on FDG PET CT scanning. Up to 1 in 4 of these patients
      will harbour thyroid malignancy.

PMID- 24915859
TI  - Selecting patients for a second hepatectomy for colorectal metastases: an
      systemic review and meta-analysis.
AB  - BACKGROUND: Opinions on the suitability of repeat hepatectomy for patients with
      recurrent colorectal liver metastases (CRLMs) vary among studies. We conducted a
      meta-analysis to establish the criteria for selecting the best candidates for a
      second hepatectomy. METHODS: Database and manual searches were performed to
      identify comparative or prognostic studies published up to October 2013. Outcomes
      of interest included disease characteristics, perioperative outcomes, and long
      term survival after initial and second hepatectomies for patients with CRLM.
      Study quality was appraised using the Newcastle-Ottawa scale and a modified
      Hayden's score. RESULTS: A total of 7226 patients from 27 studies were included.
      Recurrent CRLMs after initial hepatectomy were more likely to be solitary (RR =
      0.86, P = 0.045), unilobar (RR = 0.60, P < 0.001), and smaller (WMD = -0.66, P <
      0.001). Postoperative morbidity and mortality were comparable between initial and
      second hepatectomies (RR = 1.10, P = 0.191; RR = 0.78, P = 0.678, respectively).
      In high-quality studies, patients showed better survival after a second
      hepatectomy than those after a single hepatectomy (HR = 0.68, P = 0.022).
      Patients meeting the following six predictors survived longer after second
      hepatectomy: disease-free survival after initial hepatectomy >1 y (P = 0.034);
      solitary CRLM at second hepatectomy (P < 0.001); unilobar CRLM at second
      hepatectomy (P = 0.009); maximal size of CRLM at second hepatectomy <= 5 cm (P =
      0.035); lack of extrahepatic metastases at second hepatectomy (P < 0.001); and R0
      resection at second hepatectomy (P < 0.001). CONCLUSIONS: Second hepatectomy is a
      safe and feasible procedure for patients with recurrent CRLM. In fact, in well
      selected patients it improves overall survival. The established criteria can help
      clinicians to select the best candidates for second hepatectomy and to achieve
      better long-term outcomes after resection.

PMID- 24915860
TI  - Spot quantification in two dimensional gel electrophoresis image analysis:
      comparison of different approaches and presentation of a novel compound fitting
      algorithm.
AB  - BACKGROUND: Various computer-based methods exist for the detection and
      quantification of protein spots in two dimensional gel electrophoresis images.
      Area-based methods are commonly used for spot quantification: an area is assigned
      to each spot and the sum of the pixel intensities in that area, the so-called
      volume, is used a measure for spot signal. Other methods use the optical density,
      i.e. the intensity of the most intense pixel of a spot, or calculate the volume
      from the parameters of a fitted function. RESULTS: In this study we compare the
      performance of different spot quantification methods using synthetic and real
      data. We propose a ready-to-use algorithm for spot detection and quantification
      that uses fitting of two dimensional Gaussian function curves for the extraction
      of data from two dimensional gel electrophoresis (2-DE) images. The algorithm
      implements fitting using logical compounds and is computationally efficient. The
      applicability of the compound fitting algorithm was evaluated for various
      simulated data and compared with other quantification approaches. We provide
      evidence that even if an incorrect bell-shaped function is used, the fitting
      method is superior to other approaches, especially when spots overlap. Finally,
      we validated the method with experimental data of urea-based 2-DE of Abeta
      peptides andre-analyzed published data sets. Our methods showed higher precision
      and accuracy than other approaches when applied to exposure time series and
      standard gels. CONCLUSION: Compound fitting as a quantification method for 2-DE
      spots shows several advantages over other approaches and could be combined with
      various spot detection methods.The algorithm was scripted in MATLAB (Mathworks)
      and is available as a supplemental file.

PMID- 24915861
TI  - Diagnosis of Niemann-Pick disease type C with 7-ketocholesterol screening
      followed by NPC1/NPC2 gene mutation confirmation in Chinese patients.
AB  - BACKGROUND: It has been reported that oxidation product of cholesterol, 7
      ketocholesterol, increases in plasma of patients with NP-C. Previously, we
      established a rapid test to determine the plasma 7-ketocholesterol level and
      found it elevated significantly in patients with acid sphingomyelinase deficient
      NPD and NP-C disease. METHODS: Individuals randomly referred to our outpatient
      clinics in the past two years for hepatosplenomegaly or isolated splenomegaly,
      who have been excluded as acid sphingomyelinase deficient NPD or Gaucher disease,
      and individuals with newborn cholestasis, psychomotor regression/retardation,
      were screened for plasma 7-ketocholesterol level. Individuals with high 7
      ketocholesterol level were then analyzed for NPC1 and NPC2 gene mutation to
      confirm the accuracy of NP-C diagnosis. RESULTS: By screening the plasma 7
      ketocholesterol of suspect individuals, 12 out of 302 (4%) had shown remarkable
      high levels compared with reference. All these twelve individuals were
      subsequently confirmed to be NP-C by DNA analysis of NPC1 and NPC2 genes, with
      the early infantile form (n = 7), the late infantile form (n = 1), the juvenile
      form (n = 1) and the adult form (n = 1). Furthermore, two NP-C patients without
      observable neuropsychiatric disability were picked up through this procedure.
      Only one patient had NP-C due to NPC2 gene mutations, with the rest due to NPC1
      gene mutations. We found that in NP-C patients AST was usually mildly elevated
      and ALT was in a normal range when jaundice was not present. In total, 22 mutant
      alleles were identified in the NPC1 gene, including six novel small
      deletions/insertions, e.g., c.416_417insC, c.1030delT, c.1800delC,
      c.2230_2231delGT, c.2302_2303insG, and c.2795dupA; seven novel exonic point
      mutations, c.1502A>T (p.D501V), c.1553G>A (p.R518Q), c.1832A>G (p.D611G),
      c.2054T>C (p.I685T), c.2128C>T(p.Q710X), c.2177G>C (p.R726T), c.2366G>A
      (p.R789H), and one novel intronic mutation c.2912-3C>G. Small
      deletions/insertions constituted nearly half of the mutant alleles (10/22, 45%),
      indicating a unique mutation spectrum in this cohort of Chinese NP-C patients.
      CONCLUSION: Our data confirm in a clinical setting that screening plasma 7
      ketocholesterol is an efficient and practical diagnostic tool to identify NP-C
      patients from suspect individuals. Patients without neuropsychological
      involvement could also be identified by this method therefore allowing an
      opportunity for earlier treatment.

PMID- 24915863
TI  - Multi-disciplinary communication networks for skin risk assessment in nursing
      homes with high IT sophistication.
AB  - BACKGROUND: The role of nursing home (NH) information technology (IT) in quality
      improvement has not been clearly established, and its impacts on communication
      between care givers and patient outcomes in these settings deserve further
      attention. OBJECTIVES: In this research, we describe a mixed method approach to
      explore communication strategies used by healthcare providers for resident skin
      risk in NH with high IT sophistication (ITS). METHODS: Sample included NH
      participating in the statewide survey of ITS. We incorporated rigorous
      observation of 8- and 12-h shifts, and focus groups to identify how NH IT and a
      range of synchronous and asynchronous tools are used. Social network analysis
      tools and qualitative analysis were used to analyze data and identify
      relationships between ITS dimensions and communication interactions between care
      providers. RESULTS: Two of the nine ITS dimensions (resident care-technological
      and administrative activities-technological) and total ITS were significantly
      negatively correlated with number of unique interactions. As more processes in
      resident care and administrative activities are supported by technology, the
      lower the number of observed unique interactions. Additionally, four thematic
      areas emerged from staff focus groups that demonstrate how important IT is to
      resident care in these facilities including providing resident-centered care,
      teamwork and collaboration, maintaining safety and quality, and using
      standardized information resources. CONCLUSION: Our findings in this study
      confirm prior research that as technology support (resident care and
      administrative activities) and overall ITS increases, observed interactions
      between staff members decrease. Conversations during staff interviews focused on
      how technology facilitated resident centered care through enhanced information
      sharing, greater virtual collaboration between team members, and improved care
      delivery. These results provide evidence for improving the design and
      implementation of IT in long term care systems to support communication and
      associated resident outcomes.

PMID- 24915864
TI  - Magnet Hospitals: Higher Rates of Patient Satisfaction.
AB  - Patient satisfaction with care is an important indicator of quality of care. As
      of 2013-2014, 30% of the Value-Based Purchasing score Medicare is using to
      determine hospital reimbursement is based on patient reports of care. This study
      determined whether significant relationships exists between Magnet (N = 160),
      Magnet-in-progress (N = 99), and non-Magnet hospital (N = 1,742) status and the
      highest ratings on the Hospital Consumer Assessment of Healthcare Providers and
      Systems (HCAHPS) survey questions related to patient satisfaction with care. This
      study was a secondary analysis of data collected and compiled from three sources
      (the American Hospital Association, American Nurses Credentialing Center, and
      HCAHPS databases). Analysis revealed that Magnet and Magnet-in-progress hospitals
      have significantly (p < .007) higher scores than non-Magnet hospitals on six of
      the seven questions regarding patient-reported satisfaction with care. The
      implications of these results for nursing are discussed.

PMID- 24915862
TI  - Inflammasome activation in airway epithelial cells after multi-walled carbon
      nanotube exposure mediates a profibrotic response in lung fibroblasts.
AB  - BACKGROUND: In vivo studies have demonstrated the ability of multi-walled carbon
      nanotubes (MWCNT) to induce airway remodeling, a key feature of chronic
      respiratory diseases like asthma and chronic obstructive pulmonary disease.
      However, the mechanism leading to remodeling is poorly understood. Particularly,
      there is limited insight about the role of airway epithelial injury in these
      changes. OBJECTIVES: We investigated the mechanism of MWCNT-induced primary human
      bronchial epithelial (HBE) cell injury and its contribution in inducing a
      profibrotic response. METHODS: Primary HBE cells were exposed to thoroughly
      characterized MWCNTs (1.5-24 MUg/mL equivalent to 0.37-6.0 MUg/cm2) and MRC-5
      human lung fibroblasts were exposed to 1:4 diluted conditioned medium from these
      cells. Flow cytometry, ELISA, immunostainings/immunoblots and PCR analyses were
      employed to study cellular mechanisms. RESULTS: MWCNT induced NLRP3 inflammasome
      dependent pyroptosis in HBE cells in a time- and dose-dependent manner. Cell
      death and cytokine production were significantly reduced by antioxidants, siRNA
      to NLRP3, a caspase-1 inhibitor (z-WEHD-FMK) or a cathepsin B inhibitor (CA
      074Me). Conditioned medium from MWCNT-treated HBE cells induced significant
      increase in mRNA expression of pro-fibrotic markers (TIMP-1, Tenascin-C,
      Procollagen 1, and Osteopontin) in human lung fibroblasts, without a concomitant
      change in expression of TGF-beta. Induction of pro-fibrotic markers was
      significantly reduced when IL-1beta, IL-18 and IL-8 neutralizing antibodies were
      added to the conditioned medium or when conditioned medium from NLRP3 siRNA
      transfected HBE cells was used. CONCLUSIONS: Taken together these results
      demonstrate induction of a NLRP3 inflammasome dependent but TGF-beta independent
      pro-fibrotic response after MWCNT exposure.

PMID- 24915865
TI  - The Nursing Division of the Israeli Health Ministry Moves Nursing Into the
      Forefront of Health Care.
AB  - The Nursing Division of the Israeli Ministry of Health, with the Government
      Nursing Officer at its helm, plays a pivotal role in promoting the nursing
      profession and influencing national health policy. In terms of nursing, the
      division is authorized to set, upgrade, and audit professional standards; create
      new specialties; formulate, oversee, and accredit educational programs; and award
      license to practice. In terms of broad policy, it has a voice in shaping general
      health priorities and allocating resources. Through the strategic use of the
      Nursing Division's vested powers and in collaboration and consultation with
      stakeholders, current nursing roles are being expanded and new ones are being
      developed to meet the needs of the population. The aim of this article is to
      describe and analyze the contribution of the Nursing Division under leadership of
      the Government Nursing Officer in promoting nursing and health care in Israel
      over the last decade.

PMID- 24915866
TI  - Mixed-Method Nursing Research: "A Public and Its Problems?" A Commentary on
      French Nursing Research.
AB  - Nursing in France is undergoing a transition. In 2009, the preregistration
      nursing education program was reformed in line with the European Bologna Process,
      bringing nursing education to the universities. In 2010, the French Programme
      Hospitalier de Recherche Infirmiere, the first national French nursing research
      funding program, was launched by the French Health Ministry. Of the 149 French
      research proposals submitted by registered nurses in 2010 and 2011, 13 were mixed
      method proposals. The registered nurse principal investigator argued for a
      complementary use of qualitative and quantitative methods. These trends highlight
      major issues regarding mixed-method and nursing research. We can reasonably
      assume that mixed-method research has a broad appeal for nurse scholars,
      particularly for the exploration of complex phenomena related to nursing.
      Moreover, the recent movement in the domain of nursing education and research
      experienced in France highlights the need for dedicated research education in the
      development of nursing research capacity.

PMID- 24915867
TI  - Editorial.

PMID- 24915868
TI  - Adolescent urology.

PMID- 24915869
TI  - Use of non-invasive uroflowmetry with simultaneous electromyography to monitor
      patient response to treatment for lower urinary tract conditions.
AB  - OBJECTIVE: Non-invasive uroflowmetry with simultaneous electromyography
      (uroflow/EMG) has previously been reported as effective in triaging patients into
      four specific non-neurogenic lower urinary tract (LUT) conditions for targeted
      treatment. In this study we sought to determine if the same parameters would be
      useful for measuring response to treatment. MATERIAL AND METHODS: We reviewed our
      database of normal children with LUT dysfunction, screened with uroflow/EMG, and
      diagnosed with a LUT condition: (1) dysfunctional voiding (DV); (2) idiopathic
      detrusor overactivity disorder (IDOD); (3) detrusor underutilization disorder
      (DUD); (4) primary bladder neck dysfunction (PBND). Pre- and on-treatment
      (minimum 3 months) uroflow/EMG parameters and subjective improvements were
      compared. RESULTS: Of 159 children (71 boys, 88 girls; median age 7.0 years,
      range 3.5-18.0 years), median follow up was 13.1 months (range 3-43 months). On
      targeted treatment, DV patients showed relaxation of pelvic floor during voiding
      and significant decrease in PVR on biofeedback; IDOD patients had normalization
      of short lag time and increased capacity on antimuscarinics; DUD patients had a
      decrease in capacity on timed voiding; PBND patients on alpha-blocker therapy
      showed improved uroflow rates and a decrease in mean EMG lag time (all p < 0.05).
      CONCLUSION: Non-invasive uroflow/EMG is useful not only for diagnosing specific
      LUT conditions, but also in objectively monitoring treatment efficacy. Subjective
      improvement on targeted therapy correlates well with objective improvements in
      uroflow/EMG parameters lending validation to this simplified approach to
      diagnosis.

PMID- 24915870
TI  - Internalizing the threat of risk--a qualitative study about adolescents'
      experience living with screening-detected celiac disease 5 years after diagnosis.
AB  - BACKGROUND: Mass screening could identify those with unrecognized celiac disease
      (CD), but the experience of being detected through screening and living with
      screening-detected CD should be explored before considering this as acceptable
      intervention. For this study we invited screening-detected adolescents to
      describe their experience living with screening-detected CD five years after
      diagnosis with the aim to explore how their perceptions, practices, and beliefs
      evolved. METHODS: Adolescents who were diagnosed through a population-based CD
      screening were invited to write narratives after being diagnosed. Of 153
      adolescents who were eventually diagnosed through the screening, 91 wrote
      narratives one year after diagnosis and 72 five years after diagnosis. A
      qualitative content analysis resulted in a theme and categories that describe the
      experience living with screening-detected CD five years after diagnosis. RESULTS:
      The overall theme--Internalizing the threat of risk--illustrates that being
      detected through screening and the internalized threat of future health
      complications have impacted how these adolescents felt about the diagnosis, coped
      with the gluten-free diet (GFD), and thought about CD screening. This theme is
      supported by four categories: maintaining an imposed disease identity describes
      how they continued to define their diagnosis in relation to the screening. They
      also expressed moving from forced food changes to adapted diet routines by
      describing habits, routines, coping strategies, and the financial burden of the
      GFD. They had enduring beliefs of being spared negative consequences, however,
      even after five years, some doubted they had CD and worried that being detected
      and eating a GFD might not be beneficial, i.e. continuing to fear it is "all in
      vain". CONCLUSIONS: There was maintenance and evolution in the perceptions,
      practices, and beliefs of the adolescents after five years. Some have adjusted to
      the disease and adapted new habits and coping strategies to deal with the GFD,
      while others still doubt they have CD or that being detected was beneficial. The
      transition to adapting to the disease and GFD is ongoing, illustrating the
      importance of providing ongoing support for those with screening-detected CD as
      they adjust to this chronic disease and the GFD.

PMID- 24915871
TI  - History of chronic comorbidity and risk of chemotherapy-induced febrile
      neutropenia in cancer patients not receiving G-CSF prophylaxis.
AB  - BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is a clinically
      important complication that affects patient outcome by delaying chemotherapy
      doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient
      level factors. We sought to determine the effects of chronic comorbidities on
      risk of FN. DESIGN: We conducted a cohort study to examine the association
      between a variety of chronic comorbidities and risk of FN in patients diagnosed
      with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung,
      ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy
      at Kaiser Permanente Southern California, a large managed care organization. We
      excluded those patients who received primary prophylactic granulocyte colony
      stimulating factor. History of comorbidities and FN events were identified using
      electronic medical records. Cox models adjusting for propensity score, stratified
      by cancer type, were used to determine the association between comorbid
      conditions and FN. Models that additionally adjusted for cancer stage, baseline
      neutrophil count, chemotherapy regimen, and dose reduction were also evaluated.
      RESULTS: A total of 19 160 patients with mean age of 60 years were included; 963
      (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive
      pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart
      failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)],
      autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05
      2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32
      (1.06-1.64)] were all associated with a significantly increased FN risk.
      CONCLUSIONS: These results provide evidence that history of several chronic
      comorbidities increases risk of FN, which should be considered when managing
      patients during chemotherapy.

PMID- 24915872
TI  - Delivery of perioperative chemotherapy for bladder cancer in routine clinical
      practice.
AB  - BACKGROUND: Few articles have documented regimens and timing of perioperative
      chemotherapy for bladder cancer in routine practice. Here, we describe practice
      patterns in the general population of Ontario, Canada. METHODS: In this
      retrospective cohort study, treatment and physician billing records were linked
      to the Ontario Cancer Registry to describe use of neoadjuvant (NACT) and adjuvant
      (ACT) chemotherapy among all patients with muscle-invasive bladder cancer treated
      with cystectomy in Ontario 1994-2008. Time to initiation of ACT (TTAC) was
      measured from cystectomy. Multivariate Cox regression was used to identify
      factors associated with overall (OS) and cancer-specific survival (CSS). RESULTS:
      Of 2944 patients undergoing cystectomy, 4% (129/2944) and 19% (571/2944) were
      treated with NACT and ACT, respectively. Five-year OS was 25% [95% confidence
      interval (CI) 17% to 34%] for NACT, 29% (95% CI 25% to 33%) for ACT cases. Among
      patients with identifiable drug regimens, cisplatin was used in 82% (253/308) and
      carboplatin in 14% (43/308). The most common regimens were gemcitabine-cisplatin
      (54%, 166/308) and methotrexate, vinblastine, doxorubicin, cisplatin (MVAC) (21%,
      66/308). Mean TTAC was 10 weeks; 23% of patients had TTAC >12 weeks. TTAC >12
      weeks was associated with inferior OS [hazard ratio (HR) 1.28, 95% CI 1.00-1.62]
      and CSS (HR 1.30, 95% CI 1.00-1.69). In adjusted analyses, OS and CSS were lower
      among patients treated with carboplatin compared with those treated with
      cisplatin; OS HR 2.14 (95% CI 1.40-3.29) and CSS HR 2.06 (95% CI 1.26-3.37).
      CONCLUSIONS: Most patients in the general population receive cisplatin, and this
      may be associated with superior outcomes to carboplatin. Initiation of ACT beyond
      12 weeks is associated with inferior survival. Patients should start ACT as soon
      as they are medically fit to do so.

PMID- 24915873
TI  - Association between CD8+ T-cell infiltration and breast cancer survival in 12,439
      patients.
AB  - BACKGROUND: T-cell infiltration in estrogen receptor (ER)-negative breast tumours
      has been associated with longer survival. To investigate this association and the
      potential of tumour T-cell infiltration as a prognostic and predictive marker, we
      have conducted the largest study of T cells in breast cancer to date. PATIENTS
      AND METHODS: Four studies totalling 12 439 patients were used for this work.
      Cytotoxic (CD8+) and regulatory (forkhead box protein 3, FOXP3+) T cells were
      quantified using immunohistochemistry (IHC). IHC for CD8 was conducted using
      available material from all four studies (8978 samples) and for FOXP3 from three
      studies (5239 samples)-multiple imputation was used to resolve missing data from
      the remaining patients. Cox regression was used to test for associations with
      breast cancer-specific survival. RESULTS: In ER-negative tumours [triple-negative
      breast cancer and human epidermal growth factor receptor 2 (human epidermal
      growth factor receptor 2 (HER2) positive)], presence of CD8+ T cells within the
      tumour was associated with a 28% [95% confidence interval (CI) 16% to 38%]
      reduction in the hazard of breast cancer-specific mortality, and CD8+ T cells
      within the stroma with a 21% (95% CI 7% to 33%) reduction in hazard. In ER
      positive HER2-positive tumours, CD8+ T cells within the tumour were associated
      with a 27% (95% CI 4% to 44%) reduction in hazard. In ER-negative disease, there
      was evidence for greater benefit from anthracyclines in the National Epirubicin
      Adjuvant Trial in patients with CD8+ tumours [hazard ratio (HR) = 0.54; 95% CI
      0.37-0.79] versus CD8-negative tumours (HR = 0.87; 95% CI 0.55-1.38). The
      difference in effect between these subgroups was significant when limited to
      cases with complete data (P heterogeneity = 0.04) and approached significance in
      imputed data (P heterogeneity = 0.1). CONCLUSIONS: The presence of CD8+ T cells
      in breast cancer is associated with a significant reduction in the relative risk
      of death from disease in both the ER-negative [supplementary Figure S1, available
      at Annals of Oncology online] and the ER-positive HER2-positive subtypes. Tumour
      lymphocytic infiltration may improve risk stratification in breast cancer
      patients classified into these subtypes. NEAT ClinicalTrials.gov: NCT00003577.

PMID- 24915874
TI  - A novel Ehrlichia genotype strain distinguished by the TRP36 gene naturally
      infects cattle in Brazil and causes clinical manifestations associated with
      ehrlichiosis.
AB  - A novel Ehrlichia genotype most closely related to E. canis was reported in North
      American cattle in 2010, and a similar agent was subsequently identified in the
      hemolymph of Brazilian Rhipicephalus (Boophilus) microplus ticks and isolated in
      2012. The purpose of this study was to determine whether this or other novel
      ehrlichial agents naturally infect Brazilian cattle. Using PCR targeting the
      genus-conserved dsb gene, DNA from this novel ehrlichial agent in Brazilian
      cattle was detected. Attempts to isolate the organism in vitro were performed
      using DH82 cells, but morulae and ehrlichial DNA could only be detected for
      approximately one month. In order to further molecularly characterize the
      organism, PCR was performed using primers specific for multiple E. canis genes
      (dsb, rrs, and trp36). Sequence obtained from the conserved rrs and dsb genes
      demonstrated that the organism was 99-100% identical to the novel Ehrlichia
      genotypes previously reported in North American cattle (rrs gene) and Brazilian
      ticks (rrs and dsb genes). However, analysis of the trp36 gene revealed
      substantial strain diversity between these Ehrlichia genotypes strains, including
      divergent tandem repeat sequences. In order to obtain preliminary information on
      the potential pathogenicity of this ehrlichial agent and clinical course of
      infection, a calf was experimentally infected. The calf showed clinical signs of
      ehrlichiosis, including fever, depression, lethargy, thrombocytopenia, and
      morulae were observed in peripheral blood monocytes. This study reports a
      previously unrecognized disease-causing Ehrlichia sp. in Brazilian cattle that is
      consistent with the genotype previously described in North America cattle and
      ticks from Brazil. Hence, it is likely that this is the organism previously
      identified as Ehrlichia bovis in Brazil in 1982. Furthermore, we have concluded
      that strains of these Ehrlichia genotypes can be molecularly distinguished by the
      trp36 gene, which has been widely utilized to define E. canis strain diversity. 

PMID- 24915875
TI  - Diversity and global distribution of the Coxiella intracellular bacterium in
      seabird ticks.
AB  - The obligate intracellular bacterium Coxiella burnetii is the etiological agent
      of Q fever, a widespread zoonotic disease whose most common animal reservoirs are
      domestic ruminants. Recently, a variety of Coxiella-like organisms have also been
      reported from non-mammalian hosts, including pathogenic forms in birds and forms
      without known effects in ticks, raising questions about the potential importance
      of non-mammalian hosts as reservoirs of Coxiella in the wild. In the present
      study, we examined the potential role of globally-distributed seabird ticks as
      reservoirs of these bacteria. To this aim, we tested for Coxiella infection 11
      geographically distinct populations of two tick species frequently found in
      seabird breeding colonies, the hard tick Ixodes uriae (Ixodidae) and soft ticks
      of the Ornithodoros (Carios) capensis group (Argasidae). We found Coxiella-like
      organisms in all O. capensis sensu lato specimens, but only in a few I. uriae
      specimens of one population. The sequencing of 16S rDNA and GroEL gene sequences
      further revealed an unexpected Coxiella diversity, with seven genetically
      distinct Coxiella-like organisms present in seabird tick populations.
      Phylogenetic analyses show that these Coxiella-like organisms originate from
      three divergent subclades within the Coxiella genus and that none of the Coxiella
      strains found in seabird ticks are genetically identical to the forms known to be
      associated with pathogenicity in vertebrates, including C. burnetii. Using this
      data set, we discuss the potential epidemiological significance of the presence
      of Coxiella in seabird ticks. Notably, we suggest that these organisms may not be
      pathogenic forms, but rather behave as endosymbionts engaged in intricate
      interactions with their tick hosts. 

PMID- 24915876
TI  - Synthesis and antiproliferative activity of conjugates of adenosine with muramyl
      dipeptide and nor-muramyl dipeptide derivatives.
AB  - We synthesized a series of MDP(D,D) and nor-MDP(D,D) derivatives conjugated with
      adenosine through a spacer as potential immunosuppressants. New conjugates 8a-k
      were evaluated on two leukemia cell lines (Jurkat and L1210) and PBMC from
      healthy donors. The conjugates 8a-k and MDP(D,D)/nor-MDP(D,D) derivatives 7e, f,
      i, j were active against L1210 cell line. Unconjugated nor-MDP(D,D) had better
      antiproliferative properties, but the conjugates 8b, f, g had the highest values
      of selectivity index. Both cell lines as well as PBMC were resistant to analogs
      11a, b with the 6-aminohexanoic linker. 

PMID- 24915877
TI  - Synthesis and biological activity of fluorescent neonicotinoid insecticide
      thiamethoxam.
AB  - Here, we describe the synthesis of two new fluorescent derivatives of
      thiamethoxam and compared their toxicity on aphid Acyrthosiphon pisum and their
      mode of action on insect nicotinic acetylcholine receptors expressed on the sixth
      abdominal ganglion. The compound 3 with two 2-chlorothiazole moieties was found
      to be more toxic using toxicological bioassays 24 h and 48 h after exposure while
      compound 4 appeared more active using cockroach ganglionic depolarization.
      Interestingly, thiamethoxam appeared more effective than component 3 and 4,
      respectively. Our results demonstrated that component 3 and 4 act as agonists of
      insect nicotinic acetylcholine receptors.

PMID- 24915879
TI  - Triterpenes from Alisma orientalis act as androgen receptor agonists,
      progesterone receptor antagonists, and glucocorticoid receptor antagonists.
AB  - Alisma orientalis, a well-known traditional medicine, exerts numerous
      pharmacological effects including anti-diabetes, anti-hepatitis, and anti
      diuretics but its bioactivity is not fully clear. Androgen receptor (AR),
      progesterone receptor (PR), and glucocorticoid receptor (GR) are three members of
      nuclear receptor superfamily that has been widely targeted for developing
      treatments for essential diseases including prostate cancer and breast cancer. In
      this study, two triterpenes, alisol M 23-acetate and alisol A 23-acetate from
      Alisma orientalis were determined whether they may act as androgen receptor (AR),
      progesterone receptor (PR), or glucocorticoid receptor (GR) modulators. Indeed,
      in the transient transfection reporter assays, alisol M 23-acetate and alisol A
      23-acetate transactivated AR in dose-dependent manner, while they transrepressed
      the transactivation effects exerted by agonist-activated PR and GR. Through
      molecular modeling docking studies, they were shown to respectively interact with
      AR, PR, or GR ligand binding pocket fairly well. All these results indicate that
      alisol M 23-acetate and alisol A 23-acetate from Alisma orientalis might possess
      therapeutic effects through their modulation of AR, PR, and GR pathways. 

PMID- 24915878
TI  - Pentapeptide boronic acid inhibitors of Mycobacterium tuberculosis MycP1
      protease.
AB  - Mycosin protease-1 (MycP1) cleaves ESX secretion-associated protein B (EspB) that
      is a virulence factor of Mycobacterium tuberculosis, and accommodates an
      octapeptide, AVKAASLG, as a short peptide substrate. Because peptidoboronic acids
      are known inhibitors of serine proteases, the synthesis and binding of a boronic
      acid analog of the pentapeptide cleavage product, AVKAA, was studied using MycP1
      variants from Mycobacterium thermoresistible (MycP1mth), Mycobacterium smegmatis
      (MycP1msm) and M. tuberculosis (MycP1mtu). We synthesized the boropentapeptide,
      HAlaValLysAlaAlaB(OH)2 (1) and the analogous pinanediol PD-protected
      HAlaValLysAlaAlaBO2(PD) (2) using an Fmoc/Boc peptide strategy. The pinanediol
      boropentapeptide 2 displayed IC50 values 121.6+/-25.3 MUM for MycP1mth, 93.2+/
      37.3 MUM for MycP1msm and 37.9+/-5.2 MUM for MycP1mtu. Such relatively strong
      binding creates a chance for crystalizing the complex with 2 and finding the
      structure of the unknown MycP1 catalytic site that would potentially facilitate
      the development of new anti-tuberculosis drugs.

PMID- 24915881
TI  - Synthesis, characterization, biological and catalytic applications of transition
      metal complexes derived from Schiff base.
AB  - A novel series of Cu(II), Ni(II), Zn(II), Co(II), and Cd(II) complexes have been
      synthesized from the Schiff base. Structural features were determined by
      analytical and spectral techniques like IR, (1)H NMR, UV-vis, elemental analysis,
      molar electric conductibility, magnetic susceptibility and thermal studies. The
      complexes are found to be soluble in dimethylformamide and dimethylsulfoxide.
      Molar conductance values in dimethylformamide indicate the non-electrolytic
      nature of the complexes. Binding of synthesized complexes with calf thymus DNA
      (CT DNA) was studied. There is significant binding of DNA in lanes 2, 3, and 5.
      Lanes 4 and 6 are showing more florescence when compared to the control
      indicating that these molecules are strongly bound to the DNA by inserting
      themselves between the two stacked base pairs and exhibiting their original
      property of fluorescence. Angiogenesis study has revealed that the compounds B-2,
      B-4 and B-5 have potent antitumor efficacy and activation of antiangiogenesis
      could be one of the possible underlying mechanisms of tumor inhibition. 

PMID- 24915880
TI  - Opioids and efflux transporters. Part 4: influence of N-substitution on P
      glycoprotein substrate activity of noroxymorphone analogues.
AB  - The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the
      central distribution of diverse neurotherapeutics, including opioid analgesics,
      through their active removal from the brain. P-gp located at the blood brain
      barrier has been implicated in the development of tolerance to opioids and
      demonstrated to be up-regulated in rats tolerant to morphine and oxycodone. We
      have previously examined the influence of hydrogen-bonding oxo-substitutents on
      the P-gp-mediated efflux of 4,5-epoxymorphinan analgesics, as well as that of N
      substituted analogues of meperidine. Structure-activity relationships (SAR)
      governing N-substituent effects on opioid efficacy is well-established, however
      the influence of such structural modifications on P-gp-mediated efflux is
      unknown. Here, we present SAR describing P-gp recognition of a short series of N
      modified 4,5-epoxymorphinans. Oxymorphone, naloxone, naltrexone, and nalmexone
      all failed to demonstrate P-gp substrate activity, indicating these opioid
      scaffolds contain structural features that preclude recognition by the
      transporter. These results are examined using mathematical molecular modeling and
      discussed in comparison to other opioid scaffolds bearing similar N-substituents.

PMID- 24915882
TI  - Correlated motions are a fundamental property of beta-sheets.
AB  - Correlated motions in proteins can mediate fundamental biochemical processes such
      as signal transduction and allostery. The mechanisms that underlie these
      processes remain largely unknown due mainly to limitations in their direct
      detection. Here, based on a detailed analysis of protein structures deposited in
      the protein data bank, as well as on state-of-the art molecular simulations, we
      provide general evidence for the transfer of structural information by correlated
      backbone motions, mediated by hydrogen bonds, across beta-sheets. We also show
      that the observed local and long-range correlated motions are mediated by the
      collective motions of beta-sheets and investigate their role in large-scale
      conformational changes. Correlated motions represent a fundamental property of
      beta-sheets that contributes to protein function. 

PMID- 24915883
TI  - Comparison of nanosecond and femtosecond pulsed laser deposition of silver
      nanoparticle films.
AB  - Nanoparticle (NP) films of silver were prepared using nanosecond (ns) and
      femtosecond (fs) pulsed laser deposition (PLD) in vacuum. The flux and energy
      distribution of the ions in the plasma part of the ablation plume were measured
      using a Langmuir ion probe. The deposition energy efficiencies of ns and fs
      silver PLD were also compared. For equivalent thickness up to ~3 nm the NPs made
      by ns-PLD are well separated and roughly circular, but for higher thicknesses the
      NPs begin to coalesce. For equivalent thickness up to 7 nm the fs films are
      comprised of well separated NPs, though the mean NP size and the surface coverage
      increase with equivalent thickness. The mean Feret diameter for both ns- and fs
      PLD films increases with increasing equivalent solid-density thickness. The
      surface plasmon resonance peak was observed to red shift for both ns- and fs-PLD
      films as the equivalent solid-density thickness was increased from 1 nm to 7 nm. 

PMID- 24915884
TI  - Identification and characterization of an operon, msaABCR, that controls
      virulence and biofilm development in Staphylococcus aureus.
AB  - BACKGROUND: Community-acquired, methicillin-resistant Staphylococcus aureus
      strains often cause localized infections in immunocompromised hosts, but some
      strains show enhanced virulence leading to severe infections even among healthy
      individuals with no predisposing risk factors. The genetic basis for this
      enhanced virulence has yet to be determined. S. aureus possesses a wide variety
      of virulence factors, the expression of which is carefully coordinated by a
      variety of regulators. Several virulence regulators have been well characterized,
      but others have yet to be thoroughly investigated. Previously, we identified the
      msa gene as a regulator of several virulence genes, biofilm development, and
      antibiotic resistance. We also found evidence of the involvement of upstream
      genes in msa function. RESULTS: To investigate the mechanism of regulation of the
      msa gene (renamed msaC), we examined the upstream genes whose expression was
      affected by its deletion. We showed that msaC is part of a newly defined four
      gene operon (msaABCR), in which msaC is a non-protein-coding RNA that is
      essential for the function of the operon. Furthermore, we found that an antisense
      RNA (msaR) is complementary to the 5' end of the msaB gene and is expressed in a
      growth phase-dependent manner suggesting that it is involved in regulation of the
      operon. CONCLUSION: These findings allow us to define a new operon that regulates
      fundamental phenotypes in S. aureus such as biofilm development and virulence.
      Characterization of the msaABCR operon will allow us to investigate the mechanism
      of function of this operon and the role of the individual genes in regulation and
      interaction with its targets. This study identifies a new element in the complex
      regulatory circuits in S. aureus, and our findings may be therapeutically
      relevant.

PMID- 24915885
TI  - Neonatal piglet diarrhoea associated with enteroadherent Enterococcus hirae.
AB  - Neonatal porcine diarrhoea of uncertain aetiology is an increasing problem in
      several countries. The aim of the present study was to investigate the unexpected
      finding of enteroadherent cocci in the small intestine of piglets selected for
      necropsy examination from six herds (18 diarrhoeic piglets and 11 healthy
      controls). Gross and microscopical lesions were characterized and selected
      intestinal sections were further examined by immunohistochemistry for expression
      of active caspase-3. The enteroadherent bacterium was characterized in situ by
      Gram staining, ultrastructural imaging, fluorescence in-situ hybridization (FISH)
      and 16S rRNA gene analysis. Species identification of enterococci from intestinal
      cultures was performed by matrix-assisted laser desorption ionization time-of
      flight mass spectrometry (MALDI-TOF MS) for one diarrhoeic and one control animal
      per herd. Gross changes were mild. Microscopically, small intestinal colonization
      by gram-positive cocci was observed in diarrhoeic animals only and was
      accompanied by villus atrophy (4/18) and mild epithelial lesions (10/18),
      including increased apoptosis of enterocytes. Transmission electron microscopy
      revealed coccoid bacteria adjacent to the epithelium, but without effacement of
      microvilli. 16S rRNA gene analysis yielded a sequence identical to Enterococcus
      hirae and FISH identified the enteroadherent bacteria as Enterococcus spp. in all
      colonized animals. The proportion of bacterial isolates identified as E. hirae by
      MALDI-TOF MS analysis was significantly higher (P = 0.0138) in diarrhoeic pigs.
      Species identification was confirmed by species-specific polymerase chain
      reaction for one E. hirae isolate per herd. These isolates were further tested
      for antimicrobial susceptibility, which indicated decreased susceptibility to
      ciprofloxacin for one isolate (minimum inhibitory concentration >4 mg/l). These
      findings suggested that neonatal porcine diarrhoea was associated with small
      intestinal colonization by E. hirae accompanied by mucosal lesions.

PMID- 24915886
TI  - Odontogenic keratocyst in a cat.
AB  - Odontogenic cysts are derived from odontogenic epithelium, can be locally
      invasive and destructive and have been reported rarely in cats. A 16-year-old,
      male domestic shorthair cat had a 3-year history of a slowly progressive, right
      mandibular swelling. Intraoral dental radiographs revealed a multilocular,
      radiolucent, cystic mass within the right mandible that extended from the distal
      aspect of the canine tooth to the mesial aspect of the fourth premolar tooth.
      Radiographically, the mass was associated with distortion and regional
      destruction of the right mandibular bone and resorption of regional tooth roots.
      Histological examination of an incisional biopsy sample revealed multiple
      ruptured cysts lined by stratified squamous epithelium of odontogenic origin with
      luminal parakeratinization and a prominent palisading basal cell layer. The cyst
      contained abundant orthokeratotic and parakeratotic keratin. The clinical,
      radiographical and histological features were consistent with a diagnosis of
      odontogenic keratocyst, as seen in man. This is the first report of an
      odontogenic keratocyst in a cat. 

PMID- 24915887
TI  - Neurolymphomatosis in three horses with multicentric T-cell-rich B-cell lymphoma.
AB  - Neurolymphomatosis is a rare manifestation of lymphoma and is characterized by
      neoplastic infiltration of the peripheral nervous system. The present report
      describes neoplastic infiltration of peripheral nerves in three horses with
      multicentric lymphoma. Immunohistochemistry revealed the presence of CD79a(+)
      lymphoblastic cells and well-differentiated CD3(+) T cells, characteristic of T
      cell-rich B-cell lymphoma in all cases. Nerve infiltration by lymphoma is rare,
      but should be considered as a differential diagnosis for peripheral neuropathy in
      horses with lymphoma.

PMID- 24915888
TI  - Cystic fibrosis related diabetes.
AB  - Improved life expectancy in cystic fibrosis (CF) has led to an expanding
      population of adults with CF, now representing almost 50 % of the total CF
      population. This creates new challenges from long-term complications such as
      diabetes mellitus (DM), a condition that is present in 40 %-50 % of adults with
      CF. Cystic fibrosis-related diabetes (CFRD) results from a primary defect of
      insulin deficiency and although sharing features with type 1 (DM1) and type 2
      diabetes (DM2), it is a clinically distinct condition. Progression to diabetes is
      associated with poorer CF clinical outcomes and increased mortality. CFRD is not
      associated with an increased risk of cardiovascular disease and the prevalence of
      microvascular complications is lower than DM1 or DM2. Rather, the primary goal of
      insulin therapy is the preservation of lung function and optimization of
      nutritional status. There is increasing evidence that appropriate screening and
      early intervention with insulin can reverse weight loss and improve pulmonary
      function. This approach may include targeting postprandial hyperglycemia not
      detected by standard diagnostic tests such as the oral glucose tolerance test.
      Further clinical research is required to guide when and how much to intervene in
      patients who are already dealing with the burden of one chronic illness.

PMID- 24915889
TI  - Autologous islet transplantation in patients requiring pancreatectomy for
      neoplasm.
AB  - Autologous islet cell transplantation is a procedure performed to prevent or
      reduce the severity of diabetes after pancreatic resection. Autologous islet cell
      transplantation is being used almost exclusively in patients undergoing
      pancreatectomy because of painful, chronic pancreatitis, or multiple recurrent
      episodes of pancreatitis that is not controlled by standard medical and surgical
      treatments. Here, we discuss the possibility of extending the clinical
      indications for this treatment on the basis of our experience in patients
      undergoing pancreatic surgery for both nonmalignant and malignant diseases,
      including patients undergoing completion pancreatectomy because of anastomosis
      leakage after pancreaticoduodenectomy and those with pancreatic anastomosis
      deemed at high risk for failure. 

PMID- 24915890
TI  - Effect of continuous positive airway pressure and upper airway surgery on exhaled
      breath condensate and serum biomarkers in patients with sleep apnea.
AB  - INTRODUCTION: Studies on inflammation biomarkers in serum and in exhaled breath
      condensate (EBC) in obstructive sleep apnea (OSA) have shown conflicting results.
      The objective of this study is to assess EBC and serum biomarkers in OSA patients
      at baseline and after continuous positive airway pressure (CPAP) or upper airway
      surgery (UAS). PATIENTS AND METHODS: Nine OSA patients referred for UAS were
      matched for anthropometric characteristics and apnea-hypopnea index with 20
      patients receiving CPAP. pH, nitrite (NO2(-)), nitrate and interleukin 6 in EBC
      and NO2(-), nitrate, leukotriene B4 and interleukin 6 in serum were determined.
      EBC and serum samples were collected at baseline and 3 months after CPAP or UAS.
      RESULTS: Patients' mean body mass index was 30 (range 24.9-40) kg/m(2). EBC
      biomarker levels at baseline were within normal range and did not differ
      significantly after CPAP or UAS. No significant changes were observed in the
      serum concentration of the biomarkers determined after CPAP but the serum
      concentration of NO2(-) increased significantly at 3 months after UAS (P=.0078).
      CONCLUSION: In mildly obese OSA patients, EBC biomarkers of inflammation or
      oxidative stress were normal at baseline and remained unchanged 3 months after
      UAS or CPAP. Although UAS was not effective in terms of reducing OSA severity, it
      was associated with an increase in serum NO2(-).

PMID- 24915891
TI  - Relationship between quantitative cardiac neuronal imaging with 123I-meta
      iodobenzylguanidine and hospitalization in patients with heart failure.
AB  - PURPOSE: Hospitalization in patients with systolic heart failure is associated
      with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged
      by (123)I-meta-iodobenzylguanidine ((123)I-mIBG), has been associated with
      cardiac events in a recent multicenter study. The present analysis explored the
      relationship between (123)I-mIBG imaging findings and hospitalization. METHODS:
      Source documents from the ADMIRE-HF trial were reviewed to identify
      hospitalization events in patients with systolic heart failure following cardiac
      neuronal imaging using (123)I-mIBG. Time to hospitalization was analyzed with the
      Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio
      using multiple-failure Cox regression. RESULTS: During 1.4 years of median follow
      up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom
      had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio
      <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than
      subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for
      elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis,
      a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR
      1.48, 95 % CI 1.05 - 2.0; p = 0.02). CONCLUSION: The mIBG H/M ratio may risk
      stratify patients with heart failure for cardiac-related hospitalization,
      especially when used in conjunction with BNP. Further studies are warranted to
      examine these relationships.

PMID- 24915892
TI  - The evidence base for the use of internal dosimetry in the clinical practice of
      molecular radiotherapy.
AB  - Molecular radiotherapy (MRT) has demonstrated unique therapeutic advantages in
      the treatment of an increasing number of cancers. As with other treatment
      modalities, there is related toxicity to a number of organs at risk. Despite the
      large number of clinical trials over the past several decades, considerable
      uncertainties still remain regarding the optimization of this therapeutic
      approach and one of the vital issues to be answered is whether an absorbed
      radiation dose-response exists that could be used to guide personalized
      treatment. There are only limited and sporadic data investigating MRT dosimetry.
      The determination of dose-effect relationships for MRT has yet to be the explicit
      aim of a clinical trial. The aim of this article was to collate and discuss the
      available evidence for an absorbed radiation dose-effect relationships in MRT
      through a review of published data. Based on a PubMed search, 92 papers were
      found. Out of 79 studies investigating dosimetry, an absorbed dose-effect
      correlation was found in 48. The application of radiobiological modelling to
      clinical data is of increasing importance and the limited published data on
      absorbed dose-effect relationships based on these models are also reviewed. Based
      on National Cancer Institute guideline definition, the studies had a moderate or
      low rate of clinical relevance due to the limited number of studies investigating
      overall survival and absorbed dose. Nevertheless, the evidence strongly implies a
      correlation between the absorbed doses delivered and the response and toxicity,
      indicating that dosimetry-based personalized treatments would improve outcome and
      increase survival. 

PMID- 24915893
TI  - Cardiac neuronal imaging with 123I-meta-iodobenzylguanidine in heart failure:
      implications of endpoint selection and quantitative analysis on clinical
      decisions.

PMID- 24915894
TI  - Neuropeptide S receptor 1 (NPSR1) activates cancer-related pathways and is widely
      expressed in neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) arise from disseminated neuroendocrine cells and
      express general and specific neuroendocrine markers. Neuropeptide S receptor 1
      (NPSR1) is expressed in neuroendocrine cells and its ligand neuropeptide S (NPS)
      affects cell proliferation. Our aim was to study whether NPS/NPSR1 could be used
      as a biomarker for neuroendocrine neoplasms and to identify the gene pathways
      affected by NPS/NPSR1. We collected a cohort of NETs comprised of 91 samples from
      endocrine glands, digestive tract, skin, and lung. Tumor type was validated by
      immunostaining of chromogranin-A and synaptophysin expression and tumor grade was
      analyzed by Ki-67 proliferation index. NPS and NPSR1 expression was quantified by
      immunohistochemistry using polyclonal antibodies against NPS and monoclonal
      antibodies against the amino-terminus and carboxy-terminus of NPSR1 isoform A
      (NPSR1-A). The effects of NPS on downstream signaling were studied in a human SH
      SY5Y neuroblastoma cell line which overexpresses NPSR1-A and is of neuroendocrine
      origin. NPSR1 and NPS were expressed in most NET tissues, with the exception of
      adrenal pheochromocytomas in which NPS/NPSR1 immunoreactivity was very low.
      Transcriptome analysis of NPSR1-A overexpressing cells revealed that mitogen
      activated protein kinase (MAPK) pathways, circadian activity, focal adhesion,
      transforming growth factor beta, and cytokine-cytokine interactions were the most
      altered gene pathways after NPS stimulation. Our results show that NETs are a
      source of NPS and NPSR1, and that NPS affects cancer-related pathways.

PMID- 24915895
TI  - Invasion pattern and histologic features of tumor aggressiveness correlate with
      MMR protein expression, but are independent of activating KRAS and BRAF mutations
      in CRC.
AB  - KRAS/BRAF mutation testing and mismatch repair (MMR) protein immunohistochemistry
      have an established role in routine diagnostic evaluation of colorectal carcinoma
      (CRC). However, since the exact impact of these molecular characteristics on
      tumor morphology and behavior is still subject to research, the aim of our study
      was to examine associations between molecular and morphologic features that had
      not been analyzed in this combination before. KRAS (codons 12, 13, and 61) and
      BRAF (codon 600) mutation status and MMR protein expression were analyzed in a
      consecutive series of 117 CRC samples using DNA pyrosequencing and
      immunohistochemistry. Tumor cell budding, infiltration pattern, and peritumoral
      lymphocytic (PTL) reaction was assessed applying established criteria. Molecular
      and morphological findings were correlated applying chi-square and Fisher's exact
      test. We found KRAS or BRAF mutations in 40 and 8 % of samples, while loss of MMR
      protein expression was observed in 11 %. Tumor budding was significantly
      associated with infiltrative growth, absence of PTLs, and blood and lymph vessel
      infiltration. Neither KRAS nor BRAF mutations were associated with a certain
      growth pattern or budding intensity of CRC, but loss of MMR protein expression
      was found in context with BRAF mutation, expanding growth, and presence of PTLs.
      Our results confirm an association between loss of MMR protein expression,
      presence of activating BRAF mutation, expanding growth, and PTL reaction as well
      as between tumor budding, infiltrative growth pattern, and tumor aggressiveness;
      however, there was no such association between the presence of an activating KRAS
      or BRAF mutation and a distinct invasion pattern or tumor aggressiveness in CRC.

PMID- 24915896
TI  - Monitoring changes in circulating tumour cells as a prognostic indicator of
      overall survival and treatment response in patients with metastatic melanoma.
AB  - BACKGROUND: New effective treatments for metastatic melanoma greatly improve
      survival in a proportion of patients. However biomarkers to identify patients
      that are more likely to benefit from a particular treatment are needed. We
      previously reported on a multimarker approach for the detection of heterogenous
      melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value
      of this multimarker quantification of CTCs and investigated whether changes in
      CTC levels during therapy can be used as a biomarker of treatment response and
      survival outcomes. METHODS: CTCs were captured by targeting the melanoma
      associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5
      and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by
      surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled
      prospectively and CTC counts performed at baseline (prior to treatment), during
      and after treatment. RESULTS: Baseline CTC numbers were not found to be
      prognostic of overall survival nor of progression free survival. However, a low
      baseline CTC number was associated with a rapid response to vemurafenib therapy.
      A decrease in CTCs after treatment initiation was associated with response to
      treatment and prolonged overall survival in vemurafenib treated patients.
      CONCLUSIONS: Measuring changes in CTC numbers during treatment is useful for
      monitoring therapy response in melanoma patients and for providing prognostic
      information relating to overall survival. Further studies with larger sample
      sizes are required to confirm the utility of CTC quantification as a companion
      diagnostic for metastatic melanoma treatment.

PMID- 24915898
TI  - Social organizational stressors and post-disaster mental health disturbances: a
      longitudinal study.
AB  - Social organizational stressors are well-known predictors of mental health
      disturbances (MHD). However, to what extent these stressors predict post-disaster
      MHD among employed victims hardly received scientific attention and is clearly
      understudied. For this purpose we examined to what extent these stressors
      independently predict MHD 1.5 years post-disaster over and above well-known risk
      factors such as disaster exposure, initial MHD and lack of general social
      support, life-events in the past 12 months and demographics (N=423). Exposure,
      social organizational stressors and support were significantly associated with
      almost all examined mental health disturbances on a bi-variate level.
      Multivariate logistic regression analyses showed that these stressors, i.e.
      problems with colleagues, independently predicted anxiety (Adj. OR=5.93),
      depression (Adj. OR=4.21), hostility (Adj. OR=2.85) and having two or more mental
      health disturbances (Adj. OR=3.39) in contrast to disaster exposure. Disaster
      exposure independently predicted symptoms of PTSD symptoms (Adj. OR=2.47) and
      agoraphobia (Adj. OR=2.15) in contrast to social organizational stressors.
      Importantly, levels of disaster exposure were not associated nor correlated with
      (levels of) social organizational stressors. Findings suggest that post-disaster
      mental health care programs aimed at employed affected residents, should target
      social organizational stressors besides disaster-related stressors and lack of
      general social support. 

PMID- 24915897
TI  - Phenotypic plasticity in normal breast derived epithelial cells.
AB  - BACKGROUND: Normal, healthy human breast tissue from a variety of volunteer
      donors has become available for research thanks to the establishment of the Susan
      G. Komen for the Cure(r) Tissue Bank at the IU Simon Cancer Center (KTB).
      Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the
      donated tissue. Explant culture was utilized to isolate the cells from pieces of
      breast tissue. Selective media and trypsinization were employed to select either
      epithelial cells or stromal cells. The primary, non-transformed epithelial cells,
      the focus of this study, were characterized by immunohistochemistry, flow
      cytometry, and in vitro cell culture. RESULTS: All of the primary, non
      transformed epithelial cells tested have the ability to differentiate in vitro
      into a variety of cell types when plated in or on biologic matrices. Cells
      identified include stratified squamous epithelial, osteoclasts, chondrocytes,
      adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The
      cells also express markers of embryonic stem cells. CONCLUSIONS: The cell culture
      conditions employed select an epithelial cell that is pluri/multipotent. The
      plasticity of the epithelial cells developed mimics that seen in metaplastic
      carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and
      may provide clues to the origin of this particularly aggressive type of breast
      cancer. The KTB is a unique biorepository, and the normal breast epithelial cells
      isolated from donated tissue have significant potential as new research tools.

PMID- 24915899
TI  - Safety and efficacy of second-line treatment with folinic acid, 5-fluorouracil
      and irinotecan (FOLFIRI) in combination of panitumumab and bevacizumab for
      patients with metastatic colorectal cancer.
AB  - We investigated the efficacy and safety of a new second-line chemotherapy of
      combining folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with both
      panitumumab and bevacizumab to treat patients with metastatic colorectal cancer
      (mCRC). Patients with mCRC and unsuccessful previous oxaliplatin-based
      chemotherapy were included in the study. The FOLFIRI arm was given FOLFIRI only.
      The FOLFIRI+PB arm was given panitumumab (3 mg/kg) and bevacizumab (3 mg/kg) plus
      FOLFIRI every other week. Between 2009 and 2013, 155 and 137 patients were
      included in the FOLFIRI arm and FOLFIRI+PB arm, respectively. The response rate
      was 40.1 % for FOLFIRI+PB arm versus 30.1 % for FOLFIRI arm. The disease
      controlled rate in FOLFIRI+PB arm was improved to 62.2 from 50.2 % in FOLFIRI
      arm. The median overall survival was 13.9 months in FOLFIRI+PB arm as compared to
      10.7 months in FOLFIRI arm. A series of adverse events were comparable between
      two arms, whereas some of the antibody therapy-associated toxicities were
      observed in FOLFIRI+PB arm. The new strategy of combining panitumumab and
      bevacizumab with FOLFIRI as second-line chemotherapy for patients with mCRC is
      safe and feasible.

PMID- 24915901
TI  - Structural, spectroscopic and functional investigation into Fe-substituted MnSOD
      from human pathogen Clostridium difficile.
AB  - Clostridium difficile, which inhabits the human digestive tract, is an
      etiological agent that causes pseudomembranous colitis and antibiotic-associated
      diarrhea. The oxidative stress tightly relates to its virulence, which highlights
      the function of its superoxide dismutase (SOD). The SOD from Clostridium
      difficile (SODcd) is a Mn/Fe cambialistic SOD with MnSODcd exhibiting an optimal
      activity while Fe-sub-MnSODcd showing 10-fold less activity. To explain why the
      Fe-loaded protein exhibits a much lower activity than the Mn-loaded form, Fe-sub
      MnSODcd and MnSODcd were expressed in E. coli using M9 minimal medium, and
      characterized by X-ray crystallography, metal analysis, optical and EPR pH
      titration, azide binding affinity, etc. The pKa values of the active site
      residues and substrate affinities determined by spectroscopic titrations
      indicated that MnSODcd has a higher affinity for the substrate compared to Fe-sub
      MnSODcd, while Fe-sub-MnSODcd has more affinity for OH(-). The different tendency
      of the anion ligation may be ascribed to the electronic configurations of Fe(3+)
      in d(5)vs. Mn(3+) in d(4), and it could be tuned by the hydrogen-bonding network
      around the active site of SODcd. Furthermore, the free energy for the O2(-)
      oxidation-reduction transition state from DFT calculation demonstrated that
      MnSODcd could disproportionate O2(-) more easily than Fe-sub-MnSODcd. These
      results revealed that SODcd could exquisitely differentiate between the Mn- and
      Fe-based activity. This metal specificity for SODcd may benefit the pathogenicity
      of C. difficile and pave a fundamental way for retarding C. difficile associated
      diseases. 

PMID- 24915900
TI  - Sonic hedgehog signaling may promote invasion and metastasis of oral squamous
      cell carcinoma by activating MMP-9 and E-cadherin expression.
AB  - The aim of this study was to investigate sonic hedgehog (SHH) signaling pathway
      components (Shh and Gli-1), E-cadherin, and MMP-9 expression in human oral
      squamous cell carcinoma (OSCC) and to evaluate their role in prognosis.
      Expression of Shh, Gli-1, and MMP-9 was significantly upregulated in 74 OSCC
      samples compared with non-cancerous tissue samples (Shh IOD: 162.44 +/- 29.35 and
      608.82 +/- 170.99; Gli-1 IOD: 203.50 +/- 71.57 and 831.11 +/- 242.352; MMP-9 IOD:
      196.69 +/- 64.48 and 721.64 +/- 197.99 in non-cancerous and tumor tissues,
      respectively, P < 0.01), whereas E-cadherin expression was downregulated (E
      cadherin IOD: 1,006.19 +/- 230.42 and 442.20 +/- 156.11; in non-cancerous and
      tumor tissues, respectively, P < 0.01). Highly expressed proteins were associated
      with lymph node metastasis; moreover, overexpression of Gli-1 was related to
      tumor recurrence and cancer clinical staging. Spearman's analysis indicated that
      the expression of Gli-1 and MMP-9 was positively correlated, whereas expression
      of Shh/Gli-1 and E-cadherin was negatively correlated. Kaplan-Meier results
      revealed that patients with low Shh, Gli-1, and MMP-9 expression survived longer
      than those with high expression. In contrast, low E-cadherin expression was
      associated with poor prognosis (P < 0.01). In conclusions, transcription factor
      Gli-1 of the SHH signaling pathway may be an important mediator of invasion and
      metastasis of OSCC through induced expression of MMP-9 and E-cadherin and may
      serve as a new prognostic marker.

PMID- 24915902
TI  - Is hemifacial spasm accompanied by hemodynamic changes detectable by ultrasound?
AB  - BACKGROUND: Arterial tortuosity of the posterior circulation compressing the
      facial nerve induces the ephaptic axono-axonal cross-talk that sparks hemifacial
      spasm. We sought if a noninvasive method such as color duplex of these arteries
      might detect hemodynamical changes in this condition. METHODS: Nine patients with
      hemifacial spasm, successfully treated with botulinum toxin, were examined with
      color-coded duplex ultrasound. Mean blood flow velocities of the vertebral,
      basilar, posterior inferior cerebellar, and anterior inferior cerebellar arteries
      were measured and side-to-side comparison performed. RESULTS: In all nine
      patients, the mean blood flow velocity, averaging across the two arteries, was
      higher on the side of the hemifacial spasm (Fisher's exact p < 0.008; two
      tailed). The results of the repeated measures ANOVA show that the main effect of
      side of flow was statistically significant, F(1,8) = 17.354, p = .0032, with
      higher mean blood flow velocities observed on the side of the hemifacial spasm.
      There was no significant association between the mean flow velocity of the
      vertebral artery and the side of spasm (p = 0.523). CONCLUSIONS: Hemifacial spasm
      also seems to relate to hemodynamic changes, which may be detectable by color
      duplex imaging.

PMID- 24915906
TI  - [Focus on the interstitial lung diseases in infancy].

PMID- 24915904
TI  - [Cost effectiveness of a health insurance based case management programme for
      patients with affective disorders].
AB  - OBJECTIVE: Health economic evaluation of a health insurance based case management
      intervention for persons with mood to severe depressive disorders from payers'
      perspective. Intervention intended to raise utilization rates of outpatient
      health services. METHODS: Comparison of patients of one German health insurance
      company in two different regions/states. Cohort study consists of a control
      region offering treatment as usual. Patients in the experimental region were
      exposed to a case management programme guided by health insurance account manager
      who received trainings, quality circles and supervisions prior to intervention.
      Utilization rates of ambulatory psychiatrist and/or psychotherapist should be
      increased. Estimation of incremental cost effectiveness ratio (ICER) was
      intended. RESULTS: Intervention yielded benefits for patients at comparable
      costs. A conservative estimation of the ICER was 44,16 euro. Maximum willingness
      to pay was 378,82 euro per year. Sensitivity analyses showed that this amount of
      maximum willingness to pay can be reduced to 34,34 euro per year or 2,86 euro per
      month due to cost degression effects. CONCLUSIONS: The intervention gains
      increasing cost effectiveness by the number of included patients and case
      managers. Cooperation between health insurances is suggested in order to minimize
      intervention cost and to maximize patient benefits. Results should be confirmed
      by individual longitudinal data (bottom-up approach) first.

PMID- 24915903
TI  - [Social cognition in patients with mood disorders: part I: major depressive
      disorder : a comprehensive review of the literature].
AB  - OBJECTIVE: Overview on the current knowledge regarding social cognition in
      patients with major depressive disorder. METHODS: Selective literature research
      on deficits in social cognition intrinsic to major depressive disorders, their
      occurrence and effects. RESULTS: Deficits in social cognition are considered to
      be core features of major depressive disorder. They are apparent during acute
      episodes of the disorders, endure when patients are in remission and have a
      significant negative impact on the patients' psychosocial outcomes. CONCLUSIONS:
      It is important to consider deficits in social cognition as an integral part of a
      treatment approach to achieve mental stabilization in patients with major
      depressive disorder.

PMID- 24915907
TI  - [Clinical analysis of heterozygous ABCA3 mutations in children].
AB  - OBJECTIVE: To investigate the association of ATP-binding cassette transporter A3
      (ABCA3) gene mutations with severe neonatal respiratory distress syndrome (NRDS)
      and lung disease in children. METHOD: Thirty-eight children hospitalized with
      respiratory disorders in Children's Hospital of Chongqing Medical University from
      January 2010 to December 2011 were screened. Two mutations (E292V, G1221S) in the
      ABCA3 gene were identified. Interstitial lung disease (ILD) was present in 10
      cases, NRDS was found in 23 and congenital pulmonary dysplasia in 5 cases. There
      were 24 males and 14 females, with an age range of 1 hour to 15 years. Genomic
      DNA was prepared from blood samples and sequences were analyzed by polymerase
      chain reaction (PCR). Clinical feature, imaging characteristics and the results
      of gene detection were retrospectively analyzed. RESULT: Four cases with ABCA3
      gene mutations were found; 2 patients (case 2 and case 4) had the heterozygous
      mutation of ABCA3 E292V. One was a 3-hour-old girl and another was a 52-day-old
      boy, 2 patients (case 1 and case 4) had the heterozygous mutation of ABCA3
      G1221S. One was a 78-day-old boy and another was a girl, 15 years and one month
      old. The family history was negative for respiratory disease. Three patients
      (case 1, 2, 4 ) had NRDS and 2 (case 1, 2) of them were premature. One patient
      (case 3) had normal growth and development. She was diagnosed clinically as
      interstitial lung disease (ILD) after admission. The clinical outcomes of 4 cases
      were various. Case 1 had recurrent wheezing and inhaled corticosteroid was
      needed. Case 2 died because she failed to wean from mechanical ventilator. Case 3
      was discharged with improvement but lost to follow-up. Case 4 grows normally.
      CONCLUSION: Genetic variants within ABCA3 may be the genetic causes or background
      of a contributor to some unexplained refractory NRDS, and chronic lung disease
      developed in latter childhood. Identification of ABCA3 genetic variants in NRDS
      infants is important to offer genetic counseling, as well as early prognosis
      estimation and intervention in pediatric chronic lung disease.

PMID- 24915908
TI  - [High resolution computed tomographic findings in infants with diffuse lung
      disease].
AB  - OBJECTIVE: To investigate the high-resolution computed tomographic (HRCT)
      features of infants with diffuse lung disease (DLD) for improving the diagnostic
      accuracy clinically. METHOD: Totally 75 infants under 2 years of age with DLD
      (2010-2013) were involved in this study. Among them, 56 were males and 19
      females, aged from 2 days to 24 months (mean age was 10.9 months). According to
      the clinical or pathological data, the cases were enrolled into three groups,
      including systemic diseases-associated infantile DLD (30 cases), alveolar
      structure disorders-associated infantile DLD (23 cases), and infantile DLD
      specific to infancy (22 cases). Retrospectively, HRCT images, from the three
      groups respectively, were analyzed and compared. HRCT presentations including
      airway disorders, interstitial disorders and air space disorders were reviewed.
      Inter-reviewers consistency check was performed, the consistency between
      reviewers was good (K = 0.64;P = 0.03, < 0.05), as well as chi(2) test. RESULT:
      Among the three groups, some of the HRCT sings (bronchiectasis, thickened
      bronchiolar wall, mosaic sign, reticular, intralobular nodules and
      consolidations) had significant differences (chi(2) = 24.52, 6.08, 18.00, 12.56,
      9.11 and 11.50, P < 0.05) . CONCLUSION: The HRCT features of infantile pulmonary
      DLD/interstitial LD with different causes were as follows, compared to the other
      two groups, intralobular nodules was the main feature of the systemic diseases
      associated infantile DLD, thickened bronchiolar wall, mosaic sign and
      consolidations were rare as well. Meanwhile, bronchiectasis was more common in
      alveolar structural disorders-associated infantile DLD, and reticular opacity was
      rarely seen. Associated clinical data, the HRCT presentations would help
      clinicians to make accurate diagnosis.

PMID- 24915910
TI  - [The diagnosis and treatment of the interstitial lung disease in infants].

PMID- 24915909
TI  - [Effect of bronchoalveolar lavage on the heart rhythm and conduction of the
      children with severe pneumonia].
AB  - OBJECTIVE: To observe the effect of bronchoalveolar lavage on the heart rhythm
      and conduction of children with severe pneumonia through monitoring the
      electrocardiogram change of different step of the bronchoalveolar lavage, for
      proving the safety of the operation of bronchoalveolar lavage from the
      perspective of cardiac electrophysiology. METHOD: From July 2011 to March 2012,
      30 patients who were hospitalized in pneumology department of Dalian Children's
      Hospital and met the inclusion criteria and therapeutic indications of
      bronchoalveolar lavage were chosen. They were 3 to 12 years old, the average age
      was 5.3 years, including 17 boys and 13 girls, the ratio of boys and girls is
      1.3: 1. Continuous sampling the electrocardiogram before and during the process
      including anesthesia, entering into glottis, lavage, aspiration, and revive, and
      recording the heart rate, rhythm amplitude and width of P wave, the PR interval,
      the form and width of QRS complex were also measured. The recorded data were
      analyzed and statistical analysis to reflect the change of the cardiac
      electrophysiology. RESULT: The incidence of heart rate increase was 100.0%, 26
      (86.7%) patients began to emerge after anesthesia, the rest of the patients also
      developed heart rate increase after the start of bronchoscopic operation. All
      patients had sinus tachycardia, and were most obvious in the progress of lavage
      and revive. In the process of entering into glottis, lavage, aspiration, 13
      (43.3%) patients had arrhythmia episodes. Types of arrhythmia included sinus
      bradycardia, atrioventricular block and premature beat. Incidences of
      intraoperative arrhythmia compared with the pre- and post-operation were all
      statistically significantly different (P = 0.00). The most common arrhythmia were
      premature beat, in 17 of the 30 cases there were premature beat including 9 cases
      with atrial premature beats and 8 cases ventricular premature contraction. Two
      patients had III degrees  atrioventricular block accompanied by serious sinus
      bradycardia. All kinds of arrhythmias except sinus tachycardia disappeared after
      the operation was ended. Five patients (16.7%) had PR interval prolongation. Five
      patients (16.7%) had incomplete right bundle branch block (IRBBB) . Incidences of
      IRBBB compared with the pre-operation and post-operation were all not
      significantly different [13.3% (n = 4) vs. 0(n = 0) and 3.3% (n = 1), all P >
      0.05]. Different operating progress made no significant difference in the
      measurement value of electrocardiogram[13.3% (n = 4) vs. 0(n = 0) and 3.3% (n =
      1), all P > 0.05], but showed the most notable effect on heart rate. CONCLUSION:
      Bronchoalveolar lavage can influence the heart rhythm and conduction, but most of
      the influence with pathological significance are transient. Cardiac
      electrophysiological changes were the most obvious in endotracheal operation with
      the risk of malignant arrhythmia but the risk is low, the bronchoalveolar lavage
      technique is safe. The contingency plans for dealing with all kinds of adverse
      reactions must be ready before the operations of bronchoalveolar lavage. During
      the procedure, the patient's ECG changes should be closely monitored to reduce
      the incidence of adverse reactions.

PMID- 24915911
TI  - [Interstitial lung disease in infants caused by genetic abnormalities].

PMID- 24915912
TI  - [Advances in research on the relationship between vitamin D and sleep].

PMID- 24915913
TI  - [Advances in studies on hemophagocytic lymphohistiocytosis].

PMID- 24915914
TI  - [Efficacy and safety of heated humidified high-flow nasal cannula for prevention
      of extubation failure in neonates].
AB  - OBJECTIVE: To assess the efficacy and safety of heated humidified high-flow nasal
      cannula (HHHFNC) ventilation compared with nasal continuous positive airway
      pressure (NCPAP) on prevention of extubation failure in the NICUs. METHOD: A
      prospective randomized, controlled un-blinded study was conducted in 12 tertiary
      hospitals in Hebei Province from December 1, 2012 to May 31, 2013. Neonates were
      eligible for this study if they were admitted to the participating NICUs within 7
      days of postnatal age, and needed noninvasive respiratory support after a period
      of mechanical ventilation with an endotracheal tube. Infants were randomly
      assigned to either HHHFNC or NCPAP group. The primary outcome measures included:
      the incidence of extubation failure, bronchopulmonary dysplasia and the mortality
      before discharge. RESULT: Among the 255 cases included, 128 were in the HHHFNC
      group, and 127 were in the NCPAP group. There was no significant difference in
      gestational age, birth weight, and age at randomization, and male/female ratio
      between the two groups (P > 0.05). There were no significant differences between
      groups for days on ventilation, noninvasive respiratory support, oxygen
      requirement, hospital stay and time to full oral feedings (P > 0.05). The overall
      mortality of the studied population was 10.6% (27/255) . The occurrence of
      extubation failure within 7 days was 9.4% whereas 29.0% in very low birth weight
      infants. There was no significant difference in the extubation failure for HHHFNC
      (12/128, 9.4%) versus NCPAP (12/127, 9.4%) (P > 0.05), or in mortality for HHHFNC
      (12/128, 9.4%) versus NCPAP (15/127, 11.8%) (P > 0.05). No significant difference
      was found between the study groups in the occurrence of bronchopulmonary
      dysplasia (BPD) and most of severe adverse outcomes analyzed, including air leak
      syndrome and nasal trauma. The occurrence of abdominal distention during
      treatment was higher in NCPAP than HHHFNC group (12.6% vs. 5.5%, P < 0.05).
      CONCLUSION: Among infants <= 7 d of postnatal age, HHHFNC appears to have
      efficacy and safety similar to those of NCPAP group when applied immediately post
      extubation to prevent extubation failure. Despite concerns on unmonitored
      pressure delivery during HHHFNC support, no increase of the occurrence of BPD,
      air leak syndrome or mortality was found.

PMID- 24915915
TI  - [Exploring the clinical significance of continuously measuring apparent diffusion
      coefficient values in the preterm infants with punctate white matter damage by
      applying diffusion weighted imaging].
AB  - OBJECTIVE: To observe the dynamic changes of MRI in the preterm infants with
      punctate white matter damage (PWMD), and to explore the clinical significance of
      apparent diffusion coefficient (ADC) values by continuously measuring the lesions
      and surrounding region by applying diffusion weighted imaging (DWI). METHOD: MRI,
      using conventional and diffusion weighted imaging, was performed in 151 preterm
      infants within 7 days after birth between October 2010 to June 2011 in NICU.
      Twenty-four preterm infants with PWMD and 24 controls were obtained according to
      their MRI results. The control group infants were those with normal MRI results
      and at the same gestational age as those with PWMDs. The ADC value was measured
      for the lesions and their surrounding regions, and for the same sites of the
      controls. All the PWMD were followed up for 2-5 weeks, and apparent diffusion
      coefficients were measured at the same regions. The variation of magnetic
      resonance imaging was observed and the apparent diffusion coefficients were
      compared. RESULT: The first MRI scanning: in the 24 cases with PWMD, high signals
      on DWI were seen in all patients (100%), increased signal intensity on T1
      weighted images were seen in 19 (79.2%) patients, increased signal intensity on
      T1-weighted images and decreased signal intensity on T2-weighted images were seen
      in 4 (16.6%) patients. The second MRI scanning: in the 24 cases with PWMD, The
      high signal on DWI vanished in all patients (100%), the increased signal
      intensity on T1-weighted images vanished in 9 (39.1%) patients, the increased
      signal intensity on T1-weighted images did not vanish but was smaller than before
      in 14 (60.9%) patients. The measurement of ADC values: the mean ADC value of the
      lesions in the group of PWMD was (942 +/- 170)*10(-3)mm(2)/s, significantly lower
      than the area surrounding (1 554 +/- 116)*10(-3)mm(2)/s and the same area of the
      control group (1 524 +/- 116)*10(-3)mm(2)/s ( P < 0.05). The second MRI scanning:
      the mean ADC of the lesions in the PWMD group was up to (1 468 +/- 195)*10(
      3)mm(2)/s, which is significantly higher than before, but still lower than the
      areas surrounding the lesion (1 586 +/- 97)*10(-3)mm(2)/s (P < 0.05). CONCLUSION:
      Continuous measurement of ADC values in the lesions and surrounding areas is
      important to describe the micro-change of PWMD.

PMID- 24915916
TI  - [Comparison of the risk factors for asthma in children between urban and rural
      areas in Fuzhou City].
AB  - OBJECTIVE: To explore the prevalence and the different risk factors for asthma in
      children between urban and rural areas in Fuzhou, Fujian province. METHOD: The
      epidemiological survey of asthma in 0-14 years old children was conducted from
      October 2009 to October 2010 between Fuzhou urban and rural areas in Fujian
      province. The investigation subjects were selected in urban and rural areas by
      phased stratified random cluster sampling. The 2010 third national
      epidemiological survey questionnaire of children with asthma was used for
      screening for possible patients. Diagnosis of asthma was confirmed by physical
      examination. The children with asthma were designated as the positive cases,
      while non asthmatic children who were age, gender, ethnic, and living environment
      matched with asthmatic patients were designated as negative control. Comparison
      of the prevalence of asthma in children between Fuzhou urban and rural areas was
      performed. The influencing factors of asthma were analyzed and screened by the
      regression equation model of two element Logistic regression. RESULT: Totally 12
      235 questionnaires of children with asthma and allergic disease screening were
      issued and 11 738 questionnaire were sent back (6 221 were male and 5 517 were
      female). The return rate was 95.9% in urban Fuzhou; 648 children were diagnosed
      as asthma. The prevalence of asthma in male was 6.48% and female children was
      4.44% (comparison of the prevalence of gender chi(2) = 23.267, P < 0.001) in
      urban areas . A total of 6 000 questionnaires of children with asthma and
      allergic disease screening were sent out and 5 860 were responded (male children
      3 228, female children 2 632). The recovery rate was 97.7% in rural Fuzhou; 135
      children with asthma was diagnosed. The prevalence of asthma in male was 2.73%and
      female children and was 1.79%. Adding protein supplement before 6 months (OR =
      1.908, 95%CI:1.233-2.959), the use of antibiotics in the treatment of asthma (OR
      = 14.541, 95%CI:8.920-23.705), furniture materials (non wood) (OR = 2.432,
      95%CI:1.563-3.785) were the main risk factors of children with asthma in urban.
      Adding protein supplement before 6 months(OR = 3.021, 95%CI:1.357-6.711), the use
      of antibiotics in the treatment of asthma(OR = 14.784, 95%CI:3.842-56.885), the
      use of coal as fuel (OR = 63.339, 95% CI: 7.993-501.943), domesticated livestock
      (OR = 13.659, 95% CI:1.342-139.068), the family smoking before and after birth
      (OR = 6.226, 95%CI:2.674-14.495) and chemical fiber pillow (OR = 3.638,
      95%CI:1.241-10.666) were the main risk factors of children with asthma in rural
      areas. CONCLUSION: The prevalence of children with asthma in urban areas was
      higher than that in rural areas. The prevalence of asthma in male children was
      higher than in female children. Adding protein food supplement before 6 months,
      the use of antibiotics and non solid wood furniture material were the main risk
      factors in children with asthma in urban areas. Adding protein supplement before
      6 months, the use of antibiotics, domesticated livestock, the use of coal as fuel
      and the family smoking before and after birth were the main risk factor of asthma
      in children in rural areas.

PMID- 24915917
TI  - [Therapeutic effects of exercise-based treatment programme on children with
      attention-deficit/hyperactivity disorder].
AB  - OBJECTIVE: To evaluate the effects of an exercise-based treatment programme
      (dyslexia, dyspraxia and attention-deficit treatment, DDAT) on various subtypes
      of attention-deficit/hyperactivity disorder (ADHD). METHOD: Ninety-one ADHD
      children with standing balance dysfunction (ADHD-I 43, ADHD-HI 15 and ADHD-C 33)
      were given DDAT for 6 months, the efficacy of DDAT was evaluated before DDAT,
      three, six months after the treatment and three month after end of the treatment
      according to SNAP-IV, before and after the treatment by balancing function test
      and Conners Parents Rating Scale. RESULT: Inattention subscale scores of ADHD-I,
      ADHD-HI and ADHD-C before and after the interventions were 1.99 +/- 0.34, 0.96 +/
      0.31, 2.17 +/- 0.31and 1.19 +/- 0.45, 0.81 +/- 0.28, 1.32 +/- 0.37, differences
      of ADHD-I and ADHD-C were significant (P < 0.05), hyperactivity subscale scores
      of three subtypes of ADHD were 0.81 +/- 0.35, 2.01 +/- 0.35, 1.96 +/- 0.33
      vs.0.45 +/- 0.33, 0.79 +/- 0.41, 1.10 +/- 0.35, there were significant
      differences as well (P < 0.05). The score of hyperactivity symptom was reduced
      more compared to that of inattention symptom by the SNAP-IV scale parent forms.
      There were significant difference before and after the treatment based on Conners
      parent scale for conduct problem (1.11 +/- 0.48 vs. 0.76 +/- 0.44) , learning
      problem (1.97 +/- 0.58 vs.1.60 +/- 0.67), psychosomatic problems (0.61 +/- 0.49
      vs. 0.29 +/- 0.35) , activity/ hyperactivity (1.46 +/- 0.69 vs.1.09 +/- 0.55) and
      anxiousness (1.05 +/- 0.63 vs.0.62 +/- 0.47) as well (P < 0.05); the standing
      balance dysfunction improved for most of the children, total effective rate was
      87.9%, no significant difference was found among the three subtypes (P > 0.05).
      CONCLUSION: DDAT is a safe and efficient intervention for the ADHD children with
      standing balance dysfunction, the improvement on hyperactivity symptom was better
      than that on inattention symptom. This study shows that an exercise-based
      treatment programme for cerebellum function improves symptoms of ADHD and balance
      function.

PMID- 24915918
TI  - [Study on concordance of ictal and interictal epileptiform activity in patients
      with tuberous sclerosis complex].
AB  - OBJECTIVE: To analyze the relationship between the ictal onset zone and dominant
      interictal epileptiform foci in tuberous sclerosis complex (TSC) patients.
      METHOD: Clinical data of 20 patients with TSC which had epileptic seizures during
      Video-EEG monitoring was assessed. Consistency and dominance of focal interictal
      epileptiform activity and the ictal onset zone were identified. Concordance
      between interictal and ictal findings was analyzed. RESULT: Of the 20 patients, 7
      were female, and 13 were male. The age of epilepsy onset was from 15 d to 6
      years. The Video-EEG monitoring age was from 6 months to 11 years. Family history
      was found in three cases. Abnormality in neuroimaging existed in 17 of 18
      patients who were examined. Interictal EEG showed hypsarrhythmia in 3 patients,
      multifocal epileptiform activity with a dominant focus in 12 patients, both focal
      and generalized discharges in 2 patients, and only focal discharges in 3
      patients. The seizures types during EEG monitoring included epileptic spasms,
      partial seizure, atypical absence, and generalized or focal myoclonic seizure.
      The most common seizure type was partial seizure and then epileptic spasms. EEG
      in 4 patients with epileptic spasms showed ictal generalized discharges and
      interictal hypsarrhythmia or generalized discharges. Clinical manifestation of
      epileptic spasms was asymmetric in 3 patients. Lateralization and location of
      interictal and ictal discharges were consistent in 2 of the 3 patients, while
      only lateralization consistency in 1 of the 3 patients. Partial seizures as the
      only seizure type were monitored in 13 patients. Of the 13 patients,
      lateralization and location of interictal and ictal discharges were inconsistent
      in 2 patients (15%), consistent in 8 patients (62%), lateralization or location
      consistent in 2 patients (15%). One case could not be analyzed because of
      uncertainty of lateralization and location of seizure onset. CONCLUSION: In the
      majority of patients with TSC, multifocal interictal epileptiform activity is
      present, in which a most dominance of focal epileptiform activity could be found.
      For some epileptic seizures or the majority of partial seizures, the ictal onset
      zone is concordant with the dominance of focal interictal epileptiform foci. The
      concordance might have positioning reference significance for preoperative
      evaluation of epilepsy surgery.

PMID- 24915919
TI  - [Role of the twenty-four-hour esophageal multichannel intraluminal impedance-pH
      monitoring in preterm infants].
AB  - OBJECTIVE: To evaluate the clinical application of 24-hour esophageal
      multichannel intraluminal impedance-pH monitoring technique in preterm infants.
      METHOD: This study enrolled 28 preterm (male 20, female 8) infants with symptoms
      suggestive of gastroesophageal reflux (GER) (frequent regurgitations, apnea, or
      transcutaneous oxygen saturation decreased). They had postmenstrual age from 26
      to 32 weeks, median (28.9 +/- 1.9)weeks, had birth weight from 850 to 1 700 g,
      median (1 250.4 +/- 272.8)g, range 850-1700 g, and were studied at corrected
      gestational age from 28 to 40 weeks, median (34.5 +/- 2.3)weeks. Combined
      measurement of esophageal pH and impedance was performed. The 24-hour pH
      impedance recording was uploaded onto a portable storage card and for computer
      assisted manual analysis, using a specialized software program. When values were
      distributed normally, they were presented as mean and standard deviation,
      compared using t test. When values were not distributed normally, they were
      presented as median, minimum and maximum. Median values were compared using the
      Mann-Whitney U non-parametric test. SPSS 17.0 software was used. RESULT: In 28
      preterm infants, 71.4% (20/28) had pathological acid refluxes with pH monitor,
      while 100% with combined measurement of esophageal pH and impedance. Gestational
      age, birth weight, corrected gestational age had no association with acid GER.
      Frequent regurgitations, apnea, or transcutaneous oxygen saturation decreased but
      there was no statistically significant difference between acid GER group and non
      acid GER group. Eight cases had no pathological acid refluxes, but showed an
      increase of weakly acid refluxes than pathological acid refluxes group (P < 0.01)
      . The median number of reflux events in 24 hours for 28 cases was 64.5 (0-377) ,
      23.4% were acidic, while 76.4% were weakly acidic; 59.1% were liquid bolus
      refluxes, while 40.9% were mixed bolus refluxes. The positive ratio of symptoms
      related index and symptoms association probability were significantly increased
      combined measurement of esophageal pH and impedance versus pH monitor were used.
      CONCLUSION: The 24-hour esophageal impedance-pH monitoring technique was safe and
      had good tolerance. We confirmed that it detected more weakly acidic refluxes,
      liquid bolus refluxes, and mixed bolus refluxes. And it provided more evidence
      for explaining the relationship between GER and clinical manifestation.

PMID- 24915920
TI  - [NPM1 and CEBPA mutations in pediatric cytogenetically normal acute myeloid
      leukemia].
AB  - OBJECTIVE: To evaluate the frequency of the nucleophosmin (NPM1) gene and the
      CCAAT/enhancer binding protein alpha gene (CEBPA) through polymerase chain
      reaction (PCR) array in pediatric patients with cytogenetically normal acute
      myeloid leukemia (CN-AML) and explore the clinical significances of these
      mutations. METHOD: Between August 2009 and December 2012, 30 children (<16 years
      old) with newly diagnosed CN-AML were included. The clinical characteristics were
      analyzed in these patients. PCR combined with direct sequencing was used to
      detect NPM1, CEBPA gene mutations. All the data were statistically analyzed using
      SPSS17.0 software. RESULT: The gene mutations were detected in each of the 30
      patients. NPM1 mutation was positive in three patients (10%) with type A
      mutation, while CEBPA mutation was positive in two patients (6.7%) with double
      mutations (TAD, bZIP) . Besides, FLT3/ITD mutation was positive in three
      patients. Patients with NPM1 or FLT3/ITD had a significantly elevated diagnostic
      WBC count with a median diagnostic WBC count of 102.80*10(9)/L compared with
      18.56*10(9)/L for the patients without mutations(t = 2.353, P = 0.043), as well
      as the marrow blast percentage (94.0% vs. 80.0%, t = 3.804, P = 0.002). The
      complete remission was achieved in all the 3 patients with NPM1 mutations and 2
      patients with CEBPA mutations. All the patients with these mutations also
      achieved 2-year event-free survival (EFS) and 2-year overall survival (OS), while
      2-year EFS and 2-year OS of the other patients were (40.1 +/- 11.2)% and (51.8 +/
      10.9)% (P = 0.044, 0.091, respectively). CONCLUSION: NPM1 and CEBPA mutations
      may indicate a favorable prognosis in pediatric CN-AML.

PMID- 24915921
TI  - [Adverse effects of type B ventricular pre-excitation on ventricular wall motion
      and left ventricular function: clinical analysis of 9 cases].
AB  - OBJECTIVE: To analyze the adverse effects of type B ventricular pre-excitation on
      ventricular wall motion and left ventricular function and its clinical
      characteristic. METHOD: The clinical, electrophysiological and echocardiographic
      characteristics of the 9 cases with type B ventricular pre-excitation before and
      after ablation seen between March 2011 and March 2013 were analyzed. The patients
      aged from 3 to 16 years. Five of them were female. RESULT: Dyschronous left
      ventricular contraction was demonstrated by M-Mode echocardiography in all of the
      cases. The basal segments of the interventricular septum turned thin and moved in
      a manner similar to that of an aneurysm, with typical bulging during end-systole,
      which was observed in six cases. All patients received successful RFCAs. The
      locations of the accessory pathways (APs) were the right-sided anteroseptum (n =
      2) and the free wall (n = 7). Their physical activities and growth improved
      greatly in the four cases with coexisting dilated cardiomyopathy (DCM). The
      echocardiographic data demonstrated that their LV contraction recovered to
      synchrony shortly after the ablation, LVEF recovered to normal and LVED decreased
      to almost normal gradually during the follow-up. CONCLUSION: Overt right-sided
      APs may have adverse effects on ventricular wall motion and left ventricular
      function. They can even result in DCM. Dyssynchronous ventricular contraction
      induced by right-sided overt accessory pathway may be the vital mechanism. Such
      kinds of cases are indication for ablation with good prognosis.

PMID- 24915922
TI  - [Clinical and molecular characteristics of a child with juvenile Sandhoff
      disease].
AB  - OBJECTIVE: To explore the clinical features and molecular mutation of HEXB gene
      in a case with juvenile Sandhoff disease. METHOD: We retrospectively reviewed the
      clinical, neuroimaging and biochemical findings in this Chinese child with
      juvenile Sandhoff disease. Hexosaminidase A and hexosaminidase A & B activities
      were measured in blood leukocytes by fluorometric assay. HEXB gene molecular
      analysis was performed by PCR and direct sequencing. RESULT: The 9-year-old boy
      was admitted for psychomotor regression. He presented slowly progressive gait
      disorder and dysarthria during the last three years. Cranial MRI revealed a
      marked cerebellar atrophy with normal intensity in the thalamus and basal
      ganglia. Brain MRS showed normal in the thalamus and basal ganglia.
      Hexosaminidase A was 69.5 (mg.h) [normal controls 150-360 nmol/(mg.h)],
      hexosaminidase A & B activity was 119 nmol/(mg.h)[normal controls 600-3 500
      nmol/(mg.h)], confirming the diagnosis of Sandhoff disease. The patient was a
      compound heterozygote for a novel deletion mutation c.1404delT (p. P468P fsX62)
      and a reported mutation c.1509-26G>A. CONCLUSION: The clinical features of
      juvenile Sandhoff disease include ataxia, dysarthria and cerebellar atrophy. The
      enzyme assay and molecular analysis of HEXB gene can confirm the diagnosis of
      Sandhoff disease. The novel mutation c.1404delT(p. P468P fsX62) is a disease
      related mutation.

PMID- 24915923
TI  - [A case of neuroendocrine cell hyperplasia of infancy (NEHI)].

PMID- 24915924
TI  - [Summary of 2013 annual academic conference on neonatology].

PMID- 24915926
TI  - Detection and characterization of avastrovirus associated with diarrhea isolated
      from minks in China.
AB  - Astroviruses are becoming a growing concern in veterinary and public health. Many
      astrovirus species are associated with enteric diseases have been described in
      both mammalian and avian hosts. In the present study, 23 fecal samples from
      diarrheic minks were collected in Liaoning and Shandong Province, and an
      investigation of astrovirus was performed using biochemical methods and RT-PCR
      assay with specific primers. A total of four mink astroviral isolates were
      detected from sick minks with diarrhea problems. Further sequencing and
      characterization of the partial ORF1b gene and ORF2 gene segments revealed low
      sequence identities (20.0-85.3 and 31.8-87.2%) with known astroviral strains,
      indicating the emergence of a novel clade of astroviruses. Some new features of
      the astroviral genome have also been discovered. The phylogenetic tree revealed
      that all samples were distantly related to mink astrovirus and were closely
      related to chicken astroviruses and turkey astroviruses. MK/DL-1, MK/DL-2, MK/SD
      1, and MK/SD-2 formed a new clade and were found to be more closely related to
      astroviruses from birds than to other mink strains, indicating past cross-species
      transmission and considerable zoonotic potential.

PMID- 24915927
TI  - Identifying the unmet health needs of patients with congenital hypogonadotropic
      hypogonadism using a web-based needs assessment: implications for online
      interventions and peer-to-peer support.
AB  - BACKGROUND: Patients with rare diseases such as congenital hypogonadotropic
      hypogonadism (CHH) are dispersed, often challenged to find specialized care and
      face other health disparities. The internet has the potential to reach a wide
      audience of rare disease patients and can help connect patients and specialists.
      Therefore, this study aimed to: (i) determine if web-based platforms could be
      effectively used to conduct an online needs assessment of dispersed CHH patients;
      (ii) identify the unmet health and informational needs of CHH patients and (iii)
      assess patient acceptability regarding patient-centered, web-based interventions
      to bridge shortfalls in care. METHODS: A sequential mixed-methods design was
      used: first, an online survey was conducted to evaluate health promoting behavior
      and identify unmet health and informational needs of CHH men. Subsequently,
      patient focus groups were held to explore specific patient-identified targets for
      care and to examine the acceptability of possible online interventions.
      Descriptive statistics and thematic qualitative analyses were used. RESULTS: 105
      male participants completed the online survey (mean age 37 +/- 11, range 19-66
      years) representing a spectrum of patients across a broad socioeconomic range and
      all but one subject had adequate healthcare literacy. The survey revealed periods
      of non-adherence to treatment (34/93, 37%) and gaps in healthcare (36/87, 41%)
      exceeding one year. Patient focus groups identified lasting psychological effects
      related to feelings of isolation, shame and body-image concerns. Survey
      respondents were active internet users, nearly all had sought CHH information
      online (101/105, 96%), and they rated the internet, healthcare providers, and
      online community as equally important CHH information sources. Focus group
      participants were overwhelmingly positive regarding online interventions/support
      with links to reach expert healthcare providers and for peer-to-peer support.
      CONCLUSION: The web-based needs assessment was an effective way to reach
      dispersed CHH patients. These individuals often have long gaps in care and
      struggle with the psychosocial sequelae of CHH. They are highly motivated
      internet users seeking information and tapping into online communities and are
      receptive to novel web-based interventions addressing their unmet needs.

PMID- 24915928
TI  - Improvements in social and adaptive functioning following short-duration PRT
      program: a clinical replication.
AB  - Pivotal Response Treatment (PRT) is an empirically validated behavioral treatment
      for individuals with autism spectrum disorders (ASD). The purpose of the current
      study was to assess the efficacy of PRT for ten cognitively-able preschool-aged
      children with ASD in the context of a short-duration (4-month) treatment model.
      Most research on PRT used individual behavioral goals as outcome measures, but
      the current study utilized standardized assessments of broader-based social
      communication and adaptive skills. The children made substantial gains; however,
      magnitude and consistency of response across measures were variable. The results
      provide additional support for the efficacy of PRT as well as evidence for
      improvements in higher-order social communication and adaptive skill development
      within the context of a short-duration PRT model. 

PMID- 24915929
TI  - Quantifying narrative ability in autism spectrum disorder: a computational
      linguistic analysis of narrative coherence.
AB  - Autism is a neurodevelopmental disorder characterized by serious difficulties
      with the social use of language, along with impaired social functioning and
      ritualistic/repetitive behaviors (American Psychiatric Association in Diagnostic
      and statistical manual of mental disorders: DSM-5, 5th edn. American Psychiatric
      Association, Arlington, 2013). While substantial heterogeneity exists in symptom
      expression, impairments in language discourse skills, including narrative (or
      storytelling), are universally observed in autism (Tager-Flusberg et al. in
      Handbook on autism and pervasive developmental disorders, 3rd edn. Wiley, New
      York, pp 335-364, 2005). This study applied a computational linguistic tool,
      Latent Semantic Analysis (LSA), to objectively characterize narrative performance
      in high-functioning individuals with autism and typically-developing controls,
      across two different narrative contexts that differ in the interpersonal and
      cognitive demands placed on the narrator. Results indicated that high-functioning
      individuals with autism produced narratives comparable in semantic content to
      those produced by controls when narrating from a picture book, but produced
      narratives diminished in semantic quality in a more demanding narrative recall
      task. This pattern is similar to that detected from analyses of hand-coded
      picture book narratives in prior research, and extends findings to an additional
      narrative context that proves particularly challenging for individuals with
      autism. Results are discussed in terms of the utility of LSA as a quantitative,
      objective, and efficient measure of narrative ability. 

PMID- 24915931
TI  - Brief report: trends in US National autism awareness from 2004 to 2014: the
      impact of national autism awareness month.
AB  - We sought to evaluate the potential for using historical web search data on
      autism spectrum disorders (ASD)-related topics as an indicator of ASD awareness.
      Analysis of Google Trend data suggested that National Autism Awareness Month and
      televised reports concerning autism are an effective method of promoting online
      search interest in autism. 

PMID- 24915930
TI  - Adult outcomes in autism: community inclusion and living skills.
AB  - Longitudinal research has demonstrated that social outcomes for adults with
      autism are restricted, particularly in terms of employment and living
      arrangements. However, understanding of individual and environmental factors that
      influence these outcomes is far from complete. This longitudinal study followed a
      community sample of children and adolescents with autism into adulthood. Social
      outcomes in relation to community inclusion and living skills were examined,
      including the predictive role of a range of individual factors and the
      environment (socio-economic disadvantage). Overall, the degree of community
      inclusion and living skills was restricted for the majority, and while childhood
      IQ was an important determinant of these outcomes, it was not the sole predictor.
      The implications of these findings in relation to interventions are discussed. 

PMID- 24915932
TI  - Experiences of receiving a diagnosis of autism spectrum disorder: a survey of
      adults in the United kingdom.
AB  - A total of 128 adults with high-functioning autism spectrum disorders were
      surveyed concerning the process they went through to obtain their diagnosis and
      the subsequent support they received. Results suggested that routes to diagnosis
      were quite heterogeneous and overall levels of satisfaction with the diagnostic
      process were mixed; 40 % of respondents were 'very/quite' dissatisfied, whilst 47
      % were 'very/quite' satisfied. The extent of delays, number of professionals
      seen, quality of information given at diagnosis and levels of post-diagnostic
      support predicted overall satisfaction with the diagnostic process. Important
      areas and suggestions for improvement were noted for all stages of the diagnostic
      pathway. Respondents also displayed above average levels of depressed mood and
      anxiety, with greater support being requested in this area. 

PMID- 24915933
TI  - Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well
      as Nrf2 and NF-kB pathway inhibition.
AB  - BACKGROUND: Disulfiram (DS), an anti-alcoholism drug, demonstrates strong
      antitumor activity in a copper (Cu)-dependent manner. This study investigates the
      cytotoxicity of DS/Cu complex in lymphoid malignant cell lines in vitro and in
      vivo. METHOD: Raji cells were subjected to different treatments and thereafter
      MTT assay, flow cytometry were used to determine IC50 and apoptotic status. We
      also tested the cytotoxicity of DS/Cu in acute lymphoblastic leukemia cell line
      Molt4 in vitro. In vivo experiments were also performed to demonstrate the
      anticancer efficacy of DS/Cu in Raji cells xenografted nude mice. RESULTS: In
      combination with a low concentration (1 MUM) of Cu2+, DS induced cytotoxicity in
      Raji cells with an IC50 of 0.085 +/- 0.015 MUM and in Molt4 cells with an IC50 of
      0.435 +/- 0.109 MUM. The results of our animal experiments also showed that the
      mean tumor volume in DS/Cu-treated mice was significantly smaller than that in DS
      or control group, indicating that DS/Cu inhibits the proliferation of Raji cells
      in vivo. DS/Cu also induced apoptosis in 2 lymphoid malignant cell lines. After
      exposure to DS (3.3 MUM)/Cu (1 MUM) for 24 hours, apoptosis was detected in 81.03
      +/- 7.91% of Raji cells. DS/Cu induced significant apoptosis in a concentration
      dependent manner with the highest apoptotic proportion (DS/Cu: 89.867 +/- 4.69%)
      at a concentration of 2 MUM in Molt4 cells. After 24 h exposure, DS/Cu inhibits
      Nrf2 expression. Flow cytometric analysis shows that DS/Cu induced ROS
      generation. DS/Cu induced phosphorylation of JNK and inhibits p65 expression as
      well as Nrf2 expression both in vitro and in vivo. N-acetyl-L-cysteine (NAC), an
      antioxidant, can partially attenuate DS/Cu complex-induced apoptosis and block
      JNK activation in vitro. In addition, NAC is able to restore Nrf2 nuclear
      translocation and p65 expression. CONCLUSION: Our study manifests that DS/Cu
      complex targets lymphoid malignant cells in vitro and in vivo. Generation of ROS
      might be one of core steps in DS/Cu induced apoptosis. Moreover, ROS-related
      activation of JNK pathway and inhibition of NF-kappaB and Nrf2 may also
      contribute to the DS/Cu induced apoptosis.

PMID- 24915934
TI  - GRP receptor imaging of prostate cancer using [(99m)Tc]Demobesin 4: a first-in
      man study.
AB  - PURPOSE: We explored the imaging of bombesin receptors and evaluated the clinical
      use of [(99m)Tc]Demobesin 4 ([(99m)Tc]DB4) in prostate cancer patients.
      PROCEDURES: [(99m)Tc]DB4 was prepared according to Good Manufacturing Practice.
      Patients with prostate cancer underwent serial planar and SPECT imaging up to 3 h
      after administration. Blood and urine samples were taken to assess
      pharmacokinetics. RESULTS: [(99m)Tc]DB4 is safe and clears rapidly from the
      bloodstream via the kidneys resulting in low background activity. The tracer
      binds strongly to the gastrin-releasing peptide receptor (GRPR) in vivo as
      indicated by the high uptake in the pancreas seen in all patients. In patients
      who had undergone hormone therapy, [(99m)Tc]DB4 did not efficiently image
      metastatic prostate cancer. In contrast, in newly diagnosed patients local
      disease was visualised. CONCLUSIONS: The GRPR is an unsuitable target for imaging
      refractory prostate cancer but may be useful in untreated disease. [(99m)Tc]DB4
      is a promising radiopharmaceutical which merits further exploration in this
      specific group of patients.

PMID- 24915935
TI  - Dose-dependent uptake of 3'-deoxy-3'-[(18) F]fluorothymidine by the bowel after
      total-body irradiation.
AB  - PURPOSE: The aim of this study is to non-invasively assess early, irradiation
      induced normal tissue alterations via metabolic imaging with 3'-deoxy-3'-[(18)
      F]fluorothymidine ([(18) F]FLT). PROCEDURES: Twenty-nine male C57BL/6 mice were
      investigated by [(18) F]FLT positron emission tomography for 7 days after total
      body irradiation (1, 4, and 8 Gy) versus 'sham' irradiation (0 Gy).
      Target/background ratios were determined. The imaging results were validated by
      histology and immunohistochemistry (Thymidine kinase 1, Ki-67). RESULTS: [(18)
      F]FLT demonstrated a dose-dependent intestinal accumulation post irradiation.
      Mean target/background ratio (+/-standard error) 0 Gy: 1.4 (0.2), 1 Gy: 1.7
      (0.1), 4 Gy: 3.1 (0.3), 8 Gy: 4.2 (0.6). Receiver operating characteristic
      analysis (area under the curve, p value): 0 vs. 1 Gy: 0.81, 0.049; 0 vs. 4 Gy:
      1.0, 0.0016; and 0 vs. 8 Gy: 1.0, 0.0020. Immunohistochemistry confirmed the
      results. CONCLUSIONS: [(18) F]FLT seems to provide dose-dependent information on
      radiation-induced proliferation in the bowel. This opens the perspective for
      monitoring therapy-related side-effects as well as assessing, e.g., radiation
      accident victims.

PMID- 24915936
TI  - Successful percutaneous treatment for massive hemorrhage due to infectious
      pseudoaneurysm in the abdominal wall after percutaneous endoscopic gastrostomy: a
      case report.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is often performed for
      alimentation and to prevent weight loss in patients with feeding problems due to
      central neurologic diseases such as cerebral infarction or intracranial
      hemorrhage. Although infection at the skin site after PEG placement is a typical
      late complication of PEG, a ruptured infectious pseudoaneurysm caused massive
      bleeding adjacent to the tract is rare. Prompt treatment is required to avoid the
      hemorrhage shock, however surgical ligation is difficult to obtain the arrest of
      bleeding in damaged skin due to the infection. CASE PRESENTATION: A 70-year-old
      male was bedridden due a cerebral infarction suffered 1 year previously. APEG was
      placed because of feeding problems, and a push-type, 20-Fr gastrostomy tube was
      inserted through the anterior abdominal wall. On day 16 after PEG placement, the
      patient had massive bleeding from the PEG site due to the rupture of infectious
      pseudoaneurysm and developed a decreased level of consciousness and hypotension.
      Treatment by percutaneous direct injection of a mixture of n-butyl-cyanoacrylate
      (NBCA)-lipiodol was performed and achieved good hemostasis is obtained.
      CONCLUSIONS: A rare case of an infectious pseudoaneurysm that developed in the
      abdominal wall and caused massive bleeding at a PEG placement site was described.
      Percutaneous injection of a mixture of n-butyl-cyanoacrylate (NBCA)-lipiodol
      under ultrasound guidance is an effective treatment in this case.

PMID- 24915937
TI  - Internal threshold of toxicological concern values: enabling route-to-route
      extrapolation.
AB  - The TTC concept uses toxicological data from animal testing to derive generic
      human exposure threshold values (TTC values), below which the risk of adverse
      effects on human health is considered to be low. It uses distributions of no
      observed-adverse-effect levels (NOAELs) for substances. The 5th percentile value
      is divided by an uncertainty factor (100) to give a TTC value. As the
      toxicological data underpinning the TTC concept are from tests with oral
      exposure, the exposure is to be understood as an external oral exposure. For risk
      assessment of substances with a low absorption (by the oral route, or through
      skin), the internal exposure is more relevant than the external exposure.
      European legislation allows that tests might not be necessary for substances with
      negligible absorption with low internal exposure. The aim of this work is to
      derive internal TTC values to allow the TTC concept to be applied to situations
      of low internal exposure. The external NOAEL of each chemical of three databases
      (Munro, ELINCS, Food Contact Materials) was multiplied by the bioavailability of
      the individual chemical. Oral bioavailability was predicted using an in silico
      prediction tool (ACD Percepta). After applying a reduced uncertainty factor of
      25, we derived internal TTC values. For Cramer class I, the internal TTC values
      are 6.9 MUg/kg bw/d (90 % confidence interval: 3.8-11.5 mg/kg bw/d); for Cramer
      class II/III 0.1 MUg/kg bw/d (90 % confidence interval: 0.08-0.14 MUg/kg bw/d).

PMID- 24915938
TI  - In vivo toxicity, metabolism and pharmacokinetic properties of FAK inhibitor 14
      or Y15 (1, 2, 4, 5-benzenetetramine tetrahydrochloride).
AB  - Y15 or inhibitor 14 (1,2,4,5-benzenetetramine tetrahydrochloride) is a potent and
      specific inhibitor of focal adhesion kinase that inhibits its autophosphorylation
      activity, decreases the viability of cancer cells, and blocks tumor growth. In
      this preclinical study, we analyzed the pharmacokinetics of Y15 in mice plasma,
      its metabolic stability in mouse and human liver microsomes and toxicity in mice.
      The pharmacokinetics study in mice demonstrated that, following intraperitoneal
      administration at 30 mg/kg dose, Y15 was very rapidly absorbed in mice, reaching
      maximum plasma concentration in 4.8 min. Y15 rapidly metabolized in mouse and
      human liver microsomes with half-life t1/2 of 6.9 and 11.6 min, respectively. The
      maximal tolerated dose of single-dose administration of Y15 by oral
      administration was 200 mg/kg, and the multiple maximum tolerated dose of Y15 was
      100 mg/kg by PO during 7 day study. Y15 did not cause any mortality or
      statistically significant differences in the body weight at 30 mg/kg by IP during
      28-day study, and at 100 mg/kg by PO during the 7-day study. There were no
      clinical chemical, hematological, or histopathological changes in different mice
      organs at 30 mg/kg by IP during 28 days and at 100 mg/kg dose by PO during 7
      days. Thus, this is the first preclinical toxicity, pharmacokinetics, and
      metabolic stability study of Y15 inhibitor. Further development of Y15 will
      provide a basis for new therapeutic and future clinical studies. 

PMID- 24915939
TI  - Epidemiology and microbiological investigations of community-acquired pneumonia
      in children admitted at the emergency department of a university hospital.
AB  - BACKGROUND: The management of children with community-acquired pneumonia (CAP) is
      largely influenced by the development of new molecular diagnostic tests that
      allow the simultaneous detection of a wide range of pathogens. OBJECTIVES:
      Evaluation of a diagnostic approach including multiplex PCR assays for revisiting
      the epidemiology and etiology of CAP in children at hospital. STUDY DESIGN:
      Children of all ages consulting at the Emergency Department of the University
      hospital of Saint-Etienne, France, during the 2012-2013 winter period were
      included. In addition to bacterial cultures, the following pathogens were
      detected using biplex commercially-available rt-PCR tests: adenovirus,
      respiratory syncytial virus, human metapneumovirus, bocavirus,
      rhinovirus/enterovirus, coronavirus, influenza viruses A and B, parainfluenza
      viruses, Mycoplasma pneumoniae and Chlamydophila pneumonia. RESULTS: From 85
      patients with CAP, at least one pathogen was identified in 81 cases (95.3%),
      including 4 bacterial exclusive infections (4.7%), 53 viral exclusive infections
      (62.4%) and 24 mixed infections (28.2%). Coinfection by at least two viruses was
      observed in 37 cases (43.5%). Mean age was higher in the case of documented
      bacterial infection (P<0.05). In the subgroup of viral exclusive infection, the
      mean age of severe cases was 2.0 years vs 3.8 years in mild and moderate cases
      (P<0.05). CONCLUSIONS: These findings highlight the huge proportion of CAP of
      viral origin, the high number of co-infection by multiple viruses and the low
      number of bacterial CAP, notably in children under 5 years, and address the need
      to re-evaluate the indications of empiric antimicrobial treatment in this age
      group.

PMID- 24915940
TI  - Ultrasonographic evaluation of anal endometriosis: report of four cases.
AB  - BACKGROUND: The presence of endometriosis in the anal canal and perianal tissues
      is rare and difficult to suspect at clinical examination. We report our
      experience with preoperative ultrasound evaluation of four cases of anal
      endometriosis. METHODS: Four patients were evaluated by transperineal and high
      resolution three-dimensional endoanal ultrasonography. RESULTS: In 3 of 4 women,
      the lesions involved old episiotomy scars. Anal endometriosis appeared as
      hypoechoic cystic lesions with areas of microcalcification, not well delimited
      and highly vascularized. The lesions either involved the anal sphincter (n = 2,
      one within the rectovaginal septum) or were localized superficially in the
      ischiorectal space (n = 2). Surgery and pathologic exam confirmed the
      ultrasonographic findings. CONCLUSIONS: Ultrasonographic findings of anal
      endometriosis are characteristics and may allow accurate preoperative staging of
      the disease.

PMID- 24915941
TI  - Comparison of the effectiveness of infliximab and adalimumab in preventing
      postoperative recurrence in patients with Crohn's disease: an open-label, pilot
      study.
AB  - BACKGROUND: Endoscopic and clinical recurrence of Crohn's disease (CD) appears in
      up to 80 and 30 % of patients, respectively, 1 year after surgery. Both
      infliximab (IFX) and adalimumab (ADA) have been demonstrated to be effective in
      reducing the possibility of recurrence after surgery, but head-to-head studies
      have not been performed so far. The aim of this open-label prospective study was
      to compare endoscopic, histological and clinical recurrence after 1 year of
      treatment with IFX or ADA as postoperative prophylaxis in CD patients with a high
      risk of recurrence. METHODS: Consecutive CD patients who underwent curative
      ileocolonic resection were randomized to receive IFX or ADA for 1 year. Co
      primary endpoints were endoscopic, histological and clinical recurrence after 12
      months of therapy. RESULTS: Twenty consecutive CD patients (9 males and 11
      females; median age 32.5 years, range 20-39 years) were enrolled after undergoing
      curative ileocolonic resection. Among the 10 patients treated with IFX, 2 (20 %)
      had endoscopic recurrence compared to 1 (10 %) in the group of 10 ADA patients (p
      = 1.0). Three out of 10 (30 %) IFX patients and 2 out of 10 (20 %) ADA patients
      had histological recurrence (p = 1.0). No significant clinical differences were
      found between the two groups. CONCLUSIONS: IFX and ADA were similar in preventing
      histological, endoscopic and clinical recurrence after curative ileocolonic
      resection in high risk CD patients.

PMID- 24915942
TI  - Radiofrequency ablation for chronic radiation proctitis: our initial experience
      with four cases.
AB  - BACKGROUND: Chronic radiation proctitis (CRP) occurs up to 20 % of patients after
      pelvic radiotherapy, with rectal bleeding as the main presenting complaint.
      Radiofrequency ablation (RFA) has recently been used in the management of
      Barrett's esophagus, but its efficacy in CRP has to be studied. The aim of this
      case series was to describe four cases of patients with CRP treated with RFA that
      demonstrate the efficacy and safety of the technique. METHODS: All the procedures
      were performed with HALO 90 or HALO 90 Ultra ablation catheter fitted on the
      distal end of a standard flexible endoscope. For each patient, the severity of
      symptoms was assessed at baseline and after the last treatment session. RESULTS:
      At least two sessions of RFA (maximum 4) were necessary, at three-month
      intervals, to completely control the symptoms. No major complications were
      observed. CONCLUSIONS: RFA was effective and safe for control bleeding in this
      case series. Adequately powered randomized controlled trials are needed to
      establish the safety and efficacy of RFA for CRP.

PMID- 24915943
TI  - 'There are a lot of new people in town: but they are here for soccer, not for
      business' a qualitative inquiry into the impact of the 2010 soccer world cup on
      sex work in South Africa.
AB  - BACKGROUND: Sports mega-events have expanded in size, popularity and cost.
      Fuelled by media speculation and moral panics, myths proliferate about the
      increase in trafficking into forced prostitution as well as sex work in the run
      up to such events. This qualitative enquiry explores the perceptions of male,
      female and transgender sex workers of the 2010 Soccer World Cup held in South
      Africa, and the impact it had on their work and private lives. METHODS: A multi
      method study design was employed. Data consisted of 14 Focus Group Discussions,
      53 sex worker diaries, and responses to two questions in surveys with 1059 male,
      female and transgender sex workers in three cities. RESULTS: Overall, a minority
      of participants noted changes to the sex sector due to the World Cup and nothing
      emerged on the feared increases in trafficking into forced prostitution.
      Participants who observed changes in their work mainly described differences,
      both positive and negative, in working conditions, income and client relations,
      as well as police harassment. The accounts of changes were heterogeneous - often
      conflicting in the same research site and across sites. CONCLUSIONS: No major
      shifts occurred in sex work during the World Cup, and only a few inconsequential
      changes were noted. Sports mega-events provide strategic opportunities to expand
      health and human rights programmes to sex workers. The 2010 World Cup missed that
      opportunity.

PMID- 24915945
TI  - Role of NF-kappaB-dependent signaling and p38 MAPK signaling pathway in the
      control of hemopoiesis during cytostatic administration.
AB  - The study examines the role of signal pathways in triggering the compensatory
      reactions in the blood system in response to the cytostatic administration. In
      vitro experiments elucidated the involvement of protein kinase p38 in the
      synthesis of granulocytic CSF by cells of hemopoietic microenvironment. The
      important role of the transcriptional factor NF-kappaB and protein kinase p38 in
      limitation of the processes of maturation of the hemopoietic precursors was
      demonstrated. 

PMID- 24915944
TI  - A tale of tails: deciphering the contribution of terminal tails to the
      biochemical properties of two Dps proteins from Streptomyces coelicolor.
AB  - Dps proteins are members of an extensive family of proteins that oxidise and
      deposit iron in the form of ferric oxide, and are also able to bind DNA.
      Ferroxidation centres are formed at the interface of anti-parallel dimers, which
      further assemble into dodecameric nanocages with a hollow core where ferric oxide
      is deposited. Streptomyces coelicolor encodes three Dps-like proteins (DpsA, B
      and C). Despite sharing the conserved four-helix bundle organisation observed in
      members of the Dps family, they display significant differences in the length of
      terminal extensions, or tails. DpsA possess both N- and C-terminal tails of
      different lengths, and their removal affects quaternary structure assembly to
      varying degrees. DpsC quaternary structure, on the other hand, is heavily
      dependent on its N-terminal tail as its removal abolishes correct protein
      folding. Analysis of the crystal structure of dodecamers from both proteins
      revealed remarkable differences in the position of tails and interface surface
      area; and provides insight to explain the differences in biochemical behaviour
      observed while comparing DpsA and DpsC.

PMID- 24915946
TI  - Experimental study of the efficiency of Dietressa preparation on body weight
      reduction in mice feeding high-fat ration.
AB  - We studied the efficiency of Dietressa on body weight reduction in C57Bl/6 male
      mice feeding standard high-fat ration (24%). After 5-month daily intragastric
      administration of Dietressa, body weight gain was the lowest in comparison with
      other groups and did not differ from that in mice receiving the reference
      substance sibutramine for 5 months. In contrast to sibutramine, Dietressa did not
      increase motor activity of animals in the open field test and produced no
      anorectic effect. The mean body weight gain per each 1000 kcal of consumed food
      in the group of animals receiving Dietressa was lower than in the control group
      and mice receiving sibutramine. 

PMID- 24915947
TI  - Distribution of antigen-presenting cells CD68 in papillomavirus infection in the
      skin.
AB  - We analyzed local reactions of immune homeostasis in the human skin, in
      particular, effector immune cells CD68 responsible for antigen presentation,
      during human papillomavirus infection. Under conditions of long-term
      papillomavirus infection, CD68 markers were identifi ed only in the connective
      tissue of the skin (derma) and were completely absent in the epidermis, where
      they were found during physiological and reparative regeneration after thermal
      injury. We concluded that hypertrophy of the epidermis and connective tissue of
      the dermal papillary layer in human papillomavirus infection is related to the
      absence of CD68 immune cells in the epithelial plate and their accumulation in
      the connective tissue adjacent to the basement membrane of the epidermis. The
      possibility of epithelium contamination with the virus depends on local immune
      homeostasis. Therefore, induction of proper CD68 distribution in appropriate
      structures can contribute to normalization of epithelial-connective tissue
      interactions. 

PMID- 24915948
TI  - Experimental osteoporosis and its correction.
AB  - Osteoporosis was modeled in rats by chronic (6 months) treatment with omeprazole
      or serotonin, and bone tissue status was studied in experimental hepatic fibrosis
      and during serotonin treatment under conditions of hepatic fibrosis. Serum levels
      of calcium, phosphorus, alkaline phosphatase, albumins, and creatinine and bone
      tissue levels of calcium, phosphorus, magnesium, and iron were measured.
      Treatment with mesenchymal stem cells over 6 months reduced the severity of
      osteoporosis. 

PMID- 24915949
TI  - Expression of insulin-like growth factors in the placenta in preeclampsia.
AB  - Comparative morphological study of the placentas in women with preeclampsia and
      small-for-date fetuses was carried out. Expression of insulin-like growth factor
      1 (IGF-1), insulin-like growth factor-2 (IGF-2), and insulin-like growth factor
      binding protein-3 (IGFBP-3) was detected by immunohistochemical methods. Low
      expression of IGF-1 and high expression of IGF-2 and IGFBP-3 in the placental
      tissue depending on preeclampsia severity were detected. The most pronounced
      changes were found in preeclampsia associated with small-for-date fetuses.

PMID- 24915950
TI  - Effects of a local focus of granulation tissue formed in the bone marrow cavity
      on reparative osteogenesis.
AB  - The stimulatory effect of a local focus of granulation tissue, created in the
      bone marrow cavity, on reparative osteogenesis after tibial bone fracture was
      detected in experimental rats by microscopic examination of histological
      sections, scanning electron microscopy, and X-ray electron probe microanalysis. 

PMID- 24915951
TI  - A method for evaluation of membrane permeability for water by the erythrocyte
      osmotic deformability profiles.
AB  - We developed a method for evaluation of membrane permeability for water based on
      the analysis of osmotic permeability profiles of red blood cells. Deformability
      of completely spherulated erythrocytes changed in a dose-dependent manner during
      formation of artificial water pores (by nystatin) and blocking (by HgCl2) of the
      existing ones. 

PMID- 24915952
TI  - Poly(epsilon-caprolactone) nerve conduit and local delivery of vegf and fgf2
      genes stimulate neuroregeneration.
AB  - We studied regeneration of rat sciatic nerve while overcoming of a 5-mm diastasis
      with the aid of nanostructured conduit made of biocompatible and biodegradable
      poly(epsilon-caprolactone) and filled with fibrin hydrogel matrix. Implantation
      of the conduit into the nerve in combination with local delivery of the
      expression plasmid carrying genes encoding vascular endothelial growth factor
      (vegf) and fibroblast growth factor 2 (fgf2) leads to an increase in number of
      myelinated fibers and S-100(+) cells in the peripheral nerve stump and improved
      recovery of the nerve function. Under conditions of direct gene therapy, an
      advantage of electrospun poly(epsilon-caprolactone) conduit with high-porosity
      was revealed on the basis of these criteria in comparison with biocompatible
      silicon conduit. 

PMID- 24915954
TI  - The bioinspired construction of an ordered carbon nitride array for
      photocatalytic mediated enzymatic reduction.
AB  - A carbon nitride array (CNA) material has been constructed using a sacrificial
      diatom template. A regular carbon nitride nanorod array could be replicated from
      the periodic and regular nanochannel array of the template. The directional
      charge transport properties and high light harvesting capability of the CNA gives
      much better performance in splitting water to give hydrogen than its bulk
      counterpart. Furthermore, by combining with a rhodium complex as a mediator, the
      nicotinamide adenine dinucleotide (NADH) cofactor of many enzymes could be
      photocatalytically regenerated by the CNA. The rate of the in situ NADH
      regeneration is high enough to reverse the biological pathway of the three
      dehydrogenase enzymes, which then leads to the sustainable conversion of
      formaldehyde to methanol and also the reduction of carbon dioxide into methanol. 

PMID- 24915956
TI  - Amygdalohippocampectomy for epilepsy in a patient with prior ipsilateral deep
      brain stimulator lead placement.
AB  - In light of failed medical therapy for movement disorders, the use of deep brain
      stimulation (DBS) has increased the last two decades. Many complications may
      transpire; however, to our knowledge, the literature does not mention the
      phenomena of brain shift from a second unrelated neurosurgical procedure and its
      theoretical effect on lead displacement and lead function. We present a patient
      with a left sided DBS for essential tremor and subsequent left
      amygdalohippocampectomy for temporal lobe epilepsy with minimal radiographic
      distortion of the DBS lead and without clinical or functional complications. A 47
      year-old woman presented with bitemporal epilepsy secondary to a brain injury
      acquired in childhood in addition to a comorbid bilateral essential tremor, both
      refractory to medical intervention. A successful left-sided DBS placement was
      performed with satisfactory resolution of her essential tremor. The patient
      subsequently developed deterioration of seizure control, becoming refractory to
      anti-epileptic medications, requiring surgical intervention. A left-sided
      selective amygdalohippocampectomy and techniques to minimize brain shift were
      performed without complications. Postoperative imaging suggested minimal
      distortion of the DBS lead. This did not correspond with reemergence of her
      essential tremor, implying that the lead maintained functional utility. Brain
      shift secondary to a craniotomy may cause DBS lead displacement. This phenomenon
      should be considered when planning operative approaches and can be limited by
      selective resections. With the growing propensity for placement of DBS leads and
      the risk of lead displacement, it is important to consider operative approaches
      to minimize brain shift. 

PMID- 24915955
TI  - Hotline update of clinical trials and registries presented at the American
      College of Cardiology Congress 2014.
AB  - This article provides information and commentaries on trials which were presented
      at the Hotline and Clinical Trial Update Sessions during the Late Breaking
      Clinical Trial Sessions at the 63rd annual meeting of the American College of
      Cardiology in Washington, USA, from 29th to 31st March 2014. This article gives
      an overview on a number of novel clinical trials in the field of cardiovascular
      medicine, which were presented. Comprehensive summaries have been generated from
      the oral presentation and the webcasts of the American College of Cardiology,
      similar to as previously reported and should provide the readers with the most
      comprehensive information of relevant publications. The discussed studies are US
      CoreValve, Choice, Symplcity-HTN-3, GRS, ZEUS, GIPS-III, HEAT-PPCI, COPR-2, MSC
      HF, POISE-2, SIRS. The data were presented by leading experts in the field. 

PMID- 24915957
TI  - Factors predicting incremental administration of antihypertensive boluses during
      deep brain stimulator placement for Parkinson's disease.
AB  - Hypertension is common in deep brain stimulator (DBS) placement predisposing to
      intracranial hemorrhage. This retrospective review evaluates factors predicting
      incremental antihypertensive use intraoperatively. Medical records of Parkinson's
      disease (PD) patients undergoing DBS procedure between 2008-2011 were reviewed
      after Institutional Review Board approval. Anesthesia medication, preoperative
      levodopa dose, age, preoperative use of antihypertensive medications, diabetes
      mellitus, anxiety, motor part of the Unified Parkinson's Disease Rating Scale
      score and PD duration were collected. Univariate and multivariate analysis was
      done between each patient characteristic and the number of antihypertensive
      boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on
      angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers
      (ARB), told to hold on the morning of surgery. Antihypertensive medications were
      given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95%
      confidence interval [CI] 1.00-1.02; p=0.005), high Joint National Committee (JNC)
      class (p<0.0001), diabetes mellitus (RR 1.4; 95%CI 1.2-17; p<0.0001) and duration
      of PD >10 years (RR 1.2; 95%CI 1.1-1.3; p=0.001) were independent predictors for
      antihypertensive use. No difference was noted in the mean dose of levodopa
      (p=0.1) and levodopa equivalent dose (p=0.4) between the low (I/II) and high
      severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not
      influence antihypertensive boluses required (p=0.38). Intraoperative hypertension
      during DBS surgery is associated with higher age group, hypertensive, diabetic
      patients and longer duration of PD. Withholding ACEI or ARB is an independent
      predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal
      and choice of anesthetic agent is not associated with higher intraoperative
      antihypertensive medications.

PMID- 24915958
TI  - Transcervical migration of a broken dental needle: a case report and literature
      review.
AB  - Although needle breakage is a rare event in dentistry, the occurrence can cause
      significant distress to the patient and the clinician. Taking appropriate
      measures to prevent this mishap is best. However, when this event occurs,
      appropriate planning and retrieval of the needle can lessen the detrimental
      effects. In this report, we document the migration and retrieval of a broken
      dental needle that traveled from the medial ramus of the mandible to the
      posterior cervical space. This report emphasizes the importance of proper local
      anesthesia techniques, as well as preventive measures, localization methods, and
      the principles of surgical approaches for the removal of broken needles. 

PMID- 24915959
TI  - Polarization-dependent SERS effects of laser-generated sub-100 nm antenna
      structures.
AB  - Sub-100 nm antenna arrays consisting of a star-like ridge or dome-like structures
      with needles in their centers are prepared in thin gold films on glass substrates
      using femtosecond laser pulses. The needles can be bent mechanically to be
      horizontally aligned to the substrate surface. Controlled variation of the pulse
      energy allows one to obtain nanostructures of different defined morphologies.
      These arrays of nanostructures are covered with a thin homogeneous layer of
      rhodamine molecules. Raman spectra using linearly polarized laser light of 632.8
      nm are taken with the laser spot centered on individual nanostructures and at
      positions on the unstructured film. The average Raman enhancement within the
      laser spot focused onto a nanostructure is two orders of magnitude higher than on
      the unstructured film. The nanostructures with bent needles exhibit a
      polarization dependence of the SERS effect, i.e., typically the enhancement is
      larger by about a factor of two for excitation light polarized parallel to the
      needle direction than for the perpendicular case. The enhancement factor of the
      star-like ridge structures with needles is analyzed by the finite-element method,
      which agrees with the experiment. We show that the variation of the SERS activity
      of almost similar structures arises from the inherent randomness of the hot spots
      created in the fabrication process. Nevertheless, these antenna structures may be
      useful as elements in novel SERS devices as they can be accurately positioned on
      a device using a cheap fabrication process compatible with microfabrication
      technology. 

PMID- 24915960
TI  - The expression of apoptosis inducing factor (AIF) is associated with aging
      related cell death in the cortex but not in the hippocampus in the TgCRND8 mouse
      model of Alzheimer's disease.
AB  - BACKGROUND: Recent evidence has suggested that Alzheimer's disease (AD)
      associated neuronal loss may occur via the caspase-independent route of
      programmed cell death (PCD) in addition to caspase-dependent mechanisms. However,
      the brain region specificity of caspase-independent PCD in AD-associated
      neurodegeneration is unknown. We therefore used the transgenic CRND8 (TgCRND8) AD
      mouse model to explore whether the apoptosis inducing factor (AIF), a key
      mediator of caspase-independent PCD, contributes to cell loss in selected brain
      regions in the course of aging. RESULTS: Increased expression of truncated AIF
      (tAIF), which is directly responsible for cell death induction, was observed at
      both 4- and 6-months of age in the cortex. Concomitant with the up-regulation of
      tAIF was an increase in the nuclear translocation of this protein. Heightened
      tAIF expression or translocation was not observed in the hippocampus or
      cerebellum, which were used as AD-vulnerable and relatively AD-spared regions,
      respectively. The cortical alterations in tAIF levels were accompanied by
      increased Bax expression and mitochondrial translocation. This effect was
      preceded by a significant reduction in ATP content and an increase in reactive
      oxygen species (ROS) production, detectable at 2 months of age despite negligible
      amounts of amyloid-beta peptides (Abeta). CONCLUSIONS: Taken together, these data
      suggest that AIF is likely to play a region-specific role in AD-related caspase
      independent PCD, which is consistent with aging-associated mitochondrial
      impairment and oxidative stress.

PMID- 24915961
TI  - Pre-eclampsia: an update.
AB  - Pre-eclampsia remains the second leading direct cause of maternal death, >99 % of
      which occurs in less developed countries. Over 90 percent of the observed
      reduction in pre-eclampsia-related maternal deaths in the UK (1952-2008) occurred
      with antenatal surveillance and timed delivery. In this review, we discuss the
      pathogenesis, diagnostic criteria, disease prediction models, prevention and
      management of pre-eclampsia. The Pre-eclampsia Integrated Estimate of RiSk
      (PIERS) models and markers of angiogenic imbalance identify women at incremental
      risk for severe pre-eclampsia complications. For women at high risk of developing
      pre-eclampsia, low doses of aspirin (especially if started <17 weeks) and calcium
      are evidence-based preventative strategies; heparin is less so. Severe
      hypertension must be treated and the Control of Hypertension In Pregnancy (CHIPS)
      Trial (reporting: 2014) will guide non-severe hypertension management. Magnesium
      sulfate prevents and treats eclampsia; there is insufficient evidence to support
      alternative regimens. Pre-eclampsia predicts later cardiovascular disease;
      however, at this time we do not know what to do about it.

PMID- 24915962
TI  - Qualitative observation instrument to measure the quality of parent-child
      interactions in young children with type 1 diabetes mellitus.
AB  - BACKGROUND: In young children with type 1 diabetes mellitus (T1DM), parents have
      complete responsibility for the diabetes-management. In toddlers and
      (pre)schoolers, the tasks needed to achieve optimal blood glucose control may
      interfere with normal developmental processes and could negatively affect the
      quality of parent-child interaction. Several observational instruments are
      available to measure the quality of the parent-child interaction. However, no
      observational instrument for diabetes-specific situations is available.
      Therefore, the aim of the present study was to develop a qualitative observation
      instrument, to be able to assess parent-child interaction during diabetes
      specific situations. METHODS: First, in a pilot study (n = 15), the observation
      instrument was developed in four steps: (a) defining relevant diabetes-specific
      situations; (b) videotaping these situations; (c) describing all behaviors in a
      qualitative observation instrument; (d) evaluating usability and reliability.
      Next, we examined preliminary validity (total n = 77) by testing hypotheses about
      correlations between the observation instrument for diabetes-specific situations,
      a generic observation instrument and a behavioral questionnaire. RESULTS: The
      observation instrument to assess parent-child interaction during diabetes
      specific situations, which consists of ten domains: "emotional involvement",
      "limit setting", "respect for autonomy", "quality of instruction", "negative
      behavior", "avoidance", "cooperative behavior", "child's response to injection",
      "emphasis on diabetes", and "mealtime structure", was developed for use during a
      mealtime situation (including glucose monitoring and insulin administration).
      CONCLUSIONS: The present study showed encouraging indications for the usability
      and inter-rater reliability (weighted kappa was 0.73) of the qualitative
      observation instrument. Furthermore, promising indications for the preliminary
      validity of the observation instrument for diabetes-specific situations were
      found (r ranged between |.24| and |.45| for significant correlations and between
      |.10| and |.23| for non-significant trends). This observation instrument could be
      used in future research to (a) test whether parent-child interactions are
      associated with outcomes (like HbA1c levels and psychosocial functioning), and
      (b) evaluate interventions, aimed at optimizing the quality of parent-child
      interactions in families with a young child with T1DM.

PMID- 24915963
TI  - Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug
      induced liver injury models.
AB  - INTRODUCTION: Mesenchymal stem cell-conditioned medium (MSC-CM) has been shown to
      have protective effects against various cellular-injury models. This mechanism of
      protection, however, has yet to be elucidated. Recently, exosomes were identified
      as the active component in MSC-CM. The aim of this study is to investigate the
      effect of MSC-derived exosomes in an established carbon tetrachloride (CCl4)
      induced liver injury mouse model. This potential effect is then validated by
      using in vitro xenobiotic-induced liver-injury assays: (1) acetaminophen (APAP)-
      and (2) hydrogen peroxide (H2O2)-induced liver injury. METHODS: The exosomes were
      introduced concurrent with CCl4 into a mouse model through different routes of
      administration. Biochemical analysis was performed based on the blood and liver
      tissues. Subsequently the exosomes were treated in APAP and H2O2-toxicants with
      in vitro models. Cell viability was measured, and biomarkers indicative of
      regenerative and oxidative biochemical responses were determined to probe the
      mechanism of any hepatoprotective activity observed. RESULTS: In contrast to mice
      treated with phosphate-buffered saline, CCl4 injury in mice was attenuated by
      concurrent-treatment exosomes, and characterized by an increase in hepatocyte
      proliferation, as demonstrated with proliferating cell nuclear antigen (PCNA)
      elevation. Significantly higher cell viability was demonstrated in the exosomes
      treated group compared with the non-exosome-treated group in both injury models.
      The higher survival rate was associated with upregulation of the priming-phase
      genes during liver regeneration, which subsequently led to higher expression of
      proliferation proteins (PCNA and cyclin D1) in the exosomes-treated group.
      Exosomes also inhibited the APAP- and H2O2-induced hepatocytes apoptosis through
      upregulation of Bcl-xL protein expression. However, exosomes do not mitigate
      hepatocyte injury via modulation of oxidative stress. CONCLUSIONS: In summary,
      these results suggest that MSC-derived exosomes can elicit hepatoprotective
      effects against toxicants-induced injury, mainly through activation of
      proliferative and regenerative responses.

PMID- 24915965
TI  - Forests fuel fish growth in freshwater deltas.
AB  - Aquatic ecosystems are fuelled by biogeochemical inputs from surrounding lands
      and within-lake primary production. Disturbances that change these inputs may
      affect how aquatic ecosystems function and deliver services vital to humans. Here
      we test, using a forest cover gradient across eight separate catchments, whether
      disturbances that remove terrestrial biomass lower organic matter inputs into
      freshwater lakes, thereby reducing food web productivity. We focus on deltas
      formed at the stream-lake interface where terrestrial-derived particulate
      material is deposited. We find that organic matter export increases from more
      forested catchments, enhancing bacterial biomass. This transfers energy upwards
      through communities of heavier zooplankton, leading to a fourfold increase in
      weights of planktivorous young-of-the-year fish. At least 34% of fish biomass is
      supported by terrestrial primary production, increasing to 66% with greater
      forest cover. Habitat tracers confirm fish were closely associated with
      individual catchments, demonstrating that watershed protection and restoration
      increase biomass in critical life-stages of fish. 

PMID- 24915966
TI  - Effects of oxytocin used during delivery on development: a retrospective cohort
      study.
AB  - OBJECTIVE: The objective was to evaluate the potential influence of oxytocin
      administered during delivery on children's development at the age of 5. METHOD:
      This study was designed as a retrospective cohort study where children from
      patients given synthetic oxytocin during delivery were considered as the exposed
      cohort and children from patients not given oxytocin as the nonexposed cohort.
      From a total of 7465 births attended at our maternity ward in 2006, an initial
      sample of 400 was randomly selected. A total of 148 children were evaluated using
      the Battelle Developmental Inventory. Potential confounding and adjustment
      factors were analyzed using stratified analysis and multivariate analysis
      (logistic regression). RESULTS: Oxytocin use did not significantly affect the
      overall risk of developmental delay in the study sample (relative risk, RR, 1.46;
      95% confidence interval, CI [0.79-2.71]). The best fit regression model included
      twin delivery, type of delivery, and maternal age. In the group of vaginal
      noninstrumental deliveries, oxytocin administration increased the risk of poor
      Battelle Developmental Inventory outcome, particularly when maternal age was
      under 28 or over 35 years of age (odds ratio, OR, 67.14; 95% CI [5.46-824.86]).
      When delivery was instrumental or through cesarean section in mothers aged 28-35
      years, oxytocin administration decreased the risk of developmental disorders (OR
      0.16; 95% CI [0.04-0.66]). CONCLUSION: Although oxytocin administration during
      delivery did not affect the overall risk of low Battelle Developmental Inventory
      scores in the study sample, some effects were seen according to maternal age and
      type of birth.

PMID- 24915964
TI  - The role of the right temporoparietal junction in attention and social
      interaction as revealed by ALE meta-analysis.
AB  - The right temporoparietal junction (rTPJ) is frequently associated with different
      capacities that to shift attention to unexpected stimuli (reorienting of
      attention) and to understand others' (false) mental state [theory of mind (ToM),
      typically represented by false belief tasks]. Competing hypotheses either suggest
      the rTPJ representing a unitary region involved in separate cognitive functions
      or consisting of subregions subserving distinct processes. We conducted
      activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A
      conjunction analysis across ALE meta-analyses delineating regions consistently
      recruited by reorienting of attention and false belief studies revealed the
      anterior rTPJ, suggesting an overarching role of this specific region. Moreover,
      the anatomical difference analysis unravelled the posterior rTPJ as higher
      converging in false belief compared with reorienting of attention tasks. This
      supports the concept of an exclusive role of the posterior rTPJ in the social
      domain. These results were complemented by meta-analytic connectivity mapping
      (MACM) and resting-state functional connectivity (RSFC) analysis to investigate
      whole-brain connectivity patterns in task-constrained and task-free brain states.
      This allowed for detailing the functional separation of the anterior and
      posterior rTPJ. The combination of MACM and RSFC mapping showed that the
      posterior rTPJ has connectivity patterns with typical ToM regions, whereas the
      anterior part of rTPJ co-activates with the attentional network. Taken together,
      our data suggest that rTPJ contains two functionally fractionated subregions:
      while posterior rTPJ seems exclusively involved in the social domain, anterior
      rTPJ is involved in both, attention and ToM, conceivably indicating an
      attentional shifting role of this region.

PMID- 24915967
TI  - Activation of Dopamine D1 Receptors Regulates Dendritic Morphogenesis Through
      Rac1 and RhoA in Prefrontal Cortex Neurons.
AB  - Dopamine (DA) is an important regulator of neuronal plasticity in the prefrontal
      cortex (PFC) and plays a critical role in addiction-related neuroadaptation. The
      Rho GTPases, including Rac1, RhoA and Cdc42, are key regulators of actin
      cytoskeleton rearrangement that play important roles in dendritic morphogenesis.
      The goal of the current study was to use cultures of primary PFC neurons to gain
      a better understanding of the molecular mechanisms underlying DA-induced
      dendritic morphogenesis, a phenomenon that mimics the increase in DA synaptic
      transmission observed in the PFC of in vivo cocaine administration. We
      investigated the effects of repeated DA treatments on dendritic morphology
      changes in PFC neurons, and identified Rac1 and RhoA as downstream effectors of
      D1 receptors during the regulation of dendritic morphogenesis. Importantly, we
      found that D1 receptor-regulated Rac1 and RhoA have distinct roles in the
      regulation of dendritic morphogenesis after repeated DA treatments. Our data
      provide the first evidence that Rac1 and RhoA are effectors of D1 receptor
      signaling during dendritic morphogenesis and represent new signaling molecules
      involved in long-lasting neuroadaptation in the PFC. 

PMID- 24915968
TI  - Electroacupuncture attenuates cerebral ischemia-reperfusion injury in diabetic
      mice through adiponectin receptor 1-mediated phosphorylation of GSK-3beta.
AB  - Diabetes mellitus substantially increases the risk of stroke and enhances brain's
      vulnerability to ischemia insult. Electroacupuncture (EA) pretreatment was proved
      to induce cerebral ischemic tolerance in normal stroke models. Whether EA could
      attenuate cerebral ischemia injury in diabetic mice and the possible underlying
      mechanism are still unrevealed. Male C57BL/6 mice were subjected to
      streptozotocin (STZ) for diabetic models. After inducing focal cerebral ischemia
      model, the levels of plasma and cerebral adiponectin (APN) were measured as well
      as the expression of cerebral adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2).
      The neurobehavioral score, infarction volume, and cellular apoptosis were
      evaluated with or without AdipoR1 short interfering RNA (siRNA). The role of
      phosphorylation of glycogen synthesis kinase 3 beta (GSK-3beta) at Ser-9 in the
      EA pretreatment was also assessed. EA pretreatment increased both plasma and
      cerebral APN levels and enhanced neuronal AdipoR1 in diabetic mice. In addition,
      EA reduced infarct size, improved neurological outcomes, and inhibited cell
      apoptosis after reperfusion. These beneficial effects were reversed by AdipoR1
      knockdown. Furthermore, EA increased GSK-3beta phosphorylation (p-GSK-3beta) in
      the ipsilateral penumbra. Augmented p-GSK-3beta induced neuroprotective effects
      similar to those of EA pretreatment. In contrast, dampened p-GSK-3beta could
      reverse the neuroprotective effects of EA. In addition, the increase in p-GSK
      3beta by EA was abolished by AdipoR1 knockdown. We conclude that EA pretreatment
      increases the production of APN, which induce protective effects against cerebral
      ischemia-reperfusion injury through neuronal AdipoR1-mediated phosphorylation of
      GSK-3beta in diabetic mice.

PMID- 24915971
TI  - Who is India's new health minister?

PMID- 24915970
TI  - The impact of sleep duration on adolescent development: a genetically informed
      analysis of identical twin pairs.
AB  - Recent work provides evidence that reduced sleep duration has detrimental effects
      on a range of developmentally related outcomes during adolescence. Yet, the
      potential confounding influence of genetic and shared environmental effects has
      not been sufficiently addressed. This study addresses this issue by analyzing
      cross-sectional data from the twin sub-sample of the first wave of the National
      Longitudinal Study of Adolescent Health [N ~ 287 MZ (monozygotic) twin pairs; 50%
      male; 22% Black; mean age = 15.75]. Associations between sleep duration (measured
      through two different strategies, one tapping number of hours slept at night and
      the other measuring weeknight bedtimes) and seven outcomes (self-control,
      depressive symptoms, suicidal ideation, body mass index, violent delinquency, non
      violent delinquency, and drug use) were estimated. Consistent with prior
      research, associations between sleep duration and several outcomes were
      statistically significant when using standard social science analytic methods.
      Yet, when employing a methodology that accounts for genetic and shared
      environmental influences, some of these associations were reduced to non
      significance. Still, two consistent associations remained in that participants
      who reported sleeping fewer hours at night (or who reported later bedtimes)
      exhibited lower levels of self-control and more depressive symptoms. Implications
      of the findings and directions for future research are discussed.

PMID- 24915969
TI  - BK Induces cPLA2 Expression via an Autocrine Loop Involving COX-2-Derived PGE2 in
      Rat Brain Astrocytes.
AB  - Bradykinin (BK) is a proinflammatory mediator and elevated in several brain
      injury and inflammatory diseases. The deleterious effects of BK on brain
      astrocytes may aggravate brain inflammation mediated through the upregulation of
      cytosolic phospholipase A2 (cPLA2)/cyclooxygenase-2 (COX-2)-derived prostaglandin
      E2 (PGE2) production. However, the signaling mechanisms underlying BK-induced
      cPLA2 expression in brain astrocytes remain unclear. Herein, we investigated the
      effects of activation of cPLA2/COX-2 system on BK-induced cPLA2 upregulation in
      rat brain astrocytes (RBA-1). The data obtained with Western blotting, RT-PCR,
      and immunofluorescent staining analyses showed that BK-induced de novo cPLA2
      expression was mediated through activation of cPLA2/COX-2 system. Upregulation of
      native cPLA2/COX-2 system by BK through activation of PKCdelta, c-Src, MAPKs
      (ERK1/2 and JNK1/2) cascades led to PGE2 biosynthesis and release. Subsequently,
      the released PGE2 induced cPLA2 expression via the same signaling pathways
      (PKCdelta, c-Src, ERK1/2, and JNK1/2) and then activated the cyclic AMP response
      element-binding protein (CREB) via B2 BK receptor-mediated cPLA2/COX-2 system
      derived PGE2/EP-dependent manner. Finally, upregulation of cPLA2 by BK may
      promote more PGE2 production. These results demonstrated that in RBA-1,
      activation of CREB by PGE2/EP-mediated PKCdelta/c-Src/MAPK cascades is essential
      for BK-induced de novo cPLA2 protein. More importantly, upregulation of cPLA2 by
      BK through native cPLA2/COX-2 system may be a positive feedback mechanism that
      enhances prolonged brain inflammatory responses. Understanding the mechanisms of
      cPLA2/COX-2 system upregulated by BK on brain astrocytes may provide rational
      therapeutic interventions for brain injury and inflammatory diseases. 

PMID- 24915974
TI  - New frontiers in the management of acute coronary syndromes: cangrelor and
      elinogrel.
AB  - The activation and aggregation of platelets at sites of vascular injury or near
      to implanted stent are pivotal in the development of thrombotic events during and
      after an acute coronary syndrome (ACS) or a percutaneous coronary intervention
      (PCI). For that reason, an exclusively oral dual antiplatelet treatment regimen
      with platelet P2Y12 receptor antagonists in addition to the cyclooxygenase
      inhibitor aspirin has become the cornerstone of treatment in that contest.
      However, every trial underlines the same problem: if maximizing antiplatelet
      therapy significantly attenuates ischemic events in patients with coronary artery
      disease, on the other side it may also increase bleeding phenomena. These
      limitations have prompted a search for novel antiplatelet agents with a more
      favorable risk-benefit ratio. Moreover, an early onset of action is desirable
      during PCI and an early offset after bleeding events. Two novel antiplatelet
      agents, Cangrelor and Elinogrel, are available in intravenous form (Elinogrel
      also in oral form) and expand this context. Recent trials have tested them
      against Clopidogrel regarding efficacy and safety outcomes.This review aimed at
      providing an overview on intravenous emerging compounds and recent patents in the
      setting of ACS and PCI. 

PMID- 24915972
TI  - Everolimus-eluting stents improve vascular response in a diabetic animal model.
AB  - BACKGROUND: Preclinical evaluation of the vascular response of drug-eluting
      stents is limited especially in the setting of diabetes mellitus preventing the
      evaluation of changes in drug-eluting stent design and eluted drugs after
      clinical use. METHODS AND RESULTS: Cultured human aortic endothelial cells were
      used to assess the differences between sirolimus and its analog, everolimus, in
      the setting of hyperglycemia on various cellular functions necessary for
      endothelial recovery. A diabetic rabbit model of iliac artery stenting was used
      to compare histological and morphometric characteristics of the vascular response
      to everolimus-eluting, sirolimus-eluting, and bare metal stent placement. Under
      hyperglycemic conditions, sirolimus impaired human aortic endothelial cell
      barrier function, migration, and proliferation to a greater degree compared with
      everolimus. In our in vivo model of diabetes mellitus, endothelialization at 28
      days was significantly lower and endothelial integrity was impaired in sirolimus
      eluting stent compared with both everolimus-eluting and bare metal stents.
      Neointimal area, uncovered struts, and fibrin deposition were significantly
      higher in sirolimus-eluting compared with everolimus-eluting and bare metal
      stents. CONCLUSIONS: Use of everolimus-eluting stent results in improved vascular
      response in our preclinical models of diabetes mellitus.

PMID- 24915973
TI  - Neutrophil-derived microparticles induce myeloperoxidase-mediated damage of
      vascular endothelial cells.
AB  - BACKGROUND: Upon activation neutrophil releases microparticles - small plasma
      membrane vesicles that contain cell surface proteins and cytoplasmic matter, with
      biological activities. In this study we investigated the potential role of
      myeloperoxidase in the endothelial cell injury caused by neutrophil-derived
      microparticles. RESULTS: Microparticles were produced by activating human
      neutrophils with a calcium ionophore and characterized by flow cytometry and
      transmission and scanning electron microscopy. Myeloperoxidase activity was
      measured by luminol-dependent chemiluminescence. Neutrophil microparticles
      induced injuries and morphological alterations in human umbilical vein
      endothelial cells (HUVECs) were evaluated by microscopy and flow cytometry.
      Neutrophil microparticles were characterized as structures bounded by lipid
      bilayers and were less than 1 MUm in diameter. The microparticles also expressed
      CD66b, CD62L and myeloperoxidase, which are all commonly expressed on the surface
      of neutrophils, as well as exposition of phosphatidylserine. The activity of the
      myeloperoxidase present on the microparticles was confirmed by hypochlorous acid
      detection. This compound is only catalyzed by myeloperoxidase in the presence of
      hydrogen peroxide and chloride ion. The addition of sodium azide or taurine
      inhibited and reduced enzymatic activity, respectively. Exposure of HUVEC to
      neutrophil microparticles induced a loss of cell membrane integrity and
      morphological changes. The addition of sodium azide or myeloperoxidase-specific
      inhibitor-I consistently reduced the injury to the endothelial cells. Taurine
      addition reduced HUVEC morphological changes. CONCLUSIONS: We have demonstrated
      the presence of active myeloperoxidase in neutrophil microparticles and that the
      microparticle-associated myeloperoxidase cause injury to endothelial cells.
      Hence, the microparticle-associated myeloperoxidase-hydrogen peroxide-chloride
      system may contribute to widespread endothelial cell damage in conditions of
      neutrophil activation as observed in vasculitis and sepsis.

PMID- 24915975
TI  - Does waist circumference uncorrelated with BMI add valuable information?
AB  - BACKGROUND: Estimation of relative contribution of Body Mass Index (BMI) and
      waist circumference (WC) on health outcomes requires a regression model that
      includes both obesity metrics. But, multicollinearity could yield biased
      estimates. METHODS: To address the multicollinearity issue between BMI and WC, we
      used the residual model approach. The standard WC (Y-axis) was regressed on the
      BMI (X-axis) to obtain residual WC. Data from two adult population surveys
      (Nunavik Inuit and James Bay Cree) were analysed to evaluate relative effect of
      BMI and WC on four cardiometabolic risk factors: insulin, triglycerides, systolic
      blood pressure and high-density lipoprotein levels. RESULTS: In multivariate
      models, standard WC and BMI were significantly associated with cardiometabolic
      outcomes. Residual WC was not linked with any outcomes. The BMI effect was
      weakened by including standard WC in the model, but its effect remained unchanged
      if residual WC was considered. CONCLUSIONS: The strong correlation between
      standard WC and BMI does not allow assessment of their relative contributions to
      health in the same model without a risk of making erroneous estimations. By
      contrast with BMI, fat distribution (residual WC) does not add valuable
      information to a model that already contains overall adiposity (BMI) in Inuit and
      Cree.

PMID- 24915977
TI  - Mechanical reinforcement of epoxy with self-assembled synthetic clay in smectic
      order.
AB  - Epoxy films containing self-assembled 2D colloidal alpha-zirconium phosphate
      nanoplatelets (ZrP) in smectic order were prepared using a simple, energy
      efficient fabrication process suitable to industrial processing. The ZrP
      nanoplatelets form a chiral smectic mesophase with simultaneous lamellar order
      and helical arrangements in epoxy. The epoxy nanocomposite films are transparent
      and flexible and exhibit exceptionally high tensile modulus and strength. The
      findings have broad implications for development of multifunctional materials for
      engineering applications. 

PMID- 24915978
TI  - Photosensing performance of branched CdS/ZnO heterostructures as revealed by in
      situ TEM and photodetector tests.
AB  - CdS/ZnO branched heterostructures have been successfully synthesized by combining
      thermal vapour deposition and a hydrothermal method. Drastic optoelectronic
      performance enhancement of such heterostructures was revealed, compared to plain
      CdS nanobelts, as documented by comparative in situ optoelectronic studies on
      corresponding individual nanostructures using an originally designed laser
      compatible transmission electron microscopy (TEM) technique. Furthermore,
      flexible thin-film based photodetectors based on standard CdS nanobelts and newly
      prepared CdS/ZnO heterostructures were fabricated on PET substrates, and
      comparative photocurrent and photo-responsivity measurements thoroughly verified
      the in situ TEM results. The CdS/ZnO branched heterostructures were found to have
      better performance than standard CdS nanobelts for optoelectronic applications
      with respect to the photocurrent to dark current ratio and responsivity. 

PMID- 24915976
TI  - Caenorhabditis elegans male sensory-motor neurons and dopaminergic support cells
      couple ejaculation and post-ejaculatory behaviors.
AB  - The circuit structure and function underlying post-coital male behaviors remain
      poorly understood. Using mutant analysis, laser ablation, optogenetics, and Ca2+
      imaging, we observed that following C. elegans male copulation, the duration of
      post-coital lethargy is coupled to cellular events involved in ejaculation. We
      show that the SPV and SPD spicule-associated sensory neurons and the spicule
      socket neuronal support cells function with intromission circuit components,
      including the cholinergic SPC and PCB and the glutamatergic PCA sensory-motor
      neurons, to coordinate sex muscle contractions with initiation and continuation
      of sperm movement. Our observations suggest that the SPV and SPD and their
      associated dopamine-containing socket cells sense the intrauterine environment
      through cellular endings exposed at the spicule tips and regulate both sperm
      release into the hermaphrodite and the recovery from post-coital lethargy.

PMID- 24915980
TI  - Imaging modalities for the classification of gout: systematic literature review
      and meta-analysis.
AB  - BACKGROUND: Although there has been major progress in gout imaging, no gout
      classification criteria currently include advanced imaging techniques. OBJECTIVE:
      To examine the usefulness of imaging modalities in the classification of gout
      when compared to monosodium urate (MSU) crystal confirmation as the gold
      standard, in order to inform development of new gout classification criteria.
      METHODS: We systematically reviewed the published literature concerning the
      diagnostic performance of plain film radiography, MRI, ultrasound (US),
      conventional CT and dual energy CT (DECT). Only studies with MSU crystal
      confirmation as the gold standard were included. When more than one study
      examined the same imaging feature, the data were pooled and summary test
      characteristics were calculated. RESULTS: 11 studies (9 manuscripts and 2 meeting
      abstracts) satisfied the inclusion criteria. All were set in secondary care, with
      mean gout disease duration of at least 7 years. Three features were examined in
      more than one study: the double contour sign (DCS) on US, tophus on US, and MSU
      crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US
      DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus,
      were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were
      0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively. CONCLUSIONS: US and
      DECT show promise for gout classification but the few studies to date have mostly
      been in patients with longstanding, established disease. The contribution of
      imaging over clinical features for gout classification criteria requires further
      examination.

PMID- 24915982
TI  - Role of hydrophobicity on self-assembly by peptide amphiphiles via molecular
      dynamics simulations.
AB  - Using a novel coarse-grained model, large-scale molecular dynamics simulations
      were performed to examine self-assembly of 800 peptide amphiphiles (sequence
      palmitoyl-V3A3E3). Under suitable physiological conditions, these molecules
      readily assemble into nanofibers leading to hydrogel construction as observed in
      experiments. Our simulations capture this spontaneous self-assembly process,
      including formation of secondary structure, to identify morphological transitions
      of distinctive nanostructures. As the hydrophobic interaction is increased,
      progression from open networks of secondary structures toward closed cylindrical
      nanostructures containing either beta-sheets or random coils are observed.
      Moreover, temperature effects are also determined to play an important role in
      regulating formation of secondary structures within those nanostructures. These
      understandings of the molecular interactions involved and the role of
      environmental factors on hydrogel formation provide useful insight for
      development of innovative smart biomaterials for biomedical applications. 

PMID- 24915981
TI  - Attenuation of serotonin-induced itch responses by inhibition of endocannabinoid
      degradative enzymes, fatty acid amide hydrolase and monoacylglycerol lipase.
AB  - Itch and pain are two irritating sensations sharing a lot in common. Considering
      the antinociceptive effects of blockade of endocannabinoid degrading enzymes in
      pain states, we attempted to reduce scratching behavior by endocannabinoid
      modulation, i.e. by inhibiting fatty acid amide hydrolase (FAAH),
      monoacylglycerol lipase (MAGL), or cellular uptake of endocannabinoids.
      Scratching behavior was induced by intradermal injection of serotonin to Balb/c
      mice. URB597 (10 mg/kg, i.p.), a FAAH inhibitor, JZL184 (16 mg/kg, i.p.), a MAGL
      inhibitor, and AM404 (10 mg/kg, i.p.), an endocannabinoid transport inhibitor,
      were given to evaluate the effects of endocannabinoid modulation on scratching
      responses. Then, the CB1 receptor antagonist, AM251 (1 mg/kg, i.p.), and the CB2
      receptor antagonist, SR144528 (1 mg/kg, i.p.), were administered to determine
      whether cannabinoid receptors mediate these effects. URB597 and JZL184, but not
      AM404, attenuated serotonin-induced scratches. The inhibitory effect of URB597
      was reversed by SR144528, but cannabinoid receptor antagonists had no other
      effects on modulation by the inhibitors. We propose that augmenting the
      endocannabinoid tonus by inhibition of degradative enzymes, FAAH and MAGL, but
      not cellular uptake, may be a novel target for the development of antipruritic
      agents.

PMID- 24915983
TI  - Add-on ezetimibe reduces small dense low-density lipoprotein cholesterol levels
      without affecting absorption of eicosapentaenoic acid in patients with coronary
      artery disease: a pilot study.
AB  - BACKGROUND: Residual risk of cardiovascular disease from increased small dense
      low-density lipoprotein (sdLDL)-cholesterol levels and low n-3 polyunsaturated
      fatty acid (PUFA) levels is a considerable therapeutic issue. The purpose of this
      study was to evaluate the effect of ezetimibe as an add-on to statins and
      supplemental eicosapentaenoic acid (EPA) on sdLDL cholesterol and absorption of
      EPA in patients with coronary artery disease. METHODS: The study population
      consisted of ten male patients who were concurrently receiving statins and EPA
      1,800 mg/day. Serum lipids and PUFAs, including EPA and arachidonic acid, were
      measured in blood samples collected before ezetimibe (baseline), 4 weeks after
      starting 10-mg/day ezetimibe, and 4 weeks after discontinuing ezetimibe. RESULTS:
      Ezetimibe significantly decreased sdLDL-cholesterol levels after 4 weeks of
      treatment (baseline 35 +/- 13 mg/dl; treatment 27 +/- 9 mg/dl), but the levels
      returned to baseline after discontinuation of ezetimibe (37 +/- 13 mg/dl). The
      concentration of EPA did not significantly change during the study. CONCLUSION:
      Ezetimibe shows great promise as an add-on therapy to statins to reduce sdLDL
      cholesterol-related residual risk of cardiovascular disease without affecting
      absorption of supplemental EPA in patients with coronary artery disease.

PMID- 24915985
TI  - Management of a transbronchial cryobiopsy using the i-gel(r) airway and the Arndt
      endobronchial blocker.

PMID- 24915984
TI  - Vacuolar protein sorting 35 (Vps35) rescues locomotor deficits and shortened
      lifespan in Drosophila expressing a Parkinson's disease mutant of Leucine-Rich
      Repeat Kinase 2 (LRRK2).
AB  - BACKGROUND: Parkinson's disease (PD) is the most common movement
      neurodegenerative movement disorder. An incomplete understanding of the molecular
      pathways involved in its pathogenesis impedes the development of effective
      disease-modifying treatments. To address this gap, we have previously generated a
      Drosophila model of PD that overexpresses PD pathogenic mutant form of the second
      most common causative gene of PD, Leucine-Rich Repeat Kinase 2 (LRRK2). FINDINGS:
      We employed this model in a genetic modifier screen and identified a gene that
      encodes for a core subunit of retromer - a complex essential for the sorting and
      recycling of specific cargo proteins from endosomes to the trans-Golgi network
      and cell surface. We present evidence that overexpression of the Vps35 or Vps26
      component of the cargo-recognition subunit of the retromer complex ameliorates
      the pathogenic mutant LRRK2 eye phenotype. Furthermore, overexpression of Vps35
      or Vps26 significantly protects from the locomotor deficits observed in mutant
      LRRK2 flies, as assessed by the negative geotaxis assay, and rescues their
      shortened lifespan. Strikingly, overexpressing Vps35 alone protects from toxicity
      of rotenone, a neurotoxin commonly used to model parkinsonism, both in terms of
      lifespan and locomotor activity of the flies, and this protection is sustained
      and even augmented in the presence of mutant LRRK2. Finally, we demonstrate that
      knocking down expression of Vps35 in dopaminergic neurons causes a significant
      locomotor impairment. CONCLUSIONS: From these results we conclude that LRRK2
      plays a role in the retromer pathway and that this pathway is involved in PD
      pathogenesis.

PMID- 24915986
TI  - Maternal age and initial beta-hCG levels predict pregnancy outcome after single
      vitrified-warmed blastocyst transfer.
AB  - PURPOSE: We retrospectively examined a large cohort of females who underwent
      single blastocyst transfer to determine if initial beta-human chorionic
      gonadotrophin (beta-hCG) levels on day 7 after single vitrified-warmed blastocyst
      transfer (SVBT) could be used to predict pregnancy outcome. METHODS: The
      treatment cycles that gave rise to the early pregnancies included in this study
      were performed from 2004 to 2011 in a private infertility center. In SVBT cycles,
      embryos were transferred during a natural cycle or after endometrial preparation
      with exogenous estrogen and progesterone. A total of 11,458 cycles with beta-hCG
      levels >=1.0 UI/ml on day 7 after SVBT were evaluated. The proportion of live
      births per positive beta-hCG cycle was established for 10 beta-hCG ranges in 3
      different age groups (Group A: 21-34 years old; Group B: 35-39 years old; Group
      C: 40-44 years old). RESULTS: The proportion of live births gradually increased
      from 1.5 to 93.7%, 0.8 to 87.9%, and 0.6 to 76.2% in Groups A, B, and C,
      respectively. For each range of beta-hCG levels, the proportion of live births
      was higher for the younger age group, which reflected the increased risk of early
      pregnancy loss with advancing female age. CONCLUSIONS: beta-hCG levels on day 7
      after SVBT, in conjunction with maternal age, may be used to predict pregnancy
      outcomes.

PMID- 24915987
TI  - Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron
      concentration and comparison with R2 Ferriscan.
AB  - BACKGROUND: There is a need to standardise non-invasive measurements of liver
      iron concentrations (LIC) so clear inferences can be drawn about body iron levels
      that are associated with hepatic and extra-hepatic complications of iron
      overload. Since the first demonstration of an inverse relationship between biopsy
      LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR
      technology has advanced dramatically with a shorter minimum echo-time, closer
      inter-echo spacing and constant repetition time. These important advances allow
      more accurate calculation of liver T2* especially in patients with high LIC.
      METHODS: Here, we used an optimised liver T2* sequence calibrated against 50
      liver biopsy samples on 25 patients with transfusional haemosiderosis using
      ordinary least squares linear regression, and assessed the method reproducibility
      in 96 scans over an LIC range up to 42 mg/g dry weight (dw) using Bland-Altman
      plots. Using mixed model linear regression we compared the new T2*-LIC with R2
      LIC (Ferriscan) on 92 scans in 54 patients with transfusional haemosiderosis and
      examined method agreement using Bland-Altman approach. RESULTS: Strong linear
      correlation between ln(T2*) and ln(LIC) led to the calibration equation LIC =
      31.94(T2*)-1.014. This yielded LIC values approximately 2.2 times higher than the
      proof-of-concept T2* method. Comparing this new T2*-LIC with the R2-LIC
      (Ferriscan) technique in 92 scans, we observed a close relationship between the
      two methods for values up to 10 mg/g dw, however the method agreement was poor.
      CONCLUSIONS: New calibration of T2* against liver biopsy estimates LIC in a
      reproducible way, correcting the proof-of-concept calibration by 2.2 times. Due
      to poor agreement, both methods should be used separately to diagnose or rule out
      liver iron overload in patients with increased ferritin.

PMID- 24915988
TI  - Bayesian Checks on Cheating on Tests.
AB  - Posterior odds of cheating on achievement tests are presented as an alternative
      to [Formula: see text] values reported for statistical hypothesis testing for
      several of the probabilistic models in the literature on the detection of
      cheating. It is shown how to calculate their combinatorial expressions with the
      help of a reformulation of the simple recursive algorithm for the calculation of
      number-correct score distributions used throughout the testing industry. Using
      the odds avoids the arbitrary choice between statistical tests of answer copying
      that do and do not condition on the responses the test taker is suspected to have
      copied and allows the testing agency to account for existing circumstantial
      evidence of cheating through the specification of prior odds. 

PMID- 24915989
TI  - The perils of conducting meta-analyses of observational data.

PMID- 24915990
TI  - No evidence for LGV transmission among heterosexuals in Amsterdam, the
      Netherlands.
AB  - BACKGROUND: In recent years a few cases of lymphogranuloma venereum (LGV) in
      heterosexuals in Europe have been reported. It is not known whether LGV
      transmission among heterosexuals occurs on a wider scale. METHODS: Heterosexual
      male and female STI clinic clients (n = 587) in Amsterdam, the Netherlands, with
      a positive nucleic acid amplification test (NAAT) result for Chlamydia
      trachomatis (CT) were screened for IgA anti-MOMP in serum. If the value was above
      the cut-off index (2.0) the patient's CT positive urogenital, ocular or rectal
      sample(s) were selected and tested for LGV by an in-house LGV-specific NAAT.
      RESULTS: Sera of 126 patients were above 2.0 COI. Some patients had >1 CT
      positive sample. Samples could not be retrieved from 15 of the 126 persons, and 7
      samples that were found positive for CT in the diagnostic amplification process
      could not be confirmed and hence not typed. We did not find a single case of LGV
      infection in 123 urogenital, ocular or rectal samples from 104 patients.
      CONCLUSION: We found no indications for significant spread of LGV infection in
      heterosexuals in Amsterdam. Surveillance in females with cervical or anal CT
      infection is indicated to monitor LGV occurrence in heterosexuals.

PMID- 24915991
TI  - Tau pathology does not affect experience-driven single-neuron and network-wide
      Arc/Arg3.1 responses.
AB  - Intraneuronal neurofibrillary tangles (NFTs) - a characteristic pathological
      feature of Alzheimer's and several other neurodegenerative diseases - are
      considered a major target for drug development. Tangle load correlates well with
      the severity of cognitive symptoms and mouse models of tauopathy are behaviorally
      impaired. However, there is little evidence that NFTs directly impact
      physiological properties of host neurons. Here we used a transgenic mouse model
      of tauopathy to study how advanced tau pathology in different brain regions
      affects activity-driven expression of immediate-early gene Arc required for
      experience-dependent consolidation of long-term memories. We demonstrate in vivo
      that visual cortex neurons with tangles are as likely to express comparable
      amounts of Arc in response to structured visual stimulation as their neighbors
      without tangles. Probability of experience-dependent Arc response was not
      affected by tau tangles in both visual cortex and hippocampal pyramidal neurons
      as determined postmortem. Moreover, whole brain analysis showed that network-wide
      activity-driven Arc expression was not affected by tau pathology in any of the
      brain regions, including brain areas with the highest tangle load. Our findings
      suggest that intraneuronal NFTs do not affect signaling cascades leading to
      experience-dependent gene expression required for long-term synaptic plasticity. 

PMID- 24915992
TI  - Fungal metabolite nigerloxin ameliorates diabetic nephropathy and gentamicin
      induced renal oxidative stress in experimental rats.
AB  - Elevated polyol pathway enzyme activities and oxidative stress play an important
      role in the development and progression of diabetic nephropathy. Here, we
      investigated the beneficial influence of nigerloxin, a fungal metabolite and a
      potent aldose reductase inhibitor and free radical scavenger in the kidney of
      streptozotocin-induced diabetic rats. A group of diabetic rats was orally
      administered with nigerloxin for 30 days (100 mg/kg). Diabetic rats showed
      increased lipid peroxides, advanced glycation end products (AGEs), elevated
      activities of polyol pathway enzymes, and lowered antioxidant defense system in
      kidney. Administration of nigerloxin decreased kidney lipid peroxides and AGEs.
      Activities of polyol pathway enzymes were reduced while activities of all
      antioxidant enzymes, glutathione, and ascorbic acid were elevated in the kidney
      of nigerloxin-treated diabetic rats. We also investigated antioxidant potential
      of nigerloxin in gentamicin-induced nephrotoxicity in Wistar rats. Groups of rats
      were orally administered with nigerloxin for 8 days (25 mg or 100 mg kg(-1) body
      weight day(-1)) along with gentamicin (80 mg/kg, i.p., for 8 days). Gentamicin
      induced increase in lipid peroxides, decrease in glutathione and activities of
      antioxidant enzymes in the kidney, and increase in blood creatinine, and urea
      concentrations were significantly countered by nigerloxin treatment. Thus, the
      results indicated the beneficial influence of nigerloxin on polyol pathway and
      oxidative stress associated with diabetes, which are implicated in ameliorating
      the development of diabetic nephropathy. Nigerloxin also ameliorated oxidative
      stress induced by gentamicin in the renal tissue. 

PMID- 24915994
TI  - High-quality green tea leaf production by artificial cultivation under growth
      chamber conditions considering amino acids profile.
AB  - The current study focused on the tea plant (Camellia sinensis) as a target for
      artificial cultivation because of the variation in its components in response to
      light conditions. We analyzed its sensory quality by multi-marker profiling using
      multicomponent data based on metabolomics to optimize the conditions of light and
      the environment during cultivation. From the analysis of high-quality tea samples
      ranked in a tea contest, the ranking predictive model was created by the partial
      least squares (PLS) regression analysis to examine the correlation between the
      amino-acid content (X variables) and the ranking in the tea contest (Y
      variables). The predictive model revealed that glutamine, arginine, and theanine
      were the predominant amino acids present in high-ranking teas. Based on this
      result, we established a cover-culture condition (i.e., a low-light intensity
      condition) during the later stage of the culture process and obtained
      artificially cultured tea samples, which were predicted to be high-quality teas.
      The aim of the current study was to optimize the light conditions for the
      cultivation of tea plants by performing data analysis of their sensory qualities
      through multi-marker profiling in order to facilitate the development of high
      quality teas by plant factories. 

PMID- 24915993
TI  - Interaction between Nm23 and the tumor suppressor VHL.
AB  - Among the anti-tumor genes (tumor suppressors and metastasis suppressors), the
      von-Hippel Lindau gene and the Nm23 family of genes are among the more intriguing
      ones. Both are small (long and short forms of VHL are 30 and 19 kD, respectively,
      and Nm23 is ~17 kD), and both possess diverse molecular and cellular functions.
      Despite extensive studies, the entire spectra of functions and the molecular
      function-phenotype correlation of these two proteins have not been completely
      elucidated. In this report, we present data showing these two proteins interact
      physically. We also summarize and confirm the previous studies that demonstrated
      the endocytic function of these two genes and further show that the endocytic
      function of VHL is mediated through the activity of Nm23. These functional and
      molecular interactions are evolutionarily conserved from Drosophila to human. 

PMID- 24915995
TI  - The potential for the Farman entrainer to be used with a pediatric t-piece: a
      bench study.
AB  - OBJECTIVES: To determine the limits of performance of the Farman Entrainer used
      with the t-piece for pediatric anesthesia in areas with limited oxygen supplies.
      METHODS: Bench tests were conducted with different system configurations, normal
      and 'emergency situation' ventilation patterns were replicated to reproduce a
      range of circumstances the anesthetist may encounter. RESULTS: We found that
      Fi0(2) rises and flow decreases with increasing CPAP, but probably within safe
      limits. A one way valve is essential to avoid high concentration of volatile
      agent. Very high ventilation rates reduce flow significantly. Increasing oxygen
      input from an oxygen concentrator increases the flow output but does not increase
      Fi0(2). CONCLUSION: The basic characteristics of the system are within normally
      accepted parameters for t-piece anesthesia, safety in practice requires to be
      demonstrated by a clinical study.

PMID- 24915996
TI  - Conradi-Hunermann-Happle syndrome: a novel heterozygous missense mutation,
      c.204G>T (p.W68C).
AB  - Conradi-Hunermann-Happle syndrome (X-linked dominant chondrodysplasia punctata,
      CDPX2 [Online Mendelian Inheritance in Man 302960]) is a rare genodermatosis that
      presents with blaschkolinear ichthyosis, cicatricial alopecia, chondrodysplasia
      punctata, asymmetric shortening of the bones, and cataracts. In this case report
      we describe a child presenting with a patterned alopecia in which supplementary
      signs and clinical examination of the mother led to the suspicion of Conradi
      Hunermann-Happle syndrome. Mutation analysis revealed a heterozygous novel
      missense mutation, c.204G>T (p.W68C), in exon 2. 

PMID- 24915997
TI  - Parents and their children's school lives--commentary on the special issue,
      'Parents' role in children's school lives'.

PMID- 24915998
TI  - A comparative analysis of dispersal syndromes in terrestrial and semi-terrestrial
      animals.
AB  - Dispersal, the behaviour ensuring gene flow, tends to covary with a number of
      morphological, ecological and behavioural traits. While species-specific
      dispersal behaviours are the product of each species' unique evolutionary
      history, there may be distinct interspecific patterns of covariation between
      dispersal and other traits ('dispersal syndromes') due to their shared
      evolutionary history or shared environments. Using dispersal, phylogeny and trait
      data for 15 terrestrial and semi-terrestrial animal Orders (> 700 species), we
      tested for the existence and consistency of dispersal syndromes across species.
      At this taxonomic scale, dispersal increased linearly with body size in
      omnivores, but decreased above a critical length in herbivores and carnivores.
      Species life history and ecology significantly influenced patterns of
      covariation, with higher phylogenetic signal of dispersal in aerial dispersers
      compared with ground dwellers and stronger evidence for dispersal syndromes in
      aerial dispersers and ectotherms, compared with ground dwellers and endotherms.
      Our results highlight the complex role of dispersal in the evolution of species
      life-history strategies: good dispersal ability was consistently associated with
      high fecundity and survival, and in aerial dispersers it was associated with
      early maturation. We discuss the consequences of these findings for species
      evolution and range shifts in response to future climate change. 

PMID- 24916000
TI  - Disappearance of circulating autoantibodies to RNA polymerase III in a patient
      with systemic sclerosis successfully treated with corticosteroid and
      methotrexate.

PMID- 24915999
TI  - Local architecture of the vastus intermedius is a better predictor of knee
      extension force than that of the other quadriceps femoris muscle heads.
AB  - The purpose of this study was to determine whether the muscle architecture of
      each head of the quadriceps femoris (QF) at multiple regions can be used to
      predict knee extension force. Muscle thickness and pennation angle were measured
      using sonographic images from multiple regions on each muscle of the QF with the
      knee flexed to 90 degrees . The fascicle lengths of the rectus femoris (RF),
      vastus lateralis (VL) and vastus intermedius (VI) muscles were estimated based on
      sonographic images taken along the length of the thigh. The muscle architecture
      of the vastus intermedius was determined in two separate locations using
      sonographic images of the anterior (ant-VI) and lateral portions (lat-VI). The
      maximal voluntary contraction (MVC) was measured during isometric knee extension
      at a knee joint angle of 90 degrees . The relationship between MVC force and
      muscle architecture was examined using a stepwise linear regression analysis with
      MVC force as the dependent variable. The muscle thickness of the ant-VI was
      selected as an independent variable in the first step of the linear regression
      analysis (R(2) = 0.66, P<0.01). In the second step, pennation angle of the lat-VI
      was added to the model (R(2) = 0.91, P<0.01). These results suggest that among
      the four muscles that make up the QF, the muscle architecture of the VI is the
      best predictor of knee extension force.

PMID- 24916001
TI  - Preparation of paraoxonase-1 liposomes and studies on their in vivo
      pharmacokinetics in rats.
AB  - A liposome formulation of the enzyme paraoxonase-1 (PON1) was prepared for
      purposes of prolonging and maintaining its activity in vivo. Following
      purification of PON1 from rabbit serum, liposomes containing PON1 (L-PON1) were
      prepared using a film-dispersion method with a soybean phospholipid-cholesterol
      mixture (5 : 1, w/w). The pharmacokinetic behaviour of conventional injectable
      PON1 and L-PON1 was compared following a single intravenous injection in rats.
      The enzyme activity of PON1 and its pharmacokinetic parameters were calculated
      based on a two-compartment model following conventional injection. The level of
      PON1 encapsulation in L-PON1 was 86.20 +/- 3.12%. The particle size distribution
      of L-PON1 was a narrow unimodal form, with an average diameter of 126 nm. The
      results suggest that compared with conventional injectable PON1, L-PON1 has an
      improved half-life and enhanced enzyme activity in rats. In conclusion, PON1 can
      be encapsulated into a lipid bilayer for enhanced stability. 

PMID- 24916002
TI  - A prospective study of hepatitis C incidence in Australian prisoners.
AB  - AIMS: To document the relationships between injecting drug use, imprisonment and
      hepatitis C virus (HCV) infection. DESIGN: Prospective cohort study. SETTING:
      Multiple prisons in New South Wales, Australia. PARTICIPANTS: HCV seronegative
      prisoners with a life-time history of injecting drug use (IDU) were enrolled and
      followed prospectively (n = 210) by interview and HCV antibody and RNA testing 6
      12-monthly for up to 4 years when in prison. MEASUREMENTS: HCV incidence was
      calculated using the person-years method. Cox regression was used to identify
      predictors of incident infection using time-dependent covariates. RESULTS: Almost
      half the cohort reported IDU during follow-up (103 subjects; 49.1%) and 65 (31%)
      also reported sharing of the injecting apparatus. There were 38 HCV incident
      cases in 269.94 person-years (py) of follow-up with an estimated incidence of
      14.08 per 100 py [confidence interval (CI) = 9.96-19.32]. Incident infection was
      associated independently with Indigenous background, injecting daily or more and
      injecting heroin. Three subjects were RNA-positive and antibody-negative at the
      incident time-point, indicating early infection, which provided a second
      incidence estimate of 9.4%. Analysis of continuously incarcerated subjects (n =
      114) followed over 126.73 py, identified 13 new HCV infections (10.26 per 100 py,
      CI = 5.46-17.54), one of which was an early infection case. Bleach-cleansing of
      injecting equipment and opioid substitution treatment were not associated with a
      significant reduction in incidence. CONCLUSIONS: In New South Wales, Australia,
      imprisonment is associated with high rates of hepatitis C virus transmission.
      More effective harm reduction interventions are needed to control HCV in prison
      settings.

PMID- 24916003
TI  - Factors influencing root canal retreatment strategies by general practitioners
      and specialists in Australia.
AB  - AIM: To evaluate the effect of tooth radiographic features on root canal
      retreatment strategies used by general dental practitioners and dental
      specialists in Australia. METHODS: A descriptive survey study comprising a web
      based questionnaire was sent to general dental practitioners and specialists. The
      questionnaire diagrammatically represented six different clinical scenarios with
      variables including type of coronal restoration, quality of root filling and the
      size and presence of a periapical radiolucency. Treatment options included no
      treatment, orthograde retreatment, periapical surgery and replacement with an
      implant. For each of the six scenarios, the participant was asked to select a
      minimum size cut-off point where treatment would be initiated and also indicate
      the preferred treatment option. RESULTS: A total of 639 questionnaires were
      submitted online. In teeth without a cast core restoration, the quality of root
      filling influenced the selection of no treatment as an option (P < 0.001). The
      presence of a cast post/core restoration influenced both the treatment cut-off
      point and treatment option, with more practitioners selecting larger lesions as
      cut-off points (P < 0.001) and more treatment options involving both implant
      placement (P < 0.001) and periapical surgery (P < 0.001). With more complex
      treatment planning (i.e. cast post/core restorations and inadequate root
      filling), general practitioners proposed implant placement more readily compared
      with specialists (P < 0.001). CONCLUSIONS: General practitioners and specialists
      vary their root canal retreatment strategies according to quality of root filling
      and type of coronal restoration. Whilst all clinical scenarios could be managed
      by contemporary endodontic techniques, teeth were still treatment planned for
      extraction and replacement with an implant. This may be due to the fact that
      implants are heavily marketed by the dental industry and with more stringent
      outcome criteria applied to the assessment of root canal treatment compared with
      implant placement, evidence-based decision-making may be distorted. Future
      emphasis should be placed on changing practitioners' attitudes towards the
      retention of salvageable teeth by contemporary endodontic measures.

PMID- 24916004
TI  - The influences of larger physical constitutions including obesity on the amount
      of urine protein excretion in primary glomerulonephritis: research of the Japan
      Renal Biopsy Registry.
AB  - BACKGROUND: This study aimed to describe the influences of larger physical
      constitutions including obesity on the amount of urine protein excretion (AUPE)
      in primary glomerulonephritis. The distinct effects on the AUPE in various types
      of glomerulonephritis were evaluated. METHODS: Using the database of the Japan
      Renal Biopsy Registry (J-RBR) from 2007 to 2010, 4060 cases with primary
      glomerulonephritis including MCNS, FSGS, MN, MPGN, IgAN, and non-IgA were
      reviewed. The AUPEs were compared between high and low Body Mass Index (BMI)
      groups, and larger and smaller body surface area (BSA) groups using the indexes
      of BMI 25.0 kg/m(2) and BSA 1.73 m(2) in all cases and in each histological
      group. Multivariable analysis was performed to evaluate the predominant
      contributors to the AUPE. RESULTS: The larger physical constitution groups (BMI
      >=25.0 kg/m(2) or BSA >=1.73 m(2)) had significantly higher AUPEs in all cases
      with primary glomerulonephritis. When compared in each histological group, the
      mean AUPEs were significantly higher in the larger physical constitution groups,
      excluding the FSGS and non-IgA groups. Multiple regression analysis revealed that
      the significant contributors to the AUPE were BMI and BSA in MCNS and MN, whereas
      BMI and BSA were not significant and mean blood pressure and serum creatinine
      were significant in FSGS and non-IgA. CONCLUSION: Larger physical constitutions
      including obesity had a significant impact on the increase in the AUPE in primary
      glomerulonephritis, especially in MCNS and MN. However, FSGS and non-IgA were
      distinct for having blood pressure and renal dysfunction as possibly the major
      causes of proteinuria.

PMID- 24916005
TI  - Ability of vitamin D receptor activator to prevent pulmonary congestion in
      advanced chronic kidney disease.
AB  - BACKGROUND: Vitamin D deficiency is common among patients with chronic kidney
      disease (CKD). However, the benefits of vitamin D supplementation versus vitamin
      D receptor activator (VDRA) administration have yet to be established. Recently,
      an association between activated vitamin D and cardiovascular factors was
      reported. To evaluate the benefits of VDRA in advanced CKD, we analyzed the
      association between VDRA administration and the prevalence of pulmonary
      congestion. METHODS: This retrospective, cross-sectional analysis included
      patients initiated on dialysis between October 2011 and September 2013 at 17
      Japanese institutions. Data from 952 participants were analyzed using a
      multivariate logistic regression model and a linear regression model. We also
      analyzed subgroup data for groups classified by selection of peritoneal dialysis
      or hemodialysis. RESULTS: Of the 952 participants, 303 patients received VDRA.
      VDRA administration was associated with a low prevalence of pulmonary congestion
      in the multivariate logistic regression model (odds ratio [OR], 0.64; 95 %
      confidence interval [CI], 0.44-0.94; P = 0.02). There was no significant
      association between VDRA administration and systolic blood pressure, diastolic
      blood pressure, or pulse pressure. Subgroup analysis revealed a tendency that
      VDRA administration was associated with low prevalence of pulmonary congestion in
      both groups. CONCLUSIONS: In this study, VDRA administration was associated with
      a low prevalence of pulmonary congestion in patients initiated on dialysis.
      Appropriate VDRA administration may prevent pulmonary congestion.

PMID- 24916006
TI  - Hidden in plain sight: bias towards sick patients when sampling patients with
      sufficient electronic health record data for research.
AB  - BACKGROUND: To demonstrate that subject selection based on sufficient laboratory
      results and medication orders in electronic health records can be biased towards
      sick patients. METHODS: Using electronic health record data from 10,000 patients
      who received anesthetic services at a major metropolitan tertiary care academic
      medical center, an affiliated hospital for women and children, and an affiliated
      urban primary care hospital, the correlation between patient health status and
      counts of days with laboratory results or medication orders, as indicated by the
      American Society of Anesthesiologists Physical Status Classification (ASA Class),
      was assessed with a Negative Binomial Regression model. RESULTS: Higher ASA Class
      was associated with more points of data: compared to ASA Class 1 patients, ASA
      Class 4 patients had 5.05 times the number of days with laboratory results and
      6.85 times the number of days with medication orders, controlling for age, sex,
      emergency status, admission type, primary diagnosis, and procedure. CONCLUSIONS:
      Imposing data sufficiency requirements for subject selection allows researchers
      to minimize missing data when reusing electronic health records for research, but
      introduces a bias towards the selection of sicker patients. We demonstrated the
      relationship between patient health and quantity of data, which may result in a
      systematic bias towards the selection of sicker patients for research studies and
      limit the external validity of research conducted using electronic health record
      data. Additionally, we discovered other variables (i.e., admission status, age,
      emergency classification, procedure, and diagnosis) that independently affect
      data sufficiency.

PMID- 24916007
TI  - Accounting for rate variation among lineages in comparative demographic analyses.
AB  - Genetic analyses of contemporary populations can be used to estimate the
      demographic histories of species within an ecological community. Comparison of
      these demographic histories can shed light on community responses to past
      climatic events. However, species experience different rates of molecular
      evolution, and this presents a major obstacle to comparative demographic
      analyses. We address this problem by using a Bayesian relaxed-clock method to
      estimate the relative evolutionary rates of 22 small mammal taxa distributed
      across northwestern North America. We found that estimates of the relative
      molecular substitution rate for each taxon were consistent across the range of
      sampling schemes that we compared. Using three different reference rates, we
      rescaled the relative rates so that they could be used to estimate absolute
      evolutionary timescales. Accounting for rate variation among taxa led to temporal
      shifts in our skyline-plot estimates of demographic history, highlighting both
      uniform and idiosyncratic evolutionary responses to directional climate trends
      for distinct ecological subsets of the small mammal community. Our approach can
      be used in evolutionary analyses of populations from multiple species, including
      comparative demographic studies. 

PMID- 24916009
TI  - Use of a single circuit to provide temporary mechanical respiratory and
      circulatory support in patients with LV apical thrombus and cardiogenic shock.
AB  - INTRODUCTION: Techniques to support patients with cardiogenic shock continue to
      improve. Patients with intracardiac thrombi pose a potential for additional
      complications. Novel methods of biventricular support are necessary to manage
      these patients. METHODS: Two patients with refractory cardiogenic shock and left
      ventricular apical thrombi underwent mechanical circulatory support (MCS) as a
      bridge to decision, with a left ventricular assist device (LVAD) and
      extracorporeal mechanical oxygenation (ECMO). Instead of the conventional LV
      apical cannulation for LVAD, the left atrium (LA) was cannulated. The LA cannula
      was then integrated with the ECMO circuit via a 'Y' connection to a percutaneous
      right atrial cannula, enabling optimal drainage of both sides into one circuit
      through a single CentriMag(r) pump and ECMO into the aorta. RESULTS: The first
      patient was converted to a durable LVAD and transplanted, while the second
      patient was explanted, after demonstrating significant LV recovery. CONCLUSION:
      We demonstrated the use of MCS as a bridge to decision in patients with LV
      thrombi, utilizing biatrial cannulation with a 'Y' connection to drain both right
      and left-sided circulation through a single circuit and pump.

PMID- 24916011
TI  - Characterization of the catabolic pathway for a phenylcoumaran-type lignin
      derived biaryl in Sphingobium sp. strain SYK-6.
AB  - Sphingobium sp. strain SYK-6 is capable of degrading various lignin-derived
      biaryls. We determined the catabolic pathway of a phenylcoumaran-type compound,
      dehydrodiconiferyl alcohol (DCA) in SYK-6, and identified some of the DCA
      catabolism genes. In SYK-6 cells, the alcohol group of DCA was oxidized to the
      carboxyl group, first at the B-ring side chain and then at the A-ring side chain.
      The resultant metabolite was degraded to 5-formylferulate and vanillin through
      the decarboxylation and the Calpha-Cbeta cleavage of the A-ring side chain. Based
      on the DCA catabolic pathway, alcohol dehydrogenase (ADH) and aldehyde
      dehydrogenase (ALDH) genes are thought to be involved in the conversion of DCA
      into an aldehyde intermediate (DCA-L) and the conversion of DCA-L into a
      carboxylic acid intermediate (DCA-C), respectively. SLG_05620 and SLG_24930,
      which belong to quinohemoprotein ADH and aryl ADH, respectively, were isolated as
      the genes responsible for the oxidation of DCA. In addition to these genes,
      multiple genes similar to SLG_05620 and SLG_24930 were found to confer DCA
      oxidation activities on Escherichia coli cells. In order to identify the DCA-L
      dehydrogenase genes, the DCA-L oxidation activities of the SYK-6 gene products of
      putative twenty-one ALDH genes were examined. Significant activities were
      observed in the four ALDH gene products, including the SLG_27910 product, which
      showed the highest activity. The disruption of SLG_27910 caused a decreased
      conversion of DCA-L, suggesting that SLG_27910 plays an important role in the DCA
      L oxidation. In conclusion, no specific gene seems to be solely responsible for
      the conversion of DCA and DCA-L, however, the multiple genes encoding
      quinohemoprotein ADH and aryl ADH genes, and four ALDH genes are probably
      involved in the conversion processes.

PMID- 24916010
TI  - Systematic review of facility-based sexual and reproductive health services for
      female sex workers in Africa.
AB  - BACKGROUND: Several biological, behavioural, and structural risk factors place
      female sex workers (FSWs) at heightened risk of HIV, sexually transmitted
      infections (STIs), and other adverse sexual and reproductive health (SRH)
      outcomes. FSW projects in many settings have demonstrated effective ways of
      altering this risk, improving the health and wellbeing of these women. Yet the
      optimum delivery model of FSW projects in Africa is unclear. This systematic
      review describes intervention packages, service-delivery models, and extent of
      government involvement in these services in Africa. METHODS: On 22 November 2012,
      we searched Web of Science and MEDLINE, without date restrictions, for studies
      describing clinical and non-clinical facility-based SRH prevention and care
      services for FSWs in low- and middle-income countries in Africa. We also
      identified articles in key non-indexed journals and on websites of international
      organizations. A single reviewer screened titles and abstracts, and extracted
      data from articles using standardised tools. RESULTS: We located 149 articles,
      which described 54 projects. Most were localised and small-scale; focused on
      research activities (rather than on large-scale service delivery); operated with
      little coordination, either nationally or regionally; and had scanty government
      support (instead a range of international donors generally funded services).
      Almost all sites only addressed HIV prevention and STIs. Most services
      distributed male condoms, but only 10% provided female condoms. HIV services
      mainly encompassed HIV counselling and testing; few offered HIV care and
      treatment such as CD4 testing or antiretroviral therapy (ART). While STI services
      were more comprehensive, periodic presumptive treatment was only provided in 11
      instances. Services often ignored broader SRH needs such as family planning,
      cervical cancer screening, and gender-based violence services. CONCLUSIONS: Sex
      work programmes in Africa have limited coverage and a narrow scope of services
      and are poorly coordinated with broader HIV and SRH services. To improve FSWs'
      health and reduce onward HIV transmission, access to ART needs to be addressed
      urgently. Nevertheless, HIV prevention should remain the mainstay of services.
      Service delivery models that integrate broader SRH services and address
      structural risk factors are much needed. Government-led FSW services of high
      quality and scale would markedly reduce SRH vulnerabilities of FSWs in Africa.

PMID- 24916012
TI  - Comparison of two food record-based dietary assessment methods for a pan-European
      food consumption survey among infants, toddlers, and children using data quality
      indicators.
AB  - PURPOSE: We aimed (1) to describe and evaluate the "EPIC-Soft DataEntry"
      application developed as a user-friendly data entry tool for pan-European and
      national food consumption surveys among infants and children, and (2) to compare
      two food record-based dietary assessment methods in terms of food description and
      quantification using data quality indicators. EPIC-Soft DataEntry was used for
      both methods. METHODS: Two pilot studies were performed in both Belgium and Czech
      Republic in a total of 376 children (3 months to 10 year olds): one using a
      consecutive 3-day food diary; and the second with two non-consecutive 1-day food
      diaries with data entry during a completion interview. The collected dietary data
      were compared between the two dietary assessment methods by country and by age
      groups: (i) <1 year; (ii) 1-3 years; (iii) >3-10 years. RESULTS: Overall, 70% of
      the interviewers evaluated the work with EPIC-Soft DataEntry as easy. With both
      dietary assessment methods, an equally high proportion of specific food names
      (e.g., "yoghurt, strawberry") were reported, where only between 5 and 15% of
      foods were non-specified (e.g., "yoghurt, n.s."). The two 1-day food diaries
      yielded a higher proportion of foods with detailed description. For example, in
      the age category of 1-3 year olds in Belgium, for 7 out of 16 systematic
      questions on food description (e.g., "preservation method,") specific answers
      were significantly higher (all P < 0.03). The proportion of missing quantities of
      consumed foods was comparable between the two methods. CONCLUSIONS: The EPIC-Soft
      DataEntry application was positively evaluated by the majority of the
      interviewers. Two non-consecutive 1-day food diaries with data entry during a
      completion interview provide a more detailed description of consumed foods as
      compared with a 3-day food diary.

PMID- 24916014
TI  - Experimental and theoretical investigations of the self-association of
      oxaliplatin.
AB  - Self-aggregation in water of anti-cancer agents such as oxaliplatin (1) or its
      palladium-containing parent (2) is suspected to be the main reason for the
      exceptional resistance of concentrated infusions of these complexes to
      hydrolysis; this hypothesis, i.e. the self-association of metal chelates, was
      investigated in a systematic manner by experimental and theoretical means. (1)H
      diffusion-ordered NMR spectroscopy (DOSY NMR) and UV-visible absorption titration
      were inconclusive as to the formation of a dimer of 1 in water or DMSO. Further
      isothermal titration calorimetry (ITC) methods allowed the accurate determination
      of the enthalpy of formation of only the homodimer [2]2 and putative heterodimer
      [1.2] together with an estimation of the formation constants, which indicate that
      dimer formation is not a spontaneous process in solution, whereas electrospray
      ESI mass spectroscopy tends to suggest the contrary in the gas phase. A
      dispersion-corrected DFT method, i.e. DFT-D (BLYP-D3), was used to model the
      aggregation in solution (COSMO) and to investigate the assisting role of London
      force in the cohesion of bimolecular aggregates. The concordance of experimental
      and theoretical thermodynamic parameters was judged reasonably even though the
      treatment of solvation by conventional continuum models does not account for
      specific interactions of the solute with molecules of solvent; nonetheless these
      results outline the importance of dispersion, a.k.a. London force. The role of
      the latter was further stressed by computing the affinities of 1 and 2 for the
      lipophilic cavity of cucurbit[7]uril in modeled water (COSMO-RS), which were
      preliminarily determined experimentally by ITC methods using pure water as
      solvent. From our investigations carried out in pure water the connection between
      the notorious chemical stability of "concentrated" infusions of 1 in aqueous
      media and the formation of oligomers remains unsettled.

PMID- 24916013
TI  - Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double
      blind randomized controlled trial in healthy Chinese elderly.
AB  - PURPOSE: We investigated whether daily supplementation with low-dose B vitamins
      in the healthy elderly population improves the Framingham risk score (FRS), a
      predictor of cardiovascular disease risk. METHODS: Between 2007 and 2012, a
      double-blind randomized controlled trial was conducted in a rural area of North
      China. In all, 390 healthy participants aged 60-74 were randomly allocated to
      receive daily vitamin C (50 mg; control group) or vitamin C plus B vitamins (400
      ug folic acid, 2 mg B6, and 10 ug B12; treatment group) for 12 months. FRSs were
      calculated for all 390 subjects. RESULTS: Folate and vitamin B12 plasma
      concentrations in the treatment group increased by 253 and 80%, respectively,
      after 6 months, stopped increasing with continued supplementation after 12 months
      and returned to baseline levels 6 months after supplementation cessation.
      Compared with the control group, there was no significant effect of B vitamin
      supplementation on FRSs after 6 months (mean difference -0.38; 95% CI -1.06,
      0.31; p = 0.279), whereas a significant effect of supplementation was evident
      after 12 months (reduced magnitude 7.6%; -0.77; 95% CI -1.47, -0.06; p = 0.033).
      However, this reduction disappeared 6 months after supplementation stopped (
      0.07; 95% CI -0.80, 0.66; p = 0.855). The reduction in FRS 12 months after
      supplementation was more pronounced in individuals with a folate deficiency
      (10.4%; -1.30; 95% CI -2.54, -0.07; p = 0.039) than in those without (4.1%; 
      0.38; 95% CI -1.12, 0.36; p = 0.313). B vitamins increased high-density
      lipoprotein cholesterol by 3.4% after 6 months (0.04; 95% CI -0.02, 0.10; p =
      0.155) and by 9.2% after 12 months (0.11; 95 % CI 0.04, 0.18; p = 0.003).
      Compared with the control group, this change in magnitude decreased to 3.3%
      (0.04; 95 % CI -0.02, 0.10; p = 0.194) 6 months after supplementation cessation.
      CONCLUSIONS: Daily supplementation with a low-dose of B vitamins for 12 months
      reduced FRS, particularly in healthy elderly subjects with a folate deficiency.
      These reduced effects declined after supplementation cessation, indicating a need
      for persistent supplementation to maintain the associated benefits.

PMID- 24916015
TI  - Corneal dystrophy-causing SLC4A11 mutants: suitability for folding-correction
      therapy.
AB  - SLC4A11 mutations cause some cases of the corneal endothelial dystrophies,
      congenital hereditary endothelial corneal dystrophy type 2 (CHED2), Harboyan
      syndrome (HS), and Fuchs endothelial corneal dystrophy (FECD). SLC4A11 protein
      was recently identified as facilitating water flux across membranes. SLC4A11
      point mutations usually cause SLC4A11 misfolding and retention in the endoplasmic
      reticulum (ER). We set about to test the feasibility of rescuing misfolded
      SLC4A11 protein to the plasma membrane as a therapeutic approach. Using a
      transfected HEK293 cell model, we measured functional activity present in cells
      expressing SLC4A11 variants in combinations representing the state found in CHED2
      carriers, affected CHED2, FECD individuals, and unaffected individuals. These
      cells manifest respectively about 60%, 5%, and 25% of the water flux activity,
      relative to the unaffected (WT alone). ER-retained CHED2 mutant SLC4A11 protein
      could be rescued to the plasma membrane, where it conferred 25%-30% of WT water
      flux level. Further, some ER-retained CHED2 mutants expressed at 30 degrees C
      supported increased water flux compared with 37 degrees C cultures. Caspase
      activation and cell vitality assays revealed that expression of SLC4A11 mutants
      in HEK293 cells does not induce cell death. We conclude that therapeutics able to
      increase cell surface localization of ER-retained SLC4A11 mutants hold promise to
      treat CHED2 and FECD patients. 

PMID- 24916016
TI  - NMR spectroscopic characterization of new nonsymmetrical bispyridinium choline
      kinase inhibitors.

PMID- 24916018
TI  - Epistaxis caused by a dural AV-fistula at the cribriform plate.
AB  - OBJECTIVES/HYPOTHESIS: A dural arteriovenous fistula (DAVF) with cortical venous
      reflux (CVR) is a dangerous neurovascular entity. A DAVF at the cribriform plate
      is typically silent until its inevitable presentation with intracranial
      hemorrhage. CASE SUMMARY: A 67-year-old male presented with severe epistaxis.
      Following unsuccessful conventional measures and a surgical exploration, a
      catheter angiography showed a DAVF at the cribriform plate, with its nidus
      extending into the nasal cavity. The DAVF was treated via a small craniotomy.
      CONCLUSION: In case of atypical or unexplained nosebleeds, the possibility of a
      DAVF or other neurovascular pathology should be excluded by MRI/MRA or catheter
      angiography.

PMID- 24916019
TI  - Riboswitches based on kissing complexes for the detection of small ligands.
AB  - Biosensors derived from aptamers were designed for which folding into a hairpin
      shape is triggered by binding of the cognate ligand. These aptamers (termed
      aptaswitches) thus switch between folded and unfolded states in the presence and
      absence of the ligand, respectively. The apical loop of the folded aptaswitch is
      recognized by a second hairpin called the aptakiss through loop-loop or kissing
      interactions, whereas the aptakiss does not bind the unfolded aptaswitch.
      Therefore, the formation of a kissing complex signals the presence of the ligand.
      Aptaswitches were designed that enable the detection of GTP and adenosine in a
      specific and quantitative manner by surface plasmon resonance when using a
      grafted aptakiss or in solution by anisotropy measurement with a fluorescently
      labeled aptakiss. This approach is generic and can potentially be extended to the
      detection of any molecule for which hairpin aptamers have been identified, as
      long as the apical loop is not involved in ligand binding. 

PMID- 24916017
TI  - ROSics: chemistry and proteomics of cysteine modifications in redox biology.
AB  - Post-translational modifications (PTMs) occurring in proteins determine their
      functions and regulations. Proteomic tools are available to identify PTMs and
      have proved invaluable to expanding the inventory of these tools of nature that
      hold the keys to biological processes. Cysteine (Cys), the least abundant (1-2%)
      of amino acid residues, are unique in that they play key roles in maintaining
      stability of protein structure, participating in active sites of enzymes,
      regulating protein function and binding to metals, among others. Cys residues are
      major targets of reactive oxygen species (ROS), which are important mediators and
      modulators of various biological processes. It is therefore necessary to identify
      the Cys-containing ROS target proteins, as well as the sites and species of their
      PTMs. Cutting edge proteomic tools which have helped identify the PTMs at
      reactive Cys residues, have also revealed that Cys residues are modified in
      numerous ways. These modifications include formation of disulfide, thiosulfinate
      and thiosulfonate, oxidation to sulfenic, sulfinic, sulfonic acids and
      thiosulfonic acid, transformation to dehydroalanine (DHA) and serine,
      palmitoylation and farnesylation, formation of chemical adducts with glutathione,
      4-hydroxynonenal and 15-deoxy PGJ2, and various other chemicals. We present here,
      a review of relevant ROS biology, possible chemical reactions of Cys residues and
      details of the proteomic strategies employed for rapid, efficient and sensitive
      identification of diverse and novel PTMs involving reactive Cys residues of redox
      sensitive proteins. We propose a new name, "ROSics," for the science which
      describes the principles of mode of action of ROS at molecular levels.

PMID- 24916020
TI  - Reduction of suture associated inflammation after 28 days using novel
      biocompatible pseudoprotein poly(ester amide) biomaterials.
AB  - Sutures elicit an inflammatory response, which may impede the healing process and
      result in wound complications. We recently reported a novel family of
      biocompatible, biodegradable polymers, amino acid-based poly(ester amide)s (AA
      PEA), which we have shown to significantly attenuate the foreign body
      inflammatory response in vitro. Two types of AA-PEA (Phe-PEA and Arg-Phe-PEA)
      were used to coat silk or plain-gut sutures, which were implanted in the gluteus
      muscle of C57BL/6 mice, while the uncoated control sutures were implanted in the
      contralateral side. After 3, 7, 14, and 28 days the mean area of inflammation
      surrounding the sutures was compared. Phe-PEA coating of silk sutures
      significantly decreased inflammation compared with noncoated controls (67.8 +/-
      17.4% after 3d [p = 0.0014], 51.6 +/- 7.2% after 7d [p < 0.001], and 37.3 +/-
      8.3% after 28d [p = 0.0001]) when assessed via analysis of photomicrographs using
      digital image software. Phe-PEA coated plain-gut sutures were similarly assessed
      and demonstrated a significant decrease in the mean area of inflammation across
      all time points (54.1 +/- 8.3% after 3 d, 41.4 +/- 3.9% after 7 d, 71.5 +/- 8.1%
      after 14 d, 78.4 +/- 8.5%, and after 28 d [all p < 0.0001]). Arg-Phe-PEA coated
      silk demonstrated significantly less inflammation compared to noncoated controls
      (61.3 +/- 9.4% after 3 d, 44.7 +/- 4.7% after 7 d, 19.6 +/- 8%, and 38.3 +/- 6.8%
      after 28 d [all p < 0.0001]), as did coated plain-gut (37.4 +/- 8.3% after 3 d [p
      = 0.0004], 55.0 +/- 7.8% after 7 d [p < 0.0001], 46.0 +/- 4.6% after 14 d [p <
      0.0001], and 59.0 +/- 7.9% after 28 d [p < 0.0001]). Both Phe-PEA and Arg-Phe-PEA
      coatings significantly decrease the inflammatory response to sutures in vivo for
      up to 28 days.

PMID- 24916021
TI  - Reply to letter by Cristobal et al.

PMID- 24916022
TI  - Investigation into the effects of varying frequency of mechanical stimulation in
      a cycle-by-cycle manner on engineered cardiac construct function.
AB  - Mechanical stimulation has been used extensively to improve the function of
      cardiac engineered tissue, as it mimics the physical environment in which the
      tissue is situated during normal development. However, previous mechanical
      stimulation has been carried out under a constant frequency that more closely
      resembles a diseased heart. The goal of this study was to create a bioreactor
      system that would allow us to control the mechanical stimulation of engineered
      cardiac tissue on a cycle-by-cycle basis. This unique system allows us to
      determine the effects on cardiac construct function of introducing variability to
      the mechanical stretch. To test our bioreactor system, constructs created from
      neonatal rat cardiomyocytes entrapped in fibrin hydrogels were stimulated under
      various regimes for 2 weeks and then assessed for functional outcomes. No
      differences were observed in the final cell number in each condition, indicating
      that variability in frequency did not have a negative effect on viability. The
      forces were higher for all mechanical stimulation groups compared to static
      controls, although no differences were observed between the mechanically
      stimulated conditions, indicating that variable frequency on a cycle-by-cycle
      basis has limited effects on the resulting force. Although differences in the
      observed twitch force were not observed, differences in the protein expression
      indicate that variable-frequency mechanical stimulation had an effect on cell
      cell coupling and growth pathway activation in the constructs. Thus, this
      bioreactor system provides a valuable tool for further development and
      optimization of engineered myocardial tissue as a repair or replacement strategy
      for patients undergoing heart failure. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24916023
TI  - Sex differences in the association between smoking and abdominal aortic aneurysm.
AB  - BACKGROUND: It is unclear whether recommendations about ultrasound screening
      programmes for abdominal aortic aneurysm (AAA) among men should be extended to
      include women who smoke. The aim was to examine sex-specific dose-response
      associations between AAA risk and smoking status, pack-years smoked and time
      since smoking cessation. METHODS: Women in the Swedish Mammography Cohort and men
      in the Cohort of Swedish Men were followed up from 1998 to 2011. AAA was
      identified through linkage of the cohorts to the Swedish Inpatient Register and
      the Swedish National Register for Vascular Surgery (Swedvasc), and not through
      general ultrasound screening. Associations were estimated with Cox proportional
      hazards models. RESULTS: The cohorts included 35 550 women and 42 596 men, aged
      46-84 years. During follow-up, AAA was identified in 199 women and 958 men. The
      incidence of AAA per 100 000 person-years was 76 among men who never smoked and
      136 among women who currently smoke. Regarding AAA risk, women were more
      sensitive to current smoking (Pinteraction = 0.002). Compared with never smokers,
      the hazard ratio (HR) for AAA in current smokers with more than 20 pack-years was
      10.97 (95 per cent confidence interval 7.41 to 16.26) among women and 6.55 (5.36
      to 7.99) among men. Following smoking cessation, women had a more rapid decline
      in excess risk (Pinteraction < 0.001). The risk was halved after 11 years (HR
      0.51, 0.32 to 0.81) among women and after 23 years (HR 0.50, 0.42 to 0.60) among
      men. CONCLUSION: There were sex differences in the associations between smoking
      status and AAA risk. These data support further investigation of targeted AAA
      screening among women who smoke.

PMID- 24916024
TI  - Additive effects in the palladium-catalyzed carboiodination of chiral N-allyl
      carboxamides.
AB  - The use of Pd catalysis as a means to synthesize organic halides has recently
      received increased attention. Among the reported methods is the Pd-catalyzed
      carboiodination, which uses extremely bulky ligands to facilitate carbon-halogen
      reductive elimination from Pd(II) as the key catalytic step. When approaching
      substrates exhibiting low stereoselectivity, catalyst troubleshooting becomes
      difficult as there are few ligands known to promote the key reductive
      elimination. Herein, we present our finding that tertiary amines act as weakly
      coordinating ligands which significantly enhance diastereoselectivity in the
      Pd/QPhos-catalyzed carboiodination of chiral N-allyl carboxamides. This
      methodology allows efficient access to enantioenriched and densely functionalized
      dihydroisoquinolinones, and has been applied toward the asymmetric formal
      synthesis of (+)-corynoline. 

PMID- 24916025
TI  - Electrophoretic fingerprinting of benzodiazepine tablets in spike drinks.
AB  - Over the last few years, there has been an increase in the reports of drug
      facilitated crimes. The list of drugs associated with these crimes is extensive
      and benzodiazepines constitute one of the groups of substances more commonly
      used. The sedative properties, which characterize benzodiazepines, are enhanced
      when such drugs are combined with alcohol, being more attractive for committing
      these types of crimes. In this work, a capillary electrophoresis method was
      applied to the analysis of 63 different samples of club drinks spiked with
      benzodiazepine tablets. The resulting electropherograms were processed and
      analyzed with the chemometric multivariate techniques: principal component
      analysis (PCA) and soft independent modeling of class analogies (SIMCA)
      classification. The PCA results allowed a clear differentiation of each drug
      class in a 3D plot. In addition, the SIMCA classification model (5% significance
      level) showed that eight out of nine test samples were automatically assigned by
      software to their proper sample class. The conflicting sample was correctly
      classified in the Coomans' plot (95% confidence). This novel approach based on
      the comparison of electrophoretic profiles of spiked drinks by chemometric tools
      allows determining the benzodiazepine used for drink spiking without the use of
      drug standards. Moreover, it provides an opportunity for the forensic
      laboratories to incorporate the identification capability provided by the
      electrophoretic fingerprinting of benzodiazepine solutions in existing or new
      databases. 

PMID- 24916026
TI  - Enhancement of Runx2 expression is potentially linked to beta-catenin
      accumulation in canine intervertebral disc degeneration.
AB  - Intervertebral disc degeneration (IVDD) greatly affects the quality of life. The
      nucleus pulposus (NP) of chondrodystrophic dog breeds (CDBs) is similar to the
      human NP because the cells disappear with age and are replaced by
      fibrochondrocyte-like cells. Because IVDD develops as early as within the first
      year of life, we used canines as a model to investigate the in vitro mechanisms
      underlying IVDD. The mechanism underlying age-related IVDD, however, is poorly
      understood. Several research groups have suggested that Wnt/beta-catenin
      signaling plays an important role in IVDD. However, the role of Wnt/beta-catenin
      signals in IVD cells is not yet well understood. Here, we demonstrate that
      Wnt/beta-catenin signaling could enhance Runx2 expression in IVDD and lead to IVD
      calcification. Nucleus pulposus (NP) tissue was obtained from Beagle dogs after
      evaluation of the degeneration based on magnetic resonance imaging (MRI).
      Histological analysis showed that lack of Safranin-O staining, calcified area,
      and matrix metalloproteinase (MMP) 13-positive cells increased with progression
      of the degeneration. Furthermore, the levels of beta-catenin- and Runx2-positive
      cells also increased. Real-time reverse-transcription polymerase chain reaction
      analysis showed that the MRI signal intensity and mRNA expression levels of beta
      catenin and Runx2 are correlated in NP tissues. Moreover, supplementation of LiCl
      induced beta-catenin accumulation and Runx2 expression. In contrast, FH535
      inhibited LiCl-induced upregulation. These results suggest that Runx2 transcript
      and protein expression, potentially in combination with beta-catenin
      accumulation, are enhanced in degenerated and calcified intervertebral discs of
      CDBs.

PMID- 24916027
TI  - Toxicity of hiba oil constituents and spray formulations to American house dust
      mites and copra mites.
AB  - BACKGROUND: Dermatophagoides farinae and Tyrophagus putrescentiae are recognised
      as an important source of allergens. An assessment was made of the toxicity of
      hiba, Thujopsis dolabrata var. hondai, oil and 13 organic compounds and the
      control efficacy of four experimental spray formulations containing the oil (5-30
      g L(-1) spray) against both mite species. RESULTS: In a contact + fumigant
      mortality bioassay, (-)-thujopsene was the most toxic constituent against D.
      farinae and T. putrescentiae (24 h LC50 9.82 and 10.92 ug cm(-2)), and the
      toxicity of the compound was nearly identical to that of benzyl benzoate (9.33
      and 10.14 ug cm(-2)). The toxicity was more pronounced in carvacrol, (+)-terpinen
      4-ol, beta-thujaplicin, (-)-terpinen-4-ol, cedrol and alpha-terpineol (LC50 12.05
      15.20 and 12.74-16.48 ug cm(-2)) than in N,N-diethyl-3-methylbenzamide (LC50
      35.53 and 38.42 ug cm(-2)) against both mite species. The hiba oil 30 g L(-1)
      spray and commercial permethrin (cis:trans 25:75) 2.5 g L(-1) spray treatment
      resulted in 100 and 11% mortality against the two mite species respectively. In
      vapour-phase mortality tests, the two compounds were consistently more toxic in
      closed versus open containers, indicating that toxicity was achieved mainly
      through the action of vapour. CONCLUSION: Reasonable mite control in indoor
      environments can be achieved by a spray formulation containing the 30 g L(-1)
      hiba oil as a potential contact-action fumigant.

PMID- 24916028
TI  - Design, synthesis and biological evaluation of (E)-3-(3,4
      dihydroxyphenyl)acrylylpiperazine derivatives as a new class of tubulin
      polymerization inhibitors.
AB  - A series of novel (E)-3-(3,4-dihydroxyphenyl)acrylylpiperazine derivatives had
      been synthesized and evaluated their biological activities as potential tubulin
      polymerization inhibitors. Among these compounds, compound 3q exhibited potent
      antiproliferative activities against three cancer cell lines in vitro, and
      antitubulin polymerization activity with IC50 of 0.92 MUM, which was superior to
      that of colchicine (IC50=1.34 MUM). Docking simulation was performed to insert
      compound 3q into the crystal structure of tubulin at colchicine binding site to
      determine the probable binding model. These results suggested that compound 3q
      may be a promising antitubulin agent for the potential treatment of cancer.

PMID- 24916029
TI  - Synthesis and structure-activity relationships of new carbonyl guanidine
      derivatives as novel dual 5-HT2B and 5-HT7 receptor antagonists. Part 2.
AB  - We previously reported that the novel dual 5-HT2B and 5-HT7 receptor antagonist N
      (9-hydroxy-9H-fluorene-2-carbonyl)guanidine (4) exerted a suppressing effect on 5
      HT-induced dural protein extravasation in guinea pigs. To develop a synthetic
      strategy, we performed docking studies of lead compound 4 bound to 5-HT2B and 5
      HT7 receptors, and observed that the carbonyl guanidine group forms a tight
      interaction network with an active center Asp (D135:5-HT2B, D162:5-HT7), Tyr
      (Y370:5-HT2B, Y374:5-HT7) and aromatic residue (W131:5-HT2B, F158:5-HT7). Based
      on molecular modeling results, we optimized the substituents at the 5- to 8
      position and 9-position of the fluorene ring and identified N-(diaminomethylene)
      9-hydroxy-9-methyl-9H-fluorene-2-carboxamide (24a) exhibits potent affinity for 5
      HT2B (Ki=4.3 nM) and 5-HT7 receptor (Ki=4.3 nM) with high selectivity over 5
      HT2A, 5-HT2C, alpha1, D2 and M1 receptors. Compound 24a reversed the hypothermic
      effect of 5-carboxamidotryptamine (5-CT) in mice and also showed a suppressing
      effect on 5-HT-induced dural protein extravasation in guinea pigs when orally
      administered at 30 mg/kg. Compound 24a is therefore a promising candidate for a
      novel class of anti-migraine agent without any adverse effects.

PMID- 24916031
TI  - Neanderthal origin of the haplotypes carrying the functional variant Val92Met in
      the MC1R in modern humans.
AB  - Skin color is one of the most visible and important phenotypes of modern humans.
      Melanocyte-stimulating hormone and its receptor played an important role in
      regulating skin color. In this article, we present evidence of Neanderthal
      introgression encompassing the melanocyte-stimulating hormone receptor gene MC1R.
      The haplotypes from Neanderthal introgression diverged with the Altai Neanderthal
      103.3 ka, which postdates the anatomically modern human-Neanderthal divergence.
      We further discovered that all of the putative Neanderthal introgressive
      haplotypes carry the Val92Met variant, a loss-of-function variant in MC1R that is
      associated with multiple dermatological traits including skin color and
      photoaging. Frequency of this Neanderthal introgression is low in Europeans
      (~5%), moderate in continental East Asians (~30%), and high in Taiwanese
      aborigines (60-70%). As the putative Neanderthal introgressive haplotypes carry a
      loss-of-function variant that could alter the function of MC1R and is associated
      with multiple traits related to skin color, we speculate that the Neanderthal
      introgression may have played an important role in the local adaptation of
      Eurasians to sunlight intensity. 

PMID- 24916032
TI  - Evolutionary origin and human-specific expansion of a cancer/testis antigen gene
      family.
AB  - Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly
      expressed in a number of human cancers. Interestingly, CT antigens are frequently
      involved in gene families that are highly expressed in germ cells. Here, we
      presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma
      associated antigen) gene family to delineate its molecular history and functional
      significance during primate evolution. Comparisons among human, chimpanzee,
      gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate
      specific expansion of CTAGE family, which starts with an ancestral retroposition
      in the haplorhini ancestor. Subsequent DNA-based duplications lead to the
      prosperity of single-exon CTAGE copies in catarrhines, especially in humans.
      Positive selection was identified on the single-exon copies in comparison with
      functional constraint on the multiexon copies. Further sequence analysis suggests
      that the newly derived CTAGE genes may obtain regulatory elements from long
      terminal repeats. Our result indicates the dynamic evolution of primate genomes,
      and the recent expansion of this CT antigen family in humans may confer
      advantageous phenotypic traits during early human evolution. 

PMID- 24916033
TI  - The conversion of PN-junction influencing the piezoelectric output of a CuO/ZnO
      nanoarray nanogenerator and its application as a room-temperature self-powered
      active H2S sensor.
AB  - Room-temperature, high H2S sensing has been realized from a CuO/ZnO nanoarray
      self-powered, active gas sensor. The piezoelectric output of CuO/ZnO nanoarrays
      can act not only as the power source of the device, but also as the H2S sensing
      signal at room temperature. Upon exposure to 800 ppm H2S at room temperature, the
      piezoelectric output of the device greatly decreased from 0.738 V (in air) to
      0.101 V. The sensitivity increased to 629.8, much higher than bare ZnO
      nanoarrays. As the device was exposed to H2S, a CuO/ZnO PN-junction was converted
      into a CuS/ZnO Ohmic contact, which greatly increased the electron density in the
      nanowire and enhanced the screen effect on the piezoelectric output. Our results
      can stimulate a research trend on designing new composite piezoelectric material
      for high-performance self-powered active gas sensors. 

PMID- 24916030
TI  - Evolutionary origins of human herpes simplex viruses 1 and 2.
AB  - Herpesviruses have been infecting and codiverging with their vertebrate hosts for
      hundreds of millions of years. The primate simplex viruses exemplify this pattern
      of virus-host codivergence, at a minimum, as far back as the most recent common
      ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only
      primate species known to be infected with two distinct herpes simplex viruses:
      HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two
      thirds of the human population infected by at least one virus. Here, we
      investigated whether the additional human simplex virus is the result of ancient
      viral lineage duplication or cross-species transmission. We found that standard
      phylogenetic models of nucleotide substitution are inadequate for distinguishing
      among these competing hypotheses; the extent of synonymous substitutions causes a
      substantial underestimation of the lengths of some of the branches in the
      phylogeny, consistent with observations in other viruses (e.g., avian influenza,
      Ebola, and coronaviruses). To more accurately estimate ancient viral divergence
      times, we applied a branch-site random effects likelihood model of molecular
      evolution that allows the strength of natural selection to vary across both the
      viral phylogeny and the gene alignment. This selection-informed model favored a
      scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose
      from a cross-species transmission event from the ancestor of modern chimpanzees
      to an extinct Homo precursor of modern humans, around 1.6 Ma. These results
      provide a new framework for understanding human herpes simplex virus evolution
      and demonstrate the importance of using selection-informed models of sequence
      evolution when investigating viral origin hypotheses. 

PMID- 24916034
TI  - Placental blood flow disappears coincident with a fall in human chorionic
      gonadotropin to undetectable levels in conservative management of placenta
      accreta.

PMID- 24916035
TI  - Chronic pain and suicide: understanding the association.
AB  - Chronic pain conditions are associated with an elevated risk for suicide. Of
      particular importance is the question of why pain conditions might be linked to
      increased suicide risk. We discuss the association between chronic pain and
      psychological pain, particularly in the context of depression, and the use of
      suicide as an attempt to escape from what is perceived as unbearable suffering.
      We also consider the role that chronic pain may play in increasing the capacity
      for suicide. Bridging across research areas and drawing on the interpersonal
      psychological theory of suicide, we suggest that chronic pain may facilitate the
      development of a key risk factor for suicide: fearlessness about death. Given
      that chronic pain can lead to (and be exacerbated by) depression, engender
      hopelessness, facilitate a desire for escape through death, and erode the natural
      fear of dying, clinicians must be aware of psychological processes that can
      combine to create elevated suicide risk in patients with chronic pain, and they
      should also assess and treat suicide risk factors in these patients. 

PMID- 24916036
TI  - Gray matter volume in relation to cardio-vascular stiffness.
AB  - BACKGROUND: Hemodynamic disturbances are associated with aging as well as the
      chronic process of left ventricular and arterial stiffening. This process can
      influence gray matter volume and thereby contribute to brain atrophy. We
      performed a comprehensive assessment of left ventricular and arterial function as
      well as central hemodynamics. These data were correlated with gray matter volume
      (GMV) as evaluated by magnetic resonance imaging (MRI). METHODS: GMV and aortic
      stiffness were estimated using MRI. Left ventricular end-systolic elastance or
      stiffness (Ees), arterial elastance (Ea) and total arterial compliance (TAC) were
      determined by echocardiography. Central hemodynamics were assessed using pulse
      wave analysis. RESULTS: Seventy-five healthy subjects (42 women, 33 men, mean age
      of 58 years) were recruited. The clinical analyses showed that GMV correlates
      significantly and inversely with age (r=-0.37, P=0.001), end-systolic LV
      stiffness (r=-0.39, P=0.0009), augmentation pressure (r=-0.48, P<0.0001),
      arterial elastance (r=-0.27, P=0.02) and aortic stiffness (r=-0.23, P=0.04), as
      determined by aortic pulse wave velocity (aPWV). GMV correlated significantly
      with total arterial compliance (r=0.23, P=0.04). Stepwise forward multiple
      regression analysis revealed that 35% of variance (P<0.0001) in GMV is attributed
      to aPWV, Ees and AP. CONCLUSIONS: Left ventricular end-systolic stiffness,
      augmentation of central arterial pressure and aortic stiffness are associated
      independently and negatively with GMV. These associations suggested that brain
      atrophy is influenced by hemodynamic factors.

PMID- 24916037
TI  - Overweight and obese adults have low intentions of seeking weight-related care: a
      cross-sectional survey.
AB  - BACKGROUND: The prevalence of obesity is growing worldwide. Obesity guidelines
      recommend increasing the level of weight-related care for persons with elevated
      levels of weight-related health risk (WRHR). However, there seems to be a
      discrepancy between need for and use of weight-related care. The primary aim of
      this study is to examine predisposing factors that may influence readiness to
      lose weight and intention to use weight-related care in an overweight population.
      METHODS: A population-based, cross-sectional survey was conducted. Data were
      collected using an online self-administered questionnaire sent to a population
      representative sample of 1,500 Dutch adults on the Health Care Consumer Panel (n
      = 861 responded). Data were used from individuals (n = 445) with a mildly,
      moderately or severely elevated level of WRHR. WRHR status was based on self
      reported data on Body Mass Index, risk assessment for diabetes mellitus type 2
      (DM2) and cardiovascular disease (CVD), or co-morbidities. RESULTS: 55.1% of
      persons with increased WRHR were ready to lose weight (n = 245). Depending on
      level of WRHR; educational level, marital status, individuals with an accurate
      perception of their weight and better perceptions and expectations of dietitians
      were significantly related to readiness to lose weight. Most of them preferred
      individual weight-loss methods (82.0% of n = 245). 11% (n = 26 of n = 245)
      intended to use weight-related care. Weight-related care seeking was higher for
      those with moderate or severe WRHR. Expectations and trust in dietitians did not
      seem to influence care seeking. CONCLUSIONS: Many Dutch adults who are medically
      in need of weight-related care are ready to lose weight. Most intend to lose
      weight individually, and only a few intend to use weight-related care. Therefore,
      obesity prevention initiatives should focus on monitoring weight change and
      weight-loss plans, and timely referral to obesity management. However, many
      people are not ready to lose weight. For this group, strategies for behaviour
      change may depend on WRHR, perceptions of weight and dietitians, educational
      level and marital status. Obesity prevention initiatives should focus on
      increasing the awareness of the seriousness of their condition and offering
      individually appropriate weight management programmes.

PMID- 24916038
TI  - Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy
      in advanced pancreatic cancer.
AB  - Second-line chemotherapy in patients with gemcitabine-refractory advanced
      pancreatic cancer has shown disappointing survival outcomes due to rapid disease
      progression and performance deterioration. The aim of this phase II trial was to
      evaluate the efficacy and safety of adoptive immunotherapy using ex vivo
      expanded, cytokine-induced killer (CIK) cells in gemcitabine-refractory advanced
      pancreatic cancer. Patients with advanced pancreatic cancer who showed disease
      progression during gemcitabine-based chemotherapy were enrolled in this study.
      For generation of CIK cells, peripheral blood samples were collected from each
      patient and cultured with anti-CD3 monoclonal antibody and IL-2. Patients
      received CIK cells intravenously 10 times, every week for 5 weeks and then every
      other week for 10 weeks. Twenty patients were enrolled between November 2009 and
      September 2010. The disease control rate was 25 % (4/16 patients). The median
      progression-free survival (PFS) was 11.0 weeks (95 % CI 8.8-13.2), and the median
      overall survival (OS) was 26.6 weeks (95 % CI 8.6-44.6). Grade 3 toxicities
      included general weakness in two patients and thrombocytopenia in one patient.
      Grade 4 hematologic or non-hematologic toxicity was not observed. Patients showed
      improvement in pancreatic pain, gastrointestinal distress, jaundice, body image
      alterations, altered bowel habits, health satisfaction, and sexuality when
      assessing quality of life (QoL). Adoptive immunotherapy using CIK cells showed
      comparable PFS and OS to survival data of previous trials that assessed
      conventional chemotherapies while maintaining tolerability and showing
      encouraging results in terms of patient QoL in gemcitabine-refractory advanced
      pancreatic cancer (clinicalTrials.gov number NCT00965718). 

PMID- 24916039
TI  - Osteoarthritic cartilage explants affect extracellular matrix production and
      composition in cocultured bone marrow-derived mesenchymal stem cells and
      articular chondrocytes.
AB  - INTRODUCTION: In the present study, we established a novel in vitro coculture
      model to evaluate the influence of osteoarthritis (OA) cartilage explants on the
      composition of newly produced matrix and chondrogenic differentiation of human
      bone marrow-derived mesenchymal stem cells (BMSCs) and the phenotype of OA
      chondrocytes. In addition, we included a "tri-culture" model, whereby a mixture
      of BMSCs and chondrocytes was cultured on the surface of OA cartilage explants.
      METHODS: Gene expression analysis, protein and glycosaminoglycan (GAG) assays,
      dot-blot, immunofluorescence, and biomechanical tests were used to characterize
      the properties of newly generated extracellular matrix (ECM) from chondrocytes
      and chondrogenically differentiated BMSCs and a mix thereof. We compared
      articular cartilage explant cocultures with BMSCs, chondrocytes, and mixed
      cultures (chondrocytes and BMSCs 1:1) embedded in fibrin gels with fibrin gel
      embedded cells cultured without cartilage explants (monocultures). RESULTS: In
      general, co- and tri-cultured cell regimens exhibited reduced mRNA and protein
      levels of collagens I, II, III, and X in comparison with monocultures, whereas no
      changes in GAG synthesis were observed. All co- and tri-culture regimens tended
      to exhibit lower Young's and equilibrium modulus compared with monocultures. In
      contrast, aggregate modulus and hydraulic permeability seemed to be higher in co-
      and tri-cultures. Supernatants of cocultures contained significant higher levels
      of interleukin-1 beta (IL-1beta), IL-6, and IL-8. Stimulation of monocultures
      with IL-1beta and IL-6 reduced collagen gene expression in BMSCs and mixed
      cultures in general but was often upregulated in chondrocytes at late culture
      time points. IL-8 stimulation affected BMSCs only. CONCLUSIONS: Our results
      suggest an inhibitory effect of OA cartilage on the production of collagens. This
      indicates a distinct modulatory influence that affects the collagen composition
      of the de novo-produced ECM from co- and tri-cultured cells and leads to impaired
      mechanical and biochemical properties of the matrix because of an altered
      fibrillar network. We suggest that soluble factors, including IL-1beta and IL-6,
      released from OA cartilage partly mediate these effects. Thus, neighbored OA
      cartilage provides inhibitory signals with respect to BMSCs' chondrogenic
      differentiation and matrix composition, which need to be accounted for in future
      cell-based OA treatment strategies.

PMID- 24916040
TI  - Upregulation of miR-23b enhances the autologous therapeutic potential for
      degenerative arthritis by targeting PRKACB in synovial fluid-derived mesenchymal
      stem cells from patients.
AB  - The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from
      patients with degenerative arthropathy may serve as an alternative therapeutic
      strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of
      OA and RA patients, autologous transplantation of differentiated MSCs has several
      beneficial effects for cartilage regeneration including immunomodulatory
      activity. In this study, we induced chondrogenic differentiation of SFMSCs by
      inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA).
      Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using
      probes specific for aggrecan, the major cartilaginous proteoglycan gene.
      Absorbance of alcian blue stain to detect chondrogenic differentiation was
      increased in H-89 and/or miRNA-23btransfected cells. Furthermore, expression of
      matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated cells.
      Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA
      signaling may be a therapeutic option for OA or RA patients. 

PMID- 24916041
TI  - Mode of neonatal death in an Irish maternity centre.
AB  - Modes of neonatal dying vary among maternity centres, both within and between
      countries. There have been few reports concerning mode of dying from countries
      with low rates of termination of pregnancy, such as Ireland. We conducted a
      retrospective chart review of all neonatal deaths, between January 2010 and
      January 2013, within a single Irish maternity centre. The mode of dying was
      classified as one of (1) withholding life-sustaining treatment (LST), (2)
      withdrawal of LST in moribund infants, (3) withdrawal of LST for quality of life
      reasons or (4) death despite maximal intensive care treatment. There were a total
      of 64 deaths during the study period. Congenital abnormalities accounted for 47 %
      of deaths and prematurity for 41 % of deaths. Withholding LST was the most
      frequent mode of dying, occurring in 38 % of all deaths. A total of 12 % of
      neonatal deaths occurred despite maximal intensive care treatment. CONCLUSIONS:
      Congenital abnormalities were the most common cause of neonatal deaths. A high
      proportion followed LST being withheld, most likely a reflection of the low rates
      of medical termination in Ireland. Modes of dying in the neonatal period vary
      between maternity centres with culturally different backgrounds.